PMID- 26413479
TI - Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion
tractography study.
AB - BACKGROUND: Our understanding of the effect of ataxia-telangiectasia mutated gene
mutations on brain structure and function is limited. In this study, white matter
motor pathway integrity was investigated in ataxia telangiectasia patients using
diffusion MRI and probabilistic tractography. METHODS: Diffusion MRI were
obtained from 12 patients (age range: 7-22 years, mean: 12 years) and 12
typically developing age matched participants (age range 8-23 years, mean: 13
years). White matter fiber tracking and whole tract statistical analyses were
used to assess quantitative fractional anisotropy and mean diffusivity
differences along the cortico-ponto-cerebellar, cerebellar-thalamo-cortical,
somatosensory and lateral corticospinal tract length in patients using a linear
mixed effects model. White matter tract streamline number and apparent fiber
density in patient and control tracts were also assessed. RESULTS: Reduced
fractional anisotropy along all analyzed patient tracts were observed (p <
0.001). Mean diffusivity was significantly elevated in anterior tract locations
but was reduced within cerebellar peduncle regions of all patient tracts (p <
0.001). Reduced tract streamline number and tract volume in the left and right
corticospinal and somatosensory tracts were observed in patients (p < 0.006). In
addition, reduced apparent fiber density in the left and right corticospinal and
right somatosensory tracts (p < 0.006) occurred in patients. CONCLUSIONS: Whole
tract analysis of the corticomotor, corticospinal and somatosensory pathways in
ataxia telangiectasia showed significant white matter degeneration along the
entire length of motor circuits, highlighting that ataxia-telangiectasia gene
mutation impacts the cerebellum and multiple other motor circuits in young
patients.
PMID- 26413480
TI - Transcriptome profiling of sleeping, waking, and sleep deprived adult
heterozygous Aldh1L1 - eGFP-L10a mice.
AB - Transcriptomic studies revealed that hundreds of mRNAs show differential
expression in the brains of sleeping relative to awake rats, mice, flies, and
sparrows. Although these results have offered clues regarding the molecular
consequences of sleep and sleep loss, their functional significance thus far has
been limited. This is probably because the previous studies pooled transcripts
from all brain cells, including neurons and glia. In Bellesi et al. 2015 [1], we
used the translating ribosome affinity purification technology (TRAP) and
microarray analysis to obtain a genome-wide mRNA profiling of astrocytes as a
function of sleep and wake. We used bacterial artificial chromosome (BAC)
transgenic mice expressing eGFP tagged ribosomal protein L10a under the promoter
of the Aldh1L1 gene, a highly expressed astrocytic gene. Using this approach, we
could extract only the astrocytic mRNAs, and only those already committed to be
translated into proteins (L10a is part of the translational machinery). Here, we
report a detailed description of the protocol used in the study [1]. Array data
have been submitted to NCBI GEO under accession number (GSE69079).
PMID- 26413481
TI - Endocrine hypertension: An overview on the current etiopathogenesis and
management options.
AB - Endocrine causes of secondary hypertension include primary aldosteronism,
pheochromocytoma, cushing's syndrome, hyperparathyroidism and hypo- and
hyperthyroidism. They comprise of the 5%-10% of the causes of secondary
hypertension. Primary hyperaldosteronism, the most common of the endocrine cause
of hypertension often presents with resistant or difficult to control
hypertension associated with either normo-or hypokalemia. Pheochromocytoma, the
great mimicker of many conditions, is associated with high morbidity and
mortality if left untreated. A complete history including pertinent family
history, physical examination along with a high index of suspicion with focused
biochemical and radiological evaluation is important to diagnose and effectively
treat these conditions. The cost effective targeted genetic screening for current
known mutations associated with pheochromocytoma are important for early
diagnosis and management in family members. The current review focuses on the
most recent evidence regarding causes, clinical features, methods of diagnosis,
and management of these conditions. A multidisciplinary approach involving
internists, endocrinologists and surgeons is recommended in optimal management of
these conditions.
PMID- 26413482
TI - Hepatocyte selection medium eliminating induced pluripotent stem cells among
primary human hepatocytes.
AB - Hepatic insufficiency is a fatal liver disease with a significant decrease in
functioning hepatocytes. If hepatocytes could be generated from human induced
pluripotent stem (hiPS) cells and transplanted into patients with hepatic
insufficiency, the disease may become curable. However, a major limitation to
this therapeutic strategy is due to the tumorigenicity of hiPS cells and their
ability to form cancer. Current methods for eliminating unwanted hiPS cells use
genetic manipulation or reagents that are potentially hazardous for hepatocytes;
therefore, revised methods are necessary and anticipated. Glucose and arginine
are essential cell culture medium ingredients for the survival of most cells,
including hiPS cells. However, hepatocytes can produce its own glucose and
arginine through galactokinase and ornithine transcarbamylase, respectively.
Therefore, it was hypothesized that unwanted hiPS cells could be eliminated in a
medium without glucose and arginine, and supplemented with galactose and
ornithine instead. This modified medium has been established as hepatocyte
selection medium (HSM). So far, attempts to generate a pure colony of mature
hepatocytes from hiPS cells have not been successful. After establishment of co
culture in HSM, primary human hepatocytes survive while hiPS cells die within
three days. Our latest results regarding a modification of HSM will be introduced
in this manuscript.
PMID- 26413483
TI - Metabolic bone disease in the preterm infant: Current state and future
directions.
AB - Neonatal osteopenia is an important area of interest for neonatologists due to
continuing increased survival of preterm infants. It can occur in high-risk
infants such as preterm infants, infants on long-term diuretics or
corticosteroids, and those with neuromuscular disorders. Complications such as
rickets, pathological fractures, impaired respiratory function and poor growth in
childhood can develop and may be the first clinical evidence of the condition. It
is important for neonatologists managing such high-risk patients to regularly
monitor biochemical markers for evidence of abnormal bone turnover and inadequate
mineral intake in order to detect the early phases of impaired bone
mineralization. Dual-energy X-ray absorptiometry has become an increasingly used
research tool for assessing bone mineral density in children and neonates, but
more studies are still needed before it can be used as a useful clinical tool.
Prevention and early detection of osteopenia are key to the successful management
of this condition and oral phosphate supplements should be started as soon as is
feasible.
PMID- 26413484
TI - Methodological challenges to control for immortal time bias in addressing drug
effects in type 2 diabetes.
AB - There are multiple biases in using observational studies to examine treatment
effects such as those from prevalent drug users, immortal time and drug
indications. We used renin angiotensin system (RAS) inhibitors and statins as
reference drugs with proven efficacies in randomized clinical trials (RCTs) and
examined their effectiveness in the prospective Hong Kong Diabetes Registry using
adjustment methods proposed in the literature. Using time-dependent exposures to
drug treatments yielded greatly inflated hazard ratios (HR) regarding the
treatment effects of these drugs for cardiovascular disease (CVD) in type 2
diabetes. These errors were probably due to changing indications to use these
drugs during follow up periods, especially at the time of drug commencement
making time-dependent analysis extremely problematic. Using time-fixed analysis
with exclusion of immortal time and adjustment for confounders at baseline and/or
during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that
in RCT. The result supported the use of the Registry for performing
pharmacoepidemiological analysis which revealed an attenuated low low-density
lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other
hand, time-fixed analysis with including immortal time and adjustment for
confounders at baseline and/or during follow-up periods, the HR of statins for
CVD was similar to that in the RCT. Our results highlight the complexity and
difficulty in removing these biases. We call for validations of the methods to
cope with immortal time and drug use indications before applying them to
particular research questions, so to avoid making erroneous conclusions.
PMID- 26413485
TI - Endoscopic management of adenomatous ampullary lesions.
AB - Lesions of the ampulla of Vater represent an uncommon group of gastrointestinal
malignancies. The majority of lesions of the ampulla of Vater are either adenomas
or adenocarcinomas. Ampullary lesions are often incidental findings. Accurate
preoperative diagnosis and staging of ampullary tumors is imperative for
predicting prognosis and determining the most appropriate therapeutic approach.
Endoscopic ampullectomy is a safe and efficacious therapeutic procedure that can
obviate the need for potentially major surgical intervention. This review will
provide the framework for the diagnosis and management of ampullary lesions from
the perspective of the practicing gastroenterologist. Strategies for safe and
successful endoscopic ampullectomy with a focus on accurate preoperative
diagnosis and staging, resection technique, and management of complications are
presented.
PMID- 26413486
TI - "How many times must a man look up before he can really see the sky?" Rheumatic
cardiovascular disease in the era of multimodality imaging.
AB - Cardiovascular involvement in rheumatic diseases (RD) is the result of various
pathophysiologic mechanisms including inflammation, accelerated atherosclerosis,
myocardial ischemia, due to micro- or macro-vascular lesions and fibrosis.
Noninvasive cardiovascular imaging, including echocardiography, nuclear
techniques, cardiovascular computed tomography and cardiovascular magnetic
resonance, represents the main diagnostic tool for early, non-invasive diagnosis
of heart disease in RD. However, in the era of multimodality imaging and
financial crisis there is an imperative need for rational use of imaging
techniques in order to obtain the maximum benefit at the lowest possible cost for
the health insurance system. The oligo-asymptomatic cardiovascular presentation
and the high cardiovascular mortality of RD necessitate a reliable and
reproducible diagnostic approach to catch early cardiovascular involvement.
Echocardiography remains the routine cornerstone of cardiovascular evaluation.
However, a normal echocardiogram can not always exclude cardiac involvement
and/or identify heart disease acuity and pathophysiology. Therefore,
cardiovascular magnetic resonance is a necessary adjunct complementary to
echocardiography, especially in new onset heart failure and when there are
conflicting data from clinical, electrocardiographic and echocardiographic
evaluation of RD patients.
PMID- 26413487
TI - Lamb's head: The model for novice education in endoscopic sinus surgery.
AB - Structured training in endonasal endoscopic sinus surgery (EESS) and skull base
surgery is essential considering serious potential complications. We have
developed a detailed concept on training these surgical skills on the lamb's
head. This simple and extremely cheap model offers the possibility of training
even more demanding and advanced procedures in human endonasal endoscopic surgery
such as: frontal sinus surgery, orbital decompression, cerebrospinal fluid-leak
repair followed also by the naso-septal flap, etc. Unfortunately, the sphenoid
sinus surgery cannot be practiced since quadrupeds do not have this sinus. Still,
despite this anatomical limitation, it seems that the lamb's head can be very
useful even for the surgeons already practicing EESS, but in a limited edition
because of a lack of the experience and dexterity. Only after gaining the
essential surgical skills of this demanding field it makes sense to go for the
expensive trainings on the human cadaveric model.
PMID- 26413488
TI - Refractory chronic cough due to gastroesophageal reflux: Definition, mechanism
and management.
AB - Refractory chronic cough due to gastroesophageal reflux is a troublesome
condition unresponsive to the standard medical anti-reflux therapy. Its
underlying mechanisms may include incomplete acid suppression, non-acid reflux,
transient lower esophageal sphincter relaxations and esophageal hypersensitivity.
The diagnosis of this disorder depends on both the findings of multi-channel
intraluminal impedance-pH monitoring and the subsequent intensified anti-reflux
therapy. The strategies of pharmacological treatment for refractory chronic cough
due to reflux include the optimization of proton pump inhibitors and add-on
therapies with histamine H2 receptor antagonists, baclofen and gabapentin.
However, the further study is needed to satisfy its management.
PMID- 26413489
TI - Early probiotics to prevent childhood metabolic syndrome: A systematic review.
AB - AIM: To conduct a systematic review of studies on early probiotic supplementation
to prevent childhood metabolic syndrome (MS). METHODS: Using the Cochrane
systematic review strategy we searched PubMed, EMBASE, CENTRAL, CINAHL, and the
conference proceedings of the Pediatric American Society meetings and trial
registries in December 2014. Randomised controlled trials (RCTs) and non RCTs of
probiotic supplementation to the mother and/or infant for a minimum duration of 4
wk were selected. Of these, studies that reported on MS or its components
(obesity, raised blood pressure, hyperglycemia, dyslipidemia) in children between
2-19 years were to be eligible for inclusion in the review. Risk of bias (ROB) in
selected RCTs and quality assessment of non-RCT studies were to be assessed by
the Cochrane ROB assessment table and New Castle Ottawa scale. RESULTS: There
were no studies on early probiotic administration for prevention of childhood MS
(CMS). Follow up studies of two placebo controlled RCTs (n = 233) reported on the
effects of early probiotics on one or more components of MS in children aged 2-19
years. Meta-analysis of those two studies could not be performed due to
differences in the patient population, type of outcomes studied and the timing of
their assessment. Assessment of childhood metabolic outcomes was not the primary
objective of these studies. The first study that assessed the effects of prenatal
and postnatal supplementation of Lactobacillus rhamnosus GG on body mass index
till 10 years, did not report a significant benefit. In the second study,
Lactobacillus paracasei 19 was supplemented to healthy term infants from 4-13 mo.
No significant effect on body mass index, body composition or metabolic markers
was detected. CONCLUSION: Current evidence on early probiotic administration to
prevent CMS is inadequate. Gaps in knowledge need to be addressed before large
RCTs can be planned.
PMID- 26413491
TI - Aspirin as Primary Prevention of Acute Coronary Heart Disease Events.
AB - BACKGROUND/OBJECTIVE: Aspirin for primary prophylaxis is controversial. This
study evaluated associations between prophylactic aspirin use and incident acute
coronary heart disease (CHD) events. METHODS AND RESULTS: The Reasons for
Geographic and Racial Differences in Stroke (REGARDS) Study was accessed for
aspirin use examining black and white hazards for incident CHD, for men and
women, each adjusting incrementally for sampling, sociodemographics, and CHD risk
factors. Stratified models examined risks across strata of the Framingham risk
score, and all-cause mortality. 23,949 participants (mean 64 yo), had 503
incident events over a 3.5 year follow-up. Prophylactic aspirin use was not
associated with incident acute CHD, HR 1.05 (95% CI 0.86, 1.29). Modeling had
little impact on the HR (1.09 {95% CI 0.89, 1.33) nor did the addition of risk
factors (HR 1.00 {95% CI 0.81, 1.23). Aspirin use was not associated with
incident CHD for any Framingham risk level. Findings were similar when including
all aspirin users (not just those taking aspirin prophylactically), and when
examining associations with all-cause mortality. There was no excess hospitalized
bleeding in the aspirin users. CONCLUSION: Aspirin was not associated with lower
risk for incident acute CHD overall, or within race, gender, or Framingham Risk
Score.
PMID- 26413490
TI - Prevalence of antibiotic resistance in Helicobacter pylori: A recent literature
review.
AB - AIM: To review previous studies (the last 6 years) about the Helicobacter pylori
(H. pylori) antibiotic resistance in order to evaluate the trend in antibiotic
resistance. METHODS: In this study, the PubMed, MEDLINE, Science Direct, Google
Scholar and Scielo manuscripts were reviewed from 2009 to 2014. RESULTS: On the
whole rates of H. pylori antibiotic resistance were 47.22% (30.5%-75.02%) for
metronidazole, 19.74% (5.46%-30.8%) for clarithromycin, 18.94% (14.19%-25.28%)
for levofloxacin, and 14.67% (2%-40.87%) for amoxicillin, 11.70% (0%-50%) for
tetracycline, 11.5% (0%-23%) for furazolidon and 6.75% (1%-12.45%) for rifabutin.
The frequency of tetracycline, metronidazole and amoxicillin resistance was
higher in Africa, while clarithromycin and levofloxacin resistance was higher in
North America and Asian, respectively. CONCLUSION: The most sensitive drug is
rifabutin and the lowest sensitive drug is metronidazole in the world. The
worldwide H. pylori antibiotic resistance to clarithromycin and levofloxacin has
increased during the last 6 years. The present systematic review show alarming
results and a novel plan is needed for eradication therapy of H. pylori
infections.
PMID- 26413492
TI - Effect of spent turmeric on kidney glycoconjugates in streptozotocin-induced
diabetic rats.
AB - BACKGROUND: Curcumin known to have number of medicinal use and masked the fiber
containing ukonan like active polysaccharide in turmeric and its pharmacological
effect will be addressed on diabetic nephropathy particularly the glycoconjugates
of extracellular components viz., glycoproteins and glycosaminoglycans - heparan
sulfate (HS). METHODS: Male Wistar rats were maintained on AIN-76 diet containing
10% spent turmeric and were grouped into control and STZ induced diabetes SFC/TFC
and SFD/TFD, respectively. Diabetic status was monitored using blood and urine,
and at the end, harvested kidneys were used to study the amelioration of
glycoprotiens (collagen) and HS by enzymatic digestion, spectrophotometric,
hydroxyproline and agarose electrophoretic methods. RESULTS: In the present study
spent turmeric (10%) fed diabetic rats showed improved glomerular filtration rate
(50%), kidney enlargement (60%) and other glycoconjugate metabolism in kidney.
Increased collagen content in diabetic group was observed by hydroxyproline
estimation (24%) and periodic acid-Schiff's (PAS) staining. Furthermore, elevated
activities of enzymes involved in the synthesis and degradation of
glycosaminoglycans (GAGs) were significantly lowered in spent turmeric fed
diabetic group. Improvement in total GAGs (43%) and sulfate content (18%)
followed by fractionation of GAGs using specific enzymes led to HS (28%) in the
spent turmeric fed diabetic group, when compared to starch fed diabetic group and
was further confirmed by electrophoresis of GAG. CONCLUSION: These results
clearly indicate beneficial role of spent turmeric in controlling glycoconjugates
such as glycoproteins and heparan sulfate related kidney complications during
diabetes.
PMID- 26413493
TI - Effects of CoQ10 Supplementation on Lipid Profiles and Glycemic Control in
Patients with Type 2 Diabetes: a randomized, double blind, placebo-controlled
trial.
AB - BACKGROUND: Low grade inflammation and oxidative stress are the key factors in
the pathogenesis and development of diabetes and its complications. Coenzyme Q10
(CoQ10) is known as an antioxidant and has a vital role in generation of cellular
energy providing. This study was undertaken to evaluate the effects of CoQ10
supplementation on lipid profiles and glycemic controls in patients with
diabetes. METHODS: Fifty patients with diabetes were randomly allocated into two
groups to receive either 150 mg CoQ10 or placebo daily for 12 weeks. Before and
after supplementation, fasting venous blood samples were collected and lipid
profiles containing triglyceride, total cholesterol, low-density lipoprotein
cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) and glycemic
indices comprising of fasting plasma glucose (FPG), insulin and hemoglobin A1C
(HbA1C) were measured. Insulin resistance was calculated using HOMA-IR index.
RESULTS: Forty patients completed the study. After intervention FPG and HbA1C
were significantly lower in the CoQ10 group compared to the placebo group, but
there were no significant differences in serum insulin and HOMA-IR between the
two groups. Although total cholesterol did not change in the Q10 group after
supplementation, triglyceride and HDL-C significantly decreased and LDL-C
significantly increased in the CoQ10 group. CONCLUSION: The present study showed
that treatment with Q10 may improve glycemic control with no favorable effects on
lipid profiles in type 2 patients with diabetes. TRIAL REGISTRATION: IRCT
registry number: IRCT138806102394N1.
PMID- 26413494
TI - Progress in Treatment Development for Neuropsychiatric Symptoms in Alzheimer's
Disease: Focus on Agitation and Aggression. A Report from the EU/US/CTAD Task
Force.
AB - The management of neuropsychiatric symptoms (NPS) such as agitation and
aggression is a major priority in caring for people with Alzheimer's disease
(AD). Agitation and aggression (A/A) are among the most disruptive symptoms, and
given their impact, they are increasingly an important target for development of
effective treatments. Considerable progress has been made in the last years with
a growing number of randomized controlled trials (RCTs) of drugs for NPS. The
limited benefits reported in some RCTs may be accounted for by the absence of a
biological link of the tested molecule to NPS and also by key methodological
issues. In recent RCTs of A/A, a great heterogeneity design was found. Designing
trials for dementia populations with NPS presents many challenges, including
identification of appropriate participants for such trials, engagement and
compliance of patients and caregivers in the trials and the choice of optimal
outcome measures to demonstrate treatment effectiveness. The EU/US -CTAD Task
Force, an international collaboration of investigators from academia, industry,
non-profit foundations, and regulatory agencies met in Philadelphia on November
19, 2014 to address some of these challenges. Despite potential heterogeneity in
clinical manifestations and neurobiology, agitation and aggression seems to be
accepted as an entity for drug development. The field appears to be reaching a
consensus in using both agitation and aggression (or other NPS)-specific
quantitative measures plus a global rating of change for agitation outcomes based
on clinician judgment as the main outcomes.
PMID- 26413495
TI - Three-dimensional functional unit analysis of hemifacial microsomia mandible-a
preliminary report.
AB - BACKGROUND: The aim of this study was to present three-dimensional (3D)
structural characteristics of the mandible in the hemifacial microsomia. The
mandible has six distinct functional units, and its architecture is the sum of
balanced growth of each functional unit and surrounding matrix. METHODS: In order
to characterize the mandibular 3D architecture of hemifacial microsomia, we
analyzed the mandibular functional units of four hemifacial microsomia patients
using the 3D reconstructed computed tomography (CT) images. And we compared the
functional unit size between affected and non-affected side. RESULTS: The length
of condyle and angle showed significant differences between affected and non
affected sides. However, the length of mandibular body showed insignificant
differences. The size differences between affected and non-affected side were
observed at the condyle, angle, and body in descending order. CONCLUSIONS: This
preliminary study suggests that the main etiopathogenic units are condyle and
angle in the hemifacial microsomia mandible. Further investigation with the
increased number of subjects will be helpful to establish treatment modality by
etiopathogenic targeting of hemifacial microsomia.
PMID- 26413496
TI - Facial asymmetry: a case report of localized linear scleroderma patient with
muscular strain and spasm.
AB - Facial asymmetry is found in patients with or without cosmetic facial
alterations. Some patients have facial asymmetry that manifests underlying
skeletal problems, while others have only limited soft-tissue facial asymmetry.
Orthognathic surgery brings about a dermatic change, as soft tissue covers
underlying bones. Limited soft-tissue asymmetry, meanwhile, is difficult to
correct. The treatment modalities for the creation or restoration of an
esthetically pleasing appearance were autogenous fat grafts, cartilage graft, and
silicon injections. A young female patient had right-side facial asymmetry. The
clinical assessment involved visual inspection of the face and palpation to
differentiate soft tissue and bone. Although the extra-oral examination found
facial asymmetry with skin atrophy, the radiographic findings revealed no
mandibular atrophy or deviation. She was diagnosed as localized scleroderma with
muscle spasm. In conclusion, facial asymmetry patients with skeletal asymmetry
can be esthetically satisfied by orthognathic surgery; however, facial atrophy
patients with skin or subdermal tissue contraction need treatment by cosmetic
dermatological surgery and orthodontic correction.
PMID- 26413497
TI - Assessment of the proximity between the mandibular third molar and inferior
alveolar canal using preoperative 3D-CT to prevent inferior alveolar nerve
damage.
AB - BACKGROUND: The inferior alveolar nerve (IAN) may be injured during extraction of
the mandibular third molar, causing severe postoperative complications. Many
methods have been described for evaluating the relative position between the
mandibular third molar and the inferior alveolar canal (IAC) on panoramic
radiography and computed tomography, but conventional radiography provides
limited information on the proximity of these two structures. The present study
assessed the benefits of three-dimensional computed tomography (3D-CT) prior to
surgical extraction of the mandibular third molar, to prevent IAN damage.
METHODS: This retrospective study included 4917 extractions in 3555 patients who
presented for extraction of the mandibular third molars. The cases were
classified into three groups, according to anatomical relationship between the
mandibular third molars and the IAC on panoramic radiography and whether 3D-CT
was performed. Symptoms of IAN damage were assessed using the touch-recognition
test. Data were compared using the chi-square test and Fisher's exact test.
RESULTS: Among the 32 cases of IAN damage, 6 cases were included in group I (0.35
%, n = 1735 cases), 23 cases in group II (1.1 %, n = 2063 cases), and 3 cases in
group III (0.27 %, n = 1119 cases). The chi-square test showed a significant
difference in the incidence of IAN damage between groups I and II. No significant
difference was observed between groups I and III using Fisher's exact test. In
the 6 cases of IAN damage in group I, the mandibular third molar roots were
located lingual relative to the IAC in 3 cases and middle relative to the IAC in
3 cases. The overlap was >=2 mm in 3 of 6 cases and 0-2 mm in the remaining 3
cases. The mean distance between the mandibular third molar and IAC was 2.2 mm,
the maximum distance 12 mm, and the minimum distance 0.5 mm. Greater than 80 %
recovery was observed in 15 of 32 (46.8 %) cases of IAN damage. CONCLUSIONS: 3D
CT may be a useful tool for assessing the three-dimensional anatomical
relationship and proximity between the mandibular third molar and IAC in order to
prevent IAN damage during extraction of mandibular third molars.
PMID- 26413498
TI - Cannabinoid Receptor Type 2 (CB2) Dependent and Independent Effects of WIN55,212
2 on Atherosclerosis in Ldlr-null Mice.
AB - PURPOSE: WIN55,212-2, a potent synthetic agonist of cannabinoid receptor type 1
(CB1) and cannabinoid receptor type 2 (CB2), reduces atherosclerosis in
apolipoprotein E (ApoE) null mice. Although pharmacologic evidence suggests the
anti-atherosclerotic effects of WIN55,212-2 are mediated via CB2, this remains to
be confirmed by genetic studies. Therefore, in this study, we investigated the
effects of WIN55,212-2 on development of atherosclerosis in low-density
lipoprotein receptor (Ldlr) null mice with and without homozygous deletion of the
CB2 gene. METHODS: After 6 weeks on an atherogenic diet, groups of CB2+/+ and CB2
/- Ldlr-null mice received a daily intraperitoneal injection of WIN55,212-2 or
vehicle. After two weeks, plasma lipid levels and atherosclerosis in the aortic
root were quantified. RESULTS: Plasma cholesterol and triglyceride levels did not
differ between CB2+/+ and CB2-/- mice and WIN55,212-2 had no effect on total
cholesterol levels in either genotype. However, triglyceride levels in both
CB2+/+ and CB2-/- mice were significantly lowered by WIN55,212-2. The size of
aortic root lesions did not differ significantly between CB2+/+ and CB2-/- mice
with or without WIN55,212-2 treatment. However, WIN55,212-2 treatment
significantly lowered lesional macrophage accumulation in CB2+/+ mice, and
lesional smooth muscle content in both CB2+/+ and CB2-/- mice. Lesional apoptosis
was also greater in CB2+/+ mice compared to CB2-/-mice, and only reduced by
WIN55,212-2 in CB2+/+ mice. Collagen content and elastin fiber fragmentation were
unaffected by genotype or WIN55,212-2. CONCLUSIONS: WIN55,212-2 treatment does
not alter lesion size in Ldlr null-mice, but does modify lesion cellularity via
CB2-dependent and CB2-independent mechanisms.
PMID- 26413499
TI - Evaluation of Motor Neuron Excitability by CMAP Scanning with Electric Modulated
Current.
AB - Introduction. Compound Muscle Action Potential (CMAP) scan is a noninvasive
promissory technique for neurodegenerative pathologies diagnosis. In this work
new CMAP scan protocols were implemented to study the influence of electrical
pulse waveform on peripheral nerve excitability. Methods. A total of 13 healthy
subjects were tested. Stimulation was performed with an increasing intensities
range from 4 to 30 mA. The procedure was repeated 4 times per subject, using a
different single pulse stimulation waveform: monophasic square and triangular and
quadratic and biphasic square. Results. Different waveforms elicit different
intensity-response amplitude curves. The square pulse needs less current to
generate the same response amplitude regarding the other waves and this effect is
gradually decreasing for the triangular, quadratic, and biphasic pulse,
respectively. Conclusion. The stimulation waveform has a direct influence on the
stimulus-response slope and consequently on the motoneurons excitability. This
can be a new prognostic parameter for neurodegenerative disorders.
PMID- 26413500
TI - The Effect of Omega-3 Docosahexaenoic Acid Supplementation on Gestational Length:
Randomized Trial of Supplementation Compared to Nutrition Education for
Increasing n-3 Intake from Foods.
AB - OBJECTIVE: DHA supplementation was compared to nutrition education to increase
DHA consumption from fish and DHA fortified foods. DESIGN: This two-part
intervention included a randomized double-blind placebo controlled DHA
supplementation arm and a nutrition education arm designed to increase intake of
DHA from dietary sources by 300 mg per day. SETTING: Denver Health Hospitals and
Clinics, Denver, Colorado, USA. POPULATION: 871 pregnant women aged 18-40 were
recruited between 16 and 20 weeks of gestation of whom 564 completed the study
and complete delivery data was available in 505 women and infants. METHODS:
Subjects received either 300 or 600 mg DHA or olive oil placebo or nutrition
education. MAIN OUTCOME VARIABLE: Gestational length. RESULTS: Gestational length
was significantly increased by 4.0-4.5 days in women supplemented with 600 mg DHA
per day or provided with nutrition education. Each 1% increase in RBC DHA at
delivery was associated with a 1.6-day increase in gestational length. No
significant effects on birth weight, birth length, or head circumference were
demonstrated. The rate of early preterm birth (1.7%) in those supplemented with
DHA (combined 300 and 600 mg/day) was significantly lower than in controls.
CONCLUSION: Nutrition education or supplementation with DHA can be effective in
increasing gestational length.
PMID- 26413501
TI - To Compare Time-Weighted Graphs to Evaluate the Inclination of the Acetabular
Component of Patients Who Had Total Hip Replacement Surgery.
AB - Time-weighted graphs are used to detect small shifts in statistical process
control. The aim of this study is to evaluate the inclination of the acetabular
component with CUmulative SUM (CUSUM) chart, Moving Average (MA) chart, and
Exponentially Weighted Moving Average (EWMA) chart. The data were obtained
directly from thirty patients who had undergone total hip replacement surgery at
Ondokuz Mayis University, Faculty of Medicine. The inclination of the acetabular
component of these people, after total hip replacement, was evaluated. CUSUM
chart, Moving Average chart, and Exponentially Weighted Moving Average were used
to evaluate the quality control process of acetabular component inclination.
MINITAB Statistical Software 15.0 was used to generate these control charts. The
assessment done with time-weighted charts revealed that the acetabular
inclination angles were settled within control limits and the process was under
control. It was determined that the change within the control limits had a random
pattern. As a result of this study it has been obtained that time-weighted
quality control charts which are used mostly in the field of industry can also be
used in the field of medicine. It has provided us with a faster visual decision.
PMID- 26413502
TI - Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents.
AB - Opioids reduce injury from myocardial ischemia-reperfusion in humans. In
experimental models, this mechanism involves GSK3beta inhibition. HSP90 regulates
mitochondrial protein import, with GSK3beta inhibition increasing HSP90
mitochondrial content. Therefore, we determined whether morphine-induced
cardioprotection is mediated by HSP90 and if the protective effect is downstream
of GSK3beta inhibition. Male Sprague-Dawley rats, aged 8-10 weeks, were subjected
to an in vivo myocardial ischemia-reperfusion injury protocol involving 30
minutes of ischemia followed by 2 hours of reperfusion. Hemodynamics were
continually monitored and myocardial infarct size determined. Rats received
morphine (0.3 mg/kg), the GSK3beta inhibitor, SB216763 (0.6 mg/kg), or saline, 10
minutes prior to ischemia. Some rats received selective HSP90 inhibitors,
radicicol (0.3 mg/kg), or deoxyspergualin (DSG, 0.6 mg/kg) alone or 5 minutes
prior to morphine or SB216763. Morphine reduced myocardial infarct size when
compared to control (42 +/- 2% versus 60 +/- 1%). This protection was abolished
by prior treatment of radicicol or DSG (59 +/- 1%, 56 +/- 2%). GSK3beta
inhibition also reduced myocardial infarct size (41 +/- 2%) with HSP90 inhibition
by radicicol or DSG partially inhibiting SB216763-induced infarct size reduction
(54 +/- 3%, 47 +/- 1%, resp.). These data suggest that opioid-induced
cardioprotection is mediated by HSP90. Part of this protection afforded by HSP90
is downstream of GSK3beta, potentially via the HSP-TOM mitochondrial import
pathway.
PMID- 26413503
TI - Compressed Sensing for fMRI: Feasibility Study on the Acceleration of Non-EPI
fMRI at 9.4T.
AB - Conventional functional magnetic resonance imaging (fMRI) technique known as
gradient-recalled echo (GRE) echo-planar imaging (EPI) is sensitive to image
distortion and degradation caused by local magnetic field inhomogeneity at high
magnetic fields. Non-EPI sequences such as spoiled gradient echo and balanced
steady-state free precession (bSSFP) have been proposed as an alternative high
resolution fMRI technique; however, the temporal resolution of these sequences is
lower than the typically used GRE-EPI fMRI. One potential approach to improve the
temporal resolution is to use compressed sensing (CS). In this study, we tested
the feasibility of k-t FOCUSS--one of the high performance CS algorithms for
dynamic MRI--for non-EPI fMRI at 9.4 T using the model of rat somatosensory
stimulation. To optimize the performance of CS reconstruction, different sampling
patterns and k-t FOCUSS variations were investigated. Experimental results show
that an optimized k-t FOCUSS algorithm with acceleration by a factor of 4 works
well for non-EPI fMRI at high field under various statistical criteria, which
confirms that a combination of CS and a non-EPI sequence may be a good solution
for high-resolution fMRI at high fields.
PMID- 26413504
TI - Dentin Morphology of Root Canal Surface: A Quantitative Evaluation Based on a
Scanning Electronic Microscopy Study.
AB - Dentin is a vital, hydrated composite tissue with structural components and
properties that vary in the different topographic portions of the teeth. These
variations have a significant implication for biomechanical teeth properties and
for the adhesive systems utilized in conservative dentistry. The aim of this
study is to analyse the root canal dentin going from coronal to apical zone to
find the ratio between the intertubular dentin area and the surface occupied by
dentin tubules varies. Observations were conducted on 30 healthy premolar teeth
extracted for orthodontic reasons in patients aged between 10 and 14. A SEM
analysis of the data obtained in different canal portions showed that, in the
coronal zone, dentinal tubules had a greater diameter (4.32 MUm) than the middle
zone (3.74 MUm) and the apical zone (1.73 MUm). The average number of dentinal
tubules (in an area of 1 mm(2)) was similar in coronal zone (46,798 +/- 10,644)
and apical zone (45,192 +/- 10,888), while in the middle zone they were lower in
number (30,940 +/- 7,651). However, intertubular dentin area was bigger going
from apical to coronal portion. The differences between the analysed areas must
be considered for the choice of the adhesive system.
PMID- 26413505
TI - Correction for Eddy Current-Induced Echo-Shifting Effect in Partial-Fourier
Diffusion Tensor Imaging.
AB - In most diffusion tensor imaging (DTI) studies, images are acquired with either a
partial-Fourier or a parallel partial-Fourier echo-planar imaging (EPI) sequence,
in order to shorten the echo time and increase the signal-to-noise ratio (SNR).
However, eddy currents induced by the diffusion-sensitizing gradients can often
lead to a shift of the echo in k-space, resulting in three distinct types of
artifacts in partial-Fourier DTI. Here, we present an improved DTI acquisition
and reconstruction scheme, capable of generating high-quality and high-SNR DTI
data without eddy current-induced artifacts. This new scheme consists of three
components, respectively, addressing the three distinct types of artifacts.
First, a k-space energy-anchored DTI sequence is designed to recover eddy current
induced signal loss (i.e., Type 1 artifact). Second, a multischeme partial
Fourier reconstruction is used to eliminate artificial signal elevation (i.e.,
Type 2 artifact) associated with the conventional partial-Fourier reconstruction.
Third, a signal intensity correction is applied to remove artificial signal
modulations due to eddy current-induced erroneous T2(*) -weighting (i.e., Type 3
artifact). These systematic improvements will greatly increase the consistency
and accuracy of DTI measurements, expanding the utility of DTI in translational
applications where quantitative robustness is much needed.
PMID- 26413506
TI - Adjunctive Pessary Therapy after Emergency Cervical Cerclage for Cervical
Insufficiency with Protruding Fetal Membranes in the Second Trimester of
Pregnancy: A Novel Modification of Treatment.
AB - AIM: To evaluate the effectiveness of adjunctive pessary therapy after emergency
cervical cerclage (ECC) in improving perinatal outcome in cervical insufficiency
with fetal membranes protruding into the vagina. MATERIAL AND METHODS: A
retrospective analysis of patients treated at the 1st Department of Obstetrics
and Gynecology, Medical University of Warsaw, between 2008 and 2013. The study
group consisted of 15 women treated with ECC and a pessary and the control group
consisted of 17 patients treated with cerclage only. RESULTS: The mean
gestational age at delivery was significantly higher in the study group (34.7
versus 29.7 weeks, p = 0.03). The period between cerclage insertion and delivery
was significantly longer in the study group (82.9 versus 52.1 days, p = 0.045).
The mean neonatal birthweight and neonatal "discharge alive" ratio were higher in
the study group, although not statistically significant (2550 g versus 1883 g, p
= 0.14, and 93.3% versus 70.5%, p = 0.18, resp.). NICU hospitalization rates were
comparable (33.3% versus 35.3%, p = 0.9). CONCLUSIONS: Adjunctive pessary therapy
allows delaying delivery in women treated with ECC due to cervical insufficiency
with protruding fetal membranes. It also seems to improve neonatal outcome,
although the differences are not statistically significant. Further prospective
study is required to prove these findings.
PMID- 26413507
TI - Automatic Tooth Segmentation of Dental Mesh Based on Harmonic Fields.
AB - An important preprocess in computer-aided orthodontics is to segment teeth from
the dental models accurately, which should involve manual interactions as few as
possible. But fully automatic partition of all teeth is not a trivial task, since
teeth occur in different shapes and their arrangements vary substantially from
one individual to another. The difficulty is exacerbated when severe teeth
malocclusion and crowding problems occur, which is a common occurrence in
clinical cases. Most published methods in this area either are inaccurate or
require lots of manual interactions. Motivated by the state-of-the-art general
mesh segmentation methods that adopted the theory of harmonic field to detect
partition boundaries, this paper proposes a novel, dental-targeted segmentation
framework for dental meshes. With a specially designed weighting scheme and a
strategy of a priori knowledge to guide the assignment of harmonic constraints,
this method can identify teeth partition boundaries effectively. Extensive
experiments and quantitative analysis demonstrate that the proposed method is
able to partition high-quality teeth automatically with robustness and
efficiency.
PMID- 26413508
TI - Epigenomics of Neural Cells: REST-Induced Down- and Upregulation of Gene
Expression in a Two-Clone PC12 Cell Model.
AB - Cell epigenomics depends on the marks released by transcription factors operating
via the assembly of complexes that induce focal changes of DNA and histone
structure. Among these factors is REST, a repressor that, via its strong
decrease, governs both neuronal and neural cell differentiation and specificity.
REST operation on thousands of possible genes can occur directly or via indirect
mechanisms including repression of other factors. In previous studies of gene
down- and upregulation, processes had been only partially investigated in neural
cells. PC12 are well-known neural cells sharing properties with neurons. In the
widely used PC12 populations, low-REST cells coexist with few, spontaneous high
REST PC12 cells. High- and low-REST PC12 clones were employed to investigate the
role and the mechanisms of the repressor action. Among 15,500 expressed genes we
identified 1,770 target and nontarget, REST-dependent genes. Functionally, these
genes were found to operate in many pathways, from synaptic function to
extracellular matrix. Mechanistically, downregulated genes were predominantly
repressed directly by REST; upregulated genes were mostly governed indirectly.
Among other factors, Polycomb complexes cooperated with REST for downregulation,
and Smad3 and Myod1 participated in upregulation. In conclusion, we have
highlighted that PC12 clones are a useful model to investigate REST, opening
opportunities to development of epigenomic investigation.
PMID- 26413509
TI - Resting-State fMRI in MS: General Concepts and Brief Overview of Its Application.
AB - Brain functional connectivity (FC) is defined as the coherence in the activity
between cerebral areas under a task or in the resting-state (RS). By applying
functional magnetic resonance imaging (fMRI), RS FC shows several patterns which
define RS brain networks (RSNs) involved in specific functions, because brain
function is known to depend not only on the activity within individual regions,
but also on the functional interaction of different areas across the whole brain.
Region-of-interest analysis and independent component analysis are the two most
commonly applied methods for RS investigation. Multiple sclerosis (MS) is
characterized by multiple lesions mainly affecting the white matter, determining
both structural and functional disconnection between various areas of the central
nervous system. The study of RS FC in MS is mainly aimed at understanding
alterations in the intrinsic functional architecture of the brain and their role
in disease progression and clinical impairment. In this paper, we will examine
the results obtained by the application of RS fMRI in different multiple
sclerosis (MS) phenotypes and the correlations of FC changes with clinical
features in this pathology. The knowledge of RS FC changes may represent a
substantial step forward in the MS research field, both for clinical and
therapeutic purposes.
PMID- 26413510
TI - Tracking Transplanted Stem Cells Using Magnetic Resonance Imaging and the
Nanoparticle Labeling Method in Urology.
AB - A reliable in vivo imaging method to localize transplanted cells and monitor
their viability would enable a systematic investigation of cell therapy. Most
stem cell transplantation studies have used immunohistological staining, which
does not provide information about the migration of transplanted cells in vivo in
the same host. Molecular imaging visualizes targeted cells in a living host,
which enables determining the biological processes occurring in transplanted stem
cells. Molecular imaging with labeled nanoparticles provides the opportunity to
monitor transplanted cells noninvasively without sacrifice and to repeatedly
evaluate them. Among several molecular imaging techniques, magnetic resonance
imaging (MRI) provides high resolution and sensitivity of transplanted cells. MRI
is a powerful noninvasive imaging modality with excellent image resolution for
studying cellular dynamics. Several types of nanoparticles including
superparamagnetic iron oxide nanoparticles and magnetic nanoparticles have been
used to magnetically label stem cells and monitor viability by MRI in the
urologic field. This review focuses on the current role and limitations of MRI
with labeled nanoparticles for tracking transplanted stem cells in urology.
PMID- 26413511
TI - Evaluation of the Contribution of Signals Originating from Large Blood Vessels to
Signals of Functionally Specific Brain Areas.
AB - The fusiform face area (FFA) is known to play a pivotal role in face processing.
The FFA is located in the ventral region, at the base of the brain, through which
large blood vessels run. The location of the FFA via functional MRI (fMRI) may be
influenced by these large blood vessels. Responses of large blood vessels may not
exactly correspond to neuronal activity in a target area, because they may be
diluted and influenced by inflow effects. In this study, we investigated the
effects of large blood vessels in the FFA, that is, whether the FFA includes
large blood vessels and/or whether inflow signals contribute to fMRI signals of
the FFA. For this purpose, we used susceptibility-weighted imaging (SWI)
sequences to visualize large blood vessels and dual-echo gradient-echo echo
planar imaging (GE-EPI) to measure inflow effects. These results showed that the
location and response signals of the FFA were not influenced by large blood
vessels or inflow effects, although large blood vessels were located near the
FFA. Therefore, the data from the FFA obtained by individual analysis were robust
to large blood vessels but leaving a warning that the data obtained by group
analysis may be prone to large blood vessels.
PMID- 26413512
TI - Tropomyosin and Actin Identified as Major Allergens of the Carpet Clam (Paphia
textile) and the Effect of Cooking on Their Allergenicity.
AB - OBJECTIVES: To identify the major allergenic proteins of clam (Paphia textile)
and to investigate the effect of different cooking methods on the allergenicity
of these identified proteins. METHODS: Clam protein extracts were separated by
denaturing polyacrylamide gel electrophoresis. IgE reactive proteins were then
analyzed by immunoblotting with sera from patients with positive skin prick tests
(SPT) to the raw clam extract. Mass spectrometry was used to identify the major
allergenic proteins of this clam. RESULTS: Raw extract showed 12 protein bands
(18-150 kDa). In contrast, fewer protein bands were seen in the boiled extract;
those ranging from 40 to 150 kDa were denatured. The protein profiles were
similarly altered by frying or roasting. The immunoblots of raw and boiled
extracts yielded 10 and 2 IgE-binding proteins, respectively. The fried and
roasted extracts showed only a single IgE-binding protein at 37 kDa. Mass
spectrometry analysis of the 37 and 42 kDa major allergens indicated that these
spots were tropomyosin and actin, respectively. CONCLUSION: The two major
allergens of Paphia textile were identified as the thermostable tropomyosin and a
new thermolabile allergen actin.
PMID- 26413513
TI - Pretreatment Diffusion-Weighted MRI Can Predict the Response to Neoadjuvant
Chemotherapy in Patients with Nasopharyngeal Carcinoma.
AB - PURPOSE: To explore the potential of diffusion-weighted (DW) magnetic resonance
imaging (MRI) using apparent diffusion coefficient (ADC) for predicting the
response to neoadjuvant chemotherapy in nasopharyngeal carcinoma (NPC). METHODS
AND MATERIALS: Ninety-two consecutive patients with NPC who underwent three
cycles of neoadjuvant chemotherapy were retrospectively analyzed. DW and
anatomical MRI were performed before and after neoadjuvant chemotherapy prior to
radiotherapy. Pretreatment ADCs and percentage increases in ADC after
chemotherapy were calculated for the primary lesions and metastatic adenopathies.
Receiver operating characteristic curve analysis was used to select optimal
pretreatment ADCs. RESULTS: Pretreatment mean ADCs were significantly lower for
responders than for nonresponders (primary lesions, P = 0.012; metastatic
adenopathies, P = 0.013). Mean percentage increases in ADC were higher for
responders than for nonresponders (primary lesions, P = 0.008; metastatic
adenopathies, P < 0.001). The optimal pretreatment primary lesion and metastatic
adenopathy ADCs for differentiating responders from nonresponders were 0.897 *
10(-3) mm(2)/sec and 1.031 * 10(-3) mm(2)/sec, respectively. CONCLUSIONS: NPC
patients with low pretreatment ADCs tend to respond better to neoadjuvant
chemotherapy. Pretreatment ADCs could be used as a new pretreatment imaging
biomarker of response to neoadjuvant chemotherapy.
PMID- 26413514
TI - Epidemiological Scenario of Dengue in Brazil.
AB - Dengue is the most important reemerging mosquito-borne viral disease worldwide.
It is caused by any of four Dengue virus types or serotypes (DENV-1 to DENV-4)
and is transmitted by mosquitoes from the genus Aedes. Ecological changes have
favored the geographic expansion of the vector and, since the dengue pandemic in
the Asian and Pacific regions, the infection became widely distributed worldwide,
reaching Brazil in 1845. The incidence of dengue in Brazil has been frequently
high, and the number of cases in the country has at some point in time
represented up to 60% of the dengue reported cases worldwide. This review
addresses vector distribution, dengue outbreaks, circulating serotypes and
genotypes, and prevention approaches being utilized in Brazil.
PMID- 26413515
TI - Developmental Changes in Morphology of the Middle and Posterior External Cranial
Base in Modern Homo sapiens.
AB - The basicranium has been described as phylogenetically informative,
developmentally stable, and minimally affected by external factors and
consequently plays an important role in cranial size and shape in subadult
humans. Here basicranial variation of subadults from several modern human
populations was investigated and the impact of genetic relatedness on basicranial
morphological similarities was investigated. Three-dimensional landmark data were
digitized from subadult basicrania from seven populations. Published molecular
data on short tandem repeats were statistically compared to morphological data
from three ontogenetic stages. Basicranial and temporal bone morphology both
reflect genetic distances in childhood and adolescence (5-18 years), but not in
infancy (<5 years). The occipital bone reflects genetic distances only in
adolescence (13-18 years). The sphenoid bone does not reflect genetic distances
at any ontogenetic stage but was the most diagnostic region evaluated, resulting
in high rates of correct classification among populations. These results suggest
that the ontogenetic processes driving basicranial development are complex and
cannot be succinctly summarized across populations or basicranial regions.
However, the fact that certain regions reflect genetic distances suggests that
the morphology of these regions may be useful in reconstructing population
history in specimens for which direct DNA evidence is unavailable, such as
archaeological sites.
PMID- 26413516
TI - Functional and Structural Details about the Fabella: What the Important
Stabilizer Looks Like in the Central European Population.
AB - The posterolateral corner of the knee accommodating the fabella complex is of
importance in orthopaedic surgery. Unfortunately, there is a lack of data in
literature for clinical routine. Therefore, we investigated the fabella's
characteristics, biomechanical nature, and present histologic details. Of special
interest were the fabella's occurrence and position, calcium concentration as
long-term load intake indicator, and the histology. Within our analysis, fabellae
were found in 30.0% of all datasets, located on the upper part of the
posterolateral femoral condyle. The region of fabella contact on this condyle
showed a significantly lower calcium concentration than its surroundings.
Histologically, the fabella showed no articular cartilage but a clearly
distinguishable fabellofibular ligament that consisted of two bundles: one, as
already described in literature inserted at the fibular tip, and another part
newly described on the top of the lateral meniscus. In its role of stabilizing
the soft tissue structures of the posterolateral knee, the fabella seems to serve
as suspension for the ligaments evolving from its base. Even though a joint
formation of any kind is unlikely, the presence of a fabella needs to be kept in
mind during knee examination and any surgical procedures.
PMID- 26413517
TI - Quantitative Anatomy of the Growing Lungs in the Human Fetus.
AB - Using anatomical, digital, and statistical methods we examined the three
dimensional growth of the lungs in 67 human fetuses aged 16-25 weeks. The lung
dimensions revealed no sex differences. The transverse and sagittal diameters and
the base circumference were greater in the right lungs while the lengths of
anterior and posterior margins and the lung height were greater in the left
lungs. The best-fit curves for all the lung parameters were natural logarithmic
models. The transverse-to-sagittal diameter ratio remained stable and averaged
0.56 +/- 0.08 and 0.52 +/- 0.08 for the right and left lungs, respectively. For
the right and left lungs, the transverse diameter-to-height ratio significantly
increased from 0.74 +/- 0.09 to 0.92 +/- 0.08 and from 0.56 +/- 0.07 to 0.79 +/-
0.09, respectively. The sagittal diameter-to-height ratio significantly increased
from 1.41 +/- 0.23 to 1.66 +/- 0.18 in the right lung, and from 1.27 +/- 0.17 to
1.48 +/- 0.22 in the left lung. In the fetal lungs, their proportionate increase
in transverse and sagittal diameters considerably accelerates with relation to
the lung height. The lung dimensions in the fetus are relevant in the evaluation
of the normative pulmonary growth and the diagnosis of pulmonary hypoplasia.
PMID- 26413518
TI - Fast Imaging Technique for fMRI: Consecutive Multishot Echo Planar Imaging
Accelerated with GRAPPA Technique.
AB - This study was to evaluate the proposed consecutive multishot echo planar imaging
(cmsEPI) combined with a parallel imaging technique in terms of signal-to-noise
ratio (SNR) and acceleration for a functional imaging study. We developed cmsEPI
sequence using both consecutively acquired multishot EPI segments and variable
flip angles to minimize the delay between segments and to maximize the SNR,
respectively. We also combined cmsEPI with the generalized autocalibrating
partially parallel acquisitions (GRAPPA) method. Temporal SNRs were measured at
different acceleration factors and number of segments for functional sensitivity
evaluation. We also examined the geometric distortions, which inherently occurred
in EPI sequence. The practical acceleration factors, R = 2 or R = 3, of the
proposed technique improved the temporal SNR by maximally 18% in phantom test and
by averagely 8.2% in in vivo experiment, compared to cmsEPI without parallel
imaging. The data collection time was decreased in inverse proportion to the
acceleration factor as well. The improved temporal SNR resulted in better
statistical power when evaluated on the functional response of the brain. In this
study, we demonstrated that the combination of cmsEPI with the parallel imaging
technique could provide the improved functional sensitivity for functional
imaging study, compensating for the lower SNR by cmsEPI.
PMID- 26413519
TI - Anthropometric Measurements Usage in Medical Sciences.
AB - Morphometry is introduced as quantitative approach to seek information concerning
variations and changes in the forms of organisms that described the relationship
between the human body and disease. Scientists of all civilization, who existed
until today, examined the human body using anthropometric methods. For these
reasons, anthropometric data are used in many contexts to screen for or monitor
disease. Anthropometry, a branch of morphometry, is the study of the size and
shape of the components of biological forms and their variations in populations.
Morphometrics can also be defined as the quantitative analysis of biological
forms. The field has developed rapidly over the last two decades to the extent
that we now distinguish between traditional morphometrics and the more recent
geometric morphometrics. Advances in imaging technology have resulted in the
protection of a greater amount of morphological information and have permitted
the analysis of this information. The oldest and most commonly used of these
methods is radiography. With developments in this area, CT and MRI have also been
started to be used in screening of the internal organs. Morphometric measurements
that are used in medicine, are widely used in the diagnosis and the follow-up and
the treatment of the disease, today. In addition, in cosmetology use of these new
measurements is increasing every day.
PMID- 26413520
TI - Preterm Birth: Pathophysiology, Prevention, Diagnosis, and Treatment.
PMID- 26413521
TI - Disease Related Knowledge Summarization Based on Deep Graph Search.
AB - The volume of published biomedical literature on disease related knowledge is
expanding rapidly. Traditional information retrieval (IR) techniques, when
applied to large databases such as PubMed, often return large, unmanageable lists
of citations that do not fulfill the searcher's information needs. In this paper,
we present an approach to automatically construct disease related knowledge
summarization from biomedical literature. In this approach, firstly Kullback
Leibler Divergence combined with mutual information metric is used to extract
disease salient information. Then deep search based on depth first search (DFS)
is applied to find hidden (indirect) relations between biomedical entities.
Finally random walk algorithm is exploited to filter out the weak relations. The
experimental results show that our approach achieves a precision of 60% and a
recall of 61% on salient information extraction for Carcinoma of bladder and
outperforms the method of Combo.
PMID- 26413522
TI - Predictors for Early Identification of Hepatitis C Virus Infection.
AB - Hepatitis C virus (HCV) infection can cause permanent liver damage and
hepatocellular carcinoma, and deaths related to HCV deaths have recently
increased. Chronic HCV infection is often undiagnosed such that the virus remains
infective and transmissible. Identifying HCV infection early is essential for
limiting its spread, but distinguishing individuals who require further HCV tests
is very challenging. Besides identifying high-risk populations, an optimal subset
of indices for routine examination is needed to identify HCV screening
candidates. Therefore, this study analyzed data from 312 randomly chosen blood
donors, including 144 anti-HCV-positive donors and 168 anti-HCV-negative donors.
The HCV viral load in each sample was measured by real-time polymerase chain
reaction method. Receiver operating characteristic curves were used to find the
optimal cell blood counts and thrombopoietin measurements for screening purposes.
Correlations with values for key indices and viral load were also determined.
Strong predictors of HCV infection were found by using receiver operating
characteristics curves to analyze the optimal subsets among red blood cells,
monocytes, platelet counts, platelet large cell ratios, and mean corpuscular
hemoglobin concentrations. Sensitivity, specificity, and area under the receiver
operator characteristic curve (P < 0.0001) were 75.6%, 78.5%, and 0.859,
respectively.
PMID- 26413523
TI - Transarterial Embolization for Hepatocellular Carcinoma: A Comparison between
Nonspherical PVA and Microspheres.
AB - Transarterial chemoembolization (TACE) and transarterial embolization (TAE) have
improved the survival rates of patients with unresectable hepatocellular
carcinoma (HCC); however, the optimal TACE/TAE embolic agent has not yet been
identified. The aim of this study was to compare the effect of two different
embolic agents such as microspheres (ME) and polyvinyl alcohol (PVA) on survival,
tumor response, and complications in patients with HCC submitted to transarterial
embolization (TAE). Eighty HCC patients who underwent TAE between June 2008 and
December 2012 at a single center were retrospectively studied. A total of 48 and
32 patients were treated with PVA and ME, respectively. There were no significant
differences in survival (P = 0.679) or tumoral response (P = 0.369) between
groups (PVA or ME). Overall survival rates at 12, 18, 24, 36, and 48 months were
97.9, 88.8, 78.9, 53.4, and 21.4% in the PVA-TAE group and 100, 92.9, 76.6, 58.8,
and 58% in the ME-TAE group (P = 0.734). Patients submitted to TAE with ME
presented postembolization syndrome more frequently when compared with the PVA
group (P = 0.02). According to our cohort, the choice of ME or PVA as embolizing
agent had no significant impact on overall survival.
PMID- 26413525
TI - Comment on "Transmission Model of Hepatitis B Virus with the Migration Effect".
AB - Some consequences of erroneous results concerning eigenvalues in the recent
literature of mathematical biology are highlighted. Furthermore, an improved
stability criterion and the true value of the basic reproduction number is
presented.
PMID- 26413524
TI - Psychobiobehavioral Model for Preterm Birth in Pregnant Women in Low- and Middle
Income Countries.
AB - Preterm birth (PTB) is a final common outcome resulting from many interrelated
etiological pathways; of particular interest is antenatal psychosocial distress
(i.e., stress, anxiety, and depression). In LMI countries, both exposure to
severe life stressors and rate of PTB are on average greater when compared with
high-income countries. In LMI countries women are exposed to some of the most
extreme psychosocial stress worldwide (e.g., absolute poverty, limited social
resources). High prevalence of antenatal stress and depression have been observed
in some studies from LMI countries. We propose a psychosocial, biological, and
behavioral model for investigating the complex multisystem interactions in stress
responses leading to PTB and explain the basis of this approach. We discuss
ethical considerations for a psychosocial, biological, and behavioral screening
tool to predict PTB from a LMI country perspective.
PMID- 26413526
TI - Lentivirus-Mediated siRNA Targeting ER-alpha Inhibits Tumorigenesis and Induces
Apoptosis in Hepatocarcinoma Cells.
AB - BACKGROUND AND OBJECTIVES: Estrogen receptor-alpha (ER-alpha) plays important
roles in hepatocarcinogenesis. Recent studies have shown that ER-alpha could lead
to cell cycle progression or inhibition of apoptosis. To better understand the
role of ER-alpha, RNA interference (RNAi) was used to inhibit ER-alpha expression
in the human hepatocellular carcinoma (HCC) cells. METHODS: Lentivirus-mediated
ER-alpha small interfering RNA (siRNA) was transfected into HCC cells Hep3B. ER
alpha expression was monitored by real-time polymerase chain reaction (PCR) and
western blot. Cell proliferation, apoptosis, and invasion were examined by methyl
thiazol tetrazolium (MTT), flow cytometry (FCM), and invasion assay,
respectively. RESULTS: ER-alpha siRNA efficiently downregulated the expression of
ER-alpha in Hep3B cells at both mRNA and protein levels in a time-dependent
manner. ER-alpha siRNA also inhibited cell proliferation and reduced cell
invasion (compared with other groups, P < 0.05, resp.). Furthermore, knockdown of
ER-alpha slowed down the cell population at S phase and increased the rate of
apoptosis (P < 0.05, resp.). CONCLUSION: ER-alpha knockdown suppressed the growth
of HCC cells. Thus, ER-alpha may play a very important role in carcinogenesis of
HCC and its knockdown may offer a new potential gene therapy approach for human
liver cancer in the future.
PMID- 26413527
TI - Predict Defibrillation Outcome Using Stepping Increment of Poincare Plot for Out
of-Hospital Ventricular Fibrillation Cardiac Arrest.
AB - Early cardiopulmonary resuscitation together with early defibrillation is a key
point in the chain of survival for cardiac arrest. Optimizing the timing of
defibrillation by predicting the possibility of successful electric shock can
guide treatments between defibrillation and cardiopulmonary resuscitation and
improve the rate of restoration of spontaneous circulation. Numerous methods have
been proposed for predicting defibrillation success based on quantification of
the ventricular fibrillation waveform during past decades. To date, however, no
analytical technique has been widely accepted for clinical application. In the
present study, we investigate whether median stepping increment that is
calculated from the Euclidean distance of consecutive points in Poincare plot
could be used to predict the likelihood of successful defibrillation.
Electrocardiographic recordings of out-of-hospital cardiac arrest patients were
obtained from the external defibrillators. The performance of the proposed method
was evaluated by receiver operating characteristic curve and compared with the
results of other established features. The results indicated that median stepping
increment has comparable performance to the established methods in predicting the
likelihood of successful defibrillation.
PMID- 26413528
TI - MRI for Assessing Response to Neoadjuvant Therapy in Locally Advanced Rectal
Cancer Using DCE-MR and DW-MR Data Sets: A Preliminary Report.
AB - To evaluate MRI for neoadjuvant therapy response assessment in locally advanced
rectal cancer (LARC) using dynamic contrast enhanced-MRI (DCE-MRI) and diffusion
weighted imaging (DWI), we have compared magnetic resonance volumetry based on
DCE-MRI (V(DCE)) and on DWI (V(DWI)) scans with conventional T2-weighted
volumetry (V(C)) in LARC patients after neoadjuvant therapy. Twenty-nine patients
with LARC underwent MR examination before and after neoadjuvant therapy. A manual
segmentation was performed on DCE-MR postcontrast images, on DWI (b-value 800
s/mm(2)), and on conventional T2-weighted images by two radiologists. DCE-MRI,
DWI, and T2-weigthed volumetric changes before and after treatment were
evaluated. Nonparametric sample tests, interobserver agreement, and receiver
operating characteristic curve (ROC) were performed. Diagnostic performance
linked to DCE-MRI volumetric change was superior to T2-w and DW-MRI volumetric
changes performance (specificity 86%, sensitivity 93%, and accuracy 93%). Area
Under ROC (AUC) of V(DCE) was greater than AUCs of V(C) and V(DWI) resulting in
an increase of 15.6% and 11.1%, respectively. Interobserver agreement between two
radiologists was 0.977, 0.864, and 0.756 for V(C), V(DCE), and V(DWI),
respectively. V(DCE) seems to be a promising tool for therapy response assessment
in LARC. Further studies on large series of patients are needed to refine
technique and evaluate its potential value.
PMID- 26413529
TI - Evaluation of Nutritional Status of Patients with Depression.
AB - AIMS AND OBJECTIVES: Our goal was to determine nutritional status, body
composition, and biochemical parameters of patients diagnosed with depression
based on DSM-IV-TR criteria. METHODS: A total of 59 individuals, aged 18-60 years
admitted to Mental Health Centre of Kayseri Education and Research Hospital, were
included in the study. The participants were randomly assigned to two groups;
depression group (n = 29) and control group (n = 30). Anthropometric
measurements, some biochemical parameters, demographic data, and 24-hour dietary
recall were evaluated. RESULTS: 65.5% of depression and 60.0% of control group
were female. Intake of vitamins A, thiamine, riboflavin, B6, folate, C, Na, K,
Mg, Ca, P, Fe, Zn, and fibre (p < 0.05) were lower in depression group. Median
levels of body weight, waist circumference, hip circumference, waist-to-hip ratio
(p < 0.05) were significantly higher in depression group. Fasting blood glucose
levels, serum vitamins B12, and folic acid (p < 0.05) in depression group were
lower than controls. Serum insulin and HOMA levels of two groups were similar.
CONCLUSION: Some vitamin B consumption and serum vitamin B12 and folic acid
levels were low while signs of abdominal obesity were high among patients with
depression. Future research exploring nutritional status of individuals with
depression is warranted.
PMID- 26413530
TI - A Prospective Randomized Study of Brain Tissue Oxygen Pressure-Guided Management
in Moderate and Severe Traumatic Brain Injury Patients.
AB - The purpose of this study was to compare the effect of PbtO2-guided therapy with
traditional intracranial pressure- (ICP-) guided treatment on the management of
cerebral variables, therapeutic interventions, survival rates, and neurological
outcomes of moderate and severe traumatic brain injury (TBI) patients. From 2009
to 2010, TBI patients with a Glasgow coma scale <12 were recruited from 6
collaborative hospitals in northern Taiwan, excluding patients with severe
systemic injuries, fixed and dilated pupils, and other major diseases. In total,
23 patients were treated with PbtO2-guided management (PbtO2 > 20 mmHg), and 27
patients were treated with ICP-guided therapy (ICP < 20 mmHg and CPP > 60 mmHg)
in the neurosurgical intensive care unit (NICU); demographic characteristics were
similar across groups. The survival rate in the PbtO2-guided group was also
significantly increased at 3 and 6 months after injury. Moreover, there was a
significant correlation between the PbtO2 signal and Glasgow outcome scale
extended in patients from 1 to 6 months after injury. This finding demonstrates
that therapy directed by PbtO2 monitoring is valuable for the treatment of
patients with moderate and severe TBI and that increasing PaO2 to 150 mmHg may be
efficacious for preventing cerebral hypoxic events after brain trauma.
PMID- 26413531
TI - A Window into the Brain: Advances in Psychiatric fMRI.
AB - Functional magnetic resonance imaging (fMRI) plays a key role in modern
psychiatric research. It provides a means to assay differences in brain systems
that underlie psychiatric illness, treatment response, and properties of brain
structure and function that convey risk factor for mental diseases. Here we
review recent advances in fMRI methods in general use and progress made in
understanding the neural basis of mental illness. Drawing on concepts and
findings from psychiatric fMRI, we propose that mental illness may not be
associated with abnormalities in specific local regions but rather corresponds to
variation in the overall organization of functional communication throughout the
brain network. Future research may need to integrate neuroimaging information
drawn from different analysis methods and delineate spatial and temporal patterns
of brain responses that are specific to certain types of psychiatric disorders.
PMID- 26413532
TI - Three-Dimensional Assessment of Bilateral Symmetry of the Scaphoid: An Anatomic
Study.
AB - Preoperative 3D CT imaging techniques provide displacement analysis of the distal
scaphoid fragment in 3D space, using the matched opposite scaphoid as reference.
Its accuracy depends on the presence of anatomical bilateral symmetry, which has
not been investigated yet using similar techniques. Our purpose was to
investigate symmetry by comparing the relative positions of distal and proximal
poles between sides. We used bilateral CT scans of 19 adult healthy volunteers to
obtain 3D scaphoid models. Left proximal and distal poles were matched to
corresponding mirrored right sides. The left-to-right positional differences
between poles were quantified in terms of three translational and three
rotational parameters. The mean (SD) of ulnar, dorsal, and distal translational
differences of distal poles relative to proximal poles was 0.1 (0.6); 0.4 (1.2);
0.2 (0.6) mm and that of palmar rotation, ulnar deviation, and pronation
differences was -1.1 (4.9); -1.5 (3.3); 1.0 (3.7) degrees , respectively. These
differences did not significantly differ from zero and thus were not biased to
left or right side. We proved that, on average, the articular surfaces of
scaphoid poles were symmetrically aligned in 3D space. This suggests that the
contralateral scaphoid can serve as reference in corrective surgery. No level of
evidence is available.
PMID- 26413533
TI - Change in the Pathologic Supraspinatus: A Three-Dimensional Model of Fiber Bundle
Architecture within Anterior and Posterior Regions.
AB - Supraspinatus tendon tears are common and lead to changes in the muscle
architecture. To date, these changes have not been investigated for the distinct
regions and parts of the pathologic supraspinatus. The purpose of this study was
to create a novel three-dimensional (3D) model of the muscle architecture
throughout the supraspinatus and to compare the architecture between muscle
regions and parts in relation to tear severity. Twelve cadaveric specimens with
varying degrees of tendon tears were used. Three-dimensional coordinates of fiber
bundles were collected in situ using serial dissection and digitization. Data
were reconstructed and modeled in 3D using Maya. Fiber bundle length (FBL) and
pennation angle (PA) were computed and analyzed. FBL was significantly shorter in
specimens with large retracted tears compared to smaller tears, with the deeper
fibers being significantly shorter than other parts in the anterior region. PA
was significantly greater in specimens with large retracted tears, with the
superficial fibers often demonstrating the largest PA. The posterior region was
absent in two specimens with extensive tears. Architectural changes associated
with tendon tears affect the regions and varying depths of supraspinatus
differently. The results provide important insights on residual function of the
pathologic muscle, and the 3D model includes detailed data that can be used in
future modeling studies.
PMID- 26413534
TI - Preliminary Observations on Sensitivity and Specificity of Magnetization Transfer
Asymmetry for Imaging Myelin of Rat Brain at High Field.
AB - Magnetization transfer ratio (MTR) has been often used for imaging myelination.
Despite its high sensitivity, the specificity of MTR to myelination is not high
because tissues with no myelin such as muscle can also show high MTR. In this
study, we propose a new magnetization transfer (MT) indicator, MT asymmetry
(MTA), as a new method of myelin imaging. The experiments were performed on rat
brain at 9.4 T. MTA revealed high signals in white matter and significantly low
signals in gray matter and muscle, indicating that MTA has higher specificity
than MTR. Demyelination and remyelination studies demonstrated that the
sensitivity of MTA to myelination was as high as that of MTR. These experimental
results indicate that MTA can be a good biomarker for imaging myelination. In
addition, MTA images can be efficiently acquired with an interslice MTA method,
which may accelerate clinical application of myelin imaging.
PMID- 26413535
TI - Effect of Bone Cement Implantation on Haemodynamics in Elderly Patients and
Preventive Measure in Cemented Hemiarthroplasty.
AB - This study was to investigate the influence of bone cement implantation on
haemodynamics and the preventive effect of epinephrine hydrochloride on pulmonary
embolism in elderly patients with cemented semihip replacement. 128 patients were
retrospectively analyzed. The patients were treated with (group A, 64 cases) or
without (group B, 64 cases) epinephrine hydrochloride saline. The monitoring
indicators included systolic blood pressure (SBP), diastolic blood pressure
(DBP), mean arterial pressure (MAP), heart rate (HR), and pulse oxygen saturation
(SPO2). The indicators of the two groups were compared before and 1, 2, 3, 4, 5,
6, 7, 8, 9, and 10 minutes after bone cement implantation. Analysis of variance
and SNK-q test were used for the statistical analysis. Blood pressure and SPO2 of
group B decreased with statistical difference (P < 0.05) and HR increased without
statistical significance, comparing with those of group A. In group A, SBP, DBP,
MAP, HR, and SPO2 after bone cement implantation did not change significantly at
each time point comparing with before implantation (P > 0.05). Bone cement
implantation has significant influence on hemodynamics in elderly patients with
hemiarthroplasty. Flushing the bone marrow cavity with saline epinephrine
hydrochloride is an effective measure to reduce the incidence of bone cement
pulmonary embolism.
PMID- 26413536
TI - Soluble and Endogenous Secretory Receptors for Advanced Glycation End Products in
Threatened Preterm Labor and Preterm Premature Rupture of Fetal Membranes.
AB - The aim of the study was to compare sRAGE and esRAGE plasma levels in pregnant
women with (A) threatened premature labor (n = 41), (B) preterm premature rupture
of membranes (n = 49), and (C) preterm rupture of membranes at term (n = 48). The
relationship between these and classic intrauterine infection markers and the
latent time from symptoms up to delivery depending on RAGE's concentration were
investigated. In groups A and B, a positive correlation was found between plasma
sRAGE and latent time (r = 0,422; p = 0,001; r = 0,413, p = 0,004, resp.). High
prognostic values were found in both groups for plasma sRAGE concentration and
the latent time from symptoms up to delivery. Groups B and C presented higher
levels of esRAGE than group A (526,315 +/- 129,453 pg/mL and 576,212 +/- 136,237
pg/mL versus 485,918 +/- 133,127 pg/mL, p< 0,05). The conclusion is that sRAGE
concentration can be a favorable prognostic factor in the presence of symptoms of
threatened premature labor. Higher esRAGE plasma level in case of the rupture of
membranes in mature and premature pregnancy suggests its participation in fetal
membranes destruction.
PMID- 26413537
TI - MRI Guided Brain Stimulation without the Use of a Neuronavigation System.
AB - A key issue in the field of noninvasive brain stimulation (NIBS) is the accurate
localization of scalp positions that correspond to targeted cortical areas. The
current gold standard is to combine structural and functional brain imaging with
a commercially available "neuronavigation" system. However, neuronavigation
systems are not commonplace outside of specialized research environments. Here we
describe a technique that allows for the use of participant-specific functional
and structural MRI data to guide NIBS without a neuronavigation system. Surface
mesh representations of the head were generated using Brain Voyager and vectors
linking key anatomical landmarks were drawn on the mesh. Our technique was then
used to calculate the precise distances on the scalp corresponding to these
vectors. These calculations were verified using actual measurements of the head
and the technique was used to identify a scalp position corresponding to a brain
area localized using functional MRI.
PMID- 26413538
TI - Volumetric MR-Guided High-Intensity Focused Ultrasound with Direct Skin Cooling
for the Treatment of Symptomatic Uterine Fibroids: Proof-of-Concept Study.
AB - OBJECTIVE: To prospectively assess the safety and technical feasibility of
volumetric magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU)
ablation with direct skin cooling (DISC) during treatment of uterine fibroids.
METHODS: In this proof-of-concept study, eight patients were consecutively
selected for clinical MR-HIFU ablation of uterine fibroids with the use of an
additional DISC device to maintain a constant temperature (T ~ 20 degrees C) at
the interface between the HIFU table top and the skin. Technical feasibility was
verified by successful completion of MR-HIFU ablation. Contrast-enhanced T1
weighted MRI was used to measure the treatment effect (nonperfused volume (NPV)
ratio). Safety was evaluated by recording of adverse events (AEs) within 30 days'
follow-up. RESULTS: All MR-HIFU treatments were successfully completed in an
outpatient setting. The median NPV ratio was 0.56 (IQR [0.27-0.72]). Immediately
after treatment, two patients experienced coldness related discomfort which
resolved at the same day. No serious (device-related) AEs were reported.
Specifically, no skin burns, cold injuries, or subcutaneous edema were observed.
CONCLUSION: This study showed that it is safe and technically feasible to
complete a volumetric MR-HIFU ablation with DISC. This technique may reduce the
risk of thermal injury to the abdominal wall during MR-HIFU ablation of uterine
fibroids. This trial is registered with NTR4189.
PMID- 26413539
TI - Two-Dimensional Crystallization Procedure, from Protein Expression to Sample
Preparation.
AB - Membrane proteins play important roles for living cells. Structural studies of
membrane proteins provide deeper understanding of their mechanisms and further
aid in drug design. As compared to other methods, electron microscopy is uniquely
suitable for analysis of a broad range of specimens, from small proteins to large
complexes. Of various electron microscopic methods, electron crystallography is
particularly well-suited to study membrane proteins which are reconstituted into
two-dimensional crystals in lipid environments. In this review, we discuss the
steps and parameters for obtaining large and well-ordered two-dimensional
crystals. A general description of the principle in each step is provided since
this information can also be applied to other biochemical and biophysical
methods. The examples are taken from our own studies and published results with
related proteins. Our purpose is to give readers a more general idea of electron
crystallography and to share our experiences in obtaining suitable crystals for
data collection.
PMID- 26413540
TI - Morphometric Evaluation of Korean Femurs by Geometric Computation: Comparisons of
the Sex and the Population.
AB - We measured 28 parameters of 202 femurs from Koreans by an automated geometric
computation program using 3D models generated from computed tomography images.
The measurement parameters were selected with reference to physical and forensic
anthropology studies as well as orthopedic implant design studies. All
measurements were calculated using 3D reconstructions on a computer using
scientific computation language. We also analyzed sex and population differences
by comparison with data from previous studies. Most parameters were larger in
males than in females. The height, head diameter, head center offset, and chord
length of the diaphysis, most parameters in the distal femur, and the isthmic
width of the medullary canal were smaller in Koreans than in other populations.
However, the neck-shaft angle, subtense, and width of the intercondylar notch in
the distal femur were larger than those in other populations. The results of this
study will be useful as a reference for physical and forensic anthropology as
well as the design of medical devices suitable for Koreans.
PMID- 26413541
TI - The Association between Endometriomas and Ovarian Cancer: Preventive Effect of
Inhibiting Ovulation and Menstruation during Reproductive Life.
AB - Although endometriosis frequently involves multiple sites in the pelvis,
malignancies associated with this disease are mostly confined to the ovaries,
evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of
transformation in clear-cell, endometrioid, and possibly low-grade serous ovarian
cancers, but not in mucinous ovarian cancers. These last cancers are, in some
aspects, different from the other epithelial ovarian cancers, as they do not
appear to be decreased by the inhibition of ovulation and menstruation. The step
by step process of transformation from typical endometrioma, through atypical
endometrioma, finally to ovarian cancer seems mainly related to oxidative stress,
inflammation, hyperestrogenism, and specific molecular alterations. Particularly,
activation of oncogenic KRAS and PI3K pathways and inactivation of tumor
suppressor genes PTEN and ARID1A are suggested as major pathogenic mechanisms for
endometriosis associated clear-cell and endometrioid ovarian cancer. Both the
risk for endometriomas and their associated ovarian cancers seems to be highly
and similarly decreased by the inhibition of ovulation and retrograde
menstruation, suggesting a common pathogenetic mechanism and common possible
preventive strategies during reproductive life.
PMID- 26413542
TI - Added Value of Assessing Adnexal Masses with Advanced MRI Techniques.
AB - This review will present the added value of perfusion and diffusion MR sequences
to characterize adnexal masses. These two functional MR techniques are readily
available in routine clinical practice. We will describe the acquisition
parameters and a method of analysis to optimize their added value compared with
conventional images. We will then propose a model of interpretation that combines
the anatomical and morphological information from conventional MRI sequences with
the functional information provided by perfusion and diffusion weighted
sequences.
PMID- 26413544
TI - Using Magnetic Resonance for Predicting Femoral Strength: Added Value with
respect to Bone Densitometry.
AB - BACKGROUND AND PURPOSE: To evaluate the added value of MRI with respect to
peripheral quantitative computed tomography (pQCT) and dual energy X-ray
absorptiometry (DXA) for predicting femoral strength. MATERIAL AND METHODS: Bone
mineral density (BMD) of eighteen femur specimens was assessed with pQCT, DXA,
and MRI (using ultrashort echo times (UTE) and the MicroView software).
Subsequently biomechanical testing was performed to assess failure load. Simple
and multiple linear regression were used with failure load as the dependent
variable. RESULTS: Simple linear regression allowed a prediction of failure load
with either pQCT, DXA, or MRI in an r(2) range of 0.41-0.48. Multiple linear
regression with pQCT, DXA, and MRI yielded the best prediction (r(2) = 0.68).
CONCLUSIONS: The accuracy of MRI, using UTE and MicroView software, to predict
femoral strength compares well with that of pQCT or DXA. Furthermore, the
inclusion of MRI in a multiple-regression model yields the best prediction.
PMID- 26413545
TI - Influence of the Weight of a School Backpack on Spinal Curvature in the Sagittal
Plane of Seven-Year-Old Children.
AB - The aim of the paper was to determine a correlation between the weight of a
child's backpack, their body weight, and certain features of their body posture.
MATERIAL AND METHODS: The study group consisted of 109 children, all aged seven
years. The parameters of body posture were determined using the Zebris Ultrasonic
System. RESULTS: The number of children carrying a school backpack in accordance
with recommendations was 44 subjects (40.37%). Statistically significant changes
were found in the total length of the spine (Z = 2.223, p = 0.026) and between
backpack weight and changes in the following parameters: the total length of the
spine (rs = -0.3999, p = 0.017), the length and the angle of the lumbar lordosis
(rs = -0.3352, p = 0.049), the angle of the lumbar lordosis (rs = -0.5065, p =
0.002), and the sacral angle (rs = -0.4279, p = 0.010). CONCLUSIONS: Wearing a
backpack heavier than 10% of one's body weight can cause shallowing of the lumbar
lordosis and a tendency towards a vertical position of the sacrum. Monitoring the
weight of children's school backpacks and enabling them to leave books and
notebooks at school would probably be beneficial in reducing the daily burden put
on children's spines.
PMID- 26413543
TI - MRI for Crohn's Disease: Present and Future.
AB - Crohn's disease (CD) is a chronic inflammatory condition with relapsing-remitting
behavior, often causing strictures or penetrating bowel damage. Its lifelong
clinical course necessitates frequent assessment of disease activity and
complications. Computed tomography (CT) enterography has been used as primary
imaging modality; however, the concern for radiation hazard limits its use
especially in younger population. Magnetic resonance (MR) imaging has advantages
of avoiding radiation exposure, lower incidence of adverse events, ability to
obtain dynamic information, and good soft-tissue resolution. MR enterography
(MRE) with oral contrast agent has been used as primary MR imaging modality of CD
with high sensitivity, specificity, and interobserver agreement. The extent of
inflammation as well as transmural ulcers and fibrostenotic diseases can be
detected with MRE. Novel MR techniques such as diffusion-weighted MRI (DWI),
motility study, PET-MRI, and molecular imaging are currently investigated for
further improvement of diagnosis and management of CD. MR spectroscopy is a
remarkable molecular imaging tool to analyze metabolic profile of CD with human
samples such as plasma, urine, or feces, as well as colonic mucosa itself.
PMID- 26413546
TI - Exploring Dynamic Brain Functional Networks Using Continuous "State-Related"
Functional MRI.
AB - We applied a "temporal decomposition" method, which decomposed a single brain
functional network into several "modes"; each of them dominated a short temporal
period, on a continuous, "state-" related, "finger-force feedback" functional
magnetic resonance imaging experiment. With the hypothesis that attention and
internal/external information processing interaction could be manipulated by
different (real and sham) feedback conditions, we investigated functional network
dynamics of the "default mode," "executive control," and sensorimotor networks.
They were decomposed into several modes. During real feedback, the occurrence of
"default mode-executive control competition-related" mode was higher than that
during sham feedback (P = 0.0003); the "default mode-visual facilitation-related"
mode more frequently appeared during sham than real feedback (P = 0.0004).
However, the dynamics of the sensorimotor network did not change significantly
between two conditions (P > 0.05). Our results indicated that the visual-guided
motor feedback involves higher cognitive functional networks rather than primary
motor network. The dynamics monitoring of inner and outside environment and
multisensory integration could be the mechanisms. This study is an extension of
our previous region-specific and static-styled study of our brain functional
architecture.
PMID- 26413547
TI - How to Quantify Penile Corpus Cavernosum Structures with Histomorphometry:
Comparison of Two Methods.
AB - The use of morphometrical tools in biomedical research permits the accurate
comparison of specimens subjected to different conditions, and the surface
density of structures is commonly used for this purpose. The traditional point
counting method is reliable but time-consuming, with computer-aided methods being
proposed as an alternative. The aim of this study was to compare the surface
density data of penile corpus cavernosum trabecular smooth muscle in different
groups of rats, measured by two observers using the point-counting or color-based
segmentation method. Ten normotensive and 10 hypertensive male rats were used in
this study. Rat penises were processed to obtain smooth muscle immunostained
histological slices and photomicrographs captured for analysis. The smooth muscle
surface density was measured in both groups by two different observers by the
point-counting method and by the color-based segmentation method. Hypertensive
rats showed an increase in smooth muscle surface density by the two methods, and
no difference was found between the results of the two observers. However,
surface density values were higher by the point-counting method. The use of
either method did not influence the final interpretation of the results, and both
proved to have adequate reproducibility. However, as differences were found
between the two methods, results obtained by either method should not be
compared.
PMID- 26413548
TI - Tumour Relapse Prediction Using Multiparametric MR Data Recorded during Follow-Up
of GBM Patients.
AB - PURPOSE: We have focused on finding a classifier that best discriminates between
tumour progression and regression based on multiparametric MR data retrieved from
follow-up GBM patients. MATERIALS AND METHODS: Multiparametric MR data consisting
of conventional and advanced MRI (perfusion, diffusion, and spectroscopy) were
acquired from 29 GBM patients treated with adjuvant therapy after surgery over a
period of several months. A 27-feature vector was built for each time point,
although not all features could be obtained at all time points due to missing
data or quality issues. We tested classifiers using LOPO method on complete and
imputed data. We measure the performance by computing BER for each time point and
wBER for all time points. RESULTS: If we train random forests, LogitBoost, or
RobustBoost on data with complete features, we can differentiate between tumour
progression and regression with 100% accuracy, one time point (i.e., about 1
month) earlier than the date when doctors had put a label (progressive or
responsive) according to established radiological criteria. We obtain the same
result when training the same classifiers solely on complete perfusion data.
CONCLUSIONS: Our findings suggest that ensemble classifiers (i.e., random forests
and boost classifiers) show promising results in predicting tumour progression
earlier than established radiological criteria and should be further
investigated.
PMID- 26413549
TI - Increase in Preterm Birth during Demographic Transition in Chile from 1991 to
2012.
AB - INTRODUCTION: Universally mothers at 35 years or more have had higher maternal
and perinatal risks. This study analyzed the trend of this group in maternal
population and determined their risk of having premature children, during the
demographic transition period in Chile. MATERIALS AND METHODS: Epidemiological
study conducted in the population of simple live births registered in the Chilean
National Database Births of 1991-2012. Analyses were performed in three
categories of maternal age: 35 or more, under 35, and 20 to 29 years. The risk of
prematurity was measured by crude and Adjusted Odds Ratio from logistic
regression model. RESULTS: Mothers aged 35 and older increased in population from
10.6% in 1991 to 16.7% in 2012 and presented an overall prevalence of preterm
delivery of 6.7%, higher prevalence than 20-29 age group (4.7%). In aging
mothers, the Odds Ratio for preterm birth adjusted for education, marital status,
and parity was 1.68 (95% CI (1.66-1.70)) compared to mothers aged 20-29. All
differences were significant (p < 0.001). CONCLUSIONS: During Chilean demographic
transition, mothers aged 35 or older increased steadily and significantly
maintaining higher risks of preterm births. Policies to prevent and monitor the
late motherhood could contribute to stopping the current trend.
PMID- 26413550
TI - Association of Aortic Diameters with Coronary Artery Disease Severity and Albumin
Excretion.
AB - INTRODUCTION: Aortic diameters, aortic distensibility, microalbuminuria, coronary
artery disease which are all together related to vascular aging are investigated
in this paper. METHODS: Eighty consecutive nondiabetic patients undergoing
elective coronary angiography were enrolled into the study. Systolic and
diastolic aortic diameters, aortic distensibility, CAD severity by angiogram with
the use of Gensini scoring, and albumin excretion rates were determined. RESULTS:
Cases with CAD had significantly larger systolic (30,72 +/- 3,21 mm versus 34,19
+/- 4,03 mm for cases without and with CAD, resp.) and diastolic aortic diameters
measured 3 cm above aortic valve compared to patients without CAD (33,56 +/- 4,07
mm versus 29,75 +/- 3,12 mm). The systolic and diastolic diameters were
significantly higher in albuminuria positive patients compared to albuminuria
negative patients (p = 0.017 and 0.008, resp., for systolic and diastolic
diameters). CONCLUSION: In conclusion aortic diameters are increased in patients
with coronary artery disease and in patients with microalbuminuria. In CAD
patients, systolic blood pressure, pulse pressure, aortic systolic and diastolic
pressure, and albumin excretion rate were higher and aortic distensibility was
lower.
PMID- 26413552
TI - Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on
Renal Function and Histology in Rats.
AB - BACKGROUND: Ischemic postconditioning (IP) in renal Ischemia reperfusion injury
(IRI) models improves renal function after IRI. Ketamine affords significant
benefits against IRI-induced acute kidney injury (AKI). The present study
investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine
in ischemia-reperfusion-induced AKI. METHODS: Forty-one Wistar rats were
randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion;
IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent
right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney
arterial occlusion for 30 min followed by reperfusion for 24 h. Complete
reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2
min of reperfusion. Renal function was assessed by measuring serum neutrophil
gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen
(BUN). Tubular damage was evaluated by renal histology. RESULTS: Creatinine and
BUN were significantly increased. Severe tubular injury was only observed in the
groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No
significant differences were detected between IPG and KIPG. CONCLUSIONS: No
synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was
observed in this rat model.
PMID- 26413553
TI - Reexamination of Statistical Methods for Comparative Anatomy: Examples of Its
Application and Comparisons with Other Parametric and Nonparametric Statistics.
AB - Various statistical methods have been published for comparative anatomy. However,
few studies compared parametric and nonparametric statistical methods. Moreover,
some previous studies using statistical method for comparative anatomy (SMCA)
proposed the formula for comparison of groups of anatomical structures (multiple
structures) among different species. The present paper described the usage of
SMCA and compared the results by SMCA with those by parametric test (t-test) and
nonparametric analyses (cladistics) of anatomical data. In conclusion, the SMCA
can offer a more exact and precise way to compare single and multiple anatomical
structures across different species, which requires analyses of nominal features
in comparative anatomy.
PMID- 26413551
TI - Volumetric Growth of the Liver in the Human Fetus: An Anatomical, Hydrostatic,
and Statistical Study.
AB - Using anatomical, hydrostatic, and statistical methods, liver volumes were
assessed in 69 human fetuses of both sexes aged 18-30 weeks. No sex differences
were found. The median of liver volume achieved by hydrostatic measurements
increased from 6.57 cm(3) at 18-21 weeks through 14.36 cm(3) at 22-25 weeks to
20.77 cm(3) at 26-30 weeks, according to the following regression: y = -26.95 +
1.74 * age +/- Z * (-3.15 + 0.27 * age). The median of liver volume calculated
indirectly according to the formula liver volume = 0.55 * liver length * liver
transverse diameter * liver sagittal diameter increased from 12.41 cm(3) at 18-21
weeks through 28.21 cm(3) at 22-25 weeks to 49.69 cm(3) at 26-30 weeks. There was
a strong relationship (r = 0.91, p < 0.001) between the liver volumes achieved by
hydrostatic (x) and indirect (y) methods, expressed by y = -0.05 + 2.16x +/-
7.26. The liver volume should be calculated as follows liver volume = 0.26 *
liver length * liver transverse diameter * liver sagittal diameter. The age
specific liver volumes are of great relevance in the evaluation of the normal
hepatic growth and the early diagnosis of fetal micro- and macrosomias.
PMID- 26413554
TI - Preterm Birth: A Prominent Risk Factor for Low Apgar Scores.
AB - OBJECTIVE: To determine predictive risk factors for Apgar scores < 7 at 5 minutes
at two hospitals providing tertiary care and secondary care, respectively.
METHODS: A retrospective registry cohort study of 21126 births (2006-2010) using
data from digital medical records. Risk factors were analyzed by logistic
regression analyses. RESULTS: AS(5 min) < 7 was multivariately associated with
the following: preterm birth; gestational week 32 + 0-36 + 6, OR = 3.9 (95% CI
2.9-5.3); week 28 + 0-31 + 6, OR = 8 (5-12); week < 28 + 0, OR = 15 (8-29);
postterm birth, OR = 2.0 (1.7-2.3); multiple pregnancy, OR = 3.53 (1.79-6.96);
previous cesarean section, OR = 3.67 (2.31-5.81); BMI 25-29, OR = 1.30 (1.09
1.55); BMI >= 30 OR = 1.70 (1.20-2.41); nonnormal CTG at admission, OR = 1.98
(1.48-2.66). >= 1-para was associated with a decreased risk for AS(5 min) < 7, OR
= 0.34 (0.25-0.47). In the univariate logistic regression analysis AS(5 min) < 7
was associated with tertiary level care, OR = 1.48 (1.17-1.87); however, in the
multivariate analysis there was no significant difference. CONCLUSION: A number
of partially preventable risk factors were identified, preterm birth being the
most evident. Further, no significant difference between the two hospital levels
regarding the risk for low Apgar scores was detected.
PMID- 26413556
TI - Axons take a dive: Specialized contacts of serotonergic axons with cells in the
walls of the lateral ventricles in mice and humans.
AB - In the walls of the lateral ventricles of the adult mammalian brain, neural stem
cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular
subventricular zone (V-SVZ). In a recent article, we show that supraependymal
serotonergic (5HT) axons originating from the raphe nuclei in mice form an
extensive plexus on the walls of the lateral ventricles where they contact E1
cells and NSCs. Here we further characterize the contacts between 5HT
supraependymal axons and E1 cells in mice, and show that suprependymal axons
tightly associated to E1 cells are also present in the walls of the human lateral
ventricles. These observations raise interesting questions about the function of
supraependymal axons in the regulation of E1 cells.
PMID- 26413555
TI - Isolation and Purification of Satellite Cells for Skeletal Muscle Tissue
Engineering.
AB - Engineered skeletal muscle holds promise as a source of graft tissue for the
repair of traumatic injuries such as volumetric muscle loss. The resident
skeletal muscle stem cell, the satellite cell, has been identified as an ideal
progenitor for tissue engineering due to its role as an essential player in the
potent skeletal muscle regeneration mechanism. A significant challenge facing
tissue engineers, however, is the isolation of sufficiently large satellite cell
populations with high purity. The two common isolation techniques, single fiber
explant culture and enzymatic dissociation, can yield either a highly pure
satellite cell population or a suitably large number or cells but fail to do both
simultaneously. As a result, it is often necessary to use a purification
technique such as pre-plating or cell sorting to enrich the satellite cell
population post-isolation. Furthermore, the absence of complex chemical and
biophysical cues influencing the in vivo satellite cell "niche" complicates the
culture of isolated satellite cells. Techniques under investigation to maximize
myogenic proliferation and differentiation in vitro are described in this
article, along with current methods for isolating and purifying satellite cells.
PMID- 26413557
TI - Biomimetic Scaffolds for Osteogenesis.
AB - Skeletal regenerative medicine emerged as a field of investigation to address
large osseous deficiencies secondary to congenital, traumatic, and post-oncologic
conditions. Although autologous bone grafts have been the gold standard for
reconstruction of skeletal defects, donor site morbidity remains a significant
limitation. To address these limitations, contemporary bone tissue engineering
research aims to target delivery of osteogenic cells and growth factors in a
defined three dimensional space using scaffolding material. Using bone as a
template, biomimetic strategies in scaffold engineering unite organic and
inorganic components in an optimal configuration to both support osteoinduction
as well as osteoconduction. This article reviews the various structural and
functional considerations behind the development of effective biomimetic
scaffolds for osteogenesis and highlights strategies for enhancing osteogenesis.
PMID- 26413558
TI - Breastfeeding after Anesthesia: A Review for Anesthesia Providers Regarding the
Transfer of Medications into Breast Milk.
AB - Doctors, nurses, and midwives often inform mothers to "pump and dump" their
breast milk for 24 hours after receiving anesthesia to avoid passing medications
to the infant. This advice, though cautious, is probably outdated. This review
highlights the more recent literature regarding common anesthesia medications,
their passage into breast milk, and medication effects observed in breastfed
infants. We suggest continuing breastfeeding after anesthesia when the mother is
awake, alert, and able to hold her infant. We recommend multiple types of
medications for pain relief while minimizing sedating medications. Few
medications can have sedating effects to the infant, but those medications are
specifically outlined. For additional safety, anesthesia providers and patients
may screen medications using the National Institute of Health' LactMed database.
PMID- 26413559
TI - Utilizing Multidimensional Measures of Race in Education Research: The Case of
Teacher Perceptions.
AB - Education scholarship on race using quantitative data analysis consists largely
of studies on the black-white dichotomy, and more recently, on the experiences of
student within conventional racial/ethnic categories (white, Hispanic/Latina/o,
Asian, black). Despite substantial shifts in the racial and ethnic composition of
American children, studies continue to overlook the diverse racialized
experiences for students of Asian and Latina/o descent, the racialization of
immigration status, and the educational experiences of Native American students.
This study provides one possible strategy for developing multidimensional
measures of race using large-scale datasets and demonstrates the utility of
multidimensional measures for examining educational inequality, using teacher
perceptions of student behavior as a case in point. With data from the first
grade wave of the Early Childhood Longitudinal Study, Kindergarten Cohort of 1998
1999, I examine differences in teacher ratings of Externalizing Problem Behaviors
and Approaches to Learning across fourteen racialized subgroups at the
intersections of race, ethnicity, and immigrant status. Results show substantial
subgroup variation in teacher perceptions of problem and learning behaviors,
while also highlighting key points of divergence and convergence within
conventional racial/ethnic categories.
PMID- 26413560
TI - Optical sectioning using a digital Fresnel incoherent-holography-based confocal
imaging system.
AB - We propose a new type of confocal microscope using Fresnel incoherent correlation
holography (FINCH). Presented here is a confocal configuration of FINCH using a
phase pinhole and point illumination that is able to suppress out-of-focus
information from the recorded hologram and hence combine the super-resolution
capabilities of FINCH with the sectioning capabilities of confocal microscopy.
PMID- 26413562
TI - Oral glucose tolerance testing to modulate plasma amyloid levels: A novel
biomarker.
AB - INTRODUCTION: Plasma levels of amyloid-beta (Abeta) do not correlate well with
different stages of Alzheimer's disease (AD) in cross-sectional studies.
Measuring the changes in Abeta plasma levels with an acute intervention may be
more sensitive to distinguishing individuals in earlier stages of AD (mild
cognitive impairment; MCI) from normal controls. METHODS: 57 participants (18
with AD/MCI and 39 cognitively normal controls) underwent oral glucose tolerance
testing (OGTT). Blood samples were obtained over a 2 hour time period. Changes in
plasma Abeta40 and42 levels were measured from either baseline or 5 minutes to
the 10 minute time point. RESULTS: Compared to normal controls, subjects with
AD/MCI had significantly less change (Delta) in plasma levels for both Abeta40(
3.13(40.93)pg/ml vs. 41.34(57.16)pg/ml;p=0.002) and Abeta42(-0.15(3.77)pg/ml vs.
5.64(10.65)pg/ml; p=0.004). DISCUSSION: OGTT combined with measures of plasma
Abeta40 and 42 is potentially useful in distinguishing aging individuals who are
in different stages of AD.
PMID- 26413563
TI - An Experimental Realization of a Chaos-Based Secure Communication Using Arduino
Microcontrollers.
AB - Security and secrecy are some of the important concerns in the communications
world. In the last years, several encryption techniques have been proposed in
order to improve the secrecy of the information transmitted. Chaos-based
encryption techniques are being widely studied as part of the problem because of
the highly unpredictable and random-look nature of the chaotic signals. In this
paper we propose a digital-based communication system that uses the logistic map
which is a mathematically simple model that is chaotic under certain conditions.
The input message signal is modulated using a simple Delta modulator and
encrypted using a logistic map. The key signal is also encrypted using the same
logistic map with different initial conditions. In the receiver side, the binary
coded message is decrypted using the encrypted key signal that is sent through
one of the communication channels. The proposed scheme is experimentally tested
using Arduino shields which are simple yet powerful development kits that allows
for the implementation of the communication system for testing purposes.
PMID- 26413561
TI - Outcomes after viral load rebound on first-line antiretroviraltreatment in
children with HIV in the UK and Ireland: an observational cohort study.
AB - BACKGROUND: About a third of children with HIV have virological failure within 2
years of beginning antiretroviral treatment (ART). We assessed the probability of
switch to second-line ART or virological re-suppression without switch in
children who had virological rebound on first-line ART in the UK and Ireland.
METHODS: In this study, we used data reported to the Collaborative HIV Paediatric
Study (CHIPS), a national multicentre observational cohort. We included children
with virological rebound (confirmed viral load>400 copies per mL after
suppression<400 copies per mL) on first-line ART. We did a competing-risk
analysis to estimate the probability of switch to second-line treatment,
confirmed resuppression (two consecutive viral load measurments<400 copies per
mL) without switch, and continued viral load above 400 copies per mL without
switch. We also assessed factors that predicted a faster time to switch.
FINDINGS: Of the 900 children starting first-line ART who had a viral load below
400 copies per mL within a year of starting treatment, 170 (19%) had virological
rebound by a median of 20.6 months (IQR 9.7-40.5). At rebound, median age was
10.6 years (5.6-13.4), median viral load was 3.6 log10 copies per mL (3.1-4.2),
and median CD4% was 24% (17-32). 89 patients (52%) switched to second-line ART at
a median of 4.9 months (1.7-13.4) after virological rebound, 53 (31%)
resuppressed without switch (19 [61%] of 31 patients on a first-line regimen that
included a protease inhibitor and 31 [24%] of 127 patients on a first-line
regimen that included a non-nucleoside reverse transcriptase inhibitor; NNRTI),
and 28 (16%) neither resuppressed nor switched. At 12 months after rebound, the
estimated probability of switch was 38% (95% CI 30-45) and of resuppression was
27% (21-34). Faster time to switch was associated with a higher viral load
(p<0.0001), later calendar year at virological rebound (p=0.02), and being on an
NNRTI-based or triple nucleoside reverse transcriptase inhibitor-based versus
protease-inhibitor-based first-line regimen (p=0.001). INTERPRETATION: A third of
children with virological rebound resuppressed without switch. Clinicians should
consider the possibility of resuppression with adherence support before switching
treatment in children with HIV. FUNDING: NHS England (London Specialised
Commissioning Group).
PMID- 26413565
TI - Laminar Wall Jet Flow and Heat Transfer over a Shallow Cavity.
AB - This paper presents the detailed simulation of two-dimensional incompressible
laminar wall jet flow over a shallow cavity. The flow characteristics of wall jet
with respect to aspect ratio (AR), step length (X u), and Reynolds number (Re) of
the shallow cavity are expressed. For higher accuracy, third-order discretization
is applied for momentum equation which is solved using QUICK scheme with SIMPLE
algorithm for pressure-velocity coupling. Low Reynolds numbers 25, 50, 100, 200,
400, and 600 are assigned for simulation. Results are presented for streamline
contour, velocity contour, and vorticity formation at wall and also velocity
profiles are reported. The detailed study of vortex formation on shallow cavity
region is presented for various AR, X u , and Re conditions which led to key
findings as Re increases and vortex formation moves from leading edge to trailing
edge of the wall. Distance between vortices increases when the step length (X u)
increases. When Re increases, the maximum temperature contour distributions take
place in shallow cavity region and highest convection heat transfer is obtained
in heated walls. The finite volume code (FLUENT) is used for solving Navier
Stokes equations and GAMBIT for modeling and meshing.
PMID- 26413564
TI - Risk Factors for Depression in Children and Adolescents with High Functioning
Autism Spectrum Disorders.
AB - The objective of our study was to examine, discuss, and provide proposals on
diagnostic comorbidity of depression in children and adolescents with high
functioning autism spectrum disorder (HFASD) in the following aspects. (1)
Prevalence. It was concluded that there are an elevated depression rate and the
need for longitudinal studies to determine prevalence and incidence based on
functioning level, autistic symptoms, gender, age, type of depression, prognosis,
duration, and treatment. (2) Explicative Hypotheses and Vulnerability. The
factors that present the greatest specific risk are higher cognitive functioning,
self-awareness of deficit, capacity for introspection, stressful life events,
adolescence, quality of social relationships, and alexithymia. (3) Risk of
Suicide. The need for control and detection of suicidal tendencies and bullying
is emphasised. (4) Depressive Symptoms. Indicators for early detection are
proposed and their overlap with HFASD is analysed, examining the assessment
techniques used and arguing that specific adapted tests are needed.
PMID- 26413566
TI - Comparison of Subcuticular Suture Materials in Cesarean Skin Closure.
AB - Aim. Comparison of the rate of wound complications, pain, and patient
satisfaction based on used subcuticular suture material. Methods. A total of 250
consecutive women undergoing primary and repeat cesarean section with low
transverse incision were prospectively included. The primary outcome was wound
complication rate including infection, dehiscence, hematoma, and hypertrophic
scar formation within a 6-week period after operation. Secondary outcomes were
skin closure time, the need for use of additional analgesic agent, pain score on
numeric rating scale, cosmetic score, and patient scar satisfaction scale.
Results. Absorbable polyglactin was used in 108 patients and nonabsorbable
polypropylene was used in 142 patients. Wound complication rates were similar in
primary and repeat cesarean groups based on the type of suture material. Skin
closure time is longer in nonabsorbable suture material group in both primary and
repeat cesarean groups. There was no difference between groups in terms of
postoperative pain, need for additional analgesic use, late phase pain, and
itching at the scar. Although the cosmetic results tended to be better in the
nonabsorbable group in primary surgery patients, there was no significant
difference in the visual satisfaction of the patients. Conclusions. Absorbable
and nonabsorbable suture materials are comparable in cesarean section operation
skin closure.
PMID- 26413567
TI - An Assessment of the Clinical and Economic Impact of Establishing Ileocolic
Anastomoses in Right-Colon Resection Surgeries Using Mechanical Staplers Compared
to Hand-Sewn Technique.
AB - Purpose. To estimate and compare clinical outcomes and costs associated with
mechanical stapling versus hand-sewn sutured technique in creation of ileocolic
anastomoses after right sided colon surgery. Methods. A previously conducted meta
analysis was updated for estimates of anastomotic leak rates and other clinical
outcomes. A value analysis model was developed to estimate cost savings due to
improved outcomes in a hypothetical cohort of 100 patients who underwent right
colon surgery involving either mechanical stapling or hand-sewn anastomoses. Cost
data were obtained from publicly available literature. Results. Findings from the
updated meta-analysis reported that the mechanical stapling group had lower
anastomotic leaks 2.4% (n = 11/457) compared to the hand-sewn group 6.1% leaks
(n = 44/715). Utilizing this data, the value analysis model estimated total
potential cost savings for a hospital to be around $1,130,656 for the 100-patient
cohort using mechanical stapling instead of hand-sewn suturing, after accounting
for incremental supplies cost of $49,400. These savings were attributed to lower
index surgery costs, reduced OR time costs, and reduced reoperation costs driven
by lower anastomotic leak rates associated with mechanical stapling. Conclusion.
Mechanical stapling can be considered as a clinically and economically favorable
option compared to suturing for establishing anastomoses in patients undergoing
right colon surgery.
PMID- 26413569
TI - Conducting Research with Vulnerable Populations: Cautions and Considerations in
Interpreting Outliers in Disparities Research.
AB - Addressing the needs of understudied and vulnerable populations first and
foremost necessitate correct application and interpretation of research that is
designed to understand sources of disparities in healthcare or health systems
outcomes. In this brief research report, we discuss some important concerns and
considerations in handling "outliers" when conducting disparities-related
research. To illustrate these concerns, we use data from our recently completed
study that investigated sources of disparities in cancer pain outcomes between
African Americans and Whites with cancer-related pain. A choice-based conjoint
(CBC) study was conducted to compare preferences for analgesic treatment for
cancer pain between African Americans and Whites. Compared to Whites, African
Americans were both disproportionately more likely to make pain treatment
decisions based on analgesic side-effects and were more likely to have extreme
values for the CBC-elicited utilities for analgesic "side-effects." Our findings
raise conceptual and methodological consideration in handling extreme values when
conducting disparities-related research. Extreme values or outliers can be caused
by random variations, measurement errors, or true heterogeneity in a clinical
phenomenon. The researchers should consider: 1) whether systematic patterns of
extreme values exist and 2) if systematic patterns of extreme values are
consistent with a clinical pattern (e.g., poor management of cancer pain and side
effects in racial/ethnic subgroups as documented by many previous studies). As
may be evident, these considerations are particularly important in health
disparities research where extreme values may actually represent a clinical
reality, such as unequal treatment or disproportionate burden of symptoms in
certain subgroups. Approaches to handling outliers, such as non-parametric
analyses, log transforming clinically important extreme values, or removing
outliers may represent a missed opportunity in understanding a potentially
targetable area of intervention.
PMID- 26413568
TI - Porosome in Cystic Fibrosis.
AB - Macromolecular structures embedded in the cell plasma membrane called
'porosomes', are involved in the regulated fractional release of intravesicular
contents from cells during secretion. Porosomes range in size from 15 nm in
neurons and astrocytes to 100-180 nm in the exocrine pancreas and neuroendocrine
cells. Porosomes have been isolated from a number of cells, and their morphology,
composition, and functional reconstitution well documented. The 3D contour map of
the assembly of proteins within the porosome complex, and its native X-ray
solution structure at sub-nm resolution has also advanced. This understanding now
provides a platform to address diseases that may result from secretory defects.
Water and ion binding to mucin impart hydration, critical for regulating
viscosity of the mucus in the airways epithelia. Appropriate viscosity is
required for the movement of mucus by the underlying cilia. Hence secretion of
more viscous mucus prevents its proper transport, resulting in chronic and fatal
airways disease such as cystic fibrosis (CF). CF is caused by the malfunction of
CF transmembrane conductance regulator (CFTR), a chloride channel transporter,
resulting in viscous mucus in the airways. Studies in mice lacking functional
CFTR secrete highly viscous mucous that adhered to the epithelium. Since CFTR is
known to interact with the t-SNARE protein syntaxin-1A, and with the chloride
channel CLC-3, which are also components of the porosome complex, the
interactions between CFTR and the porosome complex in the mucin-secreting human
airway epithelial cell line Calu-3 was hypothesized and tested. Results from the
study demonstrate the presence of approximately 100 nm in size porosome complex
composed of 34 proteins at the cell plasma membrane in Calu-3 cells, and the
association of CFTR with the complex. In comparison, the nuclear pore complex
measures 120 nm and is comprised of over 500 protein molecules. The involvement
of CFTR in porosome-mediated mucin secretion is hypothesized, and is currently
being tested.
PMID- 26413570
TI - Stem Cell Therapy for Sensorineural Hearing Loss, Still Alive?
AB - In mammals, the auditory system, which includes the cochlea, has a very complex
structure harboring many types of cells performing different functions. Among
these cells are the auditory hair cells (HCs), which are terminally and well
differentiated unique cells which have lost their regenerative potential after
development. The auditory HCs are easily damaged by aging as well as during
episodes of ototoxicity and acoustic trauma. HCs damages typically occur in the
early stage of injury and can result a permanent hearing loss. Recently, there
have been tremendous developments from stem cells (SCs) research involving
sensorineural hearing loss, but several limitations and obstacles persist in
allowing these developments from continuing onto clinical applications. This
review discusses the recent advances in SC research in sensorineural hearing loss
with the subsequent sections discussing the possible hurdles and limitations that
currently preclude their clinical application.
PMID- 26413571
TI - Test-Retest Reliability of Word Recognition Score Using Korean Standard
Monosyllabic Word Lists for Adults as a Function of the Number of Test Words.
AB - BACKGROUND AND OBJECTIVES: The purpose was to establish the test-retest
reliability of word recognition score (WRS) using Korean standard monosyllabic
word lists for adults (KS-MWL-A) recently developed based on the international
standard for speech audiometry (ISO 8253-3:2012). SUBJECTS AND METHODS: Subjects
consisted of 159 adults aged to 18 to 25 years with normal hearing sensitivity.
WRSs were obtained in 2 dB steps from the level of speech recognition thresholds
to the level of 86% correct responses or greater. After one or two weeks, retest
was performed. Correlation, confidence interval (CI) and prediction interval (PI)
were calculated for the reliability. RESULTS: Correlation coefficients were 0.88
for 50 test words, 0.76 for 25 and 0.61 for 10 words. Results also showed that
95% CIs and PIs were narrower for 25 and 50 test words than those for 10 test
words. CONCLUSIONS: Korean WRS using the KS-MWL-A has high reliability for 25 and
50 test words, but relatively low for 10 words. It suggested that 95% CIs for
each test words would be criteria for significant differences in WRS for groups
and 95% PIs at each score of WRS could be utilized for a considerable difference
for each individual at retest.
PMID- 26413572
TI - Long-Term Outcomes of Acute Low-Tone Hearing Loss.
AB - BACKGROUND AND OBJECTIVES: Although acute low-tone hearing loss has been
associated with cochlear hydrops or early stage Meniere's disease, its prognosis
in the short-term has been reported to be better than sudden hearing loss.
However, recurrence of hearing loss and possible progression to Meniere's disease
remain important concerns in the clinical setting. This study aims to investigate
the long-term audiological outcomes of acute low-tone hearing loss. SUBJECTS AND
METHODS: A retrospective review of patients presenting with a first attack of
acute low-tone hearing loss was performed. Of the 77 patients, 33 were followed
up for more than 3 months. Progression, recovery of hearing loss and recurrence
of hearing loss were examined. Also, correlation between long-term outcomes and
associated clinical factors were analyzed. RESULTS: Twenty-five patients (75.7%)
had complete hearing recovery, five patients (15.1%) had partial recovery, two
patients (6.0%) had no recovery, and one patient (3.0%) had progression of
hearing loss 1 month after initial treatment. Thirty-three patients were followed
up for more than 3 months (mean 22 months, range 3-79 months). Recurrences of
acute low-tone hearing loss were observed in five patients (15.2%). All of the
recurrences occurred during the first 12 months of follow-up. Long-term prognosis
correlated with the initial therapy results (R(2)=0.693). CONCLUSIONS:
Recurrences of hearing loss were documented in five patients (15.2%), and all of
these cases occurred within one year of the first attack. Audiological outcomes
after initial therapy may predict the recurrence of acute low-tone hearing loss.
PMID- 26413573
TI - Measurement of Acceptable Noise Level with Background Music.
AB - BACKGROUND AND OBJECTIVES: Acceptable noise level (ANL) is a measure of the
maximum background noise level (BNL) that a person is willing to tolerate while
following a target story. Although researchers have used various sources of
target sound in ANL measures, a limited type of background noise has been used.
Extending the previous study of Gordon-Hickey & Moore (2007), the current study
determined the effect of music genre and tempo on ANLs as possible factors
affecting ANLs. We also investigated the relationships between individual ANLs
and the familiarity of music samples and between music ANLs and subjective
preference. SUBJECTS AND METHODS: Forty-one participants were seperated into two
groups according to their ANLs, 29 low-ANL listeners and 12 high-ANL listeners.
Using Korean ANL material, the individual ANLs were measured based on the
listeners' most comfortable listening level and BNL. The ANLs were measured in
six conditions, with different music tempo (fast, slow) and genre (K-pop, pop,
classical) in a counterbalanced order. RESULTS: Overall, ANLs did not differ by
the tempo of background music, but music genre significantly affected individual
ANLs. We observed relatively higher ANLs with K-pop music and relatively lower
ANLs with classical music. This tendency was similar in both low-ANL and high-ANL
groups. However, the subjective ratings of music familiarity and preference
affected ANLs differently for low-ANL and high-ANL groups. In contrast to the low
ANL listeners, the ANLs of the high-ANL listeners were significantly affected by
music familiarity and preference. CONCLUSIONS: The genre of background music
affected ANLs obtained using background music. The degree of music familiarity
and preference appears to be associated with individual susceptibility to
background music only for listeners who are greatly annoyed by background noise
(high-ANL listeners).
PMID- 26413575
TI - Hearing Thresholds for a Geriatric Population Composed of Korean Males and
Females.
AB - BACKGROUND AND OBJECTIVES: The purpose of the present study was to provide the
hearing threshold levels in the elderly Korean population, and to compare Korean
data with that in the International Organization for Standardization (ISO) 7029
(2000). SUBJECTS AND METHODS: Data were collected from a total of 526 ears from
112 males and 151 females aged 60-84 years. All participants were screened
otologically by the procedure given in ISO 8253-1 (2010). RESULTS: Results showed
that the pure-tone average was gradually elevated with increasing age. The amount
of hearing loss was greater in males than in females, and the high frequency
hearing thresholds were worse than the low frequency hearing thresholds in males
and females. The hearing threshold levels were higher at low frequencies in males
and at all frequencies in females than the norms of ISO 7029 (2000). CONCLUSIONS:
Results from this study will be partly used for standardization of hearing
thresholds as a function of age in Korea and for updating the ISO 7029.
PMID- 26413574
TI - The Effect of Korean Red Ginseng on Symptoms and Quality of Life in Chronic
Tinnitus: A Randomized, Open-Label Pilot Study.
AB - BACKGROUND AND OBJECTIVES: The major mechanism of inner ear cell damage is the
production of reactive oxygen species (ROS). Korean red ginseng (KRG) has an anti
ROS effect; thus we hypothesized that KRG may be of use for the treatment of
chronic idiopathic tinnitus. The aim of the study is to investigate clinical
outcomes and health-related quality of life (QoL) in chronic tinnitus patients
after taking KRG. SUBJECTS AND METHODS: This study was an open-label randomized
controlled trial. Sixty-one patients with chronic tinnitus were enrolled and
randomized to three groups. The control group was treated for 4 weeks with 160
mg/day Ginkgo biloba extract, and two other groups receiving 1500 mg/day or 3000
mg/day KRG for 4 weeks. Clinical assessments were performed using the tinnitus
handicap inventory (THI), Visual Analogue Scale (VAS) and QoL was assessed by
Short Form-36 Health Survey (SF-36) questionnaire. RESULTS: Fifty-nine patients
completed the planned protocol. Significant improvements were observed between
initial and post-treatment THI scores in patients receiving 3000 mg/day KRG.
There was no statistically significant difference between initial and post
treatment VAS scores in all groups. Treatment with 3000 mg/day KRG for 4 weeks
significantly improved role emotional and mental health scores in the SF-36
survey. CONCLUSIONS: These results suggest that KRG may improve tinnitus symptoms
and mental wellbeing in chronic tinnitus patients.
PMID- 26413576
TI - The Dynamic Range for Korean Standard Sentence Material: A Gender Comparison in a
Male and a Female Speakers.
AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to identify differences
between the dynamic ranges (DRs) of male and female speakers using Korean
standard sentence material. Consideration was especially given to effects within
the predefined segmentalized frequency-bands. MATERIALS AND METHODS: We used
Korean standard sentence lists for adults as stimuli. Each sentence was
normalized to a root-mean-square of 65 dB sound pressure level. The sentences
were then modified to ensure there were no pauses, and the modified sentences
were passed through a filter bank in order to perform the frequency analysis.
Finally, the DR was quantified using a histogram that showed the cumulative
envelope distribution levels of the speech in each frequency band. RESULTS: In
DRs that were averaged across all frequency bands, there were no significant
differences between the male and the female speakers. However, when considering
effects within the predefined frequency bands, there were significant differences
in several frequency bands between the DRs of male speech and those of female
speech. CONCLUSIONS: This study shows that the DR of speech for the male speaker
differed from the female speaker in nine frequency bands among 21 frequency
bands. These observed differences suggest that a standardized DR of male speech
in the band-audibility function of the speech intelligibility index may differ
from that of female speech derived in the same way. Further studies are required
to derive standardized DRs for Korean speakers.
PMID- 26413577
TI - Objective Tinnitus Concomitant with Eye Blinking: A Case Report.
AB - Tinnitus is a common auditory phenomenon associated with many otological
diseases, and is usually subjective. Objective tinnitus can be generated by para
auditory structures, usually derived from vascular or myogenic sources, or the
eustachian tube. We present a rare case of intermittent unilateral tinnitus
associated with eye blinking. Otoendoscopic examination showed that the external
auditory canals and tympanic membranes were normal; however, rhythmic movements
of both tympanic membranes, concomitant with the tinnitus, were evident whenever
the patient blinked. The tympanometry and stapedial reflexes measured via
impedance audiometry exhibited saw-tooth patterns; movement of the tympanic
membrane was associated with eyelid blinking. The patient was managed
conservatively, with reassurance and medication, and the condition became well
controlled. Here, we present this educational case and review the literature.
PMID- 26413578
TI - Persistent Positional Vertigo in a Patient with Sudden Sensorineural Hearing
Loss: A Case Report.
AB - Because inner ear organs are interconnected through the endolymph and surrounding
endolymphatic membrane, the patients with sudden sensorineural hearing loss
(SSNHL) often complain of vertigo. In this study, we report a patient with SSNHL
accompanied by persistent positional vertigo, and serial findings of head-roll
tests are described. At acute stage, head-roll test showed persistent geotropic
direction-changing positional nystagmus (DCPN), which led to a diagnosis of SSNHL
and ipsilateral light cupula. Although vertigo symptom gradually improved,
positional vertigo lasted for more than 3 weeks. At this chronic stage,
persistent apogeotropic DCPN was observed in a head roll test, which led to a
diagnosis of the heavy cupula. Although the mechanism for the conversion of
nystagmus direction from geotropic to apogeotropic persistent DCPN is unclear,
the change of specific gravity of the endolymph might be one of the plausible
hypothetical explanations.
PMID- 26413579
TI - Skin Flap Necrosis by Bone Marking with Methylene Blue in Cochlear Implantation.
AB - One of surgical complications in cochlear implantation is the necrosis of the
skin flap above the receiver-stimulator coil. We present a case of 55-year-old
woman who underwent cochlear implantation and developed a bluish skin necrosis
due to bone marking. The planned position for the receiver-stimulator was marked
using methylene blue through skin to bone. She did not undergo skin flap thinning
and underwent successful implantation with complete electrode insertion. Few
weeks postoperatively, the patient developed bluish discoloration with
progressive thick, blue eschar formation and skin flap necrosis. She subsequently
underwent wound debridement and skin flap closure. Cochlear explantation was not
necessary. Timely diagnosis and management about this complication is necessary
to prevent further skin breakdown and subsequent device extrusion. This report
identifies the marking using methylene blue as another possible source of skin
flap necrosis in cochlear implantation, and surgeons should be aware of this
potential complication.
PMID- 26413580
TI - Understanding the Role of Medical Experts during a Public Health Crisis Digital
Tools and Library Resources for Research on the 1918 Spanish Influenza.
AB - Humanities scholars, particularly historians of health and disease, can benefit
from digitized library collections and tools such as topic modeling. Using a case
study from the 1918 Spanish Flu epidemic, this paper explores the application of
a big humanities approach to understanding the impact of a public health official
on the course of the disease and the response of the public, as documented
through digitized newspapers and medical periodicals.
PMID- 26413581
TI - Optimal kVp Selection for Contrast CT Imaging Based on a Projection-domain
Method.
AB - Computed Tomography (CT) has been in clinical use for several decades. The number
of CT scans has increased significantly worldwide, which results in increased
radiation dose delivered to the general population. Many technologies have been
developed to minimize the dose from CT scans, including scanner hardware
improvements, task-specific protocol design and advanced reconstruction
algorithms. In this study, we focused on selection of X-ray tube voltage and
filtration to achieve optimal dose efficiency given required image quality, more
specifically the contrast to noise ratio. Our approach differs from previous
studies in two aspects. Typically, Monte-Carlo simulation is used to estimate
dose in simulations, but this is computationally costly. We instead use a
projection-domain dose estimation method. No image reconstruction is required for
the projection-domain method, which further simplifies the analysis. This study
also includes tantalum, a new contrast agent, in addition to soft tissue (water),
bone and iodine contrast. Optimal tube voltages and filtration are identified as
a function of phantom size. The simulation analysis is confirmed with a limited
phantom study.
PMID- 26413582
TI - Weaving Clinical Expertise in Online Health Communities.
AB - Many patients visit online health communities to receive support. In face-to-face
support groups, health professionals facilitate peer-patients exchanging
experience while adding their clinical expertise when necessary. However, the
large scale of online health communities makes it challenging for such health
professional moderators' involvement to happen. To address this challenge of
delivering clinical expertise to where patients need them, we explore the idea of
semi-automatically providing clinical expertise in online health communities. We
interviewed 14 clinicians showing them example peer-patient conversation threads.
From the interviews, we examined the ideal practice of clinicians providing
expertise to patients. The clinicians continuously assessed when peer-patients
were providing appropriate support, what kinds of clinical help they could give
online, and when to defer to patients' healthcare providers. The findings inform
requirements for building a semi-automated system delivering clinical expertise
in online health communities.
PMID- 26413583
TI - The Language Abilities of Resident Physicians.
AB - PURPOSE: The Joint Commission mandates that health care systems provide
culturally and linguistically appropriate care for patients. Similarly, the
Accreditation Council for Graduate Medical Education (ACGME) requires that
resident physicians learn to communicate effectively across cultures. The purpose
of this study was to analyze residents' self-report of fluency in a second
language and level of training in the use of interpreters to assess the
institution's preparation of residents to meet mandates regarding the delivery of
cross-cultural care. METHODS: Seven hundred and twenty two (722) surveys were
analyzed from resident physicians in 62 different ACGME accredited programs.
Language ability was measured with a survey question asking about comfort
providing patient care in a language other than English. Knowledge of working
with interpreters was measured by a survey question asking about amount of
training received. Survey questions on gender, post-graduate year (PGY),
specialty, and underrepresented minority (URM) status were examined using c2 and
independent samples Mann-Whitney U test. Logistic regression was used to estimate
the adjusted odds ratio by variable. RESULTS: Fifty-five percent of all of the
resident physicians endorsed feeling comfortable providing patient care in a
language other than English, and Spanish was the most common language (77%).
Almost 20% percent of residents reported little or no training in the use of
interpreters. In bivariate analysis, race-ethnicity was associated (P-value
<.001) with comfort in providing patient care in a language other than English.
Primary care resident physicians had a 1.67 adjusted odds ratio (95% confidence
interval [CI] 1.18, 2.37; p value = 0.004) of feeling comfortable providing
patient care in a language other than English compared to resident physicians
from other specialties. CONCLUSIONS: Primary care resident physicians are more
likely to report feeling comfortable in providing patient care in a language
other than English. Most residents would benefit from additional education in
working with interpreters.
PMID- 26413584
TI - Epilepsy genetics in Africa: challenges and future perspectives.
AB - Despite the diversity of the African population, genetic studies, of epilepsy in
particular, have been limited, especially in sub-Saharan Africa. In recent years,
with the regression of infectious diseases in developing countries, the focus has
shifted more towards non communicable disorders. The prevalence of epilepsy in
Africa is higher compared to other continents. Although this has been attributed
to the high rate of infectious diseases, genetic contributions should not be
ignored. Research in genetic epilepsy in Africa could well benefit from the
decreasing cost of genetic analysis, and could contribute to further our
knowledge on the spectrum of these diseases in Africa. The growing collaboration
between African research institutions and those of developed countries offers a
unique opportunity to boost research in Africa and improve our global
understanding of human disease, thus leading to the development of better
therapeutic approaches.
PMID- 26413586
TI - The construction of a two-dimensional supramolecular organic framework with
parallelogram pores and stepwise fluorescence enhancement.
AB - A novel single-layer two-dimensional (2D) supramolecular organic framework (SOF)
with parallelogram pores has been assembled to turn on the fluorescence emission
of a non-emissive building block, and the emission could be further enhanced by
the aggregation of the as-prepared 2D monolayers.
PMID- 26413587
TI - On-tip photodetection: a simple and universal platform for optoelectronic
screening.
AB - A novel platform for transient photodetector component screening has been
developed whereby an optical fiber tip serves as the counter electrode when
placed in a variety of dielectric media, connected to a photoresponsive working
electrode. The soft processing conditions allow for ubiquitous photodetection for
organic and biological systems.
PMID- 26413585
TI - Electronic communication of cells with a surface mediated by boronic acid
saccharide interactions.
AB - The fabrication of a molecularly tailored surface functionalised with a
saccharide binding motif, a phenyl boronic acid derivative is reported. The
functionalised surface facilitated the transfer of electrons, via unique
electronic interactions mediated by the presence of the boronic acid, from a
macrophage cell line. This is the first example of eukaryotic cellular-electrical
communication mediated by the binding of cells via their cell-surface saccharide
units.
PMID- 26413588
TI - Chemoselective reduction of the phosphoryl bond of O-alkyl phosphinates and
related compounds: an apparently impossible transformation.
AB - A method is reported for the phosphoryl bond cleavage of O-alkyl phosphinates,
phosphinothioates and certain phosphonamidates to furnish the corresponding
P(III) borane adducts. The two-step procedure relies upon initial activation of
the phosphoryl bond with an alkyl triflate, followed by reduction of the
resulting intermediate using lithium borohydride.
PMID- 26413589
TI - Tribute: John H. Laragh, MD.
PMID- 26413590
TI - Animal moves reveal bigger picture.
AB - As the performance of electronic tracking devices improves dramatically, their
use opens up new areas of investigation. The movements of individuals can be
linked to physiology, environmental conditions and group behaviour, report back
on otherwise inaccessible parts of the biosphere, and warn us of disease spread
and natural disasters. Michael Gross reports.
PMID- 26413592
TI - Environmental hazards, air pollution, and noise as novel cardiovascular risk
factors.
PMID- 26413591
TI - Melissa Bateson.
PMID- 26413593
TI - Reduce air pollution to reduce the burden of cardiovascular diseases!
AB - The second highest environmental risk factor for years of lives lost annually.
PMID- 26413594
TI - Stress and cardiovascular mortality: an evident but underestimated connection.
PMID- 26413595
TI - Stress and the heart: the role of type D personality in personalized care.
PMID- 26413596
TI - Music and the heart.
AB - Emeritus Professor of Cardiology Peter Sleight discusses his observations on how
music can affect heart rate variability and life expectancy.
PMID- 26413597
TI - The Asklepios project in perspective: the population on its way to ageing.
AB - Thierry Gillebert discusses an ambitious project that started in 2002 and is
ongoing.
PMID- 26413598
TI - European Heart for Children: a story of humanity and success.
AB - Since its foundation in 2009 and the last publications, European Heart for
Children has grown substantially.
PMID- 26413599
TI - [Editorial].
PMID- 26413600
TI - Reply to A Macri.
PMID- 26413601
TI - Removal of restrictions following primary THA with posterolateral approach does
not increase the risk of early dislocation--reply.
PMID- 26413602
TI - Cell-Penetrating Peptides. Preface.
PMID- 26413603
TI - Google Trends (GT) related to influenza--the authors reply.
PMID- 26413604
TI - Functionalized Gold Nanoparticles: Synthesis, Properties and Applications--A
Review.
AB - The past few decades have witnessed significant advances in the development of
functionalized gold nanoparticles for applications in various fields such as
chemistry, biology, pharmacy and physics. Although it has been more than 150
years since they were first synthesized, extensive research has recently been
undertaken to improve or modify gold nanoparticles, thereby opening up
opportunities to enhance and optimize their potential and breadth of their
applicability. Recently developed methods have allowed a precise control of gold
nanoparticle size and the modification of gold nanoparticles with suitable
protecting and functionalizing agents, facilitate their applications in different
areas such as chemical and biological sensing, imaging and biomedical
applications. This review focuses on the recent developments in various methods
for the size and shape controlled synthesis of gold nanoparticles, understanding
of different properties of gold nanoparticles and their applications in various
fields. Particular attention is given to the chemical and biological sensing
applications of gold nanoparticles and on the advances in the controlled ordering
of gold nanoparticles for creating nanostructures for diverse applications.
PMID- 26413605
TI - Recent Advances in Nonpolar and Semipolar InGaN Light-Emitting Diodes (LEDs).
AB - The III-nitrides have attracted much attention because of their applicability in
optoelectronic devices, whose emission wavelengths range from green to
ultraviolet light due to their wide band gap. However, conventional c-plane GaN
based devices are influenced significantly by spontaneous and piezoelectric
polarization effects, which could pose a limitation for increased luminous
efficiency as a result of the quantum confined stark effect. Since the early
2000s, many groups have tried to solve these problems by examining the growth of
GaN on non- or semipolar surface planes. High power non- and semipolar LEDs can
be realized by the growth of a thick active layer. In addition, it is expected
that it is possible to grow nonpolar InGaN LEDs with high quality p-GaN layers
due to lower hole activation energy, and also long-wavelength semipolar InGaN
LEDs because of the capacity for high indium incorporation in the quantum wells
(QWs). However, non- and semipolar structures grown on sapphire substrate usually
contain a high density of basal stacking faults and threading dislocations. For
this reason, the growth of non- and semipolar GaN-based LEDs on a sapphire
substrate has been attempted through the introduction of defect reduction
techniques such as epitaxial lateral overgrowth, patterned sapphire substrate and
re-growth techniques on a porous GaN layer, etc. Also, some researchers have
grown high quality non- and semipolar GaN-based LEDs using non- and semipolar
freestanding GaN substrates. In this review paper, we introduce and discuss
recent progress in the development of non- and semipolar GaN-based LEDs and
freestanding GaN substrates.
PMID- 26413606
TI - Vibration Damping Materials and Their Applications in Nano/Micro-Electro
Mechanical Systems: A Review.
AB - The present review explores an overall view of the vibration damping materials
ranging from traditionally used viscoelastic materials for macroscale damping to
hybrid thin film heterostructures for micro-electro-mechanical systems (MEMS).
Vibration damping materials like rubbers, polymers, metals, metal-matrix
composites and smart materials are reviewed in terms of damping capacity,
stiffness, mechanical strength and figure of merit. Nanoscale shape memory
alloys, piezoelectric materials, carbon nanotubes, their composites and thin
films are promising materials for future nanoscale damping devices. The main
focus of this article is on our development of new vibration damping approach for
MEMS structures comprising of ferroelastic/ferroelastic thin film
heterostructures. For the first time, nanoindentation has been explored as an
alternative tool to evaluate the damping capability of actual components (e.g.,
thin films for MEMS) where production of dynamic mechanical analyzer (DMA) test
samples is not feasible. A comprehensive insight on the existing vibration
damping materials and our new approach would definitely trigger some important
applications in nano- and micro-electro-mechanical systems.
PMID- 26413607
TI - Cancer Targeting: Responsive Polymers for Stimuli-Sensitive Drug Delivery.
AB - Effective treatment of cancer is limited by the lack of delivery technology to
specifically and efficiently deliver chemotherapeutic agents within the tumor
vicinity. The tumor targeting based on ligand or antibody conjugation to
therapeutics is limited by the chemistry, stability and scalability issues.
Recently, functional polymers which are responsive to internal and external
stimuli have been developed. Stimuli-responsive carriers show potential to
overcome the limitations of cancer targeting. Internal stimuli localized to
cancer tissue including pH, redox potential, extracellular enzyme expression can
be utilized to target tumors. Furthermore, polymer responsiveness to external
stimuli, including temperature, magnetic field, ultrasound and light can be
utilized to localize the nanocarriers to specific tumor location after
administration. The present review provides an overview of the current status of
development of responsive polymers for various stimuli to target cancer.
PMID- 26413608
TI - CRISPR/Cas: A Faster and More Efficient Gene Editing System.
AB - Gene editing technology has been at its mature stage with the successful
development of TALENs and CRISPR/Cas enzymes. The genetically modified
endonucleases of ZFNs, TALENs, and CRISPR/Cas are widely used in the development
of genetically modified cells or organisms. Among the enzymes that possess gene
editing ability, CRISPR/Cas is the latest member with high efficiency in gene
editing and simplicity in cloning. This review discusses the discovery of CRISPR,
the development of the CRISPR/Cas system, and its applications as a new gene
editing system.
PMID- 26413609
TI - Multifunctional Drug Delivery Systems Using Inorganic Nanomaterials: A Review.
AB - Targeted drug delivery with controlled rate is vital for therapeutic purpose
especially for cancer therapy. Advanced biomaterials with the aid of
nanotechnology have evolved as efficient drug delivery systems (DDS), providing a
multi-functional platform for simultaneous therapeutic and diagnostic
(theranostic) functions. This review discusses current advances in synthesis and
applications of inorganic materials such as quantum dots, carbon nanotubes and
graphene oxides for drug delivery. The strategies of surface-functionalization of
these inorganic materials to render them biocompatible are also reviewed. The
advantages and applications of these biomaterials as multi-functional moiety for
bio-imaging, drug targeting and delivery have been discussed. The review
concludes with discussion on challenges that limits the practical applications of
some materials as a drug carrier for therapeutic use. These issues remain to be
fully addressed for their maximum utilization for biomedical applications.
PMID- 26413610
TI - Analysis of Carrier Transport of Organic Devices by Using Nonlinear Optical
Polarization.
AB - In this review, we discuss the Maxwell-Wagner (MW) effect model analysis of
organic devices and time-resolved optical second harmonic generation (TR-EFISHG)
measurement that is available for directly probing carrier motion in organic
semiconductor devices. Using these, we show that organic field effect transistor
as well organic double-layer device operation is analyzed well, and we can make
clear the mechanism of these organic devices' operation. Finally, we conclude
that the dielectric physics approach using the MW model analysis and the TR
EFISHG experiment is useful to study carrier transport mechanism of organic
devices.
PMID- 26413611
TI - Recent Advances in Preparation, Structure, Properties and Applications of
Graphite Oxide.
AB - Graphite oxide, also referred as graphitic oxide or graphitic acid, is an
oxidized bulk product of graphite with a variable composition. However, it did
not receive immense attention until it was identified as an important and easily
obtainable precursor for the preparation of graphene. This inspired many
researchers to explore facts related to graphite oxide in exploiting its
fascinating features. The present article culminates up-dated review on different
preparative methods, morphology and characterization of physical/chemical
properties of graphite oxide by XRD, XPS, FTIR, Raman, NMR, UV-visible, and DRIFT
analyses. Finally, recent developments on intercalation and applications of GO in
multifaceted areas of catalysis, sensor, supercapacitors, water purification,
hydrogen storage and magnetic shielding etc. has also been reviewed.
PMID- 26413612
TI - Flexible and Conductive Graphene-Poly (diallyldimethylammoniumchloride)
Buckypaper.
AB - This paper describes the fabrication and characterization of flexible, conductive
reduced graphene oxide (rGO)-poly(diallyldimethylammoniumchloride) (PDDA)
buckypaper (BP). PDDA acts as a reducing agent to prepare an rGO-PDDA nanosheet
dispersion from graphite oxide. The incorporation of PDDA as a "glue" molecule
successfully binds rGO nanosheets into BPs with strong interlayer binding. The
resulting BPs were characterized by scanning electronic microscopy (SEM), Raman,
energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and
resistivity measurements. The sp2 structure was greatly restored by the PDDA
induced reduction. Moreover, rGO was chemically doped from the adsorbed PDDA,
which causes the Raman G band to shift from ~1585 to ~1610 cm(-1). This chemical
doping substantially increased the density of the free charge carriers in rGO and
thereby further enhanced the electrical conductivity of the rGO-BP. Good inter
layer connection in the rGO percolating network was obtained after thermal
annealing at higher than ~250 degrees C. The resulting rGO-PDDA-BPs exhibited an
isotropic sheet resistance as low as ~100 Omega/sq, which indicates a reduction
by six orders of magnitude compared to the GO-BPs resistance before annealing.
This PDDA-induced reduction with a low-temperature annealing process preserved
the BPs' structural integrity and mechanical flexibility, thus overcoming the
fragility problems with high-temperature annealing.
PMID- 26413613
TI - Preparation and Characterization of Photosensitive and Magnetic Targeting
Graphene Oxide Nanocomposite.
AB - Hematoporphyrin-conjugated magnetic graphene oxide nanocomposite was designed and
prepared as a novel promising model. Fe3O4 nanoparticles were dispersed on the
surface and edges of the graphene oxide in a uniform size, and hematoporphyrin
was effectively conjugated onto graphene oxide via hydrophobic interactions and
pi-pi stacking. With the photosensitivity of hematoporphyrin and the magnetic
properties of Fe3O4 nanoparticles, it can be applied for photodynamic therapy to
increase the accumulation of hematoporphyrin in tumor cells. The cytotoxicity in
vitro showed that hematoporphyrin conjugated magnetic graphene oxide
nanocomposite irradiated at 671 nm generated cytotoxic singlet oxygen and
exhibited a good inhibition to the human tumor cell HeLa (IC50 = 10.12 ug/ml),
which suggested that the nanocomposite is potential for targeting photodynamic
therapy as a promising drug delivery system.
PMID- 26413614
TI - Ultrasonication-Assisted Controllable Self-Assembly of Graphene Oxide.
AB - A facile, and cost-efficient ultrasonication-assisted exfoliation strategy is
proposed to fabricate GO sheets with various sizes. Just by controlling the
original GO sizes as basic building blocks in deionized water, various aligned
architectures, such as films, microfibers, submicron rods, and nanorods, are self
assembled at the water/air interface. The formation mechanisms are analyzed on
the basis of the morphology evolutions of various aligned architectures. It is
very interesting to note that various functional structures are generally aligned
in a certain direction, which is probably attributed to the intrinsic lamellar
orientation and the corresponding polarity of the GO sheets. This work provides a
beneficial reference for controlling the assembling behaviors of GO in a broad
range of applications.
PMID- 26413615
TI - Facile and Effective Functionalization of Graphene Oxide by Boron-Oxygen Covalent
or Bingel Cyclopropanation Reaction.
AB - Functionalized graphene oxide (GO-BPh2), was obtained via one step reaction
between triphenyl boron and oxygen-containing groups on graphene sheets. In
addition, functionalized graphene oxide (GO-Carbene) was obtained via bingel
cyclopropanation reaction of active double bands on graphene sheets. Both
functionalized materials can be homogeneously distributed into ortho
dichlorobenene. They were characterized by FTIR spectroscopy, UV Vis NIR
spectroscopy, thermal gravimetric analysis, raman spectra, and X-ray
photoelectron spectroscopy (XPS). FTIR, TGA and XPS results prove that phenyl
boron has been successfully attached to the graphene sheets by covalent bonds.
And the Raman spectra and XPS confirm that many carbon double bands changed into
carbon single bands on graphene sheets after cyclopropanation reaction.
PMID- 26413616
TI - Direct Ablation by Laser of Single Graphene Monolayer and Graphene/Photopolymer
Double Layer.
AB - A diode-pumped Q-switched neodymium-doped yttrium vanadate (Nd:YVO4, lambda =
1064 nm) laser was applied to obtain graphene patterns on a photopolymer layer by
direct ablation. In the transfer process of the graphene layer, the photopolymer
was employed as a graphene supporting layer and it was not removed for the
simplification of the process. The laser ablation was carried out on
graphene/photopolymer double layers for various beam conditions. The results
showed that the laser-ablated widths on the graphene/photopolymer double layer
were much greater than those on the graphene monolayer, especially at lower
scanning speeds and at higher repetition rates. The photopolymer layer was not
removed by the laser ablation, and the thermal energy was considered to have been
dissipated in the lateral direction of graphene instead of being conducted
vertically to the glass substrate. The Raman spectrum results showed that the
graphene layer was clearly removed on the laser-ablated region of interest.
PMID- 26413617
TI - Controllable and Reversible Dispersiblity of Graphene Materials by a Generic
Organometallic Functionalization.
AB - A general and reversible functionalization method has been developed for reduced
graphene oxide (rGO) based on a simple reaction sequence. In this sequence, the
chemical functionalization of reduced graphene oxide (rGO) was first carried out
by a nucleophilic addition of n-butyllithium (n-BuLi) to rGO sheets, followed by
a subsequent coupling step of intermediates (n-Bu-rGO)n-Li(n+) with alkyl halide,
leading to functionalized rGO with controllable and reversible dispersiblity in
either nonpolar or polar solvents depending on the functional groups. Next, the
functional groups could be reversibly removed by solvothermal treatment to
generate reduced graphene sheets. Then the reduced materials could be again
functionalized using the same reaction sequence above with either the same or
different functional groups to almost the same extent of the first
functionalization cycle.
PMID- 26413618
TI - Electrostatically Gated Graphene-Zinc Oxide Nanowire Heterojunction.
AB - This paper presents an electrostatically gated graphene-ZnO nanowire (NW)
heterojunction for the purpose of device applications for the first time. A sub
nanometer-thick energy barrier width was formed between a monatomic graphene
layer and electrochemically grown ZnO NWs. Because of the narrow energy barrier,
electrons can tunnel through the barrier when a voltage is applied across the
junction. A near-ohmic current-voltage (I-V) curve was obtained from the graphene
electrochemically grown ZnO NW heterojunction. This near-ohmic contact changed to
asymmetric I-V Schottky contact when the samples were exposed to an oxygen
environment. It is believed that the adsorbed oxygen atoms or molecules on the
ZnO NW surface capture free electrons of the ZnO NWs, thereby creating a
depletion region in the ZnO NWs. Consequentially, the electron concentration in
the ZnO NWs is dramatically reduced, and the energy barrier width of the graphene
ZnO NW heterojunction increases greatly. This increased energy barrier width
reduces the electron tunneling probability, resulting in a typical Schottky
contact. By adjusting the back-gate voltage to control the graphene-ZnO NW
Schottky energy barrier height, a large modulation on the junction current
(on/off ratio of 10(3)) was achieved.
PMID- 26413619
TI - Synthesis and Characterization of the Graphene-Fe3O4 Hybrid Composite.
AB - Graphene and iron oxide composites have attracted huge attention in the fields of
nanoelectronics and nanodevices due to their superior magnetic and electric
characteristics. However, their synthesis methods are composed of many steps and
use toxic chemical reactants. Accordingly, in this study, a GN-Fe3O4 NP hybrid
composite was prepared using an eco-friendly and facile method. Its morphological
and structural characteristics were then investigated by scanning electron
microscopy, transmission electron microscopy, X-ray diffractometer and UV-visible
spectroscopy. The results indicated that the GN structures as well as Fe3O4 NPs
were significantly associated with the composite of GN-Fe3O4 NPs.
PMID- 26413620
TI - Functionalized Graphene Oxide with Hepatocyte Targeting as Anti-Tumor Drug and
Gene Intracellular Transporters.
AB - In order to realize the hepatocyte-specific targeted delivery of anti-tumor drug
and gene, lactosylated chitosan oligosaccharide (LCO) functionalized graphene
oxides (GO-LCO) containing quaternary ammonium groups (GO-LCO+) were prepared.
The formation and composition of GO-LCO+ were confirmed by FTIR, AFM, TGA and
zeta-potential. The in vitro cells uptakes of this functionalized GO were
investigated and the results showed that GO-LCO+ can deliver fluorescein FAM
labeled DNA sequence (FAM-DNA) into human hepatic carcinoma cells (QGY-7703) with
higher efficiency than positively charged chitosan oligosaccharide (CO)
functionalized graphene oxides (GO-CO+) without Lactose acid modification. The
loading efficiency of doxorubicin chloride (Dox) on GO-LCO+ with 477 ug/mg was
obtained at the initial Dox concentration of 0.45 mg/ml and release of Dox on GO
LCO+ showed strong pH dependence. The toxicity of GO-LCO+ before and after
loading with Dox toward QGY-7703 cells was further investigated. Our results
suggest the functionalized GO to be used as a nanocarrier for hepatocyte targeted
co-delivery of anti-tumor drugs and genes with low cytotoxicity, promising for
future applications in anticancer drug and gene combined therapy.
PMID- 26413621
TI - Inhibition of Viability of the Respiratory Epithelial Cells Using Functionalized
Graphene Oxide.
AB - The viability of A549 cells, a human lung carcinoma epithelial cell line, was
evaluated after exposure to graphene oxide (GO) and its derivatives (dodecylamine
GO (DA-GO), reduced GO (rGO), and sodium dodecyl sulfate rGO (SDS-rGO)). A
decrease in the relative amounts of C-OH bonds and an increase in the number of C
C and C-N bonds in the C 1s spectra indicated that the reduction of GO to rGO and
the surface functionalization of GO has taken place. The appearance of amine
stretching bands, out-of-plane C-H stretching vibrations, and S = O stretching
bands in the infrared spectra indicated the formation of DA-GO, rGO, and SDS-rGO,
respectively. Low concentrations (3-25 ug/mL) of GO, rGO, and SDS-rGO were found
to be mildly toxic, whereas DA-GO exhibited severe dose-dependent toxicity over
the same concentration range. High concen- trations (50-400 ug/mL) of GO and all
its derivatives resulted in severe toxicity to the A549 cells. It is believed
that surface functionality strongly affects the viability of A549 cells.
PMID- 26413622
TI - Three Arginine-Rich Cell-Penetrating Peptides Facilitate Cellular Internalization
of Red-Emitting Quantum Dots.
AB - Nanoparticles, such as semiconductor quantum dots (QDs), have been found
increasing use in biomedical diagnosis and therapeutics because of their unique
properties, including quantum confinement, surface plasmon resonance, and
superparamagnetism. Cell-penetrating peptides (CPPs) represent an efficient
mechanism to overcome plasma membrane barriers and deliver biologically active
molecules into cells. In this study, we demonstrate that three arginine-rich CPPs
(SR9, HR9, and PR9) can noncovalently complex with red light emitting QDs,
dramatically increasing their deliv- ery into living cells. Zeta-potential and
size analyses highlight the importance of electrostatic interactions between
positive-charged CPP/QD complexes and negative-charged plasma membranes
indicating the efficiency of transmembrane complex transport. Subcellular
colocalization indicates associations of QD with early endosomes and lysosomes
following PR9-mediated delivery. Our study demonstrates that nontoxic CPPs of
varied composition provide an effective vehicle for the design of optimized drug
delivery systems.
PMID- 26413623
TI - The Effect of Hydrophobin Protein on Conductive Properties of Carbon Nanotube
Field-Effect Transistors: First Study on Sensing Mechanism.
AB - Hydrophobin is a surface active protein having both hydrophobic and hydrophilic
functional domains which has previously been used for functionalization and
solubilization of graphene and carbon nanotubes. In this work, field-effect
transistors based on single nanotubes have been employed for electronic detection
of hydrophobin protein in phosphate buffer solution. Individual nanotubes, single
and multiwalled, are characterized by atomic force microscopy after being
immersed in protein solution, showing a relatively dense coverage with
hydrophobin. We have studied aspects such as nanotube length (0.3-1.2 um) and the
hysteresis effect in the gate voltage dependent conduction. When measured in
ambient condition after the exposure to hydrophobin, the resistance increase has
a strong dependence on the nanotube length, which we ascribe to mobility
degradation and localization effects. The change could be exceptionally large
when measured in-situ in solution and at suitable gate voltage conditions, which
is shown to relate to the different mechanism behind the hysteresis effect.
PMID- 26413624
TI - Differential Expression of Mir-1 26 and Vascular Endothelial Growth Factor in
Retinal Cells of Metabolic Acidosis-Induced Neonatal Rats.
AB - In present study, we aimed at investigating the expression level of microRNA and
the related gene which might be involved in retinopathy of prematurity. Neonatal
SD rats were randomly divided into 2 groups, the first one having rats with NH4CI
induced acidosis, as experimental group. We observed retinal vascular morphology
and hyperplasia using microscope, for both experimental and control groups, in
days 3, 5, 8, 10, 13 and 20 after birth. Total RNA from the retinal samples was
obtained at each time point. MiR-126 and VEGF mRNA were measured by quantitative
RT-PCR, while immunohistochemistry was applied to analyze the protein expression
level of VEGF. Results showed significant differential expression of miR-126 in
the acidosis-induced neonatal rats at day 8 when compared with control rats. The
VEGF mRNA and protein quantitative results also demonstrated corresponding
differential expression among the experimental and control groups. Results from
this study revealed that VEGF mRNA and protein expression levels increased in day
10, while the expression of miR-126 was remarkably down-regulated. It is thus
suggested that the miR-126 plays an important role in the development of acidosis
induced retinopathy.
PMID- 26413625
TI - Effect of Radix Trichosanthis and Trichosanthin on Hepatitis B Virus in
HepG2.2.15 Cells.
AB - Radix Trichosanthis is a Chinese herbal medicine that has great medical value and
pharmacological actions. There is already a long history of using the plant Radix
Trichosanthis as treatment for hepatitis B virus in China. This research mainly
focused on investigating the therapeutic effect of different extracts from Radix
Trichosanthis on hepatitis B virus, on a cellular level (ex vivo). Cell survival
rate of HepG2.2.15 cells was detected by MTT assay. HBsAg and HBeAg in HepG
2.2.15 cell supernatant were evaluated by enzyme linked immunosorbent assay
(ELISA). Results showed that water extract from Radix Trichosanthis had a
stronger inhibitive effect on expression of HBsAg and HBeAg in HepG2.2.15 cells
than the alcohol extract from the same plant. Considering that the most active
component of Radix Trichosanthis was in its aqueous extract and this might be
related to the active component Trichosanthin. Trichosanthin was further used for
related experiments to confirm this hypothesis. The results showed that
Trichosanthin, in the aqueous extract from Radix Trichosanthis, is likely the
main component responsible for the anti-hepatitis B viral effect.
PMID- 26413626
TI - Kinetics of Ultrasonic Drug Delivery from Targeted Micelles.
AB - To minimize the adverse side effects of conventional chemotherapy, a targeted
micellar drug carrier was investigated that retains hydrophobic drugs in its core
and then releases the drug via ultrasonic activation. This paper compares the
percent drug release from folated versus non-folated micelles by insonation at 70
kHz and different acoustic power densities. The encapsulated drug is Doxoru-
bicin (Dox). A physical model of zero-order release with first-order re
encapsulation was used to fit the experimental kinetic data. Additionally, the
acoustic activation power density and Gibbs free energy were introduced and
calculated for folated and non-targeted micelles. The data suggests an important
role of inertial cavitation in drug release and the presence of a power density
threshold for inertial cavitation.
PMID- 26413628
TI - Atmospheric-Pressure Plasma Interaction with Soft Materials as Fundamental
Processes in Plasma Medicine.
AB - Molecular-structure variation of organic materials irradiated with atmospheric
pressure He plasma jet have been investigated. Optical emission spectrum in the
atmospheric-pressure He plasma jet has been measured. The spectrum shows
considerable emissions of He lines, and the emission of O and N radicals
attributed to air. Variation in molecular structure of Polyethylene terephthalate
(PET) film surface irradiated with the atmospheric-pressure He plasma jet has
been observed via X-ray photoelectron spectroscopy (XPS) and Fourier transform
infrared spectroscopy (FT-IR). These results via XPS and FT-IR indicate that the
PET surface irradiated with the atmospheric-pressure He plasma jet was oxidized
by chemical and/or physical effect due to irradiation of active species.
PMID- 26413627
TI - Toxicity of Raw and Purified Single-Walled Carbon Nanotubes in Rat's Lung
Epithelial and Cervical Cancer Cells.
AB - The increased applications of carbon nanotubes in the field of drug delivery,
bioimaging and biosensors demand nanotubes to be of highest purity, free from
metallic impurities and amorphous carbon. All of these sectors require a profound
investigation about the toxic effects on human and the environment. Many attempts
have been made to purify and surface modify the carbon nanotubes, however a
detailed study on the raw and purified material has yet to be conducted. Here we
present the toxicity studies of raw and the purified single-walled carbon
nanotubes in rat's lung epithelial cell and cervical cancer cells (HeLa). These
cells were treated with increasing concentration of 0.5 ug/mL to 50 ug/mL and the
various biocompatibility assays were performed. The results showed an increased
cell death with purified single-walled carbon nanotubes followed by the depletion
of antioxidant levels and activation of the caspase cascade at a rapid rate
compared to raw single-walled carbon nanotubes. This suggests that purified
single walled carbon nanotubes are more toxic to the cells and exhibit ultra-fine
particulate matter like toxicity.
PMID- 26413629
TI - Plasma Interaction with Organic Molecules in Liquid as Fundamental Processes in
Plasma Medicine.
AB - Investigation of plasma-organic materials interaction in aqueous solution with
atmospheric pressure plasmas have been carried out. Degradation of methylene blue
(MB) in aqueous solution via atmospheric pressure He plasma exposure through
gas/liquid interface have been investigated. The optical emission spectrum shows
considerable emissions of He lines and the emission of O, OH and N radicals
attributed to dissociation of water (H2O) and air has been confirmed. Structure
variation of MB in solution treated with the atmospheric-pressure He plasma has
been measured by Fourier transform infrared spectroscopy (FT-IR). The results
obtained from FT-IR analysis show degradation of MB in solution treated with the
atmospheric-pressure He plasma. The pH effect of MB degradation was investigated
using controlled pH solutions by an ultraviolet-visible (UV-Vis) spectroscopy and
FT-IR. The results show no effect of MB degradation on pH. The results exhibit
that the atmospheric pressure plasmas exposure has made it possible to degrade
organic materials in solution due to irradiated radicals from plasma through
plasma/liquid interface.
PMID- 26413630
TI - Integration of Peptides for Enhanced Uptake of PEGylayed Gold Nanoparticles.
AB - Polyethylene glycol (PEG) has promoted the prospective applications of
nanoparticles (NPs) in cancer therapy. PEG is used to evade the immune system
allowing NPs accumulation within the tumor using its leaky vasculature. However,
the cellular uptake of PEG-coated (PEGylated) NPs is lower in comparison to non
PEGylated NPs since PEG minimizes surface binding of ligands that mediate NP
endocytosis. For improved outcome in therapeutic applications, it is necessary to
enhance the uptake of PEGylated NPs. We added a peptide containing an integrin
binding domain known as the RGD sequence to the NP surface in addition to PEG. We
used gold NPs (GNPs) of sizes 14, 50, and 70 nm in this study. Our in vitro data
for HeLa cells show enhanced uptake for NPs coated with both PEG and the peptide
in comparison to PEGylated GNPs. NPs of size 50 nm had the highest uptake among
the three sizes for all GNP surfaces. A similar size-dependent trend was observed
for MDA-MB-231 cells for as-made GNPs with lower uptake in comparison to HeLa
cells. However, only 14 nm peptide-modified PEGylated NPs had enhanced uptake.
Hence, NP uptake was found dependent on cell type and NP surface properties. A
properly designed NP system with both PEG and cell membrane targeting peptides
can be used to protect it from the immune system and promote internalization by
cells upon entry into tumor environment.
PMID- 26413631
TI - Differentially Expressed miRNA in Inflammatory Mucosa of Chronic Rhinosinusitis.
AB - Chronic sinusitis (chronic rhinosinusitis, CRS) is a chronic inflammatory disease
of the nasal cavity and paranasal sinuses, pathogenesis of which is not yet
completely elucidated. MicroRNA has been shown to extensively be involved in
immune response. To analyze the differential expression of miRNAs in chronic
sinusitis, with or without nasal polyps (nasal polyps, NP), seven miRNAs (miR-
181b, miR-26b, miR-155, miR-146a, miR-125b, miR-124 and miR-92a) that are
associated with inflammation were selected to be quantifying by RT-qPCR in 40
clinical samples and 5 controls. When compared to the normal control group,
results showed that, in all patients with CRS, miR- 125b, miR-155 and miR-146a
were up-regulated (P < 0.05), while miR-92a, miR-26b and miR- 181b were down
regulated (P < 0.05). MiR124 expression levels were not found to have significant
changes. In relation to CRS without NP, miR-125b and miR-155 were significantly
up-regulated while miR-92a, miR-26b, miR-181b were down-regulated in NP patients.
Furthermore, the miR-92a and miR-26b expression levels were significantly reduced
while miR-146a and miR124 expression levels had no significant changes in the NP
samples. The RT-qPCR results indicate that the miRNAs were differentially
expressed in CRS patients and various inflammation severities could lead to this
difference. The results from this study may further reveal the relationship
between miRNA expressions and inflammation. These results can also provide an
important mechanism (primitive data) on the occurrence of chronic sinusitis and
nasal polyps.
PMID- 26413632
TI - Copper Oxide Nanoparticles Reduce Vasculogenesis in Transgenic Zebrafish Through
Down-Regulation of Vascular Endothelial Growth Factor Expression and Induction of
Apoptosis.
AB - The present study investigated the effects of exposure to metal oxide
nanoparticles on vasculogenesis/angiogenesis using transgenic zebrafish. The
study also examined the potential mechanisms involved in those effects using
human umbilical vein endothelial cells (HUVEC). TG (nacre/fli1:EGFP) zebrafish
were exposed to nano-sized titanium dioxide (TiO2), silica dioxide (SiO2), and
copper oxide (CuO) particles at 0.01, 1 and 100 ug/ml concentrations from 1 to 5
dpf (day-post-fertilization). Angiogenesis was evaluated morphologically at the
end of exposure. Exposure to CuO nanoparticles reduced the number of transversely
running subintestinal vessels in TG zebrafish. Exposure to CuO nanoparticles down
regulated the expression of vascular endothelial growth factor (VEGF) and VEGF
receptor in endothelial cells sorted by Fluorescence Activated Cell Sorter
(FACS). Exposure of HUVEC to CuO nanoparticles reduced cell viability and
increased apoptotic index in a dose-dependent manner. The results suggested that
CuO nanoparticles inhibit vasculogenesis through reduction of VEGF expression and
induction of apoptosis.
PMID- 26413633
TI - Polyethylene Films Containing Silver Nanoparticles for Applications in Food
Packaging: Characterization of Physico-Chemical and Anti-Microbial Properties.
AB - This paper reports the antibacterial effect and physico-chemical characterization
of films containing silver nanoparticles for use as food packaging. Two
masterbatches (named PEN and PEC) con- taining silver nanoparticles embedded in
distinct carriers (silica and titanium dioxide) were mixed with low-density
polyethylene (LDPE) in different compositions and extruded to produce plain
films. These films were characterized by Scanning Electron Microscopy (SEM), X
ray diffraction (XRD), Differential Scanning Calorimetry (DSC), Thermogravimetric
analysis (TGA) and Fourier Transform Infrared Spectroscopy (FTIR). The morphology
of the films showed the formation of agglomerates of nanoparticles in both PEN
and PEC composites. X-ray analyses confirmed the presence of SiO2 in PEN samples
and TiO2 in PEC samples. Thermal analyses indicated an increase in thermal
stability of the PEC compositions. The antimicrobial efficacy was determined by
applying the test strain for Escherichia coli and Staphylococcus aureus,
according to the Japanese Industrial Standard Method (JIS Z 2801:2000). The films
analyzed showed antimicrobial properties against the tested microorganisms,
presenting better activity against the S. aureus than E. Coli. These findings
suggest that LDPE films with silver nanoparticles are promising to provide a
significant contribution to the quality and safety of packaged food.
PMID- 26413634
TI - Copper Phthalocyanine Functionalized Single-Walled Carbon Nanotubes: Thin Films
for Optical Detection.
AB - Thin films of non-covalently hybridized single-walled carbon nanotubes (SWCNT)
and tetra-substituted copper phthalocyanine (CuPcR4) molecules have been produced
from their solutions in dimethylformamide (DMF). FTIR spectra revealed the 7pi
7pi interaction between SWCNTs and CuPcR4 molecules. DC conductivity of films of
acid-treated SWCNT/CuPcR4 hybrid has increased by more than three orders
of.magnitude in comparison with conductivity of CuPcR4 films. Scanning electron
microscopy (SEM) and atomic force microscopy (AFM) measurements have shown that
films obtained from the acid-treated SWCNTs/CuPcR4 hybrids demonstrated more
homogenous surface which is ascribed to the highly improved solubility of the
hybrid powder in DMF Using total internal reflection ellipsometry spectroscopy
(TIRE), thin films of the new hybrid have been examined as an optical sensing
membrane for the detection of benzo[a]pyrene in water to demonstrate the sensing
properties of the hybrid.
PMID- 26413635
TI - Subband Structure and Effective Mass in the Inversion Layer of a Strain Si-Based
Alloy P-Type MOSFET.
AB - In this paper, the subband structure and effective mass of an Si-based alloy
inversion layer in a PMOSFET are studied theoretically. The strain condition
considered in our calculations is the intrinsic strain resulting from growth of
the silicon-carbon alloy on a (001) Si substrate and mechanical uniaxial stress.
The quantum confinement effect resulting from the vertically effective electric
field was incorporated into the k . p calculation. The distinct effective mass,
such as the quantization effective mass and the density-of-states (DOS) effective
mass, as well as the subband structure of the silicon-carbon alloy inversion
layer for a PMOSFET under substrate strain and various effective electric field
strengths, were all investigated. Ore results show that subband structure of
relaxed silicon-carbon alloys with low carbon content are almost the same as
silicon. We find that an external stress applied parallel to the channel
direction can efficiently reduce the effective mass along the channel direction,
thus producing hole mobility enhancement.
PMID- 26413636
TI - A Resultant Stress Effect of Contact Etching Stop Layer and Geometrical Designs
of Poly Gate on Nanoscaled nMOSFETs with a Si1-xGe(x) Channel.
AB - In this research, an n-type metal-oxide-semiconductor field effect transistor
(nMOSFET) device with a SiGe channel exerted by the combination of a contact
etching stop layer (CESL) and silicon germanium (Si1-xGe(x)) channel stressors is
proposed. To explore the foregoing mechanical effect on the stress distribution
of nMOSFETs within the channel region, a process-oriented simulated technique is
adopted for the concerned nMOSFET device. The loading sources are a 1.1 GPa
tensile CESL (t-CESL) and a SiGe channel structure constructed with 0%, 22.5%,
and 25%, germanium (Ge) mole fractions. The results of the simulation show that
the stress components of the Si1-xGe(x) channel evidently increase when the Ge
mole fraction within a Si1-xGe(x) layer is increased. A pulling force exerted on
the protruding gate structure by the CESL layer that causes dominant bending
deformation and channel stress variation behaviors is a major reason for this
phenomenon. Therefore, the degree of bending effect caused by the protruding gate
structure is concluded as being the key to determining the trends and stress
magnitudes of the Si1-xGe(x) device channel.
PMID- 26413637
TI - Structural Optimizations of Silicon Based NMOSFETs with a Sunken STI Pattern by
Using a Robust Stress Simulation Methodology.
AB - As the strained engineering technology of metal-oxide-semiconductor field effect
transistors (MOSFET) is scaled beyond the 22 nm node critical dimension, shallow
trench isolation (STI) becomes one of the most important resolutions for isolate
devices to enhance the carrier mobility of advanced transistors. Several key
design factors of n-type MOSFET (NMOSFET) under the resultant loadings of STI
structures and contact etching stop layers are sensitively analyzed for silicon
channel stress via finite element method-based simulations integrated with the
use of design of experienmnts. NMOSFETs with 15 nm deep sunken STI have achieved
a ~5% mobility enhancement as compared with a regular STI shape. By adopting
simulation-based factorial designs, we have determined that the design factor of
recess depth in STI is a critical factor influencing device performance.
Moreover, a response surface curve on carrier mobility of NMOSFET under a
consideration of combining the sunken STI and source/drain lengths is further
presented in this research.
PMID- 26413638
TI - Annealing Dependence of Solution-Processed Ultra-Thin ZrOx Films for Gate
Dielectric Applications.
AB - Ultra-thin ZrOx thin films on Si substrates were prepared by sol-gel technique
and processed with different methods (baked on hot plate at 150 degrees C,
annealed at 500 degrees C in furnace, and photo-annealed under UV light). The
decomposition of the organic groups and the formation of Zr-O bonding in the ZrOx
thin films were confirmed by Fourier transform infrared spectroscopy and X-ray
photoelectron spectroscopy. It is found that the ZrOx thin film annealed under UV
light shows decent characteristics, including an ultra-small surface roughness, a
low leakage current density of 10(-9) A/cm2 at 1 MV/cm, a large breakdown
electric field of 9.5 MV/cm, and a large areal capacitance of 775 nF/cm2.
PMID- 26413639
TI - Atmospheric-Pressure Gas-Breakdown Characteristics with a Radio-Frequency
Voltage.
AB - We present He atmospheric-pressure gas-breakdown phenomena with radio frequency
(RF) voltages in the frequency region from a few tens MHz to 100 MHz. The gas
breakdown voltage for RF and very high frequency (VHF) discharges is considerably
lower than that for the DC discharge, and the gas-breakdown voltage is
effectively reduced to be as low as 160 V in VHF region. The discharge
characteristics drastically change with increasing discharge-voltage frequency,
and strong emisson is highly loclized in front of the power- and ground-electrode
in the VHF discharges. The lowering gas-brakdown voltage and the localized
emission-profile are well explained by the effect of the charged-particle
confinement in a micro dishcarge-space.
PMID- 26413640
TI - Effects of Annealing on the Microstructures and UV and Visible Light-Induced
Photocatalytic Activities of Indium Hydroxide Nanocubes.
AB - This work initiated a systematic study on the thermal treatment for In(OH)3
photocatalysts and its impact on their microstructures and photocatalytic
properties. The phase transformation process from In(OH)3 to In2O3 was
investigated by XRD, TG, DRS and ion etching XPS technologies. The results
demonstrated that the formation of In2O3 phase occurred from surface to inside of
bulk In(OH)3 and a heterojunction structure between In2O3 and In(OH)3 was formed.
The variation of textural properties and the formation of heterojunction
structure were crucial for the enhanced UV-light photocatalytic activities for
RhB degradation, while the visible-light photocatalytic activity was mainly
associated with the enhancement of the visible light absorbance capacity deriving
from surfaced In2O3. The results may be extended to comprehend the structure
property correlations of hydroxide-containing photocatalysts and help to explore
highly efficient photocatalysts towards thermal decomposition.
PMID- 26413641
TI - Effect of Blend Composition on Binary Organic Solar Cells Using a Low Band Gap
Polymer.
AB - This report investigates the influence of the solution blend composition of
binary bulk heterojunction organic solar cells composed of poly(2,1,3
benzothiadiazole-4,7-diyl[4,4-bis(2-ethylhexyl)-4H- cyclopenta[2,1-b:3,4
b'dithiophene-2,6-diy]] (PCPDTBT) and [6,6]-phenyl C71 butyric acid methyl ester
(PC71BM). The blend polymer:fullerene composition was varied from 1:1 (50 wt%
PC71 BM) to 2:9 (82 wt% PC71 BM). Increasing the amount of polymer in the blend
results in the greatest overall absorption, as the donor material PCPDTBT is the
main contributor to absorption. However, high polymer content leads to poor
photovoltaic performance. For this material combination, the optimum blend
polymer:fullerene composition was found to be 2:7. Increasing the fullerene
content in the blend led to a significant improvement in the internal quantum
efficiency of devices. This was correlated with an increase of the electron
mobility, as the fullerene content was increased. Improved electron transport,
leading to more balanced transport between electrons and holes, significantly
improved the short circuit current density (Jsc) and fill factor (FF).
PMID- 26413642
TI - Fabrication and Characterization of Electronic and Optical Properties of
Polyaniline Nanopatterns.
AB - The authors conducted polyaniline (HA) polymerization on a micro-scale patterned
Si water and nano-scale patterned Al surface. Polymerization was performed using
a microliter solution droplet made of aniline, HCI and oxidation agent ammonium
peroxodisulfate (APS). The droplet was dropped on a flat Si wafer, a micro
patterned Si wafer and a nanostructured Al surface. The SEM image showed that PA
was densely polymerized on the circle edge of the dropped 1 mm sized droplet on
the flat Si wafer because of large surface tension due to the flat surface. On
the other hand, a droplet was broken on a circular trench pattern of 100 um in
diameter fabricated on a Si wafer. The width and depth of the trench were 1 um
and 1 um, respectively. Tree-like polymer was intensively polymerized along the
circular trench. Droplet was also dropped on a lattice trench pattern whose pitch
was 10 um. The width and the depth of the trench were 1 um and 1 um,
respectively. The SEM image showed that dots of PA were fabricated along the
trenches. Far smaller dots of PA were also observed on the flat area of the
lattice. Thus, micro-scale structure affects the shape and size of PA in
polymerization. Nanoscopic polymerization of PA was conducted locally in a
nanoscale highly-oriented line pattern with nanoscale trenches formed on an Al
surface. One of the characteristic fabricated patterns was a highly conductive PA
line pattern whose pitch was 100 nm. In this case, point-contact IV
characteristic measurement, step-like curve was observed. PL spectra of the PA
line-pattern exhibited significantly enhanced emission peaks at 380, 450 anc 550
nm due to PA which were overlapped by the rippled PL pattern due to the Al
nanostructure.
PMID- 26413643
TI - Numerical Study on the Particle Trajectory Tracking in a Micro-UV Bio
Fluorescence Sensor.
AB - A micro-UV bio-fluorescence sensor was developed to detect primary biological
aerosols including bacteria, bacterial spores, fungal spores, pollens, viruses,
algae, etc. In order to effectively detect the bio-particles in a micro-UV bio
fluorescence sensor, numerical calculations were performed to adjust for
appropriate flow conditions of the sensor by regulating the sample aerosols and
sheath flow. In particular, a CFD-based model of hydrodynamic processes was
developed by computing the trajectory of particles using commercially available
ANSYS CFX-14 software and the Lagrangian tracking model. The established model
was evaluated with regard to the variation of sheath flow rate and particle size.
Results showed that the sheath flow was changed rapidly at the end of nozzle tip,
but the sample particles moved near the center of aerosol jet for aerodynamic
focusing with little deviation from the axis.
PMID- 26413644
TI - Near Band Edge Emission by Free Exciton Decay and Intrinsic Ferromagnetic
Ordering of Cu-Doped SnO2 Hollow Nanofibers.
AB - High quality nanocrystalline pristine and Cu-doped SnO2 hollow nanofibers were
successfully prepared through simple and effective electrospinning technique.
Nanofibers calcined at 600 degrees C for 3 h were characterized with different
analytical techniques such as X-ray diffraction (XRD), Transmission electron
Microscope (TEM) and Vibrating sample magnetometer (VSM). Observed TEM images and
XRD patterns were corroborate to the formation of tetragonal crystalline SnO2
hollow nanofibers with rutile phase. Excellent optical behaviour was observed for
Cu-doped SnO2. Highly intense near band edge emission at 3.58 eV for Cu-doped
SnO2 evidences the free exciton decay process in the hollow nanofibers. For the
first time we have reported here the near band edge PL emission in Cu-doped SnO2
tubular hollow nanostructure. This study substantiates that material potential
for UV-lasing application. In addition to the above, magnetic measurement
ascribes that Cu-doped SnO2 exhibit the intrinsic room temperature ferromagnetism
within the low field strength. The occurrence of ferromagnetism in Cu-doped SnO2
is directly related to the p-d ferromagnetic exchange coupling between the local
magnetic moment of Cu2+ and the polarized valence electrons of surrounding
oxygen. Over all this study provides the primary information about tunable
multifunctionality of SnO2 hollow nanostructures by adding the non-magnetic Cu
ions.
PMID- 26413645
TI - Plasmonics Resonance Enhanced Active Photothermal Effects of Aluminum and Iron
Nanoparticles.
AB - Localized Surface Plasmonics Resonance (LSPR) enhanced active photothermal
effects of both aluminum nanoparticles (Al NPs) and iron nanoparticles (Fe NPs)
are experimentally observed. Photothermally activated motion and ignition by low
energy xenon flash are quantitatively measured. For nanoparticles of comparable
sizes, photothermally activated motion height of Fe NPs is about 60% lower than
that of Al NPs, while photothermal Minimum Ignition Energy (MIE) of Fe NPs is
about 50% lower than that of Al NPs. Joule heating by LSPR enhanced photothermal
effects among nanoparticles and subsequently triggered oxidation reactions are
found responsible for the motion and ignition of the nanoparticles.
PMID- 26413646
TI - Boron Doped Nanocrystalline Film with Improved Work Function as a Buffer Layer in
Thin Film Silicon Solar Cells.
AB - We investigated thin film silicon solar cells with boron doped hydrogenated
nanocrystalline silicon/ hydrogenated amorphous silicon oxide [p-type nc-Si:H/a
SiOx:H] layer. First, we researched the bandgap engineering of diborane (B2H6)
doped wide bandgap hydrogenated nanocryslline silicon (p-type nc-Si:H) films,
which have excellent electrical properties of high dark conductivity, and low
activation energy. The films prepared with lower doping ratio and higher hydrogen
dilution ratio had higher optical gap (Eg), with higher dark conductivity
(sigma(d)), and lower activation energy (Ea). We controlled Eg from 2.10 eV to
1.75 eV, with sigma(d) from 1.1 S/cm to 7.59 x 10(-3) S/cm, and Ea from 0.040 eV
to 0.128 eV. Next, we focused on the fabrication of thin film silicon solar
cells. By inserting p-type nc-Si:H film into the thin film silicon solar cells,
we achieved a remarkable increase in the built-in potential from 0.803 eV to
0.901 eV. By forming p-type nc-Si:H film between SnO2:F/ZnO:Al (30 nm) and p-type
a-SiOx:H layer, the solar cell properties of open circuit voltage (Voc), short
circuit current density (Jsc), and efficiency (eta) were improved by 3.7%, 9.2%,
and 9.8%, respectively.
PMID- 26413647
TI - Investigation of Electrical and Optical Properties of Highly Transparent
TCO/Ag/TCO Multilayer.
AB - Transparent conductive oxides (TCOs) have been widely used as transparent
electrodes for opto-electronic devices, such as solar cells, flat-panel displays,
and light-emitting diodes, because of their unique characteristics of high
optical transmittance and low electrical resistivity. Among various TCO
materials, zinc oxide based films have recently received much attention because
they have advantages over commonly used indium and tin-based oxide films. Most
TCO films, however, exhibit valleys of transmittance in the wavelength range of
550-700 nm, lowering the average transmittance in the visible region and
decreasing short-circuit current (Isc) of solar cells. A TCO/Ag/TCO multi-layer
structure has emerged as an attractive alternative because it provides optical
characteristics without the valley of transmittance compared with a 100-nm-thick
single-layer TCO. In this article, we report the electrical, optical and surface
properties of TCO/Ag/TCO. These multi-layers were deposited at room temperature
with various Ag film thicknesses from 5 to 15 nm while the thickness of TCO thin
film was fixed at 40 nm. The TCO/Ag/TCO multi-layer with a 10-nm-thick Ag film
showed optimum transmittance in the visible (400-800 nm) wavelength region. These
multi-layer structures have advantages over TCO layers of the same thickness.
PMID- 26413648
TI - Synthesis and Electrochemical Properties of LiFePO4/C for Lithium Ion Batteries.
AB - LiFePO4/C was prepared through a facile rheological phase reaction method by
using Fe3(PO4)2, Li3PO4 . 8H2O, and glucose as reactants. The LiFePO4/C samples
were characterized by X-ray diffraction, scanning electron microscopy, and
thermogravimetric analysis. The electrochemical properties of the samples were
investigated. The results show that the LiFePO4/C samples have single-phase
olivine-type structure, and their particles feature a spherical shape. The carbon
coating on the particles of LiFePO4 is about 1.8% of the LiFePO4/C by weight. The
particle size was distributed from 0.2 to 1 um. The initial discharge capacity of
LiFePO4/C reached 154 mA h/g at 0.1 C. The retained discharge capacity of
LiFePO4/C was 152.9 mA h g(-1) after 50 cycles. The LiFePO4/C also showed better
cycling performance than that of the bare LiPeO4 at a higher charge/discharge
rate (1 C). The LIFePO4/C prepared in this way could be a promising cathode
material for lithium ion battery application.
PMID- 26413649
TI - Catalytic Performance of La0.8K0.2Fe0.7Mn0.3O3 with Pt-Substitution in B-Site for
Removal of NOx and Soot.
AB - Nanocrystalline, porous, perovskite La0.8K0.2Fe0.69Mn0.3Pt0.01O3,
La0.8K0.2Fe0.67Mn0.3Pt0.03O3, La0.8K0.2Fe0.65Mn0.3Pt0.05O3 catalysts were
prepared by the citrate-gel process. The optimized chemical composition
La0.8K0.2Fe0.67Mn0.3Pt0.03O3 has a porous structure and it shows a good activity
for soot combustion, with T20, T50 and T90 being 149, 367 and 409 degrees C,
respectively. Furthermore, the La0.8K0.2Fe0.67Mn0.3Pt0.03O3-coated honeycomb
ceramic device was prepared by the citrate-gel assisted dip-coating process and
it has the effect of simultaneous removal of diesel soot and nitrogen oxides at
the operational temperature range of 200 to 400 degrees C, with a NOx maximum
conversion rate of 21.2%. It seems that the perovskite structure benefits the
activity of low Pt content due to higher contribution of lattice oxygen and local
changes in redox reaction.
PMID- 26413650
TI - Synthesis and Characterization of Polyvinylpyrrolidone Silica Core-Shell
Nanocomposite Particles.
AB - In this work, a novel and facile strategy for making a new type of polymer/silica
nanocomposte particle was proposed. Colloidally stable polyvinypyrrolidone
(PVP)/silica core-shell nanocomposite particles have been successfully
synthesized using an azo initiator via seed polymerization of N-vinyl-2
pyrrolidone (NVP) and VFSs (VFSs) that were derived from vinyl triethoxysilane
(VTES). It was suggested from the FTIR and TGA analysis that the copolymerization
reaction of NVP with VFSs has been thoroughly carried out. In addition, SEM
images showed that PVP/silica nanocomposite particles have relatively rough
surface due to surface polymerization in comparison with VFSs. Furthermore, TEM
results proved that the size of VFSs had considerable effects on the appearance
of PVP/silica nanocomposite particles. Generally, it presented that several
silica nanoparticle cores with an average size of 78 nm mainly pack together
within each nanocomposite particle after seed polymerization. Interestingly, the
average shell thickness was 59 nm for most PVP/silica nanocomposite particles
with cores about 242 nm. However, when the core size was large enough to about
504 nm, a series of PVP/silica nanocomposite particles with a relative thin shell
were observed.
PMID- 26413651
TI - Indium Tin Oxide Nanoparticles/Vaseline Nanocomposites: Preparation of
Nanoelectrode Assembles with Tunable Dimensions.
AB - In this paper, we describe a novel approach for fabricating tailor-made indium
tin oxide nanoelectrode assembles (ITO-NEAs) based on indium tin oxide
nanoparticles (ITONPs) as conducting materials and vaseline as insulating binder.
ITO nanoelectrode assembles were formed on the surface of a glassy carbon
electrode (GCE) by uniformly covering GCE with ITONPs/vaseline nanocomposite.
Cyclic voltammetry (CV) studies demonstrated that the ITO-NEAs exhibit fast mass
transport and low charging current, suggesting that the ITO-NEAs, fabricated with
ITONPs and vaseline hybrid film coating, behave like a microelectrode array.
Furthermore, electrochemical results show the as-prepared ITONPs electrodes have
tunable dimensions, ranging from a conventional electrode to a nanoelectrode
ensemble, depending on the amount of insulting vaseline dissolved in the ITO
NPs/acetone dispersion. As novel kind of ITONPs-based film electrodes with
tunable dimensions and good electrochemical activity, the ITO film electrodes are
very attractive for potential application in fundamental and practical
electrochemical studies.
PMID- 26413652
TI - Field Emission from Zinc Oxide Nanobelts.
AB - We report here, the in-situ field emission (FE) property measurement on the
individual ZnO nanobelts inside a high resolution transmission electron
microscope (TEM) using a special scanning tunneling microscopy (STM)-TEM system.
The field emission properties were found to be size scale dependent. It was found
that the threshold voltage decreases and the field enhancement factor increases
with the decrease in the diameter of the tip of the nanobelt and increase in the
sharpness of the tip. The field emission parameter was estimated following the
Fowler-Nordheim (F-N) theory. The ZnO nanobelt with the sharp agave like tip
structure (d = 10 nm) showed the highest value of the field enhancement factor,
beta ~ 4562, and a high field emission current of ~ 502 uA.
PMID- 26413653
TI - High-Temperature Cross-Linking of Carbon Nanotube Multi-Yarn Using
Polyvinylpyrrolidone as a Binding Agent.
AB - Carbon nanotube (CNT) multi-yarn was cross-linked together at elevated
temperatures using a poly- mer, with the intent of improving their strength and
electrical conductivity. They were functionalized using an acid treatment and
immersed in a bath of different concentrations (0.5%, 0.1%, and 0.2%) of
polyvinylpyrrolidone (PVP). Then they were placed in an oven at various
temperatures (180 degrees C, 200 degrees C, and 220 degrees C) in order to
cause cross-linking among the carbon nanotube yarns. The phys- ical, chemical,
electrical, and mechanical properties of the cross-linked yarns were
investigated. The yarns cross-linked at higher temperatures and greater
concentrations of PVP had a greater increase in linear mass density, indicating
that the cross-linking process had worked as expected. Yarns that were cross
linked at lower temperatures had greater tensile strength and better spe- cific
electrical conductivity. Those that were treated with a greater concentration of
polymer had a greater ultimate tensile strength. All these results are
encouraging first step, but still need further development if CNT yarn is to
replace copper wire.
PMID- 26413654
TI - Spectroscopic Characteristics of Three Dimensional Split-Ring Resonator Arrays at
Terahertz Frequencies.
AB - In this work, three-dimensional, stacked arrays of subwavelength, square, dual,
concentric split ring resonators exhibiting characteristics at the Terahertz
frequencies have been designed, simulated, and fabricated through a
photolithographic lift-off process and electron beam evaporation metal
deposition. Characterization of the split-ring resonator arrays was performed by
transmission mode Terahertz time domain spectroscopy. The effects of the split
ring resonator unit cell spatial dimensions on resonant absorption frequencies
and relative absorption strength are investigated as well as effects from the
addition of a dielectric spacing layer and additional split-ring resonator layer.
The split-ring resonator arrays were seen to develop two distinct and switchable
LC resonances as well as a dipole resonance by measuring the arrays at 0 degrees
and 90 degrees in-plane rotations about the terahertz propagation vector. The
dielectric spacing layer served to effectively lower the resonant frequencies of
the split-ring resonantors while the dual split-ring resonator array was seen to
have a slight modulating effect on the absorption strength at the resonant
frequencies compared to that of the passivated array without the second layer.
PMID- 26413655
TI - Crystalline Fraction and Doping Concentration Effect on Heterojunction Solar
Cells n-Doped uc-Si:H Back Surface Field Layer.
AB - The back surface field (BSF) plays a vital role for high efficiency in the
Heterojunction Intrinsic Thin (HIT) film solar cell. This paper investigated the
effect of crystalline volume fraction (Xc) and 1% hydrogen diluted phosphine
(PH3) gas doping concentration of the n-type uc-Si:H back surface file (BSF)
layer. Initially, the thickness of the n-type uc-Si:H BSF layer was optimized.
With increase in Xc from 6% to 59%, the open circuit voltage (Voc) increased from
573 mV to 696 mV, and the fill factor (FF) also increased from 59% to 71%. In the
long wavelengths region (>= 950 nm), the QE of the solar cells decreased over the
optimized Xc of the n-doped micro BSF layer, due to the defects of a film. In the
second part of this paper, the effect of high conductivity n-type uc-Si:H BSF
layer with optimized thickness on the performance of HIT solar cells was
investigated, by doping gas ratio variation. Even though Xc decreased,
conductivity was increased, with increasing PH3 doping concentration. Under the
optimized condition, a n-uc-Si:H BSF layer has a dark conductivity of 2.59 S/cm,
activation energy of 0.0519 eV, and X, of 52%. The conversion efficiency of 18.9%
was achieved with a Voc of 706 mV, fill factor of 72%, and short circuit current
density of 37.1 mW.cm(-2).
PMID- 26413656
TI - Microwave Band-Pass Filter with Aerosol-Deposited Al2O3-Polytetrafluoroethylene
Composite Thick Films.
AB - Fabrication of microwave band-pass filter with coplanar waveguide with ground
structure was realized by employing Al2O3-polytetrafluoroethylene (Al2O3-PTFE)
composite thick films for integrated substrates produced by aerosol deposition
(AD). In order to predict the performance of the band-pass filter, 3-D
electromagnetic simulations were performed by high-frequency structure analysis.
The thick Al2O3-PTFE composite films prepared by the AD process had submicron
sized Al2O3 crystallites due to the shock-absorbing effect of PTFE during the
film growth. The thick films were characterized by X-ray diffraction and scanning
electron microscopy. The Cu transmission lines with the thickness of 300 nm were
deposited by electron-beam evaporation to form the band-pass filter. The
fabricated band-pass filter showed similar characteristics to the simulation
results. The insertion loss and resonance frequency were 9.5 dB and 2.3 GHz,
respectively.
PMID- 26413657
TI - Preparation and Phase Transfer of Hydrophobic CdSe-Based Quantum Dots.
AB - Monodispersed CdTe(x)Se1-x and CdSe cores were synthesized via organic methods.
The as-prepared cores were coated with a Cd(y)Zn1-yS shell by an epitaxial
growth. Compared with the cores, an obvious red shift was observed in both the
absorption and photoluminescence (PL) spectra of core-shell quantum dots (QDs)
and the PL efficiency was improved. The CdSe-based core-shell QDs were
transferred from oil to water phase by the encapsulation of amphiphilic polymers.
The ligands of QDs, namely hexadecylamine (HDA) and oleic acid (OA), dramatically
influenced the process of phase transfer. The process of phase transfer of HDA
coated CdTe(x)Se1-x/CdyZn1-yS core-shell QDs was failed, however, the OA-coated
CdSe/CdyZn1-yS core-shell QDs can be successfully transferred from oil to water
phase. This is ascribed that the surface ligand HDA falls from CdTe(x)Se1
x/Cd(y)Zn1-yS core-shell QDs during the process of phase transfer, leading to non
interaction between QDs and amphiphilic polymers. The effect of molecular weight
of the poly(styrene-co-maleic anhydride) (PSMA) on the phase transfer was also
investigated. For the QDs with the same size, the PSMA with high molecular weight
exhibit a shorter time in the process of phase transfer compared with light
molecular weight. Furthermore, the size of the QDs also affects the process of
the phase transfer from oil to water phase. The smaller of the QDs, the shorter
of the phase transfer time.
PMID- 26413658
TI - Viscoelastic Properties of Poly[(butylene succinate)-co-adipate] Nanocomposites.
AB - This article reports the viscoelastic properties of poly[(butylene succinate)-co
adipate] (PBSA) nanocomposites. The nanocomposites of PBSA with various loadings
of organically modified clay were prepared by melt-mixing in a batch-mixer. The
solid and melt-state viscoelastic properties of neat PBSA and various
nanocomposites were studied in detail. The dynamic mechanical studies
demonstrated an increase in the storage modulus of PBSA matrix with organoclay
loading. Melt-state rheological properties were found to be modified with
organoclay loading changing from liquid-like, to gel-like and then viscoelastic
solid-like. Such changes in viscoelastic properties along with the improvements
in thermomechanical properties are expected to open opportunities for the use of
PBSA extending its applications from the classical field of packaging to new
niches such as tissue-engineering.
PMID- 26413659
TI - Selective Laser Direct Patterning of Silver Nanowire Percolation Network
Transparent Conductor for Capacitive Touch Panel.
AB - We introduce a facile method to enhance the functionality of a patterned metallic
transparent conductor through selective laser ablation of metal nanowire
percolation network. By scanning focused nanosecond pulsed laser on silver
nanowire percolation network, silver nanowires are selectively ablated and
patterned without using any conventional chemical etching or photolithography
steps. Various arbitrary patterns of silver nanowire transparent conductors are
readily created on the percolation network by changing various laser parameters
such as repetition rate and power. The macroscopic optical and electrical
properties of the percolation network transparent conductor can be easily tuned
by changing the conductor pattern design via digital selective laser ablation.
Further investigation on the silver nanowire based electrode line prepared by the
ablation process substantiates that the general relation for a conducting thin
film fails at a narrow width, which should be considered for the applications
that requires a high resolution patterns. Finally, as a proof of concept, a
capacitive touch sensor with diamond patterns has been demonstrated by selective
laser ablation of metal nanowire percolation network.
PMID- 26413660
TI - Dynamic Properties of Helium Atmospheric Dielectric-Barrier-Discharge Plasma Jet.
AB - We present here experiments on helium atmospheric dielectric-barrier discharge
jet in open air. A long stable plasma plume is realized at high applied voltage
and high gas flow rate. Optical emission measurements show that the plasma plume
consists of two part: a plume head with high energy electrons and a tail part
with low energy electrons. The plasma plume propagates away from the quartz-tube
outlet with about 30-80 km/sec along the helium gas flow channel. The propagation
velocity of plasma plume is in the time scale of electron drift velocity, and the
electric field plays an important role as a driving force of the plasma plume
propagation.
PMID- 26413661
TI - Dielectric Properties of (Ca0.7Sr0.3)(Zr0.8Ti0.2)O3 Thin Films with Different
Deposition Temperatures.
AB - In this paper, (Ca0.7Sr0.3)(Zr0.8Ti0.2)O3 thin films were fabricated by RF
sputtering at various deposition temperatures from 300 degrees C to 700 degrees
C to determine the optimal deposition condition. The XRD data confirmed the
successful fabrication of crystalline CSZT thin films. Based on the dielectric
properties of the fabricated thin films, the optimal deposition temperature was
700 degrees C, which resulted in a film with a relatively high dielectric
constant and low dielectric loss (28.4 and 0.006) (at 1 MHz). Moreover, the CSZT
thin film deposited at 700 degrees C showed stable dielectric properties at
microwave frequencies. With increasing deposition temperature, the roughness of
the CSZT thin film increased but the leakage current of the CSZT thin film
decreased, simultaneously.
PMID- 26413662
TI - Microwave Sintering of Silver Nanoink for Radio Frequency Applications.
AB - Microwave sintering is a promising method for low-temperature processes, as it
provides advantages such as uniform, fast, and volumetric heating. In this study,
we investigated the electrical characteristics of inkjet-printed silver (Ag)
circuits sintered by microwaves. The microstructural evolutions of inkjet-printed
Ag circuits sintered at various temperatures for different durations were
observed with a field emission scanning electron microscope. The electrical
properties of the inkjet-printed Ag circuits were analysed by electrical
resistivity measurements and radio frequency properties including scattering
parameters in the frequency range of 20 MHz to 20 GHz. The experimental results
show that the signal losses of the Ag circuits sintered by microwave heating were
lower than those sintered by conventional heating as microwave heating led to
granular films which were nearly fully sintered without pores on the surfaces.
When the inkjet-printed Ag circuits were sintered by microwaves at 300 degrees C
for 4 min, their electrical resistivity was 5.1 uOmega cm, which is 3.2 times
larger than that of bulk Ag. Furthermore, microwave sintering at 150 degrees C
for 4 min achieved much lower signal losses (1.1 dB at 20 GHz) than conventional
sintering under the same conditions.
PMID- 26413663
TI - Effects of Mass Flow Rate on the Thermal-Flow Characteristics of Microwave CO2
Plasma.
AB - In this study, the thermal-flow characteristics of atmospheric pressure microwave
CO2 plasma were numerically investigated by simulation. The electric and gas flow
fields in the reaction chamber with a microwave axial injection torch operated at
2.45 GHz were simulated. The microwave launcher had the standard rectangular
waveguide WR340 geometry. The simulation was performed by using the COMSOL
Multiphysics plasma model with various mass flow rates of CO2. The electric
fields, temperature profiles and the density of electrons were graphically
depicted for different CO2 inlet mass flow rates.
PMID- 26413664
TI - RF Magnetron Sputtering Grown Cu2O Film Structural, Morphological, and Electrical
Property Dependencies on Substrate Type.
AB - We investigated the structural, morphological, and electrical properties of
cuprous oxide (Cu2O) film dependency on substrate type. Thin films grown using RF
magnetron sputtering were characterized by scanning electron microscopy, X-ray
diffraction (XRD), and Hall effect measurements. Cu2O thin films were deposited
onto sapphire (0001), Si (100), and MgO (110) substrates, and showed Cu2O single
phase only, which was confirmed by XRD measurement. Relatively larger compressive
strain existed in Cu2O film grown on sapphire and Si, while a smaller tensile
strain appeared in Cu2O film grown on MgO. Cu2O thin film crystallite sizes
showed a linear dependence on strain. Moreover, film carrier concentration and
mobility increased with increasing strain, while resistivity decreased with
decreasing strain. Cu2O film strain due to induced strain opens the possibility
of controlling structural and electrical properties in device applications.
PMID- 26413665
TI - Electrospun ZnO Nanofibers as a Photoelectrode in Dye-Sensitized Solar Cells.
AB - A nanoparticle-based DSSC shows limited efficiency levels due to its disordered
geometrical structure and interfacial interference during electron transport,
whereas the use of nanofibers in a DSSC can increase the electron mobility at the
interfacial area of the materials due to the reduced recombination of electrons
before reaching the collecting electrode. In this study, we describe the
fabrication and characteristics of a ZnO nanofiber electrode for DSSC. From the
results of a thermogravimetric analysis, a stepped heat treatment was developed
for the calcinations of the ZnO electrodes. The ZnO electrode morphology and
crystalline structure were confirmed by scanning electron microscopy and the X
ray diffraction patterns, respectively. The DSSC with the ZnO nanofiber
photoelectrode (wire shaped) created by electrospinning showed an enhanced short
circuit current density (37% enhancement) compared to that of a ZnO sphere
particle-shaped photoelectrode under irradiation of AM 1.5 simulated sunlight
(100 mW/cm2). Moreover, we have investigated the origin of the improved
performance through electrochemical impedance spectroscopic (EIS) and open
circuit voltage-decay (OCVD) measurements.
PMID- 26413666
TI - Effect of Bulky and Hydroxyl Groups on Gas Separation Performance of Polyimide
Membranes.
AB - A series of polyimides were synthesized by a polycondensation reaction using
various aromatic dianhydrides and diamines containing bulky cardo and hydroxyl
groups. The imidization and chemical structure of the polyimides were confirmed
by NMR and FT-IR. The thermal and gas properties of the polyimides were measured
by time-lag, XRD, TGA, and DSC studies. The polyimides showed excellent
solubility in common organic solvents and high thermal stability. The CO2
selectivity of HPI membrane was higher than traditional polyimides. In
particular, the incorporation of hydroxyl groups improved the CO2 permeability of
the polyimide due to increased carbon dioxide solubility. The HPI was thermally
converted to polybenzoxazole (PBO) at 450 degrees C.
PMID- 26413667
TI - Magnetocrystalline Anisotropy of d0-Magnetic Material NaN(001) Thin Films: A
Density Functional Study.
AB - A bulk d0 NaN of rocksalt or zinc-blende structure was predicted to be a
ferromagnetic half metal and furthermore the half-metallicity would be retained
in thin films. Such half metallicity of d0 ferromagnetic NaN is attractive for
possible application in a spintronics device, such as a spin transfer torque
magnetic random access memory. In this study, we carried out first-principles
calculations on magnetocrystalline anisotropy rocksalt structured NaN thin films
with different thicknesses, using Vienna Ab-initio Simulation Package code. It
was found that the NaN(001) thin films have perpendicular magnetization with
quite low magnetocrystalline anisotropy energies of order of 10 ueV, but capping
of a 5d-transition metal Ta monolayer over the NaN(001) thin films enhances the
perpendicular magnetocrystalline anisotropy energies significantly, more than 10
times. Furthermore, the 1 (Ta)/NaN(001) systems retain their half-metallicity
except the NaN layer just below Ta.
PMID- 26413668
TI - (Na, K)NbO3-Based Ceramics for Self-Powered Energy Harvesting Applications.
AB - Self-powered energy harvesting technologies have been intensively investigated by
employ- ing Pb-free piezoelectric materials. One such Pb-free piezoelectric
material, the ceramic 0.97(Na0.5K0.5)NbO3-0.03(Bi0.5Na0.5)TiO3, was prepared by
employing the conventional mixed oxide method. 0.97(Na0.5K0.5)NbO3
0.03(Bi0.5Na0.5)TiO3 ceramics were prepared and the effect of sintering
temperature on the microstructure, piezoelectric and ferroelectric properties
were system- atically investigated for energy harvesting applications. The
crystal structure of 0.97(Na0.5K0.5)NbO3- 0.03(Bi0.5Na0.5) TiO3 Pb-free
piezoelectric ceramics, sintered at temperatures between 1080 degrees C and 1160
degrees C, was examined by X-ray diffraction analysis. The dielectric properties
of 0.97(Na0.5K0.5)NbO3-0.03(Bi0.5Na0.5)TiO3 ceramics were measured from 1 kHz to
1 MHz for the various sintering temperatures. We expect that optimization of
sintering parameters can improve the piezoelectric and ferroelectric properties
of 0.97 (Na0.5K0.5)NbO3-0.03(Bi0.5Na0.5)TiO3 ceramics for energy harvesting.
PMID- 26413669
TI - Synthesis of Highly Monodispersed CdS/SiO2 Core-Shell Nanoparticles and Their
Photocatalytic Activities.
AB - Monodispersed CdS/SiO2 core-shell composite nanoparticles with effective
photocatalytic activity were successfully synthesized. The structure and
morphologies of composite nanoparticles were characterized by XRD, FTIR, TEM, and
high-resolution transmission electron microscopy (HRTEM). Results showed that the
CdS/SiO2 composite nanoparticles exhibited obvious core-shell structure, and that
the thickness of the SiO2 shell could be reduced by either increasing the
water/alcohol volume ratio or decreasing TEOS amount. The photocatalytic activity
of the prepared composite nanoparticles was determined by degradation of
methylene blue (MB) in aqueous solution. CdS/SiO2 showed a lower photocatalytic
activity compared with CdS nanoparticles. However, the residual concentration of
Cd2+ in aqueous solution after MB complete degradation was reduced by half.
PMID- 26413670
TI - A Facile Approach to Monodisperse Au Nanoparticles on Fe3O4 Nanostructures with
Surface Plasmon Resonance Amplification.
AB - Composite magnetic nanoparticles, Fe3O4@Au, were synthesized in an aqueous phase
via reducing gold chloride acid (HAuCl4) in-situ on (3-aminopropyl)
triethoxysilane layer around Fe3O4 nanostructures. Connection between gold and
Fe3O4 was confirmed by the magnetic separa- tion technique and X-ray diffraction
(XRD). Transmission electron microscopy (TEM) observation revealed that the gold
nanoparticles were dispersed on the surface of magnetic Fe3O4 nanoparticles.
Significantly, aqueous dispersion of such composite nanoparticles exhibited
surface plasmon of Au nanoparticles. The composite magnetic nanoparticles were
then modified with 3-mercaptopropionic via an Au-S bond. These ligand-modified
nanoparticles were facilely conjugated to anti-penicillin antibody. The resulting
Fe3O4@Au-antibody conjugates were successfully used as a powerful sandwich
element and an excellent amplification reagent for surface plasmon resonance
based sandwich immunoassay. By the amplification effect of Fe3O4 @ Au-antibody
conjugates, there was a nearly 30-fold increase in signal and penicillin in
aqueous solution was detected at a lowest detection limit of 5 ng/ml. The
biological properties of the Fe3O4@Au-antibody conjugates were investigated by
Western Blotting. To our knowledge, this is the first report on the in-situ
synthesis of monodisperse Au nanoparticles on Fe3O4 magnetic nanostructures in an
aqueous solution with surface plasmon resonance amplification.
PMID- 26413671
TI - Elemental and Microscopic Analysis of Naturally Occurring C-O-Si Hetero-Fullerene
Like Structures.
AB - Carbon exhibits an ability to form a wide range of structures in nature. Under
favorable conditions, carbon condenses to form hollow, spheroid fullerenes in an
inert atmosphere. Using high resolution FESEM, we have concealed the existence of
giant hetero-fullerene like structures in the natural form. Clear, distinct
features of connected hexagons and pentagons were observed. Energy dispersive X
ray analysis depth-profile of natural fullerene structures indicates that Russian
doll-like configurations composed of C, 0, and Si rings exist in nature. The
analysis is based on an outstanding molecular feature found in the size fraction
of aerosols having diameters 150 nm to 1.0 um. The fullerene like structures,
which are ~ 150 nm in diameter, are observed in large numbers. To the best of our
knowledge, this is the first direct detailed observation of natural fullerene
like structures. This article reports inadvertent observation of naturally
occurring hetero-fullerene-like structures in the Arctic.
PMID- 26413672
TI - Large-Scale and Selective Synthesis of Carbon Nanofiber Bundles, Curved Carbon
Nanofibers and Helical Carbon Nanofibers.
AB - Through the pyrolysis of acetylene at 250 degrees C, large quantities of carbon
nanofiber bundles (CNFBs), curved carbon nanofibers (CCNFs) and helical carbon
nanofibers (HCNFs) can be synthesized selectively by controlling the Fe:Cu molar
ratio of Fe-Cu nanoparticles. In this study, the systematic experimental results
indicated that the Cu content in the Fe-Cu nanoparticles and pyrolysis
temperature had great impact on the yield and structure of the final samples.
Moreover, the transmission electron microscopic observation indicated that the
catalyst nanoparticles were enwrapped tightly by graphite layers, and the
obtained HCNFs show good magnetic property. Compared to the methods reported in
the literature, the approach described herein has the advantages of being simple,
low-cost, and environment-friendly. It is suitable for the controllable and mass
production of CNFBs, CCNFs and HCNFs.
PMID- 26413673
TI - Hollow Capsules Fabricated by Template Polymerization of N-Vinylcaprolactam.
AB - We report the facile fabrication of polymer capsules based on the template
polymerization of N-vinylcaprolactam (VCL) at the surface of silica particles.
The modification of silica surfaces with methacrylate groups favors the
polymerization of VCL leading to the formation of a homogenous PVCL layer. PVCL
capsules approximately 200 nm in diameter were obtained after removal of the
silica template. In contrast to most of other polymer capsules, the hollow
morphology was maintained even in the dried state. The PVCL capsules, which
possess smart properties based on thermal stimuli, should have wide potential
applications in biological therapy.
PMID- 26413674
TI - Production of Self-Assembled Fullerene (C60) Nanocrystals at Liquid-Liquid
Interface.
AB - Here we present self-assembled nanostructure of functional molecule fullerene
(C60) at liquid-liquid interface. The nanostructured nanocrystals were grown at
liquid-liquid interface of isopropyl alcohol (IPA) and C60 solution in
butylbenzene under ambient condition of temperature and pressure, and
characterized by Raman scattering, power X-ray diffraction (XRD), scanning
electron microscopy (SEM) and transmission electron microscopy (TEM). The crystal
formation mechanism is driven by supersaturation related to the low solubility of
C60 in IPA. A slow diffusion of IPA towards the C60 solution causes unsaturation
of C60 at the liquid-liquid interface and consequently small clusters of C60 is
formed at the interface, which acts as the nucleation site. Further diffusion of
IPA supplies the C60 molecules from bulk to the interface promoting the crystal
growth. Based on SEM and TEM observation, the average size of the individual
hexagonal bipyramid nanocrystal is found to be ca. 1.4 um and the average size of
their assembly is found to be approximately 2 um. XRD measurements have shown
that these materials are crystalline with mixed face-centered cubic (cell
dimension: a = 1.352 nm, and V = 2.475 nm3) and hexagonal (cell dimension: a =
1.452 nm, c = 1.207 nm, c/a = 0.831, and V = 2.475 nm3) structures. Raman
scattering measurements showed two Ag and six Hg vibration bands, which are
similar to those obtained in the pristine C60.
PMID- 26413675
TI - Characteristics of Carrier Collection of Nanopillar-Patterned Silicon Solar
Cells.
AB - Nanopillar-patterned Si solar cells were investigated. Ag nanoparticles were
coated on a polished Si substrate as an etching mask. Reactive ion etching caused
Si nanopillars to replicate in a reverse fashion on the Ag nanoparticles over a
large area. The nanopillar structures efficiently reduced the light reflection on
the surface and effectively drove the incident light into a Si absorber. This
induced a significant enhancement of the photogenerated-current with an improved
solar cell efficiency of 16.07%. The Si nanopillar-patterned solar cells showed
improved carrier collection for long wavelengths; however, the surface-defect
induced recombination degraded the quantum efficiency at short wavelengths. We
suggest that the reduction of recombination loss should be considered for
efficient nanostructure solar cells.
PMID- 26413676
TI - Optimization of Semitransparent Anode Electrode for Flexible Green and Red
Phosphorescent Organic Light-Emitting Diodes.
AB - In this paper, we demonstrated thin film semitransparent anode electrode using
Ni/Ag/Ni (3/6/3 nm) on green and red phosphorescent OLEDs, which have basically
high efficiency and good optical characteristics. Moreover, we applied this
semitransparent anode on flexible green and red phosphorescent OLEDs, which were
then optimized for possible applications on flexible substrates. First, we
studied optimization using various conditions of Ni/Ag/Ni electrodes via
transmittance and sheet resistance. We then fabricated the devices on a glass
substrate with ITO or Ni/Ag/Ni electrodes as well as on a flexible substrate with
a Ni/Ag/Ni electrode for green and red phosphorescent OLEDs. Consequently, we
could be proposed that the potential of our semitransparent anode electrode is
demonstrated. Green phosphorescent OLEDs characteristics using ITO or Ni/Ag/Ni
anode electrodes were coincided and those of the red phosphorescent OLEDs were
improved by semitransparent electrodes at 10,000 cd/m2 criterion. Therefore, this
research suggests for additional studies to be conducted on flexible and high
performance phosphorescent OLED displays and light applications for ITO-free
processes.
PMID- 26413677
TI - YBa2Cu3O6+xSemiconductors Fabricated Using the Aerosol Deposition Method for IR
Sensors.
AB - In this study, YBa2Cu306+x (YBCO) thick films were investigated for their
application in uncooled microbolometers. YBCO powders were prepared using the
conventional mixed oxide method and were deposited on an SiO2/Si substrate using
the aerosol deposition method (ADM) at room temperature. As a result of
thermogravimetry and differential thermal analysis (TG-DTA) of YBCO powder, an
endothermic peak was observed at approximately 820 degrees C. The powder was
calcined at 880 degrees C. The deposited film were annealed at 600-750 degrees
C (O2:Ar = 1:1, pO2) and their structural and electrical properties were
investigated at varying annealing temperatures. From X-ray diffraction (XRD)
results, all films displayed the typical XRD patterns of the tetragonal phase and
the second phase was observed. The thickness of all the YBCO thick films was
approximately 15.7 um. As a result of the temperature coefficient of resistance
(TCR = 1/R * dR/dT), the YBCO thick films annealed at 700 degrees C showed the
maximum value of -3.1%/ degrees C and all YBCO thick films showed typical NTCR
(negative temperature coefficient of resistance) properties, displaying decreased
electrical resistance with an increase in temperature.
PMID- 26413678
TI - Laser Direct Ablation of Indium Tin Oxide Films on Both Sides of Various
Substrates.
AB - We demonstrate ablation of indium tin oxide (ITO) films onto both glass and
polyethylene terephthalate (PET) substrates, using a Q-switched diode-pumped
neodymium-doped yttrium vanadate laser (Nd:YVO4, lambda = 1064 nm) incident on
both the front and back sides of the substrate. From scanning electron microscope
(SEM) images and depth profile data, ITO patterns that were laser-ablated onto
glass from the back side showed a larger abrupt change in the ablated line width
than those ablated from the front. However, there were only slight differences in
ablated line widths due to the direction of the incident laser beam. We provide a
possible explanation in terms of several factors: dispersion of laser beam energy
through the substrate, overlapping of each laser beam spot due to scanning speed,
and the thickness of glass and PET substrates.
PMID- 26413679
TI - Electrochemical Performances of Li2MnSiO4 Cathodes Synthesized by Mechanical
Alloying Process.
AB - We report the fabrication and electrochemical properties of Li2MnSiO4 powders
produced by various solid-state reactions, such as ball-, attrition-, and bead
milling. Li2MnSiO4 powders prepared by bead-milling had the smallest particle
sizes (~100 nm) and the largest amount of surface carbon (~20 wt%), which were
produced by adding sucrose during milling process. The surface carbon layer can
improve electronic/ionic conductivity of Li2MnSiO4 as cathode material for
lithium ion battery. As expected, the bead-milled Li2MnSiO4 powder electrode
showed the best electrochemical performance of the electrode materials obtained
by the various solid-state reactions. This is attributed to the small particle
size and facile electronic transport through the conductive carbon layer on each
Li2MnSiO4 particle.
PMID- 26413680
TI - Electroless Cu Plating on Anodized Al Substrate for High Power LED.
AB - Area-selective copper deposition on screen printed Ag pattern/anodized Al/Al
substrate was attempted using a neutral electroless plating processes for printed
circuit boards (PCBs), according to a range of variation of pH 6.5-pH 8 at 70
degrees C. The utilized basic electroless solution consisted of copper(II)
sulfate pentahydrate, sodium phosphinate monohydrate, sodium citrate tribasic
dihydrate, ammonium chloride, and nickel(II) sulfate hexahydrate. The pH of the
copper plating solutions was adjusted from pH 6.5 to pH 8 using NH4OH. Using
electroless plating in pH 6.5 and pH 7 baths, surface damage to the anodized Al
layer hardly occurred; the structure of the plated Cu-rich films was a typical
fcc-Cu, but a small Ni component was co-deposited. In electroless plating at pH
8, the surface of the anodized Al layer was damaged and the Cu film was composed
of a lot of Ni and P which were co-deposited with Cu. Finally, in a pH 7 bath, we
can make a selectively electroless plated Cu film on a PCB without any
lithography and without surface damage to the anodized Al layer.
PMID- 26413681
TI - Nanomechanical Analysis of a UV Treated Ag Thin Film Based on a Three-Step
Oxidation Model.
AB - Nanoindentation was used as the main method to measure the change in
nanomechanical properties on the surface of an Ag thin film due to UV treatment.
The 4-point probe method, X-ray diffraction (XRD), and atomic force microscopy
(AFM) were used to measure the electrical, crystallographic, and morphological
properties, respectively. During a UV treatment time of between 1 and 3 minutes,
the sheet resistance increased dramatically to 0.55 Omega/sq. (the sheet
resistance was 0.16 Omega/sq. prior to UV treatment) and these results were
supported by a proportional decreased in XRD intensity. Thereafter, the sheet
resistance decreased and the XRD intensity increased in response to increases in
UV treatment time. These results were related to a change in crystal structure
from Ag to AgOx, which could also have caused the change in sheet resistance.
Based on these results, we propose a 3-step oxidation model of an Ag thin film
according to UV treatment time. This proposal has been proven by nanoindentation
testing.
PMID- 26413682
TI - Effects of a Pretreatment on Al-Doped ZnO Thin Films Grown by Atomic Layer
Deposition.
AB - In this study, we investigated the electrical, structural, and optical properties
of Al-doped ZnO (AZO) thin films approximately 50 nm thick grown by atomic layer
deposition (ALD) on glass substrates at 200 degrees C. An H2O pretreatment was
conducted for all AZO samples. The electrical properties of the AZO thin film
were improved after the pretreatment process. The Al doping concentrations were
controlled by inserting an Al2O3 cycle after every "n" ZnO cycles while varying n
from 99 to 16. As the doping concentration increases, the resistivity decreases
and the optical band gap increases. When the Al2O3 cycle ratio is 5%, the
electrical resistivity showed the lowest value of 4.66 x 10(-3) Omega cm. A
carrier concentration of 1.10 x 10(20) cm(-3), and the optical transmittance
exceeding 90% were obtained in the visible and near-infrared region. The thin
film was strongly textured along the (100) direction in the X-ray diffraction
patterns.
PMID- 26413683
TI - Structural and Electrical Properties of Lithium-Ion Rechargeable Battery Using
the LiFePO4/Carbon Cathode Material.
AB - LiFePO4/C composite powder as cathode material and graphite powder as anode
material for Li-ion batteries were synthesized by using the sol-gel method. An
electrochemical improvement of LiFePO4 materials has been achieved by adding
polyvinyl alcohol as a carbon source into as-prepared materials. The samples were
characterized by elemental analysis (EA), X-ray diffraction (XRD), and field
emission scanning electron microscopy (FE-EM). The chemical composition of
LiFePO4/C powders was in a good agreement with that of the starting solution. The
capacity loss after 500 cycles of LiFePO4/C cell is 11.1% in room temperature.
These superior electrochemical properties show that LiFePO4/C composite materials
are promising candidates as cathode materials.
PMID- 26413684
TI - Synthesis of Ordered Mesoporous Manganese Oxides with Various Oxidation States.
AB - Ordered mesoporous MnO, MnO4, Mn2O3 and MnO2 materials with 3-D pore structure
were suc- cessfully synthesized via a nano-replication method by using ordered
mesoporous silica, KIT-6 (Cubic Ia3d space group mesostructure) as the template
under specific oxidation and reduction conditions. Notably, ordered mesoporous
MnO with a crystalline wall (rock salt structure) was syn- thesized for the first
time, to the best of our knowledge. The synthesis of the ordered mesoporous MnO
was achieved by reducing the ordered mesoporous Mn3O4 under an H2 atmosphere,
while preserving the ordered mesostructure and crystalline wall throughout the
solid/solid transformation. All of the ordered mesoporous manganese oxides with
different crystal structures and oxidation states demonstrated almost the same
spherical-like morphology with several hundred nanometers of particles. The
synthesized ordered mesoporous manganese oxides had uniform dual mesopores (2-3
nm, and ~20 nm) and crystalline frameworks with large surface areas (86-140 m2/g)
and pore volumes (0.27-0.33 cm3/g).
PMID- 26413685
TI - Multifunctional Nanobiocomposite of Poly[(butylene succinate)-co-adipate] and
Clay.
AB - The processing and characterization of multifunctional nanobiocomposite of
biodegradable poly[(butylene succinate)-co-adipate] (PBSA) and organically
modified synthetic fluorine mica (OSFM) are reported. The nanobiocomposite of
PBSA with OSFM was prepared using melt- blending, and the structure and
morphology of the nanocomposite were characterized using X-ray diffraction and
transmission electron microscopy. The mechanical and material properties
measurements showed the concurrent improvement in temperature dependence storage
modulus, tensile properties, gas barrier, and thermal stability of neat PBSA
after nanocomposite formation. Such improved inherent properties along with the
environmentally-friendly feature are expected to widen the use of PBSA for short
term food-packaging applications.
PMID- 26413686
TI - Chirality of 4,4'-Biphenylene Bridged Polybissilsesquioxane Nanotubes Using the
Dipeptides Derived from Valine.
AB - Four dipeptides with alkyl chains derived from L- and D-valines were synthesized,
the handedness of their self-assemblies were controlled by the valine chirality
at the terminals. The stacking of the carbonyl groups plays an important in the
formation of chiral organic self-assemblies. Chiral 4,4'-biphenylene bridged
polybissilsesquioxane nanotubes were prepared using the self-assemblies of these
dipeptides as the templates. The chirality of the polysilsesquioxane nanotubes
was mainly controlled by the valines at the terminals of the dipeptides, which
was transferred from the valines at the terminals through electrostatic
interaction. The valines near the alkyl chains could also affect the
polysilsesquioxane chirality through hydrogen bonding.
PMID- 26413687
TI - A Novel Sensitive Electrochemical Sensor for Podophyllotoxin Assay Based on the
Molecularly Imprinted Poly-o-Phenylenediamine Film.
AB - An electrochemical sensor for podophyllotoxin (PPT) based on the molecular
imprinting polymer (MIP) membranes was constructed. The sensor was prepared by
electropolymerizing o-phenylenediamine (o-PD) on a glassy carbon electrode (GCE)
in the presence of PPT as template, and then removing the template by immersing
the modified GCE in ethanol. Experimental parameters such as the types of
monomer, scan cycles, concentration of o-PD and extraction condition were
optimized. Under optimal conditions, the sensor exhibits a good selectivity and
high sensitivity. A good linearity was obtained in the range of 4 x 10-8 mol . L(
1) to 3.2 x 10(-5) mol . L(-1) with an estimated detection limit of 4.8 x 10(-9)
mol . L(-1). The sensor was applied to the determination of PPT in podophyllum
hexandrum and human serum samples with satisfactory results.
PMID- 26413688
TI - Palladium Decorated Graphene-Nanoribbon Network for Enhanced Gas Sensing.
AB - The fabrication of large-scale graphene nanoribbon (GNR) network and its
application for gas sensing are reported. A large area, nanoscale GNR network was
produced by a facile approach of silver nanowires (Ag NWs) templated graphene
masking and subsequent 02 plasma etching. GNR network shows significantly
enhanced sensitivity to ammonia gas compared to pristine graphene layer. The gas
detection sensitivity of the nanoscale GNR network is even further improved by
decorating GNR network with palladium (Pd) or platinum (Pt) nanoparticles, which
show a relative resistance response of 65% and 45%, respectively to 50 ppm (parts
per million) of ammonia (NH3) in nitrogen (N2) at room temperature as well as
good reversibility in air.
PMID- 26413689
TI - Novel Gas Sensor Based on ZnO Nanorod Circular Arrays for C2H5OH Gas Detection.
AB - Novel side-heating gas sensor based on ZnO nanorod circular arrays was firstly
fabricated by hydrothermal treatment assisted with a kind of simple dip-coating
technique. The structure and morphologies of ZnO nanorods were characterized by X
ray diffraction (XRD), Scanning Electron Microscope (SEM), respectively. XRD
result indicates that the obtained ZnO nanorods have good crystalline with the
hexagonal wurtzite structure. SEM result indicates that ZnO nanorod arrays are
vertically growth on the surface of ceramic tube of side-heating sensor with
controlled diameter and length, narrow size distribution and high orientation.
The gas sensing properties of ZnO nanorod circular arrays are also evaluated.
Comparative to the sensor based on scattered ZnO nanorods responding to 25 ppm
H2, CO, C6H5CH3 and C2H5OH gas, respectively, the sensing values of high
orientation gas sensor are generally increased by 5%. This novel sensor has good
application promising for the fabrication of cost effective and high performance
gas sensors.
PMID- 26413690
TI - Theoretica Study of Asymmetric Double D-pi-A Organic Sensitizers for Efficient
Dye-Sensitized Solar Cells.
AB - Three novel dye sensitizers that were based on asymmetric double D-pi-A chains
with phenoxazine (POZ) and diphenylamine (DPA) as electron donors and cyanoacetic
acid (CA) and 2-(1,1- dicyanomethylene) rhodanine (RD) as electron acceptors
(DCPR, DRPC, DRPR) were designed, theoretically investigated, and compared with
the reference dye based on asymmetric double D-pi-A chains (DCPC). Using density
functional theory (DFT) and time-dependent density functional theory (TD-DFT)
calculations, we gained insight into the factors responsible for the photovoltaic
properties of the dye sensitizers. Due to the different HOMO levels of each donor
and the different LUMO levels of each acceptor, the absorption spectrum of each
dye showed different shapes. Among the dyes, DRPR showed a broader and more
bathochromically shifted absorption band than the other dies. It also showed a
higher molar extinction coefficient than that of the reference dye (DCPC). This
work suggests optimizing the chain of electron donors and acceptors in dye
sensitizers based on asymmetric double D-pi-A chains would produce good
photovoltaic properties for dye-sensitized solar cells (DSSCs).
PMID- 26413691
TI - Effect of an Ag Insertion Layer on the Optical and Electrical Properties of Ga
Doped Zinc Oxide Films.
AB - GZO/Ag/GZO films were investigated for use as high quality transparent conductive
electrodes. The GZO and Ag films were deposited by RF sputtering and electron
beam evaporation, respectively, at room temperature. The effects of Ag thickness
and post heat treatment on the structural, electrical and optical properties of
these multilayer films were investigated. The insertion of the Ag layer with
optimized thickness between the GZO layers and the optimized annealing
temperature improved the electrical and optical properties of the GZO/Ag/GZO film
due to the very low resistivity and surface plasmon effect of the Ag layer. The
best multilayer film exhibited a low resistivity of 2.2 x 10(-5) Omega . cm and a
transmittance of 88.9%.
PMID- 26413692
TI - Novel Ru(II) Complex with 1H-Benzo[d]lmidazole Derivative for Dye-Sensitized
Solar Cell.
AB - It was reported that ruthenium(II) complex CBTR with 1H-benzo[d]imidazole
derivative for heteroleptic donor system exhibited an enhancement of the solar
cell performance, compared to N3. We took a theoretical approach about the CBTR
dye. Density functional theory (DFT) and time-dependent density functional theory
(TD-DFT) calculations were used to gain insight into the factors responsible for
the photovoltaic properties of the dye sensitizer. The values of the absorption
spectrum of the CBTR dye with the 1 H-benzo[d]imidazole derivative were not
improved compared to those of the N3 dye. The lack of improvement was attributed
to the destabilization of the lowest unoccupied molecular orbital (LUMO) energy
level of the CTBR dye. According to the molecular orbital analysis, the LUMO of
the CBTR dye mainly localized on the dcbpy (dcbpy = 4,4'-dicarboxy-2,2'
bipyridine) moiety. The highest occupied molecular orbitals (HOMOs) of N3 were
localized on the Ru-NCS moiety, and the HOMOs of CBTR were also localized on Ru
NCS. The introduction of the 1H-benzo[d]imidazole derivative to the heteroleptic
donor system did not change the location of the HOMOs. The addition on of the NHC
ligand to the CBTR dye seems to be an essential structural modification to
enhance the efficiency of solar cells.
PMID- 26413693
TI - Effect of Sulfurization Temperature on Solution-Processed Cu2ZnSnS4 Thin Films.
AB - Cu2ZnSnS4 (CZTS) solar cells are attracting significant attention as an
alternative to CIGS (Culn1-xGa(x)S2) solar cells because of the non-toxic and
inexpensive constituent elements of CZTS. Recently, solution-based deposition
methods are being developed because they have advantages such as suitability for
use in large-area deposition, high-throughput manufacturing, and a very short
energy payback time with drastically lower manufacturing costs. In this work, we
fabricated solution-based CZTS thin films and investigated them in order to
observe the effects of sulfurization temperature on CZTS thin films. We confirmed
the grain size, morphology, chemical composition, crystallinity, and electrical
properties of CZTS thin films depending on various sulfurization temperatures.
PMID- 26413694
TI - Crystallization Behavior of Solution-Processed CIGSe Thin Film Semiconductor by
Stepwise Annealing Process.
AB - CuIn(x)Ga1-xSe2 (CIGS) thin films were prepared by a solution-based CuInGa (CIG)
precursor- selenization process. First, we investigated the effect of
selenization temperature on the formation of polycrystalline CIGS and grain
growth. The CIG precursor films were selenized using a two-step process to
investigate the reaction of Se and CIG precursors during the formation of CIGS
thin films. Depending on the temperature in the 1st step of the selenization
process, the CIG precursor forms a different intermediate phase between the
single phase to ternary phase such as Cu, Se, CuSe, InSe, and CuInSe2. In
addition, the intermediate phase exerts a significant influence on the final
phase obtained after the 2nd step of the selenization process, particularly with
regard to characteristics such as polycrystalline structure and grain growth in
the CIGS films. The photoelectron conversion efficiency of devices prepared using
CIGS thin films was approximately 1.59-2.75%.
PMID- 26413695
TI - Surface Morphology and Structural Modification Induced by Femtosecond Pulses in
Hydrogenated Amorphous Silicon Films.
AB - This work investigates the modification, resulting from fs-laser irradiation (150
fs, 775 nm and 1 kHz), on the structure and surface morphology of hydrogenated
amorphous silicon (a-Si:H) thin films. The sample morphology was studied by
performing a statistical analyzes of atomic force microscopy images, using a
specially developed software that identifies and characterizes the domains
(spikes) produced by the laser irradiation. For a fluence of 3.1 MJ/m2, we
observed formation of spikes with smaller average height distribution, centered
at around 15 nm, while for fluencies higher than 3.7 MJ/m2 aggregation of the
produced spikes dominates the sample morphology. On the other hand, Raman
spectroscopy revealed that a higher crystalline fraction (73%) is obtained for
higher fluences (> 3.1 MJ/m2), which is accompanied by a decrease in the size of
the produced crystals. Therefore, such results indicate that there is a trade-off
between the spike distribution, crystallization fraction and size of the
nanocrystals attained by laser irradiation, which has to be taken into account
when using such approach for the development of devices.
PMID- 26413696
TI - An Alternative to Annealing TiO2 Nanotubes for Morphology Preservation:
Atmospheric Pressure Plasma Jet Treatment.
AB - Titanium oxide nanotube layer formed by plasma electrolytic oxidation (PEO) is
known to be excellent in biomaterial applications. However, the annealing process
which is commonly performed on the TiO2 nanotubes cause defects in the
nanotubular structure. The purpose of this work was to apply a non-thermal
atmospheric pressure plasma jet on diameter-controlled TiO2 nanotubes to mimic
the effects of annealing while maintaining the tubular structure for use as
biomaterial. Diameter-controlled nanotube samples fabricated by plasma
electrolytic oxidation were dried and prepared under three different conditions:
untreated, annealed at 450 degrees C for 1 h in air with a heating rate of 10
degrees C/min, and treated with an air-based non-thermal atmospheric pressure
plasma jet for 5 minutes. The contact angle measurement was investigated to
confirm the enhanced hydrophilicity of the TiO2 nanotubes. The chemical
composition of the surface was studied using X-ray photoelectron spectroscopy,
and the morphology of TiO2 nanotubes was examined by field emission scanning
electron microscopy. For the viability of the cell, the attachment of the
osteoblastic cell line MC3T3-E1 was determined using the water-soluble
tetrazolium salt assay. We found that there are no morphological changes in the
TiO2 nanotubular structure after the plasma treatment. Also, we investigated a
change in the chemical composition and enhanced hydrophilicity which result in
improved cell behavior. The results of this study indicated that the non-thermal
atmospheric pressure plasma jet results in osteoblast functionality that is
comparable to annealed samples while maintaining the tubular structure of the
TiO2 nanotubes. Therefore, this study concluded that the use of a non-thermal
atmospheric pressure plasma jet on nanotube surfaces may replace the annealing
process following plasma electrolytic oxidation.
PMID- 26413697
TI - Synthesis of Cerium-Doped Titania Nanoparticles and Nanotubes.
AB - Cerium-doped titania nanoparticles and nanotubes were synthesized via
hydrothermal processes. X-Ray Diffraction revealed that cerium-doped titania
nanoparticles have an anatase crystal structure, while cerium-doped titania
nanotubes have an H2Ti3O7-type structure. Scanning electron microscopy and high
resolution transmission electron microscopy showed that both types of titania are
well crystallized with relatively uniform size distribution. The photocatalytic
degradation of methylthioninium chloride known as methylene blue dye was tested
and both cerium-doped titania nanoparticles and nanotubes. The preliminary
photocatalytic degradation of Methylene Blue data showed significantly improved
visible light photocatalytic activities as compared to commercial titania
powders.
PMID- 26413698
TI - Synthesis of Polypropylene/Organoclay Nanocomposites via In Situ Polymerization
with Improved Thermal and Dynamic-Mechanical Properties.
AB - Preparation of polypropylene/clay nanocomposites via in situ polymerization is
investigated. MgCl2/organophilic clay bi-supported Ziegler-Natta catalysts were
used to prepare these nanocomposites. Three organophilic clays (Cloisite 30B,
Cloisite 15A, and Claytone HY) were used as support and reinforcement agents. The
nanostructure of the composites was characterized by X-ray diffraction. The
results showed that the most active catalyst was that with clay having high inter
layer spacing without functional OH groups. Moreover, the silica layers of the
clays (Cloisite 15A and Claytone HY) in these polypropylene/clay nanocomposites
were exfoliated and well dispersed in the polypropylene matrix. Differential
scanning calorimetric was used to investigate both melting and crystallization
temperatures, as well as the crystallinity of the nanocomposite samples. These
results showed that Cloisite 15A and Claytone HY acted as nucleating agents in
the process of crystallization of polypropylene. Thermogravimetric analysis
showed that Cloisite 15A and Claytone HY promoted an increase in resistance to
thermal degradation. Dynamic-mechanical analysis showed that nanocomposites
presented an increase in the storage modulus. Furthermore, Cloisite 15A and
Claytone HY promoted an increase in glass transition temperature. Small-angle X
ray scattering analysis was used to determine how clay and its concentration
influence the size of the polymer nanocrystals.
PMID- 26413699
TI - Macroparticles Reduction Using Filter Free Cathodic Vacuum Arc Deposition Method
in ZnO Thin Films.
AB - We report a new method to reduce macroparticles in ZnO thin films using filter
free cathodic vacuum arc deposition without using any cooling arrangements
operated at low arc current. The detailed mechanism has been proposed to reduce
macroparticles during thin film deposition. The successful reduction of
macroparticles was confirmed employing FESEM-EDX studies. FESEM images of ZnO
thin films deposited with cathode spot to substrate distance from 10 to 20 cm
revealed that the population of the macroparticles were reduced with the increase
of cathode spot to substrate distances at low arc current. The prepared ZnO films
were characterised and showed good structural and optical properties.
PMID- 26413700
TI - Superhydrophilic and Highly Transparent TiO2 Films Prepared by Dip Coating for
Photocatalytic Degradation of Methylene Blue.
AB - Nanocrystalline TiO2 films were prepared on slide glass by sol-gel and dip
coating methods, and the samples were then annealed at 200 degrees C, 250
degrees C, 300 degrees C, 350 degrees C, 400 degrees C, 450 degrees C and 500
degrees C for 2 h. The samples' crystal structures, morphology, water contact
angle, transmission spectra, and photocatalytic performance with respect to the
degradation of methylene blue (MB) under UV light irradiation were characterized
by X-ray diffraction spectroscopy, scanning electron microscopy, contact angle
measurement, and UV-vis spectrophotometry. The results obtained indicate that all
of the films were highly transparent to the visible spectrum, but with an
increase in the annealing temperature, the optical band-gap and the water contact
angle both reduced. Samples annealed at 450 degrees C and 500 degrees C
exhibited superhydrophilic properties, with the hydrophilicity of the films
remaining stable for at least 6 months without UV light irradiation. Among all
the samples, the one annealed at 450 degrees C was found to have the highest
maximum MB degradation rate of 71.1%.
PMID- 26413701
TI - Chitosan-Polypyrrole Fiber for Strain Sensor.
AB - A chitosan/polypyrrole composited fiber as bio-compatible materials for
artificial muscles is investigated. The chitosan/polypyrrole fiber (CPF) is
fabricated by in-situ chemical polymerization of pyrrole monomer solution using
FeCl3 as an oxidant. The electrical resistivity of the fiber is changed according
to the strain variation applied to the both ends of the specimen. The sensor
built by using the CPF has a higher gauge factor (4) compared to conventional
metal strain gauges (~2) indicating a suitable material for delicate force
control in sensing work.
PMID- 26413702
TI - Control of Size Uniformity of Cu Nanoparticle Array Produced by Plasma-Induced
Dewetting.
AB - The effects of plasma parameters such as plasma density, electron temperature,
and sheath voltage on the uniformity of Cu nanoparticle arrays were investigated.
These parameters were controlled by varying the pressure, RF power, and substrate
bias voltage. A floating harmonic method was used to monitor the plasma
parameters. Uniform nanoparticle arrays were produced when hole generation was
increased by using a high ion.bombardment energy. As oppose to a low energy flux
condition, where small and large nanoparticles coexisted due to a small number of
holes, a larger number of holes was generated and distributed more uniformly
during a high energy flux condition.
PMID- 26413703
TI - CO2 Gas Transport Property of Sulfonated Poly(Arylenen Ether Sulfone) Copolymer
Membrane.
AB - The effect of functional groups such as sulfuric acid group and metal ions on the
CO2 gas transport property of membranes was investigated. Sulfonated poly(arylene
ether sulfone) (SPAES) was prepared by direct copolymerization with a non
sulfonated monomer and sulfonated monomer. The sulfonation degree of SPAES was
controlled from 0 to 50%. Metal ions such as lithium and sodium were substituted
for the protons of the -SO3H group. The thermal properties, microstructure of
polymer chains, and the permeability and selectivity of membranes were evaluated.
The solubility coefficient of CO2 gas increased with an increase in sulfonation
degree. But the diffusivity was largely decreased and the CO2/N2 selectivity of
the membrane substituted for metal ions was increased.
PMID- 26413704
TI - Biomimetic Deposition of Hydroxyapatite by Mixed Acid Treatment of Titanium
Surfaces.
AB - A simple chemical method was established for inducing bioactivity of Ti metal. In
the present study, two kinds of mixed acid solutions were used to treat Ti
specimens to induce Ca-P formation. Following a strong mixed acid activation
process, Ca-P coatings successfully formed on the Ti surfaces in the simulated
body fluid. Strong mixed acid etching was used to increase the roughness of the
metal surface, because the porous and rough surfaces allow better adhesion
between Ca-P coatings and substrate. Nano-scale modification of titanium surfaces
can alter cellular and tissue responses, which may benefit osseointegration and
dental implant therapy. Some specimens were treated with a 5 M NaOH aqueous
solution, and then heat treated at 600 degrees C in order to form an amorphous
sodium titanate layer on their surface. This treated titanium metal is believed
to form a dense and uniform bone-like apatite layer on its surface in a simulated
body fluid (SBF). This study proved that mixed acid treatment is not only
important for surface passivation but is also another bioactive treatment for
titanium surfaces, an alternative to alkali treatment. In addition, mixed acid
treatment uses a lower temperature and shorter time period than alkali treatment.
PMID- 26413705
TI - Monoethanolamine Impregnation of Titanosilicate Zeolite ETS-10.
AB - ETS-10, a mixed octahedral/tetrahedral titanosilicate molecular sieve, has a
unique architecture where its 0.8 nm pores are lined exclusively with silicon
which imparts a high degree of chemical stability, yet the anionic framework can
be modified by cation exchange. In this work, the hydrogen-exchanged form of ETS
10 was impregnated with monoethanolamine and the thermal stability and CO2
adsorption characteristics were analyzed. The surface area of the material was
characterized by N2 physisorption, the thermal stability of the material assessed
through TG-MS experiments, the CO2 capacity was measured via static volumetric
adsorption experiments, and the influence of moisture as a carbamate promoter was
investigated through a series of gravimetric CO2 adsorption/desorption cycling
experiments. Several measurements converge on ~7 wt% monoethanolamine loading
which occupies about half of the available pore volume of the sieve. The results
suggest that the monoethanolamine is so effectively retained by the molecular
sieve that, while the amine is effectively immobilized, under both humid and dry
process streams the monoethanolamine is either chemically or sterically hindered
and is unable to react measurable quantities of CO2.
PMID- 26413706
TI - Sb-Doped SnO2 Nanoparticles Synthesized by Sonochemical-Assisted Precipitation
Process.
AB - Sb-doped SnO2 nanopowders were synthesized by sonochemical-assisted precipitation
process using stannic chloride pentahydrate (SnCl4.5H2O) and antimony chloride
(SbC3) as starting precursors. Effect of sonication and Sb doping concentrations
on physical structures and electrical properties of Sb-doped SnO2 nanoparticles
were investigated by X-ray diffraction, transmission electron microscope, X-ray
photoelectron spectroscopy, Raman spectroscopy and two-point probe method. The
results indicated that the good dispersion with less agglomeration of particles
in SnO2 phase can be obtained by single step sonochemical-assisted process.
Moreover, XRD results indicated that the crystallinity of Sb-doped SnO2
nanopowders deteriorated with increasing Sb content, suggesting that Sb dopant
significantly prevent SnO2 crystallite growth. The XPS spectra of Sb-doped SnO2
obviously confirmed the existence of Sb ion incorporated into SnO2 matrix. These
results revealed that incorporation of Sb ions into SnO2 lattice with specific
concentration has significant influence on formation and crystallization and can
dramatically enhance the conductivity of tin oxide.
PMID- 26413707
TI - Application of 8YSZ Nanopowder Synthesized by the Modified Solvothermal Process
for Anode Supported Solid Oxide Fuel Cells.
AB - Thin electrolyte yttria-stabilized zirconia (8YSZ) films were coated on the
porous solid oxide fuel cell (SOFC) anode substrates for the use at an
intermediate temperature range. Nano-8YSZ powder with a particle size of about 5
nm was synthesized using the modified solvothermal process. The electrolyte
suspension was prepared by dispersion the synthesized 8YSZ nanopowder in ethanol,
with PVB and 1,3-propanediol as a binder and a charging agent respectively. The
8YSZ suspension was subsequently deposited on the pre-sintered NiO-YSZ porous
substrates by the electrophoretic deposition (EPD) technique. In order to obtain
high quality electrolyte films, preparation process was optimized through two
strategic approaches; (i) adjustment of suspension's rheological property and
(ii) compatibility of anode-electrolyte sintering shrinkage. Rheological property
of the suspension was improved with an addition of 1,3-propanediol. The zeta
potential of this suspension was increased and reached the value of +24 mV so the
well-dispersed slurry was finally obtained. The second approach was achieved by
using a proper composite anode powders. Dense and uniform 8YSZ electrolyte films
with a thickness of about 1 thickness successfully be formed on the NiO-YSZ
porous substrates after co-sintering at 1400 degrees C for 2 h.
PMID- 26413708
TI - Behavior of Ultra Fine Particles in Electric Field.
AB - The behavior of ultra fine particles in an electric field was measured in order
to apply it to classification of fine particles. The sample particles used are
spherical polystyrene particles with the average size of 0.03, 0.1, 1.0, 4.3 and
9.6 um. The forces acting the particles in an electric field are considered to be
electrical force, friction force and some other forces like the asymmetric effect
and electrophoretic retardation effect which appear in ionic behavior. We found
that the moving velocity of particles depends on the particle size. When the
particle size is less than 1 um, the velocity increases with increasing the
particle size. On the other hand, the velocity deceases with an increase in the
particle size, when the particle size is larger than 1 um. We can apply the
behavior to classification of fine particles. The phenomena could be explained by
various forces acting the fine particles in the electric field.
PMID- 26413709
TI - Rapid Solidification and Magnetic Properties of (Fe,Co)-(Fe,Co)17Gd2 Pseudo
Binary Eutectic Alloys.
AB - The (Fe,Co)-(Fe,Co)17Gd2 pseudo-binary eutectic system has been determined by
investigating phase compositions on the analysis of DSC, EDS and XRD. The rapid
solidification of Gd7.3Fe30.56Co62.14, Gd9Fe30Co61 and Gd9.63Fe29.79Co60.58
ternary alloys is realized by single roller techniques. With a rising cooling
rate, the equiaxed zone near the roller surface expands inwards. For
Gd7.3Fe30.56Co62.14 hypoeutectic alloy ribbons, the feathery irregular eutectic
zone shrinks and the grains (Fe,Co) near the free surface are refined. (Fe,Co)
equiaxed dendrites plus the radial, irregular eutectic ultimately fill in the
ribbon at the maximum cooling rate. For Gd9Fe30Co61 near-eutectic alloy ribbons,
the growth direction of irregular eutectics near the free surface becomes more
and more perpendicular to the surface, and finally the whole ribbons are occupied
by the fine, irregular eutectic. The dendritic spacing of the (Fe,Co)17Gd2 phase
which grows from the roller surface to the free surface in Gd9.63Fe29.79Co60.58
alloy ribbons becomes smaller. The grain size of the (Fe,Co)17Gd2 dendrite and
the fraction of (Fe,Co) soft phase in alloy ribbons, which determine coercivity
in the pseudo-binary eutectic system, vary with the increase of the cooling rate.
Of the three alloys, the Gd9Fe30Co61 alloy has the best hard magnetic properties
at Vr = 20 m/s; the maximum coercivity Hc is 431.34 Oe.
PMID- 26413710
TI - Effects of Li4Ti5O12 Anode Electrode Thickness on the Cell Balancing of Hybrid
Super Capacitor.
AB - The hybrid super capacitor was prepared by controlling the anode electrode
thickness to optimize cell balancing. With an increasing anode electrode
thickness, the internal resistance increased, while the capacitance was not
changed remarkably. The potential of the cathode increased and that of the anode
was decreased with the working voltage. However, the potential variation of the
cathode was larger than that of the anode due to the difference in the reaction
mechanism of the cathode and anode. The discharge capacity retention as a
function of the current rates increased and the cycle performance was improved
with an increasing anode electrode thickness. The effects of the anode electrode
thickness on the electrode potential are also discussed.
PMID- 26413711
TI - Calvin Ross Scott, 1922-2015.
PMID- 26413712
TI - Working toward Best Practice: Microbubble Filtration and Patient Safety During
Extracorporeal Circulation.
PMID- 26413713
TI - Response to Letter "Working toward Best Practice: Microbubble Filtration and
Patient Safety during Extracorporeal Circulation" by Daniel P. Herbst.
PMID- 26413714
TI - Prediction of telephone calls load using Echo State Network with exogenous
variables.
AB - We approach the problem of forecasting the load of incoming calls in a cell of a
mobile network using Echo State Networks. With respect to previous approaches to
the problem, we consider the inclusion of additional telephone records regarding
the activity registered in the cell as exogenous variables, by investigating
their usefulness in the forecasting task. Additionally, we analyze different
methodologies for training the readout of the network, including two novel
variants, namely nu-SVR and an elastic net penalty. Finally, we employ a genetic
algorithm for both the tasks of tuning the parameters of the system and for
selecting the optimal subset of most informative additional time-series to be
considered as external inputs in the forecasting problem. We compare the
performances with standard prediction models and we evaluate the results
according to the specific properties of the considered time-series.
PMID- 26413715
TI - Laser-Supported Dual Energy X-Ray Absorptiometry (DXL) Compared to Conventional
Absorptiometry (DXA) and to FRAX as Tools for Fracture Risk Assessments.
AB - Dual X-ray and Laser (DXL) adds a measure of the external thickness of the heel,
measured by laser, to a conventional measurement of bone mineral density (BMD) of
the calcaneus, using Dual energy X-ray Absorptiometry (DXA). The addition of heel
thickness aims at a better separation of fatty tissue from bone than the standard
method of DXA, which may mistake fatty tissue for bone and vice versa. The
primary aim of this study was to evaluate whether DXL of the calcaneus can be
used to assess the 10-year risk of fractures. Secondary aims were to compare the
predictive ability of DXL with the two most established methods, Dual energy X
ray Absorptiometry (DXA) of the hip and spine and the WHO fracture risk
assessment tool, FRAX. In 1999 a cohort of 388 elderly Swedish women (mean age
73.2 years) was examined with all three methods. Prospective fracture data was
collected in 2010 from health care registers. One SD decrease in BMD of the heel
resulted in an age-adjusted Hazard Ratio (HR) of 1.47 for a hip fracture (95% CI
1.09-1.98). Harrell's C is the Cox regression counterpart of the Area Under Curve
(AUC) of the Receiver Operating Characteristic (ROC) as a measure of predictive
accuracy. Harrell's C for BMD of the calcaneus was 0.65 for prediction of hip
fractures. These results were not significantly different from those for BMD of
the femoral neck or for FRAX. The HR for a hip fracture, for one SD decrease in
BMD at the femoral neck, was 1.72 (95% CI 1.21-2.44. Harrell's C was 0.67 for BMD
at the femoral neck and 0.59 for FRAX. We conclude that DXL of the calcaneus
could be a useful tool for fracture risk assessments.
PMID- 26413717
TI - Diagnostic Utility of Unbiased Circulating Tumour Cell Capture through Negative
Depletion of Peripheral Blood Cells.
AB - OBJECTIVES: Cytological analysis of peripheral blood circulating tumour cells
(CTCs) is a potential method of confirmatory clinical diagnosis of cancer.
However, cell capture methods tend to be biased and captured cells are not
usually portable resulting in difficulties in pathology reporting. We evaluated
unbiased cell capture through depletion of unwanted normal cells and conventional
clinical analyses of captured cells. METHODS: Blood was sampled from 29 patients
who underwent surgery for suspected lung cancer. It was processed using two
different depletion cocktails. After depletion of unwanted cells, the resultant
cell pellet was processed onto glass slides or embedded into FFPE blocks and
stained using standard haematoxylin and eosin staining followed by cytopathologic
assessment. Two pathologists performed the assessment independently. RESULTS: The
CTCs were identified in 38-45% of cases using CD45 depletion cocktail with the
cell pellet processed on a glass slide, while other combinations of methods
produced poorer results. Overall, there was a good concordance between the
pathologists (up to 91.3%). The sensitivity of cancer diagnosis was 42% (95% CI
23-63%), while the specificity was 100% (95% CI 29-100%). CONCLUSION: Negative
depletion can be used to isolate CTCs in standard clinical settings; however,
more effective ways of detection are required to increase the sensitivity of the
diagnosis.
PMID- 26413716
TI - A GWAS Study on Liver Function Test Using eMERGE Network Participants.
AB - INTRODUCTION: Liver enzyme levels and total serum bilirubin are under genetic
control and in recent years genome-wide population-based association studies have
identified different susceptibility loci for these traits. We conducted a genome
wide association study in European ancestry participants from the Electronic
Medical Records and Genomics (eMERGE) Network dataset of patient medical records
with available genotyping data in order to identify genetic contributors to
variability in serum bilirubin levels and other liver function tests and to
compare the effects between adult and pediatric populations. METHODS: The process
of whole genome imputation of eMERGE samples with standard quality control
measures have been described previously. After removing missing data and outliers
based on principal components (PC) analyses, 3294 samples from European ancestry
were used for the GWAS study. The association between each single nucleotide
polymorphism (SNP) and total serum bilirubin and other liver function tests was
tested using linear regression, adjusting for age, gender, site, platform and
ancestry principal components (PC). RESULTS: Consistent with previous results, a
strong association signal has been detected for UGT1A gene cluster (best SNP
rs887829, beta = 0.15, p = 1.30x10-118) for total serum bilirubin level. Indeed,
in this region more than 176 SNPs (or indels) had p<10-8 spanning 150Kb on the
long arm of chromosome 2q37.1. In addition, we found a similar level of magnitude
in a pediatric group (p = 8.26x10-47, beta = 0.17). Further imputation using
sequencing data as a reference panel revealed association of other markers
including known TA7 repeat indels (rs8175347) (p = 9.78x10-117) and rs111741722
(p = 5.41x10-119) which were in proxy (r2 = 0.99) with rs887829. Among rare
variants, two Asian subjects homozygous for coding SNP rs4148323 (G71R) were
identified. Additional known effects for total serum bilirubin were also
confirmed including organic anion transporters SLCO1B1-SLCO1B3, TDRP and ZMYND8
at FDR<0.05 with no gene-gene interaction effects. Phenome-wide association
studies (PheWAS) suggest a protective effect of TA7 repeat against
cerebrovascular disease in an adult cohort (OR = 0.75, p = 0.0008). Among other
liver function tests, we also confirmed the previous effect of the ABO blood
group locus for variation in serum alkaline phosphatase (rs579459, p = 9.44x10
15). CONCLUSIONS: Taken together, our data present interesting findings with
strong confirmation of previous effects by simply using the eMERGE electronic
health record phenotyping. In addition, our findings indicate that similar to the
adult population, the UGT1A1 is the main locus responsible for normal variation
of serum bilirubin in pediatric populations.
PMID- 26413718
TI - The Effect of Post-Exercise Cryotherapy on Recovery Characteristics: A Systematic
Review and Meta-Analysis.
AB - The aim of this review and meta-analysis was to critically determine the possible
effects of different cooling applications, compared to non-cooling, passive post
exercise strategies, on recovery characteristics after various, exhaustive
exercise protocols up to 96 hours (hrs). A total of n = 36 articles were
processed in this study. To establish the research question, the PICO-model,
according to the PRISMA guidelines was used. The Cochrane's risk of bias tool,
which was used for the quality assessment, demonstrated a high risk of
performance bias and detection bias. Meta-analyses of subjective characteristics,
such as delayed-onset muscle soreness (DOMS) and ratings of perceived exertion
(RPE) and objective characteristics like blood plasma markers and blood plasma
cytokines, were performed. Pooled data from 27 articles revealed, that cooling
and especially cold water immersions affected the symptoms of DOMS significantly,
compared to the control conditions after 24 hrs recovery, with a standardized
mean difference (Hedges' g) of -0.75 with a 95% confidence interval (CI) of -1.20
to -0.30. This effect remained significant after 48 hrs (Hedges' g: -0.73, 95%
CI: -1.20 to -0.26) and 96 hrs (Hedges' g: -0.71, 95% CI: -1.10 to -0.33). A
significant difference in lowering the symptoms of RPE could only be observed
after 24 hrs of recovery, favouring cooling compared to the control conditions
(Hedges' g: -0.95, 95% CI: -1.89 to -0.00). There was no evidence, that cooling
affects any objective recovery variable in a significant way during a 96 hrs
recovery period.
PMID- 26413720
TI - Correction: Decrypting Financial Markets through E-Joint Attention Efforts: On
Line Adaptive Networks of Investors in Periods of Market Uncertainty.
PMID- 26413719
TI - Marital Status, Lifestyle and Dementia: A Nationwide Survey in Taiwan.
AB - BACKGROUND: Evidence of an association between lifestyle and marital status and
risk of dementia is limited in Asia. METHODS: In this nationwide population-based
cross-sectional survey, participants were selected by computerized random
sampling from all 19 counties in Taiwan. A total of 10432 residents were assessed
by a door-to-door in-person survey, among whom 7035 were normal and 929 were
diagnosed with dementia using the criteria recommended by National Institute on
Aging-Alzheimer's Association. Premorbid lifestyle habits and demographic data
including marital status were compared between normal subjects and participants
with dementia. RESULTS: After adjustment for age, gender, education, body mass
index, smoking, drinking, marital status, sleep habits, exercise, social
engagement and co-morbidities including hypertension, diabetes and
cerebrovascular diseases, an increased risk for dementia was found in people with
widow or widower status (OR 1.42, 95% CI 1.15-1.77) and people who used to take a
nap in the afternoon (OR 1.33, 95% CI 1.02-1.72). Decreased risk was found in
people with the habit of regular exercise (OR 0.12, 95% CI 0.09-0.16), adequate
night sleep (OR 0.55, 95% CI 0.39-0.76) and regular social engagement (OR 0.53,
95% CI 0.36-0.77). CONCLUSIONS: Our results provide preliminary evidence of
possible risk-reduction effects for dementia, including regular exercise even in
modest amounts, social engagement and adequate night sleep, whereas people with
the widow/widower status or who used to take an afternoon nap might have
increased risk of dementia.
PMID- 26413721
TI - Correction to Aydin, Frohmader, and Akil (2015).
PMID- 26413722
TI - Binaural cues provide for a release from informational masking.
AB - Informational masking (IM) describes the insensitivity of detecting a change in
sound features in a complex acoustical environment when such a change could
easily be detected in the absence of distracting sounds. IM occurs because of the
similarity between deviant sound and distracting sounds (so-called similarity
based IM) and/or stimulus uncertainty stemming from trial-to-trial variability
(so-called uncertainty-based IM). IM can be abolished if similarity-based or
uncertainty-based IM are minimized. Here, we modulated similarity-based IM using
binaural cues. Standard/deviant tones and distracting tones were presented
sequentially, and level-increment thresholds were measured. Deviant tones
differed from standard tones by a higher sound level. Distracting tones covered a
wide range of levels. Standard/deviant tones and distracting tones were
characterized by their interaural time difference (ITD), interaural level
difference (ILD), or both ITD and ILD. The larger the ITD or ILD was, the better
similarity-based IM was overcome. If both interaural differences were applied to
standard/deviant tones, the release from IM was larger than when either
interaural difference was used. The results show that binaural cues are potent
cues to abolish similarity-based IM and that the auditory system makes use of
multiple available cues.
PMID- 26413723
TI - Age-related impairments in object-place associations are not due to hippocampal
dysfunction.
AB - Age-associated cognitive decline can reduce an individual's quality of life. As
no single neurobiological deficit can account for the wide spectrum of behavioral
impairments observed in old age, it is critical to develop an understanding of
how interactions between different brain regions change over the life span. The
performance of young and aged animals on behaviors that require the hippocampus
and cortical regions to interact, however, has not been well characterized.
Specifically, the ability to link a spatial location with specific features of a
stimulus, such as object identity, relies on the hippocampus, perirhinal and
prefrontal cortices. Although aging is associated with dysfunction in each of
these brain regions, behavioral measures of functional change within the
hippocampus, perirhinal and prefrontal cortices in individual animals are often
not correlated. Thus, how dysfunction of a single brain region within this
circuit, such as the hippocampus, impacts behaviors that require communication
with the perirhinal and prefrontal cortices remains unknown. To address this
question, young and aged rats were tested on the interregion dependent object
place paired association task, as well as a hippocampal-dependent test of spatial
reference memory. This particular cohort of aged rats did not show deficits on
the hippocampal-dependent task, but were significantly impaired at acquiring
object-place associations relative to young. These data suggest that behaviors
requiring functional connectivity across different regions of the memory network
may be particularly sensitive to aging, and can be used to develop models that
will clarify the impact of systems-level dysfunction in the elderly.
PMID- 26413724
TI - Mnemonic discrimination of similar face stimuli and a potential mechanism for the
"other race" effect.
AB - Face recognition is an important component of successful social interactions in
humans. A large literature in social psychology has focused on the phenomenon
termed the "other race" (ORE) effect, the tendency to be more proficient with
face recognition within one's own ethnic group compared with other ethnic groups.
Several potential hypotheses have been proposed for this effect, including
perceptual expertise, social grouping, and holistic face processing. Recent work
on mnemonic discrimination (i.e., the ability to resolve mnemonic interference
among similar experiences) may provide a mechanistic account for the ORE. In the
current study, we examined how discrimination and generalization in the presence
of mnemonic interference may contribute to the ORE. We developed a database of
computerized faces divided evenly among ethnic origins (Black, Caucasian, East
Asian, South Asian), as well as morphed face stimuli that varied in the amount of
similarity to the original stimuli (30%, 40%, 50%, and 60% morphs). Participants
first examined the original unmorphed stimuli during study, then during test were
asked to judge the prior occurrence of repetitions (targets), morphed stimuli
(lures), and new stimuli (foils). We examined participants' ability to correctly
reject similar morphed lures and found that it increased linearly as a function
of face dissimilarity. We additionally found that Caucasian participants'
mnemonic discrimination-generalization functions were sharply tuned for Caucasian
faces but considerably less tuned for East Asian and Black faces. These results
suggest that expertise plays an important role in resolving mnemonic
interference, which may offer a mechanistic account for the ORE.
PMID- 26413725
TI - 2-((Benzimidazol-2-yl)thio)-1-arylethan-1-ones: Synthesis, crystal study and
cancer stem cells CD133 targeting potential.
AB - In order to develop a potent anti-tumor agent that can target both cancer stem
cells and the bulk of tumor cells, a series of 2-((benzimidazol-2-yl)thio)-1
arylethan-1-ones 5a-o was synthesized. All compounds were evaluated for their
anti-proliferative activity towards colon HT-29 cancer cell line. In addition,
their inhibitory effect against cell surface expression of CD133, a potent cancer
stem cells (CSCs) marker, in the same cells was evaluated by flow cytometry at 10
MUM. Compound 5l emerged as the most active anti-proliferative analog against HT
29 (IC50 = 18.83 +/- 1.37 MUM), that almost equipotent as 5-fluorouracil (IC50 =
15.83 +/- 1.63 MUM) with 50.11 +/- 4.05% inhibition effect on CD133 expression,
suggested dual targeted effect. Also, compounds 5h, 5j, 5k and 5m-o inhibited the
expression of CD133 with more than 50%. The SAR study pointed out the
significance of substitution of the pendent phenyl group with lipophilic electron
donating groups or replacing it by 2-thienyl or 2-furyl groups.
PMID- 26413727
TI - Novel techniques and future directions in molecular diagnosis of malaria in
resource-limited settings.
AB - Despite being preventable and treatable, malaria remains a global health concern
with approximately 1.2 billion people at high risk of being infected, 90% of whom
are in the resource-limited settings of sub-Saharan Africa. The continued decline
in malaria cases globally has rekindled the possibility of elimination in certain
regions. As humans constitute the main reservoir of malaria, prompt and accurate
diagnosis by microscopy or rapid diagnostic tests is part not only of effective
disease management but also of control measures. However, for malaria
elimination, more sensitive diagnostic tools are needed to detect asymptomatic
and sub-microscopic infections that contribute to transmission. Molecular
techniques, which involve amplification of nucleic acids, are being developed and
modified to suit this purpose. This report provides a summary of the nucleic acid
amplification tests that are currently available for diagnosis of malaria, with
current improvements and adaptations for use in resource-limited settings.
PMID- 26413726
TI - H2O-mediated isatin spiro-epoxide ring opening with NaCN: Synthesis of novel 3
tetrazolylmethyl-3-hydroxy-oxindole hybrids and their anticancer evaluation.
AB - A simple method for isatin spiro-epoxide ring-opening by sodium cyanide in water
to obtain a variety of isatin hydroxy nitriles has been developed. Further, these
intermediates have been converted into new 3-tetrazolylmethyl-3-hydroxy-oxindole
hybrids via azide-nitrile cycloaddition reaction in a sealed tube. These
compounds were evaluated for their in vitro anticancer activity on five human
cancer cell lines i.e. breast (BT549 and MDA MB-231), prostate (PC-3 and DU-145)
and ovarian (PA-1). The compounds 6d and 6r showed potent anticancer activity
against DU-145 cell line with IC50 values in the range of 7.01 +/- 0.91 and 4.26
+/- 0.09 MUM respectively. The compounds 6d, 6g, 6q and 6r were also tested on
human normal prostate epithelial (RWPE-1) cells and found to be safer with lesser
cytotoxicity. The morphology and long term clonogenic survival of DU-145 cells
were severely affected by compound 6r. Cell cycle analysis revealed that the
compounds arrest the cells in G2/M phase. Acridine orange/ethidium bromide
(AO/EB) staining, DAPI staining, annexin-V binding assay and DNA fragmentation
analysis showed that cell proliferation was inhibited through induction of
apoptosis. Moreover, one of the compounds 6r treatment led to collapse of the
mitochondrial membrane potential (DPsim) and increased levels of reactive oxygen
species (ROS) in DU-145 cells.
PMID- 26413728
TI - Ab Initio Reaction Kinetics of CH3OC(?O) and CH2OC(?O)H Radicals.
AB - The dissociation and isomerization kinetics of the methyl ester combustion
intermediates methoxycarbonyl radical (CH3OC(?O)) and (formyloxy)methyl radical
(CH2OC(?O)H) are investigated theoretically using high-level ab initio methods
and Rice-Ramsperger-Kassel-Marcus (RRKM)/master equation (ME) theory. Geometries
obtained at the hybrid density functional theory (DFT) and coupled cluster
singles and doubles with perturbative triples correction (CCSD(T)) levels of
theory are found to be similar. We employ high-level ab initio wave function
methods to refine the potential energy surface: CCSD(T), multireference singles
and doubles configuration interaction (MRSDCI) with the Davidson-Silver (DS)
correction, and multireference averaged coupled-pair functional (MRACPF2) theory.
MRSDCI+DS and MRACPF2 capture the multiconfigurational character of transition
states (TSs) and predict lower barrier heights than CCSD(T). The temperature- and
pressure-dependent rate coefficients are computed using RRKM/ME theory in the
temperature range 300-2500 K and a pressure range of 0.01 atm to the high
pressure limit, which are then fitted to modified Arrhenius expressions.
Dissociation of CH3OC(?O) to CH3 and CO2 is predicted to be much faster than
dissociating to CH3O and CO, consistent with its greater exothermicity.
Isomerization between CH3OC(?O) and CH2OC(?O)H is predicted to be the slowest
among the studied reactions and rarely happens even at high temperature and high
pressure, suggesting the decomposition pathways of the two radicals are not
strongly coupled. The predicted rate coefficients and branching fractions at
finite pressures differ significantly from the corresponding high-pressure-limit
results, especially at relatively high temperatures. Finally, because it is one
of the most important CH3O removal mechanisms under atmospheric conditions, the
reaction kinetics of CH3O + CO was also studied along the PES of CH3OC(?O); the
resulting kinetics predictions are in remarkable agreement with experiments.
PMID- 26413729
TI - Patient response to insurer-led intervention for medication adherence - a pilot
study based on claims data in Korea.
AB - OBJECTIVE: This study was designed to investigate patient responses to a
medication counseling intervention program piloted by the National Health
Insurance Service (NHIS), the national health insurer in Korea, to improve
medication management in patients with hypertension, hyperlipidemia, or diabetes.
METHODS AND MATERIALS: Interventions were conducted from July to September 2013
through direct mailing followed by two telephone-initiated counseling sessions
for the medication discontinuation group (< 80% medication possession ratio (MPR)
and >= 2 months of discontinuation) and the medication over-possession group (>=
150% MPR). The telephone intervention was applied through two models: model 1
(counseling by NHIS staff only) and model 2 (counseling by NHIS staff with
contract-based working pharmacists in community pharmacies). Multivariate
logistic regression analysis was performed to identify factors affecting
favorable responses of patients to the telephone-initiated intervention. Patient
responses to the telephone-initiated intervention were evaluated by a counselor.
RESULTS: In all, 891 patients were counseledvia telephone. Patient responses to
the telephone-initiated intervention were favorablein 57.6%, neutral in 17.4% and
not favorable in 24.9% overall. Counseling by NHIS staff together with
pharmacists (model 2) produced more favorable responses from patients than
counseling by NHIS staff alone (model 1) (OR 2.73, 95% CI 1.97 - 3.77).
CONCLUSION: Our findings of favorable responses to interventions support a
personalized approach by the NHIS to improve patient behavior for medication
adherence.
PMID- 26413730
TI - Dealing with the high cost of biological therapies: developing and implementing a
biological therapy prioritization protocol for ankylosing spondylitis patients in
a tertiary hospital.
AB - OBJECTIVE: In January 2011, a biological therapies commission was created in our
hospital to fully address the management of biological drugs. A biological
therapy prioritization protocol was developed for ankylosing spondylitis (AS)
patients. Here, we describe it and report on its economic impact to illustrate
how we are optimizing the use of these expensive new drugs. METHODS: The
biological therapies commission established several procedures for the rational
use of biological drugs such as cost-efficiency therapeutic protocols,
pharmacovigilance, and therapeutic drug monitoring programs. The AS protocol was
based on clinical and economic aspects. We estimated the economic impact of the
protocol by comparing the cost of treating AS patients with biological drugs in
the pre-commission (2009 - 2010) vs. post-commission period (2011 - 2013). AS
patients treated with adalimumab (ADA), etanercept (ETN) or infliximab (IFX) for
at least 6 months in the 2009 - 2013 period were included. RESULTS: 107 patients
were included. In the pre-commission period, total expenses increased by +30,944
Euro (+4%). After protocol implementation, total expenses decreased by 11,441
Euro (-1%) during 2011, and by an additional 36,781 Euro (-4%) and 53,872 Euro (
8%) in 2012 and 2013, respectively. In the 2010 - 2013 period the cost of
biological therapy per patient-year decreased by 869A a?!, suggesting the
positive effects of the biological therapy prioritization protocol instauration.
CONCLUSION: We describe the establishment of a multidisciplinary biological
therapy commission to optimize the use of biological therapies. We illustrate its
work in developing a protocol for the management of AS patients with such
therapies. We show that after 3-years of implementation, the biological therapy
prioritization protocol allowed us to steadily decrease the direct cost of
biological drug therapies per patient, up to 869 Euro.
PMID- 26413731
TI - Pharmacokinetic and pharmacodynamic study of dexmedetomidine in elderly patients
during spinal anesthesia.
AB - OBJECTIVE: The application of dexmedetomidine in patient sedation is generally
accepted, though its clinical application is limited because of the lack of
information detailing the specific properties among diverse populations of
patients. The aim of this study was to compare the pharmacokinetic and
pharmacodynamic characteristics of dexmedetomidine between elderly and young
patients during spinal anesthesia. METHODS: 34 subjects (elderly group: n = 15;
young group: n = 19) with spinal anesthesia were enrolled in the present study
following the inclusion/exclusion criteria detailed below. All subjects received
intravenous infusion of dexmedetomidine with a loading dose of 0.5 ug x kg-1 for
10 minutes and a maintenance dose of 0.5 ug x kg-1 x h-1 for 50 minutes. Plasma
concentrations of dexmedetomidine were detected by the HPLC-MS/MS method and
pharmacokinetic parameters were calculated using WinNolin software. RESULTS:
There was no significant difference between the elderly and young subjects in
major pharmacokinetic parameters. There was a marked gender difference in the
Cmax (peak plasma concentration) and tmax (time to reach Cmax) between genders in
elderly subjects, though in this cohort the other pharmacokinetic parameters were
not significantly different. In the young subjects there were no noteworthy
variations between genders in pharmacokinetic parameters. There was no
significant difference between the two groups in BISAUC(0-t) (the area under the
bispectral index-time curve from time 0 to t hours), BISmin (the minimum value of
the bispectral index after drug delivery), and or tmin-BIS (bispectral index for
the minimum value of time). SBP (systolic blood pressure), DBP (diastolic blood
pressure), HR (heart rate), and SpO2(pulse oxygen saturation) developed
substantive differences in a time-dependent manner, but there were no
statistically significant differences in these four indicators in the time*group
at three time points (1 hour, 2 hours, and 3 hours after drug administration);
while SBP was significantly different between the groups, this differential
declined in a time-dependent manner, and there were no significant attendant
differences in the D-value. The observed values and D-values of DBP and HR were
similar in the groups, but the observed value and D-value of SpO2did differ.
There were 14 drug-related adverse events in the young group, and 26 drug-related
adverse events in the elderly group, a 46% differential. The percentage of
patients who requiring intervention during surgery was 68.75% (11/16) in the
elderly group and 36.84% (7/19) in the young group, with no significant
difference between the two groups once age was factored in (p = 0.06). None of
the pharmacodynamic indices, however, correlated with the key pharmacokinetic
parameters (Cmax, AUC(0->t), AUC(0->infinity)) of dexmedetomidine. CONCLUSIONS:
The clearance of dexmedetomidine in elderly patients showed a declining trend
compared to young patients. Interventions in the elderly group were more frequent
than in the young group, and the elderly group showed significant adverse
effects. It is suggested that elderly patients who use dexmedetomidine may
benefit from a different dose. However, further research with a larger population
size is required to confirm these findings.
PMID- 26413732
TI - Pharmacotherapeutic aspect of antibiotic therapy during acute community-acquired
pneumonia in adults at the University Hospital of Cocody (Abidjan).
AB - OBJECTIVE: Acute community-acquired pneumonia in Cote d'Ivoire, mainly in the
pneumology units, is the second most common cause of hospitalization after
tuberculosis. This study aimed to evaluate the compliance of antibiotic therapy
during bacterial acute community-acquired pneumonia with international guidelines
serving as frame of reference at the University Hospital of Cocody. MATERIALS AND
METHODS: We carried out a descriptive retrospective and analytic study on 62
hospitalized patients from December 1, 2008 to November 30, 2010 in the
Pneumophtisiology department at the University Hospital of Cocody (Abidjan). The
prescription of antibiotics was compared with the recommendations of the 15th
consensus conference on anti-infectious therapy by the Societe de Pathologie
Infectieuse de Langue Francaise (SPILF) (French Speaking Society of Infectious
Pathology) held in 2006. RESULTS: The main antibiotics prescribed were
amoxicillin-clavulanic acid (42.27%), netilmicin (34.5%) and ciprofloxacin (6%).
The antibiotic therapy diagrams were dominated by an antibiotic bitherapy; the
association of amoxicillin-clavulanic acid+netilmicin was observed in 80.64% of
the prescriptions. An antibiotic monotherapy was reported in 14.52% of the
prescriptions. Apyrexia at 72 hours was obtained with 64% of the patients with
nonstop antibiotic treatment, 24% of them presented a lack of apyrexia, and 12%
of them died. The lack of apyrexia at 72 hours treatment correlated with
concomitant administration of cotrimoxazole with prophylactic doses among HIV
positive patients. The level of the compliance with the SPILF recommendations is
low (3.6%). CONCLUSION: Thus, our results convey the necessity to draw up
national recommendations because of the specific realities of countries with
limited incomes.
PMID- 26413733
TI - Oscar Marin: A Daughter's Perspective.
PMID- 26413734
TI - Why I Honor Oscar Marin.
PMID- 26413735
TI - Neurologist, Cognitive Neuroscientist, Inspirer of Psychologists, and Humanist:
An Appreciation of Oscar Marin.
PMID- 26413736
TI - The Marin Lab at the Dawn of Cognitive Neuropsychology.
AB - This essay discusses the intellectual developments in psychology, linguistics,
and behavioral neurology that shaped Oscar Marin's approach to disorders of high
cortical function. As Chief of Neurology at Baltimore City Hospitals in the
1970s, Dr Marin teamed with biopsychologist Eleanor Saffran and the author in
seminal studies of acquired language disorders (aphasia) centering on core
processes of syntax and semantics, and rejecting premature reductionism. The
philosophical and methodological principles that motivated these studies are
traced through the author's personal recollections and the published writings of
the Marin lab. These principles came to be associated with the cognitive
neuropsychology school of research and have important linkages to contemporary
work in the neuroscience of aphasia and related cognitive disorders.
PMID- 26413737
TI - Oscar Marin: The Phenomenology of Mentoring.
PMID- 26413738
TI - Oscar Marin and the Creation of a Cognitive Neuropsychology Laboratory.
AB - During the 1980s, the Cognitive Neuropsychology Laboratory at Good Samaritan
Hospital, Portland, Oregon, made important strides in the study of brain injury.
Created and headed by Oscar Marin and the author, in affiliation with the
University of Oregon, the lab brought together students, fellows, and visiting
experts in neurology, psychology, psychiatry, neuropsychology, neurobiology,
neurophysiology, and computation. Their patient-focused collaborations produced
groundbreaking research in language and its disorders, bradyphrenia, neglect,
cerebellar function and impairment, and the psychology of music. The lab hosted
the meeting that they documented in the influential 1985 book Attention and
Performance XI: Mechanisms of Attention. The lab's members have gone on to lead
distinguished careers and continue making major contributions to cognitive
neuroscience.
PMID- 26413739
TI - What Oscar Marin Taught Me.
PMID- 26413740
TI - A Visit with Oscar and Clara Marin.
PMID- 26413741
TI - Revisiting the Single-Case Approach to Studying Reading Disorders.
AB - Oscar Marin was a neurologist with a remarkably broad interest in the brain and
its function. He was passionate about understanding how the brain processes
language and about helping people with acquired language disorders through his
science-based practice. Here we honor his memory by presenting a review and
commentary charting the cycle of neuroscientific approaches to studying reading
disorders over the past century. During this time, "best practices" have changed
from individual case studies to group studies and mega-studies and back again to
individual studies. We show how, across decades and almost unimaginable advances
in neuroimaging technology, the individual approach taken by Oscar Marin has
retained its importance.
PMID- 26413743
TI - Neuropsychological Thoughts, Then and Now: A Tribute to Oscar Marin.
AB - This brief paper, inspired by an invitation to acknowledge and celebrate Oscar
Marin's great contributions to cognitive neurology and neuropsychology, reviews
the case of a patient, T.P., who had significant deficits of naming, reading, and
spelling. I first studied and reported this patient 35 years ago, in 1979, when I
was significantly influenced by the work of Oscar Marin and his colleagues. I
have recently had the unusual opportunity to do some brief reassessment of T.P.'s
current (2015) cognitive abilities, and to reassess the interpretations that I
had given to her pattern of impairment in the initial studies. I suggest that
advances over the last decade or so-in theorizing about, and connectionist
modeling of, reading and spelling disorders-enable a more coherent account of
T.P.'s acquired anomia, dyslexia, and dysgraphia, and the relationships among
them.
PMID- 26413742
TI - Alzheimer Lesions in the Autopsied Brains of People 30 to 50 Years of Age.
AB - OBJECTIVE: To test the hypothesis that asymptomatic Alzheimer disease lesions may
appear before 50 years of age. BACKGROUND: Alzheimer disease has an asymptomatic
stage during which people are cognitively intact despite having substantial
pathologic changes in the brain. While this asymptomatic stage is common in older
people, how early in life it may develop has been unknown. METHODS: We
microscopically examined the postmortem brains of 154 people aged 30 to 39 years
(n=59) and 40 to 50 years (n=95) for specific Alzheimer lesions: beta-amyloid
plaques, neurofibrillary tangles, and tau-positive neurites. We genotyped DNA
samples for the apolipoprotein E gene (APOE). RESULTS: We found beta-amyloid
lesions in 13 brains, all of them from people aged 40 to 49 with no history of
dementia. These plaques were of the diffuse type only and appeared throughout the
neocortex. Among these 13 brains, five had very subtle tau lesions in the
entorhinal cortex and/or hippocampus. All individuals with beta-amyloid deposits
carried one or two APOE4 alleles. Among the individuals aged 40 to 50 with
genotype APOE3/4, 10 (36%) had beta-amyloid deposits but 18 (64%) had none.
CONCLUSIONS: Our study demonstrates that beta-amyloid deposits in the cerebral
cortex appear as early as 40 years of age in APOE4 carriers, suggesting that
these lesions may constitute a very early stage of Alzheimer disease. Future
preventive and therapeutic measures for this disease may have to be stratified by
risk factors like APOE genotype and may need to target people in their 40s or
even earlier.
PMID- 26413744
TI - Functional Mapping of the Human Auditory Cortex: fMRI Investigation of a Patient
with Auditory Agnosia from Trauma to the Inferior Colliculus.
AB - OBJECTIVE: To use functional magnetic resonance imaging to map the auditory
cortical fields that are activated, or nonreactive, to sounds in patient M.L.,
who has auditory agnosia caused by trauma to the inferior colliculi. BACKGROUND:
The patient cannot recognize speech or environmental sounds. Her discrimination
is greatly facilitated by context and visibility of the speaker's facial
movements, and under forced-choice testing. Her auditory temporal resolution is
severely compromised. Her discrimination is more impaired for words differing in
voice onset time than place of articulation. Words presented to her right ear are
extinguished with dichotic presentation; auditory stimuli in the right hemifield
are mislocalized to the left. METHODS: We used functional magnetic resonance
imaging to examine cortical activations to different categories of meaningful
sounds embedded in a block design. RESULTS: Sounds activated the caudal sub-area
of M.L.'s primary auditory cortex (hA1) bilaterally and her right posterior
superior temporal gyrus (auditory dorsal stream), but not the rostral sub-area
(hR) of her primary auditory cortex or the anterior superior temporal gyrus in
either hemisphere (auditory ventral stream). CONCLUSIONS: Auditory agnosia
reflects dysfunction of the auditory ventral stream. The ventral and dorsal
auditory streams are already segregated as early as the primary auditory cortex,
with the ventral stream projecting from hR and the dorsal stream from hA1. M.L.'s
leftward localization bias, preserved audiovisual integration, and phoneme
perception are explained by preserved processing in her right auditory dorsal
stream.
PMID- 26413746
TI - The Use of Surrogate Data in Demographic Population Viability Analysis: A Case
Study of California Sea Lions.
AB - Reliable data necessary to parameterize population models are seldom available
for imperiled species. As an alternative, data from populations of the same
species or from ecologically similar species have been used to construct models.
In this study, we evaluated the use of demographic data collected at one
California sea lion colony (Los Islotes) to predict the population dynamics of
the same species from two other colonies (San Jorge and Granito) in the Gulf of
California, Mexico, for which demographic data are lacking. To do so, we
developed a stochastic demographic age-structured matrix model and conducted a
population viability analysis for each colony. For the Los Islotes colony we used
site-specific pup, juvenile, and adult survival probabilities, as well as birth
rates for older females. For the other colonies, we used site-specific pup and
juvenile survival probabilities, but used surrogate data from Los Islotes for
adult survival probabilities and birth rates. We assessed these models by
comparing simulated retrospective population trajectories to observed population
trends based on count data. The projected population trajectories approximated
the observed trends when surrogate data were used for one colony but failed to
match for a second colony. Our results indicate that species-specific and even
region-specific surrogate data may lead to erroneous conservation decisions.
These results highlight the importance of using population-specific demographic
data in assessing extinction risk. When vital rates are not available and
immediate management actions must be taken, in particular for imperiled species,
we recommend the use of surrogate data only when the populations appear to have
similar population trends.
PMID- 26413745
TI - Plaque2.0-A High-Throughput Analysis Framework to Score Virus-Cell Transmission
and Clonal Cell Expansion.
AB - Classical plaque assay measures the propagation of infectious agents across a
monolayer of cells. It is dependent on cell lysis, and limited by user-specific
settings and low throughput. Here, we developed Plaque2.0, a broadly applicable,
fluorescence microscopy-based high-throughput method to mine patho-biological
clonal cell features. Plaque2.0 is an open source framework to extract
information from chemically fixed cells by immuno-histochemistry or RNA in situ
hybridization, or from live cells expressing GFP transgene. Multi-parametric
measurements include infection density, intensity, area, shape or location
information at single plaque or population levels. Plaque2.0 distinguishes lytic
and non-lytic spread of a variety of DNA and RNA viruses, including vaccinia
virus, adenovirus and rhinovirus, and can be used to visualize simultaneous
plaque formation from co-infecting viruses. Plaque2.0 also analyzes clonal growth
of cancer cells, which is relevant for cell migration and metastatic invasion
studies. Plaque2.0 is suitable to quantitatively analyze virus infections, vector
properties, or cancer cell phenotypes.
PMID- 26413747
TI - Mutational Heterogeneity in p6 Gag Late Assembly (L) Domains in HIV-1 Subtype C
Viruses from South Africa.
AB - Contradictory results have been reported on the impact of duplications/insertions
in the HIV-1 gag-p6 late assembly domains [TSG101-binding P(T/S)APP motif and
ALIX-binding LYPxnLxxL motif] heterogeneity following therapy failure. However,
most studies are limited to small numbers of patients and do not include samples
from South Africa, which has the largest number of HIV-1C-infected patients (HIV
1CZA). In this study we compared the gag-p6 variability among HIV-1CZA-infected
patients from a South African clinical cohort who experienced antiretroviral
therapy (ART) failure (n = 845) with ART-naive HIV-1CZA sequences (n = 706)
downloaded from the Los Alamos database. Partial (PTA/PTV/APP) or complete
P(T/S)APP duplications were less frequent in HIV-1CZA with ART failure compared
to therapy-naive ones (14% vs. 30%; p < 0.001). In contrast, the tetrapeptide
PYxE insertion, recently described by us, occurred more frequently (5-fold) in
therapy-failure patients (p < 0.001) and was associated with a higher number of
reverse transcriptase inhibitor (RTI) mutations (p = 0.04) among patients failing
ART.
PMID- 26413748
TI - On the Inference of Functional Circadian Networks Using Granger Causality.
AB - Being able to infer one way direct connections in an oscillatory network such as
the suprachiastmatic nucleus (SCN) of the mammalian brain using time series data
is difficult but crucial to understanding network dynamics. Although techniques
have been developed for inferring networks from time series data, there have been
no attempts to adapt these techniques to infer directional connections in
oscillatory time series, while accurately distinguishing between direct and
indirect connections. In this paper an adaptation of Granger Causality is
proposed that allows for inference of circadian networks and oscillatory networks
in general called Adaptive Frequency Granger Causality (AFGC). Additionally, an
extension of this method is proposed to infer networks with large numbers of
cells called LASSO AFGC. The method was validated using simulated data from
several different networks. For the smaller networks the method was able to
identify all one way direct connections without identifying connections that were
not present. For larger networks of up to twenty cells the method shows excellent
performance in identifying true and false connections; this is quantified by an
area-under-the-curve (AUC) 96.88%. We note that this method like other Granger
Causality-based methods, is based on the detection of high frequency signals
propagating between cell traces. Thus it requires a relatively high sampling rate
and a network that can propagate high frequency signals.
PMID- 26413749
TI - Spironolactone for People Age 70 Years and Older With Osteoarthritic Knee Pain: A
Proof-of-Concept Trial.
AB - OBJECTIVE: To determine whether spironolactone could benefit older people with
osteoarthritis (OA), based on a previous study showing that spironolactone
improved quality of life. METHODS: This parallel-group, randomized, placebo
controlled, double-blind trial randomized community-dwelling people ages >=70
years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or
matching placebo. The primary outcome was between-group difference in change in
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain
subscale scores. Secondary outcomes included WOMAC stiffness and physical
function subscores, EuroQol 5-domain (EQ-5D) 3L score, and mechanistic markers.
Analysis was by intent to treat, using mixed-model regression, adjusting for
baseline values of test variables. RESULTS: A total of 421 people had eligibility
assessed, and 86 were randomized. Mean +/- SD age was 77 +/- 5 years and 53 of 86
(62%) were women. Adherence to study medication was 99%, and all participants
completed the 12-week assessment. No significant improvement was seen in the
WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval
(95% CI) - 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score
(0.2 points [95% CI -0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0
points [95% CI -0.7, 0.8]; P = 0.98), or EQ-5D 3L score (0.04 points [95% CI
0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C
telopeptide of type II collagen were not significantly different between groups.
More minor adverse events were noted in the spironolactone group (47 versus 32),
but no increase in death or hospitalization was evident. CONCLUSION:
Spironolactone did not improve symptoms, physical function, or health-related
quality of life in older people with knee OA.
PMID- 26413750
TI - LYAR promotes colorectal cancer cell mobility by activating galectin-1
expression.
AB - Colorectal cancer (CRC) is one of the leading causes of cancer-related death
worldwide. However, the molecular mechanisms of CRC pathogenesis are not fully
understood. In this study, we report the characterization of LYAR (Ly-1 antibody
reactive clone) as a key regulator of the migration and invasion of human CRC
cells. Immunohistochemistry analysis demonstrated that LYAR is expressed at a
higher level in metastatic CRC tissues. We found that LYAR promoted the migratory
and invasive capabilities of CRC cells. Gene expression profile analysis of CRC
cells showed that LGALS1, which encodes the galectin-1 protein, was a potential
target of LYAR. The ChIP assay and gene reporter assays indicated that LYAR
directly bound to the LGALS1 promoter. The ectopic expression of galectin-1
partially restored the mobile potential of LYAR knocked-down cells, which
suggests that galectin-1 contributed to the LYAR-promoted cell migration and
invasion of CRC cells. Thus, this study revealed a novel mechanism by which the
transcription factor LYAR may promote tumor cell migration and invasion by
upregulating galectin-1 gene expression in CRC.
PMID- 26413751
TI - Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic
reprogram and greater stem-like properties in LnCap prostate cancer cells in
vitro.
AB - Aerobic glycolysis is one of the important hallmarks of cancer cells and
eukaryotic cells. In this study, we have investigated the relationship between
blocking mitochondrial pyruvate carrier (MPC) with UK5099 and the metabolic
alteration as well as stemness phenotype of prostatic cancer cells. It was found
that blocking pyruvate transportation into mitochondrial attenuated mitochondrial
oxidative phosphorylation (OXPHOS) and increased glycolysis. The UK5099 treated
cells showed significantly higher proportion of side population (SP) fraction and
expressed higher levels of stemness markers Oct3/4 and Nanog. Chemosensitivity
examinations revealed that the UK5099 treated cells became more resistant to
chemotherapy compared to the non-treated cells. These results demonstrate
probably an intimate connection between metabolic reprogram and stem-like
phenotype of LnCap cells in vitro. We propose that MPC blocker (UK5099)
application may be an ideal model for Warburg effect studies, since it attenuates
mitochondrial OXPHOS and increases aerobic glycolysis, a phenomenon typically
reflected in the Warburg effect. We conclude that impaired mitochondrial OXPHOS
and upregulated glycolysis are related with stem-like phenotype shift in
prostatic cancer cells.
PMID- 26413752
TI - Phased-array combination for MR spectroscopic imaging using a water reference.
AB - PURPOSE: To evaluate methods for multichannel combination of three-dimensional MR
spectroscopic imaging (MRSI) data with a focus on using information from a water
reference spectroscopic image. METHODS: Volumetric MRSI data were acquired for a
phantom and for human brain using 8- and 32-channel detection. Acquisition
included a water-reference dataset that was used to determine the weights for
several multichannel combination methods. Results were compared using the signal
to-noise ratio (SNR) of the N-acetylaspartate resonance. RESULTS: Performance of
all methods was very similar for the phantom study, with the whitened singular
value decomposition (WSVD) and signal magnitude (S) weighting combination having
a small advantage. For in vivo studies, the S weighting, SNR weighting and signal
to noise squared (S/N(2) ) weighting were the three best methods and performed
similarly. Example spectra and SNR maps indicated that the SVD and WSVD methods
tend to fail for voxels at the outer edges of the brain that include strong lipid
signal contributions. CONCLUSION: For data combination of MRSI data using water
reference information, the S/N(2) weighting, SNR and S weighting were the best
methods in terms of spectral quality SNR. These methods are also computationally
efficient and easy to implement. Magn Reson Med 76:733-741, 2016. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26413754
TI - The Mechanics of Morality.
PMID- 26413753
TI - Identification of ILK as a novel therapeutic target for acute and chronic myeloid
leukemia.
AB - Current treatment options as well as clinical efficacy are limited for chronic
myelogenous leukemia (CML), Ph+ acute lymphoblastic leukemia (ALL), and acute
myeloid leukemia (AML). In response to the pressing need for more efficacious
treatment approaches and strategies to override drug resistance in advanced stage
CML, Ph+ ALL, and AML, we investigated the effects of inhibition of ILK as a
potentially novel and effective approach to treatment of these challenging
malignancies. Using the small molecule ILK inhibitor, Cpd22, and ILK knockdown,
we investigated the importance of ILK in the growth and viability of leukemia.
Our results suggest that the ILK inhibition may be an effective treatment for
CML, Ph+ ALL, and AML as a single therapy, with ILK expression levels positively
correlating with the efficacy of ILK inhibition. The identification of ILK as a
novel target for leukemia therapy warrants further investigation as a therapeutic
approach that could be of potential clinical benefit in both acute and chronic
myeloid leukemias.
PMID- 26413755
TI - The Author Replies.
PMID- 26413756
TI - Normalizing Aid-in-Dying within the Practice of Medicine.
PMID- 26413757
TI - Giving Up My Naivete.
PMID- 26413758
TI - Justice Roberts Gets It.
PMID- 26413759
TI - Warm and Dead?
PMID- 26413760
TI - Limits of Responsibility: Genome Editing, Asilomar, and the Politics of
Deliberation.
PMID- 26413761
TI - Why Training in Ecological Research Must Incorporate Ethics Education.
PMID- 26413762
TI - Teaching Bioethics at the Secondary School Level.
PMID- 26413763
TI - Bridging the Gap between Knowledge and Skill: Integrating Standardized Patients
into Bioethics Education.
PMID- 26413765
TI - Having Conversations about Organ Donation.
PMID- 26413766
TI - Looking for experts (a call for essays).
PMID- 26413767
TI - Predictors of Hypopituitarism in Patients with Traumatic Brain Injury.
AB - Hypopituitarism may often occur in association with traumatic brain injury (TBI).
Identification of reliable predictors of pituitary dysfunction is of importance
in order to establish a rational testing approach. We searched the records of
patients with TBI, who underwent neuroendocrine evaluation in our institution
between 2007 and 2013. One hundred sixty-six adults (70% men) with TBI (median
age: 41.6 years; range: 18-76) were evaluated at a median interval of 40.4 months
(0.2-430.4).Of these, 31% had >=1 pituitary deficiency, including 29% of patients
with mild TBI and 35% with moderate/severe TBI. Growth hormone deficiency was the
most common deficiency (21%); when body mass index (BMI)-dependent cutpoints were
used, this was reduced to 15%. Central hypoadrenalism occurred in10%, who were
more likely to have suffered a motor vehicle accident (MVA, p = 0.04),
experienced post-traumatic seizures (p = 0.04), demonstrated any intracranial
hemorrhage (p = 0.05), petechial brain hemorrhages (p = 0.017), or focal cortical
parenchymal contusions (p = 0.02). Central hypothyroidism occurred in 8% and
central hypogonadism in 12%; the latter subgroup had higher BMI (p = 0.03), were
less likely to be working after TBI (p = 0.002), and had lower Global Assessment
of Functioning (GAF) scores (p = 0.03). Central diabetes insipidus (DI) occurred
in 6%, who were more likely to have experienced MVA (p < 0.001) or sustained
moderate/severe TBI (p < 0.001). Patients with MVA and those with post-traumatic
seizures, intracranial hemorrhage, petechial brain hemorrhages, and/or focal
cortical contusions are at particular risk for serious pituitary dysfunction,
including adrenal insufficiency and DI, and should be referred for neuroendocrine
testing. However, a substantial proportion of patients without these risk factors
also developed hypopituitarism.
PMID- 26413768
TI - Magnetoelectric Coupling Induced by Interfacial Orbital Reconstruction.
AB - Reversible orbital reconstruction driven by ferroelectric polarization modulates
the magnetic performance of model ferroelectric/ferromagnetic heterostructures
without onerous limitations. Mn-d(x2-y2) orbital occupancy and related
interfacial exotic magnetic states are enhanced and weakened by negative and
positive electric fields, respectively, filling the missing member-orbital in the
mechanism of magnetoelectric coupling and advancing the application of orbitals
to microelectronics.
PMID- 26413769
TI - Flexible goal attribution in early mindreading.
AB - The 2-systems theory developed by Apperly and Butterfill (2009; Butterfill &
Apperly, 2013) is an influential approach to explaining the success of infants
and young children on implicit false-belief tasks. There is extensive empirical
and theoretical work examining many aspects of this theory, but little attention
has been paid to the way in which it characterizes goal attribution. We argue
here that this aspect of the theory is inadequate. Butterfill and Apperly's
characterization of goal attribution is designed to show how goals could be
ascribed by infants without representing them as related to other psychological
states, and the minimal mindreading system is supposed to operate without
employing flexible semantic-executive cognitive processes. But research on infant
goal attribution reveals that infants exhibit a high degree of situational
awareness that is strongly suggestive of flexible semantic-executive cognitive
processing, and infants appear moreover to be sensitive to interrelations between
goals, preferences, and beliefs. Further, close attention to the structure of
implicit mindreading tasks--for which the theory was specifically designed-
indicates that flexible goal attribution is required to succeed. We conclude by
suggesting 2 approaches to resolving these problems.
PMID- 26413770
TI - Correction: Are Sex Drive and Hypersexuality Associated with Pedophilic Interest
and Child Sexual Abuse in a Male Community Sample?
PMID- 26413772
TI - Standardization of Free Thyroxine and Harmonization of Thyrotropin Measurements:
A Request for Input from Endocrinologists and Other Physicians.
PMID- 26413771
TI - Detecting acute mesenteric ischemia in CT of the acute abdomen is dependent on
clinical suspicion: Review of 95 consecutive patients.
AB - OBJECTIVES: (1) To evaluate the ability of emergency room radiologists to detect
acute mesenteric ischemia (AMI) from computed tomography (CT) images in patients
with acute abdominal pain. (2) To identify factors affecting radiologists'
performance in the CT interpretation and patient outcome. MATERIALS AND METHODS:
A retrospective study of 95 consecutive patients treated for 97 AMI events
between 2009 and 2013 was carried out. The etiology of AMI was embolism in 24
(25%), atherosclerotic vascular disease (ASVD) in 39 (40%), non-obstructive
mesenteric ischemia (NOMI) in 25 (26%), and mesenteric venous thrombosis (MVT) in
nine (9%) cases. The protocols, referrals and initial radiology reports of the
abdominal CTs were analyzed. The CT studies were further scrutinized for vascular
and intestinal findings. RESULTS: The referring clinician had suspected AMI in 30
(31%) cases prior to imaging. The crucial findings of AMI had been stated in 97%
of the radiology reports if the clinician had mentioned AMI suspicion in the
referral; if not, the corresponding rate was 81% (p=0.04). Patients without
suspicion of AMI prior to CT were more prone to undergo bowel resection. CT
protocol was optimal for AMI (with contrast enhancement in arterial and venous
phases) in only 34 (35%) cases. Intestinal findings were more difficult to detect
than vascular findings. Vascular findings were retrospectively detectable in 92%
of cases with embolism and 100% in ASVD and MVT. Some evidence of intestinal
abnormality was retrospectively found in the CT findings in 92%, 100%, 100% and
67% of cases with embolism, ASVD, NOMI and MVT, respectively. CONCLUSIONS: AMI is
underdiagnosed in the CT of the acute abdomen if there is no clinical suspicion.
PMID- 26413774
TI - A randomised control trial of the cognitive effects of working in a seated as
opposed to a standing position in office workers.
AB - Sedentary behaviour is increasing and has been identified as a potential
significant health risk, particularly for desk-based employees. The development
of sit-stand workstations in the workplace is one approach to reduce sedentary
behaviour. However, there is uncertainty about the effects of sit-stand
workstations on cognitive functioning. A sample of 36 university staff
participated in a within-subjects randomised control trial examining the effect
of sitting vs. standing for one hour per day for five consecutive days on
attention, information processing speed, short-term memory, working memory and
task efficiency. The results of the study showed no statistically significant
difference in cognitive performance or work efficiency between the sitting and
standing conditions, with all effect sizes being small to very small (all ds <
.2). This result suggests that the use of sit-stand workstations is not
associated with a reduction in cognitive performance. Practitioner Summary:
Although it has been reported that the use of sit-stand desks may help offset
adverse health effects of prolonged sitting, there is scant evidence about
changes in productivity. This randomised control study showed that there was no
difference between sitting and standing for one hour on cognitive function or
task efficiency in university staff.
PMID- 26413773
TI - HIV-1 Tropism Determines Different Mutation Profiles in Proviral DNA.
AB - In order to establish new infections HIV-1 particles need to attach to receptors
expressed on the cellular surface. HIV-1 particles interact with a cell membrane
receptor known as CD4 and subsequently with another cell membrane molecule known
as a co-receptor. Two major different co-receptors have been identified: C-C
chemokine Receptor type 5 (CCR5) and C-X-C chemokine Receptor type 4 (CXCR4)
Previous reports have demonstrated cellular modifications upon HIV-1 binding to
its co-receptors including gene expression modulations. Here we investigated the
effect of viral binding to either CCR5 or CXCR4 co-receptors on viral diversity
after a single round of reverse transcription. CCR5 and CXCR4 pseudotyped viruses
were used to infect non-stimulated and stimulated PBMCs and purified CD4 positive
cells. We adopted the SOLiD methodology to sequence virtually the entire proviral
DNA from all experimental infections. Infections with CCR5 and CXCR4 pseudotyped
virus resulted in different patterns of genetic diversification. CCR5 virus
infections produced extensive proviral diversity while in CXCR4 infections a more
localized substitution process was observed. In addition, we present pioneering
results of a recently developed method for the analysis of SOLiD generated
sequencing data applicable to the study of viral quasi-species. Our findings
demonstrate the feasibility of viral quasi-species evaluation by NGS
methodologies. We presented for the first time strong evidence for a host cell
driving mechanism acting on the HIV-1 genetic variability under the control of co
receptor stimulation. Additional investigations are needed to further clarify
this question, which is relevant to viral diversification process and consequent
disease progression.
PMID- 26413775
TI - Expression of NY-ESO-1 in Triple-Negative Breast Cancer Is Associated with Tumor
Infiltrating Lymphocytes and a Good Prognosis.
AB - OBJECTIVES: Accumulating evidence suggests that immunotherapy has great potential
for treating triple-negative breast cancer (TNBC). We analyzed the expression of
NY-ESO-1, which is a potent immunogenic cancer testis antigen, and its
association with clinicopathological factors in large cohorts of breast cancer
patients. METHODS: A total of 623 consecutive breast cancer patients who
underwent surgery between 1993 and 1998 and 612 TNBC patients who underwent
surgery between 2004 and 2010 at Asan Medical Center were included.
Immunohistochemical staining for NY-ESO-1 was performed using tissue microarrays.
RESULTS: NY-ESO-1 was expressed in 2.6% of consecutive breast cancers, all of
which were TNBC (p < 0.001). NY-ESO-1 expression was identified in 9.7% of the
TNBC cohort and was significantly correlated with a higher level of tumor
infiltrating lymphocytes (TIL; p = 0.026). In survival analyses, a lower level of
TIL (all, p < 0.001) and the absence of NY-ESO-1 expression (p = 0.024) were
significantly associated with poor disease-free survival. Additionally, positive
NY-ESO-1 expression was an independent favorable prognostic factor in TNBC
patients (p = 0.046). CONCLUSIONS: NY-ESO-1 is specifically expressed in TNBC,
and NY-ESO-1 expression is an independent good prognostic factor in TNBC.
Evaluation of NY-ESO-1 expression in TNBC might be useful for selecting patients
who may benefit from vaccination therapy and also has a prognostic significance
in TNBC.
PMID- 26413777
TI - VEGF-A mRNA measurement in meningiomas using a new simplified approach: branched
DNA and chemiluminescence.
AB - For decades, the preferred and almost sole method for measurement of gene
expression has been RT-qPCR. The method is robust, inexpensive, and well-studied;
however, PCR is also quite laborious and vulnerable to contamination. As part of
an investigation of VEGF-A gene expression in meningiomas, an alternative and
less laborious method for gene expression analysis based on branched DNA
hybridization and chemiluminescence (Lumistar) was tested. Albeit the two methods
differ, in principle, cellular mRNA-concentration is measured with both. Because
they both determine gene expression via the measurement of mRNA-concentration,
they were expected to be comparable. The aim of the present study was to compare
Lumistar to the traditional RT-qPCR approach in a routine laboratory setting,
where there is emphasis on rapid analysis response. Meningioma (nA =A 10) and
control brain tissue (nA =A 5) samples were collected and VEGF-A and GAPDH mRNA
were quantified using both RT-qPCR and Lumistar. Furthermore, two dilution series
of two of the meningioma samples were prepared in order to make quantitative
analyses. Both Lumistar and RT-qPCR-results were found to follow concentration
dependent linear paths when diluted (p < 0.0001 and p < 0.01). Finally, Lumistar
and RT-qPCR analyses were performed with the inclusion of a reference gene
(GAPDH), where similar results were obtained with the two methods (R2 = 0.48; p =
0.01). It is intriguing that in spite of the vast difference in handling and
assay principles, gene expression results are similar. The preferred method
depends on the variability of the samples, budget, and time. Lumistar was less
time consuming, while RT-qPCR was less expensive and best suited for data sets
with large sample variability.
PMID- 26413776
TI - Intimate-Partner and Client-Initiated Violence among Female Street-Based Sex
Workers in China: Does a Support Network Help?
AB - BACKGROUND: Globally, female street-based sex workers are vulnerable to gender
based violence. Previous research has shown having a peer social network can
reduce sex workers' risks of victimization. However, mechanisms of how social
network impacts violence among female street-based sex workers are still far from
clear. METHODS: Our study was based on data abstracted from a paper-and-pencil
survey administered among 218 female street-based sex workers in Shanghai, China.
We focused on self-reported client-initiated violence and intimate-partner
violence in emotional, physical, and sexual forms. Social networks were
characterized by the size and sources of financial and psychosocial support (e.g.
family, friends, and peers). Multi-variable logistic regression was used to
estimate adjusted odds ratios (AOR) of each type of violence exposure by social
network structure after the adjustment of age, education, and years in Shanghai.
RESULTS: The street-based female sex workers in our study were primarily rural-to
urban migrants (95.7%) with an average age of 41 years old. 24.3% and 62.8% of
the sex workers reported intimate-partner violence and client-initiated violence
respectively. Lack of financial support, as defined by having only one individual
or none in her peer support system to help financially, was significantly
associated with self-reported intimate-partner violence (AOR: 2.5; 95% CI: 1.1
5.9). Respondents who reported client-initiated violence, by contrast, were more
likely to report lacked psychosocial support from family (AOR: 2.2, 95% CI: 1.0
4.6) and peers (AOR: 5.1, 95% CI: 2.2-11). CONCLUSION: This study is one of the
first to systematically analyze the associations between social network and
gender-based violence among street-based female sex worker. We reported a high
prevalence of both types of gender-based violence and their complex associations
with family, friends, and peer support network. Policies with goals to reduce
violence against women may apply these findings to leverage social network in the
interventions against gender-based violence.
PMID- 26413778
TI - Pathology-confirmed cerebral arterial invasion and recurrent multiple brain
metastasis from cardiac myxoma without evidence of disease after surgery and
radiotherapy.
PMID- 26413779
TI - Bipolar Versus Monopolar Transurethral Resection of Nonmuscle-Invasive Bladder
Cancer: A Meta-Analysis.
AB - BACKGROUND AND PURPOSE: Bipolar energy has recently been used as a common
alternative to conventional monopolar transurethral resection of the bladder
(TURB) while managing nonmuscle-invasive bladder cancer (NMIBC). We established a
meta-analysis comparing the safety and efficacy of plasmakinetic bipolar and
monopolar TURB for NMIBC. METHODS: A systematic search of PubMed, MEDLINE, Web of
Science, and China National Knowledge Infrastructure was performed up to March 1,
2015. Outcomes of interest assessing the two techniques included demographic and
clinical baseline characteristics, perioperative variables, and complications.
RESULTS: Eight eligible trials evaluating bipolar TURB (bTURB) versus monopolar
TURB (mTURB) for NMIBC were identified including six randomized controlled trials
(RCTs), one prospective study, and one retrospective study. The bTURB was
associated with shorter operative time (P = 0.002), shorter hospital stay (P <
0.001), less established blood loss (P < 0.001), and shorter catheterization time
(P = 0.004). There were fewer complications such as obturator nerve reflex (P <
0.001) and bladder perforation (P = 0.003) in the bTURB group. The postoperative
recurrence rate in 2 years also showed advantages of bTURB over mTURB.
CONCLUSION: Our data showed that bTURB appeared to be a safe and efficient method
and had presented several advantages when compared with conventional mTURB in the
management of NMIBC. As a promising technique, bTURB may be used as a preferable
choice instead of mTURB for superficial bladder tumor.
PMID- 26413780
TI - Endogenous antigen processing drives the primary CD4+ T cell response to
influenza.
AB - By convention, CD4+ T lymphocytes recognize foreign and self peptides derived
from internalized antigens in combination with major histocompatibility complex
class II molecules. Alternative pathways of epitope production have been
identified, but their contributions to host defense have not been established. We
show here in a mouse infection model that the CD4+ T cell response to influenza,
critical for durable protection from the virus, is driven principally by
unconventional processing of antigen synthesized within the infected antigen
presenting cell, not by classical processing of endocytosed virions or material
from infected cells. Investigation of the cellular components involved, including
the H2-M molecular chaperone, the proteasome and gamma-interferon-inducible
lysosomal thiol reductase revealed considerable heterogeneity in the generation
of individual epitopes, an arrangement that ensures peptide diversity and broad
CD4+ T cell engagement. These results could fundamentally revise strategies for
rational vaccine design and may lead to key insights into the induction of
autoimmune and anti-tumor responses.
PMID- 26413782
TI - Colon Necrosis Due to Sodium Polystyrene Sulfonate with and without Sorbitol: An
Experimental Study in Rats.
AB - INTRODUCTION: Based on a single rat study by Lillemoe et al, the consensus has
been formed to implicate sorbitol rather than sodium polystyrene sulfonate (SPS)
as the culprit for colon necrosis in humans treated with SPS and sorbitol. We
tested the hypothesis that colon necrosis by sorbitol in the experiment was due
to the high osmolality and volume of sorbitol rather than its chemical nature.
METHODS: 26 rats underwent 5/6 nephrectomy. They were divided into 6 groups and
given enema solutions under anesthesia (normal saline, 33% sorbitol, 33%
mannitol, SPS in 33% sorbitol, SPS in normal saline, and SPS in distilled water).
They were sacrificed after 48 hours of enema administration or earlier if they
were very sick. The gross appearance of the colon was visually inspected, and
then sliced colon tissues were examined under light microscopy. RESULTS: 1 rat
from the sorbitol and 1 from the mannitol group had foci of ischemic colonic
changes. The rats receiving SPS enema, in sorbitol, normal saline, distilled
water, had crystal deposition with colonic necrosis and mucosal erosion. All the
rats not given SPS survived until sacrificed at 48 h whereas 11 of 13 rats that
received SPS in sorbitol, normal saline or distilled water died or were clearly
dying and sacrificed sooner. There was no difference between sorbitol and
mannitol when given without SPS. CONCLUSIONS: In a surgical uremic rat model, SPS
enema given alone or with sorbitol or mannitol seemed to cause colon necrosis and
high mortality rate, whereas 33% sorbitol without SPS did not.
PMID- 26413781
TI - Clinical translation of a high-performance neural prosthesis.
AB - Neural prostheses have the potential to improve the quality of life of
individuals with paralysis by directly mapping neural activity to limb- and
computer-control signals. We translated a neural prosthetic system previously
developed in animal model studies for use by two individuals with amyotrophic
lateral sclerosis who had intracortical microelectrode arrays placed in motor
cortex. Measured more than 1 year after implant, the neural cursor-control system
showed the highest published performance achieved by a person to date, more than
double that of previous pilot clinical trial participants.
PMID- 26413783
TI - Generation of human iPS cell line ihFib3.2 from dermal fibroblasts.
AB - The human ihFib3.2 iPS cell line was generated from dermal fibroblasts obtained
from a healthy donor. Lentiviral particles were produced with the polycistronic
hSTEMCCA vector with Oct4, Sox2, cMyc and Klf4 as reprogramming factors.
PMID- 26413784
TI - CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal
cells.
AB - Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal
stem cells) and their progenitors have been identified based on retrospective
functional criteria. CD markers are employed to define cell populations with
distinct functional characteristics. However, defining and prospective isolation
of BMSCs and committed progenitors are lacking. Here, we compared the
transcriptome profile of CD markers expressed at baseline and during the course
of osteoblast and adipocyte differentiation of two well-characterized osteogenic
committed murine BMSCs (mBMSC(Bone)) and adipogenic-committed mBMSCs
(mBMSC(Adipo)), respectively. Bioinformatic analysis revealed the presence of a
core set of canonical mBMSC CD markers with comparable expression levels in
mBMSC(Bone) and mBMSC(Adipo) at baseline and during their differentiation. We
identified 11 CD markers that are differentially expressed between mBMSC(Adipo)
and mBMSC(Bone). Among these, we identified osteoprogenitor-associated CD markers
expressed only in mBMSC(Bone): CD34, CD54, CD73, CD132, CD200, CD227 and
adipoprogenitor-associated CD markers expressed only in mBMSC(Adipo): CD53, CD80,
CD134, CD141 and CD212. FACS analysis confirmed these results. We selected CD34
for further analysis. CD34 was expressed at baseline of mouse stromal cell line
ST2, primary mBMSCs, mBMSC(Bone) and its expression decreased during osteoblast
differentiation. FACS-sorted CD34(+) primary mBMSCs exhibited higher expression
of 70% osteoblast-associated genes, and formed significantly higher heterotopic
bone in vivo when implanted subcutaneously in immune-deficient mice compared with
CD34(-) primary mBMSCs. Our results demonstrate that a set of CD markers can
distinguish osteoprogenitor versus adipoprogenitor populations of mBMSCs. CD34 is
suitable for prospective isolation of mouse bone marrow osteoprogenitors.
PMID- 26413785
TI - Amyotrophic lateral sclerosis models derived from human embryonic stem cells with
different superoxide dismutase 1 mutations exhibit differential drug responses.
AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron (MN)
disease. The gene encoding superoxide dismutase 1 (SOD1) is a causative element
of familial ALS. Animal ALS models involving SOD1 gene mutations are widely used
to study the underlying mechanisms of disease and facilitate drug discovery.
Unfortunately, most drug candidates have failed in clinical trials, potentially
due to species differences among rodents and humans. It is unclear, however,
whether there are different responses to drugs among the causative genes of ALS
or their associated mutations. In this study, to evaluate different SOD1
mutations, we generated SOD1-ALS models derived from human embryonic stem cells
with identical genetic backgrounds, except for the overexpression of mutant
variants of SOD1. The overexpression of mutant SOD1 did not affect pluripotency
or MN differentiation. However, mutation-dependent reductions in neurite length
were observed in MNs. Moreover, experiments investigating the effects of specific
compounds revealed that each ALS model displayed different responses with respect
to MN neurite length. These results suggest that SOD1 mutations could be
classified based the response of MNs to drug treatment. This classification could
be useful for the development of mutant-specific strategies for drug discovery
and clinical trials.
PMID- 26413786
TI - Establishment of leukemia inhibitory factor (LIF)-independent iPS cells with
potentiated Oct4.
AB - Leukemia inhibitory factor (LIF) is widely used to establish and maintain naive
pluripotent stem cells, including mouse embryonic stem cells (ESCs) and induced
pluripotent stem cells (iPSCs). Although the combination of chemical inhibitors
called 2i can establish mouse iPSCs without LIF from primed pluripotent stem
cells, it has been difficult, if not impossible, to establish mouse iPSCs from
differentiated somatic cells without LIF. We previously showed that the fusion
gene of the transactivation domain of MyoD and the full-length Oct4 (M3O)
increases the efficiency of making iPSCs when transduced into fibroblasts along
with Sox2, Klf4, and c-Myc (M3O-SKM). Here, we report that M3O-SKM allows for
establishment of iPSCs without exogenous LIF from mouse embryonic fibroblasts.
The established iPSCs remained undifferentiated and maintained pluripotency over
90 days without LIF as long as M3O was expressed. The iPSCs upregulated miR-205
5p, which was potentially involved in the LIF-independence by suppressing the two
signaling pathways inhibited by 2i. The result indicates that potentiated Oct4
can substitute for the LIF signaling pathway, providing a novel model to link
Oct4 and LIF, two of the most significant players in naive pluripotency.
PMID- 26413787
TI - E-Ras improves the efficiency of reprogramming by facilitating cell cycle
progression through JNK-Sp1 pathway.
AB - We have previously shown that pluripotent stem cells can be induced from adult
somatic cells which were exposed to protein extracts isolated from mouse
embryonic stem cells (mESC). Interestingly, generation of induced pluripotent
stem (iPS) cells depended on the background of ES cell lines; possible by
extracts from C57, but not from E14. Proteomic analysis of two different mES cell
lines (C57 and E14) shows that embryonic Ras (E-Ras) is expressed differently in
two mES cell lines; high level of E-Ras only in C57 mESC whose extracts allows
iPS cells production from somatic cells. Here, we show that E-Ras augments the
efficiency in reprogramming of fibroblast by promoting cell proliferation. We
found that over-expression of E-Ras in fibroblast increased cell proliferation
which was caused by specific up-regulation of cyclins D and E, not A or B,
leading to the accelerated G1 to S phase transition. To figure out the common
transcription factor of cyclins D and E, we used TRANSFAC database and selected
SP1 as a candidate which was confirmed as enhancer of cyclins D and E by
luciferase promoter assay using mutants. As downstream signaling pathways, E-Ras
activated only c-Jun N-terminal kinases (JNK) but not ERK or p38. Inhibition of
JNK prevented E-Ras-mediated induction of pSP1, cyclins D, E, and cell
proliferation. Finally, E-Ras transduction to fibroblast enhanced the efficiency
of iPS cell generation by 4 factors (Oct4/Klf4/Sox2/C-myc), which was prevented
by JNK inhibitor. In conclusion, E-Ras stimulates JNK, enhances binding of Sp1 on
the promoter of cyclins D and E, leading to cell proliferation. E-Ras/JNK axis is
a critical mechanism to generate iPS cells by transduction of 4 factors or by
treatment of mESC protein extracts.
PMID- 26413788
TI - Improving Maternal Care through a State-Wide Health Insurance Program: A Cost and
Cost-Effectiveness Study in Rural Nigeria.
AB - BACKGROUND: While the Nigerian government has made progress towards the
Millennium Development Goals, further investments are needed to achieve the
targets of post-2015 Sustainable Development Goals, including Universal Health
Coverage. Economic evaluations of innovative interventions can help inform
investment decisions in resource-constrained settings. We aim to assess the cost
and cost-effectiveness of maternal care provided within the new Kwara State
Health Insurance program (KSHI) in rural Nigeria. METHODS AND FINDINGS: We used a
decision analytic model to simulate a cohort of pregnant women. The primary
outcome is the incremental cost effectiveness ratio (ICER) of the KSHI scenario
compared to the current standard of care. Intervention cost from a healthcare
provider perspective included service delivery costs and above-service level
costs; these were evaluated in a participating hospital and using financial
records from the managing organisations, respectively. Standard of care costs
from a provider perspective were derived from the literature using an ingredient
approach. We generated 95% credibility intervals around the primary outcome
through probabilistic sensitivity analysis (PSA) based on a Monte Carlo
simulation. We conducted one-way sensitivity analyses across key model parameters
and assessed the sensitivity of our results to the performance of the base case
separately through a scenario analysis. Finally, we assessed the sustainability
and feasibility of this program's scale up within the State's healthcare
financing structure through a budget impact analysis. The KSHI scenario results
in a health benefit to patients at a higher cost compared to the base case. The
mean ICER (US$46.4/disability-adjusted life year averted) is considered very cost
effective compared to a willingness-to-pay threshold of one gross domestic
product per capita (Nigeria, US$ 2012, 2,730). Our conclusion was robust to
uncertainty in parameters estimates (PSA: median US$49.1, 95% credible interval
21.9-152.3), during one-way sensitivity analyses, and when cost, quality, cost
and utilization parameters of the base case scenario were changed. The
sustainability of this program's scale up by the State is dependent on further
investments in healthcare. CONCLUSIONS: This study provides evidence that the
investment made by the KSHI program in rural Nigeria is likely to have been cost
effective; however, further healthcare investments are needed for this program to
be successfully expanded within Kwara State. Policy makers should consider
supporting financial initiatives to reduce maternal mortality tackling both
supply and demand issues in the access to care.
PMID- 26413789
TI - Evaluation of the long-term cost-effectiveness of liraglutide therapy for
patients with type 2 diabetes in France.
AB - OBJECTIVES: The present study aimed to compare the projected long-term clinical
and cost implications associated with liraglutide, sitagliptin and glimepiride in
patients with type 2 diabetes mellitus failing to achieve glycemic control on
metformin monotherapy in France. METHODS: Clinical input data for the modeling
analysis were taken from two randomized, controlled trials (LIRA-DPP4 and LEAD
2). Long-term (patient lifetime) projections of clinical outcomes and direct
costs (2013 Euros; ?) were made using a validated computer simulation model of
type 2 diabetes. Costs were taken from published France-specific sources. Future
costs and clinical benefits were discounted at 3% annually. Sensitivity analyses
were performed. RESULTS: Liraglutide was associated with an increase in quality
adjusted life expectancy of 0.25 quality-adjusted life years (QALYs) and an
increase in mean direct healthcare costs of ?2558 per patient compared with
sitagliptin. In the comparison with glimepiride, liraglutide was associated with
an increase in quality-adjusted life expectancy of 0.23 QALYs and an increase in
direct costs of ?4695. Based on these estimates, liraglutide was associated with
an incremental cost-effectiveness ratio (ICER) of ?10,275 per QALY gained vs
sitagliptin and ?20,709 per QALY gained vs glimepiride in France. CONCLUSION:
Calculated ICERs for both comparisons fell below the commonly quoted willingness
to-pay threshold of ?30,000 per QALY gained. Therefore, liraglutide is likely to
be cost-effective vs sitagliptin and glimepiride from a healthcare payer
perspective in France.
PMID- 26413790
TI - Erratum.
AB - JUDY OU, SEBASTIEN HAIART, STEVEN GALLUCCIO, JULIAN WHITE, and SCOTT A.
WEINSTEIN. (2015) An instructive case of presumed brown snake ( Pseudonaja spp.)
Envenoming Clinical Toxicology, 53(08), pp. 834-839.
http://dx.doi.org/10.3109/15563650.2015.1059947 When the above article was first
published online, there was an inadvertent omission from the authors' Conflict of
Interest statement. This unintentional omission is corrected below: The public
teaching hospital that employs two of the authors (JW and SAW) has a long
standing contract with CSL Ltd, the company that produces brown snake antivenom.
The hospital provides advice to health practitioners pertaining to the diagnosis
and management of envenoming and related toxinology diseases. The contract with
CSL Ltd allows such queries to CSL to be addressed through our hospital service.
Our department provides this service on behalf of the hospital. Dr. White
occasionally receives travel support to attend toxinology meetings from CSL Ltd.
However, neither he nor his family receives any financial remuneration or other
compensation from CSL Ltd. CSL Ltd had no role or input into this work.
PMID- 26413791
TI - Improvement of polypyrrole nanowire devices by plasmonic space charge generation:
high photocurrent and wide spectral response by Ag nanoparticle decoration.
AB - In this study, improvement of the opto-electronic properties of non-single
crystallized nanowire devices with space charges generated by localized surface
plasmon resonance (LSPR) is demonstrated. The photocurrent and spectral response
of single polypyrrole (PPy) nanowire (NW) devices are increased by
electrostatically attached Ag nanoparticles (Ag NPs). To take advantage of
plasmon-exciton coupling in the photocurrent of the device, 80 nm of Ag NPs (454
nm = lambdamax) were chosen for matching the maximum absorption with PPy NWs (442
nm = lambdamax). The photocurrent density is remarkably improved, up to 25.3
times (2530%), by the Ag NP decoration onto the PPy NW (PPyAgNPs NW) under blue
light (lambda = 425-475 nm) illumination. In addition, the PPyAgNPs NW shows a
photocurrent decay time twice that of PPy NW, as well as an improved spectral
response of the photocurrent. The improved photocurrent efficiency, decay time,
and spectral response resulted from the space charges generated by the LSPR of Ag
NPs. Furthermore, the increasing exponent (m) of the photocurrent (JPC ~ V(m))
and finite-differential time domain (FDTD) simulation straightforwardly indicate
relatively large plasmonic space charge generation under blue light illumination.
These results prove that the performance of non-single crystallized polymer
nanowire devices can also be improved by plasmonic enhancement.
PMID- 26413792
TI - Physicochemical and in vitro mucoadhesive properties of microparticles/discs of
betamethasone for the management of oral lichen planus.
AB - This study involved the preparation and evaluation of buccal-mucoadhesive
microparticles/discs of bethamethasone disodium phosphate (BDSP). The
microparticles were prepared using the emulsion solvent diffusion method.
Microparticles were prepared and characterized by encapsulation efficiency
particle size, Fourier Transform Infra Red (FTIR) spectrums, Differential
Scanning Calorimetric (DSC) thermograms and mucoadhesive properties. FTIR studies
reported that BDSP was changed to bethamethasone base molecule inside the intact
microparticles. The best drug to polymers ratio in microparticles was F1
containing 50 mg drug, 50 mg HPMC (as non-ionic and hydrophilic polymer) and 50
mg carbomer 934p (an anionic mucoadhesive polymer). The production yield of F1
microparticles was calculated as 78.60% with loading efficiency of about 65.14%
and the mean particle size was also measured as 281.84 MUm. It was proposed that
during the microparticle preparation procedure, water soluble salt of the drug
may be converted to the base which could be more effective in the buccal mucosa
due to its higher partition coefficient and lipophilicity. The highest and lowest
releases resulted from the discs prepared from F1 and F4, respectively, compared
with the commercial tablet and untreated drug powder (p < 0.05). The data
revealed that the discs exhibited good percentage of mucoadhesion (F1, 326
g/cm2). It may be concluded that drug loaded buccal-mucoadhesive microparticles
are a suitable delivery system for BDSP, and may be used in the effective
management of lichen planus.
PMID- 26413794
TI - Clinical outcome after switching therapy from ranibizumab and/or bevacizumab to
aflibercept in central retinal vein occlusion.
AB - PURPOSE: After 48 months, unresolved macular edema secondary to central retinal
vein occlusion (CRVO) is present in more than half of the patients treated with
ranibizumab/bevacizumab. Switching therapy to aflibercept, a more recent vascular
endothelial growth factor-A (VEGF-A) inhibitor, as well as VEGF-B and placental
growth factor inhibitor, might improve the clinical outcome in patients with CRVO
who respond insufficiently to ranibizumab/bevacizumab. METHODS: The presented
study is a retrospective analysis of CRVO patients (n = 13) responding
insufficiently to ranibizumab and/or bevacizumab (requiring treatment every 6
weeks or more frequently). Treatment in these patients was switched to
aflibercept, which was administered based on a 'treat and extend' regime. The
injection interval, relapse-free interval, central retinal thickness, central
retinal volume, visual acuity, and intraocular pressure (IOP) were evaluated
prior to switching to aflibercept and at month 6 and year 1 after switching
therapy. RESULTS: From baseline to year 1 after switching therapy to aflibercept,
the mean injection interval (primary end point) increased by 0.51 months (p =
0.023) and the relapse-free interval by 3.02 weeks (p = 0.003). The mean central
retinal thickness decreased by 195.84 um and the mean central retinal volume (6
mm diameter) by -1.81 mm3 (p = 0.007). Correspondingly, the mean ETDRS score
increased from 66.15 at baseline to 76.54 letters at year 1 after switching
therapy to aflibercept (+10.38 letters, p = 0.021). The IOP was not statistically
significantly affected (-1.2 mm Hg, p = 0.196). CONCLUSION: Switching therapy
from intravitreal ranibizumab/bevacizumab to aflibercept in insufficiently
responding macular edema secondary to CRVO elongates the injection interval and
the relapse-free interval and provides an improved anatomical as well as
functional outcome.
PMID- 26413795
TI - Recent patents and technology transfer for molecular diagnosis of beta
thalassemia and other hemoglobinopathies.
AB - INTRODUCTION: Biological tests and genetic analyses for diagnosis and
characterization of hematological diseases in health laboratories are designed
with the aim of meeting the major medical needs of hospitals and pharmaceutical
companies involved in this field of applied biomedicine. Genetic testing
approaches to perform diagnosis consist of molecular techniques, which should be
absolutely reproducible, fast, sensitive, cheap, and portable. AREAS COVERED:
Biological tests analyzed involve adult/newborn subjects, whereas genetic
analyses involve adult thalassemia patients, newborns, embryos/fetuses (including
non-invasive prenatal diagnosis), pre-implantation embryos, and pre-fertilization
oocytes. EXPERT OPINION: The most recent findings in the diagnostic approach for
beta-thalassemias are related to three major fields of investigation: moving
towards ultrasensitive methodologies for effective detection of the primary
causative mutation of beta-thalassemia, including the development of polymerase
chain reaction-free approaches and non-invasive prenatal diagnosis; comparing
analyses of the genotype of beta-thalassemia patients to high-HbF-associated
polymorphisms; introducing whole genome association assays and next-generation
sequencing. All these issues should be considered and discussed in the context of
several aspects, including regulatory, ethical and social issues. DNA sequence
data aligned with the identification of genes central to the induction,
development, progression, and outcome of beta-thalassemia will be a key point for
directing personalized therapy.
PMID- 26413793
TI - Ligament Tissue Engineering Using a Novel Porous Polycaprolactone Fumarate
Scaffold and Adipose Tissue-Derived Mesenchymal Stem Cells Grown in Platelet
Lysate.
AB - PURPOSE: Surgical reconstruction of intra-articular ligament injuries is hampered
by the poor regenerative potential of the tissue. We hypothesized that a novel
composite polymer "neoligament" seeded with progenitor cells and growth factors
would be effective in regenerating native ligamentous tissue. METHODS: We
synthesized a fumarate-derivative of polycaprolactone fumarate (PCLF) to create
macro-porous scaffolds to allow cell-cell communication and nutrient flow.
Clinical grade human adipose tissue-derived human mesenchymal stem cells (AMSCs)
were cultured in 5% human platelet lysate (PL) and seeded on scaffolds using a
dynamic bioreactor. Cell growth, viability, and differentiation were examined
using metabolic assays and immunostaining for ligament-related markers (e.g.,
glycosaminoglycans [GAGs], alkaline phosphatase [ALP], collagens, and tenascin
C). RESULTS: AMSCs seeded on three-dimensional (3D) PCLF scaffolds remain viable
for at least 2 weeks with proliferating cells filling the pores. AMSC
proliferation rates increased in PL compared to fetal bovine serum (FBS) (p <
0.05). Cells had a low baseline expression of ALP and GAG, but increased
expression of total collagen when induced by the ligament and tenogenic growth
factor fibroblast growth factor 2 (FGF-2), especially when cultured in the
presence of PL (p < 0.01) instead of FBS (p < 0.05). FGF-2 and PL also
significantly increased immunostaining of tenascin-C and collagen at 2 and 4
weeks compared with human fibroblasts. SUMMARY: Our results demonstrate that
AMSCs proliferate and eventually produce a collagen-rich extracellular matrix on
porous PCLF scaffolds. This novel scaffold has potential in stem cell engineering
and ligament regeneration.
PMID- 26413796
TI - Ultraviolet light-emitting-diode irradiation inhibits TNF-alpha and IFN-gamma
induced expression of ICAM-1 and STAT1 phosphorylation in human keratinocytes.
AB - BACKGROUND AND OBJECTIVES: Ultraviolet light-emitting diodes (UV-LEDs) are a
novel light source for phototherapy. This research investigated the in vitro
safety and efficacy of UV-LEDs as a phototherapeutic device for atopic dermatitis
(AD). STUDY DESIGN/MATERIALS AND METHODS: Human keratinocytes and fibroblasts
were irradiated by UV-LEDs with a center wavelength of 310 and 340 nm. We
examined the effects of UV-LED irradiation on the suppression of TNF-alpha/IFN
gamma-induced activation of STAT1 and ICAM-1 and on NF-kappaB expression; we used
the following methods: cell viability assay, reverse transcription-polymerase
chain reaction, enzyme-linked immunosorbent assay, Western blotting, and
immunocytochemistry. RESULTS: We observed anti-inflammatory responses through the
suppression of TNF-alpha/IFN-gamma-induced expression of TARC and MCP-1/CCL2, IL
1beta, IL-6, and sICAM-1 via blockage of ICAM-1 activation and subsequent
activation of STAT1 and NF-kappaB. The results suggested that UV-LED irradiation
inhibited ICAM expression by suppressing TNF-alpha/IFN-gamma-induced NF-kappaB
activation in vitro. CONCLUSION: We concluded that novel UV-LED (310 and 340 nm)
modalities were effective for the treatment of AD and may be promising for the
treatment of inflammatory skin diseases.
PMID- 26413797
TI - Berry Phenolic Compounds Increase Expression of Hepatocyte Nuclear Factor-1alpha
(HNF-1alpha) in Caco-2 and Normal Colon Cells Due to High Affinities with
Transcription and Dimerization Domains of HNF-1alpha.
AB - Hepatocyte nuclear factor-1alpha (HNF-1alpha) is found in the kidneys, spleen,
thymus, testis, skin, and throughout the digestive organs. It has been found to
promote the transcription of various proteins involved in the management of type
II diabetes, including dipeptidyl peptidase-IV (DPP-IV). Phenolic compounds from
berries and citrus fruits are known to inhibit DPP-IV, but have not been tested
for their interactions with wild-type HNF-1alpha. By studying the interactions of
compounds from berries and citrus fruits have with HNF-1alpha, pre
transcriptional mechanisms that inhibit the expression of proteins such as DPP-IV
may be elucidated. In this study, the interactions of berry phenolic compounds
and citrus flavonoids with the dimerization and transcriptional domains of HNF
1alpha were characterized using the molecular docking program AutoDock Vina. The
anthocyanin delphinidin-3-O-arabinoside had the highest binding affinity for the
dimerization domain as a homodimer (-7.2 kcal/mol) and transcription domain (-8.3
kcal/mol) of HNF-1alpha. Anthocyanins and anthocyanidins had relatively higher
affinities than resveratrol and citrus flavonoids for both, the transcription
domain and the dimerization domain as a homodimer. The flavonoid flavone had the
highest affinity for a single unit of the dimerization domain (-6.5 kcal/mol).
Nuclear expression of HNF-1alpha was measured in Caco-2 and human normal colon
cells treated with blueberry and blackberry anthocyanin extracts. All extracts
tested increased significantly (P < 0.05) the nuclear expression of HNF-1alpha in
Caco-2 cells by 85.2 to 260% compared to a control. The extracts tested increased
significantly (P < 0.02) the nuclear expression of HNF-1alpha in normal colon
cells by 48.6 to 243%. It was confirmed that delphinidin-3-O-glucoside increased
by 3-fold nuclear HNF-1alpha expression in Caco-2 cells (P < 0.05). Anthocyanins
significantly increased nuclear HNF-1alpha expression, suggesting that these
compounds might regulate the genes HNF-1alpha promotes.
PMID- 26413798
TI - Correction: CD26 Expression on T Helper Populations and sCD26 Serum Levels in
Patients with Rheumatoid Arthritis.
PMID- 26413799
TI - Drug-Drug Molecular Salt Hydrate of an Anticancer Drug Gefitinib and a Loop
Diuretic Drug Furosemide: An Alternative for Multidrug Treatment.
AB - A 1:1 monohydrate salt containing gefitinib, an orally administrated chemotherapy
treatment for lung and breast cancers and furosemide, a loop diuretic drug,
commonly used in the treatment of hypertension and edema, has been prepared. The
molecular salt crystallized in triclinic P-1 space group. The C-O bond lengths
(~1.26 A) in the COOH group show that proton transfer has occurred from
furosemide to morpholine moiety of the gefitinib suggesting cocrystal to be
ionic. The morpholine moiety of the gefitinib showed significant conformational
change because of its involvement in conformation dictating the strong N-H...O
hydrogen bonding interaction. The strong hydrogen bonding interaction between
gefitinib and furosemide places their benzene rings in stacking mode to
facilitate the generation of pi-stack dimers. The neighboring dimers are bridged
to each other via water molecule through N-H...O, C-H...O, O-H...N, and O-H...O
interactions. The remarkable stability of the salt hydrate could be attributed to
the strong hydrogen bonding interactions in the crystal structure. Interestingly,
release of water from the lattice at 140 degrees C produced new anhydrous salt
that has better solubility and dissolution rate than salt hydrate. The drug-drug
molecular salt may have some bearing on the treatment of patient suffering from
anticancer and hypertension.
PMID- 26413800
TI - Eco-efficiency of agricultural water systems: Methodological approach and
assessment at meso-level scale.
AB - This study presents a methodological framework for the meso-level eco-efficiency
assessment of agricultural water systems using a life-cycle system-based
approach. The methodology was applied to the Sinistra Ofanto irrigation scheme,
located in Southern Italy, where about 28,165 ha are under irrigation. The
environmental performance of the system was evaluated through a set of selected
mid-point environmental impact categories while the economic performance was
measured using the total value added to the system's final products due to water
use and the adopted management practices. Both economic performance and
environmental performance were measured at different stages and for each
stakeholder in the value chain. A distinction was made between foreground and
background systems referring, respectively, to the processes that occurred inside
the water system boundaries and those used for the production of supplementary
resources. The analysis revealed that the major environmental burdens are: i) the
freshwater resource depletion (i.e. excessive groundwater pumping), ii) climate
change (i.e. direct emissions due to fertilizer use and diesel combustion), and
iii) eutrophication (as a result of excessive application of N and P
fertilizers). A considerable impact was observed on the background system where
energy, fuel and agrochemicals were produced thereby confirming the prominent
role of background processes in the comprehensive eco-efficiency assessment. The
presented methodology aimed at the quantitative assessment of the eco-efficiency
level rather than at the identification of the most affected environmental
category. Hence, the results can be used to compare the performance of the system
from one year to the next, among different stakeholders (water users) and/or to
assess the impact of adopting innovative technologies and management practices.
Moreover, the presented approach is useful for comparing the performance among
different agricultural water systems and also in respect to other meso-level
water systems in a cross-sectorial analysis.
PMID- 26413801
TI - Residues of endosulfan in surface and subsurface agricultural soil and its
bioremediation.
AB - The persistence of many hydrophobic pesticides has been reported by various
workers in various soil environments and its bioremediation is a major concern
due to less bioavailability. In the present study, the pesticide residues in the
surface and subsurface soil in an area of intense agricultural activity in Pakkam
Village of Thiruvallur District, Tamilnadu, India, and its bioremediation using a
novel bacterial consortium was investigated. Surface (0-15 cm) and subsurface
soils (15-30 cm and 30-40 cm) were sampled, and pesticides in different layers of
the soil were analyzed. Alpha endosulfan and beta endosulfan concentrations
ranged from 1.42 to 3.4 mg/g and 1.28-3.1 mg/g in the surface soil, 0.6-1.4 mg/g
and 0.3-0.6 mg/g in the subsurface soil (15-30 cm), and 0.9-1.5 mg/g and 0.34-1.3
mg/g in the subsurface soil (30-40 cm) respectively. Residues of other persistent
pesticides were also detected in minor concentrations. These soil layers were
subjected to bioremediation using a novel bacterial consortium under a simulated
soil profile condition in a soil reactor. The complete removal of alpha and beta
endosulfan was observed over 25 days. Residues of endosulfate were also detected
during bioremediation, which was subsequently degraded on the 30th day. This
study revealed the existence of endosulfan in the surface and subsurface soils
and also proved that the removal of such a ubiquitous pesticide in the surface
and subsurface environment can be achieved in the field by bioaugumenting a
biosurfactant-producing bacterial consortium that degrades pesticides.
PMID- 26413802
TI - Temporal trends of perfluoroalkyl substances in limed biosolids from a large
municipal water resource recovery facility.
AB - While the recycling of wastewater biosolids via land-application is a sustainable
practice for nutrient recovery and soil reclamation that has become increasingly
common worldwide, concerns remain that this practice may become a source of
toxic, persistent organic pollutants to the environment. This study concentrates
on assessing the presence and the temporal trends of 12 perfluoroalkyl substances
(PFASs), pollutants of global consequence, in limed Class B biosolids from a
municipal water resource recovery facility (WRRF), also know as a wastewater
treatment plant. PFASs are of significant concern due to their extensive presence
and persistence in environmental and biotic samples worldwide, most notably human
blood samples. Class B biosolids were collected from the WRRF, prior to land
application, approximately every two to three months, from 2005 to 2013. Overall,
this study found that concentrations of the 7 detectable PFAS compounds remained
unchanged over the 8-year period, a result that is consistent with other temporal
studies of these compounds in sewage sludges. From these analyzed compounds, the
highest mean concentrations observed over the study period were 25.1 ng/g dw,
23.5 ng/g dw, and 22.5 ng/g dw for perfluorononanoic acid (PFNA),
perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS),
respectively, and these compounds were detected at concentrations 2.5-5 times
higher than the remaining, detectable PFASs. Furthermore, it was observed that
PFOS, while demonstrating no overall change during the study, exhibited a visible
spike in concentration from late 2006 to early 2007. This study indicates that
concentrations of PFASs in WRRFs have been stagnant over time, despite
regulation. This study also demonstrates that the use of glass jars with
polytetrafluoroethylene-lined lids, a common storage method for environmental
samples, will not influence PFOA and PFNA concentrations in archived biosolids
samples.
PMID- 26413803
TI - Degradation of enoxacin antibiotic by the electro-Fenton process: Optimization,
biodegradability improvement and degradation mechanism.
AB - This study aims to investigate the effectiveness of the electro-Fenton process on
the removal of a second generation of fluoroquinolone, enoxacin. The
electrochemical reactor involved a carbon-felt cathode and a platinum anode. The
influence of some experimental parameters, namely the initial enoxacin
concentration, the applied current intensity and the Fe(II) amount, was examined.
The degradation of the target molecule was accompanied by an increase of the
biodegradability, assessed from the BOD5 on COD ratio, which increased from 0
before treatment until 0.5 after 180 min of electrolysis at 50 mg L(-1) initial
enoxacin concentration, 0.2 mmol L(-1) Fe(II) concentration and 300 mA applied
current intensity. TOC and COD time-courses were also evaluated during
electrolysis and reached maximum residual yields of 54% and 43% after 120 min of
treatment, respectively. Moreover, a simultaneous generation of inorganic ions
(fluorides, ammonium and nitrates) were observed and 3 short chain carboxylic
acids (formic, acetic and oxalic acids) were identified and monitored during 180
min of electrolysis. By-products were identified according to UPLC-MS/MS results
and a degradation pathway was proposed.
PMID- 26413804
TI - The potential for tree planting strategies to reduce local and regional ecosystem
impacts of agricultural ammonia emissions.
AB - Trees are very effective at capturing both gaseous and particulate pollutants
from the atmosphere. But while studies have often focussed on PM and NOx in the
urban environment, little research has been carried out on the tree effect of
capturing gaseous emissions of ammonia in the rural landscape. To examine the
removal or scavenging of ammonia by trees a long-range atmospheric model (FRAME)
was used to compare two strategies that could be used in emission reduction
policies anywhere in the world where nitrogen pollution from agriculture is a
problem. One strategy was to reduce the emission source strength of livestock
management systems by implementing two 'tree-capture' systems scenarios - tree
belts downwind of housing and managing livestock under trees. This emission
reduction can be described as an 'on-farm' emission reduction policy, as ammonia
is 'stopped' from dispersion outside the farm boundaries. The second strategy was
to apply an afforestation policy targeting areas of high ammonia emission through
two planting scenarios of increasing afforestation by 25% and 50%. Both
strategies use trees with the aim of intercepting NH3 emissions to protect semi
natural areas. Scenarios for on-farm emission reductions showed national
reductions in nitrogen deposition to semi-natural areas of 0.14% (0.2 kt N-NHx)
to 2.2% (3.15 kt N-NHx). Scenarios mitigating emissions from cattle and pig
housing gave the highest reductions. The afforestation strategy showed national
reductions of 6% (8.4 kt N-NHx) to 11% (15.7 kt N-NHx) for 25% and 50%
afforestation scenarios respectively. Increased capture by the planted trees also
showed an added benefit of reducing long range effects including a decrease in
wet deposition up to 3.7 kt N-NHx (4.6%) and a decrease in export from the UK up
to 8.3 kt N-NHx (6.8%).
PMID- 26413805
TI - Simultaneous biosorption of selenium, arsenic and molybdenum with modified algal
based biochars.
AB - Ash disposal waters from coal-fired power stations present a challenging water
treatment scenario as they contain high concentrations of the oxyanions Se, As
and Mo which are difficult to remove through conventional techniques. In an
innovative process, macroalgae can be treated with Fe and processed through slow
pyrolysis into Fe-biochar which has a high affinity for oxyanions. However, the
effect of production conditions on the efficacy of Fe-biochar is poorly
understood. We produced Fe-biochar from two algal sources; "Gracilaria waste"
(organic remnants after agar is extracted from cultivated Gracilaria) and the
freshwater macroalgae Oedogonium. Pyrolysis experiments tested the effects of the
concentration of Fe(3+) in pre-treatment, and pyrolysis temperatures, on the
efficacy of the Fe-biochar. The efficacy of Fe-biochar increased with increasing
concentrations of Fe(3+) in the pre-treatment solutions, and decreased with
increasing pyrolysis temperatures. The optimized Fe-biochar for each biomass was
produced by treatment with a 12.5% w/v Fe(3+) solution, followed by slow
pyrolysis at 300 degrees C. The Fe-biochar produced in this way had higher a
biosorption capacity for As and Mo (62.5-80.7 and 67.4-78.5 mg g(-1)
respectively) than Se (14.9-38.8 mg g(-1)) in single-element mock effluents, and
the Fe-biochar produced from Oedogonium had a higher capacity for all elements
than the Fe-biochar produced from Gracilaria waste. Regardless, the optimal Fe
biochars from both biomass sources were able to effectively treat Se, As and Mo
simultaneously in an ash disposal effluent from a power station. The production
of Fe-biochar from macroalgae is a promising technique for treatment of complex
effluents containing oxyanions.
PMID- 26413806
TI - Spatial Patterns and Risk Assessment of Heavy Metals in Soils in a Resource
Exhausted City, Northeast China.
AB - Northeast China is an intensive area of resource-exhausted city, which is facing
the challenges of industry conversion and sustainable development. In order to
evaluate the soil environmental quality influenced by mining activities over
decades, the concentration and spatial distribution of arsenic (As), cadmium
(Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), and Zinc (Zn) in
surface soils (0-20cm) of a typical resource-exhausted city were investigated by
analyzing 306 soil samples. The results showed that the average concentrations in
the samples were 6.17 mg/kg for As, 0.19 mg/kg for Cd, 51.08 mg/kg for Cr, 23.27
mg/kg for Cu, 31.15 mg/kg for Ni, 22.17 mg/kg for Pb, and 54.21 mg/kg for Zn.
Metals distribution maps produced by using the inverse distance weighted
interpolation method and results revealed that all investigated metals showed
distinct geographical patterns, and the concentrations were higher in urban and
industrial areas than in farmland. Pearson correlation and principal component
analysis showed that there were significant positive correlations (p<0.05)
between all of the metals, and As, Cd, Cr, Mn, Ni, Pb, and Zn were closely
associated with the first principal component (PC1), which explained 39.81% of
the total variance. Cu and As were mainly associated with the second component
(PC2). Based on the calculated Nemerow pollution index, percentage for slightly
polluted (1
90%. Employing small molecule- and decoy-peptide-based
approaches we further affirm that complete remission of BCCs could only be
achieved by combined inhibition of p50-NFkappaB/Bcl3 and Shh signaling. We posit
that Ptch1+/-/SKH-1 mice are a novel and relevant animal model for NBCCS.
Understanding mechanisms that govern genetic predisposition to BCCs should
facilitate our ability to identify and treat NBCCS gene carriers, including those
at risk for sporadic BCCs while accelerating development of novel therapeutic
modalities for these patients.
PMID- 26413812
TI - JAK2 tyrosine kinase mediates integrin activation induced by CXCL12 in B-cell
chronic lymphocytic leukemia.
AB - Chemokines participate to B-cell chronic lymphocytic leukemia (B-CLL)
pathogenesis by promoting cell adhesion and survival in bone marrow stromal
niches and mediating cell dissemination to secondary lymphoid organs. In this
study we investigated the role of JAK protein tyrosine kinases (PTK) in adhesion
triggering by the CXC chemokine CXCL12 in normal versus CLL B-lymphocytes. We
demonstrate that CXCL12 activates JAK2 in normal as well as CLL B-lymphocytes,
with kinetics consistent with rapid adhesion triggering. By using complementary
methodologies of signal transduction interference, we found that JAK2 mediates
CXCL12-triggered activation of lymphocyte function-associated antigen-1 (LFA-1)
and very late antigen-4 (VLA-4) integrins. We also show that JAK2 mediates the
activation of the small GTP-binding protein RhoA, in turn controlling LFA-1
affinity triggering by CXCL12. Importantly, comparative analysis of 41 B-CLL
patients did not evidence JAK2 functional variability between subjects, thus
suggesting that JAK2, differently from other signaling events involved in
adhesion regulation in B-CLL, is a signaling molecule downstream to CXCR4
characterized by a conserved regulatory role. Our results reveal JAK2 as critical
component of chemokine signaling in CLL B-lymphocytes and indicate JAK inhibition
as a potentially useful new pharmacological approach to B-CLL treatment.
PMID- 26413813
TI - GLI1 orchestrates CXCR4/CXCR7 signaling to enhance migration and metastasis of
breast cancer cells.
AB - The up-regulation of chemokine receptors CXCR4 and CXCR7 impacts on the distant
metastasis and prognosis of breast cancer, though knowledge about the regulatory
mechanism of their expressions is limited. Meanwhile, the GLI transcription
factors of Hedgehog signaling have been reported to play a pivotal role in the
development and progression of many types of human cancer. In breast cancer, the
increased expression of GLI1 correlated with metastasis and unfavorable overall
prognosis, though its molecular mechanism is also not fully understood. Based on
our findings that GLI1 enhanced the lung metastasis of breast cancer cells in a
mouse model system, we comprehensively screened for genes up-regulated by GLI1 in
breast cancer cells, and as such identified CXCR4, CXCR7/ACKR3, and actin-binding
protein LCP1/L-PLASTIN, all of which have been reported to be involved in CXCL12
stimulating signaling. In breast cancer cells, we found that GLI1 and GLI2 up
regulated these expressions, while treatment with GLI-specific inhibitor GANT61
reduced the expressions. As for CXCR4, we confirmed it as a direct target of GLI1
through the reporter assay and the chromatin immunoprecipitation assay. We also
found that GLI1 enhanced CXCL12-induced ERK phosphorylation and cell migration,
both of which were blocked by either CXCR4-specific inhibitor or knockdown of
CXCR7 or LCP1. These evidences suggest an indispensable role of GLI1 in the
migration and metastasis of breast cancer cells through CXCL12/CXCR4 signaling
enhancement.
PMID- 26413814
TI - Valproic acid enhances the efficacy of radiation therapy by protecting normal
hippocampal neurons and sensitizing malignant glioblastoma cells.
AB - Neurocognitive deficits are serious sequelae that follow cranial irradiation used
to treat patients with medulloblastoma and other brain neoplasms. Cranial
irradiation causes apoptosis in the subgranular zone of the hippocampus leading
to cognitive deficits. Valproic acid (VPA) treatment protected hippocampal
neurons from radiation-induced damage in both cell culture and animal models.
Radioprotection was observed in VPA-treated neuronal cells compared to cells
treated with radiation alone. This protection is specific to normal neuronal
cells and did not extend to cancer cells. In fact, VPA acted as a radiosensitizer
in brain cancer cells. VPA treatment induced cell cycle arrest in cancer cells
but not in normal neuronal cells. The level of anti-apoptotic protein Bcl-2 was
increased and the pro-apoptotic protein Bax was reduced in VPA treated normal
cells. VPA inhibited the activities of histone deacetylase (HDAC) and glycogen
synthase kinase-3beta (GSK3beta), the latter of which is only inhibited in normal
cells. The combination of VPA and radiation was most effective in inhibiting
tumor growth in heterotopic brain tumor models. An intracranial orthotopic glioma
tumor model was used to evaluate tumor growth by using dynamic contrast-enhanced
magnetic resonance (DCE MRI) and mouse survival following treatment with VPA and
radiation. VPA, in combination with radiation, significantly delayed tumor growth
and improved mouse survival. Overall, VPA protects normal hippocampal neurons and
not cancer cells from radiation-induced cytotoxicity both in vitro and in vivo.
VPA treatment has the potential for attenuating neurocognitive deficits
associated with cranial irradiation while enhancing the efficiency of glioma
radiotherapy.
PMID- 26413815
TI - Differential expression and biochemical activity of the immune receptor Tim-3 in
healthy and malignant human myeloid cells.
AB - The T cell immunoglobulin and mucin domain 3 (Tim-3) is a plasma membrane
associated receptor which is involved in a variety of biological responses in
human immune cells. It is highly expressed in most acute myeloid leukaemia (AML)
cells and therefore may serve as a possible target for AML therapy. However, its
biochemical activities in primary human AML cells remain unclear. We therefore
analysed the total expression and surface presence of the Tim-3 receptor in
primary human AML blasts and healthy primary human leukocytes isolated from human
blood. We found that Tim-3 expression was significantly higher in primary AML
cells compared to primary healthy leukocytes. Tim-3 receptor molecules were
distributed largely on the surface of primary AML cells, whereas in healthy
leukocytes Tim-3 protein was mainly expressed intracellularly. In primary human
AML blasts, both Tim-3 agonistic antibody and galectin-9 (a Tim-3 natural ligand)
significantly upregulated mTOR pathway activity. This was in line with increased
accumulation of hypoxia-inducible factor 1 alpha (HIF-1alpha) and secretion of
VEGF and TNF-alpha. Similar results were obtained in primary human healthy
leukocytes. Importantly, in both types of primary cells, Tim-3-mediated effects
were compared with those induced by lipopolysaccharide (LPS) and stem cell factor
(SCF). Tim-3 induced comparatively moderate responses in both AML cells and
healthy leukocytes. However, Tim-3, like LPS, mediated the release of both TNF
alpha and VEGF, while SCF induced mostly VEGF secretion and did not upregulate
TNF-alpha release.
PMID- 26413817
TI - Relationship between self-focused attention, mindfulness and distress in
individuals with auditory verbal hallucinations.
AB - INTRODUCTION: The purpose of this study was to investigate the relationships
among self-focused attention, mindfulness and distress caused by the voices in
psychiatric patients. METHODS: Fifty-one individuals with a psychiatric diagnosis
participated in this study. The Psychotic Symptom Rating Scale (PSYRATS)
emotional factor was applied to measure the distress caused by the voices, the
Self-Absorption Scale (SAS) was given for measuring the levels of self-focused
attention, and the Mindful Attention Awareness Scale (MAAS) was used to measure
mindfulness. RESULTS: The results showed that distress caused by the voices
correlated positively with self-focused attention (private and public) and
negatively with mindfulness. A negative correlation was also found between
mindfulness and self-focused attention (private and public). Finally, multiple
linear regression analysis showed that public self-focus was the only factor
predicting distress caused by the voices. CONCLUSIONS: Intervention directed at
diminishing public self-focused attention and increasing mindfulness could
improve distress caused by the voices.
PMID- 26413821
TI - Temporospatial and kinetic gait variables of Doberman Pinschers with and without
cervical spondylomyelopathy.
AB - OBJECTIVE: To characterize and compare gait variables in Doberman Pinschers with
and without cervical spondylomyelopathy (CSM). ANIMALS: 18 Doberman Pinschers (9
clinically normal dogs and 9 CSM-affected dogs). PROCEDURES: A neurologic
examination was performed on all dogs. The diagnosis of CSM was confirmed with
MRI. Temporospatial and kinetic gait variables were measured by use of a pressure
sensitive walkway. Temporospatial variables evaluated included stance phase
duration, swing phase duration, gait cycle duration, stride length, and gait
velocity. Kinetic variables evaluated included peak vertical force and vertical
impulse. Random-effects linear regression was used to determine the difference
between CSM-affected and clinically normal dogs for each of the 7 variables.
RESULTS: Values for temporospatial variables were significantly smaller in the
thoracic limbs of CSM-affected dogs, compared with values for the thoracic limbs
of clinically normal dogs. For the kinetic variables, peak vertical force was
significantly higher in the thoracic limbs than the pelvic limbs for all dogs.
Vertical impulse values were higher in the thoracic limbs than the pelvic limbs.
There were significant differences in mean vertical impulse between the thoracic
and pelvic limbs for both groups. CONCLUSIONS AND CLINICAL RELEVANCE: In this
study, significant differences in temporospatial variables were identified
between the thoracic limbs of clinically normal and CSM-affected dogs, with the
values being smaller for the CSM-affected dogs than for the clinically normal
dogs. A pressure-sensitive walkway may provide a valid, practical option for
rapid, objective assessment of gait and response to treatment in dogs with CSM.
PMID- 26413816
TI - Chlamydia trachomatis immunoglobulin G3 seropositivity is a predictor of
reproductive outcomes in infertile women with patent fallopian tubes.
AB - OBJECTIVE: To determine if Chlamydia trachomatis (C. trachomatis) seropositivity,
as detected by the C. trachomatis elementary body (EB)-based enzyme-linked
immunosorbent assay [EB ELISA] predicts pregnancy and pregnancy outcome among
infertile women with documented tubal patency. DESIGN: Cohort study. SETTING:
Outpatient clinics. PATIENT(S): In all, 1,250 infertile women with documented
tubal patency enrolled in 1 of 2 randomized controlled trials: Pregnancy in
Polycystic Ovary Syndrome II; and the Assessment of Multiple Intrauterine
Gestations From Ovarian Stimulation. INTERVENTION(S): Sera were analyzed for anti
C. trachomatis immunoglobulin G (IgG)1 and IgG3 antibodies, using a research C.
trachomatis EB ELISA. The optical density (OD)405 readings of >= 0.35 and >= 0.1
were considered positive for IgG1 and IgG3, respectively. MAIN OUTCOME
MEASURE(S): Primary outcomes included pregnancy, live birth, and ectopic
pregnancy. Log-linear regression was used to determine the relative risk after
adjusting for age, race, treatment medication, smoking status, and current
alcohol use. RESULT(S): A total of 243 (19%) women were seropositive for anti-C.
trachomatis IgG3. They tended to be nonwhite and smokers. Anti-C. trachomatis
IgG3 seropositive women were significantly less likely to conceive (risk ratio
[RR] 0.65, 95% confidence interval [CI] 0.52-0.83) or to have a live birth (RR
0.59, 95% CI 0.43-0.80); these associations were weakened after adjusting for
number of hysterosalpingography-documented patent tubes (RR 0.73, 95% CI 0.56
0.97) and (RR 0.73, 95% CI 0.50-1.04), respectively. Anti-C. trachomatis IgG3
seropositive women who conceived had a *2.7 risk (95% CI 1.40-5.34) of ectopic
pregnancy. CONCLUSION(S): Even in the presence of tubal patency, anti-C.
trachomatis IgG3 seropositivity is associated with a lower likelihood of
pregnancy. Anti-C. trachomatis IgG3 seropositive women have as high as 3 times
the risk of ectopic pregnancy. CLINICAL TRIAL REGISTRATION NUMBER: PPCOSII:
NCT00719186 and AMIGOS: NCT01044862.
PMID- 26413818
TI - DNA Methylation Dynamics During Differentiation, Proliferation, and Tumorigenesis
in the Intestinal Tract.
AB - DNA methylation, an epigenetic control mechanism in mammals, is widely present in
the intestinal tract during the differentiation and proliferation of epithelial
cells. Cells in stem cell pools or villi have different patterns of DNA
methylation. The process of DNA methylation is dynamic and occurs at many
relevant regulatory elements during the rapid transition of stem cells into fully
mature, differentiated epithelial cells. Changes in DNA methylation patterns most
often take place in enhancer and promoter regions and are associated with
transcription factor binding. During differentiation, enhancer regions associated
with genes important to enterocyte differentiation are demethylated, activating
gene expression. Abnormal patterns of DNA methylation during differentiation and
proliferation in the intestinal tract can lead to the formation of aberrant crypt
foci and destroy the barrier and absorptive functions of the intestinal
epithelium. Accumulation of these epigenetic changes may even result in
tumorigenesis. In the current review, we discuss recent findings on the
association between DNA methylation and cell differentiation and proliferation in
the small intestine and highlight the possible links between dysregulation of
this process and tumorigenesis.
PMID- 26413822
TI - Evaluation of the safety of long-term, daily oral administration of grapiprant, a
novel drug for treatment of osteoarthritic pain and inflammation, in healthy
dogs.
AB - OBJECTIVE: To investigate the safety of daily oral administration of grapiprant
to dogs. ANIMALS: Thirty-six 9-month-old Beagles of both sexes. PROCEDURES: Dogs
were randomly assigned to groups that received grapiprant via oral gavage at 0,
1, 6, or 50 mg/kg (total volume, 5 mL/kg), q 24 h for 9 months. Each group
contained 4 dogs of each sex (ie, 8 dogs/group), except for the 50 mg/kg group,
which included 4 additional dogs that were monitored for an additional 30 days
after treatment concluded (recovery period). All dogs received ophthalmologic,
ECG, and laboratory evaluations before treatment began (baseline) and
periodically afterward. All dogs were observed daily. Dogs were euthanized at the
end of the study for necropsy and histologic evaluation. RESULTS: All dogs
remained clinically normal during treatment, with no apparent changes in appetite
or demeanor. Emesis and soft or mucoid feces that occasionally contained blood
were observed in all groups, although these findings were more common in dogs
that received grapiprant. In general, clinicopathologic findings remained within
baseline ranges. Drug-related changes in serum total protein and albumin
concentrations were detected, but differences were small and resolved during
recovery. No drug-related gross or microscopic pathological changes were detected
in tissue samples except mild mucosal regeneration in the ileum of 1 dog in the
50 mg/kg group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested the safety
of long-term oral administration of grapiprant to dogs. Efficacy of grapiprant in
the treatment of dogs with osteoarthritis needs to be evaluated in other studies.
PMID- 26413823
TI - Bactericidal effects of various concentrations of enrofloxacin, florfenicol,
tilmicosin phosphate, and tulathromycin on clinical isolates of Mannheimia
haemolytica.
AB - OBJECTIVE: To determine bactericidal effects of enrofloxacin, florfenicol,
tilmicosin, and tulathromycin on clinical isolates of Mannheimia haemolytica at
various bacterial densities and drug concentrations. SAMPLE: 4 unique isolates of
M haemolytica recovered from clinically infected cattle. PROCEDURES: Minimum
inhibitory concentration (MIC) and mutant prevention concentration (MPC) were
determined for each drug and isolate. Mannheimia haemolytica suspensions (10(6)
to 10(9) CFUs/mL) were exposed to the determined MIC and MPC and preestablished
maximum serum and tissue concentrations of each drug. Log10 reduction in viable
cells (percentage of cells killed) was measured at various points. RESULTS:
Bacterial killing at the MIC was slow and incomplete. After 2 hours of isolate
exposure to the MPC and maximum serum and tissue concentrations of the tested
drugs, 91% to almost 100% cell killing was achieved with enrofloxacin, compared
with 8% growth to 93% cell killing with florfenicol, 199% growth to 63% cell
killing with tilmicosin, and 128% growth to 43% cell killing with tulathromycin
over the range of inoculum tested. For all drugs, killing of viable organisms was
evident at all bacterial densities tested; however, killing was more substantial
at the MPC and maximum serum and tissue drug concentrations than at the MIC and
increased with duration of drug exposure. Rank order of drugs by killing potency
was enrofloxacin, florfenicol, tilmicosin, and tulathromycin. CONCLUSIONS AND
CLINICAL RELEVANCE: Findings suggested that antimicrobial doses that equaled or
exceeded the MPC provided rapid killing of M haemolytica by the tested drugs,
decreasing opportunities for antimicrobial-resistant subpopulations of bacteria
to develop during drug exposure.
PMID- 26413824
TI - Development of a model to induce transient synovitis and lameness in the hip
joint of dogs.
AB - OBJECTIVE: To develop a model of hip joint synovitis on the basis of intra
articular injection of a sodium urate suspension in dogs and to characterize
associated gait changes. ANIMALS: 6 healthy adult dogs. PROCEDURES: Each dog was
sedated, and synovitis was induced by injection of 1 mL of a sodium urate
suspension (20 mg/mL) into the right hip joint under ultrasonographic guidance.
Observational and instrumented gait analyses to determine temporospatial,
kinetic, and kinematic variables were performed prior to and 4, 8, and 24 hours
after sedation and synovitis induction. RESULTS: Injection of a sodium urate
suspension into the hip joint of healthy dogs resulted in lameness of the
ipsilateral pelvic limb as determined by observational and instrumented gait
analyses. For all dogs, lameness was clinically detectable within 1.5 to 2 hours
after injection, reached its maximum intensity at 4 hours after injection, and
had subsided by 24 hours after injection. CONCLUSIONS AND CLINICAL RELEVANCE:
Results indicated that injection of a sodium urate suspension into the hip joint
of healthy dogs reliably induced synovitis and signs of pain and lameness in the
ipsilateral pelvic limb that lasted 24 hours. This model can be used in
conjunction with instrumented gait analysis to provide information on gait
changes associated with hip joint disease and might be useful for evaluating the
efficacy of analgesics or other interventions for the treatment of hip joint
disease in dogs.
PMID- 26413825
TI - In vitro assessment of bacterial translocation during needle insertion through
inoculated culture media as a model of arthrocentesis through cellulitic tissue.
AB - OBJECTIVE: To determine by use of an in vitro model the potential for
translocating sufficient numbers of bacteria into a joint during arthrocentesis
through cellulitic tissue to cause sepsis. SAMPLE: Culture media containing 4
concentrations of Staphylococcus aureus and needles of 3 sizes. PROCEDURES:
Needles (22, 20, and 19 gauge) were inserted through Mueller-Hinton agar that
contained known concentrations of S aureus (10(3),10(4),10(5), and 10(6)
CFUs/mL). After a needle exited through the medium, any agar plug within the
needle bore was ejected into a sterile syringe and the contaminated portion of
the needle was harvested. Sterile saline (0.9% NaCl) solution was used to
emulsify the agar plug and wash the contaminated portion of the needle. The
resulting solution was cultured to determine the number of bacterial CFUs that
could be deposited into a joint during arthrocentesis through contaminated
tissue. RESULTS: Needle gauge and bacterial concentration were both associated
with the number of bacterial CFUs deposited after insertion through contaminated
agar. Although all needle sizes were capable of bacterial translocation
sufficient to cause septic arthritis, ORs for 20- and 22-gauge needles
translocating > 33 CFUs of S aureus were significantly higher than the OR for a
19-gauge needle. The ORs for 20- or 22-gauge needles translocating > 33 CFUs of S
aureus (the minimum population of S aureus known to cause joint sepsis) were
0.22. CONCLUSIONS AND CLINICAL RELEVANCE: Results for this in vitro model
indicated that caution should be used when performing arthrocentesis through
cellulitic tissue.
PMID- 26413826
TI - Evaluation of serum amyloid A and haptoglobin concentrations as prognostic
indicators for horses with inflammatory disease examined at a tertiary care
hospital.
AB - OBJECTIVE: To evaluate use of serum amyloid A (SAA) and haptoglobin
concentrations as prognostic indicators for horses with inflammatory disease in
regard to euthanasia, complications, and hospitalization duration and cost.
ANIMALS: 20 clinically normal horses and 53 horses with inflammatory disease.
PROCEDURES: Total WBC count, neutrophil count, and fibrinogen, SAA, and
haptoglobin concentrations were determined for clinically normal horses and
horses with suspected inflammatory disease. Clinicopathologic values at admission
were compared to test the use of SAA and haptoglobin concentrations in predicting
euthanasia, complications, and hospitalization duration and cost. Haptoglobin and
SAA concentrations of 22 horses were monitored during hospitalization to test the
use of serial measurements in predicting survival and complications. RESULTS:
Neutrophil count and SAA and haptoglobin concentrations were significantly
different at admission for horses with inflammatory disease, compared with those
for clinically normal horses. Horses with colitis and peritonitis had
significantly higher SAA and haptoglobin concentrations than clinically normal
horses. A moderate positive correlation (r = 0.355) between hospitalization
duration and haptoglobin concentration was identified. Horses with an increase in
SAA concentration between 24 and 72 hours after admission, compared with
admission SAA concentration, were significantly more likely (OR, 7.0; 95%
confidence interval, 1.1 to 45.9) to be euthanized or develop complications.
CONCLUSIONS AND CLINICAL RELEVANCE: Concentrations of SAA and haptoglobin at
admission were not significantly correlated with outcome in horses with
inflammatory conditions. Acute-phase proteins likely have more utility in serial
analysis rather than testing at a single time point for horses with inflammatory
conditions.
PMID- 26413827
TI - Effects of a docosahexaenoic acid-rich microalgae nutritional product on insulin
sensitivity after prolonged dexamethasone treatment in healthy mature horses.
AB - OBJECTIVE: To determine effects of a microalgae nutritional product on insulin
sensitivity in horses. ANIMALS: 8 healthy mature horses. PROCEDURES :Horses (n =
4/group) received a basal diet without (control diet) or with docosahexaenoic
acid-rich microalgae meal (150 g/d) for 49 days (day 0 = first day of diet). On
day 28, an isoglycemic hyperinsulinemic clamp procedure was performed. Horses
then received dexamethasone (0.04 mg/kg/d) for 21 days. On day 49, the clamp
procedure was repeated. After a 60-day washout, horses received the alternate
diet, and procedures were repeated. Plasma fatty acid, glucose, and insulin
concentrations and glucose and insulin dynamics during the clamp procedure were
measured on days 28 and 49. Two estimates of insulin sensitivity (reciprocal of
the square root of the insulin concentration and the modified insulin-to-glucose
ratio for ponies) were calculated. RESULTS: Baseline glucose and insulin
concentrations or measures of insulin sensitivity on day 28 did not differ
between horses when fed the control diet or the basal diet plus microalgae meal.
On day 49 (ie, after dexamethasone administration), the microalgae meal was
associated with lower baseline insulin and glucose concentrations and an improved
modified insulin-to-glucose ratio for ponies, compared with results for the
control diet. CONCLUSIONS AND CLINICAL RELEVANCE: Although the microalgae meal
had no effect on clamp variables following dexamethasone treatment, it was
associated with improved plasma glucose and insulin concentrations and insulin
sensitivity estimates. A role for microalgae in the nutritional management of
insulin-resistant horses warrants investigation.
PMID- 26413828
TI - Use of indocyanine green and sodium fluorescein for anterior segment angiography
in ophthalmologically normal cats.
AB - OBJECTIVE: To assess and compare results of anterior segment angiography of
ophthalmologically normal cats following IV injection with indocyanine green and
sodium fluorescein dyes. ANIMALS: 10 client-owned cats. PROCEDURES: Anterior
segment angiography was performed in anesthetized cats following administration
of 0.25% indocyanine green (1.0 mg/kg, IV) or 10% sodium fluorescein (20 mg/kg,
IV) solution. All cats received both treatments. Imaging (1 eye/cat) was
performed with a full-spectrum digital single-lens reflex camera equipped with an
adaptor (1 image/s for 30 seconds) immediately following IV dye injection and 1,
2, 3, 4, and 5 minutes after injection. Onset and duration of arterial,
capillary, and venous phases of iris vasculature were identified and compared
statistically between treatments. Degree of iridal pigmentation, leakage of dye
from iris vasculature, and image quality were subjectively assessed. RESULTS: No
differences were found in onset or duration of vascular phases between
treatments. Visibility of the iris vasculature was not impaired by poor or
moderate iridal pigmentation with either method. Indocyanine green provided
subjectively better vascular detail and image contrast than sodium fluorescein.
No vascular dye leakage was observed following indocyanine green administration.
Leakage of dye from blood vessels in the stroma (in 10 cats) and presence of dye
in the anterior chamber (in 5 cats) were detected after sodium fluorescein
administration. CONCLUSIONS AND CLINICAL RELEVANCE: Images obtained with either
fluorescent dye were considered to be of diagnostic quality. Lack of leakage
following indocyanine green administration suggested this treatment may have
better diagnostic utility for anterior segment angiography. The photographic
equipment used provided a cost-effective alternative to existing imaging systems.
PMID- 26413829
TI - Effect of laser treatment on first-intention incisional wound healing in ball
pythons (Python regius).
AB - OBJECTIVE: To evaluate effects of laser treatment on incisional wound healing in
ball pythons (Python regius). ANIMALS: 6 healthy adult ball pythons. PROCEDURES:
Snakes were sedated, a skin biopsy specimen was collected for histologic
examination, and eight 2-cm skin incisions were made in each snake; each incision
was closed with staples (day 0). Gross evaluation of all incision sites was
performed daily for 30 days, and a wound score was assigned. Four incisions of
each snake were treated (5 J/cm(2) and a wavelength of 980 nm on a continuous
wave sequence) by use of a class 4 laser once daily for 7 consecutive days; the
other 4 incisions were not treated. Two excisional skin biopsy specimens (1
control and 1 treatment) were collected from each snake on days 2, 7, 14, and 30
and evaluated microscopically. Scores were assigned for total inflammation,
degree of fibrosis, and collagen maturity. Generalized linear models were used to
investigate the effect of treatment on each variable. RESULTS: Wound scores for
laser-treated incisions were significantly better than scores for control
incisions on day 2 but not at other time points. There were no significant
differences in necrosis, fibroplasia, inflammation, granuloma formation, or
bacterial contamination between control and treatment groups. Collagen maturity
was significantly better for the laser-treated incisions on day 14. CONCLUSIONS
AND CLINICAL RELEVANCE: Laser treatment resulted in a significant increase in
collagen maturity at day 14 but did not otherwise significantly improve healing
of skin incisions.
PMID- 26413830
TI - Anti-bovine herpesvirus and anti-bovine viral diarrhea virus antibody responses
in pregnant Holstein dairy cattle following administration of a multivalent
killed virus vaccine.
AB - OBJECTIVE: To determine the effect of a commercially available multivalent killed
virus vaccine on serum neutralizing (SN) and colostrum neutralizing (CN)
antibodies against bovine herpesvirus (BHV) type 1 and bovine viral diarrhea
virus (BVDV) types 1 and 2 in pregnant dairy cattle. ANIMALS: 49 Holstein dairy
cattle. PROCEDURES :25 cattle were vaccinated (IM injection) at least 60 days
prior to calving (ie, at the end of the lactation period or according to the
expected calving date for heifers) and again 5 weeks later. The remaining 24
cattle were not vaccinated (control group). Titers of SN antibodies were measured
at the 5-week time point. Titers of SN and CN antibodies were measured at
parturition. RESULTS: 5 weeks after initial vaccination, titers of SN antibodies
against BHV-1 and BVDV types 1 and 2 were 1:512, 1:128, and 1:2,048,
respectively, in vaccinates and 1:64, 1:128, and 1:64, respectively, in
unvaccinated controls. Equivalent SN antibody titers at parturition were 1:256,
1:64, and 1:512, respectively, in vaccinates and 1:128, 1:128, and 1:64,
respectively, in controls. Median titers of CN antibodies against BHV-1 and BVDV
types 1 and 2 were 1:1,280, 1:10,240, and 1:20,480, respectively, in vaccinates
and 1:80, 1:1,280, and 1:2,560, respectively, in controls. CONCLUSIONS AND
CLINICAL RELEVANCE: Titers of antibodies against viral respiratory pathogens were
significantly enhanced in both serum (BHV-1 and BVDV type 2) and colostrum (BHV-1
and BVDV types 1 and 2) in cattle receiving a killed virus vaccine (with no
adverse reactions) before parturition. To maximize protection of bovine neonates,
this method of vaccination should be considered.
PMID- 26413831
TI - Preoperative Decision Making for Nephron-Sparing Procedure in the Renal Mass:
Time for Using Standard Tools?
AB - OBJECTIVE: To determine if the application of using standard tools on tumor
complexity and comorbidity indexes may replace the traditional choice of nephron
sparing procedure (NSP) based on clinical maximal tumor diameter (cMTD), age, and
comorbidity. PATIENTS AND METHODS: Anatomic complexity scores (PADUA and RENAL)
and Charlson comorbidity index (CCI) and CCI age-adjusted (CACI) were applied to
261 cases of either nephron-sparing surgery (NSS) or cryoablation (CA). Patient-
and tumor-related preoperative variables, PADUA, RENAL, CCI, and CACI, were
evaluated for their association and as treatment predictors in uni- and
multivariate regression analysis. Discriminative ability of each of the models
generated was compared for their receiver operating curve area under the curve
(AUC). Survival analysis was performed using log rank tests. RESULTS: In total,
124 cases underwent partial nephrectomy and 137 cases CA. cMTD, RENAL, PADUA,
age, and CACI were independently associated with the choice of NSS. Five models
integrating a combination of age, cMTD, CACI, PADUA, and RENAL (scores and
complexity groups) showed an AUC >0.72 to predict the odds of receiving NSS. The
discriminative ability of these five models was not statistically significantly
different. CONCLUSIONS: cMTD, RENAL, PADUA, age, and CACI are preoperative
variables independently associated with the choice of NSP. Models incorporating
tools on tumor anatomic complexity and CACI may replace the decision-making in
the type of NSP based on cMTD and age. The use of these models can be of value
for future standardization and comparison.
PMID- 26413833
TI - Clinical Significance of Prenatal and Postnatal Heavily T2-Weighted Magnetic
Resonance Images in Patients with Myelomeningocele.
AB - PURPOSE: To compare the utility and limitations of prenatal magnetic resonance
(MR) imaging using half-Fourier acquisition single-shot turbo spin-echo (HASTE)
with postnatal heavily T2-weighted imaging (hT2WI) for the evaluation of central
nervous system abnormalities associated with myelomeningocele (MMC). METHODS:
Sixteen patients with MMC who had undergone pre- and postnatal MR imaging were
included in this study. MR imaging, including HASTE, was undertaken in the 3rd
trimester, and hT2WI was performed immediately after delivery. The precision with
which each could distinguish MMC, hindbrain herniation and ventriculomegaly was
compared retrospectively. RESULTS: The skin defects and MMC sacs were clearly
visible on prenatal HASTE images, although it was difficult to identify precisely
the level of MMC compared with postnatal hT2WI, in which the detailed anatomical
relationships of the spinal cord, neural placode and ventral nerve roots were
evident in every case. Hindbrain herniation could be visualized on prenatal HASTE
images, although its severity was difficult to evaluate because of the small size
of the structures and neck flexion; again, the resolution was superior on
postnatal hT2WI. For hydrocephalus, there were no significant differences in the
diagnostic precision and ability to grade the severity between pre- and postnatal
imaging. CONCLUSION: Prenatal HASTE imaging permits the diagnosis and
understanding of the gross anatomy of MMC and associated hindbrain herniation and
ventriculomegaly, but postnatal hT2WI is superior for evaluating detailed
anatomy.
PMID- 26413834
TI - Control of Neuronal Network in Caenorhabditis elegans.
AB - Caenorhabditis elegans, a soil dwelling nematode, is evolutionarily rudimentary
and contains only ~ 300 neurons which are connected to each other via chemical
synapses and gap junctions. This structural connectivity can be perceived as
nodes and edges of a graph. Controlling complex networked systems (such as
nervous system) has been an area of excitement for mankind. Various methods have
been developed to identify specific brain regions, which when controlled by
external input can lead to achievement of control over the state of the system.
But in case of neuronal connectivity network the properties of neurons identified
as driver nodes is of much importance because nervous system can produce a
variety of states (behaviour of the animal). Hence to gain insight on the type of
control achieved in nervous system we implemented the notion of structural
control from graph theory to C. elegans neuronal network. We identified 'driver
neurons' which can provide full control over the network. We studied phenotypic
properties of these neurons which are referred to as 'phenoframe' as well as the
'genoframe' which represents their genetic correlates. We find that the driver
neurons are primarily motor neurons located in the ventral nerve cord and
contribute to biological reproduction of the animal. Identification of driver
neurons and its characterization adds a new dimension in controllability of C.
elegans neuronal network. This study suggests the importance of driver neurons
and their utility to control the behaviour of the organism.
PMID- 26413836
TI - Development and Validation of the Scan of Postgraduate Educational Environment
Domains (SPEED): A Brief Instrument to Assess the Educational Environment in
Postgraduate Medical Education.
AB - INTRODUCTION: Current instruments to evaluate the postgraduate medical
educational environment lack theoretical frameworks and are relatively long,
which may reduce response rates. We aimed to develop and validate a brief
instrument that, based on a solid theoretical framework for educational
environments, solicits resident feedback to screen the postgraduate medical
educational environment quality. METHODS: Stepwise, we developed a screening
instrument, using existing instruments to assess educational environment quality
and adopting a theoretical framework that defines three educational environment
domains: content, atmosphere and organization. First, items from relevant
existing instruments were collected and, after deleting duplicates and items not
specifically addressing educational environment, grouped into the three domains.
In a Delphi procedure, the item list was reduced to a set of items considered
most important and comprehensively covering the three domains. These items were
triangulated against the results of semi-structured interviews with 26 residents
from three teaching hospitals to achieve face validity. This draft version of the
Scan of Postgraduate Educational Environment Domains (SPEED) was administered to
residents in a general and university hospital and further reduced and validated
based on the data collected. RESULTS: Two hundred twenty-three residents
completed the 43-item draft SPEED. We used half of the dataset for item
reduction, and the other half for validating the resulting SPEED (15 items, 5 per
domain). Internal consistencies were high. Correlations between domain scores in
the draft and brief versions of SPEED were high (>0.85) and highly significant
(p<0.001). Domain score variance of the draft instrument was explained for >=80%
by the items representing the domains in the final SPEED. CONCLUSIONS: The SPEED
comprehensively covers the three educational environment domains defined in the
theoretical framework. Because of its validity and brevity, the SPEED is
promising as useful and easily applicable tool to regularly screen educational
environment quality in postgraduate medical education.
PMID- 26413837
TI - Radiation-induced resistance oscillations in a 2D hole gas: a demonstration of a
universal effect.
AB - We report on a theoretical study about the microwave-induced resistance
oscillations and zero resistance states when dealing with p-type semiconductors
and holes instead of electrons. We consider a high-mobility two-dimensional hole
gas hosted in a pure Ge/SiGe quantum well. Similarly to electrons we obtain
radiation-induced resistance oscillations and zero resistance states. We
analytically deduce a universal expression for the irradiated magnetoresistance,
explaining the origin of the minima positions and their 1/4 cycle phase shift.
The outcome is that these phenomena are universal and only depend on radiation
and cyclotron frequencies. We also study the possibility of having simultaneously
two different carriers driven by radiation: light and heavy holes. As a result
the calculated magnetoresistance reveals an interference profile due to the
different effective masses of the two types of carriers.
PMID- 26413835
TI - The speed of swelling kinetics modulates cell volume regulation and calcium
signaling in astrocytes: A different point of view on the role of aquaporins.
AB - Regulatory volume decrease (RVD) is a process by which cells restore their
original volume in response to swelling. In this study, we have focused on the
role played by two different Aquaporins (AQPs), Aquaporin-4 (AQP4), and Aquaporin
1 (AQP1), in triggering RVD and in mediating calcium signaling in astrocytes
under hypotonic stimulus. Using biophysical techniques to measure water flux
through the plasma membrane of wild-type (WT) and AQP4 knockout (KO) astrocytes
and of an astrocyte cell line (DI TNC1) transfected with AQP4 or AQP1, we here
show that AQP-mediated fast swelling kinetics play a key role in triggering and
accelerating RVD. Using calcium imaging, we show that AQP-mediated fast swelling
kinetics also significantly increases the amplitude of calcium transients
inhibited by Gadolinium and Ruthenium Red, two inhibitors of the transient
receptor potential vanilloid 4 (TRPV4) channels, and prevented by removing
extracellular calcium. Finally, inhibition of TRPV4 or removal of extracellular
calcium does not affect RVD. All together our study provides evidence that (1)
AQP influenced swelling kinetics is the main trigger for RVD and in mediating
calcium signaling after hypotonic stimulus together with TRPV4, and (2) calcium
influx from the extracellular space and/or TRPV4 are not essential for RVD to
occur in astrocytes.
PMID- 26413838
TI - Diminished Chondrogenesis and Enhanced Osteoclastogenesis in Leptin-Deficient
Diabetic Mice (ob/ob) Impair Pathologic, Trauma-Induced Heterotopic Ossification.
AB - Diabetic trauma patients exhibit delayed postsurgical wound, bony healing, and
dysregulated bone development. However, the impact of diabetes on the pathologic
development of ectopic bone or heterotopic ossification (HO) following trauma is
unknown. In this study, we use leptin-deficient mice as a model for type 2
diabetes to understand how post-traumatic HO development may be affected by this
disease process. Male leptin-deficient (ob/ob) or wild-type (C57BL/6 background)
mice aged 6-8 weeks underwent 30% total body surface area burn injury with left
hind limb Achilles tenotomy. Micro-CT (MUCT) imaging showed significantly lower
HO volumes in diabetic mice compared with wild-type controls (0.70 vs. 7.02
mm(3), P < 0.01) 9 weeks after trauma. Ob/ob mice showed evidence of HO
resorption between weeks 5 and 9. Quantitative real time PCR (qRT-PCR)
demonstrated high Vegfa levels in ob/ob mice, which was followed by disorganized
vessel growth at 7 weeks. We noted diminished chondrogenic gene expression (SOX9)
and diminished cartilage formation at 5 days and 3 weeks, respectively. Tartrate
resistant acid phosphatase stain showed increased osteoclast presence in normal
native bone and pathologic ectopic bone in ob/ob mice. Our findings suggest that
early diminished HO in ob/ob mice is related to diminished chondrogenic
differentiation, while later bone resorption is related to osteoclast presence.
PMID- 26413839
TI - Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.
AB - Recent studies indicate that the abnormal microenvironment of tumors may play a
critical role in carcinogenesis, including lung cancer. We comprehensively
assessed the number of stromal cells, especially immune/inflammatory cells, in
lung cancer and evaluated their infiltration in cancers of different stages,
types and metastatic characteristics potential. Immunohistochemical analysis of
lung cancer tissue arrays containing normal and lung cancer sections was
performed. This analysis was combined with cyto-/histomorphological assessment
and quantification of cells to classify/subclassify tumors accurately and to
perform a high throughput analysis of stromal cell composition in different types
of lung cancer. In human lung cancer sections we observed a significant
elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T
helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+),
mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells,
myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared
with healthy donor specimens. We observed all of these immune cell markers in
different types of lung cancers including squamous cell carcinoma,
adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary
adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The
numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III
cancer specimens was significantly greater than those in stage I samples. We
observed substantial stage-dependent immune cell infiltration in human lung
tumors suggesting that the tumor microenvironment plays a critical role during
lung carcinogenesis. Strategies for therapeutic interference with lung cancer
microenvironment should consider the complexity of its immune cell composition.
PMID- 26413841
TI - Right-to-try laws: hope, hype, and unintended consequences.
PMID- 26413843
TI - Correction: Effects of Reducing Antimicrobial Use and Applying a Cleaning and
Disinfection Program in Veal Calf Farming: Experiences from an Intervention Study
to Control Livestock-Associated MRSA.
PMID- 26413840
TI - The Impact of Midcervical Contusion Injury on Diaphragm Muscle Function.
AB - Midcervical contusion injuries disrupt descending ipsilateral excitatory
bulbospinal projections to phrenic motoneurons, compromising ventilation. We
hypothesized that a unilateral contusion injury at C3 versus C5 would
differentially impact phrenic activity reflecting more prominent disruption of
ipsilateral descending excitatory drive to more caudal segments of the phrenic
motor pool with more cranial injuries. Phrenic motoneuron counts and evidence of
diaphragm muscle denervation at individual neuromuscular junctions (NMJ) were
evaluated at 14 days post-injury after unilateral contusion injury (100 kDynes).
Whole body plethysmography and chronic diaphragm EMG were measured before the
injury and at 3, 7, and 14 days post-injury. Contusion injuries at either level
resulted in a similarly sized cavity. C3 contusion resulted in loss of 39 +/- 13%
of ipsilateral phrenic motoneurons compared with 13 +/- 21% after C5 contusion (p
= 0.003). Cervical contusion injuries resulted in diaphragm muscle denervation
(C3 contusion: 17 +/- 4%; C5 contusion: 7 +/- 4%; p = 0.047). The pattern of
denervation revealed segmental innervation of the diaphragm muscle, with greater
denervation ventrally after C3 contusion and dorsally after C5 contusion.
Overall, diaphragm root mean square electromyography activity did not change
ipsilaterally after C3 or C5 contusion, but increased contralaterally (~ 11%)
after C3 contusion only on the first day post-injury (p = 0.026). Similarly,
there were no significant changes in breathing parameters during eupnea or
exposure to hypoxia (10% O2) - hypercapnia (5% CO2) at any time post-injury.
Unilateral midcervical contusions minimally impair ventilatory behaviors despite
phrenic motoneuron loss and diaphragm muscle denervation.
PMID- 26413842
TI - Relation of Step Length to Magnetic Resonance Imaging-Detected Structural Damage
in the Patellofemoral Joint: The Multicenter Osteoarthritis Study.
AB - OBJECTIVE: To investigate the relationship of step length to the sex-specific
prevalence and worsening of magnetic resonance imaging (MRI)-detected structural
damage in the patellofemoral (PF) joint among a cohort of older women and men
with or at risk of knee osteoarthritis (OA). METHODS: The Multicenter
Osteoarthritis Study is a cohort study of persons ages 50-79 years with or at
risk of knee OA. Step length was assessed using the GAITRite walkway (CIR
Systems) at the 60-month visit, and cartilage damage and bone marrow lesions
(BMLs) were graded on MRI at the 60- and 84-month visits. Step length was divided
into sex-specific quintiles, and the relationship of step length to the
prevalence and worsening of cartilage damage and BMLs in the PF joint was
examined using logistic regression, adjusting for age, body mass index (BMI), leg
length, and tibiofemoral joint structural damage. RESULTS: In 1,053 knees, 4,094
and 4,083 PF joint subregions were studied for the cartilage and BML analyses,
respectively. Mean +/- SD age was 65.6 +/- 8.1 years and mean +/- SD BMI was 29.1
+/- 4.7 kg/m(2) ; 62% of participants were female. In women, compared to those
with the shortest step length, those with the longest step length had 0.62 (95%
confidence interval [95% CI] 0.43-0.88) and 0.59 (95% CI 0.40-0.87) times the
odds of cartilage damage and BMLs, respectively. There was no cross-sectional
association in men, and no longitudinal association in either sex. CONCLUSION:
Women with PF joint structural damage may adapt their gait by shortening their
step length, but this may not be sufficient to reduce the risk of worsening
damage over time.
PMID- 26413844
TI - Magnetotransport Properties of Epitaxial Ge/AlAs Heterostructures Integrated on
GaAs and Silicon.
AB - The magnetotransport properties of epitaxial Ge/AlAs heterostructures with
different growth conditions and substrate architectures have been studied under
+/-9 T magnetic field and at 390 mK temperature. Systematic mobility measurements
of germanium (Ge) epilayers grown on GaAs substrates at growth temperatures from
350 to 450 degrees C allow us to extract a precise growth window for device
quality Ge, corroborated by structural and morphological properties. Our results
on Si substrate using a composite metamorphic AlAs/GaAs buffer at 400 degrees C
Ge growth temperature, show that the Ge/AlAs system can be tailored to have a
single carrier transport while keeping the charge solely in the Ge layer. Single
carrier transport confined to the Ge layer is demonstrated by the weak
localization quantum correction to the conductivity observed at low magnetic
fields and 390 mK temperature. The weak localization effect points to a near
absence of spin-orbit interaction for carriers in the electronically active layer
and is used here for the first time to pinpoint Ge as this active layer. Thus,
the epitaxial Ge grown on Si using AlAs/GaAs buffer architecture is a promising
candidate for next-generation energy-efficient fin field-effect transistor
applications.
PMID- 26413845
TI - Systolic Anterior Motion of the Mitral Valve Triggered by the Intra-Aortic
Balloon Pump.
PMID- 26413847
TI - Brief Report: Prevalence of Latent Rheumatic Heart Disease Among HIV-Infected
Children in Kampala, Uganda.
AB - Rheumatic heart disease (RHD) remains highly prevalent in resource-constrained
settings around the world, including countries with high rates of HIV/AIDS.
Although both are immune-mediated diseases, it is unknown whether HIV modifies
the risk or progression of RHD. We performed screening echocardiography to
determine the prevalence of latent RHD in 488 HIV-infected children aged 5-18 in
Kampala, Uganda. The overall prevalence of borderline/definite RHD was 0.82% (95%
confidence interval: 0.26% to 2.23%), which is lower than the published
prevalence rates of 1.5%-4% among Ugandan children. There may be protective
factors that decrease the risk of RHD in HIV-infected children.
PMID- 26413846
TI - Prevalence of Transmitted HIV Drug Resistance Among Recently Infected Persons in
San Diego, CA 1996-2013.
AB - BACKGROUND: Transmitted drug resistance (TDR) remains an important concern when
initiating antiretroviral therapy (ART). Here, we describe the prevalence and
phylogenetic relationships of TDR among ART-naive, HIV-infected individuals in
San Diego from 1996 to 2013. METHODS: Data were analyzed from 496 participants of
the San Diego Primary Infection Cohort who underwent genotypic resistance testing
before initiating therapy. Mutations associated with drug resistance were
identified according to the WHO-2009 surveillance list. Network and phylogenetic
analyses of the HIV-1 pol sequences were used to evaluate the relationships of
TDR within the context of the entire cohort. RESULTS: The overall prevalence of
TDR was 13.5% (67/496), with an increasing trend over the study period (P =
0.005). TDR was predominantly toward nonnucleoside reverse transcriptase
inhibitors (NNRTIs) [8.5% (42/496)], also increasing over the study period (P =
0.005). By contrast, TDR to protease inhibitors and nucleos(t)ide reverse
transcriptase inhibitors were 4.4% (22/496) and 3.8% (19/496), respectively, and
did not vary with time. TDR prevalence did not differ by age, gender,
race/ethnicity, or risk factors. Using phylogenetic analysis, we identified 52
transmission clusters, including 8 with at least 2 individuals sharing the same
mutation, accounting for 23.8% (16/67) of the individuals with TDR. CONCLUSIONS:
Between 1996 and 2013, the prevalence of TDR significantly increased among
recently infected ART-naive individuals in San Diego. Around one-fourth of TDR
occurred within clusters of recently infected individuals. These findings
highlight the importance of baseline resistance testing to guide selection of ART
and for public health monitoring.
PMID- 26413848
TI - Implementation and Operational Research: Programmatic Feasibility of Dried Blood
Spots for the Virological Follow-up of Patients on Antiretroviral Treatment in
Nord Kivu, Democratic Republic of the Congo.
AB - BACKGROUND: As part of its policy to shift monitoring of antiretroviral therapy
(ART) to primary health care (PHC) workers, the Ministry of Health of the
Democratic Republic of Congo (DRC) tested the feasibility of using dried blood
spots (DBS) for viral load (VL) quantification and genotypic drug resistance
testing in off-site high-throughput laboratories. METHODS: DBS samples from
adults on ART were collected in 13 decentralized PHC facilities in the Nord-Kivu
province and shipped during program quarterly supervision to a reference
laboratory 2000 km away, where VL was quantified with a commercial assay
(m2000rt, Abbott). A second DBS was sent to a World Health Organization (WHO)
accredited laboratory for repeat VL quantification on a subset of samples with a
generic assay (Biocentric) and genotypic drug resistance testing when VL >1000
copies per milliliter. FINDINGS: Constraints arose because of an interruption in
national laboratory funding rather than to technical or logistic problems. All
samples were assessed by both VL assays to allow ART adjustment. Median DBS
turnaround time was 37 days (interquartile range: 9-59). Assays performed
unequally with DBS, impacting clinical decisions, quality assurance, and overall
cost-effectiveness. Based on m2000rt or generic assay, 31.3% of patients were on
virological failure (VF) and 14.8% presented resistance mutations versus 50.3%
and 15.4%, respectively. CONCLUSION: This study confirms that current
technologies involving DBS make virological monitoring of ART possible at PHC
level, including in challenging environments, provided organizational issues are
addressed. Adequate core funding of HIV laboratories and adapted choice of VL
assays require urgent attention to control resistance to ART as coverage expands.
PMID- 26413849
TI - Mucosal Topical Microbicide Candidates Exert Influence on the Subsequent SIV
Infection and Survival by Regulating SIV-Specific T-Cell Immune Responses.
AB - OBJECTIVE: To determine whether mucosal topical microbicides have any influence
on disease progression during subsequent simian immunodeficiency virus (SIV)
infection. DESIGN: A 2-phase study was performed in primate monkeys. The first
phase mimicked microbicide efficacy studies; the second phase served to determine
the disease progression in a productive infection model. METHODS: During the
first phase, monkeys were intrarectally pretreated with tenofovir, sifuvirtide
(SFT), or maraviroc-formulated microbicides and then challenged with low-dose
SHIV-1157ipd3N4. Second, all monkeys were rechallenged with a single high dose of
SIVmac239 to generate productive infections. The survival rate, viral loads,
CD4(+) T-cell counts, and SIV-specific T-cell responses were determined during
the 104-week following up. RESULTS: Repeated rectal challenges did not result in
productive infection in all groups, evidenced by undetectable viral loads with
occasional viral blips during the first phase of this study. All monkeys were
productively infected after the high-dose rechallenge with SIVmac239. Two groups,
including maraviroc-treated and tenofovir-treated groups, experienced 100%
mortality during the 104-week following up. In contrast, the SFT-treated group
showed significantly higher survival, and only 25% died at week 95.
Interestingly, SIV-specific T-cell responses were also significantly higher in
the SFT group. Transcriptomic analyses evidenced immune imprint in immune system
among different microbicide-treated groups. CONCLUSIONS: This study provides
preliminary but important evidence for the influence of prophylactically applied
microbicides on disease progression of subsequent SIV infection and suggests that
the long-term immune safety concern for microbicides should be also considered in
the effort to develop effective microbicides.
PMID- 26413851
TI - V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1.
AB - BACKGROUND: Highly potent broadly neutralizing monoclonal antibodies (bNAbs) have
been obtained from individuals infected by HIV-1 group M variants. We analyzed
the cross-group neutralization potency of these bNAbs toward non-M primary
isolates (PI). MATERIAL AND METHODS: The sensitivity to neutralization was
analyzed in a neutralization assay using TZM-bl cells. Twenty-three bNAbs were
used, including reagents targeting the CD4-binding site, the N160 glycan-V1/V2
site, the N332 glycan-V3 site, the membrane proximal external region of gp41, and
complex epitopes spanning both env subunits. Two bispecific antibodies that
combine the inhibitory activity of an anti-CD4 with that of PG9 or PG16 bNAbs
were included in the study (PG9-iMab and PG16-iMab). RESULTS: Cross-group
neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2
site. Four group O PIs, 1 group N PI, and the group P PI were neutralized by PG9
and/or PG16 or PGT145 at low concentrations (0.04-9.39 MUg/mL). None of the non-M
PIs was neutralized by the bNAbs targeting other regions at the highest
concentration tested, except 10E8 that neutralized weakly 2 group N PIs and 35O22
that neutralized 1 group O PI. The bispecific bNAbs neutralized very efficiently
all the non-M PIs with IC50 below 1 MUg/mL, except 2 group O strains. CONCLUSION:
The N160 glycan-V1/V2 site is the most conserved neutralizing site within the 4
groups of HIV-1. This makes it an interesting target for the development of HIV
vaccine immunogens. The corresponding bNAbs may be useful for immunotherapeutic
strategies in patients infected by non-M variants.
PMID- 26413850
TI - Effect of Depot Medoxyprogesterone Acetate on Immune Functions and Inflammatory
Markers of HIV-Infected Women.
AB - OBJECTIVES: Depot medroxyprogesterone acetate (DMPA) was associated with
increased HIV transmission and accelerated disease progression in untreated
women. The potential underlying mechanisms include immune modulation. We
evaluated the effect of a single DMPA injection on cell-mediated immunity (CMI),
T-cell activation, T-cell regulation (Treg), and inflammation in HIV-infected
women on combination antiretroviral regimen (cART). METHODS: Women with HIV
plasma RNA <= 400 copies per milliliter on stable cART received DMPA and had
immunologic and medroxyprogesterone acetate (MPA) measurements at baseline, 4
weeks [peak MPA concentration (Cmax)], and 12 weeks [highest MPA area under the
concentration curve]. RESULTS: At baseline, among 24 women with median age of 32
years and 622 CD4(+) cells per microliter, >= 68% had HIV, varicella-zoster
virus, phytohemagglutinin A and CD3/CD28 CMI measured by lymphocyte
proliferation, and/or IFNgamma/IL2 dual-color fluorospot. CMI did not
significantly change after DMPA administration except for a 1.4-fold increase in
IL2/IFNgamma varicella-zoster virus fluorospot at week 12. T-cell activation
decreased after DMPA administration, reaching statistical significance at week 12
for CD4(+)CD25+%. Treg behaved heterogeneously with an increase in CD8+FOXP3+% at
week 4 and a decrease in CD4+IL35+% at week 12. There was a decrease in TGFbeta
at week 12 and no other changes in plasma biomarkers. Correlation analyses showed
that high MPA Cmax and/or area under the concentration curve were significantly
associated with increases of IFNgamma HIV enzyme-linked ImmunoSpot, CD4+IL35+%,
and CD4+TGFbeta+% Treg and decreases of plasma IL10 from baseline to weeks 4
and/or 12. CONCLUSIONS: A single dose of DMPA did not have immune-suppressive or
pro-inflammatory effects in HIV-infected women on cART. Additional studies need
to assess the effect of multiple doses.
PMID- 26413852
TI - Lower HIV Risk Among Circumcised Men Who Have Sex With Men in China: Interaction
With Anal Sex Role in a Cross-Sectional Study.
AB - BACKGROUND: Voluntary medical male circumcision reduces the risk of HIV
heterosexual transmission in men, but its effect on male-to-male sexual
transmission is uncertain. METHODS: Circumcision status of men who have sex with
men (MSM) in China was evaluated by genital examination and self-report; anal
sexual role was assessed by questionnaire interview. Serostatus for HIV and
syphilis was confirmed. RESULTS: Among 1155 participants (242 were seropositive
and 913 with unknown HIV status at enrollment), the circumcision rate by self
report (10.4%) was higher than confirmed by genital examination (8.2%). Male
circumcision (by examination) was associated with 47% lower odds of being HIV
seropositive [adjusted odds ratio (aOR): 0.53; 95% confidence interval (CI): 0.27
to 1.02] after adjusting for demographic covariates, number of lifetime male
sexual partners, and anal sex role. Among MSM who predominantly practiced
insertive anal sex, circumcised men had 62% lower odds of HIV infection than
those who were uncircumcised (aOR: 0.38; 95% CI: 0.09 to 1.64). Among those whose
anal sex position was predominantly receptive or versatile, circumcised men have
46% lower odds of HIV infection than did men who were not circumcised (aOR: 0.54;
95% CI: 0.25 to 1.14). Compared to uncircumcised men reporting versatile or
predominantly receptive anal sex positioning, those who were circumcised and
reported practicing insertive sex had an 85% lower risk (aOR: 0.15; 95% CI: 0.04
to 0.65). Circumcision was not associated clearly with lower syphilis risk (aOR:
0.91; 95% CI: 0.51 to 1.61). CONCLUSIONS: Circumcised MSM were less likely to
have acquired HIV, most pronounced among men predominantly practicing insertive
anal intercourse. A clinical trial is needed.
PMID- 26413854
TI - Microbiota-Dependent Marker TMAO Is Elevated in Silent Ischemia but Is Not
Associated With First-Time Myocardial Infarction in HIV Infection.
AB - OBJECTIVES: HIV infection is associated with increased risk of coronary heart
disease beyond that explained by traditional risk factors, and altered gut
microbiota has been proposed as a potential trigger. Trimethylamine-N-oxide
(TMAO) is a proatherogenic substance formed in the liver from trimethylamine,
exclusively generated by gut microbiota from dietary phosphatidylcholine. We
aimed to investigate whether TMAO is associated with subclinical and clinical
coronary heart disease in HIV infection. METHODS: Two previously described
cohorts were examined as follows: (1) cross-sectional cohort of HIV-infected
persons and uninfected controls with known atherosclerotic plaque burden as
assessed by myocardial perfusion scintigraphy, coronary artery calcium score, and
intima-media thickness and (2) nested case-control study of HIV-infected persons
with first-time myocardial infarction (MI) compared with HIV-infected persons
without MI, assessed at 4 time points from before initiation of antiretroviral
therapy (ART) to last sample before the case's MI (median: 51, range: 0-239
days). RESULTS: There was no difference in plasma TMAO when comparing HIV
infected persons and uninfected controls. TMAO was elevated in HIV-infected
persons with myocardial perfusion defects but was not associated with coronary
artery calcium score, intima media thickness, or Framingham risk score. In the
nested case control study, plasma TMAO was not associated with first-time MI.
However, TMAO increased after ART introduction and was associated with the use of
protease inhibitors in both cohorts. CONCLUSIONS: TMAO was elevated in HIV
infected persons with myocardial perfusion defects, but was not associated with
first-time MI. Our data question TMAO as a useful biomarker of cardiovascular
risk in HIV infection, at least in ART-treated individuals.
PMID- 26413853
TI - The Safety of Tenofovir-Emtricitabine for HIV Pre-Exposure Prophylaxis (PrEP) in
Individuals With Active Hepatitis B.
AB - BACKGROUND: Pre-exposure prophylaxis (PrEP) with daily oral emtricitabine and
tenofovir disoproxil fumarate (FTC/TDF) prevents HIV infection. The safety and
feasibility of HIV PrEP in the setting of hepatitis B virus (HBV) infection were
evaluated. METHODS: The Iniciativa Profilaxis Pre-Exposicion study randomized
2499 HIV-negative men and transgender women who have sex with men to once-daily
oral FTC/TDF versus placebo. Hepatitis serologies and transaminases were obtained
at screening and at the time PrEP was discontinued. HBV DNA was assessed by
polymerase chain reaction, and drug resistance was assessed by population
sequencing. Vaccination was offered to individuals susceptible to HBV infection.
RESULTS: Of the 2499 participants, 12 (0.5%; including 6 randomized to FTC/TDF)
had chronic HBV infection. After stopping FTC/TDF, 5 of the 6 participants in the
active arm had liver function tests performed at follow-up. Liver function tests
remained within normal limits at post-stop visits except for a grade 1 elevation
in 1 participant at post-stop week 12 (alanine aminotransferase = 90, aspartate
aminotransferase = 61). There was no evidence of hepatic flares. Polymerase chain
reaction of stored samples showed that 2 participants in the active arm had
evidence of acute HBV infection at enrollment. Both had evidence of grade 4
transaminase elevations with subsequent resolution. Overall, there was no
evidence of TDF or FTC resistance among tested genotypes. Of 1633 eligible for
vaccination, 1587 (97.2%) received at least 1 vaccine; 1383 (84.7%) completed the
series. CONCLUSIONS: PrEP can be safely provided to individuals with HBV
infection if there is no evidence of cirrhosis or substantial transaminase
elevation. HBV vaccination rates at screening were low globally, despite
recommendations for its use, yet uptake and efficacy were high when offered.
PMID- 26413855
TI - Thiazyl Trifluoride (NSF3) Adducts and Imidodifluorosulfate (F2OSN-) Derivatives
of Hg(OTeF5)2.
AB - Reactions of Hg(OTeF5)2 with excess amounts of NSF3 at 0 degrees C result in the
formation of NSF3 adducts having the compositions [Hg(OTeF5)2.N=SF3]infinity (1),
[Hg(OTeF5)2.2N=SF3]2 (2), and Hg3(OTeF5)6.4N=SF3 (3). When the reactions are
carried out at room temperature, oxygen/fluorine metatheses occur yielding the
F2OSN- derivatives [Hg(OTeF5)(N?SOF2).N=SF3]infinity (4) and
[Hg3(OTeF5)5(N?SOF2).2N=SF3]2 (5). The proposed reaction pathway leading to F2OSN
group formation occurs by nucleophilic attack by a F5TeO- group at the
sulfur(VI) atom of NSF3, followed by TeF6 elimination. Tellurium hexafluoride
formation was confirmed by (19)F NMR spectroscopy. The NSF3 molecules are
terminally N-coordinated to mercury, whereas the F2OSN- ligands are N-bridged to
two mercury atoms. The compound series was characterized by low-temperature
single-crystal X-ray diffraction and low-temperature Raman spectroscopy. Several
structural motifs are observed within this structurally diverse series. These
include the infinite chain structures of the related compounds, 1 and 4; 2, a
dimeric structure which possesses an (HgO(MU))2 ring at its core; 3, a structure
based on a cage comprised of a (HgO(MU))3 ring that is capped on each face by
MU(3)-oxygen bridged F5TeO- groups; and 5, a dimeric structure possessing two
distorted (Hg3O2N) rings that are formally derived from 3 by replacement of a
F5TeO- group by a F2OSN- group in each ring. Quantum-chemical calculations were
carried out to gain insight into the bonding of the MU(3)-oxygen bridged teflate
groups observed in structure 3. Compounds 1-5 represent a novel class of neutral
transition metal complexes with NSF3, providing the first examples of NSF3
coordination to mercury. Compounds 4 and 5 also provide the only examples of
F2OSN- derivatives of mercury that have been characterized by single-crystal X
ray diffraction.
PMID- 26413857
TI - Curvature Softening and Negative Compressibility of Gel-Phase Lipid Membranes.
AB - We show that gel-phase lipid membranes soften upon bending, leading to curvature
localization and a negative compressibility. Using simulations of two very
different lipid models to quantify shape and stress-strain relation of buckled
membranes, we demonstrate that gel phase bilayers do not behave like Euler
elastica and hence are not well described by a quadratic Helfrich Hamiltonian,
much unlike their fluid-phase counterparts. We propose a theoretical framework
which accounts for the observed softening through an energy density that smoothly
crosses over from a quadratic to a linear curvature dependence beyond a critical
new scale [Formula: see text](-1). This model captures both the shape and the
stress-strain relation for our two sets of simulations and permits the extraction
of bending moduli, which are found to be about an order of magnitude larger than
the corresponding fluid phase values. We also find surprisingly large crossover
lengths [Formula: see text], several times bigger than the bilayer thickness,
rendering the exotic elasticity of gel-phase membranes more strongly pronounced
than that of homogeneous compressible sheets and artificial metamaterials. We
suggest that such membranes have unexpected potential as nanoscale systems with
striking materials characteristics.
PMID- 26413856
TI - Contribution of Raman spectroscopy in nephrology: a candidate technique to detect
hydroxyethyl starch of third generation in osmotic renal lesions.
AB - BACKGROUND AND OBJECTIVES: HydroxyEthyl Starch (HES) has been one of the most
commonly used colloid volume expanders in intensive care units for over 50 years.
The first and second generation HES, with a high molecular weight (>=200 kD) and
a high degree of substitution (>=0.5), has been associated with both renal
dysfunction and osmotic nephrosis-like lesions in histological studies. Recently,
third generation HES (130 kD/<0.5) has also been shown to impair renal function
in critically ill adult patients although tubular accumulation of HES has never
been proven in the human kidney. Our objective was to demonstrate the potential
of Raman micro-imaging to bring out the presence of third generation-HES in the
kidney of patients having received the volume expander. DESIGN: Four biopsies
presenting osmotic nephrosis-like lesions originated from HES-administrated
patients with impaired renal function were compared with HES-negative biopsies (n
= 10) by Raman microspectroscopy. RESULTS: The first step was dedicated to the
identification of a specific vibration of HES permitting the detection of the
cellular and tissue accumulation of the product. This specific vibration at 480
cm(-1) is assigned to a collective mode of the macromolecule; it is located in a
spectral region with a limited contribution from biological materials. Based on
this finding, HES distribution within tissue sections was investigated using
Raman micro-imaging. Determination of HES positive pixels permitted us to clearly
distinguish positive cases from HES-free biopsies (proportions of positive pixels
from the total number of pixels: 23.48% +/- 28 vs. 0.87% +/- 1.2; p = 0.004).
CONCLUSIONS: This study shows that Raman spectroscopy is a candidate technique to
detect HES in kidney tissue samples currently manipulated in nephrology
departments. In addition, on the clinical aspect, our approach suggests that
renal impairment related to third generation HES administration is associated
with osmotic nephrosis-like lesions and HES accumulation in the kidney.
PMID- 26413858
TI - A Hybrid One-Way ANOVA Approach for the Robust and Efficient Estimation of
Differential Gene Expression with Multiple Patterns.
AB - BACKGROUND: Identifying genes that are differentially expressed (DE) between two
or more conditions with multiple patterns of expression is one of the primary
objectives of gene expression data analysis. Several statistical approaches,
including one-way analysis of variance (ANOVA), are used to identify DE genes.
However, most of these methods provide misleading results for two or more
conditions with multiple patterns of expression in the presence of outlying
genes. In this paper, an attempt is made to develop a hybrid one-way ANOVA
approach that unifies the robustness and efficiency of estimation using the
minimum beta-divergence method to overcome some problems that arise in the
existing robust methods for both small- and large-sample cases with multiple
patterns of expression. RESULTS: The proposed method relies on a beta-weight
function, which produces values between 0 and 1. The beta-weight function with
beta = 0.2 is used as a measure of outlier detection. It assigns smaller weights
(>= 0) to outlying expressions and larger weights (<= 1) to typical expressions.
The distribution of the beta-weights is used to calculate the cut-off point,
which is compared to the observed beta-weight of an expression to determine
whether that gene expression is an outlier. This weight function plays a key role
in unifying the robustness and efficiency of estimation in one-way ANOVA.
CONCLUSION: Analyses of simulated gene expression profiles revealed that all
eight methods (ANOVA, SAM, LIMMA, EBarrays, eLNN, KW, robust BetaEB and proposed)
perform almost identically for m = 2 conditions in the absence of outliers.
However, the robust BetaEB method and the proposed method exhibited considerably
better performance than the other six methods in the presence of outliers. In
this case, the BetaEB method exhibited slightly better performance than the
proposed method for the small-sample cases, but the the proposed method exhibited
much better performance than the BetaEB method for both the small- and large
sample cases in the presence of more than 50% outlying genes. The proposed method
also exhibited better performance than the other methods for m > 2 conditions
with multiple patterns of expression, where the BetaEB was not extended for this
condition. Therefore, the proposed approach would be more suitable and reliable
on average for the identification of DE genes between two or more conditions with
multiple patterns of expression.
PMID- 26413859
TI - 'I am a mother': young women's negotiation of femininity and risk in the
transition to adulthood.
AB - In studies of sexual risk behaviour among youth, the role of dominant conceptions
of masculinity and femininity has received increasing attention. However, where
research has sought to explore femininity, it has predominantly focused on
adolescent girls. This paper departs from previous research by offering insights
into how young women negotiate their femininity as they transition from
adolescence to adulthood and encounter changing social contexts. Drawing on data
from ethnographic enquiry, it argues that as young women transition out of school
and into emerging adulthood, their options for negotiating different types of
femininity become constrained, with consequences for engagement in sexual risk
behaviours. This may to some extent explain why in some South African contexts
older young women are more vulnerable to HIV infection than adolescent girls. The
paper offer insights into future prospects for youth development programming
seeking to reduce young women's vulnerability to risk.
PMID- 26413861
TI - Alterations of Nonconserved Residues Affect Protein Stability and Folding
Dynamics through Charge-Charge Interactions.
AB - Charge-charge interactions play an important role in thermal stability of
proteins. We employed an all-atom, native-topology-based model with non-native
electrostatics to explore the interplay between folding dynamics and stability of
TNfn3 (the third fibronectin type III domain from tenascin-C). Our study
elucidates the role of charge-charge interactions in modulating the folding
energy landscape. In particular, we found that incorporation of explicit charge
charge interactions in the WT TNfn3 induces energetic frustration due to the
presence of residual structure in the unfolded state. Moreover, optimization of
the surface charge-charge interactions by altering the evolutionarily
nonconserved residues not only increases the thermal stability (in agreement with
previous experimental study) but also reduces the formation of residual structure
and hence minimizes the energetic frustration along the folding route. We
concluded that charge-charge interaction in the rationally designed TNfn3 plays
an important role not only in enhancing the stability but also in assisting
folding.
PMID- 26413860
TI - Chronic inflammation and risk of colorectal and other obesity-related cancers:
The health, aging and body composition study.
AB - Evidence of the association between chronic inflammation and the risk of
colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains
inconsistent, possibly due to a paucity of studies examining repeated measures of
inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79
years at baseline, we assessed whether circulating levels of three markers of
systemic inflammation, IL-6, CRP and TNF-alpha, were associated with the risk of
CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and
endometrium. Inflammatory markers were measured in stored fasting blood samples.
While only baseline measures of TNF-alpha were available, IL-6 and CRP were
additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit
to determine whether tertiles and log-transformed baseline, updated and averaged
measures of CRP and IL-6 and baseline measures of TNF-alpha were associated with
the risk of incident cancer(s). During a median follow-up of 11.9 years, we
observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the
highest tertile of updated CRP was more than double that in the lowest tertile
(HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between
colorectal cancer and IL-6 or TNF-alpha. Additionally, no significant
associations were found between obesity-related cancers and the three
inflammatory markers overall, but we observed a suggestion of effect modification
by BMI and NSAID use. In summary, in this population, higher CRP levels were
associated with increased risk of CRC, but not of OBRC. The findings provide new
evidence that chronically elevated levels of CRP, as reflected by repeated
measures of this marker, may play a role in colorectal carcinogenesis in older
adults.
PMID- 26413862
TI - Diversity in Compartmental Dynamics of Gene Regulatory Networks: The Immune
Response in Primary Influenza A Infection in Mice.
AB - Current approaches to study transcriptional profiles post influenza infection
typically rely on tissue sampling from one or two sites at a few time points,
such as spleen and lung in murine models. In this study, we infected female
C57/BL6 mice intranasally with mouse-adapted H3N2/Hong Kong/X31 avian influenza A
virus, and then analyzed the gene expression profiles in four different
compartments (blood, lung, mediastinal lymph nodes, and spleen) over 11
consecutive days post infection. These data were analyzed by an advanced
statistical procedure based on ordinary differential equation (ODE) modeling.
Vastly different lists of significant genes were identified by the same
statistical procedure in each compartment. Only 11 of them are significant in all
four compartments. We classified significant genes in each compartment into co
expressed modules based on temporal expression patterns. We then performed
functional enrichment analysis on these co-expression modules and identified
significant pathway and functional motifs. Finally, we used an ODE based model to
reconstruct gene regulatory network (GRN) for each compartment and studied their
network properties.
PMID- 26413863
TI - Laser Photocoagulation Induces Transduction of Retinal Pigment Epithelial Cells
by Intravitreally Administered Adeno-Associated Viral Vectors.
AB - Retinal transduction by intravitreally administered adeno-associated viral (AAV)
vector is previously known to be extremely limited to the neural retina except
AAV2 capsid type. Recently, we showed that prior laser photocoagulation enhances
retinal transduction of intravitreally administered AAV vectors, including the
outer retina and retinal pigment epithelium (RPE). Here, by performing short
pulse laser pretreatment on the mouse retina, we demonstrate RPE cells transduced
by three different capsid types of AAV vectors, AAV2, AAV5, and AAV8, using RPE
wholemounts. For all capsid types, laser pretreatment effectively induced the
transduction of RPE cells in and around the laser site.
PMID- 26413864
TI - Comparison of the effect of two Quillaja bark saponin extracts on DPPC and
DPPC/cholesterol Langmuir monolayers.
AB - The present study aims at comparing the effect of two commercially available
Quillaja bark saponin (QBS) products on model Langmuir monolayers. Pure
dipalmitoylphosphatidylcholine (DPPC) and mixed DPPC/cholesterol Langmuir
monolayers were used as crude models of erythrocyte membranes in order to better
understand a hemolytic activity of QBS. Both QBS products are mixtures of several
saponins and non-saponin fractions, only few of which can be assigned an exact
chemical structure, as shown by an HPLC analysis. Noticeable differences in the
saponin profiles, and most importantly-in the content of non-saponin fractions
(tannins and phenolic compounds) are probably responsible for their different
adsorption behavior at the water/air interface. The lipids Langmuir monolayers
were initially spread on pure water and compressed to surface pressure of 32.5
mN/m, which is believed to provide the lipid packing similar to that in real
biological membranes. The water subphase was subsequently exchanged with the
respective QBS solutions in the concentration range 5 * 10(-4) to 2 * 10(-1)wt%.
In order to assess the resistance of the model lipid monolayers to QBS, a
combination of surface pressure relaxation and surface dilatational rheology was
employed. Both QBS are shown to penetrate the lipid layers without removing them,
but their effect on the lipid layers' relaxation and viscoelastic dilational
properties is different. The differences virtually disappear when cholesterol is
present in the monolayer, especially for the DPPC/Cholesterol molar ratio between
10:9 and 4:1 (mol/mol). Despite several jumps of surface pressure, the lipid
layers containing cholesterol can resist penetration of QBS.
PMID- 26413865
TI - Magnesium oxide nanoparticles coated with glucose can silence important genes of
Leishmania major at sub-toxic concentrations.
AB - The aim of this study was to investigate the effect of magnesium oxide
nanoparticles (MgO NPs) and MgO NPs coated with glucose (MONPCG) on Leishmania
(L) major. First, the promastigotes of L. major were separately incubated with
serial concentrations of MgO NPs and MONPCG for 24, 48, and 72 h at 37 degrees
C. Then, the cell viability of promastigotes was evaluated by MTT assay. On the
other hand, the relative expression of Cpb and GP63 genes was detected by
quantitative-real time PCR. Based on results, the increase of concentration, both
MgO NPs and MONPCG, and incubation time led to decrease of cell viability.
Moreover, the expression of Cpb and GP63 genes was decreased with increase of
concentration of MgO NPs and MONPCG. Also, the increase of incubation time led to
decrease of their expression in MgO NPs treated promastogotes. But, in case of
MONPCG treated promastogotes, the increase of incubation time did not change the
expression of Cpb and GP63. Interestingly, MONPCG could silence Cpb and GP63
genes better than MgO NPs. Note, the capability was also seen at sub-toxic
concentrations of MONPCG.
PMID- 26413866
TI - Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a
Multiplexed Droplet Digital PCR Approach.
AB - Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in
oncogene-driven lung cancer. The range of KRAS point mutations observed in NSCLC
necessitates a multiplex approach to efficient mutation detection in circulating
DNA. Here we report the design and optimisation of three discriminatory ddPCR
multiplex assays investigating nine different KRAS mutations using PrimePCRTM
ddPCRTM Mutation Assays and the Bio-Rad QX100 system. Together these mutations
account for 95% of the nucleotide changes found in KRAS in human cancer.
Multiplex reactions were optimised on genomic DNA extracted from KRAS mutant cell
lines and tested on DNA extracted from fixed tumour tissue from a cohort of lung
cancer patients without prior knowledge of the specific KRAS genotype. The
multiplex ddPCR assays had a limit of detection of better than 1 mutant KRAS
molecule in 2,000 wild-type KRAS molecules, which compared favourably with a
limit of detection of 1 in 50 for next generation sequencing and 1 in 10 for
Sanger sequencing. Multiplex ddPCR assays thus provide a highly efficient
methodology to identify KRAS mutations in lung adenocarcinoma.
PMID- 26413867
TI - Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis.
AB - Alterations in insulin granule exocytosis and endocytosis are paramount to
pancreatic beta cell dysfunction in diabetes mellitus. Here, using temporally
controlled gene ablation specifically in beta cells in mice, we identified an
essential role of dynamin 2 GTPase in preserving normal biphasic insulin
secretion and blood glucose homeostasis. Dynamin 2 deletion in beta cells caused
glucose intolerance and substantial reduction of the second phase of glucose
stimulated insulin secretion (GSIS); however, mutant beta cells still maintained
abundant insulin granules, with no signs of cell surface expansion. Compared with
control beta cells, real-time capacitance measurements demonstrated that
exocytosis-endocytosis coupling was less efficient but not abolished; clathrin
mediated endocytosis (CME) was severely impaired at the step of membrane fission,
which resulted in accumulation of clathrin-coated endocytic intermediates on the
plasma membrane. Moreover, dynamin 2 ablation in beta cells led to striking
reorganization and enhancement of actin filaments, and insulin granule
recruitment and mobilization were impaired at the later stage of GSIS. Together,
our results demonstrate that dynamin 2 regulates insulin secretory capacity and
dynamics in vivo through a mechanism depending on CME and F-actin remodeling.
Moreover, this study indicates a potential pathophysiological link between
endocytosis and diabetes mellitus.
PMID- 26413868
TI - Dual-Affinity Re-Targeting proteins direct T cell-mediated cytolysis of latently
HIV-infected cells.
AB - Enhancement of HIV-specific immunity is likely required to eliminate latent HIV
infection. Here, we have developed an immunotherapeutic modality aimed to improve
T cell-mediated clearance of HIV-1-infected cells. Specifically, we employed Dual
Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based
molecules that can bind 2 distinct cell-surface molecules simultaneously. We
designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm that
was derived from broadly binding, antibody-dependent cellular cytotoxicity
mediating antibodies known to bind to HIV-infected target cells coupled to a
monovalent CD3 binding arm designed to engage cytolytic effector T cells
(referred to as HIVxCD3 DARTs). Thus, these DARTs redirected polyclonal T cells
to specifically engage with and kill Env-expressing cells, including CD4+ T cells
infected with different HIV-1 subtypes, thereby obviating the requirement for HIV
specific immunity. Using lymphocytes from patients on suppressive antiretroviral
therapy (ART), we demonstrated that DARTs mediate CD8+ T cell clearance of CD4+ T
cells that are superinfected with the HIV-1 strain JR-CSF or infected with
autologous reservoir viruses isolated from HIV-infected-patient resting CD4+ T
cells. Moreover, DARTs mediated CD8+ T cell clearance of HIV from resting CD4+ T
cell cultures following induction of latent virus expression. Combined with HIV
latency reversing agents, HIVxCD3 DARTs have the potential to be effective
immunotherapeutic agents to clear latent HIV-1 reservoirs in HIV-infected
individuals.
PMID- 26413869
TI - LKB1 loss promotes endometrial cancer progression via CCL2-dependent macrophage
recruitment.
AB - Endometrial cancer is the most common gynecologic malignancy and the fourth most
common malignancy in women. For most patients in whom the disease is confined to
the uterus, treatment results in successful remission; however, there are no
curative treatments for tumors that have progressed beyond the uterus. The
serine/threonine kinase LKB1 has been identified as a potent suppressor of
uterine cancer, but the biological modes of action of LKB1 in this context remain
incompletely understood. Here, we have shown that LKB1 suppresses tumor
progression by altering gene expression in the tumor microenvironment. We
determined that LKB1 inactivation results in abnormal, cell-autonomous production
of the inflammatory cytokine chemokine (C-C motif) ligand 2 (CCL2) within tumors,
which leads to increased recruitment of macrophages with prominent tumor
promoting activities. Inactivation of Ccl2 in an Lkb1-driven mouse model of
endometrial cancer slowed tumor progression and increased survival. In human
primary endometrial cancers, loss of LKB1 protein was strongly associated with
increased CCL2 expression by tumor cells as well as increased macrophage density
in the tumor microenvironment. These data demonstrate that CCL2 is a potent
effector of LKB1 loss in endometrial cancer, creating potential avenues for
therapeutic opportunities.
PMID- 26413870
TI - Excess placental secreted frizzled-related protein 1 in maternal smokers impairs
fetal growth.
AB - Maternal cigarette smoking during pregnancy remains one of the most common and
preventable causes of fetal growth restriction (FGR), a condition in which a
fetus is unable to achieve its genetically determined potential size. Even though
epidemiologic evidence clearly links maternal cigarette smoking with FGR, insight
into the molecular mechanisms of cigarette smoke-induced FGR is lacking. Here, we
performed transcriptional profiling of placentas obtained from smoking mothers
who delivered growth-restricted infants and identified secreted frizzled-related
protein 1 (sFRP1), an extracellular antagonist of endogenous WNT signaling, as a
candidate molecule. sFRP1 mRNA and protein levels were markedly upregulated (~10
fold) in placentas from smoking mothers compared with those from nonsmokers. In
pregnant mice, adenovirus-mediated overexpression of sFRP1 led to FGR, increased
karyorrhexis in the junctional zone, and decreased proliferation of labyrinthine
trophoblasts. Consistent with our hypothesis that placental WNT signaling is
suppressed in maternal smokers, we found that exposure to carbon monoxide analogs
led to reduced WNT signaling, increased SFRP1 mRNA expression, and decreased
cellular proliferation in a trophoblast cell line. Moreover, administration of
carbon monoxide analogs to pregnant mice in late gestation led to FGR. In
summary, our results indicate that the increased placental expression of sFRP1
seen in smokers impairs fetal growth by inhibiting WNT signaling and trophoblast
proliferation.
PMID- 26413871
TI - IL-21R signaling is critical for induction of spontaneous experimental autoimmune
encephalomyelitis.
AB - IL-17-producing CD4+ T cells (Th17 cells) have well-described pathogenic roles in
tissue inflammation and autoimmune diseases, such as experimental autoimmune
encephalomyelitis (EAE); however, the involvement of IL-21 in these processes has
remained controversial. While IL-21 is an essential autocrine amplification
factor for differentiation of Th17 cells, the loss of IL-21 or IL-21 receptor (IL
21R) does not protect mice from actively induced EAE. Here, we utilized a
transgenic EAE mouse model, in which T and B cells overexpress receptors for
myelin oligodendrocyte glycoprotein (MOG) (referred to as 2D2xTH mice), and
demonstrated that IL-21 is critical for the development of a variant form of
spontaneous EAE in these animals. Il21r deletion in 2D2xTH mice reduced the
incidence and severity of spontaneous EAE, which was associated with a defect in
Th17 cell generation. Moreover, IL-21R deficiency limited IL-23R expression on
Th17 cells and inhibited expression of key molecules involved in the generation
of pathogenic Th17 cells. Conversely, loss of IL-23R in 2D2xTH mice resulted in
complete resistance to the development of spontaneous EAE. Our data identify a
previously unappreciated role for IL-21 in EAE and reveal that IL-21-mediated
signaling supports generation and stabilization of pathogenic Th17 cells and
development of spontaneous autoimmunity.
PMID- 26413872
TI - TIGIT predominantly regulates the immune response via regulatory T cells.
AB - Coinhibitory receptors are critical for the maintenance of immune homeostasis.
Upregulation of these receptors on effector T cells terminates T cell responses,
while their expression on Tregs promotes their suppressor function. Understanding
the function of coinhibitory receptors in effector T cells and Tregs is crucial,
as therapies that target coinhibitory receptors are currently at the forefront of
treatment strategies for cancer and other chronic diseases. T cell Ig and ITIM
domain (TIGIT) is a recently identified coinhibitory receptor that is found on
the surface of a variety of lymphoid cells, and its role in immune regulation is
just beginning to be elucidated. We examined TIGIT-mediated immune regulation in
different murine cancer models and determined that TIGIT marks the most
dysfunctional subset of CD8+ T cells in tumor tissue as well as tumor-tissue
Tregs with a highly active and suppressive phenotype. We demonstrated that TIGIT
signaling in Tregs directs their phenotype and that TIGIT primarily suppresses
antitumor immunity via Tregs and not CD8+ T cells. Moreover, TIGIT+ Tregs
upregulated expression of the coinhibitory receptor TIM-3 in tumor tissue, and
TIM-3 and TIGIT synergized to suppress antitumor immune responses. Our findings
provide mechanistic insight into how TIGIT regulates immune responses in chronic
disease settings.
PMID- 26413873
TI - A Pilot Study of IL2 in Drug-Resistant Idiopathic Nephrotic Syndrome.
AB - Tregs infusion reverts proteinuria and reduces renal lesions in most animal
models of nephrotic syndrome (i.e. Buffalo/Mna, Adriamycin, Promycin, LPS). IL2
up-regulates Tregs and may be an alternative to cell-therapy in this setting. To
evaluate a potential role of IL2 as Tregs inducer and proteinuria lowering agent
in human nephrotic syndrome we treated 5 nephrotic patients with 6 monthly cycles
of low-dose IL2 (1x106 U/m2 first month, 1.5x106 U/m2 following months). The
study cohort consisted of 5 children (all boys, 11-17 years) resistant to all the
available treatments (i.e. steroids, calcineurin inhibitors, mycophenolate,
Rituximab). Participants had Focal Segmental Glomerulosclerosis (3 cases) or
Minimal Change Nephropathy (2 cases). IL2 was safe in all but one patient who had
an acute asthma attack after the first IL2 dose and did not receive further
doses. Circulating Tregs were stably increased (>10%) during the whole study
period in 2 cases while were only partially modified in the other two children
who started with very low levels and partially responded to single IL2
Proteinuria and renal function were not modified by IL2 at any phase of the
study. We concluded that low-dose IL2 given in monthly pulses is safe and
modifies the levels of circulating Tregs. This drug may not be able to lower
proteinuria or affect renal function in children with idiopathic nephrotic
syndrome. We were unable to reproduce in humans the effects of IL2 described in
rats and mice reducing de facto the interest on this drug in nephrotic syndrome.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02455908.
PMID- 26413874
TI - Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation
membrane during selective autophagy.
AB - Autophagy is a major pathway for the clearance of harmful material from the
cytoplasm. During autophagy, cytoplasmic material is delivered into the lysosomal
system by organelles called autophagosomes. Autophagosomes form in a de novo
manner and, in the course of their formation, isolate cargo material from the
rest of the cytoplasm. Cargo specificity is conferred by autophagic cargo
receptors that selectively link the cargo to the autophagosomal membrane
decorated with ATG8 family proteins such as LC3B. Here we show that the human
cargo receptor p62/SQSTM-1 employs oligomerization to stabilize its interaction
with LC3B and linear ubiquitin when they are clustered on surfaces. Thus,
oligomerization enables p62 to simultaneously select for the isolation membrane
and the ubiquitinated cargo. We further show in a fully reconstituted system that
the interaction of p62 with ubiquitin and LC3B is sufficient to bend the membrane
around the cargo.
PMID- 26413875
TI - Ultrasonographic Identification of the Anterolateral Ligament of the Knee.
AB - PURPOSE: To determine ultrasonography's sensitivity for identifying the
anterolateral ligament (ALL). METHODS: A descriptive study of 18 cadaveric knees
was performed. Ultrasonography was used to locate any anterolateral structures at
the knee that could correspond to the ALL. The structure's length and relation
with other notable anatomic landmarks (fibular head, Gerdy tubercle, joint line,
lateral femoral epicondyle, popliteus tendon insertion) were quantified. The
ultrasonography measurements were validated by dissecting each knee. The
sensitivity of ultrasonography for detecting the ALL and the agreement between
the ultrasonographic and cadaveric measurements (Cohen kappa) were determined by
statistical analysis. RESULTS: The ALL was found in all 18 cadaveric knees and
corresponded anatomically to the ultrasonographic descriptions. Ultrasonography
had 100% sensitivity for detecting the presence of the ALL. The ALL's insertion
on the lateral femoral condyle was, on average, 12.08 mm (SD, 4 mm; range, 7 to
15 mm) proximal and posterior to the lateral femoral epicondyle and 20.5 mm (SD,
3 mm; range, 16 to 24 mm) proximal to the middle of the popliteus tendon
insertion. The ALL inserted onto the tibia, midway between the Gerdy tubercle and
the fibular head; the distance between the midpoint of the tibial insertion and
middle of the Gerdy tubercle was 19.05 mm (SD, 2.1 mm; range, 15 to 25 mm), and
the distance was 19.13 mm (SD, 2.3 mm; range, 14 to 23 mm) to the tip of the
fibular head. The agreement between the ultrasonographic and cadaveric findings
was excellent (Cohen kappa coefficient between 0.88 and 0.94). CONCLUSIONS:
Ultrasound imaging is a suitable tool for identifying the ALL of the knee, and it
allowed for a detailed analysis of the entire ALL in all 18 knees. However, its
ability to evaluate any injuries to the ALL must still be shown. CLINICAL
RELEVANCE: Ultrasonography can be used to confirm the integrity of the ALL.
PMID- 26413877
TI - A Not-So-Subtle Bump on the Head.
PMID- 26413876
TI - Preferential Extracellular Generation of the Active Parkinsonian Toxin MPP+ by
Transporter-Independent Export of the Intermediate MPDP+.
AB - AIMS: 1-Methyl-4-phenyl-tetrahydropyridine (MPTP) is among the most widely used
neurotoxins for inducing experimental parkinsonism. MPTP causes parkinsonian
symptoms in mice, primates, and humans by killing a subpopulation of dopaminergic
neurons. Extrapolations of data obtained using MPTP-based parkinsonism models to
human disease are common; however, the precise mechanism by which MPTP is
converted into its active neurotoxic metabolite, 1-methyl-4-phenyl-pyridinium
(MPP(+)), has not been fully elucidated. In this study, we aimed to address two
unanswered questions related to MPTP toxicology: (1) Why are MPTP-converting
astrocytes largely spared from toxicity? (2) How does MPP(+) reach the
extracellular space? RESULTS: In MPTP-treated astrocytes, we discovered that the
membrane-impermeable MPP(+), which is generally assumed to be formed inside
astrocytes, is almost exclusively detected outside of these cells. Instead of a
transporter-mediated export, we found that the intermediate, 1-methyl-4-phenyl
2,3-dihydropyridinium (MPDP(+)), and/or its uncharged conjugate base passively
diffused across cell membranes and that MPP(+) was formed predominately by the
extracellular oxidation of MPDP(+) into MPP(+). This nonenzymatic extracellular
conversion of MPDP(+) was promoted by O2, a more alkaline pH, and dopamine
autoxidation products. INNOVATION AND CONCLUSION: Our data indicate that MPTP
metabolism is compartmentalized between intracellular and extracellular
environments, explain the absence of toxicity in MPTP-converting astrocytes, and
provide a rationale for the preferential formation of MPP(+) in the extracellular
space. The mechanism of transporter-independent extracellular MPP(+) formation
described here indicates that extracellular genesis of MPP(+) from MPDP is a
necessary prerequisite for the selective uptake of this toxin by
catecholaminergic neurons.
PMID- 26413878
TI - A cholesterol-lowering VLP vaccine that targets PCSK9.
AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory protein that
controls cholesterol homeostasis by enhancing endosomal and lysosomal degradation
of the low-density lipoprotein receptor (LDL-R). Mutations that cause increased
activity of PCSK9 are associated with hypercholesterolemia, atherosclerosis and
early cardiovascular disease (CVD), whereas individuals with loss-of-function
mutations in PCSK9 are apparently healthy but are hypocholesterolemic and have a
dramatically decreased risk of CVD. In this study, we generated virus-like
particle (VLP)-based vaccines targeting PCSK9. Mice and macaques vaccinated with
bacteriophage VLPs displaying PCSK9-derived peptides developed high titer IgG
antibodies that bound to circulating PCSK9. Vaccination was associated with
significant reductions in total cholesterol, free cholesterol, phospholipids, and
triglycerides. A vaccine targeting PCSK9 may, therefore, be an attractive
alternative to monoclonal antibody-based therapies.
PMID- 26413879
TI - A systematic review of adverse events following immunization during pregnancy and
the newborn period.
AB - In 2013, the WHO Strategic Advisory Group of Experts on Immunization (SAGE)
requested WHO to develop a process and a plan to move the maternal immunization
agenda forward in support of an increased alignment of data safety evidence,
public health needs, and regulatory processes. A key challenge identified was the
continued need for harmonization of maternal adverse event following immunization
(AEFI) research and surveillance efforts within developing and developed country
contexts. We conducted a systematic review as a preliminary step in the
development of standardized AEFI definitions for use in maternal and neonatal
clinical trials, post-licensure surveillance, and other vaccine studies. We
documented the current extent and nature of variability in AEFI definitions and
adverse event reporting among 74 maternal immunization studies, which reported a
total of 240 different types of adverse events. Forty-nine studies provided
explicit AEFI case definitions describing 35 separate types of AEFIs. We
identified variability in how AEFIs were determined to be present, in how AEFI
definitions were applied, and in the ways that AEFIs were reported. Definitions
for key maternal/neonatal AEFIs differed on four discrete attributes: overall
level of detail, physiological and temporal boundaries and cut-offs, severity
strata, and standards used. Our findings suggest that investigators may
proactively address these inconsistencies through comprehensive and consistent
reporting of AEFI definitions and outcomes in future publications. In addition,
efforts to develop standardized AEFI definitions should generate definitions of
sufficient detail and consistency of language to avoid the ambiguities we
identified in reviewed articles, while remaining practically applicable given the
constraints of low-resource contexts such as limited diagnostic capacity and high
patient throughput.
PMID- 26413880
TI - Antigen-specific IgA titres after 23-valent pneumococcal vaccine indicate
transient antibody deficiency disease in children.
AB - Paediatric patients with antibody deficiency may either be delayed in development
of humoral immunity or may be persistently deficient in antibody production. To
differentiate between these entities, we examined the 23-valent pneumococcal
polysaccharide (PnPS) vaccine-induced IgM-, IgG- and IgA antibody responses in a
cohort of 66 children with recurrent respiratory tract infections. Individual
serum titres against 11 pneumococcal serotypes were measured by Luminex. The
cohort contained 33 antibody deficiency patients, 17 transient antibody
deficiency patients and 16 patients without antibody deficiency diagnosis
(control group). Transient antibody deficiency patients produced consistently
higher levels of PnPS-specific IgA responses than antibody deficiency patients.
Decreased IgA responses to serotypes 1, 5, 7F and 18C were most discriminative to
stratify transient antibody deficiency patients from antibody deficiency patients
with persistent disease. We conclude that measuring PnPS-specific IgA responses
may predict the disease course in young children diagnosed with antibody
deficiency and suggest confirmation of these data in a prospective setting.
PMID- 26413881
TI - Will there ever be a new influenza pandemic and are we prepared?
PMID- 26413882
TI - Isometrically invariant and allosterically aware description of deformable
macromolecular surfaces: Application to the viral neuraminidase.
AB - MOTIVATION: The macromolecular surfaces associated with proteins and
macromolecules play a key role in determining their functionality and
interactions, and are also of importance in structural analysis and
classification. As a result of their interaction with their environment, the
macromolecular surfaces experience random conformational deformations.
Consequently, a realistic description of the molecular surface must be invariant
under these deformations. Further, the motion associated with disconnected
regions on the molecular surface may be correlated. This property is known as the
allosteric effect. In this paper, we address these two requirements. To this end,
we propose an approach based on discrete differential geometry and the fractional
Fokker-Planck equation which provides an isometrically invariant and allosteric
aware description of macromolecular surfaces. Our method is applied to the
influenza neuraminidase.
PMID- 26413883
TI - Bone marrow microenvironmental CD4 + and CD8 + lymphocyte infiltration patterns
define overall- and progression free survival in standard risk multiple myeloma-
an analysis from the Austrian Myeloma Registry.
PMID- 26413884
TI - Anti-Aging and Tissue Regeneration Ability of Policosanol Along with Lipid
Lowering Effect in Hyperlipidemic Zebrafish via Enhancement of High-Density
Lipoprotein Functionality.
AB - We investigated the tissue regeneration and lipid-lowering effects of policosanol
(PCO) by employing a hyperlipidemic zebrafish model. A reconstituted high-density
lipoprotein containing policosanol (PCO-rHDL) facilitated greater cell growth and
replication with less apoptosis and reactive oxygen species (ROS) production in
BV-2 microglial cell lines. From in vivo study, injection of rHDL containing
apolipoprotein A-I (ApoA-I) caused 76 +/- 4% (p = 0.01) greater tissue
regeneration activity than the phosphate-buffered saline (PBS) control, whereas
PCO-rHDL caused 94 +/- 7% (p = 0.002) increased regeneration. PCO in ethanol
(EtOH) showed lower cholesteryl ester transfer protein (CETP) inhibitory ability
than did anacetrapib, whereas PCO-rHDL showed higher inhibitory ability than
anacetrapib, suggesting a synergistic effect between PCO and rHDL. Following 9
weeks of PCO consumption, the PCO group (0.003% PCO in Tetrabit) showed the
highest survivability (80%), whereas normal diet (ND) and high-cholesterol diet
(HCD) control groups showed 67% and 70% survival rates, respectively.
Supplementation with a HCD resulted in two-fold elevation of CETP activity along
with 3- and 2.5-fold increases in serum total cholesterol (TC) and triglycerides
(TGs) levels, respectively. Consumption of PCO for 9 weeks resulted in 40 +/- 5%
(p = 0.01 vs. HCD) and 33 +/- 4% (p = 0.02 vs. HCD) reduction of TC and TGs
levels, respectively. Serum high-density lipoprotein cholesterol (HDL-C) level
increased up to 37 +/- 2 mg/dL (p = 0.004), whereas the percentage of HDL-C/TC
increased up to 20 +/- 2% from 5 +/- 1% compared to the HCD control. The serum
glucose level was reduced to 47 +/- 2% (p = 0.002) compared to the HCD control.
Fatty liver change and hepatic inflammation levels were remarkably increased upon
HCD consumption and were two-fold higher than that under ND. However, the PCO
group showed 58 +/- 5% (p = 0.001) and 50 +/- 3% (p = 0.006) reduction of
inflammation enzyme levels and lipid content in hepatic tissue under HCD. In
conclusion, PCO supplementation showed lipid-lowering and HDL-C-elevating effects
with ameliorating fatty liver change. These in vivo anti-atherosclerotic and anti
diabetic effects of PCO are well associated with in vitro anti-apoptotic
activities.
PMID- 26413885
TI - A Single Dose of Intraoperative Antibiotics Is Sufficient to Prevent Urinary
Tract Infection During Ureteroscopy.
AB - BACKGROUND: American Urology Association (AUA) Best Practice Guidelines for
ureteroscopic stone treatment recommend antibiotic coverage for <24 hours
following the procedure. The purpose of this study was to evaluate if the
addition of postoperative antibiotics reduces urinary tract infections (UTIs)
following ureteroscopic stone treatment beyond the recommended preoperative dose.
METHODS: A retrospective review was performed of consecutive patients at two
institutions, University of British Columbia and Massachusetts General Hospital,
Harvard. All patients received a single dose of antibiotics before ureteroscopic
stone treatment. A subset of patients was also given postoperative antibiotics.
The rate of UTI was compared in patients receiving only preoperative antibiotics
(group 1) vs those who received pre- and postoperative antibiotics (group 2).
RESULTS: Eighty-one patients underwent ureteroscopy for renal calculi. Mean time
to follow up was 42 +/- 88 days. Eight (9.9%) patients in total (two from group 1
and six from group 2, p = 0.1457) developed UTIs postoperatively. In group 1,
both patients presented with pyelonephritis (n = 2); those patients with
infections in group 2 presented with urosepsis (n = 2) and cystitis (n = 2) and
two patients had asymptomatic bacteriuria. Risk factors such as preoperative
stenting, nephrostomy tubes, and foley catheters neither differed between groups
nor did they predispose patients to postoperative infections. CONCLUSIONS: The
postoperative UTI rate in this study (9.9%) is consistent with previous reports.
Our data suggest that a single preoperative dose of antibiotics is sufficient,
and additional postoperative antibiotics do not decrease infection rates after
ureteroscopic stone treatment. Risk for selection bias is a potential limitation.
PMID- 26413886
TI - Imbalance Between Bone Morphogenetic Protein 2 and Noggin Induces Abnormal
Osteogenic Differentiation of Mesenchymal Stem Cells in Ankylosing Spondylitis.
AB - OBJECTIVE: To study the osteogenic differentiation capacity of bone marrow
derived mesenchymal stem cells (BM-MSCs) from patients with ankylosing
spondylitis (AS) and to investigate the mechanisms of abnormal osteogenic
differentiation of BM-MSCs in AS. METHODS: BM-MSCs from healthy donors (HD-MSCs)
and patients with AS (AS-MSCs) were cultured in osteogenic differentiation medium
for 0-21 days, after which their osteogenic differentiation capacity was
determined using alizarin red S and alkaline phosphatase assays. Gene expression
levels of osteoblastic markers and related cytokines were detected by high
throughput quantitative reverse transcription-polymerase chain reaction. Enzyme
linked immunosorbent assay was performed to detect protein levels of bone
morphogenetic protein 2 (BMP-2) and Noggin in the cell culture supernatant. The
activation of Smad1/5/8 and MAPK signaling pathways was measured by Western
blotting. The balance between BMP-2 and Noggin expression was regulated using
lentiviruses encoding short hairpin RNA and exogenous Noggin, respectively, which
enabled evaluation of how this balance affected osteogenic differentiation of AS
MSCs. RESULTS: AS-MSCs outperformed HD-MSCs in osteogenic differentiation
capacity. During osteogenic differentiation, AS-MSCs secreted more BMP-2 but less
Noggin, accompanied by an overactivation of Smad1/5/8 and ERK-1/2. When the
Noggin concentration was increased or BMP-2 expression was inhibited, the
abnormal osteogenic differentiation of AS-MSCs was rectified. In addition, the
balance between BMP-2 and Noggin secretion was restored. CONCLUSION: The results
of this study demonstrate that an imbalance between BMP-2 and Noggin secretion
induces abnormal osteogenic differentiation of AS-MSCs. These findings reveal a
mechanism of pathologic osteogenesis in AS and provide a new perspective on
inhibiting pathologic osteogenesis by regulating the balance between BMP-2 and
Noggin.
PMID- 26413887
TI - Characterization of Streptomycin Resistance in Isolates of Erwinia amylovora in
California.
AB - In surveys from 2006 to 2014, streptomycin resistance in Erwinia amylovora from
pear-growing areas in California declined from very high incidence in 2006 and
2007 to very low incidence in 2013 and 2014. The majority of resistant strains
were designated as moderately resistant-low (MR-L), and were almost exclusively
found in Sacramento County, whereas highly resistant (HR) strains were only
recovered in Sutter-Yuba and San Joaquin counties. Resistance of HR strains was
associated with a mutation in codon 43 of the chromosomal rpsL gene that results
in a change from lysine to arginine, the same mutation that was originally
reported for resistant strains from California in the mid-1970s. MR-L strains
were found to harbor the strA-strB streptomycin resistance genes on transposon
Tn5393a. This transposon lacks insertion sequence IS1133 that provides a promoter
for efficient expression of strA-strB, resulting in lower minimum inhibitory
concentrations of MR-L strains compared with those from other locations that
harbor strA-strB on Tn5393::IS1133. In contrast to previously described plasmid
mediated resistance where Tn5393 is inserted in pEa34, or pEA29, Tn5393a in MR-L
strains was located on plasmid pEU30. This plasmid was first described in E.
amylovora from the western United States but was not associated with streptomycin
resistance determinants previously. We hypothesize that Tn5393a was introduced
into an E. amylovora strain carrying pEU30 and transposed into that plasmid. This
hypothesis was supported by clustered regularly interspaced short palindromic
repeat (CRISPR) sequence analysis that showed that two MR-L strains share the
same CRISPR1 pattern as a streptomycin-sensitive strain. With current low
resistance levels in California growing regions, streptomycin could be
successfully used again, but applications per season should be limited and the
antibiotic should be mixed and rotated with different modes of action.
PMID- 26413888
TI - Why is number word learning hard? Evidence from bilingual learners.
AB - Young children typically take between 18 months and 2 years to learn the meanings
of number words. In the present study, we investigated this developmental
trajectory in bilingual preschoolers to examine the relative contributions of two
factors in number word learning: (1) the construction of numerical concepts, and
(2) the mapping of language specific words onto these concepts. We found that
children learn the meanings of small number words (i.e., one, two, and three)
independently in each language, indicating that observed delays in learning these
words are attributable to difficulties in mapping words to concepts. In contrast,
children generally learned to accurately count larger sets (i.e., five or
greater) simultaneously in their two languages, suggesting that the difficulty in
learning to count is not tied to a specific language. We also replicated previous
studies that found that children learn the counting procedure before they learn
its logic - i.e., that for any natural number, n, the successor of n in the count
list denotes the cardinality n+1. Consistent with past studies, we found that
children's knowledge of successors is first acquired incrementally. In
bilinguals, we found that this knowledge exhibits item-specific transfer between
languages, suggesting that the logic of the positive integers may not be stored
in a language-specific format. We conclude that delays in learning the meanings
of small number words are mainly due to language-specific processes of mapping
words to concepts, whereas the logic and procedures of counting appear to be
learned in a format that is independent of a particular language and thus
transfers rapidly from one language to the other in development.
PMID- 26413889
TI - The AINU Technique for Laparoscopic Vesico-Vaginal Fistula Repair: A Preliminary
Report.
AB - INTRODUCTION: With safe obstetric practices now globally available, most vesico
vaginal fistulas (VVF) presenting in recent times are secondary to various
gynecologic surgeries. Most of them are supra-trigonal in location. Laparoscopic
repair of VVF is gaining ground as an alternative to open repair of VVF. In this
study, we describe our initial experience with a novel technique of laparoscopic
VVF repair involving a limited transverse cystotomy for access and a single
layered barbed suture closure of bladder. MATERIALS AND METHODS: Twenty cases of
supra-trigonal VVFs following gynecologic surgeries were taken up for repair by
our novel technique. The mean age of the patients was 32 years and the mean VVF
size was 1.5 cm. RESULTS: The mean operative time was 54 min. Estimated mean
blood loss was 30 ml and the mean postoperative stay was 2.5 days. None of the
patients had any recurrence with a mean follow-up of 14 months. CONCLUSION: The
limited transverse cystotomy approach has advantages in decreasing the operative
time, improving ease of laparoscopic suturing, allowing an automatic separation
of suture lines and allowing for an easier anterior dissection of the bladder to
reduce tension on the suture line if necessary. Further this approach provides
excellent results in select patients of supra-trigonal VVF in terms of continence
and postoperative bladder overactivity.
PMID- 26413890
TI - Strategy use fully mediates the relationship between working memory capacity and
performance on Raven's matrices.
AB - Working memory capacity consistently correlates with fluid intelligence. It has
been suggested that this relationship is partly attributable to strategy use:
Participants with high working memory capacity would use more effective
strategies, in turn leading to higher performance on fluid intelligence tasks.
However, this idea has never been directly investigated. In 2 experiments, we
tested this hypothesis by directly manipulating strategy use in a combined
experimental-correlational approach (Experiment 1; N = 250) and by measuring
strategy use with a self-report questionnaire (Experiment 2; N = 93). Inducing
all participants to use an effective strategy in Raven's matrices decreased the
correlation between working memory capacity and performance; the strategy use
measure fully mediated the relationship between working memory capacity and
performance on the matrices task. These findings indicate that individual
differences in strategic behavior drive the predictive utility of working memory.
We interpret the results within a theoretical framework integrating the multiple
mediators of the relationship between working memory capacity and high-level
cognition.
PMID- 26413891
TI - Fast but not intuitive, slow but not reflective: Decision conflict drives
reaction times in social dilemmas.
AB - When people have the chance to help others at a cost to themselves, are
cooperative decisions driven by intuition or reflection? To answer this question,
recent studies have tested the relationship between reaction times (RTs) and
cooperation, reporting both positive and negative correlations. To reconcile this
apparent contradiction, we argue that decision conflict (rather than the use of
intuition vs. reflection) drives response times, leading to an inverted-U shaped
relationship between RT and cooperation. Studies 1 through 3 show that
intermediate decisions take longer than both extremely selfish and extremely
cooperative decisions. Studies 4 and 5 find that the conflict between self
interested and cooperative motives explains individual differences in RTs.
Manipulating conflictedness causes longer RTs and more intermediate decisions,
and RTs mediate the relationship between conflict and intermediate decisions.
Finally, Studies 6 and 7 demonstrate that conflict is distinct from reflection by
manipulating the use of intuition (vs. reflection). Experimentally promoting
reliance on intuition increases cooperation, but has no effects on decision
extremity or feelings of conflictedness. In sum, we provide evidence that RTs
should not be interpreted as a direct proxy for the use of intuitive or
reflective processes, and dissociate the effects of conflict and reflection in
social decision making.
PMID- 26413892
TI - Compete, coordinate, and cooperate: How to exploit uncertain environments with
social interaction.
AB - Countless decisions, from the trivial to the crucial, are made in complex social
contexts while facing uncertain consequences. Yet a large portion of decision
making research focuses on either the effects of social interaction or the
effects of environmental uncertainty by examining strategic games against others
or individual games against nature. Drawing a connection between these
approaches, the authors extend a standard individual choice paradigm to include
social interaction with 1 other person. In this paradigm, 2 competing decision
makers repeatedly select among 2 options, each offering a particular probability
of a fixed payoff. When both players choose the same, correct option, the payoff
is evenly split; when they choose different options, the player choosing the
correct option receives the full payoff. The addition of this social dimension
gives players an opportunity to fully exploit an uncertain environment via
cooperation: By consistently choosing opposite options, two players can exploit
the uncertain environment more effectively than a single player could. We present
2 experiments that manipulate environmental (Experiment 1) and social (Experiment
2) aspects of the paradigm. In Experiment 1, the outcome probabilities were
either known or unknown to participants; in Experiment 2, participants' attention
was drawn to individual or group gains by introducing either within- or between
group competition. Efficient cooperation did not emerge spontaneously in
Experiment 1. Instead, most people probability maximized, mirroring the behavior
observed in individual choice. By contrast, between--group competition in
Experiment 2 facilitated efficient-but not always equitable--exploitation of
uncertain environments. This work links the concepts of individual risky choice
and strategic decision making under both environmental and social uncertainty.
PMID- 26413893
TI - Self-enhancement diminished.
AB - Self-enhancement is a positive bias in self-perception, which may imply error.
However, conventional measures of self-enhancement are difference scores that do
not distinguish a positive bias from a self-enhancement error, that is, they fail
to identify those individuals who hold an irrationally or inaccurately positive
view of themselves. We propose 2 new measures to separate error from bias. In the
domain of personality judgment, we estimate a defensible bias and an enhancement
error from individuals' actual and perceived similarity with others. In the
domain of performance, we adapt a decision-theoretic framework to distinguish
those who falsely believe to be better than average from those who actually are
better. We illustrate the properties of these measures in 3 empirical studies and
computer simulations. Implausibly high majorities of people consider themselves
to be above average on various dimensions.
PMID- 26413895
TI - Sedation versus general anaesthesia for provision of dental treatment to patients
younger than 18 years.
AB - BACKGROUND: A significant proportion of children have caries requiring
restorations or extractions, and some of these children will not accept this
treatment under local anaesthetic. Historically this has been managed by the use
of a general anaesthetic in children; however, use of sedation may lead to
reduced morbidity and cost. The aim of this review was to compare the efficiency
of sedation versus general anaesthesia (GA) for provision of dental treatment to
children and adolescents younger than 18 years. This review was originally
published in 2009 and was updated in 2012 and again in 2015. OBJECTIVES: We will
evaluate morbidity and effectiveness of sedation versus GA for provision of
dental treatment to patients younger than 18 years. If data become available, we
will analyse the cost-effectiveness of different interventions. If data are not
available, we will obtain crude estimates of cost.Morbidity can be defined as 'an
undesired result or complication'. For the purposes of this review,
'postoperative morbidity' refers to undesired results or complications such as
nausea following a procedure, once the patient had been restored to consciousness
and could breathe unaided. 'Intraoperative morbidity' refers to any complications
that occur during the procedure that may necessitate action by the anaesthetist
or the sedationist, such as respiratory arrest. SEARCH METHODS: In this updated
review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL;
2015, Issue 7); MEDLINE Ovid SP (1950 to July 2015); EMBASE Ovid SP (1974 to July
2015); System for Information on Grey Literature in Europe (SIGLE) (1980 to
October July 2012); Latin American & Caribbean Health Sciences Literature
(LILACS) (1982 to July 2015); and Institute for Scientific Information (ISI) Web
of Science (1945 to July 2015).We also carried out handsearching of relevant
journals to July 2015. We imposed no language restriction. SELECTION CRITERIA: We
planned to include randomized controlled clinical trials that compared sedative
agents versus general anaesthesia in children and adolescents up to 18 years of
age undergoing dental treatment. We excluded complex surgical procedures and
pseudo-randomized trials. DATA COLLECTION AND ANALYSIS: Two review authors
assessed titles and abstracts for inclusion in the review. We recorded
information relevant to objectives and outcome measures by using a specially
designed 'data extraction form'. We will employ the Grades of Recommendation,
Assessment, Development and Evaluation Working Group (GRADE) approach to
interpret findings. MAIN RESULTS: In our original review, we identified 16
studies for potential inclusion after searching available databases and screening
titles and abstracts. After retrieving full-text studies, we found none to be
eligible. We identified no additional studies in the updated search of July 2012.
We identified two studies for possible inclusion in the updated search of July
2015; again we found these to be ineligible. AUTHORS' CONCLUSIONS: Randomized
controlled studies comparing use of dental general anaesthesia versus sedation
are needed to quantify differences such as morbidity and cost.
PMID- 26413894
TI - The Ca2+-Regulation of the Mitochondrial External NADPH Dehydrogenase in Plants
Is Controlled by Cytosolic pH.
AB - NADPH is a key reductant carrier that maintains internal redox and antioxidant
status, and that links biosynthetic, catabolic and signalling pathways. Plants
have a mitochondrial external NADPH oxidation pathway, which depends on Ca2+ and
pH in vitro, but concentrations of Ca2+ needed are not known. We have determined
the K0.5(Ca2+) of the external NADPH dehydrogenase from Solanum tuberosum
mitochondria and membranes of E. coli expressing Arabidopsis thaliana NDB1 over
the physiological pH range using O2 and decylubiquinone as electron acceptors.
The K0.5(Ca2+) of NADPH oxidation was generally higher than for NADH oxidation,
and unlike the latter, it depended on pH. At pH 7.5, K0.5(Ca2+) for NADPH
oxidation was high (~100 MUM), yet 20-fold lower K0.5(Ca2+) values were
determined at pH 6.8. Lower K0.5(Ca2+) values were observed with decylubiquinone
than with O2 as terminal electron acceptor. NADPH oxidation responded to changes
in Ca2+ concentrations more rapidly than NADH oxidation did. Thus, cytosolic
acidification is an important activator of external NADPH oxidation, by
decreasing the Ca2+-requirements for NDB1. The results are discussed in relation
to the present knowledge on how whole cell NADPH redox homeostasis is affected in
plants modified for the NDB1 gene.
PMID- 26413896
TI - Potential risk and control strategy of biofilm pretreatment process treating raw
water.
AB - An enhanced lab-scale biofilm pretreatment process treating raw water obtained
from eutrophicated water bodies was established and started up with a novel
strategy of low-level nutrients addition and effluent recirculation. Results
showed that the startup strategy was useful for biofilm formation and pollutants
removal, but it had the risks of increasing substrate affinity constant (Ks) and
biofilm decay in treating raw water. Fortunately, the increased Ks value did not
affected the NH4(+)-N removal performance via keeping the NH4(+)-N loading rate
larger than 6.29 mg L(-1)d(-1). In addition, lower hydraulic retention time (HRT)
favored the removal of organic matters, and the maximum TOC removal rate of 76.5
mg L(-1)d(-1) were achieved at HRT of 2h. After long-term acclimatization at
oligotrophic niche, the decrease of Ks value and increase of biomass,
extracellular polymeric substances, bioactivity were achieved. Finally, the
stable operation of biofilm pretreatment process was realized in treating
polluted raw water.
PMID- 26413897
TI - A Ca-alginate particle co-immobilized with Phanerochaete chrysosporium cells and
the combined cross-linked enzyme aggregates from Trametes versicolor.
AB - For improving stability of immobilized white-rot fungus to treat various
effluents, Phanerochaete chrysosporium cells and the combined cross-link enzyme
aggregates (combi-CLEAs) prepared from Trametes versicolor were co-immobilized
into the Ca-alginate gel particles in this paper. The activity yields of obtained
combi-CLEAs were 42.7% for lignin peroxidases (LiPs), 31.4% for manganese
peroxidases (MnPs) and 40.4% for laccase (Lac), respectively. And their specific
activities were 30.2U/g as combi-CLEAs-LiPs, 9.5 U/g as combi-CLEAs-MnPs and 28.4
U/g as combi-CLEAs-Lac. Further, the present of the combi-CLEAs in the particles
extremely improved their ability to degrade the dyes. Compared to the immobilized
Ph. chrysosporium without the combi-CLEAs, the co-immobilized particles enhanced
the decolorized rate of Acid Violet 7 (from 45.2% to 93.4%) and Basic Fuchsin
(from 12.1% to 67.9%). In addition, the addition of the combi-CLEAs improved the
adaptability of the white-rot fungal particles to adverse environmental
conditions.
PMID- 26413898
TI - Effectiveness of Training Clinicians' Communication Skills on Patients' Clinical
Outcomes: A Systematic Review.
AB - OBJECTIVE: The aim of this systematic review was to investigate the literature on
the effectiveness of communication skills training for clinicians on patients'
clinical outcomes in primary care and rehabilitation settings. METHODS: We
systematically reviewed the literature for randomized controlled trials
investigating the effectiveness of communication skills training for clinicians
on patients' satisfaction with care and on pain and disability in primary care
and rehabilitation settings. The search strategy was conducted using AMED,
PsycINFO, MEDLINE, CINAHL, EMBASE, PEDro, and Cochrane Central Register of
Controlled Trials through June 2015. Methodological quality of included trials
was assessed by 2 independent investigators using the PEDro scale, and consensus
was used to resolve disagreements. Data were extracted, and meta-analyses were
performed. RESULTS: Nineteen randomized controlled trials were included. Of
these, 16 investigated communication training for clinicians that emphasized
patient participation (eg, shared decision-making approaches). Communication
training had small effects on patients' satisfaction with care when compared to
control (4.1 points on a 100-point scale, 95% confidence interval [CI], 1.1-7.0).
Communication training also had small effects on pain and disability with pooled
results showing weighted mean differences of -3.8 points (95% CI, -6.5 to -1.1)
and -3.6 (95% CI, -5.4 to -1.7), respectively. CONCLUSIONS: Studies show that
communication training for clinicians produces small effects in improving
patients' satisfaction with care or reducing pain and disability in primary care
and rehabilitation settings.
PMID- 26413899
TI - Neuromechanical responses after biofeedback training in participants with chronic
low back pain: an experimental cohort study.
AB - OBJECTIVE: The objective of this study was to evaluate changes in neuromechanical
responses and clinical outcomes in chronic low back pain participants after 4
sessions of biofeedback training. METHODS: Twenty-one participants took part in
an electromyography biofeedback 4-session training program aimed at reducing
lumbar paraspinal muscle activity during full trunk flexion. The sessions
consisted of ~46 trunk flexion-extension divided into 5 blocks. The effects of
training blocks and sessions on lumbar flexion-relaxation ratio and lumbopelvic
ranges of motion were assessed. Changes in disability (Oswestry Disability
Index), pain intensity (numerical rating scale), and fear of movement (Tampa
Scale for Kinesiophobia) were also evaluated. RESULTS: Analyses of variance
revealed a significant block effect for which an increase in the flexion
relaxation ratio and the lumbar range of motion between block 1 and the other
blocks for sessions 1 and 2 (P < .0001) was observed. However, no significant
session or interaction effect was observed. Among clinical outcomes, only fear of
movement significantly decreased between the baseline (mean [SD], 33.05 [7.18])
and the fourth session (29.80 [9.88]) (P = .02). There was no significant
correlation between clinical outcomes and neuromechanical variables. CONCLUSION:
Biofeedback training led to decreases in lumbar paraspinal muscle activity in
full trunk flexion and increases in lumbopelvic range of motion in participants
with chronic nonspecific low back pain. Although the neuromechanical changes were
mostly observed at the early stage of the program, the presence of a decrease in
the fear of movement suggests that the participants' initially limited ROMs may
have been modulated by fear avoidance behaviors.
PMID- 26413900
TI - Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or
Aerosol Exposure.
AB - Marburg virus infection in humans causes a hemorrhagic disease with a high case
fatality rate. Countermeasure development requires the use of well-characterized
animal models that mimic human disease. To further characterize the cynomolgus
macaque model of MARV/Angola, two independent dose response studies were
performed using the intramuscular or aerosol routes of exposure. All animals
succumbed at the lowest target dose; therefore, a dose effect could not be
determined. For intramuscular-exposed animals, 100 PFU was the first target dose
that was not significantly different than higher target doses in terms of time to
disposition, clinical pathology, and histopathology. Although a significant
difference was not observed between aerosol-exposed animals in the 10 PFU and 100
PFU target dose groups, 100 PFU was determined to be the lowest target dose that
could be consistently obtained and accurately titrated in aerosol studies.
PMID- 26413901
TI - Megacystis microcolon intestinal hypoperistalsis syndrome: A report of a
nationwide survey in Japan.
AB - BACKGROUND: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is
a rare condition with a poor outcome. A nationwide survey was conducted to
identify the clinical features and outcomes of MMIHS in Japan. METHODS: Data were
collected via a questionnaire, which was sent to 353 pediatric/pediatric surgical
departments in Japan. RESULTS: Of the 28 patients registered as having a certain
diagnosis of MMIHS, 19 (male/female, 3/16) patients were analyzed. All of the
patients developed functional bowel obstruction in the neonatal period and showed
a distended bladder and microcolon in the radiological examination. A
histopathology assessment of the full-thickness of intestinal specimens showed no
pathological abnormalities in all patients. Although various medications were
given, the patients did not show significant improvement. Drainage stomas were
created in the jejunum (n=11) and colon (n=5). Sixteen patients were maintained
by parenteral nutrition (PN). Nine patients died of sepsis or liver failure. The
five- and ten-year survival rates were 63% and 57%, respectively. CONCLUSIONS:
MMIHS patients developed severe functional intestinal obstruction in the neonatal
period and had no specific therapeutic intervention. The majority of MMIHS
patients required long-term PN. Small bowel or multivisceral transplantation may
be necessary to improve the outcome of this condition.
PMID- 26413902
TI - Cardiac fetal ultrasonographic parameters for predicting outcomes of isolated
left-sided congenital diaphragmatic hernia.
AB - BACKGROUND: The purpose of this study was to investigate fetal cardiac
ultrasonographic parameters in relation to the outcomes of patients with isolated
left-sided congenital diaphragmatic hernia (CDH). METHODS: Subjects comprised 33
fetuses with fetal CDH and 99 control fetuses without cardiac and lung anomalies.
Three parameters, cardiothoracic area ratio (CTAR), the ratio of the diameter of
the main pulmonary artery to that of the ascending aorta (MPA/AAo), and the ratio
of the diameter of the tricuspid valve to that of the mitral valve (TV/MV) were
compared between fetal CDH and control subjects and between survival (SG) and non
survival (NSG) groups. RESULTS: All three parameters differed significantly
between CDH and control fetuses. Significant differences between SG and NSG were
observed in CTAR and TV/MV ratio, but not in MPA/AAo ratio before and after 32
gestational weeks. A significant increase in the TV/MV ratio was noted along with
an increase in gestational age. A TV/MV ratio of >1.72 discriminated non
survivors from survivors with better sensitivity and specificity. CONCLUSIONS:
Fetal cardiac ultrasonography provides useful information for predicting the
outcomes of isolated left-sided CDH. The TV/MV ratio was considered a reliable
indicator that reflected outcomes of isolated left-sided CDH.
PMID- 26413903
TI - The Association of Gender, Age, Efavirenz Use, and Hypovitaminosis D Among HIV
Infected Adults Living in the Tropics.
AB - Vitamin D, which is important for calcium homeostasis and bone metabolism, has
several noncalcemic actions. Low vitamin D levels have been observed in HIV
infected patients from high latitudes, with consequently reduced bone mineral
density (BMD), but data from the tropics are scarce. We aimed to determine the
prevalence of and risk factors for hypovitaminosis D among HIV-infected patients
in the tropics. This was a cross-sectional study to determine serum 25
hydroxyvitamin D [25(OH)D] levels in HIV-infected patients who attended our HIV
clinic in Bangkok, Thailand from July 2010 to June 2011. Hypovitaminosis D was
defined as vitamin D insufficiency and deficiency [25(OH)D 20-30 ng/ml and <20
ng/ml, respectively]. Hypovitaminosis D prevalence was calculated and risk
factors were determined using multivariate logistic regression. A total of 673
HIV-infected adults were included. The median age was 41 years and 47% were
females. The median body mass index (BMI) was 21.9 kg/m(2) and 93% were using
antiretroviral therapy (ART), with a median (IQR) duration of 8.9 (5.0-10.4)
years. Thirty-one percent were using efavirenz (EFV). The prevalence of vitamin D
insufficiency and deficiency was 40.6% and 29.9%, respectively. In multivariate
analysis, female gender [odds ratio: OR (95% confidence interval: 95% CI) 1.7
(1.2-2.3), p = 0.005], age >37 years [OR (95% CI) 1.6 (1.1-2.4), p = 0.01], and
EFV use [OR (95% CI) 2.0 (1.3-3.2), p = 0.004] were independent predictors of
hypovitaminosis D. Even in tropical areas where the sun is abundant,
hypovitaminosis D is highly prevalent. Thus, treatment of low vitamin D in HIV
infected patients at high risk should not be ignored to prevent reductions in BMD
and other hypovitaminosis D-related comorbidities.
PMID- 26413904
TI - Effect of starting body fat content and genotype of laying hens on the changes in
their live weight, body fat content, egg production and egg composition during
the first egg-laying period.
AB - A total 120 laying hens (60 TETRA BLANCA white egg layers and 60 TETRA SL brown
egg layers) were selected from 250 TETRA BLANCA and 250 TETRA SL pullets based on
their predicted body fat content by means of computed tomography (CT) at 16 weeks
of age. Three groups of pullets were chosen for the investigation with the
highest (n = 20), lowest (n = 20) and average (n = 20) body fat content. Changes
in the live weight, body fat content, egg production and egg composition of the
chosen animals were recorded at 32, 52 and 72 weeks of age. Based on the results,
it was established that differences in starting body fat content of the hens
remained the same during the experimental period. The differences between the two
extreme groups were statistically significant at each age. The starting body fat
content of the hens affected the rate of egg production, i.e. hens with high
starting body fat content produced 11-14 eggs fewer than the hens with a low or
average body fat content but had no effect on the composition of the eggs.
Genotype affected almost all of the examined traits: TETRA BLANCA hens had lower
live weight and higher body fat content during the experimental period and
produced fewer eggs with lower albumen and higher yolk, dry matter and crude fat
content than the TETRA SL hens.
PMID- 26413905
TI - Serendipitous Meta-Transcriptomics: The Fungal Community of Norway Spruce (Picea
abies).
AB - After performing de novo transcript assembly of >1 billion RNA-Sequencing reads
obtained from 22 samples of different Norway spruce (Picea abies) tissues that
were not surface sterilized, we found that assembled sequences captured a mix of
plant, lichen, and fungal transcripts. The latter were likely expressed by
endophytic and epiphytic symbionts, indicating that these organisms were present,
alive, and metabolically active. Here, we show that these serendipitously
sequenced transcripts need not be considered merely as contamination, as is
common, but that they provide insight into the plant's phyllosphere. Notably, we
could classify these transcripts as originating predominantly from
Dothideomycetes and Leotiomycetes species, with functional annotation of gene
families indicating active growth and metabolism, with particular regards to
glucose intake and processing, as well as gene regulation.
PMID- 26413906
TI - UV-Visible and Plasmonic Nanospectroscopy of the CO2 Adsorption Energetics in a
Microporous Polymer.
AB - In the context of carbon capture and storage (CCS), micro- and mesoporous
polymers have received significant attention due to their ability to selectively
adsorb and separate CO2 from gas streams. The performance of such materials is
critically dependent on the isosteric heat of adsorption (Qst) of CO2 directly
related to the interaction strength between CO2 and the adsorbent. Here, we show
using the microporous polymer PIM-1 as a model system that its Qst can be
conveniently determined by in situ UV-vis optical transmission spectroscopy
directly applied on the adsorbent or, with higher resolution, by indirect
nanoplasmonic sensing based on localized surface plasmon resonance in metal
nanoparticles. Taken all together, this study provides a general blueprint for
efficient optical screening of micro- and mesoporous polymeric materials for CCS
in terms of their CO2 adsorption energetics and kinetics.
PMID- 26413907
TI - Novelties in the management of B-cell malignancies: B-cell receptor signaling
inhibitors and lenalidomide.
AB - B-cell lymphoproliferative disorders comprise 85% of Non-Hodgkin's lymphomas.
Despite successful chemoimmunotherapy regimens, responses are not durable and the
outcome is fatal in a considerable portion of patients. There is an inevitable
need for less toxic and more potent therapeutic agents. Over the recent years, a
plethora of agents including monoclonal antibodies, Bcl-2 antagonists, tyrosine
kinase inhibitors, cyclin-dependent kinase inhibitors, mTOR inhibitors and
immunomodulatory drugs have been developed in B-cell malignancies. The aim of
this paper is to focus on B-cell receptor signaling inhibitors and lenalidomide
as an immunomodulatory drug and to provide insight on how and when to incorporate
these agents into the treatment algorithms.
PMID- 26413909
TI - Crossed Molecular Beams and Quasiclassical Trajectory Surface Hopping Studies of
the Multichannel Nonadiabatic O((3)P) + Ethylene Reaction at High Collision
Energy.
AB - The combustion relevant O((3)P) + C2H4 reaction stands out as a prototypical
multichannel nonadiabatic reaction involving both triplet and singlet potential
energy surfaces (PESs), which are strongly coupled. Crossed molecular beam (CMB)
scattering experiments with universal soft electron ionization mass spectrometric
detection have been used to characterize the dynamics of this reaction at the
relatively high collision energy Ec of 13.7 kcal/mol, attained by crossing the
reactant beams at an angle of 135 degrees . This work is a full report of the
data at the highest Ec investigated for this reaction. From laboratory product
angular and velocity distribution measurements, angular and translational energy
distributions in the center-of-mass system have been obtained for the five
observed exothermic competing reaction channels leading to H + CH2CHO, H + CH3CO,
CH3 + HCO, CH2 + H2CO, and H2 + CH2CO. The product branching ratios (BRs) have
been derived. The elucidation of the reaction dynamics is assisted by synergic
full-dimensional quasiclassical trajectory surface-hopping calculations of the
reactive differential cross sections on coupled ab initio triplet/singlet PESs.
This joint experimental/theoretical study extends and complements our previous
combined CMB and theoretical work at the lower collision energy of 8.4 kcal/mol.
The theoretically derived BRs and extent of intersystem crossing (ISC) are
compared with experimental results. In particular, the predictions of the QCT
results for the three main channels (those leading to vinoxy + H, methyl + HCO
and methylene + H2CO formation) are compared directly with the experimental data
in the laboratory frame. Good overall agreement is noted between theory and
experiment, although some small, yet significant shortcomings of the theoretical
differential cross section are noted. Both experiment and theory find almost an
equal contribution from the triplet and singlet surfaces to the reaction, with a
clear tendency of the degree of ISC to decrease with increasing Ec and with
theory slightly overestimating the extent of ISC.
PMID- 26413908
TI - A Fluorinated Ligand Enables Room-Temperature and Regioselective Pd-Catalyzed
Fluorination of Aryl Triflates and Bromides.
AB - A new biaryl monophosphine ligand (AlPhos, L1) allows for the room-temperature Pd
catalyzed fluorination of a variety of activated (hetero)aryl triflates.
Furthermore, aryl triflates and bromides that are prone to give mixtures of
regioisomeric aryl fluorides with Pd-catalysis can now be converted to the
desired aryl fluorides with high regioselectivity. Analysis of the solid-state
structures of several Pd(II) complexes, as well as density functional theory
(DFT) calculations, shed light on the origin of the enhanced reactivity observed
with L1.
PMID- 26413910
TI - Neuroimaging Biomarkers of a History of Concussion Observed in Asymptomatic Young
Athletes.
AB - Participation in contact sports places athletes at elevated risk for repeated
head injuries and is associated with negative mental health outcomes later in
life. The current study identified changes observable on neuroimaging that
persisted beyond the apparent resolution of acute symptoms of concussion. Sixteen
young adult ice hockey players with a remote history of concussion but no
subjective complaints were compared against 13 of their teammates with no history
of concussion. Participants completed a detailed phenotypic assessment and a
neuroimaging battery including diffusion kurtosis imaging and resting-state
functional magnetic resonance imaging. Athletes with a history of concussion
performed no differently from those without on phenotypic assessment, but showed
significantly elevated fractional anisotropy (FA) in the left genu and anterior
corona radiata relative to those without. Post hoc analyses revealed that
elevated FA was associated with increased microstructural complexity
perpendicular to the primary axon (radial kurtosis). Athletes with concussion
history also showed significant differences in the organization of the default
mode network (DMN) characterized by stronger temporal coherence in posterior DMN,
decreased temporal coherence in anterior DMN, and increased functional
connectivity outside the DMN. In the absence of deficits on detailed phenotypic
assessment, athletes with a history of concussion displayed changes to the
microstructural architecture of the cerebral white matter and to the functional
connectivity of the brain at rest. Some of these changes are consistent with
those previously associated with persisting deficits and complaints, but we also
report novel, complementary changes that possibly represent compensatory
mechanisms.
PMID- 26413911
TI - Folate Receptor Alpha Immunohistochemistry in Cytology Specimens of Metastatic
Breast Carcinoma.
AB - BACKGROUND: Folate receptor alpha (FRA) is involved in folate accumulation and
utilization, and is expressed in varying proportions in breast, ovary and parotid
epithelial cells, among others. FRA overexpression by immunohistochemistry (IHC)
has been shown in estrogen/progesterone receptor (ER/PR)-negative carcinoma (40
74%) and in triple-negative breast carcinoma (TNBC; 50-86%) in histological
specimens of primary breast cancers. We assessed the feasibility of IHC in
detecting FRA expression and its patterns and clinical significance in metastatic
TNBC in fine-needle aspiration (FNA) cell blocks (CBs). MATERIALS AND METHODS:
Metastatic breast ductal carcinoma cases were retrospectively immunostained with
FRA IHC on FNA CBs. FRA staining was scored qualitatively (+/-), by intensity (0
3) and by staining area (0-100%). Of these metastatic cases, a subset of primary
breast carcinoma cases was also immunostained with FRA. The results were
correlated with ER, PR and human epidermal growth factor receptor 2 (Her2/Neu)
performed by routine IHC. RESULTS: A total of 40 FNA CBs with metastatic disease
were studied, including hormone (ER/PR) positive (n = 5), triple positive (n =
5), Her2/Neu-only positive (n = 5) and TNBC (n = 25). FRA IHC showed
immunoreactivity with moderate positivity in only 1 (4%) TNBC. All the remaining
39 cases were negative for FRA expression. Five cases of primary TNBC were
stained with FRA IHC and were negative for FRA expression. CONCLUSIONS: Our data
suggest that FRA expression by IHC was rarely associated with ER/PR-negative
tumors relative to ER/PR-positive tumors and, more importantly, with TNBC in FNA
CBs. This finding may have a clinical significance and prognostic implications in
metastatic breast carcinoma. Furthermore, 5 primary TNBC cases did not
overexpress FRA by IHC. Hence, antifolate receptor therapies do not appear to be
clinically relevant in TNBC based on immunostaining of FNA CBs of metastatic
breast cancers.
PMID- 26413912
TI - Fatty acid amide hydrolase inhibitors: a patent review (2009-2014).
AB - INTRODUCTION: Fatty acid amide hydrolase (FAAH) is a key enzyme responsible for
the degradation of the endocannabinoid anandamide. FAAH inactivation is emerging
as a strategy to treat several CNS and peripheral diseases, including
inflammation and pain. The search for effective FAAH inhibitors has thus become a
key focus in present drug discovery. AREAS COVERED: Patents and patent
applications published from 2009 to 2014 in which novel chemical classes are
claimed to inhibit FAAH. EXPERT OPINION: FAAH is a promising target for treating
many disease conditions including pain, inflammation and mood disorders. In the
last few years, remarkable efforts have been made to develop new FAAH inhibitors
(either reversible and irreversible) characterized by excellent potency and
selectivity, to complete the arsenal of tools for modulating FAAH activity. The
failure of PF-04457845 in a Phase II study on osteoarthritis pain has not
flattened the interest in FAAH inhibitors. New clinical trials on 'classical'
FAAH inhibitors are now ongoing, and new strategies based on compounds with
peculiar in vivo distribution (e.g., peripheral) or with multiple pharmacological
activities (e.g., FAAH and COX) are under investigation and could boost the
therapeutic potential of this class in the next future.
PMID- 26413920
TI - Rare case of external dental fistula of the submental region misdiagnosed as
inverted follicular keratosis and thyroglossal duct cyst.
AB - INTRODUCTION: Odontogenic cutaneous sinus tract is a relatively rare occurrence
that can be complicated to diagnose. The presence of a cutaneous lesion is often
not even partly associated with a dental etiology because of the less frequency
of occurrence in the case of dental symptoms. Consequently, the underlying dental
cause is often missed leading to inappropriate diagnosis and treatment. CASE
PRESENTATION: Here, we report the case of a 45-year-old man who presented with a
persistent lesion of the cervical region. At the time of presentation, the lesion
had been present for approximately one year with a gradual increase in size but
no specific symptoms. The patient had previously undergone punch resection under
local anesthesia, which resulted in a histopathological diagnosis of inverted
follicular keratosis. A diagnosis was made of an odontogenic cutaneous sinus
tract secondary to chronic apical periodontitis of the left mandibular second
molar. DISCUSSION: Cutaneous sinus tract in the face and neck is most likely to
develop intraorally. Root canal treatment or surgical extractions are the common
treatment choices. A previously reported review of 137 cases found that 106 (77%)
were treated by extraction and 27 (20%) were treated by surgical or conservative
nonsurgical endodontic therapy. CONCLUSION: Early diagnosis of cutaneous sinus
tract using proper aid is responsible for shortening the treatment duration and
avoiding unnecessary treatment.
PMID- 26413921
TI - Huge hepatocellular carcinoma with multiple intrahepatic metastases: An
aggressive multimodal treatment.
AB - INTRODUCTION: Huge hepatocellular carcinoma (HCC) possesses a potential risk for
spontaneous rupture, which leads to a life-threatening complication with a high
mortality rate. In addition, a large HCC is frequently accompanied by
intrahepatic metastases. PRESENTATION OF CASE: We describe, the case of a 74-year
old woman with a huge extrahepatically expanding HCC with multiple intrahepatic
metastases who was treated by liver resection with repeated transcatheter
arterial chemoembolization (TACE). To prevent tumor rupture or bleeding, we
performed right hepatectomy. After the operation, TACE was applied for multiple
intrahepatic metastases in the remnant liver. Furthermore, the elevated protein
induced vitamin K absence (PIVKA II) level had decreased to limits within the
normal range. Three months after the first TACE, computed tomography revealed
several recurrences in the liver. TACE was applied for the second and third time
and the tumors were well controlled. DISCUSSION: Although, liver resection is
occasionally performed for patients with huge HCC to avoid spontaneous tumor
rupture, only surgical approach might not be sufficient for such advanced HCC. To
achieve long-term survival, it is necessary to control the residual intrahepatic
tumors. We could control multiple intrahepatic metastases with repeated TACEs
after hepatectomy. CONCLUSION: Multimodal treatment involving hepatectomy and
TACE might be a good treatment strategy for patients with huge HCC with multiple
intrahepatic metastases if the tumors are localized in the liver without distant
or peritoneal metastasis.
PMID- 26413922
TI - Unusual presentation of a Meckel's diverticulum: A case report.
AB - INTRODUCTION: Meckel's diverticulum (MD) is the most common congenital
malformation of the gastrointestinal tract. Intestinal obstruction is the lead
presenting symptom in the adult population due to multiple causes
(intussusception, incarceration, adhesions, strictures and torsion). Our patient
had a complicated MD with an unique combination of risk factors and findings.
PRESENTATION OF CASE: We report an unusual case of an 18-year-old patient
presenting with acute small bowel obstruction for several days, who developed
focal peritoneal signs on right lower quadrant. On laparotomy, findings included
a necrotic giant MD and a small bowel volvulus around a fibrous band that
attached MD to the umbilicus. Segmental enterectomy with primary anastomosis was
performed. DISCUSSION: Axial torsion and gangrene of MD is the rarest
complication. Its pre-operative diagnosis remains elusive as it can be clinically
indistinguishable from other intra-abdominal inflammatory conditions. The correct
diagnosis of complicated MD before surgery is often difficult because this
condition can mimic other acute abdominal pathologies. There are several risk
factors that can point to an accurate and early diagnosis, especially when
combined with the appropriate imaging techniques, such as computed tomography
with oral and intravenous contrast. CONCLUSION: This complication remains
underdiagnosed, often with delayed surgical intervention and sub-optimal
treatment that leads to significant morbidity and mortality.
PMID- 26413923
TI - The hanging manoeuver to complete liver resection for a locally advanced
angiosarcoma: A case report.
AB - INTRODUCTION: Angiosarcomas arising in the liver are rare tumours in the Western
world. We report a case of a locally advanced primary hepatic angiosarcoma and
also describe the manoeuvres used to achieve operative resection. PRESENTATION OF
A CASE: A 52-year old woman presented with vague right upper quadrant pain.
Abdominal imaging revealed a heterogenous tumour in the right liver measuring
15centimetres in maximal diameter. Although the tumour was deemed to be
resectable, there was free fluid in the right paracolic gutter suggestive of
rupture. Intra-operatively, the peritoneal cavity was noted to be free of
metastatic disease. However, tumour was adherent to the diaphragm precluding
traditional mobilization of the liver. Therefore, a modified hanging manoeuvre
was performed using a nasogastric tube. This allowed controlled mobilization of
the right liver, parenchymal transection and en-bloc resection of the diaphragm
with good hemostasis. Histologic examination revealed a primary angiosarcoma with
uninvolved margins. DISCUSSION: When they occur, primary hepatic angiosarcomas
are most often locally advanced. Nevertheless, surgeons should be aggressive in
the pursuit of complete resections because this is the only therapeutic modality
that has been shown to have a survival advantage. CONCLUSION: Hepatobiliary
surgeons should keep the hanging manoeuver in their armamentarium when performing
complex liver resections for locally advanced angiosarcomas.
PMID- 26413924
TI - Total laparoscopic subtotal gastrectomy with transvaginal specimen extraction is
feasible in advanced gastric cancer.
AB - PURPOSE: Natural orifice specimen extraction (NOSE) is an ever-evolving advanced
laparoscopic technique. NOSE minimizes surgical injury, involving a low risk of
wound complications, fewer incisional hernias, faster recovery and less
postoperative pain. Laparoscopic gastrectomy combined with NOSE is a procedure
that can potentiate the advantages of both minimal invasive techniques. We aim to
demonstrate the feasibility of laparoscopic subtotal gastrectomy with
transvaginal specimen extraction in advanced gastric cancer. CASE: A 72-year-old
woman with a 2cm adenocarcinoma in gastric antrum was treated by laparoscopic
subtotal gastrectomy and lymph node dissection. A totally laparoscopic Roux-en-Y
gastrojejunostomy was constructed. Specimen was extracted through the posterior
fornix of vagina without difficulty. Histopathology confirmed pT3pN0 tumor. After
a 10-month follow-up the patient was asymptomatic and getting adjuvant
chemoradiotherapy. CONCLUSIONS: Transvaginal specimen extraction after
laparoscopic gastric resection for advanced gastric cancer is a feasible
procedure. It is offered to selected patients and of course only to female
patients. Natural orifice surgery may provide faster recovery and decrease the
wound related complications which may cause a delay on postoperative adjuvant
chemo-radio therapies. We have presented, as far as we know, the first human case
of a transvaginal extraction of an advanced gastric cancer after laparoscopic
gastrectomy.
PMID- 26413925
TI - Relationship Between Disease Characteristics and Oral Radiologic Findings in
Systemic Sclerosis: Results From a Canadian Oral Health Study.
AB - OBJECTIVE: Systemic sclerosis (SSc; scleroderma) is associated with a wide
periodontal ligament (PDL) and mandibular erosions. We investigated the clinical
correlates of SSc with these radiologic abnormalities. METHODS: Subjects from the
Canadian Scleroderma Research Group cohort underwent detailed radiologic
examinations. Associations between radiologic abnormalities and clinical
manifestations of SSc were examined with univariate and multivariate analyses.
RESULTS: The study included 159 subjects; 90.6% were women, the mean +/- SD age
was 56 +/- 10 years, diffuse disease was present in 28.3%, and mean +/- SD
disease duration was 13.7 +/- 8.4 years. Widening of the PDL involving at least 1
tooth was present in 38% of subjects, and 14.5% had at least 1 site in the
mandible with an erosion. In analyses adjusting for age, disease duration, sex,
smoking, and education, we found significant associations between the number of
teeth with widening of the PDL and disease severity assessed by the physician
global assessment (PGA) (relative risk [RR] 1.19, 95% confidence interval [95%
CI] 1.02-1.39, P = 0.028). Analyses replacing the PGA with the skin score,
disease subset, or anti-topoisomerase I antibodies confirmed the relationship
with indices of disease severity. There was no relationship between either the
number of teeth with periodontal disease or the number of missing teeth, and the
number of teeth with wide PDL. A smaller interdental distance (RR 0.89, 95% CI
0.82-0.97, P = 0.006), but not disease severity, facial skin score, or ischemia
was associated with a larger number of erosions. CONCLUSION: In SSc, a wide PDL
may reflect generalized overproduction of collagen, and mandibular erosions are
related to local factors in the oral cavity.
PMID- 26413926
TI - Topography-Guided Proliferation: Distinct Surface Microtopography Increases
Proliferation of Chondrocytes In Vitro.
AB - Chondrocyte-based cartilage repair techniques require control of articular
chondrocyte expansion ex vivo. Articular chondrocytes have limited availability,
and prolonged culturing to obtain a cell number sufficient for clinical use often
results in phenotypic alterations and increased costs. In this study, we applied
a screening library consisting of micrometer-sized topographical features, termed
biosurface structure array (BSSA), to identify specific topographical
microstructures affecting the proliferation of human chondrocytes in passage 1
(P1) or 2 (P2). The BSSA library comprised 10 patterns and 16 combinations of
pillar size (X) and interpillar gap size (Y). Specific microstructures
significantly increased the chondrocytes' proliferative responsiveness in term of
patterns, X and Y for P2 compared with P1. The P1 and P2 chondrocytes responded
independently to similar patterns after 4 days of culturing, whereas only
chondrocytes at P2 responded to specific microstructures with Y = 1 MUm and X =
2, 4 MUm by a 2.3- and 4.4-fold increased proliferation, respectively. In
conclusion, these findings indicate that specific surface topographies promote
chondrocyte proliferation and may, indeed, be a tool to control the behavior of
chondrocytes in vitro.
PMID- 26413927
TI - A Pilot Study of In Vivo Confocal Laser Endomicroscopy of Upper Tract Urothelial
Carcinoma.
AB - PURPOSE: Tissue diagnosis of upper tract urothelial carcinoma (UTUC) is limited
by variance in tumor sampling by standard ureteroscopic biopsy. Optical imaging
technologies can potentially improve UTUC diagnosis, surveillance, and endoscopic
treatment. We previously demonstrated in vivo optical biopsy of urothelial
carcinoma of the bladder using confocal laser endomicroscopy (CLE). In this
study, we evaluated a new 0.85-mm imaging probe in the upper urinary tract and
demonstrated feasibility and compatibility with standard ureteroscopes to achieve
in vivo optical biopsy of UTUC. MATERIALS AND METHODS: Fourteen patients
scheduled for ureteroscopy of suspected upper tract lesions or surveillance of
UTUC were recruited. After intravenous (IV) administration of fluorescein, CLE
was performed using a 0.85-mm-diameter imaging probe inserted through the working
channel of standard ureteroscopes. Acquired confocal video sequences were
reviewed and analyzed. A mosaicing algorithm was used to compile a series of
images into a single larger composite image. Processed CLE images were compared
with standard histopathologic analysis. RESULTS: Optical biopsy of the UTUC using
CLE was effectively achieved during standard ureteroscopy. There were no adverse
events related to IV fluorescein administration or image acquisition. Confocal
imaging of UTUC showed characteristic features similar to urothelial carcinoma of
the bladder, including papillary structure, fibrovascular stalks, and
pleomorphism. Lamina propria in normal areas of the renal pelvis and ureter was
also identified. CONCLUSIONS: We report an initial feasibility of CLE of UTUC.
Pending further clinical investigation, CLE may become a useful adjunct to
ureteroscopic biopsy, endoscopic ablation, and surveillance of UTUC.
PMID- 26413928
TI - Silent Atrial Fibrillation in Elderly Pacemaker Users: A Randomized Trial Using
Home Monitoring.
AB - BACKGROUND: Pacemaker with remote monitoring (PRM) may be useful for silent
atrial fibrillation (AF) detection. The aims of this study were to evaluate the
incidence of silent AF, the role of PRM, and to determine predictors of silent AF
occurrence. METHODS: Three hundred elderly patients with permanent pacemaker
(PPM) were randomly assigned to the remote group (RG) or control group (CG). All
patients received PPM with remote monitoring capabilities. Primary end point was
AF occurrence rate and the secondary end points were time to AF detection and
number of days with AF. RESULTS: During the average follow-up of 15.7+/-7.7
months, AF episodes were detected in 21.6% (RG = 24% vs CG = 19.3%, P = 0.36].
There was no difference in the time to detect the first AF episode. However, the
median time to detect AF recurrence in the RG was lower than that in the CG (54
days vs 100 days, P = 0.004). The average number of days with AF was 16.0 and
51.2 in the RG and CG, respectively (P = 0.028). Predictors of silent AF were
left atrial diameter (odds ratio [OR] 1.2; 95% CI = 1.1-1.3; P < 0.001) and
diastolic dysfunction (OR 4.8; 95% CI = 1.6-14.0; P = 0.005). CONCLUSIONS: The
incidence of silent AF is high in elderly patients with pacemaker; left atrial
diameter and diastolic dysfunction were predictors of its occurrence. AF
monitoring by means of pacemaker is a valuable tool for silent AF detection and
continuous remote monitoring allows early AF recurrence detection and reduces the
number of days with AF.
PMID- 26413929
TI - Phototherapy-Induced Antitumor Immunity: Long-Term Tumor Suppression Effects via
Photoinactivation of Respiratory Chain Oxidase-Triggered Superoxide Anion Burst.
AB - AIMS: Our previous studies have demonstrated that as a mitochondria-targeting
cancer phototherapy, high-fluence, low-power laser irradiation (HF-LPLI) results
in oxidative damage that induces tumor cell apoptosis. In this study, we focused
on the immunological effects of HF-LPLI phototherapy and explored its antitumor
immune regulatory mechanism. RESULTS: We found not only that HF-LPLI treatment
induced tumor cell apoptosis but also that HF-LPLI-treated apoptotic tumor cells
activated macrophages. Due to mitochondrial superoxide anion burst after HF-LPLI
treatment, tumor cells displayed a high level of phosphatidylserine oxidation,
which mediated the recognition and uptake by macrophages with the subsequent
secretion of cytokines and generation of cytotoxic T lymphocytes. In addition, in
vivo results showed that HF-LPLI treatment caused leukocyte infiltration into the
tumor and efficaciously inhibited tumor growth in an EMT6 tumor model. These
phenomena were absent in the respiration-deficient EMT6 tumor model, implying
that the HF-LPLI-elicited immunological effects were dependent on the
mitochondrial superoxide anion burst. INNOVATION: In this study, for the first
time, we show that HF-LPLI mediates tumor-killing effects via targeting
photoinactivation of respiratory chain oxidase to trigger a superoxide anion
burst, leading to a high level of oxidatively modified moieties, which
contributes to the phenotypic changes in macrophages and mediates the antitumor
immune response. CONCLUSION: Our results suggest that HF-LPLI may be an effective
cancer treatment modality that both eradicates the treated primary tumors and
induces an antitumor immune response via photoinactivation of respiratory chain
oxidase to trigger superoxide anion burst.
PMID- 26413930
TI - A Solid Phase Vibrational Circular Dichroism Study of Polypeptide-Surfactant
Interaction.
AB - We studied the interaction of poly-l-lysine (PLL) and poly-l-arginine (PLAG) with
sodium dodecyl sulfate (SDS) surfactant and the interaction of poly-l-glutamic
acid (PLGA) and poly-l-aspartic acid (PLAA) with tetradecyltrimethylammonium
bromide (TTAB) surfactant using vibrational circular dichroism (VCD) spectroscopy
in the region of C-H stretching vibration and in the Amide I region both in
solution and in mulls. A chirality transfer from polypeptides to achiral
surfactants was observed in the C-H stretching region, where measurements in
solution were impossible. This observation was enabled by a special sample
treatment technique using lyophilization and the preparation of mulls. This
technique demonstrated itself as an interesting and beneficial tool for VCD
measurements. In addition, we observed that SDS changed the secondary structure
of PLL to the beta-sheet and of PLAG to the alpha-helix. TTAB disrupted the PLGA
and PLAA structure. These results were obtained in the mull but were confirmed by
the VCD spectra measured in solution and by electronic circular dichroism. The
chirality transfer from the polypeptides to SDS was caused by polypeptides
ordered into a specific conformation during the interaction, while in the TTBA
system it was induced primarily by the chirality of the amino acid residues.
PMID- 26413931
TI - TEMPO-Oxidized Nanofibrillated Cellulose as a High Density Carrier for Bioactive
Molecules.
AB - Controlled and efficient immobilization of specific biomolecules is a key
technology to introduce new, favorable functions to materials suitable for
biomedical applications. Here, we describe an innovative and efficient, two-step
methodology for the stable immobilization of various biomolecules, including
small peptides and enzymes onto TEMPO oxidized nanofibrillated cellulose (TO
NFC). The introduction of carboxylate groups to NFC by TEMPO oxidation provided a
high surface density of negative charges able to drive the adsorption of
biomolecules and take part in covalent cross-linking reactions with 1-ethyl-3-[3
(dimethylamino)propyl]carbodiimide (EDAC) and glutaraldehyde (Ga) chemistry. Up
to 0.27 MUmol of different biomolecules per mg of TO-NFC could be reversibly
immobilized by electrostatic interaction. An additional chemical cross-linking
step prevented desorption of more than 80% of these molecules. Using the cysteine
protease papain as model, a highly active papain-TO-NFC conjugate was achieved.
Once papain was immobilized, 40% of the initial enzymatic activity was retained,
with an increase in kcat from 213 to >700 s(-1) for the covalently immobilized
enzymes. The methodology presented in this work expands the range of application
for TO-NFC in the biomedical field by enabling well-defined hybrid biomaterials
with a high density of functionalization.
PMID- 26413932
TI - SIRT1 Overexpression Maintains Cell Phenotype and Function of Endothelial Cells
Derived from Induced Pluripotent Stem Cells.
AB - Endothelial cells (ECs) that are differentiated from induced pluripotent stem
cells (iPSCs) can be used in establishing disease models for personalized drug
discovery or developing patient-specific vascularized tissues or organoids.
However, a number of technical challenges are often associated with iPSC-ECs in
culture, including instability of the endothelial phenotype and limited cell
proliferative capacity over time. Early senescence is believed to be the primary
mechanism underlying these limitations. Sirtuin1 (SIRT1) is an NAD(+)-dependent
deacetylase involved in the regulation of cell senescence, redox state, and
inflammatory status. We hypothesize that overexpression of the SIRT1 gene in iPSC
ECs will maintain EC phenotype, function, and proliferative capacity by
overcoming early cell senescence. SIRT1 gene was packaged into a lentiviral
vector (LV-SIRT1) and transduced into iPSC-ECs at passage 4. Beginning with
passage 5, iPSC-ECs exhibited a fibroblast-like morphology, whereas iPSC-ECs
overexpressing SIRT1 maintained EC cobblestone morphology. SIRT1 overexpressing
iPSC-ECs also exhibited a higher percentage of canonical markers of endothelia
(LV-SIRT1 61.8% CD31(+) vs. LV-empty 31.7% CD31(+), P < 0.001; LV-SIRT1 46.3%
CD144(+) vs. LV-empty 20.5% CD144(+), P < 0.02), with a higher nitric oxide
synthesis, lower beta-galactosidase production indicating decreased senescence
(3.4% for LV-SIRT1 vs. 38.6% for LV-empty, P < 0.001), enhanced angiogenesis,
increased deacetylation activity, and higher proliferation rate. SIRT1
overexpressing iPSC-ECs continued to proliferate through passage 9 with high
purity of EC-like characteristics, while iPSC-ECs without SIRT1 overexpression
became senescent after passage 5. Taken together, SIRT1 overexpression in iPSC
ECs maintains EC phenotype, improves EC function, and extends cell lifespan,
overcoming critical hurdles associated with the use of iPSC-ECs in translational
research.
PMID- 26413933
TI - Fever Control Management Is Preferable to Mild Therapeutic Hypothermia in
Traumatic Brain Injury Patients with Abbreviated Injury Scale 3-4: A Multi
Center, Randomized Controlled Trial.
AB - In our prospective, multi-center, randomized controlled trial (RCT)-the Brain
Hypothermia (B-HYPO) study-we could not show any difference on neurological
outcomes in patients probably because of the heterogeneity in the severity of
their traumatic condition. We therefore aimed to clarify and compare the
effectiveness of the two therapeutic temperature management regimens in severe
(Abbreviated Injury Scale [AIS] 3-4) or critical trauma patients (AIS 5). In the
present post hoc B-HYPO study, we re-evaluated data based on the severity of
trauma as AIS 3-4 or AIS 5 and compared Glasgow Outcome Scale score and mortality
at 6 months by per-protocol analyses. Consequently, 135 patients were enrolled.
Finally, 129 patients, that is, 47 and 31 patients with AIS 3-4 and 36 and 15
patients with AIS 5 were allocated to the mild therapeutic hypothermia (MTH) and
fever control groups, respectively. No significant intergroup differences were
observed with regard to age, gender, scores on head computed tomography (CT)
scans, and surgical operation for traumatic brain injury (TBI), except for Injury
Severity Score (ISS) in AIS 5. The fever control group demonstrated a significant
reduction of TBI-related mortality compared with the MTH group (9.7% vs. 34.0%, p
= 0.02) and an increase of favorable neurological outcomes (64.5% vs. 51.1%, p =
0.26) in patients with AIS 3-4, although the latter was not statistically
significant. There was no difference in mortality or favorable outcome in
patients with AIS 5. Fever control may be considered instead of MTH in patients
with TBI (AIS 3-4).
PMID- 26413935
TI - Correction: Clinical Utility of a Coronary Heart Disease Risk Prediction Gene
Score in UK Healthy Middle Aged Men and in the Pakistani Population.
PMID- 26413934
TI - A novel role for flotillin-1 in H-Ras-regulated breast cancer aggressiveness.
AB - Elevated expression and aberrant activation of Ras have been implicated in breast
cancer aggressiveness. H-Ras, but not N-Ras, induces breast cell invasion. A
crucial link between lipid rafts and H-Ras function has been suggested. This
study sought to identify the lipid raft protein(s) responsible for H-Ras-induced
tumorigenicity and invasiveness of breast cancer. We conducted a comparative
proteomic analysis of lipid raft proteins from invasive MCF10A human breast
epithelial cells engineered to express active H-Ras and non-invasive cells
expressing active N-Ras. Here, we identified a lipid raft protein flotillin-1 as
an important regulator of H-Ras activation and breast cell invasion. Flotillin-1
was required for epidermal growth factor-induced activation of H-Ras, but not
that of N-Ras, in MDA-MB-231 triple-negative breast cancer (TNBC) cells.
Flotillin-1 knockdown inhibited the invasiveness of MDA-MB-231 and Hs578T TNBC
cells in vitro and in vivo. In xenograft mouse tumor models of these TNBC cell
lines, we showed that flotillin-1 played a critical role in tumor growth. Using
human breast cancer samples, we provided clinical evidence for the metastatic
potential of flotillin-1. Membrane staining of flotillin-1 was positively
correlated with metastatic spread (p = 0.013) and inversely correlated with
patient disease-free survival rates (p = 0.005). Expression of flotillin-1 was
associated with H-Ras in breast cancer, especially in TNBC (p < 0.001). Our
findings provide insight into the molecular basis of Ras isoform-specific
interplay with flotillin-1, leading to tumorigenicity and aggressiveness of
breast cancer.
PMID- 26413936
TI - Effect of the laser pulse width on the field evaporation behavior of metals and
oxides.
AB - The laser assisted field-evaporation of metals and oxides strongly depends on the
illumination conditions. Here we study the effect of laser pulse width using two
different laser systems, with a pulse duration of a few tens of femtoseconds and
a few tens of picoseconds, respectively. Adjusting the laser wavelength by
nonlinear optical conversion systems, we study the evaporation behavior of FeCu
and MgO samples. We prove that the laser pulse width does not affect the
evaporation behavior, in the range of duration explored. These results are
explained taking into account the absorption behavior of nanometric samples and
their thermal properties.
PMID- 26413937
TI - Self-adapting denoising, alignment and reconstruction in electron tomography in
materials science.
AB - An automatic procedure for electron tomography is presented. This procedure is
adapted for specimens that can be fashioned into a needle-shaped sample and has
been evaluated on inorganic samples. It consists of self-adapting denoising,
automatic and accurate alignment including detection and correction of tilt axis,
and 3D reconstruction. We propose the exploitation of a large amount of
information of an electron tomography acquisition to achieve robust and automatic
mixed Poisson-Gaussian noise parameter estimation and denoising using undecimated
wavelet transforms. The alignment is made by mixing three techniques, namely (i)
cross-correlations between neighboring projections, (ii) common line algorithm to
get a precise shift correction in the direction of the tilt axis and (iii)
intermediate reconstructions to precisely determine the tilt axis and shift
correction in the direction perpendicular to that axis. Mixing alignment
techniques turns out to be very efficient and fast. Significant improvements are
highlighted in both simulations and real data reconstructions of porous silicon
in high angle annular dark field mode and agglomerated silver nanoparticles in
incoherent bright field mode. 3D reconstructions obtained with minimal user
intervention present fewer artefacts and less noise, which permits easier and
more reliable segmentation and quantitative analysis. After careful sample
preparation and data acquisition, the denoising procedure, alignment and
reconstruction can be achieved within an hour for a 3D volume of about a hundred
million voxels, which is a step toward a more routine use of electron tomography.
PMID- 26413938
TI - Recovery of Olfactory Function following Pediatric Traumatic Brain Injury: A
Longitudinal Follow-Up.
AB - There is increasing evidence that disruption of olfactory function after
pediatric traumatic brain injury (TBI) is common. Olfactory dysfunction (OD) has
been linked to significant functional implications in areas of health, safety,
and quality of life, but longitudinal research investigating olfactory recovery
is limited. This study aimed to investigate recovery trajectories for olfaction
following pediatric TBI and explore predictors of early and late olfactory
outcomes. The olfactory function of 37 children with TBI ages 8-16 years was
assessed on average at 1.5, 8.0, and 18.0 months post-injury using the University
of Pennsylvania Smell Identification Test. A significant improvement in olfactory
performance was seen over time in those with acute OD, however, only 16% of those
with the most severe OD showed recovery to normal olfactory function, with the
remainder demonstrating ongoing olfactory impairment at the 18 month follow-up.
Predictors of early (0-3 month) and late (18 month) olfactory outcomes varied
with site of impact, a significant predictor of later olfactory performance. In
summary, while there was evidence of recovery of OD over time in pediatric TBI,
the majority of children with severe OD did not show any recovery. In light of
limited recovery of function for more severely affected children, the importance
of appropriate education and implementation of rehabilitation management
strategies is highlighted.
PMID- 26413939
TI - Biomechanical Evaluation of the Stabilizing Function of Three Atlantoaxial
Implants Under Shear Loading: A Canine Cadaveric Study.
AB - OBJECTIVE: To compare the biomechanical properties of a ventral transarticular
lag screw fixation technique, a new dorsal atlantoaxial instability (AAI) clamp,
and a new ventral AAI hook plate under sagittal shear loading after transection
of the ligaments of the atlantoaxial joint. STUDY DESIGN: Cadaveric biomechanical
study. ANIMALS: Canine cadavers (n = 10). MATERIALS AND METHODS: The
occipitoatlantoaxial region of Beagles euthanatized for reasons unrelated to the
study was prepared leaving only ligamentous structures and the joint capsules
between the first 2 cervical vertebrae (C1 and C2). The atlanto-occipital joints
were stabilized with 2 transarticular diverging positive threaded K-wires. The
occipital bone and the caudal end of C2 were embedded in polymethylmethacrylate
and loaded in shear to a force of 50 Newtons. The range of motion (ROM) and
neutral zone (NZ) of the atlantoaxial joint were determined after 3 loading
cycles with atlantoaxial ligaments intact, after ligament transection, and after
fixation with each implant. The testing order of implants was randomly assigned.
The implants tested last were subjected to failure testing. RESULTS: All
stabilization procedures decreased the ROM and NZ of the atlantoaxial joint
compared to transected ligament specimens. Only stabilization with transarticular
lag screws and ventral plates produced a significant reduction of ROM compare to
intact specimens. CONCLUSION: Fixation with transarticular lag screws and a
ventral hook plate was biomechanically similar and provided more rigidity
compared to dorsal clamp fixation. Further load cycling to failure tests and
clinical studies are required before making clinical recommendations.
PMID- 26413942
TI - The Trustworthiness Deficit in Postgenomic Research on Human Intelligence.
AB - In the past, work on racial and ethnic variation in brain and behavior was
marginalized within genetics. Against the backdrop of genetics' eugenic legacy,
wide consensus held such research to be both ethically problematic and
methodologically controversial. But today it is finding new opportunistic venues
in a global, transdisciplinary, data-rich postgenomic research environment in
which such a consensus is increasingly strained. The postgenomic sciences display
worrisome deficits in their ability to govern and negotiate standards for making
postgenomic claims in the transdisciplinary space between human population
variation research, studies of intelligence, neuroscience, and evolutionary
biology. Today some researchers are pursuing the genomics of intelligence on a
newly grand scale. They are sequencing large numbers of whole genomes of people
considered highly intelligent (by varying empirical and social measures) in the
hope of finding gene variants predictive of intelligence. Troubling and at times
outlandish futurist claims accompany this research. Scientists involved in this
research have openly discussed the possibility of marketing prenatal tests for
intelligence, of genetic engineering or selective embryo implantation to increase
the likelihood of a high-IQ child, and of genotyping children to guide their
education. In this permissive and contested environment, what would trustworthy
research on the genomics of high intelligence look like?
PMID- 26413943
TI - An Introduction to Thinking about Trustworthy Research into the Genetics of
Intelligence.
AB - The advent of new technologies has rekindled some hopes that it will be possible
to identify genetic variants that will help to explain why individuals are
different with respect to complex traits. At least one leader in the development
of "whole genome sequencing"-the Chinese company BGI-has been quite public about
its commitment to using the technique to investigate the genetics of intelligence
in general and high intelligence in particular. Because one needs large samples
to detect the small effects associated with small genetic differences in the
sequence of those base pairs, to make headway with the new sequencing
technologies, one also needs to enlist much larger numbers of study participants
than geneticists have enrolled before. In an effort to increase the size of a
sample, one team of researchers approached the Center for Talented Youth at Johns
Hopkins University. They wanted to gain access to records concerning participants
in CTY's ongoing Study of Exceptional Talent, and they wanted to approach those
individuals to see if they would be willing to share samples of their DNA. We
agreed that CTY's dilemma about whether to give the researchers access to those
records raised larger questions about the ethics of research into the genetics of
intelligence, and we decided to hold a workshop at The Hastings Center that could
examine those questions. Our purpose was to create what, borrowing from Sarah
Richardson, we came to call a "transformative conversation" about research into
the genetics of general cognitive ability-a conversation that would take a wide
and long view and would involve a diverse group of stakeholders, including both
people who have been highly critical of the research and people who engage in it.
This collection of essays, which grew out of that workshop, is intended to
provide an introduction to and exploration of this complex and important area.
PMID- 26413944
TI - General Intelligence (g): Overview of a Complex Construct and Its Implications
for Genetics Research.
AB - Current technology has dramatically increased the prevalence of studies to
establish the genetic correlates of a wide variety of human characteristics,
including not only the physical attributes that determine what we look like and
the risk of physiological disease but also the psychological and cognitive
characteristics that often define who we are as individuals. Perhaps one of the
most deeply personal and often controversial characteristics is the concept of
general intelligence, known in the psychological literature as "g." As with the
genetic study of any complex trait, the first step in studying the genetics of g
is to carefully define the characteristic of interest. For g, this entails
establishing what intelligence means and providing a clear operational definition
for how it will be measured. In this paper, we provide a brief historical and
theoretical overview of the construct of general intelligence, describe its
relationship to the contemporary measurement of intelligence, and discuss these
concepts in light of the challenges associated with defining g as a
characteristic in the study of genetics.
PMID- 26413945
TI - Classical and Molecular Genetic Research on General Cognitive Ability.
AB - Arguably, no psychological variable has received more attention from behavioral
geneticists than what has been called "general cognitive ability" (as well as
"general intelligence" or "g"), and for good reason. GCA has a rich correlational
network, implying that it may play an important role in multiple domains of
functioning. GCA is highly correlated with various indicators of educational
attainment, yet its predictive utility is not limited to academic achievement. It
is also correlated with work performance, navigating the complexities of everyday
life, the absence of various social pathologies (such as criminal convictions),
and even health and mortality. Although the causal basis for these associations
is not always known, it is nonetheless the case that research on GCA has the
potential to provide insights into the origins of a wide range of important
social outcomes. In this essay, our discussion of why GCA is considered a
fundamentally important dimension of behavior on which humans differ is followed
by a look at behavioral genetics research on CGA. We summarize behavioral
genetics research that has sought to identify and quantify the total
contributions of genetic and environmental factors to individual differences in
GCA as well as molecular genetic research that has sought to identify genetic
variants that underlie inherited effects.
PMID- 26413946
TI - Genetic Prediction.
AB - The fundamental reason that the genetics of behavior has remained so
controversial for so long is that the layer of theory between data and their
interpretation is thicker and more opaque than in more established areas of
science. The finding that variations in tiny snippets of DNA have small but
detectable relations to variation in behavior surprises no one, at least no one
who was paying attention to the twin studies. How such snippets of DNA are
related to differences in behavior-known as the gene-to-behavior pathway-is the
great theoretical problem of modern behavioral genetics. Given that intentional
human breeding is a horrific prospect, what kind of technology might we want (or
fear) out of human behavioral genetics? One possibility is a technology that
could predict important behavioral characteristics of humans based on their
genomes alone. A moment's thought suggests significant benefits and risks that
might be associated with such a possibility, but for the moment, just consider
how convincing it would be if on the day of a baby's birth we could make
meaningful predictions about whether he or she would become a concert pianist or
an alcoholic. This article will consider where we are right now as regards that
possibility, using human height and intelligence as the primary examples.
PMID- 26413947
TI - Can Genetics Research Benefit Educational Interventions for All?
AB - Pretty much everyone knows that our genes have at least something to do with how
able or how high achieving we are. Some believe that we should not speak of this
common knowledge, nor inquire into how genetic influence works or what it might
mean. If we do not keep an open mind to the fact of genetic influence on academic
achievement, however, then we cannot explore its possible implications. And if we
do not consider the implications, then we cannot, as a society, harness any
potential benefits or avoid possible pitfalls. So that's what this essay is about
exploring what behavioral genetics research might be able to offer to educational
theory, policy, and practice. We cannot yet use biological information to make
accurate predictions for all children. We do know, however, that academic
achievement is heritable, which is to say that differences between individuals
are influenced by differences in their DNA. If genes are part of the problem for
some pupils (to take the negative spin on this), then it seems likely that
studying them could be part of a solution. And that's what behavioral geneticists
are trying to do-to chart and understand pathways from DNA to behavior and to
identify interventions that can maximize outcomes for all. The fact is, though,
that we have an awfully long way to go.
PMID- 26413948
TI - What Does Behavioral Genetics Offer for Improving Educaton?
AB - For much of its history, behavioral genetics, or research into the influence
genetics has on human behavior, has been associated with a pessimistic view of
educational reforms' potential to make much difference in improving educational
outcomes or reducing inequality. Recently, however, some behavioral geneticists
have begun to speak in more optimistic terms about the promise of genetically
informed education to improve learning for all children, especially those who are
socially or economically disadvantaged. This shift in emphasis should be welcome
news for everyone interested in promoting educational improvement who worried
that behavioral genetics offered support for the status quo. However, I think it
amounts to little more than a shift in tone. Behavioral genetics, I will argue,
does not advance educational reform: its proposed solutions are rooted in the
limits, not the strength, of behavioral genetics knowledge; repeat the ideas of
earlier U.S. educational reform efforts; and rely on a naive optimism about the
power of choice and personalization.
PMID- 26413949
TI - Can Research on the Genetics of Intelligence Be "Socially Neutral"?
AB - The history of research on the genetics of intelligence is fraught with social
bias. During the eugenics era, the hereditary theory of intelligence justified
policies that encouraged the proliferation of favored races and coercively
stemmed procreation by disfavored ones. In the 1970s, Berkeley psychologist
Arthur Jensen argued that black students' innate cognitive inferiority limited
the efficacy of federal education programs. The 1994 controversial bestseller The
Bell Curve, by Richard J. Herrnstein and Charles Murray, rehashed the claim that
race and class disparities stem from immutable differences in inherited
intelligence, which could not be eliminated through social interventions. Today
most scientists studying the genetics of intelligence distance themselves from
this history of social bias by arguing that their research need not investigate
intellectual differences between social groups. Rather, they argue, examining the
heritability of intelligence can be socially neutral and may even help to reduce
social inequities. I argue, however, that research on the genetics of
intelligence cannot be socially neutral. Even if we divorce the heritability of
intelligence from a eugenicist mission, measuring intelligence remains useful
only as a gage of individuals' appropriate positions in society. Research into
the genetics of intelligence ultimately helps to determine individuals' inherited
capacity for particular social positions, even when researchers aim to modify the
effects of inheritance.
PMID- 26413950
TI - Taking a Stand: The Genetics Community's Responsibility for Intelligence
Research.
AB - There is a longstanding debate about genetics research into intelligence. Some
scholars question the value of focusing on genetic contributions to intelligence
in a society where social and environmental determinants powerfully influence
cognitive ability and educational outcomes. Others warn that censoring certain
research questions, such as inquiries about genetic differences in intellectual
potential, compromises academic freedom. Still others view interest in this
subject as a corollary to a long and troublesome history of eugenics research.
The dawn of a new era in genome sequencing as a commodity will sustain scientific
interest in the genetics of intelligence for the foreseeable future, but deep
rooted challenges threaten the scientific merit of the research. The use of
imprecise definitions of study populations, the difficult nature of studying the
environment, and the potential of researcher bias are inextricably linked with
concerns about the trustworthiness and utility of research in this area.
Leadership by the genetics community is essential to ensure the value and
trustworthiness of these studies.
PMID- 26413951
TI - Trustworthy Research Institutions: The Challenging Case of Studying the Genetics
of Intelligence.
AB - It is simple enough to claim that academic research institutions ought to be
trustworthy. Building the culture and taking the steps necessary to earn and
preserve institutional trust are, however, complex processes. The experience
motivating this special report--a request for the Center for Talented Youth at
Johns Hopkins University to collaborate on research regarding the genetics of
intelligence--illustrates how ensuring institutional trustworthiness can be in
tension with a commitment to fostering research. In this essay, we explore the
historical context for biomedical research institutions like Johns Hopkins that
have worked to build local community trust. In so doing, we consider how the
example under focus in this special report can lead to greater consideration of
how research institutions balance fostering trust with their other commitments.
PMID- 26413952
TI - Obligations and Concerns of an Organization Like the Center for Talented Youth.
AB - There is another set of entities that needs to be brought into the conversation
about the ethical, legal, and social implications of scientific conduct. This
widely varied group includes not-for-profit educational, academic, public
service, and philanthropic organizations other than the type mentioned above as
well as for-profit businesses. Despite their major differences, these
organizations may all be in a position to make decisions, directly or indirectly,
about the conduct of scientific research. And those decisions may have a
significant impact on the parties normally involved in thinking and talking about
obligations and concerns-the researchers, the subjects, and the general public.
Yet there are few if any conceptual frameworks to help organizations address the
ethical, legal, and social issues related to conducting scientific research.
There are also few resources to help organizations find and develop the expertise
required to make responsible decisions or communicate those decisions in ways
that could support and advance the ethical conduct of research. In what follows,
we try to identify and explore the duties, rights, and interests of one such
organization, the Center for Talented Youth at Johns Hopkins University, when
asked to play a supporting role in research on the genetics of intelligence. As
central agents in this case, we hope to demonstrate why organizations like CTY
cannot be neglected in the broader effort to ensure trustworthy research into the
genetics of intelligence.
PMID- 26413953
TI - Why Is Studying the Genetics of Intelligence So Controversial?
AB - From the very beginning, studies of the nature and nurture of intelligence have
been closely associated with an interest in intervening, and those interventions
have been surrounded by controversy. The nature of those controversies has not
always been the same, however. Since the mid-nineteenth century, when Francis
Galton imagined a science that would assess the extent to which a trait like
"genius" was due to nature or due to nurture, science and technology have changed
dramatically, and so have the interventions that have been envisioned in light of
those developments. A scientist today can search for particular stretches of DNA
and assess whether differences in those stretches are associated with differences
in a human trait of interest; a genetic counselor today can genetically test an
individual (be it an embryo, fetus, newborn, child, or adult) and provide
information about what that genetic result means, allowing for interventions that
can range from terminating a pregnancy to prescribing chemotherapy. So when one
asks a question like, "Why is studying the genetics of intelligence
controversial?," it is important to realize up front that the answer will be, "It
can be controversial for a variety of different reasons, and those reasons have
evolved over time." The purpose of this essay is to provide a survey of the
controversies that surround genetic studies of intelligence. With the survey in
place, I will then draw out several lessons both for scientists who study the
genetics of intelligence as well as for science studies scholars (bioethicists,
philosophers, historians, sociologists) who reflect and comment on the
controversies surrounding that research.
PMID- 26413954
TI - A critical review of low-carbohydrate diets in people with Type 2 diabetes.
AB - AIMS: The efficacy of low-carbohydrate diets (LCD) in people with Type 2 diabetes
has divided the nutrition community. This review seeks to re-examine the
available data to clarify understanding. METHODS: A comprehensive search of
databases was used to identify meta-analyses of LCD in Type 2 diabetes. To
improve the quality of the studies analysed, the following inclusion criteria
were applied: randomized control trials >= 4 weeks in people aged > 18 years with
Type 2 diabetes; a carbohydrate intake <= 45% of total energy intake per day; and
a dietary intake assessment at the end of the study. The resulting studies were
subjected to a thematic analysis. RESULTS: Nine meta-analyses were identified
containing 153 studies. Twelve studies met our amended inclusion criteria. There
were no significant differences in metabolic markers, including glycaemic
control, between the two diets, although weight loss with a LCD was greater in
one study. Carbohydrate intake at 1 year in very LCD (< 50 g of carbohydrates)
ranged from 132 to 162 g. In some studies, the difference between diets was as
little as 8 g/day of carbohydrates. CONCLUSION: Total energy intake remains the
dietary predictor of body weight. A LCD appears no different from a high
carbohydrate diet in terms of metabolic markers and glycaemic control. Very LCDs
may not be sustainable over a medium to longer term as carbohydrate intake in
diets within studies often converged toward a more moderate level. The variable
quality of studies included in earlier meta-analyses likely explains the previous
inconsistent findings between meta-analyses.
PMID- 26413957
TI - Comparison of Subciliary Approaches in Orbito-Zygomatic Fractures: Skin Flap
Versus Skin-Muscle Flap.
AB - BACKGROUND: Because of the complications of classical subciliary incision, some
modified subciliary approaches have been described in recent literature.
OBJECTIVES: The aim of this study was to compare 2 commonly used subciliary
approaches according to development of postoperative complications (scar
formation, and ectropion). MATERIALS AND METHODS: Ninety patients were included
in this retrospective study. Subciliary skin flap technique (SF group) was
performed to 39 patients, while the others were operated by using skin-muscle
(stepped) flap technique (SMF group). Fitzpatrick skin types, genders, ages, scar
scores, and ectropion scores of the patients also were recorded. RESULTS: The
mean age of the patients was 39.3 (18-99) years, and the mean follow-up period
was 2.1 (1-6) years. Fitzpatrick skin-type levels were between 2 and 4 (median =
3). No difference was found between 2 groups in terms of age, follow-up period,
and Fitzpatrick skin-type levels. However, the scar values of the SMF group were
significantly lower than the SF group statistically. Also, there was no
significant difference between males and females in SF and SMF groups in terms of
scar and ectropion formation. On the other hand, scar values were lower in SMF
groups rather than SF group in males. Although ectropion values were not
different between SF and SMF groups in females, ectropion values of SMF group
were significantly lower than SF group in males statistically. CONCLUSION:
Subciliary skin-muscle (stepped) flap technique can be more reliable than
subciliary skin flap technique for approach to orbitozygomatic fractures.
PMID- 26413958
TI - Cleft Patient-Reported Postoperative Donor Site Pain Following Alveolar
Autologous Iliac Crest Bone Grafting: Comparing Two Minimally Invasive Harvesting
Techniques.
AB - BACKGROUND: Autologous bone grafting is still considered the standard method for
alveolar cleft repair. However, donor site morbidities remain a relevant problem
in cleft care. Thus, the authors assessed postoperative donor site pain in cleft
patients who underwent alveolar cleft repair by iliac crest bone graft
transferring through a prospective randomized study comparing 2 minimally
invasive harvesting techniques. METHODS: Fifty-six consecutive patients with
cleft lip and palate who underwent iliac crest bone grafting for alveolar cleft
repair were randomly divided into 2 groups: bone graft harvested by minimally
invasive techniques without (group 1) and with (group 2) periosteum elevation.
Postoperative donor site pain was evaluated using a unidimensional numerical pain
intensity rating scale (0, "no pain;" 10, "worst pain imaginable") at 1, 3, 6, 9,
and 12 hours after the procedures and on the 3rd, 7th, 14th, 21st, and 28th days
after surgeries. Intergroup comparisons were performed. RESULTS: The mean
measurements of donor site pain revealed no significant differences (all P >
0.05) in any of the evaluated postoperative period comparisons between groups 1
and 2. There was a greater number (P < 0.05) of group 1 patients who reported "no
pain" in the donor site compared with group 2, suggesting that periosteum
elevation may play a role in pain intensity measurement. CONCLUSIONS: This
prospective randomized study showed no difference in pain intensity among cleft
patients who had postoperative pain. However, a greater number of patients in
group 1 reported "no pain" in comparison to patients in group 2.
PMID- 26413959
TI - Pseudomeningocele With Orbital Extension as a Complication of Fronto-Orbital
Advancement and Remodeling in Craniosynostosis.
AB - AIM: The authors present a series of patients who developed a pseudomeningocele
following fronto-orbital advancement and remodeling (FOAR), describing clinical
presentation, investigations, and management. Risk factors are identified and
preventative strategies suggested. MATERIALS AND METHODS: From 2002 to 2012, all
patients who underwent FOAR at our unit were identified. Those who developed a
pseudomeningocele were selected and case notes, scan imaging and photographs were
reviewed. RESULTS: Two hundred thirty-six FOAR operations were carried out over
12 consecutive years. Sixty-one of these patients were syndromic. A
pseudomeningocele occurred in 6 patients. All affected cases were syndromic.
Clinical features of presentation with orbital pseudomeningocele included orbital
swelling, ptosis, proptosis, and/or hypoglobus. Raised intracranial pressure
(ICP) was managed before pseudomeningocele repair in 2 patients, at the time of
pseudomeningocele repair using an extra-ventricular drain (EVD) or lumbar drain
in 4 patients. Decompression of the pseudomeningocele with excision and duraplsty
was carried out in 5 patients, 1 patient required excision of gliotic brain and
obliteration of dead space. Four patients had a calvarial graft to manage the
bony defect and a further 2 had a titanium mesh. None of the patients had a
recurrence of the pseudomeningocele or any long-term ocular or aesthetic
complications. CONCLUSION: Pseudomeningocele has not previously been described in
FOAR, but in a large series of consecutive patients, we have identified a 2.5%
incidence. This incidence increases to 10% in the syndromic population of
patients undergoing FOAR. The risk factors include a diagnosis of syndromic
craniosynostosis, dural tear, hydrocephalus or raised ICP, infection, persistent
cerebrospinal fluid (CSF) leak, or presence of dead space. Preventative
strategies include CSF management before or post-FOAR. The ultimate treatment of
the pseudomeningocele and growing fracture involves surgical decompression of the
collection, a duraplasty, reconstruction of the orbital roof, and temporary CSF
diversion.
PMID- 26413960
TI - Analysis of Long-Term Prognosis and Prognostic Predictors in Severe Brain Injury
Patients Undergoing Decompressive Craniectomy and Standard Care.
AB - Decompressive craniectomy (DC) is widely used to treat acute subdural haematoma
and hemispheric swelling following traumatic brain injury (TBI). The therapeutic
effect of DC on severe TBI treatment is still controversial. The aim of our study
was to evaluate effectiveness of DC treatment and seek some prognostic
predictors. According to the therapy method, we divided the patients into 2
groups: DC group and standard care group. Between 2010 and 2014, a total number
of 223 severe TBI patients, containing 112 patients undergoing DC and 111
patients undergoing standard care, were enrolled into the study according to
Glasgow Coma Scale (GCS). The long-term prognosis was evaluated by Extended
Glasgow Outcome Scale 12 months after discharging from hospital. We used
univariate analysis and receiver operating characteristic curves to explore
prognostic predictors. The results showed that patients in the DC group had a
lower mortality, but there was no statistical significance in long-term prognosis
between these 2 groups. It seemed that admission GCS, platelet, neutrophile
granulocyte, total protein, and albumin were associated with long-term prognosis
in DC group and reactivity of pupils in standard care group. Simultaneously,
using the multivariable logistic regression model, we confirmed that admission
GCS and albumin were independent prognostic predictors for patients undergoing
DC, and reactivity of pupils for those undergoing standard care. Our data
suggested that DC was an effective therapy for severe TBI patients in reducing
mortality, but it failed to improve long-term prognosis. Through our study, we
could comprehend the characteristics of the 2 treatments and provide more
scientific individuation therapy for severe TBI patients.
PMID- 26413961
TI - Clinical and Radiologic Characteristics of Inferior Rectus Muscle Sheath
Entrapment in Orbital Blowout Fracture.
AB - Blowout fracture is a common condition in the oculoplastics clinic. One of the
indications for its repair is entrapment of the inferior rectus muscle within the
fracture site. Herein, the authors present 3 patients of inferior rectus muscle
sheath entrapment without entrapment of the muscle itself. The outcome of
treatment was excellent in all patients. The aim of this report is to present the
special clinical and radiologic findings in such patients.
PMID- 26413962
TI - Comparison Between Continuous Buried Suture and Interrupted Buried Suture Methods
for Double Eyelid Blepharoplasty.
AB - PURPOSE: The objective of this study was to compare the surgical outcomes between
interrupted and continuous buried suture methods in double eyelid blepharoplasty
in Koreans. METHODS: Medical records of 204 patients (392 eyes) who underwent
double eyelid operation by buried suture method and who were followed up for at
least more than 3 months were reviewed. Patients were divided into 2 groups
according to the buried suture method; an interrupted group (88 patients) and a
continuous group (116 patients). RESULTS: The rate of loss of formed double
eyelid is 19.3 % (17 of 88 patients) in interrupted buried method and 8.6 % (10
of 116 patients) in continuous group (P = 0.026). One patient experienced an
exposure of suture knot in a continuous group, whereas 5 patients experienced an
exposure of suture knot and 1 patient suffered from granuloma in an interrupted
group (P = 0.021). CONCLUSIONS: The continuous buried suture method has a lower
rate of the loss of double folds and less complication than the interrupted
buried suture method for double fold formation in Koreans.
PMID- 26413963
TI - Communications Between the Facial Nerve and the Vestibulocochlear Nerve, the
Glossopharyngeal Nerve, and the Cervical Plexus.
AB - The aim of this review is to elucidate the communications between the facial
nerves or facial nerve and neighboring nerves: the vestibulocochlear nerve, the
glossopharyngeal nerve, and the cervical plexus.In a PubMed search, 832 articles
were searched using the terms "facial nerve and communication." Sixty-two
abstracts were read and 16 full-text articles were reviewed. Among them, 8
articles were analyzed.The frequency of communication between the facial nerve
and the vestibulocochlear nerve was the highest (82.3%) and the frequency of
communication between the facial nerve and the glossopharyngeal nerve was the
lowest (20%). The frequency of communication between the facial nerve and the
cervical plexus was 65.2 +/- 43.5%. The frequency of communication between the
cervical branch and the marginal mandibular branch of the facial nerve was 24.7
+/- 1.7%.Surgeons should be aware of the nerve communications, which are
important during clinical examinations and surgical procedures of the facial
nerves such as those communications involved in facial reconstructive surgery,
neck dissection, and various nerve transfer procedures.
PMID- 26413964
TI - Do Pharyngeal Surgeries for Snoring and Obstructive Sleep Apnea Have an Impact on
Nasalance Scores?
AB - OBJECTIVE: Most of the surgeries which are used in the treatment of habitual
snoring and obstructive sleep apnea (OSA) mainly target velopharyngeal
structures, which play an important role in voice characteristics such as
nasalance. The aim of this study is to assess the effect of different types of
such surgical procedures including expansion sphincter pharyngoplasty (ESP),
lateral pharyngoplasty (LP), and anterior palatoplasty (AP) on nasalance scores.
SUBJECTS AND METHODS: Forty-nine consecutive patients with primary snoring or OSA
who underwent AP, LP, and ESP procedures were included in this study. All
patients underwent a fully attended overnight polysomnography and detailed
otolaryngologic examination. Nasalance studies were performed with Nasometer II
instrument (model 6400; Kay Elemetrics, Lincoln Park, NJ) by reading 3 passages
that were categorized according to the amount of nasal consonants (oral, oro
nasal, and nasal passages), preoperatively, and 3 months after surgery. RESULTS:
There was no statistically significant difference in either group between
preoperative and postoperative assessments of nasalance scores for all 3
passages. Seven patients experienced nasal regurgitation symptoms for fluids for
a short time after LP, 2 patients after AP, and 7 patients after ESP. None of
these symptoms showed persistence and diminished approximately at 1-month follow
up. CONCLUSION: Anterior palatoplasty, LP, and ESP seem not to have any impact on
nasalance scores of males.
PMID- 26413965
TI - Congenital Melanocytic Nevus of the Nose Removed Using Dermabrasion,
Hydroquinone, and Serial Excision.
AB - We report a child with a congenital pigmented nevus of the nose involving the
left ala, sidewall, soft triangle, and tip. Removal of the lesion was performed
using dermabrasion, topical hydroquinone, and serial excision to optimize the
aesthetic outcome. The patient was left with a linear scar and did not require
reconstruction with a skin graft or flap.
PMID- 26413966
TI - Incidence and Features of Vertebral Fractures After Scalp Avulsion Injuries.
AB - BACKGROUND: Scalp injuries are usually extensive and may have a deleterious
impact for the patient. To date, little is known in the literature about
simultaneous vertebral fractures. The aim of this study was to analyze the
frequency, features and pathogenesis of vertebrae fractures after scalp avulsion
injuries. METHODS: Between 2004 and 2014, 64 patients were retrospectively
identified after scalp avulsion injuries. Patient records were reviewed for
mechanism of trauma, clinical examination and neurological deficits. The features
of vertebral fractures were evaluated by X-ray, computed tomography or magnetic
resonance imaging, where necessary. Various treatment options were evaluated
according to their injuries. RESULTS: Totally, 6 women (9.4%) with a mean age 37
+/- 6 years were identified with cervical fractures due to scalp avulsion
injuries (mean size defect 808 +/- 56 cm). Clinical examination revealed
neurological deficits in 3 patients. Five patients were diagnosed with different
types of C2 fracture and 1 patient was diagnosed with C7 fracture. One patient
had simultaneous fractures of T3/T4. Treatment for the scalp avulsion consisted
in either composite graft in 5 patients or microsurgical replantation in 1
patient. The vertebral fractures were treated by collar protection (3), cervical
traction (1), HALO fixation (1), and internal stabilization (1), respectively.
CONCLUSIONS: Most vertebral fractures associated with scalp avulsion injuries are
C2 fractures. Careful and appropriate examination is mandatory for patients with
scalp avulsion injuries to exclude vertebral fractures which, if not recognized
early, can have serious and devastating consequences.
PMID- 26413967
TI - Recurrent Cricopharyngeal Achalasia in a Child With Williams-Beuren Syndrome.
PMID- 26413968
TI - Isolated Congenital Partial Absence of the Lateral Crural Cartilage.
PMID- 26413969
TI - Polymorphous Low-Grade Adenocarcinoma of the Oral Cavity.
PMID- 26413970
TI - Solitary Neurofibroma Originating From the Nasal Septum.
PMID- 26413971
TI - Complete Removal of External Nasal Neurofibroma by Endonasal Approach.
AB - Although neurofibroma can develop in every possible anatomic location,
neurofibroma originating from the external nose is extremely rare, and to our
knowledge, only 2 cases have been reported so far in the English literature. In
this report, the authors experienced a solitary neurofibroma originating from the
external nose, which was successfully removed by endonasal approach (marginal
incision).
PMID- 26413972
TI - Tetrodotoxin detection and species identification of pufferfish in retail roasted
fish fillet by DNA barcoding in China.
AB - This study identifies the pufferfish species and detects tetrodotoxin (TTX) in
roasted fish fillet samples collected in Beijing, Qingdao and Xiamen, China. The
cytochrome c oxidase I (COI) gene was used as the target gene for identification
of the pufferfish species in the samples. Enzyme-linked immunosorbent assay
(ELISA) screened the TTX levels in samples that had been detected as containing
pufferfish by DNA barcode. A total of 125 samples were identified by DNA
barcodes; 32 (26%) samples contained pufferfish composition and, among them, 26
(81%) were the highly toxic species Lagocephalus lunaris. All 32 samples
containing the pufferfish composition were positive for TTX with levels ranging
from 100 to 63,800 ng g(-1). Most of the 32 samples contained the highly toxic L.
lunaris. Based on the results, we suggest that the monitoring of roasted fish
fillet should be strengthened and the processing procedures should be
standardised to minimise TTX poisoning caused by pufferfish.
PMID- 26413973
TI - An easy-to-prepare mini-scaffold for DNA origami.
AB - The DNA origami strategy for assembling designed supramolecular complexes
requires ssDNA as a scaffold strand. A system is described that was designed
approximately one third the length of the M13 bacteriophage genome for ease of
ssDNA production. Folding of the 2404-base ssDNA scaffold into a variety of
origami shapes with high assembly yields is demonstrated.
PMID- 26413974
TI - Straightforward Generation of Pillared, Microporous Graphene Frameworks for Use
in Supercapacitors.
AB - Microporous, pillared graphene-based frameworks are generated in a simple
functionalization/coupling procedure starting from reduced graphene oxide. They
are used for the fabrication of high-performance supercapacitor devices.
PMID- 26413975
TI - Therapeutic application of mesenchymal stem cells in osteoarthritis.
AB - INTRODUCTION: Osteoarthritis (OA) is a degenerative disease characterized by
cartilage degradation and subchondral bone alterations. This disease represents a
global public health problem whose prevalence is rapidly growing with the
increasing aging of the population. With the discovery of mesenchymal stem cells
(MSC) as possible therapeutic agents, their potential for repairing cartilage
damage in OA is under investigation. AREAS COVERED: Characterization of MSCs and
their functional properties are mentioned with an insight into their trophic
function and secretory profile. We present a special focus on the types of
extracellular vesicles (EVs) that are produced by MSCs and their role in the
paracrine activity of MSCs. We then discuss the therapeutic approaches that have
been evaluated in pre-clinical models of OA and the results coming out from the
clinical trials in patients with OA. EXPERT OPINION: MSC-based therapy seems a
promising approach for the treatment of patients with OA. Further research is
still needed to demonstrate their efficacy in clinical trials using controlled,
prospective studies. However, the emergence of MSC-derived EVs as possible
therapeutic agents could be an alternative to cell-based therapy.
PMID- 26413976
TI - Facile synthesis of nano-sized agarose based amino acid-Its pH-dependent protein
like behavior and interactions with bovine serum albumin.
AB - In a facile synthesis agarose was amphoterically functionalized to afford nano
sized agarose amino acids, aminoagarose succinate half-esters (AAE) containing
one pendant carboxyl group. Nano-sized AAEs (<10 nm; DLS) were characterized and
they had three various degrees of substitution [overall DSs 0.88, 0.89 and 0.96],
both the amino and half-ester groups were placed on C-6 positions of the 1,3 beta
d-galactopyranose moieties of agarose backbone ((13)C NMR). AAEs performed like
large protein molecules exhibiting pH-responsive structural variations (optical
rotatory dispersion), presenting a mixed solubility pattern like random coil
(soluble) and aggregate (precipitation) formations. Circular dichroism studies
showed their pH-dependent associative interactions with bovine serum albumin,
which indicated complexation at acidic and basic pHs, and decomplexation at pH
6.8 with AAE (DS 0.96). Thus, these nano-sized AAE based systems may be of
potential utility in the domains demanding the merits of preferential protein
bindings e.g. pH-responsive cationic/anionic drug carrier, separations or chiral
sensing applications.
PMID- 26413977
TI - Preameloblast-Derived Factors Mediate Osteoblast Differentiation of Human Bone
Marrow Mesenchymal Stem Cells by Runx2-Osterix-BSP Signaling.
AB - Epithelial-mesenchymal interaction occurs during development of various tissues,
including teeth and bone. Recently, a preameloblast-conditioned medium (PA-CM)
from mouse apical bud cells (ABCs), a type of dental epithelial cell, was found
to induce odontogenic differentiation of dental pulp stem cells and promote
dentin formation. The aims of the present study were to investigate the effects
of PA-CM on human bone marrow mesenchymal stem cells (hBMSCs) in vitro, and to
investigate the bone regenerative capacity in vivo through epithelial-mesenchymal
interactions of developmental osteogenesis. Coculturing with ABCs and PA-CM
treatment upregulated osteoblast differentiation markers of hBMSCs compared to
cells cultured alone. PA-CM accelerated mineralized nodule formation and also
increased bone sialoprotein promoter activity in hBMSCs. PA-CM facilitated the
migration of hBMSCs, but did not significantly influence proliferation. PA-CM
promoted bone formation of hBMSCs in vivo. Radiographic and histologic findings
showed that PA-CM induced the bony regeneration at calvarial defects in rat.
Taken together, these data show that PA-CM enhances the migration and osteogenic
differentiation of hBMSCs in vitro and induces bone formation in vivo.
PMID- 26413980
TI - Small-to-moderate decreases in cold hypersensitivity up to 3 years after severe
hand injuries: A prospective cohort study.
AB - BACKGROUND: The natural course and predictors for decreased cold hypersensitivity
were studied in 85 patients with severe hand injuries involving nerve lesions.
METHODS: Questionnaires including the McCabe Cold Sensitivity Severity scale (CSS
0-400) were collected after injury, and at 6-month, 12-month, 2-year, and 3-year
follow-ups. RESULTS: Between the 12-month and 3-year follow-up, there was a small
decrease in cold hypersensitivity as measured by the CSS (median = 24; Q1-Q3 =
11-75; n = 85). Five of the patients recovered from cold hypersensitivity, and ~
40% of the patients were less affected by cold hypersensitivity in daily life.
Little or no pain early after injury and higher CSS-scores 12 months after
primary surgery were weakly associated with the reduced CSS-scores (R(2) = 0.20)
at the 3-year follow-up. Six patients had changed work or did not work due to
cold hypersensitivity, but the majority of the patients had kept their cold
exposed work. CONCLUSION: Cold-hypersensitive patients may have a reasonable
chance for decreased cold sensitivity and cold-associated activity limitations
over time, although the majority of the patients will experience persistent
problems. Tools to predict improvement remain insufficient.
PMID- 26413979
TI - Development and Pilot Testing of an Encounter Tool for Shared Decision Making
About the Treatment of Graves' Disease.
AB - BACKGROUND: The best treatment option for patients with Graves' disease (GD)
depends on each person's situation and how the differences between the treatment
options matter to them in bringing resolution to their illness. The objective of
this study was to develop and test an encounter decision tool (GD Choice) for
patients and clinicians to engage in shared decision making about the treatment
of GD. METHODS: GD Choice was developed using an iterative process based on the
principles of interaction design and participatory action research. To evaluate
the impact of the tool, a controlled before-after study was conducted, assessing
the use of GD Choice versus usual care (UC). RESULTS: Sixty-eight patients were
enrolled, 37 to UC and 31 to GD Choice. At baseline, the groups were similar.
Treatment discussion length was similar in both arms. After their visit, patients
in both groups had similar knowledge about the options, except for GD Choice
patients knowing significantly more about the complications of treatment
(correctly answered by 83% vs. 55%; p = 0.04). Compared with UC, patients in the
GD Choice arm had greater involvement in decision making observed on video
recordings of clinical encounters (mean OPTION scale score, 35% vs. 30%; p =
0.02), but reported similar levels of decisional comfort and participation in
shared decision making. CONCLUSIONS: GD Choice increases engagement in the
decision-making process and knowledge regarding intervention complications
without increasing the length of consultation. These promising results support
the conduct of a randomized trial of GD Choice versus UC in a large multicenter
trial.
PMID- 26413978
TI - Genetics of pancreatic neuroendocrine tumors: implications for the clinic.
AB - Pancreatic neuroendocrine tumors (PanNETs) are a common and deadly neoplasm of
the pancreas. Although the importance of genetic alterations in PanNETs has been
known for many years, recent comprehensive sequencing studies have greatly
expanded our knowledge of neuroendocrine tumorigenesis in the pancreas. These
studies have identified specific cellular processes that are altered in PanNETs,
highlighted alterations with prognostic implications, and pointed to pathways for
targeted therapies. In this review, we will discuss the genetic alterations that
play a key role in PanNET tumorigenesis, with a specific focus on those
alterations with the potential to change the way patients with these neoplasms
are diagnosed and treated.
PMID- 26413981
TI - Re-examination of genetic and nutritional factors related to trichothecene
biosynthesis in Fusarium graminearum.
AB - Disruption of two Fusarium genes that negatively regulate trichothecene
biosynthesis was reported to cause a drastic increase in trichothecene
production. However, careful inspection of these genes revealed that neither was
significantly related to trichothecene production. Agmatine medium maintained the
expression of trichothecene genes at significant levels, resulting in a 2-3-fold
increase in the final yield, as compared to glutamine medium.
PMID- 26413983
TI - The effect of the pre-pregnancy weight of the mother and the gestational weight
gain on the bilirubin level of term newborn.
AB - OBJECTIVE: Jaundice is a problem in newborns. There are many maternal and infant
related factors affecting neonatal jaundice. The maternal pre-pregnancy weight,
maternal body mass index (BMI) and gestational weight gain may have an effect on
the newborn bilirubin levels. We research the effect of the maternal pre
pregnancy weight and gestational weight gain on the bilirubin levels of the
newborn infants in the first 2 weeks prospectively. METHODS: Term and healthy
infants who were born between 38 and 42 weeks in our clinic were included in the
study. Maternal pre-pregnancy BMIs were calculated. Babies were divided into
three groups according to their mothers' advised amount of gestational weight
gain. Total serum bilirubin (TSB) values of the newborns were measured in the
2nd, 5th and 15th postnatal days. RESULTS: In our study, the 5th and 15th day
capillary bilirubin level of the babies with mothers who gained more weight than
the advised amount during pregnancy were found statistically significant higher
compared to the other two groups (p < 0.05). Similarly, the hematocrit level of
the babies with mothers who gained more weight than the advised amount were found
statistically significant higher compared to the other two groups (p < 0.05).
CONCLUSIONS: We conclude that the babies with mothers who gained more weight than
the advised amount were under risk for newborn jaundice. Therefore, these babies
should be monitored more closely for neonatal jaundice and prolonged jaundice.
PMID- 26413982
TI - A phase II study of oxaliplatin and prednisone for patients with relapsed or
refractory marginal zone lymphoma: Consortium for Improving Survival of Lymphoma
trial.
AB - Overall, more than 50% of marginal zone lymphoma (MZL) patients experience a
relapse within 10 years. This phase II trial was conducted to assess the efficacy
and safety of oxaliplatin-prednisone (Ox-P) chemotherapy for patients with
relapsed or refractory MZL. Patients received oxaliplatin 130 mg/m(2) on day 1
and prednisone 100 mg/day on days 1-5 of each cycle. A total of 38 patients were
enrolled. The median age of the 34 (16 males, 18 females) evaluated patients was
53 (range = 27-74) years. There were seven complete responses (20.6%) and 15
partial responses (44.1%) (Overall response rate = 64.7%). No treatment-related
deaths occurred. The median progression-free survival was 14.2 months (95% CI =
2.1-26.3 months); 3-year overall survival rate was 77.7%. Thus, salvage Ox-P
chemotherapy for patients with relapsed or refractory MZL at the stated dosage
and schedule showed moderate clinical activity and was considerable in very few
selected patients (NCT01068392).
PMID- 26413984
TI - Architectured materials: Straining to expand entanglements.
PMID- 26413985
TI - A sunblock based on bioadhesive nanoparticles.
AB - The majority of commercial sunblock preparations use organic or inorganic
ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity,
direct cellular exposure to UV filters has raised a variety of health concerns.
Here, we show that the encapsulation of padimate O (PO)--a model UV filter--in
bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV
filters while enhancing UV protection. BNPs are readily suspended in water,
facilitate adherence to the stratum corneum without subsequent intra-epidermal or
follicular penetration, and their interaction with skin is water resistant yet
the particles can be removed via active towel drying. Although the sunblock based
on BNPs contained less than 5 wt% of the UV-filter concentration found in
commercial standards, the anti-UV effect was comparable when tested in two murine
models. Moreover, the BNP-based sunblock significantly reduced double-stranded
DNA breaks when compared with a commercial sunscreen formulation.
PMID- 26413986
TI - Nanoscale transport of charge-transfer states in organic donor-acceptor blends.
AB - Charge-transfer (CT) states, bound combinations of an electron and a hole on
separate molecules, play a crucial role in organic optoelectronic devices. We
report direct nanoscale imaging of the transport of long-lived CT states in
molecular organic donor-acceptor blends, which demonstrates that the bound
electron-hole pairs that form the CT states move geminately over distances of 5
10 nm, driven by energetic disorder and diffusion to lower energy sites. Magnetic
field dependence reveals a fluctuating exchange splitting, indicative of a
variation in electron-hole spacing during diffusion. The results suggest that the
electron-hole pair of the CT state undergoes a stretching transport mechanism
analogous to an 'inchworm' motion, in contrast to conventional transport of
Frenkel excitons. Given the short exciton lifetimes characteristic of bulk
heterojunction organic solar cells, this work confirms the potential importance
of CT state transport, suggesting that CT states are likely to diffuse farther
than Frenkel excitons in many donor-acceptor blends.
PMID- 26413987
TI - Plasmons in graphene moire superlattices.
AB - Moire patterns are periodic superlattice structures that appear when two crystals
with a minor lattice mismatch are superimposed. A prominent recent example is
that of monolayer graphene placed on a crystal of hexagonal boron nitride. As a
result of the moire pattern superlattice created by this stacking, the electronic
band structure of graphene is radically altered, acquiring satellite sub-Dirac
cones at the superlattice zone boundaries. To probe the dynamical response of the
moire graphene, we use infrared (IR) nano-imaging to explore propagation of
surface plasmons, collective oscillations of electrons coupled to IR light. We
show that interband transitions associated with the superlattice mini-bands in
concert with free electrons in the Dirac bands produce two additive contributions
to composite IR plasmons in graphene moire superstructures. This novel form of
collective modes is likely to be generic to other forms of moire-forming
superlattices, including van der Waals heterostructures.
PMID- 26413989
TI - Prenatal serum screening markers may not require adjustment in former smokers.
PMID- 26413988
TI - Reversible dilatancy in entangled single-wire materials.
AB - Designing structures that dilate rapidly in both tension and compression would
benefit devices such as smart filters, actuators or fasteners. This property
however requires an unusual Poisson ratio, or Poisson function at finite strains,
which has to vary with applied strain and exceed the familiar bounds: less than 0
in tension and above 1/2 in compression. Here, by combining mechanical tests and
discrete element simulations, we show that a simple three-dimensional architected
material, made of a self-entangled single long coiled wire, behaves in between
discrete and continuum media, with a large and reversible dilatancy in both
tension and compression. This unusual behaviour arises from an interplay between
the elongation of the coiled wire and rearrangements due to steric effects,
which, unlike in traditional discrete media, are hysteretically reversible when
the architecture is made of an elastic fibre.
PMID- 26413991
TI - Hypercoagulability in Kidney Transplant Recipients.
AB - Thrombosis remains an important complication after kidney transplantation.
Outcomes for graft and deep vein thrombosis are not favorable. The majority of
early kidney transplant failure in adults is due to allograft thrombosis. Risk
stratification, early diagnosis, and appropriate intervention are critical to the
management of thrombotic complications of transplant. In patients with end-stage
renal disease, the prevalence of acquired risk factors for thrombosis is
significantly high. Because of hereditary and acquired risk factors, renal
transplant recipients manifest features of a chronic prothrombotic state.
Identification of hereditary thrombotic risk factors before transplantation may
be a useful tool for selecting appropriate candidates for thrombosis prophylaxis
immediately after transplantation. Short-term anticoagulation may be appropriate
for all patients after kidney transplantation.
PMID- 26413992
TI - Glucose Effectiveness: The Mouse Trap in the Development of Novel beta-Cell
Replacement Therapies.
AB - BACKGROUND: Cure of diabetes and normalization of glucose disposal during
intravenous glucose tolerance tests (IVGTT) remains critical for stringent
evaluation of novel replacement therapies in type 1 diabetes. Glucose disposal
during an IVGTT depends on a complex interaction of both insulin-dependent and
independent mechanisms. Glucose effectiveness, that is, the function of glucose
per se, independent of insulin, to stimulate its uptake and suppress endogenous
glucose production is less recognized. METHODS: To unravel the relative
importance of these pathways, rats were injected with streptozotocin to induce
diabetes and implanted subcutaneously with slow-release devices of insulin.
RESULTS: These animals demonstrated rapid normalization of blood glucose and
perfectly normal glucose disposal during an IVGTT with no differences when
compared with nondiabetic controls even though no active c-peptide secretion was
detected in plasma and almost no remaining insulin-producing cells were present
in the pancreas. CONCLUSIONS: The present study highlights that glucose is the
predominant mediator of its own disposal in rodents having only basal and
nonglucose-regulated plasma insulin levels. The herein presented results calls
for a reassessment how results obtained in the most commonly used experimental
models should be interpreted in the development of future replacement therapies
in type 1 diabetes.
PMID- 26413993
TI - Peritubular Capillary Basement Membrane Multilayering in Renal Allograft Biopsies
of Patients With De Novo Donor-Specific Antibodies.
AB - BACKGROUND: Severe peritubular capillary basement membrane multilayering (PTCBML)
is part of the Banff definition of chronic antibody-mediated rejection. We
retrospectively investigated whether assessment of the mean number of layers of
basement membrane (BM) around peritubular capillaries (PTC) can be used in a
cohort of patients with de novo donor-specific antibodies (dnDSA) as an early
marker to predict long-term antibody-mediated injury. METHODS: This is a
retrospective cohort study with 151 electron microscopy samples from 54 patients
with dnDSA, assessed at around 1 year after transplantation, for a mean number of
BM layers around PTC and in serial biopsies. Graft survival and time to
transplant glomerulopathy (TG) development were estimated in survival analyses.
RESULTS: We found that a mean PTCBML count greater than 2.5 layers assessed in a
sample of 25 PTCs around 1 year after transplantation is indicative of the
development of TG in patients with dnDSA (P = 0.001). In addition, in patients
with serial biopsies available for electron microscopy analysis, we could
distinguish 2 groups: patients with a mean PTCBML count of 2.5 or less on all
biopsies, and patients who developed greater than 2.5 layers at any time after
transplantation. The latter group reflected dnDSA patients at risk for TG
development (P < 0.001). In patients with dnDSA, PTCBML score added significantly
to the sensitivity and specificity of prediction of TG compared with
microcirculation injury score alone. CONCLUSIONS: Our results highlight the
potential value of assessing the mean number of BM in PTC for early prediction of
progression to chronic antibody-mediated injury.
PMID- 26413990
TI - Impact of Tacrolimus Compared With Cyclosporin on the Incidence of Acute
Allograft Rejection in Human Immunodeficiency Virus-Positive Kidney Transplant
Recipients.
AB - BACKGROUND: Kidney transplantation (KT) of human immunodeficiency virus (HIV)
positive patients has transformed the management of end-stage kidney disease in
this population. Although favourable outcomes have been reported, patients
experience high rates of acute allograft rejection (AR). We examined factors
associated with AR in the first year after KT, with particular emphasis on the
choice of calcineurin inhibitor (CNI) immunosuppressive therapy. METHODS: We
conducted a national observational cohort study of HIV/KT in the United Kingdom.
Patients were included if HIV positive at KT, transplanted in the United Kingdom
between January 2005 and December 2013, and did not experience primary graft
failure. Kaplan-Meier methods were used to estimate host/graft survival and
cumulative incidence of biopsy proven AR. Logrank tests were used to compare
survival, and Cox proportional hazard models to examine factors associated with
AR. RESULTS: Our study analyzed the incidence of AR in the first year after KT in
78 HIV-positive patients of whom 31 initiated cyclosporin (CsA) and 47 tacrolimus
(Tac) based immunosuppression. AR was observed in 28 patients (36%) after a
median of 2.6 (interquartile range, 0.5-5.9) months. The cumulative incidence of
AR at 1 year was 58% and 21% among patients on CsA and Tac, respectively (P
=0.003). Choice of CNI was the only factor significantly associated with AR
(hazard ratio for Tac vs CsA 0.25 [95% confidence interval, 0.11-0.57], P =
0.001). Subtherapeutic CNI concentrations were common in the first 12 weeks after
KT. CONCLUSIONS: Our data suggest that Tac may be the preferred CNI for use in KT
in people living with HIV.
PMID- 26413994
TI - Engaging in Culturally Informed Nursing Care With Hmong Children and Their
Families.
AB - The Hmong are an ethnic hill tribe group originally from Southern China with
concentrated populations throughout Southeast Asia, especially the mountains of
northern Laos. Following the Vietnam War, the Hmong started immigrating to the
United States in waves to escape prosecution for fighting communism alongside the
United States. Today, the Hmong population in the United States is growing
rapidly, with a median age of 20.4 years. As the Hmong move and redistribute
themselves across the country to be with family or pursue new opportunities, it
is more and more likely that nurses everywhere will interact with Hmong children
and their families. Historically medically underserved, the Hmong community
continues to face barriers to healthcare as a result of culture, language, and
lack of access. Nurses who are informed about cultural values and norms of the
Hmong and their family and social structures, as well as their spiritual and
traditional practices, will be able to establish trust with their pediatric
patients and their caregivers. Utilizing strategies including interpretive
services, asking detailed social and physical histories, providing extra
appointment time, asking open ended questions, and employing teach back methods
can help improve communication as well as provide higher quality care that
addresses the specific needs of this population.
PMID- 26413995
TI - MET/HGF targeted drugs as potential therapeutic strategies in non-small cell lung
cancer.
PMID- 26413997
TI - Rotational Orientation Effects in NO(X) + Ar Inelastic Collisions.
AB - Rotational angular momentum orientation effects in the rotationally inelastic
collisions of NO(X) with Ar have been investigated both experimentally and
theoretically at a collision energy of 530 cm(-1). The collision-induced
orientation has been determined experimentally using a hexapole electric field to
select the epsilon = -1 Lambda-doublet level of the NO(X) j = 1/2 initial state.
Fully quantum state resolved polarization-dependent differential cross sections
were recorded experimentally using a crossed molecular beam apparatus coupled
with a (1 + 1') resonance-enhanced multiphoton ionization detection scheme and
subsequent velocity-map imaging. To determine the NO sense of rotation, the probe
radiation was circularly polarized. Experimental orientation polarization
dependent differential cross sections are compared with those obtained from
quantum mechanical scattering calculations and are found to be in good agreement.
The origin of the collision-induced orientation has been investigated by means of
close-coupled quantum mechanical, quantum mechanical hard shell, quasi-classical
trajectory (QCT), and classical hard shell calculations at the same collision
energy. Although there is evidence for the operation of limiting classical
mechanisms, the rotational orientation cannot be accounted for by QCT
calculations and is found to be strongly influenced by quantum mechanical
effects.
PMID- 26413996
TI - Challenges and Prospects for Alpha-1 Antitrypsin Deficiency Gene Therapy.
AB - Alpha-1 antitrypsin (AAT) is a protease inhibitor belonging to the serpin family.
A number of identified mutations in the SERPINA1 gene encoding this protein
result in alpha-1 antitrypsin deficiency (AATD). A decrease in AAT serum
concentration or reduced biological activity causes considerable risk of chronic
respiratory and liver disorders. As a monogenic disease, AATD appears to be an
attractive target for gene therapy, particularly for patients with pulmonary
dysfunction, where augmentation of functional AAT levels in plasma might slow
down respiratory disease development. The short AAT coding sequence and its
activity in the extracellular matrix would enable an increase in systemic serum
AAT production by cellular secretion. In vitro and in vivo experimental AAT gene
transfer with gamma-retroviral, lentiviral, adenoviral, and adeno-associated
viral (AAV) vectors has resulted in enhanced AAT serum levels and a promising
safety profile. Human clinical trials using intramuscular viral transfer with
AAV1 and AAV2 vectors of the AAT gene demonstrated its safety, but did not
achieve a protective level of AAT >11 MUM in serum. This review provides an in
depth critical analysis of current progress in AATD gene therapy based on viral
gene transfer. The factors affecting transgene expression levels, such as site of
administration, dose and type of vector, and activity of the immune system, are
discussed further as crucial variables for optimizing the clinical effectiveness
of gene therapy in AATD subjects.
PMID- 26413999
TI - Genetically Programmed Clusters of Gold Nanoparticles for Cancer Cell-Targeted
Photothermal Therapy.
AB - Interpretations of the interactions of nanocarriers with biological cells are
often complicated by complex synthesis of materials, broad size distribution, and
heterogeneous surface chemistry. Herein, the major capsid proteins of an
icosahedral T7 phage (55 nm in diameter) are genetically engineered to display a
gold-binding peptide and a prostate cancer cell-binding peptide in a tandem
sequence. The genetically modified phage attracts gold nanoparticles (AuNPs) to
form a cluster of gold nanoparticles (about 70 nanoparticles per phage). The
cluster of AuNPs maintains cell-targeting functionality and exhibits excellent
dispersion stability in serum. Under a very low light irradiation (60 mW cm(-2)),
only targeted AuNP clusters kill the prostate cancer cells in minutes (not in
other cell types), whereas neither nontargeted AuNP clusters nor citrate
stabilized AuNPs cause any significant cell death. The result suggests that the
prostate cancer cell-targeted clusters of AuNPs are targeted to only prostate
cancer cells and, when illuminated, generate local heating to more efficiently
and selectively kill the targeted cancer cells. Our strategy can be generalized
to target other types of cells and assemble other kinds of nanoparticles for a
broad range of applications.
PMID- 26413998
TI - Surfactant Effects on Particle Generation in Antibody Formulations in Pre-filled
Syringes.
AB - Protein aggregation and particle formation have been observed when protein
solutions contact hydrophobic interfaces, and it has been suggested that this
undesirable phenomenon may be initiated by interfacial adsorption and subsequent
gelation of the protein. The addition of surfactants, such as polysorbate 20, to
protein formulations has been proposed as a way to reduce protein adsorption at
silicone oil-water interfaces and mitigate the production of aggregates and
particles. In an accelerated stability study, monoclonal antibody formulations
containing varying concentrations of polysorbate 20 were incubated and agitated
in pre-filled glass syringes (PFS), exposing the protein to silicone oil-water
interfaces at the siliconized syringe walls, air-water interfaces, and agitation
stress. Following agitation in siliconized syringes that contained an air bubble,
lower particle concentrations were measured in the surfactant-containing antibody
formulations than in surfactant-free formulations. Polysorbate 20 reduced
particle formation when added at concentrations above or below the critical
micelle concentration (CMC). The ability of polysorbate 20 to decrease particle
generation in PFS corresponded with its ability to inhibit gelation of the
adsorbed protein layer, which was assessed by measuring the interfacial diffusion
of individual antibody molecules at the silicone oil-water interface using total
internal reflectance fluorescence (TIRF) microscopy with single-molecule
tracking.
PMID- 26414000
TI - Confinement of Surface Plasmon Polaritons by Heterostructures of Plasmonic
Crystals.
AB - Square lattice plasmonic crystals (SQ-PlCs) composed of silver pillars generate
large bandgaps for surface plasmon polaritons (SPPs). SPP confinement is
demonstrated using one- and two-dimensional heterostructures of SQ-PlCs comprised
of cylindrical pillars with different diameters in a common square lattice. Two
kinds of localized modes are observed to appear in the heterostructures by photon
map imaging using cathodoluminescence (CL) technique combined with a scanning
transmission electron microscopy (STEM). Angle-resolved CL spectroscopy reveals
contrasting characteristics of the two localized modes in their emission
distributions, indicating that they originate from the band-edge A and E modes of
the matrix SQ-PlC.
PMID- 26414001
TI - Nonosseous Tarsal Coalition of the Lateral Cuneocuboid Joint: A Case Report.
AB - We describe a rare case of a nonosseous coalition of the lateral cuneocuboid
joint with peroneal spasm that we successfully treated with resection. A 60-year
old female had been experiencing constant pain in her right foot, particularly
when walking and going up and down stairs. The pain had been present for
approximately 1 year after she had experienced a minor injury. Her right ankle
showed plantar flexion restrictions (right 20 degrees and left 40 degrees ) and
was held in an antalgic valgus position. Sudden passive plantar flexion produced
pain behind the lateral malleolus of the right ankle. Tenderness was detected in
the right peroneus brevis tendon and the right sinus tarsi. On plain radiographs,
the oblique view showed an irregularity in the articular surface of the lateral
cuneocuboid joint in both feet. On computed tomography images, there was no
osseous continuation in the lateral cuneocuboid joint, indicative of a nonosseous
bridge between the lateral cuneiform and the cuboid. The nonosseous coalition
between the lateral cuneiform and the cuboid was resected and the trabecular
surfaces and cortical margins covered with a thin film of bone wax. The patient's
recovery was unremarkable, and 1 year after surgery, she was able to walk without
pain and was able to perform her usual activities and job.
PMID- 26414002
TI - The role of mothers' and fathers' religiosity in African American adolescents'
religious beliefs and practices.
AB - OBJECTIVES: To advance understanding of youth religiosity in its sociocultural
context, this study examined the associations between parents' and adolescents'
religious beliefs and practices and tested the roles of parent and youth gender
and youth ethnic identity in these linkages. METHOD: The sample included 130 two
parent, African American families. Adolescents (49% female) averaged 14.43 years
old. Mothers, fathers, and adolescents were interviewed in their homes about
their family and personal characteristics, including their religious beliefs. In
a series of 7 nightly phone calls, adolescents reported on their daily practices,
including time spent in religious practices (e.g., attending services, prayer),
and parents reported on their time spent in religious practices with their
adolescents. RESULTS: Findings indicated that mothers' beliefs were linked to the
beliefs of sons and daughters, but fathers' beliefs were only associated with the
beliefs of sons. Mothers' practices were associated with youths' practices, but
the link was stronger when mothers' held moderately strong religious beliefs.
Fathers' practices were also linked to youth practices, but the association was
stronger for daughters than for sons. CONCLUSIONS: Findings highlight the
understudied role of fathers in African American families, the importance of
examining religiosity as a multidimensional construct, and the utility of ethnic
homogeneous designs for illuminating the implications of sociocultural factors in
the development of African American youth. (PsycINFO Database Record
PMID- 26414005
TI - Children's Interstitial and Diffuse Lung Disease. Progress and Future Horizons.
AB - Children's interstitial and diffuse lung disease (chILD) is a term that
encompasses a large and diverse group of rare pediatric diseases and disorders.
Significant progress has been made over the last 2 decades in classification,
clinical care, research, and organizational structure to enhance the care of
children with these high-morbidity and -mortality diseases. New diseases have
been defined clinically and genetically, classification systems developed and
applied, organizations formed such as the chILD Research Network (chILDRN) and
chILD Foundation, and basic and translational science expanded to focus on chILD
diseases. Multidisciplinary collaborations and efforts to advance understanding
and treatment of chILD have been extended worldwide. The future horizon holds
great promise to expand scientific discoveries, collaborate more broadly, and
bring new treatment to these children. An overview of key historical past
developments, major clinical and research updates, and opportunities for the
future in chILD is reviewed in this Perspective.
PMID- 26414004
TI - Course of Magnetic Resonance Imaging-Detected Inflammation and Structural Lesions
in the Sacroiliac Joints of Patients in the Randomized, Double-Blind, Placebo
Controlled Danish Multicenter Study of Adalimumab in Spondyloarthritis, as
Assessed by the Berlin and Spondyloarthritis Research Consortium of Canada
Methods.
AB - OBJECTIVE: To investigate changes in magnetic resonance imaging (MRI)-assessed
inflammation and structural lesions in the sacroiliac (SI) joints during
treatment with adalimumab versus placebo. METHODS: In a 48-week double-blind,
placebo-controlled trial, 52 patients with spondyloarthritis were randomized to
receive subcutaneous injections of either adalimumab 40 mg (n = 25) or placebo (n
= 27) every other week for 12 weeks. Patients in the adalimumab group continued
to receive and patients in the placebo group were switched to adalimumab 40 mg
every other week for an additional 12 weeks. MRI of the SI joints was performed
at weeks 0, 12, 24, and 48, and the images were assessed independently in a
blinded manner using the modified Berlin and the Spondyloarthritis Research
Consortium of Canada (SPARCC) MRI scores for inflammation and structural lesions
of the SI joints. RESULTS: At baseline, 56% of the adalimumab group and ~72% of
the placebo group had an MRI-assessed inflammation score of >=1. Among the
patients with inflammation at baseline, the mean percent reductions in MRI scores
for inflammation from week 0 to 12 were greater in the adalimumab group compared
with the placebo group (Berlin method, -62% versus -5%; SPARCC method, -58%
versus -12% [both P < 0.04]). Furthermore, the mean SPARCC erosion score
decreased (-0.6) and the SPARCC backfill score increased (+0.8) in the adalimumab
group from week 0 to week 12. From week 12 to week 24, larger absolute reductions
in the Berlin/SPARCC inflammation scores and the SPARCC erosion score and larger
increases in the Berlin/SPARCC fatty lesion scores were seen in the placebo group
compared with the adalimumab group. In univariate regression analyses (analysis
of covariance) and multivariate stepwise regression analyses, treatment with
adalimumab was independently associated with regression of the SPARCC erosion
score from week 0 to 12 but not with changes in the other types of MRI lesions.
CONCLUSION: Significant changes in the Berlin and SPARCC MRI-assessed
inflammation scores and in the SPARCC MRI-assessed erosion scores occurred within
12 weeks after initiation of adalimumab. Tumor necrosis factor inhibitor
treatment was associated with resolution of erosions and the development of
backfill.
PMID- 26414003
TI - Increased sphingosine 1-phosphate mediates inflammation and fibrosis in tubular
injury in diabetic nephropathy.
AB - Hyperglycemia induces all isoforms of transforming growth factor beta (TGFbeta),
which in turn play key roles in inflammation and fibrosis that characterize
diabetic nephropathy. Sphingosine 1-phosphate (S1P) is a signaling sphingolipid,
derived from sphingosine by the action of sphingosine kinase (SK). S1P mediates
many biological processes, which mimic TGFbeta signaling. To determine the role
of SK1 and S1P in inducing fibrosis and inflammation, and the interaction with
TGFbeta-1, 2 and 3 signalling in diabetic nephropathy, human proximal tubular
cells (HK2 cells) were exposed to normal (5 mmol/L) or high (30 mmol/L) glucose
or TGFbeta-1, -2, -3 +/- an SK inhibitor (SKI-II) or SK1 siRNA. Control and
diabetic wild type (WT) and SK1(-/-) mice were studied. Fibrotic and inflammatory
markers, and relevant downstream signalling pathways were assessed. SK1 mRNA and
protein expression was increased in HK2 cells exposed to high glucose or
TGFbeta1,-2,-3. All TGFbeta isoforms induced fibronectin, collagen IV and
macrophage chemoattractant protein 1 (MCP1), which were reversed by both SKI-II
and SK1 siRNA. Exposure to S1P increased phospho-p44/42 expression, AP-1 binding
and NFkB phosphorylation. WT diabetic mice exhibited increased renal cortical
S1P, fibronectin, collagen IV and MCP1 mRNA and protein expression compared to
SK1(-/-) diabetic mice. In summary, this study demonstrates that inhibiting the
formation of S1P reduces tubulointerstitial renal inflammation and fibrosis in
diabetic nephropathy.
PMID- 26414006
TI - The Effects of Thermal Radiation on an Unsteady MHD Axisymmetric Stagnation-Point
Flow over a Shrinking Sheet in Presence of Temperature Dependent Thermal
Conductivity with Navier Slip.
AB - In this paper, the magnetohydrodynamic (MHD) axisymmetric stagnation-point flow
of an unsteady and electrically conducting incompressible viscous fluid in with
temperature dependent thermal conductivity, thermal radiation and Navier slip is
investigated. The flow is due to a shrinking surface that is shrunk
axisymmetrically in its own plane with a linear velocity. The magnetic field is
imposed normally to the sheet. The model equations that describe this fluid flow
are solved by using the spectral relaxation method. Here, heat transfer processes
are discussed for two different types of wall heating; (a) a prescribed surface
temperature and (b) a prescribed surface heat flux. We discuss and evaluate how
the various parameters affect the fluid flow, heat transfer and the temperature
field with the aid of different graphical presentations and tabulated results.
PMID- 26414007
TI - Evidence-Based Guideline of the German Nutrition Society: Fat Intake and
Prevention of Selected Nutrition-Related Diseases.
AB - As nutrition-related chronic diseases have become more and more frequent, the
importance of dietary prevention has also increased. Dietary fat plays a major
role in human nutrition, and modification of fat and/or fatty acid intake could
have a preventive potential. The aim of the guideline of the German Nutrition
Society (DGE) was to systematically evaluate the evidence for the prevention of
the widespread diseases obesity, type 2 diabetes mellitus, dyslipoproteinaemia,
hypertension, metabolic syndrome, coronary heart disease (CHD), stroke, and
cancer through the intake of fat or fatty acids. The main results can be
summarized as follows: it was concluded with convincing evidence that a reduced
intake of total and saturated fat as well as a larger intake of polyunsaturated
fatty acids (PUFA) at the expense of saturated fatty acids (SFA) reduces the
concentration of total and low-density lipoprotein cholesterol in plasma.
Furthermore, there is convincing evidence that a high intake of trans fatty acids
increases risk of dyslipoproteinaemia and that a high intake of long-chain
polyunsaturated n-3 fatty acids reduces the triglyceride concentration in plasma.
A high fat intake increases the risk of obesity with probable evidence when total
energy intake is not controlled for (ad libitum diet). When energy intake is
controlled for, there is probable evidence for no association between fat intake
and risk of obesity. A larger intake of PUFA at the expense of SFA reduces risk
of CHD with probable evidence. Furthermore, there is probable evidence that a
high intake of long-chain polyunsaturated n-3 fatty acids reduces risk of
hypertension and CHD. With probable evidence, a high trans fatty acid intake
increases risk of CHD. The practical consequences for current dietary
recommendations are described at the end of this article.
PMID- 26414008
TI - Choosing Wisely in Daily Practice: An Intervention Study on Antinuclear Antibody
Testing by Rheumatologists.
AB - OBJECTIVE: To assess the effect of a simple intervention on antinuclear antibody
(ANA) test overuse by rheumatologists. METHODS: This was an explorative,
pragmatic, before-and-after, controlled implementation study among
rheumatologists working at 3 rheumatology departments in secondary and tertiary
care centers in The Netherlands. The intervention was given in all study centers
separately and combined education with feedback. Six outcome measures describe
the intervention effects: the ANA/new patient ratio (APR), difference with the
target APR, percentage of positive ANA tests, percentage of repeated ANA testing,
percentage of ANA-associated diseases, and APR variation between rheumatologists.
Outcomes were compared between the pre- and postintervention period (both 12
months) using (multilevel) logistic regression or F testing. Results are reported
together for centers 1 and 2, and separately for center 3, because ANA tests
could not be linked to an individual rheumatologist in center 3. RESULTS: The APR
decreased from 0.37 to 0.11 after the intervention in centers 1 and 2 (odds ratio
[OR] 0.19, 95% confidence interval [95% CI] 0.17-0.22, P < 0.001) and from 0.45
to 0.30 in center 3 (OR 0.53, 95% CI 0.45-0.62, P < 0.001). The percentage of
repeated ANA requests in all centers and the APR variation for centers 1 and 2
decreased significantly. Only in center 3 did the percentage of ANA-associated
diseases increase significantly. CONCLUSION: A simple intervention resulted in a
relevant and significant decrease in the numbers of ANA tests requested by
rheumatologists, together with an improvement on 3 other outcome measures.
PMID- 26414009
TI - Elucidation of Enzymatic Mechanism of Phenazine Biosynthetic Protein PhzF Using
QM/MM and MD Simulations.
AB - The phenazine biosynthetic pathway is of considerable importance for the
pharmaceutical industry. The pathway produces two products: phenazine-1,6
dicarboxylic acid and phenazine-1-carboxylic acid. PhzF is an isomerase that
catalyzes trans-2,3-dihydro-3-hydroxyanthranilic acid isomerization and plays an
essential role in the phenazine biosynthetic pathway. Although the PhzF crystal
structure has been determined recently, an understanding of the detailed
catalytic mechanism and the roles of key catalytic residues are still lacking. In
this study, a computational strategy using a combination of molecular modeling,
molecular dynamics simulations, and quantum mechanics/molecular mechanics
simulations was used to elucidate these important issues. The Apo enzyme, enzyme
substrate complexes with negatively charged Glu45, enzyme-transition state analog
inhibitor complexes with neutral Glu45, and enzyme-product complexes with
negatively charged Glu45 structures were optimized and modeled using a 200 ns
molecular dynamics simulation. Residues such as Gly73, His74, Asp208, Gly212,
Ser213, and water, which play important roles in ligand binding and the
isomerization reaction, were comprehensively investigated. Our results suggest
that the Glu45 residue at the active site of PhzF acts as a general base/acid
catalyst during proton transfer. This study provides new insights into the
detailed catalytic mechanism of PhzF and the results have important implications
for PhzF modification.
PMID- 26414010
TI - Amelioration of nicotinamide adenine dinucleotide phosphate-oxidase mediated
stress reduces cell death after blast-induced traumatic brain injury.
AB - A total of 1.7 million traumatic brain injuries (TBIs) occur each year in the
United States, but available pharmacologic options for the treatment of acute
neurotrauma are limited. Oxidative stress is an important secondary mechanism of
injury that can lead to neuronal apoptosis and subsequent behavioral changes.
Using a clinically relevant and validated rodent blast model, we investigated how
nicotinamide adenine dinucleotide phosphate oxidase (Nox) expression and
associated oxidative stress contribute to cellular apoptosis after single and
repeat blast injuries. Nox4 forms a complex with p22phox after injury, forming
free radicals at neuronal membranes. Using immunohistochemical-staining methods,
we found a visible increase in Nox4 after single blast injury in Sprague Dawley
rats. Interestingly, Nox4 was also increased in postmortem human samples obtained
from athletes diagnosed with chronic traumatic encephalopathy. Nox4 activity
correlated with an increase in superoxide formation. Alpha-lipoic acid, an
oxidative stress inhibitor, prevented the development of superoxide acutely and
increased antiapoptotic markers B-cell lymphoma 2 (t = 3.079, P < 0.05) and heme
oxygenase 1 (t = 8.169, P < 0.001) after single blast. Subacutely, alpha-lipoic
acid treatment reduced proapoptotic markers Bax (t = 4.483, P < 0.05), caspase 12
(t = 6.157, P < 0.001), and caspase 3 (t = 4.573, P < 0.01) after repetitive
blast, and reduced tau hyperphosphorylation indicated by decreased CP-13 and
paired helical filament staining. Alpha-lipoic acid ameliorated impulsive-like
behavior 7 days after repetitive blast injury (t = 3.573, P < 0.05) compared with
blast exposed animals without treatment. TBI can cause debilitating symptoms and
psychiatric disorders. Oxidative stress is an ideal target for neuropharmacologic
intervention, and alpha-lipoic acid warrants further investigation as a
therapeutic for prevention of chronic neurodegeneration.
PMID- 26414011
TI - Microvesicles but Not Exosomes from Pathfinder Cells Stimulate Functional
Recovery of the Pancreas in a Mouse Streptozotocin-Induced Diabetes Model.
AB - Pathfinder cells (PCs), a novel cell type derived from the pancreas of adult
rats, have been demonstrated to stimulate recovery of tissue structure and
function in two animal models of acute tissue damage to date-streptozotocin (STZ)
induced diabetes and ischemia-reperfusion damage to the kidney. In repaired
tissue, PCs and their progeny typically represent only 0.02% of the repaired
tissue, suggesting that they act via a paracrine mechanism on native cells in the
damaged area. Extracellular vesicles are strong candidates for mediating such a
paracrine effect. Therefore, we studied the effects of two PC-derived
extracellular vesicle fractions on tissue repair in the STZ diabetes model, one
containing primarily microvesicles and the second containing predominantly
exosomes. Treatment of STZ-induced diabetic mice with the microvesicles
preparation led to blood glucose, insulin, glucagon, and C-peptide levels similar
to those found with PC treatment. Furthermore, analysis of the histopathology of
the pancreas indicated islet regeneration. In contrast, the exosome fraction
demonstrated no repair activity, and STZ diabetic mice treated with exosome
preparations had blood glucose values that were indistinguishable from those of
vehicle-only treated controls. Therefore, we conclude that exosomes play no part
in PC action as detected by this assay, whereas microvesicles provide all or a
large component of the paracrine activity of PCs. Because they act to stimulate
repair of multiple tissues, PC-derived microvesicles may similarly have the
potential to stimulate repair of many damaged tissues, identifying a very
significant cell-free therapeutic opportunity in regenerative medicine.
PMID- 26414012
TI - Isolated Primary Blast Inhibits Long-Term Potentiation in Organotypic Hippocampal
Slice Cultures.
AB - Over the last 13 years, traumatic brain injury (TBI) has affected over 230,000
U.S. service members through the conflicts in Iraq and Afghanistan, mostly as a
result of exposure to blast events. Blast-induced TBI (bTBI) is multi-phasic,
with the penetrating and inertia-driven phases having been extensively studied.
The effects of primary blast injury, caused by the shockwave interacting with the
brain, remain unclear. Earlier in vivo studies in mice and rats have reported
mixed results for primary blast effects on behavior and memory. Using a
previously developed shock tube and in vitro sample receiver, we investigated the
effect of isolated primary blast on the electrophysiological function of rat
organotypic hippocampal slice cultures (OHSC). We found that pure primary blast
exposure inhibited long-term potentiation (LTP), the electrophysiological
correlate of memory, with a threshold between 9 and 39 kPa.ms impulse. This
deficit occurred well below a previously identified threshold for cell death (184
kPa.ms), supporting our previously published finding that primary blast can cause
changes in brain function in the absence of cell death. Other functional measures
such as spontaneous activity, network synchronization, stimulus-response curves,
and paired-pulse ratios (PPRs) were less affected by primary blast exposure, as
compared with LTP. This is the first study to identify a tissue-level tolerance
threshold for electrophysiological changes in neuronal function to isolated
primary blast.
PMID- 26414013
TI - Single Molecule Cluster Analysis dissects splicing pathway conformational
dynamics.
AB - We report Single Molecule Cluster Analysis (SiMCAn), which utilizes hierarchical
clustering of hidden Markov modeling-fitted single-molecule fluorescence
resonance energy transfer (smFRET) trajectories to dissect the complex
conformational dynamics of biomolecular machines. We used this method to study
the conformational dynamics of a precursor mRNA during the splicing cycle as
carried out by the spliceosome. By clustering common dynamic behaviors derived
from selectively blocked splicing reactions, SiMCAn was able to identify the
signature conformations and dynamic behaviors of multiple ATP-dependent
intermediates. In addition, it identified an open conformation adopted late in
splicing by a 3' splice-site mutant, invoking a mechanism for substrate
proofreading. SiMCAn enables rapid interpretation of complex single-molecule
behaviors and should prove useful for the comprehensive analysis of a plethora of
dynamic cellular machines.
PMID- 26414014
TI - Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry.
AB - We describe an integrated workflow that robustly identifies cross-links from
endogenous protein complexes in human cellular lysates. Our approach is based on
the application of mass spectrometry (MS)-cleavable cross-linkers, sequential
collision-induced dissociation (CID)-tandem MS (MS/MS) and electron-transfer
dissociation (ETD)-MS/MS acquisitions, and a dedicated search engine, XlinkX,
which allows rapid cross-link identification against a complete human proteome
database. This approach allowed us to detect 2,179 unique cross-links (1,665
intraprotein cross-links at a 5% false discovery rate (FDR) and 514 interprotein
cross-links at 1% FDR) in HeLa cell lysates. We validated the confidence of our
cross-linking results by using a target-decoy strategy and mapping the observed
cross-link distances onto existing high-resolution structures. Our data provided
new structural information about many protein assemblies and captured dynamic
interactions of the ribosome in contact with different elongation factors.
PMID- 26414015
TI - The costs and effectiveness of large Phase III pre-licensure vaccine clinical
trials.
AB - Prior to the 1980s, most vaccines were licensed based upon safety and
effectiveness studies in several hundred individuals. Beginning with the
evaluation of Haemophilus influenzae type b conjugate vaccines, much larger pre
licensure trials became common. The pre-licensure trial for Haemophilus
influenzae oligosaccharide conjugate vaccine had more than 60,000 children and
that of the seven-valent pneumococcal conjugate vaccine included almost 38,000
children. Although trial sizes for both of these studies were driven by the
sample size required to demonstrate efficacy, the sample size requirements for
safety evaluations of other vaccines have subsequently increased. With the
demonstration of an increased risk of intussusception following the Rotashield
brand rotavirus vaccine, this trend has continued. However, routinely requiring
safety studies of 20,000-50,000 or more participants has two major downsides.
First, the cost of performing large safety trials routinely prior to licensure of
a vaccine is very large, with some estimates as high at US$200 million euros for
one vaccine. This high financial cost engenders an opportunity cost whereby the
number of vaccines that a company is willing or able to develop to meet public
health needs becomes limited by this financial barrier. The second downside is
that in the pre-licensure setting, such studies are very time consuming and delay
the availability of a beneficial vaccine substantially. One might argue that in
some situations, this financial commitment is warranted such as for evaluations
of the risk of intussusception following newer rotavirus vaccines. However, it
must be noted that while an increased risk of intussusception was not identified
in large pre-licensure studies, in post marketing evaluations an increased risk
of this outcome has been identified. Thus, even the extensive pre-licensure
evaluations conducted did not identify an associated risk. The limitations of
large Phase III trials have also been demonstrated in efficacy trials. Notably,
pre-licensure trials of pneumococcal conjugate severely underestimated their true
effect and cost-effectiveness. In fact, in discussions prior to vaccine
introduction in the USA for PCV7, the vaccine was said to be not cost-effective
and some counseled against its introduction. In reality, following introduction,
PCV7 has been shown to be highly cost-effective. In the last decade, new methods
have been identified using large linked databases such as the Vaccine Safety
Datalink in the USA that allow identification of an increased risk of an event
within a few months of vaccine introduction and that can screen for unanticipated
very rare events as well. In addition, the availability of electronic medical
records and hospital discharge data in many settings allows for accurate
assessment of vaccine effectiveness. Given the high financial and opportunity
cost of requiring large pre-licensure safety studies, consideration could be
given to 'conditional licensure' of vaccines whose delivery system is well
characterized in a setting where sophisticated pharmacovigilance systems exist on
the condition that such licensure would incorporate a requirement for rapid cycle
and other real-time evaluations of safety and effectiveness following
introduction. This would actually allow for a more complete and timely evaluation
of vaccines, lower the financial barrier to development of new vaccines and thus
allow a broader portfolio of vaccines to be developed and successfully
introduced.
PMID- 26414016
TI - Coated-Platelet Levels Increase with Number of Injuries in Patients with Mild
Traumatic Brain Injury.
AB - Coated-platelets are procoagulant platelets that are elevated in stroke and are
associated with stroke recurrence. In a previous study, prompted by data showing
an increased risk for stroke following traumatic brain injury (TBI), we found
that coated-platelet levels are elevated in patients with combat-related mild TBI
(mTBI) several years after the injury, compared with controls. We now investigate
in an expanded patient population whether parameters commonly recorded in mTBI
are related to increased coated-platelet potential. Coated-platelet levels were
assayed in 120 mTBI patients at intervals ranging from 6 months to 10 years from
the last injury. Correlations were calculated between coated-platelet levels and
age, gender, race/ethnicity, loss of consciousness, alteration in consciousness,
post-traumatic amnesia, number of injuries, mechanism of injury, time since first
and last injury, smoking, medications that may influence coated-platelet levels,
and pertinent comorbid conditions. Significant correlations were detected between
coated-platelet levels and number of injuries (p = 0.026), gender (p = 0.01), and
time since last injury (p = 0.04). A multi-variable linear model analysis,
including these three parameters and an additional three parameters
(race/ethnicity, smoking, and mechanism of injury) that reached a p value of
<0.2, showed that the number of injuries were predictive of coated-platelet
levels (p = 0.004). These results support a mechanistic link between increased
coated-platelet levels and repeated injuries in mTBI. Long-term studies will be
required to determine the impact of increased prothrombotic potential in mTBI
patients.
PMID- 26414018
TI - Image Generation Using Bidirectional Integral Features for Face Recognition with
a Single Sample per Person.
AB - In face recognition, most appearance-based methods require several images of each
person to construct the feature space for recognition. However, in the real world
it is difficult to collect multiple images per person, and in many cases there is
only a single sample per person (SSPP). In this paper, we propose a method to
generate new images with various illuminations from a single image taken under
frontal illumination. Motivated by the integral image, which was developed for
face detection, we extract the bidirectional integral feature (BIF) to obtain the
characteristics of the illumination condition at the time of the picture being
taken. The experimental results for various face databases show that the proposed
method results in improved recognition performance under illumination variation.
PMID- 26414017
TI - Impact of Hydroxychloroquine on Atherosclerosis and Vascular Stiffness in the
Presence of Chronic Kidney Disease.
AB - Cardiovascular disease is the largest cause of morbidity and mortality among
patients with chronic kidney disease (CKD) and end-stage kidney disease, with
nearly half of all deaths attributed to cardiovascular disease.
Hydroxychloroquine (HCQ), an anti-inflammatory drug, has been shown to have
multiple pleiotropic actions relevant to atherosclerosis. We conducted a proof-of
efficacy study to evaluate the effects of hydroxychloroquine in an animal model
of atherosclerosis in ApoE knockout mice with and without chronic kidney disease.
Forty male, 6-week-old mice were divided into four groups in a 2 x 2 design: sham
placebo group; sham treatment group; CKD placebo group; and CKD treatment group.
CKD was induced by a two-step surgical procedure. All mice received a high-fat
diet through the study duration and were sacrificed after 16 weeks of therapy.
Mice were monitored with ante-mortem ultrasonic echography (AUE) for
atherosclerosis and vascular stiffness and with post-mortem histology studies for
atherosclerosis. Therapy with HCQ significantly reduced the severity of
atherosclerosis in CKD mice and sham treated mice. HCQ reduced the area of aortic
atherosclerosis on en face examination by approximately 60% in HCQ treated groups
compared to the non-treated groups. Additionally, therapy with HCQ resulted in
significant reduction in vascular endothelial dysfunction with improvement in
vascular elasticity and flow patterns and better-preserved vascular wall
thickness across multiple vascular beds. More importantly, we found that presence
of CKD had no mitigating effect on HCQ's anti-atherosclerotic and
vasculoprotective effects. These beneficial effects were not due to any
significant effect of HCQ on inflammation, renal function, or lipid profile at
the end of 16 weeks of therapy. This study, which demonstrates structural and
functional protection against atherosclerosis by HCQ, provides a rationale to
evaluate its use in CKD patients. Further studies are needed to define the exact
mechanisms through which HCQ confers these benefits.
PMID- 26414020
TI - Behavioral Programs for Type 1 Diabetes Mellitus: A Systematic Review and Meta
analysis.
AB - BACKGROUND: Whether behavioral approaches for self-management programs benefit
individuals with type 1 diabetes mellitus is unclear. PURPOSE: To determine the
effects of behavioral programs for patients with type 1 diabetes on behavioral,
clinical, and health outcomes and to investigate factors that might moderate
effect. DATA SOURCES: 6 electronic databases (1993 to June 2015), trial
registries and conference proceedings (2011 to 2014), and reference lists. STUDY
SELECTION: 36 prospective, controlled studies involving participants of any age
group that compared behavioral programs with usual care, active controls, or
other programs. DATA EXTRACTION: One reviewer extracted and another verified
data. Two reviewers assessed quality and strength of evidence (SOE). DATA
SYNTHESIS: Moderate SOE showed reduction in glycated hemoglobin (HbA1c) at 6
months after the intervention compared with usual care (mean difference, -0.29
[95% CI, -0.45 to -0.13] percentage points) and compared with active controls (
0.44 [CI, -0.69 to -0.19] percentage points). At the end of the intervention and
12-month follow-up or longer, there were no statistically significant differences
in HbA1c (low SOE) for comparisons with usual care or active control. Compared
with usual care, generic quality of life at program completion did not differ
(moderate SOE). Other outcomes had low or insufficient SOE. Adults appeared to
benefit more for glycemic control at program completion (-0.28 [CI, -0.57 to
0.01] percentage points) than did youth (-0.12 [CI, -0.43 to 0.19] percentage
points). Program intensity appeared not to influence effectiveness; some
individual delivery appears beneficial. LIMITATIONS: All studies had medium or
high risk of bias. There was scarce evidence for many outcomes. CONCLUSION:
Behavioral programs for type 1 diabetes offer some benefit for glycemic control,
at least at short-term follow-up, but improvement for other outcomes has not been
shown. (PROSPERO registration number: CRD42014010515). PRIMARY FUNDING SOURCE:
Agency for Healthcare Research and Quality. (PROSPERD registration number:
CRD42014010515).
PMID- 26414019
TI - Areca nut alkaloids induce irreparable DNA damage and senescence in fibroblasts
and may create a favourable environment for tumour progression.
AB - BACKGROUND: Oral submucous fibrosis (OSMF) is a pre-malignant condition that is
strongly associated with the areca nut alkaloids, arecoline (ARC) and arecaidine
(ARD). The condition is characterised by the presence of senescent fibroblasts in
the subepithelial mesenchyme which have the potential to promote malignancy in
the neighbouring epithelial cells. We tested the hypothesis that areca nut
alkaloids induce senescence in oral fibroblasts and promote the secretion of
invasion-promoting transforming growth factor beta (TGF-beta) and matrix
metalloproteinase-2 (MMP-2). METHODS: Two oral fibroblast lines were treated for
48h with ARC and ARD. Senescence-associated beta-galactosidase (SA-betaGal)
activity, Ki67 (cycling cells), large 53BP1 foci (irreparable DNA strand breaks)
and p16(INK) (4A) (late senescence) were used as markers of cellular senescence
and were quantified using indirect immunofluorescence and the ImageJ program. TGF
beta and MMP-2 levels were measured using ELISA. Statistical analyses were
performed with the two-tailed unpaired t-test where n = 3 and the Wilcoxon-Mann
Whitney test where n = 6. RESULTS: ARC (100 and 300 MUM) and ARD (30 and 100 MUM)
significantly (P < 0.05) induced fibroblast senescence, as determined by the
increased expression of SA-betaGal, 53BP1 staining and CDKN2A/p16(INK) (4A) ;
there was also a non-significant reduction in Ki67 staining. Treated cells also
showed a three- fivefold increase in TGF-beta and a small non-significant
increase in MMP-2. CONCLUSIONS: Areca nut alkaloids induce senescence in oral
fibroblasts and promote increased secretion of TGF-beta and perhaps MMP-2 that
may create a tissue environment thought to be critical in the progression of OSMF
to malignancy.
PMID- 26414021
TI - Curcumin raises lipid content by Wnt pathway in hepatic stellate cell.
AB - BACKGROUND: Activation of hepatic stellate cells (HSCs) is a pivotal event in
liver fibrosis, which is characterized by dramatic disappearance of lipid
droplets. However, the underlying molecular mechanisms are largely unknown. We
aimed to explore the role of Wnt/beta-catenin pathway in HSC lipogenesis and to
examine the effects of curcumin in this molecular context. METHODS: Primary rat
HSCs were cultured in vitro for experiments. The Wnt activator WAY-262611 and
beta-catenin activator lithium chloride (LiCl) were used to activate the pathway
at distinct levels in HSCs. Cell proliferation, fibrogenic markers, intracellular
lipids and triglyceride, and adipogenic transcription factors were examined in
HSCs. RESULTS: Both WAY-262611 and LiCl promoted proliferation and upregulated
the expression of alpha-smooth muscle actin and alpha1(I) procollagen, but they
decreased the contents of intracellular lipids and triglyceride in HSCs. Analyses
of adipogenic transcription pattern showed that the two compounds reduced the
expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer
binding protein alpha, retinoid X receptor-alpha, and retinoic acid receptor
beta, four key transcription regulators of HSC adipogenic phenotype. Curcumin
also reduced the expression of Frizzled and beta-catenin, upregulated the
expression of adipogenic transcription factors, and restored lipid content in
HSCs. However, both WAY-262611 and LiCl abrogated curcumin restoration of
lipogenesis and inhibition of fibrogenic marker expression in HSCs. CONCLUSIONS:
Wnt/beta-catenin pathway was a profibrogenic signaling and inhibited lipogenesis
by suppressing adipogenic transcription pattern in HSCs. Blockade of this pathway
was associated with curcumin stimulation of HSC lipogenesis. We revealed a novel
mechanism underlying curcumin restoration of lipid droplets during HSC
activation.
PMID- 26414023
TI - Sensitive and rapid detection of pathogenic bacteria in small volumes using
impedance spectroscopy technique.
AB - We illustrate a novel impedance immunosensor which rapidly and sensitively
detects typhoid-causing infectious bacteria Salmonella enterica serovar
(Salmonella typhi) in 10 MUL of sample volume. The bacteria are tagged with gold
nanoparticles (Au NPs) via high-affinity antigen-antibody interactions for
enhanced signal amplification and selectivity. The cell-particle bioconjugates
are then subjected to alternating current (AC) electric fields applied through
interdigitated microelectrodes. The immunosensor performance is optimized with
respect to electric field frequency, cell concentration, incubation times and the
type of blocking agent to achieve a low limit of detection (LOD) of 100 CFU/mL.
The approach is extendable to a wide spectrum of clinical diseases and offers an
efficient and cost-effective solution for point-of-care diagnosis.
PMID- 26414022
TI - Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical
Trial.
AB - IMPORTANCE: Early identification of Alzheimer disease (AD) is important for
clinical management and affords the opportunity to assess potential disease
modifying agents in clinical trials. To our knowledge, this is the first report
of a randomized trial to prospectively enrich a study population with prodromal
AD (PDAD) defined by cerebrospinal fluid (CSF) biomarker criteria and mild
cognitive impairment (MCI) symptoms. OBJECTIVES: To assess the safety of the
gamma-secretase inhibitor avagacestat in PDAD and to determine whether CSF
biomarkers can identify this patient population prior to clinical diagnosis of
dementia. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled
phase 2 clinical trial with a parallel, untreated, nonrandomized observational
cohort of CSF biomarker-negative participants was conducted May 26, 2009, to July
9, 2013, in a multicenter global population. Of 1358 outpatients screened, 263
met MCI and CSF biomarker criteria for randomization into the treatment phase.
One hundred two observational cohort participants who met MCI criteria but were
CSF biomarker-negative were observed during the same study period to evaluate
biomarker assay sensitivity. INTERVENTIONS: Oral avagacestat or placebo daily.
MAIN OUTCOMES AND MEASURE: Safety and tolerability of avagacestat. RESULTS: Of
the 263 participants in the treatment phase, 132 were randomized to avagacestat
and 131 to placebo; an additional 102 participants were observed in an untreated
observational cohort. Avagacestat was relatively well tolerated with low
discontinuation rates (19.6%) at a dose of 50 mg/d, whereas the dose of 125 mg/d
had higher discontinuation rates (43%), primarily attributable to
gastrointestinal tract adverse events. Increases in nonmelanoma skin cancer and
nonprogressive, reversible renal tubule effects were observed with avagacestat.
Serious adverse event rates were higher with avagacestat (49 participants
[37.1%]) vs placebo (31 [23.7%]), attributable to the higher incidence of
nonmelanoma skin cancer. At 2 years, progression to dementia was more frequent in
the PDAD cohort (30.7%) vs the observational cohort (6.5%). Brain atrophy rate in
PDAD participants was approximately double that of the observational cohort.
Concordance between abnormal amyloid burden on positron emission tomography and
pathologic CSF was approximately 87% (kappa = 0.68; 95% CI, 0.48-0.87). No
significant treatment differences were observed in the avagacestat vs placebo arm
in key clinical outcome measures. CONCLUSIONS AND RELEVANCE: Avagacestat did not
demonstrate efficacy and was associated with adverse dose-limiting effects. This
PDAD population receiving avagacestat or placebo had higher rates of clinical
progression to dementia and greater brain atrophy compared with CSF biomarker
negative participants. The CSF biomarkers and amyloid positron emission
tomography imaging were correlated, suggesting that either modality could be used
to confirm the presence of cerebral amyloidopathy and identify PDAD. TRIAL
REGISTRATION: clinicaltrials.gov Identifier: NCT00890890.
PMID- 26414024
TI - Label-free DNA Y junction for bisphenol A monitoring using exonuclease III-based
signal protection strategy.
AB - A label-free DNA Y junction sensing platform for the amplified detection of
bisphenol A (BPA) has been constructed by the ingenious combination of toehold
mediated strand displacement and exonuclease III (Exo III)-based signal
protection strategy. Three hairpin probes were utilized as the building blocks to
fabricate the DNA Y junction with cascaded signal amplification via a series of
toehold-mediated strand displacement reactions. Exo III was employed as a
protecting agent for the first time to keep the Y-shaped molecular architecture
intact, thereby greatly enhancing the fluorescence intensity of DNA intercalator
SYBR Green I. The resulting biosensor exhibits ultrasensitivity towards BPA at
low concentration (5 fM) without any labeling, modification, immobilization, or
washing procedure. Our proposed sensing system also displays remarkable
specificity to BPA against other possible interference molecules. Moreover, this
DNA junction biosensor is robust and can be applied to the reliable monitoring of
spiked BPA in environmental water samples with good recovery and accuracy. With
the successful demonstration for BPA detection, the label-free DNA Y junction can
be readily expanded to monitor other analytes in a simple, cost-effective, and
ultrasensitive way by substituting the target-specific aptamer sequence.
PMID- 26414025
TI - Leverage principle of retardation signal in titration of double protein via chip
moving reaction boundary electrophoresis.
AB - In the present work we address a simple, rapid and quantitative analytical method
for detection of different proteins present in biological samples. For this, we
proposed the model of titration of double protein (TDP) and its relevant leverage
theory relied on the retardation signal of chip moving reaction boundary
electrophoresis (MRBE). The leverage principle showed that the product of the
first protein content and its absolute retardation signal is equal to that of the
second protein content and its absolute one. To manifest the model, we achieved
theoretical self-evidence for the demonstration of the leverage principle at
first. Then relevant experiments were conducted on the TDP-MRBE chip. The results
revealed that (i) there was a leverage principle of retardation signal within the
TDP of two pure proteins, and (ii) a lever also existed within these two complex
protein samples, evidently demonstrating the validity of TDP model and leverage
theory in MRBE chip. It was also showed that the proposed technique could provide
a rapid and simple quantitative analysis of two protein samples in a mixture.
Finally, we successfully applied the developed technique for the quantification
of soymilk in adulterated infant formula. The TDP-MRBE opens up a new window for
the detection of adulteration ratio of the poor food (milk) in blended high
quality one.
PMID- 26414027
TI - [The changing face of public health in Quebec].
PMID- 26414026
TI - Highly selective and sensitive surface enhanced Raman scattering nanosensors for
detection of hydrogen peroxide in living cells.
AB - Determination of hydrogen peroxide (H2O2) with high sensitivity and selectivity
in living cells is a challenge for evaluating the diverse roles of H2O2 in the
physiological and pathological processes. In this work, we present novel surface
enhanced Raman scattering (SERS) nanosensors, 4-carboxyphenylboronic acid (4-CA)
modified gold nanoparticles (Au NPs/4-CA), for sensing H2O2 in living cells. The
nanosensors are based on that the H2O2-triggered oxidation reaction with the
arylboronate on Au NPs would liberate the phenol, thus causing changes of the
SERS spectra of the nanosensors. The results show the nanosensors feature higher
selectivity for H2O2 over other reactive oxygen species, abundant competing
cellular thiols and biologically relevant species, as well as excellent
sensitivity with a low detection limit of 80 nM, which fulfills the requirements
for detection of H2O2 in a biological system. In addition, the SERS nanosensors
exhibit long term stability against time and pH, and high biocompatibility. More
importantly, the presented nanosensors can be successfully used for monitoring
changes of H2O2 levels within living biological samples upon oxidative stress,
which opens up new opportunities to study its cellular biochemistry.
PMID- 26414028
TI - [Immunization educational game in general practice waiting rooms. A comparative
study].
AB - INTRODUCTION: The general practitioner's (GP) waiting room is an ideal place to
conduct health education actions. The use of tools in GP waiting rooms would
appear to be a useful approach, but the available tools are not very efficient.
The objective of this study was to study the efficacy of a game compared with two
other health education strategies. METHODS: A comparative study was conducted in
two general practices. 212 patients were divided into three groups using a paper
game or a booklet or nothing in the waiting room, before a discussion about
immunization with the practitioner. The capacity of the tool to encourage
questions about immunization was estimated by the GP at the end of the
consultation by a questionnaire. RESULTS: The use of a tool in the waiting room
facilitated the discussion between patients and practitioners (34% vs 12%,
p<0.01). The game induced longer discussions than the booklet (1 minute 32
seconds vs 1 minute 14 seconds, p<0.05) without more themes. The game and the
booklet had a comparable acceptability. CONCLUSIONS: Using a multistep education
strategy facilitated discussion between the patient and the practitioner.
However, the GP is required to trigger the conversation.
PMID- 26414029
TI - [Assessment of smoking cessation assistance in French pharmacies].
AB - INTRODUCTION: While smoking continues to kill 73,000 people each year in France,
new legislation allows pharmacists to ensure public health actions. How do
pharmacists contribute to smoking cessation? METHODS: This study described
smoking cessation professional practices, the tests used and dispensing of
nicotine replacement therapy based on an online questionnaire administered to a
random sample of 220 pharmacists, selected from the "Ordre des pharmaciens"
website. The questionnaire concerned the type of pharmacy, place of smoking
cessation support, knowledge and application of tests, training, referral to the
physician and dispensing of nicotine replacement therapy. RESULTS: Among the 133
respondent pharmacies, minimal intervention and the Fagerstrom test were two
tools most commonly used and 82.7% of pharmacists advised nicotine replacement
therapy. Practices complied with guidelines, although certain dispensing
difficulties were identified, as well as somewhat approximate or even incorrect
knowledge concerning the dispensing of nicotine replacement therapy for certain
patients (coronary heart disease, pregnant and breastfeeding women, teenagers).
DISCUSSION: Certain improvements can be proposed such as the use of a
confidential place for private conversations, better patient follow-up, better
training and improvement of good practices by young pharmacists.
PMID- 26414030
TI - [Psychosocial work factors and self-reported health in the French national SUMER
survey].
AB - INTRODUCTION: This study was designed to investigate the associations between
psychosocial work factors, using well-known theoretical models and emerging
concepts, and self-reported health in the national population of French
employees. METHODS: This study was based on the data of the French national
representative SUMER 2010 survey. The sample included 46,962 employees, 26,883
men and 20,079 women, with an 87% participation rate. Self-reported health was
measured by means of a single question and was analysed as a binary variable.
Psychosocial work factors included factors related to job strain and effort
reward imbalance models, workplace violence and working hours. Associations
between psychosocial work factors and self-reported health were studied using
weighted logistic regression models adjusted for covariates (age, occupation,
economic activity, and other types of occupational exposure). RESULTS: Low
decision latitude (skill discretion and decision authority), high psychological
demands, low social support (from supervisors for men), low reward (low esteem
and low job promotion for both genders and job insecurity for men), bullying and
verbal abuse for both genders were associated with self-reported health.
CONCLUSIONS: This study emphasizes the role of psychosocial work factors as risk
factors for poor self-reported health and suggests that the implementation of
preventive measures to reduce exposure to psychosocial work factors should be an
objective for the improvement of health at work.
PMID- 26414031
TI - [From professional practice assessment to continuing professional development:
hospital practitioners' involvement and opinion concerning professional practice
assessment activities].
AB - INTRODUCTION: The aim of this study was to describe implementation of
professional practice assessment (PPA) programmes and participation of physicians
and pharmacists in these programmes in a French university hospital. METHODS: We
conducted an observational study based on PPA programmes validated in Grenoble
university hospital continuing education board between 2007 and 2011. Data were
extracted from individual commitment forms filled in by professionals and
programme validation forms. The main outcome was the proportion of full-time
hospital practitioners who validated at least one PPA programme. RESULTS: Over a
5-year period, 64 PPA programmes and 509 individual commitments involving 366
professionals were validated. At study endpoint, 264 (47%) permanent
professionals had validated their mandatory PPA programme. The main methods used
in PPA programmes included mortality and morbidity reviews (23),
multidisciplinary meetings (23), staff PPA (8) and experience feedback committees
(6). The most commonly reported strengths of these programmes included team work
(49%) and improvement of patient care (30%). The most commonly reported drawbacks
were organizational issues (27%) and unavailability to participate (23%).
CONCLUSION: Hospital practitioners and pharmacists adhered to team-based PPA
programmes. Implementation of team-base continuing development programmes was the
preferred modality during the study period. Implementation of continuing
professional development should help support this dynamic.
PMID- 26414032
TI - [Arduous working conditions for beginners: when workplace prevention becomes an
economic risk].
AB - The French law of 20.01.2014 recently instituted an arduous working conditions
allowance. This innovated legislation is designed to improve the status of
workers subject to arduous working conditions either by allowing lighter work
schedules or job reclassification or early retirement. The impact of arduous
working conditions on health has been clearly established, but no consensual
solution has yet been proposed. Life expectancy without disability can differ by
as much as 9 years between higher executives and manual workers, but the proposed
solutions comprise a multitude of perverse effects. Workers may benefit from
maintaining their arduous working conditions in order to preserve their right to
early retirement. Companies do not necessarily have the desire or the resources
to invest in prevention, which is the only consensually accepted effective
measure, if they are also required to finance both training and retirement. In
particular, management of the arduous working conditions allowance is very
complex and entirely financed by companies. Consequently, company productivity
can be impacted, leading to transfers of company headquarters, outsourcing to
interim workers, replacement of jobs by automation. Unemployment could be the big
winner of this conflict. Politically, arduous working conditions allowance
appears to be very difficult to put into practice and can be considered to be
more a promise by the government to the left and to the trade unions.
PMID- 26414033
TI - [Palliative care practices in residential facilities for the elderly requiring
full-time care].
AB - AIMS: The purpose of this study was to assess palliative care practices for
residents of Larmont residential facilities for the elderly requiring full-time
care (Doubs, France) throughout their stay. METHODS: This was a healthcare peer
review based on a retrospective clinical audit in compliance with the
recommendations of the French Health Authority. The 252-bed Larmont residential
care facilities for the elderly is a public institution, attached to the local
Hospital. The 72 residents of the Larmont residential care facilities for the
elderly who died during 2012 were included in the study. RESULTS: Death occurred
on the premises for 95.8 percent of residents. The proposal to appoint a support
person was recorded in 27.6 percent of audited cases. End-of-life instructions
were recorded in 23.2 percent of cases. In 31.8 percent of cases, the medical
record referred to a multidisciplinary procedure, which complied with regulations
in less than one half of cases. The residents' pain at the end of their life was
insufficiently assessed and managed. A discomfort other than pain was identified
in 89.2 percent of cases. CONCLUSIONS: This healthcare peer review led to a
quality improvement plan focusing on three areas : ensure that medical practices
are in line with patients' rights, anticipate identification of the end of life
and improve management of pain and suffering at the end of life.
PMID- 26414034
TI - [Impact on professional practices of a care protocol implemented between usual
hospital care and hospital at home].
AB - BACKGROUND: Implementation of a care protocol between usual hospital care and
hospital at home (HAH) could improve the quality of care and decrease
fragmentations of the French healthcare system. This study evaluated the impact
on professional practices of a care protocol implemented between a surgery unit
and hospital at home. METHODS: Twenty healthcare professionals (nurses, head
nurses, physicians) from HAH and a Paris public hospital urology unit were
interviewed by a public heath physician. Semistructured interviews were analyzed
using the grounded theory. RESULTS: Professional practices were modified with
better traceability of care, greater safety for professionals and for patients,
standardization of practices and improved continuity of interventions between
hospital and hospital at home. However, these changes in practices appeared to be
limited to the protocol itself and indicated potential enhancement of technical
aspects to the detriment of human contact. CONCLUSION: This care protocol has an
encouraging impact on the quality of care. These results demonstrate the value of
extending this approach to other wards to improve continuity of care between
usual hospital care and hospital at home.
PMID- 26414035
TI - [Organized or individual breast cancer screening: what motivates women?].
AB - OBJECTIVE: The breast cancer screening programme, proposed to all women between
50 and 69 years, consisting of two-view mammography screening every two years,
has been generalized in France since 2004. The programme coexists with
opportunistic mammography screening, provided outside official frameworks. This
qualitative study was designed to identify the pros and cons of these two
screening modes. METHODS: Three hundred and forty-five women were randomly
selected from women who had participated in a previous quantitative study and who
were invited to attend for breast cancer screening in 13 French departments
between 2010 and 2011. These women were asked to participate in a face-to-face
semistructured interview conducted by a sociologist. RESULTS: 48 women (17 from
deprived areas) were interviewed. All chose to be screened for breast cancer
either because they feared cancer, or because they wanted to control their own
health. Twenty-seven women chose the organized screening programme, which they
considered to be trustworthy, as negative mammograms are double checked by a
second radiologist. Twenty-one women preferred individual screening, which they
considered to be more reliable, less anonymous and providing them with more
liberty to take control of their own health. CONCLUSION: Gynaecologists play an
important role in women's decision to undergo individual breast cancer screening.
They also have an important role to play in the promotion of organized breast
cancer screening programme with this public.
PMID- 26414036
TI - [Frequency and coding of psychiatric care of short-stay patients].
AB - INTRODUCTION: The objective of this study was to describe the frequency and
coding of the psychiatric management of short-stay patients admitted to Nice
University Hospital in 2013. METHODS: Various parameters were measured :
percentage of outpatient psychiatric procedures or psychiatric diagnosis codes ;
coding practice differences between the Programme de medicalisation des systemes
d'information (Medical Information System Programme) for medicine, surgery and
obstetrics and psychiatric medical data records, and the impact of coding on
diagnosis-related groups. RESULTS: Twenty-four per cent of hospitalised patients
received psychiatric management (either outpatient care or a psychiatric
diagnosis) and 3.9% received both psychiatric management and a psychiatric
diagnosis. Liaison psychiatrists more commonly used codes for neurotic and
psychosomatic disorders (28% vs 16%), while somatic physicians more commonly used
codes for psychoactive substance use-related disorders (26% vs 16%).The presence
of psychiatric comorbidity had an impact on the DRG classification or the level
of severity for 0.5% of standardized discharge summaries. CONCLUSION: This study
illustrates the importance of the active involvement of psychiatry personnel in
the management of short-stay patients. The importance of psychosomatic medicine
in a short-stay institution could be improved by establishing a clearer
definition of coding rules for these diseases and revising and identifying wards
or beds devoted to psychosomatic disorders.
PMID- 26414038
TI - [Health workers' involvement for data quality improvement in Benin].
AB - OBJECTIVE: In developing countries, the poor quality of data derived from Health
Information Systems constitutes a problem that limits use of these data and
contributes to the recurrent difficulties of health system management. The low
level of involvement of health workers directly responsible for data may
contribute to this poor quality. This study documents a Health Information System
collection tool design experience by health workers and assesses its effect on
data quality. METHODS: Eighty health workers responsible for clinical statistics
in public health centres participated in this study. The two tools used for
clinical data collection were modified by a group of 6 volunteer health workers.
Monitoring indicators, data entry time, percentage exhaustiveness and quality of
data were assessed before and after using the new tools. Data were compared by
Wilcoxon's test for paired data and Mc Nemar's chi-square test. RESULTS: Between
the two assessments, the data entry time increased from 28.7 to 22.5 seconds by
reported case (p=0.153), the exhaustiveness of the reports increased from 16% to
89% (p<0.001) and the proportion of reports with sufficient data quality
increased from 18.8% to 45.8% (p=0.002). CONCLUSION: The positive course of the
indicators shows that increased involvement of health workers in key stages such
as the design of data collection tools can help improve data quality.
PMID- 26414037
TI - [Is there room for improvement in the field of dental ethics?].
AB - INTRODUCTION: Dental ethics, enforced by the Dental Board, are defined in the
Code of Conduct for dentists included in the French Public Health Code. Dentist
patient relationships are changing, while scientific progress advances more
rapidly than dental ethics. Are dental ethics still adapted to the practice of
dentistry? METHODS: This study was based on the Institut BVA "The French and
patients' rights" survey conducted in September 2013, together with a systematic
review of the literature using the Medline, Legifrance, Lexisnexis, and Elnet.fr
databases and the Paris Descartes University medical library website. RESULTS:
Five essential principles were identified and a total of 210 articles were
included. The results indicate that there is room for improvement in pain
management, respect of human dignity, information and consent concerning
healthcare, and free choice of a practitioner. CONCLUSION: Dental ethics have
evolved, but further improvement is required to adapt the dentist-patient
relationship to scientific progress and the patients' expectations. To ensure a
truly informed choice, this article shows that dental ethics cannot vary in
response to surveys or fashions, as dental practice must remain essentially based
on an ethical approach that cannot be rigidly defined in a code of professional
conduct.
PMID- 26414039
TI - [Antibiotic consumption at Antananarivo University Hospital: prevalence and
strategic challenges].
AB - INTRODUCTION: Very few studies have been conducted on antibiotic consumption in
Madagascar. The objective of this study was to describe antibiotic consumption in
a tertiary university hospital in Antananarivo, Madagascar to more clearly define
good antibiotic use strategies. MATERIALS AND METHOD: A one-day prevalence survey
was conducted on 5 April 2011 in the 339-bed Befelatanana Hospital with a bed
occupation rate of 65.5%. RESULTS: The prevalence of antibiotic therapy among the
222 patients hospitalised on the day of the survey was 57.2%. Almost one half
(49.6%) of patients received a combination of at least two antibiotics. The
classes of antibiotics most commonly prescribed were beta-lactam antibiotics
(55.3%), imidazoles (14.9%), aminoglycosides (14.9%), quinolones (7.9%) and
macrolides with 7% of prescriptions. Penicillins accounted for 55.5% of all beta
lactam antibiotic prescriptions, followed by third-generation cephalosporins.
Children under the age of 14 years (p<0.019) and patients with invasive devices
(p<10(-6)) received more antibiotics. Antibiotic prescription in the Emergency
Room-Intensive Care Unit was significantly higher than in the other wards
(p<0.01). CONCLUSION: A high rate of antibiotic use was observed in Befelatanana
University Hospital. Beta-lactam antibiotics were the agents most commonly
prescribed and the Emergency Room-Intensive Care Unit was the leading antibiotic
prescriber. It is essential to set up a good antibiotic use policy.
PMID- 26414041
TI - [Evaluation of application of national guidelines for the management of malaria
in Bobo-Dioulasso university hospital].
AB - INTRODUCTION: To evaluate compliance with national guidelines concerning the
diagnosis and treatment of malaria at Souro Sanou university hospital in Bobo
Dioulasso. METHODS: This was a cross-sectional descriptive study based on the
medical records of patients hospitalised in the Medicine and Paediatrics
departments in 2012. All cases labelled as "malaria" on admission and on
discharge, for which the medical records were complete, were included in the
study. RESULTS: Of the total of 1,722 cases collected, 1,674 cases (97.22%) were
labelled as "severe malaria". The mean age of these patients was 2.65 years [95%
CI: 2.41-2.90 years]; 87.63% of cases were under the age of 5 years. The sex
ratio was 1.22. The diagnosis complied with guidelines in 13.82% of cases. The
rate of compliance with the diagnosis did not differ according to the severity of
the disease (p=0.78), but differed according to age-group: 13.12% in subjects
under the age of 5 years versus 18.78% in subjects over the age of 5 years
(p=0.02). Cases labelled as "severe malaria" (SM comprised 1.47% of cases of
"uncomplicated malaria" (UCM); inversely, 4.17% cases of SM were identified among
cases labelled as UCM. Overall, 242 cases (14.05%) were confirmed cases of
malaria versus 1,480 cases (85.95%) of presumed malaria. Treatment complied with
guidelines in 57.49% of cases. The adequate treatment rate was higher for cases
of SM (58.90% versus 8.33%, p<0.01) and in children under the age of 5 years
(58.71% versus 48.30%, p=0.02). CONCLUSION: This study demonstrated poor
compliance with clinical practice guidelines concerning the management of malaria
in Bobo-Dioulasso university hospital. Identification of factors responsible for
poor compliance with these guidelines may help to identify appropriate measures
to improve compliance and contribute to control of malaria in the country.
PMID- 26414040
TI - [Quality of immunization data in children aged 0 to 11 months in Cote d'Ivoire].
AB - INTRODUCTION: In order to guide the decisions of programme managers, an
immunization Data Quality Self-Assessment was performed in Cote d'Ivoire in 2012.
This study was designed to assess the accuracy of immunization data and the
quality of the immunization tracking system with this tool. METHODS: A
descriptive cross-sectional study was conducted in 88 randomly selected
immunization facilities from 30 health districts. These structures were included
in the study based on the number of children aged 0-11 months who received three
doses of vaccine against Diphtheria, Tetanus, Pertussis, Hepatitis B Viral and
Haemophilus Influenzae b on the one hand and measles vaccine coverage on the
other. This assessment focused on two criteria in particular: accuracy of
immunization data measured by the verification factor (VF) and the quality of the
immunization tracking system. RESULTS: The accuracy of immunization data was
satisfactory at the district level (VF=95%), but not for the health centre level
(VF=81%), as 73% of health districts and health centres obtained a satisfactory
factor (>=95%).The number of children aged 0-11 months vaccinated differed from
one level of the health system to another and from one document to another.The
mean quality index was not satisfactory for both the district and health centre
levels (64% vs 50%). Only one health district and one health centre obtained a
quality index greater than 80%. Furthermore, 93% of health districts and 50% of
health centres obtained quality indices ranging from 50% and 80%,
respectively.The weakest components at both levels were "supervision and
monitoring" and "analysis and use of data". CONCLUSION: The deficiencies in data
reporting and the quality of the immunization monitoring system need to be
improved by supportive supervision.
PMID- 26414043
TI - Effect of Playing Video Games on Laparoscopic Skills Performance: A Systematic
Review.
AB - BACKGROUND AND PURPOSE: The advances in both video games and minimally invasive
surgery have allowed many to consider the potential positive relationship between
the two. This review aims to evaluate outcomes of studies that investigated the
correlation between video game skills and performance in laparoscopic surgery.
METHODS: A systematic search was conducted on PubMed/Medline and EMBASE databases
for the MeSH terms and keywords including "video games and laparoscopy,"
"computer games and laparoscopy," "Xbox and laparoscopy," "Nintendo Wii and
laparoscopy," and "PlayStation and laparoscopy." Cohort, case reports, letters,
editorials, bulletins, and reviews were excluded. Studies in English, with task
performance as primary outcome, were included. The search period for this review
was 1950 to December 2014. RESULTS: There were 57 abstracts identified: 4 of
these were found to be duplicates; 32 were found to be nonrelevant to the
research question. Overall, 21 full texts were assessed; 15 were excluded
according to the Medical Education Research Study Quality Instrument quality
assessment criteria. The five studies included in this review were randomized
controlled trials. Playing video games was found to reduce error in two studies
(P 0.002 and P 0.045). For the same studies, however, several other metrics
assessed were not significantly different between the control and intervention
group. One study showed a decrease in the time for the group that played video
games (P 0.037) for one of two laparoscopic tasks performed. In the same study,
however, when the groups were reversed (initial control group became intervention
and vice versa), a difference was not demonstrated (P for peg transfer 1 - 0.465,
P for cobra robe - 0.185). Finally, two further studies found no statistical
difference between the game playing group and the control group's performance.
CONCLUSION: There is a very limited amount of evidence to support that the use of
video games enhances surgical simulation performance.
PMID- 26414045
TI - Building a Culture of Excellence: Learning From Our Successes.
PMID- 26414044
TI - Targeting lipid metabolism for the treatment of anaplastic thyroid carcinoma.
AB - INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is the rarest subtype of thyroid
cancer; however, it disproportionately accounts for a large percentage of all
thyroid cancer-related deaths and is considered one of the most lethal solid
tumors in humans, having a median survival of only a few months upon diagnosis.
Although a variety of treatment options are available including surgery,
radiation and targeted therapies, response rates are low, due in part to the drug
resistant nature of this disease; therefore, new avenues for therapeutic
intervention are surely needed. Recent investigation into the metabolic profile
of ATC has revealed a tumor-specific dependency for increased de novo
lipogenesis, offering new insight into the molecular mechanisms that govern
disease initiation and progression. AREAS COVERED: Herein we summarize known
oncogenic signaling pathways and current therapeutic strategies for the treatment
of ATC. We further discuss the unique expression pattern of lipid metabolism
constituents in this disease. Additionally, the current literature correlating
aberrant lipogenesis with carcinogenesis is reviewed, and the implications of
targeting this pathway as an innovative approach for treating ATC and other
malignancies are discussed. As stearoyl-CoA desaturase (SCD) is the most
differentially expressed constituent of lipid metabolism in ATC, an additional
focus on this enzyme as a novel therapeutic target is applied. EXPERT OPINION:
This section is used to summarize the current research efforts underway in
defining the role of lipid metabolism specifically in thyroid carcinoma. Included
is a brief summary of lipid metabolism factors for which inhibitors have been
generated and are under current investigation as anti-cancer agents. Finally,
research limitations regarding the use of these inhibitors against components of
this pathway are discussed.
PMID- 26414046
TI - Health Policy in Medical Education: A Renewed Look at a Timely and Achievable
Imperative.
PMID- 26414047
TI - In Reply to Kagan and Armstrong.
PMID- 26414048
TI - Discordance Persists Between Trainers' and Trainees' Perceptions of Workplace
Based Assessment.
PMID- 26414049
TI - In Reply to Ali.
PMID- 26414050
TI - Top or Flop: The Need to Improve Knowledge and Skills Achieved by Ultrasound
Medical Curricula.
PMID- 26414051
TI - Lifestyle Medicine Curricula: An Initiative to Include Lifestyle Medicine in Our
Nation's Medical Schools.
PMID- 26414052
TI - What's in a Name? The Necessary Transformation of the Academic Medical Center in
the Era of Population Health and Accountable Care.
AB - Academic medical centers (AMCs) and the physicians and other professionals who
lead them need to recognize they are in a business that is making a transition
from a system of "sickness" care to one of "health" care, accountable for the
health of defined populations and for the value (quality divided by cost) of the
services provided. This change has profound implications for how AMCs conceive
themselves, how they function, and how they are paid for the work that they do. A
failure to recognize how the disruption of the mission of AMCs is changing may
impair them as irrevocably as other changes caused the demise of Kodak, once the
world's leader in the manufacture and sale of photographic film and cameras.
Leaders of academic medicine need to understand, respond to, and ultimately lead
the transformation of our system of health. In this Commentary, the authors
review the pressures driving these changes and potential responses to them-a
process already under way. They summarize the issues in the question "Should the
words 'health' and 'system' take the place of 'medical' and 'center' in our
institutions' names and, more important, in how we conceive of what we do?" The
authors propose the name "academic health system" to better identify primary
objectives to measure success by the health of patients.
PMID- 26414053
TI - Why We Need to Build a Culture of Health in the United States.
AB - The United States spends $2.7 trillion a year on health care, more than any other
country by far, and yet the U.S. population is not healthy. In fact, the United
States loses $227 billion in productivity each year because of poor health. This
is not sustainable-and it is the reason behind the Robert Wood Johnson
Foundation's Culture of Health initiative. Culture of Health means so much more
than simply not being sick. It means embracing a definition of health as outlined
by the World Health Organization-a state of complete physical, mental, and social
well-being. And it means shifting the values-and the actions-in the United States
so that health becomes a part of everything we do. Health is the bedrock of
personal fulfillment. It is the backbone of prosperity and the key to creating a
strong and competitive nation. With health, children can grow up making the most
of life's opportunities. Businesses can rely on the vitality of workers to stay
competitive, and the military can perform at its highest level. But there is no
single way to cultivate health. This Commentary explores the principles behind
the Culture of Health initiative and examines the role of academic medicine in
achieving this vision. Different communities must come up with the approaches
that serve them best. Only by working toward a common goal in unique ways will a
true Culture of Health be attainable in the United States.
PMID- 26414055
TI - Artist's Statement: The Persistence of Clerkship Memory.
PMID- 26414054
TI - Sustaining the Clinical and Translational Research Workforce: Training and
Empowering the Next Generation of Investigators.
AB - There is mounting concern that clinician-scientists are a vanishing species and
that the pipeline for clinical and translational research (CTR) investigators is
in jeopardy. For the majority of current junior CTR investigators, the career
path involves first obtaining a National Institutes of Health (NIH)-funded K-type
career development award, particularly K08 and K23, and subsequently an NIH R01.
This transition, popularly referred to as K2R, is a major hurdle with a low
success rate and gaps in funding. In this Perspective, the authors identify
factors that facilitate K2R transition and important aspects of increasing and
sustaining the pipeline of CTR investigators. They also highlight significant
differences in success rates of women and those underrepresented in biomedical
research. Early career exposure to research methodology, protected time,
multidisciplinary mentoring, and institutional "culture shift" are important for
fostering and rewarding team science. Mentoring is the single most important
contributor to K2R success, and emerging evidence suggests that formal mentor
training and team mentoring are effective. Leadership training can empower junior
investigators to thrive as independent CTR investigators. Future research should
focus on delineating the difference between essential and supplemental factors to
achieve this transition, and mentoring methods that foster success, including
those that promote K2R transition of women and those underrepresented in
biomedical research. The Clinical and Translational Science Awards National
Consortium is well positioned to test existing models aimed at shortening the
time frame, increasing the rate of K2R transition, and identifying strategies
that improve success.
PMID- 26414056
TI - Commentary on Excerpts From Never Let Me Go.
PMID- 26414057
TI - A Night on Trauma.
PMID- 26414058
TI - Wise After the Fact.
PMID- 26414059
TI - A paper-based detection method of cancer cells using the photo-thermal effect of
nanocomposite.
AB - A novel paper-based dot immune-graphene-gold filtration assay (DIGGFA) for the
detection of breast cancer cells was developed based on the photo-thermal effect
of graphene oxide (GO)-Au nanocomposite. Anti-EpCAM antibody which specific to
the MCF-7 cell surface antigen, was immobilized on the nitrocellulose paper. The
GO-Au-anti-EpCAM composite would interact with the MCF-7 cells captured on the
nitrocellulose paper. After the test zone was irradiated by a laser, GO-Au
nanocomposite could generate heat, temperature contrast was recorded and positive
correlated with the cell number. Standard curve was prepared according to the
temperature contrast and the cell number. Under optimal conditions, this method
could detect a minimum of 600 MCF-7 cells with a near infrared laser and an
infrared temperature gun within 15 min. This simple and rapid method could be
applied to the clinical diagnosis in hospitals.
PMID- 26414060
TI - High-throughput method for the determination of residues of beta-lactam
antibiotics in bovine milk by LC-MS/MS.
AB - This study describes the development and validation procedures for scope
extension of a method for the determination of beta-lactam antibiotic residues
(ampicillin, amoxicillin, penicillin G, penicillin V, oxacillin, cloxacillin,
dicloxacillin, nafcillin, ceftiofur, cefquinome, cefoperazone, cephapirine,
cefalexin and cephalonium) in bovine milk. Sample preparation was performed by
liquid-liquid extraction (LLE) followed by two clean-up steps, including low
temperature purification (LTP) and a solid phase dispersion clean-up. Extracts
were analysed using a liquid chromatography-electrospray-tandem mass spectrometry
system (LC-ESI-MS/MS). Chromatographic separation was performed in a C18 column,
using methanol and water (both with 0.1% of formic acid) as mobile phase. Method
validation was performed according to the criteria of Commission Decision
2002/657/EC. Main validation parameters such as linearity, limit of detection,
decision limit (CCalpha), detection capability (CCbeta), accuracy, and
repeatability were determined and were shown to be adequate. The method was
applied to real samples (more than 250) and two milk samples had levels above
maximum residues limits (MRLs) for cloxacillin - CLX and cefapirin - CFAP.
PMID- 26414061
TI - [Robert Labauge (1922-2015)].
PMID- 26414062
TI - A New Approach to Evidence Synthesis in Traumatic Brain Injury: A Living
Systematic Review.
AB - Living systematic reviews (LSRs) are online summaries of health care research
that are updated as new research becomes available. This new development in
evidence synthesis is being trialled as part of the Collaborative European
NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI)
project. We will develop and sustain an international TBI knowledge community
that maintains up-to-date, high quality LSRs of the current state of knowledge in
the most important questions in TBI. Automatic search updates will be run three
monthly, and newly identified studies incorporated into the review. Review teams
will seek to publish journal updates at regular intervals, with abridged updates
available more frequently online. Future project stages include the integration
of LSR and other study findings into "living" clinical practice guidance. It is
hoped these efforts will go some way to bridging current temporal disconnects
between evidence, guidelines, and practice in TBI.
PMID- 26414063
TI - MIIB: A Metric to Identify Top Influential Bloggers in a Community.
AB - Social networking has revolutionized the use of conventional web and has
converted World Wide Web into the social web as users can generate their own
content. This change has been possible due to social web platforms like forums,
wikis, and blogs. Blogs are more commonly being used as a form of virtual
communication to express an opinion about an event, product or experience and can
reach a large audience. Users can influence others to buy a product, have certain
political or social views, etc. Therefore, identifying the most influential
bloggers has become very significant as this can help us in the fields of
commerce, advertisement and product knowledge searching. Existing approaches
consider some basic features, but lack to consider some other features like the
importance of the blog on which the post has been created. This paper presents a
new metric, MIIB (Metric for Identification of Influential Bloggers), based on
various features of bloggers' productivity and popularity. Productivity refers to
bloggers' blogging activity and popularity measures bloggers' influence in the
blogging community. The novel module of BlogRank depicts the importance of blog
sites where bloggers create their posts. The MIIB has been evaluated against the
standard model and existing metrics for finding the influential bloggers using
dataset from the real-world blogosphere. The obtained results confirm that the
MIIB is able to find the most influential bloggers in a more effective manner.
PMID- 26414066
TI - Kinetics of Ion Transport in Perovskite Active Layers and Its Implications for
Active Layer Stability.
AB - Solar cells fabricated using alkyl ammonium metal halides as light absorbers have
the right combination of high power conversion efficiency and ease of fabrication
to realize inexpensive but efficient thin film solar cells. However, they degrade
under prolonged exposure to sunlight. Herein, we show that this degradation is
quasi-reversible, and that it can be greatly lessened by simple modifications of
the solar cell operating conditions. We studied perovskite devices using
electrochemical impedance spectroscopy (EIS) with methylammonium (MA)-,
formamidinium (FA)-, and MA(x)FA(1-x) lead triiodide as active layers. From
variable temperature EIS studies, we found that the diffusion coefficient using
MA ions was greater than when using FA ions. Structural studies using powder X
ray diffraction (PXRD) show that for MAPbI3 a structural change and lattice
expansion occurs at device operating temperatures. On the basis of EIS and PXRD
studies, we postulate that in MAPbI3 the predominant mechanism of accelerated
device degradation under sunlight involves thermally activated fast ion transport
coupled with a lattice-expanding phase transition, both of which are facilitated
by absorption of the infrared component of the solar spectrum. Using these
findings, we show that the devices show greatly improved operation lifetimes and
stability under white-light emitting diodes, or under a solar simulator with an
infrared cutoff filter or with cooling.
PMID- 26414065
TI - Late Presentation into Care of HIV Disease and Its Associated Factors in Asia:
Results of TAHOD.
AB - Many HIV-infected individuals do not enter health care until late in the
infection course. Despite encouraging earlier testing, this situation has
continued for several years. We investigated the prevalence of late presenters
and factors associated with late presentation among HIV-infected patients in an
Asian regional cohort. This cohort study included HIV-infected patients with
their first positive HIV test during 2003-2012 and CD4 count and clinical status
data within 3 months of that test. Factors associated with late presentation into
care (CD4 count <200 cells/MUl or an AIDS-defining event within +/-3 months of
first positive HIV test) were analyzed in a random effects logistic regression
model. Among 3,744 patients, 2,681 (72%) were late presenters. In the
multivariable model, older patients were more likely to be late presenters than
younger (<=30 years) patients [31-40, 41-50, and >=51 years: odds ratio (OR) =
1.57, 95% confidence interval (CI) 1.31-1.88; OR = 2.01, 95% CI 1.58-2.56; and OR
= 1.69, 95% CI 1.23-2.31, respectively; all p <= 0.001]. Injecting drug users
(IDU) were more likely (OR = 2.15, 95% CI 1.42-3.27, p < 0.001) and those with
homosexual HIV exposure were less likely (OR = 0.45, 95% CI 0.35-0.58, p < 0.001)
to be late presenters compared to those with heterosexual HIV exposure. Females
were less likely to be late presenters (OR = 0.44, 95% CI 0.36-0.53, p < 0.001).
The year of first positive HIV test was not associated with late presentation.
Efforts to reduce the patients who first seek HIV care at the late stage are
needed. The identified risk factors associated with late presentation should be
utilized in formulating targeted public health intervention to improve earlier
entry into HIV care.
PMID- 26414067
TI - Evidence-Based Structural Model of the Staphylococcal Repressor Protein:
Separation of Functions into Different Domains.
AB - Horizontal transfer of mobile genetic elements within Staphylococci is of high
biomedical significance as such elements are frequently responsible for virulence
and toxic effects. Staphylococcus-encoded repressor proteins regulate the
replication of these mobile genetic elements that are located within the so
called pathogenicity islands. Here, we report structural and functional
characterization of one such repressor protein, namely the Stl protein encoded by
the pathogenicity island SaPIbov1. We create a 3D structural model and based on
this prediction, we investigate the different functionalities of truncated and
point mutant constructs. Results suggest that a helix-turn-helix motif governs
the interaction of the Stl protein with its cognate DNA site: point mutations
within this motif drastically decrease DNA-binding ability, whereas the
interaction with the Stl-binding partner protein dUTPase is unperturbed by these
point mutations. The 3D model also suggested the potential independent folding of
a carboxy-terminal domain. This suggestion was fully verified by independent
experiments revealing that the carboxy-terminal domain does not bind to DNA but
is still capable of binding to and inhibiting dUTPase. A general model is
proposed, which suggests that among the several structurally different repressor
superfamilies Stl-like Staphylococcal repressor proteins belong to the helix-turn
helix transcription factor group and the HTH motif is suggested to reside within
N-terminal segment.
PMID- 26414068
TI - Modelling cephalopod-inspired pulsed-jet locomotion for underwater soft robots.
AB - Cephalopods (i.e., octopuses and squids) are being looked upon as a source of
inspiration for the development of unmanned underwater vehicles. One kind of
cephalopod-inspired soft-bodied vehicle developed by the authors entails a
hollow, elastic shell capable of performing a routine of recursive ingestion and
expulsion of discrete slugs of fluids which enable the vehicle to propel itself
in water. The vehicle performances were found to depend largely on the elastic
response of the shell to the actuation cycle, thus motivating the development of
a coupled propulsion-elastodynamics model of such vehicles. The model is
developed and validated against a set of experimental results performed with the
existing cephalopod-inspired prototypes. A metric of the efficiency of the
propulsion routine which accounts for the elastic energy contribution during the
ingestion/expulsion phases of the actuation is formulated. Demonstration on the
use of this model to estimate the efficiency of the propulsion routine for
various pulsation frequencies and for different morphologies of the vehicles are
provided. This metric of efficiency, employed in association with the present
elastodynamics model, provides a useful tool for performing a priori energetic
analysis which encompass both the design specifications and the actuation pattern
of this new kind of underwater vehicle.
PMID- 26414069
TI - Traditional Cardiovascular Disease Risk Factor Management in Rheumatoid Arthritis
Compared to Matched Nonrheumatoid Arthritis in a US Managed Care Setting.
AB - OBJECTIVE: To compare traditional cardiovascular (CV) risk factor management
among patients with rheumatoid arthritis (RA) to that of matched non-RA controls
within a large US managed care setting. METHODS: Adult patients with RA and age-
and sex-matched general population (general controls) or osteoarthritis (OA)
controls were identified between January 1, 2007 and December 31, 2011. We
compared health care utilization, measurement, treatment, and treatment target
achievement of traditional CV risk factors among subgroups of CV comorbidity
during 1 year of followup between RA and controls. RESULTS: A total of 9,440 RA
patients, 31,009 general controls, and 10,352 OA controls were included. The
proportions with measurements (blood pressure [BP], low-density lipoprotein [LDL]
cholesterol, or hemoglobin A1c ), treatment (antihypertensive, statin, or anti
diabetes mellitus medications), and treatment target achievement were slightly
higher in patients with RA compared with general controls. Controlling for other
factors, RA patients were more likely to have a measurement of BP (odds ratio
[OR] 16.77 [95% confidence interval (95% CI) 10.01-28.08]) or LDL cholesterol (OR
1.25 [95% CI 1.13-1.39]), and to receive antihypertensive (OR 1.84 [95% CI 1.47
2.30]) or anti-diabetic medications (OR 1.26 [95% CI 1.01-1.56]) compared to
general controls. RA was not associated with receiving a statin (OR 1.01 [95% CI
0.92-1.12]); however, a target LDL level was more likely to be achieved in RA
compared to general controls (OR 1.27 [95% CI 1.17-1.37]) as well as target
levels of BP and hemoglobin A1c . These results were consistent with results for
OA controls except for a lower probability of receiving a statin in RA compared
to OA. CONCLUSION: Traditional CV risk factors in patients with RA were not less
aggressively managed compared to non-RA controls.
PMID- 26414070
TI - CXCR2 Inhibition Combined with Sorafenib Improved Antitumor and Antiangiogenic
Response in Preclinical Models of Ovarian Cancer.
AB - Antiangiogenic therapy is important for the treatment of gynecological cancer.
However, the therapeutic benefit derived from these treatments is transient,
predominantly due to the selective activation of compensatory proangiogenic
pathways that lead to rapid development of resistance. We aimed to identify and
target potential alternative signaling to anti-vascular endothelial growth factor
(VEGF) therapy, with a view toward developing a combination of antiangiogenic
agents to provide extended therapeutic benefits. We developed a preclinical in
vivo phenotypic resistance model of ovarian cancer resistant to antiangiogenic
therapy. We measured dynamic changes in secreted chemokines and angiogenic
signaling in tumors and plasma in response to anti-VEGF treatment, as tumors
advanced from the initial responsive phase to progressive disease. In tumors that
progressed following sorafenib treatment, gene and protein expression levels of
proangiogenic CXC chemokines and their receptors were significantly elevated,
compared with responsive tumors. The chemokine (C-X-C motif) ligand 8 (CXCL8),
also known as interleukin-8 (IL-8) increase was time-dependent and coincided with
the dynamics of tumor progression. We used SB225002, a pharmacological inhibitor
of chemokine (C-X-C motif) receptor 2 (CXCR2), to disrupt the CXC chemokine
mediated functions of ovarian cancer cells in in vitro assays of cell growth
inhibition, spheroid formation, and cell migration. The combination of CXCR2
inhibitor with sorafenib led to a synergistic inhibition of cell growth in vitro,
and further stabilized tumor progression following sorafenib in vivo. Our results
suggest that CXCR2-mediated chemokines may represent an important compensatory
pathway that promotes resistance to antiangiogenic therapy in ovarian cancer.
Thus, simultaneous blockage of this proangiogenic cytokine pathway using CXCR2
inhibitors and the VEGF receptor (VEGFR) pathway could improve the outcomes of
antiangiogenic therapy.
PMID- 26414072
TI - Prediction of Pulmonary Arterial Hypertension in Chronic Obstructive Lung Disease
from Three-Dimensional Vectorcardiographic Parameters.
AB - AIM: The objective of our study was to assess diagnostic value of three
dimensional (3D) vectorcardiographic (VCG) parameters in detecting pulmonary
arterial hypertension (PAH) in chronic obstructive lung disease (COLD) with and
without right ventricular hypertrophy (RVH). METHODS: The study group of 62
patients with COPD was stratified on the basis of color Doppler echocardiographic
findings into three subgroups: non-PAH (n = 23), PAH without RVH (n = 22), and
PAH with RVH (n = 17). Pairwise differences between the subgroups were evaluated
by one-way analysis of variance, and Pearson correlation analysis was used to
evaluate the significance of the correlations between pulmonary arterial systolic
pressure (PASP) and various VCG parameters. RESULTS: The azimuth of the QRS
vector decreased from -24 degrees in the non-PAH group to -62 degrees in PAH
without RVH and to -140 degrees in PAH with RVH (P < 0.01 for pairwise
differences between all three groups). Similar significant decrease was observed
for the azimuth of the ventricular gradient (VG) vector. Spatial QRS/T angle
increased from 69 degrees in the non-PAH group to 115 degrees in PAH without
RVH (P < 0.01). In the PAH group with RVH, QRS/T angle was 94 degrees (P < 0.05
for difference from the non-PAH group). There was a significant correlation
between PASP and QRS/T angle (r = 0.89, P < 0.05) and between PASP and the
azimuth of the VG vector (r = 0.86, P < 0.05). PASP increase from linear
regression model was 0.8 mmHg for a QRS/T angle increase by 10 degrees and 1.3
mmHg for each 10 degrees increase in the azimuth of the VG vector. CONCLUSION:
3DVCG parameters are potentially useful for predicting PASP in COLD patients, and
possibly also for differentiation between COLD patients with PAH and RVH from
those without RVH.
PMID- 26414071
TI - 2-Fluoro-L-Fucose Is a Metabolically Incorporated Inhibitor of Plant Cell Wall
Polysaccharide Fucosylation.
AB - The monosaccharide L-fucose (L-Fuc) is a common component of plant cell wall
polysaccharides and other plant glycans, including the hemicellulose xyloglucan,
pectic rhamnogalacturonan-I (RG-I) and rhamnogalacturonan-II (RG-II),
arabinogalactan proteins, and N-linked glycans. Mutations compromising the
biosynthesis of many plant cell wall polysaccharides are lethal, and as a result,
small molecule inhibitors of plant cell wall polysaccharide biosynthesis have
been developed because these molecules can be applied at defined concentrations
and developmental stages. In this study, we characterize novel small molecule
inhibitors of plant fucosylation. 2-fluoro-L-fucose (2F-Fuc) analogs caused
severe growth phenotypes when applied to Arabidopsis seedlings, including reduced
root growth and altered root morphology. These phenotypic defects were dependent
upon the L-Fuc salvage pathway enzyme L-Fucose Kinase/ GDP-L-Fucose
Pyrophosphorylase (FKGP), suggesting that 2F-Fuc is metabolically converted to
the sugar nucleotide GDP-2F-Fuc, which serves as the active inhibitory molecule.
The L-Fuc content of cell wall matrix polysaccharides was reduced in plants
treated with 2F-Fuc, suggesting that this molecule inhibits the incorporation of
L-Fuc into these polysaccharides. Additionally, phenotypic defects induced by 2F
Fuc treatment could be partially relieved by the exogenous application of boric
acid, suggesting that 2F-Fuc inhibits RG-II biosynthesis. Overall, the results
presented here suggest that 2F-Fuc is a metabolically incorporated inhibitor of
plant cellular fucosylation events, and potentially suggest that other 2
fluorinated monosaccharides could serve as useful chemical probes for the
inhibition of cell wall polysaccharide biosynthesis.
PMID- 26414074
TI - The influence of injection speed on pain during injection of local anaesthetic.
AB - STUDY OBJECTIVE: To determine the influence of injection speed on pain during
injection of local anaesthetics. METHODS: In a blinded randomised study with 36
healthy volunteers, each volunteer received three injections of 4.5 ml lidocaine
subcutaneously on the abdomen. The injections were given during 15 seconds (0.3
ml/s), 30 seconds (0.15 ml/s), and 45 seconds (0.1 ml/s). The needle tip remained
beneath the skin for 45 seconds during all three injections. Participants rated
the pain experienced on a 100 mm visual analogue scale (VAS) immediately after
each injection. After the last injection, they were asked which injections were
the least and most painful. RESULTS: The mean VAS pain score for the 15 seconds
injections was 26 (SD = 19), for the 30 seconds injections 24 (SD = 19), and for
the 45 seconds injections also 24 (SD = 18) (ns). Eight subjects preferred the 15
seconds injection, 15 preferred the 30 seconds injection, and 10 preferred the 45
seconds injection (ns). CONCLUSION: It is concluded that varying the injection
speed between 0.3 ml/s and 0.1 ml/s has no influence on the pain experienced
during subcutaneous injection of 4.5 ml lidocaine.
PMID- 26414073
TI - Genome Filtering for New DNA Biomarkers of Loa loa Infection Suitable for Loop
Mediated Isothermal Amplification.
AB - Loa loa infections have emerged as a serious public health problem in patients co
infected with Onchocerca volvulus or Wuchereria bancrofti because of severe
adverse neurological reactions after treatment with ivermectin. Accurate
diagnostic tests are needed for careful mapping in regions where mass drug
administration is underway. Loop-mediated isothermal amplification (LAMP) has
become a widely adopted screening method because of its operational simplicity,
rapidity and versatility of visual detection readout options. Here, we present a
multi-step bioinformatic pipeline to generate diagnostic candidates suitable for
LAMP and experimentally validate this approach using one of the identified
candidates to develop a species-specific LAMP assay for L. loa. The pipeline
identified ~140 new L. loa specific DNA repeat families as putative biomarkers of
infection. The consensus sequence of one family, repeat family 4 (RF4), was
compiled from ~ 350 sequences dispersed throughout the L. loa genome and maps to
a L. loa-specific region of the long terminal repeats found at the boundaries of
Bel/Pao retrotransposons. PCR and LAMP primer sets targeting RF4 specifically
amplified L. loa but not W. bancrofti, O. volvulus, Brugia malayi, human or
mosquito DNA. RF4 LAMP detects the DNA equivalent of one microfilaria (100 pg) in
25-30 minutes and as little as 0.060 pg of L. loa DNA (~1/1600th of a
microfilaria) purified from spiked blood samples in approximately 50 minutes. In
summary, we have successfully employed a bioinformatic approach to mine the L.
loa genome for species-specific repeat families that can serve as new DNA
biomarkers for LAMP. The RF4 LAMP assay shows promise as a field tool for the
implementation and management of mass drug administration programs and warrants
further testing on clinical samples as the next stage in development towards this
goal.
PMID- 26414076
TI - Fecal microbiota transplantation in gastrointestinal disease: 2015 update and the
road ahead.
AB - At its height, the Clostridium difficile infection epidemic caused approximately
7000 infections and 300 deaths per day in the USA. Fecal microbiota
transplantation (FMT) has demonstrated extraordinary clinical resolution, C.
difficile infection cure rates of over 90%, and low recurrence. In tandem with
the rise of FMT, the gastrointestinal microbiome has emerged as a 'vital' organ
armed with a wealth of microbe 'soldiers' more powerful than known antibiotics.
FMTs' reputation has diffused into many new 'indications' yet these appear to be
merely the tip of the iceberg when considering its potential applications. FMT as
a therapeutic tool has evolved from the original format of blended donor stool
and moved towards a refined product comprising a myriad of microbial components,
presented aesthetically as encapsulated lyophilized powder.
PMID- 26414079
TI - Systemic lupus erythematosus, bone health, and osteoporosis.
AB - PURPOSE OF REVIEW: This manuscript will provide a review of recent publications,
examining the correlation of systemic lupus erythematosus (SLE) with changes in
bone health and associated osteoporosis, highlighting prevalence, etiology,
diagnosis, and treatment. RECENT FINDINGS: Studies suggest that bone loss and
fractures are associated with SLE, related not only to the disease itself, but
also with low vitamin D and treatment side-effects. Understanding the mechanisms
of glucocorticoids on bone and the immunologic relationship of vitamin D, as well
as recognizing the role of chronic inflammation on bone, allows for better
understanding of skeletal side-effects. Further awareness of the association of
poor bone health has led to an increased need for prevention and treatment. New
imaging and treatment are emerging, although not recommended currently. SUMMARY:
Loss of bone density culminating in osteoporosis and fracture is a frequent
comorbidity in SLE patients at any age and is multifactorial in etiology.
Awareness and diagnosis is crucial because of its prevalence and morbidity.
Prevention is safe and effective in this high-risk population where diagnostic
measures and interventions are underutilized and guidelines are lacking.
PMID- 26414077
TI - Middle East respiratory syndrome: current status and future prospects for vaccine
development.
AB - The outbreaks of Middle East respiratory syndrome (MERS) previously in Middle
East and recently in South Korea have raised serious concerns worldwide,
reinforcing the importance of developing effective and safe vaccines against MERS
coronavirus (MERS-CoV). A number of vaccine candidates have been developed on the
basis of viral vectors, recombinant proteins, DNAs, nanoparticles, and
recombinant MERS-CoV, and some of them have shown efficacy in laboratory animals.
However, the paucity of financial support has made it difficult to transfer
effective candidates from the preclinical stage to clinical trials. Here, we
summarize currently available MERS vaccine candidates and illustrate strategies
for future development, with the aim of provoking government agencies and Big
Pharma to invest more funds for developing efficacious and safe MERS vaccines.
PMID- 26414080
TI - Vitamin D and anemia: insights into an emerging association.
AB - PURPOSE OF REVIEW: The current review highlights recent findings in the emerging
association between vitamin D and anemia through discussion of mechanistic
studies, epidemiologic studies, and clinical trials. RECENT FINDINGS: Vitamin D
has previously been found to be associated with anemia in various healthy and
diseased populations. Recent studies indicate that the association may differ
between race and ethnic groups and is likely specific to anemia of inflammation.
The mechanism underlying this association involves the reduction of
proinflammatory cytokines by vitamin D and the direct suppression of hepcidin
mRNA transcription. There is also evidence that vitamin D may be protective
against anemia by supporting erythropoiesis. Other calciotropic hormones
including fibroblast growth factor 23, and parathyroid hormone have also been
found to be associated with iron homeostasis and erythropoiesis. SUMMARY: Recent
advances in our understanding of the association between vitamin D and anemia
suggest that maintenance of sufficient vitamin D status may be important in
preventing anemia, particularly in diseases characterized by inflammation. Early
clinical trials have been promising, but further research is needed to define the
efficacy of vitamin D as a future approach for the treatment of anemia.
PMID- 26414081
TI - Bone loss in HIV: a contemporary review.
AB - PURPOSE OF REVIEW: Because of antiretroviral therapy (ART), people are living
with HIV infection longer than ever before. As this patient group ages, it is
expected that medical comorbidities such as osteoporosis and fragility fractures
will increase. The purpose of this review is to address the epidemiology and what
is known regarding the pathogenesis of bone loss in people living with HIV
infection with a focus on recently published literature. RECENT FINDINGS: HIV
infected individuals are at increased risk for low bone mineral density and bone
fractures. The cause of bone loss in HIV is multifactorial including traditional
risk factors some of which disproportionately affect HIV-infected individuals and
alterations in bone metabolism due to ART, HIV viral proteins and chronic
inflammation. Lifestyle modification, changing ART, calcium and vitamin D
supplementation and pharmacologic treatment for osteoporosis may all be employed
to abrogate bone loss in this patient group. SUMMARY: Clinicians should be aware
of the contributors to bone loss in people living with HIV in order to recognize
high-risk individuals and to take appropriate steps to address modifiable risk
factors to prevent future fracture.
PMID- 26414082
TI - Skeletal muscle and pediatric bone development.
AB - PURPOSE OF REVIEW: The purpose of this review is to summarize the recent clinical
findings surrounding the muscle-bone relationships in children, while considering
muscle adiposity, endocrine factors, and lifestyle influences (i.e., diet and
exercise) involved in pediatric musculoskeletal development. RECENT FINDINGS:
Positive relationships between cortical bone geometry and muscle mass, size and
function have been reported. Prospective studies in particular have helped
clarify some of the inconsistent relationships between muscle and cortical bone
volumetric density. Muscle fat is associated with impaired glucose handling and
muscular functionality, which may in turn have a downstream effect on cortical
bone growth during adolescence. Lifestyle factors such as healthful diets and
higher impact physical activities can promote optimal skeletal development by
improving the muscular phenotype and endocrine profile. SUMMARY: Muscle and bone
are two intricately-related tissue types; however, factors such as sex,
maturation, study design, and outcome measures studied can modify this
relationship. Further research is warranted to understand the impact of muscle
adiposity on cardiometabolic health, muscle function and, subsequently, pediatric
musculoskeletal development and fracture risk. Following age-specific diet and
physical activity recommendations should be a major focus in obtaining optimal
muscle and bone development throughout maturation.
PMID- 26414083
TI - Self-Healing Supramolecular Self-Assembled Hydrogels Based on Poly(L-glutamic
acid).
AB - Self-healing polymeric hydrogels have the capability to recover their structures
and functionalities upon injury, which are extremely attractive in emerging
biomedical applications. This research reports a new kind of self-healing
polypeptide hydrogels based on self-assembly between cholesterol (Chol)-modified
triblock poly(L-glutamic acid)-block-poly(ethylene glycol)-block-poly(L-glutamic
acid) ((PLGA-b-PEG-b-PLGA)-g-Chol) and beta-cyclodextrin (beta-CD)-modified
poly(L-glutamic acid) (PLGA-g-beta-CD). The hydrogel formation relied on the host
and guest linkage between beta-CD and Chol. This study demonstrates the
influences of polymer concentration and beta-CD/Chol molar ratio on viscoelastic
behavior of the hydrogels. The results showed that storage modulus was highest at
polymer concentration of 15% w/v and beta-CD/Chol molar ratio of 1:1. The effect
of the PLGA molecular weight in (PLGA-b-PEG-b-PLGA)-g-Chol on viscoelastic
behavior, mechanical properties and in vitro degradation of the supramolecular
hydrogels was also studied. The hydrogels showed outstanding self-healing
capability and good cytocompatibility. The multilayer structure was constructed
using hydrogels with self-healing ability. The developed hydrogels provide a
fascinating glimpse for the applications in tissue engineering.
PMID- 26414084
TI - Long-Term Function of Alginate-Encapsulated Islets.
AB - Human trials have demonstrated the feasibility of alginate-encapsulated islet
cells for the treatment of type 1 diabetes. Encapsulated islets can be protected
from the host's immune system and remain viable and functional following
transplantation. However, the long-term success of these therapies requires that
alginate microcapsules maintain their immunoprotective capacity and stability in
vivo for sustained periods. In part, as a consequence of different encapsulation
strategies, islet encapsulation studies have produced inconsistent results in
regard to graft functioning time, stability, and overall metabolic benefits.
Alginate composition (proportion of M- and G-blocks), alginate purity, the cross
linking ions (calcium or barium), and the presence or absence of additional
polymer coating layers influence the success of cell encapsulation. This review
summarizes the outcomes of long-term studies of alginate-encapsulated islet
transplants in animals and humans and provides a critical discussion of the graft
failure mechanisms, including issues with graft biocompatibility, transplantation
site, and integrity of the encapsulated islet grafts. Strategies to improve the
mechanical stability of alginate capsules and methods for monitoring graft
survival and function in vivo are presented.
PMID- 26414085
TI - The health benefits of reducing air pollution in Sydney, Australia.
AB - Among industrialised countries, fine particle (PM2.5) and ozone levels in the
Sydney metropolitan area of Australia are relatively low. Annual mean PM2.5
levels have historically remained below 8 MUg/m(3) while warm season (November
March) ozone levels occasionally exceed the Australian guideline value of 0.10
ppm (daily 1 h max). Yet, these levels are still below those seen in the United
States and Europe. This analysis focuses on two related questions: (1) what is
the public health burden associated with air pollution in Sydney; and (2) to what
extent would reducing air pollution reduce the number of hospital admissions,
premature deaths and number of years of life lost (YLL)? We addressed these
questions by applying a damage function approach to Sydney population, health,
PM2.5 and ozone data for 2007 within the BenMAP-CE software tool to estimate
health impacts and economic benefits. We found that 430 premature deaths (90% CI:
310-540) and 5800 YLL (95% CI: 3900-7600) are attributable to 2007 levels of
PM2.5 (about 2% of total deaths and 1.8% of YLL in 2007). We also estimate about
630 (95% CI: 410-840) respiratory and cardiovascular hospital admissions
attributable to 2007 PM2.5 and ozone exposures. Reducing air pollution levels by
even a small amount will yield a range of health benefits. Reducing 2007 PM2.5
exposure in Sydney by 10% would, over 10 years, result in about 650 (95% CI: 430
850) fewer premature deaths, a gain of 3500 (95% CI: 2300-4600) life-years and
about 700 (95% CI: 450-930) fewer respiratory and cardiovascular hospital visits.
These results suggest that substantial health benefits are attainable in Sydney
with even modest reductions in air pollution.
PMID- 26414086
TI - Direct Comparison of Wharton's Jelly and Bone Marrow-Derived Mesenchymal Stromal
Cells to Enhance Engraftment of Cord Blood CD34(+) Transplants.
AB - Cotransplantation of CD34(+) hematopoietic stem and progenitor cells (HSPCs) with
mesenchymal stromal cells (MSCs) enhances HSPC engraftment. For these
applications, MSCs are mostly obtained from bone marrow (BM). However, MSCs can
also be isolated from the Wharton's jelly (WJ) of the human umbilical cord. This
source, regarded to be a waste product, enables a relatively low-cost MSC
acquisition without any burden to the donor. In this study, we evaluated the
ability of WJ MSCs to enhance HSPC engraftment. First, we compared cultured human
WJ MSCs with human BM-derived MSCs (BM MSCs) for in vitro marker expression,
immunomodulatory capacity, and differentiation into three mesenchymal lineages.
Although we confirmed that WJ MSCs have a more restricted differentiation
capacity, both WJ MSCs and BM MSCs expressed similar levels of surface markers
and exhibited similar immune inhibitory capacities. Most importantly,
cotransplantation of either WJ MSCs or BM MSCs with CB CD34(+) cells into NOD
SCID mice showed similar enhanced recovery of human platelets and CD45(+) cells
in the peripheral blood and a 3-fold higher engraftment in the BM, blood, and
spleen 6 weeks after transplantation when compared to transplantation of CD34(+)
cells alone. Upon coincubation, both MSC sources increased the expression of
adhesion molecules on CD34(+) cells, although stromal cell-derived factor-1 (SDF
1)-induced migration of CD34(+) cells remained unaltered. Interestingly, there
was an increase in CFU-GEMM when CB CD34(+) cells were cultured on monolayers of
WJ MSCs in the presence of exogenous thrombopoietin, and an increase in BFU-E
when BM MSCs replaced WJ MSCs in such cultures. Our results suggest that WJ MSC
is likely to be a practical alternative for BM MSC to enhance CB CD34(+) cell
engraftment.
PMID- 26414087
TI - Societal costs of diabetes mellitus in Denmark.
AB - AIM: To provide comprehensive real-world evidence on societal diabetes
attributable costs in Denmark. METHODS: National register data are linked on an
individual level through unique central personal registration numbers in Denmark.
All patients in the Danish National Diabetes Register in 2011 (N = 318 729) were
included in this study. Complication status was defined according to data from
the Danish National Hospital Register. Diabetes-attributable costs were
calculated as the difference between costs of patients with diabetes and the
expected costs given the annual resource consumption of the diabetes-free
population. RESULTS: Societal costs attributable to diabetes were estimated to be
at least 4.27 billion EUR in 2011, corresponding to 14,349 EUR per patient-year.
A twofold higher healthcare resource usage was found for patients with diabetes
as compared with the diabetes-free population. Attributable costs, grouped
according to different components, were 732 million EUR for primary and secondary
care services, 153 million EUR for pharmaceutical drugs, 851 million EUR for
nursing services, 1.77 billion EUR in lost productivity and 761 million EUR for
additional costs. A steep increase in diabetes-attributable costs was found for
patients with major complications compared with patients without complications
across all cost components. For attributable healthcare costs this increase was
estimated to be 6,992 EUR per person-year after controlling for potential
confounders. CONCLUSIONS: Nearly half of the total costs of patients with
diabetes can be attributed directly to their diabetes. The majority of costs are
incurred among patients with major complications pointing to the importance of
secondary preventive efforts among patients with diabetes.
PMID- 26414088
TI - Halogenated quinolines discovered through reductive amination with potent
eradication activities against MRSA, MRSE and VRE biofilms.
AB - Small molecules capable of eradicating non-replicating bacterial biofilms are of
great importance to human health as conventional antibiotics are ineffective
against these surface-attached bacterial communities. Here, we report the
discovery of several halogenated quinolines (HQs) identified through a reductive
amination reaction that demonstrated potent eradication of MRSA (HQ-6; MBEC = 125
MUM), MRSE (HQ-3; MBEC = 3.0 MUM) and VRE (HQ-4, HQ-5 and HQ-6; MBEC = 1.0 MUM)
biofilms. HQs were evaluated using the Calgary Biofilm Device (CBD) and
demonstrated near equipotent killing activities against planktonic and biofilm
cells based on MBC and MBEC values. When tested against red blood cells, these HQ
analogues demonstrated low haemolytic activity (3 to 21% at 200 MUM) thus we
conclude that these HQ analogues do not operate primarily through the destruction
of bacterial membranes, typical of other biofilm-eradicating agents (i.e.,
antimicrobial peptides). HQ antibacterial agents are potent biofilm-eradicating
compounds and could lead to useful treatments for biofilm-associated bacterial
infections.
PMID- 26414089
TI - Group Visits to Improve Pediatric Attention-Deficit Hyperactivity Disorder
Chronic Care Management.
AB - OBJECTIVE: Children with attention-deficit hyperactivity disorder (ADHD) may
experience continued impairment at home and school even after medication
initiation. Group visits offer a way for pediatricians to provide more time to
address ongoing needs. A pilot study was undertaken to examine whether a group
visit model improved ADHD management in the pediatric medical home. METHODS:
Parents and children aged 6 to 18 years with ADHD were recruited and randomized
to group visits or a usual care control. Data included attendance at ADHD follow
up visits, parent-rated ADHD symptoms, adaptive functioning, and quality of life.
Longitudinal linear mixed models (continuous variables) and generalized linear
mixed models (binary outcomes) were used to compare groups. In our statistical
models, child and family were random effects; study assignment was a fixed
effect. RESULTS: Twenty families representing 29 children participated
(intervention: 9 parents/13 children and control: 11 parents/16 children). Aside
from race, baseline characteristics of participants were similar. None of the
intervention families missed the expected 5 ADHD follow-up visits over 1 year;
control families missed 1 or more visits over the same period. Intervention
families reported an improved level of adaptive functioning at 12 months compared
with control (mean severity score: 3.7 vs 4.4, p = .003). All families reported
greater limitations and poorer quality of life compared with national norms.
CONCLUSION: Group visits in the pediatric medical home can improve adherence, and
preliminary results show a variety of improvements for the family.
PMID- 26414090
TI - Examining Parents' Experiences and Information Needs Regarding Early
Identification of Developmental Delays: Qualitative Research to Inform a Public
Health Campaign.
AB - OBJECTIVE: The purpose of this study was to assess the approach and materials of
Centers for Disease Control and Prevention's "Learn the Signs. Act Early."
(LTSAE) health education campaign, which aims to improve awareness of
developmental milestones and early warning signs of developmental delay among
parents of young children. METHODS: We conducted 2 phases of qualitative
research. Focus groups assessed the campaign's objectives by exploring the
experiences of parents with children who have developmental delays or
disabilities to determine facilitators of and barriers to identification. In
depth interviews were conducted with parents of typically developing children,
who reviewed campaign materials and provided feedback on appropriateness, appeal,
and clarity with regard to the campaign's objectives. RESULTS: Phase 1: Parents
were typically the first to express concern about their child's development, and
most talked with their child's health care provider. Two categories of health
care providers emerged: those who proactively asked about a child's development,
used tools to facilitate conversations, and made referrals, and those who did not
ask about development, told parents to "wait and see," and did not provide
information about services and supports. Few parents knew about special education
services before identification. Phase 2: Participants found the campaign
materials appealing, but were unclear about how to act early and why acting early
was important. CONCLUSIONS: Results affirmed LTSAE's evidence-based approach to
educating parents about child development. Additional campaign considerations
include providing more information about how to act early and why acting early is
important and enhancing outreach to providers to help them communicate with
concerned parents.
PMID- 26414091
TI - Bringing Innovation to Attention-Deficit Hyperactivity Disorder Care.
PMID- 26414092
TI - Towards a Critical Reframing of Early Detection and Intervention for
Developmental Concerns.
PMID- 26414093
TI - Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain
Injury.
AB - This study examined the prevalence of growth hormone deficiency (GHD) in patients
with traumatic brain injury (TBI) during the post-acute phase of recovery and
whether GHD was associated with increased disability, decreased independence, and
depression. A secondary objective was to determine the accuracy of insulin-like
growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior
pituitary function was assessed in 235 adult patients with TBI through evaluation
of fasting morning hormone levels. GH levels were assessed through provocative
testing, specifically the glucagon stimulation test. GHD was diagnosed in a
significant number of patients, with 45% falling into the severe GHD (<=3 MUg/L)
category. IGF-1 levels were not predictive of GHD. Patients with GHD were more
disabled and less independent compared with those patients who were not GHD.
Those patients with more severe GHD also showed decreased levels of cortisol and
testosterone. Symptoms of depression were also more prevalent in this group. In
addition, patients with severe GHD had delayed admission to post-acute
rehabilitation. This study confirms the high prevalence of GHD in patients with
TBI and the necessity to monitor clinical symptoms and perform provocative
testing to definitively diagnose GHD.
PMID- 26414094
TI - Subjective acceleration of time experience in everyday life across adulthood.
AB - Most people believe that time seems to pass more quickly as they age. Building on
assumptions of socioemotional selectivity theory, we investigated whether
awareness that one's future lifetime is limited is associated with one's
experience of time during everyday activities across adulthood in 3 studies. In
the first 2 studies (Study 1: N = 608; Study 2: N = 398), participants completed
a web-based version of the day reconstruction method. In Study 3 (N = 392)
participants took part in a newly developed tomorrow construction method, a web
based experimental method for assessing everyday life plans. Results confirmed
that older adults' subjective interpretation of everyday episodes is that these
episodes pass more quickly compared with younger adults. The subjective
acceleration of time experience in old age was more pronounced during productive
activities than during regenerative-consumptive activities. The age differences
were partly related to limited time remaining in life. In addition, subjective
acceleration of time experience was associated with positive evaluations of
everyday activities. Findings suggest that subjective acceleration of time in
older adults' daily lives reflects an adaptation to limitations in time remaining
in life. (PsycINFO Database Record
PMID- 26414095
TI - Figuring out function: Children's and adults' use of ownership information in
judgments of artifact function.
AB - Across 3 experiments, we found evidence that information about who owns an
artifact influenced 5- to 10-year-old children's and adults' judgments about that
artifact's primary function. Children's and adults' use of ownership information
was underpinned by their inference that owners are typically familiar with owned
artifacts and are therefore likely to know their primary functions. Accordingly,
when this inference was undermined-when an artifact's owner was said to be
unfamiliar with the owned artifact-ownership was no longer used as a privileged
heuristic cue to artifact function. These experiments also revealed age-related
differences in how ownership information was prioritized relative to another well
studied source of information known to influence artifact cognition, namely,
information about an artifact's original designer-intended function.
Specifically, older children and adults were more likely than younger children to
prioritize design information over ownership information. Our results suggest
that children and adults differ in how they weight the relative importance of
these 2 sources of function-relevant information-likely reflecting age-related
changes in children's and adults' sensitivity to ownership and design information
across development. (PsycINFO Database Record
PMID- 26414096
TI - Longitudinal bidirectional relations between adolescents' sympathy and prosocial
behavior.
AB - Despite the importance of understanding sympathy and prosocial behaviors,
research on the development of these tendencies in adolescence remains relatively
sparse. In the present study, we examined age trends and bidirectional
longitudinal relations in sympathy and prosocial behaviors across early to middle
adolescents. Participants were 500 12-year-olds at Time 1 (52% girls, 70%
European American) who completed measures of sympathy and prosocial behaviors at
5 different time points, each approximately 1 year apart. Results showed
significant bidirectional relations between sympathy and prosocial behaviors
across all time points, and an initial decrease of prosocial behaviors followed
by an increase into middle adolescence. The implications for prosocial
developmental theories and research are discussed. (PsycINFO Database Record
PMID- 26414097
TI - Costs and benefits of children's physical and relational aggression trajectories
on peer rejection, acceptance, and friendships: Variations by aggression
subtypes, gender, and age.
AB - This study examined the associations between children's co-occurring relational
and physical aggression trajectories and their peer relations (i.e., peer
rejection, peer acceptance, and reciprocated friendships) from late childhood
(Grade 4; Mage = 10.0) to early adolescence (Grade 8; Mage = 13.9). Using a
sample of 477 children (240 girls), the findings indicated there were multiple
heterogeneous subgroups of children who followed distinct co-occurring aggression
trajectories. For each of these subgroups, multiple indices of their relational
development were assessed and findings revealed notable group differences. These
results have implications about the potential costs and benefits of aggression,
and how its associations with children's peer relationships may vary as a
function of aggression subtype, developmental timing, and gender.
PMID- 26414098
TI - Increased expression of E3 ubiquitin ligases targeting p53 in CLL patients with
wild-type TP53 exhibits associations with clinical features of the disease.
PMID- 26414099
TI - Bond-Selective and Mode-Specific Dissociation of CH3D and CH2D2 on Pt(111).
AB - Infrared laser excitation of partially deuterated methanes (CH3D and CH2D2) in a
molecular beam is used to control their dissociative chemisorption on a Pt(111)
single crystal and to determine the quantum state-resolved dissociation
probabilities. The exclusive detection of C-H cleavage products adsorbed on the
Pt(111) surface by infrared absorption reflection spectroscopy indicates strong
bond selectivity for both methane isotopologues upon C-H stretch excitation.
Furthermore, the dissociative chemisorption of both methane isotopologues is
observed to be mode-specific. Excitation of symmetric C-H stretch modes produces
a stronger reactivity increase than excitation of the antisymmetric C-H stretch
modes, whereas bend overtone excitation has a weaker effect on reactivity. The
observed mode specificity and bond selectivity are rationalized by the sudden
vector projection model in terms of the overlap of the reactant's normal mode
vectors with the reaction coordinate at the transition state.
PMID- 26414100
TI - Hepatitis B virus surface antibody titers in babies administered hepatitis B
immune globulin both intravenously and intramuscularly after birth.
AB - OBJECTIVE: High rates of vertical transmission of hepatitis B virus (HBV)
infection from carrier mothers to their babies are observed in hepatitis B e
antigen (HBeAg)-positive mothers under the existing protocol. The current status
suggests that the existing protocol may be insufficient for the prevention of
mother-to-child transmission (MTCT) in HBeAg-positive mothers. To achieve
complete prevention of HBV vertical transmission, we designed a protocol
implementing intravenous administration along with ordinary intramuscular
administration of HBV immune globulin (HBIG) to the baby after birth. METHODS: We
compared the HBV surface antibody (HBsAb) titer in babies who were simultaneously
administered HBIG both intravenously and intramuscularly after birth with that in
babies who received HBIG only intramuscularly. RESULTS: The HBsAb titer rose
rapidly after administration in the combined administration group, and the
elevated titer was maintained for approximately 2 months. Although the antibody
titer at the peak was nearly 6 times greater in the combined administration group
than in the intramuscular administration group, the combined administration of
HBIG did not have any effect on total IgG antibody levels in the bloodstream.
CONCLUSION: The combined protocol was demonstrated to be safe and superior to the
protocol of only intramuscular HBIG administration with respect to rapid
elevation of HBsAb in the bloodstream. It could be an effective method for the
prevention of MTCT in HBeAg-positive mothers.
PMID- 26414101
TI - Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli.
AB - Kidney transplantation is often the most effective therapy for end-stage renal
disease, but there are not enough donor organs to meet the rising demand. Tissue
engineering of kidneys is a potential solution to this organ shortage. Achieving
microvascular perfusion has been a major barrier to engineering tissues beyond
thin muscularized sheets such as the bladder wall. Our laboratory has previously
reported that human umbilical vein endothelial cells (ECs) transduced with the
antiapoptotic protein Bcl-2 will spontaneously organize into perfused
microvessels within type I collagen gels when implanted in immunodeficient mice.
To test if this system can be used to perfuse more complex structures, we
combined Bcl-2-transduced ECs (Bcl-2-ECs) with renal glomeruli, the specialized
vascular filtration units of the kidney. Microdissected green fluorescent protein
expressing rat glomeruli suspended in type I collagen gels were implanted within
immunodeficient mice with or without the inclusion of Bcl-2-ECs. Survival of rat
glomeruli was enhanced by coimplantation with Bcl-2-ECs. Intravital rhodamine
dextran injections demonstrated that surviving glomeruli were perfused through
Bcl-2-EC-derived microvessels. Perfused glomeruli maintained podocin staining,
but transmission electron microscopy revealed endothelial swelling and podocyte
foot process effacement. Anastomosis of microvessels derived from Bcl-2-ECs with
glomerular capillaries provides proof of concept that self-assembled microvessels
can perfuse specialized organ structures such as glomeruli, but that perfusion
alone may be insufficient to maintain normal structure.
PMID- 26414102
TI - Lyme borreliosis: reviewing potential vaccines, clinical aspects and health
economics.
AB - Lyme borreliosis (LB) is a multisystem infectious disease with a growing burden
in many parts of North America, Asia and Europe. Persistent infection of LB can
usually be treated effectively with antibiotic therapy, but it may be followed by
post-treatment Lyme disease syndrome. Therefore, it is important to begin with
treatment in the early phase of the disease. Vaccination shows potential as the
most effective way of preventing LB and reducing its burden in these continents.
It is concluded that there is a need for continuous effort in research from all
perspectives on LB, especially regarding prevention with novel vaccines, their
development, clinical efficacy and cost-effectiveness. This review may help to
further develop (cost-) effective strategies for prevention and control of the
disease to reduce its burden and achieve population-wide health benefits.
PMID- 26414103
TI - Hemispheric specialization of impaired disengagement of attention in depression:
a tachistoscopic method.
AB - Difficulty shifting attention away from negative stimuli once engaged is a well
established cognitive bias observed in depression. This study attempted to
determine whether this impaired disengagement of attention is lateralized in the
brain. Thirty depressed and 30 control participants performed an attention
disengagement task wherein the valence of the stimulus and the visual field was
presented. The depressed group had longer reaction times than the control group,
indicative of the typical cognitive and psychomotor slowing seen in depression.
The effect of visual field presentation on the ability to disengage attention
however was different for controls as compared to the patients. In controls, a
distinct right hemisphere advantage was seen for disengaging attention which is
in line with research that has identified right hemisphere structures as the seat
of behavioural inhibition. In the depressed group, however, this right hemisphere
advantage was not observed.
PMID- 26414104
TI - Controlled Directional Crystallization of Oligothiophenes Using Zone Annealing of
Preseeded Thin Films.
AB - We demonstrate a simple route to directionally grow crystals of oligothiophenes,
based on 2,5-bis(3-alkylthiophen-2-yl)thieno[3,2-b]thiophene with degrees of
polymerization of 2 (BTTT-2) and 4 (BTTT-4) via zone annealing (ZA) of preseeded
films. ZA of spun-cast films of BTTT-2 does not yield highly aligned crystals.
However, if the film is oven-annealed briefly prior to ZA, highly aligned
crystals that are millimeters in length can be grown, whose length depends on the
velocity of the ZA front. The precrystallized region provides existing nuclei
that promote crystal growth and limit nucleation of new crystals in the melted
region. Aligned crystals of BTTT-2 can be obtained even when the moving velocity
for ZA is an order of magnitude greater than the crystal growth rate. The
relative nucleation rate to the crystallization rate for BTTT-4 is greater than
that for BTTT-2, which decreases the length over which BTTT-4 can be aligned to
~500 MUm for the conditions examined. The temperature gradient and moving
velocity of ZA enable control of the length of the aligned crystalline structure
at the macroscale.
PMID- 26414105
TI - Antimicrobial use in swine production and its effect on the swine gut microbiota
and antimicrobial resistance.
AB - Antimicrobials have been used in swine production at subtherapeutic levels since
the early 1950s to increase feed efficiency and promote growth. In North America,
a number of antimicrobials are available for use in swine. However, the
continuous administration of subtherapeutic, low concentrations of antimicrobials
to pigs also provides selective pressure for antimicrobial-resistant bacteria and
resistance determinants. For this reason, subtherapeutic antimicrobial use in
livestock remains a source of controversy and concern. The swine gut microbiota
demonstrates a number of changes in response to antimicrobial administration
depending on the dosage, duration of treatment, age of the pigs, and gut location
that is sampled. Both culture-independent and -dependent studies have also shown
that the swine gut microbiota contains a large number of antimicrobial resistance
determinants even in the absence of antimicrobial exposure. Heavy metals, such as
zinc and copper, which are often added at relatively high doses to swine feed,
may also play a role in maintaining antimicrobial resistance and in the stability
of the swine gut microbiota. This review focuses on the use of antimicrobials in
swine production, with an emphasis on the North American regulatory context, and
their effect on the swine gut microbiota and on antimicrobial resistance
determinants in the gut microbiota.
PMID- 26414106
TI - Chemical Vapor Deposition of Large-Sized Hexagonal WSe2 Crystals on Dielectric
Substrates.
AB - High-quality large-sized hexagoal WSe2 crystals can be grown on dielectric
substrates using atmospheric chemical vapor deposition in the presence of
hydrogen gas. These hexagonal crystals (lateral width >160 um) have a carrier
mobility of 100 cm(2) V(-1) s(-1) and a photoresponsivity of ~1100 mA W(-1),
which is comparable to that of exfoliated flakes.
PMID- 26414108
TI - Low-dose adjunctive cilostazol in patients with complex lesions undergoing
percutaneous coronary intervention.
AB - Patients with complex coronary lesions undergoing percutaneous coronary
intervention (PCI) have more major adverse cardiac events (MACE) than do those
with simpler cases. Therefore, intensive antiplatelet therapy might be needed in
these patients. A total of 127 patients with complex lesions undergoing PCI in
the Second Hospital of Tianjin Medical University from October 2012 to April 2014
were randomized to receive either dual (aspirin plus clopidogrel, DAPT, n = 66),
or triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol; TAPT, n
= 61). Patients in the TAPT group received low-dose cilostazol (100 mg loading,
followed with 50 mg twice per day) for 3-6 months. The primary endpoint was
composite MACE. The complex coronary target lesions were defined as at least one
of the following: left main disease; severe 3-vessel disease; chronic total
occlusion lesions; true bifurcation lesion; ostial lesions; severe calcified
lesions; and highly thrombotic lesions. The two groups had similar baseline
clinical and angiographic characteristics. One-year clinical outcomes showed that
the TAPT group had significantly lower incidences of myocardial infarction (1.6%
vs 13.6%, P = 0.018) and MACE (1.6% vs 16.7%, P = 0.004) than DAPT group. The
DAPT group had two cases of stent thrombosis, while the TAPT group did not.
Furthermore, adjunctive low-dose cilostazol didn't significantly increase the
incidence of bleeding events (26.2% vs 19.7%, P = 0.381) regardless of major
(4.9% vs 4.5%, P = 0.921) or minor (21.3% vs 15.2%, P = 0.368) bleeding events.
In conclusion, low-dose adjunctive cilostazol seems superior to dual antiplatelet
therapy in reducing recurrent ischemic events in patients with complex coronary
lesions and the two test groups have a similar incidence of bleeding events.
PMID- 26414107
TI - Prognostic value of pretherapy platelet elevation in oropharyngeal cancer
patients treated with chemoradiation.
AB - The purpose of this study is to evaluate potential associations between increased
platelets and oncologic outcomes in oropharyngeal cancer patients receiving
concurrent chemoradiation. A total of 433 oropharyngeal cancer patients (OPC)
treated with intensity-modulated radiation therapy (IMRT) with concurrent
chemotherapy between 2002 and 2012 were included under an approved IRB protocol.
Complete blood count (CBC) data were extracted. Platelet and hemoglobin from the
last phlebotomy (PLTpre-chemoRT, Hgbpre-chemoRT ) before start of treatment were
identified. Patients were risk-stratified using Dahlstrom-Sturgis criteria and
were tested for association with survival and disease-control outcomes.
Locoregional control (LRC), freedom from distant metastasis (FDM) and overall
survival (OS) were decreased (p < 0.03, p < 0.04 and p < 0.0001, respectively)
for patients with PLTpre-chemoRT value of >=350 * 10(9) /L. Actuarial 5-year
locoregional control (LRC) and FDM were 83 and 85% for non-thrombocythemic
patients while patient with high platelets had 5-year LRC and FDM of 73 and 74%,
respectively. Likewise, 5-year OS was better for patients with normal platelet
counts by comparison (76 vs. 57%; p < 0.0001). Comparison of univariate
parametric models demonstrated that PLTpre-chemoRT was better among tested
models. Multivariate assessment demonstrated improved performance of models which
included pretherapy platelet indices. On Bayesian information criteria analysis,
the optimal prognostic model was then used to develop nomograms predicting 3-, 5-
and 10-year OS. In conclusion, pretreatment platelet elevation is a promising
predictor of prognosis, and further work should be done to elucidate the utility
of antiplatelets in modifying risk in OPC patients.
PMID- 26414110
TI - Insulin Dependence Increases the Risk of Failure After Total Knee Arthroplasty in
Morbidly Obese Patients.
AB - The aims of this study were to compare the outcomes between nondiabetic (n=1284),
type II diabetic (n=530), and insulin-dependent type II diabetic (n=164) morbidly
obese (body mass index >=40 kg/m(2)) patients undergoing primary total knee
arthroplasty at 6-year follow-up. Patients with type II diabetes mellitus (DM)
had similar outcomes when compared with non-DM patients. However, patients with
insulin dependence had an increased risk of reoperation (hazard ratio [HR], 1.8;
P=.005), revision (HR, 2; P=.02), and periprosthetic joint infection (HR, 2.1;
P=.03), as well as decreased 10-year implant survivorship (84% vs 92%; P=.01)
when compared to non-DM patients. Prospective studies should further evaluate
outcomes and optimization measures within this population. LEVEL OF EVIDENCE:
Level III-prognostic study.
PMID- 26414109
TI - Thyroid Dysfunction in Patients with Metastatic Carcinoma Treated with Sunitinib:
Is Thyroid Autoimmunity Involved?
AB - BACKGROUND: Sunitinib is a tyrosine kinase inhibitor (TKI) inducing thyroid
dysfunction, but the precise mechanism(s) involved remains to be explained,
including the role of thyroid autoimmunity. The objective of this study was to
evaluate thyroid function, parameters of autoimmunity, and thyroid ultrasound
findings in patients with metastatic cancer and normal thyroid
function/autoimmunity before the initiation of sunitinib therapy. This was a
prospective, observational cohort study. METHODS: Twenty-seven patients with
metastatic carcinomas at comparable tumor stages were evaluated over 12-18 months
after initiating therapy with sunitinib given at a daily oral dose of 50 mg for
four weeks (ON), followed by one to two weeks off therapy (OFF). Serum
thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and
antithyroglobulin (TgAb), and antithyroid peroxidase (TPOAb) autoantibodies were
measured in all cases. Thyroid morphology and volume were evaluated by echo-color
Doppler ultrasound. RESULTS: A total of 16/27 patients (60%) became hypothyroid
(TSH range 7-114 mIU/L) within 30-120 days of therapy. The thyroid volume
decreased in 24/27 (89%) patients (from M = 14.6 mL, SD = 6.4 mL to M = 3.8 mL,
SD = 2.6 mL after 12 months; p < 0.001), together with the appearance of mild to
severe hypoechogenicity. TPOAb (40-3000 IU/mL) became detectable in 7/27 (25%)
patients, and TPOAb-positive patients displayed a higher degree of hypothyroidism
and volume reduction. The progression-free survival (PFS) was significantly
longer in patients developing TPOAb (10.8 months) than in the other group of
patients (5.8 months). CONCLUSIONS: These data confirm the thyroid inhibitory
effect of sunitinib, in keeping with the key role of kinases in controlling
thyroid function and growth. However, the novel appearance of TPOAb in a subgroup
of patients with more severe hypothyroidism and longer survival indicates that
sunitinib may also trigger/exacerbate thyroid autoimmunity contributing to
thyroid failure. The development of TPOAb was associated with a longer PFS.
PMID- 26414111
TI - The AMPK enzyme-complex: from the regulation of cellular energy homeostasis to a
possible new molecular target in the management of chronic inflammatory
disorders.
AB - INTRODUCTION: Adenosine monophosphate-activated protein kinase (AMPK), known as
an enzymatic complex that regulates the energetic metabolism, is emerging as a
pivotal enzyme and enzymatic pathway involved in the regulation of immune
homeostatic networks. It is also involved in the molecular mechanisms underlying
the pathophysiology of chronic inflammatory diseases. AREAS COVERED: AMPK is
expressed in several immune cell types including macrophages, lymphocytes,
neutrophils and dendritic cells, and governs a broad array of cell functions,
which include cytokine production, chemotaxis, cytotoxicity, apoptosis and
proliferation. Based on its wide variety of immunoregulatory actions, the AMPK
system has been targeted to reveal its impact on the course of immune-related
diseases, such as atherosclerosis, psoriasis, joint inflammation and inflammatory
bowel diseases. EXPERT OPINION: The identification of AMPK subunits responsible
for specific anti-inflammatory actions and the understanding of the underlying
molecular mechanisms will promote the generation of novel AMPK activators,
endowed with improved pharmacodynamic and pharmacokinetic profiles. These new
tools will aid us to utilize AMPK pathway activation in the management of acute
and chronic inflammatory diseases, while minimizing potential adverse reactions
related to the effects of AMPK on metabolic energy.
PMID- 26414112
TI - The Effect of Renal Cysts on the Fragmentation of Renal Stones During Shockwave
Lithotripsy: A Comparative In Vitro Study.
AB - PURPOSE: To assess the potential effect of simple renal cysts (SRC) on stone
fragmentation during shockwave lithotripsy (SWL) in an in vitro model. MATERIALS
AND METHODS: The in vitro model was constructed using 10% ordnance gelatin (OG).
Models were created to mimic four scenarios: Model A-with an air-filled cavity
(suboptimal for stone fragmentation); model B-without a cavity (normal anatomy);
model C-with a 3-cm serum filled cavity (to represent a small SRC); model D-with
a 4-cm serum filled cavity (to represent a larger SRC). SWL was applied to 24
standardized phantom stones (weight of 2+/-0.1 g) in each model using a
standardized protocol. Stone fragments were retrieved, then dried overnight at
room air temperature. Fragmentation coefficient (FC) was calculated for each
stone, for fragments<4 mm and <2 mm. RESULTS: The OG in vitro model was robust
enough for the proposed research. There was no fragmentation evident in model A
as expected. The mean FC was 29.7 (+/-20.5) and 39.7 (+/-23.7) for <4 mm
fragments (P=0.069) and 7.6 (+/-4.1) and 10.6 (+/-6.7) for <2 mm fragments
(P=0.047), for noncystic and cystic models, respectively. The mean FC was 29.7
(+/-20.5), 38.8 (+/-26.2) and 40.7 (+/-21.3) for <4 mm fragments (P=0.213) and
7.6 (+/-4.1), 11.1 (+/-8) and 10.2 (+/-5.3) for <2 mm fragments (P=0.138), for
models B, C, and D, respectively. CONCLUSION: Our in vitro experiment confirms
better stone fragmentation associated with SWL in the presence of adjacent SRC.
PMID- 26414113
TI - Dissociating associative and motor aspects of action understanding: Processing of
dual-ended tools by 16-month-old infants.
AB - When learning about the functions of novel tools, it is possible that infants may
use associative and motoric processes. This study investigated the ability of 16
month-olds to associate the orientation in which an actor held a dual-function
tool with the actor's prior demonstrated interest in one of two target objects,
and their use of the tool on that target. The actors' hand posture did not differ
between conditions. The infants were shown stimuli in which two actors acted upon
novel objects with a novel tool, each actor employing a different function of the
tool. Using an eye-tracker, infants' looking time at images depicting the actors
holding the tool in an orientation congruent or incongruent with the actor's goal
was measured. Infants preferred to look at the specific part of the tool that was
incongruent with the actor's goal. Results show that the association formed
involves the specific part of the tool, the actor, and the object the actor acted
upon, but not the orientation of the tool. The capacity to form such associations
is demonstrated in this study in the absence of motor information that would
allow 16-month-olds to generate a specific representation of how the tool should
be held for each action via mirroring processes.
PMID- 26414114
TI - Addition of Amino Acids to Further Stabilize Lyophilized Sucrose-Based Protein
Formulations: I. Screening of 15 Amino Acids in Two Model Proteins.
AB - In small amounts, the low molecular weight excipients-sorbitol and glycerol-have
been shown to stabilize lyophilized sucrose-based protein formulations. The
purpose of this study was to explore the use of amino acids as low molecular
weight excipients to similarly enhance stability. Model proteins, recombinant
human serum albumin and alpha-chymotrypsin, were formulated with sucrose in
combination with one of 15 amino acid additives. Each formulation was lyophilized
at 1:1:0.3 (w/w) protein-sucrose-amino acid. Percent total soluble aggregate was
measured by size-exclusion chromatography before and after storage at 50 degrees
C for 2 months. Classical thought might suggest that the addition of the amino
acids to the sucrose-protein formulations would be destabilizing because of a
decrease in the system's glass transition temperature. However, significant
improvement in storage stability was observed for almost all formulations at the
ratio of amino acid used. Weak correlations were found between the extent of
stabilization and both amino acid molar volume and side-chain charge. The
addition of amino acids at a modest level generally improves storage stability,
often by more than a 50% increase, for lyophilized sucrose-based protein
formulations.
PMID- 26414115
TI - Asymptomatic Versus Symptomatic Ankle Joints in Rheumatoid Arthritis: A High
Resolution B-Mode and Power Doppler Ultrasound Study.
AB - OBJECTIVE: Ankle joints are frequently neglected in activity scoring systems,
including the Disease Activity Score in 28 joints (DAS28). Only a few studies
have assessed pathologies detected by ultrasonography of the ankles in
symptomatic rheumatoid arthritis (RA) patients. We evaluated ankle joints in RA
patients regardless of symptomatology, using musculoskeletal ultrasound (MSUS) as
well as power Doppler ultrasound (PDUS). METHODS: A total of 160 ankle joints of
80 RA patients were examined using MSUS and PDUS, according to the European
League Against Rheumatism MSUS guidelines. Additionally, the talonavicular joints
(TNJs) and the medial and the lateral tendon compartments were examined. The
visual analog scale (VAS) score was recorded for each patient. RESULTS: A total
of 80 RA patients with a median age of 60 years and disease duration of 5 years
were enrolled in our study. The median DAS28 score was 5. A total of 97 ankles
were painful (VAS 1-10), whereas 63 ankles were asymptomatic (VAS 0). Overall,
the predominant pathology was arthritis of the tibiotalar joint (TTJ) and/or TNJ
in 124 ankles (77%), followed by tenosynovitis of the medial compartment tendons
in 44 ankles (28%). Arthritis of the TTJ was present in 59% and synovitis of the
TNJ in 35% of the symptomatic ankles. In asymptomatic ankles, TTJ synovitis was
detected in 35%, whereas TNJ arthritis was observed in 18%. PDUS activity was
higher in the subgroup of symptomatic ankles. CONCLUSION: The most frequent
pathologies detected by MSUS were arthritis of the TTJ and TNJ, followed by
tenosynovitis of the medial compartment tendons. Pathologic findings were more
frequent in symptomatic but also common in asymptomatic patients, whereas PDUS
activity was generally low and mainly observed in symptomatic patients.
PMID- 26414116
TI - Interplay of Promoter Usage and Intragenic CpG Content: Impact on GFP Reporter
Gene Expression.
AB - Successful therapeutic protein production in vitro and in vivo requires efficient
and long-term transgene expression supported by optimized vector and transgene
cis-regulatory sequence elements. This study provides a comparative analysis of
CpG-rich, highly expressed, versus CpG-depleted, poorly expressed green
fluorescent protein (GFP) reporter transgenes, transcribed by various promoters
in two different cell systems. Long-term GFP expression from a defined locus in
stable Chinese hamster ovary cells was clearly influenced by the combination of
transgene CpG content and promoter usage, as shown by differential silencing
effects on selection pressure removal among the cytomegalovirus (CMV) promoter
and elongation factor (EF)-1alpha promoter. Whereas a high intragenic CpG content
promoted local DNA methylation, CpG depletion rather accelerated transgene loss
and increased the local chromatin density. On lentiviral transfer of various
expression modules into epigenetically sensitive P19 embryonic pluripotent
carcinoma cells, CMV promoter usage led to rapid gene silencing irrespective of
the intragenic CpG content. In contrast, EF-1alpha promoter-controlled constructs
showed delayed silencing activity and high-level transgene expression, in
particular when the CpG-rich GFP reporter was used. Notably, GFP silencing in P19
cells could be prevented completely by the bidirectional, dual divergently
transcribed A2UCOE (ubiquitously acting chromatin-opening element derived from
the human HNRPA2B1-CBX3 locus) promoter. Because the level of GFP expression by
the A2UCOE promoter was entirely unaffected by the intragenic CpG level, we
suggest that A2UCOE can overcome chromatin compaction resulting from intragenic
CpG depletion due to its ascribed chromatin-opening abilities. Our analyses
provide insights into the interplay of the intragenic CpG content with promoter
sequences and regulatory sequence elements, thus contributing toward the design
of therapeutic transgene expression cassettes for future gene therapy
applications.
PMID- 26414117
TI - Phenotypic plasticity and targeting of Siglec-F(high) CD11c(low) eosinophils to
the airway in a murine model of asthma.
AB - Eosinophil recruitment in asthma is a multistep process, involving both trans
endothelial migration to the lung interstitium and trans-epithelial migration
into the airways. While the trans-endothelial step is well studied, trans
epithelial recruitment is less understood. To contrast eosinophil recruitment
between these two compartments, we employed a murine kinetics model of asthma.
Eosinophils were phenotyped by multicolor flow cytometry in digested lung tissue
and bronchoalveolar lavage (BAL) simultaneously, 6 h after each ovalbumin (OVA)
challenge. There was an early expansion of tissue eosinophils after OVA challenge
followed by eosinophil buildup in both compartments and a shift in phenotype over
the course of the asthma model. Gradual transition from a Siglec-F(med) CD11c(-)
to a Siglec-F(high) CD11c(low) phenotype in lung tissue was associated with
eosinophil recruitment to the airways, as all BAL eosinophils were of the latter
phenotype. Secondary microarray analysis of tissue-activated eosinophils
demonstrated upregulation of specific integrin and chemokine receptor signature
suggesting interaction with the mucosa. Using adhesion assays, we demonstrated
that integrin CD11c mediated adhesion of eosinophils to fibrinogen, a significant
component of epithelial barrier repair and remodeling. To the best of our
knowledge, this is the only report to date dissecting compartmentalization of
eosinophil recruitment as it unfolds during allergic inflammation. By capturing
the kinetics of eosinophil phenotypic change in both tissue and BAL using flow
cytometry and sorting, we were able to demonstrate a previously undocumented
association between phenotypic shift of tissue-recruited eosinophils and their
trans-epithelial movement, which implicates the existence of a specific mechanism
targeting these cells to mucosal airways.
PMID- 26414119
TI - A combination of retinal morphology and visual electrophysiology testing
increases diagnostic yield in Parkinson's disease.
AB - BACKGROUND: Impaired vision and remodeled foveal pit have been demonstrated in
Parkinson's disease (PD) patients using different techniques. METHODS: Ten PD (20
eyes) and eight healthy controls (HC) subjects (16 eyes) were enrolled. Subjects
were evaluated for N70 and P100 latencies using two-channel VEP with pattern
reversal and on/off pattern; Contrast sensitivity (CS) using Pelli-Robson chart;
macular thickness measured using Zeiss-HD optical coherence tomography (OCT).
RESULTS: PD patients had a significantly delayed N70 (reversal pattern) and P100
(on/off pattern), lower CS score, and decreased retinal thickness at temporal 1.5
2.5 mm from the foveola. N70 latency was negatively correlated with CS (R =
0.419, P = 0.01) and average GCL-IPL thickness (R = -0.529, P = 0.001). CS was
positively correlated with parafoveal thickness (R = 0.490, P = 0.002). A
combination of parafoveal thickness and CS score yielded an AUC of 0.784 for PD
discrimination which increased to 0.844 when combined with N70 and P100 measures.
CONCLUSION: A combination of pattern reversal VEP latency, CS score, and inner
retinal foveal thickness measures has a high diagnostic yield for PD.
PMID- 26414118
TI - Genetic susceptibility variants in parkinsonism.
AB - Parkinsonism is an umbrella term for a group of disorders characterized by the
clinical signs of tremor, bradykinesia, rigidity, and postural instability. On
neuropathologic examination parkinsonism can display alternate protein
pathologies (e.g. alpha-synucleinopathy or tauopathy) but the degeneration of
nigral neurons is consistent. The main forms of parkinsonism are, Parkinson's
disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA),
Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD). Genetic
studies from candidate gene, to unbiased genome-wide approaches including
association and next-generation sequencing have nominated a number of disease
determinants. Within this review we will highlight the genetic loci that are
associated with disease and discuss the implications and importance for a better
understanding of the genes involved and thus the underlying pathophysiology of
these disorders.
PMID- 26414120
TI - Surface Coating Constraint Induced Self-Discharging of Silicon Nanoparticles as
Anodes for Lithium Ion Batteries.
AB - One of the key challenges of Si-based anodes for lithium ion batteries is the
large volume change upon lithiation and delithiation, which commonly leads to
electrochemi-mechanical degradation and subsequent fast capacity fading. Recent
studies have shown that applying nanometer-thick coating layers on Si
nanoparticle (SiNPs) enhances cyclability and capacity retention. However, it is
far from clear how the coating layer function from the point of view of both
surface chemistry and electrochemi-mechanical effect. Herein, we use in situ
transmission electron microscopy to investigate the lithiation/delithiation
kinetics of SiNPs coated with a conductive polymer, polypyrrole (PPy). We
discovered that this coating layer can lead to "self-delithiation" or "self
discharging" at different stages of lithiation. We rationalized that the self
discharging is driven by the internal compressive stress generated inside the
lithiated SiNPs due to the constraint effect of the coating layer. We also
noticed that the critical size of lithiation-induced fracture of SiNPs is
increased from ~150 nm for bare SiNPs to ~380 nm for the PPy-coated SiNPs,
showing a mechanically protective role of the coating layer. These observations
demonstrate both beneficial and detrimental roles of the surface coatings,
shedding light on rational design of surface coatings for silicon to retain high
power and high capacity as anode for lithium ion batteries.
PMID- 26414121
TI - Restoration of impaired ecosystems: An ounce of prevention or a pound of cure?
Introduction, overview, and key messages from a SETAC-SER workshop.
AB - A workshop on Restoration of Impaired Ecosystems was held in Jackson, Wyoming, in
June 2014. Experts from Australia, Canada, Mexico, the United Kingdom, and the
United States in ecotoxicology, restoration, and related fields from both the
Society of Environmental Toxicology and Chemistry and the Society for Ecological
Restoration convened to advance the practice of restoring ecosystems that have
been contaminated or impaired from industrial activities. The overall goal of
this workshop was to provide a forum for ecotoxicologists and restoration
ecologists to define the best scientific practices to achieve ecological
restoration while addressing contaminant concerns. To meet this goal,
participants addressed 5 areas: 1) links between ecological risk assessment and
ecological restoration, 2) restoration goals, 3) restoration design, 4)
monitoring for restoration effectiveness and 5) recognizing opportunities and
challenges. Definitions are provided to establish a common language across the
varied disciplines. The current practice for addressing restoration of impaired
ecosystems tends to be done sequentially to remediate contaminants, then to
restore ecological structure and function. A better approach would anticipate or
plan for restoration throughout the process. By bringing goals to the forefront,
we may avoid intrusive remediation activities that close off options for the
desired restoration. Participants realized that perceived limitations in the site
assessment process hinder consideration of restoration goals; contaminant
presence will influence restoration goal choices; social, economic, and cultural
concerns can factor into goal setting; restoration options and design should be
considered early during site assessment and management; restoration of both
structure and function is encouraged; creative solutions can overcome
limitations; a regional focus is imperative; monitoring must occur throughout the
restoration process; and reciprocal transfer of knowledge is needed among
theorists, practitioners, and stakeholders and among varied disciplines.
PMID- 26414123
TI - Single dose oral analgesics for acute postoperative pain in adults - an overview
of Cochrane reviews.
AB - BACKGROUND: This is an updated version of the original Cochrane overview
published in Issue 9, 2011. That overview considered both efficacy and adverse
events, but adverse events are now dealt with in a separate overview.Thirty-nine
Cochrane reviews of randomised trials have examined the analgesic efficacy of
individual drug interventions in acute postoperative pain. This overview brings
together the results of those individual reviews and assesses the reliability of
available data. OBJECTIVES: To summarise the efficacy of pharmaceutical
interventions for acute pain in adults with at least moderate pain following
surgery who have been given a single dose of oral analgesic. METHODS: We
identified systematic reviews in the Cochrane Database of Systematic Reviews in
The Cochrane Library through a simple search strategy. All reviews were overseen
by a single review group, had a standard title, and had as their primary outcome
the number of participants with at least 50% pain relief over four to six hours
compared with placebo. For individual reviews, we extracted the number needed to
treat for an additional beneficial outcome (NNT) for this outcome for each
drug/dose combination, and also the percentage of participants achieving at least
50% maximum pain relief, the mean of mean or median time to remedication, and the
percentage of participants remedicating by six, eight, 12, or 24 hours. Where
there was adequate information for pairs of drug and dose (at least 200
participants, in at least two studies), we defined the addition of four
comparisons of typical size (400 participants in total) with zero effect as
making the result potentially subject to publication bias and therefore
unreliable. MAIN RESULTS: The overview included 39 separate Cochrane Reviews with
41 analyses of single dose oral analgesics tested in acute postoperative pain
models, with results from about 50,000 participants in approximately 460
individual studies. The individual reviews included only high-quality trials of
standardised design, methods, and efficacy outcome reporting. No statistical
comparison was undertaken.Reliable results (high quality information) were
obtained for 53 pairs of drug and dose in painful postsurgical conditions; these
included various fixed dose combinations, and fast acting formulations of some
analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief
over four to six hours compared with placebo. The proportion of participants
achieving this level of benefit varied from about 30% to over 70%, and the time
to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs
were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT
compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast
acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9
to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg
(1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4
to 2.6). Not all participants had good pain relief and, for many pairs of drug
and dose, 50% or more did not achieve at least 50% maximum pain relief over four
to six hours.Long duration of action (eight hours or greater) was found for
etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg,
naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000
mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500
mg, and oxycodone 5 mg (low quality evidence). No trial data were available in
reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and
tiaprofenic acid. Inadequate amounts of data were available for nine drugs and
doses, and data potentially susceptible to publication bias for 13 drugs and
doses (very low quality evidence). AUTHORS' CONCLUSIONS: There is a wealth of
reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast
acting formulations and fixed dose combinations of analgesics can produce good
and often long-lasting analgesia at relatively low doses. There is also important
information on drugs for which there are no data, inadequate data, or where
results are unreliable due to susceptibility to publication bias. This should
inform choices by professionals and consumers.
PMID- 26414122
TI - Higher Cognitive Function in Elderly Individuals with Previous Cataract Surgery:
Cross-Sectional Association Independent of Visual Acuity in the HEIJO-KYO Cohort.
AB - Cataract surgery improves visual acuity and drastically increases the capacity
for light reception to the retina. Although previous studies suggested that both
light exposure and visual acuity were associated with cognitive function, the
relationships between cataract surgery, visual acuity, and cognitive function
have not been evaluated in large populations. In this cross-sectional study, we
measured cognitive function using the Mini-Mental State Examination and best
corrected visual acuity in pseudophakic (previous cataract surgery) and phakic
(no previous cataract surgery) elderly individuals. Of 945 participants (mean age
71.7 years), 166 (17.6%) had pseudophakia and 317 (33.5%) had impaired cognitive
function (score <=26). The pseudophakic group showed significantly better visual
acuity than the phakic group (p = 0.003) and lower age-adjusted odds ratio (ORs)
for cognitive impairment (OR 0.66; p = 0.038). Consistently, in multivariate
logistic regression models, after adjusting for confounding factors, including
visual acuity and socioeconomic status, ORs for cognitive impairment were
significantly lower in the pseudophakic group than in the phakic group (OR 0.64;
95% confidence interval 0.43-0.96; p = 0.031). This association remained
significant in sensitivity analysis, excluding participants with low cognitive
score <=23 (n = 36). In conclusion, in a general elderly population, prevalence
of cognitive impairment was significantly lower in pseudophakic individuals
independently of visual acuity. The association was also independent of several
major causes of cognitive impairment such as aging, gender, obesity,
socioeconomic status, hypertension, diabetes, sleep disturbances, depressive
symptoms, and physical inactivity.
PMID- 26414125
TI - Patterns of Coexisting Lesions Detected on Magnetic Resonance Imaging and
Relationship to Incident Knee Osteoarthritis: The Multicenter Osteoarthritis
Study.
AB - OBJECTIVE: To identify patterns of coexisting lesions seen on magnetic resonance
imaging (MRI) in knees that are free of radiographic osteoarthritis (OA) and to
examine the relationship of these MRI-detected lesions to incident OA. METHODS:
Study subjects were individuals enrolled in the Multicenter Osteoarthritis Study,
a prospective cohort study. In each subject, 1 knee in which radiographic OA was
absent in both the tibiofemoral and patellofemoral joints at baseline was
selected for study, with followup for 84 months. We used a novel approach, latent
class analysis, to group the constellation of MRI lesions in each joint, i.e.,
cartilage damage, bone marrow lesion, meniscal tear, meniscal extrusion,
synovitis, and effusion, into a manageable number of subgroups. The association
of these subgroups with incident radiographic OA in the same joint was assessed
using logistic regression. RESULTS: Among 885 eligible knees (203 with incident
disease in the tibiofemoral joint, 64 with incident disease in the patellofemoral
joint), 4 latent subgroups in the tibiofemoral joint were identified (described
briefly as minimal lesions, mild lesions, moderate lesions [but limited meniscal
lesions], and severe lesions). The odds ratios of incident tibiofemoral joint OA
in the latter 3 subgroups (compared to the knees with minimal lesions as the
referent) were 5.6, 1.8, and 5.0, respectively. A similar set of 4 subgroups in
the patellofemoral joint was identified, except that the fourth subgroup had
limited meniscal lesions. The odds ratios of incident disease in the
patellofemoral joint were 3.8, 5.1, and 13.7 in the subgroups with mild lesions,
moderate lesions, and severe lesions, respectively. CONCLUSION: Different
patterns of coexisting MRI lesions, which have different implications with regard
to risk of knee OA, were identified. Meniscal damage seemed to play a different
role in the development of incident disease in tibiofemoral versus patellofemoral
joints.
PMID- 26414124
TI - Distinct Phenotypes of Cigarette Smokers Identified by Cluster Analysis of
Patients with Severe Asthma.
AB - RATIONALE: Smoking may have multifactorial effects on asthma phenotypes,
particularly in severe asthma. Cluster analysis has been applied to explore novel
phenotypes, which are not based on any a priori hypotheses. OBJECTIVES: To
explore novel severe asthma phenotypes by cluster analysis when including
cigarette smokers. METHODS: We recruited a total of 127 subjects with severe
asthma, including 59 current or ex-smokers, from our university hospital and its
29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained
during a 2-day hospital stay were used for cluster analysis. After clustering
using clinical variables, the sputum levels of 14 molecules were measured to
biologically characterize the clinical clusters. MEASUREMENTS AND MAIN RESULTS:
Five clinical clusters were identified, including two characterized by high pack
year exposure to cigarette smoking and low FEV1/FVC. There were marked
differences between the two clusters of cigarette smokers. One had high levels of
circulating eosinophils, high IgE levels, and a high sinus disease score. The
other was characterized by low levels of the same parameters. Sputum analysis
revealed increased levels of IL-5 in the former cluster and increased levels of
IL-6 and osteopontin in the latter. The other three clusters were similar to
those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and
female/obese. Key clinical variables were confirmed to be stable and consistent 1
year later. CONCLUSIONS: This study reveals two distinct phenotypes of severe
asthma in current and former cigarette smokers with potentially different
biological pathways contributing to fixed airflow limitation. Clinical trial
registered with www.umin.ac.jp (000003254).
PMID- 26414126
TI - An updated model to describe the neuroendocrine control of reproduction in
chickens.
AB - Since its first identification in quail 15 years ago, gonadotropin inhibitory
hormone (GnIH) has become a central regulator of reproduction in avian species.
In this review, we have revisited our original model published in 2009 to
incorporate recent experimental evidence suggesting that GnIH acts as a molecular
switch during the integration of multiple external and internal cues that allow
sexual maturation to proceed in chickens. Furthermore, we discuss the regulation
of a dual inhibitory/stimulatory control of the hypothalamo-pituitary-gonadal
axis involving the interaction between GnIH and gonadotropin releasing hormone
(GnRH). Finally, beyond seasonality, we also propose that GnIH along with this
dual control may be responsible for the circadian control of ovulation in
chickens, allowing eggs to be laid in a synchronized manner.
PMID- 26414127
TI - Expression and localization of vascular endothelial growth factor A (VEGFA) and
its two receptors (VEGFR1/FLT1 and VEGFR2/FLK1/KDR) in the canine corpus luteum
and utero-placental compartments during pregnancy and at normal and induced
parturition.
AB - VEGFA is one of the most potent known inducers of angiogenesis. However, the
function of angiogenic factors in the canine corpus luteum (CL) of pregnancy and
in the pregnant uterus and placenta has not yet been elucidated. Therefore, here
we investigated the expression and localization of VEGFA and its receptors
(VEGFR1/FLT1 and VEGFR2/FLK1/KDR) in the canine CL and utero-placental
compartments (ut-pl) throughout pregnancy until prepartum luteolysis.
Antigestagen-mediated effects on expression of VEGF system in ut-pl were
elucidated in mid-pregnant dogs. While displaying high individual variation, the
luteal VEGFA was elevated during pre-implantation and post-implantation, followed
by a decrease during mid-gestation, which was more pronounced at the mRNA level,
and showed constant expression afterwards. Within the uterus, it increased
following implantation and during mid-gestation in ut-pl compartments, but was
downregulated at prepartum luteolysis. Luteal VEGFR1 expression resembled that of
VEGFA; VEGFR2 remained unaffected throughout pregnancy. In ut-pl compartments,
both receptors increased gradually towards mid-gestation; a prepartum decrease
was observed for VEGFR1. Antigestagen-treatment resulted in decreased expression
of ut-pl VEGFR1. In the CL, VEGFA stained in luteal cells. Uterine signals of
VEGFA and its two receptors were observed in epithelial and vascular
compartments, and in myometrium. In placental labyrinth, additionally,
trophoblast stained positively. Luteal VEGFR1 was localized to the luteal cells
and tunica media of blood vessels, whereas VEGFR2 stained only in capillary
endothelial cells. The upregulation of luteal and the ut-pl VEGF system during
early gestational stages supports the increased vascularization rate during this
time. The diminishing effects of the prepartum endocrine milieu on VEGFA function
seem to be more pronounced in the ut-pl units.
PMID- 26414128
TI - Sialadenoma Papilliferum with Inverted Pattern in a Young Patient: A Case Report.
AB - BACKGROUND: Sialadenoma papilliferum (SP) is a rare, benign neoplasm of salivary
gland origin which manifests as an exophytic papillary excrescence of the mucosa.
Indeed, SP is both an exophytic proliferation of papillary stratified squamous
epithelium above the mucosal surface and an endophytic salivary ductal
proliferation beneath the mucosa. It arises predominantly in minor salivary
glands and usually affects patients in the age range of 32-87 years, with reports
in young patients being exceedingly rare. CASE REPORT: We report the case of a
previously healthy 20-year-old man diagnosed with a nodular mass in the upper lip
buccal mucosa. The tumor was excised and submitted for microscopic examination.
Histologic examination revealed a biphasic proliferation of papillary stratified
squamous and salivary ductal epithelia, both underneath the mucosal surface.
CONCLUSIONS: In this unique case, as the classical SP, the tumor had a biphasic
proliferation of squamous and ductal epithelia. However, unlike the classical SP,
both epithelia grew under the mucosal surface. As a result, it did not manifest
as an exophytic proliferation, but as a nodule. We excluded squamous papilloma,
inverted ductal papilloma, intraductal papilloma and mucoepidermoid carcinoma,
the principal entities in the differential diagnosis of SP, and concluded it was
an SP with inverted pattern.
PMID- 26414129
TI - Radiotherapy after hyperbaric oxygenation in malignant gliomas.
AB - OBJECTIVE: This review was to evaluate the efficacy and toxicity of radiation
therapy (RT) administered immediately after hyperbaric oxygen (HBO) therapy in
patients with high grade gliomas. RESEARCH DESIGN AND METHODS: PubMed, Embase,
ISI Web of Knowledge, and Cochrane databases were searched using combinations of
the following search terms: radiotherapy, hyperbaric oxygenation, chemotherapy,
glioma, brain tumor. Selection was limited to prospective studies involving
patients given HBO followed by RT for high-grade gliomas. Data extracted from
studies included the clinical research phase of the study, number of study arms,
number of patients, patient age and gender, glioma type and grade, pressure and
length of HBO, protocol of radiation therapy, duration of follow-up, and the
outcomes. MAIN OUTCOME MEASURES: Overall survival, time to progression, response
rate, tumor regression, and toxic effects associated with HBO plus RT treatment.
RESULTS: Literature search/screening yielded eight studies for analysis. Six of
the studies were single-arm in design and enrolled a total of 203 patients, of
whom 142 had grade IV gliomas and 61 had grade III gliomas. In these six studies,
all patients received HBO then RT. Two studies were double-arm in design, with 24
patients treated with HBO followed by RT and 26 patients treated with RT alone.
The findings from both the single- and double-arm studies indicated improved
outcomes (survival rate, progression free survival, time to progression, response
rate) with HBO and RT therapy. Reported toxicity included leucopenia, anemia,
thrombocytopenia, fever, loss of appetite, constipation, nausea, vomiting, and
liver dysfunction. The addition of HBO had minimal effect on toxicity or side
effects; across the eight studies, only one patient with severe middle ear
barotrauma had a complication directly related to HBO exposure. CONCLUSION: This
systematic reviews suggests that the addition of HBO to RT is tolerated and may
be beneficial in patients with high-grade gliomas.
PMID- 26414130
TI - [Public health international research: research scientist-field worker
partnership, interdisciplinarity and social role].
PMID- 26414131
TI - [Action-driven research and research-driven action: introduction to
interventional cancer research in human and social sciences].
PMID- 26414132
TI - [How to understand and facilitate return to school of high school students
treated for cancer: analysis of a sociology research-action project].
AB - Based on a sociology research-action project, this article analyses the specific
issue of return to school of high school students with cancer. Three detailed
cases, illustrating the global results of the study, are presented to highlight
the academic trajectories of these students. This situation has a particular
impact on juvenile sociability. Moreover, the education of these students does
not comply with French educational standards and is very complex for
professionals. Finally, social inequalities in education are reinforced by the
experience of serious illness, as pedagogical negotiations are even more complex
due to the fact that families are not familiar with school practices.
PMID- 26414133
TI - [Knowledge co-production and local transfer to reduce inequalities of access to
breast cancer screening].
AB - This paper describes a knowledge transfer experiment that has been conducted
since September 2012 in Argenteuil (Val d'Oise, France). This experiment is part
of an interventional research project called DeCL/C: "Knowledge translation on
social and spatial inequalities: a tool to raise local awareness and mobilization
to lessen cancer screening participation rate disparities': The project is
carried out by health geographers from Paris Ouest University (UPO) and the
National Association of Cities for Public Health (Elus, Sante Publique et
Territoires, ESPT). It encompasses two main components: intervention designed to
implement a knowledge co-production and transfer process among researchers,
stakeholders and decision makers at various levels. This knowledge concerns
social and spatial determinants of inequalities of access to breast cancer
screening programmes in cities. The research is multidisciplinary (geography,
sociology, political science, epistemology) and is designed to measure the impact
of this knowledge co-production and transfer in terms of actions in the targeted
cities (six cities in the Paris region) as well as the reduction of inequalities
of access to breast cancer screening programmes. This article, based on knowledge
transfer literature and an empirical experiment in Argenteuil, describes the
ongoing knowledge transfer process. It also highlights Argenteuil stakeholders'
and decision makers' interest in action and research. The analysis of the
knowledge co-production, sharing and ownership process by local actors a e both
"strategic" and "profound':
PMID- 26414134
TI - [Contribution of intervention to research in the context of a serious disease].
AB - By placing in perspective two ongoing studies based on interventional research
dynamics in the field of cancer, this article proposes a review of the specific
effects of this type of research. Although this approach is often poorly regarded
in the field of academic sociology, it is particularly adapted to the analysis of
ongoing processes, providing access to certain phenomena that would be otherwise
impossible to observe. The research worker's active involvement, the experience
that he/she shares with the subjects studied and the partnerships formed with
institutional bodies are the basis for the production of original scientific
knowledge, but also sometimes uncomfortable configurations.
PMID- 26414136
TI - [Cognitive dimensions of public health intervention: support for two primary
healthcare projects in rural areas].
AB - Some public health interventions are designed to support transformation of
primary health care services, by transforming an individual structure into a
collective healthcare structure. These interventions can be considered to be
knowledge-generating processes, as they help the actors involved in development
of a healthcare project to objectify and collectively share a common position on
the future supply of primary care. This shared vision helps them to adopt a
project approach in that this shared knowledge provides meaning to their action.
They can also help project stakeholders to know and recognize each other as
primary care partners, thus initiating the development of a health care team.
This approach helps to enhance and formalize coordination of existing practices
and event new coordination practices. Collective knowledge is therefore generated
by actors and capitalized by the third party. This knowledge can be used to
objectify individual experiences and consequently facilitates reflexivity of the
actors. Finally, the field response can be considered to be a dynamic conversion.
PMID- 26414135
TI - [Nurse action research on the cancer announcement system. Experience feedback
from the accompanying sociologist].
AB - This paper reports the action research conducted by a group of nurses working in
various hospitals belonging to the Onconord-llede- France (Val d'Oise) network
and involved in the setting-up of the paramedical cancer announcement system
following the 2005 Cancer plan from the point of view of the sociologist who
accompanied them. This analysis of the modalities and difficulties of
implementation of the new system allowed these nurses to develop their own self
assessment practice survey. They defined the best conaitions for setting up the
announcement visit and also achieved a better understanding of their position.
This research also opened up lines of reflection on the new organizational
configurations and the consequences on professional autonomy.
PMID- 26414137
TI - [Factors associated with drug prescription in general practice: a multicenter
cross-sectional study].
AB - OBJECTIVE: Iatrogenic, environmental and economic consequences of drug
prescription are public health issues. This study was designed to identify
physician, patient and consultation characteristics that influence drug
prescription in general practice. METHODS: A national multicentre cross-sectional
study was conducted in general practice from December 2011 to Apri/2012.
Bivariate analyses were performed, followed by multivariate analyses based on a
mixed model. RESULTS: At least one drug was prescribed in 16,626 (80.7%) of
20,600 consultations conducted by 128 practitioner. Apart from the number of
health problems managed (OR= 10.6 [8.8; 13.0] if :2 4), independent patient
related factors were female gender (OR= 1.1 [1.0; 1.2]), extreme ages (OR= 1.3
[1.1; 1.5]younger than 4 years, OR= 1.5 [1.3; 1.8] from 5 to 14 years, and OR=
1.3 {1.2; 1.5] older than 60 years vs. between 15 to 29 years), new patients (OR=
0.8 {0. 7; 0.9]), work accident or occupational disease (OR= 0.3 {0.3; 0.4]). For
the physician, drug prescription was linked to visits by pharmaceutical
representatives (OR = 1.6 [1.2; 2.0] if :2 5 times a week) but not to visits by
Public Health Insurance delegates or signature of the contract designed to
improve individual practices (CAP/). CONCLUSIONS: Independently of health
problems, patient and physician characteristics, including visits by
pharmaceutical representatives, influence drug prescription.
PMID- 26414138
TI - [Analysis of hospital outpatient care of a rare disease: cystic fibrosis].
AB - INTRODUCTION: Following the generalization of neonatal screening, the French CF
Care Network has become structured around 45 qualified centres, the French CF
Society, 2 national expertise centres, the Patient Registry and the National
Protocol of CF Care in collaboration with the Vaincre Ia Mucoviscidose patient
association. This organization and progress in treatment have resulted in the
outpatient follow-up of a growing number of patients. Since 2010, the CF Network
representatives have been conducting an assessment of outpatient follow-up to
identify difficulties in complying with national and international clinical
practice guidelines. METHODS: Two complementary quantitative and qualitative
approaches were used to characterize and quantify the activities carried out by
professionals in 8 centres both for outpatient visits and patient care
coordination. RESULTS: Two thirds of the 1,4 75 patients followed in the centres
were managed over the period, less than half (40%) of them attended outpatient
visits, but all of them were concerned by care coordination activities, whether
or not they were related to the visit. The core team (doctor, nurse, physio
therapist) is not mobilized at each scheduled outpatient visit as recommended.
Professionals devote 40% less time for follow-up in adult centres than in
paediatric centres, all activities included. The multidisciplinary outpatient
visit process is complicated by the lack of available resources and the
unsuitability of certain premises. DISCUSSION: With a constantly growing number
of patients, CF centres are struggling to comply with good clinical practice and
meet the specific needs of adult patients and transplant recipients. An upgrade
of professional resources and an update of the National Protocol appear to be
necessary.
PMID- 26414139
TI - [HIV infection. A chronic disease that redefines collaboration between general
practitioners and specialists. A qualitative study on opportunities and obstacles
to collaboration].
AB - PURPOSE: With the development of antiretroviral therapy, Human Immunodeficiency
Virus [HIV) infection has become a chronic disease. In order to develop an
efficient response to this new challenge, there is a need for closer
collaboration between specialized units and general practitioners. This article
identifies the opportunities for and the barriers to this collaboration. METHODS:
Semi-structured interviews were conducted with patients living with HIV, general
practitioners working in multidisciplinary group practice using the capitation
system and infectiologists from one Belgian urban area. Interviews focused one
xperiences and expectations in relation to diagnosis, follow-up and collaboration
between general practitioners and infectiologists. RESULTS: Overall,
infectiologists and general practitioners aspire to improved communication and
collaboration. There are overlaps between general practitioner's and
infectiologist's field of action. The general practitioner's intervention is
sometimes restricted to common uncomplicated or psychosocial problems, in the
context of unplanned and short contacts.Infectiologists prefer to focus on HIV
problems, leaving general practitioners to take care of these patients' other
health problems. The patient may be an obstacle to greater involvement of general
practitioners due to fear of stigmatization from his family and social circle or
lack of confidence in the general practitioner's skills. CONCLUSION: This
research underlines the difficulties and gaps in the care of HIV patients and
provides preliminary explanations for the lack of active cooperation between
general practitioners and infectiologists. Overlaps between the areas of
professional skills can result in uncovered aspects of care, which can have a
negative impact on patients, but also on general practitioners and
infectiologists. Collaboration between general practitioners and infectiologists
should be based on a concerted decision, with clear allocation of tasks, taking
into account the patient's expectations.
PMID- 26414140
TI - [Use of medical and administrative databases to measure social health
inequalities].
AB - OBJECTIVE: The ability to measure social health inequalities is a prerequisite to
the implementation of local policies designed to reduce such inequalities. The
absence of individual socioeconomic data in medical and administrative databases
does not allow direct evaluation of those inequalities. The objective of this
study is to propose a method of measurement of social health inequalities from
national health insurance databases and a validated deprivation index. METHODS:
27 health care and prevention indicators were constructed to identify social
health inequalities. Medical and administrative databases were cross-matched with
the European Deprivation Index, completed by a potential spatial accessibility
indicator in order to take into account the spatial distribution health care
services. RESULTS: The study population comprised data devived from the three
main health insurance schemes, and represents 89% of the population of the Midi
Pyrenees region. 98% were able to be geographically coded. The 27 indicators were
therefore calculated on a total of 2,574,310 individuals, i.e. 87% of the
regional population. CONCLUSION: This study illustrates the value of using
medical and administrative data to create databases allowing measurement of
social health inequalities and their variations within a region. The proposed
indicators could be used as decision-making tools for the selection of zones of
intervention and to assess the impact of public policies designed to reduce
social health inequalities.
PMID- 26414141
TI - [Theoretical basis for health system performance assessment].
AB - In France, the search for improved performance in the public sector, considered
to reflect optimization of public services, has undergone various phases since
the second World War. Public policy assessment has also considerably developed
since the 1990s. The various reforms and resulting programmes have contributed to
changing the French public administration from a means-based approach to a
results-based approach, an essential step to improve performance according to the
New Public Management paradigm. Other theories have also been proposed concerning
performance assessment in the public sector, especially the medical care sector.
The primary objective of this article is to propose a theoretical framework for
the concept of performance and performance assessment in the health sector. The
authors also propose a reading grid of the main theories concerning application
of performance assessment in the health care sector.
PMID- 26414142
TI - [The non-uptake of prenatal care in Burkina Faso].
AB - INTRODUCTION: Despite the importance of prenatal care to decrease maternal and
neonatal mortality, uptake remains suboptimal in Burkina Faso. This article
documents the reasons for non-uptake of prenatal care, by focusing on women who
either completely renounce or delay their access to prenatal care. METHODS:
Qualitative data collection was performed in the rural town of Kokologho from
October 2013 to january 2014. Different collection methods were used: participant
observation, twenty-two individual semi-structured interviews with women who
accessed prenatal care as a late option and eight informal interviews with key
informants identified in the community. RESULTS: Thematic analysis revealed four
barriers against the effective use of prenatal care by women: (1) lack of
knowledge about the prenatal care schedule and purpose (2) perception of
pregnancy and prenatal care (3) socioeconomic barriers: direct payment for
prenatal care and the limited autonomy of women, and (4) perception of the
quality of prenatal care. DISCUSSION: Based on these observations, non-uptake of
prenatal care is discussed using different types of explanatory typologies
adopted for this study: non-knowledge, non-claiming by choice or constraints and
non-reception of care. This theoretical approach reveals that failures in
healthcare services as well as the dichotomy between social representations and
medical standards of pregnancy and prenatal care contribute to exclude some women
from the prenatal care system.
PMID- 26414143
TI - [Change management: An analysis of actors; perceptions about technical assistance
in the Democratic Republic of Congo].
AB - INTRODUCTION: Technical assistance (TA) is a common component of health system
strengthening interventions. This type of intervention is too often designed and
evaluated according to a logic that fails to take into account social complexity.
Actors' perceptions are one element of this complexity. This article presents a
study conducted in the Democratic Republic of Congo designed to identify
perceptions concerning two types of technical support providers for health system
strengthening: long-term technical assistants (agents of development agencies)
and provincial technical advisors (agents of the Ministry of Health). METHODS:
Interviews were conducted with an innovative tool inspired by the principles of
systems thinking. Interviewees were actors involved in a TA intervention in the
province of Bandundu. Their expectations regarding TA providers were identified
in terms of personal characteristics (knowledge, know-how and interpersonal
skills), roles, and styles of interaction for capacity building
("interventionist/ prescriptive axes"). RESULTS AND DISCUSSION: Interviewees
emphasized the importance of mutual learning and the quality of interactions,
which depends on TA provider's interpersonal skills and mutual willingness.
Perceptions of TA provider's characteristics tend to be similar, but several
differences were observed concerning the expectations about the roles of TAs, and
the style that should be adopted for capacity building. Ignoring these
differences in expectations may be a threat to the effectiveness of TA.
PMID- 26414144
TI - [Negotiation of a heath policy controversy: application of an indirect dialogue
approach to performance-based financing in sub-Saharan Africa].
AB - OBJECTIVES: This article assesses the controversy around performance-based
financing (PBF) and its contribution to the reform of health systems. It aims to
reduce tensions between the different camps by restructuring the debate. METHODS:
Our approach was to organize an indirect dialogue between critics and supporters
of PBF, based on the framework developed by Norman Daniels. This analytical
framework is non-partisan and uses clear and objective criteria. The interviews
were carried out in two rounds (first the critics, then the supporters) and were
then analyzed. Parts of answers were regrouped according to the most common
sectoral themes while also highlighting major areas of disagreement. RESULTS: The
interviews revealed some areas of convergence around PBF; the strategy is
considered to be a complementary strategy to other strategies; such as those
which aim to improving financial access to health care. The analysis also
revealed disagreements based on misunderstandings of claims often ascribed to
PBF, or lack of sufficient evidence, or asymmetrical information between experts.
CONCLUSIONS: Several questions polarize PBF discussions. However, better
structuring of convergent and divergent areas and arguments should facilitate a
synthesis, at least to some extent. Experts need to adopt an objective approach
with universally accepted criteria, for the benefit of all.
PMID- 26414146
TI - A proof of concept study investigating the feasibility of combining iPAM robot
assisted rehabilitation with functional electrical stimulation to deliver whole
arm exercise in stroke survivors.
AB - Rehabilitation robots can provide exercise for stroke survivors with weakness at
the shoulder and elbow, but most do not facilitate hand movements. The aim was to
combine robotics and functional electrical stimulation to facilitate exercise in
stroke survivors with upper limb impairment. iPAM Mk II was used to assist active
reaching in combination with an Odstock Pace stimulator to assist hand opening.
The ABILHAND, Action Research Arm Test (ARAT) and the Stroke Impact Scale (SIS)
were recorded at baseline and completion. Nine participants (eight males and one
female; mean age = 58 years) were recruited; mean time since stroke was 16 months
(range = 6-64). The ABILHAND at baseline was -2.73, improving to -1.45 at follow
up (p = 0.038). The ARAT changed from 4.1 to 2.6 (p = 0.180), and the SIS from 49
to 60 (p = 0.019). This study demonstrates that it is possible to combine two
technologies in stroke rehabilitation.
PMID- 26414148
TI - COHORT EFFECTS OF SUICIDE MORTALITY ARE SEX SPECIFIC IN THE RAPIDLY DEVELOPED
HONG KONG CHINESE POPULATION, 1976-2010.
AB - BACKGROUND: To examine temporal variations of age, period, and cohort on suicide
mortality rate in Hong Kong (HK) from 1976 to 2010, and speculate the
macroenvironmental mechanisms of the observed trends. METHODS: Poisson age-period
cohort modeling was used to delineate the effects of age, period, and cohort on
suicide mortality. Analysis by sex was also conducted to examine if gender
difference exists for suicidal behaviours. RESULTS: Age-cohort model provides the
best fit to the mortality data, implying that the cohort effect is likely to
explain more of the contributions to HK's suicide mortality pattern than the
period effect. Risk of suicide mortality increases nonlinearly with age and
accelerates after age 65-69 for both sexes. Moreover, the cohort effects differ
between the sexes-risk of mortality increases continually for men born after
1961, but no change is observed for women since the 1941 cohort. CONCLUSIONS:
With increased risk of suicide mortality in younger cohorts and the age effect of
suicide mortality, we may see future increase in suicide mortality as these
younger cohorts age. Further studies are needed to clarify plausible associations
between broader sociohistorical changes in the population impacting psychological
risk factors and suicidal behaviour to better inform suicide prevention
strategies.
PMID- 26414149
TI - Successful treatment of HCV-associated cryoglobulinemia with
ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin: A case report.
AB - Cryoglobulinemia is an important extrahepatic manifestation of chronic hepatitis
C virus infection. Current treatments are suboptimal, resulting in relapse or
refractoriness in 30-40% of patients. Hereby, we describe the case of a 40-year
old man with severe hepatitis C virus-associated cryoglobulinemia, effectively
treated with an interferon-free combination regimen. The patient was treated for
12 weeks with ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin. Rapid
clinical and immunological response, i.e., the resolution of symptoms and
disappearance of serum cryoglobulins, ensued as early as 4 weeks after initiating
direct acting antiviral therapy. Our reported case directs the attention to the
possible consequences and importance of new, effective, interferon-free antiviral
treatments in devastating lymphoproliferative and immunological manifestations of
chronic hepatitis C virus infection.
PMID- 26414147
TI - Inefficiencies and High-Value Improvements in U.S. Cervical Cancer Screening
Practice: A Cost-Effectiveness Analysis.
AB - BACKGROUND: Studies suggest that cervical cancer screening practice in the United
States is inefficient. The cost and health implications of nonadherence in the
screening process compared with recommended guidelines are uncertain. OBJECTIVE:
To estimate the benefits, costs, and cost-effectiveness of current cervical
cancer screening practice and assess the value of screening improvements. DESIGN:
Model-based cost-effectiveness analysis. DATA SOURCES: New Mexico HPV Pap
Registry; medical literature. TARGET POPULATION: Cohort of women eligible for
routine screening. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION:
Current cervical cancer screening practice; improved adherence to guidelines
based screening interval, triage testing, diagnostic referrals, and precancer
treatment referrals. OUTCOME MEASURES: Reductions in lifetime cervical cancer
risk, quality-adjusted life-years (QALYs), lifetime costs, incremental cost
effectiveness ratios, and incremental net monetary benefits (INMBs). RESULTS OF
BASE-CASE ANALYSIS: Current screening practice was associated with lower health
benefit and was not cost-effective relative to guidelines-based strategies.
Improvements in the screening process were associated with higher QALYs and small
changes in costs. Perfect adherence to screening every 3 years with cytologic
testing and adherence to colposcopy/biopsy referrals were associated with the
highest INMBs ($759 and $741, respectively, at a willingness-to-pay threshold of
$100,000 per QALY gained); together, the INMB increased to $1645. RESULTS OF
SENSITIVITY ANALYSIS: Current screening practice was inefficient in 100% of
simulations. The rank ordering of screening improvements according to INMBs was
stable over a range of screening inputs and willingness-to-pay thresholds.
LIMITATION: The effect of human papillomavirus vaccination was not considered.
CONCLUSIONS: The added health benefit of improving adherence to guidelines,
especially the 3-year interval for cytologic screening and diagnostic follow-up,
may justify additional investments in interventions to improve U.S. cervical
cancer screening practice. PRIMARY FUNDING SOURCE: U.S. National Cancer
Institute.
PMID- 26414150
TI - The crisis in pediatric cardiac transplantation: How soon is now?
PMID- 26414151
TI - Human leukocyte antigen mismatching and survival after lung transplantation in
adult and pediatric patients with cystic fibrosis.
AB - INTRODUCTION: The influence of human leukocyte antigen (HLA) mismatching on
survival in adult and pediatric patients with cystic fibrosis (CF) after lung
transplantation (LTx) is unknown. METHODS: The United Network for Organ Sharing
database was queried from 1987 to 2013 to determine the influence of HLA
mismatching on survival in adult and pediatric CF LTx recipients by assessing the
association of HLA mismatching with survival in first-time adult (aged >= 18
years) and pediatric (aged <18 years) recipients. RESULTS: Of 3149 adult and 489
pediatric patients with CF, 3145 and 489 were used for univariate Cox analysis,
2687 and 363 for Kaplan-Meier survival analysis, and 2073 and 257 for
multivariate Cox analysis, respectively. Univariate analyses in adult and
pediatric patients with CF demonstrated conflicting associations between HLA
mismatching and survival (adult hazard ratio [HR], 1.0; 95% confidence interval
[CI], 0.97-1.1; P = .45 vs pediatric HR, 0.87; 95% CI, 0.77-0.99; P = .032).
Multivariate Cox models including both pediatric and adult patients confirmed
that HLA mismatching had an initially protective effect at young ages (HR, 0.85;
95% CI, 0.73-0.99; P = .044) and that this protective effect diminished at older
ages and was no longer associated with survival at P < .05 beyond age 10 years.
CONCLUSIONS: HLA mismatching has significantly different implications for
survival after LTx in adult compared with pediatric patients with CF.
PMID- 26414152
TI - Surgical resection of circumferential epicardial adipose tissue hypertrophy: Case
report and systematic review of the literature.
PMID- 26414153
TI - Cellular signaling pathways implicated in metastasis of colorectal cancer and the
associated targeted agents.
AB - Colorectal cancer (CRC) is the third leading cancer worldwide and CRC-related
death is mainly attributed to metastasis. Many cellular signaling pathways have
been demonstrated to be aberrant in colorectal tumors, and some of them lead to
the acquisition of malignant phenotypes. Therefore, the evaluation of signaling
pathways implicated in CRC metastasis is urgent for further understanding of CRC
progression and pharmacotherapy. This review focuses on several novel cellular
signaling pathways associated with CRC metastasis, including Wnt/beta-catenin,
p53, COX, TGF-beta/Smad, NF-kappaB, Notch, VEGF and JAKs/STAT3 signaling
pathways. Targeted agents developed based on these pathways are also briefly
discussed.
PMID- 26414154
TI - Assessment of strobilurin fungicides' content in soya-based drinks by liquid
micro-extraction and liquid chromatography with tandem mass spectrometry.
AB - Seven strobilurin fungicides were pre-concentrated from soya-based drinks using
dispersive liquid-liquid micro-extraction (DLLME) with a prior protein
precipitation step in acid medium. The enriched phase was analysed by liquid
chromatography (LC) with dual detection, using diode array detection (DAD) and
electrospray-ion trap tandem mass spectrometry (ESI-IT-MS/MS). After selecting 1
undecanol and methanol as the extractant and disperser solvents, respectively,
for DLLME, the Taguchi experimental method, an orthogonal array design, was
applied to select the optimal solvent volumes and salt concentration in the
aqueous phase. The matrix effect was evaluated and quantification was carried out
using external aqueous calibration for DAD and matrix-matched calibration method
for MS/MS. Detection limits in the 4-130 and 0.8-4.5 ng g(-1) ranges were
obtained for DAD and MS/MS, respectively. The DLLME-LC-DAD-MS method was applied
to the analysis of 10 different samples, none of which was found to contain
residues of the studied fungicides.
PMID- 26414155
TI - Psychometric evaluation of the Concerns of Social Reprisal Scale: Further
explicating the roots of fear of positive evaluation.
AB - Fear of positive evaluation (FPE) has been proposed to be an important feature of
social anxiety disorder (SAD) and to be rooted, at least partly, in concerns of
social reprisal due to positive impressions. In order to formally test this
hypothesis, the Concerns of Social Reprisal Scale (CSRS) was developed. The
purpose of the present series of studies was to examine the psychometric profile
of the CSRS across several independent samples including: a large (n=981)
undergraduate sample; a clinical sample of individuals diagnosed with social
anxiety disorder (n=27), and a demographically-matched subsample of healthy
control participants (n=24). The factorial validity, internal consistency, and
construct validity of the CSRS were examined. Results across both studies
provided support for the psychometric profile of the CSRS. The implications of
concerns of social reprisal for the assessment of social anxiety symptoms,
theoretical models of fear of evaluation and SAD, and their potential clinical
utility with regard to treating SAD are discussed.
PMID- 26414156
TI - Economic analysis of athletic team coverage by an orthopedic practice.
AB - OBJECTIVE: Coverage of high school football by orthopedic sports medicine
specialists is considered standard of care in many localities. Determining the
economic viability of this endeavor has never been investigated. The primary
purpose of the present investigation was to perform an economic analysis of local
high school sports coverage by an orthopedic sports medicine practice. METHODS:
From January 2010 to June 2012, a prospective injury report database was used to
collect sports injuries from five high school athletic programs covered by a
single, private orthopedic sports medicine practice. Patients referred for
orthopedic care were then tracked to determine expected cost of care (potential
revenue). Evaluation and management codes and current procedure terminology codes
were obtained to determine the value of physician visits and surgical care
rendered. Overhead costs were calculated based on historical rates within our
practice and incorporated to determine estimated profit. RESULTS: 19,165 athletic
trainer contacts with athletes playing all sports, including both those 'on
field' and in the training room, resulted in 473 (2.5%) physician referrals. The
covering orthopedic practice handled 89 (27.9%) of the orthopedic referrals. Of
orthopedic physician referrals, 26 (5.4%) required orthopedic surgical treatment.
The covering team practice handled 17/26 (65%) surgical cases. The total revenue
collected by the covering team practice was $26,226.14. The overhead cost of
treatment was $9441.41. Overall estimated profit of orthopedic visits and
treatment during this period for the covering practice was $16,784.73.
CONCLUSIONS: The covering team practice handled 28% of the orthopedic referrals,
65% of the surgical cases and captured 59% of the potential profit. An increase
in physician referrals could increase the benefit for orthopedic surgeons.
PMID- 26414158
TI - Time Course of Coagulation and Fibrinolytic Parameters in Patients with Traumatic
Brain Injury.
AB - Traumatic brain injury (TBI) has long been associated with coagulopathy; however,
the time course of coagulation/fibrinolytic parameters in the acute phase of TBI
remains unclear. The purpose of the study was to analyze the time course of
coagulation/fibrinolytic parameters in the acute phase of TBI and to elucidate
parameter relationships to prognosis. We retrospectively evaluated 234 patients
with severe isolated TBI with initial blood samples obtained no more than 1 h
after injury. Platelet count, prothrombin time, activated partial thromboplastin
time (aPTT), plasma levels of fibrinogen, and D-dimer were measured on arrival in
the emergency department and 3, 6, and 12 h after injury. Multivariate logistic
regression analysis was performed to identify risk factors for poor prognosis at
each time point. From hospital admission to 12 h after injury, an elevated D
dimer level was a significant negative prognostic indicator (admission: p <
0.0001; 3 h after injury: p = 0.0005; 6 h after injury: p = 0.005; 12 h after
injury: p = 0.0009). An upward trend of aPTT on admission and 3 h after injury
was also a significant negative prognostic indicator (admission: p = 0.0011; 3 h
after injury: p = 0.013). On multivariate logistic regression analysis, which
included all initial variables, independent risk factors for poor prognosis
included older age (p = 0.0005), low Glasgow Coma Scale score (p < 0.0001), high
Abbreviated Injury Score (p = 0.015), aPTT >30.2 sec (p = 0.019), and elevated D
dimer level (p = 0.0005). We concluded that D-dimer is the best
coagulation/fibrinolytic parameter to monitor for prediction of outcome.
PMID- 26414157
TI - Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced
Epigenetic Changes.
AB - Drugs of abuse modify behavior by altering gene expression in the brain. Gene
expression can be regulated by changes in DNA methylation as well as by histone
modifications, which alter chromatin structure, DNA compaction and DNA
accessibility. In order to better understand the molecular mechanisms directing
drug-induced changes in chromatin structure, we examined DNA-nucleosome
interactions within promoter regions of 858 genes in human neuroblastoma cells
(SH-SY5Y) exposed to nicotine or cocaine. Widespread, drug- and time-resolved
repositioning of nucleosomes was identified at the transcription start site and
promoter region of multiple genes. Nicotine and cocaine produced unique and
shared changes in terms of the numbers and types of genes affected, as well as
repositioning of nucleosomes at sites which could increase or decrease the
probability of gene expression based on DNA accessibility. Half of the drug
induced nucleosome positions approximated a theoretical model of nucleosome
occupancy based on physical and chemical characteristics of the DNA sequence,
whereas the basal or drug naive positions were generally DNA sequence
independent. Thus we suggest that nucleosome repositioning represents an initial
dynamic genome-wide alteration of the transcriptional landscape preceding more
selective downstream transcriptional reprogramming, which ultimately
characterizes the cell- and tissue-specific responses to drugs of abuse.
PMID- 26414160
TI - Effect of bladder wall thickness on miniature pneumatic artificial muscle
performance.
AB - Pneumatic artificial muscles (PAMs) are actuators known for their high power to
weight ratio, natural compliance and light weight. Due to these advantages, PAMs
have been used for orthotic devices and robotic limbs. Small scale PAMs have the
same advantages, as well as requiring greatly reduced volumes with potential
application to prostheses and small scale robotics. The bladder of a PAM affects
common actuator performance metrics, specifically: blocked force, free
contraction, hysteresis, and dead-band pressure. This paper investigates the
effect that bladder thickness has on static actuation performance of small scale
PAMs. Miniature PAMs were fabricated with a range of bladder thicknesses to
quantify the change in common actuator performance metrics specifically: blocked
force, free contraction, and dead-band pressure. These PAMs were then
experimentally characterized in quasi-static conditions, where results showed
that increasing bladder wall thickness decreases blocked force and free
contraction, while dead-band pressure increases. A nonlinear model was then
applied to determine the structure of the stress-strain relationship that enables
accurate modeling and the minimum number of terms. Two nonlinear models are
compared and the identified parameters are analyzed to study the effect of the
bladder thickness on the model.
PMID- 26414159
TI - A 22-Year Follow-up Study of Long-term Cardiac Outcome and Predictors of Survival
in Friedreich Ataxia.
AB - IMPORTANCE: Friedreich ataxia (FRDA) is the most common genetic sensory ataxia,
and myocardial involvement is a major determinant of survival. OBJECTIVE: To
assess FRDA survival and cardiac outcome to adapt future therapeutic trials.
DESIGN, SETTING, AND PARTICIPANTS: In a longitudinal follow-up study, all
patients with genetically confirmed FRDA seen in the reference center and
referred for cardiac evaluation (standard 12-lead electrocardiogram and
transthoracic echocardiography) to the cardiology department were enrolled and
followed up from April 27, 1990, to July 31, 2013. The setting was the French
National Reference Center for Rare Diseases and the Department of Cardiology,
Salpetriere University Hospital, Paris, France. In total, 138 patients with FRDA
were followed up. Among 133 patients homozygous for expanded GAA repeats, the
mean (SD) age was 31 (10) years (age range, 11-62 years), with a mean (SD) age at
disease onset of 16 (8) years (age range, 3-50 years) and a mean (SD) age at
first wheelchair use of 26 (9) years (age range, 11-64 years). Cardiac
hypertrophy was present in 57.9% (77 of 133), and electrocardiography was normal
in 6.8% (9 of 133). MAIN OUTCOMES AND MEASURES: Long-term cardiac outcome and
predictors of survival in FRDA. RESULTS: After a mean (SD) follow-up of 10.5
(5.5) years (range, 0.6-23.0 years), the 10-year survival rate was 88.5%. In
80.0% of patients (12 of 15), death was due to cardiac causes. Predictors of
survival were a shorter GAA repeat length on the smaller allele of the frataxin
gene (hazard ratio [HR], 1.85; 95% CI, 1.28-2.69), left ventricular ejection
fraction (HR, 0.42; 95% CI, 0.20-0.89), and left ventricular mass index (HR,
1.19; 95% CI, 1.04-1.36). Two cardiac evolutions were distinguished with a group
based trajectory model, including a low-risk cardiac group (78.6% [81 of 103]
with normal ejection fraction at baseline that declined slightly over time but
remained within the normal range) and a high-risk cardiac group (21.4% [22 of
103] in which the ejection fraction progressively declined during follow-up). The
patients with the worse cardiac evolution had longer GAA repeats. Neurological
impairment was not predictive of cardiac change over time. CONCLUSIONS AND
RELEVANCE: Survival in FRDA is determined by cardiac complications, which are
dependent on the mutation (ie, the size of the expanded GAA repeat). Patients
with progressive decline of the left ventricular ejection fraction had a worse
prognosis. This finding demonstrates that cardiac follow-up is important in FRDA
to identify individuals at risk for further cardiac complications.
PMID- 26414161
TI - Steep Decline and Cessation in Seed Dispersal by Myrmica rubra Ants.
AB - Myrmecochorous diaspores bear a nutrient-rich appendage, the elaiosome,
attractive to ant workers that retrieve them into the nest, detach the elaiosome
and reject the seed intact. While this interaction is beneficial for the plant
partner by ensuring its seed dispersal, elaiosome consumption has various effects
-positive, negative or none - on ants' demography and survival, depending on both
the ant/plant species involved. In this context, the contribution of ants to seed
dispersal strongly varies according to the ant/plant pairs considered. In this
paper, we investigate whether the dynamics of myrmecochory also vary on a
temporal scale, for a given pair of partners: Myrmica rubra ants and Viola
odorata seeds. During their first encounter with seeds, ants collect all the
diaspores and eat the majority of elaiosomes. Both the harvesting effort and the
elaiosome consumption decline when seeds are offered on the next week and
completely cease for the following weeks. This is related to a decrease in the
number of foragers reaching the food source, as well as to a reduced probability
for an ant contacting a seed to retrieve it. Seed retrieval is not reactivated
after seven weeks without any encounter with V. odorata seeds. By contrast, naive
ant colonies only fed with fruit flies do not show a decline of prey harvesting
of which the speed of retrieval even increases over the successive weeks.
Myrmecochory may thus be labile at the scale of a fruiting season due to the
ability of ants to steeply tune and cease for several months the harvesting of
these seemingly poorly rewarding items and to maintain cessation of seed
exploitation. The present study emphasizes the importance of a long-lasting
follow up of the myrmecochory process, to assess the stability of this ant-plant
partnership and to identify mechanisms of adaptive harvesting in ants.
PMID- 26414162
TI - Nonbiaryl and Heterobiaryl Atropisomers: Molecular Templates with Promise for
Atropselective Chemical Transformations.
PMID- 26414163
TI - Phylogeography of the Golden Jackal (Canis aureus) in India.
AB - The golden jackal (Canis aureus) is one of the most common and widely distributed
carnivores in India but phylogeographic studies on the species have been limited
across its range. Recent studies have observed absence of mitochondrial (mt) DNA
diversity in European populations while some North African populations of golden
jackal were found to carry gray wolf (Canis lupus lupaster) mtDNA lineages. In
the present study, we sequenced 440 basepairs (bp) of control region (CR) and 412
bp of cytochrome b (cyt b) gene of mtDNA from 62 golden jackals sampled from
India (n = 55), Israel (n = 2) and Bulgaria (n = 5), to obtain a total of
eighteen haplotypes, comprising sixteen from India and one each from Israel and
Bulgaria. Except for three previously described haplotypes represented by one cyt
b and one CR haplotype both from India, and one CR haplotype from Bulgaria, all
haplotypes identified in this study are new. Genetic diversity was high in golden
jackals compared to that reported for other canids in India. Unlike the
paraphyletic status of African conspecifics with the gray wolf, the Indian (and
other Eurasian) golden jackal clustered in a distinct but shallow monophyletic
clade, displaying no evidence of admixture with sympatric and related gray wolf
and domestic dog clades in the region. Phylogeographic analyses indicated no
clear pattern of genetic structuring of the golden jackal haplotypes and the
median joining network revealed a star-shaped polytomy indicative of recent
expansion of the species from India. Indian haplotypes were observed to be
interior and thus ancestral compared to haplotypes from Europe and Israel, which
were peripheral and hence more derived. Molecular tests for demographic expansion
confirmed a recent event of expansion of golden jackals in the Indian
subcontinent, which can be traced back ~ 37,000 years ago during the late
Pleistocene. Our results suggest that golden jackals have had a potentially
longer evolutionary history in India than in other parts of the world, although
further sampling from Africa, the Middle East and south-east Asia is needed to
test this hypothesis.
PMID- 26414164
TI - Impact of androgen and dietary advanced glycation end products on female rat
liver.
AB - BACKGROUND/AIMS: Advanced glycation end products (AGEs) have been related to a
wide range of liver disorders including hyperandrogenic states such as the
Polycystic Ovary Syndrome (PCOS). The aim of the present study is to evaluate the
potential impact of dietary glycotoxins exposure and androgen excess on hepatic
histology and biochemistry in an androgenized female rat model. METHODS: The
study population consisted of 80 female Wistar rats, divided in 3 groups, a group
of prepubertal (Group A, n=30) and adult rats (Group B, n=20) that were
androgenized via subcutaneous implantation of dihydrotestosterone-containing
pellets as well as a group of adult non-androgenized rodents (Group C, n=30). All
groups were randomly assigned either to a high-AGE or low-AGE diet for 3 months.
RESULTS: Rats fed with a high-AGE diet exhibited significantly elevated levels of
gamma-glutamyl transferase (x03B3;GT) (p<=0.0002) and indices of AGE
immunostaining in liver tissue (p<0.01) when compared to the respective low-AGE
group, while aspartate aminotransferase (AST) levels were affected only in non
androgenized animals (p=0.0002). Androgenization per se constitutes an
aggravating factor as demonstrated by the elevated x03B3;GT levels in adult
androgenized animals compared to non-androgenized, independent of diet content
(p=0.0002) and by the elevated AST and alanine aminotransferase (ALT) levels in
low-AGE subgroups (adult androgenized vs. non-androgenized, p=0.0002) followed by
increased immunohistochemical AGE deposition in hepatocytes of the latter
categories (p=0.0007). CONCLUSION: The present study suggests that androgens and
glycotoxins may contribute synergistically to distort hepatic physiology and
function as observed in hyperandrogenic conditions.
PMID- 26414165
TI - Stem cells in clinical trials for treatment of retinal degeneration.
AB - INTRODUCTION: After decades of basic science research involving the testing of
regenerative strategies in animal models of retinal degenerative diseases, a
number of clinical trials are now underway, with additional trials set to begin
shortly. These efforts will evaluate the safety and preliminary efficacy of cell
based products in the eyes of patients with a number of retinal conditions,
notably including age-related macular degeneration, retinitis pigmentosa and
Stargardt's disease. AREAS COVERED: This review considers the scientific work and
early trials with fetal cells and tissues that set the stage for the current
clinical investigatory work, as well the trials themselves, specifically those
either now completed, underway or close to initiation. The cells of interest
include retinal pigment epithelial cells derived from embryonic stem or induced
pluripotent stem cells, undifferentiated neural or retinal progenitors or cells
from the vascular/bone marrow compartment or umbilical cord tissue. EXPERT
OPINION: Degenerative diseases of the retina represent a popular target for
emerging cell-based therapeutics and initial data from early stage clinical
trials suggest that short-term safety objectives can be met in at least some
cases. The question of efficacy will require additional time and testing to be
adequately resolved.
PMID- 26414166
TI - Psychological distance reduces literal imitation: Evidence from an imitation
learning paradigm.
AB - The present experiments tested the hypothesis that observers engage in more
literal imitation of a model when the model is psychologically near to (vs.
distant from) the observer. Participants learned to fold a dog out of towels by
watching a model performing this task. Temporal (Experiment 1) and spatial
(Experiment 2) distance from the model were manipulated. As predicted,
participants copied more of the model's specific movements when the model was
near (vs. distant). Experiment 3 replicated this finding with a paper-folding
task, suggesting that distance from a model also affects imitation of less
complex tasks. Perceived task difficulty, motivation, and the quality of the end
product were not affected by distance. We interpret the findings as reflecting
different levels of construal of the model's performance: When the model is
psychologically distant, social learners focus more on the model's goal and
devise their own means for achieving the goal, and as a result show less literal
imitation of the model. (PsycINFO Database Record
PMID- 26414167
TI - Carrying a biological "backpack": Quasi-experimental effects of weight status and
body fat change on perceived steepness.
AB - The apparent steepness of hills and stairs is overestimated in explicit
perception. These overestimations are malleable in that when physiological
resources are compromised, apparent steepness is further overestimated. An
alternative explanation of these experimental findings attributes them to demand
characteristics. This article tests the relationship between estimated steepness
and naturally occurring differences in body composition. A quasi-experimental
field study revealed more exaggerated reports of staircase steepness in
overweight than in healthy-weight participants in a situation where experimental
demand would be an implausible explanation for any differences. A longitudinal
follow-up study used dual X-ray absorptiometry to objectively measure
participants' body composition at the beginning and end of a weight-loss program
(N = 52). At baseline, higher levels of body fat were associated with steeper
explicit estimates of staircase steepness. At follow-up, changes in body fat were
associated with changes in estimated steepness such that a loss of fat mass co
occurred with shallower estimates. Discussion focuses on the malleability of
perceived steepness at an individual level and the implication of these findings
for the debate surrounding "embodied" models of perception. (PsycINFO Database
Record
PMID- 26414168
TI - Automaticity and primacy of auditory streaming: Concurrent subjective and
objective measures.
AB - Two experiments used subjective and objective measures to study the automaticity
and primacy of auditory streaming. Listeners heard sequences of "ABA-" triplets,
where "A" and "B" were tones of different frequencies and "-" was a silent gap.
Segregation was more frequently reported, and rhythmically deviant triplets less
well detected, for a greater between-tone frequency separation and later in the
sequence. In Experiment 1, performing a competing auditory task for the first
part of the sequence led to a reduction in subsequent streaming compared to when
the tones were attended throughout. This is consistent with focused attention
promoting streaming, and/or with attention switches resetting it. However, the
proportion of segregated reports increased more rapidly following a switch than
at the start of a sequence, indicating that some streaming occurred
automatically. Modeling ruled out a simple "covert attention" account of this
finding. Experiment 2 required listeners to perform subjective and objective
tasks concurrently. It revealed superior performance during integrated compared
to segregated reports, beyond that explained by the codependence of the two
measures on stimulus parameters. We argue that listeners have limited access to
low-level stimulus representations once perceptual organization has occurred, and
that subjective and objective streaming measures partly index the same processes.
PMID- 26414170
TI - Graphitic Carbon Conformal Coating of Mesoporous TiO2 Hollow Spheres for High
Performance Lithium Ion Battery Anodes.
AB - Rational design and controllable synthesis of TiO2 based materials with unique
microstructure, high reactivity, and excellent electrochemical performance for
lithium ion batteries are crucially desired. In this paper, we developed a
versatile route to synthesize hollow TiO2/graphitic carbon (H-TiO2/GC) spheres
with superior electrochemical performance. The as-prepared mesoporous H-TiO2/GC
hollow spheres present a high specific surface area (298 m(2) g(-1)), a high pore
volume (0.31 cm(3) g(-1)), a large pore size (~5 nm), well-defined hollow
structure (monodispersed size of 600 nm and inner diameter of ~400 nm, shell
thickness of 100 nm), and small nanocrystals of anatase TiO2 (~8 nm) conformably
encapsulated in ultrathin graphitic carbon layers. As a result, the H-TiO2/GC
hollow spheres achieve excellent electrochemical reactivity and stability as an
anode material for lithium ion batteries. A high specific capacity of 137 mAh g(
1) can be achieved up to 1000 cycles at a current density of 1 A g(-1) (5 C). We
believe that the mesoporous H-TiO2/GC hollow spheres are expected to be applied
as a high-performance electrode material for next generation lithium ion
batteries.
PMID- 26414169
TI - Higher Activation in CD4(+) T Cells But Similar Viral Control Among HIV/Hepatitis
C Virus-Coinfected Patients on a Simplification Monotherapy.
AB - The aim of this study was to assess whether hepatitis C virus (HCV) coinfection
would affect the clinical and immunological outcome of HIV-infected patients
following a simplification strategy. A prospective cohort of HIV-infected
patients starting a ritonavir boosted darunavir monotherapy (mtDRV/rtv) was
followed for 24 months. HCV infection was evaluated by HCV viremia and hepatic
fibrosis. Immune activation was studied as HLA-DR CD38 coexpression on CD4(+) and
CD8(+) T cells and also the quantification of plasma sCD14 levels. Microbial
translocation was studied by the plasma levels of 16S rDNA and lipopolysaccharide
(LPS). A total of 150 HIV-infected patients were enrolled in this study,
including 46 individuals also infected with HCV (30.6%). HIV/HCV coinfection did
not decrease mtDRV/rtv efficacy, since similar rates of HIV-1 intermittent
viremia (HCV: 26.6% vs. no-HCV: 34.7%) and episodes of virological failure (HCV:
22.2% vs. no-HCV: 11.2%, p-value = 0.381) were found. No major differences were
found between both groups at baseline, although higher HLA-DR(+)CD38(+)CD4(+) T
cell counts were found in the coinfected group (HCV: 6.65% vs. no-HCV: 4.55%, p
value = 0.032); this difference was maintained in the 24 months of follow-up.
After the 24-month follow-up, both groups, HIV-monoinfected patients and HIV/HCV
coinfected patients, presented similar immune activation and microbial
translocation profiles. In conclusion, the use of a simplified mtDRV/rtv strategy
compromises neither HIV nor HCV viremic control in coinfected patients, although
a higher immune activation of CD4(+) T cells was found.
PMID- 26414172
TI - Activation of FGF1B Promoter and FGF1 Are Involved in Cardiogenesis Through the
Signaling of PKC, but Not MAPK.
AB - Heart disease is the leading cause of human death in the 21st century. Heart
transplantation is a promising way to treat this. Because donor resources are
limited, cell-based therapy has been developed as an alternative. Therefore,
genes that trigger cardiogenesis could have potential in the treatment of heart
disease. Fibroblast growth factor 1 (FGF1) is reported to stimulate cardiomyocyte
proliferation under conditions of myocardial infarction, but little is known
about its function during cardiac differentiation. In this study, we established
an in vitro cardiogenesis model through a reliable chemical induction protocol to
determine whether FGF1 and its gene expression are involved in cardiogenesis.
Oxytocin, not only a well-known hormone but also a cardiac differentiation
inducer, was used in a mouse embryonic stem cell line, E14Tg2a, to achieve
cardiac differentiation. After differentiation, beating cell clusters appeared
and the expression of FGF1B mRNA was upregulated in the late differentiation
stage (differentiation days 8-14). Interestingly, FGF1B expression patterns
during cardiac differentiation were similar to those of a mature cardiomyocyte
marker, troponin T2, cardiac. The blockage of FGF1-FGF receptor (FGFR) signaling
reduced not only the appearance of beating cluster formation but also the
expression levels of cardiomyocyte-associated genes. Moreover, by investigating
FGF1 downstream signaling cascades, we observed that the efficiency of beating
cluster formation was mainly regulated through the FGF1-FGFR-PKC signaling axis.
Taken together, we provide evidence to support that FGF1 could regulate
cardiogenesis primarily through the protein kinase C signaling, but not through
the mitogen-activated protein kinase signaling, pathway.
PMID- 26414173
TI - Surgical Treatment of Cor Triatriatum Sinister in a Cat Under Cardiopulmonary
Bypass.
AB - OBJECTIVE: To report the surgical repair of cor triatriatum sinister (CTS)
incorporating heart-beating cardiopulmonary bypass (CPB) in a cat. STUDY DESIGN:
Clinical case report. ANIMAL: Fourteen-month-old, 5.9-kg male castrated Maine
Coon cat. MATERIALS AND METHODS: The cat had a 3 month history of inappetance,
weight loss, and recurrent pulmonary edema. CTS with severe systolic pulmonary
arterial (SPA) hypertension (124 mm Hg) was diagnosed by 2D echocardiography,
color flow and continuous wave Doppler modes, and left atrial and pulmonary
angiography. Surgery was performed through a left intercostal thoracotomy. CPB
was initiated and the heart was kept beating. The left atrial appendage was
opened and the intra-atrial membrane was excised. RESULTS: After 48 hours, the
cat was doing well. Reduced SPA pressure (52 mm Hg) with decreased right heart
enlargement was observed on ultrasound examination and the cat was discharged 6
days after surgery with oral antibiotics for 10 days, aspirin, and furosemide.
Four months after surgery, the cat presented with increased activity and weight
gain and was completely asymptomatic. Transthoracic echocardiography showed a
marked improvement of all echo-Doppler variables with disappearance of SPA
hypertension (24 mm Hg). Four years after surgery, the cat was still doing well
with no recurrence of clinical signs despite the lack of medical treatment.
CONCLUSION: CTS in the cat may be successfully treated by surgery facilitated by
use of CPB leading to early and long-term substantial improvement in clinical
status and cardiac function. CTS can safely be repaired under CPB in cats.
PMID- 26414174
TI - Environmental Influences on Endothelial to Mesenchymal Transition in Developing
Implanted Cardiovascular Tissue-Engineered Grafts.
AB - Tissue-engineered grafts for cardiovascular structures experience biochemical
stimuli and mechanical forces that influence tissue development after
implantation such as the immunological response, oxidative stress, hemodynamic
shear stress, and mechanical strain. Endothelial cells are a cell source of major
interest in vascular tissue engineering because of their ability to form a
luminal antithrombotic monolayer. In addition, through their ability to undergo
endothelial to mesenchymal transition (EndMT), endothelial cells may yield a cell
type capable of increased production and remodeling of the extracellular matrix
(ECM). ECM is of major importance to the mechanical function of all
cardiovascular structures. Tissue engineering approaches may employ EndMT to
recapitulate, in part, the embryonic development of cardiovascular structures.
Improved understanding of how the environment of an implanted graft could
influence EndMT in endothelial cells may lead to novel tissue engineering
strategies. This review presents an overview of biochemical and mechanical
stimuli capable of influencing EndMT, discusses the influence of these stimuli as
found in the direct environment of cardiovascular grafts, and discusses
approaches to employ EndMT in tissue-engineered constructs.
PMID- 26414175
TI - Facilitators and Barriers to Spinal Cord Injury Clinical Trial Participation:
Multi-National Perspective of People Living with Spinal Cord Injury.
AB - These are exciting times for the translation of promising interventions for
spinal cord injury (SCI) into testing with clinical trials. These interventions
include acute surgical decompression, neuroprotection, neural repair, cell
replacement, activity-based rehabilitation, and medical devices, including
devices requiring surgical implantation. By nature, clinical trials can have
strict inclusion and exclusion criteria, which narrow down the pool of potential
participants. Meeting enrollment numbers for properly powered trials is a
daunting task. Therefore, it is important that trials are designed in a manner
that facilitates participation. The purpose of this research study was to learn
more about the factors that encourage or interfere with the decision to
participate in clinical trials from the perspective of people living with SCI. A
multi-national survey was conducted, primarily online, in which 802 participants
with SCI ranked 32 factors as facilitators or barriers, using a Likert-type
scale. There were 13 universal facilitators, five universal barriers, and three
universally neutral factors. The number one facilitator was possible improvement
in functionality and the number one barrier was possible decline in functionality
-as may be expected. However, many unexpected facilitators and barriers were
identified. There also were certain factors that were strong barriers or
facilitators to certain sub-groups of people living with SCI. All of these
factors should be taken into careful consideration when designing clinical trials
so as to promote enrollment and enable adherence to different protocols.
PMID- 26414177
TI - Influence of C-Trap Ion Accumulation Time on the Detectability of Analytes in IR
MALDESI MSI.
AB - Laser desorption followed by post electrospray ionization requires synchronized
timing of the key events (sample desorption/ionization, mass spectrometry
analysis, and sample translation) necessary to conduct mass spectrometry imaging
(MSI) with adequate analyte sensitivity. In infrared matrix-assisted laser
desorption electrospray ionization (IR-MALDESI) MSI analyses, two laser pulses
are used for analysis at each volumetric element, or voxel, of a biological
sample and ion accumulation in the C-trap exceeding 100 ms is necessary to
capture all sample-associated ions using an infrared laser with a 20 Hz
repetition rate. When coupled to an Orbitrap-based mass spectrometer like the Q
Exactive Plus, this time window for ion accumulation exceeds dynamically
controlled trapping of samples with comparable ion flux by Automatic Gain Control
(AGC), which cannot be used during MSI analysis. In this work, a next-generation
IR-MALDESI source has been designed and constructed that incorporates a mid
infrared OPO laser capable of operating at 100 Hz and allows requisite C-trap
inject time during MSI to be reduced to 30 ms. Analyte detectability of the next
generation IR-MALDESI integrated source has been evaluated as a function of laser
repetition rate (100-20 Hz) with corresponding C-trap ion accumulation times (30
110 ms) in both untargeted and targeted analysis of biological samples. Reducing
the C-trap ion accumulation time resulted in increased ion abundance by up to 3
orders of magnitude for analytes ranging from xenobiotics to endogenous lipids,
and facilitated the reduction of voxel-to-voxel variability by more than 3-fold.
PMID- 26414178
TI - The Complete Genome Phylogeny of Geographically Distinct Dengue Virus Serotype 2
Isolates (1944-2013) Supports Further Groupings within the Cosmopolitan Genotype.
AB - Dengue virus serotype 2 (DENV-2) isolates have been implicated in deadly
outbreaks of dengue fever (DF) and dengue hemorrhagic fever (DHF) in several
regions of the world. Phylogenetic analysis of DENV-2 isolates collected from
particular countries has been performed using partial or individual genes but
only a few studies have examined complete whole-genome sequences collected
worldwide. Herein, 50 complete genome sequences of DENV-2 isolates, reported over
the past 70 years from 19 different countries, were downloaded from GenBank.
Phylogenetic analysis was conducted and evolutionary distances of the 50 DENV-2
isolates were determined using maximum likelihood (ML) trees or Bayesian
phylogenetic analysis created from complete genome nucleotide (nt) and amino acid
(aa) sequences or individual gene sequences. The results showed that all DENV-2
isolates fell into seven main groups containing five previously defined
genotypes. A Cosmopolitan genotype showed further division into three groups (C
I, C-II, and C-III) with the C-I group containing two subgroups (C-IA and C-IB).
Comparison of the aa sequences showed specific mutations among the various groups
of DENV-2 isolates. A maximum number of aa mutations was observed in the NS5
gene, followed by the NS2A, NS3 and NS1 genes, while the smallest number of aa
substitutions was recorded in the capsid gene, followed by the PrM/M, NS4A, and
NS4B genes. Maximum evolutionary distances were found in the NS2A gene, followed
by the NS4A and NS4B genes. Based on these results, we propose that genotyping of
DENV-2 isolates in future studies should be performed on entire genome sequences
in order to gain a complete understanding of the evolution of various isolates
reported from different geographical locations around the world.
PMID- 26414176
TI - Development of Preliminary Remission Criteria for Gout Using Delphi and 1000Minds
Consensus Exercises.
AB - OBJECTIVE: To establish consensus for potential remission criteria to use in
clinical trials of gout. METHODS: Experts (n = 88) in gout from multiple
countries were invited to participate in a web-based questionnaire study. Three
rounds of Delphi consensus exercises were conducted using SurveyMonkey, followed
by a discrete-choice experiment using 1000Minds software. The exercises focused
on identifying domains, definitions for each domain, and the timeframe over which
remission should be defined. RESULTS: There were 49 respondents (56% response) to
the initial survey, with subsequent response rates ranging from 57% to 90%.
Consensus was reached for the inclusion of serum urate (98% agreement), flares
(96%), tophi (92%), pain (83%), and patient global assessment of disease activity
(93%) as measurement domains in remission criteria. Consensus was also reached
for domain definitions, including serum urate (<0.36 mm), pain (<2 on a 10-point
scale), and patient global assessment (<2 on a 10-point scale), all of which
should be measured at least twice over a set time interval. Consensus was not
achieved in the Delphi exercise for the timeframe for remission, with equal
responses for 6 months (51%) and 1 year (49%). In the discrete-choice experiment,
there was a preference towards 12 months as a timeframe for remission.
CONCLUSION: These consensus exercises have identified domains and provisional
definitions for gout remission criteria. Based on the results of these exercises,
preliminary remission criteria are proposed with domains of serum urate, acute
flares, tophus, pain, and patient global assessment. These preliminary criteria
now require testing in clinical data sets.
PMID- 26414180
TI - An overview of imaging techniques for liver metastases management.
AB - Evaluation of liver metastases is one of the most common indications for liver
imaging. Imaging plays a key role in the of assessment liver metastases. A
variety of imaging techniques, including ultrasonography, computed tomography,
MRI and PET combined with CT scan are available for diagnosis, planning
treatment, and follow-up treatment response. In this paper, the authors present
the role of imaging for the assessment of liver metastases and the contribution
of each of the different imaging techniques for their evaluation and management.
Following recent developments in the field of oncology, the authors also present
the importance of imaging for the assessment of liver metastases response to
therapy. Finally, future perspectives on imaging of liver metastases are
presented.
PMID- 26414179
TI - Redesigning Recombinase Specificity for Safe Harbor Sites in the Human Genome.
AB - Site-specific recombinases (SSRs) are valuable tools for genetic engineering due
to their ability to manipulate DNA in a highly specific manner. Engineered zinc
finger and TAL effector recombinases, in particular, are two classes of SSRs
composed of custom-designed DNA-binding domains fused to a catalytic domain
derived from the resolvase/invertase family of serine recombinases. While TAL
effector and zinc-finger proteins can be assembled to recognize a wide range of
possible DNA sequences, recombinase catalytic specificity has been constrained by
inherent base requirements present within each enzyme. In order to further expand
the targeted recombinase repertoire, we used a genetic screen to isolate enhanced
mutants of the Bin and Tn21 recombinases that recognize target sites outside the
scope of other engineered recombinases. We determined the specific base
requirements for recombination by these enzymes and demonstrate their potential
for genome engineering by selecting for variants capable of specifically
recombining target sites present in the human CCR5 gene and the AAVS1 safe harbor
locus. Taken together, these findings demonstrate that complementing functional
characterization with protein engineering is a potentially powerful approach for
generating recombinases with expanded targeting capabilities.
PMID- 26414181
TI - Reconstructing the fractal dimension of granular aggregates from light intensity
spectra.
AB - There has been growing interest in using the fractal dimension to study the
hierarchical structures of soft materials after realising that fractality is an
important property of natural and engineered materials. This work presents a
method to quantify the internal architecture and the space-filling capacity of
granular fractal aggregates by reconstructing the three-dimensional capacity
dimension from their two-dimensional optical projections. Use is made of the
light intensity of the two-dimensional aggregate images to describe the aggregate
surface asperities (quantified by the perimeter-based fractal dimension) and the
internal architecture (quantified by the capacity dimension) within a
mathematical framework. This method was tested on control aggregates of diffusion
limited (DLA), cluster-cluster (CCA) and self-correlated (SCA) types,
stereolithographically-fabricated aggregates, and experimentally-acquired natural
sedimentary aggregates. Statistics of the reconstructed capacity dimension
featured correlation coefficients R >= 98%, residuals NRMSE <= 10% and percent
errors PE <= 4% as compared to controls, and improved earlier approaches by up to
50%.
PMID- 26414182
TI - An Approach to Improve the Performance of PM Forecasters.
AB - The particulate matter (PM) concentration has been one of the most relevant
environmental concerns in recent decades due to its prejudicial effects on living
beings and the earth's atmosphere. High PM concentration affects the human health
in several ways leading to short and long term diseases. Thus, forecasting
systems have been developed to support decisions of the organizations and
governments to alert the population. Forecasting systems based on Artificial
Neural Networks (ANNs) have been highlighted in the literature due to their
performances. In general, three ANN-based approaches have been found for this
task: ANN trained via learning algorithms, hybrid systems that combine search
algorithms with ANNs, and hybrid systems that combine ANN with other forecasters.
Independent of the approach, it is common to suppose that the residuals (error
series), obtained from the difference between actual series and forecasting, have
a white noise behavior. However, it is possible that this assumption is infringed
due to: misspecification of the forecasting model, complexity of the time series
or temporal patterns of the phenomenon not captured by the forecaster. This paper
proposes an approach to improve the performance of PM forecasters from residuals
modeling. The approach analyzes the remaining residuals recursively in search of
temporal patterns. At each iteration, if there are temporal patterns in the
residuals, the approach generates the forecasting of the residuals in order to
improve the forecasting of the PM time series. The proposed approach can be used
with either only one forecaster or by combining two or more forecasting models.
In this study, the approach is used to improve the performance of a hybrid system
(HS) composed by genetic algorithm (GA) and ANN from residuals modeling performed
by two methods, namely, ANN and own hybrid system. Experiments were performed for
PM2.5 and PM10 concentration series in Kallio and Vallila stations in Helsinki
and evaluated from six metrics. Experimental results show that the proposed
approach improves the accuracy of the forecasting method in terms of fitness
function for all cases, when compared with the method without correction. The
correction via HS obtained a superior performance, reaching the best results in
terms of fitness function and in five out of six metrics. These results also were
found when a sensitivity analysis was performed varying the proportions of the
sets of training, validation and test. The proposed approach reached consistent
results when compared with the forecasting method without correction, showing
that it can be an interesting tool for correction of PM forecasters.
PMID- 26414183
TI - Emergence of OXA-48-Producing Klebsiella pneumoniae in Taiwan.
AB - The isolation of OXA-48-producing Enterobacteriaceae has increased dramatically
in Mediterranean countries in the past 10 years, and has recently emerged in
Asia. Between January 2012 and May 2014, a total of 760 carbapenem non
susceptible Klebsiella pneumoniae (CnSKP) isolates were collected during a Taiwan
national surveillance. Carbapenemases were detected in 210 CnSKP isolates
(27.6%), including 162 KPC-2 (n = 1), KPC-3, KPC-17, and NDM-1 (n = 1 each), OXA
48 (n = 4), IMP-8 (n = 18), and VIM-1 (n = 24). The four blaOXA-48 CnSKP isolates
were detected in late 2013. Herein we report the emergence OXA-48-producing K.
pneumoniae isolates in Taiwan. PFGE analysis revealed that the four isolates
belonged to three different pulsotypes. Three isolates harboured blaCTX-M genes
and belonged to MLST type ST11. In addition, the plasmids belonged to the
incompatibility group, IncA/C. One isolate belonged to ST116 and the plasmid
incompatibility group was non-typeable. The sequence upstream of the blaOXA-48
gene in all four isolates was identical to pKPOXA-48N1, a blaOXA-48-carrying
plasmid. This is the first report of OXA-48-producing Enterobacteriaceae in
Taiwan and the second report to identify blaOXA-48 on an IncA/C plasmid in K.
pneumoniae. Given that three isolates belong to the same pandemic clone (ST11)
and possess the IncA/C plasmid and similar plasmid digestion profile that
indicated the role of clonal spread or plasmid for dissemination of blaOXA-48
gene, the emergence of OXA-48-producing K. pneumoniae in Taiwan is of great
concern.
PMID- 26414185
TI - Platelet transfusion and respecting patient D type.
AB - PURPOSE OF REVIEW: Current guidance allows transfusing D-mismatched platelets to
D negative recipients when necessitated by logistic constraints. Although the D
antigen is not expressed on the platelet membrane, platelet concentrates are
still labeled by their D antigen status because the platelet concentrates contain
a small quantity of red blood cells. D matching is currently recommended to
prevent D alloimmunization based on frequencies of D alloimmunization after
transfusing platelet concentrates obtained from whole blood collections of up to
18.7%. RECENT FINDINGS: The content of red blood cells is higher in pooled
platelet concentrates prepared from whole blood collections (range: 0.036-0.59
ml) than in platelet concentrates obtained from apheresis devices (range: 0.00017
0.009 ml). Large retrospective studies with long follow-up suggest that it is not
possible to rule out a secondary immunization in D negative patients who
developed an alloanti-D within 4 weeks after receiving the first D-mismatched
platelet transfusion, and the frequency of D alloimmunization after D-mismatched
platelet transfusions ranges between 0 and 7.1%. SUMMARY: Based on the reported
frequencies of D alloimmunization and data from some recent large studies, we
recommend administering Rh Immune Globulin, if D-mismatched platelet concentrates
prepared from whole blood collections are transfused to D negative females of
childbearing potential.
PMID- 26414186
TI - Neutrophil/granulocyte transfusions collected from G-CSF + dexamethasone
stimulated donors.
AB - PURPOSE OF REVIEW: The purpose of this review is to report a recently completed
multicenter randomized controlled trial of neutrophil/granulocyte transfusions
collected from G-CSF + dexamethasone donors to treat neutropenic infections in
oncology and transplant patients, within the context of other historic and
current clinical trials.The multicenter trial (RING Study) was funded by the
NHLBI transfusion medicine/hemostasis clinical trials network. RECENT FINDINGS:
There was no significant benefit of therapeutic neutrophil/granulocyte
transfusions versus antibiotics per intention to treat analysis, but 32% of
patients received substandard neutrophil doses. Separate analysis suggested
patients given a higher neutrophil doses had better outcomes. SUMMARY: Efficacy
of 'high-dose' therapeutic neutrophil/granulocyte transfusions remains unproven,
but promising.
PMID- 26414184
TI - The Viral Mimetic Polyinosinic:Polycytidylic Acid Alters the Growth
Characteristics of Small Intestinal and Colonic Crypt Cultures.
AB - BACKGROUND & AIMS: The intestinal epithelium is the first line of defense against
enteric pathogens. We investigated the response of small intestinal and colonic
crypt cultures to a panel of toll-like receptor ligands to assess the impact of
microbial pattern recognition on epithelial growth. METHODS: Primary murine
jejunal enteroids and colonoids were cultured with lipopeptide Pam3CSK4,
lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (Poly I:C) for 4 to 6
days. Surface area, budding and survival were assessed. Proliferation and numbers
of lysozyme positive cells were quantified by flow cytometry. Gene expression was
assessed by Nanostring and qRT-PCR. RESULTS: Exposure to Pam3CSK4 and LPS had
minimal impact on either enteroids or colonoids. In contrast, Poly I:C increased
the surface area of enteroids, while colonoids demonstrated decreased budding.
Survival was decreased by Poly I:C in enteroids but not in colonoids. Both
enteroids and colonoids exhibited upregulated gene expression of chemokines, but
these were increased in magnitude in enteroids. Decreases in gene expression
associated with epithelial differentiation and lysozyme positive cells were more
apparent in enteroids than in colonoids. Baseline gene expression between
enteroids and colonoids differed markedly in levels of stem cell and inflammatory
markers. The changes in morphology induced by Poly I:C were mediated by the toll
like receptor adaptor molecule 1 (Ticam1) in enteroids but not in colonoids.
CONCLUSIONS: Poly I:C alters the molecular program of epithelial cells and shifts
from absorption and digestion towards defense and inflammation. Diversity of
responses to microbial patterns in enteroids and colonoids may underlie
differences in susceptibility to infection along the intestinal tract.
PMID- 26414189
TI - Single nucleotide polymorphisms in TP53 but not KRAS or MDM2 are predictive of
clinical outcome in multiple myeloma treated with high-dose melphalan and
autologous stem cell support.
PMID- 26414190
TI - Social power and recognition of emotional prosody: High power is associated with
lower recognition accuracy than low power.
AB - Listeners have to pay close attention to a speaker's tone of voice (prosody)
during daily conversations. This is particularly important when trying to infer
the emotional state of the speaker. Although a growing body of research has
explored how emotions are processed from speech in general, little is known about
how psychosocial factors such as social power can shape the perception of vocal
emotional attributes. Thus, the present studies explored how social power affects
emotional prosody recognition. In a correlational study (Study 1) and an
experimental study (Study 2), we show that high power is associated with lower
accuracy in emotional prosody recognition than low power. These results, for the
first time, suggest that individuals experiencing high or low power perceive
emotional tone of voice differently.
PMID- 26414191
TI - The impact of affective contexts on working memory capacity in healthy
populations and in individuals with PTSD.
AB - Individual differences in working memory capacity (WMC) strongly predict
variations in real-world cognitive functioning. However, little is known about
how WMC is influenced by the ubiquitously present affective information in our
everyday environments. Here, we present a series of 3 experiments investigating a
novel WMC paradigm performed in affective (vs. neutral) contexts. The paradigm
requires simultaneous performance of a visuospatial search and a verbal storage
task. These tasks are performed in the presence of either neutral or negative
emotional distractor images. Experiments 1 and 2 confirmed our prediction that
WMC would be reduced in the context of emotional compared with neutral
distractors in student and community samples. Experiment 3 extended these
findings to a clinical sample. WMC in motor vehicle accident survivors with a
history of posttraumatic stress disorder (PTSD) was selectively reduced in the
presence of trauma-related emotional distraction compared with survivors without
a history of PTSD. Implications of these findings for affective cognitive science
are discussed.
PMID- 26414193
TI - Metagenomic insights into the dynamics of microbial communities in food.
AB - Metagenomics has proven to be a powerful tool in exploring a large diversity of
natural environments such as air, soil, water, and plants, as well as various
human microbiota (e.g. digestive tract, lungs, skin). DNA sequencing techniques
are becoming increasingly popular and less and less expensive. Given that high
throughput DNA sequencing approaches have only recently started to be used to
decipher food microbial ecosystems, there is a significant growth potential for
such technologies in the field of food microbiology. The aim of this review is to
present a survey of recent food investigations via metagenomics and to illustrate
how this approach can be a valuable tool in the better characterization of foods
and their transformation, storage and safety. Traditional food in particular has
been thoroughly explored by global approaches in order to provide information on
multi-species and multi-organism communities.
PMID- 26414192
TI - A New Acute Impact-Compression Lumbar Spinal Cord Injury Model in the Rodent.
AB - Traumatic injury to the lumbar spinal cord results in complex central and
peripheral nervous tissue damage causing significant neurobehavioral deficits and
personal/social adversity. Although lumbar cord injuries are common in humans,
there are few clinically relevant models of lumbar spinal cord injury (SCI). This
article describes a novel lumbar SCI model in the rat. The effects of moderate
(20 g), moderate-to-severe (26 g) and severe (35 g, and 56 g) clip impact
compression injuries at the lumbar spinal cord level L1-L2 (vertebral level T11
T12) were assessed using several neurobehavioral, neuroanatomical, and
electrophysiological outcome measures. Lesions were generated after meticulous
anatomical landmarking using microCT, followed by laminectomy and extradural
inclusion of central and radicular elements to generate a traumatic SCI.
Clinically relevant outcomes, such as MR and ultrasound imaging, were paired with
robust morphometry. Analysis of the lesional tissue demonstrated that pronounced
tissue loss and cavitation occur throughout the acute to chronic phases of
injury. Behavioral testing revealed significant deficits in locomotion, with no
evidence of hindlimb weight-bearing or hindlimb-forelimb coordination in any
injured group. Evaluation of sensory outcomes revealed highly pathological
alterations including mechanical allodynia and thermal hyperalgesia indicated by
increasing avoidance responses and decreasing latency in the tail-flick test.
Deficits in spinal tracts were confirmed by electrophysiology showing increased
latency and decreased amplitude of both sensory and motor evoked potentials
(SEP/MEP), and increased plantar H-reflex indicating an increase in motor neuron
excitability. This is a comprehensive lumbar SCI model and should be useful for
evaluation of translationally oriented pre-clinical therapies.
PMID- 26414195
TI - Optical rectennas: Nanotubes circumvent trade-offs.
PMID- 26414194
TI - Infrared rectification in a nanoantenna-coupled metal-oxide-semiconductor tunnel
diode.
AB - Direct rectification of electromagnetic radiation is a well-established method
for wireless power conversion in the microwave region of the spectrum, for which
conversion efficiencies in excess of 84% have been demonstrated. Scaling to the
infrared or optical part of the spectrum requires ultrafast rectification that
can only be obtained by direct tunnelling. Many research groups have looked to
plasmonics to overcome antenna-scaling limits and to increase the confinement.
Recently, surface plasmons on heavily doped Si surfaces were investigated as a
way of extending surface-mode confinement to the thermal infrared region. Here we
combine a nanostructured metallic surface with a heavily doped Si infrared
reflective ground plane designed to confine infrared radiation in an active
electronic direct-conversion device. The interplay of strong infrared photon
phonon coupling and electromagnetic confinement in nanoscale devices is
demonstrated to have a large impact on ultrafast electronic tunnelling in metal
oxide-semiconductor (MOS) structures. Infrared dispersion of SiO2 near a
longitudinal optical (LO) phonon mode gives large transverse-field confinement in
a nanometre-scale oxide-tunnel gap as the wavelength-dependent permittivity
changes from 1 to 0, which leads to enhanced electromagnetic fields at material
interfaces and a rectified displacement current that provides a direct conversion
of infrared radiation into electric current. The spectral and electrical
signatures of the nanoantenna-coupled tunnel diodes are examined under broadband
blackbody and quantum-cascade laser (QCL) illumination. In the region near the LO
phonon resonance, we obtained a measured photoresponsivity of 2.7 mA W(-1) cm(-2)
at -0.1 V.
PMID- 26414196
TI - Surface imaging beyond the diffraction limit with optically trapped spheres.
AB - Optical traps play an increasing role in the bionanosciences because of their
ability to apply forces flexibly on tiny structures in fluid environments.
Combined with particle-tracking techniques, they allow the sensing of miniscule
forces exerted on these structures. Similar to atomic force microscopy (AFM), but
much more sensitive, an optically trapped probe can be scanned across a
structured surface to measure the height profile from the displacements of the
probe. Here we demonstrate that, by the combination of a time-shared twin-optical
trap and nanometre-precise three-dimensional interferometric particle tracking,
both reliable height profiling and surface imaging are possible with a spatial
resolution below the diffraction limit. The technique exploits the high-energy
thermal position fluctuations of the trapped probe, and leads to a sampling of
the surface 5,000 times softer than in AFM. The measured height and force
profiles from test structures and Helicobacter cells illustrate the potential to
uncover specific properties of hard and soft surfaces.
PMID- 26414198
TI - A carbon nanotube optical rectenna.
AB - An optical rectenna--a device that directly converts free-propagating
electromagnetic waves at optical frequencies to direct current--was first
proposed over 40 years ago, yet this concept has not been demonstrated
experimentally due to fabrication challenges at the nanoscale. Realizing an
optical rectenna requires that an antenna be coupled to a diode that operates on
the order of 1 PHz (switching speed on the order of 1 fs). Diodes operating at
these frequencies are feasible if their capacitance is on the order of a few
attofarads, but they remain extremely difficult to fabricate and to reliably
couple to a nanoscale antenna. Here we demonstrate an optical rectenna by
engineering metal-insulator-metal tunnel diodes, with a junction capacitance of
~2 aF, at the tip of vertically aligned multiwalled carbon nanotubes (~10 nm in
diameter), which act as the antenna. Upon irradiation with visible and infrared
light, we measure a d.c. open-circuit voltage and a short-circuit current that
appear to be due to a rectification process (we account for a very small but
quantifiable contribution from thermal effects). In contrast to recent reports of
photodetection based on hot electron decay in a plasmonic nanoscale antenna, a
coherent optical antenna field appears to be rectified directly in our devices,
consistent with rectenna theory. Finally, power rectification is observed under
simulated solar illumination, and there is no detectable change in diode
performance after numerous current-voltage scans between 5 and 77 degrees C,
indicating a potential for robust operation.
PMID- 26414197
TI - Nanoscale cation motion in TaO(x), HfO(x) and TiO(x) memristive systems.
AB - A detailed understanding of the resistive switching mechanisms that operate in
redox-based resistive random-access memories (ReRAM) is key to controlling these
memristive devices and formulating appropriate design rules. Based on distinct
fundamental switching mechanisms, two types of ReRAM have emerged:
electrochemical metallization memories, in which the mobile species is thought to
be metal cations, and valence change memories, in which the mobile species is
thought to be oxygen anions (or positively charged oxygen vacancies). Here we
show, using scanning tunnelling microscopy and supported by potentiodynamic
current-voltage measurements, that in three typical valence change memory
materials (TaO(x), HfO(x) and TiO(x)) the host metal cations are mobile in films
of 2 nm thickness. The cations can form metallic filaments and participate in the
resistive switching process, illustrating that there is a bridge between the
electrochemical metallization mechanism and the valence change mechanism.
Reset/Set operations are, we suggest, driven by oxidation (passivation) and
reduction reactions. For the Ta/Ta2O5 system, a rutile-type TaO2 film is believed
to mediate switching, and we show that devices can be switched from a valence
change mode to an electrochemical metallization mode by introducing an
intermediate layer of amorphous carbon.
PMID- 26414199
TI - HDAC4 stabilizes SIRT1 via sumoylation SIRT1 to delay cellular senescence.
AB - The nicotinamide adenine dinucleotide-dependent protein deacetylase silent
information regulator 2 (Sir2) regulates cellular lifespan in several organisms.
Histone deacetylase 4 (HDAC4) belongs to the class IIa group of HDACs; this class
of HDACs is composed of proteins that are important regulators of gene expression
that control pleiotropic cellular functions. However, the role of HDAC4 in
cellular senescence is still unknown. This study shows that the expression
patterns of HDAC4 and Sirtuin 1 (SIRT1; the mammalian homolog of Sir2) are
positively correlated during cellular senescence. Moreover, the overexpression of
HDAC4 delays senescence, whereas the knockdown of HDAC4 leads to premature
senescence in human fibroblasts. Furthermore, it is demonstrated that HDAC4
increases endogenous SIRT1 expression by enhancing its sumoylation modification
levels, thereby stabilizing its protein levels. This study, therefore, provides a
new molecular mechanism for the regulation of cellular senescence.
PMID- 26414200
TI - Contrasting Solid-State Fluorescence of Diynes with Small and Large Aryl
Substituents: Crystal Packing Dependence and Stimuli-Responsive Fluorescence
Switching.
AB - There has been a significant current interest in solid state luminescence of
organic molecules and their stimuli responsive fluorescence switching behavior.
Although small organic derivatives with olefinic, acetylenic, phenylenevinylenic,
phenyleneethynylenic spacers are widely documented as solid state emitters in the
literature, the solid state photophysics of organic derivatives with "butadiyne"
spacer still remains unexplored. We provide detailed investigation on the solid
state fluorescence properties of a series of butadiynyl fluorophores. Replacement
of a phenyl ring, which is at periphery of the butadiyne bridge, with a large
moiety such as pyrenyl group furnishes contrasting emissions in the solid state.
While the butadiyne bridged phenyl derivatives show a blue shift of emission
maxima in the solid powder with respect to monomer spectra in solution state, the
butadiyne bridged pyrenyl derivatives exhibit a red shift in the solid state. The
blue shift of the emission maxima of the butadiyne bridged phenyl derivatives in
the solid powder is attributed to allowed excitonic transition in aggregates with
nearly parallel transition dipoles. On the other hand, formation of pyrenyl
excimer accounts for the red shift of the butadiyne bridged pyrenyl derivatives
in the solid powder. In addition to that, the solid state fluorescence of the
pyrenyl analogues is reversibly switched between two aggregate forms through
external heating and rubbing stimuli.
PMID- 26414201
TI - Enantioselective Synthesis of a Furan Lignan (+)-Sylvone.
AB - A synthesis of natural tetrahydrofuran lignan (+)-sylvone is achieved starting
from methyl allenoate in 5 steps. The synthesis begins from an enantioselective
aldol reaction of methyl allenoate with 3,4-dimethoxybenzaldehyde to afford alpha
addition aldol adduct. Key steps for the synthesis of sylvone include an
oxacyclization of the alpha-hydroxy allenyl adduct followed by a Michael addition
of a 1,3-dithiane derivative to establish a sylvone skeleton with suitable
stereoselections.
PMID- 26414202
TI - Functional electrical stimulation for the upper limb in tetraplegic spinal cord
injury: a systematic review.
AB - Technological advances have helped to improve functional ability in spinal cord
injury survivors. The aim of this study is to systematically review the evidence
for functional electrical stimulation (FES) on functional tasks involving the
upper limb in people with spinal cord injuries. The authors systematically
searched from September 2009 to September 2014 in relevant databases using a
combination of keywords covering spinal cord injury and FES. Studies were
selected using pre-determined criteria. The search yielded 144 studies. Only five
studies met the inclusion criteria. All five reported improvements immediately
and at follow-up in functional ability as a result of FES or FES combined with
conventional therapy. There is some preliminary evidence that FES may reduce
disability due to upper limb-related activity limitations in tetraplegic spinal
cord injury. Further work needs to examine the role of FES in more detail and in
combination with other treatments.
PMID- 26414203
TI - Patterns of fetal lung growth in fetuses with isolated left-sided congenital
diaphragmatic hernia.
AB - OBJECTIVE: To evaluate right lung growth pattern in fetuses with isolated left
sided congenital diaphragmatic hernia (iL-CDH) and to analyze the pattern
according to postnatal outcome. METHODS: Lung-to-head ratio (LHR) and observed-to
expected LHR (O/E LHR) were obtained in 58 cases. Correlation and regression
analysis for the total number of measurements, general linear models for those
cases with a least three serial measurements and linear mixed effect models were
used to analyze the influence of gestational age on the right lung size. Cases
expectantly managed and those with fetal endoscopic tracheal occlusion were
analyzed separately. RESULTS: LHR, but not O/E LHR, increased significantly with
gestational age (GA) (r = 0.43, p = 0.003 and r = -0.13, p = 0.30, respectively).
According to neonatal mortality, in those fetuses that died, LHR remained
unchanged and O/E LHR decreased significantly with GA (r = 0.07, p = 0.65 and r =
-0.37, p = 0.02, respectively). In those cases with at least three serial
measurements, the same two patterns were found. Similarly, in cases with
expectant management, surviving fetuses showed a significantly higher weekly
increase in LHR (p = 0.01) and a trend to a lower weekly decrease in O/E LHR (p =
0.17) than in those that died. CONCLUSIONS: Patterns of right lung growth in iL
CDH differ according to postnatal survival. Serial measurements, but not a single
one, might increase the prediction of neonatal death.
PMID- 26414204
TI - Understanding sibling influence on adolescents' alcohol use: Social and cognitive
pathways.
AB - Research indicates that older siblings uniquely influence their younger brothers'
and sisters' substance use behaviors during adolescence; however, the underlying
mechanisms of socialization are rarely examined. The present study investigated
whether social and/or cognitive pathways mediated the association between
adolescent siblings' alcohol use and whether these pathways were moderated by the
gender composition of the sibling dyad. Participants included one parent and two
adolescent siblings (M age=14.52 and 17.17years) from 326 families. Data were
collected via telephone interviews. Path analysis demonstrated that the
association between older and younger siblings' alcohol use was mediated via
social and cognitive pathways. Specifically, older siblings' drinking was
positively related to the frequency of siblings' co-use as well as more positive
expectations about alcohol, which in turn were positively associated with younger
siblings' alcohol use. Identifying the ways in which siblings influence each
other's substance use and health is critical because they are emerging and
effective targets of intervention and prevention.
PMID- 26414205
TI - Sexual revictimization, PTSD, and problem drinking in sexual assault survivors.
AB - Posttraumatic stress disorder (PTSD) and problem drinking are common and often co
occurring sequelae experienced by women survivors of adult sexual assault, yet
revictimization may mediate risk of symptoms over time. Structural equation
modeling was used to examine data from a 3-wave panel design with a large
(N=1012), ethnically diverse sample of women assault survivors to examine whether
repeated sexual victimization related to greater PTSD and problem drinking.
Structural equation modeling revealed that child sexual abuse was associated with
greater symptoms of PTSD and problem drinking and intervening sexual
victimization was associated with greater symptoms of PTSD and problem drinking
at both 1 and 2year follow-ups. We found no evidence, however, that PTSD directly
influenced problem drinking over the long term or vice versa, although they were
correlated at each timepoint. Revictimization during the study predicted
survivors' prospective PTSD and problem drinking symptoms inconsistently.
Implications and recommendations for future research are discussed.
PMID- 26414206
TI - Developmental trajectories of adolescent cannabis use and their relationship to
young adult social and behavioural adjustment: A longitudinal study of Australian
youth.
AB - This study aimed to identify distinct developmental trajectories (sub-groups of
individuals who showed similar longitudinal patterns) of cannabis use among
Australian adolescents, and to examine associations between trajectory group
membership and measures of social and behavioural adjustment in young adulthood.
Participants (n=852, 53% female) were part of the International Youth Development
Study. Latent class growth analysis was used to identify distinct trajectories of
cannabis use frequency from average ages 12 to 19, across 6 waves of data.
Logistic regression analyses and analyses of covariance were used to examine
relationships between trajectory group membership and young adult (average age:
21) adjustment, controlling for a range of covariates. Three trajectories were
identified: abstainers (62%), early onset users (11%), and late onset occasional
users (27%). The early onset users showed a higher frequency of antisocial
behaviour, violence, cannabis use, cannabis-related harms, cigarette use, and
alcohol harms, compared to the abstinent group in young adulthood. The late onset
occasional users reported a higher frequency of cannabis use, cannabis-related
harms, illicit drug use, and alcohol harms, compared to the abstinent group in
young adulthood. There were no differences between the trajectory groups on
measures of employment, school completion, post-secondary education, income,
depression/anxiety, or alcohol use problems. In conclusion, early onset of
cannabis use, even at relatively low frequency during adolescence, is associated
with poorer adjustment in young adulthood. Prevention and intervention efforts to
delay or prevent uptake of cannabis use should be particularly focussed on early
adolescence prior to age 12.
PMID- 26414207
TI - Pathogen Loading From Canada Geese Faeces in Freshwater: Potential Risks to Human
Health Through Recreational Water Exposure.
AB - Canada geese (Branta canadensis) faeces have been shown to contain pathogenic
protozoa and bacteria in numerous studies over the past 15 years. Further,
increases in both the Canada geese populations and their ideal habitat
requirements in the United States (US) translate to a greater presence of these
human pathogens in public areas, such as recreational freshwater beaches.
Combining these factors, the potential health risk posed by Canada geese faeces
at freshwater beaches presents an emerging public health issue that warrants
further study. Here, literature concerning human pathogens in Canada geese faeces
is reviewed and the potential impacts these pathogens may have on human health
are discussed. Pathogens of potential concern include Campylobacter jejuni,
Salmonella Typhimurium, Listeria monocytogenes, Helicobacter canadensis,
Arcobacter spp., Enterohemorragic Escherichia coli pathogenic strains, Chlamydia
psitacci, Cryptosporidium parvum and Giardia lamblia. Scenarios presenting
potential exposure to pathogens eluted from faeces include bathers swimming in
lakes, children playing with wet and dry sand impacted by geese droppings and
other common recreational activities associated with public beaches. Recent
recreational water-associated disease outbreaks in the US support the
plausibility for some of these pathogens, including Cryptosporidium spp. and C.
jejuni, to cause human illness in this setting. In view of these findings and the
uncertainties associated with the real health risk posed by Canada geese faecal
pathogens to users of freshwater lakes, it is recommended that beach managers use
microbial source tracking and conduct a quantitative microbial risk assessment to
analyse the local impact of Canada geese on microbial water quality during their
decision-making process in beach and watershed management.
PMID- 26414208
TI - The relationship between inflammation and neoangiogenesis of epicardial adipose
tissue and coronary atherosclerosis based on computed tomography analysis.
AB - OBJECTIVE: Previous studies indicate that epicardial adipose tissue (EAT)
biologically contributes to the progression of coronary atherosclerosis. We
evaluated the relationship between EAT pathology, represented by inflammation and
neoangiogenesis, and coronary atherosclerosis on computed tomography (CT) images.
METHODS: We performed CT examination in 45 patients scheduled for cardiac surgery
(coronary artery bypass graft [CABG], n = 21; non-CABG, n = 24) to assess
visceral adipose tissue (VAT) area, EAT volume, coronary calcium score (CCS), and
presence of non-calcified coronary plaque (NCP) on CT angiography. Each patient
was assessed with the numbers of CD68(+) individual macrophages and CD31(+)
neovessels in six random high-power fields (400*) of EAT samples subsequently
obtained during cardiac surgery. RESULTS: In three groups based on CCS (mild, 0
100; moderate, 101-400; severe, >400), the moderate group had the most extensive
macrophage infiltration (p = 0.0025) and neoangiogenesis (p = 0.0036) in EAT. The
patients with NCP had more extensive macrophage infiltration (p = 0.010) and
neoangiogenesis (p = 0.0043) in EAT than those without. On multivariate analysis
adjusted for age, sex, CABG versus. non-CABG, VAT area, and EAT volume, moderate
CCS and the presence of NCP showed significant correlations with increased
macrophage infiltration (beta = 0.65; p < 0.0001, and beta = 0.49; p = 0.0089,
respectively) and neoangiogenesis (beta = 0.55; p = 0.0011, and beta = 0.53; p =
0.012, respectively) in EAT. CONCLUSION: Inflammation and neoangiogenesis in EAT
independently correlate with moderate coronary calcification and presence of NCP,
suggesting that these two factors may have a role in promoting coronary
atherosclerosis.
PMID- 26414209
TI - Association between serum gamma-glutamyltransferase and the progression of
coronary artery calcification.
AB - BACKGROUND: Elevated serum gamma-glutamyltransferase (GGT) has been demonstrated
to be associated with coronary artery calcification (CAC). CAC progression is an
important marker of atherosclerosis and correlates with future cardiovascular
risk. However, there is a lack of research that directly examines the association
between serum GGT and CAC progression. The aim of this study was to elucidate the
association between serum GGT activity and CAC progression. METHODS: We enrolled
1246 asymptomatic participants who underwent repeated CAC score measurement
during routine health examinations. To eliminate the dependence of the inter scan
variability on the baseline CAC scores, square root-transformed CAC scores were
used to analyze CAC progression. In addition, the annualized rate of change in
CAC scores was computed. RESULTS: Serum GGT activities were significantly higher
in "progressors" than "nonprogressors". The prevalence of progression increased
with the GGT tertile (11.9%, 20.1% and 27.9% in the 1st, 2nd, and 3rd GGT
tertiles, respectively; p < 0.001). In the multivariate logistic regression
analysis, the odds ratio (95% confidence interval) for CAC score progression was
1.85 (1.14-3.00) in the highest GGT tertile group. By multivariate linear
regression analysis, baseline serum GGT activity demonstrated a positive
association with the annualized change in CAC score (beta = 0.002; p = 0.006)
after adjusting for cardiovascular risk factors. CONCLUSION: Elevated serum GGT
levels are independently associated with CAC progression. Serum GGT levels may be
a potential biomarker of future coronary atherosclerosis and prognosis.
PMID- 26414210
TI - A carotid extra-media thickness, PATIMA combined index and coronary artery
disease: Comparison with well-established indexes of carotid artery and fat
depots.
AB - BACKGROUND: The clinical utility of traditional cardiovascular (CV) risk factors
to predict coronary artery disease (CAD) is insufficient and limited. Our aim was
to evaluate the association between a novel ultrasound index of periarterial fat
and adventitia (carotid extra-media thickness; EMT) and the severity of CAD and
to compare this with well-known vascular indexes in patients with high and very
high CV risk. METHODS AND RESULTS: Four hundred twenty two patients scheduled for
elective coronary angiography were included in the study (age: 61.3 +/- 7.4
years; males 65%). Several clinical parameters of obesity were obtained as well
as the following ultrasound indexes: carotid EMT and intima-media thickness
(IMT), epicardial and pericardial fat thickness (EFT and PFT), and intra
abdominal fat thickness (IAT). These were then related to CAD severity in all
individuals. Our study patients had a very high estimated CV risk (82%), and most
(60%) fulfilled the MS criteria. Most individuals (71%) had CAD (>=50% stenosis)
with equal rates of one, two, or three-vessel disease, and critical (>=70%)
coronary stenosis was found in 40% of patients. Carotid EMT was significantly
increased in patients with CAD (812 +/- 116 vs 746 +/- 131 MUm) and patients with
critical coronary stenosis (829 +/- 119 vs 769 +/- 122 MUm) compared to the
appropriate control groups. Moreover, carotid EMT was significantly associated
with the severity of CAD. Carotid IMT and EFT (but not PFT and IAT) also revealed
significant relations to the number of diseased vessels. Carotid EMT and the new
proposed combined index (PATIMA = EMT/BMIx35 + IMT + EFTx60) were predictive for
CAD (AUC: 686 +/- 304 and 755 +/- 260, sensitivity: 60 and 62%, specificity: 76
and 81% for 772 MUm and 2015u). CONCLUSIONS: We present the first study showing
that the new vascular index (carotid EMT) and the proposed combined index PATIMA
are associated with the presence and the severity of CAD.
PMID- 26414211
TI - Mutations in CypA Binding Region of HIV-1 Capsid Affect Capsid Stability and
Viral Replication in Primary Macrophages.
AB - Mutations in the cyclophilin A (CypA) binding region in the HIV-1 capsid affect
their dependency on the known HIV-1 cofactor CypA and allow escape from the HIV-1
restriction factor Trim5alpha in human and simian cells. Here we study the effect
of these mutations in the CypA binding region of capsid on cofactor binding,
capsid destabilization, and viral replication in primary cells. We showed that
the viral capsid with mutations in the CypA binding region (CypA-BR) interacted
efficiently with CypA, but had an increased stability upon infection as compared
to the wild-type capsid. Interestingly, the wild-type virus was able to infect
monocyte-derived macrophages (MDM) more efficiently as compared to the CypA-BR
mutant variant. The lower infectivity of the CypA-BR mutant virus in MDM was
associated with lower levels of reverse transcription products. Similar to the
wild-type virus, the CypA-BR mutant variant was unable to induce a strong innate
response in primary macrophages. These data demonstrate that mutations in the
CypA binding site of the capsid resulted in higher capsid stability and hampered
infectivity in macrophages.
PMID- 26414213
TI - Stereotactic body radiotherapy for head and neck cancer: an addition to the
armamentarium against head and neck cancer.
AB - In the recent years, stereotactic body radiation therapy (SBRT) has emerged as a
potential therapy for head and neck malignancies. Although early results appear
to be promising, serious acute and late effects have been observed, mainly in
patients who have had prior external beam radiotherapy. This review will discuss
the radiobiology of SBRT, clinical rationale and outcomes for SBRT in head and
neck cancers and focus on the benefits and potential limitations in both de novo
and re-irradiation settings.
PMID- 26414214
TI - Erratum: Big Data Bioinformatics by C. S. Greene, J. Tan, M. Ung, J. H. Moore,
and C. Cheng.
PMID- 26414212
TI - Time Course and Size of Blood-Brain Barrier Opening in a Mouse Model of Blast
Induced Traumatic Brain Injury.
AB - An increasing number of studies have reported blood-brain barrier (BBB)
dysfunction after blast-induced traumatic brain injury (bTBI). Despite this
evidence, there is limited quantitative understanding of the extent of BBB
opening and the time course of damage after blast injury. In addition, many
studies do not report kinematic parameters of head motion, making it difficult to
separate contributions of primary and tertiary blast-loading. Detailed
characterization of blast-induced BBB damage may hold important implications for
serum constituents that may potentially cross the compromised barrier and
contribute to neurotoxicity, neuroinflammation, and persistent neurologic
deficits. Using an in vivo bTBI model, systemic administration of sodium
fluorescein (NaFl; 376 Da), Evans blue (EB; 69 kDa when bound to serum albumin),
and dextrans (3-500 kDa) was used to estimate the pore size of BBB opening and
the time required for recovery. Exposure to blast with 272 +/- 6 kPa peak
overpressure, 0.69 +/- 0.01 ms duration, and 65 +/- 1 kPa*ms impulse resulted in
significant acute extravasation of NaFl, 3 kDa dextran, and EB. However, there
was no significant acute extravasation of 70 kDa or 500 kDa dextrans, and minimal
to no extravasation of NaFl, dextrans, or EB 1 day after exposure. This study
presents a detailed analysis of the time course and pore size of BBB opening
after bTBI, supported by a characterization of kinematic parameters associated
with blast-induced head motion.
PMID- 26414218
TI - 2-Arachidonylglycerol Protects Primary Astrocytes Exposed to Oxygen-Glucose
Deprivation Through a Blockade of NDRG2 Signaling and STAT3 Phosphorylation.
AB - The human N-Myc downstream-regulated gene 2 (NDRG2) is expressed in astrocytes,
and may be involved in the modulation of gliacyte function in the central nervous
system. Our previous study found suppression of NDRG2 up-regulation in reactive
astrocytes in cerebral ischemic tolerance. 2-Arachidonylglycerol (2-AG) can
induce cerebral ischemic tolerance. However, the underlying mechanism of NDRG2 in
cytoprotection induced by 2-AG in primary astrocytesis still unknown. In this
study, we investigated the role of NDRG2 in cerebral ischemic tolerance induced
by 2-AG after oxygen-glucose deprivation (OGD) in primary astrocytes. The results
showed that primary astrocytes exposed to OGD resulted in marked increase of
lactate dehydrogenase (LDH) release and decrease of methyl thiazolyl tetrazolium
(MTT) reduction activity in comparison to control cultures. The levels of NDRG2
and phospho-signal transducer and activator of transcription 3 (pSTAT3) in the
OGD group were comparably higher than those in the control group, and the up
regulation of NDRG2 and pSTAT3 was suppressed in NDRG2 siRNA group. The cell
viability in the 2-AG group was higher than that in the OGD group, and
transfecting the NDRG2 pSRL-CDH1-GFP vector reversed the protective effects of 2
AG. The levels of NDRG2 and pSTAT3 in the 2-AG group were lower than those in the
OGD group. 2-AG suppressed STAT3 phosphorylation by decreased expression of
NDRG2. In conclusion, 2-AG protects primary astrocytes exposed to oxygen-glucose
deprivation through a blockade of NDRG2 signaling and STAT3 phosphorylation.
These findings bring insight to the roles of NDRG2 in ischemic-hypoxic injury and
provide novel potential targets for future potent clinical therapies on cerebral
ischemia injury.
PMID- 26414219
TI - Estimation of residue depletion of cyadox and its marker residue in edible
tissues of pigs using physiologically based pharmacokinetic modelling.
AB - Physiologically based pharmacokinetic (PBPK) models are powerful tools to predict
tissue distribution and depletion of veterinary drugs in food animals. However,
most models only simulate the pharmacokinetics of the parent drug without
considering their metabolites. In this study, a PBPK model was developed to
simultaneously describe the depletion in pigs of the food animal antimicrobial
agent cyadox (CYA), and its marker residue 1,4-bisdesoxycyadox (BDCYA). The CYA
and BDCYA sub-models included blood, liver, kidney, gastrointestinal tract,
muscle, fat and other organ compartments. Extent of plasma-protein binding, renal
clearance and tissue-plasma partition coefficients of BDCYA were measured
experimentally. The model was calibrated with the reported pharmacokinetic and
residue depletion data from pigs dosed by oral gavage with CYA for five
consecutive days, and then extrapolated to exposure in feed for two months. The
model was validated with 14 consecutive day feed administration data. This PBPK
model accurately simulated CYA and BDCYA in four edible tissues at 24-120 h after
both oral exposure and 2-month feed administration. There was only slight
overestimation of CYA in muscle and BDCYA in kidney at earlier time points (6-12
h) when dosed in feed. Monte Carlo analysis revealed excellent agreement between
the estimated concentration distributions and observed data. The present model
could be used for tissue residue monitoring of CYA and BDCYA in food animals, and
provides a foundation for developing PBPK models to predict residue depletion of
both parent drugs and their metabolites in food animals.
PMID- 26414220
TI - Denosumab-treated Giant Cell Tumor of Bone Exhibits Morphologic Overlap With
Malignant Giant Cell Tumor of Bone.
AB - Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm
characterized by an abundance of osteoclastic giant cells that are induced by the
neoplastic mononuclear cells; the latter express high levels of receptor
activator of nuclear factor kappa-B ligand (RANKL). Denosumab, a RANKL inhibitor,
which is clinically used to treat GCT, leads to a marked alteration in the
histologic appearance of the tumor with giant cell depletion and new bone
deposition, leading to substantial histologic overlap with other primary tumors
of bone. Most significantly, denosumab-treated GCT (tGCT) with abundant bone
deposition may mimic de novo osteosarcoma, or GCT that has undergone malignant
transformation. To histologically characterize tGCT, we identified 9 cases of GCT
biopsied or resected after denosumab treatment. tGCT cases included 16 specimens
from 9 patients including 6 female and 3 male individuals aged 16 to 47 (median
32) years. Duration of treatment varied from 2 to 55 months. We compared these
tumors with malignant neoplasms arising in GCTs (n=9). The histology of tGCT was
variable but appeared to relate to the length of therapy. All tGCTs showed marked
giant cell depletion. Early lesions were highly cellular, and the combination of
cellularity, atypia, and haphazard bone deposition caused the lesion to resemble
high-grade osteosarcoma. Unlike de novo high-grade osteosarcoma or malignancies
arising in GCT, however, tGCT showed less severe atypia, reduced mitotic
activity, and lack of infiltrative growth pattern. Tumor in patients on prolonged
therapy showed decreased cellularity and abundant new bone, deposited as broad,
rounded cords or long, curvilinear arrays. The latter morphology was reminiscent
of low-grade central osteosarcoma, but, unlike low-grade central osteosarcoma,
tGCT was negative for MDM2 and again lacked an infiltrative growth pattern.
Overall, tGCT may have a wide range of morphologic appearances. Because the
treated tumors bear little resemblance to their pretreatment counterparts,
careful attention to the history of denosumab administration is crucial to avoid
a misdiagnosis with an important impact on therapy. Unlike malignant GCTs, tGCTs
lack significant nuclear atypia, mitotic activity, and infiltration of
preexisting bone, but instead show a unique pattern of intralesional bone
deposition.
PMID- 26414221
TI - Eosinophilic, Solid, and Cystic Renal Cell Carcinoma: Clinicopathologic Study of
16 Unique, Sporadic Neoplasms Occurring in Women.
AB - A unique renal neoplasm characterized by eosinophilic cytoplasm and solid and
cystic growth was recently reported in patients with tuberous sclerosis complex
(TSC). We searched multiple institutional archives and consult files in an
attempt to identify a sporadic counterpart. We identified 16 morphologically
identical cases, all in women, without clinical features of TSC. The median age
was 57 years (range, 31 to 75 y). Macroscopically, tumors were tan and had a
solid and macrocystic (12) or only solid appearance (4). Average tumor size was
50 mm (median, 38.5 mm; range, 15 to 135 mm). Microscopically, the tumors showed
solid areas admixed with variably sized macrocysts and microcysts that were lined
by cells with a pronounced hobnail arrangement. The cells had voluminous
eosinophilic cytoplasm with prominent granular cytoplasmic stippling and round to
oval nuclei with prominent nucleoli. Scattered histiocytes and lymphocytes were
invariably present. Thirteen of 16 patients were stage pT1; 2 were pT2, and 1 was
pT3a. The cells demonstrated a distinct immunoprofile: nuclear PAX8 expression,
predominant CK20-positive/CK7-negative phenotype, patchy AMACR staining, but no
CD117 reactivity. Thirteen of 14 patients with follow-up were alive and without
disease progression after 2 to 138 months (mean: 53 mo; median: 37.5 mo); 1
patient died of other causes. Although similar to a subset of renal cell
carcinomas (RCCs) seen in TSC, we propose that sporadic "eosinophilic, solid, and
cystic RCC," which occurs predominantly in female individuals and is
characterized by distinct morphologic features, predominant CK20-positive/CK7
negative immunophenotype, and indolent behavior, represents a novel subtype of
RCC.
PMID- 26414222
TI - Radiation-induced Sarcomas Occurring in Desmoid-type Fibromatosis Are Not Always
Derived From the Primary Tumor.
AB - Desmoid-type fibromatosis is a rare, highly infiltrative, locally destructive
neoplasm that does not metastasize, but recurs often after primary surgery.
Activation of the Wnt/beta-catenin pathway is the pathogenic mechanism, caused by
an activating mutation in exon 3 of CTNNB1 (85% of the sporadic patients).
Radiotherapy is a frequent treatment modality with a local control rate of
approximately 80%. In very rare cases, this may result in the development of
radiation-induced sarcoma. It is unclear whether these sarcomas develop from the
primary tumor or arise de novo in normal tissue. In 4 tertiary referral centers
for sarcoma, 6 cases of desmoid-type fibromatosis that subsequently developed
sarcoma after radiotherapy were collected. The DNA sequence of CTNNB1 exon 3 in
the desmoid-type fibromatosis and the subsequent postradiation sarcoma was
determined. Sarcomas developed 5 to 21 years after the diagnosis of desmoid-type
fibromatosis and included 2 osteosarcomas, 2 high-grade undifferentiated
pleomorphic sarcomas, 1 fibrosarcoma, and 1 undifferentiated spindle cell
sarcoma. Three patients showed a CTNNB1 hotspot mutation (T41A, S45F, or S45N) in
both the desmoid-type fibromatosis and the radiation-induced sarcoma. The other 3
patients showed a CTNNB1 mutation in the original desmoid-type fibromatosis (2
with a T41A and 1 with an S45F mutation), which was absent in the sarcoma. In
conclusion, postradiation sarcomas that occur in the treatment area of desmoid
type fibromatosis are extremely rare and can arise through malignant
transformation of CTNNB1-mutated desmoid fibromatosis cells, but may also
originate from CTNNB1 wild-type normal cells lying in the radiation field.
PMID- 26414223
TI - Nuclear Expression of CAMTA1 Distinguishes Epithelioid Hemangioendothelioma From
Histologic Mimics.
AB - Epithelioid hemangioendothelioma (EHE) is a malignant endothelial neoplasm
characterized by recurrent translocations involving chromosomal regions 1p36.3
and 3q25, resulting in the formation of a WWTR1-CAMTA1 fusion gene in
approximately 90% of cases; a small subset (<5%) have a YAP1-TFE3 fusion gene.
The WWTR1-CAMTA1 fusion gene leads to overexpression of both genes. WWTR1 protein
is expressed in many different cell types, whereas CAMTA1 expression is normally
limited to the brain. A prior study using a polyclonal antibody directed against
regions within the C-terminus of CAMTA1 reported widespread expression in both
normal tissues and diverse tumor types. In contrast, a recent study using a
different polyclonal antibody directed against the C-terminus of CAMTA1 suggested
that this other antibody is a potentially useful diagnostic marker for EHE. Our
study aimed to validate this finding in a large series of EHE cases and to
determine whether CAMTA1 is expressed in other epithelioid mesenchymal tumors
that may mimic EHE. Protein expression of CAMTA1 was evaluated in whole-tissue
sections of 204 tumors using a polyclonal anti-CAMTA1 antibody: 59 EHE (48
conventional, 11 "malignant"; 4 with known TFE3 gene rearrangement); 70 other
epithelioid vascular tumors; and 75 nonendothelial epithelioid mesenchymal
neoplasms. In total, 51/59 cases (86%) of EHE showed diffuse nuclear staining for
CAMTA1, including 44/48 cases (92%) with conventional histology and 7/11 cases
(64%) with "malignant" histology. Of the 8 CAMTA1-negative tumors, 6 were
positive for TFE3. With the exception of 1 case previously diagnosed as
epithelioid angiosarcoma on core biopsy, all other tumor types examined were
negative for CAMTA1. In conclusion, in keeping with the reported frequency of
WWTR1-CAMTA1 in EHE, nuclear CAMTA1 expression is identified in the majority of
EHE cases, whereas other epithelioid mesenchymal neoplasms are negative for
CAMTA1. These findings support the diagnostic utility of immunohistochemistry for
CAMTA1 in distinguishing EHE from histologic mimics, in particular benign
epithelioid vascular tumors, epithelioid angiosarcoma, and epithelioid sarcoma,
an important distinction given the differences in biological potential and
clinical course.
PMID- 26414224
TI - Combined "Infiltrating Astrocytoma/Pleomorphic Xanthoastrocytoma" Harboring IDH1
R132H and BRAF V600E Mutations.
AB - Pleomorphic xanthoastrocytoma (PXA) has rarely been reported in combination with
infiltrating glioma, historically interpreted as a "collision tumor." Isocitrate
dehydrogenase 1 (IDH1) and BRAF V600E mutations are usually not concurrent. The
former is typical of adult infiltrating gliomas, and the latter is identified in
a variety of primary central nervous system neoplasms, including PXA,
ganglioglioma, pilocytic astrocytoma, and rarely infiltrating gliomas. We report
the case of a 56-year-old man presenting with seizures and headaches. Magnetic
resonance imaging revealed a large right temporal lobe mass with low T1 and high
T2/FLAIR signal and a discrete contrast-enhancing focus. Histologically, the
tumor showed 2 distinct components: an infiltrating astrocytoma harboring 5
mitoses/10 high-power fields and a relatively circumscribed focus, resembling PXA
with, at most, 2 mitoses/10 high-power fields. No microvascular proliferation or
necrosis was present in either component. The infiltrating astrocytoma component
contained numerous axons, whereas the PXA-like component had sparse axons, as
demonstrated by the neurofilament immunostain. Both components were positive for
the mutant IDH1 R132H and showed loss of ATRX expression, whereas BRAF V600E was
restricted to the PXA-like component. On sequencing of the 2 components
separately after microdissection, both showed identical IDH1 R132H and TP53 R273C
point mutations, whereas the BRAF V600E mutation was limited to the PXA-like
component. These findings are consistent with clonal expansion of a
morphologically distinct focus, harboring a private BRAF V600E mutation within an
IDH1-mutant glioma. Intratumoral heterogeneity and clonal evolution, as seems to
have occurred here, suggest reevaluation of "collision tumors" as a concept.
PMID- 26414225
TI - Neutropenic Enterocolitis: New Insights Into a Deadly Entity.
AB - Neutropenic enterocolitis (NE) is a deadly ileocecal-based disease seen in
patients with a recent history of chemotherapy. As histology is not included in
the current diagnostic criteria, the pathologic features of NE are poorly
understood. We undertook a multi-institutional study of NE, and report helpful
clinical clues, such as immunosuppression (n=20/20), recent chemotherapy
(n=17/18), neutropenia (n=16/18) gastrointestinal symptoms (n=19/19), abnormal
imaging studies of the cecum/right colon (n=11/14), and positive microbiological
studies (n=13/15). Fever (n=9/15) and sepsis (n=8/16) were also common.
Pathologically, the cecum/right colon was always involved (n=17/17), but findings
were identified in other bowel segments as well. NE lesions consisted of patchy
necrosis (n=18/20), infiltrating organisms (n=17/20), hemorrhage (n=15/20), ulcer
(n=15/19), edema (n=15/20), and depletion of inflammatory cells (n=15/20).
Seventy-nine percent (n=15/19) of patients with histologically confirmed NE died:
47% (n=7/15) of these deaths were attributed to NE and the remainder to the
patients' underlying conditions. Importantly, we observed a clinical diagnostic
discordancy rate of 35% (n=9/26): 15% (n=3/20) of histologically confirmed NE
were clinically unsuspected, and 26% (n=6/23) of clinically suspected NE
represented a different disease process. Alternative diagnoses included
unspecified colitis, infection, graft-versus-host disease, relapsed malignancy,
mycophenolate injury, appendicitis, and ischemia. The causes of death in patients
with NE mimics included unrecognized appendicitis and unrecognized graft-versus
host disease. To improve diagnostic accuracy, we propose that histology be
required for a diagnosis of "definitive NE," with other clinically suspicious
cases reported as "suspicious for NE" until all other possible diagnoses have
been reasonably excluded.
PMID- 26414226
TI - Assessment of Stone Complexity for PCNL: A Systematic Review of the Literature,
How Best Can We Record Stone Complexity in PCNL?
AB - INTRODUCTION: This study aims to systematically review the literature reporting
tools for scoring stone complexity and the stratification of outcomes by stone
complexity. In doing so, we aim to determine whether the evidence favors uniform
adoption of any one scoring system. METHODS: PubMed and Embase databases were
systematically searched for relevant studies from 2004 to 2014. Reports selected
according to predetermined inclusion and exclusion criteria were appraised in
terms of methodologic quality and their findings summarized in structured tables.
RESULTS: After review, 15 studies were considered suitable for inclusion. Four
distinct scoring systems were identified and a further five studies that aimed to
validate aspects of those scoring systems. Six studies reported the
stratification of outcomes by stone complexity, without specifically defining a
scoring system. All studies reported some correlation between stone complexity
and stone clearance. Correlation with complications was less clearly established,
where investigated. CONCLUSIONS: This review does not allow us to firmly
recommend one scoring system over the other. However, the quality of evidence
supporting validation of the Guy's Stone Score is marginally superior, according
to the criteria applied in this study. Further evaluation of the interobserver
reliability of this scoring system is required.
PMID- 26414227
TI - Behavioral Programs for Type 2 Diabetes Mellitus: A Systematic Review and Network
Meta-analysis.
AB - BACKGROUND: Behavioral programs may improve outcomes for individuals with type 2
diabetes mellitus, but there is a large diversity of behavioral interventions and
uncertainty about how to optimize the effectiveness of these programs. PURPOSE:
To identify factors moderating the effectiveness of behavioral programs for
adults with type 2 diabetes. DATA SOURCES: 6 databases (1993 to January 2015),
conference proceedings (2011 to 2014), and reference lists. STUDY SELECTION:
Duplicate screening and selection of 132 randomized, controlled trials evaluating
behavioral programs compared with usual care, active controls, or other
behavioral programs. DATA EXTRACTION: One reviewer extracted and another verified
data. Two reviewers independently assessed risk of bias. DATA SYNTHESIS:
Behavioral programs were grouped on the basis of program content and delivery
methods. A Bayesian network meta-analysis showed that most lifestyle and diabetes
self-management education and support programs (usually offering >= 11 contact
hours) led to clinically important improvements in glycemic control (>= 0.4%
reduction in hemoglobin A1c [HbA1c]), whereas most diabetes self-management
education programs without added support-especially those offering 10 or fewer
contact hours-provided little benefit. Programs with higher effect sizes were
more often delivered in person than via technology. Lifestyle programs led to the
greatest reductions in body mass index. Reductions in HbA1c seemed to be greater
for participants with a baseline HbA1c level of 7.0% or greater, adults younger
than 65 years, and minority persons (subgroups with >= 75% nonwhite
participants). LIMITATIONS: All trials had medium or high risk of bias. Subgroup
analyses were indirect, and therefore exploratory. Most outcomes were reported
immediately after the interventions. CONCLUSION: Diabetes self-management
education offering 10 or fewer hours of contact with delivery personnel provided
little benefit. Behavioral programs seem to benefit persons with suboptimal or
poor glycemic control more than those with good control. PRIMARY FUNDING SOURCE:
Agency for Healthcare Research and Quality. (PROSPERO registration number:
CRD42014010515).
PMID- 26414228
TI - A biomimetic underwater vehicle actuated by waves with ionic polymer-metal
composite soft sensors.
AB - The ionic polymer-metal composite (IPMC) is a soft material based actuator and
sensor and has a promising potential in underwater application. This paper
describes a hybrid biomimetic underwater vehicle that uses IPMCs as sensors.
Propelled by the energy of waves, this underwater vehicle does not need an
additional energy source. A physical model based on the hydrodynamics of the
vehicle was developed, and simulations were conducted. Using the Poisson-Nernst
Planck system of equations, a physics model for the IPMC sensor was proposed. For
this study, experimental apparatus was developed to conduct hydrodynamic
experiments for both the underwater vehicle and the IPMC sensors. By comparing
the experimental and theoretical results, the speed of the underwater vehicle and
the output of the IPMC sensors were well predicted by the theoretical models. A
maximum speed of 1.08 * 10(-1) m s(-1) was recorded experimentally at a wave
frequency of 1.6 Hz. The peak output voltage of the IPMC sensor was 2.27 * 10(-4)
V, recorded at 0.8 Hz. It was found that the speed of the underwater vehicle
increased as the wave frequency increased and the IPMC output decreased as the
wave frequency increased. Further, the energy harvesting capabilities of the
underwater vehicle hosting the IPMCs were tested. A maximum power of 9.50 * 10(
10) W was recorded at 1.6 Hz.
PMID- 26414229
TI - Responses to and Outcomes of Treatment of Autoimmune Cerebellar Ataxia in Adults.
AB - IMPORTANCE: Classic Purkinje cell cytoplasmic antibody type 1 (PCA-1, or anti-Yo)
paraneoplastic cerebellar ataxia has a poor prognosis, yet little has been
published otherwise regarding treatment responses and outcomes among patients
with autoimmune cerebellar ataxia. OBJECTIVES: To investigate treatment responses
and outcomes in adults with autoimmune cerebellar ataxia. DESIGN, SETTING, AND
PARTICIPANTS: A cohort study conducted at Mayo Clinic, Rochester, Minnesota,
included 118 patients who had ataxia, were 18 years or older, were seropositive
for at least 1 neural autoantibody, had received at least 1 immunotherapy or
cancer therapy, and had neurologist-reported outcomes documented from January 1,
1989, through December 31, 2013. Data were collected from May 14, 2013, through
August 9, 2014, and analyzed from August 9, 2014, through April 27, 2015.
Responses to immunotherapy (corticosteroids, intravenous immunoglobulin, plasma
exchange, and immunosuppressants) and ambulatory outcomes were compared between
different subgroups. Subgroups were classified as paraneoplastic vs
nonparaneoplastic disorders; neuronal nuclear and/or cytoplasmic (NNC) antibody
positivity vs plasma membrane protein (PMP) antibody positivity; and glutamic
acid decarboxylase 65-kDa isoform (GAD65) antibody positivity vs PMP antibody
positivity. MAIN OUTCOMES AND MEASURES: Response to therapy and ambulatory
ability, with univariate logistic regression and Kaplan-Meier analyses. RESULTS:
Inclusion criteria were met by 118 patients. Median age at onset of neurologic
symptoms was 58 (range, 27-83) years, and 87 patients (73.7%) were women. Median
duration from symptom onset to last follow-up was 25 (range, 2-223) months. Sixty
three patients had paraneoplastic and 55 patients had nonparaneoplastic ataxic
disorders. Eighty-one patients were seropositive for NNC antibodies (most
commonly PCA-1 [anti-Yo], antineuronal nuclear antibody type 1 [anti-Hu], and
GAD65 antibody); 22 patients, for neural PMP receptor or ion channel antibodies
(most commonly targeting P/Q- or N-type voltage-gated calcium channels); and 15
patients, for antibodies from both categories. Neurologic improvements occurred
in 54 patients (with a robust change in ambulatory ability in 22) attributable to
immunotherapy; univariate regression analysis revealed that improvements were
significantly more common among patients with nonparaneoplastic disorders (P =
.03) and those with exclusively PMP antibodies (P = .02). Kaplan-Meier analyses
revealed that progression to wheelchair dependence occurred significantly faster
among patients with NNC antibody positivity only (P = .02), although those with
GAD65 autoimmunity progressed to wheelchair dependence at a rate similar to those
with PMP autoimmunity (P = .92). CONCLUSIONS AND RELEVANCE: Although autoimmune
ataxia is usually severe, treatment responses can be gratifying, particularly in
patients with nonparaneoplastic disorders and in those harboring autoantibodies
directed against GAD65 or neural PMPs.
PMID- 26414231
TI - Comment on Accurate Data Process for Nanopore Analysis.
PMID- 26414230
TI - Abnormal Expression of Urea Transporter Protein in a Rat Model of Hepatorenal
Syndrome Induced by Succinylated Gelatin.
AB - BACKGROUND: Hepatorenal syndrome (HRS) is a serious complication of advanced
chronic liver disease. Abdominal compartment syndrome (ACS) occurs with
dysfunction of multiple organs when abdominal pressure increases. Here, we report
on a novel model of ACS with ascites and a model of HRS in rats to observe the
urea transporter protein (UT) expression in the 2 models. MATERIAL AND METHODS: A
liver cirrhosis model was induced by CCl4. After changes of liver histopathology
were observed, rats were injected intraperitoneally with succinylated gelatin to
establish a model of ACS and HRS. Then, changes in BUN, Cr, and renal
histopathology were detected. Moreover, the UT in ACS and HRS were also
quantified. RESULTS: The surfaces of liver in the cirrhotic group became coarse,
with visible small nodules and became yellow and greasy. The normal structure of
the hepatic lobules were destroyed, and hyperplasia of fibrotic tissue and pseudo
lobe was observed. The levels of BUN and Cr were significantly increased in rats
suffering from ACS and HRS, respectively, compared to their control groups. In
addition, the mRNA levels of UT-A2 and UT-A3 decreased in rats with HRS compared
to cirrhotic rats. However, there was no significant difference between the mRNA
levels of UT-A2, UT-A3, and UT-B in rats with ACS vs. normal rats. CONCLUSIONS:
It is feasible to model ACS in rats by injecting succinylated gelatin into the
abdominal cavity. Increasing the intra-abdominal pressure by succinylated gelatin
is also a novel approach for modeling HRS in cirrhotic rats. Compared with
control rats, there is an abnormal mRNA expression of UT in ACS rats and HRS
rats.
PMID- 26414232
TI - Pituitary Apoplexy.
AB - Pituitary apoplexy, a rare clinical syndrome secondary to abrupt hemorrhage or
infarction, complicates 2%-12% of pituitary adenomas, especially nonfunctioning
tumors. Headache of sudden and severe onset is the main symptom, sometimes
associated with visual disturbances or ocular palsy. Signs of meningeal
irritation or altered consciousness may complicate the diagnosis. Precipitating
factors (increase in intracranial pressure, arterial hypertension, major surgery,
anticoagulant therapy or dynamic testing, etc) may be identified. Corticotropic
deficiency with adrenal insufficiency may be life threatening if left untreated.
Computed tomography or magnetic resonance imaging confirms the diagnosis by
revealing a pituitary tumor with hemorrhagic and/or necrotic components. Formerly
considered a neurosurgical emergency, pituitary apoplexy always used to be
treated surgically. Nowadays, conservative management is increasingly used in
selected patients (those without important visual acuity or field defects and
with normal consciousness), because successive publications give converging
evidence that a wait-and-see approach may also provide excellent outcomes in
terms of oculomotor palsy, pituitary function and subsequent tumor growth.
However, it must be kept in mind that studies comparing surgical approach and
conservative management were retrospective and not controlled.
PMID- 26414234
TI - A Pilot Study of Safety and Efficacy of Cranial Electrotherapy Stimulation in
Treatment of Bipolar II Depression.
AB - This double-blind, sham-controlled study sought to investigate the effectiveness
of cranial electrotherapy stimulation (CES) for the treatment of bipolar II
depression (BD II). After randomization, the active group participants (n = 7)
received 2 mA CES treatment for 20 minutes five days a week for 2 weeks, whereas
the sham group (n = 9) had the CES device turned on and off. Symptom non
remitters from both groups received an additional 2 weeks of open-label active
treatment. Active CES treatment but not sham treatment was associated with a
significant decrease in the Beck Depression Inventory (BDI) scores from baseline
to the second week (p = 0.003) maintaining significance until week 4 (p = 0.002).
There was no difference between the groups in side effects frequency. The results
of this small study indicate that CES may be a safe and effective treatment for
BD II suggesting that further studies on safety and efficacy of CES may be
warranted.
PMID- 26414235
TI - Protection afforded by quercetin against H2O2-induced apoptosis on PC12 cells via
activating PI3K/Akt signal pathway.
AB - Cell damage and apoptosis induced by oxidative stress have been involved in
various neurodegenerative diseases. This study aims to explore the neuro
protective effects of quercetin on PC12 cells apoptosis induced by hydrogen
peroxide (H(2)O(2)) and the underlying mechanisms. The cell viability was
detected, as well as the production of reactive oxygen species (ROS), lactate
dehydrogenase (LDH) leakage, and the activities of glutathione peroxidase (GSH
Px), superoxide dismutase (SOD) and malondialdehyde (MDA) of the cells in
control, H(2)O(2) and quercetin groups. It finally turned out that quercetin
might protect PC12 cells against the negative effect of H(2)O(2) by decreasing of
LDH release, ROS concentration and MDA level and regaining the GSH-Px and SOD
activities. To investigate the mechanism, LY294002 was introduced, the
phosphatidylinositol-3-kinase (PI3K) inhibitor. Bax/Bcl-2 ratio and Akt
phosphorylation (p-Akt) were examined by Western blot analysis. The data showed
that LY294002 almost had the same effects with H(2)O(2), which was also
significantly reversed by quercetin could enhance Bax/Bcl-2 ratio and adjust the
p-Akt expression, which indicated quercetin might protect PC12 cells against the
negative effect of H(2)O(2) via activating the PI3K/Akt signal pathway.
PMID- 26414233
TI - Executive Summary to EDC-2: The Endocrine Society's Second Scientific Statement
on Endocrine-Disrupting Chemicals.
AB - This Executive Summary to the Endocrine Society's second Scientific Statement on
environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the
key points of the complete statement. The full Scientific Statement represents a
comprehensive review of the literature on seven topics for which there is strong
mechanistic, experimental, animal, and epidemiological evidence for endocrine
disruption, namely: obesity and diabetes, female reproduction, male reproduction,
hormone-sensitive cancers in females, prostate cancer, thyroid, and
neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A,
phthalates, pesticides, persistent organic pollutants such as polychlorinated
biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because
these chemicals had the greatest depth and breadth of available information. The
Statement also included thorough coverage of studies of developmental exposures
to EDCs, especially in the fetus and infant, because these are critical life
stages during which perturbations of hormones can increase the probability of a
disease or dysfunction later in life. A conclusion of the Statement is that
publications over the past 5 years have led to a much fuller understanding of the
endocrine principles by which EDCs act, including nonmonotonic dose-responses,
low-dose effects, and developmental vulnerability. These findings will prove
useful to researchers, physicians, and other healthcare providers in translating
the science of endocrine disruption to improved public health.
PMID- 26414236
TI - A randomized multicenter study of minilaparotomy cholecystectomy versus
laparoscopic cholecystectomy with ultrasonic dissection in both groups.
AB - OBJECTIVE: Ultrasonic dissection (UsD) has been used in laparoscopic
cholecystectomy (LC), though it is not the golden standard technique. Applying
UsD to cholecystectomy by minilaparotomy (MC) is less common and there are no
prospective randomized trials comparing these two techniques. Therefore, we
conducted the present study to investigate the use of the UsD in the MC versus
the LC procedure. MATERIAL AND METHODS: Initially 104 patients with non
complicated symptomatic gallstone disease were randomized into MC (n = 53) or LC
(n = 51) groups, both groups using UsD, over a period of 2 years (2013-2015). The
study groups were similar in terms of age and American Society of
Anesthesiologists (ASA) physical status score. RESULTS: The demographic variables
and the surgical data were similar in the study groups. Similar low postoperative
pain scores were reported in the two study groups during the first four hours
after surgery. The incidence of nausea/vomiting was similar between the two study
groups, 47% in the MC group versus 42% in the LC group. However, the patients in
the MC group were treated more frequently with antiemetics, the incidence being
39% in the MC group versus 21% in the LC group (p = 0.02). The pain at rest at
24h after the surgery was similar in the two study groups, but the LC patients
reported less pain at the normal activity, the mean of numerical rating scale
(NRS) of 0-10 score being 3.9 in the MC group versus 2.9 in the LC group (p =
0.05), and the pain at the quick movement/coughing, the mean NRS being 4.9 in the
MC group versus 3.2 in the LC group (p = 0.005). The length of sick leave was
17.4 days in the MC group and 14.4 days in the LC group (p = 0.05). CONCLUSION:
Our results suggest that both MC and LC are feasible and safe options for mini
invasive cholecystectomy. A new finding with clinical relevance in the present
work is a relatively similar short-term outcome in the MC and LC although the LC
patients reported significantly lower pain score 24 hours postoperatively and a
shorter convalescence.
PMID- 26414237
TI - Application and Utility of iPads in Pediatric Tele-echocardiography.
AB - BACKGROUND: Telemedicine is used with increasing frequency to improve patient
care in remote areas. The interpretation of medical imaging on iPad((r)) (Apple,
Cupertino, CA) tablets has been reported to be accurate. There are no studies on
the use of iPads for interpretation of pediatric echocardiograms. We compared the
quality of echo images, diagnostic accuracy, and review time using three
different modalities: remote access on an iPad Air (iPad), remote access via a
computer (Remote), and direct access on a computer linked through Ethernet to the
server, the "gold standard" (Direct). MATERIALS AND METHODS: Fifty consecutive
archived pediatric echocardiograms were interpreted using the three modalities.
Studies were analyzed blindly by three pediatric cardiologists; review time,
diagnostic accuracy, and image quality were documented. Diagnostic accuracy was
assessed by comparing the study diagnoses with the official diagnosis in the
patient's chart. Discrepancies between diagnoses were graded as major (more than
one grade difference) or minor (one grade difference in severity of lesion).
RESULTS: There were no significant differences in accuracy among the three
modalities. There was one major discrepancy (size of patent ductus arteriosus);
all others were minor, hemodynamically insignificant. Image quality ratings were
better for iPad than Remote; Direct had the highest ratings. Review times (mean
[standard deviation] minutes) were longest for iPad (5.89 [3.87]) and then Remote
(4.72 [2.69]), with Direct having the shortest times (3.52 [1.42]) (p < 0.0001).
CONCLUSIONS: Pediatric echocardiograms can be interpreted using convenient,
portable devices while preserving accuracy and quality with slightly longer
review times (1-2 min). These findings are important in the current era of
increasing need for mobile health.
PMID- 26414238
TI - Intra-Articular Transplantation of Allogeneic BMMSCs Rehabilitates Cartilage
Injury of Antigen-Induced Arthritis.
AB - Apart from the immunosuppressive property, which has been widely investigated in
the treatment of various autoimmune diseases, bone marrow mesenchymal stem cells
(BMMSCs) also exhibit the chondrogenic capacity. Recently, BMMSCs have attracted
more and more attention in the remission of rheumatoid arthritis (RA) and the
reconstruction of cartilage injury. In addition to the significant regulatory
hurdles of systemic treatment by BMMSCs, the poor inhibitory efficiency on
articular inflammatory reaction and the inferior result of preventing the
persistent destruction of cartilage were observed. Herein, toward the ovalbumin
(OVA)-induced arthritis in rabbits, the in situ transplantation of fibrin gel
encapsulated BMMSCs to osteochondral defect was confirmed to result in the
decreased levels of cytokines, such as interleukin-1beta, interleukin-6, tumor
necrosis factor-alpha, and anti-OVA antibody, in the serum. What is more, the
implantation of BMMSCs also inhibited the proliferation of antigen-specific
lymphocytes. Meanwhile, the fibrin gel-encapsulated BMMSCs performed outstanding
capacity of cartilage repair, resulted in the remission of local joint
inflammatory condition, and prevented further articular cartilage damage. The
results demonstrated that the transplantation of BMMSCs in fibrin gel to
osteochondral defect under arthritic condition could effectively stimulate BMMSCs
to exhibit the immunosuppression and cartilage protection capability, as well as
cartilage repair. This study provided a new therapeutic strategy for RA-induced
cartilage injury through the local transplantation of BMMSCs.
PMID- 26414239
TI - An anti-mosquito mixture for domestic use, combining a fertiliser and a chemical
or biological larvicide.
AB - BACKGROUND: Plant saucers are an important larval habitat for Aedes aegypti and
Ae. albopictus in peridomestic situations. Because NPK fertilisers in plant
containers tend to enhance the oviposition of these species, we investigated the
effects of Bacillus thuringiensis var. israelensis, spinosad, pyriproxyfen and
diflubenzuron larvicides in combination with fertiliser on the adult emergence
and fecundity of the mosquitoes coming from plant saucers in controlled
greenhouse experiments. NPK + larvicide (NPK-LAV) treatments were tested on Ae.
aegypti. Each treatment was compared with water and with fertiliser alone on a
total of five houseplants and their saucers. The fertilising treatment was
renewed every 30-45 days. RESULTS: With less than 5% imaginal emergence, the NPK
+ spinosad 0.5% treatment remained effective for 30 days. Both NPK + pyriproxyfen
0.1% and NPK + diflubenzuron 0.25% were effective for 45 days. The average number
of eggs laid in the three treatments was similar to the NPK treatment, indicating
that spinosad, pyriproxyfen and diflubenzuron did not alter the attraction effect
of the fertiliser on egg laying. NPK + pyriproxyfen and NPK + diflubenzuron also
had ovicidal activity and an important impact on the fecundity of the Ae. aegypti
female imagos and the fertility of their eggs. CONCLUSION: The addition of NPK
fertiliser to insecticides can increase larval control of Aedes mosquitoes. This
innovative measure for personal protection, which is harmless for both humans and
animals, would be an additional support for the community-based actions led by
the institutional services for vector control. (c) 2015 Society of Chemical
Industry.
PMID- 26414240
TI - Anti-Melanoma Differentiation-Associated Gene 5 Is Associated With Rapidly
Progressive Lung Disease and Poor Survival in US Patients With Amyopathic and
Myopathic Dermatomyositis.
AB - OBJECTIVE: Clinically amyopathic dermatomyositis (CADM) is a subset of
dermatomyositis (DM) presenting with the characteristic rash of DM without
objective muscle weakness. Asian studies report that anti-melanoma
differentiation-associated gene 5 (anti-MDA-5) autoantibody in CADM is associated
with interstitial lung disease (ILD), particularly rapidly progressive ILD
(RPILD). These associations have not been established in US myositis patients.
The goal of our study was to determine the association of anti-MDA-5 autoantibody
with ILD, RPILD, and survival in US patients with CADM and classic DM. METHODS:
CADM patients were identified in the University of Pittsburgh Myositis Center
Database and matched 1:1 (sex and age) to classic DM controls. Anti-MDA-5 was
measured by serum enzyme-linked immunosorbent assay. Kaplan-Meier, log rank, and
chi-square tests were used for analysis. RESULTS: We identified 61 CADM patients
(62% women, mean age 48.2 years) and 61 classic DM controls (64% women, mean age
44.8 years). The frequencies of anti-MDA-5 positivity, ILD, and RPILD were
similar in the 2 cohorts (MDA-5 positive: CADM 13.1% [8 of 61] and DM 13.1% [8 of
61], ILD positive: CADM 31.1% [19 of 61] and DM 26.2% [16 of 61], and RPILD
positive: CADM 8.2% [5 of 61] and DM 5% [3 of 61]; P = 1, 0.55, and 0.46,
respectively). Anti-MDA-5 positivity was significantly associated with ILD, since
50% of MDA-5-positive subjects (8 of 16) had ILD versus 25.5% of MDA-5-negative
subjects (27 of 106; P = 0.04). Anti-MDA-5 was strongly associated with RPILD (P
< 0.001). Anti-MDA-5-positive patients with ILD had worse baseline pulmonary
function testing variables compared to anti-MDA-5-negative patients. Anti-MDA-5
positivity was significantly associated with poor survival (P = 0.007).
CONCLUSION: Anti-MDA-5 antibody is significantly associated with ILD, RPILD,
worse pulmonary outcome, and survival in US classic DM and CADM patients.
PMID- 26414241
TI - Molecular dynamics simulations of the free and inhibitor-bound cruzain systems in
aqueous solvent: insights on the inhibition mechanism in acidic pH.
AB - The major cysteine protease of Trypanosoma cruzi, cruzain (CRZ), has been
described as a therapeutic target for Chagas' disease, which affects millions of
people worldwide. Thus, a series of CRZ inhibitors has been studied, including a
new competitive inhibitor, Nequimed176 (NEQ176). Nevertheless, the structural and
dynamic basis for CRZ inhibition remains unclear. Hoping to contribute to this
ever-growing understanding of timescale dynamics in the CRZ inhibition mechanism,
we have performed the first study using 100 ns of molecular dynamics (MD)
simulations of two CRZ systems in an aqueous solvent under pH 5.5: CRZ in the apo
form (ligand free) and CRZ complexed to NEQ176. According to the MD simulations,
the enzyme adopts an open conformation in the apo form and a closed conformation
in the NEQ176-CRZ complex. We also suggest that this closed conformation is
related to the hydrogen-bonding interactions between NEQ176 and CRZ, which occurs
through key residues, mainly Gly66, Met68, Asn69, and Leu160. In addition, the
cross-correlation analysis shows evidence of the correlated motions among Ala110
Asp140, Leu160-Gly189, and Glu190-Gly215 subdomains, as well as, the movements
related to Ala1-Thr59 and Asp60-Pro90 regions seem to be crucial for CRZ
activity.
PMID- 26414242
TI - Ultrafast Interfacial Electron and Hole Transfer from CsPbBr3 Perovskite Quantum
Dots.
AB - Recently reported colloidal lead halide perovskite quantum dots (QDs) with
tunable photoluminescence (PL) wavelengths covering the whole visible spectrum
and exceptionally high PL quantum yields (QYs, 50-90%) constitute a new family of
functional materials with potential applications in light-harvesting and
emitting devices. By transient absorption spectroscopy, we show that the high PL
QYs (~79%) can be attributed to negligible electron or hole trapping pathways in
CsPbBr3 QDs: ~94% of lowest excitonic states decayed with a single-exponential
time constant of 4.5 +/- 0.2 ns. Furthermore, excitons in CsPbBr3 QDs can be
efficiently dissociated in the presence of electron or hole acceptors. The half
lives of electron transfer (ET) to benzoquinone and subsequent charge
recombination are 65 +/- 5 ps and 2.6 +/- 0.4 ns, respectively. The half-lives
for hole transfer (HT) to phenothiazine and the subsequent charge recombination
are 49 +/- 6 ps and 1.0 +/- 0.2 ns, respectively. The lack of electron and hole
traps and fast interfacial ET and HT rates are key properties that may enable the
development of efficient lead halide perovskite QDs-based light-harvesting and
emitting devices.
PMID- 26414243
TI - Breg Cells Are Numerically Decreased and Functionally Impaired in Patients With
Systemic Sclerosis.
AB - OBJECTIVE: Breg cells, a regulatory cell subset that produces interleukin-10 (IL
10), play a significant role in suppressing autoimmune responses and preventing
autoimmunity. This study was undertaken to examine the number and function of
Breg cells in patients with systemic sclerosis (SSc), a disease with many
autoantibodies. METHODS: Forty-five patients with SSc (12 with early SSc, 33 with
established disease including 16 with SSc-associated pulmonary fibrosis [PF]), 12
healthy control subjects, and 10 patients with rheumatoid arthritis (RA)
associated PF were studied. The phenotypes of immature/transitional Breg cells
(CD19+CD24(high) CD38(high) ) and memory Breg cells (CD19+CD27+CD24(high) ) were
evaluated by flow cytometry. The function of Breg cells was assessed by measuring
the production of IL-10 after B cell activation. In addition, activation of p38
MAPK and STAT-3 was measured following stimulation of the cells with B cell
receptor (BCR) and Toll-like receptor 9 (TLR-9). RESULTS: Percentages of memory
Breg cells were decreased in patients with early SSc (mean +/- SEM 1.85 +/-
0.38%), those with established SSc (1.6 +/- 0.88%), those with SSc-associated PF
(1.52 +/- 0.17%), and those with RA-associated PF (1.58 +/- 0.26%), compared to
healthy controls (6.3 +/- 0.49%; each P < 0.001). Percentages of transitional
Breg cells were also decreased. Expression of IL-10 by Breg cells after
stimulation with TLR-9 was impaired in patients with SSc, particularly those with
SSc-associated PF. Activation of STAT-3 and p38 MAPK was impaired in naive and
memory B cells from patients with SSc after stimulation with BCR and TLR-9.
Expression of the stimulatory CD19 receptor was increased in B cells and also
increased, to a lesser extent, in Breg cells from patients with SSc compared to
healthy controls. Percentages of memory B cells were decreased in patients with
SSc, particularly in those with SSc-associated PF. CONCLUSION: This is the first
study to demonstrate that Breg cells are phenotypically and functionally impaired
in patients with SSc. Furthermore, in SSc, B cells exhibit impaired p38 MAPK and
STAT-3 activation upon stimulation with BCR and TLR-9. The findings of decreased
numbers of Breg cells along with increased expression of CD19 support the idea of
B cell autoaggression acting as an immunopathogenic mediator in SSc.
PMID- 26414245
TI - Hypothesis test of mediation effect in causal mediation model with high
dimensional continuous mediators.
AB - Causal mediation modeling has become a popular approach for studying the effect
of an exposure on an outcome through a mediator. However, current methods are not
applicable to the setting with a large number of mediators. We propose a testing
procedure for mediation effects of high-dimensional continuous mediators. We
characterize the marginal mediation effect, the multivariate component-wise
mediation effects, and the L2 norm of the component-wise effects, and develop a
Monte-Carlo procedure for evaluating their statistical significance. To
accommodate the setting with a large number of mediators and a small sample size,
we further propose a transformation model using the spectral decomposition. Under
the transformation model, mediation effects can be estimated using a series of
regression models with a univariate transformed mediator, and examined by our
proposed testing procedure. Extensive simulation studies are conducted to assess
the performance of our methods for continuous and dichotomous outcomes. We apply
the methods to analyze genomic data investigating the effect of microRNA miR-223
on a dichotomous survival status of patients with glioblastoma multiforme (GBM).
We identify nine gene ontology sets with expression values that significantly
mediate the effect of miR-223 on GBM survival.
PMID- 26414246
TI - Gene Transfer Strategies to Promote Chondrogenesis and Cartilage Regeneration.
AB - Gene transfer has been used experimentally to promote chondrogenesis and
cartilage regeneration. While it is controversial to apply gene therapy for
nonlethal conditions such as cartilage defect, there is a possibility that the
transfer of therapeutic transgenes may dramatically increase the effectiveness of
cell therapy and reduce the quantity of cells that are needed to regenerate
cartilage. Single or combination of growth factors and transcription factors has
been transferred to mesenchymal stem cells or articular chondrocytes using both
nonviral and viral approaches. The current challenge for the clinical
applications of genetically modified cells is ensuring the safety of gene therapy
while guaranteeing effectiveness. Viral gene delivery methods have been mainstays
currently with enhanced safety features being recently refined. On the other
hand, efficiency has been greatly improved in nonviral delivery. This review
summarizes the history and recent update on the gene transfer to enhance
chondrogenesis from stem cells or articular chondrocytes.
PMID- 26414244
TI - Folic Acid Promotes Recycling of Tetrahydrobiopterin and Protects Against Hypoxia
Induced Pulmonary Hypertension by Recoupling Endothelial Nitric Oxide Synthase.
AB - AIMS: Nitric oxide (NO) derived from endothelial NO synthase (eNOS) has been
implicated in the adaptive response to hypoxia. An imbalance between 5,6,7,8
tetrahydrobiopterin (BH4) and 7,8-dihydrobiopterin (BH2) can result in eNOS
uncoupling and the generation of superoxide instead of NO. Dihydrofolate
reductase (DHFR) can recycle BH2 to BH4, leading to eNOS recoupling. However, the
role of DHFR and eNOS recoupling in the response to hypoxia is not well
understood. We hypothesized that increasing the capacity to recycle BH4 from BH2
would improve NO bioavailability as well as pulmonary vascular remodeling (PVR)
and right ventricular hypertrophy (RVH) as indicators of pulmonary hypertension
(PH) under hypoxic conditions. RESULTS: In human pulmonary artery endothelial
cells and murine pulmonary arteries exposed to hypoxia, eNOS was uncoupled as
indicated by reduced superoxide production in the presence of the nitric oxide
synthase inhibitor, L-(G)-nitro-L-arginine methyl ester (L-NAME). Concomitantly,
NO levels, BH4 availability, and expression of DHFR were diminished under
hypoxia. Application of folic acid (FA) restored DHFR levels, NO bioavailability,
and BH4 levels under hypoxia. Importantly, FA prevented the development of
hypoxia-induced PVR, right ventricular pressure increase, and RVH. INNOVATION: FA
induced upregulation of DHFR recouples eNOS under hypoxia by improving BH4
recycling, thus preventing hypoxia-induced PH. CONCLUSION: FA might serve as a
novel therapeutic option combating PH.
PMID- 26414248
TI - The sadistic trait predicts minimization of intention and causal responsibility
in moral judgment.
AB - The present research tests the hypothesis that specific socially aversive traits
subclinical sadism in particular-are associated with an impaired judgment of
moral wrongness, guilt, and punishment in various moral scenarios manipulating
intent, cause and consequence of harm. In three online studies (total N=1069),
participants completed a battery of tests scaled to assess sadism and the Dark
Triad constructs, then faced different situations involving moral issues
(attempted harm, intentional harm, accidental harm). Study 1 revealed that a
sadistic personality trait was associated with minimization of the importance of
harmful intent in moral judgment. Study 2 showed that a sadistic personality
trait predicted minimization of the importance of causal mechanisms to harmful
consequences in moral judgment. Study 3 showed that these effects were mediated
by enjoyment of cruelty, a characteristic unique to sadists. In the light of
Cushman's (2008) two-process model of moral judgment, this set of studies
provides the first evidence that deficits in the integration of the theory of
mind and causality can be observed in personality traits. The independent
predictive value of sadism highlights that features other than emotional deficits
are essential in explaining impaired moral evaluations.
PMID- 26414247
TI - Elevated carbon dioxide accelerates the spatial turnover of soil microbial
communities.
AB - Although elevated CO2 (eCO2 ) significantly affects the alpha-diversity,
composition, function, interaction and dynamics of soil microbial communities at
the local scale, little is known about eCO2 impacts on the geographic
distribution of micro-organisms regionally or globally. Here, we examined the
beta-diversity of 110 soil microbial communities across six free air CO2
enrichment (FACE) experimental sites using a high-throughput functional gene
array. The beta-diversity of soil microbial communities was significantly (P <
0.05) correlated with geographic distance under both CO2 conditions, but declined
significantly (P < 0.05) faster at eCO2 with a slope of -0.0250 than at ambient
CO2 (aCO2 ) with a slope of -0.0231 although it varied within each individual
site, indicating that the spatial turnover rate of soil microbial communities was
accelerated under eCO2 at a larger geographic scale (e.g. regionally). Both
distance and soil properties significantly (P < 0.05) contributed to the observed
microbial beta-diversity. This study provides new hypotheses for further
understanding their assembly mechanisms that may be especially important as
global CO2 continues to increase.
PMID- 26414250
TI - [In Process Citation].
PMID- 26414251
TI - [In Process Citation].
PMID- 26414252
TI - [In Process Citation].
PMID- 26414249
TI - Is there a domain-general cognitive structuring system? Evidence from structural
priming across music, math, action descriptions, and language.
AB - Cognitive processing in many domains (e.g., sentence comprehension, music
listening, and math solving) requires sequential information to be organized into
an integrational structure. There appears to be some overlap in integrational
processing across domains, as shown by cross-domain interference effects when for
example linguistic and musical stimuli are jointly presented (Koelsch, Gunter,
Wittfoth, & Sammler, 2005; Slevc, Rosenberg, & Patel, 2009). These findings
support theories of overlapping resources for integrational processing across
domains (cfr. SSIRH Patel, 2003; SWM, Kljajevic, 2010). However, there are some
limitations to the studies mentioned above, such as the frequent use of
unnaturalistic integrational difficulties. In recent years, the idea has risen
that evidence for domain-generality in structural processing might also be
yielded though priming paradigms (cfr. Scheepers, 2003). The rationale behind
this is that integrational processing across domains regularly requires the
processing of dependencies across short or long distances in the sequence,
involving respectively less or more syntactic working memory resources (cfr. SWM,
Kljajevic, 2010), and such processing decisions might persist over time. However,
whereas recent studies have shown suggestive priming of integrational structure
between language and arithmetics (though often dependent on arithmetic
performance, cfr. Scheepers et al., 2011; Scheepers & Sturt, 2014), it remains to
be investigated to what extent we can also find evidence for priming in other
domains, such as music and action (cfr. SWM, Kljajevic, 2010). Experiment 1a
showed structural priming from the processing of musical sequences onto the
position in the sentence structure (early or late) to which a relative clause was
attached in subsequent sentence completion. Importantly, Experiment 1b showed
that a similar structural manipulation based on non-hierarchically ordered color
sequences did not yield any priming effect, suggesting that the priming effect is
not based on linear order, but integrational dependency. Finally, Experiment 2
presented primes in four domains (relative clause sentences, music, mathematics,
and structured descriptions of actions), and consistently showed priming within
and across domains. These findings provide clear evidence for domain-general
structural processing mechanisms.
PMID- 26414253
TI - [In Process Citation].
PMID- 26414254
TI - [In Process Citation].
PMID- 26414255
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PMID- 26414256
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PMID- 26414257
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PMID- 26414258
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PMID- 26414259
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PMID- 26414262
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PMID- 26414263
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PMID- 26414264
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PMID- 26414267
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PMID- 26414269
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PMID- 26414268
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PMID- 26414271
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PMID- 26414272
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PMID- 26414273
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PMID- 26414275
TI - [In Process Citation].
PMID- 26414274
TI - [In Process Citation].
PMID- 26414277
TI - Update on the current methods for the diagnosis and treatment of severe childhood
asthma.
AB - The level of asthma control is the key outcome towards which asthma management is
evaluated. The majority of children with asthma can obtain adequate control of
symptoms through avoidance of triggering factors and/or with the help of low to
moderate doses of current available medications. However, there is still a group
of children with poor symptom control despite intensive treatment. The current
review will provide an overview of a standardized approach to characterize this
heterogeneous group of severely sick children. Factors that attenuate the effect
of the prescribed treatment and make asthma difficult to treat are discussed. In
addition, the usefulness of current methods of assessing asthma severity,
pulmonary function, allergy and airway inflammation is also described. Finally,
an overview of therapeutic options for children with severe asthma is provided.
PMID- 26414276
TI - Microgravity Reduces the Differentiation and Regenerative Potential of Embryonic
Stem Cells.
AB - Mechanical unloading in microgravity is thought to induce tissue degeneration by
various mechanisms, including inhibition of regenerative stem cell
differentiation. To address this hypothesis, we investigated the effects of
microgravity on early lineage commitment of mouse embryonic stem cells (mESCs)
using the embryoid body (EB) model of tissue differentiation. We found that
exposure to microgravity for 15 days inhibits mESC differentiation and expression
of terminal germ layer lineage markers in EBs. Additionally, microgravity
unloaded EBs retained stem cell self-renewal markers, suggesting that mechanical
loading at Earth's gravity is required for normal differentiation of mESCs.
Finally, cells recovered from microgravity-unloaded EBs and then cultured at
Earth's gravity showed greater stemness, differentiating more readily into
contractile cardiomyocyte colonies. These results indicate that mechanical
unloading of stem cells in microgravity inhibits their differentiation and
preserves stemness, possibly providing a cellular mechanistic basis for the
inhibition of tissue regeneration in space and in disuse conditions on earth.
PMID- 26414278
TI - Fabrication of Tunable, High-Refractive-Index Titanate-Silk Nanocomposites on the
Micro- and Nanoscale.
AB - The combination of water-based titanate nanosheets dispersion and silk fibroin
solution allows the realization of a versatile nanocomposite. Different
fabrication techniques can be easily applied on these nanocomposites to
manipulate the end form of these materials on the micro- and nanoscale. Easy
tunability of the refractive index from n = 1.55 up to n = 1.97 is achieved,
making it attractive for flexible, biopolymer-based optical devices.
PMID- 26414279
TI - "Keep your brain fit!" Effectiveness of a psychoeducational intervention on
cognitive functioning in healthy adults: A randomised controlled trial.
AB - A psychoeducational intervention (Keep your brain fit!) was designed for the
middle-aged and older working population. The intervention focuses on increasing
knowledge and awareness about cognitive ageing and teaching strategies to cope
with cognitive changes. The primary aim of this study was to investigate the
effectiveness of the e-health intervention in terms of subjective cognitive
functioning. As secondary aims, objective cognitive functioning and psychological
well-being were also measured. A randomised controlled trial that included people
aged 40 to 65 years was conducted. A maximum of 4 weeks was allowed to complete
the intervention. The outcome measures were obtained from an online test battery
that was administered at baseline, post-test and at 4-week follow-up. A total of
376 participants completed the whole study. After the intervention, the
experimental group reported more feelings of stability concerning memory
functioning and perceived greater locus of control over memory compared to the
control group. These effects were maintained at the 4-week follow-up. Taking into
account the relatively low costs and easy accessibility of this e-health
intervention, we consider the programme to be a valuable contribution to public
healthcare interventions for middle-aged and older adults.
PMID- 26414280
TI - Uterine artery embolization using progressively larger calibrated gelatin sponge
particles.
AB - PURPOSE: To assess the effectiveness and safety of uterine artery embolization
(UAE) using progressively larger calibrated gelatin sponge particles for
symptomatic uterine fibroids. MATERIAL AND METHODS: Thirty patients with
symptomatic uterine fibroids underwent UAE. Calibrated gelatin sponge particles
were used in all patients, beginning with 355-500 MUm particles, progressively
increasing to 500-710 MUm and finally to 710-1000 MUm particles. Changes in
tumor, uterine volume, and tumor infarction rate were assessed using pelvic
magnetic resonance imaging (MRI). The level of complication, improvement of
clinical symptoms, and Uterine Fibroid Symptom and Quality of Life (UFS-QOL)
score were assessed. RESULTS: MR imaging revealed the mean largest tumor volume
reduction was 56.23 +/- 16.25% at three months and 72.61 +/- 14.47% at 12 months
after the procedure. 100% infarction of the dominant fibroids was 91.27 +/- 5.02%
at three months and 96 +/- 5.20% at 12 months after the procedure. Menorrhagia
improved markedly in all 23 patients. Bulk-related symptoms improved in 12
(92.30%) of 13 patients. The baseline UFS-QOL score was 43.13 and improved to
11.88 (p < 0.001). No major complications were observed. CONCLUSION: UAE using
progressively larger calibrated gelatin sponge particles is an effective and safe
treatment for symptomatic uterine fibroids.
PMID- 26414281
TI - Comments on Auble et al. Regarding Hypopituitarism in Pediatric Survivors of
Inflicted Traumatic Brain Injury.
PMID- 26414282
TI - Survey of Attitudes and Ethical Concerns Related to Gene Therapy Among Medical
Students and Postgraduates in China.
AB - Gene therapy is becoming an important treatment modality for gravely ill
patients, and today's medical students and postgraduates are both potential
consumers and future providers of gene therapy. Therefore, their attitudes and
concerns about gene therapy may directly influence its long-term development and
implementation in the clinic. We performed a cross-sectional survey of medical
students and postgraduates at West China Medical School of Sichuan University. A
custom-designed questionnaire was distributed to 600 students, and 579 were valid
(96.98% response). Most respondents (84.46%) indicated little prior knowledge
about gene therapy. The proportion of respondents considering gene therapy as
acceptable ranged from 63.73% for serious illness to 17.72% for genetic
enhancement. Adverse side effects were the most frequent concern among
respondents when asked to imagine that they would receive gene therapy to treat a
severe brain-related illness. These results suggest that medical students in
China consider gene therapy's acceptability to be rather low, and are most
concerned about its adverse side effects.
PMID- 26414283
TI - Comparative Evaluation of the Vector Competence of Four South American
Populations of the Rhipicephalus sanguineus Group for the Bacterium Ehrlichia
canis, the Agent of Canine Monocytic Ehrlichiosis.
AB - This study compared the vector competence of four populations of Rhipicephalus
sanguineus group ticks for the bacterium Ehrlichia canis, the agent of canine
monocytic ehrlichiosis (CME). Ticks (larvae and nymphs) from the four populations
one from Sao Paulo state, southeastern Brazil (BSP), one from Rio Grande do Sul
state, southern Brazil (BRS), one from Argentina (ARG), and one from Uruguay
(URU)-were exposed to E. canis infection by feeding on dogs that were
experimentally infected with E. canis. Engorged ticks (larvae and nymphs) were
allowed to molt to nymphs and adults, respectively, which were tested by
molecular analysis (E. canis-specific PCR assay) and used to infest naive dogs.
Through infestation of adult ticks on naive dogs, after nymphal acquisition
feeding on E. canis-infected dogs, only the BSP population was shown to be
competent vectors of E. canis, i.e., only the dogs infested with BSP adult ticks
developed clinical illness, seroconverted to E. canis, and yielded E. canis DNA
by PCR. This result, demonstrated by two independent replications, is congruent
with epidemiological data, since BSP ticks were derived from Sao Paulo state,
Brazil, where CME is highly endemic. On the other hand, BRS, ARG, and URU ticks
were derived from a geographical region (South America southern cone) where CME
has never been properly documented. Molecular analysis of unfed adults at 30 days
post molting support these transmission results, since none of the BRS, ARG, and
URU ticks were PCR positive, whereas 1% of the BSP nymphs and 31.8% of the BSP
adults contained E. canis DNA. We conclude that the absence or scarcity of cases
of CME due to E. canis in the South America southern cone is a result of vector
incompetence of the R. sanguineus group ticks that prevail on dogs in this part
of South America.
PMID- 26414284
TI - Diagnosis and Treatment of Left-Sided Prosthetic Paravalvular Regurgitation.
AB - Paravalvular leak (PVL) is a complication related to the surgical implantation of
left-sided prosthetic valves. The prevalence of paravalvular regurgitation ranges
between 5 and 20%. Left-sided prosthetic paravalvular regurgitation presents with
a wide constellation of signs and symptoms ranging from asymptomatic murmur to
heart failure, hemolysis and cardiac cachexia. Echocardiography plays a key role
in imaging the PVL and can help in guiding the closure procedure with both
transesophageal and intracardiac probes. Transcatheter closure of paravalvular
regurgitations is an appealing prospect.
PMID- 26414286
TI - A vegetable oil-based organogel for use in pH-mediated drug delivery.
AB - Organogels prepared with vegetable oils as the liquid organic phase present an
excellent platform for the controlled delivery of hydrophobic guest molecules. We
disclose a graft copolymer comprised of a poly(L-serine) backbone linked to
alkane side-chains by hydrolytically susceptible ester bonds, that is capable of
gelating edible safflower oil. The thermoresponsive organogel formed, which is
non-cytotoxic, is capable of withholding guest molecules before undergoing
targeted disassembly upon incubation in solutions of acidic pH, permitting the
directed release of payload molecules. The presented material offers an extremely
promising candidate for the controlled delivery of hydrophobic agents within
acidic environments, such as cancer tumour sites.
PMID- 26414288
TI - Agreement between High School Athletes and Their Parents on Reporting Athletic
Events and Concussion Symptoms.
AB - An enhanced understanding of agreement levels between adolescents and parents for
reporting athletic events and symptoms can help inform surveillance systems as
well as clinical and epidemiological investigations of sports-related
concussions. We sought to quantify agreement levels between high school athletes
and parents for reporting: (1) number of games; (2) number of practices; (3)
occurrence of an injury resulting in any concussion symptoms; and (4) presence of
each specific symptom on the date of that injury among high school boys' football
and girls' soccer athletes playing in Autumn 2012 in Washington State. There was
substantial agreement on reporting the number of athletic events. Agreement
levels were greater for games (kappa = 0.82; 95% confidence interval [CI]: 0.79
0.85 in boys' football; kappa = 0.75; 95% CI: 0.72-0.79 in girls' soccer) than
for practices (kappa = 0.64; 95% CI: 0.62-0.67 in boys' football; kappa = 0.65;
95% CI: 0.62-0.67 in girls' soccer). There was moderate to substantial agreement
on the occurrence of injury resulting in any concussion symptoms; however,
agreement on the presence and severity of each symptom varied from poor to almost
perfect. Overall, athletes reported greater severity of symptoms than parents
did; notably, no difference in mean symptom scores was found when the athlete had
a history of concussion. Agreement levels were greater when information was
ascertained within 1 week of injury than when it was obtained later than 1 week.
Including both athletes' and parents' reports of sports-related events and
ascertaining information as soon as possible after injury are important
considerations in designing injury surveillance systems.
PMID- 26414290
TI - Application of the continual reassessment method to dose-finding studies in
regional anesthesia: an estimate of the ED95 dose for 0.5% bupivacaine for
ultrasound-guided supraclavicular block: erratum.
PMID- 26414287
TI - Identification of Circulating Biomarker Candidates for Hepatocellular Carcinoma
(HCC): An Integrated Prioritization Approach.
AB - Hepatocellular carcinoma (HCC) is the world's third most widespread cancer.
Currently available circulating biomarkers for this silently progressing
malignancy are not sufficiently specific and sensitive to meet all clinical
needs. There is an imminent and pressing need for the identification of novel
circulating biomarkers to increase disease-free survival rate. In order to
facilitate the selection of the most promising circulating protein biomarkers, we
attempted to define an objective method likely to have a significant impact on
the analysis of vast data generated from cutting-edge technologies. Current study
exploits data available in seven publicly accessible gene and protein databases,
unveiling 731 liver-specific proteins through initial enrichment analysis.
Verification of expression profiles followed by integration of proteomic
datasets, enriched for the cancer secretome, filtered out 20 proteins including 6
previously characterized circulating HCC biomarkers. Finally, interactome
analysis of these proteins with midkine (MDK), dickkopf-1 (DKK-1), current
standard HCC biomarker alpha-fetoprotein (AFP), its interacting partners in
conjunction with HCC-specific circulating and liver deregulated miRNAs target
filtration highlighted seven novel statistically significant putative biomarkers
including complement component 8, alpha (C8A), mannose binding lectin (MBL2),
antithrombin III (SERPINC1), 11beta-hydroxysteroid dehydrogenase type 1
(HSD11B1), alcohol dehydrogenase 6 (ADH6), beta-ureidopropionase (UPB1) and
cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6). Our proposed
methodology provides a swift assortment process for biomarker prioritization that
eventually reduces the economic burden of experimental evaluation. Further
dedicated validation studies of potential putative biomarkers on HCC patient
blood samples are warranted. We hope that the use of such integrative secretome,
interactome and miRNAs target filtration approach will accelerate the selection
of high-priority biomarkers for other diseases as well, that are more amenable to
downstream clinical validation experiments.
PMID- 26414289
TI - Differences in pteridine urinary levels in patients with malignant and benign
ovarian tumors in comparison with healthy individuals.
AB - Pteridines belong to a class of fluorescent metabolites that are excreted by
humans in urine and their concentrations can reflect various pathophysiological
states. We quantified the differences in urinary pteridine levels in patients
with malignant and benign ovarian tumors and in healthy individuals. Urine
samples were centrifuged and supernatants were oxidized by MnO2 before analysis.
Levels of neopterin, biopterin, and pterin were assessed by fluorescence analysis
of human urine after HPLC separation. We have revealed that the median neopterin
levels were higher in urine samples from patients with malignant (0.226
MUmol/mmol creatinine) and benign ovarian tumors (0.150 MUmol/mmol creatinine)
than in healthy subjects (0.056 MUmol/mmol creatinine). The median neopterin
levels of patients with malignant tumors were higher (1.5-times) than in patients
with benign tumors. The median biopterin level in urine of patients with benign
ovarian tumors (0.268 MUmol/mmol creatinine) was found to be very close to the
level in patients with malignant ovarian tumors (0.239 MUmol/mmol creatinine),
and both were higher than in healthy samples (0.096 MUmol/mmol creatinine). The
levels of urine pterin followed a pattern similar to neopterin levels for both
ovarian tumors, but their concentrations were about three times lower than
neopterin levels.
PMID- 26414291
TI - Relativistic Force Field: Parametrization of (13)C-(1)H Nuclear Spin-Spin
Coupling Constants.
AB - Previously, we reported a reliable DU8 method for natural bond orbital (NBO)
aided parametric scaling of Fermi contacts to achieve fast and accurate
prediction of proton-proton spin-spin coupling constants (SSCC) in (1)H NMR. As
sophisticated NMR experiments for precise measurements of carbon-proton SSCCs are
becoming more user-friendly and broadly utilized by the organic chemistry
community to guide and inform the process of structure determination of complex
organic compounds, we have now developed a fast and accurate method for computing
(13)C-(1)H SSCCs. Fermi contacts computed with the DU8 basis set are scaled using
selected NBO parameters in conjunction with empirical scaling coefficients. The
method is optimized for inexpensive B3LYP/6-31G(d) geometries. The parametric
scaling is based on a carefully selected training set of 274 ((3)J), 193 ((2)J),
and 143 ((1)J) experimental (13)C-(1)H spin-spin coupling constants reported in
the literature. The DU8 basis set, optimized for computing Fermi contacts, which
by design had evolved from optimization of a collection of inexpensive 3-21G*, 4
21G, and 6-31G(d) bases, offers very short computational (wall) times even for
relatively large organic molecules containing 15-20 carbon atoms. The most
informative SSCCs for structure determination, i.e., (3)J, were computed with an
accuracy of 0.41 Hz (rmsd). The new unified approach for computing (1)H-(1)H and
(13)C-(1)H SSCCs is termed "DU8c".
PMID- 26414292
TI - Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current
Estimates and Limitations.
AB - RATIONALE: Reducing the global burden of sepsis, a recognized global health
challenge, requires comprehensive data on the incidence and mortality on a global
scale. OBJECTIVES: To estimate the worldwide incidence and mortality of sepsis
and identify knowledge gaps based on available evidence from observational
studies. METHODS: We systematically searched 15 international citation databases
for population-level estimates of sepsis incidence rates and fatality in adult
populations using consensus criteria and published in the last 36 years.
MEASUREMENTS AND MAIN RESULTS: The search yielded 1,553 reports from 1979 to
2015, of which 45 met our criteria. A total of 27 studies from seven high-income
countries provided data for metaanalysis. For these countries, the population
incidence rate was 288 (95% confidence interval [CI], 215-386; tau = 0.55) for
hospital-treated sepsis cases and 148 (95% CI, 98-226; tau = 0.99) for hospital
treated severe sepsis cases per 100,000 person-years. Restricted to the last
decade, the incidence rate was 437 (95% CI, 334-571; tau = 0.38) for sepsis and
270 (95% CI, 176-412; tau = 0.60) for severe sepsis cases per 100,000 person
years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during
this period. There were no population-level sepsis incidence estimates from lower
income countries, which limits the prediction of global cases and deaths.
However, a tentative extrapolation from high-income country data suggests global
estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with
potentially 5.3 million deaths annually. CONCLUSIONS: Population-level
epidemiologic data for sepsis are scarce and nonexistent for low- and middle
income countries. Our analyses underline the urgent need to implement global
strategies to measure sepsis morbidity and mortality, particularly in low- and
middle-income countries.
PMID- 26414294
TI - Comparison of Physician-Based and Patient-Based Criteria for the Diagnosis of
Fibromyalgia.
AB - OBJECTIVE: The American College of Rheumatology (ACR) 2010 preliminary
fibromyalgia diagnostic criteria require symptom ascertainment by physicians. The
2011 survey or research modified ACR criteria use only patient self-report. We
compared physician-based (MD) (2010) and patient-based (PT) (2011) criteria and
criteria components to determine the degree of agreement between criteria
methodology. METHODS: We studied prospectively collected, previously unreported
rheumatology practice data from 514 patients and 30 physicians in the ACR 2010
study. We evaluated the widespread pain index, polysymptomatic distress (PSD)
scale, tender point count (TPC), and fibromyalgia diagnosis using 2010 and 2011
rules. Bland-Altman 95% limits of agreement (LOA), kappa statistic, Lin's
concordance coefficient, and the area under the receiver operating curve (ROC)
were used to measure agreement and discrimination. RESULTS: MD and PT diagnostic
agreement was substantial (83.4%, kappa = 0.67). PSD scores differed slightly
(12.3 MD, 12.8 PT; P = 0.213). LOA for PSD were -8.5 and 7.7, with bias of -0.42.
The TPC was strongly associated with both the MD (r = 0.779) and PT PSD scales (r
= 0.702). CONCLUSION: There was good agreement in MD and PT fibromyalgia
diagnosis and other measures among rheumatology patients. Low bias scores
indicate consistent results for physician and patient measures, but large values
for LOA indicate many widely discordant pairs. There is acceptable agreement in
diagnosis and PSD for research, but insufficient agreement for clinical decisions
and diagnosis. We suggest adjudication of symptom data by patients and
physicians, as recommended by the 2010 ACR criteria.
PMID- 26414295
TI - Semiconductor Behavior of a Three-Dimensional Strontium-Based Metal-Organic
Framework.
AB - The self-assembly of a three-dimensional strontium-based metal-organic framework
[Sr(Hbtc)(H2O)]n (1) was achieved through the reaction of Sr(NO3)2 with a 1,2,4
benzenetricarboxylic acid (1,2,4-H3btc) ligand under hydrothermal conditions.
This Sr-based metal-organic framework exhibits remarkable semiconducting
behavior, as evidenced by theoretical calculations and experimental measurements.
Temperature-dependent DC conductivity, near-room-temperature AC conductivity,
diffuse reflection spectra, and photoluminescence spectra provide strong proof
that compound 1 shows a band gap of 2.3 eV, which is comparable to that for other
commonly available semiconducting materials (e.g., CdSe, CdTe, ZnTe, GaP, etc.).
The optimized molecular structure and electronic properties (density of states
and band gap energy) of 1 were calculated using density functional theory, and
the results are consistent with experimental findings. This is the first report
on the semiconducting properties of a strontium-based MOF, which will pave the
way for further studies in semiconducting MOFs with interesting potential
applications in optoelectronic devices.
PMID- 26414296
TI - Investigation of denitrifying microbial communities within an agricultural
drainage system fitted with low-grade weirs.
AB - Enhancing wetland characteristics in agricultural drainage ditches with the use
of low-grade weirs, has been identified as a best management practice (BMP) to
mitigate nutrient runoff from agriculture landscapes. A major objective of
utilizing low-grade weirs as a BMP includes fostering environments suitable for
the biogeochemical removal of nitrogen via denitrification. This study examined
the spatial resolution of microbial communities involved in denitrification in
agricultural drainage systems fitted with low-grade weirs. Appropriate sampling
scales of microbial communities were investigated using 16S rRNA and
denitrification functional genes nosZ, nirS, and nirK via quantitative polymerase
chain reaction (qPCR) and terminal-restriction fragment length polymorphism (T
RFLP) analysis. Genes 16S rRNA, nosZ, and nirS were all successfully detected in
soil samples, while nirK was below the detection limit throughout the study.
Utilizing a combination of three sampling regimes (management, reach, catchment)
was found to be effective in capturing microbial community patterns, as ANOVA
results revealed nosZ gene abundance was significantly greater at the management
rather than reach scale (p = 0.045; F = 3.311), although, no significant
differences were observed in 16S rRNA or nirS between sampling scales (p > 0.05).
A Pearson correlation matrix confirmed that 16S rRNA and nosZ gene abundances
were positively correlated with soil carbon (C), nitrogen (N), and moisture,
while nirS abundance was only positively correlated with soil C and soil
moisture. This highlights the potential for wetland-like characteristics to be
recovered in agricultural drainage systems, as weir proximity is observed to
enhance soil moisture and conditions for N remediation. This study provides the
basis for additional investigations of these unique environments in the
Mississippi Alluvial Valley and a starting point for adaptive management to
enhance agricultural drainage systems for microbial communities towards nutrient
remediation goals.
PMID- 26414297
TI - Surface analysis of pilot distribution system pipe autopsies: The relationship of
organic and inorganic deposits to input water quality.
AB - Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) surface analysis was
conducted to characterise deposits in polyethylene pipes used in a novel pilot
water distribution system (PDS). The system consisted of four (4) parallel
distribution systems receiving water from different treatment processes, ranging
from conventional coagulation through to an advanced membrane filtration system.
After two years of operation, the distribution system was shut down and samples
of pipe were collected for autopsy analysis. Inlet and outlet samples from each
PDS were collected for purpose of comparison. ToF-SIMS was used to assess
chemical differences in surface biofilm accumulation and particulate deposition,
which resulted as a consequence of the treatment method and operational mode of
each system. These data supplemented previously collected bacteriological and
chemical water quality data. Results from the inorganic analysis of the pipes
were consistent with corrosion and contamination events that occurred upstream in
the corresponding treatment systems. Principal component analysis of data on
organic constituents showed oxygen and nitrogen containing fragments were
associated with the treatment inlet and outlet samples. These types of signals
can often be ascribed to biofilm polysaccharides and proteins. A trend was
observed when comparing samples from the same PDS, showing an association of
lower molecular weight (MW) organic fragments with the inlet and higher MW
organic fragments with the outlet samples.
PMID- 26414293
TI - Perspective on Adeno-Associated Virus Capsid Modification for Duchenne Muscular
Dystrophy Gene Therapy.
AB - Duchenne muscular dystrophy (DMD) is a X-linked, progressive childhood myopathy
caused by mutations in the dystrophin gene, one of the largest genes in the
genome. It is characterized by skeletal and cardiac muscle degeneration and
dysfunction leading to cardiac and/or respiratory failure. Adeno-associated virus
(AAV) is a highly promising gene therapy vector. AAV gene therapy has resulted in
unprecedented clinical success for treating several inherited diseases. However,
AAV gene therapy for DMD remains a significant challenge. Hurdles for AAV
mediated DMD gene therapy include the difficulty to package the full-length
dystrophin coding sequence in an AAV vector, the necessity for whole-body gene
delivery, the immune response to dystrophin and AAV capsid, and the species
specific barriers to translate from animal models to human patients. Capsid
engineering aims at improving viral vector properties by rational design and/or
forced evolution. In this review, we discuss how to use the state-of-the-art AAV
capsid engineering technologies to overcome hurdles in AAV-based DMD gene
therapy.
PMID- 26414298
TI - Effect of residual monomer from polyacrylamide on head lettuce grown in peat
substrate.
AB - The paper investigates the migration of the acrylamide monomer (AMD) to lettuce
chosen as a test plant growing in an organic medium (peat substrate).
Polyacrylamide (PAM)-based flocculant added to the growing medium contained no
more than 1000 mg kg(-1) of AMD. Plants were grown with varied doses of PAM
preparation (0.5-3.0 mg dm(-3) of peat substrate) to compare the results with the
control sample. The determination of AMD content, chlorophyll content, weight of
the lettuce head, and also analysis of macro- and micro-elements in lyophilised
test material was made under the same analytical conditions. The results showed
that lettuce plants absorb AMD to the leaves from the peat substrate. The AMD
uptake has a negative impact on the growth of lettuce. It reduces the average
fresh weight of heads and destabilises the mineral composition of the plant.
Therefore, concern related to the transfer risk of the residual AMD from sludge
used for organic fertilisation of edible plants still remains a crucial question
from a food and consumer safety point of view. To ensure consumer safety, the
fate of the AMD following the application of PAM to cropland should be carefully
monitored in the whole food chain.
PMID- 26414299
TI - Improving Diagnosis in Health Care: Highlights of a Report From the National
Academies of Sciences, Engineering, and Medicine.
PMID- 26414300
TI - A tale of two paralogs: human Transformer2 proteins with differential RNA-binding
affinities.
AB - The Transformer2 (Tra2) proteins in humans are homologues of the Drosophila Tra2
protein. One of the two RNA-binding paralogs, Tra2beta, has been very well
studied over the past decade, but not much is known about Tra2alpha. It was very
recently shown that the two proteins demonstrate the phenomenon of paralog
compensation. Here, we provide a structural basis for this genetic backup
circuit, using molecular modelling and dynamics studies. We show that the two
proteins display similar binding specificities, but differential affinities to a
short GAA-rich RNA stretch. Starting from the 6-nucleotide RNA in the solution
structure, close to 4000 virtual mutations were modelled on RNA and the domain
RNA interactions were studied after energy minimisation to convergence.
Separately, another known 13-nucleotide stretch was docked and the domain-RNA
interactions were observed through a 100-ns dynamics trajectory. We have also
demonstrated the 'compensatory' mechanism at the level of domains in one of the
domain repeat-containing RNA-binding proteins.
PMID- 26414301
TI - Online interferometric study of viscoelastic rupture and necking deformation of
as-spun (iPP) fibres due to creep process.
AB - Creep deformation under constant load leads to rupture when the polymer chains
can no longer separate and accommodate the load. This fracture phenomenon is
investigated interferometrically. The creep behaviour of as-spun isotactic
Polypropylene (iPP) fibres is studied at different stresses, different initial
lengths and different radii. The creep rate, which defines the velocity of the
creep deformation and the dimensional stability of the material, is studied. The
failure time and stress of iPP due to creep process is determined. The necking
deformation was in situ detected during creep process. The mean refractive
indices (n(P) andn?) profiles of iPP fibres were determined at different
positions along the fibre axis before and after necking. The relation between the
creep behaviour and different optical and structural parameters is investigated.
Microinterferograms are given for illustration.
PMID- 26414302
TI - Conducting Polymers for Neural Prosthetic and Neural Interface Applications.
AB - Neural-interfacing devices are an artificial mechanism for restoring or
supplementing the function of the nervous system, lost as a result of injury or
disease. Conducting polymers (CPs) are gaining significant attention due to their
capacity to meet the performance criteria of a number of neuronal therapies
including recording and stimulating neural activity, the regeneration of neural
tissue and the delivery of bioactive molecules for mediating device-tissue
interactions. CPs form a flexible platform technology that enables the
development of tailored materials for a range of neuronal diagnostic and
treatment therapies. In this review, the application of CPs for neural prostheses
and other neural interfacing devices is discussed, with a specific focus on
neural recording, neural stimulation, neural regeneration, and therapeutic drug
delivery.
PMID- 26414303
TI - Fabrication and characterization of artificial miniaturized insect compound eyes
for imaging.
AB - Polystyrene (PS) microspheres are synthesized by dispersion polymerization, and a
close-packed two-dimensional (2D) array of the PS microspheres is formed by the
self-assembly method through dip drawing under magnetic stirring. This array is
then used to fabricate a 2D polydimethylsiloxane concave mold by soft
lithography. The mold is employed to produce convex polymethylmethacrylate-based
compound eye-replicating films of different hemispherical heights by
thermopressing. The optical properties of the ommatidia on these biomimetic
compound eye-replicating films are investigated, and the films are used with a
charge-coupled device camera to construct a biomimetic visual system. The visual
distance and field of view of this system are measured. The film with the
greatest hemispherical height results in the biomimetic visual system with the
highest visual distance and the widest field of view. In addition, it is found
that the quality of the optical images is not dependent on the hemispherical
height of the biomimetic films. The ability of the biomimetic visual system to
detect moving object in real time is also studied.
PMID- 26414304
TI - Ultrasound-Guided Renal Access for Percutaneous Nephrolithotomy: A Description of
Three Novel Ultrasound-Guided Needle Techniques.
AB - Ultrasound-guided renal access for percutaneous nephrolithotomy (PCNL) is a safe,
effective, and low-cost procedure commonly performed worldwide, but a technique
underutilized by urologists in the United States. The purpose of this article is
to familiarize the practicing urologist with methods for ultrasound guidance for
percutaneous renal access. We discuss two alternative techniques for gaining
renal access for PCNL under ultrasound guidance. We also describe a novel
technique of using the puncture needle to reposition residual stone fragments to
avoid additional tract dilation. With appropriate training, ultrasound-guided
renal access for PCNL can lead to reduced radiation exposure, accurate renal
access, and excellent stone-free success rates and clinical outcomes.
PMID- 26414305
TI - What automaticity deficit? Activation of lexical information by readers with
dyslexia in a rapid automatized naming Stroop-switch task.
AB - Reading fluency is often predicted by rapid automatized naming (RAN) speed, which
as the name implies, measures the automaticity with which familiar stimuli (e.g.,
letters) can be retrieved and named. Readers with dyslexia are considered to have
less "automatized" access to lexical information, reflected in longer RAN times
compared with nondyslexic readers. We combined the RAN task with a Stroop-switch
manipulation to test the automaticity of dyslexic and nondyslexic readers'
lexical access directly within a fluency task. Participants named letters in 10 *
4 arrays while eye movements and speech responses were recorded. Upon fixation,
specific letter font colors changed from black to a different color, whereupon
the participant was required to rapidly switch from naming the letter to naming
the letter color. We could therefore measure reading group differences on
"automatic" lexical processing, insofar as it was task-irrelevant. Readers with
dyslexia showed obligatory lexical processing and a timeline for recognition that
was overall similar to typical readers, but a delay emerged in the output
(naming) phase. Further delay was caused by visual-orthographic competition
between neighboring stimuli. Our findings outline the specific processes involved
when researchers speak of "impaired automaticity" in dyslexic readers' fluency,
and are discussed in the context of the broader literature in this field.
PMID- 26414306
TI - Molecular Catalysis of O2 Reduction by Iron Porphyrins in Water: Heterogeneous
versus Homogeneous Pathways.
AB - Despite decades of active attention, important problems remain pending in the
catalysis of dioxygen reduction by iron porphyrins in water in terms of
selectivity and mechanisms. This is what happens, for example, for the
distinction between heterogeneous and homogeneous catalysis for soluble
porphyrins, for the estimation of H2O2/H2O product selectivity, and for the
determination of the reaction mechanism in the two situations. With water-soluble
iron tetrakis(N-methyl-4-pyridyl)porphyrin as an example, procedures are
described that allow one to operate this distinction and determine the H2O2/H2O
product ratio in each case separately. It is noteworthy that, despite the weak
adsorption of the iron(II) porphyrin on the glassy carbon electrode, the
contribution of the adsorbed complex to catalysis rivals that of its solution
counterpart. Depending on the electrode potential, two successive catalytic
pathways have been identified and characterized in terms of current-potential
responses and H2O2/H2O selectivity. These observations are interpreted in the
framework of the commonly accepted mechanism for catalytic reduction of dioxygen
by iron porphyrins, after checking its compatibility with a change of oxygen
concentration and pH. The difference in intrinsic catalytic reactivity between
the catalyst in the adsorbed state and in solution is also discussed. The role of
heterogeneous catalysis with iron tetrakis(N-methyl-4-pyridyl)porphyrin has been
overlooked in previous studies because of its water solubility. The main
objective of the present contribution is therefore to call attention, by means of
this emblematic example, to such possibilities to reach a correct identification
of the catalyst, its performances, and reaction mechanism. This is a question of
general interest, so that reduction of dioxygen remains a topic of high
importance in the context of contemporary energy challenges.
PMID- 26414308
TI - The Beginning Psychotherapist and Borderline Personality Disorder: Basic
Treatment Principles and Clinical Foci.
AB - Borderline personality disorder is a prevalent psychopathology; thus, most
graduate students in psychology, residents in psychiatry, and early career
clinicians will encounter patients with this disorder in the course of their
training or initial professional practice. This paper provides clear and concise
guidelines for conducting treatment geared toward the clinician's developmental
level. It builds upon the knowledge and skills that are typically acquired during
graduate education and training to provide an accessible framework for
undertaking psychotherapy with patients who have borderline personality disorder.
This paper draws upon common psychotherapeutic factors and existing evidence
based treatments for the disorder to identify principals and interventions that
are likely to contribute to therapeutic action. It uses behavioral, cognitive,
and psychodynamic interventions to address the patient's multidimensional
psychopathology. This approach offers a coherent and integrated treatment
framework for the beginning psychotherapy practitioner.
PMID- 26414309
TI - Intensive Individual and Group Cognitive Behavioural Therapy for Obsessive
Compulsive Disorder.
AB - Whilst there is good evidence to show intensive individual therapy can be
effective for obsessive-compulsive disorder (OCD), this treatment can be
challenging to deliver for therapists in the National Health Service (NHS). We
report on a novel means of delivering intensive cognitive behavioural therapy
(CBT) by combining it with group work, which allowed therapists to offer each
other mutual support and permitted patients to gain the interpersonal benefits of
working with others. This case study describes the combined intensive individual
and group CBT programme for a 46-year-old woman with OCD. This treatment took
place within a community mental health team within outer London. Following
treatment, the client showed significant improvements in symptoms. This creative
method for treating OCD as part of routine clinical practice may be beneficial
for therapists to feel supported, for reduction in clinicians' time in treatment,
and for clients to benefit from a group experience.
PMID- 26414307
TI - The roles of oxidative stress, endoplasmic reticulum stress, and autophagy in
aldosterone/mineralocorticoid receptor-induced podocyte injury.
AB - Podocytes play an important role in the pathogenesis and progression of
glomerulosclerosis. Recent studies indicate that aldosterone/mineralocorticoid
receptor (MR) is a major contributor of chronic kidney disease (CKD) progression.
Aldosterone/MR induces glomerular podocyte injury, causing the disruption of the
glomerular filtration barrier and proteinuria. The present study investigated the
mechanisms by which aldosterone/MR mediated podocyte injury, focusing on the
involvement of oxidative stress, endoplasmic reticulum (ER) stress, and
autophagy. We observed that aldosterone/MR induced ER stress and podocyte injury
both in vivo and in vitro. Blockade of ER stress significantly reduced
aldosterone/MR-induced podocyte injury. In addition, we found that ER stress
induced podocyte injury was mediated by CCAAT/enhancer-binding protein (C/EBP)
homologous protein (Chop). Interestingly, autophagy was also enhanced by
aldosterone/MR. Pharmacological inhibition of autophagy resulted in increased
apoptosis. Inhibition of ER stress significantly reduced aldosterone/MR-induced
autophagy. In addition, the activation of ER stress increased the formation of
autophagy, which protected podocytes from apoptosis. Moreover, we observed that
the addition of ROS scavenger, N-acetyl cystein (NAC), blocked both ER stress and
autophagy by aldosterone/MR. Collectively, these results suggest that oxidant
stress-mediated aldosterone/MR-induced podocyte injury via activating ER stress,
which then triggers both Chop-dependent apoptosis and autophagy to cope with the
injury. These findings may guide us to therapeutic strategies for glomerular
diseases.
PMID- 26414310
TI - Coming Together to Move Apart: Family Therapy for Enhancing Adolescent
Development.
AB - An important goal of adolescent development is emotional separation from the
family of origin. Differing views on how to accomplish this task exist, and these
are reflected in the choice of treatment modality. It has been common practice in
the treatment of adolescents for work with parents to be done separately from the
adolescent. Since social, cultural, and economic factors have an impact on
development, as society changes it is important to think creatively about
effective ways to accomplish the process of becoming a functioning adult. It is
in this context that authors have focused recently on the need for young adults
to have a positive connection with their parents. This paper will address the
role of involvement of family in the psychotherapy of adolescents either by
inviting them to participate in some of the individual sessions or through
conjoint family therapy to facilitate forward development. Clinical illustrations
will demonstrate the issues of an adolescent with unresolved early traumatic
separation, an adolescent who is fulfilling parental needs, an adolescent with
too much power in the family, the importance of beginning treatment after
assessing where everyone is emotionally, and the problem of premature
disconnection by parents.
PMID- 26414311
TI - Specific Techniques Vs. Common Factors? Psychotherapy Integration and its Role in
Ethical Practice.
AB - Important change in competent practice in psychological therapy is increasingly
being influenced by evidence-based practice. This paper explores major issues
related to the evidence-based literature with regard to specific techniques and
common factors. Increasing evidence that support common factors provides validity
for the psychotherapy integration movement. This movement is explored in relation
to the three waves of behavior therapy that indicate an increasing integration of
a wide range of therapies. The discussion concludes with implications for
therapists who wish to adopt an ethical and evidence-based approach.
PMID- 26414312
TI - Perfectionism and Personality Disorders as Predictors of Symptoms and
Interpersonal Problems.
AB - Maladaptive perfectionism is a common factor in many disorders and is correlated
with some personality dysfunctions. Less clear is how dimensions, such as concern
over mistakes, doubts about actions, and parental criticism, are linked to
overall suffering. Additionally, correlations between perfectionism and
personality disorders are poorly explored in clinical samples. In this study we
compared a treatment seeking individuals (n=93) and a community sample (n=100) on
dimensions of maladaptive perfectionism, personality disorders, symptoms, and
interpersonal problems. Results in both samples revealed maladaptive
perfectionism was strongly associated with general suffering, interpersonal
problems, and a broad range of personality disordered traits. Excessive concern
over one's errors, and to some extent doubts about actions, predicted unique
additional variance beyond the presence of personality pathology in explaining
symptoms and interpersonal problems.
PMID- 26414313
TI - My Patient, My Stalker Empathy as a Dual-Edged Sword: A Cautionary Tale.
AB - Success in psychotherapy is correlated with the "fit" between patient and
therapist, a factor related to attachment. For psychotherapists of any
orientation, empathy and building the bond of attachment is our stock-in-trade.
When empathy builds the bond of attachment with someone starved for connection, a
therapist may inadvertently set him- or herself up to become a victim of a
stalker. Because individuals who stalk others suffer from severe attachment
disorders, their hunger for attachment motivates them to shadow psychotherapists,
which makes being stalked a very real occupational hazard for psychotherapists.
This was a painful discovery for me. I was stalked for 11 months, leaving me with
post-traumatic stress disorder. After recovering, I deconstructed the experience
to understand how and why it happened, and discovered that it was my empathy and
compassion that contributed to and maintained the stalking. What I learned from
the forensic literature provided the knowledge and confidence needed to end the
stalking. In this paper recommendations are made about how to prevent stalking
and to halt it if it does happens.
PMID- 26414314
TI - Validity of (Ultra-)Short Recordings for Heart Rate Variability Measurements.
AB - OBJECTIVES: In order to investigate the applicability of routine 10s
electrocardiogram (ECG) recordings for time-domain heart rate variability (HRV)
calculation we explored to what extent these (ultra-)short recordings capture the
"actual" HRV. METHODS: The standard deviation of normal-to-normal intervals
(SDNN) and the root mean square of successive differences (RMSSD) were measured
in 3,387 adults. SDNN and RMSSD were assessed from (ultra)short recordings of
10s(3x), 30s, and 120s and compared to 240s-300s (gold standard) measurements.
Pearson's correlation coefficients (r), Bland-Altman 95% limits of agreement and
Cohen's d statistics were used as agreement analysis techniques. RESULTS:
Agreement between the separate 10s recordings and the 240s-300s recording was
already substantial (r = 0.758-0.764/Bias = 0.398-0.416/d = 0.855-0.894 for SDNN;
r = 0.853-0.862/Bias = 0.079-0.096/d = 0.150-0.171 for RMSSD), and improved
further when three 10s periods were averaged (r = 0.863/Bias = 0.406/d = 0.874
for SDNN; r = 0.941/Bias = 0.088/d = 0.167 for RMSSD). Agreement increased with
recording length and reached near perfect agreement at 120s (r = 0.956/Bias =
0.064/d = 0.137 for SDNN; r = 0.986/Bias = 0.014/d = 0.027 for RMSSD). For all
recording lengths and agreement measures, RMSSD outperformed SDNN. CONCLUSIONS:
Our results confirm that it is unnecessary to use recordings longer than 120s to
obtain accurate measures of RMSSD and SDNN in the time domain. Even a single 10s
(standard ECG) recording yields a valid RMSSD measurement, although an average
over multiple 10s ECGs is preferable. For SDNN we would recommend either 30s or
multiple 10s ECGs. Future research projects using time-domain HRV parameters,
e.g. genetic epidemiological studies, could calculate HRV from (ultra-)short ECGs
enabling such projects to be performed at a large scale.
PMID- 26414316
TI - Remediation technologies for oil-contaminated sediments.
AB - Oil-contaminated sediments pose serious environmental hazards for both aquatic
and terrestrial ecosystems. Innovative and environmentally compatible
technologies are urgently required to remove oil-contaminated sediments. In this
paper, various physical, chemical and biological technologies are investigated
for the remediation of oil-contaminated sediments such as flotation and washing,
coal agglomeration, thermal desorption, ultrasonic desorption, bioremediation,
chemical oxidation and extraction using ionic liquids. The basic principles of
these technologies as well as their advantages and disadvantages for practical
application have been discussed. A combination of two or more technologies is
expected to provide an innovative solution that is economical, eco-friendly and
adaptable.
PMID- 26414315
TI - Cerebral Blood Flow Alterations in Acute Sport-Related Concussion.
AB - Sport-related concussion (SRC) is a major health problem, affecting millions of
athletes each year. While the clinical effects of SRC (e.g., symptoms and
functional impairments) typically resolve within several days, increasing
evidence suggests persistent neurophysiological abnormalities beyond the point of
clinical recovery after injury. This study aimed to evaluate cerebral blood flow
(CBF) changes in acute SRC, as measured using advanced arterial spin labeling
(ASL) magnetic resonance imaging (MRI). We compared CBF maps assessed in 18
concussed football players (age, 17.8 +/- 1.5 years) obtained within 24 h and at
8 days after injury with a control group of 19 matched non-concussed football
players. While the control group did not show any changes in CBF between the two
time-points, concussed athletes demonstrated a significant decrease in CBF at 8
days relative to within 24 h. Scores on the clinical symptom (Sport Concussion
Assessment Tool 3, SCAT3) and cognitive measures (Standardized Assessment of
Concussion [SAC]) demonstrated significant impairment (vs. pre-season baseline
levels) at 24 h (SCAT, p < 0.0001; SAC, p < 0.01) but returned to baseline levels
at 8 days. Two additional computerized neurocognitive tests, the Automated
Neuropsychological Assessment Metrics and Immediate Post-Concussion and Cognitive
Testing, showed a similar pattern of changes. These data support the hypothesis
that physiological changes persist beyond the point of clinical recovery after
SRC. Our results also indicate that advanced ASL MRI methods might be useful for
detecting and tracking the longitudinal course of underlying neurophysiological
recovery from concussion.
PMID- 26414318
TI - Heart Rate and VO2 Concordance in Continuous-Flow Left Ventricular Assist
Devices.
AB - The American College of Sports Medicine currently recommends the HR reserve (HRR)
method to guide exercise in individuals who have heart failure with reduced
ejection fraction. This recommendation is based on the known association between
%HRR and percentage of VO2 reserve (%VO2R) in this population. However, to our
knowledge, no studies exist regarding this relation in individuals with a left
ventricular assist device (LVAD). PURPOSE: This article aimed to describe the
relation between VO2 and surrogate markers of exercise intensity among patients
with LVAD. METHODS: Patients with continuous-flow LVAD (n = 24, seven females)
completed a symptom-limited graded exercise test on a treadmill. HR and VO2 were
measured continuously and averaged every 20 s. Regression equations were
determined using a generalized estimating equation to predict %VO2R from %HRR,
Borg RPE, and LVAD flow, overall and stratified by presence of pacing. RESULTS:
Although the association between %HRR and %VO2R was good (R = 0.75), the slope
and y-intercept for %HRR versus %VO2R was different from the line of identity (P
= 0.002). However, when paced subjects were excluded (n = 8) from the analysis,
there was no significant difference between the slope and y-intercept (= 0.036 +
0.937 * %HRR; SEE, 2%; P = 0.052). RPE showed a strong association with %VO2R (R
= 0.84), whereas LVAD flow showed a weak (albeit statistically significant)
association (R = 0.05). Both had slopes and y-intercepts that were different from
the line of identity (P < 0.05). CONCLUSIONS: In patients with LVAD who are not
paced during exercise, the use of %HRR is a good predictor of %VO2R. However, for
patients in this population who are also paced during exercise, RPE is a suitable
surrogate measure of exercise intensity.
PMID- 26414317
TI - Influence of the Metaboreflex on Pulmonary Vascular Capacitance in Heart Failure.
AB - PURPOSE: An impaired metaboreflex is associated with abnormal ventilatory and
peripheral vascular function in heart failure (HF), whereas its influence on
cardiac function or pulmonary vascular pressure remains unclear. We aimed to
assess whether metabolite-sensitive neural feedback (metaboreflex) from locomotor
muscles via postexercise regional circulatory occlusion (RCO) attenuates
pulmonary vascular capacitance (GXCAP) and/or circulatory power (CircP) in
patients with HF. METHODS: Eleven patients with HF (NYHA class, I/II; ages, 51 +/
15 yr; ejection fraction, 32% +/- 9%) and 11 age- and gender-matched controls
(ages, 43 +/- 9 yr) completed three cycling sessions (4 min, 60% peak oxygen
uptake (VO2)). Session 1 was a control trial including normal recovery (NR).
Session 2 or 3 included bilateral upper thigh pressure tourniquets inflated
suprasystolic at end of exercise (RCO) for 2-min recovery with or without
inspired CO2 (RCO + CO2) (randomized). Mean arterial pressure, HR, and VO2 were
continuously measured. Estimates of central hemodynamics; CircP = (VO2 * mean
arterial pressure)/weight; oxygen pulse index (O2pulseI = (VO2/HR)/body surface
area); and GXCAP = O2pulseI * end-tidal partial pressure CO2 were calculated.
RESULTS: At rest and end of exercise, CircP and GXCAP were lower in HF versus
those in controls (P < 0.05), with no differences between transients (P > 0.05).
At 2-min recovery, GXCAP was lower during RCO versus that during NR in both
groups (72 +/- 23 vs 98 +/- 20 and 73 +/- 34 vs 114 +/- 35 mL.beat.mm Hg.m,
respectively; P < 0.05), whereas CircP did not differ between transients (P >
0.05). Differences (% and Delta) between baseline and 2-min recovery among
transients suggest that metaboreflex attenuates GXCAP in HF. Differences (% and
Delta) between baseline and 2-min recovery among transients suggest that
metaboreflex may attenuate CircP in controls. CONCLUSIONS: The present
observations suggest that locomotor muscle metaboreflex activation may influence
CircP in controls but not in HF. However, metaboreflex activation may evoke
decreases in GXCAP (increased pulmonary vascular pressures) in HF and controls.
PMID- 26414319
TI - Cardiac Kinetophagy Coincides with Activation of Anabolic Signaling.
AB - PURPOSE: Growing evidence has shown that endurance exercise is a strong inducer
of autophagy in various tissues. Thus, we define here endurance exercise-induced
autophagy as "kinetophagy" derived from the Greek terms "kineto" (movement),
"auto" (self), and "phagy" (eating). Currently, the exact cellular mechanisms
responsible for kinetophagy remain unclear; hence, we examined kinetophagy
signaling transduction pathways occurring during acute endurance exercise (AEE).
METHODS: C57BL/6 mice were randomly assigned to either AEE (n = 7) or control
sedentary group (CON, n = 7). After 5 d of treadmill running acclimation, mice
performed 60 min of a single bout of treadmill running at 12 m . min(-1) on a 0%
grade. Hearts were excised immediately 1 h after exercise and homogenized for
Western blot analyses. RESULTS: Our data showed that AEE promoted kinetophagy
flux (an increase in LC3-II to LC3-I ratio and LC3-II levels and a reduction in
p62 levels) with Beclin-1 levels suppressed but Atg7 levels elevated compared
with those in the sedentary group. We also observed that AEE increased lysosome
associated membrane protein and cathepsin L, linked to the termination process of
autophagy, and that AEE augmented potent autophagy inducers (i.e., adenosine
monophosphate kinase phosphorylation, BNIP3, and HSP70). Moreover, we found that
exercise-mediated BNIP3 upregulation is associated with hypoxia-inducing factor
1alpha rather than FoxO3a. Intriguingly, we found for the first time that
kinetophagy parallels with anabolic signaling activation (Akt and mammalian
target of rapamycin). CONCLUSIONS: Our findings provide evidence that AEE results
in kinetophagy without a time-associated elevation in Beclin-1 but with the
presence of Akt-mTOR activation and that AEE-induced activation of anabolic
signaling is not associated with kinetophagy promotion.
PMID- 26414321
TI - Directional Energy Transfer in Mixed-Metallic Copper(I)-Silver(I) Coordination
Polymers with Strong Luminescence.
AB - Strongly luminescent mixed-metallic copper(I)-silver(I) coordination polymers
with various Cu/Ag ratio were prepared by utilizing the isomorphous relationship
of the luminescent parent homometallic coordination polymers (Phi(em) = 0.65 and
0.72 for the solid Cu and Ag polymers, respectively, at room temperature). The
mixed-metallic polymer with the mole fraction of copper even as low as 0.005
exhibits a strong emission (Phi(em) = 0.75) from only the copper sites as the
result of the efficient energy migration from the silver to the copper sites. The
migration rates between the two sites were evaluated from the dependence of
emission decays upon the mole fraction of copper.
PMID- 26414320
TI - PeakForce Tapping resolves individual microvilli on living cells.
AB - Microvilli are a common structure found on epithelial cells that increase the
apical surface thus enhancing the transmembrane transport capacity and also serve
as one of the cell's mechanosensors. These structures are composed of
microfilaments and cytoplasm, covered by plasma membrane. Epithelial cell
function is usually coupled to the density of microvilli and its individual size
illustrated by diseases, in which microvilli degradation causes malabsorption and
diarrhea. Atomic force microscopy (AFM) has been widely used to study the
topography and morphology of living cells. Visualizing soft and flexible
structures such as microvilli on the apical surface of a live cell has been very
challenging because the native microvilli structures are displaced and deformed
by the interaction with the probe. PeakForce Tapping(r) is an AFM imaging mode,
which allows reducing tip-sample interactions in time (microseconds) and
controlling force in the low pico-Newton range. Data acquisition of this mode was
optimized by using a newly developed PeakForce QNM-Live Cell probe, having a
short cantilever with a 17-um-long tip that minimizes hydrodynamic effects
between the cantilever and the sample surface. In this paper, we have
demonstrated for the first time the visualization of the microvilli on living
kidney cells with AFM using PeakForce Tapping. The structures observed display a
force dependence representing either the whole microvilli or just the tips of the
microvilli layer. Together, PeakForce Tapping allows force control in the low
pico-Newton range and enables the visualization of very soft and flexible
structures on living cells under physiological conditions.
PMID- 26414322
TI - The Prevalence and Long-Term Outcomes of Extreme Right versus Extreme Left
Ventricular Hypertrophic Cardiomyopathy.
AB - OBJECTIVES: Extreme left ventricular hypertrophy (LVH) is a known risk factor for
sudden cardiac death in hypertrophic cardiomyopathy (HCM). Extreme right
ventricular hypertrophy (RVH) is rare, and whether it is linked to a poor outcome
is unknown. This study was designed to investigate differences between HCM
patients with extreme RVH and those with extreme LVH. METHODS: Among 2,413 HCM
patients, 31 with extreme RVH (maximum right ventricular wall thickness >= 10 mm)
and 194 with extreme LVH (maximum left ventricular wall thickness >= 30 mm) were
investigated. The main clinical features and natural history were compared
between the 2 groups. RESULTS: The prevalence of extreme RVH and extreme LVH was
1.3 and 8.0%, respectively. Patients with extreme RVH tended to be younger and
female (p < 0.01). Cardiovascular-related mortality and morbidity within 10 years
were significantly greater in the extreme RVH group (p < 0.05). Multivariate
analysis demonstrated 3 independent predictors for cardiovascular mortality -
extreme RVH, left ventricular end-diastolic dimension >= 50 mm, and age <= 18
years at baseline - and 2 for morbidity - extreme RVH and presyncope.
CONCLUSIONS: Compared with extreme LVH, extreme RVH was quite uncommon in HCM and
had a worse prognosis. A right ventricle examination should be performed in
routine HCM evaluation.
PMID- 26414323
TI - A Molecular Phylogeny of the Lichen Genus Lecidella Focusing on Species from
Mainland China.
AB - The phylogeny of Lecidella species is studied, based on a 7-locus data set using
ML and Bayesian analyses. Phylogenetic relationships among 43 individuals
representing 11 Lecidella species, mainly from mainland China, were included in
the analyses and phenotypical characters studied and mapped onto the phylogeny.
The Lecidella species fall into three major clades, which are proposed here as
three informal groups-Lecidella stigmatea group, L. elaeochroma group and L.
enteroleucella group, each of them strongly supported. Our phylogenetic analyses
support traditional species delimitation based on morphological and chemical
traits in most but not all cases. Individuals considered as belonging to the same
species based on phenotypic characters were found to be paraphyletic, indicating
that cryptic species might be hidden under these names (e.g. L. carpathica and L.
effugiens). Potentially undescribed species were found within the phenotypically
circumscribed species L. elaeochroma and L. stigmatea. Additional sampling across
a broader taxonomic and geographic scale will be crucial to fully resolving the
taxonomy in this cosmopolitan genus.
PMID- 26414324
TI - HIV-Specific Antibody Responses in HIV-Infected Patients: From a Monoclonal to a
Polyclonal View.
AB - HIV infections represent a major global health threat, affecting more than 35
million individuals worldwide. High infection rates and problems associated with
lifelong antiretroviral treatment emphasize the need for the development of
prophylactic and therapeutic immune intervention strategies. It is conceivable
that insights for the design of new immunogens capable of eliciting protective
immune responses may come from the analysis of HIV-specific antibody responses in
infected patients. Using sophisticated technologies, several monoclonal
neutralizing antibodies were isolated from HIV-infected individuals. However, the
majority of polyclonal antibody responses found in infected patients are
nonneutralizing. Comprehensive analyses of the molecular targets of HIV-specific
antibody responses identified that during natural infection antibodies are mainly
misdirected towards gp120 epitopes outside of the CD4-binding site and against
regions and proteins that are not exposed on the surface of the virus. We
therefore argue that vaccines aiming to induce protective responses should
include engineered immunogens, which are capable of focusing the immune response
towards protective epitopes.
PMID- 26414325
TI - Pancreatic tuberculosis.
AB - Pancreatic tuberculosis is very rare, but recently, there has been a spurt in the
number of reports on pancreatic involvement by tuberculosis. It closely mimics
pancreatic cancer, and before the advent of better imaging modalities it was
often detected as a histological surprise in patients resected for a presumed
pancreatic malignancy. The usual presentation involves abdominal pain, loss of
appetite and weight, jaundice which can be associated with cholestasis, fever and
night sweats, palpable abdominal lump, and peripheral lymphadenopathy. Computed
tomography (CT) of the abdomen is an important tool for evaluation of patients
with pancreatic tuberculosis. This CT imaging yields valuable information about
the size and nature of tubercular lesions along with the presence of ascites and
lymphadenopathy. However, there are no distinctive features on CT that
distinguish it from pancreatic carcinoma. Endoscopic ultrasound provides high
resolution images of the pancreatic lesions as well as an opportunity to sample
these lesions for cytological confirmation. The presence of granulomas is the
most common finding on histological/cytological examination with the presence of
acid fast bacilli being observed only in minority of patients. As there are no
randomized or comparative studies on treatment of pancreatic tuberculosis it is
usually treated like other forms of tuberculosis. Excellent cure rates are
reported with standard anti tubercular therapy given for 6-12 months.
PMID- 26414327
TI - Long-term attraction and toxic effects of tephritid insecticide-bait mixtures by
applying Torricelli's barometer principle in a trapping device.
AB - BACKGROUND: The field activity of the mixtures of liquid baits and insecticides
used in the control of tephritid pests is normally short, both when they are
sprayed or when used in trapping or in attract-and-kill devices. A new lure-and
kill device based on Torricelli's barometer principle was tested as a long
lasting dispenser for two liquid hydrolysed protein baits mixed with insecticide,
GF-120 and Captor 300 + malathion, against Anastrepha ludens (Loew) flies of
laboratory origin. The dispensers were kept under field conditions for 42 days.
Laboratory bioassays for insecticide properties and field cage studies for
attraction capacity were carried out on a weekly basis after 22 and 42 days of
weathering respectively. RESULTS: Our results demonstrated that both mixtures of
insecticides and phagostimulant baits killed up to 80% of the tested flies when
they were 42 days old. The attraction capacity of both weathering-exposed
mixtures was even higher than fresh insecticidal-bait mixtures after the same
period. CONCLUSION: The device is efficient when used with the liquid baits
currently employed in the control of tephritid flies. It also offers a high
potential for combining visual stimuli, such as shape and colour, and for
improving trapping and bait station designs. Incorporating this new device in
trapping and attract-and-kill methods could help to reduce the frequency of
servicing of the traps and bait stations and lower their costs. (c) 2015 Society
of Chemical Industry.
PMID- 26414328
TI - Randomly and Non-Randomly Missing Renal Function Data in the Strong Heart Study:
A Comparison of Imputation Methods.
AB - Kidney and cardiovascular disease are widespread among populations with high
prevalence of diabetes, such as American Indians participating in the Strong
Heart Study (SHS). Studying these conditions simultaneously in longitudinal
studies is challenging, because the morbidity and mortality associated with these
diseases result in missing data, and these data are likely not missing at random.
When such data are merely excluded, study findings may be compromised. In this
article, a subset of 2264 participants with complete renal function data from
Strong Heart Exams 1 (1989-1991), 2 (1993-1995), and 3 (1998-1999) was used to
examine the performance of five methods used to impute missing data: listwise
deletion, mean of serial measures, adjacent value, multiple imputation, and
pattern-mixture. Three missing at random models and one non-missing at random
model were used to compare the performance of the imputation techniques on
randomly and non-randomly missing data. The pattern-mixture method was found to
perform best for imputing renal function data that were not missing at random.
Determining whether data are missing at random or not can help in choosing the
imputation method that will provide the most accurate results.
PMID- 26414334
TI - Representing scale: What should be special about the heritage of mass science?
AB - This symposium marks the achievement of a transformation in the history of
science. Whereas in the 1960s, the study of modern developments was marginal to
the field, it has now become a key part of the discipline's central concerns. The
contrast between this conference and a 1960 symposium is illuminating. The paper
reflects on the tensions over the future direction of the discipline expressed at
the 1974 semi-centenary conference of the History of Science Society. Today,
genomics with its vast demand for resources and its challenges to traditional
boundaries is not untypical of a wide range of scientific activities. Its study
can serve as a pioneering case study interesting for itself and important for a
wider understanding of science. Papers at this meeting show the implications for
the understanding of methods, appropriate targets of study, the interpretation of
images and the preservation of archives.
PMID- 26414329
TI - Alterations in Daytime and Nighttime Activity in Piglets after Focal and Diffuse
Brain Injury.
AB - We have developed and implemented a noninvasive, objective neurofunctional
assessment for evaluating the sustained effects of traumatic brain injury (TBI)
in piglets with both diffuse and focal injury types. Derived from commercial
actigraphy methods in humans, this assessment continuously monitors the day/night
activity of piglets using close-fitting jackets equipped with tri-axial
accelerometers to monitor movements of the thorax. Acceleration metrics were
correlated (N = 7 naive piglets) with video images to define values associated
with a range of activities, from recumbancy (rest) to running. Both focal (N = 8)
and diffuse brain injury (N = 9) produced alterations in activity that were
significant 4 days post-TBI. Compared to shams (N = 6) who acclimated to the
animal facility 4 days after an anesthesia experience by blurring the distinction
between day and night activity, post-TBI time-matched animals had larger
fractions of inactive periods during the daytime than nighttime, and larger
fractions of active time in the night were spent in high activity (e.g., constant
walking, intermittent running) than during the day. These persistent disturbances
in rest and activity are similar to those observed in human adults and children
post-TBI, establishing actigraphy as a translational metric, used in both humans
and large animals, for assessment of injury severity, progressions, and
intervention.
PMID- 26414335
TI - Infant outcomes following midtrimester emergency cerclage in the presence of
fully dilated cervix and prolapsing amniotic membranes into the vagina.
AB - OBJECTIVE: To investigate the morbidity of infants, whose delivery was prolonged
by an emergency cervical cerclage (EC). METHODS: Ante- and postnatal data on
subsequent EC procedures performed between 14 and 28 weeks of gestation for
advanced cervical dilatation with prolapsing of amniotic membranes at a single
institution within a 5-year-period were retrieved. RESULTS: We identified 21
fetuses from 18 pregnancies. Median gestational age [interquartile range, IQR] at
EC and prolongation of pregnancy was 21.5 [15-26] weeks and 49.3 [24-92] days,
respectively. There were 4 (19%) stillbirths, 3 (14%) neonatal deaths, and 1 (5%)
infant death. Ten infants (59% of livebirths) were admitted to neonatal intensive
care unit and hospitalized for a median period of 11 [6-66] d. Of the surviving
fetuses (14/21, 66.7%), 9 (42.8%) were intact, whereas 3 (17.6% of livebirths)
had cerebral palsy (CP), 1 was diagnosed with hypothyroidism, and another had
growth failure at 12 months of follow-up. CONCLUSION: EC seems to be beneficial
only in a subset of pregnancies presenting with full cervical dilatation
accompanied by prolapsing amniotic membranes into the vagina, and there is a
requirement for more objective selection criteria. Neonatal morbidity, especially
neurodevelopmental disability should be discussed thoroughly prior to this
procedure.
PMID- 26414336
TI - Recurrence of hepatocellular carcinoma after liver transplantation: an update.
AB - Liver transplantation is the only curative alternative for selected patients with
hepatocellular carcinoma (HCC) who are not eligible for resection and/or with
decompensated cirrhosis. According to Milan criteria the 5-year survival rate is
70-85%, with a recurrence-free survival of 75%. However, HCC recurrence rate
after liver transplantation remains a significant problem in the clinical
practice. The prognosis in patients with HCC recurrence is poor. The treatment of
choice for HCC recurrence is surgery, but it seems that a systemic treatment
based on combination of an mTOR inhibitor with sorafenib can be used. Data on
safety and efficacy are limited, clinical monitoring is necessary. The aim of
this review is to underline the main concerns, pitfalls and warnings for these
patients.
PMID- 26414337
TI - Varenicline for treatment of alcohol dependence: a randomized, placebo-controlled
trial.
AB - BACKGROUND: Alcohol dependence is a devastating illness affecting a large
population, and new pharmacological treatments with good efficacy are greatly
needed. One potential candidate is varenicline, a smoking cessation agent with
partial agonist action at alpha4 beta2 nicotinic acetylcholine receptors.
METHODS: A total of 160 subjects, 30 to 70 years of age, fulfilling DSM-IV
criteria for alcohol dependence without any serious physical or mental disorders,
were recruited through advertisement at 3 university clinics in Sweden during
March 2009 to January 2011. After a 2-week placebo run-in period, subjects
received 2 mg varenicline daily (titrated from 0.5 mg during first week) or
placebo for 12 weeks in a double-blind manner. RESULTS: The primary outcome was
the proportion of heavy drinking days, measured by self-reported alcohol
consumption. Primary and secondary outcomes were calculated as a mean over the 10
week steady-state active treatment period. In the primary outcome analysis, no
effect of varenicline over placebo was found (p = 0.73 for the intention to treat
[ITT] and 0.92 for per protocol [PP]). Secondary outcome analysis found a
significant reduction of specific alcohol marker phosphatidylethanol (PEth) in
the blood in the varenicline group compared to placebo (p = 0.02 ITT). Craving (p
= 0.048 PP) and Alcohol Use Disorders Identification Test (AUDIT) scores (p =
0.015 ITT) were also reduced in the active treatment group. PEth more strongly
correlated with self-reported alcohol consumption than carbohydrate-deficient
ttransferrin and gamma-glutamyl transferase, and correlation coefficients were
higher in the varenicline group than in the placebo group for all markers.
CONCLUSIONS: Although the results of the main outcome of this study did not
support an effect of varenicline in alcohol-dependent individuals, the secondary
analyses of PEth, craving and AUDIT score support an effect of varenicline on
alcohol consumption. The disclosure of a treatment effect and the lack of a clear
placebo effect when using PEth as outcome variable, together with a nonsymmetric
bias associated with self-reported data, strongly argue for using the specific
biomarker PEth in studies of treatments of alcohol dependence.
PMID- 26414339
TI - In Situ, Simultaneous Irradiation and Monitoring of a Photocatalyzed Organic
Oxidation Reaction in a TiO2-Coated NMR Tube.
AB - The semiconductor photocatalyzed (SPC) oxidation of toluene is performed inside
an NMR spectrometer and the reaction is monitored simultaneously in situ, using a
fiber optic probe/diffuser to provide the UV light to activate the titania
photocatalyst coating on the inside of the NMR tube. Such a system has great
potential for the simple rapid screening of a wide range of SPC mediated organic
reactions.
PMID- 26414338
TI - Clotting factor product administration and same-day occurrence of thrombotic
events, as recorded in a large healthcare database during 2008-2013.
AB - BACKGROUND: Thrombotic events (TEs) are serious adverse events that can occur
following administration of clotting factors (CFs). OBJECTIVES: To evaluate
occurrence of same-day TEs for different CF products and potential risk factors.
METHODS: A retrospective cohort study of individuals exposed to CF products
during 2008-2013 was conducted using a large commercial insurance database. CF
products were identified by procedure codes, and TEs were ascertained via
diagnosis codes. Crude same-day TE rates (per 1000 persons exposed) were
estimated overall and by congenital factor deficiency (CFD) status, CF products,
age and gender. Multivariable logistic regression analyses were used to control
for confounding. Laboratory analysis was used to compare the procoagulant
activities of FIX products. RESULTS: Of 3801 individuals exposed to CFs, 117
(30.8 per 1000) had same-day TEs recorded. The crude same-day TE rate was higher
for CF users without CFD, 70.2 (102 of 1452), as compared with those with CFD,
6.4 (15 of 2349) (RR, 11.0; 95% CI, 6.4-18.9). For individuals without CFD, a
significantly increased same-day TE risk was identified for factor IX complex
(OR, 6.92; 95% CI, 3.11-15.40), factor VIIa (OR, 9.42; 95% CI, 4.99-17.78) and
other products when compared with fibrin sealant. An increased risk of a TE was
found with older age (>= 45 years), history of TEs and underlying health
conditions. The laboratory identified elevated procoagulant activity in
Profilnine((r)) and Benefix((r)) . CONCLUSIONS: The study shows an increased same
day TE risk for CF users without CFD and suggests substantial off-label CF use.
The study findings also show elevated same-day TE rates for different CF products
and suggest the importance of product properties and patient factors.
PMID- 26414340
TI - Simultaneously modulated accelerated radiation therapy reduces severe oesophageal
toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung
cancer.
AB - OBJECTIVE: The aim of this study was to evaluate the potential of simultaneously
modulated accelerated radiation therapy (SMART) to reduce the incidence of severe
acute oesophagitis in the treatment of unresectable locally advanced non-small
cell lung cancer (LANSCLC). METHODS: 21 patients were treated with SMART and
concomitant platinum-based chemotherapy. The prescribed doses were limited to 54
Gy at 1.8 Gy per day to the zones of presumed microscopic extent while
simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic
disease. The whole treatment was delivered over 30 fractions and 6 weeks.
Dosimetric parameters of SMART and the standard technique of irradiation
[intensity-modulated radiation therapy (IMRT)] were compared. Acute toxicity was
prospectively recorded. RESULTS: The highest grade of oesophagitis was 62% (13
patients) grade 1, 33% (7 patients) grade 2 and 5% (1 patient) grade 3. Three
(14%) patients experienced acute grade 2 pneumonitis. There was no grade 4
oesophageal or pulmonary toxicity. Doses to the organs at risk were significantly
reduced in SMART compared with IMRT [oesophagus: V50Gy, 28.5 Gy vs 39.9 Gy (p =
0.003); V60Gy, 7.1 Gy vs 30.7 Gy (p = 0.003); lung: V20Gy, 27.4 Gy vs 30.1 Gy (p
= 0,002); heart: V40Gy, 7.3 Gy vs 10.7 Gy (p = 0.006); spine: Dmax, 42.4 Gy vs
46.4 Gy (p = 0.003)]. With a median follow-up of 18 months (6-33 months), the 1
year local control rate was 70% and the disease-free survival rate was 47%.
CONCLUSION: SMART reduces the incidence of severe oesophagitis and improves the
whole dosimetric predictors of toxicity for the lung, heart and spine. ADVANCES
IN KNOWLEDGE: Our study shows that SMART optimizes the therapeutic ratio in the
treatment of LANSCLC, opening a window for dose intensification.
PMID- 26414341
TI - Safety and tolerability of lacosamide as adjunctive therapy for adults with
partial-onset seizures: Analysis of data pooled from three randomized, double
blind, placebo-controlled clinical trials.
AB - OBJECTIVE: The objective of this study was to describe a priori protocol-defined
analyses to evaluate the safety and tolerability of adjunctive oral lacosamide
(200-600 mg/day) in adults (ages 16-70 years) with partial-onset seizures (POS)
using data pooled from three similarly designed randomized, double-blind, placebo
controlled trials (SP667, SP754 [NCT00136019], SP755 [NCT00220415]). METHODS:
Patients with POS (>=2 years' duration, >=2 previous antiepileptic drugs [AEDs])
uncontrolled by a stable dosing regimen of 1-3 concomitant AEDs were randomized
to treatment with lacosamide at doses of 200 mg/day, 400 mg/day, or 600 mg/day,
or placebo. Studies comprised a 4- to 6-week titration phase to target dose
followed by a 12-week maintenance phase. Safety outcomes included treatment
emergent adverse events (TEAEs) of particular relevance to patients with POS,
overall TEAEs, and discontinuations due to TEAEs. Post hoc analyses included
evaluation of TEAEs potentially related to cognition and TEAEs leading to
discontinuation analyzed by concomitant AEDs. RESULTS: One thousand three hundred
eight patients were randomized to and received treatment; 944 to lacosamide and
364 to placebo. Most patients (84.4%) were taking 2 or 3 concomitant AEDs. The
most common drug-associated TEAEs (reported by >=5% of patients in any lacosamide
dose group and with an incidence at least twice that reported for placebo during
the treatment phase) were dizziness (30.6% for lacosamide vs 8.2% for placebo),
nausea (11.4% vs 4.4%), and diplopia (10.5% vs 1.9%). Common drug-associated
TEAEs generally appeared to be dose-related, and the incidence of each was lower
during the 12-week maintenance phase than during the titration phase. Most TEAEs
were either mild or moderate in intensity; severe TEAEs were predominantly
observed with lacosamide 600 mg/day. No individual serious TEAE occurred in >=1%
of all lacosamide-treated patients. Treatment-emergent adverse events led to
discontinuation in 8.1%, 17.2%, and 28.6% of the lacosamide 200-, 400-, and 600
mg/day groups, respectively (vs 4.9% of placebo). Few TEAEs were related to rash,
weight loss/gain, changes in clinical chemistry parameters, or psychiatric
disturbances, or were seizure-related. The odds of reporting any potential
cognition-related TEAE vs placebo increased with dose and were similar between
lacosamide doses of 200 and 400mg/day and placebo (odds ratio 1.3, 95% confidence
interval 0.7-2.4). Discontinuations due to TEAEs based on most commonly used AEDs
taken in combination with lacosamide (all doses combined) were carbamazepine
(15.3% [51/334] vs 3.9% [5/129] placebo), lamotrigine (19.2% [56/291] vs 4.3%
[5/117]), and levetiracetam (10.1% [28/278] vs 3.9% [4/103]). CONCLUSIONS: The
safety and tolerability profile of adjunctive lacosamide in this detailed
evaluation was similar to that observed in the individual double-blind trials.
Adjunctive lacosamide was associated with TEAEs related to the nervous system and
gastrointestinal tract, predominantly during titration.
PMID- 26414342
TI - Stigma and quality of life at long-term follow-up after surgery for epilepsy in
Uganda.
AB - Epilepsy is a worldwide health problem with a 10-fold greater prevalence in the
developing world. Commonly, the seizure focus is in the temporal lobe, and
seizures in about 30% of people with epilepsy are intractable to medication. For
these individuals, surgery for intractable temporal lobe epilepsy (iTLE) is more
effective than medication alone and may be the only option for cure. Intractable
temporal lobe epilepsy is associated with elevated morbidity and mortality,
reduced quality of life (QOL), and associated stigma particularly occurring in
the developing world. Individuals with intractable epilepsy who participated in
an earlier Uganda pilot study were selected for the current study based on their
undergoing previous surgery for iTLE or having comparable seizure type who did
not have surgery. At long-term follow-up, 10 who underwent surgery for iTLE in
addition to 9 patients with focal dyscognitive type epilepsy who did not have
surgery were evaluated in the current study. Tests were administered to look at
various outcome parameters: seizure severity, QOL, stigma, and self-esteem.
Stigma and self-esteem were additionally evaluated in the parent/caregiver.
Seventy-percent of surgical resection patients were seizure-free at 8 years
postsurgery. The QOLIE-31 scores were higher in surgical patients. Child/patient
and parent/proxy surveys identified lower stigma in seizure-free patients. The
results suggest that surgery for iTLE is an effective treatment for epilepsy in
the developing world and provides an opportunity to reduce stigma and improve
QOL.
PMID- 26414343
TI - A randomized controlled multimodal behavioral intervention trial for improving
antiepileptic drug adherence.
AB - PURPOSE: Medication nonadherence is one of the most important reasons for
treatment failure in patients with epilepsy. The present study investigated the
effectiveness of a multicomponent intervention to improve adherence to
antiepileptic drug (AED) medication in patients with epilepsy. METHODS: In a
prospective, randomized multicenter trial, three sessions of face-to-face
motivational interviewing (MI) in combination with complementary behavior change
techniques were compared with standard care. Motivational interviewing prompted
change talk and self-motivated statements from the patients, planning their own
medication intake regimen and also identifying and overcoming barriers that may
prevent adherence. Participants were provided with calendars to self-monitor
their medication taking behavior. A family member and the health-care team were
invited to attend the last session of MI in order to improve the collaboration
and communication between patients, their caregiver or family member, and their
health-care provider. At baseline and 6-month follow-up, psychosocial variables
and medical adherence were assessed. RESULTS: In total, 275 participants were
included in the study. Compared with the active control group, patients in the
intervention group reported significantly higher medication adherence, as well as
stronger intention and perceptions of control for taking medication regularly.
The intervention group also reported higher levels of action planning, coping
planning, self-monitoring, and lower medication concerns. CONCLUSIONS: This study
shows that MI can be effective in clinical practice to improve medication
adherence in patients with epilepsy. It also provides evidence that combining
volitional interventions, including action planning, coping planning, and self
monitoring with motivational interviewing can promote the effectiveness of the
medical treatments for epilepsy by improving adherence.
PMID- 26414344
TI - Personalities of patients with nonepileptic psychogenic status.
AB - The purposes of this study were to determine whether personalities of patients
with nonepileptic psychogenic status (NEPS) are different from those of patients
with typical intermittent psychogenic nonepileptic seizures (iPNES) using the
Personality Assessment Inventory (PAI) and to compare their PAI profiles with the
population norms. We hypothesized that patients with NEPS have more
psychopathology compared with patients with iPNES and that, as a group, patients
with PNES (iPNES+NEPS) would have more psychopathology compared with healthy
individuals. We first compared the PAI profiles of patients with iPNES and NEPS
and then the profiles of patients with NEPS, iPNES, and PNES with population
norms in order to assess which PAI specific scales differed between groups in
order to better characterize the psychopathology of PNES. All patients admitted
for diagnostic evaluation to the epilepsy monitoring unit (EMU) were
prospectively approached for participation. All patient/family interviews were
conducted by an epileptologist, and the diagnosis of iPNES or NEPS was confirmed
in all cases through video/EEG and/or family interview. The population norms for
PAI were obtained from the manual. Of the 224 approached patients, 130 completed
the PAI, and included 43 iPNES and 11 with NEPS. There were no significant
differences between the two groups in regard to demographic or PAI profiles.
Comparison with population norms revealed the presence of abnormal personality
profiles on all scales in patients with iPNES, NEPS, or PNES. We conclude that
while the occurrence of NEPS is relatively common in patients with PNES, the
demographic characteristics and personality profiles of patients with NEPS are
not different from those of patients with iPNES. We also confirmed the presence
of significant psychopathology in the group with PNES when compared with
population norms.
PMID- 26414345
TI - Association of knowledge about epilepsy with mood and self-efficacy in Korean
people with epilepsy.
AB - PURPOSE: We determined the level of knowledge about epilepsy in Korean people
with epilepsy (PWE) and evaluated whether this is associated with self-efficacy,
perceived stigma, anxiety, and depressive mood in these patients. METHODS: This
was a cross-sectional multicenter study. A total of 530 PWE participated from 31
secondary or tertiary hospitals in Korea. Knowledge about epilepsy was assessed
using 34 medical items (EKP-M) of the Epilepsy Knowledge Profile-General.
Additional questionnaires included the Epilepsy Self-Efficacy Scale (ESES),
Stigma Scale, and Hospital Anxiety and Depression Scale (HADS). Multiple linear
regression analyses were used. RESULTS: The mean EKP-M score was 22.2 (SD: 4.1).
By univariate analyses, the EKP-M was related to ESES (r=0.220, p<0.001) and HADS
D (r=-0.154, p<0.001) scores but not to the Stigma Scale or HADS-A. By linear
regression analyses, after adjusting for the confounding variables, the higher
EKP-M scores were independently related to both higher ESES (p<0.001) and lower
HADS-D scores (p<0.05). CONCLUSION: Korean PWE have a relatively low level of
knowledge about their condition. Knowledge about epilepsy is associated with a
high level of self-efficacy and less depressive symptoms in affected individuals.
PMID- 26414346
TI - Activating therapy modalities in older individuals with chronic non-specific low
back pain: a systematic review.
AB - BACKGROUND: Although there are many special exercise-based therapy approaches for
the working population suffering chronic low back pain, similar programmes for
older individuals are rare. OBJECTIVES: To summarise all evaluated physical
therapy approaches, and assess the effects on older people with chronic low back
pain. DATA SOURCES: Medline, CINAHL, Cochrane, Embase, PEDro, PsychINFO and
Psyndex. STUDY SELECTION/ELIGIBILITY: Age>=65 years, subacute or chronic non
specific low back pain of >=6weeks' duration, and a physical therapy approach.
STUDY APPRAISAL AND SYNTHESIS METHODS: Study selection, data extraction, and
assessment of methodological quality and clinical relevance were performed
independently by two reviewers. As there were only a few controlled trials and
wide heterogeneity in observation periods and outcome measures, pooling of data
was not feasible. Therefore, the results are presented descriptively. RESULTS: In
total, nine studies were included; six related to mixed physiotherapy modalities,
one related to strength training, and two related to endurance training. Low
quality evidence suggests that physical therapy modalities are associated with a
small-to-moderate reduction in pain and a small improvement in function.
LIMITATIONS: The results must be interpreted with caution due to poor
methodological quality. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: Few studies
have been performed in this highly relevant and growing age group. It is not
possible to recommend one particular modality or programme; as such,
prescriptions should reflect patients' preferences and local conditions. Further
research of higher methodological quality is needed urgently.
PMID- 26414347
TI - The Structure of Plasmodium falciparum Blood-Stage 6-Cys Protein Pf41 Reveals an
Unexpected Intra-Domain Insertion Required for Pf12 Coordination.
AB - Plasmodium falciparum is an apicomplexan parasite and the etiological agent of
severe human malaria. The complex P. falciparum life cycle is supported by a
diverse repertoire of surface proteins including the family of 6-Cys s48/45
antigens. Of these, Pf41 is localized to the surface of the blood-stage merozoite
through its interaction with the glycophosphatidylinositol-anchored Pf12. Our
recent structural characterization of Pf12 revealed two juxtaposed 6-Cys domains
(D1 and D2). Pf41, however, contains an additional segment of 120 residues
predicted to form a large spacer separating its two 6-Cys domains. To gain
insight into the assembly mechanism and overall architecture of the Pf12-Pf41
complex, we first determined the 2.45 A resolution crystal structure of Pf41
using zinc single-wavelength anomalous dispersion. Structural analysis revealed
an unexpected domain organization where the Pf41 6-Cys domains are, in fact,
intimately associated and the additional residues instead map predominately to an
inserted domain-like region (ID) located between two beta-strands in D1. Notably,
the ID is largely proteolyzed in the final structure suggesting inherent
flexibility. To assess the contribution of the ID to complex formation, we
engineered a form of Pf41 where the ID was replaced by a short glycine-serine
linker and showed by isothermal titration calorimetry that binding to Pf12 was
abrogated. Finally, protease protection assays showed that the proteolytic
susceptibility of the ID was significantly reduced in the complex, consistent
with the Pf41 ID directly engaging Pf12. Collectively, these data establish the
architectural organization of Pf41 and define an essential role for the Pf41 ID
in promoting assembly of the Pf12-Pf41 heterodimeric complex.
PMID- 26414349
TI - Abstracts of Award-Winning Posters, 20th Annual Health Sciences Poster
Conference, Faculty of Medicine, Health Sciences Centre, Kuwait University,
Kuwait, May 5-7, 2015.
PMID- 26414348
TI - The Inhibition of Heat Shock Protein 90 Facilitates the Degradation of Poly
Alanine Expanded Poly (A) Binding Protein Nuclear 1 via the Carboxyl Terminus of
Heat Shock Protein 70-Interacting Protein.
AB - BACKGROUND: Since the identification of poly-alanine expanded poly(A) binding
protein nuclear 1 (PABPN1) as the genetic cause of oculopharyngeal muscular
dystrophy (OPMD), considerable progress has been made in our understanding of the
pathogenesis of the disease. However, the molecular mechanisms that regulate the
onset and progression of the disease remain unclear. RESULTS: In this study, we
show that PABPN1 interacts with and is stabilized by heat shock protein 90
(HSP90). Treatment with the HSP90 inhibitor 17-AAG disrupted the interaction of
mutant PABPN1 with HSP90 and reduced the formation of intranuclear inclusions
(INIs). Furthermore, mutant PABPN1 was preferentially degraded in the presence of
17-AAG compared with wild-type PABPN1 in vitro and in vivo. The effect of 17-AAG
was mediated through an increase in the interaction of PABPN1 with the carboxyl
terminus of heat shock protein 70-interacting protein (CHIP). The overexpression
of CHIP suppressed the aggregation of mutant PABPN1 in transfected cells.
CONCLUSIONS: Our results demonstrate that the HSP90 molecular chaperone system
plays a crucial role in the selective elimination of abnormal PABPN1 proteins and
also suggest a potential therapeutic application of the HSP90 inhibitor 17-AAG
for the treatment of OPMD.
PMID- 26414352
TI - Epidermal growth factor receptor tyrosine kinase inhibitors in elderly patients
with non-small cell lung cancer.
AB - Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths
worldwide. At diagnosis, half of the patients are over 70 years of age, and most
present with advanced disease, for which chemotherapy is recommended as first
line treatment. However, the benefit from such therapy is modest and it is at
times poorly tolerated. The discovery of epidermal growth factor receptor
tyrosine kinase inhibitors (EGFR-TKIs) has significantly impacted the treatment
of patients with EGFR mutation-positive advanced NSCLC. These novel agents
demonstrate efficacy and a favorably mild toxicity profile. Despite limited data
in elderly patients, the largest subpopulation in NSCLC, EGFR-TKIs are considered
the standard of care therapy for advanced EGFR-positive disease in the elderly.
In this review, we seek to compile the available data about the EGFR-TKIs use in
elderly patients with advanced NSCLC, with the hope to better understand its role
in this major yet, underrepresented, group of patients.
PMID- 26414351
TI - Subangstrom single-molecule measurements of motor proteins using a nanopore.
AB - Techniques for measuring the motion of single motor proteins, such as FRET and
optical tweezers, are limited to a resolution of ~300 pm. We use ion current
modulation through the protein nanopore MspA to observe translocation of helicase
Hel308 on DNA with up to ~40 pm sensitivity. This approach should be applicable
to any protein that translocates on DNA or RNA, including helicases, polymerases,
recombinases and DNA repair enzymes.
PMID- 26414350
TI - A catalog of the mouse gut metagenome.
AB - We established a catalog of the mouse gut metagenome comprising ~2.6 million
nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure
high microbiome diversity, we used mouse strains of diverse genetic backgrounds,
from different providers, kept in different housing laboratories and fed either a
low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the
cataloged genes are bacterial. We identified 541 metagenomic species and defined
a core set of 26 metagenomic species found in 95% of the mice. The mouse gut
microbiome is functionally similar to its human counterpart, with 95.2% of its
Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common.
However, only 4.0% of the mouse gut microbial genes were shared (95% identity,
90% coverage) with those of the human gut microbiome. This catalog provides a
useful reference for future studies.
PMID- 26414353
TI - Electroencephalographic Monitoring of Brain Wave Activity During Laparoscopic
Surgical Simulation to Measure Surgeon Concentration and Stress: Can the Student
Become the Master?
AB - PURPOSE: To measure gamma and alpha brain wave activity as a measurement of
concentration and stress levels during surgical simulator performance of
laparoscopic tasks to determine if expert surgeons have different brain activity
patterns compared with intermediate and novice surgeons. MATERIALS AND METHODS:
After obtaining Institutional Review Board approval, 1st and 2nd year medical
students, urology residents (PGY2-PGY5), and attending urologists from one
institution were recruited. Participants were stratified by level of experience
and performed laparoscopic tasks on the EDGE laparoscopic simulator. Subjects
were evaluated for concentration and stress levels using the
electroencephalography (EEG) data extracted from the MUSE(TM) headband. The MUSE
software developer kit (SDK) allowed quantification of gamma and alpha waves
during each task. An analysis of variance was used to compare concentration and
stress levels between groups. RESULTS: A total of 19 participants were recruited
for the study and stratified by surgical experience into novice, intermediate,
and expert laparoscopy groups: 6 medical students, 9 urology residents, and 4
attending urologists, respectively. Concentration and stress were quantified by
calculating the area under the curve of the gamma and alpha EEG wave tracings.
Stress was significantly lower in the attending urologists compared with the
residents and medical students during the laparoscopic suturing and trended
toward significance in the peg transfer task (P = 0.0003, P = 0.069).
Concentration was significantly higher in the expert group compared with the less
experienced groups during both the peg and suture tasks (P = 0.036, P = 0.0039).
CONCLUSIONS: EEG brain activity in more experienced surgeons reveals a
significant increase in concentration levels with a decrease in stress during
simulated laparoscopic tasks compared with novices. This information may
correlate with increased proficiency as well as provide objective feedback of
progress along the learning curve with the MUSE SDK.
PMID- 26414354
TI - Link Between Increased Prevalence of Autism Spectrum Disorder Syndromes and
Oxidative Stress, DNA Methylation, and Imprinting: The Impact of the Environment.
PMID- 26414355
TI - An updated review on gastro-esophageal reflux in pediatrics.
AB - Comprehensive guidelines for the diagnosis and management of gastro-esophageal
reflux (GER) and GER disease (GERD) were developed by the European and North
American Societies for Pediatric Gastroenterology, Hepatology and Nutrition. GERD
is reflux associated with troublesome symptoms or complications. The recognition
of GER and GERD is relevant to implement best management practices. A
conservative management is indicated in infants with uncomplicated physiologic
reflux. Children with GERD may benefit from further evaluation and treatment.
Since the publications of the European and North American Societies for Pediatric
Gastroenterology, Hepatology and Nutrition guidelines in 2009, no important
novelties in drug treatment have been reported. Innovations are mainly restricted
to the management of regurgitation in infants. During the last 5 years, pros and
cons of multichannel intraluminal impedance have been highlighted. However,
overall 'not much has changed' in the diagnosis and management of GER and GERD in
infants and children.
PMID- 26414356
TI - Visual Stimuli Evoked Action Potentials Trigger Rapidly Propagating Dendritic
Calcium Transients in the Frog Optic Tectum Layer 6 Neurons.
AB - The superior colliculus in mammals or the optic tectum in amphibians is a major
visual information processing center responsible for generation of orientating
responses such as saccades in monkeys or prey catching avoidance behavior in
frogs. The conserved structure function of the superior colliculus the optic
tectum across distant species such as frogs, birds monkeys permits to draw rather
general conclusions after studying a single species. We chose the frog optic
tectum because we are able to perform whole-cell voltage-clamp recordings
fluorescence imaging of tectal neurons while they respond to a visual stimulus.
In the optic tectum of amphibians most visual information is processed by pear
shaped neurons possessing long dendritic branches, which receive the majority of
synapses originating from the retinal ganglion cells. Since the first step of the
retinal input integration is performed on these dendrites, it is important to
know whether this integration is enhanced by active dendritic properties. We
demonstrate that rapid calcium transients coinciding with the visual stimulus
evoked action potentials in the somatic recordings can be readily detected up to
the fine branches of these dendrites. These transients were blocked by calcium
channel blockers nifedipine CdCl2 indicating that calcium entered dendrites via
voltage-activated L-type calcium channels. The high speed of calcium transient
propagation, >300 MUm in <10 ms, is consistent with the notion that action
potentials, actively propagating along dendrites, open voltage-gated L-type
calcium channels causing rapid calcium concentration transients in the dendrites.
We conclude that such activation by somatic action potentials of the dendritic
voltage gated calcium channels in the close vicinity to the synapses formed by
axons of the retinal ganglion cells may facilitate visual information processing
in the principal neurons of the frog optic tectum.
PMID- 26414359
TI - Eyes wide open: reader and author responsibility in understanding the limits of
peer review.
AB - 'Medical science can only flourish in a free society and dies under totalitarian
repression.' (1) Peer review post-publication is relatively easy to define: when
the world decides the importance of publication. Peer review pre-publication is
what the scientific community frequently means when using the term 'peer review'.
But what it is it? Few will agree on an exact definition; generally speaking, it
refers to an independent, third party scrutiny of a manuscript by scientific
experts (called peers) who advise on its suitability for publication. Peer review
is expensive; although reviewers are unpaid, the cost in time is enormous and it
is slow. There is often little agreement among reviewers about whether an article
should be published and peer review can be a lottery. Often referred to as a
quality assurance process, there are many examples of when peer review failed.
Many will be aware of Woo-Suk Hwang's shocking stem cell research misconduct at
Seoul National University. (2) Science famously published two breakthrough
articles that were found subsequently to be completely fabricated and this
happened in spite of peer review. Science is not unique in making this error.
However, love it or hate it, peer review, for the present time at least, is here
to stay. In this article, Philippa Benson, Managing Editor of Science Advances
(the first open access journal of the American Association for the Advancement of
Science), discusses the merits of peer review. Dr Benson has extensive experience
in the publishing world and was Executive Director of PJB Consulting, a not-for
profit organisation supporting clients on issues related to converting to full
electronic publishing workflows as well as challenges working with international
authors and publishers. Her clients included the Public Library of Science
journals, the American Society for Nutrition and the de Beaumont Foundation. She
recently co-authored a book, What Editors Want: An Author's Guide to Scientific
Journal Publishing (University of Chicago Press), which helps readers understand
and navigate the publishing process in high impact science and technical
journals. Her master's and doctorate degrees are from Carnegie Mellon University.
JYOTI SHAH Commissioning Editor References 1. Eaton KK . Editorial: when is a
peer review journal not a peer review journal? J Nutr Environ Med 1997 ; 7 : 139
144 . 2. van der Heyden MA , van de Ven T , Opthof T . Fraud and misconduct in
science: the stem cell seduction . Neth Heart J 2009 ; 17 : 25 - 29 .
PMID- 26414358
TI - Novel Food Supplement "CP1" Improves Motor Deficit, Cognitive Function, and
Neurodegeneration in Animal Model of Parkinson's Disease.
AB - Based on pivotal roles of oxidative stress, dopaminergic and cholinergic systems
on the pathophysiology of Parkinson's disease (PD), the searching for functional
food for patients attacked with PD from Cyperus rotundus and Zingiber officinale,
the substances possessing antioxidant activity, and the suppression effects on
monoamine oxidase B (MAO-B) and acetylcholinesterase (AChE) have been considered.
In this study, we aimed to determine the effect of the combined extract of C.
rotundus and Z. officinale (CP1) to improve motor and memory deficits,
neurodegeneration, oxidative stress, and functions of both cholinergic and
dopaminergic systems in the animal model of PD induced by 6-hydroxydopamine
hydrochloride (6-OHDA). Male Wistar rats, weighing 180-220 g, were induced
unilateral lesion at right substantia nigra by 6-OHDA and were orally given CP1
at doses of 100, 200, and 300 mg/kg body weight for 14 days after 6-OHDA
injection. The results showed that the 6-OHDA rats treated with CP1 increased
spatial memory, but decreased neurodegeneration, malondialdehyde level, and AChE
activity in hippocampus. The decreased motor disorder and neurodegeneration in
substantia nigra together with the enhanced catalase activity, but decreased MAO
B activity in striatum, were also observed. The memory enhancing effect of CP1
might occur through the improved oxidative stress and the enhanced cholinergic
function, whereas the effect to improve motor disorder of CP1 might occur through
the enhanced dopaminergic function in striatum by decreasing the degeneration of
dopaminergic neurons and the suppression of MAO-B. Therefore, CP1 is the
potential functional food against PD. However, further researches in clinical
trial and drug interactions are essential.
PMID- 26414360
TI - Retrospective cohort study of an enhanced recovery programme in oesophageal and
gastric cancer surgery.
AB - Introduction Enhanced recovery programmes have been established in some areas of
elective surgery. This study applied enhanced recovery principles to elective
oesophageal and gastric cancer surgery. Methods An enhanced recovery programme
for patients undergoing open oesophagogastrectomy, total and subtotal gastrectomy
for oesophageal and gastric malignancy was designed. A retrospective cohort study
compared length of stay on the critical care unit (CCU), total length of
inpatient stay, rates of complications and in-hospital mortality prior to (35
patients) and following (27 patients) implementation. Results In the cohort
study, the median total length of stay was reduced by 3 days following
oesophagogastrectomy and total gastrectomy. The median length of stay on the CCU
remained the same for all patients. The rates of complications and mortality were
the same. Conclusions The standardised protocol reduced the median overall length
of stay but did not reduce CCU stay. Enhanced recovery principles can be applied
to patients undergoing major oesophagogastrectomy and total gastrectomy as long
as they have minimal or reversible co-morbidity.
PMID- 26414362
TI - Effect of an independent-sector treatment centre on provision of elective
orthopaedic surgery in east and north Hertfordshire.
AB - Introduction Independent Sector Treatment Centres (ISTCs) were created to relieve
pressure from Acute Hospital Trusts. In October 2011, an ISTC opened on the
grounds of a hospital within the East and North Hertfordshire NHS Trust. Most
elective orthopaedic procedures were transferred there. We investigated the
effect on productivity of operating theatres working in the ISTC compared with
those working in the Acute Hospital Trust (AHT). Methods A 3-month period of
working at the AHT was compared with the same period 9-months later in the ISTC,
which were termed 'pre-' and 'post-ISTC' opening, respectively. Data for upper
limb (UL) as well as foot and ankle (F&A) surgery were collected. Differences in
the number of lists and patients per list constituted usage analyses. Financial
productivity was calculated from the latest Payment by Results (PbR) data. A two
tailed Mann-Whitney U-test at a confidence level of 95% was employed to compare
costs between groups. Results The UL surgeon undertook 18 lists in both years
with 66 patients (pre-ISTC) and 32 (post-ISTC), eliciting a reduction in
productivity of 51.5%. There were 13 lists for F&A surgery pre-ISTC with 67
procedures, and 20 lists with 49 patients post-ISTC. Allowing for the difference
in the number of lists, a reduction of 52.5% was noted. PbR analyses confirmed
productivity of L169,695 (pre-ISTC) and L95,760 (post-ISTC) at a loss of L73,935
for the UL surgeon. F&A data revealed L97,801 (pre-ISTC) and L91,960 (post-ISTC)
at a loss of L54,742 when correcting for the difference in the number of lists.
There was a combined reduction in potential financial productivity of L128,677
over 3 months or L514,708 over 1 year. Discussion Implementation of the ISTC was
detrimental to departmental efficiency, with <50% of the number of patients being
treated and a marked reduction in financial productivity.
PMID- 26414361
TI - Injection of botulinum toxin for the treatment of post-laryngectomy
pharyngoesophageal spasm-related disorders.
AB - Introduction Pharyngoesophageal spasm (PES) can cause dysphagia, central valve
leak (CVL), and dypshonia in post-laryngectomy patients. Botulinum toxin has been
used effectively for the treatment of PES, but data regarding patient-reported
outcomes and efficacy for CVL are limited. We evaluated the results of botox
injection for PES spasm using subjective and objective measures. Methods Data
were collected prospectively (February 2010 to August 2013) on 13 patients
undergoing botox injection for PES as identified by video fluoroscopy. We
collected digital voice recordings, air-pressure measurements (APMs) for speech,
and quality of life (QoL) data before and after the procedure: University of
Washington QoL questionnaire (UW-QoL), MD Anderson Swallowing Inventory (MDADI)
and the Voice Handicap Index (VHI-30). Results APMs for a sustained vowel
decreased by 18% after botox injection, whereas maximum phonatory times increased
by 63% (mean increase, 8 to 13 seconds). Sustained vowel amplitude decreased
(mean, 87db to 83db) with an associated reduction in sustained vowel frequency
(117Hz to 77Hz). MDADI scores improved by 10.2% overall, and UW-QoL scores showed
an improvement in score of 7.6%. Mean scores for VHI-30 deteriorated by 2%
overall but, when considering only those patients experiencing dysphonia, an
improvement of 9.4% was seen. There was an overall net reduction for the CVL
cohort of 12 speech valves in the year after injection. Conclusions Our series
confirm the safety and objective efficacy of botox injection for PES. QoL
measurements were less convincing, and this disparity between subjective and
objective measurements must be considered when treating such patients.
PMID- 26414363
TI - Rectus sheath catheters provide equivalent analgesia to epidurals following
laparotomy for colorectal surgery.
AB - Introduction Rectus sheath catheters (RSCs) are increasingly being used to
provide postoperative analgesia following laparotomy for colorectal surgery.
Little is known about their efficacy in comparison with epidural infusion
analgesia (EIA). They are potentially better as they avoid the recognised
complications associated with EIA. This study compares these two methods of
analgesia. Outcomes include average pain scores, time to mobilisation and length
of stay. Methods This was a 33-month single centre observational study including
all patients undergoing elective open or laparoscopic-converted-to-open
colorectal resection for both benign and malignant disease. Patients received
either EIA or RSCs. Data were collected prospectively and analysed
retrospectively. Results A total of 95 patients were identified. Indications for
surgery, operation and complications were recorded. The mean time to mobilisation
was significantly shorter in patients who had RSCs compared with EIA patients
(2.4 vs 3.5 days, p<0.05). There was no difference in postoperative pain scores
or length of stay. Conclusions RSCs provide equivalent analgesia to EIA and avoid
the recognised potential complications of EIA. They are associated with a shorter
time to mobilisation. Their use should be adopted more widely.
PMID- 26414365
TI - Reflections.
PMID- 26414366
TI - Recent NICE guidance of interest to surgeons.
PMID- 26414367
TI - Creating gelatine models for vascular access surgical courses.
PMID- 26414368
TI - The Wessex wrap circumcision dressing.
PMID- 26414369
TI - Femoral access for endovascular aneurysm repair in obese patients.
PMID- 26414370
TI - A novel technique for harvesting fat for breast augmentation.
PMID- 26414371
TI - Novel approach to drainage of a right subphrenic abscess using trans
diaphragmatic laparoscopy.
PMID- 26414372
TI - Doege-Potter Syndrome.
AB - Doege-Potter syndrome is a rare paraneoplastic syndrome presenting as a
hypoinsulinaemic hypoglycaemia from the ectopic secretion of a prohormone of
insulin-like growth factor II (IGF-II) from a solitary fibrous tumour. Surgical
resection is curative in the majority of cases. If, however, the diagnosis is not
suspected and treatment is delayed, it can lead to hypoxic cerebral injury or
death. The underlying tumour can be a benign or malignant pleural tumour but may
be present in extrapleural sites. For a diagnosis of Doege-Potter syndrome,
symptoms attributable to hypoglycaemia and low blood glucose levels should be
present along with the secretion of prohormone IGF-II. We report a case of severe
hypoglycaemia in a 76-year-old inpatient admitted for resection of a recurrent
left-sided pleural tumour. Investigation revealed true hypoglycaemia and Doege
Potter syndrome was diagnosed. The tumour was completely resected and the patient
made a full recovery with no further hypoglycaemic episodes.
PMID- 26414373
TI - Quantitative functional outcomes of the conservative management of partial
segmental thrombosis of the corpus cavernosum.
AB - The low incidence of partial segmental thrombosis of the corpus cavernosum
(PSTCC) means its management is guided by isolated case reports. Erectile
function is an important outcome that has not been described quantitatively in
the literature. We present two cases of PSTCC managed conservatively. Although
both patients reported resolution of local symptoms, formal analysis of sexual
function at follow-up review has revealed that only one achieved complete
recovery.
PMID- 26414377
TI - An ALE-based finite element model of flagellar motion driven by beating waves: A
parametric study.
AB - A computational model of flagellar motility is presented using the finite element
method. Two-dimensional traveling waves of finite amplitude are propagated down
the flagellum and the swimmer is propelled through a viscous fluid according to
Newto's second law of motion. Incompressible Navier-Stokes equations are solved
on a triangular moving mesh and arbitrary Lagrangian-Eulerian formulation is
employed to accommodate the deforming boundaries. The results from the present
study are validated against the data available in the literature and close
agreement with previous works is found. The effects of wave parameters as well as
head morphology on the swimming characteristics are studied for different
swimming conditions. We have found that the swimming velocities are linear
functions of finite amplitudes and that the rate of work is independent of the
channel height for large amplitudes. Furthermore, we have also demonstrated that
for the range of wave parameters that are often encountered in human sperm
motility studies, the propulsive velocity versus the wavelength exhibits
dissimilar trends for different channel heights. Various head configurations were
analyzed and it is also observed that wall proximity amplifies the effects
induced by different head shapes. By taking non-Newtonian fluids into account, we
present new efficiency analyzes through which we have found that the model
microorganism swims much more efficiently in shear-thinning fluids.
PMID- 26414376
TI - Excess Secretion of Gel-Forming Mucins and Associated Innate Defense Proteins
with Defective Mucin Un-Packaging Underpin Gallbladder Mucocele Formation in
Dogs.
AB - Mucosal protection of the gallbladder is vital yet we know very little about the
mechanisms involved. In domestic dogs, an emergent syndrome referred to as
gallbladder mucocele formation is characterized by excessive secretion of
abnormal mucus that results in obstruction and rupture of the gallbladder. The
cause of gallbladder mucocele formation is unknown. In these first mechanistic
studies of this disease, we investigated normal and mucocele-forming dog
gallbladders to determine the source, identity, biophysical properties, and
protein associates of the culprit mucins with aim to identify causes for abnormal
mucus behavior. We established that mucocele formation involves an adoptive
excess secretion of gel forming mucins with abnormal properties by the
gallbladder epithelium. The mucus is characterized by a disproportionally
significant increase in Muc5ac relative to Muc5b, defective mucin un-packaging,
and mucin-interacting innate defense proteins that are capable of dramatically
altering the physical and functional properties of mucus. These findings provide
an explanation for abnormal mucus behavior and based on similarity to mucus
observed in the airways of people with cystic fibrosis, suggest that abnormal
mechanisms for maintenance of gallbladder epithelial hydration may be an
instigating factor for mucocele formation in dogs.
PMID- 26414378
TI - A similarity-based data warehousing environment for medical images.
AB - A core issue of the decision-making process in the medical field is to support
the execution of analytical (OLAP) similarity queries over images in data
warehousing environments. In this paper, we focus on this issue. We propose
imageDWE, a non-conventional data warehousing environment that enables the
storage of intrinsic features taken from medical images in a data warehouse and
supports OLAP similarity queries over them. To comply with this goal, we
introduce the concept of perceptual layer, which is an abstraction used to
represent an image dataset according to a given feature descriptor in order to
enable similarity search. Based on this concept, we propose the imageDW, an
extended data warehouse with dimension tables specifically designed to support
one or more perceptual layers. We also detail how to build an imageDW and how to
load image data into it. Furthermore, we show how to process OLAP similarity
queries composed of a conventional predicate and a similarity search predicate
that encompasses the specification of one or more perceptual layers. Moreover, we
introduce an index technique to improve the OLAP query processing over images. We
carried out performance tests over a data warehouse environment that consolidated
medical images from exams of several modalities. The results demonstrated the
feasibility and efficiency of our proposed imageDWE to manage images and to
process OLAP similarity queries. The results also demonstrated that the use of
the proposed index technique guaranteed a great improvement in query processing.
PMID- 26414379
TI - Ex-Ante Economic Impact Assessment of Genetically Modified Banana Resistant to
Xanthomonas Wilt in the Great Lakes Region of Africa.
AB - BACKGROUND: Credible empirical evidence is scanty on the social implications of
genetically modified (GM) crops in Africa, especially on vegetatively propagated
crops. Little is known about the future success of introducing GM technologies
into staple crops such as bananas, which are widely produced and consumed in the
Great Lakes Region of Africa (GLA). GM banana has a potential to control the
destructive banana Xanthomonas wilt disease. OBJECTIVE: To gain a better
understanding of future adoption and consumption of GM banana in the GLA
countries which are yet to permit the production of GM crops; specifically, to
evaluate the potential economic impacts of GM cultivars resistant to banana
Xanthomonas wilt disease. DATA SOURCES: The paper uses data collected from
farmers, traders, agricultural extension agents and key informants in the GLA.
ANALYSIS: We analyze the perceptions of the respondents about the adoption and
consumption of GM crop. Economic surplus model is used to determine future
economic benefits and costs of producing GM banana. RESULTS: On the release of GM
banana for commercialization, the expected initial adoption rate ranges from 21
to 70%, while the ceiling adoption rate is up to 100%. Investment in the
development of GM banana is economically viable. However, aggregate benefits vary
substantially across the target countries ranging from US$ 20 million to 953
million, highest in countries where disease incidence and production losses are
high, ranging from 51 to 83% of production. CONCLUSION: The findings support
investment in the development of GM banana resistant to Xanthomonas wilt disease.
The main beneficiaries of this technology development are farmers and consumers,
although the latter benefit more than the former from reduced prices. Designing a
participatory breeding program involving farmers and consumers signifies the
successful adoption and consumption of GM banana in the target countries.
PMID- 26414380
TI - Blood Pressure Response to Losartan and Continuous Positive Airway Pressure in
Hypertension and Obstructive Sleep Apnea.
AB - RATIONALE: Obstructive sleep apnea (OSA) is common in people with hypertension,
particularly resistant hypertension. Treatment with an antihypertensive agent
alone is often insufficient to control hypertension in patients with OSA.
OBJECTIVES: To determine whether continuous positive airway pressure (CPAP) added
to treatment with an antihypertensive agent has an impact on blood pressure (BP)
levels. METHODS: During the initial 6-week, two-center, open, prospective, case
control, parallel-design study (2:1; OSA/no-OSA), all patients began treatment
with an angiotensin II receptor antagonist, losartan, 50 mg daily. In the second
6-week, sex-stratified, open, randomized, parallel-design study of the OSA group,
all subjects continued to receive losartan and were randomly assigned to either
nightly CPAP as add-on therapy or no CPAP. MEASUREMENTS AND MAIN RESULTS: Twenty
four-hour BP monitoring included assessment every 15 minutes during daytime hours
and every 20 minutes during the night. Ninety-one patients with untreated
hypertension underwent a home sleep study (55 were found to have OSA; 36 were
not). Losartan significantly reduced systolic, diastolic, and mean arterial BP in
both groups (without OSA: 12.6, 7.2, and 9.0 mm Hg; with OSA: 9.8, 5.7, and 6.1
mm Hg). Add-on CPAP treatment had no significant changes in 24-hour BP values but
did reduce nighttime systolic BP by 4.7 mm Hg. All 24-hour BP values were reduced
significantly in the 13 patients with OSA who used CPAP at least 4 hours per
night. CONCLUSIONS: Losartan reduced BP in OSA, but the reductions were less than
in no-OSA. Add-on CPAP therapy resulted in no significant changes in 24-hour BP
measures except in patients using CPAP efficiently. Clinical trial registered
with www.clinicaltrials.gov (NCT00701428).
PMID- 26414381
TI - Early events in hepatitis B virus infection: From the cell surface to the
nucleus.
AB - While most adults are able to clear acute hepatitis B virus (HBV) infection,
chronic HBV infection is recalcitrant to current therapy because of the
persistence of covalently closed circular DNA in the nucleus. Complete clearance
of the virus in these patients is rare, and long-term therapy with interferon
and/or nucleoside analogues may be required in an attempt to suppress viral
replication and prevent progressive liver damage. The difficulty of establishing
HBV infection in cell culture and experimental organisms has hindered efforts to
elucidate details of the HBV life cycle, but it has also revealed the importance
of the cellular microenvironment required for HBV binding and entry. Recent
studies have demonstrated an essential role of sodium-taurocholate cotransporting
polypeptide as a functional receptor in HBV infection, which has facilitated the
development of novel infection systems and opened the way for more detailed
understanding of the early steps of HBV infection as well as a potential new
therapeutic target. However, many gaps remain in understanding of how HBV
recognizes and attaches to hepatocytes prior to binding to sodium-taurocholate
cotransporting polypeptide, as well as events that are triggered after binding,
including entry into the cell, intracellular transport, and passage through the
nuclear pore complex. This review summarizes current knowledge of the initial
stages of HBV infection leading to the establishment of covalently closed
circular DNA in the nucleus.
PMID- 26414382
TI - Why does teaching research skills to family medicine trainees make sense?
AB - There are only a few countries in Europe that have incorporated research skills
training in specialty training programmes. In the eyes of most practising family
physicians, research traditionally is a field reserved for colleagues with
academic ambitions; an activity that often is not associated with the clinical
practice of family medicine. However, residents became aware that research is
essential to improving healthcare provision. Research in family medicine has a
long tradition. Performing or taking part in research projects opens new horizons
to present and future family physicians and provides support to increase their
self-esteem. Consequently, this could foster future family medicine development.
The authors urge the whole family physician community to raise the awareness
every single family physician towards teaching and learning research skills in
specialty training and basic medical education as a generic subject.
PMID- 26414383
TI - Evidence in the Age of Social Media.
PMID- 26414384
TI - Implications of Overdiagnosis: Impact on Screening Mammography Practices.
AB - This review article explores the issue of overdiagnosis in screening mammography.
Overdiagnosis is the screen detection of a breast cancer, histologically
confirmed, that might not otherwise become clinically apparent during the
lifetime of the patient. While screening mammography is an imperfect tool, it
remains the best tool we have to diagnose breast cancer early, before a patient
is symptomatic and at a time when chances of survival and options for treatment
are most favorable. In 2015, an estimated 231,840 new cases of breast cancer
(excluding ductal carcinoma in situ) will be diagnosed in the United States, and
some 40,290 women will die. Despite these data, screening mammography for women
ages 40-69 has contributed to a substantial reduction in breast cancer mortality,
and organized screening programs have led to a shift from late-stage diagnosis to
early-stage detection. Current estimates of overdiagnosis in screening
mammography vary widely, from 0% to upwards of 30% of diagnosed cancers. This
range reflects the fact that measuring overdiagnosis is not a straightforward
calculation, but usually one based on different sets of assumptions and often
biased by methodological flaws. The recent development of tomosynthesis, which
creates high-resolution, three-dimensional images, has increased breast cancer
detection while reducing false recalls. Because the greatest harm of
overdiagnosis is overtreatment, the key goal should not be less diagnosis but
better treatment decision tools. (Population Health Management 2015;18:S3-S11).
PMID- 26414385
TI - Identification and quantification of lichenysin - a possible source of food
poisoning.
AB - Lichenysin produced by 53 different Bacillus licheniformis strains has been
structurally examined with a qualitative liquid chromatography-tandem mass
spectrometry (LC-MS/MS) method using quadrupole-time-of-flight mass spectrometry.
The same lichenysin isoforms are produced from all strains, indicating that the
growth conditions have a stronger influence on the lipopeptide production than
the genotype. A rapid method for the quantification of lichenysin from bacterial
cell cultures with LC-MS/MS after a simple methanol extraction has been refined.
For the first time commercially available lichenysin has been used as calibrant,
making quantification more accurate. The trueness for C15-lichenysin has been
improved to 94% using matrix-matched calibration with lichenysin compared with
30% using solvent calibration with surfactin. The quantitative method was fully
validated based on Commission Decision 2002/657/EC. The LOD of the method was
below 1 ug g(-1) and the repeatability ranged from 10% to 16%.
PMID- 26414386
TI - Acute pain: a multifaceted challenge - the role of nimesulide.
AB - BACKGROUND: This article summarizes the outcome from an international consensus
meeting, which took place in Vienna on 4 November 2014. SCOPE: The aim of the
meeting was to provide the state of the art on the pathophysiology and treatment
of acute pain with special emphasis on nimesulide, a non-steroidal anti
inflammatory drug (NSAID) indicated for the treatment of acute pain and primary
dysmenorrhea. Besides the data on the mechanisms of acute inflammatory pain and
on the efficacy and safety of nimesulide in patients affected by different forms
of acute pain, the clinical experience of attending experts was discussed based
on selected case reports. RESULTS: The members of this consensus group recognized
that nimesulide is a NSAID highly effective in the treatment of several painful
situations with an acute inflammatory component including primary dysmenorrhea.
Although safety concerns regarding nimesulide have emerged in recent years, both
robust new epidemiological data and clinical experience confirm a positive
benefit/risk profile of nimesulide in the treatment of several forms of acute
pain. CONCLUSIONS: The members of this international consensus group concluded
that nimesulide, when used appropriately, remains a particularly valuable and
safe option for the treatment of several conditions characterized by the presence
of acute inflammatory pain because of the rapid onset of the analgesic action,
and the positive evidence-based benefit/risk profile.
PMID- 26414387
TI - Subdiffusion reflectance spectroscopy to measure tissue ultrastructure and
microvasculature: model and inverse algorithm.
AB - Reflectance measurements acquired from within the subdiffusion regime (i.e.,
lengthscales smaller than a transport mean free path) retain much of the original
information about the shape of the scattering phase function. Given this
sensitivity, many models of subdiffusion regime light propagation have focused on
parametrizing the optical signal through various optical and empirical
parameters. We argue, however, that a more useful and universal way to
characterize such measurements is to focus instead on the fundamental physical
properties, which give rise to the optical signal. This work presents the
methodologies that used to model and extract tissue ultrastructural and
microvascular properties from spatially resolved subdiffusion reflectance
spectroscopy measurements. We demonstrate this approach using ex-vivo rat tissue
samples measured by enhanced backscattering spectroscopy.
PMID- 26414388
TI - Anthropometric Renal Anatomic Alterations Between Supine and Prone Positions in
Percutaneous Renal Ablation for Renal Cortical Neoplasms.
AB - OBJECTIVES: To establish patterns of anatomic changes relevant to the kidney and
colon during positional change between the supine and prone positions as noted on
CT scans performed during percutaneous cryoablation for renal cortical neoplasms
(RCN). METHODS: Nineteen patients undergoing percutaneous cryoablation for RCN
with abdominal CT scan in both the supine and prone positions were included in
the study. We documented the anterior/posterior, medial/lateral, and
cranial/caudal anatomic changes of the kidney, kidney rotation, and the
proportion of the kidney whose access was limited by the liver, spleen, and lung.
We also calculated the length of the percutaneous access tract and the distance
between the colon and kidney in hilar position as well as the anterior/posterior
location of the colon relative to the kidney. RESULTS: In the prone position, the
kidney lies significantly more anteriorly on both sides: 4.7 cm vs 4.3 cm (L) and
4.4 cm vs 4.1 cm (R) (p = 0.02 and p = 0.03, respectively). On prone CT images,
both kidneys are more cranial when compared with the supine position: 80.4 mm vs
60.8 mm (L) and 87.2 mm vs 57.4 mm (R) (p = 0.002 and p < 0.001, respectively).
The skin to tumor distance is significantly shorter in the prone position (p <
0.0001 [L], p = 0.005 [R]). The colon lies closer to the hilum of the kidney and
is more posteriorly located in the prone position: 1.21 cm vs 1.04 cm (L) and
0.80 cm vs 0.70 cm (R) (p = 0.005 and p = 0.005, respectively). In the prone
position, the lung covers a significantly larger proportion of the right kidney
(27.3 mm vs 6.05 mm, p = 0.0001). CONCLUSIONS: We documented clinically
significant anatomic alterations between supine and prone CT imaging. The changes
associated with the prone position modify percutaneous access, particularly for
right upper pole tumors. Prone imaging before surgery may be helpful in selected
cases.
PMID- 26414389
TI - Genomic confirmation of nutrient-dependent mutability of mutators in Escherichia
coli.
AB - Mutators with increased mutation rates are prevalent in various environments and
have important roles in accelerating adaptive evolution. Previous studies on
mutator strains of microorganisms have shown that some mutators have constant
mutation rates, whereas others exhibit switchable mutation rates depending on
nutritional conditions. This suggests that the contributions of mutators on
evolution vary with fluctuating nutritional conditions. However, such conditional
mutability has been unclear at the genomic level. In addition, it is still
unknown why mutation rates change with nutritional condition. Here, we used two
mutator strains of Escherichia coli to explore the nutrient dependence of
mutation rates at the genomic level. These strains were transferred repeatedly
under different nutritional conditions for hundreds of generations to accumulate
mutations. Whole-genome sequencing of the offspring showed that the nutrient
dependence of the mutation rates was pervasive at the genomic scale. Neutrality
in the mutation accumulation processes and constancy in the mutational bias
suggested that nutrient dependence was not derived from conditional selective
purges or from shifts of mutational bias. Some mutators could simply switch their
mutation rates for both transitions and transversions in response to nutritional
shifts.
PMID- 26414396
TI - Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence:
Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes.
AB - The intrinsic properties of quantum dots (QDs) and the growing ability to
interface them controllably with living cells has far-reaching potential
applications in probing cellular processes such as membrane action potential. We
demonstrate that an electric field typical of those found in neuronal membranes
results in suppression of the QD photoluminescence (PL) and, for the first time,
that QD PL is able to track the action potential profile of a firing neuron with
millisecond time resolution. This effect is shown to be connected with electric
field-driven QD ionization and consequent QD PL quenching, in contradiction with
conventional wisdom that suppression of the QD PL is attributable to the quantum
confined Stark effect.
PMID- 26414398
TI - Turning a New Leaf on Metal-TMC Chemistry: Ni(II)(TMC) Acetylides.
AB - Novel [Ni(TMC)C=CY](+)-type compounds 1-4 [TMC = 1,4,8,11-tetramethyl-1,4,8,11
tetraazacyclotetradecane; Y = SiMe3 (1), Si(i)Pr3 (2), Ph (3), and C2H (4)] have
been synthesized and characterized. Single-crystal X-ray diffraction studies
revealed that these compounds adopt a distorted square-pyramidal geometry, with
the acetylide ligand occupying the apical position and a RSRS isomer for the TMC
ligand. The room temperature magnetic properties of 1-4 are consistent with an S
= 1 ground state, as corroborated by CASSCF and density functional theory
calculations, which indicate that the singly occupied molecular orbitals are
d(z(2)) and d(x(2)-y(2)).
PMID- 26414397
TI - Screening and Brief Alcohol Counseling of College Students and Persons Not in
School.
PMID- 26414399
TI - Growth arrest-specific 6 regulates thrombin-induced expression of vascular cell
adhesion molecule-1 through forkhead box O1 in endothelial cells.
AB - BACKGROUND: Growth arrest-specific 6 (Gas6)-deficient mice are protected against
venous thromboembolism (VTE), suggesting a role for Gas6 in this disorder. We
previously demonstrated that Gas6 induces forkhead box O1 (FoxO-1)
phosphorylation through the phosphoinositide 3-kinase-Akt pathway. FoxO-1
regulates the expression of vascular cell adhesion molecule-1 (VCAM-1), a
molecule that has been implicated in VTE. OBJECTIVES: To assess the role of FoxO
1 in Gas6-dependent VCAM-1 expression. METHODS: Thrombin was used to stimulate
endothelial cells (ECs). Wild-type (WT) and Gas6(-/-) ECs were transfected with
small interfering RNA targeting Axl or FoxO-1, a luciferase-coupled plasmid
containing the FoxO-1 consensus sequence, and a phosphorylation-resistant FoxO-1
mutant, or treated with an Akt inhibitor. VCAM-1 mRNA expression was measured by
real time-qPCR. VCAM-1 protein expression and FoxO-1 and Akt phosphorylation were
assessed by western blot analysis. FoxO-1 localization was assessed by
immunofluorescence. Adhesion of bone marrow mononuclear cells (BM-MCs) on ECs was
assessed by fluorescence. RESULTS AND CONCLUSIONS: Thrombin induces both VCAM-1
expression and FoxO-1 phosphorylation and nuclear exclusion in WT ECs only.
Silencing of FoxO-1 enhances VCAM-1 expression in both WT and Gas6(-/-) ECs.
Inhibition of Akt or FoxO-1 phosphorylation prevents VCAM-1 expression in WT ECs.
These data show that Gas6 induces FoxO-1 phosphorylation, leading to derepression
of VCAM-1 expression. BM-MC-EC adhesion is increased by thrombin in WT ECs. BM-MC
EC adhesion is further increased when FoxO-1 is silenced, but decreased when FoxO
1 phosphorylation is inhibited. These results demonstrate that the Gas6-FoxO-1
signaling axis plays an important role in VCAM-1 expression in the context of VTE
by promoting BM-MC-EC adhesion.
PMID- 26414400
TI - Behavior modulation of rats to a robotic rat in multi-rat interaction.
AB - In this paper, we study the behavioral response of rats to a robotic rat during
multi-rat interaction. Experiments are conducted in an open-field where a robotic
rat called WR-5 is put together with three laboratory rats. WR-5 is following one
rat (target), while avoiding the other two rats (outside observers) during
interaction. The behavioral characteristics of each target rat is evaluated by
scoring its locomotor activity and frequencies of performing rearing, body
grooming and mounting actions. Additionally, the frequency of being mounted by
other rats is also measured. Experimental results show that the target becomes
more active after interaction. The rat species, with more active behavioral
characteristics, is more susceptible to being adjusted by the robot. The
increased time spent by the outside observers in the vicinity of the robot
indicates that a biomimetic robot has the promise for modulating rat behavior
even without direct interaction. Thus, this study provide a novel approach to
shaping the sociality of animals living in groups.
PMID- 26414401
TI - The Aryl Hydrocarbon Receptor Antagonist StemRegenin1 Improves In Vitro
Generation of Highly Functional Natural Killer Cells from CD34(+) Hematopoietic
Stem and Progenitor Cells.
AB - Early natural killer (NK)-cell repopulation after allogeneic stem cell
transplantation (allo-SCT) has been associated with reduced relapse rates without
an increased risk of graft-versus-host disease, indicating that donor NK cells
have specific antileukemic activity. Therefore, adoptive transfer of donor NK
cells is an attractive strategy to reduce relapse rates after allo-SCT. Since NK
cells of donor origin will not be rejected, multiple NK-cell infusions could be
administered in this setting. However, isolation of high numbers of functional NK
cells from transplant donors is challenging. Hence, we developed a cytokine-based
ex vivo culture protocol to generate high numbers of functional NK cells from
granulocyte colony-stimulating factor (G-CSF)-mobilized CD34(+) hematopoietic
stem and progenitor cells (HSPCs). In this study, we demonstrate that addition of
aryl hydrocarbon receptor antagonist StemRegenin1 (SR1) to our culture protocol
potently enhances expansion of CD34(+) HSPCs and induces expression of NK-cell
associated transcription factors promoting NK-cell differentiation. As a result,
high numbers of NK cells with an active phenotype can be generated using this
culture protocol. These SR1-generated NK cells exert efficient cytolytic activity
and interferon-gamma production toward acute myeloid leukemia and multiple
myeloma cells. Importantly, we observed that NK-cell proliferation and function
are not inhibited by cyclosporin A, an immunosuppressive drug often used after
allo-SCT. These findings demonstrate that SR1 can be exploited to generate high
numbers of functional NK cells from G-CSF-mobilized CD34(+) HSPCs, providing
great promise for effective NK-cell-based immunotherapy after allo-SCT.
PMID- 26414402
TI - Complementary activities of TPX2 and chTOG constitute an efficient importin
regulated microtubule nucleation module.
AB - Spindle assembly and function require precise control of microtubule nucleation
and dynamics. The chromatin-driven spindle assembly pathway exerts such control
locally in the vicinity of chromosomes. One of the key targets of this pathway is
TPX2. The molecular mechanism of how TPX2 stimulates microtubule nucleation is
not understood. Using microscopy-based dynamic in vitro reconstitution assays
with purified proteins, we find that human TPX2 directly stabilizes growing
microtubule ends and stimulates microtubule nucleation by stabilizing early
microtubule nucleation intermediates. Human microtubule polymerase chTOG
(XMAP215/Msps/Stu2p/Dis1/Alp14 homologue) only weakly promotes nucleation, but
acts synergistically with TPX2. Hence, a combination of distinct and
complementary activities is sufficient for efficient microtubule formation in
vitro. Importins control the efficiency of the microtubule nucleation by
selectively blocking the interaction of TPX2 with microtubule nucleation
intermediates. This in vitro reconstitution reveals the molecular mechanism of
regulated microtubule formation by a minimal nucleation module essential for
chromatin-dependent microtubule nucleation in cells.
PMID- 26414403
TI - Competition for actin between two distinct F-actin networks defines a bistable
switch for cell polarization.
AB - Symmetry-breaking polarization enables functional plasticity of cells and tissues
and is yet not well understood. Here we show that epithelial cells, hard-wired to
maintain a static morphology and to preserve tissue organization, can
spontaneously switch to a migratory polarized phenotype after relaxation of the
actomyosin cytoskeleton. We find that myosin II engages actin in the formation of
cortical actomyosin bundles and thus makes it unavailable for deployment in the
process of dendritic growth normally driving cell motility. Under low
contractility regimes, epithelial cells polarize in a front-back manner owing to
the emergence of actin retrograde flows powered by dendritic polymerization of
actin. Coupled to cell movement, the flows transport myosin II from the front to
the back of the cell, where the motor locally 'locks' actin in contractile
bundles. This polarization mechanism could be employed by embryonic and cancer
epithelial cells in microenvironments where high-contractility-driven cell motion
is inefficient.
PMID- 26414404
TI - Lateral adhesion drives reintegration of misplaced cells into epithelial
monolayers.
AB - Cells in simple epithelia orient their mitotic spindles in the plane of the
epithelium so that both daughter cells are born within the epithelial sheet. This
is assumed to be important to maintain epithelial integrity and prevent
hyperplasia, because misaligned divisions give rise to cells outside the
epithelium. Here we test this assumption in three types of Drosophila epithelium;
the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the
pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these
tissues reorients mitotic spindles, resulting in one daughter cell being born
outside the epithelial layer. Live imaging reveals that these misplaced cells
reintegrate into the tissue. Reducing the levels of the lateral homophilic
adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise
to extra-epithelial cells, whereas disruption of adherens junctions has no
effect. Thus, the reinsertion of misplaced cells seems to be driven by lateral
adhesion, which pulls cells born outside the epithelial layer back into it. Our
findings reveal a robust mechanism that protects epithelia against the
consequences of misoriented divisions.
PMID- 26414405
TI - Depression-like behaviour in mice is associated with disrupted circadian rhythms
in nucleus accumbens and periaqueductal grey.
AB - An association between circadian rhythms and mood regulation is well established,
and disturbed circadian clocks are believed to contribute to the development of
mood disorders, including major depressive disorder. The circadian system is
coordinated by the suprachiasmatic nucleus (SCN), the master pacemaker in the
hypothalamus that receives light input from the retina and synchronizes circadian
oscillators in other brain regions and peripheral tissues. Lacking the tight
neuronal network that couples single-cell oscillators in the SCN, circadian
clocks outside the SCN may be less stable and more susceptible to disturbances,
for example by clock gene mutations or uncontrollable stress. However, non-SCN
circadian clocks have not been studied extensively in rodent models of mood
disorders. In the present study, it was hypothesized that disturbances of local
circadian clocks in mood-regulating brain areas are associated with depression
like behaviour in mice. Using the learned helplessness procedure, depression-like
behaviour was evoked in mice bearing the PER2::LUC circadian reporter, and then
circadian rhythms of PER2 expression were examined in brain slices from these
mice using luminometry and bioluminescence imaging. It was found that
helplessness is associated with absence of circadian rhythms in the nucleus
accumbens and the periaqueductal grey, two of the most critical brain regions
within the reward circuit. The current study provides evidence that
susceptibility of mice to depression-like behaviour is associated with disturbed
local circadian clocks in a subset of mood-regulating brain areas, but the
direction of causality remains to be determined.
PMID- 26414406
TI - The first reported outbreak of equine herpesvirus myeloencephalopathy in New
Zealand.
AB - CASE HISTORY AND CLINICAL FINDINGS: On 9 January 2014 (Day 0) a mare from a stud
farm in the Waikato region presented with urinary incontinence without pyrexia.
Over the following 33 days 15 mares were clinically affected with neurological
signs. All but one mare had a foal at foot. The most commonly observed clinical
signs were hind limb paresis and ataxia. In some cases recumbency occurred very
early in the course of disease and seven mares were subject to euthanasia for
humane reasons. LABORATORY FINDINGS: Equid herpesvirus (EHV) type 1 was detected
using PCR in various tissues collected post mortem from two mares with
neurological signs. DNA sequencing data from the DNA polymerase gene of the virus
showed a nucleotide transition at position 2254, a mutation encoding amino acid
D752 that is highly associated with the neuropathogenic genotype of EHV-1. In
total 12/15 mares were confirmed positive for EHV-1 on PCR. Results from a virus
neutralisation test and ELISA on paired serum samples, and PCR on whole blood and
nasal swabs, indicated that of four paddocks in a high-risk area where a cluster
of cases had occurred, 20/21 (95%) horses were likely to have been exposed or
were confirmed infected with EHV-1. Subsequent to the outbreak two mares aborted,
one at 9 months and one at 10 months of gestation. The cause of abortion was
confirmed as EHV-1 with the same genotype as that involved in the outbreak.
DIAGNOSIS: Equine herpesvirus myeloencephalopathy. CLINICAL RELEVANCE: The
outbreak described shows the considerable impact that can occur in outbreaks of
equine herpesvirus myeloencephalopathy in New Zealand. Early biosecurity controls
not only reduced the effect on the farm but mitigated the potential for the virus
to spread to other horse enterprises.
PMID- 26414407
TI - Into the groove: instructive silk-polypyrrole films with topographical guidance
cues direct DRG neurite outgrowth.
AB - Instructive biomaterials capable of controlling the behaviour of the cells are
particularly interesting scaffolds for tissue engineering and regenerative
medicine. Novel biomaterials are particularly important in societies with rapidly
aging populations, where demand for organ/tissue donations is greater than their
supply. Herein we describe the preparation of electrically conductive silk film
based nerve tissue scaffolds that are manufactured using all aqueous processing.
Aqueous solutions of Bombyx mori silk were cast on flexible polydimethylsiloxane
substrates with micrometer-scale grooves on their surfaces, allowed to dry, and
annealed to impart beta-sheets to the silk which assures that the materials are
stable for further processing in water. The silk films were rendered conductive
by generating an interpenetrating network of polypyrrole and polystyrenesulfonate
in the silk matrix. Films were incubated in an aqueous solution of pyrrole
(monomer), polystyrenesulfonate (dopant) and iron chloride (initiator), after
which they were thoroughly washed to remove low molecular weight components
(monomers, initiators, and oligomers) and dried, yielding conductive films with
sheet resistances of 124 +/- 23 kOmega square(-1). The micrometer-scale grooves
that are present on the surface of the films are analogous to the natural
topography in the extracellular matrix of various tissues (bone, muscle, nerve,
skin) to which cells respond. Dorsal root ganglions (DRG) adhere to the films and
the grooves in the surface of the films instruct the aligned growth of processes
extending from the DRG. Such materials potentially enable the electrical
stimulation (ES) of cells cultured on them, and future in vitro studies will
focus on understanding the interplay between electrical and topographical cues on
the behaviour of cells cultured on them.
PMID- 26414408
TI - Intratympanic delivery of oligoarginine-conjugated nanoparticles as a gene (or
drug) carrier to the inner ear.
AB - A drug delivery system to the inner ear using nanoparticles consisting of
oligoarginine peptide (Arg8) conjugated to poly(amino acid) (poly(2-hydroxyethyl
L-aspartamide; PHEA) was investigated to determine whether the limitations of low
drug transport levels across the round window membrane (RWM) and poor transport
into inner ear target cells, including hair cells and spiral ganglion, could be
overcome. Three types of carrier materials, PHEA-g-C18, PHEA-g-Arg8, and PHEA-g
C18-Arg8, were synthesized to examine the effects of oligoarginine and morphology
of the synthesized carriers. Nile red (NR) was used as a fluorescent indicator as
well as to model a hydrophobic drug. Compared with PHEA-g-C18-NR nanoparticles,
the oligoarginine-conjugated nanoparticles of PHEA-g-C18-Arg8-NR and PHEA-g-Arg8
NR entered into HEI-OC1 cells at significant levels. Furthermore, the strongest
fluorescence intensity was observed in nuclei when PHEA-g-C18-Arg8 nanoparticles
were used. The high uptake rates of PHEA-g-C18 and PHEA-g-C18-Arg8 nanoparticles
were observed in ex vivo experiments using hair cells. After the delivery of PHEA
g-C18-Arg8 nanoparticles with reporter gene transfer, EGFP (enhanced green
fluorescent protein) expression was monitored as an indicator of gene delivery.
In the inner ear cells, PHEA-g-C18-Arg8 nanoparticles showed comparable or better
transfection capabilities than the commercially available Lipofectamine reagent.
PHEA-g-C18-Arg8 penetrated in vivo across the RWM of C57/BL6 mice with Nile red
staining and GFP expression in various inner ear tissues. In conclusion, PHEA-g
C18-Arg8 nanoparticles were successfully transported into the inner ear through
the intratympanic route and are proposed as promising candidates as delivery
carriers to address inner ear diseases.
PMID- 26414410
TI - Association of Visceral Fat and Liver Fat With Hyperuricemia.
AB - OBJECTIVE: To examine cross-sectionally whether intraabdominal fat area (IAFA),
i.e., visceral fat, and liver fat assessed by computed tomography (CT) are
independently associated with hyperuricemia. METHODS: Subjects were 801 Japanese
men not taking antidiabetic, antihypertensive, or urate-lowering medications,
without any history of renal disease, cardiovascular disease, or cancer, and with
serum creatinine <1.5 mg/dl. Abdominal, thoracic, and thigh fat areas were
measured by CT. Total fat area (TFA) was the sum of these fat areas. Total
subcutaneous fat area (TSFA) was TFA minus IAFA. Liver fat was assessed by liver
to-spleen (L/S) ratio measured by CT. Hyperuricemia was defined as serum uric
acid level >7.0 mg/dl. Its association with adiposity was tested using logistic
regression. RESULTS: The prevalence of hyperuricemia was 19.6% (157 men). Both
greater IAFA and lower L/S ratio were independently associated with hyperuricemia
in models that simultaneously included IAFA and L/S ratio: multiple-adjusted odds
ratios of hyperuricemia for quintiles 3, 4, and 5 of IAFA were 2.16 (95%
confidence interval [95% CI] 1.02-4.59), 2.41 (95% CI 1.13-5.16), and 4.00 (95%
CI 1.81-8.85), respectively, compared to quintile 1, and the L/S ratios for
quintiles 3, 2, and 1 were 2.34 (95% CI 1.16-4.75), 2.15 (95% CI 1.06-4.34), and
2.79 (95% CI 1.35-5.76), respectively, compared to quintile 5. Both IAFA and L/S
ratio remained significant even after adjusting for abdominal subcutaneous fat
area, TFA, TSFA, body mass index, or waist circumference. Of all fat
measurements, IAFA had the strongest association with hyperuricemia by Akaike's
information criteria. CONCLUSION: Greater amounts of both visceral fat and liver
fat were independently associated with hyperuricemia.
PMID- 26414409
TI - Synthesis, properties, and biomedical applications of gelatin methacryloyl
(GelMA) hydrogels.
AB - Gelatin methacryloyl (GelMA) hydrogels have been widely used for various
biomedical applications due to their suitable biological properties and tunable
physical characteristics. GelMA hydrogels closely resemble some essential
properties of native extracellular matrix (ECM) due to the presence of cell
attaching and matrix metalloproteinase responsive peptide motifs, which allow
cells to proliferate and spread in GelMA-based scaffolds. GelMA is also versatile
from a processing perspective. It crosslinks when exposed to light irradiation to
form hydrogels with tunable mechanical properties. It can also be microfabricated
using different methodologies including micromolding, photomasking, bioprinting,
self-assembly, and microfluidic techniques to generate constructs with controlled
architectures. Hybrid hydrogel systems can also be formed by mixing GelMA with
nanoparticles such as carbon nanotubes and graphene oxide, and other polymers to
form networks with desired combined properties and characteristics for specific
biological applications. Recent research has demonstrated the proficiency of
GelMA-based hydrogels in a wide range of tissue engineering applications
including engineering of bone, cartilage, cardiac, and vascular tissues, among
others. Other applications of GelMA hydrogels, besides tissue engineering,
include fundamental cell research, cell signaling, drug and gene delivery, and
bio-sensing.
PMID- 26414412
TI - Enhancing antimicrobial activity of TiO2/Ti by torularhodin bioinspired surface
modification.
AB - Implant-associated infections are a major cause of morbidity and mortality. This
study was performed using titanium samples coated by anodization with a titanium
dioxide (TiO2) shielded nanotube layer. TiO2/Ti surface was modified by simple
immersion in torularhodin solution and by using a mussel-inspired method based on
polydopamine as bio adhesive for torularhodin immobilization. SEM analysis
revealed tubular microstructures of torularhodin and the PDA ability to function
as a catchy anchor between torularhodin and TiO2 surface. Corrosion resistance
was associated with TiO2 barrier oxide layer and nano-organized oxide layer and
the torularhodin surface modification does not bring significant changes in
resistance of the oxide layer. Our results demonstrated that the torularhodin
modified TiO2/Ti surface could effectively prevent adhesion and proliferation of
Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Bacillus
subtilis, and Pseudomonas aeruginosa. The new modified titanium surface showed
good biocompatibility and well-behaved haemocompatibility. This biomaterial with
enhanced antimicrobial activity holds great potential for future biomedical
applications.
PMID- 26414411
TI - Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus.
AB - Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC)
proliferation in the hippocampal dentate gyrus. However, various groups have
reported contradictory results on whether TBI increases neurogenesis, partially
due to a wide range in the severities of injuries seen with different TBI models.
To address whether the severity of TBI affects neurogenesis in the injured brain,
we assessed neurogenesis in mouse brains receiving different severities of
controlled cortical impact (CCI) with the same injury device. The mice were
subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI
severity on neurogenesis were evaluated at three stages: NSC proliferation,
immature neurons, and newly-generated mature neurons. The results showed that
mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI
promoted NSC proliferation without increasing neurogenesis. Severe TBI increased
neurogenesis at all three stages. Our data suggest that the severity of injury
affects adult neurogenesis in the hippocampus, and thus it may partially explain
the inconsistent results of different groups regarding neurogenesis following
TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide
a potential approach for using endogenous NSCs to protect against neuronal loss
after trauma.
PMID- 26414414
TI - Coral-the world's most diverse symbiotic ecosystem.
AB - Zooxanthellate corals (i.e. those harbouring Symbiodinium) are the main builders
of the world's shallow-water marine coral reefs. They represent intimate diverse
symbioses between coral animals, single-celled photosynthetic dinoflagellates
(Symbiodinium spp.), other microscopic eukaryotes, prokaryotes and viruses. Crabs
and other crustaceans, worms, sponges, bivalves and hydrozoans, fishes, sea
urchins, octopuses and sea stars are itinerant members of these 'rainforests of
the sea'. This review focuses on the biodiversity of scleractinian coral animals
and their best studied microscopic epi- and endosymbionts. In relation to coral
associated species diversity, Symbiodinium internal transcribed spacer region
sequence types tally 10(2) -10(3) or up to ~15 different operational taxonomic
units (OTUs, or putative species at the 97% sequence identity level; this cut-off
was chosen based on intragenomic sequence diversity observed in monoclonal
cultures) and prokaryotes (mostly bacterial) total 10(2) -10(4) OTUs. We analysed
all publically accessible 16S rRNA gene sequence data and found
Gammaproteobacteria were extremely abundant, followed by Alphaproteobacteria.
Notably, Archaea were poorly represented and 'unassigned OTUs' were abundant in
data generated by high-throughput DNA sequencing studies of corals. We outline
and compare model systems that could be used in future studies of the coral
holobiont. In our future directions, we recommend a global coral sampling effort
including substantial attention being paid to method of coral tissue acquisition,
which compartments (mucus, tissue, skeleton) to explore, broadening the holobiont
members considered and linking biodiversity with functional investigations.
PMID- 26414415
TI - ALSUntangled No. 31: Protandim.
PMID- 26414416
TI - Understanding affiliate stigma faced by heterosexual family and friends of LGB
people: A measurement development study.
AB - The present study describes the development and psychometric evaluation of the
Lesbian, Gay, Bisexual Affiliate Stigma Measure (LGB-ASM). Existing qualitative
research and feedback from experts in stigma research contributed to the
development of 48 items that were subjected to psychometric evaluation resulting
in the final 17-item measure. Exploratory factor analysis of data from 471 LGB
affiliates (family members and close friends of LGB individuals) resulted in 3
factors reflecting experiences of LGB affiliate stigma including (a) public
discrimination/rejection affiliate stigma, (b) vicarious affiliate stigma, and
(c) public shame affiliate stigma. Confirmatory factor analysis of data from a
separate 101 participants supported the stability of the 3-factor model. Further
psychometric evaluation of the measure resulted in evidence supporting the
reliability (i.e., Cronbach's alphas of .71 to .93), convergent validity (i.e.,
with stigma consciousness, r = .17 to .45; with awareness of public devaluation,
r = .18 to .28), and discriminant validity (i.e., with socially desirable
responding, r = -.16 to .05). The final 17-item LGB-ASM yielded 2-to 3-week test
retest reliability coefficients of .74 to .76 with a sample of 61 participants.
Exploratory links between the LGB-ASM and psychological distress (using the
Hopkins Symptom Checklist-21) were evaluated.
PMID- 26414413
TI - A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary
Overpressure Blast to the Cranium in Mice.
AB - Mild traumatic brain injury (TBI) from focal head impact is the most common form
of TBI in humans. Animal models, however, typically use direct impact to the
exposed dura or skull, or blast to the entire head. We present a detailed
characterization of a novel overpressure blast system to create focal closed-head
mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on
the left side of the head overlying the forebrain is delivered to anesthetized
mice. The mouse eyes and ears are shielded, and its head and body are cushioned
to minimize movement. This approach creates mild TBI by a pressure wave that acts
on the brain, with minimal accompanying head acceleration-deceleration. A single
20-psi blast yields no functional deficits or brain injury, while a single 25-40
psi blast yields only slight motor deficits and brain damage. By contrast, a
single 50-60 psi blast produces significant visual, motor, and neuropsychiatric
impairments and axonal damage and microglial activation in major fiber tracts,
but no contusive brain injury. This model thus reproduces the widespread axonal
injury and functional impairments characteristic of closed-head mild TBI, without
the complications of systemic or ocular blast effects or head acceleration that
typically occur in other blast or impact models of closed-skull mild TBI.
Accordingly, our model provides a simple way to examine the biomechanics,
pathophysiology, and functional deficits that result from TBI and can serve as a
reliable platform for testing therapies that reduce brain pathology and deficits.
PMID- 26414417
TI - The role of parental warmth and hostility on adolescents' prosocial behavior
toward multiple targets.
AB - The current study examined the influence that parental warmth/support and verbal
hostility had on adolescents' prosocial behavior toward multiple targets
(stranger, friend, family) using multiple reporters (self, parent, observations).
Data were taken from Times 2 and 3 of a longitudinal project and included 500
adolescents and their parents (M age of child at Time 2 = 12.34). Structural
equation models suggested that mother warmth was associated with prosocial
behavior toward family, while father warmth was associated with prosocial
behavior toward friends. Findings also suggested that adolescents' prosocial
behavior was more consistently influenced by father hostility than it was by
father warmth. Finally, observational reports of father hostility were associated
with adolescent prosocial behavior more consistently than self- or child-reported
parenting. The discussion focuses on the importance of considering target of
prosocial behavior, the differences between mothers and fathers, and the role of
self-reports compared to observations.
PMID- 26414418
TI - Preventing adolescent depression with the family check-up: Examining family
conflict as a mechanism of change.
AB - Family-centered prevention programs are understudied for their effects on
adolescent depression, despite considerable evidence that supports their
effectiveness for preventing escalation in youth problem behavior and substance
use. This study was conducted with 2 overarching goals: (a) replicate previous
work that has implicated the Family Check-Up (FCU), a multilevel, gated
intervention model embedded in public middle schools, as an effective strategy
for preventing growth in adolescent depressive symptoms and (b) test whether
changes in family conflict may be an explanatory mechanism for the long-term,
protective effects of the FCU with respect to adolescent depression. This trial
was conducted with 593 ethnically diverse families who were randomized to
intervention (offered the FCU) or middle school as usual. Complier average causal
effect (CACE) analysis revealed that engagers in the FCU evidenced less growth in
depressive symptoms and family conflict from 6th through 9th grade, and post hoc
analyses indicated that the FCU is related to lower rates of major depressive
disorder. The second set of analyses examined family conflict as a mechanism of
change for families who participated in the FCU. Families who reported short-term
intervention benefits had significantly less escalation in family conflict over
the middle school years; in turn, growth in family conflict explained risk for
adolescent depressive symptoms.
PMID- 26414420
TI - Controlling optical properties of metallic multi-shell nanoparticles through
suppressed surface plasmon resonance.
AB - Herein, we report the surface plasmon resonance of plasmonic multi-shell
nanoparticles compared to bimetallic Ag/Au hollow nanospheres of similar final
size, shape, and percent composition. The surface plasmon resonance of solid and
hollow nanoparticles exhibited a quadrupole mode that was particularly prominent
around the 100 nm size regime, while multi-shell nanoparticles did not show a
quadrupole mode at a similar size. In the latter case, the quadrupole mode of the
outermost nanoshell was suppressed by the dipole modes of the inner shells, and
the suppression of the quadrupole mode was not affected by the shape of the inner
nanostructures. Light interaction of the multi-shell nanoparticle was
investigated through simulated electromagnetic field distribution obtained by
finite-difference time domain (FDTD) calculations which were in a good agreement
with the results of surface-enhanced Raman spectroscopy (SERS).
PMID- 26414419
TI - Controllable in situ synthesis of silver nanoparticles on multilayered film
coated silk fibers for antibacterial application.
AB - Layer-by-layer (LbL) assembly is a versatile technique for the preparation of
multilayered polymeric films. However, fabrication of LbL polymetic film on silk
for the in situ growth of high-density silver nanoparticles (AgNPs) has not been
realized. Herein poly(acrylic acid) (PAA)/poly(dimethyldiallylammonium chloride)
(PDDA) multilayers are constructed on silk via the LbL approach, subsequently
serving as a 3-dimensional matrix for in situ synthesis of AgNPs. After 8 rounds
of LbL assembly, the silk is fully covered with a layer of polymeric film. AgNPs
with good crystalline structures could be in-situ generated in the silk-coated
multilayers and their amount could be tailored by adjusting the bilayer numbers.
The as-prepared silk could effectively kill the existing bacteria and inhibit the
bacterial growth, demonstrating the antimicrobial activity. Moreover, the release
of Ag(+) from the modified silk can last for 120 h, rendering the modified silk
sustainable antimicrobial activity. This work may provide a novel method to
prepare AgNPs-functionalized antimicrobial silk for potential applications in
textile industry.
PMID- 26414421
TI - Viscosity and stability of ultra-high internal phase CO2-in-water foams
stabilized with surfactants and nanoparticles with or without polyelectrolytes.
AB - To date, relatively few examples of ultra-high internal phase supercritical CO2
in-water foams (also referred to as macroemulsions) have been observed, despite
interest in applications including "waterless" hydraulic fracturing in energy
production. The viscosities and stabilities of foams up to 0.98 CO2 volume
fraction were investigated in terms of foam bubble size, interfacial tension, and
bulk and surface viscosity. The foams were stabilized with laurylamidopropyl
betaine (LAPB) surfactant and silica nanoparticles (NPs), with and without
partially hydrolyzed polyacrylamide (HPAM). For foams stabilized with mixture of
LAPB and NPs, fine ~70 MUm bubbles and high viscosities on the order of 100 cP
at>0.90 internal phase fraction were stabilized for hours to days. The surfactant
reduces interfacial tension, and thus facilitates bubble generation and decreases
the capillary pressure to reduce the drainage rate of the lamella. The LAPB,
which is in the cationic protonated form, also attracts anionic NPs (and anionic
HPAM in systems containing polymer) to the interface. The adsorbed NPs at the
interface are shown to slow down Ostwald ripening (with or without polymer added)
and increase foam stability. In systems with added HPAM, the increase in the bulk
and surface viscosity of the aqueous phase further decreases the lamella drainage
rate and inhibits coalescence of foams. Thus, the added polymer increases the
foam viscosity by threefold. Scaling law analysis shows the viscosity of 0.90
volume fraction foams is inversely proportional to the bubble size.
PMID- 26414422
TI - Maghemite nanosorbcats for methylene blue adsorption and subsequent catalytic
thermo-oxidative decomposition: Computational modeling and thermodynamics
studies.
AB - In this study methylene blue (MB) has been investigated for its adsorption and
subsequent catalytic thermo-oxidative decomposition on surface of maghemite
(gamma-Fe2O3) nanoparticles. The experimental adsorption isotherm fit well to the
Freundlich model, indicating multi-sites adsorption. Computational modeling of
the interaction between the MB molecule and gamma-Fe2O3 nanoparticle surface was
carried out to get more insights into its adsorption behavior. Adsorption
energies of MB molecules on the surface indicated that there are different
adsorption sites on the surface of gamma-Fe2O3 confirming the findings regarding
the adsorption isotherm. The catalytic activity of the gamma-Fe2O3 nanoparticles
toward MB thermo-oxidative decomposition has been confirmed by subjecting the
adsorbed MB to a thermo oxidation process up to 600 degrees C in a
thermogravimetric analyzer. The experimental results showed a catalytic activity
for post adsorption oxidation. The oxidation kinetics were studied using the
Ozawa-Flyn-Wall (OFW) corrected method. The most probable mechanism functions
were fifth and third orders for virgin MB and MB adsorbed onto gamma-Fe2O3
nanoparticles, respectively. Moreover, the results of thermodynamic transition
state parameters, namely changes in Gibbs free energy of activation (DeltaG(?)),
enthalpy of activation (DeltaH(?)), and entropy of activation (DeltaS(?)),
emphasized the catalytic activity of gamma-Fe2O3 nanoparticles toward MB
oxidation.
PMID- 26414423
TI - A confocal microscopy study of micron-sized poly(N-isopropylacrylamide) microgel
particles at the oil-water interface and anisotopic flattening of highly swollen
microgel.
AB - HYPOTHESIS: Responsive poly(N-isopropylacrylamide) microgel (PNIPAM microgel)
stabilized Pickering emulsions were investigated in this study. A recent
theoretical study of other researchers has suggested that large soft particles at
the oil/water interface are less deformable than their small counterparts.
Therefore, we expected that our micron-sized microgel particles might not
significantly deform at the oil/water interface. EXPERIMENTS: We applied confocal
laser scanning microscopy (CLSM) to examine the structure of soft PNIPAM-based
microgel particles at the decane-water interface in a microgel-stabilized
emulsion. Using micron-sized microgel particles with better labelling techniques,
we could compensate the weakness in resolution of using CLSM. Seven PNIPAM-based
microgel samples with various softness values and morphologies were examined at
different pH values. FINDINGS: Our results demonstrate that the deformation of
ordinary micron-sized microgel samples was not significant if they were not in
the pH-swollen state. Nevertheless, the soft, pH-swollen microgel particles
exhibited anisotropic deformation at the decane-water interface. Such flattening
was not reported in previous studies. The studies of microgel particles at the
oil-water interface with different imaging techniques and their comparison are
valuable to help to elucidate the particles' roles in stabilizing the Pickering
emulsions.
PMID- 26414424
TI - Trypsin and trypsin inhibitor bind PAMAM nanoparticles: Effect of hydrophobicity
on protein-polymer conjugation.
AB - Protein-polymer conjugates are widely used in therapeutic drug delivery. We
report the bindings of trypsin (Try) and trypsin inhibitor (Tryi) with
polyamidoamine (PAMAM-G4) dendrimer at physiological conditions, using
thermodynamic analysis, UV-Visible and Fourier transform infrared (FTIR)
spectroscopic methods. Thermodynamic parameters DeltaS, DeltaH and DeltaG showed
protein-PAMAM bindings occur via H-bonding and van der Waals contacts with
trypsin inhibitor forming more stable conjugate than trypsin. PAMAM complexation
induces more perturbations of trypsin inhibitor structure than trypsin with
reduction of protein alpha-helix and major changes of beta-structures. The
negative value of DeltaG indicates spontaneous protein-polymer conjugation at
room temperature.
PMID- 26414425
TI - Application of least squares support vector regression and linear multiple
regression for modeling removal of methyl orange onto tin oxide nanoparticles
loaded on activated carbon and activated carbon prepared from Pistacia atlantica
wood.
AB - Two novel and eco friendly adsorbents namely tin oxide nanoparticles loaded on
activated carbon (SnO2-NP-AC) and activated carbon prepared from wood tree
Pistacia atlantica (AC-PAW) were used for the rapid removal and fast adsorption
of methyl orange (MO) from the aqueous phase. The dependency of MO removal with
various adsorption influential parameters was well modeled and optimized using
multiple linear regressions (MLR) and least squares support vector regression
(LSSVR). The optimal parameters for the LSSVR model were found based on gamma
value of 0.76 and sigma(2) of 0.15. For testing the data set, the mean square
error (MSE) values of 0.0010 and the coefficient of determination (R(2)) values
of 0.976 were obtained for LSSVR model, and the MSE value of 0.0037 and the R(2)
value of 0.897 were obtained for the MLR model. The adsorption equilibrium and
kinetic data was found to be well fitted and in good agreement with Langmuir
isotherm model and second-order equation and intra-particle diffusion models
respectively. The small amount of the proposed SnO2-NP-AC and AC-PAW (0.015 g and
0.08 g) is applicable for successful rapid removal of methyl orange (>95%). The
maximum adsorption capacity for SnO2-NP-AC and AC-PAW was 250 mg g(-1) and 125 mg
g(-1) respectively.
PMID- 26414426
TI - Wettability alteration of oil-wet carbonate by silica nanofluid.
AB - Changing oil-wet surfaces toward higher water wettability is of key importance in
subsurface engineering applications. This includes petroleum recovery from
fractured limestone reservoirs, which are typically mixed or oil-wet, resulting
in poor productivity as conventional waterflooding techniques are inefficient. A
wettability change toward more water-wet would significantly improve oil
displacement efficiency, and thus productivity. Another area where such a
wettability shift would be highly beneficial is carbon geo-sequestration, where
compressed CO2 is pumped underground for storage. It has recently been identified
that more water-wet formations can store more CO2. We thus examined how silica
based nanofluids can induce such a wettability shift on oil-wet and mixed-wet
calcite substrates. We found that silica nanoparticles have an ability to alter
the wettability of such calcite surfaces. Nanoparticle concentration and brine
salinity had a significant effect on the wettability alteration efficiency, and
an optimum salinity was identified, analogous to that one found for surfactant
formulations. Mechanistically, most nanoparticles irreversibly adhered to the oil
wet calcite surface (as substantiated by SEM-EDS and AFM measurements). We
conclude that such nanofluid formulations can be very effective as enhanced
hydrocarbon recovery agents and can potentially be used for improving the
efficiency of CO2 geo-storage.
PMID- 26414427
TI - An Optimized Glutamate Receptor Photoswitch with Sensitized Azobenzene
Isomerization.
AB - A new azobenzene-based photoswitch, 2, has been designed to enable optical
control of ionotropic glutamate receptors in neurons via sensitized two-photon
excitation with NIR light. In order to develop an efficient and versatile
synthetic route for this molecule, a modular strategy is described which relies
on the use of a new linear fully protected glutamate derivative stable in basic
media. The resulting compound undergoes one-photon trans-cis photoisomerization
via two different mechanisms: direct excitation of its azoaromatic unit and
irradiation of the pyrene sensitizer, a well-known two-photon sensitive
chromophore. Moreover, 2 presents large thermal stability of its cis isomer, in
contrast to other two-photon responsive switches relying on the intrinsic
nonlinear optical properties of push-pull substituted azobenzenes. As a result,
the molecular system developed herein is a very promising candidate for evoking
large photoinduced biological responses during the multiphoton operation of
neuronal glutamate receptors with NIR light, which require accumulation of the
protein-bound cis state of the switch upon repeated illumination.
PMID- 26414428
TI - Fast Fabrication of Flexible Functional Circuits Based on Liquid Metal Dual-Trans
Printing.
AB - A dual-trans method to print the first functional liquid-metal circuit layout on
poly(vinyl chloride) film, and then transfer it into a poly(dimethylsiloxane)
substrate through freeze phase transition processing for the fabrication of a
flexible electronic device. A programmable soft electronic band and a temperature
sensing module wirelessly communicate with a mobile phone, demonstrating the
efficiency and capability of the method.
PMID- 26414429
TI - Risk Prioritization Tool to Identify the Public Health Risks of Wildlife Trade:
The Case of Rodents from Latin America.
AB - Wildlife trade (both formal and informal) is a potential driver of disease
introduction and emergence. Legislative proposals aim to prevent these risks by
banning wildlife imports, and creating 'white lists' of species that are cleared
for importation. These approaches pose economic harm to the pet industry, and
place substantial burden on importers and/or federal agencies to provide proof of
low risk for importation of individual species. As a feasibility study, a risk
prioritization tool was developed to rank the pathogens found in rodent species
imported from Latin America into the United States with the highest risk of
zoonotic consequence in the United States. Four formally traded species and 16
zoonotic pathogens were identified. Risk scores were based on the likelihood of
pathogen release and human exposure, and the severity of the disease
(consequences). Based on the methodology applied, three pathogens (Mycobacterium
microti, Giardia spp. and Francisella tularensis) in one species (Cavia
porcellus) were ranked as highest concern. The goal of this study was to present
a methodological approach by which preliminary management resources can be
allocated to the identified high-concern pathogen-species combinations when
warranted. This tool can be expanded to other taxa and geographic locations to
inform policy surrounding the wildlife trade.
PMID- 26414431
TI - Rhodium(III)-Catalyzed C-H Activation/Alkyne Annulation by Weak Coordination of
Peresters with O-O Bond as an Internal Oxidant.
AB - A redox-economic strategy has been developed, involved in an efficient Rh(III)
catalyzed oxidative C-H activation and alkyne annulation with perester as the
oxidizing directing group. In this process, the cleavage of an oxidizing O-O bond
as an internal oxidant is described for the first time. This reaction could be
carried out under mild conditions and exhibits excellent regioselectivity and
wide functional groups tolerance.
PMID- 26414430
TI - High Prevalence of HIV Low Abundance Drug-Resistant Variants in a Treatment-Naive
Population in North Rift Kenya.
AB - The advent of antiretroviral treatment (ART) has resulted in a dramatic reduction
in AIDS-related morbidity and mortality. However, the emergence and spread of
antiretroviral drug resistance (DR) threaten to negatively impact treatment
regimens and compromise efforts to control the epidemic. It is recommended that
surveillance of drug resistance occur in conjunction with scale-up efforts to
ensure that appropriate first-line therapy is offered relative to the resistance
that exists. However, standard resistance testing methods used in Sub-Saharan
Africa rely on techniques that do not include low abundance DR variants (LADRVs)
that have been documented to contribute to treatment failure. The use of next
generation sequencing (NGS) has been shown to be more sensitive to LADRVS. We
have carried out a preliminary investigation using NGS to determine the
prevalence of LDRVS among a drug-naive population in North Rift Kenya.
Antiretroviral-naive patients attending a care clinic in North Rift Kenya were
requested to provide and with consent provided blood samples for DR analysis. DNA
was extracted and amplified and nested PCR was conducted on the pol RT region
using primers tagged with multiplex identifiers (MID). Resulting PCR amplicons
were purified, quantified, and pyrosequenced using a GS FLX Titanium
PicoTiterPlate (Roche). Valid pyrosequencing reads were aligned with HXB-2 and
the frequency and distribution of nucleotide and amino acid changes were
determined using an in-house Perl script. DR mutations were identified using the
IAS-USA HIV DR mutation database. Sixty samples were successfully sequenced of
which 26 were subtype A, 9 were subtype D, 2 were subtype C, and the remaining
were recombinants. Forty-six (76.6%) had at least one drug resistance mutation,
with 25 (41.6%) indicated as major and the remaining 21 (35%) indicated as minor.
The most prevalent mutation was NRTI position K219Q/R (11/46, 24%) followed by
NRTI M184V (5/46, 11%) and NNRTI K103N (4/46, 9%). Our use of NGS technology
revealed a high prevalence of LADRVs among drug-naive populations in Kenya, a
region with predominantly non-B subtypes. The impact of these mutations on the
clinical outcome of ART can be ascertained only through long-term follow-up.
PMID- 26414432
TI - Does educational intervention affect resident competence in sonographic cervical
length measurement?
AB - OBJECTIVE: To determine if a structured teaching module improves resident
competency in transvaginal sonographic cervical length measurements. METHODS:
This was a prospective cohort study involving obstetrics and gynecology residents
at a single institution. Residents collected 10 transvaginal cervical images from
patients with threatened preterm labor presenting to Labor and Delivery. After
initial image acquisition, residents participated in a lecture-based teaching
module involving a pre- and post-intervention assessment. Following the didactic
session, they collected 10 additional images. All the images were scored
independently by two Maternal-Fetal Medicine attending physicians based on the
quality and accuracy of the measured cervical length. Pre-and post- intervention
test results were compared, as well as pre- and post- intervention image scores.
Parametric and nonparametric tests were used as appropriate with p < 0.05
considered significant. RESULTS: Ninety-three percent of the residents (14/15)
improved their scores from pre-test to post-test or maintained an already perfect
score (p < 0.01). Improvement was most significant with the junior residents.
Seventy-nine percent of the residents (11/14) improved their cervical image
scores after the educational session. Mean score for total residents was 73.7 +
12.6 pre-intervention and 90.2 + 9.9 post-intervention (p < 0.01) out of a total
of 120. CONCLUSIONS: There is an improvement in the competence of resident
measured cervical lengths via transvaginal ultrasound when a structured
educational module is implemented for resident education.
PMID- 26414433
TI - Post-Inpatient Brain Injury Rehabilitation Outcomes: Report from the National
OutcomeInfo Database.
AB - This study examined outcomes for intensive residential and outpatient/community
based post-inpatient brain injury rehabilitation (PBIR) programs compared with
supported living programs. The goal of supported living programs was stable
functioning (no change). Data were obtained for a large cohort of adults with
acquired brain injury (ABI) from the OutcomeInfo national database, a web-based
database system developed through National Institutes of Health (NIH) Small
Business Technology Transfer (STTR) funding for monitoring progress and outcomes
in PBIR programs primarily with the Mayo-Portland Adaptability Inventory (MPAI
4). Rasch-derived MPAI-4 measures for cases from 2008 to 2014 from 9 provider
organizations offering programs in 23 facilities throughout the United States
were examined. Controlling for age at injury, time in program, and time since
injury on admission (chronicity), both intensive residential (n = 205) and
outpatient/community-based (n = 2781) programs resulted in significant
(approximately 1 standard deviation [SD]) functional improvement on the MPAI-4
Total Score compared with supported living (n = 101) programs (F = 18.184, p <
0.001). Intensive outpatient/community-based programs showed greater improvements
on MPAI-4 Ability (F = 14.135, p < 0.001), Adjustment (F = 12.939, p < 0.001),
and Participation (F = 16.679, p < 0.001) indices than supported living programs;
whereas, intensive residential programs showed improvement primarily in
Adjustment and Participation. Age at injury and time in program had small effects
on outcome; the effect of chronicity was small to moderate. Examination of more
chronic cases (>1 year post-injury) showed significant, but smaller
(approximately 0.5 SD) change on the MPAI-4 relative to supported living programs
(F = 17.562, p < 0.001). Results indicate that intensive residential and
outpatient/community-based PIBR programs result in substantial positive
functional changes moderated by chronicity.
PMID- 26414434
TI - Canagliflozin treatment of Hispanic and non-Hispanic patients with type 2
diabetes in a US managed care setting.
AB - BACKGROUND: Hispanic/Latino (H/L) ethnicity is associated with higher prevalence
of type 2 diabetes mellitus (T2DM) and more complications and comorbidities. Few
studies of antihyperglycemic agents (AHAs) have compared H/L with non-H/L
patients. Randomized controlled trials and observational studies have shown
canagliflozin (CANA) is effective at lowering hemoglobin A1C (A1C). OBJECTIVE: To
describe characteristics and compare glycemic control between H/L and non-H/L
patients with T2DM filling their first prescription for CANA. METHODS: This
retrospective cohort study examined healthcare claims for diabetic patients who
filled >=1 prescription for CANA between 1 April 2013 and 31 October 2013. We
captured available demographic data; ethnicity was imputed as previously
published. Clinical data included the Diabetes Complications Severity Index
(DCSI), A1C values, and claims for any AHA, with 6 months of follow-up. RESULTS:
Our sample included 438 (11.4%) H/L individuals and 3408 (88.6%) non-H/L
individuals; each cohort had 43% females. The H/L patients were younger (53 vs.
56 years, p < 0.001) with higher mean baseline A1C (8.9% vs. 8.5%, respectively;
p = 0.028) compared to non-H/L patients. Mean DCSI was similar (H/L 0.92 vs. non
H/L 0.84, p = 0.289) between cohorts. More H/L patients (25%) were taking >=3
AHAs at the first CANA prescription fill (vs. 21% for non-H/L; p = 0.044), most
commonly metformin, followed by sulfonylureas, dipeptidyl peptidase-4 inhibitors,
and basal insulin. Among patients with >=2 fills for CANA, mean adherence
(proportion of days covered) was slightly lower for H/L than non-H/L patients
(0.77 vs. 0.80, p = 0.003). From their respective baseline A1C values, reduction
in A1C was significantly greater for H/L than non-H/L patients (1.1% vs. 0.8%; p
= 0.043). CONCLUSION: Compared with non-H/L patients, our H/L patients were
younger and had higher mean baseline A1C. Significant improvement in glycemic
control was observed for both cohorts, with greater improvement for H/L patients.
Additional research is warranted, including longer follow-up and adjusting for
possible confounding factors.
PMID- 26414435
TI - Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in
sickle cell anemia: A Phase III international randomized clinical trial.
AB - Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD)
ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited
available clinical data, the current standard of care for conditional TCD
velocities is observation. The efficacy of hydroxyurea in preventing conversion
from conditional to abnormal TCD (>=200 cm/sec), which confers a higher stroke
risk, has not been studied prospectively in a randomized trial. Sparing
Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart,
Lung, and Blood Institute-funded Phase III multicenter international clinical
trial comparing alternative therapy (hydroxyurea) to standard care (observation)
to prevent conversion from conditional to abnormal TCD velocity in children with
SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS
(36), HbSbeta(0) -thalassemia (1), and HbSD (1), median age = 5.4 years (range,
2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE
was terminated early. In an intention-to-treat analysis, the cumulative incidence
of abnormal conversion was 9% (95% CI = 0-35%) in the hydroxyurea arm and 47%
(95% CI = 6-81%) in observation arm at 15 months (P = 0.16). In post hoc analysis
according to treatment received, significantly fewer children on hydroxyurea
converted to abnormal TCD velocities when compared with observation (0% vs. 50%,
P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity
was observed with hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P = 0.02). No
stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in
children with SCA and conditional velocities.
PMID- 26414436
TI - Intestine-Specific Delivery of Hydrophobic Bioactives from Oxidized Starch
Microspheres with an Enhanced Stability.
AB - An intestine-specific delivery system for hydrophobic bioactives with improved
stability was developed. It consists of oxidized potato starch polymers, where
the carboxyl groups were physically cross-linked via ferric ions. The model
hydrophobic ingredients (beta-carotene) were incorporated inside the starch
microspheres via a double-emulsion method. Confocal laser scanning microscopy
images showed that beta-carotene were distributed homogeneously in the inner oil
phase of the starch microspheres. The negative value of the zeta-potential of
microspheres increased with increasing pH and decreasing ionic strength. In vitro
release experiments showed that the microspheres were stable at acidic stomach
conditions (pH < 2), whereas at neutral intestinal conditions (pH 7.0), they
rupture to release the loaded beta-carotene. The 1,1-diphenyl-2-picrylhydrazyl
radical, 2,2-diphenyl-1-(2,4,6-trinitriphenyl), scavenging activity results
suggested that microsphere-encapsulated beta-carotene had an improved activity
after thermal treatment at 80 degrees C. The storage stability of encapsulated
beta-carotene at room temperature was also enhanced. The starch microspheres
showed potential as intestine-specific carriers with an enhanced stability.
PMID- 26414437
TI - Speciation genomics and a role for the Z chromosome in the early stages of
divergence between Mexican ducks and mallards.
AB - Speciation is a continuous and dynamic process, and studying organisms during the
early stages of this process can aid in identifying speciation mechanisms. The
mallard (Anas platyrhynchos) and Mexican duck (A. [p.] diazi) are two recently
diverged taxa with a history of hybridization and controversial taxonomy. To
understand their evolutionary history, we conducted genomic scans to characterize
patterns of genetic diversity and divergence across the mitochondrial DNA (mtDNA)
control region, 3523 autosomal loci and 172 Z-linked sex chromosome loci. Between
the two taxa, Z-linked loci (PhiST = 0.088) were 5.2 times more differentiated
than autosomal DNA (PhiST = 0.017) but comparable to mtDNA (PhiST = 0.092).
This elevated Z differentiation deviated from neutral expectations inferred from
simulated data that incorporated demographic history and differences in effective
population sizes between marker types. Furthermore, 3% of Z-linked loci, compared
to <0.1% of autosomal loci, were detected as outlier loci under divergent
selection with elevated relative (PhiST ) and absolute (dXY ) estimates of
divergence. In contrast, the ratio of Z-linked and autosomal differentiation
among the seven Mexican duck sampling locations was close to 1:1 (PhiST = 0.018
for both markers). We conclude that between mallards and Mexican ducks,
divergence at autosomal markers is largely neutral, whereas greater divergence on
the Z chromosome (or some portions thereof) is likely the product of selection
that has been important in speciation. Our results contribute to a growing body
of literature indicating elevated divergence on the Z chromosome and its likely
importance in avian speciation.
PMID- 26414438
TI - Genotypic characteristics of Mycobacterium tuberculosis circulating in Xinjiang,
China.
AB - BACKGROUND: Tuberculosis (TB), a chronic infectious disease caused by
Mycobacterium tuberculosis (MTB), poses a serious threat to human health. We
investigated the genotypes of MTB in the high prevalence province Xinjiang,
China. METHODS: From March 2010 to May 2013, 381 MTB isolates from patients with
pulmonary TB were analyzed by molecular typing of 24 mycobacterial interspersed
repetitive unit-variable number tandem repeat loci and PCR detection of the
deleted regions of difference of the Beijing/W lineage and its sublineages.
RESULTS: These isolates were shown to be highly polymorphic and to be composed of
345 unique genotypes, including 30 genotype clusters consisting of 2 or 3 strains
and 315 individual genotypes. The genotype clustering rate was 17.32% and recent
transmission index was low (9.45%). The Beijing/W lineage strains accounted for
57.48% of the isolates, and this predominant family strain was further subdivided
into four sublineages: 181 (69.86%), 207 (14.61%), 105 (10.96%), and 150 (4.56%).
CONCLUSIONS: The Beijing/W lineage (especially sublineage 181) strains were
predominant and were associated with the transmissibility of TB in Xinjiang.
Based on our data, we hypothesize that the circulating MTB strains in Xinjiang
have significant genetic diversity and that the majority of the TB in Xinjiang
may be explained by non-recent transmission emerging by endogenous reactivation.
The possibility of outbreak is low, and current measures to control TB should
first focus on standardized treatment of TB patients to prevent reactivation of
latent infections.
PMID- 26414440
TI - The response of broccoli (Brassica oleracea convar. italica) varieties on foliar
application of selenium: uptake, translocation, and speciation.
AB - A model small-scale field experiment was set up to investigate selenium (Se)
uptake by four different varieties of broccoli plants, as well as the effect of
Se foliar application on the uptake of essential elements for plants calcium
(Ca), copper (Cu), iron (Fe), potassium (K), magnesium (Mg), manganese (Mn),
phosphorus (P), sulfur (S), and zinc (Zn). Foliar application of sodium selenate
(Na2SeO4) was carried out at two rates (25 and 50 g Se/ha), and an untreated
control variant was included. Analyses of individual parts of broccoli were
performed, whereby it was found that Se in the plant accumulates mainly in the
flower heads and slightly less in the leaves, stems, and roots, regardless of the
Se rate and broccoli variety. In most cases, there was a statistically
significant increase of Se content in all parts of the plant, while there was no
confirmed systematic influence of the addition of Se on the changing intake of
other monitored elements. Selenization of broccoli leads to an effective increase
in the Se content at a rate of 25 g/ha, whereas the higher rate did not result in
a substantial increase of Se content compared to the lower rate in all varieties.
Therefore, the rate of 25 g/ha can be recommended as effective to produce
broccoli with an increased Se content suitable for consumption. Moreover, Se
application resulted in an adequate increase of the main organic compounds of Se,
such as selenocystine (SeCys2), selenomethionine (SeMet), and Se
methylselenocysteine (Se-MeSeCys).
PMID- 26414439
TI - Rebuilding Brain Circuitry with Living Micro-Tissue Engineered Neural Networks.
AB - Prominent neuropathology following trauma, stroke, and various neurodegenerative
diseases includes neuronal degeneration as well as loss of long-distance axonal
connections. While cell replacement and axonal pathfinding strategies are often
explored independently, there is no strategy capable of simultaneously replacing
lost neurons and re-establishing long-distance axonal connections in the central
nervous system. Accordingly, we have created micro-tissue engineered neural
networks (micro-TENNs), which are preformed constructs consisting of long
integrated axonal tracts spanning discrete neuronal populations. These living
micro-TENNs reconstitute the architecture of long-distance axonal tracts, and
thus may serve as an effective substrate for targeted neurosurgical
reconstruction of damaged pathways in the brain. Cerebral cortical neurons or
dorsal root ganglia neurons were precisely delivered into the tubular constructs,
and properties of the hydrogel exterior and extracellular matrix internal column
(180-500 MUm diameter) were optimized for robust neuronal survival and to promote
axonal extensions across the 2.0 cm tube length. The very small diameter permits
minimally invasive delivery into the brain. In this study, preformed micro-TENNs
were stereotaxically injected into naive rats to bridge deep thalamic structures
with the cerebral cortex to assess construct survival and integration. We found
that micro-TENN neurons survived at least 1 month and maintained their long
axonal architecture along the cortical-thalamic axis. Notably, we also found
neurite penetration from micro-TENN neurons into the host cortex, with evidence
of synapse formation. These micro-TENNs represent a new strategy to facilitate
nervous system repair by recapitulating features of neural pathways to restore or
modulate damaged brain circuitry.
PMID- 26414441
TI - Fluorescent Ensemble Based on Bispyrene Fluorophore and Surfactant Assemblies:
Sensing and Discriminating Proteins in Aqueous Solution.
AB - A particular bispyrene fluorophore (1) with two pyrene moieties covalently linked
via a hydrophilic spacer was synthesized. Fluorescence measurements reveal that
the fluorescence emission of 1 could be well modulated by a cationic surfactant,
dodecyltrimethylammonium bromide (DTAB). Protein sensing studies illustrate that
the selected ensemble based on 1/DTAB assemblies exhibits ratiometric responses
to nonmetalloproteins and turn-off responses to metalloproteins, which can be
used to differentiate the two types of proteins. Moreover, negatively charged
nonmetalloproteins can be discriminated from the positively charged ones
according to the difference in ratiometric responses. Fluorescence sensing
studies with control bispyrenes indicate that the polarity of the spacer
connecting two pyrene moieties plays an important role in locating bispyrene
fluorophore in DTAB assemblies, which further influences its sensing behaviors to
noncovalent interacting proteins. This study sheds light on the influence of the
probe structure on the sensing performance of a fluorescent ensemble based on
probe and surfactant assemblies.
PMID- 26414442
TI - Hovering and forward flight of the hawkmoth Manduca sexta: trim search and 6-DOF
dynamic stability characterization.
AB - We show that the forward flight speed affects the stability characteristics of
the longitudinal and lateral dynamics of a flying hawkmoth; dynamic modal
structures of both the planes of motion are altered due to variations in the
stability derivatives. The forward flight speed u e is changed from 0.00 to 1.00
m s(-1) with an increment of 0.25 m s(-1). (The equivalent advance ratio is 0.00
to 0.38; the advance ratio is the ratio of the forward flight speed to the
average wing tip speed.) As the flight speed increases, for the longitudinal
dynamics, an unstable oscillatory mode becomes more unstable. Also, we show that
the up/down (w(b)) dynamics become more significant at a faster flight speed due
to the prominent increase in the stability derivative Z(u) (up/down force due to
the forward/backward velocity). For the lateral dynamics, the decrease in the
stability derivative L(v) (roll moment due to side slip velocity) at a faster
flight speed affects a slightly damped stable oscillatory mode, causing it to
become more stable; however, the t(half) (the time taken to reach half the
amplitude) of this slightly damped stable oscillatory mode remains relatively
long (~12T at u(e) = 1 m s(-1); T is wingbeat period) compared to the other modes
of motion, meaning that this mode represents the most vulnerable dynamics among
the lateral dynamics at all flight speeds. To obtain the stability derivatives,
trim conditions for linearization are numerically searched to find the exact trim
trajectory and wing kinematics using an algorithm that uses the gradient
information of a control effectiveness matrix and fully coupled six-degrees of
freedom nonlinear multibody equations of motion. With this algorithm, trim
conditions that consider the coupling between the dynamics and aerodynamics can
be obtained. The body and wing morphology, and the wing kinematics used in this
study are based on actual measurement data from the relevant literature. The
aerodynamic model of the flapping wings of a hawkmoth is based on the blade
element theory, and the necessary aerodynamic coefficients, including the lift,
drag and wing pitching moment, are experimentally obtained from the results of
previous work by the authors.
PMID- 26414445
TI - Ribozymes: How RNA catalyzes cyclization.
PMID- 26414443
TI - The protein activator of protein kinase R, PACT/RAX, negatively regulates protein
kinase R during mouse anterior pituitary development.
AB - The murine double-stranded RNA-binding protein termed protein kinase R (PKR)
associated protein X (RAX) and the human homolog, protein activator of PKR
(PACT), were originally characterized as activators of PKR. Mice deficient in RAX
show reproductive and developmental defects, including reduced body size,
craniofacial defects and anterior pituitary hypoplasia. As these defects are not
observed in PKR-deficient mice, the phenotype has been attributed to PKR
independent activities of RAX. Here we further investigated the involvement of
PKR in the physiological function of RAX, by generating rax(-/-) mice deficient
in PKR, or carrying a kinase-inactive mutant of PKR (K271R) or an
unphosphorylatable mutant of the PKR substrate eukaryotic translation initiation
factor 2 alpha subunit (eIF2alpha) (S51A). Ablating PKR expression rescued the
developmental and reproductive deficiencies in rax(-/-) mice. Generating rax(-/-)
mice with a kinase-inactive mutant of PKR resulted in similar rescue, confirming
that the rax(-/-) defects are PKR dependent; specifically that the kinase
activity of PKR was required for these defects. Moreover, generating rax(-/-)
mice that were heterozygous for an unphosphorylatable mutant eIF2alpha provides
partial rescue of the rax(-/-) defect, consistent with mutation of one copy of
the Eif2s1 gene. These observations were further investigated in vitro by
reducing RAX expression in anterior pituitary cells, resulting in increased PKR
activity and induction of the PKR-regulated cyclin-dependent kinase inhibitor
p21(WAF1/CIP1). These results demonstrate that PKR kinase activity is required
for onset of the rax(-/-) phenotype, implying an unexpected function for RAX as a
negative regulator of PKR in the context of postnatal anterior pituitary tissue,
and identify a critical role for the regulation of PKR activity for normal
development.
PMID- 26414444
TI - Notch-modifying xylosyltransferase structures support an SNi-like retaining
mechanism.
AB - A major question remaining in glycobiology is how a glycosyltransferase (GT) that
retains the anomeric linkage of a sugar catalyzes the reaction. Xyloside alpha
1,3-xylosyltransferase (XXYLT1) is a retaining GT that regulates Notch receptor
activation by adding xylose to the Notch extracellular domain. Here, using
natural acceptor and donor substrates and active Mus musculus XXYLT1, we report a
series of crystallographic snapshots along the reaction, including an
unprecedented natural and competent Michaelis reaction complex for retaining
enzymes. These structures strongly support the SNi-like reaction as the retaining
mechanism for XXYLT1. Unexpectedly, the epidermal growth factor-like repeat
acceptor substrate undergoes a large conformational change upon binding to the
active site, providing a structural basis for substrate specificity. Our improved
understanding of this retaining enzyme will accelerate the design of retaining GT
inhibitors that can modulate Notch activity in pathological situations in which
Notch dysregulation is known to cause cancer or developmental disorders.
PMID- 26414447
TI - The roles of CD147 in the progression of gliomas.
AB - Gliomas are characterized by their invasiveness, angiogenesis, glycolysis and
poor prognosis. Determining how to inhibit angiogenesis and glycolysis and induce
cell death in gliomas is essential to the development of an effective therapy.
CD147, a highly glycosylated transmembrane glycoprotein with two Ig-like
extracellular domains that belongs to the immunoglobulin superfamily, plays an
important role in the regulation of tumor invasiveness, angiogenesis and
glycolysis by inducing the secretion of matrix metalloproteinases and vascular
endothelial growth factor and by interacting with monocarboxylate transporters.
In this review, we first summarize the roles played by CD147 in gliomas and then
propose that CD147 may be a complementary prognostic biomarker and a possible
therapeutic target for glioma treatment.
PMID- 26414448
TI - Contact Forces between TiO2 Nanoparticles Governed by an Interplay of Adsorbed
Water Layers and Roughness.
AB - Interparticle forces govern the mechanical behavior of granular matter and direct
the hierarchical assembling of nanoparticles into supramolecular structures.
Understanding how these forces change under different ambient conditions would
directly benefit industrial-scale nanoparticle processing units such as filtering
and fluidization. Here we rationalize and quantify the contributions of
dispersion, capillary, and solvation forces between hydrophilic TiO2
nanoparticles with sub-10 nm diameter and show that the humidity dependence of
the interparticle forces is governed by a delicate interplay between the
structure of adsorbed water layers and the surface roughness. All-atom molecular
dynamics modeling supported by force-spectroscopy experiments reveals an
unexpected decrease in the contact forces at increasing humidity for nearly
spherical particles, while the forces between rough particles are insensitive to
strong humidity changes. Our results also frame the limits of applicability of
discrete solvation and continuum capillary theories in a regime where
interparticle forces are dominated by the molecular nature of surface adsorbates.
PMID- 26414446
TI - Crystal structure of the Varkud satellite ribozyme.
AB - The Varkud satellite (VS) ribozyme mediates rolling-circle replication of a
plasmid found in the Neurospora mitochondrion. We report crystal structures of
this ribozyme from Neurospora intermedia at 3.1 A resolution, which revealed an
intertwined dimer formed by an exchange of substrate helices. In each protomer,
an arrangement of three-way helical junctions organizes seven helices into a
global fold that creates a docking site for the substrate helix of the other
protomer, resulting in the formation of two active sites in trans. This mode of
RNA-RNA association resembles the process of domain swapping in proteins and has
implications for RNA regulation and evolution. Within each active site, adenine
and guanine nucleobases abut the scissile phosphate, poised to serve direct roles
in catalysis. Similarities to the active sites of the hairpin and hammerhead
ribozymes highlight the functional importance of active-site features, underscore
the ability of RNA to access functional architectures from distant regions of
sequence space, and suggest convergent evolution.
PMID- 26414449
TI - Evaluating the Effects of Metformin Use on Height in Children and Adolescents: A
Meta-analysis of Randomized Clinical Trials.
AB - IMPORTANCE: Metformin hydrochloride use is increasing in children and
adolescents. Previous meta-analyses have identified a large variability in the
effects of metformin use on body mass index changes but have not considered
height changes as a confounder, to our knowledge. OBJECTIVE: To conduct a
systematic review and meta-analysis of the effects of metformin use on height in
children and adolescents. DATA SOURCES: Computerized databases, including MEDLINE
and EMBASE, were searched up to September 9, 2014, for terms related to metformin
and childhood or adolescence. STUDY SELECTION: Randomized clinical trials
examining the effects of metformin use on height of participants younger than 19
years were considered eligible. Trials with cointerventions other than lifestyle
changes were excluded. DATA EXTRACTION AND SYNTHESIS: Height, weight, body mass
index, age, sex, metformin dosage, and study duration were independently
extracted by 2 reviewers. The weighted mean differences for changes in height,
weight, and body mass index were compared between the metformin and control
groups using random-effects models. MAIN OUTCOME AND MEASURE: Height changes.
RESULTS: Ten studies were included, with a total of 562 participants, 330 (58.7%)
of whom were female. The mean age within the studies ranged from 7.9 to 16.1
years, with a high variability in most studies. The duration of metformin
interventions lasted from 3 to 48 months. Overall, height changes were not
significantly different between the metformin and control groups. However,
stratified analyses according to the cumulative metformin dose (in milligrams per
day times the number of days of treatment) showed a greater increase in height
with metformin use in the 5 studies providing the largest cumulative metformin
doses (weighted mean difference, 1.0; 95% CI, 0.0 to 2.0 cm) but not in the 5
studies providing the lowest doses (weighted mean difference, -0.1; 95% CI, -0.7
to 1.0 cm) compared with the control group. CONCLUSIONS AND RELEVANCE:
Preliminary evidence suggests a dose-response relationship between metformin use
and increases in height in children and adolescents compared with a control
group. While an approximate 1-cm increase in height may appear small, it is
likely underestimated given that many studies were of short duration and included
older adolescents, potentially after epiphyseal growth plate closure.
PMID- 26414450
TI - Cyclosporine-inhibitable Cerebral Drug Transport Does Not Influence Clinical
Methadone Pharmacodynamics: Erratum.
AB - [This corrects the article on p. 1281 in vol. 121, issue 6, PMID: 25072223.].
PMID- 26414451
TI - Multidimensional Analysis of Magnetic Resonance Imaging Predicts Early Impairment
in Thoracic and Thoracolumbar Spinal Cord Injury.
AB - Literature examining magnetic resonance imaging (MRI) in acute spinal cord injury
(SCI) has focused on cervical SCI. Reproducible systems have been developed for
MRI-based grading; however, it is unclear how they apply to thoracic SCI. Our
hypothesis is that MRI measures will group as coherent multivariate principal
component (PC) ensembles, and that distinct PCs and individual variables will
show discriminant validity for predicting early impairment in thoracic SCI. We
undertook a retrospective cohort study of 25 patients with acute thoracic SCI who
underwent MRI on admission and had American Spinal Injury Association Impairment
Scale (AIS) assessment at hospital discharge. Imaging variables of axial grade,
sagittal grade, length of injury, thoracolumbar injury classification system
(TLICS), maximum canal compromise (MCC), and maximum spinal cord compression
(MSCC) were collected. We performed an analytical workflow to detect multivariate
PC patterns followed by explicit hypothesis testing to predict AIS at discharge.
All imaging variables loaded positively on PC1 (64.3% of variance), which was
highly related to AIS at discharge. MCC, MSCC, and TLICS also loaded positively
on PC2 (22.7% of variance), while variables concerning cord signal abnormality
loaded negatively on PC2. PC2 was highly related to the patient undergoing
surgical decompression. Variables of signal abnormality were all negatively
correlated with AIS at discharge with the highest level of correlation for axial
grade as assessed with the Brain and Spinal Injury Center (BASIC) score. A
multiple variable model identified BASIC as the only statistically significant
predictor of AIS at discharge, signifying that BASIC best captured the variance
in AIS within our study population. Our study provides evidence of convergent
validity, construct validity, and clinical predictive validity for the sampled
MRI measures of SCI when applied in acute thoracic and thoracolumbar SCI.
PMID- 26414452
TI - A TMEM16F point mutation causes an absence of canine platelet TMEM16F and
ineffective activation and death-induced phospholipid scrambling.
AB - BACKGROUND: TMEM16F is an ion channel and calcium-dependent lipid scramblase that
mediates phosphatidylserine (PS) exposure on the plasma membrane. Two disparate
disease phenotypes are associated with TMEM16F loss-of-function mutations: a rare
bleeding disorder (Scott syndrome) and skeletal malformations due to aberrant
bone mineralization in a TMEM16F knockout mouse. We therefore undertook
comparative studies of TMEM16F expression in canine Scott syndrome (CSS), an
autosomal recessive platelet defect. OBJECTIVES: To define anoctamin proteins and
scramblase response of CSS platelets and to determine whether TMEM16F is the CSS
disease gene. METHODS: CSS TMEM16F cDNA and gene were sequenced and mutation
detection was performed in CSS pedigrees. Platelet fractions from CSS dogs were
isolated for proteomic and immunologic characterization of TMEM16F. Annexin V was
used as a flow cytometric marker of induced platelet PS externalization. RESULTS:
A TMEM16F splice site mutation segregated with the CSS trait and TMEM16F protein
was undetectable in CSS platelet membranes; however, a second anoctamin, TMEM16K,
was found. Proteomic analyses revealed a network of 32 proteins that
differentially cosegregated with platelet plasma membrane TMEM16F. CSS platelets
had profoundly impaired scramblase response to pharmacologic and physiologic
agents that increase intraplatelet calcium and conditions that induce apoptotic
and necrotic cell death. CONCLUSIONS: CSS platelets represent a TMEM16F-null
mutant model that demonstrates a central role for TMEM16F in mediating platelet
PS externalization in response to activating and death signals. Platelet TMEM16F
may prove a novel drug target for modulating platelet procoagulant activity and
extending platelet life span.
PMID- 26414453
TI - Updated evidence on adjuvant treatments for gastric cancer.
AB - Gastric cancer is one of the main causes of cancer-related deaths worldwide. Even
when diagnosed as a localized disease and resected with the intent to cure,
recurrences frequently arise due to undetected or invisible micrometastases.
Importantly, several proposed multimodal strategies to eliminate micrometastases
have met some clinical success. However, while pivotal Phase III clinical trials
comparing adjuvant therapies with surgery alone have confirmed the overall
benefit of adjunctive treatments in patients with locally advanced gastric
cancer, further improvement in postoperative outcomes is required, particularly
in stage III disease. This review presents the current status of multimodal
treatment strategies, with a particular focus on unresolved issues, based on
updated literature searches and analysis of clinical trial databases.
PMID- 26414454
TI - Occult Radiographically Evident Port-Site Hernia After Robot-Assisted Urologic
Surgery: Incidence and Risk Factors.
AB - PURPOSE: Laparoscopic trocar-site hernias (TSH) are rare, with a reported
incidence of 1% or less. The incidence of occult radiographically evident hernias
has not been described after robot-assisted urologic surgery. We evaluated the
incidence and risk factors of this problem. MATERIALS AND METHODS: A single
institution retrospective review of robot-assisted urologic surgery was performed
from April 2009 to December 2012. Patients with preoperative and postoperative CT
were included for analysis. Imaging was reviewed by two radiologists and one
urologist. RESULTS: One hundred four cases were identified, including 60 partial
nephrectomy, 38 prostatectomy, and 6 cystectomy. Mean age was 58 years and mean
body mass index (BMI) was 29 kg/m(2). The cohort was 77% male. Ten total hernias
were identified by CT in 8 patients, 2 of which were clinically evident hernias.
Excluding these two hernias, occult port-site hernias were identified
radiographically in seven patients. Per-patient incidence of occult TSH was 6.7%
(7/104), and per-port incidence was 1.4% (8/564). All hernias were midline and
30% contained bowel. Eight of the 10 occurred at 12 mm sites (p = 0.0065) and 3
of the 10 occurred at extended incisions. Age, gender, BMI, smoking status,
diabetes mellitus, immunosuppressive drug therapy, ASA score, procedure, blood
loss, prior abdominal surgery, and history of hernia were not significant risk
factors. Specimen size >40 g (p = 0.024) and wound infection (p = 0.0052) were
significant risk factors. CONCLUSION: While the incidence of clinically evident
port-site hernia remains low in robot-assisted urologic surgery, the incidence of
CT-detected occult hernia was 6.7% in this series. These occurred most often in
sites extended for specimen extraction and at larger port sites. This suggests
more attention should be paid to fascial closure at these sites.
PMID- 26414455
TI - The Application of Sheet Technology in Cartilage Tissue Engineering.
AB - Cartilage tissue engineering started to act as a promising, even essential
alternative method in the process of cartilage repair and regeneration,
considering adult avascular structure has very limited self-renewal capacity of
cartilage tissue in adults and a bottle-neck existed in conventional surgical
treatment methods. Recent progressions in tissue engineering realized the
development of more feasible strategies to treat cartilage disorders. Of these
strategies, cell sheet technology has shown great clinical potentials in the
regenerative areas such as cornea and esophagus and is increasingly considered as
a potential way to reconstruct cartilage tissues for its non-use of scaffolds and
no destruction of matrix secreted by cultured cells. Acellular matrix sheet
technologies utilized in cartilage tissue engineering, with a sandwich model, can
ingeniously overcome the drawbacks that occurred in a conventional acellular
block, where cells are often blocked from migrating because of the non-nanoporous
structure. Electrospun-based sheets with nanostructures that mimic the natural
cartilage matrix offer a level of control as well as manipulation and make them
appealing and widely used in cartilage tissue engineering. In this review, we
focus on the utilization of these novel and promising sheet technologies to
construct cartilage tissues with practical and beneficial functions.
PMID- 26414456
TI - Is there enough evidence with evolocumab and alirocumab (antibodies to proprotein
convertase substilisin-kexin type, PCSK9) on cardiovascular outcomes to use them
widely? Evaluation of Sabatine MS, Giugliano RP, Wiviott SD et al. Efficacy and
safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med
2015;372:1500-1509, and Robinson JG, Farnier M, Krempf M et al. Efficacy and
safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med
2015;372:1488-99.
AB - INTRODUCTION: Statins alone often do not reduce LDL cholesterol levels
sufficiently to given maximum cardiovascular benefit. Thus, additional drugs are
required to reduce the levels of LDL cholesterol. Monoclonal antibodies to PCSK9
have recently been shown to decrease LDL cholesterol, but it is not known whether
they improve cardiovascular outcomes. AREAS COVERED: We evaluated two clinical
trials reporting cardiovascular outcomes with antibodies to PCSK9, the OSLER
extension with evolocumab, and the ODYSSEY LONG TERM trial with alirocumab.
EXPERT OPINION: In OSLER and ODYSSEY LONG TERM, there were very few
cardiovascular outcomes, but the trials do suggest that evolocumab and alirocumab
may reduce these outcomes. However, there are also some safety concerns with both
of these antibodies. Large clinical outcome trials are underway with both
evolocumab and alirocumab, which will probably clarify both the safety concerns
and any cardiovascular benefits with these antibodies. In our opinion, these
antibodies may be suitable for use in subjects with familial
hypercholesterolemia, who are uncontrolled with their present medications,
provided intensive safety and cardiovascular monitoring is being undertaken.
However, evolocumab and alirocumab should be used with caution in other subjects,
until outcome studies in higher numbers of subjects have shown acceptable safety
and cardiovascular profiles.
PMID- 26414457
TI - The A-B-C for SORting APP.
AB - This Editorial highlights a study by Hermey and colleagues in the current issue
of Journal of Neurochemistry. In their study, the authors provide novel insights
into single-nucleotide polymorphisms associated with Alzheimer's disease and
linked to the SorCS1 gene, toward a better understanding of the interaction of
sorting receptor proteins which physically interact with the amyloid-beta protein
precursor (APP). SorCS1, sortilin-related VPS10 domain-containing receptor 1;
SorLA, sortilin-related Receptor with A-type Repeats. Read the full article
'SorCS1 variants and amyloid precursor protein (APP) are co-transported in
neurons but only SorCS1c modulates anterograde APP transport' on page 60.
PMID- 26414459
TI - Reframing Depression Treatment in Heart Failure.
PMID- 26414460
TI - Work Outcome in Patients With Ankylosing Spondylitis: Results From a 12-Year
Followup of an International Study.
AB - OBJECTIVE: To understand the impact of ankylosing spondylitis (AS) on work
disability (WD) over 12 years compared with the general population, and explore
factors predicting adverse work outcome, defined as new partial WD or reduction
in working hours. METHODS: Source of data was the Outcome Assessments in
Ankylosing Spondylitis International Study, which includes patients from The
Netherlands, France, and Belgium. Standardized WD rates over time compared to the
general population were calculated using indirect standardization (Dutch patients
only). Cox survival analyses identified baseline predictors as well as time
varying factors influencing adverse work outcome over 12 years. RESULTS: Of 215
patients, 55 (26%) were full WD at baseline and 139 (65%) were at risk for
adverse work outcome during followup. When compared to the general population, WD
over 12 years continued to be increased in Dutch men (incidence rate [IR] 2.9
[95% confidence interval (95% CI) 1.2, 4.6]), but less clearly for women (IR 1.2
[95% CI -0.4, 2.9]). Within the entire sample, baseline predictors of adverse
work outcome over 12 years were residence in The Netherlands (versus France or
Belgium) (hazard ratio [HR] 3.4 [95% CI 1.4, 8.4]) and worse Bath Ankylosing
Spondylitis Functional Index (BASFI) (HR 1.2 [95% CI 1.0, 1.4]). Time-varying
predictors over 12 years were residence in The Netherlands, uveitis, and either
BASFI or Bath Ankylosing Spondylitis Disease Activity Index with age and
inflammatory bowel disease. CONCLUSION: Although WD was already prevalent at
inclusion in the cohort, a substantial proportion of patients incurred further
adverse work outcome over 12 years. In addition to country of residence, uveitis,
age, and self-reported physical function or disease activity predicted long-term
adverse work outcome.
PMID- 26414461
TI - Advanced Companion Diagnostics Facilities: Opportunity Favors the Prepared
Laboratory.
PMID- 26414462
TI - Safety Assurance Factors for Electronic Health Record Resilience (SAFER)
Guidelines.
PMID- 26414463
TI - Reed-Sternberg-Like Cells in Non-Hodgkin Lymphomas.
AB - Large atypical cells with morphologic and immunophenotypic features resembling
Reed-Sternberg cells can be seen in the background of reactive lymphadenopathies
as well as non-Hodgkin lymphomas. The presence of these cells is an important
diagnostic pitfall that must be recognized by pathologists who regularly
interpret lymph node biopsies. A thorough evaluation of the morphologic and
immunophenotypic features of these cells and the cellular milieu is crucial in
achieving the correct diagnosis. In this review, examples of lymphomas presenting
with Reed-Sternberg-like cells will be provided. Additionally, a detailed
description of the common morphologic and immunophenotypic features of these
cells, as well as strategies that can be used to distinguish them from the Reed
Sternberg cells of classical Hodgkin lymphoma, will be emphasized.
PMID- 26414464
TI - Langerhans Cell Histiocytosis: A Clinicopathologic Review and Molecular
Pathogenetic Update.
AB - Langerhans cell histiocytosis (LCH) comprises a wide spectrum of clinical
disorders that have in common a proliferation of Langerhans-type cells with
characteristic morphologic, immunophenotypic, and ultrastructural features. In
part because of the diverse clinical manifestations of LCH, there has long been
controversy over whether LCH is best considered a reactive process or a neoplasm.
Herein, we discuss the clinical and pathologic features of LCH, including recent
advances in the understanding of the molecular pathogenesis of this disease that
support its categorization as a neoplasm. We also review the implications that
these recently described molecular characteristics may have on risk
stratification and treatment of LCH.
PMID- 26414465
TI - Acute Myeloid Leukemia Genetics: Risk Stratification and Implications for
Therapy.
AB - Acute myeloid leukemia is a category of diseases with a common aggressive
clinical presentation but with a prognosis and management that is dependent upon
the underlying genetic characteristics of the neoplasm. The purpose of this brief
review is to update the practicing pathologist on the current standard of care in
the genetic evaluation of acute myeloid leukemia and to highlight future
directions in the classification, genetic assessment, and management of these
devastating diseases.
PMID- 26414466
TI - MiT Family Translocation-Associated Renal Cell Carcinoma: A Contemporary Update
With Emphasis on Morphologic, Immunophenotypic, and Molecular Mimics.
AB - Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon
subtype of renal cell carcinoma characterized by recurrent gene rearrangements
involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia
transcription factor (MiT) family, which regulates differentiation in melanocytes
and osteoclasts, and MiT family gene fusions activate unique molecular programs
that can be detected immunohistochemically. Although the overall clinical
behavior of t-RCC is variable, emerging molecular data suggest the possibility of
targeted approaches to advanced disease. Thus, distinguishing t-RCC from its
morphologic, immunophenotypic, and molecular mimics may have important clinical
implications. The differential diagnosis for t-RCC includes a variety of common
renal neoplasms, particularly those demonstrating clear cell and papillary
features; in addition, because of immunophenotypic overlap and/or shared
molecular abnormalities (ie, TFE3 gene rearrangement), a distinctive set of
nonepithelial renal tumors may also warrant consideration. Directed ancillary
testing is an essential aspect to the workup of t-RCC cases and may include a
panel of immunohistochemical stains, such as PAX8, pancytokeratins, epithelial
membrane antigen, carbonic anhydrase IX, HMB-45, and Melan-A. Dual-color, break
apart fluorescent in situ hybridization for TFE3 or TFEB gene rearrangement may
be helpful in diagnostically challenging cases or when molecular confirmation is
needed.
PMID- 26414467
TI - Intraductal Carcinoma of the Prostate: Morphologic Features, Differential
Diagnoses, Significance, and Reporting Practices.
AB - The differential diagnosis for atypical cribriform lesions of the prostate has
become increasingly complex and includes intraductal carcinoma of the prostate,
high-grade prostatic intraepithelial neoplasia, and atypical intraductal
proliferations. In this review, we summarize the morphologic and molecular
features and significance of intraductal carcinoma of the prostate. We also
summarize our institution's strategy for reporting and treatment recommendations
for intraductal carcinoma of the prostate.
PMID- 26414468
TI - Olmesartan-Associated Enteropathy: A Review of Clinical and Histologic Findings.
AB - Olmesartan is an antihypertensive medication belonging to the angiotensin II
receptor blocker class of drugs that has recently been associated with severe
enteropathy. Olmesartan-associated enteropathy is uncommon and may be difficult
to recognize because of its clinical and histologic similarities to other
clinical entities, including celiac sprue and autoimmune enteropathy. The purpose
of this article is to review the clinical and histologic findings of olmesartan
associated enteropathy that have been reported in the literature and to discuss
clinical entities to consider in the differential diagnosis of olmesartan
associated enteropathy.
PMID- 26414469
TI - Metastases to the Pancreas Encountered on Endoscopic Ultrasound-Guided, Fine
Needle Aspiration.
AB - Metastatic lesions in the pancreas are very uncommon and may be difficult to
differentiate from the more commonly encountered primary neoplasms derived from
the exocrine and endocrine pancreas because of the significant overlap in
clinical presentation, imaging, and cytologic features. Metastasis to the
pancreas may occur years after treatment of the primary neoplasm and is often not
considered on initial evaluation because of the rarity of such events. The
possibility of a metastasis to the pancreas should be entertained in patients
with any prior history of malignancy because a proper diagnosis is essential in
identifying surgical candidates, or avoiding potentially unnecessary surgery and
facilitating triage to more appropriate nonoperative therapy. Herein, we describe
intrapancreatic metastases secondary to renal cell carcinoma, melanoma, and lung
carcinoma, as documented by cytologic examination of endoscopic ultrasound-guided
fine-needle aspiration of the pancreatic masses.
PMID- 26414470
TI - Morphologic Mimics of Invasive Lobular Carcinoma.
AB - Invasive lobular carcinoma of the breast is a relatively common diagnosis.
However, other carcinomatous as well as noncarcinomatous neoplasms, either
primary or metastatic to the breast, may mimic invasive lobular carcinoma. As
treatment may differ, establishing the correct diagnosis is paramount to
providing the appropriate care for these patients. This review outlines important
mimics of invasive lobular carcinoma and the key clinicopathologic and
immunohistochemical features as well as additional studies helpful in
establishing their diagnoses.
PMID- 26414471
TI - Pulmonary Apical Cap-What's Old Is New Again.
AB - The pulmonary apical cap (PAC) is a morphologically distinct type of unilateral
or bilateral fibroelastotic scar involving the lung apices. Despite being
relatively common and having been described more than a hundred years ago, it
remains underappreciated as a unique diagnostic entity by clinicians,
radiologists, and pathologists alike. Given the centrality of modern chest
imaging in the workup of diseases of the lungs, it may be expected that the PAC
will be biopsied with increasing frequency. As such, pathologists should be
familiar with its presentation, appearance, and differential diagnosis. This
article serves as a short overview of PAC and as a practical aid in its diagnosis
for surgical pathologists.
PMID- 26414472
TI - Atypical Spitz Tumors: A Diagnostic Challenge.
AB - Spitzoid melanocytic lesions encompass a spectrum from benign Spitz nevi to
malignant spitzoid melanomas. Spitzoid melanocytic neoplasms have significant
morphologic and molecular differences from conventional melanocytic lesions, and
prediction of biologic behavior and metastatic risk may be difficult. Most
challenging is the atypical Spitz tumor, a borderline spitzoid melanocytic lesion
of uncertain malignant potential that has overlapping histologic features with
conventional Spitz nevus and spitzoid melanoma. Atypical Spitz tumors involve the
sentinel lymph nodes at a greater frequency than conventional melanoma and
frequently harbor chromosomal copy number changes, yet most cases follow an
indolent course. Herein we review the clinical, microscopic, and molecular
features of atypical Spitz tumors, including recent molecular advances, including
the potential prognostic significance of chromosomal abnormalities, such as
homozygous CDKN2A loss.
PMID- 26414473
TI - Assessing the Impact of Analytical Error on Perceived Disease Severity.
AB - CONTEXT: The perception of the severity of disease from laboratory results
assumes that the results are free of analytical error; however, analytical error
creates a spread of results into a band and thus a range of perceived disease
severity. OBJECTIVE: To assess the impact of analytical errors by calculating the
change in perceived disease severity, represented by the hazard ratio, using non
high-density lipoprotein (nonHDL) cholesterol as an example. DESIGN: We
transformed nonHDL values into ranges using the assumed total allowable errors
for total cholesterol (9%) and high-density lipoprotein cholesterol (13%). Using
a previously determined relationship between the hazard ratio and nonHDL, we
calculated a range of hazard ratios for specified nonHDL concentrations affected
by analytical error. RESULTS: Analytical error, within allowable limits, created
a band of values of nonHDL, with a width spanning 30 to 70 mg/dL (0.78-1.81
mmol/L), depending on the cholesterol and high-density lipoprotein cholesterol
concentrations. Hazard ratios ranged from 1.0 to 2.9, a 16% to 50% error.
Increased bias widens this range and decreased bias narrows it. CONCLUSIONS:
Error-transformed results produce a spread of values that straddle the various
cutoffs for nonHDL. The range of the hazard ratio obscures the meaning of
results, because the spread of ratios at different cutoffs overlap. The magnitude
of the perceived hazard ratio error exceeds that for the allowable analytical
error, and significantly impacts the perceived cardiovascular disease risk.
Evaluating the error in the perceived severity (eg, hazard ratio) provides a new
way to assess the impact of analytical error.
PMID- 26414474
TI - Underutilization of Meta-analysis in Diagnostic Pathology.
AB - CONTEXT: Underutilization of Meta-analysis No studies to our knowledge have
investigated citations and utilization of meta-analysis in diagnostic pathology
(DP). OBJECTIVE: To characterize meta-analyses in DP compared with meta-analyses
in medicine. DESIGN: We searched PubMed for meta-analyses in 12 major DP journals
without specifying years and in 4 major medicine journals in both 2006 and 2011.
We compared articles' adjusted citation ratios (ACRs), defined as an article's
citation count divided by the mean citations for the meta-analysis, review, and
original research articles published in the same journal in the same year.
RESULTS: Forty-one of 76 DP articles, 74 of 125 medicine articles in 2011, and 52
of 83 medicine articles in 2006 were qualified meta-analyses as identified by
PubMed. The ACRs of DP meta-analysis articles were higher than those of original
research articles (2.62 +/- 2.31 versus 0.92 +/- 0.84, P < .001) and similar to
those of review articles in 2006 (2.62 +/- 2.31 versus 1.95 +/- 1.59, P = .50),
but they were similar to both in 2011 (1.85 +/- 1.39 versus 0.99 +/- 1.43, P =
.11; 1.85 +/- 1.39 versus 1.12 +/- 1.43, P = .21, respectively). Diagnostic
pathology and medicine meta-analyses had similar ACRs (1.85 +/- 1.39 versus 1.57
+/- 1.35 in 2011, P = .60; and 2.62 +/- 2.31 versus 1.85 +/- 1.90 in 2006, P =
.50, respectively). However, although DP journals published fewer meta-analyses
(0.97% versus 6.66% in 2011 and 0.67% versus 4.40% in 2006, P < .001 for both),
they published more meta-analyses using both original and published data than
medicine (21.95% versus 1.59%, P < .001). They also published more meta-analyses
per year in 2011-2014 than in 2000-2010 (6.4 +/- 1.29 versus 1.36 +/- 1.03
articles per year, P < .001). CONCLUSIONS: We found underutilization of meta
analyses in DP, despite their high ACRs and recently increased utilization. More
DP meta-analyses are needed.
PMID- 26414475
TI - Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations.
AB - The majority of patients with acute promyelocytic leukemia (APL) manifest the
t(15;17)(q24.1;q21.2) translocation; however, a minor but significant proportion
of patients with APL harbor complex, cryptic, or variant translocations, which
typically involve RARA. With the exception of ZBTB16/RARA, these variants have
similar morphologic and immunophenotypic features as classic APL. Study of the
variant forms of APL not only gives insight into the pathogenesis of APL but also
allows us to understand the mechanism of retinoid therapy. It is important to
identify these cryptic and variant translocations because certain variants,
including ZBTB16/RARA and STAT5B/RARA, are resistant to treatment with all-trans
retinoic acid, arsenic trioxide, and anthracyclines.
PMID- 26414478
TI - Cavum Septi Pellucidi in Symptomatic Former Professional Football Players.
AB - Post-mortem studies reveal a high rate of cavum septi pellucidi (CSP) in chronic
traumatic encephalopathy (CTE). It remains, however, to be determined whether or
not the presence of CSP may be a potential in vivo imaging marker in populations
at high risk to develop CTE. The aim of this study was to evaluate CSP in former
professional American football players presenting with cognitive and behavioral
symptoms compared with noncontact sports athletes. Seventy-two symptomatic former
professional football players (mean age 54.53 years, standard deviation [SD]
7.97) as well as 14 former professional noncontact sports athletes (mean age
57.14 years, SD 7.35) underwent high-resolution structural 3T magnetic resonance
imaging. Two raters independently evaluated the CSP, and interrater reliability
was calculated. Within National Football League players, an association of CSP
measures with cognitive and behavioral functioning was evaluated using a
multivariate mixed effects model. The measurements of the two raters were highly
correlated (CSP length: rho = 0.98; Intraclass Correlation Coefficient [ICC]
0.99; p < 0.0001; septum length: rho = 0.93; ICC 0.96; p < 0.0001). For presence
versus absence of CSP, there was high agreement (Cohen kappa = 0.83, p < 0.0001).
A higher rate of CSP, a greater length of CSP, as well as a greater ratio of CSP
length to septum length was found in symptomatic former professional football
players compared with athlete controls. In addition, a greater length of CSP was
associated with decreased performance on a list learning task (Neuropsychological
Assessment Battery List A Immediate Recall, p = 0.04) and decreased test scores
on a measure of estimate verbal intelligence (Wide Range Achievement Test Fourth
Edition Reading Test, p = 0.02). Given the high prevalence of CSP in
neuropathologically confirmed CTE in addition to the results of this study, CSP
may serve as a potential early in vivo imaging marker to identify those at high
risk for CTE. Future research is needed to investigate the pathomechanism
underlying the development of CSP after repetitive head impacts, and its
potential association with neuropathologically confirmed CTE.
PMID- 26414479
TI - Values in Elderly People for Exhaled Nitric Oxide Study.
AB - Ageing population is constantly increasing due to rising life expectancy;
consequently, the percentage of the elderly patients with asthma is increasing,
as well. Fractional exhaled nitric oxide (FeNO) is a biomarker of lung
inflammation, and currently it is widely used in clinical practice for asthma
diagnosis and monitoring. Yet, there are no data about normal values of FeNO in
patients of more than 65 years of age with normal lung function. The aim of this
study was to establish adult FeNO reference values for subjects older than 65
years, according to the international guidelines. FeNO was measured in 303
healthy, nonsmoking adults more than 65 years of age, with normal spirometry
values measured using the online single-breath technique. The results were
analyzed by chemiluminescent detection. The FeNO levels obtained range from 5.00
to 29.9 ppb, with a mean value of 12.48 +/- 2.80 ppb. A significant association
of FeNO levels with age (p < 0.05) was observed. There was no difference in FeNO
values between men and women unlike what was observed in younger patients. FeNO
levels in healthy controls over 65 years of age are influenced by age as in
younger adults. However, there is no difference in FeNO values in male and female
seniors, in contrast with what was found in younger adults in other studies.
These data can be useful for the clinician to interpret the values of FeNO
assessed during clinical practice.
PMID- 26414480
TI - Generation, Characterization, and Multilineage Potency of Mesenchymal-Like
Progenitors Derived from Equine Induced Pluripotent Stem Cells.
AB - Multipotent mesenchymal stromal cells (MSCs) are more and more frequently used to
treat orthopedic injuries in horses. However, these cells are limited in their
expandability and differentiation capacity. Recently, the first equine-induced
pluripotent stem cell (iPSC) lines were reported by us [ 1 ]. In vitro
differentiation of iPSCs into MSC-like cells is an attractive alternative to
using MSCs derived from other sources, as a much larger quantity of patient
specific cells with broad differentiation potential could be generated. However,
the differentiation capacity of iPSCs to MSCs and the potential for use in tissue
engineering have yet to be explored. In this study, equine iPSCs were induced to
differentiate into an MSC-like population. Upon induction, the iPSCs changed
morphology toward spindle-shaped cells similar to MSCs. The ensuing iPSC-MSCs
exhibited downregulation of pluripotency-associated genes and an upregulation of
MSC-associated genes. In addition, the cells expressed the same surface markers
as MSCs derived from equine umbilical cord blood. We then assessed the
multilineage differentiation potential of iPSC-MSCs. Although chondrogenesis was
not achieved after induction with transforming growth factor-beta 3 (TGFbeta3)
and/or bone morphogenic protein 4 (BMP-4) in 3D pellet culture, mineralization
characteristic of osteogenesis and lipid droplet accumulation characteristic of
adipogenesis were observed after chemical induction. We demonstrate a protocol
for the derivation of MSC-like progenitor populations from equine iPS cells.
PMID- 26414481
TI - Did the 2009 American Recovery and Reinvestment Act affect dietary intake of low
income individuals?
AB - This paper examines the relationship between increased Supplemental Nutritional
Assistance Program (SNAP) benefits following the 2009 American Recovery and
Reinvestment Act (ARRA) and the diet quality of individuals from SNAP-eligible
compared to ineligible (those with somewhat higher income) households using data
from the 2007-2010 National Health and Nutrition Examination Survey. The ARRA
increased SNAP monthly benefits by 13.6% of the maximum allotment for a given
household size, equivalent to an increase of $24 to $144 for one-to-eight person
households respectively. In the full sample, we find that these increases in SNAP
benefits are not associated with changes in nutrient intake and diet quality.
However, among those with no more than a high school education, higher SNAP
benefits are associated with a 46% increase in the mean caloric share from sugar
sweetened beverages (SSBs) and a decrease in overall diet quality especially for
those at the lower end of the diet quality distribution, amounting to a 9%
decline at the 25th percentile.
PMID- 26414482
TI - Effects of a diet containing genetically modified rice expressing the Cry1Ab/1Ac
protein (Bacillus thuringiensis toxin) on broiler chickens.
AB - The aim of this study was to evaluate the effect of feeding Bacillus
thuringiensis (Bt) rice expressing the Cry1Ab/1Ac protein on broiler chicken. The
genetically modified (GM) Bt rice was compared with the corresponding non-GM rice
regarding performance of feeding groups, their health status, relative organ
weights, biochemical serum parameters and occurrence of Cry1Ab/1Ac gene
fragments. One hundred and eighty day-old Arbor Acres female broilers with the
same health condition were randomly allocated to the two treatments (6 replicate
cages with 15 broilers in each cage per treatment). They received diets
containing GM rice (GM group) or its parental non-GM rice (non-GM group) at 52
57% of the air-dried diet for 42 days. The results show that the transgenic rice
had a similar nutrient composition as the non-GM rice and had no adverse effects
on chicken growth, biochemical serum parameters and necropsy during the 42-day
feeding period. In birds fed the GM rice, no transgenic gene fragments were
detected in the samples of blood, liver, kidneys, spleen, jejunum, ileum,
duodenum and muscle tissue. In conclusion, the results suggest that Bt rice
expressing Cry1Ab/1Ac protein has no adverse effects on broiler chicken.
Therefore, it can be considered as safe and used as feed source for broiler
chicken.
PMID- 26414483
TI - Bandgap Tunability in Sb-Alloyed BiVO4 Quaternary Oxides as Visible Light
Absorbers for Solar Fuel Applications.
AB - The challenge of fine compositional tuning and microstructure control in complex
oxides is overcome by developing a general two-step synthetic approach. Antimony
alloyed bismuth vanadate, which is identified as a novel light absorber for solar
fuel applications, is prepared in a wide compositional range. The bandgap of this
quaternary oxide linearly decreases with the Sb content, in agreement with first
principles calculations.
PMID- 26414484
TI - Chronic Obstructive Pulmonary Disease and the Risk of Stroke. The Rotterdam
Study.
AB - RATIONALE: Worldwide, chronic obstructive pulmonary disease (COPD) and stroke are
leading causes of death. Increasing evidence suggests an association between both
diseases, either caused by an increased atherosclerosis risk in patients with
COPD or as a consequence of shared risk factors between stroke and COPD.
OBJECTIVES: To examine the associations between COPD and subtypes of stroke in
the general population and to explore the role of cardiovascular risk factors and
exacerbations on these associations. METHODS: Within the prospective population
based Rotterdam Study, we followed 13,115 participants without history of stroke
for occurrence of stroke. Follow up started in 1990 to 2008 and ended in 2012.
COPD was related to stroke using a time-dependent Cox proportional hazard model.
MEASUREMENTS AND MAIN RESULTS: COPD was diagnosed in 1,566 participants. During
126,347 person-years, 1,250 participants suffered a stroke, of which 701 were
ischemic and 107 hemorrhagic. Adjusted for age, age squared, and sex, COPD was
significantly associated with all stroke (hazard ratio [HR], 1.20; 95% confidence
interval, 1.00-1.43), ischemic stroke (HR, 1.27; 1.02-1.59), and hemorrhagic
stroke (HR, 1.70; 1.01-2.84). Adjusting for cardiovascular risk factors gave
similar effect sizes. In contrast, additional adjusting for smoking attenuated
the effect sizes: HR, 1.09 (0.91-1.31) for all stroke; HR, 1.13 (0.91-1.42) for
ischemic stroke; and HR 1.53 (0.91-2.59) for hemorrhagic stroke. After an acute
severe exacerbation, subjects with COPD had a 6.66-fold (2.42-18.20) increased
risk of stroke. CONCLUSIONS: Our cohort study demonstrated a higher risk of both
ischemic and hemorrhagic stroke in subjects with COPD and revealed the importance
of smoking as a shared risk factor.
PMID- 26414485
TI - Short Communication: Immune Activation Is Present in HIV-1-Exposed Seronegative
Individuals and Is Independent of Microbial Translocation.
AB - Analyses of immune activation in HIV-exposed seronegative individuals (HESN)
yielded discrepant results. To clarify this issue we performed an extensive
investigation of immune parameters in HESN and, in particular, we analyzed in
these individuals the possible presence of microbial translocation, the most
widely accepted reason driving immune activation in HIV-infected patients.
Results showed that immune activation, a skewing of T lymphocyte maturation, and
increased responsiveness to lipopolysaccharide (LPS) characterize the HESN
phenotype; this is not driven by alterations of the gastrointestinal barrier and
microbial translocation. The activation state seen in HESN may influence the
induction of stronger adaptive antiviral immune responses and may represent a
virus exposure-induced innate immune protective phenotype against HIV.
PMID- 26414486
TI - Do consumer voices in health-care citizens' juries matter?
AB - BACKGROUND: There is widespread agreement that the public should be engaged in
health-care decision making. One method of engagement that is gaining prominence
is the citizens' jury, which places citizens at the centre of the deliberative
process. However, little is known about how the jury process works in a health
care context. There is even less clarity about how consumer perspectives are
heard within citizens' juries and with what consequences. OBJECTIVES: This paper
focuses on what is known about the role of consumer voices within health-care
citizens' juries, how these voices are heard by jurors and whether and in what
ways the inclusion or exclusion of such voices may matter. RESULTS: Consumer
voices are not always included in health-care citizens' juries. There is a dearth
of research on the conditions under which consumer voices emerge (or not), from
which sources and why. As a result, little is known about what stories are voiced
or silenced, and how such stories are heard by jurors, with what consequences for
jurors, deliberation, decision-makers, policy and practice. DISCUSSION AND
CONCLUSION: The potential role of consumer voices in influencing deliberations
and recommendations of citizens' juries requires greater attention. Much needed
knowledge about the nuances of deliberative processes will contribute to an
assessment of the usefulness of citizens' juries as a public engagement
mechanism.
PMID- 26414487
TI - Multifetal gestations with assisted reproductive technique before the single
embryo transfer legislation: obstetric, neonatal outcomes and congenital
anomalies.
AB - OBJECTIVE: To compare perinatal, neonatal outcome and congenital anomalies of
multiple gestations conceived by means of assisted reproductive techniques with
spontaneously conceived multiples before the limitation of number of embryo
transfer. METHODS: Cases consisted of assisted reproductive technique (ART)
multifetal gestations and control group comprised of spontaneously conceived
multifetal gestations delivered in the same time period. Outcomes were perinatal,
neonatal outcome, long-term outcomes and congenital anomalies of multiple
gestations. There were 270 multifetal pregnancies for analysis, of which 137 were
achieved by ART and 133 were spontaneous in this prospective study. RESULTS:
Incidences of preeclampsia, gestational diabetes, deep vein thrombosis,
thrombocytopenia, intrahepatic cholestasis and preterm premature rupture of
membranes were similar in ART and spontaneous groups. There was no difference in
fetal malformation rates between ART and control group, but higher rates of
central nervous system malformation were observed (4 (1.5%) in control, 0 in ART
group, p = 0.04) in spontaneous group. No difference was seen in the perinatal
mortality. CONCLUSIONS: Neonatal and maternal outcomes are comparable between ART
and spontaneous multifetal gestations. Congenital fetal malformation rates
between ART and spontaneous multifetal pregnancies were similar except central
nervous system malformation that was more likely in spontaneously conceived ones.
PMID- 26414488
TI - Spiritual peace predicts 5-year mortality in congestive heart failure patients.
AB - OBJECTIVE: Spirituality is favorably related to depression, quality of life,
hospitalizations, and other important outcomes in congestive heart failure (CHF)
patients but has not been examined as a predictor of mortality risk in this
population. Given the well-known difficulties in managing CHF, we hypothesized
that spirituality would be associated with lower mortality risk, controlling for
baseline demographics, functional status, health behaviors, and religiousness.
METHOD: Participants were 191 CHF patients (64% male; M age = 68.6 years, SD =
10.1) who completed a baseline survey and were then followed for 5 years.
RESULTS: Nearly 1/3 of the sample (32%) died during the study period. Controlling
for demographics and health status, smoking more than doubled the risk of
mortality, whereas alcohol consumption was associated with slightly lower risk of
mortality. Importantly, adherence to healthy lifestyle recommendations was
associated with halved mortality risk. Although both religion and spirituality
were associated with better health behaviors at baseline in bivariate analyses, a
proportional hazard model showed that only spirituality was significantly
associated with reduced mortality risk (by 20%), controlling for demographics,
health status, and health behaviors. CONCLUSIONS: Experiencing spiritual peace,
along with adherence to a healthy lifestyle, were better predictors of mortality
risk in this sample of CHF patients than were physical health indicators such as
functional status and comorbidity. Future research might profitably examine the
efficacy of attending to spiritual issues along with standard lifestyle
interventions.
PMID- 26414489
TI - Brief Report: Association of Inflammation With Development of Erosions in
Patients With Hand Osteoarthritis: A Prospective Ultrasonography Study.
AB - OBJECTIVE: To investigate the association between features of ultrasound-detected
inflammation and development of erosive disease in patients with hand
osteoarthritis (OA) over 2.3 years of followup. METHODS: The study group
comprised 56 consecutive patients with hand OA (mean age 61 years, 86% female)
fulfilling the American College of Rheumatology criteria. Effusion, synovial
thickening, and power Doppler signal in all interphalangeal (IP) joints were
assessed with ultrasonography, using standardized methods, at baseline and
followup. Radiographs were scored at both time points for osteophytes/joint space
narrowing using the Osteoarthritis Research Society International method and for
erosive disease (E phase [erosive] and R phase [remodeling]) using the method
described by Verbruggen and Veys. Erosion development was defined as progression
from N phase (normal) to E phase or R phase. Joints that were in E phase or R
phase at baseline were excluded. Associations were analyzed using generalized
estimating equations with adjustment for age, sex, body mass index, and baseline
structural abnormalities. RESULTS: At baseline, 51 IP joints (in 18 patients) and
at followup 89 IP joints (in 26 patients) had erosions; thus, erosions developed
in 38 IP joints. Moderate/severe synovial thickening and a power Doppler signal
at baseline were associated with erosion development (adjusted odds ratio [OR]
8.8, 95% confidence interval [95% CI] 2.4-32.3 and OR 7.1, 95% CI 1.9-26.9,
respectively). Persistent inflammation was particularly associated with the
development of erosions. CONCLUSION: Ultrasound-detected features of inflammation
are associated with the development of erosions in patients with hand OA,
suggesting that inflammation plays a role in the pathogenesis of hand OA and
could be a therapeutic target.
PMID- 26414491
TI - The New Sexual Medicine-Integrating Pharmacotherapy, Sexual Therapy and Surgery
and the 4th International Consultation on Sexual Medicine.
PMID- 26414490
TI - Functional characterization of Ostreococcus tauri phototropin.
AB - Phototropins (phots) regulate a range of adaptive processes in plants that serve
to optimize photosynthetic efficiency and promote growth. Light sensing by
Arabidopsis thaliana phots is predominantly mediated by the Light, Oxygen and
Voltage sensing 2 (LOV2) flavin-binding motif located within the N-terminus of
the photoreceptor. Here we characterize the photochemical and biochemical
properties of phot from the marine picoalga Ostreococcus tauri phototropin
(Otphot) and examine its ability to replace phot-mediated function in
Arabidopsis. Photochemical properties of Otphot rely on both LOV1 and LOV2. Yet,
biochemical analysis indicates that light-dependent receptor autophosphorylation
is primarily dependent on LOV2. As found for Arabidopsis phots, Otphot associates
with the plasma membrane and partially internalizes, albeit to a limited extent,
in response to blue-light irradiation. Otphot is able to elicit a number of phot
regulated processes in Arabidopsis, including petiole positioning, leaf
expansion, stomatal opening and chloroplast accumulation movement. However,
Otphot is unable to restore phototropism and chloroplast avoidance movement.
Consistent with its lack of phototropic function in Arabidopsis, Otphot does not
associate with or trigger dephosphorylation of the phototropic signalling
component Non-Phototropic Hypocotyl 3 (NPH3). Taken together, these findings
indicate that the mechanism of action of plant and evolutionarily distant algal
phots is less well conserved than previously thought.
PMID- 26414492
TI - Rituximab with high-dose methotrexate in primary central nervous system lymphoma.
AB - The addition of rituximab (R) to chemotherapy improves outcomes in patients with
systemic B-cell non-Hodgkin lymphomas, but the impact in patients with primary
central nervous system lymphoma (PCNSL) receiving high-dose methotrexate (HDMTX)
is unknown. Patients diagnosed with PCNSL at the British Columbia Cancer Agency
(BCCA) between 2000 and 2013 were treated with >=1 cycle of HDMTX 8 g/m(2) every
2 weeks, to best response or 10 cycles. After 2006, rituximab 375 mg/m(2) was
given every 2 weeks with HDMTX for a total of 4 doses. 49 (66%) patients received
HDMTX alone and 25 (34%) HDMTX+R, with a median of 5 (range 1-10) HDMTX cycles,
and no difference between groups. The median follow-up was 5 years: 8.8 years
(range 3.15-13.5 years) HDMTX and 1.9 years (range 0.5-7 years) HDMTX+R. The 5
year PFS was 17%, with no difference between groups (HR: 0.75, 95% CI: 0.41-1.35;
P = 0.33). The 5-year OS was 38%, with no difference between the groups OS (HR:
0.73, 95% CI: 0.35-1.52; P = 0.39). In this retrospective study comparing two
subgroups of patients treated in different eras, the addition of R to HDMTX did
not appear to improve outcomes in PCNSL, possibly consistent with its known poor
CNS penetration. It is possible that with a larger sample size, longer follow-up,
or different rituximab dosing/schedule, the addition of rituximab may lead to a
statistically significant improvement in outcomes. Prospective randomized trials
currently in progress will more definitively estimate the impact of the addition
of rituximab to HDMTX-based chemotherapy for PCNSL.
PMID- 26414493
TI - Dietary exposure to aluminium from wheat flour and puffed products of residents
in Shanghai, China.
AB - A dietary survey of 3431 residents was conducted by a 24-h dietary recall method
in Shanghai, China, quarterly from September 2013 to September 2014. A total of
400 food samples were tested for aluminium concentration, including wheat flour
and puffed products from 2011 to 2013. Probabilistic analysis was used to
estimate the dietary exposure to aluminium from wheat and puffed products. The
means of dietary aluminium exposure for children (2-6 years old), juveniles (7-17
years old), adults (18-65 years old) and seniors (over 65 years old) were 1.88,
0.94, 0.44 and 0.42 mg kg(-1) body weight (bw) week(-1) respectively, with a
population average of 0.51 mg kg(-1) bw week(-1). The proportions of those who
had aluminium exposure from wheat and puffed products lower than the provisional
tolerable weekly intake (PTWI) were 77%, 90%, 97%, and 97% respectively from
children to seniors. We estimated that the proportions of people at risk would
decrease by 13%, 6%, 2% and 2% respectively under the new China National
Standards - GB 2760-2014 National Food Safety for Standards for using food
additives. The results indicated that aluminium from wheat flour and puffed
products is unlikely to cause adverse health effects in the general population in
Shanghai; however, children were at a higher risk of excess aluminium exposure.
Significant improvements in reducing the dietary exposure to aluminium are
expected in the population, especially for children after the implementation of
GB 2760-2014.
PMID- 26414494
TI - Current surgical strategies to treat fecal incontinence.
AB - Fecal incontinence is a devastating condition, vastly under-reported, and may
affect up to 18% of the population. While conservative management may be
efficacious in a large portion of patients, those who are refractory will likely
benefit from appropriate surgical intervention. There are a wide variety of
surgical approaches to fecal incontinence management, and knowledge and
experience are crucial to choosing the appropriate procedure and maximizing
functional outcome while minimizing risk. In this article, we provide a
comprehensive description of surgical options for fecal incontinence to help the
clinician identify an appropriate intervention.
PMID- 26414495
TI - Curcuminoids Modulate the PKCdelta/NADPH Oxidase/Reactive Oxygen Species
Signaling Pathway and Suppress Matrix Invasion during Monocyte-Macrophage
Differentiation.
AB - Monocyte recruitment and invasion play critical roles in the initiation and
progression of atherosclerosis. The reduction in monocyte adhesion and
infiltration is thought to exert antiatherosclerotic effects. Curcumin,
demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are the major active
components of curcuminoids and exhibit several biological activities, including
anti-inflammatory, anticarcinogenic, and hypocholesterolemic activities. The aim
of this study was to investigate the antiatherogenic effects and mechanisms of
curcuminoids during monocyte to macrophage differentiation. The results showed
that curcumin, DMC, and BDMC (20 MUM) suppressed matrix invasion from 100.0 +/-
5.0% to 24.8 +/- 1.4%, 26.6 +/- 2.9%, and 33.7 +/- 1.7%, respectively, during PMA
induced THP-1 differentiation. We found that curcuminoids significantly reduced
PMA-induced CD11b and MMP-9 expression by THP-1 cells. Production of reactive
oxygen species (ROS) induced by PMA (126.7 +/- 2.1%) was markedly attenuated by
curcumin, DMC, and BDMC to 99.5 +/- 7.8%, 87.8 +/- 8.2%, and 89.8 +/- 7.6%,
respectively, resulting in the down-regulation of CD11b and MMP-9 expression. We
demonstrated that curcuminoids inhibited NADPH oxidase through the down
regulation of NOX2 expression and the reduction of p47phox membrane
translocation. Moreover, we found involvement of PKCdelta in the PMA-induced
NOX2, CD11b, and MMP-9 mRNA expression. Curcumin, DMC, and BDMC decreased the
active form of PKCdelta protein stimulated by PMA in THP-1 cells. Overall, our
results reveal that curcuminoids suppress matrix invasion through the inhibition
of the PKCdelta/NADPH oxidase/ROS signaling pathway during monocyte-macrophage
differentiation.
PMID- 26414496
TI - Long-Term Abnormalities in the Corpus Callosum of Female Concussed Athletes.
AB - Concussion is an injury affecting millions of individuals annually that can be
associated with long-term sequelae. Recent studies have reported long-term
abnormalities in the white matter (WM) tracts of male athletes. The corpus
callosum (CC) and corticospinal tract (CST) have been shown to be particularly
vulnerable to concussion, which may be related to abnormal interhemispheric
functional connectivity and motor impairments. These anatomical pathways,
however, have not been investigated in female athletes despite the functional
significance of the CC and CST to adequate sports performance. In the present
study, 8 healthy, unconcussed female athletes (soccer, hockey) were compared with
10 female athletes (soccer, hockey, water polo) 6 months post-concussion.
Diffusion tensor imaging (DTI) of the CC and CST was conducted in a 3T magnetic
resonance imaging (MRI) scanner. DTI analysis showed no significant differences
between groups within the CST but revealed differences between groups in the CC.
The concussed group had lower mean diffusivity (t = 2.14; p = 0.048) and lower
radial diffusivity (t = 2.91; p = 0.010) in the region of the CC projecting to
the prefrontal cortex. A lower volume of WM fibers was found in the region
projecting to the premotor and supplementary motor areas (t = 2.14; p = 0.048).
Finally, lower axial diffusivity (AD) was observed in the CC area projecting
mainly to the parietal and temporal area (t = 2.23; p = 0.041). Long-term
alterations in the CC of female athletes appear to affect mostly the anterior
part of the CC projecting to the prefrontal and premotor areas. Further studies
are needed to determine whether these alterations are associated with a higher
risk of sustaining a subsequent concussive injury.
PMID- 26414497
TI - Clinical neuroscience of addiction: similarities and differences between alcohol
and other drugs.
AB - BACKGROUND: Existing pharmacological treatments for alcohol use disorder (AUD)
and other substance use disorders (SUDs) have demonstrated only modest efficacy.
Although the field has recently emphasized testing and developing new compounds
to treat SUDs, there are numerous challenges inherent to the development of novel
medications, and this is particularly true for SUDs. Thus, research to date has
tended toward the "repurposing" approach, in which medications developed to treat
other mental or physical conditions are tested as SUD treatments. Often,
potential treatments are examined across numerous drugs of abuse. Several
repurposed medications have shown promise in treating a specific SUD, but few
have shown efficacy across multiple SUDs. Examining similarities and differences
between AUD and other SUDs may shed light on these findings and offer directions
for future research. METHODS: This qualitative review discusses similarities and
differences in neural circuitry and molecular mechanism(s) across alcohol and
other substances of abuse, and examines studies of pharmacotherapies for AUD and
other SUDs. RESULTS: Substances of abuse share numerous molecular targets and
involve much of the same neural circuitry, yet compounds tested because they
putatively target common mechanisms have rarely indicated therapeutic promise for
multiple SUDs. CONCLUSIONS: The lack of treatment efficacy across SUDs may be
partially explained by limitations inherent in studying substance users, who
comprise a highly heterogeneous population. Alternatively, medications may fail
to show efficacy across multiple SUDs due to the fact that the differences
between drug mechanisms are more important than their commonalities in terms of
influencing treatment response. We suggest that exploring these differences could
support novel treatment development, aid in identifying existing medications that
may hold promise as treatments for specific SUDs, and ultimately advance
translational research efforts.
PMID- 26414499
TI - Association between Initial Fluid Choice and Subsequent In-hospital Mortality
during the Resuscitation of Adults with Septic Shock.
AB - BACKGROUND: Currently, guidelines recommend initial resuscitation with
intravenous (IV) crystalloids during severe sepsis/septic shock. Albumin is
suggested as an alternative. However, fluid mixtures are often used in practice,
and it is unclear whether the specific mixture of IV fluids used impacts
outcomes. The objective of this study is to test the hypothesis that the specific
mixture of IV fluids used during initial resuscitation, in severe sepsis, is
associated with important in-hospital outcomes. METHODS: Retrospective cohort
study includes patients with severe sepsis who were resuscitated with at least 2
l of crystalloids and vasopressors by hospital day 2, patients who had not
undergone any major surgical procedures, and patients who had a hospital length
of stay (LOS) of at least 2 days. Inverse probability weighting, propensity score
matching, and hierarchical regression methods were used for risk adjustment.
Patients were grouped into four exposure categories: recipients of isotonic
saline alone ("Sal" exclusively), saline in combination with balanced
crystalloids ("Sal + Bal"), saline in combination with colloids ("Sal + Col"), or
saline in combination with balanced crystalloids and colloids ("Sal + Bal +
Col"). In-hospital mortality was the primary outcome, and hospital LOS and costs
per day (among survivors) were secondary outcomes. RESULTS: In risk-adjusted
Inverse Probability Weighting analyses including 60,734 adults admitted to 360
intensive care units across the United States between January 2006 and December
2010, in-hospital mortality was intermediate in the Sal group (20.2%), lower in
the Sal + Bal group (17.7%, P < 0.001), higher in the Sal + Col group (24.2%, P <
0.001), and similar in the Sal + Bal + Col group (19.2%, P = 0.401). In pairwise
propensity score-matched comparisons, the administration of balanced crystalloids
by hospital day 2 was consistently associated with lower mortality, whether
colloids were used (relative risk, 0.84; 95% CI, 0.76 to 0.92) or not (relative
risk, 0.79; 95% CI, 0.70 to 0.89). The association between colloid use and in
hospital mortality was inconsistent, and survival was not uniformly affected,
whereas LOS and costs per day were uniformly increased. Results were robust in
sensitivity analyses. CONCLUSIONS: During the initial resuscitation of adults
with severe sepsis/septic shock, the types of IV fluids used may impact in
hospital mortality. When compared with the administration of isotonic saline
exclusively during resuscitation, the coadministration of balanced crystalloids
is associated with lower in-hospital mortality and no difference in LOS or costs
per day. When colloids are coadministered, LOS and costs per day are increased
without improved survival. A large randomized controlled trial evaluating
crystalloid choice is warranted. Meanwhile, the use of balanced crystalloids
seems reasonable. (Anesthesiology 2015; 123:1385-93).
PMID- 26414500
TI - Prothrombin Complex Concentrate Is Effective in Treating the Anticoagulant
Effects of Dabigatran in a Porcine Polytrauma Model.
AB - BACKGROUND: In the event of trauma, emergency reversal of anticoagulation therapy
may be required. However, no specific reversal agents are routinely available for
the direct oral anticoagulants such as dabigatran. The authors investigated four
factor prothrombin complex concentrate (PCC) for treating dabigatran-induced
anticoagulation in a porcine polytrauma model. METHODS: Dabigatran etexilate was
given orally for 3 days and intravenously on day 4 to 32 pigs. Animals were
randomized 1:1:1:1 to PCC (25, 50, or 100 U/kg) or saline. Study medication was
administered 12 min after bilateral femur fractures and blunt liver injury. The
primary endpoint was blood loss at 300 min. RESULTS: The mean plasma
concentration of dabigatran was 487 +/- 161 ng/ml after intravenous
administration. Blood loss was 3,855 +/- 258 ml in controls and 3,588 +/- 241 ml
in the PCC25 group. In the PCC50 and PCC100 groups, blood loss was significantly
lower: 1,749 +/- 47 ml and 1,692 +/- 97 ml, respectively. PCC50 and PCC100
effectively reduced dabigatran's effects on coagulation parameters, whereas
control and (to a lesser extent) PCC25 animals developed severe coagulopathy.
Sustained increases in endogenous thrombin potential occurred with PCC50 and
PCC100. CONCLUSION: Four-factor PCC (50 or 100 U/kg) is effective in reducing
blood loss in dabigatran-anticoagulated pigs, but higher doses may induce a
procoagulant state.
PMID- 26414498
TI - Neuropsychological, Metabolic, and GABAA Receptor Studies in Subjects with
Repetitive Traumatic Brain Injury.
AB - Repetitive traumatic brain injury (rTBI) occurs as a result of mild and
accumulative brain damage. A prototype of rTBI is chronic traumatic
encephalopathy (CTE), which is a degenerative disease that occurs in patients
with histories of multiple concussions or head injuries. Boxers have been the
most commonly studied patient group because they may experience thousands of
subconcussive hits over the course of a career. This study examined the
consequences of rTBI with structural brain imaging and biomolecular imaging and
investigated whether the neuropsychological features of rTBI were related to the
findings of the imaging studies. Five retired professional boxers (mean age, 46.8
+/- 3.19 years) and four age-matched controls (mean age, 48.5 +/- 3.32 years)
were studied. Cognitive-motor related functional impairment was assessed, and all
subjects underwent neuropsychological evaluation and behavioral tasks, as well as
structural brain imaging and functional-molecular imaging. In neuropsychological
tests, boxers showed deficits in delayed retrieval of visuospatial memory and
motor coordination, which had a meaningful relationship with biomolecular imaging
results indicative of neuronal injury. Morphometric abnormalities were not found
in professional boxers by structural magnetic resonance imaging (MRI). Glucose
metabolism was impaired in frontal areas associated with cognitive dysfunction,
similar to findings in Alzheimer's disease. Low binding potential (BP) of (18)F
flumazenil (FMZ) was found in the angular gyrus and temporal cortical regions,
revealing neuronal deficits. These results suggested that cognitive impairment
and motor dysfunction reflect chronic damage to neurons in professional boxers
with rTBI.
PMID- 26414501
TI - Structure and phase behaviour of diblock copolymer monolayers investigated by
means of Monte Carlo simulation.
AB - We use grand canonical Monte Carlo simulation paired with multiple histogram
reweighting, hyperparallel tempering and finite size scaling to investigate the
structure and phase behaviour of monolayers of diblock copolymers. The chain
molecules are arranged on the square lattice and we consider both fully flexible
and rod-coil polymer models. In contrast to the majority of previous studies we
assume that the interactions between the segments belonging to one of the two
subunits are weaker than the remaining segment-segment interactions. We find that
when the diblock copolymer is fully flexible, this choice of the interactions
leads to a suppression of the ordered phase, and the phase behaviour is analogous
to that of the fully flexible homopolymer model. However, when one of the
subunits is rigid, we observe the formation of a novel hairpin chessboard ordered
structure with fully stretched chains bent in the middle. The topology of the
phase diagram depends on the chain length. For shorter chains the global phase
diagram features a critical point and a triple point. For longer chains the gas
disordered liquid phase transition is suppressed and only the order-disorder
transition remains stable. The resulting phase diagram is of the swan neck type.
PMID- 26414503
TI - Application of the "Fat-but-Fit" paradigm in predicting 10-yr risk for an
atherosclerotic cardiovascular disease (ASCVD) event using the pooled cohort risk
equations among US adults.
PMID- 26414502
TI - Improving natural killer cell cancer immunotherapy.
AB - PURPOSE OF REVIEW: Natural killer (NK) cells are innate lymphoid cells
specialized to eliminate malignant cells via direct cytotoxicity and
immunoregulatory cytokine production. As such, NK cells are ideal as cellular
therapy for cancer patients, and several studies have provided proof of principle
that adoptively transferred NK cells can induce remissions in patients with
leukemia. A clear understanding of the mechanisms underlying NK cell antitumor
responses, including target cell recognition, activation status, and negative
regulatory signals will improve NK cellular therapy for cancer patients. RECENT
FINDINGS: Clinical studies have demonstrated the safety and preliminary efficacy
of NK cell adoptive transfer, especially in hematologic malignancies. Various NK
cell sources, isolation techniques, activation approaches, and ex-vivo expansion
strategies are under investigation. New approaches have been developed and are
being tested to optimize NK cell therapy, including ways to better target NK
cells to malignant cells, increase their functional competence, facilitate
expansion in patients, and limit inhibitory signals or cells. SUMMARY: NK cells
represent a promising cellular immunotherapy for the treatment of cancer. In
addition to adoptive cellular therapy, adjunct treatments that optimize NK cell
targeting and function will enhance their potency and broaden their potential use
to many cancer types.
PMID- 26414504
TI - Relationships of electrocardiographic parameters with ambulatory hypertension in
young and healthy adults.
AB - BACKGROUND: Elevated blood pressure (BP) is a leading cardiovascular risk factor
and a major determinant of left ventricular mass. Te aim of this study was to
assess electrocardiographic (ECG) changes associated with hypertension in a large
cohort of young and healthy adults. METHODS: Healthy individuals aged 25-41 years
without known cardiovascular disease were enrolled in a population based cohort
study. Resting 12-lead ECG and ambulatory 24-hour BP measurement were obtained
using validated devices. Multivariable logistic regression models were
constructed to assess the relationships between ECG parameters and daytime
hypertension, defined as systolic daytime BP>=140, diastolic BP>=90 mmHg or use
of antihypertensive treatment. RESULTS: Daytime hypertension was present among
430 of 2070 (21%) participants. Significant linear relationships were observed
between daytime hypertension with RR interval (odds ratio (OR) 95% confidence
interval (CI) 0.84 (0.78; 0.92)), R-wave amplitude in leads I and II (OR (95% CI)
2.04 (1.30; 3.19) and 1.61 (1.15; 2.24), and S-wave amplitudes in leads aVR, V1
and V2 with ORs (95% CI) of 3.28 (1.93; 5.59), 2.15 (1.51; 3.08) and 1.47 (1.18;
1.83), respectively. We also observed linear associations between daytime
hypertension and T-wave amplitudes in leads V1 (OR (95% CI) 4.83 (2.35; 9.91)),
V2 (2.18 (1.43; 3.32)), V4 (0.48 (0.29; 0.80)) and V5 (0.37 (0.19; 0.72)).
CONCLUSION: Several ECG parameters are independently associated with daytime
hypertension among young and healthy adults. This is one of the first studies to
show significant relationships between T wave amplitude and hypertension.
PMID- 26414505
TI - Organ Dose-Rate Calculations for Small Mammals at Maralinga, the Nevada Test
Site, Hanford and Fukushima: A Comparison of Ellipsoidal and Voxelized Dosimetric
Methodologies.
AB - Radiological dosimetry for nonhuman biota typically relies on calculations that
utilize the Monte Carlo simulations of simple, ellipsoidal geometries with
internal radioactivity distributed homogeneously throughout. In this manner it is
quick and easy to estimate whole-body dose rates to biota. Voxel models are
detailed anatomical phantoms that were first used for calculating radiation dose
to humans, which are now being extended to nonhuman biota dose calculations.
However, if simple ellipsoidal models provide conservative dose-rate estimates,
then the additional labor involved in creating voxel models may be unnecessary
for most scenarios. Here we show that the ellipsoidal method provides
conservative estimates of organ dose rates to small mammals. Organ dose rates
were calculated for environmental source terms from Maralinga, the Nevada Test
Site, Hanford and Fukushima using both the ellipsoidal and voxel techniques, and
in all cases the ellipsoidal method yielded more conservative dose rates by
factors of 1.2-1.4 for photons and 5.3 for beta particles. Dose rates for alpha
emitting radionuclides are identical for each method as full energy absorption in
source tissue is assumed. The voxel procedure includes contributions to dose from
organ-to-organ irradiation (shown here to comprise 2-50% of total dose from
photons and 0-93% of total dose from beta particles) that is not specifically
quantified in the ellipsoidal approach. Overall, the voxel models provide robust
dosimetry for the nonhuman mammals considered in this study, and though the level
of detail is likely extraneous to demonstrating regulatory compliance today,
voxel models may nevertheless be advantageous in resolving ongoing questions
regarding the effects of ionizing radiation on wildlife.
PMID- 26414507
TI - Accelerator-Based Biological Irradiation Facility Simulating Neutron Exposure
from an Improvised Nuclear Device.
AB - We describe here an accelerator-based neutron irradiation facility, intended to
expose blood or small animals to neutron fields mimicking those from an
improvised nuclear device at relevant distances from the epicenter. Neutrons are
generated by a mixed proton/deuteron beam on a thick beryllium target, generating
a broad spectrum of neutron energies that match those estimated for the Hiroshima
bomb at 1.5 km from ground zero. This spectrum, dominated by neutron energies
between 0.2 and 9 MeV, is significantly different from the standard reactor
fission spectrum, as the initial bomb spectrum changes when the neutrons are
transported through air. The neutron and gamma dose rates were measured using a
custom tissue-equivalent gas ionization chamber and a compensated Geiger-Mueller
dosimeter, respectively. Neutron spectra were evaluated by unfolding measurements
using a proton-recoil proportional counter and a liquid scintillator detector. As
an illustration of the potential use of this facility we present micronucleus
yields in single divided, cytokinesis-blocked human peripheral lymphocytes up to
1.5 Gy demonstrating 3- to 5-fold enhancement over equivalent X-ray doses. This
facility is currently in routine use, irradiating both mice and human blood
samples for evaluation of neutron-specific biodosimetry assays. Future studies
will focus on dose reconstruction in realistic mixed neutron/photon fields.
PMID- 26414506
TI - Evolved Cellular Mechanisms to Respond to Genotoxic Insults: Implications for
Radiation-Induced Hematologic Malignancies.
AB - Human exposure to ionizing radiation is highly associated with adverse health
effects, including reduced hematopoietic cell function and increased risk of
carcinogenesis. The hematopoietic deficits manifest across blood cell types and
persist for years after radiation exposure, suggesting a long-lived and multi
potent cellular reservoir for radiation-induced effects. As such, research has
focused on identifying both the immediate and latent hematopoietic stem cell
responses to radiation exposure. Radiation-associated effects on hematopoietic
function and malignancy development have generally been attributed to the direct
induction of mutations resulting from radiation-induced DNA damage. Other studies
have illuminated the role of cellular programs that both limit and enhance
radiation-induced tissue phenotypes and carcinogenesis. In this review, distinct
but collaborative cellular responses to genotoxic insults are highlighted, with
an emphasis on how these programmed responses impact hematopoietic cellular
fitness and competition. These radiation-induced cellular programs include
apoptosis, senescence and impaired self-renewal within the hematopoietic stem
cell (HSC) pool. In the context of sporadic DNA damage to a cell, these cellular
responses act in concert to restore tissue function and prevent selection for
adaptive oncogenic mutations. But in the contexts of whole-tissue exposure or
whole-body exposure to genotoxins, such as radiotherapy or chemotherapy, we
propose that these programs can contribute to long-lasting tissue impairment and
increased carcinogenesis.
PMID- 26414508
TI - Dose Optimization Study of AEOL 10150 as a Mitigator of Radiation-Induced Lung
Injury in CBA/J Mice.
AB - AEOL 10150 is a catalytic metalloporphyrin superoxide dismutase mimic being
developed as a medical countermeasure for radiation-induced lung injury (RILI).
The efficacy of AEOL 10150 against RILI through a reduction of oxidative stress,
hypoxia and pro-apoptotic signals has been previously reported. The goal of this
study was to determine the most effective dose of AEOL 10150 (daily subcutaneous
injections, day 1-28) in improving 180-day survival in CBA/J mice after whole
thorax lung irradiation (WTLI) to a dose of 14.6 Gy. Functional and
histopathological assessments were performed as secondary end points. Estimated
180-day survival improved from 10% in WTLI alone to 40% with WTLI-AEOL 10150 at
25 mg/kg (P = 0.065) and to 30% at 40 mg/kg (P = 0.023). No significant
improvement was seen at doses of 5 and 10 mg/kg or at doses between 25 and 40
mg/kg. AEOL 10150 treatment at 25 mg/kg lowered the respiratory function
parameter of enhanced pause (Penh) significantly, especially at week 16 and 18 (P
= 0.044 and P = 0.025, respectively) compared to vehicle and other doses.
Pulmonary edema/congestion were also significantly reduced at the time of
necropsy among mice treated with 25 and 40 mg/kg AEOL 10150 compared to WTLI
alone (P < 0.02). In conclusion, treatment with AEOL 10150 at a dose of 25
mg/kg/day for a total of 28 days starting 24 h after WTLI in CBA/J mice was found
to be the optimal dose with improvement in survival and lung function. Future
studies will be required to determine the optimal duration and therapeutic window
for drug delivery at this dose.
PMID- 26414511
TI - Slipping on pedestrian surfaces: methods for measuring and evaluating the slip
resistance.
AB - Tripping, slipping and falling accidents are among the types of accident with a
high incidence. This article describes the requirements concerning slip
resistance, as well as the state of the art of slip resistance measurement
standards in the European Community and the USA. The article also describes how
risk assessment can be performed in the field.
PMID- 26414512
TI - The Role of Decision Aids in Depression Care.
PMID- 26414509
TI - Bouvardin is a Radiation Modulator with a Novel Mechanism of Action.
AB - Protein synthesis is essential for growth, proliferation and survival of cells.
Translation factors are overexpressed in many cancers and in preclinical models,
their experimental inhibition has been shown to inhibit cancer growth.
Differential regulation of translation also occurs upon exposure to cancer
relevant stressors such as hypoxia and ionizing radiation. The failure to
regulate translation has been shown to interfere with recovery after genotoxic
stress. These findings suggest that modulation of translation, alone or in
conjunction with genotoxins, may be therapeutic in oncology. Yet, only two drugs
that directly inhibit translation are FDA-approved for oncology therapies used
today. We have previously identified the protein synthesis inhibitor, bouvardin
in a screen for small molecule enhancers of ionizing radiation in Drosophila
melanogaster . Bouvardin was independently identified in a screen for selective
inhibitors of engineered human breast cancer stem cells. Here we report the
effect of bouvardin treatment in preclinical models of head and neck cancer (HNC)
and glioma, two cancer types for which radiation therapy is the most common
treatment. Our data show that bouvardin treatment blocked translation elongation
on human ribosomes and suggest that it did so by blocking the dissociation of
elongation factor 2 from the ribosome. Bouvardin and radiation enhanced the
induction of clonogenic death in HNC and glioma cells, although by different
mechanisms. Bouvardin treatment enhanced the radiation-induced antitumor effects
in HNC tumor xenografts in mice. These data suggest that inhibition of
translation elongation, particularly in combination with radiation treatment, may
be a promising treatment option for cancer.
PMID- 26414513
TI - Is the Availability of Delayed-Release Prednisone an Important Clinical Advance?
PMID- 26414514
TI - Square-Centimeter Solution-Processed Planar CH3NH3PbI3 Perovskite Solar Cells
with Efficiency Exceeding 15.
AB - The preparation of uniform, high-crystallinity planar perovskite films with high
aspect-ratio grains over a square-inch area is demonstrated. The best power
conversion efficiency (PCE) of 16.3% (stabilized output of ~15.6%) is obtained
for a planar perovskite solar cell (PSC) with 1.2 cm2 active area, and the PCE
jumps to 18.3% (stabilized output of ~17.5%) for a PSC with a 0.12 cm2 active
area.
PMID- 26414515
TI - Nanoscopic dynamic mechanical analysis of resin-infiltrated dentine, under in
vitro chewing and bruxism events.
AB - The aim of this study was to evaluate the induced changes in mechanical behavior
and bonding capability of resin-infiltrated dentine interfaces, after application
of mechanical stimuli. Dentine surfaces were subjected to partial
demineralization through 37% phosphoric acid etching followed by the application
of an etch-and-rinse dentine adhesive, Single Bond (3M/ESPE). Bonded interfaces
were stored in simulated body fluid during 24h, and then tested or submitted to
the mechanical loading challenge. Different loading waveforms were applied: No
cycling (I), 24h cycled in sine (II) or square (III) waves, sustained loading
held for 24h (IV) or sustained loading held for 72h (V). Microtensile bond
strength (MTBS) was assessed for the different groups. Debonded dentine surfaces
were studied by field emission scanning electron microscopy (FESEM). At the resin
dentine interface, both the hybrid layer (HL) and the bottom of the hybrid layer
(BHL), and both peritubular and intertubular were evaluated using a nanoindenter
in scanning mode. The load and displacement responses were used to perform the
nano-Dynamic Mechanical analysis and to estimate the complex and storage modulus.
Dye assisted Confocal Microscopy Evaluation was used to assess sealing ability.
Load cycling increased the percentage of adhesive failures in all groups.
Specimens load cycled in held 24h attained the highest complex and storage moduli
at HL and BHL. The storage modulus was maximum in specimens load cycled in held
24h at peritubular dentine, and the lowest values were attained at intertubular
dentine. The storage modulus increased in all mechanical tests, at peritubular
dentine. An absence of micropermeability and nanoleakage after loading in sine
and square waveforms were encountered. Porosity of the resin-dentine interface
was observed when specimens were load cycled in held 72h. Areas of combined
sealing and permeability were discovered at the interface of specimens load
cycled in held 24h. Crack-bridging images appeared in samples load cycled with
sine waveform, after FESEM examination.
PMID- 26414516
TI - Modelling the degradation and elastic properties of poly(lactic-co-glycolic acid)
films and regular open-cell tissue engineering scaffolds.
AB - Scaffolding plays a critical rule in tissue engineering and an appropriate
degradation rate and sufficient mechanical integrity are required during
degradation and healing of tissue. This paper presents a computational
investigation of the molecular weight degradation and the mechanical performance
of poly(lactic-co-glycolic acid) (PLGA) films and tissue engineering scaffolds. A
reaction-diffusion model which predicts the degradation behaviour is coupled with
an entropy-based mechanical model which relates Young's modulus and the molecular
weight. The model parameters are determined based on experimental data for in
vitro degradation of a PLGA film. Microstructural models of three different
scaffold architectures are used to investigate the degradation and mechanical
behaviour of each scaffold. Although the architecture of the scaffold does not
have a significant influence on the degradation rate, it determines the initial
stiffness of the scaffold. It is revealed that the size of the scaffold strut
controls the degradation rate and the mechanical collapse. A critical length
scale due to competition between diffusion of degradation products and
autocatalytic degradation is determined to be in the range 2-100MUm. Below this
range, slower homogenous degradation occurs; however, for larger samples monomers
are trapped inside the sample and faster autocatalytic degradation occurs.
PMID- 26414519
TI - Guest editorial: Eastern Analytical Symposium 2015.
PMID- 26414521
TI - Educational editorial: interpret vibrational spectra? Why bother?
PMID- 26414517
TI - Adenoma development in familial adenomatous polyposis and MUTYH-associated
polyposis: somatic landscape and driver genes.
AB - Familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) are
inherited disorders associated with multiple colorectal adenomas that lead to a
very high risk of colorectal cancer. The somatic mutations that drive adenoma
development in these conditions have not been investigated comprehensively. In
this study we performed analysis of paired colorectal adenoma and normal tissue
DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight
MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from
each patient, and a further 63 adenomas by capillary sequencing (41 FAP, 22 MAP).
With these data we examined the profile of mutated genes, the mutational
signatures and the somatic mutation rates, observing significant diversity in the
constellations of mutated driver genes in different adenomas, and loss-of
function mutations in WTX (9%; p < 9.99e-06), a gene implicated in regulation of
the WNT pathway and p53 acetylation. These data extend our understanding of the
early events in colorectal tumourigenesis in the polyposis syndromes.
PMID- 26414522
TI - Detection of highly energetic materials on non-reflective substrates using
quantum cascade laser spectroscopy.
AB - A quantum cascade laser spectrometer was used to obtain the reflection spectra of
highly energetic materials (HEMs) deposited on nonideal, low-reflectivity
substrates, such as travel-bag fabric (polyester), cardboard, and wood. Various
deposition methods were used to prepare the standards and samples in the study.
The HEMs used were the nitroaromatic explosive 2,4,6-trinitrotoluene (TNT), the
aliphatic nitrate ester pentaerythritol tetranitrate (PETN), and the aliphatic
nitramine 1,3,5-trinitroperhydro-1,3,5-triazine (RDX). Chemometrics algorithms
were applied to analyze the recorded spectra. Partial least squares (PLS)
regression analysis was used to find the best correlation between the infrared
signals and the surface concentrations of the samples, and PLS combined with
discriminant analysis (PLS-DA) was used to discriminate, classify, and identity
similarities in the spectral datasets. Several preprocessing steps were applied
to prepare the mid-infrared spectra of HEMs deposited on the target substrates.
The results demonstrate that the infrared vibrational method described in this
study is well suited for the rapid screening analysis of HEMs on low-reflectivity
substrates when a supervised model has been previously constructed or when a
reference spectrum of the clean substrate can be acquired to be subtracted from
the HEM-substrate spectrum.
PMID- 26414523
TI - Oxygen rotational temperature determination using empirical analyses of C(3)Pi(v'
= 2) <- X(3)Sigma(v'' = 0) transitions.
AB - The spectra of molecular oxygen through C(3)Pi(v' = 2) <- X(3)Sigma(v'' = 0)
transitions have been obtained by coherent microwave Rayleigh scattering (radar)
from resonance-enhanced multiphoton ionization (REMPI). Measurements of
rotational temperatures of molecular oxygen have been demonstrated based on the
empirical analyses of the O2 spectra without the requirement of highly resolved
rotational features. Three methods, including (1) linewidth fitting, (2) linear
fitting, and (3) area fitting have been investigated for temperature measurements
within pure oxygen, ambient air, and H2-air and CH4-air flame environments. The
first two methods were applied in a moderately low temperature environment with
measurement uncertainties less than 11% and 26%, respectively. The area fitting
method covered a wider temperature range, from room temperature (~300 K) to flame
temperature (~1700 K), with minimal dependence on the fine structures of the O2
spectra. Less elaborate than Boltzmann plot analyses of ultrafine rotational
lines from congested upper rotational energy levels in O2(C(3)Pi(v' = 2)), these
empirical analyses are predictably sensitive to the thermal distribution of
molecular oxygen and have been successfully demonstrated as simple and quick
methods for remote gas-phase temperature measurement.
PMID- 26414524
TI - Laser-induced fluorescence from N2(+) ions generated by a corona discharge in
ambient air.
AB - In this work, we present the measurement of laser-induced fluorescence from N2(+)
ions via the B(2)Sigmau(+)-X(2)Sigmag(+) band system in the near-ultraviolet. The
ions were generated continuously by a plasma glow discharge in low pressure N2
and by a corona discharge in ambient air. The fluorescence decay time was found
to rapidly decrease with increasing pressure leading to an extrapolated decay
rate of ?10(10) s(-1) at atmospheric pressure. In spite of this quenching, we
were able to observe laser induced fluorescence in ambient air by means of a time
gated spectral measurement. In the process of comparing the emission signal with
that of N2 spontaneous Raman scattering, ion concentrations in ambient air of
order 10(8-)10(10) cm(-3) were determined. With moderate increases in laser power
and collection efficiency, ion concentrations of less than 10(6) cm(-3) may be
measurable, potentially enabling applications in atmospheric standoff detection
of ionizing radiation from hazardous radioactive sources.
PMID- 26414525
TI - Fourier transform infrared spectral detection of life in polar subsurface
environments and its application to Mars exploration.
AB - Cryptoendolithic lichen communities of the Dry Valleys, Antarctica, survive in an
extremely inhospitable environment, finding refuge in microscopic niches where
conditions suitable for life exist. Such "within-rock" communities may have
evolved on Mars when conditions for life on the surface deteriorated to such an
extent that they could no longer survive. Fourier transform infrared spectroscopy
of unprepared whole-rock Antarctic Beacon sandstones was used to vertically
profile molecular vibrations of fatty acids, proteins, and carboxylic acids
created by endolithic communities. Spectral biosignatures were found localized to
lichen-rich areas and were absent in crustal regions and the bulk rock substrate.
These cryptoendolithic profiles will aid similar spectroscopic investigations of
organic biosignatures during future Martian subsurface studies and will help in
the identification of similar communities in other localities across the Earth.
PMID- 26414526
TI - A prototype stationary Fourier transform spectrometer for near-infrared
absorption spectroscopy.
AB - A prototype stationary Fourier transform spectrometer (FTS) was constructed with
a fiber-coupled lithium niobate (LiNbO3) waveguide Mach-Zehnder interferometer
(MZI) for the purpose of rapid on-site spectroscopy of biological and chemical
measurands. The MZI contains push-pull electrodes for electro-optic modulation,
and its interferogram as a plot of intensity against voltage was obtained by
scanning the modulating voltage from -60 to +60 V in 50 ms. The power spectrum of
input signal was retrieved by Fourier transform processing of the interferogram
combined with the wavelength dispersion of half-wave voltage determined for the
MZI used. The prototype FTS operates in the single-mode wavelength range from
1200 to 1700 nm and allows for reproducible spectroscopy. A linear concentration
dependence of the absorbance at lambdamax = 1451 nm for water in ethanolic
solution was obtained using the prototype FTS. The near-infrared spectroscopy of
solid samples was also implemented, and the different spectra obtained with
different materials evidenced the chemical recognition capability of the
prototype FTS. To make this prototype FTS practically applicable, work on
improving its spectral resolution by increasing the maximum optical path length
difference is in progress.
PMID- 26414527
TI - Demixing of water and ethanol causes conformational redistribution and gelation
of the cationic GAG tripeptide.
AB - The cationic tripeptide GAG undergoes three conformational changes in binary
mixtures of water and ethanol. At 17 mol% of ethanol conformational sampling is
shifted from pPII towards beta-strands. A more pronounced shift in the same
direction occurs at 40 mol%. At ca. 55 mol% of ethanol and above a peptide
concentration of ca. 0.2 M the ternary peptide-water-ethanol mixture forms a
hydrogel which is comprised of unusually large crystalline like non-beta sheet
fibrils forming a sample spanning matrix.
PMID- 26414528
TI - All-passive nonreciprocal metastructure.
AB - One-way propagation of light, analogous to the directional flow of electrons in
the presence of electric potential difference, has been an important goal in the
wave-matter interaction. Breaking time-reversal symmetry in photonic flows is
faced with challenges different from those for electron flows. In recent years
several approaches and methods have been offered towards achieving this goal.
Here we investigate another systematic approach to design all-passive relatively
high-throughput metastructures that exhibit nonreciprocal properties and achieve
wave-flow isolation. Moreover, we build on those findings and propose a paradigm
for a quasi-two-dimensional metastructure that mimics the nonreciprocal property
of Faraday rotation without using any magnetic or electric biasing. We envision
that the proposed approaches may serve as a building block for all-passive time
reversal symmetry breaking with potential applications for future nonreciprocal
systems and devices.
PMID- 26414530
TI - Spiral blood flow in aorta-renal bifurcation models.
AB - The presence of a spiral arterial blood flow pattern in humans has been widely
accepted. It is believed that this spiral component of the blood flow alters
arterial haemodynamics in both positive and negative ways. The purpose of this
study was to determine the effect of spiral flow on haemodynamic changes in aorta
renal bifurcations. In this regard, a computational fluid dynamics analysis of
pulsatile blood flow was performed in two idealised models of aorta-renal
bifurcations with and without flow diverter. The results show that the spirality
effect causes a substantial variation in blood velocity distribution, while
causing only slight changes in fluid shear stress patterns. The dominant observed
effect of spiral flow is on turbulent kinetic energy and flow recirculation
zones. As spiral flow intensity increases, the rate of turbulent kinetic energy
production decreases, reducing the region of potential damage to red blood cells
and endothelial cells. Furthermore, the recirculation zones which form on the
cranial sides of the aorta and renal artery shrink in size in the presence of
spirality effect; this may lower the rate of atherosclerosis development and
progression in the aorta-renal bifurcation. These results indicate that the
spiral nature of blood flow has atheroprotective effects in renal arteries and
should be taken into consideration in analyses of the aorta and renal arteries.
PMID- 26414529
TI - The Importance of the Canonical Wnt Signaling Pathway in the Porcine Endometrial
Stromal Stem/Progenitor Cells: Implications for Regeneration.
AB - The regenerative ability of the endometrium is strongly associated with the
presence of adult stem/progenitor cells. Purposes of the present study were (1)
to establish the presence of stem/progenitor cells in porcine endometrial stroma
using a clonogenic assay and (2) to investigate whether the canonical Wnt pathway
affects the potential of stem/progenitor cells to undergo self-renewal or
differentiation. The utility of endometrial stromal clones as a model for
stem/progenitor studies was evaluated based on these cells' increased expression
of mesenchymal stem cell (MSC) marker genes, including CD29, CD73, CD90, and
CD105, compared with primary cultured cells. Small molecules were introduced to
activate (BIO) or inhibit (XAV939) the canonical Wnt pathway during stromal clone
formation. Cloning efficiency assays revealed that activation of the Wnt/beta
catenin pathway promoted formation of more differentiated small clones. Moreover,
activation of the Wnt/beta-catenin pathway decreased, whereas inhibition of the
pathway increased MSC marker expression. Additionally, we confirmed the
importance of canonical Wnt pathway stimulation in endometrial stromal cells
through observing the appropriate changes in beta-catenin cellular localization.
These data indicate that modulation of the canonical Wnt pathway effects the
process of regeneration in the porcine endometrium during the course of the
estrous cycle.
PMID- 26414531
TI - Nutrient availability and nutrient use efficiency in plants growing in the
transition zone between land and water.
AB - The transition zone between terrestrial and freshwater habitats is highly
dynamic, with large variability in environmental characteristics. Here, we
investigate how these characteristics influence the nutritional status and
performance of plant life forms inhabiting this zone. Specifically, we
hypothesised that: (i) tissue nutrient content differs among submerged,
amphibious and terrestrial species, with higher content in submerged species; and
(ii) PNUE gradually increases from submerged over amphibious to terrestrial
species, reflecting differences in the availability of N and P relative to
inorganic C across the land-water ecotone. We found that tissue nutrient content
was generally higher in submerged species and C:N and C:P ratios indicated that
content was limiting for growth for ca. 20% of plant individuals, particularly
those belonging to amphibious and terrestrial species groups. As predicted, the
PNUE increased from submerged over amphibious to terrestrial species. We suggest
that this pattern reflects that amphibious and terrestrial species allocate
proportionally more nutrients into processes of importance for photosynthesis at
saturating CO2 availability, i.e. enzymes involved in substrate regeneration,
compared to submerged species that are acclimated to lower availability of CO2 in
the aquatic environment. Our results indicate that enhanced nutrient loading may
affect relative abundance of the three species groups in the land-water ecotone
of stream ecosystems. Thus, species of amphibious and terrestrial species groups
are likely to benefit more from enhanced nutrient availability in terms of faster
growth compared to aquatic species, and that this can be detrimental to aquatic
species growing in the land-water ecotone, e.g. Ranunculus and Callitriche.
PMID- 26414532
TI - Chemotherapy and treatment algorithms for follicular lymphoma: a look at all
options.
AB - The outcome of patients with follicular lymphoma has substantially improved in
recent years, mainly due to the widespread use of the monoclonal antibody
rituximab and partially due to autologous and allogeneic transplantation, and the
introduction of new drugs and to the improvement in diagnostic accuracy. The
choice of therapy is still based on patient characteristics, extension of disease
and clinical prognostic factors. The majority of patients in need of treatment
are still treated with cytotoxic agents in combination with rituximab;
nevertheless a number of new agents, which are active in this disease, have
recently been developed. It has yet to be determined, whether they will partly or
completely replace chemotherapy in the near future. This review focuses on the
role and the choice of chemotherapy in different clinical situations of
follicular lymphoma, in a time when chemotherapy-free treatment becomes more and
more of a topic of discussion.
PMID- 26414533
TI - Pregnancy outcome in patients with ankylosing spondylitis.
AB - OBJECTIVE: The aim of this study was to evaluate pregnancy outcomes in women with
Ankylosing Spondylitis (AS), and the course of disease during pregnancy was also
assessed. METHODS: This case-control study included 60 pregnant women who
delivered in our clinic between March 2007 and 2015. Twenty of them diagnosed
with AS formed the study group and 40 women were chosen as the control group.
These patients were chosen and reviewed by their hospital records and were
evaluated retrospectively in terms of their clinical characteristics, pregnancy
complications and perinatal outcomes. The Ankylosing Spondylitis Disease Activity
Score (ASDAS), a new composite index to assess disease activity in AS, was used
in the assessment of the patients. RESULT: No adverse pregnancy outcome was noted
in pregnant patients with AS. Mean age of AS patients was significantly higher
than the controls (p = 0.037). The proportion of female fetuses was higher in
pregnancies with AS compared to pregnant patients with healthy controls (p =
0.041). Fourteen (70%) of 20 patients displayed decrement in ASDAS during
pregnancy. Course of AS was unaltered in 6 (30%) of 20 patients during pregnancy.
Otherwise, the stage of the disease during pregnancy remained unchanged in 15
(75%) of cases as postpartum exacerbation was observed in 6 (30%). The reported
symptoms of patients with AS during pregnancy were arthritis and uveitis.
CONCLUSIONS: Women with AS have a favorable pregnancy outcome, and pregnancy does
not substantially aggravate disease activity or severity in these patients.
PMID- 26414534
TI - Skin telocytes versus fibroblasts: two distinct dermal cell populations.
AB - It is already accepted that telocytes (TCs) represent a new type of interstitial
cells in human dermis. In normal skin, TCs have particular spatial relations with
different dermal structures such as blood vessels, hair follicles, arrector pili
muscles or segments of sebaceous and/or eccrine sweat glands. The distribution
and the density of TCs is affected in various skin pathological conditions.
Previous studies mentioned the particular (ultra)structure of TCs and also their
immunophenotype, miR imprint or proteome, genome or secretome features. As
fibroblast is the most common intersitital cell (also in human dermis), a
dedicated comparison between human skin TCs and fibroblasts (Fbs) was required to
be performed. In this study, using different techniques, we document several
points of difference between human dermis TCs and Fbs. By transmission electron
microscopy (TEM) and scanning electron microscopy (SEM), we demonstrated TCs with
their hallmark cellular prolongations - telopodes. Thus, we showed their
ultrastructural distinctiveness from Fbs. By RayBio Human Cytokine Antibody Array
V analyses performed on the supernatant from separately cultured TCs and Fbs, we
detected the cytokine profile of both cell types, individually. Two of 79
detected cytokines - epithelial-derived neutrophil-activating peptide 78 and
granulocyte chemotactic protein-2 - were 1.5 times higher in the supernatant of
TCs (comparing with Fbs). On the other hand, 37 cytokines were at least 1.5
higher in Fbs supernatant (comparing with TCs), and among them six cytokines -
interleukin 5, monocyte chemotactic protein-3 (MCP-3), MCP-4, macrophage
inflammatory protein-3, angiogenin, thrombopoietin - being 9.5 times higher
(results also confirmed by ELISA testing). In summary, using different
techniques, we showed that human dermal TCs and Fbs are different in terms of
ultrastructure and cytokine profile.
PMID- 26414535
TI - A brief history of the TDIF-PXY signalling module: balancing meristem identity
and differentiation during vascular development.
AB - 474 I. 474 II. 475 III. 475 IV. 477 V. 477 VI. 477 VII. 479 VIII. 481 482
References 482 SUMMARY: A significant proportion of terrestrial biomass is
constituted of xylem cells that make up woody plant tissue. Xylem is required for
water transport, and is present in the vascular tissue with a second conductive
tissue, phloem, required primarily for nutrient transport. Both xylem and phloem
are derived from cell divisions in vascular meristems known as the cambium and
procambium. One major component that influences several aspects of plant vascular
development, including cell division in the vascular meristem, vascular
organization and differentiation of vascular cell types, is a signalling module
characterized by a peptide ligand called TRACHEARY ELEMENT DIFFERENTIATION
INHIBITORY FACTOR (TDIF) and its cognate receptor, PHLOEM INTERCALATED WITH XYLEM
(PXY). In this review, we explore the literature that describes signalling
components, phytohormones and transcription factors that interact with these two
central factors, to control the varying outputs required in vascular tissues for
normal organization and elaboration of plant vascular tissue.
PMID- 26414536
TI - Associations of Circulating Soluble Tumor Necrosis Factor-alpha Receptors 1 and 2
with Interleukin-6 Levels in an Aging Cohort of Injection Drug Users with or at
High Risk for HIV Infection.
AB - Chronic inflammation marked by elevated interleukin (IL)-6, soluble tumor
necrosis factor (TNF)-alpha receptor (sTNFR)-1, and sTNFR-2 levels may play a
detrimental role in aging and HIV infection. This study aimed to evaluate the
relationships of circulating IL-6 with sTNFR-1 and sTNFR-2 levels in an aging
cohort of injection drug users (IDUs) with or at high risk for HIV infection. The
AIDS Linked to the Intravenous Experience (ALIVE) study is a community-recruited,
prospective observational study of former and current IDUs in Baltimore,
Maryland. Serum IL-6, sTNFR-1, and sTNFR-2 levels were measured using standard
ELISA. Multivariate linear regression analysis was employed, adjusting for age,
sex, HIV status, injection drug use, comorbidities, as well as HIV viral load,
CD4 T cell counts, and antiretroviral therapy where appropriate. The analysis
included 1,178 participants (316 HIV positive and 862 HIV negative). In the
adjusted model, sTNFR-1 and sTNFR-2 were individually associated with IL-6
(regression coefficient: 0.877 and 0.556, respectively, for all participants;
0.607 and 0.407 for HIV positives; and 0.999 and 0.628 for HIV negatives, all p <
0.0001). In the model combining sTNFR-1 and sTNFR-2, the associations for sTNFR-1
remained significant (0.693 for all participants, p < 0.0001; 0.417 for HIV
positives, p < 0.05; and 0.840 for HIV negatives), while those for sTNFR-2 were
no longer significant. sTNFR-1 and sTNFR-2 were positively associated with IL-6
in ALIVE participants. These findings provide initial insight into the in vivo
relationship between TNF-alpha activation and IL-6 and a basis for further
investigations into potential mechanisms underlying chronic inflammation in aging
and HIV infection.
PMID- 26414537
TI - Editorial: Unraveling Osteoarthritis Pathogenesis: New Insights Into
Preradiographic Disease and Patient Phenotypes.
PMID- 26414538
TI - "Productive and counterproductive job crafting: A daily diary study": Correction.
PMID- 26414539
TI - The role of PET scan in monitoring the progression of fibrosing mediastinitis.
AB - We present the case of a 31-year-old man who presented with acute chest pain.
Computed tomography scan showed a mediastinal mass engulfing right main-stem
bronchus and another mass surrounding descending aorta. Positron emission
tomography (PET) scan showed high mass metabolic activity. Histopathological
evaluation revealed fibroinflammatory scarring. He was diagnosed with idiopathic
fibrosing mediastinitis, started on prednisone and tamoxifen treatment, and
monitored with serial PET scans. Nine months after treatment initiation,
paraaortic abnormality had resolved and mediastinal mass had regressed.
PMID- 26414540
TI - In Response: A regulatory perspective on prioritization of emerging pollutants in
the context of the Water Framework Directive.
PMID- 26414541
TI - The Challenge: Prioritization of emerging pollutants.
PMID- 26414542
TI - In Response: The NORMAN perspectives on prioritization of emerging pollutants.
PMID- 26414543
TI - In Response: Prioritization and standard setting for pollutant mixtures in the
aquatic environment: A business consultant's perspective.
PMID- 26414544
TI - Adaptation, not acclimation, is the likely mechanism for reduced sensitivity of
some wild Hyalella populations to pyrethroid insecticides.
PMID- 26414545
TI - The authors' reply.
PMID- 26414546
TI - Corrigendum.
PMID- 26414548
TI - MicroRNA Expression and Association with Clinicopathologic Features in Papillary
Thyroid Cancer: A Systematic Review.
AB - BACKGROUND: Studies have suggested that microRNAs (miR) may be useful prognostic
markers and are associated with aggressive clinicopathologic features in
papillary thyroid cancer (PTC). This systematic review examined associations
between miRs and aggressive clinicopathologic features in PTC. METHODS: A
literature search was performed within the PubMed, Embase, Cochrane, Web of
Science, and Scopus databases for papers published prior to November 24, 2014.
The search was performed by combining the concepts "thyroid tumor" with
"microRNA" and by using "and" as the Boolean operator. Upon retrieval of
candidate studies, full-text publications were reviewed in their entirety and
selected if they examined the prognostic significance between miR expression and
established aggressive clinicopathologic features of PTC. RESULTS: Fifteen
studies from 13 unique groups that included 807 patients were reviewed. Most of
the studies were retrospective, and none included patients who had undergone
routine central lymph node dissection. Expression levels of miRs-21, -34b, -130b,
-135b, -146b, -151, -181b, -199b-5p, -221, -222, -451, -623, -1271, -2861, and
let-7e showed significant association with at least one aggressive feature, such
as large tumor size, extrathyroidal extension, multifocality, lymphovascular
invasion, lymph node metastases, distant metastasis, advanced American Joint
Cancer Committee stage, and presence of the BRAF(V600E) mutation. Herein we
summarize the literature with regard to these associations. CONCLUSION: Further
studies are needed to investigate whether miRs are independent predictors of
aggressive clinicopathologic features before it can be recommended that miR
expression levels should be incorporated into the management algorithm for
patients with PTC. A well-designed prospective study is needed to assess these
potential associations.
PMID- 26414549
TI - Effects of Multiple Ventilation Courses and Duration of Mechanical Ventilation on
Respiratory Outcomes in Extremely Low-Birth-Weight Infants.
AB - IMPORTANCE: Extubation failure is common in extremely preterm infants. The
current paucity of data on the adverse long-term respiratory outcomes associated
with reinitiation of mechanical ventilation prevents assessment of the risks and
benefits of a trial of extubation in this population. OBJECTIVE: To evaluate
whether exposure to multiple courses of mechanical ventilation increases the risk
of adverse respiratory outcomes before and after adjustment for the cumulative
duration of mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: We
performed a retrospective cohort study of extremely low-birth-weight (ELBW; birth
weight <1000 g) infants born from January 1, 2006, through December 31, 2012, who
were receiving mechanical ventilation. Analysis was conducted between November
2014 and February 2015. Data were obtained from the Alere Neonatal Database.
EXPOSURES: The primary study exposures were the cumulative duration of mechanical
ventilation and the number of ventilation courses. MAIN OUTCOMES AND MEASURES:
The primary outcome was bronchopulmonary dysplasia (BPD) among survivors.
Secondary outcomes were death, use of supplemental oxygen at discharge, and
tracheostomy. RESULTS: We identified 3343 ELBW infants, of whom 2867 (85.8%)
survived to discharge. Among the survivors, 1695 (59.1%) were diagnosed as having
BPD, 856 (29.9%) received supplemental oxygen at discharge, and 31 (1.1%)
underwent tracheostomy. Exposure to a greater number of mechanical ventilation
courses was associated with a progressive increase in the risk of BPD and use of
supplemental oxygen at discharge. Compared with a single ventilation course, the
adjusted odds ratios for BPD ranged from 1.88 (95% CI, 1.54-2.31) among infants
with 2 ventilation courses to 3.81 (95% CI, 2.88-5.04) among those with 4 or more
courses. After adjustment for the cumulative duration of mechanical ventilation,
the odds of BPD were only increased among infants exposed to 4 or more
ventilation courses (adjusted odds ratio, 1.44; 95% CI, 1.04-2.01). The number of
ventilation courses was not associated with increased risk of supplemental oxygen
use at discharge after adjustment for the length of ventilation. A greater number
of ventilation courses did not increase the risk of tracheostomy. CONCLUSIONS AND
RELEVANCE: Among ELBW infants, a longer cumulative duration of mechanical
ventilation largely accounts for the increased risk of chronic respiratory
morbidity associated with reinitiation of mechanical ventilation. These results
support attempts of extubation in ELBW infants receiving mechanical ventilation
on low ventilator settings, even when success is not guaranteed.
PMID- 26414550
TI - Saffron: Its Phytochemistry, Developmental Processes, and Biotechnological
Prospects.
AB - The present state of knowledge concerning developmental processes and the
secondary metabolism of saffron, Crocus sativus L. (Iridaceae), along with the
genes involved in these processes so far known, is reviewed. Flowers and corms
constitute the most valuable parts of saffron. Corm and flower development are
two key aspects to be studied in saffron to increase the yield and quality of the
spice, to raise its reproductive rate, and to implement new production systems.
Important knowledge about the physiology of flowering and vegetative growth has
been acquired in recent years, but there is still only limited information on
molecular mechanisms controlling these processes. Although some genes involved in
flower formation and meristem transition in other species have been isolated in
saffron, the role of these genes in this species awaits further progress. Also,
genes related with the synthesis pathway of abscisic acid and strigolactones,
growth regulators related with bud endodormancy and apical dominance
(paradormancy), have been isolated. However, the in-depth understanding of these
processes as well as of corm development is far from being achieved. By contrast,
saffron phytochemicals have been widely studied. The different flower tissues and
the corm have been proved to be an important source of phytochemicals with
pharmacological properties. The biotechnological prospects for saffron are here
reviewed on the basis of the discovery of the enzymes involved in key aspects of
saffron secondary metabolism, and we also analyze the possibility of transferring
current knowledge about flowering and vegetative propagation in model species to
the Crocus genus.
PMID- 26414551
TI - What is the impact of ethics on clinical trials?
AB - Ethics has often been ignored or evaded in clinical trials, and the conditions
under which global clinical trials are conducted make this problem likely to
persist. Ethics can, however, have an impact at any of several stages of a trial
when the individuals involved are committed. This editorial provides historical
examples of ignoring, evading or, alternatively, using ethical help to improve
clinical trials, and suggests that the actual role of ethics depends on the
individuals involved.
PMID- 26414552
TI - Probing chromium(III) from chromium(VI) in cells by a fluorescent sensor.
AB - Cellular uptake of Cr(VI), followed by its reduction to Cr(III) with the
formation of kinetically inert Cr(III) complexes, is a complex process. To better
understand its physiological and pathological functions, efficient methods for
the monitoring of Cr(VI) are desired. In this paper a selective fluorescent probe
L, rhodamine hydrazide bearing a benzo[b]furan-2-carboxaldehyde group, was
demonstrated as a red chemosensor for Cr(III) at about 586 nm. This probe has
been used to probe Cr(III) which is reduced from Cr(VI) by reductants such as
glutathione (GSH), vitamin C, cysteine (Cys), H2O2 and Dithiothreitol (DTT) by
fluorescence spectra. Cr(VI) metabolism in vivo is primarily driven by Vc and
GSH. Vc could reduce CrO4(2-) to Cr(III) in a faster rate than GSH. The
indirectly detection limit for Cr(VI) by L+GSH system was determined to be 0.06
MUM at pH=6.2. Moreover, the confocal microscopy image experiments indicated that
Cr(VI) can be reduced to Cr(III) inside cells rapidly and the resulted Cr(III)
can be captured and imaged timely by L.
PMID- 26414553
TI - Synthesis and multi-spectroscopic DNA binding study of 1,3,4-oxadiazole and 1,3,4
thiadiazole derivatives of fatty acid.
AB - A facile and convenient synthesis of a series of fatty acid derivatives of 1,3,4
oxadiazole and 1,3,4-thiadiazole has been described. The key step of this
protocol is the cyclization of acyl thiosemicarbazides via iodobenzene diacetate
and methanesulfonic acid under mild conditions. The newly synthesized compounds
were characterized by FT-IR, (1)HNMR, (13)CNMR and mass spectral study. The
binding affinity of 5-(pentadecyl)-N-propenyl-1,3,4-oxadiazol-2-amine (3a) and 5
(heptadecyl)-2-amino-1,3,4-thiadiazole (6a) with CT-DNA has been evaluated by UV,
fluorescence, Circular Dichroism (CD) and thermal denaturation studies. It has
been found that these small and planer heteroaromatic compounds are capable of
binding to the minor groove region of DNA.
PMID- 26414554
TI - 4-(8-quinolyl)amino-7-nitro-2,1,3-benzoxadiazole as a new selective and sensitive
fluorescent and colorimetric pH probe with dual-responsive ranges in aqueous
solutions.
AB - Fluorescent and colorimetric pH probe possess many advantages including rapid
response time, nondestructive testing, and excellent pH sensitivity. However,
they usually cannot be utilized simultaneously in both acidic and basic pH
ranges. In this study, a new selective and sensitive fluorescent and colorimetric
pH probe, 4-(8-quinolyl)amino-7-nitro-2,1,3-benzoxadiazole (1), was designated
and synthesized. The optical probe exhibited dual-responsive pH ranges to both
acidic and basic aqueous solutions. When the solution pH was gradually increased
from 8.5 to 13.3, the absorption spectra of 1 showed an obvious hyperchromicity,
accompanied with a red shift of the absorption band at 340 nm, a blue shift of
the absorption band at 482 nm, and a distinct color change from orange to violet
pink to yellow. Within the pH range from 2.2 to 0.2, the fluorescent spectra of 1
showed a "turn-on" response signal to solution pH. In order to understand the
response mechanism of the probe to solution pH, the probe molecule was split into
two parts, 8-aminoquinoline (2) and 4-amino-7- nitro-benzofurazan (3). UV-vis
absorption and fluorescent experiments of 2 and 3 indicated that both are
sensitive optical pH probes. Furthermore, the NMR experiment of 1 was explored in
basic and acidic conditions. The results indicated that the colorimetric
responses of 1 to pH under basic condition should be attributed to the
deprotonation of the imino group on the quinolyl ring, and the fluorescent
recognition of 1 to pH under acidic condition was probably due to the protonation
of the nitrogen atoms from the benzofurazan and quinolyl rings.
PMID- 26414555
TI - An insight into the metal coordination and spectroscopic properties of artistic
Fe and Fe/Cu logwood inks.
AB - Fe- and Fe/Cu-based logwood inks were synthesized following recipes in nineteenth
and early twentieth century manuals and were characterized by EPR, ESI-MS, FTIR,
and Raman spectroscopies. This multi-technique approach allowed us to shed light
on the structures of the complexes responsible for the inks' colors and to obtain
vibrational signatures that can be used to identify the different inks in works
of art and in historic documents. Information on the nature and chemical
properties of the complexes formed between a dye and a mordant is important as
these determine, at least in part, their lightfastness. EPR permitted to
determine the coordination environment of the metallic ions. The results of the
ESI-MS analysis demonstrated, for the first time, the breakdown of the hematein
molecule during the ink preparation, and that the colorants are formed by the
complexation of the metallic ions by hematein breakdown products, mainly catechol
and/or bicyclic compounds. The FTIR spectra obtained were found to be dominated
by bands due to the binding medium and sulfates used as reagents. The Raman
analysis showed that the characteristic features for the different inks studied
depend on the historic recipe used, attesting to the challenges that their
identification and characterization in works of art present. In the Raman spectra
of the inks applied on paper, broadening of bands in the 750-400 cm(-1) range are
observed when compared to the spectra of the inks' powders, possibly due to the
interaction of the compounds with the cellulose in the substrate.
PMID- 26414556
TI - Novel Rat Model of Weight Drop-Induced Closed Diffuse Traumatic Brain Injury
Compatible with Electrophysiological Recordings of Vigilance States.
AB - Traumatic brain injury (TBI) is a major cause of persistent disabilities such as
sleep-wake disorders (SWD). Rodent studies of SWD after TBI are scarce, however,
because of lack of appropriate TBI models reproducing acceleration-deceleration
forces and compatible with electroencephalography/myography (EEG/EMG)-based
recordings of vigilance states. We therefore adapted the Marmarou impact
acceleration model to allow for compatibility with EEG-headset implantation.
After implantation of EEG/EMG electrodes, we induced closed TBI by a frontal,
angular hit with a weight-drop device (56 rats, weight 2500 g, fall height 25
cm). Subsequently, we tested our model's usefulness for long-term studies on a
behavioral, electrophysiological, and histological level. Neurological, motor,
and memory deficits were assessed with the neurological severity score, open
field, and novel object recognition tests, respectively. EEG/EMG recordings were
performed in both Sham (n = 7) and TBI (n = 7) rats before and 1, 7, and 28 days
after trauma to evaluate sleep-wake proportions and post-traumatic implant
stability. Histological assessments included hematoxylin and eosin staining for
parenchymal damage and hemorrhage and amyloid precursor protein staining for
diffuse axonal damage. All rats survived TBI without major neurological or motor
deficits. Memory function was impaired after TBI at weeks 1, 2, and 3 and
recovered at week 4. EEG implants were stable for at least 1 month and enabled
qualitative and quantitative sleep analyses. Histological assessments revealed no
major bleedings or necrosis but intense diffuse axonal damage after TBI. This
approach fulfills major pre-conditions for experimental TBI models and offers a
possibility to electrophysiologically study behavioral states before and after
trauma.
PMID- 26414557
TI - Myopic Shift during Hyperbaric Oxygenation Attributed to Lens Index Changes.
AB - PURPOSE: To examine ocular lens parameters and structural changes to elucidate
mechanisms underlying the myopic shift and cataract-related changes that occur in
some patients during hyperbaric oxygen (HBO) therapy. METHODS: Scheimpflug images
(Nidek EAS-1000) of the crystalline lens, measurements of scattered light,
objective refraction, keratometry, tonometry, and axial length of the eye were
obtained after the first day of HBO therapy and repeated when patients had
completed 19 days of the treatment. RESULTS: Significant reduction in mean (+/-
SD) optical density was found in the lens nucleus, -2.8 (+/- 4.3) units (p =
0.009) and -2.2 (+/- 4.1) units (p = 0.027) within circular and oval areas,
respectively. Significant decrease in mean (+/- SD) backward scattered light was
measured, -0.4 (+/- 0.8) units (p = 0.022). Mean (+/- SD) myopic shift was -0.58
(+/- 0.39) diopters (p < 0.001), whereas cortical optical density, forward
scattered light, lenticular parameters, keratometry, tonometry, anterior chamber
depth, and axial length of the eye appeared unchanged. CONCLUSIONS: Transient
myopic shift reported in patients during HBO therapy is attributed to changes in
the refractive index of the lens. No changes in lens curvatures or thickness were
found after treatment.
PMID- 26414558
TI - Inguinal Hernia Repair During Extraperitoneal Robot-Assisted Laparoscopic Radical
Prostatectomy.
AB - INTRODUCTION: One third of men undergoing radical prostatectomy have a comorbid
inguinal hernia (IH). Previous studies have shown that adding total
extraperitoneal (TEP) IH repair to extraperitoneal laparoscopic radical
prostatectomy (LRP) lacks adverse effects. However, outcomes of extraperitoneal
robot-assisted laparoscopic radical prostatectomy (RALP) and TEP are unknown. We
compared RALP+TEP with LRP+TEP and also with RALP alone. METHODS: Eleven RALP+TEP
cases were retrospectively compared with 26 LRP+TEP cases and 22 control RALP
without TEP. Outcomes compared between groups included operative time, estimated
blood loss (EBL), discharge hematocrit (hct), time to diet advancement, length of
hospital stay (LOS), postoperative complications, and hernia recurrence. RESULTS:
Unilateral TEP added 32 minutes to RALP and 31 minutes to LRP, whereas bilateral
TEP added 80 minutes to RALP and 36 minutes to LRP. There were no differences
between RALP+TEP and LRP+TEP or RALP without TEP controls in regard to EBL,
discharge hct, time to diet advancement, LOS, or postoperative complications. One
patient developed an anterior mesh seroma, which resolved without intervention.
No IH recurrences were noted on the mean follow-up of 33 months in the RALP group
and 50 months in the LRP cohort. CONCLUSIONS: Unilateral and bilateral TEP added
operative time to RALP but had equivalent outcomes to both LRP+TEP and RALP
alone. This is likely due to the similar surgical space used for RALP and TEP,
which obviates the need for substantial further dissection. For men with prostate
cancer and comorbid IH, combined RALP+TEP appears to be an appropriate surgical
combination.
PMID- 26414559
TI - Characteristics of traumatic intracerebral haemorrhage: An assessment of
screening logs from the STITCH(Trauma) Trial.
AB - INTRODUCTION: In undertaking international neurosurgical trials it is useful to
understand international patient demographics and potential patient populations
that study results will apply to. The STITCH(Trauma) trial included 59 centres
from 20 countries, which were requested to screen all patients with traumatic
intracerebral haemorrhage. This paper reviews these data. MATERIALS AND METHODS:
Demographic, clinical and exclusion reason data were analysed. Comparisons were
made between patients who were included in the trial and patients who were
potentially eligible (but not included in the trial) and patients who were not
potentially eligible. RESULTS: Screening evidence was returned for 1735 patients,
11% of these may potentially have been eligible, of whom 52% were not included
because consent could not be gained. By country, median age per centre ranged
from 26 years (Egypt) to 67 years (Germany), median time from injury to screening
ranged from 5 h (Germany and Nepal) to 16 h (India), median intracerebral
haemorrhage (ICH) volume ranged from 5 ml (Germany) to 30 ml (China), the
proportion of male patients ranged from 56% (Egypt) to 91% (Canada) and the
proportion of patients with both pupils reactive ranged from 68% (China) to 98%
(Nepal). The most common exclusion reasons were ICH volume < 10 ml (49%) and
presence of subdural haemorrhage/extradural haemorrhage or SDH/EDH requiring
surgery (20%). CONCLUSION: Data presented here including international patient
demographics and reasons for patient ineligibility will be useful for future
traumatic ICH studies.
PMID- 26414560
TI - What the obesity prevention field can learn from the gay marriage movement.
PMID- 26414561
TI - Liver Fibrosis Predicts Cognitive Function Following Bariatric Surgery: A
Preliminary Investigation.
AB - OBJECTIVE: Obesity is a well-established risk factor for poor neurological
outcomes, and bariatric surgery has been shown to improve many aspects of
cognitive function. Factors underlying improved cognition following surgery are
not yet fully established. A recent study of bariatric surgery patients
demonstrated lower preoperative alkaline phosphatase concentrations were linked
to greater postoperative cognitive improvement, but this link has not been
examined via liver biopsy. The current study examined postoperative cognitive
function in individuals with and without fibrosis at the time of bariatric
surgery. It expected that those with fibrosis would demonstrate poorer
postoperative cognition. METHODS: Thirty-six bariatric surgery patients underwent
routine liver biopsy at the time of surgery and completed cognitive testing 1
month postoperatively. RESULTS: Bariatric surgery patients with fibrosis
demonstrated poorer performance on a task of executive function (maze errors, P =
0.01) and verbal memory (recognition memory, P = 0.01). CONCLUSIONS: Bariatric
surgery patients with fibrosis demonstrated poorer cognition following surgery,
providing further evidence for the connection between liver disease and cognitive
function. Future work examining mechanisms underlying bariatric postoperative
cognitive changes should include examination of broader metabolic functions,
particularly liver function.
PMID- 26414562
TI - Effect of Duodenal-Jejunal Bypass Surgery on Glycemic Control in Type 2 Diabetes:
A Randomized Controlled Trial.
AB - OBJECTIVE: To determine whether upper gastrointestinal tract (UGI) bypass itself
has beneficial effects on the factors involved in regulating glucose homeostasis
in patients with type 2 diabetes (T2D). METHODS: A 12-month randomized controlled
trial was conducted in 17 overweight/obese subjects with T2D, who received
standard medical care (SC, n = 7, BMI = 31.7 +/- 3.5 kg/m(2) ) or duodenal
jejunal bypass surgery with minimal gastric resection (DJBm) (n = 10; BMI = 29.7
+/- 1.9 kg/m(2)). A 5-h modified oral glucose tolerance test was performed at
baseline and at 1, 6, and 12 months after surgery or starting SC. RESULTS: Body
weight decreased progressively after DJBm (7.9 +/- 4.1%, 9.6 +/- 4.2%, and 10.2
+/- 4.3% at 1, 6, and 12 months, respectively) but remained stable in the SC
group (P < 0.001). DJBm, but not SC, improved: (1) oral glucose tolerance
(decreased 2-h glucose concentration, P = 0.039), (2) insulin sensitivity
(decreased homeostasis model assessment of insulin resistance, P = 0.013), (3)
early insulin response to a glucose load (increased insulinogenic index, P =
0.022), and (4) overall glycemic control (reduction in HbA1c with fewer diabetes
medications). CONCLUSIONS: DJBm causes moderate weight loss and improves
metabolic function in T2D. However, our study cannot separate the benefits of
moderate weight loss from the potential therapeutic effect of UGI tract bypass
itself on the observed metabolic improvements.
PMID- 26414563
TI - Frequent Self-Weighing with Electronic Graphic Feedback to Prevent Age-Related
Weight Gain in Young Adults.
AB - OBJECTIVE: An intervention using Wi-Fi scales and graphic e-mail feedback, the
caloric titration method (CTM), to reduce age-related weight gain over 1 year
among college students was evaluated. METHODS: First-year college students (n =
167) were randomized to CTM or control (C) groups and provided Wi-Fi scales. The
CTM group was instructed to weigh daily, view a weight graph e-mailed to them
after weighing, and try to maintain their weight. The C group could weigh at any
time but did not receive feedback. At 6 months and 1 year, the C group provided
weights. For intention to treat analysis, an adjusted mixed model was used to
analyze the effect of the intervention. RESULTS: Baseline body mass index was
22.9 +/- 3.0 kg/m(2) . Ninety-five percent of the CTM participants weighed >= 3
times/week, compared to 15% in the C group (P < 0.001). After 1 year, the C group
had gained 1.1 +/- .4 kg whereas the CTM group lost 0.5 +/- 3.7 kg (F = 3.39, P =
0.035). The difference in weight change between the two groups at 1 year was
significant (P = 0.004). Retention was 81%. CONCLUSIONS: CTM intervention was
effective in preventing age-related weight gain in young adults over 1 year and
thus offers promise to reduce overweight and obesity.
PMID- 26414565
TI - Erratum: Cannabis use in relation to obesity and insulin resistance in the inuit
population.
PMID- 26414564
TI - The Human Circadian System Has a Dominating Role in Causing the Morning/Evening
Difference in Diet-Induced Thermogenesis.
AB - OBJECTIVE: Diet-induced thermogenesis (DIT) is lower in the evening and at night
than in the morning. This may help explain why meal timing affects body weight
regulation and why shift work is a risk factor for obesity. The separate effects
of the endogenous circadian system--independent of behavioral cycles--and of
circadian misalignment on DIT are unknown. METHODS: Thirteen healthy adults
undertook a randomized crossover study with two 8-day laboratory visits: three
baseline days followed either by repeated simulated night shifts including 12-h
inverted behavioral cycles (circadian misalignment) or by recurring simulated day
shifts (circadian alignment). DIT was determined for up to 114 min (hereafter
referred to as "early DIT") following identical meals given at 8AM and 8PM in
both protocols. RESULTS: During baseline days, early DIT was 44% lower in the
evening than morning. This was primarily explained by a circadian influence
rather than any behavioral cycle effect; early DIT was 50% lower in the
biological evening than biological morning, independent of behavioral cycle
influences. Circadian misalignment had no overall effect on early DIT.
CONCLUSIONS: The circadian system plays a dominating role in the morning/evening
difference in early DIT and may contribute to the effects of meal timing on body
weight regulation.
PMID- 26414566
TI - Occupational stress in oncology nurse caregiving: caring for ourselves.
AB - The emotional work of oncology nurses is complex. Inherent in our job is the
requirement to be exquisitely empathic. We must look after, respond to, and
support numerous patients and their families. Fully present, we repeatedly listen
to stories of sadness and despair. Intermittently, we must either display or
suppress our emotions. All of this takes place in an occupational environment
where support for the nurses' emotional well-being is nonexistent. Lacking are
opportunities to vent emotions, sufficient time to grieve patients' deaths, and
resources to help nurses cope with work-related stress.
PMID- 26414567
TI - Oncology nurses need to get serious about cancer rehabilitation?.
AB - Patients with cancer suffer greatly. Rehabilitation helps them suffer less, and
yet very few patients with cancer get rehabilitation services of any kind.
Oncology nurses are well positioned to see the toll that cancer and its treatment
take on patients and to facilitate appropriate supportive care, including
rehabilitation.?.
PMID- 26414568
TI - Interventions to treat malignant pleural effusions.
AB - Malignant pleural effusions (MPEs) are common complications that occur with
advanced stages of cancer. In general, they indicate a poor prognosis and greatly
affect quality of life (QOL). The treatment goal of MPEs is to provide relief of
symptoms. The standard treatment for MPEs is talc pleurodesis; however,
indwelling pleural catheters have become more frequently used. This article
focuses on current management strategies for MPEs and assesses their influence on
QOL.At a GlanceSymptoms of malignant pleural effusions (MPEs), which involve the
accumulation of fluid in the pleural space, include dyspnea, shortness of breath,
chest pain, and other issues that decrease functional status.Treatment for MPEs
should be palliative, achieving immediate symptom relief and improved quality of
life.The optimal treatment strategy for MPEs should have minimal side effects,
require minimal or no hospitalization, and have low rates of recurrence.
PMID- 26414569
TI - Impact of a nurse navigator on genomic testing and timely treatment decision
making in patients with breast cancer.
AB - The purpose of this quality improvement project was to define best practices for
identifying appropriate patients for genomic testing and improve timeliness for
ordering tests and reporting results. An interdisciplinary team of surgeons,
radiologists, medical oncologists, and nurses agreed that the RN navigator would
be the key person to facilitate timely access to genomic profiling. AT A GLANCE:
Genomic profiling has become the standard of care for patients with early-stage
breast cancer to assist in developing individualized treatment plans. Nurse
navigators can play a key role in improving timeliness of care. The APN-RN model
led to improvements in turnaround time and complicance with the National
Comprehensive Cancer Network's recommendations for genomic testing.
PMID- 26414570
TI - Evaluating the frequency of vital sign monitoring during blood transfusion: an
evidence-based practice initiative.
AB - Patients with cancer are often dependent on blood transfusions during treatment.
Frequent vital sign monitoring during transfusions may interrupt sleep and the
patient's ability to ambulate or participate in unit activities. Relying heavily
on vital sign findings may also overshadow unmeasurable symptoms of transfusion
reaction. The aim of this evidence-based practice initiative was to examine the
evidence regarding the optimum frequency of vital sign monitoring for patients
undergoing stem cell transplantation receiving blood products and to amend policy
and practice to be consistent with the literature. ?AT A GLANCE?: Patients with
cancer frequently require transfusion support during treatment.Inconsistencies
exist in recommendations for the frequency of vital sign monitoring during
transfusion.Examining best practice guidelines suggests that less frequent vital
sign monitoring may be appropriate if coupled with thoughtful physiologic
assessment.
PMID- 26414571
TI - Proton beam therapy for pediatric malignancies.
AB - Although major advances have been made in radiation techniques, concerns still
exist about the treatment-related acute and long-term side effects. This issue is
most notable in the pediatric population because of developing organs and tissues
combined with longer life expectancies. Proton beam therapy has the advantage of
a reduced dose of radiation with less scatter to normal tissue, which may lead to
fewer adverse side effects.?AT A GLANCE: Many pediatric patients with cancer
receive radiation therapy.Radiation treatments can cause significant acute and
long-term side effects.Proton beam therapy reduces radiation scatter to normal
tissues and may decrease acute and late toxicities.
PMID- 26414572
TI - Preventing chemotherapy errors with comprehensive medication assessment.
AB - Preventing medication and chemotherapy errors is a priority in oncology nursing.
In this article, a case is presented detailing a medication error that occurred
because of inadequate assessment. Such errors still can occur despite electronic
systems designed to increase medication administration safety. The authors will
discuss implications for oncology nurses.?AT A GLANCE: Chemotherapy errors can
occur if the American Society of Clinical Oncology and Oncology Nursing Society
chemotherapy administration guidelines are not practiced consistently.?Failure to
observe the 10 principles of medication administration contributes to
chemotherapy errors.?Electronic safeguards may not prevent chemotherapy errors.?.
PMID- 26414573
TI - A systematic review of nonpharmacologic interventions for treatment-related
symptoms in women with ovarian cancer.
AB - BACKGROUND: Women with ovarian cancer have a continued high symptom burden in
comparison to other cancer survivors secondary to ongoing chemotherapy treatment.
Prolonged or ineffective management of treatment-related symptoms can contribute
to treatment noncompliance, worsening of symptoms, and reduced health-related
quality of life. OBJECTIVES: This review of the literature was conducted to
describe experimental and quasi-experimental research addressing nonpharmacologic
interventions for the treatment-related symptoms of sleep disturbance, pain,
anxiety, depression, and low energy or fatigue in women with ovarian cancer and
to critique the quality of interventions. METHODS: A systematic search of the
literature was conducted in PubMed and yielded 136 articles. Eight articles met
the inclusion criteria and were evaluated. FINDINGS: Nonpharmacologic
interventions for treatment-related symptoms were complex, with an average of 4.4
components. Intervention delivery, setting, and exposure varied widely across
studies. Only three studies contained details sufficient to replicate the
intervention. Lack of clarity in intervention reporting may explain perceptions
of clinically inefficacious symptom management in this context. Greater attention
to reporting would facilitate better translation of interventions into practice
and when addressing complex cancer symptom clusters.
PMID- 26414574
TI - The evolving role of the nurse during the cancer treatment decision-making
process: a literature review.
AB - BACKGROUND: Many models of patient-physician relationships have been described
since a paternalistic model was postulated in the early 1950s. Among them are the
informative model, doctor-as-agent model, shared model of care, family-centered
model, and Degner and Beaton's Patterns of Decision Making. OBJECTIVES: This
article aims to examine the contemporary role of the nurse during the cancer
treatment decision-making process. METHODS: This article reviews the current and
evidence-based role of the nurse during cancer treatment decision making, and
implications for practice and research are discussed. FINDINGS: Because of
external forces, such as rising cost of health care, increasing healthcare
consumerism, and increased emphasis on patient-centered care, the shared model of
care is taking hold, particularly in the cancer setting. The evolution of these
models has caused a shift in the dialogue related to cancer treatment decision
making between patients and physicians, as well as oncology nurses. These events
contribute to the evolving role of the nurse during the cancer treatment decision
making process.
PMID- 26414575
TI - An oncology nurses' guide to new targeted agents for metastatic colorectal
cancer.
AB - BACKGROUND: Colorectal cancer (CRC) that has metastasized before being
discovered, or reoccurs following surgery, remains a major treatment challenge.
Trials have established the usefulness of antiangiogenic agents and new regimens
in prolonging survival in patients with advanced disease. In the United States,
the antiangiogenic agents approved for treating metastatic CRC often are combined
with traditional chemotherapeutic agents and include bevacizumab (Avastin(r)),
ziv-aflibercept (Zaltrap(r)), and regorafenib (Stivarga(r)). OBJECTIVES: This
article reviews factors that guide the development of a nursing plan for
monitoring and managing patients who are receiving antiangiogenic therapies.
METHODS: Regorafenib and ziv-aflibercept, two newer agents that nurses and other
healthcare professionals may have had less experience with, were reviewed.
FINDINGS: The key to maximizing the potential benefit of these agents is
understanding where these new therapies fit in the overall scheme of treatment
options and how to help patients tolerate treatment.
PMID- 26414576
TI - Delirium in patients with cancer: what nurses need to know to improve care.
AB - BACKGROUND: Delirium is a serious problem when caring for a patient with cancer
in the hospital. Delirium causes major risks and concerns for patients, family
members, and healthcare workers, and it often goes unrecognized and has many
clinical manifestations. OBJECTIVES: This article aims to evaluate whether a
nursing educational program on the topic of delirium would increase the nursing
staff's knowledge and confidence in managing patients with delirium. METHODS: A
repeated-measures research design using general linear modeling was used for this
study. An evidence-based delirium protocol and an educational session were
developed for the nursing staff on an inpatient medical-surgical oncology unit.
The nurses attended a delirium educational session to learn about risk factors,
prevention, assessment, and management of delirium, as well as the use of the
delirium protocol. FINDINGS: The nursing educational program on the topic of
delirium increased the nursing staff's knowledge from 69% to 86%, and overall
confidence in managing patients with delirium increased from 47% to 66%. This
study confirms the benefits of delirium education in the inpatient medical
surgical oncology setting.
PMID- 26414577
TI - Self-reported assessment of symptoms and self-care within a cohort of U.S.
veterans during outpatient care for cancer.
AB - BACKGROUND: This study was undertaken as part of a feasibility study of the use
of a symptom checklist and self-care assessment of veterans receiving oncology
outpatient treatment within the U.S. Department of Veterans Affairs system.
OBJECTIVES: The study aimed to examine (a) symptom occurrence and severity as
self-reported on the Therapy-Related Symptom Checklist (TRSC) by veterans at a
cancer clinic, (b) symptom alleviation strategies and use of self-care, and (c)
the relationship between symptom occurrence and severity and functional status
and quality of life. METHODS: Veterans (N = 100) undergoing chemotherapy and/or
radiation therapy participated in a cross-sectional study. Tools used, including
TRSC, Symptom Alleviation. FINDINGS: Thirteen symptoms were reported by more than
35% of patients. Top-ranked symptoms by percentage occurrence and severity were
feeling sluggish, taste changes, nausea, pain, constipation, loss of appetite,
numbness of fingers and toes, difficulty sleeping, weight loss, hair loss,
difficulty concentrating, shortness of breath, and decreased interest in sexual
activity. Occurrence and severity of symptoms had significant negative
correlations with functional status and with overall quality of life. Self-care
(symptom alleviation) strategies that helped were medicines, diet and nutrition,
and lifestyle change. Checklist use (TRSC) facilitated patient-report of symptoms
during cancer treatments; self-care strategies helped relieve symptoms.
PMID- 26414578
TI - Breast cancer genetic testing: more than a medical management tool.
AB - BACKGROUND: Knowing whether a harmful hereditary mutation exists in BRCA1 and
BRCA2 can enable women to make informed decisions regarding surveillance and
surgery options to manage risk. Given the attention in the media about BRCA
genetic testing, nurses need to revisit how this knowledge may affect a woman's
sense of self and the forces that may influence this decision. OBJECTIVES: This
article aims to understand how complex the decision to undergo genetic testing
may be for some women by exploring the impact of genetic knowledge on the self,
changes to customary definitions for health and illness, and ethical issues and
social forces that may influence genetic testing decisions. METHODS: A review of
the literature was undertaken to understand how genetic knowledge may alter
meanings attached to the breast and how health is defined, and to identify
ethical concerns and social forces that may affect a woman's decision to undergo
or decline an offer for genetic testing. FINDINGS: An understanding and awareness
of the potential benefits and harms of BRCA1 and BRCA2 genetic testing, as well
as the social forces that may influence a woman's decision to undergo or decline
an offer for genetic testing and the commitment to remain open to the uniqueness
of each woman's situation, may enhance the nurse-patient relationship and result
in a decision that is ethically in the best interest of the patient.
PMID- 26414579
TI - Australian experience of neuro-oncology care coordination: a conversation.
AB - BACKGROUND: The role of care coordinator was introduced to support patients,
caregivers, and healthcare professionals who work within a specialty, as well as
to optimize and standardize care. Specifically, the role of neuro-oncology care
coordinator is a developing one-and one that has encountered various barriers and
difficulties. Patients diagnosed with neurologic cancer must endure a disease
trajectory and multimodal treatment approach that present unique challenges to
themselves and to the healthcare system. Consequently, the care coordinator role
is needed. OBJECTIVES: This article focuses on the role of the neuro-oncology
care coordinator, including its challenges, the needs of patients with neurologic
cancer, and the benefits this role can bring. METHODS: Three neuro-oncology care
coordinators from New South Wales, Australia, discussed their role in the
healthcare system via structured meetings, conversations, and email
correspondence. FINDINGS: Making others aware of the issues faced by neuro
oncology care coordinators, as well as their patients, may help to solidify
necessary supportive roles within the healthcare system.
PMID- 26414580
TI - Integrating oral health throughout cancer care.
AB - Oral health is often not a priority during cancer treatment; however, patients
with cancer are at increased risk for oral complications during and after
treatment. This article focuses on the importance of oral health care before,
during, and after cancer treatment using the head, eyes, ears, nose, oral cavity,
and throat, or HEENOT, approach. AT A GLANCE: Oral health is linked to overall
health, and healthcare providers must be cognizant of the oral-systemic
connection with patients undergoing cancer treatment, which may cause acute and
chronic oral health problems. ?Oral assessment, prevention, early recognition,
and treatment of oral problems must be incorporated into cancer care,
particularly with the aid of an interprofessional team to meet patients' oral
care needs. ?The head, eyes, ears, nose, oral cavity, and throat, or HEENOT,
approach integrates oral care into patients' history taking, physical
examination, and plan of cancer care.?.
PMID- 26414581
TI - Yttrium-90 radioembolization as a palliative treatment for liver tumors: a case
study.
AB - The best chance of cure for patients with liver cancer is surgical removal, but
many tumors are too large or invasive. In addition, chemotherapy is frequently
unsuccessful in this patient population. A case study is featured involving a
patient determined to be a candidate for Yttrium-90 radioembolization, a
minimally invasive liver-directed treatment used to target primary and metastatic
liver tumors by delivering radioactive microspheres directly to the tumor. This
article provides an introduction to the procedure, as well as practical
information for nurses caring for patients with liver cancer following Yttrium-90
radioembolization.AT A GLANCE: Yttrium-90 radioembolization allows larger
radiation doses to be used without affecting healthy tissues.An outpatient
procedure, Yttrium-90 radioembolization results in fewer side effects than
standard treatment.?Although Yttrium-90 radioembolization can extend and improve
quality of life, its intent is palliative, not curative.
PMID- 26414582
TI - Evaluation of a web course to increase evidence-based practice knowledge among
nurses.
AB - Evidence-based practice (EBP) is essential for quality health care, and EBP
knowledge needs to be increased among nurses. Web-based courses may effectively
deliver such education. In this study, data were collected about the Oncology
Nursing Society web course "Developing Skills for Evidence-Based Practice" and
evaluated for demographic characteristics and EBP knowledge test scores.?AT A
GLANCE: No significant correlation was seen between knowledge test scores and
participants' education or experience levels.Course participants had significant
improvement on knowledge test scores after web course completion.?Additional
studies are needed to explore the impact of EBP knowledge on clinical practice.
PMID- 26414583
TI - Prophylactic antibiotics to prevent surgical site infection after breast cancer
surgery.
AB - This systematic review includes 11 randomized, controlled trials of mixed patient
groups, including patients with or without breast cancer. Studies were included
in the review only if data from patients with breast cancer could be separated
from patients without breast cancer. The intervention included pre- or
perioperative antibiotics used as prophylaxis for the surgery. A range of
antibiotic regimens were assessed in the 11 studies, and 5 of the studies defined
a similar antibiotic strategy. Five of the studies had similar choice of
antibiotic, type of surgery, and length of follow-up. The reviewers excluded 27
studies because of design and data collection not matching the review
requirements.
PMID- 26414584
TI - Caring, sharing, and a friendship made for life.
AB - A patient named "Bill" was assigned to my team in the summer of 2012 for an
autologous stem cell transplantation for lymphoma. Bill had previous chemotherapy
and had attained clinical status eligibility for a transplantation. Although Bill
was rather quiet, he had a lot of questions about me, my family, and my travels.
In turn, he shared about his work as a veterinarian, his clinic, and his two dogs
that went everywhere with him. He also shared his love of the outdoors and
traveling, highlighted by a trip on the Amazon River with his father and
daughter. I told him that one of my hobbies is making dill pickles. He countered
with stories about his bees and honey, and we agreed to share our homemade goods.
PMID- 26414585
TI - A concept analysis of nurses' grief.
AB - BACKGROUND: The psychological and personal well-being of nurses can change the
way they care for patients. If nurses' grief is not properly managed, the nursing
shortage will continue to grow. Consequently, a need exists for the
identification of nurses' grief and effective interventions to manage grief to
ensure the successful development and growth of the nursing profession.
OBJECTIVES: This concept analysis sought to properly define nurses' grief and the
role it plays in the day-to-day requirements of nurses. METHODS: A review of the
literature was conducted using CINAHL(r), BioMed, EBSCOhost, and MEDLINE(r) and
the following key words. FINDINGS: Nurses' grief must be incorporated into the
nursing curriculum and addressed by employers. In particular, facility leaders
should help promote a healthy work environment and address the need for proper
grief management. Educators, managers, and nurses can benefit from acknowledging
the current gap in managing nurses' grief.
PMID- 26414586
TI - Analysis of denosumab on skeletal-related events in patients with advanced breast
cancer.
AB - BACKGROUND: Bisphosphonates, which are also known as osteoclast modifiers, are
the standard of care in the treatment of skeletal-related events (SREs) in
patients with breast cancer with metastatic bone disease. SREs are frequently a
complication of advanced breast cancer, and they greatly increase morbidity and
mortality in these patients. Unfortunately, even while undergoing bisphosphonate
therapy, many patients experience SREs. In 2010, a fully human monoclonal
antibody, denosumab (Xgeva(r)), was approved by the U.S. Food and Drug
Administration as another option to treat SREs. OBJECTIVES: This article analyzes
four primary human research studies looking at the effectiveness and safety of
denosumab as compared to bisphosphonates in the prevention of SREs in this
vulnerable population. METHODS: Articles published from 2006-2012 were located
and reviewed through online database searches (CINAHL(r), MEDLINE(r), PubMed
Plus) using the key words denosumab, skeletal-related event, breast cancer,
metastases, and bisphosphonates. FINDINGS: Studies reviewed showed comparative
adverse events and safety profile between denosumab and bisphosphonates. However,
denosumab was shown to have increased effectiveness in the prevention of SREs.
This knowledge can influence the preventive measures taken by physicians and
advanced practice nurses to improve the prevention of SREs in patients with
metastatic breast cancer. It can also increase staff nurse knowledge and
implementation of evidence-based practice.
PMID- 26414587
TI - Oral intake of ginger for chemotherapy-induced nausea and vomiting among women
with breast cancer.
AB - BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is among the most
common and distressing symptoms experienced by patients receiving cancer
treatment. Nurses play a substantial role in the prevention and management of
CINV. Ginger (Zingiber officinale Roscoe) is often advocated as beneficial for
nausea and vomiting. Whether the herb is truly efficacious for this condition is,
however, still a matter of debate. OBJECTIVES: This experimental randomized,
controlled trial was done to assess the effect of ginger on chemotherapy-related
nausea and vomiting. METHODS: All patients in the study (N = 60) received
standard antiemetic drugs. The patients in the study group (n = 30) also received
oral ginger for the first three days of the chemotherapy cycle. No intervention
was performed in the control group (n = 30) except for the routine antiemetic
treatment. Nausea severity and the number of vomiting and retching episodes were
measured four times each day for the first five days of the chemotherapy cycle in
the patient diary. Nausea severity was evaluated using a numeric scale ranging
from 0 (no nausea) to 10 (very severe nausea). FINDINGS: The researchers analyzed
the five-day mean score of nausea severity and the number of vomiting and
retching episodes. Based on this comparison, nausea severity and the number of
vomiting episodes were significantly lower in the intervention group than in the
control group (p > 0.05). However, the change in the number of retching episodes
between the intervention and control groups was not statistically significant (p
> 0.05).
PMID- 26414588
TI - Exercise and the breast cancer survivor: the role of the nurse practitioner.
AB - BACKGROUND: Patients with cancer are living longer with their disease and have
improved survival rates because of early detection and more effective cancer
treatments. Lifestyle modification and exercise improve clinical outcomes in
breast cancer survivors. OBJECTIVES: Exercise has important implications for the
survivor and should be integrated into the aftercare trajectory of survivorship.
METHODS: A literature review of articles published from 2002-2014 was conducted
using the key words cancer survivor, survivorship, breast cancer, collaboration,
and exercise. PubMed, Cochrane Database of Systematic Reviews, and CINAHL(r)
databases were searched. FINDINGS: Nurse practitioners can build an environment
to motivate patients to exercise, empowering them to be active participants in
their own survivorship care. Collaboration is necessary to ensure that healthy
lifestyle choices, including exercise, are being discussed and implemented in
survivorship care plans to help optimize patient outcomes.
PMID- 26414590
TI - Venous thromboembolism: identifying patients at risk and establishing
prophylaxis.
AB - Venous thromboembolism (VTE) is a major cause of morbidity and mortality and is
associated with substantial healthcare costs. Identification of patients at risk
of developing VTE enables appropriate thromboprophylaxis to be implemented.
Although no predisposing risk factors can be identified in many patients in whom
VTE develops, most have at least one underlying risk factor which can be
categorized according to whether it confers low, moderate, or high risk. Clinical
trials have demonstrated the effectiveness of thromboprophylaxis, both non
pharmacological and pharmacological, in a host of medical settings and there is
sufficient evidence to support routine prophylaxis in many groups of patients.
The implementation of decision making tools based on risk factor assessment
improves the prescription of appropriate VTE prophylaxis. Nonetheless,
thromboprophylaxis is often inadequate, with haphazard risk assessment and
application of guidelines, leading to easily preventable instances of VTE. The
most commonly used agents for pharmacological thromboprophylaxis of VTE are low
dose unfractionated heparin; a low molecular weight heparin such as dalteparin,
enoxaparin or tinzaparin; fondaparinux; warfarin; or aspirin. However, these have
a number of drawbacks, principally the need for parenteral administration (with
heparins) and frequent coagulation monitoring (with warfarin). The optimal
anticoagulant would be orally administered, with a wide therapeutic window, rapid
onset of action, predictable pharmacodynamics and pharmacokinetics, minimal
interactions with food and other drugs, an ability to inhibit free and clot-bound
coagulation factors, low, non-specific binding, and no requirement for routine
coagulation monitoring or dose adjustment. A number of novel, single-target oral
anticoagulants have been developed that appear to fulfill many of these
requirements. This narrative review discusses the use of guidelines and risk
assessment tools to identify patients at risk of VTE; it provides an overview of
appropriate prophylaxis strategies in these patients with a summary of clinical
trial results with novel oral anticoagulants.
PMID- 26414592
TI - Synthesis of 2,5-Dihydrofurans via a Gold(I)-Catalyzed Formal [4 + 1]
Cycloaddition of alpha-Diazoesters and Propargyl Alcohols.
AB - A gold(I)-catalyzed formal [4 + 1] cycloaddition of alpha-diazoesters and
propargyl alcohols is disclosed, offering access to a variety of 2,5
dihydrofurans. The reaction shows a broad substrate scope and functional group
tolerance. Preliminary mechanistic investigation indicates that this reaction
most likely occurs through a 5-endo-dig cyclization of an alpha-hydroxy allene
intermediate.
PMID- 26414591
TI - Manganese-Enhanced Magnetic Resonance Imaging as a Diagnostic and Dispositional
Tool after Mild-Moderate Blast Traumatic Brain Injury.
AB - Traumatic brain injury (TBI) caused by explosive munitions, known as blast TBI,
is the signature injury in recent military conflicts in Iraq and Afghanistan.
Diagnostic evaluation of TBI, including blast TBI, is based on clinical history,
symptoms, and neuropsychological testing, all of which can result in misdiagnosis
or underdiagnosis of this condition, particularly in the case of TBI of mild-to
moderate severity. Prognosis is currently determined by TBI severity, recurrence,
and type of pathology, and also may be influenced by promptness of clinical
intervention when more effective treatments become available. An important task
is prevention of repetitive TBI, particularly when the patient is still
symptomatic. For these reasons, the establishment of quantitative biological
markers can serve to improve diagnosis and preventative or therapeutic
management. In this study, we used a shock-tube model of blast TBI to determine
whether manganese-enhanced magnetic resonance imaging (MEMRI) can serve as a tool
to accurately and quantitatively diagnose mild-to-moderate blast TBI. Mice were
subjected to a 30 psig blast and administered a single dose of MnCl2
intraperitoneally. Longitudinal T1-magnetic resonance imaging (MRI) performed at
6, 24, 48, and 72 h and at 14 and 28 days revealed a marked signal enhancement in
the brain of mice exposed to blast, compared with sham controls, at nearly all
time-points. Interestingly, when mice were protected with a polycarbonate body
shield during blast exposure, the marked increase in contrast was prevented. We
conclude that manganese uptake can serve as a quantitative biomarker for TBI and
that MEMRI is a minimally-invasive quantitative approach that can aid in the
accurate diagnosis and management of blast TBI. In addition, the prevention of
the increased uptake of manganese by body protection strongly suggests that the
exposure of an individual to blast risk could benefit from the design of improved
body armor.
PMID- 26414593
TI - Ultrasound-Guided Transgluteal Percutaneous Nephrolithotomy for a Patient with
Complex Urogenital Reconstruction and Ectopic Kidney.
AB - BACKGROUND AND PURPOSE: Pediatric patients with urolithiasis and complex
reconstructed genitourinary anatomy pose a significant surgical challenge. We
describe a technique utilized to treat an obstructing calculus in the ectopic
kidney of a patient with a history of cloacal exstrophy, bladder augmentation,
Monti catheterizable channel, and reconstructed abdominal wall. Case and
Technique: A 5-year-old female with a history of cloacal exstrophy, pelvic
kidney, and reconstructed urologic and abdominal wall anatomy presented after
prior shockwave lithotripsy with an obstructing ureteropelvic junction calculus
with signs of sepsis. Because of the patient's previous abdominal wall
reconstruction with polytetrafluoroethylene mesh and the location of her pelvic
kidney, traditional methods of percutaneous nephrostomy tube placement could not
be performed. Transgluteal percutaneous nephrostomy tube was placed by
interventional radiology. Subsequently, a percutaneous nephrolithotomy (PCNL) was
performed through this tract. CONCLUSIONS: Transgluteal PCNL is a feasible option
in children with complex congenital genitourinary anomalies with a history of
reconstructed anatomy.
PMID- 26414595
TI - Managing hospitalized hemodialysis patients: A guide for the non-nephrologist.
AB - In-hospital care of end-stage renal disease (ESRD) patients, on hemodialysis, is
different from the general population in various aspects. Non-nephrologists do
not typically receive specialized training to take care of these patients.
However, in most circumstances, they serve as the primary attending for these
patients in the hospital setting. There is paucity of the literature guiding non
nephrologists on this important issue. This article highlights the key management
aspects of in-hospital care of these patients that all the non-nephrologists
should know.
PMID- 26414594
TI - Postoperative atrial fibrillation in patients undergoing non-cardiac non-thoracic
surgery: A practical approach for the hospitalist.
AB - New postoperative atrial fibrillation (POAF) is the most common perioperative
arrhythmia and its reported incidence ranges from 0.4 to 26% in patients
undergoing non-cardiac non-thoracic surgery. The incidence varies according to
patient characteristics such as age, presence of structural heart disease and
other co-morbidities, as well as the type of surgery performed. POAF occurs as a
consequence of adrenergic stimulation, systemic inflammation, or autonomic
activation in the intra or postoperative period (e.g. due to pain, hypotension,
infection) in the setting of a susceptible myocardium and other predisposing
factors (e.g. electrolyte abnormalities). POAF develops between day 1 and day 4
post-surgery and it is often considered a self-limited entity. Its acute
management involves many of the same strategies used in non-surgical patients but
the optimal long-term management is challenging because of the limited available
evidence. Several studies have shown an association between occurrence of POAF
and in-hospital morbidity, mortality, and length of stay. Although,
traditionally, POAF was considered to have a generally favorable long-term
prognosis, recent data have shown an association with an increased risk of stroke
at 1 year after hospitalization. It is unknown, however, whether strategies to
prevent POAF or for rate/rhythm control when it does occur, lead to a reduction
in morbidity or mortality. This suggests the need for future studies to better
understand the risks associated with POAF and to determine optimal strategies to
minimize long-term thromboembolic risks. In this article, we summarize the
current knowledge on epidemiology, pathophysiology, and short- and long-term
management of POAF after non-cardiac non-thoracic surgery with the goal of
providing a practical approach to managing these patients for the non
cardiologist clinician.
PMID- 26414597
TI - Interspecies quantitative structure-toxicity-toxicity (QSTTR) relationship
modeling of ionic liquids. Toxicity of ionic liquids to V. fischeri, D. magna and
S. vacuolatus.
AB - Considering the increasing uses of ionic liquids (ILs) in various industrial
processes and chemical engineering operations, a complete assessment of their
hazardous profile is essential. In the absence of adequate experimental data, in
silico modeling might be helpful in filling data gaps for the toxicity of ILs
towards various ecological indicator organisms. Using the rationale of taxonomic
relatedness, the development of predictive quantitative structure-toxicity
toxicity relationship (QSTTR) models allows predicting the toxicity of ILs to a
particular species using available experimental toxicity data towards a different
species. Such studies may employ, along with the available experimental toxicity
data to a species, molecular structure features and physicochemical properties of
chemicals as independent variables for prediction of the toxicity profile against
another closely related species. A few such interspecies toxicity correlation
models have been reported in the literature for diverse chemicals in general, but
this approach has been rarely applied to the class of ionic liquids. The present
study involves the use of IL toxicity data towards the bacteria Vibrio fischeri
along with molecular structure derived information or computational descriptors
like extended topochemical atom (ETA) indices, quantum topological molecular
similarity (QTMS) descriptors and computed lipophilicity measure (logk0) for the
interspecies exploration of the toxicity data towards green algae S. vacuolatus
and crustacea Daphnia magna, separately. This modeling study has been performed
in accordance with the OECD guidelines. Finally, predictions for a true external
set have been performed to fill the data gap of toxicity towards daphnids and
algae using the Vibrio toxicity data and molecular structure attributes.
PMID- 26414596
TI - Six-week follow-up after HIV-1 exposure: a position statement from the Public
Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy.
AB - In 2014 the Public Health Agency of Sweden and the Swedish Reference Group for
Antiviral Therapy (RAV) conducted a review and analysis of the state of knowledge
on the duration of follow-up after exposure to human immunodeficiency virus
(HIV). Up until then a follow-up of 12 weeks after exposure had been recommended,
but improved tests and new information on early diagnosis motivated a re
evaluation of the national recommendations by experts representing infectious
diseases and microbiology, county medical officers, the RAV, the Public Health
Agency, and other national authorities. Based on the current state of knowledge
the Public Health Agency of Sweden and the RAV recommend, starting in April 2015,
a follow-up period of 6 weeks after possible HIV-1 exposure, if HIV testing is
performed using laboratory-based combination tests detecting both HIV antibody
and antigen. If point-of-care rapid HIV tests are used, a follow-up period of 8
weeks is recommended, because currently available rapid tests have insufficient
sensitivity for detection of HIV-1 antigen. A follow-up period of 12 weeks is
recommended after a possible exposure for HIV-2, since presently used assays do
not include HIV-2 antigens and only limited information is available on the
development of HIV antibodies during early HIV-2 infection. If pre- or post
exposure prophylaxis is administered, the follow-up period is recommended to
begin after completion of prophylaxis. Even if infection cannot be reliably
excluded before the end of the recommended follow-up period, HIV testing should
be performed at first contact for persons who seek such testing.
PMID- 26414598
TI - Understanding the challenges of protein flexibility in drug design.
AB - INTRODUCTION: Protein-ligand interactions play key roles in various metabolic
pathways, and the proteins involved in these interactions represent major targets
for drug discovery. Molecular docking is widely used to predict the structure of
protein-ligand complexes, and protein flexibility stands out as one of the most
important and challenging issues for binding mode prediction. Various docking
methods accounting for protein flexibility have been proposed, tackling problems
of ever-increasing dimensionality. AREAS COVERED: This paper presents an overview
of conformational sampling methods treating target flexibility during molecular
docking. Special attention is given to approaches considering full protein
flexibility. Contrary to what is frequently done, this review does not rely on
classical biomolecular recognition models to classify existing docking methods.
Instead, it applies algorithmic considerations, focusing on the level of
flexibility accounted for. This review also discusses the diversity of docking
applications, from virtual screening (VS) of small drug-like compounds to
geometry prediction (GP) of protein-peptide complexes. EXPERT OPINION:
Considering the diversity of docking methods presented here, deciding which one
is the best at treating protein flexibility depends on the system under study and
the research application. In VS experiments, ensemble docking can be used to
implicitly account for large-scale conformational changes, and selective docking
can additionally consider local binding-site rearrangements. In other cases, on
the-fly exploration of the whole protein-ligand complex might be needed for
accurate GP of the binding mode. Among other things, future methods are expected
to provide alternative binding modes, which will better reflect the dynamic
nature of protein-ligand interactions.
PMID- 26414600
TI - Vascular Complications and Bleeding After Transfemoral Transcatheter Aortic Valve
Implantation Performed Through Open Surgical Access.
AB - Major vascular complications (VC) remain frequent after transcatheter aortic
valve implantation (TAVI) and may be associated with unfavorable clinical
outcomes. The objective of this study was to evaluate the rate of VC after
transfemoral TAVI performed using an exclusive open surgical access strategy.
From 2010 to 2014, we included in a monocentric registry all consecutive patients
who underwent transfemoral TAVI. The procedures were performed with 16Fr to 20Fr
sheath systems. VC were evaluated within 30 days and classified as major or minor
according to the Valve Academic Research Consortium 2 definition. The study
included 396 patients, 218 were women (55%), median age was 85 years (81 to 88),
and the median logistic Euroscore was 15.2% (11 to 23). The balloon-expandable
SAPIEN XT and the self-expandable Medtronic Core Valve prosthesis were used in
288 (72.7%) and 108 patients (27.3%), respectively. The total length of the
procedure was 68 +/- 15 minutes including 13 +/- 5 minutes for the open surgical
access. Major and minor VC were observed in 9 (2.3%) and 16 patients (4%),
respectively, whereas life-threatening and major bleeding concerned 18 patients
(4.6%). The median duration of hospitalization was 5 days (interquartile range 2
to 7), significantly higher in patients with VC (7 days [5 to 15], p <0.001).
Mortality at 1-month and 1-year follow-up (n = 26, 6.6%; and n = 67, 17.2%,
respectively) was not related to major or minor VC (p = 0.6). In multivariable
analysis, only diabetes (odds ratio 2.5, 95% confidence interval 1.1 to 6.1, p =
0.034) and chronic kidney failure (odds ratio 3.0, 95% confidence interval 1.0 to
9.0, p = 0.046) were predictive of VC, whereas body mass index, gender,
Euroscore, and lower limb arteriopathy were not. In conclusion, minimal rate of
VC and bleeding can be obtained after transfemoral TAVI performed using an
exclusive surgical strategy, with a particular advantage observed in high-risk
bleeding patients.
PMID- 26414602
TI - The Influence of Hypovolemia and Fluid Resuscitation During Hemorrhagic Shock on
Apneic Oxygen Desaturation After Preoxygenation in a Swine Model.
AB - BACKGROUND: Patients experiencing major bleeding often require both aggressive
fluid resuscitation and rapid sequence tracheal intubation. The influence of
hemorrhage-induced hypovolemia, and/or subsequent fluid resuscitation, on the
time until critical oxygen desaturation is not well described. We studied the
time to oxygen desaturation in a pig model of hemorrhage shock and colloid
resuscitation. METHODS: After anesthetic induction with isoflurane, 9 swine (mean
+/- SD = 25.3 +/- 0.6 kg) were studied with the use of a stepwise hemorrhage and
fluid resuscitation model with 4 sequential stages: 600 mL hemorrhage, 600 mL
hydroxyethyl starch infusion, a further 600 mL hemorrhage, and a second 600 mL
hydroxyethyl starch infusion. At each stage, after 5 minutes of mechanical
ventilation with 100% oxygen, we induced apnea and measured the time to oxygen
desaturation (oxygen saturation [SpO2] <70%). Hemodynamic and blood gas variables
were recorded, and the cerebral and peripheral tissue oxygenation indices were
recorded by near-infrared spectroscopy. RESULTS: The times +/- SD to SpO2 <70% at
each stage were 136 +/- 41 (baseline), 147 +/- 41 (hemorrhage), 131 +/- 38
(resuscitation), 147 +/- 38 (repeat hemorrhage), and 134 +/- 36 seconds (repeat
resuscitation). The mean differences in times before and after hemorrhage were
11.2 (6.5 to 16.0, P = 0.0052) and 16.0 (11.0 to 21.0, P < 0.0001), respectively.
PaO2 before and after apneic desaturation (at SpO2 < 70%) was not different
between stages. On the basis of tissue oxygenation index findings, hypovolemia
decreased oxygen consumption, and fluid resuscitation recovered this parameter.
CONCLUSIONS: In patients with acute hemorrhagic shock, a hypovolemic state
increases the duration of apnea until critical oxygen desaturation. Clinicians
should thus consider the relationship between fluid resuscitation and time to
desaturation when performing tracheal intubation in such patients.
PMID- 26414599
TI - In Vivo Evaluation of Adipose-Derived Stromal Cells Delivered with a Nanofiber
Scaffold for Tendon-to-Bone Repair.
AB - Rotator cuff tears are common and cause a great deal of lost productivity, pain,
and disability. Tears are typically repaired by suturing the tendon back to its
bony attachment. Unfortunately, the structural (e.g., aligned collagen) and
compositional (e.g., a gradient in mineral) elements that produce a robust
attachment in the healthy tissue are not regenerated during healing, and the
repair is prone to failure. Two features of the failed healing response are
deposition of poorly aligned scar tissue and loss of bone at the repair site.
Therefore, the objective of the current study was to improve tendon-to-bone
healing by promoting aligned collagen deposition and increased bone formation
using a biomimetic scaffold seeded with pluripotent cells. An aligned nanofibrous
poly(lactic-co-glycolic acid) scaffold with a gradient in mineral content was
seeded with adipose-derived stromal cells (ASCs) and implanted at the repair site
of a rat rotator cuff model. In one group, cells were transduced with the
osteogenic factor bone morphogenetic protein 2 (BMP2). The healing response was
examined in four groups (suture only, acellular scaffold, cellular scaffold, and
cellular BMP2 scaffold) using histologic, bone morphology, and biomechanical
outcomes at 14, 28, and 56 days. Histologically, the healing interface was
dominated by a fibrovascular scar response in all groups. The acellular scaffold
group showed a delayed healing response compared to the other groups. When
examining bone morphology parameters, bone loss was evident in the cellular BMP2
group compared to other groups at 28 days. When examining repair-site mechanical
properties, strength and modulus were decreased in the cellular BMP2 groups
compared to other groups at 28 and 56 days. These results indicated that tendon
to-bone healing in this animal model was dominated by scar formation, preventing
any positive effects of the implanted biomimetic scaffold. Furthermore, cells
transduced with the osteogenic factor BMP2 led to impaired healing, suggesting
that this growth factor should not be used in the tendon-to-bone repair setting.
PMID- 26414601
TI - A Novel Bone Marrow Stimulation Technique Augmented by Administration of
Ultrapurified Alginate Gel Enhances Osteochondral Repair in a Rabbit Model.
AB - Cartilage injuries are a common health problem resulting in the loss of daily
activities. Bone marrow stimulation technique, one of the surgical techniques for
the cartilage injuries, is characterized by technical simplicity and less
invasiveness. However, it has been shown to result in fibrous or
fibrocartilaginous repair with inferior long-term results. This study focused on
using ultrapurified alginate gel (UPAL gel) as an adjuvant scaffold in
combination with a bone marrow stimulation technique. The objective of this study
was to assess the efficacy of a bone marrow stimulation technique augmented by
UPAL gel in a rabbit osteochondral defect model. To achieve this goal, three
experimental groups were prepared as follows: defects without intervention,
defects treated with a bone marrow stimulation technique, and defects treated
with a bone marrow stimulation technique augmented by UPAL gel. The macroscopic
and histological findings of the defects augmented by UPAL gel improved
significantly more than those of the others at 16 weeks postoperatively. The
combination technique elicited hyaline-like cartilage repair, unlike bone marrow
stimulation technique alone. This combination procedure has the potential of
improving clinical outcomes after use of a bone marrow stimulation technique for
articular cartilage injuries.
PMID- 26414603
TI - The Angelina effect revisited: Exploring a media-related impact on public
awareness.
AB - BACKGROUND: In 2013, Angelina Jolie's double mastectomy and publication of her
personal treatment choice for BRCA1 positivity generated considerable media
attention. To the authors' knowledge, the current study is the first prospective
survey conducted among the general public to measure a quantifiable media-related
effect on public awareness. METHODS: The authors analyzed the changes in the
general public's awareness of reconstructive options in breast cancer among 2
female population-matched cohorts aged 18 to 65 years (1000 participants in each
cohort) before (March 2013; poll 1) and after (June 2013; poll 2) the
announcement of Ms. Jolie's mastectomy in May 2013. RESULTS: There was an
observed increase in public awareness: significantly more women from poll 2 were
aware of reconstructive breast surgery being possible after breast cancer-related
mastectomy, notably with regard to autologous tissue and single-stage
reconstructions. Approximately 20% of the women in poll 2 (205 women) indicated
that media coverage regarding Ms. Jolie affected their interest in breast cancer.
A question that was exclusive to poll 2 revealed a preference for autologous
(66.2%) versus implant-based (8.2%) reconstructions, with the remainder
indicating no preference (25.6%). None of the stratification variables were found
to be associated with the above findings. CONCLUSIONS: To the best of the
authors' knowledge, this is the first prospective study to demonstrate a
statistically significant impact of a celebrity announcement on public awareness
regarding breast cancer treatment. The results underscore the importance of a
media-related impact for professionals in the health care sector, which can serve
as a tipping point for raising awareness and improving knowledge concerning a
specific disease among the general public.
PMID- 26414604
TI - Telomerase Reverse Transcriptase and Peroxisome Proliferator-Activated Receptor
gamma Co-Activator-1alpha Cooperate to Protect Cells from DNA Damage and
Mitochondrial Dysfunction in Vascular Senescence.
AB - Reduced telomere length with increasing age in dividing cells has been implicated
in contributing to the pathologies of human aging, which include cardiovascular
and metabolic disorders, through induction of cellular senescence. Telomere
shortening results from the absence of telomerase, an enzyme required to maintain
telomere length. Telomerase reverse transcriptase (TERT), the protein subunit of
telomerase, is expressed only transiently in a subset of adult somatic cells,
which include stem cells and smooth muscle cells. A recent report from Xiong and
colleagues demonstrates a pivotal role for the transcription co-factor peroxisome
proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) in
maintaining TERT expression and preventing vascular senescence and
atherosclerosis in mice. Ablation of PGC-1alpha reduced TERT expression and
increased DNA damage and reactive oxygen species (ROS), resulting in shortened
telomeres and vascular senescence. In the ApoE(-/-) mouse model of
atherosclerosis, forced expression of PGC-1alpha increased expression of TERT,
extended telomeres, and reversed genomic DNA damage, vascular senescence, and the
development of atherosclerotic plaques. Alpha lipoic acid (ALA) stimulated
expression of PGC-1alpha and TERT and reversed DNA damage, vascular senescence,
and atherosclerosis, similarly to ectopic expression of PGC-1alpha. ALA
stimulated cyclic adenosine monophosphate (cAMP) signaling, which in turn
activated the cAMP response element-binding protein (CREB), a co-factor for PGC
1alpha expression. The possibility that ALA might induce TERT to extend telomeres
in human cells suggests that ALA may be useful in treating atherosclerosis and
other aging-related diseases. However, further investigation is needed to
identify whether ALA induces TERT in human cells, which cell types are
susceptible, and whether such changes have clinical significance.
PMID- 26414605
TI - Pilot scale application of anaerobic baffled reactor for biologically enhanced
primary treatment of raw municipal wastewater.
AB - A four-cell anaerobic baffled reactor (ABR) was operated for two years treating
raw municipal wastewater at ambient water and air temperatures of 12-23 degrees
C and -10 to 35 degrees C, respectively. The 1000-L pilot reactor operated at a
12-h hydraulic residence time and was located in the Headworks building of the
Plum Creek Water Reclamation Authority. The average influent was TSS = 510 +/-
400 mg/L, BOD5 = 320 +/- 80 mg/L and the average removal of TSS and BOD5 was 83
+/- 10% and 47 +/- 15%, respectively. The TSS and BOD removal exceeded that of
conventional primary clarification, with no wasting of the settled solids over
the two-years and stoichiometric production of methane. The estimated energy
content of the biogas produced per unit volume of wastewater treated averaged
0.45 kWh/m(3). The TSS and total COD removal in the first cell averaged 75 +/-
15% and 43 +/- 14%, respectively, but methane production was only 20% of the
total observed for the full ABR. The performance of the ABR relative to the
extent of solids hydrolysis and methane production can be varied by the number of
cells and hydraulic residence time. The anaerobic baffled reactor is an energy
positive technology that can be used for biologically enhanced primary treatment
of raw municipal wastewater in cold climates.
PMID- 26414606
TI - Urinary diversion 2015: controversies and new technologies: Choosing the 'right'
diversion.
PMID- 26414607
TI - Can multiparametric MRI rule in or rule out significant prostate cancer?
AB - PURPOSE OF REVIEW: To show how multiparametric MRI can rule in the presence of
significant prostate cancer (PCa), allowing for magnetic resonance-targeted
biopsies to detect aggressive tumors eligible for immediate treatment and to
evaluate if mp-MRI can rule out significant tumor foci to avoid overdiagnosis and
overtreatment of PCa. RECENT FINDINGS: Diffusion-weighted MRI plays a major role
to detect tumor foci and to rule in significant PCa. A low apparent diffusion
coefficient (ADC) value indicates that high Gleason grade tumors are present.
Conversely, the absence of any suspicious focus or foci with a high apparent
diffusion coefficient value indicates either benign tissue or low-grade tumor
SUMMARY: mp-MRI Multiparametric MRI is a highly accurate filter to detect
aggressive tumors and to avoid detection of insignificant cancer. There is
growing evidence that it may be indicated in any man with an elevated Prostatic
Specific Antigen level before considering whether an immediate biopsy should be
performed or whether a simple follow-up should be the option.
PMID- 26414608
TI - Using multiparametric MRI to 'personalize' biopsy for men.
AB - PURPOSE OF REVIEW: In recent years, multiparametric magnetic resonance imaging
(mpMRI) of the prostate has shown promise as a modality to identify areas of
suspicion within the gland which correlate with cancer location and disease
extent. However, optimal individualization of prostate biopsy using mpMRI relies
on aligning the relative benefits of MRI-targeted approaches with the goals of
biopsy. RECENT FINDINGS: For men with prior negative biopsies, mpMRI allows
improved detection of occult high-grade cancers missed by repeat systematic
biopsy but also has the potential to identify men who will not benefit from
repeat biopsy due to a low likelihood of significant disease. For men with prior
low-grade cancer diagnosis, the addition of MRI-targeted biopsy may identify
those who are poor candidates for active surveillance by detecting high-risk
disease without serial biopsies. For men without prior biopsy, mpMRI and targeted
biopsy may help improve high-grade cancer diagnosis and significantly limit the
detection of low-risk disease. SUMMARY: mpMRI of the prostate is a promising tool
to address many of the shortcomings of traditional systematic prostate biopsy.
Biopsy history plays a critical role in determining how to assess the potential
advantages and disadvantages of prostate mpMRI in the context of each patient.
Although these benefits have been suggested by published clinical outcomes data,
there is a need for prospective validation of mpMRI and MRI-targeted biopsy in
comparison with the current approach of systematic biopsy for all men, to define
new paradigms for prostate cancer detection and risk stratification.
PMID- 26414609
TI - Health-related quality of life with urinary diversion.
AB - PURPOSE OF REVIEW: Patients who undergo radical cystectomy and urinary diversion
experience a lengthy period of postoperative recovery from physical, functional,
social, and emotional challenges that greatly impact health-related quality of
life (HRQoL). These changes affect nearly all patients and must be reviewed in
detail as part of the preoperative consultation. However, quantifying a patient's
risk for altered HRQoL is imprecise, thus complicating the choice for urinary
diversion. RECENT FINDINGS: A recent prospective study observed improved global
health status and physical, role, and social functioning in patients treated with
orthotopic neobladder diversion compared with patients treated with ileal conduit
diversion. In contrast, robotic-assisted radical cystectomy does not improve
patient quality of life (QoL) over open radical cystectomy within the first year
of surgery. Enhanced recovery protocols improve immediate postoperative QoL but
their effect on long-term QoL is uncertain. SUMMARY: There is still a significant
lack of understanding about the QoL between various types of urinary diversions.
Recent and ongoing prospective randomized trials in the radical cystectomy
population may shed light on urinary diversion-specific function and related
effects on HRQoL. Ultimately, well designed, large multicenter prospective
controlled trials comparing functional, social, and emotional outcomes of
continent and incontinent urinary diversion are still needed.
PMID- 26414610
TI - Orthotopic urinary diversion.
AB - PURPOSE OF REVIEW: Orthotopic urinary diversion has been performed for more than
30 years. Although it is considered to be the gold standard form of diversion in
many centers of expertise, however it is uncommonly performed outside these
institutions. The purpose of this article is to review the current indications
and outcomes of orthotopic diversion with a focus on male patients and to explore
potential barriers to wider dissemination of the technique. RECENT FINDINGS:
Approximately 75% of patients undergoing radical cystectomy today are candidates
for orthotopic diversion and in the absence of absolute contraindications, very
few patients chose to undergo an ileal conduit for personal reasons. In a recent
quality of life study, the orthotopic neobladder was better than ileal conduit in
terms of global health status and physical functioning. In a prospective
randomized trial comparing a refluxing versus nonrefluxing neobladder, there was
no difference in renal function after 3 years. There is currently insufficient
evidence to suggest improved perioperative outcomes with the use of minimally
invasive techniques. SUMMARY: There are very few absolute contraindications for
an orthotopic neobladder, which remains the gold standard form of diversion at
many centers of expertise. Surgeon experience and thorough preoperative
counseling with realistic expectations can ensure optimal outcomes and patient
satisfaction.
PMID- 26414612
TI - Is It Time to Stop Paying for Computer-Aided Mammography?
PMID- 26414611
TI - Cofeeding intra- and interspecific transmission of an emerging insect-borne
rickettsial pathogen.
AB - Cat fleas (Ctenocephalides felis) are known as the primary vector and reservoir
of Rickettsia felis, the causative agent of flea-borne spotted fever; however,
field surveys regularly report molecular detection of this infectious agent from
other blood-feeding arthropods. The presence of R. felis in additional arthropods
may be the result of chance consumption of an infectious bloodmeal, but isolation
of viable rickettsiae circulating in the blood of suspected vertebrate reservoirs
has not been demonstrated. Successful transmission of pathogens between actively
blood-feeding arthropods in the absence of a disseminated vertebrate infection
has been verified, referred to as cofeeding transmission. Therefore, the
principal route from systemically infected vertebrates to uninfected arthropods
may not be applicable to the R. felis transmission cycle. Here, we show both
intra- and interspecific transmission of R. felis between cofeeding arthropods on
a vertebrate host. Analyses revealed that infected cat fleas transmitted R. felis
to naive cat fleas and rat fleas (Xenopsylla cheopis) via fleabite on a
nonrickettsemic vertebrate host. Also, cat fleas infected by cofeeding were
infectious to newly emerged uninfected cat fleas in an artificial system.
Furthermore, we utilized a stochastic model to demonstrate that cofeeding is
sufficient to explain the enzootic spread of R. felis amongst populations of the
biological vector. Our results implicate cat fleas in the spread of R. felis
amongst different vectors, and the demonstration of cofeeding transmission of R.
felis through a vertebrate host represents a novel transmission paradigm for
insect-borne Rickettsia and furthers our understanding of this emerging
rickettsiosis.
PMID- 26414613
TI - Why is Rheumatoid Arthritis Mortality Still High Despite the Advent of New
Therapies? Comment on the Article by Widdifield et al.
PMID- 26414614
TI - CD33 modulates TREM2: convergence of Alzheimer loci.
AB - We used a protein quantitative trait analysis in monocytes from 226 individuals
to evaluate cross-talk between Alzheimer loci. The NME8 locus influenced PTK2B
and the CD33 risk allele led to greater TREM2 expression. There was also a
decreased TREM1/TREM2 ratio with a TREM1 risk allele, decreased TREM2 expression
with CD33 suppression and elevated cortical TREM2 mRNA expression with amyloid
pathology.
PMID- 26414615
TI - A direct translaminar inhibitory circuit tunes cortical output.
AB - Anatomical and physiological experiments have outlined a blueprint for the
feedforward flow of activity in cortical circuits: signals are thought to
propagate primarily from the middle cortical layer (layer 4, L4) up to L2/3 and
down to the major cortical output layer (L5). Pharmacological manipulations,
however, have contested this model and have suggested that L4 may not be critical
for sensory responses of neurons in either superficial or deep layers. To address
these conflicting models, we reversibly manipulated L4 activity in awake,
behaving mice using cell type-specific optogenetics. In contrast with both
prevailing models, we found that activity in L4 directly suppressed L5, in part
by activating deep, fast-spiking inhibitory neurons. Our data suggest that the
net effect of L4 activity is to sharpen the spatial representations of L5
neurons. Thus, we establish a previously unknown translaminar inhibitory circuit
in the sensory cortex that acts to enhance the feature selectivity of cortical
output.
PMID- 26414616
TI - A positive-negative mode of population covariation links brain connectivity,
demographics and behavior.
AB - We investigated the relationship between individual subjects' functional
connectomes and 280 behavioral and demographic measures in a single holistic
multivariate analysis relating imaging to non-imaging data from 461 subjects in
the Human Connectome Project. We identified one strong mode of population co
variation: subjects were predominantly spread along a single 'positive-negative'
axis linking lifestyle, demographic and psychometric measures to each other and
to a specific pattern of brain connectivity.
PMID- 26414618
TI - Modeling the predictors of safety behavior in construction workers.
AB - This paper presents a model that quantifies the causal relations among safety
variables (latent variables) and workers' safety behavior (indicator) using
statistical data and hypotheses obtained from construction workers and existing
literatures, respectively. The safety variables that affect workers' safety
behaviors are identified from existing studies and operationalized to measure
their causal relations with the workers' behaviors. The model identifies the
directions and degrees of the effect of every latent variable on the other latent
variables and the indicator. Survey questionnaires were administered to
construction workers in South Korea. Exploratory and confirmatory factor
analyses, Cronbach's alpha and structural equation modeling were performed to
test the causal hypotheses using SPSS 18.0 and AMOS 18.0. This study provides the
theoretical model that predicts construction workers' safety behavior on
construction sites using path diagram and analysis.
PMID- 26414619
TI - Computational Lexical Analysis of the Language Commonly Used to Describe Gout.
AB - OBJECTIVE: To characterize the current language that is used in describing and
defining gout, its symptoms, and its treatment by reviewing recent publications
in rheumatology and determining how word choice may, or may not, be reflective of
recent scientific developments in gout specifically. METHODS: This was a
computational linguistics study, using collocations analyses and concordance
analyses on a database of scientific literature related to gout. The final data
set for analysis included 2,590 articles, all relating to gout and published
between May 2003 and May 2013 and amounting to 12,101,036 tokens (sentence
segments). Analysis was conducted by a team of linguists and social scientists.
RESULTS: Our primary finding is that current disease language in gout is marked
by ambiguity and imprecision, as evidenced by numerous terms that have similar
but distinct meanings, but are nevertheless used interchangeably, therefore
blending the slight but significant distinctions between these words. Whereas
treatment language is characterized by a multitude of terms to describe a
therapeutic mechanism of action, there is a relative void of terms and phrases
used to describe success (treating to target) in gout. CONCLUSION: The data
suggest that the language used to describe gout could be improved and updated. A
transformation from an antiquated and insufficiently descript terminological set
to one that reflects the recent scientific and clinical advancements made in the
category would maximize opportunities for patient and physician understanding.
PMID- 26414620
TI - Evaluation of the predictive capacity of DNA variants associated with straight
hair in Europeans.
AB - DNA-based prediction of hair morphology, defined as straight, curly or wavy hair,
could contribute to an improved description of an unknown offender and allow more
accurate forensic reconstructions of physical appearance in the field of forensic
DNA phenotyping. Differences in scalp hair morphology are significant at the
worldwide scale and within Europe. The only genome-wide association study made to
date revealed the Trichohyalin gene (TCHH) to be significantly associated with
hair morphology in Europeans and reported weaker associations for WNT10A and
FRAS1 genes. We conducted a study that centered on six SNPs located in these
three genes with a sample of 528 individuals from Poland. The predictive capacity
of the candidate DNA variants was evaluated using logistic regression;
classification and regression trees; and neural networks, by applying a 10-fold
cross validation procedure. Additionally, an independent test set of 142 males
from six European populations was used to verify performance of the developed
prediction models. Our study confirmed association of rs11803731 (TCHH),
rs7349332 (WNT10A) and rs1268789 (FRAS1) SNPs with hair morphology. The combined
genotype risk score for straight hair had an odds ratio of 2.7 and these
predictors explained ~ 8.2% of the total variance. The selected three SNPs were
found to predict straight hair with a high sensitivity but low specificity when a
10-fold cross validation procedure was applied and the best results were obtained
using the neural networks approach (AUC=0.688, sensitivity=91.2%,
specificity=23.0%). Application of the neural networks model with 65% probability
threshold on an additional test set gave high sensitivity (81.4%) and improved
specificity (50.0%) with a total of 78.7% correct calls, but a high non
classification rate (66.9%). The combined TTGGGG SNP genotype for rs11803731,
rs7349332, rs1268789 (European frequency=4.5%) of all six straight hair
associated alleles was identified as the best predictor, giving >80% probability
of straight hair. Finally, association testing of 44 SNPs previously identified
to be associated with male pattern baldness revealed a suggestive association
with hair morphology for rs4679955 on 3q25.1. The study results reported provide
the starting point for the development of a predictive test for hair morphology
in Europeans. More studies are now needed to discover additional determinants of
hair morphology to improve the predictive accuracy of this trait in forensic
analysis.
PMID- 26414621
TI - Flexible and Stretchable Gold Microstructures on Extra Soft
Poly(dimethylsiloxane) Substrates.
AB - Stretchable gold microstructures are reliably transferred onto an extra-soft
elastomeric substrate. Several major challenges, including failure-free transfer
and reliable bonding with the substrate, are addressed. The simple and
reproducible fabrication allows extensive study and optimization of the
stretchability of meanders in terms of thickness, geometry, and substrate. The
results provide new insights for designing stretchable electronics and novel
routes for stretchrelated, mechanobiological cell-interface applications.
PMID- 26414617
TI - Regeneration versus scarring in vertebrate appendages and heart.
AB - Injuries to complex human organs, such as the limbs and the heart, result in
pathological conditions, for which we often lack adequate treatments. While
modern regenerative approaches are based on the transplantation of stem cell
derived cells, natural regeneration in lower vertebrates, such as zebrafish and
newts, relies predominantly on the intrinsic plasticity of mature tissues. This
property involves local activation of the remaining material at the site of
injury to promote cell division, cell migration and complete reproduction of the
missing structure. It remains an unresolved question why adult mammals are not
equally competent to reactivate morphogenetic programmes. Although organ
regeneration depends strongly on the proliferative properties of cells in the
injured tissue, it is apparent that various organismic factors, such as
innervation, vascularization, hormones, metabolism and the immune system, can
affect this process. Here, we focus on a correlation between the regenerative
capacity and cellular specialization in the context of functional demands, as
illustrated by appendages and heart in diverse vertebrates. Elucidation of the
differences between homologous regenerative and non-regenerative tissues from
various animal models is essential for understanding the applicability of lessons
learned from the study of regenerative biology to clinical strategies for the
treatment of injured human organs.
PMID- 26414622
TI - Lethal influenza infection: Is a macrophage to blame?
AB - Alveolar macrophages (AMs) are critical for immunity against influenza A virus
(IAV) infection. Depletion, hyporeactivity, and disruption of AM development and
differentiation are all associated with lethal IAV infection. AMs drive the
innate immune response that limits IAV infection. AMs are crucial for steady
state homeostasis of pulmonary surfactant, and in turn surfactant proteins
regulate AMs and participate in host defense against IAV. Known factors that are
necessary for AM function and differentiation in vivo include surfactant
proteins, the growth factor GM-CSF, the hormone receptor PPARgamma, and the
transcription factors PU.1 and Bach2. Although PU.1 and PPARgamma are downstream
effectors of GM-CSF, Bach2 works independently. GM-CSF and Bach2-deficient AMs
have phenotypes with immature or alternatively activated states of
differentiation, respectively, and both extremes are unsuitable for surfactant
homeostasis. The activation state of AMs and the local microenvironment may
determine the development of symptomatic versus asymptomatic IAV infection in
different individuals.
PMID- 26414623
TI - Awareness of distractors is necessary to generate a strategy to avoid responding
to them: A commentary on Lin and Murray (2015).
AB - Lin and Murray published in the 2015 January Issue of Psychological Science a
study that claims to have made the surprising discovery of unconscious effects
that are stronger than equivalent conscious effects. Specifically, the authors
claim to have uncovered dissociable components of aware and unaware orienting and
inhibition in exogenous cueing. They suggest an awareness-dependent location
based inhibition mechanism referred to as a negative attentional aftereffect.
Here we argue for a simpler explanation, based on established literature, that
all they have shown is response inhibition to a consciously perceived cue
presented at a fixed location.
PMID- 26414624
TI - Rediscovering the wound hematoma as a site of hemostasis during major arterial
hemorrhage.
AB - BACKGROUND: Treatments for major internal bleeding after injury include
permissive hypotension to decrease the rate of blood loss, intravenous infusion
of plasma or clotting factors to improve clot formation, and rapid surgical
hemostasis or arterial embolization to control bleeding vessels. Yet, little is
known regarding major internal arterial hemostasis, or how these commonly used
treatments might influence hemostasis. OBJECTIVES: (i) To use a swine model of
femoral artery bleeding to understand the perivascular hemostatic response to
contained arterial hemorrhage. (ii) To directly confirm the association between
hemodynamics and bleeding velocity. (iii) To observe the feasibility of
delivering an activated clotting factor directly to internal sites of bleeding
using a simplified angiographic approach. METHODS: Ultrasound was used to measure
bleeding velocity and in vivo clot formation by elastography in a swine model of
contained femoral artery bleeding with fluid resuscitation. A swine model of
internal pelvic and axillary artery hemorrhage was also used to demonstrate the
feasibility of local delivery of an activated clotting factor. RESULTS: In this
model, clots formed slowly within the peri-wound hematoma, but eventually
contained the bleeding. Central hemodynamics correlated positively with bleeding
velocity. Infusion of recombinant human activated factor VII into the injured
artery near the site of major internal hemorrhage in the pelvis and axillae was
feasible. CONCLUSIONS: We rediscovered that clot formation within the peri-wound
hematoma is an integral component of hemostasis and a feasible target for the
treatment of major internal bleeding using activated clotting factors delivered
using a simplified angiographic approach.
PMID- 26414625
TI - Sleep quality but not sleep quantity effects on cortisol responses to acute
psychosocial stress.
AB - Given the well-documented deleterious health effects, poor sleep has become a
serious public health concern and increasing efforts are directed toward
understanding underlying pathways. One potential mechanism may be stress and its
biological correlates; however, studies investigating the effects of poor sleep
on a body's capacity to deal with challenges are lacking. The current study thus
aimed at testing the effects of sleep quality and quantity on cortisol responses
to acute psychosocial stress. A total of 73 college-aged adults (44 females) were
investigated. Self-reported sleep behavior was assessed via the Pittsburgh Sleep
Quality Index and salivary cortisol responses to the Trier Social Stress Test
were measured. In terms of sleep quality, we found a significant three-way
interaction, such that relative to bad sleep quality, men who reported fairly
good or very good sleep quality showed blunted or exaggerated cortisol responses,
respectively, while women's stress responses were less dependent on their self
reported sleep quality. Contrarily, average sleep duration did not appear to
impact cortisol stress responses. Lastly, participants who reported daytime
dysfunctions (i.e. having trouble staying awake or keeping up enthusiasm) also
showed a trend to blunted cortisol stress responses compared to participants who
did not experience these types of daytime dysfunctions. Overall, the current
study suggests gender-specific stress reactivity dysfunctions as one mechanism
linking poor sleep with detrimental physical health outcomes. Furthermore, the
observed differential sleep effects may indicate that while the body may be
unable to maintain normal hypothalamic-pituitary-adrenal functioning in an acute
psychosocial stress situation after falling prey to low sleep quality, it may
retain capacities to deal with challenges during extended times of sleep
deprivation.
PMID- 26414626
TI - Combination of motherwort injection and oxytocin for the prevention of postpartum
hemorrhage after cesarean section.
AB - OBJECTIVE: To evaluate the efficacy and safety of motherwort injection combined
with oxytocin for preventing postpartum hemorrhage (PPH) after cesarean section
(CS). METHODS: From March 2011 and February 2013, a randomized study was
conducted on 165 primipara undergoing CS. 83 and 82 cases were placed into the
combination of oxytocin and motherwort group and oxytocin group, respectively.
Blood loss was calculated and measured during three periods: from placental
delivery to the end of CS, from the end of CS to 2 h postpartum and from 2 h
postpartum to 24 h postpartum. Vital signs were also measured. RESULTS: Blood
loss in the period from placental delivery to the end of CS was similar (P =
0.58) in these two arms. The quantity of total blood loss from the end of CS to 2
h postpartum (P = 0.03) and from 2 h postpartum to 24 h postpartum (P = 0.01)
were significantly reduced in the combination of oxytocin and motherwort group.
No significant abnormal vital signs were observed. Mild, transient side effects
occurred more often in the combination of oxytocin and motherwort group.
CONCLUSIONS: It is efficacious and safe that combination use of motherwort
injection and oxytocin could reduce blood loss and prevent PPH after CS.
PMID- 26414627
TI - Biodistribution of Infused Human Umbilical Cord Blood Cells in Alzheimer's
Disease-Like Murine Model.
AB - Human umbilical cord blood cells (HUCBCs), a prolific source of non-embryonic or
adult stem cells, have emerged as effective and relatively safe immunomodulators
and neuroprotectors, reducing behavioral impairment in animal models of
Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis,
traumatic brain injury, spinal cord injury, and stroke. In this report, we
followed the bioavailability of HUCBCs in AD-like transgenic PSAPP mice and
nontransgenic Sprague-Dawley rats. HUCBCs were injected into tail veins of mice
or rats at a single dose of 1 * 10(6) or 2.2 * 10(6) cells, respectively, prior
to harvesting of tissues at 24 h, 7 days, and 30 days after injection. For
determination of HUCBC distribution, tissues from both species were subjected to
total DNA isolation and polymerase chain reaction (PCR) amplification of the gene
for human glycerol-3-phosphate dehydrogenase. Our results show a relatively
similar biodistribution and retention of HUCBCs in both mouse and rat organs.
HUCBCs were broadly detected both in the brain and several peripheral organs,
including the liver, kidney, and bone marrow, of both species, starting within 7
days and continuing up to 30 days posttransplantation. No HUCBCs were recovered
in the peripheral circulation, even at 24 h posttransplantation. Therefore,
HUCBCs reach several tissues including the brain following a single intravenous
treatment, suggesting that this route can be a viable method of administration of
these cells for the treatment of neurodegenerative diseases.
PMID- 26414628
TI - The Association of Glucose Metabolism and Eigenvector Centrality in Alzheimer's
Disease.
AB - Both fluorine-18-labeled fluorodeoxyglucose ([(18)F]FDG) positron emission
tomography, examining glucose metabolism, and resting-state functional magnetic
resonance imaging (rs-fMRI), using covarying blood oxygen levels, can be used to
explore neuronal dysfunction in Alzheimer's disease (AD). Both measures are
reported to identify similar brain regions affected in AD patients. The spatial
overlap and association of [(18)F]FDG with rs-fMRI in AD patients and controls
were examined to investigate whether these two measures are associated, and if
so, to what extent. For 24 AD patients and 18 controls, [(18)F]FDG and rs-fMRI
data were available. [(18)F]FDG standardized uptake value ratios (SUVr), with
cerebellar gray matter (GM) as reference tissue, were calculated. Eigenvector
centrality (EC) mapping was used to spatially analyze the functional brain
network. Group differences were calculated for [(18)F]FDG and eigenvector
centrality mapping (ECM) values in four cortical regions (occipital, parietal,
frontal, and temporal) and across voxels, with age, gender, and GM as covariates.
Correlation of [(18)F]FDG with ECM was calculated within groups. Both lowered
[(18)F]FDG SUVr and EC values were seen in the parietal and occipital cortex of
AD patients. However, [(18)F]FDG yielded more robust and widespread brain areas
affected in AD patients; hypometabolism was also observed in the temporal cortex
and regions within frontal brain areas. Poor spatial overlap of both measures was
observed. No associations were found between local [(18)F]FDG SUVr and ECM. In
conclusion, agreement of [(18)F]FDG and ECM in AD patients seems moderate at
best. [(18)F]FDG was most accurate in distinguishing AD patients from controls.
PMID- 26414629
TI - A Propensity Score Analysis of the Impact of Invasive Intracranial Pressure
Monitoring on Outcomes after Severe Traumatic Brain Injury.
AB - Although a recent clinical trial (BEST TRIP) demonstrated no improvement in
outcomes with invasive intracranial pressure (ICP) monitoring (ICPM) following
severe traumatic brain injury (TBI), its generalizability has been called into
question. In several global settings ICPM is not the standard of care and is used
at the discretion of the attending neurosurgeon. Our objective was to determine
the impact of ICPM on mortality and 6-month functional outcomes following severe
TBI. The setting was a referral trauma center with 36 intensive care unit (ICU)
beds and 300-600 TBI admissions per year. During a 2-year period data were
prospectively entered into a severe TBI registry. Patients with severe TBI aged
>12 years meeting Brain Trauma Foundation (BTF) criteria for ICPM were included
in the study. Outcomes of interest were in-hospital mortality and poor 6-month
functional outcome defined as Glasgow Outcome Scale (GOS) score of 3 or lower. A
propensity score based analysis incorporating known predictors of outcome in TBI
was utilized to examine the impact of ICPM on outcomes. Of 1345 patients meeting
study criteria 497 (37%) underwent ICPM. In-hospital mortality was 35%
(471/1345). Of 454 patients for whom 6-month outcome was available, 161 (35%)
suffered a poor functional outcome. Following propensity score analysis ICPM use
was associated with an 8% (p = 0.002) decrease in mortality but no significant
effect (p = 0.2) on functional outcome. The use of ICPM following severe TBI was
associated with decreased in-hospital mortality. Further clinical trials of ICPM
in TBI may be warranted.
PMID- 26414630
TI - Anomalous Left Coronary Artery From the Pulmonary Artery in Infants and Toddlers
Misdiagnosed as Myocarditis.
AB - OBJECTIVES: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is
a rare congenital heart defect. Children with this anomaly are usually
asymptomatic at birth and develop symptoms later on in life, which may mimic
myocarditis. We sought to delineate clinical, laboratory, and epidemiological
aspects of this anomaly. METHODS: A retrospective analysis of children with
ALCAPA evaluated in a tertiary medical center in southern Israel was performed. A
computerized search for all patients with the diagnosis of ALCAPA between 2000
and 2011 was performed. The medical records were reviewed; demographic, clinical,
and laboratory data were extracted. RESULTS: A total of 9 patients were included.
In 4 patients, acute deterioration required evaluation in the pediatric emergency
medicine department; in all 4, the initial clinical suspicion was myocarditis.
Failure to thrive was recorded in 7 (77.7%) of the 9 patients and asthma or
wheezing were recorded in 5 (55.5%) of the 9 patients. Normal heart size was
recorded in 4 (44.4%) of the 9 patients. Electrocardiographic abnormalities were
present in all of the patients (100%). A total of 141,675 births were recorded
during the study period, giving an incidence of at least 1 case (0.00635%) per
15,741 births. CONCLUSIONS: Children evaluated in the emergency medicine
department with suspected myocarditis should be evaluated specifically for
ALCAPA. The clinical findings that should raise the suspicion of this anomaly are
failure to thrive and either a diagnosis of asthma or recurrent wheezing.
PMID- 26414631
TI - Persistent Pneumonia: Time to Take a Closer Look.
AB - Primary pulmonary tumors are rare in pediatrics. When they are encountered, they
are usually carcinoid tumors or mucoepidermoid carcinomas. We present a patient
who presented to both his primary care physician and the pediatric emergency
department with recurrent bouts of wheezing and pneumonia, none of which ever
completely resolved despite appropriate treatment. The patient had multiple chest
films, which demonstrated the persistence of what appeared to be a right-sided
infiltrate/atelectasis. Ultimately, the patient underwent a diagnostic workup
that included a computed tomography scan and bronchoscopy. These studies revealed
the presence of a bronchial mucoepidermoid carcinoma. The patient was
successfully treated with photoablation of the lesion through the involvement of
multiple subspecialists, including pediatric pulmonology, pediatric surgery,
pediatric otolaryngology, and pediatric oncology. We discuss the incidence and
epidemiology of pediatric bronchial tumors in general and mucoepidermoid
carcinoma in particular as well as diagnosis, treatment options, and prognosis.
Emergency physicians must maintain a high index of suspicion for alternate
diagnoses in patients whose disease fails to respond to traditionally accepted
therapy.
PMID- 26414632
TI - Idiopathic Pulmonary Hemosiderosis Presenting as Anemia, Failure to Thrive, and
Jaundice in a Toddler.
AB - Idiopathic pulmonary hemosiderosis (IPH) is a rare disease characterized by the
triad of hemoptysis, pulmonary infiltrates on chest radiograph, and anemia. Its
diagnosis should be considered in any child presenting with moderate to severe
anemia and failure to thrive of unclear etiology. Consideration of the
differential diagnosis in such a child should include the review of both
extravascular and intravascular causes of hemolysis. Systemic treatment of IPH
with glucocorticoids has been shown to decrease morbidity, mortality, and disease
progression to pulmonary fibrosis. Thus, diagnostic delays can impact prognosis.
Here, we present a case of a 15-month-old boy with IPH who presented with anemia,
jaundice, and failure to thrive, as well as a history of hemoptysis that was not
initially elicited.
PMID- 26414633
TI - Preliminary Report-The Long Leg Cast With a Pelvic Band: A Novel Approach to
Treatment of Pediatric Femur Fractures.
AB - OBJECTIVES: The aim of the study was to describe the long leg cast with a pelvic
band (LLCPB), a novel alternative to spica casting for treating femur fractures
in patients aged 6 months to 6 years which requires no casting above the waist,
allows for hip flexion adjustments after it is applied, and does not require an
operating room for placement. METHODS: Seven children aged 7.9 months to 3.7
years with femur fractures treated with the LLCPB at a single institution were
retrospectively studied. All children were casted in the emergency department
under conscious sedation. Radiographic and subjective outcomes were recorded.
RESULTS: All 7 children achieved acceptable reduction of their fractures without
the need for re-reduction or cast wedging. Five of the 7 children were discharged
from the emergency department; 1 child required 1 night of hospitalization and
another child required 2 nights of hospitalization. There were no complications.
The cost of placing an LLCPB at our institution was $430.46. The cost of placing
a spica cast in the operating room was $5427.54 to $6465.00. CONCLUSIONS: The
long leg cast with a pelvic band seems to be an acceptable treatment for children
aged 8 months to 4 years with spiral femur fractures. This technique has
significant advantages over traditional and modified spica casts including
allowing for uninhibited toileting, weight bearing on the unaffected leg,
adjustment of hip flexion at any point after placement, and easier access to the
perineum, abdomen, and chest for hygienic and medical purposes. Furthermore,
treatment with an LLCPB presents significant potential for cost savings.
PMID- 26414634
TI - An Assessment of Newly Identified Barriers to and Enablers for Prehospital
Pediatric Pain Management.
AB - OBJECTIVES: The aim of this study was to quantitatively assess the prevalence of
newly identified barriers and enablers to prehospital narcotic analgesic
administration in a sample of paramedics and determine whether these barriers and
enablers differ between new and experienced paramedics. METHODS: We surveyed a
convenience sample of paramedics from urban, suburban, and rural practice
settings in an emergency medical services system. Descriptive statistics were
calculated to describe responses, and differences between new (<=5 years) and
experienced (>5 years) providers were assessed. RESULTS: There were 127 surveys
analyzed; 67% of our sample was experienced and 86% considered treating pain
important. Notable barriers for analgesic administration include causing more
pain from intravenous catheter insertion, parental influences, difficulty
assessing pain, and worry about allergic reactions. Notable enablers include
belief that analgesic administration is important, education to administer
analgesics, and support from agency leadership. There were statistically
significant differences between new and experienced providers in the distribution
of responses for survey items regarding how the importance of treating pain in
children was learned, overall comfort with pediatric patients, receiving negative
responses from superiors about giving pediatric patients analgesics, and
usefulness of the Broselow tape for dosing fentanyl for children. Other barriers
and enablers were not significantly different between new and experienced
providers. CONCLUSIONS: Top barriers to prehospital pediatric analgesic
administration are related to skills and knowledge deficits, whereas enablers
include support from agency leadership and personal views on analgesics. This
information can be used to guide interventions to improve the management of pain
in children.
PMID- 26414635
TI - Mental Health Screening Among Adolescents and Young Adults in the Emergency
Department.
AB - OBJECTIVE: To determine if a new, non-validated mental health screener can detect
the prevalence of alcohol/drug abuse, traumatic exposure, and behavioral symptoms
in adolescents and young adults seeking care in a pediatric emergency department
(ED) for medical complaints. METHODS: An 11-item mental health screener
(Emergency Department Distress Response Screener [ED-DRS] investigator developed)
was created. Patients 12 years or older seen for medical complaints were assessed
by physicians using the ED-DRS. Data were analyzed using the Kuder-Richardson
Formula 20, chi test, Mann-Whitney U test, and Spearman correlation. RESULTS:
Among 992 ED patients, mean age was 15.11 +/- 2.10 years (46.2% boys; 53.8%
girls). Approximately 77.9% were Hispanic/Latino. Symptomatic patients (S)
answered "yes" to at least 1 ED-DRS item; asymptomatic patients answered "no" to
all items. The S patients comprised 47.5% of the sample; asymptomatic patients
comprised 52.5%. Among S patients, alcohol/drug abuse frequency was 14%. The
traumatic exposure frequencies included: 33.5% physically or emotionally
traumatized, 29.3% bullied, 21.2% physically abused, 8.1% touched inappropriately
and 7.0% exposed to domestic violence. Behavioral symptom frequencies included:
33.8% depressed mood, 30.4% anxiety, 23.8% high energy behavior, 6.6%
hallucinations, and 6.2% suicidal/homicidal ideation. CONCLUSIONS: Although
patients present to the ED with medical complaints, they may be at risk for
concomitant mental health problems potentially discoverable using the ED-DRS.
PMID- 26414636
TI - Afebrile Infants Evaluated in the Emergency Department for Serious Bacterial
Infection.
AB - OBJECTIVES: Afebrile infants 0 to 60 days of age are sometimes evaluated for
serious bacterial infection (SBI). Our objective was to describe the clinical and
laboratory findings in this population and compare them to their febrile
counterparts. METHODS: We performed a retrospective observational study comparing
afebrile infants undergoing an SBI evaluation to those evaluated for fever.
RESULTS: We included infants who were admitted to the hospital and had at least 2
of 3 following bacterial cultures: blood, urine, or cerebrospinal fluid. Of the
1184 infants presenting to the emergency department with chief complaints that
may prompt an SBI evaluation, 579 patients met our inclusion criteria with 362 in
the fever group and 217 in the afebrile group. The most common chief complaints
in the afebrile group were respiratory symptoms (27%), seizure (22%),
vomiting/diarrhea (21%), and apparent life-threatening event (11%). Rates of true
positive blood, urine, and cerebrospinal fluid cultures were 2%, 2.4%, and 0.9%
respectively. All cases of bacterial meningitis were in the fever group
antibiotics (P = 0.16). Infants with fever were more likely to receive
antibiotics (P < 0.001), although there were no statistical differences between
the 2 groups in the rates of positive blood or urine cultures. CONCLUSIONS:
Afebrile infants make up a significant percentage of SBI evaluations in the
emergency department. Respiratory symptoms, vomiting, and seizure-like activity
are common presentations. Although rates of bacteremia and urinary tract
infection are higher in the febrile group, this did not reach statistical
significance, and therefore afebrile infants should still be considered at risk
for SBI.
PMID- 26414637
TI - Pelvic Fracture Urethral Injuries in Children: A Case Report and Appraisal of
Their Emergency Management.
AB - Pelvic fracture urethral injuries are uncommon injuries that are frequently
overlooked in the emergency department. We present a case of a 2-year-old girl
whose urethral trauma was initially missed and potentially worsened by the
placement of a urinary catheter. The clinical and diagnostic features of these
rare injuries are discussed along with the controversies surrounding urinary
catheter placement and retrograde urethrography.
PMID- 26414638
TI - SimBaby Plus Standardized Patient Teaching Model in the Teaching of Cases of
Acute and Severe Bronchopneumonia in Infancy.
AB - OBJECTIVE: The aim of the study was to evaluate the effectiveness of SimBaby plus
standardized patient (SP) teaching model in the simulation teaching of acute and
severe bronchopneumonia in infancy. METHODS: A total of 40 students majoring in
clinical medicine were assigned to either group A (SimBaby group, n = 20) or
group B (SP + SimBaby group, n = 20). Medical students' expertise and their
ability to apply the expertise on acute and severe bronchopneumonia in infancy
were assessed using a scoring method, and the impact of the teaching model of
SimBaby plus SP on medical students' comprehensive clinical capacity was assessed
using a questionnaire. RESULTS: The SimBaby plus SP teaching model resulted in
medical students' improvement in mastery and application of the knowledge on
diagnostic accuracy, airway management, endotracheal intubation, and cardiac
massage, enhancement of learning interest, learning initiative, and enthusiasm,
as well as abilities in assessment of information, meta-analysis, linguistic
organization and expression, communication, and clinical thinking. CONCLUSIONS:
The SimBaby plus SP teaching model provided students with a real simulation-based
teaching case of "interrogation-physical examination-operating practices"
achieving satisfactory teaching outcome and also provided a reference case
example for clinical teaching of other pediatric diseases.
PMID- 26414639
TI - Leukemoid Reaction in a Pediatric Patient With Diabetic Ketoacidosis.
AB - Herein, we report a case of a 12-year-old girl who presented with diabetic
ketoacidosis and a leukemoid reaction. Although this association has been
described in a few adult patients, pediatric cases have not been reported. A
leukemoid reaction is commonly defined as an elevation in the white blood cell
count greater than 50,000/MUL in response to severe illness or stress other than
hematologic malignancy; it is considered to be mediated by various hormones,
cytokines, and factors that are released in response to inciting triggers, such
as acidosis. As highlighted in our report, distinguishing a benign leukemoid
reaction from a hematologic malignancy and even tumor lysis syndrome,
particularly in a setting of diabetic ketoacidosis, is crucial to ensuring safe
and efficacious therapeutic interventions.
PMID- 26414640
TI - Case-Control Study of Injury Intervention for Preschool Children in Henggang,
Shenzhen.
AB - AIM: To explore effective interventions for child accidental injury prevention
and to reduce the incidence of injury. METHODS: Cluster random sampling method
was adopted, and children in 19 kindergartens in Henggang, Shenzhen and their
parents were selected as the objects of study. Nineteen kindergartens were
randomly divided into intervention group and control group to carry out the
injury intervention case-control study. RESULTS: Through a series of
interventions, there were certain effects. After the end of the project, the
injury incidence rates of the intervention group and the control group were
4.91%, 10.64%, and the difference was significant; the average costs of treatment
for injuries of the intervention group and the control group were 168.4 Yuan and
206.8 Yuan, and the difference was statistically significant; compared with
before the implementation of the project, the rate of various types of injuries
after the end of the project declined, in which, the rate of mechanical injury,
pet bites, accidental falls, burns, and traffic accidents decreased
significantly. The differences were significant. CONCLUSIONS: Injury
interventions can effectively prevent and control the occurrence of injury.
PMID- 26414641
TI - A Survey of Attitudes and Practices Regarding the Use of Steroid Supplementation
in Pediatric Sepsis.
AB - OBJECTIVE: Although corticosteroid (CS) supplementation for pediatric septic
shock (PSS) is recommended by American College of Critical Care Medicine sepsis
guidelines, most data are based on adult trials. Standardized protocols for
stimulation testing for adrenal insufficiency (AI) and CS treatment in children
have been reported, but the current state of CS use and protocols have not been
evaluated in pediatric intensive care units in the United States. We surveyed a
group of pediatric intensivists to assess current approaches. DESIGN: An
electronic survey with 54 questions on attitudes and current use of CSs was
distributed to 49 pediatric critical care and 49 pediatric endocrinology
fellowship program directors. MAIN RESULTS: Twenty-one (43%) of 49 critical care
recipients completed the survey. Eleven (52%) were from medical/surgical units
and 10 (48%) were from medical/surgical/cardiac units, with a median of 24 beds
and 1614 annual admissions. Thirteen (62%) of 21 recipients rated the importance
of steroids in the management of PSS as greater than 4 or 5, with 1 being of no
importance and 5 of critical importance. Nineteen (90%) of 21 recipients thought
AI occurs "sometimes" or "often" in septic shock. Adrenocorticotropin stimulation
testing was frequently used (19 of 21; 90%) but not in protocol. Eighteen (85%)
of 21 recipients agreed that "some should" receive "steroids as it improves
outcome" and 9% agreed that "most should..." Fourteen (66%) of 21 recipients
reported that more than 50% of patients with vasopressor-refractory PSS receive
CSs. Hydrocortisone was used in 21 (100%) of 21 recipients, but dosing and
duration were variable. Concerns to limit/avoid CSs included hyperglycemia (38%),
superinfections (81%), and critical illness myopathy (57%). Only 3 (14%) of 21
recipients reported that they used a CS protocol for PSS. Sixteen (76%) of 21
recipients were not comfortable drawing conclusions from adult studies for PSS.
Nineteen (90%) of 21 recipients agreed that it would be important to perform a
randomized trial for CS use in PSS. CONCLUSIONS: Corticosteroids are used at most
centers for treatment of PSS, but significant variation in attitudes and use
exists. Most centers identify AI as frequent; most report variable use of
stimulation testing and dosing of CSs. Few centers currently use a standard
protocol for diagnosis and treatment. Interest in performing a randomized trial
for CSs remains because in part of reluctance to accept adult trial data.
PMID- 26414642
TI - Factors Associated With Orthopedic Aftercare in a Publicly Insured Pediatric
Emergency Department Population.
AB - OBJECTIVES: Children with public insurance are less likely than children with
private insurance to obtain follow-up care after emergency department (ED) care.
This study aimed to determine if specific demographic and clinical factors are
associated with aftercare compliance in a population of publicly insured
pediatric ED patients with orthopedic injuries. METHODS: This was a retrospective
case-control study of Washington, DC, children aged 0 to 17 years with public
insurance discharged with isolated forearm fractures from the Children's National
Medical Center ED from 2003 to 2006. Bivariable analyses and multivariable
logistic regression were performed to measure the association between
sociodemographic variables and failure to follow up. RESULTS: Six hundred
children met the inclusion criteria. The overall cohort was 63.7% male and 81.7%
African American, with a mean age of 8.8 (SE, 0.2) years. Overall, 85.7% of
patients went to a follow-up orthopedic appointment, and 68.2% of patients had
timely orthopedic follow-up, defined as 14 days or less after discharge from the
ED. Treatment with orthopedic reduction (adjusted odds ratio [OR], 2.0 [1.33
2.93]) was positively associated with timely orthopedic follow-up, whereas older
age (adjusted OR, 0.9 [0.88-0.97]) was significantly associated with failure to
follow up. In the subset of patients who required orthopedic reduction in the ED,
older age was significantly associated with failure to follow up (adjusted OR,
0.80 [0.74-0.94]). CONCLUSIONS: Mild fracture severity is associated with lack of
orthopedic follow-up for patients with public insurance. Older age was associated
with lack of follow-up, even in the subgroup with severe fractures. Targeted
interventions to improve orthopedic aftercare compliance should focus on older
patients with severe forearm fractures.
PMID- 26414643
TI - MicroRNA-498 Inhibition Enhances the Differentiation of Human Adipose-Derived
Mesenchymal Stem Cells into Podocyte-Like Cells.
AB - Podocyte depletion is a key event in the progression of end-stage kidney disease
(ESKD) resulting in nephrotic proteinuria and renal failure, but the treatment
options are limited to dialysis and renal transplantation. So there is an urgent
need for renal regenerative therapies. Generation of podocytes from human stem
cells is regarded as a promising therapeutic strategy to repair or regenerate the
damaged kidneys; however, the reliable induction system remains a challenge. In
this study, we established a two-stage induction protocol for podocyte generation
from human adipose-derived mesenchymal stem cells (hAD-MSCs). We initially
established a condition that induces hAD-MSCs toward intermediate mesoderm cells
with activin A and high concentration of retinoic acid (RA). Subsequently, by
using the combination of activin A and low concentration of RA and BMP7, we
generated podocyte-like cells expressing multiple podocyte-specific markers and
able to integrate into a developing nephron of embryonic kidney explant culture
and ameliorate proteinuria and kidney injure in adriamycin-treated mice.
Furthermore, we identified that miRNA-498 inhibitor has potential to improve the
differentiation of hAD-MSCs into podocyte-like cells and established a robust
induction protocol. Thereby, our study advocated an efficient method for the
induction of kidney podocyte-like (iPod) cells from hAD-MSCs and provided an
ideal candidate for regenerative therapies of the kidney.
PMID- 26414644
TI - Radiofrequency ablation of hepatocellular carcinoma: Mono or multipolar?
AB - BACKGROUND AND AIMS: Thermo-ablation by radiofrequency is recognized as a
curative treatment for early-stage hepatocellular carcinoma. However, local
recurrence may occur because of incomplete peripheral tumor destruction.
Multipolar radiofrequency has been developed to increase the size of the maximal
ablation zone. We aimed to compare the efficacy of monopolar and multipolar
radiofrequency for the treatment of hepatocellular carcinoma and determine
factors predicting failure. METHODS: A total of 171 consecutive patients with 214
hepatocellular carcinomas were retrospectively included. One hundred fifty-eight
tumors were treated with an expandable monopolar electrode and 56 with a
multipolar technique using several linear bipolar electrodes. Imaging studies at
6 weeks after treatment, then every 3 months, assessed local effectiveness.
Radiofrequency failure was defined as persistent residual tumor after two
sessions (primary radiofrequency failure) or local tumor recurrence during follow
up. This study received institutional review board approval (number 2014/77).
RESULTS: Imaging showed complete tumor ablation in 207 of 214 lesions after the
first session of radiofrequency. After a second session, only two cases of
residual viable tumor were observed. During follow-up, there were 46 local tumor
recurrences. Thus, radiofrequency failure occurred in 48/214 (22.4%) cases. By
multivariate analysis, technique (P < 0.001) and tumor size (P = 0.023) were
independent predictors of radiofrequency failure. Failure rate was lower with the
multipolar technique for tumors < 25 mm (P = 0.023) and for tumors between 25 and
45 mm (P = 0.082). There was no difference for tumors >= 45 mm (P = 0.552).
CONCLUSIONS: Compared to monopolar radiofrequency, multipolar radiofrequency
improves tumor ablation with a subsequent lower rate of local tumor recurrence.
PMID- 26414645
TI - Post-Transurethral Resection of the Prostate Inflation of Pressure-Controlled
Endorectal Balloon-Impact on Postoperative Bleeding: A Preliminary Experimental
Pilot Study.
AB - OBJECTIVE: To evaluate the impact of rectal balloon (RB) inflation on post
transurethral resection of the prostate (TURP) bleeding in patients with
symptomatic benign prostatic hyperplasia. METHODS: After institutional review
board approval, patients who were eligible for TURP were randomized into two
equal groups, depending on whether they received postoperative endorectal balloon
(RB) (GII) or not (GI). The tip of three-way Foley catheter was fixed to a
balloon by a blaster strip to prepare air-tight RB. Postoperatively, the RB was
inflated for 15 minutes by a pressure-controlled sphygmomanometer. Perioperative
data were compared between both groups, including hemoglobin (Hb) deficit 24-hour
postoperatively and at time of discharge. Functional outcomes, anorectal
complaints, and adverse events were assessed perioperatively and after 1 and 3
months. RESULTS: Fifty patients were enrolled, including 13 (26%) patients who
presented with indwelling urethral catheters. Baseline data and mean resected
tissue weight were comparable between both groups, including preoperative Hb (p =
0.17). Immediate postoperative Hb deficit was, comparable between GI and GII
patients (0.58 +/- 0.18 vs 0.60 +/- 0.2, p = 0.56) before RB inflation,
respectively. However, compared to GI patients, mean Hb deficit significantly
decreased in GII patients 24-hour postoperatively (0.2 +/- 0.2 vs 0.7 +/- 0.3 g,
p = 0.002) and at time of discharge (0.8 +/- 0.2 vs 1.3 +/- 0.4 g, p = 0.003).
GII patients needed significantly less postoperative irrigation (2.1 +/- 1.6 vs
8.3 +/- 1.8 L, p < 0.001), shorter catheterization time (2.3 +/- 0.8 vs 3.8 +/-
1.3 days, p < 0.001), and shorter hospital stay (2.6 +/- 0.5 vs 4.3 +/- 1.0 days,
p < 0.001). Both groups were comparable in all functional outcomes at the most
recent follow-up. Blood transfusion was needed in only one patient (4%) in GI. No
patient needed recystoscopy for hematuria or clot retention in either group,
while there were no anorectal complaints reported by GII patients. CONCLUSIONS:
Post-TURP endorectal balloon inflation seems to be simple, safe, and an efficient
procedure to reduce postoperative bleeding and irrigation volume. It is
significantly associated with shorter catheterization time and hospital stay.
PMID- 26414646
TI - Cerebral venous thrombosis following spinal surgery in a patient with Factor V
Leiden mutation.
AB - Cerebral venous thrombosis is a devastating event leading to high mortality and
morbidity rates. We present a case of cerebral venous thrombosis that occurred
following spinal surgery in a patient with Factor V Leiden mutation and G1691A
heterozygosity. Possible prevention and treatment strategies have been discussed.
PMID- 26414647
TI - Estimation of groundwater recharge via deuterium labelling in the semi-arid
Cuvelai-Etosha Basin, Namibia.
AB - The stable water isotope deuterium ((2)H) was applied as an artificial tracer
((2)H2O) in order to estimate groundwater recharge through the unsaturated zone
and describe soil water movement in a semi-arid region of northern central
Namibia. A particular focus of this study was to assess the spatiotemporal
persistence of the tracer when applied in the field on a small scale under
extreme climatic conditions and to propose a method to obtain estimates of
recharge in data-scarce regions. At two natural sites that differ in vegetation
cover, soil and geology, 500 ml of a 70% (2)H2O solution was irrigated onto water
saturated plots. The displacement of the (2)H peak was analyzed 1 and 10 days
after an artificial rain event of 20 mm as well as after the rainy season.
Results show that it is possible to apply the peak displacement method for the
estimation of groundwater recharge rates in semi-arid environments via deuterium
labelling. Potential recharge for the rainy season 2013/2014 was calculated as 45
mm a(-1) at 5.6 m depth and 40 mm a(-1) at 0.9 m depth at the two studied sites,
respectively. Under saturated conditions, the artificial rain events moved 2.1
and 0.5 m downwards, respectively. The tracer at the deep sand site (site 1) was
found after the rainy season at 5.6 m depth, corresponding to a displacement of
3.2 m. This equals in an average travel velocity of 2.8 cm d(-1) during the rainy
season at the first site. At the second location, the tracer peak was discovered
at 0.9 m depth; displacement was found to be only 0.4 m equalling an average
movement of 0.2 cm d(-1) through the unsaturated zone due to an underlying
calcrete formation. Tracer recovery after one rainy season was found to be as low
as 3.6% at site 1 and 1.9% at site 2. With an in situ measuring technique, a
three-dimensional distribution of (2)H after the rainy season could be measured
and visualized. This study comprises the first application of the peak
displacement method using a deuterium labelling technique for the estimation of
groundwater recharge in semi-arid regions. Deuterium proved to be a suitable
tracer for studies within the soil-vegetation-atmosphere interface. The results
of this study are relevant for the design of labelling experiments in the
unsaturated zone of dry areas using (2)H2O as a tracer and obtaining estimations
of groundwater recharge on a local scale. The presented methodology is
particularly beneficial in data-scarce environments, where recharge pathways and
mechanisms are poorly understood.
PMID- 26414648
TI - Femoral condyle curvature is correlated with knee walking kinematics in
ungulates.
AB - The knee has been the focus of many studies linking mammalian postcranial form
with locomotor behaviors and animal ecology. A more difficult task has been
linking joint morphology with joint kinematics during locomotor tasks. Joint
curvature represents one opportunity to link postcranial morphology with walking
kinematics because joint curvature develops in response to mechanical loading. As
an initial examination of mammalian knee joint curvature, the curvature of the
medial femoral condyle was measured on femora representing 11 ungulate species.
The position of a region of low curvature was measured using a metric termed the
"angle to low curvature". This low-curvature region is important because it
provides the greatest contact area between femoral and tibial condyles. Kinematic
knee angles during walking were derived from the literature and kinematic knee
angles across the gait cycle were correlated with angle to low curvature values.
The highest correlation between kinematic knee angle and the angle to low
curvature metric occurred at 20% of the walking gait cycle. This early portion of
the walking gait cycle is associated with a peak in the vertical ground reaction
force for some mammals. The chondral modeling theory predicts that frequent and
heavy loading of particular regions of a joint surface during ontogeny will
result in these regions being flatter than the surrounding joint surface. The
locations of flatter regions of the femoral condyles of ungulates, and their
association with knee angles used during the early stance phase of walking
provides support for the chondral modeling theory.
PMID- 26414649
TI - Inhibition of Lipid Oxidation in Oil-in-Water Emulsions by Interface-Adsorbed
Myofibrillar Protein.
AB - This study investigated the role of interfacial myofibrillar protein (MFP) in the
oxidative stabilization of meat emulsions. Emulsions with 10% oil were prepared
using either 2% (w/v) Tween 20 or 0.25, 0.5, and 1% (w/v) MFP and then subjected
to hydroxyl radical oxidation at 4 degrees C for 0, 2, and 24 h. MFP was more
readily oxidized (intrinsic fluorescence quenching, sulfur losses, and carbonyl
formation) than oil [conjugated dienes and 2-thiobarbituric acid-reactive
substances (TBARS)]. However, oxidized MFP in the continuous phase stimulated
lipid oxidation after 24 h, sharply contrasting with interface-adsorbed MFP that
inhibited TBARS formation nearly 90% (p < 0.05). Interfacial MFP from 2 h
oxidized samples exhibited greater losses of fluorescence and more extensive
polymerization of myosin (detected by sodium dodecyl sulfate-polyacrylamide gel
electrophoresis) than MFP present in the continuous phase. Results indicated
that, due to the physical localization, interface-adsorbed MFP in general and
myosin in particular provided accentuated protection of emulsions against
oxidation.
PMID- 26414650
TI - Elimination of Granulocytic Myeloid-Derived Suppressor Cells in Lupus-Prone Mice
Linked to Reactive Oxygen Species-Dependent Extracellular Trap Formation.
AB - OBJECTIVE: Emerging evidence supports a crucial role of myeloid-derived
suppressor cells (MDSCs) in the regulation of autoimmune diseases. However, their
role in systemic lupus erythematosus (SLE) remains unknown. This study sought to
address the role of MDSCs in the pathogenesis of SLE. METHODS: MDSCs from (NZB *
NZW)F1 lupus-prone mice were assessed for phenotype by flow cytometry, and the
function of MDSCs was analyzed by in vitro T cell proliferation assay and real
time quantitative polymerase chain reaction. Extracellular trap (ET) formation
was evaluated by immunofluorescence and confocal microscopy. The production of
reactive oxygen species (ROS) by Ly-6G+ cells was determined by fluorescence
activated cell sorting analysis. RESULTS: Expansion of MDSCs was impaired and the
function of MDSCs was defective in the lymphoid organs of (NZB * NZW)F1 lupus
prone mice with established disease, in which involvement of predominantly the
granulocytic MDSC (G-MDSC) cell subset was observed. More specifically, the
results showed that increased elimination of G-MDSCs, driven by the inflammatory
milieu of lupus, could be attributed to ET formation, and that cytokines, such as
interferon-alpha (IFNalpha), IFNgamma, and interleukin-6, play a role in this
process. Induction of ET release by G-MDSCs was mediated by the production of
ROS, since inhibition of ROS generation significantly reduced ET release.
CONCLUSION: Collectively, the results of this study reveal that elimination of a
crucial regulatory immune cell subset is a feature of the SLE microenvironment.
These findings provide new insights into the pathogenetic mechanisms of the
disease.
PMID- 26414651
TI - Electrodiffusiophoresis of a large-zeta-potential particle in weak fields.
AB - The electrodiffusiophoresis of a large-zeta-potential (zeta) particle in weak
fields is investigated. In this large-zeta regime, Debye-layer kinetics
determines O(1) perturbations to the electric- and concentration fields in the
surrounding electroneutral solution. Taking these effects into account, the
expressions of the slip-flow coefficient and the effective surface boundary
conditions for the electric- and concentration fields are derived. For binary and
symmetric electrolyte where only one ion species carries the current in the
electroneutral domain, the far-field salt gradient as related to the electric
field is determined. The electrodiffusiophoretic mobility is obtained for three
particle geometries: sphere, cylinder and spheroid arbitrarily oriented with
respect to the externally applied field. Strong departure from Smoluchowskian
behavior is found. If co-ion is the current carrier, the mobility is independent
of zeta, regardless of the body shape. Also, the hydrodynamic flow-field is
irrotational. If counter-ion is the current carrier, the problem formulated in
terms of a properly-defined scalar field (Omega), which embodies both the
electric potential (Psi) and the salt concentration, becomes formally identical
to the one addressed in our previous work, concerning the small-zeta regime, with
negligible salt gradients. Then, all the results obtained in that study are
extended and applied even to the large-zeta regime considered here, provided the
new expressions now derived for the surface boundary conditions and the slip-flow
coefficient are employed and Omega is used in place of Psi. The present results
are discussed also in comparison with the classical studies of Dukhin et al and
O'Brien et al concerning electrophoresis of highly charged particles with no salt
gradient at infinity, and with recent studies of electrodiffusiophoresis, which,
however, neglected the fields perturbations caused by Debye-layer kinetics. It is
found that the effects addressed and incorporated in the present study determine
remarkably different mobility-versus-zeta behaviour as compared to those previous
theories.
PMID- 26414652
TI - Predictions of bioenhancement of nonaqueous phase liquid ganglia dissolution
using first- and zero-order biokinetic models.
AB - The bioenhanced dissolution of nonaqueous phase liquid (NAPL) contaminants that
occurs as a result of an increased concentration gradient is influenced by
several factors, including the biokinetics. This is important because available
data suggest that at typical NAPL source zone concentrations, descriptions of
dissolution bioenhancement may require kinetic expressions ranging from first- to
zero-order. In this work, an analytical model for the bioenhancement factor, E,
is developed for NAPL ganglia dissolution with zero-order kinetics, and compared
to a model for E with first-order kinetics. The models are analyzed and an
illustrative example is provided to demonstrate the importance of using the
correct biokinetics when estimating the potential magnitude of the bioenhancement
of NAPL ganglia dissolution.
PMID- 26414653
TI - Perioperative blood loss and gastrointestinal tolerability of etoricoxib and
diclofenac in total hip arthroplasty (ETO-DIC study): a single-center,
prospective double-blinded randomized controlled trial.
AB - OBJECTIVE: Non-selective NSAIDs can cause serious gastrointestinal side-effects.
Selective COX-2 blockers are a reasonable alternative for pain treatment. They do
not seem to affect platelet function and consequently cause a lower perioperative
blood loss than non-selective NSAIDs. This study compared etoricoxib and
diclofenac during a perioperative (9 days) period after THA to investigate total
blood loss and gastrointestinal tolerability. The hypothesis was that etoricoxib
is superior to diclofenac. METHODS: A total of 100 patients (50 in each group)
were included in this trial. Etoricoxib (90 mg) was administered once and
diclofenac sodium (75 mg) twice daily for 9 days. Total blood loss during and
after primary cementless THA was detected. The rate of adverse events (AEs) and
serious adverse events (SAEs) was analyzed to detect gastrointestinal
tolerability. RESULTS: The mean total blood loss (calculated) was 1548 +/- SD 468
ml in the etoricoxib (ETO) group and 1649 (SD 547) ml in the diclofenac (DIC)
group. The mean duration of THA was 81 min (SD 29) in the DIC and 75 min (SD 30)
in the ETO group. Hence, the mean calculated total blood loss was 101 ml higher
in the DIC group. This difference was not statistically significant (p = 0.334).
Fifty-six patients (28 in each group) received a cell saver retransfusion, but
only one patient (ETO group) needed an additional red blood cell transfusion. The
hidden blood loss was 1067 ml (SD 603) in the DIC group and 999 ml (SD 378) in
the ETO group. The gastrointestinal tolerability (number of adverse and serious
adverse events) was not significantly different between groups. CONCLUSION: There
was no statistically significant difference in perioperative blood loss after
primary THA under etoricoxib (90 mg) compared to diclofenac (75 mg). Furthermore,
no gastrointestinal superiority of etoricoxib could be detected during a short
period of 9 days.
PMID- 26414654
TI - Chronic Aspects of Pediatric Traumatic Brain Injury: Review of the Literature.
AB - Traumatic brain injury (TBI) in children, while the brain is in a state of rapid
change and development, can adversely impact their development, their extended
environment, and their families. The extant literature has identified several
physiological, genetic, and environmental variables that predict outcomes after
pediatric TBI; nonetheless, the individual course of recovery and later
development of a given child is uniquely shaped by injury-related factors (e.g.,
nature and extent of the injury itself, the developmental status of the child) as
well as a number of personal and family variables (e.g., pre-injury cognitive,
genetic, and psychological status of the child, family functioning and resources,
coping style). Further, the effects of a brain injury during development may or
may not become evident immediately after injury depending on a number of factors.
Instead, observing trajectories of development over time may allow for a better
understanding of the long-term consequences in many functional domains that
interest researchers, clinicians, and families. The current article reviews the
chronic aspects of medical/health, cognitive/academic, emotional/behavioral, and
family/social outcomes after pediatric TBI, with the goal of providing monitoring
and treatment strategies for affected children and their families, as well as
serving as a resource for researchers designing studies to better understand this
heterogeneous population.
PMID- 26414655
TI - Highly Enantioselective Construction of Fluoroalkylated Quaternary Stereocenters
via Organocatalytic Dehydrated Mannich Reaction of Unprotected Hemiaminals with
Ketones.
AB - A general organocatalytic asymmetric dehydrated Mannich reaction of fluoroalkyl
hemiaminals with ketones is reported. In this Mannich reaction, previously less
explored aryl ketones showed great reactivity. By virtue of this efficient
method, a wide range of biologically active beta-amino ketones were directly
obtained. More importantly, two different intermediates involved in the reaction
were detected and identified by (19)F NMR and HRMS analysis. Furthermore, the
synthetic utility of the products was demonstrated by the synthesis of the
biologically active fluoroalkyl beta-amino alcohols.
PMID- 26414656
TI - Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer:
Oncologic and Functional Outcomes from the COLD Registry.
AB - OBJECTIVE: To evaluate the oncological and functional outcomes of primary
cryotherapy in men with clinically localized, high-grade prostate cancer.
SUBJECTS AND METHODS: We included all men with biopsy Gleason score >=8,
localized (cT1-2) disease with a serum prostate-specific antigen (PSA) <=50 ng/mL
from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical
progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2
ng/mL). Secondary outcomes of continence (defined as strictly no leak) and
potency (able to have intercourse) were patient reported. Factors influencing
BPFS were evaluated individually using Kaplan Meier and in a multivariate model
using Cox regression. RESULTS: Altogether, 300 men were included for analysis.
The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months.
Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2%
and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of
men and this tended to occur in men with larger prostates, likely as a technical
consideration for downsizing before cryosurgery. At multivariate analysis, the
presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA
nadir of >=0.4 ng/mL (HR 5.7) were the only significant variables associated with
biochemical progression using Cox regression. Complete continence was noted in
90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence
of rectourethral fistulae and urinary retention requiring intervention beyond
temporary catheterization was 1.3% and 3.3%, respectively. CONCLUSION: Primary
cryotherapy appears to be effective and safe in the community setting for high
grade, clinically localized prostate cancer in the short term.
PMID- 26414657
TI - Lifestyle habits of 12,800 IVF patients: Prevalence of negative lifestyle
behaviors, and impact of region and insurance coverage.
AB - Lifestyle habits of women undergoing in vitro fertilization (IVF) treatment are
largely unknown. Therefore, this prospective study aimed to determine the
prevalence of negative lifestyle habits in women undergoing IVF and determine if
habits are related to the region in the United States and/or by mandated
insurance coverage. A total of 12,811 ART patients were surveyed in infertility
clinics throughout the US. They took an online questionnaire added to the patient
portal of electronic medical record eIVF, a fertility-specific electronic health
record. Of the women surveyed, 17-23% of patients drank alcohol, 2-7% smoked, 62
68% drank caffeine, < 1% used recreational drugs, and 47-62% exercised during
their IVF treatment. There were a few statistically significant regional
differences in health habits (p < 0.001) but there were no differences in health
habits between women who resided in a state with mandated insurance coverage
versus those without insurance coverage. This is the first prospective assessment
of lifestyle habits across regions in the USA and by insurance coverage. The
study concluded that women undergoing IVF engage in behaviors which may
negatively impact their cycle. Women in certain parts of the US had significantly
worse habits than other regions, but the availability of mandated insurance
coverage did not impact health habits.
PMID- 26414658
TI - Antineutrophil Cytoplasmic Antibody-Positive Small-Vessel Vasculitis Associated
with Antithyroid Drug Therapy: How Significant Is the Clinical Problem?
AB - BACKGROUND: The aim of this review was to delineate the characteristics of
antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis
associated with antithyroid drugs (ATD). A PubMed search was made for English
language articles using the search terms antithyroid drugs AND ANCA OR ANCA
associated vasculitis. SUMMARY: The literature includes approximately 260 case
reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of
these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25%
with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA
positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and
0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy
were the main factors contributing to the emergence of ANCA positivity. Before
ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%.
During ATD administration, 20% of patients were found to be positive for ANCA.
Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence
of vasculitis, corresponding to 3% of all patients who received ATD. Clinical
manifestations of ANCA-associated vasculitis related to ATD were extremely
heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by
rapid clinical improvement and a favorable prognosis. CONCLUSIONS: ANCA screening
is not systematically recommended for individuals on ATD therapy, particularly
given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should
be given to the pediatric population with Graves' disease who receive ATD, as
well as patients treated with thiouracil derivatives and those on long-term ATD
therapy.
PMID- 26414659
TI - The antimicrobial activity of mecillinam, nitrofurantoin, temocillin and
fosfomycin and comparative analysis of resistance patterns in a nationwide
collection of ESBL-producing Escherichia coli in Norway 2010-2011.
AB - BACKGROUND: The prevalence of extended-spectrum beta-lactamase (ESBL)-producing
Escherichia coli in Norway has been steadily increasing during the last 10-15
years as part of a global pandemic. ESBL producers frequently express co
resistance to other important antimicrobial drug classes, limiting therapeutic
options. This has led to regained interest in older antimicrobial agents. The aim
of this study was to evaluate the antimicrobial activity of mecillinam,
nitrofurantoin, temocillin and fosfomycin, as well as to perform a comparative
analysis of resistance patterns in a nationwide collection of ESBL-producing E.
coli. METHODS: A nationwide collection of all 105 clinical isolates of ESBL
producing E. coli from the Norwegian Organisation for Surveillance of
Antimicrobial Resistance (NORM) during 2010-2011 was analyzed. Detection and
identification of ESBL-encoding genes were performed by PCR and sequencing for
confirmation of ESBL variants of blaTEM and blaSHV (2010) or microarray (2011).
Minimum inhibitory concentrations (MICs) or MIC correlates were determined using
MIC gradient tests or VITEK 2, respectively. Comparative analysis of resistance
patterns was performed. RESULTS: All isolates were susceptible to fosfomycin,
temocillin (urinary tract breakpoint) and meropenem. For mecillinam and
nitrofurantoin, 6% and 9% of the isolates, respectively, were non-susceptible. A
high level of susceptibility was also observed for amikacin (95%). In contrast,
the non-susceptibility proportions to ampicillin (100%), cefotaxime (97%),
ceftazidime (77%), aztreonam (87%), gentamicin (42%), tobramycin (52%),
ciprofloxacin (76%) and trimethoprim-sulfamethoxazole (71%) were higher.
CONCLUSIONS: Overall, the in vitro susceptibility to nitrofurantoin, fosfomycin,
mecillinam and temocillin was high, indicating that these drugs are good options
for treating uncomplicated urinary tract infections caused by ESBL-producing E.
coli.
PMID- 26414660
TI - Engineering Translational Activators with CRISPR-Cas System.
AB - RNA parts often serve as critical components in genetic engineering. Here we
report a design of translational activators which is composed of an RNA
endoribonuclease (Csy4) and two exchangeable RNA modules. Csy4, a member of Cas
endoribonuclease, cleaves at a specific recognition site; this cleavage releases
a cis-repressive RNA module (crRNA) from the masked ribosome binding site (RBS),
which subsequently allows the downstream translation initiation. Unlike small RNA
as a translational activator, the endoribonuclease-based activator is able to
efficiently unfold the perfect RBS-crRNA pairing. As an exchangeable module, the
crRNA-RBS duplex was forwardly and reversely engineered to modulate the dynamic
range of translational activity. We further showed that Csy4 and its recognition
site, together as a module, can also be replaced by orthogonal endoribonuclease
recognition site homologues. These modularly structured, high-performance
translational activators would endow the programming of gene expression in the
translation level with higher feasibility.
PMID- 26414662
TI - Visualising the problems with balancing lithium-sulfur batteries by "mapping"
internal resistance.
AB - Frequent and continuous determination of battery internal resistance by a simple
current-interrupt method enables the visualisation of cell behaviour through the
creation of resistance "maps", showing changes in resistance as a function of
both capacity and cycle number. This new approach is applied here for the
investigation of cell failure in the lithium-sulfur system with Li electrode
excesses optimised towards practically relevant specifications.
PMID- 26414661
TI - High Fat Diet Enhances beta-Site Cleavage of Amyloid Precursor Protein (APP) via
Promoting beta-Site APP Cleaving Enzyme 1/Adaptor Protein 2/Clathrin Complex
Formation.
AB - Obesity and type 2 diabetes are risk factors of Alzheimer's disease (AD). We
reported that a high fat diet (HFD) promotes amyloid precursor protein (APP)
cleavage by beta-site APP cleaving enzyme 1 (BACE1) without increasing BACE1
levels in APP transgenic mice. However, the detailed mechanism had remained
unclear. Here we demonstrate that HFD promotes BACE1/Adaptor protein-2 (AP
2)/clathrin complex formation by increasing AP-2 levels in APP transgenic mice.
In Swedish APP overexpressing Chinese hamster ovary (CHO) cells as well as in SH
SY5Y cells, overexpression of AP-2 promoted the formation of BACE1/AP-2/clathrin
complex, increasing the level of the soluble form of APP beta (sAPPbeta). On the
other hand, mutant D495R BACE1, which inhibits formation of this trimeric
complex, was shown to decrease the level of sAPPbeta. Overexpression of AP-2
promoted the internalization of BACE1 from the cell surface, thus reducing the
cell surface BACE1 level. As such, we concluded that HFD may induce the formation
of the BACE1/AP-2/clathrin complex, which is followed by its transport of BACE1
from the cell surface to the intracellular compartments. These events might be
associated with the enhancement of beta-site cleavage of APP in APP transgenic
mice. Here we present evidence that HFD, by regulation of subcellular trafficking
of BACE1, promotes APP cleavage.
PMID- 26414663
TI - HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral
Naive Patients in Turkey.
AB - HIV-1 replication is rapid and highly error-prone. Transmission of a drug
resistant HIV-1 strain is possible and occurs within the HIV-1-infected
population. In this study, we aimed to determine the prevalence of transmitted
drug resistance mutations (TDRMs) in 1,306 newly diagnosed untreated HIV-1
infected patients from 21 cities across six regions of Turkey between 2010 and
2015. TDRMs were identified according to the criteria provided by the World
Health Organization's 2009 list of surveillance drug resistance mutations. The
HIV-1 TDRM prevalence was 10.1% (133/1,306) in Turkey. Primary drug resistance
mutations (K65R, M184V) and thymidine analogue-associated mutations (TAMs) were
evaluated together as nucleos(t)ide reverse transcriptase inhibitor (NRTI)
mutations. NRTI TDRMs were found in 8.1% (107/1,306) of patients. However, TAMs
were divided into three categories and M41L, L210W, and T215Y mutations were
found for TAM1 in 97 (7.4%) patients, D67N, K70R, K219E/Q/N/R, T215F, and
T215C/D/S mutations were detected for TAM2 in 52 (3.9%) patients, and M41L +
K219N and M41L + T215C/D/S mutations were detected for the TAM1 + TAM2 profile in
22 (1.7%) patients, respectively. Nonnucleoside reverse transcriptase inhibitor
associated TDRMs were detected in 3.3% (44/1,306) of patients (L100I, K101E/P,
K103N/S, V179F, Y188H/L/M, Y181I/C, and G190A/E/S) and TDRMs to protease
inhibitors were detected in 2.3% (30/1,306) of patients (M46L, I50V, I54V, Q58E,
L76V, V82A/C/L/T, N83D, I84V, and L90M). In conclusion, long-term and large-scale
monitoring of regional levels of HIV-1 TDRMs informs treatment guidelines and
provides feedback on the success of HIV-1 prevention and treatment efforts.
PMID- 26414664
TI - Studying a Drug-like, RNA-Focused Small Molecule Library Identifies Compounds
That Inhibit RNA Toxicity in Myotonic Dystrophy.
AB - There are many RNA targets in the transcriptome to which small molecule chemical
probes and lead therapeutics are desired. However, identifying compounds that
bind and modulate RNA function in cellulo is difficult. Although rational design
approaches have been developed, they are still in their infancies and leave many
RNAs "undruggable". In an effort to develop a small molecule library that is
biased for binding RNA, we computationally identified "drug-like" compounds from
screening collections that have favorable properties for binding RNA and for
suitability as lead drugs. As proof-of-concept, this collection was screened for
binding to and modulating the cellular dysfunction of the expanded repeating RNA
(r(CUG)(exp)) that causes myotonic dystrophy type 1. Hit compounds bind the
target in cellulo, as determined by the target identification approach
Competitive Chemical Cross-Linking and Isolation by Pull-down (C-ChemCLIP), and
selectively improve several disease-associated defects. The best compounds
identified from our 320-member library are more potent in cellulo than compounds
identified by high-throughput screening (HTS) campaigns against this RNA.
Furthermore, the compound collection has a higher hit rate (9% compared to 0.01
3%), and the bioactive compounds identified are not charged; thus, RNA can be
"drugged" with compounds that have favorable pharmacological properties. Finally,
this RNA-focused small molecule library may serve as a useful starting point to
identify lead "drug-like" chemical probes that affect the biological
(dys)function of other RNA targets by direct target engagement.
PMID- 26414665
TI - Obituary: Fredric Brandt.
PMID- 26414666
TI - Surgical Deroofing Procedure for the Treatment of an Auricular Pseudocyst.
PMID- 26414667
TI - Tet oncogene family member 2 gene alterations in childhood acute myeloid
leukemia.
AB - BACKGROUND/PURPOSE: Mutations in the tet oncogene family member 2 gene (TET2) are
frequently found in adult patients with acute myeloid leukemia (AML). Reports of
TET2 mutations in children are limited. We assessed the prevalence of TET2
mutations in Taiwanese children with AML and analyzed their prognosis. METHODS:
Between 1997 and 2010, a total of 69 consecutive children with AML were enrolled
at the National Taiwan University Hospital. The analysis for TET2 mutations was
performed using direct sequencing. Clinical characteristics and overall survival
(OS) were compared between patients with and without TET2 alterations. RESULTS:
Intronic and missense mutations were identified. No nonsense or frameshift
mutations were observed. Two putative disease-causing missense mutations (S609C
and A1865G) were identified in one patient. We estimated the prevalence of TET2
mutations in the current patient population to be 1.4%. The most common
polymorphism was I1762V (45%), followed by V218M (12%), P29R (6%), and F868L
(6%). Patients with polymorphism I1762V had an increased 10-year survival rate
compared with patients without I1762V (48.4% vs. 25.7%, p = 0.049) by Chi-square
test; OS was not different when examined using the Kaplan-Meier method (p =
0.104). CONCLUSION: The prevalence of TET2 mutations in children with AML
compared with adults with AML was lower and less complex. Patient prognosis
associated with TET2 mutations in children requires further investigation.
PMID- 26414668
TI - The genomic bases of morphological divergence and reproductive isolation driven
by ecological speciation in Senecio (Asteraceae).
AB - Ecological speciation, driven by adaptation to contrasting environments, provides
an attractive opportunity to study the formation of distinct species, and the
role of selection and genomic divergence in this process. Here, we focus on a
particularly clear-cut case of ecological speciation to reveal the genomic bases
of reproductive isolation and morphological differences between closely related
Senecio species, whose recent divergence within the last ~200,000 years was
likely driven by the uplift of Mt. Etna (Sicily). These species form a hybrid
zone, yet remain morphologically and ecologically distinct, despite active gene
exchange. Here, we report a high-density genetic map of the Senecio genome and
map hybrid breakdown to one large and several small quantitative trait loci
(QTL). Loci under diversifying selection cluster in three 5 cM regions which are
characterized by a significant increase in relative (F(ST)), but not absolute
(d(XY)), interspecific differentiation. They also correspond to some of the
regions of greatest marker density, possibly corresponding to 'cold-spots' of
recombination, such as centromeres or chromosomal inversions. Morphological QTL
for leaf and floral traits overlap these clusters. We also detected three genomic
regions with significant transmission ratio distortion (TRD), possibly indicating
accumulation of intrinsic genetic incompatibilities between these recently
diverged species. One of the TRD regions overlapped with a cluster of high
species differentiation, and another overlaps the large QTL for hybrid breakdown,
indicating that divergence of these species may have occurred due to a complex
interplay of ecological divergence and accumulation of intrinsic genetic
incompatibilities.
PMID- 26414669
TI - Brain contrasting ability of blood-brain-barrier-permeable nitroxyl contrast
agents for magnetic resonance redox imaging.
AB - PURPOSE: The detailed in vivo T1 -weighted contrasting abilities of nitroxyl
contrast agents, which have been used as redox responsive contrast agents in
several magnetic resonance-based imaging modalities, in mouse brain were
investigated. METHODS: Distribution and pharmacokinetics of five types of five
membered-ring nitroxyl radical compound were compared using T1 -weighted MRI.
RESULTS: The blood-brain barrier (BBB) -impermeable 3-carboxy-2,2,5,5
tetramethylpyrrolidine-N-oxyl (CxP) could not be distributed in the brain. The
slightly lipophilic 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP)
showed slight distribution only in the ventricle, but not in the medulla and
cortex. The amphiphilic 3-methoxy-carbonyl-2,2,5,5-tetramethyl-pyrrolidine-N-oxyl
(MCP) had good initial uniform distribution in the brain and showed typical 2
phase signal decay profiles. A brain-seeking nitroxyl probe, acetoxymethyl
2,2,5,5-tetramethyl-pyrrolidine-N-oxyl-3-carboxylate (CxP-AM), showed an
accumulating phase, and then its accumulation was maintained in the medulla and
ventricle regions, but not in the cortex. The lipophilic 4-(N-methyl piperidine)
2,2,5,5-tetramethylpyrroline-N-oxyl (23c) was well distributed in the cortex and
medulla, but slightly in the ventricle, and showed relatively rapid linear signal
decay. CONCLUSION: Nitroxyl contrast agents equipped with a suitable lipophilic
substitution group could be BBB-permeable functional contrast agents. MR redox
imaging, which can estimate not only the redox characteristics but also the
detailed distribution of the contrast agents, is a good candidate for a
theranostic tool. Magn Reson Med 76:935-945, 2016. (c) 2015 Wiley Periodicals,
Inc.
PMID- 26414671
TI - Correction to "Copper(I)-Catalyzed Borylative exo-Cyclization of Alkenyl Halides
Containing Unactivated Double Bond".
PMID- 26414672
TI - A game of snakes and ladders: negotiating the 'ups and downs' of endorsement as a
nurse practitioner in Australia.
AB - BACKGROUND: Australian legislation supporting the nurse practitioner (NP) role
was enacted in 1998. Since then, NPs have played an important advanced practice
role within the interdisciplinary healthcare team. However, the literature
suggests that transition to the NP role can be challenging. AIM: This paper
highlights the complex transition experiences of ten recently endorsed Australian
NPs. The convoluted legislative and regulatory requirements that were negotiated
by the NPs are presented as narratives. METHODS: Informed by an ethnographic
approach, participants were interviewed several times during their first year.
Interview transcripts were thematically analysed and aggregated into three
narratives representative of key findings. KEY FINDINGS: The findings exemplify
the complexity of navigating through a labyrinth of bureaucracy and the extensive
negotiations required to appease those who yielded power over their future
practice. CONCLUSION: This study raises awareness of the transition experiences
of Australian NPs and their challenges and barriers during this time.
PMID- 26414670
TI - Shared Decision Making for Antidepressants in Primary Care: A Cluster Randomized
Trial.
AB - IMPORTANCE: For antidepressants, the translation of evidence of comparative
effectiveness into practice is suboptimal. This deficit directly affects outcomes
and quality of care for patients with depression. To overcome this problem, we
developed the Depression Medication Choice (DMC) encounter decision aid, designed
to help patients and clinicians consider the available antidepressants and the
extent to which they improved depression and other issues important to patients.
OBJECTIVE: Estimate the effect of DMC on quality of the decision-making process
and depression outcomes. DESIGN, SETTING, AND PARTICIPANTS: We conducted a
cluster randomized trial of adults with moderate to severe depression considering
treatment with an antidepressant. Primary care practices in 10 rural, suburban,
and urban primary care practices across Minnesota and Wisconsin were randomly
allocated to treatment of depression with or without use of the DMC decision aid.
INTERVENTION: Depression Medication Choice, a series of cards, each highlighting
the effect of the available options on an issue of importance to patients for use
during face-to-face consultations. MAIN OUTCOMES AND MEASURES: Decision-making
quality as judged by patient knowledge and involvement in decision making,
patient and clinician decisional comfort (Decisional Conflict Scale) and
satisfaction, encounter duration, medication adherence, depression symptoms, and
the Patient Health Questionnaire for depression (PHQ-9). RESULTS: We enrolled 117
clinicians and 301 patients (67% women; mean [SD] age, 44 [15] years; mean [SD]
PHQ-9 score, 15 [4]) into the trial. Compared with usual care (UC), use of DMC
significantly improved patients' decisional comfort (DMC, 80% vs UC, 75%; P =
.02), knowledge (DMC, 65% vs UC, 56%; P = .03), satisfaction (risk ratio [RR],
from 1.25 [P = .81] to RR, 2.4 [P = .002] depending on satisfaction domain), and
involvement (DMC, 47% vs UC, 33%; P<.001). It also improved clinicians'
decisional comfort (DMC, 80% vs UC, 68%; P < .001) and satisfaction (RR, 1.64; P
= .02). There were no differences in encounter duration, medication adherence, or
improvement of depression control between arms. CONCLUSIONS AND RELEVANCE: The
DMC decision aid helped primary care clinicians and patients with moderate to
severe depression select antidepressants together, improving the decision-making
process without extending the visit. On the other hand, DMC had no discernible
effect on medication adherence or depression outcomes. By translating comparative
effectiveness into patient-centered care, use of DMC improved the quality of
primary care for patients with depression. TRIAL REGISTRATION: clinicaltrials.gov
Identifier: NCT01502891.
PMID- 26414673
TI - Efficacy of an Interinstitutional Mentoring Program Within Pediatric
Rheumatology.
AB - OBJECTIVE: The small size of many pediatric rheumatology programs translates into
limited mentoring options for early career physicians. To address this problem,
the American College of Rheumatology (ACR) and the Childhood Arthritis and
Rheumatology Research Alliance (CARRA) developed a subspecialty-wide
interinstitutional mentoring program, the ACR/CARRA Mentoring Interest Group
(AMIGO). We sought to assess the impact of this program on mentoring within
pediatric rheumatology. METHODS: In a longitudinal 3-year study, participant
ratings from the AMIGO pilot program were compared with those after the program
was opened to general enrollment. Access to mentoring as a function of career
stage was assessed by surveys of the US and Canadian pediatric rheumatologists in
2011 and 2014, before and after implementation of AMIGO. RESULTS: Participants in
the pilot phase (19 dyads) and the general implementation phase (112 dyads)
reported comparable success in establishing mentor contact, suitability of mentor
mentee pairing, and benefit with respect to career development, scholarship, and
work-life balance. Community surveys showed that AMIGO participation as mentee
was high among fellows (86%) and modest among junior faculty (31%).
Implementation correlated with significant gains in breadth of mentorship and in
overall satisfaction with mentoring for fellows but not junior faculty.
CONCLUSION: AMIGO is a career mentoring program that serves most fellows and many
junior faculty in pediatric rheumatology across the US and Canada. Program
evaluation data confirm that a subspecialty-wide interinstitutional mentoring
program is feasible and can translate into concrete improvement in mentoring,
measurable at the level of the whole professional community.
PMID- 26414675
TI - Mouse models of intestinal cancer.
AB - Murine models of intestinal cancer are powerful tools to recapitulate human
intestinal cancer, understand its biology and test therapies. With recent
developments identifying the importance of the tumour microenvironment and the
potential for immunotherapy, autochthonous genetically engineered mouse models
(GEMMs) will remain an important part of preclinical studies for the foreseeable
future. This review will provide an overview of the current mouse models of
intestinal cancer, from the Apc(Min/+) mouse, which has been used for over 25
years, to the latest 'state-of-the-art' organoid models. We discuss here how
these models have been used to define fundamental processes involved in tumour
initiation and the attempts to generate metastatic models, which is the ultimate
cause of cancer mortality. Together these models will provide key insights to
understand this complex disease and hopefully will lead to the discovery of new
therapeutic strategies.
PMID- 26414676
TI - An atlas of genetic correlations across human diseases and traits.
AB - Identifying genetic correlations between complex traits and diseases can provide
useful etiological insights and help prioritize likely causal relationships. The
major challenges preventing estimation of genetic correlation from genome-wide
association study (GWAS) data with current methods are the lack of availability
of individual-level genotype data and widespread sample overlap among meta
analyses. We circumvent these difficulties by introducing a technique-cross-trait
LD Score regression-for estimating genetic correlation that requires only GWAS
summary statistics and is not biased by sample overlap. We use this method to
estimate 276 genetic correlations among 24 traits. The results include genetic
correlations between anorexia nervosa and schizophrenia, anorexia and obesity,
and educational attainment and several diseases. These results highlight the
power of genome-wide analyses, as there currently are no significantly associated
SNPs for anorexia nervosa and only three for educational attainment.
PMID- 26414679
TI - Transepithelial Transport of PAMAM Dendrimers Across Isolated Human Intestinal
Tissue.
AB - Poly(amido amine) (PAMAM) dendrimers have shown transepithelial transport across
intestinal epithelial barrier in rats and across Caco-2 cell monolayers. Caco-2
models innately lack mucous barriers, and rat isolated intestinal tissue has been
shown to overestimate human permeability. This study is the first report of
transport of PAMAM dendrimers across isolated human intestinal epithelium. It was
observed that FITC labeled G4-NH2 and G3.5-COOH PAMAM dendrimers at 1 mM
concentration do not have a statistically higher permeability compared to free
FITC controls in isolated human jejunum and colonic tissues. Mannitol
permeability was increased at 10 mM concentrations of G3.5-COOH and G4-NH2
dendrimers. Significant histological changes in human colonic and jejunal tissues
were observed at G3.5-COOH and G4-NH2 concentrations of 10 mM implying that dose
limiting toxicity may occur at similar concentrations in vivo. The permeability
through human isolated intestinal tissue in this study was compared to previous
rat and Caco-2 permeability data. This study implicates that PAMAM dendrimer oral
drug delivery may be feasible, but it may be limited to highly potent drugs.
PMID- 26414678
TI - Partitioning heritability by functional annotation using genome-wide association
summary statistics.
AB - Recent work has demonstrated that some functional categories of the genome
contribute disproportionately to the heritability of complex diseases. Here we
analyze a broad set of functional elements, including cell type-specific
elements, to estimate their polygenic contributions to heritability in genome
wide association studies (GWAS) of 17 complex diseases and traits with an average
sample size of 73,599. To enable this analysis, we introduce a new method,
stratified LD score regression, for partitioning heritability from GWAS summary
statistics while accounting for linked markers. This new method is
computationally tractable at very large sample sizes and leverages genome-wide
information. Our findings include a large enrichment of heritability in conserved
regions across many traits, a very large immunological disease-specific
enrichment of heritability in FANTOM5 enhancers and many cell type-specific
enrichments, including significant enrichment of central nervous system cell
types in the heritability of body mass index, age at menarche, educational
attainment and smoking behavior.
PMID- 26414680
TI - Exposure to flour dust in the occupational environment.
AB - Exposure to flour dust can be found in the food industry and animal feed
production. It may result in various adverse health outcomes from conjunctivitis
to baker's asthma. In this paper, flour dust exposure in the above-mentioned
occupational environments is characterized and its health effects are discussed.
A peer-reviewed literature search was carried out and all available published
materials were included if they provided information on the above-mentioned
elements. The hitherto conducted studies show that different components of flour
dust like enzymes, proteins and baker's additives can cause both non-allergic and
allergic reactions among exposed workers. Moreover, the problem of exposure to
cereal allergens present in flour dust can also be a concern for bakers' family
members. Appreciating the importance of all these issues, the exposure assessment
methods, hygienic standards and preventive measures are also addressed in this
paper.
PMID- 26414681
TI - Can Creatine Supplementation Improve Body Composition and Objective Physical
Function in Rheumatoid Arthritis Patients? A Randomized Controlled Trial.
AB - OBJECTIVE: Rheumatoid cachexia (muscle wasting) in rheumatoid arthritis (RA)
patients contributes to substantial reductions in strength and impaired physical
function. The objective of this randomized controlled trial was to investigate
the effectiveness of oral creatine (Cr) supplementation in increasing lean mass
and improving strength and physical function in RA patients. METHODS: In a double
blind design, 40 RA patients were randomized to either 12 weeks' supplementation
of Cr or placebo. Body composition (dual x-ray absorptiometry and bioelectrical
impedance spectroscopy [BIS]), strength, and objectively assessed physical
function were measured at baseline, day 6, week 12, and week 24. Data analysis
was performed by analysis of covariance. RESULTS: Cr supplementation increased
appendicular lean mass (ALM; a surrogate measure of muscle mass) by mean +/- SE
0.52 +/- 0.13 kg (P = 0.004 versus placebo), and total LM by 0.60 +/- 0.37 kg (P
= 0.158). The change in LM concurred with the gain in intracellular water (0.64
+/- 0.22 liters; P = 0.035) measured by BIS. Despite increasing ALM, Cr
supplementation, relative to placebo, failed to improve isometric knee extensor
strength (P = 0.408), handgrip strength (P = 0.833), or objectively assessed
physical function (P = 0.335-0.764). CONCLUSION: In patients with RA, Cr
supplementation increased muscle mass, but not strength or objective physical
function. No treatment-related adverse effects were reported, suggesting that Cr
supplementation may offer a safe and acceptable adjunct treatment for attenuating
muscle loss; this treatment may be beneficial for patients experiencing severe
rheumatoid cachexia.
PMID- 26414682
TI - Tooth Tissue Engineering: The Importance of Blood Products as a Supplement in
Tissue Culture Medium for Human Pulp Dental Stem Cells.
AB - One of the goals in using cells for tissue engineering (TE) and cell therapy
consists of optimizing the medium for cell culture. The present study compares
three different blood product supplements for improved cell proliferation and
protection against DNA damage in cultured human dental pulp stem cells for tooth
TE applications. Human cells from dental pulp were first characterized as adult
stem cells (ectomesenchymal mixed origin) by flow cytometry. Next, four different
cell culture conditions were tested: I, supplement-free; II, supplemented with
fetal bovine serum; III, allogeneic human serum; and IV, autologous human serum.
Cultured cells were then characterized for cell proliferation, mineralized nodule
formation, and colony-forming units (CFU) capability. After 28 days in culture,
the comet assay was performed to assess possible damage in cellular DNA. Our
results revealed that Protocol IV achieved higher cell proliferation than
Protocol I (p = 0.0112). Protocols II and III resulted in higher cell
proliferation than Protocol I, but no statistical differences were found relative
to Protocol IV. The comet assay revealed less cell damage in cells cultured using
Protocol IV as compared to Protocols II and III. The damage percentage observed
on Protocol II was significantly higher than all other protocols. CFUs capability
was highest using Protocol IV (p = 0.0018) and III, respectively, and the highest
degree of mineralization was observed using Protocol IV as compared to Protocols
II and III. Protocol IV resulted in significantly improved cell proliferation,
and no cell damage was observed. These results demonstrate that human blood
product supplements can be used as feasible supplements for culturing adult human
dental stem cells.
PMID- 26414685
TI - Origin of Noise in Layered MoTe2 Transistors and its Possible Use for
Environmental Sensors.
AB - Low-frequency current fluctuations are monitored and the mechanism of electric
noise investigated in layered 2H-type alpha-molybdenum ditelluride transistors.
The charge transport mechanism of electric noise in atomically thin transition
metal dichalcogenides is studied under different environments; the development of
a new sensing functionality may be stimulated.
PMID- 26414683
TI - The effect of oppositional parietal transcranial direct current stimulation on
lateralized brain functions.
AB - Cognitive functions such as numerical processing and spatial attention show
varying degrees of lateralization. Transcranial direct current stimulation (tDCS)
can be used to investigate how modulating cortical excitability affects
performance of these tasks. This study investigated the effect of bi-parietal
tDCS on numerical processing, spatial and sustained attention. It was
hypothesized that tDCS would have distinct effects on these tasks because of
varying lateralization (numerical processing left, spatial attention right) and
that these effects are partly mediated by modulation of sustained attention. A
single-blinded, crossover, sham-controlled study was performed. Eighteen healthy
right-handed participants performed cognitive tasks during three sessions of
oppositional parietal tDCS stimulation: sham; right anodal with left cathodal
(RA/LC); and right cathodal with left anodal (RC/LA). Participants performed a
number comparison task, a modified Posner task, a choice reaction task (CRT) and
the rapid visual processing task (RVP). RA/LC tDCS impaired number comparison
performance compared with sham, with slower responses to numerically close
numbers pairs. RA/LC and RC/LA tDCS had distinct effects on CRT performance,
specifically affecting vigilance level during the final block of the task. No
effect of stimulation on the Posner task or RVP was found. It was demonstrated
that oppositional parietal tDCS affected both numerical performance and vigilance
level in a polarity-dependent manner. The effect of tDCS on numerical processing
may partly be due to attentional effects. The behavioural effects of tDCS were
specifically observed under high task demands, demonstrating the consequences of
an interaction between stimulation type and cognitive load.
PMID- 26414684
TI - How does HTLV-1 cause adult T-cell leukaemia/lymphoma (ATL)?
AB - A typical person infected with the retrovirus human T-lymphotropic virus type 1
(HTLV-1) carries tens of thousands of clones of HTLV-1-infected T lymphocytes,
each clone distinguished by a unique integration site of the provirus in the host
genome. However, only 5% of infected people develop the malignant disease adult T
cell leukaemia/lymphoma, usually more than 50 years after becoming infected. We
review the host and viral factors that cause this aggressive disease.
PMID- 26414687
TI - Revisiting the tale of venous thromboembolism in hospitalized medical patients.
PMID- 26414686
TI - Protracted effects of chronic stress on serotonin-dependent thermoregulation.
AB - Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain
and to alter body temperature. The body temperature is controlled in part, by the
medial preoptic area (mPOA) of the hypothalamus. To investigate the effect of
chronic stress on 5HT and how it affects body temperature regulation, we examined
whether exposure to a chronic unpredictable stress (CUS) paradigm produces long
term alterations in thermoregulatory function of the mPOA through decreased 5HT
neurotransmission. Adult male Sprague-Dawley rats underwent 21 d of CUS. Four
days after the last stress exposure, basal body temperature in the home cage and
body temperature in a cold room maintained at 10 degrees C were recorded. The
CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h
compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to
significantly elevate body temperature from basal levels at 30 and 60 min of
exposure to the cold room, the CUS rats showed a hypothermic response to the
cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor,
blocked stress-induced decrease in body temperature in response to the cold
challenge. CUS also decreased 5HT transporter protein immunoreactivity in the
mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused
stressed rats to exhibit a sensitized hyperthermic response to cold. These
results indicate that the CUS induced changes to the 5HTergic system alter mPOA
function in thermoregulation. These findings help us to explain the mechanisms
underlying chronic stress-induced disorders such as chronic fatigue syndrome
wherein long lasting thermoregulatory deficits are observed.
PMID- 26414688
TI - Future treatment options for human African trypanosomiasis.
AB - Over the past 17 years, the number of reported cases of human African
trypanosomiasis (HAT) has declined by over 90%, a significant result since the
disease was highlighted as a public health problem by the WHO in 1995. However,
if the goal of eliminating HAT by 2020 is to be achieved, then new treatments
need to be identified and developed. A plethora of compound collections has been
screened against Trypanosoma brucei spp, the etiological agents of HAT, resulting
in three compounds progressing to clinical development. However, due to the high
attrition rates in drug discovery, it is essential that research continues to
identify novel molecules. Failure to do so, will result in the absence of
molecules in the pipeline to fall back on should the current clinical trials be
unsuccessful. This could seriously compromise control efforts to date, resulting
in a resurgence in the number of HAT cases.
PMID- 26414689
TI - Do normal head ultrasounds need repeating in infants less than 30 weeks
gestation?
AB - OBJECTIVE: Current head ultrasound (HUS) screening recommendations in preterm
infants often include a repeat HUS, regardless of initial findings. The objective
of this study is to determine the rate of subsequent severe intraventricular
hemorrhage (IVH), ventriculomegaly (VM), or periventricular leukomalacia (PVL)
among infants < 30 weeks gestation (EGA) with a normal HUS at day of life (DOL) 4
10. METHODS: Retrospectively collected data were analyzed for all infants < 30
weeks EGA cared for in one NICU from 1 January 2010 to 31 August 2014. Infants
with severe congenital anomalies were excluded. We reviewed the first three HUSs
and last documented HUS. Severe IVH was defined as > Papile grade 2 and
significant interval HUS change was defined as development of severe IVH, PVL, or
VM. RESULTS: Of the 383 infants who had an initial screening HUS between DOL 4
and 10, 258 (67%) were initially normal and repeat screening was performed in 228
of these. None developed severe IVH on follow-up HUS. One infant developed VM
secondary to GBS meningitis, and one developed echogenicity concerning for PVL
that later resolved. CONCLUSIONS: Among very preterm infants with a normal HUS
between DOL 4 and 10, routine follow-up HUS is unlikely to identify a significant
change.
PMID- 26414677
TI - Large-scale genomic analyses link reproductive aging to hypothalamic signaling,
breast cancer susceptibility and BRCA1-mediated DNA repair.
AB - Menopause timing has a substantial impact on infertility and risk of disease,
including breast cancer, but the underlying mechanisms are poorly understood. We
report a dual strategy in ~70,000 women to identify common and low-frequency
protein-coding variation associated with age at natural menopause (ANM). We
identified 44 regions with common variants, including two regions harboring
additional rare missense alleles of large effect. We found enrichment of signals
in or near genes involved in delayed puberty, highlighting the first molecular
links between the onset and end of reproductive lifespan. Pathway analyses
identified major association with DNA damage response (DDR) genes, including the
first common coding variant in BRCA1 associated with any complex trait. Mendelian
randomization analyses supported a causal effect of later ANM on breast cancer
risk (~6% increase in risk per year; P = 3 * 10(-14)), likely mediated by
prolonged sex hormone exposure rather than DDR mechanisms.
PMID- 26414691
TI - Reactions of Th(+) + H2, D2, and HD Studied by Guided Ion Beam Tandem Mass
Spectrometry and Quantum Chemical Calculations.
AB - Kinetic energy dependent reactions of Th(+) with H2, D2, and HD were studied
using a guided ion beam tandem mass spectrometer. Formation of ThH(+) and ThD(+)
is endothermic in all cases with similar thresholds. Branching ratio results for
the reaction with HD indicate that Th(+) reacts via a statistical mechanism,
similar to Hf(+). The kinetic energy dependent cross sections for formation of
ThH(+) and ThD(+) were evaluated to determine a 0 K bond dissociation energy
(BDE) of D0(Th(+)-H) = 2.45 +/- 0.07 eV. This value is in good agreement with a
previous result obtained from analysis of the Th(+) + CH4 reaction. D0(Th(+)-H)
is observed to be larger than its transition metal congeners, TiH(+), ZrH(+), and
HfH(+), believed to be a result of lanthanide contraction. The reactions with H2
were also explored using quantum chemical calculations that include a
semiempirical estimation and explicit calculation of spin-orbit contributions.
These calculations agree nicely and indicate that ThH(+) most likely has a
(3)Delta1 ground level with a low-lying (1)Sigma(+) excited state. Theory also
provides the reaction potential energy surfaces and BDEs that are in reasonable
agreement with experiment.
PMID- 26414690
TI - Hypoalbuminemia at admission is associated with increased incidence of in
hospital complications in geriatric trauma patients.
AB - BACKGROUND: Elderly patients are at an increased risk of protein-energy
malnutrition (PEM) which increases the risk of morbidity/mortality. We evaluated
the association between hypoalbuminemia at the time of emergency department (ED)
admission and in-hospital complications among geriatric trauma patients. METHODS:
This was an ambidirectional cohort study of geriatric (>=55 years) trauma
patients treated at a Level I trauma center between May 2013 and March 2014. The
exposure of interest was albumin level at ED admission (<3.6 g/dL [PEM] or >=3.6
g/dL (No PEM)]. The outcome of interest was 30-day incidence of complications.
RESULTS: A total of 130 patients met study eligibility. Of these, 85 (65%)
patients were in the PEM group. After adjusting for tube feeding and injury
severity score, PEM at admission was associated with a 2-fold increase in the
risk of 30-day overall hospital complications (hazard ratio 2.1, 95% confidence
interval 1.1 to 3.8). CONCLUSION: Serum albumin level at ED admission, but not
prealbumin level, is a significant predictor of in-hospital complications in
geriatric trauma patients.
PMID- 26414692
TI - Discontinued dermatological drugs in 2014.
AB - INTRODUCTION: Dermatology is a relatively small field concerned with conditions
of the hair, skin, nails and their related diseases; yet there is considerable
active research and development within the field. Pharmaceutical companies seek
more effective treatments through various therapeutic classes and delivery
routes. However, 28 drugs have been discontinued for the treatment of
dermatologic diseases in 2014. AREAS COVERED: Herein, the authors summarize the
details about each discontinued drug in 2014. The dermatological conditions
covered are: psoriasis, eczema, leg ulcers, wounds, allergies, acne, scleroderma,
lupus erythematosus, urticaria, mastocytosis, epidermolysis bullosa,
onychomycosis and one other unspecified disease. The authors also provide
suggestions for improving and accelerating the future of dermatological drug
development. EXPERT OPINION: It is clear that improved metrics, especially for
early assessment, emphasizing clinical relevance, are necessary to increase
success rate. Transparency and clear communication within the field is necessary
to reduce and salvage the waste that accumulates from these costly studies.
Focused attention on how preclinical and early clinical studies failed to
indicate subsequent toxicity profiles in patients would accelerate drug
development. Distinguishing between disappointing study results and
business/financial factors is important when analyzing discontinuations. A
reformed approach toward study design would aid both. Ultimately, relevance and
practicality for the patient must be kept in mind at all times.
PMID- 26414694
TI - Deep venous thrombosis in the nonoperated leg after primary major lower extremity
arthroplasty: a retrospective study based on diagnosis using venography.
AB - Venous thromboembolism (VTE) is a common complication after major orthopedic
surgery. However, the reported rates of deep venous thrombosis (DVT) vary widely.
Our aim was to study the incidence of DVT in the nonoperated leg after primary
major lower extremity arthroplasty using bilateral venography. The records of
patients who underwent total hip arthroplasty (THA) or total knee arthroplasty
(TKA) at our institution between August 2013 and August 2014 were reviewed. We
examined the records for a total of 380 patients, of which 244 had undergone
bilateral venography 3-5 days after THA or TKA. A total of 244 patients
undergoing TKA (n = 119) or THA (n = 125) were recruited for this study. DVT was
diagnosed in 42 (17.2%) of the 244 patients; nine patients developed DVT in both
legs, and four developed DVT only in the nonoperated leg. All of the DVTs were
located in calf veins. DVT occurred more frequently after TKA than THA,
especially in muscular veins. Female sex and older age were found to be positive
risk factors for DVT after THA. The incidence of DVT after major lower
arthroplasty is high. DVT in nonoperated legs should be carefully considered
because of its potential risks, especially in left. Distal DVT also has a high
risk to develop pulmonary embolism (PE). The combination of anticoagulant and
pneumatic compression is a good measure to avoid proximal DVT, and it is well
tolerated to stop anticoagulant if the patients were diagnosed as having no DVT.
PMID- 26414693
TI - Three-Dimensional Neural Spheroid Culture: An In Vitro Model for Cortical
Studies.
AB - There is a high demand for in vitro models of the central nervous system (CNS) to
study neurological disorders, injuries, toxicity, and drug efficacy. Three
dimensional (3D) in vitro models can bridge the gap between traditional two
dimensional culture and animal models because they present an in vivo-like
microenvironment in a tailorable experimental platform. Within the expanding
variety of sophisticated 3D cultures, scaffold-free, self-assembled spheroid
culture avoids the introduction of foreign materials and preserves the native
cell populations and extracellular matrix types. In this study, we generated 3D
spheroids with primary postnatal rat cortical cells using an accessible, size
controlled, reproducible, and cost-effective method. Neurons and glia formed
laminin-containing 3D networks within the spheroids. The neurons were
electrically active and formed circuitry through both excitatory and inhibitory
synapses. The mechanical properties of the spheroids were in the range of brain
tissue. These in vivo-like features of 3D cortical spheroids provide the
potential for relevant and translatable investigations of the CNS in vitro.
PMID- 26414695
TI - Prescribing patterns of target-specific oral anticoagulants: an academic hospital
perspective.
AB - Target-specific oral anticoagulants have been rapidly adopted into clinical
practice for stroke prophylaxis and venous thromboembolism treatment, raising
concerns about off-label prescribing practices. We conducted a retrospective
review of consecutive patients prescribed dabigatran, rivaroxaban or apixaban
prior to inpatient hospitalization over an 18-month period to examine the off
label prescribing frequency, contraindications and related complications. Chart
review included baseline demographics, hospital admitting service, outpatient
prescribing service, renal function, therapeutic indication, echocardiographic
findings, contraindications, major bleeding events and vital status. We
identified 160 patients who received a target-specific oral anticoagulant prior
to hospitalization. Over half (53.1%) of the patients received rivaroxaban, 43.7%
received dabigatran and 3.1% received apixaban. Atrial fibrillation (68.1%) and
venous thromboembolism treatment (25.6%) were the most common indications. Ninety
percent of patients had a U.S. Foods and Drugs Administration (FDA)-approved
indication for therapy. Major bleeding events occurred in 4.4% of patients.
Cardiology was the most common prescribing and admitting service (43.8 and
31.3%), and more frequently adhered to FDA-approved indications (97 vs. 84%, P =
0.01). There were no significant differences between prescribing services
regarding major contraindications (P = 0.14) and major bleeding events (P =
0.77). Off-label prescription rates for target-specific oral anticoagulants were
infrequent and not associated with increased adverse events.
PMID- 26414696
TI - Exercise Therapy for Parkinson's Disease: Pedaling Rate Is Related to Changes in
Motor Connectivity.
AB - Forced-rate lower-extremity exercise has recently emerged as a potential safe and
low-cost therapy for Parkinson's disease (PD). The efficacy is believed to be
dependent on pedaling rate, with rates above the subjects' voluntary exercise
rates being most beneficial. In this study, we use functional connectivity
magnetic resonance imaging (MRI) to further elucidate the mechanism underlying
this effect. Twenty-seven PD patients were randomized to complete 8 weeks of
forced-rate exercise (FE) or voluntary-rate exercise (VE). Exercise was delivered
using a specialized stationary bicycle, which can augment patients' voluntary
exercise rates. The FE group received assistance from the cycle. Imaging was
conducted at baseline, end of therapy, and after 4 weeks of follow-up. Functional
connectivity (FC) was determined via seed-based correlation analysis, using
activation-based seeds in the primary motor cortex (M1). The change in FC after
exercise was compared using linear correlation with pedaling rate. Results of the
correlation analysis showed a strong positive correlation between pedaling rate
and change in FC from the most affected M1 to the ipsilateral thalamus. This
effect persisted after 4 weeks of follow-up. These results indicate that a
plausible mechanism for the therapeutic efficacy of high-rate exercise in PD is
that it improves thalamo-cortical connectivity.
PMID- 26414698
TI - From the Editors.
PMID- 26414699
TI - Nonparametric Estimation of the Probability of Detection of Flaws in an
Industrial Component, from Destructive and Nondestructive Testing Data, Using
Approximate Bayesian Computation.
AB - We consider the problem of estimating the probability of detection (POD) of flaws
in an industrial steel component. Modeled as an increasing function of the flaw
height, the POD characterizes the detection process; it is also involved in the
estimation of the flaw size distribution, a key input parameter of physical
models describing the behavior of the steel component when submitted to extreme
thermodynamic loads. Such models are used to assess the resistance of highly
reliable systems whose failures are seldom observed in practice. We develop a
Bayesian method to estimate the flaw size distribution and the POD function,
using flaw height measures from periodic in-service inspections conducted with an
ultrasonic detection device, together with measures from destructive lab
experiments. Our approach, based on approximate Bayesian computation (ABC)
techniques, is applied to a real data set and compared to maximum likelihood
estimation (MLE) and a more classical approach based on Markov Chain Monte Carlo
(MCMC) techniques. In particular, we show that the parametric model describing
the POD as the cumulative distribution function (cdf) of a log-normal
distribution, though often used in this context, can be invalidated by the data
at hand. We propose an alternative nonparametric model, which assumes no
predefined shape, and extend the ABC framework to this setting. Experimental
results demonstrate the ability of this method to provide a flexible estimation
of the POD function and describe its uncertainty accurately.
PMID- 26414697
TI - Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus
and esophageal adenocarcinoma.
AB - The strong male predominance in Barrett's esophagus (BE) and esophageal
adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be
involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the
androgen pathway influence risk of developing BE and EAC. This genetic
epidemiological analysis included 14 studies from Australia, Europe and North
America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed
using a gene-based approach: versatile gene-based test association study. This
method evaluates associations between a trait and all SNPs within a specific gene
rather than each SNP marker individually as in a conventional GWAS. The data were
stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and
gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383
BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were
associated with risk of BE in the sexes combined (p = 0.002) and in males (p =
0.003), but not in females separately (p = 0.3). This association was found in
tobacco smokers (p = 0.003) and in BE patients without reflux (p = 0.004), but
not in nonsmokers (p = 0.2) or those with reflux (p = 0.036). SNPs within JMJD1C
were associated with risk of EAC in females (p = 0.001). However, none of these
associations replicated in a subsequent sample. Fourteen other genes studied did
not reach statistically significant levels of association with BE, EAC or the
combination of BE and EAC, after correcting for the number of genes included in
the analysis. In conclusion, genetic variants in the androgen-related genes
CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but
replication data with larger sample sizes are needed.
PMID- 26414703
TI - The Course and Predictors of Health-Related Quality of Life in Living Kidney
Donors: A Systematic Review and Meta-Analysis.
AB - A better understanding of the course and risk factors for impaired long-term
health-related quality of life (HRQoL; ie, physical, psychological, and social
relational functioning) after kidney donation might help clinicians improve the
care of live kidney donors. This systematic review and meta-analysis summarizes
prospective studies about the course and predictors of HRQoL in living kidney
donors. Studies indicate that shortly after donation, donors have lower HRQoL,
with minor to moderate changes in psychological and social-relational functioning
and major changes in physical functioning. At 3-12 months after donation, HRQoL
returned to baseline or was slightly reduced, particularly for fatigue, but
scores were still comparable to general population norms. Results were mainly
robust across surgery techniques. A limited number of studies examined risk
factors for impaired HRQoL, with low psychological functioning before donation as
the most consistent predictor. Based on these results, clinicians can inform
potential donors that, on average, kidney donors have high long-term HRQoL;
however, donors with low psychological functioning at baseline are those most at
risk of impaired long-term HRQoL. Future studies should focus on other
potentially relevant predictors of postdonation HRQoL, including donor
eligibility criteria and donor-recipient relationships, to optimize screening and
interventions for donors at risk.
PMID- 26414700
TI - Robotic Rehabilitator of the Rodent Upper Extremity: A System and Method for
Assessing and Training Forelimb Force Production after Neurological Injury.
AB - Rodent models of spinal cord injury are critical for the development of
treatments for upper limb motor impairment in humans, but there are few methods
for measuring forelimb strength of rodents, an important outcome measure. We
developed a novel robotic device--the Robotic Rehabilitator of the Rodent Upper
Extremity (RUE)--that requires rats to voluntarily reach for and pull a bar to
retrieve a food reward; the resistance of the bar can be programmed. We used RUE
to train forelimb strength of 16 rats three times per week for 23 weeks before
and 38 weeks after a mild (100 kdyne) unilateral contusion at the cervical level
5 (C5). We measured maximum force produced when RUE movement was unexpectedly
blocked. We compared this blocked pulling force (BPF) to weekly measures of
forelimb strength obtained with a previous, well-established method: the grip
strength meter (GSM). Before injury, BPF was 2.6 times higher (BPF, 444.6 +/-
19.1 g; GSM, 168.4 +/- 3.1 g) and 4.9 times more variable (p < 0.001) than
pulling force measured with the GSM; the two measurement methods were
uncorrelated (R(2) = 0.03; p = 0.84). After injury, there was a significant
decrease in BPF of 134.35 g +/- 14.71 g (p < 0.001). Together, our findings
document BPF as a repeatable measure of forelimb force production, sensitive to a
mild spinal cord injury, which comes closer to measuring maximum force than the
GSM and thus may provide a useful measure for quantifying the effects of
treatment in rodent models of SCI.
PMID- 26414704
TI - Lichen-associated fungi from Paleogene amber.
PMID- 26414702
TI - Altered Hypoxic-Adenosine Axis and Metabolism in Group III Pulmonary
Hypertension.
AB - Group III pulmonary hypertension (PH) is a highly prevalent and deadly lung
disorder with limited treatment options other than transplantation. Group III PH
affects patients with ongoing chronic lung injury, such as idiopathic pulmonary
fibrosis (IPF). Between 30 and 40% of patients with IPF are diagnosed with PH.
The diagnosis of PH has devastating consequences to these patients, leading to
increased morbidity and mortality, yet the molecular mechanisms involved in the
development of PH in patients with chronic lung disease remain elusive. Our
hypothesis was that the hypoxic-adenosinergic system is enhanced in patients with
group III PH compared with patients with IPF with no PH. Explanted lung tissue
was analyzed for markers of the hypoxic-adenosine axis, including expression
levels of hypoxia-inducible factor (HIF)-1A, adenosine A2B receptor, CD73, and
equilibrative nucleotide transporter-1. In addition, we assessed whether altered
mitochondrial metabolism was present in these samples. Increased expression of
HIF-1A was observed in tissues from patients with group III PH. These changes
were consistent with increased evidence of adenosine accumulation in group III
PH. A novel observation of our study was of evidence suggesting altered
mitochondrial metabolism in lung tissue from group III PH leading to increased
succinate levels that are able to further stabilize HIF-1A. Our data demonstrate
that the hypoxic-adenosine axis is up-regulated in group III PH and that
subsequent succinate accumulation may play a part in the development of group III
PH.
PMID- 26414705
TI - The potential for remote ischemic conditioning to improve outcomes in heart
failure.
AB - Heart failure is the end-stage of a variety of underlying cardiovascular diseases
and carries a poor prognosis. The condition is caused by a complex interaction
between many pathophysiological processes including ischemia, fibrosis,
ventricular remodeling, abnormal neurohumoral balance and inflammation. While
traditional pharmacological treatment of heart failure often targets only one
pathophysiological mechanism, remote ischemic conditioning induces a multitude of
cardioprotective effects. In particular, the anti-ischemic, anti-remodeling and
anti-inflammatory properties of remote ischemic conditioning may be of relevance.
We propose that remote ischemic conditioning may offer a novel strategy to
improve outcomes in heart failure.
PMID- 26414706
TI - Inflammatory Bowel Disease in Children and Adolescents.
AB - The inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn
disease, are chronic inflammatory disorders of the gastrointestinal tract most
often diagnosed in adolescence and young adulthood, with a rising incidence in
pediatric populations. These disorders are common enough in children that most
pediatricians and other pediatric clinicians will encounter children with IBD in
their general practice. Inflammatory bowel disease is caused by a dysregulated
mucosal immune response to the intestinal microflora in genetically predisposed
hosts. Although children can present with the classic symptoms of weight loss,
abdominal pain, and bloody diarrhea, many present with nonclassic symptoms of
isolated poor growth, anemia, or other extraintestinal manifestations. Once IBD
is diagnosed, the goals of therapy consist of eliminating symptoms, normalizing
quality of life, restoring growth, and preventing complications while minimizing
the adverse effects of medications. Unique considerations when treating children
and adolescents with IBD include attention to the effects of the disease on
growth and development, bone health, and psychosocial functioning. The purpose of
this review is to provide a contemporary overview of the epidemiologic features,
pathogenesis, diagnosis, and management of IBD in children and adolescents.
PMID- 26414707
TI - Autologous Bone Marrow Mononuclear Cells Exert Broad Effects on Short- and Long
Term Biological and Functional Outcomes in Rodents with Intracerebral Hemorrhage.
AB - Autologous bone marrow-derived mononuclear cells (MNCs) are a potential therapy
for ischemic stroke. However, the effect of MNCs in intracerebral hemorrhage
(ICH) has not been fully studied. In this study, we investigated the effects of
autologous MNCs in experimental ICH. ICH was induced by infusion of autologous
blood into the left striatum in young and aged male Long Evans rats. Twenty-four
hours after ICH, rats were randomized to receive an intravenous administration of
autologous MNCs (1 * 10(7) cells/kg) or saline. We examined brain water content,
various markers related to the integrity of the neurovascular unit and
inflammation, neurological deficit, neuroregeneration, and brain atrophy. We
found that MNC-treated young rats showed a reduction in the neurotrophil
infiltration, the number of inducible nitric oxide synthase-positive cells, and
the expression of inflammatory-related signalings such as the high-mobility group
protein box-1, S100 calcium binding protein B, matrix metalloproteinase-9, and
aquaporin 4. Ultimately, MNCs reduced brain edema in the perihematomal area
compared with saline-treated animals at 3 days after ICH. Moreover, MNCs
increased vessel density and migration of doublecortin-positive cells, improved
motor functional recovery, spatial learning, and memory impairment, and reduced
brain atrophy compared with saline-treated animals at 28 days after ICH. We also
found that MNCs reduced brain edema and brain atrophy and improved spatial
learning and memory in aged rats after ICH. We conclude that autologous MNCs can
be safely harvested and intravenously reinfused in rodent ICH and may improve
long-term structural and functional recovery after ICH. The results of this study
may be applicable when considering future clinical trials testing MNCs for ICH.
PMID- 26414708
TI - Receptor Protein Tyrosine Phosphatase alpha-Mediated Enhancement of Rheumatoid
Synovial Fibroblast Signaling and Promotion of Arthritis in Mice.
AB - OBJECTIVE: During rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS)
critically promote disease pathogenesis by aggressively invading the
extracellular matrix of the joint. The focal adhesion kinase (FAK) signaling
pathway is emerging as a contributor to the anomalous behavior of RA FLS. The
receptor protein tyrosine phosphatase alpha (RPTPalpha), which is encoded by the
PTPRA gene, is a key promoter of FAK signaling. The aim of this study was to
investigate whether RPTPalpha mediates FLS aggressiveness and RA pathogenesis.
METHODS: Through RPTPalpha knockdown, we assessed FLS gene expression by
quantitative polymerase chain reaction analysis and enzyme-linked immunosorbent
assay, invasion and migration by Transwell assays, survival by annexin V and
propidium iodide staining, adhesion and spreading by immunofluorescence
microscopy, and activation of signaling pathways by Western blotting of FLS
lysates. Arthritis development was examined in RPTPalpha-knockout (KO) mice using
the K/BxN serum-transfer model. The contribution of radiosensitive and
radioresistant cells to disease was evaluated by reciprocal bone marrow
transplantation. RESULTS: RPTPalpha was enriched in the RA synovial lining.
RPTPalpha knockdown impaired RA FLS survival, spreading, migration, invasiveness,
and responsiveness to platelet-derived growth factor, tumor necrosis factor, and
interleukin-1 stimulation. These phenotypes correlated with increased
phosphorylation of Src on inhibitory Y(527) and decreased phosphorylation of FAK
on stimulatory Y(397) . Treatment of RA FLS with an inhibitor of FAK phenocopied
the knockdown of RPTPalpha. RPTPalpha-KO mice were protected from arthritis
development, which was due to radioresistant cells. CONCLUSION: By regulating the
phosphorylation of Src and FAK, RPTPalpha mediates proinflammatory and
proinvasive signaling in RA FLS, correlating with the promotion of disease in an
FLS-dependent model of RA.
PMID- 26414709
TI - Heterotrimeric G proteins interact with defense-related receptor-like kinases in
Arabidopsis.
AB - Heterotrimeric G proteins (G-proteins) are versatile signaling elements conserved
in Eukaryotes. In animals G-proteins relay signals from 7-transmembrane spanning
G protein-coupled receptors (GPCRs) to intracellular downstream effectors;
however, the existence of GPCRs in plants is controversial. Contrastingly, a
surplus of receptor-like kinases (RLKs) provides signal recognition at the plant
cell surface. It is established that G proteins are involved in plant defense and
suggested that they relay signals from defense-related RLKs. However, it is
unclear how the signaling is conducted, as physical interaction between the RLKs
and G proteins has not been demonstrated. Using yeast split-ubiquitin system and
Bimolecular Fluorescence Complementation assays, we demonstrate physical
interaction between the Galpha, Ggamma1 and Ggamma2 subunits, and the defense
related RD-type receptor like kinases CERK1, BAK1 and BIR1. At the same time, no
interaction was detected with the non-RD RLK FLS2. We hypothesize that G-proteins
mediate signal transduction immediately downstream of the pathogenesis-related
RLKs.
PMID- 26414711
TI - Interstate Medical Licensure Compact: Pernicious Myths and Inescapable Facts.
PMID- 26414710
TI - Role of Osteogenesis in the Formation of Randall's Plaques.
PMID- 26414712
TI - Accuracy and Adequacy of Computed Tomography-Guided Lung Biopsies: Experience
From a Community Hospital.
AB - CONTEXT: Small tissue biopsies obtained through minimally invasive methods have
become the primary diagnostic tools for the pathologic characterization and
testing of lung masses. In view of recent advances in targeted therapy for non
small cell lung carcinoma, and lung adenocarcinoma in particular, pathologists
are now expected to thoroughly characterize lung lesions microscopically while
making certain that enough tissue remains for potential molecular analysis if
indicated. OBJECTIVE: To report our experience with computed tomography (CT)
guided lung needle biopsies with particular concentration on diagnostic yield,
diagnostic accuracy, and adequacy of tissue for molecular testing if indicated.
METHODS: A retrospective observational study analyzed 224 biopsies in 222
patients undergoing CT-guided lung needle biopsies. Accuracy of diagnosis and
adequacy of tissue for molecular testing, if applicable, was evaluated. A
standardized protocol for specimen evaluation, triage, and processing was used.
This protocol included intraprocedural real-time microscopic specimen evaluation
and triage by a pathologist and use of a histologic protocol specifically
designed to conserve tissue for ancillary testing. The initial biopsy was
considered successful if the specimen was malignant, had specific benign
features, or had nonspecific benign features with follow-up supporting benign
lesion. Initial biopsy failure cases were those with inadequate tissue or a
nonspecific result with highly suspicious imaging or clinical findings. RESULTS:
Of the 224 biopsies, 8 cases with benign but nonspecific findings lacked follow
up and were excluded from the study. The biopsy was diagnostically successful in
189 of 216 (88%) cases. Of these 189 cases, 154 (81%) were malignant, and 35
(19%) were benign. There were 28 diagnostic failures. Subsequent tissue sampling
of 13 of 28 diagnostic failures found 9 (69%) to be malignant. Molecular studies
were requested on 25 cases: 24 had sufficient material for some of the requested
tests, and 20 had enough tissue for all requested testing. CONCLUSION: A
standardized protocol and team approach for CT-guided lung needle biopsy
optimizes the ability to achieve a high accurate diagnostic yield with adequate
tissue for molecular testing.
PMID- 26414713
TI - Quantification of Motion Palpation.
AB - CONTEXT: The palpation of motions is at the heart of the practice of foreign
trained osteopaths. When practicing osteopathic manual therapy (care provided by
foreign-trained osteopaths) in the cranial field or osteopathic cranial
manipulative medicine, the palpation of small motions (several tens of
micrometers) is a key process. However, to the authors' knowledge, the smallest
detectable motion has not been identified. OBJECTIVE: To quantify motion
detection capacity by passive palpation. METHODS: Participants were instructed to
hold a mechanical device containing a micrometric actuator between their hands
and report when they felt motion while 6 series of 27 random motions were
generated by the actuator. After each series, if a participant succeeded or
failed to detect motion with a confidence level of greater than 98%, the motions
in the next series were set to a smaller or larger magnitude, respectively. After
6 series, the individual motion detection capacity was recorded. Statistical
significance was set at P=.02. RESULTS: A total of 21 participants were selected,
comprising 14 osteopaths and 7 nonosteopaths. The average performance of the
sample was 148 MUm. Thirteen participants (62%) perceived motions of 200 MUm or
less, and 7 participants (33%) detected motions of 50 MUm or less with bare
hands. Osteopathic training did not notably affect the performance. Osteopaths
were twice as likely to claim detection of nonexisting motions than to miss
existing ones, whereas nonosteopaths were equally subject to both types of
errors. CONCLUSION: The data show human passive palpatory sensitivity to be in
the range of several tens of micrometers. This range is comparable to that
reported for calvarial motion (10-50 MUm).
PMID- 26414715
TI - Peroneus Longus Rupture at Its Origin Managed With Platelet Rich Plasma.
AB - Tears of the peroneus longus muscle are unusual, and typically involve the distal
insertion at the musculotendon junction. Although tears of the mid-portion of the
peroneus longus muscle/tendon complex have been reported, no reports of a tear at
the origin of the peroneus muscle have been published, to the authors' knowledge.
Herein a case of proximal peroneus longus muscle tear and its subsequent
management with platelet rich plasma is reported.
PMID- 26414714
TI - Non-Vitamin K Antagonist Oral Anticoagulants: The Clinician's New Challenge.
AB - Millions of US patients are prescribed oral anticoagulants. Traditionally, oral
anticoagulation was achieved with vitamin K antagonists (VKAs). In recent years,
non-VKA oral anticoagulants (NOACs) have emerged that provide an effective and
convenient alternative to VKAs. These agents possess very different pharmacologic
properties from what the medical community has grown accustom to with the VKAs.
Thus, a new knowledge base is required for NOACs. One particular challenge with
the NOACs is the lack of specific reversal agent, resulting in difficulties
correcting the coagulopathy induced by these drugs when needed. A review of the
current literature is presented to assist clinicians in gaining knowledge of the
NOACs to care for patients.
PMID- 26414722
TI - Extensive Case of Subcutaneous Emphysema.
PMID- 26414723
TI - Filling an Open Spot.
PMID- 26414724
TI - Effects of Stem Cell Treatment in Human Patients With Peyronie Disease.
AB - CONTEXT: Peyronie disease (PD) is a connective tissue disorder involving the
formation of fibrous plaques in the tunica albuginea. Abnormal plaques and scar
tissue create a chronic state of inflammation, causing increased curvature of the
penis as well as erectile dysfunction. OBJECTIVE: To determine the feasibility
and effects of using placental matrix-derived mesenchymal stem cells (PM-MSCs) in
the management of PD. METHODS: In a prospective study, patients with PD were
injected with PM-MSCs, and followed up at 6-week, 3-month, and 6-month intervals
to assess changes in plaque volume, penile curvature, and erectile function
status (measured using peak systolic velocity, end-diastolic velocity, and the
International Index of Erectile Function questionnaire). RESULTS: In the 5
patients enrolled in the study, statistically significant increases in peak
systolic velocity occurred after PM-MSC injection (P<.01). Of a total of 10
plaques managed, 7 had disappeared completely at 3-month follow-up. Changes in
end-diastolic velocity, stretched penile length, and penile girth were not
statistically significant. CONCLUSION: To our knowledge, this study is the first
on the use of stem cells to manage PD in humans. The results suggest that PM-MSCs
may be beneficial and effective as a nonsurgical treatment in patients with PD.
Future studies with long-term follow-up in a larger sample of patients are
warranted. (ClinicalTrials.gov number NCT02395029).
PMID- 26414725
TI - The tumor-suppressive function of miR-1 by targeting LASP1 and TAGLN2 in
esophageal squamous cell carcinoma.
AB - OBJECTIVE: This study determined the expression of microRNA-1 in esophageal
squamous cell carcinoma (ESCC) tissue and cell lines to evaluate its effects on
clinicopathological parameters and its target genes LASP1 and TAGLN2. METHODS:
The expression of miR-1, lasp1, and tagln2 was detected in 55 ESCC tissues and
adjacent normal tissues by reverse transcription-polymerase chain reaction (RT
PCR). The association between miR-1, lasp1, and tagln2 expression and
clinicopathological characteristics was observed. MicroRNA-1 (mimics-miR-1) and
its inhibitor (Inhibitor-miR-1) were transfected into esophageal cancer cells
KYSE 510 and Eca 109; cell proliferation, migration, and invasion assays were
carried out. Plasmid construction and dual-luciferase reporter assay were also
carried out to indicate whether LASP1 and TAGLN2 were miR-1 target genes. The
expression of LASP1 and TAGLN2 was detected with Western blot methods in cell
lines, by immunohistochemistry in ESCC tissue. RESULTS: The gene expression level
of microRNA-1 in cancer tissues was significantly lower than that in adjacent
normal tissues (P < 0.01). The expression of miR-1 in ESCC was correlated with
involvement of lymph nodes (P = 0.002), histologic classification (P = 0.000),
and vessel invasion (P = 0.022). The expression of lasp1 and tagln2 increased in
cancer tissues compared with in adjacent normal tissues (P < 0.05). MiR-1
suppresses the cell growth, migration, and invasion in vitro. The expression of
LASP1 and TAGLN2 decreased in mimics-miR-1 transfected cells, and increased in
inhibitor-miR-1 transfected cells. Luciferase reporter assay confirmed that LASP1
and TAGLN2 mRNA actually had the target sites of miR-1. CONCLUSIONS: miR-1
suppresses cell proliferation, invasiveness, metastasis, and progression of ESCC
by binding its targeted genes LASP1 and TAGLN2.
PMID- 26414726
TI - Reply.
PMID- 26414727
TI - Editorial Comment.
PMID- 26414728
TI - Elucidation of Pyranonigrin Biosynthetic Pathway Reveals a Mode of Tetramic Acid,
Fused gamma-Pyrone, and exo-Methylene Formation.
AB - Successful activation of the pyranonigrin biosynthetic gene cluster and gene
knockout in Aspergillus niger plus in vivo and in vitro assays led to isolation
of six new products, including a spiro cyclobutane-containing dimeric compound,
which served as the basis for the proposed comprehensive pyranonigrin
biosynthetic pathway. Two redox enzymes are key to forming the characteristic
fused gamma-pyrone core, and a protease homologue performs the exo-methylene
formation.
PMID- 26414729
TI - The role of uric acid in the development of cardiovascular disease.
AB - The main purpose of the present supplement, which is based on a symposium held in
Bologna, 6-8 November 2014, is twofold: first of all, to reinforce the role of
uric acid in the pathogenesis of gout and gout-related non-rheumatic diseases
including renal involvement; second, to provide an updated review of the evidence
supporting the relevant role of elevated uric acid as a risk factor for
cardiovascular diseases.
PMID- 26414730
TI - Why focus on uric acid?
AB - In gouty patients, urate lowering therapies (ULTs) are recommended to bring serum
uric acid (SUA) levels below 6.0 mg/dL, with the aim of dissolving urate
depositions, thereby reducing disease impact. However, patients with
hyperuricemia often present with other conditions associated with cardiovascular
(CV) risk, such as high blood pressure, obesity, insulin resistance, fatty liver,
and chronic kidney disease. In the last decade, several well grounded pieces of
evidence showed that the elevation of uric acid often occurs prior to the
development of hypertension or metabolic syndrome, thus suggesting a direct
association between elevated SUA and these conditions. This paper will discuss
available evidence supporting the key role of serum uric acid in the development
of CV and renal disease, with a focus on the molecular mechanisms underlying this
causative association. This review is based on a PubMed/Embase database search
for articles on hyperuricemia and its impact on cardiovascular and renal
function.
PMID- 26414731
TI - Inflammation: a possible mechanism for a causative role of hyperuricemia/gout in
cardiovascular disease.
AB - Hyperuricemia and gout are independent risk factors associated with the
development of hypertension, metabolic syndrome, vascular damage, and renal
disease. Whether these risk factors are causally related to these important
chronic co-morbidities remains uncertain, but inflammation may provide a
mechanistic explanation. Hyperuricemia and gout negatively affect vascular
function by exerting pro-oxidant effects and by decreasing nitric oxide
bioavailability, thus inducing inflammation and endothelial dysfunction, which
may promote hypertension, metabolic syndrome, and cardiovascular (CV) disease.
This paper presents and discusses current understanding of the diverse influences
promoting hyperuricemia and gout and the basis of acute and chronic
hyperuricemia/gout-related inflammation. This review is based on a PubMed/Embase
database search for articles on hyperuricemia and its impact on cardiovascular
and renal function.
PMID- 26414732
TI - Hyperuricemia, urate deposition and the association with hypertension.
AB - Hyperuricemia is associated with hypertension, kidney disease, vascular and
cardiovascular (CV) events. In experimental models, the inhibition of hepatic
uricase induces hyperuricemia, hypertension and mild renal disease. Notably, the
micro- and macrovascular changes observed in the experimental model of
hyperuricemia resemble the histological changes of human hypertension. This paper
presents and discusses the epidemiological correlation between high serum uric
acid levels and hypertension, and reviews current evidence supporting the
protective effects of the normalization of uric acid levels. This review is based
on a PubMed/Embase database search for articles on hyperuricemia and its impact
on cardiovascular and renal function.
PMID- 26414733
TI - Detrimental role of hyperuricemia on the cardio-reno-vascular system.
AB - A bulk of evidence now exists that links gout with adverse cardiovascular (CV)
outcomes. However, continuing doubt remains as to whether hyperuricemia can be
truly considered an independent major CV risk factor. In fact, many gouty
patients who develop major CV and renal events also possess several traditional
CV risk factors, the presence of which can potentially confound any relationship
between gout and adverse CV events. This paper reviews the available evidence to
determine whether sufficient proof exists from biological, epidemiological and
clinical trial studies to support a causal relationship between gout and major CV
and renal events. This review is based on a PubMed/Embase database search for
articles on hyperuricemia and its impact on cardiovascular and renal function.
PMID- 26414734
TI - The management of hyperuricemia with urate deposition.
AB - Recent epidemiological data suggest a progressive increase of serum levels of
uric acid worldwide. This rise in the prevalence of hyperuricemia may be related
to the epidemic diffusion of overweight and obesity as well as the shifts in diet
with increased consumption of foods rich in purines, alcoholic consumption, and
soft drinks sweetened with fructose. The rise in serum uric acid levels worldwide
may be regarded as leading an increased risk for gout and other systemic
diseases, especially in the cardio-renal system. Therefore, careful management of
hyperuricemia with urate deposition is crucial to prevent or even treat those
systemic diseases. Despite this, hyperuricemia and gout often remain untreated.
This paper reviews current evidence on the management of hyperuricemia with urate
deposition, with a focus on its most controversial aspects. This review is based
on a PubMed/Embase database search for articles on hyperuricemia and its impact
on cardiovascular and renal function.
PMID- 26414736
TI - An Innovative Free-Hand Puncture Technique to Reduce Radiation in Percutaneous
Nephrolithotomy Using Ultrasound with Navigation System Under Magnetic Field: A
Single-Center Experience in Hong Kong.
AB - OBJECTIVE: Traditionally, fluoroscopy or ultrasound (US) or both are used for
guiding tract creation during percutaneous nephrolithotomy (PCNL). However, the
use of fluoroscopy inevitably incurs radiation exposure, which should be cut down
as much as possible in view of its potential adverse effects on health: both
deterministic effects and stochastic effects. Conventional US guidance, being
radiation free, can serve the purpose, but it is difficult to visualize the
needle tract during screening without a needle-guiding system fixed to the
transducer, and hence, there is a lack of predictability and sense of security.
The objective of this study is to assess the feasibility of using US with
navigation system (USNS) to solve the above problems. PATIENTS AND METHODS: In
2014, we performed PCNL on 18 patients with USNS guidance. During the puncture
step, the magnetic field-based navigation US could help visualize the position of
the needle tract in relation to the target calix. The procedure was done in free
hand without the usage of needle-guiding system attached to the transducer.
Needle deviation could be detected and adjusted immediately to achieve precise
puncture. RESULTS: Of the 18 patients, 83.3% (15/18) of them had their punctures
effectively done with a single attempt. Three puncture procedures were performed
by two urologic trainees without any previous USNS experience. The mean
fluoroscopy time during dilatation was 74.6s, with no radiation at all during the
puncture step. The stone clearance rate was 72.2%, with 66.7% (12/18) being
tubeless procedures. The mean length of hospital stay was 4.8 days. No immediate
complications related to the puncture procedure were found. CONCLUSIONS: USNS can
provide radiation-free guidance for tract creation in PCNL. It is predictable,
precise, reliable, and safe. Most importantly, the technique is easy to learn,
particularly for urologists who are new to PCNL.
PMID- 26414735
TI - Chronic Effects of Boxing: Diffusion Tensor Imaging and Cognitive Findings.
AB - We used magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to
evaluate the effects of boxing on brain structure and cognition in 10 boxers (8
retired, 2 active; mean age = 45.7 years; standard deviation [SD] = 9.71) and 9
participants (mean age = 43.44; SD = 9.11) in noncombative sports. Evans Index
(maximum width of the anterior horns of the lateral ventricles/maximal width of
the internal diameter of the skull) was significantly larger in the boxers (F =
4.52; p = 0.050; Cohen's f = 0.531). Word list recall was impaired in the boxers
(F(1,14) = 10.70; p = 0.006; f = 0.84), whereas implicit memory measured by
faster reaction time (RT) to a repeating sequence of numbers than to a random
sequence was preserved (t = 2.52; p < 0.04). Fractional anisotropy (FA) and the
apparent diffusion coefficient (ADC) measured by tractography did not
significantly differ between groups. However, DTI metrics were significantly
correlated with declarative memory (e.g., left ventral striatum ADC with delayed
recall, r = -0.74; p = 0.02) and with RT to the repeating number sequence (r =
0.70; p = 0.04) in the boxers. Years of boxing had the most consistent, negative
correlations with FA, ranging from -0.65 for the right ventral striatum to -0.92
for the right cerebral peduncle. Years of boxing was negatively related to the
number of words consistently recalled over trials (r = -0.74; p = 0.02), delayed
recall (r = -0.83; p = 0.003), and serial RT (r = 0.66; p = 0.05). We conclude
that microstructural integrity of white matter tracts is related to declarative
memory and response speed in boxers and to the extent of boxing exposure.
Implications for chronic traumatic encephalopathy are discussed.
PMID- 26414737
TI - Effect of dispersants on the biodegradation of South Louisiana crude oil at 5 and
25 degrees C.
AB - This article reports biodegradation rates for a commercial dispersant, JD-2000,
South Louisiana crude oil (SLC) alone, and SLC dispersed with JD-2000 at 5 and 25
degrees C. Results from the biodegradation experiments revealed that Component
X, a chemical marker for JD-2000, rapidly degraded at both temperatures. The
application of JD-2000 decreased by half the overall biodegradation rate of
aliphatic compounds at 25 degrees C. At 5 degrees C, a residual fraction
consisting of iso- and n-alkanes (C29-C35) persisted after 56 d. The combination
of dispersant and higher temperature resulted in faster removal rates for 2- and
3-ring polycyclic aromatic hydrocarbons. When compared with Corexit 9500, our
results suggest that the chemistry of the surfactant (or surfactants) in JD-2000
might have favored oil dissolution (substrate transport to the aqueous phase) as
an uptake mechanism over adhesion, which requires direct contact of the biomass
with the oil.
PMID- 26414738
TI - Subchronic exposure to chlorpyrifos affects energy expenditure and detoxification
capacity in juvenile Japanese quails.
AB - Effects of pesticides on non-target organisms have been studied in several taxa
at different levels of biological organization, from enzymatic to behavioral
responses. Although the physiological responses may be associated with higher
energy costs, little is known about metabolic costs of pesticide detoxification
in birds. To fill this gap, we exposed orally (diet) 15-d old Coturnix coturnix
japonica individuals to sublethal doses of chlorpyrifos (10 and 20 mg active
ingredient/kg dry food) for four weeks. Carboxylesterase (CbE),
butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) activities were
periodically measured in multiple tissues along with measurements of resting
(RMR) and maximum metabolic rates (M(sum)). Furthermore, glucuronic acid in bird
excreta was also assessed at the end of the trial. While CbE and BChE activities
were inhibited by chlorpyrifos in all tissues during the third and fourth weeks
following pesticide treatment, AChE activity was unaffected. At this sampling
times, both M(sum) and RMR expansibility decreased. These results suggest that
the exposure to chlorpyrifos caused a negative effect on aerobic performance.
Additionally, excretion rate of glucuronic acid was up to 2-fold higher in the 20
mg/kg group than in the control and 10-mg/kg chlorpyrifos groups. The inhibition
of CbE and BChE activities corroborated that these enzymes are fulfilling their
role as bioscavengers for organophosphate pesticides, decreasing its
concentration and thus protecting AChE activity against inhibition by
chlorpyrifos.
PMID- 26414739
TI - Vicia faba bioassay for environmental toxicity monitoring: A review.
AB - Higher plants are recognized as excellent genetic models to detect cytogenetic
and mutagenic agents and are frequently used in environmental monitoring studies.
Vicia faba (V. faba) bioassay have been used to study DNA damages i.e.,
chromosomal and nuclear aberrations induced by metallic compounds, pesticides,
complex mixtures, petroleum derivates, toxins, nanoparticles and industrial
effluents. The main advantages of using V. faba is its availability round the
year, economical to use, easy to grow and handle; its use does not require
sterile conditions, rate of cell division is fast, chromosomes are easy to score,
less expensive and more sensitive as compared to other short-term tests that
require pre-preparations. The V. faba test offers evaluation of different
endpoints and tested agents can be classified as cytotoxic/genotoxic/mutagenic.
This test also provides understanding about mechanism of action, whether the
tested agent is clastogenic or aneugenic in nature. In view of advantages offered
by V. faba test system, it is used extensively to assess toxic agents and has
been emerged as an important bioassay for ecotoxicological studies. Based on the
applications of V. faba test to assess the environmental quality, this article
offers an overview of this test system and its efficiency in assessing the
cytogenetic and mutagenic agents in different classes of the environmental
concerns.
PMID- 26414740
TI - A large-scale model for simulating the fate & transport of organic contaminants
in river basins.
AB - We present STREAM-EU (Spatially and Temporally Resolved Exposure Assessment Model
for EUropean basins), a novel dynamic mass balance model for predicting the
environmental fate of organic contaminants in river basins. STREAM-EU goes beyond
the current state-of-the-science in that it can simulate spatially and temporally
resolved contaminant concentrations in all relevant environmental media (surface
water, groundwater, snow, soil and sediments) at the river basin scale. The model
can currently be applied to multiple organic contaminants in any river basin in
Europe, but the model framework is adaptable to any river basin in any continent.
We simulate the environmental fate of perfluoroctanesulfonic acid (PFOS) and
perfluorooctanoic acid (PFOA) in the Danube River basin and compare model
predictions to recent monitoring data. The model predicts PFOS and PFOA
concentrations that agree well with measured concentrations for large stretches
of the river. Disagreements between the model predictions and measurements in
some river sections are shown to be useful indicators of unknown contamination
sources to the river basin.
PMID- 26414741
TI - Engineering of a highly efficient Xe2*-excilamp (xenon excimer lamp,
lambdamax=172 nm, eta=40%) and qualitative comparison to a low-pressure mercury
lamp (LP-Hg, lambda=185/254 nm) for water purification.
AB - Excilamps are mercury-free gas-discharge sources of non-coherent VUV or UV
radiation with high radiant power and a long lifetime. The most efficient
excilamp that is currently available on the market is a VUV xenon excilamp system
(Xe2(*)-excimer lamp, lambda(max) = 172 nm) with a stated radiant efficiency eta
of 40% at an electrical input power P(el) of 20 W, 50 W or 100 W. In this paper,
the use of this highly efficient Xe2(*)-excilamp (P(el) = 20 W) for water
treatment is demonstrated using a recirculating laboratory photoreactor system
with negative radiation geometry. The efficiency in the 172 nm initiated
bleaching of aqueous solutions of Rhodamine B is compared to that initiated by a
common low-pressure mercury (LP-Hg) lamp (185 nm, TNN 15/32). The dependence of
the pseudo zero order rate constant k' of decolorization of RhB on the flow rate
and on the initial concentration of RhB was investigated. Both lamps exhibited
dependences of k' on the initial concentration of RhB, which represents a typical
saturation kinetical behavior. The saturation kinetics was very prominent in the
case of the Xe2(*)-excilamp. Also, the Xe2(*)-excilamp treatment exhibited a
significant influence on the flow rate of the RhB aqueous solution, which was not
the case during the LP-Hg lamp initiated bleaching of RhB. The results of this
paper demonstrate that Xe2(*)-excilamps can be used for VUV-initiated water
purification. However, to reach the maximum efficacy of the Xe2(*)-excilamp for
photo-initiated water purification further engineering optimization of the
photoreactor concept is necessary.
PMID- 26414742
TI - Photodegradation of dissolved organic matter in ice under solar irradiation.
AB - The photodegradation behavior of dissolved organic matter (DOM) with different
origins in ice under solar irradiation was investigated. Exposure to sunlight at
2.7 * 10(5) J m(-2) resulted in dissolved organic carbon (DOC) reductions of 22.1
36.5% in ice. The naturally occurring DOM had higher photodegradation potentials
than the wastewater-derived DOM in ice. Ultraviolet (UV)-absorbing compounds in
DOM, regardless of DOM origin, had much higher photodegradation potentials than
gross DOC in ice. The susceptibility of UV-absorbing compounds with natural
origin to sunlight exposure in ice was higher than those derived from wastewater.
Trihalomethane (THM) precursors were more susceptible to photochemical reactions
than gross DOC and haloacetic acid (HAA) precursors in ice. THM precursors in
naturally occurring DOM were more photoreactive than those in wastewater-derived
DOM in ice, while the photoreactivity of HAA precursors in ice was independent of
DOM origin. In ice, the photoreactivity of humic-like fluorescent materials,
regardless of DOM origin, was higher than that of gross DOC and protein-like
fluorescent materials. DOC reductions caused by sunlight irradiation were found
to be negatively correlated to DOC levels, and positively correlated to the
aromaticity of DOM. The photodegradation of both wastewater-derived and naturally
occurring DOM in ice was significantly facilitated at both acid and alkaline pH,
as compared to neutral pH. The photodegradation of DOM in ice, regardless of the
origin, was facilitated by nitrate ion [Formula: see text] , nitrite ion
[Formula: see text] , ferric ion (Fe(3+)) and ferrous ion (Fe(2+)), and on the
other hand, was inhibited by chloridion ion (Cl(-)) and copper ion (Cu(2+)).
PMID- 26414744
TI - Assistive technology use by disability type and race: exploration of a population
based health survey.
AB - PURPOSE: To examine the relationships among Assistive Technology (AT) use, race,
type of disability and selected other demographic characteristics. METHOD: Using
2009 National Health Interview Survey, descriptive statistics, statistical
interactions and binary logistic regression were performed to identify, contrast
and predict the likelihood of using AT based on the type of disability among
African Americans (AAs) and European Americans (EAs). RESULTS: We found that more
AAs (10% within group proportion of total AAs) used AT compared to EAs (7.5%
within group proportion of total EAs). Physical (p < 0.001), auditory (p = 0.028)
and emotional (p = 0.008) impairments were statistically significant predictors
of AT use. However, physical impairment as a predictor of AT use was greater
among AAs (OR = 222.49, CI: 64.04-773.04, p < 0.001) than EAs (OR = 50.77, CI:
31.78-81.12, p < 0.001). EAs had a greater number of disabling conditions that
predict the use of AT than AAs, whereas AAs had more demographic characteristics
beyond race that predict AT use than EAs. CONCLUSIONS: Disparities were observed
in AT usage by disability types and demographic characteristics between AAs and
EAs. Moreover, the predictive strength of AT usage based on disability types and
other demographic variables differed by races. Overall, the findings about the
different relationships among race, disability type, and AT use are found.
Implications for Rehabilitation The finding may inform the development of
initiatives by rehabilitation leaders to encourage the use of AT by AAs and EAs
according to their type of impairment. Having identified physical impairment as
statistically significant predictor of AT use greater among AAs, rehabilitation
leaders should ensure that people living with those types of disability have
access to the corresponding type of AT and can use them effectively.
PMID- 26414743
TI - A Clinical Framework to Facilitate Risk Stratification When Considering an Active
Surveillance Alternative to Immediate Biopsy and Surgery in Papillary
Microcarcinoma.
AB - BACKGROUND: The 2015 American Thyroid Association thyroid cancer management
guidelines endorse an active surveillance management approach as an alternative
to immediate biopsy and surgery in subcentimeter thyroid nodules with highly
suspicious ultrasonographic characteristics and in cytologically confirmed very
low risk papillary thyroid cancer (PTC). However, the guidelines provide no
specific recommendations with regard to the optimal selection of patients for an
active surveillance management approach. This article describes a risk-stratified
clinical decision-making framework that was developed by the thyroid cancer
disease management team at Memorial Sloan Kettering Cancer Center as the lessons
learned from Kuma Hospital in Japan were applied to a cohort of patients with
probable or proven papillary microcarcinoma (PMC) who were being evaluated for an
active surveillance management approach in the United States. SUMMARY: A risk
stratified approach to the evaluation of patients with probable or proven PMC
being considered for an active surveillance management approach requires an
evaluation of three interrelated but distinct domains: (i) tumor/neck ultrasound
characteristics (e.g., size of the primary tumor, the location of the tumor
within the thyroid gland); (ii) patient characteristics (e.g., age,
comorbidities, willingness to accept observation); and (iii) medical team
characteristics (e.g., availability and experience of the multidisciplinary
team). Based on an analysis of the critical factors within each of these domains,
patients with probable or proven PTC can then be classified as ideal,
appropriate, or inappropriate candidates for active surveillance. CONCLUSION:
Risk stratification utilizing the proposed decision-making framework will improve
the ability of clinicians to recognize individual patients with proven or
probable PMC who are most likely to benefit from an active surveillance
management option while at the same time identifying patients with proven or
probable PMC that would be better served with an upfront biopsy and surgical
management approach.
PMID- 26414745
TI - MRI and planimetric CT follow-up study of patients with severe tick-borne
encephalitis.
AB - BACKGROUND: The aim of the study was to evaluate the magnetic resonance imaging
(MRI) and planimetric computed tomography (CT) of brain lesions in patients with
a history of tick-borne encephalitis (TBE); to assess the influence of steroid
treatment on the brain and whether lesions were age-dependent. METHODS: A total
of 19 patients with abnormal initial imaging in the acute stage of the disease
had a follow-up MRI after 1 year; 34 patients hospitalized for TBE
encephalitis/encephalomyelitis had planimetric CT after 10 years. RESULTS: On MRI
cortico-subcortical atrophy with widening of anterior horns of the lateral
ventricles and vascular changes was more marked on follow-up examination. Virchow
Robin spaces dilatation, widening of the lateral ventricles, periventricular
lesions, and cortico-subcortical atrophy correlated with age. Results of
planimetric CT study showed increased percentage of tracings, widened anterior
horns, lateral ventricles, and III ventricle, which suggest new non-age-related
atrophic lesions. CONCLUSIONS: Radiological lesions in the acute phase of TBE and
after recovery are non-specific. Cortico-subcortical atrophy with widening of the
anterior horns of the lateral ventricles and vascular changes are most common.
Long-term follow-up confirms the formation of new non-age-related cerebral
atrophic lesions due to TBE. The logit model may serve as a background for the
hypothesis concerning an accelerated local atrophy of the brain tissues in
patients with a history of severe TBE.
PMID- 26414746
TI - Automatic Control of Gene Expression in Mammalian Cells.
AB - Automatic control of gene expression in living cells is paramount importance to
characterize both endogenous gene regulatory networks and synthetic circuits. In
addition, such a technology can be used to maintain the expression of synthetic
circuit components in an optimal range in order to ensure reliable performance.
Here we present a microfluidics-based method to automatically control gene
expression from the tetracycline-inducible promoter in mammalian cells in real
time. Our approach is based on the negative-feedback control engineering
paradigm. We validated our method in a monoclonal population of cells
constitutively expressing a fluorescent reporter protein (d2EYFP) downstream of a
minimal CMV promoter with seven tet-responsive operator motifs (CMV-TET). These
cells also constitutively express the tetracycline transactivator protein (tTA).
In cells grown in standard growth medium, tTA is able to bind the CMV-TET
promoter, causing d2EYFP to be maximally expressed. Upon addition of tetracycline
to the culture medium, tTA detaches from the CMV-TET promoter, thus preventing
d2EYFP expression. We tested two different model-independent control algorithms
(relay and proportional-integral (PI)) to force a monoclonal population of cells
to express an intermediate level of d2EYFP equal to 50% of its maximum expression
level for up to 3500 min. The control input is either tetracycline-rich or
standard growth medium. We demonstrated that both the relay and PI controllers
can regulate gene expression at the desired level, despite oscillations (dampened
in the case of the PI controller) around the chosen set point.
PMID- 26414747
TI - A brief intervention for posttraumatic stress disorder in persons with a serious
mental illness.
AB - OBJECTIVE: Posttraumatic stress disorder (PTSD) is common in people with a
serious mental illness, but it is often not diagnosed or treated. Recent progress
has been made in developing and validating interventions for PTSD in this
population, but dropout from treatment can be problematic. The present study
evaluated the feasibility and clinical outcomes of a Brief program (three
sessions) for the treatment of PTSD in persons with a serious mental illness.
METHOD: An open clinical trial was conducted to evaluate the Brief program, which
comprises three individual weekly sessions and includes education about trauma
and PTSD, as well as instruction in breathing retraining for the self-management
of anxiety. Eighteen predominantly minority persons with serious mental illness
and PTSD were enrolled in the Brief program and assessed at baseline, 1-month
posttreatment, and 3-month follow-up. RESULTS: Acceptability and tolerability of
the program were high, with 15 of 18 (83%) study participants completing all
three sessions. Interview-based and self-report assessments indicated significant
reductions in PTSD symptoms, depression, and other symptoms at posttreatment,
with treatment gains maintained at the 3-month follow-up. CONCLUSION AND
IMPLICATION FOR PRACTICE: The results suggest the Brief program may be clinically
beneficial to persons with serious mental illnesses and PTSD and indicate that
more rigorous research is needed to evaluate the program.
PMID- 26414748
TI - Getting by, getting back, and getting on: Matching mental health services to
consumers' recovery goals.
AB - OBJECTIVE: The goal of this study was to better understand mental health recovery
from the point of view of mental health consumers to identify opportunities for
practice improvements that closely align services with consumer goals and
consumer-preferred outcomes. METHOD: As part of an exploratory study of recovery,
semistructured interviews were conducted with 177 integrated health plan members
diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder, or
affective psychosis. Transcripts of in-depth interviews were coded using
Atlas.ti, and definitions of recovery were further subcoded. A qualitative
analysis using a modified grounded theory approach and constant comparative
method identified common themes and less common but potentially important
recovery-related experiences and perspectives. RESULTS: Three primary and 2 cross
cutting themes emerged. "Getting by" meant coping and meeting basic needs.
"Getting back" meant learning to live with mental illness. "Getting on" meant
living a life where mental illness was no longer prominent. Regaining control and
recouping losses were cross-cutting themes. CONCLUSIONS/IMPLICATIONS FOR
PRACTICE: Mental health recovery is complex and dynamic; individuals' recovery
goals can be expected to change over time. Person-centered care must accommodate
changing consumer priorities, services must be flexible and responsive, and
outcomes need to match consumers' objectives. Clinicians can assist in (a)
identifying recovery goals, (b) monitoring progress toward and recognizing
movement away from goals, (c) tailoring support to different phases/stages, and
(d) supporting transitions between phases/stages. (PsycINFO Database Record
PMID- 26414750
TI - A palladium-catalyzed tandem reaction of 2-(2-bromobenzylidene)cyclobutanone with
2-alkynylphenol.
AB - An efficient approach for the generation of benzo[b]naphtho[2,3-d]oxocin-6-ones
through a palladium-catalyzed tandem reaction of 2-alkynylphenol with 2-(2
bromobenzylidene)cyclobutanone is described. This tandem process afforded the
fused polycycles easily, with the formation of three bonds with high efficiency,
starting from easily available materials. Good functional group tolerance as well
as excellent selectivity was displayed.
PMID- 26414749
TI - Job satisfaction of Department of Veterans Affairs peer mental health providers.
AB - OBJECTIVES: Department of Veterans Affairs (VA) peer specialists and vocational
rehabilitation specialists are Veterans employed in mental health services to
help other Veterans with similar histories and experiences. Study objectives were
to (a) examine job satisfaction among these employees, (b) compare them to other
VA mental health workers, and (c) identify factors associated with job
satisfaction across the 3 cohorts. METHODS: The study sample included 152 VA
employed peer specialists and 222 vocational rehabilitation specialists. A
comparison group included 460 VA employees from the same job categories. All
participants completed the Job Satisfaction Index (11 aspects and overall
satisfaction ratings). Linear regression was used to compare job satisfaction and
identify its predictors among the 3 cohorts. RESULTS: Job satisfaction was fairly
high, averaging "somewhat satisfied" to "very satisfied" in 6 (peer specialists)
and 9 (vocational rehabilitation specialists) of the 11 aspects and overall job
ratings. Adjusting for length of employment, age and gender resulted in no
significant group differences with 2 exceptions: White peer specialists were less
satisfied with pay and promotion opportunities than vocational rehabilitation
specialists and comparison-group employees. Across all cohorts, shorter length of
time employed in the job was associated with higher job satisfaction. CONCLUSIONS
AND IMPLICATIONS FOR PRACTICE: The high job satisfaction levels among the 2 peer
cohorts suggest support for the policy of hiring peer specialists in the VA.
Furthermore, the results are consistent with those of the nonveteran samples,
indicating that integrating peer providers into mental health care is possible in
VA and non-VA settings.
PMID- 26414752
TI - Human hepatic ductal plate malformation-like features are seen in a variety of
human postnatal nonhepatobiliary tissues.
PMID- 26414751
TI - Plasma Cytokine Levels in Chronic Asymptomatic HIV-1 Subtype C Infection as an
Indicator of Disease Progression in Botswana: A Retrospective Case Control Study.
AB - HIV infects cells of the immune system causing immune activation and
proliferation of immune cells, leading to alteration of production and activity
of a number of cytokines. These changes in cytokine levels can affect the immune
function, and have the potential to directly impact the course of HIV disease. We
characterized plasma cytokine concentration profiles in HIV-1 subtype C
chronically infected, antiretroviral therapy (ART)-naive participants to
establish their influence on disease progression and viremia. Plasma levels of
interleukin (IL)-1alpha, IL-7, IL-12p40, granulocyte macrophage-colony
stimulating factor (GM-CSF), and interferon (IFN)-gamma were quantified in
samples from 60 treatment-naive participants in the placebo arm of the completed
Micronutrient-HIV disease progressions study, "Dikotlana" (2004-2009) in
Gaborone, Botswana. Participants were stratified into progressors (P) and
nonprogressors (NP) based on their rates of CD4(+) T cell depletion during the
study period. Nonprogressors were those who had <1% CD4(+) T cell depletion at 24
months postenrollment. Progressors were defined as those with CD4(+) T cell
depletion of >15% at 24 months postenrollment. Cytokine levels were compared
between P and NP using the Mann-Whitney U-test. Logistic regression analysis was
used to determine if cytokines predicted disease progression. Correlations of
cytokines with CD4(+) T cell counts and viral loads were determined by the
Spearman rank test. Median baseline CD4(+) T cell counts were 453 (Q1, Q3; 401,
592) and 479 (Q1, Q3; 401-592) for nonprogressors and progressors, respectively.
Nonprogressors had a higher viral set point than progressors. IL-12p40 levels
were significantly higher in the P than in NP at enrollment and 24 months (p <
0.05). Levels of IL-1alpha, IL-7, IFN-gamma, and GM-CSF did not differ
significantly between the two groups. Except for IL-12p40, which displayed an
inverse correlation with CD4(+) T cell counts and a direct correlation with viral
load, all other cytokines showed no correlations. IL-12p40 was found to be the
most significant predictor of progression and its production was most likely
driven by HIV replication products as evidenced by its direct correlation with
viral load. In chronic HIV-1 subtype C infection, CD4(+) T cell counts and plasma
cytokine levels may not necessarily evolve in parallel, suggesting the
involvement of other factors in determining the rates of CD4(+) T cell depletion.
PMID- 26414754
TI - Turning Radiotherapy into an Effective Systemic Anti-cancer Treatment in
Combination with Immunotherapy.
PMID- 26414755
TI - Preface to the special issue on evolution and morphological diversity.
PMID- 26414757
TI - Quantitative susceptibility mapping using a superposed dipole inversion method:
Application to intracranial hemorrhage.
AB - PURPOSE: To investigate gradient-echo phase errors caused by intracranial
hemorrhage (ICH) of low signal magnitude, and propose methods to reduce artifacts
from phase errors in quantitative susceptibility mapping (QSM) of ICH. METHODS:
Two QSM methods are proposed: (1) mask-inversion that masks the phase of low
signal magnitude regions, and (2) ICH magnetic dipole field isolation followed by
susceptibility superposition using multiple boundaries for background field
removal. The reconstruction methods were tested in eight subjects with ICH using
standard single-echo susceptibility-weighted imaging at 1.5 Tesla with 40 ms echo
time. Different phase unwrapping algorithms were also compared. RESULTS:
Significant phase errors were evident inside ICHs with low signal magnitude. The
mask-inversion method recovered susceptibility of ICH in numerical simulation and
minimized phase error propagation in patients with ICH. The additional superposed
dipole inversion process substantially suppressed and constrained streaking
artifacts in all subjects. Using the proposed superposition method, ICH
susceptibilities measured from long and short echo times were similar. Laplacian
based phase unwrapping substantially underestimated the ICH dipole field as
compared to a path-based method. CONCLUSION: The proposed methods of mask
inversion as well as ICH isolation and superposition can substantially reduce
artifacts in QSM of ICH. Magn Reson Med 76:781-791, 2016. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26414758
TI - Production Task Queue Optimization Based on Multi-Attribute Evaluation for
Complex Product Assembly Workshop.
AB - The production task queue has a great significance for manufacturing resource
allocation and scheduling decision. Man-made qualitative queue optimization
method has a poor effect and makes the application difficult. A production task
queue optimization method is proposed based on multi-attribute evaluation.
According to the task attributes, the hierarchical multi-attribute model is
established and the indicator quantization methods are given. To calculate the
objective indicator weight, criteria importance through intercriteria correlation
(CRITIC) is selected from three usual methods. To calculate the subjective
indicator weight, BP neural network is used to determine the judge importance
degree, and then the trapezoid fuzzy scale-rough AHP considering the judge
importance degree is put forward. The balanced weight, which integrates the
objective weight and the subjective weight, is calculated base on multi-weight
contribution balance model. The technique for order preference by similarity to
an ideal solution (TOPSIS) improved by replacing Euclidean distance with relative
entropy distance is used to sequence the tasks and optimize the queue by the
weighted indicator value. A case study is given to illustrate its correctness and
feasibility.
PMID- 26414760
TI - Large animal models of atherosclerosis--new tools for persistent problems in
cardiovascular medicine.
AB - Coronary heart disease and ischaemic stroke caused by atherosclerosis are leading
causes of illness and death worldwide. Small animal models have provided insight
into the fundamental mechanisms driving early atherosclerosis, but it is
increasingly clear that new strategies and research tools are needed to translate
these discoveries into improved prevention and treatment of symptomatic
atherosclerosis in humans. Key challenges include better understanding of
processes in late atherosclerosis, factors affecting atherosclerosis in the
coronary bed, and the development of reliable imaging biomarker tools for risk
stratification and monitoring of drug effects in humans. Efficient large animal
models of atherosclerosis may help tackle these problems. Recent years have seen
tremendous advances in gene-editing tools for large animals. This has made it
possible to create gene-modified minipigs that develop atherosclerosis with many
similarities to humans in terms of predilection for lesion sites and
histopathology. Together with existing porcine models of atherosclerosis that are
based on spontaneous mutations or severe diabetes, such models open new avenues
for translational research in atherosclerosis. In this review, we discuss the
merits of different animal models of atherosclerosis and give examples of
important research problems where porcine models could prove pivotal for
progress.
PMID- 26414759
TI - Cognitive Behavior Therapy for Depression and Self-Care in Heart Failure
Patients: A Randomized Clinical Trial.
AB - IMPORTANCE: Depression and inadequate self-care are common and interrelated
problems that increase the risks of hospitalization and mortality in patients
with heart failure (HF). OBJECTIVE: To determine the efficacy of an integrative
cognitive behavior therapy (CBT) intervention for depression and HF self-care.
DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial with single-blind
outcome assessments. Eligible patients were enrolled at Washington University
Medical Center in St Louis between January 4, 2010, and June 28, 2013. The
primary data analyses were conducted in February 2015. The participants were 158
outpatients in New York Heart Association Class I, II, and III heart failure with
comorbid major depression. INTERVENTIONS: Cognitive behavior therapy delivered by
experienced therapists plus usual care (UC), or UC alone. Usual care was enhanced
in both groups with a structured HF education program delivered by a cardiac
nurse. MAIN OUTCOMES AND MEASURES: The primary outcome was severity of depression
at 6 months as measured by the Beck Depression Inventory. The Self-Care of Heart
Failure Index Confidence and Maintenance subscales were coprimary outcomes.
Secondary outcomes included measures of anxiety, depression, physical
functioning, fatigue, social roles and activities, and quality of life.
Hospitalizations and deaths were exploratory outcomes. RESULTS: One hundred fifty
eight patients were randomized to UC (n = 79) or CBT (n = 79). Within each arm,
26 (33%) of the patients were taking an antidepressant at baseline. One hundred
thirty-two (84%) of the participants completed the 6-month posttreatment
assessments; 60 (76%) of the UC and 58 (73%) of the CBT participants completed
every follow-up assessment (P = .88). Six-month depression scores were lower in
the CBT than the UC arm on the Beck Depression Inventory (BDI-II) (12.8 [10.6] vs
17.3 [10.7]; P = .008). Remission rates differed on the BDI-II (46% vs 19%;
number needed to treat [NNT] = 3.76; 95% CI, 3.62-3.90; P < .001) and the
Hamilton Depression Scale (51% vs 20%; NNT = 3.29; 95% CI, 3.15-3.43; P < .001).
The groups did not differ on the Self-Care Maintenance or Confidence subscales.
The mean (SD) Beck Depression Inventory scores 6 months after randomization were
lower in the CBT (12.8 [10.6]) than the UC arm (17.3 [10.7]), P = .008. There
were no statistically significant differences between the groups on the Self-Care
Maintenance or Confidence subscale scores or on physical functioning measures.
Anxiety and fatigue scores were lower and mental- and HF-related quality of life
and social functioning scores were higher at 6 months in the CBT than the UC arm,
and there were fewer hospitalizations in the intervention than the UC arm.
CONCLUSIONS AND RELEVANCE: A CBT intervention that targets both depression and
heart failure self-care is effective for depression but not for HF self-care or
physical functioning relative to enhanced UC. Additional benefits include reduced
anxiety and fatigue, improved social functioning, and better health-related
quality of life. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01028625.
PMID- 26414762
TI - Acne scarring: A review of available therapeutic lasers.
AB - BACKGROUND AND OBJECTIVE: The utilization of lasers in dermatology has greatly
expanded in recent decades. Acne scarring is a common indication in which lasers
play an important therapeutic role. STUDY DESIGN/MATERIALS AND METHODS: Available
lasers include traditional ablative lasers, such as carbon dioxide and erbium
lasers, traditional non-ablative lasers, such as neodymium, diode, alexandrite,
pulsed dye lasers and intense pulse light, as well as both ablative, and non
ablative fractional laser systems. CONCLUSION: We sought to provide a framework
for understanding the various types of lasers available to treat acne scars and
review the primary literature pertaining to the efficacy, safety, and advantages
of each laser discussed.
PMID- 26414761
TI - Black Cohosh Ameliorates Metabolic Disorders in Female Ovariectomized Rats.
AB - Estrogen deficiency is associated with metabolic derangements in menopausal
women. Black cohosh has been widely used as an alternative therapy in the
treatment of menopausal syndrome. However, its role in metabolism needs to be
defined. The aim of the present study was to investigate the long-term effect of
black cohosh on glucose and lipid metabolism in a rat model of post-menopause.
Adult female Sprague-Dawley rats were sham operated (SHAM), ovariectomized (OVX),
OVX with the treatment of estradiol valerate (OVX + E), or OVX with the treatment
of isopropanolic black cohosh extract (OVX + iCR). Body weight, body composition,
and blood glucose levels of the animals were monitored. The rats were then
sacrificed after 3 months of the treatments. At the end of the experiment, OVX +
iCR and OVX + E rats exhibited a significant decrease in body weight gain, body
and abdominal fat mass, serum triglycerides levels, hepatic fat accumulation, and
adipocyte hypertrophy compared with OVX rats. In addition, insulin resistance and
glucose intolerance were improved in OVX + iCR but not in OVX + E rats. No
hepatotoxicity was detected in OVX + iCR animals. Furthermore, western blot
analysis suggested the increased lipolysis in adipose tissue of OVX + iCR and OVX
+ E rats. Data from in vitro experiments using cultured primary rat adipocytes
also showed that black cohosh could affect lipolysis of adipocytes. In
conclusion, the long-term treatment of black cohosh at a proper dosage
ameliorated metabolic derangements in OVX rats. Thus, this drug is promising for
the treatment of metabolic disorders in menopausal and post-menopausal women.
PMID- 26414763
TI - Fellow As Teacher Curriculum: Improving Rheumatology Fellows' Teaching Skills
During Inpatient Consultation.
AB - OBJECTIVE: Enhancing rheumatology fellows' teaching skills in the setting of
inpatient consultation may have a broad positive impact. Such efforts may improve
fellows' clinical skills and overall patient care. Most importantly, effective
resident-fellow teaching interactions may not only increase residents' knowledge
of rheumatology but may influence their career choice. However, a number of
barriers to the resident-fellow teaching interaction have been identified,
including fellows' teaching skills. We developed the Fellow As Clinical Teacher
(FACT) curriculum in order to enhance fellows' teaching skills during inpatient
consultation. METHODS: The FACT curriculum was delivered in two 45-minute
workshops during the 3-day Winter Symposium of the Carolinas Fellows
Collaborative. We evaluated its effect with self-assessment surveys and fellow
performance on the objective structured teaching exercise (OSTE) before and after
participation in the curriculum. RESULTS: Nineteen fellows from 4 rheumatology
training programs participated in the pre- and post-curriculum OSTEs and 18
fellows completed pre- and post-curriculum surveys. OSTE scores improved on 5 of
the 8 items assessed, and the total OSTE score improved as well (34.7 versus
29.5; P < 0.01) after the FACT curriculum. Fellows' self-assessment of their
teaching skills and intent to teach during consultation also increased after
participation in the curriculum. CONCLUSION: The FACT curriculum, focused on
teaching during consultation, improved fellows' teaching skills and attitudes
toward teaching. Improving and increasing fellow teaching, particularly in the
consultation setting, may impact patient care, resident and fellow learning, and
teaching skills of future faculty, and could potentially influence residents'
career choice.
PMID- 26414764
TI - Glycolysis controls the induction of human regulatory T cells by modulating the
expression of FOXP3 exon 2 splicing variants.
AB - Human regulatory T cells (T(reg) cells) that develop from conventional T cells
(T(conv) cells) following suboptimal stimulation via the T cell antigen receptor
(TCR) (induced T(reg) cells (iT(reg) cells)) express the transcription factor
Foxp3, are suppressive, and display an active proliferative and metabolic state.
Here we found that the induction and suppressive function of iT(reg) cells
tightly depended on glycolysis, which controlled Foxp3 splicing variants
containing exon 2 (Foxp3-E2) through the glycolytic enzyme enolase-1. The Foxp3
E2-related suppressive activity of iT(reg) cells was altered in human autoimmune
diseases, including multiple sclerosis and type 1 diabetes, and was associated
with impaired glycolysis and signaling via interleukin 2. This link between
glycolysis and Foxp3-E2 variants via enolase-1 shows a previously unknown
mechanism for controlling the induction and function of T(reg) cells in health
and in autoimmunity.
PMID- 26414767
TI - Influence of Solid-State Packing of Dipolar Merocyanine Dyes on Transistor and
Solar Cell Performances.
AB - A series of nine dipolar merocyanine dyes has been studied as organic
semiconductors in transistors and solar cells. These dyes exhibited single
crystal packing motifs with different dimensional ordering, which can be
correlated to the performance of the studied devices. Hereby, the long-range
ordering of the dyes in staircase-like slipped stacks with J-type excitonic
coupling favors charge transport and improves solar cell performance. The
different morphologies of transistor thin films and solar cell active layers were
investigated by UV-vis, AFM, and XRD experiments. Selenium-containing donor
acceptor (D-A) dimethine dye 4 showed the highest hole mobility of 0.08 cm(2) V(
1) s(-1). BHJ solar cells based on dye 4 were optimized by taking advantage of
the high crystallinity of the donor material and afforded a PCE of up to 6.2%.
PMID- 26414765
TI - Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen
species and bactericidal activity.
AB - Mitochondria need to be juxtaposed to phagosomes for the synergistic production
of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However,
how phagosomes transmit signals to recruit mitochondria has remained unclear.
Here we found that the kinases Mst1 and Mst2 functioned to control ROS production
by regulating mitochondrial trafficking and mitochondrion-phagosome
juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like
receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for
the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including
the human Rac2(D57N) mutant, disrupted the TRAF6-ECSIT complex by sequestering
TRAF6 and substantially diminished ROS production and enhanced susceptibility to
bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac
signaling axis is critical for effective phagosome-mitochondrion function and
bactericidal activity.
PMID- 26414768
TI - The Neoadjuvant Paradigm for Development of Systemic Therapy and Precision
Medicine for Bladder Cancer.
PMID- 26414766
TI - Runx3 specifies lineage commitment of innate lymphoid cells.
AB - Subsets of innate lymphoid cells (ILCs) reside in the mucosa and regulate immune
responses to external pathogens. While ILCs can be phenotypically classified into
ILC1, ILC2 and ILC3 subsets, the transcriptional control of commitment to each
ILC lineage is incompletely understood. Here we report that the transcription
factor Runx3 was essential for the normal development of ILC1 and ILC3 cells but
not of ILC2 cells. Runx3 controlled the survival of ILC1 cells but not of ILC3
cells. Runx3 was required for expression of the transcription factor RORgammat
and its downstream target, the transcription factor AHR, in ILC3 cells. The
absence of Runx3 in ILCs exacerbated infection with Citrobacter rodentium.
Therefore, our data establish Runx3 as a key transcription factor in the lineage
specific differentiation of ILC1 and ILC3 cells.
PMID- 26414769
TI - Radiation Dosimetry for Ureteroscopy Patients: A Phantom Study Comparing the
Standard and Obese Patient Models.
AB - PURPOSE: To determine the effect of obesity on radiation exposure during
simulated ureteroscopy. METHODS: A validated anthropomorphic adult male phantom
with a body mass index (BMI) of approximately 24 kg/m(2), was positioned to
simulate ureteroscopy. Padding with radiographic characteristics of human fat was
placed around the phantom to create an obese model with BMI of 30 kg/m(2). Metal
oxide semiconductor field effect transistor (MOSFET) dosimeters were placed at 20
organ locations in both models to measure organ dosages. A portable C-arm was
used to provide fluoroscopic x-ray radiation to simulate ureteroscopy. Organ dose
rates were calculated by dividing organ dose by fluoroscopy time. Effective dose
rate (EDR, mSv/sec) was calculated as the sum of organ dose rates multiplied by
corresponding ICRP 103 tissue weighting factors. RESULTS: The mean EDR was
significantly increased during left ureteroscopy in the obese model at 0.0092 +/-
0.0004 mSv/sec compared with 0.0041 +/- 0.0003 mSv/sec in the nonobese model (P <
0.01), as well as during right ureteroscopy at 0.0061 +/- 0.0002 and 0.0036 +/-
0.0007 mSv/sec in the obese and nonobese model, respectively (P < 0.01). EDR
during left ureteroscopy was significantly greater than right ureteroscopy in the
obese model (P = 0.02). CONCLUSIONS: Fluoroscopy during ureteroscopy contributes
to the overall radiation dose for patients being treated for nephrolithiasis.
Obese patients are at even higher risk because of increased exposure rates during
fluoroscopy. Every effort should be made to minimize the amount of fluoroscopy
used during ureteroscopy, especially with obese patients.
PMID- 26414770
TI - Corrigendum to 'Herpesvirus of turkeys: Microarray analysis of host gene
responses to infection' [Virology 318 (2004) 102-111].
PMID- 26414771
TI - Corrigendum to "Increased expression of cytokines, soluble cytokine receptors,
soluble apoptosis ligand and apoptosis in dengue" [Virology 452-453 (2014) 42
51].
PMID- 26414772
TI - Application of the MERIT survey in the multi-criteria quality assessment of
occupational health and safety management.
AB - Occupational health and safety management systems apply audit examinations as an
integral element of these systems. The examinations are used to verify whether
the undertaken actions are in compliance with the accepted regulations, whether
they are implemented in a suitable way and whether they are effective. One of the
earliest solutions of that type applied in the mining industry in Poland involved
the application of audit research based on the MERIT survey (Management
Evaluation Regarding Itemized Tendencies). A mathematical model applied in the
survey facilitates the determination of assessment indexes WOPi for each of the
assessed problem areas, which, among other things, can be used to set up problem
area rankings and to determine an aggregate (synthetic) assessment. In the paper
presented here, the assessment indexes WOPi were used to calculate a development
measure, and the calculation process itself was supplemented with sensitivity
analysis.
PMID- 26414773
TI - Two new proanthocyanidin trimers isolated from Cistus incanus L. demonstrate
potent anti-inflammatory activity and selectivity to cyclooxygenase isoenzymes
inhibition.
AB - Two new proanthocyanidin trimers have been isolated from Cistus incanus herb;
gallocatechin-(4alpha->6)-gallocatechin-(4alpha->8)-gallocatechin (compound 1)
and epigallocatechin-3-O-gallate-(4beta->8)-epigallocatechin-3-O-gallate-(4beta
>8)-gallocatechin (compound 2). The structures were determined on the basis of 1D
and 2D-NMR (HSQC, HMBC) of their peracetylated derivatives, MALDI-TOF-MS and by
acid-catalysed degradation with phloroglucinol. A more abundant proanthocyanidin
oligomer was also isolated, purified and its chemical constitution studied by
(13)C-NMR and phloroglucinol degradation. The mean molecular weight of the
polymer was estimated to be about 7 to 8 flavan-3-ol-units with a ratio of
procyanidin : prodelphinidin units at 1:5, some of which are derivatised by
gallic acid. Water extract and higher oligomeric proanthocyanidin fractions of C.
incanus significantly inhibited TPA-induced oedema when applied topically at
doses of 0.5 and 1 mg/ear in mice. Furthermore, the extracts and the pure
compounds inhibited COX-1 and COX-2 activities. In addition, compound 2 exhibited
an IC50 of 4.5 MUM against COX-2 indicating its high selectivity towards COX-2.
PMID- 26414775
TI - Poverty, Depression, or Lost in Translation? Ethnic and Language Variation in
Patient-Reported Outcomes in Rheumatoid Arthritis.
AB - OBJECTIVE: Despite advances in therapies, disparities in outcomes have been
documented for rheumatoid arthritis (RA) patients for both ethnicity and English
language proficiency. The goals of these analyses were to compare differences in
RA patient-reported outcomes, by both self-identification of ethnicity and
English language proficiency, and to identify factors that might explain
differences among groups. METHODS: Data were collected through structured
telephone interviews of a longitudinal cohort with physician-diagnosed RA (n =
438); only women were included (n = 335). Three groups were defined based on self
reported ethnicity and English proficiency: white/English (n = 219),
Hispanic/English (n = 39), and Hispanic/Spanish (n = 77). Outcomes examined were
patient-reported physical functioning, pain, and presence of moderate or severe
fatigue. Multivariate regression analyses compared outcomes among groups,
adjusting for sociodemographic characteristics, health and disease factors, and
depression. RESULTS: Hispanic/Spanish women had worse function, pain, and fatigue
than either English-proficient group. Depression was associated with all outcomes
(P < 0.0001), and accounted for greater differentials in scores than
ethnicity/language proficiency. In interaction analyses, differences between
women who were and were not depressed were greater for Hispanic/English than for
Hispanic/Spanish. Nondepressed Hispanic/Spanish scores were significantly worse
than nondepressed Hispanic/English, i.e., the impact of depression was less for
Hispanic/Spanish women because both depressed and nondepressed women in this
group reported worse outcomes. After adjustment for sociodemographic factors and
depression, language remained significantly associated with outcomes. CONCLUSION:
Disparities in patient-reported outcomes may be driven less by ethnicity than by
sociodemographic or psychological factors. Measurement instruments that are not
culturally appropriate and equivalent may also hamper meaningful analyses of
disparities.
PMID- 26414774
TI - The selectivity of responses to red-green colour and achromatic contrast in the
human visual cortex: an fMRI adaptation study.
AB - There is controversy as to how responses to colour in the human brain are
organized within the visual pathways. A key issue is whether there are modular
pathways that respond selectively to colour or whether there are common neural
substrates for both colour and achromatic (Ach) contrast. We used functional
magnetic resonance imaging (fMRI) adaptation to investigate the responses of
early and extrastriate visual areas to colour and Ach contrast. High-contrast red
green (RG) and Ach sinewave rings (0.5 cycles/degree, 2 Hz) were used as both
adapting stimuli and test stimuli in a block design. We found robust adaptation
to RG or Ach contrast in all visual areas. Cross-adaptation between RG and Ach
contrast occurred in all areas indicating the presence of integrated, colour and
Ach responses. Notably, we revealed contrasting trends for the two test stimuli.
For the RG test, unselective processing (robust adaptation to both RG and Ach
contrast) was most evident in the early visual areas (V1 and V2), but selective
responses, revealed as greater adaptation between the same stimuli than cross
adaptation between different stimuli, emerged in the ventral cortex, in V4 and VO
in particular. For the Ach test, unselective responses were again most evident in
early visual areas but Ach selectivity emerged in the dorsal cortex (V3a and
hMT+). Our findings support a strong presence of integrated mechanisms for colour
and Ach contrast across the visual hierarchy, with a progression towards
selective processing in extrastriate visual areas.
PMID- 26414778
TI - Modelling of oxygen vacancy aggregates in monoclinic HfO2: can they contribute to
conductive filament formation?
AB - Formation of metal rich conductive filaments and their rearrangements determine
the switching characteristics in HfO2 based resistive random access memory (RRAM)
devices. The initiation of a filament formation process may occur either via
aggregation of pre-existing vacancies randomly distributed in the oxide or via
generation of new oxygen vacancies close to the pre-existing ones. We evaluate
the feasibility of vacancy aggregation processes by calculating the structures
and binding energies of oxygen vacancy aggregates consisting of 2, 3 and 4
vacancies in bulk monoclinic (m)-HfO2 using density functional theory (DFT). We
demonstrate that formation of neutral oxygen vacancy aggregates is accompanied by
small energy gain, which depends on the size and shape of the aggregate. In the
most strongly bound configurations, vacancies are unscreened by Hf cations and
form voids within the crystal, with the larger aggregates having larger binding
energy per vacancy (-0.11 to -0.18 eV). The negatively charged di-vacancy was
found to have similar binding energies to the neutral one, while the positively
charged di-vacancy was found to be unstable. Thus aggregation process of either
neutral or negatively charged oxygen vacancies is energetically feasible.
PMID- 26414776
TI - Pulse pressure amplification and its determinants.
AB - BACKGROUND: Pulse pressure (PP) amplification expressed as the peripheral-to
central PP ratio has gained importance in the assessment of cardiovascular
phenotypes and cardiovascular risk. The aim of the present study was to assess
the relationship between PP amplification, large vessel parameters and peripheral
blood pressure (BP) to gain insights into the amplification phenomenon. METHODS:
Peripheral BP, central BP and carotid-femoral pulse wave velocity (cfPWV) were
assessed using the OMRON M6, SphygmoCor and Complior devices, respectively, in
741 adults attending the hypertension outpatient clinic. Analysis of covariance,
partial correlations and multiple linear regression models were performed to
assess the relationship between PP amplification, peripheral BP and cfPWV.
RESULTS: PP amplification was inversely related to BP group. Women showed lower
PP amplification than men (1.24 +/- 0.18 and 1.35 +/- 0.18, respectively, p <
0.001). Age, female gender and mean arterial pressure were inversely associated
with PP amplification (p < 0.001), whereas heart rate and body mass index showed
positive associations (p < 0.001 and p = 0.049, respectively). cfPWV was a
predictor of PP amplification in men but not in women (p = 0.006 and p = 0.424,
respectively). CONCLUSIONS: PP amplification is related to BP: the higher the BP,
the lower the PP amplification. Gender, age and body composition have a
significant impact on PP amplification.
PMID- 26414777
TI - Human and Murine Tissue-Engineered Colon Exhibit Diverse Neuronal Subtypes and
Can Be Populated by Enteric Nervous System Progenitor Cells When Donor Colon Is
Aganglionic.
AB - PURPOSE: Tissue-engineered colon (TEC) might potentially replace absent or
injured large intestine, but the enteric nervous system (ENS), a key component,
has not been investigated. In various enteric neuropathic diseases in which the
TEC is derived from aganglionic donor colon, the resulting construct might also
be aganglionic, limiting tissue engineering applications in conditions such as
Hirschsprung disease (HD). We hypothesized that TEC might contain a diverse
population of enteric neuronal subtypes, and that aganglionic TEC can be
populated by neurons and glia when supplemented with ENS progenitor cells in the
form of neurospheres. MATERIALS AND METHODS: Human and murine organoid units (OU)
and multicellular clusters containing epithelium and mesenchyme were isolated
from both mouse and human donor tissues, including from normally innervated and
aganglionic colon. The OU were seeded onto a biodegradable scaffold and implanted
within a host mouse, resulting in the growth of TEC. Aganglionic murine and human
OU were supplemented with cultured neurospheres to populate the absent ENS not
provided by the OU to rescue the HD phenotype. RESULTS: TEC demonstrated abundant
smooth muscle and clusters of neurons and glia beneath the epithelium and deeper
within the mesenchyme. Motor and afferent neuronal subtypes were identified in
TEC. Aganglionic OU formed TEC with absent neural elements, but neurons and glia
were abundant when aganglionic OU were supplemented with ENS progenitor cells.
CONCLUSION: Murine and human TEC contain key components of the ENS that were not
previously identified, including glia, neurons, and fundamental neuronal
subtypes. TEC derived from aganglionic colon can be populated with neurons and
glia when supplemented with neurospheres. Combining tissue engineering and
cellular replacement therapies represents a new strategy for treating enteric
neuropathies, particularly HD.
PMID- 26414779
TI - Tuning the Tunneling Rate and Dielectric Response of SAM-Based Junctions via a
Single Polarizable Atom.
AB - The dielectric response and electrical properties of junctions based on self
assembled monolayers (SAMs) of the form S(CH2)11X can be controlled by changing
the polarizability of X (here X = H, F, Cl, Br, or I). A 1000-fold increase in
the tunneling rate and a four-fold increase of the dielectric constant (epsilon r
) with increasing polarizability of X are found.
PMID- 26414780
TI - Reassessment of MTBE cancer potency considering modes of action for MTBE and its
metabolites.
AB - A 1999 California state agency cancer potency (CP) evaluation of methyl tert
butyl ether (MTBE) assumed linear risk extrapolations from tumor data were
plausible because of limited evidence that MTBE or its metabolites could damage
DNA, and based such extrapolations on data from rat gavage and rat and mouse
inhalation studies indicating elevated tumor rates in male rat kidney, male rat
Leydig interstitial cells, and female rat leukemia/lymphomas. More recent data
bearing on MTBE cancer potency include a rodent cancer bioassay of MTBE in
drinking water; several new studies of MTBE genotoxicity; several similar
evaluations of MTBE metabolites, formaldehyde, and tert-butyl alcohol or TBA; and
updated evaluations of carcinogenic mode(s) of action (MOAs) of MTBE and MTBE
metabolite's. The lymphoma/leukemia data used in the California assessment were
recently declared unreliable by the U.S. Environmental Protection Agency (EPA).
Updated characterizations of MTBE CP, and its uncertainty, are currently needed
to address a variety of decision goals concerning historical and current MTBE
contamination. To this end, an extensive review of data sets bearing on MTBE and
metabolite genotoxicity, cytotoxicity, and tumorigenicity was applied to reassess
MTBE CP and related uncertainty in view of MOA considerations. Adopting the
traditional approach that cytotoxicity-driven cancer MOAs are inoperative at very
low, non-cytotoxic dose levels, it was determined that MTBE most likely does not
increase cancer risk unless chronic exposures induce target-tissue toxicity,
including in sensitive individuals. However, the corresponding expected (or
plausible upper bound) CP for MTBE conditional on a hypothetical linear (e.g.,
genotoxic) MOA was estimated to be ~2 * 10(-5) (or 0.003) per mg MTBE per kg body
weight per day for adults exposed chronically over a lifetime. Based on this
conservative estimate of CP, if MTBE is carcinogenic to humans, it is among the
weakest 10% of chemical carcinogens evaluated by EPA.
PMID- 26414781
TI - Monotherapy for hepatitis B infection: a review of treatment options.
AB - Chronic hepatitis B (CHB) is a global health problem, causing liver failure,
cirrhosis and hepatocellular carcinoma. CHB treatment aims to prevent liver
related complication. The treatment of CHB infection includes monotherapy with
either interferons (IFNs) or nucleos(t)ide (NUC) analogs. IFNs have moderate
antiviral effects, and their use is limited by side effects. With the
availability of NUCs, IFN-intolerant and decompensated cirrhotic patients began
to be treated. Lamivudine and telbivudine, nucleoside analogs, have low genetic
barrier to resistance. Adefovir, a nucleotide analog, has moderate potency and
potential nephrotoxicity. Entecavir and tenofovir, with their high potency, high
genetic barrier to resistance and favorable safety profile are the standard of
care in CHB treatment. Long-term use of NUCs with maintained viral suppression
results in a decrease in liver-related complications.
PMID- 26414782
TI - Differential osteogenic potential of human adipose-derived stem cells co-cultured
with human osteoblasts on polymeric microfiber scaffolds.
AB - The osteogenic potential of human adipose-derived stem cells (HADSCs) co-cultured
with human osteoblasts (HOBs) using selected HADSCs/HOBs ratios of 1:1, 2:1, and
1:2, respectively, is evaluated. The HADSCs/HOBs were seeded on electrospun three
dimensional poly[(R)-3-hydroxybutyric acid] (PHB) blended with bovine-derived
hydroxyapatite (BHA). Monocultures of HADSCs and HOBs were used as control
groups. The effects of PHB-BHA scaffold on cell proliferation and cell morphology
were assessed by AlamarBlue assay and field emission scanning electron
microscopy. Cell differentiation, cell mineralization, and osteogenic-related
gene expression of co-culture HADSCs/HOBs were examined by alkaline phosphatase
(ALP) assay, alizarin Red S assay, and quantitative real time PCR, respectively.
The results showed that co-culture of HADSCs/HOBs, 1:1 grown into PHB-BHA
promoted better cell adhesion, displayed a significant higher cell proliferation,
higher production of ALP, extracellular mineralization and osteogenic-related
gene expression of run-related transcription factor, bone sialoprotein,
osteopontin, and osteocalcin compared to other co-culture groups. This result
also suggests that the use of electrospun PHB-BHA in a co-culture HADSCs/HOBs
system may serve as promising approach to facilitate osteogenic differentiation
activity of HADSCs through direct cell-to-cell contact with HOBs.
PMID- 26414783
TI - The clubfoot painted by Jusepe de Ribera: a controversial diagnosis.
AB - The Clubfoot painted by Jose de Ribera depicts a young beggar affected by a
typical equinus clubfoot. He shows a contorted right hand and wrist. His left
hand holds a begging note, suggesting some difficulty to speak. This condition
may be caused by a cerebral palsy, consisting of a brain injury in the left
hemisphere responsible for right hemiplegia and speech disturbance. Recently, it
was suggested that the boy's condition is a consequence of arthrogryposis,
perhaps amyoplasia or distal arthrogryposis type A1. Some clinical features may
suggest the diagnosis of Sheldon-Hall syndrome. Considering all the signs
represented on the painting, the diagnosis of hemiplegia due to cerebral palsy
cannot be discarded. The present article is a novel analysis of the painting
based on previously proposed diagnoses of the boy's condition, namely, hemiplegia
and arthrogryposis.
PMID- 26414784
TI - Therapies in early development for the treatment of opiate addiction.
AB - INTRODUCTION: Opiate drugs are psychoactive substances used to manage severe
pain. However, their chronic use is associated with the development of addiction.
Opiate addiction represents a significant public health concern. AREAS COVERED:
This review focuses on the most recent advances in the pharmacological treatment
of opiate addiction, from those being tested in clinical trials (Phase I and II),
to preclinical studies that point to new targets. Readers will gain knowledge of
the wide variety of treatments used to treat opiate addiction, including their
strengths and weaknesses, and the promising pharmacological targets identified by
preclinical research. EXPERT OPINION: Among the currently available agonist
therapies, new dosage forms of buprenorphine can increase patient acceptability
and compliance. New extended-release forms of naltrexone are building hope of
retaining opiate-dependent subjects in a drug-free state. Unfortunately, the
review of the literature shows that successful preclinical studies are often
followed by discouraging results in human clinical trials. Nevertheless, all
targets of potential interest should be tested exhaustively. Indeed, a number of
new targets and research lines (genetics and neuroinflammation approaches) may
lead to breakthroughs in the future.
PMID- 26414785
TI - The Effect of Swelling Ratio on the Coulter Underestimation of Hydrogel
Microsphere Diameters.
AB - It has been demonstrated that the diameters of porous particles are
underestimated by Coulter measurements. This phenomenon has also been observed in
hydrogel particles, but not characterized. Since the Coulter principle uses the
displacement of electrolyte to determine particle size, electrolyte contained
within the swelled hydrogel microparticles results in an underestimate of actual
particle diameters. The increased use of hydrogel microspheres in biomedical
applications has led to the increased application of the Coulter principle to
evaluate the size distribution of microparticles. A relationship between the
swelling ratio of the particles and their reported Coulter diameters will permit
calculation of the actual diameters of these particles. Using polyethylene glycol
diacrylate hydrogel microspheres, we determined a correction factor that relates
the polymer swelling ratio and the reported Coulter diameters to their actual
size.
PMID- 26414786
TI - From Annoying to Appreciated: Turning clinical decision support systems into a
medical professional's best friend.
AB - There's a big difference between driving suggestions that come from a newly
licensed, know-it-all teenager and those that come from a professional racecar
driver who has spent years honing skills on the course. The first is one you just
want to be quiet, and the second is one you actually want to speak up.
PMID- 26414787
TI - Breathing Easier: Model-based decision support for respiratory care looks beyond
tomorrow.
AB - Mechanical ventilation (MV) is a primary therapy for intensive care unit (ICU)
patients who have respiratory failure. Up to ~60% of all ICU patients require MV,
and?because they are so ill?this patient group stays in the ICU 50?100% longer.
They also cost almost 100% more due to this added care, and, troublingly, have a
mortality rate of almost 30%.
PMID- 26414788
TI - Throw Science to the Dogs: The best models for human disease may just be right
under scientists' noses--if not in their laps.
AB - Opportunities for gathering vital information on cancer, heart disease, and other
complicated diseases via clinical models are missed despite the at least 70
million pet dogs and 74 million pet cats in the United States alone that
experience these very illnesses. This article presents a general discussion on
the current state and hindrances to comparative medicine.
PMID- 26414789
TI - Mind Your Composition: Clinical validation of Samsung's pocket-based
bioelectrical impedance analyzers may increase consumer interest in personal
health management.
AB - When asked about our weight, most of us can name a figure based on prior
knowledge. And while stepping on a scale gives us the ability to know that exact
number and track it routinely, it does not provide insights into our body?s
composition. This, at the basic level, refers to proportions of fat and lean or
fat-free mass (FFM) that comprise the human body. Conventionally, the body mass
index (BMI), which is the ratio of body weight in kilograms to the square of its
height in meters, and anthropometric parameters like waist circumference, waist
to-hip ratio, and skinfold thickness have been used to estimate the level of
fatness. In fact, BMI is the de facto marker for stratifying individuals into
underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2),
and obese (>30 kg/m2) categories. Nonetheless, these metrics are limited in
precisely characterizing individuals by percentages of body fat and muscle mass,
particularly in epidemiological studies where these proportions vary across age,
sex, and ethnic groups. Of note is also how, solely on the basis of BMI, a
physically fit individual may be classified as overweight due to having a higher
proportion of lean body mass, which outweighs fat. This highlights the importance
of body composition in weight tracking and management.
PMID- 26414790
TI - Next-Gen Gene Synthesis Enables Large-Scale Engineering in Biological Systems:
Recent advances in synthetic biology are making this field more promising than
ever.
AB - As scientists make strides toward the goal of developing a form of biological
engineering that's as predictive and reliable as chemical engineering is for
chemistry, one technology component has become absolutely critical: gene
synthesis. Gene synthesis is the process of building stretches of
deoxyribonucleic acid (DNA) to order--some stretches based on DNA that exists
already in nature, some based on novel designs intended to accomplish new
functions. This process is the foundation of synthetic biology, which is rapidly
becoming the engineering counterpart to biology.
PMID- 26414791
TI - Rethinking Education: When surgeons and engineering students join forces to solve
real problems, success follows.
AB - The Engineers in Scrubs (EiS) training program at the University of British
Columbia, affiliated with the Faculty of Applied Science?s Biomedical Engineering
Graduate (BMEG) Program, is not a typical graduate school course. Nor does it
follow a traditional master?s course rubric that culminates with a tidy end-of
year project. Rather, the course is designed to push students to prototype
innovative medical devices, encourage health care collaborations, and create an
unprecedented interface between technology and health care to further medicine.
PMID- 26414792
TI - New Imaging Technology May Help Doctors Diagnose Amyloidosis: Due to stringent
FDA rules, U.S. imaging of the disease has lagged behind Europe but a new
synthetic molecule may change that.
AB - One December day in 2013, Michael Rasmussen realized that just chewing his food
made him tired. Short walks felt draining. At one point, he became so tired that
he sat down and didn't get up for three days. Rasmussen had been a man in perfect
health. For 30 years, he lived as an artist in the Aleutian Islands in Alaska and
walked or biked everywhere. He even bicycled across the United States five times.
But now he had slid into a horrible medical mystery.
PMID- 26414793
TI - Reconstructing Large-Scale Brain Resting-State Networks from High-Resolution EEG:
Spatial and Temporal Comparisons with fMRI.
AB - Functional magnetic resonance imaging (fMRI) studies utilizing measures of
hemodynamic signal, such as the blood oxygenation level-dependent (BOLD) signal,
have discovered that resting-state brain activities are organized into multiple
large-scale functional networks, coined as resting-state networks (RSNs).
However, an important limitation of the available fMRI studies is that
hemodynamic signals only provide an indirect measure of the neuronal activity. In
contrast, electroencephalography (EEG) directly measures electrophysiological
activity of the brain. However, little is known about the brain-wide organization
of such spontaneous neuronal population signals at the resting state. It is not
entirely clear if or how the network structure built upon slowly fluctuating
hemodynamic signals is represented in terms of fast, dynamic, and spontaneous
neuronal activity. In this study, we investigated the electrophysiological
representation of RSNs from simultaneously acquired EEG and fMRI data in the
resting human brain. We developed a data-driven analysis approach that
reconstructed multiple large-scale electrophysiological networks from high
resolution EEG data alone. The networks derived from EEG were then compared with
RSNs independently derived from simultaneously acquired fMRI in their spatial
structures as well as temporal dynamics. Results reveal spatially and temporally
specific electrophysiological correlates for the fMRI-RSNs. Findings suggest that
the spontaneous activity of various large-scale cortical networks is reflected in
macroscopic EEG potentials.
PMID- 26414794
TI - CXCL12/CXCR4 activation by cancer-associated fibroblasts promotes integrin beta1
clustering and invasiveness in gastric cancer.
AB - Cancer-associated fibroblasts (CAFs) are reportedly involved in invasion and
metastasis in several types of cancer, including gastric cancer (GC), through the
stimulation of CXCL12/CXCR4 signaling. However, the mechanisms underlying these
tumor-promoting effects are not well understood, which limits the potential to
develop therapeutic targets against CAF-mediated CXCL12/CXCR4 signaling. CXCL12
expression was analyzed in resected GC tissues from 110 patients by
immunohistochemistry (IHC). We established primary cultures of normal fibroblasts
(NFs) and CAFs from the GC tissues and examined the functional differences
between these primary fibroblasts using co-culture assays with GC cell lines. We
evaluated the efficacy of a CXCR4 antagonist (AMD3100) and a FAK inhibitor (PF
573,228) on the invasive ability of GC cells. High CXCL12 expression levels were
significantly associated with larger tumor size, increased tumor depth, lymphatic
invasion and poor prognosis in GC. CXCL12/CXCR4 activation by CAFs mediated
integrin beta1 clustering at the cell surface and promoted the invasive ability
of GC cells. Notably, AMD3100 was more efficient than PF-573,228 at inhibiting GC
cell invasion through the suppression of integrin beta1/FAK signaling. These
results suggest that CXCL12 derived from CAFs promotes GC cell invasion by
enhancing the clustering of integrin beta1 in GC cells, resulting in GC
progression. Taken together, the inhibition of CXCL12/CXCR4 signaling in GC cells
may be a promising therapeutic strategy against GC cell invasion.
PMID- 26414795
TI - Bone Marrow Stromal Cell Intraspinal Transplants Fail to Improve Motor Outcomes
in a Severe Model of Spinal Cord Injury.
AB - Bone marrow stromal cells (BMSCs) have been reported to exert potential
neuroprotective properties in models of neurotrauma, although precise mechanisms
underlying their benefits are poorly understood. Despite this lack of knowledge,
several clinical trials have been initiated using these cells. To determine
whether local mechanisms mediate BMSC neuroprotective actions, we grafted
allogeneic BMSCs to sites of severe, compressive spinal cord injury (SCI) in
Sprague-Dawley rats. Cells were administered 48 h after the original injury.
Additional animals received allogeneic MSCs that were genetically modified to
secrete brain-derived neurotrophic factor (BDNF) to further determine whether a
locally administered neurotrophic factor provides or extends neuroprotection.
When assessed 2 months post-injury in a clinically relevant model of severe SCI,
BMSC grafts with or without BDNF secretion failed to improve motor outcomes.
Thus, allogeneic grafts of BMSCs do not appear to act through local mechanisms,
and future clinical trials that acutely deliver BMSCs to actual sites of injury
within days are unlikely to be beneficial. Additional studies should address
whether systemic administration of BMSCs alter outcomes from neurotrauma.
PMID- 26414796
TI - Suppression of atopic dermatitis in mice model by reducing inflammation utilizing
phosphatidylserine-coated biodegradable microparticles.
AB - Controlling inflammatory response is important to avoid chronic inflammation in
many diseases including atopic dermatitis (AD). In this research, we tried using
a phosphatidylserine (PS)-coated microparticles in the AD mouse model for
achieving the modulation of the macrophage phenotype to an anti-inflammatory
state. Here, we prepared poly (D,L-lactic acid) microparticle coated with PS on
the outside shell. We confirmed the cellular uptake of the PS-coated
microparticle, which leads to the significant downregulation of the inflammatory
cytokine production. In the mouse model of AD, the PS-coated microparticle was
injected subcutaneously for a period of 12 days. The mice showed significant
reduction in the development of AD symptoms comparing with the mice treated with
the PC-coated microparticle.
PMID- 26414797
TI - SMAD Signaling in the Airways of Healthy Rhesus Macaques versus Rhesus Macaques
with Asthma Highlights a Relationship Between Inflammation and Bone Morphogenetic
Proteins.
AB - Bone morphogenetic protein (BMP) signaling is important for correct lung
morphogenesis, and there is evidence of BMP signaling reactivation in lung
diseases. However, little is known about BMP signaling patterns in healthy airway
homeostasis and inflammatory airway disease and during epithelial repair. In this
study, a rhesus macaque (Macaca mulatta) model of allergic airway disease was
used to investigate BMP signaling throughout the airways in health, disease, and
regeneration. Stereologic quantification of immunofluorescent images was used to
determine the expression of BMP receptor (BMPR) Ia and phosphorylated SMAD
(pSMAD) 1/5/8 in the airway epithelium. A pSMAD 1/5/8 expression gradient was
found along the airways of healthy juvenile rhesus macaques (n = 3, P < 0.005).
Membrane-localized BMPRIa expression was also present in the epithelium of the
healthy animals. After exposure to house dust mite allergen and ozone,
significant down-regulation of nuclear pSMAD 1/5/8 occurs in the epithelium. When
the animals were provided with a recovery period in filtered air, proliferating
cell nuclear antigen, pSMAD 1/5/8, and membrane-localized BMPRIa expression were
significantly increased in the epithelium of conducting airways (P < 0.005).
Furthermore, in the asthmatic airways, altered BMPRIa localization was evident.
Because of the elevated eosinophil presence in these airways, we investigated the
effect of eosinophil-derived proteins on BMPRIa trafficking in epithelial cells.
Eosinophil-derived proteins (eosinophil-derived neurotoxin, eosinophil
peroxidase, and major basic protein) induced transient nuclear translocation of
membrane-bound BMPRIa. This work mapping SMAD signaling in the airways of
nonhuman primates highlights a potential mechanistic relationship between
inflammatory mediators and BMP signaling and provides evidence that basal
expression of the BMP signaling pathway may be important for maintaining healthy
airways.
PMID- 26414798
TI - A situational analysis methodology to inform comprehensive HIV prevention and
treatment programming, applied in rural South Africa.
AB - Successful HIV prevention programming requires engaging communities in the
planning process and responding to the social environmental factors that shape
health and behaviour in a specific local context. We conducted two community
based situational analyses to inform a large, comprehensive HIV prevention
programme in two rural districts of North West Province South Africa in 2012. The
methodology includes: initial partnership building, goal setting and background
research; 1 week of field work; in-field and subsequent data analysis; and
community dissemination and programmatic incorporation of results. We describe
the methodology and a case study of the approach in rural South Africa; assess if
the methodology generated data with sufficient saturation, breadth and utility
for programming purposes; and evaluate if this process successfully engaged the
community. Between the two sites, 87 men and 105 women consented to in-depth
interviews; 17 focus groups were conducted; and 13 health facilities and 7 NGOs
were assessed. The methodology succeeded in quickly collecting high-quality data
relevant to tailoring a comprehensive HIV programme and created a strong
foundation for community engagement and integration with local health services.
This methodology can be an accessible tool in guiding community engagement and
tailoring future combination HIV prevention and care programmes.
PMID- 26414799
TI - Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic
Regulatory T Cells.
AB - Regulatory T cell (Treg)-based therapy is a promising approach to treat many
immune-mediated disorders such as autoimmune diseases, organ transplant
rejection, and graft-versus-host disease (GVHD). Challenges to successful
clinical implementation of adoptive Treg therapy include difficulties isolating
homogeneous cell populations and developing expansion protocols that result in
adequate numbers of cells that remain stable, even under inflammatory conditions.
We investigated the potential of discarded human thymuses, routinely removed
during pediatric cardiac surgery, to be used as a novel source of therapeutic
Tregs. Here, we show that large numbers of FOXP3(+) Tregs can be isolated and
expanded from a single thymus. Expanded thymic Tregs had stable FOXP3 expression
and long telomeres, and suppressed proliferation and cytokine production of
activated allogeneic T cells in vitro. Moreover, expanded thymic Tregs delayed
development of xenogeneic GVHD in vivo more effectively than expanded Tregs
isolated based on CD25 expression from peripheral blood. Importantly, in contrast
to expanded blood Tregs, expanded thymic Tregs remained stable under inflammatory
conditions. Our results demonstrate that discarded pediatric thymuses are an
excellent source of therapeutic Tregs, having the potential to overcome
limitations currently hindering the use of Tregs derived from peripheral or cord
blood.
PMID- 26414800
TI - Integrating plant carbon dynamics with mutualism ecology.
AB - Plants reward microbial and animal mutualists with carbohydrates to obtain
nutrients, defense, pollination, and dispersal. Under a fixed carbon budget,
plants must allocate carbon to their mutualists at the expense of allocation to
growth, reproduction, or storage. Such carbon trade-offs are indirectly expressed
when a plant exhibits reduced growth or fecundity in the presence of its
mutualist. Because carbon regulates the costs of all plant mutualisms, carbon
dynamics are a common platform for integrating these costs in the face of
ecological complexity and context dependence. The ecophysiology of whole-plant
carbon allocation could thus elucidate the ecology and evolution of plant
mutualisms. If mutualisms are costly to plants, then they must be important but
frequently underestimated sinks in the terrestrial carbon cycle.
PMID- 26414801
TI - Genetics of coronary artery disease: Short people at risk?
AB - Traditional cardiovascular risk factors have been in the spotlight for coronary
artery disease (CAD) management over the past decades. A non-modifiable risk
marker is short adult stature. However, a causal role in the etiology of CAD was
always questioned, since multiple confounders may also explain the inverse
association between height and CAD risk. The assumption that genetic variants
affecting height do so without interference of exogenous factors allows for the
testing of the association between short stature, that is, genetic markers
affecting height, and CAD even without measuring height. Interestingly, these
studies suggest a rather multifaceted relationship between the two complex
phenotypes. Indeed, investigating 180 height-associated genetic variants in
65,066 patients with CAD and 128,383 healthy controls suggests a causal
relationship of short stature and CAD risk. Multiple signaling pathways affecting
growth, as well as pleiotropic effects of genetic variants affecting height and
lipids, seem to underlie the association between height and CAD risk.
PMID- 26414803
TI - Multidimensional Neuropathic Pain Phenotypes after Spinal Cord Injury.
AB - Identifying clinical neuropathic pain phenotypes is a first step to better
understand the underlying pain mechanisms after spinal cord injury (SCI). The
primary purpose of the present study was to characterize multidimensional
neuropathic pain phenotypes based on quantitative sensory testing (QST), pain
intensity, and utilization of catastrophizing coping strategies. Thermal
perception, thermal pain, and vibratory perception thresholds were assessed above
and below the level of injury (LOI) in 101 persons with SCI and neuropathic pain,
18 persons with SCI and no neuropathic pain, and 50 able-bodied, pain-free
controls. Cluster analysis of QST z-scores below the LOI, pain intensity ratings,
and the Coping Strategies Questionnaire (CSQ) catastrophizing subscale scores in
subjects with neuropathic pain resulted in two phenotypes: severe neuropathic
pain (SNP) with greater pain intensity (7.39 +/- 1.57) and thermal and vibratory
sensitivity compared with the moderate neuropathic pain (MNP; 5.40 +/- 1.43). A
factor analysis including all CSQ subscales, the Neuropathic Pain Symptom
Inventory (NPSI) total score, and thermal pain sensitivity above and below the
LOI resulted in three factors: (1) adaptive pain coping including increasing
activities, diverting attention, and reinterpreting pain sensations; (2)
catastrophizing, neuropathic pain, and thermal sensitivity including greater NPSI
total score, thermal pain sensitivity below the LOI, and catastrophizing; and (3)
general pain sensitivity including greater thermal pain sensitivity above the LOI
and lower catastrophizing. Our results suggest that neuropathic pain symptom
severity post-SCI is significantly associated with residual spinothalamic tract
function below the LOI and catastrophizing pain coping.
PMID- 26414802
TI - Experience With the Priority Review Voucher Program for Drug Development.
PMID- 26414804
TI - Cysteine Mutational Studies Provide Insight into a Thiol-Based Redox Switch
Mechanism of Metal and DNA Binding in FurA from Anabaena sp. PCC 7120.
AB - AIMS: The ferric uptake regulator (Fur) is the main transcriptional regulator of
genes involved in iron homeostasis in most prokaryotes. FurA from Anabaena sp.
PCC 7120 contains five cysteine residues, four of them arranged in two redox
active CXXC motifs. The protein needs not only metal but also reducing conditions
to remain fully active in vitro. Through a mutational study of the cysteine
residues present in FurA, we have investigated their involvement in metal and DNA
binding. RESULTS: Residue C101 that belongs to a conserved CXXC motif plays an
essential role in both metal and DNA binding activities in vitro. Substitution of
C101 by serine impairs DNA and metal binding abilities of FurA. Isothermal
titration calorimetry measurements show that the redox state of C101 is
responsible for the protein ability to coordinate the metal corepressor.
Moreover, the redox state of C101 varies with the presence or absence of C104 or
C133, suggesting that the environments of these cysteines are mutually
interdependent. INNOVATION: We propose that C101 is part of a thiol/disulfide
redox switch that determines FurA ability to bind the metal corepressor.
CONCLUSION: This mechanism supports a novel feature of a Fur protein that emerges
as a regulator, which connects the response to changes in the intracellular redox
state and iron management in cyanobacteria. Antioxid. Redox Signal. 00, 000-000.
PMID- 26414805
TI - Resolution of Skin Fibrosis by Neutralization of the Antifibrinolytic Function of
Plasminogen Activator Inhibitor 1.
AB - OBJECTIVE: Systemic sclerosis (SSc) is a fibrotic disease characterized by an
obliterative vasculopathy with thrombosis and impairment of the coagulation
fibrinolysis balance. Plasminogen activator inhibitor 1 (PAI-1) is the major
inhibitor of profibrinolytic plasminogen activators (PAs). This study was
undertaken to evaluate the contribution of PAI-1 to SSc pathology in the skin.
METHODS: PAI-1 was evaluated in skin from patients with diffuse SSc (dSSc) and
those with limited SSc (lSSc) by immunohistochemistry. The contribution of PAI-1
to SSc pathology was tested in vivo in murine graft-versus-host disease (GVHD)
and bleomycin models of progressive skin fibrosis and in vitro in dermal human
microvascular endothelial cells (HMVECs) using a monoclonal antibody that
selectively prevents the binding of PAI-1 to PA. RESULTS: Skin from patients with
dSSc and those with lSSc showed increased PAI-1 levels in the epidermis and
microvessel endothelium. PAI-1 neutralization in the GVHD model led to a
dramatic, dose-dependent improvement in clinical skin score, concomitant with
vasculopathy resolution, including a reduction in fibrinolysis regulators and
vascular injury markers, as well as reduced inflammation. Resolution of
vasculopathy and inflammation was associated with resolution of skin fibrosis, as
assessed by reduction in collagen content and expression of key profibrotic
mediators, including transforming growth factor beta1 and tissue inhibitor of
metalloproteinases 1. Similar to the GVHD model, PAI-1 neutralization reduced
dermal inflammation and fibrosis in the bleomycin model. PAI-1 neutralization
stimulated plasmin-mediated metalloproteinase 1 activation in dermal HMVECs.
CONCLUSION: Our findings indicate that neutralization of the antifibrinolytic
function of PAI-1 resolves skin fibrosis by limiting the extent of initial
vascular injury and connective tissue inflammation. These data suggest that PAI-1
represents an important checkpoint in disease pathology in human SSc.
PMID- 26414806
TI - Growth-Arrest-Specific 7 Gene Regulates Neural Crest Formation and Craniofacial
Development in Zebrafish.
AB - Growth-arrest-specific 7 (Gas7) is preferentially expressed in the nervous system
and plays an important role during neuritogenesis in vertebrates. We recently
demonstrated that gas7 is highly expressed in zebrafish neurons, where it
regulates neural development. The possibility that gas7 may also regulate the
development of other tissues remains to be examined. In this study, we
investigate the role of Gas7 in the development of craniofacial tissues.
Knockdown of gas7 using morpholino oligomers produced abnormal phenotypes in
neural crest (NC) cells and their derivatives. NC-derived cartilage maturation
was altered in Gas7 morphants as revealed by aberrant sox9b and dlx2 expression,
a phenotype that could be rescued by coinjection of gas7 mRNA. While rhombomere
morphology remained normal in Gas7 morphants, we observed reduced expression of
the prechondrogenic genes sox9b and dlx2 in cells populating the posterior
pharyngeal arches, but the fundamental structure of pharyngeal arches was
preserved. In addition, NC cell sublineages that migrate to form neurons, glial
cells, and melanocytes were altered in Gas7 morphants as revealed by aberrant
expression of neurod, foxd3, and mitfa, respectively. Development of NC
progenitors was also examined in Gas7 morphants at 12 hpf, and we observed that
the reduction of cell precursors in Gas7 morphants was due to increased apoptosis
level. These results indicate that the formation of NC progenitors and
derivatives depends on Gas7 expression. Our observations also suggest that Gas7
regulates the formation of NC derivatives constituting the internal tissues of
pharyngeal arches, without affecting the fundamental structure of mesodermal
derived pharyngeal arches.
PMID- 26414807
TI - Synthesis, characterization, crystal structure determination and biological
screening of novel N-1 and C5 alkyl substituted scaffolds of pyrimidine.
AB - The novel N-1 and C5 alkyl substituted derivatives of pyrimidine were synthesized
by using tetrabutyl ammonium bromide (TBAB) as phase transfer catalyst at 20-25
degrees C with excellent productivity (85-95%). The new compounds were evaluated
for their antibacterial activities by screening them against Gram-positive and
Gram-negative bacterial strain: Staphylococcus aureus ATCC 6538P, Salmonella
abony NCTC 6017: Escherichia coli ATCC 8739, Staphylococcus epidermidis ATCC
12228. Among all compounds evaluated the molecule 2c and (2g-j) exhibit the most
pronounced antibacterial activity against E. coli, S. aureus and S. abony with
MICs value 25 MUg/mL.
PMID- 26414808
TI - Ligand binding studies, preliminary structure-activity relationship and detailed
mechanistic characterization of 1-phenyl-6,6-dimethyl-1,3,5-triazine-2,4-diamine
derivatives as inhibitors of Escherichia coli dihydrofolate reductase.
AB - Gram-negative bacteria are implicated in the causation of life-threatening
hospital-acquired infections. They acquire rapid resistance to multiple drugs and
available antibiotics. Hence, there is the need to discover new antibacterial
agents with novel scaffolds. For the first time, this study explores the 1,3,5
triazine-2,4-diamine and 1,2,4-triazine-2,4-diamine group of compounds as
potential inhibitors of Escherichia coli DHFR, a pivotal enzyme in the thymidine
and purine synthesis pathway. Using differential scanning fluorimetry, DSF,
fifteen compounds with various substitutions on either the 3rd or 4th positions
on the benzene group of 6,6-dimethyl-1-(benzene)-1,3,5-triazine-2,4-diamine were
shown to bind to the enzyme with varying affinities. Then, the dose dependence of
inhibition by these compounds was determined. Preliminary quantitative structure
activity relationship analysis and docking studies implicate the alkyl linker
group and the sulfonyl fluoride group in increasing the potency of inhibition. 4
[4-[3-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1-yl)phenyl]butyl]benzenesulfonyl
fluoride (NSC120927), the best hit from the study and a molecule with no reported
inhibition of E. coli DHFR, potently inhibits the enzyme with a Ki value of 42.50
+/- 5.34 nM, followed by 4-[6-[4-(4,6-diamino-2,2-dimethyl-1,3,5-triazin-1
yl)phenyl]hexyl]benzenesulfonyl fluoride (NSC132279), with a Ki value of 100.9 +/
12.7 nM. Detailed kinetic characterization of the inhibition brought about by
five small-molecule hits shows that these inhibitors bind to the dihydrofolate
binding site with preferential binding to the NADPH-bound binary form of the
enzyme. Furthermore, in search of novel diaminotriazine scaffolds, it is shown
that lamotrigine, a 1,2,4-triazine-3,5-diamine and a sodium-ion channel blocker
class of antiepileptic drug, also inhibits E. coli DHFR. This is the first
comprehensive study on the binding and inhibition brought about by
diaminotriazines of a gram-negative prokaryotic enzyme and provides valuable
insights into the SAR as an aid to the discovery of novel antibiotics.
PMID- 26414809
TI - Regenerative potential of human schneiderian membrane: progenitor cells and
epithelial-mesenchymal transition.
AB - An innate osteogenic potential of the Schneiderian membrane (SM) is progressively
assessed in studies ranging from non-human species to human subjects. It has
relevance for endosteal placement and osseointegration. Nestin-expressing
osteogenic progenitor cells are allegedly involved in bone formation and
remodelling. Nestin phenotype was not assessed previously in human SM. We
therefore aimed to fill that particular gap in the literature. Bioptic samples of
human adult SM were obtained during surgery from eight adult patients, operated
for non-malignant pathologies. Immunohistochemistry on paraffin-embedded tissue
samples used primary antibodies against nestin, CD45, CD146, cytokeratin 7 (CK7),
and alpha-smooth muscle actin (alpha-SMA). Nestin expression was consistently
found in endothelial cells, and was scarcely encountered in pericytes, putative
stromal stem/progenitor cells, as well as in glandular epithelial cells.
Moreover, woven bone formation in the periosteal layer of the SM can also be
regarded as evidence of the osteogenic potential of this membrane. Nestin and
CD45 expression in cells of the primary bone supports the osteogenic potential of
SM nestin-expressing cells and a possible involvement of hematopoietic stem cells
in maxillary sinus floor remodeling. CD146, a known inducer of epithelial
mesenchymal transition (EMT), was expressed in epithelia, as was CK7. Isolated
stromal cells were found expressing CD146, CK7 and alpha-SMA, suggesting that
regenerative processes happening in the SM may also involve processes of EMT
which generate stem/progenitor cells. This study provides additional evidence for
the regenerative potential of the Schneiderian membrane and identifies potential
roles for cells of its stem niche in osteogenesis.
PMID- 26414811
TI - Unusual High-Temperature Reversible Phase-Transition Behavior, Structures, and
Dielectric-Ferroelectric Properties of Two New Crown Ether Clathrates.
AB - Molecular ferroelectrics with high-temperature reversible phase-transition
behaviors are very rare and have currently become one of the hotspots in the
field of ferroelectric materials. Herein we display two new crown ether
clathrates possessing unusual high-temperature ferroelectric phase-transition
behaviors, cyclohexyl ammonium 18-crown-6 tetrafluoroborate (or perchlorate),
[Hcha-(18-crown-6)](+) [BF4](-) (1) and [Hcha-(18-crown-6)](+)[ClO4](-) (2) (Hcha
= protonated cyclohexyl ammonium). We have proven their reversible structural
phase transitions by variable-temperature PXRD measurements and temperature
evolutions of Raman bands. Both clathrates exhibit clear ferroelectric phase
transitions at about 397 and 390 K, respectively, revealed by the thermal
anomalies of differential scanning calorimetry (DSC) measurements, together with
abrupt dielectric anomalies in the heating and cooling processes. The
measurements on ferroelectric properties using the single crystals showed
optimized spontaneous polarization (Ps) of ca. 3.27 MUC cm(-2) for 1 and 3.78 MUC
cm(-2) for 2.
PMID- 26414810
TI - Influence of Sulfide Nanoparticles on Dissolved Mercury and Zinc Quantification
by Diffusive Gradient in Thin-Film Passive Samplers.
AB - Diffusive gradient in thin-film (DGT) passive samplers are frequently used to
monitor the concentrations of metals such as mercury and zinc in sediments and
other aquatic environments. The application of these samplers generally presumes
that they quantify only the dissolved fraction and not particle-bound metal
species that are too large to migrate into the sampler. However, metals
associated with very small nanoparticles (smaller than the pore size of DGT
samplers) can be abundant in certain environments, yet the implications of these
nanoparticles for DGT measurements are unclear. The objective of this study was
to determine how the performance of the DGT sampler is affected by the presence
of nanoparticulate species of Hg and Zn. DGT samplers were exposed to solutions
containing known amounts of dissolved Hg(II) and nanoparticulate HgS (or
dissolved Zn(II) and nanoparticulate ZnS). The amounts of Hg and Zn accumulated
onto the DGT samplers were quantified over hours to days, and the rates of
diffusion of the dissolved metal (i.e., the effective diffusion coefficient D)
into the sampler's diffusion layer were calculated and compared for solutions
containing varying concentrations of nanoparticles. The results suggested that
the nanoparticles deposited on the surface of the samplers might have acted as
sorbents, slowing the migration of the dissolved species into the samplers. The
consequence was that the DGT sampler data underestimated the dissolved metal
concentration in the solution. In addition, X-ray absorption spectroscopy was
employed to determine the speciation of the Hg accumulated on the sampler binding
layer, and the results indicated that HgS nanoparticles did not appear to
directly contribute to the DGT measurement. Overall, our findings suggest that
the deployment of DGT samplers in settings where nanoparticles are relevant
(e.g., sediments) may result in DGT data that incorrectly estimated the dissolved
metal concentrations. Models for metal uptake into the sampler may need to be
reconsidered.
PMID- 26414812
TI - Low testosterone as a better predictor of mortality than sarcopenia in men with
advanced liver disease.
AB - BACKGROUND AND AIM: Both sarcopenia and low serum testosterone have been
associated with increased mortality in men with cirrhosis. It is not known how
these variables interact. METHODS: We conducted a retrospective longitudinal
cohort study of 145 men referred for liver transplant evaluation between 2005 and
2012. Baseline demographics included hormone profile and model of end-stage liver
disease (MELD) score. Baseline computerized tomography was reformatted to
calculate skeletal muscle area at L4 using validated, Tomovision software-based
methodology. The primary outcome was time to death or liver transplantation.
RESULTS: Median testosterone was low at 6.2 nmol/L (ref. 10-27.6 nmol/L) as was
muscle mass at 48.0 cm(2)/m(2) (ref. > 52.4 cm(2)/m(2)). Muscle mass correlated
with both serum testosterone (tau = 0.132, P = 0.019) and MELD score (tau =
0.155, P = 0.007). In separate multivariable models, both sarcopenia (hazard
ratio [HR] 1.05, P = 0.04) and low testosterone (HR 1.08, P = 0.01) were
significantly associated with mortality independent of MELD score. When the
variables MELD score, muscle area, and testosterone were entered into a single
model, low testosterone but not sarcopenia remained significantly predictive of
mortality (HR 1.07, P = 0.02, and HR 1.04, P = 0.09, respectively). CONCLUSION:
Low testosterone and sarcopenia are both associated with increased mortality in
men with advanced liver disease and may identify patients at high risk of
mortality that would be missed by the MELD score alone. Low testosterone appears
to be a better predictor of mortality than sarcopenia and is a simpler test to
improve the prognostic value of the MELD score. Interventional trials are
required to determine whether low testosterone and sarcopenia are markers or
mediators of mortality in this population.
PMID- 26414813
TI - Enantioselective Functionalization of Inactive sp(3) C-H Bonds Remote to
Functional Group by Metal/Organo Cooperative Catalysis.
AB - A metal/organo cooperative catalysis to enable the enantioselective
functionalization of inactive C-H bonds gamma to the formyl group in aliphatic
aldehydes has been established. Instead of using enals as substrates in
traditional organocatalytic cyclization reactions, the aliphatic aldehydes
directly participated in [4 + 2] cyclization with quinone derivatives exploiting
molecular oxygen as oxidants to afford optically active cyclic molecules with
excellent levels of enantioselectivity. This method features a combination of
pot, step, and atom economy.
PMID- 26414815
TI - The Foundation of International Surgery.
PMID- 26414814
TI - Meeting the Mental Health Needs of the Homebound: A Psychiatric Consult Service
Within a Home-Based Primary Care Program.
AB - The growing population of homebound adults increasingly receives home-based
primary care (HBPC) services. These patients are predominantly frail older adults
who are homebound because of multiple medical comorbidities, yet they often also
have psychiatric diagnoses requiring mental health care. Unfortunately, in-home
psychiatric services are rarely available to homebound patients. To address unmet
psychiatric need among the homebound patients enrolled in our large academic HBPC
program, we piloted a psychiatric in-home consultation service. During our 16
month pilot, 10% of all enrolled HBPC patients were referred for and received
psychiatric consultation. Depression and anxiety were among the most common
reasons for referral. To better meet patients' medical and psychiatric needs,
HBPC programs need to consider strategies to incorporate psychiatric services
into their routine care plans.
PMID- 26414817
TI - Clinical Role of Modified Seton Procedure and Coring Out for Treatment of Complex
Anal Fistulas Associated With Hidradenitis Suppurativa.
AB - A variety of techniques have been described to treat complex anal fistulas. When
complex anal fistulas are associated with hidradenitis suppurativa, the treatment
has to be appropriately tailored for the severity and distribution of the disease
so as to remove the external fistula tract to prevent recurrence while ensuring
fecal continence. Between 2007 and 2011, a total of 10 males (ranging in age from
32 to 54 years) complained of recurrent purulent discharge in the buttocks and
thigh regions. The discharge had started about 12 to 18 months prior, and had
increased progressively resulting in complex anal fistulas and hidradenitis
suppurativa in the buttocks. They underwent surgical operation according to a
modified seton procedure for complex anal fistulas and coring out for
hidradenitis suppurativa. They were discharged from the hospital in 4 to 5 days,
while the seton dropped spontaneously about 6 to 8 months after surgery. They
have been well without any morbidities or recurrence. The present paper
demonstrates that cases of complex anal fistulas associated with hidradenitis
suppurativa can be successfully treated with a modified seton procedure and
coring out of hidradenitis suppurativa.
PMID- 26414816
TI - Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer: Does Time to Surgery
Matter?
AB - The objective of this paper was to evaluate whether delaying surgery following
long-course chemoradiotherapy for rectal cancer correlates with pathologic
complete response. Pre-operative chemoradiotherapy (CRT) is standard practice in
the UK for the management of locally advanced rectal cancer. Optimal timing of
surgery following CRT is still not clearly defined. All patients with a diagnosis
of rectal cancer who had undergone long-course CRT prior to surgery between
January 2008 and December 2011 were included. Statistical analysis was performed
using Stata 11. Fifty-nine patients received long-course CRT prior to surgery in
the selected period. Twenty-seven percent (16/59) of patients showed a complete
histopathologic response and 59.3% (35/59) of patients had tumor down-staging
from radiologically-assessed node positive to histologically-proven node negative
disease. There was no statistically significant delay to surgery after completion
of CRT in the 16 patients with complete response (CR) compared with the rest of
the group [IR: incomplete response; CR group median: 74.5 days (IQR: 70-87.5) and
IR group median: 72 days (IQR: 57-83), P = 0.470]. Although no statistically
significant predictors of either complete response or tumor nodal status down
staging were identified in logistic regression analyses, a trend toward complete
response was seen with longer delay to surgery following completion of long
course CRT.
PMID- 26414818
TI - Pneumoretroperitoneum and Pneumomediastinum Revealing a Left Colon Perforation.
AB - Left colon perforation usually occurs in complicated diverticulitis or cancer.
The most frequent signs are intraperitoneal abscess or peritonitis. In cases of
retroperitoneal colonic perforation, diagnosis may be difficult. A 59-year-old
woman presented with left thigh pain and with abdominal discomfort associated
with mild dyspnea. Computed tomography scan showed air bubbles and purulent
collection in the retroperitoneum, with subcutaneous emphysema extending from the
left thigh to the neck. Computed tomography scan also revealed portal vein gas
and thrombosis with multiple liver abscesses. An emergency laparotomy revealed a
perforation of the proximal left colon. No masses were found. A left colectomy
was performed. The retroperitoneum was drained and washed extensively. A negative
pressure wound therapy was applied. A second-look laparotomy was performed 48
hours later. The retroperitoneum was drained and an end colostomy was performed.
Intensive Care Unit postoperative stay was 9 days, and the patient was discharged
on the 32nd postoperative day. Pneumoretroperitoneum and pneumomediastinum are
rare signs of colonic retroperitoneal perforation. The diagnosis may be delayed,
especially in the absence of peritoneal irritation. Clinical, laboratory, and
especially radiologic parameters might be useful. Surgical treatment must be
prompt to improve prognosis.
PMID- 26414819
TI - Effect of Intraoperative Valsalva Maneuver Application on Bleeding Point
Detection and Postoperative Drainage After Thyroidectomy Surgeries.
AB - The purpose of this paper was to analyze the effect of Valsalva maneuver
application before finalizing thyroidectomy operations on the identification of
bleeding points and postoperational drainage. One hundred patients (age range, 24
76 years) with multinodular goiter, recurrent multinodular goiter, toxic diffuse
multinodular goiter, or papillary thyroid cancer were included in the study and
were divided into 2 groups of 50 randomly. Both groups underwent thyroidectomy
operation, only 1 group received intraoperative Valsalva maneuver application
(twice, 30 seconds of 30-cm PEEP). The size of the thyroid gland, the duration of
operation, hospital stay, and drain usage were reported. Postoperational
occurrences of drainage, hematoma, reoperation, and additional complications were
compared between the groups. Valsalva maneuver application helped to identify
minor bleeding points in 32% of the cases. There was no significant difference
between the study groups regarding the thyroid gland size, operation duration,
hospital stay, and the duration of drain usage (P > 0.05 for all). The amount of
drainage as well as the frequencies of hematoma, reoperation, and further
complications was not significantly different between the study groups (P > 0.05
for all). Intraoperative application of Valsalva maneuver is only useful to
detect minor bleeding points in some patients during thyroidectomy operations,
but it had no effect on the duration of postoperative drain usage, the amount of
drainage, and risk of hematoma. Therefore, intraoperative application of Valsalva
maneuver has no beneficial effect on postoperative hemorrhagic complication after
thyroidectomy operations.
PMID- 26414820
TI - Prevention of Incisional Surgical Site Infection Using a Subcuticular Absorbable
Suture in Elective Surgery for Gastrointestinal Cancer.
AB - This study examined whether subcuticular absorbable sutures actually reduce
incisional SSI in patients undergoing surgery for gastrointestinal (GI) cancer.
Surgical site infection (SSI) is still a source of major complications in
digestive tract surgery. Reportedly, incisional SSI can be reduced using
subcuticular suturing. We performed subcuticular suturing using a 4-0 absorbable
monofilament in patients undergoing elective surgery for GI cancer beginning in
2008. Using an interrupted technique, sutures were placed 1.5-2.0cm from the edge
of the wound, with everted subcuticular sutures created at intervals of 1.5
2.0cm. The control group consisted of cases in which the common subcutaneous
suture method using clip. One hundred cases were examined in the subcuticular
group. The incidence of SSI was 0% in the subcuticular suture group, compared
with 13.9% in the control group; this difference was significant. Incisional SSI
can be prevented using the devised subcuticular absorbable sutures in patients
undergoing elective surgery for GI cancer.
PMID- 26414821
TI - Delayed Appendectomy Is Safe in Patients With Acute Nonperforated Appendicitis.
AB - The present study examined whether acute, nonperforated appendicitis is a
surgical emergency requiring immediate intervention or a disease that can be
treated with a semielective operation. Immediate appendectomy has been the gold
standard in the treatment of acute appendicitis because of the risk of pathologic
progression. However, this time-honored practice has been recently challenged by
studies suggesting that appendectomies can be elective in some cases and still
result in positive outcomes. This was a retrospective study using the charts of
patients who underwent an appendectomy for acute, nonperforated appendicitis
between January 2007 and February 2012. Patients were divided into 2 groups for
comparison: an immediate group (those who were moved to an operating room within
12 hours after hospital arrival) and a delayed group (those within 12 to 24 hours
after hospital arrival). The end points were conversion rate, operative time,
perforation rate, complication rate, readmission rate, length of hospital stay,
and medical costs. Of 1805 patients, 1342 (74.3%) underwent immediate operation
within 12 hours after hospital arrival, whereas 463 (25.7%) underwent delayed
operation within 12 to 24 hours. There were no significant differences in open
conversion, operative time, perforation, postoperative complications, and
readmission between the 2 groups. Length of hospital stay was significantly
greater (3.7 +/- 1.7 days) and medical costs were also greater [$2346.30 +/-
$735.30 (US dollars)] in the delayed group than in the immediate group [3.1 +/-
1.9 days; P = 0.000 and $2257.80 +/- $723.80 (US dollars); P = 0.026]. Delayed
appendectomy is safe for patients with acute nonperforated appendicitis.
PMID- 26414822
TI - Solitary Hepatic Eosinophilic Granuloma Accompanied by Eosinophilia Without
Parasitosis: Report of a Case.
AB - A 43-year-old Japanese woman visited for a hepatic tumor incidentally found. We
suspected eosinophilic granuloma of the liver (EGL) due to visceral larva migrans
(VLM). However, neither past history nor medical interview indicated a risk of
parasitosis. Blood testing revealed eosinophilia, serum examination showed normal
results for immunoglobulin E, and enzyme-linked immunosorbent assay yielded
negative for Toxocara and Anisakis. Gastric and colonic endoscopy revealed normal
features. Several imagings showed central necrosis of the tumor. After informed
consent, laparoscopic resection was performed. Histopathological examination
showed EGL without parasites. No recurrence had occurred postoperatively. Most
reports documented that EGL are caused by VLM. However, parasites are not always
demonstrable on serum, histopathological, or immunochemical examinations. When
acting as allergens to induce type I responses, microscopic agents other than
parasites in the intestinal tract could induce eosinophilic inflammation in the
liver. Accumulation of more cases should help clarify other pathogeneses for EGL.
PMID- 26414823
TI - Giant Extra-Adrenal Retroperitoneal Myelolipoma With Incidental Gastric
Mesenchymal Neoplasias.
AB - Extra-adrenal myelolipomas are rare, benign tumors composed of adipose tissue and
hematopoietic cells. Almost all myelolipomas occur within the adrenal gland. Only
50 cases of myelolipomas were described in literature and none of these were
associated with gastric mesenchymal neoplasia. A 72-year-old male patient
presented to a family medicine outpatient clinic with dyspnea and urinary
urgency. His abdominal sonography revealed a 9-cm intra-abdominal mass. An
incidental finding was 2 separate masses 1 cm each on the serosal surface of the
stomach. The pathology specimen of the retroperitoneal mass revealed myelolipoma
histopathology while gastric masses were reported as spindle cell mesenchymal
neoplasias. The association of gastric spindle cell tumor and myelolipoma was not
reported before in medical literature. Extra-adrenal myelolipomas are rare
lesions, but should be considered in the differential diagnosis of fat containing
retroperitoneal masses that are well circumscribed.
PMID- 26414824
TI - Management of Appendiceal Mass and Abscess. An 11-Year Experience.
AB - The aim of our study is to compare the results of emergency surgery versus
conservative treatment with interval surgery in patients diagnosed with
appendiceal mass and abscess. A retrospective review of 48 patients with
appendiceal mass and abscess treated from January 2002 to January 2013 at General
Surgery Department of Kipshidze Central University Hospital was performed.
Patients with emergency surgery were compared to patients treated by nonoperative
management with interval surgery. Demographics, clinical profile, and operative
outcomes were studied. The emergency surgery group included 25 patients, and the
interval surgery group included 23 patients. The clinical characteristics of the
emergency surgery and interval surgery groups were not statistically different.
In the emergency surgery group, an open appendectomy was performed on 17
patients, and colonic resections (ileocecectomy or right hemicolectomy) were
performed on 8 patients. In the interval surgery group, an open appendectomy was
performed on 21 patients, and colonic resections were performed on 2 patients.
There were no statistical differences in types of surgery, postoperative
complications, operation time without colonic resections, and postoperative
hospitalization period among these 2 groups. Operation time with colonic
resections was of greater duration in the emergency surgery group than in the
interval surgery group (P = 0.04). Both treatment methods for appendiceal mass
and abscess have the same results. The surgeon must consider clinical symptoms
and results of investigations in each particular case when choosing an
appropriate treatment method. Prospective randomized controlled trials are
required for comparing the results of all 3 treatment methods of appendiceal
mass.
PMID- 26414825
TI - Surgical Mortality Audit-lessons Learned in a Developing Nation.
AB - Surgical audit is a systematic, critical analysis of the quality of surgical care
that is reviewed by peers against explicit criteria or recognized standards. It
is used to improve surgical practice with the ultimate goal of improving patient
care. As the pattern of surgical care is different in the developing world, we
analyzed mortalities in a referral medical institute of India to suggest
interventions for improvement. An analysis of total admissions, different
surgeries, and mortalities over 1 year in an urban referral medical institute of
northern India was performed, followed by "peer review" of the mortalities.
Mortality rates as outcomes and classification was done to provide comparative
results. Of 10,005 surgical patients, 337 (male = 221, female = 116) deaths were
reported over 1 year. The overall mortality rate was 3.36%, while mortality in
operative cases was 1.76%. Total deaths were classified into (1) Viable: 153
(45%), (2) Nonviable: 174 (52%), and (3) Indeterminate: 10 (3%). Exclusion of the
nonviable group reduced the mortality rate from 3.36% to 1.62%. Trauma was the
major cause of mortality (n = 235; 70%) as compared to other surgical patients (n
= 102; 30%). Increased mortality was also associated with emergency procedures
(3.66%) as compared to elective surgeries (0.34%). In conclusion, audit of
mortality and morbidity helps in initiating and implementing preventive
strategies to improve surgical practice and patient care, and to reduce mortality
rates. The mortality and morbidity forum is an important educational activity. It
should be considered a mandatory activity in all postgraduate training programs.
PMID- 26414826
TI - Skeletonization and Isolation of the Glissonean and Venous Branches in Liver
Surgery With an Ultrasonic Scalpel Technology.
AB - This study describes a novel technique for skeletonization and isolation of
Glissonean and venous branches during liver surgery using a harmonic scalpel
(HS). Hepatic resections with HS were performed with the skeletonization and
isolation technique in 50 patients (HS group). Variables evaluated were blood
loss, operative time, biliary leak, and morbidity. The results were compared with
50 hepatic resections that were performed using a previously established
technique: Cavitron ultrasonic surgical aspirator with electric cautery,
ligatures, and hemoclips (NHS group). The HS group had shorter total operative
times (285 versus 358 minutes; P = 0.01), less blood loss (389 versus 871 mL; P =
0.034), and less crystalloid infusion (2744 versus 3299 mL; P = 0.027) compared
with the NHS group. Postoperative liver function and complication rates were
similar when comparing the two groups. These data demonstrate that HS is a
simple, easy, and effective instrument for the skeletonization and isolation of
vessels during liver transection.
PMID- 26414827
TI - A Left-Sided Approach for Resection of Hepatic Caudate Lobe Hemangioma: Two Case
Reports and a Literature Review.
AB - Resection of the hemangioma located in the caudate lobe is a major challenge in
current liver surgery. This study aimed to present our surgical technique for
this condition. Two consecutive patients with symptomatic hepatic hemangioma
undergoing caudate lobectomy were investigated retrospectively. First, all the
blood inflow of hemangioma from the portal vein and the hepatic artery at the
base of the umbilical fissure was dissected. After the tumors became soft and
tender, the short hepatic veins and the ligaments between the secondary porta
hepatis were severed. At last the tumors were resected from the right lobe of the
liver. The whole process was finished by a left-sided approach. Blood lost in
Case 1 was 1650 mL because of ligature failing in one short hepatic vein, and in
the other case, 210 mL. Operation time was 236 minutes and 130 minutes,
respectively. Postoperative hospital stays were 11 and 5 days, respectively. The
diameter of tumors was 9.0 cm and 6.5 cm. Case 1 required blood transfusion
during surgery. No complications such as biliary fistula, postoperative bleeding,
and liver failure occurred. The left-sided approach produced the best results for
caudate lobe resection in our cases. The patients who recovered are living well
and asymptomatic. Caudate lobectomy can be performed safely and quickly by a left
sided approach, which is carried out with optimized perioperative management and
innovative surgical technique.
PMID- 26414829
TI - Splenic Artery Pseudoaneurysm Masquerading as a Pancreatic Cyst-A Diagnostic
Challenge.
AB - Splenic artery pseudoaneurysm is a rare entity. Clinical diagnosis is challenging
because presentation is often varied. It can range from an incidental finding to
hemodynamic collapse from sudden rupture and bleeding. The most common cause of
this condition is pancreatitis. We report an unusual case of a young man not
known to have pancreatitis who presented with hematemesis with normal
esophagogastroduodenoscopy. Imaging modalities did not lead to a definitive
diagnosis, and he underwent emergency laparotomy with surgical ligation of
splenic artery pseudoaneurysm for hemodynamic instability, without a definitive
preoperative diagnosis.
PMID- 26414828
TI - Intraductal Papillary Mucinous Neoplasm of the Pancreas: Current Perspectives.
AB - In this article, we aimed to review the literature on the clinics and management
of intraductal papillary mucinous neoplasm (IPMN). Intraductal papillary mucinous
neoplasm of the pancreas is a mucin-producing cystic mass originating from the
pancreatic ductal system. Approximately 25% of the pancreatic neoplasms resected
surgically and 50% of pancreatic cysts detected incidentally are IPMNs. They can
be benign or malignant in character, while malignant transformation of benign
forms can be encountered. It is important to determine IPMNs in the early stages,
implementation of appropriate treatment approaches, and follow-up to provide
better prognosis. We reviewed the studies published in the English medical
literature through PubMed and summarized the clinical features and current
approaches to the treatment and follow-up of the IPMN. Due to the recent advances
and widespread implementation of radiological imaging techniques, the incidental
detection rate of IPMNs has increased significantly. The effective treatment of
the disease is possible via the detailed diagnosis of the disease, determination
of the prognostic factors, and a multidisciplinary approach. Recent literature
also emphasized the molecular profile determination approaches for assessment of
prognosis of patients with IPMN. Current knowledge on IPMN, a clinically
important epidemiologic problem, shows that the treatment should be personalized
considering the prognostic features and life expectancy of the patient.
PMID- 26414830
TI - A Promising Method for Repairing Low-Level Biliary Strictures After
Cholecystectomy.
AB - The purpose of this study is to introduce and evaluate a new technique of
repairing bile ducts by the tubular gastric wall with a vascularized pedicle.
Both the end-to-end bile duct repair and Roux-en-Y hepatoenterostomy have
limitations in the treatment of benign bile duct strictures after
cholecystectomy. There are no other good choices to manage these cases,
especially the bile duct transection injuries or partly missing common bile duct
or hepatic duct. Eleven patients with partly missing common bile ducts in the
Chinese People's Liberation Army General Hospital between January 2007 and
December 2012 were retrospectively analyzed. The study comprised 8 females and 3
males, whose age ranged from 29 to 56 years. All patients underwent successful
bile duct repair. The time of operations ranged from 210 minutes to 240 minutes.
The maximal blood loss was less than 220 ml. There was no perioperative mortality
and no case of gastric fistula. Postoperative complications occurred in 3
patients, including wound infection, bile leakage, and erosive gastritis. All
complications were cured by conservative treatment. The mean follow-up time was
42 months. One patient was classified as Terblanche's grade II and 10 patients
were classified as Terblanche's grade I. The observations indicate that this
technique is a feasible and effective choice to manage low level biliary
stricture after cholecystectomy, especially suitable to repair bile duct
transection injuries or partly missing common bile duct or hepatic duct.
PMID- 26414831
TI - Pancreatic Follicular Lymphoma Presenting as Acute Pancreatitis: Report of a
Case.
AB - Pancreatic B-cell lymphoma is rare; it accounts for 0.2% to 2.0% of extranodal
non-Hodgkin lymphoma, and constitutes less than 0.5% of all pancreatic
malignancies. Most histologic types of the pancreatic lymphoma are diffuse large
B-cell lymphoma, and follicular lymphoma is quite rare. We report here a case of
pancreatic follicular lymphoma that was initially detected by acute pancreatitis.
This is the first reported case of pancreatic follicular lymphoma presenting with
acute pancreatitis. A 71-year-old woman had epigastric and left upper quadrant
abdominal pain. Computed tomography (CT) revealed features of acute pancreatitis.
After standard therapy for pancreatitis, enhanced CT showed a pancreatic tumor
(50 * 35 mm) in the body of the pancreas with gradual enhancement. Endoscopic
retrograde cholangiopancreatography and magnetic resonance
cholangiopancreatography showed a complete interruption of the pancreatic duct in
the body, with mild dilation of the duct in the tail of the pancreas. Endoscopic
ultrasonography revealed hypervascularity of the pancreatic tumor. The patient
underwent distal pancreatectomy to remove the cause of pancreatitis and to
disclose the diagnosis. Histologic examination revealed follicular lymphoma of
pancreas. Despite recent improvement in clinical strategies, differential
diagnosis between pancreatic lymphoma and pancreatic cancer is still difficult
without histologic information. Pancreatic lymphoma should be considered as a
differential diagnosis in a patient who initially presents with acute
pancreatitis.
PMID- 26414832
TI - Application of a Z-Shaped Umbilical Incision and a Saline-Cooled Radiofrequency
Device to Single-Incision Laparoscopic Surgery for a Huge Liver Cyst: Report of a
Case.
AB - When compared with other diseases, few authors have reported on single-incision
laparoscopic surgery (SILS) for liver cysts. We herein describe our experience
with SILS for a huge liver cyst with the application of an umbilical Z-shaped
incision using a gel port and a high-density monopolar saline-cooled
radiofrequency device with a successful outcome. An 80-old-year woman was
diagnosed with a huge liver cyst with abdominal pain. She underwent percutaneous
drainage of the liver cyst and injection of both absolute ethanol and an
antimicrobial agent into the liver cyst at the previous hospital. Because of re
expansion of the liver cyst and symptom recurrence, we performed SILS for the
liver cyst. An umbilical Z-shaped incision was made for gel port placement. After
aspiration of the cystic fluid and dissection of the thin cystic wall by
laparoscopic coagulating shears, the thick cystic wall was divided using an
endoscopic linear stapler to avoid bleeding and bile leakage. After wide
fenestration, a high-density monopolar saline-cooled radiofrequency device was
applied for the ablation of the remnant membrane of the cystic wall. All
maneuvers could be performed only through the gel port. The patient was
discharged 4 days after surgery and was satisfied with the cosmetic results. This
case shows that the application of an umbilical Z-shaped incision using a gel
port and a high-density monopolar saline-cooled radiofrequency device is useful
for the accomplishment of SILS for a huge liver cyst.
PMID- 26414833
TI - Palliation With Endoscopic Metal Stents May Be Preferable to Surgical
Intervention for Patients With Obstructive Pancreatic Head Adenocarcinoma.
AB - The aim of this study was to evaluate the efficacy of endoscopically placed metal
stents in comparison with operative procedures, in patients with obstructive
pancreatic head cancer. Endoscopic stenting techniques and materials for
gastrointestinal malignancies are constantly improving. Despite this evolution,
many still consider operative procedures to be the gold standard for palliation
in patients with unresectable obstructive pancreatic head cancer. This is a
retrospective study of 52 patients who were diagnosed with obstructive (biliary,
duodenal, or both) adenocarcinoma of the pancreatic head. Twenty-nine patients
(endoscopy group) underwent endoscopic stenting. Eleven patients (bypass group)
underwent biliodigestive bypass. Twelve patients (Whipple group) underwent
Whipple operation with curative intent; however, histopathology revealed R1
resection (palliative Whipple). T4 disease was identified in 13 (44.8%), 7
(63.6%), and 3 (25%) patients in the endoscopy, bypass, and Whipple groups,
respectively. Metastatic disease was present only in the endoscopy group (n = 12;
41.3%). There was no intervention-related mortality. Median survival was 280 days
[95% confidence interval (95% CI), 103, 456 days], 157 days (95% CI, 0, 411
days), and 647 days (95% CI, 300, 993 days) for the endoscopy, bypass, and
Whipple groups, respectively (P = 0.111). In patients with obstructive pancreatic
head cancer, endoscopic stenting may offer equally good palliation compared with
surgical double bypass. The numerically (not statistically) better survival after
palliative Whipple might be explained by the smaller tumor burden in this
subgroup of patients and not by the superior efficacy of this operation.
PMID- 26414834
TI - Giant Cholangiolocellular Carcinoma With Early Recurrence That Was Difficult to
Distinguish From Cholangiocellular Carcinoma: Report of a Case.
AB - Cholangiolocellular carcinoma (CoCC) is a rare type of malignant liver tumor
derived from hepatic stem cells, which exist in the canals of Hering. However,
the characteristics of CoCC have not been clarified. In general, CoCC is
associated with a better prognosis than cholangiocellular carcinoma (CCC). Here,
we report a case of giant CoCC, which was difficult to distinguish from CCC and
showed early recurrence and necrosis inside the tumor. A 59-year-old man was
diagnosed with CCC based on preoperative imaging. The diameter of the tumor was
approximately 14 cm, and he subsequently underwent extended right lobectomy of
the liver. Histopathologic analysis revealed that tumor cells proliferated and
replaced the surrounding normal liver cell cords in front of the tumor.
Furthermore, the tumor cells were positive for cytokeratin 19 and epithelial
membrane antigen. Epithelial membrane antigen staining pattern was positive on
the membranous area of the lumen. Therefore, the tumor was diagnosed as CoCC.
Although adjuvant chemotherapy was performed, intrahepatic recurrence occurred at
4 months after surgery. We present here the novel characteristics of CoCC that
show early recurrence and necrosis within the tumor. These characteristics have
not previously been reported in patients with CoCC.
PMID- 26414835
TI - Comparison of Anterior Versus Posterior Approach in the Treatment of
Thoracolumbar Fractures: A Systematic Review.
AB - Despite extensive research on thoracolumbar fractures, controversy still exists
about which approach is the most appropriate. Lack of evidence-based practice may
result in patients being treated inappropriately. The objective of study was to
perform a systematic review of the effectiveness of the anterior and posterior
approaches in the treatment of thoracolumbar fractures. We conducted searches of
PubMed and the Cochrane Library, searching for relevant trials up to August 2013
that compared anterior and posterior for the treatment of thoracolumbar
fractures. The key words "anterior," "posterior," "thoracolumbar fracture,"
"CCT," and "RCT" were used. We assessed all included literature by using the
Cochrane handbook (version 5.1). The results were expressed as the mean
difference for continuous outcomes and risk difference for dichotomous outcomes,
with a 95% confidence interval, using RevMan version 5.2. There were 3 randomized
controlled trials and 11 clinical controlled trials included. The meta-analysis
showed no significant difference between groups regarding Cobb angle, the Frankel
scale, ASIA/JOA motor score, complications, and number of patients returning to
work. Compared with the anterior approach, the posterior approach demonstrated
superior canal decompression. In the burst fracture subgroup, operative times
were significantly shorter and perioperative blood loss was less in the posterior
approach group. The posterior approach is more effective for canal decompression,
operative times, and perioperative blood loss. However, because of the lack of
randomized controlled trials, and because of large sample size studies,
heterogeneity was significant between reports. The optimal treatment for
thoracolumbar fractures requires further study.
PMID- 26414836
TI - Three-Dimensional Laparoscopic Sleeve Gastrectomy: Improved Patient Safety and
Surgeon Convenience.
AB - One of the aims of laparoscopic surgery is to improve upon the results obtained
by open surgery. This clearly appears to have been achieved in bariatric surgery.
Two-dimensional (2-D) systems have been used to date, though new 3-dimensional (3
D) technologies have been introduced in an attempt to improve surgeon vision and
thus increase the safety of the surgical techniques. Sixty obese patients
underwent sleeve gastrectomy using a device equipped with 3-D optics allowing
surgery to be viewed by the surgeon in 3 dimensions by using a specific monitor
and wearing appropriate glasses. The mean patient age was 48.1 years. The mean
weight was 114 kg (range, 92-172), with a mean body mass index (BMI) of 44 +/-
5.21 kg/m(2). All surgeries were performed using the 3-D system, with a mean
surgical time of 71 +/- 49.6 minutes and a mean hospital stay of 3.0 +/- 1.2
days. Only 1 intraoperative complication was recorded: retroperitoneal bleeding
on insertion of the optical trocar. Over a mean follow-up period of 12 months,
the mean body weight of the patients was 88 kg (range, 71-121), with a BMI of
30.56 +/- 3.98 kg/m(2) and a percentage excess weight loss of 68.14% +/- 7.89%.
There was clear improvement of both the blood pressure and glucose levels. Three
dimensional sleeve gastrectomy is safe, viable, and fully reproducible compared
with 2-D surgery, improving visualization of the surgical field, safety, and
surgeon convenience. Randomized studies involving larger patient samples are
needed for the comparison of results.
PMID- 26414837
TI - Phase I Dose-Escalation Study of Docetaxel, Cisplatin, and 5-Fluorouracil
Combination Chemotherapy in Patients With Advanced Esophageal Carcinoma.
AB - A dose-escalation study of docetaxel (DOC), cisplatin (CDDP), and 5-fluorouracil
(5-FU; DCF combination regimen) was performed to determine the maximum-tolerated
dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLT) in advanced
esophageal carcinoma. Eighteen patients with esophageal carcinoma were enrolled
and received DCF combination therapy at different dose levels. DLTs included
febrile neutropenia and oral mucositis. DLT occurred in 2 out of 6 patients at
level 2 and 3. The study proceeded to level 4, according to the protocol. The
level 4 dose was defined as the MTD and the level 3 dose was defined as the RD.
The RD for DCF combination chemotherapy for advanced esophageal carcinoma in the
present study was 70 mg/m(2) DOC plus 70 mg/m(2) CDDP on day 1 plus 700 mg/m(2) 5
FU on days 1-5 at 4-week intervals. This regimen was tolerable and highly active.
A phase II study has been started.
PMID- 26414839
TI - It was(n't) me: Exercising restraint when choices appear self-diagnostic.
AB - This research tests the hypothesis that individuals exercise restraint for
actions that reflect on their self-concept (i.e., self-diagnostic actions).
Experiments 1 and 2 show an action framed as occurring at the beginning or end
(vs. middle) of a constructed sequence is seen as more self-diagnostic.
Accordingly, Experiment 3 finds more restraint in snack choices at the framed
beginning or end (vs. middle). Furthermore, the degree of importance of a goal
which reflects its centrality to the self-concept-determines responses to self
diagnosticity cues such as framed positions. Specifically, participants committed
to financial goals (Experiment 4) and health goals (Experiment 5) were more
likely to make decisions consistent with these goals at the beginning or end, but
indulged and splurged in the middle. Experiment 6 shows similar patterns for
judgments of magazine subscriptions, but only when individuals are faced with a
decision that poses a self-control conflict for them. These results highlight the
role of the self in self-control by demonstrating that people exercise restraint
when decision contexts seem more telling of the self.
PMID- 26414841
TI - Sowing the seeds of stereotypes: Spontaneous inferences about groups.
AB - Although dispositional inferences may be consciously drawn from the trait
implications of observed behavior, abundant research has shown that people also
spontaneously infer trait dispositions simply in the process of comprehending
behavior. These spontaneous trait inferences (STIs) can occur without intention
or awareness. All research on STIs has studied STIs based on behaviors of
individual persons. Yet important aspects of social life occur in groups, and
people regularly perceive groups engaging in coordinated action. We propose that
perceivers make spontaneous trait inferences about groups (STIGs), parallel to
the STIs formed about individuals. In 5 experiments we showed that (a) perceivers
made STIGs comparable with STIs about individuals (based on the same behaviors),
(b) a cognitive load manipulation did not affect the occurrence of STIGs, (c)
STIGs occurred for groups varying in entitativity, (d) STIGs influenced
perceivers' impression ratings of those groups, and (e) STIG-based group
impressions generalized to new group members. These experiments provide the first
evidence for STIGs, a process that may contribute to the formation of spontaneous
group impressions. Implications for stereotype formation are discussed.
PMID- 26414840
TI - The scope and consequences of metaphoric thinking: Using individual differences
in metaphor usage to understand how metaphor functions.
AB - People often think, feel, and behave metaphorically according to conceptual
metaphor theory. There are normative sources of support for this theory, but
individual differences have received scant attention. This is surprising because
people are likely to differ in the frequency with which they use metaphors and,
therefore, the frequency with which they experience the costs and benefits of
metaphoric thinking. To investigate these ideas, a 5-study program of research
(total N = 532) was conducted. Study 1 developed and validated a Metaphor Usage
Measure (MUM), finding that people were fairly consistent in their tendencies
toward literal thought and language on the one hand versus metaphoric thought and
language on the other. These differences were, in turn, consequential. Although
metaphor usage predicted susceptibility to metaphor transfer effects (Studies 2
and 3), it was also linked to higher levels of emotional understanding (Studies 4
and 5). The findings provide support for several key premises of conceptual
metaphor theory in the context of a new measure that can be used to track the
consequences of metaphoric thinking. (PsycINFO Database Record
PMID- 26414842
TI - Cognitive adaptations to stressful environments: When childhood adversity
enhances adult executive function.
AB - Can growing up in a stressful childhood environment enhance certain cognitive
functions? Drawing participants from higher-income and lower-income backgrounds,
we tested how adults who grew up in harsh or unpredictable environments fared on
2 types of executive function tasks: inhibition and shifting. People who
experienced unpredictable childhoods performed worse at inhibition (overriding
dominant responses), but performed better at shifting (efficiently switching
between different tasks). This finding is consistent with the notion that
shifting, but not inhibition, is especially useful in unpredictable environments.
Importantly, differences in executive function between people who experienced
unpredictable versus predictable childhoods emerged only when they were tested in
uncertain contexts. This catalyst suggests that some individual differences
related to early life experience are manifested under conditions of uncertainty
in adulthood. Viewed as a whole, these findings indicate that adverse childhood
environments do not universally impair mental functioning, but can actually
enhance specific types of cognitive performance in the face of uncertainty.
PMID- 26414843
TI - Men as cultural ideals: Cultural values moderate gender stereotype content.
AB - Four studies tested whether cultural values moderate the content of gender
stereotypes, such that male stereotypes more closely align with core cultural
values (specifically, individualism vs. collectivism) than do female stereotypes.
In Studies 1 and 2, using different measures, Americans rated men as less
collectivistic than women, whereas Koreans rated men as more collectivistic than
women. In Study 3, bicultural Korean Americans who completed a survey in English
about American targets rated men as less collectivistic than women, whereas those
who completed the survey in Korean about Korean targets did not, demonstrating
how cultural frames influence gender stereotype content. Study 4 established
generalizability by reanalyzing Williams and Best's (1990) cross-national gender
stereotype data across 26 nations. National individualism-collectivism scores
predicted viewing collectivistic traits as more-and individualistic traits as
less-stereotypically masculine. Taken together, these data offer support for the
cultural moderation of gender stereotypes hypothesis, qualifying past conclusions
about the universality of gender stereotype content.
PMID- 26414844
TI - Systems of meaning and transference: Implicit significant-other activation evokes
shared reality.
AB - Evidence shows that representations of significant others (SOs) are used in
interpersonal relations-for example, in the social-cognitive process of
transference (see Andersen & Chen, 2002), a process that is assumed to serve
meaning-making functions (Glassman & Andersen, 1999b). Five studies tested the
more specific notion that implicit activation of an SO representation in
transference should indirectly activate the worldview shared with the SO, leading
to its active pursuit, validation, and protection. Shared worldviews were
assessed beforehand, both idiographically, as values (Studies 1 and 4), and
nomothetically, as political ideology or religious beliefs (Studies 2, 3, and 5).
In each experiment, participants learned about new persons, one subtly resembling
their own SO. Transference was assessed (memory bias; positive evaluation; see
Andersen, Reznik, & Manzella, 1996) and, crucially, as predicted, when
considering the new person resembling their SO (vs. the control persons),
participants showed faster response latencies in a lexical decision task to words
reflecting the worldview shared with the SO (vs. held only personally, Studies 1
3, or only by the SO, Study 3). With this person, they also anticipated a more
meaningful interaction and actively socially tuned to the SO-shared worldview,
selecting conversation topics reflecting the SO-shared worldview (vs. personally
held or SO-held topics, Studies 1-3). Finally, threatening the SO-shared
worldview with this person (vs. threatening personally held, SO-held, or
irrelevant worldviews) prompted goal activation to restore the disrupted meaning
(Studies 4 and 5), assessed by response latency in a lexical decision task.
Transference thus evokes shared meaning systems and serves epistemic functions.
PMID- 26414845
TI - The atomic-scale nucleation mechanism of NiTi metallic glasses upon isothermal
annealing studied via molecular dynamics simulations.
AB - Nucleation is one of the most essential transformation paths in phase transition
and exerts a significant influence on the crystallization process. Molecular
dynamics simulations were performed to investigate the atomic-scale nucleation
mechanisms of NiTi metallic glasses upon devitrification at various temperatures
(700 K, 750 K, 800 K, and 850 K). Our simulations reveal that at 700 K and 750 K,
nucleation is polynuclear with high nucleation density, while at 800 K it is
mononuclear. The underlying nucleation mechanisms have been clarified,
manifesting that nucleation can be induced either by the initial ordered clusters
(IOCs) or by the other precursors of nuclei evolved directly from the supercooled
liquid. IOCs and other precursors stem from the thermal fluctuations of bond
orientational order in supercooled liquids during the quenching process and
during the annealing process, respectively. The simulation results not only
elucidate the underlying nucleation mechanisms varied with temperature, but also
unveil the origin of nucleation. These discoveries offer new insights into the
devitrification mechanism of metallic glasses.
PMID- 26414846
TI - The Evolving HIV-1 Epidemic in Warao Amerindians Is Dominated by an Extremely
High Frequency of CXCR4-Utilizing Strains.
AB - We previously reported a high prevalence of HIV-1 infection in Warao Amerindians
from Venezuela due to the rapid spread of a single B subtype strain. In this
study we evaluated the coreceptor use of the HIV-1 strains infecting this
Amerindian community. Sequences of the HIV-1 V3 loop from 56 plasma samples were
genotyped for coreceptor use. An extremely high frequency of CXCR4 strains was
found among HIV-1-infecting Waraos (47/49, 96%), compared to HIV-1 strains
infecting the non-Amerindian Venezuelan population (35/79, 44%, p < 0.00001).
Evolutionary analysis showed that a significant number of infections occurred
between 1 and 12 months before collection and that a great proportion (50-70%) of
HIV-1 transmissions occurred within the very early phase of infection (<=12
months). This is consistent with an initial infection dominated by an X4 strain
or a very rapid selection of X4 variants after infection. This Amerindian
population also exhibits the highest prevalence of tuberculosis in Venezuela,
being synergistically bad prognostic factors for the evolution of morbidity and
mortality in this vulnerable population.
PMID- 26414847
TI - Robot-Assisted Laparoscopic Donor Nephrectomy vs Standard Laparoscopic Donor
Nephrectomy: A Prospective Randomized Comparative Study.
AB - OBJECTIVE: The goal of this randomized controlled trial was to compare the
outcomes of robot-assisted laparoscopic donor nephrectomy (RDN) with standard
laparoscopic donor nephrectomy (LDN). MATERIALS AND METHODS: Forty-five voluntary
kidney donors (27 for right subgroup and 18 for left subgroup) who met inclusion
and exclusion criteria were randomized into 2 groups, RDN and LDN in 1:2 ratio.
Primary endpoints were visual analogue scale (VAS) pain scores, analgesic
requirement, and hospital stay of donors. Secondary endpoints were donor's
intraoperative and postoperative parameters, graft outcomes, and donor surgeon's
difficulty scores. RESULTS: All procedures were completed without any
intraoperative complications. VAS pain scores at 6, 24, and 48 hours (p = 0.00),
analgesic requirement (p = 0.00), and hospital stay (p = 0.00) were less in RDN
than in LDN. Longer graft arterial length could be preserved with robotic
approach on right side (p = 0.03) but not on left side (p = 0.77). The RDN group
required more number of ports (p = 0.00), longer retrieval time (p = 0.00), and
warm ischemia time (WIT) (p = 0.01). Total operative time (p = 0.14), hemoglobin
drop (p = 0.97), postoperative donor complications (p = 0.97), and the recipient
estimated glomerular filtration rate at 9 months (p = 0.64) were similar in both
groups. Difficulty scores of console surgeon were less in most steps on right
side but not on left side. Patient-side surgeon in RDN had higher difficulty
scores for retrieval. CONCLUSION: RDN is safe and is associated with better
morbidity profile than LDN. Robotic approach provides technical ease and
facilitates preservation of longer length of renal artery on right side. Left RDN
is associated with longer WIT; however, this does not translate into poor graft
outcome.
PMID- 26414848
TI - Identification of a New Type of Covalent PPARgamma Agonist using a Ligand-Linking
Strategy.
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
activated transcription factor that plays an important role in adipogenesis and
glucose metabolism. The ligand-binding pocket (LBP) of PPARgamma has a large Y
shaped cavity with multiple subpockets where multiple ligands can simultaneously
bind and cooperatively activate PPARgamma. Focusing on this unique property of
the PPARgamma LBP, we describe a novel two-step cell-based strategy to develop
PPARgamma ligands. First, a combination of ligands that cooperatively activates
PPARgamma was identified using a luciferase reporter assay. Second, hybrid
ligands were designed and synthesized. For proof of concept, we focused on
covalent agonists, which activate PPARgamma through a unique activation mechanism
regulated by a covalent linkage with the Cys285 residue in the PPARgamma LBP.
Despite their biological significance and pharmacological potential, few covalent
PPARgamma agonists are known except for endogenous fatty acid metabolites. With
our strategy, we determined that plant-derived cinnamic acid derivatives
cooperatively activated PPARgamma by combining with GW9662, an irreversible
antagonist. GW9662 covalently reacts with the Cys285 residue. A docking study
predicted that a cinnamic acid derivative can bind to the open cavity in GW9662
bound PPARgamma LBP. On the basis of the putative binding mode, structures of
both ligands were linked successfully to create a potent PPARgamma agonist, which
enhanced the transactivation potential of PPARgamma at submicromolar levels
through covalent modification of Cys285. Our approach could lead to the discovery
of novel high-potency PPARgamma agonists.
PMID- 26414849
TI - Spontaneous lesions in endocrine glands of experimental Wistar rats and beagle
dogs.
AB - A retrospective analysis was undertaken at Zydus Research Centre to understand
the incidences of spontaneous lesions in endocrine glands of Wistar rats and
beagle dogs. The data from a total of 841 Wistar rats (418 males and 423 females)
and 144 beagle dogs (72 males and 72 females) was used from placebo/vehicle
treated control group of different non-clinical toxicity studies. The lesions in
various endocrine glands were classified according to the species and age of the
animals at termination of study. Among the endocrine glands, the highest numbers
(types) of spontaneous lesions were observed in adrenal glands followed in
descending order by pituitary, thyroid, endocrine pancreas and parathyroid glands
in Wistar rats. In beagle dogs, highest numbers (types) of spontaneous lesions
were seen in adrenals followed by thyroid, endocrine pancreas, pituitary and
parathyroid gland. In adrenal glands of Wistar rats, the incidences of cortical
cell vacuolation, hemorrhages and hemangiectasis/peliosis were increased with
age. Incidence of peliosis at ~110 weeks of age was higher in female rats. Among
the proliferative lesions in rats, higher incidences of cortical cell hyperplasia
was observed followed by medullary hyperplasia, complex pheochromocytoma,
cortical cell adenoma and cortical adenocarcinoma. In beagle dogs, the incidences
of hemangiectasis and cortical cell vacuolation in adrenal glands were higher in
18-21 months aged dogs in both the sexes as compared to 10-12 months of age. In
pituitary gland, the incidences of cystic changes were higher in older rats and
dogs and the incidences were more in beagles as compared to rats. In thyroid
glands, C-cell (parafollicular cells) hyperplasia/complex was observed more
frequently in both the species. Few incidences of cystic changes were observed in
parathyroid of 18-21 months aged beagle dogs. In endocrine pancreas, few
incidences of islet-cell vacuolation, atrophy and hyperplasia were observed in
both the species. The Islet cell hyperplasia was found to be more frequent in
male rats at ~110 weeks of age.
PMID- 26414850
TI - Regional contribution to PM1 pollution during winter haze in Yangtze River Delta,
China.
AB - To quantify regional sources contributing to submicron particulate matter (PM1)
pollution in haze episodes, on-line measurements combining two modeling methods,
namely, positive matrix factorization (PMF) and backward Lagrangian particle
dispersion modeling (LPDM), were conducted for the period of one month in urban
Nanjing, a city located in the western part of Yangtze River Delta (YRD) region
of China. Several multi-day haze episodes were observed in December 2013. Long
range transport of biomass burning from the southwestern YRD region largely
contributed to PM1 pollution with more than 25% of total organics mass in a
lasting heavy haze. The LPDM analysis indicates that regional transport is a main
source contributing to secondary low-volatility production. The high-potential
source regions of secondary low-volatility production are mainly located in areas
to the northeast of the city. High aerosol pollution was mainly contributed by
regional transport associated with northeastern air masses. Such regional
transport on average accounts for 46% of total NR-PM1 with sulfate and aged low
volatility organics being the largest fractions (>65%).
PMID- 26414851
TI - Implementing constrained multi-time approach with bootstrap analysis in ME-2: An
application to PM2.5 data from Florence (Italy).
AB - Advanced receptor models have been recently developed and tested in order to
improve the resolution of apportionment problems reducing rotational ambiguity of
results and aiming at identifying a larger number of sources. In particular,
multi-time model is a factor analysis method able to compute source profiles and
contributions using aerosol compositional data with different time resolutions.
Unlike traditional factor analysis, each measured value can be inserted into
multi-time model with its original time schedule, thus all temporal information
can be effectively used in the modelling process. In this work, multi-time model
was expanded in order to impose constraints on modelled factors aiming at
improving the source identification. Moreover, as far as we know for the first
time, a suitable bootstrap technique was implemented in the multi-time scheme to
estimate the uncertainty of the final constrained solutions. These implemented
approaches were tested on a PM2.5 (particulate matter with aerodynamic diameter
<2.5 MUm) dataset composed of 24-h samples collected during one year and hourly
data sampled in parallel for two shorter periods in Florence (Italy). The daily
samples were chemically characterised for elements, ions and carbonaceous
components while elemental concentrations only were available for high-time
resolved samples. The application of the advanced model revealed the major
contribution from traffic (accounting for 37% of PM2.5 as annual average) and
allowed an accurate characterisation of involved emission processes. In
particular, exhaust and non-exhaust emissions were identified. The constraints
imposed in the continuation run led to a better description of the factor
associated to nitrates and also of biomass burning profile and the bootstrap
results gave useful information to assess the reliability of source apportionment
solutions. Finally, the comparison with the results computed by ME-2 base model
applied to daily and hourly compositional data separately demonstrated the
advantages provided by the multi-time approach.
PMID- 26414852
TI - Commentary: Mapping the Human Exposome: Without It, How Can We Find Environmental
Risk Factors for ALS?
PMID- 26414853
TI - Occupational Exposure to Electric Shocks and Magnetic Fields and Amyotrophic
Lateral Sclerosis in Sweden.
AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) has been consistently related to
"electric occupations," but associations with magnetic field levels were
generally weaker than those with electrical occupations. Exposure to electric
shock has been suggested as a possible explanation. Furthermore, studies were
generally based on mortality or prevalence of ALS, and studies often had limited
statistical power. METHODS: Using two electric shock and three magnetic field job
exposure matrices, we evaluated the relationship of occupational magnetic fields,
electric shocks, electric occupations, and incident ALS in a large population
based nested case-control study in Sweden. Subanalyses, specified a priori, were
performed for subjects by gender and by age (less than and more than 65 years).
RESULTS: Overall, we did not observe any associations between occupational
magnetic field or electric shock exposure and ALS. For individuals less than 65
years old, high electric shock exposure was associated with an odds ratio (OR) of
1.22 (95% confidence interval [CI] = 1.03, 1.43). The corresponding result for
the age group 65 years or older was OR = 0.92 (95% CI = 0.81, 1.05). Results were
similar regardless which job exposure matrices, exposure definitions, or
cutpoints were used. For electric occupations, ORs were close to unity,
regardless of age. For welders, no association was observed overall, although for
welders <65 years the OR was 1.52 (95% CI = 1.05, 2.21). CONCLUSIONS: In this
very large population-based study based on incident ALS case subjects, we did not
confirm previous observations of higher risk of ALS in electrical occupations,
and provided only weak support for associations between electric shocks and ALS.
PMID- 26414854
TI - Military Service and Amyotrophic Lateral Sclerosis in a Population-based Cohort.
AB - BACKGROUND: Military service has been suggested to be associated with an
increased risk of amyotrophic lateral sclerosis (ALS), but only one prospective
study-of a volunteer cohort-has examined this question. METHODS: We prospectively
assessed the relation between service in the military and ALS mortality among
participants in the National Longitudinal Mortality Study, a population
representative cohort of U.S. men and women surveyed from 1973 through 2002.
Participant follow-up was conducted from 1979 through 2002 for ALS mortality.
There were 696,743 men and 392,571 women who were 25 years old or more with
military service data. In this group, there were 375 male ALS deaths and 96
female ALS deaths. Adjusted hazard ratios (HRs) were calculated using Cox
proportional hazards. RESULTS: Men who served in the military had an increased
adjusted ALS death rate [HR: 1.23; 95% confidence interval (CI): 0.98, 1.53]
compared with those who did not serve. An increase in ALS mortality was found
among those who served during World War II (HR: 1.47; 95% CI: 1.13, 1.91) but not
during other time periods. This pattern of results was similar for women, but
with larger confidence intervals (HR for military service: 1.26; 95% CI: 0.29,
5.59; HR for service during World War II: 2.03; 95% CI: 0.45, 9.05). CONCLUSIONS:
Military personnel have an increased risk of ALS, which may be specific to
certain service periods although there was no data on actual deployment. Because
of the longer follow-up time for World War II veterans, we cannot rule out that
increased risk for those who served during other periods would be seen with
further follow-up.
PMID- 26414856
TI - Estimating the Impact of Health-related Behaviors on Geographic Variation in
Cardiovascular Mortality: A New Approach Based on the Synthesis of Ecological and
Individual-level Data.
AB - BACKGROUND: Incidence of and mortality from cardiovascular disease (CVD) exhibit
a strong geographical pattern, with inhabitants of more affluent neighborhoods
showing a substantially lower risk of CVD mortality than inhabitants of deprived
neighborhoods. Thus far, there is insufficient evidence as to what extent these
differences can be attributed to differences in health-related behaviors.
METHODS: Using a Hierarchical Related Regression approach, we combined individual
and aggregate (ecological) data to investigate the extent to which small-area
variation in CVD mortality in Dutch neighborhoods can be explained by several
behavioral risk factors (i.e., smoking, drinking, overweight, and physical
inactivity). The proposed approach combines the benefits of both an ecological
analysis (in terms of data availability and statistical power) and an individual
level analysis (in terms of identification of the parameters and interpretation
of the results). RESULTS: After correcting for differences in age and sex,
accounting for differences in the behavioral risk factors reduces income-related
inequalities in CVD mortality by approximately 30%. CONCLUSIONS: Direct targeting
of the excess prevalence of unhealthy behaviors in deprived neighborhoods is
identified as a relevant strategy to reduce inequalities in CVD mortality. Our
results also show that the proposed Hierarchical Related Regression approach
provides a powerful method for the investigation of small-area variation in
health outcomes.
PMID- 26414855
TI - Application of Latent Variable Methods to the Study of Cognitive Decline When
Tests Change over Time.
AB - BACKGROUND: The way a construct is measured can differ across cohort study
visits, complicating longitudinal comparisons. We demonstrated the use of factor
analysis to link differing cognitive test batteries over visits to common metrics
representing general cognitive performance, memory, executive functioning, and
language. METHODS: We used data from three visits (over 26 years) of the
Atherosclerosis Risk in Communities Neurocognitive Study (N = 14,252). We allowed
individual tests to contribute information differentially by race, an important
factor to consider in cognitive aging. Using generalized estimating equations, we
compared associations of diabetes with cognitive change using general and domain
specific factor scores versus averages of equally weighted standardized test
scores. RESULTS: Factor scores provided stronger associations with diabetes at
the expense of greater variability around estimates (e.g., for general cognitive
performance, -0.064 standard deviation units/year, standard error = 0.015, vs.
0.041 standard deviation units/year, standard error = 0.014), which is consistent
with the notion that factor scores more explicitly address error in measuring
assessed traits than averages of standardized tests. CONCLUSIONS: Factor analysis
facilitates use of all available data when measures change over time, and
further, it allows objective evaluation and correction for differential item
functioning.
PMID- 26414857
TI - A model-based reconstruction technique for quantitative myocardial perfusion
imaging.
AB - PURPOSE: To reduce saturation effects in the arterial input function (AIF)
estimation of quantitative myocardial first-pass saturation recovery perfusion
imaging by employing a model-based reconstruction. THEORY AND METHODS: Imaging
was performed with a saturation recovery prepared radial FLASH sequence. A model
based reconstruction was applied for reconstruction. By exploiting prior
knowledge about the relaxation process, an image series with different saturation
recovery times was reconstructed. By evaluating images with an effective
saturation time of approximately 3 ms, saturation effects in the AIF
determination were reduced. In a volunteer study, this approach was compared with
a standard prebolus technique. RESULTS: In comparison to the low-dose injection
of a prebolus acquisition, saturation effects were further reduced in the AIFs
determined using the model-based approach. These effects, which were clearly
visible for all six volunteers, were reflected in a statistically significant
difference of up to 20% in the absolute perfusion values. CONCLUSION: The
application of model-based reconstruction algorithms in quantitative myocardial
perfusion imaging promises a significant improvement of the AIF determination. In
addition to greatly reducing saturation effects that occur even for the prebolus
methods, only a single bolus has to be applied. Magn Reson Med 76:880-887, 2016.
(c) 2015 Wiley Periodicals, Inc.
PMID- 26414858
TI - Quantitative assessment of human and pet exposure to Salmonella associated with
dry pet foods.
AB - Recent Salmonella outbreaks associated with dry pet foods and treats highlight
the importance of these foods as previously overlooked exposure vehicles for both
pets and humans. In the last decade efforts have been made to raise the safety of
this class of products, for instance by upgrading production equipment, cleaning
protocols, and finished product testing. However, no comprehensive or
quantitative risk profile is available for pet foods, thus limiting the ability
to establish safety standards and assess the effectiveness of current and
proposed Salmonella control measures. This study sought to develop an ingredients
to-consumer quantitative microbial exposure assessment model to: 1) estimate pet
and human exposure to Salmonella via dry pet food, and 2) assess the impact of
industry and household-level mitigation strategies on exposure. Data on
prevalence and concentration of Salmonella in pet food ingredients, production
process parameters, bacterial ecology, and contact transfer in the household were
obtained through literature review, industry data, and targeted research. A
probabilistic Monte Carlo modeling framework was developed to simulate the
production process and basic household exposure routes. Under the range of
assumptions adopted in this model, human exposure due to handling pet food is
null to minimal if contamination occurs exclusively before extrusion. Exposure
increases considerably if recontamination occurs post-extrusion during coating
with fat, although mean ingested doses remain modest even at high fat
contamination levels, due to the low percent of fat in the finished product.
Exposure is highly variable, with the distribution of doses ingested by adult pet
owners spanning 3Log CFU per exposure event. Child exposure due to ingestion of
1g of pet food leads to significantly higher doses than adult doses associated
with handling the food. Recontamination after extrusion and coating, e.g., via
dust or equipment surfaces, may also lead to exposure due to the absence of
pathogen reduction steps after extrusion or at consumer households. Exposure is
potentially highest when Salmonella is transferred to human food that is left at
growth-promoting conditions. This model can be applied to evaluate the impact of
alternative Salmonella control measures during production, risk communication to
consumers, and regulatory standards.
PMID- 26414860
TI - Lupus Means Sacrifices: Perspectives of Adolescents and Young Adults With
Systemic Lupus Erythematosus.
AB - OBJECTIVE: Disease activity, organ damage, and treatment burden are often
substantial in children and adolescents with systemic lupus erythematous (SLE),
and the complex interplay among the developing child, parents, and peers makes
effective management difficult. We aimed to describe the experiences and
perspectives of adolescents and young adults diagnosed with juvenile-onset SLE to
inform strategies for improving treatment and health outcomes. METHODS: Focus
groups and face-to-face semistructured interviews were conducted with 26 patients
ages 14-26 years, from 5 Australian hospitals in 2013-2014. Focus groups and
interview transcripts were thematically analyzed. RESULTS: Five themes were
identified: marring identity (misrepresented self, heightened self-consciousness,
sense of isolation), restricting major life decisions (narrowed career options,
threat to parenthood), multifaceted confusion and uncertainty (frustration at
delayed diagnosis or misdiagnosis, needing age and culturally appropriate
information, ambiguity about cause of symptoms, prognostic uncertainty,
confronting transition to adult care), resentment of long-term treatment
(restricting ambition, animosity toward medication use), and gaining resilience
and coping capacities (desire for independence, developing self-reliance,
recalibrating perceived disease severity, depending on family and friends,
trusting physicians). CONCLUSION: Young patients with SLE perceive they have
substantially limited physical and social capacities and restricted personal and
career goals. Psychosocial and educational interventions targeted at improving
confidence, self-efficacy, disease-related knowledge, and social support, and at
resolving insecurities regarding patients' capacity for self-management may
alleviate psychosocial distress and improve adherence, and thus optimize health
outcomes of adolescents and young adults with SLE.
PMID- 26414859
TI - The Effects of the Endocannabinoids Anandamide and 2-Arachidonoylglycerol on
Human Osteoblast Proliferation and Differentiation.
AB - The endocannabinoid system is expressed in bone, although its role in the
regulation of bone growth is controversial. Many studies have examined the effect
of endocannabinoids directly on osteoclast function, but few have examined their
role in human osteoblast function, which was the aim of the present study. Human
osteoblasts were treated from seeding with increasing concentrations of
anandamide or 2-arachidonoylglycerol for between 1 and 21 days. Cell
proliferation (DNA content) and differentiation (alkaline phosphatase (ALP),
collagen and osteocalcin secretion and calcium deposition) were measured.
Anandamide and 2-arachidonoylglycerol significantly decreased osteoblast
proliferation after 4 days, associated with a concentration-dependent increase in
ALP. Inhibition of endocannabinoid degradation enzymes to increase
endocannabinoid tone resulted in similar increases in ALP production. 2
arachidonoylglycerol also decreased osteocalcin secretion. After prolonged (21
day) treatment with 2-arachidonoylglycerol, there was a decrease in collagen
content, but no change in calcium deposition. Anandamide did not affect collagen
or osteocalcin, but reduced calcium deposition. Anandamide increased levels of
phosphorylated CREB, ERK 1/2 and JNK, while 2-arachidonoylglycerol increased
phosphorylated CREB and Akt. RT-PCR demonstrated the expression of CB2 and TRPV1,
but not CB1 in HOBs. Anandamide-induced changes in HOB differentiation were CB1
and CB2-independent and partially reduced by TRPV1 antagonism, and reduced by
inhibition of ERK 1/2 and JNK. Our results have demonstrated a clear involvement
of anandamide and 2-arachidonoylglycerol in modulating the activity of human
osteoblasts, with anandamide increasing early cell differentiation and 2-AG
increasing early, but decreasing late osteoblast-specific markers of
differentiation.
PMID- 26414861
TI - Tick-borne encephalitis--lipid peroxidation and its consequences.
AB - BACKGROUND: The purpose of this study was to assess the processes of lipid
peroxidation with prostaglandin derivatives and reactive aldehydes being its
major indicators in cerebrospinal fluid (CSF), plasma and urine of patients with
tick-borne encephalitis (TBE). MATERIALS AND METHODS: This study included 60
patients with TBE and 56 healthy subjects. Lipid peroxidation was estimated by
the measurement of 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal (4-HHE),
malondialdehyde (MDA), acrolein, crotonaldehyde, and 4-oxononenal (4-ONE),
determined by GC-MS, F2-isoprostanes and neuroprostanes (NPs) level determined by
LC-MS. The level of 4-HNE-protein adducts was determined by ELISA. Phospholipase
A2 (PLA2), platelet-activating factor acetylhydrolase (PAF-AH) and glutathione
peroxidase (GSH-Px) activities and vitamin E level were determined
spectrophotometrically and by HPLC, respectively. In parallel, the plasma levels
of phospholipid acids such as arachidonic acid (AA), linoleic acid (LA) and
docosahexaenoic acid (DHA) were monitored. RESULTS: A significant decrease in AA,
LA, DHA level and GSH-Px activity (by about 20, 69, 11 and 18%, respectively) was
observed. The consequence of enhanced phospholipid peroxidation was almost 7
times higher plasma level of F2-isoprostanes and 3-fold increase in NPs level in
CSF of TBE patients. Additionally a 3.5-fold increase in the CSF level of MDA, 5
fold increase in the plasma level of 4-HNE and urine level of 4-HHE in TBE
patients was observed. Decreased plasma activity of PLA2 with an increase in the
PAF-AH activity was observed. CONCLUSION: Lipid peroxidation occurring during TBE
development indicates its relevance in pathophysiology of this disease. Moreover
lipid peroxidation products might be useful for the diagnosis of TBE.
PMID- 26414862
TI - Investigational new drugs for the treatment of acute coronary syndrome.
AB - INTRODUCTION: Ischemic heart disease is the most common cause of death worldwide.
Despite improvements in interventional and pharmacological therapy for acute
coronary syndrome (ACS), the risk of recurrent myocardial ischemia and mortality
early after ACS remains high. Our improved understanding of the increasing role
of inflammation in the pathogenesis of ACS and its relationship to
atherosclerotic plaque rupture and thrombosis has led to the development of more
potent anti-thrombotic and novel anti-inflammatory therapies for the treatment of
ACS. AREAS COVERED: In this review, the authors explore: the developing
pharmacotherapy in the field of cardiology for ACS; antiplatelet agents (both
further development of classical modalities together with pioneering agents);
evolving use of anticoagulation in its treatment, and exploration in the use of
novel anti-inflammatories and biological agents. EXPERT OPINION: Data from trials
involving the use of immunological and cellular-based treatments show promising
results and herald further possible reduction in infarct burden in ACS alongside
the possibility of recovery in cardiac function following infarction.
PMID- 26414863
TI - In Vivo Anastomosis and Perfusion of a Three-Dimensionally-Printed Construct
Containing Microchannel Networks.
AB - The field of tissue engineering has advanced the development of increasingly
biocompatible materials to mimic the extracellular matrix of vascularized tissue.
However, a majority of studies instead rely on a multiday inosculation between
engineered vessels and host vasculature rather than the direct connection of
engineered microvascular networks with host vasculature. We have previously
demonstrated that the rapid casting of three-dimensionally-printed (3D)
sacrificial carbohydrate glass is an expeditious and a reliable method of
creating scaffolds with 3D microvessel networks. Here, we describe a new surgical
technique to directly connect host femoral arteries to patterned microvessel
networks. Vessel networks were connected in vivo in a rat femoral artery graft
model. We utilized laser Doppler imaging to monitor hind limb ischemia for
several hours after implantation and thus measured the vascular patency of
implants that were anastomosed to the femoral artery. This study may provide a
method to overcome the challenge of rapid oxygen and nutrient delivery to
engineered vascularized tissues implanted in vivo.
PMID- 26414864
TI - Effects of waterborne fluoxetine on stress response and osmoregulation in
zebrafish.
AB - The presence of fluoxetine in aquatic environments has been reported for decades.
Here, we investigate the effects of exposure to fluoxetine on the stress response
and osmoregulation in zebrafish. We show that stress response alters
osmoregulation and that fluoxetine inhibits these stress-related changes in
osmoregulation. The results suggest that the presence of fluoxetine in aquatic
ecosystems can cause changes in response to stress and osmoregulation in fish.
PMID- 26414865
TI - Motor Readiness Increases Brain Connectivity Between Default-Mode Network and
Motor Cortex: Impact on Sampling Resting Periods from fMRI Event-Related Studies.
AB - The default-mode network (DMN) has been implicated in many conditions. One
particular function relates to its role in motor preparation. However, the
possibly complex relationship between DMN activity and motor preparation has not
been fully explored. Dynamic interactions between default mode and motor networks
may compromise the ability to evaluate intrinsic connectivity using resting
period data extracted from task-based experiments. In this study, we investigated
alterations in connectivity between the DMN and the motor network that are
associated with motor readiness during the intervals between motor task trials.
fMRI data from 20 normal subjects were acquired under three conditions: pure
resting state; resting state interleaved with brief, cued right-hand movements at
constant intervals (lower readiness); and resting state interleaved with the same
movements at unpredictable intervals (higher readiness). The functional
connectivity between regions of motor and DMNs was assessed separately for
movement periods and intertask intervals. We found a negative relationship
between the DMN and the left sensorimotor cortex during the task periods for both
motor conditions. Furthermore, during the intertask intervals of the
unpredictable condition, the DMN showed a positive relationship with right
sensorimotor cortex and a negative relation with the left sensorimotor cortex.
These findings indicate a specific modulation on motor processing according to
the state of motor readiness. Therefore, connectivity studies using task-based
fMRI to probe DMN should consider the influence of motor system modulation when
interpreting the results.
PMID- 26414866
TI - Differential protein expression and oncogenic gene network link tyrosine kinase
ephrin B4 receptor to aggressive gastric and gastroesophageal junction cancers.
AB - Transmembrane tyrosine-kinase Ephrin receptors promote tumor progression and/or
metastasis of several malignancies including leukemia, follicular lymphoma,
glioma, malignant pleural mesothelioma, papillary thyroid carcinoma, sarcomas and
ovarian, breast, bladder and non-small cell lung cancers. They also drive
intestinal stem cell proliferation and positioning, control intestinal tissue
boundaries and are involved in liver, pancreatic and colorectal cancers,
indicating involvement in additional digestive system malignancies. We
investigated the role of Ephrin-B4 receptor (EPHB4), and its ligand EFNB2, in
gastric and gastroesophageal junction cancers in patient cohorts through
computational, mathematical, molecular and immunohistochemical analyses. We show
that EPHB4 is upregulated in preneoplastic gastroesophageal lesions and its
expression further increased in gastroesophageal cancers in several independent
cohorts. The closely related EPHB6 receptor, which also binds EFNB2, was
downregulated in all tested cohorts, consistent with its tumor-suppressive
properties in other cancers. EFNB2 expression is induced in esophageal cells by
acidity, suggesting that gastroesophageal reflux disease (GERD) may constitute an
early triggering event in activating EFNB2-EPHB4 signaling. Association of EPHB4
to both Barrett's esophagus and to advanced tumor stages, and its overexpression
at the tumor invasion front and vascular endothelial cells intimate the notion
that EPHB4 may be associated with multiple steps of gastroesophageal
tumorigenesis. Analysis of oncogenomic signatures uncovered the first EPHB4
associated gene network (false discovery rate: 7 * 10(-90) ) composed of a five
transcription factor interconnected gene network that drives proliferation,
angiogenesis and invasiveness. The EPHB4 oncogenomic network provides a molecular
basis for its role in tumor progression and points to EPHB4 as a potential tumor
aggressiveness biomarker and drug target in gastroesophageal cancers.
PMID- 26414867
TI - Chronic alpha-Tocopherol Increases Central Monoamines Synthesis and Improves
Cognitive and Motor Abilities in Old Rats.
AB - Limiting enzymes in the synthesis of brain monoamines seems to be susceptible to
oxidative damage, one of the most important factors in aging. It has been
suggested that the use of anti-oxidants can reduce the rate of free radical
production related with aging and the associated damage. Therefore, this study
aims to analyze the effects of the chronic treatments with the anti-oxidant alpha
tocopherol (vitamin E) on central monoamines (high-performance liquid
chromatography [HPLC] analysis) mediating cognitive functions, as well as on the
evaluation of memory and motor abilities in old rats measured by radial maze,
Barnes maze, novel object recognition test, and rotarod test. Results show that
alpha-tocopherol significantly increased in a dose- and/or time-dependent manner
the synthesis rate and the levels of monoaminergic neurotransmitters (serotonin,
dopamine, and noradrenaline) in the hippocampus and striatum, brain regions
involved in memory processing and motor coordination. These positive
neurochemical effects, largely due to an increased activity of the limiting
enzymes in monoamines synthesis, tryptophan hydroxylase and tyrosine hydroxylase,
were accompanied by an improvement in cognitive and motor abilities in old rats.
Altogether these findings suggest that alpha-tocopherol exhibits neuroprotective
actions in old rats; thus, diets with alpha-tocopherol might represent a
promising strategy to mitigate or delay the cognitive and motor decline associate
with aging and related-diseases.
PMID- 26414868
TI - Comparing symptomatic and functional outcomes over 5 years in two nonclinical
cohorts characterized by binge eating with and without objectively large
episodes.
AB - OBJECTIVE: The aim was to compare symptomatic and functional outcomes over 5
years in women with regular subjective (SBEs), objective (OBEs), and no regular
binge eating episodes. METHOD: Data were derived from two cohorts of 330 women
with high levels of eating disorders symptoms followed over 5 years. Three groups
were formed: (a) regular SBEs but no regular OBEs (N = 68), (b) regular OBEs with
or without regular SBEs (N = 154), and (c) with no regular binge eating episodes
(N = 108). RESULTS: At baseline, the groups did not differ significantly in
restraint scores and quality of life. People in the OBE group scored higher than
those in the SBE group in body mass index (BMI). Those who had no regular binge
eating had lower global Eating Disorder Examination Questionnaire (EDE-Q) and
weight and shape concern scores than those with regular SBEs, and lower eating
concern scores than either binge eating groups. Across the follow-up, there were
no significant effects of being in either binge eating or the nonbinge eating
group on the rates of change in BMI, general psychological distress, quality of
life, or EDE-Q scores with the exception that OBE group had a significantly
different rate of change in eating concern and psychological distress compared to
the group without regular binge eating. DISCUSSION: Individuals that report
regular SBEs without regular OBEs represent a group with similar mental hardship
and outcomes to those with regular OBEs. The findings support inclusion of
regular SBEs in criteria for eating disorder diagnostic categories characterized
by recurrent binge eating.
PMID- 26414869
TI - Melatonin for Spinal Cord Injury in Animal Models: A Systematic Review and
Network Meta-Analysis.
AB - Spinal cord injury (SCI) leads to loss of function below the lesion and affects
individuals worldwide. An increasing number of experimental studies support the
effectiveness of melatonin (MT) for SCI. Our objectives were to investigate
neurological recovery and anti-oxidant effects of MT in animal models of SCI, and
to explore the appropriate dose. Published MT studies in SCI animal models
described in six databases were searched. Two practiced investigators selected
the studies, extracted the data, and independently evaluated the quality of the
included studies. A meta-analysis evaluated the effect of MT in SCI and a network
meta-analysis was performed to explore the appropriate MT dose for SCI models.
Thirteen studies were analyzed, of which three were high quality. The results of
the meta-analysis manifested that the behavioral evaluation (Basso, Beattie, and
Bresnahan scales, n = 90, p = 0.003; motor function scores, n = 92, p = 0.004;
Tarlov's criteria, n = 150, p = 0.002; inclined plane test, n = 150, p = 0.001)
and biochemical outcomes (malondialdehyde, n = 121, p = 0.0010; glutathione
levels, n = 64, p < 0.0001; and myeloperoxidase activity, n = 32, p < 0.00001)
were improved, compared with the control group, after MT administration. A dose
of 12.5 mg/kg was most effective in SCI rat models. Studies indicated that MT
administration significantly improved neurological recuperation and anti-oxidant
effects in rat models of SCI. The appropriate dose of MT was 12.5 mg/kg for SCI
rat models. The majority of included studies were low quality; however, optimal
MT treatment in SCI still requires high quality studies.
PMID- 26414870
TI - Work with men to end violence against women: a critical stocktake.
AB - This paper provides a critical assessment of efforts to involve men in the
prevention of men's violence against women. Although there is a substantial
evidence base attesting to the effectiveness of at least some strategies and
interventions, this field is also limited in important ways. Violence prevention
efforts often have focused on changing men's attitudes, rather than also seeking
to transform structural and institutional inequalities. While feminist and queer
scholarship has explored diversities and pluralities in the organisation of
sexuality, much violence prevention work often assumes a homogenously
heterosexual male constituency. Too often this work is conceptually simplistic
with regard to gender. Against this background, this paper contests and
complicates several assumptions that are part of an emerging consensus in men's
violence prevention: first, that it is in men's interests to support progress
towards non-violence and gender equality; second, that the best people to engage
and work with men are other men; and finally, the strengths and limitations of
inviting and drawing on 'real men'. A critical assessment of the field's working
assumptions is vital if it is to contribute to the future prevention of men's
violence against women.
PMID- 26414871
TI - Ultrasound-Guided Approach for L5 Dorsal Ramus Block and Fluoroscopic Evaluation
in Unpreselected Cadavers.
AB - BACKGROUND AND OBJECTIVES: Medial branch blocks are frequently performed to
diagnose lumbar facet-joint-mediated pain. Ultrasound guidance can increase
practicability and eliminate exposure to ionizing radiation when compared with
fluoroscopy. However, ultrasound-guided L5 dorsal ramus block, which, together
with L4 medial branch block is necessary to anesthetize the most commonly
affected facet joint L5/S1, has not been described so far. The objective of this
study was to develop a technique and to evaluate its accuracy with standard
fluoroscopy in unpreselected cadavers. METHODS: Twenty ultrasound-guided L5
dorsal ramus block approaches were performed with a new oblique out-of-plane
technique in a rotated cross-axis view bilaterally in 10 cadavers. After checking
the needle position in a second perpendicular sonographic plane, the final needle
position was confirmed with conventional fluoroscopy by an independent observer.
RESULTS: All cadavers had significant degenerations of the lumbar spine, and 5 of
them had moderate to severe spondylolisthesis. Skin-to-target distances were 42
+/-7 mm. Sixteen L5 dorsal ramus block attempts were located at the exact
radiological target, 1 was slightly too lateral, and 3 were slightly too caudal
(3-10 mm away). The overall success rate in unpreselected cadavers reached 80%
(95% confidence interval, 56%-94%) and in the subgroup of corpses without
spondylolisthesis 100% (95% confidence interval, 69%-100%). CONCLUSIONS: This is
the first study to show that ultrasound-guided L5 dorsal ramus block is accurate
and feasible in the absence of significant spondylolisthesis when performed with
an oblique out-of-plane technique.
PMID- 26414872
TI - IL-13 Inhibits Multicilin Expression and Ciliogenesis via Janus Kinase/Signal
Transducer and Activator of Transcription Independently of Notch Cleavage.
AB - Loss of ciliated cells and increases in goblet cells are seen in respiratory
diseases such as asthma. These changes result in part from reduced
differentiation of basal progenitor cells to ciliated cells during injury and
repair. The T helper 2 cytokine, IL-13, has been shown to inhibit ciliated cell
differentiation, but the mechanism is not clearly understood. We recently showed
that Notch signaling inhibits ciliated cell differentiation in submerged culture
by repressing multicilin and forkhead box J1 (FOXJ1) expression, genes required
for ciliogenesis. Using a novel method to study ciliated cell differentiation, we
investigated the relationship between IL-13 and Notch signaling pathways. We
found that IL-13 inhibits ciliated cell differentiation by repressing multicilin
and FOXJ1 expression but does so independent of Notch signaling. In addition, we
show that pharmacological inhibition of Janus kinase/signal transducer and
activator of transcription, but not mitogen activated protein kinase kinase,
signaling rescues multicilin and FOXJ1 expression and ciliated cell
differentiation in the presence of IL-13. These findings indicate that regulation
of multicilin expression by two distinct signaling pathways affects ciliated cell
differentiation. In addition, the requirement for Janus kinase activation in IL
13-induced inhibition of ciliogenesis provides a potential therapeutic target for
the treatment of respiratory disease.
PMID- 26414874
TI - Effect of fusion status of sternum in stature estimation - A study from South
India.
AB - Forensic anthropologists examine and identify skeletal, dismembered and
commingled remains in a legal context to establish the biological profile of the
deceased. Stature estimation is one of the important parameters in establishing
the biological profile. The present study is planned to derive regression models
for stature estimation from sternal measurements. Various factors are likely to
affect stature estimation in forensic investigations. Since, none of the previous
researchers have studied the effect of fusion status on stature estimation from
sternum and its segments, the present study attempts to find if the fusion status
of the sternum affect its reliability and accuracy in stature estimation. The
sample of the present study consisted of 117 sterna that were obtained from
autopsied bodies. Five measurements i.e. Length of manubrium (M), length of
mesosternum (B), combined length of manusbrium and mesosternum and the (M + B),
width at first sternabrae (S1) and width of 3rd sternabrae (S3) were taken on the
autopsied sterna. The sterna were classified as fused (both manubriosternal and
xiphisternal joints were fused), partly fused (only one of the manubriosternal or
xiphisternal joints was fused) and not fused (both manubriosternal and
xiphisternal joints were not fused). Regression models were derived using
statistical methods. All the sternal measurements show a positive however, a weak
correlation with stature. Thus, it can be concluded that the accuracy and
reliability of stature estimation from sternum and its segments is quite low in
practical situations. Among the sterna classified based on the fusion status, the
length measurements of completely fused sterna show significant correlation with
the stature. None of the other sternal measurements on the non-fused or partly
fused sterna show statistically significant correlation with stature. The present
study concludes that the fusion status of the sternum is likely to affect the
reliability and accuracy in estimation of stature. The findings of this study
however, should be considered 'preliminary' until they are corroborated by
similar studies based on larger samples from different populations.
PMID- 26414873
TI - Mesenchymal Stem Cells Within Gelatin/CaSO4 Scaffolds Treated Ex Vivo with Low
Doses of BMP-2 and Wnt3a Increase Bone Regeneration.
AB - The delivery of osteogenic factors is a proven therapeutic strategy to promote
bone regeneration. Bone morphogenetic proteins (BMPs) constitute a family of
cytokines with well-known osteogenic and bone regenerative abilities. However,
clinical uses of BMPs require high doses that have been associated with
complications such as osteolysis, ectopic bone formation, or hematoma formation.
In the present work, we sought to improve bone tissue engineering through an
approach that combines the use of bone marrow-derived mesenchymal stem cells
(BMMSCs), composite scaffolds, and osteoinductive agents. We employed a composite
gelatin/CaSO4 scaffold that allows for an early expansion of seeded BMMSCs, which
is followed by an increased level of osteogenic differentiation after 10 days in
culture. Furthermore, this scaffold enhanced bone formation by BMMSCs in a mouse
model of critical-sized calvarial defect. More importantly, our results
demonstrate that ex vivo pretreatment of BMMSCs with low amounts of BMP-2 (2 nM)
and Wnt3a (50 ng/mL) for 24 h cooperatively increases the expression of
osteogenic markers in vitro and bone regeneration in the critical-sized calvarial
defect mouse model. These data provide a strong rationale for the development of
an ex vivo cooperative use of BMP-2 and Wnt3a. Osteogenic factor cooperation
might be applied to reduce the required amount of growth factors while obtaining
higher therapeutic effects.
PMID- 26414875
TI - Sexual dimorphism in foot length ratios among North Indian adolescents.
AB - Determination of sex along with other parameters of identification like stature,
age and ancestry is one of the foremost criteria in establishing the biological
profile of an individual. The present study was conducted to analyze the sex
differences in the foot length ratios in a North Indian adolescent population.
The study was conducted on 149 females and 154 males aged from 13 to 18 years.
Foot length measurements were taken from pternion to the most anterior part of
each toe and designated as T1, T2, T3, T4, and T5 respectively for first to fifth
toes on both the feet in each participant using standard methods and techniques.
A total of ten ratios (T1:T2, T1:T3, T1:T4, T1:T5, T2:T3, T2:T4, T2:T5, T3:T4,
T3:T5, and T4:T5) were thus, obtained and the same were analyzed for sex
differences using Student's t-test. Stature was measured in each participant and
Pearson's correlation coefficients were calculated to find the correlation
between various foot length ratios, age and stature. Receiver Operating
Characteristic (ROC) curve was employed to test the sexing accuracy of the
variables. P-value of less than 0.05 was considered as statistically significant.
Foot length dimensions from each toe (T1 to T5) and stature were found to be
significantly higher in males than females. The foot length ratios did not show
any statistically significant correlation with stature. Statistically significant
sex differences were exhibited by ratios between T1 and T2 (p = 0.002), T1 and T3
(p = 0.001), T1 and T4 (p < 0.001), T1 and T5 (p = 0.001), and T2 and T4 (p =
0.014). Maximum sex differences were evident for foot length ratio between T1 and
T4 (63.4%), and minimum for the ratio between T2 and T4 (56.5%). Though foot
length measurements are significantly larger in males, its utility in sex
differentiation may be limited owing to its direct correlation with stature of an
individual. It has been observed that the foot length ratios are independent of
stature and thus, can be considered a better sex determinant since they are not
influenced by the body built of an individual. Apart from ratio between T2 and
T4, only the foot length ratios with reference to first toe (T1:T2, T1:T3, T1:T4,
T1:T5) were found to exhibit significant sex-differences. The present research
concludes that the foot length ratios exhibit sex differences in the study
population. However, its utility in forensic investigations may be limited owing
to the lower sexing accuracy of foot length ratios.
PMID- 26414876
TI - Retention, erosion, and loss of the carotenoid biosynthetic pathway in the
nonphotosynthetic green algal genus Polytomella.
PMID- 26414878
TI - Sialic Acid-Imprinted Fluorescent Core-Shell Particles for Selective Labeling of
Cell Surface Glycans.
AB - The expression of cell surface glycans terminating with sialic acid (SA) residues
has been found to correlate with various disease states there among cancer. We
here report a novel strategy for specific fluorescence labeling of such motifs.
This is based on sialic acid-imprinted core-shell nanoparticles equipped with
nitrobenzoxadiazole (NBD) fluorescent reporter groups allowing environmentally
sensitive fluorescence detection at convenient excitation and emission
wavelengths. Imprinting was achieved exploiting a hybrid approach combining
reversible boronate ester formation between p-vinylphenylboronic acid and SA, the
introduction of cationic amine functionalities, and the use of an NBD-appended
urea-monomer as a binary hydrogen-bond donor targeting the SA carboxylic acid and
OH functionalities. The monomers were grafted from 200 nm RAFT-modified silica
core particles using ethylene glycol dimethacrylate (EGDMA) as cross-linker
resulting in a shell thickness of ca. 10 nm. The particles displayed strong
affinity for SA in methanol/water mixtures (K = 6.6 * 10(5) M(-1) in 2% water,
5.9 * 10(3) M(-1) in 98% water, B(max) ~ 10 MUmol g(-1)), whereas binding of the
competitor glucuronic acid (GA) and other monosaccharides was considerably weaker
(K (GA) = 1.8 * 10(3) M(-1) in 98% water). In cell imaging experiments, the
particles selectively stained different cell lines in correlation with the SA
expression level. This was further verified by enzymatic cleavage of SA and by
staining using a FITC labeled SA selective lectin.
PMID- 26414879
TI - Delivery of antigen to nasal-associated lymphoid tissue microfold cells through
secretory IgA targeting local dendritic cells confers protective immunity.
AB - BACKGROUND: Transmission of mucosal pathogens relies on their ability to bind to
the surfaces of epithelial cells, to cross this thin barrier, and to gain access
to target cells and tissues, leading to systemic infection. This implies that
pathogen-specific immunity at mucosal sites is critical for the control of
infectious agents using these routes to enter the body. Although mucosal delivery
would ensure the best onset of protective immunity, most of the candidate
vaccines are administered through the parenteral route. OBJECTIVE: The present
study evaluates the feasibility of delivering the chemically bound p24gag
(referred to as p24 in the text) HIV antigen through secretory IgA (SIgA) in
nasal mucosae in mice. RESULTS: We show that SIgA interacts specifically with
mucosal microfold cells present in the nasal-associated lymphoid tissue. p24-SIgA
complexes are quickly taken up in the nasal cavity and selectively engulfed by
mucosal dendritic cell-specific intercellular adhesion molecule 3-grabbing
nonintegrin-positive dendritic cells. Nasal immunization with p24-SIgA elicits
both a strong humoral and cellular immune response against p24 at the systemic
and mucosal levels. This ensures effective protection against intranasal
challenge with recombinant vaccinia virus encoding p24. CONCLUSION: This study
represents the first example that underscores the remarkable potential of SIgA to
serve as a carrier for a protein antigen in a mucosal vaccine approach targeting
the nasal environment.
PMID- 26414877
TI - Engineering large animal models of human disease.
AB - The recent development of gene editing tools and methodology for use in livestock
enables the production of new animal disease models. These tools facilitate site
specific mutation of the genome, allowing animals carrying known human disease
mutations to be produced. In this review, we describe the various gene editing
tools and how they can be used for a range of large animal models of diseases.
This genomic technology is in its infancy but the expectation is that through the
use of gene editing tools we will see a dramatic increase in animal model
resources available for both the study of human disease and the translation of
this knowledge into the clinic. Comparative pathology will be central to the
productive use of these animal models and the successful translation of new
therapeutic strategies.
PMID- 26414880
TI - Acute and chronic systemic corticosteroid-related complications in patients with
severe asthma.
AB - BACKGROUND: Many patients with severe asthma require maintenance treatment with
systemic corticosteroids (SCSs) to control daily symptoms and prevent serious
acute exacerbations, but chronic SCS use is associated with complications.
OBJECTIVE: We sought to evaluate the risk of SCS-related complications by SCS
exposure and quantify the associated health care costs and resource use in
patients with severe asthma. METHODS: We performed a longitudinal, open-cohort,
observational study using health insurance claims data (1997-2013: Medicaid) from
Florida, Iowa, Kansas, Missouri, Mississippi, and New Jersey. Eligible patients
were 12 years old or older with 2 or more asthma diagnoses and had more than 6
months of continuous SCS use. An open-cohort approach was used to classify
patients' follow-up into low, medium, and high SCS exposure (<= 6, >6-12, and >12
mg/d, respectively). Multivariate generalized estimating equation models were
used to estimate the adjusted risk of SCS-related complications for patients with
medium and high exposure compared with patients with low exposure and quantify
the resulting health care resource use and costs. RESULTS: The study included
3628 patients (mean age, 57.6 years; 68% female). Patients with medium and high
SCS exposure had significantly higher risks of SCS-related complications,
including infections and cardiovascular, metabolic, psychiatric, ocular,
gastrointestinal, and bone-related complications (odds ratio, 1.23-2.12 by
complication; P < .05 for all but one) versus those with low (reference group)
SCS exposure. Medium and high SCS exposure were also associated with
significantly more emergency department visits (incidence rate ratios, 1.31 [P =
.0004] and 1.78 [P < .0001]) and inpatient visits (incidence rate ratios, 1.25 [P
< .0001] and 1.59 [P < .0001]) versus low SCS exposure. CONCLUSIONS: A
significant dose-response relationship was demonstrated between chronic SCS use
and risk of SCS-related complications in patients with severe asthma. Effective
SCS-sparing strategies might reduce the burden associated with SCS-related
complications in patients with severe asthma.
PMID- 26414881
TI - Quality assessment of occupational health and safety management at the level of
business units making up the organizational structure of a coal mine: a case
study.
AB - The audit of the health and safety management system is understood as a form and
tool of controlling. The objective of the audit is to define whether the
undertaken measures and the obtained results are in conformity with the predicted
assumptions or plans, whether the agreed decisions have been implemented and
whether they are suitable in view of the accepted health and safety policy. This
paper presents the results of an audit examination carried out on the system of
health and safety management between 2002 and 2012 on a group of respondents, the
employees of two mining departments (G-1 and G-2) of Jan, a coal mine. The audit
was carried out using the questionnaire developed by the author based on the
MERIT-APBK survey.
PMID- 26414882
TI - Diagnostic Accuracy of Digital Screening Mammography With and Without Computer
Aided Detection.
AB - IMPORTANCE: After the US Food and Drug Administration (FDA) approved computer
aided detection (CAD) for mammography in 1998, and the Centers for Medicare and
Medicaid Services (CMS) provided increased payment in 2002, CAD technology
disseminated rapidly. Despite sparse evidence that CAD improves accuracy of
mammographic interpretations and costs over $400 million a year, CAD is currently
used for most screening mammograms in the United States. OBJECTIVE: To measure
performance of digital screening mammography with and without CAD in US community
practice. DESIGN, SETTING, AND PARTICIPANTS: We compared the accuracy of digital
screening mammography interpreted with (n = 495 818) vs without (n = 129 807) CAD
from 2003 through 2009 in 323 973 women. Mammograms were interpreted by 271
radiologists from 66 facilities in the Breast Cancer Surveillance Consortium.
Linkage with tumor registries identified 3159 breast cancers in 323 973 women
within 1 year of the screening. MAIN OUTCOMES AND MEASURES: Mammography
performance (sensitivity, specificity, and screen-detected and interval cancers
per 1000 women) was modeled using logistic regression with radiologist-specific
random effects to account for correlation among examinations interpreted by the
same radiologist, adjusting for patient age, race/ethnicity, time since prior
mammogram, examination year, and registry. Conditional logistic regression was
used to compare performance among 107 radiologists who interpreted mammograms
both with and without CAD. RESULTS: Screening performance was not improved with
CAD on any metric assessed. Mammography sensitivity was 85.3% (95% CI, 83.6%
86.9%) with and 87.3% (95% CI, 84.5%-89.7%) without CAD. Specificity was 91.6%
(95% CI, 91.0%-92.2%) with and 91.4% (95% CI, 90.6%-92.0%) without CAD. There was
no difference in cancer detection rate (4.1 in 1000 women screened with and
without CAD). Computer-aided detection did not improve intraradiologist
performance. Sensitivity was significantly decreased for mammograms interpreted
with vs without CAD in the subset of radiologists who interpreted both with and
without CAD (odds ratio, 0.53; 95% CI, 0.29-0.97). CONCLUSIONS AND RELEVANCE:
Computer-aided detection does not improve diagnostic accuracy of mammography.
These results suggest that insurers pay more for CAD with no established benefit
to women.
PMID- 26414883
TI - A Double-Chambered Protein Nanocage Loaded with Thrombin Receptor Agonist Peptide
(TRAP) and gamma-Carboxyglutamic Acid of Protein C (PC-Gla) for Sepsis Treatment.
AB - New protein nanocages are designed bearing two functional proteins, gamma
carboxyglutamic acid of protein C (PC-Gla) and thrombin receptor agonist peptide
(TRAP), and have an anti-septic response. These nanoparticles reduce sepsis
induced organ injury and septic mortality in vivo. Noting that there are
currently no medications for severe sepsis, these results show that novel
nanoparticles can be used to treat sepsis.
PMID- 26414884
TI - Determination of Pain Phenotypes in Knee Osteoarthritis: A Latent Class Analysis
Using Data From the Osteoarthritis Initiative.
AB - OBJECTIVE: Knee osteoarthritis (OA) is a broadly applied diagnosis that may
describe multiple subtypes of pain. The purpose of this study was to identify
phenotypes of knee OA, using measures from the following pain-related domains: 1)
knee OA pathology, 2) psychological distress, and 3) altered pain
neurophysiology. METHODS: Data were selected from a total of 3,494 participants
at visit 6 of the Osteoarthritis Initiative study. Latent class analysis was
applied to the following variables: radiographic OA severity, quadriceps
strength, body mass index, the Charlson Comorbidity Index (CCI), the Center for
Epidemiologic Studies Depression Scale, the Coping Strategies Questionnaire
Catastrophizing subscale, number of bodily pain sites, and knee joint tenderness
at 4 sites. The resulting classes were compared on the following demographic and
clinical factors: age, sex, pain severity, disability, walking speed, and use of
arthritis-related health care. RESULTS: A 4-class model was identified. Class 1
(4% of the study population) had higher CCI scores. Class 2 (24%) had higher knee
joint sensitivity. Class 3 (10%) had greater psychological distress. Class 4
(62%) had lesser radiographic OA, little psychological involvement, greater
strength, and less pain sensitivity. Additionally, class 1 was the oldest, on
average. Class 4 was the youngest, had the lowest disability, and least pain.
Class 3 had the worst disability and most pain. CONCLUSION: Four distinct pain
phenotypes of knee OA were identified. Psychological factors, comorbidity status,
and joint sensitivity appear to be important in defining phenotypes of knee OA
related pain.
PMID- 26414885
TI - Outcomes in Relapsed Graves' Disease Patients Following Radioiodine or Prolonged
Low Dose of Methimazole Treatment.
AB - BACKGROUND: Low doses of antithyroid drugs (ATD) for extended periods may be an
alternative for Graves' disease (GD) patients who relapse after a course of ATD.
METHODS: Patients with GD relapse (n = 238) after discontinuation of ATD therapy
for 12-24 months were retrospectively analyzed in a nonrandomized study.
Radioiodine (RAI) treatment and L-thyroxine replacement was used in 114 patients,
and a low dose of methimazole (MMI; 2.5-7 mg/daily) was used in 124 patients.
Thyroid dysfunction, Graves' ophthalmopathy (GO) evolution, quality of life
(QoL), and body weight were evaluated during the follow-up. RESULTS: The mean
follow-up was 80.8 +/- 35.3 months for the RAI group, and 71.3 +/- 40.3 months
for the low-dose MMI group. No notable side effects were observed in either
group. Thyroid dysfunction was predominant in the RAI group (p < 0.001), and
euthyroidism was more common in the MMI group (p < 0.001). GO deterioration was
mainly evaluated by clinical activity score (CAS)--it was higher in the RAI group
(p < 0.0005) over all periods of follow-up. Multivariate logistic analysis showed
that RAI treatment was associated with no improvement in CAS during follow-up (24
months: OR = 3.51 [CI 1.02-12.03], p < 0.05; 36 months: OR = 8.46 [CI 1.47
48.58], p < 0.05; 48 months: OR = 19.52 [CI 1.70-223.10], p < 0.05; 60 months: OR
= 21.1 [CI 1.5-298], p < 0.05). Kaplan-Meier survival analysis confirmed this
finding (p < 0.0003). Assessment of QoL using the Short Form Health Survey's 36
parameters in stable euthyroid patients (at least six months) was similar in both
groups. The RAI group patients gained more weight (p < 0.005), particularly after
24 months of follow-up. CONCLUSIONS: The use of low doses of MMI is efficient and
safe, and offers better outcomes for GO than RAI treatment. Prolonged low doses
of MMI may be an alternative choice for relapsed GD patients, particularly for GO
patients or for patients who refuse a definitive treatment.
PMID- 26414886
TI - Extrinsic factors can mediate resistance to BRAF inhibition in central nervous
system melanoma metastases.
AB - Here, we retrospectively review imaging of 68 consecutive unselected patients
with BRAF V600-mutant metastatic melanoma for organ-specific response and
progression on vemurafenib. Complete or partial responses were less often seen in
the central nervous system (CNS) (36%) and bone (16%) compared to lung (89%),
subcutaneous (83%), spleen (71%), liver (85%) and lymph nodes/soft tissue (83%),
P < 0.001. CNS was also the most common site of progression. Based on this, we
tested in vitro the efficacy of the BRAF inhibitors PLX4720 and dabrafenib in the
presence of cerebrospinal fluid (CSF). Exogenous CSF dramatically reduced cell
death in response to both BRAF inhibitors. Effective cell killing was restored by
co-administration of a PI-3 kinase inhibitor. We conclude that the efficacy of
vemurafenib is variable in different organs with CNS being particularly prone to
resistance. Extrinsic factors, such as ERK- and PI3K-activating factors in CSF,
may mediate BRAF inhibitor resistance in the CNS.
PMID- 26414888
TI - Recent advances in transcatheter aortic valve replacement for high-risk patients.
AB - Aortic stenosis is the most common valvular heart disease of old age. Patients
with severe aortic stenosis who develop symptoms have a very poor prognosis
without valve intervention. Surgical aortic valve replacement has historically
been the only treatment option for these patients. However a significant minority
are considered inoperable or at high surgical risk and therefore are refused or
decline surgery. In recent years, transcatheter aortic valve replacement has
emerged as an alternative treatment option in these high-risk patients. The aim
of this review is to summarize the current role of transcatheter aortic valve
replacement in contemporary clinical practice including recent advances in
technological and procedural aspects and then discuss future directions.
PMID- 26414887
TI - Detection and proportion of very early dental caries in independent living older
adults.
AB - BACKGROUND AND OBJECTIVES: Dental caries is an important healthcare challenge in
adults over 65 years of age. Integration of oral health screening into non-dental
primary care practice may improve access to preventive dental care for vulnerable
populations such as the elderly. Such integration would require easy, fast, and
accurate early caries detection tools. Primary goal of this study was to evaluate
the diagnostic performance of optical coherence tomography (OCT) imaging for
detecting very early caries in the elderly living in community-based settings.
The International Caries Detection and Assessment System (ICDAS) served as gold
standard. Secondary goal of this study was to provide baseline prevalence data of
very early caries lesions in independent living adults aged 65+ years. MATERIALS
AND METHODS: Seventy-two subjects were recruited from three sites in Southern
California: a retirement community, a senior health fair, and a convalescent
hospital. Clinical examination was performed using the ICDAS visual criteria and
this was followed by OCT imaging. The two-dimensional OCT images (B-scan) were
analyzed with simple software. Locations with a log of back-scattered light
intensity (BSLI) below 2.9 were scored as sound, and areas equaling or exceeding
2.9 BSLI were considered carious. Diagnostic performance of OCT imaging was
compared with ICDAS score. RESULTS: OCT-based diagnosis demonstrated very good
sensitivity (95.1%) and good specificity (85.8%). 54.7% of dentate subjects had
at least one tooth with very early coronal caries. CONCLUSIONS: Early coronal
decay is prevalent in the unrestored pits and fissures of coronal surfaces of
teeth in independent living adults aged 65+ years. Though OCT imaging coupled
with a simple diagnostic algorithm can accurately detect areas of very early
caries in community-based settings, existing devices are expensive and not well
suited for use by non-dental health care providers. Simple, inexpensive, fast,
and accurate tools for early caries detection by field health care providers
working in non-traditional settings are urgently needed to support inter
professional dental health management.
PMID- 26414889
TI - Nitrate reduction by denitrifying anaerobic methane oxidizing microorganisms can
reach a practically useful rate.
AB - Methane in biogas has been proposed to be an electron donor to facilitate
complete nitrogen removal using denitrifying anaerobic methane oxidizing (DAMO)
microorganisms in an anaerobic ammonium oxidation (anammox) reactor, by reducing
the nitrate produced. However, the slow growth and the low activity of DAMO
microorganisms cast a serious doubt about the practical usefulness of such a
process. In this study, a previously established lab-scale membrane biofilm
reactor (MBfR), with biofilms consisting of a coculture of DAMO and anammox
microorganisms, was operated to answer if the DAMO reactor can achieve a nitrate
reduction rate that can potentially be applied for wastewater treatment. Through
progressively increasing nitrate and ammonium loading rates to the reactor, a
nitrate removal rate of 684 +/- 10 mg-N L(-1) d(-1) was achieved after 453 days
of operation. This rate is, to our knowledge, by far the highest reported for
DAMO reactors, and far exceeds what is predicted to be required for nitrate
removal in a sidestream (5.6-135 mg-N L(-1) d(-1)) or mainstream anammox reactor
(3.2-124 mg-N L(-1) d(-1)). Mass balance analysis showed that the nitrite
produced by nitrate reduction was jointly reduced by anammox bacteria at a rate
of 354 +/- 3 mg-N L(-1) d(-1), accompanied by an ammonium removal rate of 268 +/-
2 mg-N L(-1) d(-1), and DAMO bacteria at a rate of 330 +/- 9 mg-N L(-1) d(-1).
This study shows that the nitrate reduction rate achieved by the DAMO process can
be high enough for removing nitrate produced by anammox process, which would
enable complete nitrogen removal from wastewater.
PMID- 26414890
TI - Tracking inorganic foulants irreversibly accumulated on low-pressure membranes
for treating surface water.
AB - While low-pressure membrane filtration processes (i.e., microfiltration and
ultrafiltration) can offer precise filtration than sand filtration, they pose the
problem of reduced efficiency due to membrane fouling. Although many studies have
examined membrane fouling by organic substances, there is still not enough data
available concerning membrane fouling by inorganic substances. The present
research investigated changes in the amounts of inorganic components deposited on
the surface of membrane filters over time using membrane specimens sampled
thirteen times at arbitrary time intervals during pilot testing in order to
determine the mechanism by which irreversible fouling by inorganic substances
progresses. The experiments showed that the inorganic components that primarily
contribute to irreversible fouling vary as filtration continues. It was
discovered that, in the initial stage of operation, the main membrane-fouling
substance was iron, whereas the primary membrane-fouling substances when
operation finished were manganese, calcium, and silica. The amount of iron
accumulated on the membrane increased up to the thirtieth day of operation, after
which it reached a steady state. After the accumulation of iron became static,
subsequent accumulation of manganese was observed. The fact that the removal
rates of these inorganic components also increased gradually shows that the size
of the exclusion pores of the membrane filter narrows as operation continues.
Studying particle size distributions of inorganic components contained in source
water revealed that while many iron particles are approximately the same size as
membrane pores, the fraction of manganese particles slightly smaller than the
pores in diameter was large. From these results, it is surmised that iron
particles approximately the same size as the pores block them soon after the
start of operation, and as the membrane pores narrow with the development of
fouling, they become further blocked by manganese particles approximately the
same size as the narrowed pores. Calcium and silica are assumed to accumulate on
the membrane due to their cross-linking action and/or complex formation with
organic substances such as humic compounds. The present research is the first to
clearly show that the inorganic components that contribute to membrane fouling
differ according to the stage of membrane fouling progression; the information
obtained by this research should enable chemical cleaning or operational control
in accordance with the stage of membrane fouling progression.
PMID- 26414891
TI - The Association between Obstructive Sleep Apnea on Diabetic Kidney Disease: A
Systematic Review and Meta-Analysis.
AB - STUDY OBJECTIVE: This systematic review aims to investigate the association
between obstructive sleep apnea (OSA) and diabetic kidney disease (DKD). METHODS:
MeSH terms and free text searches were performed on MEDLINE, EMBASE, and Cochrane
Database of Systematic Reviews from inception to April 2015. Zetoc and OpenGrey
databases were queried for grey literature, and lastly, hand searches were
carried out. Study selection and quality assessment were conducted by two
authors. One author carried out data extraction, which was checked by other
authors. The relationships between apneahypopnea index (AHI), oxygen desaturation
index (ODI), time spent under 90% oxygen saturation (%TST < 90), and minimum and
mean oxygen saturation (O2) on DKD were examined. RESULTS: Two longitudinal and
ten cross-sectional studies were included for our narrative synthesis, and seven
studies for meta-analysis. Studies that performed multi-variable analysis
demonstrated significant associations between OSA (assessed using either apnea
hypopnea index or ODI) and DKD in type 2 diabetes mellitus (T2DM). This was
confirmed by meta-analysis (pooled OR 1.73, 95% CI: 1.13-2.64). There was some
evidence to suggest that %TST < 90 may have an association with DKD. There was
insufficient evidence to conclude on the relationship between minimum and mean
oxygen saturation on DKD. There was no evidence available on the associations
between OSA and other respiratory parameters in type 1 diabetes mellitus
populations. CONCLUSIONS: There is moderate evidence that OSA is associated with
DKD in patients with T2DM. Large prospective studies with long-term follow up are
needed to assess the possible bi-directional mechanisms between OSA and DKD.
PMID- 26414892
TI - Cortical Thinning and Altered Cortico-Cortical Structural Covariance of the
Default Mode Network in Patients with Persistent Insomnia Symptoms.
AB - STUDY OBJECTIVES: Recent studies have suggested that structural abnormalities in
insomnia may be linked with alterations in the default-mode network (DMN). This
study compared cortical thickness and structural connectivity linked to the DMN
in patients with persistent insomnia (PI) and good sleepers (GS). METHODS: The
current study used a clinical subsample from the longitudinal community-based
Korean Genome and Epidemiology Study (KoGES). Cortical thickness and structural
connectivity linked to the DMN in patients with persistent insomnia symptoms
(PIS; n = 57) were compared to good sleepers (GS; n = 40). All participants
underwent MRI acquisition. Based on literature review, we selected cortical
regions corresponding to the DMN. A seed-based structural covariance analysis
measured cortical thickness correlation between each seed region of the DMN and
other cortical areas. Association of cortical thickness and covariance with sleep
quality and neuropsychological assessments were further assessed. RESULTS:
Compared to GS, cortical thinning was found in PIS in the anterior cingulate
cortex, precentral cortex, and lateral prefrontal cortex. Decreased structural
connectivity between anterior and posterior regions of the DMN was observed in
the PIS group. Decreased structural covariance within the DMN was associated with
higher PSQI scores. Cortical thinning in the lateral frontal lobe was related to
poor performance in executive function in PIS. CONCLUSION: Disrupted structural
covariance network in PIS might reflect malfunctioning of antero-posterior
disconnection of the DMN during the wake to sleep transition that is commonly
found during normal sleep. The observed structural network alteration may further
implicate commonly observed sustained sleep difficulties and cognitive impairment
in insomnia.
PMID- 26414893
TI - Guided Online or Face-to-Face Cognitive Behavioral Treatment for Insomnia: A
Randomized Wait-List Controlled Trial.
AB - STUDY OBJECTIVES: To compare the efficacy of guided online and individual face-to
face cognitive behavioral treatment for insomnia (CBT-I) to a wait-list
condition. METHODS: A randomized controlled trial comparing three conditions:
guided online; face-to-face; wait-list. Posttest measurements were administered
to all conditions, along with 3- and 6-mo follow-up assessments to the online and
face-to-face conditions. Ninety media-recruited participants meeting the
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
criteria for insomnia were randomly allocated to either guided online CBT-I (n =
30), individual face-to-face CBT-I (n = 30), or wait-list (n = 30). RESULTS: At
post-assessment, the online (Cohen d = 1.2) and face-to-face (Cohen d = 2.3)
intervention groups showed significantly larger treatment effects than the wait
list group on insomnia severity (insomnia severity index). Large treatment
effects were also found for the sleep diary estimates (except for total sleep
time), and anxiety and depression measures (for depression only in the face-to
face condition). Face-to-face treatment yielded a statistically larger treatment
effect (Cohen d = 0.9) on insomnia severity than the online condition at all time
points. In addition, a moderate differential effect size favoring face-to-face
treatment emerged at the 3- and 6-mo follow-up on all sleep diary estimates. Face
to-face treatment further outperformed online treatment on depression and anxiety
outcomes. CONCLUSIONS: These data show superior performance of face-to-face
treatment relative to online treatment. Yet, our results also suggest that online
treatment may offer a potentially cost-effective alternative to and complement
face-to-face treatment. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov,
NCT01955850. COMMENTARY: A commentary on this article appears in this issue on
page 13.
PMID- 26414894
TI - Rapid Eye Movement Sleep Behavior Disorder in Paraneoplastic Cerebellar
Degeneration: Improvement with Immunotherapy.
AB - STUDY OBJECTIVES: To report two female patients with paraneoplastic cerebellar
degeneration (PCD) related to breast cancer that presented with rapid eye
movement-sleep behavior disorder (RBD) and improved sleep symptoms with
immunotherapy. METHODS: The two patients were evaluated through clinical scale
and polysomnography before and after therapy with intravenous immunoglobulin.
RESULTS: RBD was successfully treated with immunotherapy in both patients. Score
on the RBD screening questionnaire dropped from 10 to 1 or 0, allied with the
normalization of polysomnographic findings. CONCLUSIONS: A marked improvement in
RBD after immunotherapy in PCD raises the hypothesis that secondary RBD may be an
immune-mediated sleep disorder.
PMID- 26414895
TI - Long-Term Cognitive Impairment in Kleine-Levin Syndrome.
AB - STUDY OBJECTIVES: In Kleine-Levin syndrome (KLS), episodes of hypersomnia,
cognitive, and behavioral disturbances alternate with asymptomatic periods.
Because 50% of patients report decreased academic performances, we evaluated
their cognitive status during asymptomatic periods, determinants of deficits, and
changes during follow-up. METHODS: The cognitive assessment during asymptomatic
periods in all consecutive patients with typical KLS and healthy controls
included the non-verbal intelligence quotient (Raven Progressive Matrices), the
Trail Making Test, the Stroop Color-Word Test, the Wechsler Memory Test, verbal
fluencies, the Free and Cued Learning Memory Test, and the Rey-Osterreith Complex
Figure. Cognitive status was reevaluated after 0.5 to 2 y in 44 patients.
RESULTS: At baseline, compared with the 42 controls, the 122 patients with KLS
exhibited lower non-verbal intelligence quotient, speed of processing, attention,
and reduced retrieval strategies in episodic memory. Higher episode frequency,
shorter episode duration, shorter time since last episode, deeper sleep, and
megaphagia during episodes predicted impaired memory. The visuoconstructional
abilities and non-verbal memory were intact. After a mean follow-up of 1.7 +/-
1.0 y, the episode frequency decreased from 4.6 +/- 4.8 to 1.7 +/- 1.9/y. The
logical reasoning and attention improved, the processing speed remained low, and
the retrieval strategies in verbal memory further worsened. CONCLUSIONS: In this
field study, one-third of patients with KLS have long-term cognitive deficits
affecting retrieval and processing speed. Cognitive function should be
systematically tested in patients with KLS, which appears important to help
patients in their academic studies.
PMID- 26414896
TI - Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep
Apnea Syndrome.
AB - STUDY OBJECTIVES: Children with obstructive sleep apnea syndrome (OSAS) often
experience periods of hypercapnia during sleep, a potent stimulator of cerebral
blood flow (CBF). Considering this hypercapnia exposure during sleep, it is
possible that children with OSAS have abnormal CBF responses to hypercapnia even
during wakefulness. Therefore, we hypothesized that children with OSAS have
blunted CBF response to hypercapnia during wakefulness, compared to snorers and
controls. METHODS: CBF changes during hypercapnic ventilatory response (HCVR)
were tested in children with OSAS, snorers, and healthy controls using diffuse
correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic
baseline were measured for each group. The study was conducted at an academic
pediatric sleep center. RESULTS: Twelve children with OSAS (aged 10.1 +/- 2.5
[mean +/- standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4
[5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 +/- 3 y,
0.5 [0-1.3] events/hour), and 10 controls (11.4 +/- 2.6 y, 0.3 [0.2-0.4]
events/hour) were studied. The fractional CBF change during hypercapnia,
normalized to the change in end-tidal carbon dioxide, was significantly higher in
controls (9 +/- 1.8 %/mmHg) compared to OSAS (7.1 +/- 1.5, P = 0.023) and snorers
(6.7 +/- 1.9, P = 0.025). CONCLUSIONS: Children with OSAS and snorers have
blunted CBF response to hypercapnia during wakefulness compared to controls.
Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights
into physiopathology of OSAS in children, which could lead to further
understanding about the central nervous system complications of OSAS.
PMID- 26414897
TI - A Data-Driven Analysis of the Rules Defining Bilateral Leg Movements during
Sleep.
AB - STUDY OBJECTIVES: The aim of this study was to describe and analyze the
association between bilateral leg movements (LMs) during sleep in subjects with
restless legs syndrome (RLS), in order to eventually support or challenge the
current scoring rules defining bilateral LMs. METHODS: Polysomnographic
recordings of 100 untreated patients with RLS (57 women and 43 males, mean age 57
y) were included. In each recording, we selected as reference all LMs that
occurred during sleep and that were separated from another ipsilateral LM by at
least 10 sec of EMG inactivity. For each reference LM and an evaluation interval
from 5 sec before the onset to 5 sec after the offset of the reference LM, we
evaluated (1) the presence or absence of contralateral leg movement activity and
(2) the distribution of the onset-to-onset and (3) the offset-to-onset
differences between bilateral LMs. RESULTS: We selected a mean of 368 (+/- 222
standard deviation [SD]) reference LMs per subject. For 42% (+/- 22%) of the
reference LMs no contralateral leg movement activity was observed within the
evaluation interval. In 55% (+/- 22%) exactly one and in 3% (+/- 2%) more than
one contralateral LM was observed. A further evaluation of events where exactly
one contralateral LM was observed showed that in most (1) the two LMs were
overlapping (93% +/- 9% SD) and (2) were classified as bilateral according to the
World Association of Sleep Medicine and the International Restless Legs Syndrome
Study Group (WASM/ IRLSSG) (96% +/- 6% SD) and (3) the American Academy of Sleep
Medicine scoring rules (99% +/- 2% SD). Although there was a systematic and
statistically significant difference in standard LM indices during sleep based on
the two different definitions of bilateral LMs, the size of the difference was
not clinically meaningful (maximum individual, absolute difference in LM indices
+/- 2.5). In addition, we found that the duration of LMs within bilateral LM
pairs was longer compared to monolateral LMs and that the duration of the single
LMs in bilateral LM pairs tended to correlate. CONCLUSIONS: The results of this
study indicate that the two current standard scoring rules for the definition of
bilateral LMs during sleep provide largely corresponding classifications in
subjects with RLS and, in a clinical context, can be considered to be equivalent.
PMID- 26414898
TI - C-reactive Protein as a Potential Biomarker of Residual Obstructive Sleep Apnea
Following Adenotonsillectomy in Children.
AB - STUDY OBJECTIVES: Adenotonsillectomy (AT) is first-line treatment for pediatric
obstructive sleep apnea (OSA), with most children having improvements in
polysomnography (PSG). However, many children have residual OSA following AT as
determined through PSG. Identification of a biomarker of residual disease would
be clinically meaningful to detect children at risk. We hypothesize serum high
sensitivity C-reactive protein (hsCRP), an inflammatory biomarker, is predictive
of residual OSA following AT. METHODS: PSG was performed both preoperatively and
postoperatively on children undergoing AT for the diagnosis of OSA. HsCRP serum
concentrations were determined in all children pre-AT, and in most children post
AT. Resolution of OSA after AT was defined by a post-AT apnea-hypopnea index
(AHI) < 1.5/h total sleep time (TST). Residual OSA was defined as a post-AT AHI >
5/h TST, which is considered clinically significant. RESULTS: AT significantly
improved the AHI from 15.9 +/- 16.4 to 4.1 +/- 5.3/h TST in 182 children (P <
0.001). Of 182 children, residual OSA (post-AT AHI > 5) was seen in 46 children
(25%). Among children who had hsCRP levels measured pre- and post-AT (n = 155),
mean hsCRP levels pre-AT were 0.98 +/- 1.91 mg/L and were significantly reduced
post-AT (0.63 +/- 2.24 mg/dL; P = 0.011). Stratification into post-AT AHI groups
corresponding to < 1.5/h TST, 1.5/h TST < AHI < 5/h TST, and AHI > 5/h TST
revealed post-AT hsCRP levels of 0.09 +/- 0.12, 0.57 +/- 2.28, and 1.49 +/- 3.34
mg/L with statistical significance emerging comparing residual AHI > 5/h TST
compared to post-AT AHI < 1.5/h TST (P = 0.006). Hierarchical multivariate
modeling confirmed that pre-AT AHI and post-AT hsCRP levels were most
significantly associated with residual OSA. CONCLUSIONS: Even though AT improves
OSA in most children, residual OSA is frequent. Assessment of post-AT hsCRP
levels emerges as a potentially useful biomarker predicting residual OSA.
PMID- 26414899
TI - Serum Vitamin D Is Significantly Inversely Associated with Disease Severity in
Caucasian Adults with Obstructive Sleep Apnea Syndrome.
AB - STUDY OBJECTIVES: To evaluate vitamin D (25(OH)D) levels in obstructive sleep
apnea syndrome (OSAS) and possible relationships to OSAS severity, sleepiness,
lung function, nocturnal heart rate (HR), and body composition. We also aimed to
compare the 25(OH)D status of a subset of OSAS patients compared to controls
matched for important determinants of both OSAS and vitamin D deficiency (VDD).
METHODS: This was a cross-sectional study conducted at an urban, clinical sleep
medicine outpatient center. We recruited newly diagnosed, Caucasian adults who
had recently undergone nocturnal polysomnography. We compared body mass index
(BMI), body composition (bioelectrical impedance analysis), neck circumference,
sleepiness (Epworth Sleepiness Scale), lung function, and vitamin D status (serum
25-hydrpoxyvitamin D (25(OH)D) across OSAS severity categories and non-OSAS
subjects. Next, using a case-control design, we compared measures of serum
25(OH)D from OSAS cases to non-OSAS controls who were matched for age, gender,
skin pigmentation, sleepiness, season, and BMI. RESULTS: 106 adults (77 male;
median age = 54.5; median BMI = 34.3 kg/m(2)) resident in Dublin, Ireland
(latitude 53 degrees N) were recruited and categorized as non-OSAS or
mild/moderate/severe OSAS. 98% of OSAS cases had insufficient 25(OH)D (< 75
nmol/L), including 72% with VDD (< 50 nmol/L). 25(OH)D levels decreased with OSAS
severity (P = 0.003). 25(OH)D was inversely correlated with BMI, percent body
fat, AHI, and nocturnal HR. Subsequent multivariate regression analysis revealed
that 25(OH)D was independently associated with both AHI (P = 0.016) and nocturnal
HR (P = 0.0419). Our separate case-control study revealed that 25(OH)D was
significantly lower in OSAS cases than matched, non-OSAS subjects (P = 0.001).
CONCLUSIONS: We observed widespread vitamin D deficiency and insufficiency in a
Caucasian, OSAS population. There were significant, independent, inverse
relationships between 25(OH)D and AHI as well as nocturnal HR, a known
cardiovascular risk factor. Further, 25(OH)D was significantly lower in OSAS
cases compared to matched, non-OSAS subjects. We provide evidence that 25(OH)D
and OSAS are related, but the role, if any, of replenishment has not been
investigated.
PMID- 26414900
TI - Variability in Cumulative Habitual Sleep Duration Predicts Waking Functional
Connectivity.
AB - STUDY OBJECTIVES: We examined whether interindividual differences in habitual
sleep patterns, quantified as the cumulative habitual total sleep time (cTST)
over a 2-w period, were reflected in waking measurements of intranetwork and
internetwork functional connectivity (FC) between major nodes of three
intrinsically connected networks (ICNs): default mode network (DMN), salience
network (SN), and central executive network (CEN). METHODS: Resting state
functional magnetic resonance imaging (fMRI) study using seed-based FC analysis
combined with 14-d wrist actigraphy, sleep diaries, and subjective questionnaires
(N = 33 healthy adults, mean age 34.3, standard deviation +/- 11.6 y). Data were
statistically analyzed using multiple linear regression. Fourteen consecutive
days of wrist actigraphy in participant's home environment and fMRI scanning on
day 14 at the Birmingham University Imaging Centre. Seed-based FC analysis on
ICNs from resting-state fMRI data and multiple linear regression analysis
performed for each ICN seed and target. cTST was used to predict FC (controlling
for age). RESULTS: cTST was specific predictor of intranetwork FC when the mesial
prefrontal cortex (MPFC) region of the DMN was used as a seed for FC, with a
positive correlation between FC and cTST observed. No significant relationship
between FC and cTST was seen for any pair of nodes not including the MPFC.
Internetwork FC between the DMN (MPFC) and SN (right anterior insula) was also
predicted by cTST, with a negative correlation observed between FC and cTST.
CONCLUSIONS: This study improves understanding of the relationship between
intranetwork and internetwork functional connectivity of intrinsically connected
networks (ICNs) in relation to habitual sleep quality and duration. The
cumulative amount of sleep that participants achieved over a 14-d period was
significantly predictive of intranetwork and inter-network functional
connectivity of ICNs, an observation that may underlie the link between sleep
status and cognitive performance.
PMID- 26414901
TI - Invariant Natural Killer T Cell Deficiency and Functional Impairment in Sleep
Apnea: Links to Cancer Comorbidity.
AB - STUDY OBJECTIVES: Emerging evidence links obstructive sleep apnea (OSA) with
increased cancer incidence and mortality. Invariant natural killer T (iNKT) cells
play an important role in cancer immunity. We hypothesized that patients with OSA
have low number of circulating invariant natural killer T (iNKT) cells, which may
also be functionally impaired. This study aims to evaluate the frequency of
circulating iNKT cells in OSA. DESIGN: We evaluated the frequency of circulating
iNKT cells by flow cytometry in 33 snorers being assessed for possible OSA. Using
iNKT cell lines, we also evaluated the effect of exposure to hypoxia over 24
hours on apoptosis, cytotoxicity, and cytokine production. SETTING: Teaching
hospital based sleep unit and research laboratory. PATIENTS: Thirty-three snorers
were evaluated: 9 with no OSA (apnea-hypopnea frequency [AHI] < 5/h), 12 with
mild-moderate OSA (AHI 5-30) and 12 with severe OSA (AHI > 30). MEASUREMENTS AND
RESULTS: Patients with severe OSA had considerably fewer iNKT cells (0.18%)
compared to patients with mild-moderate (0.24%) or no OSA (0.35%), P = 0.0026.
The frequency of iNKT cells correlated negatively with apnea-hypopnea index (r =
0.58, P = 0.001), oxygen desaturation index (r = -0.58, P = 0.0003), and SpO2% <
90% (r = -0.5407, P = 0.005). The frequency of iNKT cells increased following 12
months of nCPAP therapy (P = 0.015). Hypoxia resulted in increased apoptosis (P =
0.016) and impaired cytotoxicity (P = 0.035). CONCLUSION: Patients with
obstructive sleep apnea (OSA) have significantly reduced levels of circulating
invariant natural killer T (iNKT) cells and hypoxia leads to impaired iNKT cell
function. These observations may partly explain the increased cancer risk
reported in patients with OSA.
PMID- 26414902
TI - End-Tidal Carbon Dioxide Measurement during Pediatric Polysomnography: Signal
Quality, Association with Apnea Severity, and Prediction of Neurobehavioral
Outcomes.
AB - STUDY OBJECTIVES: To identify the role of end-tidal carbon dioxide (EtCO2)
monitoring during polysomnography in evaluation of children with obstructive
sleep apnea syndrome (OSAS), including the correlation of EtCO2 with other
measures of OSAS and prediction of changes in cognition and behavior after
adenotonsillectomy. DESIGN: Analysis of screening and endpoint data from the
Childhood Adenotonsillectomy Trial, a randomized, controlled, multicenter study
comparing early adenotonsillectomy (eAT) to watchful waiting/supportive care
(WWSC) in children with OSAS. SETTING: Multisite clinical referral settings.
PARTICIPANTS: Children, ages 5.0 to 9.9 y with suspected sleep apnea.
INTERVENTIONS: eAT or WWSC. MEASUREMENTS AND RESULTS: Quality EtCO2 waveforms
were present for >= 75% of total sleep time (TST) in 876 of 960 (91.3%) screening
polysomnograms. Among the 322 children who were randomized, 55 (17%) met
pediatric criteria for hypoventilation. The mean TST with EtCO2 > 50 mmHg was
modestly correlated with apnea-hypopnea index (AHI) (r = 0.33; P < 0.0001) and
with oxygen saturation <= 92% (r = 0.26; P < 0.0001). After adjusting for AHI,
obesity, and other factors, EtCO2 > 50 mmHg was higher in African American
children than others. The TST with EtCO2 > 50 mmHg decreased significantly more
after eAT than WWSC. In adjusted analyses, baseline TST with EtCO2 > 50 mmHg did
not predict postoperative changes in cognitive and behavioral measurements.
CONCLUSIONS: Among children with suspected obstructive sleep apnea syndrome,
overnight end-tidal carbon dioxide (EtCO2) levels are weakly to modestly
correlated with other polysomnographic indices and therefore provide independent
information on hypoventilation. EtCO2 levels improve with adenotonsillectomy but
are not as responsive as AHI and do not provide independent prediction of
cognitive or behavioral response to surgery. CLINICAL TRIAL REGISTRATION:
Childhood Adenotonsillectomy Study for Children with OSAS (CHAT).
ClinicalTrials.gov Identifier #NCT00560859.
PMID- 26414903
TI - Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the
Prospective KORA Age Study.
AB - STUDY OBJECTIVES: To investigate the association between sleep-related
characteristics and cognitive change over 3 years of follow up in an aged
population. METHODS: Sleep characteristics and covariates were assessed at
baseline in a standardized interview and clinical examination of the population
based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined
by telephone interview for cognitive status, TICS-m) was recorded at baseline and
3 years later. RESULTS: At baseline, 82.83% (n = 613) of participants had normal
cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment
(MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct
patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS],
daytime sleepiness [DS] or sleep duration) were considered on a change in
cognitive score with adjustments for potential confounders in generalized linear
regression models. Cognitive decline was more pronounced in individuals with DMS
compared to those with no DMS (beta = 1.33, 95% CI = 0.41-2.24, P < 0.001).
However, the predictive power of DMS was only significant in individuals with
normal cognition and not impaired subjects at baseline. Prolonged sleep duration
increased the risk for cognitive decline in cognitively impaired elderly (beta =
1.86, 95% CI = 0.15-3.57, P = 0.03). Other sleep characteristics (DIS and DS)
were not significantly associated with cognitive decline. CONCLUSIONS: DMS and
long sleep duration were associated with cognitive decline in normal and
cognitively impaired elderly, respectively. The identification of impaired sleep
quality may offer intervention strategies to deter cognitive decline in the
elderly with normal cognitive function.
PMID- 26414904
TI - CD10, BCL6, and MUM1 expression in diffuse large B-cell lymphoma on FNA samples.
AB - BACKGROUND: Gene expression profiling has divided diffuse large B-cell lymphoma
(DLBCL) into 2 main subgroups: germinal center B (GCB) and non-GCB type. This
classification is reproducible by immunohistochemistry using specific antibodies
such as CD10, B-cell lymphoma 6 (BCL6), and multiple myeloma oncogene 1 (MUM1).
Fine-needle aspiration (FNA) plays an important role in the diagnosis of non
Hodgkin lymphoma, and in some cases FNA may be the only available pathological
specimen. The objectives of the current study were to evaluate CD10, BCL6, and
MUM1 immunostaining on FNA samples by testing the CD10, BCL6, and MUM1 algorithm
on both FNA cell blocks (CB) and conventional smears (CS), evaluating differences
in CB and CS immunocytochemical (ICC) performance, and comparing results with
histological data. METHODS: Thirty-eight consecutive DLBCL cases diagnosed by FNA
were studied. Additional passes were used to prepare CB in 22 cases and CS in 16
cases; the corresponding sections and smears were immunostained using CD10, BCL6,
and MUM1 in all cases. The data obtained were compared with histological
immunostaining in 24 cases. RESULTS: ICC was successful in 33 cases (18 CB and 15
CS) and not evaluable in 5 cases (4 CB and 1 CS). The CD10-BCL6-MUM1 algorithm
subclassified DLBCL as GCB (9 cases) and non-GCB (24 cases). ICC data were
confirmed on histologic staining in 24 cases. CONCLUSIONS: CD10, BCL6, and MUM1
ICC staining can be performed on FNA samples. The results herein prove it is
reliable both on CB and CS, and is equally effective and comparable to
immunohistochemistry data.
PMID- 26414905
TI - Asunaprevir (BMS-650032) for the treatment of hepatitis C virus.
AB - Asunaprevir, a second-generation NS3 protease inhibitor of hepatitis C virus
(HCV), exhibits strong antiviral activity against HCV genotypes 1 and 4, but
relatively weak activity against genotypes 2 and 3. For chronic HCV infection,
asunaprevir with daclatasvir as an interferon-free dual treatment achieves a
sustained virologic response of nearly 90% in genotype 1b, and a triple regimen
with beclabuvir achieves an sustained virologic response >90%. Asunaprevir and
daclatasvir dual treatment can be safely and effectively administered to liver
transplant recipients with recurrent HCV. The major drawback of asunaprevir is
its low threshold to resistance, which can be overcome by combining it with other
direct-acting antivirals. Further studies of asunaprevir in combination with
other direct-acting antivirals for the treatment of patients with HCV genotypes 1
or 4 and renal impairment or end-stage renal disease under hemodialysis, HIV
coinfection and liver and/or kidney transplant recipients are warranted.
PMID- 26414907
TI - Economic assessment of FEC-based targeted selective drenching in horses.
AB - In the face of an increased prevalence of drug-resistant cyathostomin
populations, a targeted selective treatment (TST) strategy based on Faecal Egg
Counts (FECs) has been proposed as an alternative management strategy. However,
associated costs may be a barrier to the uptake of this strategy. Our study aims
to provide an economic assessment of FEC-based TST. FECs were determined in a
Welsh pony herd thrice a year from 2010 to 2014. This database was used to
explore the impact of FEC price, sampling strategy (individual or pooled) and
labour-associated costs. Drug price was set at the cheapest level, hence
providing a conservative framework to determine the maximum viable FEC price in
the context of a cost-driven horse industry. The maximum viable FEC price for a
cost-efficient individual based strategy was determined by an in silico bootstrap
approach consisting of randomly sampling 1000 virtual pony herds of various sizes
(1 to 100 ponies) from the available database and estimating the associated costs
(FEC price ranging from ? 1 to ? 10, anthelmintic costs and labour-associated
costs). The costs and benefits of the pooling strategy that consists of basing
the decision to treat on group FEC values were also investigated. This is thought
to reduce FEC-based costs but may result in highly infected individuals being
left undrenched, i.e. in false-negatives, as a result of FEC overdispersion. For
various pool-sizes (1-20 ponies) and various cut-off thresholds (50-200 eggs/g),
we sampled 1000 pony herds in silico to estimate the associated costs and
determine the number of positive ponies within a negative pool. Following these
simulations, pool-based FECs of various sizes were performed on 40 ponies to
compare predictions with real data. Within 4 years, anthelmintic costs were cut
by 80%, albeit with free FECs. In silico estimations suggested that an individual
FEC-based TST would not be cost-efficient in this context for an FEC price above
? 5. With a pooled FEC strategy, the proportion of false-negatives never exceeded
15% of the pool size. The combination of a 14-pony pool and a cut-off value of
150 eggs/g minimized total costs while keeping the number of false negatives to a
reasonable level. Real data obtained from infected ponies however, suggested that
pool size should not exceed 10 individuals, since the inhomogeneous mixing of
faeces of larger pools probably reduced the correlation between average pooled
FECs and the mean of individual FECs. Our study provides an economic framework
that could be valuable for emphasizing the use of FEC-based approaches in the
field.
PMID- 26414906
TI - Detection of Trypanosoma vivax using PCR and LAMP during aparasitemic periods.
AB - Trypanosoma vivax affects cattle herds in Africa and Americas and has been
spreading rapidly in Brazil, through introduction of animals with subclinical
infections and without apparent parasitemia, which makes its diagnosis
challenging. PCR and LAMP are effective in detecting the presence of T. vivax DNA
in situations of low parasitemia. LAMP is simpler and faster technique than PCR,
and can be performed in the field, with limited resources. In this study, the
capacities of conventional PCR and LAMP for detecting T. vivax in bovine blood
samples classified as aparasitemic were evaluated. The capacity of conventional
PCR (56.25%) for detecting positive samples was lower than that of LAMP (93.73%).
This may influence the choice of screening tests for cattle herds infected with
T. vivax.
PMID- 26414908
TI - A Proposed Grading System to Standardize the Description of Renal Papillary
Appearance at the Time of Endoscopy in Patients with Nephrolithiasis.
AB - BACKGROUND AND PURPOSE: The appearance of the renal papillae in patients with
nephrolithiasis can be quite variable and can range from entirely healthy to
markedly diseased. The implications of such findings remain unknown. One
potential reason is the lack of a standardized system to describe such features.
We propose a novel grading scale to describe papillary appearance at the time of
renal endoscopy. METHODS: Comprehensive endoscopic renal assessment and mapping
were performed on more than 300 patients with nephrolithiasis. Recurring abnormal
papillary characteristics were identified and quantified based on degree of
severity. RESULTS: Four unique papillary features were chosen for inclusion in
the PPLA scoring system- ductal Plugging, Pitting, Loss of contour, and Amount of
Randall's plaque. Unique scores are calculated for individual papillae based on
reference examples. CONCLUSIONS: The description and study of renal papillary
appearance in stone formers have considerable potential as both a clinical and
research tool; however, a standardized grading system is necessary before using
it for these purposes.
PMID- 26414910
TI - Enantioselective Synthesis of Hemiaminals via Pd-Catalyzed C-N Coupling with
Chiral Bisphosphine Mono-oxides.
AB - A novel approach to hemiaminal synthesis via palladium-catalyzed C-N coupling
with chiral bisphosphine mono-oxides is described. This efficient new method
exhibits a broad scope, provides a highly efficient synthesis of HCV drug
candidate elbasvir, and has been applied to the synthesis of chiral N,N-acetals.
PMID- 26414911
TI - Extraction Time of Kidneys From Deceased Donors and Impact on Outcomes.
AB - Cold ischemia time (from flush to out-of-ice) and warm ischemia time (from out-of
ice to reperfusion) are known to impact delayed graft function (DGF) rates and
long-term allograft survival following deceased donor kidney transplantation. We
propose an additional ischemia time, extraction time, beginning with aortic cross
clamp and perfusion/cooling of the kidneys, and ending with removal of the
kidneys and placement on ice on the backtable. During this time the kidneys
rewarm, suffering an additional ischemic insult, which may impair transplant
function. We measured extraction times of 576 kidneys recovered and transplanted
locally between January 2006 and December 2008, then linked to Scientific
Registry of Transplant Recipients (SRTR) data for outcomes. Extraction time
ranged from 14 to 123 min, with a mean of 44.7 min. In SRTR-adjusted analyses,
longer extraction time and DGF were statistically associated (odds ratio [OR] =
1.19 per 5 min beyond 60 min, 95% confidence interval [CI] 1.02-1.39, p = 0.03).
Up to 60 min of extraction time, DGF incidence was 27.8%; by 120 min it doubled
to nearly 60%. Although not statistically significant (OR = 1.19, 95% CI 0.96
1.49, p = 0.11), primary nonfunction rate also rose dramatically to nearly 20% by
120 min extraction time. Extraction time is a novel and important factor to
consider when evaluating a deceased donor kidney offer and when strategizing
personnel for kidney recovery.
PMID- 26414909
TI - Different Bla-g T cell antigens dominate responses in asthma versus rhinitis
subjects.
AB - BACKGROUND AND OBJECTIVE: The allergenicity of several German cockroach (Bla-g)
antigens at the level of IgE responses is well established. However, less is
known about the specificity of CD4+ TH responses, and whether differences exist
in associated magnitude or cytokine profiles as a function of disease severity.
METHODS: Proteomic and transcriptomic techniques were used to identify novel
antigens recognized by allergen-specific T cells. To characterize different TH
functionalities of allergen-specific T cells, ELISPOT assays with sets of
overlapping peptides covering the sequences of known allergens and novel antigens
were employed to measure release of IL-5, IFNgamma, IL-10, IL-17 and IL-21.
RESULTS: Using these techniques, we characterized TH responses in a cohort of
adult Bla-g-sensitized subjects, either with (n = 55) or without (n = 17) asthma,
and nonsensitized controls (n = 20). T cell responses were detected for ten known
Bla-g allergens and an additional ten novel Bla-g antigens, representing in total
a 5-fold increase in the number of antigens demonstrated to be targeted by
allergen-specific T cells. Responses of sensitized individuals regardless of
asthma status were predominantly TH 2, but higher in patients with diagnosed
asthma. In asthmatic subjects, Bla-g 5, 9 and 11 were immunodominant, while, in
contrast, nonasthmatic-sensitized subjects responded mostly to Bla-g 5 and 4 and
the novel antigen NBGA5. CONCLUSIONS: Asthmatic and nonasthmatic cockroach
sensitized individuals exhibit similar TH 2-polarized responses. Compared with
nonasthmatics, however, asthmatic individuals have responses of higher magnitude
and different allergen specificity.
PMID- 26414913
TI - Functional hepatocellular regeneration measured by hepatobiliary scintigraphy,
functional regeneration or functional hepatocytes?
PMID- 26414914
TI - The origin of anisotropy and high density of states in the electronic structure
of Cr2GeC by means of polarized soft x-ray spectroscopy and ab initio
calculations.
AB - The anisotropy in the electronic structure of the inherently nanolaminated
ternary phase Cr2GeC is investigated by bulk-sensitive and element selective soft
x-ray absorption/emission spectroscopy. The angle-resolved absorption/emission
measurements reveal differences between the in-plane and out-of-plane bonding at
the (0001) interfaces of Cr2GeC. The Cr L(2, 3), C K, and Ge M1, M(2, 3) emission
spectra are interpreted with first-principles density-functional theory (DFT)
including core-to-valence dipole transition matrix elements. For the Ge 4s
states, the x-ray emission measurements reveal two orders of magnitude higher
intensity at the Fermi level than DFT within the General Gradient Approximation
(GGA) predicts. We provide direct evidence of anisotropy in the electronic
structure and the orbital occupation that should affect the thermal expansion
coefficient and transport properties. As shown in this work, hybridization and
redistribution of intensity from the shallow 3d core levels to the 4s valence
band explain the large Ge density of states at the Fermi level.
PMID- 26414912
TI - Dose Frequency Ranging Pharmacokinetic Study of Tenofovir-Emtricitabine After
Directly Observed Dosing in Healthy Volunteers to Establish Adherence Benchmarks
(HPTN 066).
AB - Oral preexposure prophylaxis (PrEP) trials report disparate efficacy attributed
to variable adherence. HPTN 066 was conducted to establish objective,
quantitative benchmarks for discrete, regular levels of adherence using directly
observed dosing of tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC).
Healthy, HIV-uninfected men and women were randomized to one of four oral
regimens of fixed-dose TDF 300 mg/FTC 200 mg tablet for 5 weeks with all doses
observed: one tablet weekly (one/week), one tablet twice weekly (two/week), two
tablets twice weekly (four/week), or one tablet daily (seven/week). Trough serum
TFV and FTC, peripheral blood mononuclear cell (PBMC), and CD4(+) TFV-diphosphate
(TFV-DP) and FTC-triphosphate (FTC-TP) concentrations were determined throughout
dosing and 2 weeks after the last dose. Rectosigmoidal, semen, and cervicovaginal
samples were collected for drug assessment at end of dosing and 2 weeks later in
a subset of participants. The 49 enrolled participants tolerated the regimens
well. All regimens achieved steady-state concentrations by the second dose for
serum TFV/FTC and by 7 days for PBMC TFV-DP/FTC-TP. Steady-state median TFV-DP
predose concentrations demonstrated dose proportionality: one/week 1.6 fmol/10(6)
PBMCs, two/week 9.1, four/week 18.8, seven/week, 36.3. Further, TFV-DP was
consistently quantifiable 2 weeks after the last dose for the >=4/week regimens.
Adherence benchmarks were identified using receiver operating characteristic
curves, which had areas under the curve >=0.93 for all analytes in serum and
PBMCs. Intersubject and intrasubject coefficients of variation (%CV) ranged from
33% to 63% and 14% to 34%, respectively, for all analytes in serum and PBMCs.
Steady-state PBMC TFV-DP was established earlier and at lower concentrations than
predicted and was the only analyte demonstrating predose concentration dose
proportionality. Steady-state daily dosing serum TFV and PBMC TFV-DP was
consistent with highly effective PrEP clinical trials. HPTN 066 provides
adherence benchmarks for oral TFV/FTC regimens to assist interpreting study
outcomes.
PMID- 26414915
TI - Biomimetic hybrid porous scaffolds immobilized with platelet derived growth
factor-BB promote cellularization and vascularization in tissue engineering.
AB - Development of hybrid scaffolds with synergistic combination of growth factor is
a promising approach to promote early in vivo wound repair and tissue
regeneration. Here, we show the rapid wound healing in Wistar albino rats using
biomimetic collagen-poly(dialdehyde) guar gum based hybrid porous scaffolds
covalently immobilized with platelet derived growth factor-BB. The immobilized
platelet derived growth factor in the hybrid scaffolds not only enhance the total
protein, collagen, hexosamine, and uronic acid contents in the granulation tissue
but also provide stronger tissues. The wound closure analysis reveal that the
complete epithelialization period is 15.4 +/- 0.9 days for collagen
poly(dialdehyde) guar gum-platelet derived growth factor hybrid scaffolds,
whereas it is significantly higher for control, collagen, collagen-
poly(dialdehyde) guar gum and povidine-iodine treated groups. Further, the
histological evaluation shows that the immobilized platelet derived growth factor
in the hybrid scaffolds induced a more robust cellular and vascular response in
the implanted site. Hence, we demonstrate that the collagen-poly(dialdehyde) guar
gum hybrid scaffolds loaded with platelet derived growth factor stimulates
chemotactic effects in the implanted site to promote rapid tissue regeneration
and wound repair without the assistance of antibacterial agents.
PMID- 26414918
TI - Summaries for Patients. Evaluation of Patients With Suspected Acute Pulmonary
Embolism: Best Practice Advice From the Clinical Guidelines Committee of the
American College of Physicians.
PMID- 26414916
TI - Prospective Study on Noninvasive Assessment of Intracranial Pressure in Traumatic
Brain-Injured Patients: Comparison of Four Methods.
AB - Elevation of intracranial pressure (ICP) may occur in many diseases, and
therefore the ability to measure it noninvasively would be useful. Flow velocity
signals from transcranial Doppler (TCD) have been used to estimate ICP; however,
the relative accuracy of these methods is unclear. This study aimed to compare
four previously described TCD-based methods with directly measured ICP in a
prospective cohort of traumatic brain-injured patients. Noninvasive ICP (nICP)
was obtained using the following methods: 1) a mathematical "black-box" model
based on interaction between TCD and arterial blood pressure (nICP_BB); 2) based
on diastolic flow velocity (nICP_FVd); 3) based on critical closing pressure
(nICP_CrCP); and 4) based on TCD-derived pulsatility index (nICP_PI). In time
domain, for recordings including spontaneous changes in ICP greater than 7 mm Hg,
nICP_PI showed the best correlation with measured ICP (R = 0.61). Considering
every TCD recording as an independent event, nICP_BB generally showed to be the
best estimator of measured ICP (R = 0.39; p < 0.05; 95% confidence interval [CI]
= 9.94 mm Hg; area under the curve [AUC] = 0.66; p < 0.05). For nICP_FVd,
although it presented similar correlation coefficient to nICP_BB and marginally
better AUC (0.70; p < 0.05), it demonstrated a greater 95% CI for prediction of
ICP (14.62 mm Hg). nICP_CrCP presented a moderate correlation coefficient (R =
0.35; p < 0.05) and similar 95% CI to nICP_BB (9.19 mm Hg), but failed to
distinguish between normal and raised ICP (AUC = 0.64; p > 0.05). nICP_PI was not
related to measured ICP using any of the above statistical indicators. We also
introduced a new estimator (nICP_Av) based on the average of three methods
(nICP_BB, nICP_FVd, and nICP_CrCP), which overall presented improved statistical
indicators (R = 0.47; p < 0.05; 95% CI = 9.17 mm Hg; AUC = 0.73; p < 0.05).
nICP_PI appeared to reflect changes in ICP in time most accurately. nICP_BB was
the best estimator for ICP "as a number." nICP_Av demonstrated to improve the
accuracy of measured ICP estimation.
PMID- 26414917
TI - An Arthritis-Suppressive and Treg Cell-Inducing CD4+ T Cell Epitope Is Functional
in the Context of HLA-Restricted T Cell Responses.
AB - OBJECTIVE: We previously showed that mycobacterial Hsp70-derived peptide B29
induced B29-specific Treg cells that suppressed experimental arthritis in mice
via cross-recognition of their mammalian Hsp70 homologs. The aim of the current
study was to characterize B29 binding and specific CD4+ T cell responses in the
context of human major histocompatibility complex (MHC) molecules. METHODS:
Competitive binding assays were performed to examine binding of peptide B29 and
its mammalian homologs to HLA molecules. The effect of B29 immunization in HLA
DQ8-transgenic mice with proteoglycan-induced arthritis was assessed, followed by
ex vivo restimulation with B29 to examine the T cell response. Human peripheral
blood mononuclear cells were used to investigate the presence of B29-specific T
cells with immunoregulatory potential. RESULTS: The binding affinity of the B29
peptide was high to moderate for multiple HLA-DR and HLA-DQ molecules, including
those highly associated with rheumatoid arthritis. This binding was considered to
be functional, because B29 immunization resulted in the suppression of arthritis
and T cell responses in HLA-DQ8-transgenic mice. In humans, we demonstrated the
presence and expansion of B29-specific CD4+ T cells, which were cross-reactive
with the mammalian homologs. Using HLA-DR4+ tetramers specific for B29 or the
mammalian homolog mB29b, we showed expansion of cross-reactive T cells,
especially the human FoxP3+ CD4+CD25+ T cell population, after in vitro
stimulation with B29. CONCLUSION: These results demonstrated a conserved fine
specificity and functionality of B29-induced Treg cell responses in the context
of the human MHC. Based on these findings, a path for translation of the
experimental findings for B29 into a clinical immunomodulatory therapeutic
approach is within reach.
PMID- 26414919
TI - A Novel and Simple Modification for Management of Distal Ureter During
Laparoscopic Nephroureterectomy Without Patient Repositioning: A Bulldog Clamp
Technique and Description of Modified Port Placement.
AB - BACKGROUND AND PURPOSE: To describe a novel and pure laparoscopic approach using
a custom-made bulldog clamp with modified port placement for management of distal
ureter during laparoscopic nephroureterectomy. PATIENTS AND METHODS: Between
October 2013 and December 2014, 31 patients found to have upper tract urothelial
carcinoma were treated using this technique. After finishing a standard
laparoscopic transperitoneal nephrectomy in a 45 degrees to 60 degrees
recumbent position, an additional 12-mm trocar was inserted at the lower abdomen
to allow the surgeon to continue dissecting the ureter caudally toward the
bladder wall without repositioning the patient. The intramural ureter was
separated from the surrounding detrusor muscle and down to the bladder mucosa,
until a tent-shaped bladder cuff and intramural ureter could be formed by
retraction in the superior and lateral directions. Then, a custom-made
laparoscopic bulldog clamp was placed at the bottom of the tent-shaped structure
to prevent urine spillage, and the bladder was closed by two-layer running
closure using a barbed suture. RESULTS: All surgeries were completed
uneventfully. The mean operative time and estimated blood loss were 146.6 minutes
and 47.3 mL, respectively. The median duration of the postoperative hospital stay
was 6 days. No complications were noted. There were no positive margins in any
specimen. No patients experienced stone formation or local or bladder recurrence
during the 10.5-month follow-up period. CONCLUSIONS: Our novel technique fully
replicates the open excision technique and conforms to the strictest oncologic
principles while avoiding patient repositioning and the use of staplers (EndoGIA
or Hemolock) to prevent stone formation.
PMID- 26414921
TI - When tackling student debt, information, collaboration is key.
PMID- 26414922
TI - Wombs in labour: Transnational commercial surrogacy in India.
PMID- 26414920
TI - The economic burden of chronic obstructive pulmonary disease from 2004 to 2013.
AB - OBJECTIVES: This study examines the epidemiology and economic impact of chronic
obstructive pulmonary disease (COPD) at a nationwide level in South Korea.
METHODS: This retrospective analysis used the societal cost-of-illness framework,
consisting of direct medical costs, direct non-medical costs, and indirect costs.
In order to analyze the societal costs of patients with COPD, this study used a
data mining and a macro-costing method on data from a South Korean national-level
health survey and a national health insurance claims database from 2004-2013.
RESULTS: The total societal cost of COPD in 2013 was estimated to be $439.9
million for 1,419,914 patients. The direct medical cost for COPD was $214.3
million, which included a hospitalization cost of $96.3 million, an outpatient
cost of $76.4 million, and a pharmaceutical cost of $41.6 million. The direct non
medical cost was estimated at $43.5 million. The indirect overall cost associated
with the morbidity and mortality of COPD was $182.2 million in 2013. CONCLUSIONS:
This study showed that COPD has a major effect on healthcare costs, particularly
direct medical costs. Thus, appropriate long-term interventions are recommended
to lower the economic burden of COPD in South Korea.
PMID- 26414923
TI - Pharmacological approaches in celiac disease.
AB - Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten,
characterized by immune responses toward gluten constituents and the autoantigen
transglutaminase 2. The only current treatment available for celiac disease is a
gluten-free diet, however there are a plethora of therapies in development for
the treatment of celiac disease (e.g. vaccine), management of symptoms while
consuming gluten (e.g. Necator americanus) or adjuvant therapies in conjunction
with the gluten-free diet (e.g. larazotide acetate). Current approaches in
development target barrier function, immune responses, detoxifying gluten or
sequestering gluten. Developing therapies include those targeting environmental
factors, such as the microbiota or proteases.
PMID- 26414924
TI - The rare earth elements in municipal solid waste incinerators ash and promising
tools for their prospecting.
AB - Bottom and fly ashes from Municipal Solid Waste Incinerators (MSWI) are hazardous
products that present concern for their safe management. An attractive option to
reduce their impact both on the environment and the financial commitment is
turning MSWI ashes into secondary raw materials. In this study we present the REE
content and distribution of bottom and fly ashes from MSWI after a highly
effective digestion method and samples analysis by ICP-MS. The chondrite
normalised REE patterns of MSWI bottom and fly ash are comparable with that of
crustal averages, suggesting a main geogenic source. Deviations from typical
crustal pattern (e.g., Eu, Tb) disclose a contribution of likely anthropogenic
provenance. The correlation with major elements indicates possible sources for
REE and facilitates a preliminary resource assessment. Moreover, magnetic
susceptibility measurements can be a useful prospecting method in urban ores made
of MSWI ashes. The relationship between REE and some influencing parameters
(e.g., Pricing Influence Factor) emphasises the importance of MSWI ash as
alternative source of REE and the need of further efforts for REE recovery and
purification from low concentrations but high flows waste.
PMID- 26414925
TI - In Vivo toxicological assessment of biologically synthesized silver nanoparticles
in adult Zebrafish (Danio rerio).
AB - The present study examines the deleterious effect of biologically synthesized
silver nanoparticles in adult zebrafish. Silver nanoparticles (AgNPs) used in the
study were synthesized by treating AgNO3 with aqueous leaves extract of Malva
crispa Linn., a medicinal herb as source of reductants. LC50 concentration of
AgNPs at 96 h was observed as 142.2 MUg/l. In order to explore the underlying
toxicity mechanisms of AgNPs, half of the LC50 concentration (71.1 MUg/l) was
exposed to adult zebrafish for 14 days. Cytological changes and intrahepatic
localization of AgNPs were observed in gills and liver tissues respectively, and
the results concluded a possible sign for oxidative stress. In addition to
oxidative stress the genotoxic effect was observed in peripheral blood cells like
presence of micronuclei, nuclear abnormalities and also loss in cell contact with
irregular shape was observed in liver parenchyma cells. Hence to confirm the
oxidative stress and genotoxic effects the mRNA expression of stress related (MTF
1, HSP70) and immune response related (TLR4, NFKB, IL1B, CEBP, TRF, TLR22) genes
were analyzed in liver tissues and the results clearly concluded that the plant
extract mediated synthesis of AgNPs leads to oxidative stress and immunotoxicity
in adult zebrafish.
PMID- 26414926
TI - Size-dependent atmospheric deposition and inhalation exposure of particle-bound
organophosphate flame retardants.
AB - Atmospheric size-fractionated particles were collected at different heights in an
e-waste recycling zone (QY) and urban Guangzhou (GZ), China and analyzed for
organophosphate flame retardants (OPFRs). The total air concentrations of eight
OPFRs were 130+/-130 and 138+/-127 ng m(-3) in QY and GZ, respectively.
Compositional profiles of chlorinated OPFRs were different between QY and GZ, but
the size distribution patterns of all OPFRs were not significantly different at
different heights. Estimated atmospheric deposition fluxes of OPFRs were 51+/-67
and 55+/-13 MUg m(-2) d(-1) in QY and GZ, respectively, and the coarse particles
(Dp>1.8 MUm) dominated both the dry and wet deposition fluxes. Moreover, not all
particle-bound OPFRs were inhalable and deposited in the human respiratory tract.
The calculated inhalation doses of OPFRs were much lower than the reference
doses, suggesting that potential health risk due to inhalation exposure to
particle-bound OPFRs in the e-waste recycling zone and urban site was low.
PMID- 26414927
TI - Enhanced catalytic activity over MIL-100(Fe) loaded ceria catalysts for the
selective catalytic reduction of NOx with NH3 at low temperature.
AB - The development of catalysts for selective catalytic reduction (SCR) reactions
that are highly active at low temperatures and show good resistance to SO2 and
H2O is still a challenge. In this study, we have designed and developed a high
performance SCR catalyst based on nano-sized ceria encapsulated inside the pores
of MIL-100(Fe) that combines excellent catalytic power with a metal organic
framework architecture synthesized by the impregnation method (IM). Transmission
electron microscopy (TEM) revealed the encapsulation of ceria in the cavities of
MIL-100(Fe). The prepared IM-CeO2/MIL-100(Fe) catalyst shows improved catalytic
activity both at low temperatures and throughout a wide temperature window. The
temperature window for 90% NOx conversion ranges from 196 to 300 degrees C. X-ray
photoelectron spectroscopy (XPS) and in situ diffuse reflectance infrared Fourier
transform spectroscopy (DRIFT) analysis indicated that the nano-sized ceria
encapsulated inside MIL-100(Fe) promotes the production of chemisorbed oxygen on
the catalyst surface, which greatly enhances the formation of the NO2 species
responsible for fast SCR reactions.
PMID- 26414928
TI - High-surface area mesoporous Pt/TiO2 hollow chains for efficient formaldehyde
decomposition at ambient temperature.
AB - Room-temperature catalytic decomposition of formaldehyde (HCHO) is considered as
one of the most main methods for the removal of indoor HCHO due to its facile
reaction conditions. Herein, high-surface area mesoporous Pt/TiO2 hollow chains
were synthesized in high yield by using a simple microwave-hydrothermal route,
followed by a combined NaOH-assisted NaBH4-reduction deposition of Pt
nanoparticles on the as-obtained TiO2 surface. The catalytic activity for HCHO
decomposition was evaluated at room temperature. The prepared Pt/TiO2 hollow
chains with an optimal Pt loading of 0.5 wt.% exhibited high catalytic activity
and recyclability. The apparent reaction rate constant of HCHO oxidation over
this catalyst was approximately 1.42*10(-3) ppm(-1) min(-1), exceeding that of
the commercial Degussa P25 TiO2 with equal Pt content (k=5.36*10(-4) ppm(-1) min(
1)) by a factor of approximately 2.65. The high catalytic activity of the Pt/TiO2
hollow chains could be mainly attributed to the hollow chain-like structure, high
specific surface area, numerous mesopores, and high pore volume of TiO2 support.
Consequently, the catalysts exhibited high adsorption capacity for HCHO, fast
diffusion and transport of gas molecules, and good contact between gases and
active sites. These characteristics enhanced the catalytic activity.
PMID- 26414929
TI - Looking towards objective quality evaluation in colonoscopy: Analysis of visual
gaze patterns.
AB - BACKGROUND AND AIM: There are currently limited training and assessment tools
available to novice endoscopists. A potential tool for the objective assessment
of endoscopist visual search strategy is eye-tracking technology. The aim of this
study is to assess whether eye-tracking technology can be used to differentiate
the visual gaze patterns (VGP) of experienced and novice endoscopists, and to
characterize any differences arising between the two groups. METHOD: With the use
of portable eye-tracking glasses, VGP of novice (n = 20) and experienced (n = 14)
endoscopists were compared while viewing a colonoscopy withdrawal through the
hepatic flexure. Analysis was performed by comparing the central versus
peripheral distribution and the horizontal distribution of novice and experienced
endoscopist fixations, along with comparison of basic eye-tracking metrics.
RESULTS: This study found that experienced endoscopists had a significantly
higher percentage of fixations within the periphery of the screen (13.4% vs
23.0%, P = 0.013). Experienced endoscopists also had a significantly greater
percentage of fixations on the left side of the screen (18.6% vs 33.5%, P =
0.005) that displayed the poorly visualized "inside bend" of the hepatic flexure.
CONCLUSION: This study has detailed specific VGP acquired through expertise,
which can potentially explain why adenomas are regularly missed at the hepatic
flexure during colonoscopy. These may be useful for the training of novice
colonoscopists, and further validation may utilize VGP in the development of an
objective proficiency based curriculum to improve the detection of pathology and
overall quality in endoscopy.
PMID- 26414930
TI - Expression of Wnt3a, Wnt10b, beta-catenin and DKK1 in periodontium during
orthodontic tooth movement in rats.
AB - OBJECTIVE: To investigate the expression of Wnt3a, Wnt10b, beta-catenin and DKK1
in the periodontal ligament (PDL) during orthodontic tooth movement (OTM) in
rats. MATERIALS AND METHODS: Nickel-titanium closed-coil springs were used to
deliver an initial 50 g mesial force to the left maxillary first molars in 30
rats. The force was kept constant for 1, 3, 5, 7, 10 and 14 days until the
animals were sacrificed. The right maxillary molars without force application
served as control. Paraffin-embedded sections of the upper jaws were prepared for
histological and immunohistochemical analyses to detect Wnt3a, Wnt10b, beta
catenin and DKK1 expression in PDL. RESULTS: Wnt3a, Wnt10b, beta-catenin and DKK1
were expressed on both the ipsilateral and contralateral sides of PDL in each
group. After the application of orthodontic force, the expression of beta-catenin
and DKK1 was initially increased and then decreased on both sides, with maximal
levels of expression at day 7 and day 10, respectively. On the compression side,
Wnt3a and Wnt10b levels started to increase at day 5, while on the tension side,
these two molecules began to increase at day 1. Furthermore, the expression
levels of Wnt3a, Wnt10b, and beta-catenin were much stronger on the tension side
than on the compression side at any of the observation points, while DKK1 level
was much higher on the compression side. CONCLUSION: Wnt3a, Wnt10b, beta-catenin
and DKK1 expression may be related to the periodontal tissue remodeling following
the application of an orthodontic force in rats. These observations suggest that
the Wnt/beta-catenin signaling pathway may play a crucial role in periodontal
tissue remodeling during OTM.
PMID- 26414931
TI - Statins Trigger Mitochondrial Reactive Oxygen Species-Induced Apoptosis in
Glycolytic Skeletal Muscle.
AB - AIMS: Although statins are the most widely used cholesterol-lowering agents, they
are associated with a variety of muscle complaints. The goal of this study was to
characterize the effects of statins on the mitochondrial apoptosis pathway
induced by mitochondrial oxidative stress in skeletal muscle using human muscle
biopsies as well as in vivo and in vitro models. RESULTS: Statins increased
mitochondrial H2O2 production, the Bax/Bcl-2 ratio, and TUNEL staining in deltoid
biopsies of patients with statin-associated myopathy. Furthermore, atorvastatin
treatment for 2 weeks at 10 mg/kg/day in rats increased H2O2 accumulation and
mRNA levels and immunostaining of the Bax/Bcl-2 ratio, as well as TUNEL staining
and caspase 3 cleavage in glycolytic (plantaris) skeletal muscle, but not in
oxidative (soleus) skeletal muscle, which has a high antioxidative capacity.
Atorvastatin also decreased the GSH/GSSG ratio, but only in glycolytic skeletal
muscle. Cotreatment with the antioxidant, quercetin, at 25 mg/kg/day abolished
these effects in plantaris. An in vitro study with L6 myoblasts directly
demonstrated the link between mitochondrial oxidative stress following
atorvastatin exposure and activation of the mitochondrial apoptosis signaling
pathway. INNOVATION: Treatment with atorvastatin is associated with mitochondrial
oxidative stress, which activates apoptosis and contributes to myopathy.
Glycolytic muscles are more sensitive to atorvastatin than oxidative muscles,
which may be due to the higher antioxidative capacity in oxidative muscles.
CONCLUSION: There is a link between statin-induced mitochondrial oxidative stress
and activation of the mitochondrial apoptosis signaling pathway in glycolytic
skeletal muscle, which may be associated with statin-associated myopathy.
PMID- 26414933
TI - Electron-Transferred Donor/Acceptor Ferrimagnet with T(C) = 91 K in a Layered
Assembly of Paddlewheel [Ru2] Units and TCNQ.
AB - The donor (D)/acceptor (A) assembly reaction of the paddlewheel-type
diruthenium(II,II) complex [Ru2(2,4,6-F3PhCO2)4(THF)2] (2,4,6-F3PhCO2(-) = 2,4,6
trifluorobenzoate; abbreviated hereafter as [Ru2]) with 7,7,8,8-tetracyano-p
quinodimethane (TCNQ) in a p-xylene/CH2Cl2 solvent system led to the formation of
a two-dimensional layered compound, [{Ru2(2,4,6-F3PhCO2)4}2(TCNQ)].2(p
xylene).2CH2Cl2 (1). As expected from this D/A combination, 1 has a one-electron
transfer ionic state with the D(0.5+)2A(-) formulation. This state formally
derives a heterospin state composed of S = 1 for [Ru(II,II)2], S = 3/2 for
[Ru(II,III)2](+), and S = 1/2 for TCNQ(*-), possibly causing intralayer
ferrimagnetic spin ordering. Most of these types of compounds have an
antiferromagnetic ground state because of the coupling of ferrimagnetically
ordered layers in dipole antiferromagnetic interactions. However, 1 became a
three-dimensional ferrimagnet with T(C) = 91 K because of the presence of
interlayer ferromagnetic interactions.
PMID- 26414934
TI - Electronic structure and excited state dynamics in a dicyanovinyl-substituted
oligothiophene on Au(111).
AB - Dicyanovinyl (DCV)-substituted oligothiophenes are promising donor materials in
vacuum-processed small-molecule organic solar cells. Here, we studied the
structural and the electronic properties of DCV-dimethyl-pentathiophene (DCV5T
Me2) adsorbed on Au(111) from submonolayer to multilayer coverages. Using a multi
technique experimental approach (low-temperature scanning tunneling
microscopy/spectroscopy (STM/STS), atomic force microscopy (AFM), and two-photon
photoemission (2PPE) spectroscopy), we determined the energetic position of
several affinity levels as well as ionization potentials originating from the
lowest unoccupied molecular orbitals (LUMO) and the highest occupied molecular
orbitals (HOMO), evidencing a transport gap of 1.4 eV. Proof of an excitonic
state was found to be a spectroscopic feature located at 0.6 eV below the LUMO
affinity level. With increasing coverage photoemission from excitonic states
gains importance. We were able to track the dynamics of several electronically
excited states of multilayers by means of femtosecond time-resolved 2PPE. We
resolved an intriguing relaxation dynamics involving four processes, ranging from
sub-picosecond (ps) to several hundred ps time spans. These show a tendency to
increase with increasing coverage. The present study provides important
parameters such as energetic positions of transport levels as well as lifetimes
of electronically excited states, which are essential for designing organic
molecule-based optoelectronic devices.
PMID- 26414932
TI - Human Induced Pluripotent Stem Cell NEUROG2 Dual Knockin Reporter Lines Generated
by the CRISPR/Cas9 System.
AB - Human induced pluripotent stem cell (hiPSC) technologies are powerful tools for
modeling development and disease, drug screening, and regenerative medicine.
Faithful gene targeting in hiPSCs greatly facilitates these applications. We have
developed a fast and precise clustered regularly interspaced short palindromic
repeats (CRISPR)/CRISPR associated protein 9 (Cas9) technology-based method and
obtained fluorescent protein and antibiotic resistance dual knockin reporters in
hiPSC lines for neurogenin2 (NEUROG2), an important proneural transcription
factor. Gene targeting efficiency was greatly improved in CRISPR/Cas9-mediated
homology directed recombination (~ 33% correctly targeted clones) compared to
conventional targeting protocol (~ 3%) at the same locus. No off-target events
were detected. In addition, taking the advantage of the versatile applications of
the CRISPR/Cas9 system, we designed transactivation components to transiently
induce NEUROG2 expression, which helps identify transcription factor binding
sites and trans-regulation regions of human NEUROG2. The strategy of using
CRISPR/Cas9 genome editing coupled with fluorescence-activated cell sorting of
neural progenitor cells in a knockin lineage hiPSC reporter platform might be
broadly applicable in other stem cell derivatives and subpopulations.
PMID- 26414935
TI - The use of esophageal stethoscope in a difficult nasogastric tube insertion
during general anesthesia.
PMID- 26414936
TI - In Vivo Mapping of FACT-Histone Interactions Identifies a Role of Pob3 C-terminus
in H2A-H2B Binding.
AB - Histone chaperones assist nucleosomal rearrangements to facilitate the passage of
DNA and RNA polymerases through chromatin. The FACT (facilitates chromatin
transcription) complex is a conserved histone chaperone involved in
transcription, replication, and repair. The complex consists of two major
subunits, Spt16 and SSRP1/Pob3 in mammals and yeast, which engage histones and
DNA by multiple contacts. However, the precise mechanism of FACT function is
largely unclear. Here, we used the genetically installed UV-activatable cross
linker amino acid p-benzoylphenylalanine (pBPA) to map the interaction network of
FACT in living yeast. Unexpectedly, we found the acidic C-terminus of Pob3
forming cross-links to histone H2A and H2B most efficiently. This observation was
independent of the performed cross-linking chemistry since similar histone cross
links were obtained using p-azidophenylalanine (pAzF). Further analyses
identified a C-terminal nuclear localization sequence in Pob3. Its interaction
with Importin-alpha interfered with H2A-H2B binding, which suggests a possible
regulatory role in FACT recruitment to chromatin. Deletion of acidic residues
from the Pob3 C-terminus creates a hydroxyurea-sensitive phenotype in budding
yeast, suggesting a potential role for this domain in DNA replication.
PMID- 26414939
TI - Commentary: Ascertaining Late Effects of Breast Cancer and Its Treatment: Can We
Build a Better Mouse Trap?
PMID- 26414937
TI - Investigating hydroxyl chemical exchange using a variable saturation power
chemical exchange saturation transfer (vCEST) method at 3 T.
AB - PURPOSE: To develop a chemical exchange saturation transfer (CEST) scheme
sensitive to hydroxyl protons at 3 T. Clinical imaging of hydroxyl moieties can
have an impact on osteoarthritis, neuropsychiatric disorders, and cancer. THEORY:
By varying saturation amplitude linearly with frequency offset, the direct water
saturation component of the Z-spectrum is flattened and can be subtracted to
produce a magnetization transfer ratio difference spectrum (MTRdiff ) that
isolates solute resonances. Variable saturation power allows for near
optimization of hydroxyl and amine/amide moieties in one Z-spectrum. METHODS:
Phantom studies were used to test vCEST performance in two environments: (1)
aqueous single-solute (glycogen, glucose); (2) aqueous multiple solute (glycogen
with bovine serum albumin). In vivo vCEST imaging of glycosaminoglycan content in
patellar-femoral cartilage was performed in a subject with history of cartilage
transplant. RESULTS: In solutions with overlapping resonances, vCEST resolves
separate hydroxyl and amine/amide peaks. CEST hydroxyl signal in cartilage is
negligible, but with vCEST, hydroxyl signal ranged from 2 to 5% ppm and showed
distinct contrast between lesions and normal appearing cartilage. CONCLUSION:
Introduced a variable saturation amplitude CEST (vCEST) scheme to improve
sensitivity to exchangeable hydroxyl moieties at 3 T resulting in detection of
hydroxyl in the presence of multiple solutes with overlapping resonances. Magn
Reson Med 76:826-837, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26414938
TI - Cardiovascular Disease Mortality Among Breast Cancer Survivors.
AB - BACKGROUND: Cardiovascular disease (CVD) is of increasing concern among breast
cancer survivors. However, the burden of this comorbidity in this group relative
to the general population, and its temporal pattern, remains unknown. METHODS: We
compared deaths due to CVD in a population-based sample of 1,413 women with
incident breast cancer diagnosed in 1996-1997, and 1,411 age-matched women
without breast cancer. Date and cause of death through December 31, 2009 were
assessed through the national death index and covariate data was gathered through
structured interviews and medical record abstraction. Hazard ratios (HR) and 95%
confidence intervals were calculated using Cox regression for overall mortality
(HR) and CVD-specific death (cause-specific HR). Subdistribution HRs for CVD
death were estimated from the Fine-Gray model. RESULTS: Risk of death was greater
among breast cancer survivors compared with women without breast cancer (HR: 1.8
[1.5, 2.1]). An increase in CVD-related death among breast cancer survivors was
evident only 7 years after diagnosis (years 0-7, cause-specific HR: 0.80 [0.53,
1.2], subdistribution HR: 0.59 [0.40, 0.87]); years 7+, cause-specific HR: 1.8
[1.3, 2.5], subdistribution HR: 1.9 [1.4, 2.7]; P interaction: 0.001). An
increase in CVD-related mortality was observed among breast cancer survivors
receiving chemotherapy. CONCLUSIONS: Breast cancer survivors are at greater risk
for CVD-related mortality compared with women without breast cancer and this
increase in risk is manifested approximately 7 years after diagnosis. Efforts
should be made to identify risk factors and interventions that can be employed
during this brief window to reduce the excess burden of CVD in this vulnerable
population.
PMID- 26414940
TI - Commentary: The Urban Environment and Violence: Moving Toward a Dynamic
Understanding of Space.
PMID- 26414941
TI - Mapping Activity Patterns to Quantify Risk of Violent Assault in Urban
Environments.
AB - BACKGROUND: We collected detailed activity paths of urban youth to investigate
the dynamic interplay between their lived experiences, time spent in different
environments, and risk of violent assault. METHODS: We mapped activity paths of
10- to 24-year-olds, including 143 assault patients shot with a firearm, 206
assault patients injured with other types of weapons, and 283 community controls,
creating a step-by-step mapped record of how, when, where, and with whom they
spent time over a full day from waking up until going to bed or being assaulted.
Case-control analyses compared cases with time-matched controls to identify risk
factors for assault. Case-crossover analyses compared cases at the time of
assault with themselves earlier in the day to investigate whether exposure
increases acted to the trigger assault. RESULTS: Gunshot assault risks included
being alone (odds ratio [OR] = 1.6, 95% confidence interval [CI] = 1.3, 1.9) and
were lower in areas with high neighbor connectedness (OR = 0.7, 95% CI = 0.6,
0.8). Acquiring a gun (OR = 1.4, 95% CI = 1.1, 1.6) and entering areas with more
vacancy, violence, and vandalism (OR = 1.7, 95% CI = 1.1, 2.7) appeared to
trigger the risk of getting shot shortly thereafter. Nongunshot assault risks
included being in areas with recreation centers (OR = 1.2, 95% CI = 1.1, 1.4).
Entering an area with higher truancy (OR = 1.6, 95% CI = 1.1, 2.5) and more
vacancy, violence, and vandalism appeared to trigger the risk of nongunshot
assault. Risks varied by age group. CONCLUSIONS: We achieved a large-scale study
of the activities of many boys, adolescents, and young men that systematically
documented their experiences and empirically quantified risks for violence.
Working at a temporal and spatial scale that is relevant to the dynamics of this
phenomenon gave novel insights into triggers for violent assault.
PMID- 26414942
TI - Distributed Lag Models: Examining Associations Between the Built Environment and
Health.
AB - Built environment factors constrain individual level behaviors and choices, and
thus are receiving increasing attention to assess their influence on health.
Traditional regression methods have been widely used to examine associations
between built environment measures and health outcomes, where a fixed,
prespecified spatial scale (e.g., 1 mile buffer) is used to construct environment
measures. However, the spatial scale for these associations remains largely
unknown and misspecifying it introduces bias. We propose the use of distributed
lag models (DLMs) to describe the association between built environment features
and health as a function of distance from the locations of interest and
circumvent a-priori selection of a spatial scale. Based on simulation studies, we
demonstrate that traditional regression models produce associations biased away
from the null when there is spatial correlation among the built environment
features. Inference based on DLMs is robust under a range of scenarios of the
built environment. We use this innovative application of DLMs to examine the
association between the availability of convenience stores near California public
schools, which may affect children's dietary choices both through direct access
to junk food and exposure to advertisement, and children's body mass index z
scores.
PMID- 26414944
TI - Functionalization of a Collagen-Hydroxyapatite Scaffold with Osteostatin to
Facilitate Enhanced Bone Regeneration.
AB - Defects within bones caused by trauma and other pathological complications may
often require the use of a range of therapeutics to facilitate tissue
regeneration. A number of approaches have been widely utilized for the delivery
of such therapeutics via physical encapsulation or chemical immobilization
suggesting significant promise in the healing of bone defects. The study focuses
on the chemical immobilization of osteostatin, a pentapeptide of the parathyroid
hormone (PTHrP107-111), within a collagen-hydroxyapatite scaffold. The chemical
attachment method via crosslinking supports as little as 4% release of the
peptide from the scaffolds after 21 d whereas non-crosslinking leads to 100% of
the peptide being released by as early as 4 d. In vitro characterization
demonstrates that this cross-linking method of immobilization supports a pro
osteogenic effect on osteoblasts. Most importantly, when implanted in a critical
sized calvarial defect within a rat, these scaffolds promote significantly
greater new bone volume and area compared to nonfunctionalized scaffolds (**p <
0.01) and an empty defect control (***p < 0.001). Collectively, this study
suggests that such an approach of chemical immobilization offers greater
spatiotemporal control over growth factors and can significantly modulate tissue
regeneration. Such a system may be adopted for a range of different proteins and
thus offers the potential for the treatment of various complex pathologies that
require localized mediation of drug delivery.
PMID- 26414946
TI - Is lower base rate detrimental to transcatheter aortic valve implantation
patients requiring pacemakers?
AB - Sudden cardiac death related to polymorphic ventricular tachycardia/ventricular
fibrillation has been well reported post atrioventricular junction ablation. The
practice of faster pacing rate immediately after atrioventricular junction
ablation is well recognized to decrease the risk of sudden cardiac death. We
propose that this practice (faster pacing rate) be implemented in patients who
need permanent pacemakers secondary to transcatheter aortic valve implantation
(or even surgical aortic valve interventions).
PMID- 26414945
TI - Serum osteopontin levels in relation to bone mineral density and bone turnover
markers in postmenopausal women.
AB - Osteopontin (OPN) is an extracellular matrix protein that is expressed in bone
cells such as osteoblast and osteocytes and associated with bone turnover and
bone mineral density (BMD) in postmenopausal women. Here, we aimed to investigate
the relationship between circulating OPN levels and BMD in postmenopausal women
in Southern China. A total of 362 postmenopausal women were consecutively
recruited into this study from 2011-2013. Serum levels of OPN, receptor activator
of nuclear factor kappa B (NF-kappaB) ligand (RANKL), and bone turnover markers
were analyzed. BMD was measured by dual energy X-ray absorptiometry. Osteoporosis
and osteopenia were diagnosed according to the World Health Organization
criteria. Serum OPN levels were remarkably higher in the osteoporotic group than
those in the osteopenic and normal groups (all p < 0.001). The cut-off value of
OPN for diagnosing postmenopausal osteoporosis was 10.1 ng/mL, which had a
sensitivity of 89.5%, a specificity of 70.8%, and an area under curve of 0.953.
Serum OPN was negatively correlated with parathyroid hormone (PTH), lumbar spine
BMD, and femoral neck BMD (r = -0.25, p = 0.004; r = -0.66, p < 0.001; r = -0.28,
p = 0.001; respectively) and positively associated with type I procollagen amino
terminal propeptide (PINP), carboxy-terminal cross-linking telopeptide of type I
collagen (CTX), and RANKL (r = 0.20, p = 0.020; r = 0.17, p = 0.036; r = 0.19, p
= 0.028, respectively) in the osteoporotic group. In multiple regression
analyses, lumbar spine BMD, PTH and RANKL were the predictors for serum OPN
levels. In conclusion, OPN serum levels are negatively related to BMD and
positively correlated with bone turnover levels in this group of Chinese
postmenopausal women.
PMID- 26414943
TI - Prenatal DDT and DDE exposure and child IQ in the CHAMACOS cohort.
AB - Although banned in most countries, dichlorodiphenyl-trichloroethane (DDT)
continues to be used for vector control in some malaria endemic areas. Previous
findings from the Center for the Health Assessment of Mothers and Children of
Salinas (CHAMACOS) cohort study found increased prenatal levels of DDT and its
breakdown product dichlorodiphenyl-dichloroethylene (DDE) to be associated with
altered neurodevelopment in children at 1 and 2years of age. In this study, we
combined the measured maternal DDT/E concentrations during pregnancy obtained for
the prospective birth cohort with predicted prenatal DDT and DDE levels estimated
for a retrospective birth cohort. Using generalized estimating equation (GEE) and
linear regression models, we evaluated the relationship of prenatal maternal DDT
and DDE serum concentrations with children's cognition at ages 7 and 10.5years as
assessed using the Full Scale Intelligence Quotient (IQ) and 4 subtest scores
(Working Memory, Perceptual Reasoning, Verbal Comprehension, and Processing
Speed) of the Wechsler Intelligence Scale for Children (WISC). In GEE analyses
incorporating both age 7 and 10.5 scores (n=619), we found prenatal DDT and DDE
levels were not associated with Full Scale IQ or any of the WISC subscales (p
value>0.05). In linear regression analyses assessing each time point separately,
prenatal DDT levels were inversely associated with Processing Speed at age 7years
(n=316), but prenatal DDT and DDE levels were not associated with Full Scale IQ
or any of the WISC subscales at age 10.5years (n=595). We found evidence for
effect modification by sex. In girls, but not boys, prenatal DDE levels were
inversely associated with Full Scale IQ and Processing Speed at age 7years. We
conclude that prenatal DDT levels may be associated with delayed Processing Speed
in children at age 7years and the relationship between prenatal DDE levels and
children's cognitive development may be modified by sex, with girls being more
adversely affected.
PMID- 26414947
TI - Production of a Bilayered Self-Assembled Skin Substitute Using a Tissue
Engineered Acellular Dermal Matrix.
AB - Our bilayered self-assembled skin substitutes (SASS) are skin substitutes showing
a structure and functionality very similar to native human skin. These constructs
are used, in life-threatening burn wounds, as permanent autologous grafts for the
treatment of such affected patients even though their production is exacting. We
thus intended to shorten their current production time to improve their clinical
applicability. A self-assembled decellularized dermal matrix (DM) was used. It
allowed the production of an autologous skin substitute from patient's cells. The
characterization of SASS reconstructed using a decellularized dermal matrix (SASS
DM) was performed by histology, immunofluorescence, transmission electron
microscopy, and uniaxial tensile analysis. Using the SASS-DM, it was possible to
reduce the standard production time from about 8 to 4 and a half weeks. The
structure, cell differentiation, and mechanical properties of the new skin
substitutes were shown to be similar to the SASS. The decellularization process
had no influence on the final microstructure and mechanical properties of the DM.
This model, by enabling the production of a skin substitute in a shorter time
frame without compromising its intrinsic tissue properties, represents a
promising addition to the currently available burn and wound treatments.
PMID- 26414948
TI - Genome-wide identification and expression analysis of WNK kinase gene family in
rice.
AB - Eukaryotic protein kinases represent one of the largest gene families involved in
diverse regulatory functions. WNK (With No Lysine) kinases are members of ser/thr
protein kinase family, which lack conserved catalytic lysine (K) residue at
protein kinase subdomain II and is replaced by either asparagine, serine or
glycine residues. They are involved in regulation of flowering time, circadian
rhythms and abiotic stresses in Arabidopsis thaliana. In the present study, we
have identified 9 members of WNK in rice, showed resemblance to Arabidopsis and
human WNK and clustered into five main clades phylogenetically. The predicted
genes structure, bonafide conserved signature motif and domains strongly support
their identity, as members of WNK kinase family. We have analyzed their
chromosomal distribution, physio-chemical properties, subcellular localizations
and cis-elements in the promoter regions in silico. Further, transcript analysis
of OsWNK by qRT-PCR revealed their differential regulation in tissue specific and
abiotic stresses libraries. In conclusion, the identification of nine OsWNK and
transcript level expression pattern under abiotic stress using qRT-PCR in rice
will significantly contribute towards the understanding of WNK genes in monocots
and thus provide a set up for functional genomics studies of WNK protein kinases.
PMID- 26414949
TI - In silico approaches for the identification of virulence candidates amongst
hypothetical proteins of Mycoplasma pneumoniae 309.
AB - Mycoplasma pneumoniae type 2a strain 309 is a simplest known bacterium and is the
primary cause of community acquired pneumonia in the children. It mainly causes
severe atypical pneumonia as well as several other non-pulmonary manifestations
such as neurological, hepatic, hemolytic anemia, cardiac diseases and
polyarthritis. The size of M. pneumoniae genome (Accession number: NC_016807.1)
is relatively smaller as compared to other bacteria and contains 707 functional
proteins, in which 204 are classified as hypothetical proteins (HPs) because of
the unavailability of experimentally validated functions. The functions of the
HPs were predicted by integrating a variety of protein classification systems,
motif discovery tools as well as methods that are based on characteristic
features obtained from the protein sequence and metabolic pathways. The probable
functions of 83HPs were predicted successfully. The accuracy of the diverse tools
used in the adopted pipeline was evaluated on the basis of statistical techniques
of Receiver Operating Characteristic (ROC), which indicated the reliability of
the functional predictions. Furthermore, the virulent HPs present in the set of
83 functionally annotated proteins were predicted by using the Bioinformatics
tools and the conformational behaviours of the proteins with highest virulence
scores were studied by using the molecular dynamics (MD) simulations. This study
will facilitate in the better understanding of various drug resistance and
pathogenesis mechanisms present in the M. pneumoniae and can be utilized in
designing of better therapeutic agents.
PMID- 26414950
TI - Multiple ligand simultaneous docking (MLSD): A novel approach to study the effect
of inhibitors on substrate binding to PPO.
AB - Multiple ligand simultaneous docking, a computational approach is used to study
the concurrent interactions between substrate and the macromolecule binding
together in the presence of an inhibitor. The present investigation deals with
the study of the effect of different inhibitors on binding of substrate to the
protein Polyphenoloxidase (PPO). The protein was isolated from Mucuna pruriens
and confirmed as tyrosinases involved in L-DOPA production. The activity was
measured using different inhibitors at different concentrations taking catechol
as substrate. A high-throughput binding study was conducted to compare the
binding orientations of individual ligands and multiple ligands employing
Autodock 4.2. The results of single substrate docking showed a better binding of
urea with the binding energy of -3.48 kJ mol(-1) and inter molecular energy of
3.48 kJ mol(-1) while the results of MLSD revealed that ascorbic acid combined
with the substrate showed better inhibition with a decreased binding energy of
2.37 kJ mol(-1).
PMID- 26414951
TI - Production of Early Diploid Males by European Colonies of the Invasive Hornet
Vespa velutina nigrithorax.
AB - The invasive yellow-legged hornet Vespa velutina nigrithorax was accidentally
introduced in Europe in the early 2000s. As is the case in colonies of other wasp
and hornet species, V. velutina colonies are known to produce sexuals (males and
new queens) at the end of the summer. We show that early-stage colonies in French
populations frequently produce males well before the usual reproductive period.
The vast majority of the males produced are diploid, which is consistent with the
loss of genetic diversity previously reported in introduced populations in
France. Since males do not participate in colony activities, the production of
early diploid males at the expense of workers is expected to hamper colony growth
and, ultimately, decrease the expansion of the species in its invasive range in
Europe.
PMID- 26414952
TI - Disentangling Brain Graphs: A Note on the Conflation of Network and Connectivity
Analyses.
AB - Understanding the human brain remains the holy grail in biomedical science, and
arguably in all of the sciences. Our brains represent the most complex systems in
the world (and some contend the universe) comprising nearly 100 billion neurons
with septillions of possible connections between them. The structure of these
connections engenders an efficient hierarchical system capable of consciousness,
as well as complex thoughts, feelings, and behaviors. Brain connectivity and
network analyses have exploded over the last decade due to their potential in
helping us understand both normal and abnormal brain function. Functional
connectivity (FC) analysis examines functional associations between time series
pairs in specified brain voxels or regions. Brain network analysis serves as a
distinct subfield of connectivity analysis, in which associations are quantified
for all time series pairs to create an interconnected representation of the brain
(a brain network), which allows studying its systemic properties. While
connectivity analyses underlie network analyses, the subtle distinction between
the two research areas has generally been overlooked in the literature, with them
often being referred to synonymously. However, developing more useful analytic
methods and allowing for more precise biological interpretations require
distinguishing these two complementary domains.
PMID- 26414953
TI - Cancer risks in twins and singletons from twin and non-twin families.
AB - The unique intrauterine environment has been proposed to put twins at increased
risk of certain cancers compared to singletons, still large population
comparisons have generally indicated lower risks in twins. To improve the
understanding of potential twin influence on cancer we compared twins to their
singletons siblings, to target a unique twinning influence. Singletons from twin
families were contrasted to singletons from non-twin families to further capture
potential twin family influence on risk of cancer. Family relations were
identified using the Swedish Multi-Generation Register. Among individuals born
between 1932 and 1958, 49,156 twins and N = 35,227 singletons were identified
from 18,098 unique twin families. All incident cases of specific cancer types
were identified in the National Cancer Register up to the end of 2007.
Standardized survival functions were estimated using weighted Cox proportional
hazard regression and the corresponding cumulative risks plotted against age.
Overall, primary cancers were identified in 9% and 18% of all male and female
twins, compared to 11% and 19% of their male and female singleton siblings. When
specific cancer sites were compared using standardized cumulative risk plots, no
consistent statistically significant differences were noted either between twins
and singletons of twin families or between singletons of twin and non-twin
families. Despite a different intrauterine experience, twinning does not seem to
have any greater negative influence on life-time risks of cancer. The findings
also indicate that twin family membership has no substantial influence on cancer
risks.
PMID- 26414954
TI - Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly
Associated with Reduced Mortality at Advanced Ages.
AB - On the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy
Longevity Survey (CLHLS) and Cox proportional hazard model, the present study
demonstrates that interactions between carrying FOXO1A-209 genotypes and tea
drinking are significantly associated with lower risk of mortality at advanced
ages. Such a significant association is replicated in two independent Han Chinese
CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p =
0.003-0.016 in the combined dataset). We found the associations between tea
drinking and reduced mortality are much stronger among carriers of the FOXO1A-209
genotype compared to non-carriers, and drinking tea is associated with a reversal
of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a
substantially increased mortality risk to substantially reduced mortality risk at
advanced ages. The impacts are considerably stronger among those who carry two
copies of the FOXO1A minor allele than those who carry one copy. On the basis of
previously reported experiments on human cell models concerning FOXO1A-by-tea
compounds interactions, we speculate that results in the present study indicate
that tea drinking may inhibit FOXO1A-209 gene expression and its biological
functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as
reported in the literature) and offers protection against mortality risk at
oldest-old ages. Our empirical findings imply that the health outcomes of
particular nutritional interventions, including tea drinking, may, in part,
depend upon individual genetic profiles, and the research on the effects of
nutrigenomics interactions could potentially be useful for rejuvenation therapies
in the clinic or associated healthy aging intervention programs.
PMID- 26414956
TI - 'There is fear but there is no other work': a preliminary qualitative exploration
of the experience of sex workers in eastern Democratic Republic of Congo.
AB - Two decades of conflict and insecurity have had a devastating impact on many in
the Democratic Republic of Congo (DRC), including marginalised groups such as sex
workers. In the province of North Kivu, many residents face desperate conditions
that render them vulnerable to exploitation and abuse. As a result, many turn to
the sex trade in what can often be described as 'survival sex'. This small-scale
qualitative study explores the experience of urban sex workers in the eastern
region of the DRC. Sex workers were recruited at their place of business and
asked to participate in a semi-structured interview. Eight participants were
recruited, including seven women and one man. Our analysis identified several
themes: (1) economic hardship as a catalyst for joining the sex trade, (2)
significant work-related violence and (3) a paucity of available resources or
assistance. Responses to specific prompts indicated that sex workers do not trust
law enforcement and there are significant barriers to both medical care and local
resources. Further studies of this vulnerable population and its needs are
encouraged in order to develop programmes that provide the means to manage the
hazards of their work and obtain an alternative source of income.
PMID- 26414957
TI - Polypoidal Choroidal Vasculopathy: A Distinct Disease or Manifestation of Many?
PMID- 26414955
TI - Altered Neuroinflammation and Behavior after Traumatic Brain Injury in a Mouse
Model of Alzheimer's Disease.
AB - Traumatic brain injury (TBI) has acute and chronic sequelae, including an
increased risk for the development of Alzheimer's disease (AD). TBI-associated
neuroinflammation is characterized by activation of brain-resident microglia and
infiltration of monocytes; however, recent studies have implicated beta-amyloid
as a major manipulator of the inflammatory response. To examine neuroinflammation
after TBI and development of AD-like features, these studies examined the effects
of TBI in the presence and absence of beta-amyloid. The R1.40 mouse model of
cerebral amyloidosis was used, with a focus on time points well before robust AD
pathologies. Unexpectedly, in R1.40 mice, the acute neuroinflammatory response to
TBI was strikingly muted, with reduced numbers of CNS myeloid cells acquiring a
macrophage phenotype and decreased expression of inflammatory cytokines. At
chronic time points, macrophage activation substantially declined in non-Tg TBI
mice; however, it was relatively unchanged in R1.40 TBI mice. The persistent
inflammatory response coincided with significant tissue loss between 3 and 120
days post-injury in R1.40 TBI mice, which was not observed in non-Tg TBI mice.
Surprisingly, inflammatory cytokine expression was enhanced in R1.40 mice
compared with non-Tg mice, regardless of injury group. Although R1.40 TBI mice
demonstrated task-specific deficits in cognition, overall functional recovery was
similar to non-Tg TBI mice. These findings suggest that accumulating beta-amyloid
leads to an altered post-injury macrophage response at acute and chronic time
points. Together, these studies emphasize the role of post-injury
neuroinflammation in regulating long-term sequelae after TBI and also support
recent studies implicating beta-amyloid as an immunomodulator.
PMID- 26414958
TI - Theoretical Study on the Excited Electronic States of CHCl: Application to
Photodissociation at 193 nm.
AB - We present herein a high-level ab initio study on the electronic excited states
of CHCl using the internally contracted multireference configuration interaction
method including Davidson correction (icMRCI+Q). A total of 13 electronic states
with energy of up to 7 eV have been investigated. The vertical transition
energies, oscillator strengths, electron configurations, and transitions of the
electronic states of CHCl have been calculated at the icMRCI+Q/aug-cc-pv(5+d)Z
level. The potential energy curves of the electronic states have been studied
along the H-C-Cl angle, the C-H bond length, and the C-Cl bond length,
respectively. Our theoretical study has provided comprehensive information for
understanding the interaction and the behavior of the electronic excited states
of CHCl. In particular, the excited state involved in the 193 nm
photodissociation as well as the corresponding dissociation dynamics have been
discussed on the basis of our calculation results. The present study should shed
more light on the photochemistry of CHCl in the ultraviolet region.
PMID- 26414959
TI - Three-Dimensional Culture of Functional Adult Rabbit Lacrimal Gland Epithelial
Cells on Decellularized Scaffold.
AB - Aqueous tear-deficient dry eye disease is a multifactorial chronic disorder, in
which the lacrimal gland fails to produce enough tears to maintain a healthy
ocular surface. Some severe cases may develop corneal damage and significant
vision loss. Treatment primarily involves palliation using ocular surface
lubricants, but can only provide temporary relief. Construction of a
bioengineered lacrimal gland having functional secretory epithelial cells is a
potentially promising option for providing long-term relief to severe dry eye
patients. Using sphere-forming culture techniques, we cultured adult rabbit
lacrimal gland progenitor cells and prepared a lacrimal gland scaffold by
decellularization. When progenitor cells were seeded onto the decellularized
scaffold, they formed duct- and acinar-like structures in the three-dimensional
culture system. Lacrimal gland epithelial cells showed good cell viability, cell
differentiation, and secretory function in decellularized lacrimal gland matrix,
as indicated by morphology, immunostaining, and beta-hexosaminidase secretion
assay. This study demonstrated the potential suitability of utilizing tissue
specific progenitor cells and a tissue-derived bioscaffold for lacrimal gland
restoration.
PMID- 26414960
TI - Diversity of Interstitial Lung Fibroblasts Is Regulated by Platelet-Derived
Growth Factor Receptor alpha Kinase Activity.
AB - Epithelial-mesenchymal cell interactions and factors that control normal lung
development are key players in lung injury, repair, and fibrosis. A number of
studies have investigated the roles and sources of epithelial progenitors during
lung regeneration; such information, however, is limited in lung fibroblasts.
Thus, understanding the origin, phenotype, and roles of fibroblast progenitors in
lung development, repair, and regeneration helps address these limitations. Using
a combination of platelet-derived growth factor receptor alpha-green fluorescent
protein (PDGFRalpha-GFP) reporter mice, microarray, real-time polymerase chain
reaction, flow cytometry, and immunofluorescence, we characterized two distinct
interstitial resident fibroblasts, myo- and matrix fibroblasts, and identified a
role for PDGFRalpha kinase activity in regulating their activation during lung
regeneration. Transcriptional profiling of the two populations revealed a myo-
and matrix fibroblast gene signature. Differences in proliferation, smooth muscle
actin induction, and lipid content in the two subpopulations of PDGFRalpha
expressing fibroblasts during alveolar regeneration were observed. Although
CD140alpha(+)CD29(+) cells behaved as myofibroblasts, CD140alpha(+)CD34(+)
appeared as matrix and/or lipofibroblasts. Gain or loss of PDGFRalpha kinase
activity using the inhibitor nilotinib and a dominant-active PDGFRalpha-D842V
mutation revealed that PDGFRalpha was important for matrix fibroblast
differentiation. We demonstrated that PDGFRalpha signaling promotes alveolar
septation by regulating fibroblast activation and matrix fibroblast
differentiation, whereas myofibroblast differentiation was largely PDGFRalpha
independent. These studies provide evidence for the phenotypic and functional
diversity as well as the extent of specificity of interstitial resident
fibroblasts differentiation during regeneration after partial pneumonectomy.
PMID- 26414961
TI - HIV-positive blood donors unaware of their sexual at-risk behaviours before
donation in Italy.
AB - BACKGROUND AND OBJECTIVES: Despite the procedures adopted for the selection of
blood donors, in Italy the HIV prevalence per 100 000 repeat tested donors (RTD)
and first-time tested donors (FTD) is high compared to most other Council of
Europe member states. To evaluate the effectiveness of predonation procedures, we
studied both the characteristics and the undisclosed risk behaviours of HIV
positive donors. MATERIALS AND METHODS: We analysed the data from the Italian
blood donor surveillance system in 2009, 2010 and 2011. Based on the postdonation
interview, HIV-positive donors were classified by risk behaviour (heterosexual,
MSM, 'non-sexual' and 'not determined') and by time elapsed from risk behaviour
to donation. In Italy, the temporary deferral for exposure to behaviour at risk
is 4 months. RESULTS: In the postdonation interview, 113 HIV-positive donors
(32.4%), who denied at-risk behaviours in the predonation selection, reported
sexual risk behaviours <4 months prior to donation; they were predominantly males
(84.1%) and RTD (63.7%). The main reason for not having reported the risk
behaviour in the predonation selection was 'not realizing having engaged in at
risk behaviour' (66.4%). CONCLUSION: These findings underline the need for more
comprehensible educational material, a clearer predonation questionnaire, and
effective information campaigns to improve the awareness of HIV sexual risk
behaviours among blood donors.
PMID- 26414962
TI - Increased Cardiovascular Mortality Risk in Women Discontinuing Postmenopausal
Hormone Therapy.
AB - CONTEXT: Current guidelines recommend annual discontinuation of postmenopausal
hormone therapy (HT) to evaluate whether a woman could manage without the
treatment. The impact of HT on cardiovascular health has been widely studied, but
it is not known how the withdrawal of HT affects cardiovascular risk. OBJECTIVE:
We evaluated the risk of cardiac or stroke death after the discontinuation of HT.
Design, Patients, Interventions, and Main Outcome Measures: Altogether 332 202
Finnish women discontinuing HT between 1994 and 2009 (data from National
Reimbursement register) were followed up from the discontinuation date to death
due to cardiac cause (n = 3177) or stroke (n = 1952), or to the end of 2009. The
deaths, retrieved from the national Cause of Death Register, were compared with
the expected number of deaths in the age-standardized background population. In a
subanalysis we also compared HT stoppers with HT users. RESULTS: Within the first
posttreatment year, the risk of cardiac death was significantly elevated
(standardized mortality ratio; 95% confidence interval 1.26; 1.16-1.37), whereas
follow-up for longer than 1 year was accompanied with a reduction (0.75; 0.72
0.78). The risk of stroke death in the first posttreatment year was increased
(1.63; 1.47-1.79), but follow-up for longer than 1 year was accompanied with a
reduced risk (0.89; 0.85-0.94). The cardiac (2.30; 2.12-2.50) and stroke (2.52;
2.28-2.77) death risk elevations were even higher when compared with HT users. In
women who discontinued HT at age younger than 60 years, but not in women aged 60
years or older, the cardiac mortality risk was elevated (1.94; 1.51-2.48).
CONCLUSIONS: Increased cardiovascular death risks question the safety of annual
HT discontinuation practice to evaluate whether a woman could manage without HT.
PMID- 26414964
TI - Preliminary Comparative Effectiveness of Robotic Versus Open Radical Cystectomy
in Elderly Patients.
AB - INTRODUCTION: Treatment for muscle-invasive bladder cancer (MIBC) remains highly
morbid despite improving surgical techniques. As the median age of diagnosis is
73, many patients are elderly at the time of cystectomy. We compare perioperative
surgical outcomes in elderly patients undergoing robotic vs open radical
cystectomy (RC). MATERIALS AND METHODS: Patients >75 years at time of RC were
identified. Demographic, clinicopathologic, and perioperative variables were
examined. Estimated blood loss (EBL) and length of stay (LOS) data were collected
with multivariate linear regression analysis performed to assess whether
technique was independently associated with outcomes. RESULTS: Eighty-seven
patients >75 years of age underwent cystectomy for MIBC (58 open, 29 robotic).
Mean age was 79.6 (+/-3.2) and 79.2 (+/-3.5) for open and robotic groups,
respectively (p = 0.64). There were no significant differences in baseline
comorbidities, clinical or pathologic stage, or use of neoadjuvant chemotherapy.
The mean number of lymph nodes removed was similar (p = 0.08). Robotic cystectomy
had significantly longer mean OR times (p < 0.001). On multivariate analyses,
robotic surgery was associated with -389cc less EBL (95% CI -547 to -230, p <
0.001) and a -1.5-day-shortened LOS (95%CI -2.9 to -0.2, p = 0.02) compared with
open surgery. There were no significant differences in surgical complications or
90-day readmission rates between the two groups. CONCLUSIONS: Robotic cystectomy
is safe and feasible in an elderly population. We observed longer OR times with
robotic surgery, but with decreased EBL, shorter hospital stays, and comparable
complication and readmission rates with open RC. Larger prospective studies are
required to confirm these findings.
PMID- 26414963
TI - Sex-Specific Differences in Hepatic Fat Oxidation and Synthesis May Explain the
Higher Propensity for NAFLD in Men.
AB - CONTEXT AND OBJECTIVE: In most populations a greater proportion of men have
hepatic steatosis than women. Sex-specific differences in hepatic dietary fatty
acid (FA) metabolism have not been well characterized. We compared fasting and
postprandial hepatic FA synthesis (de novo lipogenesis [DNL]) and oxidation in
men and women. PARTICIPANTS AND METHODS: Fasting and postprandial hepatic FA
metabolism was studied in 22 healthy men (n = 11) and women with similar age,
body mass index, and liver fat content using metabolic substrates labeled with
stable-isotope tracers ((2)H2O and [U(13)C]palmitate). Dietary FA oxidation was
assessed by appearance of (13)C into plasma 3-hydroxybutyrate and breath CO2 as
markers of liver and whole-body FA oxidation, respectively. RESULTS: Despite
similar liver fat content, fasting and postprandial plasma triacylglycerol (TG)
concentrations were significantly (P < .05) higher in men compared with women.
The appearance of (13)C from dietary FA into plasma 3-hydroxybutyrate and breath
CO2 was greater (P < .05) in women compared with men. Although the contribution
of DNL into very low-density lipoprotein (VLDL)-TG was similar (~ 10%) in the
fasting state, there was a divergence in pattern over the course of the study,
with men maintaining a higher contribution of DNL to VLDL-TG than women (P = .006
time x sex interaction). CONCLUSIONS: The combination of lower dietary FA
oxidation and a prolonged increase in DNL observed in men may represent
partitioning of FA into esterification and storage pathways within the liver,
leading to greater VLDL-TG production, and predispose to the sex difference in
hepatic steatosis.
PMID- 26414965
TI - MicroRNA 302/367 Cluster Effectively Facilitates Direct Reprogramming from Human
Fibroblasts into Functional Neurons.
AB - Recent studies suggest that mature somatic cells can be reprogrammed to become
induced pluripotent stem cells by overexpressing specific transcription factors
or microRNAs (miRNAs). Theoretically, this technique could provide a wide array
of cells for therapeutics. However, the process of redifferentiation after cell
reprogramming to pluripotency is inefficient and time restricted. We proposed
that the differentiation of somatic cells into specific cells of another germ
layer can be induced and accelerated with appropriate miRNAs and culture
conditions. In human fibroblasts, we found that overexpression of pluripotency
stem cell-specific miRNA-302/367 cluster, together with two other neuron-specific
miRNAs (miRNA-9/9* and miRNA-124) induced fibroblasts conversion into neurons.
The cells assumed neuron morphology, were positive for several neuron markers,
and exhibited neuronal membrane potential feature. Moreover, concentrated
expression of synaptic markers were observed in these cells in vitro and in vivo
in nude mice brain, suggesting possible connectivity. To achieve efficient
reprogramming, miRNA-302/367 cluster, miRNA-9/9*, and miRNA-124 were all
required. The combination of the proved pluripotency-inducing miRNA-302/367
cluster and cell-specific miRNAs provides a unique strategy for one-step cellular
conversion that could have important implications for studies of neuron
development and neurological disease therapy.
PMID- 26414966
TI - Pharmacoeconomics of long-acting atypical antipsychotics for acutely relapsed
chronic schizophrenia in Finland.
AB - BACKGROUND: Atypical long-acting injectable (LAI) antipsychotics are increasingly
available for treating chronic schizophrenia in patients chronically non-adherent
to prescribed regimens. Few economic studies have compared these products.
PURPOSE: To determine the cost-effectiveness of aripiprazole (ARI-LAI),
paliperidone (PP-LAI), olanzapine (OLZ-LAI), and risperidone (RIS-LAI) in
patients with chronic schizophrenia in Finland. METHODS: A 1-year decision tree
model was adapted with guidance from an expert panel. Patients started
hospitalized in relapse; those who responded continued treatment, others were
switched to secondary drugs, then clozapine in the event of 2nd line failure.
Rates of adherence, stable disease, relapse, and hospitalization were taken from
pivotal trials, and utilities from published research. Included were direct costs
paid by the Finnish Ministry of Health, in 2015 euros. Outcomes included quality
adjusted life-years (QALYs), hospitalization rates, and rates of relapse not
requiring hospitalization. Model robustness was assessed using a series of 1-way
and multivariate sensitivity analyses. RESULTS: Expected costs were lowest for PP
LAI at 41,148?, followed by 41,543? for ARI-LAI, 42,067? for RIS-LAI and 45,406?
for OLZ-LAI. Respective QALYs were 0.683, 0.671, 0.666, and 0.672. Re
hospitalization rates and non-admitted relapses were 23.6% and 3.9% for PP-LAI,
28.5% and 4.1% for ARI-LAI, 28.8% and 5.0% for RIS-LAI, 28.3% and 5.2% for OLZ
LAI. PP-LAI treatment was associated with the most days with stable disease
(132.0), followed by OLZ-LAI (125.5), ARI-LAI (122.6), and RIS-LAI (114.4).
Sensitive inputs between PP-LAI and ARI-LAI included rates of adherence,
dropouts, and relapses plus drug prices; dropout and relapse rates for RIS-LAI;
OLZ-LAI results were insensitive. In probability sensitivity analyses, PP-LAI
dominated ARI-LAI in 75.8% of the 10,000 iterations, RIS-LAI in 83.1% and OLZ-LAI
in 95.7%. CONCLUSIONS: PP-LAI dominated the other atypicals. It appears to be the
preferred option for treating chronic relapsing schizophrenia.
PMID- 26414967
TI - Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice
Advice From the Clinical Guidelines Committee of the American College of
Physicians.
AB - DESCRIPTION: Pulmonary embolism (PE) can be a severe disease and is difficult to
diagnose, given its nonspecific signs and symptoms. Because of this, testing
patients with suspected acute PE has increased dramatically. However, the overuse
of some tests, particularly computed tomography (CT) and plasma d-dimer
measurement, may not improve care while potentially leading to patient harm and
unnecessary expense. METHODS: The literature search encompassed studies indexed
by MEDLINE (1966-2014; English-language only) and included all clinical trials
and meta-analyses on diagnostic strategies, decision rules, laboratory tests, and
imaging studies for the diagnosis of PE. This document is not based on a formal
systematic review, but instead seeks to provide practical advice based on the
best available evidence and recent guidelines. The target audience for this paper
is all clinicians; the target patient population is all adults, both inpatient
and outpatient, suspected of having acute PE. BEST PRACTICE ADVICE 1: Clinicians
should use validated clinical prediction rules to estimate pretest probability in
patients in whom acute PE is being considered. BEST PRACTICE ADVICE 2: Clinicians
should not obtain d-dimer measurements or imaging studies in patients with a low
pretest probability of PE and who meet all Pulmonary Embolism Rule-Out Criteria.
BEST PRACTICE ADVICE 3: Clinicians should obtain a high-sensitivity d-dimer
measurement as the initial diagnostic test in patients who have an intermediate
pretest probability of PE or in patients with low pretest probability of PE who
do not meet all Pulmonary Embolism Rule-Out Criteria. Clinicians should not use
imaging studies as the initial test in patients who have a low or intermediate
pretest probability of PE. BEST PRACTICE ADVICE 4: Clinicians should use age
adjusted d-dimer thresholds (age * 10 ng/mL rather than a generic 500 ng/mL) in
patients older than 50 years to determine whether imaging is warranted. BEST
PRACTICE ADVICE 5: Clinicians should not obtain any imaging studies in patients
with a d-dimer level below the age-adjusted cutoff. BEST PRACTICE ADVICE 6:
Clinicians should obtain imaging with CT pulmonary angiography (CTPA) in patients
with high pretest probability of PE. Clinicians should reserve ventilation
perfusion scans for patients who have a contraindication to CTPA or if CTPA is
not available. Clinicians should not obtain a d-dimer measurement in patients
with a high pretest probability of PE.
PMID- 26414969
TI - Spironolactone for resistant hypertension--hard to resist?
PMID- 26414968
TI - Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal
treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double
blind, crossover trial.
AB - BACKGROUND: Optimal drug treatment for patients with resistant hypertension is
undefined. We aimed to test the hypotheses that resistant hypertension is most
often caused by excessive sodium retention, and that spironolactone would
therefore be superior to non-diuretic add-on drugs at lowering blood pressure.
METHODS: In this double-blind, placebo-controlled, crossover trial, we enrolled
patients aged 18-79 years with seated clinic systolic blood pressure 140 mm Hg or
greater (or >=135 mm Hg for patients with diabetes) and home systolic blood
pressure (18 readings over 4 days) 130 mm Hg or greater, despite treatment for at
least 3 months with maximally tolerated doses of three drugs, from 12 secondary
and two primary care sites in the UK. Patients rotated, in a preassigned,
randomised order, through 12 weeks of once daily treatment with each of
spironolactone (25-50 mg), bisoprolol (5-10 mg), doxazosin modified release (4-8
mg), and placebo, in addition to their baseline blood pressure drugs. Random
assignment was done via a central computer system. Investigators and patients
were masked to the identity of drugs, and to their sequence allocation. The dose
was doubled after 6 weeks of each cycle. The hierarchical primary endpoints were
the difference in averaged home systolic blood pressure between spironolactone
and placebo, followed (if significant) by the difference in home systolic blood
pressure between spironolactone and the average of the other two active drugs,
followed by the difference in home systolic blood pressure between spironolactone
and each of the other two drugs. Analysis was by intention to treat. The trial is
registered with EudraCT number 2008-007149-30, and ClinicalTrials.gov number,
NCT02369081. FINDINGS: Between May 15, 2009, and July 8, 2014, we screened 436
patients, of whom 335 were randomly assigned. After 21 were excluded, 285
patients received spironolactone, 282 doxazosin, 285 bisoprolol, and 274 placebo;
230 patients completed all treatment cycles. The average reduction in home
systolic blood pressure by spironolactone was superior to placebo (-8.70 mm Hg
[95% CI -9.72 to -7.69]; p<0.0001), superior to the mean of the other two active
treatments (doxazosin and bisoprolol; -4.26 [-5.13 to -3.38]; p<0.0001), and
superior when compared with the individual treatments; versus doxazosin (-4.03 [
5.04 to -3.02]; p<0.0001) and versus bisoprolol (-4.48 [-5.50 to -3.46];
p<0.0001). Spironolactone was the most effective blood pressure-lowering
treatment, throughout the distribution of baseline plasma renin; but its margin
of superiority and likelihood of being the best drug for the individual patient
were many-fold greater in the lower than higher ends of the distribution. All
treatments were well tolerated. In six of the 285 patients who received
spironolactone, serum potassium exceeded 6.0 mmol/L on one occasion.
INTERPRETATION: Spironolactone was the most effective add-on drug for the
treatment of resistant hypertension. The superiority of spironolactone supports a
primary role of sodium retention in this condition. FUNDING: The British Heart
Foundation and National Institute for Health Research.
PMID- 26414970
TI - Left-Sided Flank Pain, Fevers, and Fatigue in a 26-Year-Old Male With
Seropositive Rheumatoid Arthritis.
PMID- 26414971
TI - Hospice Diagnosis: Polypharmacy: A Teachable Moment.
PMID- 26414972
TI - Treatment of prosthetic joint infections due to Propionibacterium. Similar
results in 60 patients treated with and without rifampicin.
AB - BACKGROUND AND PURPOSE: Currently, Propionibacterium is frequently recognized as
a causative microorganism of prosthetic joint infection (PJI). We assessed
treatment success at 1- and 2-year follow-up after treatment of Propionibacterium
associated PJI of the shoulder, hip, and knee. Furthermore, we attempted to
determine whether postoperative treatment with rifampicin is favorable. PATIENTS
AND METHODS: We conducted a retrospective cohort study in which we included
patients with a primary or revision joint arthroplasty of the shoulder, hip, or
knee who were diagnosed with a Propionibacterium-associated PJI between November
2008 and February 2013 and who had been followed up for at least 1 year. RESULTS:
We identified 60 patients with a Propionibacterium-associated PJI with a median
duration of 21 (0.1-49) months until the occurrence of treatment failure. 39
patients received rifampicin combination therapy, with a success rate of 93% (95%
CI: 83-97) after 1 year and 86% (CI: 71-93) after 2 years. The success rate was
similar in patients who were treated with rifampicin and those who were not.
INTERPRETATION: Propionibacterium-associated PJI treated with surgery in
combination with long-term antibiotic administration had a successful outcome at
1- and 2-year follow-up irrespective of whether the patient was treated with
rifampicin. Prospective studies are needed to determine whether the use of
rifampicin is beneficial in the treatment of Propionibacterium-associated PJI.
PMID- 26414973
TI - Effect of Melatonin on Sleep in the Perioperative Period after Breast Cancer
Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.
AB - STUDY OBJECTIVES: To investigate whether administration of an oral dose of 6 mg
melatonin before bedtime perioperatively in breast cancer surgery could change
sleep outcomes measured by actigraphy. METHODS: This paper reports secondary
outcomes from a double-blind, placebo-controlled, randomized clinical trial where
patients received 6 mg melatonin (n = 27) or placebo (n = 21) approximately 60
minutes before bedtime 3 nights preoperatively until at least one week
postoperatively. Participants were monitored in the entire period with
actigraphy, and were instructed to complete visual analogue scale (VAS) for
sleep, and the Karolinska Sleepiness Scale (KSS) each morning. RESULTS:
Administration of 6 mg oral melatonin approximately 1 hour before bedtime
resulted in significantly increased sleep efficiency and reduced wake after sleep
onset for the entire 2-week postoperative period. No other significant
differences for actigraphy determined sleep outcomes or subjective outcome
parameters in the perioperative period were found between the groups. Overall,
the patients sleep outcomes were within normal ranges and no participants had
pathological sleep disturbances. CONCLUSIONS: Melatonin significantly changed
sleep efficiency and wake after sleep onset after surgery, but had no effects on
other objective sleep outcomes or on subjective sleep quality (VAS and KSS).
PMID- 26414974
TI - Improvement of Cognitive and Psychomotor Performance in Patients with Mild to
Moderate Obstructive Sleep Apnea Treated with Mandibular Advancement Device: A
Prospective 1-Year Study.
AB - STUDY OBJECTIVES: This study aimed to provide the evidence on effect of
mandibular advancement device (MAD) therapy on long-term cognitive and
psychomotor performance, excessive daytime sleepiness, and quality of life in
patients with mild to moderate obstructive sleep apnea (OSA). METHODS: A total of
15 patients with mild to moderate OSA were treated with MAD therapy and they were
followed up after 3 mo and 1 y of therapy. The patients were tested on three
different tests of cognitive and psychomotor performance using the computer-based
system Complex Reactionmeter Drenovac (CRD-series) at baseline and at the time of
follow-up, and the 36-Item Short Form Health Survey (SF-36) questionnaire and
Epworth Sleepiness Scale were used to assess their quality of life and excessive
daytime sleepiness, respectively. RESULTS: The mean apnea-hypopnea index (AHI)
decreased significantly from 22.9 +/- 5.9 events/h at baseline, to 9.7 +/- 4.5
events/h after 1 y of MAD therapy (p < 0.001). There was significant improvement
on all three CRD-series tests used after 1 y of MAD therapy, considering total
test solving time (TTST) and minimal single task solving time (MinT), whereas
total number of errors committed during the tests (TE) remained unchanged. Self
reported measures, excessive daytime sleepiness, and three domains of quality of
life, social functioning, general health perception, and health change following
MAD therapy showed significant improvements after 1 y of MAD therapy.
CONCLUSIONS: This study demonstrates significant improvements in cognitive and
psychomotor performance, particularly in the domain of perceptive abilities,
convergent thinking (constructing and solving simple mathematical tasks) and
psychomotor reaction times, excessive daytime sleepiness, and quality of life in
patients with mild to moderate OSA following MAD therapy.
PMID- 26414975
TI - Effects of Blast Exposure on Subjective and Objective Sleep Measures in Combat
Veterans with and without PTSD.
AB - STUDY OBJECTIVES: This study examined the extent to which self-reported exposure
to blast during deployment to Iraq and Afghanistan affects subjective and
objective sleep measures in service members and veterans with and without
posttraumatic stress disorder (PTSD). METHODS: Seventy-one medication-free
service members and veterans (mean age = 29.47 +/- 5.76 years old; 85% men)
completed self-report sleep measures and overnight polysomnographic studies. Four
multivariate analyses of variance (MANOVAs) were conducted to examine the impact
of blast exposure and PTSD on subjective sleep measures, measures of sleep
continuity, non-rapid eye movement (NREM) sleep parameters, and rapid eye
movement (REM) sleep parameters. RESULTS: There was no significant Blast * PTSD
interaction on subjective sleep measures. Rather, PTSD had a main effect on
insomnia severity, sleep quality, and disruptive nocturnal behaviors. There was
no significant Blast * PTSD interaction, nor were there main effects of PTSD or
Blast on measures of sleep continuity and NREM sleep. A significant PTSD * Blast
interaction effect was found for REM fragmentation. CONCLUSIONS: The results
suggest that, although persistent concussive symptoms following blast exposure
are associated with sleep disturbances, self-reported blast exposure without
concurrent symptoms does not appear to contribute to poor sleep quality,
insomnia, and disruptive nocturnal disturbances beyond the effects of PTSD.
Reduced REM sleep fragmentation may be a sensitive index of the synergetic
effects of both psychological and physical insults.
PMID- 26414976
TI - Measuring Treatment Outcomes in Comorbid Insomnia and Fibromyalgia: Concordance
of Subjective and Objective Assessments.
AB - STUDY OBJECTIVES: In insomnia, actigraphy tends to underestimate wake time
compared to diaries and PSG. When chronic pain co-occurs with insomnia, sleep may
be more fragmented, including more movement and arousals. However, individuals
may not be consciously aware of these arousals. We examined the baseline
concordance of diaries, actigraphy, and PSG as well as the ability of each
assessment method to detect changes in sleep following cognitive behavioral
therapy for insomnia (CBT-I). METHODS: Adults with insomnia and fibromyalgia (n =
113) were randomized to CBT-I, CBT for pain, or waitlist control. At baseline and
posttreatment, participants completed one night of PSG and two weeks of
diaries/actigraphy. RESULTS: At baseline, objective measures estimated lower SOL,
higher TST, and higher SE than diaries (ps < 0.05). Compared to PSG, actigraphic
estimates were higher for SOL and lower for WASO (ps < 0.05). Repeated measures
ANOVAs were conducted for the CBT-I group (n = 15), and significant method by
time interactions indicated that the assessment methods differed in their
sensitivity to detect treatment-related changes. PSG values did not change
significantly for any sleep parameters. However, diaries showed improvements in
SOL, WASO, and SE, and actigraphy also detected the WASO and SE improvements (ps
< 0.05). CONCLUSIONS: Actigraphy was generally more concordant with PSG than with
diaries, which are the recommended assessment for diagnosing insomnia. However,
actigraphy showed greater sensitivity to treatment-related changes than PSG; PSG
failed to detect any improvements, but actigraphy demonstrated changes in WASO
and SE, which were also found with diaries. In comorbid insomnia/fibromyalgia,
actigraphy may therefore have utility in measuring treatment outcomes.
PMID- 26414977
TI - Derived Arterial Stiffness is Increased in Patients with Obstructive Sleep Apnea
and Periodic Limb Movements during Sleep.
AB - STUDY OBJECTIVES: Both periodic limb movements during sleep (PLMS) and
obstructive sleep apnea (OSA) have been associated with increased risk of
cardiovascular disease (CVD). OSA has also been linked to increased large
arterial stiffness, which is considered an independent risk factor for CVD. We
utilized a previously validated index of large artery stiffness (SIDVP) derived
from the digital volume pulse (DVP) to seek comparison in patients with PLMS and
OSA. METHODS: Forty-nine adult male subjects, without known comorbidities that
could affect arterial stiffness or on vasoactive medication, were retrospectively
identified and categorized into controls (n = 8), PLMS (n = 13), OSA (n = 17),
and OSA/PLMS (n = 11). The cutoff for PLMS was a periodic limb movement index
(PLMI) > 15 events/h, and for OSA an apnea-hypopnea index (AHI) > 10 events/h.
SIDVP was derived from the raw data of photoplethysmography of the nocturnal
polysomnography, averaged for 2 min prior to sleep study initiation (baseline),
after completion in the morning, and every half hour after sleep onset. RESULTS:
The groups were age/body mass index-matched. Controls showed lower baseline,
morning, and overall SIDVP compared to the other groups (p < 0.01). Patients with
PLMS (PLMI: 50.69 +/- 9.7 events/h) and the OSA group (AHI: 29.7 +/- 2 events/h)
demonstrated similar overall SIDVP (6.78 +/- 0.08 versus 6.94 +/- 0.04,
respectively, p = 0.5), whereas the OSA/PLMS (AHI: 29.35 +/- 8, PLMI: 50.63 +/-
7.2) group demonstrated the highest (7.40 +/- 0.06, p < 0.001). CONCLUSIONS:
Based on an easily reproducible and applicable marker of large arterial
stiffness, patients with significant PLMS had higher SIDVP when compared to
controls and comparable to those with moderate/severe OSA. The OSA/PLMS group had
the highest SIDVP, implying a possible additive effect of OSA and PLMS on
arterial stiffness.
PMID- 26414979
TI - Expiratory Time Constant and Sleep Apnea Severity in the Overlap Syndrome.
AB - STUDY OBJECTIVES: Lung mechanics in the overlap of COPD and sleep apnea impact
the severity of sleep apnea. Specifically, increased lung compliance with
hyperinflation protects against sleep apnea, whereas increased airway resistance
worsens sleep apnea. We sought to assess whether the expiratory time constant,
which reflects lung mechanics, is associated with sleep apnea severity in such
patients. METHODS: Polysomnographies in 34 subjects with the overlap syndrome
were reviewed. Three time constants were measured for each of up to 5 stages
(wake, NREM stages, and REM). The time constants were derived by fitting time and
pressure coordinates on the expiratory portion of a nasal pressure signal along
an exponentially decaying equation, and solving for the time constant.
Demographics, morphometrics, wake end-tidal CO2, right diaphragmatic arc on a
chest radiograph, and the apnea-hypopnea index (AHI) were recorded. RESULTS: The
time constant was not associated with age, gender, body mass index, right
diaphragmatic arc, or wake end-tidal CO2, and was not significantly different
between sleep stages. A mean time constant (TC) was therefore obtained. Subjects
with a TC > 0.5 seconds had a greater AHI than those with a TC <= 0.5 seconds
(median AHI 58 vs. 18, respectively, p = 0.003; Odds ratio of severe sleep apnea
10.6, 95% CI 3.9-51.1, p = 0.005). CONCLUSIONS: A larger time constant in the
overlap syndrome is associated with increased odds of severe sleep apnea,
suggesting a greater importance of airway resistance relative to lung compliance
in sleep apnea causation in these subjects.
PMID- 26414980
TI - Mandibular Advancement Device-Emergent Central Sleep Apnea Can Resolve
Spontaneously: A Case Report.
AB - ABSTRACT: The development of treatment emergent central sleep apnea (CSA) has
been described after almost all obstructive sleep apnea (OSA) therapies. While
the course of positive airway pressure (PAP) emergent CSA, is better established;
little is known about the natural course of mandibular advancement device (MAD)
emergent CSA. Previous reports failed to comment on its natural course or report
treatment with advanced ventilator modes such as adaptive servoventilation. We
describe spontaneous resolution of MAD emergent CSA in a patient with moderate
OSA who refused PAP. We also highlight the need for follow up polysomnography
(PSG) after maximal advancement with a MAD and the possible association between
MAD emergent CSA and atrial fibrillation. The exact pathophysiology of this
phenomenon remains unclear but may relate to high loop gain of the respiratory
system resulting in ventilatory overshoot after treatment and atrial fibrillation
associated increased susceptibility to periodic ventilation.
PMID- 26414978
TI - Influence of Day Length and Physical Activity on Sleep Patterns in Older
Icelandic Men and Women.
AB - STUDY OBJECTIVES: To identify cross-sectional and seasonal patterns of sleep and
physical activity (PA) in community-dwelling, older Icelandic adults using
accelerometers. METHODS: A seven-day free-living protocol of 244 (110 female)
adults aged 79.7 +/- 4.9 years was conducted as part of a larger population-based
longitudinal observational-cohort study in the greater Reykjavik area of Iceland.
A subpopulation (n = 72) repeated the 7-day measurement during seasonal periods
with greater (13.4 +/- 1.4 h) and lesser (7.7 +/- 1.8 h) daylight. RESULTS: Cross
sectional analyses using multiple linear regression models revealed that day
length was a significant independent predictor of sleep duration, mid-sleep, and
rise time (all p < 0.05). However, the actual within-individual differences in
sleep patterns of the repeaters were rather subtle between periods of longer and
shorter day-lengths. Compared to women, men had a shorter sleep duration (462 +/-
80 vs. 487 +/- 68 minutes, p = 0.008), earlier rise time, and a greater number of
awakenings per night (46.5 +/- 18.3 vs. 40.2 +/- 15.7, p = 0.007), but sleep
efficiency and onset latency were similar between the two sexes. Daily PA was
also similar between men and women and between periods of longer and shorter day
lengths. BMI, age, gender, and overall PA all contributed to the variations in
sleep parameters using multiple regression analysis. CONCLUSIONS: The sleep and
PA characteristics of this unique population revealed some gender differences,
but there was limited variation in response to significant daylight changes which
may be due to long-term adaptation.
PMID- 26414981
TI - Does Increased IGF-1 Concentration Have a Clear Positive Significance in Reducing
Depression and Posttraumatic Arousal Symptoms?
PMID- 26414982
TI - Changes in Vitamin D Status after Nasal Continuous Positive Airway Pressure:
Could Alterations in Systemic Inflammatory Markers Explain These Observations?
PMID- 26414984
TI - Do Evidence-Based Treatments for Circadian Rhythm Sleep-Wake Disorders Make the
GRADE? Updated Guidelines Point to Need for More Clinical Research.
PMID- 26414983
TI - American Academy of Sleep Medicine (AASM) Position Paper for the Use of
Telemedicine for the Diagnosis and Treatment of Sleep Disorders.
AB - The American Academy of Sleep Medicine's (AASM) Taskforce on Sleep Telemedicine
supports telemedicine as a means of advancing patient health by improving access
to the expertise of Board-Certified Sleep Medicine Specialists. However, such
access improvement needs to be anchored in attention to quality and value in
diagnosing and treating sleep disorders. Telemedicine is also useful to promote
professionalism through patient care coordination and communication between other
specialties and sleep medicine. Many of the principles and key concepts adopted
here are based on U.S. industry standards, with special consideration given to
the body of work by the American Telemedicine Association
(http://www.americantelemed.org/), and abide by standards endorsed by the
American Medical Association (http://www.ama-assn.org/). Practitioners who wish
to integrate sleep telemedicine into their practice should have a clear
understanding of the salient issues, key terminology, and the following
recommendations from the AASM. The Taskforce recommends the following: * Clinical
care standards for telemedicine services should mirror those of live office
visits, including all aspects of diagnosis and treatment decisions as would be
reasonably expected in traditional office-based encounters. * Clinical judgment
should be exercised when determining the scope and extent of telemedicine
applications in the diagnosis and treatment of specific patients and sleep
disorders. * Live Interactive Telemedicine for sleep disorders, if utilized in a
manner consistent with the principles outlined in this document, should be
recognized and reimbursed in a manner competitive or comparable with traditional
in-person visits. * Roles, expectations, and responsibilities of providers
involved in the delivery of sleep telemedicine should be defined, including those
at originating sites and distant sites. * The practice of telemedicine should aim
to promote a care model in which sleep specialists, patients, primary care
providers, and other members of the healthcare team aim to improve the value of
healthcare delivery in a coordinated fashion. * Appropriate technical standards
should be upheld throughout the telemedicine care delivery process, at both the
originating and distant sites, and specifically meet the standards set forth by
the Health Insurance Portability and Accountability Act (HIPAA). * Methods that
aim to improve the utility of telemedicine exist and should be explored,
including the utilization of patient presenters, local resources and providers,
adjunct testing, and add-on technologies. * Quality Assurance processes should be
in place for telemedicine care delivery models that aim to capture process
measures, patient outcomes, and patient/provider experiences with the model(s)
employed. * Time for data management, quality processes, and other aspects of
care delivery related to telemedicine encounters should be recognized in value
based care delivery models. * The use of telemedicine services and its equipment
should adhere to strict professional and ethical standards so as not to violate
the intent of the telemedicine interaction while aiming to improve overall
patient access, quality, and/or value of care. * When billing for telemedicine
services, it is recommended that patients, providers, and others rendering
services understand payor reimbursements, and that there be financial
transparency throughout the process. * Telemedicine utilization for sleep
medicine is likely to rapidly expand, as are broader telehealth applications in
general; further research into the impact and outcomes of these are needed. This
document serves as a resource by defining issues and terminology and explaining
recommendations. However, it is not intended to supersede regulatory or
credentialing recommendations and guidelines. It is intended to support and be
consistent with professional and ethical standards of the profession.
PMID- 26414985
TI - In Memoriam: Arthur J. Spielman, PhD 1947-2015.
PMID- 26414988
TI - AASM Young Investigators Research Forum Helps Ensure a Bright Future for Sleep
and Circadian Research.
PMID- 26414987
TI - Effect of Acute Sleep Disturbance and Recovery on Insulin-Like Growth Factor-1
(IGF-1): Possible Connections and Clinical Implications.
PMID- 26414989
TI - Confronting Drowsy Driving: The American Academy of Sleep Medicine Perspective.
AB - ABSTRACT: Drowsy driving is a serious public health concern which is often
difficult for individual drivers to identify. While it is important for drivers
to understand the causes of drowsy driving, there is still insufficient
scientific knowledge and public education to prevent drowsy driving. As a result,
the AASM is calling upon institutions and policy makers to increase public
awareness and improve education on the issue, so our society can better recognize
and prevent drowsy driving. The AASM has adopted a position statement to educate
both healthcare providers and the general public about drowsy driving risks and
countermeasures.
PMID- 26414986
TI - Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep
Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake
Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and
Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015: An American
Academy of Sleep Medicine Clinical Practice Guideline.
AB - A systematic literature review and meta-analyses (where appropriate) were
performed and the GRADE approach was used to update the previous American Academy
of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian
rhythm sleep-wake disorders. Available data allowed for positive endorsement (at
a second-tier degree of confidence) of strategically timed melatonin (for the
treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with
ISWRD and comorbid neurological disorders), and light therapy with or without
accompanying behavioral interventions (adults with ASWPD, children/adolescents
with DSWPD, and elderly with dementia). Recommendations against the use of
melatonin and discrete sleep-promoting medications are provided for demented
elderly patients, at a second- and first-tier degree of confidence, respectively.
No recommendations were provided for remaining treatments/ populations, due to
either insufficient or absent data. Areas where further research is needed are
discussed.
PMID- 26414991
TI - Postoperative Complications in Patients with Obstructive Sleep Apnea: Where Do We
Stand?
PMID- 26414992
TI - sigma-Aromaticity in polyhydride complexes of Ru, Ir, Os, and Pt.
AB - Transition-metal hydrides represent a unique class of compounds, which are
essential for catalysis, organic synthesis, and hydrogen storage. In this work we
study IrH5(PPh3)2, (RuH5(P(i)Pr3)2)(-), (OsH5(P(i)Pr3)2)(-), and OsH4(PPhMe2)3
polyhydride complexes, inspired by the recent discovery of the sigma-aromatic
PtZnH5(-) cluster anion. The distinctive feature of these molecules is that, like
in the PtZnH5(-) cluster, the metal is five-fold coordinated in-plane, and holds
additional ligands at the axial positions. This work shows that the unusual
coordination in these compounds indeed can be explained by sigma-aromaticity in
the pentagonal arrangement, stabilized by the atomic orbitals on the metal. Based
on this newly elucidated bonding principle, we additionally propose a new family
of polyhydrides that display a uniquely high coordination. We also report the
first indications of how aromaticity may impact the reactivity of these
molecules.
PMID- 26414990
TI - The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia: A Randomized,
Double-Blind, Placebo-Controlled, Two-Way Crossover Study.
AB - OBJECTIVE: This study examined the effects of milnacipran on polysomnographic
(PSG) measures of sleep and subjective complaints in patients with fibromyalgia
and disturbed sleep. METHODS: This was a single-site, double-blind, placebo
controlled, two-period crossover PSG study. Eligible subjects (aged 28-72 y) were
randomized (1:1) to milnacipran (100 mg/d) or placebo for crossover period 1, and
vice versa for period 2. Each crossover period comprised a dose-escalation and
dose-maintenance phase, with a 2-w taper/washout between periods. In-laboratory
PSGs were collected at baseline, and at the end of each treatment period. The
primary endpoints were the difference in PSG-recorded wake after sleep onset
(WASO), number of awakenings after sleep onset (NAASO), and sleep efficiency (SE)
between 4 w of maintenance treatment with milnacipran and placebo. Other PSG
measures, subject-rated sleep, fatigue, physical functioning, and pain were
assessed. Post hoc analysis was performed in subjects showing at least 25%
reduction in pain from baseline in the Brief Pain Inventory Score (responders).
RESULTS: Of 19 subjects randomized, 15 completed both periods. Subjects treated
with milnacipran showed no significant improvements in WASO and NAASO, but showed
reduced SE (p = 0.049). Milnacipran did not show significant improvement in other
PSG parameters or subjective endpoints. Two thirds of completers met responder
criteria and additionally showed a significant improvement in daily effect of
pain (p = 0.043) and subjective sleep quality (p = 0.040). CONCLUSION: The data
suggest that milnacipran is not sedating in most patients with fibromyalgia and
improvements in sleep are likely a result of pain improvement. CLINICAL TRIAL
REGISTRATION: ClinicalTrials.gov, identifier: NCT01234675.
PMID- 26414993
TI - A Sustainable Multicomponent Pyrimidine Synthesis.
AB - Since alcohols are accessible from indigestible biomass (lignocellulose), the
development of novel preferentially catalytic reactions in which alcohols are
converted into important classes of fine chemicals is a central topic of
sustainable synthesis. Multicomponent reactions are especially attractive in
organic chemistry as they allow the synthesis of large libraries of diversely
functionalized products in a short time when run in a combinatorial fashion.
Herein, we report a novel, regioselective, iridium-catalyzed multicomponent
synthesis of pyrimidines from amidines and up to three (different) alcohols. This
reaction proceeds via a sequence of condensation and dehydrogenation steps which
give rise to selective C-C and C-N bond formations. While the condensation steps
deoxygenate the alcohol components, the dehydrogenations lead to aromatization.
Two equiv of hydrogen and water are liberated in the course of the reactions.
PN5P-Ir-pincer complexes, recently developed in our laboratory, catalyze this
sustainable multicomponent process most efficiently. A total of 38 different
pyrimidines were synthesized in isolated yields of up to 93%. Strong points of
the new protocol are its regioselectivity and thus the immediate access to
pyrimidines that are highly and unsymmetrically decorated with alkyl or aryl
substituents. The combination of this novel protocol with established methods for
converting alcohols to nitriles now allows to selectively assemble pyrimidines
from four alcohol building blocks and 2 equiv of ammonia.
PMID- 26414994
TI - Measures of Quality of Care for People with HIV: A Scoping Review of Performance
Indicators for Primary Care.
AB - The healthcare of people with HIV is transitioning from specialty care to the
primary healthcare (PHC) system. However, many of the performance indicators used
to measure the quality of HIV care pre-date this transition. The goal of this
work was to examine how existing HIV care performance indicators measure the
comprehensive and longitudinal care offered in a PHC setting. A scoping review
consisting of peer-reviewed and grey literature searches was performed. Two
reviewers evaluated study eligibility and indicators in documents meeting
inclusion criteria were extracted into a database. Indicators were matched to a
PHC performance measurement framework to determine their applicability for
evaluating quality of care in the PHC setting. The literature search identified
221 publications, of which 47 met inclusion criteria. 1184 indicators were
extracted and removal of duplicates left 558 unique indicators. A majority of the
558 indicators fell under the 'secondary prevention' (12%) and 'care of chronic
conditions' (33%) domains when indicators were matched to the PHC performance
framework. Despite the imbalance, nearly all performance domains in the PHC
framework were populated by at least one indicator with significant
concentrations in domains such as patient-provider relationship, patient
satisfaction, population and community characteristics, and access to care.
Existing performance frameworks for the care of people with HIV provide a
comprehensive set of indicators that align well with a PHC performance framework.
Nonetheless, some important elements of care, such as patient-reported outcomes,
are poorly covered by existing indicators. Advancing our understanding of how the
experience of care for people with HIV is impacted by changes in health services
delivery, specifically more care within the PHC system, will require performance
indicators to capture this aspect of HIV care.
PMID- 26414995
TI - DAZL Expression Explains Origin and Central Formation of Primordial Germ Cells in
Chickens.
AB - The timing and biological events associated with germ cell specification in
chickens have not been determined yet. In this study, we report the origin of
primordial germ cells (PGCs) and germ plasm dynamics through investigation of the
expression of the chicken homolog of deleted in azoospermia-like (cDAZL) gene
during germ cell specification. Asymmetric localization of germ plasm in the
center of oocytes from preovulatory follicle stages leads to PGCs being formed in
the center. During cleavage stages, DAZL expression pattern changes from a
subcellular localization to a diffuse form before and after zygotic genome
activation. Meanwhile, PGCs exhibit transcriptional active status during their
specification. In addition, knockdown studies of cDAZL, which result in reduced
proliferation, aberrant gene expression profiles, and PGC apoptosis in vitro,
suggest its possible roles for PGC formation in chicken. In conclusion, DAZL
expression reveals formation and initial positioning of PGCs in chickens.
PMID- 26414996
TI - Relationship between circadian rhythm amplitude and stability with sleep quality
and sleepiness among shift nurses and health care workers.
AB - INTRODUCTION: Sleep is affected by the circadian cycle and its features.
Amplitude and stability of circadian rhythm are important parameters of the
circadian cycle. This study aims to examine the relationship between amplitude
and stability of circadian rhythm with sleep quality and sleepiness. METHOD: In
this cross-sectional research, 315 shift nurses and health care workers from
educational hospitals of Kerman University of Medical Sciences (KUMS), Iran, were
selected using a random sampling method. The Pittsburgh Sleep Quality Index
(PSQI), Epworth Sleepiness Scale (ESS) and Circadian Type Inventory (CTI) were
used to collect the required data. RESULTS: In this study, 83.2% suffered from
poor sleep and one-half had moderate and excessive sleepiness. The results showed
that flexibility in circadian rhythm stability, job stress and sleepiness are
among the factors affecting quality sleep in shift workers. DISCUSSION: Those
whose circadian rhythm amplitude was languid suffered more from sleepiness and
those whose circadian stability was flexible had a better sleep. Variables
including circadian rhythm stability (flexible/rigid) and amplitude
(languid/vigorous) can act as predictive indices in order to employ people in a
shift work system so that sleepiness and a drop in quality of sleep are
prevented.
PMID- 26414997
TI - Analytical Ultracentrifugation as an Approach to Characterize Recombinant Adeno
Associated Viral Vectors.
AB - Recombinant adeno-associated viral (rAAV) vectors represent a novel class of
biopharmaceutical drugs. The production of clinical-grade rAAV vectors for gene
therapy would benefit from analytical methods that are able to monitor drug
product quality with regard to homogeneity, purity, and manufacturing
consistency. Here, we demonstrate the novel application of analytical
ultracentrifugation (AUC) to characterize the homogeneity of preparations of rAAV
vectors. We show that a single sedimentation velocity run of rAAV vectors
detected and quantified a number of different viral species, such as vectors
harboring an intact genome, lacking a vector genome (empty particles), and
containing fragmented or incomplete vector genomes. This information is obtained
by direct boundary modeling of the AUC data generated from refractometric or UV
detection systems using the computer program SEDFIT. Using AUC, we show that
multiple parameters contributed to vector quality, including the AAV genome form
(i.e., self-complementary vs. single-stranded), vector genome size, and the
production and purification methods. Hence, AUC is a critical tool for
identifying optimal production and purification processes and for monitoring the
physical attributes of rAAV vectors to ensure their quality.
PMID- 26414998
TI - Therapeutic ultrasound stimulates MC3T3-E1 cell proliferation through the
activation of NF-kappaB1, p38alpha, and mTOR.
AB - BACKGROUND AND OBJECTIVES: As the population ages, osteometabolic diseases and
osteoporotic fractures emerge, resulting in substantial healthcare resource
utilization and impaired quality of life. Many types of mechanical stimulation
have the potential of being recognized by bone cells after a mechanical sign is
transformed into a biological one (a process called mechanotransduction). The
therapeutic ultrasound (TU) is one of several resources capable of promoting bone
cell mechanical stimulation. Therefore, the main purpose of present study was to
evaluate the effect of TU on the proliferation of pre-osteoblasts using in vitro
bioassays. STUDY DESIGN/MATERIALS AND METHODS: We used MC3T3-E1 pre-osteoblast
lineage cells kept in Alpha medium. Cells were treated using pulsed mode
therapeutic ultrasound, with frequency of 1 MHz, intensity of 0.2 W/cm(2) (SATA),
duty cycle of 20%, for 30 minutes. Nifedipine and rapamycin were used to further
investigate the role of L-type Ca(2+) channels and mTOR pathway. Intracellular
calcium, TGF-beta1, magnesium, and the mRNA levels of osteopontin, osteonectin,
NF-kappaB1, p38alpha were evaluated. RESULTS: The results show that TU stimulates
the growth of MC3T3-E1 cells and decreases the supernatant calcium and magnesium
content. Also, it increases intracellular calcium, activates NF-kappaB1 and mTOR
complex via p38alpha. Moreover, TU promoted a decrease in the TGF-beta1
synthesis, which is a cell growth inhibitor. CONCLUSIONS: Therapeutic ultrasound,
with frequency of 1 MHz, intensity of 0.2 W/cm(2) (SATA) and pulsed mode, for 30
minutes, was able to increase the proliferation of preosteoblast-like bone cells.
This effect was mediated by a calcium influx, with a consequent activation of the
mTOR pathway, through increased NF-kappaB1 and p38alpha.
PMID- 26414999
TI - Serological evidence for the presence of influenza D virus in small ruminants.
AB - Influenza D virus (FLUDV) was isolated from diseased pigs with respiratory
disease symptoms in 2011, and since then the new virus has also been spread to
cattle. Little is known about the susceptibility of other agricultural animals
and poultry to FLUDV. This study was designed to determine if other farm animals
such as goats, sheep, chickens, and turkey are possible hosts to this newly
emerging influenza virus. 648 goat and sheep serum samples and 250 chicken and
turkey serum samples were collected from 141 small ruminant and 25 poultry farms
from different geographical locations in the United States and Canada. Serum
samples were examined using the hemagglutination inhibition (HI) assay and the
sheep and goat samples were further analyzed using the serum neutralization
assay. Results of this study showed FLUDV antibodies were detected in 13.5%
(17/126) of the sampled sheep farms, and 5.2% (29/557) of tested sheep serum
samples were positive for FLUDV antibodies. For the goat results, the FLUDV
antibodies were detected in 13.3% (2/15) of the sampled farms, and 8.8% (8/91) of
the tested goat serum samples were positive for FLUDV antibodies. Furthermore,
all tested poultry serum samples were negative for FLUDV antibodies. Our data
demonstrated that sheep and goat are susceptible to FLUDV virus and multiple
states in U.S. have this virus infection already in these two species. This new
finding highlights a need for future surveillance of FLUDV virus in small
ruminants toward better understanding both the origin and natural reservoir of
this new virus.
PMID- 26415000
TI - Determination of 11 quinolones in bovine milk using immunoaffinity stir bar
sorptive microextraction and liquid chromatography with fluorescence detection.
AB - A sensitive, selective and reproducible immunoaffinity stir bar sorptive
microextraction (SBSME) coupled with liquid chromatography-fluorescence method
for determination of 11 quinolones (QNs) in bovine milk was developed and
validated. It is first report of a broad-specificity monoclonal antibody to QNs
that has been immobilized to glass bar for preparation of a re-usable
immunoaffinity stir bar. Analytes were extracted by placing stir bar in milk and
shaking on a rotary shaker for 30min at 30rpm, followed by liquid chromatography
and fluorescence detection. The newly developed method has limits of detection
for each QN from 0.05 to 0.1ng/g with intra-day and inter-day precision ranging
from 3.2 to 11.9% and from 5.2 to 12.5%, respectively. This allowed us to
quantitatively analyze drugs in bovine milk with the advantage of significantly
simplified sample preparation. The proposed method was successfully applied to
the bovine milk samples analyses with QNs, demonstrating its rare application in
animal food safety analysis.
PMID- 26415001
TI - Muscular Dystrophy Mutations Impair the Nuclear Envelope Emerin Self-assembly
Properties.
AB - More than 100 genetic mutations causing X-linked Emery-Dreifuss muscular
dystrophy have been identified in the gene encoding the integral inner nuclear
membrane protein emerin. Most mutations are nonsense or frameshift mutations that
lead to the absence of emerin in cells. Only very few cases are due to missense
or short in-frame deletions. Molecular mechanisms explaining the corresponding
emerin variants' loss of function are particularly difficult to identify because
of the mostly intrinsically disordered state of the emerin nucleoplasmic region.
We now demonstrate that this EmN region can be produced as a disordered monomer,
as revealed by nuclear magnetic resonance, but rapidly self-assembles in vitro.
Increases in concentration and temperature favor the formation of long
curvilinear filaments with diameters of approximately 10 nm, as observed by
electron microscopy. Assembly of these filaments can be followed by fluorescence
through Thioflavin-T binding and by Fourier-transform Infrared spectrometry
through formation of beta-structures. Analysis of the assembly properties of five
EmN variants reveals that del95-99 and Q133H impact filament assembly capacities.
In cells, these variants are located at the nuclear envelope, but the
corresponding quantities of emerin-emerin and emerin-lamin proximities are
decreased compared to wild-type protein. Furthermore, variant P183H favors EmN
aggregation in vitro, and variant P183T provokes emerin accumulation in
cytoplasmic foci in cells. Substitution of residue Pro183 might systematically
favor oligomerization, leading to emerin aggregation and mislocalization in
cells. Our results suggest that emerin self-assembly is necessary for its proper
function and that a loss of either the protein itself or its ability to self
assemble causes muscular dystrophy.
PMID- 26415002
TI - 3D Printed Microtransporters: Compound Micromachines for Spatiotemporally
Controlled Delivery of Therapeutic Agents.
AB - Functional compound micromachines are fabricated by a design methodology using 3D
direct laser writing and selective physical vapor deposition of magnetic
materials. Microtransporters with a wirelessly controlled Archimedes screw
pumping mechanism are engineered. Spatiotemporally controlled collection,
transport, and delivery of micro particles, as well as magnetic nanohelices
inside microfluidic channels are demonstrated.
PMID- 26415003
TI - When Should a Positive Surgical Margin Ring a Bell? An Analysis of a Multi
Institutional Robot-Assisted Laparoscopic Radical Prostatectomy Database.
AB - OBJECTIVE: The impact of positive surgical margin (SM) on cancer control outcomes
in prostate cancer patients is a subject of continuous debate. We test the
hypothesis that the impact of SM on clinical recurrence (CR) rate may vary based
on the other clinical/pathologic characteristics of the tumor. MATERIALS AND
METHODS: We focused on 5290 patients treated with robot-assisted radical
prostatectomy and pelvic node dissection, between 2002 and 2013, at three
tertiary care centers. Regression tree analysis stratified patients into risk
groups based on their tumor characteristics and the corresponding CR rate. Kaplan
Meier log-rank and multivariable Cox regression models tested the relationship
between SM status and CR rate in each tree-generated risk group. RESULTS: Mean
(median) follow-up time was 47.7 (39.0) months. Regression tree analysis that
considered all available covariates, except SM status, divided patients based on
their CR risk into the following risk groups: (1) high risk (any pT3b/pT4
disease); (2) intermediate risk (<=pT3a disease and pGS 8-10); (3) low risk
(<=pT3a, pGS <=7, and prostate-specific antigen [PSA] >9 ng/mL); and (4) very low
risk (<=pT3a, pGS <=7, and PSA <=9 ng/mL). Positive SM had a significant
detrimental impact on CR risk only in two groups: intermediate risk (p < 0.001)
and high risk (p = 0.01). These observations were confirmed by multivariable
analyses. CONCLUSIONS: Our findings show that positive SM had a detrimental
impact on CR only in a minority of patients (15%), specifically in those with
advanced pathologic stage and/or pathologically poorly differentiated tumor. For
all the remaining patients (85%), positive SM by itself did not increase the risk
of CR.
PMID- 26415004
TI - Aryl Hydrocarbon Receptor Deficiency Attenuates Oxidative Stress-Related
Mesangial Cell Activation and Macrophage Infiltration and Extracellular Matrix
Accumulation in Diabetic Nephropathy.
AB - AIMS: Activation of glomerular mesangial cells (MCs) and functional changes of
renal tubular cells are due to metabolic abnormalities, oxidative stress, and
matrix accumulation in the diabetic nephropathy (DN). Aryl hydrocarbon receptor
(AhR) activation has been implicated in DN. In this study, we investigated the
role of AhR in the pathophysiological processes of DN using AhR knockout (AhRKO)
and pharmacological inhibitor alpha-naphthoflavone mouse models. RESULTS: The
increased blood glucose, glucose intolerance, MC activation, macrophage
infiltration, and extracellular matrix (ECM) accumulation were significantly
attenuated in AhRKO mice with diabetic inducer streptozotocin (STZ) treatment.
AhR deficiency by genetic knockout or pharmacological inhibition also decreased
the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), lipid
peroxidation, oxidative stress, NADPH oxidase activity, and N-E
carboxymethyllysine (CML, a major advanced glycation end product) in STZ-induced
diabetic mice. CML showed remarkably increased AhR/COX-2 DNA-binding activity,
protein-DNA interactions, gene regulation, and ECM formation in MCs and renal
proximal tubular cells, which could be reversed by siRNA-AhR transfection. CML
increased AhR nuclear translocation and biological activity in MCs and renal
proximal tubular cells could also be effectively attenuated by antioxidants.
INNOVATION: We elucidate for the first time that AhR plays an important role in
MC activation, macrophage infiltration, and ECM accumulation in DN conferred by
oxidative stress. CONCLUSIONS: AhR-regulated COX-2/PGE2 expression and ECM
deposition through oxidative stress cascade is involved in the CML-triggered MC
activation and macrophage infiltration. These findings suggest new insights into
the development of therapeutic approaches to reduce diabetic microvascular
complications. Antioxid. Redox Signal. 24, 217-231.
PMID- 26415005
TI - Low concentrations of metal mixture exposures have adverse effects on selected
biomarkers of Xenopus laevis tadpoles.
AB - Polluted ecosystems may contain mixtures of metals, such that the combinations of
metals, even in low concentrations, may cause adverse effects. In the present
study, we focused on toxic effects of mixtures of selected metals, the LC50
values, and also their safety limit in aquatic systems imposed by the European
legislation using a model organism. Xenopus laevis tadpoles were used as test
organisms. They were exposed to metals or their combinations due to 96-h LC50
values. Glutathione S-transferase (GST), glutathione reductase (GR),
acetylcholinesterase (AChE), carboxylesterase (CaE), glutathione peroxidase
(GPx), and catalase (CAT) levels were evaluated. Metallothionein concentrations
were also determined. The LC50s for Cd, Pb, and Cu were calculated as 5.81mg
AI/L, 123.05mg AI/L, and 0.85mg AI/L, respectively. Low lethality ratios were
observed with unary exposure of each metal in lower concentrations. Double or
triple combinations of LC50 and LC50/2 concentrations caused 100% lethality with
Cd+Cu and Pb+Cd+Cu mixtures, while the Pb+Cu mixture also caused high lethal
ratios. The selected enzyme activities were significantly affected by metals or
mixtures, and dose-related effects were determined. The metallothionein levels
generally increased as related to concentration in unary metals and mixtures.
Acceptable limit values of unary metals and mixtures did not significantly change
metallothionein levels. The results suggest that oxidative stress-related
mechanisms are involved in the toxicity induced by selected metals with
combinations of very low concentrations.
PMID- 26415007
TI - MyCompoundID MS/MS Search: Metabolite Identification Using a Library of Predicted
Fragment-Ion-Spectra of 383,830 Possible Human Metabolites.
AB - We report an analytical tool to facilitate metabolite identification based on an
MS/MS spectral match of an unknown to a library of predicted MS/MS spectra of
possible human metabolites. To construct the spectral library, the known
endogenous human metabolites in the Human Metabolome Database (HMDB) (8,021
metabolites) and their predicted metabolic products via one metabolic reaction in
the Evidence-based Metabolome Library (EML) (375,809 predicted metabolites) were
subjected to in silico fragmentation to produce the predicted MS/MS spectra. This
spectral library is hosted at the public MCID Web site ( www.MyCompoundID.org ),
and a spectral search program, MCID MS/MS, has been developed to allow a user to
search one or a batch of experimental MS/MS spectra against the library spectra
for possible match(s). Using MS/MS spectra generated from standard metabolites
and a human urine sample, we demonstrate that this tool is very useful for
putative metabolite identification. It allows a user to narrow down many possible
structures initially found by using an accurate mass search of an unknown
metabolite to only one or a few candidates, thereby saving time and effort in
selecting or synthesizing metabolite standard(s) for eventual positive metabolite
identification.
PMID- 26415009
TI - Harmful algal blooms should be treated as contaminants.
PMID- 26415006
TI - Prevalence and clinical significance of nodular regenerative hyperplasia in liver
biopsies.
AB - BACKGROUND: Nodular regenerative hyperplasia (NRH) is a rare histological
disorder associated with a wide variety of systemic diseases. AIMS: We aimed (i)
to report the prevalence of NRH in a database of liver biopsies (LBs) and the
frequency of portal hypertension (PHT) at diagnosis, and (ii) to investigate
whether associated diseases and/or specific histological lesions, including
abnormalities of the microvasculature, were related to PHT. METHODS: Patients
with a histological diagnosis of NRH, referred by seven clinical departments,
were retrospectively selected. Clinical, biological, radiological, haemodynamic
and endoscopic data at diagnosis were recorded. LBs were reassessed for
microvascular abnormalities. RESULTS: NRH was diagnosed in 4.4% of LBs (n = 159,
male: 52%, mean age: 54). Among patients referred for unexplained liver enzyme
abnormalities, 15% had NRH. PHT was present at diagnosis in 45 patients (38%),
including 13 with portal thrombosis; 65% of patients had an associated disorder.
Obliteration of portal vein branches, observed in the LBs of 17 patients (11%),
was significantly associated with PHT (P = 0.02). Periportal angiomatosis,
observed in 101 patients (63%), was associated with the absence of PHT (P < 10(
4) ). CONCLUSION: We suggest that NRH is a frequent histological lesion in the
setting of unexplained liver enzyme abnormalities. PHT is present at the time of
diagnosis in 1/3 of patients regardless of the presence of associated disease.
The frequency of periportal angiomatosis in NRH without obliteration of portal
vein branches, and its association with the absence of PHT suggest that
obstructive portal venopathy would not represent the most frequent mechanism
involved in NRH.
PMID- 26415010
TI - A multi-attribute decision analysis for decommissioning offshore oil and gas
platforms.
AB - The 27 oil and gas platforms off the coast of southern California are reaching
the end of their economic lives. Because their decommissioning involves large
costs and potential environmental impacts, this became an issue of public
controversy. As part of a larger policy analysis conducted for the State of
California, we implemented a decision analysis as a software tool (PLATFORM) to
clarify and evaluate decision strategies against a comprehensive set of
objectives. Key options selected for in-depth analysis are complete platform
removal and partial removal to 85 feet below the water line, with the remaining
structure converted in place to an artificial reef to preserve the rich
ecosystems supported by the platform's support structure. PLATFORM was
instrumental in structuring and performing key analyses of the impacts of each
option (e.g., on costs, fishery production, air emissions) and dramatically
improved the team's productivity. Sensitivity analysis found that disagreement
about preferences, especially about the relative importance of strict compliance
with lease agreements, has much greater effects on the preferred option than does
uncertainty about specific outcomes, such as decommissioning costs. It found a
near-consensus of stakeholders in support of partial removal and "rigs-to-reefs"
program. The project's results played a role in the decision to pass legislation
enabling an expanded California "rigs-to-reefs" program that includes a mechanism
for sharing cost savings between operators and the state.
PMID- 26415019
TI - Clinical and molecular diagnosis of pathologic complete response in rectal
cancer.
AB - The current standard approach to locally advanced rectal cancer involves pre
operative chemoradiotherapy followed by total mesorectal excision. This practice
is supported by several studies that have demonstrated superior local control
with this approach. This strategy, leads to a pathologic complete response (pCR)
in a substantial proportion of patients treated with neoadjuvant therapy.
Furthermore, pCR has been shown to be a reliable predictor of improved oncologic
outcomes. This observation has led to an increased interest in the pursuit of
identifying clinical, radiographic, pathologic and biochemical predictors of pCR.
This review discusses the promising approaches to and most recent advancements in
predicting pCR in rectal cancer.
PMID- 26415018
TI - Noninvasive electrocardiographic imaging of chronic myocardial infarct scar.
AB - BACKGROUND: Myocardial infarction (MI) scar constitutes a substrate for
ventricular tachycardia (VT), and an accurate delineation of infarct scar may
help to identify reentrant circuits and thus facilitate catheter ablation. One of
the recent advancements in characterization of a VT substrate is its volumetric
delineation within the ventricular wall by noninvasive electrocardiographic
imaging. This paper compares, in four specific cases, epicardial and volumetric
inverse solutions, using magnetic resonance imaging (MRI) with late gadolinium
enhancement as a gold standard. METHODS: For patients with chronic MI, who
presented at Glasgow Western Infirmary, delayed-enhancement MRI and 120-lead body
surface potential mapping (BSPM) data were acquired and 4 selected cases were
later made available to a wider community as part of the 2007 PhysioNet/Computers
in Cardiology Challenge. These data were used to perform patient-specific inverse
solutions for epicardial electrograms and morphology-based criteria were applied
to delineate infarct scar on the epicardial surface. Later, the Rochester group
analyzed the same data by means of a novel inverse solution for reconstructing
intramural transmembrane potentials, to delineate infarct scar in three
dimensions. Comparison of the performance of three specific inverse-solution
algorithms is presented here, using scores based on the 17-segment ventricular
division scheme recommended by the American Heart Association. RESULTS: The
noninvasive methods delineating infarct scar as three-dimensional (3D) intramural
distribution of transmembrane action potentials outperform estimates providing
scar delineation on the epicardial surface in all scores used for comparison. In
particular, the extent of infarct scar (its percentage mass relative to the total
ventricular mass) is rendered more accurately by the 3D estimate. Moreover, the
volumetric rendition of scar border provides better clues to potential targets
for catheter ablation. CONCLUSIONS: Electrocardiographic inverse solution
providing transmural distribution of ventricular action potentials is a promising
tool for noninvasively delineating the extent and location of chronic MI scar.
Further validation on a larger data set with detailed gold-standard data is
needed to confirm observations reported in this study.
PMID- 26415022
TI - Modified Genomic Sequencing PCR Using the MiSeq Platform to Identify Retroviral
Integration Sites.
AB - High-throughput mapping of retroviral vector integration sites (RIS) has become
an invaluable tool to evaluate novel gene therapy vectors and to track clonal
contribution in preclinical and clinical studies. Beard et al. (Methods Mol Biol
2014;1185:321-344) described an improved protocol developed for efficient
capture, sequencing, and analysis of RIS that preserves gene-modified clonal
contribution information. Here we describe adaptations to the previously
published modified genomic sequencing PCR (MGS-PCR) protocol using the Illumina
MiSeq paired-end sequencing platform. Lentiviral, gammaretroviral, and foamy
virus vector integrations were analyzed. MGS-PCR using the MiSeq platform allows
for the use of merged paired-end reads, which allows for efficient localization
of RIS to published genomes.
PMID- 26415024
TI - Red-Shifting Azobenzene Photoswitches for in Vivo Use.
AB - Recently, there has been a great deal of interest in using the photoisomerization
of azobenzene compounds to control specific biological targets in vivo. These azo
compounds can be used as research tools or, in principle, could act as optically
controlled drugs. Such "photopharmaceuticals" offer the prospect of targeted drug
action and an unprecedented degree of temporal control. A key feature of azo
compounds designed to photoswitch in vivo is the wavelength of light required to
cause the photoisomerization. To pass through tissue such as the human hand,
wavelengths in the red, far-red, or ideally near infrared region are required.
This Account describes our attempts to produce such azo compounds. Introducing
electron-donating or push/pull substituents at the para positions delocalizes the
azobenzene chromophore and leads to long wavelength absorption but usually also
lowers the thermal barrier to interconversion of the isomers. Fast thermal
relaxation means it is difficult to produce a large steady state fraction of the
cis isomer. Thus, specifically activating or inhibiting a biological process with
the cis isomer would require an impractically bright light source. We have found
that introducing substituents at all four ortho positions leads to azo compounds
with a number of unusual properties that are useful for in vivo photoswitching.
When the para substituents are amide groups, these tetra-ortho substituted azo
compounds show unusually slow thermal relaxation rates and enhanced separation of
n-pi* transitions of cis and trans isomers compared to analogues without ortho
substituents. When para positions are substituted with amino groups, ortho
methoxy groups greatly stabilize the azonium form of the compounds, in which the
azo group is protonated. Azonium ions absorb strongly in the red region of the
spectrum and can reach into the near-IR. These azonium ions can exhibit robust
cis-trans isomerization in aqueous solutions at neutral pH. By varying the nature
of ortho substituents, together with the number and nature of meta and para
substituents, long wavelength switching, stability to photobleaching, stability
to hydrolysis, and stability to reduction by thiols can all be crafted into a
photoswitch. Some of these newly developed photoswitches can be used in whole
blood and show promise for effective use in vivo. It is hoped they can be
combined with appropriate bioactive targets to realize the potential of
photopharmacology.
PMID- 26415023
TI - Microneedle fractional radiofrequency increases epidermal hyaluronan and reverses
age-related epidermal dysfunction.
AB - BACKGROUND AND OBJECTIVE: Skin aging results in physiological alterations in
keratinocyte activities and epidermal function, as well as dermal changes. Yet,
the cellular and molecular mechanisms that cause epidermal dysfunction during
skin aging are not well understood. Recently, the role of epidermal hyaluronan
(HA) as an active regulator of dynamic cellular processes is getting attention
and alterations in HA metabolism are thought to be important in age-related
epidermal dysfunction. Microneedle fractional radiofrequency (RF) has shown
effects for improving cutaneous aging. However, little is known about the effects
of fractional RF on the epidermal HA and epidermal function. We investigated the
effect of microneedle fractional RF on the expression of epidermal HA in young
and aged mice epidermis. MATERIALS AND METHODS: We performed fractional RF on the
dorsal skin of 30 8-week-old (young) hairless mice and 15 47-week-old (aged)
C57BL/6J mice. Skin samples were collected on day 1, 3, and 7. HA content was
measured by ELISA. Gene expressions of CD 44, HABP4, and HAS3 were measured using
real time RT-PCR. Immunohistochemistry for detection of HA, CD44, PCNA, and
filaggrin were performed. RESULTS: HA content and the mRNA levels of HABP4, CD44,
and HAS3 were upregulated in the epidermis of both young and aged mice after
microneedle fractional RF treatment. The expression was increased from day 1
after treatment and increased expression persisted on day 7. Fractional RF
treatment significantly increased PCNA and filaggrin expression only in the aged
mice skin. CONCLUSION: Microneedle fractional RF increased epidermal HA and CD44
expression in both young and aged mice and reversed age-related epidermal
dysfunction especially in aged mice, suggesting a new mechanism involved in the
skin rejuvenation effect of microneedle fractional RF.
PMID- 26415025
TI - Discovery of a novel neuroprotectant, BHDPC, that protects against MPP+/MPTP
induced neuronal death in multiple experimental models.
AB - Progressive degeneration and death of neurons are main causes of
neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease.
Although some current medicines may temporarily improve their symptoms, no
treatments can slow or halt the progression of neuronal death. In this study, a
pyrimidine derivative, benzyl 7-(4-hydroxy-3-methoxyphenyl)-5-methyl-4,7
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (BHDPC), was found to attenuate
dramatically the MPTP-induced death of dopaminergic neurons and improve behavior
movement deficiency in zebrafish, supporting its potential neuroprotective
activity in vivo. Further study in rat organotypic cerebellar cultures indicated
that BHDPC was able to suppress MPP(+)-induced cell death of brain tissue slices
ex vivo. The protective effect of BHDPC against MPP(+) toxicity was also
effective in human neuroblastoma SH-SY5Y cells through restoring abnormal changes
in mitochondrial membrane potential and numerous apoptotic regulators. Western
blotting analysis indicated that BHDPC was able to activate PKA/CREB survival
signaling and further up-regulate Bcl2 expression. However, BHDPC failed to
suppress MPP(+)-induced cytotoxicity and the increase of caspase 3 activity in
the presence of the PKA inhibitor H89. Taken together, these results suggest that
BHDPC is a potential neuroprotectant with prosurvival effects in multiple models
of neurodegenerative disease in vitro, ex vivo, and in vivo.
PMID- 26415026
TI - Metallothionein plays a prominent role in the prevention of diabetic nephropathy
by sulforaphane via up-regulation of Nrf2.
AB - Sulforaphane (SFN) prevents diabetic nephropathy (DN) in type 1 diabetes via up
regulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, it has
not been addressed whether SFN also prevents DN from type 2 diabetes or which
Nrf2 downstream gene(s) play(s) the key role in SFN renal protection. Here we
investigated whether Nrf2 is required for SFN protection against type 2 diabetes
induced DN and whether metallothionein (MT) is an Nrf2 downstream antioxidant
using Nrf2 knockout (Nrf2-null) mice. In addition, MT knockout mice were used to
further verify if MT is indispensable for SFN protection against DN. Diabetes
increased albuminuria, renal fibrosis, and inflammation were significantly
prevented by SFN, and Nrf2 and MT expression was increased. However, SFN renal
protection was completely lost in Nrf2-null diabetic mice, confirming the pivotal
role of Nrf2 in SFN protection from type 2 diabetes-induced DN. Moreover, SFN
failed to up-regulate MT in the absence of Nrf2, suggesting that MT is an Nrf2
downstream antioxidant. MT deletion resulted in a partial, but significant
attenuation of SFN renal protection from type 2 diabetes, demonstrating a partial
requirement for MT for SFN renal protection. Therefore, the present study
demonstrates for the first time that as an Nrf2 downstream antioxidant, MT plays
an important, though partial, role in mediating SFN renal protection from type 2
diabetes.
PMID- 26415027
TI - The cytoprotective effect of nitrite is based on the formation of dinitrosyl iron
complexes.
AB - Nitrite protects various organs from ischemia-reperfusion injury by ameliorating
mitochondrial dysfunction. Here we provide evidence that this protection is due
to the inhibition of iron-mediated oxidative reactions caused by the release of
iron ions upon hypoxia. We show in a model of isolated rat liver mitochondria
that upon hypoxia, mitochondria reduce nitrite to nitric oxide (NO) in amounts
sufficient to inactivate redox-active iron ions by formation of inactive
dinitrosyl iron complexes (DNIC). The scavenging of iron ions in turn prevents
the oxidative modification of the outer mitochondrial membrane and the release of
cytochrome c during reoxygenation. This action of nitrite protects mitochondrial
function. The formation of DNIC with nitrite-derived NO could also be confirmed
in an ischemia-reperfusion model in liver tissue. Our data suggest that the
formation of DNIC is a key mechanism of nitrite-mediated cytoprotection.
PMID- 26415029
TI - Immediate breastfeeding and skin-to-skin contact during cesarean section
decreases maternal oxidative stress, a prospective randomized case-controlled
study.
AB - OBJECTIVE: Immediate skin-to-skin contact (ISSC) and early breastfeeding are
recommended for the wellbeing of the neonate. In this study, we aimed to evaluate
the effect of ISSC and early breastfeeding on maternal oxidative stress and
postoperative pain. METHODS: A total of 90 patients were randomized into two
groups based on the timing of skin-to-skin contact and breastfeeding. Group 1 (n
= 45) was provided ISSC and breastfeeding in the operating room during the
cesarean section (C/S). Group 2 (n = 45) breastfed their babies 1 h after the
C/S. As markers of oxidative stress, maternal serum levels of total antioxidant
status (TAS), total oxidant status (TOS) and oxidative stress indices (OSI) were
evaluated. Maternal oxytocin levels and the relation between these parameters and
postoperative pain were also evaluated. RESULTS: The postoperative TAS levels
were significantly higher, whereas TOS and OSI levels were lower in Group 1 than
Group 2. Negative correlations between oxytocin level and postoperative TOS and
OSI were observed, as was a positive correlation between oxytocin level and
postoperative TAS. CONCLUSIONS: The effect of ISSC and early breastfeeding on
mothers was documented for the first time in this study. Our results demonstrated
ISSC and early breastfeeding during C/S reduce maternal oxidative stress.
PMID- 26415028
TI - Nutrition and the science of disease prevention: a systems approach to support
metabolic health.
AB - Progress in nutritional science, genetics, computer science, and behavioral
economics can be leveraged to address the challenge of noncommunicable disease.
This report highlights the connection between nutrition and the complex science
of preventing disease and discusses the promotion of optimal metabolic health,
building on input from several complementary disciplines. The discussion focuses
on (1) the basic science of optimal metabolic health, including data from gene
diet interactions, microbiome, and epidemiological research in nutrition, with
the goal of defining better targets and interventions, and (2) how nutrition,
from pharma to lifestyle, can build on systems science to address complex issues.
PMID- 26415030
TI - Mechanical Properties of Nanoscopic Lipid Domains.
AB - The lipid raft hypothesis presents insights into how the cell membrane organizes
proteins and lipids to accomplish its many vital functions. Yet basic questions
remain about the physical mechanisms that lead to the formation, stability, and
size of lipid rafts. As a result, much interest has been generated in the study
of systems that contain similar lateral heterogeneities, or domains. In the
current work we present an experimental approach that is capable of isolating the
bending moduli of lipid domains. This is accomplished using neutron scattering
and its unique sensitivity to the isotopes of hydrogen. Combining contrast
matching approaches with inelastic neutron scattering, we isolate the bending
modulus of ~13 nm diameter domains residing in 60 nm unilamellar vesicles, whose
lipid composition mimics the mammalian plasma membrane outer leaflet.
Importantly, the bending modulus of the nanoscopic domains differs from the
modulus of the continuous phase surrounding them. From additional structural
measurements and all-atom simulations, we also determine that nanoscopic domains
are in-register across the bilayer leaflets. Taken together, these results inform
a number of theoretical models of domain/raft formation and highlight the fact
that mismatches in bending modulus must be accounted for when explaining the
emergence of lateral heterogeneities in lipid systems and biological membranes.
PMID- 26415032
TI - Serum vaspin and adiponectin levels in patients with prolactinoma.
AB - BACKGROUND: Studies investigating serum vaspin and adiponectin levels in patients
with prolactinoma are inconclusive. The aim of this study was to evaluate serum
vaspin and adiponectin levels in patients with prolactinoma and healthy controls.
METHODS: A total of 42 prolactinoma patients (Group 1, 21 patients; Group 2, 21
patients) and 30 healthy controls were enrolled in the study. Group 1 consisted
of newly diagnosed patients who were never treated or had not received a dopamine
agonist (DA) within 6 months prior to screening. Group 2 consisted of
prolactinoma patients who were on DA treatment for at least 6 months at the time
of screening. The control group (group 3) consisted of healthy controls. RESULTS:
Patients with prolactinoma had higher homeostasis model assessment of insulin
resistance and lower quantitative insulin sensitivity check index values in
comparison to healthy controls (p < 0.001 for both). Serum levels of adiponectin
and vaspin were also significantly lower in prolactinoma patients when compared
to the control group (p < 0.01 and p < 0.001, respectively). Following adjustment
for confounding factors, the respective odds ratios for prolactinoma in patients
in the lower subgroup compared with those in the higher subgroup for adiponectin
and vaspin were 2.733 (0.621-12.035; p > 0.05) and 5.041 (1.191-21.339; p <
0.05). CONCLUSION: This is the first study to demonstrate the presence of low
vaspin levels in patients with prolactinomas. Further studies are needed to help
establish the roles of vaspin and adiponectin in prolactinoma patients.
PMID- 26415031
TI - F429 Regulation of Tunnels in Cytochrome P450 2B4: A Top Down Study of Multiple
Molecular Dynamics Simulations.
AB - The root causes of the outcomes of the single-site mutation in enzymes remain by
and large not well understood. This is the case of the F429H mutant of the
cytochrome P450 (CYP) 2B4 enzyme where the substitution, on the proximal surface
of the active site, of a conserved phenylalanine 429 residue with histidine seems
to hamper the formation of the active species, Compound I (porphyrin cation
radical-Fe(IV) = O, Cpd I) from the ferric hydroperoxo (Fe(III)OOH-, Cpd 0)
precursor. Here we report a study based on extensive molecular dynamic (MD)
simulations of 4 CYP-2B4 point mutations compared to the WT enzyme, having the
goal of better clarifying the importance of the proximal Phe429 residue on CYP
2B4 catalytic properties. To consolidate the huge amount of data coming from five
simulations and extract the most distinct structural features of the five species
studied we made an extensive use of cluster analysis. The results show that all
studied single polymorphisms of F429, with different side chain properties: i)
drastically alter the reservoir of conformations accessible by the protein,
perturbing global dynamics ii) expose the thiolate group of residue Cys436 to the
solvent, altering the electronic properties of Cpd0 and iii) affect the various
ingress and egress channels connecting the distal sites with the bulk
environment, altering the reversibility of these channels. In particular, it was
observed that the wild type enzyme exhibits unique structural features as
compared to all mutant species in terms of weak interactions (hydrogen bonds)
that generate a completely different dynamical behavior of the complete system.
Albeit not conclusive, the current computational investigation sheds some light
on the subtle and critical effects that proximal single-site mutations can exert
on the functional mechanisms of human microsomal CYPs which should go rather far
beyond local structure characterization.
PMID- 26415033
TI - Sensory and sympathetic disorders in chronic non-specific neck pain.
AB - The signs of sympathetic and sensory nerve-related disorders are not widely
investigated in chronic nonspecific neck pain (NNP) patients. Thus, we performed
skin temperature (Tsk), evaporation and touch threshold (TT) measurements to
reveal possible dysfunctions at the fingertips of NNP patients (n=60) compared
with healthy controls (n=11). Neck pain intensity was the main modifier of Tsk,
and age the main modifier of TT in a multivariate model. On comparisons of the
subgroups of NNP patients with unilateral (n=26) and bilateral (n=34) symptoms
and controls, TT differed and Tsk tended to differ, the unilateral pain patients
being found to demonstrate higher TT values on both sides. Interrelations between
the measured parameters were found in the controls, but not in the patients. The
NNP patients exhibited signs of functional impairment of innervation reflected in
changes in tactile sensitivity and vasoactive sympathetic function. These changes
may be based on both central and peripheral mechanisms, which possibly differ in
patients with unilateral and bilateral symptoms.
PMID- 26415035
TI - A randomized, double-blind, placebo-controlled clinical trial of the efficacy of
treatment with zinc in children with intractable epilepsy.
AB - This study was conducted to assess the efficacy of oral zinc supplementation in
children with intractable epilepsy. Forty-five children aged between three and 12
years and diagnosed with idiopathic intractable epilepsy at Assiut University
Hospital, Assiut, Egypt were recruited. The patients were randomly allocated to
two groups: the intervention group received oral zinc supplementation (1
mg/kg/day) while the placebo group received placebo, each for six months. The
parents of each child filled in a detailed questionnaire that covered demographic
characteristics, type of seizures, frequency, duration of seizures, previous
hospital admissions, postictal phenomena and the occurrence of status
epilepticus. The primary outcome (frequency of seizures) was compared between the
two groups. Zinc supplementation resulted in a significant reduction of seizure
frequency in 31% of the treated children. Zinc is an important trace element. Our
results suggest that it has mildly beneficial effects in children with
intractable epilepsy. We recommend further investigation of oral zinc
supplementation as an adjunctive therapy for managing intractable epilepsy in
children. Zinc therapy may be an option in treatment protocols for intractable
epilepsy in the near future.
PMID- 26415036
TI - A novel functional glucose transporter in the white shrimp Litopenaeus vannamei
LvGLUT2- is up-regulated during hypoxia in hepatopancreas.
AB - In hypoxia conditions, the white shrimp Litopenaeus vannamei shifts its energetic
metabolism from aerobic to anaerobic, requiring more glucose uptake into the
cells by GLUT proteins. We here report a novel glucose transporter in shrimp. The
Lvglut2 cDNA is 2473 bp-long containing an ORF of 1458 bp encoding 486 amino acid
residues. The deduced protein has the features of a facilitative sugar
transporter. The Lvglut2 gene product tagged with GFP was expressed in the cell
membrane of Xenopus oocytes. In the same expression system, untagged LvGLUT2
resulted to be a bidirectional glucose transporter that functions moving glucose
down its concentration gradient in and out of the cell. Lvglut2 mRNA is expressed
in hepatopancreas while in muscle and gills it was not detected. Hypoxia up
regulates the expression of Lvglut2 transcripts in hepatopancreas. These results
provide a better understanding of facilitative glucose transporters and gene
regulation during hypoxia in crustaceans.
PMID- 26415037
TI - Constructing Human Skin Equivalents on Porcine Acellular Peritoneum Extracellular
Matrix for In Vitro Irritation Testing.
AB - The irritancy of topical products has to be investigated to ensure the safety and
compliance. Although several reconstructed human epidermal models have been
adopted by the Organization for Economic Cooperation and Development (OECD) to
replace in vivo animal irritation testing, these models are based on a single
cell type and lack dermal components, which may be insufficient to reflect all of
the components of irritation. In our study, we investigated the use of acellular
porcine peritoneum extracellular matrix as a substrate to construct full
thickness human skin equivalents (HSEs) for use as irritation screening tool. The
acellular peritoneum matrix (APM) exhibited excellent skin cell attachment (>80%)
and proliferation for human dermal fibroblasts (HDF) and immortalized human
keratinocytes (HaCaT). APM-HSEs based on coculture of HDF and HaCaT were
prepared. Increased HDF seeding density up to 5 * 10(4)/cm(2) resulted in APM
HSEs with a thicker and more organized epidermis. The epidermis of APM-HSEs
expressed keratin 15, a keratinocyte proliferation marker, and involucrin, a
differentiation marker, respectively. To assess the use of APM-HSEs for
irritation testing, six proficiency chemicals, including three nonirritants
(phosphate-buffered saline, polyethylene glycol 400, and isopropanol) and three
irritants (1-bromohexane, heptanol, and sodium dodecyl sulfate) were applied. The
APM-HSEs were able to discriminate nonirritants from irritants based on the
viability. Levels of cytokines (interleukin [IL]-1alpha, IL-1ra, IL-6, IL-8, and
granulocyte macrophage colony-stimulating factor [GM-CSF]) in these treatment
groups further assisted the irritancy ranking. In conclusion, we have developed
partially differentiated full-thickness APM-HSEs based on acellular porcine
peritoneum matrix, and these APM-HSEs demonstrated utility as an in vitro
irritation screening tool.
PMID- 26415038
TI - Characteristics and Survival of Anti-U1 RNP Antibody-Positive Patients With
Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.
AB - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a severe complication of
connective tissue diseases (CTDs). This study aimed to investigate the clinical
and hemodynamic characteristics and survival of anti-U1 RNP-positive patients
with CTD-associated PAH, with a focus on systemic sclerosis (SSc)-associated PAH.
METHODS: We implemented a prospective database that included patients with CTD
associated PAH for whom there were clinical, autoantibody, and mortality data. We
compared clinical and hemodynamic characteristics to anti-U1 RNP antibody status.
We then assessed whether anti-U1 RNP antibodies could be a prognostic factor in
CTD-associated PAH with a focus on SSc-associated PAH. RESULTS: We studied a
total of 342 patients with CTD-associated PAH, of whom 36 (11%) were anti-U1 RNP
antibody positive. Anti-U1 RNP-positive patients were younger and less
functionally impaired than were anti-U1 RNP-negative patients in CTD- and SSc
associated PAH. Hemodynamic parameters were similar in anti-U1 RNP-positive and
anti-U1 RNP-negative patients. In CTD-associated PAH, anti-U1 RNP positivity was
associated with decreased mortality in univariable analysis (hazard ratio 0.34
[95% confidence interval 0.18-0.65], P < 0.001). In multivariable analysis, anti
U1 RNP positivity was also associated with decreased mortality (hazard ratio 0.44
[95% confidence interval 0.20-0.97], P = 0.043) independently of age, sex,
functional parameters, lung involvement, and hemodynamic parameters. Results were
similar in SSc-associated PAH, although the association between anti-U1 RNP
positivity and survival did not reach significance in univariable (hazard ratio
0.47 [95% confidence interval 0.22-1.02], P = 0.055) and multivariable (hazard
ratio 0.47 [95% confidence interval 0.20-1.11], P = 0.085) analyses. CONCLUSION:
Anti-U1 RNP positivity was associated with distinct clinical characteristics and
survival in CTD- and SSc-associated PAH. While hemodynamic parameters were
similar in anti-U1 RNP-positive and anti-U1 RNP-negative patients, our results
suggest that anti-U1 RNP positivity could be a factor protecting against
mortality in CTD- and SSc-associated PAH.
PMID- 26415039
TI - Novel fluorine-containing DAPY derivatives as potent HIV-1 NNRTIs: a patent
evaluation of WO2014072419.
AB - Diarylpyrimidine (DAPY) derivatives, one family of HIV non-nucleoside reverse
transcriptase (RT) inhibitors (NNRTIs) with superior activities against wild-type
(WT) HIV-1 and NNRTI-resistant strains, have attracted much attention in the past
decade. A series of DAPY derivatives featuring a fluorine atom on the central
ring were reported as novel NNRTIs in the patent WO2014072419. Some compounds
exhibited robust potency against both WT and mutant strains, which were
approximately equal to or higher than those of the reference drug TMC120.
Moreover, it has become evident that fluorinated molecules have a remarkable
record in many other potent NNRTIs. Thus, this survey provides a sampling of
renowned fluorinated NNRTIs and their mode of action, with an analysis clarifying
the functional roles and impact of fluorine substitution on antiviral potency. We
envision that fluorinated NNRTIs will play a continuing role in affording anti
HIV drug candidates for therapeutic applications.
PMID- 26415040
TI - Near surface properties of mixtures of propylammonium nitrate with n-alkanols 2.
Nanotribology and fluid dynamics.
AB - Colloid probe friction force microscopy (FFM) has been used to study the
lubricity of propylammonium nitrate (PAN) mixed with n-alkanols confined between
sliding silica and mica surfaces. Mixtures of PAN with butanol, hexanol, octanol
and dodecanol were investigated for various n-alkanol volume fractions to
elucidate the effect of n-alkanol hydrocarbon chain length and concentration on
shear forces. For all n-alkanols friction decreases with n-alkanol vol%. The
trends in friction reduction with n-alkanol vol% do not correlate with changes in
the bulk phase viscosity or the near surface nanostructure, and colloid probe
atomic force microscope (AFM) fluid dynamic measurements showed that none of the
mixtures shear thin. Thus, the reduction in friction is attributed to the n
alkanol disrupting solvophobic interactions between boundary layer propylammonium
ions adsorbed to the mica and near surface liquid layers. The lowest friction is
obtained for pure dodecanol, which is attributed to the dodecanol forming a
robust boundary layer. Friction for the other pure n-alkanols is higher because
the lateral attractions between adsorbed n-alkanols are too weak to facilitate
the formation of a strong boundary layer, commensurate with the decreased
hydrocarbon chain length.
PMID- 26415041
TI - Intrathecal Acetyl-L-Carnitine Protects Tissue and Improves Function after a Mild
Contusive Spinal Cord Injury in Rats.
AB - Primary and secondary ischemia after spinal cord injury (SCI) contributes to
tissue and axon degeneration, which may result from decreased energy substrate
availability for cellular and axonal mitochondrial adenosine triphosphate (ATP)
production. Therefore, providing spinal tissue with an alternative energy
substrate during ischemia may be neuroprotective after SCI. To assess this, rats
received a mild contusive SCI (120 kdyn, Infinite Horizons impactor) at thoracic
level 9 (T9), which causes loss of ~ 80% of the ascending sensory dorsal column
axonal projections to the gracile nucleus. Immediately afterwards, the energy
substrate acetyl-L-carnitine (ALC; 1 mg/day) or phosphate-buffered saline (PBS)
was infused intrathecally (sub-arachnoid) for 6 days via an L5/6 catheter
attached to a subcutaneous Alzet pump. ALC treatment improved overground
locomotor function (Basso-Beattie-Breshnahan [BBB] score 18 vs. 13) at 6 days,
total spared epicenter (71% vs. 57%) and penumbra white matter (90% vs. 85%),
ventral penumbra microvessels (108% vs. 79%), and penumbra motor neurons (42% vs.
15%) at 15 days post-SCI, compared with PBS treatment. However, the ascending
sensory projections (anterogradely traced with cholera toxin B from the sciatic
nerves) and dorsal column white matter and perfused blood vessels were not
protected. Furthermore, grid walking, a task we have shown to be dependent on
dorsal column function, was not improved. Thus, mitochondrial substrate
replacement may only be efficacious in areas of lesser or temporary ischemia,
such as the ventral spinal cord and injury penumbra in this study. The current
data also support our previous evidence that microvessel loss is central to
secondary tissue degeneration.
PMID- 26415042
TI - A Woman With a Novel Mutation of THAP1 With a Prominent Response to Deep Brain
Stimulation of the Globus Pallidus Internus.
PMID- 26415044
TI - Histopathologic Findings of Patients With Biopsy-Negative Giant Cell Arteritis
Compared to Those Without Arteritis: A Population-Based Study.
AB - OBJECTIVE: To evaluate whether there are histopathologic features of negative
temporal artery biopsy (TAB) that allow differentiation between patients with
giant cell arteritis (GCA) and those without. METHODS: All consecutive patients
with negative TAB seen between January 2009 and December 2012 were selected
retrospectively. Demographic, clinical, and laboratory data at presentation and
at each followup visit were collected. A pathologist with expertise in vasculitis
and blinded to clinical data and final diagnosis reviewed all negative TABs.
Histopathologic features evaluated were the presence of a focal mediointimal
scar, medial attenuation, intimal hyperplasia, fragmentation of inner elastic
lamina, calcification, adventitial fibrosis, and neoangiogenesis. RESULTS: After
a median (interquartile range [IQR]) followup period of, respectively, 19 months
(9.2-31.2) and 26.3 months (4.9-36.7) (P = 0.041), 38 (55%) of 69 patients had a
final diagnosis of TAB-negative GCA, while in the remaining 31 (45%) of 69
patients GCA was excluded. The American College of Rheumatology classification
criteria for GCA were satisfied by 31 (81.6%) of 38 patients and 2 (6.5%) of 31
patients (P < 0.0001). Compared to non-GCA patients, those with TAB-negative GCA
had more frequent cranial manifestations and higher erythrocyte sedimentation
rates and C-reactive protein levels. The frequency of patients receiving
prednisone, the mean dose, and the duration of prednisone treatment at TAB were
similar in the 2 groups. There were no significant differences between TAB
negative GCA and non-GCA patients in the frequencies of all the histologic
features evaluated. CONCLUSION: The histologic features of negative TABs
evaluated in this study do not allow for the differentiation between GCA and non
GCA patients. In the absence of an inflammatory infiltrate, other histologic
changes of the temporal artery wall are not specific for GCA.
PMID- 26415043
TI - Partial Correlation-Based Retinotopically Organized Resting-State Functional
Connectivity Within and Between Areas of the Visual Cortex Reflects More Than
Cortical Distance.
AB - Numerous studies have demonstrated functional magnetic resonance imaging (fMRI)
based resting-state functional connectivity (RSFC) between cortical areas. Recent
evidence suggests that synchronous fluctuations in blood oxygenation level
dependent fMRI reflect functional organization at a scale finer than that of
visual areas. In this study, we investigated whether RSFCs within and between
lower visual areas are retinotopically organized and whether retinotopically
organized RSFC merely reflects cortical distance. Subjects underwent retinotopic
mapping and separately resting-state fMRI. Visual areas V1, V2, and V3, were
subdivided into regions of interest (ROIs) according to quadrants and visual
field eccentricity. Functional connectivity (FC) was computed based on Pearson's
linear correlation (correlation), and Pearson's linear partial correlation
(correlation between two time courses after the time courses from all other
regions in the network are regressed out). Within a quadrant, within visual
areas, all correlation and nearly all partial correlation FC measures showed
statistical significance. Consistently in V1, V2, and to a lesser extent in V3,
correlation decreased with increasing eccentricity separation. Consistent with
previously reported monkey anatomical connectivity, correlation/partial
correlation values between regions from adjacent areas (V1-V2 and V2-V3) were
higher than those between nonadjacent areas (V1-V3). Within a quadrant, partial
correlation showed consistent significance between regions from two different
areas with the same or adjacent eccentricities. Pairs of ROIs with similar
eccentricity showed higher correlation/partial correlation than pairs distant in
eccentricity. Between dorsal and ventral quadrants, partial correlation between
common and adjacent eccentricity regions within a visual area showed statistical
significance; this extended to more distant eccentricity regions in V1. Within
and between quadrants, correlation decreased approximately linearly with
increasing distances separating the tested ROIs. Partial correlation showed a
more complex dependence on cortical distance: it decreased exponentially with
increasing distance within a quadrant, but was best fit by a quadratic function
between quadrants. We conclude that RSFCs within and between lower visual areas
are retinotopically organized. Correlation-based FC is nonselectively high across
lower visual areas, even between regions that do not share direct anatomical
connections. The mechanisms likely involve network effects caused by the dense
anatomical connectivity within this network and projections from higher visual
areas. FC based on partial correlation, which minimizes network effects, follows
expectations based on direct anatomical connections in the monkey visual cortex
better than correlation. Last, partial correlation-based retinotopically
organized RSFC reflects more than cortical distance effects.
PMID- 26415045
TI - The Silk flow-diverter stent for endovascular treatment of intracranial
aneurysms.
AB - Flow diverter (FD) stents represent a new endovascular technique developed for
the treatment of complex intracranial aneurysms (wide neck, fusiform, large, and
giant aneurysms) that are challenging for classic endovascular techniques such as
coiling, balloon-assisted coiling and stent-assisted coiling. Low porosity, high
metal coverage, and high pore density are the main properties of FD stents. These
properties induce hemodynamic changes redirecting the blood flow away from the
aneurysm and into the parent artery leading to gradual thrombosis of the
aneurysm. FD stents also provide scaffolding for subsequent neoendothelial
proliferation, and vessel wall remodeling. This is considered as a paradigm shift
compared to prior endovascular methods, which predominantly aimed at providing
treatment inside the aneurysmal sac. This paper describes in detail the first
released FD stent, the Silk flow-diverter stent (Balt Extrusion, Montmorency,
France), its mechanism of action and deployment technique. It reviews the
pertinent literature regarding safety, efficacy and potential risks and
complications associated with the use of this stent.
PMID- 26415046
TI - Content, Consistency, and Quality of Black Box Warnings: Time for a Change.
PMID- 26415047
TI - Traffic-related air pollution and risk for leukaemia of an adult population.
AB - Air pollution causes lung cancer, but associations with other cancers have not
been established. We investigated whether long-term exposure to traffic-related
air pollution is associated with the risk of the general population for
leukaemia. We identified 1,967 people in whom leukaemia was diagnosed in 1992
2010 from a nation-wide cancer registry and selected 3,381 control people at
random, matched on sex and year of birth, from the entire Danish population.
Residential addresses since 1971 were traced in a population registry, and
outdoor concentrations of NOx and NO2 , as indicators of traffic-related air
pollution, were calculated at each address in a dispersion model. We used
conditional logistic regression to estimate the risk for leukaemia after
adjustment for income, educational level, cohabitation status and co-morbidity.
In linear analyses, we found odds ratios for acute myeloid leukaemia of 1.20 (95%
confidence interval: 1.04-1.38) per 20 ug/m(3) increase in NOx and 1.31 (1.02
1.68) per 10 ug/m(3) increase in NO2 , calculated as time-weighted average
exposure at all addresses since 1971. We found no association with chronic
myeloid or lymphocytic leukaemia. This study indicates an association between
long-term exposure to traffic-related air pollution and acute myeloid leukaemia
in the general population, but not for other subtypes of leukaemia.
PMID- 26415048
TI - Secondary task and risky driving behavior: a test of the mediating effect of
situation awareness.
AB - A theoretical model is developed by using a contingency perspective to
hypothesize the relationship between a secondary task and risky driving behavior.
It is conjectured that the relationship between the two variables is mediated by
situation awareness (SA). An experiment is designed and administered to provide
empirical evidence. Thirty Indonesian students as subjects were required to carry
out a driving assignment in a simulated environment. Empirical evidence suggests
that SA provides a partial mediation effect towards the relationship between a
secondary task and risky driving behavior. It is also found that a secondary task
has a significant effect on risky driving behavior. The secondary task also
becomes a significant explanation of SA. In addition, working memory capacity,
experience and gender are found to have no significant impact towards SA.
PMID- 26415050
TI - Increasing motorcycle conspicuity - design and assessment of intervention to
enhance rider safety.
PMID- 26415049
TI - Outcomes of Systematic Review of Ureteroscopy for Stone Disease in the Obese and
Morbidly Obese Population.
AB - PURPOSE: With a rising incidence of obesity and urolithiasis, we wanted to look
at the outcomes of ureteroscopy (URS) for stone management in this group of
patients. METHODS: We did a systematic review of literature in accordance with
Cochrane review and preferred reporting items for systematic reviews and meta
analyses (PRISMA) guidelines on all English language articles between 1990 and
June 2015 for URS and stone treatment in obese patients. Data were retrieved for
patient and stone demographics, outcomes of URS, complications, and follow-up.
RESULTS: Fifteen studies (835 patients) were identified with a mean age of 49
years and a mean body mass index (BMI) of 40.5 kg/m(2). The overall stone size
was 14.2 mm (range: 3-72 mm) with almost a third of the stones in the lower pole.
The initial and final stone-free rate (SFR) was 76.9% and 82.5%, respectively,
with an overall complication rate of 9.3% (n = 78). Except one patient with
myocardial infarction, all other complications were Clavien grade I-III. The
complication rate for morbidly obese patients (17.6%) was twice that of the obese
patients (8.4%), although they were all graded as Clavien I or II. CONCLUSION:
URS and stone fragmentation are safe and efficient treatment methods in obese
patients with a good SFR and a relatively low complication rate, although the
complications tend to be higher in the morbidly obese patients.
PMID- 26415052
TI - In vitro and in vivo correlates of physiological and neoplastic human Fallopian
tube stem cells.
AB - High-grade serous cancer (HGSC) progresses to advanced stages without symptoms
and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and
Fallopian tubes in patients with BRCA1 or BRCA2 mutations have documented a pre
metastatic intramucosal neoplasm that is found almost exclusively in the
Fallopian tube, termed 'serous tubal intraepithelial carcinoma' or STIC.
Moreover, other proliferations, termed p53 signatures, secretory cell outgrowths
(SCOUTs), and lower-grade serous tubal intraepithelial neoplasms (STINs) fall
short of STIC but share similar alterations in expression, in keeping with an
underpinning of genomic disturbances involved in, or occurring in parallel with,
serous carcinogenesis. To gain insight into the cellular origins of this unique
tubal pathway to high-grade serous cancer, we cloned and both immortalized and
transformed Fallopian tube stem cells (FTSCs). We demonstrated that pedigrees of
FTSCs were capable of multipotent differentiation and that the tumours derived
from transformed FTSCs shared the histological and molecular features of HGSC. We
also demonstrated that altered expression of some biomarkers seen in transformed
FTSCs and HGSCs (stathmin, EZH2, CXCR4, CXCL12, and FOXM1) could be seen as well
in immortalized cells and their in vivo counterparts SCOUTs and STINs. Thus, a
whole-genome transcriptome analysis comparing FTSCs, immortalized FTSCs, and
transformed FTSCs showed a clear molecular progression sequence that is
recapitulated by the spectrum of accumulated perturbations characterizing the
range of proliferations seen in vivo. Biomarkers unique to STIC relative to
normal tubal epithelium provide a basis for novel detection approaches to early
HGSC, but must be viewed critically given their potential expression in lesser
proliferations. Perturbations shared by both immortalized and transformed FTSCs
may provide unique early targets for prevention strategies. Central to these
efforts has been the ability to clone and perpetuate multipotent FTSCs.
PMID- 26415053
TI - A multidimensional model of mothers' perceptions of parent alcohol socialization
and adolescent alcohol misuse.
AB - We assessed a multidimensional model of parent alcohol socialization in which key
socialization factors were considered simultaneously to identify combinations of
factors that increase or decrease risk for development of adolescent alcohol
misuse. Of interest was the interplay between putative risk and protective
factors, such as whether the typically detrimental effects on youth drinking of
parenting practices tolerant of some adolescent alcohol use are mitigated by an
effective overall approach to parenting and parental modeling of modest alcohol
use. The sample included 1,530 adolescents and their mothers; adolescents' mean
age was 13.0 (SD = .99) at the initial assessment. Latent profile analysis was
conducted of mothers' reports of their attitude toward teen drinking, alcohol
specific parenting practices, parental alcohol use and problem use, and overall
approach to parenting. The profiles were used to predict trajectories of
adolescent alcohol misuse from early to middle adolescence. Four profiles were
identified: 2 profiles reflected conservative alcohol-specific parenting
practices and 2 reflected alcohol-tolerant practices, all in the context of other
attributes. Alcohol misuse accelerated more rapidly from Grade 6 through 10 in
the 2 alcohol-tolerant compared with conservative profiles. Results suggest that
maternal tolerance of some youth alcohol use, even in the presence of dimensions
of an effective parenting style and low parental alcohol use and problem use, is
not an effective strategy for reducing risky adolescent alcohol use. (PsycINFO
Database Record
PMID- 26415054
TI - The effects of e-cigarette visual appearance on craving and withdrawal symptoms
in abstinent smokers.
AB - Electronic cigarette (e-cigarette) use is becoming increasing popular among
smokers, and there is a plethora of devices available. Nicotine delivery is
clearly important for reducing tobacco craving and withdrawal symptoms, but other
sensorimotor aspects of e-cigarettes (such as visual appearance) may contribute
to this effect. This study explored whether it is important for an e-cigarette to
visually resemble a tobacco cigarette in order to reduce craving and withdrawal
symptoms. Sixty-three cigarette smokers (40% female, aged 18-65 years) who were
not current e-cigarette users were randomly allocated to take ten 3-s puffs from
either a white or a red first-generation e-cigarette following overnight
abstinence. Current craving (urge to smoke) and nicotine withdrawal symptoms
(using the Mood and Physical Symptoms Scale [MPSS]) were measured before and 10
min after use. Linear regression revealed higher craving and withdrawal symptoms
in the red condition versus the white condition, but only among those who were e
cigarette naive (craving: B = .76, p = .009; withdrawal symptoms: B = 2.18, p =
.009), not among those with e-cigarette experience (craving: B = -.08, p = .89;
withdrawal symptoms: B = .24, p = .81), and these effects differed between groups
(p = .04 and 0.01 for craving and withdrawal symptoms, respectively). In
conclusion, cigarette-like appearance was associated with lower craving and
withdrawal symptoms, but only for those with no prior e-cigarette experience.
This effect, putatively mediated via classical conditioning or expectancies, may
aid understanding of smokers' initial preferences for "cigalike" e-cigarette
devices.
PMID- 26415051
TI - Pharmacology and Clinical Drug Candidates in Redox Medicine.
AB - SIGNIFICANCE: Oxidative stress is suggested to be a disease mechanism common to a
wide range of disorders affecting human health. However, so far, the
pharmacotherapeutic exploitation of this, for example, based on chemical
scavenging of pro-oxidant molecules, has been unsuccessful. RECENT ADVANCES: An
alternative emerging approach is to target the enzymatic sources of disease
relevant oxidative stress. Several such enzymes and isoforms have been identified
and linked to different pathologies. For some targets, the respective
pharmacology is quite advanced, that is, up to late-stage clinical development or
even on the market; for others, drugs are already in clinical use, although not
for indications based on oxidative stress, and repurposing seems to be a viable
option. CRITICAL ISSUES: For all other targets, reliable preclinical validation
and drug ability are key factors for any translation into the clinic. In this
study, specific pharmacological agents with optimal pharmacokinetic profiles are
still lacking. Moreover, these enzymes also serve largely unknown physiological
functions and their inhibition may lead to unwanted side effects. FUTURE
DIRECTIONS: The current promising data based on new targets, drugs, and drug
repurposing are mainly a result of academic efforts. With the availability of
optimized compounds and coordinated efforts from academia and industry
scientists, unambiguous validation and translation into proof-of-principle
studies seem achievable in the very near future, possibly leading towards a new
era of redox medicine.
PMID- 26415055
TI - Temporal variation in facilitator and client behavior during group motivational
interviewing sessions.
AB - There is considerable evidence for motivational interviewing (MI) in changing
problematic behaviors. Research on the causal chain for MI suggests influence of
facilitator speech on client speech. This association has been examined using
macro (session-level) and micro (utterance-level) measures; however, effects
across sessions have largely been unexplored, particularly with groups. We
evaluated a sample of 129 adolescent Group MI sessions, using a behavioral coding
system and timing information to generate information on facilitator and client
speech (CT; change talk) within 5 successive segments (quintiles) of each group
session. We hypothesized that facilitator speech (open-ended questions and
reflections of CT) would be related to subsequent CT. Repeated measures analysis
indicated significant quadratic and cubic trends for facilitator and client
speech across quintiles. Across quintiles, cross-lagged panel analysis using a
zero-inflated negative binomial model showed minimal evidence of facilitator
speech on client CT, but did indicate several effects of client CT on facilitator
speech, and of client CT on subsequent client CT. Results suggest that session
level effects of facilitator speech on client speech do not arise from long
duration effects of facilitator speech; instead, we detected effects of
facilitator speech on client speech only at the beginning and end of sessions,
when open questions, respectively, suppressed and enhanced client expressions of
CT. Findings suggest that clinicians must remain vigilant to client CT throughout
the group session, reinforcing it when it arises spontaneously and selectively
employing open-ended questions to elicit it when it does not, particularly toward
the end of the session.
PMID- 26415056
TI - Young adult veteran perceptions of peers' drinking behavior and attitudes.
AB - Social norms-based interventions have shown promise in reducing drinking behavior
and the resulting consequences in young adults. Although most research has
focused on young civilians (i.e., college students), some studies have
investigated social norms-based interventions with active-duty military and
veteran samples. Yet, research has not yet determined how to maximize the
effectiveness of social norms-based interventions in this heavy-drinking
population. As an initial step toward this goal, the current study utilized a
community sample of 1,023 young adult veterans to examine (a) whether veteran
perceptions of the drinking behavior of their veteran peers differ from their
perceptions of civilian drinking behavior, (b) whether perceptions of specific
veteran groups differ from the actual drinking behavior of veterans within those
groups, (c) what levels of specificity in reference groups (same-gender
civilians, same-branch veterans, same-gender veterans, or same-branch-and-gender
veterans) are most strongly associated with veterans' own drinking, and (d)
whether perceptions about others' attitudes toward drinking also contribute
independently of perceived behavioral norms to veteran drinking. Findings
indicated that participants perceived that other veterans drank more than
civilians and that veteran groups drank more than veterans in the sample actually
drank. Veteran-specific perceived behavioral norms were similar in their
associations with drinking outcomes, whereas same-gender civilian perceived
behavioral norms exhibited little or no associations with drinking. Veteran
specific perceived attitudinal norms exhibited little or no association with
drinking behavior after controlling for perceived behavioral norms. These
findings can be used to inform the development of social norms interventions for
young adult veterans.
PMID- 26415058
TI - Parental involvement in brief interventions for adolescent marijuana use.
AB - Adolescents (aged 12-18 years) identified in a school setting as abusing
marijuana and other drugs were randomly assigned to complete 1 of 2 brief
interventions (BIs). Adolescents and their parent (N = 259) were randomly
assigned to receive either a 2-session adolescent only (BI-A) or a 2-session
adolescent and additional parent session (BI-AP). Interventions were manualized
and delivered in a school setting by trained counselors. Adolescents were
assessed at intake and at 6 months following the completion of the intervention.
Using a latent construct representing 6-month marijuana use outcomes, current
findings supported previous research that BI-AP resulted in superior outcomes
when compared to BI-A. The presence of a marijuana dependence diagnosis at
baseline predicted poorer outcomes when compared to youth without a diagnosis.
Both baseline diagnostic status and co-occurring conduct problems interacted with
intervention condition in predicting marijuana use outcomes. A marijuana
dependence diagnosis resulted in poorer marijuana use outcomes within the BI-A
condition when compared to BI-AP. Co-occurring conduct problems were associated
with poorer marijuana use outcomes within the BI-AP intervention when compared to
BI-A. Implications for implementing BIs given diagnostic status, parent
involvement, and co-occurring conduct problems are discussed.
PMID- 26415057
TI - Associations between neighborhood alcohol availability and young adolescent
alcohol use.
AB - We investigated the association between alcohol outlet density and adolescent
alcohol use, including whether this association differed by sociodemographic
characteristics. We geocoded and mapped active license data from the year 2011 to
calculate the number of outlets within multiple circular buffers of varying sizes
(density), centered at households of adolescents ages 10-16 (n = 2,724). We
examined 2 indicators of alcohol use: any lifetime use, but not in past month,
and any past month heavy use. Cross-sectional hierarchal multivariate regression
analyses were used to examine associations between alcohol outlet density and
alcohol use, including the potential moderating effect of age, gender,
race/ethnicity, and socioeconomic status. Analyses controlled for neighborhood
level socioeconomic status and accounted for census tract-level clustering. A
higher number of on- and off-premise outlets within 0.10, 0.25, and 0.50 miles
around the respondents' homes was associated with higher odds of being a heavy
drinker. In addition, the number of on-premise outlets within the 0.25-mile
radius was associated with greater odds of lifetime drinking. For on-premise
outlets where minors were not allowed (clubs/bars), we observed a positive and
significant association between clubs/bars within the 0.25-mile buffer zone and
higher odds of both lifetime and heavy drinking. Findings suggest that youth who
are exposed to higher densities of on-premise alcohol outlets are at risk for
both lifetime use and recent heavy use. It is critical to advocate for stricter
laws limiting the number of alcohol outlets in neighborhoods, including
clubs/bars where minors are restricted, and putting into place more stringent
enforcement of age identification requirements to limit distribution of alcohol
to minors.
PMID- 26415059
TI - Can marijuana make it better? Prospective effects of marijuana and temperament on
risk for anxiety and depression.
AB - Increases in marijuana use in recent years highlight the importance of
understanding how marijuana affects mental health. Of particular relevance is the
effect of marijuana use on anxiety and depression given that marijuana use is
highest among late adolescents/early adults, the same age range in which risk for
anxiety and depression is the highest. Here we examine how marijuana use
moderates the effects of temperament on level of anxiety and depression in a
prospective design in which baseline marijuana use and temperament predict
anxiety and depression 1 year later. We found that harm avoidance (HA) is
associated with higher anxiety and depression a year later, but only among those
low in marijuana use. Those higher in marijuana use show no relation between HA
and symptoms of anxiety and depression. Marijuana use also moderated the effect
of novelty seeking (NS), with symptoms of anxiety and depression increasing with
NS only among those with high marijuana use. NS was unrelated to symptoms of
anxiety and depression among those low in marijuana use. The temperament
dimension of reward dependence was unrelated to anxiety and depression symptoms.
Our results suggest that marijuana use does not have an invariant relationship
with anxiety and depression, and that the effects of relatively stable
temperament dimensions can be moderated by other contextual factors.
PMID- 26415060
TI - Associations among trauma, posttraumatic stress disorder, cannabis use, and
cannabis use disorder in a nationally representative epidemiologic sample.
AB - Research in community and clinical samples has documented elevated rates of
cannabis use and cannabis use disorders (CUDs) among individuals with trauma
exposure and posttraumatic stress disorder (PTSD). However, there is a lack of
research investigating relations between, and correlates of, trauma and cannabis
phenotypes in epidemiologic samples. The current study examined associations
between trauma (i.e., lifetime trauma exposure and PTSD) and cannabis phenotypes
(i.e., lifetime cannabis use and CUD) in a nationally representative sample.
Participants were individuals who participated in Waves 1 and 2 of the National
Epidemiologic Survey on Alcohol and Related Conditions (n = 34,396; 52.4% women;
age, M = 48.0 years, SD = 16.9). Lifetime DSM-IV Criterion A trauma exposure was
significantly associated with lifetime cannabis use (OR = 1.215) but was only
marginally associated with CUD (OR = 0.997). Within the trauma-exposed sample,
lifetime PTSD showed a significant association with CUD (OR = 1.217) but was only
marginally associated with lifetime cannabis use (OR = 0.992). Partially
consistent with hypotheses, lifetime trauma was associated with greater odds of
lifetime cannabis use, whereas PTSD was associated with greater odds of CUD.
Longitudinal research investigating patterns of onset of these events/disorders
is needed.
PMID- 26415061
TI - Variability in medical marijuana laws in the United States.
AB - Marijuana use and its distribution raise several complex health, social, and
legal issues in the United States. Marijuana is prohibited in only 23 states and
promarijuana laws are likely to be introduced in these states in the future.
Increased access to and legalization of medical marijuana may have an impact on
recreational marijuana use and perception through increased availability and
decreased restrictiveness around the drug. The authors undertook an analysis to
characterize the policy features of medical marijuana legislation, including an
emphasis on the types of medical conditions that are included in medical
marijuana laws. A high degree of variability in terms of allowable medical
conditions, limits on cultivation and possession, and restrictiveness of policies
was discovered. Further research is needed to determine if this variability
impacts recreational use in those states.
PMID- 26415063
TI - Premeditation moderates the relation between sensation seeking and risky
substance use among young adults.
AB - Young adulthood is a peak period for externalizing behaviors such as substance
abuse and antisocial conduct. Evidence from developmental neuroscience suggests
that externalizing conduct within this time period may be associated with a
"developmental asymmetry" characterized by an early peak in sensation seeking
combined with a relatively immature impulse control system. Trait measures of
impulsivity-sensation seeking and premeditation-are psychological manifestations
of these respective systems, and multiple prior studies suggest that high
sensation seeking and low premeditation independently confer risk for distinct
forms of externalizing behaviors. The goal of the present study was to test this
developmental asymmetry hypothesis, examining whether trait premeditation
moderates the effect of sensation seeking on substance use and problems,
aggression, and rule-breaking behavior. Using a cross-sectional sample of college
enrolled adults (n = 491), we applied zero-inflated modeling strategies to
examine the likelihood and level of risky externalizing behaviors. Results
indicated that lower premeditation enhanced the effect of higher sensation
seeking on higher levels of positive and negative alcohol consequences, more
frequent drug use, and more problematic drug use, but was unrelated to individual
differences in antisocial behaviors. Our findings indicate that the developmental
asymmetry between sensation seeking and a lack of premeditation is a risk factor
for individual differences in problematic substance use among young adults, and
may be less applicable for antisocial behaviors among high functioning
individuals.
PMID- 26415062
TI - Do students use contextual protective behaviors to reduce alcohol-related sexual
risk? Examination of a dual-process decision-making model.
AB - Recent studies suggest drinking protective behaviors (DPBs) and contextual
protective behaviors (CPBs) can uniquely reduce alcohol-related sexual risk in
college students. Few studies have examined CPBs independently, and even fewer
have utilized theory to examine modifiable psychosocial predictors of students'
decisions to use CPBs. The current study used a prospective design to examine (a)
rational and reactive pathways and psychosocial constructs predictive of CPB use
and (b) how gender might moderate these influences in a sample of college
students. Students (n = 508) completed Web-based baseline (mid-Spring semester)
and 1- and 6-month follow-up assessments of CPB use; psychosocial constructs
(expectancies, normative beliefs, attitudes, and self-concept); and rational and
reactive pathways (intentions and willingness). Regression was used to examine
rational and reactive influences as proximal predictors of CPB use at the 6-month
follow-up. Subsequent path analyses examined the effects of psychosocial
constructs, as distal predictors of CPB use, mediated through the rational and
reactive pathways. Both rational (intentions to use CPB) and reactive
(willingness to use CPB) influences were significantly associated with increased
CPB use. The examined distal predictors were found to effect CPB use
differentially through the rational and reactive pathways. Gender did not
significantly moderate any relationships within in the model. Findings suggest
potential entry points for increasing CPB use that include both rational and
reactive pathways. Overall, this study demonstrates the mechanisms underlying how
to increase the use of CPBs in programs designed to reduce alcohol-related sexual
consequences and victimization.
PMID- 26415064
TI - The relationship between psychological distress and adolescent polydrug use.
AB - Polydrug use is relatively common among adolescents. Psychological distress is
associated with the use of specific drugs, and may be uniquely associated with
polydrug use. The purpose of this study was to test the association of
psychological distress with polydrug use using a large adolescent sample. The
sample consisted of 10,273 students aged 12-17 years from the State of Victoria,
Australia. Participants completed frequency measures of tobacco, alcohol,
cannabis, inhalant, and other drug use in the past 30 days, and psychological
distress. Control variables included age, gender, family socioeconomic status,
school suspensions, academic failure, cultural background, and peer drug use.
Drug-use classes were derived using latent-class analysis, then the association
of psychological distress and controls with drug-use classes was modeled using
multinomial ordinal regression. There were 3 distinct classes of drug use: no
drug use (47.7%), mainly alcohol use (44.1%), and polydrug use (8.2%).
Independent of all controls, psychological distress was higher in polydrug users
and alcohol users, relative to nondrug users, and polydrug users reported more
psychological distress than alcohol users. Psychological distress was most
characteristic of polydrug users, and targeted prevention outcomes may be
enhanced by a collateral focus on polydrug use and depression and/or anxiety.
PMID- 26415065
TI - Thresholds of probable problematic gambling involvement for the German
population: Results of the Pathological Gambling and Epidemiology (PAGE) Study.
AB - Consumption measures in gambling research may help to establish thresholds of low
risk gambling as 1 part of evidence-based responsible gambling strategies. The
aim of this study is to replicate existing Canadian thresholds of probable low
risk gambling (Currie et al., 2006) in a representative dataset of German
gambling behavior (Pathological Gambling and Epidemiology [PAGE]; N = 15,023).
Receiver-operating characteristic curves applied in a training dataset (60%)
extracted robust thresholds of low-risk gambling across 4 nonexclusive
definitions of gambling problems (1 + to 4 + Diagnostic and Statistical Manual
for Mental Disorders-Fifth Edition [DSM-5] Composite International Diagnostic
Interview [CIDI] symptoms), different indicators of gambling involvement (across
all game types; form-specific) and different timeframes (lifetime; last year).
Logistic regressions applied in a test dataset (40%) to cross-validate the
heuristics of probable low-risk gambling incorporated confounding covariates
(age, gender, education, migration, and unemployment) and confirmed the strong
concurrent validity of the thresholds. Moreover, it was possible to establish
robust form-specific thresholds of low-risk gambling (only for gaming machines
and poker). Possible implications for early detection of problem gamblers in
offline or online environments are discussed. Results substantiate international
knowledge about problem gambling prevention and contribute to a German discussion
about empirically based guidelines of low-risk gambling.
PMID- 26415066
TI - A 10-year estimate of the incidence of decompression illness in a discrete group
of recreational cave divers in Australia.
AB - INTRODUCTION: The vast majority of freshwater cave diving in Australia occurs
within the limestone caves of the Gambier karst in the south-east of South
Australia. The incidence of decompression illness (DCI) in cave divers is
presumed to be higher than open-water recreational divers because of the greater
depths involved, but has not previously been reported. Our aim was to determine
the incidence of DCI in cave divers, the patterns of diving and the outcome of
hyperbaric treatment. METHODS: This was a retrospective cohort study of cave
divers with DCI presenting to the Royal Adelaide Hospital or The Alfred Hospital
over a 10-year period between 2002 and 2012. We reviewed case notes of cave
divers who were treated for DCI after diving in the Mt Gambier karst. As there
are no records of the number of dives performed during the study period we
generated a denominator for the incidence of DCI by extrapolating available data
and making a number of assumptions about the number of dives per dive permit
issued. RESULTS: Sixteen patients were treated for DCI during the study period.
The precipitating dive was a single deep decompression dive in seven cases,
multiday repetitive dive sequences in eight and a non-decompression dive in one.
Three of the 16 cases of DCI involved dives in excess of 90 metres' fresh water
(mfw) using trimix. As the total estimated number of dives in the study period
was approximately 57,000 the incidence of DCI in Australian cave divers was
estimated to be 2.8:10,000 (0.028%). It is possible that the overall incidence of
DCI is as high as 0.05%, and even higher when dives to depths greater than 90 mfw
are involved. CONCLUSIONS: The estimated incidence of DCS in this series is lower
than expected but consistent with other series describing DCI in cold-water
recreational diving.
PMID- 26415067
TI - Provisional report on diving-related fatalities in Australian waters 2010.
AB - INTRODUCTION: An individual case review was conducted of known diving-related
deaths that occurred in Australia in 2010. METHOD: The case studies were compiled
using statements from witnesses and reports of the police and coroners. In each
case, the particular circumstances of the accident and details from the post
mortem examination, where available, are provided. A root cause analysis was made
for each case. RESULTS: There were 20 reported fatalities, one less than the
previous year. Five of the victims were female (four scuba divers) and 15 were
males. Twelve deaths occurred while snorkelling and/or breath-hold diving, seven
while scuba diving (one of whom was using a rebreather), and one diver died while
using surface supplied breathing apparatus. At least two breath-hold divers
likely drowned as a result of apnoeic hypoxia. Cardiac-related issues were
thought to have contributed to the deaths of at least three and possibly five
snorkellers, and of at least one, possibly two compressed gas divers.
CONCLUSIONS: Snorkelling or diving alone, poor supervision, apnoeic hypoxia, pre
existing medical conditions, lack of recent experience and unfamiliar and/or
poorly-functioning equipment were features in several deaths in this series.
Reducing delays to CT-scanning and autopsy and coroners' reports documenting that
the victim of a drowning was snorkelling or scuba diving at the time are aspects
of the investigation of these fatalities that could be improved.
PMID- 26415068
TI - Middle ear barotrauma in a tourist-oriented, condensed open-water diver
certification course: incidence and effect of language of instruction.
AB - INTRODUCTION: In Professional Association of Diving Instructors (PADI) Open Water
Diver certification courses that cater to tourists, instruction is often
condensed and potentially delivered in a language that is not the candidate's
native language. OBJECTIVE: To assess the incidence of middle ear barotrauma
(MEBt) in open-water diver candidates during a condensed four-day certification
course, and to determine if language of instruction affects the incidence of MEBt
in these divers. METHOD: The ears of participating diving candidates were
assessed prior to commencing any in-water compression. Tympanic membranes (TM)
were assessed and graded for MEBt after the confined and open-water training
sessions. Tympanometry was performed if the candidate had no movement of their TM
during Valsalva. Photographs were taken with a digital otoscope. RESULTS: Sixty
seven candidates participated in the study. Forty-eight had MEBt at some time
during their course. MEBt was not associated with instruction in non-native
language (adjusted odds ratio = 0.82; 95% confidence intervals 0.21-3.91). There
was also no significant association between the severity of MEBt and language of
instruction. CONCLUSION: Open-water diver candidates have a high incidence of
MEBt. Education in non-native language does not affect the overall incidence of
MEBt.
PMID- 26415069
TI - The prevalence of oro-facial barotrauma among scuba divers.
AB - INTRODUCTION: Barotrauma is a physical injury that results from ambient pressure
changes during flying, diving or hyperbaric oxygen therapy. The aim of this study
was to assess the prevalence of oro-facial barotrauma among a sample of scuba
divers in Jeddah, Saudi Arabia. MATERIALS AND METHODS: Data for the study were
collected through a self-reported questionnaire that was distributed to 166
divers. The questionnaire was divided into two parts, in which the first part
contained demographic data and the second part consists of multiple choice
questions and a few open-ended questions discussing the different signs and
symptoms of orofacial barotraumas. RESULTS: One-hundred-and-sixty-three divers
responded. The most frequent symptoms during diving were dry mouth (51.9%),
followed by clenching (32.5%) and temporomandibular joint (TMJ) pain (19.5%),
while the most frequent symptoms after diving were dry mouth (22.7%) followed by
clenching and facial pain (16.9%). CONCLUSIONS: Clenching and dry mouth were
common findings but are temporary in nature and do not warrant any dental
intervention. TMJ and facial pain were also reported but were temporary. The use
of commercial mouthpieces during diving may be related to more symptoms when
compared with customized types.
PMID- 26415070
TI - Does self-certification reflect the cardiac health of UK sport divers?
AB - BACKGROUND: Since 2009, the United Kingdom diving incident data show an
increasing number of fatalities in the over-50s age group. Previous studies also
suggest some divers take cardiac medications. Since 2001, diving medicals have
not been mandatory for UK sport divers. Instead, an annual medical self
certification form, submitted to their club/school or training establishment, is
required. We documented in a survey of UK sport divers the prevalence of cardiac
events and medications and the frequency of medical certifications. METHODS: An
anonymous on-line questionnaire was publicised. Measures included diver and
diving demographics, prescribed medications, diagnosed hypertension, cardiac
issues, events and procedures, other health issues, year of last diving medical,
diagnosed persistent foramen ovale (PFO), smoking and alcohol habits, exercise
and body mass index. RESULTS: Of 672 completed surveys, hypertension was reported
by 119 (18%) with 25 of these (21%) having not had a diving medical. Myocardial
infarction 6 (1%), coronary artery bypass grafting 3 (< 1%), atrial fibrillation
19 (3%) and angina 12 (2%) were also reported. PFOs were reported by 28 (4%),
with 20 of these opting for a closure procedure. From 83 treated incidences of
decompression illness (DCI), 19 divers reported that a PFO was diagnosed.
CONCLUSIONS: Divers inevitably develop health problems. Some continue to dive
with cardiac issues, failing to seek specialised diving advice or fully
understand the role of the diving medical. Physicians without appropriate
training in diving medicine may inform a diver they are safe to continue diving
with their condition without appreciating the potential risks. The current
procedure for medical screening for fitness to dive may not be adequate for all
divers.
PMID- 26415071
TI - Underwater blast injury: a review of standards.
AB - The first cases of underwater blast injury appeared in the scientific literature
in 1917, and thousands of service members and civilians were injured or killed by
underwater blast during WWII. The prevalence of underwater blast injuries and
occupational blasting needs led to the development of many safety standards to
prevent injury or death. Most of these standards were not supported by
experimental data or testing. In this review, we describe existing standards,
discuss their origins, and we comprehensively compare their prescriptions across
standards. Surprisingly, we found that most safety standards had little or no
scientific basis, and prescriptions across standards often varied by at least an
order of magnitude. Many published standards traced back to a US Navy 500 psi
guideline, which was intended to provide a peak pressure at which injuries were
likely to occur. This standard itself seems to have been based upon a completely
unfounded assertion that has propagated throughout the literature in subsequent
years. Based on the limitations of the standards discussed, we outline future
directions for underwater blast injury research, such as the compilation of
epidemiological data to examine actual injury risk by human beings subjected to
underwater blasts.
PMID- 26415072
TI - Cone shell envenomation: epidemiology, pharmacology and medical care.
AB - The marine environment presents much danger, specifically in regards to the
numerous venomous inhabitants within tropical and subtropical waters. The toxins
from one such group of venomous marine snails, commonly referred to as 'cone
snails', have been well documented in causing human fatalities. Yet information
regarding medical treatment for cone snail envenomation is limited and poorly
accessible. To correct this, medical and scientific expertise and literary review
on Conus provide a basic and comprehensive directive focused on the medical
treatment and post-mortem investigative analysis of cone snail envenomation. We
emphasize what we expect to be the most lethal feeding group of Conus and provide
a brief background to the epidemiology of their stings. We describe the venom
apparatus of Conus and its utility of rapid venom delivery. We have compiled the
documented incidences of Conus envenomation to offer thorough reference of known
signs and symptoms - this too drawing on personal experiences in the field. We
have also made available a brief background to the biochemistry and pharmacology
of Conus venoms to highlight their complex nature.
PMID- 26415073
TI - On diver thermal status and susceptibility to decompression sickness.
AB - In a recent Letter to the Editor, Clarke, et al, indicated that divers who
deliberately chill themselves on a dive to reduce risk of decompression sickness
(DCS) may be misinterpreting our 2007 Navy Experimental Diving Unit (NEDU)
report. Indeed, we did not advocate that divers should risk hypothermia on bottom
to reduce risk of DCS, nor do we dispute the authors' overall admonition to avoid
diving cold unnecessarily. However, Clarke, et al, imply more generally that
results of our study are not applicable to recreational or technical divers
because the dives we tested were atypical of dives undertaken by such divers. We
wish to clarify that our study does have implications for recreational and
technical divers, implications that should not be ignored. The dives we tested
were not intended to be typical of dives undertaken in any actual operational
context. Instead, we chose to expose divers to temperatures at the extremes of
their thermal tolerance in order to ensure that effects of diver thermal status
on DCS susceptibility would be found if such effects existed. Our initial test
dive profile provided appreciable time both on bottom and during decompression to
allow any differential thermal effects during these two dive phases to manifest,
while affording a baseline risk of DCS that could be altered by thermal effects
without exposing subjects to inordinately high risks of DCS. Our results strongly
indicate that the optimal diver thermal conditions for mitigation of DCS risk or
minimization of decompression time entail remaining cool during gas uptake phases
of a dive and warm during off-gassing phases. While the dose-response
characteristics of our observed thermal effects are almost certainly non-linear
in both exposure temperature and duration, it is only reasonable to presume that
the effects vary monotonically with these factors. We have no reason to presume
that such responses and effects under less extreme conditions would be in
directions opposite to those found under the conditions we tested. Similarly,
responses to thermal exposures even more extreme than we tested might not be
larger than the responses we observed, but it would be unwise to ignore the
trends in our results under some unfounded presumption that the effects reverse
with changes in thermal conditions beyond those tested. Finally, thermal effects
on bottom and during decompression in dives to depths other than the 120 feet of
sea water (fsw) or 150 fsw depths of the dives we tested are unlikely to be
qualitatively different from those observed in our tested dives. The original
question has therefore been answered: chill on bottom decreases DCS
susceptibility while chill during decompression increases DCS susceptibility.
Under conditions encountered by recreational or technical divers, the only open
issue is arguably magnitudes of effects, not directions. Neither does lack of
technology to control thermal status during a dive render our study results
inapplicable. It only renders the diver unable to actively optimize his or her
thermal exposure to minimize DCS risk or decompression obligation. Effects of
diver thermal status on bottom hold regardless of whether the dive has a
decompression long enough for a thermal effect to manifest in the decompression
phase of the dive. We pointed out that US Navy decompression tables have
historically been developed and validated with test dives in which divers were
cold and working during bottom phases and cold and resting during decompression
phases. Thus, our results indicate that it is not prudent for very warm divers to
challenge the US Navy no-stop limits. However, becoming deliberately chilled on
bottom only to remain cold during any ensuing decompression stops is similarly
ill-advised. We agree with Clarke et al. that relative conservatism of some dive
computer algorithms or alternative decompression tables, or the depth and time
roundups necessary to determine table-based prescriptions, work in the diver's
favour, but note that diving any profile to a shorter bottom time is a ready
means to reduce the risk of DCS - i.e., enhance safety - without compromising
comfort. Any active diver heating is best limited while on bottom to a minimal
level required to safely complete on-bottom tasks, and dialled up only during
decompression. Diver warming during decompression should not be so aggressive as
to risk heat stress, and care should be taken to ensure that divers remain
hydrated.
PMID- 26415074
TI - Re: Don't dive cold when you don't have to.
AB - The letter by Clarke et al unfortunately misrepresents the work at the US Navy
Experimental Diving Unit (NEDU) to which it refers, and delivers a confused
picture of the physiological impact of thermal status on decompression stress. A
series of earlier reports outline the importance of thermal status. Being warm
during a dive results in higher post-dive Doppler bubble scores. Hot water suits
are associated with a higher rate of decompression sickness (DCS) than passively
insulated drysuits. Post-dive cooling can prolong the risk window for developing
symptoms of skin bends.The NEDU chamber study provided an elegant design to
further assess the impact of thermal stress. Dives to 37 msw (120 fsw) were
divided into descent/bottom and ascent/stop phases, prolonging the latter so that
bottom times could be increased if results allowed without compromising the
experimental structure. The water temperature was held at either 36 degrees C
(97 degrees F; 'warm') or 27 degrees C (80 degrees F; 'cold'). The 'warm/cold'
exposure, with a bottom time of 30 minutes, yielded a DCS rate of 22% (7/32
subject-exposures). The 'cold/warm' bottom time was increased to 70 minutes and
still yielded a DCS rate of only 1.3% (2/158). Even if the effects are
exaggerated by the prolonged ascent/stop phase, the dramatic results demand
serious attention. Contrary to the claim made by Clarke et al in their letter,
the high temperature employed in the NEDU study could almost certainly be
maintained at the skin by a number of active heating garments available to the
diving public. Hot water suits are not required for the effect; and the 'cold'
study temperature (better described as 'cool') is clearly well within the range
experienced by divers. The statement by Clarke et al that "the Navy uses their
extensive mathematical expertise to select the one dive profile that, in their
estimation, is the most likely to identify a difference in decompression risk..."
is frankly baffling. Use of a single dive depth in no way invalidates the
relevance to other dive profiles. Similarly, it is not reasonable to characterize
skin temperatures lower than those produced in the study as "venturing into the
unknown" and thereby invalidating the results. Scientific method does encourage
the confirmation of findings. This goal, however, does not diminish the value of
singular, well-designed studies. The NEDU study is certainly one of these, most
valuable in reminding divers that factors beyond the pressure-time profile will
affect decompression risk. Divers must have adequate thermal protection to
function effectively (physically and cognitively) throughout a dive. However,
excessive warming during the descent/bottom phase increases inert gas uptake and
can compromise decompression safety. Practically, while it may be optimal for
divers to be cool or cold during the descent/bottom phase, it is prudent to
recommend a thermoneutral range and avoidance of any excessive warming. Being
cool during the ascent/stop phase inhibits inert gas elimination and can
compromise safety but sudden warming must be constrained to avoid reducing the
gas solubility of superficial tissues that could promote localized bubble
formation and symptoms of skin bends. Active heating systems are attractive, but
they have the potential to create the worst decompression stress condition;
excessive heating during the descent/bottom phase and cooling during the
ascent/stop phase if they fail part way through a dive. The risk is still
elevated, though, if the systems work throughout a dive. Gerth et al were able to
increase the bottom time to 70 minutes for both the 'coldwarm' and 'warm-warm'
conditions, but the rate of DCS was significantly lower for the 'cold-warm'
condition (see above). This lesson is relevant to any diving exposure.
Ultimately, divers need to be aware of the potential impact of thermal status.
Thermal protection should preserve clear thinking and physical performance, but
excessive manipulation should be avoided. For many, passive systems will provide
adequate and appropriate protection. For those who need or choose active warming
systems, thoughtful use is vital. Further research is required to quantify the
hazards and be able to incorporate thermal status into decompression algorithms
in a meaningful way.
PMID- 26415075
TI - Management of severe spinal cord injury following hyperbaric exposure.
AB - There is an increasing body of evidence that drainage of lumbar cerebrospinal
fluid (CSF) improves functional neurological outcome after reperfusion injury to
the spinal cord that occasionally follows aortic reconstructive surgery. This
beneficial effect is considered owing to lowering of the CSF pressure thereby
normalising spinal cord blood flow and reducing the 'secondary' cord injury
caused by vascular congestion and cord swelling in the relatively confined spinal
canal. Whilst lacking definitive proof, there are convincing randomised
controlled trials (RCTs), cohort data and systematic reviews supporting this
intervention. The therapeutic window for lumbar CSF drainage requires further
elucidation; however, it appears to be days rather than hours post insult. We
contend that the same benefit is likely to be achieved following other primary
spinal cord injuries that cause cord swelling and elicit the 'secondary' injury.
Traditionally the concept of CSF drainage has been considered more applicable to
the brain as contained in a 'closed box' by lowering intracranial pressure (ICP)
to improve cerebral perfusion pressure (CPP). The control of CPP is intended to
limit 'secondary' brain injury and is a key concept of brain injury management.
Using microdialysis in the spinal cords of trauma patients, it has been shown
that intraspinal pressure (ISP) needs to be kept below 20 mmHg and spinal cord
perfusion pressure (SCPP) above 70 mmHg to avoid biochemical evidence of
secondary cord damage. Vasopressor have also been used in spinal cord injury to
improve perfusion, however complications are common, typically cardiac in nature,
and require very careful monitoring; the evidence supporting this approach is
notably less convincing. Decompression illness (DCI) of the spinal cord is
treated with recompression, hyperbaric oxygen, various medications designed to
reduce the inflammatory response and fluid administration to normalise blood
pressure and haematocrit. These management protocols are based largely on
anecdote and transferred evidence from conventional cord trauma, as the low
numbers and sporadic nature of DCI in divers makes RCTs nigh on impossible.
Unfortunately even with best management, some patients are left with significant
neurological deficit. The 'iceberg phenomenon', occurs when patients with DCI of
the cord make a good neurological recovery but actually have profound cord damage
as revealed in one case some four years later at post mortem and another example
in a diver who developed late functional deterioration due to loss of neuronal
reserve. This clinical evidence, together with animal study data, support the
notion that even a modest preservation of spinal cord axons is associated with
significant improvement in neurological outcome. In the light of the positive
level two evidence in the vascular literature that CSF drainage limits
'secondary' injury thereby improving neurological outcome, we propose that
centres with appropriate clinical experience consider using lumbar CSF drainage
to normalise SCPP, as an adjunct to the conventional treatment of severe spinal
cord DCI. Divers with severe spinal cord DCI are generally in the most productive
years of their lives and, given the potentially devastating impact of this
condition, should be given the benefit of any possible adjuvant treatment that
may serve to improve long-term outcome.
PMID- 26415076
TI - Cytopathologic diagnosis of oncocytic type intraductal papillary mucinous
neoplasm: Criteria and clinical implications of accurate diagnosis.
AB - BACKGROUND: Cytologic findings of pancreatic oncocytic-type intraductal papillary
mucinous neoplasms (IPMNs)/intraductal oncocytic papillary neoplasms (IOPNs) are
largely unknown. METHODS: Five IOPNs encountered by the authors were analyzed.
RESULTS: Four IOPNs were located in the pancreatic head, and 1 was located in the
pancreatic body/tail in 2 men and 3 women ages 56 to 84 years (mean age, 66
years). Radiologic diagnoses included pancreatic ductal adenocarcinoma (PDAC) in
2 patients, invasive cancer associated with IPMN in 1 patient, IPMN versus
mucinous cystic neoplasm in 1 patient, and cystic mass in 1 patient. Cytologic
findings included: hypercellular smears (4 of 5 cases) containing well formed
clusters of oncocytic cells (5 of 5 cases) with prominent, slightly eccentric
nucleoli (4 of 5 cases), predominantly arranged in sheets/papillary units (5 of 5
cases), with punched-out intercytoplasmic spaces (4 of 5 cases), and with
occasional 3-dimensional groups and focal necrosis (3 of 5 cases). The
intracytoplasmic mucin and thick extracellular mucin typical of other IPMNs were
observed only in 2 cases and were very limited. The mean size on resection was
4.5 cm. Invasion was observed in 3 cases (0.1, 0.3, and 2.0 cm) of tubular-type
IPMN. Initial cytologic evaluation was performed by the authors in 4 of 5 cases,
which were diagnosed as IOPN (n = 3) and IPMN versus cystic PDAC (n = 1). One
case was initially misdiagnosed as PDAC and, on resection, proved to be
noninvasive IOPN. CONCLUSIONS: Cytologic features of IOPNs are classical, similar
to their histologic counterparts, and differ significantly from other IPMN
subtypes. Because of their highly complex appearance, they are often
radiologically misdiagnosed as PDAC; thus, failure to recognize their
characteristic features on fine-needle aspiration may lead to inappropriate
treatment. Patients with IOPN have an incomparably better prognosis than patients
with ordinary PDAC, even when their neoplasms are invasive.
PMID- 26415078
TI - Promoting Action on Research Implementation in Health Services framework applied
to TeamSTEPPS implementation in small rural hospitals.
AB - BACKGROUND: A particularly useful model for examining implementation of quality
improvement interventions in health care settings is the PARIHS (Promoting Action
on Research Implementation in Health Services) framework developed by Kitson and
colleagues. The PARIHS framework proposes three elements (evidence, context, and
facilitation) that are related to successful implementation. PURPOSES: An
evidence-based program focused on quality enhancement in health care, termed
TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety),
has been widely promoted by the Agency for Healthcare Research and Quality, but
research is needed to better understand its implementation. We apply the PARIHS
framework in studying TeamSTEPPS implementation to identify elements that are
most closely related to successful implementation. METHODOLOGY/APPROACH:
Quarterly interviews were conducted over a 9-month period in 13 small rural
hospitals that implemented TeamSTEPPS. Interview quotes that were related to each
of the PARIHS elements were identified using directed content analysis.
Transcripts were also scored quantitatively, and bivariate regression analysis
was employed to explore relationships between PARIHS elements and successful
implementation related to planning activities. FINDINGS: The current findings
provide support for the PARIHS framework and identified two of the three PARIHS
elements (context and facilitation) as important contributors to successful
implementation. PRACTICE IMPLICATIONS: This study applies the PARIHS framework to
TeamSTEPPS, a widely used quality initiative focused on improving health care
quality and patient safety. By focusing on small rural hospitals that undertook
this quality improvement activity of their own accord, our findings represent
effectiveness research in an understudied segment of the health care delivery
system. By identifying context and facilitation as the most important
contributors to successful implementation, these analyses provide a focus for
efficient and effective sustainment of TeamSTEPPS efforts.
PMID- 26415079
TI - Organizational responses to accountability requirements: Do we get what we
expect?
AB - BACKGROUND: In health care, accountability is being championed as a promising
approach to meeting the dual imperatives of improving care quality while managing
constrained budgets. PURPOSES: Few studies focus on public sector organizations'
responsiveness to government imperatives for accountability. We applied and
adapted a theory of organizational responsiveness to community care agencies
operating in Ontario, Canada, asking the question: What is the array of realized
organizational responses to government-imposed accountability requirements among
community agencies that receive public funds to provide home and community care?
METHODOLOGY/APPROACH: A sequential complementary mixed methods approach was used.
It gathered data through a survey of 114 home and community care organizations in
Ontario and interviews with 20 key informants representing 13 home and community
care agencies and four government agencies. It generated findings using a
parallel mixed analysis technique. FINDINGS: In addition to responses predicted
by the theory, we found that organizations engage in active, as well as passive,
forms of compliance; we refer to this response as internal modification in which
internal policies, practices, and/or procedures are changed to meet
accountability requirements. We also found that environmental factors, such as
the presence of an association representing organizational interests, can
influence bargaining tactics. PRACTICE IMPLICATIONS: Our study helps us to better
understand the range of likely responses to accountability requirements and is a
first step toward encouraging the development of accountability frameworks that
favor positive outcomes for organizations and those holding them to account.
Tailoring agreements to organizational environments, aligning perceived
compliance with behaviors that encourage improved performance, and allowing for
flexibility in accountability arrangements are suggested strategies to support
beneficial outcomes.
PMID- 26415080
TI - Usefulness of plasma drug monitoring in severe baclofen poisoning.
PMID- 26415081
TI - IL-21-Expressing Mesenchymal Stem Cells Prevent Lethal B-Cell Lymphoma Through
Efficient Delivery of IL-21, Which Redirects the Immune System to Target the
Tumor.
AB - Interleukin (IL)-21, a proinflammatory cytokine, has been developed as an
immunotherapeutic approach due to its effects on various lymphocytes, including
natural killer (NK) cells and T cells; however, the clinical success in cancer
patients has been limited. Recently, mesenchymal stem cells (MSCs) have emerged
as vehicles for cancer gene therapy due to their inherent migratory abilities
toward tumors. In the present study, we hypothesized that MSCs, genetically
modified to express high levels of IL-21 (IL-21/MSCs), can enhance antitumor
responses through localized delivery of IL-21. For tumor induction, BALB/c mice
were injected intravenously with syngeneic A20 B-cell lymphoma cells to develop a
disseminated B-cell lymphoma model. Then, 6 days following tumor induction, the
tumor-bearing mice were treated with IL-21/MSCs weekly, four times. Systemic
infusion of A20 cells led to hind-leg paralysis as well as severe liver
metastasis in the control group. The IL-21/MSC-treated group showed delayed tumor
incidence as well as improved survival, whereas the MSC- and recombinant
adenovirus-expressing IL-21 (rAD/IL-21)-treated groups did not show significant
differences from the untreated mice. These therapeutic effects were associated
with high levels of IL-21 delivered to the liver, which prevented the formation
of tumor nodules. Furthermore, the infusion of IL-21/MSCs led to induction of
effector T and NK cells, while potently inhibiting immune suppressor cells. Our
findings demonstrate that IL-21-expressing MSCs have the therapeutic potential to
induce potent antitumor effects against disseminated B-cell lymphoma through
localized IL-21 delivery and induction of systemic antitumor immunity.
PMID- 26415083
TI - Epindolidione-Based Conjugated Polymers: Synthesis, Electronic Structures, and
Charge Transport Properties.
AB - Development of new electron-deficient building blocks is essential to donor
acceptor conjugated polymers. Herein, epindolidione (EPD) as electron-deficient
unit was integrated into conjugated polymers for the investigation of field
effect transistors for the first time. We systematically studied the electronic
structures and charge transport properties of the EPD-based donor-acceptor
polymers. They exhibit p-type transport characteristics with the highest mobility
of up to 0.40 cm(2) V(-1) s(-1), thus demonstrating its great potential as a
building block for polymer field-effect transistors and photovoltaics.
PMID- 26415082
TI - SCARECROW-LIKE23 and SCARECROW jointly specify endodermal cell fate but
distinctly control SHORT-ROOT movement.
AB - Intercellular signaling through trafficking of regulatory proteins is a
widespread phenomenon in plants and can deliver positional information for the
determination of cell fate. In the Arabidopsis root meristem, the cell fate
determinant SHORT-ROOT (SHR), a GRAS domain transcription factor, acts as a
signaling molecule from the stele to the adjacent layer to specify endodermal
cell fate. Upon exiting the stele, SHR activates another GRAS domain
transcription factor, SCARCROW (SCR), which, together with several
BIRD/INDETERMINATE DOMAIN proteins, restricts movement of SHR to define a single
cell layer of endodermis. Here we report that endodermal cell fate also requires
the joint activity of both SCR and its closest homologue SCARECROW-LIKE23
(SCL23). We show that SCL23 protein moves with zonation-dependent directionality.
Within the meristem, SCL23 exhibits short-ranged movement from ground tissue to
vasculature. Away from the meristem, SCL23 displays long-range rootward movement
into meristematic vasculature and a bidirectional radial spread, respectively. As
a known target of SHR and SCR, SCL23 also interacts with SCR and SHR and can
restrict intercellular outspread of SHR without relying on nuclear retention as
SCR does. Collectively, our data show that SCL23 is a mobile protein that
controls movement of SHR and acts redundantly with SCR to specify endodermal fate
in the root meristem.
PMID- 26415085
TI - Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy.
AB - BACKGROUND: Data on the long-term outcome of children who are exposed to maternal
cancer with or without treatment during pregnancy are lacking. METHODS: In this
multicenter case-control study, we compared children whose mothers received a
diagnosis of cancer during the pregnancy with matched children of women without a
cancer diagnosis. We used a health questionnaire and medical files to collect
data regarding neonatal and general health. All children were prospectively
assessed (by means of a neurologic examination and the Bayley Scales of Infant
Development) at 18 months, 36 months, or both. A cardiac assessment was performed
at 36 months. RESULTS: A total of 129 children (median age, 22 months; range, 12
to 42) were included in the group whose mother had cancer (prenatal-exposure
group) with a matching number in the control group. During pregnancy, 96 children
(74.4%) were exposed to chemotherapy (alone or in combination with other
treatments), 11 (8.5%) to radiotherapy (alone or in combination), 13 (10.1%) to
surgery alone, 2 (1.6%) to other drug treatments, and 14 (10.9%) to no treatment.
Birth weight was below the 10th percentile in 28 of 127 children (22.0%) in the
prenatal-exposure group and in 19 of 125 children (15.2%) in the control group
(P=0.16). There was no significant between-group difference in cognitive
development on the basis of the Bayley score (P=0.08) or in subgroup analyses.
The gestational age at birth was correlated with the cognitive outcome in the two
study groups. Cardiologic evaluation among 47 children at 36 months of age showed
normal cardiac findings. CONCLUSIONS: Prenatal exposure to maternal cancer with
or without treatment did not impair the cognitive, cardiac, or general
development of children in early childhood. Prematurity was correlated with a
worse cognitive outcome, but this effect was independent of cancer treatment.
(Funded by Research Foundation-Flanders and others; ClinicalTrials.gov number,
NCT00330447.).
PMID- 26415084
TI - Treatment of pleural malignancies by photo-induction combined to systemic
chemotherapy: Proof of concept on rodent lung tumors and feasibility study on
porcine chest cavities.
AB - BACKGROUND: Low-dose, Visudyne(r)-mediated photodynamic therapy (photo-induction)
was shown to selectively enhance tumor vessel transport causing increased uptake
of systemically administered chemotherapy in various tumor types grown on rodent
lungs. The present experiments explore the efficacy of photo-induced vessel
modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin(r)) on
rodent lung tumors and the feasibility/toxicity of this approach in porcine chest
cavities. MATERIAL AND METHODS: Three groups of Fischer rats underwent orthotopic
sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation
on the left lung. Half of the animals of each group had photo-induction (0.0625
mg/kg Visudyne(r), 10 J/cm(2) ) followed by IV administration of Lipoplatin(r) (5
mg/kg) and the other half received Lipoplatin(r) without photo-induction. Then,
two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo
induction (0.0625 mg/kg Visudyne(r); 30 J/cm(2) hilum; 10 J/cm(2) apex/diaphragm)
with in situ light dosimetry in combination with IV Lipoplatin(r) administration
(5 mg/kg). Protocol I (n = 6) received Lipoplatin(r) immediately after light
delivery and Protocol II (n = 9) 90 minutes before light delivery. Three
additional animals received Lipoplatin(r) and VATS pleural biopsies but no photo
induction (controls). Lipoplatin(r) concentrations were analyzed in blood and
tissues before and at regular intervals after photo-induction using inductively
coupled plasma mass spectrometry. RESULTS: Photo-induction selectively increased
Lipoplatin(r) uptake in all orthotopic tumors. It significantly increased the
ratio of tumor to lung Lipoplatin(r) concentration in sarcoma (P = 0.0008) and
adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug
application alone. In minipigs, intrapleural photo-induction combined to systemic
Lipoplatin(r) was well tolerated with no toxicity at 7 days for both treatment
protocols. The pleural Lipoplatin(r) concentrations were not significantly
different at 10 and 30 J/cm(2) locations but they were significantly higher in
protocol I compared to II (2.37 +/- 0.7 vs. 1.37 +/- 0.7 ng/mg, P < 0.001).
CONCLUSION: Visudyne(r)-mediated photo-induction selectively enhances the uptake
of IV administered Lipoplatin(r) in rodent lung tumors. Intrapleural VATS photo
induction with identical treatment conditions combined to IV Lipoplatin
chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med.
47:807-816, 2015. (c) 2015 Wiley Periodicals, Inc.
PMID- 26415077
TI - Liver Retransplantation in Patients With HIV-1 Infection: An International
Multicenter Cohort Study.
AB - Liver retransplantation is performed in HIV-infected patients, although its
outcome is not well known. In an international cohort study (eight countries), 37
(6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus
[HBV]) of 600 HIV-infected patients who had undergone liver transplant were
retransplanted. The main indications for retransplantation were vascular
complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV
recurrence (13%). Overall, 19 patients (51%) died after retransplantation.
Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients
with HCV coinfection, HCV RNA replication status at retransplantation was the
only significant prognostic factor. Patients with undetectable versus detectable
HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30%
at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of
death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3,
and 5 years after retransplantation. HIV infection was adequately controlled with
antiretroviral therapy. In conclusion, liver retransplantation is an acceptable
option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV
RNA. Retransplantation in patients with HCV replication should be reassessed
prospectively in the era of new direct antiviral agents.
PMID- 26415086
TI - Cautious Optimism for Offspring of Women with Cancer during Pregnancy.
PMID- 26415088
TI - Sex- and Obesity-specific Association of Aromatase (CYP19A1) Gene Variant with
Apolipoprotein B and Hypertension.
AB - BACKGROUND AND AIMS: Gender differences in cardiovascular disease risk have been
attributed to sex hormones. The CYP19A1 protein (aromatase) plays a critical role
in estrogen biosynthesis and thus affects body fat distribution and regulation.
We examined the relationship between polymorphism of the CYP19A1 gene and
lipoproteins, body mass index (BMI), insulin levels and HOMA index. METHODS:
Randomly selected 2250 Turkish adults (aged 49.7 +/- 11.9 years; 48.6% males)
were genotyped for CYP19A1 rs10046 polymorphism using hybridization probes in
Real-Time PCR LC480 device. RESULTS: Distribution of the CYP19A1 rs10046
polymorphism was 28% (n = 630), 48.3 % (n = 1085) and 23.7% (n = 535) for the CC,
CT and TT genotypes, respectively, and the T allele frequency was 0.48. In
relation to apolipoprotein (apo)B levels, C homozygosity was associated with
higher apoB in non-obese females, contrasting to being so in obese males only,
and further in postmenopausal females. CC genotype in females was associated in
linear regression analysis by 7.2 +/- 3.3 mg/dL higher apoB than CT + TT
genotypes, independent of age and BMI. Among premenopausal females, insulin
levels (p = 0.007), BMI (p = 0.05) and HOMA index (p = 0.034) were higher in C
homozygotes than in T-allele carriers. However, CYP19A1 TT genotype contributed
to hypertension at an OR 1.80 (95% CI 1.12-2.91), independently of age, BMI and
other confounders, in males alone. CONCLUSION: The CYP19A1 rs10046 polymorphism
is associated with cardiovascular risk factors such as circulating apoB, insulin
resistance and hypertension in a sex- and obesity-specific manner.
PMID- 26415089
TI - Do collaborative practical tests encourage student-centered active learning of
gross anatomy?
AB - Benefits of collaborative testing have been identified in many disciplines. This
study sought to determine whether collaborative practical tests encouraged active
learning of anatomy. A gross anatomy course included a collaborative component in
four practical tests. Two hundred and seven students initially completed the test
as individuals and then worked as a team to complete the same test again
immediately afterwards. The relationship between mean individual, team, and
difference (between team and individual) test scores to overall performance on
the final examination (representing overall learning in the course) was examined
using regression analysis. The overall mark in the course increased by 9% with a
decreased failure rate. There was a strong relationship between individual score
and final examination mark (P < 0.001) but no relationship for team score (P =
0.095). A longitudinal analysis showed that the test difference scores increased
after Test 1 which may be indicative of social loafing and this was confirmed by
a significant negative relationship between difference score on Test 4
(indicating a weaker student) and final examination mark (P < 0.001). It appeared
that for this cohort, there was little peer-to-peer learning occurring during the
collaborative testing and that weaker students gained the benefit from team marks
without significant active learning taking place. This negative outcome may be
due to insufficient encouragement of the active learning strategies that were
expected to occur during the collaborative testing process. An improved
understanding of the efficacy of collaborative assessment could be achieved
through the inclusion of questionnaire based data to allow a better
interpretation of learning outcomes. Anat Sci Educ 9: 231-237. (c) 2015 American
Association of Anatomists.
PMID- 26415087
TI - Reactive oxygen species mediate oridonin-induced apoptosis through DNA damage
response and activation of JNK pathway in diffuse large B cell lymphoma.
AB - This study investigated the cytotoxic effect of oridonin (ORI), a diterpenoid
isolated from Rabdosia rubescens, in human diffuse large B cell lymphoma (DLBCL)
in vitro and in vivo and the potential molecular mechanisms for ORI-induced cell
apoptosis. ORI treatment caused reactive oxygen species (ROS)-mediated oxidative
DNA damage response (DDR) and the c-Jun N-terminal kinase (JNK) pathway
activation, leading to an induction of intrinsic apoptosis. ROS abolition blocked
ORI-induced apoptosis and attenuated the expression of phospho-histone H2AX and
phospho-JNK, indicating that ROS-mediated DNA damage and JNK pathway activation
were involved in ORI-induced apoptosis. The systemic administration of ORI
suppressed the growth of human DLBCL xenografts without showing significant
toxicity. These findings suggest that ORI may have promising therapeutic
application in DLBCL.
PMID- 26415090
TI - Capnographic monitoring of midazolam and propofol sedation during ERCP: a
randomized controlled study (EndoBreath Study).
AB - BACKGROUND AND STUDY AIMS: This was to determine whether intervention based on
additional capnographic monitoring reduces the incidence of hypoxemia during
midazolam and propofol sedation for endoscopic retrograde
cholangiopancreatography (ERCP). METHODS: Patients (American Society of
Anesthesiologists [ASA] I - IV) scheduled for ERCP under midazolam and propofol
sedation were randomly assigned to a control arm with standard monitoring or an
interventional arm with additional capnographic monitoring. In both arms
detection of apnea prompted withholding of propofol administration, stimulation
of the patient, insertion of a nasopharyngeal tube, or further measures. The
primary study end point was incidence of hypoxemia (oxygen saturation [Sao 2]
below 90 %); secondary end points included occurrences of severe hypoxemia (Sao 2
<= 85 %), bradycardia, and hypotension, and sedation quality (patient cooperation
and satisfaction). RESULTS: 242 patients were enrolled at three German endoscopy
centers. Intention-to-treat analysis revealed no significant reduction in
hypoxemia incidence in the capnography arm compared with the standard arm (38.0 %
vs. 44.4 %, P = 0.314). Apnea was more frequently detected in the capnography arm
(64.5 % vs. 6.0 %, P < 0.001). There were no differences regarding rates of
bradycardia and hypotension. Per-protocol analysis showed lower incidence of
hypoxemia in the capnography arm compared with the standard arm (31.5 % vs. 44.8
%, P = 0.048). There was one death related to sedation in the standard arm.
Sedation quality was similar in the two groups. CONCLUSION: Intention-to-treat
analysis showed hypoxemia incidence was not significantly lower in the additional
capnography arm compared with standard monitoring. Additional capnographic
monitoring of ventilatory activity resulted in improved detection of apnea.
PMID- 26415091
TI - Direct Capture of Functional Proteins from Mammalian Plasma Membranes into
Nanodiscs.
AB - Mammalian plasma membrane proteins make up the largest class of drug targets yet
are difficult to study in a cell free system because of their intransigent
nature. Herein, we perform direct encapsulation of plasma membrane proteins
derived from mammalian cells into a functional nanodisc library. Peptide
fingerprinting was used to analyze the proteome of the incorporated proteins in
nanodiscs and to further demonstrate that the lipid composition of the nanodiscs
directly affects the class of protein that is incorporated. Furthermore, the
functionality of the incorporated membrane proteome was evaluated by measuring
the activity of membrane proteins: Na(+)/K(+)-ATPase and receptor tyrosine
kinases. This work is the first report of the successful establishment and
characterization of a cell free functional library of mammalian membrane proteins
into nanodiscs.
PMID- 26415092
TI - Large-Scale Assembly of Organic Highly Crystalline Multicomponent Wires through
Surface-Engineered Condensation and Crystallization.
AB - Highly crystalline multicomponent wire arrays are fabricated by a scalable
technique, termed surface-engineered condensation and crystallization (SECC).
Alignment and position are precisely controlled with the guidance of a
micropillar-structured substrate with regionally different wettability and vapor
flow controllability.
PMID- 26415093
TI - Novel methods to optimize the effects of transcranial direct current stimulation:
a systematic review of transcranial direct current stimulation patents.
AB - Transcranial direct current stimulation (tDCS) is a neuromodulatory technique
that has been extensively studied. While there have been initial positive results
in some clinical trials, there is still variability in tDCS results. The aim of
this article is to review and discuss patents assessing novel methods to optimize
the use of tDCS. A systematic review was performed using Google patents database
with tDCS as the main technique, with patents filling date between 2010 and 2015.
Twenty-two patents met our inclusion criteria. These patents attempt to address
current tDCS limitations. Only a few of them have been investigated in clinical
trials (i.e., high-definition tDCS), and indeed most of them have not been tested
before in human trials. Further clinical testing is required to assess which
patents are more likely to optimize the effects of tDCS. We discuss the potential
optimization of tDCS based on these patents and the current experience with
standard tDCS.
PMID- 26415094
TI - Transfer as a function of exploration and stabilization in original practice.
AB - The identification of practice conditions that provide flexibility to perform
successfully in transfer is a long-standing issue in motor learning but is still
not well understood. Here we investigated the hypothesis that a search strategy
that encompasses both exploration and stabilization of the perceptual-motor
workspace will enhance performance in transfer. Twenty-two participants practiced
a virtual projection task (120 trials on each of 3 days) and subsequently
performed two transfer conditions (20 trials/condition) with different
constraints in the angle to project the object. The findings revealed a quadratic
relation between exploration in practice (indexed by autocorrelation and
distribution of error) and subsequent performance error in transfer. The
integration of exploration and stabilization of the perceptual-motor workspace
enhances transfer to tasks with different constraints on the scaling of motor
output.
PMID- 26415095
TI - Acute effects of jaw clenching using a customized mouthguard on anaerobic ability
and ventilatory flows.
AB - The latest findings on the ergogenic effects of a dentistry-design, bite-aligning
mouthpiece require additional research to assess its impact on anaerobic ability
and ventilatory parameters. This paper was aimed at determining the ergogenic
acute effects of wearing a custom-made mouthpiece on oral airflow dynamics, 30-s
Wingate Anaerobic Test performance parameters. Twenty-eight healthy and
physically-active male subjects (age: 24.50 +/- 3.32, height: 181.34 +/- 7.4,
weight: 78.14 +/- 8.21), were voluntarily studied. The subjects were first
briefed on the test protocols, and then performed the 30s Wingate test and
Spirometer test. The experimental trials were performed in a random
counterbalanced order. We evaluate maximum expiratory volume (VEmax L min(-1)),
mean power (W kg(-1)), peak power (W kg(-1)), time to peak (s), rate to fatigue
(Ws(-1)) and lactate production (mMol L(-1)), rate of perceived exertion (RPE).
There were significant differences between mouthguard and no-mouthguard
conditions in mean power (W kg(-1)), peak power (W kg(-1)), time to peak (s), and
rate to fatigue (Ws(-1)) for the 30-s Wingate Anaerobic Test. Significantly lower
lactate production (mMol L(-1)) was observed, in mouthguard condition but no
significant differences were found in RPE. In airflow dynamics, the VEmax L min(
1) was significantly higher when comparing the mouthguard and the no mouthguard
conditions in both forced and unforced conditions. In conclusion, wearing a
customized mouthguard improves anaerobic ability and increases forced expiratory
volume. This study will help practitioners improve athlete's performance in
anaerobic activities where high intensity action might provoke jaw-clenching,
contributing in reductions of lactate and fatigue, and improving ventilatory
parameters.
PMID- 26415096
TI - Single-molecule spectromicroscopy: a route towards sub-wavelength refractometry.
AB - We suggest a novel approach for spatially resolved probing of local fluctuations
of the refractive index n in solids by means of single-molecule (SM)
spectroscopy. It is based on the dependence T1(n) of the effective radiative
lifetime T1 of dye centres in solids on n due to the local-field effects.
Detection of SM zero-phonon lines at low temperatures gives the values of the SM
natural spectral linewidth (which is inversely proportional to T1) and makes it
possible to reveal the distribution of the local n values in solids. Here we
demonstrate this possibility on the example of amorphous polyethylene and
polycrystalline naphthalene doped with terrylene. In particular, we show that the
obtained distributions of lifetime limited spectral linewidths of terrylene
molecules embedded into these matrices are due to the spatial fluctuations of the
refractive index local values.
PMID- 26415097
TI - Mitochondrial Cytochrome c Oxidase Biogenesis Is Regulated by the Redox State of
a Heme-Binding Translational Activator.
AB - AIM: Mitochondrial cytochrome c oxidase (COX), the last enzyme of the respiratory
chain, catalyzes the reduction of oxygen to water and therefore is essential for
cell function and viability. COX is a multimeric complex, whose biogenesis is
extensively regulated. One type of control targets cytochrome c oxidase subunit 1
(Cox1), a key COX enzymatic core subunit translated on mitochondrial ribosomes.
In Saccharomyces cerevisiae, Cox1 synthesis and COX assembly are coordinated
through a negative feedback regulatory loop. This coordination is mediated by
Mss51, a heme-sensing COX1 mRNA-specific processing factor and translational
activator that is also a Cox1 chaperone. In this study, we investigated whether
Mss51 hemylation and Mss51-mediated Cox1 synthesis are both modulated by the
reduction-oxidation (redox) environment. RESULTS: We report that Cox1 synthesis
is attenuated under oxidative stress conditions and have identified one of the
underlying mechanisms. We show that in vitro and in vivo exposure to hydrogen
peroxide induces the formation of a disulfide bond in Mss51 involving CPX motif
heme-coordinating cysteines. Mss51 oxidation results in a heme ligand switch,
thereby lowering heme-binding affinity and promoting its release. We demonstrate
that in addition to affecting Mss51-dependent heme sensing, oxidative stress
compromises Mss51 roles in COX1 mRNA processing and translation. INNOVATION: H2O2
induced downregulation of mitochondrial translation has so far not been reported.
We show that high H2O2 concentrations induce a global attenuation effect, but
milder concentrations specifically affect COX1 mRNA processing and translation in
an Mss51-dependent manner. CONCLUSION: The redox environment modulates Mss51
functions, which are essential for regulation of COX biogenesis and aerobic
energy production.
PMID- 26415098
TI - Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of
Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal
Nephrectomy with No Impact on Kidney Fibrosis.
AB - Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in
many of the cellular processes that underlie progressive kidney fibrosis
including cell proliferation, apoptosis and transforming growth factor beta1
mediated epithelial to mesenchymal transition. We therefore assessed the
therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6
subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold
upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar
rats. Rats undergoing SNx became hypertensive, proteinuric and developed
progressive kidney failure with reduced creatinine clearance. Treatment with the
MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and
prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire
course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria,
glomerular and tubular fibrosis, and alpha-smooth muscle actin expression.
However, inhibition of ERK1/2 activation led to significant compensatory
upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also
increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key
inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of
ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly
due to increased compensatory activation of the p38 and JNK signalling pathways
with subsequent upregulation of PAI-1.
PMID- 26415099
TI - Formation of High-Spin States (S = 3/2 and 2) in Linear Oligo- and
Polyarylamines.
AB - This article describes the study of a linear trimer and three polyarylamines PB1
3 containing a 3,4'-biphenyl ferromagnetic coupler. The synthesis of the model
compound (trimer) and the polymers has been presented. The formation of radical
cations was studied using electrochemical and optical (UV-vis) methods. The
chemical oxidation of these compounds leads to the creation of high-spin states,
evidenced by pulsed EPR nutation spectroscopy. A quartet spin state is observed
for the trimer model compound, and its J exchange coupling constant has been
measured experimentally (J/k = 11.8 K) and compared quantitatively to DFT
calculations. Most importantly, quartet and quintet spin states have been formed
for PB3 and PB2, respectively. These last two doped polymers thus exhibit the
highest spin states observed to date for linear polyarylamine compounds.
PMID- 26415101
TI - Benefits of contingent screening vs primary screening by cell-free DNA testing:
think again.
PMID- 26415100
TI - Chronic fatigue syndrome.
AB - INTRODUCTION: Chronic fatigue syndrome affects between 0.006% and 3% of the
population depending on the criteria of definition used, with women being at
higher risk than men. METHODS AND OUTCOMES: We conducted a systematic overview,
aiming to answer the following clinical question: What are the effects of
selected treatments for chronic fatigue syndrome? We searched: Medline, Embase,
The Cochrane Library, and other important databases up to November 2013 (Clinical
Evidence reviews are updated periodically; please check our website for the most
up-to-date version of this review). RESULTS: At this update, searching of
electronic databases retrieved 169 studies. After deduplication and removal of
conference abstracts, 86 records were screened for inclusion in the overview.
Appraisal of titles and abstracts led to the exclusion of 71 studies and the
further review of 15 full publications. Of the 15 full articles evaluated, two
systematic reviews, one RCT, and one further follow-up report of an RCT were
added at this update. We performed a GRADE evaluation for 23 PICO combinations.
CONCLUSIONS: In this systematic overview, we categorised the effectiveness of
four interventions based on information relating to the effectiveness and safety
of antidepressants, cognitive behavioural therapy, corticosteroids, and graded
exercise therapy.
PMID- 26415102
TI - Systematic transcriptome analysis reveals elevated expression of alcohol
metabolizing genes in NAFLD livers.
AB - Obese animals and non-alcoholic fatty liver disease (NAFLD) patients exhibit
elevated blood alcohol, suggesting potential contributions of alcohol metabolism
to the development of NAFLD. Liver gene expression in patients with biopsy-proven
mild (N = 40) and severe (N = 32) NAFLD were compared to that in healthy liver
donors (N = 7) and alcoholic hepatitis (AH; N = 15) using microarrays. Principal
components analyses (PCA) revealed similar gene expression patterns between mild
and severe NAFLD which clustered with those of AH but were distinct from those of
healthy livers. Differential gene expression between NAFLD and healthy livers was
consistent with established NAFLD-associated genes and NAFLD pathophysiology.
Alcohol-metabolizing enzymes including ADH, ALDH, CYP2E1, and CAT were up
regulated in NAFLD livers. The expression level of alcohol-metabolizing genes in
severe NAFLD was similar to that in AH. The NAFLD gene expression profiles
provide new directions for future investigations to identify disease markers and
targets for prevention and treatment, as well as to foster our understanding of
NAFLD pathogenesis and pathophysiology. Particularly, increased expression of
alcohol-metabolizing genes in NAFLD livers supports a role for endogenous alcohol
metabolism in NAFLD pathology and provides further support for gut microbiome
therapy in NAFLD management. Copyright (c) 2015 Pathological Society of Great
Britain and Ireland. Published by John Wiley (c) Sons, Ltd.
PMID- 26415103
TI - Threshold-Voltage Shifts in Organic Transistors Due to Self-Assembled Monolayers
at the Dielectric: Evidence for Electronic Coupling and Dipolar Effects.
AB - The mechanisms behind the threshold-voltage shift in organic transistors due to
functionalizing of the gate dielectric with self-assembled monolayers (SAMs) are
still under debate. We address the mechanisms by which SAMs determine the
threshold voltage, by analyzing whether the threshold voltage depends on the gate
dielectric capacitance. We have investigated transistors based on five oxide
thicknesses and two SAMs with rather diverse chemical properties, using the
benchmark organic semiconductor dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene.
Unlike several previous studies, we have found that the dependence of the
threshold voltage on the gate-dielectric capacitance is completely different for
the two SAMs. In transistors with an alkyl SAM, the threshold voltage does not
depend on the gate-dielectric capacitance and is determined mainly by the dipolar
character of the SAM, whereas in transistors with a fluoroalkyl SAM the threshold
voltages exhibit a linear dependence on the inverse of the gate-dielectric
capacitance. Kelvin probe force microscopy measurements indicate this behavior is
attributed to an electronic coupling between the fluoroalkyl SAM and the organic
semiconductor.
PMID- 26415104
TI - Prevention of abdominal adhesions and healing skin after peritoniectomy using low
level laser.
AB - BACKGROUND: Adhesions commonly occur after abdominal surgery and can cause bowel
obstruction, chronic abdominal pain, and infertility. Their prevention remains a
challenge. OBJECTIVES: To evaluate the effects of the application of low-level
lasers on the prevention of adhesions and scarring of the skin after
peritoniectomia. METHOD: Twenty-four New Zealand breed male rabbits,
approximately 2 months of age, were randomly divided into 3 groups (n = 8): GC
control group not subjected to laser, GL1-group with laser application at a dose
of 0.2 J, and GL2-group with laser application at a dose of 3.6 J. All animals
received a longitudinal midline incision and a bilateral resection of the
peritoneal fragment, measuring 3 * 1 cm(2) . The animals received a laser
treatment of one application every 24 hours, beginning at the time of surgery and
lasting for a period of 4 days. After 14 days post-surgery, the animals were
killed and adhesion formation was evaluated qualitatively and quantitatively by
means of a laparotomy shaped inverted "U", which allowed for the verification of
the broad wall of the abdominal cavity and organs. Differences were considered
significant at P < 0.05. RESULTS: The adhesion formation was observed in 100% of
the rabbits from groups GC and GL1, as compared to 37.5% of the rabbits from
group GL2 (P < 0.01). The evaluation of the vascularization and tenacity of
adhesions among the groups showed no significant difference. In groups CG and
GL1, 72% and 83% of adhesions were verified between visceras, respectively
whereas in GL2 occurred among abdominal wall. The tensile strength of the skin
between the groups was not significant (P = 0.3106). The resistance of abdominal
wall segments without skin he resistance of skin segments between groups GL2 and
GC were higher than in GL1 (P = 0.01). CONCLUSION: Low-level LASER is effective
in preventing intra-abdominal adhesions in rabbits without compromising strength
and healing of the abdominal wall.
PMID- 26415106
TI - Primary immunodeficiencies and the control of Epstein-Barr virus infection.
AB - Human primary immunodeficiency (PID) states, where mutations in single immune
system genes predispose individuals to certain infectious agents and not others,
are experiments of nature that hold important lessons for the immunologist. The
number of genetically defined PIDs is rising rapidly, as is the opportunity to
learn from them. Epstein-Barr virus (EBV), a human herpesvirus, has long been of
interest because of its complex interaction with the immune system. Thus, it
causes both infectious mononucleosis (IM), an immunopathologic disease associated
with exaggerated host responses, and at least one malignancy, EBV-positive
lymphoproliferative disease, when those responses are impaired. Here, we describe
the full range of PIDs currently linked with an increased risk of EBV-associated
disease. These provide examples where IM-like immunopathology is fatally
exaggerated, and others where responses impaired at the stage of induction,
expansion, or effector function predispose to malignancy. Current evidence from
this rapidly moving field supports the view that lesions in both natural killer
cell and T cell function can lead to EBV pathology.
PMID- 26415105
TI - A Systematic Review of Experimental Strategies Aimed at Improving Motor Function
after Acute and Chronic Spinal Cord Injury.
AB - While various approaches have been proposed in clinical trials aimed at improving
motor function after spinal cord injury in humans, there is still limited
information regarding the scope, methodological quality, and evidence associated
with single-intervention and multi-intervention approaches. A systematic review
performed using the PubMed search engine and the key words "spinal cord injury
motor recovery" identified 1973 records, of which 39 were selected (18 from the
search records and 21 from reference list inspection). Study phase (
clinicaltrials.org criteria) and methodological quality (Cochrane criteria) were
assessed. Studies included proposed a broad range of single-intervention
(encompassing cell therapies, pharmacology, electrical stimulation,
rehabilitation) (encompassing cell therapies, pharmacology, electrical
stimulation, rehabilitation) and multi-intervention approaches (that combined
more than one strategy). The highest evidence level was for Phase III studies
supporting the role of multi-intervention approaches that contained a
rehabilitation component. Quality appraisal revealed that the percentage of
selected studies classified with high risk of bias by Cochrane criteria was as
follows: random sequence generation = 64%; allocation concealment = 77%; blinding
of participants and personnel = 69%; blinding of outcome assessment = 64%;
attrition = 44%; selective reporting = 44%. The current literature contains a
high proportion of studies with a limited ability to measure efficacy in a valid
manner because of low methodological strength in all items of the Cochrane risk
of bias assessment. Recommendations to decrease bias are discussed and include
increased methodological rigor in the study design and recruitment of study
participants, and the use of electrophysiological and imaging measures that can
assess functional integrity of the spinal cord (and may be sufficiently sensitive
to detect changes that occur in response to therapeutic interventions).
PMID- 26415107
TI - Prednisone Use and Risk of Mortality in Patients With Rheumatoid Arthritis:
Moderation by Use of Disease-Modifying Antirheumatic Drugs.
AB - OBJECTIVE: Medications for rheumatoid arthritis (RA) may affect survival.
However, studies often include limited followup and do not account for selection
bias in treatment allocation. Using a large longitudinal database, we examined
the association between prednisone use and mortality in RA, and whether this risk
was modified with concomitant disease-modifying antirheumatic drug (DMARD) use,
after controlling for propensity for treatment with prednisone and individual
DMARDs. METHODS: In a prospective study of 5,626 patients with RA followed for up
to 25 years, we determined the risk of death associated with prednisone use alone
and combined treatment of prednisone with methotrexate (MTX) or sulfasalazine. We
used the random forests method to generate propensity scores for prednisone use
and each DMARD at study entry and during followup. Mortality risks were estimated
using multivariate Cox models that included propensity scores. RESULTS: During
followup (median 4.97 years), 666 patients (11.8%) died. In a multivariate,
propensity-adjusted model, prednisone use was associated with an increased risk
of death (hazard ratio [HR] 2.83 [95% confidence interval (95% CI) 1.03-7.76]).
However, there was a significant interaction between prednisone use and MTX use
(P = 0.03), so that risk was attenuated when patients were treated with both
medications (HR 0.99 [95% CI 0.18-5.36]). However, combination treatment also
weakened the protective association of MTX with mortality. Results were similar
for sulfasalazine. CONCLUSION: Prednisone use was associated with a significantly
increased risk of mortality in patients with RA. This association was mitigated
by concomitant DMARD use, but combined treatment also negated the previously
reported beneficial association of MTX with survival in RA.
PMID- 26415109
TI - Interfacial Donor-Acceptor Engineering of Nanofiber Materials To Achieve
Photoconductivity and Applications.
AB - Self-assembly of pi-conjugate molecules often leads to formation of well-defined
nanofibril structures dominated by the columnar pi-pi stacking between the
molecular planes. These nanofibril materials have drawn increasing interest in
the research frontiers of nanomaterials and nanotechnology, as the nanofibers
demonstrate one-dimensionally enhanced exciton and charge diffusion along the
long axis, and present great potential for varying optoelectronic applications,
such as sensors, optics, photovoltaics, and photocatalysis. However, poor
electrical conductivity remains a technical drawback for these nanomaterials. To
address this problem, we have developed a series of nanofiber structures modified
with different donor-acceptor (D-A) interfaces that are tunable for maximizing
the photoinduced charge separation, thus leading to increase in the electrical
conductivity. The D-A interface can be constructed with covalent linker or
noncovalent interaction (e.g., hydrophobic interdigitation between alkyl chains).
The noncovalent method is generally more flexible for molecular design and
solution processing, making it more adaptable to be applied to other fibril
nanomaterials such as carbon nanotubes. In this Account, we will discuss our
recent discoveries in these research fields, aiming to provide deep insight into
the enabling photoconductivity of nanofibril materials, and the dependence on
interface structure. The photoconductivity generated with the nanofibril material
is proportional to the charge carriers density, which in turn is determined by
the kinetics balance of the three competitive charge transfer processes: (1) the
photoinduced electron transfer from D to A (also referred to as exciton
dissociation), generating majority charge carrier located in the nanofiber; (2)
the back electron transfer; and (3) the charge delocalization along the nanofiber
mediated by the pi-pi stacking interaction. The relative rates of these charge
transfer processes can be tuned by the molecular structure and nanoscale
interface engineering. As a result, maximal photoconductivity can be achieved for
different D-A nanofibril composites. The photoconductive nanomaterials thus
obtained demonstrate unique features and functions when employed in
photochemiresistor sensors, photovoltaics and photocatalysis, all taking
advantages of the large, open interface of nanofibril structure. Upon deposition
onto a substrate, the intertwined nanofibers form networks with porosity in
nanometer scale. The porous structure enables three-dimensional diffusion of
molecules (analytes in sensor or reactants in catalysis), facilitating the
interfacial chemical interactions. For carbon nanotubes, the completely exposed
pi-conjugation facilitates the surface modification through pi-pi stacking in
conjunction with D-A interaction. Depending on the electronic energy levels of D
and A parts, appropriate band alignment can be achieved, thus producing an
electric field across the interface. Presence of such an electric field enhances
the charge separation, which may lead to design of new type of photovoltaic
system using carbon nanotube composite.
PMID- 26415108
TI - Population-specific prognostic models are needed to stratify outcomes for African
Americans with diffuse large B-cell lymphoma.
AB - Diffuse large B-cell lymphoma (DLBCL) demonstrates significant racial differences
in age of onset, stage, and survival. To examine whether population-specific
models improve prediction of outcomes for African-American (AA) patients with
DLBCL, we utilized Surveillance, Epidemiology, and End Results data and compared
stratification by the international prognostic index (IPI) in general and AA
populations. We also constructed and compared prognostic models for general and
AA populations using multivariable logistic regression (LR) and artificial neural
network approaches. While the IPI adequately stratified outcomes for the general
population, it failed to separate AA DLBCL patients into distinct risk groups.
Our AA LR model identified age >= 55 (odds ratio 0.45, [95% CI: 0.36, 0.56], male
sex (0.75, [0.60, 0.93]), and stage III/IV disease (0.43, [0.34, 0.54]) as
adverse predictors of 5-year survival for AA patients. In addition, general
population prognostic models were poorly calibrated for AAs with DLBCL,
indicating a need for validated AA-specific prognostic models.
PMID- 26415110
TI - Towards soft robotic devices for site-specific drug delivery.
AB - Considerable research efforts have recently been dedicated to the establishment
of various drug delivery systems (DDS) that are mechanical/physical, chemical and
biological/molecular DDS. In this paper, we report on the recent advances in site
specific drug delivery (site-specific, controlled, targeted or smart drug
delivery are terms used interchangeably in the literature, to mean to transport a
drug or a therapeutic agent to a desired location within the body and release it
as desired with negligibly small toxicity and side effect compared to classical
drug administration means such as peroral, parenteral, transmucosal, topical and
inhalation) based on mechanical/physical systems consisting of implantable and
robotic drug delivery systems. While we specifically focus on the robotic or
autonomous DDS, which can be reprogrammable and provide multiple doses of a drug
at a required time and rate, we briefly cover the implanted DDS, which are well
developed relative to the robotic DDS, to highlight the design and performance
requirements, and investigate issues associated with the robotic DDS. Critical
research issues associated with both DDSs are presented to describe the research
challenges ahead of us in order to establish soft robotic devices for clinical
and biomedical applications.
PMID- 26415111
TI - Carbon Inverse Opal Rods for Nonenzymatic Cholesterol Detection.
AB - Carbon inverse opal rods made from silica photonic crystal rods are used for
nonenzymatic cholesterol sensing. The characteristic reflection peak originating
from the physical periodic structure works as sensing signals for quantitatively
estimating cholesterol concentrations. Carbon inverse opal rods work both in
cholesterol standard solutions and human serum. They are suitable for practical
use in clinical diagnose.
PMID- 26415112
TI - [Imaging Diagnosis of Ameloblastoma].
PMID- 26415113
TI - PaMiNI-Derived Co-Activation Patterns Indicate Differential Hierarchical Levels
for Two Ventral Visual Areas of the Fusiform Gyrus.
AB - PURPOSE: To investigate the distribution of co-activation patterns of the
recently identified ventral visual areas FG1 and FG2 of the posterior fusiform
gyrus using the novel meta-analytic approach PaMiNI (Pattern Mining in
NeuroImaging). MATERIALS AND METHODS: All neuroimaging experiments reporting
activation foci within FG1 or FG2 were retrieved from the BrainMap database. The
stereotaxic activation foci in standard reference space were analyzed with
PaMiNI. Here, Gaussian mixture modeling was applied to the stereotaxic
coordinates of all foci to identify the underlying brain regions of each dataset.
Then, association analysis was performed to reveal frequent co-activations across
the modeled brain regions. RESULTS: Co-activation patterns of FG1 were mainly
found within the visual system, i.e. in early visual areas, and were
symmetrically distributed across both hemispheres. FG2 features several extra
visual co-activations, mainly to inferior frontal, premotor and parietal regions.
Furthermore, the co-activations of FG2 showed clear lateralization to the left
FG2. CONCLUSION: FG1 shows characteristics of an intermediate visual area between
the early ventral visual cortex and the category-specific higher-order areas. Co
activation patterns of FG2 indicate that FG2 is a higher-order visual area that
probably corresponds to the posterior fusiform face area and partly the visual
word-form area. Key points. Co-activation patterns of areas FG1 and FG2 were
analyzed with PaMiNI. FG1 features mainly symmetric co-activations to areas of
the visual system. FG2 shows several extra-visual co-activations, which are left
lateralized. FG1 corresponds to a hierarchically intermediate, FG2 to a higher
order visual area. The PaMiNI approach is extended to seed-specific mapping of co
activation patterns.
PMID- 26415117
TI - Clinical Characteristics of Sarcoid Arthropathy: A Population-Based Study.
AB - OBJECTIVE: The epidemiology and clinical characteristics of sarcoid arthropathy
are not well described, as only referral-based studies have been reported. This
study aimed to use the data from a geographically well-defined population to
characterize the clinical characteristics of sarcoid arthropathy. METHODS: An
inception cohort of patients with incident sarcoidosis in the years 1976-2013 in
a geographically well-defined population was identified based on comprehensive
individual medical records review. Inclusion required physician diagnosis
supported by histopathology and radiologic features of intrathoracic sarcoidosis,
compatible clinical presentation, and exclusion of other granulomatous diseases.
Patients with joint pain were then identified from this cohort. RESULTS: In 1976
2013, all 345 incident cases of sarcoidosis were identified. Symptoms of joint
pain occurred in 42 patients (mean age 41.2 years, 57.1% female, and 95% white),
and 35 patients had swollen joint(s) on physical examination. Most patients had
arthralgia prior to the diagnosis of sarcoidosis, with an average time to
diagnosis of 21 days. Of the 35 cases, oligoarthritis (2 to 4 joints) was the
most common pattern (88% of cases), followed by monoarthritis (6%) and
polyarthritis (6%). Ankles were involved in 91% of cases. In the majority of
patients (88%), the arthritis resolved within 6 weeks. Classic Lofgren's syndrome
was observed in 11 patients (26%). CONCLUSION: Inflammatory arthritis occurs in a
minority of patients with sarcoidosis. Acute oligoarthritis with bilateral ankle
involvement was the most common pattern of sarcoid arthropathy. It should be
noted that the generalizability of the results may be limited, as the cohort was
predominantly white.
PMID- 26415120
TI - Edible oil structuring: an overview and recent updates.
AB - In recent years, research dealing with edible oil structuring has received
considerable interest from scientific community working in the area of food
formulation. Much of this interest is linked to the possibility of using
structured oil in development of newer product formats with improved nutritional
profile (trans fat-free, low in saturated fats and high in mono and/or poly
unsaturated fatty acids). In addition to the obvious industrial need of finding
the alternative formulation approach, the interesting properties of structured
systems (particularly, oleogels) also makes them a fascinating subject for
fundamental studies. In this paper, we attempt to give a comprehensive and
concise overview of the field of oil structuring with special emphasis on the
updates from recent years. Specifically, several categories of food-grade
oleogelators and their potential food applications are summarized with typical
examples along with a discussion on the general principles and unresolved
challenges related to this emerging area.
PMID- 26415118
TI - Local oxytocin tempers anxiety by activating GABAA receptors in the hypothalamic
paraventricular nucleus.
AB - Oxytocin (Oxt) is released in various hypothalamic and extrahypothalamic brain
areas in response to anxiogenic stimuli to regulate aspects of emotionality and
stress coping. We examined the anxiolytic action of Oxt in the hypothalamic
paraventricular nucleus (PVN) while appraising if Oxt recruits GABA neurons to
inhibit the behavioral, hormonal, and neuronal response to stress in female
prairie voles (Microtus ochrogaster). Voles received an injection of Oxt in the
PVN either before or after an elevated platform stress to determine a time-course
for the effects of Oxt on the hormonal stress response. Subsequently, we
evaluated if ante-stress injections of Oxt affected anxiety-like behaviors as
well as neuronal activity in the PVN, using real-time in-vivo retrodialysis and
immunohistochemistry with c-Fos expression as a biomarker of neural activity. In
addition, we exposed voles to Oxt and a GABAA receptor antagonist, concurrently,
to evaluate the impact of pharmacological blockade of GABAA receptors on the
anxiolytic effects of Oxt. Elevated platform stress amplified anxiety-like
behaviors and hypothalamic-pituitary-adrenal (HPA) axis activity-catalyzing
corticotrophin-releasing hormone (CRH) neuronal activity and augmenting
corticosterone release in circulation. Ante-stress Oxt injections in the PVN
blocked these stress effects while promoting PVN GABA activity and release. Post
stress Oxt treatments were ineffective. The anxiolytic effects of Oxt were
hindered by concurrent pharmacological blockade of GABAA receptors. Together, our
data demonstrate ante-stress treatments of Oxt in the PVN inhibit stress
activation of the HPA axis through recruitment of GABAergic neurons, providing
insights to the local circuitry and potential therapeutically-relevant
mechanisms.
PMID- 26415119
TI - The neurosteroidogenic enzyme 5alpha-reductase modulates the role of D1 dopamine
receptors in rat sensorimotor gating.
AB - Neurosteroids exert diverse modulatory actions on dopamine neurotransmission and
signaling. We previously documented that the enzyme 5alpha-reductase, which
catalyzes the main rate-limiting step in neurosteroid synthesis, is required for
the behavioral responses of Sprague-Dawley rats to non-selective dopaminergic
agonists, such as the D1-D2 receptor agonist apomorphine. Specifically, systemic
and intra-accumbal administrations of the 5alpha-reductase inhibitor finasteride
countered apomorphine-induced deficits of sensorimotor gating, as measured by the
prepulse inhibition (PPI) of the startle reflex; the classes of dopamine
receptors involved in these effects, however, remain unknown. Prior rodent
studies have revealed that the contributions of dopamine receptors to PPI
regulation vary depending on the genetic background; thus, we analyzed the effect
of finasteride on the PPI deficits induced by selective dopamine receptor
agonists in Long-Evans (a strain exhibiting PPI deficits in response to both D1
and D2 receptor agonists) and Sprague-Dawley rats (which display PPI reductions
following treatment with D2, and D3, but not D1 receptor agonists). In Long-Evans
rats, finasteride opposed the PPI deficits induced by activation of D1, but not
D2 receptors; conversely, in Sprague-Dawley rats, finasteride prevented the
reductions in %PPI and accumbal dopamine extracellular levels caused by selective
stimulation of D3, but not D2 receptors; however, the effects on %PPI were not
confirmed by analyses on absolute PPI values. Our findings suggest that 5alpha
reductase modulates the effects of D1, but not D2 receptor agonists on
sensorimotor gating. These data may help elucidate the role of neurosteroids in
neuropsychiatric disorders featuring PPI deficits, including schizophrenia and
Tourette syndrome.
PMID- 26415121
TI - Comparison of Retrograde Intrarenal Surgery and Percutaneous Nephrolithotomy:
From the View of an Anesthesiologist.
AB - PURPOSE: To determine the differences among the hemodynamics, neuroendocrine
stress response (NESR), and postoperative visual analogue scale (VAS) scores of
pain between the procedures of retrograde intrarenal surgery (RIRS) and
percutaneous nephrolithotomy (PNL) for lower pole kidney stones. PATIENTS AND
METHODS: Fifty-six patients undergoing RIRS and PNL with lower puncture approach,
under general anesthesia, were prospectively enrolled in our study. Perioperative
blood pressure (systolic, diastolic, and mean), heart rate, and peripheral oxygen
saturation (SpO2) values were recorded at intervals. Arterial blood gas (ABG) and
blood glucose, serum insulin, and cortisol levels as stress response markers were
analyzed in the perioperative period. Postoperative VAS scores were recorded at
30 minutes and 2, 4, 6, and 12 hours after extubation. Duration of surgery, stone
sizes, and stone-free rates (SFRs) were noted. RESULTS: SFRs were 93.3% in the
PNL group (28/30 patients) and 88.5% in the RIRS group (23/26 patients) (p =
0.52). There was no statistical difference between the hemodynamics of both
groups. Perioperative ABGs and NESRs were similar between groups (p > 0.05).
Postoperative VAS scores and analgesic consumptions were also similar between
groups (p > 0.05). Duration of surgery was significantly shorter in the RIRS
group (p = 0.001). Stone size was significantly higher in the PNL group (p =
0.013). CONCLUSION: Although the PNL is assumed to be more invasive than the RIRS
procedure among urologists and anesthesiologists, both techniques may have
similar perioperative outcomes in terms of hemodynamics, ABG, NESR, and pain
scores in the management of lower pole stones with lower pole approach.
PMID- 26415123
TI - Prediction, simulation, and verification of the phase noise in 80-MHz low-phase
noise crystal oscillators.
AB - To predict the phase noise in an 80-MHz crystal oscillator, on the basis of the
classical Leeson model, we analyzed and selected the oscillator noise figure F
and transistor corner frequency fc reasonably, and then calculated the loaded Q
(QL) value of the oscillator according to the parameters in the selected Butler
oscillation circuit. Thus, we obtained the predicted phase noise in an 80-MHz
crystal oscillator according to the Leeson phase noise formula. Next, the
simulation curve of the phase noise in this 80-MHz low-phase-noise crystal
oscillator was obtained by establishing a transistor nonlinear model using
commercial design software. Then, we debugged the 80-MHz low-phase-noise crystal
oscillator prototype under the guidance of the prediction and simulation results
and tested it. The measured results show that the phase noise predicted after
selecting reasonable parameters for the Leeson model and the ADS simulation curve
of the phase noise obtained by using the nonlinear transistor model are both
close to the actual measured result. This result may be beneficial in simplifying
the design process for low-phase-noise crystal oscillators.
PMID- 26415122
TI - Cross Talk in HEK293 Cells Between Nrf2, HIF, and NF-kappaB Activities upon
Challenges with Redox Therapeutics Characterized with Single-Cell Resolution.
AB - AIM: Many transcription factors with importance in health and disease are redox
regulated. However, how their activities may be intertwined in responses to redox
perturbing stimuli is poorly understood. To enable in-depth characterization of
this aspect, we here developed a methodology for simultaneous determination of
nuclear factor E2-related factor 2 (Nrf2), hypoxia-inducible factor (HIF), and
nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappaB)
activation at single-cell resolution, using a new tool named pTRAF (plasmid for
transcription factor reporter activation based upon fluorescence). The pTRAF
allowed determination of Nrf2, HIF, and NF-kappaB activities in a high-resolution
and high-throughput manner, and we here assessed how redox therapeutics affected
the activities of these transcription factors in human embryonic kidney cells
(HEK293). RESULTS: Cross talk was detected between the three signaling pathways
upon some types of redox therapeutics, also by using inducers typically
considered specific for Nrf2, such as sulforaphane or auranofin, hypoxia for HIF
activation, or tumor necrosis factor alpha (TNFalpha) for NF-kappaB stimulation.
Doxorubicin, at low nontoxic doses, potentiated TNFalpha-induced activation of NF
kappaB and HIF, without effects in stand-alone treatment. Stochastic activation
patterns in cell cultures were also considerable upon challenges with several
redox stimuli. INNOVATION: A novel strategy was here used to study simultaneous
activation of Nrf2, HIF, and NF-kappaB in single cells. The method can also be
adapted for studies of other transcription factors. CONCLUSION: The pTRAF
provides new opportunities for in-depth studies of transcription factor
activities. In this study, we found that upon challenges of cells with several
redox-perturbing conditions, Nrf2, HIF, and NF-kappaB are uniquely responsive to
separate stimuli, but can also display marked cross talk to each other within
single cells. Antioxid. Redox Signal. 26, 229-246.
PMID- 26415124
TI - Development of an ultrasound microscope combined with optical microscope for
multiparametric characterization of a single cell.
AB - Biomechanics of the cell has been gathering much attention because it affects the
pathological status in atherosclerosis and cancer. In the present study, an
ultrasound microscope system combined with optical microscope for
characterization of a single cell with multiple ultrasound parameters was
developed. The central frequency of the transducer was 375 MHz and the scan area
was 80 * 80 MUm with up to 200 * 200 sampling points. An inverted optical
microscope was incorporated in the design of the system, allowing for
simultaneous optical observations of cultured cells. Two-dimensional mapping of
multiple ultrasound parameters, such as sound speed, attenuation, and acoustic
impedance, as well as the thickness, density, and bulk modulus of specimen/cell
under investigation, etc., was realized by the system. Sound speed and thickness
of a 3T3-L1 fibroblast cell were successfully obtained by the system. The
ultrasound microscope system combined with optical microscope further enhances
our understanding of cellular biomechanics.
PMID- 26415125
TI - Dual-frequency acoustic droplet vaporization detection for medical imaging.
AB - Liquid-filled perfluorocarbon droplets emit a unique acoustic signature when
vaporized into gas-filled microbubbles using ultrasound. Here, we conducted a
pilot study in a tissue-mimicking flow phantom to explore the spatial aspects of
droplet vaporization and investigate the effects of applied pressure and droplet
concentration on image contrast and axial and lateral resolution. Control
microbubble contrast agents were used for comparison. A confocal dual-frequency
transducer was used to transmit at 8 MHz and passively receive at 1 MHz. Droplet
signals were of significantly higher energy than microbubble signals. This
resulted in improved signal separation and high contrast-to-tissue ratios (CTR).
Specifically, with a peak negative pressure (PNP) of 450 kPa applied at the
focus, the CTR of B-mode images was 18.3 dB for droplets and -0.4 for
microbubbles. The lateral resolution was dictated by the size of the droplet
activation area, with lower pressures resulting in smaller activation areas and
improved lateral resolution (0.67 mm at 450 kPa). The axial resolution in droplet
images was dictated by the size of the initial droplet and was independent of the
properties of the transmit pulse (3.86 mm at 450 kPa). In post-processing, time
domain averaging (TDA) improved droplet and microbubble signal separation at high
pressures (640 kPa and 700 kPa). Taken together, these results indicate that it
is possible to generate high-sensitivity, high-contrast images of vaporization
events. In the future, this has the potential to be applied in combination with
droplet-mediated therapy to track treatment outcomes or as a standalone
diagnostic system to monitor the physical properties of the surrounding
environment.
PMID- 26415126
TI - Coherent compounding in doppler imaging.
AB - Coherent compounding can provide high frame rates and wide regions of interest
for imaging of blood flow. However, motion will cause out-of-phase summation,
potentially causing image degradation. In this work the impact of blood motion on
SNR and the accuracy of Doppler velocity estimates are investigated. A simplified
model for the compounded Doppler signal is proposed. The model is used to show
that coherent compounding acts as a low-pass filter on the coherent compounding
Doppler signal, resulting in negatively biased velocity estimates. Simulations
and flow phantom experiments are used to quantify the bias and Doppler SNR for
different velocities and beam-to-flow (BTF) angles. It is shown that the bias in
the mean velocity increases with increasing beam-to-flow angle and/or blood
velocity, whereas the SNR decreases; losses up to 4 dB were observed in the
investigated scenarios. Further, a 2-D motion correction scheme is proposed based
on multi-angle vector Doppler velocity estimates. For a velocity of 1.1 v(Nyq)
and a BTF angle of 75 degrees , the bias was reduced from 30% to less than 4% in
simulations. The motion correction scheme was also applied to flow phantom and in
vivo recordings, in both cases resulting in a substantially reduced mean velocity
bias and an SNR less dependent on blood velocity and direction.
PMID- 26415127
TI - Hybrid optoacoustic tomography and pulse-echo ultrasonography using concave
arrays.
AB - Implementation of hybrid imaging using optoacoustic tomography (OAT) and
ultrasound (US) brings together the important advantages and complementary
features of both methods. However, the fundamentally different physical contrast
mechanisms of the two modalities may impose significant difficulties in the
optimal tomographic data acquisition and image formation strategies. We
investigate the applicability of the commonly applied imaging geometries for
acquisition and reconstruction of hybrid optoacoustic tomography and pulse-echo
ultrasound (OPUS) images. Optimization of the ultrasound image formation strategy
using concave array geometry was implemented using a synthetic aperture method
combined with spatial compounding. Experimental validation was performed using a
custom-made multiplexer unit executing switching between the two modalities
employing the same transducer array. A variety of array probes with different
angular coverages were subsequently tested, including arrays for clinical hand
held imaging as well as stationary arrays for tomographic small animal imaging.
The results demonstrate that acquisition of OAT data by mere addition of an
illumination source to the common US linear array geometry may result in
significant limited-view artifacts and overall loss of image quality. On the
other hand, unsatisfactory US image quality is achieved with tomographic arrays
solely optimized for OAT image acquisition without considering the optimal
transmit-receive beamforming parameters. Optimal selection of the array pitch
size, tomographic coverage and spatial compounding parameters has achieved here
an accurate hybrid imaging performance, which was experimentally showcased in
tissuemimicking phantoms, post-mortem mice, and hand-held imaging of a healthy
volunteer. The efficient combination of the two modalities in a single imaging
device reveals the true power of functional and molecular imaging capacities of
OAT in addition to the morphological and functional imaging capabilities of US.
PMID- 26415129
TI - Microbubble-mediated intravascular ultrasound imaging and drug delivery.
AB - Intravascular ultrasound (IVUS) provides radiation-free, real-time imaging and
assessment of atherosclerotic disease in terms of anatomical, functional, and
molecular composition. The primary clinical applications of IVUS imaging include
assessment of luminal plaque volume and real-time image guidance for stent
placement. When paired with microbubble contrast agents, IVUS technology may be
extended to provide nonlinear imaging, molecular imaging, and therapeutic
delivery modes. In this review, we discuss the development of emerging imaging
and therapeutic applications that are enabled by the combination of IVUS imaging
technology and microbubble contrast agents.
PMID- 26415128
TI - Harmonic motion imaging for abdominal tumor detection and high-intensity focused
ultrasound ablation monitoring: an in vivo feasibility study in a transgenic
mouse model of pancreatic cancer.
AB - Harmonic motion imaging (HMI) is a radiationforce- based elasticity imaging
technique that tracks oscillatory tissue displacements induced by sinusoidal
ultrasonic radiation force to assess the resulting oscillatory displacement
denoting the underlying tissue stiffness. The objective of this study was to
evaluate the feasibility of HMI in pancreatic tumor detection and high-intensity
focused ultrasound (HIFU) treatment monitoring. The HMI system consisted of a
focused ultrasound transducer, which generated sinusoidal radiation force to
induce oscillatory tissue motion at 50 Hz, and a diagnostic ultrasound
transducer, which detected the axial tissue displacements based on acquired radio
frequency signals using a 1-D cross-correlation algorithm. For pancreatic tumor
detection, HMI images were generated for pancreatic tumors in transgenic mice and
normal pancreases in wild-type mice. The obtained HMI images showed a high
contrast between normal and malignant pancreases with an average peak-to-peak HMI
displacement ratio of 3.2. Histological analysis showed that no tissue damage was
associated with HMI when it was used for the sole purpose of elasticity imaging.
For pancreatic tumor ablation monitoring, the focused ultrasound transducer was
operated at a higher acoustic power and longer pulse length than that used in
tumor detection to simultaneously induce HIFU thermal ablation and oscillatory
tissue displacements, allowing HMI monitoring without interrupting tumor
ablation. HMI monitoring of HIFU ablation found significant decreases in the peak
to-peak HMI displacements before and after HIFU ablation with a reduction rate
ranging from 15.8% to 57.0%. The formation of thermal lesions after HIFU exposure
was confirmed by histological analysis. This study demonstrated the feasibility
of HMI in abdominal tumor detection and HIFU ablation monitoring.
PMID- 26415130
TI - A 1 kHz A-scan rate pump-probe laser-ultrasound system for robust inspection of
composites.
AB - We recently built a fiber-optic laser-ultrasound (LU) scanner for nondestructive
evaluation (NDE) of aircraft composites and demonstrated its greatly improved
sensitivity and stability compared with current noncontact systems. It is also
very attractive in terms of cost, stability to environmental noise and surface
roughness, simplicity in adjustment, footprint, and flexibility. A new type of a
balanced fiber-optic Sagnac interferometer is a key component of this all-optical
LU pump-probe system. Very high A-scan rates can be achieved because no reference
arm or stabilization feedback are needed. Here, we demonstrate LU system
performance at 1000 A-scans/s combined with a fast 2-D translator operating at a
scanning speed of 100 mm/s with a peak acceleration of 10 m/s(2) in both lateral
directions to produce parallel B-scans at high rates. The fast scanning strategy
is described in detail. The sensitivity of this system, in terms of noise
equivalent pressure, was further improved to be only 8.3 dB above the Nyquist
thermal noise limit. To our knowledge, this is the best reported sensitivity for
a noncontact ultrasonic detector of this dimension used to inspect aircraft
composites.
PMID- 26415131
TI - Design of broadband linear micromachined ultrasonic transducer arrays by means of
boundary element method coupled with normal mode theory.
AB - In view of the maturity of fabrication processes for capacitive micromachined
ultrasonic transducers (cMUTs), engineers and researchers now need efficient and
accurate modeling tools to design linear arrays according to a set of
technological specifications, such as sensitivity, bandwidth, and directivity
pattern. A simplified modeling tool was developed to meet this requirement. It
consists of modeling one element as a set of cMUT columns, each being a 1-D
periodic array of cMUTs. Model description and assessment of simulation results
are given in the first part of the paper. The approach is based on the theory of
linear systems so the output data are linked to input data through a large
matrix, known as an admittance matrix. In the second part of the paper, we
propose reorganization of matrix equations by applying the normal mode theory.
From the modal decomposition, two categories of eigenmodes are highlighted, one
for which all cMUTs vibrate in phase (the fundamental mode) and the others, which
correspond to localized subwavelength resonances, known as baffle modes. The last
part of the paper focuses mainly on the fundamental mode and gives several design
strategies to optimize the frequency response of an element.
PMID- 26415132
TI - Oil saturation effects in lead metaniobate porous piezoceramic: transient
material characteristics.
AB - Lead metaniobate PbNb2O6 (PN) has a unique combination of high piezoelectric
anisotropy; relatively low dielectric permittivity and high Curie temperature;
and a low Q-factor, near 20. The very low Q-factor is the most intriguing PN
property among the piezoelectric materials, and as shown in this research, this
internal high dissipation and damping effect is directly related to the presence
of silicon oil in the porous PN structure; consequently, it is dependent on the
oil properties. To the contrary, the quality factor of PN not saturated with oil
was found to be as high as nearly 400. Full sets of PN electro-mechanical
constants, transient resonance and dissipation characteristics, and their
temperature dependencies were determined under both conditions: PN conventionally
saturated with oil and PN not saturated with oil. As was experimentally shown, at
higher temperatures particularly after a 260 degrees C soak for several days, a
transition from the "with oil" state to the "no oil" state takes place in the
conventional PN properties; this effect is a consequence of the phase transition
in the silicon oil from liquid to solid state.
PMID- 26415133
TI - Unexpected results of non-invasive prenatal testing: are they all so unexpected?
PMID- 26415134
TI - Smartphone-based point-of-care testing of salivary alpha-amylase for personal
psychological measurement.
AB - Here we report a smartphone-based potentiometric biosensor for point-of-care
testing of salivary alpha-amylase (sAA), which is one of the most sensitive
indices of autonomic nervous system activity, and therefore a promising non
invasive biomarker for mental health. The biosensing system includes a smartphone
having a sAA-detection App, a potentiometric reader and a sensing chip with
preloaded reagents. The saliva sample wicks into the reaction zone on the sensing
chip so that the sAA reacts with the preloaded reagents, resulting in conversion
of an electron mediator Fe(CN)6(3-) to Fe(CN)6(4-). The sensing chip is then
pressed by fingers to push the reaction mixture into the detection zone for the
potentiometric measurement. The potential measured by the smartphone-powered
potentiometric reader is sent to the smartphone App via the USB port, and
converted into sAA concentration based on a calibration curve. Using our method,
sAA in real human sample is quantitatively analyzed within 5 min. The results are
in good agreement with that obtained using a reference method, and correlated to
psychological states of the subjects.
PMID- 26415135
TI - Permeability- and Surface-Energy-Tunable Polyurethane Acrylate Molds for
Capillary Force Lithography.
AB - A permeability- and surface-energy-controllable polyurethane acrylate (PUA) mold,
a "capillary-force material (CFM)" mold, is introduced for capillary-force
lithography (CFL). In CFL, the surface energy and gas permeability of the mold
are crucial. However, the modulation of these two main factors at a time is
difficult. Here, we introduce new CFM molds in which the surface energy and
permeability can be modified by controlling the degree of cross-linking of the
CFM. As the degree of cross-linking of the CFM mold increases, the surface energy
and air permeability decrease. The high average functionality of the mold
material makes it possible to produce patterns relatively finely and rapidly due
to the high rate of capillary rise and stiffness, and the low functionality
allows for patterns to form on a curved surface with conformal contact. CFMs with
different functionality and controllable-interfacial properties will extend the
capabilities of capillary force lithography to overcome the geometric limitations
of patterning on a scale below 100 nm and micro- and nanopatterning on the curved
region.
PMID- 26415136
TI - Ablation of porcine ligamentum flavum with Ho:YAG, q-switched Ho:YAG, and
quadrupled Nd:YAG lasers.
AB - BACKGROUND AND OBJECTIVES: Ligamentum flavum (LF) is a tough, rubbery connective
tissue providing a portion of the ligamentous stability to the spinal column, and
in its hypertrophied state forms a significant compressive pathology in
degenerative spinal stenosis. The interaction of lasers and this biological
tissue have not been thoroughly studied. Technological advances improving
endoscopic surgical access to the spinal canal makes selective removal of LF
using small, flexible tools such as laser-coupled fiber optics increasingly
attractive for treatment of debilitating spinal stenosis. Testing was performed
to assess the effect of Ho:YAG, Q-switched Ho:YAG, and frequency quadrupled
Nd:YAG lasers on samples of porcine LF. The objective was to evaluate the
suitability of these lasers for surgical removal of LF. STUDY DESIGN/MATERIALS
AND METHODS: LF was resected from porcine spine within 2 hours of sacrifice and
stored in saline until immediately prior to laser irradiation, which occurred
within an additional 2 hours. The optical absorbance of a sample was measured
over the spectral band from 190 to 2,360 nm both before and after dehydration.
For the experiments using the Ho:YAG (lambda = 2,080 nm, tp = 140 us, FWHM) and
Q-Switched Ho:YAG (lambda = 2,080 nm, tp = 260 ns, FWHM) lasers, energy was
delivered to the LF through a laser-fiber optic with 600 um core and NA = 0.39.
For the experiment using the frequency quadrupled Nd:YAG laser (lambda = 266 nm,
tp = 5 ns FWHM), rather than applying the laser energy through a laser-fiber,
the energy was focused through an aperture and lens directly onto the LF. Five
experiments were conducted to evaluate the effect of the given lasers on LF.
First, using the Ho:YAG laser, the single-pulse laser-hole depth versus laser
fluence was measured with the laser-fiber in direct contact with the LF (1 g
force) and with a standoff distance of 1 mm between the laser-fiber face and the
LF. Second, with the LF remaining in situ and the spine bisected along the
coronal plane, the surface temperature of the LF was measured with an IR camera
during irradiation with the Ho:YAG laser, with and without constant saline flush.
Third, the mass loss was measured over the course of 450 Ho:YAG pulses. Fourth,
hole depth and temperature were measured over 30 pulses of fixed fluence from the
Ho:YAG and Q-Switched Ho:YAG lasers. Fifth, the ablation rate and surface
temperature were measured as a function of fluence from the Nd:YAG laser. Several
LF staining and hole-depth measurement techniques were also explored. RESULTS:
Aside from the expected absorbance peaks corresponding to the water in the LF,
the most significant peaks in absorbance were located in the spectral band from
190 to 290 nm and persisted after the tissue was dehydrated. In the first
experiment, using the Ho:YAG laser and with the laser-fiber in direct contact
with the LF, the lowest single-pulse fluence for which LF was visibly removed was
35 J/cm(2) . Testing was conducted at 6 fluences between 35 and 354 J/cm(2) .
Over this range the single-pulse hole depth was shown to be near linear (R(2) =
0.9374, M = 1.6), ranging from 40 to 639 um (N = 3). For the case where the laser
fiber face was displaced 1 mm from the LF surface, the lowest single-pulse
fluence for which tissue was visibly removed was 72 J/cm(2) . Testing was
conducted at 4 energy densities between 72 and 180 J/cm(2) . Over this range the
single-pulse hole depth was shown to be near linear (R(2) = 0.8951, M = 1.4),
ranging from 31 to 220 um (N = 3). In the second experiment, with LF in situ,
constant flushing with room temperature saline was shown to drastically reduce
surface temperature during exposure to Ho:YAG at 5 Hz with the laser-fiber in
direct contact with the LF. Without saline, over 1 minute of treatment with a per
pulse fluence of 141 mJ/cm(2) , the average maximum surface temperature measured
110 degrees C. With 10 cc's of saline flushed over 1 minute and a per-pulse laser
fluence of 212 mJ/cm(2) , the average maximum surface temperature was 35 degrees
C. In the third experiment, mass loss was shown to be linear over 450 pulses of
600 mJ from the Ho:YAG laser (212 J/cm(2) , direct contact, N = 4; 108 J/cm(2) ,
1 mm standoff, N = 4). With the laser-fiber in direct contact, an average of 53
mg was removed (R(2) = 0.996, M = 0.117) and with 1 mm laser-fiber standoff, an
average of 44 mg was removed (R(2) = 0.9988, M = 0.097). In the fourth
experiment, 30 pulses of the Ho:YAG and Q-Switched Ho:YAG lasers at 1 mm
standoff, and 5 Hz produced similar hole depths for the tested fluences of 9
J/cm(2) (151 and 154 um, respectively) and 18 J/cm(2) (470 and 442 um,
respectively), though the Ho:YAG laser produced significantly more carbonization
around the rim of the laser-hole. The increased carbonization was corroborated by
higher measured LF temperature. In all tests with the Ho:YAG and Q-Switched
Ho:YAG, an audible photo-acoustic affect coincided with the laser pulse. In the
fifth experiment, with the frequency quadrupled Nd:YAG laser at 15 Hz for 450
pulses, ablation depth per pulse was shown to be linear for the fluence range of
0.18 - 0.73 J/cm(2) (R(2) = 0.989, M = 2.4). There was no noticeable photo
acoustic effect nor charring around the rim of the laser-hole. CONCLUSION: The
Ho:YAG, Q-Switched Ho:YAG, and frequency quadrupled Nd:YAG lasers were shown to
remove ligamentum flavum (LF). A single pulse of the Ho:YAG laser was shown to
cause tearing of the tissue and a large zone of necrosis surrounding the laser
hole. Multiple pulses of the Ho:YAG and Q-Switched Ho:YAG lasers caused charring
around the rim of the laser-hole, though the extent of charring was more
extensive with the Ho:YAG laser. Charring caused by the Ho:YAG laser was shown to
be mitigated by continuously flushing the affected LF with saline during
irradiation. The Nd:YAG laser was shown to ablate LF with no gross visible
indication of thermal damage to surrounding LF.
PMID- 26415137
TI - Association of Lupus Anticoagulant With Long-Term Damage Accrual in
Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
AB - OBJECTIVE: Antiphospholipid antibodies (aPL) are frequently present in
antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients;
however, the prognostic impact of aPL in such patients has not been elucidated.
The objective of this study was to determine whether persistent aPL positivity in
AAV patients was associated with increased long-term damage accrual. METHODS:
Clinical data were retrospectively collected on all AAV patients who attended the
vasculitis clinic at our center over a 4-year period. Data collection included
presence of lupus anticoagulant (LAC) and IgG and IgM anticardiolipin (aCL)
antibody titers, along with concurrent diagnosis of antiphospholipid syndrome
(APS). Accumulation of long-term damage was quantified using the Vasculitis
Damage Index (VDI). RESULTS: Data from 116 AAV patients were analyzed. A total of
34% (n = 40) had persistently positive aCL or LAC or a concurrent diagnosis of
APS and were classified as AAV/aPL. A total of 76 patients (66%) were classified
as AAV alone. LAC was present in a statistically higher proportion of AAV/aPL
patients than those in the AAV-alone group (P < 0.0001). Mean VDI score was
significantly higher in the AAV/aPL group at mean +/- SD 3.54 +/- 1.36 as
compared to 1.96 +/- 1.42 in the AAV-alone group (P < 0.0001). Major vascular
damage scores were significantly higher in the AAV/aPL group, with mean +/- SD
0.32 +/- 0.59 as compared to 0.07 +/- 0.26 in the AAV-alone group (P < 0.007).
CONCLUSION: Persistently positive occurrence of aPL, in particular LAC, is
present in a significant proportion of AAV patients and is associated with a
higher VDI score. Clinicians should consider screening AAV patients for aPL.
PMID- 26415138
TI - Meeting Report: "Proteomics from Discovery to Function:" 6th Annual Meeting of
Proteomics Society, India and International Conference-A Milestone for the Indian
Proteomics Community.
AB - Proteomics is at the epicenter of post-genomics biotechnologies that are
currently driving the next generation system science. Moreover, proteomics is a
truly global science. The 6(th) Annual Meeting of Proteomics Society, India (PSI)
and International Conference on "Proteomics from Discovery to Function" held from
December 7-9, 2014, was a transformative endeavor for global proteomics, bringing
together the luminaries in the field of proteomics for the very first time in
India. This meeting report presents the lessons learned and the highlights of
this international scientific conference that was comprised of nine thematic
sessions, pre- and post-conference workshops, and an opportunity to cultivate
enduring collaborations for proteomics science to benefit both India and global
society. The conference had an unforgettable impression on the participants: for
the first time, India hosted past and present President and Council members from
the Human Proteome Organization (HUPO), along with eminent scientists and young
scholars from India and abroad in the field of proteomics at such a large scale,
a major highlight of this international event. In all, the PSI 2014 was a
milestone conference that has firmly poised the Indian life sciences community as
a leading contributor to post-genomics life sciences, thus cultivating crucial
trans-generational capacity and inspiration by recognizing the emerging scholars
and omics systems scientists who can think and conduct science from cell to
society.
PMID- 26415139
TI - A Global Health Diagnostic for Personalized Medicine in Resource-Constrained
World Settings: A Simple PCR-RFLP Method for Genotyping CYP2B6 g.15582C>T and
Science and Policy Relevance for Optimal Use of Antiretroviral Drug Efavirenz.
AB - The use of pharmacogenomics (PGx) knowledge in treatment of individual patients
is becoming a common phenomenon in the developed world. However, poorly resourced
countries have thus far been constrained for three main reasons. First, the cost
of whole genome sequencing is still considerably high in comparison to other (non
genomics) diagnostics in the developing world where both science and social
dynamics create a dynamic and fragile healthcare ecosystem. Second, studies
correlating genomic differences with drug pharmacokinetics and pharmacodynamics
have not been consistent, and more importantly, often not indexed to impact on
societal end-points, beyond clinical practice. Third, ethics regulatory frames
over PGx testing require improvements based on nested accountability systems and
in ways that address the user community needs. Thus, CYP2B6 is a crucial enzyme
in the metabolism of antiretroviral drugs, efavirenz and nevirapine. More than 40
genetic variants have been reported, but only a few contribute to differences in
plasma EFV and NVP concentrations. The most widely reported CYP2B6 variants
affecting plasma drug levels include c.516G>T, c.983T>C, and to a lesser extent,
g.15582C>T, which should be considered in future PGx tests. While the first two
variants are easily characterized, the g.15582C>T detection has been performed
primarily by sequencing, which is costly, labor intensive, and requires access to
barely available expertise in the developing world. We report here on a simple,
practical PCR-RFLP method with vast potentials for use in resource-constrained
world regions to detect the g.15582C>T variation among South African and
Cameroonian persons. The effects of CYP2B6 g.15582C>T on plasma EFV concentration
were further evaluated among HIV/AIDS patients. We report no differences in the
frequency of the g.15582T variant between the South African (0.08) and
Cameroonian (0.06) groups, which are significantly lower than reported in Asians
(0.39) and Caucasians (0.31). The g.15582C/T and T/T genotypes were associated
with significantly reduced EFV levels (p=0.006). This article additionally
presents the policy relevance of the PGX global health diagnostics and therefore,
collectively makes an original interdisciplinary contribution to the field of
integrative biology and personalized medicine in developing world. Such studies
are, in fact, broadly important because resource-constrained regions exist not
only in developing world but also in major geographical parts of the G20 nations
and the developed countries.
PMID- 26415140
TI - CHI3L1 Is a Liver-Enriched, Noninvasive Biomarker That Can Be Used to Stage and
Diagnose Substantial Hepatic Fibrosis.
AB - Liver fibrosis is a major disease that is primarily caused by hepatitis virus
infections, toxins, and alcohol abuse. Diagnosing and staging liver fibrosis are
critical in guiding the treatment of chronic liver diseases, according to several
international and Chinese guidelines. Liver biopsy is the gold standard for
diagnosing and staging liver fibrosis, but it is invasive and suffers from
several limitations. Consequently, much research has focused on the search for a
noninvasive serum biomarker of fibrosis. In this study, we determined that
Chitinase 3-like 1 (CHI3L1) is an abundantly expressed liver gene whose
expression is highly enriched in the liver. We then compared serum levels of
CHI3L1 among patients with various stages of liver fibrosis, as determined by
liver biopsies, and found that the CHI3L1 levels were able to differentiate early
stages of liver fibrosis (S0-S2) from late stages of liver fibrosis (S3-S4). We
further showed that CHI3L1 is a good marker of substantial fibrosis, with areas
under the ROC curves (AUCs) of 0.94 for substantial (S2, S3, S4) fibrosis and
0.96 for advanced (S3, S4) fibrosis. Finally, we showed that CHI3L1 is superior
to hyaluronic acid (HA), type III procollagen (PCIII), laminin (LN), and type IV
collagen (CIV), which are also serum biomarkers of liver fibrosis, in identifying
advanced liver fibrosis in patients with HBV-related liver fibrosis in China.
PMID- 26415141
TI - Clinical utility of postmortem microcomputed tomography of the fetal heart:
diagnostic imaging vs macroscopic dissection.
AB - OBJECTIVES: Congenital cardiac malformations are commonly identified at perinatal
autopsy, which can be challenging in fetuses of early gestation and in macerated
fetuses. Our objective was to examine fetal complex congenital heart disease by
microcomputed tomography (micro-CT), using standard autopsy as the gold standard.
METHODS: In this ethically approved study, ex-vivo isolated fetal heart and fetal
heart-lung blocks underwent iodine preparation prior to micro-CT, and were fixed
in formalin after the micro-CT examination. Images were acquired using a
microfocus-CT scanner with individual specimen image optimization. Twenty-one
indices assessed normally at autopsy were evaluated for each dataset. Cardiac
dissection was performed using a dissecting microscope within 24 h of the micro
CT examination. RESULTS: We examined six fetal hearts, comprising five with
complex congenital cardiac malformations at a gestational age of 17-23 weeks and
an anatomically normal heart of 23 weeks' gestation for reference. All specimens
demonstrated excellent internal contrast at micro-CT examination, and the correct
overall diagnosis was made in all cases. There was agreement for 114/126 indices
assessed on micro-CT and at autopsy dissection (overall concordance of 95.8% (95%
CI, 90.5-98.2%)). Micro-CT was particularly useful in the assessment of
ventricular morphology in macerated fetuses. CONCLUSIONS: Micro-CT of small ex
vivo fetal specimens can provide highly accurate three-dimensional rendering of
complex congenital fetal heart disease. This approach represents a significant
advance in postmortem imaging and confirms the potential of this technology for
non-invasive examination of small fetuses and organs.
PMID- 26415142
TI - 3D Atomic Arrangement at Functional Interfaces Inside Nanoparticles by Resonant
High-Energy X-ray Diffraction.
AB - With current science and technology moving rapidly into smaller scales, nanometer
sized materials, often referred to as NPs, are produced in increasing numbers and
explored for numerous useful applications. Evidence is mounting, however, that
useful properties of NPs can be improved further and even new NP functionality
achieved by not only controlling the NP size and shape but also interfacing
chemically or structurally distinct entities into single, so-called "composite"
NPs. A typical example is core-shell NPs wherein the synergy of distinct atoms at
the core?shell interface endows the NPs with otherwise unachievable
functionality. However, though advantageous, the concept of functional interfaces
inside NPs is still pursued largely by trial-and-error. That is because it is
difficut to assess the interfaces precisely at the atomic level using traditional
experimental techniques and, hence, difficult to take control of. Using the
core?shell interface in less than 10 nm in size Ru core-Pt shells NPs as an
example, we demonstrate that precise knowledge of the 3D atomic arrangement at
functional interfaces inside NPs can be obtained by resonant high-energy X-ray
diffraction (XRD) coupled to element-specific atomic pair distribution function
(PDF) analysis. On the basis of the unique structure knowledge obtained, we
scrutinize the still-debatable influence of core?shell interface on the catalytic
functionality of Ru core-Pt shell NPs, thus evidencing the usefulness of this
nontraditional technique for practical applications.
PMID- 26415144
TI - Percutaneous Renal Access: Surgical Factors Involved in the Acute Reduction of
Renal Function.
AB - INTRODUCTION AND OBJECTIVE: Studies in patients and experimental animals have
shown that percutaneous nephrolithotomy (PCNL) can acutely impair glomerular
filtration and renal perfusion, but the factors contributing to this decline in
renal function are unknown. The present study assessed the contribution of needle
puncture of the kidney vs dilation of the needle tract to the acute decline in
renal hemodynamic and tubular transport function associated with PCNL surgery.
MATERIALS AND METHODS: Acute experiments were performed in three groups of
anesthetized adult farm pigs: sham-percutaneous access (PERC), that is, no
surgical procedure (n = 7); a single-needle stick to access the renal collecting
system (n = 8); expansion of the single-needle access tract with a 30F NephroMax
balloon dilator and insertion of a nephrostomy sheath (n = 10). The glomerular
filtration rate (GFR), effective renal plasma flow (ERPF), and renal extraction
of para-amino hippurate (EPAH, estimates tubular organic anion transporter [OAT]
activity) were assessed before and 1 to 4.5 hours after sham-PERC or PERC
surgical procedures. RESULTS: Overall, GFR responses were similar in all three
groups. Sham-treated PERC pigs showed no significant change in ERPF over the
experimental observation period, whereas a single-needle stick to access the
renal collecting system resulted in renal vasoconstriction (~30% reduction in
ERPF, p < 0.05). Dilation of the single-needle access tract to create the
nephrostomy did not lead to a further decline in ERPF. PERC surgical procedure
mediated renal vasoconstriction was most evident at the 1-hour posttreatment time
point. A reduction in EPAH was only observed in pig kidneys with a nephrostomy.
CONCLUSIONS: Needle puncture of the kidney for percutaneous access to the renal
collecting system is the major driving force for the renal vasoconstriction
observed after PCNL surgery, whereas creation of the nephrostomy appears to be
largely responsible for decreasing tubular OAT activity.
PMID- 26415145
TI - Immunomagnetic Reduction Assay on Des-Gamma-Carboxy Prothrombin for Screening of
Hepatocellular Carcinoma.
AB - The accredited biomarker alpha-fetoprotein (AFP) offers limited sensitivity and
specificity in the early detection of hepatocellular carcinoma (HCC). To improve
the screening performance, des-gamma-carboxy prothrombin (DCP) has been
identified as another promising biomarker of HCC, combined with AFP biomarkers.
The results of the commercial optical enzyme-linked immunosorbent assay (ELISA)
kit easily have the interference problem due to the optical methodology. The
immunomagnetic reduction (IMR) assay based on the magnetic measurement was
utilized to assay DCP biomarkers without the excellent antiinterference
performances. A DCP magnetic reagent, composed of iron-oxide (Fe3O4 ) magnetic
nanoparticles coated with anti-DCP antibodies solved in phosphoryl-buffer
solution, was synthesized and characterized. In the test of standard DCP
antigens, superior antiinterference and sensitivity than optical ELISA were
proved. In the animal test, the results indicate good agreement between the IMR
assay findings and the tumor sizes of HCC rats at all time points after the HCC
implantation. The feasibility of the developed DCP magnetic reagent with the IMR
for the detection of DCP is verified, and demonstrates the high potential for
future clinical applications.
PMID- 26415146
TI - Development and Validation of a High-Fidelity Finite-Element Model of Monopolar
Stimulation in the Implanted Guinea Pig Cochlea.
AB - GOAL: To validate a new electroanatomical model of the implanted guinea pig
cochlea against independently obtained in vivo voltage tomography data, and
evaluate the validity of exist-ing modeling assumptions on current paths and
neural excitation. METHODS: An in silico model was generated from sTSLIM images
and analyzed in COMSOL Multiphysics. Tissue resistivities and boundary conditions
were varied to test model sensitivity. RESULTS: The simulation was most sensitive
to the resistivities of bone, perilymph, and nerve. Bone tissue in particular
should be separated by morphology because different types of bone have different
electrical properties. Despite having a strong impact on intrascalar voltages and
exit pathways, most boundary conditions, including a new alternative proposed to
account for the unmodeled return path, only had a weak effect on neural
excitation. CONCLUSION: The new model demonstrated a strong correlation with the
in vivo voltage data. SIGNIFICANCE: These findings address a long-standing
knowledge gap about appropriate boundary conditions, and will help to promote
wider acceptance of insights from computational models of the cochlea.
PMID- 26415148
TI - Computer-Vision-Assisted Palm Rehabilitation With Supervised Learning.
AB - Physical rehabilitation supported by the computer-assisted-interface is gaining
popularity among health-care fraternity. In this paper, we have proposed a
computer-vision-assisted contactless methodology to facilitate palm and finger
rehabilitation. Leap motion controller has been interfaced with a computing
device to record parameters describing 3-D movements of the palm of a user
undergoing rehabilitation. We have proposed an interface using Unity3D
development platform. Our interface is capable of analyzing intermediate steps of
rehabilitation without the help of an expert, and it can provide online feedback
to the user. Isolated gestures are classified using linear discriminant analysis
(DA) and support vector machines (SVM). Finally, a set of discrete hidden Markov
models (HMM) have been used to classify gesture sequence performed during
rehabilitation. Experimental validation using a large number of samples collected
from healthy volunteers reveals that DA and SVM perform similarly while applied
on isolated gesture recognition. We have compared the results of HMM-based
sequence classification with CRF-based techniques. Our results confirm that both
HMM and CRF perform quite similarly when tested on gesture sequences. The
proposed system can be used for home-based palm or finger rehabilitation in the
absence of experts.
PMID- 26415147
TI - Continuous Cuffless Blood Pressure Estimation Using Pulse Transit Time and
Photoplethysmogram Intensity Ratio.
AB - Pulse transit time (PTT) has attracted much interest for cuffless blood pressure
(BP) measurement. However, its limited accuracy is one of the main problems
preventing its widespread acceptance. Arterial BP oscillates mainly at high
frequency (HF) because of respiratory activity, and at low frequency (LF) because
of vasomotor tone. Prior studies suggested that PTT can track BP variation in HF
range, but was inadequate to follow the LF variation, which is probably the main
reason for its unsatisfactory accuracy. This paper presents a new indicator, the
photoplethysmogram intensity ratio (PIR), which can be affected by changes in the
arterial diameter, and, thus, trace the LF variation of BP. Spectral analysis of
BP, PTT, PIR, and respiratory signal confirmed that PTT was related to BP in HF
at the respiratory frequency, while PIR was associated with BP in LF range. We,
therefore, develop a novel BP estimation algorithm by using both PTT and PIR. The
proposed algorithm was validated on 27 healthy subjects with continuous Finapres
BP as reference. The results showed that the mean +/- standard deviation (SD) for
the estimated systolic, diastolic, and mean BP with the proposed method against
reference were -0.37 +/-5.21, -0.08 +/-4.06, -0.18 +/-4.13 mmHg, and mean
absolute difference (MAD) were 4.09, 3.18, 3.18 mmHg, respectively. Furthermore,
the proposed method outperformed the two most cited PTT algorithms for about 2
mmHg in SD and MAD. These results demonstrated that the proposed BP model using
PIR and PTT can estimate continuous BP with improved accuracy.
PMID- 26415151
TI - Fast Coding of Feature Vectors Using Neighbor-to-Neighbor Search.
AB - Searching for matches to high-dimensional vectors using hard/soft vector
quantization is the most computationally expensive part of various computer
vision algorithms including the bag of visual word (BoW). This paper proposes a
fast computation method, Neighbor-to-Neighbor (NTN) search [1] , which skips some
calculations based on the similarity of input vectors. For example, in image
classification using dense SIFT descriptors, the NTN search seeks similar
descriptors from a point on a grid to an adjacent point. Applications of the NTN
search to vector quantization, a Gaussian mixture model, sparse coding, and a
kernel codebook for extracting image or video representation are presented in
this paper. We evaluated the proposed method on image and video benchmarks: the
PASCAL VOC 2007 Classification Challenge and the TRECVID 2010 Semantic Indexing
Task. NTN-VQ reduced the coding cost by 77.4 percent, and NTN-GMM reduced it by
89.3 percent, without any significant degradation in classification performance.
PMID- 26415150
TI - Connected Filtering on Tree-Based Shape-Spaces.
AB - Connected filters are well-known for their good contour preservation property. A
popular implementation strategy relies on tree-based image representations: for
example, one can compute an attribute characterizing the connected component
represented by each node of the tree and keep only the nodes for which the
attribute is sufficiently high. This operation can be seen as a thresholding of
the tree, seen as a graph whose nodes are weighted by the attribute. Rather than
being satisfied with a mere thresholding, we propose to expand on this idea, and
to apply connected filters on this latest graph. Consequently, the filtering is
performed not in the space of the image, but in the space of shapes built from
the image. Such a processing of shape-space filtering is a generalization of the
existing tree-based connected operators. Indeed, the framework includes the
classical existing connected operators by attributes. It also allows us to
propose a class of novel connected operators from the leveling family, based on
non-increasing attributes. Finally, we also propose a new class of connected
operators that we call morphological shapings. Some illustrations and
quantitative evaluations demonstrate the usefulness and robustness of the
proposed shape-space filters.
PMID- 26415143
TI - Clinical Relevance of Biomarkers of Oxidative Stress.
AB - SIGNIFICANCE: Oxidative stress is considered to be an important component of
various diseases. A vast number of methods have been developed and used in
virtually all diseases to measure the extent and nature of oxidative stress,
ranging from oxidation of DNA to proteins, lipids, and free amino acids. RECENT
ADVANCES: An increased understanding of the biology behind diseases and redox
biology has led to more specific and sensitive tools to measure oxidative stress
markers, which are very diverse and sometimes very low in abundance. CRITICAL
ISSUES: The literature is very heterogeneous. It is often difficult to draw
general conclusions on the significance of oxidative stress biomarkers, as only
in a limited proportion of diseases have a range of different biomarkers been
used, and different biomarkers have been used to study different diseases. In
addition, biomarkers are often measured using nonspecific methods, while specific
methodologies are often too sophisticated or laborious for routine clinical use.
FUTURE DIRECTIONS: Several markers of oxidative stress still represent a viable
biomarker opportunity for clinical use. However, positive findings with currently
used biomarkers still need to be validated in larger sample sizes and compared
with current clinical standards to establish them as clinical diagnostics. It is
important to realize that oxidative stress is a nuanced phenomenon that is
difficult to characterize, and one biomarker is not necessarily better than
others. The vast diversity in oxidative stress between diseases and conditions
has to be taken into account when selecting the most appropriate biomarker.
PMID- 26415152
TI - Hierarchical Spatio-Temporal Probabilistic Graphical Model with Multiple Feature
Fusion for Binary Facial Attribute Classification in Real-World Face Videos.
AB - Recent literature shows that facial attributes, i.e., contextual facial
information, can be beneficial for improving the performance of real-world
applications, such as face verification, face recognition, and image search.
Examples of face attributes include gender, skin color, facial hair, etc. How to
robustly obtain these facial attributes (traits) is still an open problem,
especially in the presence of the challenges of real-world environments: non
uniform illumination conditions, arbitrary occlusions, motion blur and background
clutter. What makes this problem even more difficult is the enormous variability
presented by the same subject, due to arbitrary face scales, head poses, and
facial expressions. In this paper, we focus on the problem of facial trait
classification in real-world face videos. We have developed a fully automatic
hierarchical and probabilistic framework that models the collective set of frame
class distributions and feature spatial information over a video sequence. The
experiments are conducted on a large real-world face video database that we have
collected, labelled and made publicly available. The proposed method is flexible
enough to be applied to any facial classification problem. Experiments on a
large, real-world video database McGillFaces [1] of 18,000 video frames reveal
that the proposed framework outperforms alternative approaches, by up to 16.96
and 10.13%, for the facial attributes of gender and facial hair, respectively.
PMID- 26415149
TI - Real-Time Neuroimaging and Cognitive Monitoring Using Wearable Dry EEG.
AB - GOAL: We present and evaluate a wearable high-density dry-electrode EEG system
and an open-source software framework for online neuroimaging and state
classification. METHODS: The system integrates a 64-channel dry EEG form factor
with wireless data streaming for online analysis. A real-time software framework
is applied, including adaptive artifact rejection, cortical source localization,
multivariate effective connectivity inference, data visualization, and cognitive
state classification from connectivity features using a constrained logistic
regression approach (ProxConn). We evaluate the system identification methods on
simulated 64-channel EEG data. Then, we evaluate system performance, using
ProxConn and a benchmark ERP method, in classifying response errors in nine
subjects using the dry EEG system. RESULTS: Simulations yielded high accuracy
(AUC = 0.97 +/- 0.021) for real-time cortical connectivity estimation. Response
error classification using cortical effective connectivity [short-time direct
directed transfer function (sdDTF)] was significantly above chance with similar
performance (AUC) for cLORETA (0.74 +/-0.09) and LCMV (0.72 +/-0.08) source
localization. Cortical ERP-based classification was equivalent to ProxConn for
cLORETA (0.74 +/-0.16) but significantly better for LCMV (0.82 +/-0.12) .
CONCLUSION: We demonstrated the feasibility for real-time cortical connectivity
analysis and cognitive state classification from high-density wearable dry EEG.
SIGNIFICANCE: This paper is the first validated application of these methods to
64-channel dry EEG. This study addresses a need for robust real-time measurement
and interpretation of complex brain activity in the dynamic environment of the
wearable setting. Such advances can have broad impact in research, medicine, and
brain-computer interfaces. The pipelines are made freely available in the open
source SIFT and BCILAB toolboxes.
PMID- 26415153
TI - Correlated Percolation, Fractal Structures, and Scale-Invariant Distribution of
Clusters in Natural Images.
AB - Natural images are scale invariant with structures at all length scales.We
formulated a geometric view of scale invariance in natural images using
percolation theory, which describes the behavior of connected clusters on
graphs.We map images to the percolation model by defining clusters on a binary
representation for images. We show that critical percolating structures emerge in
natural images and study their scaling properties by identifying fractal
dimensions and exponents for the scale-invariant distributions of clusters. This
formulation leads to a method for identifying clusters in images from underlying
structures as a starting point for image segmentation.
PMID- 26415154
TI - Labeled Graph Kernel for Behavior Analysis.
AB - Automatic behavior analysis from video is a major topic in many areas of
research, including computer vision, multimedia, robotics, biology, cognitive
science, social psychology, psychiatry, and linguistics. Two major problems are
of interest when analyzing behavior. First, we wish to automatically categorize
observed behaviors into a discrete set of classes (i.e., classification). For
example, to determine word production from video sequences in sign language.
Second, we wish to understand the relevance of each behavioral feature in
achieving this classification (i.e., decoding). For instance, to know which
behavior variables are used to discriminate between the words apple and onion in
American Sign Language (ASL). The present paper proposes to model behavior using
a labeled graph, where the nodes define behavioral features and the edges are
labels specifying their order (e.g., before, overlaps, start). In this approach,
classification reduces to a simple labeled graph matching. Unfortunately, the
complexity of labeled graph matching grows exponentially with the number of
categories we wish to represent. Here, we derive a graph kernel to quickly and
accurately compute this graph similarity. This approach is very general and can
be plugged into any kernel-based classifier. Specifically, we derive a Labeled
Graph Support Vector Machine (LGSVM) and a Labeled Graph Logistic Regressor
(LGLR) that can be readily employed to discriminate between many actions (e.g.,
sign language concepts). The derived approach can be readily used for decoding
too, yielding invaluable information for the understanding of a problem (e.g., to
know how to teach a sign language). The derived algorithms allow us to achieve
higher accuracy results than those of state-of-the-art algorithms in a fraction
of the time. We show experimental results on a variety of problems and datasets,
including multimodal data.
PMID- 26415155
TI - Supervised Evaluation of Image Segmentation and Object Proposal Techniques.
AB - This paper tackles the supervised evaluation of image segmentation and object
proposal algorithms. It surveys, structures, and deduplicates the measures used
to compare both segmentation results and object proposals with a ground truth
database; and proposes a new measure: the precision-recall for objects and parts.
To compare the quality of these measures, eight state-of-the-art object proposal
techniques are analyzed and two quantitative meta-measures involving nine state
of the art segmentation methods are presented. The meta-measures consist in
assuming some plausible hypotheses about the results and assessing how well each
measure reflects these hypotheses. As a conclusion of the performed experiments,
this paper proposes the tandem of precision-recall curves for boundaries and for
objects-and-parts as the tool of choice for the supervised evaluation of image
segmentation. We make the datasets and code of all the measures publicly
available.
PMID- 26415156
TI - The Information Available to a Moving Observer on Shape with Unknown, Isotropic
BRDFs.
AB - Psychophysical studies show motion cues inform about shape even with unknown
reflectance. Recent works in computer vision have considered shape recovery for
an object of unknown BRDF using light source or object motions. This paper
proposes a theory that addresses the remaining problem of determining shape from
the (small or differential) motion of the camera, for unknown isotropic BRDFs.
Our theory derives a differential stereo relation that relates camera motion to
surface depth, which generalizes traditional Lambertian assumptions. Under
orthographic projection, we show differential stereo may not determine shape for
general BRDFs, but suffices to yield an invariant for several restricted (still
unknown) BRDFs exhibited by common materials. For the perspective case, we show
that differential stereo yields the surface depth for unknown isotropic BRDF and
unknown directional lighting, while additional constraints are obtained with
restrictions on the BRDF or lighting. The limits imposed by our theory are
intrinsic to the shape recovery problem and independent of choice of
reconstruction method. We also illustrate trends shared by theories on shape from
differential motion of light source, object or camera, to relate the hardness of
surface reconstruction to the complexity of imaging setup.
PMID- 26415157
TI - Learning to Deblur.
AB - We describe a learning-based approach to blind image deconvolution. It uses a
deep layered architecture, parts of which are borrowed from recent work on neural
network learning, and parts of which incorporate computations that are specific
to image deconvolution. The system is trained end-to-end on a set of artificially
generated training examples, enabling competitive performance in blind
deconvolution, both with respect to quality and runtime.
PMID- 26415158
TI - Uncertain LDA: Including Observation Uncertainties in Discriminative Transforms.
AB - Linear discriminant analysis (LDA) is a powerful technique in pattern recognition
to reduce the dimensionality of data vectors. It maximizes discriminability by
retaining only those directions that minimize the ratio of within-class and
between-class variance. In this paper, using the same principles as for
conventional LDA, we propose to employ uncertainties of the noisy or distorted
input data in order to estimate maximally discriminant directions. We demonstrate
the efficiency of the proposed uncertain LDA on two applications using state-of
the-art techniques. First, we experiment with an automatic speech recognition
task, in which the uncertainty of observations is imposed by real-world additive
noise. Next, we examine a full-scale speaker recognition system, considering the
utterance duration as the source of uncertainty in authenticating a speaker. The
experimental results show that when employing an appropriate uncertainty
estimation algorithm, uncertain LDA outperforms its conventional LDA counterpart.
PMID- 26415159
TI - WordlePlus: Expanding Wordle's Use through Natural Interaction and Animation.
AB - Wordle has been commonly used to summarize texts, with each word size-coded by
its frequency of occurrences--the more often a word occurs in texts, the bigger
it is. The interactive authoring tool WordlePlus leverages natural interaction
and animation to give users more control over wordle development. WordlePlus
supports direct manipulation of words with pen and touch interaction. It
introduces two-word multitouch manipulation, such as concatenating and grouping
two words, and provides pen interaction for adding and deleting words. In
addition, WordlePlus employs animation to help users create more dynamic and
engaging wordles.
PMID- 26415160
TI - Angle-Preserving Quadrilateral Mesh Parameterization.
AB - In response to their growing use in the real world, this article presents two
algorithms for direct parameterization of quadrilateral meshes. The proposed
algorithms are angle-preserving mappings, with one mapping a topological disk
surface onto a Euclidean plane and one mapping a topological sphere surface onto
a unit sphere. Specifically, for topological disk surfaces, the authors devise a
discrete conformal energy function to flatten the quadrilateral meshes with a
length-preserving boundary condition. For topological sphere surfaces, a derived
Tuette energy function is applied to the initialization of parameterization for a
mesh, and then the final spherical parametrization result is obtained by
minimizing a devised harmonic energy function. Experimental results demonstrate
the efficiency of the proposed methods.
PMID- 26415161
TI - Key-Node-Separated Graph Clustering and Layouts for Human Relationship Graph
Visualization.
AB - Many graph-drawing methods apply node-clustering techniques based on the density
of edges to find tightly connected subgraphs and then hierarchically visualize
the clustered graphs. However, users may want to focus on important nodes and
their connections to groups of other nodes for some applications. For this
purpose, it is effective to separately visualize the key nodes detected based on
adjacency and attributes of the nodes. This article presents a graph
visualization technique for attribute-embedded graphs that applies a graph
clustering algorithm that accounts for the combination of connections and
attributes. The graph clustering step divides the nodes according to the
commonality of connected nodes and similarity of feature value vectors. It then
calculates the distances between arbitrary pairs of clusters according to the
number of connecting edges and the similarity of feature value vectors and
finally places the clusters based on the distances. Consequently, the technique
separates important nodes that have connections to multiple large clusters and
improves the visibility of such nodes' connections. To test this technique, this
article presents examples with human relationship graph datasets, including a
coauthorship and Twitter communication network dataset.
PMID- 26415162
TI - A Comparison of Health Visualization Evaluation Techniques with Older Adults.
AB - Aging-associated changes in visual acuity, cognition, and motor control in
addition to attitudinal and affective perceptions of technology impact the design
of information systems for older adults. Although design guidelines and cognitive
theories on information visualization exist, they are often understudied for use
with older adults. In an effort to evaluate interactive health visualizations
with older adults, the authors applied and compared a benchmark evaluation, an
insight-based evaluation, and a subjective usability questionnaire. They were
unable to identify statistically significant differences between visualizations
using the benchmark evaluation, but found moderate differences with the perceived
usability scale and more granular differences through the insight evaluation.
PMID- 26415163
TI - ENTVis: A Visual Analytic Tool for Entropy-Based Network Traffic Anomaly
Detection.
AB - Entropy-based traffic metrics have received substantial attention in network
traffic anomaly detection because entropy can provide fine-grained metrics of
traffic distribution characteristics. However, some practical issues--such as
ambiguity, lack of detailed distribution information, and a large number of false
positives--affect the application of entropy-based traffic anomaly detection. In
this work, we introduce a visual analytic tool called ENTVis to help users
understand entropy-based traffic metrics and achieve accurate traffic anomaly
detection. ENTVis provides three coordinated views and rich interactions to
support a coherent visual analysis on multiple perspectives: the timeline group
view for perceiving situations and finding hints of anomalies, the Radviz view
for clustering similar anomalies in a period, and the matrix view for
understanding traffic distributions and diagnosing anomalies in detail. Several
case studies have been performed to verify the usability and effectiveness of our
method. A further evaluation was conducted via expert review.
PMID- 26415164
TI - Body Composition Assessment in Axial CT Images Using FEM-Based Automatic
Segmentation of Skeletal Muscle.
AB - The proportions of muscle and fat tissues in the human body, referred to as body
composition is a vital measurement for cancer patients. Body composition has been
recently linked to patient survival and the onset/recurrence of several types of
cancers in numerous cancer research studies. This paper introduces a fully
automatic framework for the segmentation of muscle and fat tissues from CT images
to estimate body composition. We developed a novel finite element method (FEM)
deformable model that incorporates a priori shape information via a statistical
deformation model (SDM) within the template-based segmentation framework. The
proposed method was validated on 1000 abdominal and 530 thoracic CT images and we
obtained very good segmentation results with Jaccard scores in excess of 90% for
both the muscle and fat regions.
PMID- 26415165
TI - Unifying Concepts of Statistical and Spectral Quantitative Ultrasound Techniques.
AB - Quantitative ultrasound (QUS) techniques using radiofrequency (RF) backscattered
signals have been used for tissue characterization of numerous organ systems. One
approach is to use the magnitude and frequency dependence of backscatter echoes
to quantify tissue structures. Another approach is to use first-order statistical
properties of the echo envelope as a signature of the tissue microstructure. We
propose a unification of these QUS concepts. For this purpose, a mixture of
homodyned K-distributions is introduced to model the echo envelope, together with
an estimation method and a physical interpretation of its parameters based on the
echo signal spectrum. In particular, the total, coherent and diffuse signal
powers related to the proposed mixture model are expressed explicitly in terms of
the structure factor previously studied to describe the backscatter coefficient
(BSC). Then, this approach is illustrated in the context of red blood cell (RBC)
aggregation. It is experimentally shown that the total, coherent and diffuse
signal powers are determined by a structural parameter of the spectral Structure
Factor Size and Attenuation Estimator. A two-way repeated measures ANOVA test
showed that attenuation (p-value of 0.077) and attenuation compensation (p-value
of 0.527) had no significant effect on the diffuse to total power ratio. These
results constitute a further step in understanding the physical meaning of first
order statistics of ultrasound images and their relations to QUS techniques. The
proposed unifying concepts should be applicable to other biological tissues than
blood considering that the structure factor can theoretically model any spatial
distribution of scatterers.
PMID- 26415166
TI - Stable Overlapping Replicator Dynamics for Brain Community Detection.
AB - A fundamental means for understanding the brain's organizational structure is to
group its spatially disparate regions into functional subnetworks based on their
interactions. Most community detection techniques are designed for generating
partitions, but certain brain regions are known to interact with multiple
subnetworks. Thus, the brain's underlying subnetworks necessarily overlap. In
this paper, we propose a technique for identifying overlapping subnetworks from
weighted graphs with statistical control over false node inclusion. Our technique
improves upon the replicator dynamics formulation by incorporating a graph
augmentation strategy to enable subnetwork overlaps, and a graph incrementation
scheme for merging subnetworks that might be falsely split by replicator dynamics
due to its stringent mutual similarity criterion in defining subnetworks. To
statistically control for inclusion of false nodes into the detected subnetworks,
we further present a procedure for integrating stability selection into our
subnetwork identification technique. We refer to the resulting technique as
stable overlapping replicator dynamics (SORD). Our experiments on synthetic data
show significantly higher accuracy in subnetwork identification with SORD than
several state-of-the-art techniques. We also demonstrate higher test-retest
reliability in multiple network measures on the Human Connectome Project data.
Further, we illustrate that SORD enables identification of neuroanatomically
meaningful subnetworks and network hubs.
PMID- 26415167
TI - An Automatic Learning-Based Framework for Robust Nucleus Segmentation.
AB - Computer-aided image analysis of histopathology specimens could potentially
provide support for early detection and improved characterization of diseases
such as brain tumor, pancreatic neuroendocrine tumor (NET), and breast cancer.
Automated nucleus segmentation is a prerequisite for various quantitative
analyses including automatic morphological feature computation. However, it
remains to be a challenging problem due to the complex nature of histopathology
images. In this paper, we propose a learning-based framework for robust and
automatic nucleus segmentation with shape preservation. Given a nucleus image, it
begins with a deep convolutional neural network (CNN) model to generate a
probability map, on which an iterative region merging approach is performed for
shape initializations. Next, a novel segmentation algorithm is exploited to
separate individual nuclei combining a robust selection-based sparse shape model
and a local repulsive deformable model. One of the significant benefits of the
proposed framework is that it is applicable to different staining histopathology
images. Due to the feature learning characteristic of the deep CNN and the high
level shape prior modeling, the proposed method is general enough to perform well
across multiple scenarios. We have tested the proposed algorithm on three large
scale pathology image datasets using a range of different tissue and stain
preparations, and the comparative experiments with recent state of the arts
demonstrate the superior performance of the proposed approach.
PMID- 26415168
TI - DASH-N: Joint Hierarchical Domain Adaptation and Feature Learning.
AB - Complex visual data contain discriminative structures that are difficult to be
fully captured by any single feature descriptor. While recent work on domain
adaptation focuses on adapting a single hand-crafted feature, it is important to
perform adaptation of a hierarchy of features to exploit the richness of visual
data. We propose a novel framework for domain adaptation using a sparse and
hierarchical network (DASH-N). Our method jointly learns a hierarchy of features
together with transformations that rectify the mismatch between different
domains. The building block of DASH-N is the latent sparse representation. It
employs a dimensionality reduction step that can prevent the data dimension from
increasing too fast as one traverses deeper into the hierarchy. The experimental
results show that our method compares favorably with the competing state-of-the
art methods. In addition, it is shown that a multi-layer DASH-N performs better
than a single-layer DASH-N.
PMID- 26415169
TI - MToS: A Tree of Shapes for Multivariate Images.
AB - The topographic map of a gray-level image, also called tree of shapes, provides a
high-level hierarchical representation of the image contents. This
representation, invariant to contrast changes and to contrast inversion, has been
proved very useful to achieve many image processing and pattern recognition
tasks. Its definition relies on the total ordering of pixel values, so this
representation does not exist for color images, or more generally, multivariate
images. Common workarounds, such as marginal processing, or imposing a total
order on data, are not satisfactory and yield many problems. This paper presents
a method to build a tree-based representation of multivariate images, which
features marginally the same properties of the gray-level tree of shapes. Briefly
put, we do not impose an arbitrary ordering on values, but we only rely on the
inclusion relationship between shapes in the image definition domain. The
interest of having a contrast invariant and self-dual representation of
multivariate image is illustrated through several applications (filtering,
segmentation, and object recognition) on different types of data: color natural
images, document images, satellite hyperspectral imaging, multimodal medical
imaging, and videos.
PMID- 26415170
TI - Compressed image quality metric based on perceptually weighted distortion.
AB - Objective quality assessment for compressed images is critical to various image
compression systems that are essential in image delivery and storage. Although
the mean squared error (MSE) is computationally simple, it may not be accurate to
reflect the perceptual quality of compressed images, which is also affected
dramatically by the characteristics of human visual system (HVS), such as masking
effect. In this paper, an image quality metric (IQM) is proposed based on
perceptually weighted distortion in terms of the MSE. To capture the
characteristics of HVS, a randomness map is proposed to measure the masking
effect and a preprocessing scheme is proposed to simulate the processing that
occurs in the initial part of HVS. Since the masking effect highly depends on the
structural randomness, the prediction error from neighborhood with a statistical
model is used to measure the significance of masking. Meanwhile, the
imperceptible signal with high frequency could be removed by preprocessing with
low-pass filters. The relation is investigated between the distortions before and
after masking effect, and a masking modulation model is proposed to simulate the
masking effect after preprocessing. The performance of the proposed IQM is
validated on six image databases with various compression distortions. The
experimental results show that the proposed algorithm outperforms other benchmark
IQMs.
PMID- 26415171
TI - Layered compression for high-precision depth data.
AB - With the development of depth data acquisition technologies, access to high
precision depth with more than 8-b depths has become much easier and determining
how to efficiently represent and compress high-precision depth is essential for
practical depth storage and transmission systems. In this paper, we propose a
layered high-precision depth compression framework based on an 8-b image/video
encoder to achieve efficient compression with low complexity. Within this
framework, considering the characteristics of the high-precision depth, a depth
map is partitioned into two layers: 1) the most significant bits (MSBs) layer and
2) the least significant bits (LSBs) layer. The MSBs layer provides rough depth
value distribution, while the LSBs layer records the details of the depth value
variation. For the MSBs layer, an error-controllable pixel domain encoding scheme
is proposed to exploit the data correlation of the general depth information with
sharp edges and to guarantee the data format of LSBs layer is 8 b after taking
the quantization error from MSBs layer. For the LSBs layer, standard 8-b
image/video codec is leveraged to perform the compression. The experimental
results demonstrate that the proposed coding scheme can achieve real-time depth
compression with satisfactory reconstruction quality. Moreover, the compressed
depth data generated from this scheme can achieve better performance in view
synthesis and gesture recognition applications compared with the conventional
coding schemes because of the error control algorithm.
PMID- 26415172
TI - Joint Sparse Representation and Robust Feature-Level Fusion for Multi-Cue Visual
Tracking.
AB - Visual tracking using multiple features has been proved as a robust approach
because features could complement each other. Since different types of variations
such as illumination, occlusion, and pose may occur in a video sequence,
especially long sequence videos, how to properly select and fuse appropriate
features has become one of the key problems in this approach. To address this
issue, this paper proposes a new joint sparse representation model for robust
feature-level fusion. The proposed method dynamically removes unreliable features
to be fused for tracking by using the advantages of sparse representation. In
order to capture the non-linear similarity of features, we extend the proposed
method into a general kernelized framework, which is able to perform feature
fusion on various kernel spaces. As a result, robust tracking performance is
obtained. Both the qualitative and quantitative experimental results on publicly
available videos show that the proposed method outperforms both sparse
representation-based and fusion based-trackers.
PMID- 26415173
TI - Automatic Liver Segmentation Based on Shape Constraints and Deformable Graph Cut
in CT Images.
AB - Liver segmentation is still a challenging task in medical image processing area
due to the complexity of the liver's anatomy, low contrast with adjacent organs,
and presence of pathologies. This investigation was used to develop and validate
an automated method to segment livers in CT images. The proposed framework
consists of three steps: 1) preprocessing; 2) initialization; and 3)
segmentation. In the first step, a statistical shape model is constructed based
on the principal component analysis and the input image is smoothed using
curvature anisotropic diffusion filtering. In the second step, the mean shape
model is moved using thresholding and Euclidean distance transformation to obtain
a coarse position in a test image, and then the initial mesh is locally and
iteratively deformed to the coarse boundary, which is constrained to stay close
to a subspace of shapes describing the anatomical variability. Finally, in order
to accurately detect the liver surface, deformable graph cut was proposed, which
effectively integrates the properties and inter-relationship of the input images
and initialized surface. The proposed method was evaluated on 50 CT scan images,
which are publicly available in two databases Sliver07 and 3Dircadb. The
experimental results showed that the proposed method was effective and accurate
for detection of the liver surface.
PMID- 26415174
TI - Cost-Sensitive Local Binary Feature Learning for Facial Age Estimation.
AB - In this paper, we propose a cost-sensitive local binary feature learning (CS
LBFL) method for facial age estimation. Unlike the conventional facial age
estimation methods that employ hand-crafted descriptors or holistically learned
descriptors for feature representation, our CS-LBFL method learns discriminative
local features directly from raw pixels for face representation. Motivated by the
fact that facial age estimation is a cost-sensitive computer vision problem and
local binary features are more robust to illumination and expression variations
than holistic features, we learn a series of hashing functions to project raw
pixel values extracted from face patches into low-dimensional binary codes, where
binary codes with similar chronological ages are projected as close as possible,
and those with dissimilar chronological ages are projected as far as possible.
Then, we pool and encode these local binary codes within each face image as a
real-valued histogram feature for face representation. Moreover, we propose a
cost-sensitive local binary multi-feature learning method to jointly learn
multiple sets of hashing functions using face patches extracted from different
scales to exploit complementary information. Our methods achieve competitive
performance on four widely used face aging data sets.
PMID- 26415175
TI - Transforms for Intra Prediction Residuals Based on Prediction Inaccuracy
Modeling.
AB - In intra video coding and image coding, the directional intra prediction is used
to reduce spatial redundancy. Intra prediction residuals are encoded with
transforms. In this paper, we develop transforms for directional intra prediction
residuals. In particular, we observe that the directional intra prediction is
most effective in smooth regions and edges with a particular direction. In the
ideal case, edges can be predicted fairly accurately with an accurate prediction
direction. In practice, an accurate prediction direction is hard to obtain. Based
on the inaccuracy of prediction direction that arises in the design of many
practical video coding systems, we can estimate the residual covariance and
propose a class of transforms based on the estimated covariance function. The
proposed method is evaluated by the energy compaction property. The experimental
results show that, with the proposed method, the same amount of energy in
directional intra prediction residuals can be preserved with a significantly
smaller number of transform coefficients.
PMID- 26415176
TI - Common Visual Pattern Discovery via Nonlinear Mean Shift Clustering.
AB - Discovering common visual patterns (CVPs) from two images is a challenging task
due to the geometric and photometric deformations as well as noises and clutters.
The problem is generally boiled down to recovering correspondences of local
invariant features, and the conventionally addressed by graph-based quadratic
optimization approaches, which often suffer from high computational cost. In this
paper, we propose an efficient approach by viewing the problem from a novel
perspective. In particular, we consider each CVP as a common object in two images
with a group of coherently deformed local regions. A geometric space with matrix
Lie group structure is constructed by stacking up transformations estimated from
initially appearance-matched local interest region pairs. This is followed by a
mean shift clustering stage to group together those close transformations in the
space. Joining regions associated with transformations of the same group together
within each input image forms two large regions sharing similar geometric
configuration, which naturally leads to a CVP. To account for the non-Euclidean
nature of the matrix Lie group, mean shift vectors are derived in the
corresponding Lie algebra vector space with a newly provided effective distance
measure. Extensive experiments on single and multiple common object discovery
tasks as well as near-duplicate image retrieval verify the robustness and
efficiency of the proposed approach.
PMID- 26415177
TI - Robust Matching Cost Function for Stereo Correspondence Using Matching by Tone
Mapping and Adaptive Orthogonal Integral Image.
AB - Real-world stereo images are inevitably affected by radiometric differences,
including variations in exposure, vignetting, lighting, and noise. Stereo images
with severe radiometric distortion can have large radiometric differences and
include locally nonlinear changes. In this paper, we first introduce an adaptive
orthogonal integral image, which is an improved version of an orthogonal integral
image. After that, based on matching by tone mapping and the adaptive orthogonal
integral image, we propose a robust and accurate matching cost function that can
tolerate locally nonlinear intensity distortion. By using the adaptive orthogonal
integral image, the proposed matching cost function can adaptively construct
different support regions of arbitrary shapes and sizes for different pixels in
the reference image, so it can operate robustly within object boundaries.
Furthermore, we develop techniques to automatically estimate the values of the
parameters of our proposed function. We conduct experiments using the proposed
matching cost function and compare it with functions employing the census
transform, supporting local binary pattern, and adaptive normalized cross
correlation, as well as a mutual information-based matching cost function using
different stereo data sets. By using the adaptive orthogonal integral image, the
proposed matching cost function reduces the error from 21.51% to 15.73% in the
Middlebury data set, and from 15.9% to 10.85% in the Kitti data set, as compared
with using the orthogonal integral image. The experimental results indicate that
the proposed matching cost function is superior to the state-of-the-art matching
cost functions under radiometric variation.
PMID- 26415178
TI - Inpainting for Fringe Projection Profilometry Based on Geometrically Guided
Iterative Regularization.
AB - Conventional fringe projection profilometry methods often have difficulty in
reconstructing the 3D model of objects when the fringe images have the so-called
highlight regions due to strong illumination from nearby light sources. Within a
highlight region, the fringe pattern is often overwhelmed by the strong reflected
light. Thus, the 3D information of the object, which is originally embedded in
the fringe pattern, can no longer be retrieved. In this paper, a novel inpainting
algorithm is proposed to restore the fringe images in the presence of highlights.
The proposed method first detects the highlight regions based on a Gaussian
mixture model. Then, a geometric sketch of the missing fringes is made and used
as the initial guess of an iterative regularization procedure for regenerating
the missing fringes. The simulation and experimental results show that the
proposed algorithm can accurately reconstruct the 3D model of objects even when
their fringe images have large highlight regions. It significantly outperforms
the traditional approaches in both quantitative and qualitative evaluations.
PMID- 26415179
TI - Distributed Signal Decorrelation and Detection in Multi View Camera Networks
Using the Vector Sparse Matrix Transform.
AB - This paper introduces the vector sparse matrix transform (vector SMT), a new
decorrelating transform suitable for performing distributed processing of high
dimensional signals in sensor networks. We assume that each sensor in the network
encodes its measurements into vector outputs instead of scalar ones. The proposed
transform decorrelates a sequence of pairs of vector outputs, until these vectors
are decorrelated. In our experiments, we simulate distributed anomaly detection
by a network of cameras, monitoring a spatial region. Each camera records an
image of the monitored environment from its particular viewpoint and outputs a
vector encoding the image. Our results, with both artificial and real data, show
that the proposed vector SMT transform effectively decorrelates image
measurements from the multiple cameras in the network while maintaining low
overall communication energy consumption. Since it enables joint processing of
the multiple vector outputs, our method provides significant improvements to
anomaly detection accuracy when compared with the baseline case when the images
are processed independently.
PMID- 26415180
TI - Design and Error Analysis of a Vehicular AR System with Auto-Harmonization.
AB - This paper describes the design, development and testing of an AR system that was
developed for aerospace and ground vehicles to meet stringent accuracy and
robustness requirements. The system uses an optical see-through HMD, and thus
requires extremely low latency, high tracking accuracy and precision alignment
and calibration of all subsystems in order to avoid mis-registration and "swim".
The paper focuses on the optical/inertial hybrid tracking system and describes
novel solutions to the challenges with the optics, algorithms, synchronization,
and alignment with the vehicle and HMD systems. Tracker accuracy is presented
with simulation results to predict the registration accuracy. A car test is used
to create a through-the-eyepiece video demonstrating well-registered
augmentations of the road and nearby structures while driving. Finally, a
detailed covariance analysis of AR registration error is derived.
PMID- 26415181
TI - An Intelligent Decision System for Intraoperative Somatosensory Evoked Potential
Monitoring.
AB - Somatosensory evoked potential (SEP) is a useful, noninvasive technique widely
used for spinal cord monitoring during surgery. One of the main indicators of a
spinal cord injury is the drop in amplitude of the SEP signal in comparison to
the nominal baseline that is assumed to be constant during the surgery. However,
in practice, the real-time baseline is not constant and may vary during the
operation due to nonsurgical factors, such as blood pressure, anaesthesia, etc.
Thus, a false warning is often generated if the nominal baseline is used for SEP
monitoring. In current practice, human experts must be used to prevent this false
warning. However, these well-trained human experts are expensive and may not be
reliable and consistent due to various reasons like fatigue and emotion. In this
paper, an intelligent decision system is proposed to improve SEP monitoring.
First, the least squares support vector regression and multi-support vector
regression models are trained to construct the dynamic baseline from historical
data. Then a control chart is applied to detect abnormalities during surgery. The
effectiveness of the intelligent decision system is evaluated by comparing its
performance against the nominal baseline model by using the real experimental
datasets derived from clinical conditions.
PMID- 26415182
TI - Minimizing Stimulus Current in a Wearable Pudendal Nerve Stimulator Using
Computational Models.
AB - After spinal cord injury, functions of the lower urinary tract may be disrupted.
A wearable device with surface electrodes which can effectively control the
bladder functions would be highly beneficial to the patients. A trans-rectal
pudendal nerve stimulator may provide such a solution. However, the major
limiting factor in such a stimulator is the high level of current it requires to
recruit the nerve fibers. Also, the variability of the trajectory of the nerve in
different individuals should be considered. Using computational models and an
approximate trajectory of the nerve derived from an MRI study, it is demonstrated
in this paper that it may be possible to considerably reduce the required current
levels for trans-rectal stimulation of the pudendal nerve compared to the values
previously reported in the literature. This was corroborated by considering an
ensemble of possible and probable variations of the trajectory. The outcome of
this study suggests that trans-rectal stimulation of the pudendal nerve is a
plausible long term solution for treating lower urinary tract dysfunctions after
spinal cord injury.
PMID- 26415183
TI - Prediction of Protein Coding Regions Using a Wide-Range Wavelet Window Method.
AB - Prediction of protein coding regions is an important topic in the field of
genomic sequence analysis. Several spectrum-based techniques for the prediction
of protein coding regions have been proposed. However, the outstanding issue in
most of the proposed techniques is that these techniques depend on an
experimentally-selected, predefined value of the window length. In this paper, we
propose a new Wide-Range Wavelet Window (WRWW) method for the prediction of
protein coding regions. The analysis of the proposed wavelet window shows that
its frequency response can adapt its width to accommodate the change in the
window length so that it can allow or prevent frequencies other than the basic
frequency in the analysis of DNA sequences. This feature makes the proposed
window capable of analyzing DNA sequences with a wide range of the window lengths
without degradation in the performance. The experimental analysis of applying the
WRWW method and other spectrum-based methods to five benchmark datasets has shown
that the proposed method outperforms other methods along a wide range of the
window lengths. In addition, the experimental analysis has shown that the
proposed method is dominant in the prediction of both short and long exons.
PMID- 26415184
TI - Applying Monte Carlo Simulation to Biomedical Literature to Approximate Genetic
Network.
AB - Biologists often need to know the set of genes associated with a given set of
genes or a given disease. We propose in this paper a classifier system called
Monte Carlo for Genetic Network (MCforGN) that can construct genetic networks,
identify functionally related genes, and predict gene-disease associations.
MCforGN identifies functionally related genes based on their co-occurrences in
the abstracts of biomedical literature. For a given gene g , the system first
extracts the set of genes found within the abstracts of biomedical literature
associated with g. It then ranks these genes to determine the ones with high co
occurrences with g . It overcomes the limitations of current approaches that
employ analytical deterministic algorithms by applying Monte Carlo Simulation to
approximate genetic networks. It does so by conducting repeated random sampling
to obtain numerical results and to optimize these results. Moreover, it analyzes
results to obtain the probabilities of different genes' co-occurrences using
series of statistical tests. MCforGN can detect gene-disease associations by
employing a combination of centrality measures (to identify the central genes in
disease-specific genetic networks) and Monte Carlo Simulation. MCforGN aims at
enhancing state-of-the-art biological text mining by applying novel extraction
techniques. We evaluated MCforGN by comparing it experimentally with nine
approaches. Results showed marked improvement.
PMID- 26415185
TI - Estimating Sensorimotor Mapping From Stimuli to Behaviors to Infer C. elegans
Movements by Neural Transmission Ability Through Connectome Databases.
AB - One of the ultimate goals of computational neuroscience is to quantitatively
connect between complex neural circuits and behaviors. In the past decades, the
touch response circuit in Caenorhabditis elegans (C. elegans) has extensively
been investigated in studies using genetically modified or laser-ablated worms.
Synaptic connections, including chemical and electrical synapses, have been
identified for most neurons in the C. elegans. However, we still do not know
whether the empirically observed touch responses can be derived from connectome
reconstructed from databases. To address this issue, we defined the transmission
abilities (or levels) of neurons in a rate model in order to infer the behaviors
of wild-type and ablated worms in response to posterior/nose/anterior touch
stimuli. Our analysis showed that transmission abilities can be used to identify
sensorimotor mapping from stimuli to movements and then to infer the C. elegans
behaviors under simulations based on the perspective of decision-making, and
provide useful information about how chemical and electronic synapses should be
combined in the neural network movement analysis. This paper reveals an efficient
tool that provided insights into the functions of complex neural circuits.
PMID- 26415186
TI - Decomposition Techniques for Multilayer Perceptron Training.
AB - In this paper, we consider the learning problem of multilayer perceptrons (MLPs)
formulated as the problem of minimizing a smooth error function. As well known,
the learning problem of MLPs can be a difficult nonlinear nonconvex optimization
problem. Typical difficulties can be the presence of extensive flat regions and
steep sided valleys in the error surface, and the possible large number of
training data and of free network parameters. We define a wide class of batch
learning algorithms for MLP, based on the use of block decomposition techniques
in the minimization of the error function. The learning problem is decomposed
into a sequence of smaller and structured minimization problems in order to
advantageously exploit the structure of the objective function. Theoretical
convergence results are established, and a specific algorithm is constructed and
evaluated through an extensive numerical experimentation. The comparisons with
the state-of-the-art learning algorithms show the effectiveness of the proposed
techniques.
PMID- 26415187
TI - RBoost: Label Noise-Robust Boosting Algorithm Based on a Nonconvex Loss Function
and the Numerically Stable Base Learners.
AB - AdaBoost has attracted much attention in the machine learning community because
of its excellent performance in combining weak classifiers into strong
classifiers. However, AdaBoost tends to overfit to the noisy data in many
applications. Accordingly, improving the antinoise ability of AdaBoost plays an
important role in many applications. The sensitiveness to the noisy data of
AdaBoost stems from the exponential loss function, which puts unrestricted
penalties to the misclassified samples with very large margins. In this paper, we
propose two boosting algorithms, referred to as RBoost1 and RBoost2, which are
more robust to the noisy data compared with AdaBoost. RBoost1 and RBoost2
optimize a nonconvex loss function of the classification margin. Because the
penalties to the misclassified samples are restricted to an amount less than one,
RBoost1 and RBoost2 do not overfocus on the samples that are always misclassified
by the previous base learners. Besides the loss function, at each boosting
iteration, RBoost1 and RBoost2 use numerically stable ways to compute the base
learners. These two improvements contribute to the robustness of the proposed
algorithms to the noisy training and testing samples. Experimental results on the
synthetic Gaussian data set, the UCI data sets, and a real malware behavior data
set illustrate that the proposed RBoost1 and RBoost2 algorithms perform better
when the training data sets contain noisy data.
PMID- 26415188
TI - A New Continuous-Time Equality-Constrained Optimization to Avoid Singularity.
AB - In equality-constrained optimization, a standard regularity assumption is often
associated with feasible point methods, namely, that the gradients of constraints
are linearly independent. In practice, the regularity assumption may be violated.
In order to avoid such a singularity, a new projection matrix is proposed based
on which a feasible point method to continuous-time, equality-constrained
optimization is developed. First, the equality constraint is transformed into a
continuous-time dynamical system with solutions that always satisfy the equality
constraint. Second, a new projection matrix without singularity is proposed to
realize the transformation. An update (or say a controller) is subsequently
designed to decrease the objective function along the solutions of the
transformed continuous-time dynamical system. The invariance principle is then
applied to analyze the behavior of the solution. Furthermore, the proposed method
is modified to address cases in which solutions do not satisfy the equality
constraint. Finally, the proposed optimization approach is applied to three
examples to demonstrate its effectiveness.
PMID- 26415189
TI - Sparse Bayesian Classification of EEG for Brain-Computer Interface.
AB - Regularization has been one of the most popular approaches to prevent overfitting
in electroencephalogram (EEG) classification of brain-computer interfaces (BCIs).
The effectiveness of regularization is often highly dependent on the selection of
regularization parameters that are typically determined by cross-validation (CV).
However, the CV imposes two main limitations on BCIs: 1) a large amount of
training data is required from the user and 2) it takes a relatively long time to
calibrate the classifier. These limitations substantially deteriorate the
system's practicability and may cause a user to be reluctant to use BCIs. In this
paper, we introduce a sparse Bayesian method by exploiting Laplace priors,
namely, SBLaplace, for EEG classification. A sparse discriminant vector is
learned with a Laplace prior in a hierarchical fashion under a Bayesian evidence
framework. All required model parameters are automatically estimated from
training data without the need of CV. Extensive comparisons are carried out
between the SBLaplace algorithm and several other competing methods based on two
EEG data sets. The experimental results demonstrate that the SBLaplace algorithm
achieves better overall performance than the competing algorithms for EEG
classification.
PMID- 26415190
TI - Efficient $?chi ^{2}$ Kernel Linearization via Random Feature Maps.
AB - Explicit feature mapping is an appealing way to linearize additive kernels, such
as chi2 kernel for training large-scale support vector machines (SVMs). Although
accurate in approximation, feature mapping could pose computational challenges in
high-dimensional settings as it expands the original features to a higher
dimensional space. To handle this issue in the context of chi2 kernel SVMs
learning, we introduce a simple yet efficient method to approximately linearize
chi2 kernel through random feature maps. The main idea is to use sparse random
projection to reduce the dimensionality of feature maps while preserving their
approximation capability to the original kernel. We provide approximation error
bound for the proposed method. Furthermore, we extend our method to chi2 multiple
kernel SVMs learning. Extensive experiments on large-scale image classification
tasks confirm that the proposed approach is able to significantly speed up the
training process of the chi2 kernel SVMs at almost no cost of testing accuracy.
PMID- 26415191
TI - A Comparison of Algorithms for Learning Hidden Variables in Bayesian Factor
Graphs in Reduced Normal Form.
AB - Bayesian-directed acyclic discrete-variable graphs are reduced to a simplified
normal form made up of only replicator units (or equal constraint units), source,
and single-input/single-output blocks. In this framework, the same adaptation
algorithm can be applied to all the parametric blocks. We obtain and compare
adaptation rules derived from a constrained maximum likelihood formulation and a
minimum Kullback-Leibler divergence criterion using Karush-Kuhn-Tucker
conditions. The learning algorithms are compared with two other updating
equations based on localized decisions and on a variational approximation,
respectively. The performance of the various algorithms is verified on synthetic
data sets for various architectures. Factor graphs in reduced normal form provide
an appealing framework for rapid deployment of Bayesian-directed graphs in the
applications.
PMID- 26415192
TI - Supraventricular Tachycardia Classification in the 12-Lead ECG Using Atrial Waves
Detection and a Clinically Based Tree Scheme.
AB - Specific supraventricular tachycardia (SVT) classification using surface ECG is
considered a challenging task, since the atrial electrical activity (AEA) waves,
which are a crucial element for obtaining diagnosis, are frequently hidden. In
this paper, we present a fully automated SVT classification method that embeds
our recently developed hidden AEA detector in a clinically based tree scheme. The
process begins with initial noise removal and QRS detection. Then, ventricular
features are extracted. According to these features, an initial AEA-wave search
window is defined and a single AEA-wave is detected. Using a synthetic Gaussian
signal and a linear combination of 12-lead ECG signals, all AEA-waves are
detected. In accord with the atrial and ventricular information found,
classification to atrial fibrillation, atrial flutter, atrioventricular nodal
reentry tachycardia, atrioventricular reentry tachycardia, or sinus rhythm is
performed in the framework of a clinically oriented decision tree. A study was
performed to evaluate the classification from 68 patients (26 were used for the
classifier's design, 42 were used for its validation). Average sensitivity of
83.21% [95% confidence interval (CI): 79.33-86.49%], average specificity of
95.80% (95% CI: 94.73-96.67%), and average accuracy of 93.29% (95% CI: 92.13
94.28%) were achieved compared to the definite diagnosis. In conclusion, the
presented method may serve as a valuable decision support tool, allowing accurate
detection of SVTs using noninvasive means.
PMID- 26415193
TI - MISTICA: Minimum Spanning Tree-Based Coarse Image Alignment for Microscopy Image
Sequences.
AB - Registration of an in vivo microscopy image sequence is necessary in many
significant studies, including studies of atherosclerosis in large arteries and
the heart. Significant cardiac and respiratory motion of the living subject,
occasional spells of focal plane changes, drift in the field of view, and long
image sequences are the principal roadblocks. The first step in such a
registration process is the removal of translational and rotational motion. Next,
a deformable registration can be performed. The focus of our study here is to
remove the translation and/or rigid body motion that we refer to here as coarse
alignment. The existing techniques for coarse alignment are unable to accommodate
long sequences often consisting of periods of poor quality images (as quantified
by a suitable perceptual measure). Many existing methods require the user to
select an anchor image to which other images are registered. We propose a novel
method for coarse image sequence alignment based on minimum weighted spanning
trees (MISTICA) that overcomes these difficulties. The principal idea behind
MISTICA is to reorder the images in shorter sequences, to demote nonconforming or
poor quality images in the registration process, and to mitigate the error
propagation. The anchor image is selected automatically making MISTICA completely
automated. MISTICA is computationally efficient. It has a single tuning parameter
that determines graph width, which can also be eliminated by the way of
additional computation. MISTICA outperforms existing alignment methods when
applied to microscopy image sequences of mouse arteries.
PMID- 26415195
TI - Security Games With Unknown Adversarial Strategies.
AB - The security community has witnessed a significant increase in the number of
different types of security threats. This situation calls for the design of new
techniques that can be incorporated into security protocols to meet these
challenges successfully. An important tool for developing new security protocols
as well as estimating their effectiveness is game theory. This game theory
framework usually involves two players or agents: 1) a protector and 2) an
adversary, and two patterns of agent behavior are considered: 1) selfish
behavior, where each of the agents wants to maximize his payoff; and 2) leader
and follower behavior, where one agent (the leader) expects that the other agent
(the follower) will respond to the leader's strategy. Such an approach assumes
that the agents agree on which strategy to apply in advance. In this paper, this
strong assumption is relaxed. Namely, the following question is considered: what
happens if it is unknown a priori what pattern of behavior the adversary is going
to use, or in other words, it is not known, what game he intends to play? Using a
simple game-theoretic model, it is shown that the protector can lose if he does
not take into account the possibility that the adversary can play a game other
than the one the protector has in mind. Further considered is a repeated game in
which the protector can learn about the presence of an adversary, and the
behavior of belief probabilities is analyzed in this setting.
PMID- 26415194
TI - Estimation of Respiratory Rates Using the Built-in Microphone of a Smartphone or
Headset.
AB - This paper proposes accurate respiratory rate estimation using nasal breath sound
recordings from a smartphone. Specifically, the proposed method detects nasal
airflow using a built-in smartphone microphone or a headset microphone placed
underneath the nose. In addition, we also examined if tracheal breath sounds
recorded by the built-in microphone of a smartphone placed on the paralaryngeal
space can also be used to estimate different respiratory rates ranging from as
low as 6 breaths/min to as high as 90 breaths/min. The true breathing rates were
measured using inductance plethysmography bands placed around the chest and the
abdomen of the subject. Inspiration and expiration were detected by averaging the
power of nasal breath sounds. We investigated the suitability of using the
smartphone-acquired breath sounds for respiratory rate estimation using two
different spectral analyses of the sound envelope signals: The Welch periodogram
and the autoregressive spectrum. To evaluate the performance of the proposed
methods, data were collected from ten healthy subjects. For the breathing range
studied (6-90 breaths/min), experimental results showed that our approach
achieves an excellent performance accuracy for the nasal sound as the median
errors were less than 1% for all breathing ranges. The tracheal sound, however,
resulted in poor estimates of the respiratory rates using either spectral method.
For both nasal and tracheal sounds, significant estimation outliers resulted for
high breathing rates when subjects had nasal congestion, which often resulted in
the doubling of the respiratory rates. Finally, we show that respiratory rates
from the nasal sound can be accurately estimated even if a smartphone's
microphone is as far as 30 cm away from the nose.
PMID- 26415196
TI - Saturated Nussbaum Function Based Approach for Robotic Systems With Unknown
Actuator Dynamics.
AB - This paper presents a saturated Nussbaum function based approach for robotic
systems with unknown actuator dynamics. To eliminate the effect of the control
shock from the traditional Nussbaum function, a new type of the saturated
Nussbaum function is developed with the idea of time-elongation. Moreover, by
exploiting properties of the proposed Nussbaum function, a promising theorem is
established to deal with unknown multiple actuator nonlinearities. In what
follows, the proposed theorem is integrated with the adaptive control technique
such that the stability analysis of the robotic system is completed. It thus
guarantees that the state of the robotic system asymptotically converges to the
desired trajectory. Finally, comparative studies are carried out to validate the
effectiveness and the superiority of the proposed approach.
PMID- 26415197
TI - Adaptive Task-Space Cooperative Tracking Control of Networked Robotic
Manipulators Without Task-Space Velocity Measurements.
AB - In this paper, the task-space cooperative tracking control problem of networked
robotic manipulators without task-space velocity measurements is addressed. To
overcome the problem without task-space velocity measurements, a novel task-space
position observer is designed to update the estimated task-space position and to
simultaneously provide the estimated task-space velocity, based on which an
adaptive cooperative tracking controller without task-space velocity measurements
is presented by introducing new estimated task-space reference velocity and
acceleration. Furthermore, adaptive laws are provided to cope with uncertain
kinematics and dynamics and rigorous stability analysis is given to show
asymptotical convergence of the task-space tracking and synchronization errors in
the presence of communication delays under strongly connected directed graphs.
Simulation results are given to demonstrate the performance of the proposed
approach.
PMID- 26415198
TI - Causality Analysis of fMRI Data Based on the Directed Information Theory
Framework.
AB - This paper aims to conduct fMRI-based causality analysis in brain connectivity by
exploiting the directed information (DI) theory framework. Unlike the well-known
Granger causality (GC) analysis, which relies on the linear prediction technique,
the DI theory framework does not have any modeling constraints on the sequences
to be evaluated and ensures estimation convergence. Moreover, it can be used to
generate the GC graphs. In this paper, first, we introduce the core concepts in
the DI framework. Second, we present how to conduct causality analysis using DI
measures between two time series. We provide the detailed procedure on how to
calculate the DI for two finite-time series. The two major steps involved here
are optimal bin size selection for data digitization and probability estimation.
Finally, we demonstrate the applicability of DI-based causality analysis using
both the simulated data and experimental fMRI data, and compare the results with
that of the GC analysis. Our analysis indicates that GC analysis is effective in
detecting linear or nearly linear causal relationship, but may have difficulty in
capturing nonlinear causal relationships. On the other hand, DI-based causality
analysis is more effective in capturing both linear and nonlinear causal
relationships. Moreover, it is observed that brain connectivity among different
regions generally involves dynamic two-way information transmissions between
them. Our results show that when bidirectional information flow is present, DI is
more effective than GC to quantify the overall causal relationship.
PMID- 26415199
TI - Noncontact Monitoring of Blood Oxygen Saturation Using Camera and Dual-Wavelength
Imaging System.
AB - We present a noncontact method to monitor blood oxygen saturation (SpO2). The
method uses a CMOS camera with a trigger control to allow recording of
photoplethysmography (PPG) signals alternatively at two particular wavelengths,
and determines the SpO2 from the measured ratios of the pulsatile to the
nonpulsatile components of the PPG signals at these wavelengths. The signal-to
noise ratio (SNR) of the SpO2 value depends on the choice of the wavelengths. We
found that the combination of orange (lambda = 611 nm) and near infrared (lambda
= 880 nm) provides the best SNR for the noncontact video-based detection method.
This combination is different from that used in traditional contact-based SpO 2
measurement since the PPG signal strengths and camera quantum efficiencies at
these wavelengths are more amenable to SpO2 measurement using a noncontact
method. We also conducted a small pilot study to validate the noncontact method
over an SpO2 range of 83%-98%. This study results are consistent with those
measured using a reference contact SpO2 device ( r = 0.936, ). The presented
method is particularly suitable for tracking one's health and wellness at home
under free-living conditions, and for those who cannot use traditional contact
based PPG devices.
PMID- 26415200
TI - 3-D Lung Segmentation by Incremental Constrained Nonnegative Matrix
Factorization.
AB - Accurate lung segmentation from large-size 3-D chest-computed tomography images
is crucial for computer-assisted cancer diagnostics. To efficiently segment a 3-D
lung, we extract voxel-wise features of spatial image contexts by unsupervised
learning with a proposed incremental constrained nonnegative matrix factorization
(ICNMF). The method applies smoothness constraints to learn the features, which
are more robust to lung tissue inhomogeneities, and thus, help to better segment
internal lung pathologies than the known state-of-the-art techniques. Compared to
the latter, the ICNMF depends less on the domain expert knowledge and is more
easily tuned due to only a few control parameters. Also, the proposed slice-wise
incremental learning with due regard for interslice signal dependencies decreases
the computational complexity of the NMF-based segmentation and is scalable to
very large 3-D lung images. The method is quantitatively validated on simulated
realistic lung phantoms that mimic different lung pathologies (seven datasets),
in vivo datasets for 17 subjects, and 55 datasets from the Lobe and Lung Analysis
2011 (LOLA11) study. For the in vivo data, the accuracy of our segmentation
w.r.t. the ground truth is 0.96 by the Dice similarity coefficient, 9.0 mm by the
modified Hausdorff distance, and 0.87% by the absolute lung volume difference,
which is significantly better than for the NMF-based segmentation. In spite of
not being designed for lungs with severe pathologies and of no agreement between
radiologists on the ground truth in such cases, the ICNMF with its total accuracy
of 0.965 was ranked fifth among all others in the LOLA11. After excluding the
nine too pathological cases from the LOLA11 dataset, the ICNMF accuracy increased
to 0.986.
PMID- 26415201
TI - Confidence Estimation for Medical Image Registration Based On Stereo Confidences.
AB - In this paper, we propose a novel method to estimate the confidence of a
registration that does not require any ground truth, is independent from the
registration algorithm and the resulting confidence is correlated with the amount
of registration error. We first apply a local search to match patterns between
the registered image pairs. Local search induces a cost space per voxel which we
explore further to estimate the confidence of the registration similar to
confidence estimation algorithms for stereo matching. We test our method on both
synthetically generated registration errors and on real registrations with ground
truth. The experimental results show that our confidence measure can estimate
registration errors and it is correlated with local errors.
PMID- 26415202
TI - Encoding color information for visual tracking: Algorithms and benchmark.
AB - While color information is known to provide rich discriminative clues for visual
inference, most modern visual trackers limit themselves to the grayscale realm.
Despite recent efforts to integrate color in tracking, there is a lack of
comprehensive understanding of the role color information can play. In this
paper, we attack this problem by conducting a systematic study from both the
algorithm and benchmark perspectives. On the algorithm side, we comprehensively
encode 10 chromatic models into 16 carefully selected state-of-the-art visual
trackers. On the benchmark side, we compile a large set of 128 color sequences
with ground truth and challenge factor annotations (e.g., occlusion). A thorough
evaluation is conducted by running all the color-encoded trackers, together with
two recently proposed color trackers. A further validation is conducted on an
RGBD tracking benchmark. The results clearly show the benefit of encoding color
information for tracking. We also perform detailed analysis on several issues,
including the behavior of various combinations between color model and visual
tracker, the degree of difficulty of each sequence for tracking, and how
different challenge factors affect the tracking performance. We expect the study
to provide the guidance, motivation, and benchmark for future work on encoding
color in visual tracking.
PMID- 26415203
TI - Position-Independent Decoding of Movement Intention for Proportional Myoelectric
Interfaces.
AB - In this decade, myoelectric interfaces based on pattern recognition have gained
considerable attention thanks to their naturalness enabling human intentions to
be conveyed to and in control of a machine. However, the high variations of
electromyogram signal patterns caused by arm position changes prohibit
application to the real world. In this paper, we propose a novel method of
decoding movement intentions robust to arm position changes towards proportional
myoelectric interfaces. Specifically, we devise the position-independent decoding
that estimates the likelihood of different arm positions, which we predefine
during a training step, and also decodes the movement intention in a unified
framework. The proposed method has an advantage that could be used to decode the
movement intentions on untrained arm positions in a realistic scenario. Our
experimental results showed that the proposed method could successfully decode
the continuous movement intentions (e.g., flexion/extension and radial/ulnar
deviation) on both trained and untrained arm positions. Our study also proved the
effectiveness of the proposed method by comparing the existing methods in terms
of the decoded trajectories as movement intentions in untrained arm positions.
PMID- 26415204
TI - Bovine Osteochondral Tissues: A Questionable Model to Evaluate Mechanical Loading
In Vitro.
AB - Articular cartilage exists within synovial joints to adsorb and distribute
mechanical loads to the subchondral bone. Mechanical loading is one aspect of a
wide range of microenvironmental stressors that contribute to the maintenance of
articular cartilage. The aim of the current study was to characterize bovine
osteochondral tissues and to assess their suitability to serve as a model for
investigating the effects of mechanical loading on cartilage tissue in vitro
using a custom-made reactor system. Osteochondral tissues were harvested from
bovine knee joints and cultured up to 24 days in loaded and unloaded conditions.
Notably, we found a considerable zone-specific heterogeneity between cartilage
explants harvested from the same joint as evidenced by histology and gene
expression levels. Results using the reactor system revealed that differences
observed after mechanical loading varied within the range of the heterogeneity
observed amongst the different cartilage explants. Thus, it may be difficult to
obtain reliable and reproducible data in mechanical loading experiments from
these tissues in vitro, especially in cases where small variations between the
experimental groups are expected. This will likely lead to the reporting of false
positives or negatives in studies investigating the effect of mechanical load on
the function of cartilage tissue.
PMID- 26415205
TI - Flexible Bioimpedance Sensor for Label-Free Detection of Cell Viability and
Biomass.
AB - We introduce a flexible microfluidic bioimpedance sensor that is capable of
detecting biomass and cell viability variations in a cell suspension. The sensor
is developed on indium tin oxide (ITO) coated polyethylene terephthalate (PET)
substrate and is devoid of gold, silicon, PDMS, or glass. In conjugation with a
custom built PCB read-out module, the impedance characteristics of a cell
suspension can be measured within one minute of sample introduction using liquid
volumes less than 5 MUL. The portable sensor system occupies very little bench
space and has the potential to be developed as a disposable electrical
bioimpedance probe for rapid detection of dielectric variations in a biological
suspension. The sensor is designed to generate a differential impedance spectra
exclusive to a cell suspension with a dual-electrode-pair system. The potential
of the sensor to discriminate between live and heat treated Saccharomyces
cerevisiae is demonstrated in this study. The disposable sensor along with the
distance variation technique is touted to be an inexpensive alternative to some
of the existing online disposable biomass detection probes and electrochemical
sensors.
PMID- 26415206
TI - A Microflow Cytometer Based on a Disposable Microfluidic Chip With Side Scatter
and Fluorescence Detection Capability.
AB - In this paper, we present a microflow cytometer based on a polydimethylsiloxane
(PDMS) microfluidic chip. The PDMS chip has a smooth sidewall because of the
proposed double molding process. Thus, the side scatter (SSC) detection can be
used for the cytometer. The coincidence error using the sheathless focus
mechanism is less than 0.069%. Using Flow-Check alignment beads for the counting
experiment, the coefficient of variation (CV) of the SSC and the fluorescein
isothiocyanate (FITC) channel can reach 8.37% and 2.46%, respectively. The gating
of the lymphocytes according to CD45/SSC was also demonstrated successfully. It
proves that the chip is a promising solution for point of care (POC) microflow
cytometers.
PMID- 26415207
TI - Towards an Endpoint Cell Motility Assay by a Microfluidic Platform.
AB - In vitro cell motility assays are frequently used in the study of cell migration
in response to anti-cancer drug treatment. Microfluidic systems represent a
unique tool for the in vitro analysis of cell motility. However, they usually
rely on using time-lapse microscopy to record the spatial temporal locations of
the individual cells being tested. This has created a bottleneck for microfluidic
systems to perform high-throughput experiments due to requirement of a costly
time-lapse microscopy system. Here, we describe the development of a portable
microfluidic device for endpoint analysis of cell motility. The reported device
incorporates a cell alignment feature to position the seeded cells on the same
initial location, so that the cells' motilities can be analyzed based on their
locations at the end of the experiment after the cells have migrated. We show
that the device was able to assess cancer cell motility after treatment with a
migration inhibitory drug Indole-3-carbinol on MDA-MB-231 breast cancer cells,
demonstrating the applicability of our device in screening anti-cancer drug
compounds on cancer cells.
PMID- 26415208
TI - Predicting Hub Genes Associated with Cervical Cancer through Gene Co-Expression
Networks.
AB - Cervical cancer is the third most common malignancy in women worldwide. It
remains a leading cause of cancer-related death for women in developing
countries. In order to contribute to the treatment of the cervical cancer, in our
work, we try to find a few key genes resulting in the cervical cancer. Employing
functions of several bioinformatics tools, we selected 143 differentially
expressed genes (DEGs) associated with the cervical cancer. The results of
bioinformatics analysis show that these DEGs play important roles in the
development of cervical cancer. Through comparing two differential co-expression
networks (DCNs) at two different states, we found a common sub-network and two
differential sub-networks as well as some hub genes in three sub-networks.
Moreover, some of the hub genes have been reported to be related to the cervical
cancer. Those hub genes were analyzed from Gene Ontology function enrichment,
pathway enrichment and protein binding three aspects. The results can help us
understand the development of the cervical cancer and guide further experiments
about the cervical cancer.
PMID- 26415209
TI - IAS: Interaction Specific GO Term Associations for Predicting Protein-Protein
Interaction Networks.
AB - Proteins carry out their function in a cell through interactions with other
proteins. A large scale protein-protein interaction (PPI) network of an organism
provides static yet an essential structure of interactions, which is valuable
clue for understanding the functions of proteins and pathways. PPIs are
determined primarily by experimental methods; however, computational PPI
prediction methods can supplement or verify PPIs identified by experiment. Here,
we developed a novel scoring method for predicting PPIs from Gene Ontology (GO)
annotations of proteins. Unlike existing methods that consider functional
similarity as an indication of interaction between proteins, the new score, named
the protein-protein Interaction Association Score (IAS), was computed from GO
term associations of known interacting protein pairs in 49 organisms. IAS was
evaluated on PPI data of six organisms and found to outperform existing GO term
based scoring methods. Moreover, consensus scoring methods that combine different
scores further improved performance of PPI prediction.
PMID- 26415210
TI - Nucleosome Positioning of Intronless Genes in the Human Genome.
AB - Nucleosomes, the basic units of chromatin, are involved in transcription
regulation and DNA replication. Intronless genes, which constitute 3 percent of
the human genome, differ from intron-containing genes in evolution and function.
Our analysis reveals that nucleosome positioning shows a distinct pattern in
intronless and intron-containing genes. The nucleosome occupancy upstream of
transcription start sites of intronless genes is lower than that of intron
containing genes. In contrast, high occupancy and well positioned nucleosomes are
observed along the gene body of intronless genes, which is perfectly consistent
with the barrier nucleosome model. Intronless genes have a significantly lower
expression level than intron-containing genes and most of them are not expressed
in CD4+ T cell lines and GM12878 cell lines, which results from their tissue
specificity. However, the highly expressed genes are at the same expression level
between the two types of genes. The highly expressed intronless genes require a
higher density of RNA Pol II in an elongating state to compensate for the lack of
introns. Additionally, 5' and 3' nucleosome depleted regions of highly expressed
intronless genes are deeper than those of highly expressed intron-containing
genes.
PMID- 26415211
TI - [Cell phone vs paracetamol].
PMID- 26415212
TI - [Pediatrics activity in military theatre].
PMID- 26415213
TI - [Parasitic intestinal infections are still frequent].
PMID- 26415214
TI - [Some reflections on the classification of African obstetric fistulas].
AB - While the English-speaking world may have reached a consensus about Kees
Waaldjik's classification of obstetric fistulas, no unanimity around this
classification exists among French-speaking medical workers. The objective of
this review is to propose a classification, based on long experience in the care
of these women, by setting up a comparison with Waaldjik's. Our classification
takes two criteria into account: (1) the environment of the fistula, that is: (a)
fistula with a soft (relatively unscarred) vagina, b) fistula with vaginal
sclerosis (bands or adhesions, vaginal stenosis or atresia), (c) vesicovaginal
fistula associated with a (high or low) rectovaginal fistula or perineal
lacerations (first, second or third degree); (2) the anatomical site of fistula,
of which there are five types: (a) type I: fistula of the vesicovaginal wall, (b)
type II: vesico-cervico-urethral fistula, with two major subgroups: type IIA
(without destruction of the urethra) and type IIB (with destruction of the
urethra), type IIA being subdivided in three subgroups: IIAa, IIAB and cIAI, (c)
type III fistulae trigono-Neck utero-vaginal, (d) type IV: complex mixed fistula,
(e) type V, high fistulas: the vesico-cervical-uterine fistula and classical
vesicouterine. CONCLUSION: Our classification is simple, not simplistic, with
some resemblance to that of Waaldjjik.
PMID- 26415215
TI - Fluid mechanics aspects of magnetic drug targeting.
AB - Experiments and numerical simulations using a flow phantom for magnetic drug
targeting have been undertaken. The flow phantom is a half y-branched tube
configuration where the main tube represents an artery from which a tumour
supplying artery, which is simulated by the side branch of the flow phantom,
branches off. In the experiments a quantification of the amount of magnetic
particles targeted towards the branch by a magnetic field applied via a permanent
magnet is achieved by impedance measurement using sensor coils. Measuring the
targeting efficiency, i.e. the relative amount of particles targeted to the side
branch, for different field configurations one obtains targeting maps which
combine the targeting efficiency with the magnetic force densities in
characteristic points in the flow phantom. It could be shown that targeting
efficiency depends strongly on the magnetic field configuration. A corresponding
numerical model has been set up, which allows the simulation of targeting
efficiency for variable field configuration. With this simulation good agreement
of targeting efficiency with experimental data has been found. Thus, the basis
has been laid for future calculations of optimal field configurations in clinical
applications of magnetic drug targeting. Moreover, the numerical model allows the
variation of additional parameters of the drug targeting process and thus an
estimation of the influence, e.g. of the fluid properties on the targeting
efficiency. Corresponding calculations have shown that the non-Newtonian
behaviour of the fluid will significantly influence the targeting process, an
aspect which has to be taken into account, especially recalling the fact that the
viscosity of magnetic suspensions depends strongly on the magnetic field strength
and the mechanical load.
PMID- 26415216
TI - RIOK3 keeps MDA5 inactive.
PMID- 26415217
TI - Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA
damage response.
AB - The MUS81 protein belongs to a conserved family of DNA structure-specific
nucleases that play important roles in DNA replication and repair. Inactivation
of the Mus81 gene in mice has no major deleterious consequences for embryonic
development, although cancer susceptibility has been reported. We have
investigated the role of MUS81 in human cells by acutely depleting the protein
using shRNAs. We found that MUS81 depletion from human fibroblasts leads to
accumulation of ssDNA and a constitutive DNA damage response that ultimately
activates cellular senescence. Moreover, we show that MUS81 is required for
efficient replication fork progression during an unperturbed S-phase, and for
recovery of productive replication following replication stalling. These results
demonstrate essential roles for the MUS81 nuclease in maintenance of replication
fork integrity.
PMID- 26415218
TI - S-nitrosylation and MSC-mediated body composition.
PMID- 26415219
TI - Targeted cancer therapy with ribosome biogenesis inhibitors: a real possibility?
AB - The effects of many chemotherapeutic drugs on ribosome biogenesis have been
underestimated for a long time. Indeed, many drugs currently used for cancer
treatment--and which are known to either damage DNA or hinder DNA synthesis--have
been shown to exert their toxic action mainly by inhibiting rRNA synthesis or
maturation. Moreover, there are new drugs that have been proposed recently for
cancer chemotherapy, which only hinder ribosome biogenesis without any genotoxic
activity. Even though ribosome biogenesis occurs in both normal and cancer cells,
whether resting or proliferating, there is evidence that the selective inhibition
of ribosome biogenesis may, in some instances, result in a selective damage to
neoplastic cells. The higher sensitivity of cancer cells to inhibitors of rRNA
synthesis appears to be the consequence of either the loss of the mechanisms
controlling the cell cycle progression or the acquisition of activating oncogene
and inactivating tumor suppressor gene mutations that up-regulate the ribosome
biogenesis rate. This article reviews those cancer cell characteristics on which
the selective cancer cell cytotoxicity induced by the inhibitors of ribosome
biogenesis is based.
PMID- 26415221
TI - Wnt activated beta-catenin and YAP proteins enhance the expression of non-coding
RNA component of RNase MRP in colon cancer cells.
AB - RMRP, the RNA component of mitochondrial RNA processing endoribonuclease, is a
non-coding RNA (ncRNA) part of the RNase MRP complex functioning in mitochondrial
and ribosomal RNA processing. Even though various mutations in the RMRP gene are
linked to developmental defects and pathogenesis, its relevance to cancer
etiology has not been well established. Here we examined the expression of RMRP
and found a significant increase in colorectal and breast cancer patient tissues.
So we tested whether the oncogenic signaling pathways, Wnt/beta-catenin and
Hippo/YAP pathways, are relevant to the enhanced expression of RMRP in cancer
cells because of the predicted beta-catenin/TCF and YAP/TBX5 elements in the
upstream regions of the RMRP gene. As expected, Wnt signal activation
significantly induced the RMRP transcription thru beta-catenin and YAP
transcription factors. More importantly, YAP protein was critical for RMRP
transcription by association to the proximal site near the transcription start
site of the RMRP gene, a Pol III promoter, along with beta-catenin and TBX5
proteins. We propose that the interplay of Wnt and Hippo signaling pathways could
regulate target genes, coding or non-coding, by the beta-catenin/YAP/TBX5
transcription complex in cancer cells.
PMID- 26415223
TI - Prognostic score models for survival of nasopharyngeal carcinoma patients treated
with intensity-modulated radiotherapy and chemotherapy.
AB - PURPOSE: To establish accurate prognostic score models to predict survival for
patients with nasopharyngeal carcinoma (NPC), treated with intensity-modulated
radiotherapy (IMRT) and chemotherapy. MATERIALS AND METHODS: Six hundred and
seventy-five patients with newly diagnosed, nonmetastatic and histologically
proven NPC who were treated with IMRT and chemotherapy were analyzed
retrospectively. Samples were split randomly into a training set (n = 338) and a
test set (n = 337) to analyze. All data from the training set were used to
perform an extensive survival analysis and to develop multivariate nomograms
based on Cox regression. Data from the test set was used as an external
validation set. Risk group stratification was proposed for the nomograms.
RESULTS: The nomograms are able to predict survival with a C-index for external
validation of local recurrence-free survival (LRFS; 0.66, 95% CI: 0.58-0.74),
distant metastasis-free survival (DMFS; 0.73, 95% CI: 0.66-0.79), and disease
specific survival (DSS; 0.73, 95% CI: 0.67-0.79). The calibration curve for
probability of survival showed good agreement between prediction by nomogram and
actual observation. The C-index of the nomogram for LRFS, DMFS and DSS were
statistically higher than the C-index values of the AJCC seventh edition (P <
0.001). In the test set, the nomogram discrimination was also superior to the
AJCC Staging systems (P < 0.001). The stratification in risk groups allows
significant distinction between Kaplan-Meier curves for outcome. CONCLUSIONS:
Prognostic score models were successfully established and validated to predict
LRFS, DMFS, and DSS over a 5-year period after IMRT and chemotherapy, which will
be useful for individual treatment.
PMID- 26415222
TI - Copper activates HIF-1alpha/GPER/VEGF signalling in cancer cells.
AB - Copper promotes tumor angiogenesis, nevertheless the mechanisms involved remain
to be fully understood. We have recently demonstrated that the G-protein estrogen
receptor (GPER) cooperates with hypoxia inducible factor-1alpha (HIF-1alpha)
toward the regulation of the pro-angiogenic factor VEGF. Here, we show that
copper sulfate (CuSO4) induces the expression of HIF-1alpha as well as GPER and
VEGF in breast and hepatic cancer cells through the activation of the EGFR/ERK/c
fos transduction pathway. Worthy, the copper chelating agent TEPA and the ROS
scavenger NAC prevented the aforementioned stimulatory effects. We also
ascertained that HIF-1alpha and GPER are required for the transcriptional
activation of VEGF induced by CuSO4. In addition, in human endothelial cells, the
conditioned medium from breast cancer cells treated with CuSO4 promoted cell
migration and tube formation through HIF-1alpha and GPER. The present results
provide novel insights into the molecular mechanisms involved by copper in
triggering angiogenesis and tumor progression. Our data broaden the therapeutic
potential of copper chelating agents against tumor angiogenesis and progression.
PMID- 26415224
TI - Mitochondria-targeted antioxidant preserves contractile properties and
mitochondrial function of skeletal muscle in aged rats.
AB - Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia
associated with a loss of mass and activity of skeletal muscle. In addition to
energy deprivation, increased mitochondrial ROS damage proteins and lipids in
aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for
potential therapeutic strategies to delay sarcopenia. This study elucidates the
pharmacological efficiency of the new developed mitochondria-targeted ROS and
electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and
mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged
(29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four
weeks and contractile properties of single skeletal muscle fibres and activity of
mitochondrial ETC complexes were determined at the end of the treatment period.
XJB-treated old rats showed higher muscle contractility associated with
prevention of protein oxidation in both muscle homogenate and mitochondria
compared with untreated counterparts. XJB-treated animals demonstrated a high
activity of the respiratory complexes I, III, and IV with no changes in citrate
synthase activity. These data demonstrate that mitochondrial ROS play a causal
role in muscle weakness, and that a ROS scavenger specifically targeted to
mitochondria can reverse age-related alterations of mitochondrial function and
improve contractile properties in skeletal muscle.
PMID- 26415220
TI - The different roles of selective autophagic protein degradation in mammalian
cells.
AB - Autophagy is an intracellular pathway for bulk protein degradation and the
removal of damaged organelles by lysosomes. Autophagy was previously thought to
be unselective; however, studies have increasingly confirmed that autophagy
mediated protein degradation is highly regulated. Abnormal autophagic protein
degradation has been associated with multiple human diseases such as cancer,
neurological disability and cardiovascular disease; therefore, further
elucidation of protein degradation by autophagy may be beneficial for protein
based clinical therapies. Macroautophagy and chaperone-mediated autophagy (CMA)
can both participate in selective protein degradation in mammalian cells, but the
process is quite different in each case. Here, we summarize the various types of
macroautophagy and CMA involved in determining protein degradation. For this
summary, we divide the autophagic protein degradation pathways into four
categories: the post-translational modification dependent and independent CMA
pathways and the ubiquitin dependent and independent macroautophagy pathways, and
describe how some non-canonical pathways and modifications such as
phosphorylation, acetylation and arginylation can influence protein degradation
by the autophagy lysosome system (ALS). Finally, we comment on why autophagy can
serve as either diagnostics or therapeutic targets in different human diseases.
PMID- 26415225
TI - The BET bromodomain inhibitor, JQ1, facilitates c-FLIP degradation and enhances
TRAIL-induced apoptosis independent of BRD4 and c-Myc inhibition.
AB - Inhibition of BET bromodomains (BRDs) has emerged as a promising cancer
therapeutic strategy. Accordingly, inhibitors of BRDs such as JQ1 have been
actively developed and some have reached clinical testing. However, the
mechanisms by which this group of inhibitors exerts their anticancer activity,
including induction of apoptosis, have not been fully elucidated. This report
reveals a previously uncovered activity of JQ1 in inducing c-FLIP degradation and
enhancing TRAIL-induced apoptosis. JQ1 potently decreased c-FLIP (both long and
short forms) levels in multiple cancer cell lines without apparently increasing
the expression of DR5 and DR4. Consequently, JQ1, when combined with TRAIL,
synergistically induced apoptosis; this enhanced apoptosis-inducing activity
could be abolished by enforced expression of ectopic FLIPL or FLIPS. Hence it
appears that JQ1 decreases c-FLIP levels, resulting in enhancement of TRAIL
induced apoptosis. Inhibition of proteasome with MG132 prevented JQ1-induced c
FLIP reduction. Moreover, JQ1 decreased c-FLIP stability. Therefore, JQ1
apparently decreases c-FLIP levels through facilitating its proteasomal
degradation. Genetic inhibition of either BRD4 or c-Myc by knocking down their
expression failed to mimic JQ1 in decreasing c-FLIP and enhancing TRAIL-induced
apoptosis, suggesting that JQ1 induces c-FLIP degradation and enhances TRAIL
induced apoptosis independent of BRD4 or c-Myc inhibition. In summary, our
findings in this study highlights a novel biological function of JQ1 in
modulating apoptosis and warrant further study of the potential treatment of
cancer with the JQ1 and TRAIL combination.
PMID- 26415226
TI - Next generation sequencing in synovial sarcoma reveals novel gene mutations.
AB - Over 95% of all synovial sarcomas (SS) share a unique translocation, t(X;18),
however, they show heterogeneous clinical behavior. We analyzed multiple SS to
reveal additional genetic alterations besides the translocation. Twenty-six SS
from 22 patients were sequenced for 409 cancer-related genes using the
Comprehensive Cancer Panel (Life Technologies, USA) on an Ion Torrent platform.
The detected variants were verified by Sanger sequencing and compared to matched
normal DNAs. Copy number variation was assessed in six tumors using the Oncoscan
array (Affymetrix, USA). In total, eight somatic mutations were detected in eight
samples. These mutations have not been reported previously in SS. Two of these,
in KRAS and CCND1, represent known oncogenic mutations in other malignancies.
Additional mutations were detected in RNF213, SEPT9, KDR, CSMD3, MLH1 and ERBB4.
DNA alterations occurred more often in adult tumors. A distinctive loss of 6q was
found in a metastatic lesion progressing under pazopanib, but not in the
responding lesion. Our results emphasize t(X;18) as a single initiating event in
SS and as the main oncogenic driver. Our results also show the occurrence of
additional genetic events, mutations or chromosomal aberrations, occurring more
frequently in SS with an onset in adults.
PMID- 26415227
TI - The knockdown of H19lncRNA reveals its regulatory role in pluripotency and
tumorigenesis of human embryonic carcinoma cells.
AB - The function of imprinted H19 long non-coding RNA is still controversial. It is
highly expressed in early embryogenesis and decreases after birth and re
expressed in cancer. To study the role of H19 in oncogenesis and pluripotency, we
down-regulated H19 expression in vitro and in vivo in pluripotent human embryonic
carcinoma (hEC) and embryonic stem (hES) cells. H19 knockdown resulted in a
decrease in the expression of the pluripotency markers Oct4, Nanog, TRA-1-60 and
TRA-1-81, and in the up-regulation of SSEA1; it further attenuated cell
proliferation, decreased cell-matrix attachment, and up-regulated E-Cadherin
expression. SCID-Beige mice transplanted with H19 down-regulated hEC cells
exhibited slower kinetics of tumor formation, resulting in an increased animal
survival. Tumors derived from H19 down-regulated cells showed a decrease in the
expression of pluripotency markers and up-regulation of SSEA-1 and E-cadherin.
Our results suggest that H19 oncogenicity in hEC cells is mediated through the
regulation of the pluripotency state.
PMID- 26415229
TI - A genome wide transcriptional model of the complex response to pre-TCR signalling
during thymocyte differentiation.
AB - Developing thymocytes require pre-TCR signalling to differentiate from CD4-CD8-
double negative to CD4+CD8+ double positive cell. Here we followed the
transcriptional response to pre-TCR signalling in a synchronised population of
differentiating double negative thymocytes. This time series analysis revealed a
complex transcriptional response, in which thousands of genes were up and down
regulated before changes in cell surface phenotype were detected. Genome-wide
measurement of RNA degradation of individual genes showed great heterogeneity in
the rate of degradation between different genes. We therefore used time course
expression and degradation data and a genome wide transcriptional modelling
(GWTM) strategy to model the transcriptional response of genes up-regulated on
pre-TCR signal transduction. This analysis revealed five major temporally
distinct transcriptional activities that up regulate transcription through time,
whereas down-regulation of expression occurred in three waves. Our model thus
placed known regulators in a temporal perspective, and in addition identified
novel candidate regulators of thymocyte differentiation.
PMID- 26415228
TI - Low-dose ionizing radiation induces mitochondrial fusion and increases expression
of mitochondrial complexes I and III in hippocampal neurons.
AB - High energy ionizing radiation can cause DNA damage and cell death. During
clinical radiation therapy, the radiation dose could range from 15 to 60 Gy
depending on targets. While 2 Gy radiation has been shown to cause cancer cell
death, studies also suggest a protective potential by low dose radiation. In this
study, we examined the effect of 0.2-2 Gy radiation on hippocampal neurons. Low
dose 0.2 Gy radiation treatment increased the levels of MTT. Since hippocampal
neurons are post-mitotic, this result reveals a possibility that 0.2 Gy
irradiation may increase mitochondrial activity to cope with stimuli. Maintaining
neural plasticity is an energy-demanding process that requires high efficient
mitochondrial function. We thus hypothesized that low dose radiation may regulate
mitochondrial dynamics and function to ensure survival of neurons. Our results
showed that five days after 0.2 Gy irradiation, no obvious changes on neuronal
survival, neuronal synapses, membrane potential of mitochondria, reactive oxygen
species levels, and mitochondrial DNA copy numbers. Interestingly, 0.2 Gy
irradiation promoted the mitochondria fusion, resulting in part from the
increased level of a mitochondrial fusion protein, Mfn2, and inhibition of Drp1
fission protein trafficking to the mitochondria. Accompanying with the increased
mitochondrial fusion, the expressions of complexes I and III of the electron
transport chain were also increased. These findings suggest that, hippocampal
neurons undergo increased mitochondrial fusion to modulate cellular activity as
an adaptive mechanism in response to low dose radiation.
PMID- 26415230
TI - SP600125 has a remarkable anticancer potential against undifferentiated thyroid
cancer through selective action on ROCK and p53 pathways.
AB - Thyroid cancer is the most common endocrine malignancy with increasing incidence
worldwide.The majority of thyroid cancer cases are well differentiated with
favorable outcome. However, undifferentiated thyroid cancers are one of the most
lethal human malignancies because of their invasiveness, metastatization and
refractoriness even to the most recently developed therapies.In this study we
show for the first time a significant hyperactivation of ROCK/HDAC6 pathway in
thyroid cancer tissues, and its negative correlation with p53 DNA binding
ability.We demonstrate that a small compound, SP600125 (SP), is able to induce
cell death selectively in undifferentiated thyroid cancer cell lines by
specifically acting on the pathogenic pathways of cancer development. In detail,
SP acts on the ROCK/HDAC6 pathway involved in dedifferentiation and invasiveness
of undifferentiated human cancers, by restoring its physiological activity level.
As main consequence, cancer cell migration is inhibited and, at the same time,
cell death is induced through the mitotic catastrophe. Moreover, SP exerts a
preferential action on the mutant p53 by increasing its DNA binding ability. In
TP53-mutant cells that survive mitotic catastrophe this process results in p21
induction and eventually lead to premature senescence. In conclusion, SP has been
proved to be able to simultaneously block cell replication and migration, the two
main processes involved in cancer development and dissemination, making it an
ideal candidate for developing new drugs against anaplastic thyroid cancer.
PMID- 26415231
TI - Cancer stem cells are the cause of drug resistance in multiple myeloma: fact or
fiction?
AB - Multiple myeloma (MM) remains a largely incurable, genetically heterogeneous
plasma-cell malignancy that contains - just like many other cancers - a small
fraction of clonogenic stem cell-like cells that exhibit pronounced self-renewal
and differentiation capacities, but also pronounced drug resistance. These MM
stem cells (MMSCs) are a controversial but highly significant issue in myeloma
research because, in our opinion, they are at the root of the failure of anti
neoplastic chemotherapies to transform myeloma to a manageable chronic disease.
Several markers including CD138-, ALDH1+ and SP have been used to identify MMSCs;
however, no single marker is reliable for the isolation of MMSC. Nonetheless, it
is now known that MMSCs depend on self-renewal and pro-survival pathways, such as
AKT, Wnt/beta-catenin, Notch and Hedgehog, which can be targeted with novel drugs
that have shown promise in pre-clinical and clinical trials. Here, we review the
pathways of myeloma "stemness", the interactions with the bone marrow
microenvironment that promote drug resistance, and the obstacles that must be
overcome to eradicate MMSCs and make myeloma a curable disease.
PMID- 26415232
TI - The predictive value of centre tumour CD8+ T cells in patients with
hepatocellular carcinoma: comparison with Immunoscore.
AB - The increasing evidences suggest that Immunoscore(IS), a combinatorial density
analysis of CD8+ and CD3+ cells in the centre and invasive margin of tumour (CT
and IM), has an advantage over the currently used tumour staging methods in a
variety of tumours; however, IS in hepatocellular carcinoma remains unreported.
In this study, IS was performed on serial sections from two HCC cohorts (total
449) and compared with current tumour staging systems. Kaplan-Meier curves
illustrate a positive association between a higher IS (IS>=2) and longer survival
of HCC patients. Although the IS was highly related to the outcome of patients,
however, IS seems not to be the optimal prognostic factor when compared with the
CD8CT. As noted, among CD8CT, CD8IM, CD3CT, CD3IM and IS, CD8CT, as an
independent indicator, demonstrated the highest prognostic impact on both DFS and
OS in our Cox multivariate regression analysis (P< 0.0001). In our study, the
minimum cut-off value was 93 CD8CT cells per mm2, to be used to divide the
patients into CD8CTHi group and CD8CTLo group in clinical settings. Our results
suggest that CD8CT densities analysis notably improved the accuracy of survival
prediction with convenience of clinical manipulation in HCC.
PMID- 26415233
TI - Retrograde TrkAIII transport from ERGIC to ER: a re-localisation mechanism for
oncogenic activity.
AB - In human SH-SY5Y neuroblastoma (NB) cells, nascent immature N-glycosylated 110kDa
TrkA moves rapidly from the endoplasmic reticulum (ER) to the Golgi Network (GN),
where it matures into the 140kDa receptor prior to being transported to the cell
surface, creating GN and cell surface pools of inactive receptor maintained below
the spontaneous activation threshold by a full compliment of inhibitory domains
and endogenous PTPases. In contrast, the oncogenic alternative TrkAIII splice
variant is not expressed at the cell surface but re-localises to intracellular
membranes, within which it exhibits spontaneous ERGIC/COPI-associated activation
and oncogenic Akt signalling. In this study, we characterise the mechanism
responsible for TrkAIII re-localisation. Spontaneous TrkAIII activation,
facilitated by D4 IG-like domain and N-glycosylation site omission, increases
spontaneous activation potential by altering intracellular trafficking,
inhibiting cell surface expression and eliminating an important inhibitory
domain. TrkAIII, spontaneously activated within the permissive ERGIC/COPI
compartment, rather than moving in an anterograde direction to the GN exhibits
retrograde transport back to the ER, where it is inactivated. This sets-up self
perpetuating TrkAIII re-cycling between the ERGIC and ER, that ensures continual
accumulation above the spontaneous activation threshold of the ERGIC/COPI
compartment. This is reversed by TrkA tyrosine kinase inhibitors, which promote
anterograde transport of inactivated TrkAIII to the GN, resulting in GN
associated TrkAIII maturation to a 120kDa species that is degraded at the
proteasome.
PMID- 26415235
TI - Surgical Services in Critical Access Hospitals, 2011.
AB - In this policy brief we describe the types and volume of major surgical services
provided in the inpatient and outpatient settings of Critical Access Hospitals
(CAHs) in 2011. Major surgical services are those procedures that require use of
an operating room (OR), regardless of whether the procedure was inpatient or
outpatient. Key Findings (1) CAH discharges of patients having a major surgical
procedure that required use of an OR were analyzed from four regionally
representative states: Colorado, North Carolina, Vermont, and Wisconsin. The
average surgical volume among all CAHs in the sample was 624 procedures per CAH
per year, and only 6.8 percent of CAHs performed none. (2) The average portion of
all surgery volume performed on an outpatient basis in CAHs is 77 percent.
Inpatient procedure volume ranged between 20 percent and 24 percent of total
surgical volume across the four states. Most of the research literature on
surgery in CAHs focus on inpatient procedures only, thus missing a significant
portion of the surgery volume that CAHs perform. (3) The high correlation (0.86,
p <0.0001) indicates that the 3:1 ratio of outpatient-to-inpatient surgical
volume was relatively consistent across CAHs. (4) Operations on the
musculoskeletal system, the eye, and the digestive system accounted for 67
percent on average of all surgical procedures in CAHs. Many surgical procedures
are performed on an inpatient and outpatient basis, but some are performed
exclusively in one setting.
PMID- 26415236
TI - [Long non-coding RNA and disease].
PMID- 26415238
TI - I extend a heartfelt.
PMID- 26415237
TI - [Current topics for sports medicine: knee joint surgery under arthroscope].
PMID- 26415234
TI - Deconvoluting the complexity of autophagy and Parkinson's disease for potential
therapeutic purpose.
AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by the
preferential death of dopaminergic neurons. In the past two decades, great
progress has been made toward understanding the pathogenesis of PD; however, its
precise pathogenesis still remains unclear. Recently, accumulating evidence has
suggested that macroautophagy (herein referred to as autophagy) is tightly linked
to PD. Dysregulation of autophagic pathways has been observed in the brains of PD
patients and in animal models of PD. More importantly, a number of PD-associated
proteins, such as alpha-synuclein, LRRK2, Parkin and PINK1 have been further
revealed to be involved in autophagy. Thus, it is now acknowledged that
constitutive autophagy is essential for neuronal survival and that dysregulation
of autophagy leads to PD. In this review, we focus on summarizing the
relationships amongst PD-associated proteins, autophagy and PD. Moreover, we also
demonstrate some autophagy-modulating compounds and autophagic microRNAs in PD
models, which may provide better promising strategies for potential PD therapy.
PMID- 26415239
TI - [Individual medicine-the present and the future].
PMID- 26415240
TI - [Treatment of leukemia and lymphoma: from the past to the future].
PMID- 26415241
TI - stARTing cART now! HIV treatment Italian Guidelines Update Dec. 2014.
PMID- 26415242
TI - Entering the age of 'ultra-superovulation'.
PMID- 26415243
TI - Distinctive hair helps ants stay cool.
PMID- 26415244
TI - Moon jellies rearrange to restore symmetry.
PMID- 26415245
TI - Authors' responses.
PMID- 26415246
TI - My Greatest Gift.
PMID- 26415247
TI - Words and Deeds: Advocacy and Our Code of Ethics.
PMID- 26415248
TI - Nurses Share Concerns about Achieving Quality Patient Outcomes.
PMID- 26415249
TI - Infusion Therapy Nurse a Leader and Advocate throughout her Long Career.
PMID- 26415250
TI - Continuing our Work to Support Nurse Practitioners.
PMID- 26415251
TI - Sacred Heart Nurses and Hospitalists Go Public with Staffing Concerns.
PMID- 26415252
TI - ONA's 2015 Legislative Agenda. .
PMID- 26415253
TI - The Modern School Nurse.
PMID- 26415254
TI - Blood Donors Deserve Nursing Expertise.
PMID- 26415255
TI - Advocate Profile: Steve Rooney, RN.
PMID- 26415256
TI - Advocate Profile: Rob Campbell, RN.
PMID- 26415257
TI - Advocate Profile: Virginia Smith, BSN, RN-BC.
PMID- 26415258
TI - [INDICATORS OF QUALITY OF ENDOSCOPY DEPARTMENTS (CABINET) ACTIVITIES].
AB - The article presents the possible indicators of quality of endoscopy departments
(cabinet) activities, developed on the basis of the experience of foreign
colleagues using information resource: PubMed, Cochrane Library, MDConsult,
DynaMed, Google Schola and search engine TRIP Database www.tripdatabase.com,
existing regulations as well as their own experience.
PMID- 26415259
TI - [ENDOCYTOSCOPY--NOVEL ENDOSCOPIC DIAGNOSTICS APPROACH: PRINCIPLES AND PROCEDURE].
AB - Endocytoscopy is one of the most novel endoscopic diagnostic procedures,
providing optical magnification up to 1150 times of gastrointestinal and
respiratory tract mucosa. Such approach allows real-time tissue and cellular
structure visualization. Endocytoscopy, along with confocal laser endomicroscopy,
can be considered as "optical biopsy" in vivo. Of course, endocytoscopy currently
is experimental diagnostic method, all available endocytoscopes are prototypes.
According to published data, endocytoscopy can be used in precancerous conditions
and early intramucosal cancer diagnostics in esophagus, stomach, colon and
bronchial tree. Different types of endocytoscopes are used for examinations: some
of them are baby-scopes, with fixed magnification 570-1150 times, introduced into
accessory channel of the therapeutic parent-endoscope, others--are integrated
type, providing scalable magnification from 80 to 380 times. As for traditional
pathology ex vivo, for endocytoscopy mucosal cell nuclei stain is needed. For
vital staining during endocytoscopy methylene blue, toluidine blue and crystal
violet in different concentrations are more often used. In cases of squamous-cell
dysplasia or cancer, it is recommended to use 1% methylene blue solution, whereas
in intestinal type metaplasia, dysplastic changes and cancer (Barrett's
esophagus, P. Correa precancerous cascade, colon adenomas), 1% toluidine blue is
preferred. With endocytoscopy, after vital staining, we can visualize and
estimate mucosa tissue and cell characteristics: papillae, crypt and gland shapes
and sizes, their integrity (tissue markers); cell nuclei size and shape, polarity
and nuclear dye intensity (cell markers).
PMID- 26415260
TI - [ENDOSONOGRAPHY IN THE DIFFERENTIAL DIAGNOSIS OF THE COMMON BILE DUCT STENOSIS].
AB - The article states the results of examination and treatment of 57 patients with
stenosis of the common bile duct of various genesis. The main aim of the work is
criteria definition and evaluation of diagnostic significance of endosonography
in the differential diagnosis of benign and malignant common bile duct stenosis.
The paper presents a methodology of endoscopic ultrasound and basic criteria for
the differential diagnosis of tumors and other lesions of the extrahepatic bile
ducts. A comparative analysis of endosonography, ultrasound, CT, MRCP was
conducted. The sensitivity of endosonography in determining the nature of the
common bile duct stenosis was 97.7%, a specificity 100% and accuracy 98.2%, which
is superior to other methods of radiological diagnosis. In comprehensive surgical
centers endosonography should be used as a method of specifying the final
diagnosis to determine the nature of the common bile duct stenosis, particularly
at low constriction location.
PMID- 26415261
TI - [POSSIBILITY OF EARLY GASTRODUODENOSCOPY IN ASSESSING OF SEVERITY AND LOCATION OF
THE NECROSIS IN ACUTE BILE PANCREATITIS].
AB - In prospective cohort study of 100 patients with acute bile pancreatitis studied
endoscopic upper gastrointestinal changes depending on the location of the zone
of inflammation and necrosis in the pancreas and the severity of the
pancreatitis. In the overall structure changes were the most common finding of a
violation of lymphflow--lymphangiectasia--67%. From 29% to 44% of patients had
evidence of acute inflammation in the stomach and duodenum. Every fourth patient
noted pain in moving the endoscope in the stomach or duodenum. However, direct
signs of obstructive acute bile pancreatitis occurred in only 7% - 15% of cases,
although extended intramural bile duct as a sign of bile hypertension occurred in
25% of cases. Revealed significant differences in the frequency of endoscopic
evidence of the localization of necrosis in the head, body or tail of the
pancreas. Also revealed significant differences in the structure of endoscopic
findings in depending on the severity of the pancreatitis. It is shown that
direct signs of obstructive bile pancreatitis is not related to the localization
of inflammation, but have a close relationship with the severity of bile
pancreatitis. Thus, a qualified assessment of upper gastrointestinal changes in
acute bile pancreatitis can improve the topical diagnosis of necrosis in the
pancreas and the early evaluation of the severity of bile pancreatitis.
PMID- 26415262
TI - [ENDOSCOPIC DIAGNOSIS AND PARIETAL IMPEDANCOMETRY IN THE ASSESSMENT OF CHANGES IN
THE MUCOSA OF THE DUODENUMIN PATIENTS WITH SUSPICION ON POSTCHOLECYSTECTOMY
SYNDROME].
AB - The article is based on analysis of the results of continuous cohort study of 79
patients. All patients underwent endoscopic examination of the upper parts of the
gastrointestinal tract and parietal impedancometry mucosa in the descending part
of the duodenum. The aim of the study was to determine the effectiveness of
endoscopy and the parietal impedancometry mucosa of the duodenum in patients with
suspected development of postcholecystectomy syndrome. In the result of the
analysis revealed that the overall structure of endoscopic changes in patients
with gallstone disease and after cholecystectomy is the most common signs of
chronic pancreatitis. The highest values of the impedance of the mucosa in
patients with gallstones.
PMID- 26415263
TI - [ULTRASONIC DIAGNOSIS OF GIRSHPRUNG ILLNESS AT CHILDREN].
AB - Use of ultrasonic diagnostics reduces number of the low-informative, invasive and
connected with beam loading procedures. Objectivity of results of ultrasonic
structure of an intestinal wall depends on many subjective parameters: from the
device on which examination, from the expert experience, from extent of
preparation of intestines, from the applied solution for contrasting, from degree
of expressiveness of a desire on a defecation is conducted when filling a thick
gut.
PMID- 26415264
TI - [VASCULAR ENDOTHELIAL GROWTH FACTOR AND SOME INDICATORS OF ENDOTHELIAL
DYSFUNCTION OF PATIENTS HAVING CHRONIC INFLAMMATORY DISEASES OF THE GASTRO
DUODENAL ZONE].
AB - The aim of the study was to determine the content of vaskuloendotelian growth
factor and nitric oxide in children with chronic inflammatory diseases of the
stomach and duodenum. The study involved 63 children with chronic inflammatory
diseases of the gastroduodenal zone. Substrate study was serum. The data obtained
were compared with a group of healthy children. The highest possible content
vaskuloendotelian growth factor noted in the group of children with duodenal
ulcer in the acute phase and in the group of chronic gastroduodenita associated
with Helicobacter pylori. According to the results of the study established the
role of nitric oxide and vaskuloendotelian growth factor in the pathogenesis of
gastroduodenal diseases.
PMID- 26415265
TI - [AETIOLOGY AND PATHOGENESIS GASTRO-DUODENALES ULCERATIVE LESIONS IN ELDERLY].
AB - In review today conceptions of view to aetiology and pathogenesis gastro
duodenales ulcerative lesions in elderly. Atherosclerosis, ischemic disease of
the heart and hypertension are reasons of acute ulcers and erosions in elderly.
The breaking of microcirculation are very importance.
PMID- 26415266
TI - [ENDOSCOPIC MUCOSAL RESECTION WITH SUBMUCOSAL DISSECTION ESD AND THE FIRST LONG
TERM RESULTS OF APPLYING THIS METHOD].
AB - This review discusses the advantages and disadvantages of endoscopic mucosal
resection with submucosal dissection ESD and the first long-term results of
applying this method.
PMID- 26415267
TI - [DEONTOLOGICAL QUESTIONS IN PROPHYLACTIC OF ENDOSCOPIC COMPLICATIONS: THE
SIGNIFICANCE OF RATIONAL AND PSYCHOLOGICAL FACTORS (analytical overview)].
AB - THE AIM OF STUDY: To evaluate the ways of reduction complications during
endoscopic procedures based on principals of professional ethics and improving
the quality of working area. MATERIALS AND METHODS: Data of fundamental
literature, evidence based medicine, science publications and internet portals.
RESULTS: Deontology is the fundamental principle of medical practice and one of
the main factors of professional effectiveness. Complications in endoscopy are
often the investigations of deviation from the deontological principals. The
whole number of psychological factors influences on professional activity of
endoscopists, where the emotional "burn-out" syndrome (EBS) occupies one of the
main places. Prophylactic and timely relief of EBS serves improvement of the
practical work quality. CONCLUSION: Creation of favorable working area is the
strategically important task in prophylactics of endoscopy complications. The
questions of practical realization of deontological principles in endoscopy are
the subject of further discussion.
PMID- 26415268
TI - [ANALYSIS OF THE RESULTS OF ENDOSCOPIC AND MORPHOLOGICAL STUDIES OF THE STOMACH
MUCOSA WITH REDUCED PEPSINOGEN-I IN PATIENTS WITH H. PYLORI (H.P.)--ASSOCIATED
GASTRITIS IN TOMSK AND TOMSK REGION].
AB - AIM OF INVESTIGATION: To explore and describe the endoscopic picture of HP-
associated atrophic gastritis and to analyze the specificity of endoscopic
markers indicating the presence of atrophic gastritis, intestinal metaplasia and
dysplasia using high-tech methods of endoscopy in comparison with morphological
characteristics of atrophic gastritis defining the degree of activity and stage
of atrophic gastritis according to the system OLGA. MATERIALS AND METHODS: 40
people: males and females aged 40 to 70 years with a reduced level of pepsinogen
I and a positive titre of antibodies to H. pylori in serum--were included into
the study. THE RESULTS: Risk groups with atrophic gastritis based on indicators
of pepsinogen 1 were formed. Endoscopic picture of H. Pylori--associated atrophic
gastritis in patients with reduced level of pepsinogen I in serum is studied and
described. Analysis of the specificity of endoscopic markers indicating the
presence of AG, intestinal metaplasia and dysplasia using high-tech methods of
endoscopy (endoscopy with high resolution, magnifying endoscopy, chromoendoscopy
and narrow band imaging endoscopy (NBI) is made. Analysis of their sensitivity in
comparison with the results of morphological studies of biopsy material is made.
CONCLUSION: Thus, these studies show that high-resolution endoscopy in
combination with magnification and chromoendoscopy allows accurately identify
areas of atrophy, intestinal.Narrow band imaging endoscopy (NBI) provides a
detailed picture of the vascular pattern of tissues, pattern changes typical for
pathological areas of inflammatory genesis, as well as for precancers and early
cancers. All these methods have high sensitivity and specificity in the diagnosis
of HP-associated atrophic gastritis in comparison with the results of
morphological studies of biopsy materials of stomach mucosa.
PMID- 26415269
TI - [STENTING VERSUS PALLIATIVE SURGERY IN PATIENTS WITH MALIGNANT GASTROINTESTINAL
STENOSIS].
AB - AIM: Retrospective analysis of the results of stenting versus surgical palliation
in patients with malignant gastrointestinal stenosis. MATERIAL AND METHODS: 85
patients underwent endoscopic stenting (41) or surgical intervention (44). Level
of stenosis: gastric outlet (23/38), multi-level gastric obstruction (2/3),
duodenum or jejunum (12/3), gastrojejunoanastomosis (3/0) and
gastroduodenoanastomosis (1/0). 49 self-expanding metal stents were implanted in
41 patients. 41 gastroenteroanastomoses and 3 jejunostomas were performed in
surgical group. RESULTS: Stents were successfully inserted in all patients. Early
complications were observed in 3 (7.3%) patients after stenting and in 9 (20.5%)
after surgical palliation, p = 0.0755. Postoperative lethality was 2,4% (1
patient) after stenting and 31.8% (14 patients) after surgery, p = 0.0003. Mean
hospital stay was 15 days in stenting group and 23 days in surgical group, p <
0.001. There was no statistically significant difference in long-term results,
neither in late complications (p = 0.3691), nor in survival (p =0.3697).
CONCLUSION: Endoscopic placement of self-expanding stents is an effective method
of restoration of oral intake in patients with malignant gastrointestinal
obstruction. Stenting is associated with equal rates of early and late
complications, lower mortality and decreased in-hospital stay as compared with
surgery, and therefore may be recommended as a final palliation in inoperable
patients.
PMID- 26415271
TI - [PSYCHOSOMATIC RELATIONSHIPS DURING GASTROINTESTINAL DISEASE ON THE MODEL OF
IRRITABLE BOWEL SYNDROME].
AB - On the model of irritable bowel syndrome basic concept of psychosomatic
relationships in diseases of the gastrointestinal tract and main methods of
treatment tailored to their specific effects on the gastrointestinal tract are
analyzed.
PMID- 26415270
TI - [Using "Collegel" complex in combined therapy of rectum cancer].
AB - The method of drug delivery to the site of lesion is an important component of
drug effectiveness. To maximize the effectiveness of drugs LLC "Koletex" has
developed and brought into practice the drug, "Collegel" for directed drug
delivery. Hydrogel based composition "Collegel" is biopolymer consists of sodium
alginate. In the gel-forming polymer one or more substance introduced on a
specific technology. Studies have been conducted to examine the possibility of
using hydrogel "Collegel" with 5-fluorouracil as radiomodifying agent in the
treatment of rectal cancer. In the group of patients who received intrarectal
introduction 5-fluorouracil, metastases were observed significantly less
frequently (2.8%) than in the group of patients who received surgical treatment
(15.2%) and preoperative radiotherapy in monoregimen (12.6%), as well as reduced
doses capecitabine concomitantly with preoperative radiotherapy (11.4%), which
gives the basis for the use of intrarectal way of introduction of therapeutic
doses of 5-fluorouracil during preoperative chemoradiation therapy. The newly
created method of complex treatment of patients with rectal cancer to ensure
adequate local control of the disease. There is no local recurrence diagnosed
over the 2-year follow-up period. We have considerable experience in the
application of gel "Collegel" containing antioxidant and immunomodulator
"Derinat" (deoxyribonuclease sodium) for the prevention and treatment of
radiation damage to normal tissues during radiotherapy of malignant tumors.
Patients can be treated without interruption and significantly reduces the
incidence of adverse radiation damage.
PMID- 26415272
TI - [PRINCIPLES OF POSTOPERATIVE DRUG THERAPY OF COMPLICATED DUODENAL ULCERS].
AB - The article highlights the principles of individualized drug therapy of
complicated duodenal ulcers in the postoperative period, based on the removal of
the pathophysiological changes that occurred after different types of medical or
surgical benefits.
PMID- 26415273
TI - [ESOPHAGITIS, CAUSED BY HERPES SIMPLEX VIRUS: CASE REPORT].
AB - The clinical observation of the patient at the age of 56 years, with lesions of
the esophagus by the herpes simplex virus has been presented. The patient
complained of odynophagia and dysphagia. Treatment with proton pump inhibitors in
outpatient stage was not effective. On endoscopic examination revealed multiple
ulcers in all parts of the esophagus. Herpes simplex virus has been detected in
biopsy specimens of esophageal mucosa by the PCR method. Treatment with acyclovir
led to rapid and complete clinical recovery. Analysis of the literature allowed
making the conclusion about the importance and actuality this demonstration.
PMID- 26415275
TI - [Experimental Evidence of Proliferation and Reproduction of Highly Differentiated
Sertoli Cells].
AB - The main results of studies regarding the biology of Sertoli cells under various
experimental conditions are considered. Possible potential mechanisms underlying
the transition of highly differentiated Sertoli cells to dedifferentiation,
limited by proliferation and reproduction and not accompanied by significant
phenotypic changes, are discussed.
PMID- 26415274
TI - [A Cellular Automata Model for a Community Comprising Two Plant Species of
Different Growth Forms].
AB - A cellular automata computer model for the interactions between two plant species
of different growth forms--the lime hairgrass Deschampsia caespitosa (L.) P.
Beauv., a sod cereal, and the moneywort Lysimachia nummularia L., a ground
creeping perennial herb--is considered. Computer experiments on the self
maintenance of the populations of each species against the background of a
gradual increase in the share of randomly eliminated individuals, coexistence of
the populations of two species, and the effect of the phytogenous field have been
conducted. As has been shown, all the studied factors determine the number of
individuals and self-sustainability of the simulated populations by the degree of
their impact. The limits of action have been determined for individual factors;
within these limits, the specific features in plant reproduction and dispersal
provide sustainable coexistence of the simulated populations. It has been
demonstrated that the constructed model allows for studying the long-term
developmental dynamics of the plants belonging to the selected growth forms.
PMID- 26415276
TI - [Metabolites of Toxigenic Fungi in Lichens of Genera Alectoria, Bryoria, Evernia,
Pseudevernia, and Usnea].
AB - Complexes of mycotoxins in fruticose lichens of 14 species belonging to five
genera of the family Parmeliaceae were characterized by size, composition, and
content of individual components. It was shown that species of the genus Bryoria
always contain five mycotoxins (sterigmatocystin, mycophenolic acid, citrinin,
emodin, and alternariol). In Evernia and Pseudevernia, this list is supplemented
with zearalenone, diacetoxyscirpenol, and cyclopiazonic acid or fumonisins. It
was noted that Alectoria and Usnea are distinguished by a peculiar set of toxic
metabolites and occupy an intermediate position according to their number. The
similarities and distinctions of the mycotoxin profile in species belonging to
the same genus and in specimens from different habitats are discussed.
PMID- 26415277
TI - [Effect of Genotype and Medium Culture Content on Microspore-Derived Embryo
Formation in Chinese Cabbage (Brassica rapa ssp. chinensis) Cv. Lastochka].
AB - The influence of different factors on microspore embryogenesis in Chinese cabbage
(B. rapa ssp. chinensis) was studied. A genotype dependence for embryo formation
was observed. The majority of embryos and plants were obtained from microspores
isolated from flower buds (2-2.9 mm in length) and cultured in the NLN liquid
medium with 13% sucrose (w/v) supplemented with 24-epibrassinolide and 1%
activated charcoal. Embryos cultured on the 1/2 Murashige-Skoog culture medium
with 2% sucrose (w/v), 0.1 mg/L benzylaminopurine, and 3g/L Phytagel stimulated
the formation of secondary embryos that resulted in development of large number
of doubled haploid plants.
PMID- 26415278
TI - [The Stimulating Effect of Exometabolites of the Marine Microalgae Phaeodactylum
tricornutum Bohlin on Reproduction of Listeria monocytogenes].
AB - The biological activity of ethyl acetate extract of exometabolites from the
marine microalgae Phaeodactylum tricornutum against a test culture of Listeria
monocytogenes 4b has been investigated. It was shown that the stimulating effect
of algal exometabolites on the growth of pathogenic bacteria increased maximally
by 98.3% on day 6 of the cultivation, if the active substances comprising the
culture liquid of P. tricornutum were separated by successive extractions with
solvents in order of increasing polarity (hexane, benzene, ethyl acetate), and by
150% on day 3, if the substances from the ethyl acetate extract of exometabolites
were separated by column chromatography. It is noted that the fraction of
biologically active substances maximally stimulating the growth of L.
monocytogenes can be used to prepare an accumulation medium for detecting these
patho- genic bacteria in marine environments and hydrobionts.
PMID- 26415279
TI - [Biomorphological Features and Microevolution of the Invasive Species Bidens L.
in European Russia].
AB - Species of the genus Bidens that have invaded natural communities in Europe were
observed. Fourteen species have been introduced in European botanical gardens
since the 18th century, but only two of them have become invasive in Russia
Bidensfrondosa and B. connata. B.frondosa demonstrates microevolutional ability
in the second distribution range. Nevertheless, it has a low ability of
hybridization. B. frondosa has higher competitiveness compared with that of B.
connata.
PMID- 26415280
TI - [Contractile Tone and Contraction as Important Physiological Properties of
Terminals on the Processes of Living Neurons].
AB - An attempt to summarize some static morphological renderings of reversible
structural alterations of nervous processes, as well as receptor and synaptic
terminals, to compare them with the mechanisms of actual transformation of living
neurons and to find a common kinetic characteristic for these phenomena has been
made. The contractile tone and contraction of processes of living isolated
neurons are reported. The dependence of the direction of retraction on the
localization of the adhesion site of the isolated cell has been detected. The
retraction bulb has been identified as an indicator of all contractions of motor
and sensory terminals, both alive and fixed. The process of transformation of
growth cones into retraction bulbs has been investigated. The presence of
mechanical tension in preterminals and interneuronal contacts has been
demonstrated in vitro. Similarity of the kinetics of tissue receptor sensory
terminals and growth cones has been detected during in vivo experiments. The
kinetics of asynaptic dendrite contraction has been compared to the well
characterized structural variability of dendritic spines. The hypothesis of a
common origin of the contractile tone of all nervous elements as one of the
principal nonelectrophysiological properties of a neuron has been put forward.
PMID- 26415281
TI - [Embryonic and Larval Development of the Asian Seabass Lates calcarifer (Pisces:
Perciformes: Latidae) under Thermostatically Controlled Conditions].
AB - Material for this study was obtained from the hatchery with brood stock of Lates
calcarifer that originated from a natural population living in inshore waters off
Central Vietnam. Commercial interest in L. calcarifer as an object of mariculture
and wildstock fishery has resulted in several publications on its early life
history; nevertheless, comprehensive description of early development of L.
calcarifer based on controlled incubation of embryos and larvae has remained
absent. In the present paper embryonic and larval development to the stage of
anlage of pelvic fins is described in detail and illustrated with original
drawings of live material on the basis of thermostatically controlled incubation
of embryos at 27 degrees C and larvae at 26.8 degrees C (26.5-28.0 degrees C).
The first cleavage furrow appeared at the age of 33.5 min. The duration of
synchronous cleavage cycle was 16 min. About 80% of all embryos hatched at the
age of 18 h. The length of newly hatched larva during the first hour after
emergence from the egg shell was 1.63 +/- 0.016 mm (1.50-1.75 mm). Chronology of
development of the organs, early circulatory system, and pigmentation pattern is
given. The dynamics of change in the trunk and caudal body segment number in
larva from hatching to the moment of anlage of pelvic fins is shown. The total
number of body segments reached the maximum value of 26-27 soon after hatching
and then decreased to 20-21 segments. Newly received data are discussed in a
comparative context of development of some other teleosts.
PMID- 26415283
TI - [Parental Care and Testosterone Secretion in Forest Rodent Males: Sensitization
and Androgenic Stimulation of Parental Behavior].
AB - The reaction of males of three forest rodent species (Myodes clethrionomys, M.
rutilus, Apodemus uralensis) to young animals in comparison with their
dimensional characteristics and androgenization level was studied. Demonstration
of parental care was detected in males of two vole species (M. clethrionomys and
M. rutilus) in case of regular contacts with them (sensitization effect). It was
demonstrated that the testosterone concentration in the blood serum, as well as
the testosterone content in the testicles of the M. clethrionomys males
(demonstrating the parental care), was higher than in the sample of males
inclined to infanticide. An increased testosterone content in the testicles and
blood serum was also found in the M. rutilus males that had contact with young
animas. Neither demonstration of parental care nor significant differences in the
testosterone concentration in the testicles and blood serum were detected in the
A. uralensis males.
PMID- 26415282
TI - [Content of Thyroid and Sex Steroid Hormones in Young-of-the-Year of Black Sea
Trout Salmo trutta labrax from Two Spatial Groups for Different Duration of
Starvation].
AB - The content of thyroid and sex steroid hormones is determined in fish-farm
juveniles of Black Sea trout 5.5 months old, from the bottom and pelagic spatial
groups differing in the probability of future selection of the resident or
anadromous life strategies, respectively. Differences in the concentration of the
aforementioned hormones are found in young-of-the-year corresponding to those in
the migratory and resident forms of yearlings of trout. In the juveniles from the
pelagic group at the age 0+, the level of triiodothyronine, thyroxine, and
testosterone is higher than in specimens from the bottom group. Prolonged
starvation results in a higher content of triiodthyronine, thyroxine, and
testosterone in the blood of juveniles from both spatial groups. The
concentration of estradiol-17beta increases in pelagic specimens and decreases in
bottom specimens.
PMID- 26415284
TI - [Biological Productivity of the Boguchanskoe Reservoir: Modeling and Prediction].
AB - A dynamic mass-balance model has been presented for the biotic energy flux in the
ecosystem of the Boguchanskoe Reservoir (Angara River, Irkutsk oblast). It has
been revealed that this model is controlled by the small number of input
parameters and is intended for prediction of the biomass and annual production of
primary producers, reducers, and consumers from various orders, including fish.
The model algorithm has been described.
PMID- 26415285
TI - [Morphophysiological and Behavioral Adaptations of Elk to Wintering].
AB - This paper studies morphometric parameters (body weight, weight of internal
organs, body size, etc.) in 170 elk of various sex and age obtained in the Vyatka
taiga area in winter. A number of physiological parameters (specific metabolism
and thermal conductivity, heat loss rate, etc.) characterizing the metabolic rate
and energy balance in the body were calculated for model animals (calf, male, and
female). It is noted that in the transition from the first to the second half of
winter the specific metabolism in model animals decreased from 20.6, 16.9, and
15.9 to 18.7, 15.4, and 14.5 kcal/(kg day), respectively. It is shown that
changes in the rhythm of motor activity of elk are synchronized with the daily
air temperature and the maximum flight distance depends on the amount of energy
received by the body with food.
PMID- 26415286
TI - [FUNCTIONAL CONDITION OF KIDNEYS IN NEWBORNS WITH CONGENITAL MALFORMATIONS IN THE
PERIOPERATIVE PERIOD].
AB - The article deals with results of the study of functional condition of kidneys in
newborns with congenital surgical pathology in the perioperative period. Serum
cystatin C and urine beta2-microglobulin were used as a marker of acute kidney
injury (AKI). The evaluation of parameters was given in dynamics--before and
after surgery, and on 1st, 5th and 10th postoperative day. We analyzed prospects
of using these markers in the diagnosis of AKI.
PMID- 26415287
TI - [OPTIMIZATION OF EARLY DIAGNOSIS OF ACUTE KIDNEY INJURY IN NEWBORNS IN CRITICAL
CONDITION].
AB - Current diagnosis of acute kidney injury (AKI) is one of the most pressing
problems in the newborn in critical condition. OBJECTIVE: To determine the
diagnostic value of indicators of renal blood flow as a marker of acute kidney
injury in critically ill newborns. MATERIALS AND METHODS: The study included 40
infants in critical condition. A clinical assessment of severity of the condition
during admission was carried out with Neonatal Multiple Organ Dysfunction Score
(NEOMOD) and Neonatal Therapeutic Intervention Scoring System (NTISS). All
patients underwent evaluation of clinical and instrumental parameters, including
ultrasound of the renal vessels, renal vascular resistance index and speed
performance. CONCLUSIONS: 1) biochemical markers used in routine clinical
practice were not sufficiently informative for the diagnosis of AKI. 2) For a
more accurate assessment of the risk of AKI using serum creatinine, GFR
calculation and evaluation on a scale RIFLE it is should be focused on
performance standards, appropriate for gestational age and birth weight. 3)
Evaluation of blood flow at a particular index in the resistance of the main
renal arteries had the greatest predictive value and had a relatively high
sensitivity and specificity for the diagnosis of AKI.
PMID- 26415289
TI - [THE DIFFICULTY IN DIAGNOSING OF RARE FORMS OF CONGENITAL DISORDERS OF AMINO ACID
METABOLISM IN INFANTS (HEREDITARY TYROSINEMIA)].
AB - Diagnosis of amino acid metabolism disorders according to the clinics without
laboratory diagnosis is almost impossible in infants with a history of neonatal
and/or premorbid background and multi-organ failure. Mortality due to hereditary
tyrosinemia type I is greater than 90%.
PMID- 26415288
TI - [LABORATORY MARKERS FOR EARLY DIAGNOSIS OF NEONATAL SEPSIS].
AB - Sepsis in neonates still remains difficult issue for clinicians. This review
observes literature data about early laboratory diagnosis of neonatal sepsis. The
paper considers the latest information about well-known methods of sepsis
diagnosis in neonates such as complete blood count, acute phase reactants,
cytokine markers, their advantages and disadvantages, as well as statistical
value based on different meta-analysis and large multicenter investigations in
many countries. We notified the newest methods in sepsis diagnosis such as plasma
amyloid A, DAMP molecules, cell surface markers CD64, CD11b, and inter-a
inhibitor proteins. The review informs about analysis of genomic and proteomic
profile, nucleic acids tools. This data considering for early and late neonatal
sepsis and their statistical values: sensitivity, specificity, positive and
negative predictive value.
PMID- 26415290
TI - [THE USE OF VOLATILE AGENTS FOR SEDATION IN CHILDREN IN THE INTENSIVE CARE UNIT].
AB - Sedation is a controllable level of medication depression of consciousness during
which protective reflexes, adequate breathing, and responsiveness to physical
stimuli and verbal commands are retained A number of physical and psychological
factors affect the psyche of patients in the intensive care unit. Central nervous
system (CNS) is a primary target of action of anesthetics and analgesics, and the
bi-spectral index reflects the level of sedation of CNS, regardless of what drug
caused sedation. The aim of this study was to use volatile anesthetics
sevoflurane and isoflurane in children for sedation in the intensive care unit.
Constant use of the inhalation route of administration helps to maintain the
desired level of sedation depth for the required period of time in patients who
are on long-term sedation and is practical for correction.
PMID- 26415291
TI - [DETERMINATION OF THE STATE OF MICROCIRCULATION BY MEANS OF COMPUTER
CAPILLAROSCOPY IN CHILDREN SEDATED WITH RETENTION OF CONSCIOUSNESS IN OUTPATIENT
PEDIATRIC DENTAL TREATMENT].
AB - Dental treatment of infants and pre-school children is challenging because of
high rate of dental fear General anesthesia is the only option for behavioral
control in this age group. In case of minor medical procedure physical restrain
is also used often enough aggravating the fear An alternate method for
comfortable treatment is monitored conscious sedation (MCS). Standard techniques
of monitoring do not always provide accurate determination of stress level in
children since the external stress manifestations may appear non-significant and
unobtrusive. Computer capillaroscopy (CC) allows real time evaluation of early
functional disorders at the microlevel and of anesthesia efficiency in vivo.
OBJECTIVE AND METHODS: The research involved 298 children. 256 of them were
treated under MCS and 42 constituted reference group treated without MCS. The
groups were also divided into subgroups according to age: 0-3 and 3-6 year olds.
Therapeutic and surgical treatment features were analyzed separately. MCS was
conducted by means of intramuscular injection of midazolam in dosages of 0.1,
0.15, and 0.2 mg per kg. BIS, arterial blood pressure, heart rate, respiratory
rate, and SpO2 were monitored at 4 stages while the following microcirculation
parameters were recorded by CC: density of capillary net, the size of arterial,
venous and transitional microcirculation links (ML), linear and volume bloodflow
velocity, perfusion balance. The obtained data were statistically processed and
analyzed with the use of Statistica Stat Soft 8.0 software. CONCLUSIONS: Children
undergoing dental treatment without MCS are affected by stress. The degree of
stress in surgical patients was noted to be significantly higher The absence of
physiological parameters changes in children treated without MSC is not a proof
of the absence of stress. The dose of 0.15 mg per kg is optimal for the
comfortable level of MSC. The increase of midazolam-dose over 0.15 mg per kg is
not associated with further reduction of stress. The obtained data is true for
both age categories.
PMID- 26415292
TI - [THE EXPERIENCE OF ANAESTHESIA MANAGEMENT FOR SENSING OF NASOLACRIMAL DUCT IN
CHILDREN].
AB - Despite low invasiveness, lacrimal passages, intubation in children requires
general anaesthesia to prevent traumatic and neurological complications. General
anaesthesia with sevoflurane is optimal for technical simplicity, safety and
controllability. Methods of face mask inhalation anesthesia with halothan and
sevoflurane were compared in 996 patients. The authors have developed their own
standart of performing the face mask inhalation anesthesia with sevoflurane in
children during lacrimal passages intubation. This allowed to minimize the number
of intra- and postoperative complications in children, to reduce period of
postanesthetic observation, to advance the peroral compensation of fluid deficit.
PMID- 26415293
TI - [PERIOPERATIVE MANAGEMENT IN PATIENTS WITH DISEASES OF THE CARDIOVASGULAR Yb I am
IN NON-CARDIAC SURGERY (Commentary on the new European guidelines "Non-cardiac
surgery: evaluation and management of cardiovascular system")].
AB - New guidelines for the perioperative management of patients with concomitant
diseases of the cardiovascular system (CVS) have been published in the beginning
of 2014. The guidelines were the result of joint work of the Board of experts of
the European society of cardiology (ESC) and European society of anaesthesiology
(ESA). Recommendations ESC/ESA-2014 thoroughly and accurately determine the
algorithm of actions of the anaesthesiologist in the process of preparation and
conduct of anesthesia and intensive therapy in the early postoperative period in
accordance with the modern level of development of our specialty. No doubt they
will be useful to all professionals involved in the process of providing medical
care to patients in non-cardiac surgery with concomitant diseases of the
cardiovascular system. This article, however, does not purport to be a complete
summary of the cited document; it only contains, its own commentary on those
provisions which are in the author's opinion the most significant and
interesting.
PMID- 26415294
TI - [EFFICACY AND SAFETY OF ROCURONIUM BROMIDE PRODUCED IN THE RUSSIAN FEDERATION: A
SINGLE-BLIND RANDOMIZED CLINICAL TRIAL].
AB - DESIGN: A single-blind comparative prospective randomised clinical trial.
OBJECTIVE: To evaluate the efficacy and safety of Russian muscular relaxant
(Kruarone) in comparison with Esmerone in multicomponent balanced anesthesia
during laparoscopic cholecystectomy. 80 patients (23-68 years old) were examined.
The patients were randomized into two equal groups. The results showed that
Kruarone was effective relaxant with rapid onset of action, providing optimal
conditions for muscle relaxation for laryngoscopy and tracheal intubation.
Kruarone did not require frequent administration supports, providing high quality
and stable neuromuscular blockade during surgery. There was no any one case of
adverse events for the entire period of 24-hour surveillance, the drug has no
cumulative effect. Kruarone did not cause allergic reactions and had no
significant effect on hemodynamics. Thus Kruarone 0.6 mg/kg with an average total
flow rate of the drug within 55 mg (39.6-75.43 mg) has the same effectiveness and
safety with Esmerone in similar dosages.
PMID- 26415295
TI - [MONITORING OF INTRACRANIAL PRESSURE IN PATIENTS WITH MASSIVE ISCHEMIC STROKE].
AB - PURPOSE OF THE STUDY: To assess the role of monitoring of intracranial pressure
(ICP) in patients with massive ischemic stroke within the first 5 days of the
onset of the disease. MATERIAL AND METHODS: We have analyzed the results of
monitoring of intracranial pressure in 10 patients with massive ischemic stroke
and compared dynamics of ICP with the dynamics of intracranial pressure and the
level of consciousness and dislocation of the brain according to CT RESULTS:
Dislocation syndrome decompensation occurred in 6 patients, of which only 3
patients had increased intracranial pressure greater than 20 mm Hg with
oppression of the level of consciousness to moderate coma and deeper The average
value of transverse dislocation in these patients at the same time amounted to 17
mm. In 2 patients with atrophy of the brain we observed ICP increase over 20
mmHg. The average value of transverse dislocation in these patients was 12 mm.
Conclusion: Increased intracranial pressure greater than 20 mm Hg in patients
with massive ischemic stroke can occur even when the oppression of the level of
consciousness to moderate coma and deeper on the background of the dislocation of
the brain. In case of an atrophy of the brain, the level of ICP may not exceed 20
mm Hg even with dislocation syndrome decompensation.
PMID- 26415296
TI - [MONITORING OF CEREBRAL OXYGENATION AND COGNITIVE FUNCTION IN CAROTID
ENDARTERECTOMY: THE ROLE OF TRANSIENT BYPASS OF CAROTID ARTERY].
AB - BACKGROUND AND OBJECTVE: Carotid endarterectomy (CEE) is an effective surgical
technique to prevent cerebral ischemia and stroke, but can be associated with
intervention-related complications. The surgical shunting of the intervention
area may reduce the risk of the intraoperative ipsilateral cerebral ischemia
following the carotid artery clamping but is controversial. The goal of this
study was to compare the cerebral tissue oxygen saturation (SctO2) and early
changes of cognitive functions in CEE in the settings of transient vascular
bypass and without this method. METHODS: 45 adult patients were randomized to
either the bypass group (the Bypass group, n = 24) or the Controls / No Bypass
(the Control group, n = 21). All patients were monitored for invasive arterial
pressure, SpO, EtCO,, and cerebral oxygenation (SctO2, Fore-Sight, CASMED, USA)
over the contra- and ipsilateral frontal head areas. The cognitive functions were
assessed using series of Montreal Cognitive Assessment score (MoCA) before the
intervention, and on 6 and 36 hrs after the CEE. RESULTS: We did not find
intergroup differences in the surgery duration, degree of stenosis and baseline
cognitive function. The values of SctO2 reduced significantly only above
contralateral side; these changes were attenuated in the shunt group. There were
no intergroup differences in postoperative cognitive function. CONCLUSION:
Empiric transient vascular bypass during carotid endarterectomy did not result in
significant changes of the ipsilateral cerebral oxygenation, hyperperfusion and
cognitive function, but attenuated the decrease of SctO2 over the contralateral
hemisphere.
PMID- 26415297
TI - [M1-OPIOID RECEPTOR AND CATECHOL-O-METILTRANSFERASE GENES POLYMORPHISM EFFECTS ON
PERIOPERATIVE PSYCHOLOGICAL CONDITION OF THE PATIENTS AND THE EFFECTIVENESS OF
POSTOPERATIVE ANALGESIA WITH OPIOIDS].
AB - OBJECTIVE: To evaluate the influence of ul-opioid receptor (OPRM1) 118A>G and
catechol-O-methyltransferase (COMT) 1947G>A gene single nucleotide polymorphisms
(SNP) combinations on postoperative opioid analgesia (POA) efficacy. MATERIAL AND
METHODS: In 100 consecutive patients scheduled for major urologic surgeries the
SNPs of OPRM1 118A>G and COMT 1947G>A (real-time PCR), preoperative anxiety and
depression level (HADS scale), POA efficacy ("Pain Out" questionnaire) have been
assessed. RESULTS: Preoperative anxiety and depression, additional analgesia
requirements, severity of nausea, drowsiness and incidence of vomiting were
higher in OPRM1 118G allele carriers. Maximum pain intensity and pain-related
restriction of mobility on first postoperative day were lower in homozygous
carriers of COMT 1947A. The best response to POA in view of preoperative anxiety,
analgesia efficacy and severity of nausea has been revealed in carriers of
combination COMT-OPRM1 AA-AA. CONCLUSIONS: SNPs of OPRM1 118A>G and COMT 1947G>A
affect the preoperative patients psychological status and POA efficacy.
PMID- 26415298
TI - [ORDER OF THE RUSSIAN FEDERAL SERVICE ON SURVEILLANCE IN HEALTHCARE].
PMID- 26415299
TI - [CRITERIA FOR THE QUALITY OF RESEARCH AND PUBLICATIONS IN MODERN
ANAESTHESIOLOGY].
PMID- 26415300
TI - [EXPERIENCE OF TRAINING AT THE ANESTHESIOLOGY DEPARTMENT OF THE SECOND AFFILIATED
HOSPITAL OF HARBIN MEDICAL UNIVERSITY (HARBIN, CHINA)].
AB - The article deals with an experience of short term training at the
anaesthesiology department of the Second Affiliated Hospital of Harbin Medical
University The author (graduate student of the Sechenov First Moscow State
Medical University) describes a structure of the operating unit, techniques of
anaesthesia for thoracic surgery, and organization of training and clinical
practice of Anaesthesiologists in China.
PMID- 26415301
TI - [OPTIMIZATION OF PRECLINICAL TRAINING OF ANAESTHESIOLOGISTS BASED ON THE
FORMATION OF PATHOGENIC SIMULATION LEARNING ENVIRONMENTS].
AB - Simulation training has become an important component of the postgraduate
training of anaesthesiologists for several reasons: organizational difficulties
in obtaining primary professional skills in a clinical setting, the opportunity
to study in a hospital existing pathology only and not planned in accordance with
the curriculum. This increases the risk of medical malpractice of young
specialist and study may be accompanied by complications and increasing the cost
of treatment. In our work, we have studied the factors of continuity of
preclinical and clinical stages of anaesthesiologists training in inhalation
anaesthesia based on the use of modern simulation technologies. We compared the
training programs and the results of traditional and simulation techniques,
defined the concept of quasi physiology and propedeutics of robots and
simulators, the role of clinical scenarios and reliability of robots of 6th level
of realism in the formation of pathogenic environment for simulation training. In
formulating the concept of pathogenetic simulation environment, we evaluated its
impact on the motivation of the trainees of studied category. The study included
23 interns, divided approximately in half into 2 groups, the 1st of which at the
preclinical stage of training was trained at the real operating theater gradually
studying the technique of inhalation anaesthesia with an experienced curator The
2nd group studied the same anaesthesia in clinical scenarios of a simulator robot
in a simulation operating theater Other components of the curriculum in the
groups did not differ. According to the results of pre-clinical training interns
started prforming an anaesthesia their self under the control of supervisor (i.e.
to the clinical stage). In the 1st group, a supervisor made the verdict of
readiness for clinical stage, and in the 2nd trainees were tested by the
performing a robotic anaesthesia maintaining targeted qualitative and
quantitative parameters. The evaluation was conducted according to the quality
and stability criteria of five consecutive "independent" anaesthesia, where the
highest scores were 100 points, confered by a supervisor. We found that for
interns' admission to the clinical stage in the 1st group, it took significantly
more educational anaesthesia than in 2nd group. It was also indirectly proved
expectedly greater regularity and predictability of anesthesia simulation
workshops. Based on the example of the clinical scenario of inhalation anesthesia
we showed a possibility of formation of pathogenic simulation environment without
excessive dramatization of studing environment, while maintaining the motivation
of trainees. Thus, simulation training is more efficient than traditional
schemes, in terms of providing the rational use of robotic systems of 6th level
of realism.
PMID- 26415302
TI - [EPIDURAL ANALGESIA FOR INTRAOPERATIVE AND POSTOPERATIVE CARE IN NEWBORNS].
AB - Anesthesia care in newborns has to be complex, balanced and safe. Nowadays
epidural analgesia (EA) in neonates during intra- and postoperative period is
widely used in Russia. Modern EA techniques imply the installation of a catheter
into epidural space at lumbar or thoracic level as well as different approach to
local anesthetics dosage. Newborns have special anatomy, physiology and
pharmacodynamics which have to be taken in mind when EA is used. At the present
moment Ropivacine (2 mg/ml) is approved for peripheral nerve blocks in newborns.
PMID- 26415303
TI - [INTRATHECAL OPIOID ANALGESIA - STATE IN THE WORLD AND IN THE RUSSIAN
FEDERATION].
AB - Intrathecal opioid analgesia has been used in clinic practice since 1979 and has
gained a great popularity till now due to its high analgesic potency
Unfortunately it is impossible to use opioids intrathecally in Russian Federation
by law because of nowadays official limitations. Russian national
anaesthesiologic society should comprehend benefits and side effects of this
method and make a decision if it is worth fighting for.
PMID- 26415304
TI - [Congratulations to Prof. Nedashkovsky].
PMID- 26415305
TI - [Congratulations to Prof. Yevdokimov].
PMID- 26415306
TI - [In memory of Professor Victor Mizikov].
PMID- 26415307
TI - DRAWING SKILLS IN CHILDREN WITH NEURODEVELOPMENTAL DELAY AGED 2-5 YEARS.
AB - In typically developing children, drawing development occurs in stages from
uncontrolled strokes to complex drawing. In this study, we examined drawing
development in children with neurodevelopmental delay (NDD). In order to do so,
we observed the influence of age, intraventricular hemorrhage (IVH) and gender on
the development of drawing skills. The sample consisted of 52 children with NDD,
aged 2 years and 6 months to 5 years. All children were hospitalized for
multidisciplinary team monitoring and developmental support. The evaluation of
drawing development was administered by giving each child a blank A4 paper and
the instruction to draw anything they wanted. All of the drawings were scored
satisfactory or unsatisfactory. Descriptive statistics was employed on all
relevant data to show results in frequencies and percentages. In order to
determine differences between groups, the chi2-test was administered. The results
showed greatest difference in drawing in children aged from 3 years to 3 years
and 11 months. Children with lower IVH had better drawing scores than children
with higher IVH levels. According to gender dissimilarities, a difference was
found showing girls to have better drawing skills than boys. All study results
pointed to the importance of early rehabilitation and continuous structured work
with children with NDD.
PMID- 26415308
TI - MICROBIAL PROFILE AND ANTIBIOTIC SUSCEPTIBILITY PATTERNS OF PATHOGENS CAUSING
VENTILATOR- ASSOCIATED PNEUMONIA AT INTENSIVE CARE UNIT, SESTRE MILOSRDNICE
UNIVERSITY HOSPITAL CENTER, ZAGREB, CROATIA.
AB - Ventilator-associated pneumonia (VAP) is very common in many intensive care
Units, but there are still many uncertainties about VAP, especially about the
choice of initial empiric antibiotics. The incidence of specific pathogens with
different susceptibility patterns causing VAP varies from hospital to hospital.
This is the reason why empiric initial antibiotic treatment for VAP should be
based not only on general guidelines (that recommend therapy according to the
presence of risk factors for multidrug-resistant bacteria), but also on up-to
date information on local epidemiology. The aim of this study was to determine
the microbial profile of pathogens causing VAP and their antibiotic
susceptibility patterns. The study was conducted in the 15-bed surgical and
neurosurgical Intensive Care Unit, Department of Anesthesiology and Intensive
Care, Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
Retrospective data were collected from September 2009 to March 2013. All patients
that developed VAP during the study period were eligible for the study. According
to study results, the incidence of VAP was 29.4%. The most commonly isolated
bacterium was Staphylococcus aureus (21.1%), followed by Pseudomonas aeruginosa
(19.0%) and Acinetobacter species (13.6%). All Staphylococcus aureus isolates
were susceptible to vancomycin and linezolid. Pseudomonas aeruginosa showed 100%
susceptibility to cefepime and very high susceptibility to pip'eracillin
tazobactam (96%), ceftazidime (93%) and ciprofloxacin (89%). Ampicillin-sulbactam
was highly effective for Acinetobacter species, showing resistance in only 8% of
isolates. In conclusion, according to study data, appropriate empiric antibiotic
therapy for patients with VAP without risk factors for multidrug-resistant
bacteria is ceftriaxone and for patients with risk factors for multidrug
resistant bacteria ampicillin-sulbactam plus cefepime plus vancomycin or
linezolid.
PMID- 26415309
TI - ULTRASOUND GUIDED FOAM SCLEROTHERAPY - THE SIMPLEST, LEAST INVASIVE, AND CHEAPEST
METHOD FOR VARICOSE VEIN TREATMENT.
AB - The aim is to present our experience and observations regarding varicose vein
treatment by means of ultrasound guided foam sclerotherapy (UGFS). The study
included 81 patients, 54 with insufficient main stem superficial veins in one
limb and 27 with both limbs affected. Great saphenous vein insufficiency was
diagnosed in 68, small saphenous insufficiency in 18, anterior accessory
saphenous vein insufficiency in 11, and Giacomini vein insufficiency in 3 limbs.
Seven limbs had combined insufficiency of great saphenous vein and small
saphenous vein, and 1 limb had combined insufficiency of Giacomini vein and small
saphenous vein. UGFS was employed to treat main stem vein reflux and their
tributaries. Within a month after treatment, all main stem veins were occluded
and only small corrections were performed occasionally to treat residual varices.
Regarding side effects, skin darkening and hard lumps at the sites of varicose
veins were most commonly observed. We also recorded several episodes of
thrombophlebitis. Few patients experienced dry cough, visual disturbances and
headache following the treatment. After six months, repeat UGFS of main stem
veins had to be performed in few patients. Very few patients expressed
dissatisfaction a year after treatment, mainly because of residual skin
darkening. In conclusion, UGFS proved to be the simplest, quickest and cheapest
method of varicose vein treatment. According to our experience, it yielded
satisfactory functional and cosmetic results. Side effects do occur, but are
acceptable, in particular at long term.
PMID- 26415310
TI - CORRELATION BETWEEN MAMMOGRAPHY DETECTED BREAST ARTERIAL CALCIFICATIONS AND
LIFESTYLE RISK FACTORS.
AB - The aim of the study was to investigate the association between some lifestyle
attributable risk factors of atherosclerosis, such as body mass index (BMI), oral
contraceptives, hormone replacement therapy, smoking and alcohol consumption with
breast arterial calcification (BAC) and its intensity on mammograms, and to
assess the impact of these lifestyle risk factors on mammography findings of BAC.
This prospective study included 300 women aged 47-69, i.e. a group of 149 women
with BAC on mammograms and control group of 151 women without BAC. Self-reported
BMI, use of oral contraceptives, hormone replacement therapy, smoking and alcohol
consumption were recorded by medical interview. The presence of BAC and its
intensity on mammography was compared according to the presence of high BMI and
use of hormone therapy, smoking and alcohol consumption. The results showed the
highest proportion of smokers (28.9%) in the group with mild BAC as compared with
the groups without calcification (14.6%) and with intense calcification (12.1%).
Women taking oral contraceptives had a higher level of calcified breast arteries
but no significant between-group difference was found for high BMI, hormone
therapy and alcohol consumption. Thus, study results showed the mammographic
finding of BAC to be inadequate to identify women with some lifestyle
attributable risk factors such as BMI, hormone replacement therapy, smoking and
alcohol consumption.
PMID- 26415311
TI - PSEUDOBULBAR AFFECT IN MULTIPLE SCLEROSIS PATIENTS.
AB - The aim of the study was to determine the prevalence of pseudobulbar affect (PBA)
in patients with multiple sclerosis (MS) and to analyze the link between PBA and
patient age, sex, clinical course of MS, disease duration and degree of
disability. The study was conducted on 79 MS patients that underwent inpatient
rehabilitation at the Lipik Special Hospital for Medical Rehabilitation in the
period from August 15, 2014 to February 15, 2015. PBA is a term used for an
emotional disinhibition syndrome characterized by sudden and involuntary episodes
of crying or laughing which are not in proportion to the stimulus applied or
occur without stimulus. The condition can be present in patients with various
neurological disorders, such as amyotrophic lateral sclerosis, Alzheimer's
disease, Parkinson's disease, patients having recovered from stroke, or following
traumatic brain injury. The estimated prevalence in patients with MS ranges from
10% to 46.2%. As a measuring instrument in the study, we used the Center for
Neurologic Study-Lability Scale (CNS-LS), where a sum 17 denoted positive
finding. The total number of respondents was 79, of which 33 (41.8%) met the CNS
LS criteria for the diagnosis of PBA. There was no statistically significant
correlation between PBA, age and degree of disability, although PBA was more
common in women and in patients with a secondary progressive form of the disease.
We found that 42.4% of respondents with positive CNS-LS criteria for PBA did not
inform their neurologist on the presence of sudden mood changes. The high
frequency of PBA and the fact that a significant proportion of patients did not
inform the neurologist on their affective disturbances call for an active
approach to diagnosis and treatment.
PMID- 26415312
TI - BMP-7 PROTEIN EXPRESSION IS DOWNREGULATED IN HUMAN DIABETIC NEPHROPATHY.
AB - Bone morphogenetic protein-7 (BMP-7) is expressed in all parts of the normal
kidney parenchyma, being highest in the epithelium of proximal tubules. It
protects kidney against acute and chronic injury, inflammation and fibrosis.
Diabetic nephropathy is the leading cause of chronic kidney disease, and is
characterized by decreased expression of BMP-7. The aim of our study was to
analyze whether the expression of BMP-7 is significantly changed in advanced
stages of human diabetic nephropathy. Immunohistochemical analysis of the
expression of BMP-7 was performed on archival material of 30 patients that
underwent renal biopsy and had confirmed diagnosis of diabetic nephropathy.
Results showed that BMP-7 was differently expressed in the cytoplasm of
epithelial cells of proximal tubules and podocytes among all stages of diabetic
nephropathy. At early stages of diabetic nephropathy, BMP-7 was strongly positive
in proximal tubules and podocytes, while low expression was recorded in the
majority of samples at advanced stages. In conclusion, increased expression of
BMP-7 at initial stages of diabetic nephropathy with subsequent decrease at
advanced stage highlights the role of BMP-7 in the protection of kidney structure
and function. Further investigations should be focused on disturbances of BMP-7
receptors and signaling pathways in patients with diabetic nephropathy.
PMID- 26415313
TI - IMPROVEMENT OF COGNITIVE EFFICIENCY THROUGH COGNITIVE TRAINING IN HEALTHY
SUBJECTS.
AB - The aim of the study was to explore whether application of cognitive stimulation
in young healthy subjects may improve their cognitive efficiency. The study
included 12 healthy young subjects divided into two groups, experimental group
and control group. Prior to cognitive stimulation treatment, both groups
underwent baseline measurements with selected neuropsychological tests. The
groups were matched with regard to the achievement on the baseline test. Only the
experimental group underwent daily application of different computer-based
cognitive tasks lasting for an hour a day for two weeks. After the treatment,
both groups were tested with the same neuropsychological battery used at the
baseline measurement. The experimental group showed a statistically significant
difference between the measurements on the variables assessing immediate
retention of visual material and recognition of verbal material. In addition,
qualitative analysis showed that the experimental group also had better
performance on the variables assessing delayed recall of visual material, visual
and verbal range of attention, and delayed recall of verbal material. In
conclusion, two-week cognitive stimulation in healthy subjects improves cognitive
performance, expressed as higher average values of certain neuropsychological
variables.
PMID- 26415314
TI - PERIORAL DERMATITIS: STILL A THERAPEUTIC CHALLENGE.
AB - Perioral dermatitis is a common and often chronic dermatosis. In its classic
form, it primarily affects women aged 15 to 45 years, but there are also variants
including lupus-like and granulomatous perioral dermatitis, where granulomatous
form is more common in childhood and affects mostly prepubescent boys. The
etiopathogenesis of the disease remains unclear, but there is a frequent finding
of prolonged use of topical products, especially corticosteroids, in the
treatment of rosacea and seborrheic dermatitis, preceding the clinical
manifestation of perioral dermatitis. Other causes important for the occurrence
of the disease include various skin irritants, as well as other physical and
hormonal factors, which all share the epidermal barrier dysfunction as an
underlying main pathogenic factor. Clinical presentation of papulovesicular
eruption in the perioral region with a typical narrow spared zone around the edge
of the lips is characteristic. Therapeutic approach should be individually
addressed, depending on the severity of clinical presentation and patient's age,
with special attention to patient's education and continuous psychological
support. In mild forms of perioral dermatitis, 'zero therapy' is the treatment of
choice. In the initial treatment period, patients with steroid-induced perioral
dermatitis should be closely followed up because the rebound phenomenon usually
develops after cessation of previous topical treatment. In moderate disease,
treatment includes topical metronidazole, erythromycin, and pimecrolimus, whereas
in more severe cases the best validated choice is oral tetracycline in a
subantimicrobial dose until complete remission is achieved. Systemic isotretinoin
should be considered as a therapeutic option for patients refractory to all
standard therapies.
PMID- 26415315
TI - THE RISK OF HYPERCOAGULABILITY IN OVARIAN HYPERSTIMULATION SYNDROME.
AB - Ovarian hyperstimulation syndrome (OHSS) is a rare and potentially life
threatening complication of infertility treatment occurring during either the
luteal phase or early pregnancy. An increasing number of thromboembolic
complications associated with the increased use of assisted reproductive
techniques have been reported in the literature. Identification of the risk
factors is crucial for prevention of thromboembolic events in OHSS patients.
Alterations in the hemostatic system cause hypercoagulability in women affected
by severe OHSS. Coexistence of inherited hypercoagulable conditions increases the
risk of thromboembolism. The role of clinical parameters that can help predict
development of thrombosis is controversial. Patients with a personal or family
history of thrombosis undergoing infertility treatment should be considered for
thrombophilia screening, while routine examination of inherited thrombophilic
mutations is not indicated in infertile patients. Antithrombotic primary
prevention is not indicated in healthy women undergoing assisted reproductive
procedures or in women with thrombophilia. Anticoagulant therapy is indicted if
there is clinical evidence of thrombosis or laboratory evidence of
hypercoagulability. In this review, the risks of hypercoagulability in the OHSS
are discussed.
PMID- 26415316
TI - PARTIAL TOPOGRAPHY-GUIDED PHOTOREFRACTIVE KERATECTOMY FOLLOWED BY CORNEAL CROSS
LINKING IN THE MANAGEMENT OF PROGRESSIVE KERATOCONUS: OUR INITIAL TEN-MONTH
RESULTS.
AB - The aim was to assess the results achieved in keratoconic corneas submitted to
the combined partial topography-guided photorefractive keratectomy (TG-PRK) and
corneal cross linking (CXL) procedure performed on the same day. Four patients
underwent this treatment of one eye. Corneal epithelium removal was performed by
50-micron phototherapeutic keratectomy. Then, partial TG-PRK laser treatment was
applied (Wavelight Allegretto, Eye Q, 400Hz), followed by corneal collagen cross
linking (CXL, 3 mW/cm2) for 30 minutes using 0.1% topical riboflavin solution.
Outcome measurements included uncorrected distance visual acuity (UCDVA), best
spectacle corrected distance visual acuity (BSCDVA), manifest refraction
spherical equivalent, keratometry, corneal high order aberration values, and
corneal tomography. At the end of 10-month follow up, all eyes showed improvement
in BSCDVA of 1-5 lines on Snellen chart. All other investigated parameters showed
significant improvement as well. One eye showed some topographic improvement, but
no improvement in UCDVA. No corneal haze, prolonged epithelial healing or
endothelial cell loss occurred. During 10-month follow up, the same-day combined
TG-PRK and CXL appeared to offer tomographic improvement and better visual acuity
in keratoconus patients.
PMID- 26415317
TI - MAJOR ANATOMIC VARIATIONS OF PULMONARY FISSURES AND LOBES ON POSTMORTEM
EXAMINATION.
AB - This study was aimed at determining major accessory fissures (MAF) and absence or
incompleteness of lobar or major fissures (MF) during routine forensic autopsies.
Prior to starting this prospective study, forms were prepared to collect data on
pulmonary lobes and fissures. In this study, 420 lungs of 210 autopsy cases were
examined for incompleteness and absence of MF and complete accessory fissures.
Horizontal fissures were incomplete in 18 right lungs. Incomplete oblique
fissures were noted in three right and two left lungs. Unidentified abnormal
fissures were determined in one left lung and five right lungs. The most common
fissural abnormality was less than half complete horizontal fissure. Four right
lungs had four lobes and two left lungs had three lobes because of complete
accessory fissures. The number of lobes in the left and right lungs and the
morphological features of both incomplete MF and MAF were determined in detail
and the variations were photographed. It is concluded that, in addition to
studies on computed tomography scans, autopsy series are useful for determining
the variations of MF and MAF of the lungs in different populations.
PMID- 26415318
TI - ADVERSE DRUG REACTIONS IN THE ORAL CAVITY.
AB - Every medication may lead to adverse effects, even when used in standard doses
and mode of application. In the oral cavity, adverse effects may affect every
part of oral mucosa and are the result of medications taken either locally or
systemically. Oral adverse reactions to drugs are not typical and therefore
sometimes not easy to recognize. On diagnosing adverse side effects in the oral
cavity, experienced clinician will usually diagnose the condition on the basis of
detailed medical history and clinical finding. However, the only objective
evidence for the offending drug is 're-challenge', i.e. exposure to the drug
after its discontinuation. It carries a huge risk of anaphylactic reaction;
therefore it has to be performed in a controlled hospital setting. Therapy is
based on immediate exclusion of the offending drug and, if lesions are present in
the oral cavity, topical or systemic corticosteroid therapy is prescribed. This
article gives a review of patients with oral adverse drug reactions referred to
the Department of Oral Medicine in Zagreb.
PMID- 26415319
TI - TIBIAL TUBERCLE AVULSION FRACTURE IN A MALE ADOLESCENT.
AB - Tibial tuberosity fractures are rare in childhood, most frequently due to
excessive quadriceps muscle contraction. On performing long jump, a 15-year-old
boy sustained tibial tuberosity avulsion fracture type II according to Watson
Jones. The patient was treated operatively with fragment repositioning and screw
fixation. Ten months after the injury and rehabilitation, he resumed his sports
activities with full range knee motion.
PMID- 26415320
TI - GIANT AGGRESSIVE ANGIOMYXOMA OF THE VULVA: CASE REPORT.
AB - A 57-year-old multiparous housewife was hospitalized at University Clinical
Center with painless, ulcerated, huge tumor of the vulva, which had progressively
increased in size during the last five years. It was a firm, ulcerated mass
involving the left vulva and measuring 35 cm in diameter. The vaginal orifice was
deviated to the right by the tumor. The adnexa and the uterus were normal. The
patient underwent total excision of the tumor in general anesthesia, and
histology confirmed aggressive angiomyxoma. She had an uneventful postoperative
period with satisfactory healing of the wound.
PMID- 26415321
TI - RENAL CELL CARCINOMA METASTASIS TO THE SINONASAL CAVITY: CASE REPORT.
AB - Renal cell carcinoma accounts for 3% of all adult malignant tumors. Common sites
of metastases are lungs, bone, liver, brain and adrenal glands. Metastatic
disease to the head and neck ranges from 15% to 30%. The 5-year survival rate
after nephrectomy is 60%-75%, but with multiorgan metastases the 5-year survival
rate is significantly lower, 0-7%. A case is presented of a female patient
diagnosed with renal cell carcinoma metastases to the paranasal sinuses,
diagnosed and treated at the Department of ENT and Head and Neck Surgery, Zadar
General Hospital, Zadar, Croatia. The tumor was surgically removed.
Unfortunately, the patient died one year after the procedure due to multiorgan
failure. Although metastases of renal cell carcinoma to the head and neck are
very rare, it should be first suspected when investigating a metastatic tumor in
this region. Surgical excision offers the best hope for long term survival. In
case of unresectable tumor, other treatment options should be considered such as
radiotherapy, immunotherapy and chemotherapy.
PMID- 26415322
TI - DYSPHONIA AS AN UNCOMMON PRESENTATION OF PONTOCEREBELLAR CHOROID PLEXUS
PAPILLOMA.
AB - A case is presented of a patient with dysphonia, hearing loss and ataxia due to
vestibulocochlear and vagal nerve compression by choroid plexus papilloma in the
cerebellopontine angle. Choroid plexus papillomas are rare tumors usually arising
in the lateral and fourth ventricle, and rarely found in the cerebellopontine
angle, making the neuroimaging characteristics usually not sufficient for
diagnosis. Patients usually present with headache and hydrocephalus but tumors in
the cerebellopontine angle can cause vestibulocochlear dysfunction and cerebellar
symptoms. Dysphonia along with hearing loss was a dominant symptom in the case
presented. After complete surgical removal of the tumor, deterioration of
dysphonia was noticed; it could be explained as peripheral vagal nerve neuropathy
due to tumor compression and intraoperative manipulation. In this case report, we
describe dysphonia as an uncommon presentation of a rare posterior fossa tumor.
To our knowledge, a case of choroid plexus papilloma presenting with dysphonia
has not been described before. Our case extends the differential diagnosis of
dysphonia from the otorhinolaryngological to the neurosurgical field.
PMID- 26415323
TI - COEXISTENCE OF ADDISON'S DISEASE AND PERNICIOUS ANEMIA: IS THE NEW CLASSIFICATION
OF AUTOIMMUNE POLYGLANDULAR SYNDROME APPROPRIATE?
AB - A case of autoimmune polyglandular syndrome (APS) is presented. A 45-year-old man
was admitted due to fatigue, malaise and inappetence. He had a history of primary
hypothyroidism and was on levothyroxine substitution therapy. One year before, he
was diagnosed with normocytic anemia and vitamin B12 deficiency, which was
treated with vitamin B12 substitution therapy. Physical examination revealed
hypotension and marked hyperpigmentation. Laboratory testing showed hyponatremia,
hyperkaliemia and severe normocytic anemia. Endocrinological evaluation disclosed
low morning cortisol and increased adrenocorticotropic hormone levels. Hence, the
diagnosis of Addison's disease was established. Additional laboratory workup
showed positive parietal cell antibodies. However, his vitamin B12 levels were
increased due to vitamin B12 supplementation therapy, which was initiated
earlier. Gastroscopy and histopathology of gastric mucosa confirmed atrophic
gastritis. Based on prior low serum vitamin B12 levels, positive parietal cell
antibodies and atrophic gastritis, the patient was diagnosed with pernicious
anemia. Hydrocortisone supplementation therapy was administered and titrated
according to urinary-free cortisol levels. Electrolyte disbalance and red blood
cell count were normalized. This case report demonstrates rather unique features
of pernicious anemia in a patient with Addison's disease. It also highlights the
link between type II and type III APS. Not only do they share the same
etiological factors, but also overlap in pathophysiological and clinical
characteristics. This case report favors older classification of APS, which
consolidates all endocrine and other organ-specific autoimmune diseases into one
category. This is important since it might help avoid pitfalls in the diagnosis
and treatment of patients with APS.
PMID- 26415324
TI - JAK INHIBITOR CLINICAL RESPONSE IN POLYARTHRITIS: CASE REPORT.
AB - The heterogeneity of rheumatoid arthritis (RA) presentation and molecular
signature of RA subclasses in patients with early changes of small peripheral
joints still remains a challenging problem. In clinical setting, classification
of the disease subtypes is not possible and treatment adjustment is based on the
continuous Disease Activity Score for disease severity recognition. A new
approach in the treatment appears with the novel non biologic targeted synthetic
disease-modifying antirheumatic drugs from the group of Janus kinase 1 and 3
(JAKI and JAK3), blocking interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21.
We report a case of a 48-year-old patient who had suffered from polyarthritis
from his age 40. Initial laboratory tests showed low inflammatory parameters and
magnetic resonance imaging of both hands indicated an early stage of RA.
Methylprednisolone and methotrexate therapy was initiated. The patient underwent
additional tests, but there was not sufficient evidence for a precise diagnosis.
According to the European League Against Rheumatism/American College of
Rheumatology score-based algorithm, the patient was classified as seronegative RA
based on joint involvement, duration of the disease, and synovitis not better
explained by another disease. A partial clinical effect of the administered
therapy (steroids as monotherapy and in combination, methotrexate and
leflunomide) was noticed with the use of systemic steroids, but dramatic
improvement was only achieved with a JAK inhibitor targeted therapy. Although the
use of anti TNF-alpha blocker is a proposed procedure and the drug has not yet
been registered in Europe, we took the opportunity to apply this new medication
option. The patient, a construction worker, was treated for 20 months, which led
to complete remission of the disease, without the need of basic or corticosteroid
therapy. Full functional capacity necessary in his demanding job was also
achieved. This result raised a question of timely introduction of
immunomodulators in the polyarthritis treatment steps.
PMID- 26415325
TI - INITIAL SYMPTOMATIC PITUITARY METASTASIS IN A PATIENT WITH PROSTATE FOAMY GLAND
CARCINOMA: TAILORING SAFE AND EFFECTIVE THERAPY.
AB - Metastases to pituitary gland are unusual and mostly asymptomatic, presenting
with local symptoms in one of ten patients, and only 3%-5% of them are of
prostate origin. Here we report and evaluate the effectiveness and safety of
multimodal treatment in a patient with pituitary metastasis of a prostate foamy
gland carcinoma. A 78-year-old male patient presented with blurred vision and
headache without a previous history of malignancy. Magnetic resonance imaging
scans revealed a large sellar mass, with infiltration of the surrounding
structures. Maximal transsphenoidal reduction of pituitary metastasis was
performed, with a histologic finding of metastatic prostate foamy gland
adenocarcinoma. Evaluation of the prostate specific antigen revealed a very high
level (1461 ng/mL) and foamy gland carcinoma was found on prostate needle biopsy.
The patient received 3D conformal external beam radiotherapy with 6 MV photons to
the sellar and parasellar region with a tumor dose of 44 Gy, followed by androgen
deprivation therapy. Follow up magnetic resonance imaging done after radiotherapy
showed shrinkage of the tumor process, with rapid prostate specific antigen
decline to 0.3 ng/mL. The visual function was fully established and headache
resolved. On the last follow up 14 months after the diagnosis, the patient was
alive and free from clinical signs of disease. Tailored treatment, including
limited radiotherapy in a higher palliative dose, in a patient with foamy gland
symptomatic pituitary metastatic disease resulted in good local and systemic
control of the disease. In older male patients with clinical and/or radiologic
characteristics suggestive of metastatic pituitary disease, the prostate specific
antigen test should be included as part of the work-up.
PMID- 26415326
TI - HISTORICAL REVIEW.
PMID- 26415327
TI - The Final Journey. .
PMID- 26415328
TI - Oral Care: When To Help, When To Encourage.
PMID- 26415329
TI - Cloud Computing: Implications For Providers.
PMID- 26415330
TI - 20 to Watch: Scaling New Heights--PART 2.
PMID- 26415331
TI - The Long and Winding Road--A New Editor's Perspective.
PMID- 26415332
TI - Effect of Luting Cement Space on the Strain Response of Gold Crowns Under Static
Compressive Loading.
AB - The aim the work was to investigate the effect of varying degrees of luting
cement thickness on the strain of the cemented gold alloy crowns under
compression. Five dies with their corresponding crowns were fabricated using a
lost wax technique. Three gold crowns for each die were fabricated under the
control of specific die spacer layers to provide a space of 40 um (10 layers of
die-spacer thickness) and 80 um (20 layers of die-spacer thickness). The crowns
were subsequently cemented using zinc phosphate cement. The crowns were subjected
to gradual static compressive loading between 10N to 250N (Newton) and the strain
measured simultaneously. The results were statistically analysed using
Independent t-test for the different die-spacer thickness at the 95% confidence
interval (p = 0.05). It was found that a significant relationship in the three
thicknesses. It was concluded that the absence of die-spacer significantly
reduced strain response, whereas a very little change in the strain recorded as
the die spacer layers has increased. Clinically, decreasing the number of die
spacer layers is advantageous as it provides a lower strain response under static
compressive loading that would improve the longevity of the cemented full crowns
inside the patient's mouth.
PMID- 26415333
TI - Hardness Changes of Tissue Conditioners in Various Storage Media: An in Vitro
Study.
AB - The aim of the present study was to evaluate the effects of storage media on the
longitudinal hardness changes of tissue conditioning materials. Four tissue
conditioning materials were used for fabrication of 80 disc-shaped specimens and
divided in four groups, stored in four storage media. The specimens underwent
artificial ageing corresponding to 30 nights of extra-oral storage. Hardness
measurements were obtained at nine intervals between 8 and 240 hours after
specimen fabrication. To test the effects of storage media on hardness we
employed multivariate modelling (Bonferroni correction; alpha = 0.05). The
materials exhibited varying hardness changes, most pronounced when stored in
ambient air.
PMID- 26415334
TI - An Investigation into the Accuracy of Two Currently Available Dental Impression
Materials in the Construction of Cobalt-Chromium Frameworks for Removable Partial
Dentures.
AB - This study investigated the suitability of irreversible hydrocolloid as an
impression material for cobalt-chromium framework construction. Scans of casts
derived from (1) alginate and (2) addition-cured polyvinylsiloxane impressions
were superposed on to a control. The differences within and between groups were
compared at fixed landmarks. The investigation revealed a high degree of scan
coincidence within and between groups. However, certain features, such as
undercuts, resulted in a lower degree of scan coincidence. Irreversible
hydrocolloid appears to be a viable alternative to addition-cured polyvinyl
siloxane as an impression material for cobalt-chromium framework construction.
PMID- 26415335
TI - The Influence of Sonic and Ultrasonic Vibration on the Shear Bond Strength of a
Selected Resin Luting Cement.
AB - PURPOSE: This study determined the effect of sonic and ultrasonic instrumentation
on the shear bond strengths of Panavia 21, a popular cement for the luting of
resin-bonded restorations. METHODS: 84 Ni-Cr cylinders were cemented to randomly
selected resin composite substrates using Panavia 21 following the manufacturer's
instructions. The Ni-Cr-composite specimens were divided into 7 groups of 12
specimens each based upon the procedure used for removing the excess cement. For
Group 1 (Co) specimens the excess cement was removed with microbrushes
immediately after cementation. Groups 2 through 7 were based on the use of
vibrating instrument and the time period after which the excess material was
removed. These included the cement, Panavia 21, three vibrating instruments,
Sonic with a universal tip (So), Piezoelectric ultrasonic with a USPIS tip (Pu),
Magnetorestrive ultrasonic with a FS1-100 tip (Mu) and two different time
periods, soon after cementation (9m) and one hour after cementation (1h). Once
excess cement REMOVAL WAS COMPLETED, THE SPECIMENS WERE SUBJECTED TO SHEAR
TESTING. RESULTS: Mean Shear Bond strengths ranged from 16.03 MPa (Co) to 19.91
MPa (So 1h). Statistical analysis demonstrated that interaction of the main
effects were significant (F = 4.27, p = 0.042). Post-hoc analysis demonstrated
that the effect of timing was significant in all the instrumented groups. The
majority of the tested specimens failed cohesively compared to mainly adhesive
failures for the control group. CONCLUSIONS: The effect of type of
instrumentation immediately following polymerization setting had no effect on the
shear bond strengths however a delay of 1 hour for all types of instrumentation
had a beneficial effect of improving observed shear bond strengths.
PMID- 26415336
TI - The Bond Strength of Resin Bonded Bridge Retainers to Abutments of Differing
Proportions of Enamel and Composite.
AB - Four groups of specimens were constructed using bovine enamel and composite
resin. After a period of ageing, the specimens were roughened and acid etched
before they were cemented to air abraded base metal alloy beams with a universal
resin cement. After further ageing, tensile peel testing was carried out using a
Universal Testing Machine. The force required to produce failure increased as the
amount of composite resin on the bonding surface of the abutment increased. This
difference reached statistical significance (p < 0.5) when the abutments
contained > 50% composite. The mode of failure was mixed on the majority of
retainers. Within the limitations of the study, findings suggest that RBB
retainers can be cemented to abutments restored with composite resin without a
reduction in bond strength.
PMID- 26415337
TI - The Windowed Removable Partial Denture: A Treatment Option for Patients with Lone
Standing Teeth.
AB - The decision as to whether to retain or extract a single remaining natural tooth
prior to the provision of dentures can be a difficult one. If the tooth is left
in situ, the development of an adequate peripheral seal around the denture is not
possible thereby compromising the appliance' retention. If the tooth is extracted
the possibility of gaining direct retention with the use of clasps or attachments
is lost. This paper aims to illustrate the use of windowed removable partial
denture design and review the literature relevant to this area. The use of such a
design can enhance the retention of the appliance by encircling the lone standing
tooth/teeth utilising an elastomeric permanent soft lining material.
PMID- 26415338
TI - Too Much To Swallow? A Case Report Of An Ingested Denture.
AB - Ingested foreign bodies can prove a significant and potentially fatal threat. A
case is reviewed where a patient swallowed his upper Kennedy Class I removable
partial denture, highlighting the potential problems of this prosthesis design
and the management of this scenario.
PMID- 26415339
TI - Prevalence of Gingivitis, Plaque accumulation and Decayed, Missing and Filled
Teeth among slum population in Bangladesh.
AB - A cross-sectional survey, using cluster sampling technique, of slum population,
was done to explore the oral health status and the prevalence of common oral
diseases. A close ended questionnaire comprising Decayed, Missing and Filled
Teeth (DMFT) Index, Gingival Index (Loe and Silness) and Plaque Index was applied
to evaluate and record oral diseases, in both male and female population,
covering a wide range of age groups. Clinical examination was carried out in
different shum set ups, including slum schools by trained and calibrated
examiners. Three thousand nine hundred and four (3904) slum dwellers participated
in the survey. Prevalence of Caries was expressed in mean DMFT, recording of
gingival status followed the method of Loe and Silness, oral hygiene status was
evaluated using Plaque index. Mean decayed component, of the DMFT, was
significantly higher than filling and missing component. Both decayed and missing
components showed increasing trend, and filling components decreased as the age
progressed. Prevalence of gingivitis and plaque accumulation was remarkably high
among slum dwellers. Significantly high level of common oral diseases was found
among Tongi slum dwellers.
PMID- 26415340
TI - Overt and subclinical hypothyroidism among Bangladeshi pregnant women and its
effect on fetomaternal outcome.
AB - OBJECTIVES: Thyroid disorders are among the common endocrine problems in pregnant
women. It is now well established that not only overt but subclinical thyroid
dysfunction also has adverse effects on maternal and fetal outcome. There are few
data from Bangladesh about the prevalence of thyroid dysfunction in pregnancy.
With this background, this study aims to find out thyroid dysfunction (both overt
and subclinical hypothyroidism) in pregnancy and its impact on obstetrical
outcome. METHODS: We studied the evaluation of 50 admitted pregnancies
corresponding to 29 women with subclinical hypothyroidism and rest 21 was overt
hypothyroidism. Detailed history and examination were performed. Apart from
routine obstetrical investigations, Thyroid Stimulating Hormone (TSH) estimation
was done. Their obstetrical and perinatal outcomes were noted. RESULTS: Overt
hypothyroidism was significantly (p < 0.05) higher in 25 to 44 years age group.
However two and three abortions were significantly (p < 0.05) higher in overt
hypothyroidism patients. In sub clinical hypothyroidism 86.2% conceived firstly
within 2 years and 66.7% in overt hypothyroidism patients conceived firstly in
between 3 to 5 years after marriage. Overt hypothyroids were prone to have
pregnancy-induced hypertension 42.9%, intrauterine growth restriction (P = 0.001)
and gestational diabetes (38.1%) as compared to subclinical cases. Neonatal
complications were significantly more in overt hypothyroidism group. Mean TSH
level was significantly (p < 0.05) higher in overt hypothyroidism patients but
mean FT4 level was almost similar in both groups. Majority of the patient
underwent caesarean section in both groups due to associated medical and
obstetrical complications. None of the babies showed hypothyroidism by cord blood
tests. In this analysis our results showed that overt hypothyroidism among
Bangladeshi pregnant women are associated with more maternal complication &
adverse parental outcome than subclinical hypothyroidism. The adequate treatment
of hypothyroidism during gestation minimizes risks and generally, makes it
possible for pregnancies to be carried to term without complications. Significant
adverse effects on maternal and fetal outcome were seen emphasizing the
importance of routine antenatal thyroid screening.
PMID- 26415341
TI - The Household Health Spending and Impoverishment: Findings from the Households
Survey in Shiraz, Iran.
AB - The present study aimed to investigate the households' impoverishment due to the
healthcare costs in Shiraz in 2012. In this household's survey, 800 households
were studied in Shiraz. The study sample was selected using stratified and
cluster sampling in the urban and rural areas, respectively. The information was
collected using the household section of the World Health Survey questionnaire.
In order to determine impoverishment due to health spending, at first, the
households' food-based poverty line (subsistence expenditure) was measured. Then,
households' health expenditure was subtracted from their total expenditure and if
the obtained value was lower than the households' food-based poverty line, the
households was considered to be impoverished due to health expenditures. The
collected data were entered into the SPSS (version 16) statistical software and
analyzed using descriptive statistic, Chi-square test, and logistic regression in
backward method. The study results showed that 7.1% of the households (CI: 0.071
+/- 0.018) were impoverished because of healthcare expenditures. Besides, the
households in the first quintile were more likely to be faced with poverty
compared to those in the other quintiles (p < 0.05). Being covered by health
insurance did not affect the protection from poverty due to health costs.
Moreover, the participants living in rural areas were faced with poverty more
than those living in urban areas (p < 0.05). It seems that health expenditure can
be an economic shock for household in Shiraz and through spending on health a
household may fall into poverty. As insurance had no effect on impoverishment, it
implies that change in health insurance plans and ways of health financing is
necessary.
PMID- 26415342
TI - Postoperative Perfluro-N-Octane tamponade for complex retinal detachment surgery.
AB - AIM: To study outcomes after using perfluoro-n-octane (PFO) as a short-term
postoperative vitreous substitute in eyes undergoing primary vitrectomy with or
without sclera buckling for complex rhegmatogenous retinal detachments with
inferior/multiple breaks or giant retinal tears (GRTs) or retinal detachment with
extensive proliferative vitreoretinopathy (PVR). METHODS: A prospective study was
carried out where in 43 patients (Group 1) PFO was exchanged with silicon oil in
the same surgical procedure and in 22 patients (Group 2) PFO was kept for 3 days
and then exchanged with silicon oil by a separate surgical procedure. The
respective surgeon took the decision whether to exchange PFO on the same day or
after 3 days. The patients were followed up for 6 months to analyze the
anatomical attachment rates, visual acuity gain, and postoperative complications
in both the groups. RESULTS: There were 33 male and 10 female patients in group 1
and 18 male and 4 female patients in group 2. Mean age distribution in group 1
was 38.88 years (SD +/- 21.45) and in group 2 was 38.09 years (SD +/- 16.36).
Mean preoperative best corrected visual acuity in group 1 was 2.02 +/- 0.58 and
in group 2 was 2.01 +/- 0.53 logarithm of the minimum angle of resolution
(LogMAR). The LogMAR Visual acuity in group 1 improved to 1.76 +/- 0.43 after 1
month (P = 0.01, paired t test) and to 1.62 +/- 0.62 after 6 months (P = 0.01,
paired T test). This visual acuity in group 2 improved to 1.85 +/- 0.42 after 1
month (P = 0.24, paired T test) and 1.90 +/- 0.72 after 6 months (P = 0.49,
paired T test). There was no difference regarding visual improvement in between
two groups after 1 month and 6 months of follow-up (P = 0.125, independent sample
T test). The retina was detached in 6 patients (14%) in group 1 and in 7 patients
(31%) in group 2 after 6 months of follow-up. There was no statistically
significant difference in between two groups regarding final attachment of retina
(P = 0.109, Fisher exact test). There was also no significant complication. like
increased posterior capsular opacification or glaucoma found after retaining PFO
for 3 days. Conclusion: Perfluoro-n-octane is efficacious and safe as a short
term vitreous substitute in primary rhegmatogenous retinal detachment repair
cases with inferior/multiple breaks or GRTs or with extensive PVR. But keeping
perfluoro-n-octane for 3 days does not significantly reduce the risk of re
detachment with complex rhegmatogenous retinal detachment cases.
PMID- 26415343
TI - Reference values of 6 minutes walk test (6 MWT) in Bangladeshi healthy subjects
aged 25-55 years.
AB - INTRODUCTION: The six minute walk test (6MWT) is increasingly accepted worldwide
to assess functional exercise capacity of cardiac and pulmonary diseases for its
simplicity. AIMS AND OBJECTIVES: The aim of the present study was to provide
reference values for 6 Minute Walk Distance (6MWD) and other primary variables
such as oxygen saturation (SaO2), pulse rate (PR) and breathlessness perception
done in 6MWT. METHODS: We studied a sample of 190 healthy subjects (53 females)
of age between 25-55 years (37.9 +/- 8.5 years). Baseline lung functions
including forced expiratory volume in 1st second (FEV1), forced vital capacity
(FVC) and FEV1/FVC ratio were measured by a flow sensing spirometer. All subjects
performed 6MWT according to standard protocol provided by the American Thoracic
Society (ATS) guidelines. The fatigue and dyspnoea was measured before and after
6MWT by modified Borg scale. The SaO2 and PR were measured also by a light weight
pulse oxymeter. RESULTS: The mean 6MWD was 466.7 +/- 69.4 meter, ranging from 213
to 659 meter and the mean Distance Work (DW) was 28732 +/- 7024 kg-m. Dyspnoea
status and oxygen saturation remained unaltered throughout the walk. Mean resting
and walking SaO2 values were, respectively, 97.1 +/- 1.3% and 96.8 +/- 1.5%: The
mean change in SaO2 was 3 +/- 1.5%. PR was significantly affected by the walk.
Mean resting and maximum PR after walking were respectively, 80 +/- 7 and 103 +/-
12 bpm (p < .01). Gender significantly affected the 6MWD (p < .01). In all
subjects, the 6MWD was inversely and directly related, respectively, to age (r =
.15; P < .05) and height (r = .41; P < .01). CONCLUSION: This study showed
reference values for the 6MWT variables of subjects in Bangladeshi population.
PMID- 26415344
TI - Association of Immunofluorescence pattern of Antinuclear Antibody with Specific
Autoantibodies in the Bangladeshi Population.
AB - Antinuclear antibody (ANA) is useful in the diagnosis of connective tissue
disorder (CTD). Association of specific autoantibodies with the
immunofluorescence pattern of ANA in CTD, noted in western literature has been
considered as reference in all over the world. However, in Bangladesh no such
research work or data correlating the autoantibodies and their ANA patterns is
found. Objective of the study was to identify an association between
immunofluorescence patterns of antinuclear antibody on HEp-2 cell and more
specific antinuclear reactivities (e.g. anti-dsDNA and anti-extractable nuclear
antigen) in the serum samples of CTD patients. Serum samples of 152 CTD patients
(Systemic lupus erythematosus, Rhumatoid arthritis, Sjogren's syndrome, Systemic
sclerosis, Polymyositis, Mixed connective tissue disease) were diagnosed
clinically, attending at Bangabandhu Sheikh Mujib Medical University (BSMMU)
during the study period of January, 2010 to December, 2010. Samples were
subjected for ANA testing by Indirect Immunofluorescence (IIF) on HEp-2 cell
(ALPHADIA) in dilution of 1:40, anti-dsDNA by ELISA and anti- extractable nuclear
antigen (anti-ENA) by Dot Immunoblot. Dot blot strips were tested for anti-Sm,
anti-RNP, anti-SSA/Ro, anti-SSB/La, anti-Scl-70 and anti-Jo-1. Out of 152
patients 110 (72.3%) cases were ANA positive by IIF on HEp-2 cell. ANA positive
sera exhibited four fluorescence patterns such as speckled (50.8%), peripheral
(21.6%) , homogenous (18.1%) and nucleolar pattern (9%). Peripheral pattern and
homogenous pattern was predominantly associated with anti-dsDNA (p < 0.05).
Speckled pattern was significantly associated with anti-ENA (p < 0.05).The most
commonly identified antinuclear autoreactivity was directed towards anti-RNP
(25.7%) then anti-Scl-70 (20%), anti-SSA (14.2%) and anti-SSB (5.7%). Multiple
anti-ENA reactivities were identified in 34.28% cases. Peripheral and homogenous
pattern is strongly associated with anti-dsDNA and speckled pattern may predict
anti-ENA (specially ribonucleoprotiens). As a definite correlation between the
ANA patterns and the group of antibodies was detected by dot immunoblot, one
could predict presence of certain specific auto antibodies for a particular ANA
pattern identified. This may restrict on the cost of laboratory investigations in
a developing country like Bangladesh. Thus, ANA-IIF method may reduce the expense
of detailed immunological work-up with minimal loss in diagnostic accuracy.
PMID- 26415345
TI - Study on oxidative stress and antioxidant level in patients of acute myocardial
infarction before and after regular treatment.
AB - In acute myocardial infarction (AMI), lack of oxygen delivery to myocardium leads
to generation of reactive oxygen species (ROS) which play an important role in
the pathogenesis of AMI. Endogenous anti-oxidants protect the myocardial tissues
from the deleterious effect of free radical mediate injury. The study evaluates
the extent of oxidative stress and antioxidant status against ROS in AMI patients
and amelioration of oxidative stress after regular treatment and also assesses
the association between oxidative stress and risk factors for atherosclerosis
like dyslipidemia and diabetes mellitus (DM). The study was conducted on 72 AMI
patients and age and sex matched 18 healthy controls. Patients were assigned to
four groups, AMI without dyslipidemia or DM, with dyslipidemia, with DM and with
both dyslipidemia and DM. Plasma malondialdehyde (MDA) and GSH content and
vitamin E levels were determined on admission into hospital and on the 5th day of
treatment. Plasma MDA level increased significantly (p < 0.001) and erythrocyte
GSH and plasma vitamin E levels were decreased (p < 0.001) in all the groups of
patients as compared to control. On the 50th day of regular treatment MDA level
reduced (p < 0.001) and GSH and vitamin E levels increased (p < 0.001) in
patients. The plasma MDA level was significantly higher (p < 0.001) in patients
with both dyslipidemia and DM or with only DM in comparison to patients without
dyslipidemia and DM. The difference in the GSH level between patients with risk
factors and without risk factors was not significant. It may be conclude that an
imbalance exists between oxidant and antioxidant molecules in AMI patients which
shift towards oxidative side and regular treatment restores this balance. There
may be some association between oxidative stress in AMI and risk factors like
dyslipidemia and diabetes mellitus.
PMID- 26415346
TI - Fingerprints: A simple method for Screening Hemophilic Patients.
AB - BACKGROUND: The present study aims to compare hemophilic patients' fingerprint
types with the normal people to help diagnose the disease, particularly new
occurrences of the disease. METHOD: This case-control study was conducted in
2012. Sixty two patients with hemophilia type A and 62 normal healthy people were
selected. The type of fingerprint was determined by a forensic specialist who was
kept unaware of the participants' group. Using advanced Henry method, the main
types of fingerprints were classified as arch, loop, whorl, as well as other
types. RESULTS: In the control group, loop type (65%) and in the case group the
whorl type (34%) were the most frequent fingerprint type (p < 0.001) and there
was a significant difference of fingerprint in each finger between two groups. In
addition, the average number of whorl type in the patients with mild disease was
significantly higher and the average number of arch and other types of
fingerprints was significantly lower than patients with moderate or severe
disease. CONCLUSION: The findings of the present study indicated that not only
are the fingerprints of normal and hemophilic people different, but also a
difference was observed between hemophilic patients with the mild factor level
and patients with moderate or severe one.
PMID- 26415347
TI - The Substance of De Spiritu.
AB - The aim of this paper is to depict the anatomical and physiological doctrines of
the treatise entitled Piepsilonrhoiota pinuepsilonupsilonMUalphatauomicronsigma,
or De spiritu. By closely examining the contents of the treatise on its own
accord, rather than through its Aristotelian or Hellenistic contexts, we attempt
to overcome the aporetic and often disconnected style of the author, and to
present a coherent picture of his doctrine of pneuma, its roles in the body, the
anatomical structures in which it acts, and its relation to the soul. We argue
that the author envisions three main systems in the body: arteriai, by which
external air is taken in, turned into pneuma and distributed to different parts
of the body; phlebes, by which blood is produced and distributed; bones and
neura, which support the body and effect locomotion. Pneuma is shown to run
through the system of arteriai, whereby it performs vital activities such as
thermoregulation, digestion and pulsation. It is also engaged in activities such
as perception and locomotion, in the form of the "connate pneuma," which, we
propose, is a component of bodily parts. The author connects pneuma very closely
with soul, and although he is familiar with Aristotle's doctrine of the soul, he
does not see to embrace it.
PMID- 26415348
TI - The Context of De Spiritu.
AB - This paper underlines the importance of the Pseudo-Aristotelian treatise De
spiritu for our knowledge of early Hellenistic anatomical and physiological
theories. We claim that the treatise verifies reports on certain 4th- and 3rd
century conceptions and debates otherwise attested only in later sources, and
offers invaluable information on otherwise unknown ideas and discussions. Our
claim is based on ten case-studies in which we explore the relation between the
views found in De spiritu and known to us from other ancient sources, regarding
ten specific topics. Following the results of our case-studies, we argue that De
spiritu should be dated to the early decades of the 3rd century BC, after the
circulation of the doctrines of Praxagoras of Cos, but before the discovery of
the central nervous system by Herophilus and Erasistratus.
PMID- 26415349
TI - Plato's Embryology.
AB - Embryology was a subject that inspired great cross-disciplinary discussion in
antiquity, and Plato's Timaeus made an important contribution to this discussion,
though Plato's precise views have remained a matter of controversy, especially
regarding three key questions pertaining to the generation and nature of the
seed: whether there is a female seed; what the nature of seed is; and whether the
seed contains a preformed human being. In this paper I argue that Plato's
positions on these three issues can be adequately determined, even if some other
aspects of his theory cannot. In particular, it is argued that (i) Plato
subscribes to the encephalo-myelogenic theory of seed, though he places
particular emphasis on the soul being the true seed; (ii) Plato is a two-seed
theorist, yet the female seed appears to make no contribution to reproduction;
and (iii) Plato cannot be an advocate of preformationism.
PMID- 26415350
TI - The Eclipse of the Sun: Sun-dials, Clocks and Natural Time in the Late
Seventeenth Century.
AB - The Sun, in the early seventeenth century was, as it always had been, the
ultimate arbiter of time-measurement In the last quarter of the century however
this role was called into question as the new precision of post-Huygenian clocks
revealed that natural time and the artificial mean time of the clock were not the
same. Initially the question was little understood by the general public. The
paper examines some early attempts to explain why "Sun-time" in 1700 was no
longer "true-time."
PMID- 26415351
TI - Roman vs. Arabic Computistics in Twelfth-Century England: A Newly Discovered
Source (Collatio Compoti Romani et Arabici).
AB - A frequently overlooked aspect of the knowledge transfer from Arabic into Latin
in the twelfth century is the introduction of the Islamo-Arabic calendar, which
confronted Western computists with a radically different scheme of lunar
reckoning that was in some ways superior to the 19-year lunar cycle of the Roman
Church. One of the earliest sources to properly discuss this new system and
compare it to the old one is the anonymous Collatio Compoti Romani et Arabici,
found in a manuscript from Tewkesbury Abbey, Gloucestershire. This article
contains the first edition and translation of this previously unknown text,
preceded by an analysis of its content and sources. As will be argued, the text
was written in the second quarter of the twelfth century as a reaction to the
astronomical tables of al-Khwaizmi, recently translated by Adelard of Bath, as
well as to eclipse observations that had exposed the flaws of the 'Roman'
computation.
PMID- 26415352
TI - On the Time of the Intellect: The Interpretation of De Anima 3.6 (43ob 7-20) in
Renaissance and Early Modern Italian Philosophy.
AB - This article argues that an original debate over the relationship between time
and the intellect took place in Northern Italy in the second half of the
sixteenth century, which was part of a broader reflection on the temporality of
human mental acts. While human intellectual activity was said to be 'above time'
during the Middle Ages, Renaissance scholars such as Marcantonio Genua (1491
1563), Giulio Castellani (1528-1586), Antonio Montecatini (1537-1599) and
Francesco Piccolomini (1520-1604), greatly influenced by the Simplician and
Alexandrist interpretations of Aristotle's works, proposed alterna- tive
conceptions based on the interpretation of De anima 3.6 (430b 7-20) according to
which intellectual acts happen in a both 'undivided' and 'divisible time'. In
order to explain Aristotle's puzzling claim, they were led to conceive of
intellectual activity as a process similar to sensation, corresponding to a
certain lapse of time (Castellani), an instant (Montecatini), or a mix of
instantaneousness and concrete duration (Piccolomini), depending on their
theoretical options.
PMID- 26415354
TI - Euclidization in the Almagestum parvum.
AB - The Almagestum parvum, a summary of Ptolemy's Almagest written around the year
1200, provided a new stylistic framework for the content of theAlmagest's first
six books. The author of the Almagestum parvum used a narrower range of types of
mathematical writing and supplied his work with principles, which were listed at
the beginning of each book and which were followed by propositions and
demonstrations. Specific values were to a large extent replaced by general
quantities, which would stand for a class of particulars. These and similar
changes in the Almagestum parvum reveal the author's concern with reshaping
astronomy into a discipline in the mold of Euclid's Elements, which emphasized
the generality of propositions and proofs and connected Ptolemaic astronomy to
the "mathematical toolbox" available in the Middle Ages. The Almagestum parvum
was an influential part of a larger trend of understanding Ptolemaic astronomy in
a non-Ptolemaic style.
PMID- 26415353
TI - Aristotle on Like-partedness and the Like-parted Bodies.
AB - This paper offers an interpretation of Aristotle's treatment of the homoeomerous,
or like-parted, bodies. I argue that they are liable to be far more complexly
structured than is commonly supposed. While Aristotelian homoeomers have no
intrinsic macrostructural properties, they are, in an important class of cases,
essentially marked by the presence and absence of microstructural ones. As I
show, these microstructural properties allow Aristotle to neatly demarcate the
non-elemental homoeomers from the elements. That demarcation, in turn, helps to
clarify Aristotle's conceptions of both homoeomery and what it is to be a bodily
element. On Aristotle's account, I argue, a homoeomerous body, as such, is
divisible into at least one part that is the same specific kind as the whole.
Elemental bodies are the limiting case. For Aristotle, an elemental body is only
divisible into parts that are of the same specific kind as the whole.
PMID- 26415356
TI - [CLINICAL CHARACTERISTICS OF T1 HIGH GRADE BLADDER CANCER].
AB - OBJECTIVES: We retrospectively evaluated characteristics of T1 high-grade bladder
cancer in patients in our hospitals. PATIENTS AND METHODS: Data was reviewed from
134 patients who were diagnosed with T1 high-grade bladder cancer and who
underwent transurethral resection (TUR) in our hospitals between January 2006 and
December 2012. The clinical course for each patient, the recurrence and
progression rates, and the risk factors for recurrence and progression were
evaluated. RESULTS: The median follow-up was 31.5 months. A second TUR was
performed in 55 patients (41.0%), and showed 32 cases of residual tumor (58.2%)
and 4 cases of upstaging (7.3%). The recurrence rate was 41.5%. The risk factors
for recurrence were (1) no muscle obtained in initial TUR, (2) no BCG, and (3) no
second TUR. The progression rate was 10.5%; no significant risk factors were
identified for progression. Within the T1 high-grade bladder cancer cohort, a
total of 31 patients underwent radical cystectomy (RC). When we graphed cancer
specific survival (CSS) curves stratified by pathological T stage at the time of
RC, and then compared findings from the upstage group (greater than pT2) and the
non-upstage group (less than pT2), the CSS rate was significantly higher in the
non-upstage group (p = 0.0027). CONCLUSION: No muscle in initial TUR, no BCG, and
no second TUR are factors associated with recurrence of T1 high-grade bladder
cancer. Further investigation is needed for preventing recurrence and progression
and for improving survival following radical cystectomy in T1 high-grade bladder
cancer.
PMID- 26415357
TI - [CLINICAL SURVEILLANCE OF PROSTATE CANCER--COMPARISON WITH CLINICAL MASS STUDY IN
JAPAN].
AB - OBJECTIVES: We report on the treatment trends and outcomes for prostate cancer in
our clinic retrospectively, and compared our data with the domestic clinical mass
study for prostate cancer. We then validated the legitimacy of our selected
therapy for prostate cancer. PATIENTS AND METHODS: Eight hundred and eighteen
patients at our clinic had histologically confirmed adenocarcinomas of the
prostate between January, 2000 and January, 2013. RESULTS: The age distribution
was from 47 to 100 years-old, with a median age of 72 years-old at diagnosis.
Clinical TNM staging indicated that 301 cases (36.8%) were stage I, 303 cases
(37.0%) were stage II, 101 cases (12.3%) were stage III and 113 cases (13.8%)
were stage IV. Three hundred and fifty two cases (43.0%) received some form of
androgen deprivation therapy (ADT). Retropubic prostatectomy (RPX) or radiation
therapy (RT), including external beam radiation therapy and brachytherapy, was
performed in 242 (29.6%) and 136 (16.6%) cases, respectively. The median overall
survival was 56.3 months and the respective cause specific 5 year and 10 year
survival rates of the 818 cases were 92.0% and 77.8%. Respectively, they were
100% and 100% for T1, 98.7% and 97.4% for T2, 90.7% and 38.5% for T3, and 60.8%
and 38.9% for T4. JUA (Japanese Urological Association) Cancer Registration
Statistics includes 11,385 eligible cases of prostate cancer, and had the same
distribution and the same therapy trends as our data base. NUORG (Nara Uro
oncological Research Group), the data base of 2,303 prostate cancer patients, and
our clinical study had the same distribution of D'Amico risk groups. Finally we
validated JCAP (Japan Study Group of Prostate Cancer) recommended J-CAPRA scores
in our prostate cancer patients who received primary androgen deprivation
therapies. Progression free survival and cause specific survival were related to
J-CAPRA scores. DISCUSSION/CONCLUSION: The Japanese prostate cancer patients have
higher prostate-specific antigen at diagnosis, higher Gleason score and higher
clinical stage than the US patients. The higher rate of primary androgen
deprivation therapy is characteristic for the Japanese patients.
PMID- 26415358
TI - [LAPAROSCOPIC ADRENALECTOMY: COMPARISON OF TRANSPERITONEAL AND RETROPERITONEAL
APPROACHES].
AB - OBJECTIVE: Laparoscopic adrenalectomy is generally performed by either a
transperitoneal approach (TA) or a retroperitoneal approach (RA). However, the
optimal selection criteria for each approach are unclear. We investigated the
factors affecting the safety of laparoscopic adrenalectomy to evaluate the
optimal criteria for each approach. PATIENTS AND METHODS: In total, 149 patients
who underwent laparoscopic adrenalectomy from February 1994 to July 2013 were
retrospectively analyzed. We performed TA for 75 tumors in 73 patients and RA for
78 tumors in 76 patients. Patient characteristics and operative outcomes were
compared between the two groups. Furthermore, operative outcomes in patients with
some surgical risks were specifically compared between the two approaches.
RESULTS: Patient characteristics were similar between the two groups, although
the patients in the RA group were significantly older than those in the TA group.
Four patients with a large pheochromocytoma in the TA group had excessive blood
loss and one of them was given blood transfusion. However, there was no
difference in intraoperative blood loss (p = 0.091). The other serious adverse
events were not observed. CONCLUSIONS: The present findings suggest that both RA
and TA can be effective surgical strategies, with close attention to large
pheochromocytoma to avoid excessive hemorrhage.
PMID- 26415359
TI - [ADRENAL HEMORRHAGE: 6 CASES AND A REVIEW OF 57 REPORTED CASES].
AB - PURPOSE: The guidelines on adrenal hemorrhage has not established in Japan. In
this article, we discuss the management of adrenal hemorrhage. OBJECTS AND
METHODS: We experienced 6 patients from November 2004 to September 2013 in The
University of Tokyo Hospital and The Fraternity Memorial Hospital, and we
searched 57 cases already reported in Japan by using Japan Medical Abstracts
Society (http://search.jamas.or.jp/). So we analyzed total 63 adrenal hemorrhage
cases in Japan. RESULTS: In 63 cases, 5 cases were performed TAE, 3 cases were
performed emergent surgeries, 13 cases were managed conservatively and elective
surgeries were performed in the other cases. 5 cases were fulfilled criteria for
Hb < 10 g/dl and the maximum diameter of the hematoma > 10 cm. Of 5 cases, 4
cases were performed emergent hemostasis. CONCLUSIONS: Adrenal hemorrhages caused
by metastatic tumor tend to be serious anemia. In addition, the most patients
with adrenal hemorrhages, who had Hb < 10 g/dl and the maximum diameter of the
hematoma > 10 cm, required immediate medical treatment, e.g. TAE or surgical
hemostasis.
PMID- 26415360
TI - [UNDIFFERENTIATED CARCINOMA OF THE URETER WITH FETAL CLINICAL COURSE: A CASE
REPORT].
AB - Undifferentiated carcinoma of ureter is rare neoplastic lesion, and the natural
history of undifferentiated carcinoma of ureter has not been known well yet. We
hereby presented an autopsy case of undifferentiated carcinoma of the ureter with
rapid progression from the initial stage. A 62-year-old male visited the local
urologist complaining of asymptomatic gross hematuria. Cystoscopy revealed the
outflow of hematuria from the right ureteral orifice. Abdominal CT showed the
right hydronephrosis with atrophic change of the renal parenchyma and the
stenosis of upper ureter. He was referred to our hospital on suspicion of a right
ureteral tumor. Magnetic resonance imaging and retrograde ureterography did not
reveal a tumor in the right ureter. He complained of low back pain 4 months after
the initial hematuria, and CT revealed the diffuse enlargement of the right
kidney, swelling of the abdominal lymph nodes, and lung nodules. Renal biopsy was
done, and only undifferentiated cells were revealed histopathologically without
any specific findings to diagnose the primary organ. The tumor increased
progressively, and he died about 6 months after the initial gross hematuria.
Autopsy was performed, and urothelial carcinoma was found in the right ureter as
the primary lesion. The ureteral tumor infiltrated to the right kidney, right
adrenal gland, liver, duodenum, and pancreas with undifferentiation.
Undifferentiated tumor cells were also found in distant metastatic lesion
including the abdominal lymph nodes, left adrenal gland, liver, lung, pleura, and
peritoneum.
PMID- 26415361
TI - [A CASE OF G-CSF PRODUCING SARCOMATOID CARCIONOMA OF URETER].
AB - We report a case of sarcomatoid carcinoma of the ureter in a 82-year-old woman.
She was admitted to our hospital with right hydronephrosis. A computed tomography
(CT) and retrograde pyelography (RP) showed a solid tumor at right ureter with
right hydronephrosis and 3 cm solid tumor on the right abdominal wall. She
underwent laparoscopic nephroureterectomy and excision of abdominal subcutaneous
tumor. Pathological diagnosis was urothelial carcinoma with sarcomatoid variant,
pT3, grade 3 and abdominal wall metastasis. Other metastasis occured in left
kidney and ileum about 1 month after the operation, and then she underwent
laparoscopic partial nephrectomy and ileocecal resection. The histopathological
diagnosis was sarcomatoid carcinoma with positive staining for granulocyte-colony
stimulating factor (G-CSF). The paient died of multiple metastases 5 months after
first operation. As far as we know, this is the first report of G-CSF producing
infiltrating sarcomatoid carcinoma of the ureter in Japanese paper.
PMID- 26415362
TI - [DISSEMINATED CARCINOMATOSIS OF THE BONE MARROW WITH UROTHELIAL CARCINOMA].
AB - Disseminated carcinomatosis of the bone marrow with urothelial carcinoma in a 75
year-old man: A case study. A 75-year-old-man had first medical examination due
to gross hematuria. The imaging study and cystoscopy revealed left ureteral and
bladder tumor. The patient was referred for a laparoscopic assisted left
nephroureterectomy and transurethral resection of a bladder tumor (TUR-Bt).
Pathological findings included urothelial carcinoma, high grade, both a pT3
ureteral tumor and a pTa bladder tumor. The patient received 2 courses of
gemcitabine and cisplatin and 1 course of methotrexate, epirubicin and nedaplatin
as adjuvant chemotherapy. TUR-Bt was performed twice due to recurrence in the
bladder and similar pathological findings. The patient received intravesical
instillation of pirarubicin (THP 30 mg in 30 mL of saline) to prevent recurrence
in the bladder, but discontinued in the 3rd time because of gross hematuria. The
patient was then admitted to our hospital due to gross hematuria, general
fatigue, and abnormal findings in the blood analysis. On admission, pancytopenia
was detected and the serum ALP level had increased to 30,266 IU/L. A biopsy and
bone marrow aspiration were performed because a super bone scan image was
obtained using a bone scintigram. Diffuse bone marrow metastasis of the
urothelial carcinoma was observed in the pathological evaluations. Therefore, our
diagnosis was urothelial carcinoma with disseminated carcinomatosis of the bone
marrow. Although treatment with zoledronic acid and blood transfusion were
performed, the patient died 20 days after the admission. To the best of our
knowledge, this is the first case of disseminated carcinomatosis of the bone
marrow with urothelial carcinoma.
PMID- 26415363
TI - [ANEURYSMAL TYPE RENAL ARTERIOVENOUS FISTULA WITH GIANT VENOUS ANEURYSM,
MIMICKING RENAL CELL CARCINOMA: A CASE REPORT].
AB - A 39-year-old man was referred to our clinic for a 7 cm tumor in the right
kidney, found by simple CT scan. It was suspected as renal cell carcinoma
accompanying tumor emboli in the inferior vena cava by enhanced CT scan. For
further evaluation of the tumor emboli, color Doppler ultrasound and enhanced MRI
was performed. They showed a large cystic lesion with high velocity turbulent
flow and flow voids in T2-weighted imaging, it seemed as giant venous aneurysm of
the right renal vein. Subsequently, angiography revealed aneurysmal type renal
arteriovenous fistula (AVF), transarterial embolization (TAE) of the arterial
feeder with coils was performed on the same day. After 6 months from
embolization, there was no recurrences or reinterventions. Color Doppler
ultrasound and MRI are beneficial in distinguishing vascular disease from
neoplastic disease which may sometimes mimick in other diagnostic imaging
studies. In addition TAE seems to be an effective treatment for the AVF.
PMID- 26415364
TI - [A CASE OF RIGHT PYONEPHROSIS DUE TO URETERAL STONES IN A HEMODIALYSIS PATIENT].
AB - We report a case of a 64-year-old male with right pyonephrosis due to ureteral
stones in association with chronic renal failure. The patient had been treated
with hemodialysis for fourteen years. He was admitted to the Department of
Internal Medicine of Kurobe City Hospital with chief complaints of fever and
lumbago in January 2013. CT demonstrated a right pyonephrosis accompanied by
right ureteral stones positioned in the middle and lower ureter. The stones could
not be detected by KUB. He was consequently referred to the Department of
Urology. Firstly, percutaneous nephrostomy for the right kidney was performed,
and 200 ml of pyuria was discharged at that time. Urine culture demonstrated
Escherichia coli. Secondly, rigid transurethral ureterolithotripsy (TUL) for the
right ureteral stones was performed using Lithoclast, and a ureteral stent was
indwelled on day 15 after nephrostomy construction. The nephrostomy catheter and
ureteral stent were removed 10 and 21 days after the operation, respectively. The
constituents of the stone were CaOx (26%) and CaP (74%). Right hydronephrosis
improved and the patient showed no pyelonephritis for 1 year postoperatively.
PMID- 26415365
TI - [MASSIVE HEMORRHAGE FROM THE FISTULA FORMATION BETWEEN CUTANEOUS URETEROSTOMY AND
INFERIOR EPIGASTRIC ARTERY: A CASE REPORT].
AB - A 87-year-old man received radical nephroureterectomy for right renal pelvic
cancer in 2009 and left cutaneous ureterostomy after radical cystectomy for
bladder cancer in 2013. He visited the hospital for exchanging a 7 or 8 Fr single
J catheter every 2 to 4 weeks. Eleven months after the 2nd operation, massive
bleeding from the stoma occurred when ureteral catheter was exchanged. Contrast
enhanced computed tomography showed that left inferior epigastric artery was
located close to left ureter. Angiography of the left inferior epigastric artery
didn't show an obvious fistula, but revealed the stoma was surrounded by ramified
new blood vessels from left inferior epigastric artery. We suspected a rupture of
the vessels and performed embolization for the branch of inferior epigastric
artery to left ureter. This embolization made it possible for the bleeding to be
controlled. Massive bleeding from the branch of inferior epigastric artery is
very rare, and we report the case and review the literature.
PMID- 26415366
TI - [SUCCESSFUL INGUINAL ORCHIECTOMY IN A PATIENT WITH A PAINFUL METASTATIC SPERMATIC
CORD TUMOR: A CASE REPORT].
AB - A 71-year-old man was referred to our department due to inflammation in the right
scrotum. A tumor in the right spermatic cord was suspected on palpation, and
abdominal computed tomography revealed a 4-cm mass in the tail of the pancreas
and a low-density lesion in the liver segment 6. In addition, the patient's serum
level of CA19-9 was high, at 135.7 U/mi. We referred the patient to our
institution's Department of Gastroenterology, where he was diagnosed as having a
liver metastasis from pancreatic cancer. Despite three courses of gemcitabine and
erlotinib combination therapy for pancreatic cancer, his serum level of CA19-9
increased to 744.0 U/m, indicating no response to chemotherapy. Because
uncontrollable pain developed in the right scrotum and right inguinal area during
the course of treatment, inguinal orchiectomy was performed for pain management
and pathological diagnosis. Careful examination revealed a hard, whitish tumor
occupying the right spermatic cord and extending from the epididymis to the
internal inguinal ring. Because a palpable mass in the peritoneum near the
internal inguinal ring was detected, part of the peritoneum was resected
concurrently. Pathological findings were remarkable with spermatic cord
metastasis and peritoneal dissemination from pancreatic cancer. Pain subsided
postoperatively and no analgesics were needed. Pancreatic cancer accompanied by
spermatic cord metastasis and peritoneal dissemination is extremely rare.
Surgical resection in the present case provided effective treatment of the
intractable pain due to spermatic cord metastasis. To the best of our knowledge,
this is only the 14th case reported in Japan of spermatic cord metastasis from
pancreatic cancer as a primary cancer.
PMID- 26415367
TI - NY-BR-1 Antigen Expression and anti-NY-BR-1 IgG in Egyptian Breast Cancer
Patients: Clinicopathological and Prognostic Significance.
AB - Breast cancer is the most common gynecological malignancy in the world. In Egypt,
it ranks the first among female malignancies with incidence of 37.7%. Over the
last decades, the integration of prognostic and predictive markers in treatment
decisions has led to more individualized and optimized therapy. NY-BR-1 antigen
has been shown to be frequently expressed in breast cancers. The study aimed to
assess the tissue expression of NY-BR-1 antigen and serum IgG antibody to this
antigen in Egyptian breast cancer females. The study was conducted on 60 females
(10 healthy, 10 having benign breast lesions, 40 with malignant breast cancer).
NY-BR-1 Ag expression was evaluated by immunohistochemistry and anti-NY-BR-1 IgG
was assessed by ELISA. Results revealed a significant difference in NY-BR-1 Ag
expression between benign and malignant breast cancer patients. There was a
significant correlation between NY-BR-1 antigen expression and estrogen
receptor's status (P = 0.019), stage of the disease (P = 0.008), menopausal
status (P = 0.008), lymph node involvement (P = 0.022) and anti-NY-BR-1 IgG (P =
0.032) among the studied individuals. In addition, there was a statistically
significant increase in anti-NY-BR-1 IgG O.D. results among malignant breast
cancer group. It is correlated with tumor type (P < 0.001) and progesterone
receptor status (P = 0.038). In conclusion, our work may represent a step towards
identification of a new prognostic marker specific for breast cancer.
PMID- 26415368
TI - Serum 25-hydroxyvitamin D and CD4+CD25(+high) FoxP3+ Regulatory T cell as
Predictors of Severity of Bronchial Asthma in Children.
AB - Bronchial asthma (BA) is one of the common chronic diseases of childhood. Vitamin
D deficiency has been associated with BA. Suppressor regulatory T cells (Treg)
are important for the induction, maintenance of immunological tolerance to
allergens. This study assessed serum 25-hydroxyvitamin D (vitamin D) and the
percentages of CD4+CD25+(high) Foxp3+ Treg, in peripheral blood, as predictors of
asthma severity and level of clinical control. The study enrolled 72 children
divided equally between asthmatic children (AC) and age and sex matched controls.
Diagnostic criteria and level of asthma severity followed the Global Initiative
for Asthma guidelines. Serum vitamin D was determined by an immunoassay and the
percentages of CD4+CD25+ig Foxp3+ Treg by flow cytometry. Serum vitamin D level
and percentage of CD4+CD25+(high) Treg were lower in AC compared to controls (P <
0.001) whereas Fox p3 expression was higher in AC compared to controls, P <
0.001. Serum vitamin D levels were lower in severe asthma compared to mild and
moderate forms (P = 0.008) and in uncontrolled attacks compared to partially or
completely controlled children. No difference in percentage of Treg in relation
to asthma severity and clinical control was observed. Since AC has decreased
serum vitamin D with inverse relationship between its levels and asthma severity,
we conclude that it can be used to predict severity of asthma.
PMID- 26415369
TI - Tumor Infiltrating T Lymphocytes and Apoptosis in Colorectal Cancer.
AB - Dysfunction of the immune system in colorectal cancer (CRC) can be due to a
number of reasons including apoptosis of tumour infiltrating lymphocytes (TILs).
The aims of this study was to investigate TILs in colorectal cancer and
characterize apoptosis of TILs using terminal deoxynucleotidyl transferase dUTP
nick end labeling (TUNEL) assay for detecting DNA fragments. We used monoclonal
antibodies (mAbs) to T lymphocytes to detect TILs and double immunohistochemistry
to assess apoptosis. T lymphocytes were detected in the immune infiltrate in CRC.
TUNEL staining disclosed a high level of cell death among TILs. Apoptosis of T
lymphocytes showed significant correlation with Dukes' stage (P = 0.02),
lymphatic metastasis (P = 0.03), vascular metastasis (P = 0.01), lymph node
metastasis (P = 0.02) and age of patient (P = 0.01). In conclusion, CRC may elude
immunological surveillance by inducing apoptosis of TILs.
PMID- 26415370
TI - Level of IL-16 and Reticulated Platelets Percentage during the Clinical Course of
Immune Thrombocytopenic Purpura in Children.
AB - Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease with
transient or persistent decrease of thrombocytes number in the blood. Cytokines
play important roles in the immune regulation and are known to be deregulated in
autoimmune diseases. This study aimed to investigate serum IL-16 levels in
relation to reticulated platelets in children with ITP and platelet count. Twenty
six children with ITP (11 with newly diagnosed ITP, 9 with persistent ITP and 6
with chronic ITP) and 12 age-matched healthy children controls were studied.
Serum level of IL-16 and reticulated platelets count were assessed by Enzyme
Linked Immunosorbent Assay (ELISA) and flow cytometry respectively. Serum IL-16
levels were significantly higher in patients as compared to controls (P < 0.001).
Within patients, the levels were higher in newly diagnosed compared to persistent
and chronic ITP (P < 0.01) and (P < 0.001) respectively. IL-16 levels were also
significantly higher in persistent ITP compared to chronic ITP (P < 0.001).
Reticulated platelets were also elevated in patients compared to controls and the
increase was significant in newly diagnosed group (P < 0.05). Negative
correlation was found between IL-16 level and reticulated platelets and platelets
counts (r = -0.284, P = 0.028, r = 0.274 P = 0.25) respectively. It is concluded
that IL-16 may be valuable in predicting the clinical course of pediatrics ITP.
Measurement of reticulated platelets may provide significant information about
thrombopoietic activity during the clinical course of ITP in children.
PMID- 26415371
TI - Serum Level of Growth Arrest-Specific 6 (Gas6) Protein and Genetic Variations in
the Gas6 Gene in Patients with Type 2 Diabetes Mellitus.
AB - Growth arrest-specific protein 6 (Gas6) belongs to a family of vitamin K
dependent coagulation proteins. Plasma levels of Gas6 are associated to altered
glucose tolerance. This study aimed at determining whether c.843+7G>A Gas6
polymorphism is associated with the development of type 2 diabetes mellitus. The
study included 50 patients with type 2 diabetes and 40 matched controls. The Gas6
protein was measured in serum using ELISA and Gas6 gene polymorphism by
polymerase chain reaction-Restriction Fragment Length Polymorphism. The GG
genotype was the most prevalent in the diabetic patient. The frequency of A
allele in the diabetic group was lower than the control group (P < 0.05). Serum
concentrations of Gas6 were lower among type 2 diabetes patients than controls (P
< 0.001). Since the AA genotype was expressed at a lower frequency in type2
diabetes patients compared to controls, a protective role for this Gas6 variant
in type 2 diabetic patients may be concluded.
PMID- 26415372
TI - Detection of Cytotoxic T-Lymphocyte Associated Antigen-4 Gene Polymorphism in
Type 1 Diabetes Mellitus.
AB - Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay
between genetic susceptibility and environmental factors is thought to provide
the fundamental element for the disease. It has been shown that more than 40
genetic loci are associated with T1DM. Important one among these is the CTLA-4.
This work aimed to detect Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4)
gene polymorphism in patients with type 1 diabetes mellitus T1DM using polymerase
chain reaction-restriction fragment length polymorphism (PCR-RFLP) to clarify its
role in the susceptibility to T1DM. The study was carried out on forty unrelated
Egyptian children with TIDM. Twenty unrelated healthy children were enrolled as a
control group. Blood samples were collected from patients and control groups and
subjected to CTLA-4 gene polymorphism analysis using polymerase chain reaction
followed by restriction fragment length polymorphism (PCR-RFLP). CTLA-4 G allele
and GG homozygous genotype were significantly increased in T1DM patients than in
control group (P < 0.001, P = 0.002 respectively). There was significant
association between the three CTLA-4 genotypes (AA, AG, GG) and diabetic
complications (p = 0.002), AG and GG polymorphisms were associated with
complications of diabetes with ratio 84.6% and 100% respectively. While no
association was found with sex, weight, height, risk factors of diabetes or
insulin treatment. It was concluded that there is a strong association between AG
polymorphism and T1DM (P = 0.002).
PMID- 26415373
TI - IL-17 Producing Cells and RORgammat mRNA Transcriptional Factor in Cirrhotic and
HCC Egyptian Patients.
AB - Retinoic acid-related orphan receptor gT (RORgammaT) is the orphan nuclear
receptor that regulates the development of Th17 cells and the expression of IL
17. The differentiation of Th17 cells is associated with the upregulation of
RORgammaT mRNA, and the mechanisms regulating that process in human cells are not
well understood. RORgammat as transcription factor was selectively expressed in
Th17 cells and is regulated by STAT3. The relationship between Th17 cells and
tumor immunopathology has been controversial. Aim of the study is to evaluate
Th17 cells and RORgammat transcriptional factor in cirrhotic, early and advanced
HCC patients. Ninety patients were studied (30 cirrhotic, 30 early stage and 30
advanced stage HCC patients). They were recruited from the National Liver
Institute, Menoufia University, and subjected to full clinical examination,
investigations to detect liver cirrhosis, portal vein thrombosis and tumor
staging. Peripheral blood mononuclear cells (PBMCs) were stimulated with cytosim,
ionomycin and monensin, and surface (CD4-PE)as well as intracellular staining for
Th17 (IL-17 FITC) was performed. Analysis of cells was carried out using FACS
Calibur. RORgammat mRNA expression in PBMCs was measured by real time RT- PCR.
Cirrhotic patients showed increased Th17% cells, without significant change in
RORgammat mRNA as compared to early stage HCC. Advanced stage HCC patients showed
significant increase of Th17 cells% and RORgammat mRNA compared to studied
patients group. Positive correlation of Th17 and RORgammatmRNA was found with
aminotransferases and bilirubin levels while, negative with serum albumin in
advanced stage patients group (P < 0.001). Both markers were significantly
increased with tumor size; RORgammat mRNA increased with multiple tumor foci. In
conclusion, Th17 cells and RORgammat may be useful prognostic markers for
advanced liver cirrhosis and HCC.
PMID- 26415374
TI - Prognostic Value of Serum Free Light Chain in Multiple Myeloma.
AB - The measurement of serum free light chain (sFLC) has been shown to be valuable in
screening for the presence of plasma cell dyscrasia as well as for baseline
prognosis in newly diagnosed patients. The aim of the present work was to study
the prognostic value of sFLC in multiple myeloma in relation to other serum
biomarkers, response to therapy and survival. Forty five newly diagnosed patients
with MM were included in the study. Patients were divided into responders and non
responders groups according to response to therapy. sFLC and serum Amyloid A
(SAA) were measured by immunonephelometry. The non-responders group showed a
statistically significant higher kappa/lambda or lambda/kappa ratio and higher
beta2 microglobulin level, but lower albumin level at presentation, as compared
to the responders group (P < 0.001). However, no statistically significant
difference was detected between the two groups regarding SA A or calcium levels.
Comparison between sFLC ratio obtained before and after therapy revealed
significant decrease after treatment in the responders group (P = 0.05). Survival
was significantly inferior in patients with an FLC ratio of >= 2.6 or <= 0.56
compared with those with an FLC ratio that was between 0.56 and 2.6 (P = 0.002).
PMID- 26415375
TI - Immunomodulatory Effects of Levofloxacin on Patients with Pneumonia in Assiut
University Hospitals.
AB - The immunomodulatory effects of antibiotics could influence the degree of
systemic and local responses to infection, so investigation of their intrinsic
influence on the host's inflammatory response appears to be essential.
Fluoroquinolones are known to exert modulatory activity on immune responses to
microbial infection. However the mechanism of this immunmodulation has not been
well elucidated. The aim of the work, is to assess the immunomodulatory effects
of a levofloxacin, through examining its effect on the concentrations of tumor
necrosis factor alpha (TNF-alpha) and Interleukin - 10 (IL-10) in serum of
pneumonic patients. After following local research ethics committee approval and
informed consent. This study included 40 patients with different types of
pneumonia, admitted to department of Chest Diseases, Faculty of Medicine, Assiut
University Hospitals, Egypt. Also, 10 healthy volunteers served as randomized
controls. Both patients and controls received levofloxacin (750 mg once daily for
10 days). Serum levels of TNF-alpha and IL-10 were measured in patients and
control before and after levofloxacin administration (750 mg once daily for 10
days) using human TNF-alpha and IL-10 ELISA kits respectively. Levofloxacin
caused a statistically significant decrease in the mean level of TNF-alpha in
both patients (20.82 +/- 1.31 pg/ml) (P < 0.009) and control group (17.12 +/-
0.84 pg/ml) (P < 0.004). In contrast, there was statistically significant
increase (P < 0.000) in the mean level of IL-1 0 in patients (61.75 +/- 2.85
pg/ml) while statistically significant decrease (P < 0.005) in control group
(28.57 +/- 1.37 pg/ml). In conclusion, our study demonstrates that treatment with
levofloxacin affects production of TNF-alpha as a pro-inflammatory cytokine and
IL-10 as an anti-inflammatory cytokines which may provide additional benefits in
treatment of respiratory tract infections that are independent of its
antibacterial properties.
PMID- 26415376
TI - [L-Lysine-alpha-Oxidase in vitro Activity in Experiments on Models of Viruses
Sindbis, Forest-Spring Encephalitis, Western Nile, Tyaginya and Dhori].
AB - The antitumor effect of L-lysine-alpha-oxidase from the culture fluid of
Trichoderma harzianum Rifai F-180 was investigated for the first time. The in
vitro studies revealed its high activity on a model of the forest-spring
encephalitis virus and no activity against the Sindbis, Western Nile, Tyaginya
and Dhori viruses.
PMID- 26415377
TI - [Estimation of Probiotic Lactobacilli Drug Resistance].
AB - An actual problem of analysis of probiotic lactobacilli resistance to antibiotics
and other drugs used in the treatment of gastro-intestinal disturbances has been
for the first time solved. The levels of resistance of 19 strains of
Lactobacillus (14 strains of L. fermentum, 4 strains of L.plantarum and 1 strain
of L.rhamnosus) isolated from commercial probiotics and sour milk products to 14
antibiotics of various nature, i.e. beta-lactams, aminoglycosides, macrolides,
clindamycin, vancomycin, rifampicin, ciprofloxacin, tetracycline and
chloramphenicol were determined. All the isolates were practically susceptible to
the drugs of the first line antihelicobacterial therapy, i.e. amoxicillin and
clarithromycin, that makes inexpedient the parallel use of the probiotics
containing the above lactobacilli in the treatment of gastritis and gastric
ulcer, despite the lactobacilli antagonism with respect to Helicobacter pylory.
Lactobacilli are as well resistant to mesalazin and can be used for correction of
dysbiosis in inflammatory affections of the intestine.
PMID- 26415378
TI - [Determination of Microbial Susceptibility to Sulfanilamides by Electrooptic
Analysis].
AB - The effect of sulfanilamides (soluble streptocid as an example) on changing of
the electrophysical properties (EP) of microbial cells of Escherichia coli XL-1,
BL-Ril, Pseudomonasputida C-11 and BA-11 was studied. It was shown that
significant changes in the orientation spectra (OS) of the cell suspensions
incubated at various concentrations of the sulfanilamide resulted in changing of
the electrooptic (EO) signal of the cell suspension at the first five frequencies
of the orientation electric field (10-1000 Hz) with the use of soluble streptocid
in a concentration of 0.3 mcg/ml. The dynamics of the drug effect on the
microbial cells demonstrated a decrease of the EO signal value 5 minutes after
the exposure by -59% vs. the control (the cells not exposed to the drug). During
the following exposure the EO signal value practically did not change (within
5%). The changes of the OS of the cell suspensions exposed to soluble streptocid
significantly differed for the susceptible and resistant strains. Determination
of the activity of sulfanilamides by electrooptic analysis of microbial cell
suspensions was considered possible. Changing of the microbial suspencion OS
under the effect of sulfanilamides can be used as a test on the microbial cell
susceptibility to drugs.
PMID- 26415379
TI - [Antibiotic Resistance of Microbial Isolates from Long-Term Healing Wounds
Exposed to Light of Various Wave Lengths].
AB - The data on inhibition of the growth of microorganisms of a characteristic
spectrum and antibiotic resistance isolated from long-term healing wounds by
light of various wave ranges are presented. The growing cultures on blood agar
were exposed to polarized light, red and infrared, ultraviolet of medium- and
short-wave continuous modes accustomed in physiotherapy of wounds.The effect of
light in some way induced inhibition of the growth, but complete recovery was
stated only after the use of ultraviolet light when confirmed quantitatively in
terms of the CFU.
PMID- 26415380
TI - [Kinetics of Virus Load HCV-RNA in Blood Serum and Peripheral Mononuclear Cells
in a Patient with Hepatocirrhosis and Chronic Virus Hepatitis C Termination
Treated According to Noninterferon Treatment Scheme (Cycloferon + Ribavirin)].
AB - A clinical case of hepatocirrhosis with chronic hepatitis C termination (1b
genotype) is described. Taking into account the cirrhotic stage of the disease,
the extrahepatic HCV replication in the peripheral mononuclears, unfavourable HCV
genotype, infavourable IL-28B gene polymorphism, inefficiency of the previous two
courses of the standard antiviral therapy (PegIFN + ribavirin) and secondary
immune deficiency, noninterferon antiviral therapy for 24 weeks was used in the
treatment of the patient: interferon-inductive therapy with cycloferon in
combination with ribavirin. There was observed by the 12th week of the treatment
biochemical remission and a significant decrease of the virus load from 1 x 10(7)
IU/ml to 7 x 10(5) IU/ml in the blood serum and from 1.35 x 10(7) IU/ml to 8 x
10(5) IU/m in the peripheral mononuclears. Investigation of the molecular
biological markers of the viremia (PCR HCV-RNA) in the cells of peripheral
mononuclears is an obligatory diagnostic technology in cases with suspected
extrahepatic HCV infection. The kinetics of the virus load and the positive
dynamics of the immunological indices in the patient at the cirrhotic stage of
chronic virus hepatitis C are indicative of the efficient etiopathogenic approach
with the use of the noninterferon treatment scheme (cycloferon + ribavirin), when
recombinant interferons are contraindicated.
PMID- 26415381
TI - [Brown Seaweeds as a Source of New Pharmaceutical Substances with Antibacterial
Action].
AB - At present the increase of antibiotic resistance in infection agents to
antimicrobial drugs requires discovery of new antimicrobial substances with
improved pharmacological properties and novel mechanisms of action, to which
microorganisms do not develop resistance. Three areas are of interest for the
search: recovery of new compounds from natural objects, including aquatic
organisms, chemical modification of the known antibiotic molecules, discovery of
compounds with antimicrobial activity among some new chemical structures which
have no analogues in nature. The review is mainly concerned with discussion of
antibacterial, antiviral and antifungal activity of sulfated polysaccharides
(fucoidans) and extracts of brown, red and green algae, as well as of
antioxidant, antiinflammatory, immunomodulatory and antiendotoxin properties that
contribute to their antiinfective action. Such an activity makes fucoidans
promising as a basis for developing new drugs for therapy of infectious diseases.
PMID- 26415383
TI - Stop DSM!
PMID- 26415382
TI - [ERCC1 as a Marker of Ovarian Cancer Resistance to Platinum Drugs].
AB - The review is concerned with the crucial marker of nucleotide excision repair
ERCC1 and its contribution to platinum resistance of ovarian cancer. All the
variants of the laboratory and clinical ERCC1 assessment in the ovarian cancer
tissue (single nucleotide polymorphisms of the ERCC1 gene, levels of mRNA or
protein) are considered. Data on the prognostic and predictive value of ERCC1 as
a marker of the response to platinum-based therapy in ovarian cancer are
systematized. The authors discuss the possible causes of heterogeneity of the
results and emphasize the necessity of a unified and integrated approach to
evaluation of ERCC1 in the tumor. The publications cited in the Search Engine Pub
Med up to January 2015 were analyzed.
PMID- 26415384
TI - Comparison of the Diagnostic Image Quality of the Canine Maxillary Dentoalveolar
Structures Obtained by Cone Beam Computed Tomography and 64-Multidetector Row
Computed Tomography.
AB - The objective of this blinded study was to validate the use of cone beam computed
tomography (C) for imaging of the canine maxillary dentoalveolar structures by
comparing its diagnostic image quality with that of 64-multidetector row CT
Sagittal slices of a tooth-bearing segment of the maxilla of a commercially
purchased dog skull embedded in methylmethacrylate were obtained along a line
parallel with the dental arch using a commercial histology diamond saw. The slice
of tooth-bearing bone that best depicted the dentoalveolar structures was chosen
and photographed. The maxillary segment was imaged with cone beam CT and 64
multidetector row CT. Four blinded evaluators compared the cone beam CT and 64
multidetector row CT images and image quality was scored as it related to the
anatomy of dentoalveolar structures. Trabecular bone, enamel, dentin, pulp
cavity, periodontal ligament space, and lamina dura were scored In addition, a
score depicting the evaluators overall impression of the image was recorded.
Images acquired with cone beam CT were found to be significantly superior in
image quality to images acquired with 64-multidetector row CT overall, and in all
scored categories. In our study setting cone beam CT was found to be a valid and
clinically superior imaging modality for the canine maxillary dentoalveolar
structures when compared to 64-multidetector row CT.
PMID- 26415385
TI - Oral Manifestations of Chronic Kidney Disease and Renal Secondary
Hyperparathyroidism: A Comparative Review.
AB - Recent epidemiological studies have demonstrated that significant associations
exist between oral disease and diseases involving non-oral tissues. Occasionally,
the roles may be reversed and the oral cavity can be severely affected by
systemic disease originating in another part of the body. Renal secondary
hyperparathyroidism is a common endocrinopathy that occurs as a consequence of
chronic azotemic kidney disease. Renal osteodystrophy, the most dramatic clinical
consequence of renal secondary hyperparathyroidism is uncommon, but can result in
demineralization of maxillofacial bones, loosening of teeth, and pathological jaw
fractures. The purpose of this report is to update the current understanding of
the pathophysiology of this endocrine disease and to compare the oral
manifestations of renal secondary hyperparathyroidism in humans and companion
animals. A 50-year review of the veterinary literature was undertaken to examine
the clinical presentation of renal osteodystrophy in dogs, and to determine what
clinical consequences of renal secondary hyperparathyroidism have been reported
in domestic cats.
PMID- 26415386
TI - The Negative Effects of Volatile Sulphur Compounds.
AB - Oral malodor has been studied extensively in humans but not necessarily to the
same degree in our veterinary patients where malodor constitutes a significant
problem. Breath malodor may originate from the mouth, or from an extra oral
source, originating from other organ systems such as gastrointestinal,
respiratory, or even systemic disease. Oral malodor is a result of microbial
metabolism of exogenous and endogenous proteinaceous substrates leading to the
production of compounds such as indole, skatole, tyramine, cadaverine,
puterescine, mercaptans, and sulphides. Volatile sulphur compounds have been
shown to be the main cause of oral malodor. Although most clients perceive oral
malodor to be primarily a cosmetic problem, there is an increasing volume of
evidence in human dental literature demonstrating that volatile sulphur compounds
produced by bacteria, even at low concentrations, are toxic to tissues and play a
role in the pathogenesis of periodontitis. This article reviews the current
available literature in human dentistry looking at these negative effects. No
veterinary studies have been conducted looking at the negative effects of
volatile sulphur compounds specifically, but as this article highlights, we
should be aware of the potential negative effects of volatile sulphur compounds
and consider this an area of future research.
PMID- 26415387
TI - Peripheral Giant Cell Granuloma in a Dog.
AB - Peripheral giant cell granuloma is considered rare in the dog with little known
about the clinicopathologic features. There are few reports in the veterinary
literature concerning this benign, reactive lesion, formerly known as giant cell
epulis. In humans, the four most commonly described reactive epulides are focal
fibrous hyperplasia (fibrous epulis), pyogenic granuloma, peripheral ossifying
fibroma, and peripheral giant cell granuloma. This case report describes the
diagnosis and surgical management of a peripheral giant cell granuloma in a dog.
PMID- 26415388
TI - Elodontoma in Two Guinea Pigs.
AB - Elodontoma was diagnosed in two pet guinea pigs, one involving a maxillary
premolar tooth and the other affecting a mandibular incisor tooth. Diagnostic
imaging, including radiographs, computed tomography, and oral endoscopy was
performed in order to quantify dental disease. Diagnostic imaging was also used
to guide treatment of acquired dental disease, which included intraoral
restoration of normal occlusal plane and tooth extraction using an extraoral
approach. These are the first histologically confirmed cases of elodontoma in
guinea pigs.
PMID- 26415389
TI - Maxillary Calcifying Epithelial Odontogenic Tumor in a Siberian Tiger (Panthera
tigris altaica).
PMID- 26415390
TI - Bilateral Rostral Mandibulectomy in the Dog.
PMID- 26415391
TI - [Regulation on Female-male Flower Ratio of Monoecious Plant Schisandra chinensis
Based on Reactive Oxygen Species (ROS)].
AB - OBJECTIVE: To study the effect of reactive oxygen species on female-male flower
ratio of Schisandra chinensis in order to improve the yield. METHODS: Spraying
different concentration solution of H2O2, paraquat and sodium dithionite on the
leaves of Schisandra chinensis before fruit bud initiation. RESULTS: Exogenous
sodium dithionite (O2- carrier) increased the female-male flower ratio greatly
from 7.6% to 42.3%. H2O2 and paraquat (OH- carrier) had little effect.
CONCLUSION: The regulation effects vary according to different ROS. Exogenous
sodium dithionite has the best effect.
PMID- 26415392
TI - [Effects of Pb Stress on Photosynthetic Pigment Biosynthesis and Growth of
Rabdosia rubescens].
AB - OBJECTIVE: To study the impacts of lead (Pb) stress on the leaf photosynthetic
pigment and the growth of Rabdosia rubescens,in order to provide a basis for
planting area selection and growth regulation. METHODS: Taking chlorophyll a,
chlorophyll b, carotenoids, growth rate, biomass and Pb content as the indexes,
the Ramets hydroponic experiments at Pb concentration levels (135,270 and 540
mg/L) in the time(20, 35 and 50 d) were carried out. Photosynthetic pigment
content was determined by spectrophotometer, and Pb mass fraction was detected
with plasma emission spectrometer. RESULTS: There was uncertain effect on
chlorophyll and carotenoid synthesis in different Pb concentrations in-early
period (20 and 35 d). At the time of 50 d, the chlorophyll content was higher in
the low-mid Pb concentrations, significantly lower in the high Pb concentration
compared with the control group, and there were no significant differences on
carotenoid contents in different Pb concentrations. CONCLUSION: Low-mid Pb
concentrations can promote chlorophyll synthesis, and the bioaccumulation of high
Pb concentration can inhibit the chlorophyll synthesis, and then restrict the
growth of Rabdosia rubescens.
PMID- 26415393
TI - [Relationship Between Seedling Grade of Glycyrrhiza uralensis and Plant Biomass
Accumulation, Yield and Quality of Product].
AB - OBJECTIVE: To research the relationship between the seedling grade of Glycyrrhiza
uralensis and the biomass accumulation, yield and quality of product, so as to
provide basis for establishing seedling standard. METHODS: The weight of single
seedling root was measured and the seedlings were divided into three grades by
the clustering analysis. The different grade treatments of seedlings were made to
conduct field trials and laboratory experiments. RESULTS: The weight of the whole
plant and dry root in growth period of grades 1 and 2 (the weight of single root
greater than 10.0 g) were larger than grade 3, and the yield was also the case.
The root of Glycyrrhiza uralensis, growing for three years, of grades 1 and 2
contained higher contents of active compounds than grade 3 and the content of
glycyrrhizin and liquiritin in the root of Glycyrrhiza uralensis of all
treatments were higher than the standard of Chinese Pharmacopoeia (2010 edition).
CONCLUSION: The plant from the grades 1 and 2 seedlings with larger growth
increment,higher output and better quality is the best seedling in cultivation.
PMID- 26415394
TI - [Study on High-yield Cultivation Measures for Arctii Fructus].
AB - OBJECTIVE: To find out the high yield cultivation measures for Arctii Fructus.
METHODS: Completely randomized block experiment design method was used in the
field planting, to analyze the effect of different cultivation way on agronomic
characters, phenological phase,quality and quantity of Arctii Fructus. RESULTS:
Arctium lappa planted on August 28 had the best results of plant height, thousand
seeds weight and yield. The highest yield of Arctii Fructus was got at the
density of 1,482 plants/667 m2. Arctiin content was in an increase trend with the
planting time delay and planting density increasing. The plant height, thousand
seeds weight, yield and arctiin content by split application of fertilizer were
significantly higher than that by one-time fertilization. Compared with open
field Arctium lappa, plant height, yield, arctiin content and relative water
content of plastic film mulching Arctium lappa was higher by 7.74%, 10.87%, 6.38%
and 24.20%, respectively. In the topping Arctium lappa, the yield was increased
by 11.09%, with 39. 89% less branching number. Early planting time and topping
shortened the growth cycle of Arctium lappa plant. CONCLUSION: The high-yield
cultivation measures of Arctii Fructus are: around August 28 to sowing, planting
density of 1 482 plants/667 m2, split application of fertilizer for four times,
covering film on surface of the soil and topping in bolting.
PMID- 26415395
TI - [Changes of Serum Gonadal Hormones Levels During Musk-secreting Period and Estrus
of Moschus berezovskii].
AB - OBJECTIVE: To detect concentrations of serum gonadal hormones (testosterone,
estradiol and progesterone) in musk-secreting period and estrus of Moschus
berezovskii, and to study the association of serum gonadal hormones
concentrations and musk-secreting. METHODS: The concentrations of serum gonadal
hormones were detected with magnetic particle separation ELISA. RESULTS: During
musk-secreting period, concentration changes of three serum gonadal hormones
showed clear regularity, three crests occurred synchronously. Before musk
secreting period, testosterone, estradiol and progesterone concentrations were at
its lower level, in prime musk-secreting period, they increased rapidly to
respective highest peak; at later musk-secreting period, they quickly dropped to
close to its previous levels before musk-secreting period. During estrus, serum
testosterone concentration increased to lower peaks than that at later musk
secreting period. Estradiol remained at a low level and progesterone level was
closed to zero. Serum testosterone concentrations in prime musk-secreting period
were 114.4 ~ 190.5 times of estrus. During musk-secreting period, there were
significant positive correlation among three serum gonadal hormone levels, a
positive correlation between musk yield and serum testosterone levels, and
negative correlation of musk yield with serum estradiol and progesterone levels
as well as musk deer ages. CONCLUSION: Serum testosterone concentrations in prime
musk-secreting period increase to the highest levels,which can provide reference
in musk secretion induced by artificial means.
PMID- 26415396
TI - [Determination of Five Active Components in Morinda officinalis from Different
Habitats by HPLC].
AB - OBJECTIVE: To establish a sensitive and specific high performance liquid
chromatography (HPLC) method for simultaneous determination of alizarin
anthraquinones (1-methoxy-2-hydroxy anthraquinone,1,2-dimethoxy-3-hydroxy
anthraquinone, rubiadin-1- methylether, 1,3-dihydroxy-2-methoxy anthraquinone,
rubiadin) in Morinda officinalis from different habitats. METHODS: The analysis
was carried out on an Ecosil C18 column (250 mm x 4.6 mm, 5 um) and detected with
an UV detector at the wavelength of 277 nm. Gradient elution was carried out with
acetonitrile-0.2% phosphoric acid at the flow rate of 0. 8 mL/min. The column
temperature was set at 30 degrees C. RESULTS: The calibration curves were linear
in the range of 0.2856-34.27 g/mL for 1-methoxy-2-hydroxy anthraquinone (r =
0.9999), 0.3268-39.22 g/mL for 1,2-dimethoxy-3-hydroxy anthraquinone (r =
0.9999), 0.3450-41.40 ug/mL for rubiadin-1- methylether (r = 0.9999), 0.1248-14.
98 ug/mL for 1,3-dihydroxy-2-methoxy anthraquinone (r = 0.9999) and 0.0508-6.096
ug/ mL for rubiadin (r = 0.9994), respectively. The average recoveries of the
five components were 99.4%, 100.2%, 101.4%, 97.2%, 103.2%, respectively. The
content of active components of samples from 10 different hatitats were in the
range of 0.0025-0.0722 mg/ g, 0.0016-0.0658 mg/g, 0.0022-0.0684 mg/g, 0.0182
0.3965 mg/g and 0. 0014-0.0179 mg/g. CONCLUSION: The established method is
accurate, reliable, and can be used for the simultaneous determination of the
five components in Morinda officinalis, which provides a scientific basis for the
quality evaluation of Morinda officinalis.
PMID- 26415397
TI - [Investigation Report of Tripterygium wilfordii and Tripterygium hypoglaucum].
AB - OBJECTIVE: To get the information of resources, cultivation, commodity
circulation and other aspects of Tripterygium wilfordii and Tripterygium
hypoglaucum. METHODS: Collect samples in 13 locations of Tripterygium wilfordii
and Tripterygium hypoglaucum, compare their plant morphological characteristics
and growth habit, and investigate their wild resources conditions, planting
information, easy-confused varieties and different commodity features. RESULTS:
(1) Tripterygium wilfordii and Tripterygium hypoglaucum were mainly collected
under woods or on the edge of woods,and light and moisture attributed to their
distribution to some extent. (2) Wild resources of Tripterygium wilfordii and
Tripterygium hypoglaucum were shrinking, and both of their cultivation history
were relatively short and their cultivation technique were still in a low level.
(3) Due to lack of harvesting and processing standards, decoction pieces, varying
from roots, rhizomes to stems of plants, were all sold as commercial medicines.
CONCLUSION: Wild resources of Tripterygium wilfordii and Tripterygium hypoglaucum
are shrinking,and the standardized research on cultivation-harvest processing and
commercial medicines remains to be further carried out.
PMID- 26415398
TI - [Preliminary Investigation of Medicinal Plant Resources in Kangle County, Gansu
Province].
AB - OBJECTIVE: To study the medicinal plant resources and their diversity in Kangle
County, Gansu Province, and to provide scientific basis on utilization and
protection of the medicinal plant resources of the county. METHODS: By field
survey, sample collection, taxonomic identification and data verification
methods. RESULTS: There were 258 species, 65 families in existing medicinal
plants, of which 43 species, 39 genera and 24 families were national protection
medicinal plants. Dominant families were mainly Asteraceae and Rosaceae. In this
area,the plants used whole herbs and roots ( or rhizomes) as medicinal materials
represented 40.31% and 25.19% respectively, and antipyretic and rheumatism
medicine accounted for 28.68% and 12.79% respectively. 12 medicinal plants were
cultivated and the cultivated area was 3,000 hectares. CONCLUSION: However, the
reserves of most medicinal plants are less enough and the resources are
diminishing increasingly in recent years. So we should accelerate the research
progress as well as developing and utilizing rationally on the premise of
protection.
PMID- 26415399
TI - [Influence on Strychni Semen's Analgesic Effect and Toxicity of Milk-Impregnated-
Processing-Technology of Traditional Uighur Medicine].
AB - OBJECTIVE: To investigate the effects of different processing methods on
analgesic effect and toxicity of Strychni Semen, and to provide the scientific
basis of milk-impregnated-processing-technology of traditional Uighur medicine
for toxic medicines. METHODS: Three different methods, frying with sand of
traditional Chinese medicine (1), cooled milk-impregnated-processing-technology
of traditional Uighur medicine (2), and heated milk-impregnated-processing
technology of traditional Uighur medicine (3) were used to process raw Strychni
Semen and the processed products were compared with those in the raw drug (4).
Karber method was used to caculate the LD50. RESULTS: The LD50 of (4), (1), (2)
and (3)were 273.0, 289.3, 289.3 and 339.2 mg/kg,successively. Low dose group of
heated milk-impregnated-processing-technology, low and high dose groups of cooled
milk-impregnated-processing-technology had significant inhibition on the acetic
acid-induced writhing reaction in mice (P < 0.05). CONCLUSION: Strychni Semen
processed by cooled and heated milk can enhance the analgesic effect in mice
while improving the LD50 of mouse, which illustrates milk-impregnated-processing-
technology's pharmacological mechanism on efficacy enhancing and toxicity
reducing of Strychni Semen.
PMID- 26415400
TI - [HPLC Fingerprint Study and Quantitative Determination of Index Components of
Pilea aquarum].
AB - OBJECTIVE: To establish an HPLC fingerprint and a quantitative determination
method for determination of index components of Pilea aquarum. METHODS: The HPLC
fingerprint of Pilea aquarum were determined on an Agilent Zorbax SB-C18 column
(250 mm x 4.6 mm, 5 um), eluted with mobile phase containing of acetonitrile-0.2%
acetic acid in a gradient mode. The temperature of column was 30 degrees C. The
flow rate was 0.8 mL/min and the detection wavelength was set at 330 nm. The
chromatograms of 24 batches of Pilea aquarum were compared by the software of
Similarity Evaluation System for Chromatographic Fingerprint of Traditional
Chinese Medicine (version 2004 A). The contents of luteoloside and cosmosiin were
also determined simultaneously. RESULTS: The HPLC fingerprint of Pilea aquarum
had been established. There were ten common peaks,two chromatographic peaks of
which were identified by reference substances. The samples of Pilea aquarum from
different habitats can be distinguished from their fingerprints, the contents of
luteoloside and cosmosiin varied greatly. CONCLUSION: This method has desirable
precision, stability, repeatability, and can be applied for identification and
quality control of Pilea aquarum.
PMID- 26415401
TI - [Material Composition Research on Tibetan Medicine "Brag-zhun"].
AB - OBJECTIVE: To study the material composition of Tibetan medicine "Brag-zhun", and
to provide the basis for interpretation of its source and reference for the
establishment of quality standards. METHODS: Pharmacognosy routine method was
used in macroscopic and microscopic identifications, inductively coupled plasma
spectrometry was carried out to determine 26 kinds of mineral elements,and X-ray
diffraction analysis was used for the crystalline phase detection of Brag-zhun.
The content of calcium,organic matter, humic acid and fulvic acid was determined
according to GB/T 14610-2008, "technical specification for soil analysis" , GB/T
11957-2001 and capacity titration, respectively. Moisture, ash content, acid
insoluble ash content and water soluble extract were determined with reference to
the Chinese Pharmacopoeia (2010 edition). RESULTS: Animal feces were commonly
found in Brag-zhun, the main crystal phase was SiO2, 26 kinds of mineral elements
content in total was about 3%, 13 batches of medicinal materials in organic
matter content was 29.03%-71.79%. Humic acid content was 28.37%-58.51%; fulvic
acid content was 19.69%-41.43%; moisture was 5.2% -11.7%; total ash content was
17.82%-64.39%; acid insoluble ash content was 2.10%-39.09%; and water soluble
extract was 28.39%-57.40%. CONCLUSION: The traditional record of Brag-zhun from
molten juice is lack of scientific basis. The mineral elements in Brag-zhun exist
in amorphous. Brag-zhun contains a lot of organic matter including humic acid and
fulvic acid, and inorganic matter mainly comes from sediment. The organic matter
in rock has gone through a long geological evolution.
PMID- 26415402
TI - [Study on Chemical Composition of Phyllanthus emblica].
AB - OBJECTIVE: To study the chemical constituents of Phyllanthus emblica. METHODS:
The chemical constituents were isolated and purified by silica gel, polyamide and
Sephadex LH-20 chromatography. Their structures were elucidated by
physicochemical proper- ties and spectral analysis. RESULTS: 13 compounds were
isolated and identified as Triacontanol (1), Triacontanoic acid (2), beta-Amyrin
ke- tone (3), Betulonic acid (4), Daucosterol (5), Lupeol acetate (6), beta
Amyrin-3-palmitate (7), Gallic acid (8), Betulinic acid (9), Ursolic acid (10),
Oleanolic acid (11), Quercetin (12) and Rutin (13). CONCLUSION: Compounds
1,2,4,6,7,9,10 and 11 are obtained from Phyllanthus emblica for the first time.
PMID- 26415403
TI - [Study on Chemical Constituents of Fermented Antrodia camphorata Powder].
AB - OBJECTIVE: To study the chemical constituents of fermented Antrodia camphorata
powder. METHODS: 15 compounds were isolated from Antrodia camphorata by Silica
gel column chromatography, ODS column chromatography, gel column chromatography,
preparative liquid phase chromatography separation technique, as well as
recrystallization. RESULTS: On the basis of their physical and chemical
properties and spectral data,their structures were identified as Ferulic acid
(1), Inositol (2), beta-Sitosterol (3),Vanillin (4),Vanillic acid (5), Butyric
acid (6), Daucosterol (7), p-Hydroxycinnamic acid (8), Lauric acid (9), Inosine
(10), Uridine (11), Adenine (12), D(+)-Sucrose (13), Arachidic acid (14) and
Guanosine (15). CONCLUSION: Compounds 1, 5, 6 and 8-15 are isolated from
fermented powder for the first time.
PMID- 26415404
TI - [Chemical Constituents from Cremastra appendiculata].
AB - OBJECTIVE: To study the chemical constituents of Cremastra appendiculata.
METHODS: The compounds were isolated by repeated column chromatography with
silica gel, Sephadex LH-20 and ODS-HPLC. The structures were elucidated by
analysis of spectroscopic data(1H-NMR and 13C-NMR). RESULTS: Ten compounds were
isolated from the EtOAc extract in the tuber of Cremastra appendiculata. Their
structures were identified as shancigusin I (I), 4-O-beta-D-glucopyranosyl
cinnamate (II), bulbocodin D (III), blestriarene A (IV), 7-hydroxy-2,4-dimethoxy
phenanthrene (V), coelonin (VI), militarine (VII), gastrodine (VIII), 3
hydroxyphenylpropionic acid (IX) and cinnamic acid (X). CONCLUSION: Compounds I
III, IX and X are isolated from Cremastra appendiculata for the first time.
PMID- 26415405
TI - [Study on Chemical Constituents of Peanut Hull].
AB - OBJECTIVE: To investigate the chemical constituents of peanut hull. METHODS:
Several chromatography methods such as silica gel and Sephadex LH-20 combined
with recrystallization were applied to isolate the compounds. Based on spectrum
technologies (MS,1H-NMR and 13C-NMR) and physico-chemical methods, structures of
isolated compounds were identified. RESULTS: Twelve compounds were isolated and
elucidated as luteolin (1), diosmetin (2), 5,7,3',4'-tetrahydroxy-8-prenyflavone
(3),5,7,3'-trihydroxy-4'- methoxy-8-prenylflavone(4), eriodicrtyol (5),
racemoflavone (6), hydnocarpin (7), 5,7-dihydroxy chromone (8), 5-hydroxy
chromone- 7-O-beta-D-glucoside (9), ferulic acid (10), beta-sitosterol (11) and
daucosterol(12). CONCLUSION: Except compounds 1, 5 and 8, all compounds are
obtained from peanut hull for the first time.
PMID- 26415406
TI - [Chemical Constituents from Leaves of "Chuju" Chrysanthemum morifolium and Their
Antioxidant Activities in vitro].
AB - OBJECTIVE: To study the chemical constituents from the leaves of "Chuju"
Chrysanthemum morifolium. METHODS: All compounds were separated and purified by
column chromatography over silica gel, Sephadex LH-20 and preparative HPLC. Their
structures were identified by spectral methods including 1H-NMR and 13C-NMR.
RESULTS: 21 compounds were isolated and identified as octa-cosyl alcohol (1),
beta-sitosterol (2), lupeol (3), alpha-amyrin (4), daucosterol (5),
ineupatorolide B (6), syringin (7), chlorogenic acid (8), petasiphenol (9),
physcion (10), acacetin (11), eupatilin (12), quercetin (13), diosmetin (14),
luteolin (15), apigenin (16), apigenin- 7-O-beta-D-glucopyranoside (17),
quercetin-3-O-beta-D-glucopyranoside (18), luteolin-7-O-beta-D-gluco pyranoside
(19), apigenin-7-O-beta-D- neospheroside (20), and acacetin-7-O-beta-D-glucoside
(21). CONCLUSION: Compounds 1-12, 18 and 20 are isolated from this plant for the
first time. Compounds 10, 13, 14, 15 and 16 have shown strong antioxidant
activities by DPPH . scavenging activity better than Vit C.
PMID- 26415407
TI - [Determination of Dencichine and Its Isomer in Panax notoginseng by Pre-column
Derivatization HPLC].
AB - OBJECTIVE: To establish a method to determine dencichine (beta-ODAP) and its
isomer (alpha-ODAP) in Panax notoginseng by pre-column derivatization HPLC with 1
fluoro-2,4-dinitrobenzene (FDNB). METHODS: A Luna-C18 column (250 mm x 4.6 mm, 5
um) was used, acetonitrile- (HAc-NaAc) as the mobile phase with the ratio of
17:83, the detection wavelength was 360 nm, the column temperature was 40
degrees C, and 20 uL of sample was injected for HPLC analysis. RESULTS: In 0.30
50.50 ug/mL,beta-ODAP had a good linear relationship with peak area, A2 =
140.50C1 + 72.30, r1 = 0.9995; In 0.10-16.15 ug/mL, alpha-ODAP has a good linear
relationship with peak area, A2 = 106.60C2 + 56.00, r2 = 0.9992. CONCLUSION:
There are appreciable beta-ODAP and alpha-ODAP in different samples of Panax
notoginseng. The method is simple, rapid, accurate and can be used for the
detection of dencichine and its isomer in other samples.
PMID- 26415408
TI - [Study on Chemical Constituents of Lonicera japonica Bud].
AB - OBJECTIVE: To study the chemical constituents of Lonicera japonica bud. METHODS:
The compounds were isolated and repeatedly purified by silica gel column
chromatography, gel column chromatography and ODS chromatography. The structures
were elucidated by physicochemical properties, MS and NMR. RESULTS: Eight
compounds were isolated and their structures were identified as protocatechuic
acid (1), 5-hydroxy-7,3',4'-trimethoxyflavone (2), hyperoside (3), 4
hydroxycinnamic acid (4), ethyl caffeate(5), apigenin (6), 5-hydroxy-6,7,8,4'
tetramethoxyflavone (7), and ethyl laurate (8). CONCLUSION: Compounds 5, 7 and 8
are obtained from this genus for the first time.
PMID- 26415409
TI - [Study on Chemical Constituents of Fat-soluble Extraction from Lepidium meyenii].
AB - OBJECTIVE: To study the chemical constituents of the fat-soluble extraction from
Lepidium meyenii root. METHODS: Different extraction methods were studied,
including supercritical carbon dioxide extraction, circumfluence extraction and
steam distillation. Chemical constituents of the fat-soluble extraction from
Lepidium meyenii were analyzed by GC/MS. RESULT: The number of compounds isolated
by the above four methods were 38, 31, 14, 21 (specific gravity less than 1 in
steam distillation) , and 25 (specific gravity greater than 1 in steam
distillation), accounting for 85.79%, 81.18%, 62.08%, 98.36% (specific gravity
less than 1 in steam distillation) and 81.54% (specific gravity greater than 1 in
steam distillation) of each total peak area, respectively. CONCLUSION: This study
lays a certain foundation for further study and development of functional factors
in Lepidium meyenii root.
PMID- 26415410
TI - [Volatile Oil Analysis of Piper hongkongense form Different Hatbitats by GC-MS].
AB - OBJECTIVE: To analyze the volatile oil in Piper hongkongense from five different
habitats. METHODS: The volatile oil was analyzed by GC-MS. RESULT: The volatile
components oil of each sample varied significantly. Caryophyllene, alpha
caryophyllene and nerolidol 2 were common constituents of five samples. The
volatile oil and chemical constituent contents of fresh sample were higher than
that of the old sample. CONCLUSION: The volatile oil and chemical constituent
contents of Piper hongkongense from different habitats have sig- nificant
differences, which are affected by habitats, harvest season, storage time and so
on.
PMID- 26415411
TI - [Simultaneous Determination of Three Components in Ficus microcarpa Leaves by
HPLC].
AB - OBJECTIVE: To develop an HPLC method for the content determination of benzoic
acid, 4-hydroxyphenylacetic acid and acetosyringonecas in Ficus microcarpa
Leaves. METHODS: The determination was performed on Purospher(r) STAR C18 (250 mm
x 4.6 mm,5 um). The mobile phase was consisted of acetonitrile-0.2% phosphoric
acid aqueous solution with linear gradient elution and the flow rate of 1.0
mL/min. The column temperature was set at 35 degrees C and the detection
wavelength was 270 nm. RESULTS: The linear range of benzoic acid, 4
hydroxyphenylacetic acid and acetosyringonecas was 0.0121-1.21 ug (r = 0.9995),
0.423-42.32 [Lg ( r = 0.9999) and 0.047-4.70 pg( r = 0. 9996) , respectively. The
average recovery was 100.7, 101.2 and 96.5 respectively. CONCLUSION: This method
is simple,reproducible,and can be used for determination of three components of
benzoic acid, 4-hydroxyphenylacetic acid and acetosyringonecas in Ficus
microcarpa Leaves.
PMID- 26415412
TI - [Effect of Madecassoside on Intestinal Mucosal Immunity in Collagen-Induced
Arthritis Rats].
AB - OBJECTIVE: To explore the changes of intestinal mucosal immunity in collagen
induced arthritis rats and the impact of madecassoside on these changes. METHODS:
Collagen-induced arthritis was established in female Wistar rats. Treatment group
was orally administrated madecassoside once daily for consecutive 21 days, while
blank control and model groups were orally administered saline at the same
volume. The concentrations of sIgA in small intestine content and IFN-gamma in
small intestinal tissue homogenate were determined by ELISA. The proportions of
CD4+ T and CD8+ T in the epithelium and laminar propria of small intestine were
detected by flow cytometry, and the ratios of CD4+/CD8+ were calculated. The
relative expressions of CD80, CD86, IL-6, IL-12 and Foxp3 mRNA in the small
intestine were determined by real-time PCR. RESULTS: Compared with blank control
rats, the concentrations of sIgA in small intestine content and IFN-gamma in
small intestinal tissue homogenate from model rats were increased, the ratios of
CD4+/CD8+ in the epithelium and laminar propria of small intestine were higher
and the relative expressions of CD80, CD86, IL-6 and IL-12 mRNA in the small
intestine were increased. Madecassoside treatment decreased the concentrations of
sIgA in small intestine content and IFN-gamma in small intestinal tissue,
downregulated the ratios of CD4+/CD8+ in the epithelium and laminar propria and
decreased the relative expressions of CD80, CD86, IL-6 and IL-12 mRNA, while
upregulated the relative expression of Foxp3 mRNA in the small intestine.
CONCLUSION: The intestinal mucosal immune response is enhanced in collagen
induced arthritis rats, the antigen presenting cells are activated abnormally and
the immune tolerance is disturbed. Madecassoside treatment can downregulate the
intestinal mucosal immune response and benefit for the induction and maintenance
of intestinal immune tolerance.
PMID- 26415413
TI - [Effect of Ju-Pi-Tang on Cisplatin-induced Emetic Model in Minks].
AB - OBJECTIVE: To study the antiemetic effect of Ju-Pi-Tang from Jin Kui Yao Lue on
cisplatin-induced emetic model in minks, and to observe the immunoexpression of
peripheral and central c-fos and substance P. METHODS: The minks were randomly
divided into blank control group, Ju-Pi-Tang blank control group, model group,
ondansetron group, aprepitant group, Ju-Pi-Tang (in high-, mid-, and low-dose)
groups. Every group was administered with the antiemetic agent or distilled water
on 24 h before cisplatin injection. The antiemetic effect of drugs was
investigated in the emetic model of minks induced by cisplatin in 72 h
observation. Immunohistochemistry was used to compare the differences of c-fos
and substance P expression in the area postrema of brain and distal ileum
tissues. RESULTS: During observation period,compared with model group,the
frequency cisplatin induced retching and vomiting was significantly reduced by Ju
Pi-Tang in high- and mid-dose groups, during the 0-24 h acute period, the number
of retching of Ju-Pi-Tang in high-dose group was decreased more than aprepitant
group, during the 24-72 h delayed period, the number of both retching and
vomiting was decreased more than ondansetron group, after 72 h of cisplatin
administration, compared with model group, the grey levels of c-fos and substance
P expression in distal ileum and brain tissues of Ju-Pi-Tang groups were higher
significantly. CONCLUSION: Ju-Pi-Tang has a good effect against cisplatin-induced
emesis in minks.
PMID- 26415414
TI - [Effect of Curcumin on Cerebral Ischemia-reperfusion Injury in Rats].
AB - OBJECTIVE: To investigate the effect of curcumin on cerebral ischemia-reperfusion
injury in rats and its mechanism. METHODS: 250 male SD rats were randomly divided
into five groups:sham group (Sham group), ischemia-reperfusion group (I/R group),
curcumin groups with dosage of 30 mg/kg (Cur30 group), 100 mg/kg (Cur100 group)
and 300 mg/kg (Cur300 group). The brain tissue damage degree, leukocyte cells
infiltration, levels of TNF-alpha and MMP-9 expressions, and blood-brain barrier
permeability were detected. RESULTS: At the same time point,the score of brain
tissue injury,number of leukocyte, expression of MMP-9 and TNF-alpha, and Evans
blue dye of I/R group and Curs group were higher than those of Sham group (P <
0.05). The score of brain tissue damage degree, number of leukocyte, expression
of MMP-9 and TNF-alpha, and Evans blue dye of Cur groups were lower than those of
I/R group (P < 0.05). The Cur100 group had the best effect. CONCLUSION: Curcumin
can decrease cerebral ischemia reperfusion pathological damage significantly and
suppressed the expression of MMP-9 and TNF-alpha, and Evans blue dye, brain
tissue damage, leukocyte infiltration, which may be involved in protective
mechanisms of curcumin.
PMID- 26415415
TI - [Protective Effect of Component Compatibility Sini Decoction on Hypothyroidism
Induced Renal Damage in Rats].
AB - OBJECTIVE: To investigate the protective effect of component compatibility Sini
Decoction on hypothyroidism induced renal damage in rats. METHODS: The
hypothyroidism model were established by 0.1% propylthiouracil (PTU) solution 10
m/kg for consecutive 15 days. Rats were randomly divided into model group,
component compatibility Sini Decoction groups[ CSD 9. 6,4. 8 and 2. 4 g/ (kg .
d)] and positive control group [Euthyrox 9 ug/(kg . d)]. Radioimmunoassay was
used to determine the serum T3 and T4 levels; serum BUN content was detected by
UV spectrophotometer and ELISA method were used to measure the CYS-C content. The
kidney was weighed, and the pathological changes of the renal were detected by HE
stain. RESULTS: Compared with blank control group, kidney weight coefficient,
serum T3 and T4 levels in model group were decreased, while serum BUN and CYS-C
contents were increased (P < 0.05 or P < 0.01). Compared with model group, serum
T3 and T4 contents were increased and serum BUN and CYS-C contents were decreased
(P < 0.05) in Sini Decoction groups [CSD 9.6 and 4.8 g/(kg . d)] and positive
control group. The HE stain results showed that component compatibility Sini
Decoction and Euthyrox could relieve glomerular atrophy and renal tubular
epithelial cell injury in rats. CONCLUSION: Component compatibility Sini
Decoction has a curative effect on hypothyroidism induced renal damage in rats.
PMID- 26415416
TI - [Study on Optimum Extraction Process of Water Soluble Protein from Coicis Semen].
AB - OBJECTIVE: To optimize the extraction process of water soluble protein from
Coicis Semen. METHODS: Coicis Semen was used to extract protein with cysteine
hydrochloride aqueous solution in alkaline environment. The single factor test
was conducted with the factors of extraction temperature, extraction pH, solid
liquid ratio and extraction time. In combination with single factor test results,
a 4 factors 3 levels orthogonal experiment was designed with the factors of
extraction temperature, extraction pH, solid-liquid ratio and extraction time.
The effect of various factors on the results and the interactions were analyzed
by range analysis, variance analysis and partial least squares regression
analysis. RESULTS: The optimum extraction process of water soluble protein from
Coicis Semen was as follows: the extraction temperature was 40 degrees C , the
extraction pH was 10, the solid-liquid ratio was 1:20 and the extraction time was
4 h. The interaction of temperature and solid-liquid ratio, as well as
temperature and extraction time would lower protein extraction rate. CONCLUSION:
The optimized extraction process is economical, simple, reasonable and
practicable.
PMID- 26415417
TI - [Optimization of Extraction Process of Total Flavonoids from Schizonepeta
tenuifolia Based on Analytical Hierarchy Process with Dose-Effect Comparison
Method].
AB - OBJECTIVE: To optimize conditions for extracting total flavonoids from
Schizonepeta tenuifolia by the method of analytical hierarchy process with the
correlation method of dose-effect. METHODS: Take the amount and concentration of
ethanol,the extraction time and times as examine factors, with the inhibition
rate of Caco-2 human cloning colonic cancer cell as index to optimize the optimum
conditions of total flavonoids from Schizonepeta tenuifolia by orthogonal
experiment design, and analyze the Pearson correlation coefficient between the
total flavonoids content, hesperidin content, extraction rate and
pharmacodynamics indexes through SPSS 19.0 software to determine the dose-effect
comparative indicators, and then analytic hierarchy process is adopted to define
the weight coefficients range of the content of total flavonoids and hesperidin.
RESULTS: The best extraction process conditions were as follows:15 times the
amount of 75% ethanol, water circumfluence extracting for 3 times,each time for 2
hours; The weight coefficient ranges of the content of total flavonoids and
hesperidin were 0.7500-0.9000 and 0.1000-0.2500 respectively. CONCLUSION: Using
the comprehensive scores of the content of total flavonoids and hesperidin, which
is calculated by weight coefficient ranges that based on the analytical hierarchy
process,to replace the inhibition rate as the indicator to optimize the optimum
extraction process is scientific and reasonable. This optimization process is
simple and practical,which provides a new method for selecting the best
extraction indicators to get effective ingredients from traditional Chinese
medicine.
PMID- 26415418
TI - [Study on Error Analysis of Nonlinear Function Coefficient of FAIMS].
AB - The solution of ion mobility's nonlinear function coefficients alpha2 and alpha4
is the basis for achieving substance identification of High Field Asymmetric
waveform Ion Mobility Spectrometry (FAIMS). Currently, nonlinear function
coefficients alpha2 and alpha4 lack priors, meanwhile, existed solving results
about alpha2 and alpha4 are deficient in error evaluation standard. In this
article, acetone, isopropanol and 1, 2-dichlorobenzene were detected under
different dispersion voltage by homemade FAIMS. In general, the spectrum peak of
same sample at different dispersion voltage value is unique. Different dispersion
voltage and corresponding compensation voltage value determines the value of
alpha2 and alpha4. According to sample spectra at different dispersion voltage
value, groups of spectral characteristics were obtained. Affirmatory number of
data which were selected from multiple sets of compensation voltage value and
dispersion voltage value, so that they were utilized to solved out lots of alpha2
and alpha4. Lots of factor have an effect on the accuracy of the solving results
of alpha2 and alpha4, for instance, value of compensation voltage and dispersion
voltage, style of fetching points of dispersion voltage, and so on. Comparing to
other factors, style and amount of dispersion voltage is likely to control. By
data analyzing huge amounts of alpha2 and alpha4 data, this paper explored their
characteristic of distribution and correlation about them, research influence of
number and method to fetch dispersion voltage detected points for error of
solving results. After fitting frequency of alpha2 and alpha4, it was found that
they conform to normal distribution, goodness of fitting exceed 0. 96, thus
standard deviation of their distribution are able to evaluate error of solving
results. In addition, a strong correlation exists between them, relevance of
sample is -0. 977, -0. 968, -0. 992 respectively. With increasing of computing
selected points, the corresponding error of solving results decrease. By
comparing the standard deviation of method to fetch dispersion voltage detected
points, found that detecting frequency in case of detecting maximum and the 70%
of maximum of dispersion voltage value is lower at approximately same standard
deviation, solving effect was optimized in unique fetching points style. Based on
the premise of ensuring the accuracy of solving results of alpha2 and alpha4, it
is obvious that reducing the frequency of detections for FAIMS effectively. It
created favorable conditions for rapid field detection and precise spectral
analysis.
PMID- 26415419
TI - [Research Progress on Laser-Induced Breakdown Spectroscopy Based on Resonance
Excitation].
AB - Laser-induced breakdown spectroscopy (LIBS), a new kind of atomic spectrum
analysis technology, has attracted much atterition of the researchers due to its
characteristics of real-time, simultaneous multi-element analysis, and no sample
preparation. However, the poor analytical sensitivity has been an important
factor that restricts the development of this technology. LIBS based on resonance
excitation combines atomic fluorescence spectroscopy and laser-induced breakdown
spectroscopy and selectively excites the target elements. In this way, the
analytical sensitivity of LIBS can be improved substantially and its application
for trace elements detection is greatly expanded. In this paper, the research
development of LIBS based on resonance excitation is summarized. The generation
of atomic, fluorescence spectrum in laser-induced plasma, the typical
classification and the basic principle of LIBS based on resonance. excitation are
introduced. The influence of ablation laser energy, resonant laser energy and
wavelength, delay between the ablation laser and the resonant laser, and the gate
width on spectral enhancement are analyzed in detail. The application status and
deficiencies of LIBS based on resonance excitation in the fields of metallurgy,
environmental monitoring and isotope detection are elaborated. Future prospects
of LIBS based on resonance excitation are also described.
PMID- 26415420
TI - [Radiative Properties of Cirrus Clouds Based on Hexagonal and Spherical Ice
Crystals Models].
AB - Single scattering properties for spherical and hexagonal ice crystal models with
different size parameters and wavelengths were employed to calculate satellite
observed radiation and downward flux in ground surface using RSTAR radiative
transfer model. Results indicated that simulated satellite observed radiation and
ground surface downward radiant flux from different shapes of ice crystal models
were different. The difference in the spectral radiation fluxes between 0. 4 and
1. 0 um was largest, and particle shapes affected the downward radiant flux
significantly. It was verified that the proper selection of the effective ice
crystal model is not only important for retrieval of the microphysical and
optical parameters of the cirrus cloud, but also important for obtaining the
radiant flux on the earth's surface correctly. These results are important for
retrieving cloud microphysical parameters and simulation of the ground surface
downward radiant flux.
PMID- 26415421
TI - [Study of PL Spectra of PbSe Quantum Dots for IC Chip Temperature Dependence].
AB - Colloidal PbSe QDs were prepared with the particle size of 3. 6, 5. 1 and 6. 0
nm, and the temperature-dependent optical properties of colloidal PbSe QDs were
investigated. At the room temperature, the experiment showed that there is red
shift with increasing temperature; photoluminescence spectra of large size
colloidal PbSe QDs is blue shifted with increasing temperature. Proposed a
temperature detection method of integrated circuit was proposed based on
photoluminescence spectra of colloidal PbSe QDs. The method for temperature
detection includes colloidal PbSe quantum dots deposited on the surface of the
printed circuit board, colloidal PbSe quantum dots of the surface are excited by
the laser and infrared spectrometer receives photoluminescence spectra. Image
acquisition system used for micron scale areas of temperature detection collects
a tiny and specific areas imaging in the surface of chip. Experiments showed that
the measurement accuracy is +/-3 degrees C and the relative error is less than
5%.
PMID- 26415422
TI - [Real-Time Stability Monitoring of Photonic Crystal Sensing System Based on
Guided-Mode Resonance Effect].
AB - The detection limit of antibody content has reached level of nanograms per
milliliter due to high sensitivity and extremely narrow band of photonic crystal
(PC) filter. The PC filter based on guided-mode resonance (GIR) effect can also
be applied to detecting the molecular interactions. As the transducing element,
one-dimensional PC filters transform biological information to photoelectric
signal on optical spectrum analyzer (OSA). The main sensing performance is the
change of peak-wavelength of PC filter. The sensing system using PC filter is
restricted to the system stability which determines the effectiveness of
detecting data. So in this paper, a detecting system we designed is briefly
addressed. The morphology and the spectrum of PC filter we fabricated are tested.
Considering the coupling light loss and integration of the system, noise signal
in spectrum is going to affect the detecting results. To monitor the influence,
realization of real-time monitoring the changes of the peak wavelength of PC
filter is mainly illustrated. The monitoring is realized by transferring
detecting data to computer in time and the results can represent the stability of
the system. The program is compiled by Lab VIEW. In our experiment, the shift of
0. 25 nm of the peak wavelength caused by vibration of platform or unsteadiness
of light source is within the sensitivity of the PC filter obtained by
simulation, so we proposed this system we mentioned can be used in sensing most
kind of bulk reagents.
PMID- 26415423
TI - The Application of Quality Identification in Honey by Photoacoustic Spectroscopy.
AB - The photoacoustic spectrum of glucose, sucrose and honey solutions in the visible
range are measured by using the single-light photoacoustic spectrometer, and are
compared with the spectra from spedtrophotometry method. The spectral
characteristics of the above solutions show that the spectral background
intensity and spectral profile have some differences for different kinds of
solutions. The spectra of the three kinds of solutions all have strong peak value
at 485 and 655 nm, but the intensity ratios between the two peaks are different.
Besides, there are characteristic peak at 475, 576 and 630 nm for glucose, and
the sucrose has apparent characteristic peak at 632 nm, these characteristic
peaks can be used for detecting whether the natural honey has been added glucose
or sucrose. By comparing two kinds of spectrum of the same solution, the
intensity of photoacoustic spectrum is more responsive to the wavelength,
indicating photoacoustic spectrometry has a higher sensitivity in the test of
material composition.
PMID- 26415424
TI - [Terahertz Spectrum Modulation with Liquid Crystal Spatial Light Modulator].
AB - Terahertz wave with modulation spectrum is valuable in many fields. Terahertz
spectrum has been modulated with a pure-phase liquid crystal spatial light
modulator by shaping the femtosecond laser beam profile. In the experiment,
terahertz wave is generated by femtosecond laser pulses in mode of Optical
Rectification and then its signals are detected by a terahertz time-domain
spectroscopy system. Phase maps obtained with the GS algorithm are loaded to get
the shaped beam profile. Therefore, Terahertz spectrum has been successfully
modulated by changing the detection range and beam profile parameters.
Simultaneously, the simulations have been performed with the Fresnel diffraction,
and they agree with the experimental results well. The results show that the
modulation of the THz spectrum with this method is feasible.
PMID- 26415425
TI - [Classification of THz Transmission Spectrum Based on Kevnel Function of Convex
Combination].
AB - In the present paper, support vector machine (SVM) based on convex combination
kernel function will be used for classification of THz pulse transmission
spectra. Wavelet transform is used in data pre-processing. Peaks and valleys are
regarded as location features of THz pulse transmission spectra, which are
injected into maximum interval features of term frequency-inverse document
frequency (TF-IDF). We can conclude weight of each sampling point from the
information theory. The weight represents the possibility that sampling point
becomes feature. According to the situation that different terahertz-transmission
spectra are lack of obvious features, we composed a SVM classification model
based on convex combination kernel function. Evaluation function should be used
as an evaluation method for obtaining the parameters of optimal convex
combination to achieve a better accuracy. When the optimal parameter of kenal
founction was determined, we should compose the model for process of
classification and prediction. Compared with the single kernel function, the
method can be combined with transmission spectroscopic features with
classification model iteratively. Thanks to the dimensional mapping process,
outstanding margin of features can be gained for the samples of different
terahertz transmission spectrum. We carried out experiments using different
samples The results demonstrated that the new approach is on par or superior in
terms of accuracy and much better in feature fusion than SVM with single kernel
function.
PMID- 26415426
TI - [Influence of Concentration Sequence on the Signal-to-Noise Ratio of Cross Peaks
of 2D Asynchronous Spectra Generated by Using the DAOSD Approach].
AB - In the present work, computer simulation was performed on a model chemical system
where two solutes (denoted as P and Q, respectively) are dissolved in the same
solution. Under intermolecular interaction between P and Q, part of P undergoes
subtle structural variation and converts into U while part of Q converts into V.
The strength of intermolecular interaction can be characterized by the
corresponding equilibrium constant K. Our preliminary studies indicate that the
S/N ratio of cross peak increases considerably as n increases. Moreover, the S/N
ratio of the cross peak from the asynchronous spectra can be improved
significantly when the suitable concentrations of P and Q are adopted. This work
is helpful for a selection of suitable concentration sequence to maximize S/N
ratio of cross peaks in the 2D asynchronous spectra generated by using the DAOSD
approach proposed in our previous study so that weak intermolecular interaction
can be probed.
PMID- 26415427
TI - [FTIR Noise Calibration in Quantitative Estimate of VOCs Concentration].
AB - The Classical Least Square regression (CLS) is one of the most popular regression
methods in FTIR quantitative estimation. However, CLS is the best unbiased
estimator only under the assumption that error (noise) in the spectrum has equal
variance, which usually is not the case in FTIR. This paper proposed a noise
calibration method for FTIR spectrum analysis. Based on measured variance of
noise in the FTIR spectrum by computer, the Weighted Least Square regression
(WLS) method is used in quantitative estimation. The experiment results showed
that the WLS performs much better than CLS in quantitative estimation of VOCs
pollution.
PMID- 26415428
TI - [FTIR and 13C NMR Analysis of Dissolved Organic Matter (DOM) in the Treatment
Process of Tannery Wastewater].
AB - Nowadays, the wastewater quantity discharged yearly from tannery industry is
around 0. 2 billion t in China. The contaminants of tannery wastewater include
macromolecular organic matters, such as grease, fur scraps and collagen, and the
alkaline wastewater appears to be of high content of salt and COD. The quality of
tannery wastewater is monitored strictly among all kinds of industry wastewater.
In the treatment process of tannery wastewater, the quality of inlet and outlet
water is generally analyzed. In fact, the transformation behavior of contaminants
should be additionally checked to optimize the treatment conditions. Dissolved
organic matter (DOM) is commonly existed in water-bodies and helpful to
understand the physicochemical characteristics, while the related work should be
further studied on tannery wastewater. The approaches of elemental analysis,
thermal gravimetric analysis (TG), Fourier infrared spectroscopy (FTIR) and 13C
nuclear magnetic resonance (13C NMR) were used to reveal the characteristics of
DOM in the treatment process of tannery wastewater. The results showed the carbon
content of DOM samples increased gradually, atomic ratios of H/C increased
firstly and then decreased, indicating the organic matters were decomposed into
chain structures firstly, finally forming the component hard to degraded. The
pyrolysis process of DOM mainly proceeded in the regions of 110~530 degrees C
(aliphatic compound, protein, etc. ) and 530~800 degrees C (aromatic ring,
single bond of C-C, etc. ). The functional groups of DOM included -OH, -NH2, C=O
and so on, and the aromatic substances were detected, shown from FTIR figures, in
the later period of the reaction, caused by the metabolism effect of micro
organism. The content of alkoxy-C increased to the maximum in the second
biochemical pond, and the minimum content of aromatic-C appeared in the second
biochemical pond, suggesting the transformation behavior of carbon functional
groups. The investigation on DOM in tannery wastewater is significant to
understand the purification mechanism of contaminants in tannery wastewater.
PMID- 26415429
TI - [Retrieval of the Optical Thickness and Cloud Top Height of Cirrus Clouds Based
on AIRS IR High Spectral Resolution Data].
AB - A study was carried out to retrieve optical thickness and cloud top height of
cirrus clouds from the Atmospheric Infrared Sounder (AIRS) high spectral
resolution data in 1070~1135 cm-1 IR band using a Combined Atmospheric Radiative
Transfer model (CART) by brightness temperature difference between model
simulation and AIRS observation. The research is based on AIRS LIB high spectral
infrared observation data combined with Moderate Resolution Imaging
Spectroradiometer (MODIS) cloud product data. Brightness temperature spectra
based, on the retrieved cirrus optical thickness and cloud top height were
simulated and compared with brightness temperature spectra of AIRS observation in
the 650~1150 cm-1 band. The cirrus optical thickness and cloud top height
retrieved were compared with brightness temperature of AIRS for channel 760
(900.56 cm-1, 11. 1 um) and cirrus reflectance of MODIS cloud product. And cloud
top height retrieved was compared with cloud top height from MODIS. Results show
that the brightness temperature spectra simulated were basically consistent with
AIRS observation under the condition of retrieval in the 650~1150 cm-1 band. It
means that CART can be used to simulate AIRS brightness temperature spectra. The
retrieved cirrus parameters are consistent with brightness temperature of AIRS
for channel 11. 1 um with low brightness temperature corresponding to large
cirrus optical thickness and high cloud top height. And the retrieved cirrus
parameters are consistent with cirrus reflectance of MODIS cloud product with
high cirrus reflectance corresponding to large cirrus optical thickness and high
cloud top height. Correlation coefficient of brightness temperature between
retrieved cloud top height and MODIS cloud top height was relatively high. They
are mostly located in the range of 8. 5~11.5 km, and their probability
distribution trend is approximately identical. CART model is feasible to retrieve
cirrus properties, and the retrieval is reliable.
PMID- 26415430
TI - [Study on the Influence of Mineralizer on the Preparation of Calcium Aluminates
Based on Infrared Spectroscopy].
AB - In this study, effect of mineralizer on the structure and spectraproperties of
calcium aluminates formation was extensively studied. Medium or low-grade bauxite
and calcium carbonate were used as raw material and mineralizer CaF2 as additive.
Calcium aluminates can be obtained after mixing fully, calcination and grinding.
The prepared calcium aluminates can be directly used for the production of
polyaluminiumchloride (PAC), polymeric aluminum sulfate, sodium aluminate and
some other water treatment agents. The calcium aluminates preparation technology
was optimized by investigating the mass ratio of raw materials (bauxiteand
calcium carbonate) and mineralizer CaF2 dosage. The structure and spectra
properties of bauxite and calcium aluminates were characterized by Fourier
transform infrared(FTIR) spectroscopy analysis and the mineralization mechanism
of the mineralizer was studied. FTIR spectra indicated that the addition of
mineralizer promoted the decomposition and transformation of the diaspore,
gibbsite and kaolinite, the decomposition of calcium carbonate, and more
adequately reaction between bauxite and calcium carbonate. In addition, not only
Ca in calcium carbonate and Si in bauxite were more readily reacted, but also Si
O, Si-O-Al and Al-Si bonds in the bauxite were more fractured which contributed
to the release of Al in bauxite, and therefore, the dissolution rate of Al2O3
could be improved. The dissolution rate of Al2O3 can be promoted effectively when
the mineralizer CaF2 was added in a mass ratio amount of 3%. And the mineralizer
CaF2 cannot be fully functioned, when its dosage was in a mass percent of 1. 5%.
Low-grade bauxite was easier to sinter for the preparation of calcium aluminates
comparing with the highgrade one. The optimum material ratio for the preparation
of calcium aluminates calcium at 1 250 degrees C was the mass ratio between
bauxite and calcium carbonate of 1 : 0. 6 and mineralizer CaF2 mass ratio percent
of 3%.
PMID- 26415431
TI - [Effects of Different Pretreatment Methods on the Phenylketonuria Screening Model
by FTIR/ATR Spectroscopy].
AB - To establish a phenylketonuria screening model by FTIR/ATR spectroscopy, and to
compare the effects of different pretreatment methods, such as baseline
correction, smoothing, derivation, Fourier deconvolution, on the model quality. A
consensus partial least squares regression method (cPLS) was used to build the
quantitative model of phenylalanine in dried blood spots. The effects of
different pretreatment methods on the model performance were investigated, using
the correlation coefficient (r), root mean square error of prediction (RMSEP),
mean relative error (MRE) and predictive accuracy (Acc). The nine-point smoothing
coupled with the first differential was found to perform the best. Compared with
the model by the original spectra, its r, RMSEP, MRE and Acc were improved from
0. 822 7, 115. 8, 0. 395 and 94. 6 to 0. 889 9, 102. 2, 0. 286 and 100,
respectively. With the advantages of fast speed, easy process, no reagents
consumption and environmental protection, the present method is expected to
become a simple and green technology for rapidly screening the neonatal
phenylketonuria in a large population.
PMID- 26415432
TI - Rapid Isolation of Phenol Degrading Bacteria by Fourier Transform Infrared (FTIR)
Spectroscopy.
AB - Phenol is an important chemical engineering material and ubiquitous in industry
wastewater, its existence has become a thorny issue in many developed and
developing country. More and more stringent standards for effluent all over the
world with human realizing the toxicity of phenol have been announced. Many
advanced biological methods are applied to industrial wastewater treatment with
low cost, high efficiency and no secondary pollution, but the screening of
function microorganisms is certain cumbersome process. In our study a rapid
procedure devised for screening bacteria on solid medium can degrade phenol
coupled with attenuated total reflection fourier transform infrared (ATR-FTIR)
which is a detection method has the characteristics of efficient, fast, high
fingerprint were used. Principal component analysis (PCA) is a method in common
use to extract fingerprint peaks effectively, it couples with partial least
squares (PLS) statistical method could establish a credible model. The model we
created using PCA-PLS can reach 99. 5% of coefficient determination and
validation data get 99. 4%, which shows the promising fitness and forecasting of
the model. The high fitting model is used for predicting the concentration of
phenol at solid medium where the bacteria were grown. The highly consistent
result of two screening methods, solid cultural with ATR-FTIR detected and
traditional liquid cultural detected by GC methods, suggests the former can rapid
isolate the bacteria which can degrade substrates as well as traditional
cumbersome liquid cultural method. Many hazardous substrates widely existed in
industry wastewater, most of them has specialize fingerprint peaks detected by
ATR-FTIR, thereby this detected method could be used as a rapid detection for
isolation of functional microorganisms those can degrade many other toxic
substrates.
PMID- 26415433
TI - [Study on Hollow Brick Wall's Surface Temperature with Infrared Thermal Imaging
Method].
AB - To address the characteristic of uneven surface temperature of hollow brick wall,
the present research adopts soft wares of both ThermaCAM P20 and ThermaCAM
Reporter to test the application of infrared thermal image technique in measuring
surface temperature of hollow brick wall, and further analyzes the thermal
characteristics of hollow brick wall, and building material's impact on surface
temperature distribution including hollow brick, masonry mortar, and so on. The
research selects the construction site of a three-story-high residential, carries
out the heat transfer experiment, and further examines the exterior wall
constructed by 3 different hollow bricks including sintering shale hollow brick,
masonry mortar and brick masonry. Infrared thermal image maps are collected,
including 3 kinds of sintering shale hollow brick walls under indoor heating in
winter; and temperature data of wall surface, and uniformity and frequency
distribution are also collected for comparative analysis between 2 hollow bricks
and 2 kinds of mortar masonry. The results show that improving heat preservation
of hollow brick aid masonry mortar can effectively improve inner wall surface
temperature and indoor thermal environment; non-uniformity of surface temperature
decreases from 0. 6 to 0. 4 degrees C , and surface temperature frequency
distribution changes from the asymmetric distribution into a normal distribution
under the condition that energy-saving sintering shale hollow brick wall is
constructed by thermal mortar replacing cement mortar masonry; frequency of
average temperature increases as uniformity of surface temperature increases.
This research provides a certain basis for promotion and optimization of hollow
brick wall's thermal function.
PMID- 26415434
TI - [Research of Straw Biomass Based on NIR by Wavelength Selection of IPLS-SPA].
AB - The whole spectrum usually contains a lot of redundant information in the near
infrared spectroscopy model, the presence of redundant information will increase
the model resolution time and increase the difficulty of parsing model,
Therefore, how to select the characteristic wavelength quickly and effectly is
very crucial. In this paper, we combined the algorithm based on SPA (successive
projections algorithm ) with IPLS (interval partial least squares ) to selec the
characteristic wavelength in the fermentation of wheat straw microbial biomass, A
total of 85 samples prepared by measuring microbial biomass using glucosamine
method, 68 samples are chosen as calibration set and 17 simples are chosen as
verification set. First, the whole spectral region 520 points are segmented
modeling according to the interval wavelength point size 10, 20, 30, 40 and 4
450~4 925 cm-1, 9 194~9 993 cm-1 two-band range are selected as the
characteristic wavelength band, then pick out the new feature wavelength points
by Successive Projections Algorithm band and Genetic Algorithm (GA),
comprehensive analysis and comparison the result of model. The experimental
results show that the using of IPLS-SPA algorithm to select the combination band
4 450~4 925 cm-1 & 9 194~9 993 cm-1 has the best modeling effect, compared with
the modeling of whole spectrum, the wavelength points decrease from 520 to 10,
the correction coefficient of determination R2 rised from 0. 884 9 to 0. 945 28,
root mean square error (RMSE) dropped from 11. 104 9 to 8. 203 3, although the
genetic algorithm model achieved the better accuracy, but the results are
instable and have a strong randomness , while IPLS combined SPA method can select
characteristic wavelength information stability and accurately, which can improve
the model calculation speed and reduce the fitting difficulty of the model, it
can be used as a new reference method for band selection. The results show that
using near infrared spectroscopy method for straw biomass rapid detection is
feasible.
PMID- 26415435
TI - [Applied Research in Grade Estimation of Surimi by Near Infrared Spectroscopy].
AB - The feasibility of utilizing near infrared spectroscopy for estimating frozen and
thawed white croaker surimi with different grades was presented in the research.
First-derivative and standard normal variable transformation were used as
pretreatment method, then principal component analysis was carried out on the
processed datas. Establish grade estimation model on white croaker surimi with
different grades by principal component analysis-mahalanobis distance pattern
recognition method. Seven kinds of physicochemical indexes (moisture, protein,
crude fat, salt-soluble protein, gel strength, water-holding ability and
whiteness) of white croaker surimi with different grades were determinated. We
came to the following conclusions. Firstly, white croaker surimi with three grade
could be distinguished effectively by principal component analysis. Secondly, the
model of grade estimation established by principal component analysis-mahalanobis
distance pattern recognition method had better performance on frozen white
croaker surimi than thawed ones, the former's comprehensive accuracy was 96. 3 %
with the latter's is 83. 3%. Thirdly, the physicochemical indexes of white
croaker surimi with different grades had some distinctions. The research
indicated that near infrared spectroscopy could estimate the grade of white
croaker surimi rapidly and nondestructively.
PMID- 26415436
TI - [Quantitative Detection of Chinese Cabbage Clubroot Based on FTIR Spectroscopy].
AB - Clubroot, caused by Plasmodiophora brassicae, is considered the most devastating
soilborne disease in Brassica crops. It has emerged as a serious disease
threatening the cruciferous crop production industry in China. Nowadays, the
detection techniques for P. brassicae are laborious, time-consuming and low
sensitivity. Rapid and effective detection methods are needed. The objective of
this study is to develop a Fourier transform infrared spectrometer (FTIR)
technique for detection of P. brassicae effectively and accurately. FTIR and Real
time PCR techniques were applied in quantitative detection of P. brassicae.
Chinese cabbages were inoculated with P. brassicae. By analyzing the FTIR spectra
of P. brassicae, infected clubroots and healthy roots, three specific bands 1
105, 1 145 and 1 228 cm-1 were selected. According to the correlation between the
peak areas at these sensitive bands and Real-time PCR Ct value, quantitative
evaluation model of P. brassicae was established based on FTIR y=34. 17 +12. 24x
9. 81x2 - 6. 05x3, r=0. 98 (p<0. 05). To validate accuracy of the model, 10
clubroot samples were selected randomly from field, and detected by FTIR spectrum
model, the results showed that the average error is 1. 60%. This demonstrated
that the FTIR technology is an available one for the quantitative detection of P.
brassicae in clubroot, and it provides a new method for quantitative and quickly
detection of Chinese cabbage clubroot.
PMID- 26415437
TI - [Measurement of Soil Total Nitrogen Using Near Infrared Spectroscopy Combined
with RCA and SPA].
AB - Visible near spectra tecnnology was adopted to detect soil total nitrogen
content. 394 soil samples were collected from Wencheng, Zhejiang province to be
used for calibration model (n=263) and independent prediction set (n=131). Raw
spectra and wavelength-reduced spectra with five different pretreatment methods
(SG smoothing, SNV, MSC, 1st-D and 2nd-D) were compared to determine the optimal
wavelength range and pretreatment method for analysis. The results with 5
different pretreatment methods were not improved compared to that both of full
spectra PLS model and wavelength reduction spectra model. Spectral variable
selection is an important strategy in spectrum modeling analysis, because it
tends to parsimonious data representation and can lead to multivariate models
with better performance. In order to simply calibration models, the wavelength
variables selected by two different variable selection methods (i. e. regression
coefficient analysis (RCA) and successive projections algorithm (SPA) were
proposed to be the inputs of calibration methods of PLS, MLR and LS-SVM models
separately. These calibration models were also compared to select the best model
to predict soil TN. In total, 9 different models were built ahd the best results
indicated that PLS, MLR and LS-SVM obtained the highest precision with
determination coefficient of prediction R2(pre) =0. 81, RMSEP=0. 0031 and RPD=2.
26 based on wavelength variables selected by RCA (0. 0002) and SPA as inputs of
models. SPA-MLR model and other three models based on 7 sensitive variables
selected by RC using 0. 0002 regression coefficient threshold value obtained the
best result with R2(pre), RMSEP and RPD as 0. 81, 0. 0031 and 2. 26. This
prediction accuracy is classied to be very good. For all the models, it could be
concluded that RCA and SPA could be very useful ways to selected sensitive
wavelengths, and the selected wavelengths were effective to estimate soil TN. It
is recommended to adopt SPA variable selection or RCA variable selection method
with both linear and nonlinear calibration models for measurement of the soil TN
using Vis-NIR spectroscopy technology, and wavelengths selection could be very
useful to reduce collinearity and redundancies of spectra.
PMID- 26415438
TI - [Characterization of Wood Surface Treated with Electroless Copper Plating by Near
Infrared Spectroscopy Technology].
AB - Wood electromagnetic shielding material, which was made by treating wood with
electroless plating, not only keep the superior characteristics of wood, but also
improve the conductivity, thermal conductivity and electromagnetic shielding
properties of wood. The emergence of this material opens the way to the value
added exploitation of wood and widens the processing and application field for
the electromagnetic shielding material. In order to explore the feasibility of
using NIR technology to investigate the properties of wood electromagnetic
shielding material, this study analysis the samples before and after copper
plated process by the NIR spectroscopy coupled with principal component analysis
(PCA). The results showed that (1) there exist significant differences between
samples before and after copper plated process both on the spectral shape and
absorption, and the great differences can also be seen in the samples with
different treat time, especially for the samples with 5 min treat time; (2) after
PCA analysis, six clusters from the samples before and after copper plated
process were separately distributed in the score plot, and the properties of
untreated wood and sensitized wood were similar, and the properties of samples
for 25 and 40 min treat time were also similar in order that these samples were
close to each other, all of which might suggest that the NIR spectroscopy
reflected major feature information about material treatment; (3) After comparing
the PCA performance between NIR and visible spectral region, it could be found
that the classification performance of samples before and after copper plated
process based on the NIR region were better than that based on the visible
region, and the information of color on the surface of samples were preferably
reflected in the visible region, which could indicate that there are more
information about samples' surface characters using the visible spectroscopy
coupled with NIR spectroscopy and it is feasible to use visible-NIR technology to
investigate the surface characteristics of natural polymers treated with
electroless copper plating.
PMID- 26415439
TI - [Investigation of the Interaction between 1,3-Dimethylurea and Solvent by Raman
Methods].
AB - Urea family plays significant role in the bio-science area. Because of the unique
frame, they can form Hydrogen bond with water as well as other substance.
Hydrogen bonds are normal weak interactions in the system of bio-molecules. A
Raman spectrum is the most powerful method to obscure the Hydrogen bond
interaction between molecules. Initially, we measure the Raman spectra of DMU
crystal, and then use density function theory with a B3LYP/6-311G* * basis set to
optimize the geometry structure and calculate the vibrational frequency of gas
phase DMU, which assigns the Raman pecks. Then, measure the solvent. When
dissolving DMU in water, the interaction between DMU-DMU will replaced by the
interaction between water-DMU. The orbital hybridization of nitrogen atoms
changes from the solid-state the sp' orbital hybridization to sp3. So, the frame
of this molecule goes from in-planet to out of plant during this process.
PMID- 26415440
TI - [Surface Enhanced Raman Spectroscopic Studies on the Coupling Effect of
Multilayer Au@SiO2 Film].
AB - The SiO2 shell with the thickness of 4 nm was attached onto high surface enhanced
Raman spectroscopy (SERS) active Au core nanoparticles to obtain Au@SiO2 core
shell nanoparticles by the hydrolysis of sodium silicate solution with the
boiling water bath. The inert shell of SiO2 isolated the direct interaction of Au
nanoparticles and probe molecules. The stable, compact and uniform monolayer
nanoparticles film was self assembled at water/oil interface, and one to six
monolayers film was transferred to Si wafer as SERS substrates through layer by
layer technique. The relationship between the SERS activities and layers of the
monolayer nanoparticles film on Si surface was investigated. The SERS mapping was
developed to determine the layers of the Au@SiO2 film. The coupling effect among
the Au@SiO2 films was explored by changing the adsorption location of the probe
on the multilayer films. The result revealed that the monolayer film was a
favourable candidate with high-quality performances for the SERS application. The
SERS signal was distributed on the surface with high uniformity at the same
monolayer film, and it was enhanced in the intensity with the increase in film
layers. It reached the maximun intensity as the film was over five layers. It
indicated that the SERS signal was contributed mainly by the first five
monolayers. The probe molecules were immobilized onto the first monolayer
nanoparticles film, and the SERS signal from the probe approached to the maximum
as the second monolayer covered the probe modified first nanoparticles film. It
was dominated by the coupling effect ("hot spots") of the adjacent layers. The
SERS signal decreased in intensity when the third layer was transferred onto the
second layer, and it disappeared after the fouth layer was covered, mainly duo to
the shield of the nanoparticles film to the incident laser and Raman signal. The
preliminary results provided guidance for fabricating optimal SERS substrates.
PMID- 26415441
TI - [Raman and EDXRF Study on Overglaze Decorations of Jingdezhen Ceramics].
AB - Overglaze decoration porcelain is an important category of ancient Chinese
ceramics, which has significant artistic value and scientific value.
Nondestructive analysis methods such as Raman spectroscopy and EDXRF were used to
analyze the overglaze decorations on the Jingdezhen ceramic samples of Yuan, Ming
and Qing Dynasty. The recipe and color mechanism of the overglaze pigments were
discussed according to the chemical composition and phase composition analysis.
The study found that dark red overglaze decorations of ancient Honglvcai, Wucai
and famille rose in Jingdezhen are colored by hematite, yellow color is lead tin
yellow, carmine decoration is colored by gold less than 0. 1 % in concentration,
and green decorations are colored by bivalent copper ion. The result also
indicates that the effective combination of Raman spectroscopy and EDXRF can play
an important role in the deep research on ceramic artifacts, especially for the
overglaze decoration pigments which are interveined each other.
PMID- 26415442
TI - [Fast Discrimination of Drugs by Improved Projection Algorithm Based on Raman
Spectroscopy].
AB - The projection algorithm used in mixture analysis to determine whether there is
unknown disturbance existing in grey system can not accurately identify different
samples and similar samples at the same time when it is used in the
identification of drugs, because of the insufficient criteria. In the present
study, one of its criteria for whether the size of measurement error of testing
sample is at a limited level is improved for whether the size and distribution of
measurement error is equal and similar between testing sample and standard
sample. By testing 6 kinds of normal drugs (including BAYER Aspirin Enteric
coated Tablets, TYLENOL Acetaminophen Sustained Release Tablets, BAYER Compound
Paracetamol Tablets(II), HUAZHONG Compound Vitamin C, HUAZHONG Vitamin B and
MADINGLIN Demperidone Tablets) and 3 kinds of similar drugs of aspirin (including
BAYER Aspirin Enteric-coated Tablets, Shanghai SINE Aspirin Enteric-coated
Tablets and Bamyl Aspirin Effervescent Tablets), it was found that the un
improved projection algorithm directly used in discrimination of drugs shows poor
performance with many problems existing, however, the improved projection
algorithm can discriminate different drugs and similar drugs with accuracy up to
100%. The improved projection algorithm can be a universal, accurate and reliable
automated pharmaceutical identification algorithm and can provide a reference for
the study on identification of substance.
PMID- 26415443
TI - [Detection of Ethoprophos Using SERS Coupled with Magnetic Fe3O4/Ag Composite
Materials].
AB - The magnetic Fe3O4/Ag composite materials were synthesized by reducing AgNO3 with
sodium citrate in the presence of Fe3O4 which were prepared by co-precipitation
firstly. The enrichment and extraction of ethoprophos assembled on Fe3O4/Ag were
achieved with the applied magnetic field. The different concentrations of
ethoprophos adsorbed on Fe3O4/Ag were analyzed by SERS and it was showed that the
trace analysis of ethoprophos had been established, while the enhancement factor
of probe molecules on Fe3O4/Ag was 1. 48 X 10(5). The structure and morphology of
Fe3O4/Ag were characterized by UV-Vis, EDX and TEM. Compared with Ag, the UV-Vis
absorption peak of Fe3O4/Ag shifted from 417 to 369 nm, and the UV-Vis of Fe3O4
almost had no characteristic absorption peak in this region. At the same time, it
was showed that the surface properties of Fe3O4/Ag changed with Raman enhancement
effect during the aggregation process of Ag around the surface of Fe3O4. Further
EDX images of micro area element analysis suggested that the chemical composition
of products were Ag, Fe and O while the Cu peak was from the copper mesh. In
addition, TEM images indicated that the average particle size of Fe3O4 was
between 30 and 60 nm with shape tended to be spherical. And the silver
nanoparticles were attached to the Fe3O4 particles and agglomeration occured.
Density functional theory calculations which can be applied to qualitative
judgment of molecule was carried out to obtain the molecular optimization
structure and theoretical Raman spectra. It was found that the stabilized SERS
signals were detected under the saturated adsorption equilibrium after 15 min.
Finally, Raman response of ethoprophos was achieved with lower than 2 X 10(-8)
mol . L-1 , indicatint that the established method had reached the requirements
of ethoprophos residues detection and could be used for analysis of sulfur
containing organophosphorus pesticide.
PMID- 26415444
TI - [Locally Dynamically Moving Average Algorithm for the Fully Automated Baseline
Correction of Raman Spectrum].
AB - The baseline correction is an, extremely important spectral preprocessing step
and can significantly improve the accuracy of the subsequent spectral analysis
algorithm. At present most of the baseline correction algorithms are manual and
semi-automated. The manual baseline correction depends on the user experience and
its accuracy is greatly affected by the subjective factor. The semi-automated
baseline correction needs to set different optimizing parameters for different
Raman spectra, which will be inconvenient to users. In this paper, a
locally.dynamically moving average algorithm (LDMA) for the fully automated
baseline correction is presented and its basic ideas.and steps are demonstrated
in detail. In the LDMA algorithm the modified moving averaging algorithm (MMA) is
used to strip the Raman peaks. By automatically finding the baseline subintervals
of the raw Raman spectrum to divide the total spectrum range into multi Raman
peak subintervals, the LDMA algorithm succeed in dynamically changing the window
half width of the MA algorithm and controlling the numbers of the smoothing
iterations in each Raman peak subinterval. Hence, the phenomena of overcorrection
and under-correction are avoided to the most degree. The LDMA algorithm has
achieved great effect not only to the synthetic Raman spectra with the convex,
exponential, or sigmoidal baseline but also to the real Raman spectra.
PMID- 26415445
TI - [A De-Noising Algorithm for Fluorescence Detection Signal of Mineral Oil in Water
by SWT].
AB - Fluorescence analysis is an important means of detecting mineral oil in water
pollutants because of high sensitivity, selectivity, ease of design, etc. Noise
generated from Photo detector will affect the sensitivity of fluorescence
detection system, so the elimination of fluorescence signal noise has been a hot
issue. For the fluorescence signal, due to the length increase of the branch set,
it produces some boundary issues. The dbN wavelet family can flexibly balance the
border issues, retain the useful signals and get. rid of noise, the de-noising
effects of dbN families are compared, the db7 wavelet is chosen as the optimal
wavelet. The noisy fluorescence signal is statically decomposed into 5 levels via
db7 wavelet, and the thresholds are chosen adaptively based on the wavelet
entropy theory. The pure fluorescence signal is obtained after the approximation
coefficients and detail coefficients quantified by thresholds reconstructed.
Compared with the DWT, the signal de-noised via SWT has the advantage of
information integrity and time translation invariance.
PMID- 26415446
TI - [Light Absorption Characteristics of FeS2-Fe1-xS Heterostructures Synthesized
under Hydrothermal Conditions].
AB - Fe-S series, especially FeS2 and Fe1-x S is the main component of crustal rocks
as important metal sulphides. Pyrite (FeS2) shows a promising vision in solar
cell materials for its high absorption coefficient and suitable band gap.
Predecessors have done some researches on the photovoltaic properties of Fe-S
series under different conditions. However, little researches have been done on
the coexisted sulphide of FeS2 and Fe1-xS. FeS2 and Fe1-xS often appear as
symbiotically due to their similar formation conditions. So the study on the
optical absorption characteristics of FeS2 and Fe1-xS are of important
significance. In order to study the optical absorption characteristics of FeS2
Fe1-xS heterostructures, using the SEM and XRD to characterize the morphology,
composition and structure, respectively. The results show that the samples were
cubic pyrite with a certain amount of pyrhotite (Fe1-xS). The crystal partical
size was between 5 and 10 nm. Measurement of the absorption spectrum was
performed using Cary 500 UV-Vis-NIR spectrophotoineter, acquiring the results of
1 860-1 889 nm, and the absorption peak in 1879nm. According to the band gap (eV)
formula, the band gap value is calculated to be 0. 657 8 eV. The extreme
electrical-to-optical conversion efficiency achieved was about 15%. By the first
principles, we analysed the reason of the changing of the band gap value, and
then compared the result with previous one. The internal structure of mineral is
the important factor affecting the photoelectric conversion. The light absorption
characteristics of FeS2-Fel-xS heterostructures synthesized under hydrothermal
conditions is better than the characteristics from natural pyrite with defects of
Co and Ni. The heterostructures can improve the electrical-to-optical conversion
efficiency and provide scientific basis for the absorption characteristics
research of Fe-S series materials.
PMID- 26415447
TI - Effect of Exogenous Phytase Addition on Soil Phosphatase Activities: a
Fluorescence Spectroscopy Study.
AB - The utilization of organic phosphorus (P) has directly or indirectly improved
after exogenous phytase was added to soil. However, the mechanism by which
exogenous phytase affected the soil phosphatases (phosphomonoesterase and
phosphodiesterase) activities was not clear. The present work was aimed to study
red soil, brown soil and cinnamon soil phosphomonoesterase (acid and alkaline)
(AcP and AlP) and phosphodiesterase (PD) activities responding to the addition of
exogenous phytase (1 g phytase/50 g air dry soil sample) based on the
measurements performed via a fluorescence detection method combined with 96
microplates using a TECAN Infinite 200 Multi-Mode Microplate Reader. The results
indicated that the acid phosphomonoesterase activity was significantly enhanced
in red soil (p<=0. 01), while it was significantly reduced in cinnamon soil;
alkaline phosphomonoesterase activity was significantly enhanced in cinnamon soil
(p<= 0. 01), while it was significantly reduced in red soil; phosphodiesterase
activity was increased in three soils but it was significantly increased in brown
soil (p<=0. 01) after the addition of exogenous phytase. The activities still
remained strong after eight days in different soils, which indicated that
exogenous phytase addition could be enhance soil phosphatases activities
effectively. This effect was not only related to soil properties, such as pH and
phosphorus forms, but might also be related to the excreted enzyme amount of the
stimulating microorganism. Using fluorescence spectroscopy to study exogenous
phytase addition influence on soil phosphatase activities was the first time at
home and abroad. Compared with the conventional spectrophotometric method, the
fluorescence microplate method is an accurate, fast and simple to use method to
determine the relationships among the soil phosphatases activities.
PMID- 26415448
TI - The Fluorescence Enhancement of Mercury Detected in Food Based on Rhodamine
Derivatives.
AB - Recently, the problem of food security is more and more serious, and people pay
attention to mercury because of the toxic of it. A new approach for the
determination of mercury content in foodstuff is devised. In this paper, first,
we design and synthesis a new kind of fluorescent probe whose matrix based on
rhodamine B, hydrazine hydrate and hydroxy benzaldehyde. Through the analysis of
H-NMR spectra of the synthesized product L1, we confirm that the synthetic
substance is the adjacent carboxyl benzaldehyde hydrazone structure generation of
rhodamine B. Then, we measure the fluorescence signal intensity of the probe with
different concentrations of mercury ions fully upon complexation by fluorescence
spectrometer and we can study the relationship between the mercury ion
concentration and the fluorescence intensity and draw the standard working curve.
Following, It's time to discuss the microwave digestion processing of tea, after
digestion we use the synthetic probe Li for determination of mercury content in
tea. The experimental results show that the maximum excitation wavelength of the
probe and coordination compound are 568. 05 and 560. 00 nm, the maximum emission
wavelength are 587. 94 and 580. 00 nm. Then we can find the best testing
conditions to improve the degree of accuracy, that is: room temperature, 50% the
methanol solution, 3. 0 mL pH 4. 0 buffer solution, in the extent of 30 min. The
experimental results show that Na+, K+, Ca2+, Cu2+, Zn2+, Al3+ have little impact
on the fluorescence intensity of the:probe. Fe3+, Mg2+, Ba2+ has a weak
enhancement to the fluorescence intensity of the probe. While a low
concentrations of Hg2+ have an obviously enhanced effect on the fluorescence
intensity of the probe. In contrast to other metal ions, the probe for Hg2+ has a
good selectivity. Linear relationship between the magnitude of increase in
fluorescence intensity and concentration of mercury ion was in the range of 5~20
ng . L-1 with detection limit (3S/N) of 1. 9 ng . L-1. The proposed method was
applied to determination of mercury ion in samples of tea and sausage and the
obtained result and sample recovery were all satisfactory. The methods of
analysis instrument has the advantages of simple structure, sensitivity, high
accuracy, good selectivity and less volume of simple, without the need for
enrichment, being very practical.
PMID- 26415449
TI - [Fluorescence Determination of Trace Se with the Hydride-K13-Rhodamine 6G
System].
AB - Se is a necessary trace element for human and animals, but the excess intake of
Se caused poison. Thus, it is very important to determination of Se in foods and
water. The target of this study is development of a new, sensitive and selective
hydride generation-molecular fluorescence method for the determination of Se. In
0. 36 mol . L-1 sulfuric acid, NaBH4 as reducing agent, Se (IV) is reduced to H2
Se. Usin3-g I solution as absorption liquid3, I- is reduced to I- by H2Se. When
adding rhodamine 6G, Rhodamine 6G and I3- form association particles, which lead
to the fluorescence intensity decreased. When Se(IV) existing, Rhodamine 6G and
I3- bind less, And the remaining amount of Rhodamine 6G increase. So the
fluorescence intensity is enhanced. The analytical conditions were optimized, a
0. 36 ml . L-1 H2SO4, 21. 6.g . L-1 NaBH4, 23.3 um . L-1 rhodamine 6G, and 50
umol . L-1 KI3 were chosen for use. When the excitation wavelength is at 480nm,
the Rayleigh scattering peak does not affect the fluorescence recording, and was
selected for determination of Se. Under the selected conditions, Se(IV)
concentration in the 0. 02~0. 60 ug . mL-1 range and the increase value of the
fluorescence intensity (DeltaF) at 562 nm linear relationship. The linear
regression equation is DeltaF562 nm =12. 6c + 20. 9. The detecton limit was 0.01
u.g . L-1. The influence of coexistence substances on the hydride generatin
molecular fluorescence determination of 5. 07 X10(-6) mol . L-1 Se(IV) was
considered in details. Results showed that this new fluorescence method is of
high selectivity, that is, 0. 5 mmol. L-1 Ba2+, Ca2+, Zn2+ and Fe3+, 0. 25 mmol .
L-1 . Mg2+, 0. 05 mmol . L-1 K+, 0. 2 mmol . L-1 Al3+, 0. 025 mmol . L-1 Te(VI)
do not interfere with the determination. The influence of Hg2+, CD2+ and Cu2+
that precipitate with Se(IV), can be eliminated by addition of complex reagent.
This hydride generation-molecular fluorescence method has been applied to
determination of trace Se in water samples,
PMID- 26415450
TI - [Determination of Trace Boron Based on Gold Nanorod Plasmonic Resonance Rayleigh
Scattering Energy Transfer to the Coordinate].
AB - B is a necessary trace element for human and animals, but the excess intake of B
caused poison. Thus, it is very important to determination of B in foods and
water. The target of this study is development of a new, sensitive and selective
resonance Rayleigh scattering energy transfer (RRS-ET) for the determination of
B. The combination of energy transfer with resonance Rayleigh scattering (RRS)
has developed a new technology called RRS-ET, which can realize selective and
sensitive detection of boric acid. The gold nanorods in diameter of 12 nm and
length of 37 nm were prepared by the seed growth procedure. In pH 5. 6 NH4 Ac-HAc
buffer solution and in the presence of azomethine-H (AMH), the gold nanorod
particles exhibited a strong resonance Rayleigh scattering (RRS) peak at 404 nm.
In the presence of boric acid, it reacts with AMH to form AMH-boric acid (AMH-B)
complexes. When the complexe as a receptor close to the gold nanorod as a donor,
the resonance Rayleigh scattering energy transfer (RRS-ET) take placed that
resulted in the Rayleigh scattering signal quenching. With the increase of the
concentration of boric acid, the formed complexes increased, the scattering light
energy of gold nanorod transfer to the complexes increased, resulting in the
Rayleigh scattering intensity linearly reduced at 404 nrn. The decreased RRS
intensity responds linearly to the concentration of boron over 10~750 ng . mL-1
B, with a regress equation of DeltaI404 nm =3. 53c+24 and a detection of 5 ng mL
1 B. The influence of coexistence substances on the RRS-ET determination of 2. 3
X 10(-7) mol . L-1 B was considered in details. Results showed that this new RRS
ET method is of high selectivity, that is, 4 X 10(-4) mol . L-1 Mn2+, Cd2+, Zn2+,
Bi+, Na+, Al3+, glucose, Hg2+, IO3-, F-, SO(2-)3, SiO3-, NO3-, CIO4-, H2O2,
mannitol, glycerol, and ethylene glycol, 4X 10(-5) mol . L-1 L-tyrosine, and 2 X
10(-4) mol . L-1 L-glutamic acid do not interfere with the determination. Based
on this, a new sensitive, selective, simple and rapid RRS-ET method has been
developed for the determination of trace boron in six mineral water samples that
contain 24. 9, 29. 3, 57. 9, 59. 0, 84. 9, and 105. 1 ng . mL-1 B, with relative
standard deviation of 1. 6%~ 4. 1% and recovery of 95. 61~9. 6%.
PMID- 26415452
TI - [Optimizing Color Rendering for Mixed-Color White Light LED].
AB - To optimize color rendering of mixed-color LEDs, the Gaussian model was used to
analyze the color-mixed LED's spectrum power distribution. The peak wavelength
"lambdam", spectral half width "Deltalambda" and amplitude "A" were basic
parameters for optimizing color rendering R9, which is very important for objects
to be colorful and vivid under the white light LED's'illuminating. The typical
methods for color mixing were used to get white light LEDs. Result was that to
get the satisfied color rendering index, one of the color primaries should be
certain and then other color primaries would be analyzed through changing three
basic parameters step by step. It was concluded that the analysis in this paper
would be referential to optimize the color-mixed white LED's color rendering.
PMID- 26415451
TI - [Study of Determination of Oil Mixture Components Content Based on Quasi-Monte
Carlo Method].
AB - Gasoline, kerosene, diesel is processed by crude oil with different distillation
range. The boiling range of gasoline is 35 ~205 degrees C. The boiling range of
kerosene is 140~250 degrees C. And the boiling range of diesel is 180~370
degrees C. At the same time, the carbon chain length of differentmineral oil is
different. The carbon chain-length of gasoline is within the scope of C7 to C11.
The carbon chain length of kerosene is within the scope of C12 to C15. And the
carbon chain length of diesel is within the scope of C15 to C18. The recognition
and quantitative measurement of three kinds of mineral oil is based on different
fluorescence spectrum formed in their different carbon number distribution
characteristics. Mineral oil pollution occurs frequently, so monitoring mineral
oil content in the ocean is very important. A new method of components content
determination of spectra overlapping mineral oil mixture is proposed, with
calculation of characteristic peak power integrationof three-dimensional
fluorescence spectrum by using Quasi-Monte Carlo Method, combined with optimal
algorithm solving optimum number of characteristic peak and range of integral
region, solving nonlinear equations by using BFGS(a rank to two update method
named after its inventor surname first letter, Boyden, Fletcher, Goldfarb and
Shanno) method. Peak power accumulation of determined points in selected area is
sensitive to small changes of fluorescence spectral line, so the measurement of
small changes of component content is sensitive. At the same time, compared with
the single point measurement, measurement sensitivity is improved by the decrease
influence of random error due to the selection of points. Three-dimensional
fluorescence spectra and fluorescence contour spectra of single mineral oil and
the mixture are measured by taking kerosene, diesel and gasoline as research
objects, with a single mineral oil regarded whole, not considered each mineral
oil components. Six characteristic peaks are selected for characteristic peak
power integration to determine components content of mineral oil mixture of
gasoline, kerosene and diesel by optimal algorithm. Compared with single point
measurement of peak method and mean method, measurement sensitivity is improved
about 50 times. The implementation of high precision measurement of mixture
components content of gasoline, kerosene and diesel provides a practical
algorithm for components content direct determination of spectra overlapping
mixture without chemical separation.
PMID- 26415453
TI - [Differential Reflectance Spectroscopy for In-Situ Monitoring of Organic Thin
Films Growth in Vacuum Environment].
AB - For realizing the real-time monitoring of organic thin film preparation process
in vacuum environment, the present paper proposes a high precision measurement
approach based on differential reflectance spectroscopy (DRS). An optical system
was constructed with off the shelf optical components, such as off-axis parabolic
mirror, optical flat and optical fiber. A differential algorithm was employed to
analyze the spectral signals. Based on the homebuilt setup, instability induced
by variation of temperature was investigated. It was concluded that with the good
control of temperature and air flow, the measurement repeatability of this system
is better than 2 per thousand for a long-term period. Furthermore, an initial
stage of organic thin film growth of pentacene molecules on the surface of Au was
studied. As compared with the data of film thickness gauge and atomic force
microscope, DR spectra accurately recorded the fine optical evolution with sub
monolayer resolution, which is related to the growth of the thin film. As a
result, the DR optical system exhibits characteristics of broad spectrum (range
from 300 to 820 nm), high stability (repeatability better than 2X 10(-3)), and
high precision (sub-monolayer resolution) after efforts were done to decrease the
influences on the spectral quality produced by misalignments of the optical
components, the defects of the optics, and the disturbances of the environmental
conditions. It is indicated that the proposed DR method is suitable for real-time
online monitoring of thin film growth with high precision.
PMID- 26415454
TI - [Building Change Detection Based on Multi-Level Rules Classification with
Airborne LiDAR Data and Aerial Images].
AB - The present paper proposes a new building change detection method combining Lidar
point cloud with aerial image, using multi-level rules classification algorithm,
to solve building change detection problem between these two kinds of
heterogeneous data. Then, a morphological post-processing method combined with
area threshold is proposed. Thus, a complete building change detection processing
flow that can be applied to actual production is proposed. Finally, the
effectiveness of the building change detection method is evaluated, processing
the 2010 airborne LiDAR point cloud data and 2009 high resolution aerial image of
Changchun City, Jilin province, China; in addition, compared with the object
oriented building change detection method based on support vector machine (SVM)
classification, more analysis and evaluation of the suggested method is given.
Experiment results show that the performance of the proposed building change
detection method is ideal. Its Kappa index is 0. 90, and correctness is 0. 87,
which is higher than the object-oriented building change detection method based
on SVM classification.
PMID- 26415455
TI - [Preliminary Investigation of the Amount, the Molecular Weight and the Activity
of Polysaccharides from Chaenomeles Speciosa Fruits in Ethanol Fractional
Precipitation].
AB - Chaenomeles speciosa fruits were extracted using water. The extracts were
precipitated with 20%~95% (phi) ethanol, respectively. The amount of total
polysaccharide was measured with phenol-sulfuric acid method. A method using high
performance size-exclusion chromatography (HPSEC) equipped with multiangle laser
light-scattering photometry (MALLS) and differential refractometry (RI) was
presented for determining the molecular weight and molecular weigh distribution.
RAW264.7 macrophage were cultured and stimulated with the polysaccharides in
vitro and the production of nitric oxide in the cells was determined by the
Griess assay. The aim of the study is to determine the amount and the molecular
weight of the polysaccharides from Chaenomeles speciosa fruits, and preliminary
investigate the immunomodulatory activity, The study provided the basis datas for
the further research of Chaenomeles speciosa fruits. , and provided a simple and
system method for the research of natural polysaccharide. The ethanol fractional
precipitation showed that the order of total polysaccharide content was
95%>80%>40% >=60%>20%. The results indicated that most polysaccharide from
Chaenomeles speciosa fruits might be precipitated when ethanol concentration was
up to 95% (T) and the crude polysaccharide purity had risen from 35. 1% to 45. 0%
when the concentration of ethanol increased from 20% to 95%. HPSEC-MALLS-RI
system showed that all the polysaccharide samples had the similar compositions.
They appeared three chromatographic peaks and the retention time were not
apparently different. The Mw were 6. 570 X 10(4) g . mol-1 and 1. 393 X 10(4) g .
mol-1 respectively, and one less than 10 000 which was failure to obtain accurate
values. The molecular weight of the first two polysaccharide distribution
index(Mw/Mn)were 1. 336 and 1. 639 respectively. The polysaccharide samples had
not exhibited immunomodulatory activity assessed on the basis of nitric oxide
production by RAW264. 7 macrophage cells in the experiment.
PMID- 26415456
TI - [Relationship between the Trypsin Activity and Conformational Change Caused by
Ultra High Static Pressure].
AB - Trypsin was treated by high pressure technology, and its spatial structure was
changed, the relationship between structural changes and trypsin activity was
investigated. The secondary structure change of trypsin after pressure treatment
was observed by Fourier transform infrared spectroscopy(FTIR). Moreover its
tertiary structure change was observed by fluorescence spectroscopy; and its
activity was tested using Folin phenol method. The results showed that, compared
with the untreated(0.1 MPa), trypsin activity change was significant(p<0. 05)
under different pressure(100~600 MPa) treatment at 37 degrees C for 20 min.
After treated with 300 MPa, its activity was 0. 386 times higher than the
untreated. Secondary structure of trypsin was analysed using FTIR, and the peak
area ratio of alpha-helix and beta-tum in secondary structure was the maximum(2.
749); Endogenous fluorescence spectra intensity was the maximum (1 353) at
excitation wavelength 295 nm, and was 4 262 at excitation wavelength 280 nm;
exogenous fluorescent spectra intensity was 2 022 at excitation wavelength 228
nm, all these change was remarkable(p<0. 05) comparing with the untreated.
Therefore, ultrahigh pressure processing influence on the spatial structure of
trypsin and induce enzyme activity.change. Trypsin activity is relate to the peak
area ratio of alpha-helix and beta-turn and the exposure degree of Trp and other
hydrophobic a mino acid residues and Tyr.
PMID- 26415457
TI - Synthesis, Structure and Spectroscopy Study of a 1D Copper Coordination Polymer
Based on a Carboxybenzyl Viologen Ligand and SCN-Anion.
AB - A zwitterionic viologen derivative ligand, 1,1'-bis(4-carboxybenzyl)-4 4'
bipyridinium dichloride (H2BpybcCl2) as a multifunctional ligand, has been
synthesized incorporating a 4,4'-bipyridine core with two carboxylate groups as
a. building block, specifically designed for the rational construction of metal
organic frameworks. H2BpybcCl2 ligand is a multifunctional ligand that contains
viologen's specific functions and carboxylate coordination groups. The
coordination polymers of viologen carboxylate with copper thiocyanate are not
reported to date. A novel copper coordination polymer, [Cu(SCN)2 (Bpybc)] (I) was
by solution diffusion method and characterized by single-crystal X-ray
diffraction, XRD, elemental analyses, IR spectroscopy, UV-Vis DRS, TG analysis
and liquid-state luminescent properties. Compound I crystallized in the
monoclinic system with C2/c space group. Crystal data for complex I is as follow:
a=19. 508(4) A, b=9. 474(2) A, c =16. 963(3) A, alpha=90 degrees , beta=124.
92(3) degrees , gamma=90 degrees . Two SCN-anions were coordinated to the Cu2+
cation forming a [Cu(SCN)2] unit. Complex I was built up by [Cu(SCN)2] units
bridged sequentially by ladder-shaped Bpybc ligands to form one-dimensional
zigzag chains running along the [203] direction. The chains were held together by
pi-pi interaction between the pyridine rings and phenyl rings, thus yielding a 3
D extended supramolecular network. The UV-Visible absorption spectra show the
absorption bands of pi-pi* transitions of Bpybc ligands and d-->d transition of
Cu2+. The liquid-state luminescent property of compound I was investigated at
room temperature. Attractively, the complex exhibits strong blue emission peak at
533 nm (lambdaEx=360 nn) that can be assigned to intraligand transition of Bpybc
ligand when it was excited at 360 nm.
PMID- 26415458
TI - Crop Classification Based on Time Series MODIS EVI and Ground Observation for
Three Adjoining Years in Xinjiang.
AB - There is a regular use of Moderate Resolution Imaging Spectroradiometer (MODIS)
250 meter EVI to classify the crops on a regional level throughout the world. A
rapid agricultural land use change attributed to new Chinese agriculture policy
is attracting many researchers to focus. The objective of this study is to
present a more straightforward multiyear classification methodology using time
series MODIS EVI with 250 meters spatial resolution and subsequent field data in
Xinjiang, China. An extensive polygon based ground reference annual crop data
were collected for the years 2011, 2012 and 2013 throughout the study area. The
most pure pixel within each polygon was selected which eases crop
differentiation. Artificial Immune Network (ABNet) was used to classify cotton,
maize, wheat/others, rice and grapes, dominating most of the study area. The data
of two different years were used together to classify the crop of next year, as
2011 and 2012 were used to classify crops of 2013. Classification results were
validated using the same year ground data. Results showed the classification
accuracy above 80% for each year with kappa coefficient of 0. 7 and above.
However more research and additional ground reference data are needed to classify
a range of crops in the study area which will give a more detailed view of the
land use land cover change strengthening agriculture decisions practices in the
future.
PMID- 26415459
TI - [Estimating Leaf Area Index of Crops Based on Hyperspectral Compact Airborne
Spectrographic Imager (CASI) Data].
AB - The fast estimation of leaf area index (LAI) is significant for learning the
crops growth, monitoring the disease and insect, and assessing the yield of
crops. This study used the hyperspectral compact airborne spectrographic imager
(CASI) data of Zhangye city, in Heihe River basin, on July 7, 2012, and extracted
the spectral reflectance accurately. The potential of broadband and red-edge
vegetation index for estimating the LAI of crops was comparatively investigated
by combined with the field measured data. On this basis, the sensitive wavebands
for estimating the LAI of crops were selected and two new spectral indexes (NDSI
and RSI) were constructed, subsequently, the spatial distribution of LAI in study
area was analyzed. The result showed that broadband vegetation index NDVI had
good effect for estimating the LAI when the vegetation coverage is relatively
lower, the R2 and RMSE of estimation model were 0. 52, 0. 45 (p<0. 01) ,
respectively. For red-edge vegetation index, CIred edge took the different crop
types into account fully, thus it gained the same estimation accuracy with NDVI.
NDSI(569.00, 654.80) and RSI(597.60, 654.80) were constructed by using waveband
combination algorithm, which has superior estimation results than NDVI and CIred
edge. The R2 of estimation model used NDSI(569.00, 654.80) was 0. 77(p<0. 000 1),
it mainly used the wavebands near the green peak and red valley of vegetation
spectrum. The spatial distribution map of LAI was made according to the
functional relationship between the NDSI(569.00, 654.80) and LAI. After analyzing
this map, the LAI values were lower in the northwest of study area, this
indicated that more fertilizer should be increased in this area. This study can
provide technical support for the agricultural administrative department to learn
the growth of crops quickly and make a suitable fertilization strategy.
PMID- 26415460
TI - [Hyperspectral Band Selection Based on Spectral Clustering and Inter-Class
Separability Factor].
AB - With the development of remote sensing technology and imaging spectrometer, the
resolution of hyperspectral remote sensing image has been continually improved,
its vast amount of data not only improves the ability of the remote sensing
detection but also brings great difficulties for analyzing and processing at the
same time. Band selection of hyperspectral imagery can effectively reduce data
redundancy and improve classification accuracy and efficiency. So how to select
the optimum band combination from hundreds of bands of hyperspectral images is a
key issue. In order to solve these problems, we use spectral clustering algorithm
based on graph theory. Firstly, taking of the original hyperspectral image bands
as data points to be clustered , mutual information between every two bands is
calculated to generate the similarity matrix. Then according to the graph
partition theory, spectral decomposition of the non-normalized Laplacian matrix
generated by the similarity matrix is used to get the clusters, which the
similarity between is small and the similarity within is large. In order to
achieve the purpose of dimensionality reduction, the inter-class separability
factor of feature types on each band is calculated, which is as the reference
index to choose the representative bands in the clusters furthermore. Finally,
the support vector machine and minimum distance classification methods are
employed to classify the hyperspectral image after band selection. The method in
this paper is different from the traditional unsupervised clustering method, we
employ spectral clustering algorithm based on graph theory and compute the
interclass separability factor based on a priori knowledge to select bands.
Comparing with traditional adaptive band selection algorithm and band index based
on automatically subspace divided algorithm, the two sets of experiments results
show that the overall accuracy of SVM is about 94. 08% and 94. 24% and the
overall accuracy of MDC is about 87. 98% and 89. 09%, when the band selection
achieves a relatively optimal number of clusters using the method propoesd in
this paper. It effectively remains spectral information and improves the
classification accuracy.
PMID- 26415461
TI - [Effect of Foliar Dustfall Content (FDC) on High Spectral Characteristics of Pear
Leaves and Remote Sensing Quantitative Inversion of FDC].
AB - The precipitation of floating and sinking dust on leaves of plants is called as
foliar dustfall. To monitor foliar dustfall, it will provide fundamental basis
for environmental assessment and agricultural disaster evaluation of dust area.
Therefore, the aim of this work to (1) study the effect of foliar dustfall
content (FDC) on high spectral characteristics of pear leaves, (2) analyze the
relationship between reflectances and FDC, and (3) establish high spectral remote
sensing quantitative inversion model of FDC. The results showed that FDC
increased reflectances of visible band (400~700 nrn) with maximum band of 666 nm.
Absolute and relative rates of change were -10. 50% and -62. 89%, respectively.
The FDC decreased reflectances of near infrared band (701 ~ 1 050 nm) with
maximum band of 758 nm. Absolute and relative rates of change were 12. 04% and
41. 75%, respectively. After dustfall was removed, reflection peak of green light
and absorption valley of red and blue light became prominent, and slope of
500~750 nm wake band increased when FDC was more than 20 g . m-2. While FDC just
slightly affected shape and area of reflection peak of green light when FDC was
less than 20 g . m-2. FDC were positive and negative correlated with reflectances
of visible band and near infrared band, respectively. Maximum correlation
coefficient (0. 61) showed at 663 nm. All of 7 inversion models, the model based
on the first-order differential of logarithm of the reciprocal had better
stability and predictive ability. The coefficient of determination(R2), root mean
square error (RMSE) and relative percent deviation (RPD) of this model were 0.
78, 3. 37 and 2. 09, respectively. The results of this study can provide a
certain reference basis for hyperspectral remote sensing of FDC.
PMID- 26415462
TI - Research and Evaluation on Wear in Power-Shift Steering Transmission Through Oil
Spectral Analysis with RKPCA Method.
AB - The most common methodology used in element concentration measurement and
analyzing of wear particles is Atomic emission (AE) spectroscopy. The present
paper presents an evaluation method on wear in power-shift steering transmission
(PSST). By removing the problematic components which were highly correlated with
oil additives, the robust kernel principal component analysis (RKPCA) method and
the principal component analysis (PCA) method were accessed to extract the
principal components of spectral data for oil samples collected from the life
cycle test of PSST in different stage and to calculate the amount of each
principal component and its contribution rate respectively. A comparison between
the above mentioned two methods was made to show that RKPCA method has fewer
amounts of principal components and higher cumulative contribution rate
indicating that RKPCA method acts more effectively in variable dimension
reduction due to the outliers and nonlinearity of spectral data. Therefore, the
effectiveness of RKPCA method in classification and identification of the wear in
friction pairs was demonstrated subsequently. through the correlation analysis
between the variable coefficients of RKPCA and metal elements of friction pairs.
The demonstration showed that RKPCA functioned precisely in the classification
and identification of the wear in friction pairs, and in the evaluation on the
wear in PSST. Thereafter, to detect the threshold point where the wear took
place, the fuzzy C-means clustering algorithm was introduced to classify the
RKPCA eigenvalues, and the results were compared with that of the spectral
clustering algorithm. The fuzzy C-means clustering algorithm showed higher
sensitivity in detecting the threshold point indicting a more precise evaluation
on the wear in PSST. It is clear that the introduction of RKPCA method in wear
evaluation, which takes the eigenvalues of spectral data as a critical variable
to classify and identify the wear in different friction pairs as well as in the
integral PSST configuration, shows better accuracy in wear prediction and will
contribute to the reliable determination of life between overhauls and the
accurate positioning of worn-out parts. As might be expected, the proposed method
can be extended to other cases of wear detection and evaluation in complex
mechanical system.
PMID- 26415463
TI - [Application of LIBS in Element Analysis of Nanometer Thin Film Prepared on
Silicon Basement].
AB - In order to develop a method to analyze the metal elements in the thin film
samples rapidly, directly and without sample preparation, a laboratory LIBS
system was established recently for nanometer film analysis. This system could
determine the position of sample plane, observe the profiles of sample after
pulse-material interaction and detect the plasma morphologyand spectral emission
at the same time. Samplesused were ZrO2 films about 40 nm thickness prepared on
Si by a sol-gel process, and they were located on a manual X-Y-Z translational
stage with theaccuracy of 0. 01 mm. Final results showed that the positional
accuracy is about 20uLm with the help of two CW lasers, and the RSD of
repeatability of single-shot spectra could be to 1. 6%. We investigated special
morphology of plasma, variation tendency of signal intensity as a function of
pulse energy, LTSD (laser focus to sample distance) and time, which provide
cornerstone for optimizing experimental parameters under the conditions of room
temperature and atmospheric pressure. We calculated plasma temperature by way of
Boltzmann curve and electron density through the acquired data. We also appraised
necessary LTE conditions for quantitativeanalysis.
PMID- 26415464
TI - [Comparative Experiment and Spectrometric Analysis on Characteristics of Enclosed
Inductively Coupled Plasma].
AB - In the present paper, the spectrum analytic method was used to comparatively
study the ICP electron density distribution through two typical ICP sources
(spiral-type and planar-type) in closed quartz chamber. The E-H mode transition
of inductively coupled plasma and power coupling efficiency were researched
through the change in the relative intensity of argon ion spectral line (476. 45
nm). Electron density distribution on the antennas-vertical plane of different
ICP source was calculated through non-hydrogen-like Stark broadening of spectral
line method. The test results show that the ICP electronic density distribution
in H-mode discharge is significantly impacted by skin current of alternating
magnetic field. The skin depth decreases with the increase in discharge power.
Meanwhile, the bulk of the main plasma narrows and electron density increases. On
the vertical plane of the antenna, electron density distribution presents center
symmetry by spiral-ICP source and bimodal by planar-ICP source. The power
coupling efficiency is directly affected bysource antenna shape and capacitive
coupling effect. The relative intensity of the argon spectrum shows that the
power coupling efficiency of spiral-type source is lower than that of planar-type
source. The proposed experimental method provides a way to obtain a plasma source
in closed quartz cube chamber with the highest electron density ranging from 1.
4X 10(17) to 2. 5 X 10(17) m-3 (spiral-ICP source) and 1. 8 X 10(17) to 3. 0 X
10(17) m-3 (planar-ICP source).
PMID- 26415465
TI - [Determination of SiO2 in Groundwater and Mineral Water by Inductively Coupled
Plasma-Atomic Emission Spectrometry].
AB - The concentration of silica in groundwater and mineral water was determined by
inductively coupled plasma-atomic emission spectrometry (ICP-AES). After a more
sensitive analytical line of silicon was chosen, the effects of operating
conditions of the ICP spectrometer on the analysis results were investigated, at
the same time, the impact of coexisting ions on determination results of SiO2 was
also considered and eliminated. The transmit power of 1 350 W, observation height
of 12 mm, the nebulizer pressure of 0. 20 MPa and the pump speed of analysis of
75 r . min-1 were selected by experimental conditions. Under the optimum
analytical conditions of spectrometer, the method was used for the determination
of SiO2 in groundwater and mineral water with the detection limit of 0. 017. mg .
L-1, recoveries between 94. 10% and 103. 8%, and relative standard deviation
(RSD)s<=3. 06%. Compared with the results of silicon molybdenum yellow
spectrophotometry, the results were basically consistent with the relative
deviation <=3. 00%. In conclusion, the method is simple and efficient with high
precision and accuracy, and can be used for research and routine production.
PMID- 26415466
TI - [Influence of Spectral Pre-Processing on PLS Quantitative Model of Detecting Cu
in Navel Orange by LIBS].
AB - Cu in navel orange was detected rapidly by laser-induced breakdown spectroscopy
(LIBS) combined with partial least squares (PLS) for quantitative analysis, then
the effect on the detection accuracy of the model with different spectral data
ptetreatment methods was explored. Spectral data for the 52 Gannan navel orange
samples were pretreated by different data smoothing, mean centralized and
standard normal variable transform. Then 319~338 nm wavelength section containing
characteristic spectral lines of Cu was selected to build PLS models, the main
evaluation indexes of models such as regression coefficient (r), root mean square
error of cross validation (RMSECV) and the root mean square error of prediction
(RMSEP) were compared and analyzed. Three indicators of PLS model after 13 points
smoothing and processing of the mean center were found reaching 0. 992 8, 3. 43
and 3. 4 respectively, the average relative error of prediction model is only 5.
55%, and in one word, the quality of calibration and prediction of this model are
the best results. The results show that selecting the appropriate data pre
processing method, the prediction accuracy of PLS quantitative model of fruits
and vegetables detected by LIBS can be improved effectively, providing a new
method for fast and accurate detection of fruits and vegetables by LIBS.
PMID- 26415467
TI - ICP-AES Determination of Mineral Content in Boletus tomentipes Collected from
Different Sites of China.
AB - P, Na, Ca, Cu, Fe, Mg, Zn, As, Cd, Co, Cr and Ni, contents have been examined in
caps and stipes of Boletus tomentipes collected from different sites of Yunnan
province, southwest China. The elements were determined using inductively coupled
plasma atomic emission spectroscopy (ICP-AES) with microwave digestion. P, Ca,
Mg, Fe, Zn and Cu were the most abundant amongst elements determined in Boletus
tomentipes. The caps were richer in P, Mg, Zn and Cd, and the stipes in Ca, Co
and Ni. Cluster analysis showed a difference between Puer (BT7 and BT8) and other
places. The PCA explained about 77% of the total variance, and the minerals
differentiating these places were P (PC1) together with Ca, Cu, Fe, Mg, As and
Ni, Na (PC2) together with Cd, and Zn (PC3). The results of this study imply that
element concentrations of a mushroom are mutative when collected from the
different bedrock soil geochemistry.
PMID- 26415468
TI - [Determination of Total Selenium and Arsenic in Coal by Wet Digestion Hydride
Generation Atomic Fluorescence Spectrometry (HG-AFS)].
AB - In the present work we presented a new method for determination of total Se and
As in coal by electric hot plate-mixed acids-hydride generation atomic
fluorescence spectrometry (HG-AFS), the wet digestion method. The detailed
operation procedures of the new method are as follows: About 0. 05~0. 10 g of
powdered (200 mesh) coal sample was placed in a glass beaker, 10 mL of nitric
acid (HNO3) and 2 mL of perchloric acid (HClO4) were added to the beaker in
sequence, then the beaker was covered with a watching glass and placed in a fume
cupboard standing overnight. The beaker was placed on an electric hot plate (180
degrees C) for sample decomposition the next day. The beaker was moved away from
the electric hot plate when white smoke arose in the beaker, the sample color
turned white or grey and the solution turned clear. Three milliliter of
hydrochloric acid (HCl) solution (6 mol . L-1) was added to the beaker after the
temperature of the beaker returned to room temperature. The beaker was heated on
the electric hot plate again, and then moved away when white smoke started
arising again. One milliliter of HCI was added in the beaker after the
temperature of the beaker returned to room temperature. After that, the digested
sample was transferred to a 25 mL test tube which was filled with ultrapure water
to the tube's full volume. This solution was used for Se determination directly.
Three milliliter of the Se test solution prepared above was transferred to a 15
mL glass test tube, 1 mL of thiourea/ascorbic acid solution (2. 5 g . mL-1) and 1
mL of the concentrated HCl was added to the 15 mL test tube. The test tube was
then filled with ultrapure water to its full volume. The solution was used for As
determination after shaking well and 40 min standing. Finally, Se and As
concentrations in these prepared solutions were measured by using the AFS-9780
instrument (Beijing Haiguang Instrument Co. , LTD, Beijing, China). Two Chinese
Coal Certified Reference Materials (GBW11115 and GBW11117) were tested using this
method, and the recoveries of As were 99. 7%~100. 3% and the relative standard
deviation (RSD) for As and Se were 5. 6%~6. 0% and 11. 1%~13. 5%, respectively.
The limits of detection (LOD) of the method for Se and As determination were 0.
01 and 0. 05 ug . L-1, respectively. These results indicated that this new method
was suitable for Se and As determination in coal, and it had the advantages of
simple operation, high accuracy and reproducibility compared with the Chinese
National Standard method.
PMID- 26415469
TI - [Development of Micro-Spectrometer with a Function of Timely Temperature
Compensation].
AB - Temperature drift will be brought to Micro-Spectrometer used for demodulating the
Varied Line-Space(VLS) grating position sensor on aircraft due to high-low
temperature shock. We successfully made a Micro-Spectrometer, for the VLS grating
position sensor on aircraft, which still have stable output under temperature
shock enviro nment. In order to present a real time temperature compensation
scheme, the effects temperature change has on Micro-Spectrometer are analyzed and
the traditional cross Czerny-Turner (C-T)optical structure is optimized. Both
optical structures are analyzed by optics design software ZEMAX and proved that
comparedwithtraditional cross C-T optical structure, the newone can accomplish
not only smaller spectrum drift but also spectrum drift with better linearity.
Based on the new optical structure. The scheme of using reference wavelength to
accomplish real time temperature compensation was proposed and a Micro-fiber
Spectrometer was successfully manufactured, whith is with Volume of 80 mm X 70
mmX 70 mm, integration time of 8 ~1 000 ms and FullWidthHalfMaximum(FWHM) of 2
nm. Experiments show that the new spectrometer meets the design requirement.
Under high temperature in the range of nearly 60 degrees C, the standard error
of wavelength of this new spectrometer is smaller than 0. 1 nm, and the maximum
error of wavelength is 0. 14 nm, which is much smaller than required 0. 3 nm.
Innovations of this paper are the schemeof real time temperature compensation,
the new cross C-T optical structure and a Micro-fiber Spectrometer based on it.
PMID- 26415470
TI - [Design of a Component and Transmission Imaging Spectrometer].
AB - In the reflection-based imaging spectrometer, multiple reflection(diffraction)
produces stray light and it is difficult to assemble. To address that, a high
performance transmission spectral imaging system based on general optical
components was developed. On the basis of simple structure, the system is easy to
assemble. And it has wide application and low cost compared to traditional
imaging spectrometers. All components in the design can be replaced according to
different application situations, having high degree of freedom. In order to
reduce the influence of stray light, a method based on transmission was
introduced. Two sets of optical systems with different objective lenses were
simulated; the parameters such as distortion, MTF and aberration.were analyzed
and optimized in the ZEMAX software. By comparing the performance of system with
different objective len 25 and 50 mm, it can be concluded that the replacement of
telescope lens has little effect on imaging quality of whole system. An imaging
spectrometer is developed successfully according design parameters. The telescope
lens uses double Gauss structures, which is beneficial to reduce field curvature
and distortion. As the craftsmanship of transmission-type plane diffraction
grating is mature, it can be used without modification and it is easy to
assemble, so it is used as beam-split. component of the imaging spectrometer. In
addition, the real imaging spectrometer was tested for spectral resolution and
distortion. The result demonstrates that the system has good ability in
distortion control, and spectral resolution is 2 nm. These data satisfy the
design requirement, and obtained spectrum of deuterium lamp through calibrated
system are ideal results.
PMID- 26415471
TI - [Design and Optimization of Surface Plasmon Resonance Sensor Based on Side
Polished Single-Mode Fiber].
AB - Fiber-coupling surface Plasmon resonance sensor has attractive advantages of
information transmission such as small volume, anti-electric magnetic field
interference, and online real-time remote detection. In order to improve the
performance of the sensor, the effect of the residual fiber thickness and the
silver film thickness to the sensitivity of the sensor and the depth of the
resonance peaks and full width ar half maximum (FWHM) are analyzed respectively.
The results show that the increasing fiber residual thickness weakens the SPR
phenomenon, and that the increasing silver film thickness widens the resonance
peak, while the sensitivity of the sensor does not change monotonously. Through
the integration of refractive index sensing sensitivity and full width at half
maximum, figure of merit is presented and regarded as the optimized objective.
The optimal design is achieved in the case of the fiber residual thickness for
66. 5 um, and the silver film thickness for 50 nm. The optimized design with the
figure of merit of 98. 67 is expected to be applied in the bio-chemical sensing
and analysis.
PMID- 26415472
TI - [New Implementation Technique of USED Phase Matching for CARS].
AB - Phase matching is one of the key techniques in temperature measuring by coherent
anti-Stokes Raman scattering (CARS). In order to overcome the disadvantages of
large background radiation, inconvenient adjusting and low-usage of Stokes laser
energy in traditional unstable-resonator spatially enhanced detection (USED)
phase matching, new implementation technique of USED CARS phase matching is
researched. A piece of oblique reflector, which is as big as the Stokes spot and
with an angle of 45 degrees, was used to replace the annular reflector in
traditional USED to reflect the Stokes fully. Then, pump laser shines from the
back of the oblique reflector to satisfy USED phase matching with reflected
Stokes. In the new USED CARS phase matching, background radiation caused by
reflecting was weakened for the area of oblique reflector is smaller than that of
annular reflector; Furthermore, oblique reflector can be used as an adjusting
component in experiments which can make beam path adjusting more easier; Finally,
Stokes laser was in high-usage for it was fully reflected by the oblique
reflector. Temperature measuring results on laminar flame suggest that new USED
CARS phase matching has lower standard deviation and it is a more effective phase
matching method.
PMID- 26415474
TI - [A Concept Design of Flat-Field Spectrograph for Wide Wavelength Range].
AB - The radiation spectrum from the plasmas contains a large amount of information of
plasmas. Thus, one of the most effective methods to detecting the plasma
parameters is measure the plasma radiation spectrum. Until now, since the
restriction of the Toshiba mechanically ruled aberration-corrected concave
gratings, the measurable wavelength range of the incidence flat-field grazing
spectrometer in the soft X-ray range are only from 5 to 40 nm. In order to extend
the wavelength rang of grazing incidence flat-field spectrometer, first, a
grazing incidence concave reflection grating ray-trace code is written using
optical path equation. Second, under the same conditions with reference 6, we
compare our numerical results with Harada's results. The results show that our
results agree very well with the results of Harada. The results of comparison
show that our ray-trace code is believable. Finally, the variety of the flat
field curves are detailedly investigated using the ray-trace code with the
different grazing incidence conditions. The results show that the measurable
wavelength range of the incidence flat-field grazing spectrometer are extended to
5~80 nm from the soft X-ray wavelength range of 5~40 nm. This result
theoretically demonstrates the possibility of expanded the traditional band flat
field grazing incidence spectrometer from soft X-ray band to the extreme
ultraviolet (XUV), and also bring a new design ideas for improving the use of
grazing incidence flat field concave grating.
PMID- 26415473
TI - [Searching for WDMS Candidates In SDSS-DR10 With Automatic Method].
AB - The Sloan Digital Sky Survey (SDSS) has released the latest data (DR10) which
covers the first APOGEE spectra. The massive spectra can be used for large sample
research inscluding the structure and evolution of the Galaxy and multi-wave-band
identi cation. In addition, the spectra are also ideal for searching for rare and
special objects like white dwarf main-sequence star (WDMS). WDMS consist of a
white dwarf primary and a low-mass main-sequence (MS) companion which has
positive significance to the study of evolution and parameter of close binaries.
WDMS is generally discovered by repeated imaging of the same area of sky,
measuring light curves for objects or through photometric selection with follow
up observations. These methods require significant manual processing time with
low accuracy and the real-time processing requirements can not be satisfied. In
this paper, an automatic and efficient method for searching for WDMS candidates
is presented. The method Genetic Algorithm (GA) is applied in the newly released
SDSS-DR10 spectra. A total number of 4 140 WDMS candidates are selected by the
method and 24 of them are new discoveries which prove that our approach of
finding special celestial bodies in massive spectra data is feasible. In
addition, this method is also applicable to mining other special celestial
objects in sky survey telescope data. We report the identfication of 24 new WDMS
with spectra. A compendium of positions, mjd, plate and fiberid of these new
discoveries is presented which enrich the spectral library and will be useful to
the research of binary evolution models.
PMID- 26415475
TI - [The Stability and Measuring Technology of the Maximum Optical Path Difference of
Photo-Elastic Modulator Interferograms].
AB - In order to improve the accuracy and stability of the rebuilt spectrums, it is
necessary that stability analysis and nicety measuring of the maximum optical
path difference of interferograms in the photo-elastic modulator Fourier
transform spectrometers(PEM-FTS). The maximum optical difference of
interferograms is uncertain parameter, and it is relate to the resonant state,
characteristic of frequency-thermal drift and driving voltage of PEM. Therefore,
based on the principle of photo-elastic modulator Fourier transform
interferometer, the model of the freguency-thermal drift is built, and the
variety of the maximum optical path difference is analyzed; A measuring method of
the maximum optical path difference is put forward, which is zero-crossing
counting of laser's interference signal when the driving signal of PEM is as the
standard. In the method the dual channel high-speed comparator and FPGA are used
to transform sine wave to square wave, to realize zero-crossing trigger counting
and errors compensation. On the condition that the 670. 8 nm laser is as the
power source to produce the reference interferograms by the PEM interferometer,
the 77. 471 um maximum optical path difference could be measured by the zero
crossing counting the measuring errors is less than 0. 167 nm, the rebuilt
spectral peak wavelength errors of the infrared blackbody is less than 2 nm. the
result is content with PEM-FTS.
PMID- 26415476
TI - [Research on Anti-Camouflaged Target System Based on Spectral Detection and Image
Recognition].
AB - To be able to quickly and efficiently identify Enemy camouflaged maneuvering
targets in the wild environment, target recognition system was designed based on
spectral detection technology and video target recognition method. System was
composed of the visible light image acquisition module and static interferometer
module. The system used image recognition technology to obtain two dimensional
video images of measurement region, and through spectrum detection technology to
identify targets. Ultimately, measured target was rebuilt on the corresponding
position in the image, so the visual target recognition was realized. After the
theoretical derivation, identifiable target function formula of the system was
obtained, and based on the functional relationship to complete the quantitative
experiments for target recognition. In the experiments, maneuvering target in the
battlefield environment was simulated by a car. At different distances, the
background was respectively selected to detect a flat wasteland, bushes and
abandoned buildings. Obvious target, coated camouflage target and covered
disguises target was respectively spectrum detection. Experimental results show
that spectrum detection technology can overcome the shortcomings of unrecognized
the camouflaged target by traditional image target recognition method. Testing
background had some influence on spectrum detection results, and the continuity
of the background was conducive to target recognition. Covered disguises target
was the hardest to identify in various camouflage mode. As the distance between
the target and the system increases, signal to noise ratio of the system was
reduced. In summary, the system can achieve effective recognition of camouflaged
targets to meet the design requirements.
PMID- 26415477
TI - [Spectral Smoothing with Adaptive Multiscale Window Average].
AB - In order to smooth the spectra automatically and reliably, a spectral smoothing
algorithm with adaptive multiscale window average (AWMA) is demonstrated. In this
method, different positions of the spectra are smoothed by windows of different
width, and the width of the windows will directly affect smoothing. The window
with inappropriate width may cause excessive denoising (peak distortion or loss)
or inadequate denoising (the flat region of the spectra still contains a lot of
noise). So, how to get the right width of the window is the key of spectral
smoothing. The algorithm optimized the width of windows by an iterative method,
and verified whether the width is the best according to statistical Z-test. In
order to increase the reliability of the algorithm, a comprehensive comparison of
the thresholds of hypothesis according to simulation data of different SNR was
performed. When the threshold is set to 1. 1, the denoising effect can be the
best. In this work, the AMWA algorithm was tested by simulated spectra and real
syectra, and it can automatically adapt to different spectral shape and different
noise intensity. A comprehensive comparison of AMWA smoothing, Savitzky-Golay
smoothing and moving average smoothing was performed in this paper, and the AMWA
algorithm is better than the other two algorithms. Results show that the AMWA
algorithm not only has better denoising effect, but also has higher accuracy and
fidelity. This method has achieved great effect not only to simulated spectra but
also to real spectra.
PMID- 26415478
TI - A Model-Based Temperature-Prediction Method by Temperature-Induced Spectral
Variation and Correction of the Temperature Effect.
AB - In the present paper, a new model-based method was proposed for temperature
prediction and correction. First, a temperature prediction model was obtained
from training samples; then, the temperature of test samples were predicted; and
finally, the correction model was used to reduce the nonlinear effects of spectra
from temperature variations. Two experiments were used to verify the proposed
method, including a water-ethanol mixture experiment and a ternary mixture
experiment. The results show that, compared with classic method such as
continuous piecewise direct standardization (CPDS), our method is efficient for
temperature correction. Furthermore, the temperatures of test samples are not
necessary in the proposed method, making it easier to use in real applications.
PMID- 26415479
TI - Craig Richmond. the value of transparency in improving patient education.
PMID- 26415480
TI - Developing the metrics for payment reform.
PMID- 26415481
TI - Soft-leadership competencies for today's healthcare finance executives.
AB - With the healthcare industry changing rapidly, organizations seek finance leaders
who have skills that go beyond traditional expertise in revenue and expenses.
These additional competencies fall under the heading of soft-leadership skills
and include the ability to be strategy-oriented, agile, passionate,
inspirational, influential, communicative, dependable, driven, integrative, and
engaged. Networking, participation in a mentoring program, and continuing
education provide avenues for finance leaders to develop these sorts of skills.
PMID- 26415483
TI - Infusing the capital review process with rigor and discipline.
AB - Intermountain Healthcare gleaned four key insights from inside and outside the
industry when reviewing best practices in capital decision making: Evidence-based
decision making and disciplined analysis are as critical in healthcare finance as
in any other industry. Comparing various scenarios under value-based payment
allows for better modeling than does performing traditional, volume-based pro
formas. Reviewing large capital projects at a granular level helps identify
opportunities to add or subtract services. A comprehensive look-back process
identifies lessons learned from approved projects-and helps ensure that proposals
are defensible.
PMID- 26415482
TI - Lost opportunity. Fairly assigning value to physician administrative services.
AB - The Resource-Based Relative Value System sets values for physician services that
can be used to estimate the value of time spent on administrative tasks. This
methodology assigns an appropriate place-of-service qualifier and the appropriate
percentage of Medicare rates to the time being spent on administrative tasks. A
variation of this methodology allows for a rate to be determined for an entire
physician group or specialty.
PMID- 26415484
TI - 'Capital ideas' for health care in 2015.
AB - Key factors in planning for healthcare financing in 2015 include: New rules
related to municipal advisors. Long-term interest rates and the cost of
traditional versus synthetic fixed-rate debt. Ways to use interest-rate swaps to
take advantage of synthetic fixed-rate debt. Lesser-known structures that may
make variable-rate financing advantageous.
PMID- 26415485
TI - Getting the right asset mix.
AB - To accurately measure service costs associated with medical equipment, hospitals
should undertake a four-step process: Form a core project team and define the
project's scope. Collect data. Employ forensic accounting to ascertain the actual
service costs for clinical equipment. Analyze key metrics to identify savings
opportunities
PMID- 26415486
TI - Demystifying patient price estimates. The advantages of transparency.
AB - With the increase of high-deductible health plans, more consumers want to know
the cost of their health care before they purchase services. A healthcare
organization should formulate transparent price policies that: Fit with its
intentions, processes, and goals. Ensure consumers are thoroughly educated about
their financial responsibilities. Include the use of consumer pricing tools that
help patients feel like empowered consumers. Reflect an enterprisewide culture of
transparency.
PMID- 26415487
TI - Elevating revenue cycle performance across the enterprise.
AB - Healthcare organizations can effectively bridge the revenue cycle gap between
hospitals and physician practices by positioning themselves strategically for
integration in six ways: Making sure they are culturally ready. Installing
leaders who are comfortable with both hospital and physician operations.
Developing a clear plan for the initiative. Investing in integrated technology.
Using consistent data definitions. Pursuing improvements that yield the best
possible results.
PMID- 26415489
TI - The value proposition in action.
PMID- 26415488
TI - Patient throughput collaborative yields positive results for New Jersey
hospitals.
AB - Collecting and analyzing data was a key step in a process improvement initiative
undertaken by several hospitals in New Jersey. The hospitals found that patient
flow problems commonly stemmed from uneven use of operating rooms and unenforced
admission/discharge policies on inpatient units. Shared solutions included
improving staff communication and enforcing admission/discharge policies.
PMID- 26415490
TI - ACOs: from unicorns to pacesetters in four years.
PMID- 26415491
TI - Comparative performance of hospitals based on credit ratings.
PMID- 26415492
TI - Actinomyces gerencseriae hip prosthesis infection: a case report.
AB - INTRODUCTION: Actinomyces bacteria are part of the human oropharyngeal
microbiota. They have been associated with abdominal, cervicofacial and thoracic
infections and a few cases of joint infections have also been described. In
particular, Actinomyces gerencseriae, formerly described as Actinomyces israelii
serovar II, has rarely been associated with human infections, mostly involving
cervicofacial lesions and periodontal diseases. Here, we report one case of hip
prosthesis infection due to A. gerencseriae. CASE PRESENTATION: A 72-year-old
Caucasian male developed an inflammatory collection on the outside of the right
thigh where a hip prosthesis had been implanted for 11 years. Culturing a fluid
sample from the collection puncture found Staphylococcus hominis and a Gram
positive bacillus unidentified by matrix-assisted laser desorption ionization
time-of-flight mass-spectrometry (MALDI-TOF). Sequencing the 16S rRNA gene
amplified from both the specimen and the isolate identified A. gerencseriae.
Treatment adjusted with amoxicillin and trimethropim-sulfamethoxazole cured the
infection. CONCLUSION: The recently described A. gerencseriae has rarely been
involved in human infections. We report the first case of A. gerencseriae joint
infection in a hip prosthesis.
PMID- 26415493
TI - Changing trends in hospitalization rates associated with psychosis: Spain, 1980
2009.
AB - PURPOSE: To analyze the prevalence of hospitalization attributable to psychosis
in Spain over the last three decades. METHODS: Longitudinal analysis (1980-2009)
of age-adjusted hospital discharges rates associated with psychosis (ICD9 290-8)
in all Spanish hospitals. DATA SOURCE: Spanish Hospital Morbidity Survey.
RESULTS: The hospitalization rate associated with psychotic episodes had been
gradually increasing since 1980 until 2004; an abrupt turnaround observed in 2004
marks the beginning of a steady decline in the rate. The turning point described
is not observed for each of the psychotic diagnoses separately analyzed. However,
it is clearly seen when data are grouped in diagnosis-related groups (organic
psychosis, functional psychosis and substance-induced psychosis) since the time
course of the diseases within the major diagnostic groups are interrelated as
evidenced by shared turning points which collectively display a common time
course pattern. Main hospital indicators and antipsychotic drug prescriptions
were analyzed for any possible turning point in mid-2000s. Psychiatric hospital
beds and length of stays remained stable by 2004; the hospitalizations associated
with non-psychotic psychiatric pathologies show no turning point in 2004.
However, an abrupt change on antipsychotic drug prescriptions is precisely
observed in 2004. CONCLUSIONS: After decades of linear growth, hospitalizations
for psychotic patients begin to decline in 2004, coinciding with the start of
last generation atypical antipsychotic drug consumption in Spain. Some of the
psychotic diagnostic rates evolve in an interrelated manner which calls into
question the diagnosis and nosological boundaries between some of these
pathologies.
PMID- 26415494
TI - Clustering reveals limits of parameter identifiability in multi-parameter models
of biochemical dynamics.
AB - BACKGROUND: Compared to engineering or physics problems, dynamical models in
quantitative biology typically depend on a relatively large number of parameters.
Progress in developing mathematics to manipulate such multi-parameter models and
so enable their efficient interplay with experiments has been slow. Existing
solutions are significantly limited by model size. RESULTS: In order to simplify
analysis of multi-parameter models a method for clustering of model parameters is
proposed. It is based on a derived statistically meaningful measure of similarity
between groups of parameters. The measure quantifies to what extend changes in
values of some parameters can be compensated by changes in values of other
parameters. The proposed methodology provides a natural mathematical language to
precisely communicate and visualise effects resulting from compensatory changes
in values of parameters. As a results, a relevant insight into identifiability
analysis and experimental planning can be obtained. Analysis of NF-kappaB and
MAPK pathway models shows that highly compensative parameters constitute clusters
consistent with the network topology. The method applied to examine an
exceptionally rich set of published experiments on the NF-kappaB dynamics reveals
that the experiments jointly ensure identifiability of only 60% of model
parameters. The method indicates which further experiments should be performed in
order to increase the number of identifiable parameters. CONCLUSIONS: We
currently lack methods that simplify broadly understood analysis of multi
parameter models. The introduced tools depict mutually compensative effects
between parameters to provide insight regarding role of individual parameters,
identifiability and experimental design. The method can also find applications in
related methodological areas of model simplification and parameters estimation.
PMID- 26415495
TI - Diagnostic performance of measuring antibodies to the glycopeptidolipid core
antigen specific to Mycobacterium avium complex in patients with rheumatoid
arthritis: results from a cross-sectional observational study.
AB - INTRODUCTION: The aim of this study was to investigate the diagnostic performance
of measuring antibodies to the glycopeptidolipid (GPL) core antigen specific to
Mycobacterium avium complex (MAC) in patients with rheumatoid arthritis (RA).
METHODS: We cross-sectionally investigated anti-GPL antibodies and radiographs of
396 patients with RA. A diagnosis of MAC pulmonary disease (MAC-PD) was made
according to the criteria by the American Thoracic Society and the Infectious
Diseases Society of America. Serum immunoglobulin A antibodies to MAC-specific
GPL core antigen were measured by an enzyme immunoassay. All patients with RA
with abnormal shadows on chest x-rays underwent chest computed tomography (CT).
Bronchoscopy was performed on patients with negative cultures for MAC by
expectorated sputum and positive CT findings compatible with MAC-PD. RESULTS: Ten
patients were newly diagnosed with MAC-PD. Eight individuals who already had
diagnoses of MAC-PD at the time of enrollment and nineteen who had negative
expectorated sputum cultures for MAC and positive CT images compatible with MAC
PD and who refused bronchoscopy were excluded from the following analysis. Anti
GPL antibodies were detected in 12 of 369 patients. Eight of the ten patients
with MAC-PD and 4 of 359 patients without MAC-PD tested positive for the anti-GPL
antibodies. The specificity and sensitivity were 99 % and 80 %, respectively.
Positive and negative predictive values were 67 %, and 97 %, respectively. When
we analyzed diagnostic performance of the antibodies in 57 patients with RA who
had abnormal shadows on chest x-rays, the positive and negative predictive values
were 100 %, and 96 %, respectively. Twelve patients underwent bronchoscopy.
Bronchoalveolar lavage fluid (BALF) samples from six patients were positive for
MAC, and BALF samples from the remainder were negative. Anti-GPL antibodies were
detected in the sera of all six patients with positive results for MAC by BALF
sampling, whereas the antibodies were not detected in the sera from the remainder
with negative results for MAC by BALF sampling. CONCLUSIONS: The measurement of
anti-GPL antibodies is useful as a supplementary diagnostic tool for MAC-PD in
patients with RA and may provide a new strategy, in combination with chest x-ray
and CT, for differentiating MAC-PD from other pulmonary comorbidities in patients
with RA.
PMID- 26415496
TI - Lifetime co-occurrence of violence victimisation and symptoms of psychological
ill health: a cross-sectional study of Swedish male and female clinical and
population samples.
AB - BACKGROUND: Lifetime co-occurrence of violence victimisation is common. A large
proportion of victims report being exposed to multiple forms of violence
(physical, sexual, emotional violence) and/or violence by multiple kinds of
perpetrators (family members, intimate partners, acquaintances/strangers). Yet
much research focuses on only one kind of victimisation. The aim of this study
was to investigate the association between symptoms of psychological ill health,
and A) exposure to multiple forms of violence, and B) violence by multiple
perpetrators. METHOD: Secondary analysis of cross-sectional data previously
collected for prevalence studies on interpersonal violence in Sweden was used.
Respondents were recruited at hospital clinics (women n = 2439, men n = 1767) and
at random from the general population (women n = 1168, men n = 2924). Multinomial
regression analysis was used to estimate associations between exposure to
violence and symptoms of psychological ill health. RESULTS: Among both men and
women and in both clinical and population samples, exposure to multiple forms of
violence as well as violence by multiple perpetrators were more strongly
associated with symptoms of psychological ill health than reporting one form of
violence or violence by one perpetrator. For example, in the female population
sample, victims reporting all three forms of violence were four times more likely
to report many symptoms of psychological ill health compared to those reporting
only one form of violence (adj OR: 3.8, 95 % CI 1.6-8.8). In the male clinical
sample, victims reporting two or three kind of perpetrators were three times more
likely to report many symptoms of psychological ill health than those reporting
violence by one perpetrator (adj OR 3.3 95 % CI 1.9-5.9). DISCUSSION: The strong
association found between lifetime co-occurrence of violence victimisation and
symptoms of psychological ill-health is important to consider in both research
and clinic work. If only the effect of one form of violence or violence by one
kind of perpetrator is considered this may lead to a misinterpretation of the
association between violence and psychological ill health. When the effect of
unmeasured traumata is ignored, the full burden of violence experienced by
victims may be underestimated. CONCLUSION: Different kinds of victimisation can
work interactively, making exposure to multiple forms of violence as well as
violence by multiple perpetrators more strongly associated with symptoms of
psychological ill health than any one kind of victimisation alone.
PMID- 26415497
TI - Animal models for photodynamic therapy (PDT).
AB - Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs),
which absorb visible light to give the excited singlet state, followed by the
long-lived triplet state that can undergo photochemistry. In the presence of
ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and
hydroxyl radicals are formed that are able to kill cancer cells, inactivate
microbial pathogens and destroy unwanted tissue. Although there are already
several clinically approved PSs for various disease indications, many studies
around the world are using animal models to investigate the further utility of
PDT. The present review will cover the main groups of animal models that have
been described in the literature. Cancer comprises the single biggest group of
models including syngeneic mouse/rat tumours that can either be subcutaneous or
orthotopic and allow the study of anti-tumour immune response; human tumours that
need to be implanted in immunosuppressed hosts; carcinogen-induced tumours; and
mice that have been genetically engineered to develop cancer (often by pathways
similar to those in patients). Infections are the second biggest class of animal
models and the anatomical sites include wounds, burns, oral cavity, ears, eyes,
nose etc. Responsible pathogens can include Gram-positive and Gram-negative
bacteria, fungi, viruses and parasites. A smaller and diverse group of
miscellaneous animal models have been reported that allow PDT to be tested in
ophthalmology, atherosclerosis, atrial fibrillation, dermatology and wound
healing. Successful studies using animal models of PDT are blazing the trail for
tomorrow's clinical approvals.
PMID- 26415498
TI - Replication study of the vitamin D receptor (VDR) genotype association with
skeletal muscle traits and sarcopenia.
AB - Polymorphisms in the vitamin D receptor (VDR) gene are some of the most studied
in relation to skeletal muscle traits and significant associations have been
observed by multiple groups. One such paper by our group provided the first
evidence of a genetic association with sarcopenia in men, but that finding has
yet to be replicated in an independent cohort. In the present study, we examined
multiple VDR polymorphisms in relation to skeletal muscle traits and sarcopenia
in 864 men and women across the adult age span. In addition to VDR genotypes and
haplotypes, measurements of skeletal muscle strength and fat-free mass (FFM) were
determined in all subjects and a measure of sarcopenia was calculated. We
observed significant associations between Fok1 and Bsm1 genotypes and skeletal
muscle strength in men and women, though these associations were modest and no
significant associations were observed for these polymorphisms and muscle mass
traits nor for Bsm1-Taq1 haplotype with muscle strength. Fok1 FF genotype was
associated with an increased the risk of sarcopenia in older women compared to f
allele carriers (1.3-fold higher risk). These results support previous findings
that VDR genetic variation appears to impact skeletal muscle strength and risk
for sarcopenia but the influence is modest.
PMID- 26415499
TI - Expression of calpain-like proteins and effects of calpain inhibitors on the
growth rate of Angomonas deanei wild type and aposymbiotic strains.
AB - BACKGROUND: Angomonas deanei is a trypanosomatid parasite of insects that has a
bacterial endosymbiont, which supplies amino acids and other nutrients to its
host. Bacterium loss induced by antibiotic treatment of the protozoan leads to an
aposymbiotic strain with increased need for amino acids and results in increased
production of extracellular peptidases. In this work, a more detailed examination
of A. deanei was conducted to determine the effects of endosymbiont loss on the
host calpain-like proteins (CALPs), followed by testing of different calpain
inhibitors on parasite proliferation. RESULTS: Western blotting showed the
presence of different protein bands reactive to antibodies against calpain from
Drosophila melanogaster (anti-Dm-calpain), lobster calpain (anti-CDPIIb) and
cytoskeleton-associated calpain from Trypanosoma brucei (anti-CAP5.5), suggesting
a possible modulation of CALPs influenced by the endosymbiont. In the cell-free
culture supernatant of A. deanei wild type and aposymbiotic strains, a protein of
80 kDa cross-reacted with the anti-Dm-calpain antibody; however, no cross
reactivity was found with anti-CAP5.5 and anti-CDPIIb antibodies. A search in A.
deanei genome for homologues of D. melanogaster calpain, T. brucei CAP5.5 and
lobster CDPIIb calpain revealed the presence of hits with at least one calpain
conserved domain and also with theoretical molecular mass consistent with the
recognition by each antibody. No significant hit was observed in the endosymbiont
genome, indicating that calpain molecules might be absent from the symbiont. Flow
cytometry analysis of cells treated with the anti-calpain antibodies showed that
a larger amount of reactive epitopes was located intracellularly. The reversible
calpain inhibitor MDL28170 displayed a much higher efficacy in diminishing the
growth of both strains compared to the non-competitive calpain inhibitor
PD150606, while the irreversible calpain inhibitor V only marginally diminished
the proliferation. CONCLUSIONS: Altogether, these results indicate that distinct
calpain-like molecules are expressed by A. deanei, with a possible modulation in
the expression influenced by the endosymbiont. In addition, treatment with
MDL28170 affects the growth rate of both strains, as previously determined in the
human pathogenic species Leishmania amazonensis and Trypanosoma cruzi, with whom
A. deanei shares immunological and biochemical relationships.
PMID- 26415500
TI - A comparison of confidence interval methods for the intraclass correlation
coefficient in community-based cluster randomization trials with a binary
outcome.
AB - BACKGROUND: Many investigators rely on previously published point estimates of
the intraclass correlation coefficient rather than on their associated confidence
intervals to determine the required size of a newly planned cluster randomized
trial. Although confidence interval methods for the intraclass correlation
coefficient that can be applied to community-based trials have been developed for
a continuous outcome variable, fewer methods exist for a binary outcome variable.
The aim of this study is to evaluate confidence interval methods for the
intraclass correlation coefficient applied to binary outcomes in community
intervention trials enrolling a small number of large clusters. Existing methods
for confidence interval construction are examined and compared to a new ad hoc
approach based on dividing clusters into a large number of smaller sub-clusters
and subsequently applying existing methods to the resulting data. METHODS: Monte
Carlo simulation is used to assess the width and coverage of confidence intervals
for the intraclass correlation coefficient based on Smith's large sample
approximation of the standard error of the one-way analysis of variance
estimator, an inverted modified Wald test for the Fleiss-Cuzick estimator, and
intervals constructed using a bootstrap-t applied to a variance-stabilizing
transformation of the intraclass correlation coefficient estimate. In addition, a
new approach is applied in which clusters are randomly divided into a large
number of smaller sub-clusters with the same methods applied to these data (with
the exception of the bootstrap-t interval, which assumes large cluster sizes).
These methods are also applied to a cluster randomized trial on adolescent
tobacco use for illustration. RESULTS: When applied to a binary outcome variable
in a small number of large clusters, existing confidence interval methods for the
intraclass correlation coefficient provide poor coverage. However, confidence
intervals constructed using the new approach combined with Smith's method provide
nominal or close to nominal coverage when the intraclass correlation coefficient
is small (<0.05), as is the case in most community intervention trials.
CONCLUSION: This study concludes that when a binary outcome variable is measured
in a small number of large clusters, confidence intervals for the intraclass
correlation coefficient may be constructed by dividing existing clusters into sub
clusters (e.g. groups of 5) and using Smith's method. The resulting confidence
intervals provide nominal or close to nominal coverage across a wide range of
parameters when the intraclass correlation coefficient is small (<0.05).
Application of this method should provide investigators with a better
understanding of the uncertainty associated with a point estimator of the
intraclass correlation coefficient used for determining the sample size needed
for a newly designed community-based trial.
PMID- 26415501
TI - A cell-based model system links chromothripsis with hyperploidy.
AB - A remarkable observation emerging from recent cancer genome analyses is the
identification of chromothripsis as a one-off genomic catastrophe, resulting in
massive somatic DNA structural rearrangements (SRs). Largely due to lack of
suitable model systems, the mechanistic basis of chromothripsis has remained
elusive. We developed an integrative method termed "complex alterations after
selection and transformation (CAST)," enabling efficient in vitro generation of
complex DNA rearrangements including chromothripsis, using cell perturbations
coupled with a strong selection barrier followed by massively parallel
sequencing. We employed this methodology to characterize catastrophic SR
formation processes, their temporal sequence, and their impact on gene expression
and cell division. Our in vitro system uncovered a propensity of chromothripsis
to occur in cells with damaged telomeres, and in particular in hyperploid cells.
Analysis of primary medulloblastoma cancer genomes verified the link between
hyperploidy and chromothripsis in vivo. CAST provides the foundation for
mechanistic dissection of complex DNA rearrangement processes.
PMID- 26415502
TI - Differentially expressed microRNAs in bone marrow mesenchymal stem cell-derived
microvesicles in young and older rats and their effect on tumor growth factor
beta1-mediated epithelial-mesenchymal transition in HK2 cells.
AB - INTRODUCTION: The prevalence of renal fibrosis is higher in older than in younger
individuals. Through paracrine activity, bone marrow mesenchymal stem cell
derived microvesicles (BM-MSC-MVs) influence the process of renal fibrosis.
Differences in microRNA (miRNA) expression of BM-MSC-MVs that correlate with the
age of the subjects and the correlation between miRNA expression and the process
of renal fibrosis have not been established. The present study aimed to analyze
differences in miRNA expression of BM-MSC-MVs between young or older rats and its
influence on tumor growth factor-beta 1 (TGF-beta1)-mediated epithelial
mesenchymal transition (EMT) of HK2 cells to explore the causes of renal fibrosis
in aged tissues. METHODS: miRCURY LNA Array (version 18.0) was used to identify
differentially expressed miRNAs in BM-MSC-MVs of 3- and 24-month-old Fisher344
rats. Reverse transcription-polymerase chain reaction was used to verify miRNA
levels in BM-MSC-MVs and in the serum of rats. A TGF-beta1-mediated EMT model was
used to study the effects of BM-MSC-MVs and differentially expressed miRNAs on
EMT. RESULTS: BM-MSCs from older rats showed more severe aging phenotypes
compared with those of young rats. In addition, the growth rate and cell
migration of BM-MSCs derived from older rats were significantly reduced. In
secreted BM-MSC-MVs, the expression of miR-344a, miR-133b-3p, miR-294, miR-423
3p, and miR-872-3p was significantly downregulated in older rats than in younger
rats (P < 0.05), and the serum level of these miRNAs exhibited the same patterns.
Intervention using BM-MSC-MVs resulted in the weakening of TGF-beta1-mediated EMT
in the aged rats. MiR-344a, miR-133b-3p, and miR-294 affected TGF-beta1-mediated
EMT in HK2 cells. Among these, miR-133b-3p and miR-294 significantly inhibited
TGF-beta1-mediated EMT in HK2 cells (P < 0.05). CONCLUSIONS: In older rats, the
inhibitory effect of BM-MSC-MVs on TGF-beta1-mediated HK2 cell EMT was weaker
than that observed in younger rats. In addition, miR-133b-3p and miR-294, which
were downregulated in BM-MSC-MVs of older rats, remarkably inhibited TGF-beta1
mediated EMT in HK2 cells, suggesting that these may play a role in the fibrosis
of aging renal tissues.
PMID- 26415503
TI - Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary
vasoconstriction in endotoxemic mice.
AB - BACKGROUND: Inhaled carbon monoxide (CO) appears to have beneficial effects on
endotoxemia-induced impairment of hypoxic pulmonary vasoconstriction (HPV). This
study aims to specify correct timing of CO application, it's biochemical
mechanisms and effects on inflammatory reactions. METHODS: Mice (C57BL/6; n = 86)
received lipopolysaccharide (LPS, 30 mg/kg) intraperitoneally and subsequently
breathed 50 ppm CO continuously during defined intervals of 3, 6, 12 or 18 h. Two
control groups received saline intraperitoneally and additionally either air or
CO, and one control group received LPS but breathed air only. In an isolated lung
perfusion model vasoconstrictor response to hypoxia (FiO2 = 0.01) was quantified
by measurements of pulmonary artery pressure. Pulmonary capillary pressure was
estimated by double occlusion technique. Further, inflammatory plasma cytokines
and lung tissue mRNA of nitric-oxide-synthase-2 (NOS-2) and heme oxygenase-1 (HO
1) were measured. RESULTS: HPV was impaired after LPS-challenge (p < 0.01). CO
exposure restored HPV-responsiveness if administered continuously for full 18 h,
for the first 6 h and if given in the interval between the 3(rd) and 6(th) hour
after LPS-challenge (p < 0.05). Preserved HPV was attributable to recovered
arterial resistance and associated with significant reduction in NOS-2 mRNA when
compared to controls (p < 0.05). We found no effects on inflammatory plasma
cytokines. CONCLUSION: Low-dose CO prevented LPS-induced impairment of HPV in a
time-dependent manner, associated with a decreased NOS-2 expression.
PMID- 26415505
TI - "Poppy" yeast.
PMID- 26415504
TI - AIF inhibits tumor metastasis by protecting PTEN from oxidation.
AB - Apoptosis-inducing factor (AIF) exerts dual roles on cell death and survival, but
its substrates as a putative oxidoreductase and roles in tumorigenesis remain
elusive. Here, we report that AIF physically interacts with and inhibits the
oxidation of phosphatase and tensin homolog on chromosome ten (PTEN), a tumor
suppressor susceptible for oxidation-mediated inactivation. More intriguingly, we
also identify PTEN as a mitochondrial protein and the ectopic expression of
mitochondrial targeting sequence-carrying PTEN almost completely inhibits Akt
phosphorylation in PTEN-deficient cells. AIF knockdown causes oxidation-mediated
inactivation of the lipid phosphatase activity of PTEN, with ensuing activation
of Akt kinase, phosphorylation of the Akt substrate GSK-3beta, and activation of
beta-catenin signaling in cancer cells. Through its effect on beta-catenin
signaling, AIF inhibits epithelial-mesenchymal transition (EMT) and metastasis of
cancer cells in vitro and in orthotopically implanted xenografts. Accordingly,
the expression of AIF is correlated with the survival of human patients with
cancers of multiple origins. These results identify PTEN as the substrate of AIF
oxidoreductase and reveal a novel function for AIF in controlling tumor
metastasis.
PMID- 26415506
TI - ABCG2 impairs the activity of the aurora kinase inhibitor tozasertib but not of
alisertib.
AB - BACKGROUND: Recently, we have shown that the ATP-binding cassette (ABC)
transporter ABCB1 interferes with the anti-cancer activity of the pan-aurora
kinase inhibitor tozasertib (VX680, MK-0457) but not of the aurora kinase A and B
inhibitor alisertib (MLN8237). Preliminary data had suggested tozasertib also to
be a substrate of the ABC transporter ABCG2, another ABC transporter potentially
involved in cancer cell drug resistance. Here, we studied the effect of ABCG2 on
the activity of tozasertib and alisertib. RESULTS: The tozasertib concentration
that reduces cell viability by 50% (IC50) was dramatically increased in ABCG2
transduced UKF-NB-3(ABCG2) cells (48.8-fold) compared to UKF-NB-3 cells and
vector-transduced control cells. The ABCG2 inhibitor WK-X-34 reduced tozasertib
IC50 to the level of non-ABCG2-expressing UKF-NB-3 cells. Furthermore, ABCG2
depletion from UKF-NB-3(ABCG2) cells using another lentiviral vector expressing
an shRNA against the bicistronic mRNA of ABCG2 and eGFP largely re-sensitised
these cells to tozasertib. In contrast, alisertib activity was not affected by
ABCG2 expression. CONCLUSIONS: Tozasertib but not alisertib activity is affected
by ABCG2 expression. This should be considered within the design and analysis of
experiments and clinical trials investigating these compounds.
PMID- 26415507
TI - Individual and community level determinants of childhood full immunization in
Ethiopia: a multilevel analysis.
AB - BACKGROUND: Expanded program on immunization is one of the most successful and
cost effective public health interventions that protect children against vaccine
preventable diseases. The full childhood immunization coverage in many parts of
Ethiopia is far from optimal. Hence, the main objective of this study was to
assess factors associated with childhood full immunization in Ethiopia. METHODS:
The data source for this study was the 2011 Ethiopian Demographic and Health
Survey. Multilevel regression analysis techniques were used to conduct the
analysis. Accordingly a two level multilevel regression analysis model was built
with individuals (level 1) nested with in communities (level 2). RESULTS: A total
of 4983 children aged 12-59 months nested within 520 clusters were included in
the analysis. According to the analysis results, in the year 2011, 26 % of
children less than 5 years old were fully immunized in Ethiopia. Being born at
health institutions, higher level of maternal education, media exposure, region
of residence and residing in communities possessing higher maternal antenatal
care services utilization were positively associated with childhood full
immunization. In contrary to this, the number children aged less than 5 years in
the household was negatively associated with childhood full immunization. The
random effect results indicated that 21 % of the variation among the communities
was due to community level factors. CONCLUSIONS: It was found that various
individual and contextual factors were associated with childhood full
immunization. In addition, significant community level variation remains after
having controlled individual and community level factors which is an indicative
of a need for further research on community level factors. Hence, utilizing
multilevel modeling in determining the effect of both individual and contextual
level factors simultaneously had brought an important output which may help
planners, policy and decision makers to emphasize on both individuals and
communities in which they live.
PMID- 26415508
TI - Differential replicative ability of clinical dengue virus isolates in an
immunocompetent C57BL/6 mouse model.
AB - BACKGROUND: Several experimental animal models have been used to study the
pathogenesis of dengue disease; however, most of the studies used laboratory
adapted viruses, which lack the virulence of viruses circulating in humans. The
aim of this study was to analyze the ability of clinical Dengue virus (DENV)
isolates (D2/BR/RP/RMB/09 and D3/BR/SL3/02) to infect immunocompetent C57BL/6
mice. METHODS: Two strategies of intraperitoneal infection, which were based on
the concept of the antibody dependent enhancement phenomenon, were used. In one
strategy, the animals were inoculated with macrophages infected in vitro with
dengue viruses, which were incubated with enhancing antibodies, and in the other
strategy, the animals were inoculated with a complex of enhancing antibodies and
dengue viruses. RESULTS: The D3/BR/SL3/08 isolate showed a higher ability of
infection (virus RNA was more frequently detected in the serum and in several
organs) in the experimental model compared to both the D2/BR/RP/RMB/2009 isolate
and a laboratory adapted DENV-1 strain (Mochizuki strain), regardless of the
infection strategy used. The main features of the D3/BR/SL3/08 isolate were its
neuroinvasiveness and the induction of an extended period of viremia. Enhancing
antibodies did not influence on the infection of animals when macrophages were
used, but the level of viremia was increased when they were used as a complex
with a D3/BR/SL3/02 isolate. DISCUSSION: We showed that DENV isolates could
infect immunocompetent C57BL/6 mice, which have has been previously used to study
some aspect of dengue disease when infected with laboratory adapted strains. DENV
genome was detected in the same organs found in humans when autopsy and biopsy
samples were analyzed, showing that C57BL/6 mice reproduce some aspects of the
DENV tropism observed in humans. The main difference observed between the
D3/BR/SL3/02 and D2/BR/RP/RMB/2009 clinical isolates was the neuroinvasive
ability of the first one. Neuroinvasiveness has been described in some DENV
infected cases and is common for other members of the Flavivirus genus.
CONCLUSIONS: These results suggest that C57BL/6 mice can be used as an
experimental model to evaluate virulence differences among DENV clinical
isolates.
PMID- 26415509
TI - Gloriosa superba poisoning mimicking an acute infection- a case report.
AB - BACKGROUND: Gloriosa superba (GSb) is a highly poisonous plant and its toxicity
is due to anti-mitotic effects of constituents such as colchicine and gloriosine
on rapidly proliferating cells. Poisoning is known to cause very rapid and severe
clinical manifestations due gastro intestinal, neurological, cardiac and bone
marrow toxicity. CASE PRESENTATION: A young male presented with an acute onset
febrile illness associated with diarrhoea, confusion, haematuria and aggressive
behavior of 4 days duration. He developed subconjunctival haemorrhages, bleeding
gums, neck stiffness, bilateral papilloedema, tender hepatomegaly and features
suggestive of subacute intestinal obstruction. He had progressive reduction in
white cell counts, platelets and derrangements in liver functions. The illness
mimicked acute severe leptospirosis or dengue. On day 9 of illness he started to
loose his hair and was totally alopecic by day 14. At this stage of illness,
possibility of GSb poisoning was suspected. He admitted the act of self harm
after repeated questioning. CONCLUSION: His presentation mimicked an acute severe
tropical febrile illness such as leptospirosis or dengue until he started to
loose his hair. Therefore we feel that Clinicians practicing in tropical setting
where Gloriosa superba is endemic should be aware of its clinical presentations
and should always consider the possibility of ingestion of Gloriosa superba when
the patient has pancytopenia and develops shedding of hairs which results in
total alopecia in a case of unexplained gastroenterocolitis, rather
investigating.
PMID- 26415510
TI - BARD1 mediates TGF-beta signaling in pulmonary fibrosis.
AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rapid progressive fibro
proliferative disorder with poor prognosis similar to lung cancer. The
pathogenesis of IPF is uncertain, but loss of epithelial cells and fibroblast
proliferation are thought to be central processes. Previous reports have shown
that BARD1 expression is upregulated in response to hypoxia and associated with
TGF-beta signaling, both recognized factors driving lung fibrosis. Differentially
spliced BARD1 isoforms, in particular BARD1beta, are oncogenic drivers of
proliferation in cancers of various origins. We therefore hypothesized that BARD1
and/or its isoforms might play a role in lung fibrosis. METHODS: We investigated
BARD1 expression as a function of TGF-beta in cultured cells, in mice with
experimentally induced lung fibrosis, and in lung biopsies from pulmonary
fibrosis patients. RESULTS: FL BARD1 and BARD1beta were upregulated in response
to TGF-beta in epithelial cells and fibroblasts in vitro and in vivo. Protein and
mRNA expression studies showed very low expression in healthy lung tissues, but
upregulated expression of full length (FL) BARD1 and BARD1beta in fibrotic
tissues. CONCLUSION: Our data suggest that FL BARD1 and BARD1beta might be
mediators of pleiotropic effects of TGF-beta. In particular BARD1beta might be a
driver of proliferation and of pulmonary fibrosis pathogenesis and progression
and represent a target for treatment.
PMID- 26415511
TI - Underweight body mass index is a risk factor of mortality in outpatients with
nocturia in Japan.
AB - BACKGROUND: Although nocturia has been reported to increase mortality in elderly
individuals, the particular risk factors that are associated with this event are
unclear. Therefore, we evaluated risk factors for death in outpatients with
nocturia. METHODS: Between October 2002 and December 2009, 250 consecutive
patients with nocturia were enrolled in two general hospitals in Japan. Among
them, 193 patients were able to be followed for at least 1 year and up to 9 years
(median 4.8 years) if the patients did not die. Mortality rates and risk factors
were evaluated in the nocturic outpatients. RESULTS: Two- and 5-year survival of
the nocturic outpatients was 94.6% [95% confidence interval (CI) = 92.2-97.1] and
82.6% (95% CI = 75.4-87.8), respectively. Higher Charlson Comorbidity Score,
lower body mass index (BMI) and lower Physical Component Summary of Short Form-36
item scores were significantly correlated with mortality (p < 0.0001, p < 0.005
and p < 0.05, respectively) in multivariate analysis. The International Prostate
Symptom Score, Pittsburgh Sleep Quality Index, Mental or Role/Social Component
Summary of Short Form-36 item scores and Nocturnal Polyuria index were not
significantly correlated with mortality. The mortality rate was significantly
higher in subjects with an underweight BMI (<18.50) compared with a normal range
(18.50-24.99) or overweight (>=25.00) BMI [p < 0.00005, hazard ratio (HR) = 5.84,
95% CI = 2.03-16.8; p < 0.0005, HR = 5.92, 95% CI = 1.94-18.0]. CONCLUSIONS:
Additional attention is required for nocturic outpatients with not only a high
Charlson Comorbidity Score but also an underweight BMI because of their high
mortality. Large prospective studies are warranted to validate this finding and
extend more.
PMID- 26415512
TI - Concurrent and predictive validity of physical activity measurement items
commonly used in clinical settings--data from SCAPIS pilot study.
AB - BACKGROUND: As the understanding of how different aspects of the physical
activity (PA) pattern relate to health and disease, proper assessment is
increasingly important. In clinical care, self-reports are the most commonly used
assessment technique. However, systematic comparisons between questions regarding
concurrent or criterion validity are rare, as are measures of predictive
validity. The aim of the study was to examine the concurrent (using accelerometry
as reference) and predictive validity (for metabolic syndrome) of five PA
questions. METHODS: A sample of 948 middle-aged Swedish men and women reported
their PA patterns via five different questions and wore an accelerometer
(Actigraph GT3X) for a minimum of 4 days. Concurrent validity was assessed as
correlations and ROC-analyses. Predictive validity was assessed using logistic
regression, controlling for potential confounders. RESULTS: Concurrent validity
was low-to-moderate (r <0.35 and ROC AUC <0.7) with large misclassifications
regarding time spent sitting/sedentary and in moderate-to vigorous PA. The
predictive validity of the questions was good, and one question (PHAS) showed an
80 % decreased odds-ratio of having metabolic syndrome, after taking potential
confounders into consideration. DISCUSSION: In this mixed sample of adults, both
concurrent and predictive validity vaired between items and between measures of
the physical activity pattern. The PHAS and WALK items are proposed for
assessment of adherence to PA recommendations. CONCLUSION: Assessing PA patterns
using self-report measures results in methodological problems when trying to
predict individual risk for the metabolic syndrome, as the concurrent validity
generally was low. However, several of the investigated questions may be useful
for assessing risk at a group level, showing better predictive validity.
PMID- 26415514
TI - Probing the interaction of Rh, Co and bimetallic Rh-Co nanoparticles with the
CeO2 support: catalytic materials for alternative energy generation.
AB - The interaction of CeO2-supported Rh, Co and bimetallic Rh-Co nanoparticles,
which are active catalysts in hydrogen production via steam reforming of ethanol,
a process related to renewable energy generation, was studied by X-ray
diffraction (XRD), high resolution electron microscopy (HRTEM), X-ray
photoelectron spectroscopy (XPS) and low energy ion scattering (LEIS).
Furthermore, diffuse reflectance infrared spectroscopy (DRIFTS) of adsorbed CO as
a probe molecule was used to characterize the morphology of metal particles. At
small loadings (0.1%), Rh is in a much dispersed state on ceria, while at higher
contents (1-5%), Rh forms 2-8 nm particles. Between 473-673 K pronounced oxygen
transfer from ceria to Rh is observed and at 773 K significant agglomeration of
Rh occurs. On reduced ceria, XPS indicates a possible electron transfer from Rh
to ceria. The formation of smaller ceria crystallites upon loading with Co was
concluded from XRD and HRTEM; for 10% Co, the CeO2 particle size decreased from
27.6 to 10.7 nm. A strong dissolution of Co into ceria and a certain extent of
encapsulation by ceria were deduced by XRD, XPS and LEIS. In the bimetallic
system, the presence of Rh enhances the reduction of cobalt and ceria. During
thermal treatments, reoxidation of Co occurs, and Rh agglomeration as well as
oxygen migration from ceria to Rh are hindered in the presence of cobalt.
PMID- 26415513
TI - Mini-Tn7 vectors for stable expression of diguanylate cyclase PleD* in Gram
negative bacteria.
AB - BACKGROUND: The cyclic diguanylate (c-di-GMP) is currently considered an
ubiquitous second messenger in bacteria that influences a wide range of cellular
processes. One of the methodological approaches to unravel c-di-GMP regulatory
networks involves raising the c-di-GMP intracellular levels, e.g. by expressing a
diguanylate cyclase (DGC), to provoke phenotypic changes. RESULTS: We have
constructed mini-Tn7 delivery vectors for the integration and stable expression
of the pleD* gene encoding a highly active DGC, which can be used to artificially
increase the intracellular levels of c-di-GMP in Gram negative bacteria. The
functionality of these new vectors has been validated in several plant
interacting alpha- and gamma-proteobacteria. Similarly to vector plasmid-borne
pleD*, the genome-borne mini-Tn7pleD* constructs provide significant increases in
intracellular c-di-GMP, provoking expected phenotypic changes such as enhanced
polysaccharide production, biofilm formation and reduced motility. However, the
mini-Tn7pleD* constructs resulted far more stable in the absence of antibiotics
than the plasmid-based pleD* constructs. Furthermore, we have also implemented an
inducible system to modulate pleD* expression and intracellular c-di-GMP rises
"on demand". CONCLUSIONS: mini-Tn7pleD* constructs are very stable and are
maintained during bacterial free-living growth as well as during interaction with
eukaryotic hosts, in the absence of selective pressure. This high stability
ensures experimental homogeneity in time and space with regard to enhancing c-di
GMP intracellular levels in bacteria of interest.
PMID- 26415515
TI - Photobiological properties of 3-psoralenacetic acids.
AB - Some 4,8-dimethyl-3-psoralenacetic acids were synthesized and studied. All the
designed psoralenacetic acids bear alkyl or cycloalkyl substituents at the furan
ring. These psoralenacetic acids were shown to be a novel class of psoralen
derivatives characterized by an interesting photobiological profile. The
carboxylic group at the 3 position, useful to confer hydrophilic properties,
appears to be detrimental to the classical intercalation into DNA, likely because
of repulsive interactions with the negative surface of the macromolecule.
Nevertheless, the new derivatives possess a notable photoantiproliferative
activity, due to a peculiar mechanism of action consisting of a decarboxylation
step before exerting their photobiological activity. The most active compound 2
is able to induce a noteworthy photocytotoxic effect, with GI50 values being
submicromolar on human tumor cell lines and no effect in the dark. The
involvement of DNA photoaddition after UVA light-mediated decarboxylation and ROS
formation is responsible for its biological activity, as demonstrated comparing
the activity profile of the decarboxylated analogue. However, other biological
targets seem to be involved in the photooxidative damage, such as proteins.
Compound 2 could thus be considered as a prodrug, inactive without UVA light but
activated upon specific irradiation, thus preventing unselective side effects and
opening new perspectives on agents useful in photochemotherapy.
PMID- 26415516
TI - Full-color structured illumination optical sectioning microscopy.
AB - In merits of super-resolved resolution and fast speed of three-dimensional (3D)
optical sectioning capability, structured illumination microscopy (SIM) has found
variety of applications in biomedical imaging. So far, most SIM systems use
monochrome CCD or CMOS cameras to acquire images and discard the natural color
information of the specimens. Although multicolor integration scheme are
employed, multiple excitation sources and detectors are required and the spectral
information is limited to a few of wavelengths. Here, we report a new method for
full-color SIM with a color digital camera. A data processing algorithm based on
HSV (Hue, Saturation, and Value) color space is proposed, in which the recorded
color raw images are processed in the Hue, Saturation, Value color channels, and
then reconstructed to a 3D image with full color. We demonstrated some 3D optical
sectioning results on samples such as mixed pollen grains, insects, micro-chips
and the surface of coins. The presented technique is applicable to some
circumstance where color information plays crucial roles, such as in materials
science and surface morphology.
PMID- 26415517
TI - Underperception of Naps in Older Adults Referred for a Sleep Assessment: An
Insomnia Trait and a Cognitive Problem?
AB - OBJECTIVES: To examine the frequency and determinants of underperception of naps
in older adults referred for a sleep assessment. DESIGN: Prospective study.
SETTING: Outpatient geriatric sleep clinic. PARTICIPANTS: Individuals aged 60 and
older referred for insomnia complaints or suspected sleep apnea (N = 135).
MEASUREMENTS: Tests included clinical interview, sleepiness scale, anxiety and
depression scale, Insomnia Severity Index (ISI), Mini-Mental State Examination
(MMSE), and overnight polysomnography, followed by multiple sleep latency tests.
At the end of each of four nap opportunities, participants answered whether they
had slept during the test. Nap underperception was defined as two or more
unperceived naps. RESULTS: Of the 105 participants who napped at least twice, 42
(40%) did not perceive at least two naps. These participants had lower MMSE
scores (P = .01) and were more likely to be taking benzodiazepines (P = .008)
than the 63 participants who did not underperceive their naps but had similar
demographic characteristics, sleep diagnoses, depression and anxiety scores, and
polysomnography measures. Both groups had similarly short mean daytime sleep
latencies (9.7 +/- 4.5 minutes and 9.8 +/- 3.7 minutes), but participants who
underperceived their naps scored lower on the Epworth Sleepiness Scale (5.6 +/-
4.0, vs 9.6 +/- 4.8, P < .001). An ISI of 11 or greater, a MMSE score of 26 or
less, and a sleepiness score of 8 or less were each independently associated with
underperception of naps. The combination of these three factors yielded a
positive predictive value of 93% and a negative predictive value of 71% for nap
underperception. CONCLUSION: Older adults referred for sleep consultation with
cognitive impairment and greater insomnia symptoms frequently underperceive naps,
leading them to underestimate their level of sleepiness. In such cases, objective
measures of daytime sleepiness would be better than the Epworth Sleepiness Scale.
PMID- 26415519
TI - Vitamin D Supplementation in the Treatment of Chronic Heart Failure: A Meta
analysis of Randomized Controlled Trials.
AB - BACKGROUND: In recent years, there has been growing evidence that vitamin D
deficiency is associated with the development and progression of chronic heart
failure (CHF). HYPOTHESIS: Additional supplementation of vitamin D may have
protective effects in patients with CHF. METHODS: We searched PubMed, Embase, and
Cochrane databases through June 2015 and included 7 randomized controlled trials
that investigated the effects of vitamin D on cardiovascular outcomes in patients
with CHF. Then, we performed a meta-analysis of clinical trials to confirm
whether vitamin D supplementation is beneficial in CHF patients. The weighted
mean difference (WMD) and 95% confidence interval (CI) were calculated using
fixed- or random-effects models. RESULTS: Our pooled results indicated that
additional supplementation of vitamin D was not superior to conventional
treatment in terms of left ventricular ejection fraction, N-terminal pro-B-type
natriuretic peptide, and 6-minute walk distance. Moreover, vitamin D
supplementation was associated with significant decreases in the levels of tumor
necrosis factor-alpha (WMD: -2.42 pg/mL, 95% CI: -4.26 to -0.57, P < 0.05), C
reactive protein (WMD: -0.72 mg/L, 95% CI: -1.42 to -0.02, P < 0.05), and
parathyroid hormone (WMD: -13.44 pg/mL, 95% CI: -21.22 to -5.67, P < 0.05).
CONCLUSIONS: Vitamin D supplementation may decrease serum levels of parathyroid
hormone and inflammatory mediators in CHF patients, whereas it has no beneficial
effects on improvement of left ventricular function and exercise tolerance.
PMID- 26415520
TI - Randomized controlled trial of a self-efficacy enhancement program for the
cardiac rehabilitation of Thai patients with myocardial infarction.
AB - This study examined the effects of a self-efficacy enhancement program for the
cardiac rehabilitation of Thai patients who had a myocardial infarction. Sixty
six hospitalized patients of various ages and both genders were randomly assigned
to either an experimental or a control group. Participants in the experimental
group took part in three individualized in-hospital education sessions and three
weekly sessions of telephone counseling. The control group primarily engaged in a
supervised exercise and activities of a daily living performance regimen, and
received education in this regard. Self-efficacy and functional status were
measured via questionnaire. Four weeks after discharge, the experimental group
was found to have significantly higher total self-efficacy and functional status
scores than the control group. In addition, the experimental group exhibited
significantly higher subscale scores on social activity, household tasks,
occupation, and exercise self-efficacy than the control group. These results
indicate that the program is effective in improving the self-efficacy and
functional status of Thai patients who have had a myocardial infarction.
PMID- 26415521
TI - Adult pre B-cell acute lymphoblastic leukemia with unusually large proportion of
bone marrow CD45 bright/high SSc blasts.
AB - BACKGROUND: We present a pre B-ALL patient with the rare clinical manifestation
of extramedullary disease, and a normal hemogram. This patient's blasts expressed
bright CD45 and high side scatter (SSc) placing the cells in the monocyte gate.
METHODS: Samples from peripheral blood and bone marrow (BM) aspirate from a 50
year-old female patient were immunophenotyped by multiparametric flow cytometry.
RESULTS: Flow cytometry studies of the BM aspirate showed a large monocyte gate
with 90-95% of the cells expressing an abnormal B cell phenotype. Peripheral
white blood cells count was normal and cytogenetic analysis of the BM revealed a
normal karyotype. CONCLUSION: It was not possible, based on CD45/SSc to identify
a lymphoblast population in this pre B-ALL patient. Although bright expression of
CD45 B-ALL blasts has been associated with poor prognosis to the best of our
knowledge, the combination of bright CD45 blasts with high SSc has not been
reported. As CD45 expression vs. SSc is routinely measured in the diagnostics of
acute leukemias, a possible association between CD45 bright positivity and
extramedullary disease or prognosis warrants further exploration. (c) 2015
International Clinical Cytometry Society.
PMID- 26415522
TI - Multicomponent One-pot Reactions Towards the Synthesis of Stereoisomers of
Dipicolylamine Complexes.
AB - Reported are multi-component one-pot syntheses of chiral complexes [M(L(R)
OR')Cl2 ] or [M(L(R) SR')Cl2 ] from the mixture of an N-substituted
ethylenediamine, pyridine-2-carboxaldehyde, a primary alcohol or thiol and MCl2
utilizing in-situ formed cyclized Schiff bases where a C-O bond, two
stereocenters, and three C-N bonds are formed (M=Zn, Cu, Ni, Cd; R=Et, Ph; R'=Me,
Et, nPr, nBu). Tridentate ligands L(R) OR' and L(R) SR' comprise two chiral
centers and a hemiaminal ether or hemiaminal thioether moiety on the
dipicolylamine skeleton. Syn-[Zn(L(Ph) OMe)Cl2 ] precipitates out readily from
the reaction mixture as a major product whereas anti-[Zn(L(Ph) OMe)Cl2 ] stays in
solution as minor product. Both syn-[Zn(L(Ph) OMe)Cl2 ] and anti-[Zn(L(Ph)
OMe)Cl2 ] were characterized using NMR spectroscopy and mass spectrometry. Solid
state structures revealed that syn-[Zn(L(Ph) OMe)Cl2 ] adopted a square pyramidal
geometry while anti-[Zn(L(Ph) OMe)Cl2 ] possesses a trigonal bipyramidal geometry
around the Zn centers. The scope of this method was shown to be wide by varying
the components of the dynamic coordination assembly, and the structures of the
complexes isolated were confirmed by NMR spectroscopy, mass spectrometry, and X
ray crystallography. Syn complexes were isolated as major products with Zn(II)
and Cu(II) , and anti complexes were found to be major products with Ni(II) and
Cd(II) . Hemiaminals and hemiaminal ethers are known to be unstable and are
seldom observed as part of cyclic organic compounds or as coordinated ligands
assembled around metals. It is now shown, with the support of experimental
results, that linear hemiaminal ethers or thioethers can be assembled without the
assistance of Lewis acidic metals in the multi-component assembly, and a possible
pathway of the formation of hemiaminal ethers has been proposed.
PMID- 26415518
TI - Matrix metalloproteinase-10: a novel biomarker for idiopathic pulmonary fibrosis.
AB - BACKGROUND: Matrix metalloproteinases (MMPs) are believed to be involved in the
pathogenesis of idiopathic pulmonary fibrosis (IPF), and MMP-7 has been described
as a useful biomarker for IPF. However, little is known regarding the
significance of MMP-10 as a biomarker for IPF. METHODS: This observational cohort
study included 57 patients with IPF. Serum MMPs were comprehensively measured in
all patients, and the relationships between these markers and both disease
severity and prognosis were evaluated. Bronchoalveolar lavage fluid (BALF) MMP-7
and -10 levels were measured in 19 patients to investigate the correlation
between these markers and their corresponding serum values. Immunohistochemical
staining for MMP-10 was also performed in IPF lung tissue. RESULTS: Serum MMP-7
and -10 levels correlated significantly with both the percentage of predicted
forced vital capacity (rho = -0.31, p = 0.02 and rho = -0.34, p < 0.01,
respectively) and the percentage of predicted diffusing capacity of the lung for
carbon monoxide (rho = -0.32, p = 0.02 and rho = -0.43, p < 0.01, respectively).
BALF MMP-7 and -10 levels correlated with their corresponding serum
concentrations. Only serum MMP-10 predicted clinical deterioration within 6
months and overall survival. In IPF lungs, the expression of MMP-10 was enhanced
and localized to the alveolar epithelial cells, macrophages, and peripheral
bronchiolar epithelial cells. CONCLUSIONS: MMP-10 may be a novel biomarker
reflecting both disease severity and prognosis in patients with IPF.
PMID- 26415523
TI - Functional and Clinical Consequences of Novel alpha-Galactosidase A Mutations in
Fabry Disease.
AB - Fabry disease (FD) is a rare metabolic disorder of glycosphingolipid storage
caused by mutations in the GLA gene encoding lysosomal hydrolase alpha
galactosidase A (alpha-gal A). Recently, the diagnostic procedure for FD has
advanced in several ways, through the development of a specific biomarker (lyso
Gb3) and the implementation of newborn screenings, which acted as a catalyst to
augment general awareness of the disease. Heterologous over-expression of alpha
gal A variants and subsequent in vitro measurement of enzyme activity provided
molecular data to elucidate the relationship between mutation, enzyme damage,
lyso-Gb3 biomarker levels, and clinical phenotype. This knowledge is the
foundation for improved counseling with regard to prognosis and therapeutic
decisions. Herein, we resume the approach of in vitro characterization, with a
further 73 mainly novel GLA gene mutations. Patient lyso-Gb3 data were available
for most of the mutations. All mutations were tested for responsiveness to
pharmacological chaperone treatment and phenotypic data for 61 hemizygous male
and 116 heterozygous female patients carrying a mutation associated with >= 20%
residual activity, formerly classified as "mild" variant, were collected in order
to evaluate the pathogenicity. We conclude that a mild GLA variant is typically
characterized by high residual enzyme activity and normal biomarker levels. We
found evidence that these variants can still be classified as a distinctive, but
milder, sub-type of FD.
PMID- 26415524
TI - Colloidal dual-band gap cell for photocatalytic hydrogen generation.
AB - We report that the internal quantum efficiency for hydrogen generation in
spherical, Pt-decorated CdS nanocrystals can be tuned by quantum confinement,
resulting in higher efficiencies for smaller than for larger nanocrystals (17.3%
for 2.8 nm and 11.4% for 4.6 nm diameter nanocrystals). We attribute this to a
larger driving force for electron and hole transfer in the smaller nanocrystals.
The larger internal quantum efficiency in smaller nanocrystals enables a novel
colloidal dual-band gap cell utilising differently sized nanocrystals and showing
larger external quantum efficiencies than cells with only one size of
nanocrystals (9.4% for 2.8 nm particles only and 14.7% for 2.8 nm and 4.6 nm
nanocrystals). This represents a proof-of-principle for future colloidal tandem
cell.
PMID- 26415525
TI - Clinical and neurobiological advances in promoting regeneration of the ventral
root avulsion lesion.
AB - Root avulsions due to traction to the brachial plexus causes complete and
permanent loss of function. Until fairly recent, such lesions were considered
impossible to repair. Here we review clinical repair strategies and current
progress in experimental ventral root avulsion lesions. The current gold standard
in patients with a root avulsion is nerve transfer, whereas reimplantation of the
avulsed root into the spinal cord has been performed in a limited number of
cases. These neurosurgical repair strategies have significant benefit for the
patient but functional recovery remains incomplete. Developing new ways to
improve the functional outcome of neurosurgical repair is therefore essential. In
the laboratory, the molecular and cellular changes following ventral root
avulsion and the efficacy of intervention strategies have been studied at the
level of spinal motoneurons, the ventral spinal root and peripheral nerve, and
the skeletal muscle. We present an overview of cell-based pharmacological and
neurotrophic factor treatment approaches that have been applied in combination
with surgical reimplantation. These interventions all demonstrate neuroprotective
effects on avulsed motoneurons, often accompanied with various degrees of axonal
regeneration. However, effects on survival are usually transient and robust axon
regeneration over long distances has as yet not been achieved. Key future areas
of research include finding ways to further extend the post-lesion survival
period of motoneurons, the identification of neuron-intrinsic factors which can
promote persistent and long-distance axon regeneration, and finally prolonging
the pro-regenerative state of Schwann cells in the distal nerve.
PMID- 26415527
TI - Maternal and paternal support for physical activity and healthy eating in
preschool children: a cross-sectional study.
AB - BACKGROUND: Parental support is a key influence on children's health behaviours;
however, no previous investigation has simultaneously explored the influence of
mothers' and fathers' social support on eating and physical activity in preschool
aged children. This study evaluated the singular and combined effects of maternal
and paternal support for physical activity (PA) and fruit and vegetable
consumption (FV) on preschoolers' PA and FV. METHODS: A random sample comprising
173 parent-child dyads completed validated scales assessing maternal and paternal
instrumental support and child PA and FV behaviour. Pearson correlations,
controlling for child age, parental age, and parental education, were used to
evaluate relationships between maternal and paternal support and child PA and FV.
K-means cluster analysis was used to identify families with distinct patterns of
maternal and paternal support for PA and FV, and one-way ANOVA examined the
impact of cluster membership on child PA and FV. RESULTS: Maternal and paternal
support for PA were positively associated with child PA (r = 0.37 and r = 0.36,
respectively; P < 0.001). Maternal but not paternal support for FV was positively
associated with child FV (r = 0.35; P < 0.001). Five clusters characterised
groups of families with distinct configurations of maternal and paternal support
for PA and FV: 1) above average maternal and paternal support for PA and FV, 2)
below average maternal and paternal support for PA and FV, 3) above average
maternal and paternal support for PA but below average maternal and paternal
support for FV, 4) above average maternal and paternal support for FV but below
average maternal and paternal support for PA, and 5) above average maternal
support but below average paternal support for PA and FV. Children from families
with above average maternal and paternal support for both health behaviours had
higher PA and FV levels than children from families with above average support
for just one health behaviour, or below average support for both behaviours.
CONCLUSIONS: The level and consistency of instrumental support from mothers and
fathers for PA and FV may be an important target for obesity prevention in
preschool-aged children.
PMID- 26415526
TI - Epidemiology of invasive candidiasis in a surgical intensive care unit: an
observational study.
AB - BACKGROUND: Invasive candidiasis (IC) is a frequent and life-threatening
infection in critically ill patients. The aim of this study was to evaluate the
epidemiology of IC and the antifungal susceptibility of etiological agents in
patients admitted to our surgical intensive care unit (SICU) in Spain. METHODS:
We designed a prospective, observational, single center, population-based study
in a SICU. We included all consecutive adult patients (>=18 years old) who had
documented IC, either on admission or during their stay, between January 2012 and
December 2013. RESULTS: There were a total of 22 episodes of IC in the 1149
patients admitted during the 24-month study. The overall IC incidence was 19.1
cases per 1000 admissions. Thirteen cases of IC (59.1%) were intra-abdominal
candidiasis (IAC) and 9 (40.9%) were candidemias. All cases of IAC were patients
with secondary peritonitis and severe sepsis or septic shock. The overall crude
mortality rate was 13.6%; while, it was 33% in patients with candidemia. All
patients with IAC survived, including one patient with concomitant candidemia.
The most common species causing IC was Candida albicans (13; 59.1%) followed by
Candida parapsilosis (5; 22.7%), and Candida glabrata (2; 9.1%). There was also
one case each (4.5%) of Candida krusei and Candida tropicalis. Thus, the ratio of
non-C. albicans (9) to C. albicans (13) was 1:1.4. There was resistance to
fluconazole and itraconazole in 13.6% of cases. Resistance to other antifungals
was uncommon. CONCLUSIONS: Candida parapsilosis was the second most common
species after C. albicans, indicating the high prevalence of non-C. albicans
species in the SICU. Resistance to azoles, particularly fluconazole, should be
considered when starting an empirical treatment. Although IAC is a very frequent
form of IC in critically ill surgical patients, prompt antifungal therapy and
adequate source control appears to lead to a good outcome. However, our results
are closely related to our ICU and any generalization must be taken with caution.
Therefore, further investigations are needed.
PMID- 26415528
TI - A meta-analysis of in vitro antibiotic synergy against Acinetobacter baumannii.
AB - The aim of the work was to describe the different in vitro models for testing
synergism of antibiotics and gather the results of antibiotic synergy against
multidrug-resistant Acinetobacter baumannii (MDR-Ab). The different original
articles were obtained from different web sites. In order to compare the results
obtained by the different methods for synergy testing, the Pearson chi-square and
the Fischer tests were used. Moreover, non-parametric chi-square test was used in
order to compare the frequency distribution in each analysed manuscript. In the
current meta-analysis 24 manuscripts, which encompassed 2016 tests of in vitro
synergism of different antimicrobials against MDR-Ab, were revised. Checkerboard
synergy testing was used in 11 studies, which encompasses 1086 tests (53.9%);
time-kill assays were applied in 12 studies, which encompass 359 tests (17.8%);
gradient diffusion methods were used in seven studies, encompassing 293 tests
(14.5%). And, finally, time-kill plus checkerboard were applied in two studies,
encompassing 278 tests (13.8%). By comparing these data, checkerboard and time
kill methods were significantly more used than gradient diffusion methods
(p<0.005). Regarding synergy rates obtained on the basis of the applied method,
checkerboard provided 227 tests (20.9%) with a synergistic effect; time-kill
assays yielded 222 tests (61.8%) with a synergistic effect; gradient diffusion
methods only provided 29 tests (9.9%) with a synergistic effect; and, finally,
time-kill plus checkerboard yielded just 15 tests (5.4%) with a synergistic
effect. When comparing these percentages, synergy rates reported by time-kill
methods were significantly higher than that obtained by checkerboard and gradient
diffusion methods (p<0.005). On the basis of the revised data, the combinations
of a bactericidal antibiotic plus Tigecycline, Vancomycin or Teicoplanin are not
recommended. The best combinations of antibiotics are those which include
bactericidal antibiotics such as Carbapenems, Fosfomycin, Amikacin, Polymyxins,
Rifampicin and Ampicillin/Sulbactam.
PMID- 26415529
TI - Detection of Escherichia coli sequence type 131 clonal group among extended
spectrum beta-lactamase-producing E. coli using VITEK MS Plus matrix-assisted
laser desorption ionization-time of flight mass spectrometry.
AB - We investigated the performance of the VITEK MS Plus system for the detection of
Escherichia coli sequence type 131 (ST131) among extended-spectrum beta-lactamase
producing E. coli isolates. The SARAMIS software could discriminate the 67 ST131
isolates from 82 non-ST131 isolates with a sensitivity of 86.6% and a specificity
of 95.1%.
PMID- 26415530
TI - Immunoproteomic technology offers an extraordinary diagnostic approach for
Toxoplasma gondii infection.
AB - Immunoproteomic technology offers an exceptional tool to fill the blanks that
still exist in diagnosis of Toxoplasma gondii infection despite its annotated
sequence. The pitfalls of serological assays and current immunoproteomic
approaches are accentuated, and new approaches are presented to improve the
signal and to eliminate the noise produced by blocking-specific background. This
review also highlights examples where immunoproteomic studies have contributed to
broaden our understanding of toxoplasmosis diagnosis. Further promising
solutions, which immunoproteomic technology can grant for toxoplasmosis diagnosis
are part of an intense discussion.
PMID- 26415531
TI - The effects of arginase inhibitor on lung oxidative stress and inflammation
caused by pneumoperitoneum in rats.
AB - BACKGROUND: Pneumoperitoneum-induced oxidative stress and organ injury are known
to be associated with nitric oxide (NO) inactivation. Because arginase competes
with NO synthase (NOS) for a common substrate, L-arginine, arginase inhibition
may increase NO bioavailability. Therefore, we evaluated the ability of the
arginase inhibitor, 2 (S)-amino-6-boronohexanoic acid (ABH), to attenuate
pneumoperitoneum-induced decrease of NO bioavailability and lung injury. METHODS:
Thirty rats were randomly divided into the following groups: 1) the PP-ABH group
received a subcutaneous injection of ABH (5 mg/kg) 1 h before induction of
pneumoperitoneum (insufflation to intraperitoneal pressure of 15 mmHg for 60
min); 2) the PP group received saline by subcutaneous injection 1 h before
induction of pneumoperitoneum; and 3) the control group received saline by
subcutaneous injection before a sham procedure with no gas insufflation. After
desufflation, blood was collected to determine levels of plasma nitrite, NOS,
inflammatory cytokines, and malondialdehyde, a marker of oxidative stress. Lung
tissue was obtained for histological evaluation. RESULTS: We found that plasma
nitrite levels were lower in the PP group and higher in the PP-ABH group,
compared with controls (P <0.01 and P <0.05, respectively). In the PP group,
endothelial NOS activity was decreased and inducible NOS activity was increased
compared with the PP-ABH and control groups. Malondialdehyde levels increased 3
fold in the PP group and 2-fold in the PP-ABH group compared with controls. Tumor
necrosis factor-alpha, interleukin-6, and interleukin-1beta levels were elevated
in the PP group compared to the control group, but the increase in cytokine
production was attenuated or blocked in the PP-ABH group. Lung injury scores were
4.8-fold higher in the PP group and 2-fold higher in the PP-ABH group compared
with controls (P <0.001 and P <0.01, respectively). DISCUSSION: Pneumoperitoneum
decreases NO bioavailability and increases the inflammation cytokines, resulting
in organ injuries. Inhibition of arginase activity could maintain NO
bioavailability by attenuating pneumoperitoneum-induced changes in NOS activity.
In addition, arginase inhibition attenuated the oxidative stress and inflammation
and decreased the severity of lung injury caused by pneumoperitoneum.
CONCLUSIONS: By increasing NO bioavailability and suppressing oxidative stress
and inflammation, pretreatment with an arginase inhibitor may protect against
lung injury caused by pneumoperitoneum.
PMID- 26415533
TI - Avoiding pediatric readmissions: Quite a challenge!
PMID- 26415532
TI - Antioxidant and cytotoxic activities of three species of tropical seaweeds.
AB - BACKGROUND: Three species of seaweeds (Padina tetrastromatica, Caulerpa racemosa
and Turbinaria ornata) are widely consumed by Asians as nutraceutical food due to
their antioxidant properties. Studies have shown that these seaweeds exhibit
bioactivities which include antimicrobial, antiviral, anti-hypertensive and
anticoagulant activities. However, investigations into the mechanisms of action
pertaining to the cytotoxic activity of the seaweeds are limited. The aim of this
study was to determine the antioxidant and cytotoxic activities of whole extracts
of P. tetrastromatica, C. racemosa and T. ornata, including the cellular events
leading to the apoptotic cell death of the extract treated-MCF-7 cells. Bioassay
guided fractionation was carried out and the compounds identified. METHODS:
Powdered samples were sequentially extracted for 24 h. Their antioxidant
activities were assessed by the DPPH radical, superoxide, nitric oxide and
hydroxyl radical scavenging assays. The cytotoxic activity of the extract-treated
MCF-7cells was assessed using the MTT assay. The most potent fraction was
subjected to bioassay guided fractionation with column chromatography. All the
fractions were tested for cytotoxic activity, caspase activity and effect on DNA
fragmentation. RESULTS: All three seaweeds showed potent radical scavenging
activities in the various assays. The activity of the cellular antioxidant
enzymes, superoxide dismutase, catalase and glutathione reductase, in MCF-7
cells, decreased in a time-dependent manner. The partially purified fractions
exhibited higher cytotoxic activity, as assessed by the MTT assay, than the whole
extracts in the breast adenocarcinoma cell line, MCF-7. LC-MS analysis revealed
the presence of bioactive alkaloids such as camptothecin, lycodine and
pesudopelletierine. CONCLUSION: Based on the results obtained, all three seaweeds
are rich sources of enzymatic and non-enzymatic antioxidants which could
contribute to their reported medicinal benefits.
PMID- 26415534
TI - Takotsubo cardiomyopathy: Near drowning and hanging sound familiar.
PMID- 26415535
TI - Relationship between a perioperative intravenous fluid administration strategy
and acute kidney injury following off-pump coronary artery bypass surgery: an
observational study.
AB - INTRODUCTION: Saline-based and hydroxyethyl starch solutions are associated with
increased risk of renal dysfunction. In the present study, we tested the
hypothesis that balanced solutions and a limited volume of hydroxyethyl starch
solution (renal protective fluid management [RPF] strategy) would decrease the
incidence of postoperative acute kidney injury (AKI) and improve clinical
outcomes in patients undergoing off-pump coronary artery bypass graft surgery
(OPCAB). METHODS: We investigated 783 patients who underwent elective OPCAB. All
patients who underwent OPCAB between 1 January 2010 and 4 July 2012 formed the
control group and were given intravenous fluids with saline-based solutions and
unlimited volumes of colloid solutions. All patients who underwent OPCAB between
5 July 2012 and 31 December 2013 formed the RPF group and were given intravenous
fluids with RPF. The primary outcome was the incidence of postoperative AKI.
Secondary outcomes included the incidence of severe AKI, requirement for renal
replacement therapy, renal outcome at the time of discharge, and other clinical
outcomes. RESULTS: Postoperative AKI occurred in 33 patients (14.4 %) in the RPF
group compared with 210 patients (37.9 %) in the control group (P < 0.001). The
incidences of severe AKI and persistent AKI after OPCAB were significantly lower,
and the postoperative extubation time and duration of hospital stay were
significantly shorter, in patients in the RPF group than in those in the control
group. After adjustment by multivariate regression analyses and inverse
probability of treatment weighting adjustment, the RPF group was independently
associated with a lower incidence of postoperative AKI, severe AKI, and
persistent AKI and a shorter postoperative extubation time and duration of
hospital stay. CONCLUSIONS: The RPF strategy is associated with a significantly
decreased incidence of postoperative, severe, and persistent AKI in patients
undergoing OPCAB, although residual confounding may be present.
PMID- 26415536
TI - Homograft reconstruction of the right ventricular outflow tract in adults with
congenital heart disease: a systematic review.
AB - Reconstruction of the right ventricular outflow tract with a homograft is an
established surgical method in congenital heart disease. Studies from children
and adolescents suggest that homograft durability is shorter than the life
expectancy of the patient; therefore, durability in adults is addressed in this
systematic review. The PubMed database was searched in May 2012 and repeated in
May 2015 with the terms 'homograft AND pulmonary valve', generating 665 hits. We
included only studies involving more than 50 patients with a mean or median age
>18 years. Six studies with a cumulative total of 560 patients were included. The
long-term mortality rate was 2-8.8% at 8.1-10 years. Reintervention was common
during patients' life spans, with a 10-year event-free survival rate of 78-80%.
Early postoperative echocardiographic or magnetic resonance imaging defects
appear to predict rapid homograft degeneration. Further studies on various
malformations and risk markers for degeneration are needed to make qualified and
accurate decisions regarding lifetime management.
PMID- 26415537
TI - Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin
plasticity.
AB - Many behavioral experiences are known to promote hippocampal neurogenesis. In
contrast, the ability of behavioral experiences to influence the production of
oligodendrocytes and myelin sheath formation remains relatively unknown. However,
several recent studies indicate that voluntary exercise and environmental
enrichment can positively influence both oligodendrogenesis and myelination, and
that, in contrast, social isolation can negatively influence myelination. In this
review we summarize studies addressing the influence of behavioral experiences on
oligodendrocyte lineage cells and myelin, and highlight potential mechanisms
including experience-dependent neuronal activity, metabolites, and stress
effectors, as well as both local and systemic secreted factors. Although more
study is required to better understand the underlying mechanisms by which
behavioral experiences regulate oligodendrocyte lineage cells, this exciting and
newly emerging field has already revealed that oligodendrocytes and their
progenitors are highly responsive to behavioral experiences and suggest the
existence of a complex network of reciprocal interactions among oligodendrocyte
lineage development, behavioral experiences, and brain function. Achieving a
better understanding of these relationships may have profound implications for
human health, and in particular, for our understanding of changes in brain
function that occur in response to experiences. This article is part of the
Special Issue entitled 'Oligodendrocytes in Health and Disease'.
PMID- 26415539
TI - Enhanced photoelectrocatalytic performance of alpha-Fe2O3 thin films by surface
plasmon resonance of Au nanoparticles coupled with surface passivation by atom
layer deposition of Al2O3.
AB - The short lifetime of photogenerated charge carriers of hematite (alpha-Fe2O3)
thin films strongly hindered the PEC performances. Herein, alpha-Fe2O3 thin films
with surface nanowire were synthesized by electrodeposition and post annealing
method for photoelectrocatalytic (PEC) water splitting. The thickness of the
alpha-Fe2O3 films can be precisely controlled by adjusting the duration of the
electrodeposition. The Au nanoparticles (NPs) and Al2O3 shell by atom layer
deposition were further introduced to modify the photoelectrodes. Different
constructions were made with different deposition orders of Au and Al2O3 on Fe2O3
films. The Fe2O3-Au-Al2O3 construction shows the best PEC performance with 1.78
times enhancement by localized surface plasmon resonance (LSPR) of NPs in
conjunction with surface passivation of Al2O3 shells. Numerical simulation was
carried out to investigate the promotion mechanisms. The high PEC performance for
Fe2O3-Au-Al2O3 construction electrode could be attributed to the Al2O3
intensified LSPR, effective surface passivation by Al2O3 coating, and the
efficient charge transfer due to the Fe2O3-Au Schottky junctions.
PMID- 26415538
TI - Gabapentin potentiates sensitivity to the interoceptive effects of alcohol and
increases alcohol self-administration in rats.
AB - Gabapentin, a drug used in the treatment of epileptic seizures and neuropathic
pain, has shown efficacy in the treatment of alcohol dependence. Moreover, given
that gabapentin is used in the general population (e.g., non-dependent
individuals, social drinkers), we sought to utilize preclinical assessments to
examine the effects of gabapentin on sensitivity to moderate alcohol doses and
alcohol self-administration in rats with a history of moderate drinking. To this
end, we assessed whether gabapentin (0, 10, 30, 120 mg/kg, IG) pretreatment
alters sensitivity to experimenter- and self-administered alcohol, and whether
gabapentin alone has alcohol-like discriminative stimulus effects in rats trained
to discriminate alcohol dose (1 g/kg, IG) vs. water. Second, we assessed whether
gabapentin (0, 10, 30, 60 mg/kg, IG) would alter alcohol self-administration.
Gabapentin pretreatment potentiated the interoceptive effects of both
experimenter-administered and self-administered alcohol in discrimination-trained
rats. Additionally, the highest gabapentin doses tested (30 and 120 mg/kg) were
found to have partial alcohol-like discriminative stimulus effects when
administered alone (e.g., without alcohol). In the self-administration trained
rats, gabapentin pretreatment (60 mg/kg) resulted in an escalation in alcohol
self-administration. Given the importance of interoceptive drug cues in priming
and maintaining self-administration, these data define a specific behavioral
mechanism (i.e., potentiation of alcohol effects) by which gabapentin may
increase alcohol self-administration in non-dependent populations.
PMID- 26415540
TI - Polarization Properties in Apertureless-Type Scanning Near-Field Optical
Microscopy.
AB - Polarization properties of apertureless-type scanning near-field optical
microscopy (a-SNOM) were measured experimentally and were also analyzed using a
finite-difference time-domain (FDTD) simulation. Our study reveals that the
polarization properties in the a-SNOM are maintained and the a-SNOM works as a
wave plate expressed by a Jones matrix. The measured signals obtained by the lock
in detection technique could be decomposed into signals scattered from near-field
region and background signals reflected by tip and sample. Polarization images
measured by a-SNOM with an angle resolution of 1 degrees are shown. FDTD
analysis also reveals the polarization properties of light in the area between a
tip and a sample are p-polarization in most of cases.
PMID- 26415541
TI - Paraboloid Structured Silicon Surface for Enhanced Light Absorption: Experimental
and Simulative Investigations.
AB - In this paper, we present an optical model that simulates the light trapping and
scattering effects of a paraboloid texture surface first time. This model was
experimentally verified by measuring the reflectance values of the periodically
textured silicon (Si) surface with the shape of a paraboloid under different
conditions. A paraboloid texture surface was obtained by electrochemical etching
Si in the solution of hydrofluoric acid, dimethylsulfoxide (DMSO), and deionized
(DI) water. The paraboloid texture surface has the advantage of giving a lower
reflectance value than the hemispherical, random pyramidal, and regular pyramidal
texture surfaces. In the case of parabola, the light can be concentrated in the
direction of the Si surface compared to the hemispherical, random pyramidal, and
regular pyramidal textured surfaces. Furthermore, in a paraboloid textured
surface, there can be a maximum value of 4 or even more by anisotropic etching
duration compared to the hemispherical or pyramidal textured surfaces which have
a maximum h/D (depth and diameter of the texture) value of 0.5. The reflectance
values were found to be strongly dependent on the h/D ratio of the texture
surface. The measured reflectance values were well matched with the simulated
ones. The minimum reflectance value of ~4 % was obtained at a wavelength of 600
nm for an h/D ratio of 3.75. The simulation results showed that the reflectance
value for the h/D ratio can be reduced to ~0.5 % by reducing the separations
among the textures. This periodic paraboloidal structure can be applied to the
surface texturing technique by substituting with a conventional pyramid textured
surface or moth-eye antireflection coating.
PMID- 26415542
TI - Controlled Fabrication of Nanoporous Oxide Layers on Zircaloy by Anodization.
AB - We have presented a mechanism to explain why the resulting oxide morphology
becomes a porous or a tubular nanostructure when a zircaloy is electrochemically
anodized. A porous zirconium oxide nanostructure is always formed at an initial
anodization stage, but the degree of interpore dissolution determines whether the
final morphology is nanoporous or nanotubular. The interpore dissolution rate can
be tuned by changing the anodization parameters such as anodization time and
water content in an electrolyte. Consequently, porous or tubular oxide
nanostructures can be selectively fabricated on a zircaloy surface by controlling
the parameters. Based on this mechanism, zirconium oxide layers with completely
nanoporous, completely nanotubular, and intermediate morphologies between a
nanoporous and a nanotubular structure were controllably fabricated.
PMID- 26415543
TI - Identification of novel nitroreductases from Bacillus cereus and their
interaction with the CB1954 prodrug.
AB - Directed enzyme prodrug therapy is a form of cancer chemotherapy in which
bacterial prodrug-activating enzymes, or their encoding genes, are directed to
the tumour before administration of a prodrug. The prodrug can then be activated
into a toxic drug at the tumour site, reducing off-target effects. The bacterial
nitroreductases are a class of enzymes used in this therapeutic approach and
although very promising, the low turnover rate of prodrug by the most studied
nitroreductase enzyme, NfnB from Escherichia coli (NfnB_Ec), is a major limit to
this technology. There is a continual search for enzymes with greater efficiency,
and as part of the search for more efficient bacterial nitroreductase enzymes,
two novel enzymes from Bacillus cereus (strain ATCC 14579) have been identified
and shown to reduce the CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) prodrug
to its respective 2'-and 4'-hydroxylamine products. Both enzymes shared features
characteristic of the nitro-FMN-reductase superfamily including non-covalently
associated FMN, requirement for the NAD(P)H cofactor, homodimeric, could be
inhibited by Dicoumarol (3,3'-methylenebis(4-hydroxy-2H-chromen-2-one)), and
displayed ping pong bi bi kinetics. Based on the biochemical characteristics and
nucleotide alignment with other nitroreductase enzymes, one enzyme was named
YdgI_Bc and the other YfkO_Bc. Both B. cereus enzymes had greater turnover for
the CB1954 prodrug compared with NfnB_Ec, and in the presence of added NADPH
cofactor, YfkO_Bc had superior cell killing ability, and produced mainly the 4'
hydroxylamine product at low prodrug concentration. The YfkO_Bc was identified as
a promising candidate for future enzyme prodrug therapy.
PMID- 26415545
TI - Ultrasound-guided bilateral stellate ganglion blockade to treat digital ischemia
in a patient with sepsis: a case report.
AB - PURPOSE: This case report describes the use of ultrasound-guided stellate
ganglion blockade to treat sepsis-related digital ischemia in the intensive care
unit (ICU). CLINICAL FEATURES: A 71-yr-old female was admitted to the ICU with
septic shock and acute respiratory distress syndrome (ARDS) following an initial
right hemicolectomy complicated by an anastomotic leak and peritonitis. The
patient's condition was further complicated by an abdominal abscess 22 days
later. She had type-2 diabetes mellitus and hypertension but no history of
vascular disease. With continuing sepsis from the abscess and requiring
mechanical ventilation due to ARDS, she developed upper limb digital ischemia
refractory to treatment with a low dose of dobutamine and isosorbide dinitrate.
We subsequently performed ultrasound-guided bilateral stellate ganglion blockade
with the intent of restoring perfusion to her fingers before digital necrosis
developed. One hour after each stellate ganglion block, the symptoms of digital
ischemia completely resolved. The benefit persisted for two days, and then a
repeat block was performed with similar results. CONCLUSIONS: This case
illustrates the potential advantages of ultrasound-guided stellate ganglion
blockade for the treatment of sepsis-related digital ischemia refractory to
standard therapy.
PMID- 26415544
TI - Functional expression of the 11 human Organic Anion Transporting Polypeptides in
insect cells reveals that sodium fluorescein is a general OATP substrate.
AB - Organic Anion Transporting Polypeptides (OATPs), encoded by genes of the Solute
Carrier Organic Anion (SLCO) family, are transmembrane proteins involved in the
uptake of various compounds of endogenous or exogenous origin. In addition to
their physiological roles, OATPs influence the pharmacokinetics and drug-drug
interactions of several clinically relevant compounds. To examine the function
and molecular interactions of human OATPs, including several poorly characterized
family members, we expressed all 11 human OATPs at high levels in the baculovirus
Sf9 cell system. We measured the temperature- and inhibitor-sensitive cellular
accumulation of sodium fluorescein and fluorescein-methotrexate, two fluorescent
substrates of the OATPs, OATP1B1 and 1B3. OATP1B1 and 1B3 were functional in Sf9
cells, showing rapid uptake (t1/2(fluorescein-methotrexate) 2.64 and 4.16 min,
and t1/2(fluorescein) 6.71 and 5.58 min for OATP1B1 and 1B3, respectively) and
high-affinity transport (Km(fluorescein-methotrexate) 0.23 and 0.53 MUM, and
Km(fluorescein) 25.73 and 38.55 MUM for OATP1B1 and 1B3, respectively) of both
substrates. We found that sodium fluorescein is a general substrate of all human
OATPs: 1A2, 1B1, 1B3, 1C1, 2A1, 2B1, 3A1, 4A1, 4C1, 5A1 and 6A1, while
fluorescein-methotrexate is only transported by 1B1, 1B3, 1A2 and 2B1. Acidic
extracellular pH greatly facilitated fluorescein uptake by all OATPs, and new
molecular interactions were detected (between OATP2B1 and Imatinib, OATP3A1, 5A1
and 6A1 and estradiol 17-beta-d-glucuronide, and OATP1C1 and 4C1 and
prostaglandin E2). These studies demonstrate, for the first time, that the insect
cell system is suitable for the functional analysis of the entire human OATP
family, and for drug-OATP interaction screening.
PMID- 26415546
TI - Concepts of safety reporting.
PMID- 26415548
TI - Three cases of right frontal megalencephaly: Clinical characteristics and long
term outcome.
AB - AIM: To delineate the clinical and neuroimaging characteristics of localized
megalencephaly involving the right frontal lobe. METHOD: Data from three patients
aged 14-16 years at the last follow-up were retrospectively reviewed. RESULTS:
All the patients were normal on neurological examination with no signs of
hemiparesis. Enlargement of the right frontal lobe with increased volume of
subcortical and deep white matter, as well as thickening of the ipsilateral genu
of the corpus callosum was common. The onset of epilepsy was 4-7 years of age,
with seizure types of massive myoclonus in two and generalized tonic-clonic in
two, which could be eventually controlled by antiepileptics. Interictal
electroencephalography showed frontal alpha-like activity in one, and abundant
spike-wave complexes resulting in diffuse continuous spike-wave activity during
sleep in two patients even after suppression of clinical seizures. Psychomotor
development appeared unaffected or slightly delayed before the onset of epilepsy,
but became mildly disturbed during follow-up period of 7-11 years. CONCLUSION:
Certain patients with right frontal megalencephaly can present with a milder
epileptic and intellectual phenotype among those with localized megalencephaly
and holohemispheric hemimegalencephaly, whose characteristic as epileptic
encephalopathy was assumed from this study.
PMID- 26415547
TI - Targeted temperature management for acute encephalopathy in a Japanese secondary
emergency medical care hospital.
AB - BACKGROUND: The goals of this study, conducted in our secondary emergency care
hospital, were to assess the effectiveness of targeted temperature management
(TTM) for acute encephalopathy secondary to status epilepticus and to consider
appropriate adaptations for use of TTM in this setting. METHODS: Medical records
of patients admitted with acute encephalopathy to Hirakata City Hospital between
January 2010 and December 2014 were retrospectively reviewed. Cases treated with
TTM (36 degrees C) and methylprednisolone pulse (MP) therapy (TTM/MP) were
compared with those treated with conventional MP regarding clinical courses and
outcomes. RESULTS: In total, 20 children were retrospectively enrolled. In the
TTM/MP group (10 cases) all survived intact. In the MP group (10 cases), 4 cases
were left with neurological sequelae. Furthermore, in the TTM/MP group, the body
temperature dropped more quickly. For pediatricians in this secondary emergency
hospital, implementing the body temperature management system was not difficult.
There were no complications caused by hypothermia. DISCUSSION: Use of TTM as the
initial treatment for acute encephalopathy in the early-onset stage is possible
in a secondary emergency care hospital. However, some acute encephalopathy cases
are the so-called fulminant type; DIC or shock develops soon after onset and so
it is sometimes difficult to introduce TTM. Fulminant-type patients should be
transported to tertiary emergency care hospitals. Secondary emergency care
hospitals must carefully select cases for TTM, keeping the possibility of
transport to a tertiary emergency hospital in mind at all times.
PMID- 26415550
TI - Gender differences in the relationship between resting heart rate variability and
24-hour blood pressure variability.
AB - The study explored the relationship between time- and frequency-domain indices of
cardiac autonomic control and 24 h blood pressure variability (BPV) in a sample
of healthy men and women. Vagally mediated cardiac control was inversely related
to 24 h BPV, and measures of cardiac autonomic control were better predictors of
systolic BPV in men and better predictors of diastolic BPV in women. These
findings may help researchers to understand the disparity in cardiovascular
disease morbidity and mortality between men and women.
PMID- 26415551
TI - [Family access to Neonatal Intensive Care Units in Latin America: A reality to
improve].
AB - INTRODUCTION: Family access to NICUs has benefits for the newborn (NB) and
family, as the main way of humanised care. OBJECTIVE: To determine the current
state of parents and families access to NICUs in Latin America. METHODS: A cross
sectional study was conducted in 15 countries using two questionnaires: 1)
directed at head nurses with management and supervision activities, and 2) nurses
with care tasks. The features and modes of functioning were examined; the use
access guides, personal opinion on the rights to enter, risks, interference, or
collaboration as regards the patient, and nursing role in decisions. Nursing
leaders of each country identified contacts and obtained authorisation under the
regulations of each country. The responses were analysed centrally with the
participants remaining anonymous. RESULTS: Out of 640 questionnaires issued,
responses were received by 226 (35%). Among 52 NICU, 63% have a place for mothers
to stay (only 27% overnight), and in 31 (60%) there are notices with fixed
schedules for visiting the NB. Unrestricted access exists in only 19 NICU (36%),
but for siblings and grandparents it is more restricted (it is not possible in
29%). Among the 174 nurses that responded, 76% feel that mothers should always
have access, but these percentages decrease for fathers, siblings and
grandparents. A large majority (77%) believe that nursing staff would favour
access, and 35% would make it difficult. In addition, 48% believed that access
interferes with nursing care. care. CONCLUSION: A cultural change is needed in
the NICUs in Latin America in order to respect the rights of newborns and their
families during hospitalisation.
PMID- 26415549
TI - Randomised controlled trial of temoporfin photodynamic therapy plus chemotherapy
in nonresectable biliary carcinoma--PCS Nordic study.
AB - BACKGROUND: Photodynamic therapy (PDT) in combination with stent have shown
promising results in the treatment of biliary tract cancer (BTC) in patients not
suitable for surgery. Chemotherapy has been shown to improve survival in patients
with local advanced and metastatic BTC. MATERIAL AND METHODS: In the current
randomized trial the combination of chemotherapy and stent with and without
temoporfin (Foscan) photodynamic therapy (PDT), with a primary endpoint on
feasibility and safety, has been performed. Ten patients in each group. RESULTS:
No serious, acute procedure-related complication related to PDT or the treatment
combination was seen. The number of patients with cholangitis was equal in both
groups. In the PDT group--arm A--two patients had cutaneous erythema after sun
exposition, one of them with a localized blister. No neutropenic infection was
seen. Quality of Life (QoL) was similar in both treatment groups. Progression
free survival was numerically longer in the PDT group. CONCLUSION: The treatment
combination was feasible. There was no serious complication related to PDT or the
treatment combination. Number of cholangitis was equal in both groups, two
abscesses were observed in the PDT group. Progression free survival was
numerically longer in the PDT group.
PMID- 26415552
TI - Physapubescin B Exhibits Potent Activity against Human Prostate Cancer In Vitro
and In Vivo.
AB - The present data showed that a natural compound isolated from the plant Physalis
pubescens L. (Solanaceae), physapubescin B, exhibited antitumor activity against
prostate cancer in vitro and in vivo. Treating prostate cancer cells with
physapubescin B resulted in the accumulation of cells in the G2/M phase, which
was associated with reduced Cdc25C levels and increased levels of CyclinB1, P21
as well as p-Cdk1 (Tyr15). Additionally, reactive oxygen species (ROS) generation
was increased in physapubescin B-treated PC-3 cells. Furthermore, the
physapubescin B-induced decrease of Cdc25C protein expression together with the
G2/M phase cell cycle arrest were significantly abrogated by antioxidant NAC and
GSH. Our data also demonstrated that physapubescin B exhibited strong in vivo
antitumor efficacy in human prostate cancer PC3 xenograft. In conclusion, our
results provide clear evidence that physapubescin B exhibits antitumor activity
both in vitro and in vivo and deserves further development as an anticancer
agent.
PMID- 26415553
TI - Biomechanical influences on head posture and the respiratory movements of the
chest.
AB - PURPOSE: The head represents 6% of total body weight, therefore it can
significantly affect the biomechanics of human posture control, movements and
activities. When set out of vertical body axis, head position interferes with the
work of the other links in the kinematic chain. The aim of our study was to
evaluate the effect of head posture on the breathing activities of the chest.
MATERIAL AND METHODS: The research was conducted on a group of 65 patients (51
years +/- 9.8 years), including 48 women and 17 men. Head posture and chest
movements were assessed using a photogrammetric method. RESULTS: The results
confirmed the existence of a negative correlation between head position in the
sagittal plane and movements of lower ribs. Forward head posture resulted in
lower amplitude of costal arch motion: for the transverse plane Spearman's R =
0.296, for the frontal plane; -0.273, -0.289. Tilting the head in the frontal
plane also influenced the change in the biomechanics of breathing and contributed
to a reduction of respiratory movements of the lower ribs Spearman's R = -0.260.
CONCLUSIONS: Changing the position of the head causes disturbances in the three
dimensional shape of the chest and its respiratory movements.
PMID- 26415555
TI - Innocent Cardiac Murmur in Puppies: Prevalence, Correlation with Hematocrit, and
Auscultation Characteristics.
AB - BACKGROUND: The aims of this study were to establish the prevalence of innocent
cardiac murmurs in clinically healthy puppies, to investigate a possible
correlation between the presence of an innocent murmur and hematocrit, and to
describe the auscultation characteristics of innocent murmurs. HYPOTHESIS: Lower
hematocrit contributes to the genesis of innocent murmurs. ANIMALS: Five hundred
and eighty-four client-owned clinically healthy puppies, between 20 and 108 days
old. METHODS: Two cross-sectional surveys with a 1-year (n = 389 pups) pilot and
a half-year (n = 195 pups) principal study periods. Cardiac auscultation was
performed by a single, board-certified cardiologist. Hematocrit was measured with
an automatized hematology analyzer. Echocardiography was performed only on
puppies with a cardiac murmur in the principal study. RESULTS: In the pilot
study, 15% of the dogs had a murmur. Innocent murmur was diagnosed in 28% of the
195 dogs in the principal study. Innocent murmurs were systolic, mostly with a
musical character and with a maximal intensity of 2 of 6, and mostly with the
point of maximal intensity in the left cardiac base. The hematocrit was
significantly lower in the group with a murmur compared to the group without (P =
.023). CONCLUSIONS AND CLINICAL IMPORTANCE: Innocent murmur was a common finding
in puppies at the age when the first veterinary controls usually take place.
Physiologic anemia contributes to the genesis of innocent murmurs in puppies.
Rising hematocrit in growing puppies can explain the spontaneous disappearance of
innocent murmurs with aging. Hematocrit did not differentiate innocent murmurs
from abnormal murmurs.
PMID- 26415556
TI - Lower urinary tract symptoms among Caucasian-European men who have sex with men:
findings from a real-life survey.
AB - BACKGROUND: Prevalence of and severity of lower urinary tract symptoms (LUTS)
according to male sexual orientation have been scantly analysed. We aimed to
assess the prevalence and severity of LUTS in a cohort of Caucasian-European men
who have sex with men seeking medical help for uroandrologic reasons other than
LUTS. METHODS: Data from 949 consecutive individuals in an outpatient setting
were analysed. Severity of LUTS was measured with the International Prostate
Symptom Score (IPSS). Men with storage symptoms scored 1-3 and ? 4 (of 15), and
voiding symptoms scored 1-4 and ? 5 (of 20) were considered as having mild and
moderate-to-severe symptoms, respectively. For individual symptoms, patients with
scores ? 1 were deemed symptomatic (according to Apostolidis et al.(15)).
Descriptive statistics and logistic regression models tested the association
between LUTS and sexual orientation. RESULTS: Complete data were available for
213 (22.4%) men who have sex with men (MSM) and 736 (77.6%) heterosexuals (mean
age (s.d.): 41.0 (12.2) vs 39.9 (12.1) years). Compared with heterosexuals, MSM
reported higher rates of total IPSS scores suggestive of moderate (21.6% vs 20%)
and severe LUTS (3.8% vs 2.4%) (P=0.004). Similarly, MSM showed higher rates of
mild (48.8% vs 45.2%) and moderate-to-severe (39.4% vs 30.4%) storage symptoms
(all P<0.001), and of mild (45.1% vs 34.8%) and moderate-to-severe (20.2% vs
19.2%) voiding symptoms (all P<0.01). MSM status was an independent predictor of
mild voiding symptoms (odds ratio (OR): 1.40; P=0.004), moderate-to-severe
storage symptoms (OR: 1.40; P=0.04) and severe total IPSS (OR: 1.49; P=0.03),
after adjusting for other variables. CONCLUSIONS: These findings suggest a higher
prevalence and severity of LUTS in MSM compared with heterosexual men seeking
medical help for uroandrologic reasons other than LUTS.
PMID- 26415557
TI - Negative Impact of Unidirectional Host-versus-Graft Killer Cell Immunoglobulin
like Receptor Ligand Mismatch on Transplantation Outcomes after Unmanipulated
Haploidentical Peripheral Blood Stem Cell Transplantation for Acute Myeloid
Leukemia.
AB - This study explored the influence of mismatched inhibitory killer cell
immunoglobulin-like receptor (KIR) ligands on the outcome of haploidentical
transplantation using T cell-replete, granulocyte colony-stimulating factor
mobilized peripheral blood stem cells in adult patients with acute myeloid
leukemia (AML). Three groups were examined: unidirectional graft-versus-host KIR
ligand mismatched (GVH-KIR-MM; n = 33), bidirectional KIR ligand matched (KIR-M;
n = 41), and unidirectional host-versus-graft KIR ligand mismatched (HVG-KIR-MM;
n = 26). All recipients were treated with the same conditioning regimen (800 cGy
total body irradiation, fludarabine, busulfan, and antithymocyte globulin). After
a median follow-up of 26 months, the 2-year cumulative incidence of relapse was
significantly higher in HVG-KIR-MM (40.3% +/- 10.3%) versus others (18.9% +/-
4.8%, P = .044). In the standard-risk group, the 2-year disease-free survival
(DFS) was significantly lower in HVG-KIR-MM (51.8% +/- 11.2%) compared with GVH
KIR-MM (88% +/- 8.1%, P = .025). Multivariate analysis showed that HVG-KIR-MM was
significantly associated with higher relapse (hazard ratio [HR], 10.7; P = .002)
and lower DFS (HR, 3.4; P = .012). Subgroup analysis revealed increased DFS with
higher doses of CD3(+)CD8(+) and CD3(-)CD56(+) grafts in GVH-KIR-MM (90.9% +/-
8.7%, P = .006); there was no such effect in the other groups. Although our
conclusions are limited by the absence of donor KIR genotype data, our study
suggests unidirectional KIR ligand incompatibility in the host-versus-graft
vector has a detrimental effect on T cell-replete haploidentical transplantation
outcomes in adult patients with AML.
PMID- 26415558
TI - A Two-Step Haploidentical Versus a Two-Step Matched Related Allogeneic
Myeloablative Peripheral Blood Stem Cell Transplantation.
AB - Haploidentical stem cell transplantation (SCT) offers a transplantation option to
patients who lack an HLA-matched donor. We developed a 2-step approach to
myeloablative allogeneic hematopoietic stem cell transplantation for patients
with haploidentical or matched related (MR) donors. In this approach, the
lymphoid and myeloid portions of the graft are administered in 2 separate steps
to allow fixed T cell dosing. Cyclophosphamide is used for T cell tolerization.
Given a uniform conditioning regimen, graft T cell dose, and graft-versus-host
disease (GVHD) prophylaxis strategy, we compared immune reconstitution and
clinical outcomes in patients undergoing 2-step haploidentical versus 2-step MR
SCT. We retrospectively compared data on patients undergoing a 2-step
haploidentical (n = 50) or MR (n = 27) peripheral blood SCT for high-risk
hematological malignancies and aplastic anemia. Both groups received
myeloablative total body irradiation conditioning. Immune reconstitution data
included flow cytometric assessment of T cell subsets at day 28 and 90 after SCT.
Both groups showed comparable early immune recovery in all assessed T cell
subsets except for the median CD3/CD8 cell count, which was higher in the MR
group at day 28 compared with that in the haploidentical group. The 3-year
probability of overall survival was 70% in the haploidentical group and 71% in
the MR group (P = .81), while the 3-year progression-free survival was 68% in the
haploidentical group and 70% in the MR group (P = .97). The 3-year cumulative
incidence of nonrelapse mortality was 10% in the haploidentical group and 4% in
the MR group (P = .34). The 3-year cumulative incidence of relapse was 21% in the
haploidentical group and 27% in the MR group (P = .93). The 100-day cumulative
incidence of overall grades II to IV acute GVHD was higher in the haploidentical
group compared with that in the MR group (40% versus 8%, P < .001), whereas the
grades III and IV acute GVHD was not statistically different between both groups
(haploidentical, 6%; MR, 4%; P = .49). The cumulative incidence of
cytomegalovirus reactivation was also higher in the haploidentical group compared
to the MR group (haploidentical, 68%; MR, 19%; P < .001). There were no deaths
from GVHD in either group. Using an identical conditioning regimen, graft T cell
dose, and GVHD prophylaxis strategy, comparable early immune recovery and
clinical outcomes were observed in the 2-step haploidentical and MR SCT
recipients.
PMID- 26415554
TI - Expanding the biotechnology potential of lactobacilli through comparative
genomics of 213 strains and associated genera.
AB - Lactobacilli are a diverse group of species that occupy diverse nutrient-rich
niches associated with humans, animals, plants and food. They are used widely in
biotechnology and food preservation, and are being explored as therapeutics.
Exploiting lactobacilli has been complicated by metabolic diversity, unclear
species identity and uncertain relationships between them and other commercially
important lactic acid bacteria. The capacity for biotransformations catalysed by
lactobacilli is an untapped biotechnology resource. Here we report the genome
sequences of 213 Lactobacillus strains and associated genera, and their encoded
genetic catalogue for modifying carbohydrates and proteins. In addition, we
describe broad and diverse presence of novel CRISPR-Cas immune systems in
lactobacilli that may be exploited for genome editing. We rationalize the
phylogenomic distribution of host interaction factors and bacteriocins that
affect their natural and industrial environments, and mechanisms to withstand
stress during technological processes. We present a robust phylogenomic framework
of existing species and for classifying new species.
PMID- 26415559
TI - Umbilical Cord Blood Transplantation Outcomes in Acute Myelogenous
Leukemia/Myelodysplastic Syndrome Patients Aged >=70 Years.
AB - The maximum age of patients receiving allogeneic hematopoietic stem cell
transplantation (alloHCT) has been moving up over time. However, the availability
of a suitable HLA-matched sibling donor may limit access of this patient
population to alloHCT. We retrospectively investigated the outcomes of umbilical
cord blood transplantation (UCBT) after reduced-intensity conditioning regimens
in patients aged >=70 years with myelodysplastic syndrome (MDS) and acute
myelogenous leukemia (AML) between 2010 and 2014. During this period 70 patients
with AML/MDS were referred to our center for alloHCT consideration. Twenty-two
patients (33%) received alloHCT: 10 UCBT, 9 HLA full-matched sibling donor
transplantation, 2 haploidentical alloHCT, and 1 unrelated donor alloHCT. In
UCBT, cumulative incidences of nonrelapse mortality and relapse were 20% and 30%
at 2 years, respectively. The cumulative incidence of acute graft-versus-host
disease (GVHD) at day +100 and chronic GVHD at 2 years was 10%. Seven patients
had viral reactivation/infections. Rates of overall survival and disease-free
survival were 60% and 50% at 2 years, respectively. Moreover, these outcomes
seemed to be similar to that of patients aged 60 to 69 years receiving UCBT (n =
60) and patients aged >=70 years receiving HLA full-matched sibling donor
transplantation (n = 9). These results suggest that UCBT is feasible in selected
AML/MDS patients aged >=70 years. In fact, UCBT shortens the required time for an
unrelated donor search and thus increases the chance of proceeding with alloHCT,
which might contribute to higher rates of alloHCT in the referral group. Outcomes
of UCBT are promising; however, larger studies with a longer follow-up are
needed.
PMID- 26415560
TI - High Incidence of Afebrile Bloodstream Infection Detected by Surveillance Blood
Culture in Patients on Corticosteroid Therapy after Allogeneic Hematopoietic Stem
Cell Transplantation.
AB - Bloodstream infections (BSI) are still important complications after allogeneic
hematopoietic stem cell transplantation (allo-SCT). Patients who are receiving
corticosteroid therapy can develop BSI without fever. The utility of surveillance
blood cultures in these situations is controversial. We retrospectively analyzed
74 patients who received a corticosteroid consisting of >=.5 mg/kg prednisolone
or equivalent after allo-SCT. In principle, we performed surveillance blood
culture weekly for these patients. Sixteen patients (21.6%) developed definite
BSI. In a multivariate analysis, a myeloablative conditioning regimen, high-risk
disease status at allo-SCT, and the presence of a central venous catheter at the
initiation of corticosteroid therapy were identified as independent significant
risk factors for the development of definite BSI. At the first definite BSI
episode, 7 patients (46.7%) were afebrile and diagnosed by surveillance blood
culture. However, 6 of these 7 afebrile patients showed various signs that could
be attributed to infection at the time of positive blood culture. In conclusion,
patients receiving corticosteroid therapy after allo-SCT frequently develop
afebrile BSI. Although surveillance blood culture might be beneficial in these
situations, it also seems important to not miss the signs of BSI, even when
patients are afebrile.
PMID- 26415561
TI - On/off-switchable anti-neoplastic nanoarchitecture.
AB - Throughout the world, there are increasing demands for alternate approaches to
advanced cancer therapeutics. Numerous potentially chemotherapeutic compounds are
developed every year for clinical trial and some of them are considered as
potential drug candidates. Nanotechnology-based approaches have accelerated the
discovery process, but the key challenge still remains to develop therapeutically
viable and physiologically safe materials suitable for cancer therapy. Here, we
report a high turnover, on/off-switchable functionally popping reactive oxygen
species (ROS) generator using a smart mesoporous titanium dioxide popcorn (TiO2
Pops) nanoarchitecture. The resulting TiO2 Pops, unlike TiO2 nanoparticles (TiO2
NPs), are exceptionally biocompatible with normal cells. Under identical
conditions, TiO2 Pops show very high photocatalytic activity compared to TiO2
NPs. Upon on/off-switchable photo activation, the TiO2 Pops can trigger the
generation of high-turnover flash ROS and can deliver their potential anticancer
effect by enhancing the intracellular ROS level until it crosses the threshold to
open the 'death gate', thus reducing the survival of cancer cells by at least six
times in comparison with TiO2 NPs without affecting the normal cells.
PMID- 26415562
TI - Optical Limiting and Theoretical Modelling of Layered Transition Metal
Dichalcogenide Nanosheets.
AB - Nonlinear optical property of transition metal dichalcogenide (TMDC) nanosheet
dispersions, including MoS2, MoSe2, WS2, and WSe2, was performed by using Z-scan
technique with ns pulsed laser at 1064 nm and 532 nm. The results demonstrate
that the TMDC dispersions exhibit significant optical limiting response at 1064
nm due to nonlinear scattering, in contrast to the combined effect of both
saturable absorption and nonlinear scattering at 532 nm. Selenium compounds show
better optical limiting performance than that of the sulfides in the near
infrared. A liquid dispersion system based theoretical modelling is proposed to
estimate the number density of the nanosheet dispersions, the relationship
between incident laser fluence and the size of the laser generated micro-bubbles,
and hence the Mie scattering-induced broadband optical limiting behavior in the
TMDC dispersions.
PMID- 26415564
TI - Diffuse cavernous hemangioma of the rectum: case report and literature review.
PMID- 26415563
TI - Adult autologous mesenchymal stem cells for the treatment of suspected non
infectious inflammatory diseases of the canine central nervous system: safety,
feasibility and preliminary clinical findings.
AB - BACKGROUND: Non-infectious inflammatory diseases of the canine central nervous
system (CNS) are common idiopathic disorders grouped under the term
meningoencephalomyelitis of unknown origin (MUO). Ante mortem diagnosis is
achieved via assessment of clinical signs, magnetic resonance imaging (MRI), and
cerebrospinal fluid (CSF) analysis, but the definitive diagnosis needs
histopathological examination. MUO are mostly considered as autoimmune CNS
disorders, so that suppressing the immune reaction is the best management method
for patients. Mesenchymal stem cells (MSCs) are under investigation to treat
autoimmune and degenerative disorders due to their immunomodulatory and
regenerative properties. This study aims to verify the safety, feasibility, and
efficacy of MSCs treatment in canine idiopathic autoimmune inflammatory disorders
of the CNS. METHODS: Eight dogs presented with acute onset and rapid progression
of multifocal neurological signs were selected to the study. In all patients'
physical and neurological examinations, MRI and CSF analyses were performed.
Clinical diagnosis in all cases was MUO. All selected dogs responded initially to
immunosuppressive drugs (prednisone and a combination of prednisolone and
cytosine arabinoside) but developed undesirable side effects. For all eight dogs,
the owners considered euthanasia but accepted cell therapy as a last possibility.
Autologous bone marrow MSCs (BMMSCs), isolated, cultured, and expanded, were
administered by intrathecal (IT) injection in the cisterna magna intravenously
(IV) and by intra-arterial (IA) injection in the right carotid artery. Adverse
effects and clinical response were monitored for 6 months up to 2-year follow-up.
RESULTS: The use of autologous BMMSCs in dogs with MUO was safe for IT, IV, and
IA injections. No major short- or long-term adverse effects were registered. All
the dogs presented early improvement in their general and neurological
conditions, with particular effect on cervical pain. The group of dogs treated by
IT+IA administration showed a shorter time of reaction to therapy compared to the
group treated by IT+IV administration. CONCLUSIONS: MSCs treatment in dogs
affected by MOU is safe and feasible. A larger group of dogs is needed to confirm
these results as well as CNS histology in order to better understand the
underlying mechanisms.
PMID- 26415565
TI - Factors associated with reclassification of hyperplastic polyps after
pathological reassessment from screening and surveillance colonoscopies.
AB - INTRODUCTION: A substantial interobserver variation in the differential diagnosis
of hyperplastic polyps (HPs) and sessile or traditional serrated adenomas
(SSAs/TSAs) has been described. METHODS: The aim of this study is to determine
the magnitude of reclassification of HPs and associated factors after
pathological reassessment of specimens from screening and surveillance
colonoscopies, and to estimate its consequences for follow-up recommendations.
RESULTS: Among 1694 screening and surveillance colonoscopies, a total of 536
polyps were initially diagnosed as HPs and remained unchanged in 88.5% (n = 474),
whereas 7.6 (n = 41) and 1.1% (n = 6) were reclassified as SSA and TSA,
respectively. Compared to definite HPs, SSAs were found more frequently in men
than in women (82.9 vs. 61.2%, p < 0.05), and in individuals >=65.0 years (51.2
vs. 31.6%, p = 0.05). Also, more SSAs were >5 mm in size (36.6 vs. 6.3%, p <
0.05) and were localized in the proximal colon (31.7 vs. 11.8%, p < 0.05). In a
mixed model analysis, age >=65.0 years (OR 4.13, 95% CI 1.22-14.2), snare
polypectomy (OR 23.6, 95% CI 4.86-115), and coincident advanced adenomas (OR
7.56, 95% CI 1.31-43.5) were significantly (p < 0.05) associated with
reclassification to SSAs. Only 0.53% of patients had received false
recommendations for follow-up visits based on the incorrect HP diagnosis. A
c.1799T>A, p.V600E BRAF mutation was detected in 21.9 % (n = 9) of reclassified
SSAs. CONCLUSION: Considering these factors may be helpful in serrated lesions
that are difficult to allocate. Incorrect recommendations regarding control
colonoscopy intervals due to misdiagnosed HPs can explain only a small fraction
of interval colorectal cancers.
PMID- 26415567
TI - Of ATPase activity, cellular energy distribution, and linking depolarization and
division.
PMID- 26415566
TI - Further studies of the down-regulation by Factor I of the C3b feedback cycle
using endotoxin as a soluble activator and red cells as a source of CR1 on sera
of different complotype.
AB - In this paper we have extended our earlier studies of the action of increasing
Factor I concentration on complement activation by using a soluble activator,
lipopolysaccharide (LPS) endotoxin, and using human erythrocytes as a source of
CR1 - the co-factor needed for the final clip of iC3b to C3dg by Factor I. Using
this more physiological system, the results show that we can predict that a quite
modest increase in Factor I concentration - 22 ug/ml of extra Factor I - will
convert the activity of the highest risk sera to those of the lowest risk.
Preliminary experiments have been performed with erythrocytes allotyped for CR1
number. While we have not been able to perform an adequate study of their co
factor activities in our assays, preliminary experiments suggest that when Factor
I levels are increased the difference produced by different allotypes of red
cells is largely overcome. This suggests that in patients with paroxysmal
nocturnal haemoglobinuria (PNH) treated with eculizumab, additional treatment
with Factor I may be very useful in reducing the need for blood transfusion. We
have also explored the age-related allele frequency for the two polymorphisms of
Factor H and the polymorphism of C3. In our population, unlike the 1975 study, we
found no age variation in the allele frequency in these polymorphisms. This may,
however, reflect that the Cambridge BioResource volunteers do not include many
very young or very elderly patients, and in general comprise a population not
greatly at risk of death from infectious disease.
PMID- 26415568
TI - Diffusion of myosin light chain kinase on actin: A mechanism to enhance myosin
phosphorylation rates in smooth muscle.
AB - Smooth muscle myosin (SMM) light chain kinase (MLCK) phosphorylates SMM, thereby
activating the ATPase activity required for muscle contraction. The abundance of
active MLCK, which is tightly associated with the contractile apparatus, is low
relative to that of SMM. SMM phosphorylation is rapid despite the low ratio of
MLCK to SMM, raising the question of how one MLCK rapidly phosphorylates many SMM
molecules. We used total internal reflection fluorescence microscopy to monitor
single molecules of streptavidin-coated quantum dot-labeled MLCK interacting with
purified actin, actin bundles, and stress fibers of smooth muscle cells.
Surprisingly, MLCK and the N-terminal 75 residues of MLCK (N75) moved on actin
bundles and stress fibers of smooth muscle cell cytoskeletons by a random one
dimensional (1-D) diffusion mechanism. Although diffusion of proteins along
microtubules and oligonucleotides has been observed previously, this is the first
characterization to our knowledge of a protein diffusing in a sustained manner
along actin. By measuring the frequency of motion, we found that MLCK motion is
permitted only if acto-myosin and MLCK-myosin interactions are weak. From these
data, diffusion coefficients, and other kinetic and geometric considerations
relating to the contractile apparatus, we suggest that 1-D diffusion of MLCK
along actin (a) ensures that diffusion is not rate limiting for phosphorylation,
(b) allows MLCK to locate to areas in which myosin is not yet phosphorylated, and
(c) allows MLCK to avoid getting "stuck" on myosins that have already been
phosphorylated. Diffusion of MLCK along actin filaments may be an important
mechanism for enhancing the rate of SMM phosphorylation in smooth muscle.
PMID- 26415569
TI - A novel Ca2+-feedback mechanism extends the operating range of mammalian rods to
brighter light.
AB - Sensory cells adjust their sensitivity to incoming signals, such as odor or
light, in response to changes in background stimulation, thereby extending the
range over which they operate. For instance, rod photoreceptors are extremely
sensitive in darkness, so that they are able to detect individual photons, but
remain responsive to visual stimuli under conditions of bright ambient light,
which would be expected to saturate their response given the high gain of the rod
transduction cascade in darkness. These photoreceptors regulate their sensitivity
to light rapidly and reversibly in response to changes in ambient illumination,
thereby avoiding saturation. Calcium ions (Ca2+) play a major role in mediating
the rapid, subsecond adaptation to light, and the Ca2+-binding proteins GCAP1 and
GCAP2 (or guanylyl cyclase-activating proteins [GCAPs]) have been identified as
important mediators of the photoreceptor response to changes in intracellular
Ca2+. However, mouse rods lacking both GCAP1 and GCAP2 (GCAP-/-) still show
substantial light adaptation. Here, we determined the Ca2+ dependency of this
residual light adaptation and, by combining pharmacological, genetic, and
electrophysiological tools, showed that an unknown Ca2+-dependent mechanism
contributes to light adaptation in GCAP-/- mouse rods. We found that mimicking
the light-induced decrease in intracellular [Ca2+] accelerated recovery of the
response to visual stimuli and caused a fourfold decrease of sensitivity in GCAP
/- rods. About half of this Ca2+-dependent regulation of sensitivity could be
attributed to the recoverin-mediated pathway, whereas half of it was caused by
the unknown mechanism. Furthermore, our data demonstrate that the feedback
mechanisms regulating the sensitivity of mammalian rods on the second and
subsecond time scales are all Ca2+ dependent and that, unlike salamander rods,
Ca2+-independent background-induced acceleration of flash response kinetics is
rather weak in mouse rods.
PMID- 26415571
TI - A sequence of basic residues in the porcine circovirus type 2 capsid protein is
crucial for its co-expression and co-localization with the replication protein.
AB - Porcine circovirus type 2 (PCV2) encodes two major proteins: the replication
protein (Rep) and the capsid protein (Cap). Cap displays a conserved stretch of
basic residues situated on the inside of the capsid, whose role is so far
unknown. We used a reverse-genetics approach to investigate its function and
found that mutations in these amino acids hindered Cap mRNA translation and
hampered Cap/Rep co-localization, yielding unfit viruses. Intriguingly, co
transfection with a WT PCV2 of a different genotype partially rescued mutant Cap
expression, showing the importance of this basic pattern for efficient
translation of Cap mRNA into protein. Our results show that Cap and Rep are
expressed independently of each other, and that this amino acid sequence of Cap
is vital for virus propagation. This study provides a method for studying unfit
PCV2 virions and offers new insights into the intracellular modus vivendi of
PCV2.
PMID- 26415570
TI - A chimeric prokaryotic pentameric ligand-gated channel reveals distinct pathways
of activation.
AB - Recent high resolution structures of several pentameric ligand-gated ion channels
have provided unprecedented details of their molecular architecture. However, the
conformational dynamics and structural rearrangements that underlie gating and
allosteric modulation remain poorly understood. We used a combination of
electrophysiology, double electron-electron resonance (DEER) spectroscopy, and x
ray crystallography to investigate activation mechanisms in a novel functional
chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi
ligand-gated ion channel, which is activated by primary amines, and the
transmembrane domain of Gloeobacter violaceus ligand-gated ion channel, which is
activated by protons. We found that the chimera was independently gated by
primary amines and by protons. The crystal structure of the chimera in its
resting state, at pH 7.0 and in the absence of primary amines, revealed a closed
pore conformation and an ECD that is twisted with respect to the transmembrane
region. Amine- and pH-induced conformational changes measured by DEER
spectroscopy showed that the chimera exhibits a dual mode of gating that
preserves the distinct conformational changes of the parent channels.
Collectively, our findings shed light on both conserved and divergent features of
gating mechanisms in this class of channels, and will facilitate the design of
better allosteric modulators.
PMID- 26415572
TI - Phytogenic pigments in animal nutrition: potentials and risks.
AB - Phytogenic pigments are secondary plant compounds responsible for coloring
effects in plant tissues. In particular, phenolic flavonoids and terpenoid
carotenoids, but also rare compounds like curcumin and betalain, form this group
of biochemical agents used in animal nutrition. From the perspective of
ecological mutuality between plants and animals, these compounds are of crucial
importance because they serve as visual attraction for herbivores but also signal
nutritional and/or health-promoting values. This review focuses on the properties
of phytogenic pigments which are likely to impact feed intake and preferences of
livestock. Also natural prophylactic and/or therapeutic properties and, in
particular, the potential of pigments to enhance quality and health value of
animal products for human consumption are important issues. Nevertheless,
reasonable limits of use due to possible adverse indications have been suggested
recently. Pathways of digestion, metabolism and excretion in animals play a
crucial role not only in the evaluation of effectiveness but also in the
prediction of potential risks for human consumption. The popularity of natural
feed additives is growing; therefore, more research work is needed to better
understand metabolic pathways in the animal's body and to better estimate the
potentials and risks of pigmenting plant compounds used in animal nutrition.
PMID- 26415574
TI - Influenza Plasmid DNA Vaccines: Progress and Prospects.
AB - Current influenza vaccines have long been used to fight flu infectious; however,
recent advances highlight the importance of produce new alternatives. Even though
traditional influenza vaccines are safe and usually effective, they need to be
uploaded every year to anticipate circulating flu viruses. This limitation
together with the use of embryonated chicken eggs as the substrate for vaccine
production, is time-consuming and could involve potential biohazards in growth of
new virus strains. Plasmid DNA produced by prokaryote microorganisms and encoding
foreign proteins had emerged as a promising therapeutic tool. This technology
allows the expression of a gene of interest by eukaryotic cells in order to
induce protective immune responses against the pathogen of interest. In this
review, we discuss the strategies to choose the best DNA vaccine to be applied in
the treatment and prevention of influenza. Specifically, we give an update of
influenza DNA vaccines developments, all involved techniques, their main
characteristics, applicability and technical features to obtain the best option
against influenza infections.
PMID- 26415573
TI - Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect.
AB - Duchenne muscular dystrophy (DMD) is characterized by the loss of a functional
dystrophin protein; the muscles of DMD patients progressively degenerate as a
result of mechanical stress during contractions, and the condition eventually
leads to premature death. By means antisense oligonucleotides (AONs), it is
possible to modulate pre-mRNA splicing eliminating mutated exons and restoring
dystrophin open reading frame. To overcome the hurdles in using AONs for
therapeutic interventions, we exerted engineered human DMD stem cells with a
lentivirus, which permanently and efficiently delivered the cloned AONs. Here we
describe for the first time the exosome-mediated release of AONs from engineered
human DMD CD133+ stem cells allowing the rescue of murine dystrophin expression.
Finally, upon release, AONs could be internalized by host cells suggesting a
potential role of exosomes acting as vesicular carriers for DMD gene therapy.
PMID- 26415575
TI - Lentiviral-Mediated Gene Therapy in Fanconi Anemia-A Mice Reveals Long-Term
Engraftment and Continuous Turnover of Corrected HSCs.
AB - Fanconi anemia is a DNA repair-deficiency syndrome mainly characterized by cancer
predisposition and bone marrow failure. Trying to restore the hematopoietic
function in these patients, lentiviral vector-mediated gene therapy trials have
recently been proposed. However, because no insertional oncogenesis studies have
been conducted so far in DNA repair-deficiency syndromes such as Fanconi anemia,
we have carried out a genome-wide screening of lentiviral insertion sites after
the gene correction of Fanca(-/-) hematopoietic stem cells (HSCs), using LAM-PCR
and 454-pyrosequencing. Our studies first demonstrated that transduction of
Fanca(-/-) HSCs with a lentiviral vector designed for clinical application
efficiently corrects the phenotype of Fanconi anemia repopulating cells without
any sign of toxicity. The identification of more than 6,500 insertion sites in
primary and secondary recipients showed a polyclonal pattern of reconstitution,
as well as a continuous turnover of corrected Fanca(-/-) HSC clones, without
evidences of selection towards specific common integration sites. Taken together
our data show, for the first time in a DNA repair-deficiency syndrome, that
lentiviral vector-mediated gene therapy efficiently corrects the phenotype of
affected HSCs and promotes a healthy pattern of clonal turnover in vivo. These
studies will have a particular impact in the development of new gene therapy
trials in patients affected by DNA repair syndromes, particularly in Fanconi
anemia.
PMID- 26415576
TI - Contemporary Animal Models For Human Gene Therapy Applications.
AB - Over the past three decades, gene therapy has been making considerable progress
as an alternative strategy in the treatment of many diseases. Since 2009, several
studies have been reported in humans on the successful treatment of various
diseases. Animal models mimicking human disease conditions are very essential at
the preclinical stage before embarking on a clinical trial. In gene therapy, for
instance, they are useful in the assessment of variables related to the use of
viral vectors such as safety, efficacy, dosage and localization of transgene
expression. However, choosing a suitable disease-specific model is of paramount
importance for successful clinical translation. This review focuses on the animal
models that are most commonly used in gene therapy studies, such as murine,
canine, non-human primates, rabbits, porcine, and a more recently developed
humanized mice. Though small and large animals both have their own pros and cons
as disease-specific models, the choice is made largely based on the type and
length of study performed. While small animals with a shorter life span could be
well-suited for degenerative/aging studies, large animals with longer life span
could suit longitudinal studies and also help with dosage adjustments to maximize
therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have
gained interest in the study of human tissues or cells, thereby providing a more
reliable understanding of therapeutic interventions. Thus, animal models are of
great importance with regard to testing new vector technologies in vivo for
assessing safety and efficacy prior to a gene therapy clinical trial.
PMID- 26415578
TI - TREAT: tamper-resistant envelope allocation technique for a multisite study.
PMID- 26415577
TI - Field-wide meta-analyses of observational associations can map selective
availability of risk factors and the impact of model specifications.
AB - OBJECTIVES: Instead of evaluating one risk factor at a time, we illustrate the
utility of "field-wide meta-analyses" in considering all available data on all
putative risk factors of a disease simultaneously. STUDY DESIGN AND SETTING: We
identified studies on putative risk factors of pterygium (surfer's eye) in
PubMed, EMBASE, and Web of Science. We mapped which factors were considered,
reported, and adjusted for in each study. For each putative risk factor, four
meta-analyses were done using univariate only, multivariate only, preferentially
univariate, or preferentially multivariate estimates. RESULTS: A total of 2052
records were screened to identify 60 eligible studies reporting on 65 putative
risk factors. Only 4 of 60 studies reported both multivariate and univariate
regression analyses. None of the 32 studies using multivariate analysis adjusted
for the same set of risk factors. Effect sizes from different types of regression
analyses led to significantly different summary effect sizes (P-value < 0.001).
Observed heterogeneity was very high for both multivariate (median I(2), 76.1%)
and univariate (median I(2), 85.8%) estimates. No single study investigated all
11 risk factors that were statistically significant in at least one of our meta
analyses. CONCLUSION: Field-wide meta-analyses can map availability of risk
factors and trends in modeling, adjustments and reporting, as well as the impact
of differences in model specification.
PMID- 26415579
TI - Fermi level engineering of topological insulator films by tuning the substrates.
AB - The Fermi level of the topological insulators (TIs) Bi2Se3 and Bi2Te3 is usually
well above the Dirac points, which is ascribed to the intrinsic donor defects,
such as antisites and anion vacancies. We show here by first-principles
calculations that the substrates can modulate the Fermi level of TIs
considerably. It is found that in Bi2Se3/graphene and Bi2Te3/Si(1 1 1), the
substrates play the role of electron donor due to their lower workfunctions and
push up the Fermi level of the TIs. Thicker TI films are found to have larger
density of states and hence the charge transferred to TI leads to a smaller Fermi
level shift, in good agreement with experiments. We propose to use high
workfunction substrates to counterbalance the upward shift of the Fermi level due
to the donor defects. Our calculations found that the fluorinated substrates F
graphene and F-Si(1 1 1) have very high workfunction and become electron
acceptors, leading to a downward shift of the Fermi level of TIs.
PMID- 26415580
TI - Iron(II) spin crossover complexes with diaminonaphthalene-based Schiff base-like
ligands: mononuclear complexes.
AB - The synthesis of new Schiff base-like ligands with extended pi-system and their
iron complexes is described. Some of the iron(ii) complexes with N-heterocycles
as axial ligands show spin crossover behaviour. The influence of the extended
aromatic system on cooperative interactions is investigated by single crystal X
ray structure analysis, X-ray powder diffraction, and magnetic measurements. A
combination of C-Hpi and C-HO interactions is made responsible for up to 10 K
wide thermal hysteresis loops.
PMID- 26415581
TI - Response inhibition and interference control in patients with bipolar I disorder
and first-degree relatives.
AB - OBJECTIVES: The current study aimed to assess both response inhibition (RI) and
interference control (IC) in euthymic patients with bipolar disorder (BD-Ps) as
well as asymptomatic first-degree relatives (BD-Rs) and healthy controls (HCs) in
order to evaluate trait-as opposed to illness-associated features of these
components. METHODS: BD-Ps (n = 35) who had been in the euthymic state for at
least six months, BD-Rs (n = 30), and HCs (n = 33) completed a Stop-Signal Task
(SST) and Stroop Task to assess RI and IC, respectively. Groups were compared on
the stop-signal reaction time (SSRT), stop-signal delay (SSD), mean reaction time
on go trials (go-RT), Stroop interference score (S-interference), and number of
errors on the color-word-naming trial (S-error). Associations between the
patient's clinical features and RI and IC, between the patient's treatment and RI
and IC, and between RI and IC in each group were investigated. RESULTS: BD-Ps and
BD-Rs had significantly shorter go-RT and SSD, and longer SSRT compared to HCs,
with these scores being similar between the BD-Ps and BD-Rs. Also, both BD-Ps and
BD-Rs made significantly more S-errors than HCs, whereas, the S-interference
score was not significantly different between groups. There were no significant
correlations between Stroop Task and SST scores within each group, nor between
clinical features or treatment variables and RI and IC in BD-Ps. CONCLUSIONS:
Overall, impairment in RI and IC (only on S-error score) was present in both
patients and relatives. The persistence of these deficits in the absence of mood
symptoms suggests that these features may represent candidate endophenotypes for
bipolar disorder.
PMID- 26415582
TI - Editorial: Television sets and traumatic brain injury.
PMID- 26415583
TI - Performance comparison of various feature detector-descriptors and temporal
models for video-based assessment of laparoscopic skills.
AB - BACKGROUND: Despite the significant progress in hand gesture analysis for
surgical skills assessment, video-based analysis has not received much attention.
In this study we investigate the application of various feature detector
descriptors and temporal modeling techniques for laparoscopic skills assessment.
METHODS: Two different setups were designed: static and dynamic video-histogram
analysis. Four well-known feature detection-extraction methods were investigated:
SIFT, SURF, STAR-BRIEF and STIP-HOG. For the dynamic setup two temporal models
were employed (LDS and GMMAR model). Each method was evaluated for its ability to
classify experts and novices on peg transfer and knot tying. RESULTS: STIP-HOG
yielded the best performance (static: 74-79%; dynamic: 80-89%). Temporal models
had equivalent performance. Important differences were found between the two
groups with respect to the underlying dynamics of the video-histogram sequences.
CONCLUSIONS: Temporal modeling of feature histograms extracted from laparoscopic
training videos provides information about the skill level and motion pattern of
the operator. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26415584
TI - Pruritus in psoriasis: An update.
AB - BACKGROUND AND OBJECTIVE: Psoriasis is one of the most common chronic
inflammatory skin diseases, found in about 1-3% of the general population.
Pruritus affects about 60-90% of patients with psoriasis. The aim of this review
was to summarize current knowledge about the pathogenesis and treatment of this
symptom in psoriasis patients. RESULTS: Majority of psoriatic patients consider
pruritus as the most bothersome symptom. The pathogenesis of pruritus is still
unknown but the major concept of its origin is focused on neurogenic
inflammation. Possible itch mediators include neuropeptides released from dermal
nerve endings upon various stimuli, which were found to be abnormally expressed
in itchy psoriatic plaques. Another important phenomenon supporting the idea of
neurogenic inflammation as a key player in pruritus accompanying psoriasis is
abnormal innervations of psoriatic skin. Possibly increased innervation density
in psoriasis may decrease the threshold for pruritic stimuli. It is also
suggested that pruritus in psoriasis might be related to abnormal functioning of
the peripheral opioid system. Despite the high frequency of pruritus in
psoriasis, to date there is no single antipruritic therapy dedicated specifically
to treat itch in this disease. CONCLUSIONS: Neurogenic inflammation seems to be
important for itchiness in psoriasis. Treatment of pruritus in patients with
psoriasis should be directed towards the resolution of skin lesions, as disease
remission usually is linked with pruritus relief.
PMID- 26415586
TI - A water soluble glucopyranosyl conjugate as a selective and reactive probe for
cysteine in a buffer and its application to living cells.
AB - A water soluble and biocompatible glucopyranosyl conjugate (L) has been
synthesized and characterized by various techniques. The L has been employed to
recognize Cys selectively among the naturally occurring amino acids in HEPES
buffer at physiological pH. A minimum detection limit of 2.5 * 10(-7) M was shown
by L for Cys in the buffer at pH = 7.4. The reactivity of L towards biological
thiols as demonstrated by emission and absorption is supported by the observed
increase in the fluorescence intensity; however, Cys shows a maximum increase
owing to its better nucleophilicity. The reactivity of Cys on L is demonstrated
by (1)H NMR, ESI MS, emission and absorption spectroscopy, and the formation of
the binary complex was supported by ESI MS. The control molecular study revealed
the necessity of the glyco-moiety to bring water solubility and biological
adaptability. The cellular studies support that the conjugate L is biologically
adaptable and shows effective intracellular fluorescence emission upon reacting
with intracellular thiols.
PMID- 26415585
TI - Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK
STAT pathway in Sezary syndrome.
AB - Sezary syndrome (SS) is an aggressive leukaemia of mature T cells with poor
prognosis and limited options for targeted therapies. The comprehensive genetic
alterations underlying the pathogenesis of SS are unknown. Here we integrate
whole-genome sequencing (n=6), whole-exome sequencing (n=66) and array
comparative genomic hybridization-based copy-number analysis (n=80) of primary SS
samples. We identify previously unknown recurrent loss-of-function aberrations
targeting members of the chromatin remodelling/histone modification and trithorax
families, including ARID1A in which functional loss from nonsense and frameshift
mutations and/or targeted deletions is observed in 40.3% of SS genomes. We also
identify recurrent gain-of-function mutations targeting PLCG1 (9%) and JAK1,
JAK3, STAT3 and STAT5B (JAK/STAT total ~11%). Functional studies reveal
sensitivity of JAK1-mutated primary SS cells to JAK inhibitor treatment. These
results highlight the complex genomic landscape of SS and a role for inhibition
of JAK/STAT pathways for the treatment of SS.
PMID- 26415587
TI - Seminal fluid factors regulate activin A and follistatin synthesis in female
cervical epithelial cells.
AB - Seminal fluid induces pro-inflammatory cytokines and elicits an inflammation-like
response in the cervix. Here, Affymetrix microarray and qPCR was utilised to
identify activin A (INHBA) and its inhibitor follistatin (FST) amongst the
cytokines induced by seminal plasma in Ect1 ectocervical epithelial cells, and a
similar response was confirmed in primary ectocervical epithelial cells. TGFB is
abundant in seminal plasma and all three TGFB isoforms induced INHBA in Ect1 and
primary cells, and neutralisation of TGFB in seminal plasma suppressed the INHBA
response. Bacterial lipopolysaccharide in seminal plasma also elicited INHBA, but
potently suppressed FST production. There was moderate reciprocal inhibition
between FST and INHBA, and cross-attenuating effects were seen. These data
identify TGFB and potentially LPS as factors mediating seminal plasma-induced
INHBA synthesis in cervical cells. INHBA and FST induced by seminal fluid in
cervical tissues may thus contribute to regulation of the post-coital response in
women.
PMID- 26415588
TI - Detection of metabolites discriminating subtypes of thyroid cancer: Molecular
profiling of FFPE samples using the GC/MS approach.
AB - One of the critical issues in thyroid cancer diagnostic is differentiation
between follicular adenoma, follicular carcinoma and the follicular variant of
papillary carcinoma, which in some cases is not possible based on
histopathological features only. In this paper we performed molecular profiling
of thyroid tissue aiming to identify metabolites characteristic for different
types of thyroid cancer. FFPE tissue specimens were analysed from 5 different
types of thyroid malignancies (follicular, papillary/classical variant,
papillary/follicular variant, medullary and anaplastic cancers), benign
follicular adenoma and normal thyroid. Extracted metabolites were identified and
semi-quantified using the GC/MS approach. There were 28 metabolites identified,
whose abundances were significantly different among different types of thyroid
tumours, including lipids, carboxylic acids, and saccharides. We concluded, that
multi-component metabolome signature could be used for classification of
different subtypes of follicular thyroid lesions. Moreover, potential
applicability of the GC/MS-based analysis of FFPE tissue samples in diagnostics
of thyroid cancer has been proved.
PMID- 26415589
TI - Brain lipid sensing and the neural control of energy balance.
AB - Fatty acid (FA) -sensitive neurons are present in the brain, especially the
hypothalamus, and play a key role in the neural control of energy and glucose
homeostasis including feeding behavior, secretion insulin and action.
Subpopulations of neurons in the arcuate and ventromedial hypothalamic nuclei are
selectively either activated or inhibited by FA. Molecular effectors of these FA
effects include ion channels such as chloride, potassium or calcium. In addition,
at least half of the responses in the hypothalamic ventromedial FA neurons are
mediated through interaction with the FA translocator/receptor, FAT/CD36, that
does not require metabolism to activate intracellular signaling downstream.
Recently, an important role of lipoprotein lipase in FA detection has also been
demonstrated not only in the hypothalamus, but also in the hippocampus and
striatum. Finally, FA could overload energy homeostasis via increased
hypothalamic ceramide synthesis which could, in turn, contribute to the
pathogenesis of diabetes of obesity and/or type 2 in predisposed individuals by
disrupting the endocrine signaling pathways of insulin and/or leptin.
PMID- 26415590
TI - Fibroblast growth factor-21, energy balance and obesity.
AB - Fibroblast growth factor (FGF)-21 is an endocrine member of the FGF family with
healthy effects on glucose and lipid metabolism. FGF21 reduces glycemia and
lipidemia in rodent models of obesity and type 2 diabetes. In addition to its
effects improving insulin sensitivity, FGF21 causes weight loss by increasing
energy expenditure. Activation of the thermogenic activity of brown adipose
tissue and promotion of the appearance of the so-called beige/brite type of brown
adipocytes in white fat are considered the main mechanisms underlying the leaning
effects of FGF21. Paradoxically, however, obesity in rodents and humans is
characterized by high levels of FGF21 in the blood. Some degree of resistance to
the actions of FGF21 has been proposed as part of the endocrine alterations in
obesity. The resistance in adipose tissue from obese rodents and patients is
likely attributable to abnormally low levels of the FGF co-receptor beta-Klotho,
required for FGF21 cellular action. However, native FGF21 and FGF21 derivatives
retain their healthy metabolic and weight-loss effects when used as
pharmacological agents to treat obese rodents and humans. FGF21 derivatives or
molecules mimicking FGF21 action appear to be interesting candidates for the
development of novel anti-obesity drugs designed to increase energy expenditure.
PMID- 26415591
TI - Steroid hormone influence on melanomagenesis.
AB - Disparities in the prognosis and incidence of melanoma between male and female
patients have led clinicians to explore the influence of steroid hormones on the
development and progression of this malignancy. A better understanding of the
disparities of melanoma behavior between sexes and ages could lead to improved
prevention and treatment options. There are multiple themes in the literature
that unify the physiologic functions of estrogen and androgen receptors; herein
we discuss and map their pathways. Overall, it is important to understand that
the differences in melanoma behavior between the sexes are multifactorial and
likely involve interactions between the immune system, endocrine system, and
environment, namely UV-radiation. Melanoma deserves a spot among hormone
sensitive tumors, and if tamoxifen is re-introduced for future therapy, tissue
ratios of estrogen receptors should be obtained beforehand to assess their
therapeutic predictive value. Because androgens, estrogens, and their receptors
are involved in signaling of commonly mutated melanoma pathways, potential
synergistic properties of the recently developed molecular kinase inhibitors that
target those pathways may exist.
PMID- 26415592
TI - Modeling of electrochemical double layers in thermodynamic non-equilibrium.
AB - We consider the contact between an electrolyte and a solid electrode. At first we
formulate a thermodynamic consistent model that resolves boundary layers at
interfaces. The model includes charge transport, diffusion, chemical reactions,
viscosity, elasticity and polarization under isothermal conditions. There is a
coupling between these phenomena that particularly involves the local pressure in
the electrolyte. Therefore the momentum balance is of major importance for the
correct description of the boundary layers. The width of the boundary layers is
typically very small compared to the macroscopic dimensions of the system. In the
second step we thus apply the method of asymptotic analysis to derive a simpler
reduced bulk model that already incorporates the electrochemical properties of
the double layers into a set of new boundary conditions. With the reduced model,
we analyze the double layer capacitance for a metal-electrolyte interface.
PMID- 26415593
TI - Taurine Protected Against the Impairments of Neural Stem Cell Differentiated
Neurons Induced by Oxygen-Glucose Deprivation.
AB - Cell transplantation of neural stem cells (NSCs) is a promising approach for
neurological recovery both structurally and functionally. However, one big
obstacle is to promote differentiation of NSCs into neurons and the followed
maturation. In the present study, we aimed to investigate the protective effect
of taurine on the differentiation of NSCs and subsequent maturation of their
neuronal lineage, when exposed to oxygen-glucose deprivation (OGD). The results
suggested that taurine (5-20 mM) promoted the viability and proliferation of
NSCs, and it protected against 8 h of OGD induced impairments. Furthermore, 20 mM
taurine promoted NSCs to differentiate into neurons after 7 days of culture, and
it also protected against the suppressive impairments of 8 h of OGD.
Consistently, taurine (20 mM) promoted the neurite sprouting and outgrowth of the
NSC differentiated neurons after 14 days of differentiation, which were
significantly inhibited by OGD (8 h). At D21, the mushroom spines and spine
density were promoted or restored by 20 mM taurine. Taken together, the enhanced
viability and proliferation of NSCs, more differentiated neurons and the promoted
maturation of neurons by 20 mM taurine support its therapeutic application during
stem cell therapy to enhance neurological recovery. Moreover, it protected
against the impairments induced by OGD, which may highlight its role for a more
direct therapeutic application especially in an ischemic stroke environment.
PMID- 26415595
TI - pi-Extension of a 4-ethoxy-1,3-thiazole via aryl alkyne cross coupling: synthesis
and exploration of the electronic structure.
AB - A series of four donor aryl alkynyl substituted thiazole derivatives 3a-d and
three similar aryl donor-acceptor systems 6a-c have been synthesized. All
compounds bear different electron-donating groups in the 5-position of the
thiazole core. The influence of both electron donor strength and the additional
phenylethynyl unit on photophysical properties, i.e. UV/Vis absorption,
fluorescence emission and fluorescence lifetime, has been evaluated.
Additionally, theoretical calculations have been performed at the CAM-B3LYP/6
31+G(d,p) level and good agreement with the experimental data has been achieved.
The new derivatives synthesized via palladium catalyzed cross coupling are
characterised by moderately strong emission between 474 and 538 nm (PhiF = 0.35
0.39) and Stokes' shifts ranging from 0.54 to 0.79 eV (4392-6351 cm(-1)). The
smaller chromophores of type 6 exhibit modest to high fluorescence emission (PhiF
= 0.45-0.76) between 470 and 529 nm and their Stokes' shifts range from 0.59 to
0.65 eV (4765-5251 cm(-1)).
PMID- 26415594
TI - Effects on Spatial Cognition and Nociceptive Behavior Following Peripheral Nerve
Injury in Rats with Lesion of the Striatal Marginal Division Induced by Kainic
Acid.
AB - Neuropathic pain and cognitive deficit are frequently comorbidity in clinical,
but their underlying correlation and mechanisms remain unclear. Here, we utilized
a combined rat model including kainic acid (KA) injection into bilateral striatal
marginal division and chronic constriction nerve injury (CCI). PET/CT scans
revealed that the SUVmax of KA rats was significantly decreased when compared to
naive and saline rats. In contrast to the naive and saline rats, KA rats had
longer latencies in locating the hidden platform on day 4, 5 in Morris water maze
task. Thermal hyperalgesia and mechanical allodynia of KA rats were alleviated
following CCI. Immunostaining results showed that substance P was markedly
increased within ipsilateral spinal cord dorsal horn of KA rats after CCI,
especially on the post-operative day 14. By means of real-time PCR, the up
regulation of GluR within ipsilateral spinal cord dorsal horn was observed in all
KA and CCI rats. PKCgamma, IL-6 and NF-kappaB were up-regulated in both CCI rats
when compared to naive and their respective sham rats. These results suggest that
cognitive impairment of rats altered the pain behaviors, and these intracellular
regulators play crucial roles in the process of neuropathic pain.
PMID- 26415598
TI - Aggression Norms in the Classroom Social Network: Contexts of Aggressive Behavior
and Social Preference in Middle Childhood.
AB - In a cross-sectional sample of African-American 2nd-4th grade students (N = 681),
we examine the moderating effects of classroom overt and relational aggression
norms on peers' social acceptance of classmates who exhibit overt and relational
aggression in urban schools. Extending theory and research on classroom norms, we
integrate social network data to adjust aggression norms based on children's
direct and indirect connections in the classroom. Results of multilevel models
indicate that network-based classroom aggression norms moderated relations
between children's aggressive behavior and their social preference. Specifically,
children benefited socially when their form of aggressive behavior fit with what
was normative in the classroom social context. The moderating effect of classroom
aggression norms was stronger for the association between overt aggression and
social preference than relational aggression and social preference. Relationally
aggressive youth were socially preferred by peers regardless of the classroom
norm, although this positive association was magnified in classrooms with higher
levels of relational aggression. Future research focused on aggression norms
within classroom social networks are discussed and implications for school
prevention efforts are considered.
PMID- 26415596
TI - The association of cholesterol absorption gene Numb polymorphism with Coronary
Artery Disease among Han Chinese and Uighur Chinese in Xinjiang, China.
AB - BACKGROUND: Hypercholesterolemia is a major risk factor for coronary artery
disease (CAD). As Numb is an important regulating factor for intestinal
cholesterol absorption and plasma cholesterol level, the aim of the present study
is to assess the association between human Numb gene polymorphism and CAD among
Han and Uighur Chinese. METHODS: We have conducted two independent case-control
studies in Han Chinese (384 CAD patients and 433 controls) and Uighur Chinese
(506 CAD patients and 351 controls) subjects. All subjects were genotyped for
four kinds of SNPs (rs12435797, rs2108552, rs1019075 and rs17781919) and SNP is
used as a genetic marker for human Numb gene. Genotyping was undertaken using
TaqMan SNP genotyping assay, and the subjects' ethnicity and gender were
considered in the analysis. RESULTS: We found that rs2108552 was associated with
CAD in the dominant model (CC vs CG + GG) for the total Han Chinese population (n
= 200) and Han Chinese males (n = 115) (P = 0.004 and P = 0.001, respectively).
The difference remained statistically significant after multivariate adjustment
(total: OR = 1.687, P = 0.004; male: OR = 1.498, P = 0.006). Further, for the
total (n = 817) and male (n = 490) Han Chinese, the frequency of the haplotype (T
C-T-C) was significantly higher in the CAD patients than in the controls (P =
0.004 and P = 0.002), and the frequency of the haplotype (G-G-T-C) was
significantly lower in the CAD patients than in the control subjects (P = 0.013,
P = 0.007). In addition, for the total (n = 857) and male (n = 582) Uighur
Chinese, we observed that rs12435797 was associated with CAD in an additive and
recessive model (P = 0.021 and P = 0.009; P = 0.048 and P = 0.034). However, the
difference did not remain statistically significant after multivariate
adjustment. The overall distribution of rs2108552, rs1019075 and rs17781919
genotypes, alleles and the frequency of the haplotype established by four SNPs
showed no significant difference between CAD patients and control subjects in the
total, male and female Uighur Chinese. CONCLUSIONS: The results of this study
indicate that CC genotype of rs2108552 and T-C-T-C haplotypes in Numb gene is a
possible risk genetic marker and G allele and G-G-T-C haplotypes is a possible
protective genetic marker for CAD in male Han Chinese.
PMID- 26415597
TI - Maternal psychological distress in primary care and association with child
behavioural outcomes at age three.
AB - Observational studies indicate children whose mothers have poor mental health are
at increased risk of socio-emotional behavioural difficulties, but it is unknown
whether these outcomes vary by the mothers' mental health recognition and
treatment status. To examine this question, we analysed linked longitudinal
primary care and research data from 1078 women enrolled in the Born in Bradford
cohort. A latent class analysis of treatment status and self-reported distress
broadly categorised women as (a) not having a common mental disorder (CMD) that
persisted through pregnancy and the first 2 years after delivery (N = 756, 70.1
%), (b) treated for CMD (N = 67, 6.2 %), or (c) untreated (N = 255, 23.7 %).
Compared to children of mothers without CMD, 3-year-old children with mothers
classified as having untreated CMD had higher standardised factor scores on the
Strengths and Difficulties Questionnaire (d = 0.32), as did children with mothers
classified as having treated CMD (d = 0.27). Results were only slightly
attenuated in adjusted analyses. Children of mothers with CMD may be at risk for
socio-emotional and behavioural difficulties. The development of effective
treatments for CMD needs to be balanced by greater attempts to identify and treat
women.
PMID- 26415599
TI - PROKARYO: an illustrative and interactive computational model of the lactose
operon in the bacterium Escherichia coli.
AB - BACKGROUND: We are creating software for agent-based simulation and visualization
of bio-molecular processes in bacterial and eukaryotic cells. As a first example,
we have built a 3-dimensional, interactive computer model of an Escherichia coli
bacterium and its associated biomolecular processes. Our illustrative model
focuses on the gene regulatory processes that control the expression of genes
involved in the lactose operon. Prokaryo, our agent-based cell simulator,
incorporates cellular structures, such as plasma membranes and cytoplasm, as well
as elements of the molecular machinery, including RNA polymerase, messenger RNA,
lactose permease, and ribosomes. RESULTS: The dynamics of cellular 'agents' are
defined by their rules of interaction, implemented as finite state machines. The
agents are embedded within a 3-dimensional virtual environment with simulated
physical and electrochemical properties. The hybrid model is driven by a
combination of (1) mathematical equations (DEQs) to capture higher-scale
phenomena and (2) agent-based rules to implement localized interactions among a
small number of molecular elements. Consequently, our model is able to capture
phenomena across multiple spatial scales, from changing concentration gradients
to one-on-one molecular interactions. We use the classic gene regulatory
mechanism of the lactose operon to demonstrate our model's resolution, visual
presentation, and real-time interactivity. Our agent-based model expands on a
sophisticated mathematical E. coli metabolism model, through which we highlight
our model's scientific validity. CONCLUSION: We believe that through illustration
and interactive exploratory learning a model system like Prokaryo can enhance the
general understanding and perception of biomolecular processes. Our agent-DEQ
hybrid modeling approach can also be of value to conceptualize, illustrate, and-
eventually--validate cell experiments in the wet lab.
PMID- 26415600
TI - Fixed and Modifiable Correlates of Drug-Eluting Stent Thrombosis From a Large All
Comers Registry: Insights From ADAPT-DES.
AB - BACKGROUND: Previous studies evaluating correlates of stent thrombosis (ST) have
included mostly patients with bare metal stents and early-generation drug-eluting
stents (DES) and have not systematically evaluated the role of intravascular
ultrasound-guided stenting and high platelet reactivity on clopidogrel. The
purpose of this study was to evaluate the frequency and correlates of ST in
patients receiving DES, specifically examining the impact of risk factors
modifiable by physician and patient behavior. METHODS AND RESULTS: Assessment of
Dual Anti-platelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a
multicenter, prospective study in patients undergoing successful coronary
intervention with DES in whom routine platelet reactivity testing was performed.
Definite or probable ST occurred in 92 (1.1%) of 8582 patients within 2 years.
Independent baseline correlates of ST included presentation with an acute
coronary syndrome (hazard ratio [HR]=1.81, P=0.01), insulin-treated diabetes
mellitus (HR=1.91, P=0.02), previous myocardial infarction (HR=1.75, P=0.02), and
peripheral arterial disease (HR=2.01, P=0.01). Independent treatment-related
correlates included use of early generation DES (HR=1.75, P=0.02), no procedural
intravascular ultrasound guidance (HR=1.75, P=0.04), and premature
discontinuation of dual antiplatelet therapy (HR=2.67, P=0.003); high platelet
reactivity on clopidogrel trended as a correlate of ST (HR=1.49, P=0.08). The 2
year risk of ST ranged from 0.3% to 10.0% when 0 to 3 modifiable risk factors
were present. CONCLUSIONS: After successful DES implantation, ST occurred within
2 years in 1.1% of patients and was strongly associated with fixed and modifiable
risk factors. The frequency of ST may be reduced with intravascular ultrasound
guided stenting, assiduous adherence to dual antiplatelet therapy, and adequate
P2Y12 platelet receptor inhibition. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00638794.
PMID- 26415601
TI - Letter by Nunez-Gil et al Regarding Article, "Is Aspiration Thrombectomy
Beneficial in Patients Undergoing Primary Percutaneous Coronary Intervention?
Meta-Analysis of Randomized Trials".
PMID- 26415602
TI - Response to Letter Regarding Article, "Is Aspiration Thrombectomy Beneficial in
Patients Undergoing Primary Percutaneous Coronary Intervention? Meta-Analysis of
Randomized Trials".
PMID- 26415603
TI - Global change feed-back inhibits cyanobacterial photosynthesis.
AB - Cyanobacteria are an important component of aquatic ecosystems, with a
proliferation of massive cyanobacterial blooms predicted worldwide under
increasing warming conditions. In addition to temperature, other global change
related variables, such as water column stratification, increases in dissolved
organic matter (DOM) discharge into freshwater systems and greater wind stress
(i.e., more opaque and mixed upper water column/epilimnion) might also affect the
responses of cyanobacteria. However, the combined effects of these variables on
cyanobacterial photosynthesis remain virtually unknown. Here we present evidence
that this combination of global-change conditions results in a feed-back
mechanism by which, fluctuations in solar ultraviolet radiation (UVR, 280-400 nm)
due to vertical mixing within the epilimnion act synergistically with increased
DOM to impair cyanobacterial photosynthesis as the water column progressively
darkens. The main consequence of such a feed-back response is that these
organisms will not develop large blooms in areas of latitudes higher than 30
degrees , in both the Northern and Southern Hemispheres, where DOM inputs and
surface wind stress are increasing.
PMID- 26415604
TI - Hyperparathyroidism Associated with Long-Term Proton Pump Inhibitors Independent
of Concurrent Bisphosphonate Therapy in Elderly Adults.
AB - OBJECTIVES: To measure the effect of proton pump inhibitors (PPIs), with and
without concurrent bisphosphonates, on parathyroid hormone (PTH), vitamin D, and
calcium. DESIGN: Retrospective chart review of individuals 60 years and older.
Subjects with reduced renal function (creatinine >1.3 mg/dL) and low vitamin D
(<30 ng/mL) were excluded. SETTING: Academic geriatric outpatient center in
southern midwest. PARTICIPANTS: Individuals aged 60 and older with concurrent
calcium, PTH, vitamin D, and creatinine laboratory measurements (N = 80) meeting
labeled criteria. MEASUREMENTS: Serum calcium, PTH, vitamin D, and creatinine.
RESULTS: Chronic PPI exposure was associated with statistically significantly
higher PTH (65.5 vs 30.3 pg/mL, P < .001; normal range 10-55 pg/mL) and lower
calcium (9.1 vs 9.4 mg/dL, P = .02; normal range 8.5-10.5 mg/dL) than no PPI
exposure. Chronic PPI exposure with concurrent BP therapy was associated with
statistically significantly higher PTH (65.2 vs 43.4 pg/mL, P = .05) and lower
calcium (9.2 vs 9.6 mg/dL, P = .04) than BP therapy only. CONCLUSION: Based on
the present study, chronic PPI exposure in elderly adults is associated with mild
hyperparathyroidism regardless of concurrent oral BP administration.
PMID- 26415605
TI - Analytical performance of a point-of-care device in monitoring patients on oral
anticoagulation with vitamin K antagonists.
AB - BACKGROUND: [Please check the following sentence for clarity: "Point-of-care
devices measuring international normalized ratio have clinical appeal, reports of
'off-label' in-hospital/primary care use report improved time to
intervention/dose adjustment."]Point-of-care devices measuring international
normalized ratio have clinical appeal, reports of 'off-label' in-hospital/primary
care use report improved time to intervention/dose adjustment. We evaluated the
accuracy and precision of a device for such multiple patient use compared to a
reference laboratory. METHODS: The point-of-care international normalized ratio
result of patients on oral anticoagulation at the Vascular Surgery clinic was
compared to the reference to check for statistical and clinical correlation. This
was a prospective case-control study design with sample size calculated for
sensitivity of 87.5%, precision 5% and desired confidence level 95%. RESULTS:
There were 168 patients tested; 55% were male, the mean age was 45.4. Sixty per
cent were in the target international normalized ratio range. Tests were done for
statistical and clinical correlation. The international normalized ratio range
using the point-of-care device was 0.8-7.5 (reference lab 0.8-10), mean
international normalized ratio was 2.22 +/- 1.6 (point-of-care device) compared
to 2.46 +/- 1.3 (reference lab). The mean absolute difference was 0.79 +/- 0.92
and the mean relative difference was 8.1% +/- 1.03. Data was analysed using a
Bland-Altman plot yielding a mean of 0.738 (standard deviation 0.92). Concordance
between the tests was 75% with r2 = 0.52 on linear regression. Using an error
grid plot, excellent clinical correlation was seen in 63.8%. In 5.4% major
corrective action was needed but potentially missed if relying on the point-of
care device. CONCLUSION: The accuracy and precision of this point-of-care device
is moderate. It may have potential utility only where access to a reference lab
is difficult.
PMID- 26415606
TI - [Radiation-free diagnosis of scoliosis : An overview of the surface and spine
topography].
AB - BACKGROUND: Scoliosis is a complex three-dimensional deformity of the spine,
which usually occurs during childhood and adolescence. Up to now, whole spine X
rays have been the therapeutic gold standard in the diagnosis and follow-up of
scoliosis. AIM: This review gives a brief overview of the history, technical
background and possible fields of use for video-rasterstereography METHODS:
Alternative measurement systems have been developed over the past few years for
the treatment of scoliosis, because of the risk of radiation exposure of X-rays.
The rasterstereographic system Formetric (Diers International GmbH, Schlagenbad)
allows a radiation-free, three-dimensional analysis of the back surface and the
spine. OUTLOOK: Even dynamic measurements can now be conducted with this
rasterstereographic system, which will help to further understand and analyze the
human spine.
PMID- 26415607
TI - [Physical therapy for idiopathic scoliosis].
AB - OBJECTIVE: The objective is the description and summary of the current state of
idiopathic scoliosis treatment with physical therapy based on new scientific
knowledge and concluded from more than 15 years of experience as a leading
physician in two well-known clinics specializing in the conservative treatment of
scoliosis. MATERIALS AND METHODS: Based on current scientific publications on
physical therapy in scoliosis treatment and resulting from the considerable
personal experience gained working with conservative treatment and consulting
scoliosis patients (as inpatients and outpatients), the current methods of
physical therapy have been compared and evaluated. RESULTS: Physical therapy
according to Schroth and Vojta therapy are at present the most common and
effective methods in the physical treatment of idiopathic scoliosis. These
methods can be applied during inpatient or outpatient treatment or intensified in
the practice of specialized therapists. DISCUSSION: As there are only a few
scientific studies on this subject, the author's findings are based mainly on his
own experiences of the conservative treatment of idiopathic scoliosis. Athough
these experiences are the results of over 15 years of working in the field of
therapy, and the Schroth method in combination with corrective bracing presents
highly promising results, it would nevertheless be desirable to conduct detailed
scientific studies to verify the effectiveness of conservative treatment.
PMID- 26415609
TI - Isolation of Circulating Melanoma Cells.
AB - Circulating melanoma cells (CMCs) represent critical mediators of metastatic
melanoma progression. However, isolation and characterization of CMCs has been
challenging due to the low frequency of these cells and the paucity of melanoma
specific cell surface markers. Herein, we describe a method for the isolation of
CMCs that employs two independent markers, displays high sensitivity for CMC
enrichment, and can be readily adapted to include additional molecular melanoma
markers of interest. CMCs isolated by this method are enriched for ABCB5-positive
melanoma stem cells, are tumorigenic in xenotransplantation assays, and can be
used for phenotypical, genetic, and functional investigations of CMC biology.
PMID- 26415608
TI - [Simultaneous thoracoscopically assisted anterior release in prone position and
posterior scoliosis correction : What are the limits?].
AB - BACKGROUND: In spite of modern pedicle-based systems, the correction of a rigid
rib hump or hypokyphosis remains a problem in posterior-only scoliosis surgery.
As there has so far been no reliable method of predicting the intraoperative
extent of kyphosis restoration or rib hump correction by posterior-only surgery,
it has been difficult to determine the indication for an additional anterior
release. METHODS: The method described here circumvents this dilemma. Like an
optional module, horacoscopically assisted release in prone position (TARP) can
be added when it is obvious during posterior surgery that the correction is
insufficient. RESULTS: Between 1996 and 2005, a total of 161 patients (115 male,
46 female) under the age of 30, including 113 cases of idiopathic scoliosis, were
released by simultaneous TARP and posterior surgery. Using the two-portal
technique, 131 were mobilized from the right and 30 from the left hand side.
Average surgical time spanned 69 min, in which on average 3.2 apical segments
were addressed. In 3 individuals, an additional retroperitoneoscopic release was
used to liberate a rigid lumbar curve. After 10 years, in a prospectively
evaluated subgroup of 32 patients with adolescent idiopathic scoliosis, the index
curve had maintained a coronal correction of 70 % (immediately post-surgery 75
%), kyphosis was permanently normalized at 30 degrees (Th5-Th12), and indirect
rib hump was reduced to 2.2 cm. In 23 out of 32 patients the lumbar curve
corrected spontaneously, obviating the need for fusion. In 13 patients, the lower
instrumented vertebra lay at Th12 or higher, thus leaving the thoraco-lumbar
junction fairly free. Minor complications (Huang 1or 2) occurred in 4 patients; 1
patient with hematothorax required revision. A distance <25 mm from the spine to
the chest wall precludes TARP. Other limitations (e.g., pleural adhesions) were
not encountered. CONCLUSION: Long-term evaluation after 10-18 years shows that an
additional thoracoscopically assisted anterior release at the same time as a
posterior standard scoliosis procedure is a justified and effective tool,
yielding better results and maintaining them.
PMID- 26415610
TI - Pre-operative serum alkaline phosphatase as a predictive indicator of post
operative hypocalcaemia in patients undergoing total thyroidectomy.
AB - OBJECTIVE: This study aimed to evaluate whether a pre-operative elevated serum
alkaline phosphatase level is a potential predictor of post-operative
hypocalcaemia after total thyroidectomy. METHODS: Data was retrospectively
collected from the case notes of patients who had undergone total thyroidectomy.
Patients were divided into Graves' disease and non-Graves' groups. Pre-operative
and post-operative biochemical markers, including serum calcium, alkaline
phosphatase and parathyroid hormone levels, were reviewed. RESULTS: A total of
225 patients met the inclusion criteria. Graves' disease was the most common
indication (n = 134; 59.5 per cent) for thyroidectomy. Post-operative
hypocalcaemia developed in 48 patients (21.3 per cent) and raised pre-operative
serum alkaline phosphatase was noted in 94 patients (41.8 per cent). Raised pre
operative serum alkaline phosphatase was significantly associated with post
operative hypocalcaemia, particularly in Graves' disease patients (p < 0.05).
CONCLUSION: Pre-operative serum alkaline phosphatase measurements help to predict
post-thyroidectomy hypocalcaemia, especially in patients who do not develop
hypoparathyroidism. Ascertaining the pre-operative serum alkaline phosphatase
level in patients undergoing total thyroidectomy may help surgeons to identify at
risk patients.
PMID- 26415611
TI - Erratum to: Plasma levels of matrix metalloproteinase-2, -3, -10, and tissue
inhibitor of metalloproteinase-1 are associated with vascular complications in
patients with type 1 diabetes: the EURODIAB Prospective Complications Study.
PMID- 26415612
TI - The Effectiveness of Visual Short-Time Neurofeedback on Brain Activity and
Clinical Characteristics in Alcohol Use Disorders: Practical Issues and Results.
AB - The present study was carried out to examine the efficacy of alpha/theta
neurofeedback (NF) with a new visual paradigm in a cohort of alcohol use
disordered (AUD) patients (n = 25) treated in an Austrian therapeutic community
center. The experimental study design focused on changes in absolute and relative
resting EEG band power as well as in clinical variables, including depression
(Beck Depresion Inventory [BDI-V]), psychiatric symptoms (Brief Symptom Inventory
[BSI], coping (Freiburg Questionnaire on Coping with Illness [FKV-lis]),
psychotherapy motivation (Therapy Motivation Questionnaire [FPTM-23]), sense of
coherence (Sense of Coherence Scale [SOC-13]), posttraumatic growth
(Posttraumatic Growth Inventory [PPR]), and alcohol cravings (Alcohol Craving
Questionnaire [ACQ]). For measuring training effects, participants were randomly
allocated to 2 groups: an experimental group (EG, n = 13) and a control group
(CG, n = 12). Patients in EG received 12 sessions of visual NF training over a
period of 6 weeks to enhance alpha (8-12 Hz) and theta (4-7 Hz) frequency band
power in addition to the standard treatment program of the rehabilitation center.
Participants in CG received no additional NF intervention. The multivariate
analysis of covariance (MANCOVA) showed a change by trend in absolute alpha and
theta power in the EG. Even though no MANCOVA effects were found in the clinical
scales, AUD patients reported increasing control of their brain activity during
the course of NF. However, changes in several clinical scales (BDI-V, BSI, FKV
lis, PPR) from pre- to posttest were observed only in the EG contrary to the CG.
The findings of this pilot study provide first evidence for the practicality and
effectiveness of visual short-term NF as an additive intervention in the
therapeutic community.
PMID- 26415613
TI - Robot-sewn Ivor-Lewis anastomosis: preliminary experience and technical details.
AB - INTRODUCTION: Robot-assisted minimally invasive esophagectomy with intra-thoracic
anastomosis showed encouraging results but there is a lack of data to demonstrate
the safety and feasibility. OBJECTIVE: The aim of this study is to report our
experience in RA-ILE (robotic-assisted Ivor-Lewis esophagectomy) with robotic
hand-sewn anastomosis. METHODS: This is a retrospective study of patients who
underwent robotic-assisted esophagectomy in prone position with intrathoracic
anastomosis for malignant neoplasm of the esophagus or esophago-gastric junction.
RESULTS: From January 2012 to December 2014 we performed eight completely robot
assisted esophagectomy without intra-operative complication. The mortality rate
at 30-day was zero. In two patients we observed a partial leakage of the gastric
tube that required revision. The mean operative time was 499 +/- 46 min including
robotic set up and patient positioning. The median hospital-stay was 10 days.
Complete (R0) resection was accomplished in all patients and the mean number of
lymph nodes removed was 37.6 +/- 14 .7. CONCLUSIONS: This preliminary experience
suggests that robotic-assisted RA-ILE for malignant lesions is a real surgical
option compared with conventional surgery with satisfactory results. Copyright
(c) 2015 John Wiley & Sons, Ltd.
PMID- 26415614
TI - Evolving understanding on the aetiology of thermally provoked itch.
AB - BACKGROUND AND OBJECTIVES: Itch is one of the major symptoms in dermatology
clinics, and severely impairs the quality of life. Itch is frequently produced by
environmental stimuli, especially heat or warmth. Changes of temperature on the
skin surface and noxious heat stimuli augment and develop itch, respectively.
Thermally provoked itch is sometimes intractable with existing treatments. DATA
BASES AND DATA TREATMENT: Recent researches, linking heat sensation and itch,
were searched in MEDLINE literature database through PubMed. RESULTS: Recent
studies of the transient receptor potential cation channel subfamily vanilloid
type 1 (TRPV1), the calcitonin gene-related peptide (CGRP) and the vesicular
glutamate transporter 2 (VGLUT2), which link noxious heat and itch, contribute to
a much better understanding of the thermally evoked itch process. From a clinical
perspective, a warm sensation is a major provocative factor for subjects with
atopic dermatitis. The accumulation of artemin (also known as enovin or
neublastin) in the dermis of lesional skin can possibly provide a pathological
mechanism for warmth-provoked itch. CONCLUSIONS: This mini-review describes
recent results of both basic and clinical research related to thermally provoked
itch.
PMID- 26415615
TI - Recommendations for managing a suboptimal response to biologics for moderate-to
severe psoriasis: A Belgian perspective.
AB - Over the past decade, biologics have become the gold standard in the treatment of
moderate-to-severe psoriasis for patients who have failed or who have
contraindications to traditional systemic treatments. However, although practical
recommendations on how to treat a suboptimal response to biologics exist in other
chronic inflammatory diseases, they are only just beginning to emerge for
psoriasis. This article aims to formulate recommendations in the case of a
suboptimal response of psoriasis to biologics in the Belgian setting. A Belgian
taskforce of psoriasis experts was convened to review the results of a literature
search and formulate recommendations based on the available evidence and provide
expert opinion to address gaps in the evidence. The taskforce has proposed a
treatment algorithm for patients with a primary non-response or a secondary loss
of response to help address an unmet need. Expert recommendations have been
developed to address treatment strategies in case of a primary or secondary
suboptimal response to biologics in the treatment of moderate-to-severe psoriasis
in Belgium.
PMID- 26415617
TI - Effects of the ornidazole enantiomers on the central nervous system: Involvement
of the GABAA receptor.
AB - This is the preliminary study of the sedative and muscle relaxation activity of
ornidazole enantiomers, which are widely used in the treatment of susceptible
protozoal infections and anaerobic bacterial infections. Adverse effects on the
central nervous system (CNS) are the main side effects of ornidazole during its
clinical application. The aim of this study was to compare the different central
inhibitory effects between S-(-) ornidazole and R-(+) ornidazole in mice and
clarify the possible mechanisms. In the present study, central effects of
ornidazole were evaluated by open-field test and rota-rod test, and such effects
were reversed by pre-treatment with flumazenil (i.p., 10 mg/kg) suggesting that
ornidazole exhibits such action by interacting with the GABAergic system. Then,
the functional difference between S-(-) ornidazole and R-(+) ornidazole was
further explored by evaluating the contents of glutamate (Glu) and gamma
aminobutyric acid (GABA) in the brain, and Western blot was used to measure
glutamic acid decarboxylase (GAD65/67) expression in the mice cerebral cortex. We
found that R-(+) ornidazole mediated an increase in GABA level while decreased
the level of glutamate through upregulation of GAD65/67 in the cerebral cortex.
Taken together, our study suggests that R-(+) ornidazole mediate stronger central
inhibitory effects than S-(-) ornidazole through interaction with the GABAergic
system.
PMID- 26415618
TI - In vitro anticancer activity of methyl caffeate isolated from Solanum torvum
Swartz. fruit.
AB - The present study was undertaken to investigate the anticancer activity of methyl
caffeate isolated from Solanum torvum Swartz. fruit and to explore the molecular
mechanisms of action in MCF-7 cells. Cytotoxic properties of hexane, ethyl
acetate and methanol extracts were carried out against MCF-7 cells using the 3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Ethyl acetate
extract showed good cytototoxic activities compared to hexane and methanol
extracts. Methyl caffeate was isolated from the ethyl acetate extract using
column chromatography. Cytotoxic properties of methyl caffeate was investigated
against MCF-7, A549, COLO320, HepG-2 and Vero cells. The compound showed potent
cytotoxic properties against MCF-7 cells compared to A549, COLO320 and HepG-2
cells. Methyl caffeate significantly reduced cell proliferation and increased
formation of fragmented DNA and apoptotic body in MCF-7 cells. Bcl-2, Bax, Bid,
p53, caspase-3, PARP and cytochrome c release were detected by western blot
analysis. The activities of caspases-3 and PARP gradually increased after the
addition of isolated compound. Bcl-2 protein was down regulated; Bid and Bax were
up regulated after the treatment with methyl caffeate. Molecular docking studies
showed that the compound bound stably to the active sites of poly (ADP-ribose)
polymerase-1 (PARP1), B cell CLL/lymphoma-2 (BCL-2), E3 ubiquitin-protein ligase
(MDM2) and tubulin. The results strongly suggested that methyl caffeate induced
apoptosis in MCF-7 cells via caspase activation through cytochrome c release from
mitochondria.
PMID- 26415616
TI - A global meta-analysis of the relative extent of intraspecific trait variation in
plant communities.
AB - Recent studies have shown that accounting for intraspecific trait variation (ITV)
may better address major questions in community ecology. However, a general
picture of the relative extent of ITV compared to interspecific trait variation
in plant communities is still missing. Here, we conducted a meta-analysis of the
relative extent of ITV within and among plant communities worldwide, using a data
set encompassing 629 communities (plots) and 36 functional traits. Overall, ITV
accounted for 25% of the total trait variation within communities and 32% of the
total trait variation among communities on average. The relative extent of ITV
tended to be greater for whole-plant (e.g. plant height) vs. organ-level traits
and for leaf chemical (e.g. leaf N and P concentration) vs. leaf morphological
(e.g. leaf area and thickness) traits. The relative amount of ITV decreased with
increasing species richness and spatial extent, but did not vary with plant
growth form or climate. These results highlight global patterns in the relative
importance of ITV in plant communities, providing practical guidelines for when
researchers should include ITV in trait-based community and ecosystem studies.
PMID- 26415619
TI - O-Alkylated derivatives of quercetin induce apoptosis of MCF-7 cells via a
caspase-independent mitochondrial pathway.
AB - The aim of this study was to investigate the antitumor effects of two novel
alkylated derivatives of quercetin, 7-O-butylquercetin (BQ) and 7-O
geranylquercetin (GQ), in MCF-7 human breast cancer cells and explore the
possible cellular mechanism of the related apoptotic effects. Our data showed
that BQ and GQ were more toxic to MCF-7 cells and had better accumulation ability
in MCF-7 cells than quercetin. Morphological observations and DNA fragmentation
pattern suggested that the derivatives could induce apoptosis in MCF-7 cells.
Derivatives-induced apoptosis could not be reversed by Z-VAD-FMK and N-acetyl
cysteine demonstrated that the apoptosis was independent on caspase and reactive
oxygen species. Western blot assay showed that endonuclease G and apoptosis
inducing factor might be relative to the apoptosis. Alkylation of quercetin at 7
O position can enhance the apoptosis inducing effect and cell accumulation
ability relative to quercetin. This structural alteration brings changes on
apoptosis pathway as well.
PMID- 26415620
TI - Pharmacokinetics and immunogenicity of a recombinant human butyrylcholinesterase
bioscavenger in macaques following intravenous and pulmonary delivery.
AB - Recombinant (r) and native butyrylcholinesterse (BChE) are potent bioscavengers
of organophosphates (OPs) such as nerve agents and pesticides and are undergoing
development as antidotal treatments for OP-induced toxicity. Because of the
lethal properties of such agents, regulatory approval will require extensive
testing under the Animal Rule. However, human (Hu) glycoprotein biologicals, such
as BChE, present a challenge for assessing immunogenicity and efficacy in
heterologous animal models since any immune responses to the small species
differences in amino acids or glycans between the host and biologic may alter
pharmacodynamics and preclude accurate efficacy testing; possibly underestimating
their potential protective value in humans. To establish accurate pharmacokinetic
and efficacy data, an homologous animal model has been developed in which native
and PEGylated forms of CHO-derived rMaBChE were multiply injected into homologous
macaques with no induction of antibody. These now serve as controls for assessing
the pharmacokinetics and immunogenicity in macaques of multiple administrations
of PEGylated and unmodified human rBChE (rHuBChE) by both intravenous (IV) and
pulmonary routes. The results indicate that, except for maximal concentration
(Cmax), the pharmacokinetic parameters following IV injection with heterologous
PEG-rHuBChE were greatly reduced even after the first injection compared with
homologous PEG-rMaBChE. Anti-HuBChE antibody responses were induced in all
monkeys after the second and third administrations regardless of the route of
delivery; impacting rates of clearance and usually resulting in reduced
endogenous MaBChE activity. These data highlight the difficulties inherent in
assessing pharmacokinetics and immunogenicity in animal models, but bode well for
the efficacy and safety of rHuBChE pretreatments in homologous humans.
PMID- 26415623
TI - Entropy-stabilized oxides.
AB - Configurational disorder can be compositionally engineered into mixed oxide by
populating a single sublattice with many distinct cations. The formulations
promote novel and entropy-stabilized forms of crystalline matter where metal
cations are incorporated in new ways. Here, through rigorous experiments, a
simple thermodynamic model, and a five-component oxide formulation, we
demonstrate beyond reasonable doubt that entropy predominates the thermodynamic
landscape, and drives a reversible solid-state transformation between a
multiphase and single-phase state. In the latter, cation distributions are proven
to be random and homogeneous. The findings validate the hypothesis that
deliberate configurational disorder provides an orthogonal strategy to imagine
and discover new phases of crystalline matter and untapped opportunities for
property engineering.
PMID- 26415622
TI - Prevalence of Alcohol and Other Substance Use in Patients with Eating Disorders.
AB - OBJECTIVE: The major aim of this study was to investigate any association between
binge eating and purging and alcohol and substance use. METHOD: The Eating
Disorder Questionnaire was completed by 2966 patients. Each patient was assigned
to an approximate diagnostic group based on a DSM-5-based algorithm. RESULTS:
Patients with bulimia nervosa (BN) used alcohol/other substances with higher
frequencies compared to patients with anorexia nervosa-restricting type (AN-R),
binge eating disorder (BED), and eating disorder not otherwise specified (EDNOS;
p < 0.001). Patients with anorexia nervosa-binge eating/purging type (AN-BP) were
more likely to use alcohol/substances than those with AN-R [odds ratio for
alcohol use: 3.58 (p < 0.01); odds ratio for substance use: 30.14 (p < 0.01)].
Higher frequencies of binge eating and purging were associated with higher
frequencies of substance use. DISCUSSION: Patients who manifest both binge eating
and purging behaviour are at higher risk of substance use which may have
important treatment implications.
PMID- 26415624
TI - Mediating effects of nocturnal blood pressure and morning surge on the
contributions of arterial stiffness and sodium intake to morning blood pressure:
A path analysis.
AB - BACKGROUND: The aim of this study was to evaluate the mediating effects of
nocturnal blood pressure (BP) and morning surge on the contribution of arterial
stiffness and sodium intake to morning BP in a middle-aged general population.
METHODS: The study included 124 subjects aged 30-59 years, from rural Yeoju
County, Gyeonggi Province, South Korea. Ambulatory BP monitoring, 24 h urinary
sodium excretion (24 h UNa) and brachial-ankle pulse wave velocity (baPWV)
measurements were performed in all subjects. RESULTS: The mean +/- SD age was
48.1 +/- 8.2 years and the proportion of male subjects was 41.1%. After adjusting
for covariates, morning systolic blood pressure (SBP) was significantly
correlated with morning surge [coefficient = 0.761, 95% confidence interval (CI)
0.651-0.872, p < 0.001], nocturnal SBP (coefficient = 0.576, 95% CI 0.454-0.698,
p < 0.001) and baPWV (coefficient = 3.550, 95% CI 1.447-5.653, p = 0.001). Path
analysis modeling revealed that baPWV had significant direct (0.035, p = 0.013)
and indirect effects (0.042, p = 0.012) on morning SBP. The indirect effect
mediated by nocturnal SBP was statistically significant (0.054, p = 0.005), but
the indirect effect mediated by the morning surge was not significant. The 24 h
UNa had no significant direct or indirect effects on morning SBP. CONCLUSION:
baPWV had significant direct and indirect effects on morning SBP. The indirect
effect was mediated by nocturnal SBP, but not by morning surge. The 24 h UNa had
neither significant direct nor indirect effects on morning SBP.
PMID- 26415621
TI - Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic
Lupus Erythematosus.
AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized
by the production of autoantibodies to a broad range of self-antigens. Profiling
the autoantibody repertoire using array-based technology has emerged as a
powerful tool for the identification of biomarkers in SLE and other autoimmune
diseases. Proteomic microarray has the capacity to hold large number of self
antigens on a solid surface and serve as a high-throughput screening method for
the determination of autoantibody specificities. The autoantigen arrays carrying
a wide variety of self-antigens, such as cell nuclear components (nucleic acids
and associated proteins), cytoplasmic proteins, phospholipid proteins, cell
matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific
proteins, have been used for screening of autoantibody specificities associated
with different manifestations of SLE. Arrays containing synthetic peptides and
molecular modified proteins are also being utilized for identification of
autoantibodies targeting to special antigenic epitopes. Different isotypes of
autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes,
can be detected simultaneously with multi-color labeled secondary antibodies.
Serum and plasma are the most common biologic materials for autoantibody
detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and
saliva can also be a source of autoantibody detection. Proteomic microarray as a
multiplexed high-throughput screening platform is playing an increasingly
important role in autoantibody diagnostics. In this article, we highlight the use
of autoantigen microarrays for autoantibody exploration in SLE.
PMID- 26415625
TI - Colorimetric detection of biological hydrogen sulfide using fluorosurfactant
functionalized gold nanorods.
AB - As a well-known environmental pollutant but also an important gaseous
transmitter, the specific detection of hydrogen sulfide (H2S) is significant in
biological systems. In this study, fluorosurfactant functionalized gold nanorods
(FSN-AuNRs) have been proposed to act as selective colorimetric nanoprobes for
H2S. With the combination of strong gold-S interactions and small FSN bilayer
interstices, FSN-AuNRs demonstrate favorable selectivity and sensitivity toward
H2S over other anions and small biological molecules. The practical application
of the present method in biological H2S detection was validated with human and
mouse serum samples. Moreover, the proposed nanoprobe can also be used for
evaluating the activity of H2S synthetase.
PMID- 26415626
TI - Sputum smear-positive pulmonary tuberculosis: Is sputum smear examination
required to discontinue airborne precautions?
AB - OBJECTIVE: Our aim was to evaluate the criteria required to discontinue airborne
precautions for patients presenting with sputum smear-positive pulmonary
tuberculosis as the need for sputum smear examinations is still a matter of
debate. METHOD: We conducted a retrospective study in the University Hospitals of
Strasbourg (France) from July 2011 to July 2013. Our aim was to describe the
results of sputum smear examinations and cultures obtained from treated patients
presenting with drug-sensitive pulmonary tuberculosis. We included 97 patients in
the study. CONCLUSION: Nearly half of patients for whom a sputum smear
examination was performed had a negative sputum direct examination but a positive
culture. According to the literature, those patients are still likely to be
contagious. This questions the safety of discontinuing airborne precautions in
this situation. We also observed a great disparity in physicians' behaviors. Only
half of them waited to get a negative sputum direct examination before
discontinuing airborne precautions.
PMID- 26415627
TI - A Simple Method for the Preparation of TiO2 /Ag-AgCl@Polypyrrole Composite and
Its Enhanced Visible-Light Photocatalytic Activity.
AB - A novel and facile method was developed to prepare a visible-light driven TiO2
/Ag-AgCl@polypyrrole (PPy) photocatalyst with Ag-AgCl nanoparticles supported on
TiO2 nanofibers and covered by a thin PPy shell. During the synthesis, the PPy
shell and Ag-AgCl nanoparticles were prepared simultaneously onto TiO2
nanofibers, which simplified the preparation procedure. In addition, because Ag
AgCl aggregates were fabricated via partly etching the Ag nanoparticles, their
size was well controlled at the nanoscale, which was beneficial for improvement
of the contact surface area. Compared with reference photocatalysts, the TiO2 /Ag
AgCl@PPy composite exhibited an enhanced photodegradation activity towards
rhodamine B under visible-light irradiation. The superior photocatalytic property
originated from synergistic effects between TiO2 nanofibers, Ag-AgCl
nanoparticles and the PPy shell. Furthermore, the TiO2 /Ag-AgCl@PPy composite
could be easily separated and recycled without obvious reduction in activity.
PMID- 26415628
TI - New avenues for improving pancreatic ductal adenocarcinoma (PDAC) treatment:
Selective stroma depletion combined with nano drug delivery.
AB - The effectiveness of chemotherapy in PDAC is hampered by the dynamic interaction
between stroma and cancer cell. The two opposing schools of thought - non
depletion of the stroma vs its depletion - to better drug efficacy are here
discussed. Disrupting stroma-cancer cell interaction to reduce tumor progression
and promote apoptosis is identified as the new direction of treatment for PDAC.
Clinical data have shown that elimination of fibrosis and blockade of the
Hedgehog pathway in stroma effectively promote drug delivery to tumor site and
apoptosis. Reduced stiffness of ECM, lower fibrosis, higher permeability and
higher blood flow after stroma depletion increase drug delivery. Combination
strategies involving selective stroma depletion coupled with chemotherapy is
currently proving to be the most efficient at clinical level. Striking the right
balance between fibrosis depletion and angiogenesis promotion resulting in
enhanced drug delivery and apoptosis is a major challenge. The use of nano drug
delivery devices coupled with stroma depletion is emerging as the next phase
treatment for PDAC. The breakthrough to combat PDAC will likely be a combination
of early diagnosis and the emerging chemotherapy strategies.
PMID- 26415629
TI - Immunolocalization indicates that both original and regenerated lizard tail
tissues contain populations of long retaining cells, putative stem/progenitor
cells.
AB - The regeneration of the tail in lizards is likely sustained by stem/progenitor
cells located in the stump after amputation of the tail. This microscopic and
ultrastructural study shows the localization of 5-bromo-deoxy-uridine (5BrdU)
long retaining labeled cells in different tissues of the tail stump. These
putative stem/progenitor cells are sparsely detected in the epidermis of scales,
adipose tissue, intermuscle connective septa, myosatellite cells, and
perichondrion of the vertebrae. Most of 5BrdU-labeled cells are present in the
bone marrow of vertebrae as hemocytoblasts and reticulate cells, whereas more
numerous myelocytes and polychromatophilic erythroblasts show a variable level of
nuclear labeling. 5BrdU and tritiated-thymidine labeled and unlabeled hemopoietic
cells are seen in circulating vessels and in the blastema where their maturation
is completed. This observation indicates that the entire differentiation span of
both white and red blood cells, at least during tail regeneration, lasts longer
than 4 weeks. Labeled polychromatophilic erythroblasts and heterophilic and
basophilic myelocytes are present in the synusoidal vessels of the regenerating
tail. This study indicates that extravasating blood cells involved in immunity
make large part of the forming blastema cell population, but are replaced by
mesenchymal cells of different origin. The presence of long retaining labeled
cells in tissues of the tail stump is likely connected to the production of
blastema mesenchymal cells. Although no direct cell-lineage study has been done,
histological, immunocytochemical, and autoradiographic studies have indicated
that it is from these tissues that proliferating cells appear mainly localized
after tail amputation and blastema formation.
PMID- 26415630
TI - Tunable release of ophthalmic therapeutics from injectable, resorbable,
thermoresponsive copolymer scaffolds.
AB - The sustained release of ophthalmic therapeutics to the posterior segment of the
eye is a challenge. Injectable polymer materials have the potential to reduce
injection frequency by providing long term therapeutic delivery. Copolymers with
varying N-isopropylacrylamide, acrylamide (AAm), acrylic acid N
hydroxysuccinimide, and (r)-alpha-acryloyloxy-beta,beta-dimethyl-gamma
butyrolactone (DBA) were synthesized by RAFT polymerization to develop
injectable, resorbable, and thermoresponsive copolymer scaffolds. Upon injection
into physiological conditions, these copolymers undergo a temperature induced
gelation to form a drug releasing scaffold. Modification of the copolymer's
AAm/DBA ratio and molecular weight afforded significant and precise control over
the scaffold's physical properties and subsequent drug release profile.
Hydrolytic DBA ring-opening enables redissolution of the copolymers for clearance
from the body. Precise control over the drug release profile from these copolymer
scaffolds by simple alteration of composition and molecular weight provides an
efficient method to customize the minimally invasive delivery of therapeutics to
the posterior segment of the eye. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater
Res Part B: Appl Biomater, 105B: 53-62, 2017.
PMID- 26415631
TI - Exploring the nature of the liquid-liquid transition in silicon: a non-activated
transformation.
AB - In contrast to other glass formers, silicon exhibits a thermodynamic
discontinuity between its liquid and amorphous solid states. Some researchers
have conjectured that a first-order phase transition occurs between two forms of
liquid silicon: the high-density liquid (HDL) and the low-density liquid (LDL).
Despite the fact that several computer simulations have supported a liquid-liquid
phase transition (LLPT) in silicon, recent work based on surface free energy
calculations contradicts its existence and the authors of this work have argued
that the proposed LLPT has been mistakenly interpreted [J. Chem. Phys., 2013,
138, 214504]. A similar controversy has also arisen in the case of water because
of discrepancies in the calculation of its free energy surface [Nature, 2014,
510, 385; J. Chem. Phys., 2013, 138, 214504]. Current evidence supporting or not
supporting the LLPT is mostly derived from the thermodynamic stability of the LDL
phase. Provided that the HDL-LDL transition is a first-order transition, the
formation of LDL silicon should be an activated process. Following this idea, the
nature of the LLPT should be clarified by tracing the kinetic path toward LDL
silicon. In this work, we focus on the transformation process from HDL to LDL
phases and use the mean first passage time (MFPT) method to examine thermodynamic
and dynamic trajectories. The MFPT results show that the presumed HDL-LDL
transition is not characterized by a thermodynamic activated process but by a
continuous dynamic transformation. LDL silicon is actually a mixture of the high
density liquid and a low-density tetrahedral network. We show that the five
membered Si-Si rings in the LDL network play a critical role in stabilizing the
low-density network and suppressing the crystallization.
PMID- 26415632
TI - A finite element model of the L4-L5-S1 human spine segment including the
heterogeneity and anisotropy of the discs.
AB - With the aim to study disc degeneration and the risk of injury during
occupational activities, a new finite element (FE) model of the L4-L5-S1 segment
of the human spine was developed based on the anthropometry of a typical
Colombian worker. Beginning with medical images, the programs CATIA and
SOLIDWORKS were used to generate and assemble the vertebrae and create the soft
structures of the segment. The software ABAQUS was used to run the analyses,
which included a detailed model calibration using the experimental step-wise
reduction data for the L4-L5 component, while the L5-S1 segment was calibrated in
the intact condition. The range of motion curves, the intradiscal pressure and
the lateral bulging under pure moments were considered for the calibration. As
opposed to other FE models that include the L5-S1 disc, the model developed in
this study considered the regional variations and anisotropy of the annulus as
well as a realistic description of the nucleus geometry, which allowed an
improved representation of experimental data during the validation process.
Hence, the model can be used to analyze the stress and strain distributions in
the L4-L5 and L5-S1 discs of workers performing activities such as lifting and
carrying tasks.
PMID- 26415633
TI - Pursuing shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) for
concomitant detection of breast lesions and microcalcifications.
AB - Although tissue staining followed by morphologic identification remains the gold
standard for diagnosis of most cancers, such determinations relying solely on
morphology are often hampered by inter- and intra-observer variability.
Vibrational spectroscopic techniques, in contrast, offer objective markers for
diagnoses and can afford disease detection prior to alterations in cellular and
extracellular architecture by furnishing a rapid "omics"-like view of the
biochemical status of the probed specimen. Here, we report a classification
approach to concomitantly detect microcalcification status and local pathological
state in breast tissue, featuring a combination of vibrational spectroscopy that
focuses on the tumor and its microenvironment, and multivariate data analysis of
spectral markers reflecting molecular expression. We employ the unprecedented
sensitivity and exquisite molecular specificity offered by Au@SiO2 shell-isolated
nanoparticle-enhanced Raman spectroscopy (SHINERS) to probe the presence of
calcified deposits and distinguish between normal breast tissues, fibroadenoma,
atypical ductal hyperplasia, ductal carcinoma in situ (DCIS), and invasive ductal
carcinoma (IDC). By correlating the spectra with the corresponding histologic
assessment, we developed partial least squares-discriminant analysis derived
decision algorithm that provides excellent diagnostic power in the fresh frozen
sections (overall accuracy of 99.4% and 93.6% using SHINs for breast lesions with
and without microcalcifications, respectively). The performance of this decision
algorithm is competitive with or supersedes that of analogous algorithms
employing spontaneous Raman spectroscopy while enabling facile detection due to
the considerably higher intensity of SHINERS. Our results pave the way for rapid
tissue spectral pathology measurements using SHINERS that can offer a novel stain
free route to accurate and economical diagnoses without human interpretation.
PMID- 26415634
TI - Influence of the linkage type between the polymer backbone and side groups on the
surface segregation of methyl groups during film formation.
AB - Although poly(vinyl acetate) (PVAc) differs from poly(methyl acrylate) (PMA) only
in the reversed position of the ester group, a large difference in the
concentration dependence of the casting solution on the corresponding surface
structure of the cast films of PVAc, PMA and poly(methyl methacrylate) (PMMA) was
observed. The hydrophobicity of both PMA and PMMA films increased with increasing
concentration of the corresponding polymer solution, whereas cast PVAc films
showed the reverse trend. The surface structure of the cast films prepared with
different concentrations of the casting solution, characterized by sum frequency
generation (SFG) vibrational spectra, showed that the order of the methylene
groups increased while that of the acetyl methyl group decreased on the surface
of cast PVAc film with increasing concentration of casting solution. However, the
order of the ester methyl group increased and that of methylene groups did not
change for cast PMA films with increasing concentration of casting solution. The
cast PMMA film showed a reverse trend compared with the corresponding PMA film.
It is apparent that well-ordered ester or acetyl methyl groups on the surface,
which are oriented away from the polymer film, rather than methylene groups, play
an important role in determining surface hydrophobicity, as the latter shield the
OC[double bond, length as m-dash]O groups of PVAc, PMA and PMMA film surfaces
from being exposed, resulting in low surface free energy. The reason for this
difference is attributed to the relatively low energy for ester methyl group
reorientation, an ester group structure nearer to the trans state and more
regular local configuration of segments in concentrated solutions of PMA and PMMA
compared to that of PVAc.
PMID- 26415635
TI - Does LLETZ excision margin status predict residual disease in women who have
undergone post-treatment cervical cytology and high-risk human papillomavirus
testing?
AB - OBJECTIVE: This study looks at the importance of large loop excision of the
transformation zone (LLETZ) excision margins and residual cervical
intraepithelial neoplasia (CIN) in women undertaking high-risk human
papillomavirus (hrHPV) test of cure (TOC). METHODS: A retrospective cohort study
with interval analysis performed June 2007 and June 2012 on all women undertaking
treatment for CIN and subsequent hrHPV TOC 6 months post LLETZ. RESULTS: Final
analysis group comprised 2093 women treated by LLETZ (1396 completely excised;
697 incompletely excised). 298 out of 1794 women (13%) were hrHPV positive at
TOC. Thirty-six women who failed TOC and attended colposcopy had residual CIN. No
statistically significant difference existed between the completely and
incompletely excised groups with regards to the detection of residual CIN at 6
months post-treatment. There was no correlation of margins of excision with hrHPV
status at TOC. The overall cure rate at TOC was 98%. CONCLUSIONS: TOC pathways
recommend subsequent follow-up in primary care. This study identified no safety
issues with TOC pathways. We can no longer assess histological failure rates at
12 months; we, therefore, recommend that this measure of treatment failure be
redefined for post TOC women. It seems time to question the benefits of routine
excision margins reporting, in the absence of invasion, for treated CIN. Future
reporting needs to be reconsidered by the Royal College of Pathologists.
PMID- 26415636
TI - Flexible coherent control of plasmonic spin-Hall effect.
AB - The surface plasmon polariton is an emerging candidate for miniaturizing
optoelectronic circuits. Recent demonstrations of polarization-dependent
splitting using metasurfaces, including focal-spot shifting and unidirectional
propagation, allow us to exploit the spin degree of freedom in plasmonics.
However, further progress has been hampered by the inability to generate more
complicated and independent surface plasmon profiles for two incident spins,
which work coherently together for more flexible and tunable functionalities.
Here by matching the geometric phases of the nano-slots on silver to specific
superimpositions of the inward and outward surface plasmon profiles for the two
spins, arbitrary spin-dependent orbitals can be generated in a slot-free region.
Furthermore, motion pictures with a series of picture frames can be assembled and
played by varying the linear polarization angle of incident light. This spin
enabled control of orbitals is potentially useful for tip-free near-field
scanning microscopy, holographic data storage, tunable plasmonic tweezers, and
integrated optical components.
PMID- 26415637
TI - Gender Influence on Weight Loss After Laparoscopic Sleeve Gastrectomy.
PMID- 26415638
TI - Safety and efficacy of regional citrate anticoagulation in continuous venovenous
hemodialysis in the presence of liver failure: the Liver Citrate Anticoagulation
Threshold (L-CAT) observational study.
AB - INTRODUCTION: Regional citrate anticoagulation (RCA) for continuous renal
replacement therapy is widely used in intensive care units (ICUs). However,
concern exists about the safety of citrate in patients with liver failure (LF).
The aim of this study was to evaluate safety and efficacy of RCA in ICU patients
with varying degrees of impaired liver function. METHODS: In a multicenter,
prospective, observational study, 133 patients who were treated with RCA and
continuous venovenous hemodialysis (RCA-CVVHD) were included. Endpoints for
safety were severe acidosis or alkalosis (pH <=7.2 or >=7.55, respectively) and
severe hypo- or hypercalcemia (ionized calcium <=0.9 or >=1.5 mmol/L,
respectively) of any cause. The endpoint for efficacy was filter lifetime. For
analysis, patients were stratified into three predefined liver function or LF
groups according to their baseline serum bilirubin level (normal liver function
<=2 mg/dl, mild LF >2 to <=7 mg/dl, severe LF >7 mg/dl). RESULTS: We included 48
patients with normal liver function, 43 with mild LF, and 42 with severe LF. LF
was predominantly due to ischemia (39 %) or multiple organ dysfunction syndrome
(27 %). The frequency of safety endpoints in the three patient strata did not
differ: severe alkalosis (normal liver function 2 %, mild LF 0 %, severe LF 5 %;
p = 0.41), severe acidosis (normal liver function 13 %, mild LF 16 %, severe LF
14 %; p = 0.95), severe hypocalcemia (normal liver function 8 %, mild LF 14 %,
severe LF 12 %; p = 0.70), and severe hypercalcemia (0 % in all strata). Only
three patients showed signs of impaired citrate metabolism. Overall filter
patency was 49 % at 72 h. After censoring for stop of the treatment due to non
clotting causes, estimated 72-h filter survival was 96 %. CONCLUSIONS: RCA-CVVHD
can be safely used in patients with LF. The technique yields excellent filter
patency and thus can be recommended as first-line anticoagulation for the
majority of ICU patients. TRIAL REGISTRATION: ISRCTN Registry identifier:
ISRCTN92716512 . Date assigned: 4 December 2008.
PMID- 26415639
TI - MicroRNA let-7e Is a Potential Circulating Biomarker of Acute Stage Ischemic
Stroke.
AB - The aim of this study is to determine the expression levels and clinical
significance of circulating microRNAs (miRNAs), let-7e and miR-338 at different
stages following ischemic stroke (IS). Seventy-two patients with IS at the acute
stage were enrolled and monitored at different stages, and 51 healthy volunteers
were served as the normal controls. Expression of let-7e and miR-338 in serum and
cerebral spinal fluid (CSF) samples was analyzed by real-time quantitative PCR.
The relationship between expression levels of let-7e and miR-338, National
Institutes of Health Stroke Scale (NIHSS) scores, and the levels of serum CRP was
analyzed, respectively. Compared to healthy controls, serum let-7e expression
levels were significantly increased, while serum miR-338 expression levels were
slightly increased in IS patients. Expression levels of Let-7e in serum varied at
different stages in IS patients with the lowest expression in the recover stage
and highest expression in the acute stage. However, serum miR-338 expression in
IS patients was not significantly different in any stage. Compared to healthy
controls and nonacute stages of IS groups, let-7e expression in CSF was markedly
upregulated in IS patients at the acute stage. Different from that of let-7e, miR
338 expression in CSF was upregulated in IS patients only at the subacute stage
but not in the acute stage. Meanwhile, let-7e, which was not significantly
correlated with NIHSS scores (r = 0.29, P > 0.05), was positively correlated with
the serum CRP levels (r = 0.67, P = 0.033). There is no significant correlation
between the miR-338 expression levels and NIHSS scores or serum CRP levels.
Moreover, let-7e, but not miR-338, had a high consistency in expression when
tested both in CSF and serum samples. Finally, serum let-7e showed a specificity
up to 73.4 % and a sensitivity of 82.8 % in IS patients at the acute stage,
whereas serum miR-338 in IS patients showed a specificity up to 53.2 % and a
sensitivity of 71.9 % in the acute stage. Expression levels of let-7e in serum
may serve as a useful noninvasive circulating biomarker for the acute stage of
ischemic stroke.
PMID- 26415640
TI - Pulmonary Vein-to-Pulmonary Artery Ratio is an Echocardiographic Index of
Congestive Heart Failure in Dogs with Degenerative Mitral Valve Disease.
AB - BACKGROUND: Early recognition of left-sided congestive heart failure (CHF) in
dogs with degenerative mitral valve disease (DMVD) is important because it
influences medical therapy, timing of follow-up, and outcome. HYPOTHESIS:
Pulmonary vein diameter-to-pulmonary artery diameter ratio (PV/PA) measured by
echocardiography can predict CHF. ANIMALS: Ninety-eight client-owned dogs, 37
controls, and 61 dogs with DMVD. METHODS: Prospective clinical cohort study.
History, physical examination and Doppler-echocardiography were performed. Dogs
were classified as International Small Animal Cardiac Health Council class I, II
or III. Congestive heart failure was identified in a subset of 56 dogs based on
radiographic findings. The PV/PA was measured in bidimensional (2D) and M-mode by
2 investigators blinded to the radiologists' conclusions. RESULTS: Interobserver
coefficients of variation for PV/PA acquisition and measurement were <10%. The
PV/PA in control dogs was approximately 1 and increased with class of heart
failure. The presence of CHF could be best predicted by measuring PV/PA in 2D
echocardiography (cut-off, 1.7; area under the curve, 0.98; CI, 0.97-0.98; P <
.001) with a sensitivity of 96% and a specificity of 91%. CONCLUSION AND CLINICAL
IMPORTANCE: The PV/PA is a simple and reproducible echocardiographic variable
that increases with class of heart failure and may help discriminate dogs in CHF
from asymptomatic dogs with DMVD. Additional studies are required to determine
whether PV/PA might provide additional information in the integrated
interpretation of Doppler-echocardiographic indices of left ventricular filling
pressures and could be used for rapid assessment of CHF in dogs in a critical
care setting.
PMID- 26415643
TI - Capture myopathy in hooved mammals and human Takotsubo syndrome.
PMID- 26415642
TI - A clinical research pathway towards developing new insights into cardiomyopathy.
PMID- 26415641
TI - Adenoviral vector carrying glial cell-derived neurotrophic factor for direct gene
therapy in comparison with human umbilical cord blood cell-mediated therapy of
spinal cord injury in rat.
AB - STUDY DESIGN: Experimental study. OBJECTIVE: To evaluate the treatment of spinal
cord injury with glial cell-derived neurotrophic factor (GDNF) delivered using an
adenoviral vector (AdV-GDNF group) in comparison with treatment performed using
human umbilical cord blood mononuclear cells (UCB-MCs)-transduced with an
adenoviral vector carrying the GDNF gene (UCB-MCs+AdV-GDNF group) in rat.
SETTING: Kazan, Russian Federation. METHODS: We examined the efficacy of AdV-GDNF
and UCB-MCs+AdV-GDNF therapy by conducting behavioral tests on the animals and
morphometric studies on the spinal cord, performing immunofluorescence analyses
on glial cells, investigating the survival and migration potential of UCB-MCs,
and evaluating the expression of the recombinant GDNF gene. RESULTS: At the 30th
postoperative day, equal positive locomotor recovery was observed after both
direct and cell-based GDNF therapy. However, after UCB-MCs-mediated GDNF therapy,
the area of preserved tissue and the number of spared myelinated fibers were
higher than those measured after direct GDNF gene therapy. Moreover, we observed
distinct changes in the populations of glial cells; expression patterns of the
specific markers for astrocytes (GFAP, S100B and AQP4), oligodendrocytes
(PDGFalphaR and Cx47) and Schwann cells (P0) differed in various areas of the
spinal cord of rats treated with AdV-GDNF and UCB-MCs+AdV-GDNF. CONCLUSION: The
differences detected in the AdV-GDNF and UCB-MCs+AdV-GDNF groups could be
partially explained by the action of UCB-MCs. We discuss the insufficiency and
the advantages of these two methods of GDNF gene delivery into the spinal cord
after traumatic injury.
PMID- 26415644
TI - Regulation of secondary metabolite production in the fungal tomato pathogen
Cladosporium fulvum.
AB - Cladosporium fulvum is a non-obligate biotrophic fungal tomato pathogen for which
fifteen secondary metabolite (SM) gene clusters were previously identified in its
genome. However, most of these SM biosynthetic pathways remain cryptic during
growth in planta and in different in vitro conditions. The sole SM produced in
vitro is the pigment cladofulvin. In this study, we attempted to activate cryptic
pathways in order to identify new compounds produced by C. fulvum. For this
purpose, we manipulated orthologues of the global regulators VeA, LaeA and HdaA
known to regulate SM biosynthesis in other fungal species. In C. fulvum, deleting
or over-expressing these regulators yielded no new detectable SMs. Yet,
quantification of cladofulvin revealed that CfHdaA is an activator whilst CfVeA
and CfLaeA seemed to act as repressors of cladofulvin production. In the wild
type strain, cladofulvin biosynthesis was affected by the carbon source, with
highest production under carbon limitation and traces only in presence of
saccharose. Repression of cladofulvin production by saccharose was dependent on
both CfVeA and CfLaeA. Deletion of CfVeA or CfLaeA caused production of sterile
mycelia, whilst Deltacfhdaa deletion mutants sporulated, suggesting that
cladofulvin production is not linked to asexual reproduction. Profiling the
transcription of these regulators showed that CfHdaA-mediated regulation of
cladofulvin production is independent of both CfVeA and CfLaeA. Our data suggest
CfLaeA directly affects cladofulvin production whilst the effect of CfVeA is
indirect, suggesting a role for CfLaeA outside of the Velvet complex. In
conclusion, our results showed that regulation of SM production in C. fulvum is
different from other fungi and indicate that manipulation of global regulators is
not a universal tool to discover new fungal natural products.
PMID- 26415645
TI - Temperature/pH Responsive Hydrogels Based on Poly(ethylene glycol) and
Functionalized Poly(e-caprolactone) Block Copolymers for Controlled Delivery of
Macromolecules.
AB - PURPOSE: To assess the potential of triblock copolymers based on poly(ethylene
glycol) (PEG) and functionalized poly(epsilon-caprolactone) as temperature/pH
responsive gels for controlled delivery of macromolecules. METHODS: Poly(alpha
carboxylate-co-alpha-benzylcarboxylate-epsilon-caprolactone)-PEG-poly(alpha
carboxylate-co-alpha-benzylcarboxylate-epsilon-caprolactone) (PCBCL-PEG-PCBCL)
was synthesized through ring opening polymerization of alpha-benzyl carboxylate
epsilon-caprolactone by PEG, followed by 30% debenzylation of the lateral blocks.
The effect of Tris buffer and pH on the sol-gel transition temperature of PCBCL
PEG-PCBCL was assessed. The temperature/pH responsive release of
tetramethylrhodamine-dextran (TMR-D) (10 and 40 kDa) from PCBCL-PEG-PCBCL was
investigated. RESULTS: Replacement of water with Tris buffer reduced PCBCL-PEG
PCBCL sol-gel transition temperature. Thermo-reversible hydrogels were only
formed at pHs >= 5.0, but PCBCL-PEG-PCBCL transition temperature was not affected
by pH above pH 5.0. In contrast to Pluronic F127 that released 100% of TMR-D
within 2 h, PCBCL-PEG-PCBCL hydrogel controlled TMR-D release efficiently at pH =
7.4 and 37 degrees C (~27 and 11% TMRD 10 and 40 kDa release within 150 h,
respectively). At 50 degrees C or pH = 9.0, TMR-D release was increased slightly,
while at room temperature or pH = 5.0, no control over TMR-D release was observed
by PCBCL-PEG-PCBCL hydrogel. CONCLUSION: PCBCL-PEG-PCBCL hydrogel provides depot
release of macromolecules at physiological conditions. This release can be
triggered through changes in the temperature or pH.
PMID- 26415646
TI - Modulation of Cell-Mediated Immunity to Suppress High Fat Diet-Induced Obesity
and Insulin Resistance.
AB - PURPOSE: To assess the effect of immune modulators, cyclosporin A and fingolimod,
on high fat diet-induced obesity and insulin resistance. METHODS: C57BL/6 mice
were fed a high fat diet and injected intraperitoneally with cyclosporine A,
fingolimod, or vehicle twice weekly for 15 weeks. Body weight and food intake
were manually measured every other day. Glucose tolerance test, insulin
sensitivity, and body composition were examined and compared between the control
and the immune modulator treated animals. Tissue samples were collected at the
end of the experiment and examined for serum biochemistry, histology, and mRNA
levels of marker genes for inflammation, and glucose and lipid metabolism in
white and brown adipose tissues and in the liver. RESULTS: Cyclosporine A and
fingolimod suppressed high fat diet-induced weight gain, reduced hepatic fat
accumulation, and improved insulin sensitivity. The beneficial effects are
associated with altered expression of F4/80, Cd68, Il-6, Tnf-alpha, and Mcp-1
genes, which are involved in macrophage-related chronic inflammation in adipose
and hepatic tissues. CONCLUSION: Immune modulation represents an important
intervention for obesity and obesity-associated insulin resistance.
PMID- 26415648
TI - Plic-1, a new target in repressing epileptic seizure by regulation of GABAAR
function in patients and a rat model of epilepsy.
AB - Dysfunction of gamma-aminobutyric acid A (GABAA) receptors (GABAARs) is a
prominent factor affecting intractable epilepsy. Plic-1, an ubiquitin-like
protein enriched in the inhibitory synapses connecting GABAARs and the ubiquitin
protease system (UPS), plays a key role in the modification of GABAAR functions.
However, the relationship between Plic-1 and epileptogenesis is not known. In the
present study, we aimed to investigate Plic-1 levels in patients with temporal
lobe epilepsy, as well as the role of Plic-1 in regulating onset and progression
of epilepsy in animal models. We found that Plic-1 expression was significantly
decreased in patients with epilepsy as well as pilocarpine- and pentylenetetrazol
(PTZ)-induced rat epileptic models. Intrahippocampal injection of the PePalpha
peptide, which disrupts Plic-1 binding to GABAARs, significantly shortened the
latency of seizure onset, and increased the seizure severity and duration in
these two epileptic models. Overexpressed Plic-1 through lentivirus transfection
into a PTZ model resulted in a reduction in both seizure severity and generalized
tonic-clonic seizure duration. Whole-cell clamp recordings revealed that the
PePalpha peptide decreased miniature inhibitory postsynaptic currents (mIPSCs)
whereas overexpressed Plic-1 increased mIPSCs in the pyramidal neurons of the
hippocampus. These effects can be blocked by picrotoxin, a GABAAR inhibitor. Our
results indicate that Plic-1 plays an important role in managing epileptic
seizures by enhancing seizure inhibition through regulation of GABAARs at
synaptic sites.
PMID- 26415647
TI - Predicting Mouse Liver Microsomal Stability with "Pruned" Machine Learning Models
and Public Data.
AB - PURPOSE: Mouse efficacy studies are a critical hurdle to advance translational
research of potential therapeutic compounds for many diseases. Although mouse
liver microsomal (MLM) stability studies are not a perfect surrogate for in vivo
studies of metabolic clearance, they are the initial model system used to assess
metabolic stability. Consequently, we explored the development of machine
learning models that can enhance the probability of identifying compounds
possessing MLM stability. METHODS: Published assays on MLM half-life values were
identified in PubChem, reformatted, and curated to create a training set with 894
unique small molecules. These data were used to construct machine learning models
assessed with internal cross-validation, external tests with a published set of
antitubercular compounds, and independent validation with an additional diverse
set of 571 compounds (PubChem data on percent metabolism). RESULTS: "Pruning" out
the moderately unstable / moderately stable compounds from the training set
produced models with superior predictive power. Bayesian models displayed the
best predictive power for identifying compounds with a half-life >=1 h.
CONCLUSIONS: Our results suggest the pruning strategy may be of general benefit
to improve test set enrichment and provide machine learning models with enhanced
predictive value for the MLM stability of small organic molecules. This study
represents the most exhaustive study to date of using machine learning approaches
with MLM data from public sources.
PMID- 26415649
TI - miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and
SMAD7.
AB - The cytokine transforming growth factor (TGF)-beta1 plays a central role in
diabetic nephropathy (DN) with data implicating the miRNA (miR) miR-21 as a key
modulator of its prosclerotic actions. In the present study, we demonstrate data
indicating that miR-21 up-regulation positively correlates with the severity of
fibrosis and rate of decline in renal function in human DN. Furthermore,
concomitant analyses of various models of fibrotic renal disease and experimental
DN, confirm tubular miR-21 up-regulation. The fibrotic changes associated with
increased miR-21 levels are proposed to include the regulation of TGF-beta1
mediated mothers against decapentaplegic homolog 3 (SMAD3)- and phosphoinositide
3-kinase (PI3K)-dependent signalling pathways via co-ordinated repression of
mothers against decapentaplegic homolog 7 (SMAD7) and phosphatase and tensin
homologue (PTEN) respectively. This represents a previously uncharacterized
interaction axis between miR-21 and PTEN-SMAD7. Targeting of these proteins by
miR-21 resulted in de-repression of the respective pathways as reflected by
increases in SMAD3 and V-Akt murine thymoma viral oncogene homolog 1 (AKT)
phosphorylation. Many of the changes typically induced by TGF-beta1, including
phosphorylation of signalling mediators, were further enhanced by miR-21.
Collectively, these data present a unified model for a key role for miR-21 in the
regulation of renal tubular extracellular matrix (ECM) synthesis and accumulation
and provide important insights into the molecular pathways implicated in the
progression of DN.
PMID- 26415650
TI - Assembly and Function of the Precursor B-Cell Receptor.
AB - During early stages of development, precursor B lymphocytes express a
characteristic type of antigen receptor known as the pre-B-cell receptor (pre
BCR). This receptor differs from conventional BCRs in that it possesses a germ
line-encoded surrogate light chain (SLC), which is associated with the signal
transduction machinery via heavy chain (HC) proteins that have been generated by
productive rearrangement of the immunoglobulin HC genes. The pre-BCR marks a key
step of B-cell commitment, as it activates the B-cell-specific signaling cascade
and mediates the selection, expansion, and differentiation of cells expressing a
productively rearranged HC protein. Another difference between the pre-BCR and
conventional BCR might be the initial event that triggers receptor activation, as
the pre-BCR is activated in the absence of external ligands, while conventional
BCRs require antigen for activation. Nonetheless, the pre-BCR downstream
signaling cascade is largely similar to that of the BCR suggesting that the
characteristic LC of the pre-BCR mediates important receptor interactions thereby
providing distinctive, germ line-encoded features to the pre-BCR. In fact, the
SLC enables the pre-BCR to act as a surrogate autoreactive receptor. Here, we
outline the structure and function of the pre-BCR and how the autonomous
signaling capacity might be a direct consequence of pre-BCR assembly. In addition
to its role in early B-cell development, we discuss how the ordered activation of
downstream signaling cascades enables the pre-BCR to activate seemingly opposing
cellular programs such as proliferation and differentiation.
PMID- 26415651
TI - Erratum to: The association between CYP1A1 genetic polymorphisms and coronary
artery disease in the Uygur and Han of China.
PMID- 26415652
TI - Structural comparison of O-antigen gene clusters of Legionella pneumophila and
its application of a serogroup-specific multiplex PCR assay.
AB - The Legionella pneumophila serogroups O1, O4, O6, O7, O10 and O13 are pathogenic
strains associated with pneumonia. The surface O-antigen gene clusters of L.
pneumophila serogroups O4, O6, O7, O10 and O13 were sequenced and analyzed, with
the function annotated on the basis of homology to that of the genes of L.
pneumophila serogroup O1 (L. pneumophila subsp. pneumophila str. Philadelphia 1).
The gene locus of the six L. pneumophila serogroups contains genes of yvfE,
neuABCD, pseA-like for nucleotide sugar biosynthesis, wecA for sugar transfer,
and wzm as well as wzt for O-antigen processing. The detection of O-antigen genes
allows the fine differentiation at species and serogroup level without the
neccessity of nucleotide sequencing. The O-antigen-processing genes wzm and wzt,
which were found to be distinctive for different for different serogroups, have
been used as the target genes for the detection and identification of L.
pneumophila strains of different O serogroups. In this report, a multiplex PCR
assay based on wzm or wzt that diferentiates all the six serogroups by amplicon
size was developed with the newly designed specific primer pairs for O1 and O7,
and the specific primer pairs for O4, O6, O10, and O13 reported previously. The
array was validated by analysis of 34 strains including 15 L. pneumophila O
standard reference strains, eight reference strains of other Legionella non
pneumophila species, six other bacterial species, and five L. pneumophila
environmental isolates. The detection sensitivity was one ng genomic DNA. The
accurate and sensitive assay is suitable for the identification and detection of
strains of these serogroups in environmental and clinical samples.
PMID- 26415653
TI - Detection of chlorine and bromine in free liquid from the sphenoid sinus as an
indicator of seawater drowning.
AB - We have investigated the usefulness of elemental analysis by energy-dispersive X
ray spectroscopy (EDX) in the examination of free liquid from the sphenoid sinus
of drowning victims. We detected both chlorine and bromine in liquid taken from
the sphenoid sinus of seawater drowning victims. Because these elements were
below the quantification limit in freshwater cases, we could easily distinguish
seawater from freshwater drowning cases. Detection of these elements from the
liquid in the sphenoid sinuses of drowning victims may be useful as a supportive
measure for seawater drowning.
PMID- 26415654
TI - With reference to the letter to the editor by Henssge (Leg Med (Tokyo). 2015 Jul
29. http://dx.doi.org/10.1016/j.legalmed.2015.05.005.): "'With reference to the
article by Hubig et al.: Temperature based forensic death time estimation: The
standard model in experimental test' (Legal Med 2015 XX)".
PMID- 26415655
TI - Allele frequencies for 21 autosomal short tandem repeat loci obtained using
GlobalFiler in a sample of 1501 individuals from the Japanese population.
AB - Allele frequencies for 21 autosomal short tandem repeat loci (D3S1358, vWA,
D16S539, CSF1PO, TPOX, D8S1179, D21S11, D18S51, D2S441, D19S433, TH01, FGA,
D22S1045, D5S818, D13S317, D7S820, SE33, D10S1248, D1S1656, D12S391, and D2S1338)
were obtained using the GlobalFiler kit from 1501 unrelated individuals sampled
from the Japanese population.
PMID- 26415656
TI - Vertical transport in graphene-hexagonal boron nitride heterostructure devices.
AB - Research in graphene-based electronics is recently focusing on devices based on
vertical heterostructures of two-dimensional materials. Here we use density
functional theory and multiscale simulations to investigate the tunneling
properties of single- and double-barrier structures with graphene and few-layer
hexagonal boron nitride (h-BN) or hexagonal boron carbon nitride (h-BC2N). We
find that tunneling through a single barrier exhibit a weak dependence on energy.
We also show that in double barriers separated by a graphene layer we do not
observe resonant tunneling, but a significant increase of the tunneling
probability with respect to a single barrier of thickness equal to the sum of the
two barriers. This is due to the fact that the graphene layer acts as an
effective phase randomizer, suppressing resonant tunneling and effectively
letting a double-barrier structure behave as two single-barriers in series.
Finally, we use multiscale simulations to reproduce a current-voltage
characteristics resembling that of a resonant tunneling diode, that has been
experimentally observed in single barrier structure. The peak current is obtained
when there is perfect matching between the densities of states of the cathode and
anode graphene regions.
PMID- 26415657
TI - Steroid Sulfatase Inhibitors Based on Phosphate and Thiophosphate Flavone
Analogs.
AB - A series of phosphate and thiophosphate flavone derivatives were synthesized and
biologically evaluated in vitro for inhibition of steroid sulfatase (STS)
activity. The described synthesis includes the straightforward preparation of 7
hydroxy-2-phenyl-4H-chromen-4-one 3a, 2-(4-fluorophenyl)-7-hydroxy-4H-chromen-4
one 3b, 7-hydroxy-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one 3c, 7-hydroxy-2
(p-tolyl)-4H-chromen-4-one 3d modified with different phosphate or thiophosphate
moieties. The inhibitory properties of the synthesized compounds were tested
against human placenta STS. Some of the novel STS inhibitors had good activities
against STS. In particular, the bis-(4-oxo-2-(p-tolyl)-4H-chromen-7-yl)
hydrogenthiophosphate, 6i had the most potent inhibitory effect with an IC50
value of 3.25 uM as compared to an IC50 value of 8.50 uM for the 2-(4
trifluoromethylphenyl)-chromen-4-one-7-O-sulfamate used as a reference.
PMID- 26415658
TI - Complete genome sequence of Lactobacillus paracasei L9, a new probiotic strain
with high lactic acid-producing capacity.
AB - Lactobaillus paracasei L9 (CGMCC No. 9800) is a new strain with probiotic
properties originating from healthy human intestine. Previous studies evidenced
that the strain regulates immune modulation and contributes to the production of
high amounts of lactic acid. The genome of L. paracasei L9 contains a circular
3076,437-bp chromosome, encoding 3044 CDSs, 15 rRNA genes and 59 tRNA genes.
PMID- 26415659
TI - Complete genome sequence of Arthrobacter sp. ERGS1:01, a putative novel bacterium
with prospective cold active industrial enzymes, isolated from East Rathong
glacier in India.
AB - We report the complete genome sequence of Arthrobacter sp. ERGS1:01, a novel
bacterium which produces industrial enzymes at low temperature. East Rathong
glacier in Sikkim Himalayas is untouched and unexplored for microbial diversity
though it has a rich source of glaciers, alpine and meadows. Genome sequence has
provided the basis for understanding its adaptation under harsh condition of
Himalayan glacier, its ability to produce cold active industrial enzymes and has
unlocked opportunities for microbial bioprospection from East Rathong glacier.
PMID- 26415660
TI - Complete genome sequence of Photorhabdus temperata subsp. thracensis 39-8 T, an
entomopathogenic bacterium for the improved commercial bioinsecticide.
AB - Photorhabdus temperata subsp. thracensis 39-8(T), a symbiotic bacterium from an
entomopathogenic nematode Heterorhabditis bacteriophora, is a novel bacterium
harboring insect pathogenicity. Herein, we present the complete genome sequence
of strain 39-8(T), which consists of one circular chromosome of 5,147,098 bp with
a GC content of 44.10%. This genetic information will provide insights into
biotechnological applications of the genus Photorhabdus producing insecticidal
toxins, leading to the enhanced commercial bioinsecticide in agricultural pest
control.
PMID- 26415661
TI - CATCHing putative causative variants in consanguineous families.
AB - BACKGROUND: Consanguinity is an important risk factor for autosomal recessive
(AR) disorders. Extended genomic regions identical by descent (IBD) in the
offspring of consanguineous parents give rise to recessive disorders with
identical (homozygous) pathogenic variants in both alleles. However, many
clinical phenotypes presenting in the offspring of consanguineous couples are
still of unknown etiology. Nowadays advances in High Throughput Sequencing
provide an excellent opportunity to achieve a molecular diagnosis or to identify
novel candidate genes. RESULTS: To exploit all available information from the
family structure we developed CATCH, an algorithm that combines genotyped SNPs of
all family members for the optimal detection of Runs Of Homozygosity (ROH) and
exome sequencing data from one affected individual to identify putative causative
variants in consanguineous families. CONCLUSIONS: CATCH proved to be effective in
discovering known or putative new causative variants in 43 out of 50
consanguineous families. Among them, novel variants causative of familial
thrombocytopenia, sclerosis bone dysplasia and the first homozygous loss-of
function mutation in FGFR3 in human causing severe skeletal deformities, tall
stature and hearing impairment were identified.
PMID- 26415662
TI - Phenothiazines as a solution for multidrug resistant tuberculosis: From the
origin to present.
AB - Historically, multiplicity of actions in synthetic compounds is a rule rather
than exception. The science of non-antibiotics evolved in this background. From
the antimalarial and antitrypanosomial dye methylene blue, chemically similar
compounds, the phenothiazines, were developed. The phenothiazines were first
recognised for their antipsychotic properties, but soon after their antimicrobial
functions came to be known and then such compounds were designated as non
antibiotics. The emergence of highly drug-resistant bacteria had initiated an
urgent need to search for novel affordable compounds. Several phenothiazines
awakened the interest among scientists to determine their antimycobacterial
activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were
found to have distinct antitubercular action. Thioridazine took the lead as
researchers repeatedly claimed its potentiality. Although thioridazine is known
for its central nervous system and cardiotoxic side-effects, extensive and
repeated in vitro and in vivo studies by several research groups revealed that a
very small dose of thioridazine is required to kill tubercle bacilli inside
macrophages in the lungs, where the bacteria try to remain and multiply silently.
Such a small dose is devoid of its adverse side-effects. Recent studies have
shown that the (-) thioridazine is a more active antimicrobial agent and devoid
of the toxic side effects normally encountered. This review describes the
possibilities of bringing down thioridazine and its (-) form to be combined with
other antitubercular drugs to treat infections by drug-resistant strains of
Mycobacterium tuberculosis and try to eradicate this deadly disease.
PMID- 26415663
TI - Combined use of a new SNP-based assay and multilocus SSR markers to assess
genetic diversity of Xylella fastidiosa subsp. pauca infecting citrus and coffee
plants.
AB - Two haplotypes of Xylella fastidiosa subsp. pauca (Xfp) that correlated with
their host of origin were identified in a collection of 90 isolates infecting
citrus and coffee plants in Brazil, based on a single-nucleotide polymorphism in
the gyrB sequence. A new single-nucleotide primer extension (SNuPE) protocol was
designed for rapid identification of Xfp according to the host source. The
protocol proved to be robust for the prediction of the Xfp host source in blind
tests using DNA from cultures of the bacterium, infected plants, and insect
vectors allowed to feed on Xfp-infected citrus plants. AMOVA and STRUCTURE
analyses of microsatellite data separated most Xfp populations on the basis of
their host source, indicating that they were genetically distinct. The combined
use of the SNaPshot protocol and three previously developed multilocus SSR
markers showed that two haplotypes and distinct isolates of Xfp infect citrus and
coffee in Brazil and that multiple, genetically different isolates can be present
in a single orchard or infect a single tree. This combined approach will be very
useful in studies of the epidemiology of Xfp-induced diseases, host specificity
of bacterial genotypes, the occurrence of Xfp host jumping, vector feeding
habits, etc., in economically important cultivated plants or weed host reservoirs
of Xfp in Brazil and elsewhere.
PMID- 26415665
TI - Use of E-beam radiation to eliminate Listeria monocytogenes from surface mould
cheese.
AB - Camembert and Brie soft cheese varieties were subjected to E-beam irradiation as
a sanitation treatment. The effects of treatments on microbiota and selected
physicochemical properties were also studied. The absorbed doses required to meet
the food safety objective (FSO) according to EU and USDA criteria for Listeria
monocytogenes were 1.27 and 2.59 kGy, respectively. The bacterial load, mainly
lactic acid bacteria, was reduced by the treatment but injured cells were
recovered during storage at 14 degrees C. The radiation treatment gave rise to
negligible changes in the pH and water activity at doses required to achieve
microbial safety.
PMID- 26415664
TI - Strong correlation between the antifungal effect of amphotericin B and its
inhibitory action on germ-tube formation in a Candida albicans URA+ strain.
AB - The hypothetical capacity of amphotericin B to suppress the formation of germ
tubes, which is the first step of yeast-to-hypha conversion in Candida albicans,
has been investigated in the wild-type strain CEY.1 (CAI.4-URA+). Exponential
cells exposed to concentrations of amphotericin B below or around the MIC90,
exhibited a weak reduction in the percentage of human serum-induced germ-tube
formation at 37oC compared with a non-exposed control. However, the dimorphic
transition was drastically suppressed after addition of potentially lethal doses
of amphotericin B, which also caused severe cell killing. In contrast, an
identical experimental approach carried out with the fungistatic compound 5
fluorocytosine had no significant effect on the level of the germ-tube formation.
Together, these results strongly point to a close correlation between the
fungicidal action of amphotericin B and its ability to impair morphogenetic
conversion in C. albicans.
PMID- 26415666
TI - Solar water disinfection (SODIS): Impact on hepatitis A virus and on a human
Norovirus surrogate under natural solar conditions.
AB - This study evaluates the effectiveness of solar water disinfection (SODIS) in the
reduction and inactivation of hepatitis A virus (HAV) and of the human Norovirus
surrogate, murine Norovirus (MNV-1), under natural solar conditions. Experiments
were performed in 330 ml polyethylene terephthalate (PET) bottles containing HAV
or MNV-1 contaminated waters (10(3) PFU/ml) that were exposed to natural sunlight
for 2 to 8 h. Parallel experiments under controlled temperature and/or in
darkness conditions were also included. Samples were concentrated by
electropositive charged filters and analysed by RT-real time PCR (RT-qPCR) and
infectivity assays. Temperature reached in bottles throughout the exposure period
ranged from 22 to 40oC. After 8 h of solar exposure (cumulative UV dose of ~828
kJ/m2 and UV irradiance of ~20 kJ/l), the results showed significant (P<0.05)
reductions from 4.0 (+/-0.56)x10(4) to 3.15 (+/-0.69)x10(3) RNA copies/100ml
(92.1%, 1.1 log) for HAV and from 5.91 (+/-0.59)x10(4) to 9.24 (+/-3.91)x10(3)
RNA copies/100 ml (84.4%, 0.81 log) for MNV-1. SODIS conditions induced a loss of
infectivity between 33.4% and 83.4% after 4 to 8 h in HAV trials, and between
33.4% and 66.7% after 6 h to 8 h in MNV-1 trials. The results obtained indicated
a greater importance of sunlight radiation over the temperature as the main
factor for viral reduction.
PMID- 26415667
TI - Increasing antibiotic resistance in preservative-tolerant bacterial strains
isolated from cosmetic products.
AB - To ensure the microbiological quality, consumer safety and organoleptic
properties of cosmetic products, manufacturers need to comply with defined
standards using several preservatives and disinfectants. A drawback regarding the
use of these preservatives is the possibility of generating cross
insusceptibility to other disinfectants or preservatives, as well as cross
resistance to antibiotics. Therefore, the objective of this study was to
understand the adaptive mechanisms of Enterobacter gergoviae, Pseudomonas putida
and Burkholderia cepacia that are involved in recurrent contamination in cosmetic
products containing preservatives. Diminished susceptibility to formaldehyde
donors was detected in isolates but not to other preservatives commonly used in
the cosmetics industry, although increasing resistance to different antibiotics
(beta-lactams, quinolones, rifampicin, and tetracycline) was demonstrated in
these strains when compared with the wild-type strain. The outer membrane protein
modifications and efflux mechanism activities responsible for the resistance
trait were evaluated. The development of antibiotic-resistant microorganisms due
to the selective pressure from preservatives included in cosmetic products could
be a risk for the emergence and spread of bacterial resistance in the
environment. Nevertheless, the large contribution of disinfection and
preservation cannot be denied in cosmetic products.
PMID- 26415668
TI - Properties of Lactobacillus reuteri chitosan-calcium-alginate encapsulation under
simulated gastrointestinal conditions.
AB - The protective effects of encapsulation on the survival of Lactobacillus reuteri
and the retention of the bacterium's probiotic properties under simulated
gastrointestinal conditions were investigated. Viable counts and the remaining
probiotic properties of calcium (Ca)-alginate encapsulated (A group), chitosan-Ca
alginate encapsulated (CA group), and unencapsulated, free L. reuteri (F group)
were determined. Encapsulation improved the survival of L. reuteri subjected to
simulated gastrointestinal conditions, with the greatest protective effect
achieved in the CA group. The degree of cell membrane injury increased with
increasing bile salt concentrations at constant pH, but the extent of injury was
less in the encapsulated than in the free cells. Adherence rates were, in
descending order: CA (0.524%)>A (0.360%)>F (0.275%). Lactobacillus reuteri cells
retained their antagonistic activity toward Listeria monocytogenes even after
incubation of the lactobacilli under simulated gastrointestinal conditions.
Displacement of the pathogen by cells released from either of the encapsulation
matrices was higher than that by free cells. The safety of L. reuteri was
demonstrated in an in vitro invasion assay.
PMID- 26415669
TI - Pulmonary sarcoidosis is associated with high-level inducible co-stimulator
(ICOS) expression on lung regulatory T cells--possible implications for the
ICOS/ICOS-ligand axis in disease course and resolution.
AB - Sarcoidosis is a granulomatous inflammatory disorder of unknown aetiology. The
increased frequency of activated lung CD4(+) T cells with a T helper type 1 (Th1)
cytokine profile in sarcoidosis patients is accompanied by a reduced proportion
and/or impaired function of regulatory T cells (Tregs ). Here we evaluated the
expression of the inducible co-stimulator (ICOS) on lung and blood CD4(+) T cell
subsets in sarcoidosis patients with different prognosis, by flow cytometry.
Samples from the deep airways were obtained by bronchoalveolar lavage (BAL). We
show that Tregs from the inflamed lung of sarcoidosis patients were characterized
by a unique ICOS(high) phenotype. High-level ICOS expression was restricted to
Tregs from the inflamed lung and was absent in blood Tregs of sarcoidosis
patients as well as in lung and blood Tregs of healthy volunteers. In addition,
lung Tregs exhibited increased ICOS expression compared to sarcoid-specific lung
effector T cells. Strikingly, ICOS expression on Tregs was in particularly high
in the lungs of Lofgren's syndrome (LS) patients who present with acute disease
which often resolves spontaneously. Moreover, blood monocytes from LS patients
revealed increased ICOS-L levels compared to healthy donors. Sarcoidosis was
associated with a shift towards a non-classical monocyte phenotype and the ICOS
L(high) phenotype was restricted to this particular monocyte subset. We propose a
potential implication of the ICOS/ICOS-L immune-regulatory axis in disease
activity and resolution and suggest to evaluate further the suitability of ICOS
as biomarker for the prognosis of sarcoidosis.
PMID- 26415670
TI - Investigating the influence of KIBRA and CLSTN2 genetic polymorphisms on cross
sectional and longitudinal measures of memory performance and hippocampal volume
in older individuals.
AB - The variability of episodic memory decline and hippocampal atrophy observed with
increasing age may partly be explained by genetic factors. KIBRA (kidney and
brain expressed protein) and CLSTN2 (calsyntenin 2) are two candidate genes
previously linked to episodic memory performance and volume of the hippocampus, a
key memory structure. However, whether polymorphisms in these two genes also
influence age-related longitudinal memory decline and hippocampal atrophy is
still unknown. Using data from two independent cohorts, the Sydney Memory and
Ageing Study and the Older Australian Twins Study, we investigated whether the
KIBRA and CLSTN2 genetic polymorphisms (rs17070145 and rs6439886) are associated
with episodic memory performance and hippocampal volume in older adults (65-90
years at baseline). We were able to examine these polymorphisms in relation to
memory and hippocampal volume using cross-sectional data and, more importantly,
also using longitudinal data (2 years between testing occasions). Overall we did
not find support for an association of KIBRA either alone or in combination with
CLSTN2 with memory performance or hippocampal volume, nor did variation in these
genes influence longitudinal memory decline or hippocampal atrophy in two cohorts
of older adults.
PMID- 26415672
TI - Nanoparticle shape anisotropy and photoluminescence properties: Europium
containing ZnO as a Model Case.
AB - The precise control over electronic and optical properties of semiconductor (SC)
materials is pivotal for a number of important applications like in
optoelectronics, photocatalysis or in medicine. It is well known that the
incorporation of heteroelements (doping as a classical case) is a powerful method
for adjusting and enhancing the functionality of semiconductors. Independent from
that, there already has been a tremendous progress regarding the synthesis of
differently sized and shaped SC nanoparticles, and quantum-size effects are well
documented experimentally and theoretically. Whereas size and shape control of
nanoparticles work fairly well for the pure compounds, the presence of a
heteroelement is problematic because the impurities interfere strongly with
bottom up approaches applied for the synthesis of such particles, and effects are
even stronger, when the heteroelement is aimed to be incorporated into the target
lattice for chemical doping. Therefore, realizing coincident shape control of
nanoparticle colloids and their doping still pose major difficulties. Due to a
special mechanism of the emulsion based synthesis method presented here,
involving a gelation of emulsion droplets prior to crystallization of shape
anisotropic ZnO nanoparticles, heteroelements can be effectively entrapped inside
the lattice. Different nanocrystal shapes such as nanorods, -prisms, -plates, and
-spheres can be obtained, determined by the use of certain emulsification agents.
The degree of morphologic alterations depends on the type of incorporated
heteroelement M(n+), concentration, and it seems that some shapes are more
tolerant against doping than others. Focus was then set on the incorporation of
Eu(3+) inside the ZnO particles, and it was shown that nanocrystal shape and
aspect ratios could be adjusted while maintaining a fixed dopant level. Special
PL properties could be observed implying energy transfer from ZnO excited near
its band-gap (3.3 eV) to the Eu(3+) states mediated by defect luminescence of the
nanoparticles. Indications for an influence of shape on photoluminescence (PL)
properties were found. Finally, rod-like Eu@ZnO colloids were used as tracers to
investigate their uptake into biological samples like HeLa cells. The PL was
sufficient for identifying green and red emission under visible light excitation.
PMID- 26415671
TI - Error-related brain activity dissociates hoarding disorder from obsessive
compulsive disorder.
AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with an abnormally
large error-related negativity (ERN), an electrophysiological measure of error
monitoring in response to performance errors, but it is unclear if hoarding
disorder (HD) also shows this abnormality. This study aimed to determine whether
the neurophysiological mechanisms underlying error monitoring are similarly
compromised in HD and OCD. METHOD: We used a visual flanker task to assess ERN in
response to performance errors in 14 individuals with HD, 27 with OCD, 10 with
HD+OCD, and 45 healthy controls (HC). Age-corrected performance and ERN
amplitudes were examined using analyses of variance and planned pairwise group
comparisons. RESULTS: A main effect of hoarding on ERN (p = 0.031) was observed,
indicating ERN amplitudes were attenuated in HD relative to non-HD subjects. A
group * age interaction effect on ERN was also evident. In HD-positive subjects,
ERN amplitude deficits were significantly greater in younger individuals (r =
0.479, p = 0.018), whereas there were no significant ERN changes with increasing
age in OCD and HC participants. CONCLUSIONS: The reduced ERN in HD relative to
OCD and HC provides evidence that HD is neurobiologically distinct from OCD, and
suggests that deficient error monitoring may be a core pathophysiological feature
of HD. This effect was particularly prominent in younger HD participants, further
suggesting that deficient error monitoring manifests most strongly early in the
illness course and/or in individuals with a relatively early illness onset.
PMID- 26415673
TI - The relationships between illness and treatment perceptions with adherence to
diabetes self-care: A comparison between Arabic-speaking migrants and Caucasian
English-speaking patients.
AB - AIMS: To compare illness and treatment perceptions between Arabic-speaking
immigrants and Caucasian English-speaking people with type 2 diabetes, and
explore the relationships between these beliefs and adherence to self-care
activities. METHODS: A cross-sectional study was conducted in healthcare settings
with large Arabic populations in metropolitan and rural Victoria, Australia.
Adherence to self-care activities, illness and treatment perceptions, and
clinical data were recorded. Bivariate associations for continuous normally
distributed variables were tested with Pearson's correlation. Non-parametric data
were tested using Spearman's rank correlation coefficient. RESULTS: 701
participants were recruited; 392 Arabic-speaking participants (ASPs) and 309
English-speaking participants (ESPs). There were significant relationships
between participants' illness and treatment perceptions and adherence to diabetes
self-care activities. ASPs' negative beliefs about diabetes were strongly and
significantly correlated with poorer adherence to diet recommendations, exercise,
blood glucose testing and foot care. ASPs were significantly less adherent to all
aspects of diabetes self-care compared with ESPs: dietary behaviours (P=<0.01;
95% confidence interval (CI)=-1.17, -0.84), exercise and physical activity
(P=<0.001, 95% CI -1.14, -0.61), blood glucose testing (P=<0.001) and foot-care
(P=<0.001). 52.8% of ASPs were sceptical about prescribed diabetes treatment
compared with only 11.2% of the ESPs. 88.3% of ASPs were non-adherent to
prescribed medication, compared with 45.1% of ESPs. CONCLUSIONS: Arabic-speaking
migrants' illness and treatment perceptions were significantly different from the
English-speaking group. There is a pressing need to develop new innovative
interventions that deliver much-needed improvements in adherence to self-care
activities and key health outcomes.
PMID- 26415674
TI - Many parallels between itch and pain research.
PMID- 26415675
TI - Emu oil decreases atherogenic plaque formation in cafeteria diet-induced obese
rats.
AB - BACKGROUND: Atherosclerosis-induced coronary heart disease - caused by elevated
levels of low-density lipoproteins (LDL) and inflammation - is one of the most
prevalent diseases. Monounsaturated fatty acids are reported to prevent
atherosclerosis; emu oil is a rich source of monounsaturated fatty acid, and we
hypothesize that emu oil supplementation could lower inflammation and prevent
atherosclerosis in diet-induced obese (DIO) animals. Male Wistar rats were
randomly divided into five groups (n = 6), and fed with normal diet (chow pellet;
ND), or with cafeteria diet (CD), or with CD along with emu oil supplementation
at three different doses: ED1 (2 mL), ED2 (4 mL) and ED3 (8 mL) kg(-1) body
weight (BW), respectively. RESULTS: After 12 weeks, the animals were sacrificed
and serum was analysed for measuring lipid profile, C-reactive proteins,
testosterone and luteinizing hormone. Histopathological studies were performed to
observe atherogenic changes in thoracic aorta. Restoration of altered lipid and
hormonal profiles, and inhibition of atherogenic changes in thoracic aorta, were
observed with supplementation of emu oil, confirming its anti-atherosclerotic
activity. CONCLUSION: The high content of oleic acid in emu oil could have
orchestrated - either solely or in combination with linoleic and linolenic acids
causing the upregulation of testosterone biosynthesis and inhibition of
atheromatous plaque formation in diet-induced obese animals. (c) 2015 Society of
Chemical Industry.
PMID- 26415676
TI - Next-generation-sequencing-based identification of familial hypercholesterolemia
related mutations in subjects with increased LDL-C levels in a latvian
population.
AB - BACKGROUND: Familial hypercholesterolemia (FH) is one of the commonest monogenic
disorders, predominantly inherited as an autosomal dominant trait. When
untreated, it results in early coronary heart disease. The vast majority of FH
remains undiagnosed in Latvia. The identification and early treatment of affected
individuals remain a challenge worldwide. Most cases of FH are caused by
mutations in one of four genes, APOB, LDLR, PCSK9, or LDLRAP1. The spectrum of
disease-causing variants is very diverse and the variation detection panels
usually used in its diagnosis cover only a minority of the disease-causing gene
variants. However, DNA-based tests may provide an FH diagnosis for FH patients
with no physical symptoms and with no known family history of the disease. Here,
we evaluate the use of targeted next-generation sequencing (NGS) to identify
cases of FH in a cohort of patients with coronary artery disease (CAD) and
individuals with abnormal low-density lipoprotein-cholesterol (LDL-C) levels.
METHODS: We used targeted amplification of the coding regions of LDLR, APOB,
PCSK9, and LDLRAP1, followed by NGS, in 42 CAD patients (LDL-C, 4.1-7.2 mmol/L)
and 50 individuals from a population-based cohort (LDL-C, 5.1-9.7 mmol/L).
RESULTS: In total, 22 synonymous and 31 nonsynonymous variants, eight variants in
close proximity (10 bp) to intron-exon boundaries, and 50 other variants were
found. We identified four pathogenic mutations (p.(Arg3527Gln) in APOB, and
p.(Gly20Arg), p.(Arg350*), and c.1706-10G > A in LDLR) in seven patients (7.6 %).
Three possible pathogenic variants were also found in four patients. CONCLUSION:
NGS-based methods can be used to detect FH in high-risk individuals when they do
not meet the defined clinical criteria.
PMID- 26415677
TI - Online technology use in physiotherapy teaching and learning: a systematic review
of effectiveness and users' perceptions.
AB - BACKGROUND: The use of online technologies in health professionals' education,
including physiotherapy, has been advocated as effective and well-accepted tools
for enhancing student learning. The aim of this study was to critically review
the effectiveness, and user perceptions of online technology for physiotherapy
teaching and learning. METHODS: Following databases were systematically searched
on the 31(st) of August 2013 for articles describing implementation of online
technologies into physiotherapy teaching and learning: ERIC, CINAHL, Web of
Science, Academic search complete, ProQuest Nursing and Allied Health Source,
Medline, Embase, and Scopus. No language, design or publishing date restrictions
were imposed. Risk of bias was assessed using the 2011 Mixed Methods Appraisal
Tool checklist (MMAT). RESULTS: A total of 4133 articles were retrieved; 22
articles met the inclusion criteria and were accepted for final analysis: 15 on
the effectiveness of technology, and 14 on users' perceptions. Included studies
used three designs: case study (14 articles), controlled trial (3), and
randomized controlled trial (5). Studies investigated both pre-registration
physiotherapy students (1523) and physiotherapy professionals (171). The quality
of studies ranged from 67 to 100 % on the MMAT checklist which can be considered
moderate to excellent. More than half of the studies (68 %) received scores
greater than 80 %. Studies typically investigated websites and discussion boards.
The websites are effective in enhancing practical skills performance, and
discussion boards in knowledge acquisition, as well as in development of critical
and reflective thinking. Students' perceptions of the use of websites were mostly
positive, providing students with entertaining, easy accessible resources.
Perceived barriers to the use of websites included difficulties with internet
connection, insufficiently interactive material, or personal preference for paper
based materials. Discussion boards were perceived as deepening students' thinking
and facilitating reflection, allowing for learning from multiple perspectives,
and providing easy communication and support. CONCLUSIONS: The results of this
review suggest that online technologies (i.e., websites and discussion boards)
have many benefits to offer for physiotherapy teaching and learning; There was
minimal evidence of barriers for the use of online technologies, however,
addressing the identified ones could enhance adherence to use of online
technologies in health professionals' education.
PMID- 26415678
TI - Angiotensin-converting enzyme inhibitor induced angioedema: predictors of
mechanical ventilation and treatment approaches.
PMID- 26415679
TI - Ventilatory support of patients with sepsis or septic shock in resource-limited
settings.
PMID- 26415680
TI - Predicting fluid responsiveness in 100 critically ill children: the effect of
baseline contractility.
AB - PURPOSE: Fluid overload is a risk factor for poor outcome in intensive care; thus
volume loading should be tailored towards patients who are likely to increase
stroke volume. We aimed to evaluate the paediatric predictive ability (stroke
volume increase of at least 15 % after fluid bolus) of novel and established
volumetric and dynamic haemodynamic variables, and assess the influence of
baseline contractility on response. METHODS: We assessed 142 volume loading
episodes (10 ml/kg crystalloid) in 100 critically ill ventilated children, median
(interquartile) weight 10 (5.6-15) kg. Eight advanced haemodynamic variables were
assessed using two commercially available devices. Systemic ventricular
contractility was measured as the maximum rate of systolic arterial pressure
rise. RESULTS: Overall, predictive ability was poor, with volumetric variables
performing better than dynamic (area under receiver operating characteristic
curves ranged from 0.53 to 0.67). The best predictor was total end-diastolic
volume index; however, this did not increase in a consistent way with volume
loading, with change post volume being weakly related to baseline values (r =
0.19, p = 0.02). A multivariable model quantified the importance of contractility
in stroke volume response. Children with high baseline contractility (>=75th
centile) typically achieved a positive stroke volume response when end-diastolic
volume values changed by 10-15 ml/m(2.6), whereas patients with low contractility
(<=25th centile) typically required end-diastolic volume increases of 35-40
ml/m(2.6). CONCLUSIONS: Current paediatric predictors of volume response perform
poorly; prediction may be improved if baseline contractility is taken into
account.
PMID- 26415681
TI - Understanding coma in bacterial meningitis.
PMID- 26415683
TI - Novel non-local effects in three-terminal hybrid devices with quantum dot.
AB - We predict non-local effect in the three-terminal hybrid device consisting of the
quantum dot (QD) tunnel coupled to two normal and one superconducting reservoirs.
It manifests itself as the negative non-local resistance and results from the
competition between the ballistic electron transfer (ET) and the crossed Andreev
scattering (CAR). The effect is robust both in the linear and non-linear regimes.
In the latter case the screening of charges and the long-range interactions play
significant role. We show that sign change of the non-local conductance depends
on the subgap Shiba/Andreev states, and it takes place even in absence of the
Coulomb interactions. The effect is large and can be experimentally verified
using the four probe setup. Since the induced non-local voltage changes sign and
magnitude upon varying the gate potential and/or coupling of the quantum dot to
the superconducting lead, such measurement could hence provide a controlled and
precise method to determine the positions of the Shiba/Andreev states. Our
predictions ought to be contrasted with non-local effects observed hitherto in
the three-terminal planar junctions where the residual negative non-local
conductance has been observed at large voltages, related to the Thouless energy
of quasiparticles tunneling through the superconducting slab.
PMID- 26415682
TI - Cytomegalovirus reactivation and mortality in patients with acute respiratory
distress syndrome.
AB - PURPOSE: Cytomegalovirus (CMV) reactivation occurs frequently in patients with
the acute respiratory distress syndrome (ARDS) and has been associated with
increased mortality. However, it remains unknown whether this association
represents an independent risk for poor outcome. We aimed to estimate the
attributable effect of CMV reactivation on mortality in immunocompetent ARDS
patients. METHODS: We prospectively studied immunocompetent ARDS patients who
tested seropositive for CMV and remained mechanically ventilated beyond day 4 in
two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads
were determined in plasma weekly. Competing risks Cox regression was used with
CMV reactivation status as a time-dependent exposure variable. Subsequently, in
sensitivity analyses we adjusted for the evolution of disease severity until
onset of reactivation using marginal structural modeling. RESULTS: Of 399 ARDS
patients, 271 (68%) were CMV seropositive and reactivation occurred in 74 (27%)
of them. After adjustment for confounding and competing risks, CMV reactivation
was associated with overall increased ICU mortality (adjusted subdistribution
hazard ratio (SHR) 2.74, 95% CI 1.51-4.97), which resulted from the joint action
of trends toward an increased mortality rate (direct effect; cause specific
hazard ratio (HR) 1.58, 95% CI 0.86-2.90) and a reduced successful weaning rate
(indirect effect; cause specific HR 0.83, 95% CI 0.58-1.18). These associations
remained in sensitivity analyses. The population-attributable fraction of ICU
mortality was 23% (95% CI 6-41) by day 30 (risk difference 4.4, 95% CI 1.1-7.9).
CONCLUSION: CMV reactivation is independently associated with increased case
fatality in immunocompetent ARDS patients who are CMV seropositive.
PMID- 26415684
TI - Unmet needs: relevance to medical technology innovation?
AB - This paper describes and discusses the role of unmet needs in the innovation of
new medical technologies using the National Institute for Health Research Devices
for Dignity (D4D) Healthcare Technology Co-operative as a case study. It defines
an unmet need, providing a spectrum of classification and discusses the benefits
and the challenges of identifying unmet need and its influence on the innovation
process. The process by which D4D has captured and utilized unmet needs to drive
technology innovation is discussed and examples given. It concludes by arguing
that, despite the challenges, defining and reviewing unmet need is a fundamental
factor in the success of medical technology innovation.
PMID- 26415685
TI - Unsaturated but not saturated fatty acids induce transcriptional regulation of
CCL2 in pancreatic acini. A potential role in acute pancreatitis.
PMID- 26415687
TI - Is there any substrate that is better than Ir(1 0 0) for diamond nucleation?
AB - The initial nucleation of adsorbed carbon (-C) and hydrocarbon groups (-CH,-C2H2,
CH2 and -CH3) on Ir, Pt, Au, Rh, and Co(1 0 0) surfaces are investigated for
diamond heteroepitaxial. It is revealed that the carbon-hydrogen ratios of the
adsorbed species play a key role: The relative stabilities of these species vary
while the coverage increases; at full coverage, only -C2H2 is favorable on the
surface. The Ir(1 0 0) surface is unique: it binds with the -C2H2 the most
strongly. The study not only answers why Ir(1 0 0) is by far the best substrate
for diamond heteroepitaxy, but also points out the searching direction for even
better substrate materials.
PMID- 26415688
TI - Antibiotic dose optimization in critically ill patients.
AB - The judicious use of existing antibiotics is essential for preserving their
activity against infections. In the era of multi-drug resistance, this is of
particular importance in clinical areas characterized by high antibiotic use,
such as the ICU. Antibiotic dose optimization in critically ill patients requires
sound knowledge not only of the altered physiology in serious infections -
including severe sepsis, septic shock and ventilator-associated pneumonia - but
also of the pathogen-drug exposure relationship (i.e.
pharmacokinetic/pharmacodynamic index). An important consideration is the fact
that extreme shifts in organ function, such as those seen in hyperdynamic
patients or those with multiple organ dysfunction syndrome, can have an impact
upon drug exposure, and constant vigilance is required when reviewing antibiotic
dosing regimens in the critically ill. The use of continuous renal replacement
therapy and extracorporeal membrane oxygenation remain important interventions in
these patients; however, both of these treatments can have a profound effect on
antibiotic exposure. We suggest placing emphasis on the use of therapeutic drug
monitoring and dose individualization when optimizing therapy in these settings.
PMID- 26415686
TI - Imaging disulfide dinitroxides at 250 MHz to monitor thiol redox status.
AB - Measurement of thiol-disulfide redox status is crucial for characterization of
tumor physiology. The electron paramagnetic resonance (EPR) spectra of disulfide
linked dinitroxides are readily distinguished from those of the corresponding
monoradicals that are formed by cleavage of the disulfide linkage by free thiols.
EPR spectra can thus be used to monitor the rate of cleavage and the thiol redox
status. EPR spectra of (1)H,(14)N- and (2)H,(15)N-disulfide dinitroxides and the
corresponding monoradicals resulting from cleavage by glutathione have been
characterized at 250 MHz, 1.04 GHz, and 9 GHz and imaged by rapid-scan EPR at 250
MHz.
PMID- 26415689
TI - Commonness, rarity, and intraspecific variation in traits and performance in
tropical tree seedlings.
AB - One of the few rules in ecology is that communities are composed of many rare and
few common species. Trait-based investigations of abundance distributions have
generally focused on species-mean trait values with mixed success. Here, using
large tropical tree seedling datasets in China and Puerto Rico, we take an
alternative approach that considers the magnitude of intraspecific variation in
traits and growth as it relates to species abundance. We find that common species
are less variable in their traits and growth. Common species also occupy core
positions within community trait space indicating that they are finely tuned for
the available conditions. Rare species are functionally peripheral and are likely
transients struggling for success in the given environment. The work highlights
the importance of considering intraspecific variation in trait-based ecology and
demonstrates asymmetry in the magnitude of intraspecific variation among species
is critical for understanding of how traits are related to abundance.
PMID- 26415690
TI - Cardiolipin metabolism and its causal role in the etiology of the inherited
cardiomyopathy Barth syndrome.
AB - Cardiolipin (CL) is a phospholipid with many unique characteristics. CL is
synthesized in the mitochondria and resides almost exclusively within the
mitochondrial inner membrane. Unlike most phospholipids that have two fatty acyl
chains, CL possesses four fatty acyl chains resulting in unique biophysical
characteristics that impact several biological processes including membrane
fission and fusion. In addition, several proteins directly bind CL including
proteins within the electron transport chain, the ADP/ATP carrier, and proteins
that mediate mitophagy. Tafazzin is an enzyme that remodels saturated fatty acyl
chains within CL to unsaturated fatty acyl chains, loss of function mutations in
the TAZ gene encoding tafazzin are causal for the inherited cardiomyopathy Barth
syndrome. Cells from Barth syndrome patients as well as several models of Barth
have reduced mitochondrial functions including impaired electron transport chain
function and increased reactive oxygen species (ROS) production. Mitochondria in
cells from Barth syndrome patients, as well as several model organism mimics of
Barth syndrome, are large and lack cristae consistent with the recently described
role of CL participating in the generation of mitochondrial membrane contact
sites. Cells with an inactive TAZ gene have also been shown to have a decreased
capacity to undergo mitophagy when faced with stresses such as increased ROS or
decreased mitochondrial quality control. This review describes CL metabolism and
how defects in CL metabolism cause Barth syndrome, the etiology of Barth
syndrome, and known modifiers of Barth syndrome phenotypes some of which could be
explored for their amelioration of Barth syndrome in higher organisms.
PMID- 26415692
TI - Suicide attempts in major depressive episode: evidence from the BRIDGE-II-Mix
study.
AB - OBJECTIVES: The Bipolar Disorders: Improving Diagnosis, Guidance, and Education
(BRIDGE-II-Mix) study aimed to estimate the frequency of mixed states in patients
with a major depressive episode (MDE) according to different definitions and to
compare their clinical validity, looking into specific features such as
suicidality. METHODS: A total of 2,811 subjects were enrolled in this multicenter
cross-sectional study. Psychiatric symptoms, and sociodemographic and clinical
variables were collected. The analysis compared the characteristics of patients
with MDE with (MDE-SA group) and without (MDE-NSA) a history of suicide attempts.
RESULTS: The history of suicide attempts was registered in 628 patients (22.34%).
In the MDE-SA group, women (72.5%, p = 0.028), (hypo)mania in first-degree
relatives (20.5%, p < 0.0001), psychotic features (15.1%, p < 0.0001), and
atypical features (9.2%, p = 0.009) were more prevalent. MDE-SA patients'
previous responses to treatment with antidepressants included more (hypo)manic
switches [odds ratio (OR) = 1.97, 95% confidence interval (CI): 1.58-2.44, p <
0.0001], treatment resistance (OR = 2.07, 95% CI: 1.72-2.49, p < 0.0001), mood
lability (OR = 1.98, 95% CI: 1.65-2.39, p < 0.0001), and irritability (OR = 1.80,
95% CI: 1.48-2.17, p < 0.0001). Multivariate analysis evidenced that risky
behavior, psychomotor agitation and impulsivity, and borderline personality and
substance use disorders were the variables most frequently associated with
previous suicide attempts. In the MDE-SA group, 75 patients (11.9%) fulfilled
Diagnostic and Statistical Manual (DSM)-5 criteria for MDE with mixed features,
and 250 patients (39.8%) fulfilled research-based diagnostic criteria for a mixed
depressive episode. CONCLUSIONS: Important differences between MDE-SA and MDE-NSA
patients have emerged. Early identification of symptoms such as risky behavior,
psychomotor agitation, and impulsivity in patients with MDE, and treatment of
mixed depressive states could represent a major step in suicide prevention.
PMID- 26415693
TI - Evaluation of mass drug administration in the program to control imported
lymphatic filariasis in Thailand.
AB - BACKGROUND: Migration plays a major role in the emergence and resurgence of
lymphatic filariasis (LF) in many countries. Because of the high prevalence of
Imported Bancroftian Filariasis (IBF) caused by nocturnally periodic Wuchereria
bancrofti and the intensive movement of immigrant workers from endemic areas,
Thailand has implemented two doses of 6 mg/kg diethylcarbamazine (DEC) with
interval of 6 months to prevent IBF. In areas where immigrants are very mobile,
the administration of DEC may be compromised. This study aimed to evaluate DEC
administration and its barriers in such areas. METHODS: A cross-sectional study
with two-stage stratified cluster sampling was conducted. We selected Myanmar
immigrants aged >18 years from factory and fishery areas of Samut Sakhon Province
for interview with a structured questionnaire. We also interviewed health
personnel regarding the functions of the LF program and practice of DEC delivery
among immigrants. Associations were measured by multiple logistic regression, at
P <0.05. RESULTS: DEC coverage among the immigrants was 75 %, below the national
target. All had received DEC only once during health examinations at general
hospitals for work permit renewals. None of the health centers in each community
provided DEC. Significant barriers to DEC access included being undocumented
(adjusted OR = 74.23; 95 % CI = 26.32-209.34), unemployed (adjusted OR = 5.09; 95
% CI = 3.39-7.64), daily employed (adjusted OR = 4.33; 95 % CI = 2.91-6.46),
short-term immigrant (adjusted OR = 1.62; 95 % CI = 1.04-2.52) and living in a
fishery area (adjusted OR = 1.57; 95 % CI = 1.04-2.52). Incorrect perceptions
about the side-effects of DEC also obstructed DEC access for Myanmar immigrants.
All positive LF antigenic immigrants reported visiting and emigrating from LF
endemic areas. CONCLUSION: Hospital-based DEC administration was an inappropriate
approach to DEC delivery in areas with highly mobile Myanmar immigrants.
Incorporating health-center personnel in DEC delivery twice yearly and improving
the perceptions of DEC side effects would likely increase DEC coverage among
Myanmar immigrants.
PMID- 26415691
TI - Antidiabetic treatment with gliptins: focus on cardiovascular effects and
outcomes.
AB - The traditional oral pharmacological therapy for type 2 diabetes mellitus (T2DM)
has been based on the prescription of metformin, a biguanide, as first line
antihyperglycemic agent world over. It has been demonstrated that after 3 years
of treatment, approximately 50% of diabetic patients could achieve acceptable
glucose levels with monotherapy; but by 9 years this had declined to only 25%.
Therefore, the implementation of a combined pharmacological therapy acting via
different pathways becomes necessary, and its combination with a compound of the
sulfonylurea group was along decades the most frequently employed prescription in
routine clinical practice. Meglitinides, glitazones and alpha-glucosidase
inhibitors were subsequently developed, but the five mentioned groups of oral
antihyperglycemic agents are associated with variable degrees of undesirable or
even severe cardiovascular events. The gliptins-also called dipeptidyl peptidase
4 (DPP4) inhibitors--are an additional group of antidiabetic compounds with
increasing clinical use. We review the status of the gliptins with emphasis on
their capabilities to positively or negatively affect the cardiovascular system,
and their potential involvement in major adverse cardiovascular events (MACE).
Alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin and
vildagliptin are the compounds currently in clinical use. Regardless differences
in chemical structure and metabolic pathways, gliptins as a group exert favorable
changes in experimental models. These changes, as an almost general rule, include
improved endothelial function, reduction of inflammatory markers, oxidative
stress ischemia/reperfusion injury and atherogenesis. In addition, increased
adiponectin levels and modest decreases in lipidemia and blood pressure were
reported. In clinical settings, several trials--notably the longer one, employing
sitagliptin, with a mean follow-up period of 3 years--did not show an increased
risk for ischemic events. Anyway, it should be emphasized that the encouraging
results from basic science were not yet translated into clinical evidence,
probably due the multiple and pleiotropic enzymatic effects of DPP4 inhibition.
Moreover, when employing saxagliptin, while the drug was not associated with an
augmented risk for ischemic events, it should be pinpointed that the rate of
hospitalization for heart failure was significantly increased. Gliptins as a
group constitute a widely accepted therapy for the management of T2DM, usually as
a second-line medication. Nonetheless, for the time being, a definite
relationship between gliptins treatment and improved cardiovascular outcomes
remains uncertain and needs yet to be proven.
PMID- 26415694
TI - The polymorphism rs763780 in the IL-17F gene is associated with response to
biological drugs in patients with psoriasis.
AB - Psoriasis improves when IL-17 is blocked. Anti-TNF drugs reduce the IL-17
signaling pathway, and anti-IL-17 drugs are being developed to treat moderate-to
severe psoriasis. We analyzed three SNPs in IL-17A (rs2275913 and rs10484879) and
IL-17F (rs763780) to look for an association with psoriasis and/or with response
to anti-TNF drugs or ustekinumab. We included 197 healthy controls and 194
patients with moderate-to-severe psoriasis. The results of the univariate
analysis showed an association between rs10484879 and psoriasis, although this
relationship disappeared after adjustment for HLA-C (rs12191877). We also found
an association between rs763780 (IL-17F) and response to ustekinumab (n = 70) and
infliximab (n = 37) at 3 and 6 months and an association between rs763780 and the
response to adalimumab at 6 months (n = 67).
PMID- 26415695
TI - Facilitated Fe Nutrition by Phenolic Compounds Excreted by the Arabidopsis
ABCG37/PDR9 Transporter Requires the IRT1/FRO2 High-Affinity Root Fe(2+)
Transport System.
PMID- 26415696
TI - A Pivotal Role of DELLAs in Regulating Multiple Hormone Signals.
AB - Plant phenotypic plasticity is controlled by diverse hormone pathways, which
integrate and convey information from multiple developmental and environmental
signals. Moreover, in plants many processes such as growth, development, and
defense are regulated in similar ways by multiple hormones. Among them,
gibberellins (GAs) are phytohormones with pleiotropic actions, regulating various
growth processes throughout the plant life cycle. Previous work has revealed
extensive interplay between GAs and other hormones, but the molecular mechanism
became apparent only recently. Molecular and physiological studies have
demonstrated that DELLA proteins, considered as master negative regulators of GA
signaling, integrate multiple hormone signaling pathways through physical
interactions with transcription factors or regulatory proteins from different
families. In this review, we summarize the latest progress in GA signaling and
its direct crosstalk with the main phytohormone signaling, emphasizing the
multifaceted role of DELLA proteins with key components of major hormone
signaling pathways.
PMID- 26415697
TI - Convenient preparation of deuterium-labeled analogs of peptides containing N
substituted glycines for a stable isotope dilution LC-MS quantitative analysis.
AB - N-substituted glycines constitute mimics of natural amino acids that are of great
interest in the peptide-based drug development. Peptoids-oligo(N-substituted
glycines) have been recently demonstrated to be highly active peptidomimetics in
biological systems, resistant to proteolytic degradation. We developed a method
of the deuterium labeling of peptidomimetics containing N-substituted glycine
residues via H/D exchange of their alpha-carbon hydrogen atoms. The labeling was
shown to be easy, inexpensive, and without the use of derivatization reagents or
the need for a further purification. The deuterons introduced at the alpha-carbon
atoms do not undergo a back exchange under acidic conditions during liquid
chromatography mass spectrometry (LC-MS) analysis. The LC-MS analysis of a
mixture of isotopologues revealed a co-elution of deuterated and nondeuterated
forms of the peptidomimetics, which may be useful in the quantitative isotope
dilution analysis of peptoids and other derivatives of N-substituted glycines.
PMID- 26415698
TI - Assessment of a panel of interleukin-8 reporter lung epithelial cell lines to
monitor the pro-inflammatory response following zinc oxide nanoparticle exposure
under different cell culture conditions.
AB - BACKGROUND: Stably transfected lung epithelial reporter cell lines pose an
advantageous alternative to replace complex experimental techniques to monitor
the pro-inflammatory response following nanoparticle (NP) exposure. Previously,
reporter cell lines have been used under submerged culture conditions, however,
their potential usefulness in combination with air-liquid interface (ALI)
exposures is currently unknown. Therefore, the aim of the present study was to
compare a panel of interleukin-8 promoter (pIL8)-reporter cell lines (i.e. green
or red fluorescent protein (GFP, RFP), and luciferase (Luc)), originating from
A549 lung epithelial type II-like cells cells, following NPs exposure under both
submerged and ALI conditions. METHODS: All cell lines were exposed to zinc oxide
(ZnO) NPs at 0.6 and 6.2 MUg/cm(2) for 3 and 16 hours under both submerged and
ALI conditions. Following physicochemical characterization, the cytotoxic profile
of the ZnO-NPs was determined for each exposure scenario. Expression of IL-8 from
all cell types was analyzed at the promoter level and compared to the mRNA (qRT
PCR) and protein level (ELISA). RESULTS: In summary, each reporter cell line
detected acute pro-inflammatory effects following ZnO exposure under each
condition tested. The pIL8-Luc cell line was the most sensitive in terms of
reporter signal strength and onset velocity following TNF-alpha treatment. Both
pIL8-GFP and pIL8-RFP also showed a marked signal induction in response to TNF
alpha, although only after 16 hrs. In terms of ZnO-NP-induced cytotoxicity pIL8
RFP cells were the most affected, whilst the pIL8-Luc were found the least
responsive. CONCLUSIONS: In conclusion, the use of fluorescence-based reporter
cell lines can provide a useful tool in screening the pro-inflammatory response
following NP exposure in both submerged and ALI cell cultures.
PMID- 26415700
TI - Raltegravir Plus Nevirapine as Maintenance Antiretroviral Therapy in HIV-Positive
Patients: Safety, Efficacy and Pharmacokinetics.
AB - BACKGROUND: Tolerability, long-term toxicities and selection of resistant
variants limit the use and efficacy of antiretroviral drugs in HIV-positive
patients. Novel combinations are needed for mantaining long-term control of HIV
replication; nevertheless scarse data are available on protease inhibitor-free
dual antiretroviral therapies. METHODS: A multi-centric retrospective study was
conducted including HIV-1-positive patients on raltegravir/nevirapine dual
regimens. Plasma concentrations were measured as therapeutic drug monitoring
while a subset of patients underwent intensive 12-hour pharmacokinetic
evaluation. RESULTS: A total of 77 patients switching from successful regimens
(76.6% male, median age 52 years) was included; 10 patients on raltegravir plus
nevirapine once-daily while 67 subjects on twice-daily schedule. After a median
follow-up of 32 months 69 patients (89.6%) were still successfully on treatment.
Three patients discontinued for side effects (skin rash or hepatoxicity).
Virological failure was observed in five patients (6.5%, 3 on once-daily
schedule): in 4 patients (80%) resistance-associated mutations were observed (4
reverse transcriptase, 2 integrase). Triglycerides decreased in patients
switching with lipid abnormalities (n=52) and estimated creatinine clearance
increased in those with less than 60 ml/min (n=13). Median trough raltegravir and
nevirapine concentrations were 83 ng/ml (32-227) and 5460 ng/ml (4037-7221);
intensive 12-hours pharmacokinetic parameters (n=7) were similar to published
data. CONCLUSION: Dual therapy with raltegravir/nevirapine in selected patients
was highly effective over a 32-month follow up: virological failure was
infrequent (6.5%), most common with once-daily schedule (60%) and often
associated with the selection of resistance-associated mutations (80%). Twice
daily raltegravir plus nevirapine deserves further clinical evaluation as an NRTI
and PI-sparing strategy in selected patients.
PMID- 26415699
TI - A resilient formin-derived cortical actin meshwork in the rear drives actomyosin
based motility in 2D confinement.
AB - Cell migration is driven by the establishment of disparity between the cortical
properties of the softer front and the more rigid rear allowing front extension
and actomyosin-based rear contraction. However, how the cortical actin meshwork
in the rear is generated remains elusive. Here we identify the mDia1-like formin
A (ForA) from Dictyostelium discoideum that generates a subset of filaments as
the basis of a resilient cortical actin sheath in the rear. Mechanical resistance
of this actin compartment is accomplished by actin crosslinkers and IQGAP-related
proteins, and is mandatory to withstand the increased contractile forces in
response to mechanical stress by impeding unproductive blebbing in the rear,
allowing efficient cell migration in two-dimensional-confined environments.
Consistently, ForA supresses the formation of lateral protrusions, rapidly
relocalizes to new prospective ends in repolarizing cells and is required for
cortical integrity. Finally, we show that ForA utilizes the phosphoinositide
gradients in polarized cells for subcellular targeting.
PMID- 26415701
TI - HIV-1 is spreading out of former high-risk population through heterosexual
transmission in Hebei, China.
AB - INTRODUCTION: Multiple specific populations, including MSMs, IDUs, and FPDs, are
involved in HIV epidemic in China. In the recent years, HIV transmission due to
heterosexual transmission also contributed greatly to HIV epidemic in China. Very
few studies have been fulfilled to characterize relationships of HIV-1 strains
prevalent in different populations. In this study, the phylogenetic relationships
of HIV-1 spreading in different populations were investigated. MATERIALS AND
METHODS: HIV-1 sero-positive patients infected through different routes were
enrolled into the study. Nested RT-PCR was used to amplify HIV gag and pol genes
followed by sequencing. RESULTS: Multiple subtypes, including subtype B (52.1%),
CRF01_AE (34.4%), CRF07_BC (6.3%), subtype C (4.2%), CRF02_AG (1.0%), CRF08_BC
(1.0%) and unique recombination forms (1.0%) were identified. Phylogenetic
analysis showed that strains from MSM, IDU, and FPDs grouped into clusters
separately. However, strains identified in heterosexual transmitted population
intermixed with all of other high risk populations. DISCUSSION AND CONCLUSION:
The genetic data supposed that HIV-1 was spreading out of MSMs, IDUs, and FPDs
through heterosexual transmission in Hebei, China. Urgent prevention and behavior
intervention in the population will be necessary. Furthermore, the detailed
sequence data will help the design of HIV-1 vaccines in China. Sequence Data: All
of sequences have been deposited into the GenBank with the accession number:
KJ820007-KJ820144.
PMID- 26415703
TI - Layer-by-layer assemblies for antibacterial applications.
AB - The adhesion and proliferation of bacteria on various artificial surfaces affects
the functionality of these specific interfaces. To overcome the problems caused
by bacterial growth on these surfaces, various antibacterial coatings were
developed. In this review, we summarized most of the antibacterial surfaces
prepared by the Layer-by-Layer (LbL) assembly approach and classified these LbL
films based on their antibacterial mechanisms. In the first group, the
bactericidal LbL assemblies which incorporate various biocides including heavy
metals, antibiotics, cationic molecules, antimicrobial peptides and enzymes are
able to kill surrounding or contacted bacteria. In the second group, we focused
on the physical aspects of film surfaces. Bacterial adhesion resistant LbL films
have been fabricated to adjust the substrate surface properties such as surface
free energy (or wettability), roughness, and surface charge which may affect the
adhesion of bacteria. Furthermore, as an enhancement in the antibacterial
efficiency, multifunctional LbL assemblies combining both bactericidal and
adhesion resistant functionalities were discussed. The advantages and limitations
of these antibacterial LbL assemblies were summarized and subsequently directions
for future development were proposed.
PMID- 26415702
TI - The modulation of carbonyl reductase 1 by polyphenols.
AB - Carbonyl reductase 1 (CBR1), an enzyme belonging to the short-chain
dehydrogenases/reductases family, has been detected in all human tissues. CBR1
catalyzes the reduction of many xenobiotics, including important drugs (e.g.
anthracyclines, nabumetone, bupropion, dolasetron) and harmful carbonyls and
quinones. Moreover, it participates in the metabolism of a number of endogenous
compounds and it may play a role in certain pathologies. Plant polyphenols are
not only present in many human food sources, but are also a component of many
popular dietary supplements and herbal medicines. Many studies reviewed herein
have demonstrated the potency of certain flavonoids, stilbenes and curcuminoids
in the inhibition of the activity of CBR1. Interactions of these polyphenols with
transcriptional factors, which regulate CBR1 expression, have also been reported
in several studies. As CBR1 plays an important role in drug metabolism as well as
in the protection of the organism against potentially harmful carbonyls, the
modulation of its expression/activity may have significant pharmacological and/or
toxicological consequences. Some polyphenols (e.g. luteolin, apigenin and
curcumin) have been shown to be very potent CBR1 inhibitors. The inhibition of
CBR1 seems useful regarding the increased efficacy of anthracycline therapy, but
it may cause the worse detoxification of reactive carbonyls. Nevertheless, all
known information about the interactions of polyphenols with CBR1 have only been
based on the results of in vitro studies. With respect to the high importance of
CBR1 and the frequent consumption of polyphenols, in vivo studies would be very
helpful for the evaluation of risks/benefits of polyphenol interactions with
CBR1.
PMID- 26415705
TI - Deworming and the immune status of HIV positive pre-antiretroviral therapy
individuals in Arba Minch, Chencha and Gidole hospitals, Southern Ethiopia.
AB - BACKGROUND: Helminths/HIV co-infections are very common in developing countries,
especially in Africa. The effect of overlapping distribution of HIV and helminths
becomes important because concomitant infection may exacerbate disease outcome of
HIV infection. The study aimed at determining the effect of deworming on the
immune status of helminth/HIV coinfected Pre-ART HIV patients attending three
health institutions in Southern Ethiopia. METHODS: 97 HIV-positive Pre-ART
individuals were observed into 2 groups on the basis of helminth co-infection and
no infection. Out of these, 66 study participants were helminths/HIV co-infected
and the remaining 31 study participants were helminths (-)/HIV (+) control.
Helminth/HIV co-infected participants CD4+ T-cell count was done at baseline,
after 15 weeks and 6 months after antihelminthics treatment. Data were analyzed
using SPSS version 16. RESULTS: Ascaris lumbricoides was the highest prevalent
soil transmitted helminths in Pre-ART individuals in this study. CD4+ T-cell
count in the Ascaris lumricoides/HIV co-infected was significantly higher (P =
0.05) and (P < 0.05) after 15 weeks and 6 months post-antihelminthics treatment
respectively. Also, after antihelminthic therapy, the CD4+ T-cell count
significantly increased (P < 0.005) in all treated helminth infections.
CONCLUSIONS: The study showed that treatment of ascariasis had a significant
effect on CD4+ T-cell count increase in the treated Pre-ART Ascaris
lumbricoides/HIV co-infected individuals; whereas the same positive effect was
not evident for other intestinal helminth parasites detected in the study. In
conclusion, this finding on Ascaris lumbricoides-specific nature of immune
interaction in helminth/HIV co-infection may partly explain the inconsistent
reports on the role of intestinal helminths on progression of HIV infection to
AIDS. Therefore, a well-designed longitudinal study on helminth species-specific
HIV/helminth co-infection will be needed to fully establish the possible benefits
of deworming in intestinal helminth/HIV co-infection.
PMID- 26415706
TI - Bronchial compression following pulmonary artery stenting in single ventricle
lesions: how to prevent, and how to decompress.
AB - OBJECTIVES: To assess airway compression during pulmonary artery (PA)
intervention in single ventricle (SV) palliation. BACKGROUND: SV lesions with a
prominent neo-aortic root are considered a high risk for branch PA and/or
bronchial stenosis. PA stenting is well established, but may result in
ipsilateral bronchial compression. METHODS: Single-centre retrospective analysis
of 19 palliated SV patients with branch PA stenosis and close proximity to the
ipsilateral main bronchus who underwent cardiac catheterisation at a median age
and weight of 8.5 years (0.5-25) and 16.5 kg (6-82) between 12/2011 and 05/2015.
RESULTS: Two of the 19 patients suffered an almost-closed left-main bronchus
(LMB) following PA stenting. Fortunately, LMB decompression succeeded in both
those patients by re-shaping the PA stents by compressing the chest while
splinting the LMB with an inflated balloon. To prevent the other 17 patients from
suffering this serious complication, we adopted a thorough preparation strategy:
13 patients underwent safe simultaneous bronchoscopy and cardiac catheterisation;
in the remaining 4 patients CT-angiography enabled accurate risk evaluation prior
to re-catheterisation. CONCLUSIONS: In SV lesions accompanied by branch PA
stenosis, thorough preparation via cross-sectional imaging is mandatory,
including simultaneous bronchoscopy and cardiac catheterisation in selected
cases, to rule out any airway compression before considering endovascular stent
implantation. If a PA stent's compression has already caused severe bronchial
obstruction, our balloon-splinted decompression technique should be considered.
PMID- 26415708
TI - Amphibian antimicrobial peptide fallaxin analogue FL9 affects virulence gene
expression and DNA replication in Staphylococcus aureus.
AB - The rapid rise in antibiotic-resistant pathogens is causing increased health
concerns, and consequently there is an urgent need for novel antimicrobial
agents. Antimicrobial peptides (AMPs), which have been isolated from a wide range
of organisms, represent a very promising class of novel antimicrobials. In the
present study, the analogue FL9, based on the amphibian AMP fallaxin, was studied
to elucidate its mode of action and antibacterial activity against the human
pathogen Staphylococcus aureus. Our data showed that FL9 may have a dual mode of
action against S. aureus. At concentrations around the MIC, FL9 bound DNA,
inhibited DNA synthesis and induced the SOS DNA damage response, whereas at
concentrations above the MIC the interaction between S. aureus and FL9 led to
membrane disruption. The antibacterial activity of the peptide was maintained
over a wide range of NaCl and MgCl(2) concentrations and at alkaline pH, while it
was compromised by acidic pH and exposure to serum. Furthermore, at subinhibitory
concentrations of FL9, S. aureus responded by increasing the expression of two
major virulence factor genes, namely the regulatory rnaIII and hla, encoding
alpha-haemolysin. In addition, the S. aureus-encoded natural tolerance mechanisms
included peptide cleavage and the addition of positive charge to the cell
surface, both of which minimized the antimicrobial activity of FL9. Our results
add new information about FL9 and its effect on S. aureus, which may aid in the
future development of analogues with improved therapeutic potential.
PMID- 26415707
TI - Matrix metalloproteinase-9-dependent mechanisms of reduced contractility and
increased stiffness in the aging heart.
AB - PURPOSE: Matrix metalloproteinases (MMPs) collectively degrade all extracellular
matrix (ECM) proteins. Of the MMPs, MMP-9 has the strongest link to the
development of cardiac dysfunction. Aging associates with increased MMP-9
expression in the left ventricle (LV) and reduced cardiac function. We
investigated the effect of MMP-9 deletion on the cardiac ECM in aged animals.
EXPERIMENTAL DESIGN: We used male and female middle-aged (10- to16-month old) and
old (20- to 24-month old) wild-type (WT) and MMP-9 null mice (n =
6/genotype/age). LVs were decellularized to remove highly abundant mitochondrial
proteins that could mask identification of relative lower abundant components,
analyzed by shotgun proteomics, and proteins of interest validated by immunoblot.
RESULTS: Elastin microfibril interface-located protein 1 (EMILIN-1) decreased
with age in WT (p < 0.05), but not in MMP-9 null. EMILIN-1 promotes integrin
dependent cell adhesion and EMILIN-1 deficiency has been associated with vascular
stiffening. Talin-2, a cytoskeletal protein, was elevated with age in WT (p <
0.05), and MMP-9 deficiency blunted this increase. Talin-2 is highly expressed in
adult cardiac myocytes, transduces mechanical force to the ECM, and is activated
by increases in substrate stiffness. Our results suggest that MMP-9 deletion may
reduce age-related myocardial stiffness, which may explain improved cardiac
function in MMP-9 null animals. CONCLUSIONS: We identified age-related changes in
the cardiac proteome that are MMP-9 dependent, suggesting MMP-9 as a possible
therapeutic target for the aging patient.
PMID- 26415709
TI - Changes in supraspinal and spinal excitability of the biceps brachii following
brief, non-fatiguing submaximal contractions of the elbow flexors in resistance
trained males.
AB - The purpose of the current study was to assess the effects of 5 brief (2s),
intermittent, submaximal elbow flexors voluntary contractions at 50% of maximal
voluntary contraction (MVC) on measures of central (i.e. supraspinal and spinal)
excitability. Supraspinal and spinal excitability of the biceps brachii were
assessed via transcranial magnetic stimulation (TMS) of the motor cortex and
transmastoid electrical stimulation (TMES) of the corticospinal tract,
respectively. TMS-induced motor-evoked potentials (MEPs), TMES-induced
cervicomedullary-evoked potentials (CMEPs), Erb's point peripheral nerve
stimulation and MVC were assessed prior to and following submaximal voluntary
contractions at 50% of MVC. The MEP to CMEP ratio increased (584+/-77.2%;
p=0.011) and CMEP amplitudes decreased (62+/-3.0%; p=0.02) immediately post
exercise. MVC force output did not change immediately post-exercise. The results
suggest that brief, non-fatiguing intermittent submaximal voluntary contractions
transiently enhance supraspinal excitability while decreasing spinal
excitability. The impact of these changes on one's ability to generate or
maintain force production remains unknown.
PMID- 26415710
TI - Porous poly (D,L-lactide-co-glycolide) acid/biosilicate(r) composite scaffolds
for bone tissue engineering.
AB - This study evaluated the effects of the Biosilicate(r) and poly (D,L-lactic-co
glycolic) acid composites on bone repair in a tibial bone defect model in rats by
means of using histological evaluation (histopathological and morphometric
analysis) and gene expression analysis. Eighty male Wistar rats (12 weeks old,
weighing +/-300 g) were randomly divided into two groups: Biosilicate(r) group
(BG) and Biosilicate(r) /PLGA group (BG/PLGA). Each group was euthanized at 3, 7,
14, and 21 days after surgery (n = 10 animals per time point). The main findings
showed that the incorporation of PLGA into BG had a significant effect on the
morphological structure of the material, accelerating mass loss, decreasing the
pH and increasing the calcium release. Furthermore, histologic analysis revealed
that the BG/PLGA showed increased material degradation, accompanied by higher
bone formation compared to BG, after 21 days of implantation. In addition, qRT
PCR analysis showed that BG/PLGA induced an upregulation of the osteogenic genes
related to BMP4, Runx2, ALP, and OC. These results show that the present BG/PLGA
composite may be used as a bone graft for inducing bone repair. (c) 2015 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 63-71, 2017.
PMID- 26415712
TI - Influence of selective digestion of elastin and collagen on mechanical properties
of human aortas.
AB - PURPOSE: There are two families of fibres taking part in the process of
mechanical loads transfer, i.e. elastin and collagen fibres. Their number,
spatial arrangement and specific properties determine the capacity of a blood
vessels to resist mechanical loads resulting from the impact of blood on vessel
walls. The purpose of the present paper is to define the load-bearing capacities
of elastin and collagen scaffolds equivalent to natural fibre arrangements of
human aorta and produced by selective digestion. METHODS: Samples of thoracic
human aortas were digested by using phosphate buffer of trypsin at pH 8.0 for 22
hours in order to degrade elastin and by autoclaving followed by incubation in
90% formic acid for 22 hours. The efficacy of digestion was assessed
immunohistochemically. Mechanical properties of pre-stretched native and digested
samples were determined by uniaxial tensile test. RESULTS: Samples subjected to
autoclaving have been successfully deprived of both types of collagen and elastin
has been intact. Treatment with trypsin caused a removal of elastin and the
presence of type I and IV collagen was demonstrated. Digestion of aortic samples
either by formic acid or trypsin has resulted significantly decreasing mechanical
properties in comparison with native samples. CONCLUSIONS: Collagen and elastin
scaffold-like stuctures have been effectively produced by selective digestion of
thoracic human aorta and their contribution to the load-bearing process was
evaluated. Isolated collagen network are more durable and stiffer and less
deformable than elastin network, hence are responsible for load-bearing process
at higher strain since the range of working of elastin is at lower strain values.
PMID- 26415711
TI - Physical Function and Disability After Acute Care and Critical Illness
Hospitalizations in a Prospective Cohort of Older Adults.
AB - OBJECTIVES: To investigate associations between acute care and critical illness
hospitalizations and performance on physical functional measures and activities
of daily living (ADLs). DESIGN: Prospective cohort study. SETTING: Large health
maintenance organization. PARTICIPANTS: Two thousand nine hundred twenty-six
participants in Adult Changes in Thought, a study of aging enrolling dementia
free individuals aged 65 and older not living in a nursing home from 1994 to
September 30, 2008 (N = 2,926). MEASUREMENTS: The exposure of interest was
hospitalization during study participation, subdivided by presence of critical
illness. Outcomes included gait speed, grip strength, chair stand speed, and
difficulty and dependence in performing ADLs measured at biennial visits.
RESULTS: Median time between hospital discharge and the next study visit was 311
days (interquartile range (IQR) 151-501 days) after acute care hospitalization
and 359 days (IQR 181-420 days) after critical illness hospitalization. Gait
speed was slower after acute care (-0.05 m/s, 95% confidence interval (CI) = 0.01
0.04 m/s slower, P < .001) and critical illness (-0.16 m/s, 95% CI = -0.22 to
0.10, P < .001). Grip was weaker after acute care hospitalization (-0.8 kg, 95%
CI = -1.0 to -0.6, P < .001) but not significantly different after critical
illness hospitalization. Chair-stand speed was slower after acute care
hospitalization (-0.04 stands/s, 95% CVI = -0.05 to -0.04, P < .001) and critical
illness hospitalization (-0.09, 95% CI = -0.15 to -0.03, P = .003). The odds of
difficulty with (odds ratio (OR) = 1.4, 95% CI = 1.2-1.6, P < .001) or dependence
in (OR = 2.0, 95% CI = 1.2-3.2, P = .006) one or more ADLs was higher after acute
care hospitalization, as were the odds of difficulty with (OR = 1.9, 95% CI = 1.1
3.6, P = .03) or dependence in (OR = 7.9, 95% CI = 2.5-25.7, P = .001) one or
more ADLs after critical illness. CONCLUSION: In older adults, hospitalization,
especially for critical illness, was associated with clinically relevant decline
in gait and chair stand speed and strongly associated with difficulty with and
dependence in ADLs.
PMID- 26415714
TI - Local Health Integration Networks: Build on their purpose.
AB - This article provides a high-level overview on the creation of Local Health
Integration Networks (LHINs) and illustrates the complexities involved in their
implementation. To understand regional structures such as LHINs, one must
understand the context in which design and execution takes place. The article
ends with a commentary on how Ontario is performing post-LHINs and discusses next
steps.
PMID- 26415713
TI - Implementation of an antenatal magnesium sulfate protocol for fetal
neuroprotection in preterm infants.
AB - The aim of our study was to assess the feasibility of implementing a protocol for
the use of magnesium sulfate to prevent cerebral palsy. This retrospective single
center study included all women with fetuses of gestational age <33 weeks of
gestation whose birth was planned or expected within 24 hours from September 2011
to December 2012. They were to receive magnesium sulfate, administered
intravenously as a 4-g bolus followed by a constant infusion of 1 g per hour. If
delivery had not occurred after 12 hours and was no longer considered imminent,
the infusion was to be discontinued. The study included 119 women, 81 (68.1%) of
whom received magnesium sulfate. Among the latter, 71 (87.5%) gave birth within
24 hours. The reasons treatment was not given were: omission by medical team
(19/38, 50%), urgent delivery (18/38, 47.4%), and contraindication to treatment
(1/38, 2.6%). The mean gestational age at protocol implementation was 29.6 +/-
2.1 weeks. Maternal monitoring, especially at the onset of infusion, appeared
suboptimal. No major maternal side effects were observed. Our study shows that
implementing a protocol for prevention of cerebral palsy by magnesium sulfate is
feasible in a tertiary obstetric center.
PMID- 26415715
TI - The First Nations Health Authority: A transformation in healthcare for BC First
Nations.
AB - More than 10 years of negotiation and a series of political agreements led to the
formation of a new First Nations health governance structure in British Columbia
and the beginning of new relationships in health between First Nations, federal,
and provincial governments. The First Nations Health Authority is the service
delivery arm of this structure and the first-of-its-kind for Canada. Equitable
and innovative health service and governance partnerships can bring decision
making closer to home and into the hands of First Nations communities and allows
using the best of western medicine combined with holistic and traditional
practices. Decolonizing old relationships and building new partnerships are
leading to greater alignment of culturally safe and effective health services
through coordination, integration, and shared decision-making in British
Columbia.
PMID- 26415716
TI - High speed, high temperature electrical characterization of phase change
materials: metastable phases, crystallization dynamics, and resistance drift.
AB - During the fast switching in Ge2Sb2Te5 phase change memory devices, both the
amorphous and fcc crystalline phases remain metastable beyond the fcc and
hexagonal transition temperatures respectively. In this work, the metastable
electrical properties together with crystallization times and resistance drift
behaviour of GST are studied using a high-speed, device-level characterization
technique in the temperature range of 300 K to 675 K.
PMID- 26415717
TI - Comment on "Curvature capillary migration of microspheres" by N. Sharifi-Mood, I.
B. Liu, K. J. Stebe, Soft Matter, 2015, 11, 6768.
AB - In a recent paper, Sharifi-Mood et al. studied colloidal particles trapped at a
liquid interface with opposite principal curvatures c1 = -c2. In the theory part,
they claim that the trapping energy vanishes at second order in Deltac = c1 - c2,
which would invalidate our previous result [Phys. Rev. E: Stat., Nonlinear, Soft
Matter Phys., 2006, 74, 041402]. Here we show that this claim arises from an
improper treatment of the outer boundary condition on the deformation field. For
both pinned and moving contact lines, we find that the outer boundary is
irrelevant, which confirms our previous work. More generally, we show that the
trapping energy is determined by the deformation close to the particle and does
not depend on the far-field.
PMID- 26415718
TI - Mechanical control of magnetism in oxygen deficient perovskite SrTiO3.
AB - Mechanical control of magnetism in perovskite oxides is an important and
promising approach in spintronics. Based on the first-principles calculations, we
demonstrate that a negative pressure leads to a great enhancement of magnetic
moment in deficient SrTiO3 with oxygen vacancies, whereas a positive pressure
results in the gradual disappearance of magnetism. Spin charge density, Bader
charge analysis and electronic density of states successfully elucidate the
origin and underlying physics of the enhancement and disappearance of magnetism.
It is found that the split electronic states of dz(2), dyz and dzx in the 3d
orbitals of Ti atoms remarkably contribute to the occupancy of majority spin
states under negative pressure, which induces a large magnetic moment. Under
positive pressure, however, the equal occupancy of both majority and minority t2g
and eg states leads to the disappearance of magnetization. In addition, both
negative and positive pressures can largely lower the vacancy formation enthalpy,
suggesting that the oxygen vacancy is preferable with pressure. Our findings may
provide a mechanism to achieve the pressure control of magnetization in
nonmagnetic perovskite oxides.
PMID- 26415719
TI - Fetal cardiovascular remodeling persists at 6 months in infants with intrauterine
growth restriction.
AB - OBJECTIVES: Intrauterine growth restriction is associated with increased
cardiovascular risk later in life but the link between fetal disease and
postnatal risk is not well-documented. We evaluated longitudinally the
association between cardiovascular remodeling in small-for-gestational-age (SGA)
fetuses and at 6 months of age. METHODS: A cohort of 80 SGA fetuses (defined by
estimated fetal and birth weights < 10(th) centile) delivered > 34 weeks'
gestation was compared with 80 normally grown age-matched control fetuses, with
follow-up at 6 months of corrected age (i.e. 6 months from estimated date of
delivery according to first-trimester crown-rump length). Cardiovascular
evaluation included a comprehensive echocardiographic assessment in both fetuses
and infants and blood pressure and aortic intima-media thickness (aIMT)
measurement in infants. Parameters were adjusted by linear regression analysis
for gender, gestational age at delivery, pre-eclampsia, prenatal glucocorticoid
exposure, Cesarean delivery, admission to neonatal intensive care unit and body
surface area. RESULTS: Both pre- and postnatally, when compared with controls,
the SGA group showed a more globular cardiac shape (left sphericity index:
controls 2.06 vs SGA 1.87 (P = 0.022) prenatally and 1.92 vs 1.67 (P = 0.007)
postnatally), as well as signs of systolic longitudinal dysfunction (systolic
annular peak velocity (S'): 7.2 vs 6.3 cm/s (P = 0.003) prenatally and 7.9 vs 6.4
cm/s (P < 0.001) postnatally; tricuspid annular plane systolic excursion: 7.2 vs
6.8 mm (P = 0.015) prenatally and 16.0 vs 14.2 mm (P < 0.001) postnatally) and
diastolic dysfunction (left isovolumetric relaxation time: 46 vs 52 ms (P <
0.001) prenatally and 50 vs 57 ms (P = 0.034) postnatally). In addition, infants
in the SGA group had increased mean blood pressure (mean: 61 vs 70 mmHg, P <
0.001) and maximum aIMT (0.57 vs 0.66 mm; P < 0.001). CONCLUSIONS: Primary
cardiovascular changes are already present in the SGA fetus and persist at 6
months of age. These data support prenatal cardiovascular remodeling as a
mechanistic pathway of increased risk later in life in cases of SGA, regardless
of Doppler abnormalities. Copyright (c) 2015 ISUOG. Published by John Wiley &
Sons Ltd.
PMID- 26415720
TI - Ablation of hippocampal neurogenesis in mice impairs the response to stress
during the dark cycle.
AB - The functional role of adult neurogenesis in the hippocampus remains the subject
of intense speculation. One recent hypothesis is that adult-born neurons
contribute to the endocrine and behavioural outputs of the stress response. Here
we show a genetic model system to ablate neurogenesis by inducibly deleting Tbr2
gene function specifically in the hippocampus and corroborate our findings in a
radiation-based model of neurogenesis deprivation. We found that mice with
ablation of new neurons in the dentate gyrus exhibit reduced anxiety during the
dark cycle. After restraint stress, corticosterone levels in neurogenesis
deficient mice decreased more quickly than controls and were more sensitive to
suppression by dexamethasone. Furthermore, glucocorticoid receptor target genes
and neuronal activity markers showed reduced expression after stress in
neurogenesis-deficient mice. These findings suggest that newborn neurons in the
hippocampus are involved in sensing and eliciting an appropriate response to
stress.
PMID- 26415721
TI - Traffic deaths before and after birth.
PMID- 26415722
TI - Cytoscape.js: a graph theory library for visualisation and analysis.
AB - Cytoscape.js is an open-source JavaScript-based graph library. Its most common
use case is as a visualization software component, so it can be used to render
interactive graphs in a web browser. It also can be used in a headless manner,
useful for graph operations on a server, such as Node.js. AVAILABILITY AND
IMPLEMENTATION: Cytoscape.js is implemented in JavaScript. Documentation,
downloads and source code are available at http://js.cytoscape.org. CONTACT:
gary.bader@utoronto.ca.
PMID- 26415725
TI - XPIWIT--an XML pipeline wrapper for the Insight Toolkit.
AB - The Insight Toolkit offers plenty of features for multidimensional image
analysis. Current implementations, however, often suffer either from a lack of
flexibility due to hard-coded C++ pipelines for a certain task or by slow
execution times, e.g. caused by inefficient implementations or multiple
read/write operations for separate filter execution. We present an XML-based
wrapper application for the Insight Toolkit that combines the performance of a
pure C++ implementation with an easy-to-use graphical setup of dynamic image
analysis pipelines. Created XML pipelines can be interpreted and executed by
XPIWIT in console mode either locally or on large clusters. We successfully
applied the software tool for the automated analysis of terabyte-scale, time
resolved 3D image data of zebrafish embryos. AVAILABILITY AND IMPLEMENTATION:
XPIWIT is implemented in C++ using the Insight Toolkit and the Qt SDK. It has
been successfully compiled and tested under Windows and Unix-based systems.
Software and documentation are distributed under Apache 2.0 license and are
publicly available for download at
https://bitbucket.org/jstegmaier/xpiwit/downloads/. CONTACT:
johannes.stegmaier@kit.edu SUPPLEMENTARY INFORMATION: Supplementary data are
available at Bioinformatics online.
PMID- 26415723
TI - ScreenBEAM: a novel meta-analysis algorithm for functional genomics screens via
Bayesian hierarchical modeling.
AB - MOTIVATION: Functional genomics (FG) screens, using RNAi or CRISPR technology,
have become a standard tool for systematic, genome-wide loss-of-function studies
for therapeutic target discovery. As in many large-scale assays, however, off
target effects, variable reagents' potency and experimental noise must be
accounted for appropriately control for false positives. Indeed, rigorous
statistical analysis of high-throughput FG screening data remains challenging,
particularly when integrative analyses are used to combine multiple sh/sgRNAs
targeting the same gene in the library. METHOD: We use large RNAi and CRISPR
repositories that are publicly available to evaluate a novel meta-analysis
approach for FG screens via Bayesian hierarchical modeling, Screening Bayesian
Evaluation and Analysis Method (ScreenBEAM). RESULTS: Results from our analysis
show that the proposed strategy, which seamlessly combines all available data,
robustly outperforms classical algorithms developed for microarray data sets as
well as recent approaches designed for next generation sequencing technologies.
Remarkably, the ScreenBEAM algorithm works well even when the quality of FG
screens is relatively low, which accounts for about 80-95% of the public
datasets. AVAILABILITY AND IMPLEMENTATION: R package and source code are
available at: https://github.com/jyyu/ScreenBEAM. CONTACT: ac2248@columbia.edu,
jose.silva@mssm.edu, yujiyang@gmail.com SUPPLEMENTARY INFORMATION: Supplementary
data are available at Bioinformatics online.
PMID- 26415724
TI - Drug-set enrichment analysis: a novel tool to investigate drug mode of action.
AB - MOTIVATION: Automated screening approaches are able to rapidly identify a set of
small molecules inducing a desired phenotype from large small-molecule libraries.
However, the resulting set of candidate molecules is usually very diverse
pharmacologically, thus little insight on the shared mechanism of action (MoA)
underlying their efficacy can be gained. RESULTS: We introduce a computational
method (Drug-Set Enrichment Analysis-DSEA) based on drug-induced gene expression
profiles, which is able to identify the molecular pathways that are targeted by
most of the drugs in the set. By diluting drug-specific effects unrelated to the
phenotype of interest, DSEA is able to highlight phenotype-specific pathways,
thus helping to formulate hypotheses on the MoA shared by the drugs in the set.
We validated the method by analysing five different drug-sets related to well
known pharmacological classes. We then applied DSEA to identify the MoA shared by
drugs known to be partially effective in rescuing mutant cystic fibrosis
transmembrane conductance regulator (CFTR) gene function in Cystic Fibrosis.
AVAILABILITY AND IMPLEMENTATION: The method is implemented as an online web tool
publicly available at http://dsea.tigem.it. CONTACT: dibernardo@tigem.it
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
online.
PMID- 26415726
TI - Computational probing protein-protein interactions targeting small molecules.
AB - MOTIVATION: With the booming of interactome studies, a lot of interactions can be
measured in a high throughput way and large scale datasets are available. It is
becoming apparent that many different types of interactions can be potential drug
targets. Compared with inhibition of a single protein, inhibition of protein
protein interaction (PPI) is promising to improve the specificity with fewer
adverse side-effects. Also it greatly broadens the drug target search space,
which makes the drug target discovery difficult. Computational methods are highly
desired to efficiently provide candidates for further experiments and hold the
promise to greatly accelerate the discovery of novel drug targets. RESULTS: Here,
we propose a machine learning method to predict PPI targets in a genomic-wide
scale. Specifically, we develop a computational method, named as PrePPItar, to
Predict PPIs as drug targets by uncovering the potential associations between
drugs and PPIs. First, we survey the databases and manually construct a gold
standard positive dataset for drug and PPI interactions. This effort leads to a
dataset with 227 associations among 63 PPIs and 113 FDA-approved drugs and allows
us to build models to learn the association rules from the data. Second, we
characterize drugs by profiling in chemical structure, drug ATC-code annotation,
and side-effect space and represent PPI similarity by a symmetrical S-kernel
based on protein amino acid sequence. Then the drugs and PPIs are correlated by
Kronecker product kernel. Finally, a support vector machine (SVM), is trained to
predict novel associations between drugs and PPIs. We validate our PrePPItar
method on the well-established gold-standard dataset by cross-validation. We find
that all chemical structure, drug ATC-code, and side-effect information are
predictive for PPI target. Moreover, we can increase the PPI target prediction
coverage by integrating multiple data sources. Follow-up database search and
pathway analysis indicate that our new predictions are worthy of future
experimental validation. CONCLUSION: In conclusion, PrePPItar can serve as a
useful tool for PPI target discovery and provides a general heterogeneous data
integrative framework. AVAILABILITY AND IMPLEMENTATION: PrePPItar is available at
http://doc.aporc.org/wiki/PrePPItar. CONTACT: ycwang@nwipb.cas.cn or
ywang@amss.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at
Bioinformatics online.
PMID- 26415727
TI - Association between self-reported snoring and arterial stiffness: data from the
Brisighella Heart Study.
AB - The correlation of both obstructive sleep apnoea syndrome (OSAS) and snoring with
cardiovascular risk is well known, but its investigation is complex and not
suitable for studying large cohorts of subjects. Thus, we prospectively evaluated
1476 non-pharmacologically treated subjects selected from the last survey of the
Brisighella Heart Study. Snoring and sleep apnoea were investigated asking the
subjects if they were aware of snoring during the night, and if this was
associated with episodes of apnoea. A full set of clinical and laboratory
parameters were evaluated, while augmentation index (AIx), and pulse wave
velocity (PWV) were recorded with the Vicorder((r)) apparatus. A logistic
regression analysis identifies as main independent predictors of AIx age (OR
1.058, 95% CI 1.043-1.065, p < 0.001), Body Mass Index (OR 1.046, 95% CI 1.014
1.079, p = 0.005), and apolipoprotein B (OR 1.014, 95% CI 1.004-1.023, p =
0.001). The main independent predictors of PWV are snoring (OR 1.215, 95% CI
1.083-1.390, p < 0.001), and snoring with apnoea (OR 1.351, 95% CI 1.135-1.598, p
= 0.014), age (OR 1.078, 95% CI 1.052-1.089, p < 0.001), serum uric acid [SUA]
(OR 1.093, 95% CI 1.026-1.151, p < 0.001) and mean arterial pressure (OR 1.042,
95% CI 1.024-1.056, p < 0.001). In conclusion, in our cohort of overall healthy
subjects, self-reported snoring and sleep apnoea are independently associated
with a higher PVW, and AIx is statistically significantly higher in snorers with
or without sleep apnoea than in non-snorers. Body Mass Index and apolipoprotein B
are associated with AIx, while SUA and mean arterial pressure are related to PWV.
PMID- 26415729
TI - Role of TBATB in nano indium oxide catalyzed C-S bond formation.
AB - Nano sized indium oxide is found to be an efficient catalyst for the conversion
of thiols to sulfides using Na2CO3 as base and TBATB as reagent in DMSO at 110
degrees C. Here in situ generation of bromo intermediate by TBATB takes place
through indium surface. A variety of aryl sulfides can be synthesized in
excellent yields from less reactive chlorides, boronic acids and thiols.
PMID- 26415728
TI - Neutrophil Gelatinase-Associated Lipocalin in Dogs With Sepsis Undergoing
Emergency Laparotomy: A Prospective Case-Control Study.
AB - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early
indicator of acute kidney injury (AKI) in dogs and its use has not been evaluated
in dogs with sepsis. ANIMALS: Fifteen dogs with sepsis requiring laparotomy
(study dogs) and 10 dogs undergoing surgery for intervertebral disc disease
(control dogs). OBJECTIVE: To determine whether NGAL increases in dogs with
sepsis undergoing emergency laparotomy and whether it is correlated with
development of AKI and survival. METHODS: Longitudinal study conducted at a
referral teaching hospital. Serum neutrophil gelatinase-associated lipocalin
(sNGAL), urinary NGAL normalized to urinary creatinine concentration (UNCR), and
serum creatinine concentration were measured at 4 time points (admission, after
anesthesia, and 24 and 48 hours postsurgery). Development of AKI (increase in
serum creatinine concentration of 0.3 mg/dL) and in-hospital mortality were
recorded. Linear mixed-model analysis was employed to assess differences between
groups over time. Mann-Whitney U-test was performed for comparison of continuous
variables between groups and Chi square or Fisher's exact tests were used to
assess correlation between discrete data. RESULTS: Serum NGAL and UNCR were
significantly higher in study dogs across all time points (P = .007 and P < .001,
respectively) compared with controls. Urinary NGAL normalized to creatinine in
the study group was not significantly different between survivors (n = 12) and
nonsurvivors (n = 3). Dogs that received hydroxyethyl starch had significantly
higher UNCR across all time points (P = .04) than those that did not. DISCUSSION
CONCLUSION: Serum neutrophil gelatinase-associated lipocalin and UNCR are
increased in dogs with sepsis requiring emergency laparotomy. Additional studies
are needed to evaluate its role as a marker of AKI in this population.
PMID- 26415730
TI - Abundance of specific mRNA transcripts impacts hatching success in European eel,
Anguilla anguilla L.
AB - Maternal mRNA governs early embryonic development in fish and variation in
abundance of maternal transcripts may contribute to variation in embryonic
survival and hatch success in European eel, Anguilla anguilla. Previous studies
have shown that quantities of the maternal gene products beta-tubulin, insulin
like growth factor 2 (igf2), nucleoplasmin (npm2), prohibitin 2 (phb2),
phosphatidylinositol glycan biosynthesis class F protein 5 (pigf5), and carnitine
O-palmitoyltransferase liver isoform-like 1 (cpt1) are associated with embryonic
developmental competence in other teleosts. Here, the relations between relative
mRNA abundance of these genes in eggs and/or embryos and egg quality, was studied
and analyzed. We compared egg quality of the two groups: i) batches with hatching
and ii) batches with no hatching. Results showed no significant differences in
relative mRNA abundance between the hatch and no hatching groups for any of the
selected genes at 0, 2.5, and 5HPF. However, at 30HPF the hatch group showed
significantly higher abundance of cpt1a, cpt1b, beta-tubulin, phb2, and pigf5
transcripts than the no hatch group. Therefore, these results indicate that up
regulation of the transcription of these genes in European eel after the mid
blastula transition, may be needed to sustain embryonic development and hatching
success.
PMID- 26415731
TI - Associations of arterial carbon dioxide and arterial oxygen concentrations with
hospital mortality after resuscitation from cardiac arrest.
AB - INTRODUCTION: Arterial concentrations of carbon dioxide (PaCO2) and oxygen (PaO2)
during admission to the intensive care unit (ICU) may substantially affect organ
perfusion and outcome after cardiac arrest. Our aim was to investigate the
independent and synergistic effects of both parameters on hospital mortality.
METHODS: This was a cohort study using data from mechanically ventilated cardiac
arrest patients in the Dutch National Intensive Care Evaluation (NICE) registry
between 2007 and 2012. PaCO2 and PaO2 levels from arterial blood gas analyses
corresponding to the worst oxygenation in the first 24 h of ICU stay were
retrieved for analyses. Logistic regression analyses were performed to assess the
relationship between hospital mortality and both categorized groups and a spline
based transformation of the continuous values of PaCO2 and PaO2. RESULTS: In
total, 5,258 cardiac arrest patients admitted to 82 ICUs in the Netherlands were
included. In the first 24 h of ICU admission, hypocapnia was encountered in 22 %,
and hypercapnia in 35 % of included cases. Hypoxia and hyperoxia were observed in
8 % and 3 % of the patients, respectively. Both PaCO2 and PaO2 had an independent
U-shaped relationship with hospital mortality and after adjustment for
confounders, hypocapnia and hypoxia were significant predictors of hospital
mortality: OR 1.37 (95 % CI 1.17-1.61) and OR 1.34 (95 % CI 1.08-1.66). A
synergistic effect of concurrent derangements of PaCO2 and PaO2 was not observed
(P = 0.75). CONCLUSIONS: The effects of aberrant arterial carbon dioxide and
arterial oxygen concentrations were independently but not synergistically
associated with hospital mortality after cardiac arrest.
PMID- 26415732
TI - MiR-140-3p suppressed cell growth and invasion by downregulating the expression
of ATP8A1 in non-small cell lung cancer.
AB - MicroRNAs (miRNAs) as a class of small noncoding RNA molecules regulate the
expression of targeted gene. The dysregulation of microRNAs is reported to be
involved in carcinogenesis and tumor progression. Here, we identified miR-140-3p
as a downregulated microRNA in most cancer tissues including lung cancer tissues,
compared with their normal counterparts. MiR-140-3p was observed to perform its
tumor suppressor function via its inhibition on cell growth, migration and
invasion but its induction of cell apoptosis. Furthermore, the growth of non
small-cell lung cancer (NSCLC) cells in nude mouse models were suppressed by
overexpression of miR-140-3p. ATP8A1 was demonstrated as a novel direct target of
miR-140-3p using a luciferase assay. The increased level of intracellular ATP8A1
protein attenuated the inhibitor role of miR-140-3p in the growth and mobility of
NSCLC cell. A regulation mechanism of miR-140-3p for the development and
progression of NSCLC through downregulating the ATP8A1 expression was first
discovered in the present study.
PMID- 26415733
TI - PI-88 inhibits postoperative recurrence of hepatocellular carcinoma via
disrupting the surge of heparanase after liver resection.
AB - Phosphomannopentaose sulfate (PI-88), an effective inhibitor of heparanase
(HPSE), exhibited anti-recurrence and anti-metastasis activity in preliminary
clinical trials of hepatocellular carcinoma (HCC); however, the underlying
mechanisms remain uncertain. Our aim was to reveal the mechanism by which PI-88
inhibits recurrence and intrahepatic metastasis. A tissue microarray containing
samples from 352 HCC patients was used to determine HPSE expression. We performed
enzyme-linked immunosorbent assay (ELISA) to detect plasma levels of HPSE in 40
HCC patients. We also used quantitative polymerase chain reaction, western blot
analysis, and immunohistochemical staining to assess HPSE expression of HCC cell
lines and tissues. The in vitro effects of PI-88 were examined by cell
proliferation and migration assays. In vivo PI-88 activity was assessed using
murine orthotopic HCC models. Intratumoral HPSE was an independent prognostic
marker for postsurgical overall survival (P = 0.001) and time to recurrence (P <
0.001) of HCC patients with hepatectomy. Elevated levels of HPSE were detected
both in postsurgical plasma of HCC patients and an orthotopic mouse model after
hepatectomy. PI-88 inhibited tumor recurrence and metastasis after liver
resection in the mouse model. In vitro expression of HPSE was up-regulated by
overexpression of early growth response 1 (EGR1), which is induced after
hepatectomy. Up-regulation of HPSE enhanced the sensitivity of HCC cells to PI-88
and the inhibitive effect of PI-88 on cell proliferation and migration. Our data
show that PI-88 effectively inhibits postoperative recurrence and intrahepatic
metastasis of HCC, providing an experimental basis for the clinical application
of PI-88 in HCC patients who have undergone hepatectomy.
PMID- 26415735
TI - Assisting the bereaved: A systematic review of the evidence for grief
counselling.
AB - BACKGROUND: Supporting people after bereavement is a priority area for many
health services. Investment in bereavement care must be supported by a rigorous
evidence-base. AIM: To examine the (1) relative proportion of descriptive,
measurement and intervention research in grief counselling and (2) quality and
effectiveness of intervention studies. DESIGN: Systematic review of studies
published in the area of grief counselling. DATA SOURCES: MEDLINE, Embase,
Cochrane Library and PsycINFO databases were searched for studies published
between 2000 and 2013. Eligible papers were categorised into descriptive,
measurement, review, commentaries and intervention studies. Intervention studies
were assessed against the Cochrane Effective Practice and Organisation of Care
methodological criteria, and papers meeting criteria were assessed for quality.
The impact of interventions on grief, psychological morbidity and quality of life
was examined. RESULTS: A total of 126 data-based papers, including 47
descriptive, 3 measurement and 76 grief counselling intervention studies were
included. Only 59% (n = 45) of intervention studies met Effective Practice and
Organisation of Care design criteria. Overall, study quality was poor, with the
majority of interventions showing a risk of bias in several key areas. The three
studies that met all criteria showed mixed effectiveness. CONCLUSION: Grief
counselling interventions require a strong rationale for design, and a systematic
approach to development and evaluation. Descriptive research efforts should
inform this process, focusing on homogeneity in sample, identification of risk
factors for complicated grief and the impact of extraneous factors on
intervention effects. Interventions should include comparisons to usual care, as
well as replication to confirm positive findings.
PMID- 26415736
TI - Discovering the hidden benefits of cognitive interviewing in two languages: The
first phase of a validation study of the Integrated Palliative care Outcome
Scale.
AB - BACKGROUND: The Integrated Palliative care Outcome Scale is a newly developed
advancement of the Palliative care Outcome Scale. It assesses patient-reported
symptoms and other concerns. Cognitive interviewing is recommended for
questionnaire refinement but not adopted widely in palliative care research. AIM:
To explore German- and English-speaking patients' views on the Integrated
Palliative care Outcome Scale with a focus on comprehensibility and
acceptability, and subsequently refine the questionnaire. METHODS: Bi-national
(United Kingdom/Germany) cognitive interview study using 'think aloud' and verbal
probing techniques. Interviews were audio-recorded, transcribed verbatim and
analysed using thematic analysis and pre-defined categories. Results from both
countries were collated and discussed. The Integrated Palliative care Outcome
Scale was then refined by consensus. SETTING/PARTICIPANTS: Purposely sampled
patients from four palliative care teams in palliative care units, general
hospital wards and in the community. RESULTS: A total of 15 German and 10 UK
interviews were conducted. Overall, comprehension and acceptability of the
Integrated Palliative care Outcome Scale were good. Identified difficulties
comprised the following: (1) comprehension problems with specific terms (e.g.
'mouth problems') and length of answer options; (2) judgement difficulties, for
example, due to the 3-day recall for questions; and (3) layout problems.
Combining the results from both countries (e.g. regarding 'felt good about
yourself') and discussing them from both languages' perspectives resulted in
wider consideration of the items' meaning, enabling more detailed refinement.
CONCLUSION: Cognitive interviewing proved valuable to increase face and content
validity of the questionnaire. The concurrent approach in two languages - to our
knowledge the first such approach in palliative care - benefited the refinement.
Psychometric validation of the refined Integrated Palliative care Outcome Scale
is now underway.
PMID- 26415734
TI - Comparison of meta-analyses among elastosonography (ES) and positron emission
tomography/computed tomography (PET/CT) imaging techniques in the application of
prostate cancer diagnosis.
AB - The early diagnosis of prostate cancer (PCa) appears to be of vital significance
for the provision of appropriate treatment programs. Even though several
sophisticated imaging techniques such as positron emission tomography/computed
tomography (PET/CT) and elastosonography (ES) have already been developed for PCa
diagnosis, the diagnostic accuracy of these imaging techniques is still
controversial to some extent. Therefore, a comprehensive meta-analysis in this
study was performed to compare the accuracy of various diagnostic imaging methods
for PCa, including 11C-choline PET/CT, 11C-acetate PET/CT, 18F-fluorocholine
PET/CT, 18F-fluoroglucose PET/CT, transrectal real-time elastosonography (TRTE),
and shear-wave elastosonography (SWE). The eligible studies were identified
through systematical searching for the literature in electronic databases
including PubMed, Cochrane, and Web of Science. On the basis of the fixed-effects
model, the pooled sensitivity (SEN), specificity (SPE), and area under the
receiver operating characteristics curve (AUC) were calculated to estimate the
diagnostic accuracy of 11C-choline PET/CT, 11C-acetate PET/CT, 18F-fluorocholine
(FCH) PET/CT, 18F-fluoroglucose (FDG) PET/CT, TRTE, and SWE. All the statistical
analyses were conducted with R language Software. The present meta-analysis
incorporating a total of 82 studies demonstrated that the pooled sensitivity of
the six imaging techniques were sorted as follows: SWE > 18F-FCH PET/CT > 11C
choline PET/CT > TRTE > 11C-acetate PET/CT > 18F-FDG PET/CT; the pooled
specificity were also compared: SWE > 18F-FCH PET/CT > 11C-choline PET/CT > TRTE
> 18F-FDG PET/CT > 11C-acetate PET/CT; finally, the pooled diagnostic accuracy of
the six imaging techniques based on AUC were ranked as below: SWE > 18F-FCH
PET/CT > 11C-choline PET/CT > TRTE > 11C-acetate PET/CT > 18F-FDG PET/CT. SWE and
18F-FCH PET/CT imaging could offer more assistance in the early diagnosis of PCa
than any other studied imaging techniques. However, the diagnostic ranking of the
six imaging techniques might not be applicable to the clinical phase due to the
shortage of stratified analysis.
PMID- 26415737
TI - The relevance of educating doctors, pharmacists and older patients about
potentially inappropriate medications.
AB - Providing appropriate pharmacotherapy to older people can be difficult since
older people are more at risk of developing adverse drug reactions due to age
related physiological changes. The use of potentially inappropriate medications
(PIMs) among older people is common throughout the globe, and is a cause for
concern due to their clinical, humanistic and economic implications.
Nevertheless, it appears that doctors and pharmacists have limited knowledge
regarding PIMs. Moreover, uninformed older patients may use PIMs without
considering their potential negative consequences. There is a need, therefore, to
educate doctors, pharmacists and older patients about PIMs. Geriatric
pharmacotherapy education with an emphasis on appropriate prescribing, and PIMs,
should be included in the medical and pharmacy teachings at the undergraduate,
postgraduate and continuing education levels. Moreover, older patients should be
informed about PIMs and the possible risks that they may pose.
PMID- 26415738
TI - Training on the use of a bespoke continuing professional development framework
improves the quality of CPD records.
AB - BACKGROUND: Using continuing professional development (CPD) as part of the
revalidation of pharmacy professionals has been proposed in the UK but not
implemented. We developed a CPD outcomes framework ('the framework') for scoring
CPD records, where the score range was -100 to +150 based on demonstrable
relevance and impact of the CPD on practice. OBJECTIVE: This exploratory study
aimed to test the outcome of training people to use the framework, through
distance-learning material (active intervention), by comparing CPD scores before
and after training. SETTING: Pharmacy professionals were recruited in the UK in
Reading, Banbury, Southampton, Kingston-upon-Thames and Guildford in 2009.
METHOD: We conducted a randomised, double-blinded, parallel-group, before and
after study. The control group simply received information on new CPD
requirements through the post; the active intervention group also received the
framework and associated training. Altogether 48 participants (25 control, 23
active) completed the study. All participants submitted CPD records to the
research team before and after receiving the posted resources. The records (n =
226) were scored blindly by the researchers using the framework. A subgroup of
CPD records (n = 96) submitted first (before-stage) and rewritten (after-stage)
were analysed separately. MAIN OUTCOME MEASURE: Scores for CPD records received
before and after distributing group-dependent material through the post. RESULTS:
Using a linear-regression model both analyses found an increase in CPD scores in
favour of the active intervention group. For the complete set of records, the
effect was a mean difference of 9.9 (95 % CI 0.4-19.3), p value = 0.04. For the
subgroup of rewritten records, the effect was a mean difference of 17.3 (95 % CI
5.6-28.9), p value = 0.0048. CONCLUSION: The intervention improved participants'
CPD behaviour. Training pharmacy professionals to use the framework resulted in
better CPD activities and CPD records, potentially helpful for revalidation of
pharmacy professionals.
PMID- 26415739
TI - Persistent expression and function of P-glycoprotein on peripheral blood
lymphocytes identifies corticosteroid resistance in patients with systemic lupus
erythematosus.
AB - Corticosteroids (CS) are the mainstay of treatment in systemic lupus
erythematosus (SLE) patients. However, some patients have poor response to CS
treatment. Among the multiple mechanisms of CS resistance, overexpression of P
glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as
this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp
protein on PBLs in patients with SLE in its response to CS therapy. SLE patients
(n = 42) (fulfilling ACR revised criteria) who were naive to CS and
immunosuppressive drugs were enrolled. Disease activity was assessed using SLE
disease activity index (SLEDAI) and expression, and function of P-gp was
evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At
3 months, patients with SLEDAI >4 and SLEDAI <=4 were grouped as nonresponders
and responders, respectively. P-gp expression was significantly increased on PBLs
of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and
function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001,
respectively). P-gp expression and function were not different in responders and
nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression
and function decreased in responders (p < 0.001 and p < 0.005, respectively),
whereas in nonresponders, it remained unchanged. Persistent overexpression and
activity of P-gp are associated with poor response to CS in CS naive patients of
SLE.
PMID- 26415740
TI - Prevalence of soluble peptidylarginine deiminase 4 (PAD4) and anti-PAD4
antibodies in autoimmune diseases.
AB - The objectives of this study are to investigate the prevalence of PAD4 and anti
PAD4 antibodies (Abs) in autoimmune diseases and to clarify their association
with anticitrullinated protein antibodies (ACPAs) and shared epitope (SE) in
patients with rheumatoid arthritis (RA). Levels of human PAD4 and anti-PAD4 Abs
in serum or plasma were measured using sandwich ELISA. Samples were obtained from
patients with RA (n = 148), SLE (n = 36), or SS (n = 37) and from healthy
controls (HCs; n = 40). Antibodies against cyclic citrullinated glucose-6
phosphate isomerase (GPI) (CCG)-2, CCG-7, anti-CEP-1, and anti-CCP Abs were also
measured using ELISA. Patients with RA were genotyped for HLA-DRB1. The human
PAD4 and anti-PAD4 Ab levels were compared with the ACPA and SE in patients with
RA. The PAD4 levels were 111.9 U/ml in the RA, 30.4 U/ml in the SLE, 81.9 U/ml in
the SS patients, and 46.6 U/ml in the HCs. The PAD4 levels were significantly
higher in the RA than in the SLE patients or the HCs. Anti-PAD4 Abs were detected
in 29.7 % of the patients with RA, but not in the patients with SLE or SS, nor in
the HCs. In the RA patients, the PAD4 levels in the anti-PAD4 Ab-negative group
were significantly higher than those in the anti-PAD4 Ab-positive group.
Moreover, anti-CCG-2, CCG-7, CEP-1, and anti-CCP Ab levels were significantly
higher in the anti-PAD4 Ab-positive group than in the anti-PAD4 Ab-negative
group. In the RA patients, the PAD4 levels were not correlated with ACPAs.
Neither PAD4 nor anti-PAD4 Abs were significantly correlated with the presence of
SE alleles. The PAD4 levels were higher in RA than in SLE or HC. Anti-PAD4 Abs
appeared specifically in patients with RA. Moreover, anti-PAD4 Abs were
associated with ACPAs.
PMID- 26415742
TI - Variational methods for fitting complex Bayesian mixed effects models to health
data.
AB - We consider approximate inference methods for Bayesian inference to longitudinal
and multilevel data within the context of health science studies. The complexity
of these grouped data often necessitates the use of sophisticated statistical
models. However, the large size of these data can pose significant challenges for
model fitting in terms of computational speed and memory storage. Our methodology
is motivated by a study that examines trends in cesarean section rates in the
largest state of Australia, New South Wales, between 1994 and 2010. We propose a
group-specific curve model that encapsulates the complex nonlinear features of
the overall and hospital-specific trends in cesarean section rates while taking
into account hospital variability over time. We use penalized spline-based smooth
functions that represent trends and implement a fully mean field variational
Bayes approach to model fitting. Our mean field variational Bayes algorithms
allow a fast (up to the order of thousands) and streamlined analytical
approximate inference for complex mixed effects models, with minor degradation in
accuracy compared with the standard Markov chain Monte Carlo methods.
PMID- 26415741
TI - Feeding butter with elevated content of trans-10, cis-12 conjugated linoleic acid
to obese-prone rats impairs glucose and insulin tolerance.
AB - BACKGROUND: We recently demonstrated that feeding a natural CLAt10,c12-enriched
butter to lean female rats resulted in small, but significant increases in
fasting glucose and insulin concentrations, and impaired insulin tolerance. Our
goal was to extend these findings by utilizing the diabetes-prone female fatty
Zucker rat. Rats were fed custom diets containing 45 % kcal of fat derived from
control and CLAt10,c12-enriched butter for 8 weeks. METHODS: CLA t10,c12-enriched
butter was prepared from milk collected from cows fed a high fermentable
carbohydrate diet to create subacute rumen acidosis (SARA); control (non-SARA)
butter was collected from cows fed a low grain diet. Female fatty Zucker rats (10
weeks old) were randomly assigned to one of four diet treatments: i) low fat (10
% kcal), ii) 45 % kcal lard, iii) 45 % kcal SARA butter, or iv) 45 % kcal non
SARA butter. A low fat fed lean Zucker group was used as a control group. After 8
weeks, i) glucose and insulin tolerance tests, ii) insulin signaling in muscle,
adipose and liver, and iii) metabolic caging measurements were performed.
RESULTS: Glucose and insulin tolerance were significantly impaired in all fatty
Zucker groups, but to the greatest extent in the LARD and SARA conditions.
Insulin signaling (AKT phosphorylation) was impaired in muscle, visceral
(perigonadal) adipose tissue and liver in fatty Zucker rats, but was generally
similar across dietary groups. Physical activity, oxygen consumption, food intake
and weight gain were also similar amongst the various fatty Zucker groups.
CONCLUSIONS: Increasing the consumption of a food naturally enriched with
CLAt10,c12 significantly worsens glucose and insulin tolerance in a diabetes
prone rodent model. This outcome is not explained by changes in tissue insulin
signaling, physical activity, energy expenditure, food intake or body mass.
PMID- 26415743
TI - [Impact of pharmaceutical intervention in preventing relapses in depression in
Primary Care].
AB - OBJECTIVE: To evaluate the long-term impact of a brief pharmacist intervention
(PI) compared with usual care (UC) on prevention of depression relapse. DESIGN:
randomised controlled clinical trial SETTING: Primary Care PARTICIPANTS: Of the
179 depressed patients initiating antidepressants, the 113 whose clinical
symptoms had remitted (main definition) at 6 months assessment were selected for
this secondary study (PI=58; UC=55). INTERVENTION: PI was an interview to promote
medication adherence when patients get antidepressants from pharmacy. MAIN
MEASUREMENTS: Baseline, 3 months, and six-months follow-up assessments were made.
The severity of depressive symptoms was evaluated with PHQ9. Patients presenting
a remission of symptoms were selected. The patient medical records were reviewed
to identify a relapse in the following 12 months by using 4 indicators. RESULTS:
There was a lower proportion of patients that relapsed in the PI group than in
the UC group 18 months after initiation of treatment, but the difference was not
statistically significant either in the intent-to-treat analysis (OR=0.734
[95%CI; 0.273-1.975]) or the per-protocol analysis (OR=0.615 [95%CI; 0.183
2.060]). All the sensitivity analyses showed consistent results. The sample size
and adherence to the protocol in the intervention group were low. CONCLUSION: PI
group showed a non-statistically significant tendency towards presenting fewer
relapses. This could be related to the improvement in adherence among patients
that received the intervention.
PMID- 26415744
TI - Mapping viscoelastic properties of healthy and pathological red blood cells at
the nanoscale level.
AB - In order to pass through the microcirculation, red blood cells (RBCs) need to
undergo extensive deformations and to recover the original shape. This extreme
deformability is altered by various pathological conditions. On the other hand,
an altered RBC deformability can have major effects on blood flow and can lead to
pathological implications. The study of the viscoelastic response of red blood
cells to mechanical stimuli is crucial to fully understand deformability changes
under pathological conditions. However, the typical erythrocyte biconcave shape
hints to a complex and intrinsically heterogeneous mechanical response that must
be investigated by using probes at the nanoscale level. In this work, the local
viscoelastic behaviour of healthy and pathological red blood cells was probed by
Atomic Force Microscopy (AFM). Our results clearly show that the RBC stiffness is
not spatially homogeneous, suggesting a strong correlation with the erythrocyte
biconcave shape. Moreover, our nanoscale mapping highlights the key role played
by viscous forces, demonstrating that RBCs do not behave as pure elastic bodies.
The fundamental role played by viscous forces is further strengthened by the
comparison between healthy and pathological (diabetes mellitus) RBCs. It is well
known that pathological RBCs are usually stiffer than the healthy ones. Our
measures unveil a more complex scenario according to which the difference between
normal and pathological red blood cells does not merely lie in their stiffness
but also in a different dynamical response to external stimuli that is governed
by viscous forces.
PMID- 26415745
TI - Cumulative Attributable Difference: An Infection Metric That Reflects a Value
System.
PMID- 26415746
TI - Understanding barriers to home-based and self-care in-center hemodialysis.
AB - Despite superior outcomes and lower associated costs, relatively few patients
with end-stage renal disease undergo self-care or home hemodialysis. Few studies
have examined patient- and physician-specific barriers to self-care and home
hemodialysis in the modern era. The degree to which innovative technology might
facilitate the adoption of these modalities is unknown. We surveyed 250 patients
receiving in-center hemodialysis and 51 board-certified nephrologists to identify
key barriers to adoption of self-care and home hemodialysis. Overall, 172 (69%)
patients reported that they were "likely" or "very likely" to consider self-care
hemodialysis if they were properly trained on a new hemodialysis system designed
for self-care or home use. Nephrologists believed that patients were capable of
performing many dialysis-relevant tasks, including: weighing themselves (98%),
wiping down the chair and machine (84%), clearing alarms during treatment (53%),
taking vital signs (46%), and cannulating vascular access (41%), but thought that
patients would be willing to do the same in only 69%, 34%, 31%, 29%, and 16%,
respectively. Reasons that nephrologists believe patients are hesitant to pursue
self-care or home hemodialysis do not correspond in parallel or by priority to
reasons reported by patients. Self-care and home hemodialysis offer several
advantages to patients and dialysis providers. Overcoming real and perceived
barriers with new technology, education and coordinated care will be required for
these modalities to gain traction in the coming years.
PMID- 26415747
TI - Phosphorylation of alphaB-crystallin: Role in stress, aging and patho
physiological conditions.
AB - BACKGROUND: alphaB-crystallin, once thought to be a lenticular protein, is
ubiquitous and has critical roles in several cellular processes that are
modulated by phosphorylation. Serine residues 19, 45 and 59 of alphaB-crystallin
undergo phosphorylation. Phosphorylation of S45 is mediated by p44/42 MAP kinase,
whereas S59 phosphorylation is mediated by MAPKAP kinase-2. Pathway involved in
S19 phosphorylation is not known. SCOPE OF REVIEW: The review highlights the role
of phosphorylation in (i) oligomeric structure, stability and chaperone activity,
(ii) cellular processes such as apoptosis, myogenic differentiation, cell cycle
regulation and angiogenesis, and (iii) aging, stress, cardiomyopathy-causing
alphaB-crystallin mutants, and in other diseases. MAJOR CONCLUSIONS: Depending on
the context and extent of phosphorylation, alphaB-crystallin seems to confer
beneficial or deleterious effects. Phosphorylation alters structure, stability,
size distribution and dynamics of the oligomeric assembly, thus modulating
chaperone activity and various cellular processes. Phosphorylated alphaB
crystallin has a tendency to partition to the cytoskeleton and hence to the
insoluble fraction. Low levels of phosphorylation appear to be protective, while
hyperphosphorylation has negative implications. Mutations in alphaB-crystallin,
such as R120G, Q151X and 464delCT, associated with inherited myofibrillar
myopathy lead to hyperphosphorylation and intracellular inclusions. An ongoing
study in our laboratory with phosphorylation-mimicking mutants indicates that
phosphorylation of R120GalphaB-crystallin increases its propensity to aggregate.
GENERAL SIGNIFICANCE: Phosphorylation of alphaB-crystallin has dual role that
manifests either beneficial or deleterious consequences depending on the extent
of phosphorylation and interaction with cytoskeleton. Considering that disease
causing mutants of alphaB-crystallin are hyperphosphorylated, moderation of
phosphorylation may be a useful strategy in disease management. This article is
part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
PMID- 26415748
TI - The body fades away: investigating the effects of transparency of an embodied
virtual body on pain threshold and body ownership.
AB - The feeling of "ownership" over an external dummy/virtual body (or body part) has
been proven to have both physiological and behavioural consequences. For
instance, the vision of an "embodied" dummy or virtual body can modulate pain
perception. However, the impact of partial or total invisibility of the body on
physiology and behaviour has been hardly explored since it presents obvious
difficulties in the real world. In this study we explored how body transparency
affects both body ownership and pain threshold. By means of virtual reality, we
presented healthy participants with a virtual co-located body with four different
levels of transparency, while participants were tested for pain threshold by
increasing ramps of heat stimulation. We found that the strength of the body
ownership illusion decreases when the body gets more transparent. Nevertheless,
in the conditions where the body was semi-transparent, higher levels of ownership
over a see-through body resulted in an increased pain sensitivity. Virtual body
ownership can be used for the development of pain management interventions.
However, we demonstrate that providing invisibility of the body does not increase
pain threshold. Therefore, body transparency is not a good strategy to decrease
pain in clinical contexts, yet this remains to be tested.
PMID- 26415749
TI - Attachment Style and Less Severe Forms of Sexual Coercion: A Systematic Review.
AB - Few studies have examined how attachment insecurity (i.e., attachment anxiety,
attachment avoidance) is associated with the more subtle and less severe forms of
sexual coercion, such as verbal threats and partner manipulation. This is despite
the fact that past research has indicated some of the relationship behaviors
exhibited by insecurely attached individuals represent behaviors indicative of
either the perpetration or victimization of less severe forms of sexual coercion.
The aim of this study was to conduct a systematic review on the association
between attachment style and less severe forms of sexual coercion. Our search,
which included published journal papers, book chapters, and theses published
between January 1970 and October 2014, yielded 1091 records. Examination of these
records against exclusion criteria yielded 11 studies that focused on the
associations between attachment orientation and perpetration of sexual coercion
(n = 3), sexual coercion victimization (n = 3), or both perpetration and
victimization (n = 5). Findings revealed that attachment anxiety appeared to be
more consistently associated with being the victim of sexual coercion than
attachment avoidance. In terms of perpetration, attachment avoidance was more
consistently associated with sexual coercion. These findings were observed when
examining the association between attachment dimensions and motives for sexual
coercion. The findings also revealed gender to be a moderator for victimization.
This review provides insights into how attachment style may influence the
perpetration and victimization of sexual coercion.
PMID- 26415750
TI - Evaluation of a dilution method for non-evaluable results in the detection of
Chlamydia trachomatis and Neisseria gonorrhoeae with the Cobas 4800 platform.
AB - INTRODUCTION: A variable percentage of samples analysed using the Cobas 4800
assay can give an invalid result by PCR inhibition or erroneous due to incorrect
DNA extraction with the Cobas 4800 CT/NG test. METHOD: An analysis was performed
using the vortex agitation and dilution protocol on the original sample (swab or
urine) for a total of 116 samples. In order to analyse the sensitivity of this
method, 100 samples (swabs and urine) with known results were retested. RESULTS:
A total of 98.3% (114/116) of the samples analysed were resolved with this
protocol with 100% agreement after reviewing clinical data, Gram stain, and other
samples analysed in parallel from the same patient. DISCUSSION: The data indicate
no loss of sensitivity with this protocol; thus Cobas 4800 users could use this
method without the need for alternative methods.
PMID- 26415751
TI - A systematic review of reliable and valid tools for the measurement of patient
participation in healthcare.
AB - INTRODUCTION: Patient participation in healthcare is recognised internationally
as essential for consumer-centric, high-quality healthcare delivery. Its
measurement as part of continuous quality improvement requires development of
agreed standards and measurable indicators. AIM: This systematic review sought to
identify strategies to measure patient participation in healthcare and to report
their reliability and validity. In the context of this review, patient
participation was constructed as shared decision-making, acknowledging the
patient as having critical knowledge regarding their own health and care needs
and promoting self-care/autonomy. METHODS: Following a comprehensive search,
studies reporting reliability or validity of an instrument used in a healthcare
setting to measure patient participation, published in English between January
2004 and March 2014 were eligible for inclusion. RESULTS: From an initial search,
which identified 1582 studies, 156 studies were retrieved and screened against
inclusion criteria. Thirty-three studies reporting 24 patient participation
measurement tools met inclusion criteria, and were critically appraised. The
majority of studies were descriptive psychometric studies using prospective,
cross-sectional designs. Almost all the tools completed by patients, family
caregivers, observers or more than one stakeholder focused on aspects of patient
professional communication. Few tools designed for completion by patients or
family caregivers provided valid and reliable measures of patient participation.
There was low correlation between many of the tools and other measures of patient
satisfaction. CONCLUSION: Few reliable and valid tools for measurement of patient
participation in healthcare have been recently developed. Of those reported in
this review, the dyadic Observing Patient Involvement in Decision Making (dyadic
OPTION) tool presents the most promise for measuring core components of patient
participation. There remains a need for further study into valid, reliable and
feasible strategies for measuring patient participation as part of continuous
quality improvement.
PMID- 26415752
TI - Response of human bone marrow-derived MSCs on triphasic Ca-P substrate with
various HA/TCP ratio.
AB - Calcium phosphates (Ca-P) are used commonly as artificial bone substitutes to
control the biodegradation rate of an implant in the body fluid. This study
examined the in vitro proliferation of human bone marrow-derived mesenchymal stem
cells (hBMSCs) on triphasic Ca-P samples. For this aspect, hydroxyapatite (HA),
dicalcium phosphate dehydrate (DCPD), and calcium hydroxide (Ca(OH)2 ) were mixed
at various ratios, cold compacted, and sintered at 1250 degrees C in air. X-ray
diffraction showed that the beta-tricalcium phosphate (TCP) to alpha-TCP phase
transformation increased with increasing DCPD/HA ratio. The micro-hardness
deceased with increasing TCP content, whereas the mean grain size and porosity
increased with increasing TCP concentration. To evaluate the in vitro degree of
adhesion and proliferation on the HA/TCP samples, human BMSCs were incubated on
the HA/TCP samples and analyzed by a cells proliferation assay, expression of the
extracellular matrix (ECM) genes, such as alpha-smooth muscle actin (alpha-SMA)
and fibronectin (FN), and FITC-phalloidin fluorescent staining. In terms of the
interactions of human BMSCs with the triphasic Ca-P samples, H50T50 (Ca/P = 1.59)
markedly enhanced cell spreading, proliferation, FN, and alpha-SMA compared with
H100T0 (Ca/P = 1.67). Interestingly, these results show that among the five
HA/TCP samples, H50T50 is the optimal Ca-P composition for in vitro cell
proliferation. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
Biomater, 105B: 72-80, 2017.
PMID- 26415753
TI - Complete genome sequencing of a genotype 3 hepatitis E virus strain identified in
a swine farm in Italy.
AB - In this study, we investigated hepatitis E virus (HEV) infection in piglets
sampled in two farms in southern Italy. The virus was detected in 11 out of 15
animals tested. Based on sequence analysis, the 6 Italian strains examined
belonged to two clusters containing both swine and human strains of either
genotype 3 subtype e or f from Europe and Japan. The two Italian strain clusters
shared nucleotide identity of 81.8% and 87.5% in the ORF2 (capsid protein) and
ORF1 (RdRp) diagnostic fragments, respectively, confirming the heterogeneity of
genotype 3 viruses circulating in pigs in Italy. The complete genome of one
genotype 3 subtype e strain and the full ORF2 and ORF3 coding regions of one of
the genotype 3f strains, obtained in this study, were compared to other HEV
sequences available on line (NCBI database). The results of analysis showed that
porcine strains clustered together with human and swine strains detected in
Europe. Most changes in the coding region corresponded to synonymous mutations,
and only the ORF3 showed a positive selection. Further, analyses are needed to
understand the clinical significance of HEV genotypes and subtypes.
PMID- 26415754
TI - Ribosomal protein L4 interacts with viral protein VP3 and regulates the
replication of infectious bursal disease virus.
AB - VP3 protein is a structural protein which plays important roles in the virus
assembly and the inhibition of antiviral innate immunity of infectious bursal
disease virus (IBDV). To explore the potential roles of VP3 in the interplay of
IBDV with the host cell, an immunoprecipitation (IP)-coupled mass spectra (MS)
screening was performed and the host cellular ribosomal protein L4 (RPL4) was
identified as a putative interacting partner of VP3 protein. The interaction of
RPL4 with VP3 was further confirmed by co-immunoprecipitation (co-IP) and their
colocalization in DF1 cells were observed by confocal microscopy. In addition,
knockdown of RPL4 in DF1 cells resulted in reductions of the viral protein pVP2
expression and the virus titers, which reveals a significant role of RPL4 in IBDV
replication. Taken together, we indicated for the first time that ribosomal
protein L4 (RPL4) was an interacting partner of VP3 and involved in the
modulation of IBDV replication. The present study contributes to further
understanding the pathogenic mechanism of IBDV.
PMID- 26415755
TI - Generation of a recombinant West Nile virus stably expressing the Gaussia
luciferase for neutralization assay.
AB - West Nile virus (WNV) is a neurotropic human pathogen that has caused increasing
infected cases over recent years. There is currently no licensed vaccine or
effective drug for prevention and treatment of WNV infection in humans. To
facilitate antiviral drug discovery and neutralizing antibody detection, a WNV
cDNA clone containing a luciferase reporter gene was constructed through
incorporating Gaussia luciferase (Gluc) gene within the capsid-coding region of
WNV genome. Transfection of BHK-21 cells with the cDNA clone-derived RNA
generated luciferase reporter WNV (WNV-Gluc) and the stable WNV-Gluc with high
titers (>10(7)PFU/ml) was obtained through plaque purification. Luciferase
activity was used to effectively quantify the viral production of WNV-Gluc. Using
the reporter virus WNV-Gluc, we developed a luciferase based assay in a 12-well
format for evaluating neutralizing antibodies. The reporter virus could be a
powerful tool for epidemiological investigation of WNV, vaccine evaluation,
antiviral drug screening, and the study of WNV replication and pathogenesis.
PMID- 26415756
TI - A novel delivery platform based on Bacteriophage MS2 virus-like particles.
AB - Our objective here is to review the novel delivery platform based on
Bacteriophage MS2 virus-like particles (VLPs), including introduction to their
structure, their potential as a delivery platform, and their expected use in
medicine and other fields. Bacteriophage MS2 VLPs are nanoparticles devoid of
viral genetic material and can self-assemble from the coat protein into an
icosahedral capsid. As a novel delivery platform, they possess numerous features
that make them suitable and attractive for targeted delivery of RNAs or DNAs,
epitope peptides, and drugs within the protein capsid. In short, as a novel
delivery platform, MS2 VLPs are suitable for delivery of targeted agents and hold
promise for use in diagnostics, vaccines, and therapeutic modalities.
PMID- 26415757
TI - Understanding hikers who approached a hazardous river in Yosemite National Park.
AB - OBJECTIVES: To understand the perceptions and motivations of hikers who
approached a swift river at locations that have been associated with drowning in
the past. METHODS: A survey was completed by 399 adults who had been observed
getting 'too close' to the Merced River. The questionnaire covered trail
familiarity, information sources, timing and motivation of their decision,
perceived safety, knowledge and opinion of park rules. RESULTS: Sixty-eight per
cent of invited hikers agreed to participate. Almost all had received advance
information about their hike, but most often that did not include a river
warning. Most respondents were observed in the risk zone by the footbridge, and
their most frequent motivation was to 'cool off'. Ninety-two per cent of hikers
reported feeling very or somewhat safe by the river. Their risk perceptions did
not correlate with expert ratings of danger. Males, younger subjects and those
who had hiked the trail before were more likely to enter the most hazardous parts
of the risk zone. Eleven per cent of people at the footbridge and 43% at the top
of the waterfall thought that the park should not allow visitors to go where they
had been. The most common reason they gave for this view was that the location
was unsafe. CONCLUSIONS: While this needs assessment identified channels for
informing hikers of drowning risk, there are indications that they might not
personalise such warnings. Another option would be to explore cooling
alternatives that could compete with the swift water that runs along many hiking
trails.
PMID- 26415758
TI - Hybrid upconversion nanomaterials for optogenetic neuronal control.
AB - Nanotechnology-based approaches offer the chemical control required to develop
precision tools suitable for applications in neuroscience. We report a novel
approach employing hybrid upconversion nanomaterials, combined with the
photoresponsive ion channel channelrhodopsin-2 (ChR2), to achieve near-infrared
light (NIR)-mediated optogenetic control of neuronal activity. Current
optogenetic methodologies rely on using visible light (e.g. 470 nm blue light),
which tends to exhibit high scattering and low tissue penetration, to activate
ChR2. In contrast, our approach enables the use of 980 nm NIR light, which
addresses the short-comings of visible light as an excitation source. This was
facilitated by embedding upconversion nanomaterials, which can convert NIR light
to blue luminescence, into polymeric scaffolds. These hybrid nanomaterial
scaffolds allowed for NIR-mediated neuronal stimulation, with comparable
efficiency as that of 470 nm blue light. Our platform was optimized for NIR
mediated optogenetic control by balancing multiple physicochemical properties of
the nanomaterial (e.g. size, morphology, structure, emission spectra,
concentration), thus providing an early demonstration of rationally-designing
nanomaterial-based strategies for advanced neural applications.
PMID- 26415759
TI - Polysaccharide utilization locus and CAZYme genome repertoires reveal diverse
ecological adaptation of Prevotella species.
AB - The results of metagenomic studies have clearly established that bacteria of the
genus Prevotella represent one of the important groups found in the oral cavity
and large intestine of man, and they also dominate the rumen. They belong to the
Bacteroidetes, a phylum well-known for its polysaccharide degrading potential
that stems from the outer membrane-localized enzyme/binding protein complexes
encoded in polysaccharide utilization loci (PULs). Dozens of Prevotella species
have been described, primarily from the oral cavity, and many of them occur
simultaneously at the same sites, but research on their ecological adaptation has
been neglected. Therefore, in this study, the repertoires of PULs and
carbohydrate acting enzymes (CAZYmes) found in Prevotella genomes were analyzed
and it was concluded that the Prevotella species were widely heterogeneous in
this respect and displayed several distinct adaptations with regard to the
number, source and nature of the substrates apparently preferred for growth.
PMID- 26415760
TI - Trends in the growth of literature of telemedicine: A bibliometric analysis.
AB - Over the past two decades, the use of telemedicine as a way to provide medical
services has grown as communication technologies advance and patients seek more
convenient ways to receive care. Because developments within this field are still
rapidly evolving, identifying trends within telemedicine literature is an
important task to help delineate future directions of telemedicine research. In
this study, we analyzed 7960 telemedicine-related publication records found in
the Science Citations Index - Expanded database between 1993 and 2012.
Bibliometric analyses revealed that while the total growth in telemedicine
literature has been significant in the last twenty years, the publication
activity per country and over time has been variable. While the United States led
the world in the cumulative number of telemedicine publications, Norway ranked
highest when we ordered countries by publications per capita. We also saw that
the growth in the number of publications per year has been inconsistent over the
past two decades. Our results identified that neuroscience neurology and nursing
as two fields of research in telemedicine that have seen considerable growth in
interest in this field, and are poised to be the focus of research activity in
the near future.
PMID- 26415761
TI - Our experience in using the brachial venae comitantes as a native vascular access
for hemodialysis.
AB - A native arteriovenous fistula is the preferred vascular access for patients on
long-term hemodialysis. In the absence of suitable superficial veins, the deep
venous system can be used. We intend to present our experience in using the
brachial venae comitantes (VC) to create a native arteriovenous fistula. From
January 2012 to December 2014, we utilized the brachial vena comitantes to create
12 arteriovenous fistulae. Data from these 12 subjects were analyzed
retrospectively to produce this case series. The average age of our subjects was
55.6 years. Forty-two percent of the subjects were women. Fifty percent of the
subjects had diabetes mellitus and 58% had hypertension. We achieved a functional
patency rate of 58% at 1 month's follow up after maturation. The brachio-brachial
vena comitans fistula is a safe and plausible option in patients with no other
suitable veins for a native fistula, more so in the hands of experienced
surgeons. The longer time to cannulation has to be taken into consideration when
creating a VC fistula. In suitable patients with end-stage renal disease, it can
delay the use of an arteriovenous graft or a tunneled central venous catheter.
PMID- 26415762
TI - Vitamin C supplementation in pregnancy.
AB - BACKGROUND: Vitamin C supplementation may help reduce the risk of pregnancy
complications such as pre-eclampsia, intrauterine growth restriction and maternal
anaemia. There is a need to evaluate the efficacy and safety of vitamin C
supplementation in pregnancy. OBJECTIVES: To evaluate the effects of vitamin C
supplementation, alone or in combination with other separate supplements on
pregnancy outcomes, adverse events, side effects and use of health resources.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
Register (31 March 2015) and reference lists of retrieved studies. SELECTION
CRITERIA: All randomised or quasi-randomised controlled trials evaluating vitamin
C supplementation in pregnant women. Interventions using a multivitamin
supplement containing vitamin C or where the primary supplement was iron were
excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
trials for inclusion and risk of bias, extracted data and checked them for
accuracy. MAIN RESULTS: Twenty-nine trials involving 24,300 women are included in
this review. Overall, 11 trials were judged to be of low risk of bias, eight were
high risk of bias and for 10 trials it was unclear. No clear differences were
seen between women supplemented with vitamin C alone or in combination with other
supplements compared with placebo or no control for the risk of stillbirth (risk
ratio (RR) 1.15, 95% confidence intervals (CI) 0.89 to 1.49; 20,038 participants;
11 studies; I2 = 0%; moderate quality evidence), neonatal death (RR 0.79, 95% CI
0.58 to 1.08; 19,575 participants; 11 studies; I2 = 0%), perinatal death (average
RR 1.07, 95% CI 0.77 to 1.49; 17,105 participants; seven studies; I2 = 35%),
birthweight (mean difference (MD) 26.88 g, 95% CI -18.81 to 72.58; 17,326
participants; 13 studies; I2 = 69%), intrauterine growth restriction (RR 0.98,
95% CI 0.91 to 1.06; 20,361 participants; 12 studies; I2 = 15%; high quality
evidence), preterm birth (average RR 0.99, 95% CI 0.90 to 1.10; 22,250
participants; 16 studies; I2 = 49%; high quality evidence), preterm PROM
(prelabour rupture of membranes) (average RR 0.98, 95% CI 0.70 to 1.36; 16,825
participants; 10 studies; I2 = 70%; low quality evidence), term PROM (average RR
1.26, 95% CI 0.62 to 2.56; 2674 participants; three studies; I2 = 87%), and
clinical pre-eclampsia (average RR 0.92, 95% CI 0.80 to 1.05; 21,956
participants; 16 studies; I2 = 41%; high quality evidence).Women supplemented
with vitamin C alone or in combination with other supplements compared with
placebo or no control were at decreased risk of having a placental abruption (RR
0.64, 95% CI 0.44 to 0.92; 15,755 participants; eight studies; I2 = 0%; high
quality evidence) and had a small increase in gestational age at birth (MD 0.31,
95% CI 0.01 to 0.61; 14,062 participants; nine studies; I2 = 65%), however they
were also more likely to self-report abdominal pain (RR 1.66, 95% CI 1.16 to
2.37; 1877 participants; one study). In the subgroup analyses based on the type
of supplement, vitamin C supplementation alone was associated with a reduced risk
of preterm PROM (average RR 0.66, 95% CI 0.48 to 0.91; 1282 participants; five
studies; I2 = 0%) and term PROM (average RR 0.55, 95% CI 0.32 to 0.94; 170
participants; one study). Conversely, the risk of term PROM was increased when
supplementation included vitamin C and vitamin E (average RR 1.73, 95% CI 1.34 to
2.23; 3060 participants; two studies; I2 = 0%). There were no differences in the
effects of vitamin C on other outcomes in the subgroup analyses examining the
type of supplement. There were no differing patterns in other subgroups of women
based on underlying risk of pregnancy complications, timing of commencement of
supplementation or dietary intake of vitamin C prior to trial entry. The GRADE
quality of the evidence was high for intrauterine growth restriction, preterm
birth, and placental abruption, moderate for stillbirth and clinical pre
eclampsia, low for preterm PROM. AUTHORS' CONCLUSIONS: The data do not support
routine vitamin C supplementation alone or in combination with other supplements
for the prevention of fetal or neonatal death, poor fetal growth, preterm birth
or pre-eclampsia. Further research is required to elucidate the possible role of
vitamin C in the prevention of placental abruption and prelabour rupture of
membranes. There was no convincing evidence that vitamin C supplementation alone
or in combination with other supplements results in other important benefits or
harms.
PMID- 26415763
TI - A conceptual framework for economic optimization of an animal health surveillance
portfolio.
AB - Decision making on hazard surveillance in livestock product chains is a multi
hazard, multi-stakeholder, and multi-criteria process that includes a variety of
decision alternatives. The multi-hazard aspect means that the allocation of the
scarce resource for surveillance should be optimized from the point of view of a
surveillance portfolio (SP) rather than a single hazard. In this paper, we
present a novel conceptual approach for economic optimization of a SP to address
the resource allocation problem for a surveillance organization from a
theoretical perspective. This approach uses multi-criteria techniques to evaluate
the performances of different settings of a SP, taking cost-benefit aspects of
surveillance and stakeholders' preferences into account. The credibility of the
approach has also been checked for conceptual validity, data needs and
operational validity; the application potentials of the approach are also
discussed.
PMID- 26415764
TI - Associations of infant milk feed type on early postnatal growth of offspring
exposed and unexposed to gestational diabetes in utero.
AB - PURPOSE: Infants on prolonged breastfeeding are known to grow slower during the
first year of life. It is still unclear if such effects are similar in offspring
exposed to gestational diabetes (GDM) in utero. We examined the associations of
infant milk feeding on postnatal growth from birth till 36 months of age in
offspring exposed and unexposed to GDM. METHODS: Pregnant mothers undertook 75 g
2-h oral glucose tolerance tests at 26-28 weeks of gestation for GDM diagnosis.
Up to 9 measurements of offspring weight and length were collected from birth
till 36 months, and interviewer-administered questionnaires were used to
ascertain the duration of breastfeeding. RESULTS: There was a statistically
significant interaction between GDM status and breastmilk intake by any (p
interaction = 0.038) or exclusive/predominant breastfeeding (p interaction =
0.035) for the outcome of conditional weight gain. In offspring of non-GDM
mothers (n = 835), greater breastmilk intake (BF >= 4 milk months) was associated
with lower conditional gains in weight [B (95 % CI) -0.48 (-0.58, -0.28); p <
0.001] within the first year of life, as well as decreasing weight SDS velocity [
0.01 (-0.02, -0.005); p < 0.001] and BMI SDS velocity [-0.008 (0.01, -0.002); p =
0.008] across age in the first 36 months. In offspring of GDM mothers (n = 181),
however, greater breastmilk intake was associated with increased conditional
gains in weight [0.72 (0.23, 1.20); p = 0.029] and BMI SDS [0.49 (0.04, 0.95); p
= 0.04] in the first 6 months and did not demonstrate the decreasing weight and
BMI SDS velocity observed in offspring of non-GDM mothers. CONCLUSIONS: The
reduced weight gain in the first year of life conferred by greater breastmilk
intake in non-GDM children was not observed in GDM children. CLINICAL TRIAL
REGISTRATION: This study is registered under the Clinical Trials identifier
NCT01174875; http://www.clinicaltrials.gov/ct2/show/NCT01174875?term=GUSTO&rank=2
.
PMID- 26415765
TI - Inflammatory mediator-induced modulation of GABAA currents in human sensory
neurons.
AB - The purpose of the present study was to characterize the properties of A-type
GABA receptor (GABAA receptor) currents in human sensory neurons. Neurons were
obtained from adult organ donors. GABAA currents were recorded in isolated
neurons. Both large inactivating low-affinity currents and smaller persistent
high-affinity currents were present in all of the 129 neurons studied from 15
donors. The kinetics of human GABAA currents were slower than those in rat
sensory neurons. GABA currents were completely blocked by bicuculline (10 MUM),
and persistent currents were activated by the delta-subunit-preferring agonist,
4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol (THIP). The GABA current
equilibrium potential was ~ 20 mV more hyperpolarized than in rat neurons. Both
low- and high-affinity currents were increased by inflammatory mediators but via
different second messenger pathways. These results highlight potentially
important species differences in the properties of ion channels present in their
native environment and suggest the use of human sensory neurons may be a valuable
tool to test compounds prior to use in humans.
PMID- 26415766
TI - Effects of chronic peripheral olfactory loss on functional brain networks.
AB - The effects of sensory loss on central processing in various sensory systems have
already been described. The olfactory system holds the special ability to be
activated by a sensorimotor act, without the presentation of an odor. In this
study, we investigated brain changes related to chronic peripheral smell loss. We
included 11 anosmic patients (eight female, three male; mean age, 43.5 years)
with smell loss after an infection of the upper respiratory tract (mean disease
duration, 4.64 years) and 14 healthy controls (seven female, seven male; mean
age, 30.1 years) in a functional magnetic resonance imaging experiment with a
sniffing paradigm. Data were analyzed using group-independent component analysis
and functional connectivity analysis. Our results revealed a spatially intact
olfactory network in patients, whereas major aberrations due to peripheral loss
were observed in functional connectivity through a variety of distributed brain
areas. This is the first study to show the re-organization caused by the lack of
peripheral input. The results of this study indicate that anosmic patients hold
the ability to activate an olfaction-related functional network through the
sensorimotor component of odor-perception (sniffing). The areas involved were not
different from those that emerged in healthy controls. However, functional
connectivity appears to be different between the two groups, with a decrease in
functional connectivity in the brain in patients with chronic peripheral sensory
loss. We can further conclude that the loss of the sense of smell may induce far
reaching effects in the whole brain, which lead to compensatory mechanisms from
other sensory systems due to the close interconnectivity of the olfactory system
with other functional networks.
PMID- 26415767
TI - Phoenixin: A candidate pruritogen in the mouse.
AB - Phoenixin (PNX) is a 14-amino acid amidated peptide (PNX-14) or an N-terminal
extended 20-residue amidated peptide (PNX-20) recently identified in neural and
non-neural tissue. Mass spectrometry analysis identified a major peak
corresponding to PNX-14, with negligible PNX-20, in mouse spinal cord extracts.
Using a previously characterized antiserum that recognized both PNX-14 and PNX
20, PNX-immunoreactivity (irPNX) was detected in a population of dorsal root
ganglion (DRG) cells and in cell processes densely distributed to the superficial
layers of the dorsal horn; irPNX cell processes were also detected in the skin.
The retrograde tracer, Fluorogold, injected subcutaneously (s.c.) to the back of
the cervical and thoracic spinal cord of mice, labeled a population of DRG, some
of which were also irPNX. PNX-14 (2, 4 and 8 mg/kg) injected s.c.to the nape of
the neck provoked dose-dependent repetitive scratching bouts directed to the back
of the neck with the hindpaws. The number of scratching bouts varied from 16 to
95 in 30 min, commencing within 5 min post-injection and lasted 10-15 min.
Pretreatment of mice at -20 min with nalfurafine (20 MUg/kg, s.c.), the kappa
opioid receptor agonist, significantly reduced the number of bouts induced by PNX
14 (4 mg/kg) compared with that of saline-pretreated mice. Our results suggest
that the peptide, PNX-14, serves as one of the endogenous signal molecules
transducing itch sensation in the mouse.
PMID- 26415768
TI - Protection against cognitive impairment and modification of epileptogenesis with
curcumin in a post-status epilepticus model of temporal lobe epilepsy.
AB - Epileptogenesis is a dynamic process initiated by insults to the brain that is
characterized by progressive functional and structural alterations in certain
cerebral regions, leading to the appearance of spontaneous recurrent seizures.
Within the duration of the trauma to the brain and the appearance of spontaneous
recurrent seizures, there is typically a latent period, which may offer a
therapeutic window for preventing the emergence of epilepsy. Previous animal
studies have shown that curcumin can attenuate acute seizure severity and brain
oxidative stress, but the effect of curcumin on epileptogenesis has not been
studied. We examined the effect of continued administration of curcumin during
the latent period on epileptogenesis and the deleterious consequences of status
epilepticus in adult rats in a post-status epilepticus model of temporal lobe
epilepsy induced by kainic acid. We demonstrate that, while administration of
curcumin treatment during the latent period does not prevent occurrence of
spontaneous recurrent seizures after status epilepticus, it can attenuate the
severity of spontaneous recurrent seizures and protect against cognitive
impairment. Thus, treatment with curcumin during the latent period following
status epilepticus is beneficial in modifying epileptogenesis.
PMID- 26415769
TI - New uses of LFPs: Pathway-specific threads obtained through spatial
discrimination.
AB - Local field potentials (LFPs) reflect the coordinated firing of functional neural
assemblies during information coding and transfer across neural networks. As
such, it was proposed that the extraordinary variety of cytoarchitectonic
elements in the brain is responsible for the wide range of amplitudes and for the
coverage of field potentials, which in most cases receive contributions from
multiple pathways and populations. The influence of spatial factors overrides the
bold interpretations of customary measurements, such as the amplitude and
polarity, to the point that their cellular interpretation is one of the hardest
tasks in Neurophysiology. Temporal patterns and frequency bands are not exclusive
to pathways but rather, the spatial configuration of the voltage gradients
created by each pathway is highly specific and may be used advantageously. Recent
technical and analytical advances now make it possible to separate and then
reconstruct activity for specific pathways. In this review, we discuss how
spatial features specific to cells and populations define the amplitude and
extension of LFPs, why they become virtually indecipherable when several pathways
are co-activated, and then we present the recent advances regarding their
disentanglement using spatial discrimination techniques. The pathway-specific
threads of LFPs have a simple cellular interpretation, and the temporal
fluctuations obtained can be applied to a variety of new experimental objectives
and improve existing approaches. Among others, they facilitate the parallel
readout of activity in several populations over multiple time scales correlating
them with behavior. Also, they access information contained in irregular
fluctuations, facilitating the testing of ongoing plasticity. In addition, they
open the way to unravel the synaptic nature of rhythmic oscillations, as well as
the dynamic relationships between multiple oscillatory activities. The challenge
of understanding which waves belong to which populations, and the pathways that
provoke them, may soon be overcome.
PMID- 26415770
TI - An optimized method for measuring hypocretin-1 peptide in the mouse brain reveals
differential circadian regulation of hypocretin-1 levels rostral and caudal to
the hypothalamus.
AB - The hypocretin/orexin system regulates, among other things, sleep and energy
homeostasis. The system is likely regulated by both homeostatic and circadian
mechanisms. Little is known about local differences in the regulation of
hypocretin activity. The aim of this study was to establish an optimized peptide
quantification method for hypocretin-1 extracted from different mouse brain areas
and use this method for investigating circadian fluctuations of hypocretin-1
levels in these areas. The results show that hypocretin-1 peptide can be
extracted from small pieces of intact tissue, with sufficient yield for
measurements in a standard radioimmunoassay. Utilizing the optimized method, it
was found that prepro-hypocretin mRNA and peptide show circadian fluctuations in
the mouse brain. This study further demonstrates that the hypocretin-1 peptide
level in the frontal brain peaks during dark as does prepro-hypocretin mRNA in
the hypothalamus. However, in midbrain and brainstem tissue caudal to the
hypothalamus, there was less circadian fluctuation and a tendency for higher
levels during the light phase. These data suggest that regulation of the
hypocretin system differs between brain areas.
PMID- 26415771
TI - Anchoring the "floating arm": Use of proprioceptive and mirror visual feedback
from one arm to control involuntary displacement of the other arm.
AB - Arm movement control takes advantage of multiple inputs, including those
originating from the contralateral arm. In the mirror paradigm, it has been
suggested that control of the unseen arm, hidden by the mirror, is facilitated by
the reflection of the other, moving arm. Although proprioceptive feedback
originating from the moving arm, (the image of which is reflected in the mirror),
is always coupled with visual feedback in the mirror paradigm, the former has
received little attention. We recently showed that the involuntary arm movement
following a sustained, isometric contraction, known as the "floating arm" or
"Kohnstamm phenomenon", was adjusted to the passive-motorized displacement of the
other arm. However, provision of mirror feedback, that is, the reflection in the
mirror of the passively moved arm, did not add to this coupling effect.
Therefore, the interlimb coupling in the mirror paradigm may to a large extent
have a proprioceptive origin rather than a visual origin. The objective of the
present study was to decouple mirror feedback and proprioceptive feedback from
the reflected, moving arm and evaluate their respective contributions to
interlimb coupling in the mirror paradigm. First (in Experiment 1, under eyes
closed conditions), we found that masking the proprioceptive afferents of the
passively moved arm (by co-vibrating the antagonistic biceps and triceps muscles)
suppressed the interlimb coupling between involuntary displacement of one arm and
passive displacement of the other. Next (in Experiment 2), we masked
proprioceptive afferents of the passively moved arm and specifically evaluated
mirror feedback. We found that interlimb coupling through mirror feedback (though
significant) was weaker than interlimb coupling through proprioceptive feedback.
Overall, the present results show that in the mirror paradigm, proprioceptive
feedback is stronger and more consistent than visual-mirror feedback in terms of
the impact on interlimb coupling.
PMID- 26415773
TI - PROGRAM.
PMID- 26415772
TI - Overexpression of alphaCaMKII impairs behavioral flexibility and NMDAR-dependent
long-term depression in the medial prefrontal cortex.
AB - The medial prefrontal cortex (mPFC) participates in the behavioral flexibility.
As a major downstream molecule in the NMDA receptor signaling, alpha
Ca(2+)/calmodulin-dependent protein kinase II (alphaCaMKII) is crucial for
hippocampal long-term potentiation (LTP) and hippocampus-related memory. However,
the role of alphaCaMKII in mPFC-related behavioral flexibility and mPFC synaptic
plasticity remains elusive. In the present study, using chemical-genetic
approaches to temporally up-regulate alphaCaMKII activity, we found that
alphaCaMKII-F89G transgenic mice exhibited impaired behavioral flexibility in Y
water maze arm reversal task. Notably, in vitro electrophysiological analysis
showed normal basal synaptic transmission, LTP and depotentiation, but
selectively impaired NMDAR-dependent long-term depression (LTD) in the mPFC of
alphaCaMKII-F89G transgenic mice. In accordance with the deficit in NMDAR
dependent LTD, alphaCaMKII-F89G transgenic mice exhibited impaired AMPAR
internalization during NMDAR-dependent chemical LTD expression in the mPFC.
Furthermore, the above deficits in behavioral flexibility, NMDAR-dependent LTD
and AMPAR internalization could all be reversed by 1-naphthylmethyl (NM)-PP1, a
specific inhibitor of exogenous alphaCaMKII-F89G activity. Taken together, our
results for the first time indicate that alphaCaMKII overexpression in the
forebrain impairs behavioral flexibility and NMDAR-dependent LTD in the mPFC, and
supports the notion that there is a close relationship between NMDAR-dependent
LTD and behavioral flexibility.
PMID- 26415774
TI - Increased epigenetic alterations at the promoters of transcriptional regulators
following inadequate maternal gestational weight gain.
AB - Epigenetic modifications are thought to serve as a memory of exposure to in utero
environments. However, few human studies have investigated the associations
between maternal nutritional conditions during pregnancy and epigenetic
alterations in offspring. In this study, we report genome-wide methylation
profiles for 33 postpartum placentas from pregnancies of normal and foetal growth
restriction with various extents of maternal gestational weight gain. Epigenetic
alterations accumulate in the placenta under adverse in utero environments, as
shown by application of Smirnov-Grubbs' outlier test. Moreover, hypermethylation
occurs frequently at the promoter regions of transcriptional regulator genes,
including polycomb targets and zinc-finger genes, as shown by annotations of the
genomic and functional features of loci with altered DNA methylation. Aberrant
epigenetic modifications at such developmental regulator loci, if occurring in
foetuses as well, will elevate the risk of developing various diseases, including
metabolic and mental disorders, later in life.
PMID- 26415776
TI - Enhanced efficacy of chemotherapy for breast cancer stem cells by simultaneous
suppression of multidrug resistance and antiapoptotic cellular defense.
AB - While chemotherapy is universally recognized as a frontline treatment strategy
for breast cancer, it is not always successful; among the leading causes of
treatment failure is existing and/or acquired multidrug resistance. Cancer stem
cells (CSCs), which constitute a minority of the cells of a tumor, are
acknowledged to be responsible for increased resistance to chemo-drugs through a
combination of increased expression of ATP-binding cassette transporters (ABC
transporters), an increased anti-apoptotic defense, and/or the ability for
extensive DNA repair like normal stem cells. Consequently, more effective
therapy, especially targeted to CSCs, is urgently required. We studied the
characteristics of 231-CSCs (CD44+/CD24-) sorted from human MDA-MB-231 breast
cancer cells and demonstrated that 231-CSCs exhibited enhanced capacities for
proliferation, migration, tumorigenesis and chemotherapy resistance. To address
these multifunctional facets of CSCs, we devised a non-ionic surfactant-based
vesicle (niosome) co-delivery system to simultaneously deliver siRNAs, targeted
to both the ABC transporter (ABCG2) and the anti-apoptosis defense gene (BCL2),
and doxorubicin (DOX) to CSCs. The rationale is to sensitize CSCs to DOX by down
regulating the drug-resistance gene ABCG2 and simultaneously induce apoptosis by
lowering BCL2 expression. The co-delivery system (CDS) successfully delivered
siRNAs and DOX to the cytoplasm and nuclei, respectively, and resulted in a down
regulation of ABCG2- and BCL2 mRNAs in CSCs by 60% and 65%, respectively,
compared to the control. A corresponding decrease in protein expression was
observed using Western blotting. The IC50 of DOX in CSCs concurrently decreased
significantly. Our result established CDS as a promising multi-drug delivery
platform for cancer treatment. STATEMENT OF SIGNIFICANCE: Cancer stem cells
(CSCs) are acknowledged to be responsible for increased resistance to chemo-drugs
through a combination of increased expression of ABC transporters, an increased
anti-apoptotic defense, and/or the ability for extensive DNA repair like normal
stem cells. Consequently, effective therapy, especially to CSCs, is urgently
required. In current study, we studied the characteristics of 231-CSCs sorted
from human MDA-MB-231 breast cancer cells and found that 231-CSCs possessed
enhanced proliferation, migration, tumorigenesis, and DOX resistance. We employed
a non-ionic surfactant-based vesicle (niosome) delivery system to simultaneously
deliver siRNAs targeted to multi-drug resistance genes, and DOX to kill 231-CSCs.
The CDS showed an enhanced therapeutic effect by resensitizing 231-CSCs to DOX
and may constitute a promising candidate for cancer chemotherapy.
PMID- 26415777
TI - Contribution of fibronectin and vitronectin to the adhesion and morphology of
MC3T3-E1 osteoblastic cells to poly(NaSS) grafted Ti6Al4V.
AB - This study is focused on understanding the underlying mechanisms involved in the
improved in vitro and in vivo responses of osteoblasts on poly(sodium styrene
sulfonate) (poly(NaSS)) functionalized Ti6Al4V surfaces. We probed the
contribution of cell-adhesive glycoproteins fibronectin (Fn) and vitronectin (Vn)
in the initial adhesion of MC3T3-E1 osteoblastic cells to poly(NaSS)
functionalized and control Ti6Al4V surfaces. Firstly, culture media containing
serum depleted of Fn and Vn (DD) were used to establish the contribution of Fn
and Vn in the adhesion and spreading of cells on poly(NaSS) grafted and control
surfaces. Compared to ungrafted surfaces, poly(NaSS) grafted surfaces enhanced
the levels of cell adhesion, cell spreading and the formation of intracellular
actin cytoskeleton and focal contacts in serum treatments where Fn or Vn were
present (FBS, DD+Fn, DD+Vn). Cell responses to Fn were more significant than to
Vn. Secondly, blocking Fn and Vn integrin receptors using antibodies to
alpha5beta1 (Fn) and alphavbeta1 (Vn) showed that adhesion of cells to poly(NaSS)
grafted surfaces principally involved the Fn integrin receptor alpha5beta1.
Thirdly, blocking of the heparin and cell-binding regions of Fn molecule (RGD, C
HB, N-HB) showed that grafting with poly(NaSS) altered the conformation of Fn.
Together these outcomes explained why the presence of sulfonate (SO3(-)) groups
grafted on the Ti6Al4V surface enhanced the early cell adhesion and spreading
processes which determine clinical success for applications that require
osseointegration. STATEMENT OF SIGNIFICANCE: This study is devoted to the basic
analysis of the mechanism at the origin of the improved in vitro and in vivo
osteoblast cell responses exhibited by poly(sodium styrene sulfonate)
(poly(NaSS)) functionalized Ti6Al4V surfaces. The aim was to probe the
contribution of cell adhesive glycoproteins fibronectin and vitronectin in the
initial adhesion of MC3T3-E1 osteoblastic cells to poly(NaSS) functionalized
Ti6Al4V surfaces. The outcomes of this research explained why the presence of
SO3(-) (sulfonate) groups grafted on the Ti6Al4V surface enhanced the early cell
adhesion and spreading processes which determine clinical success for
applications that require osseointegration. This work is a step further in the
research of poly(NaSS), a very promising bioactive polymer with potential to the
orthopedic and dental fields.
PMID- 26415775
TI - Heterochromatin Protein 1beta (HP1beta) has distinct functions and distinct
nuclear distribution in pluripotent versus differentiated cells.
AB - BACKGROUND: Pluripotent embryonic stem cells (ESCs) have the unique ability to
differentiate into every cell type and to self-renew. These characteristics
correlate with a distinct nuclear architecture, epigenetic signatures enriched
for active chromatin marks and hyperdynamic binding of structural chromatin
proteins. Recently, several chromatin-related proteins have been shown to
regulate ESC pluripotency and/or differentiation, yet the role of the major
heterochromatin proteins in pluripotency is unknown. RESULTS: Here we identify
Heterochromatin Protein 1beta (HP1beta) as an essential protein for proper
differentiation, and, unexpectedly, for the maintenance of pluripotency in ESCs.
In pluripotent and differentiated cells HP1beta is differentially localized and
differentially associated with chromatin. Deletion of HP1beta, but not HP1alpha,
in ESCs provokes a loss of the morphological and proliferative characteristics of
embryonic pluripotent cells, reduces expression of pluripotency factors and
causes aberrant differentiation. However, in differentiated cells, loss of
HP1beta has the opposite effect, perturbing maintenance of the differentiation
state and facilitating reprogramming to an induced pluripotent state. Microscopy,
biochemical fractionation and chromatin immunoprecipitation reveal a diffuse
nucleoplasmic distribution, weak association with chromatin and high expression
levels for HP1beta in ESCs. The minor fraction of HP1beta that is chromatin-bound
in ESCs is enriched within exons, unlike the situation in differentiated cells,
where it binds heterochromatic satellite repeats and chromocenters. CONCLUSIONS:
We demonstrate an unexpected duality in the role of HP1beta: it is essential in
ESCs for maintaining pluripotency, while it is required for proper
differentiation in differentiated cells. Thus, HP1beta function both depends on,
and regulates, the pluripotent state.
PMID- 26415778
TI - Plant diversity shapes microbe-rhizosphere effects on P mobilisation from organic
matter in soil.
AB - Plant species richness (PSR) increases nutrient uptake which depletes
bioavailable nutrient pools in soil. No such relationship between plant uptake
and availability in soil was found for phosphorus (P). We explored PSR effects on
P mobilisation [phosphatase activity (PA)] in soil. PA increased with PSR. The
positive PSR effect was not solely due to an increase in Corg concentrations
because PSR remained significant if related to PA:Corg . An increase in PA per
unit Corg increases the probability of the temporal and spatial match between
substrate, enzyme and microorganism potentially serving as an adaption to
competition. Carbon use efficiency of microorganisms (Cmic :Corg ) increased with
increasing PSR while enzyme exudation efficiency (PA:Cmic ) remained constant.
These findings suggest the need for efficient C rather than P cycling underlying
the relationship between PSR and PA. Our results indicate that the coupling
between C and P cycling in soil becomes tighter with increasing PSR.
PMID- 26415779
TI - Reply from Authors re: Tracy L. Rose, Matthew I. Milowsky. A Small Step Toward
Improving Salvage Treatment for Metastatic Bladder Cancer--At What Cost? Eur Urol
2016;69:642-44: Combination Chemotherapy as a Viable Salvage Therapy Strategy for
Advanced Urothelial Carcinoma.
PMID- 26415780
TI - What are the perspectives for technology platforms in the field of neuroscience?
PMID- 26415781
TI - Thresholds for self-motion perception in roll without and with visual fixation
target--the visualvestibular interaction effect.
AB - The purpose of this study was to establish the selfmotion perception threshold,
in roll, in the visualvestibular interaction (VVI) state, creating an oculogyral
illusion, and to compare this threshold to the self-motion perception threshold
in darkness. A further aim was to investigate the dynamics of the threshold at a
low frequency range (0.1-1 Hz) of sinusoidal rotation. Seven healthy subjects
were tested. A motion platform was used to generate motion. Single cycles of
sinusoidal acceleration at four frequencies (0.1, 0.2, 0.5 and 1 Hz) were used as
motion stimuli. To avoid otolith stimulation, subjects were rotated about a
vertical axis in supine position. To evoke an oculogyral illusion subjects were
instructed to fixate their gaze on a cross-shaped object aligned with their head,
which rotated with them. The results show a lowering of the self-motion
perception threshold in the VVI state, significant for the frequencies 0.1 and
0.2 Hz (p<0.05). In all the subjects, visual fixation on the cross evoked an
oculogyral illusion. The threshold in both tested conditions was frequency
dependent: it decreased with increasing frequency values. However, this effect
was consistently stronger in darkness across all frequencies (p<0.05). In
conclusion, the application of sinusoidal rotation during roll at low frequencies
in the VVI condition evokes oculogyral illusion. This interaction lowers the self
motion perception threshold compared to that measured during rotation in
darkness. This testing method could be of practical benefit in clinical
application for revealing brain dysfunction involving integrative mechanisms of
perception.
PMID- 26415782
TI - Effects of dispositional optimism on quality of life, emotional distress and
disability in Parkinson's disease outpatients under rehabilitation.
AB - This study was performed with the aim of assessing dispositional optimism (DO) in
a sample of Parkinson's disease (PD) patients, in order to evaluate its
association with clinical outcomes and its impact on rehabilitation. Before
entering an outpatient rehabilitation program, 58 participants suffering from
idiopathic PD completed the Life Orientation Test-Revised (LOT-R) to evaluate
their level of DO, the WHO-5 scale to evaluate their health-related quality of
life (HR-QoL), the Hospital Anxiety and Depression Scale (HADS) to identify
emotional distress, and the Barthel Index to evaluate their level of disability.
All the measures were repeated four months later, at their discharge from the
program. Disease stage and severity measures (Unified Parkinson's Disease Rating
Scale) were also taken into consideration. Correlations and multivariate
regression analyses compared DO with the health-related variables. On admission a
high level of DO was found to be associated with less severe disease, a better
quality of life (QoL) and lower emotional distress, but not with level of
disability (Barthel Index). Consistent results were found at discharge. The level
of DO di not change after rehabilitation, while anxiety was significantly
reduced, especially in subjects with low LOT-R and high HADS scores. The Barthel
Index values significantly improved. At discharge, participants with high DO
showed the best improvements in disability and in QoL. Effects of dispositional
optimism on quality of life, emotional distress and disability in Parkinson's
disease outpatients under rehabilitation In conclusion, a high level of DO was
associated with QoL, HADS and UPDRS both on admission and at discharge. The level
of DO remained stable after rehabilitation, while disability and anxiety were
reduced. Participants with high DO generally had better QoL, and better clinical
and psychological performances.
PMID- 26415783
TI - Semantic profiles in mild cognitive impairment associated with Alzheimer's and
Parkinson's diseases.
AB - The temporal and the prefrontal cortices have different roles in semantic
information processing: the temporal lobe is where knowledge is stored (Graham
and Hodges, 1997), whereas the prefrontal cortex is more specifically involved in
executive aspects of semantic processing. Relatively little is known about the
semantic profiles of mild cognitive impairment (MCI) in Alzheimer's disease (AD)
and Parkinson's disease (PD). This observational study investigated naming and
semantic questionnaire performances in three groups of subjects: 10 patients with
the amnestic-type MCI prodrome of AD (aMCI), 10 patients with early-stage
executive-type MCI in PD (MCI-PD), and 10 normal subjects. The MCI-PD subjects
demonstrated inferior performances on a semantic questionnaire, whereas the aMCI
group displayed modest difficulties in a naming task. These differences may be
explained by topographical differences in pathological involvement. Since the
frontal areas are more functionally impaired in PD, we hypothesize that the
semantic deficit may be a consequence of a deficiency in control of semantic
processing. On the other hand, the semantic deficit in aMCI may be related to a
lexical-semantic storage dysfunction resulting from pathological involvement of
the temporal lobe.
PMID- 26415784
TI - Preferential occurrence of attacks during night sleep and/or upon awakening
negatively affects migraine clinical presentation.
AB - It is well known that migraine attacks can preferentially occur during night
sleep and/or upon awakening, however the possible implications of this timing on
migraine clinical presentation remain unclear. The aim of this study was to
assess the possible consequences of sleep-related migraine (defined as >= 75% of
migraine attacks occurring during night sleep and/or upon awakening) on the
migraine clinical picture (i.e. migraine-related disability, attack severity, use
of symptomatic drugs), subjective sleep quality, excessive daytime sleepiness and
fatigue. Two hundred consecutive migraine without aura patients were enrolled;
patients with comorbid disorders or chronic medication use were excluded. 39% of
the migraineurs included in the study received a diagnosis of sleep-related
migraine. The mean frequency of migraine attacks (days per month) did not
significantly differ between the patients with and those without sleep-related
migraine, whereas migraine-related disability (p<0.0001), mean attack severity
(p<0.0001), and monthly intake of symptomatic drugs (p<0.0001) were significantly
higher in patients with migraine preferentially occurring at night-time and/or
upon awakening. Subjective sleep quality and excessive daytime sleepiness did not
differ significantly between the two groups, whereas fatigue was significantly
more present in the patients with sleep-related migraine (p=0.0001). These data
seem to support the hypothesis that patients with sleep-related migraine
represent a subset of individuals with a more severe and disabling clinical
presentation of migraine and greater impairment of daily functioning, as
suggested by the higher degree of fatigue. Migraineurs with night-time attacks
Preferential occurrence of attacks during night sleep and/or upon awakening
negatively affects migraine clinical presentation also showed a greater use of
symptomatic drugs, possibly related to delayed use of symptomatic treatment. The
identification of subtypes of patients with a higher disability risk profile
could have crucial implications for individually tailored management of migraine
patients.
PMID- 26415786
TI - Sex differences in MDMA-induced toxicity in Sprague-Dawley rats.
AB - Recent evidence demonstrates that female subjects show exaggerated responses to
3,4-methylenedioxymethamphetamine (MDMA) compared with males. The aim of our
study was to evaluate sex differences and the role of endogenous gonadal hormones
on the effects of MDMA. Fifty-six intact and gonadectomized male and female
Sprague-Dawley rats were randomly assigned to either MDMA (5 mg/kg) or saline
treatment. Learning and memory were assessed using the Morris water maze (MWM).
The expression of Bax and Bcl-2 in the hippocampus was detected by Western
blotting. Behavioral analysis showed that MDMA led to memory impairment in both
male and female rats. The female rats showed more sensitivity to impairment than
the males, as assessed using all the memory parameters in the MWM. Ovariectomy
attenuated the MDMA-induced memory impairment. By contrast, orchiectomized rats
showed more impairment than MDMA-treated intact male rats. Bcl-2 and Bax were
down-regulated and up-regulated in MDMA-treated male and female rats,
respectively. MDMA treatment in the orchiectomized rats led to upregulation of
Bax and down-regulation of Bcl-2. Ovariectomy attenuated the MDMA-induced up
regulation of Bax and caused more expression of Bcl-2 compared with what was
observed in the MDMA-treated intact female rats. In summary, female rats showed
exaggerated responses to the effects of MDMA and this may be explained by
endogenous gonadal hormones.
PMID- 26415785
TI - TMS-evoked N100 responses as a prognostic factor in acute stroke.
AB - Rehabilitation programs, to be efficiently tailored, need clear prognostic
markers. In acute stroke, neurophysiological measures, such as motor evoked
potentials (MEPs), have been proposed, although with discordant results. The aim
of this study was to identify a reliable neurophysiological measure of recovery
in acute post-stroke individuals by combining MEPs and the N100 component of
transcranial magnetic stimulation-evoked potentials (TEPs). Nine acute post
stroke subjects were included. Clinical evaluation performed in the first week
after the event included administration of the European Stroke Scale and Barthel
Index and recording of MEPs and TEPs; administration of the clinical scales was
repeated after one and three months. The presence/absence of MEPs and TEPs showed
correlations with motor outcome. Individuals with a poorer outcome showed absence
of both MEPs and TEPs; absence of MEPs alone was related to a partial recovery.
Given the results of this exploratory study, further investigation is needed to
define the accuracy of combined use of MEPs and TEPs as an approach for
predicting motor recovery after acute stroke.
PMID- 26415787
TI - Encephalopathy with status epilepticus during sleep (ESES) induced by
oxcarbazepine in idiopathic focal epilepsy in childhood.
AB - Encephalopathy with status epilepticus during sleep (ESES) is an age-related
disorder characterized by neuropsychological regression, epilepsy and a typical
EEG pattern of continuous epileptiform activity (> 85%) during NREM sleep. Cases
of worsening or induction of ESES with phenytoin, carbamazepine and phenobarbital
have been reported. We describe a child with benign epilepsy with centrotemporal
spikes (BECTS) in whom treatment with oxcarbazepine (OXC) induced ESES. The
patient was studied through repeated clinical-neuropsychological evaluations and
24-hour EEG recordings. He was treated with OXC two months after epilepsy onset.
One month after starting OXC, he developed an abrupt and severe cognitive
deterioration. A 24-hour EEG and neuropsychological tests showed an
electroclinical picture compatible with ESES. Withdrawal of OXC and introduction
of other drugs were followed by a prompt improvement. Five months after ESES
onset, a 24-hour EEG was normal. Our report indicates that OXC can induce ESES in
BECTS.
PMID- 26415788
TI - "Boosting" in Paralympic athletes with spinal cord injury: doping without drugs.
AB - The intentional activation of autonomic dysreflexia (AD, also called "boosting"),
a practice sometimes used by athletes affected by spinal cord injury (SCI), is
banned by the International Paralympic Committee (IPC). Although various studies
have addressed doping and AD as separate issues, studies evaluating AD as a
doping method are lacking. The aim of this brief review is to contribute to
better understanding of the relationship between doping and AD. We conducted a
literature search of the PubMed database (from 1994 onwards). The key search
terms "autonomic dysreflexia" and "boosting" were crossreferenced with "sport
performance". The official Paralympic website was also viewed. AD is a potent
sympathetic reflex, due to a massive release of noradrenaline, that results in
marked vasoconstriction distal to the level of the lesion. Athletes with SCI
often self-inflict physical suffering in order to induce this phenomenon, which
carries high health risks (i.e., hypertension, cerebral hemorrhage, stroke and
sudden death). Boosting is a practice that can be compared to doping methods and
the IPC expressly prohibits it. Any deliberate attempt to induce AD, if detected,
will lead to disqualification from the sporting event and subsequent
investigation by the IPC Legal and Ethics Committee.
PMID- 26415789
TI - In situ loading of well-dispersed silver nanoparticles on nanocrystalline
magnesium oxide for real-time monitoring of catalytic reactions by surface
enhanced Raman spectroscopy.
AB - The surface-enhanced Raman spectroscopy (SERS) technique is of great importance
for insight into the transient reaction intermediates and mechanistic pathways
involved in heterogeneously catalyzed chemical reactions under actual reaction
conditions, especially in water. Herein, we demonstrate a facile method for in
situ synthesis of nanocrystalline magnesium oxide-Ag(0) (nano MgO-Ag(0)) hybrid
nanomaterials with dispersed Ag nanoparticles (Ag NPs) on the surface of
nanocrystalline magnesium oxide (nano MgO) via Sn(2+) linkage and reduction. As a
benefit from the synergy effect of nano MgO and Ag NPs, the nano MgO-Ag(0)
exhibited both excellent SERS and catalytic activities for the reduction of 4
nitrothiophenol in the presence of NaBH4. The nano MgO-Ag(0) was used for real
time monitoring of the catalytic reaction process of 4-nitrothiophenol to 4
aminothiophenol in an aqueous medium by observing the SERS signals of the
reactant, intermediate and final products. The intrinsic reaction kinetics and
reaction mechanism of this reaction were also investigated. This SERS-based
synergy technique provides a novel approach for quantitative in situ monitoring
of catalytic chemical reaction processes.
PMID- 26415790
TI - The Efficacy and Safety of Wenxin Keli in Patients with Frequent Premature
Ventricular Contractions: A Randomized, Double-blind, Placebo-controlled,
Parallel-group, Multicenter Trial.
AB - BACKGROUND: Premature ventricular contractions (PVCs) are common in the general
population, and frequent PVCs may result in the poor quality of life or even the
damage of cardiac function. We examined the efficacy and safety of a traditional
Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a
relatively large Chinese cohort. METHODS: We performed a randomized, double
blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200
eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin
Keli or the placebo for 4 weeks. The primary and secondary endpoint was the
change of PVC numbers and PVC-related symptoms after a 4-week treatment compared
with baseline, respectively. In addition, vital signs, laboratory values, and
electrocardiographic parameters were assessed in a safety analysis. RESULTS: At
the initial evaluation, no significant differences in the baseline
characteristics were observed between the Wenxin Keli group and the placebo
group. A smaller number of PVCs was observed after the 4-week treatment than at
baseline, in both the Wenxin Keli group (5686 +/- 5940 vs. 15,138 +/- 7597
beats/d, P < 0.001) and the placebo group (10,592 +/- 8009 vs. 14,529 +/- 5929
beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantli
greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In
a full analysis set, patients in the Wenxin Keli group exhibited significantly
higher total effective responses in the reduction of PVCs compared to those in
the placebo group (83.8% vs. 43.5%,P < 0.001). The per-protocol analysis yielded
similar results (83.0% vs. 39.3%,P < 0.001). Treatment with Wenxin Keli also
demonstrated superior performance compared to the placebo with respect to PVC
related symptoms. No severe adverse effects attributable to Wenxin Keli were
reported. CONCLUSIONS: Wenxin Keli treatment effectively reduced the overall
number of PVCs and alleviated PVC-related symptoms in patients without structural
heart diseases and had no severe side effects.
PMID- 26415791
TI - Quantitative Measurement of Cerebral Perfusion with Intravoxel Incoherent Motion
in Acute Ischemia Stroke: Initial Clinical Experience.
AB - BACKGROUND: Intravoxel incoherent motion (IVIM) has the potential to provide both
diffusion and perfusion information without an exogenous contrast agent, its
application for the brain is promising, however, feasibility studies on this are
relatively scarce. The aim of this study is to assess the feasibility of IVIM
perfusion in patients with acute ischemic stroke (AIS). METHODS: Patients with
suspected AIS were examined by magnetic resonance imaging within 24 h of symptom
onset. Fifteen patients (mean age was 68.7 +/- 8.0 years) who underwent arterial
spin labeling (ASL) and diffusion-weighted imaging (DWI) were identified as
having AIS with ischemic penumbra were enrolled, where ischemic penumbra referred
to the mismatch areas of ASL and DWI. Eleven different b-values were applied in
the biexponential model. Regions of interest were selected in ischemic penumbras
and contralateral normal brain regions. Fast apparent diffusion coefficients
(ADCs) and ASL cerebral blood flow (CBF) were measured. The paired t- test was
applied to compare ASL CBF, fast ADC, and slow ADC measurements between ischemic
penumbras and contralateral normal brain regions. Linear regression and Pearson's
correlation were used to evaluate the correlations among quantitative results.
RESULTS: The fast ADCs and ASL CBFs of ischemic penumbras were significantly
lower than those of the contralateral normal brain regions (1.93 +/- 0.78
alphaMUm2/ms vs. 3.97 +/- 2.49 alphaMUm2/ms, P = 0.007; 13.5 +/- 4.5 ml.100 g
1.min-1 vs. 29.1 +/- 12.7 ml.100 g-1.min-1, P < 0.001, respectively). No
significant difference was observed in slow ADCs between ischemic penumbras and
contralateral normal brain regions (0.203 +/- 0.090 alphaMUm2/ms vs. 0.198 +/-
0.100 alphaMUm2/ms, P = 0.451). Compared with contralateral normal brain regions,
both CBFs and fast ADCs decreased in ischemic penumbras while slow ADCs remained
the same. A significant correlation was detected between fast ADCs and ASL CBFs
(r = 0.416, P < 0.05). No statistically significant correlation was observed
between ASL CBFs and slow ADCs, or between fast ADCs and slow ADCs (r = 0.111, P
= 0.558; r = 0.200, P = 0.289, respectively). CONCLUSIONS: The decrease in
cerebral blood perfusion primarily results in the decrease in fast ADC in
ischemic penumbras; therefore, fast ADC can reflect the perfusion situation in
cerebral tissues.
PMID- 26415792
TI - Application of Minimum Effective Cuff Inflating Volume for Laryngeal Mask Airway
and its Impact on Postoperative Pharyngeal Complications.
AB - BACKGROUND: High intracuff pressure can cause severe pharyngeal complications
including sore throat or hoarseness after laryngeal mask airway (LMA) removal
postoperatively. Though the application of minimum effective cuff inflating
volume is suggested to maintain airway sealing and adequacy of ventilation for
patients receiving general anesthesia with LMA at lower level of the intracuff
pressure, it is currently not a standard care in most of the anesthetic
departments. In this study, the minimum effective cuff inflating volume was
determined for classic LMA Well LeadTM (Well Lead Medical Co., Ltd., China) and
its impact on postoperative pharyngeal complications was also explored. METHODS:
Patients with American Society of Anesthesiologists physical status (I-III)
undergoing the short-duration urological surgery were recruited in this trial.
First, the minimum effective cuff inflating volume was determined for size 4 or 5
LMA Well Lead in the study 1. Immediately following placement and confirmation of
ideal LMA position, the cuff was inflated with 5, 7, 10 ml of air and up to 30 ml
at 5 ml increment. The intracuff pressure, oropharyngeal leak pressure (OLP), and
inspiratory peak airway pressure under positive pressure ventilation at the
corresponding cuff volume as indicated above were recorded. Second, the enrolled
patients were randomly allocated into minimum effective cuff inflating volume
group (MC) and routine care (RC) group in the study 2. The minimum effective cuff
inflating volume was applied and maintained in MC group, whereas the cuff volume
was inflated with half of the maximum cuff inflating volume recommended by
manufacturer in RC group throughout the surgical procedure and stay in
postanesthesia care unit prior to LMA removal. The incidence of pharyngeal
complications at 0, 2, 24, and 48 h after removal of LMA and other intra
operative adverse events were also documented. RESULTS: The intracuff pressure
varied with the cuff inflating volume in a positive linear correlation manner (Y
= 11.68X - 42.1, r(2) = 0.9191) under the range of 5-30 ml for size 4 LMA. In
similar with size 4 LMA, the data were also showed the linear relationship
between the intracuff pressure and the cuff inflating volume (Y = 7.39X - 10.9,
r(2) = 0.8855) for size 5 LMA. The minimal effective cuff inflating volume for
size 4 or 5 LMA was 7-9 ml in combination of considering OLP needed to maintain
airway sealing during intermittently positive pressure ventilation. The intracuff
pressure in MC group was lower compared with RC group (63.0 +/- 3.7 vs. 126.4 +/-
24.0 cmH2O for size 4 LMA; 55.6 +/- 2.4 vs. 138.5+/- 26.8 cmH2O for size 5 LMA; P
< 0.0001). The incidence of pharyngeal adverse events was lower in MC group
versus the RC group at 2, 24 h after LMA removal. CONCLUSIONS: The relationship
between the cuff inflating volume and the intracuff pressure for size 4 or 5 LMA
Well Lead(TM) is in a linear correlation manner at the range of 5-30 ml. The
minimal cuff inflating volume is adequate for satisfactory airway sealing and
consequently associated with lower incidence of postoperative pharyngeal
complications for LMA Well Lead.TM.
PMID- 26415793
TI - The Dose-response of Intrathecal Ropivacaine Co-administered with Sufentanil for
Cesarean Delivery under Combined Spinal-epidural Anesthesia in Patients with
Scarred Uterus.
AB - BACKGROUND: Spinal anesthesia is considered as a reasonable anesthetic option in
lower abdominal and lower limb surgery. This study was to determine the dose
response of intrathecal ropivacaine in patients with scarred uterus undergoing
cesarean delivery under combined spinal-epidural anesthesia. METHODS: Seventy
five patients with scarred uterus undergoing elective cesarean delivery under
combined spinal-epidural anesthesia were enrolled in this randomized, double
blinded, dose-ranging study. Patients received 6, 8, 10, 12, or 14 mg intrathecal
hyperbaric ropivacaine with 5 MUg sufentanil. Successful spinal anesthesia was
defined as a T4sensory level achieved with no need for epidural supplementation.
The 50% effective dose (ED50) and 95% effective dose (ED95) were calculated with
a logistic regression model. RESULTS: ED50and ED95of intrathecal hyperbaric
ropivacaine for patients with scarred uterus undergoing cesarean delivery under
combined spinal-epidural anesthesia (CSEA) were 8.28 mg (95% confidence interval
[CI]: 2.28-9.83 mg) and 12.24 mg (95% CI: 10.53-21.88 mg), respectively.
CONCLUSION: When a CSEA technique is to use in patients with scarred uterus for
an elective cesarean delivery, the ED50and ED95of intrathecal hyperbaric
ropivacaine along with 5 MUg sufentanil were 8.28 mg and 12.24 mg, respectively.
In addition, this local anesthetic is unsuitable for emergent cesarean delivery,
but it has advantages for ambulatory patients.
PMID- 26415794
TI - The Application of an Anatomical Database for Fetal Congenital Heart Disease.
AB - BACKGROUND: Fetal congenital heart anomalies are the most common congenital
anomalies in live births. Fetal echocardiography (FECG) is the only prenatal
diagnostic approach used to detect fetal congenital heart disease (CHD). FECG is
not widely used, and the antenatal diagnosis rate of CHD varies considerably.
Thus, mastering the anatomical characteristics of different kinds of CHD is
critical for ultrasound physicians to improve FECG technology. The aim of this
study is to investigate the applications of a fetal CHD anatomic database in FECG
teaching and training program. METHODS: We evaluated 60 transverse section
databases including 27 types of fetal CHD built in the Prenatal Diagnosis Center
in Peking University People's Hospital. Each original database contained 400-700
cross-sectional digital images with a resolution of 3744 pixels * 5616 pixels. We
imported the database into Amira 5.3.1 (Australia Visage Imaging Company,
Australia) three-dimensional (3D) software. The database functions use a series
of 3D software visual operations. The features of the fetal CHD anatomical
database were analyzed to determine its applications in FECG continuing education
and training. RESULTS: The database was rebuilt using the 3D software. The
original and rebuilt databases can be displayed dynamically, continuously, and
synchronically and can be rotated at arbitrary angles. The sections from the
dynamic displays and rotating angles are consistent with the sections in FECG.
The database successfully reproduced the anatomic structures and spatial
relationship features of different fetal CHDs. We established a fetal CHD anatomy
training database and a standardized training database for FECG. Ultrasound
physicians and students can learn the anatomical features of fetal CHD and FECG
through either centralized training or distance education. CONCLUSIONS: The
database of fetal CHD successfully reproduced the anatomic structures and spatial
relationship of different kinds of fetal CHD. This database can be widely used in
anatomy and FECG teaching and training.
PMID- 26415795
TI - Lupus Myocarditis: A Case-Control Study from China.
AB - BACKGROUND: Myocarditis is an uncommon but serious manifestation of systemic
lupus erythematosus (SLE). This study aimed to investigate clinical
characteristics and outcomes of lupus myocarditis (LM) and to determine risk
factors of LM in hospitalized Chinese patients with SLE. METHODS: We conducted a
retrospective case-control study. A total of 25 patients with LM from 2001 to
2012 were enrolled as the study group, and 100 patients with SLE but without LM
were randomly pooled as the control group. Univariable analysis was performed
using Chi-square tests for categorical variables, and the Student's t-test or
Mann-Whitney U-test was performed for continuous variables according to the
normality. RESULTS: LM presented as the initial manifestation of SLE in 7
patients (28%) and occurred mostly at earlier stages compared to the controls
(20.88 +/- 35.73 vs. 44.08 +/- 61.56 months, P = 0.008). Twenty-one patients
(84%) experienced episodes of symptomatic heart failure. Echocardiography showed
that 23 patients (92%) had decreased left ventricular ejection fraction (<50%)
and all patients had wall motion abnormalities. A high SLE Disease Activity Index
was the independent risk factor in the development of LM (odds ratio = 1.322, P <
0.001). With aggressive immunosuppressive therapies, most patients achieved
satisfactory outcome. The in-hospital mortality was not significantly higher in
the LM group than in the controls (4% vs. 2%,P = 0.491). CONCLUSIONS: LM could
result in cardiac dysfunction and even sudden death. High SLE disease activity
might potentially predict the occurrence of LM at the early stage of SLE.
Characteristic echocardiographic findings could confirm the diagnosis of LM.
Early aggressive immunosuppressive therapy could improve the cardiac outcome of
LM.
PMID- 26415797
TI - Vagus Nerve Stimulation for Pediatric and Adult Patients with Pharmaco-resistant
Epilepsy.
AB - BACKGROUND: Over past two decades, vagus nerve stimulation (VNS) has been widely
used and reported to alleviate seizure frequency worldwide, however, so far, only
hundreds of patients with pharmaco-resistant epilepsy (PRE) have been treated
with VNS in mainland China. The study aimed to evaluate the effectiveness of VNS
for Chinese patients with PRE and compare its relationship with age cohort and
gender. METHODS: We retrospectively assessed the clinical outcome of 94 patients
with PRE, who were treated with VNS at Beijing Fengtai Hospital and Beijing
Tiantan Hospital between November 2008 and April 2014 from our database of 106
consecutive patients. The clinical data analysis was retrospectively examined.
RESULTS: Seizure frequency significantly decreased with VNS therapy after
intermittent stimulation of the vagus nerve. At last follow-up, we found McHugh
classifications of Class I in 33 patients (35.1%), Class II in 27 patients
(28.7%), Class III in 20 patients (21.3%), Class IV in 3 patients (3.2%), and
Class V in 11 patients (11.7%). Notably, 8 (8.5%) patients were seizure-free
while >=50% seizure frequency reduction occurred in as many as 60 patients
(63.8%). Furthermore, with regard to the modified Engel classification, 12
patients (12.8%) were classified as Class I, 11 patients (11.7%) were classified
as Class II, 37 patients (39.4%) were classified as Class III, 34 patients
(36.2%) were classified as Class IV. We also found that the factors of gender or
age are not associated with clinical outcome. CONCLUSIONS: This comparative study
confirmed that VNS is a safe, well-tolerated, and effective treatment for Chinese
PRE patients. VNS reduced the seizure frequency regardless of age or gender of
studied patients.
PMID- 26415796
TI - Spinal Cord Kinking in Thoracic Myelopathy Caused by Ossification of the
Ligamentum Flavum.
AB - BACKGROUND: Ossification of the ligamentum flavum (OLF) is being increasingly
recognized as a cause of thoracic myelopathy. This study was to describe a rare
clinical entity of spinal cord kinking (SK) in thoracic myelopathy secondary to
OLF. METHODS: The data of 95 patients with thoracic myelopathy secondary to OLF
were analyzed retrospectively. The incidence and location of SK were determined
using preoperative magnetic resonance imaging (MRI). The clinical presentation
and radiological characteristics in patients with SK were analyzed. Posterior en
bloc laminectomy with OLF was performed, and the surgical results were evaluated.
RESULTS: SK was found in seven patients (7.4%) based on preoperative MRI. The
patients included one male and six females with an average age of 55.6 years
(range, 48-64 years). Five patients presented with radiculomyelopathy and two
presented with typical thoracic myelopathy of spastic paraparesis. In all cases,
the kinking was located just above the end of the spinal cord where the conus
medullaris (CM) was compressed by the OLF. The degree of SK varied from mild to
severe. The tip of the CM was located between the upper third of T11 to the lower
third of L1, above the lower edge of L1. With an average follow-up of 30.4
months, the modified Japanese Orthopedic Association score significantly improved
from 5.7 +/- 1.8 preoperatively to 8.9 +/- 1.4 postoperatively (t = 12.05; P <
0.0001) with an improvement rate of 63.1 +/- 12.3%. CONCLUSIONS: SK is a rare
radiological phenomenon. It is typically located at the thoracolumbar junction,
where the CM is compressed by the OLF. Our findings indicate that these patients
may benefit from a posterior decompressive procedure.
PMID- 26415798
TI - The Surgical Treatment and Outcome of Nonmetastatic Extremity Osteosarcoma with
Pathological Fractures.
AB - BACKGROUND: Recent studies have suggested that the presence of a pathological
fracture does not impact on oncologic outcomes and the feasibility of limb
salvage surgery (LSS) in appropriately selected patients when combined with
neoadjuvant chemotherapy. These have largely been single institutional studies
with limited numbers. The Eastern Asian Musculoskeletal Oncology Group reviewed
the data from three large volume Asian orthopedic oncology centers to determine
whether the presence of a pathologic fracture affected outcomes in osteosarcoma
patients. METHODS: A retrospective review of the data was conducted. Ninety-five
cases of nonmetastatic extremity osteosarcoma with a pathological fracture and
887 cases without fracture treated during the same period were compared. RESULTS:
In the fracture group, the LSS rate was 62.1%, and the rate of amputation was
37.9%. In the nonfracture group, the LSS rate was 74.7%, and the amputation was
25.3%. In patients with a pathologic fracture, the rate of local recurrence for
LSS and amputation groups was 8.5% and 2.8%, respectively. In this group, the 5
year survival in the LSS group was 66% as against. 46.8% in the amputation group.
CONCLUSIONS: Our study suggests that surgically treated patients with pathologic
fractures in osteosarcoma have adequate local control and do not have a poorer
outcome compared to patients without a fracture. Though osteosarcoma with a
pathologic fracture is not a contraindication for limb salvage, appropriate case
selection is important when deciding local control options to ensure adequate
oncologic clearance.
PMID- 26415799
TI - Can Tracheostomy Improve Outcome and Lower Resource Utilization for Patients with
Prolonged Mechanical Ventilation?
AB - BACKGROUND: It is not clear whether the benefits of tracheostomy remain the same
in the population. This study aimed to better examine the effect of tracheostomy
on clinical outcome among prolonged ventilator patients. METHODS: Data were from
the medical claims data in Taiwan. A total of 3880 patients with ventilator use
for more than 14 days between 2005 and 2009 were identified. Among them, 645
patients with tracheostomy conducted within 30 days of ventilator use were
compared to 2715 patients without tracheostomy on death during hospitalization
and study period, and successful weaning and medical utilization during
hospitalization. Cox proportional hazards and linear regression models were used
to examine the associations between tracheostomy and the main outcomes. RESULTS:
The tracheostomy rate was 30%, and 55% of tracheostomies were performed within 30
days of mechanical ventilation. After adjustments, patients with tracheostomy
were at a lower risk of death during hospitalization (hazard ratio [HR] =0.51;
95% confidence interval [CI] =0.43-0.61) and 5-year observation (HR = 0.73; 95%
CI = 0.66-0.81), and a lower probability of successful weaning (HR = 0.88; 95% CI
= 0.79-0.99). Higher medical use was also observed in patients with tracheostomy.
CONCLUSIONS: The beneficial effect for tracheostomy observed in our data was the
reduction of death. However, patients with tracheostomy were less likely to wean
and more likely to consume medical resources.
PMID- 26415800
TI - Phosphoproteomics Analysis of Endometrium in Women with or without Endometriosis.
AB - BACKGROUND: The molecular mechanisms underlying the endometriosis are still not
completely understood. In order to test the hypothesis that the approaches in
phosphoproteomics might contribute to the identification of key biomarkers to
assess disease pathogenesis and drug targets, we carried out a phosphoproteomics
analysis of human endometrium. METHODS: A large-scale differential
phosphoproteome analysis, using peptide enrichment of titanium dioxide purify and
sequential elution from immobilized metal affinity chromatography with linear
trap quadrupole-tandem mass spectrometry, was performed in endometrium tissues
from 8 women with or without endometriosis. RESULTS: The phosphorylation
profiling of endometrium from endometriosis patients had been obtained, and found
that identified 516 proteins were modified at phosphorylation level during
endometriosis. Gene ontology annotation analysis showed that these proteins were
enriched in cellular processes of binding and catalytic activity. Further pathway
analysis showed that ribosome pathway and focal adhesion pathway were the top two
pathways, which might be deregulated during the development of endometriosis.
CONCLUSIONS: That large-scale phosphoproteome quantification has been
successfully identified in endometrium tissues of women with or without
endometriosis will provide new insights to understand the molecular mechanisms of
the development of endometriosis.
PMID- 26415801
TI - Direct-acting Antiviral Agents Resistance-associated Polymorphisms in Chinese
Treatment-naive Patients Infected with Genotype 1b Hepatitis C Virus.
AB - BACKGROUND: It has been reported that several baseline polymorphisms of direct
acting antivirals (DAAs) agents resistance-associated variants (RAVs) would
affect the treatment outcomes of patients chronically infected with hepatitis C
virus (CHC). The aim of this study is to investigate the prevalence of DAAs RAVs
in treatment-naIve GT1b CHC patients. METHODS: Direct sequencing and ultra-deep
sequencing of the HCV NS3, NS5A, and NS5B gene were performed in baseline serum
samples of treatment-naIve patients infected with genotype 1b hepatitis C virus
(HCVs). RESULTS: One hundred and sixty CHC patients were studied. Complete
sequence information was obtained for 145 patients (NS3), 148 patients (NS5A),
and 137 patients (NS5B). Treatment-failure associated variants of DAAs were
detected: 56.6% (82/145) of the patients presented S122G for simeprevir (NS3
protease inhibitor); 10.1% (14/148) of the patients presented Y93H for
daclatasvir and ledipasvir (NS5A protein inhibitors); 94.2% (129/137) of the
patients presented C316N for sofosbuvir (NS5B polymerase inhibitor). Nearly, all
of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct
sequencing. CONCLUSIONS: The majority of genotype 1b CHC patients in China
present a virus population carrying HCV DAAs RAVs. Pretreatment sequencing of HCV
genome might need to be performed when patients infected with GT1b HCV receiving
DAAs-containing regimens in China. Population sequencing would be quite
quantified for the work.
PMID- 26415802
TI - Prognostic Significance of MiR-34a Expression in Patients with Gastric Cancer
after Radical Gastrectomy.
AB - BACKGROUND: MiR-34a dysregulation has been implicated in tumorigenesis and
progression of gastric cancer, but its role in prognosis of patients with gastric
cancer remains unknown. The aim of this study was to investigate the expression
and prognostic significance of miR-34a in gastric cancer patients after radical
gastrectomy. METHODS: Quantitative real-time polymerase chain reaction was
performed to detect the expression of miR-34a in human gastric cancer cell lines
and tissues in 76 patients with gastric adenocarcinoma from China. Results are
assessed for association with clinical features and overall survival (OS) using
Kaplan-Meier analysis. Prognostic values of miR-34a expression and clinical
outcomes were evaluated by Cox regression analysis. A molecular prognostic
stratification scheme incorporating miR-34a expression was determined using
receiver operating characteristic analysis. RESULTS: The results show that the
expression level of miR-34a was decreased in human gastric cancer cell lines and
tissues, and down-regulated expression of miR-34a was associated with Lauren
classification (P = 0.034). Decreased miR-34a expression in gastric cancer
tissues was positively correlated with poor OS of gastric cancer patients (P =
0.013). Further multivariate Cox regression analysis suggested that miR-34a
expression was an independent prognostic indicator for gastric cancer (P =
0.027). Applying the prognostic value of miR-34a expression to tumor node
metastasis (TNM) stage system showed a better prognostic value in patients with
gastric cancer than miR-34a expression (P = 0.0435) or TNM stage (P = 0.0249)
alone. CONCLUSION: The results reinforce the critical role for the down-regulated
miR-34a expression in gastric cancer and suggest that miR-34a could be a
prognostic indicator for this disease.
PMID- 26415803
TI - Inhibition of Alveolar Macrophage Pyroptosis Reduces Lipopolysaccharide-induced
Acute Lung Injury in Mice.
AB - BACKGROUND: Pyroptosis is the term for caspase-1-dependent cell death associated
with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis
in the pathogenesis of the acute lung injury and acute respiratory distress
syndrome (ALI/ARDS) remains unclear. METHODS: C57BL/6 wild-type mice were
assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl-
alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp
fluoromethylketone groups. Mice were given intraperitoneal (IP) injections of
LPS. Drugs were IP injected 1 h before LPS administration. Mice were sacrificed
16 h after LPS administration, and AMs were isolated. Western blot analysis for
active caspase-1 and cleaved caspase-3, evaluation of lung injury and a cytokine
release analysis were performed. AMs were treated with LPS and adenosine
triphosphate (ATP); caspase-1-dependent cell death was evaluated using flow
cytometry; the apoptosis-associated speck-like protein containing a caspase
recruitment domain (ASC) pyroptosomes were examined by immunofluorescence.
RESULTS: The expression of activated caspase-1 in AMs was enhanced following LPS
challenge compared with the sham group. In the ex vivo study, the caspase
1/propidium iodide-positive cells, caspase-1 specks and ASC pyroptosomes were up
regulated in AMs following LPS/ATP stimulation. The specific caspase-1 inhibitor
Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death. Ac
YVAD-CMK also reduced the lung injury, pulmonary edema and total protein in
bronchoalveolar lavage fluid (BALF). In addition, Ac-YVAD-CMK significantly
inhibited interleukin-alpha2 (IL-1alpha2) release both in serum and BALF and
reduced the levels of IL-18, tumor necrosis factor-alpha+/- (TNF-alpha+/-), High
Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS. CONCLUSIONS:
This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has
demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury.
These preliminary findings may form the basis for further studies to evaluate
this pathway as a target for prevention or reduction of ALI/ARDS.
PMID- 26415804
TI - Improved Survival and Neurological Outcomes after Cardiopulmonary Resuscitation
in Toll-like Receptor 4-mutant Mice.
AB - BACKGROUND: Toll-like receptor 4 (TLR4) is a crucial receptor in the innate
immune system and noninfectious immune responses. It has been reported that TLR4
participates in the pathological course of ischemia/reperfusion (I/R) injury.
However, the role of TLR4 in the process of I/R injury after cardiac arrest (CA)
and cardiopulmonary resuscitation (CPR) is still unknown. In this study, we
investigated the effects of TLR4 mutation on survival and neurological outcome in
a mouse model of CA/CPR. METHODS: A model of potassium-induced CA was performed
on TLR4-mutant mice (C3H/HeJ) and wild-type mice (C3H/HeN). After 3 min of
untreated CA, resuscitation was attempted with chest compression, ventilation,
and intravenous epinephrine. Behavioral tests were performed on mice on day 3
after CPR. The morphological changes in hippocampal neurons were assessed by
light and electron microscopy. Expressions of TLR4 and intercellular adhesion
molecule-1 (ICAM-1) were detected by Western blot. Levels of tumor necrosis
factor-alpha (TNF-alpha) and myeloperoxidase (MPO) were measured with enzyme
linked immunosorbent assay (ELISA). RESULTS: On day 3 after resuscitation the
overall mortality was 33.33% in C3H/HeJ group compared with 53.33% in C3H/HeN
group (P < 0.05). And there was much higher central tendency in C3H/HeJ group
than C3H/HeN group during open field test (P < 0.05). Meanwhile, the percentage
of nonviable neurons was 21.16% in C3H/HeJ group compared with 53.11% in C3H/HeN
group (P < 0.05). And there were significantly lower levels of hippocampal TNF
alpha and MPO in C3H/HeJ mice (TNF-alpha: 6.85+/-1.19 ng/mL, MPO: 0.33+/-0.11
U/g) than C3H/HeN mice (TNF-alpha: 11.36+/-2.12 ng/mL, MPO: 0.54+/-0.17 U/g) (all
P < 0.01). CPR also significantly increased the expressions of TLR4 and ICAM-1 in
C3H/HeN group. However, the expression of ICAM-1 was much lower in C3H/HeJ group
than in C3H/HeN group after CPR (P < 0.01). CONCLUSION: TLR4 signaling is
involved in brain damage and in inflammation triggered by CA/CPR.
PMID- 26415805
TI - Neuroprotective Effect of Compound Anisodine in a Mouse Model with Chronic Ocular
Hypertension.
AB - BACKGROUND: Compound anisodine (CA) is a compound preparation made from
hydrobromide anisodine and procaine hydrochloride. The former is an M-choline
receptor blocker with the function of regulating the vegetative nervous system,
improving microcirculation, and so on. The latter is an antioxidant with the
activities of neuroprotection. This study aimed to investigate the potential
neuroprotection of CA, which affects the degeneration of the retinal ganglion
cells (RGCs) in an animal model with chronic ocular hypertension. METHODS: Female
C57BL/6J mice (n = 24) were divided randomly into four groups: normal control
group without any treatment (Group A, n = 6); CA control group with feeding the
CA solution (Group B, n = 6); microbeads (MBs) control group with injecting MB
into the anterior chamber (Group C, n = 6); CA study group with MB injection and
with feeding the CA solution (Group D, n = 6). Intraocular pressure (IOP) was
measured every 3 days after MB injection. At the 21st day, neurons were
retrograde-labeled by Fluoro-Gold (FG). Animals were sacrificed on the 27th day.
Retinal flat mounts were stained immunohistologically by alpha2-III-tubulin. FG
retrograde-labeled RGCs, alpha2-III-tubulin-positive RGCs, and alpha2-III-tubulin
positive nerve fibers were quantified. RESULTS: Mice of Groups C and D expressed
the incidence of consistent IOP elevation, which is above the IOP level of Group
A with the normal one. There is no significant difference in IOP between Groups A
and B (P > 0.05). On the 27th day, there were distinct loss in stained RGCs and
nerve fibers from Groups C and D compared with Group A (allP < 0.001). The
quantity was significantly higher in Group D as compared to Group C (allP <
0.001) but lower than Group A (allP > 0.001). There was no significant difference
in the quantity of RGCs and nerve fibers between Groups A and B (allP > 0.05).
CONCLUSIONS: These findings suggest that CA plays an importantly neuroprotective
role on RGCs in a mouse model with chronic ocular hypertension.
PMID- 26415806
TI - Salvianolic Acid B Down-regulates Matrix Metalloproteinase-9 Activity and
Expression in Tumor Necrosis Factor-alpha-induced Human Coronary Artery
Endothelial Cells.
AB - BACKGROUND: Salvianolic acid B (Sal B) is a bioactive water-soluble compound of
Salviae miltiorrhizae, a traditional herbal medicine that has been used
clinically for the treatment of cardiovascular diseases. This study sought to
evaluate the effect of Sal B on matrix metalloproteinase-9 (MMP-9) and on the
underlying mechanisms in tumor necrosis factor-alpha+/- (TNF-alpha+/-)-activated
human coronary artery endothelial cells (HCAECs), a cell model of Kawasaki
disease. METHODS: HCAECs were pretreated with 1-10 alphaMUmol/L of Sal B, and
then stimulated by TNF-alpha+/- at different time points. The protein expression
and activity of MMP-9 were determined by Western blot assay and gelatin zymogram
assay, respectively. Nuclear factor-kappaB (NF-kappaB) activation was detected
with immunofluorescence, electrophoretic mobility shift assay, and Western blot
assay. Protein expression levels of mitogen-activated protein kinase (c-Jun N
terminal kinase [JNK], extra-cellular signal-regulated kinase [ERK], and p38)
were determined by Western blot assay. RESULTS: After HCAECs were exposed to TNF
alpha+/-, 1-10 alphaMUmol/L Sal B significantly inhibited TNF-alpha+/--induced
MMP-9 expression and activity. Furthermore, Sal B significantly decreased
IkappaBalpha+/- phosphorylation and p65 nuclear translocation in HCAECs
stimulated with TNF-alpha+/- for 30 min. In addition, Sal B decreased the
phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-alpha+/- for
10 min. CONCLUSIONS: The data suggested that Sal B suppressed TNF-alpha+/-
induced MMP-9 expression and activity by blocking the activation of NF-kappaB,
JNK, and ERK1/2 signaling pathways.
PMID- 26415807
TI - Mass Casualty Incident Primary Triage Methods in China.
AB - OBJECTIVE: To evaluate the technical characteristics and application of mass
casualty incident (MCI) primary triage (PT) methods applied in China. DATA
SOURCES: Chinese literature was searched by Chinese Academic Journal Network
Publishing Database (founded in June 2014). The English literature was searched
by PubMed (MEDLINE) (1950 to June 2014). We also searched Official Websites of
Chinese Central Government's (http://www.gov.cn/), National Health and Family
Planning Commission of China (http://www.nhfpc.gov.cn/), and China Earthquake
Information (http://www.csi.ac.cn/). STUDY SELECTION: We included studies
associated with mass casualty events related to China, the PT applied in China,
guidelines and standards, and application and development of the carding PT
method in China. RESULTS: From 3976 potentially relevant articles, 22 met the
inclusion criteria, 20 Chinese, and 2 English. These articles included 13 case
reports, 3 retrospective analyses of MCI, two methods introductions, three
national or sectoral criteria, and one simulated field testing and validation.
There were a total of 19 kinds of MCI PT methods that have been reported in China
from 1950 to 2014. In addition, there were 15 kinds of PT methods reported in the
literature from the instance of the application. CONCLUSIONS: The national and
sectoral current triage criteria are developed mainly for earthquake relief.
Classification is not clear. Vague criteria (especially between moderate and
severe injuries) operability are not practical. There are no triage methods and
research for children and special populations. There is no data and evidence
supported triage method. We should revise our existing classification and
criteria so it is clearer and easier to be grasped in order to build a real,
practical, and efficient PT method.
PMID- 26415808
TI - Application of Lung Ultrasonography in the Diagnosis of Childhood Lung Diseases.
AB - In this paper, we focus on the characteristics of LUS in diagnosing childhood
pulmonary disease. LUS is convenient, noninvasive, and free of radiation. It
helps in the differentiation of lung diseases. Therefore, LUS has the potential
to become a reference instrument for bedside dynamic respiratory monitoring. We
hope that this review will help clinicians become acquainted with LUS and will
accelerate the extensive application of LUS in children.
PMID- 26415809
TI - Diced Costal Cartilage for Augmentation Rhinoplasty.
PMID- 26415810
TI - Clinical Features and Prognosis of Ocular Myasthenia Gravis Patients with
Different Phenotypes.
PMID- 26415811
TI - A Rare Case of Ovarian Cancer Presenting with Paraneoplastic Cerebellar
Degeneration and Limbic Encephalitis.
PMID- 26415812
TI - Myocyte Enhancer Factor-2A Gene Mutation and Coronary Artery Disease.
AB - BACKGROUND: Premature ventricular contractions (PVCs) are common in the general
population, and frequent PVCs may result in the poor quality of life or even the
damage of cardiac function. We examined the efficacy and safety of a traditional
Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a
relatively large Chinese cohort. METHODS: We performed a randomized, double
blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200
eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin
Keli or the placebo for 4 weeks. The primary and secondary endpoint was the
change of PVC numbers and PVC-related symptoms after a 4-week treatment compared
with baseline, respectively. In addition, vital signs, laboratory values, and
electrocardiographic parameters were assessed in a safety analysis. RESULTS: At
the initial evaluation, no significant differences in the baseline
characteristics were observed between the Wenxin Keli group and the placebo
group. A smaller number of PVCs was observed after the 4-week treatment than at
baseline, in both the Wenxin Keli group (5686 +/- 5940 vs. 15,138 +/- 7597
beats/d, P < 0.001) and the placebo group (10,592 +/- 8009 vs. 14,529 +/- 5929
beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantly
greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In
a full analysis set, patients in the Wenxin Keli group exhibited significantly
higher total effective responses in the reduction of PVCs compared to those in
the placebo group (83.8% vs. 43.5%,P < 0.001). The per-protocol analysis yielded
similar results (83.0% vs. 39.3%,P < 0.001). Treatment with Wenxin Keli also
demonstrated superior performance compared to the placebo with respect to PVC
related symptoms. No severe adverse effects attributable to Wenxin Keli were
reported. CONCLUSIONS: Wenxin Keli treatment effectively reduced the overall
number of PVCs and alleviated PVC-related symptoms in patients without structural
heart diseases and had no severe side effects.
PMID- 26415813
TI - Acute Myocardial Infarction Due to Stent Thrombosis After Administration of
Intravenous Epinephrine for Anaphylaxis.
PMID- 26415814
TI - Paget-Schroetter Syndrome.
PMID- 26415815
TI - Endobronchial Solitary Fibrous Tumor: Imaging and Bronchoscopic Findings.
PMID- 26415816
TI - Adenoma of the Ciliary Pigment Epithelium with Diffuse Iris Pigment Dispersion.
PMID- 26415817
TI - Development of a validated questionnaire to measure the self-perceived competence
of primary health professionals in providing nutrition care to patients with
chronic disease.
AB - BACKGROUND: Nutrition is an important aspect of chronic disease prevention and
management by primary health professionals, including GPs, dietitians, practice
nurses, diabetes educators and exercise professionals. In order to better
understand how to improve the delivery of nutrition care, it is important to have
valid and reliable tools to measure self-perceived competence. OBJECTIVE: This
study aimed to develop a valid, structured, questionnaire that measures the self
perceived competence of primary health professionals to provide nutrition care to
patients with chronic disease. METHODS: The development of the questionnaire was
carried out in four stages (1): preparation of scope and structure, through a
literature review and consultation with an expert reference group (2);
development of questionnaire items, which were refined through feedback from the
reference group and 18 primary health professionals (3); investigation of
internal consistency and concurrent validity through a pilot study on 118 primary
health professionals (4) and investigation of test-retest reliability through a
pilot study on 33 primary health professionals who completed the questionnaire
twice, 2-3 weeks apart. RESULTS: Stages 1 and 2 resulted in four constructs and
35 questions in the questionnaire. Stage 3 confirmed internal consistency, with
Cronbach's alpha ranging from 0.88 to 0.98 for each construct and 0.98 for all
items combined. Dietitians scored significantly higher than speech pathologists
(P < 0.05) in each construct, confirming concurrent validity. Stage 4 confirmed
test-retest reliability, with correlation coefficients ranging from 0.89 to 0.94
for each construct and 0.95 for all items combined. CONCLUSION: The NUTrition
COMPetence (NUTCOMP) questionnaire is a valid, reliable and suitable tool that
can be used to directly inform professional development and identify
opportunities to support safe and effective practice.
PMID- 26415819
TI - Xanthine oxidase injurious response in acute joint injury.
AB - BACKGROUND: While acute trauma is a major cause of osteoarthritis, its etiology
is poorly understood. We sought to determine whether xanthine oxidase (XO), a
major producer of reactive oxygen species, plays a role in the early events of
acute joint injury. METHODS: We analyzed synovial fluid from 23 subjects with
recent severe acute knee injury. As a control we evaluated SF from 23 individuals
with no or minimal knee osteoarthritis. We measured XO activity, reactive
oxygen+reactive nitrogen species (ROS+RNS), protein oxidative damage (carbonyl),
the type II collagen synthesis marker procollagen II c-propeptide (CPII) and the
type II collagen degradation marker collagen type II telopeptide (CTx-II). We
also measured the proinflammatory cytokine IL-6. RESULTS: XO and ROS+RNS were
higher (p=0.02 and p=0.001 respectively) in acute injury than control and were
strongly positively associated (r=0.62, p=0.004). Carbonyl was higher in acute
injury than control (p=0.0002) and was positively correlated with XO (r=0.68,
p=0.0007) as well as with ROS+RNS (r=0.71, p=0.004). CPII was higher in acute
injury than control (p<0.0001) and was negatively correlated with XO (r=-0.49,
p=0.017). While CTxII was not significantly higher in acute injury than control,
it was positively correlated with CPII (r=0.71, p=0.0002). IL-6 was higher in
acute injury than control (p<0.0001). CONCLUSIONS: These results are consistent
with a potentially injurious effect of XO activity in acute joint injury
characterized by excess free radical production and oxidative damage. These
effects are associated with an inhibition of type II collagen production that may
impede the ability of the injured joint to repair.
PMID- 26415820
TI - MicroRNA in prostate cancer.
AB - In the United States of America male prostate cancer (PCa) is the most dominant
malignancy and the second highest cause of cancer-related mortality risk compared
to lung and colon cancers. MicroRNAs (miRNAs) are a class of endogenously
expressed small, non-coding, single-stranded RNA which function as regulators of
gene expression. They influence various physiological and pathophysiological
processes. In this review, we focus on the regulation of miRNAs in prostate
cancer and their mechanisms which contribute to prostate carcinogenesis. The
relation of miRNAs with androgen signaling is highlighted and the prospects of
miRNAs for clinical therapies are discussed.
PMID- 26415821
TI - A novel quantitative evaluation method for quality control results.
AB - BACKGROUND: Quality control (QC) procedures using stable control materials are
important for preventing systematic errors (SEs). While the current QC methods
assess QC results semi-quantitatively, we designed a novel quantitative QC
procedure (QQCP). METHODS: QC results were expressed as Z-scores to analyze
results quantitatively. The decision values were accumulated up to 30, with three
decision values per run, and were compared to rejection criteria at each run. The
probability for false rejection (Pfr) and error detection (Ped) for the QQCP and
Westgard multirule methods were estimated using simulated QC data with SEs
ranging from 0 to 3 standard deviations (SDs). RESULTS: The Pfr of the QQCP was
3.4% at the 10th run. When 2 QC materials with the same SEs (0.5 SD and 1.0 SD)
were used, the Peds were 36.1% and 95.7% at run 10, respectively. When the SE of
each material was greater than 1.5 SDs, the Ped reached 100% at run 10. The QQCP
could detect more than 99% of errors in the 6th, 4th, 3rd, and 2nd runs for 2 QC
results with 1.5, 2.0, 2.5, and 3.0 SD SEs, respectively. CONCLUSION: The QQCP
exhibited a Ped value up to 3.3-fold higher than the Westgard method.
Implementation of the QQCP would satisfy the high quality goals derived from
biological variations.
PMID- 26415822
TI - Interventions to increase engagement with rehabilitation in adults with acquired
brain injury: A systematic review.
AB - Rehabilitation in adults with acquired brain injury is often hampered by a lack
of client engagement with the rehabilitation process, leading to frustration,
withdrawal of services and poorer recovery. Motivation, apathy and awareness are
potential mechanisms underlying engagement, but few studies have suggested
potential intervention techniques. A systematic review of the literature was
carried out to identify and evaluate interventions designed to increase
rehabilitation engagement in adults with acquired brain injury. Database searches
used the following terms: rehabilitation, brain injury, and
compliance/engagement/adherence in PsychInfo, Medline, Cinahl, Embase, AMED, Web
of Knowledge, PsycBite, Cochrane clinical trials, and clinicaltrials.org. Hand
searches were conducted of reference lists and relevant journals. Fifteen studies
were included in the review. Intervention techniques fell into two broad
categories: behavioural modification techniques and cognitive/meta-cognitive
skills. Contingent reward techniques were most effective at increasing adherence
and compliance, while interventions enabling clients' active participation in
rehabilitation appeared to increase engagement and motivation. The review
highlighted methodological and measurement inconsistencies in the field and
suggested that interventions should be tailored to clients' abilities and
circumstances.
PMID- 26415818
TI - Differential involvement of cortical and cerebellar areas using dominant and
nondominant hands: An FMRI study.
AB - Motor fMRI studies, comparing dominant (DH) and nondominant (NDH) hand
activations have reported mixed findings, especially for the extent of
ipsilateral (IL) activations and their relationship with task complexity. To
date, no study has directly compared DH and NDH activations using an event
related visually guided dynamic power-grip paradigm with parametric (three)
forces (GF) in healthy right-handed subjects. We implemented a hierarchical
statistical approach aimed to: (i) identify the main effect networks engaged when
using either hand; (ii) characterise DH/NDH responses at different GFs; (iii)
assess contralateral (CL)/IL-specific and hemisphere-specific activations. Beyond
confirming previously reported results, this study demonstrated that increasing
GF has an effect on motor response that is contextualised also by the use of DH
or NDH. Linear analysis revealed increased activations in sensorimotor areas,
with additional increased recruitments of subcortical and cerebellar areas when
using the NDH. When looking at CL/IL-specific activations, CL sensorimotor areas
and IL cerebellum were activated with both hands. When performing the task with
the NDH, several areas were also recruited including the CL cerebellum. Finally,
there were hand-side-independent activations of nonmotor-specific areas in the
right and left hemispheres, with the right hemisphere being involved more
extensively in sensori-motor integration through associative areas while the left
hemisphere showing greater activation at higher GF. This study shows that the
functional networks subtending DH/NDH power-grip visuomotor functions are
qualitatively and quantitatively distinct and this should be taken into
consideration when performing fMRI studies, particularly when planning
interventions in patients with specific impairments.
PMID- 26415824
TI - Interobserver agreement in assessment of polycystic ovarian morphology using
pattern recognition.
PMID- 26415823
TI - beta-Lapachone and Paclitaxel Combination Micelles with Improved Drug
Encapsulation and Therapeutic Synergy as Novel Nanotherapeutics for NQO1-Targeted
Cancer Therapy.
AB - beta-Lapachone (LPC) is a novel cytotoxic agent that is bioactivated by NADP(H):
quinone oxidoreductase 1 (NQO1), an enzyme elevated in a variety of tumors, such
as non-small cell lung cancer (NSCLC), pancreatic cancer, liver cancer, and
breast cancer. Despite its unique mechanism of action, its clinical evaluation
has been largely hindered by low water solubility, short blood half-life, and
narrow therapeutic window. Although encapsulation into poly(ethylene glycol)-b
poly(D,L-lactic acid) (PEG-PLA) micelles could modestly improve its solubility
and prolong its half-life, the extremely fast intrinsic crystallization tendency
of LPC prevents drug loading higher than ~2 wt %. The physical stability of the
LPC-loaded micelles is also far from satisfactory for further development. In
this study, we demonstrate that paclitaxel (PTX), a front-line drug for many
cancers, can provide two functions when coencapsulated together with LPC in the
PEG-PLA micelles; first, as a strong crystallization inhibitor for LPC, thus to
significantly increase the LPC encapsulation efficiency in the micelle from 11.7
+/- 2.4% to 100.7 +/- 2.2%. The total drug loading efficiency of both PTX and LPC
in the combination polymeric micelle reached 100.3 +/- 3.0%, and the drug loading
density reached 33.2 +/- 1.0%. Second, the combination of LPC/PTX demonstrates
strong synergistic cytotoxicity effect against the NQO1 overexpressing cancer
cells, including A549 NSCLC cells, and several pancreatic cancer cells
(combination index <1). In vitro drug release study showed that LPC was released
faster than PTX either in phosphate-buffered saline (PH = 7.4) or in 1 M sodium
salicylate, which agrees with the desired dosing sequence of the two drugs to
exert synergistic pharmacologic effect at different cell checkpoints. The PEG-PLA
micelles coloaded with LPC and PTX offer a novel nanotherapeutic, with high drug
loading, sufficient physical stability, and biological synergy to increase drug
delivery efficiency and optimize the therapeutic window for NOQ1-targeted therapy
of cancer.
PMID- 26415826
TI - Femtosecond laser controlled wettability of solid surfaces.
AB - Femtosecond laser microfabrication is emerging as a hot tool for controlling the
wettability of solid surfaces. This paper introduces four typical aspects of
femtosecond laser induced special wettability: superhydrophobicity, underwater
superoleophobicity, anisotropic wettability, and smart wettability. The static
properties are characterized by the contact angle measurement, while the dynamic
features are investigated by the sliding behavior of a liquid droplet. Using
different materials and machining methods results in different rough
microstructures, patterns, and even chemistry on the solid substrates. So,
various beautiful wettabilities can be realized because wettability is mainly
dependent on the surface topography and chemical composition. The distinctions of
the underlying formation mechanism of these wettabilities are also described in
detail.
PMID- 26415825
TI - The role of sensory modality in prepulse inhibition: An ontogenetic study.
AB - Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, are
observed in neurodevelopmental and neuropsychiatric disorders. Despite the large
PPI literature, the majority of studies characteristically employ tests with one
interstimulus interval (ISI), of one modality, at one age. In the context of the
auditory startle response (ASR), the present study examined (1) the profile for
the ontogeny of PPI through adulthood in Long-Evans hooded rats with a reasonably
comprehensive ISI function, (2) whether the ontogenetic profile for PPI is
sensitive to modality of the prepulse stimulus, as a within-session variable, and
(3) whether the maturation of PPI differs for males and females. Despite the
basic effect of more pronounced PPI in adult relative to preweanling animals,
each sensory modality displayed a unique ontogenetic profile for PPI, without any
compelling evidence for major differences between males and females, in
accordance with the known temporal course of peripheral and central maturational
profiles of sensory systems in the rat. The context for assessing auditory PPI
(auditory and tactile vs. auditory and visual prepulses) influenced the overall
startle response, i.e., a shift in the height of the entire profile, but did not
significantly impact the auditory PPI profile per se. The translational relevance
of preclinical sensorimotor assessments to patients with neurodevelopmental
and/or neuropsychiatric disorders depends partly on an understanding of the
ontogeny of sensorimotor gating in different sensory systems, and can be
strengthened with the use of a reasonably comprehensive number of ISIs to provide
relatively precise and defined response functions.
PMID- 26415827
TI - Hydrometallurgical Recovery of Metals from Large Printed Circuit Board Pieces.
AB - The recovery of precious metals from waste printed circuit boards (PCBs) is an
effective recycling process. This paper presents a promising hydrometallurgical
process to recover precious metals from waste PCBs. To simplify the metal
leaching process, large pieces of PCBs were used instead of a pulverized sample.
The chemical coating present on the PCBs was removed by sodium hydroxide (NaOH)
treatment prior to the hydrometallurgical treatment. Among the leaching reagents
examined, hydrochloric acid (HCl) showed great potential for the recovery of
metals. The HCl-mediated leaching of waste PCBs was investigated over a range of
conditions. Increasing the acid concentration decreased the time required for
complete metal recovery. The shaking speed showed a pronounced positive effect on
metal recovery, but the temperature showed an insignificant effect. The results
showed that 1 M HCl recovered all of the metals from 4 cm * 4 cm PCBs at room
temperature and 150 rpm shaking speed in 22 h.
PMID- 26415828
TI - Standalone medical device software: The evolving regulatory framework.
AB - The paper provides an introduction to the regulatory landscape affecting a
particular category of medical technology, namely standalone software-sometimes
referred to as 'software as a medical device'. To aid the reader's comprehension
of an often complex area, six case studies are outlined and discussed before the
paper continues to provide detail of how software with a medical purpose in its
own right can potentially be classified as a medical device. The reader is
provided an appreciation of how to go about classifying such software and
references to support the developer new to the field in locating detailed
regulatory support documents and contact points for advice.
PMID- 26415829
TI - Mannan-decorated thiolated Eudragit microspheres for targeting antigen presenting
cells via nasal vaccination.
AB - Mucosal vaccination of protein as an antigen requires appropriate delivery or
adjuvant systems to deliver antigen to mucosal immune cells efficiently and
generate valid immune responses. For successful nasal immunization, the obstacles
imposed by the normal process of mucociliary clearance which limits residence
time of applied antigens and low antigen delivery to antigen presenting cells
(APCs) in nasal associated lymphoid tissue (NALT) need to be overcome for the
efficient vaccination. Here, we prepared mucoadhesive and mannan-decorated
thiolated Eudragit microspheres (Man-TEM) as a nasal vaccine carrier to overcome
the limitations. Mucoadhesive thiolated Eudragit (TE) were decorated with mannan
for targeting mannose receptors (MR) in antigen presenting cells (APCs) to obtain
efficient immune responses. The potential adjuvant ability of Man-TEM for
intranasal immunization was confirmed by in vitro and in vivo experiments. In
mechanistic study using APCs in vitro, we obtained that Man-TEM enhanced the
receptor-mediated endocytosis by stimulating the MR receptors of APCs. The nasal
vaccination of OVA-loaded Man-TEM in mice showed higher levels of serum IgG and
mucosal sIgA than the soluble OVA group due to the specific recognition of MR of
APCs by the mannan in the Man-TEM. These results suggest that mucoadhesive and
Man-TEM may be a promising candidate for nasal vaccine delivery system to elicit
systemic and mucosal immunity.
PMID- 26415830
TI - Encapsulation in a rapid-release liposomal formulation enhances the anti-tumor
efficacy of pemetrexed in a murine solid mesothelioma-xenograft model.
AB - We recently developed a PEG-coated liposome encapsulating the anti-folate drug
pemetrexed (PMX). Such liposomal formulations have shown potent cytotoxic effects
against malignant pleural mesothelioma (MPM) cells in vitro. In the present
study, we investigated the pharmacokinetics, bio-distribution and in vivo anti
tumor efficacy of two liposomal PMX formulations with different drug release
rates in a murine mesothelioma-xenograft model. Liposomes with different PMX
release rates were prepared via manipulating liposomal membrane fluidity through
incorporating either a solid-phase (HSPC) or a fluid-phase (POPC) phospholipid.
Both liposomal PMX formulations showed prolonged plasma pharmacokinetics and were
accumulated to a similar extent in tumors and other tissues, presumably, due to
surface modification with polyethylene glycol (PEG). In a murine mesothelioma
xenograft model, interestingly, PMX encapsulated in a fast-release POPC liposome
produced superior tumor growth suppression compared with either free PMX or PMX
encapsulated in a slow-release HSPC liposome. Such in vivo anti-tumor efficacy
was accomplished mainly by a potent induction of apoptosis within tumor tissue by
the released PMX from POPC liposomes. Our results clearly emphasize the
therapeutic efficacy of liposomal PMX over free PMX in conquering aggressive
solid tumors such as malignant mesothelioma. A guarantee of the targeted delivery
of PMX to tumor cells helps overcome some of the major shortcomings encountered
with the use of free PMX.
PMID- 26415831
TI - Family members' needs and experiences of driving disruption due to health
conditions or ageing.
AB - PURPOSE: Family members often assume the caregiving role and provide practical
assistance and emotional support when an individual is experiencing driving
disruption due to health conditions or ageing. The purpose of this study was to
understand the experiences, viewpoints and needs of family members with regards
to an individual undergoing driving disruption across various population groups.
METHOD: A scoping review was conducted through searching across six databases and
hand searching articles published from 1985 to 2013. Findings from the articles
specific to the aims of the review were extracted and summarised into common
topics. RESULTS: Twenty-seven articles were included; dementia or cognitive
impairment (16 articles), older adults (8 articles) and brain injury (3
articles). The most common topic raised was related to decisions and consequences
for the individual. Other concerns were related to family members' occupational
role changes, emotional and communication issues and support needs of family
members and their recommendations for services. CONCLUSIONS: This review revealed
the impact of driving disruption on family members but research is limited,
especially in the area of brain injury. The majority of articles did not set out
to explore family members' experiences and needs and this highlights an area that
requires critical attention. IMPLICATIONS FOR REHABILITATION: Health
professionals should be aware of the potential impact of driving disruption on
family members. Family members frequently raise concerns regarding the decisions
and consequences for their relative, but also bring up personal concerns such as
changes to their own occupational roles and the communication and emotional
issues they face during driving disruption. Unique challenges arise between
family members of individuals of different health conditions, thus highlighting
the importance of family caregiving research in various population groups.
PMID- 26415832
TI - Posttranscriptional silencing of the lncRNA MALAT1 by miR-217 inhibits the
epithelial-mesenchymal transition via enhancer of zeste homolog 2 in the
malignant transformation of HBE cells induced by cigarette smoke extract.
AB - Lung cancer is regarded as the leading cause of cancer-related deaths, and
cigarette smoking is one of the strongest risk factors for the development of
lung cancer. However, the mechanisms for cigarette smoke-induced lung
carcinogenesis remain unclear. The present study investigated the effects of an
miRNA (miR-217) on levels of an lncRNA (MALAT1) and examined the role of these
factors in the epithelial-mesenchymal transition (EMT) induced by cigarette smoke
extract (CSE) in human bronchial epithelial (HBE) cells. In these cells, CSE
caused decreases of miR-217 levels and increases in lncRNA MALAT1 levels. Over
expression of miR-217 with a mimic attenuated the CSE-induced increase of MALAT1
levels, and reduction of miR-217 levels by an inhibitor enhanced expression of
MALAT1. Moreover, the CSE-induced increase of MALAT1 expression was blocked by an
miR-217 mimic, indicating that miR-217 negatively regulates MALAT1 expression.
Knockdown of MALAT1 reversed CSE-induced increases of EZH2 (enhancer of zeste
homolog 2) and H3K27me3 levels. In addition to the alteration from epithelial to
spindle-like mesenchymal morphology, chronic exposure of HBE cells to CSE
increased the levels of EZH2, H3K27me3, vimentin, and N-cadherin and decreased E
cadherin levels, effects that were reversed by MALAT1 siRNA or EZH2 siRNA. The
results indicate that miR-217 regulation of EZH2/H3K27me3 via MALAT1 is involved
in CSE-induced EMT and malignant transformation of HBE cells. The
posttranscriptional silencing of MALAT1 by miR-217 provides a link, through EZH2,
between ncRNAs and the EMT and establishes a mechanism for CSE-induced lung
carcinogenesis.
PMID- 26415833
TI - Compound- and sex-specific effects on programming of energy and immune
homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153.
AB - Early life exposure to endocrine disrupting compounds has been linked to chronic
diseases later in life, like obesity and related metabolic disorders. We exposed
C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8
tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane
receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an
experimental design relevant for human exposure. Exposure occurred during
gestation and lactation via maternal feed to a wide dose range (TCDD: 10-10,000
pg/kg body weight/day; PCB 153: 0.09-1406 MUg/kg body weight/d). Then exposure
was ceased and offspring were followed up to 1 year of age. Metabolic parameters
like body weight, fat pad weights, glucose tolerance, endocrine serum profile,
and neurobehavioral and immunological parameters were determined. Body weight was
transiently affected by both compounds throughout the follow-up. TCDD-exposed
males showed decreased fat pad and spleen weights and an increase in IL-4
production of splenic immune cells. In contrast, females showed increased fat pad
weights and production of IFNgamma. PCB 153-exposed males showed an increase in
glucose, whereas females showed an increase in glucagon, a decrease in pancreas
weight, and an increase in thymus weight. In conclusion, early life exposure to
TCDD appears to affect programming of energy and immune homeostasis in offspring,
whereas the effects of perinatal PCB 153 were mainly on programming of glucose
homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower
bounds of the (two sided) 90%-confidence interval for the benchmark dose) for
both compounds are not lower than current tolerable daily intakes.
PMID- 26415834
TI - Redox cycling of endogenous copper by ferulic acid leads to cellular DNA breakage
and consequent cell death: A putative cancer chemotherapy mechanism.
AB - Ferulic acid (FA) is a plant polyphenol showing diverse therapeutic effects
against cancer, diabetes, cardiovascular and neurodegenerative diseases. FA is a
known antioxidant at lower concentrations, however at higher concentrations or in
the presence of metal ions such as copper, it may act as a pro-oxidant. It has
been reported that copper levels are significantly raised in different
malignancies. Cancer cells are under increased oxidative stress as compared to
normal cells. Certain therapeutic substances like polyphenols can further
increase this oxidative stress and kill cancer cells without affecting the
proliferation of normal cells. Through various in vitro experiments we have shown
that the pro-oxidant properties of FA are enhanced in the presence of copper.
Comet assay demonstrated the ability of FA to cause oxidative DNA breakage in
human peripheral lymphocytes which was ameliorated by specific copper-chelating
agent such as neocuproine and scavengers of ROS. This suggested the mobilization
of endogenous copper in ROS generation and consequent DNA damage. These results
were further validated through cytotoxicity experiments involving different cell
lines. Thus, we conclude that such a pro-oxidant mechanism involving endogenous
copper better explains the anticancer activities of FA. This would be an
alternate non-enzymatic, and copper-mediated pathway for the cytotoxic activities
of FA where it can selectively target cancer cells with elevated levels of copper
and ROS.
PMID- 26415835
TI - Synergy of multi-scale toughening and protective mechanisms at hierarchical
branch-stem interfaces.
AB - Biological materials possess a variety of artful interfaces whose size and
properties are adapted to their hierarchical levels and functional requirements.
Bone, nacre, and wood exhibit an impressive fracture resistance based mainly on
small crystallite size, interface organic adhesives and hierarchical
microstructure. Currently, little is known about mechanical concepts in
macroscopic biological interfaces like the branch-stem junction with estimated
10(14) instances on earth and sizes up to few meters. Here we demonstrate that
the crack growth in the upper region of the branch-stem interface of conifer
trees proceeds along a narrow predefined region of transversally loaded
tracheids, denoted as sacrificial tissue, which fail upon critical bending
moments on the branch. The specific arrangement of the tracheids allows
disconnecting the overloaded branch from the stem in a controlled way by
maintaining the stem integrity. The interface microstructure based on the sharply
adjusted cell orientation and cell helical angle secures a zig-zag crack
propagation path, mechanical interlock closing after the bending moment is
removed, crack gap bridging and self-repairing by resin deposition. The multi
scale synergetic concepts allows for a controllable crack growth between stiff
stem and flexible branch, as well as mechanical tree integrity, intact
physiological functions and recovery after the cracking.
PMID- 26415836
TI - Benzodiazepine Prescribing in Older Adults in U.S. Ambulatory Clinics and
Emergency Departments (2001-10).
AB - OBJECTIVES: To assess trends in benzodiazepine use from 2001 to 2010 in older
adults in U.S. ambulatory clinics and emergency departments (EDs). DESIGN:
Retrospective analysis. SETTING: 2001 to 2010 National Ambulatory Medical Care
Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS).
PARTICIPANTS: Individuals aged 65 and older for whom the reason for visit might
prompt a physician to use a benzodiazepine (e.g., anxiety, detoxification, back
sprain). MEASUREMENTS: The NAMCS and NHAMCS were used to evaluate U.S. ambulatory
clinic and ED visits. Encounters involving individuals aged 65 and older for whom
a benzodiazepine might be prescribed were analyzed. Trends in benzodiazepine use
in these visits were explored, and predictors of use were assessed using survey
weighted chi-square tests and logistic regression. RESULTS: From 2001 to 2010,
benzodiazepines were used in 16.6 million of 133.3 million ambulatory clinic
visits and 1.9 million of 18.1 million ED visits with the selected reasons for
the visits. There was no change in benzodiazepine use in either setting over the
study period, although benzodiazepine use for those aged 85 and older increased
from 8.9% to 19.3% in ambulatory clinics and 10.1% to 17.2% in EDs. Individuals
visiting clinics with anxiety were five times as likely to receive
benzodiazepines (odds ratio (OR) = 4.8), and those in EDs were twice as likely
(OR = 2.3). CONCLUSION: Despite safety concerns, benzodiazepine use in older
adults in U.S. ambulatory clinics and EDs did not change from 2001 to 2010. In
the oldest individuals, who are at higher risk of adverse events, a greater
increase was seen than in those aged 65 to 84. Additional measures may be needed
to promote alternatives to benzodiazepines.
PMID- 26415837
TI - Alzheimer's disease drug development based on Computer-Aided Drug Design.
AB - Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by
the excessive deposition of amyloids in the brain. The pathological features
mainly include the extracellular amyloid plaques and intracellular
neurofibrillary tangles, which are the production of amyloid precursor protein
(APP) processed by the alpha-, beta- and gamma-secretases. Based on the amyloid
cascade hypotheses of AD, a large number of amyloid-beta agents and secretase
inhibitors against AD have been recently developed by using computational
methods. This review article describes pathophysiology of AD and the structure of
the Abeta plaques, beta- and gamma-secretases, and discusses the recent advances
in the development of the amyloid agents for AD therapy and diagnosis by using
Computer-Aided Drug Design approach.
PMID- 26415838
TI - Ultrahigh volumetric capacitance and cyclic stability of fluorine and nitrogen co
doped carbon microspheres.
AB - Highly porous nanostructures with large surface areas are typically employed for
electrical double-layer capacitors to improve gravimetric energy storage
capacity; however, high surface area carbon-based electrodes result in poor
volumetric capacitance because of the low packing density of porous materials.
Here, we demonstrate ultrahigh volumetric capacitance of 521 F cm(-3) in aqueous
electrolytes for non-porous carbon microsphere electrodes co-doped with fluorine
and nitrogen synthesized by low-temperature solvothermal route, rivaling
expensive RuO2 or MnO2 pseudo-capacitors. The new electrodes also exhibit
excellent cyclic stability without capacitance loss after 10,000 cycles in both
acidic and basic electrolytes at a high charge current of 5 A g(-1). This work
provides a new approach for designing high-performance electrodes with
exceptional volumetric capacitance with high mass loadings and charge rates for
long-lived electrochemical energy storage systems.
PMID- 26415839
TI - PUPIL: A Software Integration System for Multi-Scale QM/MM-MD Simulations and Its
Application to Biomolecular Systems.
AB - PUPIL (Program for User Package Interfacing and Linking) implements a distinctive
multi-scale approach to hybrid quantum mechanical/molecular mechanical molecular
dynamics (QM/MM-MD) simulations. Originally developed to interface different
external programs for multi-scale simulation with applications in the materials
sciences, PUPIL is finding increasing use in the study of complex biological
systems. Advanced MD techniques from the external packages can be applied readily
to a hybrid QM/MM treatment in which the forces and energy for the QM region can
be computed by any of the QM methods available in any of the other external
packages. Here, we give a survey of PUPIL design philosophy, main features, and
key implementation decisions, with an orientation to biomolecular simulation. We
discuss recently implemented features which enable highly realistic simulations
of complex biological systems which have more than one active site that must be
treated concurrently. Examples are given.
PMID- 26415841
TI - A Practical Quantum Mechanics Molecular Mechanics Method for the Dynamical Study
of Reactions in Biomolecules.
AB - Quantum mechanics/molecular mechanics (QM/MM) methods are excellent tools for the
modeling of biomolecular reactions. Recently, we have implemented a new QM/MM
method (Fireball/Amber), which combines an efficient density functional theory
method (Fireball) and a well-recognized molecular dynamics package (Amber),
offering an excellent balance between accuracy and sampling capabilities. Here,
we present a detailed explanation of the Fireball method and Fireball/Amber
implementation. We also discuss how this tool can be used to analyze reactions in
biomolecules using steered molecular dynamics simulations. The potential of this
approach is shown by the analysis of a reaction catalyzed by the enzyme triose
phosphate isomerase (TIM). The conformational space and energetic landscape for
this reaction are analyzed without a priori assumptions about the protonation
states of the different residues during the reaction. The results offer a
detailed description of the reaction and reveal some new features of the
catalytic mechanism. In particular, we find a new reaction mechanism that is
characterized by the intramolecular proton transfer from O1 to O2 and the
simultaneous proton transfer from Glu 165 to C2.
PMID- 26415840
TI - Efficient Calculation of Enzyme Reaction Free Energy Profiles Using a Hybrid
Differential Relaxation Algorithm: Application to Mycobacterial Zinc Hydrolases.
AB - Determination of the free energy profile for an enzyme reaction mechanism is of
primordial relevance, paving the way for our understanding of the enzyme's
catalytic power at the molecular level. Although hybrid, mostly DFT-based, QM/MM
methods have been extensively applied to this type of studies, achieving accurate
and statistically converged results at a moderate computational cost is still an
open challenge. Recently, we have shown that accurate results can be achieved in
less computational time, combining Jarzynski's relationship with a hybrid
differential relaxation algorithm (HyDRA), which allows partial relaxation of the
solvent during the nonequilibrium steering of the reaction. In this work, we have
applied this strategy to study two mycobacterial zinc hydrolases. Mycobacterium
tuberculosis infections are still a worldwide problem and thus characterization
and validation of new drug targets is an intense field of research. Among
possible drug targets, recently two essential zinc hydrolases, MshB (Rv1170) and
MA-amidase (Rv3717), have been proposed and structurally characterized. Although
possible mechanisms have been proposed by analogy to the widely studied human Zn
hydrolases, several key issues, particularly those related to Zn coordination
sphere and its role in catalysis, remained unanswered. Our results show that
mycobacterial Zn hydrolases share a basic two-step mechanism. First, the
attacking water becomes deprotonated by the conserved base and establishes the
new C-O bond leading to a tetrahedral intermediate. The intermediate requires
moderate reorganization to allow for proton transfer to the amide N and C-N bond
breaking to occur in the second step. Zn ion plays a key role in stabilizing the
tetrahedral intermediate and balancing the negative charge of the substrate
during hydroxide ion attack. Finally, comparative analysis of other Zn hydrolases
points to a convergent mechanistic evolution.
PMID- 26415842
TI - Explicit Drug Re-positioning: Predicting Novel Drug-Target Interactions of the
Shelved Molecules with QM/MM Based Approaches.
AB - With the demand to enhance the speed of the drug discovery process there has been
an increased usage of computational approaches in drug discovery studies. However
because of their probabilistic outcomes, the challenge is to exactly mimic the
natural environment which can provide the exact charge polarization effect while
estimating the binding energy between protein and ligand. There has been a large
number of scoring functions from simple one to the complex one available for
estimating binding energy. The quantum mechanics/molecular mechanics (QM/MM)
hybrid approach has been the preferred choice of interest since last decade for
modeling reactions in biomolecular systems. The application of QM/MM approach has
been expanded right from rescoring the already known complexes and depicting the
correct position of some novel molecule to ranking a large number of molecules.
It is expected that the application of QM/MM-based scoring will grow in all areas
of drug discovery. However, the most promising area will be its application in
repositioning, that is, assigning novel functions or targets to the already
existing drugs, as this would stop the rising attrition rates as well as reduce
the overall time and cost of drug discovery procedure.
PMID- 26415843
TI - Enzymatic Halogenases and Haloperoxidases: Computational Studies on Mechanism and
Function.
AB - Despite the fact that halogenated compounds are rare in biology, a number of
organisms have developed processes to utilize halogens and in recent years, a
string of enzymes have been identified that selectively insert halogen atoms
into, for instance, a CH aliphatic bond. Thus, a number of natural products,
including antibiotics, contain halogenated functional groups. This unusual
process has great relevance to the chemical industry for stereoselective and
regiospecific synthesis of haloalkanes. Currently, however, industry utilizes few
applications of biological haloperoxidases and halogenases, but efforts are being
worked on to understand their catalytic mechanism, so that their catalytic
function can be upscaled. In this review, we summarize experimental and
computational studies on the catalytic mechanism of a range of haloperoxidases
and halogenases with structurally very different catalytic features and
cofactors. This chapter gives an overview of heme-dependent haloperoxidases,
nonheme vanadium-dependent haloperoxidases, and flavin adenine dinucleotide
dependent haloperoxidases. In addition, we discuss the S-adenosyl-l-methionine
fluoridase and nonheme iron/alpha-ketoglutarate-dependent halogenases. In
particular, computational efforts have been applied extensively for several of
these haloperoxidases and halogenases and have given insight into the essential
structural features that enable these enzymes to perform the unusual halogen atom
transfer to substrates.
PMID- 26415844
TI - The Importance of the MM Environment and the Selection of the QM Method in QM/MM
Calculations: Applications to Enzymatic Reactions.
AB - In this chapter, we discuss the influence of an anisotropic protein environment
on the reaction mechanisms of saccharopine reductase and uroporphyrinogen
decarboxylase, respectively, via the use of a quantum mechanical and molecular
mechanical (QM/MM) approach. In addition, we discuss the importance of selecting
a suitable DFT functional to be used in a QM/MM study of a key intermediate in
the mechanism of 8R-lipoxygenase, a nonheme iron enzyme. In the case of
saccharopine reductase, while the enzyme utilizes a substrate-assisted catalytic
pathway, it was found that only through treating the polarizing effect of the
active site, via the use of an electronic embedding formalism, was agreement with
experimental kinetic data obtained. Similarly, in the case of uroporphyrinogen
decarboxylase, the effect of the protein environment on the catalytic mechanism
was found to be such that the calculated rate-limiting barrier is in good
agreement with related experimentally determined values for the first
decarboxylation of the substrate. For 8R-lipoxygenase, it was found that the
geometries and energies of the multicentered open-shell intermediate complexes
formed during the mechanism are quite sensitive to the choice of the density
functional theory method. Thus, while density functional theory has become the
method of choice in QM/MM studies, care must be taken in the selection of a
particular high-level method.
PMID- 26415845
TI - QM and QM/MM Methods Compared: Case Studies on Reaction Mechanisms of
Metalloenzymes.
AB - The review focus is a comparison of QM and QM/MM modeling techniques applied to
study of metalloenzymes. The chapter aim is to highlight many of the advantages
and potential pitfalls of the exciting and revolutionary QM/MM techniques using
both large QM/MM systems and QM-only modeling as references. The review is
illustrated by case studies for isopenicillin N synthase, ethylbenzene
dehydrogenase, cytochrome P450 enzyme, AlkB DNA repair enzyme as well as 4
hydroxyphenylpyruvate dioxygenase. We find many advantages in various QM/MM
techniques, over the more traditional QM cluster approaches, while at the same
time offering some advice about how to avoid potential complications arising from
some of these approaches' most notable drawbacks. We conclude that while there
will always be an important role for QM cluster models, in computational studies,
the revolutionary developments in QM/MM techniques open a bright and exciting
future of new research.
PMID- 26415846
TI - QM/MM Studies Reveal How Substrate-Substrate and Enzyme-Substrate Interactions
Modulate Retaining Glycosyltransferases Catalysis and Mechanism.
AB - Glycosyltransferases (GTs) catalyze the biosynthesis of glycosidic linkages by
transferring a monosaccharide from a nucleotide sugar donor to an acceptor
substrate, and they do that with exquisite regio- and stereospecificity.
Retaining GTs act with retention of the configuration at the anomeric carbon of
the transferred sugar. Their chemical mechanism has been under debate for long as
conclusive experimental data to confirm the mechanism have been elusive. In the
past years, quantum mechanical/molecular mechanical (QM/MM) calculations have
shed light on the mechanistic discussion. Here, we review the work carried out in
our group investigating three of these retaining enzymes (LgtC, alpha3GalT, and
GalNAc-T2). Our results support the controversial front-side attack mechanism as
the general mechanism for most retaining GTs. The latest structural data are in
agreement with these findings. QM/MM calculations have revealed how enzyme
substrate and substrate-substrate interactions modulate the transfer reaction
catalyzed by these enzymes. Moreover, they provide an explanation on why in some
cases a strong nucleophilic residue is found on the beta-face of the sugar,
opening the door to a shift toward a double-displacement mechanism.
PMID- 26415847
TI - Excited States and Photochemistry of Chromophores in the Photoactive Proteins
Explored by the Combined Quantum Mechanical and Molecular Mechanical
Calculations.
AB - A photoactive protein usually contains a unique chromophore that is responsible
for the initial photoresponse and functions of the photoactive protein are
determined by the interaction between the chromophore and its protein
surroundings. The combined quantum mechanical and molecular mechanical (QM/MM)
approach is demonstrated to be a very useful tool for exploring structures and
functions of a photoactive protein with the chromophore and its protein
surroundings treated by the QM and MM methods, respectively. In this review, we
summarize the basic formulas of the QM/MM approach and emphasize its applications
to excited states and photoreactions of chromophores in rhodopsin protein,
photoactive yellow protein, and green fluorescent protein.
PMID- 26415848
TI - Preface.
PMID- 26415849
TI - NetBenchmark: a bioconductor package for reproducible benchmarks of gene
regulatory network inference.
AB - BACKGROUND: In the last decade, a great number of methods for reconstructing gene
regulatory networks from expression data have been proposed. However, very few
tools and datasets allow to evaluate accurately and reproducibly those methods.
Hence, we propose here a new tool, able to perform a systematic, yet fully
reproducible, evaluation of transcriptional network inference methods. RESULTS:
Our open-source and freely available Bioconductor package aggregates a large set
of tools to assess the robustness of network inference algorithms against
different simulators, topologies, sample sizes and noise intensities.
CONCLUSIONS: The benchmarking framework that uses various datasets highlights the
specialization of some methods toward network types and data. As a result, it is
possible to identify the techniques that have broad overall performances.
PMID- 26415850
TI - No hospital left behind? Education policy lessons for value-based payment in
healthcare.
AB - Value-based payment systems have been widely implemented in healthcare in an
effort to improve the quality of care. However, these programs have not broadly
improved quality, and some evidence suggests that they may increase inequities in
care. No Child Left Behind is a parallel effort in education to address uneven
achievement and inequalities. Yet, by penalizing the lowest performers, No Child
Left Behind's approach to accountability has led to a number of unintended
consequences. This article draws lessons from education policy, arguing that
financial incentives should be designed to support the lowest performers to
improve quality.
PMID- 26415851
TI - A forgotten chiral spiro compound revisited: 3,3'-dimethyl-3H,3'H-2,2'
spirobi[[1,3]benzothiazole].
AB - The title compound was obtained as a side product during dimerization-oxidation
steps of the carbene generated from N-methylbenzothiazolium iodide.
Chromatography on (S,S)-Whelk O1 column showed on cooling a typical plateau shape
chromatogram indicating an exchange between two enantiomers on the column. The
thermal barrier to racemization was determined (85 kJ.mol(-1) at 10 degrees C)
by dynamic high-performance liquid chromatography (DHPLC).The absolute
configuration of the first (M) and second eluted (P) enantiomers on the (S, S)
Whelk O1 column was established by comparing the reconstructed circular dichroism
(CD) spectra from the CD detector signal and the calculated CD spectrum of the
(P) enantiomer. Mass spectrometry revealed that 3,3'-dimethyl-3H,3'H-2,2'
spirobi[[1,3]benzothiazole] can be viewed as a masked thiophenate attached to a
benzothiazolium framework.
PMID- 26415852
TI - Synthesis, molecular structure, and chiroptical properties of dibenzylidene
derivatives of bicyclo[3.3.1]nonane and brexane.
AB - Synthesis of several enantiomerically pure unsaturated bicyclo[3.3.1]nonane and
related brexane (tricyclo[4.3.0.0(3,7) ]nonane) derivatives bearing exocyclic
benzylidene substituents from readily available (+)-(1S,5S)-bicyclo[3.3.1]nonane
2,6-dione was accomplished. Molecular geometry and chiroptical properties of
compounds with enone and styrene chromophores were studied by X-ray diffraction
analysis, molecular modeling, and circular dichroism (CD) spectroscopy.
Difunctional 3,7-dibenzylidenebicyclo[3.3.1]nonanes, such as and , exhibited
intense CD couplets, arising from the exciton coupling between the two
unsaturated chromophores. The observed negative sign of the exciton couplets is
congruent with the negative twist (negative chirality) defined by the two
interacting transition dipoles. The sign of the Cotton effect corresponding to
the pi->pi* transitions in the CD spectra of monoenone and tricyclic brexane
acetate was correlated with the intrinsic dissymmetry (helicity) of the styrene
chromophore.
PMID- 26415853
TI - Zwitterionic phosphorylated quinines as chiral solvating agents for NMR
spectroscopy.
AB - Because of their unique 3D arrangement, naturally occurring Cinchona alkaloids
and their synthetic derivatives have found wide-ranging applications in chiral
recognition. Recently, we determined the enantioselective properties of C-9
phosphate mixed triesters of quinine as versatile chiral solvating agents in
nuclear magnetic resonance (NMR) spectroscopy. In the current study, we introduce
new zwitterionic members of this class of molecules containing a negatively
charged phosphate moiety (i.e., ethyl, n-butyl and phenyl hydrogen quininyl
phosphate). An efficient approach for synthesizing these compounds is elaborated,
and full characterization, including conformational and autoaggregation phenomena
studies, was performed. Therefore, their ability to induce NMR anisochrony of
selected enantiomeric substrates (i.e., primarily N-DNB-protected amino acids and
their methyl esters) was analyzed compared to uncharged diphenyl quininyl
phosphate and its positively charged quaternary ammonium hydrochloride salt. In
addition, (1) H and (13) C NMR experiments revealed their enantiodiscrimination
potential toward novel analytes, such as secondary amines and nonprotected amino
acids.
PMID- 26415856
TI - Functional Micro-Dispensers based on Micro-Electro-Mechanical-Systems (MEMS)
integrated with fabrics as functional materials to protect humans from mosquito
feeding.
AB - Functional Micro-Dispensers (FMDs) based on Micro-Electro-Mechanical-Systems
(MEMS) were designed to deliver spatial repellents that reduce the ability of
mosquitoes to feed on humans. FMDs were integrated with fabrics as functional
materials for protection against mosquito bites. The use of MEMS devices provides
an unprecedented control over the release kinetics by means of integration with
electronics for selective and timely activation of each device to perform
controlled release of pesticides in air. In addition, because MEMS manufacturing
techniques evolved from the microelectronic industry, FMDs can be mass produced
at very low cost. Trials using FMDs that contained transfluthrin improved
protection against mosquito feeding in human subjects above that of permethrin
treated uniform fabric worn on the arm of the volunteer. The overall reduction in
feeding was approximately 90% compared to the untreated fabric control, and about
50% reduction compared to the permethrin-treated fabric control. The devices were
efficacious over course of 32 days. FMDs have the potential for a simple and cost
effective implementation for mass adoption as wearable devices integrated in
fabrics as active functional materials.
PMID- 26415855
TI - Chemically modified RNA activated matrices enhance bone regeneration.
AB - There exists a dire need for improved therapeutics to achieve predictable bone
regeneration. Gene therapy using non-viral vectors that are safe and efficient at
transfecting target cells is a promising approach to overcoming the drawbacks of
protein delivery of growth factors. Here, we investigated the transfection
efficiency, cytotoxicity, osteogenic potential and in vivo bone regenerative
capacity of chemically modified ribonucleic acid (cmRNA) (encoding BMP-2)
complexed with polyethylenimine (PEI) and made comparisons with PEI complexed
with conventional plasmid DNA (encoding BMP-2). The polyplexes were fabricated at
an amine (N) to phosphate (P) ratio of 10 and characterized for transfection
efficiency using human bone marrow stromal cells (BMSCs). The osteogenic
potential of BMSCs treated with these polyplexes was validated by determining the
expression of bone-specific genes, osteocalcin and alkaline phosphatase as well
as through the detection of bone matrix deposition. Using a calvarial bone defect
model in rats, it was shown that PEI-cmRNA (encoding BMP-2)-activated matrices
promoted significantly enhanced bone regeneration compared to PEI-plasmid DNA
(BMP-2)-activated matrices. Our proof of concept study suggests that scaffolds
loaded with non-viral vectors harboring cmRNA encoding osteogenic proteins may be
a powerful tool for stimulating bone regeneration with significant potential for
clinical translation.
PMID- 26415857
TI - Down-regulated microRNA-124 expression as predictive biomarker and its prognostic
significance with clinicopathological features in breast cancer patients.
AB - BACKGROUND: MicroRNAs (miRNAs) have been documented as playing important roles in
cancer development. In this study, we investigated to clarify the
clinicopathological significance and prognostic value of miR-124 in breast
cancer. METHODS: Quantitative Real-time PCR method was used to assess the
expression levels of miR-124 in breast cancer patients and the association of miR
124 expression levels with the clinicopathological characteristics in breast
cancer patients. Survival and Multivariate Cox proportional hazards model
analysis was used to evaluate whether the miR-124 expression level and various
clinicopathological characteristics were independent prognostic marker for breast
cancer patients. RESULTS: We found that the lower expression of miR-124 in breast
cancer specimens compared with corresponding adjacent normal breast tissues P <
0.05. Results showed that decreased expression of miR-124 was significantly
related to advanced clinical stage (stage III and IV) (P = 0.021) and positive
lymph node-metastasis (P = 0.011). Patients with low expression of miR-124 had
significantly shorter overall survival (70.2 %) than patients who had cancers
with high miR-124 expression (29.8), (logrank test P = 0.021). Moreover,
Multivariate Cox proportional hazards model analysis indicated that lowr miR-124
expression was found to be independently linked to poor survival of patients with
breast cancer and other factors were not significantly associated with survival
of patients. CONCLUSION: Our data suggested that decreased expression of miR-124
has prognostic value in breast cancer and may serve as a prognostic marker for
breast cancer, and also downregulation of miR-124 was inversely associated with
the lymph node metastasis in breast cancer.
PMID- 26415854
TI - Surface plasmon resonance as a high throughput method to evaluate specific and
non-specific binding of nanotherapeutics.
AB - Surface plasmon resonance (SPR) is a powerful analytical technique used to
quantitatively examine the interactions between various biomolecules, such as
proteins and nucleic acids. The technique has been particularly useful in
screening and evaluating binding affinity of novel small molecule and biomolecule
derived therapeutics for various diseases and applications including lupus
medications, thrombin inhibitors, HIV protease inhibitors, DNA gyrase inhibitors
and many others. Recently, there has been increasing interest in nanotherapeutics
(nanoRx), due to their unique properties and potential for controlled release of
encapsulated drugs and structure-specific targeting to diseased tissues. NanoRx
offer the potential to solve many drug delivery challenges by enabling, specific
interactions between molecules on the surface of the nanoparticle and molecules
in the diseased tissue, while minimizing off-target interactions toward non
diseased tissues. These properties are largely dependent upon careful control and
balance of nanoRx interactions and binding properties with tissues in vivo. Given
the great promise of nanoRx with regard to engineering specific molecular
interactions, SPR can rapidly quantify small aliquots of nanoRx formulations for
desired and undesired molecular interactions. Moving forward, we believe that
utilization of SPR in the screening and design of nanoRx has the potential to
greatly improve the development of targeted nanoRx formulations and eventually
lead to improved therapeutic efficacy. In this review, we discuss (1) the
fundamental principles of SPR and basic quantitative analysis of SPR data, (2)
previous applications of SPR in the study of non-particulate therapeutics and
nanoRx, and (3) future opportunities for the use of SPR in the evaluation of
nanoRx.
PMID- 26415858
TI - Bladder symptoms and urodynamic observations of patients with endometriosis
confirmed by laparoscopy.
AB - INTRODUCTION AND HYPOTHESIS: Patients with deep infiltrating pelvic endometriosis
(DIE) often describe having lower urinary tract symptoms (LUTS). Bladder pain
syndrome in women is also often associated with endometriosis. In this study, we
aimed to describe the characteristics of LUTS and urodynamic observations in
patients with posterior endometriosis versus those with posterior and anterior
endometriosis. METHODS: This was a prospective observational study of 30 patients
from two gynecologic surgical settings with experience in DIE surgery. All
patients underwent preoperative standardized investigation including detailed
evaluation of LUTS and urodynamic studies. During surgery, endometriosis
locations were recorded and correlated to symptoms and urodynamic observations.
RESULTS: Twenty-three patients (76.7 %) had one or more LUTS symptoms and 29
(96.7 %) had one or more abnormalities at urodynamic examination. At surgery, all
patients had posterior endometriosis and ten of them also had anterior
endometriosis. Patients with anterior endometriosis had increased bladder
sensation (90.0 % versus 45.0 %, p = 0.024) and painful bladder filling (70.0 %
versus 30.0, p = 0.04) compared with patients with posterior endometriosis only.
Voiding symptoms (60.0 %), impairment of flowmetry (30.0 %), and increased
maximum urethral closure pressure (90.0 %) were frequent and not correlated with
any specific location. CONCLUSIONS: Endometriosis infiltrating the bladder wall
is associated with painful bladder symptoms. Dysfunctional voiding suggests an
impairment of the inferior hypogastric plexus by posterior DIE. Clinical
preoperative evaluation of bladder function should be systematic; urodynamic
tests could be of interest in selected patients with DIE. Endometriosis may be a
major cause of bladder pain syndrome.
PMID- 26415859
TI - Reduced apurinic/apyrimidinic endonuclease 1 activity and increased DNA damage in
mitochondria are related to enhanced apoptosis and inflammation in the brain of
senescence- accelerated P8 mice (SAMP8).
AB - The senescence- accelerated mouse prone 8 (SAMP8) is a well- characterized animal
model of senescence that shows early age- related neurodegeneration with
impairment in learning and memory skills when compared with control senescence-
resistant mice (SAMR1). In the current study, we investigated whether such
impairment could be partly due to changes in mitochondrial DNA (mtDNA) repair
capacity and mitochondrial DNA damage in the brain of SAMP8 mice. Besides we
studied whether these potential changes were related to modifications in two
major processes likely involved in aging and neurodegeneration: apoptosis and
inflammation. We observed that the specific activity of one of the main mtDNA
repair enzymes, the mitochondrial APE1, showed an age- related reduction in SAMP8
animals, while in SAMR1 mice mitochondrial APE1 increased with age. The reduction
in mtAPE1 activity in SAMP8 animals was associated with increased levels of the
DNA oxidative damage marker 8oxodG in mtDNA. Our results also indicate that these
changes were related to a premature increase in apoptotic events and inflammation
in the brain of SAMP8 mice when compared to SAMR1 counterparts. We suggest that
the premature neurodegenerative phenotype observed in SAMP8 animals might be due,
at least in part, to changes in the processing of mtDNA oxidative damage, which
would lead to enhancement of apoptotic and inflammatory processes.
PMID- 26415860
TI - Hemoglobin thresholds for transfusion in pediatric patients at a large academic
health center.
AB - BACKGROUND: Although prior studies support the use of a hemoglobin (Hb)
transfusion trigger of 7 to 8 g/dL for most hospitalized adults, there are few
studies in pediatric populations. We therefore investigated transfusion practices
and Hb triggers in hospitalized children. STUDY DESIGN AND METHODS: We performed
a historical cohort study comparing transfusion practices in hospitalized
children by service within a single academic institution. Blood utilization data
from transfused patients (n = 3370) were obtained from electronic records over 4
years. Hb triggers and posttransfusion Hb levels were defined as the lowest and
last Hb measured during hospital stay, respectively, in transfused patients. The
mean and percentile distribution for Hb triggers were compared to the evidence
based restrictive transfusion threshold of 7 g/dL. RESULTS: Mean Hb triggers were
above the restrictive trigger (7 g/dL) for eight of 12 pediatric services. Among
all of the services, there were significant differences between the mean Hb
triggers (>2.5 g/dL, p<0.0001) and between the posttransfusion Hb levels (>3
g/dL, p < 0.0001). The variation between the 10th and 90th percentiles for
triggers (up to 4 g/dL, p < 0.0001) and posttransfusion Hb levels (up to 6 g/dL,
p < 0.0001) were significant. Depending on the service, between 25 and 90% of
transfused patients had Hb triggers higher than the restrictive range.
CONCLUSIONS: Red blood cell (RBC) transfusion therapy varies significantly in
hospitalized children with mean Hb triggers above a restrictive threshold for
most services. Our findings suggest that transfusions may be overused and that
implementing a restrictive transfusion strategy could decrease the use of RBC
transfusions, thereby reducing the associated risks and costs.
PMID- 26415861
TI - Spontaneous social distancing in response to a simulated epidemic: a virtual
experiment.
AB - BACKGROUND: Studies of social distancing during epidemics have found that the
strength of the response can have a decisive impact on the outcome. In previous
work we developed a model of social distancing driven by individuals' risk
attitude, a parameter which determines the extent to which social contacts are
reduced in response to a given infection level. We showed by simulation that a
strong response, driven by a highly cautious risk attitude, can quickly suppress
an epidemic. However, a moderately cautious risk attitude gives weak control and,
by prolonging the epidemic without reducing its impact, may yield a worse outcome
than doing nothing. In real societies, social distancing may arise spontaneously
from individual choices rather than being imposed centrally. There is little data
available about this as opportunistic data collection during epidemics is
difficult. Our study uses a simulated epidemic in a computer game setting to
measure the social distancing response. METHODS: Two hundred thirty participants
played a computer game simulating an epidemic on a spatial network. The player
controls one individual in a population of 2500 (with others controlled by
computer) and decides how many others to contact each day. To mimic real-world
trade-offs, the player is motivated to make contact by being rewarded with
points, while simultaneously being deterred by the threat of infection.
Participants completed a questionnaire regarding psychological measures of health
protection motivation. Finally, simulations were used to compare the
experimentally-observed response to epidemics with no response. RESULTS:
Participants reduced contacts in response to infection in a manner consistent
with our model of social distancing. The experimentally observed response was too
weak to halt epidemics quickly, resulting in a somewhat reduced attack rate and a
substantially reduced peak attack rate, but longer duration and fewer social
contacts, compared to no response. Little correlation was observed between
participants' risk attitudes and the psychological measures. CONCLUSIONS: Our
cognitive model of social distancing matches responses to a simulated epidemic.
If these responses indicate real world behaviour, spontaneous social distancing
can be expected to reduce peak attack rates. However, additional measures are
needed if it is important to stop an epidemic quickly.
PMID- 26415862
TI - Genetic Diversity of Brazilian Bovine Pestiviruses Detected Between 1995 and
2014.
AB - Pestivirus infections in ruminants result in significant economic losses
worldwide. The aetiological agents are three species from the genus Pestivirus,
family Flaviviridae, including bovine viral diarrhoea virus type 1 (BVDV-1), BVDV
2, border disease virus (BDV), and an atypical pestivirus named HoBi-like
pestivirus. In this study, eighty-nine pestivirus isolates that were collected in
Brazil between 1995 and 2014 and that originated from either cattle, fetal bovine
serum (FBS) or as cell culture contaminants were genotyped based on a comparison
of gene sequences from their 5' untranslated regions (5'UTR), N-terminal
autoprotease (Npro ) and envelope glycoprotein 2 (E2). Of these isolates, 53.9%
of the sequences were genotyped as BVDV-1, 33.7% as BVDV-2 and 12.4% as HoBi-like
pestivirus. The prevalence of subgenotypes within the species was as follows:
BVDV-1a (35.9%), BVDV-2b (31.4%), BVDV-1b (10.1%), BVDV-1d (6.7%), BVDV-2c (2.2%)
and BVDV-1e (1.1%). BVDV-2c and BVDV-1e were detected for the first time in
Brazil. This study revealed extensive genetic diversity among Brazilian
pestivirus isolates, and the combination of pestiviruses that was detected is
unique to Brazil. This information may serve as a foundation for designing and
evaluating diagnostic tools and in the development of more effective vaccines;
therefore, it may potentially contribute to pestivirus control and eradication.
PMID- 26415863
TI - Squamous cell carcinoma arising from a Zenker's diverticulum: contribution of FDG
PET/CT to the diagnosis.
PMID- 26415864
TI - Cloning and molecular ontogeny of digestive enzymes in fed and food-deprived
developing gilthead seabream (Sparus aurata) larvae.
AB - We have determined the expression pattern of key pancreatic enzymes precursors
(trypsinogen, try; chymotrypsinogen, ctrb; phospholipase A2, pla2; bile salt
activated lipase, cel; and alpha-amylase, amy2a) during the larval stage of
gilthead seabream (Sparus aurata) up to 60days after hatching (dph). Previously,
complete sequences of try, cel, and amy2a were cloned and phylogenetically
analyzed. One new isoform was found for cel transcript (cel1b). Expression of all
enzyme precursors was detected before the mouth opening. Expression of try and
ctrb increased during the first days of development and then maintained high
values with some fluctuations during the whole larval stage. The prolipases pla2
and cel1b increased from first-feeding with irregular fluctuation until the end
of the experiment. Contrarily, cel1a maintained low expression values during most
of the larval stage increasing at the end of the period. Nevertheless, cel1a
expression was negligible as compared with cel1b. The expression of amy2a sharply
increased during the first week followed by a gradual decrease. In addition, a
food-deprivation experiment was performed to find the differences in relation to
presence/absence of gut content after the opening of the mouth. The food-deprived
larvae died at 10dph. The expression levels of all digestive enzymes increased up
to 7dph, declining sharply afterwards. This expression pattern up to 7dph was the
same observed in fed larvae, confirming the genetic programming during the early
development. Main digestive enzymes in gilthead seabream larvae exhibited the
same expression profiles than other marine fish with carnivorous preferences in
their juvenile stages.
PMID- 26415865
TI - Structural and functional characterization of neuromedin S in the teleost fish,
zebrafish (Danio rerio).
AB - Neuromedin S (NMS) has been demonstrated to have important roles in many
vertebrate physiological processes. However, the function of NMS in teleost
fishes remains unclear. We explored the physiological roles of the NMS gene in
the zebrafish model. An NMS cDNA was cloned from zebrafish brain tissue, and the
full-length cDNA sequence was 521 bp in length and encoded a precursor of 110
amino acid residues. Interestingly, fish prepro-NMS is predicted to generate a
short 34-residue peptide, designated as NMS-related peptide (NMSRP). Zebrafish
prepro-NMS does not contain the NMS peptide which is found in the NMS precursors
of mammals, and just retains the MNSRP peptide. A multiple-species sequence
alignment showed that NMSRPs are conserved among the other sampled vertebrates.
Zebrafish NMS mRNA was detected by RT-PCR revealing a tissue-specific
distribution with high levels of expression in the brain, spleen, ovary,
pituitary, and muscle. Furthermore, the locations of NMS-expressing cells in the
zebrafish brain were detected by in situ hybridization in the parvocellular
preoptic nucleus (PPa), the ventral zone of the periventricular hypothalamus
(Hv), and lateral hypothalamic nucleus (LH). The levels of NMS mRNA in the
hypothalamus were significantly increased after three days of food deprivation.
Administration of zebrafish NMSRP by intraperitoneal injection significantly
promoted the expression of neuropeptide Y (NPY) and orexin, suggesting an
orexigenic role for NMSRP in zebrafish. The present study offers a new
understanding of the NMS gene in vertebrates and increases our knowledge of the
neuroendocrine regulation of feeding.
PMID- 26415866
TI - Microfluidics-based single-step preparation of injection-ready polymeric
nanosystems for medical imaging and drug delivery.
AB - Translation of therapeutic polymeric nanosystems to patients and industry
requires simplified, reproducible and scalable methods for assembly and loading.
A single-step in-line process based on nanocoprecipitation of oxazoline-siloxane
block copolymers in flow-focusing poly(dimethylsiloxane) microfluidics was
designed to manufacture injection-ready nanosystems. Nanosystem characteristics
could be controlled by copolymer concentration, block length and chemistry,
microchannel geometry, flow rate, aqueous/organic flow rate ratio and payload
concentration. The well-tolerated nanosystems exhibited differential cell binding
and payload delivery and could confer sensitivity to photodynamic therapy to HeLa
cancer cells. Such injection-ready nanosystems carrying drugs, diagnostic or
functional materials may facilitate translation to clinical application.
PMID- 26415867
TI - Erratum to: Optimal timing of clopidogrel discontinuation in Japanese patients:
platelet aggregation test using the VerifyNow(r) system.
PMID- 26415868
TI - Necrotizing Fasciitis and The Diabetic Foot.
AB - Necrotizing fasciitis (NF) represents a rapidly progressive, life-threatening
infection involving skin, soft tissue, and deep fascia. An early diagnosis is
crucial to treat NF effectively. The disease is generally due to an external
trauma that occurs in predisposed patients: the most important risk factor is
represented by diabetes mellitus. NF is classified into 3 different subtypes
according to bacterial strains responsible: type 1 associated to polymicrobial
infection, type 2 NF, generally associated to Streptococcus species, often
associated to Staphylococcus aureus and, eventually, Type 3, due to Gram-negative
strains, such as Clostridium difficile or Vibrio. NF is usually characterized by
the presence of the classic triad of symptoms: local pain, swelling, and
erythema. In daily clinical practice immune-compromised or neuropathic diabetic
patients present with atypical symptomatology. This explains the high percentage
of misdiagnosed cases in the emergency department and, consequently, the worse
outcome presented by these patients. Prompt aggressive surgical debridement and
antibiotic systemic therapy are the cornerstone of its treatment. These must be
associated with an accurate systemic management, consisting in nutritional
support, glycemic compensation, and hemodynamic stabilization. Innovative
methods, such as negative pressure therapy, once the acute conditions have
resolved, can help fasten the surgical wound closure. Prompt management can
improve prognosis of patients affected from NF reducing limb loss and saving
lives.
PMID- 26415869
TI - Mastering variation: variance components and personalised medicine.
AB - Various sources of variation in observed response in clinical trials and clinical
practice are considered, and ways in which the corresponding components of
variation might be estimated are discussed. Although the issues have been
generally well-covered in the statistical literature, they seem to be poorly
understood in the medical literature and even the statistical literature
occasionally shows some confusion. To increase understanding and communication,
some simple graphical approaches to illustrating issues are proposed. It is also
suggested that reducing variation in medical practice might make as big a
contribution to improving health outcome as personalising its delivery according
to the patient. It is concluded that the common belief that there is a strong
personal element in response to treatment is not based on sound statistical
evidence.
PMID- 26415870
TI - Hygromycin B-induced cell death is partly mediated by reactive oxygen species in
rice (Oryza sativa L.).
AB - The aminoglycoside antibiotic hygromycin B (Hyg) inhibits prokaryotic,
chloroplast and mitochondrial protein synthesis. Because of the toxic effect of
Hyg on plant cells, the HPT gene, encoding hygromycin phosphotransferase, has
become one of the most widely used selectable markers in plant transformation.
Yet the mechanism behind Hyg-induced cell lethality in plants is not clearly
understood. In this study, we aimed to decipher this mechanism. With Hyg
treatment, rice calli exhibited cell death, and rice seedlings showed severe
growth defects, leaf chlorosis and leaf shrinkage. Rice seedlings also exhibited
severe lipid peroxidation and protein carbonylation, for oxidative stress damage
at the cellular level. The production of reactive oxygen species such as O2(.-),
H2O2 and OH(.) was greatly induced in rice seedlings under Hyg stress, and pre
treatment with ascorbate increased resistance to Hyg-induced toxicity indicating
the existence of oxidative stress. Overexpression of mitochondrial Alternative
oxidase1a gene without HPT selection marker in rice enhanced tolerance to Hyg and
attenuated the degradation of protein content, whereas the rice plastidial
glutathione reductase 3 mutant showed increased sensitivity to Hyg. These results
demonstrate that Hyg-induced cell lethality in rice is not only due to the
inhibition of protein synthesis but also mediated by oxidative stress.
PMID- 26415871
TI - Analysis of full-text publication and publishing predictors of abstracts
presented at an Italian public health meeting (2005-2007).
AB - BACKGROUND: In Public Health, a thorough review of abstract quality evaluations
and the publication history of studies presented at scientific meetings has never
been conducted. To analyse the long-term outcome of quality abstracts submitted
to conferences of Italian Society of Hygiene and Public Health (SItI) from 2005
to 2007, we conducted a second analysis of previously published material aiming
to estimate full-text publication rate of high quality abstract presented at
Italian public health meetings, and to identify predictors of full-text
publication. METHODS: The search was undertaken through scientific databases and
search engines and through the web sites of the major Italian journals of Public
Health. For each publication confirmed as a full text paper, the journal name,
impact factor, year of publication, gender of the first author, type of study
design, characteristics of the results and sample size were collected. RESULTS:
The overall publication rate of the abstracts presented is 23.5%; most of the
papers were published in Public Health journals (average impact factor: 3.007).
Non universitary affiliation had resulted in a lower probability of publication,
while some of the Conference topics had predisposed the studies to an increased
likelihood of publication as well as poster form presentation. CONCLUSIONS: The
method presented in this study provides a good framework for the evaluation of
the scientific evidence. The findings achieved should be taken into consideration
by the Scientific Societies during the contributions selection phase, with the
aim of achieving a continuous improvement of work quality. In the future, it
would be interesting to survey the abstract authors to identify reasons for
unpublished data.
PMID- 26415873
TI - Health knowledge and health practices in Makeni, Sierra Leone: a community-based
household survey.
AB - BACKGROUND: We characterize health knowledge and practices in urban and rural
Makeni, Sierra Leone, drawing comparisons between areas served by community
health workers (CHWs) with those that are not. We also inquire about causes of
infant and maternal mortality and how they are understood in the local context.
Our objective was to provide a baseline understanding of health knowledge and
practices in Makeni during the implementation of a CHW program. METHODS: We
conducted 100 household interviews in Makeni City and rural villages in the
surrounding area. We compared data between urban and rural areas to identify
differences in health knowledge and practices. RESULTS: Our sample size covered
855 individuals. Insecticide treated bednet ownership was lower in urban settings
compared to rural populations (58% vs 94%; p<.001). With regards to maternal
mortality, most respondents indicated 'no clinic' (lack of clinical care or
skipped antenatal care visits) as the primary cause (n=35), followed by bleeding
(n=17), 'lack of blood' (anemia) (n=11) and 'will of God' (n=11). CONCLUSIONS:
This initial survey of health knowledge and practices in rural and urban Makeni,
Sierra Leone, highlights some simple opportunities for community health
promotion, health education programming and behavioral interventions. Findings
will inform future iterations of a CHW training module for community health
education.
PMID- 26415872
TI - Molecular epidemiology and distribution of serotypes, genotypes, and antibiotic
resistance genes of Streptococcus agalactiae clinical isolates from Guelma,
Algeria and Marseille, France.
AB - This study describes, for the first time, the genetic and phenotypic diversity
among 93 Streptococcus agalactiae (group B Streptococcus, GBS) isolates collected
from Guelma, Algeria and Marseille, France. All strains were identified by matrix
assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
MS). The molecular support of antibiotic resistance and serotyping were
investigated by polymerase chain reaction (PCR). The phylogenetic lineage of each
GBS isolate was determined by multilocus sequence typing (MLST) and grouped into
clonal complexes (CCs) using eBURST. The isolates represented 37 sequence types
(STs), 16 of which were novel, grouped into five CCs, and belonging to seven
serotypes. Serotype V was the most prevalent serotype in our collection (44.1%).
GBS isolates of each serotype were distributed among multiple CCs, including cps
III/CC19, cps V/CC1, cps Ia/CC23, cps II/CC10, and cps III/CC17. All isolates
presented susceptibility to penicillin, whereas resistance to erythromycin was
detected in 40% and tetracycline in 82.2% of isolates. Of the 37 erythromycin
resistant isolates, 75.7% showed the macrolide-lincosamide-streptogramin B (MLSB)
resistant phenotype and 24.3% exhibited the macrolide (M)-resistant phenotype.
Constitutive MLSB resistance (46%) mediated by the ermB gene was significantly
associated with the Guelma isolates, whereas the M resistance phenotype (24.3%)
mediated by the mefA/E gene dominated among the Marseille isolates and belonged
to ST-23. Tetracycline resistance was predominantly due to tetM, which was
detected alone (95.1%) or associated with tetO (3.7%). These results provide
epidemiological data in these regions that establish a basis for monitoring
increased resistance to erythromycin and also provide insight into correlations
among clones, serotypes, and resistance genes.
PMID- 26415874
TI - Preparing pharmacists to deliver a targeted service in hypertension management:
evaluation of an interprofessional training program.
AB - BACKGROUND: Non-adherence to medicines by patients and suboptimal prescribing by
clinicians underpin poor blood pressure (BP) control in hypertension. In this
study, a training program was designed to enable community pharmacists to deliver
a service in hypertension management targeting therapeutic adjustments and
medication adherence. A comprehensive evaluation of the training program was
undertaken. METHODS: Tailored training comprising a self-directed pre-work
manual, practical workshop (using real patients), and practice scenarios, was
developed and delivered by an inter-professional team (pharmacists, GPs).
Supported by practical and written assessment, the training focused on the
principles of BP management, BP measurement skills, and adherence strategies.
Pharmacists' experience of the training (expectations, content, format,
relevance) was evaluated quantitatively and qualitatively. Immediate feedback was
obtained via a questionnaire comprising Likert scales (1 = "very well" to 7 =
"poor") and open-ended questions. Further in-depth qualitative evaluation was
undertaken via semi-structured interviews several months post-training (and post
service implementation). RESULTS: Seventeen pharmacists were recruited, trained
and assessed as competent. All were highly satisfied with the training; other
than the 'amount of information provided' (median score = 5, "just right"), all
aspects of training attained the most positive score of '1'. Pharmacists most
valued the integrated team-based approach, GP involvement, and inclusion of real
patients, as well as the pre-reading manual, BP measurement workshop, and case
studies (simulation). Post-implementation the interviews highlighted that
comprehensive training increased pharmacists' confidence in providing the
service, however, training of other pharmacy staff and patient recruitment
strategies were highlighted as a need in future. CONCLUSIONS: Structured, multi
modal training involving simulated and inter-professional learning is effective
in preparing selected community pharmacists for the implementation of new
services in the context of hypertension management. This training could be
further enhanced to prepare pharmacists for the challenges encountered in
implementing and evaluating services in practice.
PMID- 26415876
TI - MLCT sensitizers in photochemical upconversion: past, present, and potential
future directions.
AB - This treatment highlights the historical development of MLCT sensitizers in
photochemical upconversion while indentifying current state-of-the-art and
exciting opportunities in this arena moving towards the future.
PMID- 26415875
TI - Lymphomatosis cerebri: a rare form of primary central nervous system lymphoma.
Analysis of 7 cases and systematic review of the literature.
AB - BACKGROUND: Primary central nervous system lymphomas may present as diffuse,
nonenhancing infiltrative lesions. This rare variant is termed lymphomatosis
cerebri (LC). We did a systematic review and analysis of the literature, adding
our own cases, to better characterize LC in order to improve early diagnosis and
treatment. METHODS: PubMed, ISI Web of Knowledge, and hospital databases were
reviewed. Information was extracted regarding demographic, clinical,
histological, cerebrospinal fluid (CSF), neuroimaging, and treatment variables.
The impact of single parameters on overall survival (OS) was determined by
applying univariate and multivariate analyses. RESULTS: Forty-two patients were
included (median age: 58 y; range: 28-80 y). At consultation, 52% of patients had
a poor KPS. The most common presenting symptom was cognitive decline (59.5%).
Imaging studies showed supratentorial and infratentorial infiltration in 55% of
patients and bilateral hemispheric involvement in 95%. CSF pleocytosis was
present in 51.5% of the patients. Median time to diagnosis was 4.5 (range: 1-30)
months, and the diagnosis was not established until autopsy for 33% of patients.
The median OS was 2.95 (range: 0.33-56) months; however, those patients who
received methotrexate had a median OS of 13.8 (range: 0.7-56) months. Analysis
identified KPS >= 70 (HR: 0.32; 95% CI: 0.114-0.894; P = .03) and treatment with
methotrexate (HR: 0.19; 95% CI: 0.041-0.886; P = .034) as independent favorable
prognostic factors, whereas T-cell lymphoma was independently related with a
worse outcome (HR: 6.62; 95% CI: 1.317-33.316; P = .022). CONCLUSIONS: LC is a
misdiagnosed entity associated with considerable diagnostic delay. MRI evidence
of bilateral hemispheric involvement and CSF pleocytosis should be alerts for
this diagnosis. Treatment with methotrexate-based chemotherapy must be
considered, especially for patients with good KPS.
PMID- 26415878
TI - Large scale analysis of the mutational landscape in beta-glucuronidase: A major
player of mucopolysaccharidosis type VII.
AB - The lysosomal storage disorders are a group of 50 unique inherited diseases
characterized by unseemly lipid storage in lysosomes. These malfunctions arise
due to genetic mutations that result in deficiency or reduced activities of the
lysosomal enzymes, which are responsible for catabolism of biological
macromolecules. Sly syndrome or mucopolysaccharidosis type VII is a lysosomal
storage disorder associated with the deficiency of beta-glucuronidase (EC
3.2.1.31) that catalyzes the hydrolysis of beta-D-glucuronic acid residues from
the non-reducing terminal of glycosaminoglycan. The effects of the disease
causing mutations on the framework of the sequences and structure of beta
glucuronidase (GUSBp) were analyzed utilizing a variety of bioinformatic tools.
These analyses showed that 211 mutations may result in alteration of the
biological activity of GUSBp, including previously experimentally validated
mutations. Finally, we refined 90 disease causing mutations, which presumably
cause a significant impact on the structure, function, and stability of GUSBp.
Stability analyses showed that mutations p.Phe208Pro, p.Phe539Gly, p.Leu622Gly,
p.Ile499Gly and p.Ile586Gly caused the highest impact on GUSBp stability and
function because of destabilization of the protein structure. Furthermore,
structures of wild type and mutant GUSBp were subjected to molecular dynamics
simulation to examine the relative structural behaviors in the explicit
conditions of water. In a broader view, the use of in silico approaches provided
a useful understanding of the effect of single point mutations on the structure
function relationship of GUSBp.
PMID- 26415877
TI - Downregulating p22phox ameliorates inflammatory response in Angiotensin II
induced oxidative stress by regulating MAPK and NF-kappaB pathways in ARPE-19
cells.
AB - Oxidative stress and inflammation are two interrelated biological events
implicated in the pathogenesis of many diseases. Reactive oxygen species (ROS)
produced under oxidative stress play a key role in pathological conditions.
Inhibition of p22phox, an indispensable component of the NADPH oxidase (NOX)
complex comprising the main source of ROS, plays a protective role in many ocular
conditions by inhibiting the activation of NOXs and the generation of ROS.
However, little is understood regarding the role of p22phox in oxidative stress
related inflammation in the eye. We used a p22phox small interfering RNA (siRNA)
to transfect the retinal pigment epithelium (RPE)-derived cell line ARPE-19, and
human primary RPE (hRPE) cells, then stimulated with Ang II. We observed a potent
anti-inflammatory effect and studied the underlying mechanism. Downregulating
p22phox resulted in decreased ROS generation, a reduction of NOXs (NOX1, 2, 4)
and a decrease in inflammatory cytokine. In addition, p22phox downregulation
reduced the activation of the MAPK and NF-kappaB signaling pathways. We conclude
that inhibition of p22phox has an anti-inflammatory effect in Ang II-induced
oxidative stress. Suppressing the MAPK and NF-kappaB pathways is involved in this
protective effect. These results suggest that p22phox may provide a promising
therapeutic target for oxidative stress-induced ocular inflammation.
PMID- 26415879
TI - MicroRNA-23a regulates 3T3-L1 adipocyte differentiation.
AB - MicroRNAs (miRNAs) are small, non-coding RNAs, which are involved in regulation
of a variety of biological processes. Since previous studies regarding the role
of miRNAs in the regulation of adipogenic differentiation have shown that miRNA
27a, one member of miRNA-23a~27a~24 cluster, could suppress adipogenesis. We now
investigated whether miRNA-23a regulates adipogenic differentiation. In the
present study, we showed that the expression of miRNA-23a is decreased during the
process of adipogenic differentiation. Over-expression of miRNA-23a decreased
lipid accumulation and triglyceride content in 3T3-L1 adipocytes. Our results
also demonstrated that miRNA-23a decreases mRNA levels of adipocyte-specific
genes involved in lipogenic transcription, fatty acid synthesis and fatty acid
transport. These findings suggested miRNA-23a to be a new type of adipogenic
depressor and to play an important role in regulating adipocyte differentiation.
PMID- 26415880
TI - D-dimer levels in maintenance hemodialysis patients: High prevalence of positive
values also in the group without predisposing diseases.
AB - We aimed to estimate the prevalence of elevated D-dimer levels in all chronic
hemodialysis patients and those without additional disease, and to identify
factors associated with increased D-dimer. In 167 chronic hemodialysis patients
from our center, D-dimer was measured before dialysis. The effects of age, C
reactive protein (CRP), recent acute illness, vascular access, anticoagulation
type, dialysis vintage, and chronic diseases, considered to predispose for
increased D-dimer levels, were analyzed. The median D-dimer in the whole group
was 966 (inter-quartile range [IQR] 524-1947) MUg/L and was positive (>500 MUg/L)
in 75% of cases. D-dimer was positive in 91% of patients with acute illness, 76%
of those with predisposing chronic diseases, but was still positive in 52% of
patients without additional disease (i.e., acute illness or predisposing chronic
diseases) - median D-dimer was 538.5 (IQR 359-966) MUg/L. D-dimer was correlated
to patients' age, but not dialysis vintage. In univariate analysis, the D-dimer
levels were significantly higher in patients with atrial fibrillation, ischemic
heart disease, recent acute illness, increased CRP, dialyzed over a catheter, and
on citrate anticoagulation. Multivariate logistic regression showed that only age
>65 years (odds ratio [OR] 2.93), catheter (OR 4.86), and positive CRP (OR 4.07)
were independently associated with positive D-dimer at 500 MUg/L cut-off, while
the significance of age disappeared at 2000 MUg/L cut-off. To conclude, the high
prevalence of positive D-dimer values even in hemodialysis patients without
additional disease limits the use of D-dimer for exclusion of thromboembolic
diseases in hemodialysis patients.
PMID- 26415881
TI - TRPV4 channels: physiological and pathological role in cardiovascular system.
AB - TRPV4 channels are non-selective cation channels permeable to Ca(2+), Na(+), and
Mg(2+) ions. Recently, TRPV4 channels have received considerable attention as
these channels are widely expressed in the cardiovascular system including
endothelial cells, cardiac fibroblasts, vascular smooth muscles, and peri
vascular nerves. Therefore, these channels possibly play a pivotal role in the
maintenance of cardiovascular homeostasis. TRPV4 channels critically regulate
flow-induced arteriogenesis, TGF-beta1-induced differentiation of cardiac
fibroblasts into myofibroblasts, and heart failure-induced pulmonary edema. These
channels also mediate hypoxia-induced increase in proliferation and migration of
pulmonary artery smooth muscle cells and progression of pulmonary hypertension.
These channels also maintain flow-induced vasodilation and preserve vascular
function by directly activating Ca(2+)-dependent KCa channels. Furthermore, these
may also induce vasodilation and maintain blood pressure indirectly by evoking
the release of NO, CGRP, and substance P. The present review discusses the
evidences and the potential mechanisms implicated in diverse responses including
arteriogenesis, cardiac remodeling, congestive heart failure-induced pulmonary
edema, pulmonary hypertension, flow-induced dilation, regulation of blood
pressure, and hypoxic preconditioning.
PMID- 26415883
TI - SDHC methylation in gastrointestinal stromal tumors (GIST): a case report.
AB - BACKGROUND: Gastrointestinal stromal tumors (GIST) recently have been recognized
as a genetically and biologically heterogeneous disease. In addition to KIT or
PDGFRA mutated GIST, mutational inactivation of succinate dehydrogenase (SDH)
subunits has been detected in the KIT/PDGFRA wild-type subgroup, referred to as
SDH deficient (dSDH). Even though most dSDH GIST harbor mutations in SDHx subunit
genes, some are SDHx wild type. Epigenetic regulation by DNA methylation of CpG
islands recently has been found to be an alternative mechanism underlying the
lack of SDH complex in GIST. CASE PRESENTATION: We report a particular case of
dSDH GIST, previously analyzed with microarrays and next-generation sequencing,
for which no molecular pathogenetic events have been identified. Gene expression
analysis showed remarkable down-modulation of SDHC mRNA with respect to all other
GIST samples, both SDHA-mutant and KIT/PDGFRA-mutant GIST. By a bisulfite
methylation assay targeted to 2 SDHC CpG islands, we detected hypermethylation of
the SDHC promoter. CONCLUSION: Herein we report an additional case of dSDH GIST
without SDHx mutation but harboring hypermethylation in the SDHC promoter, thus
confirming the complexity of the molecular background of this subtype of GIST.
PMID- 26415884
TI - A call to arms against "The Phantom of Epilepsy".
PMID- 26415882
TI - Chromatin interaction analysis reveals changes in small chromosome and telomere
clustering between epithelial and breast cancer cells.
AB - BACKGROUND: Higher-order chromatin structure is often perturbed in cancer and
other pathological states. Although several genetic and epigenetic differences
have been charted between normal and breast cancer tissues, changes in higher
order chromatin organization during tumorigenesis have not been fully explored.
To probe the differences in higher-order chromatin structure between mammary
epithelial and breast cancer cells, we performed Hi-C analysis on MCF-10A mammary
epithelial and MCF-7 breast cancer cell lines. RESULTS: Our studies reveal that
the small, gene-rich chromosomes chr16 through chr22 in the MCF-7 breast cancer
genome display decreased interaction frequency with each other compared to the
inter-chromosomal interaction frequency in the MCF-10A epithelial cells.
Interestingly, this finding is associated with a higher occurrence of open
compartments on chr16-22 in MCF-7 cells. Pathway analysis of the MCF-7 up
regulated genes located in altered compartment regions on chr16-22 reveals
pathways related to repression of WNT signaling. There are also differences in
intra-chromosomal interactions between the cell lines; telomeric and sub
telomeric regions in the MCF-10A cells display more frequent interactions than
are observed in the MCF-7 cells. CONCLUSIONS: We show evidence of an intricate
relationship between chromosomal organization and gene expression between
epithelial and breast cancer cells. Importantly, this work provides a genome-wide
view of higher-order chromatin dynamics and a resource for studying higher-order
chromatin interactions in two cell lines commonly used to study the progression
of breast cancer.
PMID- 26415885
TI - Compassion or stigma? How adults bereaved by alcohol or drugs experience
services.
AB - How to promote compassionate care within public services is a concern in several
countries; specifically, some British healthcare scandals highlight poor care for
service users who may readily be stigmatised as 'other'. The article therefore
aims to understand better the relationship between stigma and compassion. As
people bereaved by a drug- or alcohol-related death often experience stigma, the
article draws on findings from a major British study, conducted during 2012-2015
by the authors, of people bereaved in this way, in order to see how service
provision can be improved. One hundred and six bereaved family members were
interviewed in depth about their experiences of loss and support. Thematic
analysis developed theoretical understandings of participants' lived experiences.
This article analyses our data on how bereaved people experienced stigma and
kindness from practitioners of all kinds. We found that stigma can be mitigated
by small acts of kindness from those encountered after the death. Stigma entails
stereotyping, othering and disgust, each of which has emotional and cognitive
aspects; kindness entails identification and fellow feeling; professionalism has
classically entailed emotional detachment, but interviewees found cold
professionalism as disturbing as explicit disgust. Drawing on theories concerning
the end of life, bereavement and emotional labour, the article analyses the
relationship between stigma, kindness and professionalism, and identifies some
strategies to counter stigmatisation and foster compassion.
PMID- 26415886
TI - Validity and reliability of an online extended version of the Nordic
Musculoskeletal Questionnaire (NMQ-E2) to measure nurses' fitness.
AB - AIMS AND OBJECTIVES: To describe modifications to a second extended version of
the Nordic Musculoskeletal Questionnaire for online use in nursing populations,
and check validity and reliability. BACKGROUND: The Nordic Musculoskeletal
Questionnaire has been used to assess the severity and impact of musculoskeletal
symptoms in occupational groups. The reliability of a previous extended version
was established for paper-based, self-administration among nursing students. This
current study extended the questionnaire to collect more information regarding
musculoskeletal symptoms in all nine body regions and their work-relatedness, as
an instrument is needed to gather evidence about the impact of fitness levels on
occupational musculoskeletal disorders among nurses. DESIGN: Psychometric
evaluation. METHOD: Sixty-five undergraduate nurses completed the online extended
Nordic Musculoskeletal Questionnaire twice. Content validity was examined by
expert review and construct validity by exploratory factor analysis of 90
responses from the first completion. Reliability was checked by examining
internal consistency, kappa statistics, proportions of observed, and positive and
negative agreements, intra-class correlation coefficient and standard error of
measurement. RESULTS: The instrument had high internal consistency and
exploratory factor analysis revealed it was a relatively homogenous
(unidimensional) measure of musculoskeletal symptom severity. Age of onset of
symptoms questions were reliable, with high mean intra-class correlation
coefficients and low mean standard errors of measurement. Overall, questions
showed high mean strengths of agreement and proportions of observed agreement:
three-quarters of the prevalence questions and 99% of the severity/impact
questions had 10% or fewer disagreements. CONCLUSIONS: Modifications to the
Nordic Musculoskeletal Questionnaire and online administration did not diminish
its validity or reliability for obtaining information about the severity of
nurses' musculoskeletal symptoms. RELEVANCE TO CLINICAL PRACTICE: Occupational
musculoskeletal disorders are an issue for nurses. This questionnaire can be used
to monitor nurses' musculoskeletal health, and in musculoskeletal disorder
prevention studies.
PMID- 26415888
TI - Controlled release of drugs in electrosprayed nanoparticles for bone tissue
engineering.
AB - Generating porous topographic substrates, by mimicking the native extracellular
matrix (ECM) to promote the regeneration of damaged bone tissues, is a
challenging process. Generally, scaffolds developed for bone tissue regeneration
support bone cell growth and induce bone-forming cells by natural proteins and
growth factors. Limitations are often associated with these approaches such as
improper scaffold stability, and insufficient cell adhesion, proliferation,
differentiation, and mineralization with less growth factor expression.
Therefore, the use of engineered nanoparticles has been rapidly increasing in
bone tissue engineering (BTE) applications. The electrospray technique is
advantageous over other conventional methods as it generates nanomaterials of
particle sizes in the micro/nanoscale range. The size and charge of the particles
are controlled by regulating the polymer solution flow rate and electric voltage.
The unique properties of nanoparticles such as large surface area-to-volume
ratio, small size, and higher reactivity make them promising candidates in the
field of biomedical engineering. These nanomaterials are extensively used as
therapeutic agents and for drug delivery, mimicking ECM, and restoring and
improving the functions of damaged organs. The controlled and sustained release
of encapsulated drugs, proteins, vaccines, growth factors, cells, and nucleotides
from nanoparticles has been well developed in nanomedicine. This review provides
an insight into the preparation of nanoparticles by electrospraying technique and
illustrates the use of nanoparticles in drug delivery for promoting bone tissue
regeneration.
PMID- 26415890
TI - Ion transport and selectivity in biomimetic nanopores with pH-tunable
zwitterionic polyelectrolyte brushes.
AB - Inspired by nature, functionalized nanopores with biomimetic structures have
attracted growing interests in using them as novel platforms for applications of
regulating ion and nanoparticle transport. To improve these emerging
applications, we study theoretically for the first time the ion transport and
selectivity in short nanopores functionalized with pH tunable, zwitterionic
polyelectrolyte (PE) brushes. In addition to background salt ions, the study
takes into account the presence of H(+) and OH(-) ions along with the chemistry
reactions between functional groups on PE chains and protons. Due to ion
concentration polarization, the charge density of PE layers is not homogeneously
distributed and depends significantly on the background salt concentration, pH,
grafting density of PE chains, and applied voltage bias, thereby resulting in
many interesting and unexpected ion transport phenomena in the nanopore. For
example, the ion selectivity of the biomimetic nanopore can be regulated from
anion-selective (cation-selective) to cation-selective (anion-selective) by
diminishing (raising) the solution pH when a sufficiently small grafting density
of PE chains, large voltage bias, and low background salt concentration are
applied.
PMID- 26415889
TI - Phasic stabilization of motor output after auditory and visual distractors.
AB - To maintain steady motor output, distracting sensory stimuli need to be blocked.
To study the effects of brief auditory and visual distractors on the human
primary motor (M1) cortex, we monitored magnetoencephalographic (MEG) cortical
rhythms, electromyogram (EMG) of finger flexors, and corticomuscular coherence
(CMC) during right-hand pinch (force 5-7% of maximum) while 1-kHz tones and
checkerboard patterns were presented for 100 ms once every 3.5-5 s. Twenty-one
subjects (out of twenty-two) showed statistically significant ~20-Hz CMC. Both
distractors elicited a covert startle-like response evident in changes of force
and EMG (~50% of the background variation) but without any visible movement,
followed by ~1-s enhancement of CMC (auditory on average by 75%, P < 0.001;
visual by 33%, P < 0.05) and rolandic ~20-Hz rhythm (auditory by 14%, P < 0.05;
visual by 11%, P < 0.01). Directional coupling of coherence from muscle to the M1
cortex (EMG->MEG) increased for ~0.5 s at the onset of the CMC enhancement, but
only after auditory distractor (by 105%; P < 0.05), likely reflecting startle
related proprioceptive afference. The 20-Hz enhancements occurred in the left M1
cortex and were for the auditory stimuli preceded by an early suppression (by 7%,
P < 0.05). Task-unrelated distractors modulated corticospinal coupling at ~20 Hz.
We propose that the distractors triggered covert startle-like responses,
resulting in proprioceptive afference to the cortex, and that they also
transiently disengaged the subject's attention from the fine-motor task. As a
result, the corticospinal output was readjusted to keep the contraction force
stable.
PMID- 26415887
TI - The role of fatty acids in insulin resistance.
AB - Insulin resistance is a multi-faceted disruption of the communication between
insulin and the interior of a target cell. The underlying cause of insulin
appears to be inflammation that can either be increased or decreased by the fatty
acid composition of the diet. However, the molecular basis for insulin resistance
can be quite different in various organs. This review deals with various types of
inflammatory inputs mediated by fatty acids, which affect the extent of insulin
resistance in various organs.
PMID- 26415891
TI - Validation and utilization of a TFE3 break-apart FISH assay for Xp11.2
translocation renal cell carcinoma and alveolar soft part sarcoma.
AB - BACKGROUND: Xp11.2 or TFE3 translocation renal cell carcinomas (RCC) and alveolar
soft part sarcoma (ASPS) are characterized by chromosome translocations involving
the Xp11.2 breakpoint resulting in transcription factor TFE3 gene fusions. The
most common translocations documented in TFE3 RCCs are t(X;1) (p11.2;q21) and
t(X;17) (p11.2;q25) which leads to fusion of TFE3 gene on Xp11.2 with PRCC or
ASPL respectively. TFE3 immunohistochemistry (IHC) has been inconsistent over
time due to background staining problems in part related to fixation issues.
Karyotyping to detect TFE3 gene rearrangement requires typically unavailable
fresh tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) is
generally very challenging due to degradation of RNA in archival material. The
study objective was to develop and validate a TFE3 break-apart fluorescence in
situ hybridization (FISH) assay to confirm Xp11 translocation RCCs and ASPS.
METHODS: Representative sections of formalin-fixed paraffin-embedded tissue
blocks were selected in 40 possible cases. Approximately 60 tumor cells were
analyzed in the targeted region. The validation of TFE3 FISH was done with 11
negative and two positive cases. Cut off for a positive result was validated as
>7.15 % positive nuclei with any pattern of break-apart signals. FISH evaluation
was done blinded of the immunohistochemical or karyotype data. RESULTS: Three out
of forty cases were positive for the TFE3 break-apart signals by FISH. The
negative cases were reported as clear cell RCC with papillary features (10),
clear cell RCC with sarcomatoid areas (2), Papillary RCC with clear cell areas
(9), Chromophobe RCC (2), RCC, unclassified type (3) and renal medullary
carcinoma (1). 3 of the negative cases were consultation cases for renal tumor
with unknown histology. Seven negative cases were soft tissue tumor suspicious
for ASPS. CONCLUSION: Our study validates the utility of TFE3 break-apart FISH on
formalin-fixed paraffin-embedded tissue sections for diagnosis and confirmation
of Xp11.2 translocation RCCs and ASPS.
PMID- 26415894
TI - Proteomics of the Roseobacter clade, a window to the marine microbiology
landscape.
AB - Oceans are powered by metabolically-active microorganisms which are main drivers
of global biogeochemical cycles on Earth. A decade ago, marine microbiology was
boosted with next-generation sequencing capacities and the launch of large
metagenomics surveys. High-performing proteomics is now comprehensive enough for
reaching genome-wide and systems-wide scales. It is highly complementary to
transcriptomics in order to analyze functional dynamics of marine microbes and
microbial complex systems. Next-generation proteomics allows new perspectives for
better understanding microbial lifestyles and uncovering the complexity of
microbial communities. Here, we review the proteomics approaches and outcomes of
recent work carried out on one of the most thoroughly studied marine generalist
microorganisms, i.e. the Roseobacter clade, as pivotal examples. We also discuss
how the study of the proteome of these organisms has helped in the understanding
of the ecological strategy and lifestyle of this relevant marine clade, not only
in laboratory cultures but also in its natural environment.
PMID- 26415893
TI - Challenges in detection and treatment of multidrug resistant tuberculosis
patients in Vietnam.
AB - BACKGROUND: Vietnam is ranked 14(th) among 27 countries with high burden of
multidrug-resistant tuberculosis (MDR-TB). In 2009, the Vietnamese government
issued a policy on MDR-TB called Programmatic Management of Drug-resistant
Tuberculosis (PMDT) to enhance and scale up diagnosis and treatment services for
MDR-TB. Here we assess the PMDT performance in 2013 to determine the challenges
to the successful identification and enrollment for treatment of MDR-TB in
Vietnam. METHODS: In 35 provinces implementing PMDT, we quantified the number of
MDR-TB presumptive patients tested for MDR-TB by Xpert MTB/RIF and the number of
MDR-TB patients started on second-line treatment. In addition, existing reports
and documents related to MDR-TB policies and guidelines in Vietnam were reviewed,
supplemented with focus group discussions and in-depth interviews with MDR-TB key
staff members. RESULTS: 5,668 (31.2 %) of estimated 18,165 MDR-TB presumptive
cases were tested by Xpert MTB/RIF and second-line treatment was provided to 948
out of 5100 (18.7 %) of MDR-TB patients. Those tested for MDR-TB were 340/3224
(10.5 %) of TB-HIV co-infected patients and 290/2214 (13.1 %) of patients who
remained sputum smear-positive after 2 and 3 months of category I TB regimen.
Qualitative findings revealed the following challenges to detection and
enrollment of MDR-TB in Vietnam: insufficient TB screening capacity at district
hospitals where TB units were not available and poor communication and
implementation of policy changes. Instructions for policy changes were not always
received, and training was inconsistent between training courses. The private
sector did not adequately report MDR-TB cases to the NTP. CONCLUSIONS: The
proportion of MDR-TB patients diagnosed and enrolled for second-line treatment is
less than 20 % of the estimated total. The low enrollment is largely due to the
fact that many patients at risk are missed for MDR-TB screening. In order to
detect more MDR-TB cases, Vietnam should intensify case finding of MDR-TB by a
comprehensive strategy to screen for MDR-TB among new cases rather than targeting
previously treated cases, in particular those with HIV co-infection and contacts
of MDR-TB patients, and should engage the private sector in PMDT.
PMID- 26415895
TI - Evaluating the use of plerixafor in stem cell mobilisation - an economic analysis
of the PHANTASTIC trial.
AB - Plerixafor is an effective haematopoietic stem cell mobilising agent in
candidates for autologous transplantation, including patients with myeloma and
lymphoma. Here we compare 98 plerixafor recipients in the PHANTASTIC trial with
151 historic controls mobilised by conventional chemotherapy (each with
granulocyte colony-stimulating factor, G-CSF). Seventy (71.4%) plerixafor
mobilised patients achieved the composite primary endpoint of >=4 * 10(6) CD34+
cells kg(-1) in <=2 aphereses and no clinically significant neutropenia, compared
to 48 (31.8%) historic controls (P < 0.001), and this significant advantage was
maintained in scenario analyses testing components of this composite endpoint. A
patient-level cost analysis was undertaken for 249 patients, which included the
cost of remobilising patients where initial mobilisation had failed. Combined
mean treatment cost for plerixafor mobilised patients was L12,679 compared with
L11,694 for historical controls. However, plerixafor produces an average saving
of L3,828 per lymphoma patient but average cost increase by L5,245 per myeloma
patient. The present data demonstrate cost-effectiveness for plerixafor as a
first line mobilisation agent, certainly for lymphoma patients, where substantial
resource savings and achievement of the primary endpoint are likely. J. Clin.
Apheresis 31:434-442, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26415892
TI - Prior human polyomavirus and papillomavirus infection and incident lung cancer: a
nested case-control study.
AB - PURPOSE: To test whether infection with select human polyomaviruses (HPyV) and
human papillomaviruses (HPV) is associated with incident lung cancer. METHODS: We
performed a nested case-control study, testing serum from the carotene and
retinol efficacy trial, conducted 1985-2005, for antibodies to Merkel cell (MCV),
KI (KIV), and WU (WUV) HPyVs as well as to six high-risk and two low-risk HPV
types. Incident lung cancer cases (n = 200) were frequency-matched with controls
(n = 200) on age, enrollment and blood draw dates, intervention arm assignment,
and the number of serum freeze/thaw cycles. Sera were tested using multiplex
liquid bead microarray antibody assays. We used logistic regression to assess the
association between HPyV and HPV antibodies and lung cancer. RESULTS: There was
no evidence of a positive association between levels of MCV, KIV, or WUV
antibodies and incident lung cancer (p corrected >0.10 for all trend tests; odds
ratio (OR) range 0.72-1.09, p corrected >0.10 for all). There was also no
evidence for a positive association between HPV 16 or 18 infection and incident
lung cancer (p corrected >=0.10 for all trend tests; OR range 0.25-2.54, p > 0.05
for all OR > 1), but the number of persons with serologic evidence of these
infections was small. CONCLUSIONS: Prior infection with any of several types of
HPyV or HPV was not associated with subsequent diagnosis of lung cancer.
Infection with these viruses likely does not influence a person's risk of lung
cancer in Western smoking populations.
PMID- 26415896
TI - Quantitative evaluation of positive phi angle propensity in flexible regions of
proteins from three-bond J couplings.
AB - (3)JHNHalpha and (3)JC'C' couplings can be readily measured in isotopically
enriched proteins and were shown to contain precise information on the backbone
torsion angles, phi, sampled in disordered regions of proteins. However,
quantitative interpretation of these couplings required the population of
conformers with positive phi angles to be very small. Here, we demonstrate that
this restriction can be removed by measurement of (3)JC'Halpha values. Even
though the functional forms of the (3)JC'Halpha and (3)JHNHalpha Karplus
equations are the same, large differences in their coefficients enable accurate
determination of the fraction of time that positive phi angles are sampled. A
four-dimensional triple resonance HACANH[C'] E.COSY experiment is introduced to
simultaneously measure (3)JC'Halpha and (3)JHNC' in the typically very congested
spectra of disordered proteins. High resolution in these spectra is obtained by
non-uniform sampling (in the 0.1-0.5% range). Application to the intrinsically
disordered protein alpha-synuclein shows that while most residues have close-to
zero positive phi angle populations, up to 16% positive phi population is
observed for Asn residues. Positive phi angle populations determined with the new
approach agree closely with consensus values from protein coil libraries and
prior analysis of a large set of other NMR parameters. The combination of
(3)JHNC' and (3)JC'C' provides information about the amplitude of phi angle
dynamics.
PMID- 26415898
TI - Dysferlin deficiency blunts beta-adrenergic-dependent lusitropic function of
mouse heart.
AB - Dysferlin is a cell membrane bound protein with a role in the repair of skeletal
and cardiac muscle cells. Deficiency of dysferlin leads to limb-girdle muscular
dystrophy 2B (LGMD2B) and Miyoshi myopathy. In cardiac muscle, dysferlin is
located at the intercalated disc and transverse tubule membranes. Loss of
dysferlin causes death of cardiomyocytes, notably in ageing hearts, leading to
dilated cardiomyopathy and heart failure in LGM2B patients. To understand the
primary pathogenesis and pathophysiology of dysferlin cardiomyopathy, we studied
cardiac phenotypes of young adult dysferlin knockout mice and found early
myocardial hypertrophy with largely compensated baseline cardiac function.
Cardiomyocytes isolated from dysferlin-deficient mice showed normal shortening
and re-lengthening velocities in the absence of external load with normal peak
systolic Ca(2+) but slower Ca(2+) re-sequestration than wild-type controls. The
effects of isoproterenol on relaxation velocity, left ventricular systolic
pressure and stroke volume were blunted in dysferlin-deficient mouse hearts
compared with that in wild-type hearts. Young dysferlin-deficient mouse hearts
expressed normal isoforms of myofilament proteins whereas the phosphorylation of
ventricular myosin light chain 2 was significantly increased, implying a
molecular response to the impaired lusitropic function. These early phenotypes of
diastolic cardiac dysfunction and blunted lusitropic response of cardiac muscle
to beta-adrenergic stimulation indicate a novel pathogenic mechanism of dysferlin
cardiomyopathy.
PMID- 26415897
TI - The effects of stimulus complexity on the preattentive processing of self
generated and nonself voices: An ERP study.
AB - The ability to differentiate one's own voice from the voice of somebody else
plays a critical role in successful verbal self-monitoring processes and in
communication. However, most of the existing studies have only focused on the
sensory correlates of self-generated voice processing, whereas the effects of
attentional demands and stimulus complexity on self-generated voice processing
remain largely unknown. In this study, we investigated the effects of stimulus
complexity on the preattentive processing of self and nonself voice stimuli.
Event-related potentials (ERPs) were recorded from 17 healthy males who watched a
silent movie while ignoring prerecorded self-generated (SGV) and nonself (NSV)
voice stimuli, consisting of a vocalization (vocalization category condition:
VCC) or of a disyllabic word (word category condition: WCC). All voice stimuli
were presented as standard and deviant events in four distinct oddball sequences.
The mismatch negativity (MMN) ERP component peaked earlier for NSV than for SGV
stimuli. Moreover, when compared with SGV stimuli, the P3a amplitude was
increased for NSV stimuli in the VCC only, whereas in the WCC no significant
differences were found between the two voice types. These findings suggest
differences in the time course of automatic detection of a change in voice
identity. In addition, they suggest that stimulus complexity modulates the
magnitude of the orienting response to SGV and NSV stimuli, extending previous
findings on self-voice processing.
PMID- 26415899
TI - Evaluation of conjunctival swab sampling in the diagnosis of canine
leishmaniasis: A two-year follow-up study in Cukurova Plain, Turkey.
AB - The diagnosis of canine leishmaniasis (CanL) in symptomatic and asymptomatic dogs
is a very important and problematic public health issue in Turkey. A longitudinal
study was carried out on dogs in selected villages in the Cukurova Plain in
Turkey, from July 2011 to June 2013, where cutaneous (CL) and visceral (VL)
leishmaniasis is endemic. The study aimed to determine the prevalence of CanL and
to evaluate the early diagnostic performance of the non-invasive conjunctival
swab nested PCR (CS n-PCR) test in comparison with the Indirect Fluorescent
Antibody Test (IFAT). The consecutive blood and CS samples from a representative
number of dogs (80-100 dogs/each survey) were collected in a cohort of 6 villages
located in the area. Clinical symptoms, demographic and physical features about
each dog were noted and lymph node aspiration samples were obtained from selected
dogs with lymphadenopathy. In four surveys during the period, a total of 338 sets
(blood and CS) of samples from 206 dogs were obtained, such that 83 dogs were
sampled more than once. In the cross-sectional analysis, the CanL prevalence was
found to be 27.18% (between 7.14% and 39.13%) by IFAT and 41.74% (between 29.03%
and 46.66%) by CS n-PCR. The isolated strains were identified as Leishmania
infantum MON-1 (n=9) and MON-98 (n=2) by MLEE analysis. Genetic studies targeting
the Hsp70 and ITS1 regions performed on 11 dog isolates also showed two clear
separate groups. According to IFAT results, 24 of the 83 dogs sampled more than
once showed seroconversion (n=19) or a four-fold increase in Ab titers (n=5),
while 17 were positive in the initial screening. Forty-two dogs stayed negative
during the whole period. The natural Leishmania exposure rate was detected as
31.14% in the study area. CS n-PCR only detected Leishmania infection earlier
than IFAT in 8 dogs. No statistical difference was found after the analysis of
demographical and physical data. The results indicated that (i) circulation of
the dog population is very common in settlements in the Cukurova Plain, but the
disease prevalence is high and stable, (ii) the performance of CS n-PCR for
detecting Leishmania-dog contact is higher than IFAT, (iii) and some of the
parasites isolated from dogs have different zymodemes and/or genotypes from
previous human and sand fly isolates; suggesting the probability of two different
cycles of leishmaniasis in this particular area. This hypothesis should be
supported by future studies targeting vectors and reservoirs.
PMID- 26415900
TI - Heterotrophic bacteria from an extremely phosphate-poor lake have conditionally
reduced phosphorus demand and utilize diverse sources of phosphorus.
AB - Heterotrophic Proteobacteria and Actinobacteria were isolated from Lake Matano,
Indonesia, a stratified, ferruginous (iron-rich), ultra-oligotrophic lake with
phosphate concentrations below 50 nM. Here, we describe the growth of eight
strains of heterotrophic bacteria on a variety of soluble and insoluble sources
of phosphorus. When transferred to medium without added phosphorus (P), the
isolates grow slowly, their RNA content falls to as low as 1% of cellular dry
weight, and 86-100% of the membrane lipids are replaced with amino- or
glycolipids. Similar changes in lipid composition have been observed in marine
photoautotrophs and soil heterotrophs, and similar flexibility in phosphorus
sources has been demonstrated in marine and soil-dwelling heterotrophs. Our
results demonstrate that heterotrophs isolated from this unusual environment
alter their macromolecular composition, which allows the organisms to grow
efficiently even in their extremely phosphorus-limited environment.
PMID- 26415901
TI - Depression--An emerging indication for botulinum toxin treatment.
AB - The treatment of glabellar frown lines with botulinum toxin injection is one of
the most prevalent procedures in esthetic medicine. It is possible that the
popularity of this intervention is not only owing to its cosmetic effect but also
to modulatory effects on mood and affectivity. Recently, a series of studies
including three randomized controlled trials have consistently shown that such
effects can be used in the treatment of depression. Predominantly female patients
suffering from partly chronic and treatment resistant unipolar depression
experienced a quick, strong and sustained improvement in depressive symptoms
after a single glabellar treatment with botulinum toxin A as a sole or adjunctive
therapy. If these findings are further corroborated in additional studies, the
ever-growing spectrum of applications for botulinum toxin may spread into the
field of psychiatry, showing that the superficial paralysis of facial muscles
may, probably via proprioceptive feedback mechanisms, have profound effects on
the emotional brain.
PMID- 26415902
TI - Characterizing Tityus discrepans scorpion venom from a fractal perspective: Venom
complexity, effects of captivity, sexual dimorphism, differences among species.
AB - A characteristic of venom elution patterns, shared with many other complex
systems, is that many their features cannot be properly described with
statistical or euclidean concepts. The understanding of such systems became
possible with Mandelbrot's fractal analysis. Venom elution patterns were produced
using the reversed phase high performance liquid chromatography (HPLC) with 1 mg
of venom. One reason for the lack of quantitative analyses of the sources of
venom variability is parametrizing the venom chromatograms' complexity. We
quantize this complexity by means of an algorithm which estimates the
contortedness (Q) of a waveform. Fractal analysis was used to compare venoms and
to measure inter- and intra-specific venom variability. We studied variations in
venom complexity derived from gender, seasonal and environmental factors,
duration of captivity in the laboratory, technique used to milk venom.
PMID- 26415903
TI - Induction of IL-12 from human monocytes after stimulation with Androctonus
crassicauda scorpion venom.
AB - The objective of this study was to evaluate the capacity of venom from
Androctonus crassicauda to induce expression/production of interleukin (IL)-12 by
isolated human monocytes. For this purpose, isolated human monocytes were exposed
to different concentrations of the venom (0.16-20 MUg/ml) for varying periods (6,
12, and 24 h). Apart from measures of venom cytotoxicity (i.e., lactase
dehydrogenase activity [LDH] release), measures of IL-12 p40 mRNA (by Real-time
PCR) of IL-12 release (by ELISA) were performed. The results showed that the
venom produced significant concentration- and duration of incubation-dependent
cytotoxicity. Expression of IL-12 p40 mRNA was significantly increased at all
exposure timepoints relative to that in unexposed cells, but was maximal after 6
h of exposure. At that timepoint, the effect from a dose of 2.5 MUg venom/ml
provided the maximal increase among all doses tested. At the level of the protein
itself, IL-12 production remained almost consistently elevated (vs. unexposed
control values) across all exposure timepoints, with the greatest formation again
occurring after 6 h of incubation at a dose of 2.5 MUg venom/ml. The findings
from this study demonstrated that venom from the A. crassicauda scorpion
contained active constituents that could induce a sustained activation of human
monocytes that was manifested, in part, as promotion of the expression/production
of IL-12.
PMID- 26415904
TI - Evaluation of the preclinical efficacy of four antivenoms, distributed in sub
Saharan Africa, to neutralize the venom of the carpet viper, Echis ocellatus,
from Mali, Cameroon, and Nigeria.
AB - Snakebite envenoming causes a heavy toll in sub-Saharan Africa in terms of
mortality and sequelae. In the West African savannah, the viperid Echis ocellatus
is responsible for the vast majority of bites. In the last decades, several new
antivenoms have been introduced for the treatment of these envenomings, although
the assessment of their preclinical efficacy against the venom of E. ocellatus
has been studied only for some of them. This work analyzed comparatively the
ability of four antivenoms (FAV Afrique, EchiTAb G, EchiTAB-Plus-ICP((r)), and
InoserpTM Panafricain) to neutralize lethal, hemorrhagic, and in vitro coagulant
activities of the venoms of E. ocellatus from Mali, Cameroon, and Nigeria. In
addition, an immunoaffinity chromatography antivenomic protocol was used to
assess the ability of the four antivenoms to bind to the proteins of these
venoms. Results showed that all the antivenoms were effective in the
neutralization of the three effects investigated, and were able to immunocapture,
completely or partially, the most abundant components in the E. ocellatus venoms
from the geographical origins sampled. Our observations also highlighted
quantitative differences between antivenoms in their neutralizing and
antivenomics profiles, especially regarding neutralization of in vitro coagulant
activity, suggesting that different doses of these antivenoms are probably needed
for an effective treatment of human envenomings by this species.
PMID- 26415905
TI - The non-competitive blockade of GABAA receptors by an aqueous extract of water
hemlock (Cicuta douglasii) tubers.
AB - Water hemlocks (Cicuta spp.) are acutely toxic members of the Umbellierae family;
the toxicity is due to the presence of C17-polyacetylenes such as cicutoxin.
There is only limited evidence of noncompetitive antagonism by C17-polyacetylenes
at GABAA receptors. In this work with WSS-1 cells, we documented the
noncompetitive blockade of GABAA receptors by an aqueous extract of water hemlock
(Cicuta douglasii) and modulated the actions of the extract with a pretreatment
of 10 MUM midazolam.
PMID- 26415906
TI - Differences in potency and categorical agreement between colistin and polymyxin B
when testing 15,377 clinical strains collected worldwide.
AB - Gram-negative bacilli (n=15,377) were tested against colistin (polymyxin E) and
polymyxin B by a commercial broth microdilution method (Sensititre(r)). Among
Pseudomonas aeruginosa and Acinetobacter spp., colistin and polymyxin B MIC
values were within +/-1 doubling dilution for >99.0% of strains. Among Klebsiella
spp. and Escherichia coli, 55.0 and 53.2% of strains displayed a colistin MIC 2
fold lower than polymyxin B, but polymyxin B was slightly more potent than
colistin against strains with decreased susceptibility to either polymyxin.
PMID- 26415907
TI - Tuning all-Optical Analog to Electromagnetically Induced Transparency in nanobeam
cavities using nanoelectromechanical system.
AB - We report the observations of all-optical electromagnetically induced
transparency in nanostructures using waveguide side-coupled with photonic crystal
nanobeam cavities, which has measured linewidths much narrower than individual
resonances. The quality factor of transparency resonance can be 30 times larger
than those of measured individual resonances. When the gap between cavity and
waveguide is reduced to 10 nm, the bandwidth of destructive interference region
can reach 10 nm while the width of transparency resonance is 0.3 nm.
Subsequently, a comb-drive actuator is introduced to tune the line shape of the
transparency resonance. The width of the peak is reduced to 15 pm and the
resulting quality factor exceeds 10(5).
PMID- 26415908
TI - Genetics affect lung disease and smoking behaviour, study finds.
PMID- 26415909
TI - Na(+) diffusion kinetics in nanoporous metal-hexacyanoferrates.
AB - Metal-hexacyanoferrates (metal-HCFs) are promising candidates for cathode
materials of sodium-ion secondary batteries (SIBs). Here, we systematically
investigated Na(+) diffusion constants (D) and the activation energies (Ea) of
metal-HCFs against the framework size (= a/2). We found that the magnitude of D
(Ea) systematically increases (decreases) with increases in a, indicating that
steric hindrance plays a dominant role in Na(+) diffusion.
PMID- 26415910
TI - In vitro Differentiation of Germ Cells from Stem Cells.
AB - Stem cells are unique cell types with the ability of self-renewal and
differentiation, which mainly include embryonic stem cells, induced pluripotent
stem cells, and adult stem cells. Recently, several research groups have reported
that stem cells can differentiate into germ cells under appropriate conditions in
vitro. Advances in this field have revealed new perspectives for reproductive and
regenerative medicine. Here, we review the progress of in vitro gamete production
from stem cells.
PMID- 26415911
TI - microRNAs and Molecular Pathogenesis of Microcephaly.
AB - Microcephaly is a clinical condition defined as a reduction in head circumference
and brain volume. The abnormal brain size may result from pathological neural
stem cell (NSC) proliferation, survival, differentiation and migration during the
development of the cerebral cortex. This process is controlled by many factors,
including microRNAs that normally silence target genes at the posttranscriptional
level. In this review, we will discuss the roles of microRNAs involved in
different stages of the cortical development to shed light on the pathogenesis of
microcephaly. Understanding the molecular mechanisms of microRNA-mediated
cortical development may help develop a means of microRNA-based diagnosis and
treatment for microcephaly in humans.
PMID- 26415912
TI - Mesenchymal Stem Cells and Cell Therapy for Bone Repair.
AB - Mesenchymal stem cells (MSCs) represent a new therapeutic paradigm for a number
of diseases because they possess unique biological characteristics such as
multipotency, immunomodulation and production of cytokines. Currently, 425 MSC
based clinical trials have been conducted for at least 12 kinds of pathological
conditions, with many completed trials demonstrating the safety and efficacy of
MSCs. Here, we provide an overview of the clinical status of MSCs by searching
the public clinical trials database http://clinicaltrials.gov. Particularly, the
role of MSCs in clinical trials to treat bone defects and injuries is
highlighted.
PMID- 26415913
TI - Stem Cell Therapy and Immunological Rejection in Animal Models.
AB - With their capability to undergo unlimited self-renew and to differentiate into
various functional cells, human pluripotent stem cells, including embryonic stem
cells (hESCs) and induced pluripotent stem cells (hiPSCs), hold great promise in
regenerative medicine to treat currently incurable diseases. Significant progress
has been achieved in differentiating pluripotent stem cells into various
functional cells, such as pancreatic beta cells, neural cells, hepatocytes, and
cardiomyocytes. In addition, three hESC-based therapies to treat spinal cord
injury, macular degeneration and type 1 diabetes have entered clinical trial.
However, there remain several major bottlenecks that hinder the clinical trial of
stem cell based therapy. One such key challenge is the immune rejection of cells
derived from allogeneic hESCs. The challenge of immune rejection is mitigated by
recent discovery of iPSCs, raising the hope that patient-specific hiPSCs can be
differentiated into autologous cells for transplantation into the same patient
without the concern of immune rejection. However, due to the oncogenic potential
of the reprogramming factors and the reprogramming- induced DNA damage, there
remain safety concerns about the cancer risk and immunogenicity of hiPSC-derived
cells. This review discusses recent progress in our understanding of the
immunogenicity of pluripotent stem cells and the development of new strategies to
resolve this challenge.
PMID- 26415914
TI - Inhalable, large porous PLGA microparticles loaded with paclitaxel: preparation,
in vitro and in vivo characterization.
AB - Large porous particles (LPPs) could be used as a useful carrier for non-invasive
delivery to the deep lung. Pulmonary delivery of paclitaxel-loaded LPPs (PTX
LPPs) can help to eliminate the highly complicated and harmful solvent used in
PTX parenteral formulations. PTX-LPPs with mass median aerodynamic diameter
(MMAD) of 5.74 +/- 0.09 MUm, high encapsulation efficiency and good
aerosolisation properties were produced using ammonium bicarbonate as porogen.
Cytotoxicity of PTX-LPPs on A549 and Calu-6 cell lines was comparable with Free
PTX. Endotracheal administration of PTX-LPPs in rats exhibited PTX plasma
concentration in the therapeutic range which lasted 4-fold longer than i.v.
injection. The bioavailability was measured as 51 +/- 7.1%. The lung targeting
efficiency (Te) of PTX-LPPs was 11.9-fold higher than i.v. administration. PTX
LPPs could deliver a higher PTX to lung with a non-toxic plasma level in a longer
duration which shows their pulmonary delivery suitability.
PMID- 26415915
TI - Liking, salt taste perception and use of table salt when consuming reduced-salt
chicken stews in light of South Africa's new salt regulations.
AB - This study investigated the impact of salt reduction on liking, salt taste
perception, and use of table salt when consuming chicken stew in light of South
Africa's new salt recommendations. In total, 432 South-African consumers (aged
35.2 +/- 12.3 years) consumed a full portion of a chicken stew meal once at a
central location. Four stock cube powders varying in salt content were used to
prepare chicken stews: 1) no reduction - 2013 Na level; regular salt level as
currently available on the South African market (24473 mg Na/100 g), 2) salt
reduction smaller than 2016 level, i.e. 10%-reduced (22025 mg Na/100 g), 3) 2016
salt level, as per regulatory prescriptions (18000 mg Na/100 g), 4) 2019 salt
level, as per regulatory prescriptions (13000 mg Na/100 g). Consumers were
randomly allocated to consume one of the four meals. Liking, salt taste
perception, and use of table salt and pepper were measured. Chicken stews
prepared with reduced-salt stock powders were equally well-liked as chicken stews
with the current salt level. Moreover, a gradual reduction of the salt in the
chicken stews resulted in a reduced salt intake, up to an average of 19% for the
total group compared to the benchmark 2013 Na level stew. However, 19% of
consumers compensated by adding salt back to full compensation in some cases.
More salt was added with increased reductions of salt in the meals, even to the
point of full compensation. Further investigation into the impacts of nutrition
communication and education about salt reduction on salt taste perception and use
is needed. This research provides new consumer insights on salt use and
emphasises the need for consumer-focused behaviour change approaches, in addition
to reformulation of products.
PMID- 26415916
TI - Thinking about quantity: the intertwined development of spatial and numerical
cognition.
AB - There are many continuous quantitative dimensions in the physical world.
Philosophical, psychological, and neural work has focused mostly on space and
number. However, there are other important continuous dimensions (e.g., time and
mass). Moreover, space can be broken down into more specific dimensions (e.g.,
length, area, and density) and number can be conceptualized discretely or
continuously (i.e., natural vs real numbers). Variation on these quantitative
dimensions is typically correlated, e.g., larger objects often weigh more than
smaller ones. Number is a distinctive continuous dimension because the natural
numbers (i.e., positive integers) are used to quantify collections of discrete
objects. This aspect of number is emphasized by teaching of the count word
sequence and arithmetic during the early school years. We review research on
spatial and numerical estimation, and argue that a generalized magnitude system
is the starting point for development in both domains. Development occurs along
several lines: (1) changes in capacity, durability, and precision, (2)
differentiation of the generalized magnitude system into separable dimensions,
(3) formation of a discrete number system, i.e., the positive integers, (4)
mapping the positive integers onto the continuous number line, and (5) acquiring
abstract knowledge of the relations between pairs of systems. We discuss
implications of this approach for teaching various topics in mathematics,
including scaling, measurement, proportional reasoning, and fractions.
PMID- 26415917
TI - Bio-Derived, Binderless, Hierarchically Porous Carbon Anodes for Li-ion
Batteries.
AB - Here we explore the electrochemical performance of pyrolyzed skins from the
species A. bisporus, also known as the Portobello mushroom, as free-standing,
binder-free, and current collector-free Li-ion battery anodes. At temperatures
above 900 degrees C, the biomass-derived carbon nanoribbon-like architectures
undergo unique processes to become hierarchically porous. During heat-treatment,
the oxygen and heteroatom-rich organics and potassium compounds naturally present
in the mushroom skins play a mutual role in creating inner void spaces throughout
the resulting carbon nanoribbons, which is a process analogous to KOH-activation
of carbon materials seen in literature. The pores formed in the pyrolytic carbon
nanoribbons range in size from sub-nanometer to tens of nanometers, making the
nanoribbons micro, meso, and macroporous. Detailed studies were conducted on the
carbon nanoribbons using SEM and TEM to study morphology, as well as XRD and EDS
to study composition. The self-supporting nanoribbon anodes demonstrate
significant capacity increase as they undergo additional charge/discharge cycles.
After a pyrolysis temperature of 1100 degrees C, the pristine anodes achieve
over 260 mAh/g after 700 cycles and a Coulombic efficiency of 101.1%, without the
use of harmful solvents or chemical activation agents.
PMID- 26415918
TI - Emergency department syndromic surveillance providing early warning of seasonal
respiratory activity in England.
AB - Seasonal respiratory infections place an increased burden on health services
annually. We used a sentinel emergency department syndromic surveillance system
to understand the factors driving respiratory attendances at emergency
departments (EDs) in England. Trends in different respiratory indicators were
observed to peak at different points during winter, with further variation
observed in the distribution of attendances by age. Multiple linear regression
analysis revealed acute respiratory infection and bronchitis/bronchiolitis ED
attendances in patients aged 1-4 years were particularly sensitive indicators for
increasing respiratory syncytial virus activity. Using near real-time
surveillance of respiratory ED attendances may provide early warning of increased
winter pressures in EDs, particularly driven by seasonal pathogens. This
surveillance may provide additional intelligence about different categories of
attendance, highlighting pressures in particular age groups, thereby aiding
planning and preparation to respond to acute changes in EDs, and thus the health
service in general.
PMID- 26415921
TI - [Castleman's disease: Rapid desensitization for hypersensitivity reaction to
rituximab].
AB - INTRODUCTION: Rapid desensitization allows secure administration of a drug and is
indicated when there is no therapeutic alternative. CASE REPORT: We report a 49
year-old patient who presented with a hypersensitivity reaction following an
infusion of rituximab (375mg/m(2)) in the context of a Castleman's syndrome.
After a clinical flare (splenomegaly, adenopathies) despite treatment with
tocilizumab, anakinra and valganciclovir, the reintroduction of rituximab was
decided, according to the rapid desensitization protocol. Four full dose
desensitizations were successfully performed allowing immediate clinical
improvement (apyrexia, loss of sweating and lymphadenopathy, splenomegaly partial
regression) and biological (negativation of HHV8 viral load, and disappearance of
neutropenia, anemia and thrombocytopenia). CONCLUSION: Rapid desensitization is a
promising method for the pursuit of rituximab therapy after a hypersensitivity
reaction and should be considered in patients with no acceptable therapeutic
alternative.
PMID- 26415919
TI - Epilepsy priorities in Europe: A report of the ILAE-IBE Epilepsy Advocacy Europe
Task Force.
AB - The European Forum on Epilepsy Research (ERF2013), which took place in Dublin,
Ireland, on May 26-29, 2013, was designed to appraise epilepsy research
priorities in Europe through consultation with clinical and basic scientists as
well as representatives of lay organizations and health care providers. The
ultimate goal was to provide a platform to improve the lives of persons with
epilepsy by influencing the political agenda of the EU. The Forum highlighted the
epidemiologic, medical, and social importance of epilepsy in Europe, and
addressed three separate but closely related concepts. First, possibilities were
explored as to how the stigma and social burden associated with epilepsy could be
reduced through targeted initiatives at EU national and regional levels. Second,
ways to ensure optimal standards of care throughout Europe were specifically
discussed. Finally, a need for further funding in epilepsy research within the
European Horizon 2020 funding programme was communicated to politicians and
policymakers participating to the forum. Research topics discussed specifically
included (1) epilepsy in the developing brain; (2) novel targets for innovative
diagnostics and treatment of epilepsy; (3) what is required for prevention and
cure of epilepsy; and (4) epilepsy and comorbidities, with a special focus on
aging and mental health. This report provides a summary of recommendations that
emerged at ERF2013 about how to (1) strengthen epilepsy research, (2) reduce the
treatment gap, and (3) reduce the burden and stigma associated with epilepsy.
Half of the 6 million European citizens with epilepsy feel stigmatized and
experience social exclusion, stressing the need for funding trans-European
awareness campaigns and monitoring their impact on stigma, in line with the
global commitment of the European Commission and with the recommendations made in
the 2011 Written Declaration on Epilepsy. Epilepsy care has high rates of
misdiagnosis and considerable variability in organization and quality across
European countries, translating into huge societal cost (0.2% GDP) and stressing
the need for cost-effective programs of harmonization and optimization of
epilepsy care throughout Europe. There is currently no cure or prevention for
epilepsy, and 30% of affected persons are not controlled by current treatments,
stressing the need for pursuing research efforts in the field within Horizon
2020. Priorities should include (1) development of innovative biomarkers and
therapeutic targets and strategies, from gene and cell-based therapies to
technologically advanced surgical treatment; (2) addressing issues raised by
pediatric and aging populations, as well as by specific etiologies and
comorbidities such as traumatic brain injury (TBI) and cognitive dysfunction,
toward more personalized medicine and prevention; and (3) translational studies
and clinical trials built upon well-established European consortia.
PMID- 26415923
TI - Perspectives of clinical handover processes: a multi-site survey across different
health professionals.
AB - AIMS AND OBJECTIVES: To examine the perspectives of health professionals of
different disciplines about clinical handover. BACKGROUND: Ineffective handovers
can cause major problems relating to the lack of delivery of appropriate care.
DESIGN: A prospective, cross-sectional design was conducted using a survey about
clinical handover practices. METHODS: Health professionals employed in public
metropolitan hospitals, public rural hospitals and community health centres were
involved. The sample comprised doctors, nurses and allied health professionals,
including physiotherapists, social workers, pharmacists, dieticians and midwives
employed in Western Australia, New South Wales, South Australia and the
Australian Capital Territory. The survey sought information about health
professionals' experiences about clinical handover; their perceived effectiveness
of clinical handover; involvement of patients and family members; health
professionals' ability to confirm understanding and to clarify clinical
information; role modelling behaviour of health professionals; training needs;
adverse events encountered and possibilities for improvements. RESULTS: In all,
707 health professionals participated (response rate = 14%). Represented
professions were nursing (60%), medicine (22%) and allied health (18%). Many
health professionals reported being aware of adverse events where they noticed
poor handover was a significant cause. Differences existed between health
professions in terms of how effectively they gave handover, perceived
effectiveness of bedside handover vs. nonbedside handover, patient and family
involvement in handover, respondents' confirmation of understanding handover from
their perspective, their observation of senior health professionals giving
feedback to junior health professionals, awareness of adverse events and severity
of adverse events relating to poor handovers. CONCLUSIONS: Complex barriers
impeded the conduct of effective handovers, including insufficient opportunities
for training, lack of role modelling, and lack of confidence and understanding
about handover processes. RELEVANCE TO CLINICAL PRACTICE: Greater focus should be
placed on creating opportunities for senior health professionals to act as role
models. Sophisticated approaches should be implemented in training and education.
PMID- 26415922
TI - [Retroperitoneal fibrosis in adults: Main characteristics and relevance of the
diagnostic procedures based on a retrospective multicenter study on 77 cases].
AB - INTRODUCTION: Retroperitoneal fibrosis (RPF) is a rare disorder characterized by
the sheathing of retroperitoneal structures by fibro-inflammatory process. It can
be either isolated or associated with an underlying disease or condition. In the
absence of consistent and consensual approach, the objective of this study was to
assess the relevance of diagnostic tests performed during the diagnostic work-up
of RPF. METHODS: Seventy-seven patients were included in this retrospective
multicenter study. The diagnosis of RPF was defined by the presence of a
thickened circumferential homogeneous tissue unsheathing the infrarenal aorta,
excluding peri-aneurysmal fibrosis and a clear evidence of a cancer. RESULTS: In
62 cases (80.5%), the RPF was considered as being primary or "idiopathic".
Surgical (n=31) or CT-guided (n=9) biopsies of the RPF were performed in half of
the patients showing some fibrotic or non-specific inflammatory lesions in 98% of
cases. A bone marrow biopsy was performed in 23 patients leading to diagnosis of
low grade B cell non-Hodgkin lymphoma in a single patient who also had a
monoclonal gammopathy IgM. The systematic search for autoantibodies or serum
tumor markers was of no diagnostic value. CONCLUSIONS: Although the diagnostic
procedure was heterogeneous, no cause or associated disease was found in the
majority of cases of FRP in this series. In the absence of any clinical or
paraclinical evidence suggesting an underlying disease or any atypical features
at presentation, a number of non-invasive tests (autoantibodies, tumor markers,
bone scintigraphy) and also more invasive diagnostic tests (bone marrow and RPF
biopsies) seem of little relevance.
PMID- 26415924
TI - Bayesian modeling and inference for diagnostic accuracy and probability of
disease based on multiple diagnostic biomarkers with and without a perfect
reference standard.
AB - The area under the receiver operating characteristic (ROC) curve (AUC) is used as
a performance metric for quantitative tests. Although multiple biomarkers may be
available for diagnostic or screening purposes, diagnostic accuracy is often
assessed individually rather than in combination. In this paper, we consider the
interesting problem of combining multiple biomarkers for use in a single
diagnostic criterion with the goal of improving the diagnostic accuracy above
that of an individual biomarker. The diagnostic criterion created from multiple
biomarkers is based on the predictive probability of disease, conditional on
given multiple biomarker outcomes. If the computed predictive probability exceeds
a specified cutoff, the corresponding subject is allocated as 'diseased'. This
defines a standard diagnostic criterion that has its own ROC curve, namely, the
combined ROC (cROC). The AUC metric for cROC, namely, the combined AUC (cAUC), is
used to compare the predictive criterion based on multiple biomarkers to one
based on fewer biomarkers. A multivariate random-effects model is proposed for
modeling multiple normally distributed dependent scores. Bayesian methods for
estimating ROC curves and corresponding (marginal) AUCs are developed when a
perfect reference standard is not available. In addition, cAUCs are computed to
compare the accuracy of different combinations of biomarkers for diagnosis. The
methods are evaluated using simulations and are applied to data for Johne's
disease (paratuberculosis) in cattle.
PMID- 26415925
TI - Cytotoxic effects of 4-octylphenol on fish hepatocytes.
AB - The present study was conducted to determine cytotoxic effects of 4-octylphenol
(4-OP) on primary cultured hepatocytes of pearl mullet (Alburnus tarichi).
Lactate dehydrogenase (LDH) release, malondialdehyde (MDA) level, antioxidant
enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S
transferase (GST)] and glutathione (GSH) content were measured after 24-h
exposure to 4-OP. 4-OP caused dose- and time-dependent increases in LDH release.
Significant induction of MDA level and decrease in GSH content were found. SOD
and GPx activities were decreased while GST activity was increased. These
findings suggest that 4-OP leads to cytotoxicity by depressing antioxidant
defenses in fish hepatocytes.
PMID- 26415926
TI - Evaluation of rational use of veterinary drugs especially antimicrobials and
anthelmintics in Bishoftu, Central Ethiopia.
AB - BACKGROUND: Rational use of drugs in veterinary medicine has numerous benefits,
such as increasing efficacy, decreasing the potential adverse effects, reducing
risk of drug residue and combating development of microorganism's drug
resistance. METHODS: A retrospective study with the aim of evaluating the current
rational use of veterinary drugs was conducted at college of veterinary medicine
and agriculture veterinary teaching hospital and Ada district veterinary clinic,
central Ethiopia. One thousand eight hundred and nineteen animal patients'
encounters were randomly selected for the study from prescription papers and
prescription registration books retrospectively. RESULTS: The average number of
drugs prescribed per encounter was 1.23 with maximum of five. The percentage of
encounters in which antimicrobials and anthelmintics was prescribed were 54.4%
(1216/2235) and 38.9% (869/2235), respectively. The percentages of drugs
prescribed by generic name and from essential veterinary drug list were 90.1%
(2014/2235) and 99.7% (2229/2235), respectively. The most commonly prescribed
antimicrobials and anthelmintics were oxytetracycline 1016 (45.5%), penicillin
and streptomycin combination 168 (7.5%), sulfa drugs 23 (1.0%), and albendazole
732 (32.8%) and ivermectin 137 (6.1%). Among the 1819 animal-patient encounters,
only 57% (n = 1037) of the prescriptions were written adequately, 43% (n = 782)
incorrectly prescribed and 1179 cases of the adequately specified prescription
were tentatively diagnosed. For 656 (53.9%) and 233 (26.8%) inadequately
specified cases antimicrobials and anthelmintics were prescribed, respectively.
Antibiotics were prescribed irrationally for cases which were tentatively
diagnosed as parasitic 21.6 % (n = 262) and viral to prevent secondary bacterial
complications 6.0% (n = 73). Among all patients that were admitted to veterinary
clinics, 96.6% (1757) were treated empirically without getting correct laboratory
supported diagnosis. Chi Square test for trend analysis showed a statistically
significant association between irrational drug usage and year (p = 0.000).
CONCLUSIONS: The findings had shown problems in generic prescribing, incorrect
diagnosis, and non-availability of standard veterinary treatment guideline and
drug formulary in the study area. Therefore, veterinary drugs, specially,
antimicrobial agents should be judiciously used; and a wide scale study to
safeguard the public from drug residual effects and antimicrobial resistance
development is recommended.
PMID- 26415927
TI - RDTs as a source of DNA to study Plasmodium falciparum drug resistance in
isolates from Senegal and the Comoros Islands.
AB - BACKGROUND: The World Health Organization has recommended rapid diagnostic tests
(RDTs) for use in the diagnosis of suspected malaria cases. In addition to
providing quick and accurate detection of Plasmodium parasite proteins in the
blood, these tests can be used as sources of DNA for further genetic studies. As
sulfadoxine-pyrimethamine is used currently for intermittent presumptive
treatment of pregnant women in both Senegal and in the Comoros Islands,
resistance mutations in the dhfr and dhps genes were investigated using DNA
extracted from RDTs. METHODS: The proximal portion of the nitrocellulose membrane
of discarded RDTs was used for DNA extraction. This genomic DNA was amplified
using HRM to genotype the molecular markers involved in resistance to sulfadoxine
pyrimethamine: dhfr (51, 59, 108, and 164) and dhps (436, 437, 540, 581, and
613). Additionally, the msp1 and msp2 genes were amplified to determine the
average clonality between Grande-Comore (Comoros) and Thies (Senegal). RESULTS: A
total of 201 samples were successfully genotyped at all codons by HRM; whereas,
in 200 msp1 and msp2 genes were successfully amplified and genotyped by nested
PCR. A high prevalence of resistance mutations were observed in the dhfr gene at
codons 51, 59, and 108 as well as in the dhps gene at codons 437 and 436. A novel
mutant in dhps at codon positions 436Y/437A was observed. The dhfr I164L codon
and dhps K540 and dhps A581G codons had 100 % wild type alleles in all samples.
CONCLUSION: The utility of field-collected RDTs was validated as a source of DNA
for genetic studies interrogating frequencies of drug resistance mutations, using
two different molecular methods (PCR and High Resolution Melting). RDTs should
not be discarded after use as they can be a valuable source of DNA for genetic
and epidemiological studies in sites where filter paper or venous blood collected
samples are nonexistent.
PMID- 26415928
TI - A comparative study of red and blue light-emitting diodes and low-level laser in
regeneration of the transected sciatic nerve after an end to end neurorrhaphy in
rabbits.
AB - This study aimed at evaluating the effects of red and blue light-emitting diodes
(LED) and low-level laser (LLL) on the regeneration of the transected sciatic
nerve after an end-to-end neurorrhaphy in rabbits. Forty healthy mature male New
Zealand rabbits were randomly assigned into four experimental groups: control,
LLL (680 nm), red LED (650 nm), and blue LED (450 nm). All animals underwent the
right sciatic nerve neurotmesis injury under general anesthesia and end-to-end
anastomosis. The phototherapy was initiated on the first postoperative day and
lasted for 14 consecutive days at the same time of the day. On the 30th day post
surgery, the animals whose sciatic nerves were harvested for histopathological
analysis were euthanized. The nerves were analyzed and quantified the following
findings: Schwann cells, large myelinic axons, and neurons. In the LLL group, as
compared to other groups, an increase in the number of all analyzed aspects was
observed with significance level (P < 0.05). This finding suggests that
postoperative LLL irradiation was able to accelerate and potentialize the
peripheral nerve regeneration process in rabbits within 14 days of irradiation.
PMID- 26415929
TI - Effects of low-level laser therapy on the expression of osteogenic genes during
the initial stages of bone healing in rats: a microarray analysis.
AB - This study evaluated the morphological changes produced by LLLT on the initial
stages of bone healing and also studied the pathways that stimulate the
expression of genes related to bone cell proliferation and differentiation. One
hundred Wistar rats were divided into control and treated groups. Noncritical
size bone defects were surgically created at the upper third of the tibia. Laser
irradiation (Ga-Al-As laser 830 nm, 30 mW, 94 s, 2.8 J) was performed for 1, 2,
3, 5, and 7 sessions. Histopathology revealed that treated animals produced
increased amount of newly formed bone at the site of the injury. Moreover,
microarray analysis evidenced that LLLT produced a significant increase in the
expression TGF-beta, BMP, FGF, and RUNX-2 that could stimulate osteoblast
proliferation and differentiation, which may be related to improving the
deposition of newly formed bone at the site of the injury. Thus, it is possible
to conclude that LLLT improves bone healing by producing a significant increase
in the expression of osteogenic genes.
PMID- 26415930
TI - The case for using country-specific scoring coefficients for scoring the SF-12,
with scoring implications for the SF-36.
AB - PURPOSE: To examine the validity of using the same scoring coefficients across
countries for the SF-12. METHODS: We test the equality of scoring coefficients
derived for a contraction of the SF-36, the Short Form 12 (SF-12), using a large
international database drawn from nine countries, to test equality between
Australia and twelve other country/language groups. First, we checked that the
theoretical structure of the SF-12 as set out by Ware and colleagues, but
including a correlation between physical and mental health, provided an adequate
fit to the data for each country/language group in a confirmatory factor
analysis. We then compared Australia to all of these country/language groups in
multiple-group models to assess whether a model producing common factor score
coefficients provided an adequate fit to the data. We also derived Chi-squared
tests for the differences between the restricted and unrestricted models, to test
the equality of the factor score coefficients across countries. RESULTS: We found
that the theoretical structure of the SF-12, with a correlation between physical
and mental health, provides an adequate fit to the data for all country/language
groups except Hungary. Further, all the unrestricted multiple-group models
provide an adequate fit to the data. In contrast, none of the multiple-group
models restricted to common parameters provide an adequate fit to the data. The
significance tests confirm that the constraints on parameter values produce
significantly different models to the unrestricted models. CONCLUSIONS: We
conclude that researchers should derive their own country-specific scoring
coefficients for physical and mental health summary scores.
PMID- 26415931
TI - Differences between work and leisure in temporal patterns of objectively measured
physical activity among blue-collar workers.
AB - BACKGROUND: Leisure time physical activity (LTPA) is generally associated with
favorable cardiovascular health outcomes, while occupational physical activity
(OPA) shows less clear, or even opposite, cardiovascular effects. This apparent
paradox is not sufficiently understood, but differences in temporal patterns of
OPA and LTPA have been suggested as one explanation. Our aim was to investigate
the extent to which work and leisure (non-occupational time) differ in temporal
activity patterns among blue-collar workers, and to assess the modification of
these patterns by age and gender. METHODS: This study was conducted on a cross
sectional sample of male (n = 108) and female (n = 83) blue-collar workers, aged
between 21 and 65 years. Physical activity and sedentary behavior were assessed
using accelerometers (Actigraph GT3X+) worn on the thigh and trunk for four
consecutive days. Temporal patterns of OPA and LTPA were retrieved using Exposure
Variation Analysis (EVA), and expressed in terms of percentage of work and
leisure time spent in uninterrupted periods of different durations (<1 min, 1-5
min, 5-10 min, 10-30 min, 30-60 min and > 60 min) of sitting, standing, and
walking. Repeated measures ANOVA and linear regression analyses were used to test
a) possible differences between OPA and LTPA in selected EVA derivatives, and b)
the modification of these differences by age and gender. RESULTS: OPA showed a
larger percentage time walking in brief (<5 min) periods [mean (SD): 33.4 %
(12.2)], and less time in prolonged (>30 min) sitting [7.0 % (9.3)] than LTPA
[walking 15.4 % (5.0); sitting 31.9 % (15.3)], even after adjustment for the
difference between work and leisure in total time spent in each activity type.
These marked differences in the temporal pattern of OPA and LTPA were modified by
gender, but not age. CONCLUSION: We found that the temporal patterns of OPA and
LTPA among blue-collar workers were markedly different even after adjustment for
total physical activity time, and that this difference was modified by gender. We
recommend using EVA derivatives in future studies striving to disentangle the
apparent paradoxical cardiovascular effect of physical activity at work and
during leisure.
PMID- 26415933
TI - Injuries of neural tracts in a patient with CADASIL: a diffusion tensor imaging
study.
AB - BACKGROUND: We report a patient with cerebral autosomal dominant arteriopathy
with subcortical infarcts and leukoencephalopathy (CADASIL), who showed injuries
of the neural tracts, which was demonstrated by diffusion tensor tractography
(DTT). CASE PRESENTATION: A 64-year-old male patient and seven age-matched
control volunteers were recruited. Since approximately 1.5 years ago, he had felt
mild weakness of the right arm and was diagnosed as CADASIL by the finding of the
exon 11 mutation of the NOTCH3 gene approximately 10 months ago. T2-weighted and
FLAIR brain MRI images obtained at admission showed high signal intensity lesions
in the subcortical gray matter and periventricular white matter. He showed mild
quadriparesis, mild dysarthria, mild cognitive impairment, and emotional
problems. Diffusion tensor imaging was performed and nine neural tracts
(corticospinal tract, corticobulbar tract, corticofugal tract from the
supplementary motor area, corticofugal tract from the premotor cortex,
thalmoprefrontal tract [TPT] to the dorsolateral prefrontal cortex, TPT to the
ventrolateral prefrontal cortex, TPT to the orbitoprefrontal cortex, fornix, and
cingulum) were reconstructed. Fractional anisotropy (FA), mean diffusivity (MD),
and tract volume of each neural tract were measured. All neural tracts except for
the left fornix showed at least one more abnormality in terms of DTT parameters
(decrement of FA, increment of MD, or decrement of tract volume). CONCLUSION: We
demonstrated injuries of the neural tracts in a patient with CADASIL. It appears
that clinical manifestations in this patient were related to injuries of the
neural tracts.
PMID- 26415932
TI - A survey of perceived training differences between ophthalmology residents in
Hong Kong and China.
AB - BACKGROUND: To study the differences in ophthalmology resident training between
China and the Hong Kong Special Administrative Region (HKSAR). METHODS: Training
programs were selected from among the largest and best-known teaching hospitals.
Ophthalmology residents were sent an anonymous 48-item questionnaire by mail.
Work satisfaction, time allocation between training activities and volume of
surgery performed were determined. RESULTS: 50/75 residents (66.7 %) from China
and 20/26 (76.9 %) from HKSAR completed the survey. Age (28.9 +/- 2.5 vs. 30.2 +/
2.9 years, p = 0.15) and number of years in training (3.4 +/- 1.6 vs. 2.8 +/-
1.5, p = 0.19) were comparable between groups. The number of cataract procedures
performed by HKSAR trainees (extra-capsular, median 80.0, quartile range: 30.0,
100.0; phacoemulsification, median: 20.0, quartile range: 0.0, 100.0) exceeded
that for Chinese residents (extra-capsular: median = 0, p < 0.0001;
phacoemulsification: median = 0, p < 0.0001). Chinese trainees spent more time
completing medical charts (>50 % of time on charts: 62.5 % versus 5.3 %, p <
0.0001) and received less supervision (>=90 % of training supervised: 4.4 %
versus 65 %, p < 0.0001). Chinese residents were more likely to feel underpaid
(96.0 % vs. 31.6 %, p < 0.0001) and hoped their children would not practice
medicine (69.4 % vs. 5.0 %, p = 0.0001) compared HKSAR residents. CONCLUSIONS: In
this study, ophthalmology residents in China report strikingly less surgical
experience and supervision, and lower satisfaction than HKSAR residents. The
HKSAR model of hands-on resident training might be useful in improving the low
cataract surgical rate in China.
PMID- 26415934
TI - QCT of the proximal femur--which parameters should be measured to discriminate
hip fracture?
AB - SUMMARY: For quantitative computed tomography (QCT), most relevant variables to
discriminate hip fractures were determined. A multivariate analysis showed that
trabecular bone mineral density (BMD) of the trochanter with "cortical" thickness
of the neck provided better fracture discrimination than total hip integral BMD.
A slice-by-slice analysis of the neck or the inclusion of strength-based
parameters did not improve fracture discrimination. INTRODUCTION: For QCT of the
proximal femur, a large variety of analysis parameters describing bone mineral
density, geometry, or strength has been considered. However, in each given study,
generally just a small subset was used. The aim of this study was to start with a
comprehensive set and then select a best subset of QCT parameters for
discrimination of subjects with and without acute osteoporotic hip fractures.
METHODS: The analysis was performed using the population of the European Femur
Fracture (EFFECT) study (Bousson et al. J Bone Min Res: Off J Am Soc Bone Min Res
26:881-893, 2011). Fifty-six female control subjects (age 73.2 +/- 9.3 years)
were compared with 46 female patients (age 80.9 +/- 11.1 years) with acute hip
fractures. The QCT analysis software MIAF-Femur was used to virtually dissect the
proximal femur and analyze more than 1000 parameters, predominantly in the
femoral neck. A multivariate best-subset analysis was used to extract the
parameters best discriminating hip fractures. All results were adjusted for age,
height, and weight differences between the two groups. RESULTS: For the
discrimination of all proximal hip fractures as well as for cervical fractures
alone, the measurement of neck parameters suffices (area under the curve (AUC) =
0.84). Parameters characterizing bone strength are discriminators of hip
fractures; however, in multivariate models, only "cortical" cross-sectional area
in the neck center remained as a significant contributor. The combination of one
BMD parameter, trabecular BMD of the trochanter, and one geometry parameter,
"cortical" thickness of the neck discriminated hip fracture with an AUC value of
0.83 which was significantly better than 0.77 for total femur BMD alone. A
comprehensive slice-based analysis of the neck along its axis did not
significantly improve hip fracture discrimination. CONCLUSIONS: If QCT of the hip
is performed, the analysis should include neck and trochanter. In particular, for
fractures of any type, a comprehensive slice-based analysis of the neck along its
axis did not significantly improve hip fracture discrimination nor did the
inclusion of strength-related parameters other than "cortical" area or thickness.
One BMD and one geometry parameter, in this study, the combination of trabecular
BMD of the trochanter and of "cortical" thickness of the neck resulted in
significant hip fracture discrimination.
PMID- 26415935
TI - A flow cytometric approach to study the mechanism of gene delivery to cells by
gemini-lipid nanoparticles: an implication for cell membrane nanoporation.
AB - BACKGROUND: Gemini-lipid nanoparticles have been received major attention
recently as non-viral delivery systems due to their successful non-invasive gene
delivery through tough barriers such as eye and skin. The aim of this study was
to evaluate non-viral gene delivery by a series of dicationic gemini surfactant
phospholipid nanoparticles (GL-NPs) and to explore their mechanism of interaction
with cellular membranes of murine PAM212 epidermal keratinocytes. METHODS: NPs
containing pCMV-tdTomato plasmid encoding red fluorescent protein (RFP) were
prepared using 12 different gemini surfactants (m-s-m, with m = 12, 16 and 18C
alkyl tail and s = 3 and 7C polymethylene spacer group and 7C substituted spacers
with 7NH and 7NCH3) and dioleoylphosphatidylethanolamine helper lipid. RFP gene
expression and cell viability status were evaluated using flow cytometry.
MitoTracker Deep Red mitochondrial stain and the cell impermeable Sytox red
nuclear stain were used as indicators of cell viability and cell membrane
integrity, respectively. RESULTS: No significant viability loss was detected in
cells transfected with 18-3-18, 18-7-18, 18-7NH-18, and 18-7NCH3-18 NPs, whereas
a significant reduction of viability was detected in cells treated with 12-3-12,
12-7-12, 12-7NH-12, 16-7NH-16, or 16-7NCH3-16 GL-NPs. Compared to Lipofectamine
Plus, 18-3-18 GL-NPs showed higher transfection efficiency and comparable
viability profile by evaluation using MitoTracker Deep Red in PAM212 cells. Flow
cytometric analysis of PAM212 cells stained with Sytox red revealed two cell
populations with low and high fluorescent intensity, representing cells with
partially-porated and highly-porated membranes, respectively. Additional combined
staining with MitoTracker and ethidium homodimer showed that that 18-3-18 GL-NPs
disturbed cell membrane integrity, while cells were still alive and had
mitochondrial activity. CONCLUSION: Taken together, this study demonstrated that
18-3-18 GL-NPs have higher transfection efficiency and comparable viability
profile to the commercial Lipofectamine Plus, and the interaction of 18-3-18 GL
NPs with PAM212 cell membranes involves a permeability increase, possibly through
the formation of nanoscale pores, which could explain efficient gene delivery.
This novel nanoconstruct appears to be a promising delivery system for further
skin gene therapy studies in vivo.
PMID- 26415937
TI - MRI scanning increases eightfold in Canadian women with breast cancer.
PMID- 26415938
TI - Editorial: Cell therapy and regenerative medicine.
PMID- 26415936
TI - Adenosine A2A receptor plays an important role in radiation-induced dermal
injury.
AB - Ionizing radiation is a common therapeutic modality and following irradiation
dermal changes, including fibrosis and atrophy, may lead to permanent changes. We
have previously demonstrated that occupancy of A2A receptor (A2AR) stimulates
collagen production, so we determined whether blockade or deletion of A2AR could
prevent radiation-induced fibrosis. After targeted irradiation (40 Gy) of the
skin of wild-type (WT) or A2AR knockout (A2ARKO) mice, the A2AR antagonist
ZM241385 was applied daily for 28 d. In irradiated WT mice treated with the A2AR
antagonist, there was a marked reduction in collagen content and skin thickness,
and ZM241385 treatment reduced the number of myofibroblasts and angiogenesis.
After irradiation, there is an increase in loosely packed collagen fibrils, which
is significantly diminished by ZM241385. Irradiation also induced an increase in
epidermal thickness, prevented by ZM241385, by increasing the number of
proliferating keratinocytes. Similarly, in A2ARKO mice, the changes in collagen
alignment, skin thickness, myofibroblast content, angiogenesis, and epidermal
hyperplasia were markedly reduced following irradiation. Radiation-induced
changes in the dermis and epidermis were accompanied by an infiltrate of T cells,
which was prevented in both ZM241385-treated and A2ARKO mice. Radiation therapy
is administered to a significant number of patients with cancer, and radiation
reactions may limit this therapeutic modality. Our findings suggest that topical
application of an A2AR antagonist prevents radiation dermatitis and may be useful
in the prevention or amelioration of radiation changes in the skin.
PMID- 26415939
TI - Prevalence and clinical correlates of Schistosoma mansoni co-infection among
malaria infected patients, Northwest Ethiopia.
AB - BACKGROUND: In Ethiopia, where malaria and schistosomiasis are co-endemic, co
infections are expected to be high. However, data about the prevalence of malaria
schistosomiasis co-infection and their clinical correlation is lacking.
Therefore, the aim of this study was to assess prevalence of Schistosoma mansoni
co-infection and associated clinical correlates in malaria patients. METHODS: A
cross-sectional study was conducted in 2013 at Chwahit Health Center, in
northwest Ethiopia. Blood film positive malaria patients (N = 205) were recruited
for the study. Clinical, parasitological, hematological, and biochemical
parameters were assessed from every study participant. Stool samples were also
collected and processed with Kato-Katz technique to diagnose and classify
intensity of Schistosoma mansoni. RESULTS: The prevalence of Schistosoma mansoni
and malaria co-infection was 19.5%. The age group of 16-20 years old was
significantly associated with co-infection. Co-infected patients with a moderate
heavy egg burden of Schistosoma mansoni had significantly high mean Plasmodium
parasitemia. On the other hand, age group of 6-10 years old and moderate-heavy
Schistosoma mansoni co-infection were significantly associated with severe
malaria. CONCLUSIONS: Prevalence of malaria and Schistosoma mansoni co-infection
in the study area was considerably high. Severity of malaria and parasitemia of
Plasmodium were associated with certain age groups and intensity of concurrent
Schistosoma mansoni. Further study is needed to explore the underlying mechanisms
of interaction between malaria and Schistosoma mansoni.
PMID- 26415940
TI - Survival of the grouped, or three's a crowd? Repetition blindness in groups of
letters and words.
AB - When stimuli are presented rapidly, repetitions are often undetected--a
phenomenon called "repetition blindness" (RB; Kanwisher Cognition, 27, 117-143,
1987). Grouping of nonlinguistic items has been found to prevent RB (Goldfarb &
Treisman Psychonomic Bulletin & Review, 18, 1042-1049, 2011). In order to
determine whether this effect could be found with letters and words, participants
viewed rapid serial visual presentation and brief simultaneous visual
presentation streams containing groups of linguistic stimuli and provided
judgments of frequency. The collection of reaction times and an explicit question
about strategy use allowed for analyses of the participants' processing
strategies. Two groups of participants emerged: one that demonstrated RB for
groups of stimuli, and another that demonstrated enhanced perception with
stimulus grouping. These participant groups did not appear to differ on the basis
of explicit processing strategies or reaction times.
PMID- 26415941
TI - Teaching history taking to medical students: a systematic review.
AB - BACKGROUND: This paper is an up-to-date systematic review on educational
interventions addressing history taking. The authors noted that despite the
plethora of specialized training programs designed to enhance students'
interviewing skills there had not been a review of the literature to assess the
quality of each published method of teaching history taking in undergraduate
medical education based on the evidence of the program's efficacy. METHODS: The
databases PubMed, PsycINFO, Google Scholar, opengrey, opendoar and SSRN were
searched using key words related to medical education and history taking.
Articles that described an educational intervention to improve medical students'
history-taking skills were selected and reviewed. Included studies had to
evaluate learning progress. Study quality was assessed using the Medical
Education Research Study Quality Instrument (MERSQI). RESULTS: Seventy-eight full
text articles were identified and reviewed; of these, 23 studies met the final
inclusion criteria. Three studies applied an instructional approach using
scripts, lectures, demonstrations and an online course. Seventeen studies applied
a more experiential approach by implementing small group workshops including role
play, interviews with patients and feedback. Three studies applied a creative
approach. Two of these studies made use of improvisational theatre and one
introduced a simulation using Lego(r) building blocks. Twenty-two studies
reported an improvement in students' history taking skills. Mean MERSQI score was
10.4 (range 6.5 to 14; SD = 2.65). CONCLUSIONS: These findings suggest that
several different educational interventions are effective in teaching history
taking skills to medical students. Small group workshops including role-play and
interviews with real patients, followed by feedback and discussion, are
widespread and best investigated. Feedback using videotape review was also
reported as particularly instructive. Students in the early preclinical state
might profit from approaches helping them to focus on interview skills and not
being distracted by thinking about differential diagnoses or clinical management.
The heterogeneity of outcome data and the varied ways of assessment strongly
suggest the need for further research as many studies did not meet basic
methodological criteria. Randomized controlled trials using external assessment
methods, standardized measurement tools and reporting long-term data are
recommended to evaluate the efficacy of courses on history taking.
PMID- 26415942
TI - Evidence for temporal population replacement and the signature of ecological
adaptation in a major Neotropical malaria vector in Amazonian Peru.
AB - BACKGROUND: The major Neotropical malaria vector, Anopheles darlingi, was
reintroduced into the Iquitos, Loreto, Peru area during the early 1990s, where it
displaced other anophelines and caused a major malaria epidemic. Since then, case
numbers in Loreto have fluctuated, but annual increases have been reported since
2012. METHODS: The population genetic structure of An. darlingi sampled before
and after the introduction of long-lasting insecticidal nets (LLINs) was
investigated to test the hypothesis of temporal population change (2006 vs.
2012). Current samples of An. darlingi were used to test the hypothesis of
ecological adaptation to human modified (highway) compared with wild (riverine)
habitat, linked to forest cover. In total, 693 An. darlingi from nine localities
in Loreto, Peru area were genotyped using 13 microsatellite loci. To test the
hypothesis of habitat differentiation in An. darlingi biting time patterns, HBR
and EIR, four collections of An. darlingi from five localities (two riverine and
three highway) were analysed. RESULTS: Analyses of microsatellite loci from seven
(2006) and nine settlements (2012-2014) in the Iquitos area detected two
distinctive populations with little overlap, although it is unclear whether this
population replacement event is associated with LLIN distribution or climate.
Within the 2012-2014 population two admixed subpopulations, A and B, were
differentiated by habitat, with B significantly overrepresented in highway, and
both in near-equal proportions in riverine. Both subpopulations had a signature
of expansion and there was moderate genetic differentiation between them. Habitat
and forest cover level had significant effects on HBR, such that Plasmodium
transmission risk, as measured by EIR, in peridomestic riverine settlements was
threefold higher than in peridomestic highway settlements. HBR was directly
associated with available host biomass rather than forest cover. CONCLUSIONS: A
population replacement event occurred between 2006 and 2012-2014, concurrently
with LLIN distribution and a moderate El Nino event, and prior to an increase in
malaria incidence. The likely drivers of this replacement cannot be determined
with current data. The present-day An. darlingi population is composed of two
highly admixed subpopulations, which appear to be in an early stage of
differentiation, triggered by anthropogenic alterations to local habitat.
PMID- 26415943
TI - The minimally invasive approach is associated with reduced surgical site
infections in obese patients undergoing proctectomy.
AB - BACKGROUND: While laparoscopic colorectal resection may be underused in
technically challenging circumstances, the minimally invasive approach may in
fact maximally benefit patients at the greatest risk of complications. Obesity
and proctectomy pose particular technical challenges during laparoscopic
resection and are also associated with the greatest risks of complications,
especially surgical site infections (SSIs). We evaluated the role of laparoscopy
in minimizing SSI in such patients. METHODS: From the American College of
Surgeons-National Surgical Quality Improvement Program database, outcomes for
obese [body mass index (BMI) >= 30 kg/m(2)] and non-obese (BMI < 30 kg/m(2))
patients undergoing colectomy or proctectomy between 2006 and 2011 by the
laparoscopic (laparoscopic colectomy, laparoscopic proctectomy) or open (open
colectomy, open proctectomy) approaches were compared. A univariate analysis was
used to determine the influence of laparoscopic surgery within each group on SSI,
and a multivariate analysis evaluated the influence of laparoscopy on SSI for
obese patients undergoing proctectomy. RESULTS: OC patients were more likely than
OP, LC, and LP, respectively, to undergo emergency operation and have an American
Society of Anesthesiologists (ASA) score of 3-5. Overall SSI rates after OC, OP,
LC, and LP were 15.2, 17.6, 8.6, and 10.1 %, respectively (p < 0.001), and for
obese patients, the rates were 18.7, 22.3, 10.7, and 13.3 % (p < 0.001). On
univariate analysis, open surgery, obesity, proctectomy, younger age, race,
steroid use, diabetes, chronic obstructive pulmonary disease, prior wound
infection, transfusion history, previous operation within 30 days, coronary
artery or vascular disease, ASA class 3-5, tobacco use, resident involvement,
male gender, albumin <3.5 g/dL, and emergent operation were associated with a
higher risk of SSI. Laparoscopy reduced the risk of SSI by at least 35 % across
all BMI classes and procedures, an effect that persisted on multivariate analysis
even in obese patients undergoing proctectomy. CONCLUSIONS: In colorectal
surgery, an already high-risk outlier for SSI, obesity and proctectomy are
associated with the highest risk of SSI. Despite the particular technical
challenges of laparoscopy in these circumstances, the minimally invasive approach
attenuates the risk of SSI in these high-risk patients and thus should be
strongly considered during treatment planning.
PMID- 26415944
TI - Strategy for the difficult-to-reach ileal pouch-anal anastomosis: technical steps
of an in vivo application of a mesenteric-lengthening technique.
PMID- 26415945
TI - The negative impact of spasticity on the health-related quality of life of stroke
survivors: a longitudinal cohort study.
AB - BACKGROUND: Spasticity often leads to symptomatic and functional problems that
can cause disability for stroke survivors. We studied whether spasticity has a
negative impact on health-related quality of life (HRQoL). METHODS: As part of
the Greater Cincinnati/Northern Kentucky Stroke Study (NCT00642213), 460 ischemic
stroke patients were interviewed during hospitalization and then followed over
time. HRQoL was measured by the Physical Component Summary (PCS) and Mental
Component Summary (MCS) scores of the Short Form-12 (SF-12), EuroQol-5 dimension
(EQ-5D), and Stroke-Specific Quality of Life (SSQOL) instruments, with lower
scores indicating worse health. HRQoL differences between stroke survivors with
and without spasticity were compared, adjusting for age, race, stroke severity,
pre-stroke function, and comorbidities. RESULTS: Of the 460 ischemic stroke
patients, 328 had spasticity data available 3 months after their stroke (mean age
of 66 years, 49% were female, and 26% were black). Of these patients, 54 (16%)
reported having spasticity. Three months following their stroke, patients who
reported spasticity had lower mean scores on the PCS (29.6 +/- 1.4 vs 37.3 +/-
0.6; P < .001), EQ-5D (0.59 +/- 0.03 vs 0.71 +/- 0.01; P < .001), and SSQOL (3.57
+/- 0.08 versus 3.78 +/- 0.03; P = .03) compared with patients who did not report
spasticity. Lower HRQoL scores were also observed at the 1-year (PCS, EQ-5D, and
SSQOL) and 2-year (EQ-5D and SSQOL) interviews in those with spasticity compared
with those without spasticity. CONCLUSIONS: Statistically and clinically
meaningful differences in HRQoL exist between stroke survivors with and without
spasticity.
PMID- 26415946
TI - Implementation of safety checklists in surgery: a realist synthesis of evidence.
AB - AIM: The aim of this review is to present a realist synthesis of the evidence of
implementation interventions to improve adherence to the use of safety checklists
in surgery. BACKGROUND: Surgical safety checklists have been shown to improve
teamwork and patient safety in the operating room. Yet, despite the benefits
associated with their use, universal implementation of and compliance with these
checklists has been inconsistent. DATA SOURCES: An overview of the literature
from 2008 is examined in relation to checklist implementation, compliance, and
sustainability. REVIEW METHODS: Pawson's and Rycroft-Malone's realist synthesis
methodology was used to explain the interaction between context, mechanism, and
outcome. This approach incorporated the following: defining the scope of the
review, searching and appraising the evidence, extracting and synthesising the
findings, and disseminating, implementing, and evaluating the evidence. We
identified two theories a priori that explained contextual nuances associated
with implementation and evaluation of checklists in surgery: the Normalisation
Process Theory and Responsive Regulation Theory. RESULTS: We identified four a
priori propositions: (1) Checklist protocols that are prospectively tailored to
the context are more likely to be used and sustained in practice, (2) Fidelity
and sustainability is increased when checklist protocols can be seamlessly
integrated into daily professional practice, (3) Routine embedding of checklist
protocols in practice is influenced by factors that promote or inhibit
clinicians' participation, and (4) Regulation reinforcement mechanisms that are
more contextually responsive should lead to greater compliance in using checklist
protocols. The final explanatory model suggests that the sustained use of
surgical checklists is discipline-specific and is more likely to occur when
medical staff are actively engaged and leading the process of implementation.
Involving clinicians in tailoring the checklist to better fit their context of
practice and giving them the opportunity to reflect and evaluate the
implementation intervention enables greater participation and ownership of the
process. CONCLUSIONS: A major limitation in the surgical checklist literature is
the lack of robust descriptions of intervention methods and implementation
strategies. Despite this, two consequential findings have emerged through this
realist synthesis: First, the sustained use of surgical checklists is discipline
specific and is more successful when physicians are actively engaged and leading
implementation. Second, involving clinicians in tailoring the checklist to their
context and encouraging them to reflect on and evaluate the implementation
process enables greater participation and ownership.
PMID- 26415948
TI - Erratum to: Early postoperative mortality after simultaneous or staged bilateral
primary total hip arthroplasty: an observational register study from the Swedish
Hip Arthroplasty Register.
PMID- 26415947
TI - The PfAlba1 RNA-binding protein is an important regulator of translational timing
in Plasmodium falciparum blood stages.
AB - BACKGROUND: Transcriptome-wide ribosome occupancy studies have suggested that
during the intra-erythrocytic lifecycle of Plasmodium falciparum, select mRNAs
are post-transcriptionally regulated. A subset of these encodes parasite
virulence factors required for invading host erythrocytes, and are currently
being developed as vaccine candidates. However, the molecular mechanisms that
govern post-transcriptional regulation are currently unknown. RESULTS: We explore
the previously identified DNA/RNA-binding protein PfAlba1, which localizes to
multiple foci in the cytoplasm of P. falciparum trophozoites. We establish that
PfAlba1 is essential for asexual proliferation, and subsequently investigate
parasites overexpressing epitope-tagged PfAlba1 to identify its RNA targets and
effects on mRNA homeostasis and translational regulation. Using deep sequencing
of affinity-purified PfAlba1-associated RNAs, we identify 1193 transcripts that
directly bind to PfAlba1 in trophozoites. For 105 such transcripts, 43 % of which
are uncharacterized and 13 % of which encode erythrocyte invasion components, the
steady state levels significantly change at this stage, evidencing a role for
PfAlba1 in maintaining mRNA homeostasis. Additionally, we discover that binding
of PfAlba1 to four erythrocyte invasion mRNAs, Rap1, RhopH3, CDPK1, and AMA1, is
linked to translation repression in trophozoites whereas release of these mRNAs
from a PfAlba1 complex in mature stages correlates with protein synthesis.
CONCLUSIONS: We show that PfAlba1 binds to a sub-population of asexual stage
mRNAs and fine-tunes the timing of translation. This mode of post-transcriptional
regulation may be especially important for P. falciparum erythrocyte invasion
components that have to be assembled into apical secretory organelles in a highly
time-dependent manner towards the end of the parasite's asexual lifecycle.
PMID- 26415949
TI - Effects of Vascular Endothelial Growth Factor in Recovery Phase of Acute Lung
Injury in Mice.
AB - AIM: To test the hypothesis that exogenous administration of vascular endothelial
growth factor (VEGF) promotes lung repair in acute lung injury (ALI). METHODS:
ALI was induced by intranasal lipopolysaccharide (LPS) administration in mice,
followed by different treatment protocols for 7 days in 3 groups (n = 6, each)
including the LPS, the VEGF and the anti-VEGF group. At day 7, peripheral blood
and lungs were collected. Lung wet-to-dry (W/D) ratio and lung injury score were
measured. Immunohistochemistry assay was employed to detect the number of
pulmonary vessels. Circulating endothelial progenitor cells (EPCs) was detected
using flow cytometric analysis, and the apoptosis of lung cells was determined by
TUNEL staining. RESULTS: VEGF treatment reduced W/D ratio and pulmonary
neutrophil infiltration in the VEGF group compared with the LPS group. The
treatment of VEGF increased the number of pulmonary vessels, and significantly
increased the number of circulating EPC cells. Moreover, administration of VEGF
decreased the percentage of apoptotic cells in the VEGF group. CONCLUSIONS: Our
results suggest that VEGF may contribute to vascular endothelial repair and
function as a protective factor against ALI.
PMID- 26415950
TI - Sublethal imidacloprid effects on honey bee flower choices when foraging.
AB - Neonicotinoids, systemic neuro-active pesticides similar to nicotine, are widely
used in agriculture and are being investigated for a role in honey bee colony
losses. We examined one neonicotinoid pesticide, imidacloprid, for its effects on
the foraging behavior of free-flying honey bees (Apis mellifera anatoliaca)
visiting artificial blue and white flowers. Imidacloprid doses, ranging from 1/5
to 1/50 of the reported LD50, were fed to bees orally. The study consisted of
three experimental parts performed sequentially without interruption. In Part 1,
both flower colors contained a 4 MUL 1 M sucrose solution reward. Part 2 offered
bees 4 MUL of 1.5 M sucrose solution in blue flowers and a 4 MUL 0.5 M sucrose
solution reward in white flowers. In Part 3 we reversed the sugar solution
rewards, while keeping the flower color consistent. Each experiment began 30 min
after administration of the pesticide. We recorded the percentage of experimental
bees that returned to forage after treatment. We also recorded the visitation
rate, number of flowers visited, and floral reward choices of the bees that
foraged after treatment. The forager return rate declined linearly with
increasing imidacloprid dose. The number of foraging trips by returning bees was
also affected adversely. However, flower fidelity was not affected by
imidacloprid dose. Foragers visited both blue and white flowers extensively in
Part 1, and showed greater fidelity for the flower color offering the higher
sugar solution reward in Parts 2 and 3. Although larger samples sizes are needed,
our study suggests that imidacloprid may not affect the ability to select the
higher nectar reward when rewards were reversed. We observed acute, mild effects
on foraging by honey bees, so mild that storage of imidacloprid tainted-honey is
very plausible and likely to be found in honey bee colonies.
PMID- 26415951
TI - Label noise in subtype discrimination of class C G protein-coupled receptors: A
systematic approach to the analysis of classification errors.
AB - BACKGROUND: The characterization of proteins in families and subfamilies, at
different levels, entails the definition and use of class labels. When the
adscription of a protein to a family is uncertain, or even wrong, this becomes an
instance of what has come to be known as a label noise problem. Label noise has a
potentially negative effect on any quantitative analysis of proteins that depends
on label information. This study investigates class C of G protein-coupled
receptors, which are cell membrane proteins of relevance both to biology in
general and pharmacology in particular. Their supervised classification into
different known subtypes, based on primary sequence data, is hampered by label
noise. The latter may stem from a combination of expert knowledge limitations and
the lack of a clear correspondence between labels that mostly reflect GPCR
functionality and the different representations of the protein primary sequences.
RESULTS: In this study, we describe a systematic approach, using Support Vector
Machine classifiers, to the analysis of G protein-coupled receptor
misclassifications. As a proof of concept, this approach is used to assist the
discovery of labeling quality problems in a curated, publicly accessible database
of this type of proteins. We also investigate the extent to which physico
chemical transformations of the protein sequences reflect G protein-coupled
receptor subtype labeling. The candidate mislabeled cases detected with this
approach are externally validated with phylogenetic trees and against further
trusted sources such as the National Center for Biotechnology Information,
Universal Protein Resource, European Bioinformatics Institute and Ensembl Genome
Browser information repositories. CONCLUSIONS: In quantitative classification
problems, class labels are often by default assumed to be correct. Label noise,
though, is bound to be a pervasive problem in bioinformatics, where labels may be
obtained indirectly through complex, many-step similarity modelling processes. In
the case of G protein-coupled receptors, methods capable of singling out and
characterizing those sequences with consistent misclassification behaviour are
required to minimize this problem. A systematic, Support Vector Machine-based
method has been proposed in this study for such purpose. The proposed method
enables a filtering approach to the label noise problem and might become a
support tool for database curators in proteomics.
PMID- 26415952
TI - Is accurate and reliable blood loss estimation the 'crucial step' in early
detection of postpartum haemorrhage: an integrative review of the literature.
AB - BACKGROUND: Postpartum haemorrhage (PPH) is the leading cause of maternal
mortality in low-income countries and severe maternal morbidity in many high
income countries. Poor outcomes following PPH are often attributed to delays in
the recognition and treatment of PPH. Experts have suggested that improving the
accuracy and reliability of blood loss estimation is the crucial step in
preventing death and morbidity from PPH. However, there is little guidance on how
this can be achieved. The aim of this integrative review was to evaluate the
various methods of assessing maternal blood loss during childbirth. METHODS: A
systematic, integrative review of published research studies was conducted. All
types of studies were included if they developed, tested, or aimed to improve
methods and skills in quantifying blood loss during childbirth, or explored
experiences of those involved in the process. RESULTS: Thirty-six studies were
included that evaluated the accuracy of visual estimation; tested methods to
improve skills in measurement; examined their effect on PPH diagnosis and
treatment, and / or explored additional factors associated with blood loss
evaluation. The review found that health professionals were highly inaccurate at
estimating blood loss as a volume. Training resulted in short term improvements
in skills but these were not retained and did not improve clinical outcomes.
Multi-faceted interventions changed some clinical practices but did not reduce
the incidence of severe PPH or the timing of responses to excessive bleeding.
Blood collection bags improved the accuracy of estimation but did not prevent
delays or progression to severe PPH. Practitioners commonly used the nature and
speed of blood flow, and the condition of the woman to indicate that the blood
loss was abnormal. CONCLUSIONS: Early diagnosis of PPH should improve maternal
outcomes, but there is little evidence that this can be achieved through
improving the accuracy of blood loss volume measurements. The diagnosis may rely
on factors other than volume, such as speed of blood flow and nature of loss. A
change in direction of future research is required to explore these in more
detail.
PMID- 26415953
TI - Antidepressants normalize elevated Toll-like receptor profile in major depressive
disorder.
AB - RATIONALE: Abnormalities in Toll-like receptor (TLR) expression in depression
have been inferred in part from observed increases in TLR4 levels in peripheral
blood mononuclear cells (PBMCs) and postmortem brains of depressed and suicidal
patients. Our previous study found differences in the TLR expression in PBMCs
between healthy controls and patients with major depressive disorder.
Normalization of increased TLR4 in PBMCs by cognitive behavior psychotherapy has
been reported. However, the effects of antidepressants remain unknown.
OBJECTIVES: Changes in TLR1-9 expression levels of PBMCs were examined in 56
patients with MDD. The 17-item Hamilton Depression Rating Scale (HAMD-17) and
mRNA expression levels of TLRs were assessed in parallel with a housekeeping gene
using qRT-PCR before and after treatment with antidepressants. RESULTS: TLR3,
TLR4, TLR5, TLR7, TLR8, and TLR9 were expressed at elevated levels in patients
with MDD and were significantly decreased by treatment with antidepressants for 4
weeks. Antidepressant treatment completely normalized TLR3, TLR5, TLR7, TLR8, and
TLR9 levels, whereas TLR1, TLR2, TLR4, and TLR6 were decreased to below normal
levels. A subgroup analysis found that only TLR3 was significantly higher at
baseline in the nonremission group. In addition, a multiple linear regression
analysis revealed that only low TLR3 before treatment predicted improvement in
HAMD-17 scores. CONCLUSIONS: These findings suggest that antidepressant treatment
exerts anti-inflammatory effects in patients with MDD and identify TLR profiles
as a predictor of response to antidepressant therapy. Further studies
investigating the effects of manipulating individual TLRs on depression are
needed to fully elucidate the underlying mechanism.
PMID- 26415956
TI - Participant-Direction in a Culturally Diverse, Rural Population: The Hawaii
Community Living Program.
AB - The Hawaii Community Living Program was a participant-direction pilot project
aimed at rural, multicultural, and community-dwelling older adults at risk of
institutionalization. This evaluation examined participant outcomes, and explored
the role of culture, health literacy, and rural settings in participant-direction
programs. The program enrolled 91 participants and, of these enrollees, helped 84
(92.3%) participants avoid institutionalization and spend down to Medicaid.
Findings indicated that Program Coaches needed to be culturally appropriate and
creative in arranging for services and the delivery of goods and supplies.
Results suggested that participants need to be health literate to direct their
care, but further research is needed.
PMID- 26415954
TI - The continuous performance test (rCPT) for mice: a novel operant touchscreen test
of attentional function.
AB - RATIONALE: Continuous performance tests (CPTs) are widely used to assess
attentional processes in a variety of disorders including Alzheimer's disease and
schizophrenia. Common human CPTs require discrimination of sequentially
presented, visually patterned 'target' and 'non-target' stimuli at a single
location. OBJECTIVES: The aims of this study were to evaluate the performance of
three popular mouse strains on a novel rodent touchscreen test (rCPT) designed to
be analogous to common human CPT variants and to investigate the effects of
donepezil, a cholinesterase inhibitor and putative cognitive enhancer. METHODS:
C57BL/6J, DBA/2J and CD1 mice (n = 15-16/strain) were trained to baseline
performance using four rCPT training stages. Then, probe tests assessed the
effects of parameter changes on task performance: stimulus size, duration,
contrast, probability, inter-trial interval or inclusion of flanker distractors.
rCPT performance was also evaluated following acute administration of donepezil
(0-3 mg/kg, i.p.). RESULTS: C57BL/6J and DBA/2J mice showed similar acquisition
rates and final baseline performance following rCPT training. On probe tests,
rCPT performance of both strains was sensitive to alteration of visual and/or
attentional demands (stimulus size, duration, contrast, rate, flanker
distraction). Relative to C57BL/6J, DBA/2J mice exhibited (1) decreasing
sensitivity (d') across the 45-min session, (2) reduced performance on probes
where the appearance of stimuli or adjacent areas were changed (size, contrast,
flanking distractors) and (3) larger dose- and stimulus duration-dependent
changes in performance following donepezil administration. In contrast, CD1 mice
failed to acquire rCPT (stage 3) and pairwise visual discrimination tasks.
CONCLUSIONS: rCPT is a potentially useful translational tool for assessing
attention in mice and for detecting the effects of nootropic drugs.
PMID- 26415955
TI - Spontaneous poisoning by Hovenia dulcis in dairy cattle in Southwest Parana,
Brazil.
AB - Livestock poisoning by plants is a frequent occurrence which determines severe
losses, such as the fall in the milk and meat production, the cost of expensive
treatments, the state of immunosuppression, or even the animal's death. Cattle
ingest toxic plants only when there is food shortage, when they cannot select
what they eat, or when they ingest food for preference, which is the case of
Hovenia dulcis fruits, very rich in sucrose. This plant is widely distributed in
the southern and southeastern Brazilian regions. In literature, there are some
cases of severe human liver injury associated with a long-term of H. dulcis leaf
and fruit tea intake, and only one report regarding spontaneous poisoning of
goats caused by this plant ingestion. However, its toxic effects associated with
spontaneous ingestion by cattle have never been reported. This paper reports the
first case of spontaneous poisoning in cattle by H. dulcis, which occurred in a
dairy farm in southwest Parana, Brazil. Three cattle individuals showed anorexia,
ruminal atony, severe diarrhea and neurological tournament, head pressing,
blindness, ataxia, and circling. The necropsy of the animals was done, and the
remaining alterations were restricted to the digestive system and brain. The
clinical signs presented by the animals are characteristic of
polioencephalomalacia (PEM), caused by changes in the thiamine metabolism.
Furthermore, clinical signs, gross, and microscopic lesions as well as the large
amount of the plant throughout the digestive segment led to a diagnosis.
PMID- 26415957
TI - Cross-cultural perspectives on the patient-provider relationship: a qualitative
study exploring reflections from Ghanaian medical students following a clinical
rotation in the United States.
AB - BACKGROUND: In international health experiences, learners are exposed to
different culturally-based patient care models. Little is known about student
perceptions of patient-provider interactions when they travel from low-to high
resource settings. The purpose of this study was to explore these reflections
among a subset of Ghanaian medical students who participated in clinical
rotations at the University of Michigan Medical School (UMMS). METHODS: In-depth,
semi-structured interviews lasting 60-90 min were conducted with 15 individuals
who had participated in 3-to 4-week clinical rotations at UMMS between January
2008 and December 2011. Interviews were conducted from March to August 2012 and
transcribed verbatim, then independently coded by three investigators.
Investigators compared open codes and reached a consensus regarding major themes.
RESULTS: Participating Ghanaian medical students reported that their perspectives
of the patient-provider relationship were significantly affected by participation
in a UMMS rotation. Major thematic areas included: (1) observations of patient
care during the UMMS rotation, including patient comfort and privacy, physician
behavior toward patients, and patient behavior; (2) reflections on the role of
humanism and respect within patient care; (3) barriers to respectful care; and
(4) transformation of student behaviors and attitudes. Students also reported
integrating more patient-centered care into their own medical practice upon
return to Ghana DISCUSSION: Participation in a US-based clinical rotation has the
potential to introduce medical students from resource-limited settings to a
different paradigm of patient-provider interactions, which may impact their
future behavior and perspectives regarding patient care in their home countries.
CONCLUSIONS: Students from under-resourced settings can derive tremendous value
from participation in clinical electives in more affluent settings, namely
through exposure to a different type of medical care.
PMID- 26415958
TI - An organizational analysis of road traffic crash prevention to explain the
difficulties of a national program in a low income country.
AB - BACKGROUND: Road traffic crashes (RTC), that daily kill 3400 people and leave
15,000 with a permanent disability could be prevented through the implementation
of safety programs developed in partnership with governments and institutions.
The relationship between key stakeholders can be a crucial determinant to the
effectiveness of road safety programs. This issue has rarely been addressed. We
conducted a detailed organizational analysis of the stakeholders involved in road
safety programs in Lao People's Democratic Republic (Lao PDR). METHODS: A case
study was performed. The framework used was a snowball effect in which the
characterization of all key stakeholders and the links between them, as well as
the factors that led to these links, were determined. The effect of the relations
between key stakeholders on the prevention of RTC was assessed through an
analysis of the transactional, intangible and controlling factors that influence
these relationships. RESULTS: The design and implementation of road safety
programs in Lao PDR suffer from weak relationships between stakeholders and a
poorly functional bicephal leadership between the Ministry of Public Works and
Transport and the non-governmental organisation called Handicap International.
This poor coordination between key stakeholders is evident, particularly in the
area of collective action and is reinforced by a lack of interest from several
different stakeholders. Most agencies do not prioritize road safety. Uneven
distribution of funding is another contributing factor. Strengthening the
leadership is crucial to the success of the program. Some organisations have
skills, power the decision making and the allocation of resources in regards to
road safety programs. Encouraging participation of these organizations through a
more prominent position would thus result in a better collaboration. Non-monetary
rewards would further help to strengthen collaborative work. CONCLUSION: The
bicephal nature of the leadership of road safety programs proves detrimental, is
associated with a weak coalition between stakeholders, and contributes to the
declaimed poor effectiveness of the existing programs. The study has identified
non-monetary and realistic means of strengthening the collaboration between key
stakeholders. Stakeholders need to revise their interpretive schemes, in order to
actively support the reinforcement of government leadership of road safety
policies.
PMID- 26415959
TI - Associations between urbanicity and malaria at local scales in Uganda.
AB - BACKGROUND: Sub-Saharan Africa is expected to show the greatest rates of
urbanization over the next 50 years. Urbanization has shown a substantial impact
in reducing malaria transmission due to multiple factors, including unfavourable
habitats for Anopheles mosquitoes, generally healthier human populations, better
access to healthcare, and higher housing standards. Statistical relationships
have been explored at global and local scales, but generally only examining the
effects of urbanization on single malaria metrics. In this study, associations
between multiple measures of urbanization and a variety of malaria metrics were
estimated at local scales. METHODS: Cohorts of children and adults from 100
households across each of three contrasting sub-counties of Uganda (Walukuba,
Nagongera and Kihihi) were followed for 24 months. Measures of urbanicity
included density of surrounding households, vegetation index, satellite-derived
night-time lights, land cover, and a composite urbanicity score. Malaria metrics
included the household density of mosquitoes (number of female Anopheles
mosquitoes captured), parasite prevalence and malaria incidence. Associations
between measures of urbanicity and malaria metrics were made using negative
binomial and logistic regression models. RESULTS: One site (Walukuba) had
significantly higher urbanicity measures compared to the two rural sites. In
Walukuba, all individual measures of higher urbanicity were significantly
associated with a lower household density of mosquitoes. The higher composite
urbanicity score in Walukuba was also associated with a lower household density
of mosquitoes (incidence rate ratio = 0.28, 95 % CI 0.17-0.48, p < 0.001) and a
lower parasite prevalence (odds ratio, OR = 0.44, CI 0.20-0.97, p = 0.04). In one
rural site (Kihihi), only a higher density of surrounding households was
associated with a lower parasite prevalence (OR = 0.15, CI 0.07-0.34, p < 0.001).
And, in only one rural site (Nagongera) was living where NDVI <=0.45 associated
with higher incidence of malaria (IRR = 1.35, CI 1.35-1.70, p = 0.01).
CONCLUSIONS: Urbanicity has been shown previously to lead to a reduction in
malaria transmission at large spatial scales. At finer scales, individual
household measures of higher urbanicity were associated with lower mosquito
densities and parasite prevalence only in the site that was generally
characterized as being urban. The approaches outlined here can help better
characterize urbanicity at the household level and improve targeting of control
interventions.
PMID- 26415960
TI - Tonsillectomy reduces recurrence of IgA nephropathy in mesangial hypercellularity
type categorized by the Oxford classification.
AB - BACKGROUND: In patients with IgA nephropathy (IgAN), recurrence after steroid
pulse therapy is associated with reduced renal survival. However, the predictors
of recurrence have not yet been clarified. METHODS: All patients who received 6
month steroid pulse therapy from 2004 to 2010 in our four affiliated hospitals
and achieved a reduction of proteinuria to <0.4 g/day 1 year after treatment were
retrospectively evaluated. The primary outcome was proteinuria >=1.0 g/day during
follow-up or additional antiproteinuric therapy. Two histological classifications
were evaluated, the Oxford Classification with a split system and Japanese
histological grades (HGs) with a lumped system. RESULTS: During a median follow
up of 3.4 years, 27 (26.7 %) of the 101 patients showed recurrence. Multivariate
analysis showed that HG was the only significant predictor of recurrence, with HG
2+3+4 vs HG 1 having a hazard ratio of 7.38 (95 % confidence interval 1.52-133).
Furthermore, in patients with mesangial hypercellularity according to the Oxford
Classification, cumulative rate of recurrence-free survival was greater in
patients with steroid therapy plus tonsillectomy compared with those who received
steroid therapy alone (Log-rank test, P = 0.022). However, this association was
not observed in patients without mesangial hypercellularity. CONCLUSIONS: HG is a
novel predictor of recurrence after steroid pulse therapy in patients with IgAN.
Moreover, the combination of steroid pulse therapy plus tonsillectomy may
indicate a lower risk of recurrence in patients with mesangial hypercellularity,
as defined by the Oxford Classification.
PMID- 26415961
TI - Using realist review to inform intervention development: methodological
illustration and conceptual platform for collaborative care in offender mental
health.
AB - BACKGROUND: This paper reports how we used a realist review, as part of a wider
project to improve collaborative mental health care for prisoners with common
mental health problems, to develop a conceptual platform. The importance of
offenders gaining support for their mental health, and the need for practitioners
across the health service, the criminal justice system, and the third sector to
work together to achieve this is recognised internationally. However, the
literature does not provide coherent analyses of how these ambitions can be
achieved. This paper demonstrates how a realist review can be applied to inform
complex intervention development that spans different locations, organisations,
professions, and care sectors. METHODS: We applied and developed a realist review
for the purposes of intervention development, using a three-stage process. (1) An
iterative database search strategy (extending beyond criminal justice and
offender health) and groups of academics, practitioners, and people with lived
experience were used to identify explanatory accounts (n = 347). (2) From these
accounts, we developed consolidated explanatory accounts (n = 75). (3) The
identified interactions between practitioners and offenders (within their
organisational, social, and cultural contexts) were specified in a conceptual
platform. We also specify, step by step, how these explanatory accounts were
documented, consolidated, and built into a conceptual platform. This addresses an
important methodological gap for social scientists and intervention developers
about how to develop and articulate programme and implementation theory
underpinning complex interventions. RESULTS: An integrated person-centred system
is proposed to improve collaborative mental health care for offenders with common
mental health problems (near to and after release) by achieving consistency
between the goals of different sectors and practitioners, enabling practitioners
to apply scientific and experiential knowledge in working judiciously and
reflectively, and building systems and aligning resources that are centred on
offenders' health and social care needs. CONCLUSIONS: As part of a broader
programme of work, a realist review can make an important contribution to the
specification of theoretically informed interventions that have the potential to
improve health outcomes. Our conceptual platform has potential application in
related systems of health and social care where integrated, and person-centred
care is a goal.
PMID- 26415962
TI - Let it be? Pain control attempts critically amplify attention to somatosensory
input.
AB - Recent studies have suggested that the threat of pain may redirect attention
towards specific features of the pain stimulus via attentional control settings.
For instance, it has been shown that anticipating pain results in attentional
prioritization of the location where pain is expected. In contemporary theories
on attention and pain, it has been argued that pain control motivation-e.g.,
attempting to avoid pain-is capable of enhancing these effects. The present study
investigated if the threat of pain prioritizes attention towards somatosensory
input over other sensory information, and if pursuing a pain control goal
augments this effect. In a Temporal Order Judgment experiment, 41 participants
were presented with visuo-tactile stimulus pairs and asked to judge which
stimulus they had perceived first. Half of all trials were associated with the
threat of acute pain, while the other half was not. Furthermore, half of our
sample was encouraged to avoid the administration of pain by means of a specified
behavioral response, whereas the other half was not. In line with our hypotheses,
we found the threat of pain to prioritize attention towards the somatosensory
modality, i.e., participants tended to perceive the tactile stimulus as occurring
earlier in time than the visual stimulus. Interestingly, in-depth analyses
suggested that this effect was predominantly carried by participants who were
engaged in pain control efforts. These findings support the idea that pain goals
exert top-down attentional control prioritizing pain-relevant sensory
information. Clinical relevance and future directions are discussed.
PMID- 26415963
TI - Cell culture on hydrophilicity-controlled silicon nitride surfaces.
AB - Cell culture on silicon nitride membranes is required for atmospheric scanning
electron microscopy, electron beam excitation assisted optical microscopy, and
various biological sensors. Cell adhesion to silicon nitride membranes is
typically weak, and cell proliferation is limited. We increased the adhesion
force and proliferation of cultured HeLa cells by controlling the surface
hydrophilicity of silicon nitride membranes. We covalently coupled carboxyl
groups on silicon nitride membranes, and measured the contact angles of water
droplets on the surfaces to evaluate the hydrophilicity. We cultured HeLa cells
on the coated membranes and evaluated stretch of the cell. Cell migration and
confluence were observed on the coated silicon nitride films. We also
demonstrated preliminary observation result with direct electron beam excitation
assisted optical microscope.
PMID- 26415964
TI - Assessment of heavy metal pollution in Cordoba (Spain) by biomonitoring foraging
honeybee.
AB - Due to features that make them outstanding environmental bioindicator, colonies
of Apis mellifera are being used to study environmental pollution. The primary
objective of this research was to use honeybee colonies to identify heavy metals
and determine their utility for environmental management. Five stations each with
two A. mellifera hives were strategically located in urban, industrial,
agricultural and forested areas within the municipality of Cordoba (Spain), and
foraging bees were collected from April to December in 2007, 2009 and 2010 to
analyse spatial and temporal variation in Pb, Cr, Ni and Cd pollution. Metal
concentrations, in milligram per kilogram of honeybee, were determined by
inductively coupled plasma-atomic emission spectrometry and graphite furnace
atomic absorption spectrophotometry. Significant differences in concentrations
were found among the various locations and periods. The highest number of values
exceeding the upper reference thresholds proposed for this study (Pb, 0.7 mg/kg;
Cr, 0.12 mg/kg; Ni, 0.3 mg/kg; and Cd, 0.1 mg/kg) was observed for Pb and Cr
(6.25% respectively), station S4 (13.22%), year 2007 (20.83%) and in months of
May and July (11.90% each). Regarding the Cd, which was analysed only in 2010,
the highest number of values exceeding the upper reference thresholds was 40%.
Biomonitoring with colonies of A. mellifera could contribute to improved
surveillance and control systems for atmospheric pollution by integrating
qualitative and quantitative assessments, thus facilitating prevention and
readiness in the event of environmental crises.
PMID- 26415965
TI - methylPipe and compEpiTools: a suite of R packages for the integrative analysis
of epigenomics data.
AB - BACKGROUND: Numerous methods are available to profile several epigenetic marks,
providing data with different genome coverage and resolution. Large epigenomic
datasets are then generated, and often combined with other high-throughput data,
including RNA-seq, ChIP-seq for transcription factors (TFs) binding and DNase-seq
experiments. Despite the numerous computational tools covering specific steps in
the analysis of large-scale epigenomics data, comprehensive software solutions
for their integrative analysis are still missing. Multiple tools must be
identified and combined to jointly analyze histone marks, TFs binding and other
omics data together with DNA methylation data, complicating the analysis of these
data and their integration with publicly available datasets. RESULTS: To overcome
the burden of integrating various data types with multiple tools, we developed
two companion R/Bioconductor packages. The former, methylPipe, is tailored to the
analysis of high- or low-resolution DNA methylomes in several species,
accommodating (hydroxy-)methyl-cytosines in both CpG and non-CpG sequence
context. The analysis of multiple whole-genome bisulfite sequencing experiments
is supported, while maintaining the ability of integrating targeted genomic data.
The latter, compEpiTools, seamlessly incorporates the results obtained with
methylPipe and supports their integration with other epigenomics data. It
provides a number of methods to score these data in regions of interest, leading
to the identification of enhancers, lncRNAs, and RNAPII stalling/elongation
dynamics. Moreover, it allows a fast and comprehensive annotation of the
resulting genomic regions, and the association of the corresponding genes with
non-redundant GeneOntology terms. Finally, the package includes a flexible method
based on heatmaps for the integration of various data types, combining annotation
tracks with continuous or categorical data tracks. CONCLUSIONS: methylPipe and
compEpiTools provide a comprehensive Bioconductor-compliant solution for the
integrative analysis of heterogeneous epigenomics data. These packages are
instrumental in providing biologists with minimal R skills a complete toolkit
facilitating the analysis of their own data, or in accelerating the analyses
performed by more experienced bioinformaticians.
PMID- 26415966
TI - Ketamine and other glutamate receptor modulators for depression in bipolar
disorder in adults.
AB - BACKGROUND: There is emerging evidence that glutamatergic system dysfunction
might play an important role in the pathophysiology of bipolar depression. This
review focuses on the use of glutamate receptor modulators for depression in
bipolar disorder. OBJECTIVES: 1. To assess the effects of ketamine and other
glutamate receptor modulators in alleviating the acute symptoms of depression in
people with bipolar disorder.2. To review the acceptability of ketamine and other
glutamate receptor modulators in people with bipolar disorder who are
experiencing acute depression symptoms. SEARCH METHODS: We searched the Cochrane
Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR,
to 9 January 2015). This register includes relevant randomised controlled trials
(RCTs) from: the Cochrane Library (all years), MEDLINE (1950 to date), EMBASE
(1974 to date), and PsycINFO (1967 to date). We cross-checked reference lists of
relevant papers and systematic reviews. We did not apply any restrictions to
date, language or publication status. SELECTION CRITERIA: Randomised controlled
trials (RCTs) comparing ketamine, memantine, or other glutamate receptor
modulators with other active psychotropic drugs or saline placebo in adults with
bipolar depression. DATA COLLECTION AND ANALYSIS: At least two review authors
independently selected studies for inclusion, assessed trial quality and
extracted data. Primary outcomes for this review were response rate and adverse
events. Secondary outcomes included remission rate, depression severity change
scores, suicidality, cognition, quality of life, and dropout rate. We contacted
study authors for additional information. MAIN RESULTS: Five studies (329
participants) were included in this review. All included studies were placebo
controlled and two-armed, and the glutamate receptor modulators - ketamine (two
trials), memantine (two trials), and cytidine (one trial) - were used as add-on
drugs to mood stabilisers. The treatment period ranged from a single intravenous
administration (all ketamine studies), to repeated administration for memantine
and cytidine (8 to 12 weeks, and 12 weeks, respectively). Three of the studies
took place in the USA, one in Taiwan, and in one, the location was unclear. The
majority (70.5%) of participants were from Taiwan. All participants had a primary
diagnosis of bipolar disorder, according to the DSM-IV or DSM-IV-TR, and were in
a current depressive phase. The severity of depression was at least moderate in
all but one study.Among all glutamate receptor modulators included in this
review, only ketamine appeared to be more efficacious than placebo 24 hours after
the infusion for the primary outcome, response rate (odds ratio (OR) 11.61, 95%
confidence interval (CI) 1.25 to 107.74; P = 0.03; I2 = 0%, 2 studies, 33
participants). This evidence was rated as low quality. The statistically
significant difference disappeared at three days, but the mean estimate still
favoured ketamine (OR 8.24, 95% CI 0.84 to 80.61; 2 studies, 33 participants;
very low quality evidence). We found no difference in response between ketamine
and placebo at one week (OR 4.00, 95% CI 0.33 to 48.66; P = 0.28, 1 study; 18
participants; very low quality evidence).There was no significant difference
between memantine and placebo in response rate one week after treatment (OR 1.08,
95% CI 0.06 to 19.05; P = 0.96, 1 study, 29 participants), two weeks (OR 4.88,
95% CI 0.78 to 30.29; P = 0.09, 1 study, 29 participants), four weeks (OR 5.33,
95% CI 1.02 to 27.76; P = 0.05, 1 study, 29 participants), or at three months
(OR, 1.66, 95% CI 0.69 to 4.03; P = 0.26, I2 = 36%, 2 studies, 261 participants).
These findings were based on very low quality evidence.There was no significant
difference between cytidine and placebo in response rate at three months (OR,
1.13, 95% CI 0.30 to 4.24; P = 0.86, 1 study, 35 participants; very low quality
evidence).For the secondary outcome of remission, no significant differences were
found between ketamine and placebo, nor between memantine and placebo. For the
secondary outcome of change scores from baseline on depression scales, ketamine
was more effective than placebo at 24 hours (MD -11.81, 95% CI -20.01 to -3.61; P
= 0.005, 2 studies, 32 participants) but not at one or two weeks after treatment.
There was no difference between memantine and placebo for this outcome.We found
no significant differences in terms of adverse events between placebo and
ketamine, memantine, or cytidine. There were no differences between ketamine and
placebo, memantine and placebo, or cytidine and placebo in total dropouts. No
data were available on dropouts due to adverse effects for ketamine or cytidine;
but no difference was found between memantine and placebo. AUTHORS' CONCLUSIONS:
Reliable conclusions from this review are severely limited by the small amount of
data usable for analysis. The body of evidence about glutamate receptor
modulators in bipolar disorder is even smaller than that which is available for
unipolar depression. Overall, we found limited evidence in favour of a single
intravenous dose of ketamine (as add-on therapy to mood stabilisers) over placebo
in terms of response rate up to 24 hours; ketamine did not show any better
efficacy in terms of remission in bipolar depression. Even though ketamine has
the potential to have a rapid and transient antidepressant effect, the efficacy
of a single intravenous dose may be limited. Ketamine's psychotomimetic effects
could compromise study blinding; this is a particular issue for this review as no
included study used an active comparator, and so we cannot rule out the potential
bias introduced by inadequate blinding procedures.We did not find conclusive
evidence on adverse events with ketamine. To draw more robust conclusions,
further RCTs (with adequate blinding) are needed to explore different modes of
administration of ketamine and to study different methods of sustaining
antidepressant response, such as repeated administrations. There was not enough
evidence to draw meaningful conclusions for the remaining two glutamate receptor
modulators (memantine and cytidine). This review is limited not only by
completeness of evidence, but also by the low to very low quality of the
available evidence.
PMID- 26415967
TI - Beyond the Audiology Clinic: Innovations and Possibilities of Connected Health.
PMID- 26415969
TI - Innovations and Possibilities in Connected Health.
AB - BACKGROUND: Health care is being fundamentally changed by telemedicine.
Telemedicine uses communication technologies in prevention, disease management,
home health care, long-term (chronic) care, emergency medicine, and many other
applications including audiology. Telemedicine is being adopted and integrated
into the health care enterprise at an exponential rate and it is often difficult
to keep up with all of these changes. Other key drivers such as the Affordable
Care Act and other federal health care initiatives are pushing the adoption of
telemedicine and catalyzing a flood of interest in telemedicine, telehealth, and
m-Health. PURPOSE: This paper provides an overview of telehealth models and will
describe methodologies as they pertain to clinical practice. The goal is to
provide the principles behind the practice of telemedicine and how they can be
applied to teleaudiology programs. There is a very large body of evidence
supporting the benefits and utility of telehealth in terms of technology,
economic value, and impact on patients. However, there are still barriers to
acceptance, so we must address these challenges and involve all relevant
stakeholders if telehealth is to become an integral part of the health care
system. Clinical guidelines for telemedicine developed by experts who are
practicing it on a daily basis is one way to help overcome these barriers, so
attention will be devoted to a discussion of current guidelines. CONCLUSIONS:
Telemedicine is not a unique clinical specialty, but rather uses
telecommunication technologies to reach out to patients to reduce barriers to
care in underserved areas, improve patient care and accessibility to specialists,
decrease professional isolation in rural areas, help medical practitioners expand
their practice reach, and save patients from having to travel or be transported
to receive high quality care.
PMID- 26415968
TI - A Store-and-Forward Tele-Audiology Solution to Promote Efficient Screenings for
Ototoxicity during Cisplatin Cancer Treatment.
AB - BACKGROUND: Tele-audiology improves access, controls cost, and improves
efficiency of many aspects within health care. We have developed and validated a
device, the ototoxicity identification device (OtoID), which enables remote
hearing monitoring by a patient during chemotherapy treatment. Aspects of the
design such as patient self-testing and texting of results to the audiology
clinic are important features of this device. PURPOSE: The purpose of this
article is to present the efficacy and effectiveness of the OtoID hearing
screener. RESEARCH DESIGN: A repeated measures design was used in this study.
STUDY SAMPLE: Twenty-one veterans undergoing cisplatin chemotherapy were
recruited in this study. DATA COLLECTION AND ANALYSIS: Participants were tested
using the OtoID at each cisplatin treatment by an audiologist using the manual
mode of test and the participant using the automated mode of test. Test
sensitivity and specificity were developed from the detection (yes/no) of an
American Speech-Language-Hearing Association (ASHA) change in hearing. RESULTS:
The OtoID had a test sensitivity of 80.6% and specificity of 85.3%. A logistic
regression model analysis of the probability of an ASHA shift identified by the
automated OtoID was conducted. Separate models were fit to establish effects of
age, average baseline thresholds in the sensitive range for ototoxicity (SRO),
and dose of cisplatin on the probability of a positive hearing change result.
Interactions were also included to evaluate these effects on the sensitivity and
false-positive rates of the automated test. Results indicated no statistically
significant effects of age, of baseline hearing in the SRO frequencies, or of
cisplatin dose. CONCLUSIONS: The OtoID automated test can be recommended for use.
The automated test provides significant personnel efficiencies. The modem with
simple text messaging function recently added to the device improves on these
efficiencies.
PMID- 26415971
TI - Ubiquitous Real-World Sensing and Audiology-Based Health Informatics.
AB - BACKGROUND: Hearing impairment and hearing rehabilitation strategies have
historically been studied within the confines of a sound booth under controlled
experimental conditions. The real world is quite different from the clinical
setting and it is important to study how a person with hearing impairment
interacts with the world both with and without a hearing assist intervention. A
person's ability to hear enables them to communicate and to effectively interact
with the world. If a person suffers from hearing impairment, we might anticipate
that they could become more disengaged from the world, more socially isolated,
potentially depressed, and have additional comorbidities such as cognitive and
physical impairment. Indeed, prior research has shown that hearing impairment is
associated with social isolation, decreased functional ability and mobility, fall
risk, diabetes, and cognitive impairment. However, nearly all of the work that
has been done in this area of assessing the impact of hearing impairment on a
person's social, cognitive, and physical health has been done through clinical
tests or self-report studies using questionnaires and surveys that attempt to
objectively quantify various aspects of health. Unfortunately, clinical tests,
questionnaires, and surveys oftentimes inaccurately assess a person's true
social, cognitive, and physical health. Only when a person is observed in their
natural living environment can a more accurate assessment of health be obtained.
The ability to assess hearing health, social engagement, cognitive, and physical
health in natural living environments is becoming possible with the advent of
ubiquitous sensing capabilities. PURPOSE: Here we discuss some of the work that
has been done by our group and others that may be of use to the field of
audiology e-health. The purpose of this article is not to present new
experimental data, but rather to describe a new method of using advanced in-home
sensing techniques to better understand how hearing diagnostics, interventions,
and rehabilitation influence the lives and behaviors of patients.
PMID- 26415970
TI - Connected Audiological Rehabilitation: 21st Century Innovations.
AB - BACKGROUND: Tele-audiology provides a means to offer audiologic rehabilitation
(AR) in a cost-, resource-, and time-effective manner. If designed appropriately,
it also has the capability of personalizing rehabilitation to the user in terms
of content, depth of detail, etc., thus permitting selection of the best content
for a particular individual. Synchronous/real-time data collection, store and
forward telehealth, remote monitoring and mobile health using smartphone
applications have each been applied to components of audiologic rehabilitation
intervention (sensory management, instruction in the use of technology and
control of the listening environment, perceptual and communication strategies
training, and counseling). In this article, the current state of tele
audiological rehabilitation interventions are described and discussed. RESULTS:
The provision of AR via tele-audiology potentially provides a cost-effective
mechanism for addressing barriers to the routine provision of AR beyond
provisions of hearing technology. Furthermore, if designed appropriately, it has
the capability of personalizing rehabilitation to the user in terms of content,
depth of detail, etc., thus permitting selection of the best content for a
particular individual. However, effective widespread implementation of tele
audiology will be dependent on good education of patients and clinician alike,
and researchers must continue to examine the effectiveness of these new
approaches to AR in order to ensure clinicians provide effective evidence-based
rehabilitation to their patients. CONCLUSIONS: While several barriers to the
widespread use of tele-audiology for audiologic rehabilitation currently exist,
it is concluded that through education of patients and clinicians alike, it will
gain greater support from practitioners and patients over time and will become
successfully and widely implemented.
PMID- 26415972
TI - The Acoustic Test Environment for Hearing Testing.
AB - BACKGROUND: Audiology clinics traditionally employ expensive, prefabricated sound
rooms to create an environment that is sufficiently quiet for accurate hearing
tests. There is seldom any analysis of the need for or benefit from such
enclosures. There may be less expensive methods that would decrease the cost of
and increase access to hearing testing. PURPOSE: This report provides information
concerning the need for and effectiveness of sound rooms and an analysis of the
audiometric test ranges for various earphone/room combinations. RESEARCH DESIGN:
Acoustic measurements made in four rooms were analyzed with the attenuation
provided by various earphone designs to determine the maximum permissible ambient
noise levels and the corresponding audiometric test ranges. STUDY SAMPLE: The
measurements and calculations were performed with four test rooms and five
earphone designs. DATA COLLECTION AND ANALYSIS: Ambient noise levels and earphone
attenuation characteristics were used to calculate the noise levels that reach
the ear. Those were compared to the maximum permissible ambient noise levels that
are provided in ANSI S3.1-1999 or calculated from measured attenuation levels.
These measurements were used to calculate testable ranges for each room/earphone
combination. RESULTS: The various room/earphone combinations resulted in minimum
test levels that ranged from -10 to 20 dB HL at various test frequencies.
CONCLUSIONS: When the actual benefits of expensive prefabricated sound rooms are
assessed based on the range of hearing levels that can be tested, the
effectiveness of that approach becomes highly questionable. Less expensive
methods based on planning the clinic space, use of inexpensive sound treatments,
and selecting an appropriate earphone can be effective in almost any space that
would be used for hearing testing.
PMID- 26415973
TI - Tele-audiology: Expanding Access to Hearing Care and Enhancing Patient
Connectivity.
AB - BACKGROUND: Tele-audiology within the Department of Veterans Affairs has expanded
significantly in response to growing Veteran hearing needs and issues, namely
maldistribution of provider resources and continued lags in timely access to
care. Although tele-audiology originated from successive telemedicine programs
dating back to the early 1960s, the innovation that is currently being developed
broadens tele-audiology and hearing care practice to virtual care modalities such
as clinical video telehealth, store-and-forward telehealth, home telehealth,
mobile health applications, secure messaging, and electronic consults. PURPOSE:
The purpose of this article is to address current and emerging tele-audiology
initiatives in context of a connected health care practice model. It includes
information on initiatives within the Department of Veterans Affairs, provides an
overview of current and potential modalities for improving patient hearing care,
and identifies the challenges that exist in implementing and sustaining these
services. Information is intended to stimulate creative thinking about future
innovative service delivery models. CONCLUSION: Significant challenges exist in
the evolution of innovative tele-audiology services. Despite barriers, these
initiatives have the potential to match existing capacity with emerging patient
demands in a mutually beneficial partnership and can be successfully integrated
into diverse health care and private sector organizations.
PMID- 26415976
TI - Interplay between histone H1 structure and function.
AB - H1 linker histones are involved both in the maintenance of higher-order chromatin
structure and in gene regulation. Histone H1 exists in multiple isoforms, is
evolutionarily variable and undergoes a large variety of post-translational
modifications. We review recent progress in the understanding of the folding and
structure of histone H1 domains with an emphasis on the interactions with DNA.
The importance of intrinsic disorder and hydrophobic interactions in the folding
and function of the carboxy-terminal domain (CTD) is discussed. The induction of
a molten globule-state in the CTD by macromolecular crowding is also considered.
The effects of phosphorylation by cyclin-dependent kinases on the structure of
the CTD, as well as on chromatin condensation and oligomerization, are described.
We also address the extranuclear functions of histone H1, including the
interaction with the beta-amyloid peptide.
PMID- 26415975
TI - Alzheimer's Disease Risk and Progression: The Role of Nutritional Supplements and
their Effect on Drug Therapy Outcome.
AB - Alzheimer's disease (AD) is the most common neurodegenerative disease in the
elderly population. Despite significant advancements in understanding the genetic
and molecular basis of AD, the pathology still lacks treatments that can slow
down or reverse the progression of cognitive deterioration. Recently, the
relationship between nutrient deficiency and dementia onset has been highlighted.
AD is in fact a multifactorial pathology, so that a multi-target approach using
combinations of micronutrients and drugs could have beneficial effects on
cognitive function in neurodegenerative brain disorders leading to synaptic
degeneration. Primarily, this review examines the most recent literature
regarding the effects of nutrition on the risk/progression of the disease,
focusing attention mostly on antioxidants agents, polyunsaturated fatty acids and
metals. Secondly, it aims to figure out if nutritional supplements might have
beneficial effects on drug therapy outcome. Even if nutritional supplements
showed contrasting evidence of a likely effect of decreasing the risk of AD onset
that could be studied more deeply in other clinical trials, no convincing data
are present about their usefulness in combination with drug therapies and their
effectiveness in slowing down the disease progression.
PMID- 26415977
TI - My gut feeling says rest: Increased intestinal permeability contributes to
chronic diseases in high-intensity exercisers.
AB - Chronic diseases are the leading cause of death and disability worldwide, and
many of these conditions are linked to chronic inflammation. One potential cause
of chronic inflammation is an increased intestinal epithelial permeability.
Recent studies have demonstrated that parasympathetic stimulation via the
efferent abdominal vagus nerve increases the expression and proper localization
of tight junction proteins and decreases intestinal epithelial permeability. This
finding may provide a novel approach for treating and preventing many chronic
conditions. Importantly, physical activity is associated with increased resting
parasympathetic (vagal) activity and lower risk of chronic diseases. However,
high intensity long duration exercise can be harmful to overall health.
Specifically, individuals who frequently exercise strenuously and for longer time
intervals have the same mortality rates as sedentary individuals. This may be
explained, in part, by longer periods of reduced vagal activity as vagal activity
is markedly reduced both during and after intense exercise. We hypothesize that
one mechanism by which exercise provides its health benefits is by increasing
resting vagal activity and decreasing intestinal epithelial permeability, thus
decreasing chronic inflammation. Additionally, we hypothesize that long periods
of reduced vagal activity in individuals who exercise at high intensities and for
longer durations, decrease the integrity of the intestinal barrier, putting them
at greater risk of chronic inflammation and a host of chronic diseases. Thus,
this hypothesis provides a conceptual link between the well-established benefits
of frequent exercise and the paradoxical deleterious effects of prolonged, high
intensity exercise without adequate rest.
PMID- 26415978
TI - Nitrates are safe in patients with glaucoma.
PMID- 26415979
TI - beta-elemene inhibits monocyte-endothelial cells interactions via reactive oxygen
species/MAPK/NF-kappaB signaling pathway in vitro.
AB - The recruitment of monocytes to the active endothelial cells is an early step in
the formation of atherosclerotic lesions; therefore, the inhibition of monocyte
endothelial cells interactions may serve as a potential therapeutic strategy for
atherosclerosis. Recent studies suggest that beta-elemene can protect against
atherosclerosis in vivo and vitro; however, the mechanism underlying the anti
atherosclerotic effect by beta-elemene is not clear yet. In this study, we aimed
to investigate the effects of beta-elemene on the monocyte-endothelial cells
interactions in the initiation of atherosclerosis in vitro. Our results showed
that beta-elemene protects human umbilical vein endothelial cells (HUVECs) from
hydrogen peroxide-induced endothelial cells injury in vitro. Besides, this
molecule inhibits monocyte adhesion and transendothelial migration across
inflamed endothelium through the suppression of the nuclear factor-kappa B
dependent expression of cell adhesion molecules. Further, beta-elemene decreases
generation of reactive oxygen species (ROS) and prevents the activation of
mitogen-activated protein kinase (MAPK) signaling pathway in HUVECs. In
conclusion, this study would provide a new pharmacological evidence of the
significance of beta-elemene as a future drug for prevention and treatment of
atherosclerosis.
PMID- 26415980
TI - Inhibitory effect of fluvoxamine on beta-casein expression via a serotonin
independent mechanism in human mammary epithelial cells.
AB - Selective serotonin reuptake inhibitors (SSRIs) are widely used as a first-line
therapy in postpartum depression. The objective of this study was to determine
the mechanism underlying the inhibitory effects of the SSRI, fluvoxamine, on beta
casein expression, an indicator of lactation, in MCF-12A human mammary epithelial
cells. Expression levels of serotonin (5-hydroxytryptamine; 5-HT) transporter, an
SSRI target protein, and tryptophan hydroxylase 1, a rate-limiting enzyme in 5-HT
biosynthesis, were increased in MCF-12A cells by prolactin treatment. Treatment
with 1 MUM fluvoxamine for 72 h significantly decreased protein levels of beta
casein and phosphorylated signal transducer and activator transcription 5
(pSTAT5). Extracellular 5-HT levels were significantly increased after exposure
to 1 MUM fluvoxamine, in comparison with those of untreated and vehicle-treated
cells; however, extracellular 5-HT had little effect on the decrease in beta
casein expression. Expression of glucose-related protein 78/binding
immunoglobulin protein, a regulator of endoplasmic reticulum (ER) stress, was
significantly increased after treatment with 1 MUM fluvoxamine for 48 h. Exposure
to tunicamycin, an inducer of ER stress, also decreased expression of beta-casein
and pSTAT5 in a manner similar to fluvoxamine. Our results indicate that
fluvoxamine suppresses beta-casein expression in MCF-12A cells via inhibition of
STAT5 phosphorylation caused by induction of ER stress. Further studies are
required to confirm the effect of fluvoxamine on the function of mammary
epithelial cells.
PMID- 26415981
TI - Endogenous oestrogens do not regulate endothelial nitric oxide production in
early postnatal rats.
AB - Previously we showed that endothelium of 1-2-weeks old rats exerts an
anticontractile effect due to spontaneous NO production which correlates with a
higher eNOS expression level compared to adult rats. Oestrogens are powerful
regulators of eNOS expression and activity in arterial endothelium. This study
tested the hypothesis that anticontractile influence of endothelium in young rats
is regulated by endogenous oestrogens. Wistar rats were daily treated with ICI
182,780 or letrozole (oestrogen receptor antagonist and aromatase inhibitor,
respectively; s.c., 1mg/kg/day) from the second postnatal day, control pups
received vehicle injections. At the age of 10-12-days we studied contraction of
saphenous arteries using wire myography. ELISA and qPCR were used to evaluate
blood sex steroids levels and mRNA expression in arterial tissue, respectively.
Ten-12 days old male rats compared to adult male rats demonstrated 78% higher
serum 17beta-oestradiol concentration and several-fold increase in mRNA contents
of oestrogen receptors (ERalpha and GPER1). However, treatments with ICI 182,780
or letrozole did not affect arterial sensitivity to methoxamine (alpha1
adrenoceptor agonist) in 10-12-days old males. The blockade of NO-synthase with L
NNA caused tonic contraction and potentiated the response to methoxamine, these
effects were similar in control and both treated groups. The sensitivity of
endothelium-denuded saphenous arteries to NO-donor DEA/NO did not differ between
control and treated groups as well. In addition, treatments with ICI 182,780 or
letrozole did not change eNOS expression level in arterial tissue. Our results
suggest that endogenous oestrogens do not regulate anticontractile effect of NO
during early postnatal development in rats.
PMID- 26415982
TI - The adenosine A2A receptor antagonist, istradefylline enhances anti-parkinsonian
activity induced by combined treatment with low doses of L-DOPA and dopamine
agonists in MPTP-treated common marmosets.
AB - The adenosine A2A receptor antagonist, istradefylline improves motor function in
patients with advanced Parkinson's disease (PD) optimally treated with a
combination of L-DOPA and a dopamine agonist without increasing the risk of
troublesome dyskinesia. However, the effects of istradefylline on motor function
when administered in combination with low dose of L-DOPA and dopamine agonists as
occurs in early PD are unknown. We investigated whether istradefylline enhances
the combined anti-parkinsonian effects of a suboptimal dose of L-DOPA and a
threshold dose of either the non-ergot dopamine agonist, ropinirole or the ergot
dopamine agonist, pergolide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-treated common marmoset. Threshold doses of ropinirole (0.025-0.075 mg/kg
p.o.) and pergolide (0.01 mg/kg p.o.) produced a weak anti-parkinsonian effect.
Co-administration of a suboptimal dose of L-DOPA (2.5mg/kg p.o.) with threshold
doses of the dopamine agonists enhanced their anti-parkinsonian effect that led
to increased 'ON' time without dyskinesia appearing. Administering istradefylline
(10mg/kg p.o.) with the threshold doses of dopamine agonists and the suboptimal
dose of L-DOPA in a triple combination caused a further enhancement of the anti
parkinsonian response but dyskinesia was still absent. In early PD, dopamine
agonists are often used as first-line monotherapy, but efficacy is usually lost
within a few years, at which time L-DOPA is added but with the risk of dyskinesia
appearance. These results show that istradefylline is effective in improving
motor function in combination with low dose dopaminergic drug treatment without
provoking dyskinesia.
PMID- 26415983
TI - Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the
function of bone marrow-derived dendritic cells and the effects of CP-25.
AB - This study was to investigate PGE2 and TNF-alpha signaling pathway involving in
the maturation and activation of bone marrow dendritic cells (DCs) and the effect
of CP-25. Bone marrow DCs were isolated and stimulated by PGE2 and TNF-alpha
respectively. The markers of maturation and activation expressed on DCs, such as
CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were
analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs,
the signaling pathways of PGE2-EP4-cAMP and TNF-alpha-TRADD-TRAF2-NF-kappaB in
DCs were analyzed. The results showed that both PGE2 and TNF-alpha up-regulated
the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen
uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell
proliferation. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased significantly
the expressions of CD40, CD80, CD83, CD86 and MHC-II, increased the antigen
uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased
the expressions of EP4, NF-kappaB and down-regulated cAMP level of DCs. TNF-alpha
could also up-regulate TNFR1, TRADD, TRAF2, and NF-kappaB expression of DCs. CP
25 (10(-5), 10(-6), and 10(-7)mol/l) decreased the expressions of EP4 and NF
kappaB, increased cAMP level in DCs stimulated by PGE2. CP-25 (10(-5), 10(-6),
and 10(-7)mol/l) also could down-regulate significantly TNFR1, TRADD, TRAF2, and
NF-kappaB expression in DCs stimulated by TNF-alpha. These results demonstrate
that PGE2 and TNF-alpha could enhance DCs functions by mediating PGE2-EP4-cAMP
pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-kappaB pathway respectively. CP-25 might
inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1
TRADD-TRAF2-NF-kappaB pathways.
PMID- 26415984
TI - Pd2Au36(SR)24 cluster: structure studies.
AB - The location of the Pd atoms in Pd2Au36(SC2H4Ph)24, is studied both
experimentally and theoretically. X-ray photoelectron spectroscopy (XPS)
indicates oxidized Pd atoms. Palladium K-edge extended X-ray absorption fine
structure (EXAFS) data clearly show Pd-S bonds, which is supported by far
infrared spectroscopy and by comparing theoretical EXAFS spectra in R space and
circular dichroism spectra of the staple, surface and core doped structures with
experimental spectra.
PMID- 26415986
TI - Effect of co-administration of probiotics with polysaccharide based colon
targeted delivery systems to optimize site specific drug release.
AB - Significant clinical success of colon targeted dosage forms has been limited by
their inappropriate release profile at the target site. Their failure to release
the drug completely in the colon may be attributed to changes in the colonic
milieu because of pathological state, drug effect and psychological stress
accompanying the diseased state or, a combination of these. Alteration in normal
colonic pH and bacterial picture leads to incomplete release of drug from the
designed delivery system. We report the effectiveness of a targeted delivery
system wherein the constant replenishment of the colonic microbiota is achieved
by concomitant administration of probiotics along with the polysaccharide based
drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared.
In the dissolution studies, these spheroids showed markedly higher release in the
simulated colonic fluid. In vivo experiments conducted in rats clearly
demonstrated the therapeutic advantage of co-administration of probiotics with
guar gum coated spheroids. Our results suggest that concomitant use of probiotics
along with the polysaccharide based delivery systems can be a simple strategy to
achieve satisfactory colon targeting of drugs.
PMID- 26415985
TI - Coordinating activation strategy for C(sp(3))-H/C(sp(3))-H cross-coupling to
access beta-aromatic alpha-amino acids.
AB - The past decade has witnessed significant advances in C-H bond functionalizations
with the discovery of new mechanisms. Non-precious transition-metal-catalysed
radical oxidative coupling for C(sp(3))-H bond transformations is an appealing
strategy for C-C bond formations. The radical oxidative C(sp(3))-H/C(sp(3))-H
cross-coupling reactions of alpha-C(sp(3))-H bonds of amines with free radicals
represent a conceptual and practical challenge. We herein develop the
coordinating activation strategy to illustrate the nickel-catalysed radical
oxidative cross-coupling between C(sp(3))-H bonds and (hetero)arylmethyl free
radicals. The protocol can tolerate a rich variety of alpha-amino acids and
(hetero)arylmethanes as well as arylmethylenes and arylmethines, affording a
large library of alpha-tertiary and alpha-quaternary beta-aromatic alpha-amino
acids. This process also features low-cost metal catalyst, readily handled and
easily removable coordinating group, synthetic simplicity and gram-scale
production, which would enable the potential for economical production at
commercial scale in the future.
PMID- 26415987
TI - Mucus permeating nano-carrier systems.
PMID- 26415988
TI - Heart rate response to a caudal block in children anesthetized with sevoflurane
after ultrasound confirmation of placement.
AB - INTRODUCTION: Previous studies identified decreasing heart rate (HR) as a
predictor of successful caudal placement in children using halothane and
isoflurane. No changes were found in HR in the one study using sevoflurane. We
documented HR changes in children following a caudal block during sevoflurane
anesthesia utilizing ultrasound to confirm successful caudal placement. METHODS:
Seventy-one children (1-82 months) were anesthetized with sevoflurane. A caudal
block was placed with confirmation by ultrasound. Four aliquots of bupivacaine
0.2% with epinephrine 5 MUg . cc(-1) were administered for a total volume of 1 cc
. kg(-1) with HR recorded for 4 min. The outcomes measured were HR changes from
the initial baseline and during each 1-min interval. The age-related differences
in HR were also analyzed. RESULTS: Heart rate change from the initial baseline
after placing the caudal needle and allowing for equilibration ranged from -10.2%
to +8.9% and the HR change from the baseline at the start of each aliquot
injection ranged from -9.5% to +8.9%. Most participants (n = 60, 84.5%)
experienced at least one HR reduction over the observation period. For patients <
36 months, the HR change ranged from -11 to +12 b . min(-1) (mean -0.3); for
patients aged >= 36 months, the HR change ranged from -10 to +6 b . min(-1) (mean
-1.1). CONCLUSIONS: Heart rate changes following a caudal block in children <= 82
months of age anesthetized with sevoflurane is not a reliable indicator of a
successful block. Despite 100% caudal success, many children had no decrease in
HR, and in those that did, the decline was of a magnitude indeterminate from beat
to-beat variability.
PMID- 26415990
TI - Salvage computed tomography-guided transhepatic radiofrequency ablation for
unresected aldosteronoma of adrenohepatic fusion after adrenalectomy.
AB - Adrenalectomy is a treatment of choice for functioning adrenocortical adenoma. We
experienced a case of unresected aldosteronoma after right adrenalectomy.
Computed tomography-guided transhepatic radiofrequency ablation was carried out
to treat the unresected functioning adenoma. The purpose of our case report was
to show the clinical findings, computed tomography imaging features and computed
tomography-guided transhepatic ablation techniques for adrenocortical adenoma
arising from adrenohepatic fusion.
PMID- 26415989
TI - Radiofrequency ablation under 3D intraoperative Iso-C C-arm navigation for the
treatment of osteoid osteomas.
AB - OBJECTIVE: To evaluate the efficacy of intraoperative three-dimensional (3D) Iso
C C-arm-navigated percutaneous radiofrequency ablation (RFA) of osteoid osteomas.
METHODS: 35 patients (20 males and 15 females) with osteoid osteomas underwent
treatment with intraoperative 3D Iso-C C-arm navigation-guided RFA. The tumour
was first biopsied for pathological examination, the core needle was removed and
the RFA needle was inserted into the nidus. Post-operative X-rays and CT scans
were performed to evaluate the degree of ablation and to assess for recurrence at
3-month follow-up. Patients also completed a visual analogue scale (VAS) both pre
operatively and 3 days post-operatively to subjectively assess pain. RESULTS:
Pathological diagnosis confirmed osteoid osteoma in 19 cases. The other 16 cases
were not pathologically diagnosed owing to inadequate biopsy specimens. In all
cases, localized pain was immediately relieved following RFA. Patients reported
significantly decreased pain, with mean pre-operative VAS scores of 3.4 reducing
to 0.80 at 3 days post-operatively and further to 0.06 at 3-month follow-up (p <
0.05). The mean follow-up time was 15.5 months (range: 3-38 months). CONCLUSION:
3D Iso-C C-arm navigation-guided RFA is a safe and effective option for the
treatment of osteoid osteomas and may be considered in place of intraoperative CT
guided and open resection. ADVANCES IN KNOWLEDGE: C-arm image-guided percutaneous
RFA mitigates the need for pre-operative CT as well as intraoperative
scintigraphy, provides real-time imaging of the anatomy, facilitates accurate
resection of the tumour and enables immediate confirmation of excision.
PMID- 26415991
TI - The dynamic pattern of recurrence in curatively resected non-small cell lung
cancer patients: Experiences at a single institution.
AB - PURPOSE: To investigate the hazard function of tumor recurrence in patients with
completely (R0) resected non-small cell lung cancer. METHODS: A total of 1374
patients treated between 2003 and 2009 with complete resection and systematic
lymph node dissection were studied. The risk of recurrence at a given time after
operation was studied utilizing the cause-specific hazard function. Recurrence
was categorized as local recurrence or distant recurrence. The risk distribution
was assessed using clinical and pathological factors. RESULTS: The hazard
function for recurrence presented an early peak at approximately 10 months after
surgery and maintained a tapered plateau-like tail extending up to 8 years. A
similar risk pattern was detected for both local recurrence and distant
recurrence, while the risk of distant recurrence was higher than that of local
recurrence. The double-peaked pattern of hazard rate was present in several
subgroups, such as p-stage IA patients. A comparison of histology and status of
nodal involvement showed that pN1-2 adenocarcinoma patients demonstrated a high
hazard rate of distant recurrence and that pN0 adenocarcinoma patients exhibited
a small recurrent risk for a longer time. Squamous cell carcinoma patients showed
only little difference in risk. CONCLUSIONS: The data may be useful to select
patients at high risk of recurrence and may provide information for each patient
to decide how to manage the postoperative follow-up individually.
PMID- 26415992
TI - Anti-angiogenic-specific adverse events in patients with non-small cell lung
cancer treated with nintedanib and docetaxel.
AB - OBJECTIVES: LUME-Lung 1 was a randomized, placebo-controlled, Phase III trial
investigating nintedanib+docetaxel versus placebo+docetaxel in patients with
advanced NSCLC progressing after first-line chemotherapy. Progression-free
survival was significantly improved with nintedanib+docetaxel in the overall
population and overall survival was significantly improved in the pre-specified
analysis of patients with adenocarcinoma. We evaluated the frequency of
characteristic adverse events (AEs) commonly seen with existing anti-angiogenic
agents. MATERIALS AND METHODS: The incidence and intensity of AEs were evaluated
in all patients who received at least one dose of study medication (N=1307) and
for the two main histologies: adenocarcinoma (n=653) and squamous cell carcinoma
(SCC; n=553). AEs of special interest were analyzed by category, preferred term,
and worst CTCAE grade and included perforation, hypertension, bleeding,
thromboembolic events, and skin disorders. RESULTS AND CONCLUSION: The incidence
of patients with all-grade gastrointestinal (GI) perforations was low and
balanced between arms (0.5% in both) and across histologies; the incidence of non
GI perforations was 1.2% with nintedanib+docetaxel versus 0.2% with
placebo+docetaxel. The incidence of some events was higher with
nintedanib+docetaxel versus placebo+docetaxel; hypertension (3.5% vs 0.9%), rash
(11.0% vs 8.1%), and cutaneous adverse reactions (13.0% vs 10.7%). Rash and
cutaneous adverse reactions were predominantly Grade 1-2 with both treatments.
The incidence of all-grade bleeding was also slightly higher in
nintedanib+docetaxel-treated patients (14.1% vs 11.6%) driven by between
treatment differences in the SCC subpopulation; most events were Grade 1-2. The
proportion of patients with a thromboembolic event was low and comparable between
arms for all grades (5.1% vs 4.6%) and Grade >=3 (2.1% vs 3.1%). Safety
evaluation of the LUME-Lung 1 study showed that the frequency of AEs commonly
associated with other anti-angiogenic agents was lower with nintedanib+docetaxel.
Survival benefits from addition of nintedanib to docetaxel in patients with
adenocarcinoma after first-line therapy can be achieved alongside a manageable
safety profile.
PMID- 26415994
TI - Role of circulating-tumor DNA analysis in non-small cell lung cancer.
AB - The discovery of actionable driver mutations such as epidermal growth factor
receptor (EGFR) and microtubule-associated protein-like 4 anaplastic lymphoma
kinase (EML4-ALK) and their highly responses to EGFR and ALK tyrosine kinase
inhibitors (TKIs) in patients with advanced non-small-cell lung cancer (NSCLC)
allowed precise medicine into reality. However, a substantial part of patients
still have no sufficient tissue to perform genomic analysis. As a promising
noninvasive biomarker and potential surrogate for the entire tumor genome,
circulating tumor DNA (ctDNA) has been applied to the detection of driver gene
mutations and epigenetic alteration and monitoring of tumor burden, acquired
resistance, tumor heterogeneity and early diagnosis. Since precise therapy is a
strategy that optimal therapy is decided based on simultaneous tumor genome
information, ctDNA, as a liquid biopsy, may help to perform dynamic genetic
surveillance. In this paper we will perspectively discuss the biology and
identification of ctDNA in the blood of NSCLC patients and its clinical
applications in patient management.
PMID- 26415993
TI - Comparison of clinical outcome after first-line platinum-based chemotherapy in
different types of KRAS mutated advanced non-small-cell lung cancer.
AB - OBJECTIVES: As suggested by in-vitro data, we hypothesize that subtypes of KRAS
mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy
regimens. METHODS: Patients with advanced NSCLC and known KRAS mutation, treated
with first-line platinum-based chemotherapy, were retrieved from hospital
databases. PRIMARY OBJECTIVE: to investigate overall response rate (ORR),
progression free survival (PFS) and overall survival (OS) between different types
of platinum-based chemotherapy per type of KRAS mutation. RESULTS: 464 patients
from 17 hospitals, treated between 2000 and 2013, were included. The majority of
patients had stage IV disease (93%), had a history of smoking (98%) and known
with an adenocarcinoma (91%). Most common types of KRAS mutation were G12C (46%),
G12V (20%) and G12D (10%). Platinum was combined with pemetrexed (n=334), taxanes
(n=68) or gemcitabine (n=62). Patients treated with taxanes had a significant
improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; p<0.01).
Patients treated with bevacizumab in addition to taxanes (n=38) had the highest
ORR (62%). The PFS was significantly improved in patients treated with taxanes
compared to pemetrexed (HR=0.72, p=0.02), but not OS (HR=0.87, p=0.41). In
patients with G12V, significantly improved ORR (p<0.01) was observed for taxanes,
but not PFS or OS. Patients with G12C or G12D mutation had comparable ORR, PFS
and OS in all treatment groups. CONCLUSION: KRAS mutated NSCLC patients treated
with taxane-based chemotherapy had best ORR. Response to chemotherapy regimens
was different in types of KRAS mutation. Especially patients with G12V had better
response to taxane treatment.
PMID- 26415995
TI - Analysis of serum protein levels of angiogenic factors and their soluble
receptors as markers of response to cediranib in the NCIC CTG BR.24 clinical
trial.
AB - OBJECTIVES: Prognostic and predictive ability of circulating vascular endothelial
growth factor (VEGF), stromal derived factor (SDF)-1alpha and soluble VEGF
receptors (sVEGFR) 2 and 3, were evaluated in non-small cell lung cancer (NSCLC)
patients enrolled in NCIC Clinical Trials Group BR. 24 comparing chemotherapy
with or without cediranib. MATERIALS AND METHODS: Biomarker levels were assessed
by ELISA in serum from 149/296 enrolled patients at baseline and 146/149 patients
after one treatment cycle. Experimental cut-offs for baseline measures determined
using a graphic method were: VEGF-A: < or >=1 ng/ml, SDF-1alpha: <= or >3.5
ng/ml, sVEGFR2: < or >=11 ng/ml and sVEGFR3: < or >=35.5 ng/ml. Changes in
markers from baseline to on-treatment were predefined as increased >=10%, stable
within 10% or decreased >=10%. Cox regression models were used to correlate
biomarkers with patient characteristics and outcomes including progression-free
survival (PFS) and overall survival (OS). RESULTS: No baseline biomarker was
prognostic for OS, however, high baseline sVEGFR2 was prognostic for better PFS
(p=0.0008) in the chemotherapy alone arm. Low baseline sVEGFR2 or sVEGFR3 were
predictive of PFS benefit from cediranib (interaction p=0.06 and p=0.05,
respectively). While on treatment, VEGF-A increases were associated with better
PFS (p=0.02) and OS (p=0.01) for cediranib treated patients. Decreases in sVEGFR2
(p=0.01) or sVEGFR3 (p=0.02) were also predictive of better OS in cediranib
treated patients. CONCLUSIONS: Low baseline sVEGFR2 and sVEGFR3 were predictive
for PFS benefit from cediranib, whereas increases in VEGF-A and decreases in
sVEGFR2 or sVEGFR3 levels from baseline to on-treatment were predictive of an OS
benefit from cediranib in chemotherapy treated NSCLC patients. Validation of
these results is warranted.
PMID- 26415996
TI - The impact of respiratory gated positron emission tomography on clinical staging
and management of patients with lung cancer.
AB - OBJECTIVES: Respiratory motion artefacts during positron emission tomography
(PET) deteriorate image quality, potentially introducing diagnostic
uncertainties. The objective of this study was to determine the impact of optimal
respiratory gating on clinical staging and management of patients with primary
lung cancer. MATERIALS AND METHODS: From our fast-track outpatient diagnostic
program, 55 patients with primary lung cancer, who underwent whole body [(18)F]
fluorodeoxyglucose (FDG) PET, were included. Respiratory gating was performed on
bed positions covering the thorax and abdomen. Independent reading was conducted
by two nuclear medicine physicians. The observers scored the number and
anatomical location of the lesions, lymph node basins and the presence of distant
metastasis in non-gated and gated images. A tumor (T), lymph node (N), and
metastasis (M) stage was assigned to each patient according to the 7th revision
of the TNM classification. Staging accuracy was determined using
histopathological data and follow-up CT imaging. In addition, a management plan
was created for each patient based on non-gated and gated images by an
experienced pulmonologist. RESULTS: For nuclear medicine physician 1 and 2,
respiratory gating resulted in detection of more lesions in five and eight
patients (9% and 15%) respectively. However, this did not result in any migration
in T or M-stage. Migration in N-stage was observed in four and seven patients (7%
and 13%) for nuclear medicine physician 1 and 2 respectively. Staging accuracy
was slightly improved when respiratory gating was performed. Furthermore, there
was substantial agreement in patient management between non-gated and gated
images. CONCLUSIONS: Respiratory gating improved staging accuracy, mainly in
assessment of lymph node involvement. However, the effect on patient management
was limited due to the presence of already advanced disease stage in many
patients. These findings suggest that the expected impact of respiratory gating
will be solely on management of patients with early disease.
PMID- 26415997
TI - Neural networks of tinnitus in humans: Elucidating severity and habituation.
AB - The article reviews current data about the neural correlates of an individual's
reaction to tinnitus, primarily from studies that employ magnetic resonance
imaging (MRI). Human studies employing brain imaging remain the most commonly
used method to understand neural biomarkers of the reaction to tinnitus, a
subjective hearing disorder. Evidence from anatomical and functional MRI studies
is reviewed to better understand the large-scale neural networks implicated in
tinnitus habituation and severity. These networks are concerned with attention,
audition, and emotion, both during tasks and at 'rest' when no goal-directed
activity is expected. I place the data in the context of published literature and
current theories about tinnitus severity, while explaining the challenges and
limitations of human MRI studies. A possible model of habituation to tinnitus is
described, that of the attention system (via the frontal cortex) suppressing the
response from the amygdala and the use of alternate nodes of the limbic system
such as the insula and the parahippocampal gyrus when mediating emotion.
PMID- 26415999
TI - Dynamics of task-set carry-over: evidence from eye-movement analyses.
AB - Trial-to-trial carry-over of task sets (i.e., task-set inertia) is often
considered as a primary reason for task-switch costs. Yet, we know little about
the dynamics of such carry-over effects, in particular how much they are driven
by the most recent trial rather than characterized by a more continuous memory
gradient. Using eye-tracking, we examined in a 3-task, switching paradigm whether
there is a greater probability of non-target fixations to stimuli associated with
the previously relevant attentional set than to those associated with the less
recent set. Indeed, we found strong evidence for more interference (expressed in
terms of non-target fixations) from recent than from less-recent tasks and that
in particular the interference from pre-switch trials contributed substantially
to the overall pattern of response-time switch costs. Moreover, task-set carry
over was dominated by the most-recent trial when subjects could expect task
repetitions (with a 33 % switch rate). In comparison, when tasks were selected
randomly (with a 66 % switch rate), interference from the most recent trial
decreased, whereas interference from less-recent trials increased. In sum, carry
over interference dynamics were characterized both by a gradual recency gradient
and expectations about task-transition probabilities. Beyond that, there was
little evidence for a unique role of the most-recent trial.
PMID- 26415998
TI - Psychometric properties of the Tinnitus Functional Index (TFI): Assessment in a
UK research volunteer population.
AB - OBJECTIVES: Questionnaires are essential for measuring tinnitus severity and
intervention-related change but there is no standard instrument used routinely in
research settings. Most tinnitus questionnaires are optimised for measuring
severity but not change. However, the Tinnitus Functional Index (TFI) claims to
be optimised for both. It has not however been fully validated for research
purposes. Here we evaluate the relevant psychometric properties of the TFI,
specifically the questionnaire factor structure, reproducibility, validity and
responsiveness guided by quality criteria for the measurement properties of
health-related questionnaires. METHODS: The study involved a retrospective
analysis of data collected for 294 members of the general public who participated
in a randomised controlled trial of a novel tinnitus device (ClinicalTrials.gov
Identifier: NCT01541969). Participants completed up to eight commonly used
assessment questionnaires including the TFI, Tinnitus Handicap Inventory (THI),
Tinnitus Handicap Questionnaire (THQ), a Visual Analogue Scale of loudness (VAS
Loudness), Percentage Annoyance question, the Beck's Depression Inventory (BDI),
Beck's Anxiety Inventory (BAI), and the World Health Organisation Quality of Life
Bref (WHOQOL-BREF). A series of analyses assessed the study objectives. Forty
four participants completed the TFI at a second visit (within 7-21 days and
before receiving any intervention) providing data for reproducibility
assessments. RESULTS: The 8-factor structure was not fully confirmed for this
general (non-clinical) population. Whilst it was acceptable standalone subscale,
the 'auditory' factor showed poor loading with the higher order factor
'functional impact of tinnitus'. Reproducibility assessments for the overall TFI
indicate high internal consistency (alpha = 0.80) and extremely high reliability
(ICC: 0.91), whilst agreement was borderline acceptable (93%). Construct validity
was demonstrated by high correlations between scores on the TFI and THI (r =
0.82) and THQ (r = 0.82), moderate correlations with VAS-L (r = 0.46), PR-A (r =
0.58), BDI (r = 0.57), BAI (r = 0.39) and WHOQOL (r = -0.48). Floor effects were
observed for more than 50% of the items. A smallest detectable change score of
22.4 is proposed for the TFI global score. CONCLUSION: Even though the proposed 8
factor structure was not fully confirmed for this population, the TFI appears to
cover multiple symptom domains, and to measure the construct of tinnitus with an
excellent reliability in distinguishing between patients. While the TFI may
discriminate those whose tinnitus is not a problem, floor effects in many items
means it is less appropriate as a measure of change in this subgroup. Further
investigation is needed to determine whether these effects are relevant in other
populations.
PMID- 26416000
TI - Mind wandering during film comprehension: The role of prior knowledge and
situational interest.
AB - This study assessed the occurrence and factors that influence mind wandering (MW)
in the domain of film comprehension. The cascading model of inattention assumes
that a stronger mental representation (i.e., a situation model) during
comprehension results in less MW. Accordingly, a suppression hypothesis suggests
that MW would decrease as a function of having the knowledge of the plot of a
film prior to viewing, because the prior-knowledge would help to strengthen the
situation model during comprehension. Furthermore, an interest-moderation
hypothesis would predict that the suppression effect of prior-knowledge would
only emerge when there was interest in viewing the film. In the current
experiment, 108 participants either read a short story that depicted the plot
(i.e., prior-knowledge condition) or read an unrelated story of equal length
(control condition) prior to viewing the short film (32.5 minutes) entitled The
Red Balloon. Participants self-reported their interest in viewing the film
immediately before the film was presented. MW was tracked using a self-report
method targeting instances of MW with metacognitive awareness. Participants in
the prior-knowledge condition reported less MW compared with the control
condition, thereby supporting the suppression hypothesis. MW also decreased over
the duration of the film, but only for those with prior-knowledge of the film.
Finally, prior-knowledge effects on MW were only observed when interest was
average or high, but not when interest was low.
PMID- 26416001
TI - Role of personality and expectations for itch and scratching induced by
audiovisual itch stimuli.
AB - Itch is an unpleasant, bodily sensation, which--similar to pain--evokes
behavioral reactions. As a response to itch, people start scratching. There are
different ways to provoke itch and subsequent scratching in experimental
settings. A non-invasive method to induce itch and scratching is the presentation
of itch-related (audio-) visual stimulus material, like slide-supported lectures
on skin diseases or crawling insects. Also, watching videos showing other people
scratching provokes itch and the desire to scratch. In this review, we focus on
psychological factors, which were shown to be associated with itch and scratching
provoked by (audio-) visual itch stimuli. First, we summarize the findings on the
relationship between personality characteristics and (audio-) visually induced
itch. Agreeableness and self-consciousness were shown to be associated with
induced itch and scratching in patients with chronic skin diseases, while
neuroticism was linked to induced itch in healthy subjects. Second, we present
results of a recent study, in which we altered the expectations towards audio
visually induced itch and scratching by changing the information given on
upcoming itch stimuli. It was shown that subjects being informed about itch
stimuli in a neutral way displayed a shorter scratch duration in itch inducing
situations than subjects having catastrophizing expectations. Also, the increase
in scratch duration and in the number of scratch movements induced by audiovisual
itch stimuli was higher when the patients were not informed about itch induction.
Thus, in itch patients neither catastrophizing nor trivializing symptoms seems to
be helpful.
PMID- 26416002
TI - Effects of oral administration of trimethoprim-sulfamethoxazole on tear
production in clinically normal guinea pigs.
AB - OBJECTIVE: To determine the effects of short-term oral administration of
trimethoprim-sulfamethoxazole on tear production in clinically normal guinea
pigs. ANIMAL STUDIED: Thirty-two healthy adult Abyssinian guinea pigs were used
in this study. PROCEDURE: One day before the start of the trial, the pretreatment
baseline phenol red thread test (PRTT) values were recorded. Sixteen guinea pigs
in the treated group received 25 mg/kg trimethoprim-sulfamethoxazole orally twice
a day for 14 days. The other sixteen guinea pigs were used as untreated controls
and received a placebo during the study. All the ophthalmic tests were performed
without chemical restraint. PRTT values were evaluated in both eyes of all the
guinea pigs using a commercial PRTT strip of a single lot number on days 0
(baseline), 15, and 21 after starting the trial. RESULTS: The pretreatment
baseline mean +/- SD PRTT values for the treatment and control groups were 11.12
+/- 3.82 mm/15 s and 11.93 +/- 2.73 mm/15 s, respectively. After 14 days of drug
administration, the mean +/- SD PRTT values for the treatment and control groups
were 10.87 +/- 3.11 mm/15 s and 13.00 +/- 2.47 mm/15 s, respectively. On Day 21,
the mean +/- SD PRTT values for the treatment and control groups were 12.62 +/-
4.05 mm/15 s and 12.87 +/- 2.99 mm/15 s, respectively. Significant decreases in
the PRTT values, compared with the pretreatment baseline values, were not
observed in the treatment group on Day 15 (P = 0.14) and Day 21 (P = 0.31).
CONCLUSIONS: Trimethoprim-sulfamethoxazole did not decrease tear production in
the guinea pigs in this study.
PMID- 26416003
TI - Dyslipidaemia: Promising new therapy for lysosomal acid lipase deficiency.
PMID- 26416004
TI - Trastuzumab is not a tyrosine kinase inhibitor.
PMID- 26416005
TI - Mechanisms underlying trastuzumab activity are complex.
PMID- 26416007
TI - Statin Use and Serum Lipid Levels Are Associated With Survival Outcomes After
Surgery for Renal Cell Carcinoma.
AB - OBJECTIVE: To evaluate the association of statin use and preoperative serum lipid
parameters with oncologic outcomes following surgery for renal cell carcinoma.
METHODS: A total of 850 patients who underwent surgery for localized renal cell
carcinoma at our institution from 2000 to 2012 were included. Use of statins,
preoperative serum lipid profile, and comprehensive clinicopathologic features
were retrospectively recorded. Kaplan-Meier analysis and multivariate Cox
proportional hazards model were employed to compare survival outcomes. RESULTS:
There were 342 statin users and 508 non-users. Median follow-up was 25.0 months.
Statin users were older, had greater body mass index, and had worse performance
status than non-users. Tumor pathologic characteristics were balanced between
groups. Five-year recurrence free survival (RFS) was 77.9% for non-users compared
with 87.6% for statin users (P = .004). After adjustment for clinicopathologic
variables, statin use was independently associated with improved RFS (hazard
ratio [HR] 0.54, 95% confidence interval [CI] 0.33-0.86, P = .011) and overall
survival (HR 0.45, 95%CI 0.28-0.71, P = .001). In patients with available serum
lipid parameters (n = 193), 5-year RFS was 83.8% for patients with triglycerides
<250 mg/dL compared with 33.3% for those with triglycerides >250 mg/dL (P
<.0001). Elevated serum triglycerides (>250 mg/dL) was independently associated
with worse RFS (HR 2.69, 95%CI 1.22-5.93, P = .015) on multivariate analysis.
CONCLUSION: Statin use was independently associated with improved survival,
whereas elevated serum triglyceride levels correlated with worse oncologic
outcomes in this cohort. These findings warrant validation in prospective
studies.
PMID- 26416008
TI - Coffee, Tea, Cola, and Bladder Cancer Risk: Dose and Time Relationships.
AB - OBJECTIVE: To further analyze the relation between coffee, tea, and energy drinks
and bladder cancer risk, considering dose, duration, and other time-related
factors. METHODS AND RESULTS: A multicentric case-control study on 690 bladder
cancer cases and 665 hospital controls was conducted in Italy between 2003 and
2014. Odds ratios (ORs) for bladder cancer were estimated using multiple logistic
regression models. Sex-, age-, and tobacco-adjusted ORs were 1.27 (95% confidence
interval [CI] 0.84-1.94) for current drinkers and 1.69 (95% CI 1.05-2.72) for
lifetime drinkers of >=4 cups/day, compared with non- or occasional coffee
drinkers. The corresponding ORs for an increment of 1 cup/day were 1.03 (95% CI
0.96-1.11) and 1.07 (95% CI 0.99-1.15). No association was found between bladder
cancer risk and duration or age at starting, and no significant heterogeneity was
found according to age and sex, although a slight increased risk emerged in never
smokers. Decaffeinated coffee, tea, cola, and energy drinks were not related with
bladder cancer risk. CONCLUSION: Our study found no significant relation between
coffee and bladder cancer risk after accounting for smoking, although the OR was
above unity for high lifetime habit. The lack of dose and duration relationships,
however, suggests the absence of a causal relation.
PMID- 26416009
TI - Unsuccessful Medical Expulsive Therapy: A Cost to Waiting?
AB - OBJECTIVE: To compare clinical outcomes between patients with ureteral stones who
underwent an unsuccessful trial of medical expulsive therapy (MET) and patients
who did not attempt MET. METHODS: We reviewed the clinical records of all
potential candidates for MET who were referred from the emergency department to a
subspecialty stone clinic. RESULTS: Of 348 potential candidates, 133 patients
(38%) went directly to surgery (NMET) and 215 patients (62%) initiated MET. In
the latter group, MET was unsuccessful in 45 patients (21%) (UMET). Stone
symptoms were the primary rationale for surgery in 20 (44%) UMET patients and 69
(52%) NMET patients. The UMET patients were more likely to be younger and have
smaller, more distal stones than NMET patients. All stones were cleared by
ureteroscopy. The average interval from stone clinic assessment to surgery was
longer in the UMET patients (17 days) than in the NMET patients (1 day; P <.001).
The UMET patients underwent more preoperative computed-tomography scans (2.1)
than did the NMET patients (1; P <0.001). There were no differences between the 2
groups in the residual stone burden, pre- or postoperative repeat visits to the
emergency department, or repeat surgery. CONCLUSION: In this population, we did
not observe any detrimental impact of an unsuccessful trial of MET (beyond the
additional time and imaging costs). If more confident and effective symptom
control could be achieved, expansion of utilization and duration of MET may be a
path to improved patient outcomes and cost control.
PMID- 26416010
TI - Linking transcriptomics and proteomics in spermatogenesis.
AB - Spermatogenesis is a complex and tightly regulated process leading to the
continuous production of male gametes, the spermatozoa. This developmental
process requires the sequential and coordinated expression of thousands of genes,
including many that are testis-specific. The molecular networks underlying normal
and pathological spermatogenesis have been widely investigated in recent decades,
and many high-throughput expression studies have studied genes and proteins
involved in male fertility. In this review, we focus on studies that have
attempted to correlate transcription and translation during spermatogenesis by
comparing the testicular transcriptome and proteome. We also discuss the recent
development and use of new transcriptomic approaches that provide a better proxy
for the proteome, from both qualitative and quantitative perspectives. Finally,
we provide illustrations of how testis-derived transcriptomic and proteomic data
can be integrated to address new questions and how the 'proteomics informed by
transcriptomics' technique, by combining RNA-seq and MS-based proteomics, can
contribute significantly to the discovery of new protein-coding genes or new
protein isoforms expressed during spermatogenesis.
PMID- 26416006
TI - New medical therapies for heart failure.
AB - Heart failure (HF) can rightfully be called the epidemic of the 21(st) century.
Historically, the only available medical treatment options for HF have been
diuretics and digoxin, but the capacity of these agents to alter outcomes has
been brought into question by the scrutiny of modern clinical trials. In the past
4 decades, neurohormonal blockers have been introduced into clinical practice,
leading to marked reductions in morbidity and mortality in chronic HF with
reduced left ventricular ejection fraction (LVEF). Despite these major advances
in pharmacotherapy, our understanding of the underlying disease mechanisms of HF
from epidemiological, clinical, pathophysiological, molecular, and genetic
standpoints remains incomplete. This knowledge gap is particularly evident with
respect to acute decompensated HF and HF with normal (preserved) LVEF. For these
clinical phenotypes, no drug has been shown to reduce long-term clinical event
rates substantially. Ongoing developments in the pharmacotherapy of HF are likely
to challenge our current best-practice algorithms. Novel agents for HF therapy
include dual-acting neurohormonal modulators, contractility-enhancing agents,
vasoactive and anti-inflammatory peptides, and myocardial protectants. These
novel compounds have the potential to enhance our armamentarium of HF
therapeutics.
PMID- 26416012
TI - Junior doctors to be balloted on industrial action.
PMID- 26416011
TI - Integrative analyses reveal transcriptome-proteome correlation in biological
pathways and secondary metabolism clusters in A. flavus in response to
temperature.
AB - To investigate the changes in transcript and relative protein levels in response
to temperature, complementary transcriptomic and proteomic analyses were used to
identify changes in Aspergillus flavus grown at 28 degrees C and 37 degrees C.
A total of 3,886 proteins were identified, and 2,832 proteins were reliably
quantified. A subset of 664 proteins was differentially expressed upon
temperature changes and enriched in several Kyoto Encyclopedia of Genes and
Genomes pathways: translation-related pathways, metabolic pathways, and
biosynthesis of secondary metabolites. The changes in protein profiles showed low
congruency with alterations in corresponding transcript levels, indicating that
post-transcriptional processes play a critical role in regulating the protein
level in A. flavus. The expression pattern of proteins and transcripts related to
aflatoxin biosynthesis showed that most genes were up-regulated at both the
protein and transcript level at 28 degrees C. Our data provide comprehensive
quantitative proteome data of A. flavus at conducive and nonconducive
temperatures.
PMID- 26416013
TI - SOAP-V: Introducing a method to empower medical students to be change agents in
bending the cost curve.
AB - Medical students must learn how to practice high-value, cost-conscious care. By
modifying the traditional SOAP (Subjective-Objective-Assessment-Plan)
presentation to include a discussion of value (SOAP-V), we developed a cognitive
forcing function designed to promote discussion of high-value, cost-conscious
care during patient delivery. The SOAP-V model prompts the student to consider
(1) the evidence that supports a test or treatment, (2) the patient's preferences
and values, and (3) the financial cost of a test or treatment compared to
alternatives. Students report their findings to their teams during patient care
rounds. This tool has been successfully used at 3 medical schools. Preliminary
results find that students who have been trained in SOAP-V feel more empowered to
address the economic healthcare crisis, are more comfortable in initiating
discussions about value, and are more likely to consider potential costs to the
healthcare system.
PMID- 26416014
TI - A new nanocomposite forward osmosis membrane custom-designed for treating shale
gas wastewater.
AB - Managing the wastewater discharged from oil and shale gas fields is a big
challenge, because this kind of wastewater is normally polluted by high contents
of both oils and salts. Conventional pressure-driven membranes experience little
success for treating this wastewater because of either severe membrane fouling or
incapability of desalination. In this study, we designed a new nanocomposite
forward osmosis (FO) membrane for accomplishing simultaneous oil/water separation
and desalination. This nanocomposite FO membrane is composed of an oil-repelling
and salt-rejecting hydrogel selective layer on top of a graphene oxide (GO)
nanosheets infused polymeric support layer. The hydrogel selective layer
demonstrates strong underwater oleophobicity that leads to superior anti-fouling
capability under various oil/water emulsions, and the infused GO in support layer
can significantly mitigate internal concentration polarization (ICP) through
reducing FO membrane structural parameter by as much as 20%. Compared with
commercial FO membrane, this new FO membrane demonstrates more than three times
higher water flux, higher removals for oil and salts (>99.9% for oil and >99.7%
for multivalent ions) and significantly lower fouling tendency when investigated
with simulated shale gas wastewater. These combined merits will endorse this new
FO membrane with wide applications in treating highly saline and oily
wastewaters.
PMID- 26416015
TI - Adherence to surgical hand rubbing directives in a hospital district of Southwest
Finland.
AB - BACKGROUND: The primary objective was to measure the compliance with alcohol
based surgical hand rubbing (SHR) among operation room personnel. The secondary
objective was to evaluate the effect of feedback sessions on compliance. METHODS:
This was a prospective observational before-after intervention study. Between
October 2010 and June 2012 the hygiene nurses observed SHR among operation room
personnel in the hospital district of Southwest Finland. After feedback sessions
a second observation round was conducted in the main operation room of Turku
University Hospital. The first observation round comprised 477 observations: 259
(54%) were doctors, 190 (40%) nurses and 28 (5%) other personnel. In the second
observation round a total of 210 observations were made. RESULTS: During the
first round in 42% of observations the 3 min SHR time recommended by WHO was
used. Median times for SHR were 1 min 50 s (range 0 min to 5 min 44 s) for
doctors and 3 min 25 s (range 1 min 1 s to 8 min 15 s) for nurses, respectively
(p < 0.0001). In 40% of observations hands were not properly dried after a wash
before applying SHR and in 45% hands were not allowed to dry properly after SHR
before donning surgical gloves. After feedback, time for SHR did not
significantly improve but technique did. CONCLUSIONS: SHR was performed
incorrectly in most observations even after feedback. The results stress the
importance of more effective education, helping techniques and positive role
models for operation room personnel to promote SHR.
PMID- 26416016
TI - Predictors of condom use behaviour among male street labourers in urban Vietnam
using a modified Information-Motivation-Behavioral Skills (IMB) model.
AB - HIV risk in vulnerable groups such as itinerant male street labourers is often
examined via a focus on individual determinants. This study provides a test of a
modified Information-Motivation-Behavioral Skills (IMB) model to predict condom
use behaviour among male street workers in urban Vietnam. In a cross-sectional
survey using a social mapping technique, 450 male street labourers from 13
districts of Hanoi, Vietnam were recruited and interviewed. Collected data were
first examined for completeness; structural equation modelling was then employed
to test the model fit. Condoms were used inconsistently by many of these men, and
usage varied in relation to a number of factors. A modified IMB model had a
better fit than the original IMB model in predicting condom use behaviour. This
modified model accounted for 49% of the variance, versus 10% by the original
version. In the modified model, the influence of psychosocial factors was
moderately high, whilst the influence of HIV prevention information, motivation
and perceived behavioural skills was moderately low, explaining in part the
limited level of condom use behaviour. This study provides insights into social
factors that should be taken into account in public health planning to promote
safer sexual behaviour among Asian male street labourers.
PMID- 26416017
TI - Reward breaks through center-surround inhibition via anterior insula.
AB - Focusing attention on a target creates a center-surround inhibition such that
distractors located close to the target do not capture attention. Recent research
showed that a distractor can break through this surround inhibition when
associated with reward. However, the brain basis for this reward-based attention
is unclear. In this fMRI study, we presented a distractor associated with high or
low reward at different distances from the target. Behaviorally the low-reward
distractor did not capture attention and thus did not cause interference, whereas
the high-reward distractor captured attention only when located near the target.
Neural activity in extrastriate cortex mirrored the behavioral pattern. A
comparison between the high-reward and the low-reward distractors presented near
the target (i.e., reward-based attention) and a comparison between the high
reward distractors located near and far from the target (i.e., spatial attention)
revealed a common frontoparietal network, including inferior frontal gyrus and
inferior parietal sulcus as well as the visual cortex. Reward-based attention
specifically activated the anterior insula (AI). Dynamic causal modelling showed
that reward modulated the connectivity from AI to the frontoparietal network but
not the connectivity from the frontoparietal network to the visual cortex. Across
participants, the reward-based attentional effect could be predicted both by the
activity in AI and by the changes of spontaneous functional connectivity between
AI and ventral striatum before and after reward association. These results
suggest that AI encodes reward-based salience and projects it to the stimulus
driven attentional network, which enables the reward-associated distractor to
break through the surround inhibition in the visual cortex.
PMID- 26416018
TI - Simultaneous enantioselective determination of triadimefon and its metabolite
triadimenol in edible vegetable oil by gel permeation chromatography and
ultraperformance convergence chromatography/tandem mass spectrometry.
AB - A novel, sensitive, and efficient enantioselective method for the determination
of triadimefon and its metabolite triadimenol in edible vegetable oil, was
developed by gel permeation chromatography and ultraperformance convergence
chromatography/tandem triple quadrupole mass spectrometry. After the vegetable
oil samples were prepared using gel permeation chromatography, the eluent was
collected, evaporated, and dried with nitrogen gas. The residue was redissolved
by adding methanol up to a final volume of 1 mL. The analytes of six enantiomers
were analyzed on Chiralpak IA-3 column (150 * 4.6 mm) using compressed liquid CO2
mixed 14 % co-solvents, comprising methanol/acetonitrile/isopropanol = 20/20/60
(v/v/v) in the mobile phase at 30 degrees C, and the total separation time was
less than 4 min at a flow rate of 2 mL/min. Quantification was achieved using
matrix-matched standard calibration curves. The overall mean recoveries for six
enantiomers from vegetable oil were 90.1-97.3 %, with relative standard
deviations of 0.8-5.4 % intra-day and 2.3-5.0 % inter-day at 0.5, 5, and 50
MUg/kg levels. The limits of quantification were 0.5 MUg/kg for all enantiomers
based on five replicate extractions at the lowest fortified level in vegetable
oil. Moreover, the absolute configuration of six enantiomers had been determined
based on comparisons of the vibrational circular dichroism experimental spectra
with the theoretical curve obtained by density functional theory calculations.
Application of the proposed method to the 40 authentic vegetable oil samples from
local markets suggests its potential use in enantioselective determination of
triadimefon and triadimenol enantiomers. Graphical Abstract Chemical structures
and UPC(2)-MS/MS separation chromatograms of triadimefon and triadimenol.
PMID- 26416020
TI - Characterisation of a fibre optic Raman probe within a hypodermic needle.
AB - We demonstrate the first use of a multifibre Raman probe that fits inside the
bore of a hypodermic needle. A Raman probe containing multiple collection fibres
provides improved signal collection efficiency in biological samples compared
with a previous two-fibre design. Furthermore, probe performance (signal-to-noise
ratios) compared favourably with the performance achieved in previous Raman
microscope experiments able to distinguish between benign lymph nodes, primary
malignancies in lymph nodes and secondary malignancies in lymph nodes. The
experimental measurements presented here give an indication of the sampling
volume of the Raman needle probe in lymphoid tissues. Liquid tissue phantoms were
used that contained scattering medium encompassing a range of scattering
properties similar to those of a variety of tissue types, including lymph node
tissues. To validate the appropriateness of the phantoms, the sampling depth of
the probe was also measured in excised lymph node tissue. More than 50 % of Raman
photons collected were found to originate from between the tip of the needle and
a depth of 500 MUm into the tissue. The needle probe presented here achieves
spectral quality comparable to that in numerous studies previously demonstrating
Raman disease discrimination. It is expected that this approach could achieve
targeted subcutaneous tissue measurements and be viable for use for the in vivo
Raman diagnostics of solid organs located within a few centimetres below the
skin's surface. Graphical Abstract Schematic of multi-fibre Raman needle probe
with disposible tips and proximal optical filtration.
PMID- 26416019
TI - Design of a sensitive fluorescent polarization immunoassay for rapid screening of
milk for cephalexin.
AB - In this paper we describe the development of a sensitive, fast, and easily
performed fluorescence polarization immunoassay for determination of cephalexin
in milk. The experimental work was performed to increase sensitivity and
specificity. Therefore, the structures of the tracers were varied by synthesis of
both cephalexin (CEX) and cephalotin (CET) conjugates with a variety of
fluorescent labels. Two rabbit antisera containing antibodies against cephalexin
and cephalotin were tested in homologous and heterologous combinations with the
tracers. For every working antibody-tracer combination, the analytical conditions
and cross-reactivity for structural analogues-cephalosporins and other
antibiotics that could also be present in milk-were determined. It was found that
the highest sensitivity was achieved by use of the homologous pair CET-EDF-anti
CET antibody (limit of detection (LOD) 0.4 MUg kg(-1) for standard solutions
prepared in buffer), but this combination was not appropriate because of high
cross-reactivity with CET. For subsequent experiments, therefore, CEX- EDF-anti
CEX antibody were chosen (LOD 0.8 MUg kg(-1) for standard solutions prepared in
buffer). Part of this manuscript is devoted to the variation of precipitation
agents for pretreatment of milk before analysis; milk is an extremely complicated
matrix. The optimum protein precipitation agent was methanol. This technique for
cephalexin determination was characterized by a limit of detection of 1 MUg kg(
1). The method was validated by using naturally contaminated and spiked milk
samples. The results obtained corresponded very well with those obtained by HPLC,
which was used as confirmation method.
PMID- 26416021
TI - Pharmacokinetic study of Gastrodia elata in rats.
AB - The pharmacokinetics of parishin, gastrodin, Gastrodia elata extract and Rhizoma
Gastrodiae capsule was investigated by intragastric and/or intravenous
administration to rats. Parishin was metabolized into nine metabolites after
intravenous administration, and the area under the curve (AUC0-infinity) of
parishin and its metabolites (except parishin G and parishin E) increased
nonlinearly from 72.5 to 220 mg/kg. When combining regression equation with the
AUC0-infinity and dose of gastrodin injection, the percent conversion of parishin
to gastrodin was obtained as 50 %. Based on multi-active metabolites of parishin
in vivo, integrated pharmacokinetic mode was established. It is notable that each
metabolite from parishin shares the similar metabolic process at three dosages of
parishin and the bioavailability of parishin was approximately 14 %. The
integrated pharmacokinetic mode was successfully applied to evaluate the holistic
pharmacokinetics of gastrodin injection, G. elata extract and Rhizoma Gastrodiae
capsule. The results showed that the holistic pharmacokinetics of gastrodin
injection and G. elata extract was closed to that of gastrodin, but for parishin
and Rhizoma Gastrodiae capsule, integrated pharmacokinetic parameters were more
suitable to evaluate its holistic pharmacokinetics. Graphical abstract
Pharmacokinetic study of Gastrodia elata in rats.
PMID- 26416022
TI - Screening of pharmaceuticals and illicit drugs in wastewater and surface waters
of Spain and Italy by high resolution mass spectrometry using UHPLC-QTOF MS and
LC-LTQ-Orbitrap MS.
AB - The existence of pharmaceuticals and illicit drugs (PIDs) in environmental waters
has led many analytical chemists to develop screening methods for monitoring
purposes. Water samples can contain a huge number of possible contaminants,
commonly at low concentrations, which makes their detection and identification
problematic. Liquid chromatography coupled with high resolution mass spectrometry
(LC-HRMS) has proven itself effective in the screening of environmental
contaminants. The present work investigates the use of the most popular HRMS
instruments, quadrupole time-of-flight and linear trap quadrupole-Orbitrap, from
two different laboratories. A suspect screening for PIDs was carried out on
wastewater (influent and effluent) and surface water samples from Castellon,
Eastern Spain, and Cremona, Northern Italy, incorporating a database of 107 PIDs
(including 220 fragment ions). A comparison between the findings of both
instruments and of the samples was made which highlights the advantages and
drawbacks of the strategies applied in each case. In total, 28 compounds were
detected and/or identified by either/both instruments with irbesartan, valsartan,
benzoylecgonine and caffeine being the most commonly found compounds across all
samples.
PMID- 26416023
TI - Differential Plasma-cell evolution is linked with Dermatophagoides pteronyssinus
immunotherapy response.
AB - Allergic rhinitis is highly prevalent worldwide. Immunotherapy has been shown to
control its symptoms, however, up to 30% of patients may not respond. Previous
studies of the immunological mechanisms involved in allergen-immunotherapy (AIT)
have focused on the humoral and T-cell response and several studies have
evaluated some B-cell subpopulations during AIT and their role in immunological
tolerance. However, although B and plasma-cell subpopulations are two of the most
important cellular subtypes involved in allergic reactions, their relation with
AIT efficacy remains unelucidated. The objective was to analyze the effects of
immunotherapy on different B and plasma-cell subpopulations and whether these
changes correlate with the clinical response to the treatment. Although no
changes are found in B-cell subpopulations, responder patients show increased
levels of memory B-cells even before the beginning of treatment. Changes in
plasma-cell subpopulations are found, mainly in circulating inflammatory plasma
cells that could affect the response to the allergen. Moreover, an early increase
of specific-IgG4 and IgG4 secreting-cells was found. All these suggest that the
determination of the memory B-cells before the initiation of the treatment, and
the quantification of IgG4 and IgG4-secreting-cells in the first months of
immunotherapy, could serve as markers for the clinical response to treatment.
PMID- 26416024
TI - Increased duplex stabilization in porphyrin-LNA zipper arrays with structure
dependent exciton coupling.
AB - Porphyrins were attached to LNA uridine building blocks via rigid 5-acetylene or
more flexible propargyl-amide linkers and incorporated into DNA strands. The
systems show a greatly increased thermodynamic stability when using as little as
three porphyrins in a zipper arrangement. Thermodynamic analysis reveals
clustering of the strands into more ordered duplexes with both greater negative
DeltaDeltaS and DeltaDeltaH values, and less ordered duplexes with small positive
DeltaDeltaS differences, depending on the combination of linkers used. The
exciton coupling between the porphyrins is dependent on the flanking DNA sequence
in the single stranded form, and on the nature of the linker between the
nucleobase and the porphyrin in the double stranded form; it is, however, also
strongly influenced by intermolecular interactions. This system is suitable for
the formation of stable helical chromophore arrays with sequence and structure
dependent exciton coupling.
PMID- 26416025
TI - Physical therapy vs. internet-based exercise training (PATH-IN) for patients with
knee osteoarthritis: study protocol of a randomized controlled trial.
AB - BACKGROUND: Physical activity improves pain and function among individuals with
knee osteoarthritis (OA), but most people with this condition are inactive.
Physical therapists play a key role in helping people with knee OA to increase
appropriate physical activity. However, health care access issues, financial
constraints, and other factors impede some patients from receiving physical
therapy (PT) for knee OA. A need exists to develop and evaluate other methods to
provide physical activity instruction and support to people with knee OA. This
study is examining the effectiveness of an internet-based exercise training
(IBET) program designed for knee OA, designed by physical therapists and other
clinicians. METHODS/DESIGN: This is a randomized controlled trial of 350
participants with symptomatic knee OA, allocated to three groups: IBET, standard
PT, and a wait list (WL) control group (in a 2:2:1 ratio, respectively). The
study was funded by the Patient Centered Outcomes Research Institute, which
conducted a peer review of the proposal. The IBET program provides patients with
a tailored exercise program (based on functional level, symptoms, and current
activity), video demonstrations of exercises, and guidance for appropriate
exercise progression. The PT group receives up to 8 individual visits with a
physical therapist, mirroring standard practice for knee OA and with an emphasis
on a home exercise program. Outcomes are assessed at baseline, 4 months (primary
time point) and 12 months (to assess maintenance of treatment effects). The
primary outcome is the Western Ontario and McMaster Universities Osteoarthritis
Index, and secondary outcomes include objective physical function, satisfaction
with physical function, physical activity, depressive symptoms and global
assessment of change. Linear mixed models will be used to compare both the IBET
and standard PT groups to the WL control group, examine whether IBET is non
inferior to PT (a treatment that has an established evidence base for knee OA),
and explore whether participant characteristics are associated with differential
effects of IBET and/or standard PT. This research is in compliance with the
Helsinki Declaration and was approved by the Institutional Review Board of the
University of North Carolina at Chapel Hill. DISCUSSION: The IBET program could
be disseminated widely at relatively low cost and could be an important resource
for helping patients with knee OA to adopt and maintain appropriate physical
activity. This trial will provide an important evaluation of the effectiveness of
this IBET program for knee OA. TRIAL REGISTRATION: NCT02312713.
PMID- 26416026
TI - Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of
microcephalic primordial dwarfism.
AB - BACKGROUND: Primordial dwarfism is a state of extreme prenatal and postnatal
growth deficiency, and is characterized by marked clinical and genetic
heterogeneity. RESULTS: Two presumably unrelated consanguineous families
presented with an apparently novel form of primordial dwarfism in which severe
growth deficiency is accompanied by distinct facial dysmorphism, brain
malformation (microcephaly, agenesis of corpus callosum, and simplified
gyration), and severe encephalopathy with seizures. Combined autozygome/exome
analysis revealed a novel missense mutation in WDR4 as the likely causal variant.
WDR4 is the human ortholog of the yeast Trm82, an essential component of the
Trm8/Trm82 holoenzyme that effects a highly conserved and specific (m(7)G46)
methylation of tRNA. The human mutation and the corresponding yeast mutation
result in a significant reduction of m(7)G46 methylation of specific tRNA
species, which provides a potential mechanism for primordial dwarfism associated
with this lesion, since reduced m(7)G46 modification causes a growth deficiency
phenotype in yeast. CONCLUSION: Our study expands the number of biological
pathways underlying primordial dwarfism and adds to a growing list of human
diseases linked to abnormal tRNA modification.
PMID- 26416028
TI - Staphylococcus aureus food poisoning among Bulawayo City Council employees,
Zimbabwe, 2014.
AB - BACKGROUND: Bulawayo City Council held an Integrated Result Based Management
workshop among 86 employees from August 18-22, 2014 at Ikhwezi Training Centre in
Bulawayo City. On August 21, 2014, a report of diarrhoea among Council employees
attending the workshop was received. We investigated the outbreak to determine
the risk factors associated with diarrhoea at Ikhwezi Training Centre, Bulawayo
City. METHOD: A retrospective cohort study was conducted where 74 Council
employees were interviewed on food consumed and presenting signs and symptoms.
Stool specimens and hand swabs were collected for culture. Water samples were
collected for bacteriological analysis. Food samples were not available. Data
were analysed using Epi InfoTM to generate frequencies, means, proportions, risk
ratios, and attributable risk. RESULTS: Of the 74 employees interviewed 34
(45.9%) were males and 40 (54%) were females. The response rate was 94%. The
common signs and symptoms included abdominal cramps (88.7%), and watery diarrhoea
(86.8%). The overall attack rate was 71.6%. Eating stewed chicken (RR = 2.52, 95%
CI 1.30-4.89) served at hour 13:00 during lunch on August 20, 2014 at Ikhwezi
Training Centre was the only significant risk factor associated with food
poisoning. Drinking purified bottled water [RR = 0.67, 95% CI (0.57-0.79)] was
found to be protective. Staphylococcus aureus was isolated from the hands and
nails of food handlers. CONCLUSION: The outbreak was due to food poisoning and
was most likely caused by the Staphylococcus aureus formed toxins. Stewed chicken
served during lunch on August 20, 2014 was the possible source of infection.
Contamination might have occurred during food handling and preparation. Training
of food handlers in basic food hygiene and safety is recommended.
PMID- 26416027
TI - Social and economic costs and health-related quality of life in non
institutionalised patients with cystic fibrosis in the United Kingdom.
AB - BACKGROUND: This study aimed to determine the societal economic burden and health
related quality of life (HRQOL) of cystic fibrosis (CF) patients in the UK.
METHODS: A bottom-up cost-of-illness, cross-sectional, retrospective analysis of
74 patients was conducted aiming to estimate the economic impact of CF. Data on
demographic characteristics, health resource utilisation, informal care,
productivity losses and HRQOL were collected from questionnaires completed by
patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ
5D) instrument. RESULTS: Using unit costs for 2012 we found that the average
annual cost for a CF patient was ?48,603, with direct health care costs amounting
to ?20,854 (42.9 % of total costs), direct non-health care costs being ?21,528
(44.3 %) and indirect costs attributable to productivity losses being ?6,222
(12.8 %). On average, the largest expenditures by far were accounted for by
informal care (44.1 %), followed by medications (14.5 %), acute hospitalisations
(13.9 %), early retirement (9.1 %) and outpatient and primary health care visits
(7.9 %). Sharp differences existed depending on whether CF patients were in need
of caregiver help (?76,271 versus ?26,335). In adult CF patients, mean EQ-5D
index scores were 0.64 (0.93 in the general population) and mean EQ-5D visual
analogue scale scores were 62.23 (86.84 in the general population); among
caregivers, these scores were 0.836 and 80.85, respectively. DISCUSSION: Our
analysis highlights the importance of the economic and quality of life
consequences of CF from a societal perspective. The results highlight that beyond
conventional costs such as acute hospitalisations, medication and outpatient and
primary care visits, indirect costs related to informal care and early
retirement, have significant societal implications. Similarly, our analysis
showed that the average EQ-5D index score of adult CF patients was significantly
lower than in the general population, an indication that a methodological bias
may exist in using the latter in economic analyses. CONCLUSION: CF poses a
significant cost burden on UK society, with non-health care and indirect costs
representing 57 % of total average costs, and HRQOL being considerably lower than
in the general population.
PMID- 26416031
TI - When patients and surgeons disagree about surgical outcome: investigating patient
factors and chart note communication.
AB - OBJECTIVE: Effective physician-patient communication is a critical component of a
clinical practice and in order to achieve optimal patient outcomes. We aimed to
investigate indirect effects of physician-patient communication by examining the
relationship between a physician-patient mismatch in perceived outcomes and
content in the medical record's clinical note. We compared patient records whose
perceived subjective assessment of surgery outcomes agreed or disagreed with the
surgeon's perception of that outcome (Subjective Disagreement). METHODS: This
study included 172 spine surgery patients at a teaching hospital. Patient
reported outcomes included the Oswestry Disability Index; the Short-Form 36; and
a Visual Analogue Scale items for leg and back pain. We content-analyzed the
clinical note in the medical record, and used logistic regression to evaluate
predictors of Subjective Disagreement (n = 41 disagreed vs. 131 agreed). RESULTS:
Patient and surgeon agreed in 76% of cases and disagreed in 24% of cases.
Patients who assessed their outcome worse than their surgeons tended to be less
educated and involved in litigation. They also tended to report worsened mental
health and leg pain. Content analysis revealed group differences in surgeon
communication patterns in the chart notes related to how symptom change was
emphasized, how follow-up was described, and a specific word reference.
Specifically, disagreement was predicted by using "much" to emphasize the
findings and noting long-term prognosis. Agreement was predicted by use of
positive emphasis terms, having an "as-needed" follow-up plan, and using "happy"
in the chart note. CONCLUSION: The nature of measuring outcomes of surgery is
based on patient perception. In surgeon-patient perspective mismatches, patient
factors may serve as barriers to improvement. Worsened change on patient-reported
mental health may be an independent factor which colors the patient's general
perceptions. This aspect of treatment may be missed by the spine surgeon. Chart
note communication styles reflect the subjective disagreement. Investigating and/
or treating mental health deterioration may be valuable in resolving this
mismatch and for overall outcome.
PMID- 26416029
TI - Protocol for a statewide randomized controlled trial to compare three training
models for implementing an evidence-based treatment.
AB - BACKGROUND: Evidence-based treatments (EBTs) are available for treating childhood
behavioral health challenges. Despite EBTs' potential to help children and
families, they have primarily remained in university settings. Little empirical
evidence exists regarding how specific, commonly used training and quality
control models are effective in changing practice, achieving full implementation,
and supporting positive client outcomes. METHODS/DESIGN: This study (NIMH RO1
MH095750; ClinicalTrials.gov Identifier: NCT02543359), which is currently in
progress, will evaluate the effectiveness of three training models (Learning
Collaborative (LC), Cascading Model (CM), and Distance Education (DE)) to
implement a well-established EBT , Parent-Child Interaction Therapy, in real
world, community settings. The three models differ in their costs, skill
training, quality control methods, and capacity to address broader implementation
challenges. The project is guided by three specific aims: (1) to build knowledge
about training outcomes, (2) to build knowledge about implementation outcomes,
and (3) to test the differential impact of training clinicians using LC, CM, and
DE models on key client outcomes. Fifty (50) licensed psychiatric clinics across
Pennsylvania were randomized to one of the three training conditions: (1) LC, (2)
CM, or (3) DE. The impact of training on practice skills (clinician level) and
implementation/sustainment outcomes (clinic level) are being evaluated at four
timepoints coinciding with the training schedule: baseline, 6 (mid), 12 (post),
and 24 months (1 year follow-up). Immediately after training begins, parent-child
dyads (client level) are recruited from the caseloads of participating
clinicians. Client outcomes are being assessed at four timepoints (pre-treatment,
1, 6, and 12 months after the pre-treatment). DISCUSSION: This proposal builds on
an ongoing initiative to implement an EBT statewide. A team of diverse
stakeholders including state policy makers, payers, consumers, service providers,
and academics from different, but complementary areas (e.g., public health,
social work, psychiatry), has been assembled to guide the research plan by
incorporating input from multidimensional perspective. TRIAL REGISTRATION:
ClinicalTrials.gov: NCT02543359.
PMID- 26416030
TI - Are work return and leaves of absence predictable after an unstable pelvic ring
injury?
AB - BACKGROUND: Resuming work after surgical treatment of an unstable pelvic ring
injury is often impeded because of residual disability. The aim of this study was
to test which factors influence return to work, ability to return to the same job
function as before the injury, leaves of absence, and incapacitation after
sustaining a pelvic fracture. MATERIALS AND METHODS: We performed a retrospective
study on patients with surgically treated pelvic fractures. Medical records were
reviewed to document patients' demographic data, the extent of follow-up care,
diagnosis of the injury (according to the Tile system of classification), type of
surgical treatment, injury severity, and the time from trauma to definitive
surgery. We also recorded the classification of patients' physical status
according to the American Society of Anesthesiologists (ASA) and details about
admission to the intensive care unit (ICU). Patients were interviewed to note the
number of days before returning to work and their ability to maintain their
previously held jobs. RESULTS: Fifty patients were included in the study, and
their mean age was 46.3 +/- 12.6 years. The median time to return to work was 195
days. Twelve patients (24 %) lost their jobs and 17 (34 %) resumed their previous
job with a change of tasks. ICU admission and time from trauma to definitive
surgery were negatively correlated with return to the previously held job.
Returning to the same job tasks was not associated with any of the factors
investigated. Polytrauma, ICU admission, and time from trauma to definitive
surgery were associated with longer leaves of absence. CONCLUSIONS: Work
reintegration after pelvic ring injuries is a major issue for patients and health
care systems: 58 % of patients were not able to return to or lost their job.
Factors correlated with leaves of absence were injury severity, delayed
definitive fixation, and ICU admission. LEVEL OF EVIDENCE: IV (case series).
PMID- 26416032
TI - Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+
lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia.
AB - Indolent lymphomas in the pediatric population were discussed during the 2014
European Association for Haematopathology/Society of Hematopathology workshop in
Istanbul, Turkey. This session was focused on pediatric-type follicular lymphoma
(FL), and its differential diagnosis with the newly recognized entity of
IRF4/MUM1+ lymphomas mainly involving Waldeyer's ring. The differential diagnosis
between t(14;18) negative FL grade 1/2 and pediatric-type FL in adults was
highlighted. The overlapping pathological and clinical features between FL and
nodal marginal zone lymphoma (NMZL) in children and young adults were recognized
and morphologic and immunophenotypical criteria helpful for the differential
diagnosis were presented. Both pediatric-type FL and NMZL are indolent processes
that should be distinguished from atypical lymphoid hyperplasia of the tonsils
and lymph nodes. The demonstration of a B cell monoclonal population by molecular
studies is strongly recommended for the diagnosis. Recognition of these indolent
variants to avoid overtreatment was emphasized. Whereas most indolent lymphomas
in the pediatric population show characteristic clinical, pathologic, and genetic
features that differ from the adult counterpart, other rare indolent lymphoid
tumors such as chronic lymphocytic leukemia (CLL) have similar characteristics.
In this report, novel findings, areas of special interest, and diagnostic
challenges emerging from the cases submitted to the workshop will be discussed.
PMID- 26416033
TI - GREMLIN 2 Mutations and Dental Anomalies.
AB - Isolated or nonsyndromic tooth agenesis or hypodontia is the most common human
malformation. It has been associated with mutations in MSX1, PAX9, EDA, AXIN2,
EDAR, EDARADD, and WNT10A. GREMLIN 2 (GREM2) is a strong bone morphogenetic
protein (BMP) antagonist that is known to regulate BMPs in embryogenesis and
tissue development. Bmp4 has been shown to have a role in tooth development.
Grem2(-/-) mice have small, malformed maxillary and mandibular incisors,
indicating that Grem2 has important roles in normal tooth development. Here, we
demonstrate for the first time that GREM2 mutations are associated with human
malformations, which include isolated tooth agenesis, microdontia, short tooth
roots, taurodontism, sparse and slow-growing hair, and dry and itchy skin. We
sequenced WNT10A, WNT10B, MSX1, EDA, EDAR, EDARADD, AXIN2, and PAX9 in all 7
patients to rule out the effects of other ectodermal dysplasias and other tooth
related genes and did not find mutations in any of them. GREM2 mutations exhibit
variable expressivity even within the same families. The inheritance is autosomal
dominant with incomplete penetrance. The expression of Grem2 during the early
development of mouse teeth and hair follicles and the evaluation of the likely
effects of the mutations on the protein structure substantiate these new
findings.
PMID- 26416035
TI - Role of of Nuclear Medicine in the multidisciplinary management of prostate
cancer.
PMID- 26416034
TI - CD44 single nucleotide polymorphism and isoform switching may predict gastric
cancer recurrence.
AB - BACKGROUND AND OBJECTIVES: The clinical implications of single nucleotide
polymorphisms (SNPs) in CD44 remain unclear. This study examined the
relationships of CD44 SNPs with clinicopathological parameters and prognosis in
Japanese gastric cancer patients. METHODS: The CD44 SNPs were analyzed in 11
gastric cancer cell lines and 517 clinical specimens. The expression of CD44
standard (CD44s) and CD44 variant 9 isoform (CD44v9) transcripts were measured by
quantitative real-time polymerase chain reaction. RESULTS: The CD44 rs187116 A/A,
A/G, and G/G genotypes were present in 10.3%, 45.1%, and 44.7% of patients,
respectively. The presence of CD44 rs187116 A/G or G/G genotypes was
significantly associated with positive peritoneal washing cytology (P = 0.012).
Disease-free survival of patients with these genotypes was significantly worse
than in those with the A/A genotype (P = 0.039). Multivariate analysis showed
that the CD44 rs187116 was independently prognostic of disease-free survival (P =
0.047). The CD44s/CD44v9 ratio was significantly lower in patients with the CD44
rs187116 A/A genotype than in those with the A/G (P = 0.046) and G/G (P = 0.047)
genotypes. CONCLUSIONS: The CD44 rs187116 genotype could predict disease
recurrence in Japanese gastric cancer patients, and the SNP was associated with
CD44 isoform switching.
PMID- 26416036
TI - Fluorodeoxyglucose positron emission tomography in pulmonary carcinoid tumors.
AB - AIM: The role of fluorodeoxyglucose positron emission tomography (FDG-PET) as an
additional investigation to computer tomography for pulmonary carcinoid tumors
remains controversial. The aim of this study was to assess the role of FDG-PET
for the diagnosis and staging of pulmonary carcinoid tumors. METHODS: We
performed a retrospective mono-institutional analysis of data from 97 patients
with pathologically confirmed pulmonary carcinoid tumor who had been operated on
between July 1998 and April 2009 and had had a preoperative FDG-PET scan
performed. RESULTS: Sixty-five (67%) of the 97 tumors were typical (TC) and 32
(33%) atypical (AC) carcinoid tumors. Overall FDG-PET sensitivity was 67% being
lower for TC (60%) than for AC (81%) (P=0.04). FDG-PET negative tumors were
smaller than FDG-PET positive tumors, with a respective median size of 15 and 17
mm (P=0.02). Median SUVmax for FDG-PET-positive tumors was 4.0 (2.8-5.1) with no
difference between TC and AC tumors. Median Ki-67 expression was respectively
4.7% and 3.1% for FDG-PET positive and FDG-PET negative tumors (P=0.05). During a
median follow-up of 49 months (interquartile range 30-63 months), 9 patients
(4TC, 5AC) developed recurrent disease. Neither SUVmax nor Ki-67 expression
resulted associated with disease-free survival. CONCLUSION: With an overall
sensitivity of 67%, FDG-PET has shown to be useful in the preoperative work-up of
patients with suspect lung carcinoid tumors. In particular it could have a role
in larger tumors. These results warrant a prospective evaluation of FDG-PET in
the staging of lung carcinoid tumor.
PMID- 26416037
TI - A quantitative study about thyroid stunning after diagnostic whole-body scanning
with 74 MBq 131I in patients with differentiated thyroid carcinoma.
AB - AIM: The aim of this paper was to explore by a quantitative method whether a 74
MBq 131I scanning activity produces a stunning effect in patients with
differentiated thyroid carcinoma (DTC). METHODS: We included 70 patients with DTC
who had their first radioiodine treatment for ablation of thyroid remnants and/or
metastases. All the patients received 1850~7400 MBq 131I. Before ablation, 34
patients (group A) performed a diagnostic scan (Dscan) 24 hours after the
administration of 74 MBq 131I; 36 patients (group B) received 131I therapy
without a previous Dscan. A therapeutic scan (Tscan) was performed after the
ablation. The fractional concentrations of 131I in remnants or functional
metastases were quantified on Dscan and Tscan, and were expressed as Dx and Tx
respectively. The level of significance was set at 0.05. RESULTS: For group A, 67
foci were found both on Dscan and Tscan, the mean Dx and Tx was 26.13+/-37.98 and
7.46+/-10.63 (P=0.000), respectively. For group B, 70 foci were found on Tscan,
the mean Tx was 15.23+/-17.23, which was higher than group A significantly
(P=0.002). CONCLUSION: 74 MBq 131I for diagnostic scan can decrease the uptake of
131I by thyroid remnants or metastases, the thyroid stunning exists.
PMID- 26416038
TI - VEGAWES: variational segmentation on whole exome sequencing for copy number
detection.
AB - BACKGROUND: Copy number variations are important in the detection and progression
of significant tumors and diseases. Recently, Whole Exome Sequencing is gaining
popularity with copy number variations detection due to low cost and better
efficiency. In this work, we developed VEGAWES for accurate and robust detection
of copy number variations on WES data. VEGAWES is an extension to a variational
based segmentation algorithm, VEGA: Variational estimator for genomic
aberrations, which has previously outperformed several algorithms on segmenting
array comparative genomic hybridization data. RESULTS: We tested this algorithm
on synthetic data and 100 Glioblastoma Multiforme primary tumor samples. The
results on the real data were analyzed with segmentation obtained from Single
nucleotide polymorphism data as ground truth. We compared our results with two
other segmentation algorithms and assessed the performance based on accuracy and
time. CONCLUSIONS: In terms of both accuracy and time, VEGAWES provided better
results on the synthetic data and tumor samples demonstrating its potential in
robust detection of aberrant regions in the genome.
PMID- 26416039
TI - Reply to "Serum high-sensitivity C-reactive protein in patients with obstructive
sleep apnea with special reference to metabolic syndrome" by Kawada (Letter to
the Editor).
PMID- 26416040
TI - Alternated intra-arterial and intravitreal chemotherapy for advanced intraocular
retinoblastoma: preliminary successful results without systemic chemotherapy.
AB - To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra
arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma.
This non-comparative interventional case series retrospectively reviewed the
medical records of six patients who presented within months of each other with
unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in
the affected eye. After clinical and ophthalmoscopic evaluation, they underwent
MRI to exclude local and CNS dissemination. The IAC was given to treat retinal
masses and intravitreal injections to treat vitreous seeding. Patients had
received two cycles (six infusions) of IAC, and from six up to ten melphalan
injections into the vitreous, with an interval of 7-10 days between them. From
one to four intravitreal injections were performed for partial remission or
consolidation. No permanent complications of procedures have been reported. All
patients underwent to bimonthly MRI examination, during treatment and every 3
months for 1 year after last injection, to exclude orbital dissemination.
Successful control (100 %) of tumor masses and vitreous seeds was achieved in all
cases at 12 months follow-up. Complications were posterior lens opacity, acute
ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous
hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No
intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up
range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for
advanced retinoblastoma allowed to provide retinal and vitreous seed control.
PMID- 26416041
TI - Prognostic impact of tumor lymphocytic infiltrates in patients with breast cancer
undergoing neoadjuvant chemotherapy.
AB - PURPOSE: The presence of a pronounced tumor lymphocytic infiltrate (TLI) is
deemed to reflect the presence of an immunoinflammatory response against the
tumor and may thus have prognostic significance. We investigated the prognostic
value of TLI detected in pathological specimens collected following neoadjuvant
chemotherapy (NACT) in patients with breast cancer. METHODS: 100 consecutive
patients with breast cancer (mean age 47.8+/-11.4 years) who were scheduled to
undergo anthracycline-and/or taxane-containing NACT were enrolled. Specimens
collected after NACT were scored with the 4-point Klintrup scoring criteria for
the presence of TLI. RESULTS: 60 patients had low-grade TLI and 40 high-grade
TLI. Comparison of the patient population according to low-grade vs high-grade
TLI revealed statistically significant difference both in terms of disease-free
survival (DFS) (log rank-4.28, p<0.05) and overall survival (OS) (log rank=3.96,
p<0.05), with high-grade TLI patients showing a better prognosis. Multivariate
Cox regression analysis identified postoperative tumor size and low-grade TLI as
the two main independent adverse prognostic factors. CONCLUSION: High-grade TLI
may interfer with tumor growth and can represent a favorable prognostic factor in
women with breast cancer undergoing NACT.
PMID- 26416042
TI - Evolution of treatment and high-risk features in resectable locally advanced Head
and Neck squamous cell carcinoma with special reference to extracapsular
extension of nodal disease.
AB - The employment of surgery as a single treatment modality for patients with
resectable locally advanced head and neck squamous cell carcinoma (HNSCC) has
been associated with high rates of locoregional recurrences even after adequate
resection. The addition of postoperative radiotherapy (RT) as adjuvant to
surgical resection for advanced HNSCC was investigated in an effort to decrease
locoregional failure rates and improve treatment outcome. The unsatisfactory
results in terms of locoregional control (LRC) and survival rates achieved with
postoperative RT in patients with high-risk features have led to the necessity of
exploring the role of concurrent chemotherapy in the adjuvant treatment in
resectable advanced HNSCC with confirmed presence of high-risk pathological
features. Two prospective randomized independent trials designed and conducted by
Radiation Therapy Oncology Group (RTOG) and the European Organization for
Research and Treatment of Cancer (EORTC) demonstrated that the addition of
cisplatin-based chemotherapy improved LRC and disease-free survival (DFS).
Significant improvement in overall survival (OS) with the use of postoperative
concurrent chemoradiotherapy (CCRT) was observed in the EORTC trial. High-risk
pathological features in patients with resected head and neck cancer representing
adverse prognostic factors that are predictive for local and/or regional
recurrence are related to the primary tumor and/or metastatic lymph nodes in the
neck. Extracapsular extension (ECE) of nodal disease in the neck has been
confirmed as a high-risk pathological feature negatively influencing LRC and
survival in patients treated with either postoperative RT or postoperative CCRT.
This article reviews the historical progress in the management of resectable
locally advanced HNSCC and the impact of ECE on clinical outcome in patients
treated with adjuvant therapy following surgery. It can be concluded that strong
evidence exists for an improved outcome for high-risk resected patients treated
with adjuvant CCRT. Precise definition of the presence of ECE is highly
recommended in order to provide proper selection of patients who would benefit
from the postoperative CCRT.
PMID- 26416043
TI - The effect of obesity on recurrence pattern in early breast cancer patients.
AB - PURPOSE: Obesity is a well known risk factor for breast cancer recurrence and
poor prognosis. We studied the effect of body mass index (BMI) on recurrence
pattern in early breast cancer patients. METHODS: This retrospective cross
sectional study analyzed the data of 2731 early stage breast cancer patients.
Patients who had metastatic disease at the time of diagnosis and with unknown BMI
values were excluded from study (N=276). Patients were classified into three BMI
categories: normal body weight, overweight, and obese. The recurrent/metastatic
sites of patients were grouped in 8 categories: local, contralateral, lymph node,
bone, lung, liver, brain and others. The association between first relapse site
of early breast cancer patients and BMI categories were evaluated. RESULTS: The
median patient age was 48 years (range 18-92). The median follow up time was 40
months (range 1-284). During follow-up, 469 (17.1%) patients developed recurrence
and/or metastasis. Of 2455 total patients, 853 (34.6%) were classified as having
normal weight, 898 (36.2%) were overweighted and 704 (29.2%) were obese. In the
whole patient group no relation between metastatic sites and BMI groups was
noticed. The first primary metastatic sites were also not associated with BMI
groups in pre and postmenopausal subpopulations. In obese patients, disease free
survival (DFS) was shorter compared to normal weighted patients, but the
difference was not significant. There was no significant difference between site
specific DFS in relation to BMI categorization. Obese and overweighted patients
had significantly shorter overall survival (OS) compared to the normal-weight
group (p=0.003). CONCLUSION: Although obesity had no effect on recurrence pattern
of early breast cancer patients, obese early breast cancer patients had shorter
OS compared to their normal-weight counterparts.
PMID- 26416044
TI - Hepatic steatosis is associated with higher incidence of liver metastasis in
patients with metastatic breast cancer; an observational clinical study.
AB - PURPOSE: To investigate the relationship between hepatic steatosis (HS) (at the
time of diagnosis) and hepatic metastasis (at the time of diagnosis and follow
up) in metastatic breast cancer (BC) patients by using computed tomography (CT).
METHODS: A total of 107 metastatic BC patients who had an abdominal CT were
retrospectively enrolled in this study. Patients without HS (N=79) were regarded
as the control group and those with HS constituted the HS study group (N-28).
RESULTS: Hepatic metastases at diagnosis and during follow-up were more common in
patients with HS (p=0.018 and p=0.041, respectively) and in the premenopausal
group (p<0.001 and p=0.004, respectively), whereas they were similar in patients
with and without HS in the postmenopausal group (p=0.655 and p=0.656,
respectively). Overall survival rates were similar in patients with and without
HS (p=0.606). CONCLUSION: Hepatic metastases at diagnosis and during follow-up
were more frequent in patients with HS, especially in premenopausal patients.
Survival was similar in both groups.
PMID- 26416045
TI - Lack of association between +405 G/C polymorphism in VEGF and breast cancer risk:
A meta-analysis.
AB - PURPOSE: To explore whether the vascular endothelial growth factor (VEGF) +405
G/C polymorphism confers susceptibility to breast cancer (BC) by conducting a
meta-analysis. METHODS: Publications addressing the association between the VEGF
+405 G/C polymorphism and BC risk were selected from the PubMed, Embase and
Google Scholar databases. Data were extracted from studies by three independent
reviewers. The meta-analysis was performed by STATA 12.0 software, and odds ratio
(OR) with 95% confidence interval (CI) were calculated. RESULTS: Finally, 10 case
control studies were retrieved with a total of 8,855 BC patients and 9,393
controls. No significant association was identified between VEGF +405 G/C
polymorphism and BC risk in overall populations under 5 models (C vs G: OR=1.001,
95% CI=0.896-1.119, p=0.987; CC vs GG: OR=1.006, 95% CI=0.853-1.186, p=0.997; CG
vs GG: OR= 0.985, 95% CI=0.823-1.178, p=0.779; CC vs CGs/GG: OR=1.019, 95%
CI=0.921-1.127, p=0.722; CC/CG vs GG: OR=0.985, 95% CI=0.835-1.162, p=0.862), and
also in the subgroup analysis by ethnicity. CONCLUSION: Our study confirms that
there is a lack of association between the VEGF +405 G/C polymorphism and BC
risk.
PMID- 26416046
TI - Epidemiological and clinicopathological characteristics of BRCA-positive and BRCA
negative breast cancer patients in Greece.
AB - PURPOSE: BRCA mutation carriers can benefit from targeted clinical interventions.
On the other hand, families with evident aggregation of breast cancer (BC) cases
and a BRCA-negative genetic test can still be considered as of elevated risk,
since the underlying genetic factor remains unidentified. In the present study,
we compared clinical and demographic characteristics between BRCA1 mutation
carriers (BRCA1mut) and non-carriers (non-BRCA1) in a Greek group of BC patients
(n=321). METHODS: Data were collected and analyzed from 321 women with BC, with
131 patients screened for pathogenic mutations in the high-penetrant genes BRCA1
and BRCA2. Collected data included demographics, pedigrees, tumor histopathology
and immunohistochemistry findings. RESULTS: In BRCA1mut patients, their mothers
and grand- mothers were diagnosed at a younger age compared to non-BRCA1
carriers. Additionally, BRCA1mut patients were diagnosed with mainly estrogen
receptor (ER) negative (p<0.001), Her-2 negative (p<0.05) and triple negative
(p<0.01) tumors. The youngest generation was diagnosed with familial breast
cancer (FBC) 9.7 years earlier than their mothers (p<0.001). Age at BC diagnosis
negatively correlated with the nuclear grade of breast tumors (r=-0.3, p<0.05).
Among parous individuals, the number of full-term pregnancies significantly
correlated with the age at BC onset (r=0.19, p<0.05). CONCLUSION: Despite their
similarities, FBC cases with identified BRCA1 mutations exhibit a clearly
distinct profile. We have identified an anticipation effect in FBC patients, with
significantly reduced age at diagnosis in younger generations. Increased parity
seems to prevent early BC onset. This is the first study comparing clinical and
demographic characteristics of FBC BRCA1mut and non-carriers in a Greek cohort.
PMID- 26416047
TI - Genetic polymorphisms in cell cycle regulatory genes CCND1 and CDK4 are
associated with susceptibility to breast cancer.
AB - PURPOSE: This study was performed to screen cyclin D1 (CCND1) and cyclin
dependent kinases (CDK4) genes in order to evaluate their association with breast
carcinogenesis. METHODS: The germline screening of these genes was carried out by
combining polymerase chain reaction (PCR) and single-strand conformation
polymorphism (SSCP), followed by DNA sequence analysis. A total of 400
individuals (200 breast cancer patients and 200 healthy controls) were recruited
prospectively for this study. RESULTS: Sequence analyses of the coding region of
CCND1 revealed 12 mutations. When analyzed, a significant association was found
between CCND1 mutations and breast cancer. It was observed that a 6-fold
increased breast cancer risk (odds ratio/OR=5.75, 95% confidence interval/CI=1.26
26.33) was associated with Cys7Tyr in breast cancer patients when compared with
healthy controls. In addition, a 5-fold increased breast cancer risk was
associated with Trp63Stop mutation (OR=5.44, 95% CI=1.82-16.23), 10861C>A
(OR=4.84; 95% CI=1.60-14.58) and 7720insTT (OR=5.32, 95% CI=1.98-14.23) in breast
cancer patients compared to healthy controls. Concerning CDK4 gene, 5 mutations
were identified and a significant association was observed between CDK4 gene
mutations and breast cancer. It was observed that a 6-fold increased risk of
breast cancer (OR=5.71, 95% CI=0.29-4.65) was associated with 5693 T>A. In
addition, a 5-fold increased risk of breast cancer (OR=5.05, 95% CI=2.17-11.78)
was associated with 5732 G>A in breast cancer patients compared to controls.
CONCLUSION: In this study, our results showed that CCND1 and CDK4 mutations are
associated with an increased risk of breast cancer, and may serve as biomarkers
for early diagnosis and detection of breast cancer.
PMID- 26416048
TI - Ipsilateral in-breast tumor recurrence after breast conserving therapy: true
recurrence versus new primary tumor.
AB - PURPOSE: To classify ipsilateral in-breast cancer recurrences (IBCR) in patients
treated with conservative surgery and radiation therapy, either as new primary
tumor (NP) or true recurrence (TR) and to assess the prognostic and therapeutic
importance of this classification. METHODS: The records of 107 patients treated
for local tu- mor recurrence after breast-conserving therapy (BCT) at the
National Cancer Center, Sofia, between March 1999 and May 2011 were
retrospectively analysed. The patients'primary tumors were up to 2 cm in size.
For their primary tumors all patients underwent quadrantectomy, axillary lymph
node dissection and postoperative radiotherapy (RT) up to 50 Gy. In cases with
nodal metastasis additional RT has been used. Adjuvant chemotherapy and
hormonotherapy have been used according to the clinical indications and depending
of the patient's condition. Every attempt was made to define a tumor as a TR or
NP, based on the changes in location and histology. (99m)Tc-MIBI SPECT-CT was
used to localize the site of recurrence. RESULTS: Forty-four (41.1%) of the
relapses were TR and 63 (58.9%) NPs. Out of 63 relapses defined as NPs, 54
(85.7%) changed the location and 49 (68.3%) had a different histology. The age of
patients with TR and with NP did not differ significantly at the time of
diagnosis of the primary tumor (TR 48.8+/-10.45 years vs NP 50.8+/-10.56;
p<0.330), but those who developed TR were significantly younger than those with
NP at the time of recurrence (TR 53 years, 66+/-11.1 vs NP 58.15+10.6; p<0.05).
Recurrences defined as NPs, developed after a significantly longer period of time
in comparison to the TRs (7.4+/-2.6 years vs 4.8+/-2.2 years; p<0.0001). Five
year overall survival of patients with TR was significantly lower compared to
patients with NP (31.8% vs 96.7% p=0.0001). CONCLUSIONS: Recurrences developing
after BCT represent different clinical events, having different origin, prognosis
and, therefore, requiring different type of treatment. It seems that a
significant part of the recurrences that develop in the residual parenchyma,
following BCT, are new carcinomas.
PMID- 26416050
TI - Quality of life in colorectal cancer patients: an Izmir Oncology Group (IZOG)
study.
AB - PURPOSE: To investigate the variables of quality of life (QoL) among Turkish
patients with colorectal cancer (CRC). METHODS: In this prospective study we
investigated the QoL of Turkish CRC patients. Two hundred and twenty two patients
with CRC were included. The sociodemographic form and European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
were used. RESULTS: The study group consisted of 142 males (64%) and 80 females
(36%). The mean patient age was 55.68+/-11.387 years. The majority of the
patients (36.9%) had local disease while advanced-stage disease and locally
advanced stage disease had 32.2% and 28.8% of the patients; respectively. The
mean QoL score was moderate (62.81+/- 27.0). The most common complaints were
fatigue, economic difficulties and constipation. Gender, education level and
disease stage were associated with QoL. Physical, role and social functioning
were more adversely affected in female patients. Compared to women, men had
significantly more favorable global QoL (p=0.044). Some functional scales were
worse in advanced disease compared to other stages.These outcomes were
statistically significant in the functional scales of global health (p=0.007),
physical (p=0.03), cognitive (p=0.01) and emotional function (p=0.007). Patients
with advanced disease had worse outcomes in some symptoms (nausea, vomiting,
dyspnea, loss of appetite and financial distress). CONCLUSIONS: Female gender and
advanced disease were strongly associated with poorer QoL among Turkish CRC
patients.
PMID- 26416049
TI - Clinical presentation and management of gastro-intestinal and pancreatic
secondary metastatic tumors.
AB - PURPOSE: As progress regarding the treatment has occurred over recent years in
oncology, more patients with metastatic disease are presented for diagnosis and
further management. The purpose of this study was to reveal the incidence,
location and to describe the clinical characteristics and outcome in a series of
patients diagnosed with pancreatic, small and large bowel metastatic tumors that
underwent metastasectomy. METHODS: A total of 12 patients (7 male and 5 female)
diagnosed with extrahepatic gastrointestinal (GI) and pancreatic metastases from
2001 to 2013 were operated for resection of secondary metastatic tumors to the
small and large bowel and the pancreas. Four out of 12 patients were asymptomatic
and a secondary tumor was detected during follow up. RESULTS: The median interval
revealing the metastatic tumor since the management of the primary tumor was 6.5
years (range 1-27). Primary tumors were malignant melanoma (4 patients), renal
cell carcinoma (RCC; 2 patients), leiomyosarcoma of the uterus (2 patients),
lobular breast cancer, mesenchymal chondrosarcoma of the skull, endometrial
adenocarcinoma and a non-Hodgkin lymphoma (one case each). The median follow-up
was 15 months (range 4-120). CONCLUSIONS: Metastatic secondary tumors have to be
considered especially when the patient's medical history includes a previous
malignancy. They may also occasionally present as the initial manifestation of an
occult primary lesion leading to diagnostic difficulty. Although radical surgery
is the most effective approach, treatment and survival grossly depend on
histological type and the stage of the primary disease. Hence, management of
these patients should be individualized by a multidisciplinary team.
PMID- 26416051
TI - Factors influencing cost, length of hospital stay and mortality in colorectal
cancer.
AB - PURPOSE: Colorectal cancers (CRCs) are the most common cancers in the world after
lung and prostate cancer in men and breast and lung cancer in women, and usually
occur in the recto-sigmoid region. There are many factors that affect their
morbidity and mortality. Some markers have been evaluated to predict disease
prognosis. However, a gold standard prognostic biomarker has not yet been found
for CRC. In the present study, we aimed to evaluate the factors associated with
the duration and cost of hospital stay and mortality. METHODS: Patients who were
admitted to the emergency service and general surgery clinic with abdominal pain,
rectal bleeding, weight loss, diminished stool discharge, and ileus were included
in this study. Recorded were patient age, gender, comorbid factors, family
history, surgical treatment procedure, elective or urgent surgical intervention,
bowel cleansing before surgery, pathological stage, neutrophil/lymphocyte ratio
(NLR), red cell distribution width (RDW), mean platelet volume (MPV) and CEA, CA
19.9 and hemoglobin levels. RESULTS: The mean patient age was 61.2+/-12.4 years.
The male/female ratio was 0.596(81/136). Emergency surgery was an independent
factor increasing the cost and length of hospital stay (p=0.007 and p=0.018).
Additionally, patients >65 years of age had increased length of hospital stay and
mortality (p=0.008 and p=0.024, respectively). Anemic patients had 50% higher
mortality risk compared with patients with normal hemoglobin levels (p=0.030).
CONCLUSION: Based on our results, anemic patients in the geriatric population who
underwent emergency CRC surgery may have higher costs, longer hospital stay and
greater mortality rates than other CRC patients.
PMID- 26416052
TI - Significance of serum and bile tumor markers in the diagnostic approach of
patients with malignant pancreatobiliary disease.
AB - PURPOSE: Serum and bile tumor markers are under intense scrutiny for the
diagnosis of malignant disease. The purpose of our study was to report the
usefulness of serum and bile tumor markers for the discrimination between benign
and malignant pancreatobiliary diseases. METHODS: Between March 2010 and May
2013, 95 patients with obstructive jaundice or history of biliary obstruction,
were included in the study. During ERCP, bile samples were obtained for
measurement of tumor markers CEA, CA19- 9, CA125, CA72-4 and CA242. Serum samples
were taken before ERCP for the same measurements. The patients were divided into
two groups: patients with malignant disease and patients with benign disease.
RESULTS: Serum tumor marker levels were significantly higher in patients with
malignant disease. Serum CA242 and CA19-9 exhibited the highest diagnostic
accuracy (76.8% and 73.7%, respectively). CA125 and CA72-4 levels in bile samples
were significantly higher in patients with malignant disease. Bile CA125, CEA and
CA72-4 achieved the best diagnostic accuracy (69, 65 and 65), respectively). The
combined detection of CA19-9, CA242 in serum and CA125, CA72-4 in bile along with
total bilirubin levels, showed the best diagnostic accuracy (81%). CONCLUSIONS:
Serum and bile tumor markers, when studied alone, lack the diagnostic yield to
discriminate benign from malignant pancreatobiliary diseases. In cases of
diagnostic dilemmas the combination of serum and bile markers might be helpful.
PMID- 26416053
TI - Transcatheter arterial chemoembolization combined with microwave coagulation
therapy and the perioperative care for patients with hepatocellural carcinoma.
AB - PURPOSE: To explore the value of artificial hydrothorax microwave coagulation
combined with transcatheter arterial chemoembolization (TACE) therapy in the
treatment of ultrasound-invisible malignant tumors in the hepatic dome (mainly
hepatocellular carcinoma/HCC) and the perioperative care for the patients.
METHODS: Sixty-eight patients with malignant liver tumors in the hepatic dome
were treated with a combination therapy of TACE and microwave coagulation via an
artificially induced hydrothorax. Their perioperative condition was under close
observation and the nursing care was intensified. Paracentesis of the chest was
successfully carried out via the positioning of ultrasound and guidance of
microwave to the tumor site, so that the tumor could be treated with cold cycle
microwave coagulation therapy. RESULTS: After treatment, 3/68 patients (4.4%)
achieved complete tumor ablation, while 59/68 (86.8%) achieved tumor ablation
>50% or tumor shrinkage >30%. Another 6/68 patients (8.8%) achieved tumor
ablation <50% or tumor shrinkage <30%. Of 45 patients, 42 (93.3%) obtained a
reduction of AFP level >50% post-therapy, 28/37 patients (75.7%) achieved a
reduction of CEA level >50%, 23/29 patients (79.3%) achieved a reduction of CA19
9 level> 50%; 3/68 patients (4.4%) survived for 4 to 6 months, 31/68 (45.6%)
survived >6 months and 34/68 (50%) survived >12 months. No bleeding, liver
failure, infection or needle tract seeding occurred after the operation, and no
treatment-related deaths occurred. CONCLUSION: Microwave coagulation combined
with TACE for HCC in the hepatic dome is safe and effective. Perioperative
observation and nursing care can not only reduce the complications but also
improve the therapeutic effect and the patient quality of life.
PMID- 26416055
TI - Laparoscopic left lateral hepatectomy for colorectal metastasis is the standard
of care.
AB - PURPOSE: Over the last decade, laparoscopic liver surgery has significantly
evolved. The aim of this study was to analyse the outcomes of Laparoscopic Left
Lateral Hepatectomy (LLLH) for colorectal cancer (CRC) metastases in a tertiary
referral hepato-pancreato-biliary centre. METHODS: A consecutive series of
patients undergoing LLLH between January 2009 and April 2013 were analysed using
prospectively collected data in a tertiary referral HPB centre. In particular,
the study focused on patients who had LLLH for colorectal liver metastasis
(CRLM). The following features were analysed: operative time, intraoperative
blood loss, number and size of tumours, resection margins, complication rates,
follow up period and recurrence rates. RESULTS: A total of 17 patients were
finally included. There were no bile leaks or collections and no postoperative
bleeding. The median hospital stay was 4 days (range 2-10). The median size of
the metastatic lesions was 28.1 mm (range 8-56). The resection was R0 in all
except 2 patients (11%) where the margin was less than 1 mm. The mean resection
margin was 14.6 mm (range 1-50). Eight patients (47%) did not develop any
recurrence till latest follow up. Seven patients (41%) developed recurrence in
the liver or lungs. The median time to recurrence was 11 months (range 2-12).
There was only one death in the follow up period (22-77 months). Sixteen patients
(94%) were alive at the latest follow up. CONCLUSION: LLLH for CRLM is safe and
can be performed with low complication rates, adequate resection margins, short
hospital stay, and oncologic outcomes similar to those of open surgery.
PMID- 26416054
TI - In vivo study of the effect of combining endostatin gene therapy with 32P-colloid
on hepatocarcinoma and its functioning mechanism.
AB - PURPOSE: To investigate the therapeutic effect of combining 32P colloid
radiotherapy with endostatin anti-angiogenesis therapy on hepatocellular
carcinoma (HCC) cells. METHODS: HCC mouse models were prepared using H22 cells
and randomly divided into four groups. The mice were administered phosphate
buffered saline (PBS), (32)Pcolloid, secretory endostatin encoding plasmid and
combination of 32P and endostatin, respectively. Seven, 14 and 21 days after
treatment the mice were sacrificed. Expression of endostatin was confirmed using
western blot. Tumor growth rate, microvessel density (MVD) in the solid tumor and
apoptotic index (AI) of tumor cells was analyzed using immunohistochemistry and
TUNEL methods. RESULTS: (1): From the western blot results, 1400 bp endostatin
specific protein bands were observed in the samples from groups 3 and 4, but not
in the other two groups; (2): The tumor growth rate of groups 2, 3 and 4 was
significantly decreased compared to group 1 and that of group 4 was significantly
lower than group 2 and 3 (3): The MVD of group 1 was greatly higher than in the
other groups (4): The AI of group 4 was dramatically higher than in the other
groups. CONCLUSIONS: (32)Pcolloid radiotherapy or endostatin anti-angiogenesis
therapy were able to inhibit the growth of HCC cells in vivo, while the
combination of (32)P and endostatin showed much better therapeutic effect in HCC
treatment.
PMID- 26416056
TI - Evaluation of c-kit (CD 117) expression as a prognostic factor in testicular germ
cell tumors: an Izmir Oncology Group (IZOG) study.
AB - PURPOSE: Despite the successful use of targeted and molecular therapies in other
cancers, little progress has been made in the management of testicular germ cell
tumors (TGCTs). c-kit (CD 117) is a good target for cancer treatment and
possesses an impressive role in the current oncological practice. We aimed to
evaluate c-kit expression in early stage TGCTs as a prognostic factor. METHODS:
Patients with TGCTs who were referred to the Medical Oncology Clinic and
underwent curative surgical operation were included in our study before starting
chemo- therapy. Immunohistochemistry was performed on formalin-fixed and paraffin
embedded three-micrometer thick sections with CD 117 Rabbit Anti c-kit in vitro
gene kit. Biochemically, we utilized AFP and beta-HCG Immunlite 2000 device with
solid phase chemiluminescent immunometric method, and LDH Roche models with the
DP-standardized UV method. AFP 0-15 ng/ml, beta-HCG < 0.1 mlu/ml and LDH 240-480
mg/dl were considered as normal values. RESULTS: Sixty-five patients were
included in our study. Forty-one (63%) patients had non-seminoma tumors (NSGCTs)
and 24 (37%) had seminoma. Statistically significant c-kit expression was found
in patients with seminoma (p<0.0001). There was no difference between negative or
positive c-kit expression in terms of clinicopathological characteristics,
including preoperative serum levels of AFP, beta-HCG, LDH, lymph node
involvement, distant metastasis, and IGCCCG risk classification. No correlation
was found between these parameters and 5-year progression free survival (PFS)
rate except for tumor stage, presence of lymph node metastasis and IGCCCG score
(p=0.001, p=0.04, and p=0.0001, respectively). Five-year PFS rate of patients
with positive CD 117 was 72.2% (95% CI, 54.6-89.8), and 56.6% (95% CI, 31.2-82.1)
for those without CD 117 expression involvement (p=0.12). CONCLUSION: So far,
there has been no significant breakthrough in the treatment of cisplatin
refractory TGCTs in the era of targeted therapies. No prognostic importance of c
kit expression has been found in our study. However, we believe that c-kit
expression, in numerical terms, can be considered as a good prognostic factor for
patients with TGCTs. The fact that all seminoma cases displayed positive c-kit
expression is what we think has driven this result.
PMID- 26416057
TI - Combination of adjuvant radiotherapy and androgen deprivation therapy after
radical prostatectomy in high risk prostate cancer patients - results from
retrospective analysis.
AB - PURPOSE: We retrospectively evaluated the outcome in prostate cancer (PCa)
patients receiving combination of adjuvant radiotherapy (ART) and androgen
deprivation therapy (ADT) after radical prostatectomy (RP). METHODS: Between 2004
and 2012, 132 patients were referred for ART to the Department of Oncology,
University Hospital, Split. Fifty-six consecutive patients with at least one
proven or possible adverse prognostic factor such as pelvic lymph nodes invasion
(LNI), lymphovascular invasion (LVI), high tumor grade and high preoperative
prostatic specific antigen (PSA) level received combination of ART and ADT, while
76 patients received ART alone. The ADT consisted of a luteinizing hormone
releasing hormone (LHRH) agonist or bicalutamide at a dose of 150 mg per day. The
duration of ADT was left at the discretion of the treating physician and it
lasted 6 to 36 months (median 24).The effect of combination of ART and ADT on
biochemical relapse-free survival (bRFS), metastases-free survival (mFS), disease
specific survival (DSS) and overall survival (OS) was estimated using the Kaplan
Meier method. RESULTS: After a median follow-up time of 61 months (range 13.6
113), the 5- and 7-year bRFS were 90.5 and 77.2%, respectively. Distant relapse
occurred in 5 patients, resulting in 5- and 7-year mFS of 95.9 and 81.7%,
respectively. During follow-up, 7 patients died (2 PCa deaths), resulting in 5-
and 7-year DSS and OS of 100% and 94.7% and 90.6 and 81.5%, respectively.
CONCLUSIONS: This retrospective study shows high bRFS, mFS, DSS and OS rates with
the combination of ART and ADT in high-risk PCa patients.
PMID- 26416058
TI - Robotic-assisted radical prostatectomy - the 5-year Romanian experience.
AB - PURPOSE: Radical prostatectomy is the standard therapeutic approach for localized
prostate cancer. After the implementation of robotic surgery in Romania, the
indication extended progressively to locally advanced prostate cancer. Our
objective was to evaluate the oncological and functional outcomes in patients
undergoing robotic-assisted radical prostatectomy (RARP), 5 years after the first
intervention in Romania. METHODS: Between November 2009 and July 2014, 207 RARPs
were performed using the da Vinci SI Surgical System. Perioperative data were
prospectively collected. The oncological and functional follow-up was up to 55
months (range 3-55). RESULTS: Patient stratification according to D'Amico risk
categories was 16% low risk, 56.7% intermediate risk and 27.3% high risk. Median
console time was 210 min (range 160-360). Median blood loss was 300 ml (range 50
1300), transfusion being required in 2.9% of the cases. Histopathological
examinations showed pT3 in 40.8% of the cases, with a positive surgical margin
rate of 21.1%, 13.6% for pT2, and 32.1% for pT3. Continence rate (0-1 daily
safety pad) at 6, 12, 24 and 55 months was 88.3, 88.8, 90.1, and 93.7%
respectively. Overall sexual function restoration rate at 6, 12, 24 and 55 months
was 41.1, 44.4, 47.4 and 53%, respectively. Biochemical recurrence rate during
follow-up was 6.9%. CONCLUSIONS: RARP is a minimally invasive therapeutic
approach for prostate cancer, with acceptable outcomes, even in countries such as
Romania, where the detection rate for localized prostate cancer is lower compared
to other European countries due to lack of national screening programs.
PMID- 26416059
TI - Association of p16 gene methylation with prostate cancer risk: a meta-analysis.
AB - PURPOSE: The tumor suppressor gene p16 is frequently silenced and inactivated by
hypermethylation in human cancers, including prostate cancer. However, the
association between the methylation status of p16 and prostate cancer risk
remains ambiguous. This study aimed to assess the association of p16 methylation
with prostate cancer risk by a comprehensive metaanalysis. METHODS: Relevant
studies were identified by searching PubMed, Embase and Web of Science databases
before October 2014 with no restrictions. The strength of the association between
p16 methylation and prostate cancer risk was assessed by combined odds ratio (OR)
and 95 % confidence interval (CI). The between-study heterogeneity and the
contributions of single studies to the final results were tested by chi-square
based Q test and sensitivity analyses, respectively. Publication bias was
evaluated by funnel plots. RESULTS: A total of 1,296 samples from 12 independent
studies were enrolled in the present metaanalysis. Overall, a significant
association was observed between p16 methylation and prostate cancer risk
(OR=3.06; 95% CI:1.34- 6.98;p=0.008). Stratified analyses by ethnic groups
further revealed that prostate cancer risk was increased for individuals carrying
the methylated p16 compared with those with unmethylated p16 in Caucasian
populations (OR=2.51;95% CI:1.01-6.26;p=0.047) and Asian populations (OR=9.50;95%
CI:1.78-50.61;p=0.008). CONCLUSIONS: This study identified a strong association
of p16 methylation with prostate cancer risk and suggested that p16 methylation
might be a potential biomarker for prostate cancer.
PMID- 26416060
TI - Interfraction variation in prostate cancer - analysis of 11726 cone-beam CT.
AB - PURPOSE: To investigate the setup margins in prostate cancer treatment without
using daily online repositioning methods. METHODS: We analysed the data from
patients treated with curative-intend radiotherapy. Each patient underwent a
series of pretreatment online localizations during daily setup using conebeam CT.
The skin-prostate shifts and bone-prostate shifts were recorded in
anteroposterior (AP), craniocaudal (CC), and laterolateral (LL)direction. The
safety margins based on van Herk equation (2.5Sigma+0.7sigma) were calculated and
the correlations between margins and various patient characteristics and prostate
locations were investigated. RESULTS: A total of 307 patients were included,
representing 11,726 localisations resulting in 70,356 shifts. The man skin
prostate setup inaccuracy was 0.8 +/- 5.4mm in AP, 1.3 +/- 4.8mm for CC, and 0.1
+/- 5.6mm in LL direction. The man bone-prostate setup inaccuracy was 0.4 +/-
3.3mm in AP, 0.1 +/- 2.5mm for CC, and 0.1 +/- 1.4mm in LL direction. According
to van Herk equation, clinical target volume (CTV)-planning target volume (PTV)
margins of 11.4, 10.6, and 11.8 mm (AP, CC, and LL, respectively) would be
required for setup using skin markers and margins of 7.0, 4.7, and 2.1mm would be
necessary for setup using bone structures. The average rectal area < 11cm(2) and
volume of bladder > 300 cm(3) were associated with smaller CTV-PTV margins for
setup using bone structures. The largest margins (15.8 mm in LL direction) were
needed in patients with body mass index (BMI) > 35 using skin markers.
CONCLUSIONS: Our results confirm that the commonly used CTV-PTV margins are
inadequate.
PMID- 26416061
TI - Clinical significance of nucleostemin and proliferating cell nuclear antigen
protein expression in non-small cell lung cancer.
AB - PURPOSE: To investigate the expression and significance of the expression of
nucleostemin (NS) and proliferating cell nuclear antigen (PCNA) protein in non
small cell lung cancer (NSCLC). METHODS: Immunohistochemistry (streptavidin
peroxidase method) was used to detect NS and PCNA expression in 53 NSCLC samples
and 15 normal lung samples. RESULTS: NS protein expression was detected in 54.7%
(29/53) of the NSCLC samples and 0% (0/15) of the normal lung samples (p<0.01).
Furthermore, the positive expression rate of PCNA was 6.67% (1/15) in normal lung
samples and 71.7% (38/53) in NSCLC samples (p<0.05). Also, the NS protein
expression rate was 65.2% (15/23) in adenocarcinoma tissue samples, significantly
higher than that in squamous tissues, where the NS expression rate was 46.7%
(14/30) (p<0.05). In addition, the NS expression rate of 42.9% (15/35) in well or
moderately differentiated tumor tissues was lower than the rate of 77.8% (14/18)
in poorly differentiated tumor tissues (p<0.05). The grade of differentiation had
no correlation with tumor-node-metastasis (TNM) stage and lymph node metastasis
(p>0.05). Also, the positive expression rate of PCNA was significantly higher in
NSCLC samples than in normal lung samples (p<0.05). In addition, a positive
correlation was found between NS and PCNA expression in NSCLC (p<0.05).
CONCLUSION: The highly valuable tumor molecular markers, NS and PCNA, had higher
expression levels in NSCLC samples. Combined detection of NS and PCNA may be
important for the early diagnosis of lung cancer and individualized therapy,
having also an important role in predicting tumor prognosis.
PMID- 26416062
TI - Wnt/beta-catenin signaling pathway in lung cancer stem cells is a potential
target for the development of novel anticancer drugs.
AB - PURPOSE: In the present study, we have analyzed the regulation of Wnt/beta
catenin signaling in lung adenocarcinoma stem cells (CSCs), that are responsible
for tumor recurrence. METHODS: Lung cancer samples were studied for the presence
of cancer stem like cells and analyzed by flow cytometry. Then, the sorted cells
were analyzed for the stem cell surface markers and Wnt/beta-catenin signaling
pathways. Moreover, the sorted side population (SP) and non-SP cells were also
subjected to drug resistance assay. RESULTS: Western blot analysis showed that
the protein level of beta-catenin was highly upregulated in fluorescence
activated cells (FACs) sorted SP cells which led to elevated expression of stem
cell protein Oct-4 that is responsible for SP cells' self-renewal. RT-PCR
revealed that the relative mRNA expression level of Wnt target gene cyclin D was
significantly higher (p<0.01) in SP cells, enhancing thus the cell proliferation
rate and clone formation efficiency. In addition, the matrigel invasion assay
revealed that SP cells were highly invasive than non-SP cells. CONCLUSION: In the
present study we demonstrated that lung adenocarcinoma samples contain a small
population of tumor-initiating SP cells which possess the characteristic features
of CSCs. Wnt/beta-catenin mediated increased expression of beta-catenin, Oct-4
and cyclin D in SP cells but not in non-SP cells was also observed. FACs-purified
SP cells are resistant to a number of chemotherapeutic drugs. Our data suggest
that the use of novel anticancer drugs, targeting Wnt/beta-catenin signaling
pathways, may help eradicate the lung cancers stem cells.
PMID- 26416063
TI - Expression and clinical contribution of MRGD mRNA in non-small cell lung cancers.
AB - PURPOSE: MAS-related G protein-coupled receptor, member D (MRGD) has been
reported to be involved in tumorigenesis in vivo. However, the clinical role of
MRGD in non-small cell lung cancer (NSCLC) remains unclarified. The purpose of
the current study was to detect the expression of MRGD mRNA in NSCLC formalin
fixed (FF), paraffin-embedded (PE) tissues and to investigate the
clinicopathological significance of the MRGD level in NSCLC patients. METHODS:
The expression of MRGD mRNA was examined in 125 NSCLC tissue samples together
with paired para-noncancerous FF/PE tissues by using real time quantitative PCR
(qRT-PCR). Furthermore, the relationship between MRGD level and
clinicopathological parameters of NSCLC was analyzed. RESULTS: The average level
of MRGD in NSCLC tumor tissues (1.0682+/-0.6096) was remarkably higher than that
in the adjacent non-cancerous lung tissue (0.3994+/-0.2838, p<0.001). The area
under curve (AUC) of receiver operating characteristic curve (ROC) of MRGD mRNA
was 0.853 (95% CI: 0.808-0.898, p(0.001). Moreover, the level of MRGD mRNA was
found to be correlated to lymph node metastasis (r=0.219, p=0.014), tumor size
(r=0.221, p=0.013) and clinical TNM stage (r=0.187, p=0.037). Finally, the
survival of patients in high MGRD expression group was 7.94+/-9.85 months,
remarkably shorter than that of the low expression group (20.84+/-1.19 months,
p=0.049). CONCLUSIONS: MRGD may be a vital diagnostic and prognostic factor in
NSCLC. MRGD possesses the potential to become a new target for the molecular
therapy of NSCLC.
PMID- 26416064
TI - Inhibition of tumor necrosis factor alpha using RNA interference in oral squamous
cell carcinoma.
AB - PURPOSE: Oral squamous cell carcinoma (OSCC) is a disease with increased
prevalence and unfavorable prognosis calling for development of novel therapeutic
strategies. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory
cytokine implicated in the development and progression of cancer. The present
study was designed to assess the impact of TNF-alpha specific inhibition using
small interference RNA (siRNA) in SSC-4 cells, a representative model for OSCC.
METHODS: The present study evaluated the effect of TNF-alpha inhibition using
siRNA as inhibitory mechanism on SCC-4 cells. The study focused on the effect of
TNF-alpha inhibition on apoptosis, autophagy and invasion in parallel with a
panel of 20 genes involved in apoptosis and angiogenesis. RESULTS: TNF-alpha
inhibition was related with reduction of cell viability, activation of apoptosis
and autophagy in parallel with the inhibition of migration in SCC-4 cells.
Evaluating the impact on gene expression levels, inhibition of FASL-FADD,
NFkappaB, SEMA 3C, TNF-alpha, TGFB1, VEGFA, along with activation of PDGFB and
SEMA 3D was observed. Our study confirms the important role of TNF-alpha and
sustains that it might be a therapeutic target in OSCC. CONCLUSIONS: TNF-alpha is
a key mediator of the immune system, with important role in OSCC tumorigenesis,
and might be considered as a therapeutic target using siRNA technology,
particularly for those risk cases having FASL/FADD overexpressed.
PMID- 26416065
TI - Cardiac tumors: a retrospective multicenter institutional study.
AB - PURPOSE: Primary cardiac tumors are uncommon but not extremely rare. Cardiac
tumors, mostly intracavitary, include benign and malignant tumors that arise from
the endocardium, heart valves or myocardium. This retrospective study summarizes
the experience of the Cardiac Surgery Departments of three tertiary Hospitals in
this field, and particularly in cardiac myxomas, over the last 29 years. Herein,
we present the results of cardiac tumors excision in relation to postoperative
morbidity and mortality. METHODS: Between 1985 and 2014, 117 patients, aged from
16 to 82 years, underwent resection of a cardiac tumor. RESULTS: Ninety one of
the tumors (77.78%) were myxomas, 15 of them (12.82%) were other primary cardiac
tumors, 7 of them (5.98%) were infra-diaphragmatic tumors and the remaining 4
tumors (3.42%) were benign intracavitary masses (thrombi). Patients operated on
for a cardiac tumor had a 30-day mortality rate of 3.29%. Atrial fibrillation
appeared in 21 out of 91 patients (23.07%) operated on for cardiac myxoma, while
neurological complications were observed in 3 patients (3.29%). Re-exploration
for bleeding was performed in 5 out of 91 cases (5.49%) and recurrence occurred
in 4.39% of myxomas. CONCLUSIONS: Despite being rare, primary cardiac tumors
require open heart intervention soon after their diagnosis in order to prevent
complications and achieve low mortality rates.
PMID- 26416066
TI - Evaluation of mycosis fungoides management by total skin electron beam therapy
with "translational technique".
AB - PURPOSE: The aim of this study was to evaluate the outcomes of total skin
electron beam therapy (TSEBT) with "translational technique" in the management of
mycosis fungoides (MF). METHODS: Between January 1995 and October 2014, 51
patients with MF were treated using TSEBT with translational technique. The total
dose was 2800-3600 cGy, de-livered in 7 to 20 fractions. Out of the total 51
patients, 22 (43.1%) had T2 (generalized patch/plaque) disease, 20 (39.3%) had T3
disease (tumor stage), and 9 (17.6%) had T4 (erythrodermic) disease. Radiation
related late skin injury parameters including atrophy, pigmentation changes, hair
loss, telangiectasia and ulceration were assessed according to RTOG/EORTC Late
Radiation Morbidity Scoring Schema after at least 3 months from TSEBT. RESULTS:
Treatment response was categorized as complete remission (CR), partial remission
(PR), or non-responding (NR) lesions. After TSEBT with translational technique,
CR rate was 68.6% and PR rate 23.5%, while the NR rate was 7.9%. Overall, the
rates of grade 1, grade 2, grade 3, and grade 4 toxicity were 17.6% )9 patients),
39.3% (20 patient), 35.3% (18 patients), and 7.8% (4 patients), respectively. At
a median follow-up of 79 months (range 14-142), overall survival (OS) and disease
free survival (DFS) rates were 83% and 46%, respectively. CONCLUSION: For
patients with MF refractory to topical chemotherapy and phototherapy, TSEBT with
translational technique offers excellent local control (LC: CR+PR) and favorable
OS rates along with substantial relief of symptoms.
PMID- 26416067
TI - Splenic irradiation as palliative treatment for symptomatic splenomegaly due to
secondary myelofibrosis: a multi-institutional experience.
AB - PURPOSE: To evaluate the impact of splenic irradiation as a palliative treatment
for symptomatic splenomegaly due to secondary myelofibrosis. METHODS: Seventeen
patients with chronic myelogenous leukemia and 3 with idiopathic polycythaemia
presented with splenomegaly, splenic pain and anemia. Due to symptomatic
splenomegaly, despite first-line treatment, the patients underwent splenic
irradiation. Two patients received two different schedules of external
radiotherapy (580 cGy in 5 fractions and 600 cGy in 6 fractions). Eight patients
received 980 cGy in 14 fractions. Ten patients received two courses of 360 cGy in
6 fractions, 3 months apart. Median follow-up was 12 months post irradiation.
RESULTS: The patients showed excellent response to treatment one month post
radiotherapy, while treatment was well tolerated without severe toxicity. The
dimensions of the spleen decreased significantly. Pain-related Visual Analogue
Score (VAS) regressed after completion of irradiation. During 12-month follow-up
all patients maintained the benefit of radiotherapy. CONCLUSION: This study
indicates that splenic irradiation could be a safe and effective palliative
treatment for symptomatic splenomegaly due to secondary myelofibrosis.
PMID- 26416068
TI - Cutaneous melanoma in Turkey: analysis of 1157 patients in the Melanoma Turkish
Study.
AB - PURPOSE: To develop a large Turkish National Melanoma registry in order to define
demographic and clinicopathologic characteristics of patients with melanoma.
METHODS: The data was collected from 1635 patients with melanoma through a web
based registry system in 22 centers. Herein we present the results of 1157
patients with cutaneous melanoma. RESULTS: The patient median age was 56.4 years
and 646 (55.8%) were males. The commonest subtype was superficial spreading type
(357, 30.9%). The commonest primary site was the lower extremities (N=353,
30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only
104 (12.5%) patients had a thickness <1mm. Among 694 patients with available
data, 136 (19.6%) presented with stage 4 disease while the most frequent stage
was stage 3, encountered in 393 (56.6% patients). CONCLUSION: Our melanoma
registry is the largest in our country providing a snapshot view of cutaneous
melanoma and its care. Our patients presented with more advanced stages and they
had worse prognosis compared to SEER database.
PMID- 26416069
TI - Association of heme oxygenase-1 polymorphisms with cancer risk: A systematic
review and meta-analysis.
AB - PURPOSE: Observational studies have recently focused on the association between
heme oxygenase-1 (HMOX1) gene promoter polymorphisms and cancer risk. However,
conflicting results have been obtained. To derive a precise estimate of the
association, a systematic review and meta-analysis were conducted. METHODS: This
study followed the guidelines for Preferred Reporting Items for Systematic
Reviews and Meta-Analyses. PubMed, Medline, Embase and Web of Knowledge were
systematically searched for relevant studies. Summary odds ratios (ORs) and 95%
confidence intervals (CIs) were calculated for the allelic and genotypic
comparisons according to the homozygous, heterozygous, dominant, and recessive
genetic models. Between-study heterogeneity was quantified through I2 statistics,
and publication bias was appraised by using funnel plots. Sensitivity analyses
were conducted to evaluate the robustness of the meta-analysis findings. RESULTS:
Meta-analysis of 9 studies involving 2491 cases and 3380 controls did not reveal
any significant association of the HMOX-1 (GT)n and 413A>T polymorphisms with
cancer risk. Stratified analysis by ethnicity showed a statistically significant
association between (GT)n repeat length variant and susceptibility to cancer for
the heterozygous genetic model among Asian populations (OR=1.42, 95% CI: 1.04
1.95, Pheterogeneity=0.218), which is a robust finding according to sensitivity
analysis. Funnel plot inspection did not reveal any publication bias. CONCLUSION:
In conclusion, this study comprehensively examined the available literature on
the association of HMOX-1 (GT)n and 413A>T polymorphisms with cancer risk. Meta
analysis results suggest (GT)n repeat length polymorphism as a potential
susceptibility variant for cancer in Asians. Additional large-scale and well
designed studies are needed to confirm these results.
PMID- 26416070
TI - Stereotactic body radiation therapy patient specific quality assurance using a
two-dimensional array at extended source to surface distance.
AB - METHODS: Five patients with 38 fields have been analyzed in this study. The plans
were optimized for the following clinical sites: one liver, one lung, one brain,
one prostate and one spine. The detector array used for the measurements was the
PTW Seven29 array. All the plans were optimized and calculated using Eclipse
v8.9. The center of the array was setup at 215 cm from the source and all the
fields were measured and analyzed one by one. All the 30 measurements were
performed on a NovalisTX linear accelerator equipped with a high definition
multileaf collimator. The evaluation was based mainly on gamma index passing
rates using 2 mm distance to agreement (DTA) and 2% dose difference. RESULTS: The
accuracy of the Eclipse Treatment Planning System (TPS) at extended Source to
Surface Distances (SSDs) using an ionization chamber was measured to be within
1.0%. All the field measurements were performed and analyzed 35 individually. The
percent of the points that had a gamma index of less than 1 using 3%/3 mm was
>99% for all the measurements. In order to better evaluate our process and
distinguish smaller differences a new set of results was obtained by applying
gamma index tolerances of 2%/2mm. In this case, the gamma index passing rates
ranged from 90.8 to 100% (95.5%+/-3%). The profile comparison showed that the
detector array measurements followed closely the calculated 40 profiles, even for
fields optimized with multiple peaks and valleys. CONCLUSION: The choice of the
IMRT QA device has an important role in the results of the patient specific QA of
the delivered dose to the patient in the case of small targets as in the
treatment of spinal targets. In this study, we demonstrated that an extended SSD
measurement can improve the sampling resolution of a two-dimensional (2D)
detector array, in our case the PTW 45 Seven29 array. This method was shown to be
accurate and efficient for measuring highly modulated small fields for pre
treatment patient specific QA.
PMID- 26416071
TI - Primary thyroid lymphoma: The two ends of the spectrum.
AB - We describe two different cases of prinary thyroid lymphoma (PTL). PTL is a rare
malignancy. Nevertheless, it frequently presents diagnostic and therapeutic
challenges. The first patient, a 79-year-old female, presented with a large,
painless thyroid mass accompanied by severe obstructive symptoms of the upper
respiratory and gastrointestinal track. The second patient (67-year-old female)
presented with nodular goiter. Thyroidectomy - performed on the first patient for
alleviation of obstructive symptoms - revealed the presence of a diffuse large B
cell lymphoma. Although she was administered standard chemotherapy she deceased
four months later. In the second patient, primary thyroid lymphoma was an
incidental finding following thyroidectomy performed for nodular goiter. These
two cases illustrate the variable course of PTL, the possibility of which should
be kept into consideration in clinical practice.
PMID- 26416072
TI - Early start of adjuvant chemotherapy in breast cancer.
PMID- 26416073
TI - Extremely high level of CA 19-9 in a patient with metastatic pancreatic cancer
and chronic renal failure- Second highest level of CA 19-9 in the literature.
PMID- 26416074
TI - Avenzoar's (1091-1162) clinical description of cancer.
AB - In the 11(th) and 12(th) century the Western caliphate flourished, making Cordoba
the capital of physicians and philosophers. During that period lived and
practised the famous physician Ibn Zuhr or Avenzoar. In his monumental treatise
Al Taysir, Avenzoar provided the first clinical description of a polypoid
colorectal tumour as well as the case of a uterine cancer and a basal cell
carcinoma. His medical work remained popular through middle ages, influencing the
development of western medicine.
PMID- 26416075
TI - Cost effectiveness and resource allocation of Plasmodium falciparum malaria
control in Myanmar: a modelling analysis of bed nets and community health
workers.
AB - BACKGROUND: Funding for malaria control and elimination in Myanmar has increased
markedly in recent years. While there are various malaria control tools currently
available, two interventions receive the majority of malaria control funding in
Myanmar: (1) insecticide-treated bed nets and (2) early diagnosis and treatment
through malaria community health workers. This study aims to provide practical
recommendations on how to maximize impact from investment in these interventions.
METHODS: A simple decision tree is used to model intervention costs and effects
in terms of years of life lost. The evaluation is from the perspective of the
service provider and costs and effects are calculated in line with standard
methodology. Sensitivity and scenario analysis are undertaken to identify key
drivers of cost effectiveness. Standard cost effectiveness analysis is then
extended via a spatially explicit resource allocation model. FINDINGS: Community
health workers have the potential for high impact on malaria, particularly where
there are few alternatives to access malaria treatment, but are relatively
costly. Insecticide-treated bed nets are comparatively inexpensive and modestly
effective in Myanmar, representing a low risk but modest return intervention.
Unlike some healthcare interventions, bed nets and community health workers are
not mutually exclusive nor are they necessarily at their most efficient when
universally applied. Modelled resource allocation scenarios highlight that in
this case there is no "one size fits all" cost effectiveness result. Health gains
will be maximized by effective targeting of both interventions.
PMID- 26416076
TI - Repairing the basic defect in cystic fibrosis - one approach is not enough.
AB - Cystic fibrosis has attracted much attention in recent years due to significant
advances in the pharmacological targeting of the basic defect underlying this
recessive disorder: the deficient functional expression of mutant cystic fibrosis
transmembrane conductance regulator (CFTR) chloride channels at the apical
membrane of epithelial cells. However, increasing evidence points to the reduced
efficacy of single treatments, thus reinforcing the need to combine several
therapeutic strategies to effectively target the multiple basic defect(s).
Protein-repair therapies that use potentiators (activating membrane-located CFTR)
or correctors (promoting the relocation of intracellular-retained trafficking
mutants of CFTR) in frequent mutations such as F508del and G551D have been put
forward and made their way to the clinic with moderate to good efficiency.
However, alternative (or additional) approaches targeting the membrane stability
of mutant proteins, or correcting the cellular phenotype through a direct effect
upon other ion channels (affecting the overall electrolyte transport or simply
promoting alternative chloride transport) or targeting less frequent mutations
(splicing variants, for example), have been proposed and tested in the field of
cystic fibrosis (CF). Here, we cover the different strategies that rely on novel
findings concerning the CFTR interactome and signalosome through which it might
be possible to further influence the cellular trafficking and post-translational
modification machinery (to increase rescued CFTR abundance and membrane
stability). We also highlight the new data on strategies aiming at the regulation
of sodium absorption or to increase chloride transport through alternative
channels. The development and implementation of these complementary approaches
will pave the way to combinatorial therapeutic strategies with increased benefit
to CF patients.
PMID- 26416077
TI - Bordetella filamentous hemagglutinin and fimbriae: critical adhesins with
unrealized vaccine potential.
AB - Pertussis, or whooping cough, is a highly contagious respiratory disease that is
caused by the Gram-negative bacterium Bordetella pertussis, which is transmitted
exclusively from human to human. While vaccination against B. pertussis has been
successful, replacement of the whole cell vaccine with an acellular component
vaccine has correlated with reemergence of the disease, especially in adolescents
and infants. Based on their presumed importance in mediating adherence to host
tissues, filamentous hemagglutinin (FHA) and fimbria (FIM) were selected as
components of most acellular pertussis vaccines. In this review, we describe the
biogenesis of FHA and FIM, recent data that show that these factors do, in fact,
play critical roles in adherence to respiratory epithelium, and evidence that
they also contribute to persistence in the lower respiratory tract by modulating
the host immune response. We also discuss shortcomings of whole cell and
acellular pertussis vaccines and the possibility that FHA and FIM could serve as
effective protective antigens in next-generation vaccines.
PMID- 26416079
TI - Heterotopic ossification in the submental triangle remote from the vascular
pedicle after reconstruction with a fibular free flap: a previously unreported
complication.
AB - Fibular free flaps are routinely used to reconstruct segmental mandibular defects
after resection. While ossification of the vascular pedicle is uncommon but well
reported, to our knowledge, heterotopic ossification remote from the pedicle has
not previously been described. We report a case in which this occurred. It serves
as a reminder that bony, hard lumps in the neck can present years after
reconstruction with a fibular flap.
PMID- 26416078
TI - Bacterial nucleators: actin' on actin.
AB - The actin cytoskeleton is a key target of numerous microbial pathogens, including
protozoa, fungi, bacteria and viruses. In particular, bacterial pathogens produce
and deliver virulence effector proteins that hijack actin dynamics to enable
bacterial invasion of host cells, allow movement within the host cytosol,
facilitate intercellular spread or block phagocytosis. Many of these effector
proteins directly or indirectly target the major eukaryotic actin nucleator, the
Arp2/3 complex, by either mimicking nucleation promoting factors or activating
upstream small GTPases. In contrast, this review is focused on a recently
identified class of effector proteins from Gram-negative bacteria that function
as direct actin nucleators. These effector proteins mimic functional activities
of formins, WH2-nucleators and Ena/VASP assembly promoting factors demonstrating
that bacteria have coopted the complete set of eukaryotic actin assembly
pathways. Structural and functional analyses of these nucleators have revealed
several motifs and/or mechanistic activities that are shared with eukaryotic
actin nucleators. However, functional effects of these proteins during infection
extend beyond plain actin polymerization leading to interference with other host
cell functions such as vesicle trafficking, cell cycle progression and cell
death. Therefore, their use as model systems could not only help in the
understanding of the mechanistic details of actin polymerization but also provide
novel insights into the connection between actin dynamics and other cellular
pathways.
PMID- 26416080
TI - Metastases from the lung presenting as a parotid lump.
AB - We report a case of a 59-year-old man who presented with a preauricular facial
lump that was suspected to be a parotid malignancy based on fine needle
aspiration. A chest radiograph and a computed tomogram showed a mass in the lungs
and several metastases, and caused a diagnostic dilemma as to the origin of the
parotid mass, which was later confirmed to be metastatic disease that had arisen
from a carcinoma of unknown origin. Infraclavicular metastasis to the parotid is
rare but should not be overlooked particularly in patients who present with
coexisting conditions, or when cytological findings are atypical.
PMID- 26416082
TI - Reviewing the Role of Resveratrol as a Natural Modulator of Microglial
Activities.
AB - Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a natural phytoalexin found in
grape-skin, exerts multiple biological activities, including anti-inflammatory,
antiproliferative and antioxidant effects. In the past few years, mounting
evidence has suggested that resveratrol is neuroprotective against a number of
neurological diseases. An important contributor to the pathogenesis of
neurological disorders is neuroinflammation, of which microglial activation is an
important hallmark. It is possible that M1/M2 polarization of microglia may play
an important role in controlling the balance between promoting and resolving
neuroinflammation in the CNS. Immunomodulatory strategies capable of redirecting
the microglial response toward the neuroprotective M2 phenotype could offer
attractive options for neurodegenerative diseases with inflammatory components.
The neuroprotective actions of resveratrol seem to be attributable to its anti
inflammatory properties, due not only to its direct scavenger effects versus
toxic molecules but also to a capacity to upregulate natural anti-inflammatory
defences, thus counteracting excessive responses of classically activated M1
microglia. The goal of this review is to summarize recent insights into the
therapeutic potential of resveratrol as a natural modulator of microgliamediated
neurotoxicity.
PMID- 26416081
TI - Examining inequalities in uptake of maternal health care and choice of provider
in underserved urban areas of Mumbai, India: a mixed methods study.
AB - BACKGROUND: Discussions of maternity care in developing countries tend to
emphasise service uptake and overlook choice of provider. Understanding how
families choose among health providers is essential to addressing inequitable
access to care. Our objectives were to quantify the determinants and choice of
maternity care provider in Mumbai's informal urban settlements, and to explore
the reasons underlying their choices. METHODS: The study was conducted in
informal urban communities in eastern Mumbai. We developed regression models
using data from a census of married women aged 15-49 to test for associations
between maternal characteristics and uptake of care and choice of provider. We
then conducted seven focus group discussions and 16 in-depth interviews with
purposively selected participants, and used grounded theory methods to examine
the reasons for their choices. RESULTS: Three thousand eight hundred forty-eight
women who had given birth in the preceding 2 years were interviewed in the
census. The odds of institutional prenatal and delivery care increased with
education, economic status, and duration of residence in Mumbai, and decreased
with parity. Tertiary public hospitals were the commonest site of care, but there
was a preference for private hospitals with increasing socio-economic status.
Women were more likely to use tertiary public hospitals for delivery if they had
fewer children and were Hindu. The odds of delivery in the private sector
increased with maternal education, wealth, age, recent arrival in Mumbai, and
Muslim faith. Four processes were identified in choosing a health care provider:
exploring the options, defining a sphere of access, negotiating autonomy, and
protective reasoning. Women seeking a positive health experience and outcome
adopted strategies to select the best or most suitable, accessible provider.
CONCLUSIONS: In Mumbai's informal settlements, institutional maternity care is
the norm, except among recent migrants. Poor perceptions of primary public health
facilities often cause residents to bypass them in favour of tertiary hospitals
or private sector facilities. Families follow a complex selection process,
mediated by their ability to mobilise economic and social resources, and a
concern for positive experiences of health care and outcomes. Health managers
must ensure quality services, a functioning regulatory mechanism, and monitoring
of provider behaviour.
PMID- 26416083
TI - Elucidating the spatio-temporal dynamics of an emerging wildlife pathogen using
approximate Bayesian computation.
AB - Emerging pathogens constitute a severe threat for human health and biodiversity.
Determining the status (native or non-native) of emerging pathogens, and tracing
back their spatio-temporal dynamics, is crucial to understand the eco
evolutionary factors promoting their emergence, to control their spread and
mitigate their impacts. However, tracing back the spatio-temporal dynamics of
emerging wildlife pathogens is challenging because (i) they are often neglected
until they become sufficiently abundant and pose socio-economical concerns and
(ii) their geographical range is often little known. Here, we combined classical
population genetics tools and approximate Bayesian computation (i.e. ABC) to
retrace the dynamics of Tracheliastes polycolpus, a poorly documented pathogenic
ectoparasite emerging in Western Europe that threatens several freshwater fish
species. Our results strongly suggest that populations of T. polycolpus in France
emerged from individuals originating from a unique genetic pool that were most
likely introduced in the 1920s in central France. From this initial population,
three waves of colonization occurred into peripheral watersheds within the next
two decades. We further demonstrated that populations remained at low densities,
and hence undetectable, during 10 years before a major demographic expansion
occurred, and before its official detection in France. These findings corroborate
and expand the few historical records available for this emerging pathogen. More
generally, our study demonstrates how ABC can be used to determine the status,
reconstruct the colonization history and infer key evolutionary parameters of
emerging wildlife pathogens with low data availability, and for which samples
from the putative native area are inaccessible.
PMID- 26416084
TI - The effects of intervention based on supportive leadership behaviour on Iranian
nursing leadership performance: a randomized controlled trial.
AB - AIMS: To assess the effects of a workshop on supportive leadership behaviour
(SLB) on the performance of head nurses, using a randomized controlled trial
design. BACKGROUND: The effect of transformational leadership on SLB in nursing
management is emphasised. METHODS: A total of 110 head nurses working at
university hospitals were included randomly in two control and intervention
groups. The head nurses in the intervention group participated in supportive
leadership training, but the control group did not. Performance in supportive
leadership was assessed with a validated instrument, which six subordinates used
to assess their head nurse (n = 731). RESULTS: There was a significant difference
in SLB scores from baseline to the 3 month follow-up (P < 0.0001). Moreover, the
post-intervention scores were significantly higher in the intervention group,
compared with the control group (P < 0.0001). The results showed that in the
intervention group, the effect sizes were greater for males (50%) than for
females (36%) and greater for married participants (42%) than for single
participants (37%). CONCLUSION: The workshop on supportive leadership behaviour,
particularly the interactive multifaceted training, improved the leadership
performance of the head nurses who participated in this study. IMPLICATIONS FOR
NURSING MANAGERS: Health policy decision makers should apply SLB, which is a
significant leadership style, to improve the outcomes in other groups of health
care management, such as physicians. Future studies are needed to investigate the
effects of such workshops in longer periods of follow up.
PMID- 26416085
TI - Will a second biopsy sample affect treatment decisions in patients with chronic
hepatitis B?
AB - BACKGROUND AND AIM: Liver biopsy is the gold standard for assessment of fibrosis
in patients with hepatitis B. However, it has some disadvantages, including inter
observer and intra-observer variability in biopsy interpretation and specimen
variation. A standard biopsy specimen represents only about 0.0002 % of the whole
liver. It has been shown that two biopsy samples collected during a procedure
have significant influence on the diagnostic performance of interpretation in
patients with hepatitis C or non-alcoholic steatohepatitis. Therefore, we aimed
to assess the influence of collecting two liver biopsy samples during a single
procedure for staging and grading chronic hepatitis B. PATIENTS AND METHODS: 27
patients were included in the study. The median age of the patients was 43.51 +/-
11.69. Fifteen patients were female, 12 patients were male. In the biopsy
procedure, two samples of liver lobes were obtained. Grade and stage scores were
compared between the two samples. Fibrosis staging and grading were assessed
according to the Ishak scoring system. RESULTS: Numbers of portal tract and
biopsy size were equal in the two samples. There was a significant difference
between the samples in terms of histological activity index (p value = 0.04).
However, the difference was not enough to distinguish the mild and moderate
stages. On the other hand, no significant difference in fibrosis staging between
the two samples was found. CONCLUSIONS: With this relatively small size of
patients, in this study, we showed that a proper liver biopsy size is sufficient
to predict treatment decisions in chronic hepatitis B patients. However, further
studies are needed to show the association of sampling variability in patients
with hepatitis B.
PMID- 26416086
TI - Macroscopic ordering of helical pores for arraying guest molecules
noncentrosymmetrically.
AB - Helical nanostructures have attracted continuous attention, not only as media for
chiral recognition and synthesis, but also as motifs for studying intriguing
physical phenomena that never occur in centrosymmetric systems. To improve the
quality of signals from these phenomena, which is a key issue for their further
exploration, the most straightforward is the macroscopic orientation of helices.
Here as a versatile scaffold to rationally construct this hardly accessible
structure, we report a polymer framework with helical pores that unidirectionally
orient over a large area (~10 cm(2)). The framework, prepared by crosslinking a
supramolecular liquid crystal preorganized in a magnetic field, is chemically
robust, functionalized with carboxyl groups and capable of incorporating various
basic or cationic guest molecules. When a nonlinear optical chromophore is
incorporated in the framework, the resultant complex displays a markedly
efficient nonlinear optical output, owing to the coherence of signals ensured by
the macroscopically oriented helical structure.
PMID- 26416088
TI - Allelic diversity of KIR3DL1/3DS1 in a southern Chinese population.
AB - The inhibitory KIR3DL1 and the activating KIR3DS1 segregate as alleles of the
same locus. KIR3DL1 is highly diversified at the allele level and KIR3DL1 alleles
exhibit varied levels of expression and ligand binding affinity resulting in
varied degrees of NK cell inhibition. Previous studies have shown that the
KIR3DL1/3DS1 polymorphism associated with viral infection, cancer and
transplantation. However, little is known about the population distribution of
KIR3DL1/3DS1 alleles in Chinese. The present study examined allelic diversity of
KIR3DL1/3DS1 in a southern Chinese population (N=306) using PCR-SSP and
sequencing based typing. The presence of KIR3DL1 and KIR3DS1 were detected in
97.1% and 34.0% of the tested individuals respectively. A total of 10 KIR3DL1
alleles (including 2 novel ones) and 6 KIR3DS1 alleles (including 5 novel ones)
were identified. Common KIR3DL1 alleles (>10%) were KIR3DL1*01502 (74.8%),
KIR3DL1*00501 (23.9%) and KIR3DL1*00701 (15.7%). KIR3DS1*01301 was the
predominant KIR3DS1 allele with other KIR3DS1 alleles only sporadically observed.
The knowledge of the allelic polymorphism of KIR3DL1/3DS1 may help to better
understand the role played by KIR3DL1/3DS1 in associated diseases and clinical
transplantation in southern Chinese.
PMID- 26416087
TI - A gene feature enumeration approach for describing HLA allele polymorphism.
AB - HLA genotyping via next generation sequencing (NGS) poses challenges for the use
of HLA allele names to analyze and discuss sequence polymorphism. NGS will
identify many new synonymous and non-coding HLA sequence variants. Allele names
identify the types of nucleotide polymorphism that define an allele (non
synonymous, synonymous and non-coding changes), but do not describe how
polymorphism is distributed among the individual features (the flanking
untranslated regions, exons and introns) of a gene. Further, HLA alleles cannot
be named in the absence of antigen-recognition domain (ARD) encoding exons. Here,
a system for describing HLA polymorphism in terms of HLA gene features (GFs) is
proposed. This system enumerates the unique nucleotide sequences for each GF in
an HLA gene, and records these in a GF enumeration notation that allows both more
granular dissection of allele-level HLA polymorphism and the discussion and
analysis of GFs in the absence of ARD-encoding exon sequences.
PMID- 26416089
TI - Evolution of the hemagglutinin expressed by human influenza A(H1N1)pdm09 and
A(H3N2) viruses circulating between 2008-2009 and 2013-2014 in Germany.
AB - This report describes the evolution of the influenza A(H1N1)pdm09 and A(H3N2)
viruses circulating in Germany between 2008-2009 and 2013-2014. The phylogenetic
analysis of the hemagglutinin (HA) genes of both subtypes revealed similar
evolution of the HA variants that were also seen worldwide with minor exceptions.
The analysis showed seven distinct HA clades for A(H1N1)pdm09 and six HA clades
for A(H3N2) viruses. Herald strains of both subtypes appeared sporadically since
2008-2009. Regarding A(H1N1)pdm09, herald strains of HA clade 3 and 4 were
detected late in the 2009-2010 season. With respect to A(H3N2), we found herald
strains of HA clade 3, 4 and 7 between 2009 and 2012. Those herald strains were
predominantly seen for minor and not for major HA clades. Generally, amino acid
substitutions were most frequently found in the globular domain, including
substitutions near the antigenic sites or the receptor binding site. Differences
between both influenza A subtypes were seen with respect to the position of the
indicated substitutions in the HA. For A(H1N1)pdm09 viruses, we found more
substitutions in the stem region than in the antigenic sites. In contrast, in
A(H3N2) viruses most changes were identified in the major antigenic sites and
five changes of potential glycosylation sites were identified in the head of the
HA monomer. Interestingly, we found in seasons with less influenza activity a
relatively high increase of substitutions in the head of the HA in both subtypes.
This might be explained by the fact that mutations under negative selection are
subsequently compensated by secondary mutations to restore important functions
e.g. receptor binding properties. A better knowledge of basic evolution
strategies of influenza viruses will contribute to the refinement of predictive
mathematical models for identifying novel antigenic drift variants.
PMID- 26416090
TI - Direct Microsurgical Embolectomy for an Acute Distal Basilar Artery Occlusion.
AB - BACKGROUND: Acute basilar artery occlusion is associated with high mortality
rates, up to 35%-40%. Early revascularization by intravenous thrombolysis, intra
arterial thrombolysis, and endovascular mechanical embolectomy is considered the
best option to date. The objective of this technical report is to present the
direct microsurgical embolectomy technique for an acute distal basilar artery
occlusion as an urgent life-saving revascularization procedure. METHODS: A 71
year-old male patient suffered from an acute embolic basilar artery occlusion and
became unconscious (Glasgow Coma Scale 4). Computed tomography angiography and
MRA revealed the distal basilar artery occlusion along with an increased
diffusion-weighted imaging signal in the corresponding territory. After an
individual case discussion, the patient underwent a microsurgical embolectomy via
a frontotemporal craniotomy and an anterior temporal approach. RESULTS:
Intraoperative indocyanine green and postoperative computed tomography
angiography revealed complete revascularization of the previously occluded
basilar quadfurcation. The patient steadily recovered and was able to walk with
assistance after 4 weeks. CONCLUSIONS: Microsurgical embolectomy can be an
effective treatment option for acute distal basilar artery occlusion in selected
cases with experienced surgeons, but a critical preoperative decision-making
process is needed.
PMID- 26416091
TI - Caudal Zona Incerta/VOP Radiofrequency Lesioning Guided by Combined Stereotactic
MRI and Microelectrode Recording for Posttraumatic Midbrain Resting-Kinetic
Tremor.
AB - OBJECTIVE: Reporting the outcome of two patients who underwent unilateral
ablative stereotactic surgery to treat pharmacologic resistant posttraumatic
tremor (PTT). METHODS: We present two patients (31 and 47 years old) with
refractory PTT severely affecting their quality of life. Under stereotactic
guidance, refined by T2-weighted magnetic resonance imaging and double-channel
multiunit microelectrode recording (MER), three sequential radiofrequency lesions
were performed in the caudal zona incerta (cZi) up to the base of thalamus (VOP).
Effects of cZi/VOP lesion were prospectively rated with a tremor rating scale.
RESULTS: Both patients demonstrated intraoperative tremor suppression with
sustained results up to 18 months follow-up, with improvement of 92% and 84%,
respectively, on the tremor rating scale. Tremor improvement was associated with
enhancement functionality and quality of life for the patients. The patients
returned to their work after the procedure. No adverse effects were observed up
to the last follow-up. CONCLUSION: Radiofrequency lesion of the cZi/VOP target
was effective for posttraumatic tremor in both cases. The use of T2-weighted
images and MER was found helpful in increasing the precision and safety of the
procedure, because it leads the RF probe by relying on neighbor structures based
on thalamus and subthalamic nucleus.
PMID- 26416092
TI - Repeatability of Cone Spacing Measures in Eyes With Inherited Retinal
Degenerations.
AB - PURPOSE: To determine short-term variability of adaptive optics scanning laser
ophthalmoscopy (AOSLO)-derived cone spacing measures in eyes with inherited
retinal degenerations (IRD) and in normal eyes. METHODS: Twenty IRD patients and
10 visually normal subjects underwent AOSLO imaging at two visits separated by no
more than 1 month (NCT00254605). Cone spacing was measured in multiple macular
regions in each image by three independent graders. Variability of cone spacing
measures between visits, between graders, and between eyes was determined and
correlated with standard clinical measures. RESULTS: Cone spacing was measured in
2905 regions. Interobserver agreement was high both in normal eyes and eyes with
IRD (mean intraclass correlation coefficient [ICC] = 0.838 for normal and 0.892
for eyes with IRD). Cone spacing measures were closely correlated between visits
(ICC > 0.869 for both study groups). Mean relative intervisit spacing difference
(absolute difference in measures divided by the mean at each region) was 4.0% for
normal eyes and 4.9% for eyes with IRD. Cone spacing measures from fellow eyes of
the same subject showed strong agreement for all subjects (ICC > 0.85 for both
study groups). CONCLUSIONS: Adaptive optics scanning laser ophthalmoscopy-derived
macular cone spacing measures were correlated between observers, visits, and
fellow eyes of the same subject in normal eyes and in eyes with IRD. This
information may help establish the role of cone spacing measures derived from
images of the cone mosaic obtained with AOSLO as a sensitive biomarker for
longitudinal tracking of photoreceptor loss during disease progression and in
response to treatment. (ClinicalTrials.gov number, NCT00254605.).
PMID- 26416093
TI - Relationship Between Location of Retinal Nerve Fiber Layer Defect and Curvature
of Retinal Artery Trajectory in Eyes With Normal Tension Glaucoma.
AB - PURPOSE: To quantify the degree of curvature of the retinal artery trajectory
(RAT) and to investigate the relationship between the curvature and the location
of a retinal nerve fiber layer defect (NFLD) in eyes with normal tension glaucoma
(NTG). METHODS: This was a retrospective observational study of 88 eyes of 88 NTG
patients who had a wedge-shaped NFLD. The retinal artery trajectory and the
position of the NFLD were assessed in the fundus photographs. The course of the
supra and infratemporal retinal arteries were marked on a color fundus photograph
and fitted to a second degree polynomial curve (ax[x]/100 + bx + c) using ImageJ.
The coefficient "a" was used for the curvature of the trajectory. The proximity
of the NFLD to the fovea (supra-NFLD angle, infra-NFLD angle) was determined by
two methods. The relationship between the RAT and the supra-NFLD angle and the
infra-NFLD angle was determined by linear regression analyses. RESULTS: Fifty-six
eyes had a supratemporal NFLD and 69 eyes had an infratemporal NFLD. The
steepness of the RAT was significantly correlated with the supra-NFLD angle 1 (R
= -0.27, P = 0.041) and angle 2 (R = -0.28, P = 0.040), but not with the infra
NFLD angle 1 (R = -0.06, P = 0.61) and angle 2 (R = -0.21, P = 0.078).
CONCLUSIONS: The supratemporal NFLDs were located closer to the fovea in eyes
with the retinal artery closer to the fovea in NTG patients. The steepness of the
trajectory of the temporal retinal artery can be one predictor of the proximity
of the NFLD to the fovea.
PMID- 26416094
TI - Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences
and Predict Longitudinal Change in Attentional Control and Episodic Memory
Composites in the Adult Children Study.
AB - Cognitive measures that are sensitive to biological markers of Alzheimer disease
(AD) pathology are needed to (a) facilitate preclinical staging, (b) identify
individuals who are at the highest risk for developing clinical symptoms, and (c)
serve as endpoints for evaluating the efficacy of interventions. The present
study assesses the utility of two cognitive composite scores of attentional
control and episodic memory as markers for preclinical AD pathology in a group of
cognitively normal older adults (N = 238), as part of the Adult Children Study.
All participants were given a baseline cognitive assessment and follow-up
assessments every 3 years over an 8-year period, as well as a lumbar puncture
within 2 years of the initial assessment to collect cerebrospinal fluid (CSF) and
amyloid tracer Pittsburgh compound-B scan for amyloid imaging. Results indicated
that attentional control was correlated with levels of Abeta42 at the initial
assessment whereas episodic memory was not. Longitudinally, individuals with high
CSF tau exhibited a decline in both attention and episodic memory over the course
of the study. These results indicate that measures of attentional control and
episodic memory can be used to evaluate cognitive decline in preclinical AD and
provide support that CSF tau may be a key mechanism driving longitudinal
cognitive change.
PMID- 26416098
TI - Parental choice on normalising cosmetic genital surgery.
PMID- 26416095
TI - Hot and Cool Executive Functions in Children with Attention-Deficit/Hyperactivity
Disorder and Comorbid Oppositional Defiant Disorder.
AB - While neuropsychological deficits in both "hot" and "cool" executive functions
(EFs) have been documented among individuals with attention-deficit/hyperactivity
disorder (ADHD), these EF deficits are not universal across all individuals with
this diagnosis. One potential moderator of executive dysfunction may be the
presence of comorbid oppositional defiant disorder (ODD). This study examined the
association between "hot" and "cool" EFs and comorbid ODD in children with ADHD.
Thirty-three children with ADHD and comorbid ODD (ADHD+ODD), 67 with ADHD without
ODD (ADHD-ODD), and 30 typically developing controls participated. Children were
7-12 years of age. "Cool" EFs were assessed with a spatial span task and a card
sorting test. "Hot" EFs were assessed using a delay discounting task and a
gambling task. ADHD-ODD and ADHD+ODD groups performed more poorly on "cool" EF
tasks than controls, but did not differ from each other. Furthermore, the number
of ADHD symptoms, but not ODD symptoms, was associated with "cool" EF scores. The
three groups did not differ on "hot" EF tasks and the number of ADHD or ODD
symptoms was unrelated to "hot" EF scores. In sum, children with ADHD presented
with "cool" EF deficits which appear to be unrelated to ODD comorbidity. However,
"hot" EF deficits were not present among children with ADHD, irrespective of
comorbid ODD status.
PMID- 26416100
TI - Pharmacokinetics of clomipramine during pregnancy.
AB - PURPOSE: Clomipramine is one of the drugs for depression during pregnancy;
however, pharmacokinetic data of clomipramine and its active metabolite
desmethylclomipramine in this vulnerable period are lacking. In this study, we
describe clomipramine and desmethylclomipramine concentrations including their
ratios during pregnancy. Second, we describe Center for Epidemiologic Studies
Depression scale (CES-D) scores during pregnancy. METHODS: During 13 pregnancies,
every trimester and 3 months after pregnancy, the clomipramine and
desmethylclomipramine concentrations were measured with LC-MSMS and the severity
of depression was assessed by taking the CES-D score. All concentrations used in
our calculations were in fact the ratio between actual plasma concentration
(MUg/l) and the actual dose (mg). We compared differences in ratios between
trimesters by using the Friedman test. RESULTS: Studying 12 women and 13
pregnancies, we found no changes in mean clomipramine concentrations, a
statistically significant decrease in mean desmethylclomipramine concentrations
(p = 0.014) and a significant decrease in the ratio of
desmethylclomipramine/clomipramine mean concentrations during pregnancy (p =
0.014) compared to the post-partum period. Sub-therapeutic concentrations of
clomipramine and desmethylclomipramine were found in three patients during whole
pregnancy. CONCLUSIONS: The mean concentrations of the pharmacologically active
metabolite of clomipramine and desmethylclomipramine changes during pregnancy,
where a decrease in mean concentrations was found during pregnancy. In case of
recurrent disease, we recommend to control clomipramine and its metabolite
concentrations, while both are active.
PMID- 26416101
TI - Risk factors for potentially inappropriate prescribing to older patients in
primary care.
AB - PURPOSE: The aim of this study is to determine modifiable risk factors
contributing to potentially inappropriate prescribing in older primary care
outpatients (>=65 years). METHODS: Two separate, age- and sex-matched case
control studies were carried out simultaneously at the Primary Health Care Center
Kragujevac, Serbia, during the period September 2013-September 2014. The cases
were defined as patients with at least one prescription for potentially
inappropriate medication (PIM) according to Screening Tool of Older Persons
potentially inappropriate Prescriptions (STOPP) criteria (n = 122), and patients
who had at least one potential prescribing omission (PPO) listed in Screening
Tool to Alert doctors to the Right Treatment (START) criteria (n = 108), while
the control groups consisted of patients without such outcomes (n = 244 and n =
216, respectively). RESULTS: A total of 138 PIM and 161 PPO events were
identified using 26 (41.3 %) of STOPP criteria and 17 (77.3 %) of START
indicators, respectively. The unhealthy behaviors including at least two of the
following: sedentary lifestyle, improper nutrition, active smoking or heavy
alcohol consumption (adjusted OR 2.57, 95 % CI 1.28-5.20), use of multiple drugs
(five to eight drugs, adjusted OR 3.05, 95 % CI 1.59-5.85; >=9 of drugs adjusted
OR 7.17, 95 % CI 3.07-16.74) and frequent contacts between patients chosen
general practitioners (GPs) and pharmaceutical sales representatives (adjusted OR
2.28, 95 % CI 1.10-4.75), were identified as major risk factors for PIM use.
Patients who were handled by GPs from smaller practices (adjusted OR 0.51, 95 %
CI 0.29-0.93), those with more organ systems affected by the extremely severe
disorders and those who often visited the outpatient specialist services
(adjusted OR 0.88, 95 % CI 0.81-0.95), had a significantly reduced risk of PPO.
CONCLUSIONS: This study suggests that avoidance of major polypharmacy, use of
nonpharmacological measures to improve lifestyle habits and decreasing the
exposure of physicians to drug promotional material may reduce the risk of PIM
use in older primary care outpatients. The only modifiable protective factors for
PPOs were working environment of the patients chosen GPs and more frequent
ambulatory visits to specialists.
PMID- 26416102
TI - Optimizing Intradermal Administration of Cryopreserved Plasmodium falciparum
Sporozoites in Controlled Human Malaria Infection.
AB - Controlled human malaria infection (CHMI) is a powerful tool to evaluate malaria
vaccine and prophylactic drug efficacy. Until recently CHMI was only carried out
by the bite of infected mosquitoes. A parenteral method of CHMI would standardize
Plasmodium falciparum sporozoite (PfSPZ) administration, eliminate the need for
expensive challenge facility infrastructure, and allow for use of many P.
falciparum strains. Recently, intradermal (ID) injection of aseptic, purified,
cryopreserved PfSPZ was shown to induce P. falciparum malaria; however, 100%
infection rates were not achieved by ID injection. To optimize ID PfSPZ dosing so
as to achieve 100% infection, 30 adults aged 18-45 years were randomized to one
of six groups composed of five volunteers each. The parameters of dose (1 * 10(4)
versus 5 * 10(4) PfSPZ total dose per volunteer), number of injections (two
versus eight), and aliquot volume per ID injection (10 MUL versus 50 MUL) were
studied. Three groups attained 100% infection: 1 * 10(4) PfSPZ in 50 MUL/2 doses,
1 * 10(4) PfSPZ in 10 MUL/2 doses, and 5 * 10(4) PfSPZ in 10 MUL/8 doses. The
group that received 5 * 10(4) PfSPZ total dose in eight 10 MUL injections had a
100% infection rate and the shortest prepatent period (mean of 12.7 days),
approaching the prepatent period for the current CHMI standard of five infected
mosquitoes.
PMID- 26416103
TI - Analysis of Risk and Burden of Dysentery Associated with Floods from 2004 to 2010
in Nanning, China.
AB - This study aimed to examine the association between floods and the morbidity of
dysentery and to quantify the burden of dysentery due to floods in Nanning,
China. A generalized additive mixed model was conducted to assess the
relationship between monthly morbidity of dysentery and floods from 2004 to 2010.
The years lived with disability (YLDs) of dysentery attributable to floods were
then estimated based on the WHO framework of the burden of disease study for
calculating the potential impact fraction. The relative risk (RR) of floods on
the morbidity of dysentery was 1.44 (95% confidence interval [CI] = 1.18-1.75).
The models suggest that a potential 1-day rise in flood duration may lead to 8%
(RR = 1.08, 95% CI = 1.04-1.12) increase in the morbidity of dysentery. The
average attributable YLD per 1,000 of dysentery caused by floods were 0.013 in
males, 0.005 in females, and 0.009 in persons. Our study confirms that floods
have significantly increased the risk and the burden of dysentery in the study
area. Public health action should be taken to prevent and control the potential
risk of dysentery after floods. Vulnerable groups such as males and children
should be paid more attention.
PMID- 26416104
TI - Pharmacokinetic Interactions Between Quinine and Lopinavir/Ritonavir in Healthy
Thai Adults.
AB - This study aimed to investigate the pharmacokinetic interactions between quinine
and lopinavir boosted with ritonavir (LPV/r) in healthy Thai adults (8 males and
12 females). Period 1 (day 1): subjects received a single oral dose of 600 mg
quinine sulfate. Period 2: subjects received LPV/r (400/100 mg) twice daily.
Period 3: subjects received a single quinine sulfate dose plus LPV/r twice a day.
Intensive blood sampling was performed during each phase. Quinine AUC0-48h (area
under the plasma concentration-time curve from time 0 to 48 hours), AUC0-infinity
(area under the plasma concentration-time curve from time 0 to infinity), and
Cmax (maximum concentration over the time-span specified), were 56%, 57%, and 47%
lower, respectively, in the presence of LPV/r. 3-Hydroxyquinine AUC0-48h, AUC0
infinity, and Cmax were significantly lower and the metabolite-to-parent ratio
was significantly reduced. Lopinavir and ritonavir exposures were not
significantly reduced with quinine coadministration, but Cmax of both drugs were
significantly lower. The geometric mean ratio (GMR) and 90% CI of AUC0-48h, AUC0
infinity, and Cmax for quinine, 3-hydroxyquinine, lopinavir, and ritonavir lay
outside the bioequivalent range of 0.8-1.25. Drug treatments during all periods
were generally well tolerated. The reduction in systemic exposure of quinine and
3-hydroxyquinine with concomitant LPV/r use raises concerns of suboptimal
exposure. Studies in HIV/malaria coinfection patients are needed to determine the
clinical impact to decide if any change to the quinine dose is warranted.
PMID- 26416105
TI - Rapid Tests and the Diagnosis of Visceral Leishmaniasis and Human
Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Coinfection.
AB - After the emergence of the human immunodeficiency virus (HIV)/acquired
immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis (VL)
HIV/AIDS coinfections has increased worldwide. Herein, we assessed the usefulness
of an rK39-based immunochromatographic test (rK39 ICT) (DiaMed-IT LEISH((r));
DiaMed AG, Cressier-sur-Morat, Switzerland) and a latex agglutination test
(KAtex; Kalon Biological, Guildford, United Kingdom) for urinary antigen
detection to diagnose VL in 15 HIV/AIDS patients from northeastern Brazil. VL
diagnosis was based on clinical findings, cytology, serology, parasite DNA,
and/or urinary antigen detection. VL was confirmed in seven out of 15 HIV/AIDS
patients. Only three patients were positive in bone marrow cytology, three
patients were conventional polymerase chain reaction (PCR) positive, while six
were real-time PCR positive. All patients were direct agglutination test (DAT)
(Royal Tropical Institute, Amsterdam, The Netherlands) positive; of these, four
were positive by rK39 ICT and five by KAtex. Large-scale studies are needed to
validate the use of the KAtex in the national public health laboratory network in
Brazil, aiming at improving the diagnosis of VL in HIV/AIDS patients in this
country.
PMID- 26416106
TI - Predictive Malaria Risk and Uncertainty Mapping in Nchelenge District, Zambia:
Evidence of Widespread, Persistent Risk and Implications for Targeted
Interventions.
AB - Malaria risk maps may be used to guide policy decisions on whether vector control
interventions should be targeted and, if so, where. Active surveillance for
malaria was conducted through household surveys in Nchelenge District, Zambia
from April 2012 through December 2014. Households were enumerated based on
satellite imagery and randomly selected for study enrollment. At each visit,
participants were administered a questionnaire and a malaria rapid diagnostic
test (RDT). Logistic regression models were used to construct spatial prediction
risk maps and maps of risk uncertainty. A total of 461 households were visited,
comprising 1,725 participants, of whom 48% were RDT positive. Several
environmental features were associated with increased household malaria risk in a
multivariable logistic regression model adjusting for seasonal variation. The
model was validated using both internal and external evaluation measures to
generate and assess root mean square error, as well as sensitivity and
specificity for predicted risk. The final, validated model was used to predict
and map malaria risk including a measure of risk uncertainty. Malaria risk in a
high, perennial transmission setting is widespread but heterogeneous at a local
scale, with seasonal variation. Targeting malaria control interventions may not
be appropriate in this epidemiological setting.
PMID- 26416107
TI - Investigating a Non-Mesh Mosquito Net Among Outdoor Sleeping Nomadic Communities
in Kenya.
AB - Rising reports of exophagic malaria vectors make even more pressing the need for
alternatives to traditional, mesh, long-lasting insecticidal nets (LLINs)
designed for indoor sleeping and often inadequate in the protection of outdoor
sleeping populations. This study tests and evaluates the retention, utilization,
and durability of novel, non-mesh nets designed for outdoor use. Longitudinal,
cross-sectional surveys were conducted, the physical condition of nets was
assessed, and bio-efficacy and insecticide content were tested. At 22 months,
retention was 98.0%; 97.1% of nets fell within the World Health Organization
(WHO) category of being in "good" condition; none were in the "torn" category. At
18 months post-distribution, 100% of nets had at least WHO Pesticide Evaluation
Scheme (WHOPES)-acceptable levels of insecticide, this proportion was 66.7% at 22
months. This novel mosquito net has the potential to provide a durable and
context-specific tool to prevent malaria among traditionally hard-to-protect and
highly vulnerable populations.
PMID- 26416108
TI - Predictive Value of School-Aged Children's Schistosomiasis Prevalence and Egg
Intensity for Other Age Groups in Western Kenya.
AB - World Health Organization recommendations for the timing and target population
for mass drug administration (MDA) for schistosomiasis are based on the
prevalence of infection in school children within a given community. In a large
study comparing MDA approaches for Schistosoma mansoni control, we evaluated
whether prevalence of infection and egg burdens in 9- to 12-year-old students
reflected infection levels in young children and adults in the same community.
Cross-sectional surveys of preadolescents (9-12 years old) were compared with
those of first year students (5-8 years old) in 225 villages and adults (20-55
years old) in 150 villages along the Kenyan shores of Lake Victoria. Village
schistosomiasis prevalence and intensity levels in preadolescents strongly
correlated (P < 0.0001) with prevalence and infection intensity for other age
groups in the community. Our findings suggest that S. mansoni prevalence and
intensity among 9- to 12-year-olds are valid for community sampling purposes in
mapping for MDAs.
PMID- 26416109
TI - Chikungunya Virus Infections Among Patients with Dengue-Like Illness at a
Tertiary Care Hospital in the Philippines, 2012-2013.
AB - Chikungunya virus (CHIKV) often co-circulates with dengue virus (DENV). A cross
sectional surveillance study was conducted at a tertiary hospital in Manila,
Philippines, to describe the prevalence and characteristics of DENV and CHIKV
infections among patients seeking care for dengue-like illness. Acute blood
samples from patients >= 6 months of age clinically diagnosed with dengue from
November 2012 to December 2013 underwent reverse transcription polymerase chain
reaction (RT-PCR) to detect DENV and CHIKV RNA. A total of 118 patients with
clinically diagnosed dengue (age range = 1-89 years, mean = 22 years; male-to
female ratio = 1.51) were tested by DENV RT-PCR; 40 (34%) were DENV PCR-positive
(age range = 1-45 years, mean = 17 years). All DENV serotypes were detected: 11
(28%) DENV-1, 6 (15%) DENV-2, 6 (15%) DENV-3, and 17 (42%) DENV-4. Of 112
patients clinically diagnosed with dengue and tested by CHIKV RT-PCR, 11 (10%)
were CHIKV PCR-positive (age range = 2-47 years, mean = 20.3 years). No
coinfections were detected. Presenting signs/symptoms did not differ between DENV
and CHIKV-positive cases. Sequencing of envelope 1 gene from two CHIKV PCR
positive samples showed Asian genotype. This study highlights the potential for
misdiagnosis of medically attended CHIKV infections as DENV infection and the
difficulty in clinically differentiating dengue and chikungunya based on
presenting signs/symptoms alone. This underscores the necessity for diagnostic
laboratory tests to distinguish CHIKV infections in the background of actively co
circulating DENV.
PMID- 26416110
TI - Deforestation and Malaria on the Amazon Frontier: Larval Clustering of Anopheles
darlingi (Diptera: Culicidae) Determines Focal Distribution of Malaria.
AB - We performed bimonthly mosquito larval collections during 1 year, in an
agricultural settlement in the Brazilian Amazon, as well as an analysis of
malaria incidence in neighboring houses. Water collections located at forest
fringes were more commonly positive for Anopheles darlingi larvae and Kulldorff
spatial analysis pinpointed significant larval clusters at sites directly beneath
forest fringes, which were called larval "hotspots." Remote sensing identified 43
"potential" hotspots. Sampling of these areas revealed an 85.7% positivity rate
for A. darlingi larvae. Malaria was correlated with shorter distances to
potential hotpots and settlers living within 400 m of potential hotspots had a
2.60 higher risk of malaria. Recently arrived settlers, usually located closer to
the tip of the triangularly shaped deforestation imprints of side roads, may be
more exposed to malaria due to their proximity to the forest fringe. As
deforestation progresses, transmission decreases. However, forest remnants inside
deforested areas conferred an increased risk of malaria. We propose a model for
explaining frontier malaria in the Amazon: because of adaptation of A. darlingi
to the forest fringe ecotone, humans are exposed to an increased transmission
risk when in proximity to these areas, especially when small dams are created on
naturally running water collections.
PMID- 26416112
TI - Feasibility of Using the Mosquito Blood Meal for Rapid and Efficient Human and
Animal Virus Surveillance and Discovery.
AB - Mosquito blood meals taken from humans and animals potentially represent a useful
source of blood for the detection of blood-borne pathogens. In this feasibility
study, Anopheles stephensi mosquitoes were fed with blood meals spiked with
dengue virus type 2 (DENV-2) and harvested at serial time points. These
mosquitoes are not competent vectors, and the virus is not expected to replicate.
Ingested blood was spotted on Whatman FTA cards and stored at room temperature.
Mosquito abdomens were removed and stored at -80 degrees C. Control blood meal
aliquots were stored in vials or applied onto FTA cards. After 4 weeks of
storage, the samples were extracted using beadbeating and QIAamp Viral RNA kit
(Qiagen Sciences, Germantown, MD). Recovered viral RNA was analyzed by DENV-2
TaqMan RT-PCR assay and next-generation sequencing (NGS). Overall viral RNA
recovery efficiency was 15% from the directly applied dried blood spots and
approximately 20% or higher for dried blood spots made by blotting mosquito
midgut on FTA cards. Viral RNA in mosquito-ingested blood decreases over time,
but remains detectable 24 hours after blood feeding. The viral sequences in FTA
stored specimens can be maintained at room temperature. The strategy has the
potential utility in expedited zoonotic virus discovery and blood-borne pathogen
surveillance.
PMID- 26416111
TI - Point-of-Care Ultrasound Assessment of Tropical Infectious Diseases--A Review of
Applications and Perspectives.
AB - The development of good quality and affordable ultrasound machines has led to the
establishment and implementation of numerous point-of-care ultrasound (POCUS)
protocols in various medical disciplines. POCUS for major infectious diseases
endemic in tropical regions has received less attention, despite its likely even
more pronounced benefit for populations with limited access to imaging
infrastructure. Focused assessment with sonography for HIV-associated TB (FASH)
and echinococcosis (FASE) are the only two POCUS protocols for tropical
infectious diseases, which have been formally investigated and which have been
implemented in routine patient care today. This review collates the available
evidence for FASH and FASE, and discusses sonographic experiences reported for
urinary and intestinal schistosomiasis, lymphatic filariasis, viral hemorrhagic
fevers, amebic liver abscess, and visceral leishmaniasis. Potential POCUS
protocols are suggested and technical as well as training aspects in the context
of resource-limited settings are reviewed. Using the focused approach for
tropical infectious diseases will make ultrasound diagnosis available to patients
who would otherwise have very limited or no access to medical imaging.
PMID- 26416113
TI - First Report of Aedes aegypti Transmission of Chikungunya Virus in the Americas.
AB - During a chikungunya fever outbreak in late 2014 in Chiapas, Mexico,
entomovirological surveillance was performed to incriminate the vector(s). In
neighborhoods, 75 households with suspected cases were sampled for mosquitoes, of
which 80% (60) harbored Aedes aegypti and 2.7% (2) Aedes albopictus. A total of
1,170 Ae. aegypti and three Ae. albopictus was collected and 81 pools were
generated. Although none of the Ae. albopictus pools were chikungunya virus
(CHIKV)-positive, 18 Ae. aegypti pools (22.8%) contained CHIKV, yielding an
infection rate of 32.3/1,000 mosquitoes. A lack of herd immunity in conjunction
with high mosquito populations, poor vector control services in this region, and
targeted collections in locations of human cases may explain the high infection
rate in this vector. Consistent with predictions from experimental studies, Ae.
aegypti appears to be the principal vector of CHIKV in southern Mexico, while the
role of Ae. albopictus remains unknown.
PMID- 26416114
TI - Challenges in Obtaining Estimates of the Risk of Tuberculosis Infection During
Overseas Deployment.
AB - Estimates of the risk of tuberculosis (TB) infection resulting from overseas
deployment among U.S. military service members have varied widely, and have been
plagued by methodological problems. The purpose of this study was to estimate the
incidence of TB infection in the U.S. military resulting from deployment. Three
populations were examined: 1) a unit of 2,228 soldiers redeploying from Iraq in
2008, 2) a cohort of 1,978 soldiers followed up over 5 years after basic training
at Fort Jackson in 2009, and 3) 6,062 participants in the 2011-2012 National
Health and Nutrition Examination Survey (NHANES). The risk of TB infection in the
deployed population was low-0.6% (95% confidence interval [CI]: 0.1-2.3%)-and was
similar to the non-deployed population. The prevalence of latent TB infection
(LTBI) in the U.S. population was not significantly different among deployed and
non-deployed veterans and those with no military service. The limitations of
these retrospective studies highlight the challenge in obtaining valid estimates
of risk using retrospective data and the need for a more definitive study.
Similar to civilian long-term travelers, risks for TB infection during deployment
are focal in nature, and testing should be targeted to only those at increased
risk.
PMID- 26416115
TI - An Unusual Cutaneous Manifestation in a Patient with Murine Typhus.
AB - Murine typhus is a flea-borne febrile illness caused by Rickettsia typhi.
Although often accompanied by rash, an inoculation lesion has not been observed
as it is with many tick- and mite-transmitted rickettsioses. We describe a
patient with murine typhus and an unusual cutaneous manifestation at the site of
rickettsial inoculation.
PMID- 26416116
TI - Cost of Dengue Vector Control Activities in Malaysia.
AB - Dengue fever, an arbovirus disease transmitted by Aedes mosquitoes, has recently
spread rapidly, especially in the tropical countries of the Americas and Asia
Pacific regions. It is endemic in Malaysia, with an annual average of 37,937
reported dengue cases from 2007 to 2012. This study measured the overall economic
impact of dengue in Malaysia, and estimated the costs of dengue prevention. In
2010, Malaysia spent US$73.5 million or 0.03% of the country's GDP on its
National Dengue Vector Control Program. This spending represented US$1,591 per
reported dengue case and US$2.68 per capita population. Most (92.2%) of this
spending occurred in districts, primarily for fogging. A previous paper estimated
the annual cost of dengue illness in the country at US$102.2 million. Thus, the
inclusion of preventive activities increases the substantial estimated cost of
dengue to US$175.7 million, or 72% above illness costs alone. If innovative
technologies for dengue vector control prove efficacious, and a dengue vaccine
was introduced, substantial existing spending could be rechanneled to fund them.
PMID- 26416117
TI - Blood-Borne Candidatus Borrelia algerica in a Patient with Prolonged Fever in
Oran, Algeria.
AB - To improve the knowledge base of Borrelia in north Africa, we tested 257 blood
samples collected from febrile patients in Oran, Algeria, between January and
December 2012 for Borrelia species using flagellin gene polymerase chain reaction
sequencing. A sequence indicative of a new Borrelia sp. named Candidatus Borrelia
algerica was detected in one blood sample. Further multispacer sequence typing
indicated this Borrelia sp. had 97% similarity with Borrelia crocidurae, Borrelia
duttonii, and Borrelia recurrentis. In silico comparison of Candidatus B.
algerica spacer sequences with those of Borrelia hispanica and Borrelia garinii
revealed 94% and 89% similarity, respectively. Candidatus B. algerica is a new
relapsing fever Borrelia sp. detected in Oran. Further studies may help predict
its epidemiological importance.
PMID- 26416118
TI - Effectiveness of Large-Scale Chagas Disease Vector Control Program in Nicaragua
by Residual Insecticide Spraying Against Triatoma dimidiata.
AB - Chagas disease is one of the most serious health problems in Latin America.
Because the disease is transmitted mainly by triatomine vectors, a three-phase
vector control strategy was used to reduce its vector-borne transmission. In
Nicaragua, we implemented an indoor insecticide spraying program in five northern
departments to reduce house infestation by Triatoma dimidiata. The spraying
program was performed in two rounds. After each round, we conducted entomological
evaluation to compare the vector infestation level before and after spraying. A
total of 66,200 and 44,683 houses were sprayed in the first and second spraying
rounds, respectively. The entomological evaluation showed that the proportion of
houses infested by T. dimidiata was reduced from 17.0% to 3.0% after the first
spraying, which was statistically significant (P < 0.0001). However, the second
spraying round did not demonstrate clear effectiveness. Space-time analysis
revealed that reinfestation of T. dimidiata is more likely to occur in clusters
where the pre-spray infestation level is high. Here we discuss how large-scale
insecticide spraying is neither effective nor affordable when T. dimidiata is
widely distributed at low infestation levels. Further challenges involve research
on T. dimidiata reinfestation, diversification of vector control strategies, and
implementation of sustainable vector surveillance.
PMID- 26416119
TI - Three-dimensional kinematic analysis of ankle, knee, hip, and pelvic rotation
during gait in patients after anterior cruciate ligament reconstruction - early
results.
AB - BACKGROUND: The goal of this study was to biomechanically assess tibial rotation
in the knee joint simultaneous changes in rotation of large joints of the lower
limbs and pelvis during gait in patients during early postoperative stages
following anterior cruciate ligament (ACLR) reconstruction. We hypothesized that
tibial rotation is associated with changes in rotation of the large joints of the
lower limbs and the pelvis during gait in patients after ACLR reconstruction.
METHODS: The patients were divided into two groups. The ACLR group (n = 32 males)
underwent primary ACLR in one leg and postoperative physiotherapy. The control
group (n = 30 males) had no knee injuries. After clinical assessment in both
groups, the values of kinematic parameters of foot, tibial, femoral, and pelvic
rotation were measured during gait on a flat surface using the three-dimensional
BTS Smart System. In the ACLR group, measurements were taken during the 4th, 9th,
and 14th weeks of postoperative physiotherapy. The results of the ACLR group were
compared with those of the control group. RESULTS: During gait, between the 9th
and 14th weeks following ACLR, there are normal values of foot, tibia, and pelvic
rotation in the operated legs compared with results obtained from un-operated
legs and the control group. DISCUSSION: Analysis of rotations occurring only in
knee joints does not reflect all of the multiarticular disorders of gait
kinematics. The study also suggests that analyzing tibial rotation in the knee
joint with simultaneous changes in rotation in large joints of the lower limbs
provides better opportunities than singular analysis of rotation in the knee
joint for the assessment of disorders in gait kinematics. CONCLUSIONS: In gait,
at the maximal extension of the knee during preparation for the stance phase,
external hip rotation patterns have not been fully restored 14 weeks after ACLR.
PMID- 26416120
TI - Preanesthetic nurse communication with children and parents--an observational
study.
AB - BACKGROUND: The impact of communication within the perioperative period is an
area of increasing research interest. Suggestions are phrases or actions that can
lead to subconscious nonvolitional changes in patient perception, mood, and/or
behavior. Statements functioning as suggestions may induce positive or negative
perceptual responses and experiences. Children and anxious patients are
particularly responsive to the effects of suggestion. We aimed to identify
positively and negatively worded statements used during the provision of
preoperative information by nursing staff in a tertiary referral center for
pediatric care. METHODS: Audio recordings of preoperative consultations between
nurses, children, and their parents were made between February and May 2014. Two
researchers independently reviewed the transcripts and identified positively and
negatively worded suggestions. Examples of negative suggestions were, 'he is
going to be sore for a week or two' or 'normal to feel a bit sick....', and a
positive suggestion was 'so she will be feeling quite comfortable...'. RESULTS:
There were 51 consultations transcribed and analyzed. Of the 130 suggestions
independently agreed by both researchers to be either positive or negative, 40
were identified as positive (31%) and 90 negative (69%). Commonly occurring
negative suggestions described: pain in 21 consultations (41%); nausea and
sickness in 19 (37%); and irritability or agitation in nine (18%). Positive
suggestions included a description of a return of normal activities such as
eating and drinking in 14 (28%), comfort in nine (18%), and well-being in nine
(18%). Twelve consultations (24%) contained only negative suggestions, while four
(8%) had only positive suggestions. CONCLUSIONS: This is the first prospective
observational study investigating the language used by nurses during the
preoperative child-parent encounter. Suggestions for negative perceptual
experiences were frequently used during the preoperative nurse consultations.
Education of nurses regarding awareness and understanding of negative suggestions
and their potential adverse effects is recommended.
PMID- 26416121
TI - Salt stress-induced modulations in the shoot proteome of Brassica juncea
genotypes.
AB - Indian mustard [Brassica juncea (L.) Czern and Coss] is cultivated mainly in the
northwestern agroclimatic region of India and suffers huge losses in productivity
due to salinization. In an effort to figure out adaptation strategies of Indian
mustard to salt stress, we conducted a comparative proteome analysis of shoots of
its two genotypes, with contrasting sensitivity to salt stress. Differential
expression of 21 proteins was observed during the two-dimensional electrophoresis
(2DE). The identified salt-stress-responsive proteins were associated with
different functional processes including osmoregulation, photosynthesis,
carbohydrate metabolism, ion homeostasis, protein synthesis and stabilization,
energy metabolism, and antioxidant defense system. Salt-tolerant genotype (CS-52)
showed a relatively higher expression of proteins involved in turgor regulation,
stabilization of photosystems and proteins, and salt compartmentalization, as
compared to salt-sensitive genotype (Pusa Varuna). Our results suggest that
modulating the expression of salt-responsive proteins can pave the way for
developing salt tolerance in the Indian mustard plants.
PMID- 26416122
TI - Effect of chemo-mechanical disintegration on sludge anaerobic digestion for
enhanced biogas production.
AB - The effect of combined surfactant-dispersion pretreatment on dairy waste
activated sludge (WAS) reduction in anaerobic digesters was investigated. The
experiments were performed with surfactant, Sodium dodecyl sulfate (SDS) in the
range of 0.01 to 0.1 g/g suspended solids (SS) and disperser with rpm of 5000
25,000. The COD (chemical oxygen demand) solubilization, suspended solids
reduction, and biogas generation increased for an energy input of 7377 kJ/kg
total solids (TS) (12,000 rpm, 0.04 g/g SS, and 30 min) and were found to be 38,
32, and 75 %, higher than that of control. The pretreated sludge improved the
performance of semicontinuous anaerobic digesters of 4 L working volume operated
at four different SRTs (sludge retention time). SRT of 15 days was found to be
appropriate showing 49 and 51 % reduction in SS and volatile solids (VS),
respectively. The methane yield of the pretreated sample was observed to be 50
mL/g VS removed which was observed to be comparatively higher than the control
(12 mL/g VS removed) at optimal SRT of 15 days. To the best of the authors'
knowledge, this study is the first to be reported and not yet been documented in
literature.
PMID- 26416123
TI - Iron and copper catalysis of PCDD/F formation.
AB - The formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) was
explored during de novo tests designed to compare the catalytic activity of
copper (II) chloride (CuCl2) with that of iron (III) oxide (Fe2O3) and to test
some synergistic effect between these two catalytic compounds. Both copper
chloride (CuCl2) and iron oxide (Fe2O3) were earlier proposed as catalysts to
explain the PCDD/F emissions from, e.g. municipal solid waste incineration
(MSWI). In addition, haematite (Fe2O3) is the main iron ore and could be
responsible for the typical iron ore sintering plant fingerprint. A total of nine
model fly ash (MFA) samples were prepared by mixing and grinding of sodium
chloride (NaCl), activated carbon and a powder matrix of silica (SiO2) with the
selected metal compound(s). The conditions of these de novo tests were 1 h in
duration, 350 degrees C in a flow of synthetic combustion gas (10 vol.% oxygen
in nitrogen). The effect of Fe-Cu catalyst concentration on yield and
distribution pattern of PCDD/F was systematically explored; three strongly
differing ratios of [Fe]:[Cu] were considered (1:1, 10:1 and 100:1) to study the
potential interactions of Fe2O3 and CuCl2 suggested earlier. The results show
some slight rise of PCDD/F formed with raising iron concentration from 0 to 10.1
wt% (no Cu added; 0.1 wt% Cu), as well as strong surging of both amount and
average chlorination level of PCDD/F when rising amounts of copper (0 to 1.1 wt%)
are introduced. The resulting fingerprints are compared with those from sintering
and from MSWI.
PMID- 26416124
TI - Simulation of aromatic polycyclic hydrocarbons remobilization from a river
sediment using laboratory experiments supported by passive sampling techniques.
AB - Resuspension of bedded sediments was simulated under laboratory-controlled
conditions in order to assess the amount of polycyclic aromatic hydrocarbons
(PAH) remobilized in the dissolved fraction during one short and vigorous mixing.
The desorbed amount of PAH was compared to the exchangeable fraction, the total
amount of PAH sorbed on the sediment particles, and the dissolved PAH amount
contained in the interstitial pore waters in order to evaluate the contribution
of each fraction to the total amount of PAH released. To monitor the desorption
of PAH and measure low trace level concentrations, passive samplers were used in
an experimental open flow through exposure simulator. Results show that for the
selected sediment, a substantial fraction of sorbed PAH (69 % of the total
amount) is not available for remobilization in a depleted medium. Obtained data
pinpoint that over 9 days, only 0.007 % of PAH are desorbed by passive diffusion
through a water-sediment interface area of 415 cm(2) and that an intense
resuspension event of 15 min induces desorption of 0.015 % of PAH during the
following 9 days. Results also highlight that during resuspension simulation,
modifications of the sediment and the water body occurred since partitioning
constants of some pollutants between sediment and water have significantly
decreased.
PMID- 26416126
TI - Erratum to: Disentangling Multiple Sclerosis and depression: an adjusted
depression screening score for patient-centered care.
PMID- 26416125
TI - beta-aminobutyric acid mediated drought stress alleviation in maize (Zea mays
L.).
AB - The present study highlights the role of beta-aminobutyric acid (BABA) in
alleviating drought stress effects in maize (Zea mays L.). Chemical priming was
imposed by pretreating 1-week-old plants with 600 MUM BABA prior to applying
drought stress. Specific activities of key antioxidant enzymes and metabolites
(ascorbate and glutathione) levels of ascorbate-glutathione cycle were studied to
unravel the priming-induced modulation of plant defense system. Furthermore,
changes in endogenous ABA and JA concentrations as well as mRNA expressions of
key genes involved in their respective biosynthesis pathways were monitored in
BABA-primed (BABA+) and non-primed (BABA-) leaves of drought-challenged plants to
better understand the mechanistic insights into the BABA-induced hormonal
regulation of plant response to water-deficit stress. Accelerated stomatal
closure, high relative water content, and less membrane damage were observed in
BABA-primed leaves under water-deficit condition. Elevated APX and SOD activity
in non-primed leaves found to be insufficient to scavenge all H2O2 and O2 (.-)
resulting in oxidative burst as evident after histochemical staining with NBT and
DAB. A higher proline accumulation in non-primed leaves also does not give much
protection against drought stress. Increased GR activity supported with the
enhanced mRNA and protein expressions might help the BABA-primed plants to
maintain a high GSH pool essential for sustaining balanced redox status to
counter drought-induced oxidative stress damages. Hormonal analysis suggests that
in maize, BABA-potentiated drought tolerance is primarily mediated through JA
dependent pathway by the activation of antioxidant defense systems while ABA
biosynthesis pathway also plays an important role in fine-tuning of drought
stress response.
PMID- 26416128
TI - Protein Aggregates May Differ in Water Entrapment but Are Comparable in Water
Confinement.
AB - Aggregate size and density are related to gel morphology. In the context of the
water distribution in complex food systems, in this study, it was aimed to
investigate whether protein aggregates varying in size and density differ in
entrapped and confined water. Heat-set soy protein aggregates (1%, v/v) prepared
in the presence of 3.5 mM divalent salts increased in size and decreased in
apparent density following the salt type order MgSO4, MgCl2, CaSO4, and CaCl2. In
the absence of applied (centrifugal) forces, larger and less dense aggregates
entrap more water. When force is applied from larger and more deformable
aggregates, more water can be displaced. Entrapped water of ~8-13 g of water/g of
protein is associated with (pelleted) aggregates, of which approximately 4.5-8.5
g of water/g of protein is not constrained in exchangeability with the solvent.
The amount of confined water within aggregates was found to be independent of the
aggregate density and accounted for ~3.5 g of water/g of protein. Confined water
in aggregates is hindered in its diffusion because of physical structure
constraints and, therefore, not directly exchangeable with the solvent. These
insights in the protein aggregate size and deformability in relation to water
entrapment and confinement could be used to tune water holding on larger length
scales when force is applied.
PMID- 26416127
TI - Mammography Adherence in African-American Women: Results of a Randomized
Controlled Trial.
AB - BACKGROUND: Breast cancer is the second leading cause of cancer mortality among
women in the developed world. Mammography screening is especially important for
African-Americans because they experience a greater mortality (OR = 1.38) than
Caucasians despite having a lower incidence of breast cancer. PURPOSE: The
purpose of this study was to compare the effects of two interventions with usual
care on mammography adherence among African-American women. METHODS: A subsample
of African-American women (n = 244) aged 41-65 years who had not had a mammogram
in the last 15 months and no history of breast cancer was randomly assigned to
receive (1) mailed interactive DVD, (2) computer-tailored telephone counseling,
or (3) usual care. RESULTS: The DVD intervention was five times more effective
than usual care for promoting mammography screening at 6 months follow-up among
women who earned less than $30,000 (OR = 5.3). Compared to usual care, neither
the DVD nor phone produced significant effects for women with household incomes
>$30,000. CONCLUSION: Use of a mailed DVD for low-income African-American women
may be an effective way to increase mammography adherence.
PMID- 26416129
TI - Intubation of the Neurologically Injured Patient.
AB - BACKGROUND: Intubation of the neurologically injured patient is a critical
procedure that must be done in a manner to prevent further neurologic injury.
Although many different medications and techniques have been used to meet
specific needs, there is little to no evidence to support many claims. OBJECTIVE:
To review the literature regarding important topics relating to intubating
patients with neurologic injury. DISCUSSION: Airway management requires ideal
preoxygenation and airway maneuvers to minimize manipulation of the larynx and to
maximize first-pass success. There is no evidence that lidocaine pretreatment
decreases intracerebral pressure (ICP). Fentanyl can be used to help blunt the
hemodynamic response to intubation. Esmolol is another medication that can blunt
the hemodynamic response. Ketamine can be used and is possibly the ideal agent,
having a neutral hemodynamic profile. A prefasciculation dose for neuromuscular
blockade has not been shown to have any effect on ICP. CONCLUSIONS: Ideal
intubation conditions should be obtained through the use of airway manipulation
techniques and appropriate medication choice for rapid sequence intubation in
patients who are neurologically injured.
PMID- 26416130
TI - Septal Hematoma Following Nasal Trauma.
PMID- 26416131
TI - Hypothermia-induced Rhabdomyolysis: A Case Report.
AB - BACKGROUND: A 29-year-old man was lost in the bush with minimal clothing for
almost 2 days. CASE REPORT: The patient in this case developed rhabdomyolysis
with subsequent acute kidney injury. He was treated with passive warming and
intravenous fluids, with resolution of the kidney injury. WHY SHOULD AN EMERGENCY
PHYSICIAN BE AWARE OF THIS?: Patients who present with hypothermia may develop
rhabdomyolysis with subsequent acute kidney injury. If not identified, renal
failure may develop. This is easily preventable if the practitioner is aware of
the possible consequences of cold exposure, orders the appropriate test, and
administers corrective treatment.
PMID- 26416132
TI - Use of Proteolytic Enzymes in the Treatment of Proteinaceous Esophageal Food
Impaction.
AB - BACKGROUND: Proteinaceous esophageal food impaction typically requires endoscopic
intervention. An alternative approach is the use of proteolytic enzymes. Concerns
regarding the use of proteolytic enzymes include the risk of perforation and
aspiration pneumonitis. OBJECTIVE: We retrospectively reviewed our series of 69
patients treated with papain to determine the safety and efficacy of proteolytic
enzymes. METHODS: Patients were retrospectively reviewed if treated for an
esophageal food impaction from 1999 through 2008. RESULTS: Median age was 56
years (range 19-91 years), with 46 male and 23 female patients. In 27 patients
(39%) this was their first presentation, in 14 (20%) it was the second, and 28
(41%) had multiple previous episodes. Meat was the cause in 49 (71%), chicken in
6 (9%), fish in 3 (4%), and unspecified in 11 (16%). All patients presented with
dysphagia for solids, 56 (81%) could not tolerate liquids. Papain solution, 1 tsp
in 8 oz of water, was given to patients in an unlimited quantity. Papain was
successful in relieving the obstruction in 60 patients (87%). The remaining 9
patients (13%) underwent endoscopy with successful retrieval. No patient suffered
a perforation, either with papain ingestion or endoscopy. There were no episodes
of pneumonitis or pneumonia. CONCLUSIONS: We have used proteolytic enzymes with a
high success rate and with minimal complication. Further, if proteolytic enzymes
fail, endoscopy can be performed safely and effectively. We recommend the use of
proteolytic enzymes as the initial management in all patients with proteinaceous
food impaction of the esophagus.
PMID- 26416133
TI - Impact of Age on Pain Perception for Typical Painful Diagnoses in the Emergency
Department.
AB - BACKGROUND: Age-related differences in pain perception have been demonstrated in
experimental settings but have been investigated scarcely and without valid scale
in the clinical framework. OBJECTIVES: To examine the effect of age on pain
perception for recognized painful diagnoses encountered in the emergency
department (ED). METHODS: A post-hoc analysis of real-time archived data was
performed in a tertiary urban and a secondary regional ED. We included all
consecutive adult patients (>=18 years) with the following diagnosis at
discharge: renal colic, pancreatitis, appendicitis, headache/migraine,
dislocation and extremities fractures, and a pain evaluation of >=1 (0-10, verbal
numerical scale) at triage. The primary outcome was to compare for each of these
diagnoses the level of pain intensity between four age groups (18-44; 45-64; 65
74; 75+ years). RESULTS: A total of 15,670 patients (48% women) were triaged with
a mean pain intensity of 7.7 (SD=2.0). Women exhibited greater pain scores than
men for pancreatitis, headache/migraine, and extremity fracture. Renal colic,
pancreatitis, appendicitis, and headache/migraine showed a linear decrease in
pain scores with age whereas dislocation and extremity fractures did not present
age differences. Mean differences in pain intensity scores between young adults
(18-44 years) and patients aged >=75 years were 0.79 (95% confidence interval
[95% CI] 0.5-1.1) for renal colic, 1.1 (95% CI 0.7-1.4) for pancreatitis, 0.70
(95% CI 0.2-1.2) for appendicitis, and 0.86 (95% CI 0.6-1.1) for
headache/migraine. CONCLUSION: Older patients perceive similar pain for
dislocation and extremity fractures and less for visceral and headache/migraine
pain; however, these age differences may not be clinically important.
PMID- 26416134
TI - Moxifloxacin Use and Its Association on the Diagnosis of Pulmonary Tuberculosis
in An Inner City Emergency Department.
AB - BACKGROUND: Moxifloxacin can be used in the treatment of tuberculosis, its effect
on the diagnosis and treatment of pulmonary tuberculosis is not well
characterized. OBJECTIVE: To identify patients from the St. Paul's Hospital
emergency department (ED) treated with moxifloxacin who also had sputum sent for
investigation of possible tuberculosis and the impact on sensitivity of acid-fast
bacilli (AFB) smears and time to initiation of tuberculosis treatment. METHODS:
We conducted a retrospective single-center cohort study on patients that were
prescribed moxifloxacin in the ED during a 5-year period and had samples
collected for pulmonary tuberculosis. All AFB samples obtained throughout the
hospital in patients not exposed to moxifloxacin during the same time period were
also examined. RESULTS: Two-thousand six hundred and seventy-three patients who
were admitted to St. Paul's Hospital through the ED received moxifloxacin during
the study period. 273 (10.2%) of these patients were subsequently investigated
for tuberculosis, with 9 positive cases of Mycobacterium tuberculosis (3.3%). One
thousand three hundred and sixty-nine patients not exposed to moxifloxacin were
screened for tuberculosis with 33 active cases (2.4%). The false-negative rate
for AFB smears in the exposed group was 85.2% vs. 53.8% in the unexposed group
(relative risk of false-negative AFB = 1.55; 95% CI 1.24-2.03). Time to
initiation of anti-tuberculosis therapy was significantly delayed in the exposed
group, with median time to initiation of 14 days vs. 2 days (p = 0.013).
CONCLUSIONS: Exposure to moxifloxacin is associated with significantly increased
rates of false-negative AFB smears and was associated with a significant delay in
the initiation of anti-tuberculosis therapy.
PMID- 26416135
TI - Race-related Healthcare Disparities Among California Workers: Public Health
Considerations for Immigration Reform.
AB - BACKGROUND: Healthcare disparities are prevalent in medicine and identifying them
will provide healthcare professionals, administrators, and policy makers needed
information to address this public health concern. OBJECTIVE: To evaluate racial
and ethnic disparities in the rates of hospital admission and death among
California workers. METHODS: We performed an analysis of hospital and emergency
department (ED) data from the Office of Statewide Health Planning and Development
(OSHPD). Data was collected from California licensed acute care hospitals from
2008-2010. INCLUSION CRITERIA: patients >15 years of age whose expected source of
payment was worker's compensation. EXCLUSION CRITERIA: patients <15 years; had
missing data for age, sex, race, or injury; or were injured by a suicide attempt,
poisoning, or complication of medical procedure. Multivariate logistic regression
was used to evaluate the relationship of race/ethnicity and admission/death
rates. RESULTS: There were 393,298 patients discharged from the ED and 23,343
patients admitted from ED had workers compensation as their expected sources of
payment and 150,277 met our inclusion criteria. The annual rate of ED treated
injuries was 209/100,000 for Caucasians 343/100,000 for Hispanics, 258/100,000
for blacks and 97/100,000 for Asians. Compared to Caucasians, admission odds
ratios (OR) were 1.15 (95% CI 1.07-1.25) for Hispanics, 1.08 (95% CI 0.87-1.33)
for blacks, and 0.78 (95% CI 0.63-0.97) for Asians. CONCLUSION: We observed race
and ethnicity related healthcare disparities among the occupationally injured in
California, with Hispanics having the highest odds of admission and annual
incidence of ED treated injuries. No difference in mortality rates was observed.
PMID- 26416136
TI - Spectrum of Extramammary Malignant Neoplasms in the Breast With Radiologic
Pathologic Correlation.
AB - Although primary breast cancer is the most common malignancy identified by breast
imaging, extramammary malignancies may also rarely be encountered. These uncommon
lesions may reflect primary neoplasms of nonmammary origin as well as secondary
metastatic lesions, and include lymphoma, melanoma, neuroendocrine tumors,
gastrointestinal tract malignancies, and angiosarcoma among other entities.
Malignant extramammary breast lesions may be encountered during routine
mammographic screening, identified during the diagnostic evaluation of a palpable
breast abnormality, or may be detected incidentally during imaging of other
organs of interest. As such, the radiologist should have familiarity with the
appearance of these lesions. This article focuses on a review of several of the
most common extramammary metastases to the breast, as well as a few lesions that
may develop as either primary or secondary lesions.
PMID- 26416137
TI - Introducing a short version of the Geneva Emotion Recognition Test (GERT-S):
Psychometric properties and construct validation.
AB - The ability to accurately interpret others' emotional expressions in the face,
voice, and body is a crucial component of successful social functioning and has
been shown to predict better outcomes in private and professional life. To date,
emotion recognition ability (ERA) has mostly been measured with tests that
heavily rely on static pictures of the face and on few emotions, restricting
their content validity. Recently, Schlegel, Grandjean, and Scherer (Psychological
Assessment, 26, 666-672, 2014) published a new test that measures ERA in a more
comprehensive fashion, by (1) including a wide range of 14 positive and negative
emotions and (2) using video clips with sound that simultaneously present facial,
vocal, and bodily emotional cues. This article introduces the short version of
the Geneva Emotion Recognition Test (the GERT-S), and presents two studies (total
N = 425) that examine the internal consistency, factor structure, and convergent
and discriminant validity of the test. The results show that the GERT-S is a
unidimensional test with good internal consistency. Furthermore, the GERT-S was
substantially positively correlated with other ERA tests, with tests of emotional
understanding and emotion management, and with cognitive ability. Taken together,
the present studies demonstrate the usefulness of the GERT-S as an instrument for
the brief and reliable assessment of ERA. It is available, free of charge and in
seven different languages, for academic research use. Given the brief test-taking
time (approx. 10 min) and its possible administration via different online
platforms, the GERT-S can easily be integrated by researchers into their own
studies.
PMID- 26416138
TI - The tool for the automatic analysis of text cohesion (TAACO): Automatic
assessment of local, global, and text cohesion.
AB - This study introduces the Tool for the Automatic Analysis of Cohesion (TAACO), a
freely available text analysis tool that is easy to use, works on most operating
systems (Windows, Mac, and Linux), is housed on a user's hard drive (rather than
having an Internet interface), allows for the batch processing of text files, and
incorporates over 150 classic and recently developed indices related to text
cohesion. The study validates TAACO by investigating how its indices related to
local, global, and overall text cohesion can predict expert judgments of text
coherence and essay quality. The findings of this study provide predictive
validation of TAACO and support the notion that expert judgments of text
coherence and quality are either negatively correlated or not predicted by local
and overall text cohesion indices, but are positively predicted by global indices
of cohesion. Combined, these findings provide supporting evidence that coherence
for expert raters is a property of global cohesion and not of local cohesion, and
that expert ratings of text quality are positively related to global cohesion.
PMID- 26416139
TI - Cortical network architecture for context processing in primate brain.
AB - Context is information linked to a situation that can guide behavior. In the
brain, context is encoded by sensory processing and can later be retrieved from
memory. How context is communicated within the cortical network in sensory and
mnemonic forms is unknown due to the lack of methods for high-resolution, brain
wide neuronal recording and analysis. Here, we report the comprehensive
architecture of a cortical network for context processing. Using hemisphere-wide,
high-density electrocorticography, we measured large-scale neuronal activity from
monkeys observing videos of agents interacting in situations with different
contexts. We extracted five context-related network structures including a bottom
up network during encoding and, seconds later, cue-dependent retrieval of the
same network with the opposite top-down connectivity. These findings show that
context is represented in the cortical network as distributed communication
structures with dynamic information flows. This study provides a general
methodology for recording and analyzing cortical network neuronal communication
during cognition.
PMID- 26416140
TI - AMPA receptor mediated synaptic excitation drives state-dependent bursting in
Purkinje neurons of zebrafish larvae.
AB - Purkinje neurons are central to cerebellar function and show membrane bistability
when recorded in vitro or in vivo under anesthesia. The existence of bistability
in vivo in awake animals is disputed. Here, by recording intracellularly from
Purkinje neurons in unanesthetized larval zebrafish (Danio rerio), we
unequivocally demonstrate bistability in these neurons. Tonic firing was seen in
depolarized regimes and bursting at hyperpolarized membrane potentials. In
addition, Purkinje neurons could switch from one state to another spontaneously
or with current injection. While GABAAR or NMDAR were not required for bursting,
activation of AMPARs by climbing fibers (CFs) was sufficient to trigger bursts.
Further, by recording Purkinje neuron membrane potential intracellularly, and
motor neuron spikes extracellularly, we show that initiation of motor neuron
spiking is correlated with increased incidence of CF EPSPs and membrane
depolarization. Developmentally, bistability was observed soon after Purkinje
neuron specification and persists at least until late larval stages.
PMID- 26416141
TI - Comment on Azmahani et al. "Steroidogenic enzymes, their related transcription
factors and nuclear receptors in human sebaceous glands under normal and
pathological conditions".
PMID- 26416142
TI - Assay reproducibility of serum androgen measurements using liquid chromatography
tandem mass spectrometry.
AB - BACKGROUND: Valid and precise measures of androgen concentrations are needed for
etiologic studies of hormonally-related cancers. We developed a high-performance
liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with two sample
preparations to measure 11 androgens, including adrenal and gonadal androgenic
precursors and their 5alpha-reduced metabolites. METHODS: Androgen levels were
measured in serum from 20 healthy volunteers (5 men, 10 premenopausal women, 5
postmenopausal women). Two blinded, randomized aliquots per individual were
assayed in each of three batches. A fourth batch of samples was measured at an
external laboratory using comparable methodology to measure 9 of the 11
androgens. Coefficients of variation (CV) and intraclass correlation coefficients
(ICC) were calculated from the individual components of variance. Comparability
of 9 androgens across laboratories was assessed using Spearman ranked
correlations, Deming regression and bias plots. RESULTS: The laboratory CVs were
<5% and ICCs were uniformly high (>95%) for all androgens measured across
sex/menopausal status groups. Spearman ranked correlations for 9 hormones
measured in the comparison laboratory were high (>0.85), suggesting good
agreement. CONCLUSION: Our high-performance LC-MS/MS assays of 11 androgens,
including adrenal and gonadal androgenic precursors and their 5alpha-reduced
metabolites demonstrated excellent laboratory reproducibility, and good
comparability with an established method that measured 9 of the 11 hormones
tested. The serum androgen metabolite assays are suitable for use in
epidemiologic research.
PMID- 26416144
TI - Oral health and post-discharge complications in stroke survivors.
PMID- 26416143
TI - A systematic review of training programmes for recruiters to randomised
controlled trials.
AB - BACKGROUND: Recruitment to randomised controlled trials (RCTs) is often
difficult. Clinician related factors have been implicated as important reasons
for low rates of recruitment. Clinicians (doctors and other health professionals)
can experience discomfort with some underlying principles of RCTs and experience
difficulties in conveying them positively to potential trial participants.
Recruiter training has been suggested to address identified problems but a
synthesis of this research is lacking. The aim of our study was to systematically
review the available evidence on training interventions for recruiters to
randomised trials. METHODS: Studies that evaluated training programmes for trial
recruiters were included. Those that provided only general communication training
not linked to RCT recruitment were excluded. Data extraction and quality
assessment were completed by two reviewers independently, with a third author
where necessary. RESULTS: Seventeen studies of 9615 potentially eligible titles
and abstracts were included in the review: three randomised controlled studies,
two non-randomised controlled studies, nine uncontrolled pre-test/post-test
studies, two qualitative studies, and a post-training questionnaire survey. Most
studies were of moderate or weak quality. Training programmes were mostly set
within cancer trials, and usually consisted of workshops with a mix of health
professionals over one or two consecutive days covering generic and trial
specific issues. Recruiter training programmes were well received and some
increased recruiters' self-confidence in communicating key RCT concepts to
patients. There was, however, little evidence that this training increased actual
recruitment rates or patient understanding, satisfaction, or levels of informed
consent. CONCLUSIONS: There is a need to develop recruiter training programmes
that can lead to improved recruitment and informed consent in randomised trials.
PMID- 26416145
TI - Novel Therapies for Chronic Lymphocytic Leukemia: A Canadian Perspective.
AB - Chronic lymphocytic leukemia (CLL) is the most common adult lymphoproliferative
disorder in Western countries. The current standard of care for CLL is
chemoimmunotherapy, typically with fludarabine, cyclophosphamide, and rituximab
(FCR). However, most patients with CLL are elderly with comorbidities and are
unable to tolerate FCR. In order to choose the best treatment for each individual
patient, physicians must balance efficacy with toxicity. In addition, most
currently available treatments are ineffective in CLL patients with loss of TP53.
Two groups of novel therapeutic agents-anti-CD20 monoclonal antibodies and small
molecule inhibitors-are attempting to address these issues, and 5 of these agents
have progressed to phase 3 trials: obinutuzumab, idelalisib, ibrutinib,
venetoclax (ABT-199), and duvelisib (IPI-145). We present the current evidence
for these novel agents in the treatment of CLL, along with the perspectives of 4
Canadian oncology experts.
PMID- 26416146
TI - Towards an understanding of the structural basis for insect olfaction by odorant
receptors.
AB - Insects have co-opted a unique family of seven transmembrane proteins for odour
sensing. Odorant receptors are believed to have evolved from gustatory receptors
somewhere at the base of the Hexapoda and have expanded substantially to become
the dominant class of odour recognition elements within the Insecta. These
odorant receptors comprise an obligate co-receptor, Orco, and one of a family of
highly divergent odorant "tuning" receptors. The two subunits are thought to come
together at some as-yet unknown stoichiometry to form a functional complex that
is capable of both ionotropic and metabotropic signalling. While there are still
no 3D structures for these proteins, site-directed mutagenesis, resonance energy
transfer, and structural modelling efforts, all mainly on Drosophila odorant
receptors, are beginning to inform hypotheses of their structures and how such
complexes function in odour detection. Some of the loops, especially the second
extracellular loop that has been suggested to form a lid over the binding pocket,
and the extracellular regions of some transmembrane helices, especially the third
and to a less extent the sixth and seventh, have been implicated in ligand
recognition in tuning receptors. The possible interaction between Orco and tuning
receptor subunits through the final intracellular loop and the adjacent
transmembrane helices is thought to be important for transducing ligand binding
into receptor activation. Potential phosphorylation sites and a calmodulin
binding site in the second intracellular loop of Orco are also thought to be
involved in regulating channel gating. A number of new methods have recently been
developed to express and purify insect odorant receptor subunits in recombinant
expression systems. These approaches are enabling high throughput screening of
receptors for agonists and antagonists in cell-based formats, as well as
producing protein for the application of biophysical methods to resolve the 3D
structure of the subunits and their complexes.
PMID- 26416147
TI - Early BCG vaccine to low-birth-weight infants and the effects on growth in the
first year of life: a randomised controlled trial.
AB - BACKGROUND: Randomised trials have shown that early Bacille Calmette-Guerin (BCG)
vaccine reduces overall neonatal and infant mortality. However, no study has
examined how BCG affects growth. We investigated the effect on infant growth of
early BCG vaccine given to low-birth-weight (LBW) infants. METHODS: Two-thousand
three hundred forty-three LBW infants were randomly allocated 1:1 to "early BCG"
(intervention group) or "late BCG" (current practice). Furthermore, a subgroup (N
= 1717) were included in a two-by-two randomised trial in which they were
additionally randomised 1:1 to vitamin A supplementation (VAS) or placebo.
Anthropometric measurements were obtained 2, 6, and 12 months after enrolment.
RESULTS: Overall there was no effect of early BCG on growth in the first year of
life. The effect of early BCG on weight and mid-upper-arm circumference at 2
months tended to be beneficial among girls but not among boys (interaction
between "early BCG" and sex: weight p = 0.03 and MUAC p = 0.04). This beneficial
effect among girls was particularly seen among the largest infants weighing 2.0
kg or more at inclusion. CONCLUSION: Though BCG vaccination is not recommended to
be given to LBW infants at birth in Guinea-Bissau, early BCG had no negative
effect on infant growth and may have had a beneficial effect for girls. TRIAL
REGISTRATION NUMBER: ClinicalTrials.gov (NCT00146302).
PMID- 26416148
TI - Retinoic acid metabolism proteins are altered in trichoblastomas induced by mouse
papillomavirus 1.
AB - Skin cancer burden is significant as treatment costs have skyrocketed to $8.1
million annually and some forms metastasize, such as cutaneous squamous cell
carcinoma (cSCC) and melanoma. cSCC is caused by altered growth factor signaling
induced by chemical carcinogens, ultraviolet light (UV) exposure, and infections
with papillomaviruses (PVs). One of the few options for preventing cSCC in high
risk patients is oral retinoids. While much is understood about retinoid
treatments and metabolism in mouse models of chemically and UV exposure induced
cSCC, little is known about the role of retinoids in PV-induced cSCC. To better
understand how retinoid metabolism is altered in cSCC, we examined the expression
of this pathway in the newly discovered mouse papillomavirus (MmuPV1), which
produces trichoblastomas in dorsal skin but not cSCC. We found significant
increases in a rate-limiting enzyme involved in retinoic acid synthesis and
retinoic acid binding proteins, suggestive of increased RA synthesis, in MmuPV1
induced tumors in B6.Cg-Foxn1(nu)/J mice. Similar increases in these proteins
were seen after acute UVB exposure in Crl:SKH1-Hr(hr) mice and in regressing pre
cancerous lesions in a chemically-induced mouse model, suggesting a common
mechanism in limiting the progression of papillomas to full blown cSCC.
PMID- 26416149
TI - Bone growth resumption following in vivo static and dynamic compression removals
on rats.
AB - Mechanical loadings influence bone growth and are used in pediatric treatments of
musculoskeletal deformities. This in vivo study aimed at evaluating the effects
of static and dynamic compression application and subsequent removal on bone
growth, mineralization and neuropathic pain markers in growing rats. Forty-eight
immature rats (28 days old) were assigned in two groups (2- and 4 weeks
experiment duration) and four subgroups: control, sham, static, and dynamic.
Controls had no surgery. A micro-loading device was implanted on the 6th and 8th
caudal vertebrae of shams without loading, static loading at 0.2 MPa or dynamic
loading at 0.2 MPa +/- 30% and 0.1 Hz. In 2-week subgroups, compression was
maintained for 15 days prior to euthanasia, while in 4- week subgroups,
compression was removed for 10 additional days. Growth rates, histomorphometric
parameters and mineralization intensity were quantified and compared. At 2 weeks,
growth rates and growth plate heights of loaded groups (static/dynamic)were
significantly lower than shams (p b 0.01).However, at 4 weeks, both growth rates
and growth plate heights of loaded groups were similar to shams. At 4 weeks,
alizarin red intensity was significantly higher in dynamics compared to shams (p
b 0.05) and controls (p b 0.01). Both static and dynamic compressions enable
growth resumption after loading removal, while preserving growth plate
histomorphometric integrity. However, mineralization was enhanced after dynamic
loading removal only. Dynamic loading showed promising results for fusionless
treatment approaches for musculoskeletal deformities.
PMID- 26416151
TI - Immunotherapy: Anti-PD-1 therapies-a new first-line option in advanced melanoma.
PMID- 26416150
TI - Knee loading protects against osteonecrosis of the femoral head by enhancing
vessel remodeling and bone healing.
AB - Osteonecrosis of the femoral head is a serious orthopedic problem. Moderate loads
with knee loading promote bone formation, but their effects on osteonecrosis have
not been investigated. Using a rat model, we examined a hypothesis that knee
loading enhances vessel remodeling and bone healing through the modulation of the
fate of bone marrow-derived cells. In this study, osteonecrosis was induced by
transecting the ligamentum teres followed by a tight ligature around the femoral
neck. For knee loading, 5 N loads were laterally applied to the knee at 15 Hz for
5 min/day for 5 weeks. Changes in bone mineral density (BMD) and bone mineral
content (BMC) of the femur were measured by pDEXA, and ink infusion was performed
to evaluate vessel remodeling. Femoral heads were harvested for histomorphometry,
and bone marrow-derived cells were isolated to examine osteoclast development and
osteoblast differentiation. The results showed that osteonecrosis significantly
induced bone loss, and knee loading stimulated both vessel remodeling and bone
healing. The osteonecrosis group exhibited the lowest trabecular BV/TV (p b
0.001) in the femoral head, and lowest femoral BMD and BMC (both p b 0.01).
However, knee loading increased trabecular BV/TV (p b 0.05) as well as BMD (pb
0.05) and BMC (p b 0.01). Osteonecrosis decreased the vessel volume (pb 0.001),
vessel number (pb 0.001) and VEGF expression (p b 0.01), and knee loading
increased them (pb 0.001, pb 0.001 and p b 0.01). Osteonecrosis activated
osteoclast development, and knee loading reduced its formation, migration,
adhesion and the level of "pit" formation (pb 0.001, pb 0.01, pb 0.001 and pb
0.001). Furthermore, knee loading significantly increased osteoblast
differentiation and CFU-F (both p b 0.001). A significantly positive correlation
was observed between vessel remodeling and bone healing (both p b 0.01). These
results indicate that knee loading could be effective in repair osteonecrosis of
the femoral head in a rat model. This effect might be attributed to promoting
vessel remodeling, suppressing osteoclast development, and increasing osteoblast
and fibroblast differentiation. In summary, the current study suggests that knee
loading might potentially be employed as a non-invasive therapy for osteonecrosis
of the femoral head.
PMID- 26416152
TI - Surgical treatment of nonpalpable primary invasive and in situ breast cancer.
AB - Breast cancer is the most-common cancer among women worldwide, and over one-third
of all cases diagnosed annually are nonpalpable at diagnosis. The increasingly
widespread implementation of breast-screening programmes, combined with the use
of advanced imaging modalities, such as magnetic resonance imaging (MRI), will
further increase the numbers of patients diagnosed with this disease. The current
standard management for nonpalpable breast cancer is localized surgical excision
combined with axillary staging, using sentinel-lymph-node biopsy in the
clinically and radiologically normal axilla. Wire-guided localization (WGL)
during mammography is a method that was developed over 40 years ago to enable
lesion localization preoperatively; this technique became the standard of care in
the absence of a better alternative. Over the past 20 years, however, other
technologies have been developed as alternatives to WGL in order to overcome the
technical and outcome-related limitations of this technique. This Review
discusses the techniques available for the surgical management of nonpalpable
breast cancer; we describe their advantages and disadvantages, and highlight
future directions for the development of new technologies.
PMID- 26416153
TI - Haematological cancer: PROLONGing PFS with ofatumumab in patients with CLL.
PMID- 26416154
TI - Brimonidine gel 0.33% rapidly improves patient-reported outcomes by controlling
facial erythema of rosacea: a randomized, double-blind, vehicle-controlled study.
AB - BACKGROUND: Facial redness contributes to impaired psychosocial functioning in
rosacea patients and the only approved treatment for erythema is topical
brimonidine gel 0.33%. OBJECTIVES: To evaluate patient-reported outcomes, as well
as efficacy and safety, in subjects with self-perceived severe erythema treated
with brimonidine gel 0.33% compared to vehicle. METHODS: An 8-day multicenter,
randomized study comparing once-daily brimonidine gel 0.33% with vehicle gel
using a facial redness questionnaire, subject satisfaction questionnaire and a
patient diary of facial redness control to assess patient-reported outcomes.
RESULTS: Of the 92 included subjects with self-perceived severe erythema, very
few were satisfied with their appearance at baseline (4.2% brimonidine group, 0
vehicle group). On Day 8, significantly more brimonidine group subjects were
satisfied with their facial appearance compared to vehicle group (36.9% vs.
21.5%; P < 0.05), with the overall treatment effect (69.6% vs. 40.4%; P < 0.01),
and with the improvement in their facial redness (67.4% vs. 33.3%; P < 0.001).
More brimonidine group subjects were able to control their facial redness daily
(e.g. 83.0% vs. 38.9% on Day 1). On Day 8, significantly more brimonidine group
subjects than vehicle group had at least a one-grade improvement from baseline in
the Clinician Erythema Assessment score (71.7% vs. 35.7%; P = 0.0011) and Patient
Self-Assessment score (76.1% vs. 47.6%; P = 0.004). More subjects in the
brimonidine group (29.2%) reported treatment-related adverse events than in the
vehicle group (15.9%) but most were mild and transient. CONCLUSIONS: Once-daily
brimonidine gel 0.33% allowed patients to rapidly control their facial redness
and significantly improved patient-reported outcomes in the treatment of
persistent facial erythema of rosacea.
PMID- 26416155
TI - Hybrid Monoterpenoid Indole Alkaloids Obtained as Artifacts from Rauvolfia
tetraphylla.
AB - Five new hybrid monoterpenoid indole alkaloids bearing an unusual 2,2-dimethyl-4
oxopiperidin-6-yl moiety, namely rauvotetraphyllines F-H (1, 3, 4), 17-epi
rauvotetraphylline F (2) and 21-epi-rauvotetraphylline H (5), were isolated from
the aerial parts of Rauvolfia tetraphylla. Their structures were established by
extensive spectroscopic analysis. The new alkaloids were evaluated for their
cytotoxicity in vitro against five human cancer cell lines.
PMID- 26416156
TI - Adult social position and sick leave: the mediating effect of physical workload.
AB - OBJECTIVE: This study aimed to quantify how much of the adult social gradient in
sick leave can be attributed to the mediating role of physical workload while
accounting for the role of childhood and adolescent social position and
neuroticism. METHODS: Our sample consisted of 2099 women and 1229 men from a
Norwegian birth cohort study (born 1967-1976) who participated in the Nord
Trondelag Health Study (2006-2008) (HUNT3). Data on sick leave (defined as >16
calendar days; 2006-2009) and social position during childhood, adolescence, and
adulthood were obtained from national registers. Study outcome was time-to-first
sick leave spell. Physical workload and neuroticism were self-reported in HUNT3.
Mediating effects through physical workload were estimated using a method based
on the additive hazards survival model. RESULTS: A hypothetical change from
highest to lowest group in adult social position was, for women, associated with
51.6 [95% confidence interval (95% CI) 24.7-78.5] additional spells per 100,000
person-days at risk, in a model adjusted for childhood and adolescent social
position and neuroticism. The corresponding rate increase for men was 41.1 (95%
CI 21.4-60.8). Of these additional spells, the proportion mediated through
physical workload was 24% (95% CI 10-49) and 30% (95% CI 10-63) for women and
men, respectively. CONCLUSIONS: The effect of adult social position on sick leave
was partly mediated through physical workload, even while accounting for earlier
life course factors. Our findings provide support that interventions aimed at
reducing physical workload among those with lower adult social position could
reduce sick leave risk.
PMID- 26416157
TI - Drug hypersensitivity in children: report from the pediatric task force of the
EAACI Drug Allergy Interest Group.
AB - When questioned, about 10% of the parents report suspected hypersensitivity to at
least one drug in their children. However, only a few of these reactions can be
confirmed as allergic after a diagnostic workup. There is still a lack of
knowledge on drug hypersensitivity (DH) epidemiology, clinical spectrum, and
appropriate diagnostic methods particularly in children. Meanwhile, the tools
used for DH management in adults are applied also for children. Whereas this
appears generally acceptable, some aspects of DH and management differ with age.
Most reactions in children are still attributed to betalactams. Some
manifestations, such as nonsteroidal anti-inflammatory drug-associated angioedema
and serum sickness-like reactions, are more frequent among young patients as
compared to adults. Risk factors such as viral infections are particularly
frequent in children, making the diagnosis challenging. The practicability and
validity of skin test and other diagnostic procedures need further assessment in
children. This study presents an up-to-date review on epidemiology, clinical
spectrum, diagnostic tools, and current management of DH in children. A new
general algorithm for the study of these reactions in children is proposed. Data
are presented focusing on reported differences between pediatric and adult
patients, also identifying unmet needs to be addressed in further research.
PMID- 26416159
TI - Smoking history is associated to cognitive impairment in Parkinson's disease.
AB - INTRODUCTION: Patients with Parkinson's disease (PD) are more likely to suffer
from cognitive impairment and dementia than healthy older adults. The aim of this
study was to investigate smoking history as a risk factor for cognitive decline
in PD. METHOD: One hundred thirty-nine PD patients aged 50 years and older (Hoehn
and Yahr = 1-3) were recruited from a clinical database. Global cognitive
function was assessed with the Mini-Mental State Examination (MMSE) and smoking
history was investigated as part of a standard clinical interview. A multiple
linear regression analysis was used to develop a model for predicting
participants' MMSE scores from age, education, Hoehn and Yahr stage, disease
duration, the number of vascular risk factors and the number of smoking pack
years. RESULTS: The regression model significantly accounted for 22.9% of the
variance in MMSE scores. Significant predictors were education (beta = .312, p <
.001), age (beta = -.215, p = .013) and total smoking pack-years (beta = -.180, p
= .029). In former smokers, the number of years since quitting had no effect on
global cognition and there were no significant difference between patients who
had quit smoking more than 10 years ago and those who had quit less than 10 years
ago, F(1, 63) = 1.72, p = .195. CONCLUSION: Smoking history was associated to
global cognitive impairment in PD even in patients who had quit smoking. These
results are in line with findings in healthy older adults that have linked
smoking to cognitive impairment, global brain atrophy and functional changes.
Future studies should consider a broader assessment of cognitive functions.
PMID- 26416158
TI - Mitochondrial ADP/ATP exchange inhibition: a novel off-target mechanism
underlying ibipinabant-induced myotoxicity.
AB - Cannabinoid receptor 1 (CB1R) antagonists appear to be promising drugs for the
treatment of obesity, however, serious side effects have hampered their clinical
application. Rimonabant, the first in class CB1R antagonist, was withdrawn from
the market because of psychiatric side effects. This has led to the search for
more peripherally restricted CB1R antagonists, one of which is ibipinabant.
However, this 3,4-diarylpyrazoline derivative showed muscle toxicity in a pre
clinical dog study with mitochondrial dysfunction. Here, we studied the molecular
mechanism by which ibipinabant induces mitochondrial toxicity. We observed a
strong cytotoxic potency of ibipinabant in C2C12 myoblasts. Functional
characterization of mitochondria revealed increased cellular reactive oxygen
species generation and a decreased ATP production capacity, without effects on
the catalytic activities of mitochondrial enzyme complexes I-V or the complex
specific-driven oxygen consumption. Using in silico off-target prediction
modelling, combined with in vitro validation in isolated mitochondria and
mitoplasts, we identified adenine nucleotide translocase (ANT)-dependent
mitochondrial ADP/ATP exchange as a novel molecular mechanism underlying
ibipinabant-induced toxicity. Minor structural modification of ibipinabant could
abolish ANT inhibition leading to a decreased cytotoxic potency, as observed with
the ibipinabant derivative CB23. Our results will be instrumental in the
development of new types of safer CB1R antagonists.
PMID- 26416162
TI - Layer-dependent surface potential of phosphorene and anisotropic/layer-dependent
charge transfer in phosphorene-gold hybrid systems.
AB - The surface potential and the efficiency of interfacial charge transfer are
extremely important for designing future semiconductor devices based on the
emerging two-dimensional (2D) phosphorene. Here, we directly measured the strong
layer-dependent surface potential of mono- and few-layered phosphorene on gold,
which is consistent with the reported theoretical prediction. At the same time,
we used an optical way photoluminescence (PL) spectroscopy to probe charge
transfer in the phosphorene-gold hybrid system. We firstly observed highly
anisotropic and layer-dependent PL quenching in the phosphorene-gold hybrid
system, which is attributed to the highly anisotropic/layer-dependent interfacial
charge transfer.
PMID- 26416161
TI - Neural responses to kindness and malevolence differ in illness and recovery in
women with anorexia nervosa.
AB - In anorexia nervosa, problems with social relationships contribute to illness,
and improvements in social support are associated with recovery. Using the
multiround trust game and 3T MRI, we compare neural responses in a social
relationship in three groups of women: women with anorexia nervosa, women in long
term weight recovery from anorexia nervosa, and healthy comparison women.
Surrogate markers related to social signals in the game were computed each round
to assess whether the relationship was improving (benevolence) or deteriorating
(malevolence) for each subject. Compared with healthy women, neural responses to
benevolence were diminished in the precuneus and right angular gyrus in both
currently-ill and weight-recovered subjects with anorexia, but neural responses
to malevolence differed in the left fusiform only in currently-ill subjects.
Next, using a whole-brain regression, we identified an office assessment, the
positive personalizing bias, that was inversely correlated with neural activity
in the occipital lobe, the precuneus and posterior cingulate, the bilateral
temporoparietal junctions, and dorsal anterior cingulate, during benevolence for
all groups of subjects. The positive personalizing bias is a self-report measure
that assesses the degree with which a person attributes positive experiences to
other people. These data suggest that problems in perceiving kindness may be a
consistent trait related to the development of anorexia nervosa, whereas
recognizing malevolence may be related to recovery. Future work on social brain
function, in both healthy and psychiatric populations, should consider positive
personalizing biases as a possible marker of neural differences related to
kindness perception.
PMID- 26416160
TI - Histopathological features of endometrial carcinomas associated with POLE
mutations: implications for decisions about adjuvant therapy.
AB - AIMS: To characterize the histomorphological features of endometrial carcinomas
(ECs) harbouring polymerase epsilon (POLE) mutations. METHODS AND RESULTS: Forty
three ECs with POLE mutations were compared with a cohort of 202 ECs. Most POLE
mutated ECs were endometrioid [34/43 (79%)]; the remaining tumours were mixed
[6/43 (14%)], serous [2/43 (5%)], and clear cell [1/43 (2%)]. The endometrioid
carcinomas were predominantly International Federation of Gynecology and
Obstetrics grade 3 (27/43, 63%). The histotype distribution did not differ from
that of control ECs (P = 0.69), but the grade of the EC was higher (P < 0.0005).
Both nuclear grade and mitotic index were significantly higher in POLE-mutated
ECs than in the comparison cohort. POLE-mutated ECs were associated with
peritumoral lymphocytes and numerous tumour-infiltrating lymphocytes.
Lymphovascular invasion was present in 20 of 43 tumours. Adjuvant radiotherapy
and adjuvant chemotherapy would be offered in up to 80% and 40% of patients,
respectively, on the basis of stage, grade, lymphovascular invasion, and
histotype. CONCLUSIONS: POLE-mutated ECs are typically of high grade, with
prominent lymphocytic infiltration, but they are not sufficiently distinctive to
allow accurate diagnosis based on routine haematoxylin and eosin staining. Even
though POLE-mutated tumours are associated with an excellent prognosis, current
guidelines for giving adjuvant treatment for EC result in most patients receiving
adjuvant therapy.
PMID- 26416163
TI - Pain and Health-Related Quality of Life After Pediatric Inpatient Surgery.
AB - Around 4 million children undergo inpatient surgery in the United States each
year, however little is known about the impact of surgery and postoperative pain
on children's health-related quality of life (HRQOL) during the weeks and months
after surgery. We measured pain and HRQOL in a large, heterogeneous pediatric
postsurgical population from baseline to 1-month follow-up. Over a 20-month
period, parents of 915 children age 2 to 18 years (mean = 9.6 years), 50% male,
56% white, admitted to surgical services at a children's hospital enrolled in the
study. Parent participants reported on sociodemographics, child HRQOL, and pain
characteristics at baseline and 1 month after discharge. Although most of the
children recovered to baseline by 1 month after hospital discharge, 23% of
children had a significant decline in HRQOL. Logistic regression analyses found
that increasing child age (odds ratio = 2.1 for age 13-18 years) and the presence
of moderate-severe postsurgical pain at 1 month (odds ratio = 5.7) were
significantly associated with deterioration in HRQOL from baseline to 1-month
follow-up (P < .05 for each variable). Although HRQOL returns to the baseline
level for most children, a sizeable proportion have significant deterioration in
HRQOL associated with continued postsurgical pain at 1 month after hospital
discharge from surgery. PERSPECTIVE: This study addresses an important gap in the
literature, examining pain and health-related quality of life in a broad
population of children undergoing a wide range of inpatient surgeries. Evaluation
of inpatient health services from a patient and family perspective is essential
in evaluating outcomes of surgical care.
PMID- 26416164
TI - Strategies to engage stakeholders in research to improve acute care delivery.
AB - Many families involved in research are well versed in the care system due to
chronic conditions. Engagement of families of children with serious acute
illnesses is infrequent, and no studies have documented the feasibility or
acceptability of different methods of family engagement. We describe a model used
in the Hospital-to-Home Outcomes study, which utilized a novel approach of short
term focused engagement of families and other stakeholders to incorporate the
unique viewpoints of families whose care experience is primarily focused around
the period surrounding their child's hospitalization for acute illness.
PMID- 26416165
TI - Response to imatinib in patient with corticosteroid-unresponsive idiopathic
hypereosinophilic syndrome.
PMID- 26416166
TI - Identity management and sense of belonging to gay community among young rural
Thai same-sex attracted men: implications for HIV prevention and treatment.
AB - Young Thai men who have sex with men continue to have high HIV prevalence and
incidence in spite of much investment in community-based prevention approaches.
To make HIV services more appropriate for same-sex attracted young men in
Thailand, it needs to be considered how target groups view themselves and manage
their identities. This paper derives from a qualitative study of 25 same-sex
attracted rural young Thai men. It identifies five tactics men employed to manage
the discrepancy between their preferences and parental/societal expectations
regarding gender and sexuality, and discusses how the young men viewed themselves
in the wider context of Thai society, including whether they felt part of a
separate gay community. Participants usually did not adopt a gay social identity
and were reluctant to join in gay community activities beyond dating. Hence, they
would likely experience barriers in accessing gay community-based HIV services.
HIV services targeting young same-sex attracted Thai men need to be diversified
if they are to be more inclusive, appropriate and effective.
PMID- 26416168
TI - A tiered asthma hazard characterization and exposure assessment approach for
evaluation of consumer product ingredients.
AB - Asthma is a complex syndrome with significant consequences for those affected.
The number of individuals affected is growing, although the reasons for the
increase are uncertain. Ensuring the effective management of potential exposures
follows from substantial evidence that exposure to some chemicals can increase
the likelihood of asthma responses. We have developed a safety assessment
approach tailored to the screening of asthma risks from residential consumer
product ingredients as a proactive risk management tool. Several key features of
the proposed approach advance the assessment resources often used for asthma
issues. First, a quantitative health benchmark for asthma or related endpoints
(irritation and sensitization) is provided that extends qualitative hazard
classification methods. Second, a parallel structure is employed to include dose
response methods for asthma endpoints and methods for scenario specific exposure
estimation. The two parallel tracks are integrated in a risk characterization
step. Third, a tiered assessment structure is provided to accommodate different
amounts of data for both the dose-response assessment (i.e., use of existing
benchmarks, hazard banding, or the threshold of toxicological concern) and
exposure estimation (i.e., use of empirical data, model estimates, or exposure
categories). Tools building from traditional methods and resources have been
adapted to address specific issues pertinent to asthma toxicology (e.g., mode-of
action and dose-response features) and the nature of residential consumer product
use scenarios (e.g., product use patterns and exposure durations). A case study
for acetic acid as used in various sentinel products and residential cleaning
scenarios was developed to test the safety assessment methodology. In particular,
the results were used to refine and verify relationships among tiered approaches
such that each lower data tier in the approach provides a similar or greater
margin of safety for a given scenario.
PMID- 26416167
TI - Antibiotics in neonatal life increase murine susceptibility to experimental
psoriasis.
AB - Psoriasis is an inflammatory skin disease affecting ~2% of the world's
population, but the aetiology remains incompletely understood. Recently,
microbiota have been shown to differentially regulate the development of
autoimmune diseases, but their influence on psoriasis is incompletely understood.
We show here that adult mice treated with antibiotics that target Gram-negative
and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by
imiquimod, with decreased pro-inflammatory IL-17- and IL-22-producing T cells.
Surprisingly, mice treated neonatally with these antibiotics develop exacerbated
psoriasis induced by imiquimod or recombinant IL-23 injection when challenged as
adults, with increased IL-22-producing gammadelta(+) T cells. 16S rRNA gene
compositional analysis reveals that neonatal antibiotic-treatment dysregulates
gut and skin microbiota in adults, which is associated with increased
susceptibility to experimental psoriasis. This link between neonatal antibiotic
mediated imbalance in microbiota and development of experimental psoriasis
provides precedence for further investigation of its specific aetiology as it
relates to human psoriasis.
PMID- 26416170
TI - Multivalency effects on Pseudomonas aeruginosa biofilm inhibition and dispersal
by glycopeptide dendrimers targeting lectin LecA.
AB - The galactose specific lectin LecA partly mediates the formation of antibiotic
resistant biofilms by Pseudomonas aeruginosa, an opportunistic pathogen causing
lethal airways infections in immunocompromised and cystic fibrosis patients,
suggesting that preventing LecA binding to natural saccharides might provide new
opportunities for treatment. Here 8-fold (G3) and 16-fold (G4) galactosylated
analogs of GalAG2, a tetravalent G2 glycopeptide dendrimer LecA ligand and P.
aeruginosa biofilm inhibitor, were obtained by convergent chloroacetyl thioether
(ClAc) ligation between 4-fold or 8-fold chloroacetylated dendrimer cores and
digalactosylated dendritic arms. Hemagglutination inhibition, isothermal
titration calorimetry and biofilm inhibition assays showed that G3 dendrimers
bind LecA slightly better than their parent G2 dendrimers and induce complete
biofilm inhibition and dispersal of P. aeruginosa biofilms, while G4 dendrimers
show reduced binding and no biofilm inhibition. A binding model accounting for
the observed saturation of glycopeptide dendrimer galactosyl groups and LecA
binding sites is proposed based on the crystal structure of a G3 dendrimer LecA
complex.
PMID- 26416169
TI - Response of plant nutrient stoichiometry to fertilization varied with plant
tissues in a tropical forest.
AB - Plant N:P ratios are widely used as indices of nutrient limitation in terrestrial
ecosystems, but the response of these metrics in different plant tissues to
altered N and P availability and their interactions remains largely unclear. We
evaluated changes in N and P concentrations, N:P ratios of new leaves (<1 yr),
older leaves (>1 yr), stems and mixed fine roots of seven species after 3-years
of an N and P addition experiment in a tropical forest. Nitrogen addition only
increased fine root N concentrations. P addition increased P concentrations among
all tissues. The N * P interaction reduced leaf and stem P concentrations,
suggesting a negative effect of N addition on P concentrations under P addition.
The reliability of using nutrient ratios as indices of soil nutrient availability
varied with tissues: the stoichiometric metrics of stems and older leaves were
more responsive indicators of changed soil nutrient availability than those of
new leaves and fine roots. However, leaf N:P ratios can be a useful indicator of
inter-specific variation in plant response to nutrients availability. This study
suggests that older leaf is a better choice than other tissues in the assessment
of soil nutrient status and predicting plant response to altered nutrients using
nutrients ratios.
PMID- 26416171
TI - Do age and sex impact on the absolute cell numbers of human brain regions?
AB - What is the influence of sex and age on the quantitative cell composition of the
human brain? By using the isotropic fractionator to estimate absolute cell
numbers in selected brain regions, we looked for sex- and age-related differences
in 32 medial temporal lobes (comprised basically by the hippocampal formation,
amygdala and parahippocampal gyrus), sixteen male (29-92 years) and sixteen
female (25-82); and 31 cerebella, seventeen male (29-92 years) and fourteen
female (25-82). These regions were dissected from the brain, fixed and
homogenized, and then labeled with a DNA-marker (to count all nuclei) and with a
neuron-specific nuclear marker (to estimate neuron number). Total number of cells
in the medial temporal lobe was found to be 1.91 billion in men, and 1.47 billion
in women, a difference of 23 %. This region showed 34 % more neurons in men than
in women: 525.1 million against 347.4 million. In contrast, no sex differences
were found in the cerebellum. Regarding the influence of age, a quadratic
correlation was found between neuronal numbers and age in the female medial
temporal lobe, suggesting an early increase followed by slight decline after age
50. The cerebellum showed numerical stability along aging for both neurons and
non-neuronal cells. In sum, results indicate a sex-related regional difference in
total and neuronal cell numbers in the medial temporal lobe, but not in the
cerebellum. On the other hand, aging was found to impact on cell numbers in the
medial temporal lobe, while the cerebellum proved resilient to neuronal losses in
the course of life.
PMID- 26416173
TI - The sentinel node procedure in early stage cervical cancer, taking the next step;
a diagnostic review.
AB - OBJECTIVE: Recent reviews on the sentinel lymph node (SLN) procedure in cervical
cancer have shown that bilateral SLN detection and ultra staging are safe and
superior options compared to a unilateral detection, frozen section and H&E
analysis. So far, nobody identified a subgroup of patients in whom a SLN
procedure may replace pelvic lymph node dissection (PLND). METHODS: We searched
PubMed, Embase, CINAHL and Cochrane from inception up to November 26, 2014.
Studies reporting SLN detection, and/or histological outcome of the SLN were
included. Methodological quality was assessed with the Quality Assessment of
Diagnostic Accuracy Studies tool by two independent reviewers. Data to complete
2*2 contingency tables were obtained, and patient-, study- and technique
characteristics were extracted. Results were pooled and plotted in forest plots.
RESULTS: Forty-seven studies (4130 patients) were analyzed. Pooled data of
diagnostic accuracy on ultra staging (18 studies; 1275 patients) showed a
sensitivity of 94% (95% CI 80-99%) and negative predictive values ranging between
91 and 100%. After ultra staging, 19 false negative results remained.
Prerequisites such as early FIGO stage (IA2, IB1, IIA primary tumor size <40mm),
no suspicious pre-, and per-operative lymph nodes, and bilateral negative SLNs
after ultra staging resulted in 1 remaining false negative result among 1257
patients (0.08%). Pooled data on a combined tracer in early stage cervical cancer
patients with primary tumor size <20mm (6 studies; 276 patients) resulted in 87%
bilateral SLN detection. CONCLUSIONS: Early stage cervical cancer patients (FIGO
IA2, IB1, IIA primary tumor size <40mm) who have no suspicious pre-, and per
operative lymph nodes, and have bilateral negative SLNs after ultra staging, have
a residual risk of 0.08% (1/1257) on occult metastases. On the basis of these
results we recommend not to perform a full PLND in these patients.
PMID- 26416174
TI - Outcome of elderly patients who receive intensive care at a regional hospital in
Hong Kong.
AB - OBJECTIVE: To evaluate the clinical outcome (180-day mortality) of very elderly
critically ill patients (age >=80 years) and compare with those aged 60 to 79
years. DESIGN: Historical cohort study. SETTING: Regional hospital, Hong Kong.
PATIENTS: Patients aged >=60 years admitted between 1 January 2009 and 31
December 2013 to the Intensive Care Unit of the hospital. RESULTS: Over 5 years,
4226 patients aged >=60 years were admitted (55.5% total intensive care unit
admissions), of whom 32.8% were aged >=80 years. The proportion of patients aged
>=80 years increased over 5 years. As expected, those aged >=80 years carried
more significant co-morbidities and a higher disease severity compared with those
aged 60 to 79 years. They required more mechanical ventilatory support, were less
likely to receive renal replacement therapy, and had a higher intensive care
unit/hospital/180-day mortality compared with those aged 60 to 79 years.
Nonetheless, 71.8% were discharged home and 62.2% survived >180 days following
intensive care unit admission. Cox regression analysis revealed that Acute
Physiology and Chronic Health Evaluation IV-minus-Age score, emergency admission,
intensive care unit admission due to cardiovascular problem, neurosurgical cases,
presence of significant co-morbidities (diabetes mellitus, metastatic carcinoma,
leukaemia, or myeloma), and requirement for mechanical ventilation independently
predicted 180-day mortality. CONCLUSIONS: The proportion of critically ill
patients aged >=80 years increased over a 5-year period. Despite having more
significant co-morbidities, greater disease severity, and higher intensive care
unit/hospital/180-day mortality rate compared with those aged 60 to 79 years,
71.8% of those >=80 years could be discharged home and 62.2% survived >180 days
following intensive care unit admission. Disease severity, presence of co
morbidities, requirement for mechanical ventilation, emergency cases, and
admission diagnosis independently predicted 180-day mortality.
PMID- 26416172
TI - A roadmap for precision medicine in the epilepsies.
AB - Technological advances have paved the way for accelerated genomic discovery and
are bringing precision medicine clearly into view. Epilepsy research in
particular is well suited to serve as a model for the development and deployment
of targeted therapeutics in precision medicine because of the rapidly expanding
genetic knowledge base in epilepsy, the availability of good in-vitro and in-vivo
model systems to efficiently study the biological consequences of genetic
mutations, the ability to turn these models into effective drug-screening
platforms, and the establishment of collaborative research groups. Moving
forward, it is crucial that these collaborations are strengthened, particularly
through integrated research platforms, to provide robust analyses both for
accurate personal genome analysis and gene and drug discovery. Similarly, the
implementation of clinical trial networks will allow the expansion of patient
sample populations with genetically defined epilepsy so that drug discovery can
be translated into clinical practice.
PMID- 26416175
TI - Why do Hong Kong patients need total hip arthroplasty? An analysis of 512 hips
from 1998 to 2010.
AB - INTRODUCTION: The number of patients undergoing total hip replacement surgeries
has increased as a result of a rise in the ageing population. This study reviewed
the demographics and disease spectrum leading to primary total hip replacement in
the Chinese population from 1998 to 2010. METHODS: This case series was conducted
in a university teaching hospital in Hong Kong. Data from the prospective joint
registry of all patients who underwent primary total hip replacement from January
1998 to December 2010 were reviewed. Patients' age and sex, diagnosis, as well as
the Harris Hip Scores before operation and at the last follow-up were described.
RESULTS: There were 512 primary total hip replacements performed on 419 patients
(43.4% males) during the study period. All had clinical follow-up for at least 2
years. The mean age of the patients was 57.6 (standard deviation, 16.6) years. In
males, the main aetiology was osteonecrosis (50.9%), ankylosing spondylitis
(19.5%), and post-traumatic arthritis (8.5%). For females, it was osteonecrosis
(33.0%), primary osteoarthritis (18.8%), and post-traumatic arthritis (15.8%).
Alcohol-induced (52.5%) and idiopathic (40.7%) was the most common cause of
osteonecrosis in males and females, respectively. The mean preoperative Harris
Hip Score and that at last follow-up was 43.9 (standard deviation, 18.3) and 89.7
(standard deviation, 13.0), respectively. CONCLUSIONS: Osteonecrosis was the most
common aetiology leading to total hip replacement although there were different
causes in both sexes leading to it. The clinical result in terms of Harris Hip
Score was good for all patients who required total hip replacement.
PMID- 26416176
TI - Dual use of VA and non-VA hospitals by Veterans with multiple hospitalizations.
AB - BACKGROUND: Veterans who are hospitalized in both VA and non-VA hospitals within
a short timespan may be at risk for fragmented or conflicting care. To determine
the characteristics of these "dual users," we analyzed administrative hospital
discharge data for VA-enrolled veterans of any age in seven states, including any
VA or non-VA hospitalizations they had in 2004-2007. METHOD: For VA enrollees in
Arizona, Iowa, Louisiana, Florida, South Carolina, Pennsylvania, or New York in
2007, we merged 2004-2007 discharge data for all VA hospitalizations and all non
VA hospitalizations listed in state health department or hospital association
databases. For patients hospitalized in 2007, we compared those younger or older
than 65 years who had one or multiple hospitalizations during the year, split
into users of VA hospitals, non-VA hospitals, or both ("dual users"), on
demographics, priority for VA care, travel times, principal diagnoses, co
morbidities, lengths of stay, and prior (2004-2006) hospitalizations, using chi
square analysis or ANOVA. Multiply hospitalized patients were compared with
multinomial logistic regressions to predict non-VA and dual use. Payers for non
VA hospitalizations also were compared across groups. RESULTS: Of unique
inpatients in 2007, 38 % of those 65 or older were hospitalized more than once
during the year, as were 32 % of younger patients; 3 and 8 %, respectively, were
dual users. Dual users averaged the most index-year (3.7) and prior (1.5)
hospitalizations, split evenly between VA and non-VA. They also had higher rates
of admission for circulatory diseases, symptoms/signs/ill-defined conditions, and
injury and poisoning, and more admissions for multiple diagnostic categories;
among younger patients they had the highest rate of mental disorders admissions.
Higher income, non-rural residence, greater time to VA care, lower VA priority,
prior non-VA hospitalization, no prior VA hospitalization, and several medical
categories predicted greater non-VA use. Among younger patients, however, mental
disorders predicted more dual use but less exclusively non-VA use. Dual users'
non-VA admissions were more likely than others' to be covered by payers other
than Medicare or commercial insurance. CONCLUSIONS: Younger dual users require
more medical and psychiatric treatment, and rely more on government funding
sources. Effective care coordination for these inpatients might improve outcomes
while reducing taxpayer burden.
PMID- 26416177
TI - Feasibility and effectiveness of the baby friendly community initiative in rural
Kenya: study protocol for a randomized controlled trial.
AB - BACKGROUND: Interventions promoting optimal infant and young child nutrition
could prevent a fifth of under-5 deaths in countries with high mortality. Poor
infant and young child feeding practices are widely documented in Kenya, with
potential detrimental effects on child growth, health and survival. Effective
strategies to improve these practices are needed. This study aims to pilot
implementation of the Baby Friendly Community Initiative (BFCI), a global
initiative aimed at promoting optimal infant and young child feeding practices,
to determine its feasibility and effectiveness with regards to infant feeding
practices, nutrition and health outcomes in a rural setting in Kenya. METHODS:
The study, employing a cluster-randomized trial design, will be conducted in
rural Kenya. A total of 12 clusters, constituting community units within the
government's Community Health Strategy, will be randomized, with half allocated
to the intervention and the other half to the control arm. A total of 812
pregnant women and their respective children will be recruited into the study.
The mother-child pairs will be followed up until the child is 6 months old.
Recruitment will last approximately 1 year from January 2015, and the study will
run for 3 years, from 2014 to 2016. The intervention will involve regular
counseling and support of mothers by trained community health workers and health
professionals on maternal, infant and young child nutrition. Regular assessment
of knowledge, attitudes and practices on maternal, infant and young child
nutrition will be done, coupled with assessment of nutritional status of the
mother-child pairs and morbidity for the children. Statistical methods will
include analysis of covariance, multinomial logistic regression and multilevel
modeling. The study is funded by the NIH and USAID through the Program for
Enhanced Research (PEER) Health. DISCUSSION: Findings from the study outlined in
this protocol will inform potential feasibility and effectiveness of a community
based intervention aimed at promoting optimal breastfeeding and other infant
feeding practices. The intervention, if proved feasible and effective, will
inform policy and practice in Kenya and similar settings, particularly regarding
implementation of the baby friendly community initiative. TRIAL REGISTRATION:
ISRCTN03467700 ; Date of Registration: 24 September 2014.
PMID- 26416178
TI - A rare accessory muscle in the hand--the flexor digitorum superficialis indicis.
AB - Accessory muscles are easily overlooked during imaging evaluation. Although
usually discovered incidentally, they are occasionally symptomatic. With
increasing utilization of cross-sectional imaging, the radiologist should be
prepared to readily identify these anomalous muscles. It is particularly
important to distinguish these anatomical variants from soft-tissue tumors prior
to invasive intervention, reserving biopsy and surgery for children who are
symptomatic. This report discusses a case of a flexor digitorum superficialis
indicis muscle, an extremely rare but well-described accessory muscle, presenting
as a painful mass in a 15-year-old girl. The report includes the clinical
presentation, radiologic findings, and the significance to management.
PMID- 26416179
TI - Hypodermin A, a potential agent for prevention of allogeneic acute rejection.
AB - Immunosuppressive agents play an important role in the success of organ
transplantation, however the chronic toxicity of these agents is a major issue
over the long-term. Hypodermin A (HA) is an enzyme secreted by the larvae of
Hypoderma lineatum (Diptera: Oestridae), and has been implicated in
immunosuppression in cattle. Malassagne et al. have demonstrated that HA can
degrade the C3 protein, and could be used to prevent hyperacute xenogeneic
rejection. We found that overexpression of HA in RAW264.7 cells induced
significant secretion of prostaglandin E2 (PGE2), which mediates a variety of
innate and adaptive immune responses through four E-type prostanoid (EP) receptor
subtypes (EP1-4). PGE2 is useful in the management of allogeneic acute rejection.
In addition, we found that induction of PGE2 expression downregulates the
expression of interferon (IFN)-gamma and interleukin (IL)-2, and promotes the
secretion of IL-10 in vitro through the EP4 receptor. It was previously shown
that activation of IL-2 and IFN-gamma is involved in allograft acute rejection.
IL-10 is known to prevent inflammation, and can improve allograft survival rates.
We concluded that besides preventing hyperacute xenogeneic rejection, HA might
also be a potential therapeutic candidate for ameliorating acute rejection during
allotransplantation.
PMID- 26416180
TI - Microvascular integrity plays an important role for graft survival after
experimental skin transplantation.
AB - BACKGROUND: Every transplanted organ relies on a reliable and sound vascular
system. Therefore, our study focused on the investigation if platelet inhibition
alone or combined with mTOR-inhibition has a beneficial effect on the
microvascular integrity in allogeneic murine skin grafts. METHODS: Skin
transplantation was performed from fully MHC-mismatched C57BL/6 (H-2b) donors to
CBA/J (H-2k) recipient mice. Skin allograft recipients were assigned to several
experimental groups and either treated with clopidogrel alone, everolimus alone
or a combination of both. Graft survival was evaluated and transplants were
harvested after 8 days and analyzed for CD31 and C4d by immunohistochemistry.
RESULTS: Untreated allografts showed a reduced amount of CD31 on postoperative
day 8 as well as an increase in C4d compared to isografts. All treated animals
showed a significant improvement regarding CD31 [1577.7 +/- 200.4
(clopidogrel)/1702.8 +/- 151.1 (clopidogrel + everolimus) vs. 479.7 +/- 184.2
(control), n = 8, p b 0.05] and C4d [420.9 +/- 70.9 (clopidogrel)/324.5 +/- 77.3
(clopidogrel + everolimus) vs. 772.4 +/- 159.7 (control), n = 8, p b 0.05]. In
addition, skin grafts of animals treated with clopidogrel and everolimus survived
significantly longer compared to untreated controls [19.2 +/- 4.2 d vs. 12.8 +/-
2.4 d, n= 10, p b 0.05]. CONCLUSION: In this study we could show that clopidogrel
alone and in combination with everolimus substantially improved microvascular
integrity and resulted in increased survival time of skin grafts.
PMID- 26416181
TI - Relationship between developmental canal stenosis and surgical results of
anterior decompression and fusion in patients with cervical spondylotic
myelopathy.
AB - BACKGROUND: Anterior cervical decompression and fusion (ACDF) has long been the
preferred treatment for cervical spondylotic myelopathy (CSM). However, few
studies have focused on surgical results of CSM in patients with developmental
canal stenosis (DCS). The purpose of this study was to investigate DCS as a
comorbidity in patients with CSM and the correlation between surgical results and
DCS. METHODS: From January 1995 to December 2005, 122 patients treated with ACDF
for CSM were enrolled in this retrospective study. Pavlov's ratio was used to
evaluate cervical spinal canal size, with a value of < 0.82 at least one level
indicating DCS. Patients were divided into two groups: those with DCS
preoperatively (DCS group, n = 50 [41.0 %]) and those without DCS (non-DCS group,
n = 72). Clinical data and radiological parameters were compared between groups.
RESULTS: There were no significant differences in preoperative and 2-year follow
up Japanese Orthopedic Association scores between groups. Both groups achieved
satisfactory fusion rates (DCS, 92.0 %; non-DCS, 93.0 %). Adjacent-segment
degeneration (ASD) was detected in 66.0 % of patients in the DCS group and in
43.0 % of patients in the non-DCS group (p = 0.01). However, there was no
significant difference in the incidence of ASD requiring surgery between groups
(p = 0.20). DISCUSSION: DCS is a common comorbidity in patients with CSM. The
findings of this study have added knowledge on the correlation between DCS and
ASD after anterior fusion surgery. CONCLUSIONS: DCS did not affect neurologic
improvement postoperatively at short-term follow-up. Although DCS increased the
incidence of ASD after anterior fusion, it did not predict ASD requiring surgery.
Therefore, patients with DCS must receive close follow-up.
PMID- 26416182
TI - Nonsense mutations in the rhodopsin gene that give rise to mild phenotypes
trigger mRNA degradation in human cells by nonsense-mediated decay.
AB - Eight different nonsense mutations in the human rhodopsin gene cause retinitis
pigmentosa (RP), an inherited degenerative disease of the retina that can lead to
complete blindness. Although all these nonsense mutations lead to premature
termination codons (PTCs) in rhodopsin mRNA, some display dominant inheritance,
while others are recessive. Because nonsense-mediated decay (NMD) can degrade
mRNAs containing PTCs and modulate the inheritance patterns of genetic diseases,
we asked whether any of the nonsense mutations in the rhodopsin gene generated
mRNAs that were susceptible to degradation by NMD. We hypothesized that nonsense
mutations that caused mild RP phenotypes would trigger NMD, whereas those that
did not engage NMD would cause more severe RP phenotypes-presumably due to the
toxicity of the truncated protein. To test our hypothesis, we transfected human
rhodopsin nonsense mutants into HEK293 and HT1080 human cells and measured
transcript levels by qRT-PCR. In both cell lines, rhodopsin mutations Q64X and
Q344X, which cause severe phenotypes that are dominantly inherited, yielded the
same levels of rhodopsin mRNA as wild type. By contrast, rhodopsin mutations
W161X and E249X, which cause recessive RP, showed decreased rhodopsin mRNA
levels, consistent with NMD. Rhodopsin mutant Y136X, a dominant mutation that
causes late-onset RP with a very mild pathology, also gave lower mRNA levels.
Treatment of cells with Wortmannin, an inhibitor of NMD, eliminated the
degradation of Y136X, W161X, and E249X rhodopsin mRNAs. These results suggest
that NMD modulates the severity of RP in patients with nonsense mutations in the
rhodopsin gene.
PMID- 26416183
TI - Association of Autophagy in the Cell Death Mediated by Dihydrotestosterone in
Autoreactive T Cells Independent of Antigenic Stimulation.
AB - Gender disparity is well documented in the mouse model of experimental autoimmune
encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139-151, in which
female, but not male, SJL mice show a chronic relapsing-remitting paralysis.
Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity
of EAE, but the underlying mechanisms of its protective effects are unclear.
Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151,
we tested the hypothesis that DHT selectively modulates the expansion and
functionalities of antigen-specific T cells. Unexpectedly, we noted that DHT
induced cell death in antigen-specific, autoreactive T cells, but the effects
were not selective, because both proliferating and non-proliferating cells were
equally affected independent of antigenic stimulation. Furthermore, DHT-exposed
PLP 139-151-specific T cells did not show any shift in cytokine production;
rather, frequencies of cytokine-producing PLP-specific T cells were significantly
reduced, irrespective of T helper (Th) 1, Th2, and Th17 subsets of cytokines. By
evaluating cell death and autophagy pathways, we provide evidence for the
induction of autophagy to be associated with cell death caused by DHT. Taken
together, the data provide new insights into the role of DHT and indicate that
cell death and autophagy contribute to the therapeutic effects of androgens in
autoreactive T cells.
PMID- 26416184
TI - The Quality of Genetic Counseling and Connected Factors as Evaluated by Male
BRCA1/2 Mutation Carriers in Finland.
AB - There is little written about the quality of genetic counseling for men with the
BRCA1/2 mutation. The purpose of this study was to describe the quality of
genetic counseling and connected factors according to Finnish male BRCA1/2
mutation carriers' (n = 35) perspectives and reasons for seeking genetic
counseling. Data were collected from the Departments of Clinical Genetics at five
Finnish university hospitals. The exploratory study design was conducted using a
51-item questionnaire based on a previously devised quality of counseling model
and analyzed using non-parametric tests and principle content analysis. The
satisfaction level with genetic counseling was high, especially with regard to
the content of genetic counseling. The benefit of genetic counseling on the
quality of life differed significantly (p < 0.001-0.009) from other factors. In
particular, genetic counseling was in some cases associated to reduce the quality
of life. Only 49 % of the male carriers felt they received sufficient counseling
on social support. Attention to individual psychosocial support was proposed as
an improvement to genetic counseling. Primary and secondary reasons for seeking
genetic counseling and background information, such as education, affected the
perceived quality of genetic counseling. The results of the study could be used
to tailor genetic counseling for male BRCA1/2 mutation carriers.
PMID- 26416185
TI - Assessment of the Readability of Genetic Counseling Patient Letters.
AB - Patient letters are a powerful tool that genetic counselors use to communicate
with their patients. Patient letters are often sent to provide information on a
new diagnosis, reiterate test results, and to serve as a permanent record of the
visit. Patient letters, however, are only helpful if the patients can understand
them. More than 50 % of the US population reads below a 9th grade reading level
and over one-third of the population has low health literacy skills. In this
study we evaluate the readability of genetic counseling patient letters by
assessing reading level, image use, and terminology use. One hundred forty-nine
genetic counselors participated in the survey and of these, 79 submitted a sample
patient letter. Analyses of the letters revealed a mean reading level of 10.93.
On average, 6 genetic terms were included in each letter, and only 25 % of these
terms were defined. Analyses of survey responses revealed over 75 % of the
genetic counselors did not include images in their patient letters. These results
indicate there is room for improvement in order to make genetic counseling
patient letters more accessible to the general population.
PMID- 26416186
TI - Direct Observation of Long Electron-Hole Diffusion Distance in CH3NH3PbI3
Perovskite Thin Film.
AB - In high performance perovskite based solar cells, CH3NH3PbI3 is the key material.
We carried out a study on charge diffusion in spin-coated CH3NH3PbI3 perovskite
thin film by transient fluorescent spectroscopy. A thickness-dependent
fluorescent lifetime was found. By coating the film with an electron or hole
transfer layer, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) or 2,2',7,7'
tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (Spiro-OMeTAD)
respectively, we observed the charge transfer directly through the fluorescence
quenching. One-dimensional diffusion model was applied to obtain long charge
diffusion distances in thick films, which is ~1.7 MUm for electrons and up to
~6.3 MUm for holes. Short diffusion distance of few hundreds of nanometer
[corrected] was also observed in thin films. This thickness dependent charge
diffusion explained the formerly reported short charge diffusion distance (~100
nm) in films and resolved its confliction to thick working layer (300-500 nm) in
real devices. This study presents direct support to the high performance
perovskite solar cells and will benefit the devices' design.
PMID- 26416187
TI - Temporal Trends in the Incidence and Natural History of Diverticulitis: A
Population-Based Study.
AB - OBJECTIVES: Data on the incidence and natural history of diverticulitis are
largely hospital-based and exclude the majority of diverticulitis patients, who
are treated in an outpatient setting for uncomplicated diverticulitis. We
assessed temporal trends in the epidemiology of diverticulitis in the general
population. METHODS: Through the Rochester Epidemiology Project we reviewed the
records of all individuals with a diagnosis of diverticulitis from 1980 to 2007
in Olmsted County, Minnesota, USA. RESULTS: In 1980-1989, the incidence of
diverticulitis was 115/100,000 person-years, which increased to 188/100,000 in
2000-2007 (P<0.001). Incidence increased with age (P<0.001); however, the
temporal increase was greater in younger people (P<0.001). Ten years after the
index and second diverticulitis episodes, 22% and 55% had a recurrence,
respectively. This recurrence rate was greater in younger people (hazard ratio
(HR) per decade 0.63; 95% confidence interval (CI), 0.59-0.66) and women (HR
0.68; 95% CI, 0.58-0.80). Complications were seen in 12%; this rate did not
change over time. Recurrent diverticulitis was associated with a decreased risk
of complications (P<0.001). Age was associated with increased risk of local (odds
ratio (OR) 1.27 per decade; 95% CI, 1.04-1.57) and systemic (OR 1.83; 95% CI,
1.20-2.80) complications. Survival after diverticulitis was lower in older people
(P<0.001) and men (P<0.001) and worsened over time (P<0.001). The incidence of
surgery for diverticulitis did not change from 1980 to 2007. CONCLUSIONS: The
incidence of diverticulitis has increased by 50% in 2000-2007 compared with 1990
1999, and more so in younger people. Complications are relatively uncommon.
Recurrent diverticulitis is frequent but typically uncomplicated. Younger people
with diverticulitis have less severe disease, more recurrence, and better
survival.
PMID- 26416188
TI - Autofluorescence-Directed Confocal Endomicroscopy in Combination With a Three
Biomarker Panel Can Inform Management Decisions in Barrett's Esophagus.
AB - OBJECTIVES: Barrett's esophagus (BE) surveillance with white-light endoscopy and
quadrantic biopsies (Seattle protocol) is resource intensive and limited by
sampling error. Previous work suggests that autofluorescence imaging (AFI) in
combination with a molecular panel might reduce the number of biopsies, but this
was not sufficiently sensitive for low-grade dysplasia, now a point for
endoscopic intervention. Here we used AFI to direct narrow-field imaging tools
for real-time optical assessment of dysplasia and biopsies for a biomarker panel.
We compared the new diagnostic algorithm with the current standard. METHODS: A
total of 55 patients with BE were recruited at a single tertiary referral center.
Patients underwent high-resolution endoscopy followed by AFI. AFI-targeted areas
(n=194) were examined in turn by narrow-band imaging with magnification (NBIz)
and probe-based confocal laser endomicroscopy (pCLE). Biopsies were taken from
AFI-targeted areas and tested using an established molecular panel comprising
aneuploidy plus cyclin A and p53 immunohistochemistry. RESULTS: In the per
patient analysis the overall sensitivity and specificity of AFI-targeted pCLE
were 100% and 53.6% for high-grade dysplasia/intramucosal cancer and 96.4% and
74.1% for any grade of dysplasia, respectively. NBIz had equal specificity for
dysplasia detection (74.1%), but significantly lower sensitivity (57.1%) than
pCLE. The time required to perform AFI-targeted pCLE was shorter that that taken
by the Seattle protocol (P=0.0004). We found enrichment of molecular
abnormalities in areas with optical dysplasia by pCLE (P<0.001), regardless of
histologic dysplasia. The addition of the 3-biomarker panel reduced the false
positive rate of pCLE by 50%, leading to sensitivity and specificity for any
grade of dysplasia of 89.2% and 88.9%, respectively. CONCLUSIONS: The combination
of pCLE on AFI-targeted areas and a 3-biomarker panel identifies patients with
dysplasia.
PMID- 26416189
TI - The Link between the Appendix and Ulcerative Colitis: Clinical Relevance and
Potential Immunological Mechanisms.
AB - The human appendix has long been considered as a vestigial organ, an organ that
has lost its function during evolution. In recent years, however, reports have
emerged that link the appendix to numerous immunological functions in humans.
Evidence has been presented for an important role of the appendix in maintaining
intestinal health. This theory suggests that the appendix may be a reservoir or
'safe house' from which the commensal gut flora can rapidly be reestablished if
it is eradicated from the colon. However, the appendix may also have a role in
the development of inflammatory bowel disease (IBD). Several large
epidemiological cohort studies have demonstrated the preventive effect of
appendectomy on the development of ulcerative colitis, a finding that has been
confirmed in murine colitis models. In addition, current studies are examining
the possible therapeutic effect of an appendectomy to modulate disease course in
patients with ulcerative colitis. This literature review assesses the current
knowledge about the clinical and immunological aspects of the vermiform appendix
in IBD and suggests that the idea of the appendix as a vestigial remnant should
be discarded.
PMID- 26416190
TI - Low-grade dysplasia in ulcerative colitis: risk factors for developing high-grade
dysplasia or colorectal cancer.
AB - OBJECTIVES: The aim of this study was to identify risk factors associated with
development of high-grade dysplasia (HGD) or colorectal cancer (CRC) in
ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD).
METHODS: Patients with histologically confirmed extensive UC, who were diagnosed
with LGD between 1993 and 2012 at St Mark's Hospital, were identified and
followed up to 1 July 2013. Demographic, endoscopic, and histological data were
collected and correlated with the development of HGD or CRC. RESULTS: A total of
172 patients were followed for a median of 48 months from the date of initial LGD
diagnosis (interquartile range (IQR), 15-87 months). Overall, 33 patients
developed HGD or CRC (19.1% of study population; 20 CRCs) during study period.
Multivariate Cox proportional hazard analysis revealed that macroscopically non
polypoid (hazard ratio (HR), 8.6; 95% confidence interval (CI), 3.0-24.8;
P<0.001) or invisible (HR, 4.1; 95% CI, 1.3-13.4; P=0.02) dysplasia, dysplastic
lesions >=1 cm in size (HR, 3.8; 95% CI, 1.5-13.4; P=0.01), and a previous
history of "indefinite for dysplasia" (HR, 2.8; 95% CI, 1.2-6.5; P=0.01) were
significant contributory factors for HGD or CRC development. Multifocal dysplasia
(HR, 3.9; 95% CI, 1.9-7.8; P<0.001), metachronous dysplasia (HR, 3.5; 95% CI, 1.6
7.5; P=0.001), or a colonic stricture (HR, 7.4; 95% CI, 2.5-22.1; P<0.001) showed
only univariate correlation to development of HGD or CRC. CONCLUSIONS: Lesions
that are non-polypoid or endoscopically invisible, large (>=1 cm), or preceded by
indefinite dysplasia are independent risk factors for developing HGD or CRC in UC
patients diagnosed with LGD.
PMID- 26416191
TI - Clinical and pathophysiological consequences of alterations in the microbiome in
cirrhosis.
AB - Cirrhosis is a major cause of mortality worldwide. Exponential rises in
prevalence have been observed secondary to increases in obesity and alcohol
consumption. Multiple lines of evidence implicate gut-derived bacteria and
bacterial ligands as a central driver of pathogenesis. Recent developments in
culture-independent techniques have facilitated a more accurate description of
microbiome composition in cirrhosis and led to the description of measures of
dysbiosis shown to be associated with disease. More importantly, metagenomic
studies are adding to an understanding of the functional contribution of the
microbiota and may prove to be a more clinically relevant biomarker than
phylogenetic studies. Much like other dysbiotic states such as inflammatory bowel
disease, the microbiota in cirrhosis is characterized by a low microbial and
genetic diversity. Therapeutic strategies to diminish this process are currently
limited to selective intestinal decontamination with antibiotics. This review
summarizes the available data and develops a framework for the use of current and
future treatment strategies to diminish the consequences of dysbiosis in
cirrhosis. Interventional strategies to bind bacterial products in the gut lumen
and blood, and modulate the magnitude of host sensing mechanisms remain an unmet
clinical need. A greater understanding of the host-microbiota interaction in
cirrhosis is of key importance to inform future interventional strategies to
diminish the currently escalating burden of the disease.
PMID- 26416192
TI - Risk of Celiac Disease in the First- and Second-Degree Relatives of Patients With
Celiac Disease: A Systematic Review and Meta-Analysis.
AB - OBJECTIVES: First-degree relatives (FDRs) of patients with celiac disease (CD)
are at high risk for CD and prevalence among them varies from 1.6 to 38%. The
risk of having CD among FDRs if the FDR is sister, brother, mother, father, son,
or daughter of index patient with CD is not known. We conducted a meta-analysis
and calculated pooled prevalence of CD among FDRs, second-degree relatives
(SDRs), and specific relations with index patient. METHODS: On search of
literature, 2,259 articles appeared of which 54 articles were included in this
meta-analysis. Diagnosis of CD was based on standard criteria. RESULTS: Pooled
prevalence of CD was 7.5% (95% confidence interval (CI) 6.3%, 8.8%) in 10,252
FDRs and 2.3% (95% CI 1.3%, 3.8%) in 642 SDRs. Pooled prevalence of CD was
highest in siblings (8.9%), followed by offsprings (7.9%) and parents (3.0%).
Female FDRs had higher prevalence than male FDRs (8.4% vs. 5.2%, P=0.047). While
sisters and daughters of index patient had the highest risk of having CD (1 in 7
and 1 in 8, respectively), the risk was 1 in 13 in sons, 1 in 16 in brothers, 1
in 32 in mothers, and 1 in 33 in fathers. There were also differences in the
pooled prevalence of CD in FDRs according to their geographic location.
CONCLUSIONS: Pooled prevalence of CD among FDRs is 7.5% and varies considerably
with their relationship with the index patient. The risk of CD in FDRs also
varies according to gender and geographical location.
PMID- 26416193
TI - Long-Term Loss of Response in Proton Pump Inhibitor-Responsive Esophageal
Eosinophilia Is Uncommon and Influenced by CYP2C19 Genotype and
Rhinoconjunctivitis.
AB - OBJECTIVES: Proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is
diagnosed in at least one-third of patients with suspected eosinophilic
esophagitis (EoE). We aimed to evaluate the durability and factors influencing
long-term efficacy of PPI therapy. METHODS: Retrospective multicenter cohort
study of patients with PPI-REE who had at least 12 months of follow-up. PPI
therapy was tapered to the lowest dose, which maintained clinical remission.
Primary outcomes were the proportion of patients with loss of histological
response (<15 eos/HPF) and predictors of loss of response. CYP2C19 polymorphisms
were determined from blood samples in a subset of patients. RESULTS: Seventy-five
PPI-REE patients were included (mean follow-up 26 months (12-85)), of whom fifty
five (73%) had sustained histological remission on low-dose PPI therapy. Loss of
response was significantly higher in those patients with a CYP2C19 rapid
metabolizer genotype (36% vs. 6%, P = 0.01) and with rhinoconjunctivitis (40% vs.
13%, P = 0.007). On the multivariate analysis, a CYP2C19 rapid metabolizer
genotype (odds ratio (OR) 12.5; 95% confidence interval (CI): 1.3-115.9) and
rhinoconjunctivitis (OR 8.6; 95% CI: 1.5-48.7) were independent predictors of
loss of response. Among relapsing patients, eosinophilia was limited to the
distal esophagus in 14/20 (70%). Nine of ten relapsers, with distal eosinophilia,
all showing a CYP2C19 rapid metabolizer genotype, regained histological remission
after PPI dose intensification. CONCLUSIONS: Most PPI-REE patients remain in long
term remission on low-dose PPI therapy. CYP2C19 rapid metabolizer genotypes and
rhinoconjunctivitis were independent predictors of loss of response to PPI, but
patients frequently responded to PPI dose escalation.
PMID- 26416194
TI - Changing Nomenclature for PBC: From 'Cirrhosis' to 'Cholangitis'.
PMID- 26416195
TI - Right Or Left in COLonoscopy (ROLCOL)? A Randomized Controlled Trial of Right-
versus Left-Sided Starting Position in Colonoscopy.
AB - OBJECTIVES: Colonoscopy is technically challenging and can cause discomfort for
patients. We aimed to test whether right-sided starting position for colonoscopy
would result in shorter procedure time and greater patient comfort when compared
with conventional left-sided starting position. METHODS: We conducted a
randomized controlled trial in which patients were randomized to begin in either
the right- (RL) or conventional left-lateral (LL) position. One hundred and sixty
three adult patients undergoing scheduled colonoscopy were stratified by age,
gender, body mass index, and experience of the endoscopist. Patients were then
randomized 1:1 in permuted blocks. The primary outcome measure was time to cecal
intubation and secondary outcome measures included patient comfort that was
evaluated by visual analog comfort scale. RESULTS: Median time to reach the cecum
was quicker when colonoscopy began with patients positioned RL rather than LL
(P=0.0078). Moreover, patients found RL more comfortable than LL (P=0.02).
Multiple linear regression confirmed starting position in colonoscopy as an
independent determinant of time to reach the cecum (P=0.007). Women and those who
had previously undergone abdominal surgery gained the greatest benefit from right
sided positioning (RL vs. LL: 498 vs. 824 s; P=0.03 and 498 vs. 797 s; P=0.006,
respectively). CONCLUSIONS: Our study reveals that right-sided positioning at the
start of colonoscopy results in more comfortable and quicker procedures. Of the
factors identified by multiple linear regression to independently have an impact
on time to reach the cecum, only starting position is modifiable. Right-sided
starting position may therefore be of benefit in colonoscopy, in particular for
women and patients who have previously undergone abdominal surgery.
PMID- 26416197
TI - A review of sarcocystosis in camels and redescription of Sarcocystis cameli and
Sarcocystis ippeni sarcocysts from the one-humped camel (Camelus dromedarius).
AB - There is considerable confusion concerning Sarcocystis species in camels. Five
species: Sarcocystis cameli, Sarcocystis ippeni, Sarcocystis camelicanis,
Sarcocystis camelocanis and Sarcocystis miescheri were named with inadequate
descriptions and no type specimens. Here, we review literature on sarcocystosis
in camels worldwide and redescribe structure of S. cameli and S. ippeni
sarcocysts by light- and transmission electron microscopy (LM and TEM). Eight
sarcocysts from the oesophagi of two camels (Camelus dromedarius) from Egypt were
studied. By LM, all sarcocysts were thin-walled with barely visible projections
on the cyst walls. By TEM, two structurally distinct sarcocysts were recognized
by unique villar protrusions (vp) not found in sarcocysts from any other host.
Sarcocysts of S. cameli had vp of type 9 j. The sarcocyst wall had upright
slender vp, up to 3.0 uM long and 0.5 uM wide; the total thickness of the
sarcocyst wall with ground substance (gs) layer was 3.5 uM. On each vp, there
were rows of knob-like protrusions that appeared to be interconnected. The vp had
microtubules that originated at midpoint of the gs and continued up to the tip;
microtubules were smooth, without any granules or dense areas. Bradyzoites were
approximately 14-15 * 3-4 uM in size with typical organelles. Sarcocystis ippeni
sarcocysts had type 32 sarcocyst wall characterized by conical vp with an
electron dense knob. The total thickness of the sarcocyst wall (from the base of
gs to vp tip) was 2.3-3.0 uM. The vp were up to 1.2 uM wide at the base and 0.25
uM at the tip. Microtubules in vp originated at midpoint of gs and continued up
to tip; microtubules were criss-crossed, smooth and without granules or dense
areas. Bradyzoites were 12.0-13.5 * 2.0-3.0 uM in size. Sarcocystis camelicanis,
S. camelocanis and S. miescheri are considered invalid.
PMID- 26416198
TI - B-1 cells contribute to susceptibility in experimental infection with Leishmania
(Leishmania) chagasi.
AB - The immune response to leishmaniasis is complex, and the result of infection
depends on both the genetic composition of the Leishmania species and the
immunity of the host. Clinical and experimental evidence suggest that the
activation of B cells leads to exacerbation of visceral leishmaniasis. However,
the role of B-1 cells (a subtype of B lymphocytes) in the pathogenesis of
experimental visceral leishmaniasis has not yet been elucidated. In this study,
we investigated the importance of B-1 cells in experimental infection with
Leishmania. (L.) chagasi. Our results showed that BALB/XID mice (X-linked
immunodeficient mice which are genetically deficient in B-1 cells) infected with
L. (L.) chagasi for 45 days had a significant reduction in parasite load in the
spleen when compared with control mice. Cytokine analysis showed that the
BALB/XID mice had lower amounts of IL-10 in their sera compared with control
group. In addition, the transfer of B-1 cells from wild type mice into IL-10KO
animals led to an increase in susceptibility to L. (L.) chagasi infection in the
IL-10KO mice, suggesting that the IL-10 produced by these cells is important in
experimental infection. Our results suggest that B-1 cells may play an important
role in susceptibility to L. (L.) chagasi.
PMID- 26416199
TI - Regadenoson Stress Real-Time Myocardial Perfusion Echocardiography for Detection
of Coronary Artery Disease: Feasibility and Accuracy of Two Different Ultrasound
Contrast Agents.
AB - BACKGROUND: The aim of this study was to compare the efficacy of myocardial
perfusion (MP) and wall motion (WM) analysis obtained with real-time myocardial
contrast echocardiography (RTMCE) and two widely used contrast agents in
detecting coronary artery disease after injection of the vasodilator regadenoson.
METHODS: One hundred fifty patients were studied at two academic centers using
regadenoson (400-MUg intravenous bolus) vasodilator stress RTMCE (7.5% Optison
infusion [n = 50] or 1.5% Definity infusion [n = 100]). Both MP and WM with RTMCE
were analyzed at rest and after regadenoson bolus. Comparisons of WM and MP
sensitivity, specificity, and accuracy were made. Quantitative angiography was
performed in all patients within 1 month of the regadenoson stress study (>50%
and >70% diameter stenosis was considered significant). Reviewers were blinded to
all clinical and quantitative angiographic data. RESULTS: Rate-pressure product
after regadenoson was higher in Optison than Definity patients (P = .004). Using
a 50% diameter stenosis on quantitative angiography as a reference standard,
overall sensitivity, specificity, and accuracy for combined WM and MP analysis
were not different for both agents (Optison, 77%, 64%, and 73%; Definity, 80%,
74%, and 78%; P = NS). The sensitivity, specificity, and accuracy of WM analysis
alone for Optison were 68%, 71%, and 69% compared with 60%, 72%, and 66% for
Definity (P = NS). Adding MP analysis improved the sensitivity and accuracy of
Definity for detecting both >50% and >70% stenoses (P < .001 vs WM), while MP
analysis did not improve the sensitivity of Optison for detecting either >50 or
>70% stenoses. CONCLUSIONS: RTMCE during regadenoson stress using either Optison
or Definity is a rapid and effective method for the detection of coronary artery
disease. The ability of MP imaging to improve WM accuracy may depend on the rate
pressure product achieved.
PMID- 26416201
TI - An Ethnographic Meta-Synthesis of Three Southwestern Rural Studies.
AB - OBJECTIVE: The objectives were to synthesize cumulative findings across three
critical ethnographic, community-partnered studies in the southwestern United
States and to describe the process of meta-ethnography for that analysis. DESIGN
AND SAMPLE: The meta-ethnography followed the design of Noblit and Hare for
constructing an analysis of composite data, informed by community-based
participatory research and Stringer's ethnographic strategies of Look-Think-Act.
The three studies occurred in rural settings of Colorado and New Mexico, engaging
129 total participants, along with community organizations and agencies as
partners. METHODS: Methods consisted of detailed review of each original study,
mapping of major concepts and themes, and general analysis, interpretation, and
synthesis across the studies. RESULTS: Overall themes were: health is the
capacity to care for oneself and do work, meaningful relationships are key in
health care interactions, patterns of discrimination persist in rural settings,
poor literacy and health literacy are barriers, and food insecurity is a growing
concern for older rural adults. CONCLUSIONS: Resolutions involve practice,
policy, and research and must incorporate all stakeholder groups in rural
settings; a participatory approach is critical to prioritize and impact existing
inequities; and work is needed to extend education and understanding of multiple
cultures, groups, customs, and rural contexts.
PMID- 26416200
TI - Prospectively identified deficits in sagittal plane hip-ankle coordination in
female athletes who sustain a second anterior cruciate ligament injury after
anterior cruciate ligament reconstruction and return to sport.
AB - BACKGROUND: Athletes who return to sport after anterior cruciate ligament
reconstruction are at increased risk of future ACL injury. Altered coordination
of lower extremity motion may increase this risk. The purpose of this study was
to prospectively determine if altered lower extremity coordination patterns exist
in athletes who go on to sustain a 2nd anterior cruciate ligament injury.
METHODS: Sixty-one female athletes who were cleared to return to sport after
anterior cruciate ligament reconstruction were included. Hip-ankle coordination
was assessed prior to return to sport with a dynamic postural coordination task.
Within 12 months, 14 patients sustained a 2nd ACL injury. Fourteen matched
subjects were selected for comparative analysis. Cross-recurrence quantification
analysis characterized hip-ankle coordination patterns. A group * target speed
(slow vs. fast) * leg (involved vs. uninvolved) analysis of variance was used to
identify differences. FINDINGS: A main effect of group (P = 0.02) indicated that
the single injury group exhibited more stable hip-ankle coordination [166.2
(18.9)] compared to the 2nd injury group [108.4 (10.1)]. A leg * group
interaction was also observed (P = .04). The affected leg of the single injury
group exhibited more stable coordination [M = 187.1 (23.3)] compared to the
affected leg of the 2nd injury group [M = 110.13 (9.8)], P = 0.03.
INTERPRETATION: Hip-ankle coordination was altered in female athletes who
sustained a 2nd anterior cruciate ligament injury after return to sport. Failure
to coordinate lower extremity movement in the absence of normal knee
proprioception may place the knee at risk.
PMID- 26416202
TI - Hepatitis C-like viruses are produced in cells from rabbit and hare DNA.
AB - Hepatitis C virus (HCV), a major causative agent of acute and chronic liver
disease, belongs to the Flaviviridae family and contains a single-strand positive
sense RNA genome, which upon virus entry and uncoating, functions as mRNAs and
thus can be directly translated into proteins by host cell machinery. To date the
HCV origin remains unclear and HCV life cycle and pathogenesis are not
enlightened processes due to the absence of HCV efficient cell cultures systems
or animals models. Here we show that rabbit and hare HCV-like viruses, RHCV and
HHCV respectively, are formed after the inoculation of genomic DNA in Madin-Darby
bovine kidney cell line cultures. RHCV is closely related to the HCV-1a/HCV-1b
genotypes and HHCV is more closely related to the HCV-1b genotype. These findings
could contribute to the understanding of HCV origin as well as clarify the virus
life cycle, pathogenesis, evolution and diversity.
PMID- 26416203
TI - Dissecting susceptibility from exogenous triggers: the model of alopecia areata
and associated inflammatory skin diseases.
AB - BACKGROUND: Alopecia areata (AA) is a T-cell-driven autoimmune disease of the
hair follicle and frequently reported to be associated with inflammatory skin
diseases (ISD) such as atopic eczema (AE) or psoriasis. Interestingly, AA on the
one hand and both AE and psoriasis on the other hand are believed to be driven by
mutually antagonistic T-cell subsets. OBJECTIVE: To characterize AA-specific T
cell profiles and inflammatory pattern by intra-individual comparison of AA and
coexistent ISD. METHODS: 112 patients with AA were recruited and investigated for
coexisting ISD. In-depth analyses were performed in patients with AA and AE (n =
2), AA and psoriasis (n = 1), AA and psoriasis and AE (n = 1) and AA and lichen
planus (n = 1), using histology, immunohistochemistry and cytokine staining of T
cells isolated from lesional skin. RESULTS: Of 112 AA patients investigated, 23
suffered from an ISD. The prevalence of AE, vitiligo, psoriasis and lichen planus
was higher in the investigated AA cohort than in the normal population. The
clinical as well as histological phenotype of AA the coexistent ISD were
unequivocal. In line with this, T-cell infiltrates were found to be disease
characteristics with AA and lichen planus dominated by CD8+ and IFN-gamma+ TNF
alpha+ producing T cells while psoriasis lesions in the same patients were
dominated by IL-17+ and AE by IL-4+ T cells. CONCLUSION: AA patients have a
higher incidence of various T-cell-driven inflammatory skin diseases than the
normal population, a phenomenon which might relate to over-activation of skin
homing T cells and to specific immune triggers as the primary cause of
inflammation. More importantly, we showed that by using AA as a model disease,
our approach of intra-individual comparison of distinct inflammatory responses in
the same patient is feasible and offers the unique possibility to gain insights
into disease pathogenesis independent from genetic susceptibilities.
PMID- 26416204
TI - Antagonistic within-host interactions between plant viruses: molecular basis and
impact on viral and host fitness.
AB - Double infections of related or unrelated viruses frequently occur in single
plants, the viral agents being inoculated into the host plant simultaneously (co
infection) or sequentially (super-infection). Plants attacked by viruses activate
sophisticated defence pathways which operate at different levels, often at
significant fitness costs, resulting in yield reduction in crop plants. The
occurrence and severity of the negative effects depend on the type of within-host
interaction between the infecting viruses. Unrelated viruses generally interact
with each other in a synergistic manner, whereas interactions between related
viruses are mostly antagonistic. These can incur substantial fitness costs to one
or both of the competitors. A relatively well-known antagonistic interaction is
cross-protection, also referred to as super-infection exclusion. This type of
interaction occurs when a previous infection with one virus prevents or
interferes with subsequent infection by a homologous second virus. The current
knowledge on why and how one virus variant excludes or restricts another is
scant. Super-infection exclusion between viruses has predominantly been
attributed to the induction of RNA silencing, which is a major antiviral defence
mechanism in plants. There are, however, presumptions that various mechanisms are
involved in this phenomenon. This review outlines the current state of knowledge
concerning the molecular mechanisms behind antagonistic interactions between
plant viruses. Harmful or beneficial effects of these interactions on viral and
host plant fitness are also characterized. Moreover, the review briefly outlines
the past and present attempts to utilize antagonistic interactions among viruses
to protect crop plants against destructive diseases.
PMID- 26416205
TI - Pistachio (Pistacia vera L.) Detection and Quantification Using a Murine
Monoclonal Antibody-Based Direct Sandwich Enzyme-Linked Immunosorbent Assay.
AB - A commercially available direct sandwich enzyme-linked immunosorbent assay
(ELISA) (BioFront Technologies, Tallahassee, FL, USA) using murine anti-pistachio
monoclonal antibodies (mAbs) as capture and detection antibodies was evaluated.
The assay was sensitive (limit of detection = 0.09 +/- 0.02 ppm full fat
pistachio, linear detection range = 0.5-36 ppm, 50% maximum signal concentration
= 7.9 +/- 0.7 ppm), reproducible (intra- and inter-assay variability < 24% CV),
and rapid (post-extraction testing time ~ 1.5 h). The target antigen was stable
and detectable in whole pistachio seeds subjected to autoclaving (121 degrees C,
15 psi, 15, 30 min), blanching (100 degrees C, 5, 10 min), frying (191 degrees
C, 1 min), microwaving (500, 1000 W, 3 min), and dry roasting (140 degrees C, 30
min; 168 degrees C, 12 min). No cross-reactivity was observed in 156 food
matrices, each tested at 100,000 ppm, suggesting the ELISA to be pistachio
specific. The pistachio recovery ranges for spiked (10 ppm) and incurred (10
50000 ppm) food matrices were 93.1-125.6% and 35.7-112.2%, respectively. The
assay did not register any false-positive or -negative results among the tested
commercial and laboratory prepared samples.
PMID- 26416206
TI - Identifying the domains of context important to implementation science: a study
protocol.
AB - BACKGROUND: There is growing recognition that "context" can and does modify the
effects of implementation interventions aimed at increasing healthcare
professionals' use of research evidence in clinical practice. However, conceptual
clarity about what exactly comprises "context" is lacking. The purpose of this
research program is to develop, refine, and validate a framework that identifies
the key domains of context (and their features) that can facilitate or hinder (1)
healthcare professionals' use of evidence in clinical practice and (2) the
effectiveness of implementation interventions. METHODS/DESIGN: A multi-phased
investigation of context using mixed methods will be conducted. The first phase
is a concept analysis of context using the Walker and Avant method to distinguish
between the defining and irrelevant attributes of context. This phase will result
in a preliminary framework for context that identifies its important domains and
their features according to the published literature. The second phase is a
secondary analysis of qualitative data from 13 studies of interviews with 312
healthcare professionals on the perceived barriers and enablers to their
application of research evidence in clinical practice. These data will be
analyzed inductively using constant comparative analysis. For the third phase, we
will conduct semi-structured interviews with key health system stakeholders and
change agents to elicit their knowledge and beliefs about the contextual features
that influence the effectiveness of implementation interventions and healthcare
professionals' use of evidence in clinical practice. Results from all three
phases will be synthesized using a triangulation protocol to refine the context
framework drawn from the concept analysis. The framework will then be assessed
for content validity using an iterative Delphi approach with international
experts (researchers and health system stakeholders/change agents). DISCUSSION:
This research program will result in a framework that identifies the domains of
context and their features that can facilitate or hinder: (1) healthcare
professionals' use of evidence in clinical practice and (2) the effectiveness of
implementation interventions. The framework will increase the conceptual clarity
of the term "context" for advancing implementation science, improving healthcare
professionals' use of evidence in clinical practice, and providing greater
understanding of what interventions are likely to be effective in which contexts.
PMID- 26416207
TI - TriGlycerides and high-density lipoprotein cholesterol ratio compared with
homeostasis model assessment insulin resistance indexes in screening for
metabolic syndrome in the chinese obese children: a cross section study.
AB - BACKGROUND: Metabolic Syndrome (MS) is prevalant in China, especially according
to the pediatric obesity group. Based on the MS-CHN2012 definition for Chinese
children and adolescents the need to explore and establish a convienent MS
screening become imminent. This study aims to investigate the optimal cut-off
values, compare the accuracy for the (TriGlycerides (TG) to High-Density
Lipoprotein Cholesterol (HDL-C)) (TG/HDL-C) ratio and Homeostasis Model
Assessment Insulin Resistance (HOMA-IR) indexs to identify Metabolic Syndrome in
obese pediatric population in China. METHOD: A total sample of 976 children
(female 286 male 690, BMI > = 95 percentile) aged from 6-16 years underwent a
medical assessment including a physical examination and investigations of total
cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides,
insulin, glucose, and oral glucose tolerance test to identify the components of
Metabolic Syndrome. The validity and accuracy between TG/HDL-C ratio and HOMA-IR
were compared by Receiver Operating Characteristics analysis (ROC). RESULT:
TG/HDL-C ratio achieved a larger ROC Area under Curve (AUC = 0.843) than HOMA-IR
indexes (0.640, 0.625 for HOMA1-IR, HOMA2-IR respectively) to screen for
Metabolic Syndrome. The cut-off values for MS were: TG/HDL-C ratio > 1.25
(sensitivity: 80%; specificity: 75%), HOMA1-IR > 4.59 (sensitivity: 58.7%;
specificity: 65.5%) and HOMA2-IR > 2.76 (sensitivity: 53.2%; specificity: 69.5%).
The results kept robust after stratified by gender, age group and pubertal stage.
DISCUSSION: TG/HDL-C ratio was a better indicator than the HOMA-IR to screen for
a positive diagnosis for MS. Furthermore, the TG/HDL-C ratio was superior to the
HOMA-IR indexes even after the control of possible confusions from the gender,
age group and puberty stage. CONCLUSION: TG/HDL-C ratio proved a better index
than HOMA-IR in screening for MS in obese children and adolescents. TG/HDL-C
ratio has a discriminatory power in detecting potential MS in the Chinese obese
pediatric population.
PMID- 26416209
TI - Effect of orthodontic brackets and different wires on radiofrequency heating and
magnetic field interactions during 3.0-T MRI.
PMID- 26416208
TI - MicroRNAs; easy and potent targets in optimizing therapeutic methods in
reparative angiogenesis.
AB - The age-related senescence of adult tissues is associated with the decreased
level of angiogenic capability and with the development of a degenerative disease
such as atherosclerosis which thereafter result in the deteriorating function of
multiple systems. Findings indicate that tissue senescence not only diminishes
repair processes but also promotes atherogenesis, serving as a double-edged sword
in the development and prognosis of ischaemia-associated diseases. Evidence
evokes microRNAs (miRNAs) as molecular switchers that underlie cellular events in
different tissues. Here, miRNAs would promote new potential targets for
optimizing therapeutic methods in blood flow recovery to the ischaemic area.
Effectively beginning an ischaemia therapy, a more characteristic of miRNA
changes in adult tissues is prerequisite and in the forefront. It may also be a
preliminary phase in treatment strategies by stem cell-based therapy.
PMID- 26416210
TI - Participation of dectin-1 receptor on NETs release against Paracoccidioides
brasiliensis: Role on extracellular killing.
AB - Paracoccidioides brasiliensis is a dimorphic fungus from the Paracoccidioides
genus, which is the causative agent of paracoccidioidomycosis, a chronic,
subacute or acute mycosis, with visceral and cutaneous involvement. This disease
that is acquired through inhalation primarily attacks the lungs but, can spread
to other organs. Phagocytic cells as neutrophils play an important role during
innate immune response against this fungus, but studies on antifungal activities
of these cells are scarce. In addition to their ability to eliminate pathogens by
phagocytosis and antimicrobial secretions, neutrophils can trap and kill
microorganisms by release of extracellular structures composed by DNA and
antimicrobial proteins, called neutrophil extracellular traps (NETs). Here, we
provide evidence that P. brasiliensis virulent strain (P. brasiliensis 18)
induces NETs release. These structures were well evidenced by scanning electron
microscopy, and specific NETs compounds such as histone, elastase and DNA were
shown by confocal microscopy. In addition, we have shown that dectin-1 receptor
is the main PRR to which fungus binds to induce NETS release. Fungi were ensnared
by NETs, denoting the role of these structures in confining the fungus, avoiding
dissemination. NETs were also shown to be involved in fungus killing, since
fungicidal activity detected before and mainly after neutrophils activation with
TNF-alpha, IFN-gamma and GM-CSF was significantly inhibited by cocultures
treatment with DNAse.
PMID- 26416211
TI - Suppression of IL-10 production by activated B cells via a cell contact-dependent
cyclooxygenase-2 pathway upregulated in IFN-gamma-treated mesenchymal stem cells.
AB - The immunoregulatory properties of mesenchymal stem cells (MSCs) have been well
documented in various models in vitro and in vivo. Furthermore, a population of
regulatory B cells (Bregs) that produce relatively high concentrations of IL-10
has been recently described. To study the relationship between MSCs and Bregs, we
analyzed the effects of MSCs on IL-10 production by lipopolysaccharide (LPS)
activated mouse B cells. The production of IL-10 by B cells remained preserved in
the presence of MSCs and was even significantly enhanced by IFN-gamma. However,
the production of IL-10 was strongly suppressed in cultures containing MSCs and
IFN-gamma. Preincubation of MSCs, but not of B cells, with IFN-gamma induced the
suppression of IL-10 secretion in cultures containing MSCs and B cells. The
supernatants from IFN-gamma-treated MSCs had no inhibitory effect, and the
suppression of IL-10 production was abrogated if the MSCs and B cells were
separated in a transwell system. Analysis of the gene expression of IFN-gamma- or
IFN-gamma and LPS-treated MSCs revealed a strong upregulation of genes for
indoleamine-2,3-dioxygenase (IDO), cyclooxygenase-2 (Cox-2) and programmed cell
death-ligand 1 (PD-L1). While the inhibition of IDO activity or the inclusion of
the neutralization monoclonal antibody anti-PD-L1 did not abrogate the
suppression, indomethacin, an inhibitor of Cox-2, completely inhibited the MSC
mediated suppression of IL-10 production. Accordingly, the production of IL-10 by
B cells was inhibited by exogenous prostaglandin E2. The results thus suggest
that IFN-gamma-treated MSCs strongly inhibit IL-10 production by activated B
cells by a mechanism requiring cell contact and involving the Cox-2 pathway.
PMID- 26416212
TI - Malignancy-associated pruritus.
AB - Malignancy-associated pruritus can be the result of a neoplasm's local effect on
tissue or due to the systemic reaction to malignancy. A systemic reaction to
malignancy has been termed 'paraneoplastic itch' and can be the first sign of an
underlying malignancy. Paraneoplastic itch is most commonly caused by
lymphoproliferative malignancies, and severity of itch correlates with stage of
disease in Hodgkin's lymphoma and polycythemia vera. Non-melanoma skin cancer is
the most common type of malignancy-associated pruritus, and recent data indicate
that pruritus is associated with more than one-third of non-melanoma skin
cancers. Cutaneous T-cell lymphomas (CTCL), particularly more advanced stages,
cause intractable pruritus and recent investigations into the pathophysiology of
CTCL-associated itch have implicated cyotokine interleukin-31 as a putative
mediator. Treatments that reduce itch in CTCL patients, such as histone
deacetylase inhibitors (HDACi), Mogamulizumab, a novel monoclonal antibody
against chemokine receptor type-4, and oral corticosteroids, have demonstrated a
correlation between their anti-pruritic effect and reduced serum levels of
interleukin-31.
PMID- 26416213
TI - Prenatal exposure to integerrimine N-oxide enriched butanolic residue from
Senecio brasiliensis affects behavior and striatal neurotransmitter levels of
rats in adulthood.
AB - Pyrrolizidine alkaloids (PAs) are toxins that are exclusively biosynthesized by
plants and are commonly present in foods and herbs. PAs are usually associated
with poisoning events in livestock and human beings. The aim of the present study
was to evaluate the behavioral and neurochemical effects of prenatal exposure to
PA integerrimine N-oxide of rats in adulthood. Pregnant Wistar rats received
integerrimine N-oxide from the butanolic residue of Senecio brasiliensis by
gavage on gestational days 6-20 at doses of 3, 6 and 9 mg/kg. During adulthood of
the offspring, the following behavioral tests were performed: open-field, plus
maze, forced swimming, catalepsy and stereotypy. Histological analyses and
monoamine levels were measured. Male offspring from dams that were exposed to 9
mg/kg showed an increase in locomotion in the open-field test, an increased
frequency of entries and time spent in open arms in elevated plus-maze test, as
well as decreased swimming time. In the female offspring from dams that were
exposed to 9 mg/kg, there was an increased time of climbing in forced swimming
and intensity of stereotyped behavior. The histological study indicates an
increase in the number of multinucleated cells in the liver (6 and 9 mg/kg). In
neurotransmitter analysis, specifically in the striatum, we observed change in
dopamine and serotonin levels in the middle dose. Thus, our results indicate that
prenatal exposure to integerrimine N-oxide changed behavior in adulthood and
neurotransmitter levels in the striatum. Our results agree with previous studies,
which showed that integerrimine N-oxide impaired physical and neurobehavioral
development in childhood that can persist until adulthood.
PMID- 26416214
TI - Rapid and Effective Virucidal Activity of Povidone-Iodine Products Against Middle
East Respiratory Syndrome Coronavirus (MERS-CoV) and Modified Vaccinia Virus
Ankara (MVA).
AB - INTRODUCTION: Since the first case of Middle East Respiratory Syndrome
coronavirus (MERS-CoV) infection was reported in 2012, the virus has infected
more than 1300 individuals in 26 countries, and caused more than 480 deaths.
Human-to-human transmission requires close contact, and has typically occurred in
the healthcare setting. Improved global awareness, together with improved hygiene
practices in healthcare facilities, has been highlighted as key strategies in
controlling the spread of MERS-CoV. This study tested the in vitro efficacy of
three formulations of povidone iodine (PVP-I: 4% PVP-I skin cleanser, 7.5% PVP-I
surgical scrub, and 1% PVP-I gargle/mouthwash) against a reference virus
(Modified vaccinia virus Ankara, MVA) and MERS-CoV. METHODS: According to
EN14476, a standard suspension test was used to assess virucidal activity against
MVA and large volume plating was used for MERS-CoV. All products were tested
under clean (0.3 g/L bovine serum albumin, BSA) and dirty conditions (3.0 g/L BSA
+ 3.0 mL/L erythrocytes), with application times of 15, 30, and 60 s for MVA, and
15 s for MERS-CoV. The products were tested undiluted, 1:10 and 1:100 diluted
against MVA, and undiluted against MERS-CoV. RESULTS: A reduction in virus titer
of >=4 log10 (corresponding to an inactivation of >=99.99%) was regarded as
evidence of virucidal activity. This was achieved versus MVA and MERS-CoV, under
both clean and dirty conditions, within 15 s of application of each undiluted PVP
I product. CONCLUSION: These data indicate that PVP-I-based hand wash products
for potentially contaminated skin, and PVP-I gargle/mouthwash for reduction of
viral load in the oral cavity and the oropharynx, may help to support hygiene
measures to prevent transmission of MERS-CoV. FUNDING: Mundipharma Research GmbH
& Co.
PMID- 26416215
TI - Sebastien Sasseville: dreaming with type 1 diabetes.
PMID- 26416216
TI - Access to primary care in Italy: time for a shake-up?
PMID- 26416217
TI - QSAR and molecular docking studies on oxindole derivatives as VEGFR-2 tyrosine
kinase inhibitors.
AB - The three-dimensional quantitative structure-activity relationships (3D-QSAR)
were established for 30 oxindole derivatives as vascular endothelial growth
factor receptor-2 (VEGFR-2) tyrosine kinase inhibitors by using comparative
molecular field analysis (CoMFA) and comparative similarity indices analysis
comparative molecular similarity indices analysis (CoMSIA) techniques. With the
CoMFA model, the cross-validated value (q(2)) was 0.777, the non-cross-validated
value (R(2)) was 0.987, and the external cross-validated value ([Formula: see
text]) was 0.72. And with the CoMSIA model, the corresponding q(2), R(2) and
[Formula: see text] values were 0.710, 0.988 and 0.78, respectively. Docking
studies were employed to bind the inhibitors into the active site to determine
the probable binding conformation. The binding mode obtained by molecular docking
was in good agreement with the 3D-QSAR results. Based on the QSAR models and the
docking binding mode, a set of new VEGFR-2 tyrosine kinase inhibitors were
designed, which showed excellent predicting inhibiting potencies. The result
revealed that both QSAR models have good predictive capability to guide the
design and structural modification of homologic compounds. It is also helpful for
further research and development of new VEGFR-2 tyrosine kinase inhibitors.
PMID- 26416218
TI - Development: Maternal hyperglycaemia affects cardiac development.
PMID- 26416221
TI - Cardiovascular endocrinology: High-intensity interval training benefits patients
with T2DM.
PMID- 26416220
TI - Diabetes: Metformin and renal insufficiency-is 45, or even 30, the new 60?
PMID- 26416219
TI - Scope and limitations of iodothyronine deiodinases in hypothyroidism.
AB - The coordinated expression and activity of the iodothyronine deiodinases regulate
thyroid hormone levels in hypothyroidism. Once heralded as the pathway
underpinning adequate thyroid-hormone replacement therapy with levothyroxine, the
role of these enzymes has come into question as they have been implicated in both
an inability to normalize serum levels of tri-iodothyronine (T3) and the
incomplete resolution of hypothyroid symptoms. These observations, some of which
were validated in animal models of levothyroxine monotherapy, challenge the
paradigm that tissue levels of T3 and thyroid-hormone signalling can be fully
restored by administration of levothyroxine alone. The low serum levels of T3
observed among patients receiving levothyroxine monotherapy occur as a
consequence of type 2 iodothyronine deiodinase (DIO2) in the hypothalamus being
fairly insensitive to ubiquitination. In addition, residual symptoms of
hypothyroidism have been linked to a prevalent polymorphism in the DIO2 gene that
might be a risk factor for neurodegenerative disease. Here, we discuss how these
novel findings underscore the clinical importance of iodothyronine deiodinases in
hypothyroidism and how an improved understanding of these enzymes might translate
to therapeutic advances in the care of millions of patients with this condition.
PMID- 26416222
TI - Evidence that smooth pursuit velocity, not eye position, modulates alpha and beta
oscillations in human middle temporal cortex.
AB - Suppression of 5-25 Hz oscillations have been observed in MT+ during pursuit eye
movements, suggesting oscillations that play a role in oculomotor control and/or
the integration of extraretinal signals during pursuit. The amplitude of these
rhythms appears to covary with head-centered eye position, but an alternative is
that they depend on a velocity signal that lags the movement of the eyes. To
investigate, we explored how alpha and beta amplitude changes related to ongoing
eye movement depended on pursuit at different eccentricities. The results
revealed largely identical patterns of modulation in the alpha and beta
amplitude, irrespective of the eccentricity at which the pursuit eye movement was
performed. The signals we measured therefore do not depend on head-centered
position. A second experiment was designed to investigate whether the alpha and
beta oscillations depended on the direction of pursuit, as opposed to just speed.
We found no evidence that alpha or beta oscillations depended on direction, but
there was a significant effect of eye speed on the magnitude of the beta
suppression. This suggests distinct functional roles for alpha and beta
suppression in pursuit behavior.
PMID- 26416223
TI - Case report: clear cell hidradenocarcinoma of the nail bed.
PMID- 26416224
TI - UN adopts new global health targets to supersede the millennium goals.
PMID- 26416225
TI - Tobacco smoke exposure and multiplexed immunoglobulin E sensitization in
children: a population-based study.
AB - BACKGROUND: Although there is evidence that exposure to tobacco smoke is harmful
to children's respiratory health, the effects of tobacco smoke exposure on the
regulation of immunoglobulin E (IgE)-mediated immune responses to specific
allergens remain unclear. This study aimed to investigate the relationship
between objectively assessed tobacco smoke exposure and specific IgE profiles for
a broad spectrum of allergens in a population setting. METHODS: Children aged 5
18 years (N = 1315) were assessed using serum cotinine measurement and microarray
based multiplexed detection of specific IgE against 40 allergens. RESULTS: Serum
cotinine levels were positively associated with sensitization to foods (adjusted
odds ratio [AOR] = 4.95; 95% CI: 1.59-15.34), cockroaches (AOR = 3.77; 95% CI:
1.49-9.51), and pollen (AOR = 2.84; 95% CI: 1.20-6.73) while the association was
borderline significant for animals (AOR = 2.53; 95% CI: 0.92-6.93). No
associations were found for sensitization against mites, mold, and latex. When
considering the degree of allergic sensitization, serum cotinine levels were
positively correlated to the number of sensitization to cockroaches (P = 0.004),
pollen (P = 0.006), and foods (P < 0.001), with statistically significant
positive dose-response relationships (all P < 0.01). Similar results were
observed when summing up specific IgE concentrations for the aforementioned
allergen categories. CONCLUSIONS: The association between tobacco smoke exposure
and IgE sensitization to environmental allergens varies for different allergens
among children. This study demonstrates that elevated serum cotinine levels are
significantly associated with IgE sensitization to cockroaches, grass pollen, and
certain foods, with potential dose-dependent relationships.
PMID- 26416226
TI - Beta Cells Secrete Significant and Regulated Levels of Insulin for Long Periods
when Seeded onto Acellular Micro-Scaffolds.
AB - The aim of this work is to obtain significant and regulated insulin secretion
from human beta cells ex vivo. Long-term culture of human pancreatic islets and
attempts at expanding human islet cells normally result in loss of beta-cell
phenotype. We propose that to obtain proper ex vivo beta cell function, there is
a need to develop three-dimensional structures that mimic the natural islet
tissue microenvironment. We here describe the preparation of endocrine micro
pancreata (EMPs) that are made up of acellular organ-derived micro-scaffolds
seeded with human intact or enzymatically dissociated islets. We show that EMPs
constructed by seeding whole islets, freshly enzymatically-dissociated islets or
even dissociated islets grown first in standard monolayer cultures express high
levels of key beta-cell specific genes and secrete quantities of insulin per cell
similar to freshly isolated human islets in a glucose-regulated manner for more
than 3 months in vitro.
PMID- 26416227
TI - Spontaneous shape transition of thin films into ZnO nanowires with high
structural and optical quality.
AB - ZnO nanowires are usually formed by physical and chemical deposition techniques
following the bottom-up approach consisting in supplying the reactants on a
nucleation surface heated at a given temperature. We demonstrate an original
alternative approach for the formation of ZnO nanowire arrays with high
structural and optical quality, which is based on the spontaneous transformation
of a ZnO thin film deposited by sol-gel process following a simple annealing. The
development of these ZnO nanowires occurs through successive shape transitions,
including the intermediate formation of pyramid-shaped islands. Their nucleation
under near-equilibrium conditions is expected to be governed by thermodynamic
considerations via the total free energy minimization related to the nanowire
shape. It is further strongly assisted by the drastic reordering of the matter
and by recrystallization phenomena through the massive transport of zinc and
oxygen atoms towards the localized growth areas. The spontaneous shape transition
process thus combines the easiness and low-cost of sol-gel process and simple
annealing with the assets of the vapor phase deposition techniques. These
findings cast a light on the fundamental mechanisms driving the spontaneous
formation of ZnO nanowires and, importantly, reveal the great technological
potential of the spontaneous shape transition process as a promising alternative
approach to the more usual bottom-up approach.
PMID- 26416228
TI - Lower glycolysis carries a higher flux than any biochemically possible
alternative.
AB - The universality of many pathways of core metabolism suggests a strong role for
evolutionary selection, but it remains unclear whether existing pathways have
been selected from a large or small set of biochemical possibilities. To address
this question, we construct in silico all possible biochemically feasible
alternatives to the trunk pathway of glycolysis and gluconeogenesis, one of the
most highly conserved pathways in metabolism. We show that, even though a large
number of alternative pathways exist, the alternatives carry lower flux than the
real pathway under typical physiological conditions. We also find that if
physiological conditions were different, different pathways could outperform
those found in nature. Together, our results demonstrate how thermodynamic and
biophysical constraints restrict the biochemical alternatives that are open to
evolution, and suggest that the existing trunk pathway of glycolysis and
gluconeogenesis may represent a maximal flux solution.
PMID- 26416229
TI - The challenges of introducing routine G6PD testing into radical cure: a workshop
report.
AB - The only currently available drug that effectively removes malaria hypnozoites
from the human host is primaquine. The use of 8-aminoquinolines is hampered by
haemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficient
individuals. Recently a number of qualitative and a quantitative rapid diagnostic
test (RDT) format have been developed that provide an alternative to the current
standard G6PD activity assays. The WHO has recently recommended routine testing
of G6PD status prior to primaquine radical cure whenever possible. A workshop was
held in the Philippines in early 2015 to discuss key challenges and knowledge
gaps that hinder the introduction of routine G6PD testing. Two point-of-care
(PoC) test formats for the measurement of G6PD activity are currently available:
qualitative tests comparable to malaria RDT as well as biosensors that provide a
quantitative reading. Qualitative G6PD PoC tests provide a binomial test result,
are easy to use and some products are comparable in price to the widely used
fluorescent spot test. Qualitative test results can accurately classify
hemizygous males, heterozygous females, but may misclassify females with
intermediate G6PD activity. Biosensors provide a more complex quantitative
readout and are better suited to identify heterozygous females. While associated
with higher costs per sample tested biosensors have the potential for broader use
in other scenarios where knowledge of G6PD activity is relevant as well. The
introduction of routine G6PD testing is associated with additional costs on top
of routine treatment that will vary by setting and will need to be assessed prior
to test introduction. Reliable G6PD PoC tests have the potential to play an
essential role in future malaria elimination programmes, however require an
improved understanding on how to best integrate routine G6PD testing into
different health settings.
PMID- 26416230
TI - Melatonin treatment during the incubation of sensitization attenuates
methamphetamine-induced locomotor sensitization and MeCP2 expression.
AB - Behavior sensitization is a long-lasting enhancement of locomotor activity after
exposure to psychostimulants. Incubation of sensitization is a phenomenon of
remarkable augmentation of locomotor response after withdrawal and reflects
certain aspects of compulsive drug craving. However, the mechanisms underlying
these phenomena remain elusive. Here we pay special attention to the incubation
of sensitization and suppose that the intervention of this procedure will finally
decrease the expression of sensitization. Melatonin is an endogenous hormone
secreted mainly by the pineal gland. It is effective in treating sleep disorder,
which turns out to be one of the major withdrawal symptoms of methamphetamine
(MA) addiction. Furthermore, melatonin can also protect neuronal cells against MA
induced neurotoxicity. In the present experiment, we treated mice with low dose
(10mg/kg) of melatonin for 14 consecutive days during the incubation of
sensitization. We found that melatonin significantly attenuated the expression of
sensitization. In contrast, the vehicle treated mice showed prominent enhancement
of locomotor activity after incubation. MeCP2 expression was also elevated in the
vehicle treated mice and melatonin attenuated its expression. Surprisingly,
correlation analysis suggested significant correlation between MeCP2 expression
in the nucleus accumbens (NAc) and locomotion in both saline control and vehicle
treated mice, but not in melatonin treated ones. MA also induced MeCP2 over
expression in PC12 cells. However, melatonin failed to reduce MeCP2 expression in
vitro. Our results suggest that melatonin treatment during the incubation of
sensitization attenuates MA-induced expression of sensitization and decreases
MeCP2 expression in vivo.
PMID- 26416231
TI - Editorial: Harmful and Beneficial Effect of Aspirin on Gastrointestinal Tract.
PMID- 26416232
TI - Editorial: New Trends in Pharmaceutical Nanotechnology.
PMID- 26416233
TI - Dairy products consumption and metabolic syndrome in adults: systematic review
and meta-analysis of observational studies.
AB - The association of dairy products consumption with risk of metabolic syndrome
(MetS) has been inconsistently reported in observational studies. A systematic
review and meta-analysis of published observational studies was conducted to
quantitatively evaluate this association. Relevant studies were identified by
searching PubMed and EMBASE databases and by carefully checking the
bibliographies of retrieved full reports and related reviews. Eligible studies
were observational studies that investigated the association between dairy
products consumption and risk of MetS in adults, with risk estimates available.
Random-effects model was assigned to calculate the summary risk estimates. The
final analysis included 15 cross-sectional studies, one case-control study and
seven prospective cohort studies. Higher dairy consumption significantly reduced
MetS by 17% in the cross-sectional/case-control studies (odds ratio = 0.83, 95%
confidence interval [CI], 0.73-0.94), and by 14% (relative risk [RR] = 0.86, 95%
CI, 0.79-0.92) in cohort studies. The inverse dairy-MetS association was
consistent in subgroup and sensitivity analyses. The dose-response analysis of
the cohort studies conferred a significant 6% (RR = 0.94, 95% CI, 0.90-0.98)
reduction in the risk of MetS for each increment in dairy consumption of one
serving/d. No significant publication bias was observed. Our findings suggest an
inverse dose-response relationship between dairy consumption and risk of MetS.
PMID- 26416235
TI - Visible-light-promoted chloramination of olefins with N-chlorosulfonamide as both
nitrogen and chlorine sources.
AB - A visible-light-promoted chloramination of olefins is reported. N
Chlorosulfonamides serve as both nitrogen and chlorine sources. These reactions
provide a simple, efficient, regioselective, and atom-economical method for the
preparation of vicinal haloamine derivatives under mild reaction conditions. A
variety of olefins were tolerated, and chloramination products were obtained in
good yields.
PMID- 26416234
TI - Meaning in life and perceived quality of life in Switzerland: results of a
representative survey in the German, French and Italian regions.
AB - BACKGROUND: The concept of meaning in life (MIL) has become a central one in
recent years, particularly in psycho-oncology and palliative care. The Schedule
for Meaning in Life Evaluation (SMILE) has been developed to allow individuals to
choose the life areas that they consider to be important for their own MIL. This
approach relates to the "World Health Organisation" definition of quality of life
(QOL) as an individual's perception of his own position. The aims of this study
were (i) to assess MIL in a representative sample of the Swiss population
according to the three linguistic regions and (ii) to evaluate whether MIL
constitutes a significant determinant of the perceived QOL. METHODS: A telephone
survey of the Swiss population, performed by a professional survey company, was
conducted between November and December 2013. The interview included the SMILE,
perceived QOL (0-10) and health status (1-5), and various sociodemographic
variables. In the SMILE, an index of weighting (IOW, 20-100), an index of
satisfaction (IOS, 0-100), and a total SMILE index (IOWS, 0-100) are calculated
from the areas mentioned by the participants as providing MIL. RESULTS: Among the
6671 telephonic contacts realized, 1015 (15%) participants completed the survey:
405 French, 400 German and 210 Italian participants. "Family" (80.2%),
"occupation/work" (51%), and "social relations" (43.3%) were the most cited MIL
relevant categories. Italian participants listed "health" more frequently than
German and French participants (50.4% vs 31.5% and 24.8% respectively, chi(2) =
12.229, p = .002). Age, gender, education, employment, and marital status
significantly influenced either the MIL scores or the MIL-relevant categories.
Linear regression analyses indicate that 24.3% of the QOL variance (p = .000) is
explained by health status (B = .609, IC = .490-.728, p = .000), MIL (B = .034,
IC = .028-.041, p = .000) and socioeconomic status (F = 11.01, p = .000).
CONCLUSION: The major finding of our analysis highlights the positive and
significant influence of MIL on the perceived QOL in a representative sample of a
general, multilingual and multicultural population. This result indicates that
the existential dimension is not only determinant for QOL in some critical life
events, as shown e.g. in psycho-oncology and palliative care, but also in
everyday life.
PMID- 26416236
TI - Rheological and microstructural properties of the chia seed polysaccharide.
AB - Chia seed polysaccharide (CSP) was extracted from chia (Salvia hispanica) seeds,
and its rheological and microstructural properties in aqueous solutions were
studied. CSP solution exhibited Newtonian and shear thinning flow patterns
depending on shear rate when the concentration was <=0.06% (w/v). CSP solutions
at concentrations >0.06% (w/v) exhibited strong shear thinning behaviour within
the shear rate tested (0.001-300s(-1)). The transition from dilute to semi-dilute
regime occurred at a critical concentration (C*) of 0.03gdL(-1). The intrinsic
viscosity was high (~16dLg(-1)) and concentration dependence of zero shear
viscosity in the semi-dilute regime followed eta0?C(2.7) relationship. The
storage modulus (G') was higher than the loss modulus (G") at all experimental
frequencies and their frequency dependence was negligible at all tested
concentrations. Apparent shear viscosity was smaller than dynamic complex
viscosity at equivalent values of deformation and G' varied with the square of
concentration indicating a gel-like behaviour in CSP solutions within 0.02-3.0%
(w/v) concentrations. Controlled acid hydrolysis of purified CSP yielded various
low molecular fractions with fairly uniform polydispersity giving a Mark-Houwink
Sakurada relationship of intrinsic viscosity equaling to 1.52*10(-4) (molecular
weight)(0.803) (dLg(-1)).
PMID- 26416237
TI - Structural studies of Helix aspersa agglutinin complexed with GalNAc: A lectin
that serves as a diagnostic tool.
AB - Lectins belong to a differentiated group of proteins known to possess sugar
binding properties. Due to this fact, they are interesting research targets in
medical diagnostics. Helix aspersa agglutinin (HAA) is a lectin that recognizes
the epitopes containing alpha-d-N-acetylgalactosamine (GalNAc), which is present
at the surface of metastatic cancer cells. Although several reports have already
described the use of HAA as a diagnostic tool, this protein was not characterized
on the molecular level. Here, we present for the first time the structural
information about lectin isolated from mucus of Helix aspersa (garden snail). The
amino acid sequence of this agglutinin was determined by Edman degradation and
tertiary as well as quaternary structure by X-ray crystallography. The high
resolution crystal structure (1.38A) and MALDI-TOF mass spectrometry analysis
provide the detailed information about a large part of the HAA natural glycan
chain. The topology of the GalNAc binding cleft and interaction with lectin are
very well defined in the structure and fully confirmed by STD HSQC NMR
spectroscopy. Together, this provides structural clues regarding HAA specificity
and opens possibilities to rational modifications of this important diagnostic
tool.
PMID- 26416238
TI - Binding interaction between rice glutelin and amylose: Hydrophobic interaction
and conformational changes.
AB - The interaction of rice glutelin (RG) with amylose was characterized by
spectroscopic and molecular docking studies. The intrinsic fluorescence of RG
increased upon the addition of amylose. The binding sites, binding constant and
thermodynamic features indicated that binding process was spontaneous and the
main driving force of the interaction was hydrophobic interaction. The surface
hydrophobicity of RG decreased with increasing amount of amylose. Furthermore,
synchronous fluorescence and circular dichroism (CD) spectra provided data
concerning conformational and micro-environmental changes of RG. With the
concentration of amylose increasing, the polarity around the tyrosine residues
increased while the hydrophobicity decreased. Alteration of protein conformation
was observed with increasing of alpha-helix and reducing of beta-sheet. Finally,
a visual representation of two binding sites located in the amorphous area of RG
was presented by molecular modeling studies.
PMID- 26416239
TI - Kinetics of Spanish broom peroxidase obeys a Ping-Pong Bi-Bi mechanism with
competitive inhibition by substrates.
AB - In plants, adverse conditions often induce an increase in reactive oxygen species
(ROS) such as hydrogen peroxide (H2O2). H2O2 is reduced to water, and thus
becomes detoxified by enzymes such as Cytisus multiflorus peroxidase (CMP). Here,
the steady-state kinetics of the H2O2-supported oxidation of different organic
substrates by CMP was investigated. Analysis of the initial rates vs. H2O2 and
reducing substrate concentrations proved to be consistent with a substrate
inhibited Ping-Pong Bi-Bi reaction mechanism. The phenomenological approach
expresses the peroxidase Ping-Pong mechanism in the form of the Michaelis-Menten
equation and affords an interpretation of the effects in terms of the kinetic
parameters [Formula: see text] , [Formula: see text] , kcat, [Formula: see text]
, [Formula: see text] and of the microscopic rate constants, k1 and k3, of the
shared three-step catalytic cycle of peroxidases.
PMID- 26416240
TI - Emerging patterns of genetic variation in the New Zealand endemic scallop Pecten
novaezelandiae.
AB - Both historical and contemporary processes influence the genetic structure of
species, but the relative roles of such processes are still difficult to access.
Population genetic studies of species with recent evolutionary histories such as
the New Zealand endemic scallop Pecten novaezelandiae (<1 Ma) permit testing of
the effects of recent processes affecting gene flow and shaping genetic
structure. In addition, studies encompassing the entire distributional range of
species can provide insight into colonization processes. Analyses of genetic
variation in P. novaezelandiae (952 individuals from 14 locations, genotyped at
10 microsatellite loci) revealed a weak but significant regional structure across
the distributional range of the species, as well as latitudinal gradients of
genetic diversity and differentiation: estimates of migration rates supported
these patterns. Our results suggest that the observed genetic structure and
latitudinal gradients reflect a stepping-stone model of colonization (north to
south) and emerging divergence of populations as a result of ongoing limitations
to gene flow and insufficient time to reach migration-drift equilibrium. The low
levels of interpopulation and interregional genetic differentiation detected over
hundreds of kilometres reflect the recent evolutionary history of P.
novaezelandiae and stand in contrast to patterns reported for other evolutionary
older species at the same spatial scale. The outcomes of this study contribute to
a better understanding of evolutionary processes influencing the genetic
variation of species and provide vital information on the genetic structure of P.
novaezelandiae.
PMID- 26416241
TI - Multiple violence victimisation associated with sexual ill health and sexual risk
behaviours in Swedish youth.
AB - OBJECTIVES: To address the associations between emotional, physical and sexual
violence, specifically multiple violence victimisation, and sexual ill health and
sexual risk behaviours in youth, as well as possible gender differences. METHODS:
A cross-sectional population-based survey among sexually experienced youth using
a questionnaire with validated questions on emotional, physical, and sexual
violence victimisation, sociodemographics, health risk behaviours, and sexual ill
health and sexual risk behaviours. Proportions, unadjusted/adjusted odds ratios
(ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: The
participants comprised 1192 female and 1021 male students aged 15 to 22 years.
The females had experienced multiple violence (victimisation with two or three
types of violence) more often than the males (21% vs. 16%). The associations
between multiple violence victimisation and sexual ill health and sexual risk
behaviours were consistent for both genders. Experience of/involvement in
pregnancy yielded adjusted ORs of 2.4 (95% CI 1.5-3.7) for females and 2.1 (95%
CI 1.3-3.4) for males, and early age at first intercourse 2.2 (95% CI 1.6-3.1)
for females and 1.9 (95% CI 1.2-3.0) for males. No significantly raised adjusted
ORs were found for non-use of contraceptives in young men or young women, or for
chlamydia infection in young men. CONCLUSIONS: Several types of sexual ill health
and sexual risk behaviours are strongly associated with multiple violence
victimisation in both genders. This should be taken into consideration when
counselling young people and addressing their sexual and reproductive health.
PMID- 26416242
TI - Avian Podocytes, Which Lack Nephrin, Use Adherens Junction Proteins at
Intercellular Junctions.
AB - Nephrin, a major intercellular junction (ICJ) molecule of mammalian podocytes in
the renal glomerulus, is absent in the avian genome. We hypothesized that birds
use ICJ molecules other than nephrin in their podocytes. Therefore, in the
present study, we examined the possible involvement of adherens junction (AJ)
proteins in the ICJs of avian podocytes. We found the AJ proteins N-cadherin and
alpha- and beta-catenins in podocytes of quail and chickens but not in those of
rats, pigs or humans. The AJ proteins were prominent in avian glomerulus-rich
fractions in immunoblot analyses, and in immunofluorescence microscopy analyses,
they were localized along glomerular capillary walls appearing in at least two
staining patterns: weakly diffuse and distinctly granular. Immunoelectron
microscopy demonstrated that the significant accumulation of immunogold particles
for the AJ proteins were especially evident in avian slit diaphragms and AJs.
Furthermore, N-cadherin was found to be expressed in all nephron cells in the
early developmental stage but became confined to podocytes during maturation.
These results indicate that avian slit diaphragms clearly express AJ proteins as
compared with that in the mammal-where AJ proteins are suppressed to an extremely
low level-and that avian podocytes are interconnected by AJs per se in addition
to slit diaphragms.
PMID- 26416243
TI - Long-Term Administration of High-Fat Diet Corrects Abnormal Bone Remodeling in
the Tibiae of Interleukin-6-Deficient Mice.
AB - In this study, we aimed to evaluate the influence of diet-induced obesity on IL-6
deficiency-induced bone remodeling abnormality. Seven-week-old IL-6(-/-) mice and
their wild type (WT) littermates were fed a standard diet (SD) or high-fat diet
(HFD) for 25 weeks. Lipid formation and bone metabolism in mice tibiae were
investigated by histochemical analysis. Both IL-6(-/-) and WT mice fed the HFD
showed notable body weight gain, thickened cortical bones, and adipose
accumulation in the bone marrow. Notably, the HFD normalized the bone phenotype
of IL-6(-/-) mice to that of their WT counterpart, as characterized by a decrease
in bone mass and the presence of an obliquely arranged, plate-like morphology in
the trabecular bone. Alkaline phosphatase and osteocalcin expressions were
attenuated in both genotypes after HFD feeding, especially for the IL-6(-/-)
mice. Meanwhile, tartrate-resistant acid phosphatase staining was inhibited,
osteoclast apoptosis rate down-regulated (revealed by TUNEL assay), and the
proportion of cathepsin K (CK)-positive osteoclasts significantly increased in IL
6(-/-) mice on a HFD as compared with IL-6(-/-) mice on standard chow. Our
results demonstrate that HFD-induced obesity reverses IL-6 deficiency-associated
bone metabolic disorders by suppressing osteoblast activity, upregulating
osteoclastic activity, and inhibiting osteoclast apoptosis.
PMID- 26416245
TI - The value of forceps biopsy and core needle biopsy in prediction of pathologic
complete remission in locally advanced rectal cancer treated with neoadjuvant
chemoradiotherapy.
AB - Patients with pathological complete remission (pCR) after treated with
neoadjuvant chemoradiotherapy (nCRT) have better long-term outcome and may
receive conservative treatments in locally advanced rectal cancer (LARC). The
study aimed to evaluate the value of forceps biopsy and core needle biopsy in
prediction of pCR in LARC treated with nCRT. In total, 120 patients entered this
study. Sixty-one consecutive patients received preoperative forceps biopsy during
endoscopic examination. Ex vivo core needle biopsy was performed in resected
specimens of another 43 consecutive patients. The accuracy for ex vivo core
needle biopsy was significantly higher than forceps biopsy (76.7% vs. 36.1%; p <
0.001). The sensitivity for ex vivo core needle biopsy was significantly lower in
good responder (TRG 3) than poor responder (TRG <= 2) (52.9% vs. 94.1%; p =
0.017). In vivo core needle biopsy was further performed in 16 patients with good
response. Eleven patients had residual cancer cells in final resected specimens,
among whom 4 (36.4%) patients were biopsy positive. In conclusion, routine
forceps biopsy was of limited value in identifying pCR after nCRT. Although core
needle biopsy might further identify a subset of patients with residual cancer
cells, the accuracy was not substantially increased in good responders.
PMID- 26416246
TI - Visualizing the antivascular effect of bortezomib on the hypoxic tumor
microenvironment.
AB - Bortezomib, a novel proteasome inhibitor, has been approved for treating multiple
myeloma and mantle cell lymphoma and studied pre-clinically and clinically for
solid tumors. Preferential cytotoxicity of bortezomib was found toward hypoxic
tumor cells and endothelial cells in vitro. The purpose of this study is to
investigate the role of a pretreatment hypoxic tumor microenvironment on the
effects of bortezomib in vitro and ex vivo, and explore the feasibility of
dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to noninvasively
evaluate the biological effects of bortezomib. It was shown in vitro by Western
blot, flow cytometry, and ELISA that bortezomib accumulated HIF-1alpha in non
functional forms and blocks its hypoxia response in human colorectal cancer cell
lines. Ex vivo experiments were performed with fluorescent immunohistochemical
staining techniques using multiple endogenous and exogenous markers to identify
hypoxia (pimonidazole, HRE-TKeGFP), blood flow/permeability (Hoechst 33342),
micro-vessels (CD31 and SMA), apoptosis (cleaved caspase 3) and hypoxia response
(CA9). After bortezomib administration, overall apoptosis index was significantly
increased and blood perfusion was dramatically decreased in tumor xenografts.
More importantly, apoptosis signals were found preferentially located in moderate
and severe pretreatment hypoxic regions in both tumor and endothelial cells.
Meanwhile, DCE MRI examinations showed that the tumor blood flow and permeability
decreased significantly after bortezomib administration. The present study
revealed that bortezomib reduces tumor hypoxia response and blood perfusion,
thus, presenting antivascular properties. It will be important to determine the
hypoxic/perfusion status pre- and during treatment at further translational
studies.
PMID- 26416244
TI - Targeting of cytosolic phospholipase A2alpha impedes cell cycle re-entry of
quiescent prostate cancer cells.
AB - Cell cycle re-entry of quiescent cancer cells has been proposed to be involved in
cancer progression and recurrence. Cytosolic phospholipase A2alpha (cPLA2alpha)
is an enzyme that hydrolyzes membrane glycerophospholipids to release arachidonic
acid and lysophospholipids that are implicated in cancer cell proliferation. The
aim of this study was to determine the role of cPLA2alpha in cell cycle re-entry
of quiescent prostate cancer cells. When PC-3 and LNCaP cells were rendered to a
quiescent state, the active form of cPLA2alpha with a phosphorylation at Ser505
was lower compared to their proliferating state. Conversely, the phospho
cPLA2alpha levels were resurgent during the induction of cell cycle re-entry.
Pharmacological inhibition of cPLA2alpha with Efipladib upon induction of cell
cycle re-entry inhibited the re-entry process, as manifested by refrained DNA
synthesis, persistent high proportion of cells in G0/G1 and low percentage of
cells in S and G2/M phases, together with a stagnant recovery of Ki-67
expression. Simultaneously, Efipladib prohibited the emergence of Skp2 while
maintained p27 at a high level in the nuclear compartment during cell cycle re
entry. Inhibition of cPLA2alpha also prevented an accumulation of cyclin D1/CDK4,
cyclin E/CDK2, phospho-pRb, pre-replicative complex proteins CDC6, MCM7, ORC6 and
DNA synthesis-related protein PCNA during induction of cell cycle re-entry.
Moreover, a pre-treatment of the prostate cancer cells with Efipladib during
induction of cell cycle re-entry subsequently compromised their tumorigenic
capacity in vivo. Hence, cPLA2alpha plays an important role in cell cycle re
entry by quiescent prostate cancer cells.
PMID- 26416247
TI - LGR5 is associated with tumor aggressiveness in papillary thyroid cancer.
AB - PURPOSE: Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a
cancer stem cell marker and a down-stream target in Wnt/beta-catenin signaling.
In human papillary thyroid cancer (PTC), over activation of Wnt/beta-catenin has
been associated with tumor aggressiveness. PATIENTS AND METHODS: Using
established human cell lines (TPC-1, KTC-1, Nthy-ori-3-1), we report LGR5 and R
spondin (RSPO1-3) overexpression in PTC and manipulate LGR5 and Wnt/beta-catenin
signaling via both pharmacologic and genetic interventions. We test the
association of LGR5 tumor expression with markers of PTC aggressiveness using a
Discovery Cohort (n = 26 patients) and a Validation Cohort (n = 157 patients).
Lastly, we explore the association between LGR5 and the BRAFV600E mutation (n =
33 patients). RESULTS: Our results reveal that LGR5 and its ligand, RSPO, are
overexpressed in human PTC, whereby Wnt/beta-catenin signaling regulates LGR5
expression and promotes cellular migration. In two separate cohorts of patients,
LGR5 and RSPO2 were associated with markers of tumor aggressiveness including:
lymph node metastases, vascular invasion, increased tumor size, aggressive
histology, advanced AJCC TNM stage, microscopic extra thyroidal extension,
capsular invasion, and macroscopic invasion. As a biomarker, LGR5 positivity
predicts lymph node metastasis with 95.5% sensitivity (95% CI 88.8%-98.7%) and
61% specificity (95% CI: 48.4%-72.4%) and has a negative predictive value (NPV)
of 91.3% (95% CI 79.2%-97.5%) for lymph node metastatic disease. In human PTC,
LGR5 is also strongly associated with the BRAFV600E mutation (p = 0.005).
CONCLUSION: We conclude that overexpression of LGR5 is associated with markers of
tumor aggressiveness in human PTC. LGR5 may serve as a future potential biomarker
for patient risk stratification and loco regional metastases in PTC.
PMID- 26416248
TI - RhoGDI deficiency induces constitutive activation of Rho GTPases and COX-2
pathways in association with breast cancer progression.
AB - Rho GDP Dissociation Inhibitor (RhoGDI) is a key regulator of Rho GTPases. Here
we report that loss of RhoGDI significantly accelerated xenograft tumor growth of
MDA-MB-231 cells in animal models. At the molecular level, RhoGDI depletion
resulted in constitutive activation of Rho GTPases, including RhoA, Cdc42, and
Rac1. This was accompanied by Rho GTPase translocation from the cytosol to
membrane compartments. Notably, COX-2 protein levels, mRNA expression, and
biological activity were markedly increased in RhoGDI-deficient cells. The
upregulated expression of COX-2 was directly associated with increased Rho GTPase
activity. Further, we assessed the expression level of RhoGDI protein in breast
tumor specimens (n = 165) by immunohistochemistry. We found that RhoGDI
expression is higher in the early stages of breast cancer followed by a
significant decrease in malignant tumors and metastatic lesions (p < 0.01). These
data suggest that downregulation of RhoGDI could be a critical mechanism of
breast tumor development, which may involve the hyperactivation of Rho GTPases
and upregulation of COX-2 activity. Additional studies are warranted to evaluate
the therapeutic potential of inhibiting Rho GTPases and COX-2 for treating breast
cancers.
PMID- 26416249
TI - Direct production of functional matrix metalloproteinase--14 without refolding or
activation and its application for in vitro inhibition assays.
AB - Human matrix metalloproteinase (MMP)-14, a membrane-bound zinc endopeptidase, is
one of the most important cancer targets because it plays central roles in tumor
growth and invasion. Large amounts of active MMP-14 are required for cancer
research and the development of chemical or biological MMP-14 inhibitors. Current
methods of MMP-14 production through refolding and activation are labor
intensive, time-consuming, and often associated with low recovery rates, lot-to
lot variation and heterogeneous products. Here, we report direct production of
the catalytic domain of MMP-14 in the periplasmic space of Escherichia coli. 0.5
mg/L of functional MMP-14 was produced without tedious refolding or problematic
activation process. MMP-14 prepared by simple periplasmic treatment can be
readily utilized to evaluate the potencies of chemical and antibody-based
inhibitors. Furthermore, co-expression of both MMP-14 and antibody Fab fragments
in the periplasm facilitated inhibitory antibody screening by avoiding
purification of MMP-14 or Fabs. We expect this MMP-14 expression strategy can
expedite the development of therapeutic drugs targeting MMPs with biological
significance.
PMID- 26416250
TI - Secondary compounds enhance flammability in a Mediterranean plant.
AB - Some plant secondary compounds, such as terpenes, are very flammable; however,
their role in enhancing plant flammability is poorly understood and often
neglected in reviews on plant chemical ecology. This is relevant as there is
growing evidence that flammability-enhancing traits are adaptive in fire-prone
ecosystems. We analyzed the content of monoterpenes and sesquiterpenes, performed
flammability tests and genotyped microsatellite markers, all in the same
individuals of Rosmarinus officinalis, to evaluate the link between the content
of terpenes, flammability and the genetic similarity among individuals. The
results suggest that terpenes enhance flammability in R. officinalis, and that
variability in flammability among individuals is likely to have a genetic basis.
Overall our results suggest that the capacity to produce and store terpenes can
be considered a flammability-enhancing trait and could have an adaptive value in
fire-prone ecosystems.
PMID- 26416251
TI - Life habits, hox genes, and affinities of a 311 million-year-old holometabolan
larva.
AB - BACKGROUND: Holometabolous insects are the most diverse, speciose and ubiquitous
group of multicellular organisms in terrestrial and freshwater ecosystems. The
enormous evolutionary and ecological success of Holometabola has been attributed
to their unique postembryonic life phases in which nonreproductive and wingless
larvae differ significantly in morphology and life habits from their reproductive
and mostly winged adults, separated by a resting stage, the pupa. Little is known
of the evolutionary developmental mechanisms that produced the holometabolous
larval condition and their Paleozoic origin based on fossils and phylogeny.
RESULTS: We provide a detailed anatomic description of a 311 million-year-old
specimen, the oldest known holometabolous larva, from the Mazon Creek deposits of
Illinois, U.S.A. The head is ovoidal, downwardly oriented, broadly attached to
the anterior thorax, and bears possible simple eyes and antennae with insertions
encircled by molting sutures; other sutures are present but often indistinct.
Mouthparts are generalized, consisting of five recognizable segments: a clypeo
labral complex, mandibles, possible hypopharynx, a maxilla bearing indistinct
palp-like appendages, and labium. Distinctive mandibles are robust, triangular,
and dicondylic. The thorax is delineated into three, nonoverlapping regions of
distinctive surface texture, each with legs of seven elements, the terminal-most
bearing paired claws. The abdomen has ten segments deployed in register with
overlapping tergites; the penultimate segment bears a paired, cercus-like
structure. The anterior eight segments bear clawless leglets more diminutive than
the thoracic legs in length and cross-sectional diameter, and inserted more
ventrolaterally than ventrally on the abdominal sidewall. CONCLUSIONS: Srokalarva
berthei occurred in an evolutionary developmental context likely responsible for
the early macroevolutionary success of holometabolous insects. Srokalarva berthei
bore head and prothoracic structures, leglet series on successive abdominal
segments - in addition to comparable features on a second taxon eight million
years-younger - that indicates Hox-gene regulation of segmental and appendage
patterning among earliest Holometabola. Srokalarva berthei body features suggest
a caterpillar-like body plan and head structures indicating herbivory consistent
with known, contemporaneous insect feeding damage on seed plants. Taxonomic
resolution places Srokalarva berthei as an extinct lineage, apparently possessing
features closer to neuropteroid than other holometabolous lineages.
PMID- 26416252
TI - Haiti and the health marketplace: the role of the private, informal market in
filling the gaps left by the state.
AB - BACKGROUND: In most societies the health marketplace is pluralistic in character,
with a mix of formal and informal providers. In high-income countries, state
regulation of the market helps ensure quality and access and mitigate market
failures. In the present study, using Haiti as a case study, we explore what
happens to the functioning of the pluralistic health marketplace in severely
disrupted environments where the informal sector is able to flourish. METHODS:
The overall research design was qualitative. Research methods included an
extensive documentary and policy analysis, based on peer-reviewed articles, books
and "grey" literature--government policy and program reports, unpublished
research and evaluations, reviews and reviews from key multilateral and bilateral
donors, and non-government organisations, combined with field site visits and in
depth key informant interviews (N = 45). RESULTS: The findings show that state
fragility has resulted in a privatised, commoditised and largely unregulated and
informal health market. While different market segments can be identified, in
reality the boundaries between international/domestic, public/private, for
profit/not-for-profit, legal/illegal are hazy and shifting. DISCUSSION: The lack
of state capacity to provide an enabling environment, establish, and enforce its
regulatory framework has resulted in a highly segmented, heterogeneous and
informal health market. The result is deplorable health indices which are far
below regional averages and many other low-income countries. CONCLUSIONS: Working
in fragile states with limited capacity to undertake the core function of
securing the health of its population requires new and innovative ways of
working. This needs longer time-frames, combining incremental top-down and bottom
up strategies which recognize and work with state and civil society, public and
private actors, formal and informal institutions, and progressively facilitate
changes in the different market functions of supply, demand, regulation and
supporting functions.
PMID- 26416254
TI - Virulence evolution at the front line of spreading epidemics.
AB - Understanding and predicting the spatial spread of emerging pathogens is a major
challenge for the public health management of infectious diseases. Theoretical
epidemiology shows that the speed of an epidemic is governed by the life-history
characteristics of the pathogen and its ability to disperse. Rapid evolution of
these traits during the invasion may thus affect the speed of epidemics. Here we
study the influence of virulence evolution on the spatial spread of an epidemic.
At the edge of the invasion front, we show that more virulent and transmissible
genotypes are expected to win the competition with other pathogens. Behind the
front line, however, more prudent exploitation strategies outcompete virulent
pathogens. Crucially, even when the presence of the virulent mutant is limited to
the edge of the front, the invasion speed can be dramatically altered by pathogen
evolution. We support our analysis with individual-based simulations and we
discuss the additional effects of demographic stochasticity taking place at the
front line on virulence evolution. We confirm that an increase of virulence can
occur at the front, but only if the carrying capacity of the invading pathogen is
large enough. These results are discussed in the light of recent empirical
studies examining virulence evolution at the edge of spreading epidemics.
PMID- 26416253
TI - A cluster randomised feasibility trial evaluating nutritional interventions in
the treatment of malnutrition in care home adult residents.
AB - BACKGROUND: Protein energy malnutrition (PEM) predisposes individuals to disease,
delays recovery from illness and reduces quality of life. Care home residents in
the United Kingdom are especially vulnerable, with an estimated 30 to 42 % at
risk. Evidence for nutritional interventions to address PEM in the care home
setting is lacking. Widely used techniques include food-based intervention and/or
the use of prescribed oral nutritional supplements. To define outcomes and
optimise the design for an adequately powered definitive trial to compare the
efficacy of established nutritional interventions in this setting, a cluster
randomised feasibility trial with a 6-month intervention was undertaken. METHODS:
Care home residents with or at risk of malnutrition were identified across six UK
care home sites from September to December 2013. Homes were cluster randomised to
standard care (SC), food-based intervention (FB) or oral nutritional supplement
intervention (ONS), for 6 months. Key outcomes were trial feasibility and the
acceptability of design, allocated interventions and outcome assessments.
Anthropometry, dietary intake, healthcare resource usage and participant-reported
outcome measures were assessed at baseline and at 3 and 6 months. RESULTS: All
six care homes approached were recruited and retained. Of the 110 residents at
risk of malnutrition, 85 % entered the trial, and 68 % completed the 6-month
intervention. Pre-specified success criteria for feasibility were met for
recruitment and retention, intervention acceptability (resident compliance >=60
%) and measurement of weight, body mass index (BMI), mid-upper arm circumference
and dietary intake (data completeness >80 %). Measurement of handgrip strength
and triceps skinfold thickness was not found to be feasible in this population.
The 95 % confidence interval (CI) data suggested sensitivity to change in dietary
intake for weight, BMI and energy intake between baseline and 3 months when each
intervention (FB and ONS) was compared with SC. CONCLUSIONS: A definitive trial
comparing the efficacy of nutritional support interventions in increasing weight
and BMI in malnourished care home residents can be conducted. However, whilst the
design was feasible, this trial has highlighted the lack of clinically and
patient-relevant outcome measures that are appropriate for use in this setting
for both research and clinical practice. In particular, this trial identified a
need for a more simple measure of functional status, which considers the
limitations of functional tests in the care home population. TRIAL REGISTRATION:
Current Controlled Trials ISRCTN38047922 , Date assigned: 22 April 2014.
PMID- 26416255
TI - Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of
5-Lipoxygenase Inhibitors.
AB - The siderophore myxochelin A is a potent inhibitor of human 5-lipoxygenase (5
LO). To clarify whether the iron-chelating properties of myxochelin A are
responsible for this activity, several analogues of this compound were generated
in the native producer Pyxidicoccus fallax by precursor-directed biosynthesis.
Testing in a cell-free assay unveiled three derivatives with bioactivity
comparable with that of myxochelin A. Furthermore, it became evident that
inhibition of 5-LO by myxochelins does not correlate with their iron affinities.
PMID- 26416256
TI - Developing a carob-based milk beverage using different varieties of carob pods
and two roasting treatments and assessing their effect on quality
characteristics.
AB - BACKGROUND: This work aimed at formulating a carob-based milk beverage and
assessing its chemical and sensory properties. Six varieties of carob pods, each
processed into roasted and unroasted powders, were used to develop 12 prototypes
of the beverage. Chemical and physico-chemical analyses (moisture, ash, fibre,
protein, sugars, total-phenolics, total-antioxidants, water activity and colour)
and sensory tests were conducted. RESULTS: The variety of carob pod had a
significant effect on all chemical variables in carob powders (P < 0.01), except
for sugars, and when incorporated in the beverage, on moisture, total phenolics,
total antioxidant activity and colour parameters (L, a, b; P-values < 0.001).
Roasting treatment significantly increased fibre, total phenolics, total
antioxidant activity (P-values < 0.001), fructose, glucose (P-values < 0.05), and
a-value levels (P < 0.01), significantly lowered moisture (P < 0.05), water
activity, L- and b-values (P-values < 0.001) in carob powders; and significantly
increased the beverage's total phenolics, a-value (P-values < 0.001) and total
antioxidant activity (P < 0.01). Roasting treatment significantly increased the
beverage's acceptability ratings. Beverages formulated with roasted carob powder
had higher ratings for level of residue, colour, caramel odour, mocha odour and
flavour, roasted coffee odour and flavour, viscosity mouthfeel and bitter
aftertaste. Principal component analysis was conducted; PC1 and PC2 separated
attributes according to roasting treatment and variety of carob pods,
respectively. CONCLUSION: The use of Akkari roasted and Baladi Ikleem el Kharoob
roasted to formulate a carob-based milk beverage is recommended. (c) 2015 Society
of Chemical Industry.
PMID- 26416257
TI - Accurate pan-specific prediction of peptide-MHC class II binding affinity with
improved binding core identification.
AB - A key event in the generation of a cellular response against malicious organisms
through the endocytic pathway is binding of peptidic antigens by major
histocompatibility complex class II (MHC class II) molecules. The bound peptide
is then presented on the cell surface where it can be recognized by T helper
lymphocytes. NetMHCIIpan is a state-of-the-art method for the quantitative
prediction of peptide binding to any human or mouse MHC class II molecule of
known sequence. In this paper, we describe an updated version of the method with
improved peptide binding register identification. Binding register prediction is
concerned with determining the minimal core region of nine residues directly in
contact with the MHC binding cleft, a crucial piece of information both for the
identification and design of CD4(+) T cell antigens. When applied to a set of 51
crystal structures of peptide-MHC complexes with known binding registers, the new
method NetMHCIIpan-3.1 significantly outperformed the earlier 3.0 version. We
illustrate the impact of accurate binding core identification for the
interpretation of T cell cross-reactivity using tetramer double staining with a
CMV epitope and its variants mapped to the epitope binding core. NetMHCIIpan is
publicly available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.1 .
PMID- 26416258
TI - Fournier's gangrene at a tertiary health facility in northwestern Tanzania: a
single centre experiences with 84 patients.
AB - BACKGROUND: Fournier's gangrene (FG) is a rare, rapidly progressive, necrotizing
fasciitis of the external genitalia and perineum, leading to soft-tissue
necrosis. Despite antibiotics and aggressive debridement, the mortality rate of
FG remains high. This study describes our experiences in the management of FG and
identifies prognostic factors. METHODS: This was a descriptive retrospective
study of patients with FG treated at Bugando Medical Centre between November 2006
and April 2014. RESULTS: A total of 84 patients (M:F = 41:1) were studied. The
median age was 34 years (range 15-76 years). The most common predisposing factor
was diabetes mellitus (16.7%). Nine (11.3%) patients were HIV positive. Bacterial
culture results were obtained in only 46 (54.8%) patients. Of these, 38(82.6%)
had polymicrobial bacterial growth while 8 (17.4%) had monomicrobial bacterial
growth. Escherichia coli (28.3%) were the most frequent bacterial organism
isolated. All the microorganisms isolated showed high resistance to commonly used
antibiotics except for Meropenem and imipenem, which were 100% sensitive each
respectively. All patients were treated with a common approach of resuscitation,
broad-spectrum antibiotics, and wide surgical excision. The median length of
hospital stay (LOS) was 28 days and mortality rate was 28.6%. Systemic
inflammatory response syndrome and diabetes mellitus were significantly
associated with prolonged LOS (p < 0.001), whereas advancing age (>60 years),
late presentation (>48 h), systemic inflammatory response syndrome on admission,
diabetes mellitus, extension of infection to the abdominal wall, FG severity
score >9 and HIV infection with CD4 count <200 MUl/cells) were independent
predictors of mortality (p < 0.001). CONCLUSION: Fournier's gangrene remains a
very severe disease with high mortality rates. Early recognition of infection
associated with invasive and aggressive treatment is essential for attempting to
reduce mortality rates associated with this disease in our setting.
PMID- 26416259
TI - [Preliminary results for ambulatory surgery for vaginal prolapse].
AB - OBJECTIVE, PATIENTS AND METHODS: From a study of 65 patients with vaginal
prolapse, we studied 56 patients treated by the Elevate technic during an
ambulatory hospitalisation. RESULTS: Seven patients failed to the ambulatory
protocol and needed to stay. Three of them for urinary retention. Eighty-eight
percent of the patients were satisfied by this protocol. CONCLUSION: This study
shows the feasibility of prolapse surgery in an ambulatory settings.
PMID- 26416260
TI - Microfluidic Integration of a Cloth-Based Hybridization Array System (CHAS) for
Rapid, Colorimetric Detection of Enterohemorrhagic Escherichia coli (EHEC) Using
an Articulated, Centrifugal Platform.
AB - We describe the translation of a cloth-based hybridization array system (CHAS), a
colorimetric DNA detection method that is used by food inspection laboratories
for colony screening of pathogenic agents, onto a microfluidic chip format. We
also introduce an articulated centrifugal platform with a novel fluid
manipulation concept based on changes in the orientation of the chip with respect
to the centrifugal force field to time the passage of multiple components
required for the process. The platform features two movable and motorized
carriers that can be reoriented on demand between 0 and 360 degrees during stage
rotation. Articulation of the chip can be used to trigger on-the-fly fluid
dispensing through independently addressable siphon structures or to relocate
solutions against the centrifugal force field, making them newly accessible for
downstream transfer. With the microfluidic CHAS, we achieved significant
reduction in the size of the cloth substrate as well as the volume of reagents
and wash solutions. Both the chip design and the operational protocol were
optimized to perform the entire process in a reliable, fully automated fashion. A
demonstration with PCR-amplified genomic DNA confirms on-chip detection and
identification of Escherichia coli O157:H7 from colony isolates in a colorimetric
multiplex assay using rfbO157, fliCH7, vt1, and vt2 genes.
PMID- 26416261
TI - Altered terminal Schwann cell morphology precedes denervation in SOD1 mice.
AB - In mice that express SOD1 mutations found in human motor neuron disease,
degeneration begins in the periphery for reasons that remain unknown. At the
neuromuscular junction (NMJ), terminal Schwann cells (TSCs) have an intimate
relationship with motor terminals and are believed to help maintain the integrity
of the motor terminal. Recent evidence indicates that TSCs in some SOD1 mice
exhibit abnormal functional properties, but other aspects of possible TSC
involvement remain unknown. In this study, an analysis of TSC morphology and
number was performed in relation to NMJ innervation status in mice which express
the G93A SOD1 mutation. At P30, all NMJs of the fast medial gastrocnemius (MG)
muscle were fully innervated by a single motor axon but 50% of NMJs lacked TSC
cell bodies and were instead covered by the processes of Schwann cells with cell
bodies located on the preterminal axons. NMJs in P30 slow soleus muscles were
also fully innervated by single motor axons and only 5% of NMJs lacked a TSC cell
body. At P60, about 25% of MG NMJs were denervated and lacked labeling for TSCs
while about 60% of innervated NMJs lacked TSC cell bodies. In contrast, 96% of
P60 soleus NMJs were innervated while 9% of innervated NMJs lacked TSC cell
bodies. The pattern of TSC abnormalities found at P30 thus correlates with the
pattern of denervation found at P60. Evidence from mice that express the G85R
SOD1 mutation indicate that TSC abnormalities are not unique for mice that
express G93A SOD1 mutations. These results add to an emerging understanding that
TSCs may play a role in motor terminal degeneration and denervation in animal
models of motor neuron disease.
PMID- 26416262
TI - Exercise pathophysiology and the role of oxygen therapy in idiopathic
interstitial pneumonia.
AB - Exercise limitation is a common feature in idiopathic interstitial pneumonia
(IIP). There are multiple contributing pathophysiological mechanisms, including
ventilatory mechanical limitation, impaired gas exchange, pulmonary vascular
insufficiency and peripheral muscle dysfunction. Progressive exertional dyspnoea
and functional incapacity impact significantly on quality of life. Exercise
induced desaturation is frequently observed and is predictive of poorer outcomes.
Tests to assess the cardiorespiratory system under stress (e.g. cardiopulmonary
exercise testing and the 6-min walk test) can provide important physiologic and
prognostic information as adjuncts to resting measurements of lung function.
Despite many advances in understanding disease mechanisms, therapies to improve
exercise capacity, symptom burden and quality of life are lacking. Exercise
training and supplemental oxygen are two potential interventions that require
closer evaluation in patients with IIP.
PMID- 26416263
TI - Supplementation of metabolizable protein during late gestation and fetal number
impact ewe organ mass, maternal serum hormone and metabolite concentrations, and
conceptus measurements.
AB - To examine the effects of maternal metabolizable protein (MP) supplementation
during late gestation on serum hormone and metabolites and organ masses,
multiparous ewes (n = 45) carrying singletons or twins were allotted randomly
(within pregnancy group) to 1 of 3 treatments: 60% (MP60), 80% (MP80), or 100%
(MP100) of MP requirements. Blood samples were drawn before the initiation of
diets (day 100) and before slaughter (day 130) for chemistry panel analysis and
weekly for hormone analysis including progesterone (P4) and estradiol-17beta
(E2). At day 130, ewe organ masses were recorded. Despite being fed isocaloric
diets, MP60 ewes gained less weight throughout pregnancy compared with MP80 and
MP100 ewes which were similar. Although diet did not impact E2 or P4
concentrations, ewes carrying twins had greater (P < 0.05) concentrations of both
as gestation advanced. Albumin, aspartate aminotransferase, and total protein
were reduced (P < 0.05) in MP60 compared with MP100 ewes near term. There was a
diet by fetal number interaction (P = 0.03) for lactate dehydrogenase. Twin
carrying MP80 ewes had greater lactate dehydrogenase compared with all other
groups on day 130 of gestation. Ewes that were fed MP80 had greater body weight
on day 130 of gestation compared with MP60 ewes. Kidney and heart weights were
lighter in MP60 ewes compared with MP80 ewes. There was a maternal diet by fetal
number interaction (P = 0.05) on fetal weight per unit empty ewe body weight. In
ewes carrying singletons, MP60 ewes supported less fetal weight compared with
MP100. In contrast, MP60 ewes supported more fetal mass compared with MP100 ewes
when carrying twins. The level of protein, and not just total energy, in the diet
appears to impact some aspects of the maternal system. Moreover, it appears some
measurements of mobilizing maternal body resources are enhanced in ewes carrying
twins.
PMID- 26416264
TI - PDZD7 and hearing loss: More than just a modifier.
AB - Deafness is the most frequent sensory disorder. With over 90 genes and 110 loci
causally implicated in non-syndromic hearing loss, it is phenotypically and
genetically heterogeneous. Here, we investigate the genetic etiology of deafness
in four families of Iranian origin segregating autosomal recessive non-syndromic
hearing loss (ARNSHL). We used a combination of linkage analysis, homozygosity
mapping, and a targeted genomic enrichment platform to simultaneously screen 90
known deafness-causing genes for pathogenic variants. Variant segregation was
confirmed by Sanger sequencing. Linkage analysis and homozygosity mapping showed
segregation with the DFNB57 locus on chromosome 10 in two families. Targeted
genomic enrichment with massively parallel sequencing identified causal variants
in PDZD7: a homozygous missense variant (p.Gly103Arg) in one family and compound
heterozygosity for missense (p.Met285Arg) and nonsense (p.Tyr500Ter) variants in
the second family. Screening of two additional families identified two more
variants: (p.Gly228Arg) and (p.Gln526Ter). Variant segregation with the hearing
loss phenotype was confirmed in all families by Sanger sequencing. The missense
variants are predicted to be deleterious, and the two nonsense mutations produce
null alleles. This report is the first to show that mutations in PDZD7 cause
ARNSHL, a finding that offers addition insight into the USH2 interactome. We also
describe a novel likely disease-causing mutation in CIB2 and illustrate the
complexity associated with gene identification in diseases that exhibit large
genetic and phenotypic heterogeneity.
PMID- 26416265
TI - Pain pressure threshold of a muscle tender spot increases following local and non
local rolling massage.
AB - BACKGROUND: The aim of the present study was to determine the acute effect of
rolling massage on pressure pain threshold (PPT) in individuals with tender spots
in their plantar flexor muscles. METHODS: In a randomized control trial and
single blinded study, tender spots were identified in 150 participants' plantar
flexor muscles (gastrocnemius or soleus). Then participants were randomly
assigned to one of five intervention groups (n = 30): 1) heavy rolling massage on
the calf that exhibited the higher tenderness (Ipsi-R), 2) heavy rolling massage
on the contralateral calf (Contra-R), 3) light stroking of the skin with roller
massager on the calf that exhibited the higher tenderness (Sham), 4) manual
massage on the calf that exhibited the higher tenderness (Ipsi-M) and 5) no
intervention (Control). PPT was measured at 30 s and up to 15 min post
intervention via a pressure algometer. RESULTS: At 30 s post-intervention, the
Ipsi-R (24 %) and Contra-R (21 %) demonstrated higher (p < 0.03) PPT values
compared with Control and Sham. During 15 min post-intervention, PPT was higher
(p < 0.05) following Ipsi-R (19.2 %), Contra-R (15.9 %) and Ipsi-M (10.9 %)
compared with Control. There was no difference between the effects of three deep
tissue massages (Ipsi-R, Ipsi-M and Contra-R) on PPT. DISCUSSION: Whereas the
increased PPT following ipsilateral massage (Ipsi-R and Ipsi-M) might be
attributed to the release of fibrous adhesions; the non-localized effect of
rolling massage on the contralateral limb suggests that other mechanisms such as
a central pain-modulatory system play a role in mediation of perceived pain
following brief tissue massage. CONCLUSION: Overall, rolling massage over a
tender spot reduces pain perception. TRIAL REGISTRATION: ClinicalTrials.gov (
NCT02528812 ), August 19(th), 2015.
PMID- 26416266
TI - Extrinsic thoracic spinal cord compression related to supine position: from
diagnosis to the creation of a spinal protection shield.
AB - BACKGROUND: Rapidly progressing extrinsic spinal cord compression syndromes are
rare, especially when the compression is associated with the supine position.
PURPOSE: This work presents a case of extrinsic thoracic spinal cord compression
related to the supine position and describes our approach from diagnosis to the
technical therapeutic creation of a spinal protection shield. STUDY DESIGN: One
case of a patient suffering from extrinsic spinal cord compression syndrome is
reported. PATIENT SAMPLE: We report the case of a Coptic priest patient who, as a
result of Pott disease sequelae, underwent several decompressive and stabilizing
surgeries for major kyphoscoliosis. Consequently, he developed extrinsic thoracic
spinal cord compression caused by the supine position. OUTCOME MEASURES: After
each instrumentation device removal, we noticed progressive severe paraparesis
when the patient was supine. Imaging assessment confirmed spinal dynamic and
intermittent compressions triggered by the supine position, which was facilitated
by the exposure and vulnerability of the thoracic spine cord. METHODS: We
implanted a tailored titanium mesh spinal protection shield and a trapezius flap
for spine coverage. This work presents the diagnostic aspects as well as several
surgical technique options. RESULTS: At the 6-year follow-up, the patient's
neurologic conditions were significantly improved. We report neurologic
improvements, no sphincter disorder, persistent spasticity, and lower limbs
weakness not affecting full ambulation. CONCLUSIONS: To our knowledge, no other
case of spinal protection shield in compressions caused by the supine position
have been studied. The surgical and technical management therefore remains
innovative.
PMID- 26416267
TI - Qualitative Effects of Monovalent Vaccination Against Rotavirus: A Comparison of
North America and South America.
AB - Rotavirus is the most common cause of severe gastroenteritis in young children
worldwide. The introduction of vaccination programs has led to a significant
reduction in number of hospitalizations due to rotavirus in North and South
American countries. Little work has been done, however, to examine the
differential impact of vaccination as a function of strain distribution and
strain-specific vaccine efficacy. We developed a two-strain epidemiological model
of rotavirus transmission, and used it to examine the effects of a monovalent
vaccine (Rotarix) on the qualitative behaviors of infection levels in a
population. For contrast, we parameterized our model with strain distribution
data from North America and from South America. In all cases, the introduction of
the vaccine led to significant decreases in the prevalence of primary infection
due to both strains for a decade or more, after which the overall prevalence
recovers to near pre-vaccination levels. The prevalence of G1P[8] is
significantly higher in North America (73 % of all rotavirus infections) compared
to that in South America (34 %). Our model predicts that the introduction of
Rotarix might result in major strain replacement in regions such as North America
where the prevalence of G1P[8] is relatively high, due to higher efficacy of
Rotarix against infection caused by G1P[8], while regions with lower prevalence
of G1P[8], such as South America, are not susceptible to major strain
replacement.
PMID- 26416269
TI - FTY720 Abrogates Collagen-Induced Arthritis by Hindering Dendritic Cell Migration
to Local Lymph Nodes.
AB - Because dendritic cells (DCs) play critical roles in the pathogenesis of
rheumatoid arthritis, modulation of their functions could serve as a novel
therapy. In this study, we demonstrated that FTY720 treatment significantly
suppressed the incidence and severity of collagen-induced arthritis (CIA) in
DBA/1J mice via the modulation of DC functions. In FTY720-treated CIA mice, a
decrease in the number of DCs in local draining lymph nodes (LNs) was observed.
In vitro, FTY720 inhibited the trafficking of LPS-stimulated bone marrow-derived
DCs (BMDCs). Decreased secretion of CCL19 and downregulation of CCR7 on DCs may
explain the mechanisms underlying the impairment of DC migration induced by
FTY720. In a DC-induced mouse arthritis model, FTY720 treatment also suppressed
the incidence and severity of arthritis, which was correlated with a decrease in
the migration of injected BMDCs to draining LNs. Although lower levels of
costimulatory molecules (CD40, CD80, and CD86) and I-A(q) expressed on LN DCs
were observed in FTY720-treated mice, in vitro analysis showed no effect of
FTY720 on LPS-stimulated BMDC maturation. Furthermore, LN cells from FTY720
treated CIA mice displayed diminished production of proinflammatory cytokines in
response to collagen II and Con A stimulation. In addition, the ratio of Th1/Th2
in the draining LNs of mice with DC-induced arthritis was decreased upon FTY720
treatment. This finding was consistent with the fact that FTY720 suppressed IL
12p70 production in cultured BMDCs. Taken together, these results indicate that
inhibition of DC migration by FTY720 may provide a novel approach in treating
autoimmune diseases such as rheumatoid arthritis.
PMID- 26416268
TI - A Gene Expression Signature That Correlates with CD8+ T Cell Expansion in Acute
EBV Infection.
AB - Virus-specific CD8(+) T cells expand dramatically during acute EBV infection, and
their persistence is important for lifelong control of EBV-related disease. To
better define the generation and maintenance of these effective CD8(+) T cell
responses, we used microarrays to characterize gene expression in total and EBV
specific CD8(+) T cells isolated from the peripheral blood of 10 individuals
followed from acute infectious mononucleosis (AIM) into convalescence (CONV). In
total CD8(+) T cells, differential expression of genes in AIM and CONV was most
pronounced among those encoding proteins important in T cell
activation/differentiation, cell division/metabolism, chemokines/cytokines and
receptors, signaling and transcription factors (TF), immune effector functions,
and negative regulators. Within these categories, we identified 28 genes that
correlated with CD8(+) T cell expansion in response to an acute EBV infection. In
EBV-specific CD8(+) T cells, we identified 33 genes that were differentially
expressed in AIM and CONV. Two important TF, T-bet and eomesodermin, were
upregulated and maintained at similar levels in both AIM and CONV; in contrast,
protein expression declined from AIM to CONV. Expression of these TF varied among
cells with different epitope specificities. Collectively, gene and protein
expression patterns suggest that a large proportion, if not a majority of CD8(+)
T cells in AIM are virus specific, activated, dividing, and primed to exert
effector activities. High expression of T-bet and eomesodermin may help to
maintain effector mechanisms in activated cells and to enable proliferation and
transition to earlier differentiation states in CONV.
PMID- 26416270
TI - Cutting Edge: CTLA-4Ig Inhibits Memory B Cell Responses and Promotes Allograft
Survival in Sensitized Recipients.
AB - Sensitized recipients with pretransplant donor-specific Abs are at higher risk
for Ab-mediated rejection than nonsensitized recipients, yet little is known
about the properties of memory B cells that are central to the recall
alloantibody responses. Using cell enrichment and MHC class I tetramers, C57BL/6
mice sensitized with BALB/c splenocytes were shown to harbor H-2K(d)-specific
IgG(+) memory B cells with a post-germinal center phenotype
(CD73(+)CD273(+)CD38(hi)CD138(-)GL7(-)). These memory B cells adoptively
transferred into naive mice without memory T cells recapitulated class-switched
recall alloantibody responses. During recall, memory H-2K(d)-specific B cells
preferentially differentiated into Ab-secreting cells, whereas in the primary
response, H-2K(d)-specific B cells differentiated into germinal center cells.
Finally, our studies revealed that, despite fundamental differences in
alloreactive B cell fates in sensitized versus naive recipients, CTLA-4Ig was
unexpectedly effective at constraining B cell responses and heart allograft
rejection in sensitized recipients.
PMID- 26416272
TI - Mechanistic Basis for Epitope Proofreading in the Peptide-Loading Complex.
AB - The peptide-loading complex plays a pivotal role in Ag processing and is thus
central to the efficient immune recognition of virally and malignantly
transformed cells. The underlying mechanism by which MHC class I (MHC I)
molecules sample immunodominant peptide epitopes, however, remains poorly
understood. In this article, we delineate the interaction between tapasin (Tsn)
and MHC I molecules. We followed the process of peptide editing in real time
after ultra-fast photoconversion to pseudoempty MHC I molecules. Tsn
discriminates between MHC I loaded with optimal and MHC I bound to suboptimal
cargo. This differential interaction is key to understanding the kinetics of
epitope proofreading. To elucidate the underlying mechanism at the atomic level,
we modeled the Tsn/MHC I complex using all-atom molecular dynamics simulations.
We present a catalytic working cycle, in which Tsn binds to MHC I with suboptimal
cargo and thereby adjusts the energy landscape in favor of MHC I complexes with
immunodominant epitopes.
PMID- 26416271
TI - Continuous Antigenic Stimulation of DO11.10 TCR Transgenic Mice in the Presence
or Absence of IL-1beta: Possible Implications for Mechanisms of T Cell Depletion
in HIV Disease.
AB - Untreated HIV disease is associated with chronic immune activation and CD4(+) T
cell depletion. A variety of mechanisms have been invoked to account for CD4(+) T
cell depletion in this setting, but the quantitative contributions of these
proposed mechanisms over time remain unclear. We turned to the DO11.10 TCR
transgenic mouse model, where OVA is recognized in the context of H-2(d), to
explore the impact of chronic antigenic stimulation on CD4(+) T cell dynamics. To
model dichotomous states of persistent Ag exposure in the presence or absence of
proinflammatory stimulation, we administered OVA peptide to these mice on a
continuous basis with or without the prototypic proinflammatory cytokine, IL
1beta. In both cases, circulating Ag-specific CD4(+) T cells were depleted.
However, in the absence of IL-1beta, there was limited proliferation and
effector/memory conversion of Ag-specific T cells, depletion of peripheral CD4(+)
T cells in hematolymphoid organs, and systemic induction of regulatory
Foxp3(+)CD4(+) T cells, as often observed in late-stage HIV disease. By contrast,
when OVA peptide was administered in the presence of IL-1beta, effector/memory
phenotype T cells expanded and the typical symptoms of heightened immune
activation were observed. Acknowledging the imperfect and incomplete relationship
between Ag-stimulated DO11.10 TCR transgenic mice and HIV-infected humans, our
data suggest that CD4(+) T cell depletion in the setting of HIV disease may
reflect, at least in part, chronic Ag exposure in the absence of proinflammatory
signals and/or appropriate APC functions.
PMID- 26416273
TI - Species-Specific Minimal Sequence Motif for Oligodeoxyribonucleotides Activating
Mouse TLR9.
AB - Synthetic oligodeoxyribonucleotides (ODNs) containing unmethylated CpG
recapitulate the activation of TLR9 by microbial DNA. ODNs are potent stimulators
of the immune response in cells expressing TLR9. Despite extensive use of mice as
experimental animals in basic and applied immunological research, the key
sequence determinants that govern the activation of mouse TLR9 by ODNs have not
been well defined. We performed a systematic investigation of the sequence motif
of B class phosphodiester ODNs to identify the sequence properties that govern
mouse TLR9 activation. In contrast to ODNs activating human TLR9, where the
minimal sequence motif for the receptor activation comprises a pair of closely
positioned CpGs we found that the mouse TLR9 requires a single CpG positioned 4-6
nt from the 5'-end. Activation is augmented by a 5'TCC sequence one to three
nucleotides from the CG. The distance of the CG dinucleotide of four to six
nucleotides from the 5'-end and the ODN's length fine-tunes activation of mouse
macrophages. Length of the ODN <23 and >29 nt decreases activation of dendritic
cells. The ODNs with minimal sequence induce Th1-type cytokine synthesis in
dendritic cells and confirm the expression of cell surface markers in B cells.
Identification of the minimal sequence provides an insight into the sequence
selectivity of mouse TLR9 and points to the differences in the receptor
selectivity between species probably as a result of differences in the receptor
binding sites.
PMID- 26416274
TI - Polarization of Monocytic Myeloid-Derived Suppressor Cells by Hepatitis B Surface
Antigen Is Mediated via ERK/IL-6/STAT3 Signaling Feedback and Restrains the
Activation of T Cells in Chronic Hepatitis B Virus Infection.
AB - Chronic hepatitis B virus (HBV) infection is characterized by T cell tolerance to
virus. Although inhibition of T cell responses by myeloid-derived suppressor
cells (MDSCs) has been observed in patients with chronic hepatitis B (CHB), the
mechanism for expansion of MDSCs remains ambiguous. In this study, a significant
increased frequency of monocytic MDSCs (mMDSCs) was shown positively correlated
to level of HBsAg in the patients with CHB. We further found hepatitis B surface
Ag (HBsAg) efficiently promoted differentiation of mMDSCs in vitro, and monocytes
in PBMCs performed as the progenitors. This required the activation of ERK/IL
6/STAT3 signaling feedback. Importantly, the mMDSCs polarized by HBsAg in vitro
acquired the ability to suppress T cell activation. Additionally, treatment of
all-trans retinoic acid, an MDSC-targeted drug, restored the proliferation and
IFN-gamma production by HBV-specific CD4(+) and CD8(+) T cells in PBMCs from
patients with CHB and prevented increase of viral load in mouse model. In
summary, HBsAg maintains HBV persistence and suppresses T cell responses by
promoting differentiation of monocytes into mMDSCs. A therapy aimed at the
abrogation of MDSCs may help to disrupt immune suppression in patients with CHB.
PMID- 26416277
TI - MHC/Peptide-Specific Interaction of the Humoral Immune System: A New Category of
Antibodies.
AB - Abs bind to unprocessed Ags, whereas cytotoxic CD8(+) T cells recognize peptides
derived from endogenously processed Ags presented in the context of class I MHC
complexes. We screened, by ELISA, human sera for Abs reacting specifically with
the influenza matrix protein (IMP)-derived peptide(58-66) displayed by HLA-A*0201
complexes. Among 653 healthy volunteers, blood donors, and women on delivery,
high-titered HLA-A*0201/IMP(58-66) complex-specific IgG Abs were detected in 11
females with a history of pregnancies and in 1 male, all HLA-A*0201(-). These Abs
had the same specificity as HLA-A*0201/IMP(58-66)-specific cytotoxic T cells and
bound neither to HLA-A*0201 nor the peptide alone. No such Abs were detected in
HLA-A*0201(+) volunteers. These Abs were not cross-reactive to other self-MHC
class I alleles displaying IMP(58-66), but bound to MHC class I complexes of an
HLA nonidentical offspring. HLA-A*0201/IMP(58-66) Abs were also detected in the
cord blood of newborns, indicating that HLA-A*0201/IMP(58-66) Abs are produced in
HLA-A*0201(-) mothers and enter the fetal blood system. That Abs can bind to
peptides derived from endogenous Ags presented by MHC complexes opens new
perspectives on interactions between the cellular and humoral immune system.
PMID- 26416275
TI - Regulation of Adaptive NK Cells and CD8 T Cells by HLA-C Correlates with
Allogeneic Hematopoietic Cell Transplantation and with Cytomegalovirus
Reactivation.
AB - Mass cytometry was used to investigate the effect of CMV reactivation on
lymphocyte reconstitution in hematopoietic cell transplant patients. For eight
transplant recipients (four CMV negative and four CMV positive), we studied PBMCs
obtained 6 mo after unrelated donor hematopoietic cell transplantation (HCT).
Forty cell-surface markers, distinguishing all major leukocyte populations in
PBMC, were analyzed with mass cytometry. This group included 34 NK cell markers.
Compared with healthy controls, transplant recipients had higher HLA-C expression
on CD56(-)CD16(+) NK cells, B cells, CD33(bright) myeloid cells, and CD4CD8 T
cells. The increase in HLA-C expression was greater for CMV-positive HCT
recipients than for CMV negative recipients. Present in CMV-positive HCT
recipients, but not in CMV-negative HCT recipients or controls, is a population
of killer cell Ig-like receptor (KIR)-expressing CD8 T cells not previously
described. These CD8 T cells coexpress CD56, CD57, and NKG2C. The HCT recipients
also have a population of CD57(+)NKG2A(+) NK cells that preferentially express
KIR2DL1. An inverse correlation was observed between the frequencies of
CD57(+)NKG2C(+) NK cells and CD57(+)NKG2A(+) NK cells. Although CD57(+)NKG2A(+)
NK cells are less abundant in CMV-positive recipients, their phenotype is of a
more activated cell than the CD57(+)NKG2A(+) NK cells of controls and CMV
negative HCT recipients. These data demonstrate that HCT and CMV reactivation are
associated with an increased expression of HLA-C. This could influence NK cell
education during lymphocyte reconstitution. The increased inhibitory KIR
expression by proliferating CMV-specific CD8 T cells suggests regulatory
interactions between HLA-C and KIR might promote Graft-versus-Leukemia effects
following transplantation.
PMID- 26416276
TI - SHIP-1 Couples to the Dectin-1 hemITAM and Selectively Modulates Reactive Oxygen
Species Production in Dendritic Cells in Response to Candida albicans.
AB - Dectin-1 (Clec7a) is a paradigmatic C-type lectin receptor that binds Syk through
a hemITAM motif and couples sensing of pathogens such as fungi to induction of
innate responses. Dectin-1 engagement triggers a plethora of activating events,
but little is known about the modulation of such pathways. Trying to define a
more precise picture of early Dectin-1 signaling, we explored the interactome of
the intracellular tail of the receptor in mouse dendritic cells. We found
unexpected binding of SHIP-1 phosphatase to the phosphorylated hemITAM. SHIP-1
colocalized with Dectin-1 during phagocytosis of zymosan in a hemITAM-dependent
fashion. Moreover, endogenous SHIP-1 relocated to live or heat-killed Candida
albicans-containing phagosomes in a Dectin-1-dependent manner in GM-CSF-derived
bone marrow cells (GM-BM). However, SHIP-1 absence in GM-BM did not affect
activation of MAPK or production of cytokines and readouts dependent on NF-kappaB
and NFAT. Notably, ROS production was enhanced in SHIP-1-deficient GM-BM treated
with heat-killed C. albicans, live C. albicans, or the specific Dectin-1 agonists
curdlan or whole glucan particles. This increased oxidative burst was dependent
on Dectin-1, Syk, PI3K, phosphoinositide-dependent protein kinase 1, and NADPH
oxidase. GM-BM from CD11c?SHIP-1 mice also showed increased killing activity
against live C. albicans that was dependent on Dectin-1, Syk, and NADPH oxidase.
These results illustrate the complexity of myeloid C-type lectin receptor
signaling, and how an activating hemITAM can also couple to intracellular
inositol phosphatases to modulate selected functional responses and tightly
regulate processes such as ROS production that could be deleterious to the host.
PMID- 26416278
TI - Human beta Defensin-3 Increases CD86 Expression on Monocytes by Activating the
ATP-Gated Channel P2X7.
AB - Human beta defensin-3 (hBD-3), an epithelial cell-derived antimicrobial peptide,
mediates chemotaxis and activation of myeloid cells. In this study, we provide
evidence that hBD-3 induces the costimulatory molecule CD86 on primary human
monocytes by a mechanism involving autocrine activation of ionotropic P2X7
receptors (P2X7R) by ATP. Incubation of monocytes with hBD-3 resulted in
increased expression of both the CD80 and CD86 costimulatory molecules. Treatment
of monocytes with a selective P2X7R antagonist inhibited the ability of hBD-3 to
induce expression of CD86 but not CD80. The hBD-3-dependent upregulation of CD86
was also attenuated in monocytes incubated with apyrase, a potent scavenger of
extracellular ATP. Finally, direct activation of monocyte P2X7R by exogenous ATP
mimicked the ability of hBD-3 to induce CD86 expression. These data suggest that
hBD-3 induces monocyte activation by both P2X7-dependent (CD86 upregulation) and
P2X7-independent (CD80 upregulation) signaling mechanisms and raise the
possibility that activation of P2X7R could play an important role in shaping the
inflammatory microenvironment in conditions where hBD-3 is highly expressed, such
as psoriasis or oral carcinoma.
PMID- 26416279
TI - Fibrocytes Differ from Macrophages but Can Be Infected with HIV-1.
AB - Fibrocytes (fibroblastic leukocytes) are recently identified as unique
hematopoietic cells with features of both macrophages and fibroblasts. Fibrocytes
are known to contribute to the remodeling or fibrosis of various injured tissues.
However, their role in viral infection is not fully understood. In this study, we
show that differentiated fibrocytes are phenotypically distinguishable from
macrophages but can be infected with HIV-1. Importantly, fibrocytes exhibited
persistently infected cell-like phenotypes, the degree of which was more apparent
than macrophages. The infected fibrocytes produced replication-competent HIV-1,
but expressed HIV-1 mRNA at low levels and strongly resisted HIV-1-induced cell
death, which enabled them to support an extremely long-term HIV-1 production at
low but steady levels. More importantly, our results suggested that fibrocytes
were susceptible to HIV-1 regardless of their differentiation state, in contrast
to the fact that monocytes become susceptible to HIV-1 after the differentiation
into macrophages. Our findings indicate that fibrocytes are the previously
unreported HIV-1 host cells, and they suggest the importance of considering
fibrocytes as one of the long-lived persistently infected cells for curing HIV-1.
PMID- 26416280
TI - ATF3 Is a Key Regulator of Macrophage IFN Responses.
AB - Cytokines and IFNs downstream of innate immune pathways are critical for mounting
an appropriate immune response to microbial infection. However, the expression of
these inflammatory mediators is tightly regulated, as uncontrolled production can
result in tissue damage and lead to chronic inflammatory conditions and
autoimmune diseases. Activating transcription factor 3 (ATF3) is an important
transcriptional modulator that limits the inflammatory response by controlling
the expression of a number of cytokines and chemokines. However, its role in
modulating IFN responses remains poorly defined. In this study, we demonstrate
that ATF3 expression in macrophages is necessary for governing basal IFN-beta
expression, as well as the magnitude of IFN-beta cytokine production following
activation of innate immune receptors. We found that ATF3 acted as a
transcriptional repressor and regulated IFN-beta via direct binding to a
previously unidentified specific regulatory site distal to the Ifnb1 promoter.
Additionally, we observed that ATF3 itself is a type I IFN-inducible gene, and
that ATF3 further modulates the expression of a subset of inflammatory genes
downstream of IFN signaling, suggesting it constitutes a key component of an IFN
negative feedback loop. Consistent with this, macrophages deficient in Atf3
showed enhanced viral clearance in lymphocytic choriomeningitis virus and
vesicular stomatitis virus infection models. Our study therefore demonstrates an
important role for ATF3 in modulating IFN responses in macrophages by controlling
basal and inducible levels of IFNbeta, as well as the expression of genes
downstream of IFN signaling.
PMID- 26416282
TI - Engagement of the Aryl Hydrocarbon Receptor in Mycobacterium tuberculosis
Infected Macrophages Has Pleiotropic Effects on Innate Immune Signaling.
AB - Understanding the mechanisms of host macrophage responses to Mycobacterium
tuberculosis is essential for uncovering potential avenues of intervention to
boost host resistance to infection. Macrophage transcriptome profiling revealed
that M. tuberculosis infection strongly induced the expression of several enzymes
controlling tryptophan catabolism. These included IDO1 and tryptophan 2,3
dioxygenase, which catalyze the rate-limiting step in the kynurenine pathway,
producing ligands for the aryl hydrocarbon receptor (AHR). The AHR and
heterodimeric partners AHR nuclear translocator and RELB are robustly expressed,
and AHR and RELB levels increased further during infection. Infection enhanced
AHR/AHR nuclear translocator and AHR/RELB DNA binding and stimulated the
expression of AHR target genes, including that encoding the inflammatory cytokine
IL-1beta. AHR target gene expression was further enhanced by exogenous
kynurenine, and exogenous tryptophan, kynurenine, or synthetic agonist indirubin
reduced mycobacterial viability. Comparative expression profiling revealed that
AHR ablation diminished the expression of numerous genes implicated in innate
immune responses, including several cytokines. Notably, AHR depletion reduced the
expression of IL23A and IL12B transcripts, which encode subunits of IL-23, a
macrophage cytokine that stimulates production of IL-22 by innate lymphoid cells.
AHR directly induced IL23A transcription in human and mouse macrophages through
near-upstream enhancer regions. Taken together, these findings show that AHR
signaling is strongly engaged in M. tuberculosis-infected macrophages and has
widespread effects on innate immune responses. Moreover, they reveal a cascade of
AHR-driven innate immune signaling, because IL-1beta and IL-23 stimulate T cell
subsets producing IL-22, another direct target of AHR transactivation.
PMID- 26416281
TI - Effect of IL-7 Therapy on Naive and Memory T Cell Homeostasis in Aged Rhesus
Macaques.
AB - Aging is associated with gradual deterioration of adaptive immune function, a
hallmark of which is the profound loss of naive T cells (TN) associated with
decline in thymic output and export of new cells into the peripheral T cell pool.
Because the lymphotropic cytokine IL-7 plays crucial roles in both development of
TN in the thymus and TN homeostasis in the periphery, we sought to determine the
extent to which therapeutic administration of IL-7 could reverse TN deficiency in
aging rhesus macaques (RM), either by enhancement of the demonstrably reduced
thymopoiesis or by peripheral TN expansion. Our results indicate that treatment
of both adult (8-15 y) and old (>20 y) RM with recombinant simian IL-7 (rsIL-7)
results in only transient increases in peripheral CD4(+) and CD8(+) TN numbers
with no long-term benefit, even with repeated therapy. This transient effect was
due to peripheral TN expansion and not enhanced thymic function, and appeared to
be limited by induction of IL-7 nonresponsiveness. However, rsIL-7 therapy had a
more promising effect on the central memory T cell (TCM) population (both CD4(+)
and CD8(+)) in adult and old RM, doubling the numbers of these cells in
circulation and maintaining this larger population long term. IL-7 therapy did
not reduce TCR diversity of the memory T cell compartment, suggesting that rsIL-7
induced expansion was symmetrical. Thus, although rsIL-7 failed to counter age
associated TN loss, the ability of this therapy to expand clonotypically diverse
CD4(+) and CD8(+) TCM populations might potentially improve adaptive immune
responsiveness in the elderly.
PMID- 26416283
TI - Protein Tyrosine Phosphatase SHP-1 Modulates T Cell Responses by Controlling Cbl
b Degradation.
AB - Previously, we demonstrated that CD28 and CTLA-4 signaling control Casitas-B
lineage lymphoma (Cbl)-b protein expression, which is critical for T cell
activation and tolerance induction. However, the molecular mechanism(s) of this
regulation remains to be elucidated. In this study, we found that Cbl-b fails to
undergo tyrosine phosphorylation upon CD3 stimulation because SHP-1 is recruited
to and dephosphorylates Cbl-b, whereas CD28 costimulation abrogates this
interaction. In support of this finding, T cells lacking SHP-1 display heightened
tyrosine phosphorylation and ubiquitination of Cbl-b upon TCR stimulation, which
correlates with decreased levels of Cbl-b protein. The aberrant Th2 phenotype
observed in T cell-specific Shp1(-/-) mice is reminiscent of heightened Th2
response in Cblb(-/-) mice. Indeed, overexpressing Cbl-b in T cell-specific Shp1(
/-) T cells not only inhibits heightened Th2 differentiation in vitro, but also
Th2 responses and allergic airway inflammation in vivo. Therefore, SHP-1
regulates Cbl-b-mediated T cell responses by controlling its tyrosine
phosphorylation and ubiquitination.
PMID- 26416284
TI - Synthesis and Characterization of PLGA Shell Microcapsules Containing Aqueous
Cores Prepared by Internal Phase Separation.
AB - The preparation of microcapsules consisting of poly(D,L-lactide-co-glycolide)
(PLGA) polymer shell and aqueous core is a clear challenge and hence has been
rarely addressed in literature. Herein, aqueous core-PLGA shell microcapsules
have been prepared by internal phase separation from acetone-water in oil
emulsion. The resulting microcapsules exhibited mean particle size of 1.1 +/-
0.39 MUm (PDI = 0.35) with spherical surface morphology and internal poly-nuclear
core morphology as indicated by scanning electron microscopy (SEM). The
incorporation of water molecules into PLGA microcapsules was confirmed by
differential scanning calorimetry (DSC). Aqueous core-PLGA shell microcapsules
and the corresponding conventional PLGA microspheres were prepared and loaded
with risedronate sodium as a model drug. Interestingly, aqueous core-PLGA shell
microcapsules illustrated 2.5-fold increase in drug encapsulation in comparison
to the classical PLGA microspheres (i.e., 31.6 vs. 12.7%), while exhibiting
sustained release behavior following diffusion-controlled Higuchi model. The
reported method could be extrapolated to encapsulate other water soluble drugs
and hydrophilic macromolecules into PLGA microcapsules, which should overcome
various drawbacks correlated with conventional PLGA microspheres in terms of drug
loading and release.
PMID- 26416285
TI - High Rates of Diabetes Mellitus, Pre-diabetes and Obesity Among Somali Immigrants
and Refugees in Minnesota: A Retrospective Chart Review.
AB - We examined the prevalence of cardiovascular risk factors among Somali refugees
at a midwestern hospital in the U.S. This was a retrospective cohort study of
1007 adult Somali patients and an age and frequency-matched cohort of non-Somali
patients actively empanelled to a large, academic primary care practice network
in the Midwest United States between January 1, 2011 and December 31, 2012.
Cardiovascular risk factors were obtained by chart review and compared between
the two cohorts using a Chi squared test. Median age was 35 years (Q1, Q3; 27,
50). The prevalence of diabetes was significantly higher among Somali versus non
Somali patients (12.1 vs 5.3 %; p = 0.0001), as was prediabetes (21.3 vs 17.2 %;
p < 0.02) and obesity (34.6 vs 32.1 %; p = 0.047). After adjusting for age, sex,
body mass index, education and employment, among the Somali patients, the odds
ratio (95 % confidence interval) for diabetes was 2.78 (1.76-4.40) and 1.57 (1.16
2.13) for pre-diabetes. There was a significantly higher prevalence of diabetes,
pre-diabetes and obesity among Somali patients compared with non-Somali patients.
Further research into the specific causes of these disparities and development of
targeted effective and sustainable interventions to address them is needed.
PMID- 26416287
TI - Increasing fruit and vegetable intake: where are we at and how do we reach
recommendations?
PMID- 26416286
TI - A streamlined search technology for identification of synergistic drug
combinations.
AB - A major key to improvement of cancer therapy is the combination of drugs. Mixing
drugs that already exist on the market may offer an attractive alternative. Here
we report on a new model-based streamlined feedback system control (s-FSC)
method, based on a design of experiment approach, for rapidly finding optimal
drug mixtures with minimal experimental effort. We tested combinations in an in
vitro assay for the viability of a renal cell adenocarcinoma (RCC) cell line, 786
O. An iterative cycle of in vitro testing and s-FSC analysis was repeated a few
times until an optimal low dose combination was reached. Starting with ten drugs
that target parallel pathways known to play a role in the development and
progression of RCC, we identified the best overall drug combination, being a
mixture of four drugs (axitinib, erlotinib, dasatinib and AZD4547) at low doses,
inhibiting 90% of cell viability. The removal of AZD4547 from the optimized drug
combination resulted in 80% of cell viability inhibition, while still maintaining
the synergistic interaction. These optimized drug combinations were significantly
more potent than monotherapies of all individual drugs (p < 0.001, CI < 0.3).
PMID- 26416288
TI - Factors within the family environment such as parents' dietary habits and fruit
and vegetable availability have the greatest influence on fruit and vegetable
consumption by Polish children.
AB - OBJECTIVE: To identify determinants of fruit and vegetable (F&V) consumption
among school-aged children. DESIGN: A survey study was conducted in October 2010.
The questionnaire contained questions concerning social and demographic data,
lifestyle and dietary habits, particularly the frequency of F&V consumption,
availability of F&V and knowledge about recommended amounts of F&V intake.
SETTING: Polish primary schools. SUBJECTS: Children (n 1255) aged 9 years from
randomly selected primary schools and their parents. RESULTS: The children's
consumption of fruit and of vegetables was influenced by the fruit consumption
and vegetable consumption of their parents (r=0.333 and r=0.273, respectively;
P=0.001), parents encouraging their children to eat F&V (r=0.259 and r=0.271,
respectively; P=0.001), giving children F&V to take to school (r=0.338 and
r=0.321, respectively; P=0.001) and the availability of F&V at home (r=0.200 and
r=0.296, respectively; P=0.001). Parental education influenced only the frequency
of fruit consumption (r=0.074; P=0.01). A correlation between parents' knowledge
of the recommended intakes and the frequency of vegetable and fruit consumption
by children was noticed (r=0.258 and r=0.192, respectively, P=0.001).
CONCLUSIONS: Factors within the family environment such as parents' dietary
habits and F&V availability had the greatest influence on the F&V consumption by
children. Educational activities aimed at parents are crucial to increase the
consumption of F&V among children.
PMID- 26416289
TI - Assessing the cross-sectional and inter-temporal validity of the Household Food
Insecurity Access Scale (HFIAS) in Burundi.
AB - OBJECTIVE: To examine the cross-sectional and inter-temporal validity of the
Household Food Insecurity Access Scale (HFIAS) for rural households in Burundi.
DESIGN: Longitudinal survey about food security and agricultural production,
individually administered by trained interviewers in June 2007 and 2012. SETTING:
Ngozi, north of Burundi. SUBJECTS: Three hundred and fourteen household heads
were interviewed. RESULTS: Tobit models showed that the HFIAS was significantly
correlated with objective measures of food security, in this case total annual
food production (P<0.01), livestock keeping (P<0.01) and coffee production
(P<0.01) in both 2007 and 2012. This confirms that the HFIAS is cross-sectionally
valid and corroborates the findings of previous studies. However, while total
food production decreased by more than 25 % in terms of energy between 2007 and
2012, households reported an improvement in their perceived food security over
the same period, with the HFIAS decreasing from 13.9 to 10.8 (P<0.001). This
finding questions the inter-temporal validity of the HFIAS. It may be partly
explained through response shifts, in which households assess their own food
security status in comparison to that of their peers. CONCLUSIONS: The evidence
from our study suggests that the HFIAS is cross-sectionally valid, but may not be
inter-temporally valid, and should not be used as a single indicator to study
temporal trends in food security.
PMID- 26416290
TI - Using nutrient profiling to prevent misleading food marketing.
PMID- 26416293
TI - Generalized eczema craquele (asteatotic dermatitis) associated with pemetrexed
treatment.
PMID- 26416291
TI - Late radiation side effects, cosmetic outcomes and pain in breast cancer patients
after breast-conserving surgery and three-dimensional conformal radiotherapy :
Risk-modifying factors.
AB - BACKGROUND AND PURPOSE: The purpose of this work was to identify parameters
influencing the risk of late radiation side effects, fair or poor cosmetic
outcomes (COs) and pain in breast cancer patients after breast-conserving therapy
(BCT) and three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND
METHODS: Between 2006 and 2013, 159 patients were treated at the Hannover Medical
School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain
were assessed by multivariate analysis. RESULTS: LENT-SOMA grade 1-4 toxicity was
observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and
breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe
breast pain, and 21.4 % complained about moderate or severe pain in the arm or
shoulder. In multivariate analysis, axillary clearing (AC) was significantly
associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 %
confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated
with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or
pseudoptosis and a bra size >= cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A
ptosis grade 2/3 or pseudoptosis and a bra size >= cup C were the parameters
significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2
8.4). Concerning chronic breast pain, we found a trend related to the prescribed
radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164).
Chronic shoulder or arm pain was statistically significantly associated with
lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). CONCLUSION:
Chronic arm and breast oedema were significantly influenced by the extent of
surgery (AC). Ptotic and large breasts were significantly associated with
unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain
were not associated with radiotherapy parameters.
PMID- 26416294
TI - Resistance to Streptomyces turgidiscabies in potato involves an early and
sustained transcriptional reprogramming at initial stages of tuber formation.
AB - Common scab, caused by species from the bacterial genus Streptomyces, is an
important disease of potato (Solanum tuberosum) crops worldwide. Early
tuberization is a critical period for pathogen infection; hence, studies of host
gene expression responses during this developmental stage can be important to
expand our understanding of the infection process and to identify putative
resistance genes. In an infection experiment with the highly susceptible potato
cultivar Saturna and the relatively resistant cultivar Beate, transcription
profiles were obtained by RNA sequencing at two developmental stages: the early
hook stage and the early tuber formation stage. Our results indicate that 'Beate'
mounts an early and sustained response to infection by S. turgidiscabies, whereas
the defence response by 'Saturna' ceases before the early tuber formation stage.
Most pronounced were the putative candidate defence-associated genes uniquely
expressed in 'Beate'. We observed an increase in alternative splicing on pathogen
infection at the early hook stage for both cultivars. A significant down
regulation of genes involved in the highly energy-demanding process of ribosome
biogenesis was observed for the infected 'Beate' plants at the early hook stage,
which may indicate an allocation of resources that favours the expression of
defence-related genes.
PMID- 26416297
TI - Longitudinal domain wall formation in elongated assemblies of ferromagnetic
nanoparticles.
AB - Through evaporation of dense colloids of ferromagnetic ~13 nm epsilon-Co
particles onto carbon substrates, anisotropic magnetic dipolar interactions can
support formation of elongated particle structures with aggregate thicknesses of
100-400 nm and lengths of up to some hundred microns. Lorenz microscopy and
electron holography reveal collective magnetic ordering in these structures.
However, in contrast to continuous ferromagnetic thin films of comparable
dimensions, domain walls appear preferentially as longitudinal, i.e., oriented
parallel to the long axis of the nanoparticle assemblies. We explain this unusual
domain structure as the result of dipolar interactions and shape anisotropy, in
the absence of inter-particle exchange coupling.
PMID- 26416295
TI - Meta-analysis of risk factors for nonsuicidal self-injury.
AB - Nonsuicidal self-injury (NSSI) is a prevalent and dangerous phenomenon associated
with many negative outcomes, including future suicidal behaviors. Research on
these behaviors has primarily focused on correlates; however, an emerging body of
research has focused on NSSI risk factors. To provide a summary of current
knowledge about NSSI risk factors, we conducted a meta-analysis of published,
prospective studies longitudinally predicting NSSI. This included 20 published
reports across 5078 unique participants. Results from a random-effects model
demonstrated significant, albeit weak, overall prediction of NSSI (OR=1.59; 95%
CI: 1.50 to 1.69). Among specific NSSI risk factors, prior history of NSSI,
cluster b, and hopelessness yielded the strongest effects (ORs>3.0); all
remaining risk factor categories produced ORs near or below 2.0. NSSI
measurement, sample type, sample age, and prediction case measurement type (i.e.,
binary versus continuous) moderated these effects. Additionally, results
highlighted several limitations of the existing literature, including
idiosyncratic NSSI measurement and few studies among samples with NSSI histories.
These findings indicate that few strong NSSI risk factors have been identified,
and suggest a need for examination of novel risk factors, standardized NSSI
measurement, and study samples with a history of NSSI.
PMID- 26416298
TI - Dynamic blood flow to the retrograde limb of the internal mammary vein in breast
reconstruction with free flap.
AB - BACKGROUND: In free flap breast reconstruction, the retrograde limb of the
internal mammary vein (IMV) is occasionally used as a second recipient vein. In
this study, we evaluated the dynamic blood flow to the retrograde limb of the IMV
(retrograde IMV) at the anastomosed site via indocyanine green (ICG) angiography
METHODS: In 40 patients undergoing free flap breast reconstruction, we evaluated
the dynamic blood flow as "stain(+)" if a stain by ICG was observed and,
"flow(+)" if a smooth blood flow was recognized. RESULTS: Based on the ICG
angiography, "stain(+)" was observed in all cases, but "flow(+)" was detected in
only 72.5% of the cases. There was no severe complication. CONCLUSION: This study
shows that thrombosis is prone to occur in the second recipient vein in the 27.5%
of the cases with no smooth flow, and therefore, the retrograde IMV may not
function as a back-up in these cases.
PMID- 26416299
TI - Structure and Activity Changes of Phytohemagglutinin from Red Kidney Bean
(Phaseolus vulgaris) Affected by Ultrahigh-Pressure Treatments.
AB - Phytohemagglutin (PHA), purified from red kidney beans (Phaseolus vulgaris) by
Affi-Gel blue affinity chromatography, was subjected to ultrahigh-pressure (UHP)
treatment (150, 250, 350, and 450 MPa). The purified PHA lost its
hemagglutination activity after 450 MPa treatment and showed less pressure
tolerance than crude PHA. However, the saccharide specificity and alpha
glucosidase inhibition activity of the purified PHA did not change much after UHP
treatment. Electrophoresis staining by periodic acid-Schiff (PAS) manifested that
the glycone structure of purified PHA remained stable even after 450 MPa pressure
treatment. However, electrophoresis staining by Coomassie Blue as well as
circular dichroism (CD) and differential scanning calorimetry (DSC) assay proved
that the protein unit structure of purified PHA unfolded when treated at 0-250
MPa but reaggregates at 250-450 MPa. Therefore, the hemagglutination activity
tends to be affected by the protein unit structure, while the stability of the
glycone structure contributed to the remaining alpha-glucosidase inhibition
activity.
PMID- 26416300
TI - Recent progress for the synthesis of selected carbocyclic nucleosides.
AB - Nucleoside analogs are extremely useful for the development of therapeutic agents
to control viral diseases and cancer. Among the numerous modifications on the
nucleoside skeleton, replacement of the oxygen of the furanose ring by a CH2
group resulted in increased flexibility and higher resistance to phosphorylases
and led to carbocyclic nucleoside analogs (or carbanucleosides). The broad
spectrum of biological activities of carbocyclic nucleosides led to tremendous
research interest in their syntheses. The article documents recent strategies for
the synthesis of active carbocyclic nucleosides by presenting individual case
studies, such as the neplanocins, entecavir and selected fluorinated carbocyclic
nucleosides. Furthermore, it provides new insights into new directions for more
potent and active carbocyclic nucleoside analogs.
PMID- 26416301
TI - Bronchioalveolar morphogenesis of human bronchial epithelial cells depending upon
hepatocyte growth factor.
AB - Lung alveolar regeneration occurs in adult human lungs as a result of
proliferation, differentiation and alveolar morphogenesis of stem cells. It is
increasingly being believed that bronchial epithelial cells (BECs) have a
potential as stem cells, because they are potent to differentiate into multiple
central and peripheral lung cell types in three-dimensional (3D) cultures, and
they develop multiple foci with well-differentiated histogenesis after
transformed into neoplastic cells. In this study, we investigated morphogenic
abilities of HBE135 human BECs immortalized by E6/E7 oncogene in 3D cultures.
When HBE135 cells were cultured alone or co-cultured with endothelial cells, the
cells formed spherical colonies without branching. However, in co-culture with
lung fibroblast MRC-9 cells, HBE135 cells formed colonies with bronchioalveolar
like complex branching, suggesting that MRC-9-derived soluble factor(s) are
responsible for the branching formation. MRC-9 cells, not endothelial cells, were
found to highly express hepatocyte growth factor (HGF), a soluble molecule
involved in liver and kidney regeneration. An anti-HGF neutralizing antibody
severely suppressed the complex branching formation, but addition of HGF could
not sufficiently compensate the morphogenic effects of MRC-9 cells, suggesting
that MCR-9-derived HGF was necessary but insufficient for the bronchioalveolar
structure formation. Immunohistochemistry revealed that Met, a cognate receptor
for HGF, was highly expressed and phosphorylated in neoplastic BECs from lung
adenocarcinomas with well-differentiated, not poorly differentiated,
histogenesis. These results are consistent with the notion that BECs have an
aspect of stem cells. This aspect appears to become manifest through HGF-Met
signalling pathway activation.
PMID- 26416302
TI - Education and training for implementation science: our interest in manuscripts
describing education and training materials.
AB - Alongside the growth in interest in implementation science, there has been a
marked increase in training programs, educational courses, degrees, and other
offerings in implementation research and practice to meet the demand for this
expertise. We believe that the science of capacity building has matured but that
we can advance it further by shining light on excellent work in this area and by
highlighting gaps for future research. At Implementation Science, we regularly
receive manuscripts that describe or evaluate training materials, competencies,
and competency development in implementation curricula. We are announcing a
renewed interest in manuscripts in this area, with specifications described
below.
PMID- 26416303
TI - Can pretreatment serum calcium level predict the efficacy of methotrexate in the
treatment of severe plaque psoriasis?
AB - BACKGROUND: The efficacy of methotrexate (MTX) varies in the treatment of
psoriasis. OBJECTIVE: We sought to identify an indicator from routine
pretreatment tests to predict MTX efficacy in the treatment of psoriasis.
METHODS: In a retrospective analysis of 77 psoriatic patients, the correlation
between MTX efficacy and pretreatment routine test results was analyzed with
Spearman correlation. The potential risks were further evaluated with a linear
regression model. Receiver operating characteristic analysis was performed to
examine the effectiveness of serum total calcium (tCa) to predict the effect of
MTX on psoriasis. The highest Youden index was used to determine the cutoff
point, with which the positive and negative predictive values were calculated.
Synergistic effects of MTX and calcium on keratinocyte growth and psoriasis-like
mouse model were also investigated. RESULTS: The pretreatment tCa level exhibited
the closest association with MTX efficacy. The relative psoriasis improvement
with tCa was 61.07% (95% confidence interval, 42.85-79.29; P < .001) and better
improvements were observed in patients with higher tCa (r = 0.588; P < .002). MTX
inhibited keratinocyte growth, which was enhanced synergistically by calcium. In
a psoriasis-like mouse model, MTX strongly inhibited epidermis proliferation in
the high-calcium group. LIMITATIONS: One limitation of our study is the
relatively small sample size. CONCLUSION: Pretreatment tCa level has the highest
correlation with MTX efficacy, which might be useful in predicting beneficial
treatment results in psoriasis. Larger studies are required to confirm our
findings.
PMID- 26416305
TI - Epidemiology of uraemic itch: New data.
AB - Chronic itch (CI) is a frequent and impairing symptom in haemodialysis (HD)
patients. Within the last decades, worldwide variations were reported in the
prevalence of itch in HD patients, ranging from 10 to 77%. Regional differences
and especially the irregular pattern of itch in HD may explain why CI is still
not well perceived and underestimated in HD patients. The pathogenesis is still
unclear and therapy is ineffective in the majority of cases. There is a great
diversity of prevalence estimates of itch used in different studies as well, as
the study population greatly differs, especially when investigating CI in HD. Due
to the demographic situation with a rising number of aged patients and increasing
survival rates in HD, the number of HD patients will continuously grow,
especially in the Western countries. Up to now, representative epidemiological
data on CI in HD were missing. GEHIS (German Epidemiological Hemodialysis Itch
Study) was established in 2012 as a representative prospective cross-sectional
study. Eight hundred and sixty HD patients from a randomly selected cluster
sample were included. The primary outcome measures were different prevalence
measures of CI. The point prevalence was 25.2%, the 12-month prevalence was 27.2%
and the lifetime prevalence of CI was 35.2%. General health status and health
related quality of life (HRQOl) were significantly impaired in those with CI. Due
to the comparability of standards in HD quality, these results can be transferred
to Western countries. This study demonstrates that CI is a frequent, long-lasting
burden in HD patients affecting every fourth HD patient (point prevalence) and
more than every third HD patient at some point in their lifetime.
PMID- 26416304
TI - Associations between the prevalence of influenza vaccination and patient's
knowledge about antibiotics: a cross-sectional study in the framework of the
APRES-project in Austria.
AB - BACKGROUND: This study aimed to identify associations between GP patient's
knowledge about the spectrum of effectiveness of antibiotics and the probability
of vaccination against influenza. The underlying hypothesis was that individuals
with an understanding that antibiotics are ineffective against viruses, common
colds, and flu were more likely to be vaccinated than persons lacking this
knowledge. METHODS: This cross-sectional study was conducted within the context
of the European APRES project in Austria. Between November 2010 and July 2011,
patients were recruited from GP practices to complete questionnaires about their
knowledge about antibiotics and their influenza vaccination status. Statistical
analyses included subgroup analyses and logistic regression models. RESULTS: Data
of 3224 patients was analyzed, demonstrating that patients with better knowledge
concerning antibiotics had a significantly higher likelihood of being vaccinated
(OR 1.35, CI 95 % 1.18-1.54). While the overall vaccination rate was low (18.6 %
in 2009/2010 and 14.0 % in 2010/2011), elderly compared to younger adults (OR
0.06 CI 95 % 0.03-0.13) and healthcare workers (OR 2.24, CI 95 % 1.42-3.54)
demonstrated higher likelihood of vaccination. Additionally, female GPs had
significantly more vaccinated patients than male GPs (OR 2.90, CI 95 % 1.32
6.40). DISCUSSION: There has been little prior study on the association between a
patient's knowledge of the effectiveness spectrum of antibiotics and influenza
vaccination status. Given the public health imperative to increase annual
prevalence of influenza vaccination, understanding this educational gap can
improve specificity in counseling as well as vaccination rates. Ultimately, we
found that those with a better knowledge on about antibiotics had a significantly
higher likelihood of being vaccinated. CONCLUSIONS: The results of this study
demonstrate that vaccination prevalence is associated with patient's knowledge
about antibiotics. It can be concluded that one strategy to improve the overall
low vaccination rates for seasonal influenza in Austria would be, particularly
for male GPs, to have a specific discussion with patients about these
circumstances by focusing on younger patients. Further, public health efforts
could supplement in-office strategies to improve this area of health literacy.
PMID- 26416306
TI - Periodontal-disease-associated biofilm: A reservoir for pathogens of medical
importance.
AB - The ecological diversity of the periodontal microenvironment may provide suitable
conditions for the colonization of species not usually considered members of the
oral microbiota. In this investigation, we aimed to determine the prevalence and
levels of pathogenic species of medical relevance in the microbiota of
individuals with distinct periodontal clinical status. Subgingival biofilm was
obtained from patients with periodontal health (H, n = 81), gingivitis (G, n =
55), generalized aggressive (AgP, n = 36) or chronic periodontitis (CP, n = 98),
and analyzed for 39 microbial taxa using a checkerboard DNA-DNA hybridization
technique. Microbial differences among groups, as well as associations between
clinical and microbiological parameters were sought by non-parametric and
univariate correlation tests. Neisseria spp., Peptostreptococus anaerobius,
Candida albicans, enterobacteria, Pseudomonas aeruginosa, Eubacterium saphenum,
Clostridium difficile and Olsenella uli were detected in high mean prevalence and
counts in the subgingival microbiota of the study population. Species that were
more related to periodontal inflammation and tissue destruction at the patient
and site levels included enterobacteria, C. albicans, Neisseria spp., P.
aeruginosa, O. uli, Hafnia alvei, Serratia marcescens and Filifactor alocis (p <
0.05). In contrast, Fusobacterium necrophorum, Lactobacillus acidophilus,
Staphylococcus aureus and Streptococcus pneumoniae were associated with
periodontal health (p < 0.05). Pathogenic species of medical importance may be
detected in high prevalence and levels in the periodontal microbiota. Regardless
of their role in periodontal health or disease, the periodontal biofilm may be a
source for dissemination and development of systemic infections by these
pathogenic microorganisms.
PMID- 26416307
TI - Host antioxidant enzymes and TLR-2 neutralization modulate intracellular survival
of Staphylococcus aureus: Evidence of the effect of redox balance on host
pathogen relationship during acute staphylococcal infection.
AB - Staphylococcus aureus is an important pathogen in bone disease and innate immune
recognition receptor, TLR-2 is reported to be crucial for inflammatory bone loss.
Role of TLR-2 in bacterial clearance and cytokine response to S. aureus infection
in murine bone marrow macrophages has been reported but the role of host derived
ROS in host-pathogen relationship still remains an obvious question. In the
present study, blocking of SOD and catalase in TLR-2 neutralized fresh bone
marrow cells (FBMC) with Diethyldithiocarbamic acid (DDC) and 3-Amino-1,2,4
triazole (ATZ), separately, during acute S. aureus infection, produces moderate
level of ROS and limits inflammation as compared with only TLR-2 non-neutralized
condition and leads to decreased bacterial count compared with only TLR-2
neutralized condition. In summary, host SOD and catalase modulates ROS
generation, cytokine levels and TLR-2 expression in FBMCs during acute S. aureus
infection which might be useful in the alleviation of S. aureus infection and
bone loss.
PMID- 26416308
TI - Qualitative and quantitative pharmacophore-similarity assessment of
anthranilamide-based factor Xa inhibitors: applications on similar molecules with
identical biological endpoints.
AB - It is a conventional practice to exclude molecules with identical biological
endpoints to avoid bias in the resulting hypothesis model. Despite the diverse
chemical functionalities, the receptor interactions of such molecules are often
unexplored. The present study motivates the selection of these molecules
diversified by single atom or functional group compared to internal molecules as
external set and helps in the understanding of corresponding effects toward
receptor interactions and biological endpoints. Applied on anthranilamide-series
of factor Xa analogs, the inhibitory activities were correlated (r(2) = 0.99) and
validated (q(2) = 0.68) with distance-based pharmacophore descriptors using
support vector machine. The selected external set molecules exhibited better
prediction accuracy by securing activities less than one residual threshold. The
effect on inhibitory activity was assessed by the examination of pharmacophore
similarity and its interactions with key residues of Human factor Xa enzyme using
molecular docking approach. Furthermore, qualitative pharmacophore models were
developed on the subset of molecular dataset divided as most actives, moderately
actives and least actives, to recognize crucial activity governing pharmacophore
features. The outcome of this study will bring new insights about the
requirements of pharmacophore features and prioritizes its selection in the
design and optimization of potent Xa inhibitors.
PMID- 26416309
TI - Gene expression: Environmental noise control.
PMID- 26416310
TI - Epigenetics: Bad Karma reduces palm oil yields.
PMID- 26416313
TI - Effects of composition modulation on the luminescence properties of Eu(3+) doped
Li1-xAgxLu(MoO4)2 solid-solution phosphors.
AB - Double molybdate scheelite-type solid-solution phosphors Li1-xAgxLu1
y(MoO4)2:yEu(3+) were synthesized by the solid state reaction method, and their
crystal structures and luminescence properties were investigated in detail. The
composition modulation and structural evolution of this series of samples were
studied and the selected AgEu(MoO4)2, AgLu(MoO4)2, LiLu(MoO4)2 and LiEu(MoO4)2
phases were analyzed based on the Rietveld refinement. Depending on the variation
of the Li/Ag ratio in Li1-xAgxLu1-y(MoO4)2:yEu(3+) phosphors, the difference in
the luminescence properties of Li1-xAgxLu1-y(MoO4)2:yEu(3+) phosphors was
ascribed to two factors, one reason could be assigned to the coupling effect and
the nonradiative transition between the energy levels of LixAg1-xLu(MoO4)2
matrices and the activator Eu(3+), another could be due to the near ultraviolet
energy absorption and transmission efficiency between the charge-transfer (CT)
band of O(2-)-Mo(6+) and the 4f -> 4f emissive transitions of Eu(3+). The
ultraviolet-visible diffuse reflection spectra (UV-vis DRS) and Raman spectra
analysis were also used to verify the above mechanism.
PMID- 26416311
TI - Molecular insights into transgenerational non-genetic inheritance of acquired
behaviours.
AB - Behavioural traits in mammals are influenced by environmental factors, which can
interact with the genome and modulate its activity by complex molecular
interplay. Environmental experiences can modify social, emotional and cognitive
behaviours during an individual's lifetime, and result in acquired behavioural
traits that can be transmitted to subsequent generations. This Review discusses
the concept of, and experimental support for, non-genetic transgenerational
inheritance of acquired traits involving the germ line in mammals. Possible
mechanisms of induction and maintenance during development and adulthood are
considered along with an interpretation of recent findings showing the
involvement of epigenetic modifications and non-coding RNAs in male germ cells.
PMID- 26416312
TI - Multi-modality image-based computational analysis of haemodynamics in aortic
dissection.
AB - Aortic dissection is a disease whereby an injury in the wall of the aorta leads
to the creation of a true lumen and a false lumen separated by an intimal flap
which may contain multiple communicating tears between the lumina. It has a high
associated morbidity and mortality, but at present, the timing of surgical
intervention for stable type B dissections remains an area of debate. Detailed
knowledge of haemodynamics may yield greater insight into the long-term outcomes
for dissection patients by providing a greater understanding of pressures, wall
shear stress and velocities in and around the dissection. In this paper, we aim
to gather further insight into the complex haemodynamics in aortic dissection
using medical imaging and computational fluid dynamics modelling. Towards this
end, several computer models of the aorta of a patient presenting with an acute
Stanford type B dissection were created whereby morphometric parameters related
to the dissection septum were altered, such as removal of the septum, and the
variation of the number of connecting tears between the lumina. Patient-specific
flow data acquired using 2D PC-MRI in the ascending aorta were used to set the
inflow boundary condition. Coupled zero-dimensional (Windkessel) models
representing the distal vasculature were used to define the outlet boundary
conditions and tuned to match 2D PC-MRI flow data acquired in the descending
aorta. Haemodynamics in the dissected aorta were compared to those in an
equivalent 'healthy aorta', created by virtually removing the intimal flap
(septum). Local regions of increased velocity, pressure, wall shear stress and
alterations in flow distribution were noted, particularly in the narrow true
lumen and around the primary entry tear. The computed flow patterns compared
favourably with those obtained using 4D PC-MRI. A lumped-parameter heart model
was subsequently used to show that in this case there was an estimated 14 %
increase in left ventricular stroke work with the onset of dissection. Finally,
the effect of secondary connecting tears (i.e. those excluding the primary entry
and exit tears) was also studied, revealing significant haemodynamic changes when
no secondary tears are included in the model, particularly in the true lumen
where increases in flow over [Formula: see text] and drops in peak pressure of 18
% were observed.
PMID- 26416314
TI - History note: tragedy of Thorotrast.
PMID- 26416315
TI - Evaluation of a school screening programme for young people from refugee
backgrounds.
AB - AIM: To describe the development of the Optimising Health and Learning Program,
guided by the only available published framework for the delivery of health
services to newly arrived refugee children and report on the evaluation of the
programme. METHODS: We conducted process and impact evaluation using a mixed
methods approach. The sample was 294 refugee young people enrolled in two
Intensive English Centres in New South Wales. We collected quantitative data
(demographic and clinical information) as well as qualitative data via focus
groups, key informant interviews, surveys and programme documentation.
Qualitative data were subjected to thematic analysis; programme documents
underwent document review. RESULTS: There were high levels of programme
participation (90%), and the yield from routine health screening was high (80% of
participants screened positive for two or more health conditions). All identified
programme development strategies were implemented; programme partners and
participants reported satisfaction with the programme. Sixteen programme partners
were identified with a high level of intersectoral collaboration reported.
Significant in-kind contributions and seed funding enabled the uptake of the
programme to increase from one to five Intensive English Centres over a 4-year
period. CONCLUSION: Process and impact evaluation identified that the programme
was well implemented and met its stated objectives of increasing the detection of
health conditions likely to impact on student health and learning; linkage of
newly arrived students and their families with primary health care; and
coordination of care across primary health and specialist services.
PMID- 26416316
TI - Direct infection of primary endothelial cells with human cytomegalovirus
prevents angiogenesis and migration.
AB - Human cytomegalovirus (hCMV) is a beta herpesvirus that establishes lifelong
infection. Although the virus does not usually cause overt clinical symptoms in
immunocompetent individuals it can have deleterious effects in immunocompromised
patients, such as those on post-transplant medication or with HIV infection. hCMV
is the most common congenital infection and can lead to serious fetal sequelae.
Endothelial cells (ECs) are natural hosts for hCMV in vivo, therefore,
investigations of how this cell type is modulated by infection are key to
understanding hCMV pathogenesis. Previous studies have examined the effect of
secretomes from hCMV-infected cells on EC angiogenesis, whereas the effect of
direct infection on this process has not been so well investigated. Here, we show
that placental ECs are viral targets during congenital infection and that vessels
in infected tissue appear morphologically abnormal. We demonstrate that the
clinical hCMV strain VR1814 impaired EC tube assembly in in vitro angiogenesis
assays and inhibited wound healing ability in scratch assays. Secretomes from
infected cultures did not impair angiogenesis of uninfected ECs, suggesting that
cell-intrinsic changes, as opposed to secreted factors, were responsible. We
observed viral gene transcription dependent downregulation of the expression of
angiogenesis-associated genes, including angiopoietin-2, TEK receptor and
vascular endothelial growth factor receptors. An alternative clinical hCMV stain,
TB40E showed similar effects on EC angiogenesis. Together, our data indicate that
direct infection with hCMV can induce an anti-migratory and anti-angiogenic EC
phenotype, which could have a detrimental effect on the vasculature development
in infected tissues.
PMID- 26416317
TI - Distribution and immunotoxicity by intravenous injection of iron nanoparticles in
a murine model.
AB - With the increased application of iron oxide nanoparticles (FeNPs) for biomedical
imaging purposes, concerns regarding the onset of the unexpected adverse health
effects following exposure have been rapidly raised. In this study, we
investigated the tissue distribution and immunotoxicity of FeNPs (2 and 4 mg kg(
1)) over time (2, 4 and 13 weeks) after single intravenous injection. At 13 weeks
after a single injection, the iron levels increased in all measured tissues
compared to the control, and iron accumulation was notable in the liver, spleen
and thymus. These changes were accompanied by changes in levels of redox reaction
related elements, including copper, manganese, zinc and cobalt. In addition, as
compared to the control, the number of white blood cells and percentage of
neutrophils significantly increased in the treated groups, and the interleukin-8
secretion and lactate dehydrogenase release were clearly elevated in the treated
groups along with enhanced expressions of chemotaxis-related proteins. However,
expression of antigen presenting related proteins attenuated following
accumulation of FeNPs. Taken together, we suggest that FeNPs may primarily induce
toxicity in the liver and immune system, and immunotoxicological evaluation
should be considered to predict adverse health effects following exposure to NPs.
PMID- 26416318
TI - Microdemographic Determinants of Population Recovery among the Northern Ache.
AB - A pattern of population crash and rapid recovery is a common feature of the
pacification and settlement experience of the indigenous peoples of tropical
South America. Despite the obvious importance of these events to the demographic
and anthropological sciences as a whole, as well as their significant practical
implications, little is known about the microdemographic determinants of these
paired phenomena. Using methods of asymptotic and stochastic demographic
analysis, we reconstructed the microdemographic drivers of this history among one
indigenous population: the Northern Ache of eastern Paraguay. This article
explores the implications of these relationships for understanding the overall
demographic turnaround observed within similar groups, as well as for the future
trajectory of the Northern Ache in particular.
PMID- 26416319
TI - Mitochondrial DNA Suggests a Western Eurasian Origin for Ancient (Proto-)
Bulgarians.
AB - Ancient (proto-) Bulgarians have long been thought of as a Turkic population.
However, evidence found in the past three decades shows that this is not the
case. Until now, this evidence has not included ancient mitochondrial DNA (mtDNA)
analysis. To fill this void, we collected human remains from the 8th to the 10th
century AD located in three necropolises in Bulgaria: Nojarevo (Silistra region)
and Monastery of Mostich (Shumen region), both in northeastern Bulgaria, and
Tuhovishte (Satovcha region) in southwestern Bulgaria. The phylogenetic analysis
of 13 ancient DNA samples (extracted from teeth) identified 12 independent
haplotypes, which we further classified into mtDNA haplogroups found in present
day European and western Eurasian populations. Our results suggest a western
Eurasian matrilineal origin for proto-Bulgarians, as well as a genetic similarity
between proto- and modern Bulgarians. Our future work will provide additional
data that will further clarify proto-Bulgarian origins, thereby adding new clues
to the current understanding of European genetic evolution.
PMID- 26416320
TI - Identification of Whole Mitochondrial Genomes from Venezuela and Implications on
Regional Phylogenies in South America.
AB - Recent studies have expanded and refined the founding haplogroups of the Americas
using whole mitochondrial (mtDNA) genome analysis. In addition to pan-American
lineages, specific variants have been identified in a number of studies that show
higher frequencies in restricted geographical areas. To further characterize
Native American maternal lineages and specifically examine local patterns within
South America, we analyzed 12 maternally unrelated Yekuana whole mtDNA genomes
from one village (Sharamana) that include the four major Native American
haplogroups A2, B2, C1, and D1. Based on our results, we propose a
reconfiguration of one subhaplogroup A2 (A2aa) that is specific to South America
and identify other singleton branches across the four haplogroups. Furthermore,
we show nucleotide diversity values that increase from north to south for
haplogroups C1 and D1. The results from our work add to the growing mitogenomic
data that highlight local phylogenies and support the rapid genetic
differentiation of South American populations, which has been correlated with the
linguistic diversity in the region by previous studies.
PMID- 26416321
TI - Hemochromatosis: Niche Construction and the Genetic Domino Effect in the European
Neolithic.
AB - Hereditary hemochromatosis is caused by a potentially lethal recessive gene (HFE,
C282Y allele) that increases iron absorption and reaches polymorphic levels in
northern European populations. Because persons carrying the allele absorb iron
more readily than do noncarriers, it has often been suggested that HFE is an
adaptation to anemia. We hypothesize positive selection for HFE began during or
after the European Neolithic with the adoption of an iron-deficient high-grain
and dairying diet and consequent anemia, a finding confirmed in Neolithic and
later European skeletons. HFE frequency compared with rate of lactase persistence
in Eurasia yields a positive linear correlation coefficient of 0.86. We suggest
this is just one of many mutations that became common after the adoption of
agriculture.
PMID- 26416322
TI - Genetic Admixture and Flavor Preferences: Androstenone Sensitivity in Malagasy
Populations.
AB - The genetic basis of androstenone anosmia has been well studied due to
androstenone's putative role as a human sex pheromone and its presence in pork
meat. Polymorphisms have been identified on the olfactory receptor gene OR7D4,
which significantly affect perception of androstenone pleasantness and intensity
in several Western populations. This study aims to investigate androstenone
sensitivity and the influence of OR7D4 polymorphisms in non-Western populations.
Androstenone perception was tested in 132 individuals from Madagascar using a
double three-alternative choice test with two concentrations of androstenone
(0.17 and 1.7 ug/ml). We found that Malagasy populations described this molecule
in a similar way to European populations, and 21% of the sample was not able to
smell androstenone. In contrast to previous studies, there was no significant
evidence of the influence of rs61729907: C>T (R88W) and rs5020278: C>T
polymorphisms (T133M) on androstenone sensitivity in Malagasy populations. We
found, however, a significant effect of the polymorphism rs61732668 (P79L) and a
significant difference in androstenone perception between populations in
different locations across Madagascar. This study indicates the existence of
population-specific factors in androstenone sensitivity, suggesting that
population history has a role in shaping an individual's smell and flavor
preferences and food preferences in general.
PMID- 26416323
TI - Low Mitochondrial DNA Diversity in an Ancient Population from China: Insight into
Social Organization at the Fujia Site.
AB - To gain insight into the social organization of a population associated with the
Dawenkou period, we performed ancient DNA analysis of 18 individuals from human
remains from the Fujia site in Shandong Province, China. Directly radiocarbon
dated to 4800-4500 cal BP, the Fujia site is assumed to be associated with a
transitional phase from matrilineal clans to patrilineal monogamous families. Our
results reveal a low mitochondrial DNA diversity from the site and population.
Combined with Y chromosome data, the pattern observed at the Fujia site is most
consistent with a matrilineal community. The patterns also suggest that the bond
of marriage was de-emphasized compared with the bonds of descent at Fujia.
PMID- 26416325
TI - Supraesophageal reflux disease: solving a riddle wrapped in a mystery inside an
enigma.
PMID- 26416326
TI - Family history of colorectal cancer: it is time to rethink screening
recommendations.
PMID- 26416328
TI - Interaction between amiodarone and sofosbuvir-based treatment for hepatitis C
virus infection: potential mechanisms and lessons to be learned.
PMID- 26416327
TI - Interferon-gamma and Tumor Necrosis Factor-alpha Produced by T Cells Reduce the
HBV Persistence Form, cccDNA, Without Cytolysis.
AB - BACKGROUND & AIMS: Viral clearance involves immune cell cytolysis of infected
cells. However, studies of hepatitis B virus (HBV) infection in chimpanzees have
indicated that cytokines released by T cells also can promote viral clearance via
noncytolytic processes. We investigated the noncytolytic mechanisms by which T
cells eliminate HBV from infected hepatocytes. METHODS: We performed a cytokine
enzyme-linked immunosorbent assay of serum samples from patients with acute and
chronic hepatitis B. Liver biopsy specimens were analyzed by in situ
hybridization. HepG2-H1.3 cells, HBV-infected HepaRG cells, and primary human
hepatocytes were incubated with interferon-gamma (IFNgamma) or tumor necrosis
factor-alpha (TNF-alpha), or co-cultured with T cells. We measured markers of HBV
replication, including the covalently closed circular DNA (cccDNA). RESULTS:
Levels of IFNgamma and TNF-alpha were increased in serum samples from patients
with acute vs chronic hepatitis B and controls. In human hepatocytes with stably
replicating HBV, as well as in HBV-infected primary human hepatocytes or HepaRG
cells, IFNgamma and TNF-alpha each induced deamination of cccDNA and interfered
with its stability; their effects were additive. HBV-specific T cells, through
secretion of IFNgamma and TNF-alpha, inhibited HBV replication and reduced cccDNA
in infected cells without the direct contact required for cytolysis. Blocking
IFNgamma and TNF-alpha after T-cell stimulation prevented the loss of cccDNA.
Deprivation of cccDNA required activation of nuclear APOBEC3 deaminases by the
cytokines. In liver biopsy specimens from patients with acute hepatitis B, but
not chronic hepatitis B or controls, hepatocytes expressed APOBEC3A and APOBEC3B.
CONCLUSIONS: IFNgamma and TNF-alpha, produced by T cells, reduce levels of HBV
cccDNA in hepatocytes by inducing deamination and subsequent cccDNA decay.
PMID- 26416329
TI - Therapy with direct-acting antivirals for genotype 3 patients: interferon's last
gasp?
PMID- 26416330
TI - Diagnosing minimal hepatic encephalopathy: from the ivory tower to the real
world.
PMID- 26416331
TI - Deciphering the genetic code of gastrointestinal diseases among African
Americans.
PMID- 26416332
TI - Generation and flow cytometric quality control of clinical-scale
TCRalphabeta/CD19-depleted grafts.
AB - BACKGROUND: The depletion of TCRalphabeta+ T cells and CD19+ B cells is a graft
purification method for haploidentical stem cell transplantation (HSCT) retaining
stem cells, NK cells and TCRgammadelta+ T cells. To avoid treatment-related
occurrence of severe GvHD a precise quantification of residual TCRalphabeta+ T
cells in the graft is of essential importance. METHODS: Nine stem cell grafts
were purified immunomagnetically on a CliniMACS device and flow cytometric
quality control (QC) was performed before and after TCRalphabeta/CD19-depletion.
RESULTS: As a challenge a new 10-color QC-panel was established, which enables
accurate quantification of the graft composition. The binding sites of residual
TCRalphabeta+ T and CD19+ B cells were at least partly occupied by depletion
antibodies impeding flow cytometric analysis. Based on respective controls and an
assumed variation coefficient of 18%, the detection limit of residual
TCRalphabeta T cells was 1 cell/ul. and 0.002% of CD45+ cells. Log-depletion of
TCRalphabeta and CD19 cells was -3.9 and -3.3, respectively. The recovery was
82.1%, 67.1% and 72.7% for stem cells, NK cells and for TCRgammadelta+ T cells.
CONCLUSIONS: In clinical use this method may help to improve transplantation
outcome, due to the correct application of the desired stem cell and the limited
T cell dose. The panel is designed for the QC following TCRalphabeta/CD19
depletion but is adaptable to other depletion strategies as well. (c) 2015
International Clinical Cytometry Society.
PMID- 26416333
TI - Identification of an iridium(III) complex with anti-bacterial and anti-cancer
activity.
AB - Group 9 transition metal complexes have been widely explored as therapeutic
agents due to their unique geometry, their propensity to undergo ligand exchanges
with biomolecules and their diverse steric and electronic properties. These metal
complexes can offer distinct modes of action in living organisms compared to
carbon-based molecules. In this study, we investigated the antimicrobial and anti
proliferative abilities of a series of cyclometallated iridium(III) complexes.
The iridium(III) complex 1 inhibited the growth of S. aureus with MIC and MBC
values of 3.60 and 7.19 MUM, respectively, indicating its potent bactericidal
activity. Moreover, complex 1 also exhibited cytotoxicity against a number of
cancer cell lines, with particular potency against ovarian, cervical and melanoma
cells. This cyclometallated iridium(III) complex is the first example of a
substitutionally-inert, Group 9 organometallic compound utilized as a direct and
selective inhibitor of S. aureus.
PMID- 26416334
TI - The Incremental Effects of Manual Therapy or Booster Sessions in Addition to
Exercise Therapy for Knee Osteoarthritis: A Randomized Clinical Trial.
AB - STUDY DESIGN: A factorial randomized controlled trial. OBJECTIVES: To investigate
the addition of manual therapy to exercise therapy for the reduction of pain and
increase of physical function in people with knee osteoarthritis (OA), and
whether "booster sessions" compared to consecutive sessions may improve outcomes.
BACKGROUND: The benefits of providing manual therapy in addition to exercise
therapy, or of distributing treatment sessions over time using periodic booster
sessions, in people with knee OA are not well established. METHODS: All
participants had knee OA and were provided 12 sessions of multimodal exercise
therapy supervised by a physical therapist. Participants were randomly allocated
to 1 of 4 groups: exercise therapy in consecutive sessions, exercise therapy
distributed over a year using booster sessions, exercise therapy plus manual
therapy without booster sessions, and exercise therapy plus manual therapy with
booster sessions. The primary outcome measure was the Western Ontario and
McMaster Universities Osteoarthritis Index (WOMAC score; 0-240 scale) at 1-year
follow-up. Secondary outcome measures were the numeric pain-rating scale and
physical performance tests. RESULTS: Of 75 participants recruited, 66 (88%) were
retained at 1-year follow-up. Factorial analysis of covariance of the main
effects showed significant benefit from booster sessions (P = .009) and manual
therapy (P = .023) over exercise therapy alone. Group analysis showed that
exercise therapy with booster sessions (WOMAC score, -46.0 points; 95% confidence
interval [CI]: -80.0, -12.0) and exercise therapy plus manual therapy (WOMAC
score, -37.5 points; 95% CI: -69.7, -5.5) had superior effects compared with
exercise therapy alone. The combined strategy of exercise therapy plus manual
therapy with booster sessions was not superior to exercise therapy alone.
CONCLUSION: Distributing 12 sessions of exercise therapy over a year in the form
of booster sessions was more effective than providing 12 consecutive exercise
therapy sessions. Providing manual therapy in addition to exercise therapy
improved treatment effectiveness compared to providing 12 consecutive exercise
therapy sessions alone. Trial registered with the Australian New Zealand Clinical
Trials Registry (ACTRN12612000460808).
PMID- 26416335
TI - Mirror Symmetry Breaking by Chirality Synchronisation in Liquids and Liquid
Crystals of Achiral Molecules.
AB - Spontaneous mirror symmetry breaking is an efficient way to obtain homogeneously
chiral agents, pharmaceutical ingredients and materials. It is also in the focus
of the discussion around the emergence of uniform chirality in biological
systems. Tremendous progress has been made by symmetry breaking during
crystallisation from supercooled melts or supersaturates solutions and by self
assembly on solid surfaces and in other highly ordered structures. However,
recent observations of spontaneous mirror symmetry breaking in liquids and liquid
crystals indicate that it is not limited to the well-ordered solid state. Herein,
progress in the understanding of a new dynamic mode of symmetry breaking, based
on chirality synchronisation of transiently chiral molecules in isotropic liquids
and in bicontinuous cubic, columnar, smectic and nematic liquid crystalline
phases is discussed. This process leads to spontaneous deracemisation in the
liquid state under thermodynamic control, giving rise to long-term stable
symmetry-broken fluids, even at high temperatures. These fluids form
conglomerates that are capable of extraordinary strong chirality amplification,
eventually leading to homochirality and providing a new view on the discussion of
emergence of uniform chirality in prebiotic systems.
PMID- 26416336
TI - Site and mechanism of the colokinetic action of the ghrelin receptor agonist,
HM01.
AB - BACKGROUND: It has been recently demonstrated that the ghrelin receptor agonist,
HM01, caused defecation in rats that were treated to provide a model for the
constipation of Parkinson's disease. HM01 significantly increased fecal output
and increased Fos activity in neurons of the hypothalamus and hindbrain, but not
in the spinal defecation center. Other ghrelin agonists act on the defecation
center. METHODS: Receptor pharmacology was examined in ghrelin receptor (GHSR1a)
transfected cells. Anesthetized rats were used to investigate sites and
mechanisms of action. KEY RESULTS: HM01 activated rat GHSR1a at nanomolar
concentrations and was antagonized by the GHSR1a antagonist, YIL781. HM01,
intravenous, was potent to activate propulsive colorectal contractions. This was
prevented by pelvic nerve section and by intravenous YIL781, but not by spinal
cord section rostral to the defecation centers. Direct intrathecal application of
HM01 to the defecation center at spinal level L6-S1 initiated propulsive
contractions of the colorectum. CONCLUSIONS & INFERENCES: HM01 stimulates GHSR1a
receptors on neurons in the lumbosacral defecation centers to cause propulsive
contractions and emptying of the colorectum. It has greater potency when given
systemically, compared with other GHSR1a agonists.
PMID- 26416337
TI - Simultaneous Determination of Naturally Occurring Estrogens and Mycoestrogens in
Milk by Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry
Analysis.
AB - A simple, fast, and reproducible method for the simultaneous determination of
natural estrogens and mycoestrogens (resorcylic acid lactones) in milk by
ultrahigh-performance liquid chromatography combined with electrospray ionization
triple quadrupole tandem mass spectrometry (UHPLC/ESI-MS/MS) is described. The
extraction was carried out by solid-phase extraction (SPE) using graphitized
carbon black as solid sorbent. The use of carbon black allowed us to avoid any
type of sample pretreatment, and the extraction was performed simply by diluting
milk samples in water. Correlation coefficient values were obtained in the range
between 0.9991 and 1, with good recoveries (67-107% at the lowest spiked level),
repeatability (4.8-16.8%), and reproducibility (3.2-16.3%). Moreover, a very low
matrix effect was observed for both estrogens and mycoestrogens. With respect to
a previous method based on SPE with Oasis MAX cartridges, the one here described
allowed us to detect all the analytes under investigation, at the lowest tested
concentration level, including free estrogens (in particular estriol). Finally,
the developed UHPLC/ESI-MS/MS method was applied to the analysis of some whole
milk samples from different lactating animals (cow, goat, and donkey) as well as
ultrahigh-temperature-treated cow milk and powder milk samples.
PMID- 26416338
TI - Gut microbiota: The gut virome and bacterial microbiome-the early years.
PMID- 26416339
TI - Epidemiology and Characteristics of Episodic Breathlessness in Advanced Cancer
Patients: An Observational Study.
AB - CONTEXT: Episodic breathlessness is a relevant aspect in patients with advanced
cancer. OBJECTIVES: The aim of this study was to assess the different aspects of
this clinical phenomenon. METHODS: A consecutive sample of patients with advanced
cancer admitted to different settings for a period of six months was surveyed.
The presence of background breathlessness and episodic breathlessness, their
intensity (numerical scale 0-10), and drugs used for treatment were collected.
Factors inducing episodic breathlessness and its influence on daily activities
were investigated. RESULTS: Of 921 patients, 29.3% (n = 269) had breathlessness
and 134 patients (49.8%) were receiving drugs for background breathlessness. In
the multivariate analysis, the risk of breathlessness increased with chronic
obstructive pulmonary disease, although it decreased in patients receiving
disease-oriented therapy and patients with gastrointestinal tumors. The
prevalence of episodic breathlessness was 70.9% (n = 188), and its mean intensity
was 7.1 (SD 1.6). The mean duration of untreated episodic breathlessness was 19.9
minutes (SD 35.3); 41% of these patients were receiving drugs for episodic
breathlessness. The majority of episodic breathlessness events (88.2%) were
triggered by activity. In the multivariate analysis, higher Karnofsky Performance
Status levels were significantly related to episodic breathlessness, although
patients receiving disease-oriented therapy were less likely to have episodic
breathlessness. CONCLUSION: This study showed that episodic breathlessness
frequently occurs in patients with breathlessness in the advanced stage of
disease, has a severe intensity, and is characterized by rapid onset and short
duration, which require rapid measures.
PMID- 26416340
TI - Sitting Time, Fidgeting, and All-Cause Mortality in the UK Women's Cohort Study.
AB - INTRODUCTION: Sedentary behaviors (including sitting) may increase mortality risk
independently of physical activity level. Little is known about how fidgeting
behaviors might modify the association. METHODS: Data were from the United
Kingdom (UK) Women's Cohort Study. In 1999-2002, a total of 12,778 women (aged 37
78 years) provided data on average daily sitting time, overall fidgeting
(irrespective of posture), and a range of relevant covariates including physical
activity, diet, smoking status, and alcohol consumption. Participants were
followed for mortality over a mean of 12 years. Proportional hazards Cox
regression models estimated the relative risk of mortality in high (versus low)
and medium (versus low) sitting time groups. RESULTS: Fidgeting modified the risk
associated with sitting time (p=0.04 for interaction), leading us to separate
groups for analysis. Adjusting for covariates, sitting for >=7 hours/day (versus
<5 hours/day) was associated with 30% increased all-cause mortality risk (hazard
ratio [HR]=1.30, 95% CI=1.02, 1.66) only among women in the low fidgeting group.
Among women in the high fidgeting group, sitting for 5-6 hours/day (versus <5
hours/day) was associated with decreased mortality risk (HR=0.63, 95% CI=0.43,
0.91), adjusting for a range of covariates. There was no increased mortality risk
from longer sitting time in the middle and high fidgeting groups. CONCLUSIONS:
Fidgeting may reduce the risk of all-cause mortality associated with excessive
sitting time. More detailed and better-validated measures of fidgeting should be
identified in other studies to replicate these findings and identity mechanisms,
particularly measures that distinguish fidgeting in a seated from standing
posture.
PMID- 26416341
TI - Epidemiology and costs of patients with toxic epidermal necrolysis: a 27-year
retrospective study.
AB - BACKGROUND: Recently, the importance of reporting the results and principles of
management in Toxic epidermal necrolysis (TEN) patients was underscored.
Treatment of TEN focuses on supportive care, often provided in a burn centre
setting. Mortality in TEN patients can be high; the SCORTEN score is a scoring
system that predicts mortality in patients with TEN. The predictive value of the
SCORTEN score in our setting is unclear, as are the treatment costs of TEN
patients. OBJECTIVE: To describe patient characteristics, treatment, outcome and
direct medical costs of patients with TEN treated in one Dutch burn centre in a
27-year period. In addition, determinants of mortality and the predictive value
of the SCORTEN score were assessed. METHODS: A retrospective study was conducted
in all patients with TEN (including Stevens-Johnson syndrome (SJS) and overlap
SJS-TEN) admitted to the burn centre Rotterdam between January 1987 and December
2013. The discriminative value of the SCORTEN score was assessed by receiver
operator characteristics curve analysis. RESULTS: A total of 63 patients were
admitted in 27-year period. Overall mortality was 39.7%, mortality in TEN
patients (>30%TBSA) was 37.1%. A higher age (OR = 1.04, 95%CI: 1.02-1.07) and
comorbidity (OR = 4.25, 95%CI: 1.2-14.7) were associated with mortality. The
discriminative value of the SCORTEN prediction model in our population was
limited (AUC=0.72, 95%CI: 0.57-0.86). The mean direct medical hospital-based
costs was ?41.361. CONCLUSION: Toxic epidermal necrolysis is a severe adverse
drug reaction, with a high mortality. Elderly patients and patients with
comorbidity, especially circulatory comorbidity, have a relatively high risk of
decease. The SCORTEN score, a frequently used prediction model in patients with
TEN, underestimated the mortality in our study, mainly due to limited
availability in patients with a good prognosis. The treatment of patient with TEN
is associated with high direct medical hospital-based costs, also compared to
burn patients in general.
PMID- 26416342
TI - NbRABG3f, a member of Rab GTPase, is involved in Bamboo mosaic virus infection in
Nicotiana benthamiana.
AB - The screening of differentially expressed genes in plants after pathogen
infection can uncover the potential host factors required for the pathogens. In
this study, an up-regulated gene was identified and cloned from Nicotiana
benthamiana plants after Bamboo mosaic virus (BaMV) inoculation. The up-regulated
gene was identified as a member of the Rab small guanosine triphosphatase
(GTPase) family, and was designated as NbRABG3f according to its in silico
translated product with high identity to that of RABG3f of tomato. Knocking down
the expression of NbRABG3f using a virus-induced gene silencing technique in a
protoplast inoculation assay significantly reduced the accumulation of BaMV. A
transiently expressed NbRABG3f protein in N. benthamiana plants followed by BaMV
inoculation enhanced the accumulation of BaMV to approximately 150%. Mutants that
had the catalytic site mutation (NbRABG3f/T22N) or had lost their membrane
targeting capability (NbRABG3f/DeltaC3) failed to facilitate the accumulation of
BaMV in plants. Because the Rab GTPase is responsible for vesicle trafficking
between organelles, a mutant with a fixed guanosine diphosphate form was used to
identify the donor compartment. The use of green fluorescent protein (GFP) fusion
revealed that GFP-NbRABG3f/T22N clearly co-localized with the Golgi marker. In
conclusion, BaMV may use NbRABG3f to form vesicles derived from the Golgi
membrane for intracellular trafficking to deliver unidentified factors to its
replication site; thus, both GTPase activity and membrane-targeting ability are
crucial for BaMV accumulation at the cell level.
PMID- 26416343
TI - The Effects of Job Insecurity on Health Care Utilization: Findings from a Panel
of U.S. Workers.
AB - OBJECTIVE: To examine the impacts of job insecurity during the recession of 2007
2009 on health care utilization among a panel of U.S. employees. DATA
SOURCES/STUDY SETTING: Linked administrative and claims datasets on a panel of
continuously employed, continuously insured individuals at a large multisite
manufacturing firm that experienced widespread layoffs (N = 9,486). STUDY DESIGN:
We employed segmented regressions to examine temporal discontinuities in
utilization during 2006-2012. To assess the effects of job insecurity, we
compared individuals at high- and low-layoff plants. Because the dataset includes
multiple observations for each individual, we included individual-level fixed
effects. PRINCIPAL FINDINGS: We found discontinuous increases in outpatient (3.5
visits/month/10,000 individuals, p = .002) and emergency (0.4 visits/month/10,000
individuals, p = .05) utilization in the panel of all employees. Compared with
individuals at low-layoff plants, individuals at high-layoff plants decreased
outpatient utilization (-4.0 visits/month/10,000 individuals, p = .008),
suggesting foregone preventive care, with a marginally significant increase in
emergency utilization (0.4 visits/month/10,000 individuals, p = .08).
CONCLUSIONS: These results suggest changes in health care utilization and
potentially adverse impacts on employee health in response to job insecurity
during the latest recession. This study contributes to our understanding of the
impacts of economic crises on the health of the U.S. working population.
PMID- 26416344
TI - An evidence-based review of systemic treatments for itch.
AB - BACKGROUND AND OBJECTIVE: Many treatment modalities are used for itch treatment
in daily medical practices without adequate evidence of their efficacy. The
purpose of this study was to provide an evidence-based review of the literature
as to the clinical benefits of systemic anti-itch treatments. DATABASES AND DATA
TREATMENT: We performed a systematic review and, when appropriate, meta-analysis
from available placebo-controlled randomized controlled trails (RCTs). A
systematic search of the literature was performed using Pub Med, Cochrane Library
and EMBASE. The primary outcome was the change in the itch score comparing the
intervention group and placebo group. The meta-analysis method was used to
calculate the pooled outcome of each treatment modality. RESULTS: Twenty-six
eligible RCTs were included. We found evidence for the effectiveness of:
naltrexone (in cholestatic itch and atopic eczema), nalfurafine (in uraemic
itch), gabapentin (in uraemic itch) and ursodeoxycholic acid (in intrahepatic
cholestasis of pregnancy). The results of two RCTs with naltrexone in uremic itch
are conflicting. On the other hand, we did not find any benefit from ondansetron
(in cholestatic and uraemic itch), ergocalciferol (in uraemic itch), colesevelam
(in cholestatic itch) or gabapentin (in cholestatic itch). The possible
effectiveness of sertraline, paroxetine, cromolyn sodium, zinc sulphate, omega-3
fatty acid, montelukast, doxepin and rifampin need to be confirmed from future
large studies, because the available evidence is insufficient. CONCLUSIONS: The
findings from this study suggest the effective therapeutic approaches for itch.
The major limitations are that there are small numbers of available RCTs and
methodological differences across studies.
PMID- 26416345
TI - Smoking affects the oral glucose tolerance test profile and the relationship
between glucose and HbA1c in gestational diabetes mellitus.
AB - AIMS: Current smokers in the general population have a lower 2 h plasma glucose
after an oral glucose tolerance test (OGTT) and a higher HbA1c than non-smokers,
but the relationships between OGTT/HbA1c and smoking status have not been
addressed in pregnancy. We analysed glycaemic measurements in women with
gestational diabetes mellitus in relation to smoking status. METHODS: We
performed a review of the prospectively collected database of the diabetes and
pregnancy clinic. We included women with gestational diabetes mellitus and a
singleton pregnancy who delivered between 1986 and 2006. Bivariate and
multivariate analyses were used to evaluate patient characteristics in relation
to smoking status. RESULTS: A total of 2361 women met the inclusion criteria: 556
(23.5%) were active smokers, 266 (11.3%) quit during pregnancy and 1539 (65.2%)
were non-smokers. Most baseline characteristics were similar across groups.
Diagnostic OGTT was performed at a gestational age of [median (25th, 75(th)
centiles)] 29 weeks (26, 33). Women who smoked at the beginning of pregnancy had
a higher 1-h plasma glucose than non-smokers [11.8 (11, 12.7), 11.6 (11, 12.6)
and 11.5 (10.8, 12.5) mmol/l, for active smokers, those who quit during pregnancy
and non-smokers, respectively, P < 0.001] and a lower 3-h plasma glucose [7.3
(5.9, 8.4), 7.6 (6.4, 8.7) and 8.0 (6.8, 9.0) mmol/l, respectively, P < 0.001].
HbA1c was higher in women who smoked at the beginning of pregnancy. Multiple
regression analysis confirmed the independent association of smoking status with
HbA1c and OGTT plasma glucose. CONCLUSIONS: In women with gestational diabetes
mellitus who smoke at the beginning of pregnancy, the shape of the OGTT is
consistent with accelerated glucose absorption, and HbA1c is higher than expected
for glycaemic values.
PMID- 26416346
TI - In vitro expression of cytokeratin 18, 19 and tube formation of adipose-derived
stem cells induced by the breast epithelial cell line HBL-100.
AB - Fat transplantation is increasingly used in breast augmentation; and recently,
the issue of safety concerns from a cellular and molecular point of view has been
raised. In this study, attentions were paid to the interaction between adipose
derived stem cells (ADSC) and mammary epithelial cells: human breast cancer cell
line - 100 (HBL - 100) cells were used to simulate the normal microenvironment in
breast tissue, ADSCs were harvest from human and co-cultured with HBL-100 cells.
It was found that ADSCs formed tube-like structures in the co-culture with HBL
100 cells in contrast to the normal morphology of ADSCs in the control group. In
addition, the immunofluorescence imaging showed that cytokeratin 18 and 19 (CK18
and 19) were significantly expressed in ADSCs after the co-culture with HBL-100
cells. The ultrastructure of those ADSCs also showed epithelial changes. In
conclusion, ADSCs are not biological stable when co-cultured with HBL-100 cells.
They differentiate into epithelial-like cells with the expression of epithelial
surface marks (CK 18, 19) and form tube-like structures. This may offer an
important evidence for the further study of clinical application of transplanting
ADSCs rich adipose tissue into the breast in the future.
PMID- 26416348
TI - Pharmacokinetics of ketorolac tromethamine in horses after intravenous,
intramuscular, and oral single-dose administration.
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral component of equine
analgesia, yet currently available NSAIDs are both limited in their analgesic
efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is
widely used in humans as a potent morphine-sparing analgesic drug but has not
been fully evaluated in horses. The purpose of this study was to determine the
pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular
(i.m.), and oral (p.o.) administration. Nine healthy adult horses received a
single 0.5-mg/kg dose of KT via each route of administration. Plasma was
collected up to 48 h postadministration and analyzed for KT concentration using
HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma
clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at
steady-state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o.
dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The
drug was rapidly absorbed after i.m. and p.o. administration, and mean
bioavailability was 71% and 57% for i.m. and p.o. administration, respectively.
Adverse effects were not observed after i.v., i.m., and p.o. administration. More
studies are needed to evaluate the analgesic and anti-inflammatory properties of
KT in horses.
PMID- 26416349
TI - Raman spectroscopy as probe of nanometre-scale strain variations in graphene.
AB - Confocal Raman spectroscopy has emerged as a major, versatile workhorse for the
non-invasive characterization of graphene. Although it is successfully used to
determine the number of layers, the quality of edges, and the effects of strain,
doping and disorder, the nature of the experimentally observed broadening of the
most prominent Raman 2D line has remained unclear. Here we show that the observed
2D line width contains valuable information on strain variations in graphene on
length scales far below the laser spot size, that is, on the nanometre-scale.
This finding is highly relevant as it has been shown recently that such nanometre
scaled strain variations limit the carrier mobility in high-quality graphene
devices. Consequently, the 2D line width is a good and easily accessible quantity
for classifying the crystalline quality, nanometre-scale flatness as well as
local electronic properties of graphene, all important for future scientific and
industrial applications.
PMID- 26416350
TI - The Effects of Platelet-Rich Plasma on Cell Proliferation and Adipogenic
Potential of Adipose-Derived Stem Cells.
AB - BACKGROUND: Platelet-rich plasma (PRP) contains multiple growth factors and has
been shown to enhance fat graft survival after lipotransfer. However, the
molecular mechanisms mediating this effect remain unknown. Adipose-derived stem
cells (ASCs) play an important role in fat graft survival and are a likely target
for PRP-mediated effects. This study seeks to investigate the impact of PRP on
ASC proliferation and adipogenic differentiation. METHODS: Human ASCs were
isolated using our laboratory protocol. The experiments were divided into four
arms: (1) ASCs cultured in general culture medium alone; (2) ASCs in general
culture medium + 5%, 10%, 15%, or 20% PRP; (3) ASCs cultured in adipogenic
differentiation medium alone; (4) ASCs cultured in adipogenic medium + 5%, 10%,
15%, or 20% PRP. Cell proliferation was analyzed and comparative m-RNA expression
of adipogenic genes was assessed by quantitative PCR. Protein expression was
determined by western blot. RESULTS: PRP significantly enhanced proliferation of
ASCs, even in the presence of antiproliferative, proadipogenic media. In
contrast, PRP inhibited adipogenic differentiation in adipogenic media, evidenced
by decreased intracellular lipid accumulation and reduced adipogenic gene
expression (PPAR-gamma and FABP4). Inhibition appears to occur through
downregulation of bone morphogenetic protein receptor IA (BMPRIA) and fibroblast
growth factor receptor 1 (FGFR1). Interestingly, PRP elicited these effects
across the entire range of doses studied. CONCLUSIONS: PRP appears to modulate
ASC function primarily by enhancing cell proliferation. The consequences of its
impact on adipogenesis are less clear. Enhanced proliferation initially might set
the stage for more robust regeneration and adipogenesis at later time points,
providing an important target for ongoing research.
PMID- 26416351
TI - Pharmacological inhibition of Bcl-xL sensitizes osteosarcoma to doxorubicin.
AB - High-grade conventional osteosarcoma is the most common primary bone tumor.
Prognosis for osteosarcoma patients is poor and resistance to chemotherapy is
common. We performed an siRNA screen targeting members of the Bcl-2 family in
human osteosarcoma cell lines to identify critical regulators of osteosarcoma
cell survival. Silencing the anti-apoptotic family member Bcl-xL but also the pro
apoptotic member Bak using a SMARTpool of siRNAs as well as 4/4 individual siRNAs
caused loss of viability. Loss of Bak impaired cell cycle progression and
triggered autophagy. Instead, silencing Bcl-xL induced apoptotic cell death. Bcl
xL was expressed in clinical osteosarcoma samples but mRNA or protein levels did
not significantly correlate with therapy response or survival. Nevertheless,
pharmacological inhibition of a range of Bcl-2 family members showed that
inhibitors targeting Bcl-xL synergistically enhanced the response to the
chemotherapeutic agent, doxorubicin. Indeed, in osteosarcoma cells strongly
expressing Bcl-xL, the Bcl-xL-selective BH3 mimetic, WEHI-539 potently enhanced
apoptosis in the presence of low doses of doxorubicin. Our results identify Bcl
xL as a candidate drug target for sensitization to chemotherapy in patients with
osteosarcoma.
PMID- 26416352
TI - The chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary
metastasis via ADCC and CDC rather than via its neutralizing activity.
AB - Podoplanin (PDPN/Aggrus/T1alpha) binds to C-type lectin-like receptor-2 (CLEC-2)
and induces platelet aggregation. PDPN is associated with malignant progression,
tumor metastasis, and poor prognosis in several types of cancer. Although many
anti-human PDPN (hPDPN) monoclonal antibodies (mAbs), such as D2-40 and NZ-1,
have been established, these epitopes are limited to the platelet aggregation
stimulating (PLAG) domain (amino acids 29-54) of hPDPN. Recently, we developed a
novel mouse anti-hPDPN mAb, LpMab-7, which is more sensitive than D2-40 and NZ-1,
using the Cancer-specific mAb (CasMab) method. The epitope of LpMab-7 was shown
to be entirely different from that of NZ-1, a neutralizing mAb against the PLAG
domain according to an inhibition assay and lectin microarray analysis. In the
present study, we produced a mouse-human chimeric anti-hPDPN mAb, chLpMab-7.
ChLpMab-7 showed high antibody-dependent cellular cytotoxicity (ADCC) and
complement-dependent cytotoxicity (CDC). Furthermore, chLpMab-7 inhibited the
growth of hPDPN-expressing tumors in vivo. Although chLpMab-7 recognizes a non
PLAG domain of hPDPN, it suppressed the hematogenous metastasis of hPDPN
expressing tumors. These results indicated that chLpMab-7 suppressed tumor
development and hematogenous metastasis in a neutralization-independent manner.
In conclusion, hPDPN shows promise as a target in the development of a novel
antibody-based therapy.
PMID- 26416353
TI - Methionine adenosyltransferase alpha2 sumoylation positively regulate Bcl-2
expression in human colon and liver cancer cells.
AB - Ubiquitin-conjugating enzyme 9 (Ubc9) is required for sumoylation and inhibits
apoptosis via Bcl-2 by unknown mechanism. Methionine adenosyltransferase 2A
(MAT2A) encodes for MATalpha2, the catalytic subunit of the MATII isoenzyme that
synthesizes S-adenosylmethionine (SAMe). Ubc9, Bcl-2 and MAT2A expression are up
regulated in several malignancies. Exogenous SAMe decreases Ubc9 and MAT2A
expression and is pro-apoptotic in liver and colon cancer cells. Here we
investigated whether there is interplay between Ubc9, MAT2A and Bcl-2. We used
human colon and liver cancer cell lines RKO and HepG2, respectively, and
confirmed key finding in colon cancer specimens. We found MATalpha2 can regulate
Bcl-2 expression at multiple levels. MATalpha2 binds to Bcl-2 promoter to
activate its transcription. This effect is independent of SAMe as MATalpha2
catalytic mutant was also effective. MATalpha2 also directly interacts with Bcl-2
to enhance its protein stability. MATalpha2's effect on Bcl-2 requires Ubc9 as
MATalpha2's stability is influenced by sumoylation at K340, K372 and K394.
Overexpressing wild type (but not less stable MATalpha2 sumoylation mutants)
protected from 5-fluorouracil-induced apoptosis in both colon and liver cancer
cells. Colon cancer have higher levels of sumoylated MATalpha2, total MATalpha2,
Ubc9 and Bcl-2 and higher MATalpha2 binding to the Bcl-2 P2 promoter. Taken
together, Ubc9's protective effect on apoptosis may be mediated at least in part
by sumoylating and stabilizing MATalpha2 protein, which in turn positively
maintains Bcl-2 expression. These interactions feed forward to further enhance
growth and survival of the cancer cell.
PMID- 26416356
TI - Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat.
AB - Erythropoietin (EPO) plays a critical role in the development of the nervous
system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity
were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses
of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic
protein (GFAP) levels in the serum were determined and water content of brain and
the extravasation of a tracer (Evans blue) were measured. Brain lipid
peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2
protein relative expressions were determined. Cation exchange chromatography was
used to evaluate MBP alterations. Seven days after exposure, pathological
assessment was performed after Kluver-Barrera staining. EPO reduced
malondialdehyde levels at all doses (2500, 5000 and 10,000 u/kg). Lower doses of
EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of
GFAP. EPO could not reduce the water content of the edematous poisoned brains.
However, at 5000 and 10,000 u/kg it protected the blood brain barrier against
integrity loss as a result of CO. EPO could significantly decrease the MPO
activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO
could partially prevent these biochemical changes. Fewer vacuoles and
demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could
restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced
it 38.86%. These results reveal that EPO could relatively prevent different
pathways of neurotoxicity by CO poisoning and thus has the potential to be used
as a novel approach to manage this poisoning.
PMID- 26416355
TI - Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal
phenotype in benign and cancer cells.
AB - Plasticity of cancer cells, manifested by transitions between epithelial and
mesenchymal phenotypes, represents a challenging issue in the treatment of
neoplasias. Both epithelial-mesenchymal transition (EMT) and mesenchymal
epithelial transition (MET) are implicated in the processes of metastasis
formation and acquisition of stem cell-like properties. Mouse double minute (MDM)
2 and MDMX are important players in cancer progression, as they act as regulators
of p53, but their function in EMT and metastasis may be contradictory. Here, we
show that the EMT phenotype in multiple cellular models and in clinical prostate
and breast cancer samples is associated with a decrease in MDM2 and increase in
MDMX expression. Modulation of EMT-accompanying changes in MDM2 expression in
benign and transformed prostate epithelial cells influences their migration
capacity and sensitivity to docetaxel. Analysis of putative mechanisms of MDM2
expression control demonstrates that in the context of defective p53 function,
MDM2 expression is regulated by EMT-inducing transcription factors Slug and
Twist. These results provide an alternative context-specific role of MDM2 in EMT,
cell migration, metastasis, and therapy resistance.
PMID- 26416354
TI - Sensitization of multidrug-resistant human cancer cells to Hsp90 inhibitors by
down-regulation of SIRT1.
AB - The effectiveness of Hsp90 inhibitors as anticancer agents was limited in
multidrug-resistant (MDR) human cancer cells due to induction of heat shock
proteins (Hsps) such as Hsp70/Hsp27 and P-glycoprotein (P-gp)-mediated efflux. In
the present study, we showed that resistance to Hsp90 inhibitors of MDR human
cancer cells could be overcome with SIRT1 inhibition. SIRT1 knock-down or SIRT1
inhibitors (amurensin G and EX527) effectively suppressed the resistance to Hsp90
inhibitors (17-AAG and AUY922) in several MDR variants of human lymphoblastic
leukemia and human breast cancer cell lines. SIRT1 inhibition down-regulated the
expression of heat shock factor 1 (HSF1) and subsequently Hsps and facilitated
Hsp90 multichaperone complex disruption via hyperacetylation of Hsp90/Hsp70.
These findings were followed by acceleration of ubiquitin ligase CHIP-mediated
mutant p53 (mut p53) degradation and subsequent down-regulation of P-gp in 17-AAG
treated MDR cancer cells expressing P-gp and mut p53 after inhibition of SIRT1.
Therefore, combined treatment with Hsp90 inhibitor and SIRT1 inhibitor could be a
more effective therapeutic approach for Hsp90 inhibitor-resistant MDR cells via
down-regulation of HSF1/Hsps, mut p53 and P-gp.
PMID- 26416357
TI - Identification, sequencing and comparative analysis of pBp15.S plasmid from the
newly described entomopathogen Bacillus pumilus 15.1.
AB - The Bacillus pumilus 15.1 strain, a recently described entomopathogenic strain
active against Ceratitis capitata, contains at least two extrachromosomal
elements, pBp15.1S and pBp15.1B. Given that B. pumilus is not a typical
entomopathogenic bacterium, the acquisition of this extrachromosomal DNA may
explain why B. pumilus 15.1 is toxic to an insect. One of the plasmids present in
the strain, the pBp15.1S plasmid, was sub-cloned, sequenced and analyzed using
bioinformatics to identify any potential virulence factor. The pBp15.1S plasmid
was found to be 7785 bp in size with a GC content of 35.7% and 11 putative ORFs.
A replication module typical of a small rolling circle plasmid and a sensing and
regulatory system specific for plasmids was found in pBp15.1S. Additionally, we
demonstrated the existence of ssDNA in plasmid preparations suggesting that
pBp15.1S replicates by the small rolling circle mechanism. A gene cluster present
in plasmid pPZZ84 from a distantly isolated B. pumilus strain was also present in
pBp15.1S. The plasmid copy number of pBp15.1S in exponentially growing B. pumilus
cells was determined to be 33 copies per chromosome. After an extensive plasmid
characterization, no known virulence factor was found so a search in the other
extrachromosomal elements of the bacteria is needed.
PMID- 26416358
TI - Co(OH)2/RGO/NiO sandwich-structured nanotube arrays with special surface and
synergistic effects as high-performance positive electrodes for asymmetric
supercapacitors.
AB - High power density, high energy density and excellent cycling stability are the
main requirements for high-performance supercapacitors (SCs) that will be widely
used for portable consumer electronics and hybrid electric vehicles. Here we
investigate novel types of hybrid Co(OH)2/reduced graphene oxide (RGO)/NiO
sandwich-structured nanotube arrays (SNTAs) as positive electrodes for asymmetric
supercapacitors (ASCs). The synthesized Co(OH)2/RGO/NiO SNTAs exhibit a
significantly improved specific capacity (~1470 F g(-1) at 5 mV s(-1)) and
excellent cycling stability with ~98% Csp retention after 10 000 cycles because
of the fast transport and short diffusion paths for electroactive species, the
high utilization rate of electrode materials, and special synergistic effects
among Co(OH)2, RGO, and NiO. The high-performance ASCs are assembled using
Co(OH)2/RGO/NiO SNTAs as positive electrodes and active carbon (AC) as negative
electrodes, and they exhibit a high energy density (115 Wh kg(-1)), a high power
density (27.5 kW kg(-1)) and an excellent cycling stability (less 5% Csp loss
after 10 000 cycles). This study shows an important breakthrough in the design
and fabrication of multi-walled hybrid nanotube arrays as positive electrodes for
ASCs.
PMID- 26416359
TI - Shape Displays: Spatial Interaction with Dynamic Physical Form.
AB - Shape displays are an emerging class of devices that emphasize actuation to
enable rich physical interaction, complementing concepts in virtual and augmented
reality. The ability to render form introduces new opportunities to touch, grasp,
and manipulate dynamic physical content and tangible objects, in both nearby and
remote environments. This article presents novel hardware, interaction
techniques, and applications, which point to the potential for extending the ways
that we traditionally interact with the physical world, empowered by digital
computation.
PMID- 26416360
TI - Reducing Visual Discomfort with HMDs Using Dynamic Depth of Field.
AB - Although head-mounted displays (HMDs) are ideal devices for personal viewing of
immersive stereoscopic content, exposure to VR applications on them results in
significant discomfort for the majority of people, with symptoms including eye
fatigue, headaches, nausea, and sweating. A conflict between accommodation and
vergence depth cues on stereoscopic displays is a significant cause of visual
discomfort. This article describes the results of an evaluation used to judge the
effectiveness of dynamic depth-of-field (DoF) blur in an effort to reduce
discomfort caused by exposure to stereoscopic content on HMDs. Using a commercial
game engine implementation, study participants report a reduction of visual
discomfort on a simulator sickness questionnaire when DoF blurring is enabled.
The study participants reported a decrease in symptom severity caused by HMD
exposure, indicating that dynamic DoF can effectively reduce visual discomfort.
PMID- 26416361
TI - Sensing Thumb-to-Finger Taps for Symbolic Input in VR/AR Environments.
AB - Thumb-to-finger tap interaction can be employed to perform eyes-free, discrete,
symbolic input in virtual and augmented reality environments. The DigiTap device
is worn on the wrist to keep the hand free from any instrumentation so as not to
impair tactile sense and dexterity. DigiTap senses the jerk that is caused by a
tap and takes an image sequence to detect the tap location. The device can
recognize taps at 12 different locations on the fingers, and at some positions,
it can even distinguish between different tap strengths. The authors conducted an
extended user study to evaluate users' abilities to interact with the device and
perform symbolic input.
PMID- 26416362
TI - Visual Perspective and Feedback Guidance for VR Free-Throw Training.
AB - Accurate distance perception and natural interactions are mandatory conditions
when training precision aiming tasks in VR. However, many factors specific to
virtual environments (VEs) lead to differences in the way users execute a motor
task in VR versus the real world. To investigate these differences, the authors
performed a study on basketball beginners' free-throw performance in VEs under
different visual conditions. Although the success rate is not statistically
different, some adaptations occurred in the way the users performed the task,
depending on the visual conditions. In the third-person perspective visual
condition, the release parameters indicate that the users more accurately
estimated distance to target. Adding visual guidance information (gradual depth
information showing the ideal ball trajectory) also led to more natural motor
behavior. The final aim of this study was to develop a reliable basketball free
throw training system in VEs, so the authors compared beginners' performances in
VR with experts' models of performance. Their results show that most of the
performance variables tended to evolve closer to the experts' performance during
the training in the VE.
PMID- 26416363
TI - Toward Standard Usability Questionnaires for Handheld Augmented Reality.
AB - Usability evaluations are important to improving handheld augmented reality (HAR)
systems. However, no standard questionnaire considers perceptual and ergonomic
issues found in HAR. The authors performed a systematic literature review to
enumerate these issues. Based on these issues, they created a HAR usability scale
that consists of comprehensibility and manipulability scales. These scales
measure general system usability, ease of understanding the information
presented, and ease of handling the device. The questionnaires' validity and
reliability were evaluated in four experiments, and the results show that the
questionnaires consistently correlate with other subjective and objective
measures of usability. The questionnaires also have good reliability based on the
Cronbach's alpha. Researchers and professionals can directly use these
questionnaires to evaluate their own HAR applications or modify them with the
insights presented in this article.
PMID- 26416364
TI - Contiguous Animated Edge-Based Cartograms for Traffic Visualization.
AB - An experimental model animates contiguous computer cartograms by distorting the
topological lengths of their edges. Using traffic information for the city of
Lisbon, the authors distort a road map to depict traffic velocities. Areas of the
city distend when velocities are low and compress when velocities are high. This
model is applied to two visualizations: a trajectory visualization of vehicles,
creating a temperature map for traffic velocities, and a figurative visualization
that portrays Lisbon as a system of pulsing blood vessels. The proposed model can
efficiently generate and animate edge-based cartograms with low representation
errors.
PMID- 26416365
TI - More Than Telling a Story: Transforming Data into Visually Shared Stories.
AB - The authors take a closer look at how the visualization community has discussed
visual storytelling and present a visual data storytelling process, incorporating
steps involved in finding insights (explore data), turning these insights into a
narrative (make a story), and communicating this narrative to an audience (tell a
story). They also discuss opportunities for future research in visualization as a
storytelling medium in the light of this broader process.
PMID- 26416366
TI - Breathing Life into Shapes.
AB - Shape articulation transforms a lifeless geometric object into a vibrant
character. Computers enrich artists' toolsets dramatically. They not only endow
artists with the power to manipulate virtual 2D and 3D scenes, but they also
eliminate tedium and expedite prototyping, freeing artists to focus on creative
aspects. With such power comes a temptation to lean entirely on the computer.
Computationally intensive animation systems sacrifice real-time feedback for
physical accuracy. How can we leverage modern computational power to create the
best possible shape deformations while maintaining real-time performance as a
mandatory invariant? This article summarizes efforts to answer this, culminating
in a deformation system with the quality of slow, nonlinear optimization, but at
lightning speed.
PMID- 26416367
TI - Evaluating and Grading Students in Large-Scale Image Processing Courses.
AB - In undergraduate practical courses, it is common to work with groups of 100 or
more students. These large-scale courses bring their own challenges. For example,
course problems are too small and lack "the big picture"; grading becomes
burdensome and repetitive for the teaching staff; and it is difficult to detect
cheating. Based on their experience with a traditional large-scale practical
course in image processing, the authors developed a novel course approach to
teaching "Introduction to Digital Image Processing" (or EDBV, from the German
course title Einfuhrung in die Digitale Bild-Verarbeitung) for all undergraduate
students of media informatics and visual computing and medical informatics at the
TU Wien.
PMID- 26416368
TI - Evidence based policy making and the 'art' of commissioning - how English
healthcare commissioners access and use information and academic research in
'real life' decision-making: an empirical qualitative study.
AB - BACKGROUND: Policymakers such as English healthcare commissioners are encouraged
to adopt 'evidence-based policy-making', with 'evidence' defined by researchers
as academic research. To learn how academic research can influence policy,
researchers need to know more about commissioning, commissioners' information
seeking behaviour and the role of research in their decisions. METHODS: In case
studies of four commissioning organisations, we interviewed 52 people including
clinical and managerial commissioners, observed 14 commissioning meetings and
collected documentation e.g. meeting minutes and reports. Using constant
comparison, data were coded, summarised and analysed to facilitate cross case
comparison. RESULTS: The 'art of commissioning' entails juggling competing
agendas, priorities, power relationships, demands and personal inclinations to
build a persuasive, compelling case. Policymakers sought information to identify
options, navigate ways through, justify decisions and convince others to approve
and/or follow the suggested course. 'Evidence-based policy-making' usually meant
pragmatic selection of 'evidence' such as best practice guidance, clinicians' and
users' views of services and innovations from elsewhere. Inconclusive or negative
research was unhelpful in developing policymaking plans and did not inform
disinvestment decisions. Information was exchanged through conversations and
stories, which were fast, flexible and suited the rapidly changing world of
policymaking. Local data often trumped national or research-based evidence. Local
evaluations were more useful than academic research. DISCUSSION: Commissioners
are highly pragmatic and will only use information that helps them create a
compelling case for action.Therefore, researchers need to start producing more
useful information. CONCLUSIONS: To influence policymakers' decisions,
researchers need to 1) learn more about local policymakers' priorities 2) develop
relationships of mutual benefit 3) use verbal instead of writtencommunication 4)
work with intermediaries such as public health consultants and 5) co-produce
local evaluations.
PMID- 26416369
TI - Validity, reliability and support for implementation of independence-scaled
procedural assessment in laparoscopic surgery.
AB - BACKGROUND: There is no widely used method to evaluate procedure-specific
laparoscopic skills. The first aim of this study was to develop a procedure-based
assessment method. The second aim was to compare its validity, reliability and
feasibility with currently available global rating scales (GRSs). METHODS: An
independence-scaled procedural assessment was created by linking the procedural
key steps of the laparoscopic cholecystectomy to an independence scale. Subtitled
and blinded videos of a novice, an intermediate and an almost competent trainee,
were evaluated with GRSs (OSATS and GOALS) and the independence-scaled procedural
assessment by seven surgeons, three senior trainees and six scrub nurses.
Participants received a short introduction to the GRSs and independence-scaled
procedural assessment before assessment. The validity was estimated with the
Friedman and Wilcoxon test and the reliability with the intra-class correlation
coefficient (ICC). A questionnaire was used to evaluate user opinion. RESULTS:
Independence-scaled procedural assessment and GRS scores improved significantly
with surgical experience (OSATS p = 0.001, GOALS p < 0.001, independence-scaled
procedural assessment p < 0.001). The ICCs of the OSATS, GOALS and independence
scaled procedural assessment were 0.78, 0.74 and 0.84, respectively, among
surgeons. The ICCs increased when the ratings of scrub nurses were added to those
of the surgeons. The independence-scaled procedural assessment was not considered
more of an administrative burden than the GRSs (p = 0.692).
DISCUSSION/CONCLUSION: A procedural assessment created by combining procedural
key steps to an independence scale is a valid, reliable and acceptable assessment
instrument in surgery. In contrast to the GRSs, the reliability of the
independence-scaled procedural assessment exceeded the threshold of 0.8,
indicating that it can also be used for summative assessment. It furthermore
seems that scrub nurses can assess the operative competence of surgical trainees.
PMID- 26416370
TI - Laparoscopic transhiatal esophagectomy improves hospital outcomes and reduces
cost: a single-institution analysis of laparoscopic-assisted and open techniques.
AB - BACKGROUND: Several case series have demonstrated that laparoscopic transhiatal
esophagectomy (LTHE) is associated with favorable perioperative outcomes compared
to historical data for open transhiatal esophagectomy (OTHE). Contemporaneous
evaluation of open and laparoscopic THE is rare, limiting meaningful comparison
of techniques. METHODS: All patients who underwent OTHE (n = 32) and LTHE (n =
41) during the introduction of the latter procedure at our institution (1/2012
4/2014) were identified, and patient charts were retrospectively reviewed.
RESULTS: Indications for operation included 69 patients with esophageal
malignancy (adenocarcinoma: 64; squamous cell carcinoma: 4; melanoma: 1) and 4
patients with benign disease. There were no significant differences in
clinicopathologic variables between OTHE and LTHE cohorts, except for an
increased rate of cardiovascular disease in the LTHE cohort (p = 0.04). There was
no significant difference in median operative time or operative complications,
yet LTHE was associated with a lower incidence of intraoperative blood
transfusion (p < 0.01). There were no 30-day mortalities. LTHE was associated
with a reduced time to reach 24-h tube feeding goals (p = 0.02), shorter length
of hospital stay (p = 0.01), and 6 % reduced median direct cost (p = 0.04). There
were no significant differences in rates of major perioperative morbidities.
Patients were followed for a median of 11.0 months during which there were no
significant differences between cohorts in disease-free survival or overall
survival. CONCLUSION: When compared to OTHE, LTHE improves surgical outcomes and
decreases hospital costs; short-term oncologic outcomes are similar. LTHE is
preferable to OTHE in patients requiring transhiatal esophagectomy.
PMID- 26416371
TI - A novel method of delta-shaped intracorporeal double-tract reconstruction in
totally laparoscopic proximal gastrectomy.
AB - BACKGROUND: The purpose of this study is to depict a novel delta-shaped
intracorporeal double-tract reconstruction (DT) for totally laparoscopic (TL)
proximal gastrectomy (PG), and to evaluate its safety and feasibility by
analyzing its surgical and postoperative outcomes. PATIENTS AND METHODS: We
retrospectively reviewed the cases of 21 patients who underwent TLPG and TLDT
(TLPG-DT) from January to December 2014 in our hospital. The data of
clinicopathologic characteristics, surgical and postoperative outcomes, and
follow-up findings were collected and analyzed. RESULTS: The mean duration of the
operation was 173.8 +/- 21.8 min, including 27.8 +/- 5.3 min of reconstruction.
The blood loss was 109.2 +/- 96.3 mL. The mean number of LNs dissected was 25.7
+/- 4.7. The mean time of the first flatus was at postoperative day 2.3 +/- 1.0,
and the mean postoperative hospital stay was 6.8 +/- 2.5 days. The early
complications rate was 9.5 %, including one intraperitoneal hemorrhage and one
pulmonary infection (both were managed through conservative methods and no re
operation occurred). The rate of complications in late stage was also 9.5 %,
including one diarrhea and one reflux symptom claim. Among the total 21 cases, 17
patients were followed up more than 6 months, showing no signs of reflux
esophagitis or anastomotic stenosis. The mean weight loss in 3 and 6 months after
the operation was 4.3 and 5.7 %, respectively. CONCLUSION: Totally laparoscopic
delta-shaped intracorporeal double-tract reconstruction is a safe, feasible and
minimally invasive reconstruction method with excellent postoperative outcomes in
terms of preventing reflux esophagitis and anastomotic stenosis. TLPG-DT might
serve as a promising treatment for proximal gastric cancer of early stage.
PMID- 26416372
TI - Laparoscopic radical cholecystectomy for suspected early gall bladder carcinoma:
thinking beyond convention.
AB - BACKGROUND: Gall bladder cancer (GBC) is the most common and aggressive
malignancy of the biliary tract with extremely poor prognosis. Radical resection
remains the only potential curative treatment for operable lesions. Although
laparoscopic approach is now considered as standard of care for many
gastrointestinal malignancies, surgical community is still reluctant to use this
approach for GBC probably because of fear of tumor dissemination, inadequate
lymphadenectomy and overall nihilistic approach. Aim of this study was to share
our initial experience of laparoscopic radical cholecystectomy (LRC) for
suspected early GBC. METHODS: From 2008 to 2013, 91 patients were evaluated for
suspected GBC, of which, 14 patients had early disease and underwent LRC.
RESULTS: Mean age of the cohort was 61.14 +/- 4.20 years with male/female ratio
of 1:1.33. Mean operating time was 212.9 +/- 26.73 min with mean blood loss of
196.4 +/- 63.44 ml. Mean hospital stay was 5.14 +/- 0.86 days without any 30-day
mortality. Bile leak occurred in two patients. Out of 14 patients, 12 had
adenocarcinoma, one had xanthogranulomatous cholecystitis and another had
adenomyomatosis of gall bladder as final pathology. Resected margins were free in
all (>1 cm). Median number of lymph nodes resected was 8 (4-14). Pathological
stage of disease was pT2N0 in eight, pT2N1 in three and pT3N0 in one patient.
Median follow-up was 51 (14-70) months with 5-year survival 68.75 %. CONCLUSIONS:
Laparoscopic radical cholecystectomy with lymphadenectomy can be a viable
alternative for management of early GBC in terms of technical feasibility and
oncological clearance along with offering the conventional advantages of minimal
access approach.
PMID- 26416375
TI - SAGES presidential address: a SAGES Magical Mystery Tour.
PMID- 26416373
TI - Safety analysis of primary bariatric surgery in patients on chronic dialysis.
AB - BACKGROUND: Due to the steady increase in patients on chronic dialysis, more of
these patients are undergoing elective operations. The literature on safety and
postoperative outcomes in dialysis-dependent patients following elective
bariatric surgery is scant. We compared the 30-day major morbidity and mortality
rates in dialysis-dependent (DD) and non-dependent (ND) patients after primary
bariatric surgery. METHODS: From American College of Surgeons National Surgical
Quality Improvement Program, we identified patients, who underwent primary
bariatric surgery between 2005 and 2013. Thirty-day postoperative outcomes were
compared between DD and ND patients. Logistic regression was used to determine
the prognostic impact of dependence on chronic dialysis on the 30-day
postoperative outcomes. RESULTS: Two hundred and thirty-four DD and 113,677 ND
patients were analyzed. DD patients had a higher baseline risk profile compared
to ND patients. Thirty-day mortality rates for DD and ND patients were 0.43 and
0.11 %, respectively (P = 0.134). DD patients had a higher 30-day major morbidity
compared to ND patients (5.98 vs. 2.31 %; P < 0.001, respectively). Despite a
crude OR of 2.70 (95 % CI 1.57-4.63) after adjusting for confounding, dependence
on dialysis was not found to be an independent predictor of major morbidity.
CONCLUSIONS: Primary bariatric surgery is safe in patients dependent on dialysis
with an acceptable 30-day postoperative morbidity and mortality. Even though
dependence on dialysis does not independently increase the risk of 30-day adverse
outcomes following primary bariatric surgery, the comorbid conditions in this
patient population render them at risk. The higher prevalence of major
morbidities in this group is mainly due to the impact from older age, male sex,
higher BMI, cardiac comorbidities, and hypertension.
PMID- 26416374
TI - Pros and cons of the gasless laparoscopic transhiatal esophagectomy for upper
esophageal carcinoma.
AB - BACKGROUND: Controversies on how to treat upper esophageal carcinoma have existed
for several decades. With the application of minimally invasive techniques,
surgical treatment to upper esophageal carcinoma tends to show more advantages
and attract more patients. Up to now, most hospitals adopted the combined
thoracoscopic and laparoscopic esophagectomy (CTLE) as the way of minimally
invasive surgery for upper esophageal carcinoma. But CTLE to treat upper
esophageal carcinoma has its drawbacks, such as demanding certain pulmonary
function and severe postoperative regurgitation. In 2011, we developed the
gasless laparoscopic transhiatal esophagectomy (LTE) to treat upper esophageal
carcinoma, which showed some advantages. The aim of this article was to compare
LTE with CTLE in treating upper thoracic or cervical esophageal carcinoma and
assess the value of LTE. METHODS: From 2009 to 2014, esophagectomy has been
performed by the introduction of minimally invasive surgery in a total of 83
patients with upper thoracic or cervical esophageal carcinoma. Among these
patients, LTE was performed in 27 cases (Group 1), while CTLE was performed in
the other 56 (Group 2). Neoadjuvant chemotherapy was done in patients of Group 1.
RESULTS: There were no operation-related deaths and conversion to open procedure.
There was no significant difference in postoperative complications, ventilation
time, ICU stay, hospital stay, and anastomotic leak rates between the two groups.
But LTE was associated with shorter operative time and less intraoperative blood
loss. In Group 2, 21 (37.5 %) patients had postoperative pulmonary complications,
while in Group 1, there were 6 (22.2 %) patients having pulmonary complications
at least one time. Results of 24-h pH monitoring and manometry showed that
postoperative laryngo-pharyngeal reflux (PLPR) was more severe in Group 2
patients than in Group 1; for Group 1, PLPR mainly occurred on sleep stage, while
for Group 2, PLPR might exist all the day with short intervals and last longer at
night. The median overall survival was 27.2 months after CTLE and 30.8 months
after LTE (P = 0.962). There was no significant difference in survival at 2, 3
and 4 years between the two groups. CONCLUSIONS: Compared with CTLE, LTE is a
more minimally invasive approach to effectively treat patients with upper
esophageal carcinoma. Laryngo-pharyngeal reflux after LTE was less severe than
that after CTLE, which might lower incidence of pulmonary complications. For the
elderly patients, LTE seems more suitable.
PMID- 26416376
TI - The utility of radiological upper gastrointestinal series and clinical indicators
in detecting leaks after laparoscopic sleeve gastrectomy: a case-controlled
study.
AB - BACKGROUND: Leak after laparoscopic sleeve gastrectomy (LSG) often presents after
hospital discharge, making timely diagnosis difficult. This study evaluates the
utility of radiological upper gastrointestinal (UGI) series and clinical
indicators in detecting leak after LSG. METHODS: A retrospective case-controlled
study of 1762 patients who underwent LSG from 2006 to 2014 was performed. All
patients with radiographically confirmed leaks were included. Controls consisted
of patients who underwent LSG without leak, selected using a 10:1 case-match.
Data included baseline patient characteristics, surgical characteristics, and UGI
series results. Clinical indicators including vital signs, SIRS criteria, and
pain score were compared between patients who developed leak and controls.
RESULTS: Of 1762 LSG operations, 20 (1.1 %) patients developed leaks and were
compared with 200 case-matched controls. Three patients developed leak during
their index admission [mean = 1.3 days, range (1, 2)], while the majority (n =
17) were discharged and developed symptoms at a mean of 17.1 days [range (4, 63)]
postoperatively. Patients diagnosed with leak were similar to controls in
baseline and surgical characteristics. Contrast extravasation on routine
postoperative UGI identified two patients with early leaks, but was negative in
the remainder (89 %). Patients with both early and delayed leaks demonstrated
significant clinical abnormalities at the time of leak presentation, prior to
confirmatory radiographic study. In multiple regression analysis, independent
clinical factors associated with leak included fever [OR 16.6, 95 % CI (4.04,
68.10), p < 0.0001], SIRS criteria [OR 7.0, 95 % CI (1.47, 33.26), p = 0.014],
and pain score >=9 [OR 19.1, 95 % CI (1.38, 263.87), p = 0.028]. CONCLUSIONS:
Contrast extravasation on routine postoperative radiological UGI series may
detect early leaks after LSG, but the vast majority of leaks demonstrate normal
results and present 2-3 weeks after discharge. Therefore, clinical indicators
(specifically fever, SIRS criteria, and pain score) are the most useful factors
to raise concern for leaks prior to confirmatory radiographic study and may be
used as criteria to selectively obtain UGI studies after LSG.
PMID- 26416377
TI - Evaluating quality across minimally invasive platforms in colorectal surgery.
AB - INTRODUCTION: There is an increasing emphasis on optimizing and measuring
surgical quality. The safety and efficacy of minimally invasive techniques have
been proven; however, direct comparison of outcomes across platforms has not been
performed. Our goal was to compare operative times and quality across three
minimally invasive platforms in colorectal surgery. METHODS: A prospective
database was reviewed for elective minimally invasive surgery (MIS) cases from
2008 to 2014. Patients were stratified into multiport laparoscopic, single
incision laparoscopic (SILS) or robotic-assisted laparoscopic approaches (RALS).
Demographics, perioperative, and postoperative outcomes were analyzed.
Multivariate regression analysis was used to predict the demographic and
procedural factors and outcomes associated with each platform. The main outcome
measures were operative time and surgical quality by approach. RESULTS: A total
of 1055 cases were evaluated-28.4 % LAP, 18.5 % RALS, and 53.1 % SILS. RALS had
the most complex patients, pathology, and procedures. The main diagnosis for RALS
was rectal cancer (49.5 %), patients predominantly underwent pelvic surgery (72.8
%), had higher rates of neoadjuvant chemoradiation (p < 0.001) and stoma creation
(p < 0.001). RALS had the longest operative time and highest complication and
readmissions rates (all p < 0.001). Multiport patients were older than SILS and
RALS (p = 0.021), had the most intraoperative complications (p < 0.001),
conversions (p < 0.001), and had the longest length of stay (p = 0.001). SILS had
the shortest operative times (p < 0.001), length of stay (p = 0.001), and lowest
rates of complications (p < 0.001), readmissions (p < 0.001), and unplanned
reoperation (p = 0.014). All platforms offered high quality (HARM score 0) from
overall short LOS, low readmission, and mortality rates. CONCLUSIONS: Multiport,
RALS, and SILS each serve a distinct demographic and disease profile and have
predictable outcomes. All have risks and benefits, but offer overall high-quality
care with a composite of LOS, readmission, and mortality rates. Operative times
were directly associated with readmission rates. As all three platforms offer
good quality, the choice of which MIS approach to use should be guided by
demographics and disease process.
PMID- 26416378
TI - Laparoscopic deroofing for polycystic liver disease using laparoscopic fusion
indocyanine green fluorescence imaging.
AB - BACKGROUND: Laparoscopic deroofing is widely used for the treatment of
symptomatic polycystic liver disease (PCLD). However, bile leakage is a common
complication of surgical management for PCLD. Until now, indocyanine green
fluorescence imaging (IGFI) has played an active role in hepatobiliary surgery.
Herein, we report the effective application of a laparoscopic fusion IGFI system,
known as PINPOINT, for laparoscopic deroofing. METHODS: In this study, we
performed laparoscopic deroofing for PCLD using the laparoscopic fusion IGFI
system. We conducted the procedure mainly under the normal view mode,
occasionally switching to the fusion IGFI mode. First, we confirmed that the
liver cysts did not contain bile using the fusion IGFI mode and then used a
percutaneous puncture needle to remove the fluid from some of the giant cysts.
Second, using the fusion IGFI mode, we were able to detect thin biliary branches
and to adjust the division line of the cyst wall accordingly or, occasionally, to
ligate the branches. Finally, we searched for and identified unexpected small
bile leakage and then closed it using sutures. RESULTS: The laparoscopic fusion
IGFI system can simultaneously show fluorescent images, such as cholangiography
and the liver parenchyma, on the normal color view. In the fusion IGFI mode, the
intrahepatic bile duct and liver parenchyma can be easily discriminated in real
time throughout the procedure. Accordingly, the laparoscopic fusion IGFI system
is useful for the surgical treatment of PCLD, in which the boundary between the
liver cysts and the liver parenchyma can otherwise be difficult to identify. This
technique also enables the branches of Glisson's capsule to be identified without
any other intervention. CONCLUSION: The novel application of the laparoscopic
fusion IGFI system allows reliable navigation for PCLD surgery.
PMID- 26416379
TI - Stent-in-stent technique for removal of embedded partially covered self-expanding
metal stents.
AB - BACKGROUND: Removal of embedded partially covered self-expanding metal stents
(PCSEMS) is associated with an increased risk of adverse events compared with
removal of fully covered self-expanding stents (FCSES) due to tissue ingrowth.
Successful removal of embedded PCSEMS has been described by the stent-in-stent
(SIS) technique. AIMS: To report the first US experience from three high-volume
quaternary care centers on the safety and efficacy of the SIS technique for
removal of embedded PCSEMS. METHODS: Retrospective study of outcomes for
consecutive patients who underwent the SIS for removal of embedded PCSEMS over a
5-year period. RESULTS: Twenty-seven embedded PCSEMS were successfully removed
using the SIS technique (100 %) from 25 patients (11 males), median age 65 (range
37-80). All stents were successfully removed in one endoscopic session (no repeat
SIS procedures were required for persistently embedded stents). The embedded
PCSEMS had been in situ for a median of 76 days (range 26-501). Median SIS dwell
time (FCSES in situ of PCSEMS) was 13 days (interquartile range 8-16 days; range
4-212 days). One adverse event (self-limited bleeding) occurred during a median
follow-up period of 3 months (range 1-32). No patients died, required surgery, or
had long-term disability due to adverse events attributed to the SIS technique.
Twelve patients required additional interventions following SIS procedure for
persistence or recurrence of the underlying pathology. CONCLUSION: When performed
by experienced endoscopists, safe and effective removal of embedded PCSEMS can be
achieved via the SIS technique.
PMID- 26416380
TI - Management of non-acute gastrointestinal defects using the over-the-scope clips
(OTSCs): a retrospective single-institution experience.
AB - INTRODUCTION: Advanced endoscopic techniques provide novel therapies for
complications historically treated with surgical interventions. Over-the-scope
clips (OTSCs) have recently been shown to be effective at endoscopic closure of
gastrointestinal (GI) defects. We hypothesize that by following classic surgical
principles of fistula management, a high rate of long-term success can be
achieved with endoscopic closure of non-acute GI tract defects. METHODS: A
retrospective review of a single-institution prospectively maintained database
(2012-2015) of all patients referred for the management of GI leaks or fistulae
who underwent attempted closure with the OTSC system (Ovesco, Germany) was
performed. Acute perforations were excluded. The primary endpoint was long-term
success defined by the absence of radiographic or clinical evidence of leak or
fistula during follow-up. Patients were stratified by success or failure of OTSC
closure and compared with Fisher's exact and Mann-Whitney U tests. RESULTS: We
identified 22 patients with 28 defects (22 fistulae and 6 leaks). Most patients
were female (59 %) with a mean age of 54 years (+/-14), median BMI of 29, and
prior bariatric procedure (55 %). Comorbidities included smoking history (68 %)
and diabetes (23 %). The majority of defects were solitary (64 %), involved the
upper GI tract (82 %), and had been present for >30 days (50 %). Multiple
therapeutic interventions were necessary in 46 % of defects. There were no
adverse outcomes related to OTSC placement or misfiring. Endoscopic adjuncts were
used in 61 % of cases. Overall success rate was 82 % (100 % for leaks and 76 %
for fistulae) at a median follow-up of 4.7 months (IQR 2.1-8.4 months).
Predictors of success and failure could not be distinguished due to limited
sample size. CONCLUSIONS: Over-the-scope clips can be safely and effectively used
in patients presenting with GI leaks and fistulae. Further research is required
to characterize the determinants of long-term success and risk factors for
failure.
PMID- 26416381
TI - A prospective analysis of GERD after POEM on anterior myotomy.
AB - BACKGROUND: Peroral endoscopic myotomy (POEM) is an emerging, minimally invasive
procedure capable of overcoming limitations of achalasia treatments, but
gastroesophageal reflux disease (GERD) after POEM is of concern and its risk
factors have not been evaluated. This prospective study examined GERD and the
association of POEM with reflux esophagitis. METHODS: Achalasia patients were
recruited from a single center. The pre- and postoperative assessments included
Eckardt scores, manometry, endoscopy, and pH monitoring. RESULTS: Between
September 2011 and November 2014, 105 patients underwent POEM; 70 patients were
followed up 3 months after POEM. Postoperatively, significant reductions were
observed in lower esophageal sphincter (LES) pressure [from 40.0 +/- 22.8 to 20.7
+/- 14.0 mmHg (P < 0.05)], LES residual pressure [from 22.1 +/- 13.3 to 11.4 +/-
6.6 mmHg (P < 0.05)], and Eckardt scores [from 5.7 +/- 2.5 to 0.7 +/- 0.8 (P <
0.05)]. Symptomatic GERD and moderate reflux esophagitis developed in 5 and 11
patients (grade B, n = 8; grade C, n = 3), respectively, and were well controlled
with proton pump inhibitors. Univariate logistic regression analysis revealed
integrated relaxation pressure was a predictor of >=grade B reflux esophagitis.
No POEM factors were found to be associated with reflux esophagitis. CONCLUSION:
POEM is effective and safe in treating achalasia, with no occurrence of
clinically significant refractory GERD. Myotomy during POEM, especially of the
gastric side, was not associated with >=grade B (requiring medical intervention)
reflux esophagitis. Extended gastric myotomy (2-3 cm) during POEM is recommended
to improve outcomes.
PMID- 26416382
TI - Flower-like supramolecular self-assembly of phosphonic acid appended naphthalene
diimide and melamine.
AB - Diverse supramolecular assemblies ranging from nanometres to micrometers of small
aromatic pi-conjugated functional molecules have attracted enormous research
interest in light of their applications in optoelectronics, chemosensors,
nanotechnology, biotechnology and biomedicines. Here we study the mechanism of
the formation of a flower-shaped supramolecular structure of phosphonic acid
appended naphthalene diimide with melamine. The flower-shaped assembly formation
was visualised by scanning electron microscope (SEM) and transmission electron
microscopy (TEM) imaging, furthermore, XRD and DLS used to determined mode of
aggregation. Characteristically, phosphonic acid-substituted at imide position of
NDIs possess two important properties resulting in the formation of controlled
flower-like nanostructures: (i) the aromatic core of the NDI which is designed to
optimize the dispersive interactions (pi-pi stacking and van der Waals
interactions) between the cores within a construct and (ii) phosphonic acid of
NDI interact with malamine through molecular recognition i.e. strong hydrogen
bonding (H-bonding). We believe such arrangements prevent crystallization and
favour the directional growth of flower-like nanostructure in 3D fashion. These
works demonstrate that complex self-assembly can indeed be attained through
hierarchical non-covalent interactions of two components. Furthermore, flower
like structures built from molecular recognition by these molecules indicate
their potential in other fields if combined with other chemical entities.
PMID- 26416383
TI - Multilocus species trees and species delimitation in a temporal context:
application to the water shrews of the genus Neomys.
AB - BACKGROUND: Multilocus data are becoming increasingly important in determining
the phylogeny of closely related species and delimiting species. In species
complexes where unequivocal fossil calibrations are not available, rigorous
dating of the coalescence-based species trees requires accurate mutation rates of
the loci under study but, generally, these rates are unknown. Here, we obtained
lineage-specific mutation rates of these loci from a higher-level phylogeny with
a reliable fossil record and investigated how different choices of mutation rates
and species tree models affected the split time estimates. We implemented this
strategy with a genus of water shrews, Neomys, whose taxonomy has been
contentious over the last century. RESULTS: We sequenced 13 introns and
cytochrome b from specimens of the three species currently recognized in this
genus including two subspecies of N. anomalus that were originally described as
species. A Bayesian multilocus species delimitation method and estimation of gene
flow supported that these subspecies are distinct evolutionary lineages that
should be treated as distinct species: N. anomalus (sensu stricto), limited to
part of the Iberian Peninsula, and N. milleri, with a larger Eurasian range. We
then estimated mutation rates from a Bayesian relaxed clock analysis of the
mammalian orthologues with several fossil calibrations. Next, using the estimated
Neomys-specific rates for each locus in an isolation-with-migration model, the
split time for these sister taxa was dated at 0.40 Myr ago (with a 95 %
confidence interval of 0.26 - 0.86 Myr), likely coinciding with one of the major
glaciations of the Middle Pleistocene. We also showed that the extrapolation of
non-specific rates or the use of simpler models would lead to very different
split time estimates. CONCLUSIONS: We showed that the estimation of rigorous
lineage-specific mutation rates for each locus allows the inference of robust
split times in a species tree framework. These times, in turn, afford a better
understanding of the timeframe required to achieve isolation and, eventually,
speciation in sister lineages. The application of species delimitation methods
and an accurate dating strategy to the genus Neomys helped to clarify its
controversial taxonomy.
PMID- 26416384
TI - Association of DNA methyltransferases expression with global and gene-specific
DNA methylation in colorectal cancer cells.
AB - There are conflicting reports regarding the association between DNA
methyltransferases (DNMTs) expression and global or gene-specific DNA methylation
in colorectal cancer (CRC) cells. To correlate DNMTs expression with DNA
methylation, we quantified DNMT1, DNMT3A and DNMT3B mRNA levels in five CRC cell
lines (HCT116, LS180, HT29/219, Caco2 and SW742) by real-time reverse
transcriptase polymerase chain reaction (PCR) assay. In addition, we examined the
global 5-methyl cytosine levels and the methylation patterns of 12 CpG islands in
these CRC cells by enzyme-linked immunosorbent assay and methylation-specific PCR
methods, respectively. The average expression levels of three DNMTs in HCT116,
Caco2, HT29/219 and SW742, relative to the expression level in LS180 (taken to be
1), were 90.1, 31.6, 2.66 and 1.86. Our data indicated that overall about 1.45%,
1.03%, 0.98%, 0.86% and 0.85% of the cytosines were methylated in the genome of
HCT116, Caco2, HT29/219, SW742 and LS180 cells, respectively. The 5-mC
percentages were positively correlated with the relative cellular DNMTs
expression in five CRC cell lines as verified by Pearson correlation test.
However, we found no positive correlation between mRNA expression of DNMTs and
gene promoter hypermethylation in these cells. Our results suggest that cellular
DNMT expression is positively correlated with global DNA methylation level but
not with regional DNA hypermethylation at each locus.
PMID- 26416385
TI - Phenylephrine Pharmacokinetics and First-Pass Metabolism: What Is an Ideal
Pharmacokinetic Surrogate?
PMID- 26416386
TI - Rates of motorcycle helmet use and reasons for non-use among adults and children
in Luang Prabang, Lao People's Democratic Republic.
AB - BACKGROUND: Motorcycles make up 81 % of the total vehicle population and 74 % of
road traffic deaths in Lao PDR. Helmets reduce the risk and severity of injuries
resulting from motorcycle accidents by 72 %. Although Lao law mandates motorcycle
helmet use among drivers and passengers, the prevalence of helmet use in Luang
Prabang, Lao PDR is unknown. This project aimed to measure the prevalence of
motorcycle helmet use among riders (i.e., drivers and passengers) in Luang
Prabang. METHODS: An observational survey in Luang Prabang was conducted in
February 2015 to measure the prevalence of motorcycle helmet use among drivers
and passengers. Additionally, non-helmet wearing riders were surveyed to identify
the reasons for helmet non-use. RESULTS: Of 1632 motorcycle riders observed, only
16.2 % wore helmets. Approximately 29 % of adults wore helmets while less than 1
% of all children wore helmets. When surveyed about attitudes towards helmet use,
the majority of adult drivers indicated that they did not like how adult helmets
feel or made them look. Additionally, almost half of motorcyclists who did not
own child helmets reported that their child was too young to wear a helmet.
CONCLUSIONS: Our finding that children wear helmets at significantly lower rates
compared to adults is consistent with findings from neighboring countries in
Southeast Asia. Results of this study have implications for public health
campaigns targeting helmet use, especially among children.
PMID- 26416387
TI - Missing steps in a staircase: a qualitative study of the perspectives of key
stakeholders on the use of adaptive designs in confirmatory trials.
AB - BACKGROUND: Despite the promising benefits of adaptive designs (ADs), their
routine use, especially in confirmatory trials, is lagging behind the prominence
given to them in the statistical literature. Much of the previous research to
understand barriers and potential facilitators to the use of ADs has been driven
from a pharmaceutical drug development perspective, with little focus on trials
in the public sector. In this paper, we explore key stakeholders' experiences,
perceptions and views on barriers and facilitators to the use of ADs in publicly
funded confirmatory trials. METHODS: Semi-structured, in-depth interviews of key
stakeholders in clinical trials research (CTU directors, funding board and panel
members, statisticians, regulators, chief investigators, data monitoring
committee members and health economists) were conducted through telephone or face
to-face sessions, predominantly in the UK. We purposively selected participants
sequentially to optimise maximum variation in views and experiences. We employed
the framework approach to analyse the qualitative data. RESULTS: We interviewed
27 participants. We found some of the perceived barriers to be: lack of knowledge
and experience coupled with paucity of case studies, lack of applied training,
degree of reluctance to use ADs, lack of bridge funding and time to support
design work, lack of statistical expertise, some anxiety about the impact of
early trial stopping on researchers' employment contracts, lack of understanding
of acceptable scope of ADs and when ADs are appropriate, and statistical and
practical complexities. Reluctance to use ADs seemed to be influenced by:
therapeutic area, unfamiliarity, concerns about their robustness in decision
making and acceptability of findings to change practice, perceived complexities
and proposed type of AD, among others. CONCLUSIONS: There are still considerable
multifaceted, individual and organisational obstacles to be addressed to improve
uptake, and successful implementation of ADs when appropriate. Nevertheless,
inferred positive change in attitudes and receptiveness towards the appropriate
use of ADs by public funders are supportive and are a stepping stone for the
future utilisation of ADs by researchers.
PMID- 26416388
TI - Effectiveness of agalsidase alfa enzyme replacement in Fabry disease: cardiac
outcomes after 10 years' treatment.
AB - BACKGROUND: To explore long-term effects of agalsidase alfa on Fabry disease
cardiomyopathy in adults. METHODS: Retrospective analysis of prospectively
collected data at a single center in Mainz, Germany, revealed that 45 adult
patients (21 men, 24 women) had received agalsidase alfa for approximately 10
years. Data were extracted for cardiac and heart failure status,
echocardiographic evaluations of cardiac structure and function, and renal
function at treatment start and during agalsidase alfa treatment. RESULTS: After
10 years of agalsidase alfa treatment, heart failure classification had improved
by at least 1 class in 22/42 patients, and angina scores were stable or improved
in 41/42 patients. During treatment, no patients without left ventricular
hypertrophy (LVH) at treatment initiation developed LVH, and no patients with LVH
at treatment initiation showed a decline in left ventricular mass. CONCLUSIONS:
Approximately 10 years of agalsidase alfa treatment appeared to have beneficial
effects for controlling progression and improving some symptoms of Fabry
associated cardiomyopathy.
PMID- 26416389
TI - Discriminating nutritional quality of foods using the 5-Color nutrition label in
the French food market: consistency with nutritional recommendations.
AB - PURPOSE: Our objectives were to assess the performance of the 5-Colour nutrition
label (5-CNL) front-of-pack nutrition label based on the Food Standards Agency
nutrient profiling system to discriminate nutritional quality of foods currently
on the market in France and its consistency with French nutritional
recommendations. METHODS: Nutritional composition of 7777 foods available on the
French market collected from the web-based collaborative project Open Food Facts
were retrieved. Distribution of products across the 5-CNL categories according to
food groups, as arranged in supermarket shelves was assessed. Distribution of
similar products from different brands in the 5-CNL categories was also assessed.
Discriminating performance was considered as the number of color categories
present in each food group. In the case of discrepancies between the category
allocation and French nutritional recommendations, adaptations of the original
score were proposed. RESULTS: Overall, the distribution of foodstuffs in the 5
CNL categories was consistent with French recommendations: 95.4% of 'Fruits and
vegetables', 72.5% of 'Cereals and potatoes' were classified as 'Green' or
'Yellow' whereas 86.0% of 'Sugary snacks' were classified as 'Pink' or 'Red'.
Adaptations to the original FSA score computation model were necessary for
beverages, added fats and cheese in order to be consistent with French official
nutritional recommendations. CONCLUSION: The 5-CNL label displays a high
performance in discriminating nutritional quality of foods across food groups,
within a food group and for similar products from different brands. Adaptations
from the original model were necessary to maintain consistency with French
recommendations and high performance of the system.
PMID- 26416390
TI - Service users' and carers' views on research towards stratified medicine in
psychiatry: a qualitative study.
AB - BACKGROUND: Approximately 30% of people with a diagnosis of schizophrenia receive
little to no benefit from current medications. There is therefore an urgent need
to develop more precisely targeted and effective treatments. Identifying
biomarkers to predict response to treatment and stratify patients into groups may
be a way forward. However, we know little about service users' and carers'
attitudes regarding such a 'stratified medicine' approach for psychiatry-nor how
this might impact on their willingness to participate in stratified medicine
research. This paper presents psychiatric service user and carer views on
research to develop stratified medicine for treatment resistant schizophrenia,
and explores the conditions under which people would be prepared to participate
in a trial and their willingness to undergo various research procedures. METHODS:
Participatory methods were used throughout. A consultation was undertaken with an
existing Service User Advisory Group (SUAG) in order to establish a topic guide.
Service user focus groups were then conducted by service user researchers in
Manchester, London and Edinburgh (totalling 18 people) and one carer focus group
in London, attended by eight participants. Focus groups were digitally recorded,
the transcripts analysed in NVivo 10 using a simple thematic analysis, and
quotations de-identified to protect participants. RESULTS: The data reflected
enthusiasm for the potential of stratified medicine and both service users and
carers demonstrated a strong desire to help others. However, some service users
and carers feared poor performance on neuropsychological assessments, and
reported that certain medication side effects might discourage them from
undergoing procedures demanding immobility and concentration. Concerns were
voiced that stratified medicine could encourage an overemphasis on biological
symptoms, at the expense of psychosocial factors and subjective experience.
CONCLUSIONS: People with experience of treatment resistant schizophrenia would
welcome stratified medicine research; however researchers should take into
account how such experience might inflect service users' willingness to undergo
various procedures in the context of this research. These results reinforce the
value of service user perspectives in the development and evaluation of novel
treatment approaches.
PMID- 26416392
TI - Factors affecting (223)Ra therapy: clinical experience after 532 cycles from a
single institution.
AB - PURPOSE: The aim of this study was to identify baseline features that predict
outcome in (223)Ra therapy. METHODS: We retrospectively reviewed 110 patients
with metastatic castration-resistant prostate cancer treated with (223)Ra. End
points were overall survival (OS), progression-free survival (PFS), bone event
free survival (BeFS), and bone marrow failure (BMF). The following parameters
were evaluated prior to the first (223)Ra cycle: serum levels of hemoglobin (Hb),
prostate-specific antigen (PSA), alkaline phosphatase (ALP), Eastern Cooperative
Oncology Group (ECOG) status, pain score, use of chemotherapy, and external beam
radiation therapy (EBRT). During/after (223)Ra we evaluated: the total number of
radium cycles (RaTot), the PSA doubling time (PSADT), and the use of
chemotherapy, EBRT, abiraterone, and enzalutamide. RESULTS: A significant
reduction of ALP (p < 0.001) and pain score (p = 0.041) occurred throughout the
(223) Ra cycles. The risk of progression was associated with declining ECOG
status [hazard ratio (HR) = 3.79; p < 0.001] and decrease in PSADT (HR = 8.22; p
< 0.001). RaTot, ALP, initial ECOG status, initial pain score, and use of
abiraterone were associated with OS (p <= 0.008), PFS (p <= 0.003), and BeFS (p
<= 0.020). RaTot, ALP, initial ECOG status, and initial pain score were
significantly associated with BMF (p <= 0.001) as well as Hb (p < 0.001) and EBRT
(p = 0.009). On multivariable analysis, only RaTot and abiraterone remained
significantly associated with OS (p < 0.001; p = 0.033, respectively), PFS (p <
0.001; p = 0.041, respectively), and BeFS (p < 0.001; p = 0.019, respectively).
Additionally, RaTot (p = 0.027) and EBRT (p = 0.013) remained significantly
associated with BMF. CONCLUSION: Concomitant use of abiraterone and (223)Ra seems
to have a beneficial effect, while the EBRT may increase the risk of BMF.
PMID- 26416393
TI - IL-1A rs1800587, IL-1B rs1143634 and IL-1R1 rs2234650 polymorphisms in Iranian
patients with systemic sclerosis.
AB - Systemic Sclerosis (SSc) is a systemic autoimmune disorder, with ambiguous
pathogenesis. Genetic and environmental factors were proved to be correlated with
SSc aetiology. Single nucleotide polymorphisms (SNPs) in cytokine genes can alter
the structure and function of the cytokines and consequently may increase the
susceptibility to a specific disease. In this study, we investigated SNPs of the
IL-1 gene cluster in Iranian SSc patients. We obtained blood samples from 170 SSc
patients and 213 healthy individuals. Cytokine genotyping results were obtained
by polymerase chain reaction with sequence-specific primers (PCR-SSP). IL-1A
rs1800587, IL-1B rs1143634 and IL-1R1 rs2234650 were evaluated for SNP study. The
frequency of the IL-1B rs1143634 CT genotype was significantly lower in SSc
patients compared to the controls (OR = 0.584; 95% CI = 0.385-0.886; P-value =
0.023), so we propose that CT genotype of this allele might be protective.
According to our haplotype analysis, CCC haplotype frequency is higher in the
control group compared to SSc patients (OR = 1.575; 95% CI = 1.176-2.111; P-value
= 0.008) and in contrast, CTC haplotype frequency is lower in the control group
compared to SSc patients (OR = 0.152; 95% CI = 0.047-0.484; P-value = 0.002), so
they might decrease and increase the susceptibility of having SSc, respectively.
In addition, we reported two significant diplotypes frequency differences among
SSc patients and healthy individuals. It is highly important that there is not
much resemblance between the IL-1 gene cluster polymorphism in different
populations, so we can indicate that SNPs may play critical roles when they are
combined with other genetic and environmental factors.
PMID- 26416391
TI - Reliability of radioisotope-guided sentinel lymph node biopsy in penile cancer:
verification in consideration of the European guidelines.
AB - BACKGROUND: Lymph node (LN) staging in penile cancer has strong prognostic
implications. This contrasts with the high morbidity of extended inguinal LN
dissection (LND) or over-treatment of many patients. Therefore, inguinal dynamic
sentinel node biopsy (DSNB) or modified LND is recommended by the European
Association of Urology (EAU) guidelines to evaluate the nodal status of patients
with clinically node-negative penile cancer. This study analyzed the reliability
and morbidity of radioguided DSNB in penile cancer under consideration of the
current EAU recommendations in an experienced center with long-term follow-up.
METHODS: Thirty-four patients who received primary surgery and had radioguided
inguinal DSNB for penile cancer (>= T1G2) were included (July 2004 to July 2013).
Preoperative sentinel LN (SLN) mapping was performed using lymphoscintigraphy
after peritumoral injection of (99m)Technetium nanocolloid on the day of surgery.
During surgery, SLNs were detected using a gamma probe. According to the EAU
guidelines, a secondary ipsilateral radical inguinal LND was performed in
patients who had positive SLNs. The false-negative and complication rates of DSNB
were assessed. RESULTS: A total of 32 patients were analyzed. Two patients were
lost to follow-up. A total of 166 SLNs (median, 5; range, 1-15) were removed and
216 LNs (SLNs + non-SLNs; median, 6; range, 2-19) were dissected. LN metastases
were found in five of the 32 (15.6 %) patients and nine of the 166 (5.4 %) SLNs
were found to contain metastases. None of the remaining 50 non-SLNs contained
metastases. In only one of the five SLN-positive patients, a singular further
metastasis was detected by secondary radical inguinal LND. During follow-up
(median, 30.5; range, 5-95 months) no inguinal nodal recurrence was detected.
DSNB-related complications occurred in 11.1 % of explored groins. DISCUSSION AND
CONCLUSIONS: Radioguided DSNB is a suitable procedure for LN staging in penile
cancer considering the EAU recommendations and with the required experience.
Under these circumstances, patients can be spared from higher morbidity without
compromising the detection of LN metastases or therapeutic implications.
Improvement of the methodology used to perform DSNB should be developed further
to decrease the risk of missing LN metastases and to simplify the procedure.
PMID- 26416394
TI - Levetiracetam for the treatment of status epilepticus.
AB - Status epilepticus (SE) is a common, severe neurological disorder, and prolonged
seizures in SE may result in irreversible brain damage in association with high
disability and mortality rates. Thus, termination of seizures as soon as possible
is vital for the successful treatment of this disease. Levetiracetam, a new broad
spectrum anti-epileptic drug, can be used to rapidly and effectively control SE
episodes with few side effects. Thus, an understanding of the use of this drug to
treat SE will help clinicians to more effectively control SE and improve patient
prognosis.
PMID- 26416395
TI - Management of epilepsy during pregnancy.
AB - Over a million women with epilepsy are of childbearing age in the USA and require
careful consideration of not only type of antiepileptic drug (AED) but also
dosage, in the event of a planned or unplanned pregnancy. Careful selection of
AEDs can lower the potential adverse effects of AEDs while maintaining seizure
control for the health of not only on the patient, the mother, but also the
unborn fetus. The number of treatment options has increased significantly in the
last 20 years and remarkable progress has been made in characterizing the risks
AEDs pose to pregnant women and fetuses. There are now robust data on
teratogenesis, a growing body of data on neonatal/obstetrical outcomes and on
neurodevelopmental problems associated with each AED, and some data about seizure
control during pregnancy. Based on clinical evidence so far, levetiracetam and
lamotrigine have emerged as the safest during pregnancy, although others may also
be suitable. Despite being a common belief, not all polytherapy combinations may
be detrimental, especially when avoiding valproate and topiramate. Here, we
review the available clinical research, highlighting recent findings and provide
thoughts for future directions in the field.
PMID- 26416396
TI - Recognition and treatment of autonomic disturbances in Parkinson's disease.
AB - Symptoms of dysautonomia are common in Parkinson's disease (PD), and almost all
the functional autonomic subsystems can be involved in PD. However, they are
still under-recognized in everyday clinical practice. Autonomic dysfunction can
be observed in the early stages of PD, affect a substantial proportion of
patients, impact quality of life and can also help in differential diagnosis.
This review aims to provide an overview of the pathophysiology, clinical
manifestations, relevant examination and treatment of cardiovascular,
gastrointestinal, urogenital, thermoregulatory and pupil autonomic dysfunctions
in Parkinson's disease.
PMID- 26416397
TI - The relevance of pre-motor symptoms in Parkinson's disease.
AB - Parkinson's disease (PD) has a wide range of non-motor symptoms including;
constipation, sleep disturbance, deficits in vision and olfaction, mood disorders
and cardiac autonomic dysfunction. Several of these non-motor symptoms can
manifest prior to the onset of motor symptoms. Recognizing these pre-motor
symptoms may enable early diagnosis of PD. Currently, no single pre-motor symptom
is able to predict the development of PD with 100% sensitivity or specificity.
Ongoing studies in several independent at-risk cohorts should reveal the
potential of combinations of pre-motor symptoms and multi-stage screening
strategies to identify individuals at increased risk of PD. PD progression may be
governed by a prion-like spread of a-syn throughout the nervous system.
Identifying individuals at the earliest stage will likely be critical to
preventing the pathological progression of PD, highlighting the relevance of pre
motor symptoms in the future treatment of the disease.
PMID- 26416398
TI - A parsimonious statistical method to detect groupwise differentially expressed
functional connectivity networks.
AB - Group-level functional connectivity analyses often aim to detect the altered
connectivity patterns between subgroups with different clinical or psychological
experimental conditions, for example, comparing cases and healthy controls. We
present a new statistical method to detect differentially expressed connectivity
networks with significantly improved power and lower false-positive rates. The
goal of our method was to capture most differentially expressed connections
within networks of constrained numbers of brain regions (by the rule of
parsimony). By virtue of parsimony, the false-positive individual connectivity
edges within a network are effectively reduced, whereas the informative
(differentially expressed) edges are allowed to borrow strength from each other
to increase the overall power of the network. We develop a test statistic for
each network in light of combinatorics graph theory, and provide p-values for the
networks (in the weak sense) by using permutation test with multiple-testing
adjustment. We validate and compare this new approach with existing methods,
including false discovery rate and network-based statistic, via simulation
studies and a resting-state functional magnetic resonance imaging case-control
study. The results indicate that our method can identify differentially expressed
connectivity networks, whereas existing methods are limited.
PMID- 26416399
TI - Simulation and prediction of protein production in fed-batch E. coli cultures: An
engineering approach.
AB - An overall model describing the dynamic behavior of fed-batch E. coli processes
for protein production has been built, calibrated and validated. Using a
macroscopic approach, the model consists of three interconnected blocks allowing
simulation of biomass, inducer and protein concentration profiles with time. The
model incorporates calculation of the extra and intracellular inducer
concentration, as well as repressor-inducer dynamics leading to a successful
prediction of the product concentration. The parameters of the model were
estimated using experimental data of a rhamnulose-1-phosphate aldolase-producer
strain, grown under a wide range of experimental conditions. After validation,
the model has successfully predicted the behavior of different strains producing
two different proteins: fructose-6-phosphate aldolase and omega-transaminase. In
summary, the presented approach represents a powerful tool for E. coli production
process simulation and control.
PMID- 26416400
TI - Reverse sural flap with an adipofascial extension for reconstruction of soft
tissue defects with dead spaces in the heel and ankle.
AB - INTRODUCTION: The reconstruction of soft tissue defects with dead spaces in the
heel and ankle is challenging. This article describes our experience in the
reconstruction of such defects using the reverse sural flap with an adipofascial
extension. METHOD: Reverse sural flaps with an adipofascial extension were used
in 26 patients with soft tissue defects in the heel (n = 24) or ankle (n = 2).
Extended adipofascial tissue was utilized to fill the dead space. The sizes of
the adipofascial extensions varied from 2.0 to 5.0 cm in length and 4.0 to 12.5
cm in width. RESULT: Twenty-three flaps survived completely, and lateral marginal
necrosis occurred in three flaps. All the recipient-site wounds healed without
any signs of infection. The reconstruction outcomes were excellent in 20 patients
and good in 6 patients according to the criteria of Boyden et al. CONCLUSION: The
extended adipofascial tissue of the reverse sural flap improves closure of the
dead spaces in soft tissue defects of the heel and ankle and thus provides
beneficial conditions for the treatment of infection and reconstruction of both
the function and contour of the soft tissue defects with dead spaces in the heel
and ankle.
PMID- 26416401
TI - Non operative management of blunt splenic trauma: a prospective evaluation of a
standardized treatment protocol.
AB - PURPOSE: The advantages of the conservative approach for major spleen injuries
are still debated. This study was designed to evaluate the safety and
effectiveness of NOM in the treatment of minor (grade I-II according with the
American Association for the Surgery of Trauma; AAST) and severe (AAST grade III
V) blunt splenic trauma, following a standardized treatment protocol. METHODS:
All the hemodynamically stable patients with computer tomography (CT) diagnosis
of blunt splenic trauma underwent NOM, which included strict clinical and
laboratory observation, 48-72 h contrast-enhanced ultrasonography (CEUS) follow
up and splenic angioembolization, performed both in patients with admission CT
evidence of vascular injuries and in patients with falling hematocrit during
observation. RESULTS: 87 patients [32 (36.7 %) women and 55 (63.2 %) men, median
age 34 (range 14-68)] were included. Of these, 28 patients (32.1 %) had grade I,
22 patients (25.2 %) grade II, 20 patients (22.9 %) grade III, 11 patients (12.6
%) grade IV and 6 patients (6.8 %) grade V injuries. The overall success rate of
NOM was 95.4 % (82/87). There was no significant difference in the success rate
between the patients with different splenic injuries grade. Of 24 patients that
had undergone angioembolization, 22 (91.6 %) showed high splenic injury grade.
The success rate of embolization was 91.6 % (22/24). No major complications were
observed. The minor complications (2 pleural effusions, 1 pancreatic fistula and
2 splenic abscesses) were successfully treated by EAUS or CT guided drainage.
CONCLUSIONS: The non operative management of blunt splenic trauma, according to
our protocol, represents a safe and effective treatment for both minor and severe
injuries, achieving an overall success rate of 95 %. The angiographic study could
be indicated both in patients with CT evidence of vascular injuries and in
patients with high-grade splenic injuries, regardless of CT findings.
PMID- 26416402
TI - A small case series of aortic balloon occlusion in trauma: lessons learned from
its use in ruptured abdominal aortic aneurysms and a brief review.
AB - BACKGROUND: EndoVascular and Hybrid Trauma Management (EVTM) is an emerging
concept for the early treatment of trauma patients using aortic balloon occlusion
(ABO), embolization agents and stent grafts to stop ongoing traumatic bleeding.
These techniques have previously been implemented successfully in the treatment
of ruptured aortic aneurysm. AIMS: We describe our very recent experience of EVTM
using ABO in bleeding patients and lessons learned over the last 20 years from
the endovascular treatment of ruptured abdominal aortic aneurysms (rAAA). We also
briefly describe current knowledge of ABO usage in trauma. METHODS: A small
series of educational cases in our hospital is described, where endovascular
techniques were used to gain temporary hemorrhage control. The methods used for
rAAA and their applicability to EVTM with a multidisciplinary approach are
presented. RESULTS: Establishing femoral arterial access immediately on arrival
at the emergency room and use of an angiography table in the surgical suite may
facilitate EVTM at an early stage. ABO may be an effective method for the
temporary stabilization of severely hemodynamically unstable patients with
hemorrhagic shock, and may be useful as a bridge to definitive treatment of the
bleeding patients. CONCLUSION: EVTM, including the usage of ABO, can be initiated
on patient arrival and is feasible. Further data need to be collected to
investigate proper indications for ABO, best clinical usage, results and
potential complications. Accordingly, the ABOTrauma Registry has recently been
set up. Existing experiences of EVTM and lessons from the endovascular treatment
of rAAA may be useful in trauma management.
PMID- 26416403
TI - HFE p.C282Y gene variant is associated with varicose veins in Russian population.
AB - Recently, the association of polymorphism rs1800562 (p.C282Y) in the
hemochromatosis (HFE) gene with the increased risk of venous ulceration was
shown. We hypothesized that HFE gene polymorphism might be involved not only in
ulceration process, but also in susceptibility to primary varicose veins. We
genotyped HFE p.C282Y (rs1800562) and p.H63D (rs1799945) variants in patients
with primary varicose veins (n = 463) and in the control group (n = 754). In our
study, p.282Y variant (rs1800562 A allele) was significantly associated with the
risk of varicose veins (OR 1.79, 95 % CI = 1.11-2.89, P = 0.02). A borderline
significant reverse association of p.63D variant (rs1799945 G allele) with venous
leg ulcer development was revealed in Russians (OR 0.25, 95 % CI = 0.06-1.00, P =
0.05), but not in the meta-analysis (P = 0.56). We conclude that the HFE gene
polymorphism can affect the risk of developing primary varicose veins.
PMID- 26416405
TI - Longevity and aging. Mechanisms and perspectives.
AB - Longevity can mostly be determined with relative accuracy from birth and death
registers when available. Aging is a multifactorial process, much more difficult
to quantitate. Every measurable physiological function declines with specific
speeds over a wide range. The mechanisms involved are also different, genetic
factors are of importance for longevity determinations. The best-known genes
involved are the Sirtuins, active at the genetic and epigenetic level. Aging is
multifactorial, not "coded" in the genome. There are, however, a number of well
studied physical and biological parameters involved in aging, which can be
determined and quantitated. We shall try to identify parameters affecting
longevity as well as aging and suggest some reasonable predictions for the
future.
PMID- 26416404
TI - Increased inflammatory markers with altered antioxidant status persist after
clinical recovery from severe sepsis: a correlation with low HDL cholesterol and
albumin.
AB - Markers of oxidative stress and antioxidant status in relation to inflammatory
mediators in septic patients (SPs) during the course of sepsis and after recovery
were analysed. Patients were 30 critically ill adults in severe sepsis/septic
shock, 19 of which completed 3 samplings (S1: within 24 h after onset of sepsis,
S7: 7 days after S1, R7: 7 days after clinical recovery). Comparing SPs with
healthy controls (HCs), enhanced C-reactive protein, procalcitonin, bilirubin and
CuZn-superoxide dismutase activity were found at S1 only. Oxidized low-density
lipoprotein, conjugated dienes and nitrotyrosine were increased at S1, culminated
at S7 and reverted nearly to HC levels at R7. Reduced catalase activity and serum
amyloid were observed at S1 and endured until R7. Increase in IL-6, IL-10 and
tumour necrosis factor alpha (TNF-alpha) with accompanying decrease in
apolipoprotein A1, high-density lipoprotein (HDL) cholesterol, selenium, zinc,
albumin, paraoxonase 1 and glutathione peroxidase 1 activity appeared at S1 and
persisted until R7. TNF-alpha, IL-10 and markers of oxidative stress were in
negative correlation with HDL cholesterol and albumin at R7. After clinical
recovery, increased cytokines and decreased antioxidants were accompanied by
lower albumin and HDL cholesterol levels. During this important and beneficial
period of tissue repair, patients with prolonged persistence of this status are
probably more vulnerable to secondary infections and should be dealt with as
constituting a high-risk population.
PMID- 26416406
TI - Hypertrophic cardiomyopathy - Obstructive form as hematological disease, from
hemodynamic to hematologic abnormalities.
PMID- 26416408
TI - Isolation, Identification, and Autotoxicity Effect of Allelochemicals from
Rhizosphere Soils of Flue-Cured Tobacco.
AB - Autotoxicity, defined as a deleterious allelopathic effect among individuals of
the same plant species, is considered as one of the factors that contributes to
replant failure. Tobacco, as an important cultured and economic crop over the
world, has been often hampered by replant failure. In view of the seriousness of
this problem, the allelochemicals of flue-cured tobacco and their allelopathic
effects were investigated. The extracts of rhizosphere soil exhibited phytotoxic
activities against Lactuca sativa and autotoxic activities against tobacco
itself. Bioassay-guided fractionation of the extract led to the isolation of six
compounds, the structures of which were elucidated by spectroscopic analysis.
Among them, beta-cembrenediol (1), di-n-hexyl phthalate (2), and bis(2
propylheptyl) phthalate (3) showed observably phytotoxic activities against L.
sativa seedlings and autotoxic activities on tobacco. The allelochemicals were
then verified in the root zone soils of flue-cured tobacco by high-performance
liquid chromatography (HPLC). These results provide new insights into the
allelopathic mechanisms involved in the replant failure of flue-cured tobacco.
PMID- 26416407
TI - Trends in the incidences of acute myocardial infarction in coastal and inland
areas in Japan: The Yamagata AMI Registry.
AB - BACKGROUND: It has been reported that there are regional differences in the
incidence of acute myocardial infarction (AMI) in Japan. The purpose of this
study was to investigate trends in regional differences in AMI incidence and
dyslipidemia between coastal and inland areas. METHODS: We investigated trends in
AMI incidence and risk factors in 5325 first-ever AMI patients residing in a
coastal area (n=1817), a rural inland area (n=1959), or an urban inland area
(n=1549) for the periods 1994-2002, and 2003-2010, using data from the Yamagata
AMI Registry. RESULTS: Patients in the coastal area were significantly older than
those in rural and urban inland areas and had a lower prevalence of dyslipidemia.
The age-adjusted incidence rate of AMI was significantly lower in coastal and
rural inland areas patients than those from urban inland area (males: 43.3, 42.2,
and 51.3/10(5) person-years; females: 17.4, 20.0, and 23.7/10(5) person-years,
respectively) during 2 observation periods. Due to a large increase in AMI
incidence in younger males of the coastal area and a decrease in AMI incidence in
late elderly females of the urban inland area, no significant regional
differences in the age-adjusted incidence rates of AMI were observed during the
2003-2010 period in both genders. The increase in AMI incidence in males in the
coastal area was associated with an increasing prevalence of dyslipidemia.
CONCLUSION: There were no longer any regional differences observed in AMI
incidence, which was considered to be associated with increased dyslipidemia
especially in the coastal area.
PMID- 26416409
TI - Design of an internal amplification control for a duplex PCR used in the
detection of Shiga toxin producing Escherichia coli in pediatric feces.
AB - A conventional PCR targeted directly to the detection of Shiga toxin-producing
Escherichia coli (STEC) in diarrheal stools of symptomatic patients may require
the introduction of internal controls to detect false negative results. In the
present study, we designed a competitive internal amplification control (IAC) to
be included in a well-known PCR protocol used to amplify the stx1and stx2 genes
from STEC isolates. The IAC was introduced in the PCR reaction and amplified when
E. coli O157:H7 cultures and contaminated pediatric feces were assayed. When STEC
concentration was 10(3) CFU ml(-1) in pure culture and 10(4) CFU g(-1) in
contaminated stools, the IAC at concentration of 0.143 pg MUl(-1) in the PCR
reaction mixture was co-amplified with the stx2 sequence, producing bands of 279
and 349 bp, respectively. These STEC values were considered the detection limits
of the duplex PCR. The specific detection of STEC by duplex PCR including IAC
might be achieved directly on pediatric feces when the pathogen load reaches
concentrations of at least 10(4) CFU g(-1).
PMID- 26416410
TI - Going against the grain.
PMID- 26416411
TI - Defining the Impact of Surgical Approach on Perioperative Outcomes for Patients
with Gastric Cardia Malignancy.
AB - BACKGROUND: Gastric cardia cancer is currently treated with several operations.
The purpose of the current study was to compare outcomes associated with three
common operative approaches. METHODS: The ACS-NSQIP Participant Use File was
searched to identify all patients with gastric cardia malignancy who underwent
total gastrectomy (TG), transhiatal esophagectomy (THE), or thoraco-abdominal
esophagectomy (TAE) between 2005 and 2012. Demographic, perioperative risk
factors, and outcomes were analyzed. RESULTS: Overall, there were 982 patients
identified in the database who met inclusion criteria. The median age was 65
years (range 20-88) and 807 (82.2%) were male. The number of patients allocated
to each approach was 204 TGs (20.8%), 271 THE (27.6%), and 507 TAE (51.6%). All
approaches had similar major morbidity, cardiopulmonary morbidity, and 30-day
mortality, however, TAE was associated with the highest overall morbidity (TAE
49.9% vs. TG 40.7% and THE 43.5%, p = 0.048). The independent risk factors
predicting mortality were age greater than 65 years, history of myocardial
infarction, and postoperative cardiopulmonary morbidity. CONCLUSIONS: For
patients with proximal gastric cancer, the three most common operative approaches
were associated with clinically-significant rates of overall and major morbidity.
Approach-associated morbidity should be considered along with tumor location and
extent when choosing a technique for resection of gastric cardia malignancy.
PMID- 26416412
TI - High prevalence of colonization of oral cavity by respiratory pathogens in frail
older patients with oropharyngeal dysphagia.
AB - BACKGROUND: Aspiration pneumonia (AP) is caused by dysfunctional swallowing
resulting in aspiration of material colonized by respiratory pathogens. The aim
of this study was to assess and compare the swallowing physiology, health status,
oral health status, and oral/nasal microbiota in frail older patients (FOP) with
oropharyngeal dysphagia (OD) and a control group. METHODS: We studied 47 FOP (>70
year) with OD by videofluoroscopy (17 with acute pneumonia -APN-, 15 with prior
pneumonia-PNP- and 15 without) and 14 older controls without OD (H). Oral/nasal
colonization by five respiratory pathogens was evaluated by qPCR, whereas
commensal microbiota composition was assessed by pyrosequencing. KEY RESULTS: (i)
Frail older patients with OD presented similar comorbidities, poor functionality,
polymedication, and prevalent videofluoroscopic signs of impaired safety of
swallow (33.3-61.5%). However, patients with OD-APN also presented malnutrition,
delayed laryngeal vestibule closure (409.23 +/- 115.6 ms; p < 0.05), and silent
aspirations (15.6%). (ii) Oral health was poor in all groups, 90% presented
periodontitis and 72%, caries. (iii) Total bacterial load was similar in all
groups, but higher in the oropharynx (>10(8) CFU/mL) than in the nose (<10(6)
CFU/mL) (p < 0.0001). Colonization by respiratory pathogens was very high: 93% in
OD patients (p < 0.05 vs H); 93% in OD-PNP (p < 0.05 vs H); 88% in OD-APN (p =
0.07 vs H), and lower in controls (67%). CONCLUSIONS & INFERENCES: Frail older
patients with OD had impaired health status, poor oral health, high oral
bacterial load, and prevalence of oral colonization by respiratory pathogens and
VFS signs of impaired safety of swallow, and were therefore at risk for
contracting AP.
PMID- 26416413
TI - Multistep, effective drug distribution within solid tumors.
AB - The distribution of drugs within solid tumors presents a long-standing barrier
for efficient cancer therapies. Tumors are highly resistant to diffusion, and the
lack of blood and lymphatic flows suppresses convection. Prolonged, continuous
intratumoral drug delivery from a miniature drug source offers an alternative to
both systemic delivery and intratumoral injection. Presented here is a model of
drug distribution from such a source, in a multistep process. At delivery onset
the drug mainly affects the closest surroundings. Such 'priming' enables drug
penetration to successive cell layers. Tumor 'void volume' (volume not occupied
by cells) increases, facilitating lymphatic perfusion. The drug is then
transported by hydraulic convection downstream along interstitial fluid pressure
(IFP) gradients, away from the tumor core. After a week tumor cell death occurs
throughout the entire tumor and IFP gradients are flattened. Then, the drug is
transported mainly by 'mixing', powered by physiological bulk body movements.
Steady state is achieved and the drug covers the entire tumor over several
months. Supporting measurements are provided from the LODER system, releasing
siRNA against mutated KRAS over months in pancreatic cancer in-vivo models. LODER
was also successfully employed in a recent Phase 1/2 clinical trial with
pancreatic cancer patients.
PMID- 26416414
TI - Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon
11 mutated GIST: a retrospective analysis.
AB - We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who
received sunitinib or dose-escalated imatinib as second line.All patients
progressed on imatinib (400 mg/die) and received a second line treatment with
imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day).
Deletion versus other KIT 11 mutation was recorded, correlated with clinical
benefits.64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available
in 94 patients. With a median follow-up of 61 months, median time to progression
(TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7-10.9) and 5
months (95% CI 3.6-6.7) respectively (P = 0.012). No difference was found in
overall survival (OS) (P = 0.883). In imatinib arm, KIT exon 11 deletions was
associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54
vs 71 months P = 0.063). No difference was found in patients treated with
sunitinib (P = 0.370).A second line with sunitinib was associated with an
improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die.
Deletions in exon 11 seemed to be correlated with worse outcome in patients
receiving imatinib-based second line.
PMID- 26416415
TI - miR-134 in extracellular vesicles reduces triple-negative breast cancer
aggression and increases drug sensitivity.
AB - Exosomes (EVs) have relevance in cell-to-cell communication carrying pro
tumorigenic factors that participate in oncogenesis and drug resistance and are
proposed to have potential as self-delivery systems. Advancing on our studies of
EVs in triple-negative breast cancer, here we more comprehensively analysed
isogenic cell line variants and their EV populations, tissues cell line variants
and their EV populations, as well as breast tumour and normal tissues. Profiling
384 miRNAs showed EV miRNA content to be highly representative of their cells of
origin. miRNAs most substantially down-regulated in aggressive cells and their
EVs originated from 14q32. Analysis of miR-134, the most substantially down
regulated miRNA, supported its clinical relevance in breast tumours compared to
matched normal breast tissue. Functional studies indicated that miR-134 controls
STAT5B which, in turn, controls Hsp90. miR-134 delivered by direct transfection
into Hs578Ts(i)8 cells (in which it was greatly down-regulated) reduced STAT5B,
Hsp90, and Bcl-2 levels, reduced cellular proliferation, and enhanced cisplatin
induced apoptosis. Delivery via miR-134-enriched EVs also reduced STAT5B and
Hsp90, reduced cellular migration and invasion, and enhanced sensitivity to anti
Hsp90 drugs. While the differing effects achieved by transfection or EV delivery
are likely to be, at least partly, due to specific amounts of miR-134 delivered
by these routes, these EV-based studies identified miRNA-134 as a potential
biomarker and therapeutic for breast cancer.
PMID- 26416416
TI - TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q)
myelodysplastic syndromes.
AB - P53 is a key regulator of many cellular processes and is negatively regulated by
the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single
nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are
linked to cancer susceptibility, disease progression, and therapy response. We
analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to
outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was
performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP
scoring system ranging from +2 to -2 based on predicted p53 activity, we found
statistically significant differences in overall survival (OS) (p = 0.02) and
progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low
functional scores. In univariate analysis, only IPSS and the functional SNP score
predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the
functional SNP score was independent of IPSS for OS and PFS. These data
underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a
novel scoring system independent of IPSS that is predictive for disease outcome.
PMID- 26416417
TI - Phospho-ERK1/2 levels in cancer cell nuclei predict responsiveness to
radiochemotherapy of rectal adenocarcinoma.
AB - Locally advanced rectal adenocarcinoma is treated with radiochemotherapy (RCT)
before surgery. The response to RCT is heterogeneous and consensus regarding
reliable predictors is lacking. Since the ERK pathway is implicated in
radioprotection, we examined pretreatment biopsies from 52 patients by
immunohistochemistry for phosphorylated ERK (pERK). Immunostaining for pERK was
considerably enhanced by use of alkaline demasking. Nuclear staining occurred in
both cancer cells and stromal cells. Blind-coded sections were scored by 2
independent investigators. In patients showing no residual tumor after RCT
(TRG1), staining for pERK in cancer, but not stromal, cell nuclei was
significantly weaker than in patients showing a poor RCT response (TRG1 vs TRG4:
p = 0.0001). Nuclear staining for pERK predicted poor responders, as illustrated
by receiver operating characteristic curves with an area under curve of 0.86 (p =
0.0007) and also predicted downstaging (area under curve: 0.76; p = 0.01). A
number of controls documented the specificity of the optimized staining method
and results were confirmed with another pERK antibody. Thus, staining for pERK in
cancer cell nuclei can predict the response to RCT and may help spare poor
responders this treatment. These results also raise the question whether
inhibitors of ERK activation may serve as response modifiers of RCT.
PMID- 26416418
TI - The eye lens: age-related trends and individual variations in refractive index
and shape parameters.
AB - The eye lens grows throughout life by cell accrual on its surface and can change
shape to adjust the focussing power of the eye. Varying concentrations of
proteins in successive cell layers create a refractive index gradient. The
continued growth of the lens and age-related changes in proteins render it less
able to alter shape with loss of capacity by the end of the sixth decade of life.
Growth and protein ageing alter the refractive index but as accurate measurement
of this parameter is difficult, the nature of such alterations remains uncertain.
The most accurate method to date for measuring refractive index in intact lenses
has been developed at the SPring-8 synchrotron. The technique, based on Talbot
interferometry, has an X-ray source and was used to measure refractive index in
sixty-six human lenses, aged from 16 to 91 years. Height and width were measured
for forty-five lenses. Refractive index contours show decentration in some older
lenses but individual variations mask age-related trends. Refractive index
profiles along the optic axis have relatively flat central sections with distinct
micro-fluctuations and a steep gradient in the cortex but do not exhibit an age
related trend. The refractive index profiles in the equatorial aspect show
statistical significance with age, particularly for lenses below the age of sixty
that had capacity to alter shape in vivo. The maximum refractive index in the
lens centre decreases slightly with age with considerable scatter in the data and
there are age-related variations in sagittal thickness and equatorial height.
PMID- 26416419
TI - Antigen-specific human NKT cells from tuberculosis patients produce IL-21 to help
B cells for the production of immunoglobulins.
AB - Natural killer T (NKT) cells from mouse and human play an important role in the
immune responses against Mycobacterium tuberculosis. However, the function of
CD3(+)TCRvbeta11(+) NKT cells at the local site of M. tuberculosis infection
remains poorly defined. In the present study, we found that after stimulation
with M. tuberculosis antigens, NKT cells isolated from tuberculosis (TB) pleural
fluid mononuclear cells (PFMCs) produced IL-21 and other cytokines including IFN
gamma, TNF-alpha, IL-2 and IL-17. IL-21-expressing NKT cells in PFMCs displayed
effector memory phenotype, expressing CD45RO(high)CD62L(low)CCR7(low). Moreover,
NKT cells expressed high levels of CXCR5 and all of IL-21-expressing NKT cells co
expressed CXCR5. The frequency of BCL-6-expression was higher in IL-21-expressing
but not in non-IL-21-expressing CD3(+)TCRvbeta11(+) NKT cells. Sorted
CD3(+)TCRvbeta11(+) NKT cells from PFMCs produced IFN-gamma and IL-21 after
stimulation, which expressed CD40L. Importantly, CD3(+)TCRvbeta11(+) NKT cells
provided help to B cells for the production of IgG and IgA. Taken together, our
data demonstrate that CD3(+)TCRvbeta11(+) NKT cells from a local site of M.
tuberculosis infection produce IL-21, express CXCR5 and CD40L, help B cells to
secrete IgG and IgA, and may participate in local immune responses against M.
tuberculosis infection.
PMID- 26416420
TI - PDGF upregulates CLEC-2 to induce T regulatory cells.
AB - The effect of platelet derived growth factor (PDGF) on immune cells is not
elucidated. Here, we demonstrate PDGF inhibited the maturation of human DCs and
induced IL-10 secretion. Culture of PDGF-DCs with T cells induced the
polarization of T cells towards FoxP3 expressing T regulatory cells that secreted
IL-10. Gene expression studies revealed that PDGF induced the expression of C
type lectin like receptor member 2, (CLEC-2) receptor on DCs. Furthermore, DCs
transfected with CLEC-2 induced T regulatory cells in DC-T cell co-culture. CLEC
2 is naturally expressed on platelets. Therefore, to confirm whether CLEC-2 is
responsible for inducing the T regulatory cells, T cells were cultured with
either CLEC-2 expressing platelets or soluble CLEC-2. Both conditions resulted in
the induction of regulatory T cells. The generation of T regulatory cells was
probably due to the binding of CLEC-2 with its ligand podoplanin on T cells,
since crosslinking of podoplanin on the T cells also resulted in the induction of
T regulatory cells. These data demonstrate that PDGF upregulates the expression
of CLEC-2 on cells to induce T regulatory cells.
PMID- 26416421
TI - Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post
treatment variation compared to CA-125 and potential for prediction of
progression-free survival.
AB - Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated
four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as
candidate biomarkers. Using qPCR, we assessed the plasma concentration of these
markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy
women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa
patients, the assay was repeated at the end of the primary treatment. The pattern
of variations (post- minus pre-treatment) of concentration was compared to that
of CA-125. A Cox regression model was used to study the association between
variations and the progression-free survival (PFS). Plasma miR-200b proved to
have a greater average concentration in OvCa samples (median 2-DeltaDeltaCt =
15.18) than in samples linked to non-malignant lesions (median 2-DeltaDeltaCt =
1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa
patients, without any correlations with the FIGO stage and the pre-treatment CA
125 level. The decrease in CA-125 concentration was constant and often dramatic,
while the variations of miR-200b concentration were much more diverse. The
variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95
95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent
variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study
is the first direct empirical evidence that miR-200b can provide additional
information, independent of CA-125 in OvCa patients.
PMID- 26416422
TI - Kruppel-like factor 2 suppresses mammary carcinoma growth by regulating retinoic
acid signaling.
AB - The transcription factor Kruppel-like factor 2 (KLF2) displays anticarcinogenic
activities but the mechanism that underlies this activity is unknown. We show
here that KLF2 is markedly downregulated in human breast cancers and that its
expression positively correlates with breast cancer patient survival. We show
further that KLF2 suppresses tumor development by controlling the transcriptional
activity of the vitamin A metabolite retinoic acid (RA). RA regulates gene
transcription by activating two types of nuclear receptors: RA receptors (RARs),
which inhibit tumor development, and peroxisome proliferator-activated receptor
beta/delta (PPARbeta/delta), which promotes tumorigenesis. The partitioning of RA
between these receptors is regulated by two carrier proteins: cellular retinoic
acid-binding protein 2 (CRABP2), which delivers RA to RARs, and fatty acid
binding protein 5 (FABP5), which shuttles ligands to PPARbeta/delta. We show that
KLF2 induces the expression of CRABP2 and RARgamma and inhibits the expression
FABP5 and PPARbeta/delta thereby shifting RA signaling from the pro-carcinogenic
FABP5/PPARbeta/delta to the growth-suppressing CRABP2/RAR path. The data thus
reveal that KLF2 suppresses tumor growth by controlling the transcriptional
activities of RA.
PMID- 26416423
TI - Positron emission tomography imaging of cardiomyocyte apoptosis with a novel
molecule probe [18F]FP-DPAZn2.
AB - Cardiomyocyte apoptosis plays a causal role in the development and progression of
heart failure. Currently, there is no effective imaging agent that can be used to
detect cardiomyocyte apoptosis in vivo. To target phosphatidylserine (PS) on the
surface of the dying cell, we synthesized a novel 18F-labeled Zn2+-dipicolylamine
(DPA) analog, [18F]FP-DPAZn2, and evaluated it for noninvasive imaging of
cardiomyocyte apoptosis. In vitro, the fluorescence imaging of dansyl-DPAZn2 was
suitable for detecting cardiomyocyte apoptosis, which was confirmed by confocal
immunofluorescence imaging, terminal dUTP nick-end labeling (TUNEL) assay, and
western blot assay. The in vivo biodistribution showed that the uptake ratios of
[18F]FP-DPAZn2 in the heart were 4.41+/-0.29% ID/g at 5 min, 2.40 +/- 0.43% ID/g
at 30 min, 1.63 +/- 0.26% ID/g at 60 min, and 1.43% +/- 0.07 ID/g at 120 min post
injection. In vivo, the [18F]FP-DPAZn2 PET images showed more cardiac
accumulation of radioactivity 60 min post-injection in acute myocardial
infarction (AMI) rats than in normal rats, which was consistent with the findings
of a histological analysis of the rat cardiac tissues in vitro. [18F]FP-DPAZn2
PET imaging has the capability for myocardial apoptosis detection, but the method
will require improved myocardial uptake for the noninvasive evaluation of
cardiomyocyte apoptosis in clinical settings.
PMID- 26416424
TI - Loss of p27Kip1 promotes metaplasia in the pancreas via the regulation of Sox9
expression.
AB - p27Kip1 (p27) is a negative regulator of proliferation and a tumor suppressor via
the inhibition of cyclin-CDK activity in the nucleus. p27 is also involved in the
regulation of other cellular processes, including transcription by acting as a
transcriptional co-repressor. Loss of p27 expression is frequently observed in
pancreatic adenocarcinomas in human and is associated with decreased patient
survival. Similarly, in a mouse model of K-Ras-driven pancreatic cancer, loss of
p27 accelerates tumor development and shortens survival, suggesting an important
role for p27 in pancreatic tumorigenesis. Here, we sought to determine how p27
might contribute to early events leading to tumor development in the pancreas. We
found that K-Ras activation in the pancreas causes p27 mislocalization at pre
neoplastic stages. Moreover, loss of p27 or expression of a mutant p27 that does
not bind cyclin-CDKs causes the mislocalization of several acinar polarity
markers associated with metaplasia and induces the nuclear expression of Sox9 and
Pdx1 two transcription factors involved in acinar-to-ductal metaplasia. Finally,
we found that p27 directly represses transcription of Sox9, but not that of Pdx1.
Thus, our results suggest that K-Ras activation, the earliest known event in
pancreatic carcinogenesis, may cause loss of nuclear p27 expression which results
in derepression of Sox9, triggering reprogramming of acinar cells and metaplasia.
PMID- 26416426
TI - Hippo transducer TAZ promotes epithelial mesenchymal transition and supports
pancreatic cancer progression.
AB - Transcriptional co-activator with PDZ binding motif (TAZ) is a transducer of the
Hippo pathway and promotes cancer development and progression. In the present
study, we sought to determine the roles and underlying mechanisms of elevated
expression and activation of TAZ in pancreatic cancer development and
progression. The mechanistic role of TAZ and Hippo signaling in promotion of
pancreatic cancer development and progression was examined using cell culture,
molecular biology, and mouse models. The relevance of our experimental and
mechanistic findings was validated using human pancreatic tumor specimens. We
found that TAZ expression was markedly higher in pancreatic tumors than in normal
pancreatic tissue. Further analysis of the correlation of TAZ expression with
tissue microarray clinicopathologic parameters revealed that this expression was
positively associated with tumor differentiation. Also, TAZ expression was higher
in pancreatic cancer cell lines than in pancreatic ductal epithelial cells. TAZ
activation in pancreatic cancer cells promoted their proliferation, migration,
invasion, and epithelial-mesenchymal transition. Further mechanistic studies
demonstrated that aberrant expression and activation of TAZ in pancreatic cancer
cells resulted from suppression of the expression of Merlin, a positive regulator
upstream of the Hippo pathway, and that the oncogenic function of TAZ in
pancreatic cancer cells was mediated by TEA/ATTS domain transcription factors.
Therefore, TAZ functioned as an oncogene and promoted pancreatic cancer
epithelial-mesenchymal transition and progression. TAZ thus may be a target for
effective therapeutic strategies for pancreatic cancer.
PMID- 26416425
TI - Frequent DPH3 promoter mutations in skin cancers.
AB - Recent reports suggested frequent occurrence of cancer associated somatic
mutations within regulatory elements of the genome. Based on initial exome
sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers
in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and
oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature
mutations occurred at sites adjacent and within a binding motif for E-twenty
six/ternary complex factors (Ets/TCF), at -8 and -9 bp from DPH3 transcription
start site. Follow up screening of 586 different skin lesions showed that the
DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma
(30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell
carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma
cell line for DPH3 and OXNAD1 orientations showed statistically significant
increased promoter activity due to -8/-9CC > TT tandem mutations; although, no
effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed.
The results from this study show occurrence of frequent somatic non-coding
mutations adjacent to a pre-existing binding site for Ets transcription factors
within the directional promoter of DPH3 and OXNAD1 genes in three major skin
cancers. The detected mutations displayed typical UV signature; however, the
functionality of the mutations remains to be determined.
PMID- 26416429
TI - Cross cultural adaptation of the English version of the IOF-QLQ to Polish, to
assess the health-related quality-of-life of patients after a distal radius
fracture.
AB - BACKGROUND: A distal radius fracture (DRF) is a common injury that can cause
significant pain and lead to a prolonged decrease in physical, emotional, and
social functioning. In modern randomized clinical trials, assessing outcomes
after a DRF, health-related quality-of-life (HRQoL) is a "must-be" endpoint.
Additionally, HRQoL assessments are essential in the clinical decision-making
process. The aim of this study to cross-culturally adapt the International
Osteoporosis Foundation Quality of Life Questionnaire (IOF QLQ) for patients with
a DRF to Polish. METHODS: A standard forward-backward translation procedure and
pilot-testing were used to prepare the Polish version of the IOF QLQ for use in
this case-control study. Patients were eligible if they were between 18-80 years
and were within 1-3 days after a non-comminuted DRF. The study group was gender
and aged matched with healthy controls. All DRF patients filled out the Polish
version of the IOF QLQ, the SF-36 and a demographic questionnaire. Assessment
points were set as soon as possible after the fracture, 7 days, 6 weeks, 3, 6,
12, and 18 months after the fracture. Standard validity and reliability analyses
were performed. RESULTS: Ninety-seven patients (73 women - 75.3%) with a mean age
of 62.4 +/- 7.1 years agreed to take part in the study. The control group
consisted of 81 patients (60 women - 74.1%) with a mean age 63.9 +/- 8.2 years.
No significant differences were found between the mean age of patients and
controls (p = 0.19). Cronbach's alpha coefficients showed positive internal
consistency (0.79-0.89). The interclass correlations for the IOF QLQ domains and
the overall score ranged from 0.85 to 0.92. Satisfactory convergent and
discriminant validity of the IOF QLQ was seen. CONCLUSIONS: The Polish version of
the IOF QLQ for patients with a DRF is a reliable and valid tool for measuring
HRQoL. It can be fully recommended for use in clinical settings in the Polish
population. When combined with the SF-36 the IOF QLQ allows to obtain a
comprehensive HRQoL assessment in patients with a DRF.
PMID- 26416428
TI - Effects of normobaric oxygen and melatonin on reperfusion injury: role of
cerebral microcirculation.
AB - In order to protect the brain before an irreversible injury occurs, penumbral
oxygenation is the primary goal of current acute ischemic stroke treatment.
However, hyperoxia treatment remains controversial due to the risk of free
radical generation and vasoconstriction. Melatonin is a highly potent free
radical scavenger that protects against ischemic stroke. Considering its anti
oxidant activity, we hypothesized that melatonin may augment the survival
promoting action of normobaric oxygen (NBO) and prevent brain infarction. Herein,
we exposed mice to 30 or 90 min of intraluminal middle cerebral artery occlusion
(MCAo) and evaluated the effects of NBO (70% or 100% over 90 min), administered
either alone or in combination with melatonin (4 mg/kg, i.p.), on disseminate
neuronal injury, neurological deficits, infarct volume, blood-brain barrier (BBB)
permeability, cerebral blood flow (CBF) and cell signaling. Both NBO and
particularly melatonin alone reduced neuronal injury, neurological deficits,
infarct volume and BBB permeability, and increased post-ischemic CBF, evaluated
by laser speckle imaging (LSI). They also improved CBF significantly in the
ischemic- core and penumbra, which was associated with reduced IgG extravasation,
DNA fragmentation, infarct volume, brain swelling and neurological scores. Levels
of phosphorylated Akt, anti-apoptotic Bcl-xL, pro-apoptotic Bax and endothelial
nitric oxide synthase (NOS) were re-regulated after combined oxygen and melatonin
delivery, whereas neuronal and inducible NOS, which were increased by oxygen
treatment, were not influenced by melatonin. Our present data suggest that
melatonin and NBO are promising approaches for the treatment of acute-ischemic
stroke, which encourage proof-of-concept studies in human stroke patients.
PMID- 26416430
TI - 'We usually just start dancing our Indian dances': urban American Indian (AI)
female youths' negotiation of identity, health and the body.
AB - In this article, we utilise qualitative research techniques to explore how 14
urban American Indian (AI) females (aged 11-17) living in the state of Maryland
discursively construct and experience health and the body, as well as how/if
traditional culture shapes their understandings. In doing so, we address a
significant gap in the knowledge base concerning the health beliefs of urban AI
youth, and build upon research utilising a decolonising approach. Using a two
step process of thematic analysis and poststructuralist discourse analysis, we
arrived at three key findings: (1) while youths are taught (and learn) mainstream
lessons about health and bodily norms (mostly at school), they negotiate these
lessons in complex and at times contradictory ways; (2) they do not view their AI
status as conferring more or less risk upon them or their community; and (3) AI
identity appears to be fluid in nature, becoming more salient, even a resource,
in certain situations. We conclude with a discussion of the importance of spaces
within the urban context in shaping youths' embodied subjectivities, and in
particular, contrast the space of the school with that of the urban AI community
centre.
PMID- 26416427
TI - MYC-driven aggressive B-cell lymphomas: biology, entity, differential diagnosis
and clinical management.
AB - MYC, a potent oncogene located at chromosome locus 8q24.21, was identified
initially by its involvement in Burkitt lymphoma with t(8;14)(q24;q32). MYC
encodes a helix-loop-helix transcription factor that accentuates many cellular
functions including proliferation, growth and apoptosis. MYC alterations also
have been identified in other mature B-cell neoplasms and are associated with
aggressive clinical behavior. There are several regulatory factors and
dysregulated signaling that lead to MYC up-regulation in B-cell lymphomas. One
typical example is the failure of physiological repressors such as Bcl6 or BLIMP1
to suppress MYC over-expression. In addition, MYC alterations are often developed
concurrently with other genetic alterations that counteract the proapoptotic
function of MYC. In this review, we discuss the physiologic function of MYC and
the role that MYC likely plays in the pathogenesis of B-cell lymphomas. We also
summarize the role MYC plays in the diagnosis, prognostication and various
strategies to detect MYC rearrangement and expression.
PMID- 26416432
TI - EDUCATION AND IMAGING. Hepatobiliary and Pancreatic: Rapid growing cystic ovarian
metastasis from pancreatic cancer.
AB - Pancreatic cancer rarely develops cystic ovarian metastasis. We present a 63-year
old female patient with unresectable pancreas head cancer. Seven months after the
introduction of the chemoradiotherapy, a giant intrapelvic cystic tumor with
rapid growth was found. The tumor was resected because the patient complained of
severe bloating and no other new metastatic sites could be identified.
Postoperative pathological examination diagnosed it as an ovarian metastasis from
the pancreas cancer.
PMID- 26416431
TI - Anticancer Platelet-Mimicking Nanovehicles.
AB - A core-shell nanovehicle coated with a platelet membrane (PM) is developed for
targeted and site-specific delivery of an extracellularly active drug and an
intracellular functional small-molecular drug, leading to enhanced antitumor
efficacy. This PM-coated nanovehicle can also effectively eliminate the
circulating tumor cells in vivo and inhibit development of tumor metastasis.
PMID- 26416433
TI - The pathogenesis of Prurigo nodularis--'Super-Itch' in exploration.
AB - Prurigo nodularis (PN) is characterized by multiple hyperkeratotic nodules,
papules and the presence of intensive pruritus. This leads to an impaired quality
of life and high burden due not only to the severe itch but also the chronic,
skin lesions and lack of treatment options. The pathogenesis of PN is not
completely clarified. Previous studies have demonstrated just how important the
interaction between cutaneous nerve fibres and immune cells is. Besides a reduced
intraepidermal nerve fibre density, there are increased dermal levels of
neuropeptides such as substance P, calcitonin gene-related peptide and nerve
growth factor, as well as a predominant presence of eosinophils and mast cells.
An interaction of these factors results in a complex relationship which will be
discussed in this article.
PMID- 26416434
TI - Vacuum-and-solvent-free fabrication of organic semiconductor layers for field
effect transistors.
AB - We demonstrate that cold and hot isostatic pressing (CIP and HIP) is a novel,
alternative method for organic semiconductor layer fabrication, where organic
powder is compressed into a layer shape directly on a substrate with 200 MPa
pressure. Spatial gaps between powder particles and the other particles,
substrates, or electrodes are crushed after CIP and HIP, making it possible to
operate organic field-effect transistors (OFETs) containing the compressed powder
as the semiconductor. The CIP-compressed powder of 2,7-dioctyl[1]benzothieno[3,2
b][1]benzothiophene (C8-BTBT) had a hole mobility of (1.6 +/- 0.4) * 10(-2)
cm(2)/Vs. HIP of C8-BTBT powder increased the hole mobility to an amorphous
silicon-like value (0.22 +/- 0.07 cm(2)/Vs) because of the growth of the C8-BTBT
crystallites and the improved continuity between the powder particles. The vacuum
and solution processes are not involved in our CIP and HIP techniques, offering a
possibility of manufacturing OFETs at low cost.
PMID- 26416435
TI - Ultrafast Heme Dynamics of Ferric Cytochrome c in Different Environments:
Electronic, Vibrational, and Conformational Relaxation.
AB - The excited-state dynamics of ferric cytochrome c (Cyt c), an important electron
transfer heme protein, in acidic to alkaline medium and in its unfolded form are
investigated by using femtosecond pump-probe spectroscopy, exciting the heme and
Tryptophan (Trp) to understand the electronic, vibrational, and conformational
relaxation of the heme. At 390 nm excitation, the electronic relaxation of heme
is found to be ~150 fs at different pH values, increasing to 480 fs in the
unfolded form. Multistep vibrational relaxation dynamics of the heme, including
fast and slow processes, are observed at pH 7. However, in the unfolded form and
at pH 2 and 11, fast phases of vibrational relaxation dominate, revealing the
energy dissipation occurring through the covalent bond interaction between the
heme and the nearest amino acids. A significant shortening of the excited-state
lifetime of Trp is observed at various pH values at 280 nm excitation due to
resonance energy transfer to the heme. The longer time constant (25 ps) observed
in the unfolded form is attributed to a complete global conformational relaxation
of Cyt c.
PMID- 26416436
TI - Intersubject and Interday Variability in Human Tear and Meibum Lipidomes: A Pilot
Study.
AB - PURPOSE: Our aim was to quantitate day-to-day changes in the tear and meibum
lipid profile of individual subjects in a pilot study of healthy humans. METHODS:
Matched tear and meibum samples were obtained from four subjects on three
consecutive days. Quantitative lipid profiles of human basal tears and meibum
were compared using multivariate analysis by principal components. RESULTS:
Substantial differences in the lipid profile between subjects were observed,
while lipid profiles were steady across the three consecutive days of sampling.
Multivariate principal component analysis demonstrated that
lysophosphatidylcholine was the largest variant lipid class between subjects in
tears, while wax esters comprised the most variation between subjects in meibum
secretions. CONCLUSION: Interday variability is shown to be much smaller than
interpatient variability, suggesting that tears and meibum subjects both have
unique profiles in humans.
PMID- 26416437
TI - Medical Racism.
PMID- 26416439
TI - Enforcing the International Code of Marketing of Breast-milk Substitutes for
Better Promotion of Exclusive Breastfeeding: Can Lessons Be Learned?
AB - Exclusive breastfeeding, one of the best natural resources, needs protection and
promotion. The International Code of Marketing of Breast-milk Substitutes (the
Code), which aims to prevent the undermining of breastfeeding by formula
advertising, faces implementation challenges. We reviewed frequently overlooked
challenges and obstacles that the Code is facing worldwide, but particularly in
Southeast Asia. Drawing lessons from various countries where we work, and
following the example of successful public health interventions, we discussed
legislation, enforcement, and experiences that are needed to successfully
implement the Code. Successful holistic approaches that have strengthened the
Code need to be scaled up. Community-based actions and peer-to-peer promotions
have proved successful. Legislation without stringent enforcement and sufficient
penalties is ineffective. The public needs education about the benefits and ways
and means to support breastfeeding. It is crucial to combine strong political
commitment and leadership with strict national regulations, definitions, and
enforcement. National breastfeeding committees, with the authority to improve
regulations, investigate violations, and enforce the laws, must be established.
Systematic monitoring and reporting are needed to identify companies,
individuals, intermediaries, and practices that infringe on the Code. Penalizing
violators is crucial. Managers of multinational companies must be held
accountable for international violations, and international legislative
enforcement needs to be established. Further measures should include improved
regulations to protect the breastfeeding mother: large-scale education campaigns;
strong penalties for Code violators; exclusion of the formula industry from
nutrition, education, and policy roles; supportive legal networks; and
independent research of interventions supporting breastfeeding.
PMID- 26416438
TI - Human scaphoid non-unions exhibit increased osteoclast activity compared to
adjacent cancellous bone.
AB - Scaphoid bones have a high prevalence for non-union. Even with adequate
treatment, bone regeneration may not occur in certain instances. Although this
condition is well described, the molecular pathology of scaphoid non-unions is
still poorly defined. In this study, gene expression of osteogenic and angiogenic
growth and transcription factors as well as inflammatory mediators were analysed
in human scaphoid non-unions and intraindividually compared to adjacent
autologous cancellous bone from the distal radius. In addition, histology and
immunohistochemical stainings were performed to verify qRT-PCR data. Gene
expression analysis revealed a significant up-regulation of RANKL, ALP, CYCLIN
D1, MMP-13, OPG, NFATc1, TGF-beta and WNT5A in scaphoid non-unions.
Interestingly, RANKL and NFATc1, both markers for osteoclastogenesis, were
significantly induced in non-unions. Moreover, WNT5A was highly up-regulated in
all non-union samples. TRAP staining confirmed the observation of induced
osteoclastogenesis in non-unions. With respect to genes related to osteogenesis,
alkaline phosphatase was significantly up-regulated in scaphoid non-unions. No
differences were detectable for other osteogenic genes such as RUNX-2 or BMP-2.
Importantly, we did not detect differences in angiogenesis between scaphoid non
unions and controls in both gene expression and immunohistochemistry. Summarized,
our data indicate increased osteoclast activity in scaphoid non-unions possibly
as a result of the alterations in RANKL, TGF-beta and WNT5A expression levels.
These data increase our understanding for the reduced bone regeneration capacity
present in scaphoid non-unions and may translate into the identification of new
therapeutic targets to avoid secondary damages and prevent occurrence of non
unions to scaphoid bones.
PMID- 26416440
TI - Feeding Mode of Australian Infants in the First 12 Months of Life.
AB - BACKGROUND: In 2011, Australia published a set of 6 population-level indicators
assessing breastfeeding, formula use, and the introduction of
soft/semisolid/solid foods. OBJECTIVES: This study aimed to report the feeding
practices of Australian infants against these indicators and determine the
predictors of early breastfeeding cessation and introduction of solids. METHODS:
Mother-infant dyads (N = 1470) were recruited postnatally in 2 Australian capital
cities and regional areas of 1 state between February 2008 and March 2009.
Demographic and feeding intention data were collected by self-completed
questionnaire at infant birth, with feeding practices (current feeding mode, age
of breastfeeding cessation, age of formula and/or solids introduction) reported
when the infant was between 4 and 7 months of age, and around 13 months of age.
Multiple logistic regression was used to determine the predictors of
breastfeeding cessation and solids introduction. RESULTS: Although initiation of
breastfeeding was almost universal (93.3%), less than half of the infants were
breastfed to 6 months (41.7%) and 33.3% were receiving solids by 4 months. Women
who were socially disadvantaged, younger, less educated, unpartnered,
primiparous, and/or overweight were most likely to have ceased breastfeeding
before 6 months of age, and younger and/or less educated women were most likely
to have introduced solid food by 4 months of age. Not producing adequate milk was
the most common reason provided for cessation of breastfeeding. CONCLUSION: The
feeding behaviors of Australian infants in the first 12 months fall well short of
recommendations. Women need anticipatory guidance as to the indicators of
breastfeeding success and the tendency of women to doubt the adequacy of their
breast milk supply warrants further investigation.
PMID- 26416441
TI - The MCCB impairment profile in a Spanish sample of patients with schizophrenia:
Effects of diagnosis, age, and gender on cognitive functioning.
AB - The MATRICS Consensus Cognitive Battery (MCCB) was administered to 293
schizophrenia outpatients and 210 community residents in Spain. Our first
objective was to identify the age- and gender-corrected MCCB cognitive profile of
patients with schizophrenia. The profile of schizophrenia patients showed
deficits when compared to controls across the seven MCCB domains. Reasoning and
Problem Solving and Social Cognition were the least impaired, while Visual
Learning and Verbal Learning showed the greatest deficits. Our second objective
was to study the effects on cognitive functioning of age and gender, in addition
to diagnosis. Diagnosis was found to have the greatest effect on cognition
(Cohen's d>0.8 for all MCCB domains); age and gender also had effects on
cognitive functioning, although to a lesser degree (with age usually having
slightly larger effects than gender). The effects of age were apparent in all
domains (with better performance in younger subjects), except for Social
Cognition. Gender had effects on Attention/Vigilance, Working Memory, Reasoning
and Problem Solving (better performance in males), and Social Cognition (better
performance in females). No interaction effects were found between diagnosis and
age, or between diagnosis and gender. This lack of interactions suggests that age
and gender effects are not different in patients and controls.
PMID- 26416442
TI - Cognitive course in first-episode psychosis and clinical correlates: A 4 year
longitudinal study using the MATRICS Consensus Cognitive Battery.
AB - While cognitive impairments are prevalent in first-episode psychosis, the course
of these deficits is not fully understood. Most deficits appear to remain stable,
however there is uncertainty regarding the trajectory of specific cognitive
domains after illness onset. This study investigates the longitudinal course of
cognitive deficits four years after a first-episode of psychosis and the
relationship of performance with clinical course and response to treatment.
Twenty three individuals with psychotic illness, matched with 21 healthy
volunteers, were assessed using the MATRICS Consensus Cognitive Battery at
illness onset and 4 years later. We also investigated the relationship between
cognitive deficits and quality of life and clinical indices. Verbal learning and
two measures of processing speed had marked poorer trajectory over four years
compared to the remaining cognitive domains. Processing speed performance was
found to contribute to the cognitive deficits in psychosis. Poorer clinical
outcome was associated with greater deficits at illness onset in reasoning and
problem solving and social cognition. Cognitive deficits did not predict quality
of life at follow-up, nor did diagnosis subtype differentiate cognitive
performance. In conclusion, an initial psychotic episode may be associated with
an additional cost on verbal learning and two measures of processing speed over a
time spanning at least four years. Moreover, processing speed, which has been
manipulated through intervention in previous studies, may represent a viable
therapeutic target. Finally, cognition at illness onset may have a predictive
capability of illness course.
PMID- 26416443
TI - Prevalence and correlates of psychotic like experiences in a nationally
representative community sample of adolescents in Ireland.
AB - Adolescent psychotic like experiences (PLEs) are an important area of research,
yet only a small number of community surveys have investigated their psychosocial
correlates. This study presents the prevalence and correlates of three types of
PLEs in a nationally representative community sample of 12-19 year olds in
Ireland (N=5910). Correlates are considered across five domains: demographic,
stressful life experiences, emotional/behavioral problems, substance use, and
personal resources. Auditory hallucinations were reported by 13.7% of
participants, 10.4% reported visual hallucinations and 13.1% reported paranoid
thoughts. Participants who had experienced two of the three PLEs were assigned
"risk" status (10.4%; n=616). Using binary logistic regression, PLEs were
associated with a range of correlates across the five domains. Key correlates of
risk status include depression (OR 4.07; 95% CI 3.39-4.88), low self-esteem (OR
4.03 95% CI 3.34-4.86), low optimism (OR 3.56; 95% CI 2.96-4.28), school
misconduct (OR 3.10 95%; CI 2.56-3.75), and high avoidance coping (OR 2.86 95% CI
2.34-3.49). These associations remained significant in a multivariate analysis.
While correlates for each of the three PLEs were similar, there were some nuances
in these patterns. Notably, demographic and substance use variables were the
weakest groups of correlates. Personal resources (e.g. self-esteem, optimism and
coping) have been poorly studied in the adolescent PLE literature and these
findings provide important insights for future research and intervention design.
PMID- 26416445
TI - FXR induces SOCS3 and suppresses hepatocellular carcinoma.
AB - Suppressor of cytokine signaling 3 (SOCS3) is regarded as a vital repressor in
the liver carcinogenesis mainly by inhibiting signal transducer and activator of
transcription 3 (STAT3) activity. Farnesoid X Receptor (FXR), highly expressed in
liver, has an important role in protecting against hepatocellular carcinoma
(HCC). However, it is unclear whether the tumor suppressive activity of FXR
involves the regulation of SOCS3. In the present study, we found that activation
of FXR by its specific agonist GW4064 in HCC cells inhibited cell growth, induced
cell cycle arrest at G1 phase, elevated p21 expression and repressed STAT3
activity. The above anti-tumor effects of FXR were dramatically alleviated by
knockdown of SOCS3 with siRNA. Reporter assay revealed that FXR activation
enhanced the transcriptional activity of SOCS3 promoter. Electrophoretic mobility
shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay displayed that
FXR directly bound to IR9 DNA motif within SOCS3 promoter region. The in vivo
study in nude mice showed that treatment with FXR ligand GW4064 could decelerate
the growth of HCC xenografts, up-regulate SOCS3 and p21 expression and inhibit
STAT3 phosphorylation in the xenografts. These results suggest that induction of
SOCS3 may be a novel mechanism by which FXR exerts its anti-HCC effects, and the
FXR-SOCS3 signaling may serve as a new potential target for the
prevention/treatment of HCC.
PMID- 26416444
TI - Homozygous mdm2 SNP309 cancer cells with compromised transcriptional elongation
at p53 target genes are sensitive to induction of p53-independent cell death.
AB - A single nucleotide polymorphism (T to G) in the mdm2 P2 promoter, mdm2 SNP309,
leads to MDM2 overexpression promoting chemotherapy resistant cancers. Two mdm2
G/G SNP309 cancer cell lines, MANCA and A875, have compromised wild-type p53 that
co-localizes with MDM2 on chromatin. We hypothesized that MDM2 in these cells
inhibited transcription initiation at the p53 target genes p21 and puma.
Surprisingly, following etoposide treatment transcription initiation occurred at
the compromised target genes in MANCA and A875 cells similar to the T/T ML-1 cell
line. In all cell lines tested there was equally robust recruitment of total and
initiated RNA polymerase II (Pol II). We found that knockdown of MDM2 in G/G
cells moderately increased expression of subsets of p53 target genes without
increasing p53 stability. Importantly, etoposide and actinomycin D treatments
increased histone H3K36 trimethylation in T/T, but not G/G cells, suggesting a
G/G correlated inhibition of transcription elongation. We therefore tested a
chemotherapeutic agent (8-amino-adenosine) that induces p53-independent cell
death for higher clinically relevant cytotoxicity. We demonstrated that T/T and
G/G mdm2 SNP309 cells were equally sensitive to 8-amino-adenosine induced cell
death. In conclusion for cancer cells overexpressing MDM2, targeting MDM2 may be
less effective than inducing p53-independent cell death.
PMID- 26416447
TI - Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling
for hepatocellular carcinoma progression.
AB - One of the signaling components involved in hepatocellular carcinoma (HCC)
progression is the focal adhesion adaptor paxillin. Hydrogen peroxide inducible
clone-5 (Hic-5), one of the paralogs of paxillin, exhibits many biological
functions distinct from paxillin, but may cooperate with paxillin to trigger
tumor progression. Screening of Hic-5 in 145 surgical HCCs demonstrated
overexpression of Hic-5 correlated well with intra- and extra-hepatic metastasis.
Hic-5 highly expressed in the patient derived HCCs with high motility such as
HCC329 and HCC353 but not in the HCCs with low motility such as HCC340. Blockade
of Hic-5 expression prevented constitutive migration of HCC329 and HCC353 and HGF
induced cell migration of HCC340. HCC329Hic-5(-), HCC353Hic-5(-), HCC372Hic-5(-),
the HCCs stably depleted of Hic-5, exhibited reduced motility compared with each
HCC expressing Scramble shRNA. Moreover, intra/extrahepatic metastasis of
HCC329Hic-5(-) in SCID mice greatly decreased compared with HCC329Scramble. On
the other hand, ectopic Hic-5 expression in HCC340 promoted its progression.
Constitutive and HGF-induced Hic-5 expression in HCCs were suppressed by the
reactive oxygen species (ROS) scavengers catalase and dithiotheritol and c-Jun N
terminal kinase (JNK) inhibitor SP600125. On the contrary, depletion of Hic-5
blocked constitutive and HGF-induced ROS generation and JNK phosphorylation in
HCCs. Also, ectopic expression of Hic-5 enhanced ROS generation and JNK
phosphorylation. These highlighted that Hic-5 plays a central role in the
positive feedback ROS-JNK signal cascade. Finally, the Chinese herbal derived
anti-HCC peptide LZ-8 suppressed constitutive Hic-5 expression and JNK
phosphorylation. In conclusion, Hic-5 mediates ROS-JNK signaling and may serve as
a therapeutic target for prevention of HCC progression.
PMID- 26416446
TI - Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically
recognizes its aberrantly localized antigen in ovarian cancer cells and that is
suitable for selective drug delivery.
AB - Membrane protein claudin3 has been recently suggested as a marker for
biologically aggressive tumors and a possible target for the therapeutic delivery
of active anti-cancer compounds. Claudin3-binding molecules such as the
Clostridium perfringens enterotoxin (CPE), CPE-related molecules, and murine and
chimeric antibodies have shown promising antitumor efficacy in preclinical
oncological settings. We first engineered a fully human anti-claudin3 IgG1
antibody (IgGH6) by fusing the human IgG1 Fc-domain to the anti-claudin3 scFvH6
previously isolated from a pre-immune phage display library. The construct was
expressed in mammalian cells and specifically targeted claudin3 endogenously
expressed on the surface of different human ovarian cancer cell lines. No
detectable cross-reactivity with other homologous claudins was observed. The
epitope recognized by IgGH6 is located within the minor extracellular domain of
claudin3 and becomes accessible only in tumor cells characterized by incomplete
junction formation. Confocal microscopy experiments demonstrated that IgGH6 was
actively internalized in tumor cells after binding to native claudin3 and co
localized, likely within intracellular vesicles, with the C-CPE peptide.
Preliminary results indicate that IgGH6 accumulated in vivo in free claudin3
ovarian carcinoma xenografts. For its selective uptake in tumor cells and its
human nature, IgGH6 represents a valuable candidate for antibody-drug conjugate
therapeutic applications in ovarian cancer patients.
PMID- 26416448
TI - MicroRNAs as prognostic molecular signatures in renal cell carcinoma: a
systematic review and meta-analysis.
AB - This is a systematic review of studies investigating the prognostic value of
different microRNAs (miRs) in renal cell carcinoma (RCC). Twenty-seven relevant
studies were identified, with a total of 2578 subjects. We found that elevated
expression of miR-21, miR-1260b, miR-210, miR-100, miR-125b, miR-221, miR-630,
and miR-497 was associated with a poor prognosis in RCC patients. Conversely,
decreased expression of miR-106b, miR-99a, miR-1826, miR-215, miR-217, miR-187,
miR-129-3p, miR-23b, miR-27b, and miR-126 was associated with a worse prognosis.
We performed meta-analyses on studies to address the prognostic value of miR-21,
miR-126, miR-210, and miR-221. This revealed that elevated miR-21 expression was
associated with shorter overall survival (OS; hazard ratio [HR], 2.29; 95%
confidence interval [CI], 1.28-4.08), cancer specific survival (CSS; HR, 4.16;
95% CI, 2.49-6.95), and disease free survival (DFS; HR, 2.15; 95% CI, 1.16-3.98).
The decreased expression of miR-126 was associated with shorter CSS (HR, 0.35;
95% CI, 0.15-0.85), OS (HR, 0.45; 95% CI, 0.30-0.69), and DFS (HR 0.30; 95% CI,
0.18-0.50). Our comprehensive systematic review reveals that miRs, especially miR
21 and miR-126, could be promising prognostic markers and useful therapeutic
targets in RCC.
PMID- 26416449
TI - CCL18 from tumor-associated macrophages promotes angiogenesis in breast cancer.
AB - The infiltration of tumor-associated macrophages (TAMs) is associated with
extensive angiogenesis, which contributes to a poor prognosis in breast cancer.
However, anti-angiogenic therapy with VEGF-specific monotherapy has been
unsuccessful in treating breast cancer, and the molecular mechanisms associated
with chemoresistance remain unclear. Here, we investigated whether CCL18, a
chemokine produced by TAMs, can stimulate angiogenesis in breast cancer, as well
as the underlying mechanisms. Double immunohistochemical staining for CCL18 and
CD34/CD31/vWF was performed in 80 breast cancer samples to study the correlation
between CCL18+ TAMs and microvascular density (MVD). Cocultures of TAMs with
human umbilical vein endothelial cells (HUVECs) were used to model the
inflammatory microenvironment, and CCL18-induced angiogenesis was evaluated both
in vitro and in vivo. We demonstrated that CCL18+ TAM infiltration positively
associated with MVD in breast cancer samples, which was correlated with tumor
metastasis and poor prognosis. We confirmed, both in vitro and in vivo, that
CCL18 and VEGF synergistically promoted endothelial cell migration and
angiogenesis. Conversely, blocking CCL18 or VEGF with neutralizing antibodies
synergistically inhibited the promigratory effects of TAMs. Silencing PITPNM3, a
putative CCL18 receptor, on the surface of HUVECs abrogated CCL18-mediated
promigration and the enhancement of HUVEC tube formation, independently of VEGFR
signaling. Moreover, CCL18 exposure induced the endothelial-mesenchymal
transformation and activated ERK and Akt/GSK-3beta/Snail signaling in HUVECs,
thereby contributing to its pro-angiogenic effects. In conclusion, our findings
suggest that CCL18 released from TAMs promotes angiogenesis and tumor progression
in breast cancer; thus, CCL18 may serve as a novel target for anti-angiogenic
therapies.
PMID- 26416450
TI - Acquired resistance to 5-fluorouracil via HSP90/Src-mediated increase in
thymidylate synthase expression in colon cancer.
AB - 5-fluorouracil (5-FU), one of the first-line chemotherapeutic agents for the
treatment of gastrointestinal malignancies, has shown limited efficacy. The
expression of thymidylate synthase (TYMS) has been reported to be associated with
the resistance to 5-FU. Here, we demonstrate that the enhanced HSP90 function and
subsequent activation of Src induce expression of TYMS and acquired resistance to
5-FU in colon cancer. We show that the persistent 5-FU treatment granted 5-FU
sensitive HCT116 colon cancer cells morphologic, molecular, and behavioral
characteristic of the epithelial-mesenchymal transition (EMT), contributing to
emergence of acquired resistance to 5-FU. HCT116/R, a HCT116 colon cancer cell
subline carrying acquired resistance to 5-FU, showed increased expression and
activation of HSP90's client proteins and transcriptional up-regulation of TYMS.
Forced overexpression of HSP90 or constitutive active Src in HCT116 cells
increased TYMS expression. Conversely, pharmacological blockade of HSP90 or Src
in HCT116/R cells effectively suppressed the changes involved in 5-FU resistance
in vitro and xenograft tumor growth, hematogenous spread, and metastatic tumor
development in vivo. This study suggests a novel function of HSP90-Src pathway in
regulation of TYMS expression and acquisition of 5-FU resistance. Thus,
therapeutics targeting this pathway may be an effective clinical strategy to
overcome 5-FU resistance in colon cancer.
PMID- 26416451
TI - p62/IMP2 stimulates cell migration and reduces cell adhesion in breast cancer.
AB - p62/IMP2 is an oncofetal protein that is overexpressed in several types of
cancer, and is a member of the family of insulin-like growth factor 2 mRNA
binding proteins. We previously reported that high levels of p62/IMP2
autoantibody are present in sera from cancer patients, compared to healthy
individuals. Here, we report the overexpression of p62/IMP2 in tumor tissues of
72 out of 104 cases of human breast cancer, and high levels of p62/IMP2
autoantibody in patients' sera (in 63 out of 216 cases). To explore the role of
p62/IMP2 in breast cancer progression, we generated p62/IMP2 transfected variants
of two human breast cancer cell lines: MDA-MB-231 and LM2-4. Using in vitro
assays we found that overexpression of p62/IMP2 can increase cell migration, and
reduce cell adhesion to extracellular matrix (ECM) proteins. A Human
Extracellular Matrix and Adhesion Molecules qPCR array was performed with our
generated variants, and it identified a group of mRNAs whose expression was
altered with p62/IMP2 overexpression, including connective tissue growth factor
(CTGF) mRNA - which we show to be a p62/IMP2 binding partner. Overall, our
results provide new insights into the molecular mechanism by which p62/IMP2 can
contribute to breast cancer progression.
PMID- 26416452
TI - EMMPRIN regulates tumor growth and metastasis by recruiting bone marrow-derived
cells through paracrine signaling of SDF-1 and VEGF.
AB - EMMPRIN, a cell adhesion molecule highly expressed in a variety of tumors, is
associated with poor prognosis in cancer patients. Mechanistically, EMMPRIN has
been characterized to contribute to tumor development and progression by
controlling the expression of MMPs and VEGF. In the present study, by using
fluorescently labeled bone marrow-derived cells (BMDCs), we found that the down
regulation of EMMPRIN expression in cancer cells reduces tumor growth and
metastasis, and is associated with the reduced recruitment of BMDCs. Further
protein profiling studies suggest that EMMPRIN controls BMDC recruitment through
regulating the secretion of soluble factors, notably, VEGF and SDF-1. We
demonstrate that the expression and secretion of SDF-1 in tumor cells are
regulated by EMMPRIN. This study reveals a novel mechanism by which EMMPRIN
promotes tumor growth and metastasis by recruitment of BMDCs through controlling
secretion and paracrine signaling of SDF-1 and VEGF.
PMID- 26416453
TI - Association of glutathione S-transferase T1 and M1 polymorphisms with prostate
cancer susceptibility in populations of Asian descent: a meta-analysis.
AB - BACKGROUND: Genetic polymorphism was hypothesized to be reason of variation in
prostate cancer incidence among different racial group. Based on that published
data on the association of prostate cancer susceptibility with polymorphisms in
genes encoding Glutathione S-transferases (GSTs) were inconclusive, the aim of
this study was to more precisely address the role of GSTs polymorphisms
(especially, GSTT1 and GSTM1 deletions) on prostate cancer risk in Asian descent.
METHODS: A meta-analysis including 8 articles with 711 cases and 1122 controls
for GSTT1 and 1098 cases and 1588 controls for GSTM1 was performed. RESULTS:
Significantly increased prostate cancer risk was found among subjects carrying
GSTM1 null genotype (odds ratio (OR) = 1.403; 95% confidence interval (CI) =
1.088 - 1.808) but not among subjects carrying GSTT1 deletion genotype (OR =
0.959; 95%CI = 0.709 - 1.297). When stratified by country, the null genotype of
GSTT1 neither increased nor decreased prostate cancer risk significantly in China
(OR = 1.355; 95%CI = 0.895 - 2.049), Japan (OR = 0.812; 95%CI = 0.545 - 1.211),
and Korea (OR = 1.056; 95%CI = 0.727 - 1.534). While significant association of
elevated prostate cancer risk with GSTM1 deletion were found in China (OR =
1.665; 95%CI = 1.324 - .094) and Korea (OR = 1.914; 95%CI = 1.311 - 2.793) but
not in Japan (OR = 0.980; 95%CI = 0.726 - 1.321). CONCLUSIONS: In summary, this
meta-analysis suggested that the null genotype of GSTM1 rather than GSTT1 may be
involved in the etiology of prostate cancer in Asian population.
PMID- 26416454
TI - MiR-200b regulates autophagy associated with chemoresistance in human lung
adenocarcinoma.
AB - Chemoresistance remains a major clinical problem in combating human lung
adenocarcinoma (LAD), and abnormal autophagy is closely associated with this
phenomenon. In the present study, an inverse correlation between miR-200b and
autophagy-associated gene 12 (ATG12) expressions was observed in docetaxel
resistant (SPC-A1/DTX and H1299/DTX) and sensitive (SPC-A1 and H1299) LAD cells
as well as in tissue samples. Further study showed that miR-200b directly
targeted ATG12 in LAD. Moreover, miR-200b-dependent ATG12 downregulation
inhibited autophagy and enhanced the chemosensitivity of SPC-A1/DTX and H1299/DTX
cells both in vivo and in vitro. LAD chemoresistance is therefore closely related
to downregulation of miR-200b and the corresponding upregulation of ATG12. These
results provide new evidence for the mechanisms governing the microRNA (miRNA)
ATG12 network and their possible contribution to autophagy modulation and LAD
chemoresistance.
PMID- 26416455
TI - TQ inhibits hepatocellular carcinoma growth in vitro and in vivo via repression
of Notch signaling.
AB - Thymoquinone (TQ) has been reported to possess anti-tumor activity in various
types of cancer. However, its effects and molecular mechanism of action in
hepatocellular carcinoma (HCC) are still not completely understood. We observed
that TQ inhibited tumor cell growth in vitro, where treatment with TQ arrested
the cell cycle in G1 by upregulating p21 and downregulating cyclinD1 and CDK2
expression; moreover, TQ induced apoptosis by decreasing expression of Bcl-2 and
increasing expression of Bax. Simultaneously, TQ demonstrated a suppressive
impact on the Notch pathway, where overexpression of NICD1 reversed the
inhibitory effect of TQ on cell proliferation, thereby attenuating the repressive
effects of TQ on the Notch pathway, cyclinD1, CDK2 and Bcl-2, and also
diminishing upregulation of p21 and Bax. In a xenograft model, TQ inhibited HCC
growth in nude mice; this inhibitory effect in vivo, as well as of HCC cell
growth in vitro, was associated with a discernible decline in NICD1 and Bcl-2
levels and a dramatic rise in p21 expression. In conclusion, TQ inhibits HCC cell
growth by inducing cell cycle arrest and apoptosis, achieving these effects by
repression of the Notch signaling pathway, suggesting that TQ represents a
potential preventive or therapeutic agent in HCC patients.
PMID- 26416456
TI - Isolated locoregional recurrence patterns of breast cancer after mastectomy and
adjuvant systemic therapies in the contemporary era.
AB - PURPOSE: To evaluate the recurrence patterns in a series of patients who
presented with isolated locoregional recurrences (ILRRs) after mastectomy and
adjuvant systemic therapies in the contemporary era. METHODS: A total of 235
patients who developed ILRRs between 2005 and 2013 were classified into subgroups
based on nodal status, hormone receptor status, and biologic subtype. The annual
frequency of recurrences, association between biologic subtype and interval to
recurrence (ITR), and anatomical distribution were evaluated. RESULTS: For the
entire group, recurrence peaked within the first 3 years after mastectomy, and
then decreased significantly with time. Node-positive patients were observed to
recur early, and a greater proportion recurred within 5 years (86.7% vs. 72.8%,
chi2 = 6.83, P = 0.008) than did node-negative subgroup. Overall, the median ITR
was 33.2 (range, 4.5 - 236) months. Biologic subtype specific median ITR were
43.3 (7.9 - 236.0) months for luminal A, 42.2 (6.1 - 143.3) months for luminal B,
23.8 (6.9 - 47.3) months for luminal HER2, 18.2 (6.6 - 117.5) months for HER2,
and 21.8 (4.5 - 138.2) months for TNBC, and their difference was statistically
significant (chi2 = 7.4, P = 0.001). Among all ILRRs, 51.5% (n = 121) were
isolated to regional nodes. CONCLUSIONS: We demonstrates that the time course is
consistent with previous description, biologic subtype is associated with ITR,
and regional nodes is the most common place for recurrences in this series of
patients who developed ILRRs following mastectomy and contemporary adjuvant
systemic therapies but without PMRT.
PMID- 26416457
TI - Detection of recurrent cytogenetic aberrations in multiple myeloma: a comparison
between MLPA and iFISH.
AB - Multiple myeloma (MM) is a genetically heterogeneous disease with diverse
clinical characteristics and outcomes. Recently, multiplex ligation-dependent
probe amplification (MLPA) has emerged as an effective and robust method for the
detection of cytogenetic aberrations in MM patients. In the present study, MLPA
analysis was applied to analyze cytogenetics of CD138 tumor cells of 59 MM
samples, and its result was compared, retrospectively, with the interphase
fluorescence in situ hybridization (iFISH) data. We firstly established the
normal range of each of the 42 diagnostic probes using healthy donor samples. A
total of 151 aberrations were detected in 59 patient samples, and 49/59 cases
(83.1%) harbored at least one copy number variation. Overall, 0-7 aberrations
were detected per case using MLPA, indicating the heterogeneity and complexity of
MM cytogenetics. We showed the high efficiency of MLPA and the high congruency of
the two methods to assess cytogenetic aberrations. Considering that MLPA analysis
is not reliable when the aberration only exits in a small population of tumor
cells, it is essential to use both MLPA and iFISH as complementary techniques for
the diagnosis of MM.
PMID- 26416458
TI - KRAS mutations affect prognosis of non-small-cell lung cancer patients treated
with first-line platinum containing chemotherapy.
AB - KRAS mutations seem to indicate a poor outcome in Non-Small-Cell Lung Cancer
(NSCLC) but such evidence is still debated. The aim of this planned ancillary
study within the TAILOR trial was to assess the prognostic value of KRAS
mutations in advanced NSCLC patients treated with platinum-based first-line
chemotherapy. Patients (N = 540), enrolled in the study in 52 Italian hospitals,
were centrally genotyped twice in two independent laboratories for EGFR and KRAS
mutational status.Of these, 247 patients were eligible and included in the
present study. The primary endpoint was overall survival (OS) according to KRAS
mutational status in patients harboring EGFR wild-type.Sixty (24.3%) out of 247
patients harbored KRAS mutations. Median OS was 14.3 months and 10.6 months in
wild-type and mutated KRAS patients, respectively (unadjusted Hazard Ratio
[HR]=1.41, 95%Confidence Interval [CI]: 1.03-1.94 P = 0.032; adjusted HR=1.39,
95%CI: 1.00-1.94 P = 0.050). This study, with all consecutive patients genotyped,
indicates that the presence of KRAS mutations has a mild negative impact on OS in
advanced NSCLC patient treated with a first-line platinum-containing regimen.
TRIAL REGISTRATION: clinicaltrials.gov identifierNCT00637910.
PMID- 26416459
TI - Sorafenib-induced defective autophagy promotes cell death by necroptosis.
AB - Autophagy is one of the main cytoprotective mechanisms that cancer cells deploy
to withstand the cytotoxic stress and survive the lethal damage induced by anti
cancer drugs. However, under specific conditions, autophagy may, directly or
indirectly, induce cell death. In our study, treatment of the Atg5-deficient
DU145 prostate cancer cells, with the multi-tyrosine kinase inhibitor, sorafenib,
induces mitochondrial damage, autophagy and cell death. Molecular inhibition of
autophagy by silencing ULK1 and Beclin1 rescues DU145 cells from cell death
indicating that, in this setting, autophagy promotes cell death. Re-expression of
Atg5 restores the lipidation of LC3 and rescues DU145 and MEF atg5-/- cells from
sorafenib-induced cell death. Despite the lack of Atg5 expression and LC3
lipidation, DU145 cells form autophagosomes as demonstrated by transmission and
immuno-electron microscopy, and the formation of LC3 positive foci. However, the
lack of cellular content in the autophagosomes, the accumulation of long-lived
proteins, the presence of GFP-RFP-LC3 positive foci and the accumulated p62
protein levels indicate that these autophagosomes may not be fully functional.
DU145 cells treated with sorafenib undergo a caspase-independent cell death that
is inhibited by the RIPK1 inhibitor, necrostatin-1. Furthermore, treatment with
sorafenib induces the interaction of RIPK1 with p62, as demonstrated by
immunoprecipitation and a proximity ligation assay. Silencing of p62 decreases
the RIPK1 protein levels and renders necrostatin-1 ineffective in blocking
sorafenib-induced cell death. In summary, the formation of Atg5-deficient
autophagosomes in response to sorafenib promotes the interaction of p62 with RIPK
leading to cell death by necroptosis.
PMID- 26416460
TI - Vanadium toxicity in the thymic development.
AB - The purpose of this study was to define the toxic effects of vanadium on thymic
development in broilers fed on diets supplemented with 0, 5, 15, 30, 45 and 60
mg/kg of vanadium for 42 days. We examined the changes of relative weigh, cell
cycle phase, apoptotic cells, and protein expression of Bcl-2, Bax, and caspase-3
in the thymus by the methods of flow cytometry, TUNEL (terminal-deoxynucleotidyl
transferase mediated nick end labeling) and immunohistochemistry. The results
showed that dietary high vanadium (30 mg/kg, 45 mg/kg and 60 mg/kg) caused the
toxic effects on thymic development, which was characterized by decreasing
relative weigh, increasing G0/G1 phase (a prolonged nondividing state), reducing
S phase (DNA replication) and proliferating index (PI), and increasing
percentages of apoptotic thymocytes. Concurrently, the protein expression levels
of Bax and caspase-3 were increased, and protein expression levels of Bcl-2 were
decreased. The thymic development suppression caused by dietary high vanadium
further leads to inhibitive effects on T lymphocyte maturity and activity, and
cellular immune function. The above-mentioned results provide new evidences for
further understanding the vanadium immunotoxicity. In contrast, dietary 5 mg/kg
vanadium promoted the thymic development by increasing relative weigh, decreasing
G0/G1 phase, increasing S phase and PI, and reducing percentages of apoptotic
thymocytes when compared to the control group and high vanadium groups.
PMID- 26416462
TI - Prognosis of long-term survival considering disease-specific death in patients
with chronic myeloid leukemia.
AB - In patients with chronic myeloid leukemia (CML), first-line imatinib treatment
leads to 8-year overall survival (OS) probabilities above 80%. Many patients die
of reasons unrelated to CML. This work tackled the reassessment of prognosis
under particular consideration of the probabilities of dying of CML. Analyses
were based on 2290 patients with chronic phase CML treated with imatinib in six
clinical trials. 'Death due to CML' was defined by death after disease
progression. At 8 years, OS was 89%. Of 208 deceased patients, 44% died of CML.
Higher age, more peripheral blasts, bigger spleen and low platelet counts were
significantly associated with increased probabilities of dying of CML and
determined a new long-term survival score with three prognostic groups. Compared
with the low-risk group, the patients of the intermediate- and the high-risk
group had significantly higher probabilities of dying of CML. The score was
successfully validated in an independent sample of 1120 patients. In both
samples, the new score differentiated probabilities of dying of CML better than
the Sokal, Euro and the European Treatment and Outcome Study (EUTOS) score. The
new score identified 61% low-risk patients with excellent long-term outcome and
12% high-risk patients. The new score supports the prospective assessment of long
term antileukemic efficacy and risk-adapted treatment.
PMID- 26416461
TI - CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse
after reduced intensity HCT.
AB - We have recently described a specialized subset of human natural killer (NK)
cells with a CD56(dim)CD57(+)NKG2C(+) phenotype that expand specifically in
response to cytomegalovirus (CMV) reactivation in hematopoietic cell transplant
(HCT) recipients and exhibit properties characteristic of adaptive immunity. We
hypothesize that these cells mediate relapse protection and improve post-HCT
outcomes. In 674 allogeneic HCT recipients, we found that those who reactivated
CMV had lower leukemia relapse (26% (17-35%), P=0.05) and superior disease-free
survival (DFS) (55% (45-65%) P=0.04) 1 year after reduced intensity conditioning
(RIC) compared with CMV seronegative recipients who experienced higher relapse
rates (35% (27-43%)) and lower DFS (46% (38-54%)). This protective effect was
independent of age and graft-vs-host disease and was not observed in recipients
who received myeloablative regimens. Analysis of the reconstituting NK cells
demonstrated that CMV reactivation is associated with both higher frequencies and
greater absolute numbers of CD56(dim)CD57(+)NKG2C(+) NK cells, particularly after
RIC HCT. Furthermore, expansion of these cells at 6 months posttransplant
independently trended toward a lower 2-year relapse risk. Together, our data
suggest that the protective effect of CMV reactivation on posttransplant relapse
is in part driven by adaptive NK cell responses.
PMID- 26416463
TI - Validation of the Questionnaire to Identify Knee Symptoms (QuIKS) using Rasch
analysis.
AB - BACKGROUND: The Questionnaire to Identify Knee Symptoms (QuIKS) was recently
developed to promote activity by screening for experiences related to early
symptoms in people with emergent chronic knee pain problems, such as
osteoarthritis (OA) - like knee pain. The main purpose of the current study was
to evaluate measurement properties of the QuIKS using Rasch analysis in a sample
of people with knee symptoms consistent with symptomatic knee OA. METHOD: This
study used cross-sectional data. The sample was 200 subjects along the following
knee health continuum: pain-free healthy knees (n = 55) from a university
community, knee pain with no knee OA diagnosis (n = 111) from a university
affiliated medical clinic, and patients with surgeon-diagnosed symptomatic knee
OA awaiting high tibial osteotomy (n = 34) from a sports medicine surgical
clinic. The 13-item QuIKS was evaluated for its factor structure, item- and
person-fit, item's category response structure, differential item functioning by
sex and obesity status, local item dependency, unidimensionality, and test
precision. Subsequently, the QuIKS underwent known-groups analysis and convergent
validity with the Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS:
In the QuIKS, each item's category response structure was modified. No
differential item functioning was observed. Local item dependency informed the
formation of four testlets. This refined QuIKS obtained summary fit to the Rasch
measurement model, unidimensionality, reliability (person separation index =
0.82), and interval-level scoring. Subsequently, the Rasch-validated QuIKS (QuIKS
R) demonstrated excellent known-groups validity and good convergent validity with
the KOOS (Spearman's rho = 0.45 to 0.77). CONCLUSIONS: The QuIKS-R provides
interval-level quantification of knee symptoms-related experiences in people with
knee symptoms consistent with symptomatic knee OA. Its scores might be useful for
clinicians for promoting activity in individuals with early symptoms consistent
with symptomatic knee OA.
PMID- 26416464
TI - Awareness, experiences and perceptions of telehealth in a rural Queensland
community.
AB - BACKGROUND: Telehealth can offer alternative options for receiving healthcare
services in rural locations, improving access and reducing costs associated with
traveling for services. However, the full potential of telehealth has not been
realised with slow and fragmented uptake. This study describes the awareness,
experiences and perceptions of telehealth in an Australian rural community.
METHODS: Semi-structured interviews were undertaken with 47 participants from
three rural towns in the Darling Downs region of Queensland. Content analysis was
used to abstract themes and core concepts from the interviews. RESULTS: Three
participants were healthcare providers who had all previously used telehealth in
their clinical practice. Twenty-seven (57 %) participants regularly travelled to
access specialist healthcare. While 28 (60 %) participants were aware of
telehealth, only six (13 %) had actually used telehealth services; three as
patients and three as healthcare providers. Major themes evident included:
acceptance of the need to travel; paternalism and empowerment; and trust and
misconceptions. CONCLUSIONS: For telehealth initiatives to be successful, there
needs to be greater public awareness and understanding of the potential benefits
of telehealth. Empowering patients as partners in the delivery of healthcare may
be an important factor in the growth of telehealth services.
PMID- 26416465
TI - F-box protein interactions with the hallmark pathways in cancer.
AB - F-box proteins (FBP) are the substrate specifying subunit of Skp1-Cul1-FBP (SCF)
type E3 ubiquitin ligases and are responsible for directing the ubiquitination of
numerous proteins essential for cellular function. Due to their ability to
regulate the expression and activity of oncogenes and tumour suppressor genes,
FBPs themselves play important roles in cancer development and progression. In
this review, we provide a comprehensive overview of FBPs and their targets in
relation to their interaction with the hallmarks of cancer cell biology,
including the regulation of proliferation, epigenetics, migration and invasion,
metabolism, angiogenesis, cell death and DNA damage responses. Each cancer
hallmark is revealed to have multiple FBPs which converge on common signalling
hubs or response pathways. We also highlight the complex regulatory interplay
between SCF-type ligases and other ubiquitin ligases. We suggest six highly
interconnected FBPs affecting multiple cancer hallmarks, which may prove sensible
candidates for therapeutic intervention.
PMID- 26416466
TI - Tumor-extracellular matrix interactions: Identification of tools associated with
breast cancer progression.
AB - Several evidences support the concept that cancer development and progression are
not entirely cancer cell-autonomous processes, but may be influenced, and
possibly driven, by cross-talk between cancer cells and the surrounding
microenvironment in which, besides immune cells, stromal cells and extracellular
matrix (ECM) play a major role in regulating distinct biologic processes. Stroma
and ECM-related signatures proved to influence breast cancer progression, and to
contribute to the identification of tumor phenotypes resistant to cytotoxic and
hormonal treatments. The possible clinical implications of the interplay between
tumor cells and the microenvironment, with special reference to ECM remodelling,
will be discussed in this review.
PMID- 26416467
TI - Moving Knowledge Acquisition From the Lecture Hall to the Student Home: A
Prospective Intervention Study.
AB - BACKGROUND: Podcasts are popular with medical students, but the impact of podcast
use on learning outcomes in undergraduate medical education has not been studied
in detail. OBJECTIVE: Our aim was to assess the impact of podcasts accompanied by
quiz questions and lecture attendance on short- and medium-term knowledge
retention. METHODS: Students enrolled for a cardio-respiratory teaching module
were asked to prepare for 10 specific lectures by watching podcasts and
submitting answers to related quiz questions before attending live lectures.
Performance on the same questions was assessed in a surprise test and a retention
test. RESULTS: Watching podcasts and submitting answers to quiz questions (versus
no podcast/quiz use) was associated with significantly better test performance in
all items in the surprise test and 7 items in the retention test. Lecture
attendance (versus no attendance) was associated with higher test performance in
3 items and 1 item, respectively. In a linear regression analysis adjusted for
age, gender, and overall performance levels, both podcast/quiz use and lecture
attendance were significant predictors of student performance. However, the
variance explained by podcast/quiz use was greater than the variance explained by
lecture attendance in the surprise test (38.7% vs. 2.2%) and retention test
(19.1% vs. 4.0%). CONCLUSIONS: When used in conjunction with quiz questions,
podcasts have the potential to foster knowledge acquisition and retention over
and above the effect of live lectures.
PMID- 26416468
TI - Optimum initial loading dose of vancomycin for pneumonia caused by methicillin
resistant Staphylococcus aureus.
PMID- 26416469
TI - Human papillomavirus and polyomavirus coinfections among Chinese men who have sex
with men.
PMID- 26416470
TI - Clinical evaluation of the newly developed infectious disease/fever screening
radar system using the neural network and fuzzy grouping method for travellers
with suspected infectious diseases at Narita International Airport Clinic.
PMID- 26416471
TI - Telaprevir-based therapy for treatment of HIV-1 and hepatitis C virus co-infected
patients: An early access programme.
AB - OBJECTIVES: HPC3005 is a multicentre, open-label, telaprevir trial in HCV/HIV
coinfected patients with severe fibrosis or compensated cirrhosis. METHODS:
Patients were treated with telaprevir 750 mg every 8 h (1125 mg if on efavirenz)
plus pegylated interferon-alpha (PEG-IFN, 180 MUg once-weekly) and ribavirin
(RBV, 800 mg/day) for 12 weeks, followed by 36 weeks of PEG-IFN/RBV. RESULTS:
Mean age was 44 years, 97/118 patients were male and all were Caucasian, 68 had
severe fibrosis and 50 had cirrhosis. Seventy-eight had HCV RNA levels >=800 000
IU/mL, 72 had HCV genotype 1a, baseline HIV RNA was <50 copies/mL in 112
patients. Overall, 114/118 patients continued antiretroviral treatment, 4 were
untreated. Seventy-five patients received tenofovir and 74 emtricitabine; in
addition 53 received atazanavir/ritonavir, 43 raltegravir, and 24 efavirenz. By
intention-to-treat, 78 (66%) patients achieved SVR24. Nineteen discontinued
telaprevir, 8 for virological endpoint, 5 for adverse events (2 anaemia, 2 rash,
1 asthenia), 5 for non-compliance and 1 withdrew consent. The most common adverse
events were anaemia (36 patients), thrombocytopaenia (33), rash (26), bilirubin
increase (17), and neutropenia (16). CONCLUSIONS: In this early access programme
in coinfected patients with severe fibrosis or cirrhosis, 66% of patients
achieved SVR. The most common adverse events were haematological. CLINICAL TRIAL
NUMBER: NCT01500616.
PMID- 26416472
TI - Prognostic potential of 1,3-beta-d-glucan levels in bronchoalveolar lavage fluid
samples.
AB - OBJECTIVES: The objective of this study was to investigate the prognostic
potential of 1,3-beta-d-glucan (BDG) testing in bronchoalveolar lavage fluid
(BALF) samples. METHODS: A total of 300 BALF samples from 252 patients were
investigated for BDG (Fungitell((r)) assay). Prognostic potential of BALF BDG was
evaluated by using: i.) Kaplan-Meier analysis, and ii.) multivariable Cox hazard
regression analyses. RESULTS: BALF BDG levels were found to be significantly
higher in samples with Candida spp. colonization (p < 0.001). A total of 61/252
patients (24.2%) died within 90-days of BALF sampling (18.1% of patients with
BALF BDG <200 pg/mL, 32.4% with BALF BDG >=200 pg/mL). Kaplan-Meier analysis
revealed that overall cumulative 90-day mortality was significantly higher in
those with BALF BDG levels >=200 pg/mL when compared to those with levels <200
pg/mL (log-rank p = 0.006, Breslow p = 0.005 and Tarone-Ware p = 0.005). The
multivariable Cox regression analysis showed that BALF BDG levels were a strong
predictor of 90-day overall mortality, with a hazard ratio of 1.048 (per 100
pg/mL increase of BALF BDG). CONCLUSION: False positive BALF BDG results in the
presence of Candida spp. colonization of the lower respiratory tract may explain
the limited diagnostic potential of BALF BDG testing. In contrast, prognostic
potential of BALF BDG may be promising.
PMID- 26416473
TI - Clindamycin and rifampicin: No bull's eye without a target.
PMID- 26416474
TI - Salmonella in the tropical household environment--Everyday, everywhere.
AB - OBJECTIVES: To determine the prevalence of Salmonella in the environment of case
and control houses, and compare serovars isolated from cases and their houses.
METHODS: From 2005 to 2008, we tested samples from houses of 0-4 year old cases
and community controls in Darwin and Palmerston for Salmonella. Case isolates
were compared with environmental isolates. S. Ball and S. Urbana isolates were
compared using Multiple Amplification of Phage Locus Typing (MAPLT) and Multiple
Locus Variable number of tandem repeat Analysis (MLVA). RESULTS: Salmonella were
found in 47/65 (72%) case houses and 18/29 (62%) control houses; these
proportions were not significantly different. In 21/47 (45%) houses, case and
environmental isolates (from animal faeces, soil and vacuums) were
indistinguishable. Multiple serovars were isolated from 20 (31%) case and 6 (21%)
control houses. All but one environmental isolate are known human pathogens in
the Northern Territory (NT). Each of the four pairs of S. Ball and S. Urbana were
indistinguishable. CONCLUSIONS: Animal faeces were the most likely source of
salmonellosis in cases. The similar prevalence of house isolates suggests that
Salmonella is ubiquitous in this environment. The distinction of S. Ball and S.
Urbana subtypes enabled linkage of human illness to environmental exposure.
Environmental contamination with Salmonella is an important source of sporadic
infection in children in the tropics.
PMID- 26416475
TI - Individual and household-level risk factors for sporadic salmonellosis in
children.
AB - OBJECTIVES: To explore risk factors for sporadic salmonellosis at the individual
and household level in children in tropical Darwin, where animal faeces
contaminated with Salmonella is thought to be common. METHODS: A 2-year community
based case-control study of children aged 0-4 years residing in Darwin and
Palmerston from June 2006. Variables included behaviour, health, food, family and
housing characteristics. Environmental samples were taken from houses of case and
control children. RESULTS: Of children whose parents were contacted, 59/131 cases
and 95/222 controls were included. Salmonella was isolated from 41/56 (73%) case
houses and 18/29 (62%) control houses (p = 0.29). Multivariate analyses showed
breastfeeding 0.16 (p = 0.02), increasing age (months) 0.89 (p = 0.00) and daily
vacuuming 0.18 (p = 0.06) were protective; consuming powdered formula milk 4.88
(p = 0.02), pet ownership 4.86 (p = 0.02), oral contact with animals 7.85 (p =
0.05), recent antibiotic use 10.01 (p = 0.03) and sweeping in the presence of
children 3.73 (p = 0.04) were associated with sporadic salmonellosis.
CONCLUSIONS: Salmonellosis in children under 5 years of age is associated with
potentially modifiable risk factors other than food. Breastfeeding beyond 6
months, careful hygiene when preparing formula milk and around pets, frequent
cleaning of infant play areas especially quick removal of animal faeces are
behaviours likely to reduce childhood sporadic salmonellosis.
PMID- 26416476
TI - Characterization of structural elements in native autoinducing peptides and non
native analogues that permit the differential modulation of AgrC-type quorum
sensing receptors in Staphylococcus aureus.
AB - Staphylococcus aureus uses short macrocyclic peptides (i.e., autoinducing
peptides, or AIPs) to assess its local population density in a cell-cell
signaling mechanism called quorum sensing (QS). At high cell numbers, this
pathogen can initiate many virulent behaviors that allow for the establishment of
infection. Binding of the AIP signal to its cognate transmembrane AgrC-type
receptor is a critical event in the QS signaling cascade; consequently,
interference of AIP:receptor interactions may have the potential to prevent and
eradicate certain S. aureus infections. To date, four pairs of AIP:AgrC receptors
have been identified in S. aureus, each pair being utilized by a specific S.
aureus group (I-IV). Other staphylococcal species also use closely related, but
distinct, AIP:AgrC pairs to control QS. We seek to develop non-native ligands
capable of intercepting AIP:AgrC binding in each S. aureus group and in related
species. As these bacteria may use their respective AIP signal to attenuate the
QS systems of other groups/species, such ligands would provide valuable chemical
tools to probe possible interference mechanisms in a range of contexts. In the
current study, we used solution-phase NMR techniques to characterize the 3-D
structures of a set of known native and non-native peptides that have
differential modulatory activity in certain AgrC receptors. Analysis of these
structures revealed several distinct structural motifs that belay differential
activity in selected S. aureus AgrC receptors (i.e., AgrC-I, AgrC-II, and AgrC
III). The results of this study can be leveraged for the design of new synthetic
ligands with enhanced selectivities and potencies for these AgrC receptors.
PMID- 26416477
TI - Orexin Receptor Antagonists: Historical Perspectives and Future Opportunities.
AB - The orexin receptors OX1 and OX2 play important roles in the regulation of sleep
wake cycles, feeding, reward and energy homeostasis. Since these G protein
coupled receptors were deorphanised in 1998, more than 200 patents containing
orexin receptor antagonists have been filed and, in 2014, suvorexant
(Belsomra(r)) became the first of these compounds to receive approval from the
FDA. Suvorexant is a dual orexin receptor antagonist (DORA) which is available
for the treatment of insomnia. This review provides a historical perspective on
the discovery and development of DORAs as well as selective OX1 receptor
antagonists (1-SORAs) and selective OX2 receptor antagonists (2-SORAs). 2-SORAs
are under clinical evaluation for their ability to modulate sleep, and 1-SORAs
have shown promise for the treatment of addiction in pre-clinical animal models.
Detailed medicinal chemistry case studies are presented and future opportunities
for orexin receptor antagonists are considered.
PMID- 26416478
TI - Effects of cyano, ethynyl and ethylenedioxy groups on the photophysical
properties of carbazole-based porphyrins.
AB - The synthesis and photophysical properties of cyano and ethynyl substituted
carbazole-based porphyrins were investigated. The introduction of ethynyl groups
induced red shifts, while that of cyano groups induced blue shifts of their
absorption bands, which was supported by MO calculations. Ethylenedioxy-appended
porphyrins were also prepared via a coupling reaction. The conjugated and
electronic substituent effects on the photophysical properties of the carbazole
based porphyrins have been elucidated by using both experimental results and
calculations. Among these porphyrins, the ethylenedioxy-appended selenaporphyrin
displayed intensified and red-shifted absorption in the NIR region up to 1178 nm.
PMID- 26416479
TI - Mobile Phone App Aimed at Improving Iron Intake and Bioavailability in
Premenopausal Women: A Qualitative Evaluation.
AB - BACKGROUND: Low iron intake can lead to iron deficiency, which can result in
impaired health and iron-deficiency anemia. A mobile phone app, combining
successful dietary strategies to increase bioavailable iron with strategies for
behavior change, such as goal setting, monitoring, feedback, and resources for
knowledge acquisition, was developed with the aim to increase bioavailable iron
intake in premenopausal women. OBJECTIVE: To evaluate the content, usability, and
acceptability of a mobile phone app designed to improve intake of bioavailable
dietary iron. METHODS: Women aged 18-50 years with an Android mobile phone were
invited to participate. Over a 2-week period women were asked to interact with
the app. Following this period, semistructured focus groups with participants
were conducted. Focus groups were audio recorded and analyzed via an inductive
open-coding method using the qualitative analysis software NVivo 10. Themes were
identified and frequency of code occurrence was calculated. RESULTS: Four focus
groups (n=26) were conducted (age range 19-36 years, mean 24.7, SD 5.2). Two
themes about the app's functionality were identified (frequency of occurrence in
brackets): interface and design (134) and usability (86). Four themes about the
app's components were identified: goal tracker (121), facts (78), photo diary
(40), and games (46). A number of suggestions to improve the interface and design
of the app were provided and will inform the ongoing development of the app.
CONCLUSIONS: This research indicates that participants are interested in iron and
their health and are willing to use an app utilizing behavior change strategies
to increase intake of bioavailable iron. The inclusion of information about the
link between diet and health, monitoring and tracking of the achievement of
dietary goals, and weekly reviews of goals were also seen as valuable components
of the app and should be considered in mobile health apps aimed at adult women.
PMID- 26416481
TI - Behavioural abnormalities in children with new-onset nephrotic syndrome receiving
corticosteroid therapy: results of a prospective longitudinal study.
AB - BACKGROUND: Corticosteroid therapy can cause behavioural abnormalities in
children with nephrotic syndrome. The objective of this study was to explore the
timing of the appearance of abnormalities in their first episode. METHODS: Forty
five children with a first episode of idiopathic nephrotic syndrome (30 aged 2-5
and 15 aged 6-14 years) were assessed for behavioural problems using the Child
Behaviour Checklist (CBCL) before, and after 6 and 12 weeks of oral steroid
treatment. Sixty healthy children were included as controls. RESULTS: In both age
groups, marked abnormalities of externalising behaviour were noticed,
specifically in the domains of aggressive behaviour and attention problems.
Clinical range or borderline externalising abnormalities were present in 73% of
the younger children and 60% of the schoolchildren after 6 weeks of treatment. In
the schoolchildren, abnormal internalising behaviour was also noted at 6 weeks,
in 40% at borderline level and in 20% within the clinical range. Elevated scores
were observed for the anxious/depressed and withdrawn/depressed domains. Most
changes persisted at the 12-week observation. CONCLUSIONS: Children of both age
groups showed significant attention problems and aggressive and abnormal
externalising behaviour within 6 weeks of starting treatment. Parents should be
informed and counselled about this potential adverse effect of steroid therapy.
PMID- 26416480
TI - Can office blood pressure readings predict masked hypertension?
AB - BACKGROUND: Studies in children with chronic kidney disease indicate a high
prevalence of masked hypertension detected by ambulatory blood pressure
monitoring (ABPM). However, it is not well known if the frequency of masked
hypertension is related to the level of normal casual blood pressure (BP).
METHODS/RESULTS: We hypothesized that lower levels of normal casual BP are
associated with a lower prevalence of masked hypertension. Data from the chronic
kidney disease (CKiD) cohort were analyzed cross-sectionally across multiple
visits. The majority of children with normal casual BP also had normal wake and
sleep ABP (60 %), even at the highest percentiles of casual BP. The frequency of
masked hypertension was lower in children with casual BP <=25th percentile versus
those with casual BP in 26-50th percentile and casual BP in 51-90th percentile
during both wake and sleep periods. In children with the lowest normal casual BP
levels (<=25th percentile), the frequency of abnormal mean wake or sleep ABP was
2-7 %, and of abnormal BP load was 6-16 %. CONCLUSIONS: These data suggest that
masked hypertension is unlikely if the casual BP is found to be in the low normal
range.
PMID- 26416482
TI - The Abundant Histone Chaperones Spt6 and FACT Collaborate to Assemble, Inspect,
and Maintain Chromatin Structure in Saccharomyces cerevisiae.
AB - Saccharomyces cerevisiae Spt6 protein is a conserved chromatin factor with
several distinct functional domains, including a natively unstructured 30-residue
N-terminal region that binds competitively with Spn1 or nucleosomes. To uncover
physiological roles of these interactions, we isolated histone mutations that
suppress defects caused by weakening Spt6:Spn1 binding with the spt6-F249K
mutation. The strongest suppressor was H2A-N39K, which perturbs the point of
contact between the two H2A-H2B dimers in an assembled nucleosome. Substantial
suppression also was observed when the H2A-H2B interface with H3-H4 was altered,
and many members of this class of mutations also suppressed a defect in another
essential histone chaperone, FACT. Spt6 is best known as an H3-H4 chaperone, but
we found that it binds with similar affinity to H2A-H2B or H3-H4. Like FACT, Spt6
is therefore capable of binding each of the individual components of a
nucleosome, but unlike FACT, Spt6 did not produce endonuclease-sensitive
reorganized nucleosomes and did not displace H2A-H2B dimers from nucleosomes.
Spt6 and FACT therefore have distinct activities, but defects can be suppressed
by overlapping histone mutations. We also found that Spt6 and FACT together are
nearly as abundant as nucleosomes, with ~24,000 Spt6 molecules, ~42,000 FACT
molecules, and ~75,000 nucleosomes per cell. Histone mutations that destabilize
interfaces within nucleosomes therefore reveal multiple spatial regions that have
both common and distinct roles in the functions of these two essential and
abundant histone chaperones. We discuss these observations in terms of different
potential roles for chaperones in both promoting the assembly of nucleosomes and
monitoring their quality.
PMID- 26416484
TI - Oxidative Etching of Hexagonal Boron Nitride Toward Nanosheets with Defined Edges
and Holes.
AB - Lateral surface etching of two-dimensional (2D) nanosheets results in holey 2D
nanosheets that have abundant edge atoms. Recent reports on holey graphene showed
that holey 2D nanosheets can outperform their intact counterparts in many
potential applications such as energy storage, catalysis, sensing, transistors,
and molecular transport/separation. From both fundamental and application
perspectives, it is desirable to obtain holey 2D nanosheets with defined hole
morphology and hole edge structures. This remains a great challenge for graphene
and is little explored for other 2D nanomaterials. Here, a facile, controllable,
and scalable method is reported to carve geometrically defined pit/hole shapes
and edges on hexagonal boron nitride (h-BN) basal plane surfaces via oxidative
etching in air using silver nanoparticles as catalysts. The etched h-BN was
further purified and exfoliated into nanosheets that inherited the hole/edge
structural motifs and, under certain conditions, possess altered optical bandgap
properties likely induced by the enriched zigzag edge atoms. This method opens up
an exciting approach to further explore the physical and chemical properties of
hole- and edge-enriched boron nitride and other 2D nanosheets, paving the way
toward applications that can take advantage of their unique structures and
performance characteristics.
PMID- 26416483
TI - MicroRNAs and Their Targets Are Differentially Regulated in Adult and Neonatal
Mouse CD8+ T Cells.
AB - Immunological memory, which protects organisms from re-infection, is a hallmark
of the mammalian adaptive immune system and the underlying principle of
vaccination. In early life, however, mice and other mammals are deficient at
generating memory CD8+ T cells, which protect organisms from intracellular
pathogens. The molecular basis that differentiates adult and neonatal CD8+ T
cells is unknown. MicroRNAs (miRNAs) are both developmentally regulated and
required for normal adult CD8+ T cell functions. We used next-generation
sequencing to identify mouse miRNAs that are differentially regulated in adult
and neonatal CD8+ T cells, which may contribute to the impaired development of
neonatal memory cells. The miRNA profiles of adult and neonatal cells were
surprisingly similar during infection; however, we observed large differences
prior to infection. In particular, miR-29 and miR-130 have significant
differential expression between adult and neonatal cells before infection.
Importantly, using RNA-Seq, we detected reciprocal changes in expression of
messenger RNA targets for both miR-29 and miR-130. Moreover, targets that we
validated include Eomes and Tbx21, key genes that regulate the formation of
memory CD8+ T cells. Notably, age-dependent changes in miR-29 and miR-130 are
conserved in human CD8+ T cells, further suggesting that these developmental
differences are biologically relevant. Together, these results demonstrate that
miR-29 and miR-130 are likely important regulators of memory CD8+ T cell
formation and suggest that neonatal cells are committed to a short-lived effector
cell fate prior to infection.
PMID- 26416486
TI - The mechanism of a phosphazene-phosphazane rearrangement.
AB - The phosphazene-phosphazane rearrangement of N3P3Cl5O(CH2)2OC(=O)CMe=CH2 (8) has
been examined in detail using one and two dimensional NMR ((31)P, (1)H)
spectroscopy and mass spectrometry. The mixed phosphazene-phosphazane
[NPCl2]2[N((CH2)2OC(=O)CMe=CH2)P(O)Cl] (14), [NPCl2]2[NHP(O)Cl] (13) and a two
ring assembly [NPCl2]2[NP(O{(NPCl2)2(N((CH2)2OC(=O)CMe=CH2)P(O)}] (15) have all
been detected in the product mixture. The rate of the rearrangement has been
measured at five temperatures by (31)P and (1)H NMR. The reaction is first order
in 8 (T1/2 at 111 degrees is 4.65 hours). The activation enthalpy is positive
and the activation entropy is negative. A mechanism involving competing intra and
inter molecular processes which fits the product distribution and kinetic data
has been proposed. Several other methyacrylphosphazenes were examined under the
same thermolysis conditions. The rearrangement was observed and the rates
obtained in cases where the (CH2)2 spacer unit of the methacrylate was replaced
by linear and branched propyl units. The rearrangement was not observed when the
methacrylate was appended to a spirocyclic unit, the spacer unit was extended to
the n-butyl group and when the methacrylate unit was replaced by a methoxy group.
These results are all consistent with the proposed mechanism. This investigation
resolves conflicting results previous reported for the rearrangement.
PMID- 26416485
TI - Effect of selective CCK1 receptor antagonism on accommodation and tolerance of
intestinal gas in functional gut disorders.
AB - BACKGROUND: Participants with functional gut disorders develop gas retention and
symptoms in response to intestinal gas loads that are well tolerated by healthy
subjects. To determine the role of cholecystokinin (CCK1 ) receptors on gas
transit and tolerance in women with functional gut disorders. METHODS: In 12
healthy women, and 24 women with functional gut disorders (12 dyspepsia and 12
constipation-predominant irritable bowel syndrome) gas was infused into the
jejunum at 12 mL/min for 3 h with simultaneous duodenal lipid infusion
(intralipid 1 kcal/min), while measuring anal gas evacuation and abdominal
symptoms on a 0-6 score scale. Triple-blind paired studies during iv infusion of
dexloxiglumide (2.5 mg/kg bolus plus 5 mg/kg h continuous infusion), a selective
CCK1 inhibitor, or saline (control) were performed in random order. RESULTS:
During saline infusion participants with functional gut disorders developed
significantly greater gas retention and abdominal symptoms than healthy subjects
(394 +/- 40 mL vs 265 +/- 35 mL and 2.8 +/- 0.3 vs 1.9 +/- 0.4 highest abdominal
symptom score, respectively; P < 0.05 for both). Dexloxiglumide increased gas
retention in both groups (514 +/- 35 mL and 439 +/- 60 mL, respectively; P =
0.033 vs saline for both); however, despite the larger retention, dexloxiglumide
reduced abdominal symptoms (2.3 +/- 0.2 score and 0.8 +/- 0.3 score,
respectively; P = 0.05 vs saline for both). Post-hoc analysis showed that, the
decrease in abdominal symptoms was more pronounced in those participants with
functional gut disorders with higher basal abdominal symptoms than in the rest (P
= 0.037). CONCLUSION: Inhibition of CCK1 receptors by dexloxiglumide increases
intestinal gas retention and reduces abdominal symptoms in response to by
intestinal gas loads. European Clinical Trials Database (EudraCT 2005-003338-16).
PMID- 26416487
TI - Round and round we go.
PMID- 26416488
TI - Studies towards the stabilisation of a mushroom phytase produced by submerged
cultivation.
AB - A novel phytase from Ganoderma australe G24 was produced by submerged cultivation
and recovery. Liquid and solid forms of phytase were developed; both types of
product were formulated using different additives. Ganoderma australe G24 phytase
was very stable in liquid form with NaCl and sodium acetate buffer. Solid form
products were obtained by spray-drying using different polymers to encapsulate
the phytase and the capsules obtained were analyzed by electron microscopy.
Micrographs confirmed micro and nanoparticles formed with maltodextrin (300 nm to
7-8 um) without the presence of agglomerates. The use of maltodextrin for solid
formulation of G. australe G24 phytase is recommended, and resulted in good
stability after the drying process and during storage (shelf life). Kinetic
models of phytase inactivation in the microencapsulated powders over time were
proposed for the different stabilizing additives. Inactivation rate constants,
half-lives and D values (decimal reduction time) were obtained. Phytase
encapsulated with maltodextrin remained stable after 90 days, with k 0.0019 day(
1) and a half-life (t1/2) of 367.91 days(-1).
PMID- 26416490
TI - Modifiable factors and cognitive dysfunction in breast cancer survivors: a mixed
method systematic review.
AB - PURPOSE: It is unknown why some breast cancer survivors experience cancer-related
cognitive impairments (CRCI) after cancer treatment, and modifiable risk factors
for CRCI remain to be explicated. This mixed-method systematic review synthesizes
quantitative and qualitative evidence for relationships between modifiable
factors and CRCI in breast cancer survivors who receive chemotherapy as part of
their treatment. METHODS: Keyword Searches of PubMed/Medline, PsychINFO, and
CINAHL were performed for January 2005 through June 2015. Studies that provided
data on associations between modifiable biological, behavioral, environmental,
and psychosocial factors and cognition were included. RESULTS: Twenty-two
quantitative studies and five qualitative studies were identified after applying
inclusion and exclusion criteria yielding evidence for significant relationships
among modifiable biological (inflammatory cytokines), behavioral (sleep quality,
physical activity), and psychosocial (stress, distress, affect) factors and CRCI.
CONCLUSION: Many women unfortunately experience CRCI after breast cancer
chemotherapy, with limited treatment options available to improve cognitive
function. This review synthesizes current evidence to support the associations
between modifiable factors and CRCI and can inform research to evaluate these
factors prospectively. The clinical implications of these findings suggest that
lifestyle factors such as physical activity, stress management, and sleep quality
may be appropriate targets for behavioral interventions to improve cognitive
function following breast cancer chemotherapy; however, further research is
necessary.
PMID- 26416492
TI - Decreased connexin 43 in astrocytes inhibits the neuroinflammatory reaction in an
acute mouse model of neonatal sepsis.
AB - Neonatal sepsis is common in neonatal intensive care units, often complicated by
injury to the immature brain. Previous studies have shown that the expression of
the gap junction protein connexin 43 (Cx43) in the brain decreases when
stimulated by neuro-inflammatory drugs such as lipopolysaccharide (LPS). Here we
showed that partial deletion of Cx43 in astrocytes resulted in weakened
inflammatory responses. The up-regulation of pro-inflammatory cytokines was
significantly reduced in mice with partial deletion of Cx43 in astrocytes
compared with wild-type littermates after systemic LPS injection. Moreover,
microglial activation was inhibited in mice with partial deletion of Cx43. These
results showed that Cx43 in astrocytes plays a critical role in neuro
inflammatory responses. This work provides a potential therapeutic target for
inhibiting neuro-inflammatory responses in neonatal sepsis.
PMID- 26416493
TI - Medication use and potentially inappropriate medications in those with limited
prognosis living in residential aged care.
AB - AIM: To compare the prevalence in residential aged care (RAC) of preventative and
potentially inappropriate medications (PIMs) in those who died within 12 months
versus those alive after 12 months. METHODS: Firstly, a cross-sectional survey of
6196 people living in RAC in Auckland. Secondly, a research physician searched
electronic hospital records in one District Health Board for a sub-sample (n =
222) of these residents. Classes of medications and dates of death were obtained
from the Ministry of Health databases. Those who died versus those alive at 12
months were compared. RESULTS: Over half of the 6196 participants received
antihypertensives and/or antiplatelet agents. Cardiovascular preventative
medications were significantly more common in those who died within 12 months.
Seventy percent in high-level care received psychotropics. PIMs were commonly
used. CONCLUSIONS: Use of preventative medications is common in RAC, especially
during the last year of life. Psychotropics are very commonly used, despite being
potentially inappropriate.
PMID- 26416491
TI - Dysgeusia and weight loss under treatment with vismodegib: benefit of nutritional
management.
AB - PURPOSE: Whereas vismodegib is effective in the treatment of locally
advanced/metastatic basal cell carcinoma, dysgeusia and weight loss are common
side effects of such treatment. The main objective of this study was to monitor
the nutritional status of vismodegib-treated patients. Secondary objective was to
assess the incidence of dysgeusia and the benefit of early nutritional
management. METHODS: This prospective study included all patients who started
vismodegib between October 2011 and May 2013 at Nantes University Hospital. Prior
to July 2012, patients treated with vismodegib had not received any specific
nutritional management (Historical cohort). Body weight and presence of dysgeusia
were recorded monthly. Patients treated after July 2012 (Nutrition cohort) were
evaluated by a physician of the Nutrition Support Unit and received dietary
counseling at vismodegib initiation. A standardized nutritional management
protocol was initiated in case of significant weight loss. RESULTS: Forty-five
patients (21 and 24 in the Nutrition and Historical cohort, respectively) were
enrolled. In the Nutrition cohort, five patients (24 %) were undernourished at
vismodegib initiation, and the 6-month cumulative incidence of dysgeusia was 71
%. Eight patients (38 %) and 13 patients (54 %) had a weight loss greater than 5
% in the Nutrition and Historical cohort, respectively (p = 0.3727). CONCLUSION:
The results of this pilot study suggest the benefit of early nutritional
screening. The potential benefit of nutritional support in this setting warrants
further investigation.
PMID- 26416494
TI - Irrigation of Cutaneous Abscesses Does Not Improve Treatment Success.
AB - STUDY OBJECTIVE: Irrigation of the cutaneous abscess cavity is often described as
a standard part of incision and drainage despite no randomized, controlled
studies showing benefit. Our goal is to determine whether irrigation of a
cutaneous abscess during incision and drainage in the emergency department (ED)
decreases the need for further intervention within 30 days compared with no
irrigation. METHODS: We performed a single-center, prospective, randomized,
nonblinded study of ED patients receiving an incision and drainage for cutaneous
abscess, randomized to irrigation or no irrigation. Patient characteristics and
postprocedure pain visual analog scale score were obtained. Thirty-day telephone
follow-up was conducted with a standardized data form examining need for further
intervention, which was defined as repeated incision and drainage, antibiotic
change, or abscess-related hospital admission. RESULTS: Of 209 enrolled patients,
187 completed follow-up. The irrigation and no-irrigation groups were similar
with respect to diabetes, immunocompromise, fever, abscess size, cellulitis, and
abscess location, but the irrigation group was younger (mean age 36 versus 40
years) and more often treated with packing (89% versus 75%) and outpatient
antibiotics (91% versus 73%). The need for further intervention was not different
in the irrigation (15%) and no-irrigation (13%) groups (difference 2%; 95%
confidence interval -8% to 12%). There was no difference in pain visual analog
scale scores (5.6 versus 5.7; difference 0.1; 95% confidence interval -0.7 to
0.9). CONCLUSION: Although there were baseline differences between groups,
irrigation of the abscess cavity during incision and drainage did not decrease
the need for further intervention.
PMID- 26416495
TI - Biasing the odds: Approaches to capturing, understanding and exploiting
functional selectivity in GPCRs.
AB - There is significant expectation in the pharmacological community that an
understanding of biased signalling will lead to the development of new drugs and
a better understanding of molecular targets in the in vivo context. I think it is
safe to say that Pharma is withholding judgment on the promise and potential of
what they view as an interesting pharmacological curiosity. That said, beyond
successes of biased ligands in clinical trials and their appearance on the
market, what it is need is a clear plan and the right tools and analytical
methods to characterize functional selectivity from in cellulo to in vivo. In
this issue of Methods, we have put together a series of articles that help lay
out a methodological and analytical framework to help get us there.
PMID- 26416496
TI - Mislocalization-related disease gene discovery using gene expression based
computational protein localization prediction.
AB - Protein sorting is an important mechanism for transporting proteins to their
target subcellular locations after their synthesis. Mutations on genes may
disrupt the well regulated protein sorting process, leading to a variety of
mislocation related diseases. This paper proposes a methodology to discover such
disease genes based on gene expression data and computational protein
localization prediction. A kernel logistic regression based algorithm is used to
successfully identify several candidate cancer genes which may cause cancers due
to their mislocation within the cell. Our results also showed that compared to
the gene co-expression network defined on Pearson correlation coefficients, the
nonlinear Maximum Correlation Coefficients (MIC) based co-expression network give
better results for subcellular localization prediction.
PMID- 26416498
TI - Acute kidney injury: New antagonist prevents I/R injury.
PMID- 26416497
TI - Phosphate and FGF-23 homeostasis after kidney transplantation.
AB - Dysregulated phosphate metabolism is a common consequence of chronic kidney
disease, and is characterized by a high circulating level of fibroblast growth
factor (FGF)-23, hyperparathyroidism, and hyperphosphataemia. Kidney
transplantation can elicit specific alterations to phosphate metabolism that
evolve over time, ranging from severe hypophosphataemia (<0.5 mmol/l) to
hyperphosphataemia (>1.50 mmol/l) and high FGF-23 levels. The majority of renal
transplant recipients develop hypophosphataemia during the first 3 months after
transplantation as a consequence of relatively slow adaptation of FGF-23 and
parathyroid hormone levels to restored renal function, and the influence of
immunosuppressive drugs. By 3-12 months after transplantation, phosphate
homeostasis is at least partially restored in the majority of recipients, which
is paralleled by a substantially reduced risk of cardiovascular-associated
morbidity and mortality compared with the pre-transplantation setting. Many renal
transplant recipients, however, exhibit persistent abnormalities in phosphate
homeostasis, which is often due to multifactorial causes, and may contribute to
adverse outcomes on the cardiovascular system, kidney, and bone. Dietary and
pharmacologic interventions might improve phosphate homeostasis in renal
transplant recipients, but additional insight into the pathophysiology of
transplantation-associated abnormalities in phosphate homeostasis is needed to
further optimize disease management and improve prognosis for renal transplant
recipients.
PMID- 26416500
TI - Risk factors: Contribution of low GFR to the global burden of disease.
PMID- 26416499
TI - Nephrology research--the past, present and future.
AB - Important advances have been made in basic and clinical nephrology research over
the past decade, with improved pathological insights into various disease
processes and the introduction of new treatments for diseases such as atypical
haemolytic uraemic syndrome. However, many challenges remain. In this Viewpoint,
we asked five Nature Reviews Nephrology Advisory Board members, who have been
associated with the journal since its launch in November 2005, to reflect on the
progress and roadblocks of the past 10 years. They also comment on areas where
effort and money should be invested and how they expect the field to progress in
the next 10 years.
PMID- 26416501
TI - Energy regulation in context: Free-living female arctic ground squirrels modulate
the relationship between thyroid hormones and activity among life history stages.
AB - Thyroid hormones (THs), key regulators of lipid and carbohydrate metabolism, are
likely modulators of energy allocation within and among animal life history
stages. Despite their role in modulating metabolism, few studies have
investigated whether THs vary among life history stages in free-living animals or
if they exhibit stage-specific relationships to total energy expenditure and
activity levels. We measured plasma total triiodothyronine (tT3) and thyroxine
(tT4) at four, discrete life history stages of female arctic ground squirrels
from two different populations in northern Alaska to test whether plasma THs
correlate with life history stage-specific changes in metabolic rate and energy
demand. We also tested whether THs explained individual variation in aboveground
activity levels within life history stages. T3 peaked during lactation and was
lowest during pre-hibernation fattening, consistent with known changes in basal
metabolism and core body temperature. In contrast, T4 was elevated shortly after
terminating hibernation but remained low and stable across other life-history
stages in the active season. THs were consistently higher in the population that
spent more time above-ground but the relationship between THs and activity varied
among life history stages. T3 was positively correlated with activity only during
lactation (r(2)=0.50) whereas T4 was positively correlated with activity
immediately following lactation (r(2)=0.48) and during fattening (r(2)=0.53). Our
results support the hypothesis that THs are an important modulator of basal
metabolism but also suggest that the relationship between THs and activity varies
among life history stages.
PMID- 26416502
TI - The association between job strain and coronary heart disease: a meta-analysis of
prospective cohort studies.
AB - BACKGROUND: Studies about work stress and the risk of coronary heart disease
(CHD) have yielded inconsistent results. This meta-analysis aimed to investigate
the association between job strain and the risk of CHD. METHODS: We searched
PubMed and Embase databases for studies reporting data on job strain and the risk
of CHD. Studies were included if they reported multiple-adjusted relative risk
(RR) with 95% confidence interval (CI) with respect to CHD from job strain.
RESULTS: Fourteen prospective cohort studies comprising 232,767 participants were
included. The risk of CHD was increased in high-strain (RR 1.26; 95% CI 1.12
1.41) and passive jobs (RR 1.14; 95% CI 1.02-1.29) but not in active jobs (RR
1.09; 95% CI 0.97-1.22), when compared with low-strain group. The increased risk
of CHD in high-strain and passive jobs was mainly driven by studies with a follow
up duration of >= 10 years. Neither the low-control (RR 1.06; 95% CI 0.93-1.19)
nor high-demand (RR 1.13; 95% CI 0.97-1.32) dimension was independently
associated with the risk of CHD. CONCLUSIONS: Individuals with high-strain and
passive jobs were more likely to experience a CHD event. Intervention programs
incorporating individual and organizational levels are crucial for reducing job
strain and the risk of CHD.
PMID- 26416503
TI - Advances in Peptides as Therapeutic Drugs.
PMID- 26416504
TI - Executive function and weight status in children: A one-year longitudinal
perspective.
AB - There is considerable evidence for an association between obesity and impaired
executive function (EF) in adolescents and adults. However, little research has
examined EF in overweight or obese children. Furthermore, data on EF in
underweight individuals is lacking. In addition, there is no consensus on the
directionality of the relationship between Body Mass Index (BMI) and EF, and
longitudinal studies are rare. Thus, the present study examined whether children
differ in their performance on a battery of EF tasks depending on their weight
status (underweight, normal-weight, overweight), and investigated the
longitudinal cross-lagged associations between EF and BMI. Hot EF (delay of
gratification, affective decision-making), cool EF (attention shifting,
inhibition, working memory [WM] updating), and BMI were assessed in 1,657 German
elementary-school children at two time points, approximately one year apart.
Overweight children exhibited slightly poorer attention shifting, WM updating,
and affective decision-making abilities as compared to normal-weight children.
Unexpectedly, they did not show any deficits in inhibition or delay of
gratification. EF levels of underweight children did not differ significantly
from those of normal-weight children. Furthermore, poor attention shifting and
enhanced affective decision-making predicted a slightly higher BMI one year
later, and a higher BMI also predicted poorer attention shifting and WM updating
one year later. The latter association between BMI and subsequent EF scores,
however, diminished when controlling for socioeconomic status. Results indicate
that hot and cool EF plays a role in the weight development of children, and
might be a promising factor to address in preventive interventions.
PMID- 26416505
TI - Application of Mannich bases to the synthesis of hydroxymethylated isoflavonoids
as potential antineoplastic agents.
AB - The regiospecific Mannich aminomethylation of 7-hydroxyisoflavonoids using
bis(N,N-dimethylamino)methane afforded C-8 substituted N,N-dimethylaminomethyl
adducts, and the regioselective aminomethylation of 5-hydroxy-7
methoxyisoflavonoids afforded predominantly the C-6 substituted N,N
dimethylaminomethyl adducts. Acetylation of these C-6 or C-8 Mannich bases with
potassium acetate in acetic anhydride provided access to the corresponding
acetoxymethyl derivatives that were subsequently converted to hydroxymethyl- and
methoxymethyl-substituted 5-hydroxy- or 7-hydroxyisoflavonoids related to
naturally occurring flavonoids. The C-8 acetoxymethyl, hydroxymethyl or
methoxymethyl-substituted isoflavonoids possessed promising inhibitory potency in
the low micromolar range in a prostate cancer PC-3 cell proliferation assay.
PMID- 26416506
TI - The importance of defining focal assemblages when evaluating amphibian and
reptile responses to land use.
AB - Habitat loss and degradation are primary threats to amphibians and reptiles, but
the relative effects of common land uses on assemblages and the mechanisms that
underlie faunal responses are poorly studied. We reviewed the effects of four
prevalent types of habitat alteration (urbanization, agriculture, livestock
grazing, and silviculture) on amphibian and reptile species richness and
abundance by summarizing reported responses in the literature and by estimating
effect sizes across studies for species richness in each land-use type. We then
used a multinomial model to classify species as natural habitat specialists,
generalists, and disturbed habitat specialists and examined variation in effect
sizes for each land-use type according to habitat specialization categories.
There were mixed conclusions from individual studies, some reporting negative,
neutral, or positive effects of land use on species richness and total abundance.
A large proportion of studies reported species-specific effects of individual
species abundance. However, in our analysis of effect sizes, we found a general
trend of negative effects of land use on species richness. We also demonstrate
that habitat associations of common species and species turnover can explain
variation in the effect of land use on herpetofauna. Our review highlights the
pervasive negative effects of common land uses on amphibians and reptiles, the
importance of identifying groups vulnerable to land-use change (e.g., forest
associated species) in conservation studies, and the potential influence of
disturbance-associated species on whole assemblage analyses.
PMID- 26416507
TI - Mitochondrial regulation of macrophage cholesterol homeostasis.
AB - This review explores the relationship between mitochondrial structure and
function in the regulation of macrophage cholesterol metabolism and proposes that
mitochondrial dysfunction contributes to loss of the elegant homeostatic
mechanisms which normally maintain cellular sterol levels within defined limits.
Mitochondrial sterol 27-hydroxylase (CYP27A1) can generate oxysterol activators
of liver X receptors which heterodimerise with retinoid X receptors, enhancing
the transcription of ATP binding cassette transporters (ABCA1, ABCG1, and ABCG4),
that can remove excess cholesterol via efflux to apolipoproteins A-1, E, and high
density lipoprotein, and inhibit inflammation. The activity of CYP27A1 is
regulated by the rate of supply of cholesterol substrate to the inner
mitochondrial membrane, mediated by a complex of proteins. The precise identity
of this dynamic complex remains controversial, even in steroidogenic tissues, but
may include steroidogenic acute regulatory protein and the 18 kDa translocator
protein, together with voltage-dependent anion channels, ATPase AAA domain
containing protein 3A, and optic atrophy type 1 proteins. Certainly,
overexpression of StAR and TSPO proteins can enhance macrophage cholesterol
efflux to apoA-I and/or HDL, while perturbations in mitochondrial function, or
changes in the expression of mitochondrial fusion proteins, alter the efficiency
of cholesterol efflux. Molecules which can sustain or improve mitochondrial
function or increase the activity of the protein complex involved in cholesterol
transfer may have utility in resolving the problem of dysregulated macrophage
cholesterol homeostasis, a condition which may contribute to inflammation,
atherosclerosis, nonalcoholic steatohepatitis, osteoblastic bone resorption, and
some disorders of the central nervous system.
PMID- 26416508
TI - Sexually dimorphic morphology and swimming performance relationships in wild-type
zebrafish Danio rerio.
AB - This study compared prolonged swimming performance (Ucrit ) between male and
female Danio rerio, and characterized how body shape was associated with this
performance measure in each sex. When swimming in small (n = 6) mixed-sex groups
at 28 degrees C, males swam, on average, over 10 cm s(-1) faster than females
despite being significantly smaller. Body shape was sexually dimorphic, with
males and females exhibiting small, but statistically significant differences in
most aspects of body shape. Body shape explained 18 and 43% of the variation in
Ucrit among males and females. In general, effects of body shape on swimming
performance appeared to be sex limited, whereby different aspects of body shape
affected performance in each sex, although the contribution of the distance
between pelvic and anal fins to swimming performance was weakly sexually
antagonistic.
PMID- 26416510
TI - Correction. NILVAD protocol: a European multicenter double-blind placebo
controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease.
PMID- 26416509
TI - Divergence and adaptive evolution of the gibberellin oxidase genes in plants.
AB - BACKGROUND: The important phytohormone gibberellins (GAs) play key roles in
various developmental processes. GA oxidases (GAoxs) are critical enzymes in GA
synthesis pathway, but their classification, evolutionary history and the forces
driving the evolution of plant GAox genes remain poorly understood. RESULTS: This
study provides the first large-scale evolutionary analysis of GAox genes in
plants by using an extensive whole-genome dataset of 41 species, representing
green algae, bryophytes, pteridophyte, and seed plants. We defined eight
subfamilies under the GAox family, namely C19-GA2ox, C20-GA2ox, GA20ox,GA3ox,
GAox-A, GAox-B, GAox-C and GAox-D. Of these, subfamilies GAox-A, GAox-B, GAox-C
and GAox-D are described for the first time. On the basis of phylogenetic
analyses and characteristic motifs of GAox genes, we demonstrated a rapid
expansion and functional divergence of the GAox genes during the diversification
of land plants. We also detected the subfamily-specific motifs and potential
sites of some GAox genes, which might have evolved under positive selection.
CONCLUSIONS: GAox genes originated very early-before the divergence of bryophytes
and the vascular plants and the diversification of GAox genes is associated with
the functional divergence and could be driven by positive selection. Our study
not only provides information on the classification of GAox genes, but also
facilitates the further functional characterization and analysis of GA oxidases.
PMID- 26416512
TI - Correction. Heavier smoking may lead to a relative increase in waist
circumference: evidence for a causal relationship from a Mendelian randomisation
meta-analysis.
PMID- 26416511
TI - Associations of pregnancy-associated plasma protein-A level with essential
hypertension and hypertensive disorders in pregnancy in Chinese population: a
meta-analysis of 20 research studies involving 3332 individuals.
AB - OBJECTIVE: To explore the associations between serum pregnancy-associated plasma
protein-A (PAPP-A) level, and essential hypertension (EH) and hypertensive
disorders in pregnancy (HDP) in Chinese population. METHODS: Pertinent studies
were independently searched in PubMed, Embase, Cochrane Library, Chinese
Biomedical Database (CBM), Wanfang databases and China National Knowledge
Infrastructure (CNKI). The standardised mean difference (SMD) with 95% CIs was
used to estimate the size of the effect. The subgroup analyses and meta
regression analysis were performed to identify the sources of heterogeneity among
studies. Sensitivity analysis was conducted to assess the stability of the
results. The publication bias between studies was examined by using Begg's funnel
plots and Egger's test. RESULTS: A total of 20 studies involving 1493 patients
and 1839 controls were included in the current meta-analysis. The PAPP-A level
was significantly higher in EH patients than in controls (SMD=1.960, 95% CI 1.305
to 2.615, p<0.001), and significant associations were observed in all subgroups.
The PAPP-A level was also significantly higher in HDP patients than in healthy
pregnant women (SMD=2.249; 95% CI 1.324 to 3.173, p<0.001). The positive
association between PAPP-A level and the risk of HDP was consistently observed in
all subgroups except the subgroup with low NOS score. CONCLUSIONS: The present
meta-analysis suggests that an elevated PAPP-A level may be associated with
susceptibilities to EH and HDP.
PMID- 26416513
TI - Distinct subgroups of paroxysmal nocturnal hemoglobinuria (PNH) with cytopenia:
results from South Korean National PNH Registry.
AB - We retrospectively assessed the clinical characteristics of patients with
paroxysmal nocturnal hemoglobinuria (PNH) according to severity of cytopenia. A
total of 282 patients with hematological parameters assessed at the time of
diagnosis of PNH were included. There were 24 patients with PNH/severe aplastic
anemia (SAA) (at least two of the three criteria; hemoglobin <=8 g/dL; absolute
neutrophil count (ANC) <0.5 * 10(9)/L; platelet count <20 * 10(9)/L), 96 patients
with PNH/aplastic anemia (AA) (at least two of the three criteria; hemoglobin
<=10 g/dL; ANC 0.5-1.5 * 10(9)/L; platelet count 20-100 * 10(9)/L), and 162
classic PNH patients. Compared with the classic PNH subgroup, the PNH/SAA
subgroup had a significantly lower median granulocyte PNH clone size (26.7 vs.
51.0 %, P = 0.021) and lower incidence of lactate dehydrogenase >=1.5 times the
upper limit of normal (52.9 vs. 80.0 %, P = 0.049). The incidence of
thromboembolism was similar in both subgroups. Overall survival was significantly
lower in the PNH/SAA subgroup than in the classic PNH subgroup (P = 0.033). Our
findings suggest that identification of patients with PNH/SAA at the time of
diagnosis is important because of different clinical manifestations and poorer
outcome compared with patients with classic PNH (clinicaltrials.gov identifier:
#NCT01224483).
PMID- 26416514
TI - Cyclo(phenylalanine-proline) induces DNA damage in mammalian cells via reactive
oxygen species.
AB - Cyclo(phenylalanine-proline) is produced by various organisms such as animals,
plants, bacteria and fungi. It has diverse biological functions including anti
fungal activity, anti-bacterial activity and molecular signalling. However, a few
studies have demonstrated the effect of cyclo(phenylalanine-proline) on the
mammalian cellular processes, such as cell growth and apoptosis. In this study,
we investigated whether cyclo(phenylalanine-proline) affects cellular responses
associated with DNA damage in mammalian cells. We found that treatment of 1 mM
cyclo(phenylalanine-proline) induces phosphorylation of H2AX (S139) through ATM
CHK2 activation as well as DNA double strand breaks. Gene expression analysis
revealed that a subset of genes related to regulation of reactive oxygen species
(ROS) scavenging and production is suppressed by the cyclo(phenylalanine-proline)
treatment. We also found that cyclo(phenylalanine-proline) treatment induces
perturbation of the mitochondrial membrane, resulting in increased ROS,
especially superoxide, production. Collectively, our study suggests that
cyclo(phenylalanine-proline) treatment induces DNA damage via elevation of ROS in
mammalian cells. Our findings may help explain the mechanism underlying the
bacterial infection-induced activation of DNA damage response in host mammalian
cells.
PMID- 26416515
TI - Expression of pluripotency markers in the bovine uterus with adenomyosis.
AB - BACKGROUND: Adenomyosis is a proliferative uterine dysfunction with unknown
aetiology. One possible mechanism of its development involves disturbances in
stem cell differentiation in uterine tissue. Previously, we identified
pluripotent/multipotent cells in the bovine uterus, therefore our present study
focused on determining expression of pluripotency markers, NANOG, OCT4 and SOX2,
in bovine adenomyotic tissues and cells. FINDINGS: Immunolocalisation revealed
protein expression of NANOG, OCT4 and SOX2 in both normal and adenomyotic uteri.
mRNA expression for NANOG and OCT4 was increased in tissues obtained from uteri
with adenomyosis compared to controls, but at the protein level there were no
significant differences. mRNA expression for all three pluripotency markers was
higher in myometrial cells isolated from uteri with adenomyotic lesions than in
those isolated from normal uteri. The protein level of NANOG and SOX2 was
decreased in stromal cells from adenomyotic tissues, whereas the level of OCT4
and SOX2 was increased in myometrial cells obtained from dysfunctional uteri.
CONCLUSIONS: The results indicate significant changes in expression of
pluripotency markers in adenomyotic compared to normal uteri, which suggest the
involvement of uterine stem cells in adenomyosis.
PMID- 26416516
TI - Terrein reduces age-related inflammation induced by oxidative stress through
Nrf2/ERK1/2/HO-1 signalling in aged HDF cells.
AB - This study investigated whether multiple bioactivity of terrein such as anti
inflammatory and anti-oxidant inhibits age-related inflammation by promoting an
antioxidant response in aged human diploid fibroblast (HDF) cells. HDF cells were
cultured serially for in vitro replicative senescence. To create the ageing cell
phenotype, intermediate stage (PD31) HDF cells were brought to stress-induced
premature senescence (SIPS) using hydrogen peroxide (H2 O2). Terrein increased
cell viability even with H2O2 stress and reduced inflammatory molecules such as
intracellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), interleukin
1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha). Terrein reduced
also phospho-extracellular kinase receptor1/2 (p-EKR1/2) signalling in aged HDF
cells. SIPS cells were attenuated for age-related biological markers including
reactive oxygen species (ROS), senescence associated beta-galactosidase (SA beta
gal.) and the aforementioned inflammatory molecules. Terrein induced the
induction of anti-oxidant molecules, copper/zinc-superoxide defence (Cu/ZnSOD),
manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1) in SIPS cells.
Terrein also alleviated reactive oxygen species formation through the Nrf2/HO-1/p
ERK1/2 pathway in aged cells. The results indicate that terrein has an
alleviative function of age-related inflammation characterized as an anti
oxidant. Terrein might be a useful nutraceutical compound for anti-ageing.
PMID- 26416517
TI - Application of a patient-derived xenograft model in cytolytic viral activation
therapy for nasopharyngeal carcinoma.
AB - Nasopharyngeal carcinoma (NPC) is an Epstein Barr virus (EBV)-related malignancy
in which the tumor microenvironment plays a pivotal role in tumor progression.
Here, we developed two patient-derived xenograft (PDX) mouse lines from engrafted
NPC metastatic tumors. Positive staining for EBV-encoded small RNAs confirmed
that these tumors harbored EBV, and gene expression profile analyses further
showed that the PDX was highly similar to the primary parent tumor. In vivo drug
screening using the PDX system demonstrated that gemcitabine had the best
antitumor effect among the tested drugs. The donor of this PDX also showed
excellent responsiveness to gemcitabine treatment. The combination of gemcitabine
and valproic acid exerted synergistic antitumor effects. Further addition of
ganciclovir to this two-drug combination regimen enhanced cytolytic viral
activation, yielding the best antitumor response among tested regimens. Treatment
with this three-drug combination regimen decreased plasma EBV-DNA load, tumor
viral concentration, and the number of viable tumor cells to a greater extent
than the two-drug gemcitabine and valproic acid combination. These results
highlight the value of PDX models in the development of EBV-targeted strategies
to treat NPC.
PMID- 26416519
TI - Can Parsimonious Practice Please Patients and Practitioners? The Case of Spine
Imaging.
PMID- 26416518
TI - Reference values for amino acids and acylcarnitines in peripheral blood in
Quarter horses and American Miniature horses.
AB - BACKGROUND: Free amino acids and acylcarnitines circulating in the blood can be
used for diagnosis for metabolic illness and imbalances. To date, the normal
reference ranges of amino acids and acylcarnitines in horse peripheral blood have
not been established. In this study, the concentrations of 12 amino acids and 26
acylcarnitines were determined by tandem mass spectrometry in complete blood from
100 healthy horses (50 Quarter horses (QH) [23 males and 27 females] and 50
American Miniature horses (AMH) [15 males and 35 females]) with no signs of
metabolic disease. The means and standard deviations were determined and data
statistically analyzed. FINDINGS: Concentrations of short, medium, and long chain
acylcarnitines were significantly higher in male AMH than in male QH. The
concentrations of the amino acids alanine, arginine, glycine, proline
(glycogenic), and leucine (ketogenic) were higher in the QH than in the AMH.
Female AMH had higher concentrations of propionylcarnitine, leucine, proline,
arginine, and ornithine than female QH. CONCLUSIONS: Normal reference ranges of
amino acids and acylcarnitines were established for AMH and QH. Significant
differences were found in concentration of these compounds between breeds and
gender.
PMID- 26416520
TI - Cone-beam CT to assess bony fusion following anterior cervical interbody fusion.
AB - PURPOSE: Assessment of bony fusion following anterior cervical interbody fusion
(ACIF) is usually done by plain film or CT. We present the first clinical
application of Cone-Beam CT (CBCT) to evaluate bony fusion after ACIF. METHODS: A
56-year-old man with disc herniation at C6-C7 underwent ACIF surgery using a
compressed nanocrystalline hydroxyapatite interbody device (nanOss-C, Pioneer
Surgical Marquette, MI, USA) and a nanocrystalline hydroxyapatite bone graft
filler (nanOss Bioactive, Pioneer Surgical Marquette, MI, USA). Imaging follow-up
was performed by CBCT (NewTom 5G, QR Srl, Verona, Italy) at 1 day, 6 weeks, 3 and
9 months post-operatively. Two independent assessors quantitatively measured the
greyscale changes of the bone graft filler and qualitatively evaluated the bony
fusion process. RESULTS: Quantitative analysis of the images showed a steadily
increasing matrix density of the bone graft filler over the 9 months follow-up,
suggesting increasing calcification. Qualitative evaluation demonstrated
different stages of the bone fusion process within the disc space around the
cage, at the interface between cage and endplates, and at the interface between
bone graft filler and the endplates. CONCLUSIONS: CBCT provides high-resolution
cross-sectional imaging of the cervical spine after ACIF. For the first time, in
vivo evaluation of the bone graft filler within the centre of the
circumferentially radiodense cage and detailed cross-sectional evaluation of bone
fusion was achieved. Confirmation of these promising outlooks of CBCT in a large
cohort of ACIF patients is needed with regard to routine clinical application and
evaluation of different interbody devices.
PMID- 26416521
TI - Which is the best IVF/ICSI protocol to be used in poor responders receiving
growth hormone as an adjuvant treatment? A prospective randomized trial.
AB - This open label randomized study aims to define the best protocol to be used with
growth hormone in poor responders, with comparison performed to delineate which
protocol offers the best cycle outcomes. Two-hundred eighty-seven poor responders
were included. The patients were randomly allocated into four groups receiving
growth hormone (GH) as an adjuvant therapy added to either long or short agonist
protocol, miniflare or antagonist protocols. The short/GH gave significantly
lower mean number of oocytes when compared with the long/GH, antagonist/GH and
miniflare/GH (4 +/- 1.69 versus 5.06 +/- 1.83, 4.95 + / = 1.90 and4.98 +/- 2.51,
respectively p = 0.005). Considering the number of fertilized oocytes, the
long/GH showed significantly higher levels than short/GH and antagonist/GH (3.73
+/- 1.47 versus 3.02 +/- 1.52 and 2.89 +/- 1.14, respectively). The main drawback
is that it required significantly higher HMG dose and longer duration of
stimulation. The long/GH was superior when compared with the three protocols
regarding the number of oocytes retrieved and fertilized. But, when considering
the clinical pregnancy rates, there was a difference in favor of the long/GH but
not reaching a statistically significant value (ClinicalTrials.gov Identifier:
NCT01897324).
PMID- 26416522
TI - Using Video Games to Enhance Motivation States in Online Education: Protocol for
a Team-Based Digital Game.
AB - BACKGROUND: Video and computer games for education have been of interest to
researchers for several decades. Over the last half decade, researchers in the
health sector have also begun exploring the value of this medium. However, there
are still many gaps in the literature regarding the effective use of video and
computer games in medical education, particularly in relation to how learners
interact with the platform, and how the games can be used to enhance
collaboration. OBJECTIVE: The objective of the study is to evaluate a team-based
digital game as an educational tool for engaging learners and supporting
knowledge consolidation in postgraduate medical education. METHODS: A mixed
methodology will be used in order to establish efficacy and level of motivation
provided by a team-based digital game. Second-year medical students will be
recruited as participants to complete 3 matches of the game at spaced intervals,
in 2 evenly distributed teams. Prior to playing the game, participants will
complete an Internet survey to establish baseline data. After playing the game,
participants will voluntarily complete a semistructured interview to establish
motivation and player engagement. Additionally, metrics collected from the game
platform will be analyzed to determine efficacy. RESULTS: The research is in the
preliminary stages, but thus far a total of 54 participants have been recruited
into the study. Additionally, a content development group has been convened to
develop appropriate content for the platform. CONCLUSIONS: Video and computer
games have been demonstrated to have value for educational purposes.
Significantly less research has addressed how the medium can be effectively
utilized in the health sector. Preliminary data from this study would suggest
there is an interest in games for learning in the medical student body. As such,
it is beneficial to undertake further research into how these games teach and
engage learners in order to evaluate their role in tertiary and postgraduate
medical education in the future.
PMID- 26416524
TI - [BK 5103 "UV light-induced skin cancer" as a new occupational disease: Third
ordinance for amendment of the Occupational Diseases Act].
PMID- 26416523
TI - Improved orthologous databases to ease protozoan targets inference.
AB - BACKGROUND: Homology inference helps on identifying similarities, as well as
differences among organisms, which provides a better insight on how closely
related one might be to another. In addition, comparative genomics pipelines are
widely adopted tools designed using different bioinformatics applications and
algorithms. In this article, we propose a methodology to build improved
orthologous databases with the potential to aid on protozoan target
identification, one of the many tasks which benefit from comparative genomics
tools. METHODS: Our analyses are based on OrthoSearch, a comparative genomics
pipeline originally designed to infer orthologs through protein-profile
comparison, supported by an HMM, reciprocal best hits based approach. Our
methodology allows OrthoSearch to confront two orthologous databases and to
generate an improved new one. Such can be later used to infer potential protozoan
targets through a similarity analysis against the human genome. RESULTS: The
protein sequences of Cryptosporidium hominis, Entamoeba histolytica and
Leishmania infantum genomes were comparatively analyzed against three orthologous
databases: (i) EggNOG KOG, (ii) ProtozoaDB and (iii) Kegg Orthology (KO). That
allowed us to create two new orthologous databases, "KO + EggNOG KOG" and "KO +
EggNOG KOG + ProtozoaDB", with 16,938 and 27,701 orthologous groups,
respectively. Such new orthologous databases were used for a regular OrthoSearch
run. By confronting "KO + EggNOG KOG" and "KO + EggNOG KOG + ProtozoaDB"
databases and protozoan species we were able to detect the following total of
orthologous groups and coverage (relation between the inferred orthologous groups
and the species total number of proteins): Cryptosporidium hominis: 1,821 (11 %)
and 3,254 (12 %); Entamoeba histolytica: 2,245 (13 %) and 5,305 (19 %);
Leishmania infantum: 2,702 (16 %) and 4,760 (17 %). Using our HMM-based
methodology and the largest created orthologous database, it was possible to
infer 13 orthologous groups which represent potential protozoan targets; these
were found because of our distant homology approach. We also provide the number
of species-specific, pair-to-pair and core groups from such analyses, depicted in
Venn diagrams. CONCLUSIONS: The orthologous databases generated by our HMM-based
methodology provide a broader dataset, with larger amounts of orthologous groups
when compared to the original databases used as input. Those may be used for
several homology inference analyses, annotation tasks and protozoan targets
identification.
PMID- 26416525
TI - Bacterial contamination of propofol vials used in operating rooms of a third
level hospital.
AB - We found a 6.1% bacterial contamination rate among 198 propofol vials collected
after clinical use in 12 operating rooms of a high-complexity hospital in Cali,
Colombia. Some propofol vials were used for extended periods (up to 72 hours),
and only 26.1% of vials were punctured once. Median time of use, although not
statistically significant, was higher in positive samples (7.2 vs 3.5 hours, P =
.08). Education on the topic should stress that vials are single-patient use and
must be immediately discarded after use.
PMID- 26416526
TI - Integrated measures for prevention of invasive Candida infections in preterm
infants in a Chinese neonatal intensive care unit.
AB - BACKGROUND: The increasing incidence of invasive Candida infections (ICIs) in
preterm infants in the neonatal intensive care unit (NICU) of Xinhua Hospital
aroused our concern. We undertook a retrospective study to evaluate the efficacy
of different preventive measures for ICI in preterm infants. METHODS: Preterm
infants with gestational age (GA) <33 weeks admitted between 2010 and 2013 were
divided into 3 groups according to the preventive measures applied in different
periods: the control group (CG), fluconazole group (FG), and integrated measures
group (IMG). We analyzed the incidence of ICI and distribution of fungal
pathogens in these 3 groups, and also evaluated the efficiency of various
measures in preventing ICIs in preterm infants. RESULTS: The study sample
comprised 261 preterm infants born at <33 weeks GA, including 94 in the CG, 99 in
the FG, and 68 in the IMG. The differences among the groups were not significant
at baseline. ICI developed in 41 of the 261 infants (15.7%). The incidence of ICI
varied significantly among the groups: 22.3% in the CG (21/94), 18.2% in the FG
(18/99), and only 2.9% in the IMG (2/68) (P = .003). ICI was less frequent in the
IMG compared with the CG (P <.001) and the FG (P = .003). CONCLUSIONS: The
integrated measures approach is meaningful for the prevention of ICIs in preterm
infants in NICUs with many patients but inadequate medical resources in some
developing countries.
PMID- 26416527
TI - Effect of geographic region and seasonality on Clostridium difficile incidence
and hospital mortality.
PMID- 26416528
TI - Disinfection of reusable elastomeric respirators by health care workers: A
feasibility study and development of standard operating procedure.
PMID- 26416529
TI - Transformation priming helps to disambiguate sudden changes of sensory inputs.
AB - Retinal input is riddled with abrupt transients due to self-motion, changes in
illumination, object-motion, etc. Our visual system must correctly interpret each
of these changes to keep visual perception consistent and sensitive. This poses
an enormous challenge, as many transients are highly ambiguous in that they are
consistent with many alternative physical transformations. Here we investigated
inter-trial effects in three situations with sudden and ambiguous transients,
each presenting two alternative appearances (rotation-reversing structure-from
motion, polarity-reversing shape-from-shading, and streaming-bouncing object
collisions). In every situation, we observed priming of transformations as the
outcome perceived in earlier trials tended to repeat in subsequent trials and
this repetition was contingent on perceptual experience. The observed priming was
specific to transformations and did not originate in priming of perceptual states
preceding a transient. Moreover, transformation priming was independent of
attention and specific to low level stimulus attributes. In summary, we show how
"transformation priors" and experience-driven updating of such priors helps to
disambiguate sudden changes of sensory inputs. We discuss how dynamic
transformation priors can be instantiated as "transition energies" in an "energy
landscape" model of the visual perception.
PMID- 26416530
TI - Development and validation of UPLC and LC-MS/MS methods for the simultaneous
determination of anti-obesity drugs in foods and dietary supplements.
AB - Recently, the number of the cases in which weight loss products have been sold
with illegal adulterants has increased, as awareness of the problems of obesity
grows. In this study, we developed simultaneous analysis methods to rapidly and
accurately identify ingredients illegally mixed with foods and dietary
supplements. Twenty-three anti-obesity drugs in foods and dietary supplements
were determined by developed and validated UPLC and LC-MS/MS methods. The UPLC
method were validated for the LOD and LOQ in the ranges 0.05-3.0 and 0.2-10.0
MUg/mL, respectively. The determination coefficient was over 0.999, precision was
<6.2 %, and the accuracy was 80.8-103.9 %. The mean recoveries ranged from 80.3
to 109.3 % and RSD of stability was less than 2.1 %. The determination of the 23
anti-obesity drugs was accomplished by electrospray ionization LC-MS/MS using
multiple reaction monitoring (MRM). The LODs and LOQs were in the ranges 0.03-7.5
and 0.09-30.0 ng/mL, respectively. The LC-MS/MS method was validated for
linearity (r(2) > 0.99), precision (RSD < 10.7 %), accuracy (94.1-109.1 %),
recovery (80.5-113.5 %), and the RSD of stability was <7.8 %. Using the newly
developed and validated method, 193 samples were tested, and 55 were found to be
adulterated.
PMID- 26416531
TI - Structure of Liver Receptor Homolog-1 (NR5A2) with PIP3 hormone bound in the
ligand binding pocket.
AB - The nuclear receptor LRH-1 (Liver Receptor Homolog-1, NR5A2) is a transcription
factor that regulates gene expression programs critical for many aspects of
metabolism and reproduction. Although LRH-1 is able to bind phospholipids, it is
still considered an orphan nuclear receptor (NR) with an unknown regulatory
hormone. Our prior cellular and structural studies demonstrated that the
signaling phosphatidylinositols PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3) bind and
regulate SF-1 (Steroidogenic Factor-1, NR5A1), a close homolog of LRH-1. Here, we
describe the crystal structure of human LRH-1 ligand binding domain (LBD) bound
by PIP3 - the first phospholipid with a head group endogenous to mammals. We show
that the phospholipid hormone binds LRH-1 with high affinity, stabilizing the
receptor LBD. While the hydrophobic PIP3 tails (C16/C16) are buried inside the
LRH-1 ligand binding pocket, the negatively charged PIP3 head group is presented
on the receptor surface, similar to the phosphatidylinositol binding mode
observed in the PIP3-SF-1 structure. Thus, data presented in this work reinforce
our earlier findings demonstrating that signaling phosphatidylinositols regulate
the NR5A receptors LRH-1 and SF-1.
PMID- 26416532
TI - Numerical geometry of map and model assessment.
AB - We are describing best practices and assessment strategies for the atomic
interpretation of cryo-electron microscopy (cryo-EM) maps. Multiscale numerical
geometry strategies in the Situs package and in secondary structure detection
software are currently evolving due to the recent increases in cryo-EM
resolution. Criteria that aim to predict the accuracy of fitted atomic models at
low (worse than 8A) and medium (4-8 A) resolutions remain challenging. However, a
high level of confidence in atomic models can be achieved by combining such
criteria. The observed errors are due to map-model discrepancies and due to the
effect of imperfect global docking strategies. Extending the earlier motion
capture approach developed for flexible fitting, we use simulated fiducials
(pseudoatoms) at varying levels of coarse-graining to track the local drift of
structural features. We compare three tracking approaches: naive vector
quantization, a smoothly deformable model, and a tessellation of the structure
into rigid Voronoi cells, which are fitted using a multi-fragment refinement
approach. The lowest error is an upper bound for the (small) discrepancy between
the crystal structure and the EM map due to different conditions in their
structure determination. When internal features such as secondary structures are
visible in medium-resolution EM maps, it is possible to extend the idea of point
based fiducials to more complex geometric representations such as helical axes,
strands, and skeletons. We propose quantitative strategies to assess map-model
pairs when such secondary structure patterns are prominent.
PMID- 26416533
TI - Crystal structure of halogenase PltA from the pyoluteorin biosynthetic pathway.
AB - Pyoluteorin is an antifungal agent composed of a 4,5-dichlorinated pyrrole group
linked to a resorcinol moiety. The pyoluteorin biosynthetic gene cluster in
Pseudomonas fluorescens Pf-5 encodes the halogenase PltA, which has been
previously demonstrated to perform both chlorinations in vitro. PltA selectively
accepts as a substrate a pyrrole moiety covalently tethered to a nonribosomal
peptide thiolation domain PltL (pyrrolyl-S-PltL) for FAD-dependent di
chlorination, yielding 4,5-dichloropyrrolyl-S-PltL. We report a 2.75 A-resolution
crystal structure of PltA in complex with FAD and chloride. PltA is a dimeric
enzyme, containing a flavin-binding fold conserved in flavin-dependent
halogenases and monooxygenases, and an additional unique helical region at the C
terminus. This C-terminal region blocks a putative substrate-binding cleft,
suggesting that a conformational change involving repositioning of this region is
necessary to allow binding of the pyrrolyl-S-PltL substrate for its
dichlorination by PltA.
PMID- 26416534
TI - Population Pharmacokinetic Analysis of Lanreotide Autogel/Depot in the Treatment
of Neuroendocrine Tumors: Pooled Analysis of Four Clinical Trials.
AB - BACKGROUND AND OBJECTIVES: Lanreotide Autogel (lanreotide Depot in the USA) has
demonstrated anti-tumor activity and control of the symptoms associated with
hormone hypersecretion in patients with neuroendocrine tumors. The objectives of
this study were to describe the pharmacokinetics of lanreotide Autogel
administered 4-weekly by deep subcutaneous injections of 60, 90, or 120 mg in
patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), to
quantify the magnitude of inter-patient variability (IPV), and to identify those
patient characteristics that impact on pharmacokinetics. METHODS: Analyses were
based on pooled data from clinical trials. A total of 1541 serum concentrations
from 290 patients were analyzed simultaneously by the population approach using
NONMEM version 7.2. Covariates evaluated included demographics, renal and hepatic
function markers, and disease-related parameters. RESULTS: Serum profiles were
described by a one-compartment disposition model in which the absorption process
was characterized by two parallel pathways following first- and zero-order
kinetics. The estimated apparent volume of distribution was 18.3 L. The estimated
apparent total serum clearance for a typical 74 kg patient was 513 L/day,
representing a substantial difference in clearance in this population of patients
with respect to healthy volunteers that could not be explained by any of the
covariates tested. Body weight was the only covariate to show a statistically
significant effect on the pharmacokinetic profile, but due to the overlap between
the pharmacokinetic profiles of patients with lower or higher body weights the
effect of body weight on clearance was not considered clinically relevant. The
IPV was low for clearance (27%) and moderate to high for volume of distribution
(150%) and the absorption constant (61%). CONCLUSIONS: Using two mechanisms of
absorption, the pharmacokinetics of lanreotide Autogel were well-described in
patients with GEP-NET. None of the patient characteristics tested were of
clinical relevance to potential dose adjustment in clinical practice.
PMID- 26416535
TI - Interactions of Non-Phosphorous Glycerolipids with DNA: Energetics, Molecular
Docking and Topoisomerase I Attenuation.
AB - The phosphorus-containing glycerolipid based antitumor drugs (edelfosine as a
prototype) are currently in clinical trials. To avoid the use of potentially
harmful phosphoric reagents in the preparation of biologically active
glycerolipids, and to obtain the compounds without the phosphoester bond
cleavable inside the cells, we developed the synthesis of non-phosphorous
glycerolipids (NPGLs) with neutral or cationic polar 'heads'. In this study, we
analyzed the ability of novel NPGLs L1-L5 to interact with duplex DNA and
interfere with the DNA modifying enzyme topoisomerase I (topo I). In cell-free
systems, NPGLs formed highly affine complexes with DNA. Molecular docking
revealed that NPGLs fitted very well into the DNA minor groove. Compounds L2
(with two long hydrophobic 'tails') and L4 (with ethylimidazolium cationic
group), the most affine DNA binders, showed the best calculated energies of
complex formation with DNA and topo I. The models demonstrated the binding of
NPGLs to the topo I site known for interaction with conventional inhibitors. Each
NPGL attenuated the topo I mediated unwinding of supercoiled DNA. Again, L2 and,
to a lesser extent, L4 were the most potent topo I inhibitors. Thus, NPGLs with
polar 'heads' emerge as a new class of DNA ligands and interfacial topo I
antagonists.
PMID- 26416536
TI - Multiple sclerosis: smoking in patients with multiple sclerosis--is it ever too
late to quit?
PMID- 26416537
TI - Alzheimer disease: APOE*epsilon4-associated increase in AD risk linked to
phospholipid dysregulation.
PMID- 26416538
TI - Alzheimer disease: possible prion-like transmission of AD-like pathology in
humans.
PMID- 26416540
TI - Alzheimer disease: neurogranin in the CSF signals early Alzheimer disease and
predicts disease progression.
PMID- 26416539
TI - CAP--advancing the evaluation of preclinical Alzheimer disease treatments.
AB - If we are to find treatments to postpone, reduce the risk of, or completely
prevent the clinical onset of Alzheimer disease (AD), we need faster methods to
evaluate promising preclinical AD treatments, new ways to work together in
support of common goals, and a determination to expedite the initiation and
performance of preclinical AD trials. In this article, we note some of the
current challenges, opportunities and emerging strategies in preclinical AD
treatment. We describe the Collaboration for Alzheimer's Prevention (CAP)-a
convening, harmonizing and consensus-building initiative to help stakeholders
advance AD prevention research with rigour, care and maximal impact-and we
demonstrate the impact of CAP on the goals and design of new preclinical AD
trials.
PMID- 26416541
TI - Prevalence of Cardiovascular Disease and Cardiac Symptoms: Left and Right
Ventricular Function in Adults With Osteogenesis Imperfecta.
AB - BACKGROUND: Osteogenesis imperfecta (OI), also known as brittle bone disease or
Lobstein syndrome, is a congenital bone disorder characterized by brittle bones
that are prone to fracture. People with OI are born with defective connective
tissue in most cases secondary to a deficiency of type-I collagen, which
represents approximately 75% of total collagen in the adult myocardium. The
purpose of our study was to assess the prevalence of cardiomyopathy,
electrocardiogram (ECG) abnormalities, and cardiovascular symptoms among patients
with OI. METHODS: We studied 99 adults with OI from the national OI registry in
Norway. Patients were divided into type I, III, and IV, and 52 control subjects.
History and physical examination, ECG, and echocardiographic parameters of left
ventricular (LV) and right ventricular (RV) systolic and diastolic function were
obtained. RESULTS: ECG abnormalities and cardiac symptoms were more common among
patients with OI. RV and LV systolic peak velocity were significantly lower and
diastolic mitral tricuspid valve wave and early diastolic tissue Doppler velocity
ratio increased in the OI group compared with the control subjects; 5.7 +/- 1.2
vs 6.3 +/- 1.2 cm/s (P < 0.05) and 8 +/- 1.8 vs 9.5 +/- 1.4 cm/s (P < 0.05) and
9.8 +/- 2.6 vs 7.4 +/- 2.0 (P < 0.05) and 8.6 +/- 3.3 vs 6.1 +/- 1.4,
respectively. In multivariate analysis OI was found to be an independent risk
factor for RV systolic and diastolic dysfunction. CONCLUSIONS: Cardiac symptoms
and ECG changes are common among patients with OI. Our study findings suggest RV
and LV systolic and diastolic function to be impaired in patients with OI
compared with normal individuals. In multivariate analysis, however, OI was an
independent predictor only of reduced RV systolic and diastolic function.
PMID- 26416542
TI - A Novel Inherited Mutation in PRKAR1A Abrogates PreRNA Splicing in a Carney
Complex Family.
AB - BACKGROUND: Carney complex (CNC) is an autosomal dominant inherited disease,
characterized by spotty skin pigmentation, cardiac and cutaneous myxomas, and
endocrine overactivity. We report on a Chinese CNC family with a novel mutation
in the protein kinase A regulatory subunit 1 (PRKAR1A) gene. METHODS: Target
exome sequencing was performed to identify the mutation of PRKAR1A in 2 members
of the CNC family. RESULTS: The proband was a young man with typical CNC,
including pigmentation, cutaneous myxomas, cardiac myxoma, Sertoli cell tumour of
his left testis, and multiple hypoechoic thyroid nodules. His mother also had CNC
with skin pigmentation, cutaneous myxomas, and a cardiac myxoma. Target-exome
capture analysis revealed that the proband and the mother carried a novel
heterozygous mutation in the exon 6 splicing donor site of PRKAR1A. Sequencing
analysis of myxoma messenger RNA revealed that the mutation abrogated exon 6
preRNA splicing, leading to a frameshift starting at Valine 185 and premature
translation termination in intron 6. The truncated enzyme lacks the functional
cyclic adenosine monophosphate (cAMP) binding domain at the C-terminus, causing
PRKAR1A haploinsufficiency. CONCLUSIONS: In this study we report on a novel
splicing mutation in the PRKAR1A gene that adds to the genetic heterogeneity of
CNC.
PMID- 26416543
TI - Mortality changes after grants from the Global Fund to Fight AIDS, tuberculosis
and malaria: an econometric analysis from 1995 to 2010.
AB - BACKGROUND: Since its founding in 2002, the Global Fund to Fight AIDS,
Tuberculosis, and Malaria (Global Fund) has become the dominant multilateral
health financier in low- and middle-income countries. The health impact of the
Global Fund remains unknown because existing evaluations measure intermediate
outcomes or do not account for preexisting and counterfactual trends. METHODS: We
conducted an econometric analysis of data from all countries eligible to receive
Global Fund grants from 1995 to 2010, prior to and during the Global Fund's
activities. We analyzed three outcomes: all-cause adult (15-59 years), all-cause
under-five, and malaria-specific under-five mortality. Our main exposure was a
continuous longitudinal measure of Global Fund disbursements per capita. We used
panel fixed effect regressions, and analyzed mortality trends controlling for
health spending, health worker density (a measure of health system capacity),
gross domestic product, urbanization, and country fixed-effects. RESULTS AND
DISCUSSION: We find that following Global Fund disbursements, adult mortality
rate declined by 1.4 % per year faster with every $10 per capita increase in
disbursements (p = 0.005). Similarly, malaria-specific under-five mortality
declined by 6.9 % per year faster (p = 0.033) with every $10 high per capita
Global Fund disbursements. However, we find no association between Global Fund
support and all-cause under-five mortality. These findings were consistent after
subanalyses by baseline HIV prevalence, adjusting for effects of concurrent
health aid from other donors, and varying time lags between funding and mortality
changes. CONCLUSIONS: Grants from the Global Fund are closely related to
accelerated reductions in all-cause adult mortality and malaria-specific under
five mortality. However, up to 2010 the Global Fund has not measurably
contributed to reducing all-cause under-five mortality.
PMID- 26416544
TI - A homozygous loss-of-function mutation in inositol monophosphatase 1 (IMPA1)
causes severe intellectual disability.
AB - The genetic basis of intellectual disability (ID) is extremely heterogeneous and
relatively little is known about the role of autosomal recessive traits. In a
field study performed in a highly inbred area of Northeastern Brazil, we
identified and investigated a large consanguineous family with nine adult members
affected by severe ID associated with disruptive behavior. The Genome-Wide Human
SNP Array 6.0 microarray was used to determine regions of homozygosity by descent
from three affected and one normal family member. Whole-exome sequencing (WES)
was performed in one affected patient using the Nextera Rapid-Capture Exome kit
and Illumina HiSeq2500 system to identify the causative mutation. Potentially
deleterious variants detected in regions of homozygosity by descent and not
present in either 59 723 unrelated individuals from the Exome Aggregation
Consortium (Browser) or 1484 Brazilians were subject to further scrutiny and
segregation analysis by Sanger sequencing. Homozygosity-by-descent analysis
disclosed a 20.7-Mb candidate region at 8q12.3-q21.2 (lod score: 3.11). WES
identified a homozygous deleterious variant in inositol monophosphatase 1 (IMPA1)
(NM_005536), consisting of a 5-bp duplication (c.489_493dupGGGCT; chr8:
82,583,247; GRCh37/hg19) leading to a frameshift and a premature stop codon
(p.Ser165Trpfs*10) that cosegregated with the disease in 26 genotyped family
members. The IMPA1 gene product is responsible for the final step of
biotransformation of inositol triphosphate and diacylglycerol, two second
messengers. Despite its many physiological functions, no clinical phenotype has
been assigned to this gene dysfunction to date. Additionally, IMPA1 is the main
target of lithium, a drug that is at the forefront of treatment for bipolar
disorder.
PMID- 26416545
TI - Dimensional depression severity in women with major depression and post-traumatic
stress disorder correlates with fronto-amygdalar hypoconnectivty.
AB - Depressive symptoms are common in multiple psychiatric disorders and are frequent
sequelae of trauma. A dimensional conceptualization of depression suggests that
symptoms should be associated with a continuum of deficits in specific neural
circuits. However, most prior investigations of abnormalities in functional
connectivity have typically focused on a single diagnostic category using
hypothesis-driven seed-based analyses. Here, using a sample of 105 adult female
participants from three diagnostic groups (healthy controls, n=17; major
depression, n=38; and post-traumatic stress disorder, n=50), we examine the
dimensional relationship between resting-state functional dysconnectivity and
severity of depressive symptoms across diagnostic categories using a data-driven
analysis (multivariate distance-based matrix regression). This connectome-wide
analysis identified foci of dysconnectivity associated with depression severity
in the bilateral amygdala. Follow-up seed analyses using subject-specific
amygdala segmentations revealed that depression severity was associated with
amygdalo-frontal hypo-connectivity in a network of regions including bilateral
dorsolateral prefrontal cortex, anterior cingulate and anterior insula. In
contrast, anxiety was associated with elevated connectivity between the amygdala
and the ventromedial prefrontal cortex. Taken together, these results emphasize
the centrality of the amygdala in the pathophysiology of depressive symptoms, and
suggest that dissociable patterns of amygdalo-frontal dysconnectivity are a
critical neurobiological feature across clinical diagnostic categories.
PMID- 26416547
TI - Fixation times in evolutionary games with the Moran and Fermi processes.
AB - We combined the standard Moran and Fermi process into a mixed process with two
strategies C (co-operation) and D (defection). In a well-mixed population of size
N+M, N individuals have the same update mechanism as that of Moran process, while
the other M individuals have the same update mechanism as that of Fermi process.
We obtain the balance equations of the conditional fixation time and
unconditional fixation time. What these equations are doing is to make numerical
sense for all the figures. We find that the expectation values of conditional
fixation times of a single co-operator are smaller than the average values of the
standard Moran and Fermi process. In addition, the conditional fixation time of a
single co-operator with update rule of Moran is larger than that of Fermi when
the intensity of selection is sufficiently small. The simulation results show
that the unconditional fixation time of a co-operator who obtains more
information is smaller. In addition, the larger the difference of individuals'
payoff, the smaller the unconditional fixation time.
PMID- 26416546
TI - Cell-specific abnormalities of glutamate transporters in schizophrenia: sick
astrocytes and compensating relay neurons?
AB - Excitatory amino-acid transporters (EAATs) bind and transport glutamate, limiting
spillover from synapses due to their dense perisynaptic expression primarily on
astroglia. Converging evidence suggests that abnormalities in the astroglial
glutamate transporter localization and function may underlie a disease mechanism
with pathological glutamate spillover as well as alterations in the kinetics of
perisynaptic glutamate buffering and uptake contributing to dysfunction of
thalamo-cortical circuits in schizophrenia. We explored this hypothesis by
performing cell- and region-level studies of EAAT1 and EAAT2 expression in the
mediodorsal nucleus of the thalamus in an elderly cohort of subjects with
schizophrenia. We found decreased protein expression for the typically astroglial
localized glutamate transporters in the mediodorsal and ventral tier nuclei. We
next used laser-capture microdissection and quantitative polymerase chain
reaction to assess cell-level expression of the transporters and their splice
variants. In the mediodorsal nucleus, we found lower expression of transporter
transcripts in a population of cells enriched for astrocytes, and higher
expression of transporter transcripts in a population of cells enriched for relay
neurons. We confirmed expression of transporter protein in neurons in
schizophrenia using dual-label immunofluorescence. Finally, the pattern of
transporter mRNA and protein expression in rodents treated for 9 months with
antipsychotic medication suggests that our findings are not due to the effects of
antipsychotic treatment. We found a compensatory increase in transporter
expression in neurons that might be secondary to a loss of transporter expression
in astrocytes. These changes suggest a profound abnormality in astrocyte
functions that support, nourish and maintain neuronal fidelity and synaptic
activity.
PMID- 26416548
TI - Preimplantation death of xenomitochondrial mouse embryo harbouring bovine
mitochondria.
AB - Mitochondria, cellular organelles playing essential roles in eukaryotic cell
metabolism, are thought to have evolved from bacteria. The organization of mtDNA
is remarkably uniform across species, reflecting its vital and conserved role in
oxidative phosphorylation (OXPHOS). Our objectives were to evaluate the
compatibility of xenogeneic mitochondria in the development of preimplantation
embryos in mammals. Mouse embryos harbouring bovine mitochondria (mtB-M embryos)
were prepared by the cell-fusion technique employing the haemagglutinating virus
of Japan (HVJ). The mtB-M embryos showed developmental delay at embryonic days
(E) 3.5 after insemination. Furthermore, none of the mtB-M embryos could implant
into the maternal uterus after embryo transfer, whereas control mouse embryos
into which mitochondria from another mouse had been transferred developed as well
as did non-manipulated embryos. When we performed quantitative PCR (qPCR) of
mouse and bovine ND5, we found that the mtB-M embryos contained 8.3% of bovine
mitochondria at the blastocyst stage. Thus, contamination with mitochondria from
another species induces embryonic lethality prior to implantation into the
maternal uterus. The heteroplasmic state of these xenogeneic mitochondria could
have detrimental effects on preimplantation development, leading to preservation
of species-specific mitochondrial integrity in mammals.
PMID- 26416549
TI - Enhancement of Mechanical Properties and Testing of Nitinol Stents in Cerebral
Aneurysm Simulation Models.
AB - Stents are promising medical devices widely used in the prevention of cerebral
aneurysm rupture. As the performance of stents depends on their mechanical
properties and cell configuration, the aim of this study was to optimize the
stent design and test the hemodynamic properties by using computational solid
mechanics and computational fluid dynamics. In order to test their performance,
computer-based cerebral aneurysm models that mimic the conditions present after
implantation into the human brain were tested. The strut configuration selected
was the closed-cell type, and nitinol was chosen as the material for stent
manufacture because the innate characteristics of this material increase stent
flexibility. Three ideal sample stent types with different cell configurations
were manufactured. Computational solid mechanics analysis of the sample stents
showed over 30% difference in flexibility between stents. Furthermore, using a
cerebral aneurysm model simulation, we found that the stents eased the
hemodynamic factors of the cerebral aneurysm and lessened the flow velocity
influx into the sac. A decrease in flow velocity led to a 50-60% reduction in
wall shear stress, which is expected to prevent aneurysm rupture under clinical
conditions. Stent design optimization was carried out by simulation and
electropolishing. Corrosion resistance and surface roughness were evaluated after
electropolishing performed under variable conditions, but 40 V and 10 s were the
most optimal.
PMID- 26416550
TI - A new synthesis of carbon encapsulated Fe5C2 nanoparticles for high-temperature
Fischer-Tropsch synthesis.
AB - Using a simple thermal treatment under a CO flow, uniform micrometer-sized iron
oxalate dihydrate cubes prepared by hydrothermal reaction were transformed into
Fe5C2@C nanoparticles to form a mesoporous framework; the final structure was
successfully applied to the high-temperature Fischer-Tropsch reaction and it
showed high activity (CO conversion = 96%, FTY = 1.5 * 10(-4) molCO gFe(-1) s(
1)) and stability.
PMID- 26416551
TI - Radical 1,2-aryl migration in alpha,alpha-diaryl allylic alcohols toward beta
silyl ketones.
AB - A copper-catalyzed radical 1,2-aryl migration in alpha,alpha-diaryl allylic
alcohols is developed, leading to beta-silyl carbonyl compounds in moderate to
good yields. The migration of aryls with lower aromaticity is favored. This
procedure features the employment of silanes as commercially available materials.
PMID- 26416552
TI - Improving Caregivers' Perceptions Regarding Patient Goals of Care/End-of-Life
Issues for the Multidisciplinary Critical Care Team.
AB - OBJECTIVE: With population aging and growth, use of critical care medicine at the
end of life continues to rise, while many critical care providers are not
adequately trained regarding goals of care/end-of-life (GOC/EOL) issues. A
multidisciplinary intensive care unit (ICU) team intervention regarding GOC/EOL
communication will enhance the clinical abilities of all critical care providers
when discussing GOC/EOL issues and increase ICU staff comfort level while
improving transitions for patients to a comfort care approach. DESIGN: This study
was a preintervention/postintervention survey evaluation. SETTING: This study was
conducted at an academic tertiary surgical burn trauma ICU. POPULATION: The
intervention was provided to nursing, ancillary staff, house staff, and attending
physicians. INTERVENTION: An initial survey was circulated among the critical
care staff for baseline expectations, satisfaction, and understanding of GOC/EOL
care. A robust intervention was begun including the creation of a
multidisciplinary GOC/EOL team, communication tools for providers, patient-family
pamphlets, standardized EOL order sets, and formalized didactic sessions.
Subsequently, the same survey was circulated and compared to baseline data.
MEASUREMENTS: Preintervention/postintervention survey data were reviewed and
statistically analyzed. MAIN RESULTS: Our survey response rate for
preintervention/postintervention was 50.4% and 36.1%, respectively. The
intervention generated heightened interest in improving family communication and
provided focal direction to foster this growth. Based on the serial surveys
regarding our intervention, statistically significant staff improvements were
seen in "work stress" (P = .04), "EOL information" (P = .006), and "space
allotment" (P = .001). Improved congruence of families and health care providers
regarding decision over intensity of care was also noted. CONCLUSION: We created
a novel unit-based multidisciplinary program for improved EOL/GOC approaches in
the critical care setting. A similarly formatted program could be adapted by
other ICUs. Benefits of such a program include improving caregivers' perceptions
regarding EOL/GOC issues and fostering critical care team growth.
PMID- 26416553
TI - The impact of Indonesian peatland degradation on downstream marine ecosystems and
the global carbon cycle.
AB - Tropical peatlands are among the most space-efficient stores of carbon on Earth
containing approximately 89 Gt C. Of this, 57 Gt (65%) are stored in Indonesian
peatlands. Large-scale exploitation of land, including deforestation and drainage
for the establishment of oil palm plantations, is changing the carbon balance of
Indonesian peatlands, turning them from a natural sink to a source via outgassing
of CO2 to the atmosphere and leakage of dissolved organic carbon (DOC) into the
coastal ocean. The impacts of this perturbation to the coastal environment and at
the global scale are largely unknown. Here, we evaluate the downstream effects of
released Indonesian peat carbon on coastal ecosystems and on the global carbon
cycle. We use a biogeochemical box model in combination with novel and literature
observations to investigate the impact of different carbon emission scenarios on
the combined ocean-atmosphere system. The release of all carbon stored in the
Indonesian peat pool, considered as a worst-case scenario, will increase
atmospheric pCO2 by 8 ppm to 15 ppm within the next 200 years. The expected
impact on the Java Sea ecosystems is most significant on the short term (over a
few hundred years) and is characterized by an increase of 3.3% in phytoplankton,
32% in seagrass biomass, and 5% decrease in coral biomass. On the long term,
however, the coastal ecosystems will recover to reach near pre-excursion
conditions. Our results suggest that the ultimate fate of the peat carbon is in
the deep ocean with 69% of it landing in the deep DIC pool after 1000 years, but
the effects on the global ocean carbonate chemistry will be marginal.
PMID- 26416554
TI - PTBP1 and PTBP2 impaired autoregulation of SRSF3 in cancer cells.
AB - Splicing factors are key players in the regulation of alternative splicing of pre
mRNAs. Overexpression of splicing factors, including SRSF3, has been strongly
linked with oncogenesis. However, the mechanisms behind their overexpression
remain largely unclear. Autoregulation is a common mechanism to maintain relative
stable expression levels of splicing factors in cells. SRSF3 regulates its own
expression by enhancing the inclusion of an alternative exon 4 with an in-frame
stop codon. We found that the inclusion of SRSF3 exon 4 is impaired in oral
squamous cell carcinoma (OSCC) cells. PTBP1 and PTBP2 bind to an exonic splicing
suppressor in exon 4 and inhibit its inclusion, which results in overexpression
of full length functional SRSF3. Overexpression of SRSF3, in turn, promotes PTBP2
expression. Our results suggest a novel mechanism for the overexpression of
oncogenic splicing factor via impairing autoregulation in cancer cells.
PMID- 26416555
TI - Dynamic development of public attitudes towards science policymaking.
AB - Understanding the heterogeneity of mechanisms that form public attitudes towards
science and technology policymaking is essential to the establishment of an
effective public engagement platform. Using the 2011 public opinion survey data
from Japan (n = 6,136), I divided the general public into three categories: the
Attentive public, who are willing to actively engage with science and technology
policymaking dialogue; the Interested public, who have moderate interest in
science and technology but rely on experts for policy decisions; and the Residual
public, who have minimal interest in science and technology. On the basis of the
results of multivariate regression analysis, I have identified several key
predispositions towards science and technology and other socio-demographic
characteristics that influence the shift of individuals from one category of the
general public to another. The findings provide a foundation for understanding
how to induce more accountable, evidence-based science and technology
policymaking.
PMID- 26416556
TI - The role of shear in crystallization kinetics: From suppression to enhancement.
AB - In many technical applications crystallization proceeds in the presence of
stresses and flows, hence the importance to understand the crystallization
mechanism in simple situations. We employ molecular dynamics simulations to study
the crystallization kinetics of a nearly hard sphere liquid that is weakly
sheared. We demonstrate that shear flow both enhances and suppresses the
crystallization kinetics of hard spheres. The effect of shear depends on the
quiescent mechanism: suppression in the activated regime and enhancement in the
diffusion-limited regime for small strain rates. At higher strain rates
crystallization again becomes an activated process even at densities close to the
glass transition.
PMID- 26416557
TI - An efficient thermostable organophosphate hydrolase and its application in
pesticide decontamination.
AB - In vitro evolution of enzymes represents a powerful device to evolve new or to
improve weak enzymatic functions. In the present work a semi-rational engineering
approach has been used to design an efficient and thermostable organophosphate
hydrolase, starting from a lactonase scaffold (SsoPox from Sulfolobus
solfataricus). In particular, by in vitro evolution of the SsoPox ancillary
promiscuous activity, the triple mutant C258L/I261F/W263A has been obtained
which, retaining its inherent stability, showed an enhancement of its hydrolytic
activity on paraoxon up to 300-fold, achieving absolute values of catalytic
efficiency up to 10(5) M(-1) s(-1). The kinetics and structural determinants of
this enhanced activity were thoroughly investigated and, in order to evaluate its
potential biotechnological applications, the mutant was tested in formulations of
different solvents (methanol or ethanol) or detergents (SDS or a commercial soap)
for the cleaning of pesticide-contaminated surfaces.
PMID- 26416558
TI - Plasma levels of OLFM4 in normals and patients with gastrointestinal cancer.
AB - Olfactomedin 4 (OLFM4) is a secreted glycoprotein predominantly expressed in bone
marrow and gastrointestinal tissues. Aberrant expression of OLFM4 has been shown
in several cancers. However, the clinical significance hereof is currently
controversial. OLFM4 has been proposed as a candidate biomarker of
gastrointestinal cancers. To address this, we developed monoclonal antibodies
against synthetic peptides representing various segments of OLFM4. We examined
expression of OLFM4 in epithelial cells by immunohistochemistry and found that
OLFM4 is highly expressed in proliferating benign epithelial cells and in some
carcinoma cells. We developed an Enzyme Linked Immunosorbent Assay for OLFM4 and
investigated whether plasma levels of OLFM4 reflect colorectal malignancies, but
were unable to see any such association. Instead, we observed two populations of
individuals with respect to OLFM4 levels in plasma, the majority with OLFM4 in
plasma between 0 and 0.1 MUg/ml, mean 0.028 MUg/ml while 10% of both normals and
patients with cancers had OLFM4 between 4 and 60 MUg/ml, mean 15 MUg/ml. The
levels were constant over time. The background for this high plasma level is not
known, but must be taken into account if OLFM4 is used as biomarker for GI
cancers.
PMID- 26416559
TI - Pseudomonas aeruginosa isolates and their antimicrobial susceptibility pattern
among catheterized patients at Jimma University Teaching Hospital, Jimma,
Ethiopia.
AB - BACKGROUND: Pseudomonas aeruginosa is among the most common bacterial pathogens
with wide spread distribution in health care settings. Despite advances in
medical and surgical care and introduction of wide variety of antimicrobial
agents, Pseudomonas aeruginosa continues to cause life threatening infection.
Thus, this study aims to isolate and determine antimicrobial susceptibility
patterns of Pseudomonas aeruginosa from catheterized patients with urinary tract
infection. RESULT: A cross-sectional study was conducted from January to May,
2013. Urine specimens of 73 catheterized patients who developed urinary tract
infection after catheterization were collected from sampling port of the
catheter. The urine samples were inoculated on MaConckey and blood agar plates,
and incubated at 37 degrees C for 24 h. The isolates were identified by
conventional microbiological tests. Antimicrobial susceptibility pattern was
determined by modified Kirby-Bauer disk diffusion method. From a total of 73
urine samples collected P. aeruginosa was isolated from 36 (49.32%) catheterized
patients; 17 (23.29%) males and 19 (26.03%) females. While all P. aeruginosa
isolates were found to be susceptible to Norfloxacin and Ciprofloxacin most
isolates were also susceptible to Gentamicin (86.12%). CONCLUSION: The result
shows higher prevalence of P. aeruginosa isolates among catheterized patients and
the isolates were susceptible to the antimicrobials studied. All P. aeruginosa
isolates were susceptible to Ciprofloxacin and Norfloxacin with some of the
isolates shown resistance to Gentamicin. While the susceptibility of the isolates
to the two fluoroquinolones is a good news for the prescribers their future
rational prescription and use should be the main focus.
PMID- 26416560
TI - In silico exploration of c-KIT inhibitors by pharmaco-informatics methodology:
pharmacophore modeling, 3D QSAR, docking studies, and virtual screening.
AB - c-KIT is a component of the platelet-derived growth factor receptor family,
classified as type-III receptor tyrosine kinase. c-KIT has been reported to be
involved in, small cell lung cancer, other malignant human cancers, and
inflammatory and autoimmune diseases associated with mast cells. Available c-KIT
inhibitors suffer from tribulations of growing resistance or cardiac toxicity. A
combined in silico pharmacophore and structure-based virtual screening was
performed to identify novel potential c-KIT inhibitors. In the present study,
five molecules from the ZINC database were retrieved as new potential c-KIT
inhibitors, using Schrodinger's Maestro 9.0 molecular modeling suite. An atom
featured 3D QSAR model was built using previously reported c-KIT inhibitors
containing the indolin-2-one scaffold. The developed 3D QSAR model ADHRR.24 was
found to be significant (R2 = 0.9378, Q2 = 0.7832) and instituted to be
sufficiently robust with good predictive accuracy, as confirmed through external
validation approaches, Y-randomization and GH approach [GH score 0.84 and
Enrichment factor (E) 4.964]. The present QSAR model was further validated for
the OECD principle 3, in that the applicability domain was calculated using a
"standardization approach." Molecular docking of the QSAR dataset molecules and
final ZINC hits were performed on the c-KIT receptor (PDB ID: 3G0E). Docking
interactions were in agreement with the developed 3D QSAR model. Model ADHRR.24
was explored for ligand-based virtual screening followed by in silico ADME
prediction studies. Five molecules from the ZINC database were obtained as
potential c-KIT inhibitors with high in -silico predicted activity and strong key
binding interactions with the c-KIT receptor.
PMID- 26416563
TI - Formulation of Nanoparticles Against TB--A Review.
AB - Tuberculosis is a major public health concern. The present article reviews the
current updates on the usage of nanoparticles against tuberculosis and recent
patents that could develop into novel therapeutics available to the clinical
armamentarium for the TB management. The drug delivery systems involving
nanoparticles are suitable against chronic diseases such as tuberculosis.
Polymers in many forms like liposomes, dendrimers, Nanoemulsions can be used as
synthetic and natural carriers for first line and second line drugs employed for
chemotherapy. Not only are the drugs sustainably released in organs and plasma,
but also their dosages as well as adverse effects have been reduced, the drug
interaction has increased and the drug resistant bacteria have been targeted. The
hurdles in the development of anti-tuberculosis have made Nano medicines to act
as a silver lining.
PMID- 26416561
TI - Alternative translation initiation codons for the plastid maturase MatK:
unraveling the pseudogene misconception in the Orchidaceae.
AB - BACKGROUND: The plastid maturase MatK has been implicated as a possible model for
the evolutionary "missing link" between prokaryotic and eukaryotic splicing
machinery. This evolutionary implication has sparked investigations concerning
the function of this unusual maturase. Intron targets of MatK activity suggest
that this is an essential enzyme for plastid function. The matK gene, however, is
described as a pseudogene in many photosynthetic orchid species due to presence
of premature stop codons in translations, and its high rate of nucleotide and
amino acid substitution. RESULTS: Sequence analysis of the matK gene from orchids
identified an out-of-frame alternative AUG initiation codon upstream from the
consensus initiation codon used for translation in other angiosperms. We
demonstrate translation from the alternative initiation codon generates a
conserved MatK reading frame. We confirm that MatK protein is expressed and
functions in sample orchids currently described as having a matK pseudogene using
immunodetection and reverse-transcription methods. We demonstrate using
phylogenetic analysis that this alternative initiation codon emerged de novo
within the Orchidaceae, with several reversal events at the basal lineage and
deep in orchid history. CONCLUSION: These findings suggest a novel evolutionary
shift for expression of matK in the Orchidaceae and support the function of MatK
as a group II intron maturase in the plastid genome of land plants including the
orchids.
PMID- 26416562
TI - Regulation of deoxynucleotide metabolism in cancer: novel mechanisms and
therapeutic implications.
AB - Regulation of intracellular deoxynucleoside triphosphate (dNTP) pool is critical
to genomic stability and cancer development. Imbalanced dNTP pools can lead to
enhanced mutagenesis and cell proliferation resulting in cancer development.
Therapeutic agents that target dNTP synthesis and metabolism are commonly used in
treatment of several types of cancer. Despite several studies, the molecular
mechanisms that regulate the intracellular dNTP levels and maintain their
homeostasis are not completely understood. The discovery of SAMHD1 as the first
mammalian dNTP triphosphohydrolase provided new insight into the mechanisms of
dNTP regulation. SAMHD1 maintains the homeostatic dNTP levels that regulate DNA
replication and damage repair. Recent progress indicates that gene mutations and
epigenetic mechanisms lead to downregulation of SAMHD1 activity or expression in
multiple cancers. Impaired SAMHD1 function can cause increased dNTP pool
resulting in genomic instability and cell-cycle progression, thereby facilitating
cancer cell proliferation. This review summarizes the latest advances in
understanding the importance of dNTP metabolism in cancer development and the
novel function of SAMHD1 in regulating this process.
PMID- 26416564
TI - Biomodulation of capecitabine by paclitaxel and carboplatin in advanced solid
tumors and adenocarcinoma of unknown primary.
AB - Paclitaxel and carboplatin upregulate thymidine phosphorylase and thus may
provide synergistic antitumor activity in combination with capecitabine (CTX).
We, therefore, performed a phase I/II study of CTX. In the phase I study,
patients with advanced solid tumors received carboplatin on day 1, paclitaxel on
days 1, 8, 15 and capecitabine orally twice a day on days 8-21, every 4 weeks.
Phase II patients with advanced adenocarcinoma of unknown primary (ACUP) were
treated at the maximal tolerable dose. The phase I study enrolled 29 patients
evaluable for dose limiting toxicity. The recommended phase II dose was
capecitabine 750 mg/m(2) bid, paclitaxel 60 mg/m(2)/week and carboplatin AUC of
6. There were 9 confirmed responses, 5 partial responses and disease
stabilization >3 months in 14 patients. The phase II study was prematurely
terminated at 25 patients due to cessation of funding. The objective response
rate was 32 % (95 % CI 0.15-0.54), the median progression-free survival 5.5
months (95 % CI 2.8-10.8 months) and the median overall survival 10.8 months (95
% CI 6.0-32.0 months). CTX demonstrated acceptable tolerability and antitumor
activity. At the recommended dose level in patients with ACUP, this regimen
showed encouraging preliminary activity.
PMID- 26416565
TI - Mechanism of action of ixabepilone and its interactions with the betaIII-tubulin
isotype.
AB - Ixabepilone (Ixempra, BMS-247550), a semisynthetic analog of epothilone B, is a
microtubule-targeted drug in clinical use for treatment of metastatic or locally
advanced breast cancer. Ixabepilone's binding and mechanism of action on
microtubules and their dynamics, as well as its interactions with isotypically
altered microtubules, both in vitro and in tumor cells, have not been described.
Microtubules are dynamic polymers of the protein tubulin that function in
mitosis, intracellular transport, cell proliferation, and migration. They
continually undergo dynamic instability, periods of slow growth and rapid
shortening that are crucial to these cell functions. We determined ixabepilone's
microtubule binding and polymerization effects in vitro and also determined its
effects on inhibition of dynamic instability in vitro and in cells, both with and
without removal of the betaIII isotype of tubulin. The betaIII isotype of tubulin
is associated with drug resistance and tumor aggressivity. We found that removal
(in vitro) and knockdown (in cells) of betaIII-tubulin led to increased
inhibition of microtubule dynamic instability by ixabepilone. Depletion of
betaIII-tubulin from MCF7 human breast cancer cells also induced increased
mitotic arrest by ixabepilone. Thus, betaIII-tubulin expression suppresses the
antitumor effects of ixabepilone, indicating that increased betaIII-tubulin may
be an important contributor to the development of resistance to ixabepilone.
PMID- 26416566
TI - Developing a mental health care plan in a low resource setting: the theory of
change approach.
AB - BACKGROUND: Scaling up mental healthcare through integration into primary care
remains the main strategy to address the extensive unmet mental health need in
low-income countries. For integrated care to achieve its goal, a clear
understanding of the organisational processes that can promote and hinder the
integration and delivery of mental health care is essential. Theory of Change
(ToC), a method employed in the planning, implementation and evaluation of
complex community initiatives, is an innovative approach that has the potential
to assist in the development of a comprehensive mental health care plan (MHCP),
which can inform the delivery of integrated care. We used the ToC approach to
develop a MHCP in a rural district in Ethiopia. The work was part of a cross
country study, the Programme for Improving Mental Health Care (PRIME) which
focuses on developing evidence on the integration of mental health in to primary
care. METHODS: An iterative ToC development process was undertaken involving
multiple workshops with stakeholders from diverse backgrounds that included
representatives from the community, faith and traditional healers, community
associations, non-governmental organisations, Zonal, Regional and Federal level
government offices, higher education institutions, social work and mental health
specialists (psychiatrists and psychiatric nurses). The objective of this study
is to report the process of implementing the ToC approach in developing mental
health care plan. RESULTS: A total of 46 persons participated in four ToC
workshops. Four critical path dimensions were identified: community, health
facility, administrative and higher level care organisation. The ToC participants
were actively engaged in the process and the ToC encouraged strong commitment
among participants. Key opportunities and barriers to implementation and how to
overcome these were suggested. During the workshops, a map incorporating the key
agreed outcomes and outcome indicators was developed and finalized later.
CONCLUSIONS: The ToC approach was found to be an important component in the
development of the MHCP and to encourage broad political support for the
integration of mental health services into primary care. The method may have
broader applicability in planning complex health interventions in low resource
settings.
PMID- 26416567
TI - Eighty percent of French sport winners in Olympic, World and Europeans
competitions have mutations in the hemochromatosis HFE gene.
AB - The HFE gene encodes a protein involved in iron homeostasis; individuals with
mutations in both alleles develop hemochromatosis. 27% of the French population
is heterozygous for mutations in this gene. We found that 80% of the French
athletes who won international competitions in rowing, Nordic skiing and judo
display mutations in one allele of HFE, thus demonstrating the existence of a
favourable phenotype linked to this heterozygosity.
PMID- 26416568
TI - The sensitive and selective adsorption of aromatic compounds with highly
crosslinked polymer nanoparticles.
AB - This study presents the preparation and characterization of a nanoscale Davankov
type hyper-crosslinked-polymer (HCP) as an adsorbent of benzene-ring-containing
dyes and organic pollutants. HCP nanoparticles post-crosslinked from a poly(DVB
co-VBC) precursor were synthesized in this study, possessing ultrahigh surface
area, hydrophobicity and stability. The as-synthesized Davankov-type HCP
exhibited a rapid and selective adsorption ability towards the benzene-ring
containing dyes due to its highly conjugated structure. Besides, for the first
time, the prepared HCP nanoparticles were adopted for the adsorption of nonpolar
organic pollutants by means of solid-phase microextraction (SPME). Owing to its
high hydrophobicity, diverse pore size distribution and highly conjugated
structure, a 10 MUm HCP coating exhibited excellent adsorption abilities towards
benzene-ring-containing polycyclic aromatic hydrocarbons (PAHs) and benzene
series compounds (benzene, toluene, ethylbenzene and o-xylene; abbreviated to
BTEX) and to highly hydrophobic long-chain n-alkanes. Finally, the HCP
nanoparticles-coated SPME fiber was applied to the simultaneous analysis of five
PAHs in environmental water samples and satisfactory recoveries were achieved.
The findings could provide a new benchmark for the exploitation of superb HCPs as
effective adsorbents for SPME or other adsorption applications.
PMID- 26416570
TI - The benefits/risks of treatment of non-severe hypertension in pregnancy and
choice of drug remain unanswered.
PMID- 26416572
TI - Precision Medicine for Pediatric Cancer.
AB - In a recent study, whole-exome and transcriptome sequencing identified
potentially actionable findings that led to effective treatments for some
children with advanced and rare cancers. The findings demonstrate that genomic
sequencing data can be effectively integrated into the clinical management of
pediatric patients.
PMID- 26416571
TI - Dose-response curve slope helps predict therapeutic potency and breadth of HIV
broadly neutralizing antibodies.
AB - A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable
potency, breadth and epitope diversity has rejuvenated interest in
immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values
(50 and 80% inhibitory concentrations) figure prominently into the selection of
clinical candidates; however, much higher therapeutic levels will be required to
reduce multiple logs of virus and impede escape. Here we predict bnAb potency at
therapeutic levels by analysing dose-response curve slopes, and show that slope
is independent of IC50/IC80 and specifically relates to bnAb epitope class. With
few exceptions, CD4-binding site and V3-glycan bnAbs exhibit slopes >1,
indicative of higher expected therapeutic effectiveness, whereas V2-glycan, gp41
membrane-proximal external region (MPER) and gp120-gp41 bnAbs exhibit less
favourable slopes <1. Our results indicate that slope is one major predictor of
both potency and breadth for bnAbs at clinically relevant concentrations, and may
better coordinate the relationship between bnAb epitope structure and therapeutic
expectations.
PMID- 26416573
TI - Pappa2 deletion in mice affects male but not female fertility.
AB - BACKGROUND: Recent studies have found associations between the gene encoding
pregnancy associated plasma protein-A2 (PAPP-A2), a protease of insulin-like
growth factor binding protein -5 (IGFBP-5), and measures of female reproductive
performance in cattle. The purpose of the present study was to test the effects
of Pappa2 deletion on reproduction in mice. FINDINGS: We measured the fertility
and offspring growth of Pappa2 deletion females, and also performed reciprocal
matings (i.e., deletion males mated to control females) to control for the
effects of offspring genotype. Ovarian and testicular IGFBP-5 levels were
measured by Western blotting. As expected, deletion of Pappa2 increased ovarian
IGFBP-5 levels. However, Pappa2 deletion in females had no effect on the interval
between pairing and the birth of the first litter, the interval between the
births of the first and second litters, or litter size. Offspring weight was
lower in the offspring of Pappa2 deletion females, but effects of similar
magnitude were observed in the offspring of Pappa2 deletion males, suggesting
that the effects were due to heterozygosity for the deletion in the offspring.
Pappa2 deletion in males had no effect on litter size or the interval between
pairing and the birth of the first litter. However, the interval between the
births of the first and second litters was significantly longer in deletion
males. CONCLUSIONS: Pappa2 deletion had no effect on female reproductive
performance. In contrast, Pappa2 deletion had subtle effects on male fertility,
although the underlying mechanism remains to be elucidated.
PMID- 26416575
TI - Phytotoxicity and Cytotoxicity of Essential Oil from Leaves of Plectranthus
amboinicus, Carvacrol, and Thymol in Plant Bioassays.
AB - The essential oil of Plectranthus amboinicus and its chemotypes, carvacrol and
thymol, were evaluated on the germination and root and aerial growth of Lactuca
sativa and Sorghum bicolor and in acting on the cell cycle of meristematic root
cells of L. sativa. The main component found in the oil by analysis in gas
chromatography-mass spectrometry and gas chromatography flame ionization
detection was carvacrol (88.61% in area). At a concentration of 0.120% (w v(-1)),
the oil and its chemotypes retarded or inhibited the germination and decreased
root and aerial growth in monocot and dicot species used in the bioassays. In
addition, all substances caused changes in the cell cycle of the meristematic
cells of L. sativa, with chromosomal alterations occurring from the 0.015% (w v(
1)) concentration. The essential oil of P. amboinicus, carvacrol, and thymol have
potential for use as bioherbicides.
PMID- 26416576
TI - Function of polar glycerolipids in flower development in Arabidopsis thaliana.
AB - The flower lipidome is an unexplored frontier of plant lipid research as compared
with the major advances in photosynthetic or storage organs. However, ample
evidence from recent molecular biological studies suggests that lipids play
crucial roles in coordinating flower development rather than being an inert end
product of metabolism. This review summarizes the current understanding of the
function of glycerolipids in flower development in Arabidopsis thaliana.
PMID- 26416574
TI - Implementation of a Care Pathway for Primary Palliative Care in 5 research
clusters in Belgium: quasi-experimental study protocol and innovations in data
collection (pro-SPINOZA).
AB - BACKGROUND: Starting with early identification of palliative care patients by
general practitioners (GPs), the Care Pathway for Primary Palliative Care (CPPPC)
is believed to help primary health care workers to deliver patient- and family
centered care in the last year of life. The care pathway has been pilot-tested,
and will now be implemented in 5 Belgian regions: 2 Dutch-speaking regions, 2
French-speaking regions and the bilingual capital region of Brussels. The overall
aim of the CPPPC is to provide better quality of primary palliative care, and in
the end to reduce the hospital death rate. The aim of this article is to describe
the quantitative design and innovative data collection strategy used in the
evaluation of this complex intervention. METHODS/DESIGN: A quasi-experimental
stepped wedge cluster design is set up with the 5 regions being 5 non-randomized
clusters. The primary outcome is reduced hospital death rate per GPs' patient
population. Secondary outcomes are increased death at home and health care
consumption patterns suggesting high quality palliative care. Per research
cluster, GPs will be recruited via convenience sampling. These GPs -volunteering
to be involved will recruit people with reduced life expectancy and their
informal care givers. Health care consumption data in the last year of life,
available for all deceased people having lived in the research clusters in the
study period, will be used for comparison between patient populations of
participating GPs and patient populations of non-participating GPs. Description
of baseline characteristics of participating GPs and patients and monitoring of
the level of involvement by GPs, patients and informal care givers will happen
through regular, privacy-secured web-surveys. Web-survey data and health
consumption data are linked in a secure way, respecting Belgian privacy laws.
DISCUSSION: To evaluate this complex intervention, a quasi-experimental stepped
wedge cluster design has been set up. Context characteristics and involvement
level of participants are important parameters in evaluating complex
interventions. It is possible to securely link survey data with health
consumption data. By appealing to IT solutions we hope to be able to partly
reduce respondent burden, a known problem in palliative care research. TRIAL
REGISTRATION: ClinicalTrials.gov Identifier: NCT02266069.
PMID- 26416577
TI - Fatty acid transport proteins in disease: New insights from invertebrate models.
AB - The dysregulation of lipid metabolism has been implicated in various diseases,
including diabetes, cardiopathies, dermopathies, retinal and neurodegenerative
diseases. Mouse models have provided insights into lipid metabolism. However,
progress in the understanding of these pathologies is hampered by the
multiplicity of essential cellular processes and genes that modulate lipid
metabolism. Drosophila and Caenorhabditis elegans have emerged as simple genetic
models to improve our understanding of these metabolic diseases. Recent studies
have characterized fatty acid transport protein (fatp) mutants in Drosophila and
C. elegans, establishing new models of cardiomyopathy, retinal degeneration, fat
storage disease and dermopathies. These models have generated novel insights into
the physiological role of the Fatp protein family in vivo in multicellular
organisms, and are likely to contribute substantially to progress in
understanding the etiology of various metabolic disorders. Here, we describe and
discuss the mechanisms underlying invertebrate fatp mutant models in the light of
the current knowledge relating to FATPs and lipid disorders in vertebrates.
PMID- 26416578
TI - Lipid emulsions for parenteral nutrition in critical illness.
AB - Critical illness is a life-threatening multisystem process that can result in
significant morbidity and mortality. In most patients, critical illness is
preceded by a physiological deterioration, characterized by a catabolic state and
intense metabolic changes, resulting in malnutrition and impaired immune
functions. In this context, parenteral lipid emulsions may modulate inflammatory
and immune reactions, depending on their fatty acid composition. These effects
appear to be based on complex modifications in the composition and structure of
cell membranes, through eicosanoid and cytokine synthesis and by modulation of
gene expression. The pathophysiological mechanisms underlying these fatty acid
induced immune function alterations in critical ill patients are however complex
and partially understood. Indeed, despite a very abundant literature,
experimental and clinical data remain contradictory. The optimization of lipid
emulsion composition thus represents a major challenge for clinical medicine, to
adequately modulate the inflammatory pathways. In the present review, we first
address the metabolic response to aggression, the effects of parenteral lipid
emulsions on inflammation and immunity, and finally the controversial place of
these lipid emulsions during critical illness. The analysis furthermore
highlights the pathophysiological mechanisms underlying the differential effects
of lipid emulsions and their potential for improving the handling of critically
ill patients.
PMID- 26416579
TI - Effect of statin therapy on paraoxonase-1 status: A systematic review and meta
analysis of 25 clinical trials.
AB - BACKGROUND: Decreased activity of the enzyme paraoxonase-1 (PON1) has been
demonstrated in cardiovascular diseases. Statins, the forefront of
pharmacotherapy for dyslipidemia, have been shown to enhance PON1 activity but
clinical findings have not been conclusive. OBJECTIVE: To systematically review
the clinical findings on the impact of statin therapy on PON1 status (protein
concentrations and activities of paraoxonase and arylesterase) and calculate an
effect size for the mentioned effects through meta-analysis of available data.
METHODS: Scopus and Medline databases were searched to identify clinical trials.
A random-effects model and the generic inverse variance method were used for
quantitative data synthesis. Sensitivity analysis was conducted using the one
study remove approach. Random-effects meta-regression was performed to assess the
impact of potential confounders on the estimated effect sizes. RESULTS: Meta
analysis suggested that statin therapy is associated with a significant elevation
of PON1 paraoxonase and arylesterase activities, but not PON1 protein
concentration. The PON1-enhancing effects of statins were robust in the
sensitivity analyses and were independent of statin dose, treatment duration and
changes in plasma low-density lipoprotein cholesterol concentration. CONCLUSION:
The increase of paraoxonase and arylesterase activities with statins is a
pleiotropic lipid-independent clinical benefit that may partly explain the
putative effects of statins in preventing cardiovascular outcomes.
PMID- 26416580
TI - Inhibition of the Rho/Rho kinase pathway prevents lipopolysaccharide-induced
hyperalgesia and the release of TNF-alpha and IL-1beta in the mouse spinal cord.
AB - Administration of lipopolysaccharide (LPS) by various routes produces profound
inflammatory pain hypersensitivity. However, the molecular events that induce
this response remain largely uncharacterized. In the present study, we sought to
elucidate the role of the Rho/Rho kinase (ROCK) pathway in the release of tumor
necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta) following
injection of LPS into the mouse paw, which is associated with nociceptive
behavior. The spinal cord of LPS-treated mice showed increased active GTP-bound
RhoA and upregulation of ROCK2 and c-fos compared to the normal saline group.
Furthermore, the inflammation-related cytokines TNF-alpha and IL-1beta were
markedly increased in the spinal dorsal horn after intraplantar injection of LPS.
However, the latter effects were prevented by prophylactic intrathecal
administration of the Rho inhibitor (C3 exoenzyme) or the ROCK inhibitor
(Y27632). Collectively, our results suggest that the Rho/ROCK signaling pathway
plays a critical role in LPS-induced inflammatory pain and that this pathway is
coincident with the release of the pro-nociceptive cytokines TNF-alpha and IL
1beta, which produces hyperalgesia.
PMID- 26416581
TI - Transcriptomes of parents identify parenting strategies and sexual conflict in a
subsocial beetle.
AB - Parenting in the burying beetle Nicrophorus vespilloides is complex and,
unusually, the sex and number of parents that can be present is flexible. Such
flexibility is expected to involve specialized behaviour by the two sexes under
biparental conditions. Here, we show that offspring fare equally well regardless
of the sex or number of parents present. Comparing transcriptomes, we find a
largely overlapping set of differentially expressed genes in both uniparental and
biparental females and in uniparental males including vitellogenin, associated
with reproduction, and takeout, influencing sex-specific mating and feeding
behaviour. Gene expression in biparental males is similar to that in non-caring
states. Thus, being 'biparental' in N. vespilloides describes the family social
organization rather than the number of directly parenting individuals. There was
no specialization; instead, in biparental families, direct male parental care
appears to be limited with female behaviour unchanged. This should lead to strong
sexual conflict.
PMID- 26416582
TI - Fast probe of local electronic states in nanostructures utilizing a single-lead
quantum dot.
AB - Transport measurements are powerful tools to probe electronic properties of solid
state materials. To access properties of local electronic states in
nanostructures, such as local density of states, electronic distribution and so
on, micro-probes utilizing artificial nanostructures have been invented to
perform measurements in addition to those with conventional macroscopic
electronic reservoirs. Here we demonstrate a new kind of micro-probe: a fast
single-lead quantum dot probe, which utilizes a quantum dot coupled only to the
target structure through a tunneling barrier and fast charge readout by RF
reflectometry. The probe can directly access the local electronic states with
wide bandwidth. The probe can also access more electronic states, not just those
around the Fermi level, and the operations are robust against bias voltages and
temperatures.
PMID- 26416584
TI - An Internet-Based Means of Monitoring Quality of Life in Post-Prostate Radiation
Treatment: A Prospective Cohort Study.
AB - BACKGROUND: Widespread integration of the Internet has resulted in an increase in
the feasibility of using Web-based technologies as a means of communicating with
patients. It may be possible to develop secure and standardized systems that
facilitate Internet-based patient-reported outcomes which could be used to
improve patient care. OBJECTIVE: This study investigates patient interest in
participating in an online post-treatment disease outcomes and quality of life
monitoring program developed specifically for patients who have received
radiation treatment for prostate cancer at a regional oncology center. METHODS:
Patients treated for prostate cancer between 2007 and 2011 (N=1113) at the
British Columbia Cancer Agency, Centre for the Southern Interior were invited by
mail to participate in a standardized questionnaire related to their post
treatment health. Overall participation rates were calculated. In addition,
demographics, access to broadband Internet services, and treatment modalities
were compared between participants and nonparticipants. RESULTS: Of the 1030
eligible invitees, 358 (358/1030, 34.7%) completed the online questionnaire.
Participation rates were higher in individuals younger than age 60 when compared
to those age 60 or older (42% vs 31%) and also for those living in urban areas
compared with rural (37% vs 29%) and in those who received brachytherapy versus
external beam radiotherapy (EBRT) (41% vs 31%). Better participation rates were
seen in individuals who had access to Internet connectivity based on the
different types of broadband services (DSL 35% for those with DSL connectivity vs
29% for those without DSL connectivity; cable 35% vs 32%; wireless 38% vs 26%).
After adjusting for age, the model indicates that lack of access to wireless
broadband connectivity, living in a rural area, and receiving EBRT were
significant predictors of lower participation. CONCLUSIONS: This study
demonstrates that participation rates vary in patient populations within the
interior region of British Columbia, especially with older patients, those in
rural areas, and those with limited access to quality Internet services.
PMID- 26416585
TI - Engineering of high yield production of L-serine in Escherichia coli.
AB - L-serine is a widely used amino acid that has been proposed as a potential
building block biochemical. The high theoretical yield from glucose makes a
fermentation based production attractive. In order to achieve this goal, serine
degradation to pyruvate and glycine in E. coli MG1655 was prevented by deletion
of three L-serine deaminases sdaA, sdaB, and tdcG, as well as serine hydroxyl
methyl transferase (SHMT) encoded by glyA. Upon overexpression of the serine
production pathway, consisting of a feedback resistant version of serA along with
serB and serC, this quadruple deletion strain showed a very high serine
production yield (0.45 g/g glucose) during small-scale batch fermentation in
minimal medium. Serine, however, was found to be highly toxic even at low
concentrations to this strain, which lead to slow growth and production during
fed batch fermentation, resulting in a serine production of 8.3 g/L. The
production strain was therefore evolved by random mutagenesis to achieve
increased tolerance towards serine. Additionally, overexpression of eamA, a
cysteine/homoserine transporter was demonstrated to increase serine tolerance
from 1.6 g/L to 25 g/L. During fed batch fermentation, the resulting strain lead
to the serine production titer of 11.7 g/L with yield of 0.43 g/g glucose, which
is the highest yield reported so far for any organism.
PMID- 26416583
TI - Management of Hematologic Malignancies: Special Considerations in Pregnant Women.
AB - The diagnosis and management of hematologic malignancy during pregnancy is a
significant challenge. This is due to both medical and ethical considerations
regarding when and how to treat this special sub-group of patients. Recurring
uncertainties remain around appropriate imaging techniques, timing and dosage of
chemotherapy, and timing of delivery. In this article we examine and summarize
current literature in this field to assist physicians in their understanding and
management of this patient group. Special attention has been given to diagnostic
and staging procedures, risks associated with chemotherapy at different stages of
gestation, and chemotherapy-dose adaption during pregnancy. In addition,
recommended guidelines for management of lymphoma, leukemia, and planning
delivery are discussed. A multidisciplinary team approach is critical for patient
care, as is shared decision making with the patient and family.
PMID- 26416586
TI - Changes in determinants of compulsory community treatment over 11 years. A
population-based analysis of linked mental health databases.
AB - Differences in patient characteristics, legislation and service setting may
explain variations in the reported efficacy of compulsory treatment orders
(CTOs). Our objective was to investigate factors associated with CTO placement in
Western Australia and see if there were any changes over the 11 years following
their introduction. We used three linked Western Australian databases to compare
2958 patients on community treatment orders with an equal number of controls
matched on age, sex and diagnosis, as well as 2832 consecutive controls selected
on date of discharge from inpatient care or CTO placement. Multivariate analyses
were used to further examine potential predictors of a CTO. The incidence of
CTOs, and the characteristics of patients placed on these orders, showed little
change over 11 years. They tended to be younger and male with schizophrenia or
other non-affective psychotic disorders. Previous health service use as an
inpatient or outpatient also predicted compulsory community treatment.
Psychiatrists in Western Australia appear to be applying community treatment
orders to similar types of patient as elsewhere, but unlike other jurisdictions,
use has not increased. We need further research to establish the relative
contribution of patient characteristics, legislation and service setting toward
the use and outcome of CTOs.
PMID- 26416587
TI - Psychosocial functioning of individuals with schizophrenia in community housing
facilities and the psychiatric hospital in Zurich.
AB - Individuals with severe mental illness frequently have difficulties in obtaining
and maintaining adequate accommodation. If they are not willing or able to adapt
to requirements of traditional supported housing institutions they may live in
sheltered and emergency accommodation. Adequate mental health services are rarely
available in these facilities. The aim of the present study was to evaluate
mental health, functional and social status of individuals living in community
sheltered housing facilities. A cross-sectional survey of n=338 individuals in
sheltered housing compared to a sample of patients at intake in acute inpatient
psychiatry (n=619) concerning clinical and social variables was carried out in
the catchment area of Zurich. Matched subsamples of individuals with
schizophrenia (n=168) were compared concerning functioning and impairments on the
Health of the Nation Outcome Scales (HoNOS). Individuals with schizophrenia in
sheltered housing (25% of the residents) have significantly more problems
concerning substance use, physical illness, psychopathological symptoms other
than psychosis and depression, and relationships, daily activities and occupation
than patients with schizophrenia at intake on an acute psychiatric ward.
Community sheltered accommodation although conceptualized to prevent homelessness
in the general population de facto serve as housing facilities for individuals
with schizophrenia and other severe mental illness.
PMID- 26416588
TI - Associations between five-factor model of the Positive and Negative Syndrome
Scale and plasma levels of monoamine metabolite in patients with schizophrenia.
AB - The five-factor model of the Positive and Negative Syndrome Scale (PANSS) for
schizophrenia symptoms is the most common multiple-factor model used in analyses;
its use may improve evaluation of symptoms in schizophrenia patients. Plasma
monoamine metabolite levels are possible indicators of clinical symptoms or
response to antipsychotics in schizophrenia. We investigated the association
between five-factor model components and plasma monoamine metabolites levels to
explore the model's biological basis. Plasma levels of homovanillic acid (HVA), 3
methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA)
were measured using high-performance liquid chromatography in 65 Japanese
patients with schizophrenia. Significant negative correlation between plasma 5
HIAA levels and the depression/anxiety component was found. Furthermore,
significant positive correlation was found between plasma MHPG levels and the
excitement component. Plasma HVA levels were not correlated with any five-factor
model component. These results suggest that the five-factor model of the PANSS
may have a biological basis, and may be useful for elucidating the
psychopathology of schizophrenia. Assessment using the five-factor model may
enable understanding of monoaminergic dysfunction, possibly allowing more
appropriate medication selection. Further studies of a larger number of first
episode schizophrenia patients are needed to confirm and extend these results.
PMID- 26416589
TI - Perceptual abnormalities related to sensory gating deficit are core symptoms in
adults with ADHD.
AB - This study investigated and compared perceptual abnormalities related to sensory
gating deficit in adult patients with Attention Deficit Disorder with
Hyperactivity (A-ADHD) and adult patients with schizophrenia. Subjects were
evaluated with the Sensory Gating Inventory (SGI). We compared SGI scores between
patients with A-ADHD, patients with schizophrenia and healthy subjects. We also
assessed the relationship between SGI scores and clinical symptoms, and evaluated
the ability of the SGI to detect perceptual abnormalities in A-ADHD. Seventy
adult patients with ADHD reported higher SGI scores than the 70 healthy subjects
and the 70 patients with schizophrenia. The inattention factor of the ASRS
correlated significantly with the overall SGI score. The ROC AUC for the overall
SGI score in the A-ADHD group (versus the healthy group) illustrated good
performance. The findings suggest that i) perceptual abnormalities are core
symptoms of adult patients with ADHD and ii) the attention of patients with A
ADHD may be involuntarily drowned by many irrelevant environmental stimuli
leading to their impaired attention on relevant stimuli. They also confirm that
the SGI could be a useful self-report instrument to diagnose the clinical
features of A-ADHD.
PMID- 26416590
TI - Psychiatric comorbidity in women and men with eating disorders results from a
large clinical database.
AB - Psychiatric comorbidity is common in patients with eating disorders (ED), but
prevalence estimates are heterogeneous, probably due to methodological
differences between studies (population, diagnostic method, sampling procedure
etc.) and a few studies include men. The aim of this study is to investigate
psychiatric DSM-IV Axis I comorbidity in a large sample of adult patients, both
males and females, with the whole spectrum of DSM-IV ED diagnoses. Initial
presentation assessment data on 11,588 adult men and women presenting to
specialist ED clinics in Sweden between 2008 and 2012 were extracted from a large
clinical database. Diagnostics were based on semi-structured interviews (SCID-I)
and the Structured Eating Disorder Interview (SEDI). Seventy-one percent of the
patients with ED had at least one other Axis I disorder. The most common type of
diagnosis was anxiety disorders (53%), where generalized anxiety disorder was the
most common diagnosis. The highest levels of comorbidity were found for women
with Binge Eating Disorder (BED) and men with Bulimia Nervosa (BN). Findings are
consistent with previous research showing a high prevalence of psychiatric
comorbidity in both men and women with ED. The small gender differences observed
seem negligible compared to the general similarity in comorbidity.
PMID- 26416592
TI - Rotifer dynamics in three shallow lakes from the Salado river watershed
(Argentina): the potential modulating role of incident solar radiation.
AB - In turbid Pampean lakes, incident solar radiation is a major driver of plankton
seasonal dynamics. Higher light availability in summer translates into higher
primary production, and therefore more food for zooplankton grazers. However,
experimental evidence suggests that food produced under the high irradiance
conditions prevailing in summer are less suitable to sustain rotifer population
growth than that produced under the lower irradiance conditions typical of
winter. Here, we analysed time series datasets corresponding to three shallow
lakes from the Salado river watershed. This analysis provided evidence for
similar seasonal patterns of rotifer relative abundance over a large geographic
area. In addition, we performed life table experiments to test the hypothesis
that natural seston produced in winter could sustain higher population growth
rates than seston produced in summer. We suggest that the natural seasonal
changes in temperature and food generate successive time windows, which may be
capitalized by the different grazer species, resulting in predictable phenology
of grazer populations.
PMID- 26416591
TI - Family history of alcoholism is related to increased D2 /D3 receptor binding
potential: a marker of resilience or risk?
AB - The aim of this study was to examine the relationship between family history of
alcohol use disorder and striatal dopamine using positron emission tomography
imaging. Participants were 84 healthy, 18- to 30-year-old, social drinkers
recruited via fliers and newspaper advertisements. At assessment, participants
completed measures of lifetime personal and family substance use and psychiatric
symptoms. Participants underwent two consecutive positron emission tomography
scans using the D2 /D3 dopamine receptor radioligand [11 C]raclopride. Scans were
preceded by intravenous saline and amphetamine 0.3 mg/kg, providing measures of
baseline [11 C]raclopride binding potential (BPND ) and change in [11
C]raclopride (DeltaBPND ). Subjective ratings of stimulant drug effects were
collected during scans. Subjects were classified as family history positive (FHP)
if they reported any first-degree relative with alcohol use disorder (AUD) and
family history negative (FHN) if no first-degree relatives had history of AUD.
Participants were predominantly White (69.0 percent) and male (62.1 percent).
Baseline [11 C]raclopride BPND was generally higher in FHP compared with FHN
subjects across striatal subdivisions. There were no differences in DeltaBPND
across regions. Negative subjective drug effects were more pronounced in FHP than
in FHN subjects. While FHN subjects evidenced the expected positive relationship
between DeltaBPND and positive subjective drug effects, this relationship was
disrupted in FHP subjects. There are key differences in dopamine status and
subjective stimulant drug experiences as a function of family AUD history. These
findings have important implications for understanding risk for AUD development
in FHP offspring.
PMID- 26416593
TI - Homeostatic dysregulation proceeds in parallel in multiple physiological systems.
AB - An increasing number of aging researchers believes that multi-system
physiological dysregulation may be a key biological mechanism of aging, but
evidence of this has been sparse. Here, we used biomarker data on nearly 33, 000
individuals from four large datasets to test for the presence of multi-system
dysregulation. We grouped 37 biomarkers into six a priori groupings representing
physiological systems (lipids, immune, oxygen transport, liver function,
vitamins, and electrolytes), then calculated dysregulation scores for each system
in each individual using statistical distance. Correlations among dysregulation
levels across systems were generally weak but significant. Comparison of these
results to dysregulation in arbitrary 'systems' generated by random grouping of
biomarkers showed that a priori knowledge effectively distinguished the true
systems in which dysregulation proceeds most independently. In other words,
correlations among dysregulation levels were higher using arbitrary systems,
indicating that only a priori systems identified distinct dysregulation
processes. Additionally, dysregulation of most systems increased with age and
significantly predicted multiple health outcomes including mortality, frailty,
diabetes, heart disease, and number of chronic diseases. The six systems differed
in how well their dysregulation scores predicted health outcomes and age. These
findings present the first unequivocal demonstration of integrated multi-system
physiological dysregulation during aging, demonstrating that physiological
dysregulation proceeds neither as a single global process nor as a completely
independent process in different systems, but rather as a set of system-specific
processes likely linked through weak feedback effects. These processes--probably
many more than the six measured here--are implicated in aging.
PMID- 26416594
TI - Allopurinol hypersensitivity: investigating the cause and minimizing the risk.
AB - Allopurinol is the most commonly prescribed urate-lowering therapy for the
management of gout. Serious adverse reactions associated with allopurinol, while
rare, are feared owing to the high mortality. Such reactions can manifest as a
rash combined with eosinophilia, leukocytosis, fever, hepatitis and progressive
kidney failure. Risk factors for allopurinol-related severe adverse reactions
include the recent introduction of allopurinol, the presence of the HLA-B(*)58:01
allele, and factors that influence the drug concentration. The interactions
between allopurinol, its metabolite, oxypurinol, and T cells have been studied,
and evidence exists that the presence of the HLA-B(*)58:01 allele and a high
concentration of oxypurinol function synergistically to increase the number of
potentially immunogenic-peptide-oxypurinol-HLA-B(*)58:01 complexes on the cell
surface, thereby increasing the risk of T-cell sensitization and a subsequent
adverse reaction. This Review will discuss the above issues and place this in the
clinical context of reducing the risk of serious adverse reactions.
PMID- 26416595
TI - Rheumatoid arthritis: Autoantibodies, citrullinated histones and initiation of
synovitis.
PMID- 26416596
TI - The inflammasome in fibromyalgia and CRPS: a microglial hypothesis?
PMID- 26416597
TI - Osteoarthritis: Genetically modified ADSCs as cell therapy for OA?
PMID- 26416598
TI - Osteochondrosis, but not lameness, is more frequent among free-range pigs than
confined herd-mates.
AB - BACKGROUND: Organic pig production is expanding and amongst the objectives of
organic farming are enhancing animal health and welfare. However, some studies
have reported a higher prevalence of lameness and joint condemnation at slaughter
in free-range/organic pigs than in conventionally raised pigs. Organic slaughter
pigs have free-range housing in which indoor and outdoor access is compulsory,
while in conventional farming the pigs are commonly confined to indoor pens. The
present study evaluated the effects of free-range and confined housing on
lameness prevalence in a herd of 106 finisher pigs, and whether osteochondrosis
and Erysipelothrix rhusiopathiae associated arthritis influences these effects.
We also evaluated the association between clinical lameness during the rearing
period and joint condemnations at slaughter. RESULTS: Seventy free-range and 36
confined housed fattener pigs were scored for their gait twice during the rearing
period and 848 joints were evaluated post mortem. Osteochondrosis was more
frequent among free-range than confined pigs (P < 0.05), and when present it was
also more severe (P < 0.001). Pigs with more numerous and more severe
osteochondral lesions had their gait affected more than did pigs with fewer such
lesions (P < 0.05). Hence it was a paradox that we did not detect more lameness
among the free-range pigs than the confined pigs. E. rhusiopathiae associated
arthritis was not diagnosed. The association between gait remarks/clinical
lameness and joint condemnations at slaughter was not significant. CONCLUSIONS:
The results indicate that free-range housing may have both positive and negative
effects on locomotory traits. Free-range pigs may be less clinically affected by
osteochondrosis than are confined pigs. One explanation for this effect may be
strengthening of joint supportive tissue and pain relief promoted by exercise.
Visual gait scoring missed serious joint lesions that probably were harmful to
the pigs, and should therefore not be used as a sole indicator of joint/leg
health in welfare inspection of pigs. The association between gait scores and
joint condemnation appeared to be poor. This study was limited to one herd, and
so more and larger studies on the effects of free-range housing on lameness
severity and osteochondrosis development in pigs are recommended.
PMID- 26416599
TI - A CCL21 chemokine of tongue sole (Cynoglossus semilaevis) promotes host
resistance against bacterial infection.
AB - Chemokines are a large family of chemotactic cytokines. Based on the arrangement
of the first two cysteine residues, chemokines are divided into four groups, one
of which is the CC chemokine group. In this study, we characterized a CC
chemokine, CsCCL21, from half-smooth tongue sole (Cynoglossus semilaevis), and
analyzed its activity. CsCCL21 contains two conserved N-terminal cysteine
residues in a NCCL motif and is phylogenetically related to the CCL19/21/25
subgroup of CC chemokines. CsCCL21 was constitutively expressed in nine tissues
and significantly upregulated by bacterial and viral infection. The recombinant
CsCCL21 (rCsCCL21) induced migration of peripheral blood leukocytes. When the two
conserved cysteine residues in the NCCL motif were mutated, the chemotactic
activity of rCsCCL21 was abolished. rCsCCL21 enhanced the resistance of tongue
sole against bacterial infection, but the mutant protein with NCCL mutation
lacked this antibacterial effect. Taken together, these results suggest that
CsCCL21 is a functional CC chemokine with the ability to recruit leukocytes and
is involved in antibacterial immunity in a manner that requires the conserved
NCCL motif.
PMID- 26416601
TI - Diffuse fatty metamorphosis of a large, well-differentiated hepatocellular
carcinoma originating in the normal liver: a case report and literature review.
AB - Fatty changes are frequently observed in small, well-differentiated
hepatocellular carcinomas (HCCs), but are rarely observed in large (over 30 mm in
diameter) lesions. Here, we report a 76-year-old man who developed a large (58 mm
in diameter), well-differentiated HCC with diffuse extensive fatty changes in the
right lobe of the liver. He had no history of alcohol abuse, obesity, or
hepatitis B or C infection, and no autoantibodies, but he did have type 2
diabetes. The serum alpha-fetoprotein level was within the normal range, and
ultrasonography showed a round hyperechoic lesion. Dynamic contrast-enhanced
computed tomography revealed a tumor with inhomogeneous low attenuation in the
arterial, portal, and venous phases, mimicking an angiomyolipoma. The patient
underwent central bisegmentectomy of the liver, and the histological diagnosis
was well-differentiated HCC with diffuse extensive fatty changes. The surrounding
non-cancerous area was normal. A review of the published literature found six
published cases of large, well-differentiated HCC with extensive fatty changes.
Unlike the patients in most previous reports, our patient did not have any
underlying liver disease and had no history of alcohol abuse.
PMID- 26416600
TI - Analysis of the miRNA-mRNA-lncRNA networks in ER+ and ER- breast cancer cell
lines.
AB - Recently, rapid advances in bioinformatics analysis have expanded our
understanding of the transcriptome to a genome-wide level. miRNA-mRNA-lncRNA
interactions have been shown to play critical regulatory role in cancer biology.
In this study, we discussed the use of an integrated systematic approach to
explore new facets of the oestrogen receptor (ER)-regulated transcriptome. The
identification of RNAs that are related to the expression status of the ER may be
useful in clinical therapy and prognosis. We used a network modelling strategy.
First, microarray expression profiling of mRNA, lncRNA and miRNA was performed in
MCF-7 (ER-positive) and MDA-MB-231 cells (ER- negative). A co-expression network
was then built using co-expression relationships of the differentially expressed
mRNAs and lncRNAs. Finally, the selected miRNA-mRNA network was added to the
network. The key miRNA-mRNA-lncRNA interaction can be inferred from the network.
The mRNA and non-coding RNA expression profiles of the cells with different ER
phenotypes were distinct. Among the aberrantly expressed miRNAs, the expression
levels of miR-19a-3p, miR-19b-3p and miR-130a-3p were much lower in the MCF-7
cells, whereas that of miR-148b-3p was much higher. In a cluster of miR-17-92,
the expression levels of six of seven miRNAs were lower in the MCF-7 cells, in
addition to miR-20b in the miR-106a-363 cluster. However, the levels of all the
miRNAs in the miR-106a-25 cluster were higher in the MCF-7 cells. In the co
expression networking, CD74 and FMNL2 gene which is involved in the immune
response and metastasis, respectively, had a stronger correlation with ER. Among
the aberrantly expressed lncRNAs, lncRNA-DLEU1 was highly expressed in the MCF-7
cells. A statistical analysis revealed that there was a co-expression
relationship between ESR1 and lncRNA-DLEU1. In addition, miR-19a and lncRNA-DLEU1
are both located on the human chromosome 13q. We speculate that miR-19a might be
co-expressed with lncRNA-DLEU1 to co-regulate the expression of ESR1, which
influences the occurrence and development of breast cancer cells with different
levels of ER expression. Our findings reveal that the status of ER is mainly due
to the differences in the mRNA and ncRNA profile between the breast cancer cell
lines, and highlight the importance of studying the miRNA-mRNA-lncRNA
interactions to completely illustrate the intricate transcriptome.
PMID- 26416602
TI - Development and Validation of a Multiclass Method for Analysis of Veterinary Drug
Residues in Milk Using Ultrahigh Performance Liquid Chromatography Electrospray
Ionization Quadrupole Orbitrap Mass Spectrometry.
AB - This paper presents the development and validation of a multiclass method for the
analysis of veterinary drug residues in milk using ultrahigh performance liquid
chromatography electrospray ionization quadrupole Orbitrap mass spectrometry
(UHPLC/ESI Q-Orbitrap). The 12 classes of veterinary drugs (a total of 125)
included in this study were endectocides, fluoroquinolones, ionophores,
macrolides, nitroimidazole, NSAIDs, beta-lactams, penicillins, phenicols,
sulfonamides, tetracyclines, and aminoglycosides. Veterinary drug residues in
milk were extracted using a modified salting-out supported liquid extraction
(SOSLE) method, which entailed the precipitation of milk proteins using an
extraction buffer (oxalic acid and EDTA, pH 3) and acetonitrile, a salting-out
acetonitrile/water phase separation using ammonium sulfate, and solid-phase
extraction (SPE) using polymeric reversed-phase sorbent cartridges. The final
extracts were concentrated and reconstituted into a buffer solution and analyzed
using UHPLC/ESI Q-Orbitrap mass spectrometry. The developed method was validated
using a nested experimental design to evaluate the method performance
characteristics, such as overall recovery, intermediate precision, and
measurement uncertainty. The method was able to quantify or screen up to 105
veterinary drugs from 11 different classes, except aminoglycosides. The limits of
quantification were as low as 1.0 MUg/kg, with an analytical range from 1.0 to
100.0 MUg/kg in milk.
PMID- 26416603
TI - Revealing Annexin A2 and ARF-6 enrollment during Trypanosoma cruzi extracellular
amastigote-host cell interaction.
AB - BACKGROUND: Invasion of host cells by Trypanosoma cruzi extracellular amastigotes
is host actin polymerization-dependent. However, the role of proteins related to
actin dynamics during invasion by amastigotes remains to be investigated. Here we
describe the role of Annexin A2 and ARF-6 during extracellular amastigote
mammalian cell interactions. FINDINGS: Our results showed ARF-6 accumulation in
the amastigote-containing parasitophorous vacuole containing amastigote forms;
demonstrated ARF-6 and Annexin A2 critical impact over parasite cell invasion and
revealed the effect of Annexin A2 expression on intracellular parasite
multiplication. CONCLUSION: ARF-6 and Annexin A2 are involved in invasion of
mammalian cells by T. cruzi amastigotes.
PMID- 26416604
TI - Vitamin D metabolism-related genetic variants, dietary protein intake and
improvement of insulin resistance in a 2 year weight-loss trial: POUNDS Lost.
AB - AIMS/HYPOTHESIS: Vitamin D and related genetic variants are associated with
obesity and insulin resistance. We aimed to examine whether vitamin D metabolism
related variants affect changes in body weight and insulin resistance in response
to weight-loss diets varying in macronutrient content. METHODS: Three vitamin D
metabolism-related variants, DHCR7 rs12785878, CYP2R1 rs10741657 and GC
rs2282679, were genotyped in 732 overweight/obese participants from a 2 year
weight-loss trial (POUNDS Lost). We assessed genotype effects on changes in body
weight, fasting levels of glucose and insulin, and HOMA-IR at 6 months (up to 656
participants) and 2 years (up to 596 participants) in response to low-protein vs
high-protein diets, and low-fat vs high-fat diets. RESULTS: We found significant
interactions between DHCR7 rs12785878 and diets varying in protein, but not in
fat, on changes in insulin and HOMA-IR at both 6 months (p for interaction
<0.001) and 2 years (p for interaction <= 0.03). The T allele (vitamin-D
increasing allele) of DHCR7 rs12785878 was associated with greater decreases in
insulin and HOMA-IR (p < 0.002) in response to high-protein diets, while there
was no significant genotype effect on changes in these traits in the low-protein
diet group. Generalised estimating equation analyses indicated significant
genotype effects on trajectory of changes in insulin resistance over the 2 year
intervention in response to high-protein diets (p < 0.001). We did not observe
significant interaction between the other two variants and dietary protein or fat
on changes in these traits. CONCLUSIONS/INTERPRETATION: Our data suggest that
individuals carrying the T allele of DHCR7 rs12785878 might benefit more in
improvement of insulin resistance than noncarriers by consuming high-protein
weight-loss diets. TRIAL REGISTRATION: ClinicalTrials.gov NCT00072995.
PMID- 26416605
TI - Pharmacokinetics of Budesonide Administered with Surfactant in Premature Lambs:
Implications for Neonatal Clinical Trials.
AB - Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature human
infants, which may persist through adulthood. Airway inflammation has been firmly
established in the pathogenesis of BPD. Previous studies to reduce airway
inflammation with high-dose dexamethasone demonstrated adverse neurological
outcomes, despite lower incidences of BPD. Instillation of budesonide and
surfactant can facilitate early extubation and reduce the incidence of BPD and
death among very low birth weight infants. However, the pharmacokinetics of
budesonide and its distribution into the lung and brain are unknown. Therefore, 5
premature lambs were administered 0.25 mg/kg budesonide, with surfactant as the
vehicle. Plasma and tissue samples were taken from the lambs for measurement of
budesonide, 16alpha- hydroxy prednisolone, and budesonide palmitate using
LC/MS/MS. Peak plasma budesonide concentrations were inversely correlated with
the oxygenation index (correlation coefficient of -0.75). plasma budesonide
concentrations were extremely low (~10% of expected) for two lambs that had high
oxygenation indices and were excluded from further analyses. For the remaining 5
premature lambs, a non-compartmental analysis demonstrated an AUCinf of 148.77 +/
28.16 h*MUg/L, half-life of 4.76 +/- 1.79 h, and Cmax of 46.17 +/- 17.71 ug/L.
Using population pharmacokinetic methods, a onecompartment model with exponential
residual error and first-order absorption adequately described the data. The
apparent clearance and apparent volume of distribution of budesonide were
estimated at 6.29 L/h (1.99 L/h/kg) and 29.1 L (9.2 L/kg), respectively.
Budesonide and budesonide palmitate, but not 16alpha-hydroxy prednisolone, were
detected in lung tissue. In this study, budesonide and its metabolites were not
detected in the brain, which suggests that intratracheal instillation suggests
that after local pulmonary deposition, there is no evidence of budesonide
accumulation in the central nervous system. Overall, these results show that peak
plasma budesonide concentrations are inversely correlated with the oxygenation
index and that lung-specific delivery of budesonide avoids accumulation of
budesonide in the brain.
PMID- 26416607
TI - Cytomegalovirus as a potential trigger for systemic lupus erythematosus: a case
report.
AB - BACKGROUND: The role of cytomegalovirus infection in triggering systemic lupus
erythematosus remains a subject of debate. Here, we present a case of childhood
systemic lupus erythematosus with concomitant cytomegalovirus infection, which
sheds light on the relationship between these conditions and their treatment in
pediatric patients. CASE PRESENTATION: A 12-year-old Japanese girl with no
history of systemic illness was diagnosed with systemic lupus erythematosus and
concomitant primary cytomegalovirus infection. Her anti-cytomegalovirus
immunoglobulin G antibodies were elevated during diagnosis and treatment.
Further, the patient's cytomegalovirus pp65 antigenemia level was slightly
elevated (1 cell per 5 * 10(4) cells). Treatment included the administration of
ganciclovir, prednisolone, methylprednisolone, and cyclophosphamide, none of
which prompted adverse effects. The patient was in good condition at the most
recent follow-up. CONCLUSION: Ganciclovir treatment is not completely safe, and
there are no clinical guidelines regarding its use in patients with systemic
lupus erythematosus triggered by cytomegalovirus infection. Our experience with
this case suggests that the decision to administer ganciclovir treatment in
pediatric cases should be guided by a variety of factors in addition to the
cytomegalovirus antigenemia level. These factors include lymphopenia, renal
biopsy results, and cytomegalovirus DNA levels detected by polymerase chain
reaction. The details of our patient's presentation and treatment should prove
illustrative to other clinicians who face similar cases.
PMID- 26416606
TI - Effectiveness of a walking programme to support adults with intellectual
disabilities to increase physical activity: walk well cluster-randomised
controlled trial.
AB - BACKGROUND: Programs to change health behaviours have been identified as one way
to reduce health inequalities experienced by disadvantaged groups. The objective
of this study was to examine the effectiveness of a behaviour change programme to
increase walking and reduce sedentary behaviour of adults with intellectual
disabilities. METHODS: We used a cluster randomised controlled design and
recruited participants over 18 years old and not regularly involved in physical
activity from intellectual disabilities community-based organisations.
Assessments were carried out blind to allocation. Clusters of participants were
randomly allocated to the Walk Well program or a 12-week waiting list control.
Walk Well consisted of three face-to-face physical activity consultations
incorporating behaviour change techniques, written resources for participants and
carers, and an individualised, structured walking programme. The primary outcome
measured with accelerometers was change in mean step count per day between
baseline and 12 weeks. Secondary outcomes included percentage time per day
sedentary and in moderate-vigorous physical activity (MVPA), body mass index
(BMI), and subjective well being. RESULTS: One hundred two participants in 50
clusters were randomised. 82 (80.4%) participants completed the primary outcome.
66.7% of participants lived in the most deprived quintile on the Scottish Index
of Multiple Deprivation. At baseline, participants walked 4780 (standard
deviation 2432) steps per day, spent 65.5% (standard deviation 10.9) of time
sedentary and 59% percent had a body mass in the obesity range. After the walking
programme, the difference between mean counts of the Walk Well and control group
was 69.5 steps per day [95% confidence interval (CI) -1054 to 1193.3]. There were
no significant between group differences in percentage time sedentary 1.6% (95%
CI -2.984 to 6.102), percentage time in MVPA 0.3% (95% CI -0.7 to 1.3), BMI -0.2
kg/m(2) (95% CI -0.8 to 0.4) or subjective well-being 0.3 (95% CI -0.9 to 1.5).
CONCLUSIONS: This is the first published trial of a walking program for adults
with intellectual disabilities. Positively changing physical activity and
sedentary behaviours may require more intensive programmes or upstream approaches
to address the multiple social disadvantages experienced by adults with
intellectual disabilities. Since participants spent the majority of their time
sedentary, home-based programmes to reduce sitting time may be a viable health
improvement approach. TRIAL REGISTRATION: Current Controlled Trials
ISRCTN50494254.
PMID- 26416608
TI - [Formula: see text]Current knowledge on motor disorders in children with autism
spectrum disorder (ASD).
AB - Motor symptomatology in autism is currently poorly understood, and still not
included in the autism spectrum disorder (ASD) diagnostic criteria, although some
studies suggest the presence of motor disturbances in this syndrome. We provide
here a literature review on early motor symptoms in autism, focusing on studies
on psychomotor issues (tone, postural control, manual dexterity, handedness,
praxis). The approach adopted in research to study altered motor behaviors is
generally global and there is no detailed semiology of the motor or neuromotor
disorders observed in people with ASD. This global approach does not enable
understanding of the neuro-developmental mechanisms involved in ASD.
Identification of clinical neuro-psychomotor profiles in reference to a standard
would help to better understand the origin and the nature of the disorders
encountered in ASD, and would thus give new directions for treatment.
PMID- 26416609
TI - In silico evolution of diauxic growth.
AB - BACKGROUND: The glucose effect is a well known phenomenon whereby cells, when
presented with two different nutrients, show a diauxic growth pattern, i.e. an
episode of exponential growth followed by a lag phase of reduced growth followed
by a second phase of exponential growth. Diauxic growth is usually thought of as
a an adaptation to maximise biomass production in an environment offering two or
more carbon sources. While diauxic growth has been studied widely both
experimentally and theoretically, the hypothesis that diauxic growth is a
strategy to increase overall growth has remained an unconfirmed conjecture.
METHODS: Here, we present a minimal mathematical model of a bacterial nutrient
uptake system and metabolism. We subject this model to artificial evolution to
test under which conditions diauxic growth evolves. RESULTS: As a result, we find
that, indeed, sequential uptake of nutrients emerges if there is competition for
nutrients and the metabolism/uptake system is capacity limited. DISCUSSION:
However, we also find that diauxic growth is a secondary effect of this system
and that the speed-up of nutrient uptake is a much larger effect. Notably, this
speed-up of nutrient uptake coincides with an overall reduction of efficiency.
CONCLUSIONS: Our two main conclusions are: (i) Cells competing for the same
nutrients evolve rapid but inefficient growth dynamics. (ii) In the deterministic
models we use here no substantial lag-phase evolves. This suggests that the lag
phase is a consequence of stochastic gene expression.
PMID- 26416610
TI - Vertebral artery injury during foraminal decompression in "low-risk" cervical
spine surgery: incidence and management.
AB - OBJECTIVES: Vertebral artery injury (VAI) during foraminal decompression in
cervical spine surgery in the absence of repositioning or screw stabilization is
rare. Without immediate recognition and treatment, it may have disastrous
consequences. We aimed to describe the incidence and management of iatrogenic VAI
in low-risk cervical spine surgery. MATERIALS AND METHODS: The records of all
patients who underwent surgical procedures of the cervical spine between January
2007 and May 2012 were retrospectively consecutively evaluated. Anterior cervical
discectomy and fusion or arthroplasty as well as dorsal foraminal decompression
through the Frykholm approach in degenerative diseases were defined as low-risk
surgeries (n = 992). RESULTS: VAI occurred in 0.3 % (n = 3) of 992 procedures: in
one case during a dorsal foraminal decompression, and in two cases during the
anterior cervical discectomy and fusion (ACDF) of two or four levels,
respectively. In the first case, the VAI was intraoperatively misdiagnosed.
Despite an initially uneventful course, the patient suffered hemorrhage from a
pseudoaneurysm of the injured VA 1 month after surgery. The aneurysm was
successfully occluded by endovascular coiling. In both ACDF cases, angiography
and endovascular stenting of the lacerated segment proceeded immediately after
the surgery. All three patients suffered no permanent deterioration. CONCLUSIONS:
In a high-volume surgical center, the incidence of VAI during low-risk cervical
spine surgery is extremely low, comprising 0.3 % of all cases. The major risks
are delayed sequels of the vessel wall laceration. In cases of VAI, immediate
angiographic diagnostics and generous indications for endovascular treatment are
obligatory.
PMID- 26416611
TI - Temporal lobe epilepsy and cavernous malformations: surgical strategies and long
term outcomes.
AB - OBJECTIVE: Cerebral cavernous malformations (CCM) of the temporal lobe often
present with seizures. Surgical resection of these lesions can offer durable
seizure control. There is, however, no universally accepted methodology for
assessing and surgically treating these patients. We propose an algorithm to
maximize positive surgical outcomes (seizure control) while minimizing post
surgical neurological deficit. METHODS: A retrospective review of 34 patients who
underwent epilepsy surgery for radiographically proven temporal lobe CCM was
conducted. Patients underwent a relatively standard work-up for seizure
localization. In patients with mesial temporal lobe epilepsy (MTLE), a complete
resection of the epileptogenic zone was performed including amygdalo
hippocampectomy in addition to a lesionectomy if not contraindicated by pre
operative work-up. Patients with neocortical epilepsy underwent intraoperative
electrocorticography (ECoG)-guided lesionectomy. RESULTS: Seizure-free rate for
mesial and neocortical (anterior, lateral, and basal) location was 90 vs. 83 %,
respectively. Complete resection of the lesion, irrespective of location, was
statistically significant for seizure control (p = 0.018). There was no
difference in seizure control based on disease duration or location (p > 0.05).
Patients with mesial temporal CCM who presented with MTLE were presumed to also
have mesial temporal sclerosis (MTS), or dual pathology. These patients underwent
routine resection of the mesial structures. Interestingly, patients who had MTLE
and basal (neocortical) lesions who underwent a mesial resection for suspected
MTS were found not to have dual pathology. CONCLUSIONS: Patients with temporal
lobe CCM should be offered resection for durable seizure control, prevention of
secondary epileptogenic foci, and elimination of hemorrhage risk. The
preoperative work-up should follow a team approach. Surgical intervention should
include complete lesionectomy in all cases. Intra or extra-operative ECoG for
neocortical lesions may be beneficial. Management of mesial temporal CCMs
(archicortex) should consider resection of a well-defined epileptogenic zone
(including mesial structures) due to high probability of pathologically proven
MTS. The use of this treatment algorithm is useful for the education and
treatment of these patients.
PMID- 26416612
TI - Determinants of patient-reported experience of cancer services responsiveness.
AB - BACKGROUND: In coming years, patient-reported data are expected to play a more
prominent role in ensuring early and efficient detection of healthcare system
dysfunctions, developing interventions and evaluating their effects on health
outcomes, and monitoring quality of care from the patient's perspective. The
concept of responsiveness relates to patient-reported experience measures that
focus on the system's response to service users' legitimate expectations. We
explored this concept in an effort to address unresolved issues related to
measuring and interpreting patient experience. Our objectives in this study were
to report on patients' perceptions of cancer services responsiveness and to
identify patient characteristics and organizational attributes that are potential
determinants of a positive patient-reported experience. METHODS: A cross
sectional survey was conducted of 1379 cancer patients in nine participating
ambulatory cancer clinics in hospitals across the province of Quebec, Canada.
They were invited to complete the Cancer Services Responsiveness tool, a 19-item
questionnaire evaluating patients' perceptions of the responsiveness of cancer
services. Sociodemographic data and self-reported clinical and organizational
data were collected. Descriptive statistical analysis, univariate and
multivariate logistic regressions were performed. RESULTS: The patients surveyed
generally perceived cancer services as highly responsive. The individual
determinants of overall responsiveness found to be significant were self-assessed
health status, age, and education level; organizational determinants were
academic affiliation and geographic location of the clinic. DISCUSSION:
Responsiveness refers to distinctive indicators of healthcare quality focused on
patient-provider interactions and presents a complementary picture to other
patient-reported experience measures. The identified determinants of patients'
positive experience with cancer services provide valuable information to guide
care providers in targeting quality improvements. CONCLUSIONS: Finally, our
results suggest these determinants should be further studied to eliminate
confounders and produce usable results.
PMID- 26416613
TI - Current noise as a probe for Wigner molecules.
AB - The effects of a Wigner molecule on the current noise and conductance of a one
dimensional quantum dot with two electrons are investigated. Focusing on a
lateral transport setup, the sequential regime is considered. Tunnelling rates
through the dot are evaluated within an exact diagonalisation scheme. They
strongly depend on electron interactions, showing a markedly different behaviour
in the presence of a Wigner molecule with respect to the weak interactions case,
and thus modify the transport and current noise and the dot. For weak
interactions negative differential conductance and super-Poissonian noise are
found. As interactions increase, a Wigner molecule develops: it suppresses the
negative differential conductance and turns the shot noise to sub-Poissonian
values. In particular, the noise is found to be a sensitive probe of the Wigner
molecule.
PMID- 26416615
TI - Design and synthesis of aromatic molecules for probing electric fields at the
nanoscale.
AB - We propose using halogenated organic dyes as nanoprobes for electric fields and
show their greatly enhanced Stark coefficients using density functional theory
(DFT) calculations. We analyse halogenated variants of three molecules that have
been of interest for cryogenic single molecule spectroscopy: perylene, terrylene,
and dibenzoterrylene, with the zero-phonon optical transitions at blue, red, and
near-infrared. Out of all the combinations of halides and binding sites that are
calculated, we have found that fluorination of the optimum binding site induces a
dipole difference between the ground and excited states larger than 0.5 D for all
three molecules with the highest value of 0.69 D for fluoroperylene. We also
report on the synthesis of 3-fluoroterrylene and the bulk spectroscopy of this
compound in liquid and solid organic environments.
PMID- 26416614
TI - Development and initial evaluation of a semi-automatic approach to assess
perivascular spaces on conventional magnetic resonance images.
AB - PURPOSE: Perivascular spaces (PVS) are associated with ageing, cerebral small
vessel disease, inflammation and increased blood brain barrier permeability. Most
studies to date use visual rating scales to assess PVS, but these are prone to
observer variation. METHODS: We developed a semi-automatic computational method
that extracts PVS on bilateral ovoid basal ganglia (BG) regions on intensity
normalised T2-weighted magnetic resonance images. It uses AnalyzeTM10.0 and was
applied to 100 mild stroke patients' datasets. We used linear regression to test
association between BGPVS count, volume and visual rating scores; and between
BGPVS count & volume, white matter hyperintensity (WMH) rating scores
(periventricular: PVH; deep: DWMH) & volume, atrophy rating scores and brain
volume. RESULTS: In the 100 patients WMH ranged from 0.4 to 119ml, and total
brain tissue volume from 0.65 to 1.45l. BGPVS volume increased with BGPVS count
(67.27, 95%CI [57.93 to 76.60], p<0.001). BGPVS count was positively associated
with WMH visual rating (PVH: 2.20, 95%CI [1.22 to 3.18], p<0.001; DWMH: 1.92,
95%CI [0.99 to 2.85], p<0.001), WMH volume (0.065, 95%CI [0.034 to 0.096],
p<0.001), and whole brain atrophy visual rating (1.01, 95%CI [0.49 to 1.53],
p<0.001). BGPVS count increased as brain volume (as % of ICV) decreased (-0.33,
95%CI [-0.53 to -0.13], p=0.002). COMPARISON WITH EXISTING METHOD: BGPVS count
and volume increased with the overall increase of BGPVS visual scores (2.11,
95%CI [1.36 to 2.86] for count and 0.022, 95%CI [0.012 to 0.031] for volume,
p<0.001). Distributions for PVS count and visual scores were also similar.
CONCLUSIONS: This semi-automatic method is applicable to clinical protocols and
offers quantitative surrogates for PVS load. It shows good agreement with a
visual rating scale and confirmed that BGPVS are associated with WMH and atrophy
measurements.
PMID- 26416616
TI - Lyme Disease Presenting as a Spontaneous Knee Effusion.
AB - Musculoskeletal complaints, which are frequently associated with Lyme disease,
often prompt patients to see a physician. In particular, transient episodes of
spontaneous knee effusion are common early in the progression of Lyme disease,
and, if left untreated, 60% of patients diagnosed with the disease develop Lyme
arthritis. This disease is easily treated with antibiotics; therefore, inclusion
of Lyme disease in the differential diagnosis as a potential cause of a
spontaneous knee effusion can prevent the development of more severe symptoms
associated with the disease. However, the time required to receive test results
and the inconsistencies between serum and synovial tests can complicate diagnosis
of the disease.
PMID- 26416617
TI - Editorial: Calcium in Heart Disease: The Ubiquitous Ion.
PMID- 26416618
TI - Association of left atrial function with incident atypical atrial flutter after
atrial fibrillation ablation.
AB - BACKGROUND: Symptomatic left atrial (LA) flutter (LAFL) is common after atrial
fibrillation (AF) ablation. OBJECTIVE: The purpose of this study was to examine
the association of baseline LA function with incident LAFL after AF ablation.
METHODS: The source cohort included 216 patients with cardiac magnetic resonance
(CMR) before initial AF ablation between 2010 and 2013. Patients who underwent
cryoballoon or laser ablation, patients with AF during CMR, and those with
suboptimal CMR, or missing follow-up data were excluded. Baseline LA volume and
function were assessed by feature-tracking CMR analysis. RESULTS: The final
cohort included 119 patients (mean age 58.9 +/- 11 years; 76.5% men; 70.6%
patients with paroxysmal AF). During a median follow-up of 421 days
(interquartile range 235-751 days), 22 patients (18.5%) had incident LAFL.
Baseline LA volume was similar between the 2 groups. In contrast, baseline
reservoir, conduit, and contractile function of the LA were significantly
impaired in patients with incident LAFL. Baseline global peak longitudinal atrial
strain (PLAS) <22.65% predicted incident LAFL with 86% sensitivity and 68%
specificity (C statistic 0.76). In a multivariable model adjusting for age, heart
failure, and LA volume, PLAS (hazard ratio 0.9 per % increase in PLAS; P = .003)
and LA linear lesions (hazard ratio 2.94; P = .020) were independently associated
with incident LAFL. The coexistence of PLAS <22.65% and linear lesions was
associated with 9-fold increased hazard of incident LAFL. CONCLUSION: Baseline LA
function and linear lesions were independently associated with incident LAFL
after AF ablation. Linear lesions should be limited to selected cases, especially
in patients with impaired LA function.
PMID- 26416620
TI - Flecainide monotherapy is an option for selected patients with catecholaminergic
polymorphic ventricular tachycardia intolerant of beta-blockade.
PMID- 26416619
TI - Mitral valve prolapse and sudden cardiac arrest in the community.
AB - BACKGROUND: Mitral valve prolapse (MVP) is relatively common in the general
population with recently reported prevalence of 1% and familial clustering
(Framingham Heart Study). However, its association with ventricular arrhythmias
and sudden cardiac arrest (SCA) remains controversial. OBJECTIVES: The purpose of
this study was to characterize the frequency and clinical profile of patients
with MVP who suffer SCA in the community. METHODS: Patients with SCA cases were
prospectively identified in the population-based Oregon Sudden Unexpected Death
Study (population ~1 million). The presence of MVP was identified from
echocardiograms recorded prior but unrelated to the SCA event. The detailed
clinical profile of patients with SCA and MVP was compared with that of SCA
patients without MVP to identify potential differences. RESULTS: A total of 729
SCA patients were evaluated over a 12-year period (mean age 69.5 +/- 14.8 years;
64.6% men). MVP was observed in 17 (2.3%) prior to the SCA event (95% confidence
interval 1.2%-3.4%). Mitral regurgitation was present in 14 SCA patients with MVP
(82.3%) and was moderate or severe in 10 (58.8%). Compared with SCA patients
without MVP, SCA patients with MVP were younger (mean age 60.9 +/- 16.4 years vs
69.7 +/- 14.7 years; P = .02), with fewer risk factors (diabetes 5.9% vs 46.4%; P
= .001; hypertension 41.2% vs 78.9%; P = .001) or known coronary disease (29.4%
vs 65.6%; P < .001). CONCLUSION: MVP was observed in a small proportion (2.3%) of
SCA patients in the general population, suggesting a low risk overall. Since SCA
patients with MVP were characterized by younger age and relatively low
cardiovascular comorbidity, a focus on imaging for valve structure/insufficiency
as well as genetics could aid future risk stratification approaches.
PMID- 26416621
TI - Diffuse fibrosis leads to a decrease in unipolar voltage: Validation in a swine
model of premature ventricular contraction-induced cardiomyopathy.
AB - BACKGROUND: Frequent premature ventricular contractions (PVCs) may lead to
dilated cardiomyopathy. A leftward shift in the unipolar voltage distribution in
patients with cardiomyopathy has also been described and attributed to increased
fibrosis. OBJECTIVES: We established a swine model of PVC-induced cardiomyopathy
and assessed (1) whether an increase in left ventricular fibrosis occurs and (2)
whether increased fibrosis leads to a leftward shift in the unipolar voltage
distribution. METHODS: Ten swine underwent implantation of ventricular
pacemakers; 6 programmed to deliver a 50% PVC burden and 4 controls without
pacing. Voltage maps were acquired at baseline and after 14 weeks of ventricular
bigeminy. RESULTS: In the PVC group, left ventricular ejection fraction decreased
from 67% +/- 7% to 44% +/- 15% (P < .05) with no change in controls (71% +/- 6%
to 73% +/- 4%; P = .56). The fifth percentile of the bipolar and unipolar voltage
distribution at baseline was 1.63 and 5.36 mV, respectively. In the control
group, after 14 weeks of pacing there was no significant change in % bipolar
voltage <1.5 mV (pre 1.2% vs post 2.2%; P = .34) or % unipolar voltage <5.5 mV
(pre 4.0% vs post 3.5%; P = .20). In the PVC group, there was a significant
increase in % unipolar voltage <5.5 mV (5.4% vs 12.6%; P < .01), with a leftward
shift in the unipolar voltage distribution. Histologically, % fibrosis was
increased in the PVC group (control 1.8% +/- 1.3% vs PVC 3.4% +/- 2.6%; P < .01).
CONCLUSION: PVC-induced cardiomyopathy in swine leads to an increase in
interstitial fibrosis and a leftward shift in the unipolar voltage distribution.
These findings are consistent with findings in humans with PVC-induced
cardiomyopathy.
PMID- 26416625
TI - Towards defect-free 1-D GaAs/AlGaAs heterostructures based on GaAs nanomembranes.
AB - We demonstrate the growth of defect-free zinc-blende GaAs nanomembranes by
molecular beam epitaxy. Our growth studies indicate a strong impact of As4 re
emission and shadowing in the growth rate of the structures. The highest aspect
ratio structures are obtained for pitches around 0.7-1 MUm and a gallium rate of
1 A s(-1). The functionality of the membranes is further illustrated by the
growth of quantum heterostructures (such as quantum wells) and the
characterization of their optical properties at the nanoscale. This proves the
potential of nanoscale membranes for optoelectronic applications.
PMID- 26416622
TI - Structure and Antioxidant Activities of Proanthocyanidins from Elephant Apple
(Dillenia indica Linn.).
AB - Proanthocyanidins were isolated and purified from fruits of elephant apple
(Dillenia indica Linn.) and their structural and bioactive properties were
examined. Bate-Smith alcoholysis, FTIR, and (13) C NMR spectra revealed that
elephant apple proanthocyanidins (EAPs) contained a dominant amount of B-type
procyanidins (PC) with a minor amount of B-type prodelphinidins (PD) but no A
type interflavan linkage. (13) C NMR spectrum indicated that the cis isomer was
dominant in EAPs. The electron spray ionization and matrix-assisted laser
desorption ionization time of flight mass spectra of EAPs showed the clear ion
peaks corresponding to B-type PC dimer to B-type PD with degree of polymerization
of 11. EAPs had strong antioxidant activity, which was evidenced by the high
oxygen radical scavenging capacity at 1.06 * 10(4) MUmol TE/g and ferric reducing
antioxidant power of 2320 MUmol Fe(II)/g. The results suggest that EAPs could be
extracted to be used as promising functional food materials. PRACTICAL
APPLICATION: In this study, the elephant apple proanthocyanidins (EAPs) with a
yield of 0.23% were identified for the first time as dominant B-type
poly(catechin/epicatechin) but no A-type interflavan linkage. EAPs had higher
ORAC and FRAP values compared to commercial grape seed proanthocyanidins,
suggesting that EAPs may be used as promising functional food materials.
PMID- 26416623
TI - Local bacteria affect the efficacy of chemotherapeutic drugs.
AB - In this study, the potential effects of bacteria on the efficacy of frequently
used chemotherapies was examined. Bacteria and cancer cell lines were examined in
vitro and in vivo for changes in the efficacy of cancer cell killing mediated by
chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was
found to be significantly inhibited by certain bacteria, while the same bacteria
improved the efficacy of six others. HPLC and mass spectrometry analyses of
sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated
modification of drug chemical structure. The chemoresistance or increased
cytotoxicity observed in vitro with sample drugs (gemcitabine and CB1954) was
replicated in in vivo murine subcutaneous tumour models. These findings suggest
that bacterial presence in the body due to systemic or local infection may
influence tumour responses or off-target toxicity during chemotherapy.
PMID- 26416626
TI - Stall no more at polyproline stretches with the translation elongation factors EF
P and IF-5A.
AB - Synthesis of polyproline proteins leads to translation arrest. To overcome this
ribosome stalling effect, bacteria depend on a specialized translation elongation
factor P (EF-P), being orthologous and functionally identical to
eukaryotic/archaeal elongation factor e/aIF-5A (recently renamed 'EF5'). EF-P
binds to the stalled ribosome between the peptidyl-tRNA binding and tRNA-exiting
sites, and stimulates peptidyl-transferase activity, thus allowing translation to
resume. In their active form, both EF-P and e/aIF-5A are post-translationally
modified at a positively charged residue, which protrudes toward the peptidyl
transferase center when bound to the ribosome. While archaeal and eukaryotic IF
5A strictly depend on (deoxy-) hypusination (hypusinylation) of a conserved
lysine, bacteria have evolved diverse analogous modification strategies to
activate EF-P. In Escherichia coli and Salmonella enterica a lysine is extended
by beta-lysinylation and subsequently hydroxylated, whereas in Pseudomonas
aeruginosa and Shewanella oneidensis an arginine in the equivalent position is
rhamnosylated. Inactivation of EF-P, or the corresponding modification systems,
reduces not only bacterial fitness, but also impairs virulence. Here, we review
the function of EF-P and IF-5A and their unusual posttranslational protein
modifications.
PMID- 26416627
TI - Systemic Inflammatory Response Syndrome in End-Stage Heart Failure Patients
Following Continuous-Flow Left Ventricular Assist Device Implantation:
Differences in Plasma Redox Status and Leukocyte Activation.
AB - The role of oxidative stress and leukocyte activation has not been elucidated in
developing systemic inflammatory response syndrome (SIRS) in heart failure (HF)
patients after continuous-flow left ventricular assist device (CF-LVAD)
implantation. The objective of this study was to investigate the change of plasma
redox status and leukocyte activation in CF-LVAD implanted HF patients with or
without SIRS. We recruited 31 CF-LVAD implanted HF patients (16 SIRS and 15 non
SIRS) and 11 healthy volunteers as the control. Pre- and postimplant blood
samples were collected from the HF patients. Plasma levels of oxidized low
density lipoprotein (oxLDL), malondialdehyde (MDA), total antioxidant capacity
(TAC), superoxide dismutase (SOD) in erythrocyte, myeloperoxidase (MPO), and
polymorphonuclear elastase (PMN-elastase) were measured. The HF patients had a
preexisting condition of oxidative stress than healthy controls as evident from
the higher oxLDL and MDA levels as well as depleted SOD and TAC. Leukocyte
activation in terms of higher plasma MPO and PMN-elastase was also prominent in
HF patients than controls. Persistent oxidative stress and reduced antioxidant
status were found to be more belligerent in HF patients with SIRS after the
implantation of CF-LVAD when compared with non-SIRS patients. Similar to
oxidative stress, the activation of blood leukocyte was significantly highlighted
in SIRS patients after implantation compared with non-SIRS. We identified that
the plasma redox status and leukocyte activation became more prominent in CF-LVAD
implanted HF patients who developed SIRS. Our findings suggest that plasma
biomarkers of oxidative stress and leukocyte activation may be associated with
the development of SIRS after CF-LVAD implant surgery.
PMID- 26416631
TI - Huge pseudoaneurysm and cystic adventitial disease from popliteal artery
entrapment.
PMID- 26416628
TI - G protein-coupled estrogen receptor 1 (GPER 1) mediates estrogen-induced,
proliferation of leiomyoma cells.
AB - G protein-coupled estrogen receptor 1 (GPER-1, formerly known as GPR30) has been
proposed as the receptor for estrogen-induced, growth of leiomyomas though its
precise mechanisms of action are not clear. We obtained leiomyoma cells (LC) and
normal smooth muscle cells from 28 women (n = 28, median age 38 years, median
parity 1.0). We incubated them with 17-beta estradiol (E(2)), after blocking, or
upregulating, expression of GPER-1 with ICI182,780 (a GPER-1 agonist) and
siGPR30, respectively. We evaluated the role of GPER-1 in the mitogen-activated
protein kinase (MAPK) signaling pathway using Western blot analysis. We studied
cell proliferation with 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium
bromide, and, mitotic activity with phosphohistone H3 (PPH3) expression in
leiomyoma, and, matched, normal, smooth muscle tissues using standard
immunohistochemistry. Downregulation of GPER-1 expression with siGPR30 partially
attenuated the E(2)-activated MAPK signaling pathway (p < 0.01). Upregulation of
GPER-1 with ICI182,780 enhanced the E(2)-activated MAPK signaling pathway (p <
0.01). ICI182,780 enhanced E(2)-induced proliferation of LC (p < 0.01), while
knock down of the GPER-1 gene with GPER-1 small interfering RNA partially
inhibited E(2)-induced cell proliferation (p < 0.01). There were no significant
differences in PPH3 expression between LCs and normal smooth muscle tissues (p >
0.05). Neither ICI182,780 nor siGPR30 increased mitosis in LCs (p > 0.05). Our
results indicate that GPER-1 mediates proliferation of estrogen-induced, LC by
activating the MAPK pathway, and, not by promoting mitosis.
PMID- 26416632
TI - Aortopulmonary window and interrupted aortic arch with Eisenmenger syndrome in an
adult.
PMID- 26416633
TI - Letter by Guazzi regarding article, "right ventricular function in heart failure
with preserved ejection fraction: a community-based study".
PMID- 26416634
TI - Response to letter regarding article, "right ventricular function in heart
failure with preserved ejection fraction: a community-based study".
PMID- 26416635
TI - Letter by Seropian and Abbate regarding article, "effect of tumor necrosis factor
inhibitor treatment on proximal right coronary chronic total occlusion in a
patient with rheumatoid arthritis".
PMID- 26416636
TI - Response to letter regarding article, "effect of tumor necrosis factor inhibitor
treatment on proximal right coronary chronic total occlusion in a patient with
rheumatoid arthritis".
PMID- 26416637
TI - Letter by Shah and Buch regarding article, "prasugrel plus aspirin beyond 12
months is associated with improved outcomes after TAXUS Liberte paclitaxel
eluting coronary stent placement".
PMID- 26416638
TI - Letter by Jeger and Pfisterer regarding article, "prasugrel plus aspirin beyond
12 months is associated with improved outcomes after TAXUS Liberte paclitaxel
eluting coronary stent placement".
PMID- 26416639
TI - Response to letters regarding article, "prasugrel plus aspirin beyond 12 months
is associated with improved outcomes after TAXUS Liberte paclitaxel-eluting
coronary stent placement".
PMID- 26416640
TI - Correction.
PMID- 26416641
TI - Sphingolipids contribute to acetic acid resistance in Zygosaccharomyces bailii.
AB - Lignocellulosic raw material plays a crucial role in the development of
sustainable processes for the production of fuels and chemicals. Weak acids such
as acetic acid and formic acid are troublesome inhibitors restricting efficient
microbial conversion of the biomass to desired products. To improve our
understanding of weak acid inhibition and to identify engineering strategies to
reduce acetic acid toxicity, the highly acetic-acid-tolerant yeast
Zygosaccharomyces bailii was studied. The impact of acetic acid membrane
permeability on acetic acid tolerance in Z. bailii was investigated with
particular focus on how the previously demonstrated high sphingolipid content in
the plasma membrane influences acetic acid tolerance and membrane permeability.
Through molecular dynamics simulations, we concluded that membranes with a high
content of sphingolipids are thicker and more dense, increasing the free energy
barrier for the permeation of acetic acid through the membrane. Z. bailii
cultured with the drug myriocin, known to decrease cellular sphingo-lipid levels,
exhibited significant growth inhibition in the presence of acetic acid, while
growth in medium without acetic acid was unaffected by the myriocin addition.
Furthermore, following an acetic acid pulse, the intracellular pH decreased more
in myriocin-treated cells than in control cells. This indicates a higher inflow
rate of acetic acid and confirms that the reduction in growth of cells cultured
with myriocin in the medium with acetic acid was due to an increase in membrane
permeability, thereby demonstrating the importance of a high fraction of
sphingolipids in the membrane of Z. bailii to facilitate acetic acid resistance;
a property potentially transferable to desired production organisms suffering
from weak acid stress.
PMID- 26416642
TI - Letter in response to manuscript IJC-D-15-04003 entitled "Comment on
antidepressant use in cardiovascular diseases" by Dr. Onur Durmaz.
PMID- 26416643
TI - Carbon-bridged oligo(p-phenylenevinylene)s for photostable and broadly tunable,
solution-processable thin film organic lasers.
AB - Thin film organic lasers represent a new generation of inexpensive, mechanically
flexible devices for spectroscopy, optical communications and sensing. For this
purpose, it is desired to develop highly efficient, stable, wavelength-tunable
and solution-processable organic laser materials. Here we report that carbon
bridged oligo(p-phenylenevinylene)s serve as optimal materials combining all
these properties simultaneously at the level required for applications by
demonstrating amplified spontaneous emission and distributed feedback laser
devices. A series of six compounds, with the repeating unit from 1 to 6, doped
into polystyrene films undergo amplified spontaneous emission from 385 to 585 nm
with remarkably low threshold and high net gain coefficients, as well as high
photostability. The fabricated lasers show narrow linewidth (<0.13 nm) single
mode emission at very low thresholds (0.7 kW cm(-2)), long operational lifetimes
(>10(5) pump pulses for oligomers with three to six repeating units) and
wavelength tunability across the visible spectrum (408-591 nm).
PMID- 26416644
TI - How can collaboration be strengthened between public health and primary care? A
Dutch multiple case study in seven neighbourhoods.
AB - BACKGROUND: Although public health and primary care share the goal of promoting
the health and wellbeing of the public, the two health sectors find it difficult
to develop mutually integrated plans and to collaborate with each other. The aim
of this multiple case study was to compare seven neighbourhoods in which a
stepwise approach based on two central tools (district health profile and policy
dialogue) was used to develop integrated district plans and promote
collaboration. METHODS: The stepwise approach involved the following steps: 1
Getting to know the neighbourhood, 2 Assembling the workgroup, 3 Analysing the
neighbourhood, 4 Developing a district health profile, 5 Preparing policy
dialogue, 6 Holding local dialogues, 7 Embedding integrated district plans and
collaboration. To supervise this process, a core team was assembled for each
neighbourhood, consisting of people drawn from both public health and primary
care. Both the use of the two tools and the collaboration were studied by means
of documentary analysis, interviews, questionnaires and observations. RESULTS:
The seven neighbourhoods differed in the way the two tools of the stepwise
approach were used: general versus focused profiles, the actors involved, the
aims of the dialogue or the intensity of the steps. There were also similarities:
profile indicators (e.g., population prognosis, vulnerability) and dialogue
themes (e.g., obesity, social cohesion). The local actors experienced that the
combination of both tools facilitates the process of bringing public health and
primary care closer together, and that it is essential to invest sufficiently in
the integration of profile data and in involving appropriate actors in the
dialogue (e.g., GPs, residents). Collaboration was perceived as positive (e.g.,
feels involved, focus on consensus), but a starting process. Local actors also
believe that the stepwise approach supported the process. CONCLUSION: A stepwise
approach involving the combined use of district health profiles and policy
dialogues promotes the integrated planning of health activities and facilitates
collaboration between public health and primary care at the local level. Local
differences may arise in the intensity and form of the various steps, but because
they are practical and clearly defined, they remain transferrable to other
neighbourhoods.
PMID- 26416645
TI - Progression of cervical dilatation.
PMID- 26416647
TI - Pioglitazone--when is a prescription drug safe?
PMID- 26416646
TI - CALHM1 and its polymorphism P86L differentially control Ca2+homeostasis, mitogen
activated protein kinase signaling, and cell vulnerability upon exposure to
amyloid beta.
AB - The mutated form of the Ca2+channel CALHM1 (Ca2+homeostasis modulator 1), P86L
CALHM1, has been correlated with early onset of Alzheimer's disease (AD). P86L
CALHM1 increases production of amyloid beta (Abeta) upon extracellular
Ca2+removal and its subsequent addback. The aim of this study was to investigate
the effect of the overexpression of CALHM1 and P86L-CALHM, upon Abeta treatment,
on the following: (i) the intracellular Ca2+signal pathway; (ii) cell survival
proteins ERK1/2 and Ca2+/cAMP response element binding (CREB); and (iii) cell
vulnerability after treatment with Abeta. Using aequorins to measure the effect
of nuclear Ca2+concentrations ([Ca2+]n ) and cytosolic Ca2+concentrations
([Ca2+]c ) on Ca2+entry conditions, we observed that baseline [Ca2+]n was higher
in CALHM1 and P86L-CALHM1 cells than in control cells. Moreover, exposure to
Abeta affected [Ca2+]c levels in HeLa cells overexpressing CALHM1 and P86L-CALHM1
compared with control cells. Treatment with Abeta elicited a significant decrease
in the cell survival proteins p-ERK and p-CREB, an increase in the activity of
caspases 3 and 7, and more frequent cell death by inducing early apoptosis in
P86L-CALHM1-overexpressing cells than in CALHM1 or control cells. These results
suggest that in the presence of Abeta, P86L-CALHM1 shifts the balance between
neurodegeneration and neuronal survival toward the stimulation of pro-cytotoxic
pathways, thus potentially contributing to its deleterious effects in AD.
PMID- 26416650
TI - Asymmetry in prefrontal resting-state EEG spectral power underlies individual
differences in phasic and sustained cognitive control.
AB - In our daily life, we constantly exert sustained and phasic cognitive control
processes to manage multiple competing task sets and rapidly switch between them.
Increasing research efforts are attempting to unveil how the brain mediates these
processes, highlighting the importance of the prefrontal cortex. An intriguing
question concerns the influence of hemispheric asymmetries and whether it may be
generalized to different cognitive domains depending on lateralized processing.
Another currently open question concerns the underlying causes of the observed
huge inter-individual variability in cognitive control abilities. Here we tackle
these issues by investigating whether participants' hemispheric asymmetry in
intrinsic (i.e., resting-state-related) brain dynamics can reflect differences in
their phasic and/or sustained cognitive control abilities regardless of the
cognitive domain. To this aim, we recorded human participants' resting-state
electroencephalographic activity and performed a source-based spectral analysis
to assess their lateralized brain dynamics at rest. Moreover, we used three task
switching paradigms involving different cognitive domains to assess participants'
domain-general phasic and sustained cognitive control abilities. By performing a
series of correlations and an intersection analysis, we showed that participants
with stronger left- and right-lateralized intrinsic brain activity in the middle
frontal gyrus were more able, respectively, to exert phasic and sustained
cognitive control. We propose that the variability in participants' prefrontal
hemispheric asymmetry in the intrinsic electrophysiological spectral profile
reflects individual differences in preferentially engaging either the left
lateralized, phasic or the right-lateralized, sustained cognitive control
processes to regulate their behavior in response to changing task demands,
regardless of the specific cognitive domain involved.
PMID- 26416648
TI - Vascular autorescaling of fMRI (VasA fMRI) improves sensitivity of population
studies: A pilot study.
AB - The blood oxygenation level-dependent (BOLD) signal is widely used for functional
magnetic resonance imaging (fMRI) of brain function in health and disease. The
statistical power of fMRI group studies is significantly hampered by high inter
subject variance due to differences in baseline vascular physiology. Several
methods have been proposed to account for physiological vascularization
differences between subjects and hence improve the sensitivity in group studies.
However, these methods require the acquisition of additional reference scans
(such as a full resting-state fMRI session or ASL-based calibrated BOLD). We
present a vascular autorescaling (VasA) method, which does not require any
additional reference scans. VasA is based on the observation that slow
oscillations (<0.1Hz) in arterial blood CO2 levels occur naturally due to changes
in respiration patterns. These oscillations yield fMRI signal changes whose
amplitudes reflect the blood oxygenation levels and underlying local
vascularization and vascular responsivity. VasA estimates proxies of the
amplitude of these CO2-driven oscillations directly from the residuals of task
related fMRI data without the need for reference scans. The estimates are used to
scale the amplitude of task-related fMRI responses, to account for vascular
differences. The VasA maps compared well to cerebrovascular reactivity (CVR) maps
and cerebral blood volume maps based on vascular space occupancy (VASO)
measurements in four volunteers, speaking to the physiological vascular basis of
VasA. VasA was validated in a wide variety of tasks in 138 volunteers. VasA
increased t-scores by up to 30% in specific brain areas such as the visual
cortex. The number of activated voxels was increased by up to 200% in brain areas
such as the orbital frontal cortex while still controlling the nominal false
positive rate. VasA fMRI outperformed previously proposed rescaling approaches
based on resting-state fMRI data and can be readily applied to any task-related
fMRI data set, even retrospectively.
PMID- 26416649
TI - Transcranial functional ultrasound imaging of the brain using microbubble
enhanced ultrasensitive Doppler.
AB - Functional ultrasound (fUS) is a novel neuroimaging technique, based on high
sensitivity ultrafast Doppler imaging of cerebral blood volume, capable of
measuring brain activation and connectivity in rodents with high spatiotemporal
resolution (100MUm, 1ms). However, the skull attenuates acoustic waves, so fUS in
rats currently requires craniotomy or a thinned-skull window. Here we propose a
non-invasive approach by enhancing the fUS signal with a contrast agent, inert
gas microbubbles. Plane-wave illumination of the brain at high frame rate (500Hz
compounded sequence with three tilted plane waves, PRF=1500Hz with a 128 element
15MHz linear transducer), yields highly-resolved neurovascular maps. We compared
fUS imaging performance through the intact skull bone (transcranial fUS) versus a
thinned-skull window in the same animal. First, we show that the vascular network
of the adult rat brain can be imaged transcranially only after a bolus
intravenous injection of microbubbles, which leads to a 9dB gain in the contrast
to-tissue ratio. Next, we demonstrate that functional increase in the blood
volume of the primary sensory cortex after targeted electrical-evoked
stimulations of the sciatic nerve is observable transcranially in presence of
contrast agents, with high reproducibility (Pearson's coefficient rho=0.7+/-0.1,
p=0.85). Our work demonstrates that the combination of ultrafast Doppler imaging
and injection of contrast agent allows non-invasive functional brain imaging
through the intact skull bone in rats. These results should ease non-invasive
longitudinal studies in rodents and open a promising perspective for the adoption
of highly resolved fUS approaches for the adult human brain.
PMID- 26416651
TI - V1 surface size predicts GABA concentration in medial occipital cortex.
AB - A number of recent studies have established a link between behavior and the
anatomy of the primary visual cortex (V1). However, one often-raised criticism
has been that these studies provide little insight into the mechanisms of the
observed relationships. As inhibitory neural interactions have been postulated as
an important mechanism for those behaviors related to V1 anatomy, we measured the
concentration of inhibitory gamma-amino butyric acid (GABA) in the medial
occipital cortex where V1 is located using magnetic resonance spectroscopy (MRS)
and estimated the surface area of V1 using fMRI retinotopic mapping. We found a
significant positive relationship between GABA concentration and V1 surface area.
This relationship was present irrespective of whether the MRS voxel had a fixed
size across participants or was proportionally sized to each individual's V1
surface area. Hence, individuals with a larger V1 had a higher GABA concentration
in the medial occipital cortex. By tying together V1 size and GABA concentration,
our findings point towards individual differences in the level of neural
inhibition that might partially mediate the relationships between behavior and V1
neuroanatomy. In addition, they illustrate how stable microscopic properties of
neural activity and function are reflected in macro-measures of V1 structure.
PMID- 26416652
TI - FIACH: A biophysical model for automatic retrospective noise control in fMRI.
AB - Different noise sources in fMRI acquisition can lead to spurious false positives
and reduced sensitivity. We have developed a biophysically-based model (named
FIACH: Functional Image Artefact Correction Heuristic) which extends current
retrospective noise control methods in fMRI. FIACH can be applied to both General
Linear Model (GLM) and resting state functional connectivity MRI (rs-fcMRI)
studies. FIACH is a two-step procedure involving the identification and
correction of non-physiological large amplitude temporal signal changes and
spatial regions of high temporal instability. We have demonstrated its efficacy
in a sample of 42 healthy children while performing language tasks that include
overt speech with known activations. We demonstrate large improvements in
sensitivity when FIACH is compared with current methods of retrospective
correction. FIACH reduces the confounding effects of noise and increases the
study's power by explaining significant variance that is not contained within the
commonly used motion parameters. The method is particularly useful in detecting
activations in inferior temporal regions which have proven problematic for fMRI.
We have shown greater reproducibility and robustness of fMRI responses using
FIACH in the context of task induced motion. In a clinical setting this will
translate to increasing the reliability and sensitivity of fMRI used for the
identification of language lateralisation and eloquent cortex. FIACH can benefit
studies of cognitive development in young children, patient populations and older
adults.
PMID- 26416654
TI - Stability of Crushed Tedizolid Phosphate Tablets for Nasogastric Tube
Administration.
AB - Tedizolid phosphate is approved for the treatment of acute bacterial skin and
skin structure infections. To determine whether the expected dose of tedizolid
phosphate can be delivered via nasogastric tube in patients who have difficulty
swallowing and in whom venous access is not suitable, this in vitro study
evaluated the recovery of tedizolid phosphate 200-mg tablets after crushing,
dispersion in water, and passage through a nasogastric tube. To analyze the
chemical stability of the crushed tablet dispersed in water, the aqueous
preparation was assayed initially after dispersion and again after 4 h at room
temperature. Recovery of tedizolid phosphate after the crushed tablets were
dispersed in water and passed through nasogastric tubes ranged from 92.5 to 97.1
%, which is within the specified acceptance criteria of 90 to 110 %. There was no
significant change in recovery values after 4 h of storage at room temperature
(93.9 % initially and 94.7 % after 4 h). The stability and recovery findings
support the feasibility of administering an aqueous dispersion of crushed
tedizolid phosphate tablets through a nasogastric tube in patients who have
difficulty swallowing and in whom intravenous administration is not possible.
PMID- 26416653
TI - Determinant Factors of the Direct Medical Costs Associated with Genotype 1
Hepatitis C Infection in Treatment-Experienced Patients.
AB - OBJECTIVE: Limited evidence is available on predictors of medical resource
utilization (MRU) and related direct costs, especially in treatment-experienced
patients infected with genotype 1 hepatitis C virus (HCV). This study aimed at
investigating patient and treatment characteristics that predict MRU and related
non-drug costs in treatment-experienced patients with chronic hepatitis C (CHC)
treated with simeprevir (SMV) or telapravir (TVR) in combination with pegylated
interferon and ribavirin (PegIFN/R). PATIENTS AND METHODS: A total of 709
patients who completed the 72-week ATTAIN trial were included in the study. Cost
data were analysed from the UK NHS perspective. Descriptive statistics and
regression analyses were used to determine patterns and predictors of total MRU
related costs associated with SMV/PegIFN/R and TVR/PegIFN/R. RESULTS: Independent
predictors for total MRU-related costs were age, region and the following
interaction terms: (1) gender * F3-F4 METAVIR score * baseline viral load (BLVL),
(2) body mass index (BMI) * F3-F4 METAVIR score * prior response to PegIFN/R and
(3) gender * achievement of SVR at 12 weeks (SVR12) * BLVL. A F3-F4 METAVIR score
was a stronger predictor of total MRU-related costs than SVR12. Predictors of
adverse events included older age, female gender, low BMI, TVR/PegIFN/R and
SVR12. Wilcoxon rank sum test revealed comparable total MRU-related costs between
SMV/PegIFN/R and TVR/PegIFN/R. CONCLUSION: To the best of our knowledge, this
study is the first to describe the relationship between commonly admitted
predictors of MRU-related costs and their joint effect on total MRU-related costs
in treatment-experienced patients with CHC. The identified predictors of MRU
related costs suggest that significant treatment costs can be avoided by starting
treatment early before the disease progresses. Furthermore, adverse events seem
to be the most important factor to take into consideration for the choice of
treatment, especially when therapeutic options are associated with similar levels
of medical resource utilization and associated costs.
PMID- 26416655
TI - Rivaroxaban: An Evaluation of its Cardiovascular Benefit-Risk Profile Across
Indications Based on Numbers Needed to Treat or Harm, and on Clinically
Meaningful Endpoint Comparisons.
AB - The decision to prescribe anticoagulant therapy must consider the balance between
reducing the risk of thromboembolic events and increasing the risk of bleeding.
Although assessments of net clinical outcomes with oral anticoagulants are not
new, this article presents an evaluation of benefit-risk by considering only
events of substantial and comparable clinical relevance (i.e., events with
serious long-term sequelae likely to have irreversible consequences, including
death). This is based on the concept of the number of patients who need to be
treated to elicit one beneficial [number needed to treat (NNT)] or harmful
[number needed to harm (NNH)] event. The approach is illustrated using data from
phase III trials of rivaroxaban, selected because it has the broadest range of
approved indications of the novel oral anticoagulants. For example, in the ATLAS
ACS 2 TIMI 51 trial of rivaroxaban plus standard antiplatelet therapy following
an acute coronary syndrome event, the current analysis demonstrates that 63
patients need to be treated (over 24 months) to prevent one all-cause mortality
event compared with placebo (NNT = 63). Conversely, 500 patients need to be
treated to cause one additional intracranial hemorrhage (NNH = 500). The most
relevant and clinically meaningful assessment of benefit-risk may therefore be
achieved by focusing only on events of greatest concern to patients and
physicians, namely those with (potentially) long-lasting, severe consequences.
Although there are clear limitations to this type of analysis, rivaroxaban
appears to demonstrate a broadly favorable benefit-risk profile across multiple
clinical indications.
PMID- 26416656
TI - Infectious Diseases Society of America and Gain-of-Function Experiments With
Pathogens Having Pandemic Potential.
PMID- 26416657
TI - Gain-of-Function Research and the Relevance to Clinical Practice.
AB - The ongoing moratorium on gain-of-function (GOF) research with highly pathogenic
avian influenza virus, severe acute respiratory syndrome coronavirus, and Middle
East respiratory syndrome coronavirus has drawn attention to the current debate
on these research practices and the potential benefits and risks they present.
While much of the discussion has been steered by members of the microbiology and
policy communities, additional input from medical practitioners will be highly
valuable toward developing a broadly inclusive policy that considers the relative
value and harm of GOF research. This review attempts to serve as a primer on the
topic for the clinical community by providing a historical context for GOF
research, summarizing concerns about its risks, and surveying the medical
products that it has yielded.
PMID- 26416659
TI - Preparation and Characterization of Polymeric Surfactants Based on Epoxidized
Soybean Oil Grafted Hydroxyethyl Cellulose.
AB - Epoxidized soybean oil (ESO) grafted hydroxyethyl cellulose (HEC) was prepared
via ring-opening polymerization, in which the hydroxyl groups of HEC acted as
initiators and the polymeric ESO were covalently bonded to the HEC. Hydrolysis of
ESO-grafted HEC (ESO-HEC) was performed with sodium hydroxide, and the hydrolyzed
ESO-HEC (H-ESO-HEC) products were characterized via Fourier transform infrared
(FT-IR) and (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopies, high
temperature gel permeation chromatography (HT-GPC), and differential scanning
calorimetry (DSC). The results indicated that ring-opening polymerization of ESO
occurred with the hydroxyl groups of HEC as initiators. The molecular weights of
the H-ESO-HEC products were varied by adjusting the mass ratio of HEC and ESO.
Through neutralizing the carboxylic acid of H-ESO-HEC with sodium hydroxide,
novel polymeric surfactants (H-ESO-HEC-Na) were obtained, and the effects of
polymeric surfactants on the surface tension of water were investigated as a
function of concentration of H-ESO-HEC-Na. The H-ESO-HEC-Na was effective at
lowering the surface tension of water to 26.33 mN/m, and the critical micelle
concentration (CMC) value decreased from 1.053 to 0.157 g/L with increases in
molecular weights of the polymeric surfactants. Rheological measurements
indicated that the H-ESO-HEC-Na solutions changed from pseudoplastic property to
Newtonian with increasing shear rate.
PMID- 26416658
TI - Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary
Tuberculosis.
AB - Cavitation in tuberculosis enables highly efficient person-to-person aerosol
transmission. We performed transcriptomics in the rabbit cavitary tuberculosis
model. Among 17 318 transcripts, we identified 22 upregulated proteases. Five
type I collagenases were overrepresented: cathepsin K (CTSK), mast cell chymase-1
(CMA1), matrix metalloproteinase 1 (MMP-1), MMP-13, and MMP-14. Studies of
collagen turnover markers, specifically, collagen type I C-terminal propeptide
(CICP), urinary deoxypyridinoline (DPD), and urinary helical peptide, revealed
that cavitation in tuberculosis leads to both type I collagen destruction and
synthesis and that proteases other than MMP-1, MMP-13, and MMP-14 are involved,
suggesting a key role for CTSK. We confirmed the importance of CTSK upregulation
in human lung specimens, using immunohistochemical analysis, which revealed
perigranulomatous staining for CTSK, and we showed that CTSK levels were
increased in the serum of patients with tuberculosis, compared with those in
controls (3.3 vs 0.3 ng/mL; P = .005).
PMID- 26416660
TI - Femicide and murdered women's children: which future for these children orphans
of a living parent?
AB - BACKGROUND: To assess the prevalence of femicides in Italy over the last three
years and the potential long lasting effects of these traumatic events for the
children of a woman who dies a violent death. METHODS: The data used in this
study come from an internet search for the number of femicides occurring in Italy
between 1(st) January, 2012 and 31(st) October, 2014. RESULTS: The total number
of femicides was 319; the average age of murdered women was 47.50 +/- 19.26. Cold
arms in the form of sharp object -mostly knives- have caused the death of 102/319
women; firearms were used in 87/319 cases; asphyxiation was the chosen method in
52/319 cases. About the place where the femicides occurred, 209/319 were
committed inside the victim's house. Children of women who died a violent death
were 417 with a total of 180 minors in less than three years. A total of 52/417
children were witness to the killing and, among these 30/52 were minors; in
18/417 cases, children were murdered together with their mother and among these
9/18 were minors. CONCLUSIONS: Long-term studies are needed to ascertain what
happens to these children, to understand what are the most appropriate
psychological treatments, the best decisions about the contact with their father
and the best placement for these children.
PMID- 26416661
TI - Elevated microRNA-25 inhibits cell apoptosis in lung cancer by targeting RGS3.
AB - The non-small-cell lung cancer (NSCLC) is the most common type of lung cancer
that affects the human health. But, the underlying mechanisms and effective
therapy are still absent. MicroRNAs (miRNAs) are small RNAs that specifically
bind to the 3' untranslated region (3'UTR) of its target and regulate the protein
level of the target at post-transcriptional level. A lot of miRNAs had been found
abnormally regulated in the NSCLC patients, and understanding their specific
roles in the pathogenesis of NSCLC will help us to develop novel therapeutic
approaches. Here, we reported that miR-25 is dramatically upregulated in NSCLC
tissues and negatively correlated with RGS3 protein. A conserved binding sequence
in the 3'UTR of RGS3 gene to miR-25 was identified, and overexpression of miR-25
induces the RGS3 inhibition. Importantly, suppression of miR-25 facilitates the
cell apoptosis and retards the cell proliferation in A549 and H520 cell lines.
Our data provide a novel miR-25/RGS3 signal in the development of lung cancer.
PMID- 26416662
TI - Affect, Affective Variability, and Physical Health: Results from a Population
Based Investigation in China.
AB - BACKGROUND: There is good evidence linking positive affect with adaptive
psychological and physical health outcomes and negative affect with maladaptive
outcomes, in multiple contexts and samples. However, recent research has
suggested that the fluctuation of emotions, known as affective variability, may
also be an important correlate of individuals' health. PURPOSE: The present study
examined the relationship between affect, affective variability, and self
reported health status in a large representative sample of adults in China.
METHOD: We analyzed cross-sectional data retrieved from the World Health
Organization's study on global ageing and adults' health. A total of 15,050
Chinese adults (aged between 18 and 99) from China reported their affective
experiences during the previous day, perceived health, and their history of
multiple chronic illnesses from their medical records (stroke, angina, diabetes,
chronic lung disease, depression, and hypertension). Hierarchical multiple
regression and logistic regression analyses were employed to analyze the data.
RESULTS: Independent of individuals' mean levels of affect, affective variability
was negatively related to subjective health conditions and positively related to
diagnosed illness status, after controlling for demographic variables. Results
suggest that affective variability increases the likelihood of reported impaired
health and diagnosis of affect-related illnesses such as angina and depression.
CONCLUSION: The present study highlighted the importance of studying the impact
of affective variability, in addition to that of mean affect levels, on health.
PMID- 26416665
TI - Green Propolis: Thirteen Constituents of Polar Extract and Total Flavonoids
Evaluated During Six Years through RP-HPLC.
AB - In order to verify the chemical qualities of polar extract of Green Propolis
produced in the State of Minas Gerais, Brazil, was analyzed by means of RP-HPLC,
the concentration of eleven flavonoids, Artepillin C and p-coumaric acid were
analyzed by means of RP-HPLC. Samples were collected in the months of February,
March, May, July, September, and October, during a period of six years (2008 to
2013) and the results compared with purchased standards. Artepillin C was the
main constituent (80-90%) found in all samples. Lower concentrations of p
coumaric acid, chrysin and kaempferide were observed in March, and of ricin and
galangin in September. Respectively, these months correspond to the end of Summer
and Spring period in Brazil. The variation in concentration of the analyzed
constituents always occurred in the same month, during the entire six years of
evaluation period. All thirteen constituents of Green Propolis were detected
throughout the study period, and the average concentration of each one was
similar in relation to the respective monthly collection period of each year. Due
to similarities among chemical constituents of Green Propolis with those present
in B. dracuncufolia, this plant was identified as being the principal source of
Green Propolis.
PMID- 26416663
TI - Rapid metagenomic identification of viral pathogens in clinical samples by real
time nanopore sequencing analysis.
AB - We report unbiased metagenomic detection of chikungunya virus (CHIKV), Ebola
virus (EBOV), and hepatitis C virus (HCV) from four human blood samples by MinION
nanopore sequencing coupled to a newly developed, web-based pipeline for real
time bioinformatics analysis on a computational server or laptop (MetaPORE). At
titers ranging from 10(7)-10(8) copies per milliliter, reads to EBOV from two
patients with acute hemorrhagic fever and CHIKV from an asymptomatic blood donor
were detected within 4 to 10 min of data acquisition, while lower titer HCV virus
(1 * 10(5) copies per milliliter) was detected within 40 min. Analysis of mapped
nanopore reads alone, despite an average individual error rate of 24 % (range 8
49 %), permitted identification of the correct viral strain in all four isolates,
and 90 % of the genome of CHIKV was recovered with 97-99 % accuracy. Using
nanopore sequencing, metagenomic detection of viral pathogens directly from
clinical samples was performed within an unprecedented <6 hr sample-to-answer
turnaround time, and in a timeframe amenable to actionable clinical and public
health diagnostics.
PMID- 26416666
TI - Branchial cysts: an unusual cause of a mediastinal mass: a case report.
AB - INTRODUCTION: Complex embryological processes form the head and neck of humans.
It is not flawless; remnants lead to sinuses or cysts, commonly in the head and
neck region. CASE PRESENTATION: We present the a case of an 8-year-old boy, a
primary school pupil, from rural Kenya with chronic cough, wheezing, difficulty
in breathing and dyspnea on exertion. He was treated with antibiotics and
antitubercular drugs without improvement prior to referral to our hospital. A
computed tomography scan of his chest revealed a superior mediastinal mass
extending into his neck. A diagnosis of a brachial cleft cyst was made and our
patient underwent a successful excision of the mass through a median strenotomy
and neck dissection. CONCLUSIONS: Branchial cysts of the neck are common,
accounting for 20% of pediatric neck masses. Usually they present as a neck mass
but in our case it presented as a mediastinal mass, which is a very rare clinical
presentation. Surgical excision is the mainstay of treatment. To the surgeon, the
embryology and anatomy should be absolutely clear as dissection may be
challenging due to the close proximity and variable course of the cystic stalk to
major neck vessels and nerves.
PMID- 26416664
TI - Global comparison of chromosome X genes of pulmonary telocytes with mesenchymal
stem cells, fibroblasts, alveolar type II cells, airway epithelial cells, and
lymphocytes.
AB - BACKGROUND: Telocytes (TCs) are suggested as a new type of interstitial cells
with specific telopodes. Our previous study evidenced that TCs differed from
fibroblasts and stem cells at the aspect of gene expression profiles. The present
study aims to search the characters and patterns of chromosome X genes of TC
specific or TC-dominated gene profiles and fingerprints, investigate the network
of principle genes, and explore potential functional association. METHODS: We
compared gene expression profiles in chromosome X of pulmonary TCs with
mesenchymal stem cells (MSC), fibroblasts (Fb), alveolar type II cells (ATII),
airway basal cells (ABC), proximal airway cells (PAC), CD8(+) T cells come from
bronchial lymph nodes (T-BL), or CD8(+) T cells from lungs (T-L) by global
analyses, and selected the genes which were consistently up or down regulated (>1
fold) in TCs compared to other cells as TC-specific genes. The functional and
characteristic networks were identified and compared by bioinformatics tools.
RESULTS: We selected 31 chromosome X genes as the TC-specific or dominated genes,
among which 8 up-regulated (Flna, Msn, Cfp, Col4a5, Mum1l1, Rnf128, Syn1, and
Srpx2) and 23 down-regulated (Abcb7, Atf1, Ddx26b, Drp2, Fam122b, Gyk, Irak1,
Lamp2, Mecp2, Ndufb11, Ogt, Pdha1, Pola1, Rab9, Rbmx2, Rhox9, Thoc2, Vbp1, Dkc1,
Nkrf, Piga, Tmlhe and Tsr2), as compared with other cells. CONCLUSIONS: Our data
suggested that gene expressions of chromosome X in TCs are different with those
in other cells in the lung tissue. According to the selected TC-specific genes,
we infer that pulmonary TCs function as modulators which may enhance cellular
growth and migration, resist senescence, protect cells from external stress,
regulate immune responses, participate in tissue remodeling and repair, regulate
neural function, and promote vessel formation.
PMID- 26416667
TI - Fine-Mapping the Wheat Snn1 Locus Conferring Sensitivity to the Parastagonospora
nodorum Necrotrophic Effector SnTox1 Using an Eight Founder Multiparent Advanced
Generation Inter-Cross Population.
AB - The necrotrophic fungus Parastagonospora nodorum is an important pathogen of one
of the world's most economically important cereal crops, wheat (Triticum aestivum
L.). P. nodorum produces necrotrophic protein effectors that mediate host cell
death, providing nutrients for continuation of the infection process. The recent
discovery of pathogen effectors has revolutionized disease resistance breeding
for necrotrophic diseases in crop species, allowing often complex genetic
resistance mechanisms to be broken down into constituent parts. To date, three
effectors have been identified in P. nodorum. Here we use the effector, SnTox1,
to screen 642 progeny from an eight-parent multiparent advanced generation inter
cross (i.e., MAGIC) population, genotyped with a 90,000-feature single-nucleotide
polymorphism array. The MAGIC founders showed a range of sensitivity to SnTox1,
with transgressive segregation evident in the progeny. SnTox1 sensitivity showed
high heritability, with quantitative trait locus analyses fine-mapping the Snn1
locus to the short arm of chromosome 1B. In addition, a previously undescribed
SnTox1 sensitivity locus was identified on the long arm of chromosome 5A, termed
here QSnn.niab-5A.1. The peak single-nucleotide polymorphism for the Snn1 locus
was converted to the KASP genotyping platform, providing breeders and researchers
a simple and cheap diagnostic marker for allelic state at Snn1.
PMID- 26416670
TI - Finite-size effects and interactions in artificial graphene formed by repulsive
scatterers.
AB - We carry out a numerical real-space study on electrons confined in a two
dimensional triangular lattice of repulsive scattering centres. The system
represents a qualitative model of molecular graphene, where the electron gas is
confined between the scattering molecules in a hexagonal configuration. Our main
interest is, on one hand, in the comparability of a finite system (flake) and a
fully periodic one, and, on the other hand, in the role of the Coulombic electron
electron interactions and the relative strength of the scattering centres. Our
real-space study shows in detail how the density of states of the fully periodic
system-containing the Dirac point-is gradually formed as the size of the flake is
increased. Good qualitative agreement with the experimental density of states is
obtained. Our study confirms the minor role of the electron-electron interactions
with selected system parameters, and shows in detail that large scattering
amplitudes are required to obtain a distinctive Dirac point in the density of
states.
PMID- 26416669
TI - Toppled television sets and head injuries in the pediatric population: a
framework for prevention.
AB - Injuries to children caused by falling televisions have become more frequent
during the last decade. These injuries can be severe and even fatal and are
likely to become even more common in the future as TVs increase in size and
become more affordable. To formulate guidelines for the prevention of these
injuries, the authors systematically reviewed the literature on injuries related
to toppling televisions. The authors searched MEDLINE, PubMed, Embase, Scopus,
CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane
Library, and Google Scholar according to the Cochrane guidelines for all studies
involving children 0-18 years of age who were injured by toppled TVs. Factors
contributing to injury were categorized using Haddon's Matrix, and the public
health approach was used as a framework for developing strategies to prevent
these injuries. The vast majority (84%) of the injuries occurred in homes and
more than three-fourths were unwitnessed by adult caregivers. The TVs were most
commonly large and elevated off the ground. Dressers and other furniture not
designed to support TVs were commonly involved in the TV-toppling incident. The
case fatality rate varies widely, but almost all deaths reported (96%) were due
to brain injuries. Toddlers between the ages of 1 and 3 years most frequently
suffer injuries to the head and neck, and they are most likely to suffer severe
injuries. Many of these injuries require brain imaging and neurosurgical
intervention. Prevention of these injuries will require changes in TV design and
legislation as well as increases in public education and awareness. Television
toppling injuries can be easily prevented; however, the rates of injury do not
reflect a sufficient level of awareness, nor do they reflect an acceptable effort
from an injury prevention perspective.
PMID- 26416668
TI - Genome Sequences of Three Phytopathogenic Species of the Magnaporthaceae Family
of Fungi.
AB - Magnaporthaceae is a family of ascomycetes that includes three fungi of great
economic importance: Magnaporthe oryzae, Gaeumannomyces graminis var. tritici,
and Magnaporthe poae. These three fungi cause widespread disease and loss in
cereal and grass crops, including rice blast disease (M. oryzae), take-all
disease in wheat and other grasses (G. graminis), and summer patch disease in
turf grasses (M. poae). Here, we present the finished genome sequence for M.
oryzae and draft sequences for M. poae and G. graminis var. tritici. We used
multiple technologies to sequence and annotate the genomes of M. oryzae, M. poae,
and G. graminis var. tritici. The M. oryzae genome is now finished to seven
chromosomes whereas M. poae and G. graminis var. tritici are sequenced to 40.0*
and 25.0* coverage respectively. Gene models were developed by the use of
multiple computational techniques and further supported by RNAseq data. In
addition, we performed preliminary analysis of genome architecture and repetitive
element DNA.
PMID- 26416671
TI - Cortical inhibitory deficits in premanifest and early Huntington's disease.
AB - Although progress has been made towards understanding the gross cortical and
subcortical pathology of Huntington's disease (HD), there remains little
understanding of the progressive pathophysiological changes that occur in the
brain circuits underlying the disease. Transcranial magnetic stimulation (TMS)
enables investigation of the functional integrity of cortico-subcortical
pathways, yet it has not been widely applied in HD research to date. This study
sought to characterise profiles of cortical excitability, including inhibition
and facilitation, in groups of premanifest and symptomatic HD participants via
the use of TMS. We also investigated the clinical, neurocognitive and psychiatric
correlates of cortical excitability to better understand the development of
phenotypic heterogeneity. The sample comprised 16 premanifest HD, 12 early
symptomatic HD and 17 healthy control participants. Single- and paired-pulse TMS
protocols were administered to the left primary motor cortex, with surface
electromyography recorded from the abductor pollicis brevis muscle. Short
interval cortical inhibition was significantly reduced in symptomatic HD,
compared with premanifest HD and controls, and was significantly correlated with
pathological burden and neurocognitive performance. There was also reduced long
interval cortical inhibition in both premanifest and symptomatic HD, compared
with controls, which was associated with pathological burden and psychiatric
disturbances. Motor thresholds, cortical silent periods and intracortical
facilitation did not differ across groups. Our results provide important new
insights into pathophysiological changes in cortico-subcortical circuits across
disease stages in HD. We propose that neurophysiological measures obtained via
TMS have potential utility as endophenotypic biomarkers in HD, given their
association with both pathological burden and clinical phenotype.
PMID- 26416672
TI - Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and
behavior.
AB - Neonates that suffer oxygen deprivation during birth can have long lasting
cognitive deficits, such as memory and learning impairments. Hippocampus, one of
the main structures that participate in memory and learning processes, is a
plastic and dynamic structure that conserves during life span the property of
generating new cells which can become neurons, the so-called neurogenesis. The
present study investigated whether a model of rat neonatal anoxia, that causes
only respiratory distress, is able to alter the hippocampal volume, the
neurogenesis rate and has functional implications in adult life. MRI analysis
revealed significant hippocampal volume decrease in adult rats who had
experienced neonatal anoxia compared to control animals for rostral, caudal and
total hippocampus. In addition, these animals also had 55.7% decrease of double
labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate.
Finally, behavioral analysis indicated that neonatal anoxia resulted in
disruption of spatial working memory, similar to human condition, accompanied by
an anxiogenic effect. The observed behavioral alterations caused by oxygen
deprivation at birth might represent an outcome of the decreased hippocampal
neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis.
Therefore, based on current findings we propose this model as suitable to explore
new therapeutic approaches.
PMID- 26416673
TI - Apigenin ameliorates chronic mild stress-induced depressive behavior by
inhibiting interleukin-1beta production and NLRP3 inflammasome activation in the
rat brain.
AB - Increasing evidence suggests that inflammation and oxidative stress may
contribute to the development of major depressive disorder (MDD). Apigenin, a
type of bioflavonoid widely found in citrus fruits, has a number of biological
actions including anti-inflammatory and antioxidant effects. Although apigenin
has potential antidepressant activity, the mechanisms of this effect remain
unclear. The present study aims to investigate the effects of apigenin on
behavioral changes and inflammatory responses induced by chronic unpredictable
mild stress (CUMS) in rats. GW9662, a selective peroxisome proliferator-activated
receptor gamma (PPARgamma) inhibitor, was administered 30 min before apigenin. We
found that treatment with apigenin (20mg/kg, intragastrically) for three weeks
remarkably ameliorated CUMS-induced behavioral abnormalities, such as decreased
locomotor activity and reduced sucrose consumption. In response to oxidative
stress, the NLRP3 inflammasome was activated and IL-1beta secretion increased in
the prefrontal cortex (PFC) of CUMS rats. However, apigenin treatment upregulated
PPARgamma expression and downregulated the expression of NLRP3, which
subsequently downregulated the production of IL-1beta. In addition, GW9662
diminished the inhibitory effects of apigenin on the NLRP3 inflammasome. In
conclusion, our results demonstrate that apigenin exhibits antidepressant-like
effects in CUMS rats, possibly by inhibiting IL-1beta production and NLRP3
inflammasome expression via the up-regulation of PPARgamma expression.
PMID- 26416674
TI - Optical micro-spectroscopy of single metallic nanoparticles: quantitative
extinction and transient resonant four-wave mixing.
AB - We report a wide-field imaging method to rapidly and quantitatively measure the
optical extinction cross-section sigma(ext) (also polarisation resolved) of a
large number of individual gold nanoparticles, for statistically-relevant single
particle analysis. We demonstrate a sensitivity of 5 nm(2) in sigma(ext),
enabling detection of single 5 nm gold nanoparticles with total acquisition times
in the 1 min range. Moreover, we have developed an analytical model of the
polarisation resolved sigma(ext), which enabled us to extract geometrical
particle aspect ratios from the measured sigma(ext). Using this method, we have
characterized a large number of nominally-spherical gold nanoparticles in the 10
100 nm size range. Furthermore, the method provided measurements of in-house
fabricated nanoparticle conjugates, allowing distinction of individual dimers
from single particles and larger aggregates. The same particle conjugates were
investigated correlatively by phase-resolved transient resonant four-wave mixing
micro-spectroscopy. A direct comparison of the phase-resolved response between
single gold nanoparticles and dimers highlighted the promise of the four-wave
mixing technique for sensing applications with dimers as plasmon rulers.
PMID- 26416676
TI - Towards consistent generation of pancreatic lineage progenitors from human
pluripotent stem cells.
AB - Human pluripotent stem cells can in principle be used as a source of any
differentiated cell type for disease modelling, drug screening, toxicology
testing or cell replacement therapy. Type I diabetes is considered a major target
for stem cell applications due to the shortage of primary human beta cells.
Several protocols have been reported for generating pancreatic progenitors by in
vitro differentiation of human pluripotent stem cells. Here we first assessed one
of these protocols on a panel of pluripotent stem cell lines for capacity to
engender glucose sensitive insulin-producing cells after engraftment in
immunocompromised mice. We observed variable outcomes with only one cell line
showing a low level of glucose response. We, therefore, undertook a systematic
comparison of different methods for inducing definitive endoderm and subsequently
pancreatic differentiation. Of several protocols tested, we identified a combined
approach that robustly generated pancreatic progenitors in vitro from both embryo
derived and induced pluripotent stem cells. These findings suggest that, although
there are intrinsic differences in lineage specification propensity between
pluripotent stem cell lines, optimal differentiation procedures may consistently
direct a substantial fraction of cells into pancreatic specification.
PMID- 26416675
TI - Evolution of normal and neoplastic tissue stem cells: progress after Robert
Hooke.
AB - The appearance of stem cells coincides with the transition from single-celled
organisms to metazoans. Stem cells are capable of self-renewal as well as
differentiation. Each tissue is maintained by self-renewing tissue-specific stem
cells. The accumulation of mutations that lead to preleukaemia are in the blood
forming stem cell, while the transition to leukaemia stem cells occurs in the
clone at a progenitor stage. All leukaemia and cancer cells escape being removed
by scavenger macrophages by expressing the 'don't eat me' signal CD47. Blocking
antibodies to CD47 are therapeutics for all cancers, and are currently being
tested in clinical trials in the US and UK.
PMID- 26416677
TI - Somatic cell nuclear transfer: origins, the present position and future
opportunities.
AB - Nuclear transfer that involves the transfer of the nucleus from a donor cell into
an oocyte or early embryo from which the chromosomes have been removed was
considered first as a means of assessing changes during development in the
ability of the nucleus to control development. In mammals, development of embryos
produced by nuclear transfer depends upon coordination of the cell cycles of
donor and recipient cells. Our analysis of nuclear potential was completed in
1996 when a nucleus from an adult ewe mammary gland cell controlled development
to term of Dolly the sheep. The new procedure has been used to target the first
precise genetic modification into livestock; however, the greatest inheritance of
the Dolly experiment was to make biologists think differently. If unknown factors
in the recipient oocyte could reprogramme the nucleus to a stage very early in
development then there must be other ways of making that change. Within 10 years,
two laboratories working independently established protocols by which the
introduction of selected transcription factors changes a small proportion of the
treated cells to pluripotent stem cells. This ability to produce 'induced
pluripotent stem cells' is providing revolutionary new opportunities in research
and cell therapy.
PMID- 26416678
TI - Present and future challenges of induced pluripotent stem cells.
AB - Growing old is our destiny. However, the mature differentiated cells making up
our body can be rejuvenated to an embryo-like fate called pluripotency which is
an ability to differentiate into all cell types by enforced expression of defined
transcription factors. The discovery of this induced pluripotent stem cell (iPSC)
technology has opened up unprecedented opportunities in regenerative medicine,
disease modelling and drug discovery. In this review, we introduce the
applications and future perspectives of human iPSCs and we also show how iPSC
technology has evolved along the way.
PMID- 26416679
TI - Direct somatic lineage conversion.
AB - The predominant view of embryonic development and cell differentiation has been
that rigid and even irreversible epigenetic marks are laid down along the path of
cell specialization ensuring the proper silencing of unrelated lineage
programmes. This model made the prediction that specialized cell types are stable
and cannot be redirected into other lineages. Accordingly, early attempts to
change the identity of somatic cells had little success and was limited to
conversions between closely related cell types. Nuclear transplantation
experiments demonstrated, however, that specialized cells even from adult mammals
can be reprogrammed into a totipotent state. The discovery that a small
combination of transcription factors can reprogramme cells to pluripotency
without the need of oocytes further supported the view that these epigenetic
barriers can be overcome much easier than assumed, but the extent of this
flexibility was still unclear. When we showed that a differentiated mesodermal
cell can be directly converted to a differentiated ectodermal cell without a
pluripotent intermediate, it was suggested that in principle any cell type could
be converted into any other cell type. Indeed, the work of several groups in
recent years has provided many more examples of direct somatic lineage
conversions. Today, the question is not anymore whether a specific cell type can
be generated by direct reprogramming but how it can be induced.
PMID- 26416680
TI - From gristle to chondrocyte transplantation: treatment of cartilage injuries.
AB - This review addresses the progress in cartilage repair technology over the
decades with an emphasis on cartilage regeneration with cell therapy. The most
abundant cartilage is the hyaline cartilage that covers the surface of our joints
and, due to avascularity, this tissue is unable to repair itself. The cartilage
degeneration seen in osteoarthritis causes patient suffering and is a huge burden
to society. The surgical approach to cartilage repair was non-existing until the
1950s when new surgical techniques emerged. The use of cultured cells for cell
therapy started as experimental studies in the 1970s that developed over the
years to a clinical application in 1994 with the introduction of the autologous
chondrocyte transplantation technique (ACT). The technology is now spread
worldwide and has been further refined by combining arthroscopic techniques with
cells cultured on matrix (MACI technology). The non-regenerating hypothesis of
cartilage has been revisited and we are now able to demonstrate cell divisions
and presence of stem-cell niches in the joint. Furthermore, cartilage derived
from human embryonic stem cells and induced pluripotent stem cells could be the
base for new broader cell treatments for cartilage injuries and the future
technology base for prevention and cure of osteoarthritis.
PMID- 26416681
TI - Treatment of Parkinson's disease using cell transplantation.
AB - The clinical trials with intrastriatal transplantation of human fetal
mesencephalic tissue, rich in dopaminergic neurons, in Parkinson's disease (PD)
patients show that cell replacement can work and in some cases induce major, long
lasting improvement. However, owing to poor tissue availability, this approach
can only be applied in very few patients, and standardization is difficult,
leading to wide variation in functional outcome. Stem cells and reprogrammed
cells could potentially be used to produce dopaminergic neurons for
transplantation. Importantly, dopaminergic neurons of the correct substantia
nigra phenotype can now be generated from human embryonic stem cells in large
numbers and standardized preparations, and will soon be ready for application in
patients. Also, human induced pluripotent stem cell-derived dopaminergic neurons
are being considered for clinical translation. Available data justify moving
forward in a responsible way with these dopaminergic neurons, which should be
tested, using optimal patient selection, cell preparation and transplantation
procedures, in controlled clinical studies.
PMID- 26416682
TI - Stem cells for the treatment of heart failure.
AB - Stem cell-based therapy is currently tested in several trials of chronic heart
failure. The main question is to determine how its implementation could be
extended to common clinical practice. To fill this gap, it is critical to first
validate the hypothesis that the grafted stem cells primarily act by harnessing
endogenous repair pathways. The confirmation of this mechanism would have three
major clinically relevant consequences: (i) the use of cardiac-committed cells,
since even though cells primarily act in a paracrine manner, such a phenotype
seems the most functionally effective; (ii) the optimization of early cell
retention, rather than of sustained cell survival, so that the cells reside in
the target tissue long enough to deliver the factors underpinning their action;
and (iii) the reliance on allogeneic cells, the expected rejection of which
should only have to be delayed since a permanent engraftment would no longer be
the objective. One step further, the long-term objective of cell therapy could be
to use the cells exclusively for producing factors and then to only administer
them to the patient. The production process would then be closer to that of a
biological pharmaceutic, thereby facilitating an extended clinical use.
PMID- 26416683
TI - T cell engineering as therapy for cancer and HIV: our synthetic future.
AB - It is now well established that the immune system can control and eliminate
cancer cells. Adoptive T cell transfer has the potential to overcome the
significant limitations associated with vaccine-based strategies in patients who
are often immune compromised. Application of the emerging discipline of synthetic
biology to cancer, which combines elements of genetic engineering and molecular
biology to create new biological structures with enhanced functionalities, is the
subject of this overview. Various chimeric antigen receptor designs,
manufacturing processes and study populations, among other variables, have been
tested and reported in recent clinical trials. Many questions remain in the field
of engineered T cells, but the encouraging response rates pave a wide road for
future investigation into fields as diverse as cancer and chronic infections.
PMID- 26416684
TI - Progressing a human embryonic stem-cell-based regenerative medicine therapy
towards the clinic.
AB - Since the first publication of the derivation of human embryonic stem cells in
1998, there has been hope and expectation that this technology will lead to a
wave of regenerative medicine therapies with the potential to revolutionize our
approach to managing certain diseases. Despite significant resources in this
direction, the path to the clinic for an embryonic stem-cell-based regenerative
medicine therapy has not proven straightforward, though in the past few years
progress has been made. Here, with a focus upon retinal disease, we discuss the
current status of the development of such therapies. We also highlight some of
our own experiences of progressing a retinal pigment epithelium cell replacement
therapy towards the clinic.
PMID- 26416685
TI - Stem cells and the evolving notion of cellular identity.
AB - Stem cells are but one class of the myriad types of cells within an organism.
With potential to self-renew and capacity to differentiate, stem cells play
essential roles at multiple stages of development. In the early embryo,
pluripotent stem cells represent progenitors for all tissues while later in
development, tissue-restricted stem cells give rise to cells with highly
specialized functions. As best understood in the blood, skin and gut, stem cells
are the seeds that sustain tissue homeostasis and regeneration, while in other
tissues like the muscle, liver, kidney and lung, various stem or progenitor cells
play facultative roles in tissue repair and response to injury. Here, I will
provide a brief perspective on the evolving notion of cellular identity and how
reprogramming and transcription factor-mediated conversions of one cell type into
another have fundamentally altered our assumptions about the stability of cell
identity, with profound long-term implications for biomedical research and
regenerative medicine.
PMID- 26416687
TI - Cells: from Robert Hooke to cell therapy--a 350 year journey.
PMID- 26416686
TI - Cell-based therapy technology classifications and translational challenges.
AB - Cell therapies offer the promise of treating and altering the course of diseases
which cannot be addressed adequately by existing pharmaceuticals. Cell therapies
are a diverse group across cell types and therapeutic indications and have been
an active area of research for many years but are now strongly emerging through
translation and towards successful commercial development and patient access. In
this article, we present a description of a classification of cell therapies on
the basis of their underlying technologies rather than the more commonly used
classification by cell type because the regulatory path and manufacturing
solutions are often similar within a technology area due to the nature of the
methods used. We analyse the progress of new cell therapies towards clinical
translation, examine how they are addressing the clinical, regulatory,
manufacturing and reimbursement requirements, describe some of the remaining
challenges and provide perspectives on how the field may progress for the future.
PMID- 26416688
TI - Robotic surgery in children: adopt now, await, or dismiss?
AB - The role of robot-assisted surgery in children remains controversial. This
article aims to distil this debate into an evidence informed decision-making
taxonomy; to adopt this technology (1) now, (2) later, or (3) not at all. Robot
assistance is safe, feasible and effective in selected cases as an adjunctive
tool to enhance capabilities of minimally invasive surgery, as it is known today.
At present, expectations of rigid multi-arm robotic systems to deliver higher
quality care are over-estimated and poorly substantiated by evidence. Such
systems are associated with high costs. Further comparative effectiveness
evidence is needed to define the case-mix for which robot-assistance might be
indicated. It seems unlikely that we should expect compelling patient benefits
when it is only the mode of minimally invasive surgery that differs. Only large
higher-volume institutions that share the robot amongst multiple specialty groups
are likely to be able to sustain higher associated costs with today's technology.
Nevertheless, there is great potential for next-generation surgical robotics to
enable better ways to treat childhood surgical diseases through less invasive
techniques that are not possible today. This will demand customized technology
for selected patient populations or procedures. Several prototype robots
exclusively designed for pediatric use are already under development. Financial
affordability must be a high priority to ensure clinical accessibility.
PMID- 26416689
TI - Forebrain microglia from wild-type but not adult 5xFAD mice prevent amyloid-beta
plaque formation in organotypic hippocampal slice cultures.
AB - The role of microglia in amyloid-beta (Abeta) deposition is controversial. In the
present study, an organotypic hippocampal slice culture (OHSC) system with an in
vivo-like microglial-neuronal environment was used to investigate the potential
contribution of microglia to Abeta plaque formation. We found that microglia
ingested Abeta, thereby preventing plaque formation in OHSCs. Conversely, Abeta
deposits formed rapidly in microglia-free wild-type slices. The capacity to
prevent Abeta plaque formation was absent in forebrain microglia from young adult
but not juvenile 5xFamilial Alzheimer's disease (FAD) mice. Since no loss of
Abeta clearance capacity was observed in both wild-type and cerebellar microglia
from 5xFAD animals, the high Abeta1-42 burden in the forebrain of 5xFAD animals
likely underlies the exhaustion of microglial Abeta clearance capacity. These
data may therefore explain why Abeta plaque formation has never been described in
wild-type mice, and point to a beneficial role of microglia in AD pathology. We
also describe a new method to study Abeta plaque formation in a cell culture
setting.
PMID- 26416690
TI - Strengthening health systems capacity to monitor and evaluate programmes targeted
at reducing abortion-related maternal mortality in Jessore district, Bangladesh.
AB - BACKGROUND: Abortion related deaths as a proportion of maternal mortality appears
to have fallen dramatically in Bangladesh from 5 % in 2001 to 1 % in 2010. Yet
complications from menstrual regulation (MR) and unsafe abortion continue to
cause deleterious health, economic and social consequences for women in the
country. METHODS: This quasi experimental design study with a baseline (January
to December 2008) and an endline survey (August to October 2009) was conducted in
69 public, private, and NGO sector health facilities in Jessore district of
Bangladesh with the objective of adapting and implementing a set of process
indicators, specifically to supplement the indicators for monitoring emergency
obstetric care interventions. At the baseline, we collected retrospective data
from all 69 health facilities that provided MR, legal abortion or post-abortion
care (PAC), by reviewing their last one year's records. Three months after
introducing the safe menstrual regulation and abortion care (SMRAC) model,
endline data was collected. Signal function (critical services that facilities
must perform in order to prevent and treat abortion complications) analysis was
used to characterize facilities as providing basic care, comprehensive care, or
neither. Facility mapping, and records on services provided and complications
treated were used to further characterize service availability and to describe
service use and quality. RESULTS: No facilities fulfilled criteria for
'comprehensive' care at either the baseline or end line while only one met the
'basic' criteria during the endline of the project. Recommended uterine
evacuation technology, manual vacuum aspiration (MVA) was used for 100.0 % of MR
clients but only for 8.0 % or fewer PAC patients. MR clients were 37.5 times more
likely than PAC patients to leave facilities with a contraceptive method (75.0 %
vs. 2.0 %). CONCLUSION: Persistent use of older uterine evacuation technologies
was observed when recommended techniques were widely available in the facilities.
Notable gaps were identified in providing post-abortion contraceptive services
for women treated for PAC. By systematic implementation of the SMRAC model,
health systems can track and measure progress and gaps in their implementation
and identify strategies for further reduction of abortion-related morbidity and
mortality in Bangladesh.
PMID- 26416691
TI - Magnetic colorimetric immunoassay for human interleukin-6 based on the oxidase
activity of ceria spheres.
AB - A novel magnetic colorimetric immunoassay strategy was designed for sensitive
detection of human interleukin-6 (IL-6) using ceria spheres as labels. Ceria
spheres showed excellent oxidase activity, which can directly catalyze the
oxidation of substrate o-phenylenediamine (OPD) to a stable yellow product, 2,3
diaminophenazine (oxOPD). The absorbance of oxOPD was recorded to reflect the
level of IL-6. The relatively mild conditions made the immunoassay strategy more
robust, reliable, and easy. A linear relationship between absorbance intensity
and the logarithm of IL-6 concentrations was obtained in the range of 0.0001-10
ng mL(-1) with a detection limit of 0.04 pg mL(-1) (S/N = 3). The colorimetric
immunoassay exhibited high sensitivity and specificity for the detection of IL-6.
This immunoassay has been successfully applied in the detection of IL-6 in serum
samples and can be readily extended toward the on-site monitoring of cancer
biomarkers in serum samples.
PMID- 26416692
TI - Identification of RNase-resistant RNAs in Saccharomyces cerevisiae extracts:
Separation from chromosomal DNA by selective precipitation.
AB - High-quality chromosomal DNA is a requirement for many biochemical and molecular
biological techniques. To isolate cellular DNA, standard protocols typically lyse
cells and separate nucleic acids from other biological molecules using a
combination of chemical and physical methods. After a standard chemical-based
protocol to isolate chromosomal DNA from Saccharomyces cerevisiae and then
treatment with RNase A to degrade RNA, two RNase-resistant bands persisted when
analyzed using gel electrophoresis. Interestingly, such resistant bands did not
appear in preparations of Escherichia coli bacterial DNA after RNase treatment.
Several enzymatic, chemical, and physical methods were employed in an effort to
remove the resistant RNAs, including use of multiple RNases and alcohol
precipitation, base hydrolysis, and chromatographic methods. These experiments
resulted in the development of a new method for isolation of S. cerevisiae
chromosomal DNA. This method utilizes selective precipitation of DNA in the
presence of a potassium acetate/isopropanol mixture and produces high yields of
chromosomal DNA without detectable contaminating RNAs.
PMID- 26416694
TI - Prevalence and distribution patterns of amphetamine and methamphetamine
consumption in a federal state in southwestern Germany using wastewater analysis.
AB - BACKGROUND: Wastewater analysis is a new approach developed to estimate drug (of
abuse) consumption in large communities, such as cities or even whole countries.
AIMS: This paper presents data on the loads of amphetamine and methamphetamine
measured in ten wastewater treatment plants in different parts of a German
federal state. It provides an estimation of the intensity of the consumption and
a comparison to other regions in Germany and Europe. METHODS: Consumption of
amphetamine and methamphetamine was estimated by analysis of drug residues in
composite 24h samples of wastewater after mechanical treatment over one week by
liquid chromatography-high resolution tandem mass spectrometry. Samples were
collected from the inlet of ten wastewater treatment plants (WWTP) in the federal
state of Saarland, representing bigger cities (>200,000 inhabitants), medium
sized cities (>50,000 inhabitants), small cities (>25,000 inhabitants), and
villages (<25,000 inhabitants). In each WWTP, samples were taken daily for seven
consecutive days in July 2014. RESULTS: We observed differences of amphetamine
versus methamphetamine loads (expressed as mg/day/1000 inhabitants): Amphetamine
loads were much higher in all tested WWTPs indicating a low prevalence of
methamphetamine abuse in the federal state of Saarland at the tested period.
These findings are in line with previous reports about the distribution of
amphetamine and methamphetamine in Germany and Europe. CONCLUSIONS: The approach
confirms that wastewater analysis can provide valuable data about the abuse
pattern of drugs of abuse in cities and larger areas. It can be useful for
planning interventions aimed at specific areas and substances.
PMID- 26416695
TI - Alterations of neuronal precursor cells in stages of human adult neurogenesis in
heroin addicts.
AB - BACKGROUND: Adult neurogenesis has been shown to occur throughout life and
different brain pathologies were demonstrated to be associated with altered
neurogenesis. Here, an impact of heroin addiction on neurogenesis in humans is
hypothesised. METHODS: Post mortem hippocampal specimens of drug addicts with
known heroin abuse and a group of non-addictive control subjects were analysed,
using antibodies indicating different stages of neurogenesis. The subgranular
zone of the dentate gyrus was examined qualitatively and quantitatively. RESULTS:
The data indicate (i) a decreased number of neural precursor cells, (ii)
accompanied by low rates of proliferation and (iii) a marked loss of dendritic
trees in targeting cells in heroin fatalities. (iv) The age-dependent increase of
differentiating cells in the healthy controls was not observed in the addicts.
Additionally, double immunofluorescence labelling indicated the precursor nature
of Musashi-1 positive cells in the human subgranular zone of the dentate gyrus.
CONCLUSIONS: Present data firstly demonstrate the influence of drug addiction
with known heroin abuse on different developmental stages of progenitors in the
dentate gyrus. The patterns of antibody staining suggest a distinct inhibition of
neurogenesis at the stage of neural precursor cells and revealed morphological
changes in targeting cells in cases of heroin addicts as compared to healthy
controls. These alterations could be considerable for memory and cognitive
deficits as well as addictive behaviour in chronic drug abusers and may give rise
to specific pro-neurogenic therapies.
PMID- 26416693
TI - Next generation sequencing profiling identifies miR-574-3p and miR-660-5p as
potential novel prognostic markers for breast cancer.
AB - BACKGROUND: Prognostication of Breast Cancer (BC) relies largely on traditional
clinical factors and biomarkers such as hormone or growth factor receptors. Due
to their suboptimal specificities, it is challenging to accurately identify the
subset of patients who are likely to undergo recurrence and there remains a major
need for markers of higher utility to guide therapeutic decisions. MicroRNAs
(miRNAs) are small non-coding RNAs that function as post-transcriptional
regulators of gene expression and have shown promise as potential prognostic
markers in several cancer types including BC. RESULTS: In our study, we sequenced
miRNAs from 104 BC samples and 11 apparently healthy normal (reduction
mammoplasty) breast tissues. We used Case-control (CC) and Case-only (CO)
statistical paradigm to identify prognostic markers. Cox-proportional hazards
regression model was employed and risk score analysis was performed to identify
miRNA signature independent of potential confounders. Representative miRNAs were
validated using qRT-PCR. Gene targets for prognostic miRNAs were identified using
in silico predictions and in-house BC transcriptome dataset. Gene ontology terms
were identified using DAVID bioinformatics v6.7. A total of 1,423 miRNAs were
captured. In the CC approach, 126 miRNAs were retained with predetermined
criteria for good read counts, from which 80 miRNAs were differentially
expressed. Of these, four and two miRNAs were significant for Overall Survival
(OS) and Recurrence Free Survival (RFS), respectively. In the CO approach, from
147 miRNAs retained after filtering, 11 and 4 miRNAs were significant for OS and
RFS, respectively. In both the approaches, the risk scores were significant after
adjusting for potential confounders. The miRNAs associated with OS identified in
our cohort were validated using an external dataset from The Cancer Genome Atlas
(TCGA) project. Targets for the identified miRNAs were enriched for cell
proliferation, invasion and migration. CONCLUSIONS: The study identified twelve
non-redundant miRNAs associated with OS and/or RFS. These signatures include
those that were reported by others in BC or other cancers. Importantly we report
for the first time two new candidate miRNAs (miR-574-3p and miR-660-5p) as
promising prognostic markers. Independent validation of signatures (for OS) using
an external dataset from TCGA further strengthened the study findings.
PMID- 26416696
TI - Sample size calculation for before-after experiments with partially overlapping
cohorts.
AB - We investigate sample size calculation for before-after experiments where the
outcome of interest is binary and the enrolled subjects contribute a mixed type
of data: some subjects contribute complete pairs of before- and after
intervention outcomes, while some subjects contribute incomplete data (before
intervention only or after-intervention only). We use the GEE approach to derive
a closed-form sample size formula by treating the incomplete observations as
missing data in a generalized linear model. The impacts of various designing
factors are appropriately accounted for in the sample size formula, including
intervention effect, baseline response rate, within-subject correlation, and
distribution of missing values in the before- and after-intervention periods. We
illustrate sample size estimation using a real application example. We conduct
simulation studies to demonstrate that the proposed sample size maintains the
nominal power and type I error under a wide spectrum of trial configurations.
PMID- 26416697
TI - Predictors and Outcomes of Burnout in Primary Care Physicians.
AB - OBJECTIVE: To assess relationships between primary care work conditions,
physician burnout, quality of care, and medical errors. METHODS: Cross-sectional
and longitudinal analyses of data from the MEMO (Minimizing Error, Maximizing
Outcome) Study. Two surveys of 422 family physicians and general internists,
administered 1 year apart, queried physician job satisfaction, stress and
burnout, organizational culture, and intent to leave within 2 years. A chart
audit of 1795 of their adult patients with diabetes and/or hypertension assessed
care quality and medical errors. KEY RESULTS: Women physicians were almost twice
as likely as men to report burnout (36% vs 19%, P < .001). Burned out clinicians
reported less satisfaction (P < .001), more job stress (P < .001), more time
pressure during visits (P < .01), more chaotic work conditions (P < .001), and
less work control (P < .001). Their workplaces were less likely to emphasize work
life balance (P < .001) and they noted more intent to leave the practice (56% vs
21%, P < .001). There were no consistent relationships between burnout, care
quality, and medical errors. CONCLUSIONS: Burnout is highly associated with
adverse work conditions and a greater intention to leave the practice, but not
with adverse patient outcomes. Care quality thus appears to be preserved at great
personal cost to primary care physicians. Efforts focused on workplace redesign
and physician self-care are warranted to sustain the primary care workforce.
PMID- 26416698
TI - Application of Sensory Evaluation, HS-SPME GC-MS, E-Nose, and E-Tongue for
Quality Detection in Citrus Fruits.
AB - In this study, electronic tongue (E-tongue), headspace solid-phase
microextraction gas chromatography-mass spectrometer (GC-MS), electronic nose (E
nose), and quantitative describe analysis (QDA) were applied to describe the 2
types of citrus fruits (Satsuma mandarins [Citrus unshiu Marc.] and sweet oranges
[Citrus sinensis {L.} Osbeck]) and their mixing juices systematically and
comprehensively. As some aroma components or some flavor molecules interacted
with the whole juice matrix, the changes of most components in the fruit juice
were not in proportion to the mixing ratio of the 2 citrus fruits. The potential
correlations among the signals of E-tongue and E-nose, volatile components, and
sensory attributes were analyzed by using analysis of variance partial least
squares regression. The result showed that the variables from the sensor signals
(E-tongue system and E-nose system) had significant and positive (or negative)
correlations to the most variables of volatile components (GC-MS) and sensory
attributes (QDA). The simultaneous utilization of E-tongue and E-nose obtained a
perfect classification result with 100% accuracy rate based on linear
discriminant analysis and also attained a satisfying prediction with high
coefficient association for the sensory attributes (R(2) > 0.994 for training
sets and R(2) > 0.983 for testing sets) and for the volatile components (R(2) >
0.992 for training sets and R(2) > 0.990 for testing sets) based on random
forest. Being easy-to-use, cost-effective, robust, and capable of providing a
fast analysis procedure, E-nose and E-tongue could be used as an alternative
detection system to traditional analysis methods, such as GC-MS and sensory
evaluation by human panel in the fruit industry. PRACTICAL APPLICATION: Being
easy-to-use, cost-effective, robust, and capable of providing a fast analysis
procedure, E-nose and E-tongue could be used as an alternative detection system
to traditional analysis methods for characterizing food flavors. Based on those
results, one can draw a conclusion that the fusion system composed of E-tongue
and E-nose could guarantee a satisfying result in the prediction of sensory
attributes and volatile components for fruit quality profile.
PMID- 26416699
TI - Investigating the effect of structural transition on aggregation of beta
lactoglobulin.
AB - beta-lactoglobulin (BLG), the major bovine whey protein, is a well-characterized
globular protein. It is a model protein for studying the structural transition
and aggregation. BLG unfolds and aggregates through chemical and physical
processes. It is a predominantly beta-sheet protein but, the non-native alpha
helical intermediate accumulates in its folding pathway. The present study aims
to understand more about which stage of the protein folding is prone to
aggregation. The intermediate states were trapped by TFE and their aggregation
and structural changes evaluated, for this purpose. The experiments were carried
out at various pH values, ionic strengths, protein concentrations and heating
times by turbidity measurements, circular dichroism and fluorescence
spectroscopy. Furthermore, the aggregated species at various molecular weights
were detected by SDS-PAGE. Only a small change was observed in the secondary and
tertiary structures of the protein at 10% TFE, but a further increase of TFE
concentration results in induction of new alpha-helical structure and disruption
of the rigid tertiary structure. The turbidity measurement indicated that the
aggregation of BLG reaches a maximum level at 10% TFE on all experimental
conditions and from this point forward, it decreases with increasing the amount
of TFE. In conclusion, the results showed that the alpha-helical state is
resistant to aggregation, in spite that its tertiary structure is partially
unfolded. BLG becomes prone to aggregation, when its non-native alpha-helical
structure converts to the beta-sheet structure.
PMID- 26416701
TI - Facile synthesis of hydrangea flower-like hierarchical gold nanostructures with
tunable surface topographies for single-particle surface-enhanced Raman
scattering.
AB - The physicochemical properties of noble metal nanocrystals depend strongly on
their size and shape, and it is becoming clear that the design and facile
synthesis of particular nanostructures with tailored shape and size is especially
important. Herein a novel class of hydrangea flower-like hierarchical gold
nanostructures with tunable surface topographies and optical properties are
prepared for the first time by a facile, one-pot, seedless synthesis using
ascorbic acid (AA) to reduce hydrogen tetrachloroaurate (HAuCl4) in the presence
of (1-hexadecyl)trimethylammonium chloride (CTAC). The morphologies of the
synthesized gold nanoflowers are controlled and fine-tuned by varying the
synthetic conditions such as the concentration of reagents and the growth
temperature. Due to their unique hierarchical three-dimensional (3D) structures
with rich hot spots, these gold nanoflowers exhibit an efficient performance in
single-particle surface-enhanced Raman scattering (SERS). The work stands out as
an interesting approach for anisotropic particle synthesis and morphological
control, and the proposed novel, hierarchical gold nanoflowers have a number of
exciting potential applications in SERS-based sensors.
PMID- 26416702
TI - Affect-regulated exercise: an alternative approach for lifestyle modification in
overweight/obese women with polycystic ovary syndrome.
AB - OBJECTIVE: Affect-regulated exercise ("ARE") is an alternative approach to guide
exercise intensity based on feeling of pleasure. The aim of this study was to
analyze if overweight/obese women with polycystic ovary syndrome (PCOS) meet the
American College of Sports Medicine (ACSM) recommendation regarding to exercise
intensity to improve health status during a single bout of "ARE". METHODS: A
sample of 14 overweight/obese women with PCOS (18-34 years) performed a single
bout of "ARE" (40 min of aerobic exercise on outdoor track). The Feeling Scale
(FS) was used to guide "ARE" intensity/pace maintaining an affective valence
between "good" and "very good" during all time. Heart rate (HR), speed, % of HR
at first and second ventilatory threshold (VT1 and VT2) and time spent at
moderate (64-76% of HR(max)) and vigorous (77-95% of HR(max)) intensity during
"ARE" were measured with a global positioning system (GPS) device. RESULTS:
Volunteers exercised at 73% (68-78%) of HR(max), 5.8 (5.2-6.2) km/h, 93.4% of HR
at VT1 (89.3-98.2) and 80.5% of HR at VT2 (75.3-84.6) and spent >80% of time at
moderate intensity. CONCLUSIONS: Overweight/obese women with PCOS met the ACSM
recommendation regarding exercise intensity to improve health status when
exercised between "good" and "very good" of FS. Thus, "ARE" may be an interesting
approach to be used in clinical practice regarding to exercise prescription
and/or physical activity advice.
PMID- 26416704
TI - Liver transplantation for secondary liver tumours.
PMID- 26416703
TI - CBX7 and miR-9 are part of an autoregulatory loop controlling p16(INK) (4a).
AB - Polycomb repressive complexes (PRC1 and PRC2) are epigenetic regulators that act
in coordination to influence multiple cellular processes including pluripotency,
differentiation, cancer and senescence. The role of PRCs in senescence can be
mostly explained by their ability to repress the INK4/ARF locus. CBX7 is one of
five mammalian orthologues of Drosophila Polycomb that forms part of PRC1.
Despite the relevance of CBX7 for regulating senescence and pluripotency, we have
a limited understanding of how the expression of CBX7 is regulated. Here we
report that the miR-9 family of microRNAs (miRNAS) downregulates the expression
of CBX7. In turn, CBX7 represses miR-9-1 and miR-9-2 as part of a regulatory
negative feedback loop. The miR-9/CBX7 feedback loop is a regulatory module
contributing to induction of the cyclin-dependent kinase inhibitor (CDKI)
p16(INK4a) during senescence. The ability of the miR-9 family to regulate
senescence could have implications for understanding the role of miR-9 in cancer
and aging.
PMID- 26416705
TI - Exciton dynamics of C60-based single-photon emitters explored by Hanbury Brown
Twiss scanning tunnelling microscopy.
AB - Exciton creation and annihilation by charges are crucial processes for
technologies relying on charge-exciton-photon conversion. Improvement of organic
light sources or dye-sensitized solar cells requires methods to address exciton
dynamics at the molecular scale. Near-field techniques have been instrumental for
this purpose; however, characterizing exciton recombination with molecular
resolution remained a challenge. Here, we study exciton dynamics by using
scanning tunnelling microscopy to inject current with sub-molecular precision and
Hanbury Brown-Twiss interferometry to measure photon correlations in the far
field electroluminescence. Controlled injection allows us to generate excitons in
solid C60 and let them interact with charges during their lifetime. We
demonstrate electrically driven single-photon emission from localized structural
defects and determine exciton lifetimes in the picosecond range. Monitoring
lifetime shortening and luminescence saturation for increasing carrier injection
rates provides access to charge-exciton annihilation dynamics. Our approach
introduces a unique way to study single quasi-particle dynamics on the ultimate
molecular scale.
PMID- 26416706
TI - An augmented supermatrix phylogeny of the avian family Picidae reveals
uncertainty deep in the family tree.
AB - The accumulation of DNA sequence data in public repositories allows for
phylogenetic inference on unprecedented taxonomic scales using supermatrix
approaches. Careful analysis of available data allows strategic augmentation with
new sequences in order to maximize taxonomic sampling and coverage of informative
loci. I inferred relationships among 179 species (76%) in the avian family
Picidae (woodpeckers, piculets, and wrynecks), using publicly available sequence
data supplemented with targeted sequencing to increase species-level and locus
level sampling and maximize resolution. Results of these analyses generally
corroborate previous molecular studies, with consensus on the membership of most
genera and tribes. However, several newly placed taxa show surprising affinities,
and several genera as currently delineated appear to be paraphyletic.
Relationships among major clades of Picidae remain poorly resolved, particularly
among the three lineages of piculets, the unusual woodpecker genus Hemicircus,
and the remaining woodpeckers, and among the major groups of true woodpeckers
(Picinae). If these deep relationships are to be resolved, phylogenomic
approaches may be necessary.
PMID- 26416707
TI - The systematics of carnivorous sponges.
AB - Carnivorous sponges are characterized by their unique method of capturing
mesoplanktonic prey coupled with the complete or partial reduction of the
aquiferous system characteristic of the phylum Porifera. Current systematics
place the vast majority of carnivorous sponges within Cladorhizidae, with certain
species assigned to Guitarridae and Esperiopsidae. Morphological characters have
not been able to show whether this classification is evolutionary accurate, and
whether carnivory has evolved once or in several lineages. In the present paper
we present the first comprehensive molecular phylogeny of the carnivorous
sponges, interpret these results in conjunction with morphological characters,
and propose a revised classification of the group. Molecular phylogenies were
inferred using 18S rDNA and a combined dataset of partial 28S rDNA, COI and ALG11
sequences. The results recovered carnivorous sponges as a clade closely related
to the families Mycalidae and Guitarridae, showing family Cladorhizidae to be
monophyletic and also including carnivorous species currently placed in other
families. The genus Lycopodina is resurrected for species currently placed in the
paraphyletic subgenus Asbestopluma (Asbestopluma) featuring forceps spicules and
lacking sigmas or sigmancistras. The genera Chondrocladia and Cladorhiza are
found to be monophyletic. However, results indicate that the subgenus
Chondrocladia is polyphyletic with respect to the subgenera Meliiderma and
Symmetrocladia. Euchelipluma, formerly Guitarridae, is retained, but transferred
to Cladorhizidae. The four known carnivorous species currently in Esperiopsis are
transferred to Abyssocladia. Neocladia is a junior homonym and is here renamed
Koltunicladia. Our results provide strong evidence in support of the hypothesis
that carnivory in sponges has evolved only once. While spicule characters mostly
reflect monophyletic groups at the generic level, differences between genera
represent evolution within family Cladorhizidae rather than evolution of
carnivory in separate lineages. Conflicting spicule characters can be
reinterpreted to support the inclusion of all carnivorous sponges within
Cladorhizidae, and a carnivorous habit should thus be considered the main
diagnostic character in systematic classification.
PMID- 26416708
TI - Differences in Self-Reported Physical Activity and Body Mass Index Among Older
Hispanic and Non-Hispanic White Men and Women: Findings from the 2009 California
Health Interview Survey.
AB - Older Hispanic Americans are a rapidly growing minority group who are
disproportionately affected by diabetes mellitus and obesity. Given the
importance of physical activity, particularly leisure-time activity, in the
management of diabetes mellitus and obesity, the current study examined ethnic
and sex differences in walking for transportation, leisure-time walking, moderate
activity (not including walking), and vigorous activity between Hispanic and non
Hispanic white (NHW) older adults (age 55 and older) using the 2009 California
Health Interview Survey, a population-based survey representative of California's
noninstitutionalized population. The total sample consisted of 21,702
participants (20,148 NHW (7,968 men, 12,180 women) and 1,554 Hispanic (609 men,
945 women)). Multivariable logistic and linear regression analyses were adjusted
for sociodemographic characteristics. The findings revealed that Hispanic men and
women were significantly less likely to engage in self-reported leisure-time
walking and vigorous activity than NHW men (adjusted odds ratio (aOR) = 0.71, 95%
confidence interval (CI) = 0.51-0.99) and women (aOR = 0.60, 95% CI = 0.42-0.87).
Regardless of ethnic group, men were more likely than women to engage in self
reported walking for transportation (aOR = 0.71, 95% CI = 0.58-0.87), moderate
activity (aOR = 0.68, 95% CI = 0.57-0.81), and vigorous activity (aOR = 0.58, 95%
CI = 0.50-0.68). All types of self-reported physical activity were associated
with lower body mass index (BMI; P < .001), although significant interactions
between sex and leisure time walking (P < .001), moderate activity (P < .001),
and vigorous activity (P < .001) indicated that women who engaged in these
activities reported the lowest BMIs. The findings highlight the importance of
emphasizing walking in efforts to increase moderate and vigorous activity,
particularly for older women.
PMID- 26416709
TI - Removal of simulated biofilm: a preclinical ergonomic comparison of instruments
and operators.
AB - BACKGROUND: Periodontal scaling might cause musculoskeletal disorders, and
scaling instruments might not only have different effectiveness and efficiency
but also differ in their ergonomic properties. The present study assessed
ergonomic working patterns of experienced (EO) and less experienced operators
(LO) when using hand and powered devices for periodontal scaling and root
planning. METHODS: In an experimental study using periodontally affected
manikins, sonic (AIR), ultrasonic (TIG) and hand instruments (GRA) were used by
11 operators (7 EO/4 LO) during simulated supportive periodontal therapy. Using
an electronic motion monitoring system, we objectively assessed the working
frequency and positioning of hand, neck and head. Operators' subjective
evaluation of the instruments was recorded using a questionnaire. RESULTS: Hand
instruments were used with the lowest frequency (2.57 +/- 1.08 s(-1)) but
greatest wrist deviation (59.57 +/- 53.94 degrees ). EO used instruments more
specifically than LO, and generally worked more ergonomically, with less
inclination of head and neck in both the frontal and sagittal planes, especially
when using hand instruments. All groups found hand instruments more tiring and
difficult to use than powered instruments. CONCLUSION: Regardless of operators'
experience, powered instruments were used more ergonomically and were
subjectively preferred compared to hand instruments. CLINICAL RELEVANCE: The use
of hand instruments has potential ergonomic disadvantages. However, with
increasing experience, operators are able to recognise and mitigate possible
risks.
PMID- 26416710
TI - Patients Treated at Low-Volume Centers have Higher Rates of Incomplete Resection
and Compromised Outcomes: Analysis of 31,129 Patients with Papillary Thyroid
Cancer.
AB - BACKGROUND: Data on the importance of margin status after total thyroidectomy for
papillary thyroid cancer (PTC) remain limited. This study sought to identify
factors associated with positive margins and to determine the impact of positive
margins on survival for patients with PTC. METHODS: The National Cancer Data Base
(1998-2006) was queried for patients with PTC who had undergone total
thyroidectomy. The patients were divided into three groups based on margin status
(negative, microscopically positive, and macroscopically positive). Patient
demographic, clinical, and pathologic features were evaluated. A binary logistic
regression model was developed to identify factors associated with positive
margins. A Cox proportional hazards model was developed to identify factors
associated with survival. RESULTS: Of the 31,129 patients enrolled in the study,
91.3 % had negative margins, 8.1 % had microscopically positive margins, and 0.6
% had macroscopically positive margins. The patients with negative margins were
younger and more likely to be female, white, covered by private insurance, and
treated at an academic or high-volume center (p < 0.05). They had smaller tumors
and were less likely to have advanced-stage disease. After multivariable
adjustment, increasing patient age [odds ratio (OR) = 1.02; p < 0.01], government
insurance (OR = 1.20; p < 0.01), and no insurance (OR = 1.34; p = 0.01) were
associated with positive margins. Reception of surgery at a high-volume facility
(OR = 0.72; p < 0.01) was protective. After multivariable adjustment, both
microscopically [hazard ratio (HR), 1.49; p < 0.01] and macroscopically positive
margins (HR = 2.38; p < 0.01) were associated with compromised survival.
CONCLUSIONS: Several vulnerable patient populations have a higher risk of
incomplete resection after thyroidectomy for PTC. High-risk thyroid cancer
patients should be referred to high-volume centers to optimize outcomes.
PMID- 26416711
TI - The Prognostic Significance of Histone Lysine Demethylase JMJD3/KDM6B in
Colorectal Cancer.
AB - BACKGROUND: Jumonji-domain containing 3 (JMJD3) affects transcriptional
regulation by demethylating lysine 27 residue of histone 3. We investigated its
function and prognostic significance in colorectal cancer (CRC). METHODS: The
influence of JMJD3 on cell proliferation was assessed using quantitative RT-PCR
and western blot on the downstream target gene of JMJD3, in knock-down (KD)
experiments and clinical samples from 151 CRC patients. RESULTS: Cells with KD
JMJD3 significantly increased proliferation through cell cycle progression and
apoptosis suppression. Expression of P15INK4B was remarkably decreased in KD
JMJD3 cells; and JMJD3 expression strongly correlated with p15INK4B expression in
clinical CRC samples (P < 0.001, r = 0.566). Low JMJD3 also was an independent
predictor of poor prognosis (P = 0.042) in surgically resected CRC patients.
CONCLUSIONS: JMJD3 has prognostic significance in CRC and mediates p15INK4B
expression. These results imply that elucidation of the JMJD3 role may lead to a
new therapeutic approach for CRC patients.
PMID- 26416713
TI - Compromised Outcome of Papillary Thyroid Cancer at Low-Volume Treatment Centers:
Practice Makes Perfect?
PMID- 26416712
TI - Microcalcifications in 1657 Patients with Pure Ductal Carcinoma in Situ of the
Breast: Correlation with Clinical, Histopathologic, Biologic Features, and Local
Recurrence.
AB - PURPOSE: This study was designed to determine the relationship of
microcalcification morphology and distribution with clinical, histopathologic,
biologic features, and local recurrence (LR) in patients with pure ductal
carcinoma in situ (DCIS) of the breast. METHODS: All patients with pure DCIS who
underwent preoperative mammography at our institution from 1996 through 2009 were
identified. Mammographic findings were classified according to the ACR BI-RADS
lexicon. Associations between mammographic findings and clinical,
histopathologic, biologic characteristics, and LR were analyzed. Statistical
inference used multiple logistic regression and Cox proportional hazards
regression adjusted for age and confounding due to bias from nonrandomized
selection of radiation therapy. RESULTS: We identified 1657 patients with
microcalcifications visualized on mammography. The mean age at diagnosis was 55
years (SD, 11). The mean follow-up was 7 years (range 1-16). Ipsilateral LR was 4
% in segmentectomy (987) and 1.5 % in mastectomy (670) patients. Increased LR
risk was seen in patients with dense breast tissue (p < 0.05) and larger DCIS
size (p < 0.01). Radiation therapy was associated with a 2.8-fold decrease in the
LR risk. Fine linear (branching) microcalcifications were associated with 5.2
fold increase in LR. Extremely dense breast tissue was associated with
positive/close margins (p = 0.04) and multicentricity (p < 0.01). Younger women
were more likely to have extremely dense breast tissue (p < 0.0001), multicentric
disease (p < 0.0004), and undergo mastectomy (p < 0.0001). CONCLUSIONS: Dense
breast tissue, large DCIS size, and fine linear (branching) microcalcifications
were associated with increased LR, yet overall LR rates remained low. Extremely
dense breast tissue was a risk factor for multicentricity and positive margins in
DCIS.
PMID- 26416714
TI - Verification of WFA-Sialylated MUC1 as a Sensitive Biliary Biomarker for Human
Biliary Tract Cancer.
AB - BACKGROUND: The diagnostic accuracy of biliary cytology is limited. A novel
sandwich enzyme-linked immunosorbent assay that combined Wisteria floribunda
agglutinin (WFA) and anti-sialylated mucin 1 (MUC1) monoclonal antibody to target
bile samples was recently developed. This study was designed to verify the
diagnostic accuracy of WFA-sialylated MUC1 as a sensitive biliary biomarker for
human biliary tract cancer. METHODS: Bile samples from 27 patients with benign
disease and 174 patients with biliary tract cancer were analyzed. A receiver
operated characteristic curve analysis for biliary WFA-sialylated MUC1 and serum
CA19-9 levels was performed to determine the cutoff value for the prediction of
the presence of biliary tract cancer. RESULTS: Biliary WFA-sialylated MUC1 levels
were significantly higher in the biliary tract cancer group compared with the
benign group (P < 0.001). The cutoff value of WFA-sialylated MUC1 for
discriminating biliary tract cancer was 10.5. The sensitivity of WFA-sialylated
MUC1 in discriminating biliary tract cancer was much higher (82.2 %) than that of
cytology (23.6 %) when this cutoff value was used. The cutoff value of serum CA19
9 for discriminating biliary tract cancer was 38 IU/L in the same cohort. All
patients with biliary WFA-sialylated MUC1 and serum CA19-9 above the cutoff
values had biliary tract cancer, and no patient with benign disease was
categorized in this group. CONCLUSIONS: Biliary WFA-sialylated MUC1 is a useful
biomarker for the differentiation of biliary tract cancer. The sensitivity of WFA
sialylated MUC1 was clearly higher than that of biliary cytology. Further data
collection is necessary to validate the clinical usefulness of this biomarker.
PMID- 26416715
TI - Prognostic Significance of Neutrophil-to-Lymphocyte Ratio and Platelet-to
Lymphocyte Ratio in Oncologic Outcomes of Esophageal Cancer: A Systematic Review
and Meta-analysis.
AB - BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio
(PLR) have been reported to predict oncologic outcomes in patients with various
types of cancer. However, their prognostic value in patients with esophageal
cancer is unclear. In this meta-analysis, we evaluated the prognostic
significance of NLR and PLR in esophageal cancer patients. METHODS: We performed
comprehensive searches of electronic databases to identify studies that evaluated
the prognostic impact of pretreatment NLR and PLR in esophageal cancer patients.
The end points were overall survival (OS), disease-free survival, and
clinicopathologic parameters. A meta-analysis using random-effects models was
performed to calculate hazard ratios (HRs) or odds ratios with 95 % confidence
intervals (CIs). RESULTS: Seven retrospective, observational, cohort studies
involving 1540 patients were included. All seven studies evaluated NLR, and four
evaluated PLR. Both high NLR (HR 1.40, 95 % CI 1.08-1.81, P = 0.01) and high PLR
(HR 1.59, 95 % CI 1.14-2.21, P = 0.006) were significantly predictive of poorer
OS. NLR was not a significant predictor of disease-free survival. High PLR (HR
1.85, 95 % CI 1.50-2.28, P < 0.00001) but not NLR was significantly predictive of
poorer OS in a subgroup of patients who underwent curative surgery without
neoadjuvant chemoradiation. Both high NLR and high PLR were significantly
associated with deeper tumor invasion and lymph node metastasis. CONCLUSIONS: NLR
and PLR are associated with tumor progression and are predictive of poorer
survival in patients with esophageal cancer. These ratios may thus help to inform
treatment decisions and predict treatment outcomes.
PMID- 26416716
TI - Potential causes of sudden cardiac death in nemaline myopathy.
PMID- 26416718
TI - In the eye of the neutrophil swarm-navigation signals that bring neutrophils
together in inflamed and infected tissues.
AB - Neutrophils are sentinel cells that express in higher vertebrates >30 chemokine
and chemoattractant receptors to sense and quickly react to tissue damage
signals. Intravital microscopy studies in mouse models of wounding, inflammation,
and infection have revealed that neutrophils form cell swarms at local sites of
tissue injury and cell death. This swarming response is choreographed by
chemokines, lipids, and other chemoattractants, controlling sequential phases of
highly coordinated chemotaxis, intercellular signal relay, and cluster formation
among neutrophils. This review will give a brief overview about the basic
principles and key molecules that have led to the refined multistep model of how
neutrophils come together to isolate sites of tissue injury and microbial
invasion from healthy tissue. Whereas auto- and paracrine signaling among
neutrophils during later phases of swarming can provide a level of self
organization for robust navigation in diverse inflammatory settings, guidance
factors from primary tissue lesions, resident bystander cells, and dying cells
regulate the initial phases of the swarming response. This review will discuss
how the specific environmental context and mixture of attractants at the locally
inflamed site can lead to variants of the multistep attraction model and
influence the extent of neutrophil swarming, ranging from accumulations of only
few individual cells to the aggregation of several hundreds of neutrophils, as
found in abscesses. Given the critical roles of neutrophils in both host
protection and tissue destruction, novel insights on neutrophil swarming might
provide useful for the therapeutic modulation of neutrophil-dependent
inflammatory processes.
PMID- 26416717
TI - Sepsis-induced selective parvalbumin interneuron phenotype loss and cognitive
impairments may be mediated by NADPH oxidase 2 activation in mice.
AB - BACKGROUND: Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction
caused by many pathological events, including neuroinflammation and oxidative
stress damage. Increasing evidence suggests that parvalbumin (PV) interneurons
play a key role in the cognitive process, whereas the dysfunction of these
interneurons has been implicated in a number of major psychiatric disorders.
Here, we aimed to investigate whether enhanced inflammation and oxidative stress
mediated PV interneuron phenotype loss plays a role in sepsis-induced cognitive
impairments. METHODS: Male C57BL/6 mice were subjected to cecal ligation and
puncture or sham operation. For the interventional study, the animals were
chronically treated with a nicotinamide adenine dinucleotide phosphate (NADPH)
oxidase inhibitor, apocynin, at 5 mg/kg. The mice were euthanized at the
indicated time points, and the brain tissues were harvested for determination of
the PV, membrane subunit of NADPH oxidase gp91(phox), and markers of oxidative
stress (4-hydroxynonenal and malondialdehyde) and inflammation (tumor necrosis
factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-10). A separate
cohort of animals was used to evaluate the behavioral alterations by the open
field and fear conditioning tests. Primary hippocampal neuronal cultures were
used to investigate the mechanisms underlying the dysfunction of PV interneurons.
RESULTS: Sepsis resulted in cognitive impairments, which was accompanied by
selective phenotype loss of PV interneurons and increased gp91(phox), 4
hydroxynonenal, malondialdehyde, IL-1beta, and IL-6 expressions. Notably, these
abnormalities could be rescued by apocynin treatment. CONCLUSION: Selective
phenotype loss of PV interneurons, as a result of NADPH oxidase 2 (Nox2)
activation, might partly contribute to cognitive impairments in a mouse model of
SAE.
PMID- 26416719
TI - Systematic review and meta-analysis of the sero-epidemiological association
between Epstein-Barr virus and rheumatoid arthritis.
AB - INTRODUCTION: Infection with Epstein-Barr virus (EBV) has been suggested to
contribute to the pathogenesis of autoimmune diseases, including rheumatoid
arthritis (RA). We sought to determine whether prior infection with the virus
occurs more frequently in patients with RA compared to controls. METHODS: We
performed a systematic review and meta-analyses of studies that reported the
prevalence of anti-EBV antibodies in the sera of cases with RA and controls by
searching Medline and Embase databases from 1946 to 2014, with no language
restriction. Mantel-Haenszel odds ratios for the detection of anti-EBV antibodies
were calculated, and meta-analyses conducted. Quality assessments were performed
using a modified version of the Newcastle-Ottawa scale. RESULTS: Twenty-three
studies were included. Quality assessment found most studies reported acceptable
selection criteria but poor descriptions of how cases and controls were
recruited. When all studies were included, there was a statistically significant
higher seroprevalence of anti-VCA IgG in patients with RA compared to controls
with an odds ratio (OR) of 1.61 (95 % confidence interval (CI) 1.05-2.46, p =
0.03), which is a similar-sized summary OR to that reported for systemic lupus
erythematosus (SLE). However, when studies were restricted to those reporting
more plausible levels of exposure to EBV in the control groups, no significant
association was apparent, OR 1.47 (95 % CI 0.88-2.46, p = 0.14). Using anti-EBNA
1 or anti-EA IgG as markers of previous infection also did not yield significant
associations (OR 1.05, 95 % CI 0.68-1.61, p = 0.82; OR 2.2, 95 % CI 0.86-5.65, p
= 0.10 respectively). CONCLUSIONS: Overall, these findings do not demonstrate an
association between EBV seroprevalence and RA and therefore do not support the
hypothesis that prior infection with EBV predisposes to the development of RA.
This contrasts with meta-analyses that indicate EBV infection is associated with
multiple sclerosis and SLE.
PMID- 26416720
TI - The Impact of Fluid Inertia on In Vivo Estimation of Mitral Valve Leaflet
Constitutive Properties and Mechanics.
AB - We examine the influence of the added mass effect (fluid inertia) on mitral valve
leaflet stress during isovolumetric phases. To study this effect, oscillating
flow is applied to a flexible membrane at various frequencies to control inertia.
Resulting membrane strain is calculated through a three-dimensional
reconstruction of markers from stereo images. To investigate the effect in vivo,
the analysis is repeated on a published dataset for an ovine mitral valve
(Journal of Biomechanics 42(16): 2697-2701). The membrane experiment demonstrates
that the relationship between pressure and strain must be corrected with a fluid
inertia term if the ratio of inertia to pressure differential approaches 1. In
the mitral valve, this ratio reaches 0.7 during isovolumetric contraction for an
acceleration of 6 m/s(2). Acceleration is reduced by 72% during isovolumetric
relaxation. Fluid acceleration also varies along the leaflet during isovolumetric
phases, resulting in spatial variations in stress. These results demonstrate that
fluid inertia may be the source of the temporally and spatially varying stiffness
measurements previously seen through inverse finite element analysis of in vivo
data during isovolumetric phases. This study demonstrates that there is a need to
account for added mass effects when analyzing in vivo constitutive relationships
of heart valves.
PMID- 26416722
TI - MicroRNAs in obesity-associated disorders.
AB - The emergence of a worldwide obesity epidemic has dramatically increased the
prevalence of insulin resistance and metabolic syndrome, predisposing individuals
to a greater risk for the development of non-alcoholic fatty liver disease, type
II diabetes and atherosclerotic cardiovascular diseases. Current available
pharmacological interventions combined with diet and exercise-based managements
are still poorly effective for weight management, likely in part due to an
incomplete understanding of regulatory mechanisms and pathways contributing to
the systemic metabolic abnormalities under disturbed energy homeostasis.
MicroRNAs, small non-coding RNAs that regulate posttranscriptional gene
expression, have been increasingly described to influence shifts in metabolic
pathways under various obesity-related disease settings. Here we review recent
discoveries of the mechanistic role that microRNAs play in regulating metabolic
functions in liver and adipose tissues involved in obesity associated disorders,
and briefly discusses the potential candidates that are being pursued as viable
therapeutic targets.
PMID- 26416721
TI - The Incompatibility of Living Systems: Characterizing Growth-Induced
Incompatibilities in Expanded Skin.
AB - Skin expansion is a common surgical technique to correct large cutaneous defects.
Selecting a successful expansion protocol is solely based on the experience and
personal preference of the operating surgeon. Skin expansion could be improved by
predictive computational simulations. Towards this goal, we model skin expansion
using the continuum framework of finite growth. This approach crucially relies on
the concept of incompatible configurations. However, aside from the classical
opening angle experiment, our current understanding of growth-induced
incompatibilities remains rather vague. Here we visualize and characterize
incompatibilities in living systems using skin expansion in a porcine model: We
implanted and inflated two expanders, crescent, and spherical, and filled them to
225 cc throughout a period of 21 days. To quantify the residual strains developed
during this period, we excised the expanded skin patches and subdivided them into
smaller pieces. Skin growth averaged 1.17 times the original area for the
spherical and 1.10 for the crescent expander, and displayed significant regional
variations. When subdivided into smaller pieces, the grown skin patches retracted
heterogeneously and confirmed the existence of incompatibilities. Understanding
skin growth through mechanical stretch will allow surgeons to improve-and
ultimately personalize-preoperative treatment planning in plastic and
reconstructive surgery.
PMID- 26416723
TI - Development of a Magnetic Attachment Method for Bionic Eye Applications.
AB - Successful visual prostheses require stable, long-term attachment. Epiretinal
prostheses, in particular, require attachment methods to fix the prosthesis onto
the retina. The most common method is fixation with a retinal tack; however,
tacks cause retinal trauma, and surgical proficiency is important to ensure
optimal placement of the prosthesis near the macula. Accordingly, alternate
attachment methods are required. In this study, we detail a novel method of
magnetic attachment for an epiretinal prosthesis using two prostheses components
positioned on opposing sides of the retina. The magnetic attachment technique was
piloted in a feline animal model (chronic, nonrecovery implantation). We also
detail a new method to reliably control the magnet coupling force using heat. It
was found that the force exerted upon the tissue that separates the two
components could be minimized as the measured force is proportionately smaller at
the working distance. We thus detail, for the first time, a surgical method using
customized magnets to position and affix an epiretinal prosthesis on the retina.
The position of the epiretinal prosthesis is reliable, and its location on the
retina is accurately controlled by the placement of a secondary magnet in the
suprachoroidal location. The electrode position above the retina is less than 50
microns at the center of the device, although there were pressure points seen at
the two edges due to curvature misalignment. The degree of retinal compression
found in this study was unacceptably high; nevertheless, the normal structure of
the retina remained intact under the electrodes.
PMID- 26416724
TI - Exploring cardio-pulmonary interactions by examining the ventilatory, pulmonary
gas exchange, and heart rate kinetics response to high-intensity cycle exercise
in COPD patients.
PMID- 26416725
TI - Implementation and development of early intervention in psychosis services in
Italy: a national survey promoted by the Associazione Italiana Interventi Precoci
nelle Psicosi.
AB - AIM: This is the first comprehensive, nationwide survey aimed at collecting
evidence about the process of implementation and development of early
intervention in psychosis (EIP) services (EIPs) in Italy, following the
establishment of the pilot program 'Programma 2000' in 1999 and the publishing of
the Italian National Guidelines in 2007. This survey covers all the Departments
of Mental Health (DMHs) operating in Italy in 2013. METHODS: Using a purpose
designed form to assess EIP implementation, all directors of public mental health
services for adults throughout Italy (n = 216) were asked to provide information
about the activities of EIP-relevant local services. The initial delivery was
followed by a request for a prompt response. RESULTS: Out of 216 enquired DMHs,
103 provided computable answers to the survey (response rate = 48%). Among
responders, 45 (44%) reported the implementation of EIP (one out of five DMHs
operating in Italy). About a half of the active EIPs also targeted patients at
ultra-high risk of psychosis (n = 27). Strict application of guidelines related
to drug prescription was reported in 35% of EIPs. Conversely, 90% provided some
kind of structured psychotherapy and psychoeducation. Among EIPs, a minority
reported willingness to provide initial assessment/contact at the patient's home.
CONCLUSION: Albeit slowly, the implementation of EIP is spreading throughout the
Italian public network of mental health. There is still a wide variability in the
distribution of EIP services across the Italian territory. Further efforts are
necessary to stimulate policy endorsement and resource allocation, as well as to
support the poorest zones.
PMID- 26416726
TI - Development of 'Redox Arrays' for identifying novel glutathionylated proteins in
the secretome.
AB - Proteomics techniques for analysing the redox status of individual proteins in
complex mixtures tend to identify the same proteins due to their high abundance.
We describe here an array-based technique to identify proteins undergoing
glutathionylation and apply it to the secretome and the proteome of human
monocytic cells. The method is based on incorporation of biotinylated glutathione
(GSH) into proteins, which can then be identified following binding to a 1000
protein antibody array. We thus identify 38 secreted and 55 intracellular
glutathionylated proteins, most of which are novel candidates for
glutathionylation. Two of the proteins identified in these experiments, IL-1 sRII
and Lyn, were then confirmed to be susceptible to glutathionylation. Comparison
of the redox array with conventional proteomic methods confirmed that the redox
array is much more sensitive, and can be performed using more than 100-fold less
protein than is required for methods based on mass spectrometry. The
identification of novel targets of glutathionylation, particularly in the
secretome where the protein concentration is much lower, shows that redox arrays
can overcome some of the limitations of established redox proteomics techniques.
PMID- 26416727
TI - Identification of carbohydrate anomers using ion mobility-mass spectrometry.
AB - Carbohydrates are ubiquitous biological polymers that are important in a broad
range of biological processes. However, owing to their branched structures and
the presence of stereogenic centres at each glycosidic linkage between monomers,
carbohydrates are harder to characterize than are peptides and oligonucleotides.
Methods such as nuclear magnetic resonance spectroscopy can be used to
characterize glycosidic linkages, but this technique requires milligram amounts
of material and cannot detect small amounts of coexisting isomers. Mass
spectrometry, on the other hand, can provide information on carbohydrate
composition and connectivity for even small amounts of sample, but it cannot be
used to distinguish between stereoisomers. Here, we demonstrate that ion mobility
mass spectrometry--a method that separates molecules according to their mass,
charge, size, and shape--can unambiguously identify carbohydrate linkage-isomers
and stereoisomers. We analysed six synthetic carbohydrate isomers that differ in
composition, connectivity, or configuration. Our data show that coexisting
carbohydrate isomers can be identified, and relative concentrations of the minor
isomer as low as 0.1 per cent can be detected. In addition, the analysis is
rapid, and requires no derivatization and only small amounts of sample. These
results indicate that ion mobility-mass spectrometry is an effective tool for the
analysis of complex carbohydrates. This method could have an impact on the field
of carbohydrate synthesis similar to that of the advent of high-performance
liquid chromatography on the field of peptide assembly in the late 1970s.
PMID- 26416729
TI - Crystal structure of human glycine receptor-alpha3 bound to antagonist
strychnine.
AB - Neurotransmitter-gated ion channels of the Cys-loop receptor family are essential
mediators of fast neurotransmission throughout the nervous system and are
implicated in many neurological disorders. Available X-ray structures of
prokaryotic and eukaryotic Cys-loop receptors provide tremendous insights into
the binding of agonists, the subsequent opening of the ion channel, and the
mechanism of channel activation. Yet the mechanism of inactivation by antagonists
remains unknown. Here we present a 3.0 A X-ray structure of the human glycine
receptor-alpha3 homopentamer in complex with a high affinity, high-specificity
antagonist, strychnine. Our structure allows us to explore in detail the
molecular recognition of antagonists. Comparisons with previous structures reveal
a mechanism for antagonist-induced inactivation of Cys-loop receptors, involving
an expansion of the orthosteric binding site in the extracellular domain that is
coupled to closure of the ion pore in the transmembrane domain.
PMID- 26416730
TI - Two independent and primitive envelopes of the bilobate nucleus of comet 67P.
AB - The factors shaping cometary nuclei are still largely unknown, but could be the
result of concurrent effects of evolutionary and primordial processes. The
peculiar bilobed shape of comet 67P/Churyumov-Gerasimenko may be the result of
the fusion of two objects that were once separate or the result of a localized
excavation by outgassing at the interface between the two lobes. Here we report
that the comet's major lobe is enveloped by a nearly continuous set of strata, up
to 650 metres thick, which are independent of an analogous stratified envelope on
the minor lobe. Gravity vectors computed for the two lobes separately are closer
to perpendicular to the strata than those calculated for the entire nucleus and
adjacent to the neck separating the two lobes. Therefore comet 67P/Churyumov
Gerasimenko is an accreted body of two distinct objects with 'onion-like'
stratification, which formed before they merged. We conclude that gentle, low
velocity collisions occurred between two fully formed kilometre-sized
cometesimals in the early stages of the Solar System. The notable structural
similarities between the two lobes of comet 67P/Churyumov-Gerasimenko indicate
that the early-forming cometesimals experienced similar primordial stratified
accretion, even though they formed independently.
PMID- 26416731
TI - Plasticity-driven individualization of olfactory coding in mushroom body output
neurons.
AB - Although all sensory circuits ascend to higher brain areas where stimuli are
represented in sparse, stimulus-specific activity patterns, relatively little is
known about sensory coding on the descending side of neural circuits, as a
network converges. In insects, mushroom bodies have been an important model
system for studying sparse coding in the olfactory system, where this format is
important for accurate memory formation. In Drosophila, it has recently been
shown that the 2,000 Kenyon cells of the mushroom body converge onto a population
of only 34 mushroom body output neurons (MBONs), which fall into 21 anatomically
distinct cell types. Here we provide the first, to our knowledge, comprehensive
view of olfactory representations at the fourth layer of the circuit, where we
find a clear transition in the principles of sensory coding. We show that MBON
tuning curves are highly correlated with one another. This is in sharp contrast
to the process of progressive decorrelation of tuning in the earlier layers of
the circuit. Instead, at the population level, odour representations are
reformatted so that positive and negative correlations arise between
representations of different odours. At the single-cell level, we show that
uniquely identifiable MBONs display profoundly different tuning across different
animals, but that tuning of the same neuron across the two hemispheres of an
individual fly was nearly identical. Thus, individualized coordination of tuning
arises at this level of the olfactory circuit. Furthermore, we find that this
individualization is an active process that requires a learning-related gene,
rutabaga. Ultimately, neural circuits have to flexibly map highly stimulus
specific information in sparse layers onto a limited number of different motor
outputs. The reformatting of sensory representations we observe here may mark the
beginning of this sensory-motor transition in the olfactory system.
PMID- 26416728
TI - The soft palate is an important site of adaptation for transmissible influenza
viruses.
AB - Influenza A viruses pose a major public health threat by causing seasonal
epidemics and sporadic pandemics. Their epidemiological success relies on
airborne transmission from person to person; however, the viral properties
governing airborne transmission of influenza A viruses are complex. Influenza A
virus infection is mediated via binding of the viral haemagglutinin (HA) to
terminally attached alpha2,3 or alpha2,6 sialic acids on cell surface
glycoproteins. Human influenza A viruses preferentially bind alpha2,6-linked
sialic acids whereas avian influenza A viruses bind alpha2,3-linked sialic acids
on complex glycans on airway epithelial cells. Historically, influenza A viruses
with preferential association with alpha2,3-linked sialic acids have not been
transmitted efficiently by the airborne route in ferrets. Here we observe
efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus
(A/California/07/2009) engineered to preferentially bind alpha2,3-linked sialic
acids. Airborne transmission was associated with rapid selection of virus with a
change at a single HA site that conferred binding to long-chain alpha2,6-linked
sialic acids, without loss of alpha2,3-linked sialic acid binding. The
transmissible virus emerged in experimentally infected ferrets within 24 hours
after infection and was remarkably enriched in the soft palate, where long-chain
alpha2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably,
presence of long-chain alpha2,6-linked sialic acids is conserved in ferret, pig
and human soft palate. Using a loss-of-function approach with this one virus, we
demonstrate that the ferret soft palate, a tissue not normally sampled in animal
models of influenza, rapidly selects for transmissible influenza A viruses with
human receptor (alpha2,6-linked sialic acids) preference.
PMID- 26416732
TI - The genomic landscape of response to EGFR blockade in colorectal cancer.
AB - Colorectal cancer is the third most common cancer worldwide, with 1.2 million
patients diagnosed annually. In late-stage colorectal cancer, the most commonly
used targeted therapies are the monoclonal antibodies cetuximab and panitumumab,
which prevent epidermal growth factor receptor (EGFR) activation. Recent studies
have identified alterations in KRAS and other genes as likely mechanisms of
primary and secondary resistance to anti-EGFR antibody therapy. Despite these
efforts, additional mechanisms of resistance to EGFR blockade are thought to be
present in colorectal cancer and little is known about determinants of
sensitivity to this therapy. To examine the effect of somatic genetic changes in
colorectal cancer on response to anti-EGFR antibody therapy, here we perform
complete exome sequence and copy number analyses of 129 patient-derived tumour
grafts and targeted genomic analyses of 55 patient tumours, all of which were
KRAS wild-type. We analysed the response of tumours to anti-EGFR antibody
blockade in tumour graft models and in clinical settings and functionally linked
therapeutic responses to mutational data. In addition to previously identified
genes, we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as
potential mechanisms of primary resistance to this therapy. Novel alterations in
the ectodomain of EGFR were identified in patients with acquired resistance to
EGFR blockade. Amplifications and sequence changes in the tyrosine kinase
receptor adaptor gene IRS2 were identified in tumours with increased sensitivity
to anti-EGFR therapy. Therapeutic resistance to EGFR blockade could be overcome
in tumour graft models through combinatorial therapies targeting actionable
genes. These analyses provide a systematic approach to evaluating response to
targeted therapies in human cancer, highlight new mechanisms of responsiveness to
anti-EGFR therapies, and delineate new avenues for intervention in managing
colorectal cancer.
PMID- 26416733
TI - SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef.
AB - HIV-1 Nef and the unrelated mouse leukaemia virus glycosylated Gag (glycoGag)
strongly enhance the infectivity of HIV-1 virions produced in certain cell types
in a clathrin-dependent manner. Here we show that Nef and glycoGag prevent the
incorporation of the multipass transmembrane proteins serine incorporator 3
(SERINC3) and SERINC5 into HIV-1 virions to an extent that correlates with
infectivity enhancement. Silencing of both SERINC3 and SERINC5 precisely
phenocopied the effects of Nef and glycoGag on HIV-1 infectivity. The infectivity
of nef-deficient virions increased more than 100-fold when produced in double
knockout human CD4(+) T cells that lack both SERINC3 and SERINC5, and re
expression experiments confirmed that the absence of SERINC3 and SERINC5
accounted for the infectivity enhancement. Furthermore, SERINC3 and SERINC5
together restricted HIV-1 replication, and this restriction was evaded by Nef.
SERINC3 and SERINC5 are highly expressed in primary human HIV-1 target cells, and
inhibiting their downregulation by Nef is a potential strategy to combat
HIV/AIDS.
PMID- 26416734
TI - HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation.
AB - HIV-1 Nef, a protein important for the development of AIDS, has well
characterized effects on host membrane trafficking and receptor downregulation.
By an unidentified mechanism, Nef increases the intrinsic infectivity of HIV-1
virions in a host-cell-dependent manner. Here we identify the host transmembrane
protein SERINC5, and to a lesser extent SERINC3, as a potent inhibitor of HIV-1
particle infectivity that is counteracted by Nef. SERINC5 localizes to the plasma
membrane, where it is efficiently incorporated into budding HIV-1 virions and
impairs subsequent virion penetration of susceptible target cells. Nef redirects
SERINC5 to a Rab7-positive endosomal compartment and thereby excludes it from HIV
1 particles. The ability to counteract SERINC5 was conserved in Nef encoded by
diverse primate immunodeficiency viruses, as well as in the structurally
unrelated glycosylated Gag from murine leukaemia virus. These examples of
functional conservation and convergent evolution emphasize the fundamental
importance of SERINC5 as a potent anti-retroviral factor.
PMID- 26416736
TI - Erratum: Structural imprints in vivo decode RNA regulatory mechanisms.
PMID- 26416737
TI - Corrigendum: Improving survival by exploiting tumour dependence on stabilized
mutant p53 for treatment.
PMID- 26416735
TI - Structure and mechanism of the mammalian fructose transporter GLUT5.
AB - The altered activity of the fructose transporter GLUT5, an isoform of the
facilitated-diffusion glucose transporter family, has been linked to disorders
such as type 2 diabetes and obesity. GLUT5 is also overexpressed in certain
tumour cells, and inhibitors are potential drugs for these conditions. Here we
describe the crystal structures of GLUT5 from Rattus norvegicus and Bos taurus in
open outward- and open inward-facing conformations, respectively. GLUT5 has a
major facilitator superfamily fold like other homologous monosaccharide
transporters. On the basis of a comparison of the inward-facing structures of
GLUT5 and human GLUT1, a ubiquitous glucose transporter, we show that a single
point mutation is enough to switch the substrate-binding preference of GLUT5 from
fructose to glucose. A comparison of the substrate-free structures of GLUT5 with
occluded substrate-bound structures of Escherichia coli XylE suggests that, in
addition to global rocker-switch-like re-orientation of the bundles, local
asymmetric rearrangements of carboxy-terminal transmembrane bundle helices TM7
and TM10 underlie a 'gated-pore' transport mechanism in such monosaccharide
transporters.
PMID- 26416738
TI - Non-coding RNA: Antibiotic tricks a switch.
PMID- 26416739
TI - Phenology: Spring greening in a warming world.
PMID- 26416741
TI - Corrigendum: Cleavage of CAD inhibitor in CAD activation and DNA degradation
during apoptosis.
PMID- 26416740
TI - Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins.
AB - The battle for survival between bacteria and the viruses that infect them
(phages) has led to the evolution of many bacterial defence systems and phage
encoded antagonists of these systems. Clustered regularly interspaced short
palindromic repeats (CRISPR) and the CRISPR-associated (cas) genes comprise an
adaptive immune system that is one of the most widespread means by which bacteria
defend themselves against phages. We identified the first examples of proteins
produced by phages that inhibit a CRISPR-Cas system. Here we performed
biochemical and in vivo investigations of three of these anti-CRISPR proteins,
and show that each inhibits CRISPR-Cas activity through a distinct mechanism. Two
block the DNA-binding activity of the CRISPR-Cas complex, yet do this by
interacting with different protein subunits, and using steric or non-steric modes
of inhibition. The third anti-CRISPR protein operates by binding to the Cas3
helicase-nuclease and preventing its recruitment to the DNA-bound CRISPR-Cas
complex. In vivo, this anti-CRISPR can convert the CRISPR-Cas system into a
transcriptional repressor, providing the first example-to our knowledge-of
modulation of CRISPR-Cas activity by a protein interactor. The diverse sequences
and mechanisms of action of these anti-CRISPR proteins imply an independent
evolution, and foreshadow the existence of other means by which proteins may
alter CRISPR-Cas function.
PMID- 26416742
TI - Erratum: Mechanism of phospho-ubiquitin-induced PARKIN activation.
PMID- 26416743
TI - Neurobiology: Individuality sniffed out in flies.
PMID- 26416745
TI - Corrigendum: Biocontainment of genetically modified organisms by synthetic
protein design.
PMID- 26416744
TI - Deep imaging of bone marrow shows non-dividing stem cells are mainly
perisinusoidal.
AB - Haematopoietic stem cells (HSCs) reside in a perivascular niche but the specific
location of this niche remains controversial. HSCs are rare and few can be found
in thin tissue sections or upon live imaging, making it difficult to
comprehensively localize dividing and non-dividing HSCs. Here, using a green
fluorescent protein (GFP) knock-in for the gene Ctnnal1 in mice (hereafter
denoted as alpha-catulin(GFP)), we discover that alpha-catulin(GFP) is expressed
by only 0.02% of bone marrow haematopoietic cells, including almost all HSCs. We
find that approximately 30% of alpha-catulin-GFP(+)c-kit(+) cells give long-term
multilineage reconstitution of irradiated mice, indicating that alpha-catulin
GFP(+)c-kit(+) cells are comparable in HSC purity to cells obtained using the
best markers currently available. We optically cleared the bone marrow to perform
deep confocal imaging, allowing us to image thousands of alpha-catulin-GFP(+)c
kit(+) cells and to digitally reconstruct large segments of bone marrow. The
distribution of alpha-catulin-GFP(+)c-kit(+) cells indicated that HSCs were more
common in central marrow than near bone surfaces, and in the diaphysis relative
to the metaphysis. Nearly all HSCs contacted leptin receptor positive (Lepr(+))
and Cxcl12(high) niche cells, and approximately 85% of HSCs were within 10 MUm of
a sinusoidal blood vessel. Most HSCs, both dividing (Ki-67(+)) and non-dividing
(Ki-67(-)), were distant from arterioles, transition zone vessels, and bone
surfaces. Dividing and non-dividing HSCs thus reside mainly in perisinusoidal
niches with Lepr(+)Cxcl12(high) cells throughout the bone marrow.
PMID- 26416746
TI - Declining global warming effects on the phenology of spring leaf unfolding.
AB - Earlier spring leaf unfolding is a frequently observed response of plants to
climate warming. Many deciduous tree species require chilling for dormancy
release, and warming-related reductions in chilling may counteract the advance of
leaf unfolding in response to warming. Empirical evidence for this, however, is
limited to saplings or twigs in climate-controlled chambers. Using long-term in
situ observations of leaf unfolding for seven dominant European tree species at
1,245 sites, here we show that the apparent response of leaf unfolding to climate
warming (ST, expressed in days advance of leaf unfolding per degrees C warming)
has significantly decreased from 1980 to 2013 in all monitored tree species.
Averaged across all species and sites, ST decreased by 40% from 4.0 +/- 1.8 days
degrees C(-1) during 1980-1994 to 2.3 +/- 1.6 days degrees C(-1) during 1999
2013. The declining ST was also simulated by chilling-based phenology models,
albeit with a weaker decline (24-30%) than observed in situ. The reduction in ST
is likely to be partly attributable to reduced chilling. Nonetheless, other
mechanisms may also have a role, such as 'photoperiod limitation' mechanisms that
may become ultimately limiting when leaf unfolding dates occur too early in the
season. Our results provide empirical evidence for a declining ST, but also
suggest that the predicted strong winter warming in the future may further reduce
ST and therefore result in a slowdown in the advance of tree spring phenology.
PMID- 26416747
TI - In situ structural analysis of the human nuclear pore complex.
AB - Nuclear pore complexes are fundamental components of all eukaryotic cells that
mediate nucleocytoplasmic exchange. Determining their 110-megadalton structure
imposes a formidable challenge and requires in situ structural biology
approaches. Of approximately 30 nucleoporins (Nups), 15 are structured and form
the Y and inner-ring complexes. These two major scaffolding modules assemble in
multiple copies into an eight-fold rotationally symmetric structure that fuses
the inner and outer nuclear membranes to form a central channel of ~60 nm in
diameter. The scaffold is decorated with transport-channel Nups that often
contain phenylalanine-repeat sequences and mediate the interaction with cargo
complexes. Although the architectural arrangement of parts of the Y complex has
been elucidated, it is unclear how exactly it oligomerizes in situ. Here we
combine cryo-electron tomography with mass spectrometry, biochemical analysis,
perturbation experiments and structural modelling to generate, to our knowledge,
the most comprehensive architectural model of the human nuclear pore complex to
date. Our data suggest previously unknown protein interfaces across Y complexes
and to inner-ring complex members. We show that the transport-channel Nup358
(also known as Ranbp2) has a previously unanticipated role in Y-complex
oligomerization. Our findings blur the established boundaries between scaffold
and transport-channel Nups. We conclude that, similar to coated vesicles, several
copies of the same structural building block--although compositionally identical-
engage in different local sets of interactions and conformations.
PMID- 26416748
TI - Single-cell analysis reveals a stem-cell program in human metastatic breast
cancer cells.
AB - Despite major advances in understanding the molecular and genetic basis of
cancer, metastasis remains the cause of >90% of cancer-related mortality.
Understanding metastasis initiation and progression is critical to developing new
therapeutic strategies to treat and prevent metastatic disease. Prevailing
theories hypothesize that metastases are seeded by rare tumour cells with unique
properties, which may function like stem cells in their ability to initiate and
propagate metastatic tumours. However, the identity of metastasis-initiating
cells in human breast cancer remains elusive, and whether metastases are
hierarchically organized is unknown. Here we show at the single-cell level that
early stage metastatic cells possess a distinct stem-like gene expression
signature. To identify and isolate metastatic cells from patient-derived
xenograft models of human breast cancer, we developed a highly sensitive
fluorescence-activated cell sorting (FACS)-based assay, which allowed us to
enumerate metastatic cells in mouse peripheral tissues. We compared gene
signatures in metastatic cells from tissues with low versus high metastatic
burden. Metastatic cells from low-burden tissues were distinct owing to their
increased expression of stem cell, epithelial-to-mesenchymal transition, pro
survival, and dormancy-associated genes. By contrast, metastatic cells from high
burden tissues were similar to primary tumour cells, which were more
heterogeneous and expressed higher levels of luminal differentiation genes.
Transplantation of stem-like metastatic cells from low-burden tissues showed that
they have considerable tumour-initiating capacity, and can differentiate to
produce luminal-like cancer cells. Progression to high metastatic burden was
associated with increased proliferation and MYC expression, which could be
attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These
findings support a hierarchical model for metastasis, in which metastases are
initiated by stem-like cells that proliferate and differentiate to produce
advanced metastatic disease.
PMID- 26416750
TI - HIV: Antiviral action countered by Nef.
PMID- 26416751
TI - Erratum: IgG1 protects against renal disease in a mouse model of
cryoglobulinaemia.
PMID- 26416749
TI - Mediator kinase inhibition further activates super-enhancer-associated genes in
AML.
AB - Super-enhancers (SEs), which are composed of large clusters of enhancers densely
loaded with the Mediator complex, transcription factors and chromatin regulators,
drive high expression of genes implicated in cell identity and disease, such as
lineage-controlling transcription factors and oncogenes. BRD4 and CDK7 are
positive regulators of SE-mediated transcription. By contrast, negative
regulators of SE-associated genes have not been well described. Here we show that
the Mediator-associated kinases cyclin-dependent kinase 8 (CDK8) and CDK19
restrain increased activation of key SE-associated genes in acute myeloid
leukaemia (AML) cells. We report that the natural product cortistatin A (CA)
selectively inhibits Mediator kinases, has anti-leukaemic activity in vitro and
in vivo, and disproportionately induces upregulation of SE-associated genes in CA
sensitive AML cell lines but not in CA-insensitive cell lines. In AML cells, CA
upregulated SE-associated genes with tumour suppressor and lineage-controlling
functions, including the transcription factors CEBPA, IRF8, IRF1 and ETV6 (refs 6
8). The BRD4 inhibitor I-BET151 downregulated these SE-associated genes, yet also
has anti-leukaemic activity. Individually increasing or decreasing the expression
of these transcription factors suppressed AML cell growth, providing evidence
that leukaemia cells are sensitive to the dosage of SE-associated genes. Our
results demonstrate that Mediator kinases can negatively regulate SE-associated
gene expression in specific cell types, and can be pharmacologically targeted as
a therapeutic approach to AML.
PMID- 26416752
TI - New genomic and fossil data illuminate the origin of enamel.
AB - Enamel, the hardest vertebrate tissue, covers the teeth of almost all
sarcopterygians (lobe-finned bony fishes and tetrapods) as well as the scales and
dermal bones of many fossil lobe-fins. Enamel deposition requires an organic
matrix containing the unique enamel matrix proteins (EMPs) amelogenin (AMEL),
enamelin (ENAM) and ameloblastin (AMBN). Chondrichthyans (cartilaginous fishes)
lack both enamel and EMP genes. Many fossil and a few living non-teleost
actinopterygians (ray-finned bony fishes) such as the gar, Lepisosteus, have
scales and dermal bones covered with a proposed enamel homologue called ganoine.
However, no gene or transcript data for EMPs have been described from
actinopterygians. Here we show that Psarolepis romeri, a bony fish from the the
Early Devonian period, combines enamel-covered dermal odontodes on scales and
skull bones with teeth of naked dentine, and that Lepisosteus oculatus (the
spotted gar) has enam and ambn genes that are expressed in the skin, probably
associated with ganoine formation. The genetic evidence strengthens the
hypothesis that ganoine is homologous with enamel. The fossil evidence, further
supported by the Silurian bony fish Andreolepis, which has enamel-covered scales
but teeth and odontodes on its dermal bones made of naked dentine, indicates that
this tissue originated on the dermal skeleton, probably on the scales. It
subsequently underwent heterotopic expansion across two highly conserved
patterning boundaries (scales/head-shoulder and dermal/oral) within the odontode
skeleton.
PMID- 26416753
TI - Selective small-molecule inhibition of an RNA structural element.
AB - Riboswitches are non-coding RNA structures located in messenger RNAs that bind
endogenous ligands, such as a specific metabolite or ion, to regulate gene
expression. As such, riboswitches serve as a novel, yet largely unexploited,
class of emerging drug targets. Demonstrating this potential, however, has proven
difficult and is restricted to structurally similar antimetabolites and semi
synthetic analogues of their cognate ligand, thus greatly restricting the
chemical space and selectivity sought for such inhibitors. Here we report the
discovery and characterization of ribocil, a highly selective chemical modulator
of bacterial riboflavin riboswitches, which was identified in a phenotypic screen
and acts as a structurally distinct synthetic mimic of the natural ligand, flavin
mononucleotide, to repress riboswitch-mediated ribB gene expression and inhibit
bacterial cell growth. Our findings indicate that non-coding RNA structural
elements may be more broadly targeted by synthetic small molecules than
previously expected.
PMID- 26416754
TI - Structural basis for gene regulation by a B12-dependent photoreceptor.
AB - Photoreceptor proteins enable organisms to sense and respond to light. The newly
discovered CarH-type photoreceptors use a vitamin B12 derivative,
adenosylcobalamin, as the light-sensing chromophore to mediate light-dependent
gene regulation. Here we present crystal structures of Thermus thermophilus CarH
in all three relevant states: in the dark, both free and bound to operator DNA,
and after light exposure. These structures provide visualizations of how
adenosylcobalamin mediates CarH tetramer formation in the dark, how this tetramer
binds to the promoter -35 element to repress transcription, and how light
exposure leads to a large-scale conformational change that activates
transcription. In addition to the remarkable functional repurposing of
adenosylcobalamin from an enzyme cofactor to a light sensor, we find that nature
also repurposed two independent protein modules in assembling CarH. These results
expand the biological role of vitamin B12 and provide fundamental insight into a
new mode of light-dependent gene regulation.
PMID- 26416755
TI - Binding of dinitrogen to an iron-sulfur-carbon site.
AB - Nitrogenases are the enzymes by which certain microorganisms convert atmospheric
dinitrogen (N2) to ammonia, thereby providing essential nitrogen atoms for higher
organisms. The most common nitrogenases reduce atmospheric N2 at the FeMo
cofactor, a sulfur-rich iron-molybdenum cluster (FeMoco). The central iron sites
that are coordinated to sulfur and carbon atoms in FeMoco have been proposed to
be the substrate binding sites, on the basis of kinetic and spectroscopic
studies. In the resting state, the central iron sites each have bonds to three
sulfur atoms and one carbon atom. Addition of electrons to the resting state
causes the FeMoco to react with N2, but the geometry and bonding environment of
N2-bound species remain unknown. Here we describe a synthetic complex with a
sulfur-rich coordination sphere that, upon reduction, breaks an Fe-S bond and
binds N2. The product is the first synthetic Fe-N2 complex in which iron has
bonds to sulfur and carbon atoms, providing a model for N2 coordination in the
FeMoco. Our results demonstrate that breaking an Fe-S bond is a chemically
reasonable route to N2 binding in the FeMoco, and show structural and
spectroscopic details for weakened N2 on a sulfur-rich iron site.
PMID- 26416756
TI - Corrigendum: Recoded organisms engineered to depend on synthetic amino acids.
PMID- 26416760
TI - Quantitative single molecule FRET efficiencies using TIRF microscopy.
AB - Forster resonance energy transfer (FRET) microscopy at the single molecule level
has the potential to yield information on intra and intermolecular distances
within the 2-10 nm range of molecules or molecular complexes that undergo
frequent conformation changes. A pre-requirement for obtaining accurate distance
information is to determine quantitative instrument independent FRET efficiency
values. Here, we applied and evaluated a procedure to determine quantitative FRET
efficiencies directly from individual fluorescence time traces of surface
immobilized DNA molecules without the need for external calibrants. To probe the
robustness of the approach over a wide range of FRET efficiencies we used a set
of doubly labelled double stranded DNA samples, where the acceptor position was
varied systematically. Interestingly, we found that fluorescence contributions
arising from direct acceptor excitation following donor excitation are
intrinsically taken into account in these conditions as other correction factors
can compensate for inaccurate values of these parameters. We give here
guidelines, that can be used through tools within the iSMS software (), for
determining quantitative FRET and assess uncertainties linked with the procedure.
Our results provide insights into the experimental parameters governing
quantitative FRET determination, which is essential for obtaining accurate
structural information from a wide range of biomolecules.
PMID- 26416758
TI - Inhibition of Gli1 mobilizes endogenous neural stem cells for remyelination.
AB - Enhancing repair of myelin is an important but still elusive therapeutic goal in
many neurological disorders. In multiple sclerosis, an inflammatory demyelinating
disease, endogenous remyelination does occur but is frequently insufficient to
restore function. Both parenchymal oligodendrocyte progenitor cells and
endogenous adult neural stem cells resident within the subventricular zone are
known sources of remyelinating cells. Here we characterize the contribution to
remyelination of a subset of adult neural stem cells, identified by their
expression of Gli1, a transcriptional effector of the sonic hedgehog pathway. We
show that these cells are recruited from the subventricular zone to populate
demyelinated lesions in the forebrain but never enter healthy, white matter
tracts. Unexpectedly, recruitment of this pool of neural stem cells, and their
differentiation into oligodendrocytes, is significantly enhanced by genetic or
pharmacological inhibition of Gli1. Importantly, complete inhibition of canonical
hedgehog signalling was ineffective, indicating that the role of Gli1 both in
augmenting hedgehog signalling and in retarding myelination is specialized.
Indeed, inhibition of Gli1 improves the functional outcome in a
relapsing/remitting model of experimental autoimmune encephalomyelitis and is
neuroprotective. Thus, endogenous neural stem cells can be mobilized for the
repair of demyelinated lesions by inhibiting Gli1, identifying a new therapeutic
avenue for the treatment of demyelinating disorders.
PMID- 26416761
TI - Interplay between density and superconducting quantum critical fluctuations.
AB - We consider the case of a density-driven metal-superconductor transition in the
proximity of an electronic phase separation. In particular, we investigate the
interplay between superconducting fluctuations and density fluctuations, which
become quantum critical when the electronic phase separation vanishes at zero
temperature into a quantum critical point. In this situation, the critical
dynamical density fluctuations strongly affect the dynamics of the Cooper-pair
fluctuations, which acquire a more singular character with a z = 3 dynamical
critical index. This gives rise to a scenario that possibly rules the
disappearance of superconductivity when the electron density is reduced by
electrostatic gating at the LaAlO3/SrTiO3 interface.
PMID- 26416757
TI - A novel locus of resistance to severe malaria in a region of ancient balancing
selection.
AB - The high prevalence of sickle haemoglobin in Africa shows that malaria has been a
major force for human evolutionary selection, but surprisingly few other
polymorphisms have been proven to confer resistance to malaria in large
epidemiological studies. To address this problem, we conducted a multi-centre
genome-wide association study (GWAS) of life-threatening Plasmodium falciparum
infection (severe malaria) in over 11,000 African children, with replication data
in a further 14,000 individuals. Here we report a novel malaria resistance locus
close to a cluster of genes encoding glycophorins that are receptors for
erythrocyte invasion by P. falciparum. We identify a haplotype at this locus that
provides 33% protection against severe malaria (odds ratio = 0.67, 95% confidence
interval = 0.60-0.76, P value = 9.5 * 10(-11)) and is linked to polymorphisms
that have previously been shown to have features of ancient balancing selection,
on the basis of haplotype sharing between humans and chimpanzees. Taken together
with previous observations on the malaria-protective role of blood group O, these
data reveal that two of the strongest GWAS signals for severe malaria lie in or
close to genes encoding the glycosylated surface coat of the erythrocyte cell
membrane, both within regions of the genome where it appears that evolution has
maintained diversity for millions of years. These findings provide new insights
into the host-parasite interactions that are critical in determining the outcome
of malaria infection.
PMID- 26416762
TI - MC3T3-E1 Cells Behavior on Surfaces Bombarded by Argon Ions in Planar Cathode
Discharge.
AB - To evaluate the effect of topography in nanoscale, titanium surfaces were
bombarded by argon ions (a chemically inert gas), in an atmosphere of plasma. The
effects of surface parameters on morphology, adhesion, proliferation, and MC3T3
E1 preosteoblasts differentiation were analyzed. Nontreated (smooth) surfaces
were used as a control. The levels of average roughness (Ra) observed in
bombarded and smooth titanium surfaces were of 95 and 14 nm, respectively. The
wettability increased on treated surfaces. The number of attached cells (30 and
60 min) was significantly higher on the bombarded surface. The cell proliferation
after 3 and 7 days was also significantly higher on the ion-bombarded surface. In
addition, the ALP activity and expression of osteocalcin were higher in cells
grown on the treated surface. The results showed that bombardment with argon ions
increased the roughness and the wettability of the Ti surface, promoting a
significant increase in the adhesion, proliferation, and differentiation of
preosteoblasts.
PMID- 26416763
TI - The decrease in histone methyltransferase EZH2 in response to fluid shear stress
alters endothelial gene expression and promotes quiescence.
AB - High uniform fluid shear stress (FSS) is atheroprotective and preserves the
endothelial phenotype and function through activation of downstream mediators
such as MAPK7 (Erk5). Endothelial cells respond to FSS thanks to
mechanotransduction. However, how the resulting signaling is integrated and
resolved at the epigenetic level remains elusive. We hypothesized that Polycomb
methyltransferase EZH2 is involved in the effects of FSS in human endothelial
cells. We showed that FSS decreases the expression of the Polycomb
methyltransferase EZH2. Despite simultaneous activation of MAPK7, MAPK7 pathway
does not directly influence the transcription of EZH2. Interestingly though, the
knockdown of EZH2 activates the protective MAPK7 signaling in endothelial cells,
even in the absence of FSS. To understand the influence of the FSS-decreased
expression of EZH2 on endothelial transcriptome, we performed RNA-seq and
differential gene expression analysis. We identified candidate groups of genes
dependent on both EZH2 and FSS. Among those, Gene Ontology overrepresentation
analysis revealed highly significant enrichment of the cell cycle-related genes,
suggesting changes in proliferation. Indeed, the depletion of EZH2 strongly
inhibited endothelial proliferation, indicating cell cycle arrest. The
concomitant decrease in CCNA expression suggests the transition of endothelial
cells into a quiescent phenotype. Further bioinformatical analysis suggested
TXNIP as a possible mediator between EZH2 and cell cycle-related gene network.
Our data show that EZH2 is a FSS-responsive gene. Decreased EZH2 levels enhance
the activation of the atheroprotective MAPK7 signaling. Decrease in EZH2 under
FSS mediates the decrease in the expression of the network of cell cycle-related
genes, which allows the cells to enter quiescence. EZH2 is therefore important
for the protective effects of FSS in endothelium.
PMID- 26416766
TI - What Data Do States Collect Related to School Nurses, School Health, and the
Health Care Provided?
AB - School nurses collect data to report to their school district and state agencies.
However, there is no national requirement or standard to collect specific data,
and each state determines its own set of questions. This study resulted from a
joint resolution between the National Association of State School Nurse
Consultants and the National Association of School Nurses. The study sought to
determine whether similar data points were collected so that comparisons could be
made among states and to develop a framework to incorporate the data. Thirty-two
states provided their questionnaires or reports. There were 855 data points that
could be divided into data related to staff and to students. No categories were
measured by all states. The most common data points were the number of students,
health screenings, and the number of students with particular conditions for whom
the district provided services. A framework for data collection is proposed.
PMID- 26416764
TI - Causal mechanisms and balancing selection inferred from genetic associations with
polycystic ovary syndrome.
AB - Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in
women, yet there is little consensus regarding its aetiology. Here we perform a
genome-wide association study of PCOS in up to 5,184 self-reported cases of White
European ancestry and 82,759 controls, with follow-up in a further ~2,000
clinically validated cases and ~100,000 controls. We identify six signals for
PCOS at genome-wide statistical significance (P<5 * 10(-8)), in/near genes
ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four
epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4)
are associated with PCOS at or near genome-wide significance. Mendelian
randomization analyses indicate causal roles in PCOS aetiology for higher BMI
(P=2.5 * 10(-9)), higher insulin resistance (P=6 * 10(-4)) and lower serum sex
hormone binding globulin concentrations (P=5 * 10(-4)). Furthermore, genetic
susceptibility to later menopause is associated with higher PCOS risk (P=1.6 *
10(-8)) and PCOS-susceptibility alleles are associated with higher serum anti
Mullerian hormone concentrations in girls (P=8.9 * 10(-5)). This large-scale
study implicates an aetiological role of the epidermal growth factor receptors,
infers causal mechanisms relevant to clinical management and prevention, and
suggests balancing selection mechanisms involved in PCOS risk.
PMID- 26416765
TI - Comprehensive analysis of the flowering genes in Chinese cabbage and examination
of evolutionary pattern of CO-like genes in plant kingdom.
AB - In plants, flowering is the most important transition from vegetative to
reproductive growth. The flowering patterns of monocots and eudicots are
distinctly different, but few studies have described the evolutionary patterns of
the flowering genes in them. In this study, we analysed the evolutionary pattern,
duplication and expression level of these genes. The main results were as
follows: (i) characterization of flowering genes in monocots and eudicots,
including the identification of family-specific, orthologous and collinear genes;
(ii) full characterization of CONSTANS-like genes in Brassica rapa (BraCOL
genes), the key flowering genes; (iii) exploration of the evolution of COL genes
in plant kingdom and construction of the evolutionary pattern of COL genes; (iv)
comparative analysis of CO and FT genes between Brassicaceae and Grass, which
identified several family-specific amino acids, and revealed that CO and FT
protein structures were similar in B. rapa and Arabidopsis but different in rice;
and (v) expression analysis of photoperiod pathway-related genes in B. rapa under
different photoperiod treatments by RT-qPCR. This analysis will provide resources
for understanding the flowering mechanisms and evolutionary pattern of COL genes.
In addition, this genome-wide comparative study of COL genes may also provide
clues for evolution of other flowering genes.
PMID- 26416767
TI - Current Backpack Weight Status for Primary Schoolchildren in Colima, Mexico.
AB - The purpose of the study was to identify the current status of backpack weight in
primary schoolchildren in Colima, Mexico, in relation to gender, school grade
level, and body mass index. A cross-sectional study was conducted on 240 randomly
selected children from 20 primary schools. The participating children's parents
signed statements of informed consent. Descriptive statistics, the chi(2) test,
Student's t-test, and Kruskal-Wallis test were used. The mean age was 8.55 +/- 2
years (range: 5-12 years). Seventy-eight percent of the schoolchildren presented
with a backpack overload that was greater than 10% of their body weight. No
significant differences were found in relation to gender. Four out of every five
schoolchildren presented with backpack overload, exposing them to a potential
health problem. Education and public policy prevention strategies for this
situation should be implemented in Mexico and other regions of the world with the
same problem.
PMID- 26416768
TI - Quality improvement training for core medical and general practice trainees: a
pilot study of project participation, completion and journal publication.
AB - BACKGROUND AND OBJECTIVES: Small-scale quality improvement projects are expected
to make a significant contribution towards improving the quality of healthcare.
Enabling doctors-in-training to design and lead quality improvement projects is
important preparation for independent practice. Participation is mandatory in
speciality training curricula. However, provision of training and ongoing support
in quality improvement methods and practice is variable. We aimed to design and
deliver a quality improvement training package to core medical and general
practice specialty trainees and evaluate impact in terms of project
participation, completion and publication in a healthcare journal. METHOD: A
quality improvement training package was developed and delivered to core medical
trainees and general practice specialty trainees in the west of Scotland
encompassing a 1-day workshop and mentoring during completion of a quality
improvement project over 3 months. A mixed methods evaluation was undertaken and
data collected via questionnaire surveys, knowledge assessment, and formative
assessment of project proposals, completed quality improvement projects and
publication success. RESULTS: Twenty-three participants attended the training day
with 20 submitting a project proposal (87%). Ten completed quality improvement
projects (43%), eight were judged as satisfactory (35%), and four were submitted
and accepted for journal publication (17%). Knowledge and confidence in aspects
of quality improvement improved during the pilot, while early feedback on project
proposals was valued (85.7%). CONCLUSION: This small study reports modest success
in training core medical trainees and general practice specialty trainees in
quality improvement. Many gained knowledge of, confidence in and experience of
quality improvement, while journal publication was shown to be possible. The
development of educational resources to aid quality improvement project
completion and mentoring support is necessary if expectations for quality
improvement are to be realised.
PMID- 26416769
TI - Trends in Biotechnological Drugs for Cancer Treatment.
AB - BACKGROUND: Biotechnology, which promoted revolutions in many fields, generates
great expectations for the future, mainly in the pharmaceutical sector for the
treatment of several diseases. Cancer is a leading cause of death worldwide and
due to its complexity and singularity, there are a number of challenges that
limit the development of new drugs for antitumor therapies, making the research
for cancer treatment one of the most exploited in the medical field. OBJECTIVE:
The main objective of this article is to identify trends of biotechnological
advances that may have application in improving cancer therapies. METHOD:
Information from patent applications of biotechnological drugs in the last five
years was retrieved using Thomson Reuters Integrity database. RESULTS: Cancer is
the leading therapeutic condition found in patent documents. The subject matter
most cited in patent applications includes monoclonal antibodies, adoptive cell
therapy, RNA interference and new vaccine peptides. CONCLUSION: The analysis of
the documents has provided an overview of new biological alternatives for use in
cancer treatment, showing potential avenues for years to come.
PMID- 26416772
TI - Correction: Assessing dimerisation degree and cooperativity in a biomimetic small
molecule model by pulsed EPR.
AB - Correction for 'Assessing dimerisation degree and cooperativity in a biomimetic
small-molecule model by pulsed EPR' by K. Ackermann et al., Chem. Commun., 2015,
51, 5257-5260.
PMID- 26416770
TI - Changes in Frailty After Kidney Transplantation.
AB - OBJECTIVES: To understand the natural history of frailty after an aggressive
surgical intervention, kidney transplantation (KT). DESIGN: Prospective cohort
study (December 2008-March 2014). SETTING: Baltimore, Maryland. PARTICIPANTS:
Kidney transplantation recipients (N = 349). MEASUREMENTS: The Fried frailty
score was measured at the time of KT and during routine clinical follow-up. Using
a Cox proportional hazards model, factors associated with improvements in frailty
score after KT were identified. Using a longitudinal analysis, predictors of
frailty score changes after KT were identified using a multilevel mixed-effects
Poisson model. RESULTS: At KT, 19.8% of recipients were frail; 1 month after KT,
33.3% were frail; at 2 months, 27.7% were frail; and at 3 months, 17.2% were
frail. On average, frailty scores had worsened by 1 month (mean change 0.4, P <
.001), returned to baseline by 2 months (mean change 0.2, P = .07), and improved
by 3 months (mean change -0.3, P = .04) after KT. The only recipient or
transplant factor associated with improvement in frailty score after KT was pre
KT frailty (hazard ratio = 2.55, 95% confidence interval (CI) = 1.71-3.82, P <
.001). Pre-KT frailty status (relative risk (RR) = 1.49, 95% CI = 1.29-1.72, P <
.001), recipient diabetes mellitus (RR = 1.26, 95% CI = 1.08-1.46, P = .003), and
delayed graft function (RR = 1.22, 95% CI = 1.04-1.43, P = .02) were
independently associated with long-term changes in frailty score. CONCLUSION:
After KT, in adult recipients of all ages, frailty initially worsens but then
improves by 3 months. Although KT recipients who were frail at KT had higher
frailty scores over the long term, they were most likely to show improvements in
their physiological reserve after KT, supporting the transplantation in these
individuals and suggesting that pretransplant frailty is not an irreversible
state of low physiological reserve.
PMID- 26416773
TI - Indirect quantum sensors: improving the sensitivity in characterizing very weakly
coupled spins.
AB - We propose a scheme to increase the sensitivity and thus the detection volume of
nanoscale single molecule magnetic resonance imaging. The proposal aims to
surpass the T1 limited detection of the sensor by taking advantage of a long
lived ancillary nuclear spin to which the sensor is coupled. We show how this
nuclear spin takes over the role of the sensor spin, keeping the characteristic
time-scales of detection on the same order but with a longer life-time allowing
it to detect a larger volume of the sample, which is not possible by the sensor
alone.
PMID- 26416771
TI - Maternal bile acid transporter deficiency promotes neonatal demise.
AB - Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse neonatal
survival and is estimated to impact between 0.4 and 5% of pregnancies worldwide.
Here we show that maternal cholestasis (due to Abcb11 deficiency) produces
neonatal death among all offspring within 24 h of birth due to atelectasis
producing pulmonary hypoxia, which recapitulates the neonatal respiratory
distress of human ICP. Neonates of Abcb11-deficient mothers have elevated
pulmonary bile acids and altered pulmonary surfactant structure. Maternal absence
of Nr1i2 superimposed on Abcb11 deficiency strongly reduces maternal serum bile
acid concentrations and increases neonatal survival. We identify pulmonary bile
acids as a key factor in the disruption of the structure of pulmonary surfactant
in neonates of ICP. These findings have important implications for neonatal
respiratory failure, especially when maternal bile acids are elevated during
pregnancy, and highlight potential pathways and targets amenable to therapeutic
intervention to ameliorate this condition.
PMID- 26416774
TI - Neurosyphilis presenting as parkinsonism.
AB - In the postantibiotic era, neurosyphilis continues to have a significant
incidence, especially in certain subpopulations. We report, for the first time,
neurosyphilis presenting as parkinsonism without more typical neurosyphilitic
clinical features. A 53-year-old man developed clinical features of gradual onset
consistent with idiopathic Parkinson's disease but was found to have positive
treponemal serology and cerebrospinal fluid Venereal Disease Research Laboratory
(VRDL) reaction. Antibiotic treatment dramatically improved all the parkinsonian
symptoms. However, over the subsequent 15 years, the patient slowly deteriorated
again in a manner typical of idiopathic Parkinson's disease. A dopaminergic
deficit was demonstrated on ((123)I)FP-CIT SPECT. This is the first report in the
postantibiotic era of neurosyphilis presenting as relatively pure parkinsonism.
Blood test screening for syphilis is therefore appropriate if there is any
clinical doubt about an idiopathic parkinsonian presentation. The patient's late
second deterioration may suggest that the neurosyphilitic basal ganglial insult
primed or accelerated development of idiopathic-like disease.
PMID- 26416776
TI - Irreversible order-disorder transformation of Ge(0 0 1) probed by scanning
tunnelling microscopy.
AB - We investigate the surface structure of Ge(0 0 1) during the (2 * 1)-(1 * 1)
phase transition occurring at T > 1130 K by high-resolution scanning tunnelling
microscopy. We find a drastic size reduction of dimerized domains in line with
substantial dimer breakup accompanied by surface roughening. Completing the
picture provided by previous spectroscopic observations, probing with high
spatial resolution reveals the nucleation of several nanodomains with distinct
vicinal orientations and reconstructions. The structural transformation is
irreversible and is not observed for other singular faces of Ge.
PMID- 26416775
TI - Giant cell arteritis: a closer look at its ophthalmological manifestations.
AB - Giant cell arteritis with ocular involvement is an ocular emergency. Arteritic
anterior ischaemic optic neuropathy (AAION) is the most common ophthalmological
manifestation associated with this disease. Visual loss is usually permanent with
rare cases showing visual recovery. Visual improvement, if it occurs, is
generally limited, and the visual field defects are persistent and severe. The
main goal of AAION treatment is the preservation of vision in the fellow eye. In
patients with neurophthalmological manifestations, high-dose corticosteroids
should be initiated immediately and aggressively, and maintained thereafter. We
present a case of AAION and severe vision loss where significant visual recovery
was seen after treatment.
PMID- 26416777
TI - What are the best predictors for successful GnRH antagonist protocol in in vitro
fertilization (IVF) treatment?
AB - OBJECTIVE: To determine factors that affect the success rate of GnRH antagonist
protocol in in vitro fertilization (IVF) treatment. DESIGN: Retrospective cohort
study. PATIENTS: Patients who underwent IVF cycle with their first GnRH
antagonist protocol. INTERVENTION: Antagonist protocol during IVF treatment. The
main outcome measurements were; Number of retrieved oocytes, embryo quality and
pregnancy rate. RESULTS: Gravidity was negatively correlated with number of eggs
(p = 0.017), while total follicle number >=15 (p = 0.044) and E(2) on day of
human chorionic gonadotropin (HCG) (p = 0.000) had a positive correlation with
number of eggs. Maximum follicle size at HCG administration showed a trend toward
an inverse correlation (p = 0.053). Addition of LH to drug stimulation was
negatively correlated with number of eggs in comparison to rFSH only (p = 0.013
and 0.0000, respectively). Age and number of frozen eggs were negatively
correlated with successful pregnancy (p = 0.025 and 0.004, respectively), while
embryo quality, gravidity and number of embryos were positive (p = 0.011 and
0.014, respectively). CONCLUSION: Controlled parameters like timing of antagonist
start, duration of antagonist and the optimal leading follicle diameter for HCG
triggering had no effect on treatment outcomes.
PMID- 26416778
TI - Anti-Pseudomonas aeruginosa activity of 1,10-phenanthroline-based drugs against
both planktonic- and biofilm-growing cells.
AB - OBJECTIVES: The beneficial antimicrobial properties of 1,10-phenanthroline (phen)
based drugs, together with the imperative need to develop new chemotherapeutic
options for prevention/treatment of infections caused by MDR Gram-negative
bacteria, led us to evaluate the effects of phen, 1,10-phenanthroline-5,6-dione
(phendione), [Ag(phendione)2]ClO4 and [Cu(phendione)3](ClO4)2.4H2O on planktonic-
and biofilm-growing Pseudomonas aeruginosa. METHODS: Thirty-two non-duplicated
Brazilian clinical isolates of P. aeruginosa with distinct genetic backgrounds
were used in all experiments. The effect of test compounds on planktonic
bacterial proliferation was determined as recommended by CLSI protocol. The
effect on biofilm formation was evaluated by crystal violet incorporation
(biomass determination) and XTT (viability assay). Mature biofilm disorganization
was evidenced by staining with crystal violet. RESULTS: Phen-based compounds
presented anti-P. aeruginosa activity, but with different potencies concerning
the geometric mean MIC: [Cu(phendione)3](2+) (7.76 MUM) > [Ag(phendione)2](+)
(14.05 MUM) > phendione (31.15 MUM) > phen (579.28 MUM). MICs of each compound
were similar irrespective of whether the P. aeruginosa isolates were susceptible
or resistant to classical antimicrobials (ceftazidime, meropenem and imipenem).
The pretreatment of bacteria with phen, phendione and phendione's metal
derivatives at 0.5 * MIC value inhibited biofilm formation, particularly the use
of [Cu(phendione)3](2+) and [Ag(phendione)2](+), which significantly reduced both
biomass (48% and 44%, respectively) and viability (78% and 77%, respectively).
The compounds studied also disrupted mature biofilm in a dose-dependent manner,
especially [Ag(phendione)2](+) and [Cu(phendione)3](2+) (IC50, 9.39 and 10.16
MUM, respectively). CONCLUSIONS: Coordination of phendione to Ag(+) and Cu(2+)
represents a new promising group of anti-infective agents, which revealed a
potent anti-P. aeruginosa action against both planktonic- and biofilm-growing
cells.
PMID- 26416779
TI - A small Acinetobacter plasmid carrying the tet39 tetracycline resistance
determinant.
PMID- 26416780
TI - Population pharmacokinetics of meropenem administered as a prolonged infusion in
children with cystic fibrosis.
AB - OBJECTIVES: Meropenem is frequently used to treat pulmonary exacerbations in
children with cystic fibrosis (CF) in the USA. Prolonged-infusion meropenem
improves the time that free drug concentrations remain above the MIC (fT> MIC) in
adults, but data in CF children are sparse. We describe the population
pharmacokinetics, tolerability and treatment burden of prolonged-infusion
meropenem in CF children. METHODS: Thirty children aged 6-17 years with a
pulmonary exacerbation received 40 mg/kg meropenem every 8 h; each dose was
administered as a 3 h infusion. Pharmacokinetics were determined using population
methods in Pmetrics. Monte Carlo simulation was employed to compare 0.5 with 3 h
infusions to estimate the probability of pharmacodynamic target attainment (PTA)
at 40% fT> MIC. NCT#01429259. RESULTS: A two-compartment model fitted the data
best with clearance and volume predicted by body weight. Clearance and volume of
the central compartment were 0.41 +/- 0.23 L/h/kg and 0.30 +/- 0.17 L/kg,
respectively. Half-life was 1.11 +/- 0.38 h. At MICs of 1, 2 and 4 mg/L, PTAs for
the 0.5 h infusion were 87.6%, 70.1% and 35.4%, respectively. The prolonged
infusion increased PTAs to >99% for these MICs and achieved 82.8% at 8 mg/L. Of
the 30 children, 18 (60%) completed treatment with prolonged infusion; 5 did so
at home without any reported burden. Nine patients were changed to a 0.5 h
infusion when discharged home. CONCLUSIONS: In these CF children, meropenem
clearance was greater compared with published values from non-CF children.
Prolonged infusion provided an exposure benefit against pathogens with MICs >=1
mg/L, was well tolerated and was feasible to administer in the hospital and home
settings, the latter depending on perception and family schedule.
PMID- 26416781
TI - In vitro evaluation of dual carbapenem combinations against carbapenemase
producing Enterobacteriaceae.
AB - OBJECTIVES: This study aimed to analyse the in vitro activity of dual
combinations of carbapenems against Klebsiella pneumoniae producing the main
carbapenemase types. METHODS: MIC values of the carbapenems, imipenem, meropenem,
ertapenem and doripenem were determined alone and in dual combinations for 20
clinical K. pneumoniae isolates producing representative carbapenemases, i.e. OXA
48 (n = 6), NDM-1 (n = 4), NDM-1 + OXA-48 (n = 2) and KPC-2 (n = 8). MICs were
also determined for Escherichia coli recombinant strains with or without
permeability defects producing NDM-1, OXA-48 or KPC-2. In vitro synergy
combination testing was performed using the microdilution and chequerboard
techniques. Fractional inhibitory concentration indexes were calculated to
determine whether the combinations were synergistic, indifferent or antagonistic.
RESULTS: All carbapenemase producers were resistant to the tested carbapenems,
with most isolates showing MICs of carbapenems >32 mg/L. None of the combinations
was antagonistic. For KPC producers, synergistic combinations were observed with
imipenem/ertapenem (5/8 isolates), imipenem/doripenem (4/8), imipenem/doripenem
(4/8), meropenem/doripenem (3/8) and ertapenem/doripenem (3/8), while no synergy
was observed with meropenem/ertapenem. For OXA-48 producers, synergies were
observed with imipenem/ertapenem and with imipenem/meropenem for both isolates
tested. Notably, combining imipenem with a non-carbapenem beta-lactam (cefalotin)
did not give any synergistic result. No synergy was observed for all NDM-1 and
NDM-1+OXA-48 producers. Time-kill assays confirmed most of the data obtained by
chequerboard testing. CONCLUSIONS: The data strongly support the hypothesis that
dual carbapenem combinations might be effective against serine-beta-lactamase
producers (KPC, OXA-48). The imipenem-containing combinations appeared to be the
most efficient.
PMID- 26416782
TI - A Spanish Study on Psychological Predictors of Quality of Life in People with
HIV.
AB - In Spain little research has focused on assessment of health indicators, both
physical and psychological, in people living with HIV. The aim of this study is
to evaluate a set of different indicators that allow us to identify psychological
factors that may be influencing the quality of life of these people. The sample
consist of 744 people infected with HIV aged between from 18 to 82 years (M =
43.04; SD = 9.43). Results show that factors such as self-esteem and leading a
healthy lifestyle act as protectors in both, physical and mental health. On the
other hand, financial problems, body disfigurement, and depressive mood could
have harmful effects on both, physical and mental health. The structural model
reveals depressed mood as the factor with greatest influence upon mental health,
which in turn can be largely explained by factors such as the stress generated by
HIV and personal autonomy. This work has allowed us to identify the vulnerability
and protective factors that play a significant role in the physical and mental
HRQOL of persons with HIV, providing guidelines for design and implementation of
psychological intervention programs aimed to improve HRQOL in this population.
PMID- 26416783
TI - The role of seaweed bioactives in the control of digestion: implications for
obesity treatments.
AB - Seaweeds are an underutilised nutritional resource that could not only compliment
the current western diet but potentially bring additional health benefits over
and above their nutritional value. There are four groups of seaweed algae; green
algae (Chlorophyceae), red algae (Rhodophycae), blue-green algae (Cyanophyceae)
and brown algae (Phaeophyceae). Seaweeds are rich in bioactive components
including polysaccharides and polyphenols. Polysaccharides content, such as
fucoidan, laminarin, as well as alginate is generally high in brown seaweeds
which are also a source of polyphenols such as phenolic acids, flavonoids,
phlorotannin, stilbenes and lignans. These components have been shown to reduce
the activity of digestive enzymes, modulating enzymes such as alpha-amylase,
alpha-glucosidase, pepsin and lipase. This review discusses the effect of several
of these components on the digestive processes within the gastrointestinal tract;
focusing on the effect of alginate on pancreatic lipase activity and its
potential health benefits. Concluding that there is evidence to suggest alginate
has the potential to be used as an obesity treatment, however, further in vivo
research is required and an effective delivery method for alginate must be
designed.
PMID- 26416784
TI - One-year-old fear memories rapidly activate human fusiform gyrus.
AB - Fast threat detection is crucial for survival. In line with such evolutionary
pressure, threat-signaling fear-conditioned faces have been found to rapidly (<80
ms) activate visual brain regions including the fusiform gyrus on the
conditioning day. Whether remotely fear conditioned stimuli (CS) evoke similar
early processing enhancements is unknown. Here, 16 participants who underwent a
differential face fear-conditioning and extinction procedure on day 1 were
presented the initial CS 24 h after conditioning (Recent Recall Test) as well as
9-17 months later (Remote Recall Test) while EEG was recorded. Using a data
driven segmentation procedure of CS evoked event-related potentials, five
distinct microstates were identified for both the recent and the remote memory
test. To probe intracranial activity, EEG activity within each microstate was
localized using low resolution electromagnetic tomography analysis (LORETA). In
both the recent (41-55 and 150-191 ms) and remote (45-90 ms) recall tests, fear
conditioned faces potentiated rapid activation in proximity of fusiform gyrus,
even in participants unaware of the contingencies. These findings suggest that
rapid processing enhancements of conditioned faces persist over time.
PMID- 26416786
TI - Tools and pipelines for BioNano data: molecule assembly pipeline and FASTA super
scaffolding tool.
AB - BACKGROUND: Genome assembly remains an unsolved problem. Assembly projects face a
range of hurdles that confound assembly. Thus a variety of tools and approaches
are needed to improve draft genomes. RESULTS: We used a custom assembly workflow
to optimize consensus genome map assembly, resulting in an assembly equal to the
estimated length of the Tribolium castaneum genome and with an N50 of more than 1
Mb. We used this map for super scaffolding the T. castaneum sequence assembly,
more than tripling its N50 with the program Stitch. CONCLUSIONS: In this article
we present software that leverages consensus genome maps assembled from extremely
long single molecule maps to increase the contiguity of sequence assemblies. We
report the results of applying these tools to validate and improve a 7x Sanger
draft of the T. castaneum genome.
PMID- 26416785
TI - Escalating risk and the moderating effect of resistance to peer influence on the
P200 and feedback-related negativity.
AB - Young people frequently socialize together in contexts that encourage risky
decision making, pointing to a need for research into how susceptibility to peer
influence is related to individual differences in the neural processing of
decisions during sequentially escalating risk. We applied a novel analytic
approach to analyze EEG activity from college-going students while they completed
the Balloon Analogue Risk Task (BART), a well-established risk-taking propensity
assessment. By modeling outcome-processing-related changes in the P200 and
feedback-related negativity (FRN) sequentially within each BART trial as a
function of pump order as an index of increasing risk, our results suggest that
analyzing the BART in a progressive fashion may provide valuable new insights
into the temporal neurophysiological dynamics of risk taking. Our results showed
that a P200, localized to the left caudate nucleus, and an FRN, localized to the
left dACC, were positively correlated with the level of risk taking and reward.
Furthermore, consistent with our hypotheses, the rate of change in the FRN was
higher among college students with greater self-reported resistance to peer
influence.
PMID- 26416787
TI - Nocturnal enuresis: prevalence and risk factors among school-aged children with
sickle-cell anaemia in a South-east Nigerian city.
AB - BACKGROUND: Sickle-cell anaemia (SCA) is the most common inherited
haemoglobinopathy affecting the Negroid race. Renal complications such as
enuresis can occur during childhood. Reports show that children and adolescents
with SCA may be at a higher risk of nocturnal enuresis than their counterparts
with normal haemoglobin genotype. AIMS: The study aims to determine the
prevalence of nocturnal enuresis and possible risk factors among school-aged
children with SCA in a South-east Nigerian city. METHODS: A hospital-based and
cross-sectional descriptive study of 70 school-aged children with SCA who met the
study criteria, and 70 age- and sex-matched controls with normal haemoglobin
genotype was conducted in the Paediatric Sickle-cell Anaemia Clinic of the
University of Nigeria Teaching Hospital (UNTH) Enugu. Data was subjected to
multivariate analysis using logistic regression model with nocturnal enuresis as
the dependent variable and the possible risk factors as the independent
variables. RESULTS: The prevalence of nocturnal enuresis among the Subjects and
the Controls was 31.4 and 21.4 % respectively (p = 0.180). It was significantly
higher among male Subjects (48.7 %) than among male Controls (23.1 %) [OR (95 %
CI) =8.14 (2.12-31.24), p < 0.001]; and among Subjects whose parents had a
childhood history of enuresis [OR (95 %) =10.39 (2.45-44.05), p = 0.002]. The
difference in the prevalence of enuresis in the female cohort was however not
significant. CONCLUSIONS: Children with SCA have a tendency to develop nocturnal
enuresis when compared to their non-affected counterparts. Male gender and
parental childhood history of nocturnal enuresis are potential socio-demographic
risk factors.
PMID- 26416788
TI - Better prioritization to increase research value and decrease waste.
AB - In a recent study published in BMC Medicine, Singh Ospina and colleagues outlined
the important gaps between ongoing research and research needs in the field of
endocrinology. Many recommendations from clinical practice guidelines are based
on a low level of evidence, thereby resulting in research gaps. Despite the
publication of around 25,000 randomized controlled trials each year, ongoing
research does not cover most of these gaps. In contrast, trials are planned when
sufficient data are already available for decision making, which results in
redundant research and exposes patients to unnecessary risks. This lack of
prioritization contributes to the enormous problem of waste in research. A
systematic approach to accumulate the available body of evidence is necessary to
determine when we have sufficient evidence and when we have knowledge gaps,
defined as research questions with no or a low level of evidence available.
Systematic registration of research gaps and their prioritization may help to
organize future research. Some initiatives exist, but they need to be
generalized.Please see related research: http://www.biomedcentral.com/1741
7015/13/187.
PMID- 26416789
TI - The effect of a reversible shear transformation on plastic deformation of an
amorphous solid.
AB - Langevin dynamics simulations are performed to investigate the plastic response
of a model glass to a local shear transformation in a quiescent system. The
deformation of the material is induced by a spherical inclusion that is gradually
strained into an ellipsoid of the same volume and then reverted back into the
sphere. We show that the number of cage-breaking events increases with increasing
strain amplitude of the shear transformation. The results of numerical
simulations indicate that the density of cage jumps is larger in the cases of
weak damping or slow shear transformation. Remarkably, we also found that, for a
given strain amplitude, the peak value of the density profiles is a function of
the ratio of the damping coefficient and the time scale of the shear
transformation.
PMID- 26416790
TI - Advanced thyroid carcinoma in pregnancy: case report of two pregnancies.
AB - Differentiated thyroid carcinoma is one of the most frequently diagnosed cancers
during pregnancy, second only to breast cancer. Therefore, it would be of value
to determine if there are pregnancy-related physiological effects that impact
long-term prognosis for patients with this disease. Hormone effects attributable
to beta-human chorionic gonadotropin and estrogens seem particularly likely. We
present a case of a 40-year-old woman with thyroid follicular carcinoma with
accompanying bone metastases. The cancer was discovered immediately after
childbirth and the woman became pregnant again when the disease was in an
advanced stage. We describe the cancer evolution and present the maternal and
fetal results. Pregnancy in women with advanced thyroid carcinoma could affect
long-term prognosis. However, more studies are needed to evaluate this
hypothesis. In this unique case, there were two pregnancies and the second
occurred in an advanced state of the disease. We evaluated how these pregnancies
could affect short-term prognosis of the disease.
PMID- 26416791
TI - Predicting direct and indirect breeding values for survival time in laying hens
using repeated measures.
AB - BACKGROUND: Minimizing bird losses is important in the commercial layer industry.
Selection against mortality is challenging because heritability is low, censoring
is high, and individual survival depends on social interactions among cage
members. With cannibalism, mortality depends not only on an individual's own
genes (direct genetic effects; DGE) but also on genes of its cage mates (indirect
genetic effects; IGE). To date, studies using DGE-IGE models have focussed on
survival time but their shortcomings are that censored records were considered as
exact lengths of life and models assumed that IGE were continuously expressed by
all cage members even after death. However, since dead animals no longer express
IGE, IGE should ideally be time-dependent in the model. Neglecting censoring and
timing of IGE expression may reduce accuracy of estimated breeding values (EBV).
Thus, our aim was to improve prediction of breeding values for survival time in
layers that present cannibalism. METHODS: We considered four DGE-IGE models to
predict survival time in layers. One model was an analysis of survival time and
the three others treated survival in consecutive months as a repeated binomial
trait (repeated measures models). We also tested whether EBV were improved by
including timing of IGE expression in the analyses. Approximate EBV accuracies
were calculated by cross-validation. The models were fitted to survival data on
two purebred White Leghorn layer lines W1 and WB, each having monthly survival
records over 13 months. RESULTS: Including the timing of IGE expression in the
DGE-IGE model reduced EBV accuracy compared to analysing survival time. EBV
accuracy was higher when repeated measures models were used. However, there was
no universal best model. Using repeated measures instead of analysing survival
time increased EBV accuracy by 10 to 21 and 2 to 12 % for W1 and WB,
respectively. We showed how EBV and variance components estimated with repeated
measures models can be translated into survival time. CONCLUSIONS: Our results
suggest that prediction of breeding values for survival time in laying hens can
be improved using repeated measures models. This is an important result since
more accurate EBV contribute to higher rates of genetic gain.
PMID- 26416792
TI - A Large State Medicaid Outpatient Advanced Imaging Utilization Management
Program: Substantial Savings Without the Need for Denials.
AB - A decade of rapidly rising outpatient advanced imaging utilization ended toward
the end of the past decade, with slow growth since. This has been attributed to
repetitive reimbursement cuts, medical radiation exposure concerns, increasing
deductibles and patient copayments, and the influence of radiology benefit
management companies. State Medicaid programs have been reluctant to institute
radiology benefit management preauthorization programs since the time burden for
obtaining test approval could cause providers to drop out. Also, these patients
may lack the knowledge to appeal denials, and medically necessary tests could be
denied with adverse outcomes. Little data exist demonstrating the efficacy of
such programs in decreasing utilization and cost. We report a 2-year experience
with an outpatient advanced imaging prior notification program for a large state
Medicaid fee-for-service population. The program did not allow any denials, but
nevertheless the data reveal a large, durable decrease in advanced imaging
utilization and cost.
PMID- 26416793
TI - Editorial: From Multiple Hits to Multiple Therapeutic Targets of Non-Alcoholic
Fatty Liver Disease.
PMID- 26416794
TI - Evaluation of antioxidative and antitumor activities of extracted flavonoids from
Pink Lady apples in human colon and breast cancer cell lines.
AB - The antioxidative and anticancer effects of extracted flavonoids from Pink Lady
apples on human colon cancer LoVo cells and breast cancer MCF-7 cells were
evaluated. It was found that the antioxidative property of the peel-flavonoids
(Peel-F) was more effective than that of the flesh-flavonoids (Flesh-F).
Meanwhile, both the Peel-F and Flesh-F can inhibit cancer cell growth in a dose
dependent manner, with the IC50 values of 110.33 +/- 2.52 mg mL(-1) and 378.14 +/
1.64 mg mL(-1) for LoVo cells and 58.42 +/- 1.39 mg mL(-1) and 296.06 +/- 3.71
mg mL(-1) for MCF-7 cells. This led to the conclusion that the Peel-F were more
effective against cancer cells than the Flesh-F, and that the scavenging ROS
effects were significantly higher in the Peel-F in vitro. Moreover, we also found
that the generation of ROS is a critical mediator in apple flavonoid-induced cell
apoptosis and the induction effect of the Peel-F was significantly higher than
that of the Flesh-F.
PMID- 26416796
TI - In Memoriam: Charles M. Mansbach II (1937 - 2015).
PMID- 26416795
TI - Quantitative analysis of the murine lipid droplet-associated proteome during diet
induced hepatic steatosis.
AB - Hepatic steatosis is characterized by the accumulation of lipid droplets (LDs),
which are composed of a neutral lipid core surrounded by a phospholipid monolayer
embedded with many proteins. Although the LD-associated proteome has been
investigated in multiple tissues and organisms, the dynamic changes in the murine
LD-associated proteome in response to obesity and hepatic steatosis have not been
studied. We characterized the hepatic LD-associated proteome of C57BL/6J male
mouse livers following high-fat feeding using isobaric tagging for relative and
absolute quantification. Of the 1,520 proteins identified with a 5% local false
discovery rate, we report a total of 48 proteins that were increased and 52
proteins that were decreased on LDs in response to high-fat feeding. Most
notably, ribosomal and endoplasmic reticulum proteins were increased and
extracellular and cytosolic proteins were decreased in response to high-fat
feeding. Additionally, many proteins involved in fatty acid catabolism or
xenobiotic metabolism were enriched in the LD fraction following high-fat
feeding. In contrast, proteins involved in glucose metabolism and liver X
receptor or retinoid X receptor activation were decreased on LDs of high-fat-fed
mice. This study provides insights into unique biological functions of hepatic
LDs under normal and steatotic conditions.
PMID- 26416797
TI - Preparation of intravenous cholesterol tracer using current good manufacturing
practices.
AB - Studies of human reverse cholesterol transport require intravenous infusion of
cholesterol tracers. Because insoluble lipids may pose risk and because it is
desirable to have consistent doses of defined composition available over many
months, we investigated the manufacture of cholesterol tracer under current good
manufacturing practice (CGMP) conditions appropriate for phase 1 investigation.
Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or
cholesterol-d7 in ethanol with 20% Intralipid((r)). The resulting material was
filtered through a 1.2 micron particulate filter, stored at 4 degrees C, and
tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity,
autoxidation, and particle size and aggregation. The limiting factor for
stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over
9 months (P < 0.01). The emulsion was stable with the Z-average intensity
weighted mean droplet diameter remaining at 60 nm over 23 months. The zeta
potential (a measure of negative surface charge protecting from aggregation) was
unchanged at -36.2. Rapid cholesterol pool size was 25.3 +/- 1.3 g. Intravenous
cholesterol tracer was stable at 4 degrees C for 9 months postproduction. CGMP
manufacturing methods can be achieved in the academic setting and need to be
considered for critical components of future metabolic studies.
PMID- 26416798
TI - Takotsubo cardiomyopathy in myasthaenia gravis crisis confirmed by cardiac MRI.
AB - Myasthaenia gravis crisis and Takotsubo cardiomyopathy are rare conditions that
can be precipitated by emotional or physical stress. Myasthaenia gravis has a
variety of cardiac manifestations but Takotsubo cardiomyopathy, particularly in
male patients, has rarely been reported. We describe a unique case of a 70-year
old man who developed Takotsubo cardiomyopathy during his first presentation with
a myasthaenia gravis crisis. He had not received plasmapharesis or immunoglobulin
therapy. Striking ECG traces and cardiac MRI helped to confirm the diagnosis.
Cardiac manifestations of myasthaenia gravis and myasthaenia gravis itself have
overlapping symptoms; the importance of cardiac monitoring and clinical vigilance
in such cases is discussed. The utility of cardiac MRI in assessing cardiac
manifestations of myasthaenia gravis is also highlighted.
PMID- 26416799
TI - Association between intrauterine mild hyperglycemia and post-natal high-fat diet
with adiponectin and AMPK pathway genes.
AB - To investigate the mechanisms of maternal-fetal interactions in the setting of
gestational diabetes mellitus. We investigated the long-term effects of
intrauterine mild hyperglycemia and a postnatal high-fat diet on the glucose
metabolism of adult offspring, and explored the role of adiponectin on hepatic
gluconeogenesis. Twenty-one pregnant Wistar rats were randomly divided into an
intrauterine hyperglycemia group (group D, n = 14) and a control group (group C,
n = 7). Offspring were divided into four groups according to intrauterine blood
glucose level and post-weaning dietary patterns (high-fat diet groups: DF and CF
or normal diet groups: DN and CN, n = 8 per group). The average birth weights of
group D offspring were higher than for group C. In the DF rats, low adiponectin
mRNA expression in perirenal and epididymal fat was significantly positively
correlated with low hepatic AdipoR1 mRNA expression and significantly correlated
with high hepatic PEPCK, G-6-Pase, and PGC-1alpha mRNA levels. In DF rats,
hepatic P-AMPK was cytoplasmically located and its level was decreased; in these
rats, hepatic CRTC2 was expressed in the nucleus and its level was significantly
increased. Our study shows that the dietary structure of offspring has a large
influence on the incidence of abnormal glucose tolerance.
PMID- 26416800
TI - Memory and Mechanism.
PMID- 26416801
TI - Cystic lesion of the fourth ventricle: Role of CISS.
PMID- 26416802
TI - Metastatic breast cancer in a man with nonprogressive ataxia and epilepsy.
PMID- 26416803
TI - Association of prone position with sudden unexpected death in epilepsy.
PMID- 26416804
TI - Mindfulness therapy and seizures.
PMID- 26416805
TI - Mystery Case: Intracranial hemorrhage in adult vein of Galen malformation.
PMID- 26416806
TI - Clinical Reasoning: A 73-year-old man with diplopia and ataxia.
PMID- 26416807
TI - Escherichia coli O157:H7 strains harbor at least three distinct sequence types of
Shiga toxin 2a-converting phages.
AB - BACKGROUND: Shiga toxin-producing Escherichia coli O157:H7 is a foodborne
pathogen that causes severe human diseases including hemolytic uremic syndrome
(HUS). The virulence factor that mediates HUS, Shiga toxin (Stx), is encoded
within the genome of a lambdoid prophage. Although draft sequences are publicly
available for a large number of E. coli O157:H7 strains, the high sequence
similarity of stx-converting bacteriophages with other lambdoid prophages poses
challenges to accurately assess the organization and plasticity among stx
converting phages due to assembly difficulties. METHODS: To further explore
genome plasticity of stx-converting prophages, we enriched phage DNA from 45
ciprofloxacin-induced cultures for subsequent 454 pyrosequencing to facilitate
assembly of the complete phage genomes. In total, 22 stx2a-converting phage
genomes were closed. RESULTS: Comparison of the genomes distinguished nine
distinct phage sequence types (PSTs) delineated by variation in obtained
sequences, such as single nucleotide polymorphisms (SNPs) and insertion sequence
element prevalence and location. These nine PSTs formed three distinct clusters,
designated as PST1, PST2 and PST3. The PST2 cluster, identified in two clade 8
strains, was related to stx2a-converting phages previously identified in non-O157
Shiga-toxin producing E. coli (STEC) strains associated with a high incidence of
HUS. The PST1 cluster contained phages related to those from E. coli O157:H7
strain Sakai (lineage I, clade 1), and PST3 contained a single phage that was
distinct from the rest but most related to the phage from E. coli O157:H7 strain
EC4115 (lineage I/II, clade 8). Five strains carried identical stx2a-converting
phages (PST1-1) integrated at the same chromosomal locus, but these strains
produced different levels of Stx2. CONCLUSION: The stx2a-converting phages of E.
coli O157:H7 can be categorized into at least three phage types. Diversification
within a phage type is mainly driven by IS629 and by a small number of SNPs.
Polymorphisms between phage genomes may help explain differences in Stx2a
production between strains, however our data indicates that genes encoded
external to the phage affect toxin production as well.
PMID- 26416808
TI - Objectively Measured Sedentary Time and Cardiometabolic Biomarkers in US
Hispanic/Latino Adults: The Hispanic Community Health Study/Study of Latinos
(HCHS/SOL).
AB - BACKGROUND: Sedentary behavior is recognized as a distinct construct from lack of
moderate-vigorous physical activity and is associated with deleterious health
outcomes. Previous studies have primarily relied on self-reported data, whereas
data on the relationship between objectively measured sedentary time and
cardiometabolic biomarkers are sparse, especially among US Hispanics/Latinos.
METHODS AND RESULTS: We examined associations of objectively measured sedentary
time (via Actical accelerometers for 7 days) and multiple cardiometabolic
biomarkers among 12 083 participants, aged 18 to 74 years, from the Hispanic
Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos of diverse
backgrounds (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South
American) were recruited from 4 US cities between 2008 and 2011. Sedentary time
(<100 counts/min) was standardized to 16 hours/d of wear time. The mean sedentary
time was 11.9 hours/d (74% of accelerometer wear time). After adjustment for
moderate-vigorous physical activity and confounding variables, prolonged
sedentary time was associated with decreased high-density lipoprotein cholesterol
(P=0.04), and increased triglycerides, 2-hour glucose, fasting insulin, and
homeostatic model assessment of insulin resistance (all P<0.0001). These
associations were generally consistent across age, sex, Hispanic/Latino
backgrounds, and physical activity levels. Even among individuals meeting
physical activity guidelines, sedentary time was detrimentally associated with
several cardiometabolic biomarkers (diastolic blood pressure, high-density
lipoprotein cholesterol, fasting and 2-hour glucose, fasting insulin and
homeostatic model assessment of insulin resistance; all P<0.05). CONCLUSIONS: Our
large population-based, objectively derived data showed deleterious associations
between sedentary time and cardiometabolic biomarkers, independent of physical
activity, in US Hispanics/Latinos. Our findings emphasize the importance of
reducing sedentary behavior for the prevention of cardiometabolic diseases, even
in those who meet physical activity recommendations.
PMID- 26416809
TI - Vascular Smooth Muscle Cell Senescence Promotes Atherosclerosis and Features of
Plaque Vulnerability.
AB - BACKGROUND: Although vascular smooth muscle cell (VSMC) proliferation is
implicated in atherogenesis, VSMCs in advanced plaques and cultured from plaques
show evidence of VSMC senescence and DNA damage. In particular, plaque VSMCs show
shortening of telomeres, which can directly induce senescence. Senescence can
have multiple effects on plaque development and morphology; however, the
consequences of VSMC senescence or the mechanisms underlying VSMC senescence in
atherosclerosis are mostly unknown. METHODS AND RESULTS: We examined the
expression of proteins that protect telomeres in VSMCs derived from human plaques
and normal vessels. Plaque VSMCs showed reduced expression and telomere binding
of telomeric repeat-binding factor-2 (TRF2), associated with increased DNA
damage. TRF2 expression was regulated by p53-dependent degradation of the TRF2
protein. To examine the functional consequences of loss of TRF2, we expressed
TRF2 or a TRF2 functional mutant (T188A) as either gain- or loss-of-function
studies in vitro and in apolipoprotein E(-/-) mice. TRF2 overexpression bypassed
senescence, reduced DNA damage, and accelerated DNA repair, whereas TRF2(188A)
showed opposite effects. Transgenic mice expressing VSMC-specific TRF2(T188A)
showed increased atherosclerosis and necrotic core formation in vivo, whereas
VSMC-specific TRF2 increased the relative fibrous cap and decreased necrotic core
areas. TRF2 protected against atherosclerosis independent of secretion of
senescence-associated cytokines. CONCLUSIONS: We conclude that plaque VSMC
senescence in atherosclerosis is associated with loss of TRF2. VSMC senes cence
promotes both atherosclerosis and features of plaque vulnerability, identifying
prevention of senescence as a potential target for intervention.
PMID- 26416811
TI - Postpartum Hypertension: "It Ain't Over 'til It's Over".
PMID- 26416810
TI - Epidemiology and Mechanisms of De Novo and Persistent Hypertension in the
Postpartum Period.
AB - BACKGROUND: The pathophysiology of hypertension in the immediate postpartum
period is unclear. METHODS AND RESULTS: We studied 988 consecutive women admitted
to a tertiary medical center for cesarean section of a singleton pregnancy. The
angiogenic factors soluble fms-like tyrosine kinase 1 and placental growth
factor, both biomarkers associated with preeclampsia, were measured on antepartum
blood samples. We then performed multivariable analyses to determine factors
associated with the risk of developing postpartum hypertension. Of the 988 women,
184 women (18.6%) developed postpartum hypertension. Of the 184 women, 77
developed de novo hypertension in the postpartum period, and the remainder had a
hypertensive disorder of pregnancy in the antepartum period. A higher body mass
index and history of diabetes mellitus were associated with the development of
postpartum hypertension. The antepartum ratio of soluble fms-like tyrosine kinase
1 to placental growth factor positively correlated with blood pressures in the
postpartum period (highest postpartum systolic blood pressure [r=0.29, P<0.001]
and diastolic blood pressure [r=0.28, P<0.001]). Moreover, the highest tertile of
the antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth
factor was independently associated with postpartum hypertension (de novo
hypertensive group: odds ratio, 2.25; 95% confidence interval, 1.19-4.25; P=0.01;
in the persistent hypertensive group: odds ratio, 2.61; 95% confidence interval,
1.12-6.05; P=0.02) in multivariable analysis. Women developing postpartum
hypertension had longer hospitalizations than those who remained normotensive
(6.5+/-3.5 versus 5.7+/-3.4 days; P<0.001). CONCLUSIONS: Hypertension in the
postpartum period is relatively common and is associated with prolonged
hospitalization. Women with postpartum hypertension have clinical risk factors
and an antepartum plasma angiogenic profile similar to those found in women with
preeclampsia. These data suggest that women with postpartum hypertension may
represent a group of women with subclinical or unresolved preeclampsia.
PMID- 26416812
TI - Magnetic nanoparticle-mediated hyperthermia therapy induces tumour growth
inhibition by apoptosis and Hsp90/AKT modulation.
AB - PURPOSE: We have evaluated the hyperthermia efficacy of oleic acid-functionalised
Fe(3)O(4) magnetic nanoparticles (MN-OA) under in vivo conditions and elucidated
the underlying mechanism of tumour growth inhibition. MATERIALS AND METHODS: The
efficacy and mechanism of tumour growth inhibition by MN-OA-mediated magnetic
hyperthermia therapy (MHT) was evaluated in a murine fibrosarcoma tumour model
(WEHI-164) using techniques such as TUNEL assay, Western blotting (WB),
immunofluorescence (IF) staining and histopathological examination. In addition,
bio-distribution of MN-OA in tumour/other target organs and its effect on normal
organ function were studied by Prussian blue staining and serum biochemical
analysis, respectively. RESULTS: MN-OA-induced MHT resulted in significant
inhibition of tumour growth as determined by measurement of tumour volume, as
well as by in vivo imaging of tumour derived from luciferase-transfected WEHI-164
cells. Histopathology analysis showed presence of severe apoptosis and reduced
tumour cells proliferation, which was further confirmed by TUNEL assay, reduced
expression of Ki-67 and enhanced level of cleaved caspase-3, in tumours treated
with MHT. Moreover, expression of heat stress marker, Hsp90 and its client
protein, AKT/PKB was reduced by ~50 and 80%, respectively, in tumours treated
with MHT as studied by WB and IF staining. Serum analysis suggested insignificant
toxicity of MN-OA (in terms of liver and kidney function), which was further
correlated with minimal accumulation of MN-OA in target organs. CONCLUSIONS:
These results suggest the involvement of apoptosis and Hsp90/AKT modulation in MN
OA-mediated MHT-induced tumour growth inhibition.
PMID- 26416813
TI - High-level adherence to a Mediterranean diet beneficially impacts the gut
microbiota and associated metabolome.
AB - OBJECTIVES: Habitual diet plays a major role in shaping the composition of the
gut microbiota, and also determines the repertoire of microbial metabolites that
can influence the host. The typical Western diet corresponds to that of an
omnivore; however, the Mediterranean diet (MD), common in the Western
Mediterranean culture, is to date a nutritionally recommended dietary pattern
that includes high-level consumption of cereals, fruit, vegetables and legumes.
To investigate the potential benefits of the MD in this cross-sectional survey,
we assessed the gut microbiota and metabolome in a cohort of Italian individuals
in relation to their habitual diets. DESIGN AND RESULTS: We retrieved daily
dietary information and assessed gut microbiota and metabolome in 153 individuals
habitually following omnivore, vegetarian or vegan diets. The majority of vegan
and vegetarian subjects and 30% of omnivore subjects had a high adherence to the
MD. We were able to stratify individuals according to both diet type and
adherence to the MD on the basis of their dietary patterns and associated
microbiota. We detected significant associations between consumption of vegetable
based diets and increased levels of faecal short-chain fatty acids, Prevotella
and some fibre-degrading Firmicutes, whose role in human gut warrants further
research. Conversely, we detected higher urinary trimethylamine oxide levels in
individuals with lower adherence to the MD. CONCLUSIONS: High-level consumption
of plant foodstuffs consistent with an MD is associated with beneficial
microbiome-related metabolomic profiles in subjects ostensibly consuming a
Western diet. TRIAL REGISTRATION NUMBER: This study was registered at clinical
trials.gov as NCT02118857.
PMID- 26416814
TI - Inspecting the Mechanism: A Longitudinal Analysis of Socioeconomic Status
Differences in Perceived Influenza Risks, Vaccination Intentions, and Vaccination
Behaviors during the 2009-2010 Influenza Pandemic.
AB - BACKGROUND: Influenza vaccination is strongly associated with socioeconomic
status, but there is only limited evidence on the respective roles of
socioeconomic differences in vaccination intentions versus corresponding
differences in follow-through on initial vaccination plans for subsequent
socioeconomic differences in vaccine uptake. METHODS: Nonparametric mean
smoothing, linear regression, and probit models were used to analyze longitudinal
survey data on perceived influenza risks, behavioral vaccination intentions, and
vaccination behavior of adults during the 2009-2010 influenza A/H1N1 ("swine
flu") pandemic in the United States. Perceived influenza risks and behavioral
vaccination intentions were elicited prior to the availability of H1N1 vaccine
using a probability scale question format. H1N1 vaccine uptake was assessed at
the end of the pandemic. RESULTS: Education, income, and health insurance
coverage displayed positive associations with behavioral intentions to get
vaccinated for pandemic influenza while employment was negatively associated with
stated H1N1 vaccination intentions. Education and health insurance coverage also
displayed significant positive associations with pandemic vaccine uptake.
Moreover, behavioral vaccination intentions showed a strong and statistically
significant positive partial association with later H1N1 vaccination.
Incorporating vaccination intentions in a statistical model for H1N1 vaccine
uptake further highlighted higher levels of follow-through on initial vaccination
plans among persons with higher education levels and health insurance.
LIMITATIONS: Sampling bias, misreporting in self-reported data, and limited
generalizability to nonpandemic influenza are potential limitations of the
analysis. CONCLUSIONS: Closing the socioeconomic gap in influenza vaccination
requires multipronged strategies that not only increase vaccination intentions by
improving knowledge, attitudes, and beliefs but also facilitate follow-through on
initial vaccination plans by improving behavioral control and access to
vaccination for individuals with low education, employed persons, and the
uninsured.
PMID- 26416815
TI - Proteomic changes of the porcine small intestine in response to chronic heat
stress.
AB - Acute heat stress (HS) negatively affects intestinal integrity and barrier
function. In contrast, chronic mild HS poses a distinct challenge to animals.
Therefore, this study integrates biochemical, histological and proteomic
approaches to investigate the effects of chronic HS on the intestine in finishing
pigs. Castrated male crossbreeds (79.00 +/- 1.50 kg BW) were subjected to either
thermal neutral (TN, 21 degrees C; 55% +/- 5% humidity; n=8) or HS conditions
(30 degrees C; 55% +/- 5% humidity; n=8) for 3 weeks. The pigs were sacrificed
after 3 weeks of high environmental exposure and the plasma hormones, the
intestinal morphology, integrity, and protein profiles of the jejunum mucosa were
determined. Chronic HS reduced the free triiodothyronine (FT3) and GH levels. HS
damaged intestinal morphology, increased plasma d-lactate concentrations and
decreased alkaline phosphatase activity of intestinal mucosa. Proteome analysis
of the jejunum mucosa was conducted by 2D gel electrophoresis and mass
spectrometry. Fifty-three intestinal proteins were found to be differentially
abundant, 18 of which were related to cell structure and motility, and their
changes in abundance could comprise intestinal integrity and function. The down
regulation of proteins involved in tricarboxylic acid cycle (TCA cycle), electron
transport chain (ETC), and oxidative phosphorylation suggested that chronic HS
impaired energy metabolism and thus induced oxidative stress. Moreover, the
changes of ten proteins in abundance related to stress response and defense
indicated pigs mediated long-term heat exposure and counteracted its negative
effects of heat exposure. These findings have important implications for
understanding the effect of chronic HS on intestines.
PMID- 26416816
TI - Abnormal Patella Height Based on Insall-Salvati Ratio and its Correlation with
Patellar Cartilage Lesions: An Extremity-Dedicated Low-Field Magnetic Resonance
Imaging Analysis of 1703 Chinese Cases.
AB - BACKGROUND AND AIMS: Diagnostic performance of patellar position for patellar
cartilage lesions remains unclear. The aim of this study was to assess the
abnormal patella height and its correlation with chondral lesions of the
patellofemoral joint in China. MATERIAL AND METHODS: A total of 1703 consecutive
patients who performed knee joint examination using an extremity-dedicated low
field magnetic resonance imaging were enrolled in this study. Patellar cartilage
lesions were diagnosed based on the result of magnetic resonance imaging and
clinical data. Patella height was defined as the ratio of patellar tendon length
to patellar length according to Insall-Salvati index. Patella alta and infera
were defined as tendon length/patellar length >1.2 and <0.8, respectively.
RESULTS: The total prevalence of patellar cartilage lesions was 38.0%. The
prevalence in females was significantly higher than that in males (46.4% vs
28.8%, p < 0.001). Age notably increased the incidence of patellar cartilage
lesions (p < 0.001). Logistic regression analysis showed that tendon
length/patellar length ratio was significantly correlated with patellar cartilage
lesions (odds ratio = 6.380, p < 0.001). Furthermore, patients with cartilage
lesions showed significantly higher rates of patella alta and infera (p < 0.001).
In addition, receiver operating characteristic curve analysis demonstrated that
abnormal patella height had statistical significance in diagnosing cartilage
lesions (p < 0.001). However, the area under the curve (0.596; 95% confidence
interval: 0.568-0.624) and sensitivity (47.0%) were relatively low, while the
specificity was 72.2%. CONCLUSIONS: Patients with patellar cartilage lesions have
an increased tendon length/patellar length ratio. The abnormal patella height is
significantly correlated with chondral lesions and can be used as a potential
diagnostic marker.
PMID- 26416817
TI - A rare case of racemose neurocysticercosis and its complications. Case report.
AB - Neurocysticercosis is a central nervous system infection caused by the pork
tapeworm Taenia solium. The disease is endemic in Central and South America, Asia
and Africa. Racemose neurocysticercosis refers to cysts in the subarachnoid space
and is characterized by proliferative lobulated cysts without a scolex. We report
a case of a 43-year-old woman with an eight-month history of headaches, ataxia
and loss of vision. CT and MRI showed an intraventricular cyst, causing
entrapment of Monro foramina and hydrocephalus, smaller cysts at subarachnoid
space in temporal lobes, Sylvian fissures, supra-selar and perimesencephalic
cisterns, and an intra-orbital cyst. Additionally, there were acute ischemic
vascular lesions on the left thalamus and corpus callosum splenium and subacute
ischemic lesions of both occipital lobes. The diagnosis of racemose cysticercosis
was made after biopsy and drainage of the intraventricular cyst. It is important
to recognize neurocysticercosis as a differential diagnosis in intra-cranial
cysts, not only intraparenchymal cysts.
PMID- 26416818
TI - Labelling and imaging of single endogenous messenger RNA particles in vivo.
AB - RNA molecules carry out widely diverse functions in numerous different
physiological processes in living cells. The RNA life cycle from transcription,
through the processing of nascent RNA, to the regulatory function of non-coding
RNA and cytoplasmic translation of messenger RNA has been studied extensively
using biochemical and molecular biology techniques. In this Commentary, we
highlight how single molecule imaging and particle tracking can yield further
insight into the dynamics of RNA particles in living cells. In the past few
years, a variety of bright and photo-stable labelling techniques have been
developed to generate sufficient contrast for imaging of single endogenous RNAs
in vivo. New imaging modalities allow determination of not only lateral but also
axial positions with high precision within the cellular context, and across a
wide range of specimen from yeast and bacteria to cultured cells, and even
multicellular organisms or live animals. A whole range of methods to locate and
track single particles, and to analyze trajectory data are available to yield
detailed information about the kinetics of all parts of the RNA life cycle.
Although the concepts presented are applicable to all types of RNA, we showcase
here the wealth of information gained from in vivo imaging of single particles by
discussing studies investigating dynamics of intranuclear trafficking, nuclear
pore transport and cytoplasmic transport of endogenous messenger RNA.
PMID- 26416819
TI - Diabetes and Aortic Aneurysm.
PMID- 26416820
TI - Liver Function is Associated With Response to Clopidogrel Therapy in Patients
Undergoing Angioplasty and Stenting.
AB - The relationship between liver function and clopidogrel response has not been
studied so far. We therefore sought to investigate the associations between 3
parameters of liver synthesis and on-treatment platelet reactivity to adenosine
diphosphate in patients on dual antiplatelet therapy. On-treatment platelet
reactivity was determined by the VerifyNow P2Y12 assay in 316 patients undergoing
angioplasty with stent implantation for cardiovascular disease. Cholinesterase,
serum albumin, and total cholesterol levels were measured by internationally
standardized assays in the hospital's central laboratory. On-treatment platelet
reactivity by the VerifyNow P2Y12 assay correlated inversely with cholinesterase,
serum albumin, and total cholesterol levels (all P <= .02). The inverse
associations of cholinesterase and serum albumin levels with platelet reactivity
remained significant after adjustment for cytochrome P450 loss-of-function
polymorphisms and other factors that were previously associated with high on
treatment residual platelet reactivity (HRPR; both P < .05). Patients without
HRPR by the VerifyNow P2Y12 assay had significantly higher levels of serum
albumin and total cholesterol than patients with HRPR (both P = .008). In
conclusion, liver function is associated with response to clopidogrel therapy in
patients undergoing angioplasty and stenting for cardiovascular disease.
PMID- 26416824
TI - Engaging Parents Who Quit Smoking in Antismoking Socialization of Children: A
Novel Approach to Relapse Prevention.
AB - INTRODUCTION: Data from a randomized controlled trial designed primarily to test
the effect of an antismoking socialization parenting program on child initiation
of smoking were used to test the subsidiary hypothesis that providing antismoking
socialization to children would lower the odds of relapse within a sub-sample of
parents who had recently quit smoking. METHODS: Over 13 months, 11 state
Quitlines provided contact information for callers who were parents of 8- to 10
year-old children. Of 1604 parents enrolled in the trial, 689 (344 treatment; 345
control) had quit smoking cigarettes for at least 24 hours after calling a
Quitline. Their data were used to test for group differences in 30-day abstinence
measured using telephone interviews conducted 7 and 12 months post-baseline.
Analyses of parents with complete follow-up data and intent-to-treat analyses
incorporating parents lost to follow-up are presented. RESULTS: Among 465 parents
with complete follow-up data, treatment group parents had twice the odds of being
abstinent 12 months post-baseline (adjusted OR = 2.01; P = .001) relative to
controls. Intent-to-treat analysis with all 689 parents, in which those lost to
follow-up were coded as having relapsed, showed a smaller though significant
treatment effect on 30-day abstinence at 12 months (adjusted OR = 1.58; P =
.017). CONCLUSIONS: This study is the first to observe that engaging parents who
have quit smoking in antismoking socialization of children can lower their odds
of relapse. Additional research is needed to replicate this finding and to
identify the psychological mechanisms underlying the observed effect.
IMPLICATIONS: There is a clear the need for research to develop new relapse
prevention strategies. This study is the first to observe that engaging parents
who have quit smoking in antismoking socialization of children can lower their
odds of relapse.
PMID- 26416823
TI - E-Cigarettes and the Drug Use Patterns of Adolescents.
AB - INTRODUCTION: This study examines the role of e-cigarettes in the drug use
patterns of adolescents. Of specific interest is whether adolescent e-cigarette
users fall into a group of (1) youth who do not use traditional drugs of abuse or
(2) polysubstance users. METHODS: Using latent class analysis, we identify major
"classes" of substance users on the basis of recent use of e-cigarettes, alcohol,
marijuana, cigarettes, and prescription drugs. Analyses are conducted separately
for adolescents in 8th, 10th, and 12th grades. Data come from 16 615 participants
in the 2014 Monitoring the Future survey. RESULTS: Youth who do not use
traditional drugs of abuse account for about 50% of e-cigarette users in 8th
grade, 35% in 10th grade, and 17% in 12th grade. These youth come from a large
"low-level users" group found in each grade, characterized by low probability of
use for all substances (e-cigarette probability in this group for 8th graders =
.046; 10th graders = .071; 12th graders = .027). Other e-cigarette users come
from a smaller, "poly-users" group found in each grade, characterized by high-to
moderate probabilities (.83-.21) of using e-cigarettes and other substances.
Specific to 12th grade is a third, additional polysubstance group characterized
by high likelihood of e-cigarette use (.93). CONCLUSIONS: The proportion of e
cigarette users who do not use traditional drugs of abuse is larger at younger
ages. Longitudinal panel studies starting at 8th and 10th grades may best inform
the current debate on whether e-cigarette use is a risk or protective factor for
future transition to the use of other substances. IMPLICATIONS: The proportion of
e-cigarette users who do not use traditional drugs of abuse is larger at younger
ages. Longitudinal panel studies starting at 8th and 10th grades may best inform
the current debate on whether e-cigarette use is a risk or protective factor for
future transition to the use of other substances.
PMID- 26416825
TI - Genetic Risk Determinants for Cigarette Smoking Dependence in Mexican Mestizo
Families.
AB - INTRODUCTION: Tobacco smoking is a leading cause of mortality in developed and
developing countries. Despite antitobacco and smoke-free policies, the prevalence
of active smokers in Mexican urban populations has remained stable. Mexican
smokers differ from Caucasian and other ethnic groups, probably due to
sociocultural and genetic background characteristics. This study explored the
effect of known genetic variants on smoking behavior in Mexico City residents.
METHODS: Three hundred sixty-four Mexican Mestizo Mexico City residents from 87
families with at least one smoker were assessed for association of 12 gene
variants of six candidate genes (CHRNA4, CHRNB2, DRD2, ANKK1, SLC6A3, and CYP2A6)
with cigarette consumption, age of initiation and smoking duration. The Family
Based Association Test, an extension of the Transmission Disequilibrium Test, was
used to perform family-based association analysis. RESULTS: The Family Based
Association Test showed statistically significant association between the
rs2072658 polymorphism of the CHRNB2 gene and smoking-related phenotypes such as:
smoking status (SS), age of onset (AO), years of smoking, and psychological
dependence (PD) evaluated by the Glover-Nilsson Smoking Behavior Questionnaire.
After Bonferroni correction, only the association with AO remained significant (P
= .003). Statistically significant association was also observed for the CYP2A6
rs28399433 T allele with SS (P = .003) and PD (P = .003). CONCLUSIONS: Our
results indicate effects of the rs2072658 CHRNB2 and rs28399433 CYP2A6 gene
variants on AO, SS and PD in Mexican Mestizo smokers. A mild effect of other
analyzed gene variants, which may contribute to a putative polygenic
predisposition for smoking, is suggested. IMPLICATIONS: The understanding of
genetic and environmental determinants in the Mexican population is important for
other Latin American populations as well, living in their own countries or moving
to other ones, particular due to the current migration characteristics and
particular genetic background like the Mexican Mestizo and other Central American
populations with similar characteristics and migrating to neighbor developed
countries, introducing their own smoking behavior and contributing importantly to
the genetic pool of the receptor country.
PMID- 26416827
TI - Lumacaftor and ivacaftor in the management of patients with cystic fibrosis:
current evidence and future prospects.
AB - Cystic fibrosis (CF) is a genetic disorder that causes multiorgan morbidity and
premature death, most commonly from pulmonary dysfunction. Mutations in the CF
transmembrane conductance regulator (CFTR) gene, of which almost 2000 have been
described, result in a dysfunctional CFTR protein. This protein is an adenosine
triphosphate binding anion channel, present primarily at the surface of
epithelial cells. Loss of function mutations in this anion channel result in
decreased or absent chloride/bicarbonate transport. The subsequent abnormal salt
and water transport at epithelial cell surfaces leads to thickened secretions,
and infection or inflammation in affected organs. In the last 20 years,
therapeutics have been developed to treat the signs and symptoms of CF. However,
in 2012, the small molecule drug, ivacaftor, became the first approved therapy
that addresses the basic defect in CF. Ivacaftor is a potentiator of CFTR
channels defective in their chloride/bicarbonate gating/conductance, but present
at the epithelial cell surface. It is only approved for 10 mutations carried by
approximately 7% of the population of patients with CF. F508del is the most
common CFTR mutation, present in homozygosity in approximately 50% of patients
with CF. The F508del mutation results in multiple CFTR channel defects that
require both correction (stabilization of misfolded CFTR and trafficking to the
epithelial cell membrane) and potentiation. This article reviews the in vitro and
clinical trial data for the potential use of the potentiator, ivacaftor, and the
corrector, lumacaftor, in patients with CF.
PMID- 26416828
TI - Commentary: Key Issues, Concluding Thoughts, and Future Directions for the Study
of Trauma and Child Health.
PMID- 26416826
TI - Recent advances in central congenital hypothyroidism.
AB - Central congenital hypothyroidism (CCH) may occur in isolation, or more
frequently in combination with additional pituitary hormone deficits with or
without associated extrapituitary abnormalities. Although uncommon, it may be
more prevalent than previously thought, affecting up to 1:16 000 neonates in the
Netherlands. Since TSH is not elevated, CCH will evade diagnosis in primary, TSH
based, CH screening programs and delayed detection may result in
neurodevelopmental delay due to untreated neonatal hypothyroidism. Alternatively,
coexisting growth hormones or ACTH deficiency may pose additional risks, such as
life threatening hypoglycaemia. Genetic ascertainment is possible in a minority
of cases and reveals mutations in genes controlling the TSH biosynthetic pathway
(TSHB, TRHR, IGSF1) in isolated TSH deficiency, or early (HESX1, LHX3, LHX4,
SOX3, OTX2) or late (PROP1, POU1F1) pituitary transcription factors in combined
hormone deficits. Since TSH cannot be used as an indicator of euthyroidism,
adequacy of treatment can be difficult to monitor due to a paucity of alternative
biomarkers. This review will summarize the normal physiology of pituitary
development and the hypothalamic-pituitary-thyroid axis, then describe known
genetic causes of isolated central hypothyroidism and combined pituitary hormone
deficits associated with TSH deficiency. Difficulties in diagnosis and management
of these conditions will then be discussed.
PMID- 26416829
TI - Response of Vibrio cholerae to the Catecholamine Hormones Epinephrine and
Norepinephrine.
AB - In Escherichia coli or Salmonella enterica, the stress-associated mammalian
hormones epinephrine (E) and norepinephrine (NE) trigger a signaling cascade by
interacting with the QseC sensor protein. Here we show that Vibrio cholerae, the
causative agent of cholera, exhibits a specific response to E and NE. These
catecholates (0.1 mM) enhanced the growth and swimming motility of V. cholerae
strain O395 on soft agar in a medium containing calf serum, which simulated the
environment within the host. During growth, the hormones were converted to
degradation products, including adrenochrome formed by autooxidation with O2 or
superoxide. In E. coli, the QseC sensor kinase, which detects the autoinducer AI
3, also senses E or NE. The genome of V. cholerae O395 comprises an open reading
frame coding for a putative protein with 29% identity to E. coli QseC.
Quantitative reverse transcriptase PCR (qRT-PCR) experiments revealed increased
transcript levels of the qseC-like gene and of pomB, a gene encoding a structural
component of the flagellar motor complex, under the influence of E or NE.
Phentolamine blocks the response of E. coli QseC to E or NE. A V. cholerae mutant
devoid of the qseC-like gene retained the phentolamine-sensitive motility in the
presence of E, whereas NE-stimulated motility was no longer inhibited by
phentolamine. Our study demonstrates that V. cholerae senses the stress hormones
E and NE. A sensor related to the histidine kinase QseC from E. coli is
identified and is proposed to participate in the sensing of NE. IMPORTANCE:
Vibrio cholerae is a Gram-negative bacterium that may cause cholera, a severe
illness with high mortality due to acute dehydration caused by diarrhea and
vomiting. Pathogenic V. cholerae strains possess virulence factors like the
cholera toxin (CTX) and the toxin-coregulated pilus (TCP) produced in response to
signals provided by the host. In pathogenic enterobacteria, the stress-associated
hormones epinephrine (E) and norepinephrine (NE) of the human host act as signal
molecules for the production of virulence factors and promote bacterial growth by
the sequestration of iron from the host. Here we show that V. cholerae, like some
enterobacteria, benefits from these stress hormones and possesses a sensor to
recognize them.
PMID- 26416830
TI - In Silico Discovery and In Vitro Validation of Catechol-Containing
Sulfonohydrazide Compounds as Potent Inhibitors of the Diguanylate Cyclase PleD.
AB - Biofilm formation is responsible for increased antibiotic tolerance in pathogenic
bacteria. Cyclic di-GMP (c-di-GMP) is a widely used second-messenger signal that
plays a key role in bacterial biofilm formation. c-di-GMP is synthesized by
diguanylate cyclases (DGCs), a conserved class of enzymes absent in mammals and
hence considered attractive molecular targets for the development of antibiofilm
agents. Here, the results of a virtual screening approach aimed at identifying
small-molecule inhibitors of the DGC PleD from Caulobacter crescentus are
described. A three-dimensional (3D) pharmacophore model, derived from the mode of
binding of GTP to the active site of PleD, was exploited to screen the ZINC
database of compounds. Seven virtual hits were tested in vitro for their ability
to inhibit the activity of purified PleD by using circular dichroism
spectroscopy. Two drug-like molecules with a catechol moiety and a
sulfonohydrazide scaffold were shown to competitively inhibit PleD at the low
micromolar range (50% inhibitory concentration [IC50] of ~11 MUM). Their
predicted binding mode highlighted key structural features presumably responsible
for the efficient inhibition of PleD by both hits. These molecules represent the
most potent in vitro inhibitors of PleD identified so far and could therefore
result in useful leads for the development of novel classes of antimicrobials
able to hamper biofilm formation. IMPORTANCE: Biofilm-mediated infections are
difficult to eradicate, posing a threatening health issue worldwide. The
capability of bacteria to form biofilms is almost universally stimulated by the
second messenger c-di-GMP. This evidence has boosted research in the last decade
for the development of new antibiofilm strategies interfering with c-di-GMP
metabolism. Here, two potent inhibitors of c-di-GMP synthesis have been
identified in silico and characterized in vitro by using the well-characterized
DGC enzyme PleD from C. crescentus as a structural template and molecular target.
Given that the protein residues implied as crucial for enzyme inhibition are
found to be highly conserved among DGCs, the outcome of this study could pave the
way for the future development of broad-spectrum antibiofilm compounds.
PMID- 26416831
TI - An Electrostatic Net Model for the Role of Extracellular DNA in Biofilm Formation
by Staphylococcus aureus.
AB - Staphylococcus aureus is an important human pathogen that can form biofilms on
various surfaces. These cell communities are protected from the environment by a
self-produced extracellular matrix composed of proteins, DNA, and polysaccharide.
The exact compositions and roles of the different components are not fully
understood. In this study, we investigated the role of extracellular DNA (eDNA)
and its interaction with the recently identified cytoplasmic proteins that have a
moonlighting role in the biofilm matrix. These matrix proteins associate with the
cell surface upon the drop in pH that naturally occurs during biofilm formation,
and we found here that this association is independent of eDNA. Conversely, the
association of eDNA with the matrix was dependent on matrix proteins. Both
proteinase and DNase treatments severely reduced clumping of resuspended
biofilms; highlighting the importance of both proteins and eDNA in connecting
cells together. By adding an excess of exogenous DNA to DNase-treated biofilm,
clumping was partially restored, confirming the crucial role of eDNA in the
interconnection of cells. On the basis of our results, we propose that eDNA acts
as an electrostatic net, interconnecting cells surrounded by positively charged
matrix proteins at a low pH. IMPORTANCE: Extracellular DNA (eDNA) is an important
component of the biofilm matrix of diverse bacteria, but its role in biofilm
formation is not well understood. Here we report that in Staphylococcus aureus,
eDNA associates with cells in a manner that depends on matrix proteins and that
eDNA is required to link cells together in the biofilm. These results confirm
previous studies that showed that eDNA is an important component of the S. aureus
biofilm matrix and also suggest that eDNA acts as an electrostatic net that
tethers cells together via the proteinaceous layer of the biofilm matrix.
PMID- 26416832
TI - AraR, an l-Arabinose-Responsive Transcriptional Regulator in Corynebacterium
glutamicum ATCC 31831, Exerts Different Degrees of Repression Depending on the
Location of Its Binding Sites within the Three Target Promoter Regions.
AB - In Corynebacterium glutamicum ATCC 31831, a LacI-type transcriptional regulator
AraR, represses the expression of l-arabinose catabolism (araBDA), uptake (araE),
and the regulator (araR) genes clustered on the chromosome. AraR binds to three
sites: one (BSB) between the divergent operons (araBDA and galM-araR) and two
(BSE1 and BSE2) upstream of araE. L-Arabinose acts as an inducer of the AraR
mediated regulation. Here, we examined the roles of these AraR-binding sites in
the expression of the AraR regulon. BSB mutation resulted in derepression of both
araBDA and galM-araR operons. The effects of BSE1 and/or BSE2 mutation on araE
expression revealed that the two sites independently function as the cis
elements, but BSE1 plays the primary role. However, AraR was shown to bind to
these sites with almost the same affinity in vitro. Taken together, the
expression of araBDA and araE is strongly repressed by binding of AraR to a
single site immediately downstream of the respective transcriptional start sites,
whereas the binding site overlapping the -10 or -35 region of the galM-araR and
araE promoters is less effective in repression. Furthermore, downregulation of
araBDA and araE dependent on l-arabinose catabolism observed in the BSB mutant
and the AraR-independent araR promoter identified within galM-araR add complexity
to regulation of the AraR regulon derepressed by L-arabinose. IMPORTANCE:
Corynebacterium glutamicum has a long history as an industrial workhorse for
large-scale production of amino acids. An important aspect of industrial
microorganisms is the utilization of the broad range of sugars for cell growth
and production process. Most C. glutamicum strains are unable to use a pentose
sugar L-arabinose as a carbon source. However, genes for L-arabinose utilization
and its regulation have been recently identified in C. glutamicum ATCC 31831.
This study elucidates the roles of the multiple binding sites of the
transcriptional repressor AraR in the derepression by L-arabinose and thereby
highlights the complex regulatory feedback loops in combination with l-arabinose
catabolism-dependent repression of the AraR regulon in an AraR-independent
manner.
PMID- 26416833
TI - Evolution of Mycolic Acid Biosynthesis Genes and Their Regulation during
Starvation in Mycobacterium tuberculosis.
AB - Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a Gram
positive bacterium with a unique cell envelope composed of an essential outer
membrane. Mycolic acids, which are very-long-chain (up to C100) fatty acids, are
the major components of this mycomembrane. The enzymatic pathways involved in the
biosynthesis and transport of mycolates are fairly well documented and are the
targets of the major antituberculous drugs. In contrast, only fragmented
information is available on the expression and regulation of the biosynthesis
genes. In this study, we report that the hadA, hadB, and hadC genes, which code
for the mycolate biosynthesis dehydratase enzymes, are coexpressed with three
genes that encode proteins of the translational apparatus. Consistent with the
well-established control of the translation potential by nutrient availability,
starvation leads to downregulation of the hadABC genes along with most of the
genes required for the synthesis, modification, and transport of mycolates. The
downregulation of a subset of the biosynthesis genes is partially dependent on
RelMtb, the key enzyme of the stringent response. We also report the phylogenetic
evolution scenario that has shaped the current genetic organization,
characterized by the coregulation of the hadABC operon with genes of the
translational apparatus and with genes required for the modification of the
mycolates. IMPORTANCE: Mycobacterium tuberculosis infects one-third of the human
population worldwide, and despite the available therapeutic arsenal, it continues
to kill millions of people each year. There is therefore an urgent need to
identify new targets and develop a better understanding of how the bacterium is
adapting itself to host defenses during infection. A prerequisite of this
understanding is knowledge of how this adaptive skill has been implanted by
evolution. Nutrient scarcity is an environmental condition the bacterium has to
cope with during infection. In many bacteria, adaptation to starvation relies
partly on the stringent response. M. tuberculosis's unique outer membrane layer,
the mycomembrane, is crucial for its viability and virulence. Despite its being
the target of the major antituberculosis drugs, only scattered information exists
on how the genes required for biosynthesis of the mycomembrane are expressed and
regulated during starvation. This work has addressed this issue as a step toward
the identification of new targets in the fight against M. tuberculosis.
PMID- 26416835
TI - Disparate worlds drawing closer together: cardiovascular biomarkers predict
cancer outcomes in treatment-naive patients.
PMID- 26416834
TI - The Sugar Kinase That Is Necessary for the Catabolism of Rhamnose in Rhizobium
leguminosarum Directly Interacts with the ABC Transporter Necessary for Rhamnose
Transport.
AB - Rhamnose catabolism in Rhizobium leguminosarum was found to be necessary for the
ability of the organism to compete for nodule occupancy. Characterization of the
locus necessary for the catabolism of rhamnose showed that the transport of
rhamnose was dependent upon a carbohydrate uptake transporter 2 (CUT2) ABC
transporter encoded by rhaSTPQ and on the presence of RhaK, a protein known to
have sugar kinase activity. A linker-scanning mutagenesis analysis of rhaK showed
that the kinase and transport activities of RhaK could be separated genetically.
More specifically, two pentapeptide insertions defined by the alleles rhaK72 and
rhaK73 were able to uncouple the transport and kinase activities of RhaK, such
that the kinase activity was retained, but cells carrying these alleles did not
have measurable rhamnose transport rates. These linker-scanning alleles were
localized to the C terminus and N terminus of RhaK, respectively. Taken together,
the data led to the hypothesis that RhaK might interact either directly or
indirectly with the ABC transporter defined by rhaSTPQ. In this work, we show
that both N- and C-terminal fragments of RhaK are capable of interacting with the
N-terminal fragment of the ABC protein RhaT using a 2-hybrid system. Moreover, if
RhaK fragments carrying either the rhaK72 or rhaK73 allele were used, this
interaction was abolished. Phylogenetic and bioinformatic analysis of the RhaK
fragments suggested that a conserved region in the N terminus of RhaK may
represent a putative binding domain. Alanine-scanning mutagenesis of this region
followed by 2-hybrid analysis revealed that a substitution of any of the
conserved residues greatly affected the interaction between RhaT and RhaK
fragments, suggesting that the sugar kinase RhaK and the ABC protein RhaT
interact directly. IMPORTANCE: ABC transporters involved in the transport of
carbohydrates help define the overall physiological fitness of bacteria. The two
largest groups of transporters are the carbohydrate uptake transporter classes 1
and 2 (CUT1 and CUT2, respectively). This work provides the first evidence that a
kinase that is necessary for the catabolism of a sugar can directly interact with
a domain from the ABC protein that is necessary for its transport.
PMID- 26416836
TI - Cardiovascular biomarkers in patients with cancer and their association with all
cause mortality.
AB - OBJECTIVE: Patients with cancer may display elevated levels of B-type natriuretic
peptide (BNP) and high-sensitive troponin T (hsTnT) without clinical
manifestation of cardiac disease. This study aimed to evaluate circulating
cardiovascular hormones and hsTnT and their association with mortality in cancer.
METHODS: We prospectively enrolled 555 consecutive patients with a primary
diagnosis of cancer and without prior cardiotoxic anticancer therapy. N-terminal
pro BNP (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid
regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET
1), copeptin, hsTnT, proinflammatory markers interleukin 6 (IL-6) and C reactive
protein (CRP), and cytokines serum amyloid A (SAA), haptoglobin and fibronectin
were measured. All-cause mortality was defined as primary endpoint. RESULTS:
During a median follow-up of 25 (IQR 16-31) months, 186 (34%) patients died. All
cardiovascular hormones and hsTnT levels rose with tumour stage progression. All
markers were significant predictors of mortality with HRs per IQR of 1.54 (95% CI
1.24 to 1.90, p<0.001) for NT-proBNP, 1.40 (95% CI 1.10 to 1.79, p<0.01) for MR
proANP, 1.31 (95% CI 1.19 to 1.44, p<0.001) for MR-proADM, 1.21 (95% CI 1.14 to
1.30, p<0.001) for CT-proET-1, 1.22 (95% CI 1.04 to 1.42, p=0.014) for copeptin
and 1.21 (95% CI 1.13 to 1.32, p<0.001) for hsTnT, independent of age, gender,
tumour entity and stage, and presence of cardiac comorbidities. NT-proBNP, MR
proANP, MR-proADM and hsTnT displayed a significant correlation with IL-6 and
CRP. CONCLUSIONS: Circulating levels of cardiovascular peptides like NT-proBNP,
MR-proANP, MR-proADM, CT-pro-ET-1 and hsTnT were elevated in an unselected
population of patients with cancer prior to induction of any cardiotoxic
anticancer therapy. The aforementioned markers and copeptin were strongly related
to all-cause mortality, suggesting the presence of subclinical functional and
morphological myocardial damage directly linked to disease progression.
PMID- 26416837
TI - Very abnormal T waves in a 37-year-old man.
PMID- 26416838
TI - The reciprocal interaction between LV remodelling and allograft outcomes in
kidney transplant recipients.
AB - OBJECTIVE: This study aimed to investigate the incidence and related clinical
factors of LV hypertrophy (LVH) regression after kidney transplantation and its
effect on graft outcome. METHODS: Among the 3373 kidney transplant recipients who
were enrolled in a multicentre cohort from 1997 to 2012, a total of 767 patients
who underwent echocardiography before and after transplantation were included in
this study followed for a median of 7.5 years. RESULTS: LVH regression steadily
increased from 7.4% at 1 year to 35.4% at 5 year over the 5-year post
transplantation period. The probability of LVH regression decreased in the
patients who received a kidney transplant due to end-stage renal disease of
unknown aetiology (p=0.041) or who underwent pretransplant haemodialysis
(p=0.020). The probability of LVH regression also decreased as the pretransplant
LV mass index (p<0.001) and post-transplant systolic blood pressure increased
(p=0.005). Conversely, LVH regression was significantly associated with the
highest tertile of the pretransplant haemoglobin level (p=0.029). Furthermore, in
the 5th year after transplantation, persistent LVH was independently associated
with allograft failure (HR 1.95; 95% CI 1.14 to 3.33; p=0.015) and the LV mass
index reliably predicted graft outcome. CONCLUSIONS: LVH consistently regressed
after kidney transplantation in most patients. Persistent LVH, low haemoglobin
levels and elevated blood pressure were associated with an increased risk of
allograft failure in kidney transplant recipients.
PMID- 26416840
TI - Two different nucleotide substitutions of APC gene in a family with familial
adenomatous polyposis.
AB - Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome leading to
colorectal cancer. This disease appears as a result of germline mutation in
adenomatous polyposis coli (APC) gene. The aim of the present study is to report
the association between two different nucleotide substitutions detected in a
family with FAP. In the proband, p.His1172Gln (c.3516delT) was detected in exon
15 of the APC gene. Furthermore, p.His1172Gln (c.3516delT) and, in addition to
this mutation, p.Met1413Val (c.4237 A > G) were detected in exon 15 in both
daughters of the proband. However, we believe that single nucleotide change in
codon 1413 may be a polymorphic variant and deletion T in codon 1172 of APC gene
is associated with FAP, attenuated FAP and extracolonic FAP involvement. Along
with common use of genetic tests in the clinical practice, genotype-phenotype
correlation may be recognized better and useful for early diagnosis and
prevention of familial cancer syndromes.
PMID- 26416839
TI - Backscatter-difference Measurements of Cancellous Bone Using an Ultrasonic
Imaging System.
AB - Backscatter-difference measurements may be used to detect changes in bone caused
by osteoporosis. The backscatter-difference technique measures the power
difference between two portions of an ultrasonic backscatter signal. The goal of
this study is to evaluate the feasibility of using an ultrasonic imaging system
to perform backscatter-difference measurements of bone. Ultrasonic images and
backscatter signals were acquired from 24 specimens of human cancellous bone. The
signals were analyzed in the frequency domain to determine the normalized mean
backscatter-difference (nMBD) and in the time domain to determine the normalized
backscatter amplitude ratio (nBAR). The images were analyzed to determine the
normalized pixel value difference (nPVD), which measures the difference in
average pixel brightness between regions of interest placed at two different
depths in the image. All three parameters were found to increase with bone
mineral density. The signal-based parameters, nMBD and nBAR, correlated well with
bone mineral density, yielding linear correlation coefficients that ranged from
0.74 to 0.87. The image based parameter, nPVD, performed somewhat less well,
yielding correlation coefficients that ranged from 0.42 to 0.81. These results
suggest that ultrasonic imaging systems may be used to perform backscatter
difference measurements for the purpose of ultrasonic bone assessment.
PMID- 26416841
TI - "I Didn't Know Whether I Was Right or Wrong or Just Bewildered": Ambiguity,
Responsibility, and Silencing Women's Talk of Men's Domestic Violence.
AB - Little has been written about the impact on women of the man's obscuring and
deflecting of responsibility when domestic violence is used by him against her.
Women's advocates report that women who seek shelter from domestic violence
assume blame for the violence and struggle to shift from this position of
responsibility. Women are likely to be silenced if they assume responsibility and
are less likely to come forward. In this study, we use discourse analysis to
describe the ambiguities around responsibility that worked to silence 20 women
and the sociocultural influences that supported this ambiguity. We discuss the
implications for prevention.
PMID- 26416842
TI - Clergy Perceptions of Sexual Assault Victimization.
AB - Although congregants often turn to clergy for help in dealing with personal
difficulties, including marital problems, substance abuse issues, and mental
illness, survivors of sexual assault do not commonly turn to clergy for support
or guidance. This study utilized a mixed-methods approach, online survey, and
semi-structured interviews to determine how clergy perceive sexual assault
victimization. The results of this study showed that more blame was assigned to
the victim as the relationship with the perpetrator became closer, with the
exception of marital rape. This study also found that hostile sexism was a
predictor of negative attitudes toward rape victims.
PMID- 26416843
TI - Depressive symptoms and psychosocial aspects of work in bank employees.
AB - BACKGROUND: The financial sector has seen an increase in the number of cases of
violence and stress, which can result in adverse health outcomes, including
depressive symptoms, but studies related to stress at work and depression for
these workers are scarce. AIMS: To investigate the association between exposure
to psychosocial work stressors and depressive symptoms in bank employees.
METHODS: A self-administered questionnaire was completed by a sample of bank
employees in Para and Amapa, Brazil. The survey assessed sociodemographic
characteristics, mental health (Patient Health Questionnaire-9), Demand-Control
Support and Effort-Reward Imbalance (ERI). Outcomes included two levels of
depressive symptoms: major depressive symptoms (MDS) and other forms of
depressive symptoms (ODS). Logistic regression models were used to estimate
associations between depressive symptoms, the two job stress models and relevant
covariates. RESULTS: Of 2806 eligible subjects, there were 1445 respondents (52%
response rate) and the final analyses included 1046 participants. The overall
prevalence of depressive symptoms was 32% (MDS = 18%; ODS = 14%), with no
statistically significant difference between men and women. High demands, low
levels of control and low social support were associated with MDS and/or ODS,
adjusted for gender, age and other work-related conditions. High effort/low
reward, over-commitment and ERI were also associated with MDS and ODS.
CONCLUSIONS: Psychosocial conditions in banking activity involving high strain,
low social support at work, high effort with low reward and over-commitment may
represent possible risk factors for depressive symptoms in bank employees.
PMID- 26416844
TI - Neck and upper back pain among eye care professionals.
AB - BACKGROUND: Ophthalmologists and optometrists have reported a higher prevalence
of neck, hand/wrist and lower back pain than family medicine physicians. Work
related musculoskeletal disorders have not previously been studied in Saudi eye
care professionals. AIMS: To determine the magnitude and determinants of neck and
upper back pain among eye care professionals at a tertiary hospital in Saudi
Arabia in 2013. METHODS: A cross-sectional study using a close-ended
questionnaire to determine the frequency of neck and back pain and its
association with age, sex, weight, comorbidities, duration of professional work,
history of injury and physician sub-speciality. RESULTS: The response rate was
82% and 165 eye care professionals participated, 70% (113) of whom reported neck
and back pain. The rate was similar in ophthalmologists and allied eye care
professionals and among surgical and medical ophthalmologists. The prevalence
rate of neck and upper back pain was not associated with number of years in the
profession, comorbidities, self-reported weight or injury. Pain appeared to be
associated with reported physical discomfort during professional activities (P <
0.01) but not with mental stress. Pain was thought to be work related by 50% of
participants. A lower rate of neck and upper back pain was associated with
regular exercise [odds ratio = 0.5 (95% confidence interval 0.2-0.9)].
CONCLUSIONS: Neck and back pain was reported by 70% of eye care professionals.
The pain was graded as mild to moderate and improved when on holidays. Regular
physical exercise appeared to prevent or reduce neck and upper back pain.
PMID- 26416845
TI - Lymphocytic choriomeningitis virus infection induced by percutaneous exposure.
AB - We report a case of acquired lymphocytic choriomeningitis virus (LCMV) infection
due to an accidental percutaneous inoculation of LCMV at work. The injured worker
developed a flu-like syndrome, followed by pericarditis and meningoencephalitis.
Seroconversion was confirmed by ELISA. The patient made a complete recovery. We
review measures undertaken to prevent a similar event and propose a follow-up
protocol in the event of accidental LCMV exposure.
PMID- 26416846
TI - Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood
Pressure via the Rostral Ventrolateral Medulla.
AB - Elevated NaCl concentrations of the cerebrospinal fluid increase sympathetic
nerve activity (SNA) in salt-sensitive hypertension. Neurons of the rostral
ventrolateral medulla (RVLM) play a pivotal role in the regulation of SNA and
receive mono- or polysynaptic inputs from several hypothalamic structures
responsive to hypernatremia. Therefore, the present study investigated the
contribution of RVLM neurons to the SNA and pressor response to cerebrospinal
fluid hypernatremia. Lateral ventricle infusion of 0.15 mol/L, 0.6 mol/L, and 1.0
mol/L NaCl (5 uL/10 minutes) produced concentration-dependent increases in lumbar
SNA, adrenal SNA, and arterial blood pressure, despite no change in splanchnic
SNA and a decrease in renal SNA. Ganglionic blockade with chlorisondamine or
acute lesion of the lamina terminalis blocked or significantly attenuated these
responses, respectively. RVLM microinjection of the gamma-aminobutyric acid
(GABAA) agonist muscimol abolished the sympathoexcitatory response to
intracerebroventricular infusion of 1 mol/L NaCl. Furthermore, blockade of
ionotropic glutamate, but not angiotensin II type 1, receptors significantly
attenuated the increase in lumbar SNA, adrenal SNA, and arterial blood pressure.
Finally, single-unit recordings of spinally projecting RVLM neurons revealed 3
distinct populations based on discharge responses to intracerebroventricular
infusion of 1 mol/L NaCl: type I excited (46%; 11/24), type II inhibited (37%;
9/24), and type III no change (17%; 4/24). All neurons with slow conduction
velocities were type I cells. Collectively, these findings suggest that acute
increases in cerebrospinal fluid NaCl concentrations selectively activate a
discrete population of RVLM neurons through glutamate receptor activation to
increase SNA and arterial blood pressure.
PMID- 26416847
TI - Generation of Hypertension-Associated STK39 Polymorphism Knockin Cell Lines With
the Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 System.
AB - Previous genome-wide association studies identified serine threonine kinase 39
(STK39), encoding STE20/SPS1-related proline/alanine-rich kinase, as one of a
limited number of hypertension susceptibility genes. A recent meta-analysis
confirmed the association of STK39 intronic polymorphism rs3754777 with essential
hypertension, among previously reported hypertension-associated STK39
polymorphisms. However, the biochemical function of this polymorphism in the
mechanism responsible for hypertension is yet to be clarified. We generated
rs3754777G>A knockin human cell lines with clustered regularly interspaced short
palindromic repeats-mediated genome engineering. Homozygous (A/A) and
heterozygous (G/A) knockin human embryonic kidney cell lines were generated using
a double nickase, single-guide RNAs targeting STK39 intron 5 around single
nucleotide polymorphism, and a 100-bp donor single-stranded DNA oligonucleotide.
Reverse transcription polymerase chain reaction with sequencing analyses revealed
the identical STK39 transcripts among the wild-type and both knockin cell lines.
Quantitative reverse transcription polymerase chain reaction showed increased
STK39 mRNA expression, and immunoblot analysis revealed increases in total and
phosphorylated STE20/SPS1-related proline/alanine-rich kinase with increased
phosphorylated Na-K-Cl cotransporter isoform 1 in both knockin cell lines. The
largest increases in these molecules were observed in the homozygous cell line.
These findings indicated that this intronic polymorphism increases STK39
transcription, leading to activation of the STE20/SPS1-related proline/alanine
rich kinase-solute carrier family 12A signaling cascade. Increased interactions
between STE20/SPS1-related proline/alanine-rich kinase and the target cation
chloride cotransporters may be responsible for hypertension susceptibility in
individuals with this polymorphism.
PMID- 26416850
TI - A tale of five cities: Using recycling frameworks to analyse inclusive recycling
performance.
AB - 'Recycling' is a source of much confusion, particularly when comparing solid
waste systems in high-income countries with those in low- and middle-income
countries. Few analysts can explain why the performance and structure of
recycling appears to be so different in rich countries from poor ones, nor why
well-meaning efforts to implement recycling so often fail. The analysis of policy
drivers, and the Integrated Sustainable Waste Management (ISWM) framework, come
close to an explanation.This article builds on these earlier works, focusing in
on five cities profiled in the 2010 UN-Habitat publication (Scheinberg A, Wilson
DC and Rodic L (2010) Solid Waste Management in the World's Cities. UN-Habitat's
Third Global Report on the State of Water and Sanitation in the World's Cities.
Newcastle-on-Tyne, UK: Earthscan Publications). Data from these cities and others
provides the basis for developing a new tool to analyse inclusive recycling
performance. The points of departure are the institutional and economic
relationships between the service chain, the public obligation to remove waste,
pollution, and other forms of disvalue, and the value chain, a system of private
enterprises trading valuable materials and providing markets for recyclables. The
methodological innovation is to use flows of materials and money as indicators of
institutional relationships, and is an extension of process flow diagramming.The
authors are using the term 'recycling framework analysis' to describe this new
form of institutional analysis. The diagrams increase our understanding of the
factors that contribute to high-performance inclusive recycling. By focusing on
institutional relationships, the article seeks to improve analysis, planning, and
ultimately, outcomes, of recycling interventions.
PMID- 26416848
TI - Adenosine Attenuates Human Coronary Artery Smooth Muscle Cell Proliferation by
Inhibiting Multiple Signaling Pathways That Converge on Cyclin D.
AB - The goal of this study was to determine whether and how adenosine affects the
proliferation of human coronary artery smooth muscle cells (HCASMCs). In HCASMCs,
2-chloroadenosine (stable adenosine analogue), but not N(6)-cyclopentyladenosine,
CGS21680, or N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide, inhibited HCASMC
proliferation (A2B receptor profile). 2-Chloroadenosine increased cAMP, reduced
phosphorylation (activation) of ERK and Akt (protein kinases known to increase
cyclin D expression and activity, respectively), and reduced levels of cyclin D1
(cyclin that promotes cell-cycle progression in G1). Moreover, 2-chloroadenosine
inhibited expression of S-phase kinase-associated protein-2 (Skp2; promotes
proteolysis of p27(Kip1)) and upregulated levels of p27(Kip1) (cell-cycle
regulator that impairs cyclin D function). 2-Chloroadenosine also inhibited
signaling downstream of cyclin D, including hyperphosphorylation of
retinoblastoma protein and expression of cyclin A (S phase cyclin). Knockdown of
A2B receptors prevented the effects of 2-chloroadenosine on ERK1/2, Akt, Skp2,
p27(Kip1), cyclin D1, cyclin A, and proliferation. Likewise, inhibition of
adenylyl cyclase and protein kinase A abrogated 2-chloroadenosine's inhibitory
effects on Skp2 and stimulatory effects on p27(Kip1) and rescued HCASMCs from 2
chloroadenosine-mediated inhibition. Knockdown of p27(Kip1) also reversed the
inhibitory effects of 2-chloroadenosine on HCASMC proliferation. In vivo, peri
arterial (rat carotid artery) 2-chloroadenosine (20 MUmol/L for 7 days)
downregulated vascular expression of Skp2, upregulated vascular expression of
p27(Kip1), and reduced neointima hyperplasia by 71% (P<0.05; neointimal
thickness: control, 37 424+/-18 371 pixels; treated, 10 352+/-2824 pixels). In
conclusion, the adenosine/A2B receptor/cAMP/protein kinase A axis inhibits HCASMC
proliferation by blocking multiple signaling pathways (ERK1/2, Akt, and Skp2)
that converge at cyclin D, a key G1 cyclin that controls cell-cycle progression.
PMID- 26416849
TI - Placental-Specific sFLT-1 e15a Protein Is Increased in Preeclampsia, Antagonizes
Vascular Endothelial Growth Factor Signaling, and Has Antiangiogenic Activity.
AB - In preeclampsia, the antiangiogenic factor soluble fms-like tyrosine kinase-1
(sFLT-1) is released from placenta into the maternal circulation, causing
endothelial dysfunction and organ injury. A recently described splice variant,
sFLT-1 e15a, is primate specific and the most abundant placentally derived sFLT
1. Therefore, it may be the major sFLT-1 isoform contributing to the
pathophysiology of preeclampsia. sFLT-1 e15a protein remains poorly
characterized: its bioactivity has not been comprehensively examined, and serum
levels in normal and preeclamptic pregnancy have not been reported. We generated
and validated an sFLT-1 e15a-specific ELISA to further characterize serum levels
during pregnancy, and in the presence of preeclampsia. Furthermore, we performed
assays to examine the bioactivity and antiangiogenic properties of sFLT-1 e15a
protein. sFLT-1 e15a was expressed in the syncytiotrophoblast, and serum levels
rose across pregnancy. Strikingly, serum levels were increased 10-fold in preterm
preeclampsia compared with normotensive controls. We confirmed sFLT-1 e15a is
bioactive and is able to inhibit vascular endothelial growth factor signaling of
vascular endothelial growth factor receptor 2 and block downstream Akt
phosphorylation. Furthermore, sFLT-1 e15a has antiangiogenic properties. sFLT-1
e15a decreased endothelial cell migration, invasion, and inhibited endothelial
cell tube formation. Administering sFLT-1 e15a blocked vascular endothelial
growth factor induced sprouts from mouse aortic rings ex vivo. We have
demonstrated that sFLT-1 e15a is increased in preeclampsia, antagonizes vascular
endothelial growth factor signaling, and has antiangiogenic activity. Future
development of diagnostics and therapeutics for preeclampsia should consider
targeting placentally derived sFLT-1 e15a.
PMID- 26416851
TI - Comparison of alternative remediation technologies for recycled gravel
contaminated with heavy metals.
AB - To evaluate the effects of different remediation methods on heavy metals
contaminated recycled gravel, three immobilization agents (monopotassium
phosphate, lime, nano-iron) and two mobilization agents (glyphosate, humic acid
(HA)) were studied and compared. Results indicated that nano-iron powder was
found to be more effective to immobilize Zn, Cu, Pb and Cd. Meanwhile, glyphosate
presents a higher mobilization effect than HA with removal rates of about 66.7%
for Cd, more than 80% for Cr, Cu and Zn, and the highest removal percentage of
85.9% for Cr. After the mobilization by glyphosate, the leaching rates of Zn, Cu
and Cr were about 0.8%, and below 0.2% for Pb and Cd. The leaching rates after
nano-iron powder treatment were 1.18% for Zn, 0.96% for Cr, 0.61% for Cu, 0.45%
for Pb and Cd not detected. The formation and disappearance of metal
(Zn/Cu/Cr/Pb/Cd) compounds were firmly confirmed through X-ray diffraction and
scanning electron microscopy analyses on crystalline phases and morphological
surface structures.
PMID- 26416852
TI - Arabidopsis Intracellular NHX-Type Sodium-Proton Antiporters are Required for
Seed Storage Protein Processing.
AB - The Arabidopsis intracellular sodium-proton exchanger (NHX) proteins AtNHX5 and
AtNHX6 have a well-documented role in plant development, and have been used to
improve salt tolerance in a variety of species. Despite evidence that
intracellular NHX proteins are important in vacuolar trafficking, the mechanism
of this role is poorly understood. Here we show that NHX5 and NHX6 are necessary
for processing of the predominant seed storage proteins, and also influence the
processing and activity of a vacuolar processing enzyme. Furthermore, we show by
yeast two-hybrid and bimolecular fluorescence complementation (BiFC) technology
that the C-terminal tail of NHX6 interacts with a component of Retromer, another
component of the cell sorting machinery, and that this tail is critical for NHX6
activity. These findings demonstrate that NHX5 and NHX6 are important in
processing and activity of vacuolar cargo, and suggest a mechanism by which NHX
intracellular (IC)-II antiporters may be involved in subcellular trafficking.
PMID- 26416853
TI - Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable
Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates.
AB - A new category of cefepime susceptibility, susceptible dose dependent (SDD), for
Enterobacteriaceae, has been suggested to maximize its clinical use. However,
clinical evidence supporting such a therapeutic strategy is limited. A
retrospective study of 305 adults with monomicrobial Enterobacter cloacae
bacteremia at a medical center from 2008 to 2012 was conducted. The patients
definitively treated with in vitro active cefepime (cases) were compared with
those treated with a carbapenem (controls) to assess therapeutic effectiveness.
The 30-day crude mortality rate is the primary endpoint, and clinical prognostic
factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem
therapy, there were no significant differences in terms of age, sex, comorbidity,
source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%;
P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In
the multivariate analysis, the presence of critical illness, rapidly fatal
underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and
cefepime-SDD (cefepime MIC, 4 to 8 MUg/ml) isolates was independently associated
with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with
definitive cefepime therapy had a higher mortality rate than those treated with a
carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P = 0.045). Cefepime is one of the
therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is
inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with
carbapenem therapy.
PMID- 26416854
TI - Fitness Studies of Azole-Resistant Strains of Aspergillus fumigatus.
AB - Isogenic bar-coded strains of Aspergillus fumigatus carrying the G54W or M220K
mutation in Cyp51A were constructed. In vitro, the growth and conidiation
capacities of the mutants were similar to those of the parental strain.
Competition studies in the absence of azoles showed that there was no adverse
fitness cost for the azole-resistant A. fumigatus strains in vitro or in vivo
compared to the parental strain.
PMID- 26416855
TI - Efficacy of humanized high-dose meropenem, cefepime, and levofloxacin against
Enterobacteriaceae isolates producing Verona integron-encoded metallo-beta
lactamase (VIM) in a murine thigh infection model.
AB - We aimed to describe the in vivo activity of humanized pharmacokinetic exposures
of meropenem and comparators against Verona integron-encoded metallo-beta
lactamase (MBL) (VIM)-producing Enterobacteriaceae in a murine model.
Levofloxacin activity was predicted by its MIC, and cefepime activity displayed
variability, whereas meropenem produced a >1 log CFU reduction against all
isolates despite high MICs indicative of resistance. Our results suggest that
despite in vitro resistance, high-dose meropenem may be a possible option against
infections caused by Enterobacteriaceae producing MBL-type carbapenemases.
PMID- 26416857
TI - Different Therapeutic Outcomes of Benznidazole and VNI Treatments in Different
Genders in Mouse Experimental Models of Trypanosoma cruzi Infection.
AB - The lack of translation between preclinical assays and clinical trials for novel
therapies for Chagas disease (CD) indicates a need for more feasible and
standardized protocols and experimental models. Here, we investigated the effects
of treatment with benznidazole (Bz) and with the potent experimental T. cruzi
CYP51 inhibitor VNI in mouse models of Chagas disease by using different animal
genders and parasite strains and employing distinct types of therapeutic schemes.
Our findings confirm that female mice are less vulnerable to the infection than
males, show that male models are less susceptible to treatment with both Bz and
VNI, and thus suggest that male models are much more suitable for selection of
the most promising antichagasic agents. Additionally, we have found that
preventive protocols (compound given at 1 dpi) result in higher treatment success
rates, which also should be avoided during advanced steps of in vivo trials of
novel anti-T. cruzi drug candidates. Another consideration is the relevance of
immunosuppression methods in order to verify the therapeutic profile of novel
compounds, besides the usefulness of molecular diagnostic tools (quantitative
PCR) to ascertain compound efficacy in experimental animals. Our study aims to
contribute to the development of more reliable methods and decision gates for in
vivo assays of novel antiparasitic compounds in order to move them from
preclinical to clinical trials for CD.
PMID- 26416858
TI - Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the
Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant
Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model.
AB - There is growing interest in biomaterials that can cure bone infection and also
regenerate bone. In this study, two groups of implants composed of 10% (wt/wt)
teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium
sulfate (TCS) were created and evaluated for their ability to release TEC in
vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced
osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline
(PBS), both groups of implants provided a sustained release of TEC at a
therapeutic level for up to 3 to 4 weeks while they were gradually degraded and
converted to hydroxyapatite. The TBG implants showed a longer duration of TEC
release and better retention of strength as a function of immersion time in PBS.
Infected rabbit tibiae were treated by debridement, followed by implantation of
TBG or TCS pellets or intravenous injection with TEC, or were left untreated.
Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG
or TCS pellets had significantly lower radiological and histological scores,
lower rates of MRSA-positive cultures, and lower bacterial loads than those
preoperatively and those of animals treated intravenously. The level of bone
regeneration was also higher in the defects treated with the TBG pellets. The
results showed that local TEC delivery was more effective than intravenous
administration for the treatment of MRSA-induced osteomyelitis. Borate glass has
the advantages of better mechanical strength, more desirable kinetics of release
of TEC, and a higher osteogenic capacity and thus could be an effective
alternative to calcium sulfate for local delivery of TEC.
PMID- 26416856
TI - Genome Expression Profiling-Based Identification and Administration Efficacy of
Host-Directed Antimicrobial Drugs against Respiratory Infection by Nontypeable
Haemophilus influenzae.
AB - Therapies that are safe, effective, and not vulnerable to developing resistance
are highly desirable to counteract bacterial infections. Host-directed
therapeutics is an antimicrobial approach alternative to conventional antibiotics
based on perturbing host pathways subverted by pathogens during their life cycle
by using host-directed drugs. In this study, we identified and evaluated the
efficacy of a panel of host-directed drugs against respiratory infection by
nontypeable Haemophilus influenzae (NTHi). NTHi is an opportunistic pathogen that
is an important cause of exacerbation of chronic obstructive pulmonary disease
(COPD). We screened for host genes differentially expressed upon infection by the
clinical isolate NTHi375 by analyzing cell whole-genome expression profiling and
identified a repertoire of host target candidates that were pharmacologically
modulated. Based on the proposed relationship between NTHi intracellular location
and persistence, we hypothesized that drugs perturbing host pathways used by NTHi
to enter epithelial cells could have antimicrobial potential against NTHi
infection. Interfering drugs were tested for their effects on bacterial and
cellular viability, on NTHi-epithelial cell interplay, and on mouse pulmonary
infection. Glucocorticoids and statins lacked in vitro and/or in vivo efficacy.
Conversely, the sirtuin-1 activator resveratrol showed a bactericidal effect
against NTHi, and the PDE4 inhibitor rolipram showed therapeutic efficacy by
lowering NTHi375 counts intracellularly and in the lungs of infected mice. PDE4
inhibition is currently prescribed in COPD, and resveratrol is an attractive
geroprotector for COPD treatment. Together, these results expand our knowledge of
NTHi-triggered host subversion and frame the antimicrobial potential of rolipram
and resveratrol against NTHi respiratory infection.
PMID- 26416859
TI - Two Simple Rules for Improving the Accuracy of Empiric Treatment of Multidrug
Resistant Urinary Tract Infections.
AB - The emergence of multidrug-resistant (MDR) uropathogens is making the treatment
of urinary tract infections (UTIs) more challenging. We sought to evaluate the
accuracy of empiric therapy for MDR UTIs and the utility of prior culture data in
improving the accuracy of the therapy chosen. The electronic health records from
three U.S. Department of Veterans Affairs facilities were retrospectively
reviewed for the treatments used for MDR UTIs over 4 years. An MDR UTI was
defined as an infection caused by a uropathogen resistant to three or more
classes of drugs and identified by a clinician to require therapy. Previous data
on culture results, antimicrobial use, and outcomes were captured from records
from inpatient and outpatient settings. Among 126 patient episodes of MDR UTIs,
the choices of empiric therapy against the index pathogen were accurate in 66
(52%) episodes. For the 95 patient episodes for which prior microbiologic data
were available, when empiric therapy was concordant with the prior microbiologic
data, the rate of accuracy of the treatment against the uropathogen improved from
32% to 76% (odds ratio, 6.9; 95% confidence interval, 2.7 to 17.1; P < 0.001).
Genitourinary tract (GU)-directed agents (nitrofurantoin or sulfa agents) were
equally as likely as broad-spectrum agents to be accurate (P = 0.3). Choosing an
agent concordant with previous microbiologic data significantly increased the
chance of accuracy of therapy for MDR UTIs, even if the previous uropathogen was
a different species. Also, GU-directed or broad-spectrum therapy choices were
equally likely to be accurate. The accuracy of empiric therapy could be improved
by the use of these simple rules.
PMID- 26416860
TI - In Vitro Activity of Ceftaroline against Staphylococcus aureus Isolates Collected
in 2012 from Latin American Countries as Part of the AWARE Surveillance Program.
AB - The in vitro activities of ceftaroline and comparators, using broth
microdilution, were determined against 1,066 Staphylococcus aureus isolates from
hospitalized patients. Seventeen medical centers from Latin American countries
contributed isolates. Methicillin-resistant S. aureus (MRSA) percentages ranged
from 46% (Brazil) to 62% (Argentina). All methicillin-susceptible S. aureus
(MSSA) isolates were susceptible to ceftaroline. Ceftaroline activity against
MRSA varied with MIC90s of 0.5 (Venezuela) to 2 (Brazil, Chile, and Colombia)
MUg/ml, which was the highest MIC value. ST-5 was the most common sequence type.
PMID- 26416861
TI - In Vitro Activity of Miltefosine against Candida albicans under Planktonic and
Biofilm Growth Conditions and In Vivo Efficacy in a Murine Model of Oral
Candidiasis.
AB - The generation of a new antifungal against Candida albicans biofilms has become a
major priority, since biofilm formation by this opportunistic pathogenic fungus
is usually associated with an increased resistance to azole antifungal drugs and
treatment failures. Miltefosine is an alkyl phospholipid with promising
antifungal activity. Here, we report that, when tested under planktonic
conditions, miltefosine displays potent in vitro activity against multiple
fluconazole-susceptible and -resistant C. albicans clinical isolates, including
isolates overexpressing efflux pumps and/or with well-characterized Erg11
mutations. Moreover, miltefosine inhibits C. albicans biofilm formation and
displays activity against preformed biofilms. Serial passage experiments
confirmed that miltefosine has a reduced potential to elicit resistance, and
screening of a library of C. albicans transcription factor mutants provided
additional insight into the activity of miltefosine against C. albicans growing
under planktonic and biofilm conditions. Finally, we demonstrate the in vivo
efficacy of topical treatment with miltefosine in the murine model of
oropharyngeal candidiasis. Overall, our results confirm the potential of
miltefosine as a promising antifungal drug candidate, in particular for the
treatment of azole-resistant and biofilm-associated superficial candidiasis.
PMID- 26416862
TI - Cell Wall Recycling-Linked Coregulation of AmpC and PenB beta-Lactamases through
ampD Mutations in Burkholderia cenocepacia.
AB - In many Gram-negative pathogens, mutations in the key cell wall-recycling enzyme
AmpD (N-acetyl-anhydromuramyl-L-alanine amidase) affect the activity of the
regulator AmpR, which leads to the expression of AmpC beta-lactamase, conferring
resistance to expanded-spectrum cephalosporin antibiotics. Burkholderia cepacia
complex (Bcc) species also have these Amp homologs; however, the regulatory
circuitry and the nature of causal ampD mutations remain to be explored. A total
of 92 ampD mutants were obtained, representing four types of mutations: single
nucleotide substitution (causing an amino acid substitution or antitermination of
the enzyme), duplication, deletion, and IS element insertion. Duplication, which
can go through reversion, was the most frequent type. Intriguingly, mutations in
ampD led to the induction of two beta-lactamases, AmpC and PenB. Coregulation of
AmpC and PenB in B. cenocepacia, and likely also in many Bcc species with the
same gene organization, poses a serious threat to human health. This resistance
mechanism is of evolutionary optimization in that ampD is highly prone to
mutations allowing rapid response to antibiotic challenge, and many of the
mutations are reversible in order to resume cell wall recycling when the
antibiotic challenge is relieved.
PMID- 26416863
TI - High Efficacy of Finafloxacin on Helicobacter pylori Isolates at pH 5.0 Compared
with That of Other Fluoroquinolones.
AB - Finafloxacin is a novel fluoroquinolone with improved antimicrobial efficacy,
especially in an acidic environment. The efficacy of finafloxacin for the
inhibition of Helicobacter pylori infection was compared with the efficacies of
levofloxacin and moxifloxacin at neutral and acidic pH. The impacts of gyrA point
mutation on the efficacy of those three fluoroquinolones were also investigated.
A total of 128 clinical H. pylori strains were utilized. MICs of levofloxacin,
moxifloxacin, and finafloxacin were determined at pH 5.0 and pH 7.0 by the agar
dilution method. The impact of gyrA point mutations that are responsible for
fluoroquinolone resistance was analyzed; the results showed 50 strains with an
Asn-87 point mutation, 48 strains with an Asp-91 point mutation, and the
remaining 30 strains with no gyrA mutations. The use of finafloxacin led to MIC
values at pH 5.0 that were lower than the values seen at pH 7.0 for 112 strains
(112/128, 87.5%), and this proportion was higher than that seen with moxifloxacin
(21/128, 16.4%, P < 0.001). Finafloxacin also demonstrated a rate of
susceptibility (MIC, <1 MUg/ml) (37.5%, 48/128) at pH 5.0 that was higher than
that seen with moxifloxacin (2.3%, 3/128) (P < 0.001). The trends were similar
regardless of which of the Asn-87, Asp-91, and A2143 point mutations were
present. In conclusion, the superior antimicrobial efficacy of finafloxacin
against H. pylori in an acidic environment suggests the possible use of
finafloxacin for treatment of H. pylori infection, as has been proposed by its
developer, Merlion Pharma.
PMID- 26416864
TI - The Pathogen-Derived Aminoglycoside Resistance 16S rRNA Methyltransferase NpmA
Possesses Dual m1A1408/m1G1408 Specificity.
AB - Chemical modification of 16S rRNA can confer exceptionally high-level resistance
to a diverse set of aminoglycoside antibiotics. Here, we show that the pathogen
derived enzyme NpmA possesses dual m(1)A1408/m(1)G1408 activity, an unexpected
property apparently unique among the known aminoglycoside resistance 16S rRNA
(m(1)A1408) methyltransferases. Although the biological significance of this
activity remains to be determined, such mechanistic variation in enzymes acquired
by pathogens has significant implications for development of inhibitors of these
emerging resistance determinants.
PMID- 26416865
TI - K13-Propeller Polymorphisms in Plasmodium falciparum Isolates from Patients in
Mayotte in 2013 and 2014.
AB - Plasmodium falciparum isolates were collected from 29 malaria patients treated
with artemether-lumefantrine in Mayotte in 2013 and 2014. Twenty-four cases (83%)
consisted of imported malaria. Seventeen percent of the isolates presented
mutations in one of the six K13-propeller blades (N490H, F495L, N554H/K, and
E596G). A total of 23.8% of the isolates from the Union of Comoros showed K13
propeller polymorphisms. Three of the 18 isolates (16.7%) from Grande Comore
showed polymorphisms (N490H, N554K, and E596G).
PMID- 26416866
TI - Fluoroquinolone Impact on Nasal Methicillin-Resistant and Methicillin-Sensitive
Staphylococcus aureus Colonization Durations in Neurologic Long-Term-Care
Facilities.
AB - Staphylococcus aureus nasal carriage is a risk factor for subsequent infection.
Estimates of colonization duration vary widely among studies, and factors
influencing the time to loss of colonization, especially the impact of
antibiotics, remain unclear. We conducted a prospective study on patients naive
for S. aureus colonization in 4 French long-term-care facilities. Data on nasal
colonization status and potential factors for loss of colonization were collected
weekly. We estimated methicillin-resistant S. aureus (MRSA) and methicillin
sensitive S. aureus (MSSA) colonization durations using the Kaplan-Meier method
and investigated factors for loss of colonization using shared-frailty Cox
proportional hazards models. A total of 285 S. aureus colonization episodes were
identified in 149 patients. The median time to loss of MRSA or MSSA colonization
was 3 weeks (95% confidence interval, 2 to 8 weeks) or 2 weeks (95% confidence
interval, 2 to 3 weeks), respectively. In multivariable analyses, the methicillin
resistance phenotype was not associated with S. aureus colonization duration (P =
0.21); the use of fluoroquinolones (hazard ratio, 3.37; 95% confidence interval,
1.31 to 8.71) and having a wound positive for a nonnasal strain (hazard ratio,
2.17; 95% confidence interval, 1.15 to 4.07) were associated with earlier loss of
MSSA colonization, while no factor was associated with loss of MRSA colonization.
These results suggest that the methicillin resistance phenotype does not
influence the S. aureus colonization duration and that fluoroquinolones are
associated with loss of MSSA colonization but not with loss of MRSA colonization.
PMID- 26416868
TI - Evaluation of the Rapidec Carba NP Test Kit for Detection of Carbapenemase
Producing Gram-Negative Bacteria.
AB - Recently, bioMerieux, France, introduced the Rapidec Carba NP test kit for rapid
detection of carbapenemase-producing Gram-negative bacteria. This kit was
evaluated in this study, and we report sensitivity, specificity, and positive and
negative predictive values of 92.6%, 96.2%, 95.83%, and 92.6%, respectively. The
test was easy to perform and interpret and relatively inexpensive ($5/Rs 300 per
test) and provides a practical solution for early detection of carbapenemase
producing, multidrug-resistant Gram-negative bacteria.
PMID- 26416867
TI - Fitness Cost of Rifampin Resistance in Neisseria meningitidis: In Vitro Study of
Mechanisms Associated with rpoB H553Y Mutation.
AB - Rifampin chemoprophylaxis against Neisseria meningitidis infections led to the
onset of rifampin resistance in clinical isolates harboring point mutations in
the rpoB gene, coding for the RNA polymerase beta chain. These resistant strains
are rare in medical practice, suggesting their decreased fitness in the human
host. In this study, we isolated rifampin-resistant rpoB mutants from
hypervirulent serogroup C strain 93/4286 and analyzed their different properties,
including the ability to grow/survive in different culture media and in
differentiated THP-1 human monocytes and to compete with the wild-type strain in
vitro. Our results demonstrate that different rpoB mutations (H553Y, H553R, and
S549F) may have different effects, ranging from low- to high-cost effects, on
bacterial fitness in vitro. Moreover, we found that the S549F mutation confers
temperature sensitivity, possibly explaining why it is observed very rarely in
clinical isolates. Comparative high-throughput RNA sequencing analysis of
bacteria grown in chemically defined medium demonstrated that the low-cost H553Y
substitution resulted in global transcriptional changes that functionally mimic
the stringent response. Interestingly, many virulence-associated genes, including
those coding for meningococcal type IV pili, porin A, adhesins/invasins, IgA
protease, two-partner secretion system HrpA/HrpB, enzymes involved in resistance
to oxidative injury, lipooligosaccharide sialylation, and capsular polysaccharide
biosynthesis, were downregulated in the H553Y mutant compared to their level of
expression in the wild-type strain. These data might account for the reduced
capacity of this mutant to grow/survive in differentiated THP-1 cells and explain
the rarity of H553Y mutants among clinical isolates.
PMID- 26416869
TI - In Vitro Activities of Primaquine-Schizonticide Combinations on Asexual Blood
Stages and Gametocytes of Plasmodium falciparum.
AB - Currently, the World Health Organization recommends addition of a 0.25-mg base/kg
single dose of primaquine (PQ) to artemisinin combination therapies (ACTs) for
Plasmodium falciparum malaria as a gametocytocidal agent for reducing
transmission. Here, we investigated the potential interactions of PQ with the
long-lasting components of the ACT drugs for eliminating the asexual blood stages
and gametocytes of in vitro-cultured P. falciparum strains. Using the SYBR green
I assay for asexual parasites and a flow cytometry-based assay for gametocytes,
we determined the interactions of PQ with the schizonticides chloroquine,
mefloquine, piperaquine, lumefantrine, and naphthoquine. With the sums of
fractional inhibitory concentrations and isobolograms, we were able to determine
mostly synergistic interactions for the various PQ and schizonticide combinations
on the blood stages of P. falciparum laboratory strains. The synergism in
inhibiting asexual stages and gametocytes was highly evident with PQ
naphthoquine, whereas synergism was moderate for the PQ-piperaquine, PQ
chloroquine, and PQ-mefloquine combinations. We have detected potentially
antagonistic interactions between PQ and lumefantrine under certain drug
combination ratios, suggesting that precautions might be needed when PQ is added
as the gametocytocide to the artemether-lumefantrine ACT (Coartem).
PMID- 26416870
TI - Effects of Antiviral Drugs on Organic Anion Transport in Human Placental BeWo
Cells.
AB - Placental drug transfer is important for achieving better pharmacotherapy in
pregnant women and in fetuses. In the present study, we examined the effects of
anti-hepatitis C virus (HCV) and anti-HIV drugs on organic anion transport in
human placental BeWo cells. The cellular uptake of two fluorescence organic
anions, 8-(2-[fluoresceinyl]aminoethylthio)adenosine-3',5'-cyclic monophosphate
(8-FcAMP) and fluorescein, was temperature and concentration dependent. The
Michaelis constant (Km) and the maximum uptake rate (Vmax) for 8-FcAMP transport
in BeWo cells were estimated to be 6.45 +/- 0.75 MUM and 25.55 +/- 5.93 pmol/mg
protein/10 min, respectively. The Km and Vmax values for fluorescein uptake were
estimated to be 31.2 +/- 11.8 MUM and 510.9 +/- 90.6 pmol/mg protein/10 min,
respectively. Several known substrates of organic anion transporters in human
placenta, including atorvastatin, glibenclamide, estrone-3-sulfate, and rifampin,
inhibited cellular uptake of 8-FcAMP and fluorescein in BeWo cells. Transport of
8-FcAMP and fluorescein was inhibited by the antiviral drugs boceprevir,
telaprevir, elvitegravir, and maraviroc. These findings suggest that some
antiviral drugs are sufficiently potent to influence placental drug transfer and
cause drug-drug interactions.
PMID- 26416871
TI - Impact of Hydroxychloroquine-Loaded Polyurethane Intravaginal Rings on
Lactobacilli.
AB - The use of polymeric devices for controlled sustained delivery of drugs is a
promising approach for the prevention of HIV-1 infection. Unfortunately, certain
microbicides, when topically applied vaginally, may be cytotoxic to vaginal
epithelial cells and the protective microflora present within the female genital
tract. In this study, we evaluated the impact of hydroxychloroquine (HCQ)-loaded,
reservoir-type, polyurethane intravaginal rings (IVRs) on the growth of
Lactobacillus crispatus and Lactobacillus jensenii and on the viability of
vaginal and ectocervical epithelial cells. The IVRs were fabricated using hot
melt injection molding and were capable of providing controlled release of HCQ
for 24 days, with mean daily release rates of 17.01 +/- 3.6 MUg/ml in sodium
acetate buffer (pH 4) and 29.45 +/- 4.84 MUg/ml in MRS broth (pH 6.2). Drug-free
IVRs and the released HCQ had no significant effects on bacterial growth or the
viability of vaginal or ectocervical epithelial cells. Furthermore, there was no
significant impact on the integrity of vaginal epithelial cell monolayers, in
comparison with controls, as measured by transepithelial electrical resistance.
Overall, this is the first study to evaluate the effects of HCQ-loaded IVRs on
the growth of vaginal flora and the integrity of vaginal epithelial cell
monolayers.
PMID- 26416872
TI - Novel Type XII Staphylococcal Cassette Chromosome mec Harboring a New Cassette
Chromosome Recombinase, CcrC2.
AB - Excision and integration of staphylococcal cassette chromosome mec (SCCmec) are
mediated by cassette chromosome recombinases (Ccr), which play a crucial role in
the worldwide spread of methicillin resistance in staphylococci. We report a
novel ccr gene, ccrC2, in the SCCmec of a Staphylococcus aureus isolate, BA01611,
which showed 62.6% to 69.4% sequence identities to all published ccrC1 sequences.
A further survey found that the ccrC2 gene was mainly located among coagulase
negative staphylococci (CoNS) and could be found in staphylococcal isolates from
China, the United States, France, and Germany. The ccr gene complex harboring the
ccrC2 gene was designated a type 9 complex, and the SCCmec of BA01611 was
considered a novel type and was designated type XII (9C2). This novel SCCmec
element in BA01611 was flanked by a pseudo-SCC element (PsiSCCBA01611) carrying a
truncated ccrA1 gene. Both individual SCC elements and a composite SCC were
excised from the chromosome based on detection of extrachromosomal circular
intermediates. We advocate inclusion of the ccrC2 gene and type 9 ccr gene
complex during revision of the SCCmec typing method.
PMID- 26416873
TI - Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter
baumannii Strains Displaying Different Antibiotic Resistance Phenotypes.
AB - A paucity of effective, currently available antibiotics and a lull in antibiotic
development pose significant challenges for treatment of patients with multidrug
resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic
strategies must be evaluated to meet the demands of treatment of these often life
threatening infections. Accordingly, we examined the antibiotic activity of
gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains,
including nonmilitary and military strains and strains representing different
clonal lineages and isolates classified as susceptible or MDR. Susceptibility
testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when
cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 MUg/ml. This
concentration significantly reduced bacterial viability, while 40 MUg/ml killed
all cells of the A. baumannii ATCC 19606(T) and ACICU MDR isolate after 24-h
incubation. Recovery of ATCC 19606(T) and ACICU strains from infected A549 human
alveolar epithelial monolayers was also decreased when the medium was
supplemented with Ga-PPIX, particularly at a 40-MUg/ml concentration. Similarly,
the coinjection of bacteria with Ga-PPIX increased the survival of Galleria
mellonella larvae infected with ATCC 19606(T) or ACICU. Ga-PPIX was cytotoxic
only when monolayers or larvae were exposed to concentrations 16-fold and 1,250
fold higher than those showing antibacterial activity, respectively. These
results indicate that Ga-PPIX could be a viable therapeutic option for treatment
of recalcitrant A. baumannii infections regardless of the resistance phenotype,
clone lineage, time and site of isolation of strains causing these infections and
their iron uptake phenotypes or the iron content of the media.
PMID- 26416874
TI - Validation and Application of a Liquid Chromatography-Tandem Mass Spectrometry
Method To Determine the Concentrations of Sofosbuvir Anabolites in Cells.
AB - Sofosbuvir (SOF) is a highly efficacious and well-tolerated uridine nucleotide
analog that inhibits the hepatitis C virus (HCV) NS5B polymerase enzyme. SOF is
administered as a prodrug, which undergoes intracellular phosphorylation by host
enzymes to a monophosphate, diphosphate, and finally a pharmacologically active
triphosphate. In order to fully understand the clinical pharmacology of SOF,
there is a great need to determine the intracellular phosphate concentrations of
the drug. We describe the validation and utilization of a method to characterize
SOF's disposition into various in vivo cell types, including hepatocytes,
peripheral blood mononuclear cells (PBMC), and red blood cells (RBC). Standard
bioanalytical validation criteria were applied to lysed cellular matrices, with a
validated linear range of 50 to 50,000 fmol/sample for each phosphate moiety. The
assay was utilized to collect the first data demonstrating concentrations of
phosphorylated anabolites formed in PBMC, hepatocytes, and RBC in vivo during SOF
therapy. Median concentrations in PBMC were 220 (range, 51.5 to 846), 70.2
(range, 25.8 to 275), and 859 (range, 54.5 to 6,756) fmol/10(6) cells in the
monophosphate, diphosphate, and triphosphate fractions, respectively. In
contrast, RBC triphosphate concentrations were much lower than those of PBMC, as
the median concentration was 2.91 (range, 1.14 to 10.4) fmol/10(6) cells. The
PBMC triphosphate half-life was estimated at 26 h using noncompartmental
approaches, while nonlinear mixed-effect modeling was used to estimate a 69 h
half-life for this moiety in RBC. The validated method and the data it generates
provide novel insight into the cellular disposition of SOF and its phosphorylated
anabolites in vivo.
PMID- 26416875
TI - Impact of 2-Weeks Continuous Increase in Retrograde Shear Stress on Brachial
Artery Vasomotor Function in Young and Older Men.
AB - BACKGROUND: Although acute elevation in retrograde shear rate (SR) impairs
endothelial function, no previous study has explored the effect of prolonged
elevation of retrograde SR on conduit artery vascular function. We examined the
effect of 2-weeks elevation of retrograde SR on brachial artery endothelial
function in young and in older men. METHODS AND RESULTS: Thirteen healthy young
(23+/-2 years) and 13 older men (61+/-5 years) were instructed to continuously
wear a compression sleeve around the right forearm to chronically (2 weeks)
elevate brachial artery retrograde SR in 1 arm. We assessed SR, diameter, and
flow-mediated dilation in both the sleeve and contralateral control arms at
baseline and after 30 minutes and 2 weeks of continuous sleeve application. The
sleeve intervention increased retrograde SR after 30 minutes and 2 weeks in both
young and older men (P=0.03 and 0.001, respectively). In young men, brachial
artery flow-mediated dilation % was lower after 30 minutes and 2 weeks (P=0.004),
while resting artery diameter was reduced after 2 weeks (P=0.005). The
contralateral arm showed no change in retrograde SR or flow-mediated dilation %
(P=0.32 and 0.26, respectively), but a decrease in diameter (P=0.035). In older
men, flow-mediated dilation % and diameter did not change in either arm (all
P>0.05). CONCLUSIONS: Thirty-minute elevation in retrograde SR in young men
caused impaired endothelial function, while 2-week exposure to elevated levels of
retrograde SR was associated with a comparable decrease in endothelial function.
Interestingly, these vascular changes were not present in older men, suggesting
age-related vascular changes to elevation in retrograde SR.
PMID- 26416876
TI - Hemodynamic Correlates of Abnormal Aortic Root Dimension in an Adult Population:
The Strong Heart Study.
AB - BACKGROUND: We evaluated the relationship of aortic root dimension (ARD) with
flow output and both peripheral and central blood pressure, using multivariable
equations predicting ideal sex-specific ARD at a given age and body height.
METHODS AND RESULTS: We measured echocardiographic diastolic ARD at the sinuses
of Valsalva in 3160 adults (aged 42+/-16 years, 61% women) from the fourth
examination of the Strong Heart Study who were free of prevalent coronary heart
disease, and we compared measured data with the theoretical predicted value to
calculate a z score. Central blood pressure was estimated by applanation
tonometry of the radial artery in 2319 participants. ARD z scores were divided
into tertiles representing small, normal, and large ARD. Participants with large
ARD exhibited greater prevalence of central obesity and higher levels of
inflammatory markers and lipids (0.05
=75% likelihood of indicating CWD. Examples
include 318.2 Profound intellectual disabilities and 780.72 Functional
quadriplegia. CWDA sensitivity was 0.75 (95% confidence interval 0.63-0.84)
compared with parent report and 0.98 (0.95-0.99) compared with physician
assessment; its specificity was 0.86 (0.72-0.95) and 0.50 (0.41-0.59),
respectively. CONCLUSIONS: ICD-9-CM codes can be classified by their likelihood
of indicating CWD. CWDA triangulates well with parent report and physician
assessment of child disability status. CWDA is a new tool that can be used to
assess care quality for CWD.
PMID- 26416936
TI - Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized
Controlled Trial.
AB - OBJECTIVE: Compare effectiveness of maternal vitamin D3 supplementation with 6400
IU per day alone to maternal and infant supplementation with 400 IU per day.
METHODS: Exclusively lactating women living in Charleston, SC, or Rochester, NY,
at 4 to 6 weeks postpartum were randomized to either 400, 2400, or 6400 IU
vitamin D3/day for 6 months. Breastfeeding infants in 400 IU group received oral
400 IU vitamin D3/day; infants in 2400 and 6400 IU groups received 0 IU/day
(placebo). Vitamin D deficiency was defined as 25-hydroxy-vitamin D (25(OH)D) <50
nmol/L. 2400 IU group ended in 2009 as greater infant deficiency occurred.
Maternal serum vitamin D, 25(OH)D, calcium, and phosphorus concentrations and
urinary calcium/creatinine ratios were measured at baseline then monthly, and
infant blood parameters were measured at baseline and months 4 and 7. RESULTS: Of
the 334 mother-infant pairs in 400 IU and 6400 IU groups at enrollment, 216
(64.7%) were still breastfeeding at visit 1; 148 (44.3%) continued full
breastfeeding to 4 months and 95 (28.4%) to 7 months. Vitamin D deficiency in
breastfeeding infants was greatly affected by race. Compared with 400 IU vitamin
D3 per day, 6400 IU/day safely and significantly increased maternal vitamin D and
25(OH)D from baseline (P < .0001). Compared with breastfeeding infant 25(OH)D in
the 400 IU group receiving supplement, infants in the 6400 IU group whose mothers
only received supplement did not differ. CONCLUSIONS: Maternal vitamin D
supplementation with 6400 IU/day safely supplies breast milk with adequate
vitamin D to satisfy her nursing infant's requirement and offers an alternate
strategy to direct infant supplementation.
PMID- 26416939
TI - Preterm Infant Attendance at Health Supervision Visits.
AB - OBJECTIVES: To assess the adherence of premature infants with the American
Academy of Pediatrics health supervision visit schedule, factors affecting
adherence, and the association of adherence with preventive care. METHODS:
Retrospective cohort of all infants <=35 weeks' gestation, born 2005 to 2009,
receiving care at a 30-site primary care network for at least 24 months (n =
1854). Adherence was defined as having a health supervision visit within each
expected time period during the first 18 months of life. Logistic regression
identified sociodemographic and medical factors associated with nonadherence and
risk-adjusted association between nonadherence and outcomes. RESULTS: Only 43%
received all expected health supervision visits. Those with Medicaid insurance
(adjusted odds ratio [AOR] 0.46, 95% confidence interval [CI] 0.35-0.60), a visit
without insurance (AOR 0.46, 95% CI 0.32-0.67), chronic illness (AOR 0.7, 95% CI
0.51-0.97), and black race (AOR 0.7, 95% CI 0.50-0.98) were less adherent,
whereas provider continuity of care (AOR 2.89, 95% CI 1.92-4.37) and lower birth
weight (AOR 1.67, 95% CI 1.02-2.73) increased adherence. Infants <100% adherent
were less likely to be up to date with immunizations and receive recommended
preventive care. In nearly half of missed visit windows, no health supervision
visit was scheduled. CONCLUSIONS: Fewer than half of premature infants were fully
adherent with the preventive health schedule with associated gaps in health
monitoring and immunization delays. These data suggest the importance of health
supervision visits and the need to explore scheduling facilitators for those at
risk for nonadherence.
PMID- 26416940
TI - Chronic Pain Assessment Tools for Cerebral Palsy: A Systematic Review.
AB - BACKGROUND AND OBJECTIVE: Chronic pain in children with cerebral palsy (CP) is
underrecognized, leading to detriments in their physical, social, and mental well
being. Our objective was to identify, describe, and critique pediatric chronic
pain assessment tools and make recommendations for clinical use for children with
CP. Secondly, develop an evidence-informed toolbox to support clinicians in the
assessment of chronic pain in children with disabilities. METHODS: Ovid Medline,
Cumulative Index to Nursing and Allied Health Literature, and Embase databases
were systematically searched by using key terms "chronic pain" and "clinical
assessment tool" between January 2012 and July 2014. Tools from multiple
pediatric health conditions were explored contingent on inclusion criteria: (1)
children 1 to 18 years; (2) assessment focus on chronic pain; (3) psychometric
properties reported; (4) written in English between 1980 and 2014. Pediatric
chronic pain assessment tools were extracted and corresponding validation
articles were sought for review. Detailed tool descriptions were composed and
each tool underwent a formal critique of psychometric properties and clinical
utility. RESULTS: Of the retrieved 2652 articles, 250 articles met eligibility,
from which 52 chronic pain assessment tools were retrieved. A consensus among
interprofessional working group members determined 7 chronic pain interference
tools to be of importance. Not all tools have been validated with children with
CP nor is there 1 tool to meet the needs of all children experiencing chronic
pain. CONCLUSIONS: This study has systematically reviewed and recommended,
through expert consensus, valid and reliable chronic pain interference assessment
tools for children with disabilities.
PMID- 26416941
TI - Health Care Issues for Children and Adolescents in Foster Care and Kinship Care.
AB - Children and adolescents who enter foster care often do so with complicated and
serious medical, mental health, developmental, oral health, and psychosocial
problems rooted in their history of childhood trauma. Ideally, health care for
this population is provided in a pediatric medical home by physicians who are
familiar with the sequelae of childhood trauma and adversity. As youth with
special health care needs, children and adolescents in foster care require more
frequent monitoring of their health status, and pediatricians have a critical
role in ensuring the well-being of children in out-of-home care through the
provision of high-quality pediatric health services, health care coordination,
and advocacy on their behalves.
PMID- 26416942
TI - Intraurethral Lidocaine for Urethral Catheterization in Children: A Randomized
Controlled Trial.
AB - OBJECTIVES: To determine whether lidocaine is superior to nonanesthetic lubricant
(NAL) for relieving pain in children undergoing urethral catheterization (UC).
METHODS: Children 0 to 24 months requiring UC were randomized to NAL or topical
and intraurethral 2% lidocaine gel. Primary outcome was facial grimacing in the
pre to during drug administration and catheterization phases. Secondary outcome
was caregiver satisfaction by using a Visual Analog Scale. RESULTS: There were
133 participants (n = 68 lidocaine, n = 65 NAL). There were no significant
differences in mean (SD) scores during UC between lidocaine and NAL (86.4%
[121.5%] vs 85.2% [126.6%]), respectively (Delta [confidence interval (CI)] =
1.2 [-21.0 to 49.0], P = .4). There was a significantly greater difference in
mean (SD) scores during instillation of lidocaine versus NAL (61.8% [105.6%] vs
3.2% [84.9%]), respectively (Delta [CI] -58.6 [-95.0 to -32.0], P < .001). There
were no significant differences in mean (SD) parental satisfaction scores between
lidocaine and NAL (4.8 [3.2] vs 5.9 [2.9]), respectively (CI-0.1 to 2.2; P =
.06). In the subgroup analysis, age, gender, and positive urine culture did not
significantly influence between-group differences in facial grimacing.
CONCLUSIONS: Compared with NAL, topical and intraurethral lidocaine is not
associated with significant pain reduction during UC, but significantly greater
pain during instillation. Therefore, clinicians may consider using noninvasive
pain-reducing strategies for young children who require UC.
PMID- 26416944
TI - Is Intravenous Iron Supplementation Safe to Administer to Patients on
Hemodialysis with Active Infection--What Do We Know, and What More Do We Need to
Know?
PMID- 26416943
TI - Receipt of Intravenous Iron and Clinical Outcomes among Hemodialysis Patients
Hospitalized for Infection.
AB - BACKGROUND AND OBJECTIVES: Anemia guidelines for CKD recommend withholding
intravenous iron in the setting of active infection, although no data
specifically support this recommendation. This study aimed to examine the
association between intravenous iron and clinical outcomes among hemodialysis
patients hospitalized for infection. DESIGN, SETTING, PARTICIPANTS, &
MEASUREMENTS: This was a retrospective observational cohort study using data from
the US Renal Data System of 22,820 adult Medicare beneficiaries on in-center
hemodialysis who had received intravenous iron in the 14 days preceding their
first hospitalization for bacterial infection in 2010. In multivariable analyses,
the association between receipt of intravenous iron at any point from the day of
hospital admission to discharge and all-cause 30-day mortality, mortality in
2010, length of hospital stay, and readmission for infection or death within 30
days of discharge was evaluated. RESULTS: There were 2463 patients (10.8%) who
received intravenous iron at any point from the day of admission to discharge.
Receipt of intravenous iron was not associated with age, dialysis vintage, or
comorbidities. There were 2618 deaths within 30 days of admission and 6921 deaths
in 2010 (median follow-up 173 days; 25th and 75th percentiles, 78-271 days). The
median length of stay was 7 days (25th and 75th percentiles, 5-12 days). Receipt
of intravenous iron was not associated with higher 30-day mortality (odds ratio,
0.86; 95% confidence interval [95% CI], 0.74 to 1.00), higher mortality in 2010
(hazard ratio, 0.92; 95% CI, 0.85 to 1.00), longer mean length of stay (10.1 days
[95% CI, 9.7 to 10.5] versus 10.5 days [95% CI, 10.3 to 10.7]; P=0.05), or
readmission for infection or death within 30 days of discharge (odds ratio, 1.08;
95% CI, 0.96 to 1.22) compared with no receipt of intravenous iron. CONCLUSIONS:
This analysis does not support withholding intravenous iron upon admission for
bacterial infection in hemodialysis patients, although clinical trials are
required to make definitive recommendations.
PMID- 26416945
TI - The Role of Ethnic Variation and CKD.
PMID- 26416947
TI - Evaluation of the Hemodynamic Effects of Intravenous Amiodarone Formulations
During the Maintenance Phase Infusion.
AB - BACKGROUND: Two of the excipients in intravenous formulations of amiodarone,
polysorbate 80 and benzyl alcohol, have been shown to cause hypotension. A newer
formulation of amiodarone, which contains cyclodextrin, is devoid of these
excipients. OBJECTIVE: To evaluate the change in mean arterial pressure when
utilizing 2 intravenous amiodarone formulations. METHODS: This was a
retrospective cohort analysis conducted at an academic medical center. Patients
received intravenous amiodarone containing either polysorbate 80/benzyl alcohol
(control) or cyclodextrin (cyclodextrin). Patients received these formulations
based on a standard institutional protocol of 1 mg/min for 6 hours, followed by
0.5 mg/min for at least 18 hours or until discontinued by the provider. All data
were collected from the medical record and included changes in blood pressures,
time to lowest systolic blood pressure, concurrent antihypertensive use, and
number of patients requiring treatment for hypotension. RESULTS: A total of 160
patients (120 control, 40 cyclodextrin) were included. There was a statistically
significant difference in mean arterial pressure between the groups receiving the
control formulation of amiodarone compared with the cyclodextrin formulation
across the 24-hour maintenance phase infusion (P < 0.001). There was a
significant difference between formulations with regard to the change in mean
arterial pressure during the 0- to 6-hour and 12- to 18-hour time blocks. There
was a statistically significant difference in the number of patients receiving
fluid boluses for treatment of hypotension (P = 0.001). CONCLUSIONS: The
excipients in the formulation of intravenous amiodarone may have a significant
role in the hypotensive effects seen throughout the duration the maintenance
phase infusion.
PMID- 26416946
TI - Prevalence and Correlates of CKD in Hispanics/Latinos in the United States.
AB - BACKGROUND AND OBJECTIVES: The prevalence of ESRD among Hispanics/Latinos is 2
fold higher than in non-Hispanic whites. However, little is known about the
prevalence of earlier stages of CKD among Hispanics/Latinos. This study estimated
the prevalence of CKD in US Hispanics/Latinos. DESIGN, SETTING, PARTICIPANTS, &
MEASUREMENTS: This was a cross-sectional study of 15,161 US Hispanic/Latino
adults of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South
American backgrounds enrolled in the multicenter, prospective, population-based
Hispanic Community Health Study/Study of Latinos (HCHS/SOL). In addition, the
prevalence of CKD in Hispanics/Latinos was compared with other racial/ethnic
groups in the 2007-2010 National Health and Nutrition Examination Survey
(NHANES). Prevalent CKD was defined as an eGFR <60 ml/min per 1.73 m(2)
(estimated with the 2012 Chronic Kidney Disease Epidemiology Collaboration eGFR
creatinine-cystatin C equation) or albuminuria based on sex-specific cut points
determined at a single point in time. RESULTS: The overall prevalence of CKD
among Hispanics/Latinos was 13.7%. Among women, the prevalence of CKD was 13.0%,
and it was lowest in persons with South American background (7.4%) and highest
(16.6%) in persons with Puerto Rican background. In men, the prevalence of CKD
was 15.3%, and it was lowest (11.2%) in persons with South American background
and highest in those who identified their Hispanic background as "other" (16.0%).
The overall prevalence of CKD was similar in HCHS/SOL compared with non-Hispanic
whites in NHANES. However, prevalence was higher in HCHS/SOL men and lower in
HCHS/SOL women versus NHANES non-Hispanic whites. Low income, diabetes mellitus,
hypertension, and cardiovascular disease were each significantly associated with
higher risk of CKD. CONCLUSIONS: Among US Hispanic/Latino adults, there was
significant variation in CKD prevalence among Hispanic/Latino background groups,
and CKD was associated with established cardiovascular risk factors.
PMID- 26416948
TI - Predictors of Pregnancy in Female Veterans Receiving a Hormonal Contraceptive
Pill, Patch, or Ring.
AB - BACKGROUND: Pregnancy rates in veterans are an understudied phenomenon.
OBJECTIVE: The objective of this study was to identify predictors of pregnancy
within 1 year of starting hormonal contraception among female veterans. METHODS:
This was a retrospective, cohort study of female veterans from Veterans Affairs
facilities within Southern California and Nevada, who newly started hormonal
contraception (pill, patch, or ring only) between October 2008 and September
2012. Pregnancy was defined as any event corresponding to a pregnant state using
ICD-9 codes. Patients were followed for 1 year post-initiation. Multivariate
logistic regression analysis was performed. RESULTS: The final analysis included
a total of 2166 patients. Approximately 5.9% (n = 127) of patients became
pregnant during follow-up. Increased odds of pregnancy were associated with the
following: mental health disease (odds ratio [OR] 1.69, 95% confidence interval
[CI] 1.15-2.58), lowest socioeconomic quintile (OR 1.50, 95% CI 1.05-2.09), and
Christian faith (OR 1.69, 95% CI 1.31-2.41). Age groups 25 to 34 years (OR 0.55,
95% CI 0.38-0.92] and 35 to 44 years (OR 0.32, 95% CI 0.06-0.64) were both
associated with decreased odds of pregnancy versus age group 18 to 24 years.
CONCLUSION: This study successfully identified several predictors of pregnancy in
female veterans starting a pill, patch, or ring form of hormonal contraception.
Female veterans in the lowest socioeconomic quintile, aged 18 to 24 years,
diagnosed with a mental health disorder, and of Christian faith were found to be
at significantly higher odds of a pregnancy. Identification of these at-risk
populations may help clinicians and policy makers choose strategies to identify
which patients could benefit the most from more effective long-acting reversible
contraception therapy.
PMID- 26416950
TI - Evaluation of Statin Prescribing for Secondary Prevention in Primary Care
Following New Guideline Recommendations.
AB - BACKGROUND: The American College of Cardiology/American Heart Association
(ACC/AHA) Guideline on the Treatment of Blood Cholesterol recommends high
intensity statin therapy for most patients with established atherosclerotic
cardiovascular disease (ASCVD) versus previously recommended low-density
lipoprotein cholesterol targets. The impact of the ACC/AHA guidelines on
prescribing patterns in primary care is uncertain. OBJECTIVE: To describe the
prescribing habits of statin therapy in primary care patients with ASCVD before
and after the ACC/AHA guidelines were published. METHODS: This retrospective
observational study evaluated patients with ASCVD who were seen in at least 1 of
8 primary care clinics in the University of Colorado Health system. It received
expedited approval by the Colorado Multiple Institutional Review Board. The
primary outcome measure was the proportion of patients with established ASCVD
prescribed high-intensity statin therapy within 1 year before or after guideline
release. RESULTS: In total, 220 patients were included in the analysis with 110
in the before and 110 in the after cohort. For the primary outcome analysis, the
rate of high-intensity statin utilization in the before versus after groups was
significantly greater (25.5% vs 41.8%, P = 0.01). For ages 76 to 89 years, 36 of
37 and 29 of 30 patients in the before and after groups were receiving moderate-
to high-intensity statin therapy (97.3% vs 96.7%, P = 0.99). Subgroup analysis in
the after cohort for all ages showed no change in statin therapy for 77% of
patients. CONCLUSIONS: High-intensity statin prescribing increased in patients
with ASCVD after release of the ACC/AHA cholesterol guidelines. Our data indicate
that national evidence-based guidelines may influence clinical practice in very
high risk patients.
PMID- 26416949
TI - Off-Label Use of Agents for Management of Serious or Life-threatening Angiotensin
Converting Enzyme Inhibitor-Induced Angioedema.
AB - OBJECTIVE: To evaluate the place in therapy of fresh frozen plasma (FFP), C1
esterase concentrate (C1-INH), ecallantide, and icatibant in the management of
angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-IA). DATA
SOURCES: A literature search was performed using PubMed (1946 through August
2015) and Embase (<1966 through August 2015). References from identified articles
were reviewed. STUDY SELECTION AND DATA EXTRACTION: Consensus papers, practice
guidelines, case reports/series, clinical trials, and meeting abstracts published
in English and involving humans were included. DATA SYNTHESIS: No medications are
currently Food and Drug Administration-approved for managing ACEI-IA. Emerging
evidence suggests that FFP and medications approved for management of acute
attacks of hereditary angioedema, another bradykinin-mediated event, may be
effective for use in ACEI-IA. Positive efficacy results were reported with FFP
and C1-INH while mixed results have been seen with ecallantide. Off-label
icatibant has the most evidence supporting its use in ACEI-IA with rapid symptom
resolution (10 minutes to 6 hours) and avoidance of intubation and tracheotomy in
several cases. These agents were well-tolerated in ACEI-IA. CONCLUSION: ACEI-IA
is typically a self-limiting event. First-line therapies include ACEI
discontinuation, observation, and supportive medications (eg, corticosteroids,
antihistamines, and epinephrine). Symptom progression can be life-threatening and
may require interventions such as tracheotomy and intubation. Off-label use of
FFP and medications approved for hereditary angioedema have resulted in rapid
resolution of symptoms and avoidance of intubation. Among these agents, icatibant
has the most supporting evidence and has been incorporated into practice
guidelines and algorithms as a second-line agent for serious life-threatening ACE
IA.
PMID- 26416951
TI - Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and
Dextrose for Hyperkalemia.
AB - BACKGROUND: Hyperkalemia is a potentially life-threatening condition that is
common in kidney disease patients. Insulin is used to treat hyperkalemia, but may
cause hypoglycemia, especially in kidney disease when insulin may be metabolized
more slowly. OBJECTIVE: We compared the rates of hypoglycemia in patients with
low estimated glomerular filtration rate (eGFR) using high versus low doses of
insulin for hyperkalemia to determine if lower doses of insulin would decrease
the incidence of hypoglycemia. METHODS: This was a retrospective study of
hospitalized patients receiving intravenous insulin for hyperkalemia during a 6
month period. Patients with low eGFR were analyzed based on how much insulin they
received: high dose (10 units, n = 78) versus low dose (5 units, n = 71).
Postdose nadir blood glucose values were examined for up to 8 hours after the
dose. The percentage of hypoglycemia (blood glucose <=70 mg/dl) and a subset of
severe hypoglycemia (blood glucose <50 mg/dl) were then reported for each dose
group. RESULTS: A total of 149 doses were identified in patients with low eGFR.
The rates of hypoglycemia were 16.7% and 19.7% (P = 0.79), respectively, among
high-dose (n = 78) and low-dose (n = 71) groups. Rates of severe hypoglycemia
were 8.9% and 7.0%, respectively (P = 0.90). More than 28% of hypoglycemic
episodes with high doses occurred after 4 hours (median = 2.5 hours) compared
with 14.3% with low doses (median = 2.38 hours). CONCLUSION: There was no
difference in the rate of hypoglycemia or severe hypoglycemia between high or low
doses of insulin in patients with low eGFR. We recommend monitoring up to 6 hours
after insulin use in hyperkalemia.
PMID- 26416953
TI - Correction.
PMID- 26416952
TI - Navigating the plant cell: intracellular transport logistics in the green
kingdom.
AB - Intracellular transport in plant cells occurs on microtubular and actin arrays.
Cytoplasmic streaming, the rapid motion of plant cell organelles, is mostly
driven by an actin-myosin mechanism, whereas specialized functions, such as the
transport of large cargo or the assembly of a new cell wall during cell division,
are performed by the microtubules. Different modes of transport are used, fast
and slow, to either haul cargo over long distances or ascertain high-precision
targeting, respectively. Various forms of the actin-specific motor protein myosin
XI exist in plant cells and might be involved in different cellular functions.
PMID- 26416954
TI - What triggers migraine aura?
PMID- 26416955
TI - Shemamruthaa, a Herbal Formulation Induces Apoptosis in Breast Cancer Cells and
Inhibits Tumor Progression in Rats.
AB - Phytochemicals present in plants are more effective than their individual
constituents in preventing cancer through synergetic effects. From this
perspective, Shemamruthaa, a herbal formulation was evaluated with a view to
potentiate more intense anticancer property. This study investigates the
anticancer activity of Shemamruthaa in breast cancer (MDA-MB 231) cell lines and
its cancer therapeutic potential in 7,12-dimethylbenz[a]anthracene induced breast
cancer rats. Results of MTT, trypan blue, and apoptotic marker assays suggested
that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration-
and time-dependent manner. Oral administration of Shemamruthaa effectively
suppressed the tumor progression as evidenced by decrease in tumor volume and
modulation of oxidant-antioxidant status and resulted in extended life span. Gas
chromatography-mass spectrometry and high-performance liquid chromatography
analysis of Shemamruthaa revealed the presence of pyrogallol, 5
hydrxoymethylfurfural, trilinolein, and flavonoids. Finally, we show that
Shemamruthaa contains potential anticancer agents acting either singly or in
combination against breast cancer cell proliferation.
PMID- 26416956
TI - Nihal Altan-Bonnet: Tracking viruses that hijack membranes.
PMID- 26416957
TI - When cell biology meets theory.
AB - Cell biologists now have tools and knowledge to generate useful quantitative
data. But how can we make sense of these data, and are we measuring the correct
parameters? Moreover, how can we test hypotheses quantitatively? To answer these
questions, the theory of physics is required and is essential to the future of
quantitative cell biology.
PMID- 26416958
TI - Sam37 is crucial for formation of the mitochondrial TOM-SAM supercomplex, thereby
promoting beta-barrel biogenesis.
AB - Biogenesis of mitochondrial beta-barrel proteins requires two preprotein
translocases, the general translocase of the outer membrane (TOM) and the sorting
and assembly machinery (SAM). TOM and SAM form a supercomplex that promotes
transfer of beta-barrel precursors. The SAM core complex contains the channel
protein Sam50, which cooperates with Sam35 in precursor recognition, and the
peripheral membrane protein Sam37. The molecular function of Sam37 has been
unknown. We report that Sam37 is crucial for formation of the TOM-SAM
supercomplex. Sam37 interacts with the receptor domain of Tom22 on the cytosolic
side of the mitochondrial outer membrane and links TOM and SAM complexes. Sam37
thus promotes efficient transfer of beta-barrel precursors to the SAM complex. We
conclude that Sam37 functions as a coupling factor of the translocase
supercomplex of the mitochondrial outer membrane.
PMID- 26416960
TI - Reevaluating alphaE-catenin monomer and homodimer functions by characterizing E
cadherin/alphaE-catenin chimeras.
AB - As part of the E-cadherin-beta-catenin-alphaE-catenin complex (CCC), mammalian
alphaE-catenin binds F-actin weakly in the absence of force, whereas cytosolic
alphaE-catenin forms a homodimer that interacts more strongly with F-actin. It
has been concluded that cytosolic alphaE-catenin homodimer is not important for
intercellular adhesion because E-cadherin/alphaE-catenin chimeras thought to
mimic the CCC are sufficient to induce cell-cell adhesion. We show that, unlike
alphaE-catenin in the CCC, these chimeras homodimerize, bind F-actin strongly,
and inhibit the Arp2/3 complex, all of which are properties of the alphaE-catenin
homodimer. To more accurately mimic the junctional CCC, we designed a
constitutively monomeric chimera, and show that E-cadherin-dependent cell
adhesion is weaker in cells expressing this chimera compared with cells in which
alphaE-catenin homodimers are present. Our results demonstrate that E
cadherin/alphaE-catenin chimeras used previously do not mimic alphaE-catenin in
the native CCC, and imply that both CCC-bound monomer and cytosolic homodimer
alphaE-catenin are required for strong cell-cell adhesion.
PMID- 26416959
TI - ATP8B1-mediated spatial organization of Cdc42 signaling maintains singularity
during enterocyte polarization.
AB - During yeast cell polarization localization of the small GTPase, cell division
control protein 42 homologue (Cdc42) is clustered to ensure the formation of a
single bud. Here we show that the disease-associated flippase ATPase class I type
8b member 1 (ATP8B1) enables Cdc42 clustering during enterocyte polarization.
Loss of this regulation results in increased apical membrane size with scattered
apical recycling endosomes and permits the formation of more than one apical
domain, resembling the singularity defect observed in yeast. Mechanistically, we
show that to become apically clustered, Cdc42 requires the interaction between
its polybasic region and negatively charged membrane lipids provided by ATP8B1.
Disturbing this interaction, either by ATP8B1 depletion or by introduction of a
Cdc42 mutant defective in lipid binding, increases Cdc42 mobility and results in
apical membrane enlargement. Re-establishing Cdc42 clustering, by tethering it to
the apical membrane or lowering its diffusion, restores normal apical membrane
size in ATP8B1-depleted cells. We therefore conclude that singularity regulation
by Cdc42 is conserved between yeast and human and that this regulation is
required to maintain healthy tissue architecture.
PMID- 26416961
TI - Muller glia provide essential tensile strength to the developing retina.
AB - To investigate the cellular basis of tissue integrity in a vertebrate central
nervous system (CNS) tissue, we eliminated Muller glial cells (MG) from the
zebrafish retina. For well over a century, glial cells have been ascribed a
mechanical role in the support of neural tissues, yet this idea has not been
specifically tested in vivo. We report here that retinas devoid of MG rip apart,
a defect known as retinoschisis. Using atomic force microscopy, we show that
retinas without MG have decreased resistance to tensile stress and are softer
than controls. Laser ablation of MG processes showed that these cells are under
tension in the tissue. Thus, we propose that MG act like springs that hold the
neural retina together, finally confirming an active mechanical role of glial
cells in the CNS.
PMID- 26416962
TI - PAR-4 and anillin regulate myosin to coordinate spindle and furrow position
during asymmetric division.
AB - During asymmetric cell division, the mitotic spindle and polarized myosin can
both determine the position of the cytokinetic furrow. However, how cells
coordinate signals from the spindle and myosin to ensure that cleavage occurs
through the spindle midzone is unknown. Here, we identify a novel pathway that is
essential to inhibit myosin and coordinate furrow and spindle positions during
asymmetric division. In Caenorhabditis elegans one-cell embryos, myosin localizes
at the anterior cortex whereas the mitotic spindle localizes toward the
posterior. We find that PAR-4/LKB1 impinges on myosin via two pathways, an
anillin-dependent pathway that also responds to the cullin CUL-5 and an anillin
independent pathway involving the kinase PIG-1/MELK. In the absence of both PIG
1/MELK and the anillin ANI-1, myosin accumulates at the anterior cortex and
induces a strong displacement of the furrow toward the anterior, which can lead
to DNA segregation defects. Regulation of asymmetrically localized myosin is thus
critical to ensure that furrow and spindle midzone positions coincide throughout
cytokinesis.
PMID- 26416963
TI - PDK2-mediated alternative splicing switches Bnip3 from cell death to cell
survival.
AB - Herein we describe a novel survival pathway that operationally links alternative
pre-mRNA splicing of the hypoxia-inducible death protein Bcl-2 19-kD interacting
protein 3 (Bnip3) to the unique glycolytic phenotype in cancer cells. While a
full-length Bnip3 protein (Bnip3FL) encoded by exons 1-6 was expressed as an
isoform in normal cells and promoted cell death, a truncated spliced variant of
Bnip3 mRNA deleted for exon 3 (Bnip3Deltaex3) was preferentially expressed in
several human adenocarcinomas and promoted survival. Reciprocal inhibition of the
Bnip3Deltaex3/Bnip3FL isoform ratio by inhibiting pyruvate dehydrogenase kinase
isoform 2 (PDK2) in Panc-1 cells rapidly induced mitochondrial perturbations and
cell death. The findings of the present study reveal a novel survival pathway
that functionally couples the unique glycolytic phenotype in cancer cells to
hypoxia resistance via a PDK2-dependent mechanism that switches Bnip3 from cell
death to survival. Discovery of the survival Bnip3Deltaex3 isoform may
fundamentally explain how certain cells resist Bnip3 and avert death during
hypoxia.
PMID- 26416964
TI - RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome
tethering in response to Interleukin-4.
AB - Autophagy is a key degradative pathway coordinated by external cues, including
starvation, oxidative stress, or pathogen detection. Rare are the molecules known
to contribute mechanistically to the regulation of autophagy and expressed
specifically in particular environmental contexts or in distinct cell types.
Here, we unravel the role of RUN and FYVE domain-containing protein 4 (RUFY4) as
a positive molecular regulator of macroautophagy in primary dendritic cells
(DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation
enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in
turn actively promote LC3 degradation, Syntaxin 17-positive autophagosome
formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen
presentation by MHC II and allows host control of Brucella abortus replication in
IL-4-treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first
molecule characterized to date that promotes autophagy and influences endosome
dynamics in a subset of immune cells.
PMID- 26416965
TI - mTOR and differential activation of mitochondria orchestrate neutrophil
chemotaxis.
AB - Neutrophils use chemotaxis to locate invading bacteria. Adenosine triphosphate
(ATP) release and autocrine purinergic signaling via P2Y2 receptors at the front
and A2a receptors at the back of cells regulate chemotaxis. Here, we examined the
intracellular mechanisms that control these opposing signaling mechanisms. We
found that mitochondria deliver ATP that stimulates P2Y2 receptors in response to
chemotactic cues, and that P2Y2 receptors promote mTOR signaling, which augments
mitochondrial activity near the front of cells. Blocking mTOR signaling with
rapamycin or PP242 or mitochondrial ATP production (e.g., with CCCP) reduced
mitochondrial Ca(2+) uptake and membrane potential, and impaired cellular ATP
release and neutrophil chemotaxis. Autocrine stimulation of A2a receptors causes
cyclic adenosine monophosphate accumulation at the back of cells, which inhibits
mTOR signaling and mitochondrial activity, resulting in uropod retraction. We
conclude that mitochondrial, purinergic, and mTOR signaling regulates neutrophil
chemotaxis and may be a pharmacological target in inflammatory diseases.
PMID- 26416966
TI - PC7 and the related proteases Furin and Pace4 regulate E-cadherin function during
blastocyst formation.
AB - The first cell differentiation in mammalian embryos segregates polarized
trophectoderm cells from an apolar inner cell mass (ICM). This lineage decision
is specified in compacted morulae by cell polarization and adhesion acting on the
Yes-associated protein in the Hippo signaling pathway, but the regulatory
mechanisms are unclear. We show that morula compaction and ICM formation depend
on PC7 and the related proprotein convertases (PCs) Furin and Pace4 and that
these proteases jointly regulate cell-cell adhesion mediated by E-cadherin
processing. We also mapped the spatiotemporal activity profiles of these
proteases by live imaging of a transgenic reporter substrate in wild-type and PC
mutant embryos. Differential inhibition by a common inhibitor revealed that all
three PCs are active in inner and outer cells, but in partially nonoverlapping
compartments. E-cadherin processing by multiple PCs emerges as a novel mechanism
to modulate cell-cell adhesion and fate allocation.
PMID- 26416967
TI - CRISP1 as a novel CatSper regulator that modulates sperm motility and orientation
during fertilization.
AB - Ca(2+)-dependent mechanisms are critical for successful completion of
fertilization. Here, we demonstrate that CRISP1, a sperm protein involved in
mammalian fertilization, is also present in the female gamete and capable of
modulating key sperm Ca(2+) channels. Specifically, we show that CRISP1 is
expressed by the cumulus cells that surround the egg and that fertilization of
cumulus-oocyte complexes from CRISP1 knockout females is impaired because of a
failure of sperm to penetrate the cumulus. We provide evidence that CRISP1
stimulates sperm orientation by modulating sperm hyperactivation, a vigorous
motility required for penetration of the egg vestments. Moreover, patch clamping
of sperm revealed that CRISP1 has the ability to regulate CatSper, the principal
sperm Ca(2+) channel involved in hyperactivation and essential for fertility.
Given the critical role of Ca(2+) for sperm motility, we propose a novel CRISP1
mediated fine-tuning mechanism to regulate sperm hyperactivation and orientation
for successful penetration of the cumulus during fertilization.
PMID- 26416968
TI - A Src inhibitor regulates the cell cycle of human pluripotent stem cells and
improves directed differentiation.
AB - Driving human pluripotent stem cells (hPSCs) into specific lineages is an
inefficient and challenging process. We show that a potent Src inhibitor, PP1,
regulates expression of genes involved in the G1 to S phase transition of the
cell cycle, activates proteins in the retinoblastoma family, and subsequently
increases the differentiation propensities of hPSCs into all three germ layers.
We further demonstrate that genetic suppression of Src regulates the activity of
the retinoblastoma protein and enhances the differentiation potential of hPSCs
across all germ layers. These positive effects extend beyond the initial germ
layer specification and enable efficient differentiation at subsequent stages of
differentiation.
PMID- 26416969
TI - Human substantia nigra neurons encode decision outcome and are modulated by
categorization uncertainty in an auditory categorization task.
AB - The ability to categorize stimuli - predator or prey, friend or foe - is an
essential feature of the decision-making process. Underlying that ability is the
development of an internally generated category boundary to generate decision
outcomes. While classic temporal difference reinforcement models assume midbrain
dopaminergic neurons underlie the prediction error required to learn boundary
location, these neurons also demonstrate a robust response to nonreward incentive
stimuli. More recent models suggest that this may reflect a motivational aspect
to performing a task which should be accounted for when modeling dopaminergic
neuronal behavior. To clarify the role of substantia nigra dopamine neurons in
uncertain perceptual decision making, we investigated their behavior using single
neuron extracellular recordings in patients with Parkinson's disease undergoing
deep brain stimulation. Subjects underwent a simple auditory categorical decision
making task in which they had to classify a tone as either low- or high-pitched
relative to an explicit threshold tone and received feedback but no reward. We
demonstrate that the activity of human SN dopaminergic neurons is predictive of
perceptual categorical decision outcome and is modulated by uncertainty. Neuronal
activity was highest during difficult (uncertain) decisions that resulted in
correct responses and lowest during easy decisions that resulted in incorrect
responses. This pattern of results is more consistent with a "motivational" role
with regards to perceptual categorization and suggests that dopamine neurons are
most active when critical information - as represented by uncertainty - is
available for learning decision boundaries.
PMID- 26416970
TI - Kir6.2 activation by sulfonylurea receptors: a different mechanism of action for
SUR1 and SUR2A subunits via the same residues.
AB - ATP-sensitive potassium channels (K-ATP channels) play a key role in adjusting
the membrane potential to the metabolic state of cells. They result from the
unique combination of two proteins: the sulfonylurea receptor (SUR), an ATP
binding cassette (ABC) protein, and the inward rectifier K(+) channel Kir6.2.
Both subunits associate to form a heterooctamer (4 SUR/4 Kir6.2). SUR modulates
channel gating in response to the binding of nucleotides or drugs and Kir6.2
conducts potassium ions. The activity of K-ATP channels varies with their
localization. In pancreatic beta-cells, SUR1/Kir6.2 channels are partly active at
rest while in cardiomyocytes SUR2A/Kir6.2 channels are mostly closed. This
divergence of function could be related to differences in the interaction of SUR1
and SUR2A with Kir6.2. Three residues (E1305, I1310, L1313) located in the linker
region between transmembrane domain 2 and nucleotide-binding domain 2 of SUR2A
were previously found to be involved in the activation pathway linking binding of
openers onto SUR2A and channel opening. To determine the role of the equivalent
residues in the SUR1 isoform, we designed chimeras between SUR1 and the ABC
transporter multidrug resistance-associated protein 1 (MRP1), and used patch
clamp recordings on Xenopus oocytes to assess the functionality of SUR1/MRP1
chimeric K-ATP channels. Our results reveal that the same residues in SUR1 and
SUR2A are involved in the functional association with Kir6.2, but they display
unexpected side-chain specificities which could account for the contrasted
properties of pancreatic and cardiac K-ATP channels.
PMID- 26416971
TI - Deletion of glycerol channel aquaporin-9 (Aqp9) impairs long-term blood glucose
control in C57BL/6 leptin receptor-deficient (db/db) obese mice.
AB - Deletion of the glycerol channel aquaporin-9 (Aqp9) reduces postprandial blood
glucose levels in leptin receptor-deficient (db/db) obese mice on a C57BL/6 *
C57BLKS mixed genetic background. Furthermore, shRNA-mediated reduction of Aqp9
expression reduces liver triacylglycerol (TAG) accumulation in a diet-induced rat
model of obesity. The aim of this study was to investigate metabolic effects of
Aqp9 deletion in coisogenic db/db mice of the C57BL/6 background. Aqp9(wt) db/db
and Aqp9(-/-) db/db mice did not differ in body weight and liver TAG contents. On
the C57BL/6 genetic background, we observed elevated plasma glucose in Aqp9(-/-)
db/db mice (+1.1 mmol/L, life-time average), while plasma insulin concentration
was reduced at the time of death. Glucose levels changed similarly in
pentobarbital anesthetized, glucagon challenged Aqp9(wt) db/db and Aqp9(-/-)
db/db mice. Liver transcriptional profiling did not detect differential gene
expression between genotypes. Metabolite profiling revealed a sex independent
increase in plasma glycerol (+55%) and glucose (+24%), and reduction in threonate
(all at q < 0.1) in Aqp9(-/-) db/db mice compared to controls. Metabolite
profiling thus confirms a role of AQP9 in glycerol metabolism of obese C57BL/6
db/db mice. In this animal model of obesity Aqp9 gene deletion elevates plasma
glucose and does not alleviate hepatosteatosis.
PMID- 26416972
TI - Hierarchical organization of long-range circuits in the olfactory cortices.
AB - How sensory information is processed within olfactory cortices is unclear. Here,
we examined long-range circuit wiring between different olfactory cortical
regions of acute mouse brain slices using a channelrhodopsin-2 (ChR2)-based
neuronal targeting approach. Our results provide detailed information regarding
the synaptic properties of the reciprocal long-range monosynaptic glutamatergic
projections (LRMGP) between and within anterior piriform cortex (aPC), posterior
piriform cortex (pPC), and lateral entorhinal cortex (LEC), thereby creating a
long-range inter- and intracortical circuit diagrams at the level of synapses and
single cortical neurons. Our results reveal the following information regarding
hierarchical intra- and intercortical organizations: (i) there is massive bottom
up (i.e., rostral-caudal) excitation within the LRMGP accompanied with strong
feedforward (FF) inhibition; (ii) there are convergent FF connections onto LEC
from both aPC and pPC; (iii) feedback (FB) intercortical connections are weak
with a significant fraction of presumptive silent synapses; and (iv) intra and
intercortical long-range connections lack layer specificity and their innervation
of interneurons are stronger than neighboring pyramidal neurons. The elucidation
of the distinct hierarchical organization of long-range olfactory cortical
circuits paves the way for further understanding of higher order cortical
processing within the olfactory system.
PMID- 26416973
TI - Effects of decreased lactate accumulation after dichloroacetate administration on
exercise training-induced mitochondrial adaptations in mouse skeletal muscle.
AB - Recent studies suggested that lactate accumulation can be a signal for
mitochondrial biogenesis in skeletal muscle. We investigated whether reductions
in lactate concentrations in response to dichloroacetate (DCA), an activator of
pyruvate dehydrogenase, attenuate mitochondrial adaptations after exercise
training in mice. We first confirmed that DCA administration (200 mg/kg BW by
i.p. injection) 10 min before exercise decreased muscle and blood lactate
concentrations after high-intensity interval exercise (10 bouts of 1 min
treadmill running at 40 m/min with a 1 min rest). At the same time, exercise
induced signal cascades did not change by pre-exercise DCA administration. These
results suggested that DCA administration affected only lactate concentrations
after exercise. We next examined the effects of acute DCA administration on mRNA
expressions involved with mitochondrial biogenesis after same high-intensity
interval exercise and the effects of chronic DCA administration on mitochondrial
adaptations after high-intensity interval training (increasing intensity from 38
to 43 m/min by the end of training period). Acute DCA administration did not
change most of the exercise-induced mRNA upregulation. These data suggest that
lactate reductions by DCA administration did not affect transcriptional
activation after high-intensity interval exercise. However, chronic DCA
administration attenuated, in part, mitochondrial adaptations such as training
induced increasing rates of citrate synthase (P = 0.06), beta-hydroxyacyl CoA
dehydrogenase activity (P < 0.05), cytochrome c oxidase IV (P < 0.05) and a fatty
acid transporter, fatty acid translocase/CD36 (P < 0.05), proteins after exercise
training. These results suggest that lactate accumulation during high-intensity
interval exercise may be associated with mitochondrial adaptations after chronic
exercise training.
PMID- 26416974
TI - Uteroplacental insufficiency leads to hypertension, but not glucose intolerance
or impaired skeletal muscle mitochondrial biogenesis, in 12-month-old rats.
AB - Growth restriction impacts on offspring development and increases their risk of
disease in adulthood which is exacerbated with "second hits." The aim of this
study was to investigate if blood pressure, glucose tolerance, and skeletal
muscle mitochondrial biogenesis were altered in 12-month-old male and female
offspring with prenatal or postnatal growth restriction. Bilateral uterine vessel
ligation induced uteroplacental insufficiency and growth restriction in offspring
(Restricted). A sham surgery was also performed during pregnancy (Control) and
some litters from sham mothers had their litter size reduced (Reduced litter),
which restricted postnatal growth. Growth-restricted females only developed
hypertension at 12 months, which was not observed in males. In Restricted females
only homeostasis model assessment for insulin resistance was decreased,
indicating enhanced hepatic insulin sensitivity, which was not observed in males.
Plasma leptin was increased only in the Reduced males at 12 months compared to
Control and Restricted males, which was not observed in females. Compared to
Controls, leptin, ghrelin, and adiponectin were unaltered in the Restricted males
and females, suggesting that at 12 months of age the reduction in body weight in
the Restricted offspring is not a consequence of circulating adipokines. Skeletal
muscle PGC-1alpha levels were unaltered in 12-month-old male and female rats,
which indicate improvements in lean muscle mass by 12 months of age. In summary,
sex strongly impacts the cardiometabolic effects of growth restriction in 12
month-old rats and it is females who are at particular risk of developing long
term hypertension following growth restriction.
PMID- 26416975
TI - TLR4 mutant mice are protected from renal fibrosis and chronic kidney disease
progression.
AB - Chronic kidney disease (CKD) is associated with persistent low-grade inflammation
and immunosuppression. In this study we tested the role of Toll-like receptor 4,
the main receptor for endotoxin (LPS), in a mouse model of renal fibrosis and in
a model of progressive CKD that better resembles the human disease. C3HeJ (TLR4
mutant) mice have a missense point mutation in the TLR4 gene, rendering the
receptor nonfunctional. In a model of renal fibrosis after folic acid injection,
TLR4 mutant mice developed less interstititial fibrosis in comparison to wild
type (WT) mice. Furthermore, 4 weeks after 5/6 nephrectomy with continuous low
dose angiotensin II infusion, C3HeOuJ (TLR4 WT) mice developed progressive CKD
with albuminuria, increased serum levels of BUN and creatinine,
glomerulosclerosis, and interstitial fibrosis, whereas TLR4 mutant mice were
significantly protected from CKD progression. TLR4 WT mice also developed low
grade systemic inflammation, splenocyte apoptosis and increased expression of the
immune inhibitory receptor PD-1 in the spleen, which were not observed in TLR4
mutant mice. In vitro, endotoxin (LPS) directly upregulated NLRP3 inflammasome
expression in renal epithelial cells via TLR4. In summary, TLR4 contributes to
renal fibrosis and CKD progression, at least in part, via inflammasome activation
in renal epithelial cells, and may also participate in the dysregulated immune
response that is associated with CKD.
PMID- 26416976
TI - Case report: proximal tubule impairment following volatile anesthetic exposure.
AB - The safety of contemporary volatile anesthetic agents with respect to kidney
function is well established, and growing evidence suggests that volatile
anesthetics even protect against ischemic nephropathy. However, studies examining
effects of volatile anesthetics on kidney function frequently demonstrate
transient proteinuria and glycosuria following exposure to these agents, although
the cause of these findings has not been thoroughly examined. We describe the
case of a patient who underwent a neurosurgical procedure, then experienced
glycosuria without hyperglycemia that resolved within days. Following a second
neurosurgical procedure, the patient again developed glycosuria, now associated
with ketonuria. Further examination demonstrated nonalbuminuric proteinuria in
conjunction with urinary wasting of phosphate and potassium, indicative of
proximal tubule impairment. We suggest that transient proximal tubule impairment
may play a role in the proteinuria and glycosuria described following volatile
anesthetic exposure and discuss the relationship between these observations and
the ability of these agents to protect against ischemic nephropathy.
PMID- 26416978
TI - Transcriptomic Evidence for the Evolution of Shoot Meristem Function in
Sporophyte-Dominant Land Plants through Concerted Selection of Ancestral
Gametophytic and Sporophytic Genetic Programs.
PMID- 26416977
TI - Weak endogenous Ca2+ buffering supports sustained synaptic transmission by
distinct mechanisms in rod and cone photoreceptors in salamander retina.
AB - Differences in synaptic transmission between rod and cone photoreceptors
contribute to different response kinetics in rod- versus cone-dominated visual
pathways. We examined Ca(2+) dynamics in synaptic terminals of tiger salamander
photoreceptors under conditions that mimicked endogenous buffering to determine
the influence on kinetically and mechanistically distinct components of synaptic
transmission. Measurements of IC l(Ca) confirmed that endogenous Ca(2+) buffering
is equivalent to ~0.05 mmol/L EGTA in rod and cone terminals. Confocal imaging
showed that with such buffering, depolarization stimulated large, spatially
unconstrained [Ca(2+)] increases that spread throughout photoreceptor terminals.
We calculated immediately releasable pool (IRP) size and release efficiency in
rods by deconvolving excitatory postsynaptic currents and presynaptic Ca(2+)
currents. Peak efficiency of ~0.2 vesicles/channel was similar to that of cones
(~0.3 vesicles/channel). Efficiency in both cell types was not significantly
affected by using weak endogenous Ca(2+) buffering. However, weak Ca(2+)
buffering speeded Ca(2+)/calmodulin (CaM)-dependent replenishment of vesicles to
ribbons in both rods and cones, thereby enhancing sustained release. In rods,
weak Ca(2+) buffering also amplified sustained release by enhancing CICR and CICR
stimulated release of vesicles at nonribbon sites. By contrast, elevating
[Ca(2+)] at nonribbon sites in cones with weak Ca(2+) buffering and by inhibiting
Ca(2+) extrusion did not trigger additional release, consistent with the notion
that exocytosis from cones occurs exclusively at ribbons. The presence of weak
endogenous Ca(2+) buffering in rods and cones facilitates slow, sustained
exocytosis by enhancing Ca(2+)/CaM-dependent replenishment of ribbons in both
rods and cones and by stimulating nonribbon release triggered by CICR in rods.
PMID- 26416979
TI - Anarchy Is a Molecular Signature of Worker Sterility in the Honey Bee.
AB - Worker sterility is a defining characteristic of eusociality. The existence of
the sterile worker caste remains a fundamental question for evolutionary biology
as it requires the existence of genes that reduce personal reproduction.
Currently, little is known about the proximate mechanisms underpinning worker
sterility. Studies into a mutant "anarchistic" strain (in which workers can
activate their ovaries) of honey bee, Apis mellifera, identified a list of
candidate genes that regulate ovary activation. We quantified the expression of
the four most promising candidate genes (Anarchy, Pdk1, S6k, and Ulk3) in
nonactivated and activated ovaries of wild-type workers. Ovarian expression of
Anarchy, a peroxisomal membrane protein, predicts the ovary state of workers with
88.2% accuracy. Increased expression of Anarchy in the ovary is strongly
associated with suppression of oogenesis and its expression is sensitive to the
presence of the queen. Therefore, Anarchy satisfies key criteria for a "gene
underlying altruism". When we knocked down expression of Anarchy in the ovary
using RNA interference (RNAi) we altered the expression of Buffy, a gene that
regulates programmed cell death. Whole-mount multiplex fluorescent in situ
hybridization (mFISH) shows Anarchy transcripts localize to degenerating oocytes
within the ovary. Our results suggest that Anarchy is involved in the regulation
of oogenesis through programmed cell death. The evolution of facultative worker
sterility most likely occurred when the conserved mechanism of programmed cell
death was co-opted to regulate ovary activation. Anarchy may therefore be the
first example of a gene that has evolved through kin selection to regulate worker
sterility.
PMID- 26416981
TI - Substitution Model Adequacy and Assessing the Reliability of Estimates of Virus
Evolutionary Rates and Time Scales.
AB - Determining the time scale of virus evolution is central to understanding their
origins and emergence. The phylogenetic methods commonly used for this purpose
can be misleading if the substitution model makes incorrect assumptions about the
data. Empirical studies consider a pool of models and select that with the
highest statistical fit. However, this does not allow the rejection of all
models, even if they poorly describe the data. An alternative is to use model
adequacy methods that evaluate the ability of a model to predict hypothetical
future observations. This can be done by comparing the empirical data with data
generated under the model in question. We conducted simulations to evaluate the
sensitivity of such methods with nucleotide, amino acid, and codon data. These
effectively detected underparameterized models, but failed to detect mutational
saturation and some instances of nonstationary base composition, which can lead
to biases in estimates of tree topology and length. To test the applicability of
these methods with real data, we analyzed nucleotide and amino acid data sets
from the genus Flavivirus of RNA viruses. In most cases these models were
inadequate, with the exception of a data set of relatively closely related
sequences of Dengue virus, for which the GTR+Gamma nucleotide and LG+Gamma amino
acid substitution models were adequate. Our results partly explain the lack of
consensus over estimates of the long-term evolutionary time scale of these
viruses, and indicate that assessing the adequacy of substitution models should
be routinely used to determine whether estimates are reliable.
PMID- 26416980
TI - The Roles of Compensatory Evolution and Constraint in Aminoacyl tRNA Synthetase
Evolution.
AB - Mitochondrial protein translation requires interactions between transfer RNAs
encoded by the mitochondrial genome (mt-tRNAs) and mitochondrial aminoacyl tRNA
synthetase proteins (mt-aaRS) encoded by the nuclear genome. It has been argued
that animal mt-tRNAs have higher deleterious substitution rates relative to their
nuclear-encoded counterparts, the cytoplasmic tRNAs (cyt-tRNAs). This dynamic
predicts elevated rates of compensatory evolution of mt-aaRS that interact with
mt-tRNAs, relative to aaRS that interact with cyt-tRNAs (cyt-aaRS). We find that
mt-aaRS do evolve at significantly higher rates (exemplified by higher dN and
dN/dS) relative to cyt-aaRS, across mammals, birds, and Drosophila. While this
pattern supports a model of compensatory evolution, the level at which a gene is
expressed is a more general predictor of protein evolutionary rate. We find that
gene expression level explains 10-56% of the variance in aaRS dN/dS, and that cyt
aaRS are more highly expressed in addition to having lower dN/dS values relative
to mt-aaRS, consistent with more highly expressed genes being more evolutionarily
constrained. Furthermore, we find no evidence of positive selection acting on
either class of aaRS protein, as would be expected under a model of compensatory
evolution. Nevertheless, the signature of faster mt-aaRS evolution persists in
mammalian, but not bird or Drosophila, lineages after controlling for gene
expression, suggesting some additional effect of compensatory evolution for
mammalian mt-aaRS. We conclude that gene expression is the strongest factor
governing differential amino acid substitution rates in proteins interacting with
mitochondrial versus cytoplasmic factors, with important differences in mt-aaRS
molecular evolution among taxonomic groups.
PMID- 26416982
TI - Corrigendum.
PMID- 26416983
TI - Cyclin E1 plays a key role in balancing between totipotency and differentiation
in human embryonic cells.
AB - STUDY HYPOTHESIS: We aimed to investigate if Cyclin E1 (CCNE1) plays a role in
human embryogenesis, in particular during the early developmental stages
characterized by a short cell cycle. STUDY FINDING: CCNE1 is expressed in
plenipotent human embryonic cells and plays a critical role during hESC
derivation via the naive state and, potentially, normal embryo development. WHAT
IS KNOWN ALREADY: A short cell cycle due to a truncated G1 phase has been
associated with the high developmental capacity of embryonic cells. CCNE1 is a
critical G1/S transition regulator. CCNE1 overexpression can cause shortening of
the cell cycle and it is constitutively expressed in mouse embryonic stem cells
and cancer cells. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: We investigated
expression of CCNE1 in human preimplantation embryo development and embryonic
stem cells (hESC). Functional studies included CCNE1 overexpression in hESC and
CCNE1 downregulation in the outgrowths formed by plated human blastocysts.
Analysis was performed by immunocytochemistry and quantitative real-time PCR.
Mann-Whitney statistical test was applied. MAIN RESULTS AND THE ROLE OF CHANCE:
The CCNE1 protein was ubiquitously and constitutively expressed in the
plenipotent cells of the embryo from the 4-cell stage up to and including the
full blastocyst. During blastocyst expansion, CCNE1 was downregulated in the
trophectoderm (TE) cells. CCNE1 shortly co-localized with NANOG in the inner cell
mass (ICM) of expanding blastocysts, mimicking the situation in naive hESC. In
the ICM of expanded blastocysts, which corresponds with primed hESC, CCNE1
defined a subpopulation of cells different from NANOG/POU5F1-expressing
pluripotent epiblast (EPI) cells and GATA4/SOX17-expressing primitive endoderm
(PrE) cells. This CCNE1-positive cell population was associated with visceral
endoderm based on transthyretin expression and marked the third cell lineage
within the ICM, besides EPI and PrE, which had never been described before. We
also investigated the role of CCNE1 by plating expanded blastocysts for hESC
derivation. As a result, all the cells including TE cells re-gained CCNE1 and,
consequently, NANOG expression, resembling the phenotype of naive hESC. The
inhibition of CCNE1 expression with siRNA blocked proliferation and caused
degeneration of those plated cells. LIMITATIONS, REASONS FOR CAUTION: The study
is based on a limited number of good-quality human embryos donated to research.
WIDER IMPLICATIONS OF THE FINDINGS: Our study sheds light on the processes
underlying the high developmental potential of early human embryonic cells. The
CCNE1-positive plenipotent cell type corresponds with a phenotype that enables
early human embryos to recover after fragmentation, cryodamage or (single cell)
biopsy on day 3 for preimplantation genetic diagnosis. Knowledge on the
expression and function of genes responsible for this flexibility will help us to
better understand the undifferentiated state in stem cell biology and might
enable us to improve technologies in assisted reproduction. LARGE SCALE DATA: NA
STUDY FUNDING AND COMPETING INTERESTS: This research is supported by grants from
the Fund for Scientific Research - Flanders (FWO-Vlaanderen), the Methusalem
(METH) of the VUB and Scientific Research Fond Willy Gepts of UZ Brussel. There
are no competing interests.
PMID- 26416984
TI - A 19-Year-Old Girl With Rectal Bleeding: Broadening Pediatricians' Differential
Diagnoses.
PMID- 26416986
TI - Tuberculosis elimination in Canada: Truce or victory?
PMID- 26416987
TI - Terra firma-forme dermatosis.
PMID- 26416988
TI - Child sexual abuse in Nunavut linked to suicide.
PMID- 26416990
TI - Hygiene and sanitation: medical, social and psychological concerns.
PMID- 26416989
TI - Diagnosis and management of iliofemoral deep vein thrombosis: clinical practice
guideline.
PMID- 26416991
TI - Is the US ready for ICD-10?
PMID- 26416992
TI - A 38-year-old man who uses crack cocaine.
PMID- 26416994
TI - Mental health needs targeted federal funds.
PMID- 26416993
TI - Domestic impact of tuberculosis screening among new immigrants to Ontario,
Canada.
AB - BACKGROUND: All Canadian immigrants undergo screening for tuberculosis (TB)
before immigration, and selected immigrants must undergo postimmigration
surveillance for the disease. We sought to quantify the domestic health impact of
screening for TB in all new immigrants and to identify mechanisms to enhance
effectiveness and efficiency of this screening. METHODS: We linked preimmigration
medical examination records from 944,375 immigrants who settled in Ontario
between 2002 and 2011 to active TB reporting data in Ontario between 2002 and
2011. Using a retrospective cohort study design, we measured birth country
specific rates of active TB detected through preimmigration screening and
postimmigration surveillance. We then quantified the proportion of active TB
cases among residents of Ontario born abroad that were detected through
postimmigration surveillance. Using Cox regression, we identified independent
predictors of active TB postimmigration. RESULTS: Immigrants from 6 countries
accounted for 87.3% of active TB cases detected through preimmigration screening,
and 10 countries accounted for 80.4% of cases detected through postimmigration
surveillance. Immigrants from countries with a TB (all-sites) incidence rate of
less than 30 cases per 100 000 persons resulted in pre- and postimmigration
detection of 2.4 and 0.9 cases per 100 000 immigrants, respectively.
Postimmigration surveillance detected 2.6% of active TB cases in Ontario
residents born abroad, and TB was detected a median of 18 days earlier in those
undergoing surveillance than in those who were not referred to surveillance or
who did not comply. Predictors of active TB postimmigration included radiographic
markers of old TB, birth country, immigration category, location of application
for residency, immune status and age. INTERPRETATION: Universal screening for TB
in new immigrants has a modest impact on the domestic burden of active TB and is
highly inefficient. Focusing preimmigration screening in countries with high
incidence rates and revising criteria for postimmigration surveillance could
increase the effectiveness and efficiency of screening.
PMID- 26416995
TI - Social participation and coronary heart disease risk in a large prospective study
of UK women.
AB - BACKGROUND: Participation in social activities is thought to prevent heart
disease, but evidence is inconclusive. DESIGN: We assessed whether participating
in social activities reduces the risk of coronary heart disease (CHD) in a large
prospective study of 735,159 middle-aged UK women. METHODS: Women reported their
participation in eight social activities (religious group, voluntary work, adult
education, art/craft/music, dancing, sports club, yoga, bingo) and were followed
for first CHD event (hospital admission or death) over the next 8.6 years. Cox
regression models were used to estimate relative risks for CHD incidence by
participation in each and in any of the social activities. RESULTS: After
adjustment for age and region only, every activity except bingo was associated
with a reduced risk of CHD (n = 30,756 cases in total). However, after additional
adjustment for 11 factors (deprivation, education, smoking, physical activity,
body mass index, alcohol, marital status, self-rated health, happiness,
hypertension, diabetes), every relative risk estimate moved close to 1.0. For
example, for participation in any of the activities compared with none, the
relative risk adjusted for age and region only was 0.83 (99% confidence interval
0.81-0.86), but changed to 1.06 (99% confidence interval 1.02-1.09) after
additional adjustment. Adjustment for education, self-rated health, smoking and
physical activity attenuated the associations most strongly. Residual confounding
and other unmeasured factors may well account for any small remaining
associations. CONCLUSIONS: Associations between participation in various social
activities and CHD risk appear to be largely or wholly due to confounding by
personal characteristics of the participants.
PMID- 26416996
TI - Impacts of intensive follow-up on the long-term prognosis of percutaneous
coronary intervention in acute coronary syndrome patients - a single center
prospective randomized controlled study in a Chinese population.
AB - OBJECTIVES: To investigate the impact of cardiologist-coordinated intensive
follow-up on the long-term prognosis of percutaneous coronary intervention in
Chinese patients. METHODS: We recruited 964 patients who had acute coronary
syndrome and underwent successful percutaneous coronary intervention in the First
Hospital Affiliated to Henan University of Science and Technology, China.
Participants were randomly assigned into the intensive follow-up (n = 479) and
usual follow-up group (control group, n = 485). They received secondary
prevention education during hospitalization and telephone follow-ups after
discharge. The control group received telephone calls from nurses, while the
intensive follow-up group received telephone calls and medical consultations from
cardiologists. Both groups were followed up for 36 months. RESULTS: (1) At 36
months, the proportions of all-cause death, cardiac death and cumulative major
adverse cardiovascular events (MACEs) were 5.3%, 4.4% and 18.6% in the intensive
follow-up group. These events were significantly lower than in the control group
(10.1%, 9.3 % and 28.8% (p = 0.004, p = 0.003 and p < 0.001). (2) Multivariable
Cox regression analysis identified intensive follow-up as an independent
predictor of survival, cardiac death-free survival and MACE-free survival.
(hazard ratio (HR) = 0.487, 95% confidence interval (CI) 0.298-0.797, p = 0.004;
HR = 0.466, 95% CI 0.274-0.793, p = 0.005; HR = 0.614, 95% CI 0.464-0.811, p =
0.001). Kaplan-Meier analysis revealed that patients in the intensive follow-up
groups had longer survival (log rank = 8.565, p = 0.003), cardiac death-free
survival (log rank = 8.769, p = 0.003) and MACE-free survival (log rank = 15.928,
p < 0.001). (3) The average medical cost was significantly less in the intensive
follow-up group, especially the cost for re-hospitalization (US$582.74 +/-
1753.20 vs. US$999.32 +/- 2434.57, p = 0.003). The bleeding events were similar.
(4) Patients in the intensive follow-up group had significantly better controls
of cardiovascular risk factors and medication adherence. CONCLUSIONS: A
cardiologist-coordinated intensive follow-up program markedly decreased
cardiovascular risk factors, reduced medical costs, promoted medication adherence
and improved the long-term prognosis of patients after percutaneous coronary
intervention in the Chinese population.
PMID- 26416998
TI - Oncologists' Experiences and Attitudes About Their Role in Philanthropy and
Soliciting Donations From Grateful Patients.
AB - PURPOSE: Physician participation in philanthropy is important to marshal
resources that allow hospitals to pursue their missions, but little is known
about how physicians participate and their attitudes toward participation.
METHODS: To characterize philanthropic roles physicians play and their attitudes
about participation and its ethical acceptability, medical oncologists affiliated
with the 40 National Cancer Institute-designated comprehensive cancer centers
were randomly sampled and surveyed to evaluate experiences and attitudes
regarding participation in philanthropy at their institutions. Responses were
tabulated; significant associations by physicians' characteristics were explored.
RESULTS: A total of 405 (52%) physicians responded; 62% were men, and 72% were
white. Most (71%) had been exposed to their institution's fundraising/development
staff; 48% of those were taught how to identify patients who would be good
donors; 26% received information about ethical guidelines for soliciting
donations from their patients; 21% were taught how their institution ensures
Health Insurance Portability and Accountability Act compliance. A third (32%) of
respondents had been asked to directly solicit a donation from their patients for
their institution, of whom half declined to do so. Those who had solicited from
their patients had been in practice significantly longer (mean, 19 v 13 years; P
< .001). A substantial minority (37%) felt comfortable talking to their patients
about donation (men more than women, 43% v 26%; P = .008); however, 74% agreed it
could interfere with the physician-patient relationship, and 52% believe conflict
of interest exists. CONCLUSION: Institutions are asking physicians to directly
solicit their patients for donations with variability in physicians' perceptions
of the impact on relationships with patients and responses toward those requests.
PMID- 26416997
TI - Intratumoral Heterogeneity of ALK-Rearranged and ALK/EGFR Coaltered Lung
Adenocarcinoma.
AB - PURPOSE: Genetic intratumoral heterogeneity has a profound influence on the
selection of clinical treatment strategies and on addressing resistance to
targeted therapy. The purpose of this study was to explore the potential effect
of intratumoral heterogeneity on both genetic and pathologic characteristics of
ALK-rearranged lung adenocarcinoma (LADC). METHODS: We tested ALK fusions and
EGFR mutations in 629 patients with LADC by using laser-capture microdissection
to capture spatially separated tumor cell subpopulations in various
adenocarcinoma subtypes and to test for ALK fusions and EGFR mutations in ALK
rearranged, EGFR-mutated, and ALK/EGFR coaltered LADCs to compare the oncogenic
driver status between different tumor cell subpopulations in the same primary
tumor. RESULTS: Among the 629 patients, 30 (4.8%) had ALK fusions, 364 (57.9%)
had EGFR mutations, and two had ALK fusions that coexisted with EGFR mutations.
Intratumoral heterogeneity of ALK fusions were identified in nine patients by
reverse-transcriptase polymerase chain reaction. In the two patients with an
ALK/EGFR coaltered status, genetic intratumoral heterogeneity was observed both
between different growth patterns and within the same growth pattern. The
relative abundance of ALK and EGFR alterations was different in the same captured
area. ALK fusions were positively associated with a micropapillary pattern (P =
.002) and were negatively associated with a lepidic pattern (P = .008) in an
expanded statistical analysis of 900 individual adenocarcinoma components,
although they appeared to be more common in acinar-predominant LADCs in the
analysis of 629 patients. CONCLUSION: Intratumoral genetic heterogeneity was
demonstrated to coexist with histologic heterogeneity in both single-driver and
ALK/EGFR coaltered LADCs. Altered oncogenic drivers in spatially separated
subclones of the same tumor may be different.
PMID- 26416999
TI - Epirubicin Plus Cyclophosphamide Followed by Docetaxel Versus Epirubicin Plus
Docetaxel Followed by Capecitabine As Adjuvant Therapy for Node-Positive Early
Breast Cancer: Results From the GEICAM/2003-10 Study.
AB - PURPOSE: Capecitabine is an active drug in metastatic breast cancer (BC).
GEICAM/2003-10 is an adjuvant trial to investigate the integration of
capecitabine into a regimen of epirubicin and docetaxel for node-positive early
BC. PATIENTS AND METHODS: Patients with operable node-positive BC (T1-3/N1-3)
were eligible. After surgery, 1,384 patients were randomly assigned to receive
epirubicin plus cyclophosphamide (EC; 90 and 600 mg/m(2), respectively, * four
cycles), followed by docetaxel (100 mg/m(2) * four cycles; EC-T) or epirubicin
plus docetaxel (ET; 90 and 75 mg/m(2), respectively, * four cycles), followed by
capecitabine (1,250 mg/m(2) twice a day on days 1 to 14, * four cycles; ET-X);
all regimens were given every 3 weeks. The primary end point was invasive disease
free survival. Secondary end points included safety (with an alopecia-specific
study) and overall survival (OS). RESULTS: After a median follow-up of 6.6 years
and 297 events, 86% of patients who received EC-T and 82% of those who received
ET-X were invasive disease free at 5 years (hazard ratio, 1.30; 95% CI, 1.03 to
1.64; log-rank P = .03). The OS difference between arms was not statistically
significant (hazard ratio, 1.13; 95% CI, 0.82 to 1.55; log-rank P = .46). The
most frequent grade 3 to 4 adverse events in the EC-T versus ET-X arms were
neutropenia (19% v 10%), with 7% febrile neutropenia across arms; fatigue (13% v
11%); diarrhea (3% v 11%); hand-foot syndrome (2% v 20%); mucositis (6% v 5%);
vomiting (both, 5%); and myalgia (4.5% v 1%). Incomplete scalp hair recovery was
more frequent in the EC-T than ET-X arm (30% v 14%), and patients who received EC
T wore wigs significantly longer than those who received ET-X (8.35 v 6.03
months). CONCLUSION: Invasive disease-free survival, but not OS, was
significantly superior for patients with node-positive early BC who received the
adjuvant standard schedule EC-T than for those who received the experimental ET-X
regimen. Toxicity profiles differed substantially across arms.
PMID- 26417000
TI - Evolutionary Precision Medicine: A Role for Repeat Epidermal Growth Factor
Receptor Analysis in ALK-Rearranged Lung Adenocarcinoma?
PMID- 26417001
TI - Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer:
Results of the AHT Randomized Trial.
AB - PURPOSE: To assess the effects of adjuvant hormone therapy (AHT) on survival and
disease outcome in women with epithelial ovarian cancer. PATIENTS AND METHODS:
Participants were premenopausal and postmenopausal women who had been diagnosed
with epithelial ovarian cancer (any International Federation of Gynecology and
Obstetrics stage) 9 or fewer months previously. Ineligible patients included
those with deliberately preserved ovarian function, with a history of a hormone
dependent malignancy, or with any contraindications to hormone-replacement
therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT
for 5 years after random assignment or no AHT (control). Main outcome measures
were overall survival (OS), defined as time from random assignment to death (any
cause), and relapse-free survival, defined as time from random assignment to
relapse or death (any cause). Patients who continued, alive and relapse free,
were censored at their last known follow-up. RESULTS: A total of 150 patients (n
= 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19
centers in the United Kingdom, Spain, and Hungary; all patients were included in
intention-to-treat analyses. The median follow-up in alive patients is currently
19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68
(91%) of 75 patients in the control group. OS was significantly improved in
patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P =
.011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67;
95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known
prognostic factors. CONCLUSION: These results show that women who have severe
menopausal symptoms after ovarian cancer treatment can safely take hormone
replacement therapy, and this may, in fact, infer benefits in terms of OS in
addition to known advantages in terms of quality of life.
PMID- 26417002
TI - Psychosocial Outcomes in Adult Survivors of Retinoblastoma.
AB - PURPOSE: Survival rates for individuals diagnosed with retinoblastoma (RB) exceed
95% in the United States; however, little is known about the long-term
psychosocial outcomes of these survivors. PATIENTS AND METHODS: Adult RB
survivors, diagnosed from 1932 to 1994 and treated in New York, completed a
comprehensive questionnaire adapted from the Childhood Cancer Survivor Study
(CCSS), by mail or telephone. Psychosocial outcomes included psychological
distress, anxiety, depression, somatization, fear of cancer recurrence,
satisfaction with facial appearance, post-traumatic growth, and post-traumatic
stress symptoms; noncancer CCSS siblings served as a comparison group. RESULTS: A
total of 470 RB survivors (53.6% with bilateral RB; 52.1% female) and 2,820 CCSS
siblings were 43.3 (standard deviation [SD], 11) years and 33.2 (SD, 8.4) years
old at the time of study, respectively. After adjusting for sociodemographic
factors, RB survivors did not have significantly higher rates of depression,
somatization, distress, or anxiety compared with CCSS siblings. Although RB
survivors were more likely to report post-traumatic stress symptoms of avoidance
and/or hyperarousal (both P < .01), only five (1.1%) of 470 met criteria for post
traumatic stress disorder. Among survivors, having a chronic medical condition
did not increase the likelihood of psychological problems. Bilateral RB survivors
were more likely than unilateral RB survivors to experience fears of cancer
recurrence (P < .01) and worry about their children being diagnosed with RB (P <
.01). However, bilateral RB survivors were no more likely to report depression,
anxiety, or somatic complaints than unilateral survivors. CONCLUSION: Most RB
survivors do not have poorer psychosocial functioning compared with a noncancer
sample. In addition, bilateral and unilateral RB survivors seem similar with
respect to their psychological symptoms.
PMID- 26417003
TI - Perceived discrimination is associated with health behaviours among African
Americans in the Jackson Heart Study.
AB - BACKGROUND: Using Jackson Heart Study data, we examined associations of multiple
measures of perceived discrimination with health behaviours among African
Americans (AA). METHODS: The cross-sectional associations of everyday, lifetime
and burden of discrimination with odds of smoking and mean differences in
physical activity, dietary fat and sleep were examined among 4925 participants
aged 35-84 years after adjustment for age and socioeconomic status (SES).
RESULTS: Men reported slightly higher levels of everyday and lifetime
discrimination than women and similar levels of burden of discrimination as
women. After adjustment for age and SES, everyday discrimination was associated
with more smoking and a greater percentage of dietary fat in men and women (OR
for smoking: 1.13, 95% CI 1.00 to 1.28 and 1.19, 95% CI 1.05 to 1.34; mean
difference in dietary fat: 0.37, p<0.05 and 0.43, p<0.01, in men and women,
respectively). Everyday and lifetime discrimination were associated with fewer
hours of sleep in men and women (mean difference for everyday discrimination:
0.08, p<0.05 and -0.18, p<0.001, respectively; and mean difference for lifetime
discrimination: -0.08, p<0.05 and -0.24, p<0.001, respectively). Burden of
discrimination was associated with more smoking and fewer hours of sleep in women
only. CONCLUSIONS: Higher levels of perceived discrimination were associated with
select health behaviours among men and women. Health behaviours offer a potential
mechanism through which perceived discrimination affects health in AA.
PMID- 26417004
TI - Interleukin-27 inhibits ectopic lymphoid-like structure development in early
inflammatory arthritis.
AB - Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs
often develop at sites of chronic inflammation where they contribute to immune
mediated pathology. Through evaluation of synovial tissues from rheumatoid
arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression
corresponds with an increased incidence of ELS and gene signatures associated
with their development and activity. The presence of synovial ELS was also noted
in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory
arthritis. Here, pathology was associated with increased synovial expression of
pro-inflammatory cytokines, homeostatic chemokines, and transcriptional
regulators linked with lymphoid neogenesis. In both clinical and experimental RA,
synovial ELS coincided with the heightened local expression of cytokines and
transcription factors of the Th17 and T follicular helper (Tfh) cell lineages,
and included podoplanin-expressing T cells within lymphoid aggregates. IL-27
inhibited the differentiation of podoplanin-expressing Th17 cells, and an
increased number of these cells were observed in IL-27R-deficient mice with
inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS
development in RA through control of effector T cells. These studies open new
opportunities for patient stratification and treatment.
PMID- 26417005
TI - CCR4 promotes medullary entry and thymocyte-dendritic cell interactions required
for central tolerance.
AB - Autoimmunity results from a breakdown in central or peripheral tolerance. To
establish central tolerance, developing T cells must enter the thymic medulla,
where they scan antigen-presenting cells (APCs) displaying a diverse array of
autoantigens. If a thymocyte is activated by a self-antigen, the cell undergoes
either deletion or diversion into the regulatory T cell (T reg) lineage, thus
maintaining self-tolerance. Mechanisms promoting thymocyte medullary entry and
interactions with APCs are incompletely understood. CCR4 is poised to contribute
to central tolerance due to its expression by post-positive selection thymocytes,
and expression of its ligands by medullary thymic dendritic cells (DCs). Here, we
use two-photon time-lapse microscopy to demonstrate that CCR4 promotes medullary
entry of the earliest post-positive selection thymocytes, as well as efficient
interactions between medullary thymocytes and DCs. In keeping with the
contribution of thymic DCs to central tolerance, CCR4 is involved in regulating
negative selection of polyclonal and T cell receptor (TCR) transgenic thymocytes.
In the absence of CCR4, autoreactive T cells accumulate in secondary lymphoid
organs and autoimmunity ensues. These studies reveal a previously unappreciated
role for CCR4 in the establishment of central tolerance.
PMID- 26417007
TI - Floral Induction in Arabidopsis by FLOWERING LOCUS T Requires Direct Repression
of BLADE-ON-PETIOLE Genes by the Homeodomain Protein PENNYWISE.
AB - Flowers form on the flanks of the shoot apical meristem (SAM) in response to
environmental and endogenous cues. In Arabidopsis (Arabidopsis thaliana), the
photoperiodic pathway acts through FLOWERING LOCUS T (FT) to promote floral
induction in response to day length. A complex between FT and the basic leucine
zipper transcription factor FD is proposed to form in the SAM, leading to
activation of APETALA1 and LEAFY and thereby promoting floral meristem identity.
We identified mutations that suppress FT function and recovered a new allele of
the homeodomain transcription factor PENNYWISE (PNY). Genetic and molecular
analyses showed that ectopic expression of BLADE-ON-PETIOLE1 (BOP1) and BOP2,
which encode transcriptional coactivators, in the SAM during vegetative
development, confers the late flowering of pny mutants. In wild-type plants, BOP1
and BOP2 are expressed in lateral organs close to boundaries of the SAM, whereas
in pny mutants, their expression occurs in the SAM. This ectopic expression
lowers FD mRNA levels, reducing responsiveness to FT and impairing activation of
APETALA1 and LEAFY. We show that PNY binds to the promoters of BOP1 and BOP2,
repressing their transcription. These results demonstrate a direct role for PNY
in defining the spatial expression patterns of boundary genes and the
significance of this process for floral induction by FT.
PMID- 26417006
TI - Repression of Lateral Organ Boundary Genes by PENNYWISE and POUND-FOOLISH Is
Essential for Meristem Maintenance and Flowering in Arabidopsis.
AB - In the model plant Arabidopsis (Arabidopsis thaliana), endogenous and
environmental signals acting on the shoot apical meristem cause acquisition of
inflorescence meristem fate. This results in changed patterns of aerial
development seen as the transition from making leaves to the production of
flowers separated by elongated internodes. Two related BEL1-like homeobox genes,
PENNYWISE (PNY) and POUND-FOOLISH (PNF), fulfill this transition. Loss of
function of these genes impairs stem cell maintenance and blocks internode
elongation and flowering. We show here that pny pnf apices misexpress lateral
organ boundary genes BLADE-ON-PETIOLE1/2 (BOP1/2) and KNOTTED-LIKE FROM
ARABIDOPSIS THALIANA6 (KNAT6) together with ARABIDOPSIS THALIANA HOMEOBOX GENE1
(ATH1). Inactivation of genes in this module fully rescues pny pnf defects. We
further show that BOP1 directly activates ATH1, whereas activation of KNAT6 is
indirect. The pny pnf restoration correlates with renewed accumulation of
transcripts conferring floral meristem identity, including FD, SQUAMOSA PROMOTER
BINDING PROTEIN LIKE genes, LEAFY, and APETALA1. To gain insight into how this
module blocks flowering, we analyzed the transcriptome of BOP1-overexpressing
plants. Our data suggest a central role for the microRNA156-SQUAMOSA PROMOTER
BINDING PROTEIN-LIKE-microRNA172 module in integrating stress signals conferred
in part by promotion of jasmonic acid biosynthesis. These data reveal a potential
mechanism by which repression of lateral organ boundary genes by PNY-PNF is
essential for flowering.
PMID- 26417008
TI - 9-Lipoxygenase-Derived Oxylipins Activate Brassinosteroid Signaling to Promote
Cell Wall-Based Defense and Limit Pathogen Infection.
AB - The oxylipins, a large family of oxygenated lipid derivatives, regulate plant
development and immunity. Two members of the 9-lipoxygenase (9-LOX) oxylipin
pathway, 9-hydroxyoctadecatrienoic acid and 9-ketooctadecatrienoic acid, control
root development and plant defense. Studies in Arabidopsis (Arabidopsis thaliana)
using a series of 9-hydroxyoctadecatrienoic acid- and 9-ketooctadecatrienoic acid
insensitive nonresponding to oxylipins (noxy) mutants showed the importance of
the cell wall as a 9-LOX-induced defense component and the participation of NOXY
proteins in signaling cell wall damage. Here, we examined 9-LOX signaling using
the mutants lox1lox5, which lacks 9-LOX activity, and noxy2-2, which shows
oxylipin insensitivity and mitochondrial dysfunction. Mutants in brassinosteroids
(BRs), a class of plant hormones necessary for normal plant growth and the
control of cell wall integrity, were also analyzed. Several lines of evidence
indicated that 9-LOX-derived oxylipins induce BR synthesis and signaling to
activate cell wall-based responses such as callose deposition and that
constitutive activation of BR signaling in bri1-EMS-suppressor 1-D (bes1-D)
plants enhances this response. We found that constitutive BR signaling in bes1-D
and brassinolide-resistant 1-1D (bzr1-1D) mutants conferred resistance to
Pseudomonas syringae. bes1-D and bzr1-1D showed increased resistance to
Golovinomyces cichoracearum, an obligate biotrophic fungus that penetrates the
cell wall for successful infection, whereas susceptibility was enhanced in
lox1lox5 and noxy2-2. Our results indicate a sequential action of 9-LOX and BR
signaling in activating cell wall-based defense, and this response prevents
pathogen infection. These results show interaction between the 9-LOX and BR
pathways and help to clarify their role in modulating plant defense.
PMID- 26417010
TI - Remora fish suction pad attachment is enhanced by spinule friction.
AB - The remora fishes are capable of adhering to a wide variety of natural and
artificial marine substrates using a dorsal suction pad. The pad is made of
serial parallel pectinated lamellae, which are homologous to the dorsal fin
elements of other fishes. Small tooth-like projections of mineralized tissue from
the dorsal pad lamella, known as spinules, are thought to increase the remora's
resistance to slippage and thereby enhance friction to maintain attachment to a
moving host. In this work, the geometry of the spinules and host topology as
determined by micro-computed tomography and confocal microscope data,
respectively, are combined in a friction model to estimate the spinule
contribution to shear resistance. Model results are validated with natural and
artificially created spinules and compared with previous remora pull-off
experiments. It was found that spinule geometry plays an essential role in
friction enhancement, especially at short spatial wavelengths in the host
surface, and that spinule tip geometry is not correlated with lamellar position.
Furthermore, comparisons with pull-off experiments suggest that spinules are
primarily responsible for friction enhancement on rough host topologies such as
shark skin.
PMID- 26417009
TI - Functional Analysis of the Arabidopsis TETRASPANIN Gene Family in Plant Growth
and Development.
AB - TETRASPANIN (TET) genes encode conserved integral membrane proteins that are
known in animals to function in cellular communication during gamete fusion,
immunity reaction, and pathogen recognition. In plants, functional information is
limited to one of the 17 members of the Arabidopsis (Arabidopsis thaliana) TET
gene family and to expression data in reproductive stages. Here, the promoter
activity of all 17 Arabidopsis TET genes was investigated by pAtTET::NUCLEAR
LOCALIZATION SIGNAL-GREEN FLUORESCENT PROTEIN/beta-GLUCURONIDASE reporter lines
throughout the life cycle, which predicted functional divergence in the
paralogous genes per clade. However, partial overlap was observed for many TET
genes across the clades, correlating with few phenotypes in single mutants and,
therefore, requiring double mutant combinations for functional investigation.
Mutational analysis showed a role for TET13 in primary root growth and lateral
root development and redundant roles for TET5 and TET6 in leaf and root growth
through negative regulation of cell proliferation. Strikingly, a number of TET
genes were expressed in embryonic and seedling progenitor cells and remained
expressed until the differentiation state in the mature plant, suggesting a
dynamic function over developmental stages. The cis-regulatory elements together
with transcription factor-binding data provided molecular insight into the sites,
conditions, and perturbations that affect TET gene expression and positioned the
TET genes in different molecular pathways; the data represent a hypothesis
generating resource for further functional analyses.
PMID- 26417011
TI - Larger lacertid lizard species produce higher than expected iliotibialis muscle
power output: the evolution of muscle contractile mechanics with body size.
AB - Increases in body size can lead to alterations in morphology, physiology,
locomotor performance and behaviour of animals. Most studies considering the
effects of scaling on muscle performance have studied within-species effects,
with few studies considering differences between species. A previous review of
published data indicates that maximum muscle-shortening velocity decreases, but
that maximum isometric stress does not change, with increased body mass across
species of terrestrial animals. However, such previous analyses do not account
for the phylogenetic relatedness of the species studied. Our aim was to use
phylogenetically informed analysis to determine the effects of body size on
isolated iliotibialis muscle performance across 17 species of lacertid lizards.
Between one and five individuals were used to obtain mean performance values for
each species. We analysed the relationship between each variable and body size,
as estimated by snout-vent length (SVL), whilst taking into account the
phylogenetic relationships between species. We found that isometric tetanus
relaxation time, maximal tetanus stress (force per muscle cross-sectional area)
and maximal work loop power output (normalised to muscle mass) all significantly
increased with greater SVL. In contrast, fatigue resistance during repeated work
loops significantly decreased with SVL and there was no effect of size on tetanus
activation time. When we compare our findings with those that would be predicted
by dynamic similarity, then as these lacertid species become bigger, there is a
greater than expected increase in the normalised muscle power output, probably to
counter the larger than expected increase in body mass.
PMID- 26417012
TI - Transcriptome profiling reveals mechanisms for the evolution of insect
seasonality.
AB - Rapid evolutionary change in seasonal timing can facilitate ecological speciation
and resilience to climate warming. However, the molecular mechanisms behind
shifts in animal seasonality are still unclear. Evolved differences in
seasonality occur in the European corn borer moth (Ostrinia nubilalis), in which
early summer emergence in E-strain adults and later summer emergence in Z-strain
adults is explained by a shift in the length of the termination phase of larval
diapause. Here, we sample from the developmental time course of diapause in both
strains and use transcriptome sequencing to profile regulatory and amino acid
changes associated with timing divergence. Within a previously defined
quantitative trait locus (QTL), we nominate 48 candidate genes, including several
in the insulin signaling and circadian rhythm pathways. Genome-wide
transcriptional activity is negligible during the extended Z-strain termination,
whereas shorter E-strain termination is characterized by a rapid burst of
regulatory changes involved in resumption of the cell cycle, hormone production
and stress response. Although gene expression during diapause termination in
Ostrinia is similar to that found previously in flies, nominated genes for shifts
in timing are species specific. Hence, across distant relatives the evolution of
insect seasonality appears to involve unique genetic switches that direct
organisms into distinct phases of the diapause pathway through wholesale
restructuring of conserved gene regulatory networks.
PMID- 26417013
TI - Acquisition and expression of memories of distance and direction in navigating
wood ants.
AB - Wood ants, like other central place foragers, rely on route memories to guide
them to and from a reliable food source. They use visual memories of the
surrounding scene and probably compass information to control their direction. Do
they also remember the length of their route and do they link memories of
direction and distance? To answer these questions, we trained wood ant (Formica
rufa) foragers in a channel to perform either a single short foraging route or
two foraging routes in opposite directions. By shifting the starting position of
the route within the channel, but keeping the direction and distance fixed, we
tried to ensure that the ants would rely upon vector memories rather than visual
memories to decide when to stop. The homeward memories that the ants formed were
revealed by placing fed or unfed ants directly into a channel and assessing the
direction and distance that they walked without prior performance of the food
ward leg of the journey. This procedure prevented the distance and direction
walked being affected by a home vector derived from path integration. Ants that
were unfed walked in the feeder direction. Fed ants walked in the opposite
direction for a distance related to the separation between start and feeder.
Vector memories of a return route can thus be primed by the ants' feeding state
and expressed even when the ants have not performed the food-ward route. Tests on
ants that have acquired two routes indicate that memories of the direction and
distance of the return routes are linked, suggesting that they may be encoded by
a common neural population within the ant brain.
PMID- 26417014
TI - Patterns of oxygen consumption during simultaneously occurring elevated metabolic
states in the viviparous snake Thamnophis marcianus.
AB - Snakes exhibit large factorial increments in oxygen consumption during digestion
and physical activity, and long-lasting sub-maximal increments during
reproduction. Under natural conditions, all three physiological states may occur
simultaneously, but the integrated response is not well understood. Adult male
and female checkered gartersnakes (Thamnophis marcianus) were used to examine
increments in oxygen consumption (i.e. V(O2)) and carbon dioxide production (i.e.
V(CO2)) associated with activity (Act), digestion (Dig) and post-prandial
activity (Act+Dig). For females, we carried out these trials in the non
reproductive state, and also during the vitellogenic (V) and embryogenic (E)
phases of a reproductive cycle. Endurance time (i.e. time to exhaustion, TTE) was
recorded for all groups during Act and Act+Dig trials. Our results indicate that
male and non-reproductive female T. marcianus exhibit significant increments in
V(O2) during digestion (~5-fold) and activity (~9-fold), and that Act+Dig results
in a similar increment in V(O2) (~9- to 10-fold). During reproduction, resting
V(O2) increased by 1.6- to 1.7-fold, and peak increments during digestion were
elevated by 30-50% above non-reproductive values, but values associated with Act
and Act+Dig were not significantly different from non-reproductive values. During
Act+Dig, endurance time remained similar for all of the groups in the present
study. Overall, our results indicate that prioritization is the primary pattern
of interaction in oxygen delivery exhibited by this species. We propose that the
metabolic processes associated with digestion, and perhaps reproduction, are
temporarily compromised during activity.
PMID- 26417015
TI - Interactive effects of seawater acidification and elevated temperature on
biomineralization and amino acid metabolism in the mussel Mytilus edulis.
AB - Seawater acidification and warming resulting from anthropogenic production of
carbon dioxide are increasing threats to marine ecosystems. Previous studies have
documented the effects of either seawater acidification or warming on marine
calcifiers; however, the combined effects of these stressors are poorly
understood. In our study, we examined the interactive effects of elevated carbon
dioxide partial pressure (P(CO2)) and temperature on biomineralization and amino
acid content in an ecologically and economically important mussel, Mytilus
edulis. Adult M. edulis were reared at different combinations of P(CO2) (pH 8.1
and 7.8) and temperature (19, 22 and 25 degrees C) for 2 months. The results
indicated that elevated P(CO2) significantly decreased the net calcification
rate, the calcium content and the Ca/Mg ratio of the shells, induced the
differential expression of biomineralization-related genes, modified shell
ultrastructure and altered amino acid content, implying significant effects of
seawater acidification on biomineralization and amino acid metabolism. Notably,
elevated temperature enhanced the effects of seawater acidification on these
parameters. The shell breaking force significantly decreased under elevated
P(CO2), but the effect was not exacerbated by elevated temperature. The results
suggest that the interactive effects of seawater acidification and elevated
temperature on mussels are likely to have ecological and functional implications.
This study is therefore helpful for better understanding the underlying effects
of changing marine environments on mussels and other marine calcifiers.
PMID- 26417016
TI - Chela asymmetry in a durophagous crab: predominance of right-handedness and
handedness reversal is linked to chela size and closing force.
AB - The swimming crab Portunus trituberculatus is a durophagous brachyuran. Right
handed crabs are predominant, but left-handed crabs are also found in nature.
Left-handedness may arise from loss of the right crusher. We examined whether
heterochely (morphology) was correlated with differences in closing force
(physical property) and handedness (behaviour). The closing force was stronger in
larger chela with greater apodeme height and handedness resided in the chela with
stronger closing force. With loss of the right chela (autotomy), handedness
transitioned from the right to left chela, and all crabs were left-handed
thereafter. Reversed handedness was accompanied with a reduction of size and
closing force in the regenerated right chela, and growth of the original left
chela. After handedness reversal, dentition on the left dactylus of the newly
converted crusher was close to that of the original right crusher, but did not
attain the same shape, even after 10 moults. Left-handed crabs were significantly
worse than right-handed crabs at crushing hard-shelled prey. Chela formation was
symmetrical in the zoea, and heterochely and right-handedness started in the
megalopa, regardless of maternal handedness. Since the left chela is capable of
being the crusher, heterochely may be caused by differences in morphogenetic
velocity between the right and left chelae, under a signal discriminating right
from left. Right-handedness is an attribute of P. trituberculatus, that would be
inheritable across generations. It is probable that right-handedness was used in
the earliest durophagous crabs, and this trend has been succeeded to extant
species.
PMID- 26417017
TI - Whole genome duplications in plants: an overview from Arabidopsis.
AB - Polyploidy is a common event in plants that involves the acquisition of more than
two complete sets of chromosomes. Allopolyploidy originates from interspecies
hybrids while autopolyploidy originates from intraspecies whole genome
duplication (WGD) events. In spite of inconveniences derived from chromosomic
rearrangement during polyploidization, natural plant polyploids species often
exhibit improved growth vigour and adaptation to adverse environments, conferring
evolutionary advantages. These advantages have also been incorporated into crop
breeding programmes. Many tetraploid crops show increased stress tolerance,
although the molecular mechanisms underlying these different adaptation abilities
are poorly known. Understanding the physiological, cellular, and molecular
mechanisms coupled to WGD, in both allo- and autopolyploidy, is a major
challenge. Over the last few years, several studies, many of them in Arabidopsis,
are shedding light on the basis of genetic, genomic, and epigenomic changes
linked to WGD. In this review we summarize and discuss the latest advances made
in Arabidopsis polyploidy, but also in other agronomic plant species.
PMID- 26417018
TI - HvEXPB7, a novel beta-expansin gene revealed by the root hair transcriptome of
Tibetan wild barley, improves root hair growth under drought stress.
AB - Tibetan wild barley is a treasure trove of useful genes for crop improvement
including abiotic stress tolerance, like drought. Root hair of single-celled
structures plays an important role in water and nutrition uptake. Polyethylene
glycol-induced drought stress hydroponic/petri-dish experiments were performed,
where root hair morphology and transcriptional characteristics of two contrasting
Tibetan wild barley genotypes (drought-tolerant XZ5 and drought-sensitive XZ54)
and drought-tolerant cv. Tadmor were compared. Drought-induced root hair growth
was only observed in XZ5. Thirty-six drought tolerance-associated genes were
identified in XZ5, including 16 genes specifically highly expressed in XZ5 but
not Tadmor under drought. The full length cDNA of a novel beta-expansin gene
(HvEXPB7), being the unique root hair development related gene in the identified
genes, was cloned. The sequence comparison indicated that HvEXPB7 carried both
DPBB_1 and Pollon_allerg_1 domains. HvEXPB7 is predominantly expressed in roots.
Subcellular localization verified that HvEXPB7 is located in the plasma membrane.
Barley stripe mosaic virus induced gene silencing (BSMV-VIGS) of HvEXPB7 led to
severely suppressed root hairs both under control and drought conditions, and
significantly reduced K uptake. These findings highlight and confer the
significance of HvEXPB7 in root hair growth under drought stress in XZ5, and
provide a novel insight into the genetic basis for drought tolerance in Tibetan
wild barley.
PMID- 26417020
TI - Good and bad protons: genetic aspects of acidity stress responses in plants.
AB - Physiological aspects of acidity stress in plants (synonymous with H(+)
rhizotoxicity or low-pH stress) have long been a focus of research, in particular
with respect to acidic soils where aluminium and H(+) rhizotoxicities often co
occur. However, toxic H(+) and Al(3+) elicit different response mechanisms in
plants, and it is important to consider their effects separately. The primary aim
of this review was to provide the current state of knowledge regarding the
genetics of the specific reactions to low-pH stress in growing plants. A
comparison of the results gleaned from quantitative trait loci analysis and
global transcriptome profiling of plants in response to high proton
concentrations revealed a two-stage genetic response: (i) in the short-term,
proton pump H(+)-ATPases present the first barrier in root cells, allocating an
excess of H(+) into either the apoplast or vacuole; the ensuing defence signaling
system involves auxin, salicylic acid, and methyl jasmonate, which subsequently
initiate expression of STOP and DREB transcription factors as well as chaperone
ROF; (2) the long-term response includes other genes, such as alternative oxidase
and type II NAD(P)H dehydrogenase, which act to detoxify dangerous reactive
oxygen species in mitochondria, and help plants better manage the stress. A range
of transporter genes including those for nitrate (NTR1), malate (ALMT1), and
heavy metals are often up-regulated by H(+) rhizotoxicity. Expansins, cell-wall
related genes, the gamma-aminobutyric acid shunt and biochemical pH-stat genes
also reflect changes in cell metabolism and biochemistry in acidic conditions.
However, the genetics underlying the acidity stress response of plants is
complicated and only fragmentally understood.
PMID- 26417019
TI - Transcription factor StWRKY1 regulates phenylpropanoid metabolites conferring
late blight resistance in potato.
AB - Quantitative resistance is polygenically controlled and durable, but the
underlying molecular and biochemical mechanisms are poorly understood. Secondary
cell wall thickening is a critical process in quantitative resistance, regulated
by transcriptional networks. This paper provides compelling evidence on the
functionality of StWRKY1 transcription factor, in a compatible interaction of
potato-Phytophthora infestans, to extend our knowledge on the regulation of the
metabolic pathway genes leading to strengthening the secondary cell wall. A
metabolomics approach was used to identify resistance-related metabolites
belonging to the phenylpropanoid pathway and their biosynthetic genes regulated
by StWRKY1. The StWRKY1 gene in resistant potato was silenced to decipher its
role in the regulation of phenylpropanoid pathway genes to strengthen the
secondary cell wall. Sequencing of the promoter region of StWRKY1 in susceptible
genotypes revealed the absence of heat shock elements (HSEs). Simultaneous
induction of both the heat shock protein (sHSP17.8) and StWRKY1 following
pathogen invasion enables functioning of the latter to interact with the HSE
present in the resistant StWRKY1 promoter region. EMSA and luciferase transient
expression assays further revealed direct binding of StWRKY1 to promoters of
hydroxycinnamic acid amide (HCAA) biosynthetic genes encoding 4-coumarate:CoA
ligase and tyramine hydroxycinnamoyl transferase. Silencing of the StWRKY1 gene
was associated with signs of reduced late blight resistance by significantly
increasing the pathogen biomass and decreasing the abundance of HCAAs. This study
provides convincing evidence on the role of StWRKY1 in the regulation of
downstream genes to biosynthesize HCAAs, which are deposited to reinforce
secondary cell walls.
PMID- 26417021
TI - Transcriptome analysis of an apple (Malus * domestica) yellow fruit somatic
mutation identifies a gene network module highly associated with anthocyanin and
epigenetic regulation.
AB - Using RNA-seq, this study analysed an apple (Malus*domestica) anthocyanin
deficient yellow-skin somatic mutant 'Blondee' (BLO) and its red-skin parent
'Kidd's D-8' (KID), the original name of 'Gala', to understand the molecular
mechanisms underlying the mutation. A total of 3299 differentially expressed
genes (DEGs) were identified between BLO and KID at four developmental stages
and/or between two adjacent stages within BLO and/or KID. A weighted gene co
expression network analysis (WGCNA) of the DEGs uncovered a network module of 34
genes highly correlated (r=0.95, P=9.0*10(-13)) with anthocyanin contents.
Although 12 of the 34 genes in the WGCNA module were characterized and known of
roles in anthocyanin, the remainder 22 appear to be novel. Examining the
expression of ten representative genes in the module in 14 diverse apples
revealed that at least eight were significantly correlated with anthocyanin
variation. MdMYB10 (MDP0000259614) and MdGST (MDP0000252292) were among the most
suppressed module member genes in BLO despite being undistinguishable in their
corresponding sequences between BLO and KID. Methylation assay of MdMYB10 and
MdGST in fruit skin revealed that two regions (MR3 and MR7) in the MdMYB10
promoter exhibited remarkable differences between BLO and KID. In particular,
methylation was high and progressively increased alongside fruit development in
BLO while was correspondingly low and constant in KID. The methylation levels in
both MR3 and MR7 were negatively correlated with anthocyanin content as well as
the expression of MdMYB10 and MdGST. Clearly, the collective repression of the 34
genes explains the loss-of-colour in BLO while the methylation in MdMYB10
promoter is likely causal for the mutation.
PMID- 26417022
TI - High atmospheric carbon dioxide-dependent alleviation of salt stress is linked to
RESPIRATORY BURST OXIDASE 1 (RBOH1)-dependent H2O2 production in tomato (Solanum
lycopersicum).
AB - Plants acclimate rapidly to stressful environmental conditions. Increasing
atmospheric CO2 levels are predicted to influence tolerance to stresses such as
soil salinity but the mechanisms are poorly understood. To resolve this issue,
tomato (Solanum lycopersicum) plants were grown under ambient (380 MUmol mol(-1))
or high (760 MUmol mol(-1)) CO2 in the absence or presence of sodium chloride
(100mM). The higher atmospheric CO2 level induced the expression of RESPIRATORY
BURST OXIDASE 1 (SlRBOH1) and enhanced H2O2 accumulation in the vascular cells of
roots, stems, leaf petioles, and the leaf apoplast. Plants grown with higher CO2
levels showed improved salt tolerance, together with decreased leaf transpiration
rates and lower sodium concentrations in the xylem sap, vascular tissues, and
leaves. Silencing SlRBOH1 abolished high CO2 -induced salt tolerance and
increased leaf transpiration rates, as well as enhancing Na(+) accumulation in
the plants. The higher atmospheric CO2 level increased the abundance of a subset
of transcripts involved in Na(+) homeostasis in the controls but not in the
SlRBOH1-silenced plants. It is concluded that high atmospheric CO2 concentrations
increase salt stress tolerance in an apoplastic H2O2 dependent manner, by
suppressing transpiration and hence Na(+) delivery from the roots to the shoots,
leading to decreased leaf Na(+) accumulation.
PMID- 26417023
TI - Kranz and single-cell forms of C4 plants in the subfamily Suaedoideae show
kinetic C4 convergence for PEPC and Rubisco with divergent amino acid
substitutions.
AB - The two carboxylation reactions performed by phosphoenolpyruvate carboxylase
(PEPC) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) are vital in
the fixation of inorganic carbon for C4 plants. The abundance of PEPC is
substantially elevated in C4 leaves, while the location of Rubisco is restricted
to one of two chloroplast types. These differences compared with C3 leaves have
been shown to result in convergent enzyme optimization in some C4 species.
Investigation into the kinetic properties of PEPC and Rubisco from Kranz C4,
single cell C4, and C3 species in Chenopodiaceae s. s. subfamily Suaedoideae
showed that these major carboxylases in C4 Suaedoideae species lack the same
mutations found in other C4 systems which have been examined; but still have
similar convergent kinetic properties. Positive selection analysis on the N
terminus of PEPC identified residues 364 and 368 to be under positive selection
with a posterior probability >0.99 using Bayes empirical Bayes. Compared with
previous analyses on other C4 species, PEPC from C4 Suaedoideae species have
different convergent amino acids that result in a higher K m for PEP and malate
tolerance compared with C3 species. Kinetic analysis of Rubisco showed that C4
species have a higher catalytic efficiency of Rubisco (k catc in mol CO2 mol(-1)
Rubisco active sites s(-1)), despite lacking convergent substitutions in the rbcL
gene. The importance of kinetic changes to the two-carboxylation reactions in C4
leaves related to amino acid selection is discussed.
PMID- 26417024
TI - Interleukin 21 and Its Receptor Play a Role in Proliferation, Migration and
Invasion of Breast Cancer Cells.
AB - Interleukin 21 (IL21) is a cytokine produced predominantly by cluster of
differentiation 4 (CD4+) T-cells and natural killer T-cells. There exists
evidence that IL21 is implicated in various immunological processes through its
specific receptor (IL21R). However, the participation of IL21 in the pathogenesis
of solid tumors is not fully conclusive. In the present study, we demonstrated
that there was differential expression of IL21R in breast cancer cells using
reverse transcription-polymerase chain reaction (RT-PCR), western blotting and
sequence analysis. The expression of IL21R was stronger in MDA-231 cells, weaker
in MCF7 but negative in ZR-75.1 cells. The invasion and migratory capacity of
IL21R+ MDA-231 cells was enhanced by IL21 in a dose-dependent manner. After IL21R
was knocked-down by siRNA gene silencing, the response of MDA-231 to treatment
with IL21 was attenuated. We found that siRNA silencing of IL21R also
spontaneously suppressed cell proliferation. However, IL21 had no additional
effect on the proliferation of MDA-231 cells. We also found that IL21R was
involved in signaling pathways of matrix metalloproteinases (MMPs), that are
crucial for spreading and migration of metastatic MDA231 cells. In conclusion, we
unveiled the roles of IL21R in breast cancer cells, which enhances our knowledge
on immunological regulation of cancer cells through the axis of IL21 and its
receptor.
PMID- 26417025
TI - Circulating Messenger RNA Profiling with Microarray and Next-generation
Sequencing: Cross-platform Comparison.
AB - BACKGROUND: Circulating mRNA is a less invasive and more easily accessed source
of samples for biomedical research and clinical applications. However, it is of
poor quality. We explored and compared the ability of two high-throughput
platforms for the profiling of circulating mRNA regarding their ability to
retrieve useful information out of this type of samples. MATERIALS AND METHODS:
Circulating mRNAs from three non-small cell lung cancer patients and three
healthy controls were analyzed by the cDNA-mediated annealing, selection,
extension, and ligation (DASL) assay and high-throughput RNA sequencing (RSEQ).
Twelve genes were selected for further confirmation by reverse transcription
quantitative polymerase chain reaction (RT-qPCR). RESULTS: The overall expression
profiles derived from the two platforms showed modest-to-moderate correlation.
Genes with higher expression levels had higher cross-platform concordance than
those of medium- and low-expression levels. In addition, the pathway signatures
identified by gene set enrichment analysis from both platforms were in agreement.
The RT-q PCR results for the selected genes correlated well with that of RSEQ.
CONCLUSION: Genes with higher expression levels have cross-platform concordance
and can be potential biomarkers. Furthermore, RSEQ is a better tool for profiling
circulating mRNAs.
PMID- 26417027
TI - Interleukin-24 (IL-24) Expression and Biological Impact on HECV Endothelial
Cells.
AB - BACKGROUND: IL-24, also termed MDA-7, is a member of the IL-10 family of
cytokines. IL-24 is reported to be expressed in a series of cell lines, including
keratinocytes as well as breast, lung and prostate cancer cells, but was
primarily found in a human melanoma cell line. IL-24 is suggested to have many
biological properties displaying anti-tumour effects via induction of apoptosis,
suppressing proliferation, invasion and metastasis of cancer cells. IL-24 has
also been reported to inhibit the migration of cancer cells and keratinocytes,
and have anti-angiogeneic properties. The biological functions of IL-24 are
regulated through both autocrine and paracrine methods. However, currently there
exists little knowledge regarding the effect of IL-24 on endothelial cell
biology. MATERIALS AND METHODS: The impact of rhIL-24 on human endothelial HECV
cell growth, migration, trans-endothelial resistance and angiogenic potential was
examined using cellular functional assays. Additionally, the relationship between
IL-24 and a number of cell junction proteins were examined using
immunofluorescence staining. RESULTS: IL-24 and receptor molecules was found to
be expressed in HECV endothelial cells. Treatment of this cell line with rhIL-24
was found to promote cell migration rates and suppress tubule formation.
CONCLUSION: Treatment of HECV cells with rhIL-24 can promote migration and
inhibit tubule formation but does not impact cell growth or permeability at the
tested concentrations. Potential links between IL-24 and AKT or PLCgamma-related
pathways with regard to these effects are also presented in the present study.
PMID- 26417026
TI - Gene-expression Profiling in Non-small Cell Lung Cancer with Invasion of
Mediastinal Lymph Nodes for Prognosis Evaluation.
AB - BACKGROUND/AIM: The aim of the study was to determine the pathways and expression
profile of the genes that might predict response to neoadjuvant chemotherapy in
patients with stage IIIA non-small cell lung cancer (NSCLC). MATERIALS AND
METHODS: We evaluated, by microarray, the gene-expression profile of tumoral
mediastinal lymph node samples surgically removed from 27 patients with stage
IIIA NSCLC before neoadjuvant chemotherapy treatment. Depending on the response
to the induction treatment, the patients were divided in two groups: group A:
patients whose disease evolved, stabilized or who had minor response to
chemotherapy, and group B: patients whose disease stabilized or had major
response to chemotherapy. RESULTS: The microarray experiments identified 1,127
genes with a modified expression in the tumoral tissue compared to normal tissue
with p<=0.05 and 44 genes with p<=0.01. The identified up-regulated genes between
tumoral versus normal tissue included collagen, type I, alpha 1 (COL1A1), inhibin
beta A (INHBA) and thioredoxin interacting protein (TXNIP). Pathways identified
with a false-discovery rate of <0.005 included: cytokine pathways, focal adhesion
or extracellular matrix receptor interaction. CONCLUSION: Our approach identified
important characteristics of NSCLC and pointed-out molecular differences between
sub-groups of patients based on their response to therapy.
PMID- 26417028
TI - Comparative Proteomics of Tumor and Paired Normal Breast Tissue Highlights
Potential Biomarkers in Breast Cancer.
AB - BACKGROUND/AIM: Breast cancer is the most common type of cancer among women
worldwide, and about 57,000 new cases are expected for the Brazilian population
in 2015. Elucidation of protein expression and modification is essential for the
biological understanding, early diagnosis and therapeutics of breast cancer. The
main objectives of the study are comparison between the proteome of tumor and
paired non-tumor breast cancer tissues, describing all identified proteins,
highlighting the ones most differentially expressed and comparing the data with
existing literature. MATERIALS AND METHODS: The five paired samples from patients
with invasive ductal carcinoma were analyzed by 2-DE and MS. RESULTS: We
collected 161 identified spots corresponding to 110 distinct proteins. Forty
three differentially-expressed spots were common to at least two samples, and the
ten proteins with the highest-fold changes were CASPE, ENOG, TPM1, CAPG, VIME,
TPM3, TRFE, PDIA6, WDR61 and PDIA3. Metabolic enzymes and proteins with binding
functions were the most representative functional classes of proteins with
increased and decreased expression in tumor tissue respectively. CONCLUSION:
Taking the fold change as a parameter, we point to future targets to be studied
by functional methods in a search for biomarkers for initiation and progress of
breast cancer.
PMID- 26417029
TI - Impact of PTEN IVS4 Polymorphism (rs3830675) on Cancer Susceptibility: An Updated
Meta-analysis.
AB - BACKGROUND/AIM: Phosphatase and tensin homolog (PTEN) acts as a tumor suppressor
gene through the action of its phosphatase protein product. We performed a meta
analysis to evaluate their relationship. MATERIALS AND METHODS: A comprehensive
database search was performed. Odds ratios (OR) with 95% confidence intervals
(CI) were calculated to assess the association between PTEN IVS4 polymorphism and
cancer. RESULTS: The meta-analysis indicated that PTEN IVS4 (-/-) genotype was
significantly associated with the risk of cancer (OR=1.47, 95% CI=1.11-1.84),
especially for digestive cancer (OR=1.67, 95% CI=1.28-2.18) compared to the (+/+)
genotype. Moreover, the (-) allele of PTEN IVS4 polymorphism was also
significantly associated with the risk of cancer (OR=1.27, 95% CI=1.14-1.41),
especially for digestive cancer (OR=1.42, 95% CI=1.16-1.74) compared to the (+)
allele. No significant association was observed between PTEN IVS4 (+/-) genotype
and risk of cancer. CONCLUSION: PTEN IVS4 (-/-) genotype was significantly
associated with increased risk of cancer especially for digestive tract cancer
compared to the (+/+) genotype. A similar phenomenon was observed in the (-)
allele of PTEN IVS4 polymorphism compared to the (+) allele and the recessive
effect model.
PMID- 26417031
TI - Correction.
PMID- 26417032
TI - Genomic Surveillance Elucidates Persistent Wild Poliovirus Transmission During
2013-2015 in Major Reservoir Areas of Pakistan.
AB - BACKGROUND: Despite tremendous efforts in the fight against polio, Pakistan bears
the highest proportion of poliomyelitis cases among the 3 endemic countries
including Afghanistan and Nigeria. Apart from insecurity and inaccessibility
challenges, the substantial shift of unimmunized children from North Waziristan
due to recent military operations was presumed to favor the widespread poliovirus
infection in Pakistan. METHODS: To better understand the current epidemiological
situation, we analyzed the virologic data of wild poliovirus type 1 (WPV1)
strains detected in Pakistan during 2013-2015. RESULTS: Five genetic clusters (A
E) were identified with at least 5% nucleotide divergence in the viral protein 1
(VP1) coding region. Peshawar, Quetta, and Karachi were found to be the major
endemic foci where multiple discrete genetic lineages of WPV1 were detected.
Phylogenetic analysis suggests that wild poliovirus strains from endemic regions
were genetically distant (with 5%-15% VP1 nucleotide divergence) from those
detected in North Waziristan cases, excluding the possibility of a recent
progenitor of WPV1 instigating single-source transmission across the country.
Orphan lineages detected in Rawalpindi, Lahore, Hyderabad, Sukkur, and Jacobabad
revealed silent transmission and the need for vigilant surveillance. Sustenance
of analogous genetic lineages over a period of 3 years highlights multiple
unimmunized foci present to maintain viral genetic diversity. CONCLUSIONS: Our
findings are inconsistent with the hypothesis that impoverished populations from
North Waziristan serve as a possible determinant of widespread poliomyelitis
infection in Pakistan and further emphasize the need to scale-up clinical and
environmental surveillance as well as immunization activities.
PMID- 26417033
TI - Poliomyelitis in Pakistan.
PMID- 26417034
TI - All-Cause Mortality and Progression Risks to Hepatic Decompensation and
Hepatocellular Carcinoma in Patients Infected With Hepatitis C Virus.
AB - BACKGROUND: A key question in care of patients with chronic hepatitis C virus
(HCV) infection is beginning treatment immediately vs delaying treatment. Risks
of mortality and disease progression in "real world" settings are important to
assess the implications of delaying HCV treatment. METHODS: This was a cohort
study of HCV patients identified from 4 integrated health systems in the United
States who had liver biopsies during 2001-2012. The probabilities of death and
progression to hepatocellular carcinoma, hepatic decompensation (hepatic
encephalopathy, esophageal varices, ascites, or portal hypertension) or liver
transplant were estimated over 1, 2, or 5 years by fibrosis stage (Metavir F0-F4)
determined by biopsy at beginning of observation. RESULTS: Among 2799 HCV
monoinfected patients who had a qualifying liver biopsy, the mean age at the time
of biopsy was 50.7 years. The majority were male (58.9%) and non-Hispanic white
(66.9%). Over a mean observation of 5.0 years, 261 (9.3%) patients died and 34
(1.2%) received liver transplants. At 5 years after biopsy, the estimated risk of
progression to hepatic decompensation or hepatocellular carcinoma was 37.2% in
stage F4, 19.6% in F3, 4.7% in F2, and 2.3% in F0-F1 patients. Baseline biopsy
stage F3 or F4 and platelet count below normal were the strongest predictors of
progression to hepatic decompensation or hepatocellular carcinoma. CONCLUSIONS:
The risks of death and progression to liver failure varied greatly by fibrosis
stage. Clinicians and policy makers could use these progression risk data in
prioritization and in determining the timing of treatment for patients in early
stages of liver disease.
PMID- 26417035
TI - Susceptibility Loci for Clinical Coronary Artery Disease and Subclinical Coronary
Atherosclerosis Throughout the Life-Course.
AB - BACKGROUND: Recent genome-wide association studies have identified 49 single
nucleotide polymorphisms associated with clinical coronary artery disease. The
mechanism by which these loci influence risk remains largely unclear. METHODS AND
RESULTS: We examined the association between a genetic risk score composed of
high-risk alleles at the 49 single nucleotide polymorphisms and the degree of
subclinical coronary atherosclerosis in 7798 participants from 6 studies
stratified into 4 age groups at the time of assessment (15-34, 35-54, 55-74, and
>75 years). Atherosclerosis was quantified by staining and direct visual
inspection of the right coronary artery in the youngest group and by scanning for
coronary artery calcification in the remaining groups. We defined cases as
subjects within the top quartile of degree of atherosclerosis in 3 groups and as
subjects with a coronary artery calcium score >0 in the fourth (35-54 years)
where less than one quarter had any coronary artery calcium. In our meta-analysis
of all strata, we found 1-SD increase in the genetic risk score increased the
risk of advanced subclinical coronary atherosclerosis by 36% (P=8.3*10(-25)).
This increase in risk was significant in all 4 age groups including the youngest
group where atherosclerosis consisted primarily of raised lesions without
macroscopic evidence of plaque rupture or thrombosis. Results were similar when
we restricted the genetic risk score to 32 single nucleotide polymorphisms not
associated with traditional risk factors or when we adjusted for traditional risk
factors. CONCLUSIONS: A genetic risk score for clinical coronary artery disease
is associated with advanced subclinical coronary atherosclerosis throughout the
life-course. This association is apparent even at the earliest, uncomplicated
stages of atherosclerosis.
PMID- 26417036
TI - The Frequency, Characteristics, and Outcomes Among Cancer Patients With Delirium
Admitted to an Acute Palliative Care Unit.
AB - BACKGROUND: Delirium is a common neuropsychiatric condition seen in patients with
severe illness, such as advanced cancer. Few published studies are available of
the frequency, course, and outcomes of standardized management of delirium in
advanced cancer patients admitted to acute palliative care unit (APCU). In this
study, we examined the frequency, characteristics, and outcomes of delirium in
patients with advanced cancer admitted to an APCU. METHODS: Medical records of
609 consecutive patients admitted to the APCU from January 2011 through December
2011 were reviewed. Data on patients' demographics; Memorial Delirium Assessment
Scale (MDAS) score; palliative care specialist (PCS) diagnosis of delirium;
delirium etiology, subtype, and reversibility; late development of delirium; and
discharge outcome were collected. Delirium was diagnosed with MDAS score >=7 and
by a PCS using Diagnostic and Statistical Manual, 4th edition, Text Revision
criteria. All patients admitted to the APCU received standardized assessments and
management of delirium per best practice guidelines in delirium management.
RESULTS: Of 556 patients in the APCU, 323 (58%) had a diagnosis of delirium. Of
these, 229 (71%) had a delirium diagnosis on admission and 94 (29%) developed
delirium after admission to the APCU. Delirium reversed in 85 of 323 episodes
(26%). Half of patients with delirium (n = 162) died. Patients with the diagnosis
of delirium had a lower median overall survival than those without delirium.
Patients who developed delirium after admission to the APCU had poorer survival
(p <= .0001) and a lower rate of delirium reversal (p = .03) compared with those
admitted with delirium. CONCLUSION: More than half of the patients admitted to
the APCU had delirium. Reversibility occurred in almost one-third of cases.
Diagnosis of delirium was associated with poorer survival.
PMID- 26417038
TI - Exploring Knowledge, Attitudes, and Practices Related to Breast and Cervical
Cancers in Mongolia: A National Population-Based Survey.
AB - BACKGROUND: Mongolia bears the second-highest cancer burden in the world (5,214
disability-adjusted life years per 100,000 people, age standardized). To
determine drivers of the growing burden of noncommunicable diseases, including
breast and cervical cancers, a national knowledge, attitudes, and practices (KAP)
survey was implemented in 2010. METHODS: This paper analyzed the results of the
2010 KAP survey, which sampled 3,450 households nationally. Reflecting Mongolian
screening policies, women aged 30 and older were included in analyses of
questions regarding breast and cervical cancer (n = 1,193). Univariate and
multivariate odds ratios (MORs) were derived through logistic regression to
determine associations between demographic covariables (residence, age,
education, employment) and survey responses. RESULTS: This study found that 25.7%
(95% confidence interval [CI]: 23.3-28.3) and 22.1% (95% CI: 19.8-24.5) of female
participants aged 30 years or older self-rated their knowledge of breast and
cervical cancers, respectively, as "none." Employment and education were
associated with greater awareness of both cancers and participation in screening
examinations (p < .05). Clinical breast examinations were more common among rural
than urban participants (MOR: 1.492; 95% CI: 1.125-1.979). Of all female
participants, 17% (95% CI: 15.3-18.5) knew that cervical cancer is vaccine
preventable. CONCLUSION: Our results suggest that cancer control in Mongolia
should emphasize health education, particularly among lower-educated, rural, and
unemployed women. The health infrastructure should be strengthened to reflect
rural to urban migration. Finally, although there is awareness that early
detection improves outcomes, a significant proportion of women do not engage in
screening. These trends warrant further research on barriers and solutions.
IMPLICATIONS FOR PRACTICE: The rising burden of breast and cervical cancers,
particularly in low- and middle-income countries, necessitates the development of
effective strategies for cancer control. This paper examines barriers to health
service use in Mongolia, a country with a high cancer burden. The 2010 national
knowledge, attitude and practices survey data indicate that cancer control
efforts should focus on improving health education among lower-educated, rural,
and unemployed populations, who display the least knowledge of breast and
cervical cancers. Moreover, the findings support the need to emphasize individual
risk for disease in cancer education and ensure that the health-care
infrastructure reflects Mongolia's urbanization.
PMID- 26417037
TI - Attitudes and Beliefs Toward Supportive and Palliative Care Referral Among
Hematologic and Solid Tumor Oncology Specialists.
AB - BACKGROUND: Palliative care (PC) referrals are often delayed for patients with
hematologic malignancies. We examined the differences in attitudes and beliefs
toward PC referral between hematologic and solid tumor specialists and how their
perception changed with use of the service name "supportive care" (SC). MATERIALS
AND METHODS: We randomly surveyed 120 hematologic and 120 solid tumor oncology
specialists at our tertiary care cancer center to examine their attitudes and
beliefs toward PC and SC referral. RESULTS: Of the 240 specialists, 182 (76%)
responded. Compared with solid tumor specialists, hematologic specialists were
less likely to report that they would refer symptomatic patients with newly
diagnosed cancer to PC (solid tumor, 43% vs. hematology, 21%; p = .002). A
significantly greater proportion of specialists expressed that they would refer a
patient with newly diagnosed cancer to SC than PC (solid tumor specialists: SC,
81% vs. PC, 43%; p < .001; hematology specialists: SC, 66% vs. PC, 21%; p <
.001). The specialists perceived that PC was more likely than SC to be a barrier
for referral (PC, 36% vs. SC, 3%; p < .001), to be synonymous with hospice (PC,
53% vs. SC, 6%; p < .001), to decrease hope (PC, 58% vs. SC, 8%; p < .001), and
to be less appropriate for treatment of chemotherapy side effects (PC, 64% vs.
SC, 19%; p < .001). On multivariate analysis, female clinicians (odds ratio [OR],
4.5; 95% confidence interval [CI], 1.3-15.2; p = .02) and the perception that PC
is a barrier for referral (OR, 3.0; 95% CI, 1.2-7.6; p = .02) were associated
with PC referral if the service name "SC" was used. CONCLUSION: Hematologic
specialists were less likely to refer patients early in the disease trajectory
and were conducive to referral with the service name SC instead of PC.
IMPLICATIONS FOR PRACTICE: The present survey of oncology specialists found that
hematologic specialists were less likely than solid tumor specialists to report
that they would refer symptomatic patients with newly diagnosed cancer to
palliative care. However, both groups were significantly more willing to refer
patients early in the disease trajectory if the service name "supportive care"
were used instead of "palliative care." These findings suggest that rebranding
might help to overcome the stigma associated with palliative care and improve
patient access to palliative care services.
PMID- 26417039
TI - Outpatient Intraperitoneal Catumaxomab Therapy for Malignant Ascites Related to
Advanced Gynecologic Neoplasms.
AB - BACKGROUND: Catumaxomab (CATU) is a trifunctional antibody approved for
intraperitoneal (i.p.) treatment of malignant ascites (MA) related to carcinomas
expressing the epithelial cell-adhesion molecule (EpCAM). CATU is mostly given to
hospitalized patients, although outpatient treatment seems appropriate in
selected individuals. This observational trial sought to obtain more detailed
information regarding the feasibility of CATU in outpatients with MA related to
various gynecologic tumors, including epithelial ovarian (EOC) and metastatic
breast cancer (MBC). MATERIALS AND METHODS: A total of 30 patients were included,
17 with EOC, 7 with MBC, and 6 with other malignancies. The patients had failed a
median of 5 (range 1-12) previous systemic treatments. CATU was administered via
an indwelling i.p. catheter at four increasing doses (i.e., 10, 20, 50, and 150
ug) given at 4-day intervals over 2 weeks. Toxicities were scored according to
the Common Terminology Criteria for Adverse Events, version 4.03. Puncture-free
survival (PuFS) was calculated from the start of CATU until the next puncture for
MA, death, or loss to follow-up. Overall survival (OS) was calculated from the
start of CATU to death from any reason or loss to follow-up. We also investigated
various clinical parameters to predict PuFS and OS. These included age, tumor
type, performance status, intensity of pretreatment, presence of extraperitoneal
metastases, relative lymphocyte count at baseline, patient adherence to therapy,
and the patients' ability to undergo systemic treatment after CATU. RESULTS: CATU
was exclusively given on an outpatient basis, and 19 patients (63.3%) received
all four planned i.p. instillations. Toxicity was the reason for discontinuation
in only 2 patients. Toxicity was generally manageable, with abdominal pain,
nausea/vomiting, fatigue, and fever the predominant adverse effects. Secondary
hospitalization was necessary for 7 patients (23.3%), with a general deteriorated
condition in 5 and fever/infection or abdominal pain in 1 patient each.
Subsequent systemic treatment was possible in 11 patients (36.7%). Only 5
patients (16.7%) required a second puncture after i.p. CATU. The median PuFS was
56 days, and the median OS was 79.5 days. Positive predictors of both PuFS and OS
were performance status, absence of extraperitoneal tumor, the capability to
receive all four CATU infusions, and the ability to undergo subsequent systemic
treatment. CONCLUSION: Outpatient i.p. CATU therapy for MA related to various
gynecologic carcinomas is safe and effective in producing good ascites control in
most individuals, allowing for subsequent systemic therapy in a substantial
proportion of patients. IMPLICATIONS FOR PRACTICE: Intraperitoneal treatment with
the trifunctional antibody catumaxomab (CATU) was possible in a selected
population of 30 outpatients with malignant ascites due to epithelial female
genital tract or breast carcinoma. Toxicity was largely manageable. Patients in
good condition at baseline, without extraperitoneal tumor and/or liver
metastases, and with the ability to complete all four planned CATU instillations
and the capability of undergoing subsequent systemic therapy benefited the most
in terms of both puncture-free and overall survival. Outpatient i.p. CATU is safe
and effective in a selected group of patients with malignant ascites due to
various gynecologic malignancies and could be cost-saving compared with an
inpatient approach.
PMID- 26417040
TI - Facial whisker pattern is not sufficient to instruct a whisker-related
topographic map in the mouse somatosensory brainstem.
AB - Facial somatosensory input is relayed by trigeminal ganglion (TG) neurons and
serially wired to brainstem, thalamus and cortex. Spatially ordered sets of
target neurons generate central topographic maps reproducing the spatial
arrangement of peripheral facial receptors. Facial pattern provides a necessary
template for map formation, but may be insufficient to impose a brain somatotopic
pattern. In mice, lower jaw sensory information is relayed by the trigeminal
nerve mandibular branch, whose axons target the brainstem dorsal principal
sensory trigeminal nucleus (dPrV). Input from mystacial whiskers is relayed by
the maxillary branch and forms a topographic representation of rows and whiskers
in the ventral PrV (vPrV). To investigate peripheral organisation in imposing a
brain topographic pattern, we analysed Edn1(-/-) mice, which present ectopic
whisker rows on the lower jaw. We found that these whiskers were innervated by
mandibular TG neurons which initially targeted dPrV. Unlike maxillary TG neurons,
the ectopic whisker-innervating mandibular neuron cell bodies and pre-target
central axons did not segregate into a row-specific pattern nor target the dPrV
with a topographic pattern. Following periphery-driven molecular repatterning to
a maxillary-like identity, mandibular neurons partially redirected their central
projections from dPrV to vPrV. Thus, while able to induce maxillary-like
molecular features resulting in vPrV final targeting, a spatially ordered lower
jaw ectopic whisker pattern is insufficient to impose row-specific pre-target
organisation of the central mandibular tract or a whisker-related matching
pattern of afferents in dPrV. These results provide novel insights into periphery
dependent versus periphery-independent mechanisms of trigeminal ganglion and
brainstem patterning in matching whisker topography.
PMID- 26417043
TI - De novo DNA methylation through the 5'-segment of the H19 ICR maintains its
imprint during early embryogenesis.
AB - Genomic imprinting is a major monoallelic gene expression regulatory mechanism in
mammals, and depends on gamete-specific DNA methylation of specialized cis
regulatory elements called imprinting control regions (ICRs). Allele-specific DNA
methylation of the ICRs is faithfully maintained at the imprinted loci throughout
development, even in early embryos where genomes undergo extensive epigenetic
reprogramming, including DNA demethylation, to acquire totipotency. We previously
found that an ectopically introduced H19 ICR fragment in transgenic mice acquired
paternal allele-specific methylation in the somatic cells of offspring, whereas
it was not methylated in sperm, suggesting that its gametic and postfertilization
modifications were separable events. We hypothesized that this latter activity
might contribute to maintenance of the methylation imprint in early embryos.
Here, we demonstrate that methylation of the paternally inherited transgenic H19
ICR commences soon after fertilization in a maternal DNMT3A- and DNMT3L-dependent
manner. When its germline methylation was partially obstructed by insertion of
insulator sequences, the endogenous paternal H19 ICR also exhibited
postfertilization methylation. Finally, we refined the responsible sequences for
this activity in transgenic mice and found that deletion of the 5' segment of the
endogenous paternal H19 ICR decreased its methylation after fertilization and
attenuated Igf2 gene expression. These results demonstrate that this segment of
the H19 ICR is essential for its de novo postfertilization DNA methylation, and
that this activity contributes to the maintenance of imprinted methylation at the
endogenous H19 ICR during early embryogenesis.
PMID- 26417041
TI - Excitability governs neural development in a hippocampal region-specific manner.
AB - Neuronal activity, including intrinsic neuronal excitability and synaptic
transmission, is an essential regulator of brain development. However, how the
intrinsic neuronal excitability of distinct neurons affects their integration
into developing circuits remains poorly understood. To investigate this problem,
we created several transgenic mouse lines in which intrinsic excitability is
suppressed, and the neurons are effectively silenced, in different excitatory
neuronal populations of the hippocampus. Here we show that CA1, CA3 and dentate
gyrus neurons each have unique responses to suppressed intrinsic excitability
during circuit development. Silenced CA1 pyramidal neurons show altered spine
development and synaptic transmission after postnatal day 15. By contrast,
silenced CA3 pyramidal neurons seem to develop normally. Silenced dentate granule
cells develop with input-specific decreases in spine density starting at
postnatal day 11; however, a compensatory enhancement of neurotransmitter release
onto these neurons maintains normal levels of synaptic activity. The synaptic
changes in CA1 and dentate granule neurons are not observed when synaptic
transmission, rather than intrinsic excitability, is blocked in these neurons.
Thus, our results demonstrate a crucial role for intrinsic neuronal excitability
in establishing hippocampal connectivity and reveal that neuronal development in
each hippocampal region is distinctly regulated by excitability.
PMID- 26417042
TI - ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal
mesoderm.
AB - The secreted glycoprotein sonic hedgehog (Shh) is expressed in the prechordal
mesoderm, where it plays a crucial role in induction and patterning of the
ventral forebrain. Currently little is known about how Shh is regulated in
prechordal tissue. Here we show that in the embryonic chick, Shh is expressed
transiently in prechordal mesoderm, and is governed by unprocessed Nodal.
Exposure of prechordal mesoderm microcultures to Nodal-conditioned medium, the
Nodal inhibitor CerS, or to an ALK4/5/7 inhibitor reveals that Nodal is required
to maintain both Shh and Gsc expression, but whereas Gsc is largely maintained
through canonical signalling, Nodal signals through a non-canonical route to
maintain Shh. Further, Shh expression can be maintained by a recombinant Nodal
cleavage mutant, proNodal, but not by purified mature Nodal. A number of lines of
evidence suggest that proNodal acts via FGFR3. ProNodal and FGFR3 co
immunoprecipitate and proNodal increases FGFR3 tyrosine phosphorylation. In
microcultures, soluble FGFR3 abolishes Shh without affecting Gsc expression.
Further, prechordal mesoderm cells in which Fgfr3 expression is reduced by Fgfr3
siRNA fail to bind to proNodal. Finally, targeted electroporation of Fgfr3 siRNA
to prechordal mesoderm in vivo results in premature Shh downregulation without
affecting Gsc. We report an inverse correlation between proNodal-FGFR3 signalling
and pSmad1/5/8, and show that proNodal-FGFR3 signalling antagonises BMP-mediated
pSmad1/5/8 signalling, which is poised to downregulate Shh. Our studies suggest
that proNodal/FGFR3 signalling governs Shh duration by repressing canonical BMP
signalling, and that local BMPs rapidly silence Shh once endogenous Nodal-FGFR3
signalling is downregulated.
PMID- 26417044
TI - Genome-wide assessment of differential effector gene use in embryogenesis.
AB - Six different populations of cells were isolated by fluorescence-activated cell
sorting from disaggregated late blastula- and gastrula-stage sea urchin embryos
according to the regulatory states expressed in these cells, as reported by
recombineered bacterial artificial chromosomes producing fluorochromes.
Transcriptomes recovered from these embryonic cell populations revealed striking,
early differential expression of large cohorts of effector genes. The six cell
populations were presumptive pigment cells, presumptive neurogenic cells,
presumptive skeletogenic cells, cells from the stomodeal region of the oral
ectoderm, ciliated band cells and cells from the endoderm/ectoderm boundary that
will give rise both to hindgut and to border ectoderm. Transcriptome analysis
revealed that each of these domains specifically expressed several hundred
effector genes at significant levels. Annotation indicated the qualitative
individuality of the functional nature of each cell population, even though they
were isolated from embryos only 1-2 days old. In no case was more than a tiny
fraction of the transcripts enriched in one population also enriched in any other
of the six populations studied. As was particularly clear in the cases of the
presumptive pigment, neurogenic and skeletogenic cells, all three of which
represent precociously differentiating cell types of this embryo, most
specifically expressed genes of given cell types are not significantly expressed
at all in the other cell types. Thus, at the effector gene level, a dramatic,
cell type-specific pattern of differential gene regulation is established well
before any significant embryonic morphogenesis has occurred.
PMID- 26417045
TI - Leflunomide Induces Pulmonary and Hepatic CYP1A Enzymes via Aryl Hydrocarbon
Receptor.
AB - Emerging evidence indicates that the aryl hydrocarbon receptor (AhR) plays a
crucial role in normal physiologic homeostasis. Additionally, aberrant AhR
signaling leads to several pathologic states in the lung and liver. Activation of
AhR transcriptionally induces phase I (CYP1A) detoxifying enzymes. Although the
effects of the classic AhR ligands such as 3-methylcholanthrene and dioxins on
phase 1 enzymes are well studied in rodent lung, liver, and other organs, the
toxicity profiles limit their use as therapeutic agents in humans. Hence, there
is a need to identify and investigate nontoxic AhR ligands not only to understand
the AhR biology but also to develop the AhR as a clinically relevant therapeutic
target. Leflunomide is a Food and Drug Administration-approved drug in humans
that is known to have AhR agonist activity in vitro. Whether it activates AhR and
induces phase 1 enzymes in vivo is unknown. Therefore, we tested the hypothesis
that leflunomide will induce pulmonary and hepatic CYP1A enzymes in C57BL/6J wild
type mice, but not in AhR-null mice. We performed real-time reverse-transcription
polymerase chain reaction analyses for CYP1A1/2 mRNA expression, western blot
assays for CYP1A1/2 protein expression, and ethoxyresorufinO-deethylase assay for
CYP1A1 catalytic activity. Leflunomide increased CYP1A1/A2 mRNA, protein, and
enzymatic activities in wild-type mice. In contrast, leflunomide failed to
increase pulmonary and hepatic CYP1A enzymes in AhR-null mice. In conclusion, we
provide evidence that leflunomide induces pulmonary and hepatic CYP1A enzymes via
the AhR.
PMID- 26417046
TI - A Multicentre Evaluation of Risk Factors for Anastomotic Leakage After
Restorative Proctocolectomy with Ileal Pouch-Anal Anastomosis for Inflammatory
Bowel Disease.
AB - BACKGROUND: Anastomotic leakage is a major complication after restorative
proctocolectomy with ileal pouch-anal anastomosis [IPAA]. Identification of
patients at high risk of leakage may influence surgical decision making. The aim
of this study was to identify risk factors associated with anastomotic leakage
after restorative proctocolectomy with IPAA. METHODS: Between September 1990 and
January 2015, patients who underwent IPAA for inflammatory bowel disease [IBD]
were identified from prospectively maintained databases of three tertiary
referral centres. Retrospective chart review identified additional data on
demographic and surgical variables. Multivariable regression models were
developed to identify risk factors for anastomotic leakage. Separate analyses
were performed for type of procedure. RESULTS: A total of 640 patients [56.9%
male] were included, with a median age of 38 years [interquartile range 29-48];
96 [15.0%] patients developed anastomotic leakage. Multivariable regression
analysis demonstrated that being overweight (body mass index [BMI] > 25], (odds
ratio [OR] 1.92; 95% confidence interval [CI] 1.15 - 3.18), and American Society
of Anesthesiologists classification [ASA score > 2] [OR 1.91; 95% CI 1.03 - 3.54]
were independent risk factors for anastomotic leakage in patients who underwent a
completion proctectomy. A disease course of > 5 years [OR 2.34; 95% CI 1.42 -
3.87] and concurrent combination of anti-tumour necrosis factor [TNF] and
steroids [OR 6.40; 95% CI 1.76 - 23.20] were independent risk factors for
anastomotic leakage in patients who underwent a proctocolectomy and IPAA.
CONCLUSIONS: Independent risk factors for anastomotic leakage in IBD patients
undergoing IPAA are BMI >25, ASA score >2, disease course > 5 years, and
concurrent steroid and anti-TNF treatment, with a different risk profile for one
stage proctocolectomy and completion proctectomy procedures.
PMID- 26417047
TI - Reintroduction of Anti-TNFalpha Therapy After (or even During) Anti-TNFalpha
associated Tuberculosis in Immune-mediated Diseases.
PMID- 26417048
TI - Image-guided Percutaneous Drainage for Treatment of Post-Surgical Anastomotic
Leak in Patients with Crohn's Disease.
AB - BACKGROUND AND AIMS: Anastomotic leaks with abscess formation are a common
complication after bowel surgery in Crohn's disease patients. Image-guided
percutaneous drainage is an attractive alternative to reoperation because of
decreased morbidity and length of hospital stay. Because data for this specific
population are scarce, the purpose of this study is to determine the safety and
efficacy of image-guided percutaneous drainage in the management of post-surgical
anastomotic leak in patients with Crohn's disease. METHODS: A total of 41
patients who underwent percutaneous drain placement for the treatment of fluid
collections due to anastomotic leak from September 2004 to November 2013 were
retrospectively identified from the electronic medical record and picture
archiving and communication system. Data recorded included number, size, and
location of anastomotic leaks, number of drains placed, number of follow-up
visits, post-drainage complications, abscess resolution, and subsequent
surgeries. RESULTS: In all, 41 patients with 76 fluid collections were identified
as having received percutaneous drains. The mean number of targeted fluid
collections per patient was 1.5, and the mean duration between surgery and
percutaneous drain placement was 18.5 days. The mean number of drains placed was
1.6, and the median drain size was 10 French [range 8-16 French]. One of 41
[2.4%] patients experienced a minor complication from drain placement [injury to
a superficial abdominal artery] and no major complications occurred. Two of 41
[4.9%] patients required repeat surgeries. CONCLUSIONS: Image-guided percutaneous
drainage for the treatment of post-surgical anastomotic leaks in Crohn's patients
is effective and safe, with low rates of complications and reoperations.
PMID- 26417050
TI - Vigilante Science.
PMID- 26417049
TI - Autophagy Contributes to the Induction of Anti-TNF Induced Macrophages.
AB - BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] antibodies induce
regulatory macrophages which display a phenotype resembling M2 type macrophages.
Anti-TNF induced macrophages [Mphiind] have immunosuppressive and wound healing
properties. The factors that contribute to the induction of Mphiind remain to be
explored. Autophagy has been described as a factor that is important for the
induction and function of M2 type macrophages. We studied the contribution of
autophagy to the induction of Mphiind. METHODS: We studied the effect of
autophagy on Mphiind in vitro using peripheral blood mononuclear cells.
Interferon gamma [IFN-gamma] induced macrophages [Mphi1] were generated by
culturing monocytes in the presence of IFN-gamma. Mphiind were generated by
performing mixed lymphocyte reactions [MLR] in the presence of anti-TNF
antibodies; 28 healthy donors were genotyped for rs_2241880 [ATG16L1]. Cells were
analysed by autophagy gene array, immunofluorescence, western blot,
flowcytometry, 3H-thymidine incorporation and MTS assay. RESULTS: Mphiind had a
different expression profile of autophagy related transcripts with increased
expression of 33/40 altered genes compared with Mphi1. In addition, autophagic
activity was increased in Mphiind compared with Mphi1. Induction of Mphiind was
positively correlated to the number of wild-type alleles for the ATG16L1 T300A
risk allele present in the culture. Finally, the autophagy-related protein
cathepsin S was highly expressed in Mphiind and inhibition resulted in decreased
viability as well as decreased expression of CD206. CONCLUSIONS: Mphiind have
increased levels of autophagy compared with inflammatory Mphi1, and the induction
of these macrophages is impaired in donors carrying the T300A risk allele for the
ATG16L1. Given the association between Mphiind and clinical response, this
suggests that an intact autophagy pathway may be important for an optimal
response to anti-TNF therapy in inflammatory bowel disease.
PMID- 26417051
TI - Visualizing the Photosynthetic Membrane Proteins in Situ: Atomic Force
Microscopy.
PMID- 26417052
TI - Nutrient Signaling by Nitrate and Calcium.
PMID- 26417053
TI - From Leaf to Kernel: Trehalose-6-Phosphate Signaling Moves Carbon in the Field.
PMID- 26417054
TI - CORRECTIONS.
PMID- 26417055
TI - CORRECTIONS.
PMID- 26417056
TI - Corrigendum.
AB - Treatment steps, surgery and hospitalization rates during the first year of
follow-up in patients with inflammatory bowel diseases from the 2011 ECCO-EpiCom
inception cohort. This paper, which was previously published in Vol. 9 Iss. 9,
listed an incorrect author name. Limas Kupcinskas was incorrectly referred to as
'Limas Kupcinskap'.
PMID- 26417058
TI - Beyond ejection fraction: an integrative approach for assessment of cardiac
structure and function in heart failure.
AB - Left ventricular ejection fraction (LVEF) has been the central parameter used for
diagnosis and management in patients with heart failure. A good predictor of
adverse outcomes in heart failure when below ~45%, LVEF is less useful as a
marker of risk as it approaches normal. As a measure of cardiac function,
ejection fraction has several important limitations. Calculated as the stroke
volume divided by end-diastolic volume, the estimation of ejection fraction is
generally based on geometric assumptions that allow for assessment of volumes
based on linear or two-dimensional measurements. Left ventricular ejection
fraction is both preload- and afterload-dependent, can change substantially based
on loading conditions, is only moderately reproducible, and represents only a
single measure of risk in patients with heart failure. Moreover, the relationship
between ejection fraction and risk in patients with heart failure is modified by
factors such as hypertension, diabetes, and renal function. A more complete
evaluation and understanding of left ventricular function in patients with heart
failure requires a more comprehensive assessment: we conceptualize an integrative
approach that incorporates measures of left and right ventricular function, left
ventricular geometry, left atrial size, and valvular function, as well as non
imaging factors (such as clinical parameters and biomarkers), providing a
comprehensive and accurate prediction of risk in heart failure.
PMID- 26417057
TI - Growth differentiation factor-15 level predicts major bleeding and cardiovascular
events in patients with acute coronary syndromes: results from the PLATO study.
AB - AIMS: Growth differentiation factor-15 (GDF-15) predicts death and composite
cardiovascular (CV) events in patients with acute coronary syndrome (ACS). We
investigated the independent associations between GDF-15 levels and major
bleeding, the extent of coronary lesions and individual CV events in patients
with ACS. METHODS AND RESULTS: Growth differentiation factor-15 was analysed at
baseline ( ITALIC! n = 16 876) in patients with ACS randomized to ticagrelor or
clopidogrel in the PLATO (PLATelet inhibition and patient Outcomes) trial. Growth
differentiation factor-15 levels were related to extent of coronary artery
disease (CAD) and to all types of non-coronary artery bypass grafting (CABG)
related major bleeding, spontaneous myocardial infarction (MI), stroke, and death
during 12-month follow-up. In Cox proportional hazards models adjusting for
established risk factors for CV disease and prognostic biomarkers (N-terminal pro
B-type natriuretic peptide, cystatin C, high-sensitive C-reactive protein, and
high-sensitive troponin T), 1 SD increase in ln GDF-15 was associated with
increased risk of major bleeding with a hazard ratio (HR) 1.37 (95% confidence
interval: 1.25-1.51) and with a similar increase in risk across different
bleeding locations. For the same increase in ln GDF-15, the HR for the composite
of CV death, spontaneous MI, and stroke was 1.29 (1.21-1.37), CV death 1.41 (1.30
1.53), all-cause death 1.41 (1.31-1.53), spontaneous MI 1.15 (1.05-1.26), and
stroke 1.19 (1.01-1.42). The ITALIC! C-statistic improved for the prediction of
CV death and non-CABG-related major bleeding when adding GDF-15 to established
risk factors. CONCLUSIONS: In patients with ACS, higher levels of GDF-15 are
associated with raised risks of all types of major non-CABG-related bleeding,
spontaneous MI, and stroke as well as CV and total mortality and seem to improve
risk stratification for CV-mortality and major bleeding beyond established risk
factors. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov; NCT00391872.
PMID- 26417059
TI - Sonolysis in Prevention of Brain Infarction During Carotid Endarterectomy and
Stenting (SONOBUSTER): a randomized, controlled trial.
AB - AIMS: Previous case series have detected silent brain infarctions in as many as
one-third of patients after carotid endarterectomy (CEA) and in up to two-thirds
of patients after carotid angioplasty and stenting (CAS). Sonolysis employs
ultrasound to facilitate disruption of thrombi and has been shown to be safe and
effective for improving long-term outcomes following acute stroke. Here, we
examined whether intraoperative sonolysis alters the risk of new brain ischaemic
lesions during CEA or CAS. METHODS AND RESULTS: All consecutive patients with
internal carotid stenosis >=70% indicated for CEA/CAS were screened in this
prospective study. Patients were allocated randomly to sonolysis and control
groups. Neurological examination, cognitive function tests, and brain magnetic
resonance imaging (MRI) were conducted before intervention and at 24 and 30 days
post-surgery. Of the 487 screened patients, 121 (87 males; mean age, 66.65 +/-
7.17 years) were allocated to the sonolysis group and 121 (75; 66.02 +/- 8.11
years) to the control group. New brain ischaemic lesions on post-procedure MRI
were significantly less frequent in the sonolysis group than in the control group
(31.4% of patients vs. 47.1%; P = 0.018). Sonolysis and CEA were identified as
independent predictors of reduced brain ischaemic risk [sonolysis: odds ratio
(OR) = 0.450 (0.215-0.942), P = 0.034 and CEA: OR = 0.208 (0.087-0.495), P <
0.001]. Stroke or transient ischaemic attack occurred in one sonolysis patient
and three control patients (P = 0.372). No significant group differences were
found in post-intervention cognitive test scores (P > 0.3). CONCLUSION: This
study provides Class II evidence that sonolysis during CEA or CAS reduces the
risk of new brain ischaemic lesions. CLINICAL TRIAL REGISTRATION:
http://www.clinicaltrials.gov (NCT01591005).
PMID- 26417062
TI - Single-incision thoracoscopic surgery and conventional video-assisted
thoracoscopic surgery: a retrospective comparative study of perioperative
clinical outcomes?.
AB - OBJECTIVES: To assess the feasibility, safety and postoperative wound pain of
single-incision thoracoscopic surgery (SITS) for Stage I lung cancer in patients
who had previously undergone surgery compared with conventional video-assisted
thoracoscopic surgery (c-VATS). METHODS: Lobectomy by SITS (60) and c-VATS (20)
was performed for Stage I lung cancer between 2011 and 2014. In SITS, an ~ 5-cm
small incision was placed at the fourth or fifth intercostal space from the
anterior to posterior axillary line. C-VATS was performed via three or four ports
using trocars only. The evaluation items were general operative outcomes, pain
stress using the Numeric Rating scale (NRS) on postoperative days 3, 7 and 30,
and some pathological symptoms related to the neuropathic wound pain through the
operative course. The number of days of use of analgesic agents was also
evaluated for 1 month after surgery. RESULTS: SITS showed similar perioperative
outcomes (postoperative hospital stay, blood loss, surgical time, drainage
duration, creatine phosphokinase (CPKmax), creactive protein (CRPmax) and
frequency of postoperative complications) to those of c-VATS. Additionally, the
average NRS in SITS decreased on postoperative days 7 and 30 (Day 7: 2.4 +/- 0.4
vs 4.2 +/- 0.3, P = 0.041, Day 30: 1.7 +/- 0.4 vs 3.3 +/- 0.3, P = 0.038) and the
number of days analgesic agents were administered was also reduced (SITS: 8.1 +/-
0.9 vs c-VATS 13.1 +/- 1.2 days, P = 0.045). The frequency of allodynia,
hyperalgesia, hypaesthesia and numbness was significantly reduced in the SITS
group. CONCLUSIONS: Although conclusive evidence has not yet been obtained, SITS
is more minimally invasive in regard to postoperative wound pain compared with c
VATS. This procedure should be considered as a treatment option for early-stage
lung cancer.
PMID- 26417063
TI - Reply to Kadan et al.
PMID- 26417061
TI - Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for
Atrial Fibrillation (EAST-AF) trial.
AB - AIMS: Substantial portion of early arrhythmia recurrence after catheter ablation
for atrial fibrillation (AF) is considered to be due to irritability in left
atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use
of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of
early arrhythmia recurrence and thereby promote reverse remodelling of LA,
leading to improved long-term clinical outcomes. METHODS AND RESULTS: A total of
2038 patients who had undergone radiofrequency catheter ablation for paroxysmal,
persistent, or long-lasting AF were randomly assigned to either 90-day use of
Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients)
group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30
s or those requiring repeat ablation, hospital admission, or usage of class I or
III AAD at 1 year, following the treatment period of 90 days post ablation.
Patients assigned to AAD were associated with significantly higher event-free
rate from recurrent atrial tachyarrhythmias when compared with the control group
during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted
hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01].
However, there was no significant difference in the 1-year event-free rates from
the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted
HR 0.93; 95% CI 0.79-1.09; P = 0.38). CONCLUSION: Short-term use of AAD for 90
days following AF ablation reduced the incidence of recurrent atrial
tachyarrhythmias during the treatment period, but it did not lead to improved
clinical outcomes at the later phase.
PMID- 26417060
TI - Stent thrombosis and restenosis: what have we learned and where are we going? The
Andreas Gruntzig Lecture ESC 2014.
AB - Modern-day stenting procedures leverage advances in pharmacotherapy and device
innovation. Patients treated with contemporary antiplatelet agents, peri
procedural antithrombin therapy and new-generation drug-eluting stents (DES) have
excellent outcomes over the short to medium term. Indeed, coupled with the
reducing costs of these devices in most countries there remain very few
indications where patients should be denied treatment with standard-of-care DES
therapy. The two major causes of stent failure are stent thrombosis (ST) and in
stent restenosis (ISR). The incidence of both has reduced considerably in recent
years. Current clinical registries and randomized trials with broad inclusion
criteria show rates of ST at or <1% after 1 year and ~0.2-0.4% per year
thereafter; rates of clinical ISR are 5% respectively. Angiographic surveillance
studies in large cohorts show rates of angiographic ISR of ~10% with new
generation DES. The advent of high-resolution intracoronary imaging has shown
that in many cases of late stent failure neoatherosclerotic change within the
stented segment represents a final common pathway for both thrombotic and
restenotic events. In future, a better understanding of the pathogenesis of this
process may translate into improved late outcomes. Moreover, the predominance of
non-stent-related disease as a cause of subsequent myocardial infarction during
follow-up highlights the importance of lifestyle and pharmacological
interventions targeted at modification of the underlying disease process.
Finally, although recent developments focus on strategies which circumvent the
need for chronically indwelling stents--such as drug-coated balloons or fully
bioresorbable stents-more data are needed before the wider use of these therapies
can be advocated.
PMID- 26417064
TI - Red cell distribution width may not have a good prospective predictive value in
patients with transcatheter aortic valve implantation.
PMID- 26417065
TI - DIAGNOSIS OF ENDOCRINE DISEASE: On the need for national-, racial-, or ethnic
specific standards for the assessment of bone maturation.
AB - In an attempt to overcome ethnic and racial differences in skeletal maturation,
the use of ethnic-specific standards has been suggested. Do we need such
standards? Based on a fundamental understanding of phenotypic plasticity and an
individual's ability to respond to environmental cues, the author argues that we
do not need ethnic-specific standards for bone maturity. I suggest that we use a
unified international standard of bone maturity for comparing the health,
nutrition, and quality of life of all children, regardless of their race,
nationality, and ethnicity.
PMID- 26417066
TI - The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to
regulate cervical cancer progression.
AB - The Hippo signaling pathway controls organ size and tumorigenesis through a
kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that
YAP plays a central role in controlling the progression of cervical cancer. Our
results suggest that YAP expression is associated with a poor prognosis for
cervical cancer. TGF-alpha and amphiregulin (AREG), via EGFR, inhibit the Hippo
signaling pathway and activate YAP to induce cervical cancer cell proliferation
and migration. Activated YAP allows for up-regulation of TGF-alpha, AREG, and
EGFR, forming a positive signaling loop to drive cervical cancer cell
proliferation. HPV E6 protein, a major etiological molecule of cervical cancer,
maintains high YAP protein levels in cervical cancer cells by preventing
proteasome-dependent YAP degradation to drive cervical cancer cell proliferation.
Results from human cervical cancer genomic databases and an accepted transgenic
mouse model strongly support the clinical relevance of the discovered feed
forward signaling loop. Our study indicates that combined targeting of the Hippo
and the ERBB signaling pathways represents a novel therapeutic strategy for
prevention and treatment of cervical cancer.
PMID- 26417068
TI - Endothelial miR-17~92 cluster negatively regulates arteriogenesis via miRNA-19
repression of WNT signaling.
AB - The contribution of endothelial-derived miR-17~92 to ischemia-induced
arteriogenesis has not been investigated in an in vivo model. In the present
study, we demonstrate a critical role for the endothelial-derived miR-17~92
cluster in shaping physiological and ischemia-triggered arteriogenesis.
Endothelial-specific deletion of miR-17~92 results in an increase in collateral
density limbs and hearts and in ischemic limbs compared with control mice, and
consequently improves blood flow recovery. Individual cluster components
positively or negatively regulate endothelial cell (EC) functions in vitro, and,
remarkably, ECs lacking the cluster spontaneously form cords in a manner rescued
by miR-17a, -18a, and -19a. Using both in vitro and in vivo analyses, we
identified FZD4 and LRP6 as targets of miR-19a/b. Both of these targets were up
regulated in 17~92 KO ECs compared with control ECs, and both were shown to be
targeted by miR-19 using luciferase assays. We demonstrate that miR-19a
negatively regulates FZD4, its coreceptor LRP6, and WNT signaling, and that
antagonism of miR-19a/b in aged mice improves blood flow recovery after ischemia
and reduces repression of these targets. Collectively, these data provide
insights into miRNA regulation of arterialization and highlight the importance of
vascular WNT signaling in maintaining arterial blood flow.
PMID- 26417067
TI - Defective autophagy is a key feature of cerebral cavernous malformations.
AB - Cerebral cavernous malformation (CCM) is a major cerebrovascular disease
affecting approximately 0.3-0.5% of the population and is characterized by
enlarged and leaky capillaries that predispose to seizures, focal neurological
deficits, and fatal intracerebral hemorrhages. Cerebral cavernous malformation is
a genetic disease that may arise sporadically or be inherited as an autosomal
dominant condition with incomplete penetrance and variable expressivity.
Causative loss-of-function mutations have been identified in three genes, KRIT1
(CCM1), CCM2 (MGC4607), and PDCD10 (CCM3), which occur in both sporadic and
familial forms. Autophagy is a bulk degradation process that maintains
intracellular homeostasis and that plays essential quality control functions
within the cell. Indeed, several studies have identified the association between
dysregulated autophagy and different human diseases. Here, we show that the
ablation of the KRIT1 gene strongly suppresses autophagy, leading to the aberrant
accumulation of the autophagy adaptor p62/SQSTM1, defective quality control
systems, and increased intracellular stress. KRIT1 loss-of-function activates the
mTOR-ULK1 pathway, which is a master regulator of autophagy, and treatment with
mTOR inhibitors rescues some of the mole-cular and cellular phenotypes associated
with CCM. Insufficient autophagy is also evident in CCM2-silenced human
endothelial cells and in both cells and tissues from an endothelial-specific CCM3
knockout mouse model, as well as in human CCM lesions. Furthermore, defective
autophagy is highly correlated to endothelial-to-mesenchymal transition, a
crucial event that contributes to CCM progression. Taken together, our data point
to a key role for defective autophagy in CCM disease pathogenesis, thus providing
a novel framework for the development of new pharmacological strategies to
prevent or reverse adverse clinical outcomes of CCM lesions.
PMID- 26417070
TI - Glacial reduction and millennial-scale variations in Drake Passage throughflow.
AB - The Drake Passage (DP) is the major geographic constriction for the Antarctic
Circumpolar Current (ACC) and exerts a strong control on the exchange of
physical, chemical, and biological properties between the Atlantic, Pacific, and
Indian Ocean basins. Resolving changes in the flow of circumpolar water masses
through this gateway is, therefore, crucial for advancing our understanding of
the Southern Ocean's role in global ocean and climate variability. Here, we
reconstruct changes in DP throughflow dynamics over the past 65,000 y based on
grain size and geochemical properties of sediment records from the southernmost
continental margin of South America. Combined with published sediment records
from the Scotia Sea, we argue for a considerable total reduction of DP transport
and reveal an up to ~ 40% decrease in flow speed along the northernmost ACC
pathway entering the DP during glacial times. Superimposed on this long-term
decrease are high-amplitude, millennial-scale variations, which parallel Southern
Ocean and Antarctic temperature patterns. The glacial intervals of strong
weakening of the ACC entering the DP imply an enhanced export of northern ACC
surface and intermediate waters into the South Pacific Gyre and reduced Pacific
Atlantic exchange through the DP ("cold water route"). We conclude that changes
in DP throughflow play a critical role for the global meridional overturning
circulation and interbasin exchange in the Southern Ocean, most likely regulated
by variations in the westerly wind field and changes in Antarctic sea ice extent.
PMID- 26417069
TI - A new therapeutic effect of simvastatin revealed by functional improvement in
muscular dystrophy.
AB - Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with
no effective treatment. DMD muscle pathogenesis is characterized by chronic
inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering
drugs, inhibit these deleterious processes in ischemic diseases affecting
skeletal muscle, and therefore have potential to improve DMD. However, statins
have not been considered for DMD, or other muscular dystrophies, principally
because skeletal-muscle-related symptoms are rare, but widely publicized, side
effects of these drugs. Here we show positive effects of statins in dystrophic
skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle
function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly
improved overall muscle health in mdx mice, reducing plasma creatine kinase
activity, an established measure of muscle damage, to near-normal levels. This
reduction was accompanied by reduced inflammation, more oxidative muscle fibers,
and improved strength of the weak diaphragm muscle. Shorter-term treatment
protected against muscle fatigue and increased mdx hindlimb muscle force by 40%,
a value comparable to current dystrophin gene-based therapies. Increased force
correlated with reduced NADPH Oxidase 2 protein expression, the major source of
oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe
muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a
major cause of functional decline in DMD. These improvements were accompanied by
autophagy activation, a recent therapeutic target for DMD, and less oxidative
stress. Together, our findings highlight that simvastatin substantially improves
the overall health and function of dystrophic skeletal muscles and may provide an
unexpected, novel therapy for DMD and related neuromuscular diseases.
PMID- 26417071
TI - Mechanisms of cyclic AMP/protein kinase A- and glucocorticoid-mediated apoptosis
using S49 lymphoma cells as a model system.
AB - Cyclic AMP/protein kinase A (cAMP/PKA) and glucocorticoids promote the death of
many cell types, including cells of hematopoietic origin. In wild-type (WT) S49 T
lymphoma cells, signaling by cAMP and glucocorticoids converges on the induction
of the proapoptotic B-cell lymphoma-family protein Bim to produce mitochondria
dependent apoptosis. Kin(-), a clonal variant of WT S49 cells, lacks PKA
catalytic (PKA-Calpha) activity and is resistant to cAMP-mediated apoptosis.
Using sorbitol density gradient fractionation, we show here that in kin(-) S49
cells PKA-Calpha is not only depleted but the residual PKA-Calpha mislocalizes to
heavier cell fractions and is not phosphorylated at two conserved residues
(Ser(338) or Thr(197)). In WT S49 cells, PKA-regulatory subunit I (RI) and Bim
coimmunoprecipitate upon treatment with cAMP analogs and forskolin (which
increases endogenous cAMP concentrations). By contrast, in kin(-) cells,
expression of PKA-RIalpha and Bim is prominently decreased, and increases in cAMP
do not increase Bim expression. Even so, kin(-) cells undergo apoptosis in
response to treatment with the glucocorticoid dexamethasone (Dex). In WT cells,
glucorticoid-mediated apoptosis involves an increase in Bim, but in kin(-) cells,
Dex-promoted cell death appears to occur by a caspase 3-independent apoptosis
inducing factor pathway. Thus, although cAMP/PKA-Calpha and PKA-R1alpha/Bim
mediate apoptotic cell death in WT S49 cells, kin(-) cells resist this response
because of lower levels of PKA-Calpha and PKA-RIalpha subunits as well as Bim.
The findings for Dex-promoted apoptosis imply that these lymphoma cells have
adapted to selective pressure that promotes cell death by altering canonical
signaling pathways.
PMID- 26417072
TI - Mechanisms of leiomodin 2-mediated regulation of actin filament in muscle cells.
AB - Leiomodin (Lmod) is a class of potent tandem-G-actin-binding nucleators in muscle
cells. Lmod mutations, deletion, or instability are linked to lethal nemaline
myopathy. However, the lack of high-resolution structures of Lmod nucleators in
action severely hampered our understanding of their essential cellular functions.
Here we report the crystal structure of the actin-Lmod2162-495 nucleus. The
structure contains two actin subunits connected by one Lmod2162-495 molecule in a
non-filament-like conformation. Complementary functional studies suggest that the
binding of Lmod2 stimulates ATP hydrolysis and accelerates actin nucleation and
polymerization. The high level of conservation among Lmod proteins in sequence
and functions suggests that the mechanistic insights of human Lmod2 uncovered
here may aid in a molecular understanding of other Lmod proteins. Furthermore,
our structural and mechanistic studies unraveled a previously unrecognized level
of regulation in mammalian signal transduction mediated by certain tandem-G-actin
binding nucleators.
PMID- 26417073
TI - Contractility of single cardiomyocytes differentiated from pluripotent stem cells
depends on physiological shape and substrate stiffness.
AB - Single cardiomyocytes contain myofibrils that harbor the sarcomere-based
contractile machinery of the myocardium. Cardiomyocytes differentiated from human
pluripotent stem cells (hPSC-CMs) have potential as an in vitro model of heart
activity. However, their fetal-like misalignment of myofibrils limits their
usefulness for modeling contractile activity. We analyzed the effects of cell
shape and substrate stiffness on the shortening and movement of labeled
sarcomeres and the translation of sarcomere activity to mechanical output
(contractility) in live engineered hPSC-CMs. Single hPSC-CMs were cultured on
polyacrylamide substrates of physiological stiffness (10 kPa), and Matrigel
micropatterns were used to generate physiological shapes (2,000-um(2) rectangles
with length:width aspect ratios of 5:1-7:1) and a mature alignment of myofibrils.
Translation of sarcomere shortening to mechanical output was highest in 7:1 hPSC
CMs. Increased substrate stiffness and applied overstretch induced myofibril
defects in 7:1 hPSC-CMs and decreased mechanical output. Inhibitors of nonmuscle
myosin activity repressed the assembly of myofibrils, showing that subcellular
tension drives the improved contractile activity in these engineered hPSC-CMs.
Other factors associated with improved contractility were axially directed
calcium flow, systematic mitochondrial distribution, more mature
electrophysiology, and evidence of transverse-tubule formation. These findings
support the potential of these engineered hPSC-CMs as powerful models for
studying myocardial contractility at the cellular level.
PMID- 26417074
TI - Ecosystem carbon stocks and sequestration potential of federal lands across the
conterminous United States.
AB - Federal lands across the conterminous United States (CONUS) account for 23.5% of
the CONUS terrestrial area but have received no systematic studies on their
ecosystem carbon (C) dynamics and contribution to the national C budgets. The
methodology for US Congress-mandated national biological C sequestration
potential assessment was used to evaluate ecosystem C dynamics in CONUS federal
lands at present and in the future under three Intergovernmental Panel on Climate
Change Special Report on Emission Scenarios (IPCC SRES) A1B, A2, and B1. The
total ecosystem C stock was estimated as 11,613 Tg C in 2005 and projected to be
13,965 Tg C in 2050, an average increase of 19.4% from the baseline. The
projected annual C sequestration rate (in kilograms of carbon per hectare per
year) from 2006 to 2050 would be sinks of 620 and 228 for forests and grasslands,
respectively, and C sources of 13 for shrublands. The federal lands' contribution
to the national ecosystem C budget could decrease from 23.3% in 2005 to 20.8% in
2050. The C sequestration potential in the future depends not only on the
footprint of individual ecosystems but also on each federal agency's land use and
management. The results presented here update our current knowledge about the
baseline ecosystem C stock and sequestration potential of federal lands, which
would be useful for federal agencies to decide management practices to achieve
the national greenhouse gas (GHG) mitigation goal.
PMID- 26417075
TI - Topology-defined units in numerosity perception.
AB - What is a number? The number sense hypothesis suggests that numerosity is "a
primary visual property" like color, contrast, or orientation. However, exactly
what attribute of a stimulus is the primary visual property and determines
numbers in the number sense? To verify the invariant nature of numerosity
perception, we manipulated the numbers of items connected/enclosed in arbitrary
and irregular forms while controlling for low-level features (e.g., orientation,
color, and size). Subjects performed discrimination, estimation, and equality
judgment tasks in a wide range of presentation durations and across small and
large numbers. Results consistently show that connecting/enclosing items led to
robust numerosity underestimation, with the extent of underestimation increasing
monotonically with the number of connected/enclosed items. In contrast, grouping
based on color similarity had no effect on numerosity judgment. We propose that
numbers or the primitive units counted in numerosity perception are influenced by
topological invariants, such as connectivity and the inside/outside relationship.
Beyond the behavioral measures, neural tuning curves to numerosity in the
intraparietal sulcus were obtained using functional MRI adaptation, and the
tuning curves showed that numbers represented in the intraparietal sulcus were
strongly influenced by topology.
PMID- 26417076
TI - Asymmetric nanotopography biases cytoskeletal dynamics and promotes
unidirectional cell guidance.
AB - Many biological and physiological processes depend upon directed migration of
cells, which is typically mediated by chemical or physical gradients or by signal
relay. Here we show that cells can be guided in a single preferred direction
based solely on local asymmetries in nano/microtopography on subcellular scales.
These asymmetries can be repeated, and thereby provide directional guidance, over
arbitrarily large areas. The direction and strength of the guidance is sensitive
to the details of the nano/microtopography, suggesting that this phenomenon plays
a context-dependent role in vivo. We demonstrate that appropriate asymmetric
nano/microtopography can unidirectionally bias internal actin polymerization
waves and that cells move with the same preferred direction as these waves. This
phenomenon is observed both for the pseudopod-dominated migration of the amoeboid
Dictyostelium discoideum and for the lamellipod-driven migration of human
neutrophils. The conservation of this mechanism across cell types and the
asymmetric shape of many natural scaffolds suggest that actin-wave-based guidance
is important in biology and physiology.
PMID- 26417077
TI - Mathematical framework for activity-based cancer biomarkers.
AB - Advances in nanomedicine are providing sophisticated functions to precisely
control the behavior of nanoscale drugs and diagnostics. Strategies that coopt
protease activity as molecular triggers are increasingly important in
nanoparticle design, yet the pharmacokinetics of these systems are challenging to
understand without a quantitative framework to reveal nonintuitive associations.
We describe a multicompartment mathematical model to predict strategies for
ultrasensitive detection of cancer using synthetic biomarkers, a class of
activity-based probes that amplify cancer-derived signals into urine as a
noninvasive diagnostic. Using a model formulation made of a PEG core conjugated
with protease-cleavable peptides, we explore a vast design space and identify
guidelines for increasing sensitivity that depend on critical parameters such as
enzyme kinetics, dosage, and probe stability. According to this model, synthetic
biomarkers that circulate in stealth but then activate at sites of disease have
the theoretical capacity to discriminate tumors as small as 5 mm in diameter-a
threshold sensitivity that is otherwise challenging for medical imaging and blood
biomarkers to achieve. This model may be adapted to describe the behavior of
additional activity-based approaches to allow cross-platform comparisons, and to
predict allometric scaling across species.
PMID- 26417078
TI - Modeling the effect of locus coeruleus firing on cortical state dynamics and
single-trial sensory processing.
AB - Neuronal responses to sensory stimuli are not only driven by feedforward sensory
pathways but also depend upon intrinsic factors (collectively known as the
network state) that include ongoing spontaneous activity and neuromodulation. To
understand how these factors together regulate cortical dynamics, we recorded
simultaneously spontaneous and somatosensory-evoked multiunit activity from
primary somatosensory cortex and from the locus coeruleus (LC) (the
neuromodulatory nucleus releasing norepinephrine) in urethane-anesthetized rats.
We found that bursts of ipsilateral-LC firing preceded by few tens of
milliseconds increases of cortical excitability, and that the 1- to 10-Hz
rhythmicity of LC discharge appeared to increase the power of delta-band (1-4 Hz)
cortical synchronization. To investigate quantitatively how LC firing might
causally influence spontaneous and stimulus-driven cortical dynamics, we then
constructed and fitted to these data a model describing the dynamical interaction
of stimulus drive, ongoing synchronized cortical activity, and noradrenergic
neuromodulation. The model proposes a coupling between LC and cortex that can
amplify delta-range cortical fluctuations, and shows how suitably timed phasic LC
bursts can lead to enhanced cortical responses to weaker stimuli and increased
temporal precision of cortical stimulus-evoked responses. Thus, the temporal
structure of noradrenergic modulation may selectively and dynamically enhance or
attenuate cortical responses to stimuli. Finally, using the model prediction of
single-trial cortical stimulus-evoked responses to discount single-trial state
dependent variability increased by ~70% the sensory information extracted from
cortical responses. This suggests that downstream circuits may extract
information more effectively after estimating the state of the circuit
transmitting the sensory message.
PMID- 26417079
TI - Mesoscopic quantum emitters from deterministic aggregates of conjugated polymers.
AB - An appealing definition of the term "molecule" arises from consideration of the
nature of fluorescence, with discrete molecular entities emitting a stream of
single photons. We address the question of how large a molecular object may
become by growing deterministic aggregates from single conjugated polymer chains.
Even particles containing dozens of individual chains still behave as single
quantum emitters due to efficient excitation energy transfer, whereas the
brightness is raised due to the increased absorption cross-section of the
suprastructure. Excitation energy can delocalize between individual polymer
chromophores in these aggregates by both coherent and incoherent coupling, which
are differentiated by their distinct spectroscopic fingerprints. Coherent
coupling is identified by a 10-fold increase in excited-state lifetime and a
corresponding spectral red shift. Exciton quenching due to incoherent FRET
becomes more significant as aggregate size increases, resulting in single
aggregate emission characterized by strong blinking. This mesoscale approach
allows us to identify intermolecular interactions which do not exist in isolated
chains and are inaccessible in bulk films where they are present but masked by
disorder.
PMID- 26417080
TI - Orbital pacing of carbon fluxes by a ~9-My eccentricity cycle during the
Mesozoic.
AB - Eccentricity, obliquity, and precession are cyclic parameters of the Earth's
orbit whose climatic implications have been widely demonstrated on recent and
short time intervals. Amplitude modulations of these parameters on million-year
time scales induce "grand orbital cycles," but the behavior and the
paleoenvironmental consequences of these cycles remain debated for the Mesozoic
owing to the chaotic diffusion of the solar system in the past. Here, we test for
these cycles from the Jurassic to the Early Cretaceous by analyzing new stable
isotope datasets reflecting fluctuations in the carbon cycle and seawater
temperatures. Our results document a prominent cyclicity of ~9 My in the carbon
cycle paced by changes in the seasonal dynamics of hydrological processes and
long-term sea level fluctuations. These paleoenvironmental changes are linked to
a great eccentricity cycle consistent with astronomical solutions. The orbital
forcing signal was mainly amplified by cumulative sequestration of organic matter
in the boreal wetlands under greenhouse conditions. Finally, we show that the ~9
My cycle faded during the Pliensbachian, which could either reflect major
paleoenvironmental disturbances or a chaotic transition affecting this cycle.
PMID- 26417081
TI - Glycan modulation and sulfoengineering of anti-HIV-1 monoclonal antibody PG9 in
plants.
AB - Broadly neutralizing anti-HIV-1 monoclonal antibodies, such as PG9, and its
derivative RSH hold great promise in AIDS therapy and prevention. An important
feature related to the exceptional efficacy of PG9 and RSH is the presence of
sulfated tyrosine residues in their antigen-binding regions. To maximize antibody
functionalities, we have now produced glycan-optimized, fucose-free versions of
PG9 and RSH in Nicotiana benthamiana. Both antibodies were efficiently sulfated
in planta on coexpression of an engineered human tyrosylprotein sulfotransferase,
resulting in antigen-binding and virus neutralization activities equivalent to
PG9 synthesized by mammalian cells ((CHO)PG9). Based on the controlled production
of both sulfated and nonsulfated variants in plants, we could unequivocally prove
that tyrosine sulfation is critical for the potency of PG9 and RSH. Moreover, the
fucose-free antibodies generated in N. benthamiana are capable of inducing
antibody-dependent cellular cytotoxicity, an activity not observed for (CHO)PG9.
Thus, tailoring of the antigen-binding site combined with glycan modulation and
sulfoengineering yielded plant-produced anti-HIV-1 antibodies with effector
functions superior to PG9 made in CHO cells.
PMID- 26417082
TI - Intermittent collective dynamics emerge from conflicting imperatives in sheep
herds.
AB - Among the many fascinating examples of collective behavior exhibited by animal
groups, some species are known to alternate slow group dispersion in space with
rapid aggregation phenomena induced by a sudden behavioral shift at the
individual level. We study this phenomenon quantitatively in large groups of
grazing Merino sheep under controlled experimental conditions. Our analysis
reveals strongly intermittent collective dynamics consisting of fast, avalanche
like regrouping events distributed on all experimentally accessible scales. As a
proof of principle, we introduce an agent-based model with individual behavioral
shifts, which we show to account faithfully for all collective properties
observed. This offers, in turn, an insight on the individual stimulus/response
functions that can generate such intermittent behavior. In particular, the
intensity of sheep allelomimetic behavior plays a key role in the group's ability
to increase the per capita grazing surface while minimizing the time needed to
regroup into a tightly packed configuration. We conclude that the emergent
behavior reported probably arises from the necessity to balance two conflicting
imperatives: (i) the exploration of foraging space by individuals and (ii) the
protection from predators offered by being part of large, cohesive groups. We
discuss our results in the context of the current debate about criticality in
biology.
PMID- 26417084
TI - TMEM16F is required for phosphatidylserine exposure and microparticle release in
activated mouse platelets.
AB - Phosphatidylserine (PtdSer) exposure on the surface of activated platelets
requires the action of a phospholipid scramblase(s), and serves as a scaffold for
the assembly of the tenase and prothrombinase complexes involved in blood
coagulation. Here, we found that the activation of mouse platelets with
thrombin/collagen or Ca(2+) ionophore at 20 degrees C induces PtdSer exposure
without compromising plasma membrane integrity. Among five transmembrane protein
16 (TMEM16) members that support Ca(2+)-dependent phospholipid scrambling,
TMEM16F was the only one that showed high expression in mouse platelets.
Platelets from platelet-specific TMEM16F-deficient mice exhibited defects in
activation-induced PtdSer exposure and microparticle shedding, although alpha
granule and dense granule release remained intact. The rate of tissue factor
induced thrombin generation by TMEM16F-deficient platelets was severely reduced,
whereas thrombin-induced clot retraction was unaffected. The imaging of laser
induced thrombus formation in whole animals showed that PtdSer exposure on
aggregated platelets was TMEM16F-dependent in vivo. The phenotypes of the
platelet-specific TMEM16F-null mice resemble those of patients with Scott
syndrome, a mild bleeding disorder, indicating that these mice may provide a
useful model for human Scott syndrome.
PMID- 26417083
TI - Administration of thimerosal-containing vaccines to infant rhesus macaques does
not result in autism-like behavior or neuropathology.
AB - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some
anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in
the form of the vaccine preservative, thimerosal, and/or receiving the measles,
mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal
containing vaccines (TCVs) following the recommended pediatric vaccine schedules
from the 1990s and 2008, we examined behavior, and neuropathology in three brain
regions found to exhibit neuropathology in postmortem ASD brains. No neuronal
cellular or protein changes in the cerebellum, hippocampus, or amygdala were
observed in animals following the 1990s or 2008 vaccine schedules. Analysis of
social behavior in juvenile animals indicated that there were no significant
differences in negative behaviors between animals in the control and experimental
groups. These data indicate that administration of TCVs and/or the MMR vaccine to
rhesus macaques does not result in neuropathological abnormalities, or aberrant
behaviors, like those observed in ASD.
PMID- 26417086
TI - Genetic specificity of face recognition.
AB - Specific cognitive abilities in diverse domains are typically found to be highly
heritable and substantially correlated with general cognitive ability (g), both
phenotypically and genetically. Recent twin studies have found the ability to
memorize and recognize faces to be an exception, being similarly heritable but
phenotypically substantially uncorrelated both with g and with general object
recognition. However, the genetic relationships between face recognition and
other abilities (the extent to which they share a common genetic etiology) cannot
be determined from phenotypic associations. In this, to our knowledge, first
study of the genetic associations between face recognition and other domains,
2,000 18- and 19-year-old United Kingdom twins completed tests assessing their
face recognition, object recognition, and general cognitive abilities. Results
confirmed the substantial heritability of face recognition (61%), and
multivariate genetic analyses found that most of this genetic influence is unique
and not shared with other cognitive abilities.
PMID- 26417085
TI - Noninvasive brain cancer imaging with a bispecific antibody fragment, generated
via click chemistry.
AB - Early diagnosis remains a task of upmost importance for reducing cancer morbidity
and mortality. Successful development of highly specific companion diagnostics
targeting aberrant molecular pathways of cancer is needed for sensitive
detection, accurate diagnosis, and opportune therapeutic intervention. Herein, we
generated a bispecific immunoconjugate [denoted as Bs-F(ab)2] by linking two
antibody Fab fragments, an anti-epidermal growth factor receptor (EGFR) Fab and
an anti-CD105 Fab, via bioorthogonal "click" ligation of trans-cyclooctene and
tetrazine. PET imaging of mice bearing U87MG (EGFR/CD105(+/+)) tumors with (64)Cu
labeled Bs-F(ab)2 revealed a significantly enhanced tumor uptake [42.9 +/- 9.5
percentage injected dose per gram (%ID/g); n = 4] and tumor-to-background ratio
(tumor/muscle ratio of 120.2 +/- 44.4 at 36 h postinjection; n = 4) compared with
each monospecific Fab tracer. Thus, we demonstrated that dual targeting of EGFR
and CD105 provides a synergistic improvement on both affinity and specificity of
(64)Cu-NOTA-Bs-F(ab)2. (64)Cu-NOTA-Bs-F(ab)2 was able to visualize small U87MG
tumor nodules (<5 mm in diameter), owing to high tumor uptake (31.4 +/- 10.8%ID/g
at 36 h postinjection) and a tumor/muscle ratio of 76.4 +/- 52.3, which provided
excellent sensitivity for early detection. Finally, we successfully confirmed the
feasibility of a ZW800-1-labeled Bs-F(ab)2 for near-infrared fluorescence imaging
and image-guided surgical resection of U87MG tumors. More importantly, our
rationale can be used in the construction of other disease-targeting bispecific
antibody fragments for early detection and diagnosis of small malignant lesions.
PMID- 26417087
TI - NhaA antiporter functions using 10 helices, and an additional 2 contribute to
assembly/stability.
AB - The Escherichia coli Na(+)/H(+) antiporter (Ec-NhaA) is the best-characterized of
all pH-regulated Na(+)/H(+) exchangers that control cellular Na(+) and H(+)
homeostasis. Ec-NhaA has 12 helices, 2 of which (VI and VII) are absent from
other antiporters that share the Ec-NhaA structural fold. This alpha-hairpin is
located in the dimer interface of the Ec-NhaA homodimer together with a beta
sheet. Here we examine computationally and experimentally the role of the alpha
hairpin in the stability, dimerization, transport, and pH regulation of Ec-NhaA.
Evolutionary analysis (ConSurf) indicates that the VI-VII helical hairpin is much
less conserved than the remaining transmembrane region. Moreover, normal mode
analysis also shows that intact NhaA and a variant, deleted of the alpha-hairpin,
share similar dynamics, suggesting that the structure may be dispensable. Thus,
two truncated Ec-NhaA mutants were constructed, one deleted of the alpha-hairpin
and another also lacking the beta-sheet. The mutants were studied at
physiological pH in the membrane and in detergent micelles. The findings
demonstrate that the truncated mutants retain significant activity and regulatory
properties but are defective in the assembly/stability of the Ec-NhaA dimer.
PMID- 26417089
TI - Extent of hippocampal atrophy predicts degree of deficit in recall.
AB - Which specific memory functions are dependent on the hippocampus is still
debated. The availability of a large cohort of patients who had sustained
relatively selective hippocampal damage early in life enabled us to determine
which type of mnemonic deficit showed a correlation with extent of hippocampal
injury. We assessed our patient cohort on a test that provides measures of
recognition and recall that are equated for difficulty and found that the
patients' performance on the recall tests correlated significantly with their
hippocampal volumes, whereas their performance on the equally difficult
recognition tests did not and, indeed, was largely unaffected regardless of
extent of hippocampal atrophy. The results provide new evidence in favor of the
view that the hippocampus is essential for recall but not for recognition.
PMID- 26417088
TI - Adiponectin supplementation in pregnant mice prevents the adverse effects of
maternal obesity on placental function and fetal growth.
AB - Mothers with obesity or gestational diabetes mellitus have low circulating levels
of adiponectin (ADN) and frequently deliver large babies with increased fat mass,
who are susceptible to perinatal complications and to development of metabolic
syndrome later in life. It is currently unknown if the inverse correlation
between maternal ADN and fetal growth reflects a cause-and-effect relationship.
We tested the hypothesis that ADN supplementation in obese pregnant dams improves
maternal insulin sensitivity, restores normal placental insulin/mechanistic
target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and
prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J
mice fed an obesogenic diet before mating and throughout gestation had increased
fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight
ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was
activated, peroxisome proliferator-activated receptor-alpha (PPARalpha)
phosphorylation was reduced, placental transport of glucose and amino acids in
vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN
infusion in obese dams from E14.5 to E18.5 normalized maternal insulin
sensitivity, placental insulin/mTORC1 and PPARalpha signaling, nutrient
transport, and fetal growth without affecting maternal fat mass. Using a mouse
model with striking similarities to obese pregnant women, we demonstrate that ADN
functions as an endocrine link between maternal adipose tissue and fetal growth
by regulating placental function. Importantly, maternal ADN supplementation
reversed the adverse effects of maternal obesity on placental function and fetal
growth. Improving maternal ADN levels may serve as an effective intervention
strategy to prevent fetal overgrowth caused by maternal obesity.
PMID- 26417091
TI - Dark matter universe.
AB - Most of the mass in the universe is in the form of dark matter--a new type of
nonbaryonic particle not yet detected in the laboratory or in other detection
experiments. The evidence for the existence of dark matter through its
gravitational impact is clear in astronomical observations--from the early
observations of the large motions of galaxies in clusters and the motions of
stars and gas in galaxies, to observations of the large-scale structure in the
universe, gravitational lensing, and the cosmic microwave background. The
extensive data consistently show the dominance of dark matter and quantify its
amount and distribution, assuming general relativity is valid. The data inform us
that the dark matter is nonbaryonic, is "cold" (i.e., moves nonrelativistically
in the early universe), and interacts only weakly with matter other than by
gravity. The current Lambda cold dark matter cosmology--a simple (but strange)
flat cold dark matter model dominated by a cosmological constant Lambda, with
only six basic parameters (including the density of matter and of baryons, the
initial mass fluctuations amplitude and its scale dependence, and the age of the
universe and of the first stars)--fits remarkably well all the accumulated data.
However, what is the dark matter? This is one of the most fundamental open
questions in cosmology and particle physics. Its existence requires an extension
of our current understanding of particle physics or otherwise point to a
modification of gravity on cosmological scales. The exploration and ultimate
detection of dark matter are led by experiments for direct and indirect detection
of this yet mysterious particle.
PMID- 26417090
TI - No barrier to emergence of bathyal king crabs on the Antarctic shelf.
AB - Cold-water conditions have excluded durophagous (skeleton-breaking) predators
from the Antarctic seafloor for millions of years. Rapidly warming seas off the
western Antarctic Peninsula could now facilitate their return to the continental
shelf, with profound consequences for the endemic fauna. Among the likely first
arrivals are king crabs (Lithodidae), which were discovered recently on the
adjacent continental slope. During the austral summer of 2010 - 2011, we used
underwater imagery to survey a slope-dwelling population of the lithodid
Paralomis birsteini off Marguerite Bay, western Antarctic Peninsula for
environmental or trophic impediments to shoreward expansion. The population
density averaged ~ 4.5 individuals * 1,000 m(-2) within a depth range of 1,100 -
1,500 m (overall observed depth range 841-2,266 m). Images of juveniles,
discarded molts, and precopulatory behavior, as well as gravid females in a
trapping study, suggested a reproductively viable population on the slope. At the
time of the survey, there was no thermal barrier to prevent the lithodids from
expanding upward and emerging on the outer shelf (400- to 550-m depth); however,
near-surface temperatures remained too cold for them to survive in inner-shelf
and coastal environments (<200 m). Ambient salinity, composition of the
substrate, and the depth distribution of potential predators likewise indicated
no barriers to expansion of lithodids onto the outer shelf. Primary food
resources for lithodids--echinoderms and mollusks--were abundant on the upper
slope (550-800 m) and outer shelf. As sea temperatures continue to rise,
lithodids will likely play an increasingly important role in the trophic
structure of subtidal communities closer to shore.
PMID- 26417092
TI - Placebo analgesia and its opioidergic regulation suggest that empathy for pain is
grounded in self pain.
AB - Empathy for pain activates brain areas partially overlapping with those
underpinning the first-hand experience of pain. It remains unclear, however,
whether such shared activations imply that pain empathy engages similar neural
functions as first-hand pain experiences. To overcome the limitations of previous
neuroimaging research, we pursued a conceptually novel approach: we used the
phenomenon of placebo analgesia to experimentally reduce the first-hand
experience of pain, and assessed whether this results in a concomitant reduction
of empathy for pain. We first carried out a functional MRI experiment (n = 102)
that yielded results in the expected direction: participants experiencing placebo
analgesia also reported decreased empathy for pain, and this was associated with
reduced engagement of anterior insular and midcingulate cortex: that is, areas
previously associated with shared activations in pain and empathy for pain. In a
second step, we used a psychopharmacological manipulation (n = 50) to determine
whether these effects can be blocked via an opioid antagonist. The administration
of the opioid antagonist naltrexone blocked placebo analgesia and also resulted
in a corresponding "normalization" of empathy for pain. Taken together, these
findings suggest that pain empathy may be associated with neural responses and
neurotransmitter activity engaged during first-hand pain, and thus might indeed
be grounded in our own pain experiences.
PMID- 26417093
TI - Motifs of VDAC2 required for mitochondrial Bak import and tBid-induced apoptosis.
AB - Voltage-dependent anion channel (VDAC) proteins are major components of the outer
mitochondrial membrane. VDAC has three isoforms with >70% sequence similarity and
redundant roles in metabolite and ion transport. However, only Vdac2(-/-) (V2(-/
)) mice are embryonic lethal, indicating a unique and fundamental function of
VDAC2 (V2). Recently, a specific V2 requirement was demonstrated for
mitochondrial Bak import and truncated Bid (tBid)-induced apoptosis. To determine
the relevant domain(s) of V2 involved, VDAC1 (V1) and V2 chimeric constructs were
created and used to rescue V2(-/-) fibroblasts. Surprisingly, the commonly cited
V2-specific N-terminal extension and cysteines were found to be dispensable for
Bak import and high tBid sensitivity. In gain-of-function studies, V2 (123-179)
was the minimal sequence sufficient to render V1 competent to support Bak
insertion. Furthermore, in loss-of-function experiments, T168 and D170 were
identified as critical residues. These motifs are conserved in zebrafish V2
(zfV2) that also rescued V2-deficient fibroblasts. Because high-resolution
structures of zfV2 and mammalian V1 have become available, we could superimpose
these structures and recognized that the critical V2-specific residues help to
create a distinctive open "pocket" on the cytoplasmic surface that could
facilitate Bak recruitment.
PMID- 26417094
TI - Chemical, experimental, and morphological evidence for diagenetically altered
melanin in exceptionally preserved fossils.
AB - In living organisms, color patterns, behavior, and ecology are closely linked.
Thus, detection of fossil pigments may permit inferences about important aspects
of ancient animal ecology and evolution. Melanin-bearing melanosomes were
suggested to preserve as organic residues in exceptionally preserved fossils,
retaining distinct morphology that is associated with aspects of original color
patterns. Nevertheless, these oblong and spherical structures have also been
identified as fossilized bacteria. To date, chemical studies have not directly
considered the effects of diagenesis on melanin preservation, and how this may
influence its identification. Here we use time-of-flight secondary ion mass
spectrometry to identify and chemically characterize melanin in a diverse sample
of previously unstudied extant and fossil taxa, including fossils with notably
different diagenetic histories and geologic ages. We document signatures
consistent with melanin preservation in fossils ranging from feathers, to
mammals, to amphibians. Using principal component analyses, we characterize
putative mixtures of eumelanin and phaeomelanin in both fossil and extant
samples. Surprisingly, both extant and fossil amphibians generally exhibit
melanosomes with a mixed eumelanin/phaeomelanin composition rather than pure
eumelanin, as assumed previously. We argue that experimental maturation of modern
melanin samples replicates diagenetic chemical alteration of melanin observed in
fossils. This refutes the hypothesis that such fossil microbodies could be
bacteria, and demonstrates that melanin is widely responsible for the organic
soft tissue outlines in vertebrates found at exceptional fossil localities, thus
allowing for the reconstruction of certain aspects of original pigment patterns.
PMID- 26417095
TI - Enhanced precipitation variability decreases grass- and increases shrub
productivity.
AB - Although projections of precipitation change indicate increases in variability,
most studies of impacts of climate change on ecosystems focused on effects of
changes in amount of precipitation, overlooking precipitation variability
effects, especially at the interannual scale. Here, we present results from a 6-y
field experiment, where we applied sequences of wet and dry years, increasing
interannual precipitation coefficient of variation while maintaining a
precipitation amount constant. Increased precipitation variability significantly
reduced ecosystem primary production. Dominant plant-functional types showed
opposite responses: perennial-grass productivity decreased by 81%, whereas shrub
productivity increased by 67%. This pattern was explained by different nonlinear
responses to precipitation. Grass productivity presented a saturating response to
precipitation where dry years had a larger negative effect than the positive
effects of wet years. In contrast, shrubs showed an increasing response to
precipitation that resulted in an increase in average productivity with
increasing precipitation variability. In addition, the effects of precipitation
variation increased through time. We argue that the differential responses of
grasses and shrubs to precipitation variability and the amplification of this
phenomenon through time result from contrasting root distributions of grasses and
shrubs and competitive interactions among plant types, confirmed by structural
equation analysis. Under drought conditions, grasses reduce their abundance and
their ability to absorb water that then is transferred to deep soil layers that
are exclusively explored by shrubs. Our work addresses an understudied dimension
of climate change that might lead to widespread shrub encroachment reducing the
provisioning of ecosystem services to society.
PMID- 26417097
TI - Vaccines and autism in primate model.
PMID- 26417096
TI - Metabotropic glutamate receptor signaling is required for NMDA receptor-dependent
ocular dominance plasticity and LTD in visual cortex.
AB - A feature of early postnatal neocortical development is a transient peak in
signaling via metabotropic glutamate receptor 5 (mGluR5). In visual cortex, this
change coincides with increased sensitivity of excitatory synapses to monocular
deprivation (MD). However, loss of visual responsiveness after MD occurs via
mechanisms revealed by the study of long-term depression (LTD) of synaptic
transmission, which in layer 4 is induced by acute activation of NMDA receptors
(NMDARs) rather than mGluR5. Here we report that chronic postnatal down
regulation of mGluR5 signaling produces coordinated impairments in both NMDAR
dependent LTD in vitro and ocular dominance plasticity in vivo. The data suggest
that ongoing mGluR5 signaling during a critical period of postnatal development
establishes the biochemical conditions that are permissive for activity-dependent
sculpting of excitatory synapses via the mechanism of NMDAR-dependent LTD.
PMID- 26417099
TI - Naturalization fosters the long-term political integration of immigrants.
AB - Does naturalization cause better political integration of immigrants into the
host society? Despite heated debates about citizenship policy, there exists
almost no evidence that isolates the independent effect of naturalization from
the nonrandom selection into naturalization. We provide new evidence from a
natural experiment in Switzerland, where some municipalities used referendums as
the mechanism to decide naturalization requests. Balance checks suggest that for
close naturalization referendums, which are decided by just a few votes, the
naturalization decision is as good as random, so that narrowly rejected and
narrowly approved immigrant applicants are similar on all confounding
characteristics. This allows us to remove selection effects and obtain unbiased
estimates of the long-term impacts of citizenship. Our study shows that for the
immigrants who faced close referendums, naturalization considerably improved
their political integration, including increases in formal political
participation, political knowledge, and political efficacy.
PMID- 26417098
TI - Global biogeography of human infectious diseases.
AB - The distributions of most infectious agents causing disease in humans are poorly
resolved or unknown. However, poorly known and unknown agents contribute to the
global burden of disease and will underlie many future disease risks. Existing
patterns of infectious disease co-occurrence could thus play a critical role in
resolving or anticipating current and future disease threats. We analyzed the
global occurrence patterns of 187 human infectious diseases across 225 countries
and seven epidemiological classes (human-specific, zoonotic, vector-borne, non
vector-borne, bacterial, viral, and parasitic) to show that human infectious
diseases exhibit distinct spatial grouping patterns at a global scale. We
demonstrate, using outbreaks of Ebola virus as a test case, that this spatial
structuring provides an untapped source of prior information that could be used
to tighten the focus of a range of health-related research and management
activities at early stages or in data-poor settings, including disease
surveillance, outbreak responses, or optimizing pathogen discovery. In examining
the correlates of these spatial patterns, among a range of geographic,
epidemiological, environmental, and social factors, mammalian biodiversity was
the strongest predictor of infectious disease co-occurrence overall and for six
of the seven disease classes examined, giving rise to a striking congruence
between global pathogeographic and "Wallacean" zoogeographic patterns. This clear
biogeographic signal suggests that infectious disease assemblages remain
fundamentally constrained in their distributions by ecological barriers to
dispersal or establishment, despite the homogenizing forces of globalization.
Pathogeography thus provides an overarching context in which other factors
promoting infectious disease emergence and spread are set.
PMID- 26417100
TI - Stress impairs cognitive flexibility in infants.
AB - In human adults, learning and memory under acute stress are characterized by an
increased use of rigid habitual response strategies at the cost of flexible
cognitive strategies. The immediate effects of stress on cognitive functioning
early in life are not well understood. Here we show experimentally that acute
stress leads human infants to perform habitual behavior rigidly. We found that 15
mo-old infants exposed to stress thereafter kept performing a previously
effective action, even after the action suddenly became ineffective. Infants in a
no-stress control group flexibly adjusted their behavior by disengaging from the
newly ineffective action in favor of exploring an alternative action. This
finding demonstrates that stress impairs infants' ability to adjust their
behavior to changing circumstances.
PMID- 26417102
TI - Opinion: The time has come for offshore wind power in the United States.
PMID- 26417101
TI - Generation of Th17 cells in response to intranasal infection requires TGF-beta1
from dendritic cells and IL-6 from CD301b+ dendritic cells.
AB - Intranasal (i.n.) infections preferentially generate Th17 cells. We explored the
basis for this anatomic preference by tracking polyclonal CD4(+) T cells specific
for an MHC class II-bound peptide from the mucosal pathogen Streptococcus
pyogenes. S. pyogenes MHC class II-bound peptide-specific CD4(+) T cells were
first activated in the cervical lymph nodes following i.n. inoculation and then
differentiated into Th17 cells. S. pyogenes-induced Th17 formation depended on
TGF-beta1 from dendritic cells and IL-6 from a CD301b(+) dendritic cell subset
located in the cervical lymph nodes but not the spleen. Thus, the tendency of
i.n. infection to induce Th17 cells is related to cytokine production by
specialized dendritic cells that drain this site.
PMID- 26417103
TI - Evolution of moth sex pheromone composition by a single amino acid substitution
in a fatty acid desaturase.
AB - For sexual communication, moths primarily use blends of fatty acid derivatives
containing one or more double bonds in various positions and configurations,
called sex pheromones (SPs). To study the molecular basis of novel SP component
(SPC) acquisition, we used the tobacco hornworm (Manduca sexta), which uses a
blend of mono-, di-, and uncommon triunsaturated fatty acid (3UFA) derivatives as
SP. We identified pheromone-biosynthetic fatty acid desaturases (FADs) MsexD3,
MsexD5, and MsexD6 abundantly expressed in the M. sexta female pheromone gland.
Their functional characterization and in vivo application of FAD substrates
indicated that MsexD3 and MsexD5 biosynthesize 3UFAs via E/Z14 desaturation from
diunsaturated fatty acids produced by previously characterized Z11
desaturase/conjugase MsexD2. Site-directed mutagenesis of sequentially highly
similar MsexD3 and MsexD2 demonstrated that swapping of a single amino acid in
the fatty acyl substrate binding tunnel introduces E/Z14-desaturase specificity
to mutated MsexD2. Reconstruction of FAD gene phylogeny indicates that MsexD3 was
recruited for biosynthesis of 3UFA SPCs in M. sexta lineage via gene duplication
and neofunctionalization, whereas MsexD5 representing an alternative 3UFA
producing FAD has been acquired via activation of a presumably inactive ancestral
MsexD5. Our results demonstrate that a change as small as a single amino acid
substitution in a FAD enzyme might result in the acquisition of new SP compounds.
PMID- 26417104
TI - New roles for DNA cytosine modification, eRNA, anchors, and superanchors in
developing B cell progenitors.
AB - B-cell fate is orchestrated by a series of well-characterized developmental
regulators. Here, we found that the onset of B-cell development was accompanied
by large-scale changes in DNA cytosine modifications associated with promoters,
enhancers, and anchors. These changes were tightly linked to alterations in
transcription factor occupancy and nascent RNA (eRNA) transcription. We found
that the prepro-B to the pro-B-cell transition was associated with a global
exchange of DNA cytosine modifications for polycomb-mediated repression at CpG
islands. Hypomethylated regions were found exclusively in the active/permissive
compartment of the nucleus and were predominantly associated with regulatory
elements or anchors that orchestrate the folding patterns of the genome. We
identified superanchors, characterized by clusters of hypomethylated CCCTC
binding factor (CTCF)-bound elements, which were predominantly located at
boundaries that define topological associated domains. A particularly prominent
hypomethylated superanchor was positioned down-stream of the Ig heavy chain (Igh)
locus. Analysis of global formaldehyde-cross-linking studies indicated that the
Igh locus superanchor interacts with the VH region repertoire across vast genomic
distances. We propose that the Igh locus superanchor sequesters the VH and DHJH
regions into a spatial confined geometric environment to promote rapid first
passage times. Collectively, these studies demonstrate how, in developing B
cells, DNA cytosine modifications associated with regulatory and architectural
elements affect patterns of gene expression, folding patterns of the genome, and
antigen receptor assembly.
PMID- 26417107
TI - Experimental test of the viscous anisotropy hypothesis for partially molten
rocks.
AB - Chemical differentiation of rocky planets occurs by melt segregation away from
the region of melting. The mechanics of this process, however, are complex and
incompletely understood. In partially molten rocks undergoing shear deformation,
melt pockets between grains align coherently in the stress field; it has been
hypothesized that this anisotropy in microstructure creates an anisotropy in the
viscosity of the aggregate. With the inclusion of anisotropic viscosity,
continuum, two-phase-flow models reproduce the emergence and angle of melt
enriched bands that form in laboratory experiments. In the same theoretical
context, these models also predict sample-scale melt migration due to a gradient
in shear stress. Under torsional deformation, melt is expected to segregate
radially inward. Here we present torsional deformation experiments on partially
molten rocks that test this prediction. Microstructural analyses of the
distribution of melt and solid reveal a radial gradient in melt fraction, with
more melt toward the center of the cylinder. The extent of this radial melt
segregation grows with progressive strain, consistent with theory. The agreement
between theoretical prediction and experimental observation provides a validation
of this theory.
PMID- 26417106
TI - The TWD40-2 protein and the AP2 complex cooperate in the clathrin-mediated
endocytosis of cellulose synthase to regulate cellulose biosynthesis.
AB - Cellulose biosynthesis is performed exclusively by plasma membrane-localized
cellulose synthases (CESAs). Therefore, the trafficking of CESAs to and from the
plasma membrane is an important mechanism for regulating cellulose biosynthesis.
CESAs were recently identified as cargo proteins of the classic adaptor protein 2
(AP2) complex of the clathrin-mediated endocytosis (CME) pathway. The AP2 complex
of the CME pathway is conserved in yeast, animals, and plants, and has been well
characterized in many systems. In contrast, the recently discovered TPLATE
complex (TPC), which is proposed to function as a CME adaptor complex, is only
conserved in plants and a few other eukaryotes. In this study, we discovered that
the TWD40-2 protein, a putative member of the TPC, is also important for the
endocytosis of CESAs. Genetic analysis between TWD40-2 and AP2M of the AP2
complex revealed that the roles of TWD40-2 in CME are both distinct from and
cooperative with the AP2 complex. Loss of efficient CME in twd40-2-3 resulted in
the unregulated overaccumulation of CESAs at the plasma membrane. In seedlings of
twd40-2-3 and other CME-deficient mutants, a direct correlation was revealed
between endocytic deficiency and cellulose content deficiency, highlighting the
importance of controlled CESA endocytosis in regulating cellulose biosynthesis.
PMID- 26417105
TI - Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense
by guanylate binding proteins.
AB - Many microbes create and maintain pathogen-containing vacuoles (PVs) as an
intracellular niche permissive for microbial growth and survival. The destruction
of PVs by IFNgamma-inducible guanylate binding protein (GBP) and immunity-related
GTPase (IRG) host proteins is central to a successful immune response directed
against numerous PV-resident pathogens. However, the mechanism by which IRGs and
GBPs cooperatively detect and destroy PVs is unclear. We find that host cell
priming with IFNgamma prompts IRG-dependent association of Toxoplasma- and
Chlamydia-containing vacuoles with ubiquitin through regulated translocation of
the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6
(TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and
deposition of GBPs to PVs, thereby conferring cell-autonomous immunity.
Hypervirulent strains of Toxoplasma gondii evade this process via specific
rhoptry protein kinases that inhibit IRG function, resulting in blockage of
downstream PV ubiquitination and GBP delivery. Our results define a ubiquitin
centered mechanism by which host cells deliver GBPs to PVs and explain how
hypervirulent parasites evade GBP-mediated immunity.
PMID- 26417108
TI - A parasitic nematode releases cytokinin that controls cell division and
orchestrates feeding site formation in host plants.
AB - Sedentary plant-parasitic cyst nematodes are biotrophs that cause significant
losses in agriculture. Parasitism is based on modifications of host root cells
that lead to the formation of a hypermetabolic feeding site (a syncytium) from
which nematodes withdraw nutrients. The host cell cycle is activated in an
initial cell selected by the nematode for feeding, followed by activation of
neighboring cells and subsequent expansion of feeding site through fusion of
hundreds of cells. It is generally assumed that nematodes manipulate production
and signaling of the plant hormone cytokinin to activate cell division. In fact,
nematodes have been shown to produce cytokinin in vitro; however, whether the
hormone is secreted into host plants and plays a role in parasitism remained
unknown. Here, we analyzed the spatiotemporal activation of cytokinin signaling
during interaction between the cyst nematode, Heterodera schachtii, and
Arabidopsis using cytokinin-responsive promoter:reporter lines. Our results
showed that cytokinin signaling is activated not only in the syncytium but also
in neighboring cells to be incorporated into syncytium. An analysis of nematode
infection on mutants that are deficient in cytokinin or cytokinin signaling
revealed a significant decrease in susceptibility of these plants to nematodes.
Further, we identified a cytokinin-synthesizing isopentenyltransferase gene in H.
schachtii and show that silencing of this gene in nematodes leads to a
significant decrease in virulence due to a reduced expansion of feeding sites.
Our findings demonstrate the ability of a plant-parasitic nematode to synthesize
a functional plant hormone to manipulate the host system and establish a long
term parasitic interaction.
PMID- 26417110
TI - Global transcriptional repression: An initial and essential step for Plasmodium
sexual development.
AB - Gametocytes are nonreplicative sexual forms that mediate malaria transmission to
a mosquito vector. They are generated from asexual blood-stage parasites that
proliferate in the circulation. However, little is known about how this
transition is genetically regulated. Here, we report that an Apetala2 (AP2)
family transcription factor, AP2-G2, regulates this transition as a
transcriptional repressor. Disruption of AP2-G2 in the rodent malaria parasite
Plasmodium berghei did not prevent commitment to the sexual stage but did halt
development before the appearance of sex-specific morphologies. ChIP-seq analysis
revealed that AP2-G2 targeted ~1,500 genes and recognized a five-base motif in
their promoters. Most of these target genes are required for asexual
proliferation of the parasites in the blood, suggesting that AP2-G2 blocks the
program that precedes asexual replication to promote conversion to the sexual
stage. Microarray analysis showed that the identified targets constituted ~70% of
the up-regulated genes in AP2-G2-depleted parasites, suggesting that AP2-G2
actually functions as a repressor in gametocytes. A promoter assay using a
centromere plasmid demonstrated that the binding motif functions as a cis-acting
negative regulatory element. These results suggest that global transcriptional
repression, which occurs during the initial phase of gametocytogenesis, is an
essential step in Plasmodium sexual development.
PMID- 26417109
TI - Minimal model for collective kinetochore-microtubule dynamics.
AB - Chromosome segregation during cell division depends on interactions of
kinetochores with dynamic microtubules (MTs). In many eukaryotes, each
kinetochore binds multiple MTs, but the collective behavior of these coupled MTs
is not well understood. We present a minimal model for collective kinetochore-MT
dynamics, based on in vitro measurements of individual MTs and their dependence
on force and kinetochore phosphorylation by Aurora B kinase. For a system of
multiple MTs connected to the same kinetochore, the force-velocity relation has a
bistable regime with two possible steady-state velocities: rapid shortening or
slow growth. Bistability, combined with the difference between the growing and
shrinking speeds, leads to center-of-mass and breathing oscillations in
bioriented sister kinetochore pairs. Kinetochore phosphorylation shifts the
bistable region to higher tensions, so that only the rapidly shortening state is
stable at low tension. Thus, phosphorylation leads to error correction for
kinetochores that are not under tension. We challenged the model with new
experiments, using chemically induced dimerization to enhance Aurora B activity
at metaphase kinetochores. The model suggests that the experimentally observed
disordering of the metaphase plate occurs because phosphorylation increases
kinetochore speeds by biasing MTs to shrink. Our minimal model qualitatively
captures certain characteristic features of kinetochore dynamics, illustrates how
biochemical signals such as phosphorylation may regulate the dynamics, and
provides a theoretical framework for understanding other factors that control the
dynamics in vivo.
PMID- 26417111
TI - Increased threat of tropical cyclones and coastal flooding to New York City
during the anthropogenic era.
AB - In a changing climate, future inundation of the United States' Atlantic coast
will depend on both storm surges during tropical cyclones and the rising relative
sea levels on which those surges occur. However, the observational record of
tropical cyclones in the North Atlantic basin is too short (A.D. 1851 to present)
to accurately assess long-term trends in storm activity. To overcome this
limitation, we use proxy sea level records, and downscale three CMIP5 models to
generate large synthetic tropical cyclone data sets for the North Atlantic basin;
driving climate conditions span from A.D. 850 to A.D. 2005. We compare pre
anthropogenic era (A.D. 850-1800) and anthropogenic era (A.D.1970-2005) storm
surge model results for New York City, exposing links between increased rates of
sea level rise and storm flood heights. We find that mean flood heights increased
by ~1.24 m (due mainly to sea level rise) from ~A.D. 850 to the anthropogenic
era, a result that is significant at the 99% confidence level. Additionally,
changes in tropical cyclone characteristics have led to increases in the extremes
of the types of storms that create the largest storm surges for New York City. As
a result, flood risk has greatly increased for the region; for example, the 500-y
return period for a ~2.25-m flood height during the pre-anthropogenic era has
decreased to ~24.4 y in the anthropogenic era. Our results indicate the impacts
of climate change on coastal inundation, and call for advanced risk management
strategies.
PMID- 26417112
TI - Reply to Lee: Downward bias in heritability estimation is not due to simplified
linkage equilibrium SNP simulation.
PMID- 26417113
TI - Implications of simplified linkage equilibrium SNP simulation.
PMID- 26417114
TI - A new level of regulation in gluconeogenesis: metabolic state modulates the
intracellular localization of aldolase B and its interaction with liver fructose
1,6-bisphosphatase.
AB - Understanding how glucose metabolism is finely regulated at molecular and
cellular levels in the liver is critical for knowing its relationship to related
pathologies, such as diabetes. In order to gain insight into the regulation of
glucose metabolism, we studied the liver-expressed isoforms aldolase B and
fructose-1,6-bisphosphatase-1 (FBPase-1), key enzymes in gluconeogenesis,
analysing their cellular localization in hepatocytes under different metabolic
conditions and their protein-protein interaction in vitro and in vivo. We
observed that glucose, insulin, glucagon and adrenaline differentially modulate
the intracellular distribution of aldolase B and FBPase-1. Interestingly, the in
vitro protein-protein interaction analysis between aldolase B and FBPase-1 showed
a specific and regulable interaction between them, whereas aldolase A (muscle
isozyme) and FBPase-1 showed no interaction. The affinity of the aldolase B and
FBPase-1 complex was modulated by intermediate metabolites, but only in the
presence of K(+). We observed a decreased association constant in the presence of
adenosine monophosphate, fructose-2,6-bisphosphate, fructose-6-phosphate and
inhibitory concentrations of fructose-1,6-bisphosphate. Conversely, the
association constant of the complex increased in the presence of dihydroxyacetone
phosphate (DHAP) and non-inhibitory concentrations of fructose-1,6-bisphosphate.
Notably, in vivo FRET studies confirmed the interaction between aldolase B and
FBPase-1. Also, the co-expression of aldolase B and FBPase-1 in cultured cells
suggested that FBPase-1 guides the cellular localization of aldolase B. Our
results provide further evidence that metabolic conditions modulate aldolase B
and FBPase-1 activity at the cellular level through the regulation of their
interaction, suggesting that their association confers a catalytic advantage for
both enzymes.
PMID- 26417115
TI - Robust Optimization of Biological Protocols.
AB - When conducting high-throughput biological experiments, it is often necessary to
develop a protocol that is both inexpensive and robust. Standard approaches are
either not cost-effective or arrive at an optimized protocol that is sensitive to
experimental variations. We show here a novel approach that directly minimizes
the cost of the protocol while ensuring the protocol is robust to experimental
variation. Our approach uses a risk-averse conditional value-at-risk criterion in
a robust parameter design framework. We demonstrate this approach on a polymerase
chain reaction protocol and show that our improved protocol is less expensive
than the standard protocol and more robust than a protocol optimized without
consideration of experimental variation.
PMID- 26417116
TI - Family and Teacher Characteristics as Predictors of Parent Involvement in
Education During Early Childhood Among Afro-Caribbean and Latino Immigrant
Families.
AB - Parent involvement is a robust predictor of academic achievement, but little is
known about school- and home-based involvement in immigrant families. Drawing on
ecological theories, the present study examined contextual characteristics as
predictors of parent involvement among Afro-Caribbean and Latino parents of young
students in urban public schools. Socioeconomic disadvantage was associated with
lower home-based involvement. Several factors were associated with higher
involvement, including parents' connection to their culture of origin and to U.S.
culture, engagement practices by teachers and parent-teacher ethnic consonance
(for Latinos only). Findings have implications for promoting involvement among
immigrant families of students in urban schools.
PMID- 26417117
TI - Microstructures and superconducting properties of high performance MgB2 thin
films deposited from a high-purity, dense Mg-B target.
AB - High quality, c-axis oriented, MgB2 thin films were successfully grown on 6H-SiC
substrates using pulsed laser deposition (PLD) with subsequent in situ annealing.
To obtain high purity films free from oxygen contamination, a dense Mg-B target
was specially made from a high temperature, high pressure reaction of Mg and B to
form large-grained (10~50 um) MgB2. Microstructural analysis via electron
microscopy found that the resulting grains of the film were composed of ultrafine
columnar grains of 19-30 nm. XRD analysis showed the MgB2 films to be c-axis
oriented; the a-axis and c-axis lattice parameters were determined to be 3.073 +/
0.005 A and 3.528 +/- 0.010 A, respectively. The superconducting critical
temperature, Tc,onset , increased monotonically as the annealing temperature was
increased, varying from 25.2 K to 33.7 K. The superconducting critical current
density as determined from magnetic measurements, Jcm , at 5 K, was 105 A/cm2 at
7.8 T; at 20 K, 105 A/cm2 was reached at 3.1 T. The transport and pinning
properties of these films were compared to "powder-in-tube" (PIT) and "internal
infiltration" (AIMI) processed wires. Additionally, examination of the pinning
mechanism showed that when scaled to the peak in the pinning curve, the films
follow the grain boundary, or surface, pinning mechanism quite well, and are
similar to the response seen for C doped PIT and AIMI strands, in contrast to the
behavior seen in undoped PIT wires, in which deviations are seen at high b (b =
B/Bc2 ). On the other hand, the magnitude of the pinning force was similar for
the thin films and AIMI conductors, unlike the values from connectivity
suppressed PIT strands.
PMID- 26417118
TI - A comparative study between intrathecal dexmedetomidine and fentanyl as adjuvant
to intrathecal bupivacaine in lower abdominal surgeries: A randomized trial.
AB - CONTEXT: Spinal anesthesia is preferred choice of anesthesia in lower abdominal
surgeries since long time. However problem with this is limited duration of
action, so for long duration surgeries alternative are required. Dexmedetomidine
is a highly selective alpha-2-adrenergic agonist has property to potentiate the
action of local anesthetic used in spinal anesthesia. Fentanyl is an opioid and
it has also the same property. AIMS: To compare the efficacy, analgesic effects,
and side-effects of dexmedetomidine and fentanyl as adjuvant to bupivacaine for
lower abdominal surgery. SETTINGS AND DESIGN: The type of this study was double
blind randomized trial. SUBJECTS AND METHODS: A total of 80 patients were
randomly allocated in two Group D and Group F. Group D were injected injection
bupivacaine 0.5% heavy * 3.0 ml + 0.5 ml of preservative free normal saline
containing 5 MUg dexmedetomidine. Group F were received injection bupivacaine
0.5% heavy * 3.0 ml + 0.5 ml fentanyl equivalent to 25 MUg. STATISTICAL ANALYSIS
USED: The statistical analysis was performed using SPSS (Statistical Package for
Social Sciences) version 15.0 statistical analysis software. RESULTS: The results
show that highest sensitivity level of T6 and T8 was achieved by higher
proportion of subjects from Group D when compared to Group F and sensitivity
level T7 was achieved by higher proportion of subjects of Group F when compared
to Group D. Duration of analgesic properties was significantly higher in Group D
when compared to Group F. CONCLUSION: The findings in the present study suggested
that intrathecal adjuvant use of dexmedetomidine as compared to fentanyl provides
a longer sensory and motor blockade and also prolongs the postoperative analgesic
effect.
PMID- 26417119
TI - A prospective randomized controlled study comparing intrathecal bupivacaine
combined with fentanyl and sufentanil in abdominal and lower limb surgeries.
AB - BACKGROUND: Hyperbaric bupivacaine along with either fentanyl or sufentanil as
additive, has been widely used in spinal anesthesia. In the present study, we
compared the analgesic effects of intrathecal fentanyl versus sufentanil combined
with bupivacaine for surgical procedures over the abdomen and lower limbs.
SETTINGS AND DESIGN: This was randomized controlled study conducted in a tertiary
care hospital attached to a medical school. METHODS: Sixty American Society of
Anesthesiologists I and II patients were randomized into three groups by sealed
envelope technique. Group 1 was to receive bupivacaine with fentanyl; group 2 to
receive bupivacaine with sufentanil and group 3 to receive bupivacaine with
saline (control), intrathecally. The parameters checked were hemodynamic changes,
onset and duration of sensory block, duration of analgesia and maximal sensory
level achieved. STATISTICAL ANALYSIS: The data collected were analyzed using chi2
test and paired Student's t-test. RESULTS: The time taken for the onset of
analgesia was longest in the control group followed by fentanyl group. The
earliest onset of action of 9.35 +/- 1.92 min was recorded in sufentanil group.
Duration of sensory blockade and analgesia was longest for fentanyl group than
the other groups. Adverse effects noted were more for sufentanil group but were
self-limiting. CONCLUSION: Fentanyl with bupivacaine produced prolonged analgesia
and delayed two-segment regression and demonstrated reduced incidence of
complications as compared with intrathecal sufentanil. As the quality of
analgesia was complete and comparable, fentanyl emerges as a better option for
analgesia and it is much economical too when compared to sufentanil.
PMID- 26417120
TI - Comparative evaluation of cost effectiveness and recovery profile between
propofol and sevoflurane in laparoscopic cholecystectomy.
AB - BACKGROUND: Anesthetic agents should be chosen not only on the basis of safety
efficacy profile, but also on the economic aspect. Propofol and sevoflurane are
commonly utilized anesthetic agent for general anesthesia. AIM: The present study
was designated to compare cost-effectiveness and recovery profile between
propofol and sevoflurane for induction, maintenance or both. SETTINGS AND DESIGN:
Randomized controlled, participant and data operator blinded trial. MATERIALS AND
METHODS: Ninety patients undergoing laparoscopic cholecystectomy were randomized
into three equal groups to receive: Group P to receive injection propofol for
both induction and maintenance; Group PS to receive injection propofol for
induction and sevoflurane for maintenance; and Group S to receive sevoflurane for
both induction and maintenance of general anesthesia, respectively. Cost
analysis, hemodynamic parameter, and recovery profile were compared between these
groups. STATISTICAL ANALYSIS: One-way analysis of variance test or Fisher's exact
test/Chi-square test whichever appropriate. RESULTS: Total cost of anesthesia was
highest in Group P and lowest in Group S. Mean time to extubation and time to
follow verbal commands was lowest in Group S than Group P or Group P/S.
Hemodynamic parameter was more stable in Group S. CONCLUSION: We conclude that
sevoflurane appears to be better anesthetic agents in terms of cost-effectiveness
and recovery profile.
PMID- 26417121
TI - Effect of preoperative pregabalin on postoperative pain relief in thyroidectomy
patients: A prospective observational study.
AB - BACKGROUND: Effective management of postoperative pain leads to increased patient
satisfaction, earlier mobilization, reduced hospital stay and costs. One of the
methods used for management of postoperative pain is preemptive analgesia
blockade of afferent nerve fibers before a painful stimulus. It modifies
peripheral and central nervous system processing of noxious stimuli and reduces
postoperative opioid consumption. In this study, we sought to determine whether
the preoperative use of pregabalin reduced postoperative pain and morphine
consumption in thyroidectomy. MATERIALS AND METHODS: The observation was
conducted on patients undergoing thyroidectomy surgery in two groups of 30 each.
Of the two groups, one received a single oral dose of pregabalin 1 h
preoperatively. Both the group of patients undergoes anesthesia in a similar
manner. Following surgery the efficacy of the preoperative dose of pregabalin is
observed by measuring the total opioid consumption 6 h postoperatively and
assessing verbal numeric pain scales. RESULTS: The mean time to request of rescue
analgesia in pregabalin group was 322.07 +/- 69.106 min when compared to morphine
group 256.33 +/- 111.978 min (P < 0.05). The mean pain scores in the
postoperative period were also significantly lower in patients receiving
pregabalin. CONCLUSION: Single oral dose of pregabalin was effective in reducing
acute postoperative pain in thyroidectomy patients. It prolongs the time to the
request of rescue analgesia and also results in lower postoperative pain scores
in the immediate postoperative period. However a statistically significant low
opioid consumption could not be proved.
PMID- 26417122
TI - A study to compare the overall effectiveness between midazolam and
dexmedetomidine during monitored anesthesia care: A randomized prospective study.
AB - BACKGROUND: Monitored anesthesia care (MAC) combines intravenous sedation along
with local anesthetic infiltration or nerve block. Several drugs have been used
for MAC, but all are associated with complications. Dexmedetomidine is a
selective alpha2-adrenoceptor agonist with both sedative and analgesic properties
and is devoid of respiratory depressant effects. Its short elimination half-life
makes it an attractive agent for sedation during MAC. AIM: Comparative evaluation
of dexmedetomidine and midazolam for MAC. METHODS: In this prospective,
randomized, double-blind study, 50 American Society of Anesthesiologist I and II
patients undergoing a surgical or diagnostic procedure of <1 h requiring MAC were
enrolled. Dexmedetomidine-ketamine (Group "KD") patients (n = 25) received
intravenous (I.V.) dexmedetomidine 1 mcg/kg over 10 min followed by 0.5 mg/kg of
I.V. ketamine. Midazolam-ketamine patients (n = 25) received I.V. midazolam 0.05
mg/kg over 10 min followed by 0.5 mg/kg of I.V. ketamine to get a targeted level
of sedation (<=4 using Observer's Assessment of Alertness/Sedation Scale score).
Inadequate sedation (e.g., 15% increase in mean arterial blood pressure or heart
rate, decrease in degree of calmness, increase in respiratory rate, physical
movement) was treated by a ketamine bolus of 0.5 mg/kg as a rescue analgesia.
STATISTICAL ANALYSIS: The statistical tests used in the study are unpaired
Student's t-test for continuous variables and Chi-square test for categorical
variables. Mann-Whitney test was used to assess the patient and surgeon
satisfaction. Data were expressed as mean +/- standard deviation. Value of P <
0.05 is considered significant and P < 0.0001 as highly significant. RESULTS:
Clinically desired sedation and analgesia was achieved earlier and better with
dexmedetomidine. Patients and surgeons satisfaction were significantly higher
with dexmedetomidine. The requirement of additional sedation and analgesia was
less in dexmedetomidine (KD) group. CONCLUSION: During MAC dexmedetomidine
provides better sedation and analgesia than midazolam.
PMID- 26417123
TI - Effects of isobaric ropivacaine with or without fentanyl in subarachnoid
blockade: A prospective double-blind, randomized study.
AB - BACKGROUND: The addition of fentanyl to ropivacaine has shown to improve the
quality of analgesia without compromising its benefits such as early mobilization
and early voiding. AIM: The aim of the study was to evaluate the effects of the
isobaric ropivacaine in combination with fentanyl and compare it with the
isobaric ropivacaine alone in spinal anesthesia for lower abdominal and lower
limb surgeries. SETTINGS AND DESIGN: Double-blinded randomized controlled trial.
SUBJECTS AND METHODS: Hundred patients belonging to American Society of
Anesthesiologists physical status I and II scheduled for either lower abdominal
or lower limb surgery under spinal anesthesia were included. The study was a
prospective double-blinded randomized controlled trial where patients were
randomly allocated into two groups to receive either 2.5 ml of 0.75% (18.75 mg)
isobaric ropivacaine with 25 MUg fentanyl (Group RF) or 2.5 ml of 0.75% (18.75
mg) isobaric ropivacaine with 0.5 ml of 0.9% saline (Group R) intrathecally.
STATISTICAL ANALYSIS: Data analysis was done by Student's unpaired t-test. SPSS
version 16 was used. P < 0.05 was considered as statistically significant.
RESULTS: We found no significant difference in hemodynamics, onset of sensory and
motor block, peak level of block, recovery from motor block, return of
micturition and incidence of side effects with the addition of fentanyl to
ropivacaine. First request for analgesia was required earlier in the control
group. There was also a significant prolongation of the duration of sensory block
(mean - 341.6 min) and postoperative analgesia in Group RF (mean - 442.2 min) (P
< 0.001). CONCLUSION: The addition of fentanyl to ropivacaine significantly
prolongs the duration of postoperative analgesia with clinically insignificant
influence on hemodynamics and motor blockade with minimal side effects.
PMID- 26417124
TI - Comparison of levobupivacaine and levobupivacaine with fentanyl in infraumbilical
surgeries under spinal anaesthesia.
AB - BACKGROUND: Intrathecal opioids added to low dose local anesthetics in spinal
anaesthesia intensifies sensory block without affecting sympathetic blockade. Aim
was to evaluate the safety and efficacy of intrathecal levobupivacaine plain
versus levobupivacaine plus fentanyl in infraumbilical surgeries. MATERIALS AND
METHODS: In a prospective randomized double blind study, 100 patients of American
Society of Anesthesiologists grades I and II of either sex, 20-65 years of age
were included after approval from the Ethics Committee. Informed consent was
taken and patients were randomly divided into two groups of 50 each, to receive
either 2 ml of 0.5% isobaric levobupivacaine (group L) or 2 ml of 0.5% isobaric
levobupivacaine + 25 MUg fentanyl (group LF) intrathecally. Patients were
monitored for sensory and motor block characteristics, postoperative analgesia,
haemodynamics and side effects and complications for 24 h. RESULTS: Onset of
sensory block and time to maximum sensory block was rapid in group LF (4.8 +/-
1.50 and 8.46 +/- 1.87 min) as compared to group L (7.6 +/- 1.46 and 15.80 +/-
2.43 min) (P < 0.000). Maximum sensory block was T6 in group LF and T8 in group
L. Maximum Bromage score was 2 in both groups but was achieved earlier in group
LF (P < 0.000). Duration of sensory and motor block was significantly prolonged
in group LF (270.98 +/- 28.60 and 188.52 +/- 9.81 min) as compared to group L
(197.58 +/- 11.20 and 152.76 +/- 9.79 min). Total duration of analgesia was also
prolonged in group LF (265.16 +/- 26.18 min) as compared to group L (168.16 +/-
11.08 min). Patients remained haemodynamically stable and side effects and
complications were comparable in both groups. Data was analyzed using "Chi-square
test" and "unpaired t-test." CONCLUSION: Addition of fentanyl to levobupivacaine
leads to early onset and prolonged duration of sensory and motor block as well as
postoperative analgesia with stable haemodynamics and minimal side effects.
PMID- 26417125
TI - A comparative study-efficacy and safety of combined spinal epidural anesthesia
versus spinal anesthesia in high-risk geriatric patients for surgeries around the
hip joint.
AB - CONTEXT: Combined spinal epidural anesthesia (CSEA) has a significant advantage
by enabling the use of low dose intrathecal local anesthetic, with knowledge that
the epidural catheter may be used to extend the block as necessary. CSEA is
useful in high-risk geriatric patients by providing greater hemodynamic
stability. AIM: This study is designed to compare the clinical effects of CSEA
versus spinal anesthesia in high-risk geriatric patients undergoing surgeries
around the hip joint. MATERIALS AND METHODS: Sixty patients aged >65 years,
American Society of Anaesthesiology III and IV were randomly allocated into two
equal groups. Group A (n = 30) received CSEA with 1 ml (5 mg) of 0.5% hyperbaric
bupivacaine with 25 MUg fentanyl through spinal route, and the expected
incompleteness of spinal block was managed with small incremental dose of 0.5%
isobaric bupivacaine through epidural catheter, 1-1.5 ml for every unblocked
segment to achieve T10 sensory level. Group B (n = 30) received spinal anesthesia
with 2.5 ml (12.5 mg) of 0.5% hyperbaric bupivacaine and 25 MUg fentanyl. RESULT:
Both the groups showed rapid onset, excellent analgesia and good quality motor
block. Group A showed a significantly less incidence of hypotension (P < 0.01)
along with the provision of prolonging analgesia as compared to Group B.
CONCLUSION: CSEA is a safe, effective, reliable technique with better hemodynamic
stability along with the provision of prolonging analgesia compared to spinal
anesthesia for high-risk geriatric patients undergoing surgeries around the hip
joint.
PMID- 26417126
TI - Comparative evaluation of 0.75% ropivacaine with clonidine and 0.5% bupivacaine
with clonidine in infraclavicular brachial plexus block.
AB - BACKGROUND: Infraclavicular brachial block with coracoids approach has gained
popularity because of consistent bony landmarks and less chances of vascular
puncture and pneumothorax. AIM: The aim of this study was to evaluate the effect
of adding clonidine to bupivacaine or ropivacaine on the onset and duration of
sensory and motor block and duration of analgesia in infraclavicular block.
MATERIALS AND METHODS: In a prospective randomized double-blind study, 60
patients of 18-65 years were randomly divided in to two groups of 30 each.
Infraclavicular block was performed with 30 ml of 0.75% ropivacaine + 150 MUg
clonidine in group R and 30 ml of 0.5% bupivacaine + 150 MUg clonidine in group B
and were compared for onset and duration of sensory and motor block,
postoperative analgesia, side-effects and complications. RESULTS: Significant
differences were observed in the time for onset of sensory block (5.80 +/- 5.12
min in group R and 4.87 +/- 1.46 min in group B, P < 0.05); onset of motor block
(11.37 +/- 2.66 min in group R and 9.60 +/- 1.78 min in group B, P < 0.05);
duration of sensory and motor block (10.07 +/- 0.91 and 9.03 +/- 0.89 h in group
R and 12.50 +/- 1.14 and 10.67 +/- 1.18 h in group B respectively, P < 0.01) and
duration of analgesia (15.30 +/- 1.39 h in group R and 18.07 +/- 1.66 h in group
B). No significant difference was observed in hemodynamics, sedation, side
effects and complications. STATISTICAL ANALYSIS: Variables were compared using
Chi-square test for nonparametric data and Student's t-test for parametric data.
CONCLUSION: Addition of clonidine to bupivacaine lead to early onset and
prolonged duration of sensory and motor block with prolonged analgesia as
compared to the addition of clonidine to ropivacaine.
PMID- 26417127
TI - A comparative study of intrathecal clonidine and dexmedetomidine on
characteristics of bupivacaine spinal block for lower limb surgeries.
AB - INTRODUCTION: Intrathecal clonidine or dexmedetomidine has improved the quality
of spinal anesthesia, this clinical study was undertaken to assess the behavior
of intrathecal clonidine as an adjuvant to bupivacaine in augmenting sensory
block in patients undergoing lower limb surgeries. MATERIALS AND METHODS: We
studied 150 patients, between 18 and 60 years of age, patients were randomly
divided into three groups of 50 each Group B: 0.5% bupivacaine 15 mg + 0.5 ml
normal saline Group C: 0.5% bupivacaine 15 mg + 50 MUg clonidine Group D: 0.5%
bupivacaine 15 mg + 5 MUg dexmedetomidine. Onset and duration of sensory block
and motor block, the highest level of sensory blockade, duration of analgesia,
and side-effects were assessed. RESULTS: The onset of motor block was faster in
Group C and Group D as compared to Group B, The time to reach Bromage scale 3 was
fastest in Group C followed by Group D P < 0.001. The duration of sensory, motor
blockade and duration of analgesia was longer in Groups C and D as compared to
Group B, longest in Group D followed by C and B. The time to regression time to
S1 dermatome was. It was longest in Group D followed by Group C and then Group B.
Intergroup comparison B to C, B to D and C to D was significant. Duration of
analgesia was significantly prolonged in Group C and Group D (P < 0.001) with a
mean duration of 309.6 +/- 50.99 min in Group C and 336.8 +/- 55.38 min in Group
D as compared to 204.8 +/- 16.81 min in Group B. Intergroup comparison B to C, B
to D and Group C to D was significant. Duration was longest in Group D followed
by Group C and then Group B. CONCLUSION: Supplementation of bupivacaine spinal
block with a low dose of intrathecal dexmedetomidine (5 MUg) or clonidine (50
MUg) produces a significantly shorter onset of motor and sensory block and a
significantly longer sensory and motor block than bupivacaine alone.
PMID- 26417128
TI - Caudal-epidural bupivacaine versus ropivacaine with fentanyl for paediatric
postoperative analgesia.
AB - BACKGROUND AND AIMS: Caudal-epidural, the most commonly used regional analgesia
technique, is virtually free of measurable hemodynamic effects, thus adding a new
dimension to the evolving necessity of pediatric postoperative pain management.
Though, bupivacaine is the most commonly used drug for this purpose, ropivacaine
has emerged as a safer alternative, with the addition of opioids, like fentanyl,
increasing the effective duration of analgesia. With this overview, our present
study was designed to compare the postoperative analgesic efficacy of bupivacaine
fentanyl and ropivacaine-fentanyl combinations by caudal-epidural technique in
pediatric infraumbilical surgeries. MATERIALS AND METHODS: Totally, 60 pediatric
patients, of either sex, aged between 2 and 8 years, American Society of
Anesthesiologists physical status I and II, undergoing elective infraumbilical
surgeries were assigned into two groups, Group BF receiving bupivacaine 0.25%,
0.7 ml/kg and Group RF receiving ropivacaine 0.25%, 0.7 ml/kg with fentanyl 1
MUg/kg added to each group. Assessment of pain was done using "Hannallah pain
scale." Consumption of the total amount of rescue analgesic and time to
requirement of the first dose, as also duration of motor blockade were noted.
Perioperative hemodynamics and any adverse effects were monitored at regular
intervals. RESULTS: The RF Group experienced significantly longer duration of
effective postoperative analgesia, with significantly shorter duration of motor
blockade and lesser total analgesic requirement in comparison to the BF Group.
Hemodynamically, patients in both the groups, were equally stable. CONCLUSION:
Ropivacaine, with an equipotent analgesic efficacy and a lesser duration of motor
block, can be used as an alternative to bupivacaine for pediatric postoperative
pain care through the caudal route.
PMID- 26417129
TI - A comparison of intranasal ketamine and intranasal midazolam for pediatric
premedication.
AB - AIMS AND OBJECTIVES: The aim of our study is to compare the efficacy and side
effects of Ketamine and Midazolam administered nasally for the pediatric
premedication. MATERIALS AND METHODS: We studied 100 American Society of
Anesthesiology I and II children aged from 1 to 10 years undergoing various
surgical procedures. Totally, 50 children were evaluated for nasal ketamine
(using 50 mg/ml vials) at the dose of 5 mg/kg and the other 50 received nasal
midazolam 0.2 mg/kg, before induction in operation theater each patient was
observed for onset of sedation, degree of sedation, emotional status being
recorded with a five point sedation scale, response to venipuncture and
acceptance of mask, whether readily, with persuasion or refuse. RESULTS: The two
groups were homogenous. Midazolam showed a statistically significant early onset
of sedation (10.76 +/- 2.0352 vs. 16.42 +/- 2.0696 min). There were no
significant differences in venipuncture score, sedation scale at 20 min,
acceptance of mask and oxygen saturation throughout the study. Significant
tachycardia and 'secretions were observed in the ketamine group intra
operatively. Postoperatively emergence (8% vs. 0%) and secretions (28% vs. 4%)
were significant in the ketamine group. Nausea and vomiting occurred in l6%
versus 10% for midazolam and ketamine group. CONCLUSIONS: Both midazolam and
ketamine nasally are an effective pediatric premedication. Midazolam has an early
onset of sedation and is associated with fewer side-effects.
PMID- 26417130
TI - Efficacy of alpha2 agonists in obtunding rise in intraocular pressure after
succinylcholine and that following laryngoscopy and intubation.
AB - CONTEXT: Elevation of intraocular pressure (IOP) is an inherent and inadvertent
association with the use of succinylcholine and alpha2 agonists can be used to
obtund this effect. AIMS: The study was aimed to assess the efficacy of
intravenous dexmedetomidine and clonidine premedication in attenuating rise in
IOP during laryngoscopy and intubation following administration of
succinylcholine. SETTINGS AND DESIGN: This prospective, observational study was
conducted in 40 patients aged 20-60 years undergoing non ophthalmic surgical
procedures. SUBJECTS AND METHODS: For patients in Group D, dexmedetomidine 0.4
mcg/kg and in Group C clonidine 1 MUg/kg over 10 min was administered before
induction. All patients were induced with propofol. Laryngoscopy and intubation
were performed 1 min after administration of succinylcholine 2 mg/kg. STATISTICAL
ANALYSIS USED: Mann-Whitney, Chi-square and Wilcoxon tests. RESULTS: Mean
baseline IOP of both groups were comparable (15.4 +/- 2.6 vs. 14.7 +/- 2.3).
Following premedication and induction, IOP decreased in both groups and the
reduction was significantly more in Group D. Following administration of
succinylcholine and 1 min after intubation IOP raised and exceeded the baseline
value in Group C (16.0 +/- 1.6 and 18.6 +/- 2.2). Though there was an increase in
IOP in Group D (12.0 +/- 1.9 and 14.0 +/- 2.1), it did not reach up to baseline
values. Then there was a gradual reduction in IOP in both groups at 3, 5, and 10
min and Group D continued to have a significantly low IOP than Group C up to 10
min. CONCLUSIONS: Dexmedetomidine 0.4 MUg/kg resulted in a reduction of IOP and
blunted the increase in IOP, which followed administration of succinylcholine,
laryngoscopy, and intubation. Though clonidine 1 MUg/kg reduced IOP, it did not
prevent rise in IOP following succinylcholine, laryngoscopy, and intubation.
PMID- 26417131
TI - Motor response evaluation during brachial plexus block anesthesia: An
ultrasonography aided study.
AB - BACKGROUND: The sparing of ulnar nerve often leads to the failure of the upper
limb blockade. It has been claimed that local anesthetic injection at the site of
stimulator evoked finger flexion response is associated with highest success rate
of a successful block. The lower trunk stimulation of plexus should yield similar
results as this trunk contributes significantly for median and ulnar nerves of
hand and forearm. MATERIALS AND METHODS: The patients with intact anatomical
upper limb structures underwent (a) combined ultrasound (USG) assisted nerve
stimulator evoked motor response evaluation or in (b) open brachial plexus trunk
stimulation evaluations. The individual patient's lower trunk stimulation motor
responses were documented. RESULTS: When combined the results of both USG and
open plexus groups, wrist flexion was seen in 52%, finger flexion in 61% and
forearm pronation or twitches of anterior compartment in 48% of total subjects
studied. These responses were noted either separately or in combinations.
CONCLUSION: We conclude other than finger flexion, the wrist flexion the forearm
twitches, pronation and wrist adduction may be used for lower trunk blockade and
thus for higher accuracy.
PMID- 26417132
TI - Effects of different types of pharyngeal packing in patients undergoing nasal
surgery: A comparative study.
AB - CONTEXT: Postoperative throat complaints such as postoperative sore throat
(POST), dysphagia, and hoarseness frequently arises after tracheal intubation and
throat packing for patient undergoing general anesthesia. This condition is very
disturbing to patient. Avoiding POST is a major priority for these patients
because preventing postoperative complications contributes to patient
satisfaction. AIMS: To describe and analyze the postoperative throat effects of
nasopharyngeal packing and oropharyngeal packing in patients undergoing nasal
surgery. SETTINGS AND DESIGN: A randomized comparative study. SUBJECTS AND
METHODS: After obtaining approval of Ethical Committee 40 patients were included
in study. After this patient were randomly allocated into two groups of 20 each.
Group A - in which the oropharynx was packed and Group B - inwhich the
nasopharynx was packed. General anesthesia were given and throat packing was done
and patients were interviewed postoperatively for any throat complications such
as sore throat, difficulty in swallowing (dysphagia), hoarseness of voice, throat
irritation, and any other symptom pertaining to the study were noted and data
were analyzed. STATISTICAL ANALYSIS USED: T-test to compare the age, while Chi
square test and Fisher's exact test were used to compare sex distribution, sore
throat, dysphagia, hoarseness, and throat irritation. RESULTS: Results showed
statistically significant difference in incidence and severity of POST in Group A
patients when compared to Group B patients to be more. Patients in Group A had a
higher incidence of dysphagia when compared to their Group B counterparts. With
respect to the incidence of hoarseness and throat irritation, there was no
statistical significance between the groups. CONCLUSION: We concluded that the
site of pharyngeal packing influences the incidence and severity of POST and as
well as the incidence of dysphagia after general anesthesia. The use of
nasopharyngeal packing in the patients undergoing nasal surgeries might lead to a
reduction of the same.
PMID- 26417133
TI - Anesthetic management of a newborn with occipital meningocele for magnetic
resonance imaging.
AB - Cranial Meningocoele is a term which represents herniation of meninges and
cerebrospinal fluid through the congenital defect in the cranium. Anaesthetic
challenges in the management of neonates with occipital meningocoele include
airway management and proper positioning of the neonate without pressure on the
meningocoele sac so as to preventthe rupture of the membranes. Associated
congenital anomalies also can cause anaesthesia and procedure related
complications. Other difficulties include performing a difficult airway case in
an unfamiliar environment outside operation theatre. We report a case of 6 day
old neonate with occipital meningocoele posted for MRI brain and the successful
anaesthetic management.
PMID- 26417134
TI - Unusual but completely avoidable complication during central venous
catheterization.
AB - Central venous catheterization is generally a safe procedure, but several
complications such as pneumothorax, arrhythmias, arterial puncture, infection,
and thrombosis are known to occur even in the experienced hands. Complications
related to guide wire are very rare and mostly relate to the expertise of
operating person. We hereby report a rare but completely avoidable complication,
that is, complete loss of the guide wire into the subclavian vein which was
successfully retrieved by surgery.
PMID- 26417135
TI - I-gel saves the day: Bradycardia and apnea in a patient undergoing burr hole and
evacuation for a subdural hematoma under scalp block.
AB - Awake craniotomy is generally performed in scalped block, although it is safe,
but this procedure can sometimes produce severe hemodynamic disturbances. Here,
we reported a case of 32-year-old male, who came for burr hole and during the
craniotomy performed under scalped block developed bradycardia and became apneic
as manifested by the absence of ETCO2 and no chest excursions. An I-gel was
inserted rather than intubating the patient and the case was managed very well
and which showed the importance of supraglottic airway devices in our day to day
practice.
PMID- 26417136
TI - Difficult airway challenges-intubation and extubation matters in a case of large
goiter with retrosternal extension.
AB - Thyroid diseases have an anesthetic implication that includes difficult airway
management, uncontrolled hyperthyroidism, hypothyroidism and postthyroidectomy
complications. Securing airway: Intubation and extubation both require skillful
management and timely decision to reduce morbidity and mortality in the case of
large goiter with retrosternal extension that leads to tracheal compression and
deviation. We present the anesthetic management in a patient with a large goiter
with retrosternal extension leading to tracheal compression and deviation. We
managed the case with an awake fiberoptic intubation and guided extubation.
PMID- 26417137
TI - Management of bilateral recurrent laryngeal nerve paresis after thyroidectomy.
AB - Bilateral recurrent laryngeal nerve (RLN) injury is rare for benign thyroid
lesions (0.2%). After extubation-stridor, respiratory distress, aphonia occurs
due to the closure of the glottic aperture necessitating immediate intervention
and emergency intubation or tracheostomy. Intra-operative identification and
preservation of the RLN minimizes the risk of injury. It is customary to expect
RLN problems after thyroid surgery especially if malignancy, big thyroid,
distorted anatomical problems and difficult airway that can lead to intubation
trauma. Soon after extubating, it is essential to the anesthetist to check the
vocal cord movements on phonation and oropharyngeal reflexes competency. But this
case is specially mentioned to convey the message that in spite of absence of
above mentioned predisposing factors for complications and good recovery profile
specific to thyroid, there can be unanticipated airway compromise that if not
attended to immediately may cost patient's life. This is a case of postextubation
stridor following subtotal thyroidectomy due to bilateral RLN damage and its
management.
PMID- 26417138
TI - Malpositioning of central venous cannula inserted through internal jugular vein
after failed cannulation through ipsilateral subclavian vein.
AB - The anesthesiologist is frequently involved in the task of achieving central
venous access either for intraoperative uses or postoperative purposes or
Intensive Care Unit care. We are usually aware of the common complications of
subclavian approach, such as arterial puncture, bleeding, pneumothorax,
misplacement in the ipsilateral internal jugular vein (IJV) or contralateral
brachiocephalic or subclavian vein. In this case report, we highlight the
possibility of malpositioning of central venous cannula inserted through IJV into
the anterior extra pleural plane after failed subclavian cannulation attempts.
PMID- 26417139
TI - Management of atypical eclampsia with intraventricular hemorrhage: A rare
experience and learning!
AB - Cerebrovascular accident during hypertensive disorder of pregnancy is a rare
entity, but carries high risk of mortality and morbidity due to its unpredictable
onset and late diagnosis. Here, we report an unusual case of 20-year-old
primigravida with 34 weeks gestation having no risk factor, which developed
sudden atypical eclampsia and intracranial hemorrhage within few hours. She was
successfully managed by multidisciplinary approach including emergency cesarean
section and conservative neurological treatment for intraventricular hemorrhage.
PMID- 26417141
TI - Electrocardiographic changes after lung resection: Case report and brief review.
AB - The incidence of acute coronary syndrome after a lung resection is less,
especially in an asymptomatic patient. However, arrhythmias are very commonly
encountered which can be benign or may require anti-arrhythmic agents thereby
increasing stay postoperatively in the Intensive Care Unit. We encountered
unexpected ST-T changes after a left upper lobectomy under general anesthesia in
a 60-year-old lady in the immediate postoperative period that made us to review
the literature for electrocardiographic abnormalities after lung resection
surgeries.
PMID- 26417140
TI - Obstruction of a non-resterilized reinforced endotracheal tube during craniotomy
under general anesthesia.
AB - Many cases of reinforced endotracheal tube (ETT) obstruction were reported in the
literature. In most of these cases, the obstruction was related to the use of a
resterilized tube with or without the use of nitrous oxide (N2O). Resterilization
and autoclaving of the tube may result in dissection or formation of a bleb
between the two layers of the tube that may expand after the use of N2O. We
describe a case of acute non-resterilized reinforced ETT obstruction, by bleb
formation, during occipital craniotomy under general anesthesia.
PMID- 26417142
TI - Anaesthetic management of beta thalassemia major with hypersplenism for
splenectomy in pediatric age group: Report of four cases.
AB - Beta thalassemia is the most common cause of hemolytic anemia in India. Hereby we
are reporting four cases of beta thalassemia major aged between 5 and 10 years
posted for splenectomy over a period of 2 months. These patients were on repeated
blood transfusions since the day of diagnosis, and two patients had a history of
cardiac failure. In addition to emphasizing the anesthetic challenges, the
purpose of reporting such cases is to raise the awareness of the disease and
prevention of the same by aggressive screening and prenatal diagnosis.
PMID- 26417143
TI - Anesthetic management of a large cystic hygroma in a newborn.
AB - Cystic hygroma is a congenital benign tumor occurring due to the accumulation of
lymph and during its anesthetic management difficulties are known to be
encountered. A newborn baby presented with a massive swelling in the front of the
neck. It was an antenatally diagnosed case of cystic hygroma with intraoral
extension proving to be an anticipated difficult airway. Following inhalational
induction, mask ventilation was possible, and the child was successfully
intubated. Intra-operative period was uneventful, and the tumor was completely
excised. Postoperatively, the child was ventilated for 24 h in view of
anticipated airway edema.
PMID- 26417144
TI - Cardiac arrest following butane inhalation.
AB - Butane is a commonly misused volatile agent, and a cause of intoxication. We
present a case, who had a syncope and persistent ventricular fibrillation during
the course of resuscitation. We discussed the management of this case in the
intensive care unit and the accompanying difficulties in the light of the current
literature.
PMID- 26417146
TI - Fixation of bilateral condylar fractures with maxillary and mandibular nerve
blocks.
AB - Mandibulo facial injuries present special problems to the anesthesiologist in
terms of the difficult airway. Hence, if regional anesthesia could be possible,
it necessarily removes the major concern with airway access. We present a case of
bilateral mandibular condylar fracture dislocation with the maxillary and
mandibular nerve blocks on both sides. The surgery went on smoothly without any
perioperative problems.
PMID- 26417145
TI - The anesthetic considerations while performing supraclavicular brachial plexus
block in emergency surgical patients using a nerve stimulator.
AB - Regional anesthesia is favored in patients who undergo emergency extremity (limb)
surgery, and specifically so in the absence of fasting status. In the absence of
ultrasonic guidance, the nerve stimulator still remains a valuable tool in
performing a brachial block, but its use is difficult in an emergency surgical
patient and greater cautious approach is essential. We identified the
supraclavicular plexus by the nerve stimulation-motor response technique as
follows. Anterior chest muscles contractions, diaphragmatic contraction, deltoid
contractions, and posterior shoulder girdle muscle contractions when identified
were taken as "negative response" with decreasing stimulating current. A forearm
muscle contraction, especially "wrist flexion" and "finger flexion" at 0.5 mA of
current was taken as "positive response." If no positive response was identified,
the "elbow flexion" was considered as the final positive response for successful
drug placement. The series of patients had difficulty for administering both
general and regional anesthesia and we considered them as complex scenarios. The
risk of the block failure was weighed heavily against the benefits of its
success. The described series includes patients who had successful outcomes in
the end and the techniques, merits, and risks are highlighted.
PMID- 26417147
TI - Anesthetic management of a patient with hypertrophic cardiomyopathy with atrial
flutter posted for percutaneous nephrolithotomy.
AB - Hypertrophic cardiomyopathy (HCM) is a most common genetic cardiovascular
disorder, characterized by asymmetric hypertrophy of the interventricular septum
that leads to intermittent obstruction of the left ventricular outflow tract
(LVOT). Clinical presentation ranges from absence of symptoms to sudden death in
the young and disability at any age. Although patients are asymptomatic in basal
conditions, but anesthesia and surgical stress can lead to exacerbation of the
LVOT obstruction and may complicate the perioperative course. Therefore, complete
understanding of the pathophysiology and anesthetic implications is needed for
the successful perioperative outcome. We describe the successful management of a
case of HCM with atrial flutter posted for percutaneous nephrolithotomy.
PMID- 26417148
TI - Hypopituitarism: A rare sequel of cerebral malaria - Presenting as delayed
awakening from general anesthesia.
AB - We report a case of delayed emergence from anesthesia in a 37-year-old male who
came for emergency laparoscopic appendicectomy. This patient is hailing from one
of the endemic zones of Malaria, Orissa State in India. Two months ago he had
cerebral malaria and was treated in our intensive care unit. After recovering
from cerebral malaria, he presented to us for acute abdomen, and he was taken for
emergency laparoscopic appendicectomy. He had delayed emergence of around 2 h to
extubate from the time of completion of surgery in spite of termination of
anesthetic agents. Further investigations showed to have decreased serum levels
of thyroid hormones and cortisol levels in the postoperative period. The
Physician promptly diagnosed the condition as hypopituitarism a known sequel of
cerebral malaria. The secondary thyroid insufficiency contributing to the delayed
emergence from anesthesia. We also review the pertinent literature related to
this rare sequelae of cerebral malaria and its perioperative implication to the
anesthesiologist.
PMID- 26417149
TI - Timely decision-making: How it saved us!!!
PMID- 26417151
TI - Front of Pack Labels Enhance Attention to Nutrition Information in Novel &
Commercial Brands.
AB - OBJECTIVES: 1) To assess whether Front-of-Pack (FOP) nutrition labels garner
attention more readily than more complete, mandated nutrition information (the
Nutrition Facts Panel (NFP), required in the US), and 2) To determine whether
label design characteristics, specifically, color coding and/or coding with
facial icons, increase attention to the FOP label. METHODS: In two experiments,
we tracked the allocation of attention while participants (n=125) viewed novel
and commercial packages with varied FOP designs using a change detection
methodology. RESULTS: We found empirical evidence that FOP labels are attended
more often, and earlier, than the currently mandated NFP, and that this benefit
is due both to its placement on the front of the package and to the design
characteristics of the FOP. Specifically, the use of color in FOPs increased
attention to the label, but there was no evidence that coding information via
facial icons impacted attention. CONCLUSIONS: Our work supports a growing body of
evidence supporting the use of FOP labels to attract attention to nutritional
information. Findings may be relevant to inform policy decisions on labeling
standards.
PMID- 26417150
TI - Polymorphism on Chromosome 9p21.3 Is Associated with Severity and Early-Onset CAD
in Type 2 Diabetic Tunisian Population.
AB - Multiple association studies found that the human 9p21.3 chromosome locus is a
risk factor for atherosclerosis. The purpose of this study was to investigate the
association of the severity and early-onset of coronary artery disease with
variant rs1333049 on chromosome 9p21.3 polymorphism and the impact of this
variant on cardiovascular risk factors in type 2 diabetic patients. The study
population consisted of a control CAD group (101 patients) and 273 consecutive
type 2 diabetic patients. Severity and extent of coronary atherosclerosis were
scored numerically using the Gensini scoring system. The diabetic population was
divided into three groups according to Gensini score: Group 1: no stenosis; Group
2: moderate CAD; Group 3, severe CAD. The homozygous CC genotype of rs1333049 was
significantly associated with CAD in Group 2 (OR: 1.36; p = 0.02) and Group 3
(OR: 5.77, p < 0.001) compared to Group 1 (OR: 0.18; p = 0.2) and control group
(OR: 0.22; p = 0.21). Among diabetic patients with early-onset CAD, CC genotype
carriers had significantly higher Gensini scores than non-CC genotype carriers
(49 +/- 21.3 versus 14.87 +/- 25.22; p < 0.001). The homozygous CC genotype of
rs1333049 confers a magnified risk of early-onset and severe CAD in type 2
diabetic Tunisian population.
PMID- 26417152
TI - Substance abuse and parenting among African American mothers of adolescents.
PMID- 26417154
TI - Can Establishment of Human Microbiome be Customized After Birth with Local
Traditions of First Feed and Intimate Kissing?
PMID- 26417153
TI - IL-4 Inhibits IL-1beta-Induced Depressive-Like Behavior and Central
Neurotransmitter Alterations.
AB - It has been known that activation of the central innate immune system or exposure
to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the
present study was to investigate the role of pro- and anti-inflammatory cytokines
in the modulation of depressive-like behaviors, the hormonal and neurotransmitter
systems in rats. We investigated whether centrally administered IL-1beta is
associated with activation of CNS inflammatory pathways and behavioral changes
and whether treatment with IL-4 could modulate IL-1beta-induced depressive-like
behaviors and central neurotransmitter systems. Infusion of IL-4 significantly
decreased IL-1beta-induced anhedonic responses and increased social exploration
and total activity. Treatment with IL-4 markedly blocked IL-1beta-induced
increase in PGE2 and CORT levels. Also, IL-4 reduced IL-1beta-induced 5-HT levels
by inhibiting tryptophan hydroxylase (TPH) mRNA and activating serotonin
transporter (SERT) in the hippocampus, and levels of NE were increased by
activating tyrosine hydroxylase (TH) mRNA expression. These results demonstrate
that IL-4 may locally contribute to the regulation of noradrenergic and
serotonergic neurotransmission and may inhibit IL-1beta-induced behavioral and
immunological changes. The present results suggest that IL-4 modulates IL-1beta
induced depressive behavior by inhibiting IL-1beta-induced central glial
activation and neurotransmitter alterations. IL-4 reduced central and systemic
mediatory inflammatory activation, as well as reversing the IL-1beta-induced
alterations in neurotransmitter levels. The present findings contribute a
biochemical pathway regulated by IL-4 that may have therapeutic utility for
treatment of IL-1beta-induced depressive behavior and neuroinflammation which
warrants further study.
PMID- 26417155
TI - Association of Serum Magnesium Deficiency with Insulin Resistance in Type 2
Diabetes Mellitus.
AB - BACKGROUND: Insulin resistance (IR) is the key pathophysiological defect that
leads to the development of type 2 diabetes mellitus. The purpose of this study
was to estimate serum magnesium level and insulin sensitivity indices among type
2 diabetes mellitus patients and to see an association between them. METHODS:
This study was carried out among 38 type 2 diabetic patients and forty age and
sex matched controls. Serum fasting glucose, magnesium, insulin, urea, and
creatinine levels were estimated. Insulin sensitivity indices, homeostasis model
assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity
check index (QUICKI) levels were calculated as per formulae. RESULTS: A highly
significant low serum magnesium level was found in diabetic subjects as compared
to the controls. Statistically significant high HOMA levels (>2.6) and low QUICKI
levels (<0.33) were found among the case group. An inverse, statistically
significant correlation was found between serum magnesium and fasting insulin
level. A highly statistically significant inverse correlation was found between
serum magnesium and HOMA level, and a positive correlation was found between
serum magnesium and QUICKI level, that is, serum magnesium level decreases with
increase in IR. A strong association was also found between fasting serum insulin
level and insulin sensitivity indices. CONCLUSION: This study showed a lower
serum magnesium level in diabetic patients compared to control. A strong
association was also found between serum magnesium level and insulin sensitivity
indices. For proper management of type 2 diabetes, it may, therefore, be
necessary to treat hypomagnesemia in these patients.
PMID- 26417156
TI - Epidermal Growth Factor Receptor Expression in Triple Negative and Nontriple
Negative Breast Carcinomas.
AB - INTRODUCTION: The panel of markers used for molecular classification include
estrogen receptors (ER), progesterone receptors (PR), human epidermal growth
factor receptor (HER)-2/neu, p53, Bcl-2 and basal markers like cytokeratin 5/6 or
epidermal growth factor receptor (EGFR). Among these, EGFR plays an important
role and is associated with bad prognosis. AIMS AND OBJECTIVES: To study EGFR
expression in triple negative breast carcinoma (TNBC) and non-TNBCs (NTNBCs).
MATERIALS AND METHODS: Fifty cases of breast carcinomas were classified and
graded according to World Health Organization and Nottingham modification of
Scarff-Bloom-Richardson (SBR) system, respectively. The age of the patients
ranged from 28 to 69 years. Histological features such as necrosis, pushing
borders, lymphocytic infiltrate and periductal elastosis were noted. The panel of
markers used in our study included ER, PR, HER-2/neu and EGFR. EGFR expression
was assessed based on membrane staining. Chi-square test was applied for
statistical analysis to compare EGFR expression with hormonal status and
prognostic factors. P < 0.05 was considered significant. RESULTS: The mean age
was 49.8 +/- 7.2 years. There were 44 (88%) infiltrating ductal carcinoma, 3 (6%)
medullary carcinoma and 3 (6%) mucinous carcinoma. EGFR expression was common in
young patients and was predominant in TNBC (89.47%), was also expressed in few
cases of NTNBC. There was a positive correlation of EGFR expression (P = 0.03491)
with a high grade. Medullary carcinomas were triple negative and strongly
expressed EGFR. EGFR expression was inversely associated with ER status and
showed strong association with necrosis and lymphocytic infiltrate, but not with
pushing border and periductal elastosis. CONCLUSION: EGFR is an important marker
to stratify patients with breast cancer according to molecular classification.
Its expression correlated positively with young age, higher SBR grade, necrosis,
lymphocytic infiltrate and inversely with hormonal receptor expression.
PMID- 26417157
TI - Clinicomycological Study of Dermatophytosis in South India.
AB - INTRODUCTION: Dermatophytic infections are commonly encountered a problem and
constitute more than 50% of cases in dermatology outpatient departments.
Diagnosis of these infections requires the proper use of laboratory methods.
OBJECTIVES: This study was conducted to know the etiology of dermatophytosis in
patients attending Tertiary Care Level Hospital in South India and to compare the
efficacy of Sabouraud's dextrose agar (SDA) with actidione and dermatophyte test
medium (DTM) in isolating and identifying dermatophytes. MATERIALS AND METHODS: A
total of 110 samples which included 101 skin samples and 9 hair samples from
clinically suspected dermatophytosis were collected. Direct microscopy by KOH and
culture on SDA with actidione and DTM were done. RESULTS: Of 110 samples
collected, 58.18% were KOH positive for fungal filaments and 56.36% were culture
positive for dermatophytes. More number of cases were observed between age groups
of 21-40 years. Males were more affected compared to females. Tinea corporis was
the common clinical presentation observed (40%). Trichophyton rubrum (58.06%) was
the predominant isolate recovered in all clinical presentations but Trichophyton
violaceum was the most common isolate in tinea capitis. All culture positives
were grown on both SDA with actidione and DTM. Appearance of growth was earlier
on DTM that is, within 10 days compared to SDA with actidione where growth
started appearing only after 10 days. This is statistically significant P <
0.0001 (chi(2) = 71.6). Species level identification on primary isolation was
possible when grown on SDA with actidione and it was not possible with the growth
on DTM on primary isolation. CONCLUSION: DTM is a good screening medium in
laboratory diagnosis of dermatophytosis when compared to SDA with actidione. But
DTM is inferior to SDA with actidione in identification of dermatophyte species.
PMID- 26417158
TI - Etiology of Pancytopenia: An Observation from a Referral Medical Institution of
Eastern Region of India.
AB - BACKGROUND: Pancytopenia is a relatively common hematological condition, the
etiological factors of which vary widely in different geographic location.
Determining the specific etiology is of immense importance for appropriate
management. AIMS AND OBJECTIVES: The present study was undertaken to delineate
etiological factors leading to pancytopenia in a Tertiary Care Hospital of West
Bengal from Eastern Region of India. MATERIALS AND METHODS: A prospective study
was conducted for a period of 2 years in which 248 patients were included. After
obtaining a relevant clinical history, physical examination was done followed by
complete blood count including peripheral blood smears examination, relevant
biochemical, and radiological investigations. Afterward, bone marrow aspiration
and biopsy were performed and microscopically examined. RESULTS: Among 248
patients studied, 156 (62.9%) were males and 92 (37.09%) were females. The mean
age of the patients was 33 years. Aplastic anemia was the most common cause of
pancytopenia that was observed in 83 cases (33.47%) followed by megaloblastic
anemia in 52 cases (20.97%), leishmaniasis in 34 patients (13.71%), hypersplenism
also in 34 patients (13.71%), and tuberculosis and other connective tissue
disorders in 18 cases (7.26%). The occurrence of aplastic anemia was
statistically significant in pediatric (<=15 years) age group. CONCLUSION:
Aplastic anemia was found to be the most common cause of pancytopenia in this
study, which is in contrast to studies conducted from other regions of India.
Delineation of etiologies of pancytopenia in various regions can help in defining
diagnostic and therapeutic strategies, which is expected to contribute toward the
better management of such patients.
PMID- 26417159
TI - Comparison Between Conventional and Automated Techniques for Blood Grouping and
Crossmatching: Experience from a Tertiary Care Centre.
AB - CONTEXT: The routine immunohematological tests can be performed by automated as
well as manual techniques. These techniques have advantages and disadvantages
inherent to them. AIMS: The present study aims to compare the results of manual
and automated techniques for blood grouping and crossmatching so as to validate
the automated system effectively. MATERIALS AND METHODS: A total of 1000 samples
were subjected to blood grouping by the conventional tube technique (CTT) and the
automated microplate LYRA system on Techno TwinStation. A total of 269 samples
(multitransfused patients and multigravida females) were compared for 927
crossmatches by the CTT in indirect antiglobulin phase against the column
agglutination technique (CAT) performed on Techno TwinStation. RESULTS: For blood
grouping, the study showed a concordance in results for 942/1000 samples (94.2%),
discordance for 4/1000 (0.4%) samples and uninterpretable result for 54/1000
samples (5.4%). On resolution, the uninterpretable results reduced to 49/1000
samples (4.9%) with 951/1000 samples (95.1%) showing concordant results. For
crossmatching, the automated CAT showed concordant results in 887/927 (95.6%) and
discordant results in 3/927 (0.32%) crossmatches as compared to the CTT. Total
37/927 (3.9%) crossmatches were not interpretable by the automated technique.
CONCLUSIONS: The automated system shows a high concordance of results with CTT
and hence can be brought into routine use. However, the high proportion of
uninterpretable results emphasizes on the fact that proper training and
standardization are needed prior to its use.
PMID- 26417160
TI - Prevalence of Mupirocin Resistance Among Staphylococci, its Clinical Significance
and Relationship to Clinical Use.
AB - INTRODUCTION: Mupirocin competitively inhibits bacterial isoleucyl transfer-RNA
synthetase and inhibit bacterial protein synthesis. Widespread usage and over the
counter availability of the drug has resulted in resistance among Staphylococcus
species. OBJECTIVES: This study aimed to determine the overall prevalence of
mupirocin resistance among staphylococci. Correlate clinical significance of
mupirocin resistance and its relationship to clinical use. METHODS: Consecutive,
nonrepetitive, clinical isolates of Staphylococcus aureus (n = 98), and coagulase
negative staphylococci (CoNS) (n = 45) from skin and soft-tissue infections
between January 2014 and June 2014 were studied. Antibiotic susceptibility
testing was done according to Clinical and Laboratory Standards Institute
guidelines. Low- and high-level mupirocin resistance was screened by using 5 ug
and 200 ug discs respectively and confirmed by agar dilution. Annual consumption
of mupirocin was studied and correlated with resistance. RESULTS: High-level
mupirocin resistance was found in 8.2% S. aureus and 15.6% of CoNS, while low
level mupirocin resistance was found in 17% S. aureus and 8.9% CoNS. High-level
mupirocin resistance was more common in methicillin-sensitive S. aureus isolates
when compared with methicillin-resistant S. aureus isolates (P < 0.05). Mupirocin
resistant S. epidermidis were associated with methicillin resistance and
constitutive clindamycin resistance. CONCLUSION: High prevalence of mupirocin
resistance was found in the present study. Increased prevalence of mupirocin
resistance among community-acquired staphylococci demands the judicious use of
the drug in the community.
PMID- 26417161
TI - Vancomycin-resistance Enterococcal Colonization in Hospitalized Patients in
Relation to Antibiotic Usage in a Tertiary Care Hospital of North India.
AB - BACKGROUND: Alarming rise of vancomycin-resistant enterococci (VRE) is a global
cause of concern. Several factors have been held responsible for such rise, of
which antibiotic usage is a prominent one. OBJECTIVE: This study was undertaken
to determine the intestinal VRE colonization rate amongst hospitalized patients
in relation to use of various antibiotics in the Intensive Care Unit (ICU) of a
tertiary care university hospital, India. MATERIALS AND METHODS: Stool samples
were collected weekly from all the patients in the adult ICU for a period of 6
months and processed for isolation and phenotypic and genotypic characterization
of VRE isolates. Patient and treatment details were noted and cases (those with
VRE in stool) and controls (those without VRE in stool) were compared
statistically. Further, a multivariate analysis was done to identify those
antibiotics as independent risk factors for VRE colonization. RESULTS: VRE
colonization was found in 34.56% (28/81) of the patients studied, with the
majority 75% (21/28) carrying the vanA gene. The cases had significantly more (P
< 0.05) duration of hospital stay and antibiotic exposure. Intake of
metronidazole, vancomycin, and piperacillin-tazobactam were identified as
significant risk factors both in univariate and multivariate analysis.
CONCLUSION: A potential reservoir of VRE was thus revealed even in low VRE
prevalence setting. Based on this high colonization status, restriction of
empirical antibiotic use, reviewing of the ongoing antibiotic policy, and active
VRE surveillance as an integral part of infection control strategy were
suggested.
PMID- 26417162
TI - Relationship Between Insulin Resistance and Mean Platelet Volume in Gestational
Diabetes Mellitus.
AB - OBJECTIVES: A few studies have investigated the relationship between mean
platelet volume (MPV) and gestational diabetes mellitus (GDM), and in these
studies the relationship between MPV and insulin resistance has not been
analyzed. Our aim in this study was to compare MPV values of the pregnant women
with or without GDM and evaluate the relationship between MPV and homeostasis
model assessment insulin resistance index (HOMA-IR) in pregnant women. MATERIALS
AND METHODS: One hundred and fourteen with GDM measurements being obtained before
any dietary advice or therapy with insulin or hypoglycemic agents were given, and
76 with healthy pregnant women were included the study. RESULTS: In the group
with GDM, MPV value was found to be significantly higher than that of the control
group (10.2 fl [8.0-12.2] vs. 9.9 fl [5.81-10.9], P = 0.004). HOMA-IR value was
detected to be significantly higher in the group with GDM (2.46 [1.5-5.88] vs.
1.30 [0.17-2.92], P < 0.001). A positive correlation between MPV and HOMA-IR was
found (r = 0.30, P = 0.002). CONCLUSION: We have shown that MPV was significantly
elevated in GDM patients when compared to healthy pregnant women. Furthermore, we
found that there was a positive correlation between MPV and HOMA-IR.
PMID- 26417163
TI - Febrile Neutropenia in Hematological Malignancies: Clinical and Microbiological
Profile and Outcome in High Risk Patients.
AB - BACKGROUND AND OBJECTIVES: Febrile neutropenia (FN) is considered a medical
emergency. Patients with hematological malignancies (HM) commonly experience FN.
Broad spectrum antibiotics have to be started empirically to prevent
complications. This study depicts the clinical profile, microbiological profile,
antibiotic sensitivity pattern, and outcome in high risk HM. MATERIALS AND
METHODS: In this prospective study, 72 patients with hematologic malignancies,
diagnosed and treated for 108 high risk febrile neutropenic episodes from August
2011 to January 2013 at a Regional Cancer Center, in South India were analyzed.
Cefoperazone-sulbactum was used as a first-line empiric antibiotic. RESULTS:
Majority of the patients with FN episodes had acute myeloid leukemia. Overall
culture positivity was 29.62%. The most common organisms isolated were Gram
negative bacilli (63.64%), with Escherichia coli being the most frequent
pathogen. All Gram-negative organisms were sensitive to imipenem, whereas
sensitivity pattern to other antibiotics were as follows: 85.71%, 78.26%, 69.52%,
63.64%, 41.66% and 47.05% for pipercillin-tazoactum, meropenem, cefoperazone
sulbactum, amikacin, ceftazidime, ciprofloxacin respectively. Overall mortality
was 13.5%. Most of the patients responded to empiric antibiotic cefoperazone
sulbactum. CONCLUSIONS: In the hematologic malignancies particularly in acute
leukemia, there is high risk of developing FN. Empiric therapy with cefoperazone
sulbactum as a first line leads to satisfactory outcome in high risk FN and
therapy should be tailored to the most appropriate antibiotics according to the
bacterial culture results.
PMID- 26417165
TI - Achromobacter Xylosoxidans Bloodstream Infection in Elderly Patient with
Hepatocellular Carcinoma: Case Report and Review of Literature.
AB - Achromobacter xylosoxidansis a nonfermentative Gram-negative organism, known to
cause opportunistic infection in humans. We report a case of septicemia in a 76
year-old male patient with underlying hepatocellular carcinoma due to A.
xylosoxidans, which showed a different antimicrobial susceptibility pattern from
what is usually reported. From aerobic blood culture of the patient, A.
xylosoxidans was isolated which was found to be sensitive to amoxicillin
clavulanic acid, piperacillin-tazobactam, ceftazidime, cefoperazone-sulbactam,
meropenem, minocycline, tigecycline, and trimethoprim/sulfamethoxazole. The
patient recovered with amoxicillin-clavulanic acid treatment, which was given
empirically to the patient. The present case highlights the possible role of
amoxicillin-clavulanic acid for treatment of bloodstream infection with A.
xylosoxidans.
PMID- 26417164
TI - Renal Abscess Caused by Salmonella Typhi.
AB - Salmonella typhi is a true pathogen, which is capable of causing both intestinal
and extraintestinal infections. Unusual presentations of Salmonella should always
be kept in mind as this organism can cause disease in almost any organ of the
body. S. typhi has been reported to cause the life-threatening infections such as
meningitis, endocarditis, myocarditis, empyema, and hepatic abscess. Renal
involvement by S. typhi is a relatively rare presentation. We report a case of
renal abscess caused by S. typhi in an afebrile, 10-year-old child who did not
have any clinical history of enteric fever. To our knowledge, this is the first
reported case of isolation of S. typhi from the renal abscess, and interestingly
this isolate was found to be resistant to quinolones.
PMID- 26417166
TI - Transfusion-acquired Hemoglobinopathies: A Report of Two Cases.
AB - Transfusion-acquired hemoglobinopathy occurs when a carrier of hemoglobinopathy
with no significant abnormalities donates blood, and the blood is transfused to a
recipient. This process can lead to spurious results in the recipient without any
clinical abnormality or infrequently can result in disastrous situations. The
incidental finding of such posttransfusion related abnormal peaks in hemoglobin
high-performance liquid chromatography (Hb HPLC) may cause diagnostic dilemmas
and result in unnecessary laboratory testing. Here, we report two such cases of
transfusion-acquired hemoglobinopathies, which were subsequently resolved by the
abnormally low percentage of the Hb variants, transient nature of the peaks, and
parental Hb HPLC.
PMID- 26417167
TI - Perinatal Autopsy Findings in a Case of De Novo Hypohidrotic Ectodermal
Dysplasia.
AB - Ectodermal dysplasia are group of inherited disorders involving the developmental
defects of ectodermal structures like hair, teeth, nails, sweat glands, and
others. X-linked recessive inheritance is most common. Here we describe perinatal
autopsy findings in a case of de novo ectodermal dysplasia in a female fetus. To
the best of our knowledge, this is the first fetal autopsy description in a case
of ectodermal dysplasia.
PMID- 26417168
TI - Concomitant Infections of Influenza A H1N1 and Disseminated Cryptococcosis in an
HIV Seropositive Patient.
AB - Respiratory viral infections, especially influenza have a potential to form a
fatal association with cryptococcosis in the setting of compromised immunity.
Considering the lethality of these two infections, we report an unusual case of
dual infection of pandemic influenza A H1N1 and disseminated cryptococcosis in an
HIV seropositive individual.
PMID- 26417170
TI - ISMP Survey Reveals User Issues With Carpuject Prefilled Syringes.
AB - An ISMP survey finds problems involving proper use of Carpuject prefilled
syringes.
PMID- 26417169
TI - Cyclosporine Drug Levels: Comparison of the Architect 1000i with the Siemens
Dimension RXL System.
PMID- 26417171
TI - ACO Final Rule Slights Pharmacy: No "Give" on Drug Pricing, Cost Shifting, and
Other Concerns.
AB - The Centers for Medicare and Medicaid Service's final ACO rule offers little for
pharmacists.
PMID- 26417173
TI - Pharmaceutical Approval Update.
AB - Sacubitril/valsartan (Entresto) for chronic heart failure; brexpiprazole
(Rexulti) for major depressive disorder and schizophrenia; and
lumacaftor/ivacaftor (Orkambi) for cystic fibrosis involving specific CFTR
mutations.
PMID- 26417174
TI - Two Draft FDA Guidance Documents Stir Controversy: Hospital and 503B Pharmacy
Repackaging and Compounding Are at Issue.
AB - The Food and Drug Administration hopes to close gaps in laws related to
repackaging of pharmaceuticals or biologics by hospital pharmacies and bulk
compounding facilities.
PMID- 26417175
TI - Caring for Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Patients:
Implications for Pharmacy.
AB - This article explores the basis of glucose-6-phosphate dehydrogenase deficiency
and defines the role that health care informatics can play in optimal treatment.
PMID- 26417176
TI - The Affordable Care Act, Five Years Later: Policies, Progress, and Politics.
AB - The Affordable Care Act, which recently survived a second Supreme Court
challenge, has increased health care access without causing most of the
disruption critics feared.
PMID- 26417177
TI - Professional Roles Evolve With Changing Landscape of Legal Risk.
AB - Opioid-use monitoring, medication-error prevention, and counseling/duty-to-warn
issues illustrate new or emerging legal risks for pharmacists as their roles
expand.
PMID- 26417178
TI - Researchers Expand Focus on Progressive Forms Of Multiple Sclerosis: Efforts to
Pinpoint the Beginning of Disease May Yield Clues to Treatment.
AB - With disease-modifying treatments available for relapsing-remitting multiple
sclerosis (MS), the quest for therapies for progressive MS has become a key focus
of research.
PMID- 26417180
TI - European Society of Medical Oncology: 17th World Congress on Gastrointestinal
Cancer.
AB - We review sessions on metastatic colorectal cancer and hepatocellular carcinoma.
PMID- 26417181
TI - Multiple Sclerosis: Progress, but No Cure.
AB - Agents are approved to treat exacerbations and symptoms and as disease-modifying
therapy. Most therapies in the works would address relapsing forms of the
disease.
PMID- 26417179
TI - Part 2: Introduction to the Pharmacotherapy of Parkinson's Disease, With a Focus
on the Use of Dopaminergic Agents.
AB - This second of five articles reviews Parkinson's disease pharmacotherapy,
focusing on dopaminergic agents such as levodopa/carbidopa and dopamine receptor
agonists.
PMID- 26417182
TI - Atherosclerotic Plaque Composition Is Still an Almost Unrecognized Factor of Risk
Stratification in Patients with Carotid Artery Disease.
PMID- 26417184
TI - Assessment of Carotid Artery Stenosis and the Use of Statins.
AB - General thinking has previously centered on managing carotid artery stenosis
(CAS) by carotid endarterectomy and subsequently, stenting for higher risk
patients. However for CAS and other forms of vascular disease, especially when
asymptomatic, there is new emphasis on defining underlying mechanisms. Knowledge
of these mechanisms can lead to medical treatments that result in possible
atherosclerotic plaque stabilization, and even plaque regression, including in
the patient with CAS. For now, the key medication class for a medical approach
are the statins. Their use is supported by good cardiovascular clinical trial
evidence including some directed carotid artery studies, especially with a
demonstrated decrease in carotid intima-media thickness. Procedural controversy
still exists but the current era in medicine offers significant support for
medical management of asymptomatic CAS while techniques to recognize the
vulnerable plaque evolve. If CAS converts to a symptomatic status, early referral
for endarterectomy or stenting is indicated.
PMID- 26417185
TI - Multimodality Imaging of Carotid Stenosis.
AB - Four diagnostic modalities are used to image the following internal carotid
artery: digital subtraction angiography (DSA), duplex ultrasound (DUS), computed
tomography angiography (CTA), and magnetic resonance angiography (MRA). The aim
of this article is to describe the potentials of these techniques and to discuss
their advantages and disadvantages. Invasive DSA is still considered the gold
standard and is an indivisible part of the carotid stenting procedure. DUS is an
inexpensive but operator-dependent tool with limited visibility of the carotid
artery course. Conversely, CTA and MRA allow assessment of the carotid artery
from the aortic arch to intracranial parts. The disadvantages of CTA are
radiation and iodine contrast medium administration. MRA is without radiation but
contrast-enhanced MRA is more accurate than noncontrast MRA. The choice of
methods depends on the clinical indications and the availability of methods in
individual centers. However, the general approach to patient with suspected
carotid artery stenosis is to first perform DUS and then other noninvasive
methods such as CTA, MRA, or transcranial Doppler US.
PMID- 26417186
TI - Utilization of Intravascular Ultrasound during Carotid Artery Stenting.
AB - For patients at high risk for surgery, carotid artery stenting (CAS) is a viable
alternative to help reduce risk of stroke for patients with high-grade carotid
artery stenosis; however, a higher incidence of perioperative stroke has been
observed in patients undergoing stenting compared to those undergoing open
surgery. Intravascular ultrasound (IVUS) is commonly used during coronary artery
procedures to help evaluate lesions and to guide stent placement. Multiple groups
have sought to determine whether IVUS could also be used during CAS. While IVUS
has been shown to be both feasible and safe during CAS, there is limited evidence
that demonstrates direct improvement in procedural outcomes. Further studies
focusing on clinical outcomes should be conducted in order to justify routine use
of this technology during CAS.
PMID- 26417183
TI - Pathophysiology and Medical Treatment of Carotid Artery Stenosis.
AB - Stroke is the third leading cause of mortality. Approximately 80 to 85% strokes
are ischemic due to carotid artery stenosis (CAS). The prevalence of significant
CAS is 7% in women and 9% in men. Severe asymptomatic CAS varies from 0 to 3.1%.
Prevalence of symptomatic CAS is high in patients with peripheral arterial
disease. CAS is due to atherosclerosis, the major risk factors for which include
dyslipidemia, hypertension, diabetes, obesity, cigarette smoking, advanced
glycation end products (AGEs) and its receptors (RAGE, soluble RAGE [sRAGE]),
lack of exercise and C-reactive protein (CRP). This article discusses the basic
mechanism of atherosclerosis and the mechanisms by which these risk factors
induce atherosclerosis. The role of AGEs and its receptors in the development and
progression of CAS has been discussed in detail. Lifestyle changes and medical
treatment of CAS such as lifestyle changes, lipid-lowering agents,
antihypertensive agents, antidiabetic drugs, anti-AGE therapy, measures to
elevate soluble receptors of AGE (sRAGE, esRAGE). CRP-lowering agents have been
discussed in detail. The drugs especially lipid-lowering agents, and
antihypertensive and antidiabetic drugs suppress, regress, and slow the
progression of CAS. The possible role of lowering the levels of AGEs and raising
the levels of sRAGE in the treatment of CAS has been proposed. Lifestyle changes
besides medical treatment have been stressed. Lifestyle changes and medical
treatment not only would slow the progression of CAS but would also regress the
CAS.
PMID- 26417187
TI - Ascending Aortic Proaneurysmal Genetic Mutations with Antiatherogenic Effects.
AB - Thoracic aortic aneurysms are common and are associated with a high morbidity and
mortality. Despite this lethal diagnosis, there is an increasing body of evidence
to suggest that the diagnosis of an aneurysm, specifically in the ascending
thoracic aorta, may significantly reduce the risk of developing systemic
atherosclerosis. Clinical observations in the operating room have shown pristine
blood vessels in patients undergoing surgery for thoracic aortic aneurysms. There
is now evidence that both the carotid intima-media thickness and arterial
calcification, which are early and late signs of atherosclerosis respectively,
are decreased in those with thoracic aortic aneurysms. These clinical studies are
supported by molecular, genetic, and pharmacological evidence. Two principle
mechanisms have been identified to explain the relationship of a proaneurysmal
state conferring protection from atherosclerosis. These include an excess
proteolytic balance of matrix metalloproteinase activity, leading to
fragmentation of elastic lamellae and disordered collagen deposition. In
addition, transforming growth factor beta modulates vascular smooth muscle cells,
extracellular matrix, and leukocytes. This confers protection from the initial
plaque formation and, later provides stability to the plaque possibly through
alteration of the types I and II transforming growth factor beta receptor ratio.
Furthermore, studies are now beginning to establish an important role for statins
and estradiol in modulating these complex pathways. In the future, as our
understanding of these complex mechanisms underlying aneurysmal protection
against atherosclerosis increases, corresponding therapies may be developed to
offer protection from atherosclerosis.
PMID- 26417188
TI - Intravascular Near-Infrared Spectroscopy: A Possible Tool for Optimizing the
Management of Carotid Artery Disease.
AB - Stroke is the second most common cause of morbidity and mortality in the Western
nations. It is estimated that approximately one-fifth of all strokes or transient
ischemic attacks are caused by carotid artery disease. Thus, treatment of carotid
artery disease as a mean of stroke prevention is extremely important. Since the
introduction of carotid endarterectomy, debate has persisted over the treatment
strategy for carotid artery disease. Current recommendations have many potential
flaws because they are often based on older trials performed before the
introduction of modern pharmacotherapy and are mostly based on the angiographic
degree of stenosis, without an emphasis on the pathophysiology of the disease.
Most carotid events are caused by rupture or distal embolization of the content
of an unstable atherosclerotic plaque with a large lipid pool. Thus, it is
plausible that the information regarding the composition of the atherosclerotic
plaque could play an important role in deciding on a treatment strategy. In this
review article, we provide information about near-infrared spectroscopy, a new
invasive imaging modality, which seems to be capable of providing such
information.
PMID- 26417189
TI - Carotid Artery Stenting-Historical Context, Trends, and Innovations.
AB - Surgical carotid endarterectomy (CEA) has been proven effective in both primary
and secondary stroke prevention and, until recently, has been considered the
standard treatment approach for patients with severe carotid artery disease.
Because of its technical limitations and less favorable outcomes, carotid artery
stenting (CAS) has been offered preferably to patients considered to be too
comorbid to undergo surgical treatment. However, CAS has evolved over time into a
reliable method and is currently considered an alternative to CEA. The aim of
this review was to discuss the historical aspects, trends, and innovations in
CAS.
PMID- 26417190
TI - Predicting Hemodynamic Changes of Cerebral Blood Flow during Temporal Carotid
Occlusion: A Review of Current Knowledge with Implication for Carotid Artery
Stenting.
AB - Carotid artery disease (CAD) plays an important role in the stroke development
and its prevalence increases with aging of the population. Its wide variability
of clinical manifestation ranges from incidental asymptomatic finding to
devastating or fatal stroke, although cerebral collateral circulation is
considered one of the major modifying factors. Over time, carotid artery stenting
(CAS) has evolved into a reputable method for the treatment of patients with
severe CAD. With expanding use of proximal protection systems resembling surgical
clamp, there is an increasing demand to understand collateral cerebral
circulation to protect patients from periprocedural hypoperfusion, which
increases the risk of cerebral events. Transcranial Doppler ultrasound (TCD) is a
useful tool allowing monitoring in real time during procedure patients cerebral
hemodynamic status providing the operator with valuable information. Its role in
predicting periprocedural hypoperfusion is, however, less well established. In
this article, we discuss the role of cerebral collateral circulation, summarize
the current knowledge regarding its evaluation with TCD and suggest future
implications for CAS.
PMID- 26417191
TI - Comparative Review of the Treatment Methodologies of Carotid Stenosis.
AB - The treatment of carotid stenosis entails three methodologies, namely, medical
management, carotid angioplasty and stenting (CAS), as well as carotid
endarterectomy (CEA). The North American Symptomatic Carotid Endarterectomy Trial
(NASCET) and European Carotid Surgery Trial (ECST) have shown that symptomatic
carotid stenosis greater than 70% is best treated with CEA. In asymptomatic
patients with carotid stenosis greater than 60%, CEA was more beneficial than
treatment with aspirin alone according to the Asymptomatic Carotid
Atherosclerosis (ACAS) and Asymptomatic Carotid Stenosis Trial (ACST) trials.
When CAS is compared with CEA, the CREST resulted in similar rates of ipsilateral
stroke and death rates regardless of symptoms. However, CAS not only increased
adverse effects in women, it also amplified stroke rates and death in elderly
patients compared with CEA. CAS can maximize its utility in treating focal
restenosis after CEA and patients with overwhelming cardiac risk or prior neck
irradiation. When performing CEA, using a patch was equated to a more durable
result than primary closure, whereas eversion technique is a new methodology
deserving a spotlight. Comparing the three major treatment strategies of carotid
stenosis has intrinsic drawbacks, as most trials are outdated and they vary in
their premises, definitions, and study designs. With the newly codified best
medical management including antiplatelet therapies with aspirin and clopidogrel,
statin, antihypertensive agents, strict diabetes control, smoking cessation, and
life style change, the current trials may demonstrate that asymptomatic carotid
stenosis is best treated with best medical therapy. The ongoing trials will
illuminate and reshape the treatment paradigm for symptomatic and asymptomatic
carotid stenosis.
PMID- 26417193
TI - The Paramount Role of the Anterior Communicating Artery in the Collateral
Cerebral Circulation.
AB - Clinical manifestation of carotid occlusive disease is largely dependent on the
severity of stenosis and the capability of collateral circulation. However, due
to the complexity and difficulty in evaluation, cerebral collateral circulation
has, so far, remained underappreciated. We report a patient with advanced
extracranial arterial disease (including the right subclavian steal, occlusion of
the right external carotid artery, and severe stenosis of the left vertebral
artery), who underwent transient right internal carotid artery occlusion during
carotid intervention. Throughout the occlusion, the flow into the right
hemisphere (monitored by transcranial Doppler ultrasound in the right middle
cerebral artery) was sufficient despite almost totally dependent on the anterior
communicating artery, which highlights its role as the most potent collateral
pathway.
PMID- 26417192
TI - Carotid Endarterectomy: Current Concepts and Practice Patterns.
AB - Background Stroke is the number one cause of disability and third leading cause
of death among adults in the United States. A major cause of stroke is carotid
artery stenosis (CAS) caused by atherosclerotic plaques. Randomized trials have
varying results regarding the equivalence and perioperative complication rates of
stents versus carotid endarterectomy (CEA) in the management of CAS. Objectives
We review the evidence for the current management of CAS and describe the current
concepts and practice patterns of CEA. Methods A literature search was conducted
using PubMed to identify relevant studies regarding CEA and stenting for the
management of CAS. Results The introduction of CAS has led to a decrease in the
percentage of CEA and an increase in the number of CAS procedures performed in
the context of all revascularization procedures. However, the efficacy of stents
in patients with symptomatic CAS remains unclear because of varying results among
randomized trials, but the perioperative complication rates exceed those found
after CEA. Conclusions Vascular surgeons are uniquely positioned to treat carotid
artery disease through medical therapy, CEA, and stenting. Although data from
randomized trials differ, it is important for surgeons to make clinical decisions
based on the patient. We believe that CAS can be adopted with low complication
rate in a selected subgroup of patients, but CEA should remain the standard of
care. This current evidence should be incorporated into practice of the modern
vascular surgeon.
PMID- 26417194
TI - Fibromuscular Dysplasia of Renal and Carotid Arteries.
AB - We report here two cases of fibromuscular dysplasia (FMD). The first case
describes an asymptomatic 75-year-old man with FMD of the right internal carotid
artery. The second case reports a 17-year-old man who presented with arterial
hypertension caused by FMD of the left renal artery and was subsequently
successfully treated by angioplasty. FMD is a rare nonatherosclerotic,
noninflammatory angiopathy, which can involve almost every arterial vascular bed.
It is a less common cause of stenosis of renal and carotid arteries. FMD can
present with arterial hypertension when it involves renal arteries or with
ischemic stroke or transient ischemic attack when the disease affects the carotid
or vertebral arteries. Many cases are asymptomatic and may be discovered
incidentally. Percutaneous transluminal angioplasty should be used in patients
with a stenosis of the renal artery causing arterial hypertension. On the
contrary, conservative therapy should be chosen in patients with asymptomatic and
extensive lesions of the carotid arteries.
PMID- 26417195
TI - Rare Case of Takayasu Arteritis with Concurrent Aneurysmal Dilation and Stenosis.
AB - Takayasu arteritis is a rare, chronic large vessel vasculitis that primarily
affects women aged 10 to 40 years of Asian descent. The inflammatory processes of
the disease can result in stenosis and/or occlusion of the aorta and its
branches, causing a wide range of symptoms. Rarely, damage of the elastic lamina
or muscular media can cause aneurysmal dilation of the affected vessel. Diagnosis
is based on the clinical presentation, laboratory proof of inflammation, and
imaging finding of wall thickening in the acute phase and later arterial stenosis
or occlusion. Management includes disease control with immunosuppression and some
patients might require revascularization. Here, we present a rare case of
Takayasu arteritis with both right common carotid artery aneurysmal dilation and
stenosis at a conforming site. Although aneurysmal dilation has been sparsely
reported in the Takayasu arteritis literature, our case may represent the
distinct finding of concomitant dilation and stenosis in this disease.
PMID- 26417197
TI - Expression Divergence of Duplicate Genes in the Protein Kinase Superfamily in
Pacific Oyster.
AB - Gene duplication has been proposed to serve as the engine of evolutionary
innovation. It is well recognized that eukaryotic genomes contain a large number
of duplicated genes that evolve new functions or expression patterns. However, in
mollusks, the evolutionary mechanisms underlying the divergence and the
functional maintenance of duplicate genes remain little understood. In the
present study, we performed a comprehensive analysis of duplicate genes in the
protein kinase superfamily using whole genome and transcriptome data for the
Pacific oyster. A total of 64 duplicated gene pairs were identified based on a
phylogenetic approach and the reciprocal best BLAST method. By analyzing gene
expression from RNA-seq data from 69 different developmental and stimuli-induced
conditions (nine tissues, 38 developmental stages, eight dry treatments, seven
heat treatments, and seven salty treatments), we found that expression patterns
were significantly correlated for a number of duplicate gene pairs, suggesting
the conservation of regulatory mechanisms following divergence. Our analysis also
identified a subset of duplicate gene pairs with very high expression divergence,
indicating that these gene pairs may have been subjected to transcriptional
subfunctionalization or neofunctionalization after the initial duplication
events. Further analysis revealed a significant correlation between expression
and sequence divergence (as revealed by synonymous or nonsynonymous substitution
rates) under certain conditions. Taken together, these results provide evidence
for duplicate gene sequence and expression divergence in the Pacific oyster,
accompanying its adaptation to harsh environments. Our results provide new
insights into the evolution of duplicate genes and their expression levels in the
Pacific oyster.
PMID- 26417196
TI - Assessing Adolescent Substance Abuse Programs with Updated Quality Indicators:
The Development of a Consumer Guide for Adolescent Treatment.
AB - When adolescent substance abuse requires treatment, few parents know which
treatment features are important and which treatment programs are effective.
There are few resources to help them select appropriate care. We describe early
work on an evaluation method and comparative treatment guide for parents based
upon the premise that the quality of a program and its potential effectiveness is
a function of the number and frequency of evidence-based treatment practices
(EBPs) delivered. Thus, we describe the development of and measurement approach
for a set of EBPs toward the goal of developing a Consumer Guide to Adolescent
Substance Abuse Treatment.
PMID- 26417198
TI - Alview: Portable Software for Viewing Sequence Reads in BAM Formatted Files.
AB - The name Alview is a contraction of the term Alignment Viewer. Alview is a
compiled to native architecture software tool for visualizing the alignment of
sequencing data. Inputs are files of short-read sequences aligned to a reference
genome in the SAM/BAM format and files containing reference genome data. Outputs
are visualizations of these aligned short reads. Alview is written in portable C
with optional graphical user interface (GUI) code written in C, C++, and
Objective-C. The application can run in three different ways: as a web server, as
a command line tool, or as a native, GUI program. Alview is compatible with
Microsoft Windows, Linux, and Apple OS X. It is available as a web demo at
https://cgwb.nci.nih.gov/cgi-bin/alview. The source code and Windows/Mac/Linux
executables are available via https://github.com/NCIP/alview.
PMID- 26417199
TI - Directed Differentiation of Pluripotent Stem Cells into Kidney.
AB - Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced
pluripotent stem cells (iPSCs), represent an ideal substrate for regenerating
kidney cells and tissue lost through injury and disease. Recent studies have
demonstrated the ability to differentiate PSCs into populations of nephron
progenitor cells that can organize into kidney epithelial structures in three
dimensional contexts. While these findings are highly encouraging, further
studies need to be performed to improve the efficiency and specificity of kidney
differentiation. The identification of specific markers of the differentiation
process is critical to the development of protocols that effectively recapitulate
nephrogenesis in vitro. In this review, we summarize the current studies
describing the differentiation of ESCs and iPSCs into cells of the kidney
lineage. We also present an analysis of the markers relevant to the stages of
kidney development and differentiation and propose a new roadmap for the directed
differentiation of PSCs into nephron progenitor cells of the metanephric
mesenchyme.
PMID- 26417201
TI - Molecular Dynamics Approach in the Comparison of Wild-Type and Mutant Paraoxonase
1 Apoenzyme Form.
AB - There is some evidence linking the mammalian paraoxonase-1 (PON1) loops (L1 and
L2) to an increased flexibility and reactivity of its active site with potential
substrates. The aim of this work is to study the structural, dynamical, and
functional effects of the most flexible regions close to the active site and to
determine the impact of mutations on the protein. For both models, wild-type
(PON1wild) and PON1 mutant (PON1mut) models, the L1 loop and Q/R and L/M
mutations were constructed using MODELLER software. Molecular dynamics
simulations of 20 ns at 300 K on fully modeled PON1wild and PON1mut apoenzyme
have been done. Detailed analyses of the root-mean-square deviation and
fluctuations, H-bonding pattern, and torsion angles have been performed. The
PON1wild results were then compared with those obtained for the PON1mut. Our
results show that the active site in the wild-type structure is characterized by
two distinct movements of opened and closed conformations of the L1 and L2 loops.
The alternating and repetitive movement of loops at specific times is consistent
with the presence of 11 defined hydrogen bonds. In the PON1mut, these open-closed
movements are therefore totally influenced and repressed by the Q/R and L/M
mutations. In fact, these mutations seem to impact the PON1mut active site by
directly reducing the catalytic core flexibility, while maintaining a significant
mobility of the switch regions delineated by the loops surrounding the active
site. The impact of the studied mutations on structure and dynamics proprieties
of the protein may subsequently contribute to the loss of both flexibility and
activity of the PON1 enzyme.
PMID- 26417200
TI - Biomarkers for Sepsis: What Is and What Might Be?
AB - Every year numerous individuals develop the morbid condition of sepsis.
Therefore, novel biomarkers that might better inform clinicians treating such
patients are sorely needed. Difficulty in identifying such markers is in part due
to the complex heterogeneity of sepsis, resulting from the broad and vague
definition of this state/condition based on numerous possible clinical signs and
symptoms as well as an incomplete understanding of the underlying pathobiology of
this complex condition. This review considers some of the attempts that have been
made so far, looking at both the pro- and anti-inflammatory response to sepsis,
as well as genomic analysis, as sources of potential biomarkers. Irrespective,
for functional biomarker(s) of sepsis to successfully translate from the
laboratory to a clinical setting, the biomarker must be target specific and
sensitive as well as easy to implement/interpret, and be cost effective, such
that they can be utilized routinely in patient diagnosis and treatment.
PMID- 26417203
TI - Everolimus in the Treatment of Metastatic Breast Cancer.
AB - The discovery of the mammalian target of rapamycin (mTOR) molecular pathway has
brought insight into its vital role in breast cancer pathogenesis. Several
clinical trials have shown that the mTOR inhibitor everolimus could improve
patient outcomes in several subtypes of breast cancer, including hormone receptor
positive, human epidermal growth factor receptor-negative metastatic disease that
has progressed after prior endocrine therapy. This review summarizes findings
from clinical trials that have demonstrated the benefit of everolimus in
metastatic breast cancer and highlights some new research directions utilizing
everolimus.
PMID- 26417202
TI - Impact of Chronic Pain on Treatment Prognosis for Patients with Opioid Use
Disorder: A Systematic Review and Meta-analysis.
AB - BACKGROUND: While a number of pharmacological interventions exist for the
treatment of opioid use disorder, evidence evaluating the effect of pain on
substance use behavior, attrition rate, and physical or mental health among these
therapies has not been well established. We aim to evaluate these effects using
evidence gathered from a systematic review of studies evaluating chronic non
cancer pain (CNCP) in patients with opioid use disorder. METHODS: We searched the
Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Database of
Systematic Reviews, ProQuest Dissertations and theses Database, Cochrane Central
Register of Controlled Trials, World Health Organization International Clinical
Trials Registry Platform Search Portal, and National Institutes for Health
Clinical Trials Registry databases to identify articles evaluating the impact of
pain on addiction treatment outcomes for patients maintained on opioid agonist
therapy. RESULTS: Upon screening 3,540 articles, 14 studies with a combined
sample of 3,128 patients fulfilled the review inclusion criteria. Results from
the meta-analysis suggest that pain has no effect on illicit opioid consumption
[pooled odds ratio (pOR): 0.70, 95%CI 0.41-1.17; I (2) = 0.0] but a protective
effect for reducing illicit non-opioid substance use (pOR: 0.57, 95%CI 0.41-0.79;
I (2) = 0.0). Studies evaluating illicit opioid consumption using other measures
demonstrate pain to increase the risk for opioid abuse. Pain is significantly
associated with the presence of psychiatric disorders (pOR: 2.18; 95%CI 1.6, 2.9;
I (2) = 0.0%). CONCLUSION: CNCP may increase risk for continued opioid abuse and
poor psychiatric functioning. Qualitative synthesis of the findings suggests that
major methodological differences in the design and measurement of pain and
treatment response outcomes are likely impacting the effect estimates.
PMID- 26417204
TI - Subverting Subversion: A Review on the Breast Cancer Microenvironment and
Therapeutic Opportunities.
AB - This review combines the recent research on the subject of tumor immunology and
methods of correcting the immune system's reaction to the tumor microenvironment
while impeding the survival and growth of tumor cells, with a focus on breast
cancer. Induction of hypoxia-inducible genes in the microenvironment leads to
lowering of its pH. This impedes the adaptive immune response and acts to recruit
cells of the immune system, which suppress the immune response. Regulatory T
cells (Tregs), myeloid-derived suppressor cells (MDSCs), and their derivatives
coordinate an anti-autoimmunity response and a healing response in concert with
tumor-secreted cytokines, enzymes, and antigens. Together, they suppress a proper
immune reaction to tumor cells and promote cellular reproduction (Fig. 1). In
addition, the hypoxia-inducible response and components of the tumor
microenvironment such as cancer-associated fibroblasts (CAFs) also create an
ideal environment for tumor growth and metastasis via neoangiogenesis and
increased motility. Broad-spectrum chemotherapy drugs are problematic as breast
cancer cells develop resistance through selective loss of a novel target and
downregulation of apoptotic factors. A better understanding of the tumor
microenvironment offers new therapeutic opportunities to rescue the immune
response, inhibit cancer cell growth pathways, and subvert the tumor
microenvironment with little toxicity and side effects.
PMID- 26417206
TI - "Now I Can Do Better": A Study of Obese Women's Experiences Following a
Nonprescriptive Nutritional Intervention.
AB - The present study analyzed obese women's experiences following a nonprescriptive
nutritional intervention, implemented through a 1-year program based on the
Health at Every Size((r)) philosophy. We employed an action research method and
conducted three focus groups during the intervention. We identified five
interpretative axes across the focus groups, as follows: conflicts and
perceptions; gaining motivation, perspective, and positioning; becoming
autonomous eaters; acquiring tools; and the meetings between the nutritional
therapist and participant. Our findings revealed varying levels of readiness
among participants in adapting to the intervention and varying valuations of
achievements related to eating and health, independent of body-weight changes.
Participants reported benefiting from and expressed approval of the intervention.
Participants reported positive behavioral and attitudinal changes to their diet
and improvements to diet quality, diet structure, and consumption. Finally,
participants seemed to show increased autonomy concerning diet and indicated
increased confidence, comfort, flexibility, and positivity of attitude regarding
eating.
PMID- 26417207
TI - Robotic Approaches to Palatoplasty and the Treatment of Velopharyngeal
Dysfunction.
AB - The operative techniques used to address palatoplasty and velopharyngeal
dysfunction rely on traditional methods of surgical exposure and tissue handling.
As the role of robotic surgical systems has expanded, emphasis has shifted from
extirpative to reconstructive applications. We discuss the possible role of
surgical telemanipulation systems in the treatment of these diagnoses.
Furthermore, we present a feasibility study that addresses a commonly performed
treatment of velopharyngeal dysfunction-posterior pharyngeal flap (PPF). In
brief, PPFs were successfully performed on a small series of cadaveric human
specimens. The technical aspects of the procedure, including telemanipulator set
up, positioning, surgical instrumentation, and timing are described in detail.
All cadavers underwent successful performance of PPFs. Operative times were
within an acceptable range and use of the robotic system demonstrated a steep
learning curve. Many of the potential advantages and costs associated with
robotic surgical systems are discussed.
PMID- 26417205
TI - Selective Regulation of Oocyte Meiotic Events Enhances Progress in Fertility
Preservation Methods.
AB - Following early embryonic germ cell migration, oocytes are surrounded by somatic
cells and remain arrested at diplotene stage until luteinizing hormone (LH)
surge. Strict regulation of both meiotic arrest and meiotic resumption during
dormant stage are critical for future fertility. Inter-cellular signaling system
between the somatic compartment and oocyte regulates these meiotic events and
determines the follicle quality. As well as the collected number of eggs, their
qualities are also important for in vitro fertilization (IVF) outcome. In
spontaneous and IVF cycles, germinal vesicle (GV)-stage oocytes, premature GV
breakdown, and persistence of first meiotic arrest limit the reproductive
performance. Likewise, both women with premature ovarian aging and young cancer
women are undergoing chemoradiotherapy under the risk of follicle loss because of
unregulated meiotic events. Understanding of oocyte meiotic events is therefore
critical for the prevention of functional ovarian reserve. High levels of cyclic
guanosine monophophate (cGMP), cyclic adenosine monophophate (cAMP) and low
phosphodiesterase (PDE) 3A enzyme activity inside the oocyte are responsible for
maintaining of meiotic arrest before the LH surge. cGMP is produced in the
somatic compartment, and natriuretic peptide precursor C (Nppc) and natriuretic
peptide receptor 2 (Npr2) regulate its production. cGMP diffuses into the oocyte
and reduces the PDE3A activity, which inhibits the conversion of cAMP to the
5'AMP, and cAMP levels are enhanced. In addition, oocyte itself has the ability
to produce cAMP. Taken together, accumulation of cAMP inside the oocyte induces
protein kinase activity, which leads to the inhibition of maturation-promoting
factor and meiotic arrest also continues. By stimulating the expression of
epidermal growth factor, LH inhibits the Nppc/Npr2 system, blocks cGMP synthesis,
and initiates meiotic resumption. Oocytes lacking the functional of this pathway
may lead to persistence of the GV oocyte, which reduces the number of good
quality eggs. Selective regulation of somatic cell signals and oocyte meiotic
events enhance progress in fertility preservation methods, which may give us the
opportunity to prevent follicle loss in prematurely aging women and young women
with cancer are undergoing chemoradiotherapy.
PMID- 26417209
TI - Te Whiringa Ora: person-centred and integrated care in the Eastern Bay of Plenty,
New Zealand.
AB - Te Whiringa Ora is a community-based programme in New Zealand that facilitates
interdisciplinary care for patients and their family. It targets those with a
chronic disease whom have high inpatient admissions or emergency department
presentations. It is based in a rural part of New Zealand that has a large
indigenous population, and a relatively high level of social deprivation. The
programme makes use of culturally appropriate care coordinators, and uses
telephone support and tele-monitoring to aid self-management. The programme has
been running for three years and has shown a reduction on hospital presentations,
as compared to an equivalent population (not enrolled in the programme). This
case study outlines the programme, and focuses specifically on the implementation
processes, and lessons learnt.
PMID- 26417208
TI - Advances in the Treatment of Syndromic Midface Hypoplasia Using Monobloc and
Facial Bipartition Distraction Osteogenesis.
AB - Midface hypoplasia or retrusion remains a persistent feature of syndromic
craniosynostosis years after successful treatment of the cranium. Although
expansion of the cranial vault in infancy by traditional fronto-orbital
advancement, posterior expansion, or both, can treat the immediate intracranial
constriction, midface hypoplasia and its stigmata of exorbitism, sleep apnea,
central face concavity, and malocclusion remain suboptimally treated. Initial
enthusiasm for the procedures was tempered due to a high rate of infectious
complications; timing and indications for surgery continue to stir controversy.
During the last decade renewed interest with the monobloc and facial bipartition
procedure using distraction osteogenesis with either an internal or external
distraction system has decreased morbidity significantly. These procedures have
re-emerged as powerful and comprehensive tools in the treatment of syndromic
midface hypoplasia.
PMID- 26417210
TI - Bridging the chronic care gap: HealthOne Mt Druitt, Australia.
AB - HealthOne was part of a state-wide initiative to invest in new community-based
facilities for collocating services. The HealthOne Mount Druitt is a virtual hub
and spoke organisation established in 2006 in a socially disadvantaged part of
Western Sydney based out of a new community health hub. The model is based on
'virtual' care planning and aims to improve coordination of care for older people
with complex health needs, reduce unnecessary hospitalisations and ensure
appropriate referral to community and specialist health services. General
practitioner liaison nurses (GPLNs) work closely with clients as well as general
practitioners (GPs) and other health care providers. Primary health care
providers reported improved communication and coordination of services, and there
have been lower levels of utilisation of the emergency department (ED) for
patients following enrolment in the programme. HealthOne provides an example of
how a virtual organisation together with highly skilled care coordinators can
overcome some of the barriers to providing integrated care created by fragmented
funding streams and care delivery systems.
PMID- 26417211
TI - Managing high-risk patients: the Mass General care management programme.
AB - The Massachusetts General Care Management Program (Mass General CMP or CMP) was
designed as a federally supported demonstration to test the impact of intensive,
practice-based care management on high-cost Medicare fee-for-service (FFS)
beneficiaries-primarily older persons-with multiple hospitalisations and multiple
chronic conditions. The Massachusetts General Care Management Program operated
over a 6-year period in two phases (3 years each). It started during the first
phase at Massachusetts General Hospital, a major academic medical centre in
Boston, Massachusetts in collaboration with Massachusetts General Physicians
Organisation. During the second phase, the programme expanded to two more
affiliated sites in and around the Boston area, including a community hospital,
as well as incorporated several modifications primarily focused on the management
of transitions to post-acute care in skilled nursing facilities. At the close of
the demonstration in July 2012, Mass General Massachusetts General Care
Management Program became a component of a new Pioneer accountable care
organisation (ACO). The Massachusetts General Care Management Program is focused
on individuals meeting defined eligibility criteria who are offered care that is
integrated by a case manager embedded in a primary care practice. The
demonstration project showed substantial cost savings compared to fee-for-service
patients served in the traditional Medicare system but no impact on hospital
readmissions. The Massachusetts General Care Management Program does not rest
upon a "whole systems" approach to integrated care. It is an excellent example of
how an innovative care co-ordination programme can be implemented in an existing
health-care organisation without making fundamental changes in its underlying
structure or the way in which direct patient care services are paid for. The
accountable care organisation version of the Massachusetts General Care
Management Program includes the staffing structure, standards of practice,
collaborative approach to care transitions and information technology tools that
were used in the original demonstration project.
PMID- 26417212
TI - PRISMA: Program of Research to Integrate the Services for the Maintenance of
Autonomy. A system-level integration model in Quebec.
AB - The Program of Research to Integrate the Services for the Maintenance of Autonomy
(PRISMA) began in Quebec in 1999. Evaluation results indicated that the PRISMA
Project improved the system of care for the frail elderly at no additional cost.
In 2001, the Quebec Ministry of Health and Social Services made implementing the
six features of the PRISMA approach a province-wide goal in the programme now
known as RSIPA (French acronym). Extensive Province-wide progress has been made
since then, but ongoing challenges include reducing unmet need for case
management and home care services, creating incentives for increased physician
participation in care planning and improving the computerized client chart, among
others. PRISMA is the only evaluated international model of a coordination
approach to integration and one of the few, if not the only, integration model to
have been adopted at the system level by policy-makers.
PMID- 26417213
TI - Determinants of 25-Hydroxyvitamin D Concentrations in Infants and Toddlers.
AB - BACKGROUND: Resurgence of rickets and recognition of excessive prevalence of
hypovitaminosis D among all age groups in the western hemisphere have refocused
attention on vitamin D nutrition. OBJECTIVE: To examine the prevalence of
hypovitaminosis D [25-hydroxyvitamin D [25(OH)D] <30ng/mL] and characterize the
determinants of 25(OH)D concentrations in 8- to 24-month-old healthy infants and
toddlers living in Pittsburgh, Pennsylvania. METHODS: Serum 25(OH)D
concentrations were measured and dietary intake of vitamin D, mode of feeding,
summertime sun exposure characteristics, and skin color (sun-reactive skin type
and melanin index) were assessed. RESULTS: A total of 111 healthy 8- to 24-month
old children (mean age [+/-SD] 14.4 [+/-3.5] months; male, 51%; black, 67%) were
studied. Serum 25(OH)D concentration was <30 ng/mL in 16% (n=18) of the children.
Median (interquartile) 25(OH)D concentration was lower in children who were >= 13
months vs. <13 months of age [35 (31, 40.5) vs. 40 (35.8, 44.3) ng/mL, p=0.013];
with sun-reactive skin type IV and V vs. I, II, and III [36 (31, 41) vs. 44
(36.5, 48.5) ng/mL, p=0.001]; and examined during fall/winter vs. spring/summer
[35.5 (32.5, 38.5) vs. 39 (32.5, 44) ng/mL, p=0.05]. Age and skin type were
significant independent predictors of 25(OH)D. CONCLUSIONS: Concentrations of
25(OH)D tend to be lower in infants and toddlers during fall/winter, and in
children who are older (>=13 months vs. <13 months of age) and have darker skin
tone. Benefits of enhancement of 25(OH)D concentrations during fall/winter and in
children with higher sun-reactive skin type need further exploration.
PMID- 26417214
TI - Association of the virulence factors of Helicobacter pylori and gastric mucosal
interleukin-17/23 mRNA expression in dyspeptic patients.
AB - The molecular pathways that control Helicobacter pylori (Hp)-associated
inflammatory reaction are complex, but locally induced cytokines and virulence
factors seem to have a major role in maintaining the ongoing inflammation.
Therefore this study was aimed to evaluate the association of the virulence
factors of Hp and gastric mucosal interleukin-17/23 mRNA expression in dyspeptic
patients. Mucosal IL-17 and IL-23 mRNA expression in H. pylori infected and non
infected gastric biopsies were determined by real-time RT-PCR. Virulence factors,
vac-A and cag-A were evaluated using PCR. There was no significant difference in
mucosal IL-17 and IL-23 mRNA expression between H. pylori infected and non
infected patients. Their expression in mucosa did not correlate with chronic
gastritis and chronic active gastritis. IL-17 and IL-23 mRNA expression in mucosa
of patients with vacA m1 were significantly higher than those observed in
patients with vacA m2. The severity of polymorphonuclear infiltration and chronic
active gastritis was higher in cag-A positive than cag-A negative patients. H.
pylori infections carrying the vacA m1 allele have higher IL-17 and IL-23 mRNA
and the current study suggests that the virulence factor vacA allele's m1 are
important for the severe gastric inflammation.
PMID- 26417215
TI - Optimization of dilute acid pretreatment of water hyacinth biomass for enzymatic
hydrolysis and ethanol production.
AB - The present study was conducted for the optimization of pretreatment process that
was used for enzymatic hydrolysis of lignocellulosic biomass (Water Hyacinth,
WH), which is a renewable resource for the production of bioethanol with
decentralized availability. Response surface methodology has been employed for
the optimization of temperature ((o)C), time (hr) and different concentrations of
maleic acid (MA), sulfuric acid (SA) and phosphoric acid (PA) that seemed to be
significant variables with P < 0.05. High F and R (2) values and low P-value for
hydrolysis yield indicated the model predictability. The pretreated biomass
producing 39.96 g/l, 39.86 g/l and 37.9 g/l of reducing sugars during enzymatic
hydrolysis with yield 79.93, 78.71 and 75.9 % from PA, MA and SA treated
respectively. The order of catalytic effectiveness for hydrolysis yield was found
to be phosphoric acid > maleic acid > sulfuric acid. Mixture of sugars was
obtained during dilute acid pretreatment with glucose being the most prominent
sugar while pure glucose was obtained during enzymatic hydrolysis. The resulting
sugars, obtained during enzymatic hydrolysis were finally fermented to ethanol,
with yield 0.484 g/g of reducing sugars which is 95 % of theoretical yield (0.51
g/g glucose) by using commercial baker's yeast (Sacchromyces cerveasiae).
PMID- 26417216
TI - Scatter-search with support vector machine for prediction of relative solvent
accessibility.
AB - Proteins have vital roles in the living cells. The protein function is almost
completely dependent on protein structure. The prediction of relative solvent
accessibility gives helpful information for the prediction of tertiary structure
of a protein. In recent years several relative solvent accessibility (RSA)
prediction methods including those that generate real values and those that
predict discrete states have been developed. The proposed method consists of two
main steps: the first one, provided subset selection of quantitative features
based on selected qualitative features and the second, dedicated to train a model
with selected quantitative features for RSA prediction. The results show that the
proposed method has an improvement in average prediction accuracy and training
time. The proposed method can dig out all the valuable knowledge about which
physicochemical features of amino acids are deemed more important in prediction
of RSA without human supervision, which is of great importance for biologists and
their future researches.
PMID- 26417217
TI - Comparing the effect of clofibrate and phenobarbital on the newborns with
hyperbilirubinemia.
AB - The aim of treating hyperbilirubinemia is preventing the serum bilirubin to reach
neurotoxic levels, which is done by phototherapy or blood transfusion. However,
pharmacological treatments still remain vague. Therefore the effects of adding
either clofibrate or phenobarbital on treatment outcomes was evaluated in icteric
non-hemolitic newborns. Ninety neonates were divided in three groups. Two groups
were prescribed 100 mg/kg clofibrate or 5 mg/kg phenobarbital orally as single
dose on arrival, in addition to phototherapy. The control group only received
phototherapy. Serum bilirubin was evaluated at the reception and 12, 24, 48 and
72 hours after beginning of drug therapy. Total bilirubin levels decreased in
treated groups compared with the control group in all samples taken (12, 24, 48
and 72 hours). Clofibrate effect in decreasing bilirubin level was more prominent
(14 % and 32 % after 12 and 72 h respectively). In addition duration of
hospitalization and length of phototherapy decreased in clofibrate and
phenobarbital groups compared with control group (1.5, 2 days respectively, vs.
2.6 days). Therefore using clofibrate and phenobarbital in icteric neonates are
supportive not only by decreasing the serum bilirubin level, but also by
lessening the duration of hospitalization and phototherapy. Thus in addition to
cost benefits for the patient these drugs can reduce the risks of transfusion,
and clofibrate seems more promising in this regard.
PMID- 26417218
TI - Prevalence of ESBL, AmpC beta-lactamases and MRSA among uropathogens and its
antibiogram.
AB - Urinary tract infections (UTIs) are one of the most common bacterial infections
in humans. Current knowledge on antimicrobial susceptibility pattern is essential
for appropriate therapy. Therefore the aim of the present study was to determine
the distribution and antibiotic susceptibility pattern of bacterial strains, with
special reference to ESBL, AmpC beta-lactamase and MRSA production. A total of
325 clinical isolates were collected from UTI patients from various tertiary care
hospitals over a period of 6 months (June 2011 to December 2011). The
antimicrobial susceptibility to various drugs was studied by the disc diffusion
method as guided by CLSI guidelines. Confirmation of the extended spectrum beta
lactamase (ESBL), AmpC beta-lactamase and methicillin resistant Staphylococcus
aureus (MRSA) production was done by an E-test respectively. Of the 325 isolates,
225 were characterized as gram negative and 77 isolates as S. aureus isolates.
The majority (69.3 %) of the isolates were from females compared to males (30.7
%). Prevalence of ESBL and AmpC beta-lactamase and the coexistence of the
phenotype (ESBL+ AmpC beta-lactamase) and MRSA in the urinary isolates were found
to be 48.9 %, 20.4 %, 6.2 % and 27.5 % respectively. Ampicillin/sulbactam,
norfloxacin should be no longer considered as first line of drugs for UTI,
because of high resistance. Parentral drugs such as aminoglycosides, carbapenems
and piperacillin/tazobactum can be the alternative choice for complicated UTI.
Also, control measures such as judicious use of antibiotics, formulation of
infection committee may control the spread of resistance.
PMID- 26417219
TI - Effects of drought stress on the seed germination and early seedling growth of
the endemic desert plant Eremosparton songoricum (Fabaceae).
AB - Eremosparton songoricum (Litv.) Vass. is an endemic and extremely drought
resistant desert plant with populations that are gradually declining due to the
failure of sexual recruitment. The effects of drought stress on the seed
germination and physiological characteristics of seeds and seedlings were
investigated. The results showed that the germination percentage decreased with
an increase of polyethylene glycol 6000 (PEG) concentration: -0.3 MPa (5 % PEG)
had a promoting effect on seed germination, -0.9 MPa (15 % PEG) dramatically
reduced germination, and -1.8 MPa (30 % PEG) was the threshold for E. songoricum
germination. However, the contents of proline and soluble sugars and the activity
of CAT increased with increasing PEG concentrations. At the young seedling stage,
the proline content and CAT, SOD and POD activities all increased at 2 h and then
decreased; except for a decrease at 2 h, the MDA content also increased compared
to the control (0 h). These results indicated that 2 h may be a key response time
point for E. songoricum to resist drought stress. The above results demonstrate
that drought stress can suppress and delay the germination of E. songoricum and
that the seeds accumulate osmolytes and augment the activity of antioxidative
enzymes to cope with drought injury. E. songoricum seedlings are sensitive to
water stress and can quickly respond to drought but cannot tolerate drought for
an extended period. Although such physiological and biochemical changes are
important strategies for E. songoricum to adapt to a drought-prone environment,
they may be, at least partially, responsible for the failure of sexual
reproduction under natural conditions.
PMID- 26417220
TI - The effects of ursolic acid on cytokine production via the MAPK pathways in
leukemic T-cells.
AB - Ursolic acid (UA) is a pentacyclic triterpenoid carboxylic acid that is found in
plants and herbal products. It is one of the chemopreventive agents, which can
suppress cancer cell proliferation and induce apoptosis. UA possesses various
biological activities including anticancer, anti-inflammatory, anti-oxidative and
hepatoprotective activity. We investigated the effect of UA on cytokine
production via the MAPK pathways in Jurkat leukemic T-cells, showing that UA
inhibited cell growth and proliferation of Jurkat cells, as well as suppressing
PMA/PHA induced IL-2 and TNF-alpha production in a concentration and time
dependent manner. The inhibition of IL-2 and TNF-alpha production by UA involved
the c-Jun N-terminal kinase (JNK) pathway, but not the extracellular-signal
regulated protein kinase (ERK) pathway. Future utilization of UA as a
chemopreventive or therapeutic agent may provide an alternative option for
leukemia treatments.
PMID- 26417221
TI - Modulatory effect of semelil (ANGIPARSTM) on isoproterenol induced cardiac
injury.
AB - Administration of semelil (ANGIPARSTM) has been successful in the treatment of
diabetic foot ulcer. Considering the improvement of blood flow and anti
inflammatory effect that are attributed to this drug, we investigated its effect
on cardiovascular performance in rabbits with isoproterenol (ISO) induced
myocardial injury. Animal groups included: control group; ISO group, received ISO
50 mg/kg s.c. for two consecutive days; S1+ISO, S5+ISO and S10+ISO groups,
received semelil 1, 5, and 10 mg/kg/day i.p. respectively, 30 min before ISO. On
the 3(rd) day, electrocardiogram (ECG) and hemodynamic parameters were recorded;
blood samples were taken and hearts were removed for lab investigations. ISO
induced heart injury, ECG disturbance, raise of cardiac troponin I and
significant decrease in LVSP (p<0.05), +dp/dt max (p<0.01), -dp/dt max (p<0.05)
along with increase of LVEDP (p<0.01). Semelil had no significant effects on ECG
and plasma cardiac troponin I. Impairment of +dp/dt max and -dp/dt max was
significantly improved in S5+ISO and S10+ISO groups (P<0.05 versus ISO). In
addition, LVSP and LVEDP was somewhat recovered in these groups, although semelil
(1 mg/kg/day) to some extent exacerbated the myocardial lesions induced by ISO
(P<0.05). Therefore, in stressful conditions, semelil may improve myocardial
contractility; however, it may aggravate the severity of injury.
PMID- 26417222
TI - Combined 3D-QSAR modeling and molecular docking study on multi-acting quinazoline
derivatives as HER2 kinase inhibitors.
AB - A series of new quinazoline derivatives has been recently reported as potent
multi-acting histone deacetylase (HDAC), epidermal growth factor receptor (EGFR),
and human epidermal growth factor receptor 2 (HER2) inhibitors. HER2 is one of
the major targets for the treatment of breast cancer and other carcinomas. Three
dimensional structure-activity relationship (3D-QSAR) is a well-known technique,
which is used to drug design and development. This technique is used for
quantitatively predicting the interaction between a molecule and the active site
of a specific target. For each 3D-QSAR study, a three-dimensional model is
created from a large curve fit to find a fitting between computational
descriptors and biological activity. This model could be used as a predictive
tool in drug design. The best model has the highest correlation between
theoretical and experimental data. Self-Organizing Molecular Field Analysis
(SOMFA), a grid-based and alignment-dependent 3D-QSAR method, is employed to
study the correlation between the molecular properties and HER2 inhibitory
potency of the quinazoline derivatives. Before presentation of inhibitor
structures to SOMFA study, conformation of inhibitors was determined by
AutoDock4, HyperChem and AutoDock Vina, separately. Overall, six independent
models were produced and evaluated by the statistical partial least square (PLS)
analysis. Among the several generated 3D-QSARs, the best model was selected on
the basis of its statistical significance and predictive potential. The model
derived from the superposition of docked conformation with AutoDock Vina with
reasonable cross-validated q(2) (0.767), non cross-validated r(2) (0.815) and F
test (97.22) values showed a desirable predictive capability. Analysis of SOMFA
model could provide some useful information in the design of novel HER2 kinase
inhibitors with better spectrum of activity.
PMID- 26417223
TI - Post transplant lymphoproliferative disorder: a case series and review of
literature.
AB - Post-transplant lymphoproliferative disorder (PTLD) is a recognized complication
exclusive to solid organ transplant recipients and carries a high mortality. We
retrospectively reviewed records of all renal transplant recipients under follow
up at our institution over the last seven years (2005-2011). We reviewed the
patient characteristics, immunosuppression regimen and risk factors for the
development of PTLD and its outcomes in our transplant cohort. Four out of 63
patients were diagnosed with PTLD. PTLD was incidentally diagnosed on a
transplant biopsy that was performed for an unexplained rise in serum creatinine
in three patients. The fourth patient presented with left submandibular
lymphadenopathy. Majority presented within 18 months of renal transplantation.
After the diagnosis of PTLD on graft biopsy, all patients were fully investigated
and two patients had systemic involvement. In the patients with systemic
involvement, reduction of immunosuppression and anti B cell therapy with
Rituximab was used with good success. The patient with submandibular
lymphadenopathy received chemotherapy in addition to reduction of
immunosuppression. Three PTLD cases were polyclonal and diagnosed early whereas
the fourth case was monoclonal. PTLD can sometimes be incidentally diagnosed on
an allograft biopsy performed for rejection. The incidence of PTLD in our centre
is higher than reports from other centres but our outcome is good if recognised
and treated early.
PMID- 26417224
TI - Antioxidative, antimicrobial and cytotoxic properties of Isatis floribunda Boiss.
ex Bornm. extracts.
AB - The Isatis species has antibacterial, anticancer and antiviral properties and
these important endemic plants grow widely in various parts of Anatolian-Turkey.
In the present study, the antioxidant activities of Isatis floribunda Boiss. ex
Bornm. flower and root extracts were determined with total antioxidant activity,
free radical scavenging activity, ferric ion reducing power, and cupric ion
reducing antioxidant capacity assay. The total phenolic compounds and flavonoids
were also examined for the extracts. The antimicrobial activities of the extracts
were investigated by using the disc diffusion and microdilution-broth methods
against human and fish pathogen microorganisms. The phenolic composition of I.
floribunda root methanolic extract was analyzed by high performance liquid
chromatography (HPLC). The major component in the extract was cholorogenic acid
(1980.20 ug/g). The cytotoxic effect of the methanolic root extract was also
tested on human breast cell (MCF12A). The results showed that I. floribunda could
be used as a natural source in the food and feed industry and clinical and food
chemistry, and that the antimicrobial agents could be used against human and fish
pathogens.
PMID- 26417225
TI - Novel inhibitor discovery against aromatase through virtual screening and
molecular dynamic simulation: a computational approach in drug design.
AB - Inhibition of aromatase (CYTP450) as a key enzyme in the estrogen biosynthesis
could result in regression of estrogen-dependent tumors and even preventing the
promotion of breast cancer. Although today potent steroid and non-steroid
inhibitors of aromatase are available, isoflavanone derivatives as natural
compounds with least side effects have been described as the candidate for a new
generation of aromatase inhibitors. 2a as an isoflavanone derivative is the most
potent inhibitor of aromatase, synthesized by Bonfield et al. (2012[7]). In our
computational study, the mentioned compound was used as the template for virtual
screening. Between 286 selected compounds with 70 % of structural similarity to
2a, 150 of them showed lower docking energy in comparison with 2a. Compound 2a_1
with 11.2 kcal/mol had the lowest docking energy. Interaction of 2a_1 with
aromatase was further investigated and compared with 2a and androstenedione (ASD)
as a natural substrate of aromatase, through 20 ns of molecular dynamic
simulation. Analysis of trajectories showed, while ASD interacts with aromatase
through hydrogen bonds and 2a just interacts via hydrophobic forces, 2a_1 not
only accommodates in the hydrophobic active site of aromatase in a suitable
manner but it also makes a stable coordination with iron atom of aromatase heme
group via OB.
PMID- 26417226
TI - Preventive effect of N-acetylcysteine in a mouse model of steroid resistant acute
exacerbation of asthma.
AB - Oxidative stress appears to have an important role in glucocorticoid
insensitivity, as a crucial problem in asthma therapy. We studied the preventive
effect of antioxidant N-acetylcysteine (NAC) on the airway hyper-responsiveness
(AHR) and the accumulation of inflammatory cells in the airways in an animal
model of steroid resistant acute exacerbation of asthma. Systemically sensitized
Balb/C mice were exposed to Ovalbumin aerosol on days 13, 14, 15 and 16, followed
by intratracheal lipopolysaccharide (LPS) to induce acute exacerbation. NAC
(intraperitoneal, 320 mg/kg 30 min before and 12 hours after each challenge)
reduced hyper-responsiveness with/out dexamethasone. LPS application caused
neutrophilia in bronchoalveolar lavage fluid (BALF) and eosinophil count was
higher than respective control in BALF as well as neutrophils after dexamethasone
treatment. NAC significantly decreased neutrophil and eosinophil count in BALF as
well as inflammatory cytokines (IL-13 and IL-5).We concluded that addition of NAC
to asthma therapy has beneficial preventive effects in an animal model of steroid
resistant acute exacerbation of asthma.
PMID- 26417228
TI - Computational modeling and validation studies of 3-D structure of neuraminidase
protein of H1N1 influenza A virus and subsequent in silico elucidation of piceid
analogues as its potent inhibitors.
AB - Emergence of the drug resistant variants of the Influenza A virus in the recent
years has aroused a great need for the development of novel neuraminidase
inhibitors for controlling the pandemic. The neuraminidase (NA) protein of the
influenza virus has been the most potential target for the anti-influenza.
However, in the absence of any experimental structure of the drug targeting NA
protein of H1N1 influenza A virus as zanamivir and oseltamivir, the comprehensive
study of the interaction of the drug molecules with the target protein has been
missing. Hence in this study a computational 3-D structure of neuraminidase of
H1N1 influenza A virus has been developed using homology modeling technique, and
the same was validated for its reliability by ProSA web server in term of energy
profile & Z scores and PROCHECK program followed by Ramachandran plot. Further,
the developed 3-D model had been employed for docking studies with the class of
compounds as Piceid and its analogs. In this context, two novel compounds
(ChemBank ID 2110359 and 3075417) were found to be more potent inhibitors of
neuraminidase than control drugs as zanamivir and oseltamivir in terms of their
robust binding energies, strong inhibition constant (Ki) and better hydrogen bond
interactions between the protein-ligand complex. The interaction of these
compounds with NA protein has been significantly studied at the molecular level.
PMID- 26417227
TI - Cannabis-induced impairment of learning and memory: effect of different nootropic
drugs.
AB - Cannabis sativa preparations are the most commonly used illicit drugs worldwide.
The present study aimed to investigate the effect of Cannabis sativa extract in
the working memory version of the Morris water maze (MWM; Morris, 1984[43]) test
and determine the effect of standard memory enhancing drugs. Cannabis sativa was
given at doses of 5, 10 or 20 mg/kg (expressed as Delta(9)-tetrahydrocannabinol)
alone or co-administered with donepezil (1 mg/kg), piracetam (150 mg/ kg),
vinpocetine (1.5 mg/kg) or ginkgo biloba (25 mg/kg) once daily subcutaneously
(s.c.) for one month. Mice were examined three times weekly for their ability to
locate a submerged platform. Mice were euthanized 30 days after starting cannabis
injection when biochemical assays were carried out. Malondialdehyde (MDA),
reduced glutathione (GSH), nitric oxide, glucose and brain monoamines were
determined. Cannabis resulted in a significant increase in the time taken to
locate the platform and enhanced the memory impairment produced by scopolamine.
This effect of cannabis decreased by memory enhancing drugs with piracetam
resulting in the most-shorter latency compared with the cannabis. Biochemically,
cannabis altered the oxidative status of the brain with decreased MDA, increased
GSH, but decreased nitric oxide and glucose. In cannabis-treated rats, the level
of GSH in brain was increased after vinpocetine and donepezil and was markedly
elevated after Ginkgo biloba. Piracetam restored the decrease in glucose and
nitric oxide by cannabis. Cannabis caused dose-dependent increases of brain
serotonin, noradrenaline and dopamine. After cannabis treatment, noradrenaline is
restored to its normal value by donepezil, vinpocetine or Ginkgo biloba, but
increased by piracetam. The level of dopamine was significantly reduced by
piracetam, vinpocetine or Ginkgo biloba. These data indicate that cannabis
administration is associated with impaired memory performance which is likely to
involve decreased brain glucose availability as well as alterations in brain
monoamine neurotransmitter levels. Piracetam is more effective in ameliorating
the cognitive impairments than other nootropics by alleviating the alterations in
glucose, nitric oxide and dopamine in brain.
PMID- 26417229
TI - Effect of subclinical, clinical and supraclinical doses of calcium channel
blockers on models of drug-induced hepatotoxicity in rats.
AB - Drug-related hepatotoxicity is the leading cause of acute liver failure, and
hepatic problems are responsible for a significant number of liver
transplantations and deaths worldwide. Calcium has been associated with various
metabolic processes that lead to cell death and apoptosis, and increased
cytosolic Ca(2+) has been implicated in hepatotoxicity. This study was designed
to investigate the effects of calcium channel blockers (CCBs) on isoniazid
rifampicin, zidovudine and erythromycin-induced hepatotoxicity in rats. Treatment
groups comprised control, hepatotoxicant, hepatotoxicant along with each of
silymarin, nifedipine, verapamil and diltiazem at subclinical, clinical and
supraclinical doses. A day to the end of treatment for each model, rats were
subjected to the hexobarbitone-induced hypnosis test. On the last days of
treatment, blood samples were collected and serum was analyzed for relevant
biochemical parameters. Animals were sacrificed after blood collection and livers
were harvested, and samples obtained for in vivo antioxidant indices assay and
histopathology. The hepatotoxicants significantly increased serum levels of
aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline
phosphatase (ALP), as well as duration of sleep in the hypnosis test. These drugs
significantly reduced the hepatic levels of reduced glutathione (GSH), superoxide
dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased the
level of malondialdehyde (MDA). The CCBs at the various doses significantly
reversed the effects of isoniazid-rifampicin, zidovudine and erythromycin. The
results obtained in this study suggest that the CCBs possess hepatoprotective
activity in drug-induced hepatotoxicity and may be beneficial at the subclinical
and clinical doses.
PMID- 26417230
TI - Blocking of rat hippocampal Cx36 by quinine accelerates kindling epileptogenesis.
AB - There are abundant studies indicating that blocking gap junctions (GJs)
containing connexin 36 (Cx36) inhibit seizures. However, recent evidences
demonstrate proconvulsant effect of such intervention. Electrical coupling
between GABAergic interneurons in CA1 region of hippocampus is mediated through
Cx36 GJs. We investigated effect of quinine, a specific blocker of Cx36, on the
seizure severity and epileptogenesis in amygala kindling model of epilepsy in
rats. Quinine (1, 50, 100, 500 and 2000 uM/rat) was injected directly into the
CA1 and kindled seizure parameters including behavioral seizure stage, duration
of evoked afterdischarges, and duration of generalized seizures behavior were
recorded 10 min afterward. Moreover, quinine (1, 30, and 100 uM/rat) was injected
intra CA1 once daily during kindling development. At the doses used, quinine had
no significant effect on amygdala-kindled seizures. However, quinine 100 uM
significantly accelerated kindling rate. Blockade of Cx36 GJs coupling and
consequent disruption of inhibitory transmission in GABAergic interneurons in CA1
area seems to be responsible for the antiepileptogenic effect of quinine.
PMID- 26417231
TI - Fenugreek seed extract treats peripheral neuropathy in pyridoxine induced
neuropathic mice.
AB - Trigonella foenum graecum commonly known as Fenugreek exerts normoglycemic and
insulinotropic effects in humans by compounds from its seed and leaf extracts.
Some studies reported that treating pregnant mice with fenugreek seed could cause
toxic effects on the nervous system of its pubs during developmental growth,
while in some other studies neuroprotective properties were considered for it.
Safety of anti-diabetic drugs for nervous system is very important because
peripheral neuropathy is a common complication of diabetes and hazardous drugs
could worsen it. In this study, the effect of treatment with fenugreek seed
extract on the function of sciatic nerves of neuropathic mice was evaluated.
Neuropathy was induced in male mice by pyridoxine intoxication. After that,
animals were treated with 0.2, 2 and 20 mg/kg of hydro-alcoholic extract of
fenugreek seeds for 10 days, tail flick, electrophysiological and histological
assays were performed to evaluate the effect of fenugreek seed extract on
function of the peripheral nerves. Our data showed that fenugreek has anti
neuropathic effect and restores the function of nerve fibers. Results of
electrophysiological recordings stated that the highest rate of healing was
occurred in 20 mg/kg fenugreek extract treated animals. In conclusion, findings
of the present study demonstrate that treatment with fenugreek seed extract can
potentially facilitate healing from pyridoxine induced peripheral neuropathy in
mice.
PMID- 26417233
TI - Protective effect of Tribulus terrestris L. fruit aqueous extracton lipid profile
and oxidative stress in isoproterenol induced myocardial necrosis in male albino
Wistar rats.
AB - The objective of the present study was to evaluate the possible protective
effects of Tribulus terrestris fruit aqueous extract (TTFAEt) on lipid profile
and oxidative stress in isoproterenol (ISO) induced myocardial necrosis in albino
Wistar rats. Albino Wistar rats were divided into normal control, TTFAEt alone
treated, ISO control and pretreated (TTFAEt+ISO) groups. The extract was
administered at a dose of 50 mg/kg body weight for 40 days orally by gavage and
ISO was administered at a dose of 85 mg/kg body weight for two consecutive days
intraperitoneally at an interval of 24 h. ISO induced myocardial infarction (MI)
was confirmed by disturbances in serum lipid profile, heart tissue lipid
peroxidation and antioxidant enzyme levels. There was a significant increase in
the levels of serum total cholesterol (32.60 %), triglycerides (41.30 %), very
low density lipoproteins (81.81 %), low density lipoproteins (84%) and
phospholipids (38.88 %) and a significant decrease in the levels of high density
lipoproteins (33.33 %) in the ISO control group when compared to normal controls.
Additionally, there is a significant decrease in the levels of heart tissue
antioxidant enzymes such as superoxide dismutase, catalase, glutathione
reductase, glutathione peroxidase and depletion of reduced glutathione, which
indicates enhanced lipid peroxidation(172 %). Pretreatment with extract
significantly showed a protective effect against ISO altered lipid profile, lipid
peroxidation and antioxidant enzyme levels. The present study showed therapeutic
effect of TTFAEt on lipid profile and oxidative stress in isoproterenol (ISO)
induced myocardial necrosis in experimental rats.
PMID- 26417232
TI - Coriandrum sativum L. seed extract mitigates lipotoxicity in RAW 264.7 cells and
prevents atherogenic changes in rats.
AB - This study was designed to assess the efficacy of Coriandrum sativum L. (CS) in
preventing in vitro low density lipoprotein (LDL) oxidation mediated macrophage
modification. Further, an in vivo study was also conducted to confirm upon the
efficacy of CS seed extract in alleviating pathophysiological alterations of high
cholesterol diet induced atherosclerosis in rats. Copper mediated cell free
oxidation of LDL accounted for elevated indices of malondialdehyde (MDA), lipid
hydroperoxide (LHP)and protein carbonyl (PC) and a progressive increment in
conjugate diene (CD) levels whereas, reverse set of changes were recorded in
presence of CS extract. Cell mediated LDL oxidation (using RAW 264.7 cells)
accounted for lowered MDA production and oxidized LDL (Ox-LDL) mediated cell
death in presence of CS extract and the same was attributed to its potent
antioxidant and free radical scavenging potentials. High cholesterol fed
atherogenic rats showed elevated lipid indices, evidences of LDL oxidation,
plaque formation in thoracic aorta. The same was further validated with
immunostaining of cell adhesion molecules and hematoxylin and eosin (HXE)
staining. However, co-supplementation of CS to atherogenic rats recorded
significant lowering of the above mentioned parameters further strengthening the
claim that CS extract is instrumental in preventing onset and progression of
atherosclerosis.
PMID- 26417234
TI - Synthesis of novel dopamine derived multidirectional ligands from cyanuric
chloride: structural and antimicrobial studies.
AB - Two monopodal (2,4-dichloro-6-(3-hydroxytyramine)-1,3,5-triazine) and tripodal
(2,4,6-(3-hydroxytyramine)-1,3,5-triazine) s-triazine derivatives were prepared
through the reaction of cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) and 3
hydroxytyramine hydrochloride (dopamine hydrochloride). The structures of the
compounds were identified by FT-IR, 1H NMR, 13C NMR, thermal analysis and
elemental analysis. Their antimicrobial activities were carried out using the
broth microdilution method in dimethyl sulfoxide (DMSO): Phosphate Buffered
Saline (PBS) against eight bacteria and one yeast. The results of the test were
compared with ampicillin. It was determined that CCDOP1, CCDOP3 and DOP have
significant antibacterial and antifungal activity. These three chemicals revealed
strong antibacterial activity against the E. coli and S. aureus strains used in
the study. S. aureus was the most sensitive strain against dopamine hydrochloride
and E. coli was the most sensitive bacteria against CCDOP1.
PMID- 26417235
TI - Factors affecting the adoption of healthcare information technology.
AB - In order to improve the quality and performance of healthcare services,
healthcare information technology is among the most important technology in
healthcare supply chain management. This study sets out to apply and test the
Unified Theory of Acceptance and Use of Technology (UTAUT), to examine the
factors influencing healthcare Information Technology (IT) services. A structured
questionnaire was developed and distributed to healthcare representatives in each
province surveyed in Thailand. Data collected from 400 employees including
physicians, nurses, and hospital staff members were tested the model using
structural equation modeling technique. The results found that the factors with a
significant effect are performance expectancy, effort expectancy and facilitating
conditions. They were also found to have a significant impact on behavioral
intention to use the acceptance healthcare technology. In addition, in Thai
provincial areas, positive significance was found with two factors: social
influence on behavioral intention and facilitating conditions to direct using
behavior. Based on research findings, in order for healthcare information
technology to be widely adopted and used by healthcare staffs in healthcare
supply chain management, the healthcare organizational management should improve
healthcare staffs' behavioral intention and facilitating conditions.
PMID- 26417236
TI - 5,10-methylene tetrahydrofolate reductase C677T gene polymorphism, homocysteine
concentration and the extent of premature coronary artery disease in southern
Iran.
AB - Elevated level of plasma homocysteine (Hcy) has been identified as an independent
risk factor for coronary artery disease (CAD). Furthermore, numerous studies have
documented the influences of a common polymorphism (C677T) of
methylenetetrahydrofolate reductase (MTHFR) on homocysteine levels. However the
relationship between this mutation and cardiovascular diseases (CVD) has remained
as a controversial issue. The present study was undertaken to investigate the
relationship between C677T polymorphism of MTHFR gene, plasma total Hcy levels
and the number of affected vessels as a criterion for the extent of CAD. MTHFR
genotypes and plasma homocysteine (HCY) concentrations were examined in 231
patients and 300 healthy subjects who underwent diagnostic coronary angiography.
A multiple linear regression analysis was performed to identify the predictors of
Hcy levels whereas logistic regression model was built to determine the
association of Hcy quartiles with the risk of CAD adjusted for risk factors. The
prevalence of MTHFR genotypes was similar between CAD patients and non-CAD
individuals while the geometric mean of Hcy values was significantly higher in
patient group (14.13 +/- 4.11 MUmol/l) than in control group (10.19 +/- 3.52
MUmol/l) (P < 0.001). Moreover, unlike the MTHFR polymorphism, Hcy concentration
increased with increasing number of stenosed vessels and the CAD risk increased
about 2 folds in the top two Hcy quartiles (>= 17.03 and 13.20-17.02 MUmol/l)
compared with the lowest quartile (<= 9.92 MUmol/l) after controlling for
conventional risk factors (P<0.001 for both). Our data suggest that
hyperhomocysteinaemia (HHcy) is significantly associated to CAD risk increase as
well as to the extent of coronary atherosclerosis.
PMID- 26417237
TI - Activation of sphingosine 1-phosphate receptor-1 by SEW2871 improves cognitive
function in Alzheimer's disease model rats.
AB - Sphingosine-1 phosphate (S1P) is involved in a variety of cellular processes via
activation of S1P receptors (S1PRs; S1PR1 to S1PR5) that are highly expressed in
the brain. It has been shown that the level of S1P is reduced in the brain of
Alzheimer's disease (AD) patients. However, there is no study designed to
evaluate the expression of S1PRs in AD brains. The objectives of the present work
are (1) to examine the expression of S1PR1-3 in the hippocampus of beta amyloid
(Abeta) 1-42 injected rats and (2) to clarify the effects of chronic S1PR1
activation on S1PR1-3 levels, spatial memory deficit and hippocampal damage in AD
rats. SEW2871, the S1PR1 selective agonist, repeatedly was injected
intraperitoneally during a period of two weeks. Upon Western Blot data bilateral
intrahippocampal injection of Abeta1-42 decreased the expression of S1PR1 while
increased S1PR2 level and did not affect that of S1PR3. We found that chronic
administration of SEW2871 inhibited the reduction of S1PR1 expression and
ameliorated spatial memory impairment in the Morris water maze task in rats. In
addition, SEW2871 attenuated the Abeta1-42-induced hippocampal neuronal loss
according to Nissl staining findings. Data in the current study highlights the
importance of S1PR1 signaling pathway deregulation in AD development and suggests
that activation of S1PR1 may represent a potential approach for developing new
therapeutics to manage memory deficit and apoptosis associated with
neurodegenerative disorders such as AD.
PMID- 26417238
TI - Acceleration of pro-caspase-3 maturation and cell migration inhibition in human
breast cancer cells by phytoconstituents of Rheum emodi rhizome extracts.
AB - The aggressive nature of estrogen receptor (ER)-negative breast cancer subtype
obligates for innovative targeted therapies. The present study aimed to
investigate the phytoconstituents and specific anticancer activities of Rheum
emodi rhizome, a known food source used locally to treat various ailments.
Petroleum ether extracts (hot [PHR] and cold [PCR]) of R. emodi, exhibited
significant free radical scavenging potentials through DPPH and reducing power
assays, rendering them as good sources of antioxidants. The extracts, PHR and PCR
had shown significant (P < 0.05) cancer-cell-specific cytotoxicity in the assayed
cells (MDA-MB-231 [breast carcinoma] and WRL-68 [non-tumoral]) at 100 MUg/ml, and
50 and 100 MUg/ml concentrations respectively. Extracts also induced fervent
apoptosis in ER-negative cells (MDA-MB-231) compared to ER-positive subtype (MCF
7), and found to involve CPP32/caspase-3 in its apoptosis induction mechanism.
Moreover, extracts had an inevitable potential to inhibit the migration of
metastatic breast cancer cells (MDA-MB-231) in vitro. Further, the active
principles of extracts were identified through HPLC and GC-MS analysis to reveal
major polyphenolics, 4,7-Dimethyl-(octahydro)indolo[4,3-fg]quinolin-10-one, 5-Oxo
isolongifolene, Valencene-2, and other quinone, quinoline and anthraquinone
derivatives. The extracts are thus good candidates to target malignant ER
negative breast cancer, and the identified phytoconstituents could be eluted in
further exploratory studies for use in dietary-based anti-breast cancer
therapies.
PMID- 26417239
TI - Effect of drought on safflower natural dyes and their biological activities.
AB - Drought is the main abiotic constraint that affects crop species behaviour
regarding bio-chemical responses. The current study was conducted to examine the
effect of water deficit on growth, phenolic and carotenoid contents as well as
the antioxidant and antimicrobial activities of two Carthamus tinctorius
varieties (Jawhara and 104) flowers. Hence, plants were treated with different
levels of water deficit: control (100 %), moderate water deficit (50 %) and
severe water deficit (25 %). Obtained results showed that plant growth was
significantly (p < 0.05) reduced under 50 %. Drought increased flower phenolic
acids contents especially gallic acid where they increased significantly (p <
0.05) by 2.73 fold (104) and by 2.87 fold (Jawhara) with respect to controls
under 50 %. However, the amounts of this major compound were reduced at 25 % by
9.66 % (104) and 3.83 % (Jawhara). Similar to phenolic compounds, total
carotenoid content was at its highest level especially for Jawhara with an
increase by 35.19 % at 50 %. On the other hands, C. tinctorius flowers extracts
exhibited high antiradical activity as compared to BHT. A gradual increase by
35.29 % (Jawhara) and 33.33 % (104) especially under 25 % was observed. Moreover,
under 50 %, the antimicrobial activity increased significantly (p < 0.05) by 30 %
and 10.05 % against Aspergillus carbonarus and Pseudomonas aerogenosa,
respectively. Taken together, our findings suggest that C. tinctorius could be a
raw material for production of natural dyes under moderate salinity conditions.
PMID- 26417240
TI - Automatic quantitative analysis of morphology of apoptotic HL-60 cells.
AB - Morphological identification is a widespread procedure to assess the presence of
apoptosis by visual inspection of the morphological characteristics or the
fluorescence images. The procedure is lengthy and results are observer dependent.
A quantitative automatic analysis is objective and would greatly help the routine
work. We developed an image processing and segmentation method which combined the
Otsu thresholding and morphological operators for apoptosis study. An automatic
determination method of apoptotic stages of HL-60 cells with fluorescence images
was developed. Comparison was made between normal cells, early apoptotic cells
and late apoptotic cells about their geometric parameters which were defined to
describe the features of cell morphology. The results demonstrated that the
parameters we chose are very representative of the morphological characteristics
of apoptotic cells. Significant differences exist between the cells in different
stages, and automatic quantification of the differences can be achieved.
PMID- 26417242
TI - Evaluation of adenosine deaminase (ADA) isoenzymes activity and tumor necrosis
factor-alpha (TNFalpha) concentration in chronic heart failure.
AB - INTRODUCTION: Chronic heart failure (CHF) has recently been considered as an
inflammatory disease. Enhanced production of tumor necrosis factor-alpha
(TNFalpha) in CHF patients has been proved. To compensate deleterious effects of
TNalpha, the concentration of adenosine is increased in CHF. However, concurrent
determination of serum TNFalpha and enzymatic activities of ADA and its ADA1 and
ADA2 isoenzymes, as the main regulators of adenosine concentration, has not yet
been carried out. MATERIALS AND METHODS: Blood samples were collected from 52 CHF
patients and 55 healthy controls. Laboratory routine tests were performed, and
after determining the concentration of TNFalpha, total ADA (tADA) as well as ADA1
and ADA2 isoenzyme activities were measured. RESULTS: Mean concentration of
TNFalpha increased over 2 fold in CHF patients (12.54 +/- 11.69 pg/ml compared
with 6.0 +/- 6.58 pg/ml in controls). The highest level of TNFalpha was observed
in patients with the final stage of the disease (NHYA IV subgroup), according to
the New York Heart Association classification. tADA activity was significantly
lower in CHF patients compared with controls (19.29 +/- 9.73 and 24.3 +/- 6.01
U/L, respectively). ADA2 activity markedly decreased in CHF patients and showed a
direct correlation with tADA (r = 0.641, P = 0001). In addition, the lowest
levels of tADA and ADA2 activities were observed in patients from the 4(th)
quartile of NYHA classification. CONCLUSION: Adenosine deaminase activity is
reduced in CHF patients to give rise to the concentration of adenosine, thereby
attenuating pathologic consequences of CHF. Therefore, it is concluded that ADA
activity is of paramount importance in pathophysiology of heart failure and might
be used for diagnostic purposes or treatment targets.
PMID- 26417244
TI - On-site cellulase production by Trichoderma reesei 3EMS35 mutant and same vessel
saccharification and fermentation of acid treated wheat straw for ethanol
production.
AB - Bioethanol production from lignocellulosic raw materials involves process steps
like pre-treatment, enzymatic hydrolysis, fermentation and distillation. In this
study, wheat straw was explored as feedstock for on-site cellulase production by
T. reesei 3EMS35 mutant, and as a substrate for second generation bioethanol
production from baker yeast. Scanning electron microscopy (SEM) and X-ray
diffractography (XRD) of untreated wheat straw (UWS) and acid treated wheat straw
(TWS) were done to understand the structural organization and changes in the
cellulase accessibility and reactivity. The effect of delignification and
structural modification for on-site cellulase enzyme production was comparably
studied. The efficiency of crude cellulase enzyme for digestion of UWS and TWS
and then production of ethanol from TWS was studied using same-vessel
saccharification and fermentation (SVSF) technique, both in shaking flasks as
well as in fermenters. Two different methods of operation were tested, i.e. the
UWSEnz method, where UWS was used for on-site enzyme production, and TWSEnz
method where TWS was applied as substrate for cellullase production. Results
obtained showed structural modifications in cellulose of TWS due to
delignification, removal of wax and change of crystallinity. UWS was better
substrate than TWS for cellulase production due to the fact that lignin did not
hinder the enzyme production by fungus but acted as a booster. On-site cellulase
enzyme produced by T. reesei 3EMS35 mutant hydrolyzed most of cellulose (91 %) in
TWS within first 24 hrs. Shake flasks experiments showed that ethanol titers and
yields with UWSEnz were 2.9 times higher compared to those obtained with TWSEnz
method respectively. Comparatively, titer of ethanol in shake flask experiments
was 10 % higher than this obtained in 3 L fermenter with UWSEnz. Outcomes from
this investigation clearly demonstrated the potential of on-site cellulase enzyme
production and SVSF for ethanol production from wheat straw.
PMID- 26417243
TI - Balance of inflammatory pathways and interplay of immune cells in the liver
during homeostasis and injury.
AB - Multiple potentially harmful stimuli challenge the liver, the chief metabolic and
detoxifying organ of the human body. Due to its central anatomical location,
continuous blood flow from the gastrointestinal tract through the hepatic
sinusoids allows the metabolically active hepatocytes, the non-parenchymal cells
and the various immune cell populations residing and patrolling in the liver to
interact with antigens and microbiological components coming from the intestine.
Cytokines are key mediators within the complex interplay of intrahepatic immune
cells and hepatocytes, because they can activate effector functions of immune
cells as well as hepatocytic intracellular signaling pathways controlling
cellular homeostasis. Kupffer cells and liver-infiltrating monocyte-derived
macrophages are primary sources of cytokines such as tumor necrosis factor (TNF).
The liver is also enriched in natural killer (NK) and natural killer T (NKT)
cells, which fulfill functions in pathogen defense, T cell recruitment and
modulation of fibrogenic responses. TNF can activate specific intracellular
pathways in hepatocytes that influence cell fate in different manners, e.g. pro
apoptotic signals via the caspase cascade, but also survival pathways, namely the
nuclear factor (NF)-kappaB pathway. NF-kappaB regulates important functions in
liver physiology and pathology. The exact dissection of the contribution of
recruited and resident immune cells, their soluble cytokine and chemokine
mediators and the intracellular hepatocytic response in liver homeostasis and
injury could potentially identify novel targets for the treatment of acute and
chronic liver disease, liver fibrosis or cirrhosis.
PMID- 26417241
TI - Particles from preformed polymers as carriers for drug delivery.
AB - Biodegradable and biocompatible polymers are widely used for the encapsulation of
drug molecules. Various particulate carriers with different sizes and
characteristics have been prepared by miscellaneous techniques. In this review,
we reported the commonly used preformed polymer based techniques for the
preparation of micro and nano-structured materials intended for drug
encapsulation. A description of polymer-solvent interaction was provided. The
most widely used polymers were reported and described and their related research
studies were mentioned. Moreover, principles of each technique and its crucial
operating conditions were described and discussed. Recent applications of all the
reported techniques in drug delivery were also reviewed.
PMID- 26417245
TI - Thymoquinone and curcumin attenuate gentamicin-induced renal oxidative stress,
inflammation and apoptosis in rats.
AB - The present study was aimed to investigate the possible protective effects of
thymoquinone (TQ) and curcumin (Cur) on gentamicin (GM)-induced nephrotoxicity in
rats. Rats were divided into four groups as follows: group 1 received normal
saline and served as normal controls, group 2 received GM only, group 3
concurrently received GM and TQ and group 4 concurrently received GM and Cur. At
day 21, rats were sacrificed and samples were collected for assaying serum tumor
necrosis factor alpha (TNF-alpha), urea and creatinine levels, and renal lipid
peroxidaion, glutathione (GSH) content as well as glutathione peroxidase (GPx)
and superoxide dismutase (SOD) activities. In addition, kidneys were collected
for histopathological examination and immunohistochemical determination of the
antiapoptotic protein, B-cell lymphoma 2 (Bcl-2). The biochemical results showed
that GM-induced nephrotoxicity was associated with a significant increase in
serum TNF-alpha, urea and creatinine as well as renal lipid peroxidation. On the
other hand, renal GSH content and GPx and SOD activities were significantly
declined. Concomitant administration of either TQ or Cur efficiently alleviated
the altered biochemical and histopathological features. In conclusion, both TQ
and Cur showed more or less similar marked renoprotective effect against GM
induced nephrotoxicity through their antioxidant, anti-inflammatory and anti
apoptotic efficacies.
PMID- 26417247
TI - Hypochoeris radicata attenuates LPS-induced inflammation by suppressing p38, ERK,
and JNK phosphorylation in RAW 264.7 macrophages.
AB - Hypochoeris radicata, an invasive plant species, is a large and growing threat to
ecosystem integrity on Jeju Island, a UNESCO World Heritage site. Therefore,
research into the utilization of H. radicata is important and urgently required
in order to solve this invasive plant problem in Jeju Island. The broader aim of
our research is to elucidate the biological activities of H. radicata, which
would facilitate the conversion of this invasive species into high value-added
products. The present study was undertaken to identify the pharmacological
effects of H. radicata flower on the production of inflammatory mediators in
macrophages. The results indicate that the ethyl acetate fraction of H. radicata
extract (HRF-EA) inhibited the production of pro-inflammatory molecules such as
NO, iNOS, PGE2, and COX-2, and cytokines such as TNF-alpha, IL-1beta, and IL-6 in
LPS-stimulated RAW 264.7 cells. Furthermore, the phosphorylation of MAPKs such as
p38, ERK, and JNK was suppressed by HRF-EA in a concentration-dependent manner.
In addition, through HPLC and UPLC fingerprinting, luteolins were also identified
and quantified as extract constituents. On the basis of these results, we suggest
that H. radicata may be considered possible anti-inflammatory candidates for
pharmaceutical and/or cosmetic applications.
PMID- 26417248
TI - Immunomodulatory potential of a bioactive fraction from the leaves of
Phyllostachys bambusoides (bamboo) in BALB/c mice.
AB - In order to evaluate the role of ethyl acetate fraction (PB-EtAC) obtained from
the Phyllostachys bambusoides leaves in the modulation of immune responses,
detailed studies were carried out using a panel of in vivo assays. Oral
administration of PB-EtAC (50-200 mg/Kg) stimulated the IgM and IgG titre
expressed in the form of haemagglutination antibody (HA) titre. Further, it
elicited a dose related increase in the delayed type hypersensitivity reaction
(DTH) after 24 and 48 h in BALB/c mice. Besides augmenting the humoral and cell
mediated immune response, the concentration of cytokines (IFN-gamma, IL-2, and IL
4) in serum with respect to T cell interactions also increased significantly. It
also induced macrophage phagocytosis, and nitric oxide (NO) production which
resulted in a high degree of protection against Candida albicans and carbon
clearance. Moreover, the enhancement in CD4 and CD8 cell populations as revealed
by flow cytometry. Taken together this in vivo and ex vivo preclinical data, our
results suggested that PB-EtAC acts as an effective immunostimulator eliciting
both Th1 and Th2 immune responses. We are reporting first time the
immunostimulatory potential of P. bambusoides and it might be regarded as a
biological response modifier.
PMID- 26417246
TI - Select a suitable treatment strategy for Crohn's disease: step-up or top-down.
AB - Crohn's Disease (CD) is a chronic immune-mediated disorder with progressive and
destructive course. Current guidelines on the treatment strategy still recommend
a step-up approach with sequential prescription of corticosteroids and
immunosuppressives. However, mounting evidences manifested that top-down therapy
with early administration of anti-TNF or combination of immunosuppressives can
achieve more rapid and higher rate of mucosal healing and has the potential of
modifying the natural course of disease. Therefore, who is suitable to accept and
when to start anti-TNF therapy have attracted the attention of
gastroenterologists. And what benefit/risk can be expected from the two
strategies should be carefully taken into account by clinicians. Age
stratification, special patients, disease location and extension, genetic and
serologic testing are predictors of disease progression and complication and thus
guide a personalized treatment approach in CD. A definition of early CD has been
proposed to select an algorithm for treatment of moderate-to-severe CD with a
suitable strategy. To date mucosal healing has been widely used, the Lemann
score, which assesses the extent and severity of bowel damage at a specific time
point and over time, and is a new disability index for patients with CD, will be
considered as a new endpoint for future studies of treatment strategies. Besides
medicines of the two strategies, surgery, vaccine, Leukocytapheresis and stem
cell therapy are all effective therapeutic approaches which lead to another
thinking about what should they be putted in the conditional pyramid. However, we
are trying to answer these questions.
PMID- 26417249
TI - Detrimental effects of bisphenol A on development and functions of the male
reproductive system in experimental rats.
AB - Bisphenol A (BPA) is widely used in manufacturing industries. It is commonly
detected in the environment and was reported to exert oestrogenic effects which
may be harmful to the reproductive system. The present study was carried out to
observe the effects of oral administration of BPA on the development of the
reproductive organs and plasma sex hormone levels in prepubertal male Sprague
Dawley (SD) rats. Prepubertal male SD rats (n=8 in each group) were administered
BPA in the doses of 1, 5, 10 and 100 mg/kg BW (body weight) via oral gavage for a
period of 6 weeks. The control animals received the vehicle for BPA (Tween 80 in
distilled water). Following 6 weeks of BPA exposure, the rats exhibited less
evidence of spermatogenesis. There was seminiferous epithelial damage which
included disruption of intercellular junctions and sloughing of germ cells into
the seminiferous tubular lumen. Furthermore, the lumina of the seminiferous
tubules and the epididymis of these animals were filled with immature germ cells
and cellular debris. This damage may lead to the significant reduction in the
seminiferous tubular diameter in BPA-treated animals. These findings were
associated with the significant lower plasma testosterone and 17beta-oestradiol
levels. There was no significant difference between the body weight gain, the
absolute as well as relative testis weight or epididymal weight of BPA-treated
animals when compared to the control animals. The findings provided further
evidence of the detrimental effects of BPA on the male reproductive system.
PMID- 26417250
TI - Response of liver antioxidant defense system to acute and chronic physical and
psychological stresses in male rats.
AB - The aim of this study was to evaluate the effect of acute and chronic physical
and psychological stressors on the induction of oxidative stress in male rat
liver. Male Wistar rats were randomly divided into 3 groups as following:
control, physical and psychological stress groups. Stress was induced by
communication box for one (acute), fifteen and thirty (chronic) days. Once
stressor periods ended, rats were anesthetized and their liver dissected out for
later assessments. Exposure to physical stress enhanced liver superoxide
dismutase (SOD) (19.44 %) and glutathione S-transferase (GST) (21.84 %)
activities and decreased glutathione (GSH) (30.03 %) level on the 1(st) day
(p<0.05). SOD (24.13 and 18.43 %) and GST (27.77 and 21.27 %) activities were
significantly increased, while catalase activity (29.74 and 24.41 %) and GSH
level (35.05 and 31.05 %) were decreased in psychological stress group after 1
and 15 days (p<0.01 and p<0.05) compared to the 1(st) day value in control group,
respectively. Psychological stress induced an increase in liver malondialdehyde
(MDA) (46 %) and plasma corticosterone (36 %) levels on the 1(st) day (p<0.05).
However, all parameters returned to their basal value after 30 days of stress.
The results suggest that exposure to acute physical and psychological stressors
induce the production of reactive oxygen species and oxidative stress in rat
liver due to GSH depletion and the decreased catalase activity. The elevation of
lipid peroxidation and corticosterone level in acute psychological stress may
lead to more profound oxidative damage than acute physical stress. Moreover, cell
protection in hepatic tissue of chronically stressed rats is indicative of
possible late adaptation of the animals to stress.
PMID- 26417251
TI - Influence of environmental variability on phylogenetic diversity and trait
diversity within Calligonum communities.
AB - Since phylogenetic data provide the evolutionary history of the species and
traits are the result of adaptation to the environmental conditions, joint
analysis of these two aspects and ecological data may illuminate that how
ecological processes affect the evolution of species and assembly of communities.
In this study, we compared the community structure of sibling communities in
order to illuminate the influence of environmental variability. We chose
different Calligonum communities as research subjects which grow in active sand
dunes and stabilized sand fields. Our results show that species which co-occurred
in C. rubicundum community have greater phylogenetic evenness compared to species
in other communities where co-occurring plants had similar traits. Soil
variability might legitimately explain this result. Based on the similarity
between the pattern of trait diversity and the pattern of phylogenetic diversity,
we inferred that the evolution of traits is conservative and species of all but
C. rubicundum communities are under more intense selection pressure.
PMID- 26417253
TI - Vascular loop in the cerebellopontine angle causing pulsatile tinnitus and
headache: a case report.
AB - Tinnitus is a common disorder, it can be classified as pulsatile and non
pulsatile or objective and subjective. Pulsatile tinnitus is less common than non
pulsatile and can be due to vascular tumour such as glomus or vascular
abnormality. We presented an interesting case of a 30 year-old Malay lady with a
two-year history of pulsatile tinnitus which was worsening in three months
duration. It was associated with intermittent headache. Clinical examination and
tuning fork test were unremarkable. Apart from mild hearing loss at high
frequency on the left ear, the pure tone audiogram (PTA) was otherwise normal. In
view of the patient's young age with no risk factor for high frequency loss, a
magnetic resonance imaging (MRI) was performed to look for any abnormality in the
cerebellopontine angle. It revealed a single vessel looping around the left
vestibulocochlear and facial nerves at the cisternal portion, likely a branch of
the anteroinferior cerebellar artery (AICA). Literature review on the
pathophysiology and treatment option in this condition is discussed.
PMID- 26417252
TI - Autophagy and radiosensitization in cancer.
AB - Autophagy is a natural self-degradative process by which cells eliminate
misfolded proteins and damaged organelles. Autophagy has been shown to have
multiple functions in tumor cells that may be dependent on the tumor type and the
treatment conditions. Autophagy can have a cytoprotective role and be thought of
as a survival mechanism or be cytotoxic in nature and mediate cell death.
Radiation, one of the primary treatments for many different types of cancer,
almost uniformly promotes autophagy in tumor cells. While autophagy produced in
response to radiation is often considered to be cytoprotective, radiation-induced
autophagy has also been shown to mediate susceptibility to radiation. This review
addresses the complexity of autophagy in response to radiation treatment in three
different cancer models, specifically lung cancer, breast cancer and
glioblastoma. A deeper understanding of the different roles played by autophagy
in response to radiation should facilitate the development of approaches for
enhancing the therapeutic utility of radiation by providing strategies for
combination treatment with unique radiosensitizers as well as preventing the
initiation of strategies which are likely to attenuate the effectiveness of
radiation therapy.
PMID- 26417254
TI - Analysis of concentration-dependent effects of copper and PCB on different
Chattonella spp. microalgae (raphidophyceae) cultivated in artificial seawater
medium.
AB - In the present study, the effect on the chlorophyll a and the total protein
content as well as the Chattonella spp. cell viability were examined after
concentration-dependent exposure to CuCl2 and Aroclor 1242. The comparison
between various raphidophyte strains provides an insight into the different
susceptibilities to contaminants of Chattonella subsalsa (CSNAV-1), C. marina
var. marina (CMCV-1) and C. marina var. ovata (COPV-2). The microalgae were
cultivated in artificial seawater medium. Exponentially growing microalgae (8-10
days in culture) were used for exposure experiments. We observed in all three
raphidophyte species cytotoxicity-mediated modifications beginning at
concentrations of 150 and 200 uM of the heavy metal copper after 24 hours
exposure. But interestingly, the three strains exhibited only slight differences
in their susceptibility to CuCl2. C. subsalsa and C. marina var. marina cells
were first affected at the chlorophyll a level and in cell viability. The total
protein amount was reduced significantly only after exposure to 300 uM of CuCl2.
However, C. marina var. ovata microalgae showed similar reduction curves for all
three analysed cytotoxicity endpoints after heavy metal exposure. On the other
hand, after Aroclor 1242 incubation the cytotoxic modification pattern indicated
clearly the different susceptibilities of the three raphidophyte strains. C.
subsalsa cells noticeably exhibited a decrease in the analysed pigment amount (30
20 % compared to that of the control) already after 0.007 mg/L PCB exposure. In
contrast, cell viability and total protein content were slightly reduced and fell
below the 50 % threshold after 0.7 and 3.3 mg/L of Aroclor 1242, respectively.
Interestingly, C. marina var. ovata showed almost no cytotoxic modification
caused by the PCB mixture. Only the concentration of 0.7 mg/L Aroclor 1242
clearly affected the cell viability. As opposed to that we observed a
concentration-dependent decrease of cell viability and chlorophyll a amount in
CMCV-1 microalgae. These observations confirmed that the susceptibility of the
raphidophytes strains CSNAV-1, CMCV-1 and COPV-2 is contaminant-dependent. We
showed differences even between two variants of Chattonella (Chattonella marina
var. marina and C. marina var. ovata). Furthermore, we were able to show the
different mode of action of two common pollutants by simple cytotoxic parameters
like total protein and chlorophyll a content as well as by cell counting
analysis.
PMID- 26417255
TI - Conformational instability of human prion protein upon residue modification: a
molecular dynamics simulation study.
AB - Technical strategies like amino acid substitution and residue modification have
been widely used to characterize the importance of key amino acids and the role
that each residue plays in the structural and functional properties of protein
molecules. However, there is no systematic approach to assess the impact of the
substituted/modified amino acids on the conformational dynamics of proteins. In
this investigation to clarify the effects of residue modifications on the
structural dynamics of human prion protein (PrP), a comparative molecular
dynamics simulation study on the native and the amino acid-substituted analog at
position 208 of PrP has been performed. It is believed that Arginine to Histidine
mutation at position 208 is responsible for the structural transition of the
native form of human prion protein to the pathogenic isoform causing Creutzfeldt
Jakob disease (CJD). So, three 10 ns molecular dynamics simulations on three
model constructs have been performed. Simulation results indicated considerable
differences of conformational fluctuations for Alanine substituted construct
(PrPALA) and the analog form (PrPSB) comprising the neutralized state of the
Arginine residue at position 208 of the human prion protein. According to our
data, substitution of the Arginine residue by the uncharged state of this residue
induces some reversible structural alterations in the intrinsically flexible loop
area including residues 167-171 of PrP. Thus, deprotonation of Arg(208) is a weak
perturbation to the structural fluctuations of the protein backbone and the
resulting construct behaves almost identical as its native form. Otherwise,
Alanine substitution at position 208 imposed an irreversible impact on the
secondary and tertiary structure of the protein, which leads to conformational
instabilities in the remote hot region comprising residues 190-195 of the C
terminal part of helix 2. Based on the results, it could be deduced that the
observed conformational transitions upon Arg(208) to His point mutation, which is
the main reason for CJD, may be mainly related to the structural instabilities
due to the induced-conformational changes that caused alterations in
local/spatial arrangements of the force distributions in the backbone of the
human prion protein.
PMID- 26417256
TI - Pomegranate peel attenuates hyperglycemic effects of alloxan-induced diabetic
rats.
PMID- 26417257
TI - Design, synthesis and anticonvulsant activity of some new 6,8-halo-substituted-2h
[1,2,4]triazino[5,6-b]indole-3(5h)-one/-thione and 6,8-halo-substituted 5-methyl
2h-[1,2,4]triazino[5,6-b]indol-3(5h)-one/-thione.
AB - A new series of 6,8-halo-substituted-2H-[1,2,4]triazino[5,6-b]indole-3(5H)-one/
thione and 6,8-halo-substituted 5-methyl-2H-[1,2,4]triazino[5,6-b]indol-3(5H)
one/-thione (5a-5l) were designed and synthesized keeping in view of the
structural requirement of pharmacophore. The above compounds were characterized
by thin layer chromatography and spectral analysis. Anticonvulsant activity of
the synthesized compounds was evaluated by the maximal electroshock (MES) test.
Neurotoxicity and CNS depressant effects were evaluated by the rotarod motor
impairment and Porsolt's force swim tests, respectively. A computational study
was carried out, for calculation of pharmacophore pattern, prediction of
pharmacokinetic properties and toxicity properties. The above study revealed that
the compounds 8-chloro-2H-[1,2,4]triazino[5,6-b]indol-3(5H)-one (5e), 6,8-dibromo
2H-[1,2,4]triazino[5,6-b]indol-3(5H)-one (5i) and 6,8-dibromo-5-methyl-2H
[1,2,4]triazino[5,6-b]indol-3(5H)-one (5k) possess excellent anticonvulsant
activity in the series with little CNS depressant effect and no neurotoxicity as
compared to standard drugs phenytoin and carbamazepine.
PMID- 26417258
TI - Level set method for segmentation of infrared breast thermograms.
AB - Breast thermography is a physiological test that provides information based on
the temperature changes in breast. It records the temperature distribution of a
body using the infrared radiation emitted by the surface of that body.
Precancerous tissue and the area around a cancerous tumor have higher temperature
due to angiogenesis, and higher chemical and blood vessel activity than a normal
breast; hence breast thermography has potential to detect early abnormal changes
in breast tissues. It can detect the first sign of forming up cancer before
mammography can detect. The thermal information can be shown in a pseudo colored
image where each color represents a specific range of temperature. Various
methods can be applied to extract hot regions for detecting suspected regions of
interests in the breast infrared images and potentially suspicious tissues. Image
segmentation techniques can play an important role to segment and extract these
regions in the breast infrared images. Shape, size and borders of the hottest
regions of the images can help to determine features which are used to detect
abnormalities. In this paper, three image segmentation methods: k-means, fuzzy c
means and level set are discussed and compared. These three methods are tested
for different cases such as fibrocystic, inflammatory cancer cases. The hottest
regions of thermal breast images in all cases are extracted and compared to the
original images. According to the results, level set method is a more accurate
approach and has potential to extract almost exact shape of tumors.
PMID- 26417259
TI - Imprinting genes associated with endometriosis.
AB - PURPOSE: Much work has been carried out to investigate the genetic and epigenetic
basis of endometriosis and proposed that endometriosis has been described as an
epigenetic disease. The purpose of this study was to extract the imprinting genes
that are associated with endometriosis development. METHODS: The information on
the imprinting genes can be accessed publicly from a web-based interface at
http://www.geneimprint.com/site/genes-by-species. RESULTS: In the current
version, the database contains 150 human imprinted genes derived from the
literature. We searched gene functions and their roles in particular biological
processes or events, such as development and pathogenesis of endometriosis. From
the genomic imprinting database, we picked 10 genes that were highly associated
with female reproduction; prominent among them were paternally expressed genes
(DIRAS3, BMP8B, CYP1B1, ZFAT, IGF2, MIMT1, or MIR296) and maternally expressed
genes (DVL1, FGFRL1, or CDKN1C). These imprinted genes may be associated with
reproductive biology such as endometriosis, pregnancy loss, decidualization
process and preeclampsia. DISCUSSION: This study supports the possibility that
aberrant epigenetic dysregulation of specific imprinting genes may contribute to
endometriosis predisposition.
PMID- 26417260
TI - Nanoencapsulation for drug delivery.
AB - Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very
promising approach for development of nanomedicine. Modern drug encapsulation
methods allow efficient loading of drug molecules inside the NCs thereby reducing
systemic toxicity associated with drugs. Targeting of NCs can enhance the
accumulation of nanonencapsulated drug at the diseased site. This article
focussed on the synthesis methods, drug loading, drug release mechanism and
cellular response of nanoencapsulated drugs on liposomes, micelles, carbon
nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have
been highlighted in the field of nanotechnology.
PMID- 26417261
TI - In vitro study of parasite elimination and endothelial protection by curcumin:
adjunctive therapy for cerebral malaria.
AB - Plasmodium falciparum infection can abruptly progress to severe malaria and
cerebral malaria. Despite the current efficiency of antimalarial drugs in killing
parasites, no specific effective treatment has been found for cerebral malaria.
Thus, a new strategy targeting both parasite elimination and endothelial cell
protection is urgently needed in this field. In this study, we determined whether
curcumin, which has blood-brain permeability, antioxidative activity and/or
immunomodulation property, provided a potential effect on both parasite
elimination and endothelial protection. Murine brain microvascular endothelial
cells (bEnd.3; ATCC) were cocultured with Plasmodium falciparum-infected red
blood cells (Pf-IRBC), peripheral blood mononuclear cell (PBMC) and platelets.
Apoptosis of endothelial cells was demonstrated by annexin V staining.
Interestingly, curcumin exhibited high efficiency of antimalarial activity (IC50
~10 uM) and decreased bEnd.3 apoptosis down to 60.0 % and 79.6 % upon pre
treatment and co-treatment, respectively, with Pf-IRBC, platelets and PBMC. Our
findings open up a high feasibility of applying curcumin as a potential
adjunctive compound for cerebral malaria treatment in the future.
PMID- 26417263
TI - Antioxidant and antiulcer potential of aqueous leaf extract of Kigelia africana
against ethanol-induced ulcer in rats.
AB - Ethnobotanical claims regarding Kigelia africana reported antiulcer properties as
part of its medicinal application. In this work, aqueous leaf extract from K.
africana was investigated for its phytochemical constituents and antiulcer
potential against ethanol-induced ulcer in rats. The participation of oxidative
stress on ethanol-induced ulcer and the potential protective antioxidant activity
of K. africana extracts were investigated by determining vitamin C and
thiobarbituric acid reactive species (TBARS) contents in the gastric mucosa of
rats. The HPLC analysis showed the presence of gallic acid, chlorogenic acid,
caffeic acid and also the flavonoids rutin, quercetin and kaempferol in the
aqueous plant extract. Oral treatment with K. africana extract (1.75; 3.5; 7 and
14 mg/kg) one hour after ulcer induction with ethanol decreased in a dose
dependent manner the ulcer index. Ethanol increased significantly stomachal TBARS
levels and decreased vitamin C content when compared to the control animals. K.
africana blunted the ethanol-induced oxidative stress and restored vitamin C
content to the control levels. The present results indicate that the aqueous leaf
extract from K. africana possesses antiulcer potential. The presence of
flavonoids in plant extract suggests that its antiulcerogenic potential is
associated with antioxidant activity. Of particular therapeutic potential, K.
africana was effective against ethanol even after the induction of ulcer,
indicating that it can have protective and curative effects against gastric
lesion.
PMID- 26417262
TI - Mycoplasmas and cancer: focus on nucleoside metabolism.
AB - The standard of care for patients suffering cancer often includes treatment with
nucleoside analogues (NAs). NAs are internalized by cell-specific
nucleobase/nucleoside transporters and, after enzymatic activation (often one or
more phosphorylation steps), interfere with cellular nucleo(s)(t)ide metabolism
and DNA/RNA synthesis. Therefore, their efficacy is highly dependent on the
expression and activity of nucleo(s)(t)ide-metabolizing enzymes, and alterations
thereof (e.g. by down/upregulated expression or mutations) may change the
susceptibility to NA-based therapy and/or confer drug resistance. Apart from host
cell factors, several other variables including microbial presence may determine
the metabolome (i.e. metabolite concentrations) of human tissues. Studying the
diversity of microorganisms that are associated with the human body has already
provided new insights in several diseases (e.g. diabetes and inflammatory bowel
disease) and the metabolic exchange between tissues and their specific microbiota
was found to affect the bioavailability and toxicity of certain anticancer drugs,
including NAs. Several studies report a preferential colonization of tumor
tissues with some mycoplasma species (mostly Mycoplasma hyorhinis). These
prokaryotes are also a common source of cell culture contamination and alter the
cytostatic activity of some NAs in vitro due to the expression of nucleoside
catabolizing enzymes. Mycoplasma infection may therefore bias experimental work
with NAs, and their presence in the tumor microenvironment could be of
significance when optimizing nucleoside-based cancer treatment.
PMID- 26417264
TI - Encapsulation of catechin and epicatechin on BSA NPS improved their stability and
antioxidant potential.
AB - Nanoencapsulation of antioxidant molecules on protein nanoparticles (NPs) could
be an advanced approach for providing stable, better food nutraceuticals and
anticancer drugs. The bioavailability and stability of catechin (CAT) and
epicatechin (ECAT) were very poor. In the present study, the CAT and ECAT were
loaded on bovine serum albumin (BSA) NPs following desolvation method. The
transmission electron microscope (TEM) and atomic force microscope (AFM) recorded
size of CAT-BSA NPs and ECAT-BSA NPs were 45 +/- 5 nm and 48 +/- 5 nm
respectively. The encapsulation efficiency of CAT and ECAT on BSA NPs was found
to be 60.5 and 54.5 % respectively. CAT-BSA NPs and ECAT-BSA NPs show slow and
sustained in vitro release. The CAT-BSA NPs and ECAT-BSA NPs were stable in
solution at various temperatures 37 degrees C, 47 degrees C and 57 degrees C.
DPPH assay revealed that CAT and ECAT maintained their functional activity even
after encapsulation on BSA NPs. Furthermore, the efficacy of CAT-BSA NPs and ECAT
BSA NPs determined against A549 cell lines was found to be improved. CAT and ECAT
aptly encapsulated in BSA NPs, showed satisfactory sustained release, maintained
antioxidant potential and found improved efficacy. This has thus suggested their
more effective use in food and nutraceuticals as well as in medical field.
PMID- 26417266
TI - EST sequencing and gene expression profiling in Scutellaria baicalensis.
AB - Scutellaria baicalensis is an important medicinal plant, but few genomic
resources are available for this species, as well as for other non-model plants.
One of the major new directions in genome research is to discover the full
spectrum of genes transcribed from the whole genome. Here, we report extensive
transcriptome data of the early growth stage of S. baicalensis. This
transcriptome consensus sequence was constructed by de novo assembly of shotgun
sequencing data, obtained using multiple next-generation DNA sequencing (NGS)
platforms (Roche/454 GS_FLX+ and Illumina/Solexa HiSeq2000). We show that this
new approach to obtain extensive mRNA is an efficient strategy for genome-wide
transcriptome analysis. We obtained 1,226,938 and 161,417,646 reads using the
GS_FLX and the Illumina/Solexa HiSeq2000, respectively. De novo assembly of the
high-quality GS_FLX and Illumina reads (95 % and 75 %) resulted in more than 82
Mb of mRNA consensus sequence, which we assembled into 51,188 contigs, with at
least 500 bp per contig. Of these contigs, 39,581 contained known genes, as
determined by BLASTX searches against non-redundant NCBI database. Of these,
20,498 different genes were expressed during the early growth stage of S.
baicalensis. We have made the expressed sequences available on a public database.
Our results demonstrate the utility of combining NGS technologies as a basis for
the development of genomic tools in non-model, medicinal plant species. Knowledge
of all described genes and quantitation of the expressed genes, including the
transcription factors involved, will be useful in studies of the biology of S.
baicalensis gene regulation.
PMID- 26417267
TI - Polyacrylamide hydrogel encapsulated E. coli expressing metal-sensing green
fluorescent protein as a potential tool for copper ion determination.
AB - A simple, inexpensive and field applicable metal determination system would be a
powerful tool for the efficient control of metal ion contamination in various
sources e.g. drinking-water, water reservoir and waste discharges. In this study,
we developed a cell-based metal sensor for specific and real-time detection of
copper ions. E. coli expressing metal-sensing green fluorescent protein
(designated as TG1/(CG)6GFP and TG1/H6CdBP4GFP) were constructed and served as a
metal analytical system. Copper ions were found to exert a fluorescence quenching
effect, while zinc and cadmium ions caused minor fluorescence enhancement in the
engineered bacterial suspension. To construct a user-friendly and reagentless
metal detection system, TG1/H6CdBP4GFP and TG1/(CG)6GFP were encapsulated in
polyacrylamide hydrogels that were subsequently immobilized on an optical fiber
equipped with a fluorescence detection module. The sensor could be applied to
measure metal ions by simply dipping the encapsulated bacteria into a metal
solution and monitoring fluorescence changes in real time as a function of the
metal concentration in solution. The sensor system demonstrated high specificity
toward copper ions. The fluorescence intensities of the encapsulated TG1/(CG)6GFP
and TG1/H6CdBP4GFP were quenched by approximately 70 % and 80 % by a high-dose of
copper ions (50 mM), respectively. The level of fluorescence quenching exhibited
a direct correlation with the copper concentration, with a linear correlation
coefficient (r) of 0.99. The cell-based metal sensor was able to efficiently
monitor copper concentrations ranging between 5 M and 50 mM, encompassing the
maximum allowed copper contamination in drinking water (31.15 M) established by
the WHO. Furthermore, the cell-based metal sensor could undergo prolonged storage
for at least 2 weeks without significantly influencing the copper sensitivity.
PMID- 26417265
TI - Cytochrome P450 enzyme mediated herbal drug interactions (Part 1).
AB - It is well recognized that herbal supplements or herbal medicines are now
commonly used. As many patients taking prescription medications are concomitantly
using herbal supplements, there is considerable risk for adverse herbal drug
interactions. Such interactions can enhance the risk for an individual patient,
especially with regard to drugs with a narrow therapeutic index such as warfarin,
cyclosporine A and digoxin. Herbal drug interactions can alter pharmacokinetic
or/and pharmacodynamic properties of administered drugs. The most common
pharmacokinetic interactions usually involve either the inhibition or induction
of the metabolism of drugs catalyzed by the important enzymes, cytochrome P450
(CYP). The aim of the present article is to provide an updated review of
clinically relevant metabolic CYP-mediated drug interactions between selected
herbal supplements and prescription drugs. The commonly used herbal supplements
selected include Echinacea, Ginkgo biloba, garlic, St. John's wort, goldenseal,
and milk thistle. To date, several significant herbal drug interactions have
their origins in the alteration of CYP enzyme activity by various phytochemicals.
Numerous herbal drug interactions have been reported. Although the significance
of many interactions is uncertain but several interactions, especially those with
St. John's wort, may have critical clinical consequences. St. John's wort is a
source of hyperforin, an active ingredient that has a strong affinity for the
pregnane xenobiotic receptor (PXR). As a PXR ligand, hyperforin promotes
expression of CYP3A4 enzymes in the small intestine and liver. This in turn
causes induction of CYP3A4 and can reduce the oral bioavailability of many drugs
making them less effective. The available evidence indicates that, at commonly
recommended doses, other selected herbs including Echinacea, Ginkgo biloba,
garlic, goldenseal and milk thistle do not act as potent or moderate inhibitors
or inducers of CYP enzymes. A good knowledge of the mechanisms of herbal drug
interactions is necessary for assessing and minimizing clinical risks. These
processes help prediction of interactions between herbal supplements and
prescription drugs. Healthcare professionals should remain vigilant for potential
interactions between herbal supplements/medicines and prescription drugs,
especially for drugs with a narrow therapeutic index are used.
PMID- 26417269
TI - Antifungal potential of essential oil and ethanol extracts of Lonicera japonica
Thunb. against dermatophytes.
AB - The antifungal potential of essential oil and ethanolic leaf extracts of Lonicera
japonica Thunb. was evaluated for controlling the growth of dermatophytes. The
oil (1,000 ppm) and extracts (1,500 ppm) of L. japonica revealed 55.1-70.3 % and
40.1-65.5 % antidermatophytic effect against Microsporum canis KCTC 6348, 6349,
6591, Trichophyton rubrum KCTC 6345, 6352, 6375, Trichophyton mentagrophytes KCTC
6077 and 6085, respectively, along with their respective minimum inhibitory
concentrations ranging from 62.5-500 and 125-1,000 ug/ml. Also, the oil had
strong detrimental effect on spore germination of all the tested dermatophytes as
well as concentration and time-dependent kinetic inhibition of M. canis KCTC
6348. The results demonstrated that L. japonica oil and extracts could be
potential sources of natural fungicides to protect human and animals from fungal
infections.
PMID- 26417268
TI - Arylesterase activity is associated with antioxidant intake and paraoxonase-1
(PON1) gene methylation in metabolic syndrome patients following an energy
restricted diet.
AB - The arylesterase (ARE) activity linked to the paraoxonase-1 (PON1) gene is known
to protect lipoproteins from oxidation and provide defense against metabolic
syndrome (MetS) and cardiovascular diseases. The epigenetic regulation of
enzymatic activities is gaining importance nowadays. This research aimed to
assess the potential relationships between the ARE activity with the methylation
levels of the PON1 gene transcriptional regulatory region, anthropometrics,
biochemical markers and antioxidant dietary components. Forty-seven subjects (47
+/- 10 y.o; BMI 36.2 +/- 3.8 kg/m(2); 46.8 % female) with MetS features, who
followed a six-month energy-restricted dietary weight-loss intervention, were
included in this study (www.clinicaltrials.gov; NCT01087086). Anthropometric,
biochemical, enzymatic and dietary data were assessed using validated procedures.
PON1 transcriptional regulatory region methylation was analyzed by a microarray
technical approach. Volunteers reduced ARE activity in parallel with body weight
(p = 0.005), BMI (p = 0.006), total fat mass (p = 0.020), diastolic blood
pressure (p = 0.018), mean blood pressure (p = 0.022) and triglycerides (p =
0.014). Methylation levels of some CpG sites of the PON1 gene correlated
negatively with ARE activity (p < 0.05). Interestingly, dietary vitamin C (p =
0.001), tocopherols (p = 0.009) and lycopene (p = 0.038) were positively
associated with ARE activity and showed an inverse correlation (p = 0.004, p =
0.029 and p = 0.021, respectively) with the methylation of some selected CpG
sites of the PON1 gene. In conclusion, ARE activity decreased in parallel with
MetS-related markers associated to the energy restriction, while dietary
antioxidants might enhance the ARE activity by lowering the PON1 gene methylation
in patients with MetS features.
PMID- 26417270
TI - Synthesis, preclinical evaluation and antidepressant activity of 5-substituted
phenyl-3-(thiophen-2-yl)-4, 5-dihydro-1H-pyrazole-1-carbothioamides.
AB - A series of phenyl-3-(thiophen-2-yl)-4, 5-dihydro-1H-pyrazole-1-carbothioamides
(TTa-TTg) were synthesized by the ring closure reaction of phenyl-1-(thiophen-2
yl) prop-2-en-1-ones with thiosemicarbazide in alcoholic basic medium. All the
final derivatives were evaluated for their antidepressant and neurotoxicity
screening. The structures of the compounds were characterized by IR, 1H NMR, 13C
NMR, Mass and elemental analyses. Preclinical evaluation of the compounds were
ascertained by in silico toxicity, blood-brain barrier and human oral absorption
prediction. In this series, 5-(4-hydroxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H
pyrazole-1 carbothioamide (TTg) reduced immobility time 61.17 and 62.05 % in both
force swimming and tail suspension test respectively at 10 mg/kg dose level when
compared to the standard Imipramine without influencing the baseline locomotion.
Moreover it was observed that the titled scaffold possessing electron withdrawing
chlorine atom in the 4(th) position of aromatic ring of the scaffold also showed
good the antidepressant activity. In conclusion, the behavioural investigation
revealed that thiophene based pyrazolines having a carbothioamide tail unit in
the N1 position may be therapeutically useful as potential antidepressant
medications.
PMID- 26417271
TI - DNA damaging and biochemical effects of potassium tetraborate.
AB - Potassium tetraborate (PTB) is a product resulting from the controlled reaction
of potassium hydroxide, water and boric acid (BA). It is used in many areas of
industry such as disinfectant, detergent and treatment of contact lenses. PTB is
one of the boron compounds which is most commonly used in many areas of industry
although very limited information is available concerning its toxicity.
Therefore, in this study, it is aimed to determine genetic and biochemical
effects of PTB in human blood cell cultures (n=4). PTB was added into culture
tubes at various concentrations (0-1280 ug/ml). Micronucleus (MN) and chromosomal
aberration (CA) tests were performed for genotoxic damage influences estimation.
In addition, biochemical parameters (total antioxidant capacity (TAC) and total
oxidative status (TOS) were examined to determine oxidative effects. The results
indicated that all tested concentrations of PTB were found to be non-genotoxic.
In addition, low concentrations (1.25, 2.5 and 5 ug/ml) of PTB caused increases
of TAC levels. Furthermore, all concentrations of PTB were not changed the TOS
levels in cultured human blood cells. Based on these results, in this study it
has been reported for the first time that PTB is not genotoxic and it increases
the antioxidant capacity in human peripheral blood lymphocytes.
PMID- 26417272
TI - Phytochemicals for treatment of diabetes.
AB - Diabetes Mellitus (DM) is one of the most prevalent metabolic disorders
characterized by increased blood glucose levels and improper primary metabolism
resulting from the defects in insulin secretion, insulin action, or both. It is
one of the most common health problems worldwide, and the prevalence of this
disease is rapidly increasing, leading to microvascular (retinopathy, neuropathy
and nephropathy) and macrovascular (heart attack, stroke and peripheral vascular
disease) complications (Umar et al., 2010[18]). The number of individuals with
diabetes is increasing due to population growth, aging, urbanization and
increasing prevalence of obesity and physical inactivity. According to recent
estimates, the greatest absolute increase in the number of patients with diabetes
will be in India and the total number is projected to 79.4 million in 2030. It is
expected that about 366 million are likely to be diabetic by the year 2030
(Rahman and Zaman, 1989[14]). Medicinal plants are the main source of organic
compounds such as polyphenols, tannins, alkaloids, carbohydrates, terpenoids,
steroids and flavonoids. These organic compounds represent a source for the
discovery and development of new types of antidiabetic molecules. Many compounds
isolated from plant sources have been reported to show antidiabetic activity. The
key messages summarize some recent information in the field of antidiabetic
phytochemicals.
PMID- 26417273
TI - A case of suicide attempt with Zolpidem - will Zolpidem show up on standard urine
toxicology screening?
PMID- 26417274
TI - Highlight report: Validation of prognostic genes in lung cancer.
PMID- 26417276
TI - Risks to health professionals from hazardous drugs in Iran: a pilot study of
understanding of healthcare team to occupational exposure to cytotoxics.
AB - Ongoing concerns exist regarding the dangers inherent when handling cytotoxics,
particularly drugs which are in parenteral formulations. On occasions, nurses and
medical doctors have been preparing and administrating these drugs in the open
spaces of wards in the absence of suitable personal protective equipment (PPE)
and safety cabinets. To explore further into the severity of occupational
hazards, we conducted our research in order to evaluate the healthcare's
understanding of occupational exposure to cytotoxics and occurrence of any side
effects. A cross-sectional study using a self-administered questionnaire was
distributed amongst oncology nurses in nine specialized cancer centers in Tehran.
The questionnaire was based on most reputable international guidelines, aiming to
evaluate the attitude, knowledge and safe practices of nurses' handling cytotoxic
drugs. The gathered data and reported side effects were compared between
"oncology/hematology" and "non-oncology" participants. The majority of nurses
from oncology wards were aware of the potential hazards associated with handling
of chemotherapy and reported high levels of compliance with the use of PPE during
reconstitution of antineoplastic agents. Almost all nurses reported the use of a
safety cabinet during preparation, however only 55 % reported that they have
annual medical checkups and 45 % reported having received specialized training.
This work was also to evaluate the experimental procedures as well as cleaning
solutions used to reduce the level exposure. While the level of knowledge about
antineoplastic agents is high among nurses, along with the level of PPE use,
medical surveillance and employee training seems to be lagging behind.
PMID- 26417277
TI - Effects of Khaya senegalensis leaves on performance, carcass traits, hemtological
and biochemical parameters in rabbits.
AB - One of the challenges facing farmers today is to ensure adequate integration of
natural resources into animal feeds. The aim of the present study is to evaluate
the effects of Khaya senegalensis (KS) leaves on the performance of growing male
rabbits, carcass traits and biochemical as well as hematological parameters.
Thirty New Zealand White male growing rabbits were randomly divided into 3 groups
(10 rabbits per group). Group I (control) received standard rabbit diet. Rabbits
in group II and group III were fed standard rabbit diet supplemented with 35 %
and 65 % KS leaves, respectively. All rabbits were fed daily for 25 days. The
performance parameters and carcass criteria, including daily body weight gain,
final body weight, and the percentage of dressing, were increased in rabbits fed
35 % KS when compared to the control group. Kidney and liver weight ratios
increased significantly in group II but dropped in group III. Furthermore, liver
enzymes - alanine aminotransferase and aspartate transaminase and kidney function
parameters - urea, and creatinine - increased in both group II (significant
P<0.05) and in group III (significant P<0.01) when compared to the control group.
Moreover, KS leaves induced a significant increase (P<0.05) in the total white
blood cell count, the percentage of granulocytes and the platelet count; whereas,
the percentage of lymphocytes, red blood cell count, hemoglobin content, mean
corpuscular hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin
concentration were not statistically significantly changed. This study
demonstrates that the performance parameters and carcass traits are improved by
the replacement of rabbit's diet with KS leaves. However, KS leaves may adversely
affect liver and kidney function in a dose-dependent manner. Therefore, further
studies are required to elucidate the maximum tolerable and toxic, as well as
lethal doses, and to isolate the pharmacologically active components from KS
leaves.
PMID- 26417278
TI - In silico protein modeling: possibilities and limitations.
PMID- 26417279
TI - The obesity paradox is not observed in chronic heart failure patients with
metabolic syndrome.
AB - INTRODUCTION: Although being overweight or obese is a risk factor for
cardiovascular disease, obese subjects often live longer than their lean peers,
and this is known as the obesity paradox. We investigated the impact of obesity
on cardiac prognosis in chronic heart failure (CHF) patients, with or without
metabolic syndrome. DESIGN AND METHODS: We divided 374 consecutive CHF patients
into two groups according to their mean body mass index (BMI) and prospectively
followed them for 2 years. RESULTS: There were 126 cardiac events, including 32
cardiac deaths and 94 re-hospitalizations. Kaplan-Meier analysis revealed a
significantly lower cardiac event rate in the higher BMI group (log-rank test P <
0.001) in all patients and those patients without metabolic syndrome. There was
no association between BMI and cardiac prognosis in patients with metabolic
syndrome. Cox hazard analysis revealed that a higher BMI was associated with
favorable cardiac outcomes in all patients and patients without metabolic
syndrome, after adjusting for confounding factors. However, this finding did not
extend to patients with metabolic syndrome. CONCLUSIONS: The advantages of
obesity are not found in CHF patients with metabolic syndrome.
PMID- 26417275
TI - Non-alcoholic fatty liver disease, diet and gut microbiota.
AB - Non-alcoholic fatty liver disease (NAFLD) is a severe liver disease that is
increasing in prevalence with the worldwide epidemic of obesity and its related
insulin-resistance state. Evidence for the role of the gut microbiota in energy
storage and the subsequent development of obesity and some of its related
diseases is now well established. More recently, a new role of gut microbiota has
emerged in NAFLD. The gut microbiota is involved in gut permeability, low-grade
inflammation and immune balance, it modulates dietary choline metabolism,
regulates bile acid metabolism and produces endogenous ethanol. All of these
factors are molecular mechanisms by which the microbiota can induce NAFLD or its
progression toward overt non-alcoholic steatohepatitis. Modification of the gut
microbiota composition and/or its biochemical capacity by specific dietary or
pharmacological interventions may advantageously affect host metabolism. Large
scale intervention trials, investigating the potential benefit of prebiotics and
probiotics in improving cardiometabolic health in high-risk populations, are
fervently awaited.
PMID- 26417280
TI - Chemical composition and antibacterial activity of essential oils from the
Tunisian Allium nigrum L.
AB - The chemical composition of the essential oils of different Allium nigrum L.
organs and the antibacterial activity were evaluated. The study is particularly
interesting because hitherto there are no reports on the antibacterial screening
of this species with specific chemical composition. Therefore, essential oils
from different organs (flowers, stems, leaves and bulbs) obtained separately by
hydrodistillation were analyzed using gas chromatography-mass spectrometry (GC
MS). The antibacterial activity was evaluated using the disc and microdilution
assays. In total, 39 compounds, representing 90.8-96.9 % of the total oil
composition, were identified. The major component was hexadecanoic acid (synonym:
palmitic acid) in all the A. nigrum organs oils (39.1-77.2 %). We also noted the
presence of some sesquiterpenes, mainly germacrene D (12.8 %) in leaves oil) and
some aliphatic compounds such as n-octadecane (30.5 %) in bulbs oil. Isopentyl
isovalerate, 14-oxy-alpha-muurolene and germacrene D were identified for the
first time in the genus Allium L. All the essential oils exhibited antimicrobial
activity, especially against Enterococcus faecalis and Staphylococcus aureus. The
oil obtained from the leaves exhibited an interesting antibacterial activity,
with a Minimum Inhibitory Concentration (MIC) of 62.50 ug/mL against these two
latter strains. The findings showed that the studied oils have antibacterial
activity, and thus great potential for their application in food preservation and
natural health products.
PMID- 26417281
TI - Enriched environment attenuates changes in water-maze performance and BDNF level
caused by prenatal alcohol exposure.
AB - Prenatal exposure to alcohol can result in fetal alcohol syndrome (FAS),
characterized by significant changes in the physiology, structural plasticity of
hippocampal function, including long-term deficits in learning and memory.
Environmental enrichment has long been known to improve motor and cognitive
function levels, causes several neurochemical and morphological alterations in
the brain. Therefore, the effects of environmental enrichment on the
neurobehavioral and neurotrophic changes in mice exposed prenatally to alcohol
were investigated in this study. The pregnant dams were given 25 % ethanol (w/v)
or isocaloric sucrose by liquid diet from gestation day 7 to 20. After weaning on
postnatal day 28, offspring were exposed to standard cage (CC, CFAS) or enriched
living conditions (CE, EFAS) for 8 weeks. Neurobehavioral studies both on
hippocampus-dependent spatial learning and place and cue learning strategy, a
striatum-dependent test, were measured by the Morris water maze task. Moreover,
the reverse-transcriptase polymerase chain reaction (RT-PCR) technique was also
used in order to study the expression of brain-derived neurotrophic factor (BDNF)
level in both the hippocampus and striatum of mice. Neurobehavioral studies show
that animals exposed prenatally to alcohol were impaired as shown in both
hippocampal-dependent spatial/place and striatal-dependent response/cue learning
tests. Moreover, the levels of BDNF expression both in the hippocampus and
striatum of mice were also decreased. Interestingly, environmental enrichment can
ameliorate the effects of prenatal alcohol exposure both on the neurobehavioral
and neurotrophic levels. These observations indicated that enriched environment
attenuated memory impairment of prenatal alcohol exposure both in hippocampal and
striatal circuitry.
PMID- 26417282
TI - Quantification of three-dimensional structures in liver tissue: bile canalicular
and sinusoidal networks.
PMID- 26417283
TI - Exercise protects against obesity induced semen abnormalities via downregulating
stem cell factor, upregulating Ghrelin and normalizing oxidative stress.
AB - Increased oxidative stress and hormonal imbalance have been hypothesized to
underlie infertility in obese animals. However, recent evidence suggests that
Ghrelin and Stem Cell Factor (SCF) play an important role in fertility, in lean
individuals. Therefore, this study aimed at investigating whether changes in the
levels of Ghrelin and SCF in rat testes underlie semen abnormal parameters
observed in obese rats, and secondly, whether endurance exercise or Orlistat can
protect against changes in Ghrelin, SCF, and/or semen parameters in diet induced
obese rats. Obesity was modelled in male Wistar rats using High Fat Diet (HFD) 12
week protocol. Eight week-old rats (n=40) were divided into four groups, namely,
Group I: fed with a standard diet (12 % of calories as fat); Group II: fed HFD
(40 % of calories as fat); Group III: fed the HFD with a concomitant dose of
Orlistat (200 mg/kg); and Group IV: fed the HFD and underwent 30 min daily
swimming exercise. The model was validated by measuring the levels of
testosterone, FSH, LH, estradiol, leptin, triglycerides, total, HDL, and LDL
cholesterol, and final change in body weight. Levels were consistent with
published obesity models (see Results). As predicted, the HFD group had a 76.8 %
decrease in sperm count, 44.72 % decrease in sperm motility, as well as 47.09 %
increase in abnormal sperm morphology. Unlike the control group, in the HFD group
(i.e. obese rats) Ghrelin mRNA and protein were elevated, while SCF mRNA and
protein were diminished in the testes. Furthermore, in the HFD group, SOD and GPx
activities were significantly reduced, 48.5+/-5.8 % (P=0.0012) and 45.6+/-4.6 %
(P=0.0019), respectively, while TBARS levels were significantly increased
(112.7+/-8.9 %, P=0.0001). Finally, endurance exercise training and Orlistat
administration individually and differentially protected semen parameters in
obese rats. The mechanism includes, but is not limited to, normalizing the levels
of Ghrelin, SCF, SOD, GPx and TBARS. In rat testes, diet induced obesity down
regulates SCF expression, upregulates Ghrelin expression, and deteriorate
oxidative stress levels, which are collectively detrimental to semen parameters.
Exercise, and to a lesser extent Orlistat administration, protected effectively
against this detrimental effect.
PMID- 26417284
TI - EGFR tyrosine kinase targeted compounds: in vitro antitumor activity and
molecular modeling studies of new benzothiazole and pyrimido[2,1-b]benzothiazole
derivatives.
AB - In this study, we illustrate computer aided drug design of new benzothiazole and
pyrimido[2,1-b]benzothiazole derivatives as epidermal growth factor receptor
tyrosine kinase (EGFR-TK) inhibitors. Compounds 1-5 were screened at NCI, USA,
for antitumor activity against non-small cell lung cancer (NCI-H522), colon
cancer (HCT-116, HCT-15 and HT29) and breast cancer (MDA-MB-468 and MDA-MB
231/ATCC) cell lines in which EGFR is overexpressed in varying levels. Results
indicated that these compounds are more potent antitumor agents compared to
erlotinib against HT29 and MDA-MB-231/ATCC cell lines. Compound 3 showed GI50
value of 22.3 nM against NCI-H522 cell line, while erlotinib exhibited GI50 value
of 1 uM against the same cell line. In addition, these compounds were studied for
their EGFR tyrosine kinase inhibitory activity. Virtual screening utilizing
molecular modeling and QSAR techniques enabled the understanding of the
pharmacophoric requirements for antitumor activity. Docking the designed
compounds into the ATP binding site of EGFR-TK domain was done to predict the
analogous binding mode of these compounds to the EGFR-TK inhibitors.
PMID- 26417285
TI - Nesfatin-1: role as possible new anti-obesity treatment.
AB - In this article, we review on the current concepts about Nesfatin-1 as a new anti
obesity treatment and evaluate the existing issues in the context of this
knowledge and the available literature. The intent is to enable clinicians to
know Nesfatin-1 as a new anti-obesity treatment and make rational decisions based
on this perspective as possible clinical application. Future research should seek
to clarify whether Nesfatin-1 would be beneficial in the management of obesity.
PMID- 26417287
TI - Conformational changes of a chemically modified HRP: formation of a molten
globule like structure at pH 5.
AB - Horseradish peroxidase is an all alpha-helical enzyme, which widely used in
biochemistry applications mainly because of its ability to enhance the weak
signals of target molecules. This monomeric heme-containing plant peroxidase is
also used as a reagent for the organic synthesis, biotransformation,
chemiluminescent assays, immunoassays, bioremediation, and treatment of
wastewaters as well. Accordingly, enhancing stability and catalytic activity of
this protein for biotechnological uses has been one of the important issues in
the field of biological investigations in recent years. In this study, pH-induced
structural alterations of native (HRP), and modified (MHRP) forms of Horseradish
peroxidase have been investigated. Based on the results, dramatic loss of the
tertiary structure and also the enzymatic activity for both forms of enzymes
recorded at pH values lower than 6 and higher than 8. Ellipticiy measurements,
however, indicated very slight variations in the secondary structure for MHRP at
pH 5. Spectroscopic analysis also indicated that melting of the tertiary
structure of MHRP at pH 5 starts at around 45 degrees C, which is associated to
the pKa of His 42 that has a serious role in keeping of the heme prostethic group
in its native position through natural hydrogen bond network in the enzyme
structure. According to our data, a molten globule like structure of a chemically
modified form of Horseradish peroxidase at pH 5 with initial steps of
conformational transition in tertiary structure with almost no changes in the
secondary structure has been detected. Despite of some conformational changes in
the tertiary structure of MHRP at pH 5, this modified form still keeps its
catalytic activity to some extent besides enhanced thermal stability. These
findings also indicated that a molten globular state does not necessarily
preclude efficient catalytic activity.
PMID- 26417286
TI - Hydroxymethylation of DNA: an epigenetic marker.
PMID- 26417288
TI - Testing chemical carcinogenicity by using a transcriptomics HepaRG-based model?
AB - The EU FP6 project carcinoGENOMICS explored the combination of toxicogenomics and
in vitro cell culture models for identifying organotypical genotoxic- and non
genotoxic carcinogen-specific gene signatures. Here the performance of its gene
classifier, derived from exposure of metabolically competent human HepaRG cells
to prototypical non-carcinogens (10 compounds) and hepatocarcinogens (20
compounds), is reported. Analysis of the data at the gene and the pathway level
by using independent biostatistical approaches showed a distinct separation of
genotoxic from non-genotoxic hepatocarcinogens and non-carcinogens (up to 88 %
correct prediction). The most characteristic pathway responding to genotoxic
exposure was DNA damage. Interlaboratory reproducibility was assessed by blindly
testing of three compounds, from the set of 30 compounds, by three independent
laboratories. Subsequent classification of these compounds resulted in correct
prediction of the genotoxicants. As expected, results on the non-genotoxic
carcinogens and the non-carcinogens were less predictive. In conclusion, the
combination of transcriptomics with the HepaRG in vitro cell model provides a
potential weight of evidence approach for the evaluation of the genotoxic
potential of chemical substances.
PMID- 26417289
TI - Treatment with platelet lysate induces endothelial differentation of bone marrow
mesenchymal stem cells under fluid shear stress.
AB - By considering stem cell-based therapies as a new hope for the treatment of some
tragic diseases, marrow stromal cells or marrow mesenchymal stem cells (MSCs)
were considered as a suitable and safe multipotential cell source for this new
therapeutic approach. For this purpose, many investigations have been performed
on differentiation of MSCs toward specific cell lines to overcome the demand for
providing the organ specific cells for cell therapy or preparation of engineered
tissues. In the present study, differentiation of MSCs to endothelial cells (ECs)
by mechanical and chemical stimulation was evaluated. Fluid shear stress (FSS)
was used as mechanical inducer, while platelet lysate (PL) and estradiol (E) were
used as chemical induction factors. MSCs were placed under FSS with different
forces (2, 5 and 10dyn/cm(2)) for different periods (6, 12 and 24 hours). In some
groups, PL and E were added to the culture media to evaluate their effect on
expression of EC specific markers. This investigation revealed that FSS with low
tension (2.5-5 dyn/cm(2)) for a long time (24 hours) or high tension (10
dyn/cm(2)) in short time (6 hours) in the presence of PL could differentiate MSCs
toward ECs. The presence of PL was necessary for initiation of endothelial
differentiation, and in the absence of PL, there was not any expression of CD34
and Cadherin5 (Cdh5) among cells. Adding E to the culture medium did not change
the rate of endothelial differentiation under FSS. Generated endothelial
progenitors could produce von Willebrand factor (vWF) after two weeks culture and
also they formed tubular structures after culture on matrigel.
PMID- 26417290
TI - Watermelon lycopene and allied health claims.
AB - Presently, functional foods and nutraceuticals are gaining immense importance in
the prevention of various maladies through dietary regimen module. Consumption of
fruits and vegetables based diet has pursuit a range of bioactive components,
especially phytochemicals targeting life threatening ailments. In this context,
lycopene is an extensively studied antioxidant potentially present in watermelon,
tomato, pink guava etc. Watermelon is one of the unique sources having readily
available cis-isomeric lycopene. The distinctive aroma of watermelon is imparted
by medium- and short-chain fatty acids along with geranial, beta-ionone and
neral. Its consumption has been escalated owing to rich nutritional profile and
allied health benefits. It is effective in reducing the extent of cancer
insurgence, cardiovascular disorders, diabetes and macular diseases. The
structural characteristics, physiochemical properties and therapeutic effects of
lycopene are the limelight of the manuscript. However, further research
investigations are still needed to address the health enhancing potential of
watermelon lycopene.
PMID- 26417291
TI - Sodium valproate enhances urethane tumorigenicity in lungs of male but not female
mice.
AB - In the study, the possible effect of sodium valproate (NaVP) on urethane-induced
lung tumors in mice has been evaluated. BALB/c mice (n = 120; 4-6 weeks old, both
sexes) were used in the following groups: 1) urethane-treated, 2) urethane-NaVP
treated, 3) only NaVP-treated, 4) control. In the same groups, castrated male
mice (n = 48) were investigated. Urethane was given by intraperitoneal injections
10 mg/mouse, twice a week, the total dose 50 mg/mouse. In NaVP-treated mice, the
0.4 % NaVP aqueous solution was offered to mice ad libitum. The duration of the
experiment was 6 months. The number of tumors per mouse in urethane-NaVP-treated
males was significantly higher than in those treated with urethane only (13.82 +/
1.12 vs 6.77 +/- 0.43, p < 0.0001). No significant difference in the number of
tumors per mouse was revealed while comparing the female urethane- and urethane
NaVP-treated groups (6.50 +/- 0.79 vs 8.15 +/- 0.55, p = 0.105). No difference in
the number of tumors per mouse was found in urethane-NaVP-treated castrated males
as compared with urethane-treated castrated males. However, in the urethane-NaVP
treated castrated males the number of tumors per mouse was significantly lower
than in analogous non-castrated males (7.8 +/- 1.67 vs 13.82 +/- 1.12, p < 0.01).
NaVP combined with urethane potentiates urethane tumorigenicity in BALB/c non
castrated but not in female and castrated male mice. These data indicate an
important role of testosterone in the urethane-NaVP induced lung tumorigenesis.
PMID- 26417292
TI - Biochemical composition and bioactivity screening of various extracts from
Dunaliella salina, a green microalga.
AB - The current study examines the antimicrobial and antioxidant properties of
different extracts of the microalga Dunaliella salina Teodoresco
(Dunaliellaceae), their fatty acid composition and the antimicrobial activity of
the oil. Antimicrobial and antioxidant activities were evaluated by obtaining
extracts of D. salina in n-hexane, dichloromethane, ethanol, and methanol. To
evaluate the antimicrobial activity, the extracts, and fatty acids from D. salina
were assessed by the disc diffusion and microdilution techniques against
pathogenic microorganisms including fish and clinical/food-borne. The MBC or MFC
values of the extracts and fatty acids ranged from 0.63 to 10.00 mg/ml. The
antioxidant activity was studied by phosphomolybdenum and DPPH assays and beta
carotene/linoleic acid tests. In addition, the total phenolic and flavonoid
contents were evaluated and the fatty acid composition was determined using gas
chromatography. Palmitic, alpha-linolenic, and oleic acids were discovered to be
the major components of the fatty acids. These findings have demonstrated that
the extracts and oil from D. salina could be used as natural antimicrobials and
antioxidants in the food/feed and pharmaceutical industry and as a biodiesel
because of its high unsaturated fatty acid content.
PMID- 26417294
TI - Cancer incidence in North West Algeria (Mascara) 2000-2010: results from a
population-based cancer registry.
AB - Cancer is a leading cause of death worldwide accounting for 7.4 million deaths.
Cancer has become a major public health concern in Algeria. The aim of the
present study was to estimate cancer incidence in Mascara Province based on the
population-based cancer registry. We analyzed data from the cancer registry of
Mascara covering all cancer cases diagnosed by all methods and included in the
registry from 1(st) January 2000 to 31(st) December 2010. The results are
presented as incidence rates of cases by site, sex, age, and crude rate. Age
standardized rates per 100,000 person-years (ASRs) were calculated, using the
direct method of standardization to the world population. A total of 1875 cases
of invasive cancer were recorded. The mean age of diagnosis for all cancers was
52.66 +/- 0.5 in men and 59.18 +/- 0.6 in women. The ASR for all cancers in
females was 27.8 per 100,000, and that for males was 23.6 per 100,000. The most
important finding of the present study was the high incidence of liver cancer
among males and females in Mascara. Among females, breast cancer was the most
frequently reported followed by Cervix uteri, liver and colon. The most frequent
cancer types in males were lung, colon, esophagus and stomach and liver. Cancer
incidence in Mascara province was lower than that reported in other national and
regional registries. Findings of the present study revealed high incidence of
liver cancer in the province, the highest in Algeria, suggesting high prevalence
of risk factors.
PMID- 26417295
TI - Distributions of susceptibility loci of Parkinson's disease and multiple
sclerosis on human chromosomes.
PMID- 26417293
TI - Mutant p53 protein expression and antioxidant status deficiency in breast cancer.
AB - It is well recognized that cancers develop and grow as a result of disordered
function of tumor suppressor genes and oncogenes, which may be exploited for
screening purposes. Extensive evidence indicated tumor suppressor protein p53 as
candidate marker for mutation identification. We have investigated mutant p53
protein expression in human breast tumors in relation to antioxidant status
deficiency. The study included 100 breast cancer patients. p53 protein expression
was evaluated by Western blot assay and immunostaining using a CM-1, DO-7 and
Pab240 antibodies. Antioxidant parameters and lipid peroxidation were estimated
by biochemical analyses. Western blotting with epitopespecific monoclonal
antibody Pab240 strongly suggests that nuclear extracts from breast cancer cells
express mutant forms of p53. It is of interest that the mutant forms of p53
overexpression in conjunction with the appearance of nuclear bodies are observed
in highly aggressive carcinomas. Expression of isoform Deltap53 (45 kDa) and
isoform of ~ 29 kDa were more common in cases with LN metastasis. These studies
point out the molecular consequences of oxidative stress (lipid peroxides, LP,
p<0.001) and antioxidant status deficiency (copper, zinc superoxid dismutase,
SOD, p<0.001; catalase, CAT, p<0.01; glutathione reductase, GR, p<0.001;
glutathione, GSH, p<0.05) and indicate the importance of p53 mutation as the
commonest genetic alteration detected in breast cancer cells. The expression of
mutant p53 is correlated to increased lipid peroxides (0.346, p<0.05 ) and
lowered antioxidant activity of CAT (- 0.437, p<0.01) in the breast cancer
patients.
PMID- 26417297
TI - Identification of circulating miRNAs profiles that distinguish malignant pleural
mesothelioma from lung adenocarcinoma.
AB - Accurate diagnosis of malignant pleura mesothelioma (MPM) is challenging.
Differential diagnosis of MPM versus lung adenocarcinoma (AD) is particularly
difficult, yet clinically important since the two neoplasias call for different
treatment approaches. Circulating miRNA-profiling to identify miRNAs that can be
used to distinguish MPM from AD has not been reported. We conducted a wide
screening study of miRNA profiles in serum pools of MPM patients (N = 11), AD
patients (N = 36), and healthy subjects (N = 45) to identify non-invasive
biomarkers for differential diagnosis of MPM and AD, using deep sequencing.
Sequencing detected up to 300 known miRNAs and up to 25 novel miRNAs species in
the serum samples. Among known miRNAs, 7 were upregulated in MPM and 12 were
upregulated in AD compared to healthy controls. Of these, eight were distinctive
for AD and three were unique for MPM. Direct comparison of the miRNA profiles for
MPM and AD revealed differences in miRNA levels that could be useful for
differential diagnosis. No differentially expressed novel miRNAs were found.
Further bioinformatics analysis indicated that three upregulated miRNAs in MPM
are associated with the p38 pathway. There are unique alterations in serum miRNAs
in MPM and AD compared to healthy controls, as well as differences between MPM
and AD profiles. Differing miRNA levels between MPM and AD may be useful for
differential diagnosis. A potential association to p38 pathway of three
upregulated miRNAs in MPM was revealed.
PMID- 26417298
TI - Induction of spinal long-term synaptic potentiation is sensitive to inhibition of
neuronal NOS in L5 spinal nerve-transected rats.
AB - The role of neuronal nitric oxide synthase (nNOS) in the central mechanism of
neuropathic pain and long-term potentiation (LTP) of peripheral afferents remains
obscure. The current study investigated the effect of intrathecal application of
7-nitroindazole (7-NI), a selective nNOS inhibitor (8.15 ug/5ul), on mechanical
allodynia on day 14 after L5 spinal nerve transection. Furthermore, using in vivo
single unit extracellular recording, we examined the effect of 7-NI on the
induction of LTP of Adelta- and C-fiber-evoked responses. We have demonstrated
that 7-NI attenuates nerve-injury-evoked mechanical allodynia. Additionally, our
electrophysiological study has shown that the spinal administration of 7-NI
significantly inhibits the induction of the LTP of Adelta- and C-fiber-evoked
responses on day 14 after neuropathy. These data suggest that activation of nNOS
may be crucial for the induction of the spinal LTP of Adelta- and C-fiber-evoked
responses following peripheral nerve damage.
PMID- 26417296
TI - Biology of PXR: role in drug-hormone interactions.
AB - Hormonal homeostasis is essential for a variety of physiological and pathological
processes. Elimination and detoxification of xenobiotics, such as drugs
introduced into the human body, could disrupt the balance of hormones due to the
induction of drug metabolizing enzymes (DMEs) and transporters. Pregnane X
receptor (PXR, NR1I2) functions as a master xenobiotic receptor involved in drug
metabolism and drug-drug interactions by its coordinated transcriptional
regulation of phase I and phase II DMEs and transporters. Recently, increasing
evidences indicate that PXR can also mediate the endocrine disruptor function and
thus impact the integrity of the endocrine system. This review focuses primarily
on the recent advances in our understanding of the function of PXR in
glucocorticoid, mineralocorticoid, androgen and estrogen homeostasis. The
elucidation of PXR-mediated drug-hormone interactions might have important
therapeutic implications in dealing with hormone-dependent diseases and safety
assessment of drugs.
PMID- 26417300
TI - Chemical composition and antimicrobial activity of the essential oil from leaves
of Algerian Melissa officinalis L.
AB - The essential oil obtained from leaves of Melissa officinalis L. (Family of
Lamiaceae) growing in Algeria, was investigated for its chemical composition and
in vitro antimicrobial activity. The chemical composition was determined by
hydrodistillation and analyzed by GC/MS and GC-FID. Sixty-three compounds were
identified in the essential oil, representing 94.10 % of the total oil and the
yields were 0.34 %. The major component was geranial (44.20 %). Other predominant
components were neral (30.20 %) and citronellal (6.30 %). The in vitro
antimicrobial activity was determined by paper disk agar diffusion testing and
minimum inhibitory concentration (MIC) using 7 bacteria (3 Gram-positive and 4
Gram-negative), 2 yeasts and 3 fungi. The results showed that the essential oil
presented high antimicrobial activity against all microorganisms targeted mainly
against five human pathogenic bacteria, one yeast Candida albicans and two
phytopathogenic fungi tested. The minimum inhibitory concentrations (MIC) ranged
from 1.00 to 5.00 uL/mL.
PMID- 26417299
TI - Serum protein electrophoresis under effective control of HIV-1 disease
progression.
AB - In this report, we compared the serum protein electrophoresis (SPE) patterns in a
subset of HIV-1-infected subjects who did not progress to AIDS without
antiretroviral treatment with those in whose control of disease progression was
achieved by highly active antiretroviral therapy (HAART). SPE and immunofixation
electrophoresis were performed on Helena Electrophoresis System according to
manufacturer's instructions. The percentage of SPE abnormalities, resembling
chronic inflammation, was significantly higher in HIV-1-infected subject without
HAART compared with those under HAART (p = 0.001). The majority of individuals
under HAART showed evidence of oligoclonal bands on the gamma-band against a
polyclonal background compared with those without HAART but beta-gamma-band
bridging was more evident. Immunofixation pattern was consistent with oligoclonal
hypergammaglobulinaemia of IgG kappa type, which was found to be more intense in
group without HAART. HIV clinical status did not show appreciable effect on the
SPE pattern in subjects without HAART. However, under effective HAART, subjects
with better CD4 T-cell count were associated with higher gamma-globulin band. In
group without HAART, acute infection was found to be associated the higher gamma
globulin fraction compared with chronic infection. The opposite was the case
under effective HAART. HIV infected subjects that did not progress to AIDS were
associated with markedly abnormal SPE pattern. Overall results reflect the host
ability compensate defective cellular immunity in HIV-1 infection with humoral
immune responses. These findings underscore the usefulness of SPE monitoring HIV
disease management and identifying individuals that may not progress to full
blown AIDS in the absence of treatment.
PMID- 26417301
TI - Anti-inflammatory activity and chemical composition of the essential oils from
Senecio flammeus.
AB - Many species from Senecio genus have been used in traditional medicine, and their
pharmacological activities have been demonstrated. This study investigated the
chemical composition and anti-inflammatory activities of essential oils from
Senecio flammeus. A total of 48 components representing 98.41 % of the total oils
were identified. The main compounds in the oils were alpha-farnesene (11.26 %),
caryophyllene (8.69 %), n-hexadecanoic acid (7.23 %), and alpha-pinene (6.36 %).
The anti-inflammatory activity of the essential oils was evaluated in rodents (10
90 mg/kg bw) in classical models of inflammation [carrageenan-induced paw edema,
12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced ear edema, and cotton pellet
induced granuloma]. The essential oils at doses of 10, 30, and 90 mg/kg bw
significantly reduced carrageenan-induced paw edema by 17.42 % (P < 0.05), 52.90
% (P < 0.05), and 66.45 % (P < 0.05) 4 h after carrageenan injection,
respectively, and significantly reduced myeloperoxidase activity (P < 0.05). The
essential oils (10, 30, and 90 mg/kg) also produced a significant dose-dependent
response to reduce TPA-induced ear edema by 20.27 % (P < 0.05), 33.06 % (P <
0.05), and 53.90 % (P < 0.05), respectively. The essential oils produced
significant dose-response anti-inflammatory activity against cotton pellet
induced granuloma that peaked at the highest dose of 90 mg/kg (49.08 % wet weight
and 47.29 % dry weight). Results demonstrate that the essential oils of S.
flammeus were effective in the treatment of both acute and chronic inflammatory
conditions, thereby supporting the traditional use of this herb.
PMID- 26417302
TI - 6-7-Dimethoxy-4-methylcoumarin suppresses pro-inflammatory mediator expression
through inactivation of the NF-kappaB and MAPK pathways in LPS-induced RAW 264.7
cells.
AB - In this study, we investigated the ability of 6,7-dimethoxy-4-methylcoumarin
(DMC) to inhibit lipopolysaccharide (LPS)-induced expression of pro-inflammatory
mediators in mouse macrophage (RAW 264.7) cells, and the molecular mechanism
through which this inhibition occurred. Our results indicated that DMC
downregulated LPS-induced nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2
(COX-2) expression, thereby reducing the production of NO and prostaglandin E2
(PGE2) in LPS-activated RAW 264.7 cells. Furthermore, DMC suppressed LPS-induced
production of pro-inflammatory cytokines such as interleukin (IL)-1beta, IL-6,
and tumor necrosis factor (TNF)-alpha. To elucidate the mechanism underlying the
anti-inflammatory activity of DMC, we assessed its effects on the mitogen
activated protein kinase (MAPK) pathway and the activity and expression of
nuclear transcription factor kappa-B (NF-kappaB). The experiments demonstrated
that DMC inhibited LPS-induced phosphorylation of extracellular signal-regulated
kinases (ERKs), c-Jun N-terminal kinase (JNK), and p38. In addition, it
attenuated LPS-induced NF-kappaB activation via the inhibition of IkappaB-alpha
phosphorylation. Taken together, these data suggest that DMC exerts its anti
inflammatory effects in RAW 264.7 cells through the inhibition of LPS-stimulated
NF-kappaB and MAPK signaling, thereby downregulating the expression of pro
inflammatory mediators.
PMID- 26417303
TI - An overview of platelet indices for evaluating platelet function in children with
scorpion envenomation.
AB - The aim of this study was to assess the correlation between platelet indices and
scorpion envenomations (SE). Medical records of 76 children who were hospitalised
for scorpion stings in the paediatric intensive care unit (PICU) between February
2013 and November 2013, and 55 healthy children who were similar to the patient
group in terms of age and sex, were analysed retrospectively. The leucocyte
(WBC), thrombocyte (PLT), plateletcrit (PCT), platelet distribution width (PDW)
and mean platelet volume (MPV) values of the 76 children with SE were recorded.
These values were compared with the healthy control group. Significantly higher
WBC and PDW values were noted in patients with SE in comparison to the controls.
Patients with SE had significantly lower mean MPV values compared to the healthy
controls (9.03 +/- 1.26 compared to 10.43 +/- 1.44 fL, respectively; p < 0.001).
Although the mean platelet count was slightly elevated in the SE group, no
statistically significant difference existed between the two groups (p = 0.097).
Furthermore, the mean PCT values in the SE group compared to the control group
were slightly decreased, but this decrease was not statistically significant (p =
0.141). A significant inverse correlation existed between the MPV values and the
WBC (r = -0.450, p < 0.01) and PLT counts (r = -0.420, p < 0.01). The PLT values
were significantly correlated with the PCT values (r = 0.687, p < 0.01). This
study demonstrated that SE may lead to several alterations in platelet indices.
Significantly lower values of MPV and higher values of PDW were detected in SE
patients. However, the increase in the platelet counts and the decrease in the
PCT values were not significant.
PMID- 26417304
TI - Alleviation of hyperglycemia and hyperlipidemia by Phyllanthus virgatus forst
extract and its partially purified fraction in streptozotocin induced diabetic
rats.
AB - Since, we previously demonstrated that sequentially extracted methanolic fraction
showed marked antioxidant and antidiabetic property in vitro, the present study
was design to evaluate the beneficial effects of Phyllanthus virgatus methanolic
extract and its partially purified fraction on hyperglycemia and hyperlipidemia
in streptozotocin (STZ) induced diabetic rats. The plant extract was subjected to
repeated thin layer chromatographic fractionation followed by GC-MS analysis of
active fraction. TLC data illustrated the presence of six prominent bands and the
prelimnary screening of these bands against alpha-amylase inhibitory activity
showed that the band with Rf value 0.514 has marked inhibitory property (IC50, 48
ug/ml). The diabetic rats were treated for four weeks with methanolic extract of
P. virgatus (50 and 10 mg/rat/day), partially isolated active fraction (0.5 and
0.1 mg/rat/day) and glibenclamide (0.1 mg/rat/day). The level of fasting blood
glucose (FBG), hemoglobin, glycated hemoglobin (HbA1c) and insulin were
significantly alleviated in plant extract and partially purified fraction treated
group after 28 days of administration. Moreover, total cholesterol (TC),
triglycerides (TG), low density lipoprotein-cholesterol (LDL-C), very low density
lipoprotein-cholesterol (VLDL-C) and high density lipoprotein cholesterol (HDL-C)
were also markedly ameliorated in the entire treatment group, with a maximum
restoration observed in group treated with partially purified fraction (0.5
mg/rat/day). The results demonstrate a strong antidiabetic and hypolipidemic
impact of plant extract and its partially purified fraction coupled with their
potent antioxidative property, which can provide additional benefits in the
inhibition of oxidative stress and hence in the prevention and treatment of
diabetes as well as diabetes linked hyperlipidemia.
PMID- 26417305
TI - Managing post stroke hyperglycaemia: moderate glycaemic control is better? An
update.
AB - Post stroke hyperglycaemia (PSH) is prevalent in acute ischaemic stroke (AIS)
patients and it has been associated with a dismal outcome of death and
disability. Insulin has been proven to attenuate glucose effectively in stroke
patients, thus many trials over the years had studied the efficacy of intensive
treatment aiming at normalization of blood sugar level in order to improve the
bleak outcomes of PSH. However, tight glycaemic control failed to be translated
into clinical benefits and the outcomes are no different from the conventional
approach, despite the costly healthcare expenditure invested. On the contrary, it
brings more significant harm than the intended benefit, as 1 in every 9 treated
patients had symptomatic hypoglycaemia. Thus, the benefits of tight glucose
control, if any, are overshadowed by this potential risk of hypoglycaemia causing
permanent neurological injury. Therefore, international practice guidelines
recommend for less aggressive treatment to maintain blood glucose level within an
appropriate range in AIS patients. However, there are limited details for stroke
specific glycaemic management and this made management of PSH particularly
difficult. This review is to discuss and provide suggestions concerning glycaemic
control in acute ischaemic stroke; the direction of its future prospective
clinical trials and the treatment strategy required based on recent literature.
PMID- 26417306
TI - Atrial natriuretic peptide gene - a potential biomarker for long QT syndrome.
AB - This study highlights the possible implication of NPPA (natriuretic peptide
precursor A) gene in the etiology of Long QT syndrome (LQTS) by population-based
as well as familial study. Three SNPs of NPPA - C-664G, C1363A and T1766C were
examined by molecular analyses in LQTS, controls and first degree relatives
(FDRs). This study revealed a possible association of 1364 C>A SNP 'C' allele
with LQTS (p = 0.0013). All three SNPs were in tight linkage disequilibrium. The
familial study highlights the association of NPPA SNP with cLQTS and implicating
it as a potential biomarker in South Indian population.
PMID- 26417308
TI - Highlights in tumor metabolome research: Choline metabolism influences integrin
expression and supports cell attachment.
PMID- 26417307
TI - Targeting protein kinase A in cancer therapy: an update.
AB - Protein Kinase A (PKA) is a well known member of the serine-threonin protein
kinase superfamily. PKA, also known as cAMP-dependent protein kinase, is a multi
unit protein kinase that mediates signal transduction of G-protein coupled
receptors through its activation upon cAMP binding. The widespread expression of
PKA subunit genes, and the myriad of mechanisms by which cAMP is regulated within
a cell suggest that PKA signaling is one of extreme importance to cellular
function. It is involved in the control of a wide variety of cellular processes
from metabolism to ion channel activation, cell growth and differentiation, gene
expression and apoptosis. Importantly, since it has been implicated in the
initiation and progression of many tumors, PKA has been proposed as a novel
biomarker for cancer detection, and as a potential molecular target for cancer
therapy. Here, we highlight some features of cAMP/PKA signaling that are relevant
to cancer biology and present an update on targeting PKA in cancer therapy.
PMID- 26417309
TI - Isolation and structure elucidaton of polyphenols from Loranthus micranthus Linn.
parasitic on Hevea brasiliensis with antiinflammatory property.
AB - The present study was carried out to evaluate the anti-inflammatory activities of
polyphenols isolated from the leaves of mistletoe (Loranthus micranthus Linn.)
parasitic on Hevea brasiliensis. The anti-inflammatory properties of the isolated
compounds were evaluated on the basis of their ability to inhibit the production
of nitric oxide (NO) and tumuor necrosis factor-alpha (TNF-alpha) in
lipopolysaccharide (LPS) activated RAW 264.7 mouse macrophages. Semi-preparative
HPLC separation of the ethyl acetate (EtOAc) and butanol (n-BuOH) fractions of
the leaves of mistletoe (Loranthus micranthus Linn) parasitic on Hevea
brasiliensis led to the isolation of four polyphenols: 3-O-(3,4,5
trimethoxybenzoyl)-(-)-epicatechin (TMECG) (1); (-)-epicatechin-3-O-(3"-O-methyl)
gallate (ECG3"Me) (2); rutin (3) and peltatoside (4). Compounds 1-4 were isolated
for the first time from this plant while 1 was isolated for the first time in
nature. These compounds (1-4) were readily identified by comparison of their
spectroscopic data with those reported in the literature. The polyphenols proved
to have anti-inflammatory activity as evidenced by the suppression of inducible
nitric oxide (iNO) and cytokine (TNF-alpha) levels in the culture supernatant of
lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. However, the
study showed that the quercetin diglycosides showed stronger inhibition of
proinflammatory mediators than the epicatechin derivates. These data provide
evidence that polyphenolic compounds isolated from the mistletoe parasitic on
Hevea brasiliensis may contribute to its anti-inflammatory properties by
inhibiting the expression of inducible nitric oxide and proinflammatory cytokines
such as tumour necrosis factor-alpha.
PMID- 26417311
TI - Inhibitors of pancreatic lipase: state of the art and clinical perspectives.
AB - Obesity is a disorder of lipid metabolism and continues to be a global problem,
ranking fifth for deaths worldwide. It also leads to diabetes, cardiovascular
disorders, musculoskeletal disorders and some types of cancer. Obesity is
regarded as the output of a long-term imbalance between energy intake and energy
expenditure. Digestion and absorption of dietary lipids by pancreatic lipase, a
major source of excess calorie intake, can be targeted for development of anti
obesity agents. Being the major factor of concern, food materials and edible
plants are most widely studied for the anti-obesity activity, so that they can be
incorporated in the routine diet. In this review, an attempt was made to present
a current scenario of the bioactive compounds from plant and microbial origin
that have been investigated for their pancreatic lipase inhibition. Compounds
belonging to various classes of natural products such as alkaloids, carotenoids,
glycosides, polyphenols, polysaccharides, saponins and terpenoids are well
studied while lipophilic compounds from microbial sources are the most active
against the pancreatic lipase. Few studies on the synthetic analogues,
structurally similar to the triglycerides have been described in the review.
Despite of tremendous research on the finding of potential pancreatic lipase
inhibitor, very few compounds have entered the clinical studies and no new
molecule after orlistat has been marketed. Along with HTS based screening,
detailed structure-activity relationship studies on semi-synthetic and synthetic
derivatives might also provide a direction for the development of potential
lead(s) or pharmacophore for pancreatic lipase inhibition in order to treat
and/or prevent obesity and related disorders.
PMID- 26417310
TI - Cytochrome P450 enzyme mediated herbal drug interactions (Part 2).
AB - To date, a number of significant herbal drug interactions have their origins in
the alteration of cytochrome P450 (CYP) activity by various phytochemicals. Among
the most noteworthy are those involving St. John's wort and drugs metabolized by
human CYP3A4 enzyme. This review article is the continued work from our previous
article (Part 1) published in this journal (Wanwimolruk and Prachayasittikul,
2014[ref:133]). This article extends the scope of the review to six more herbs
and updates information on herbal drug interactions. These include black cohosh,
ginseng, grape seed extract, green tea, kava, saw palmetto and some important
Chinese medicines are also presented. Even though there have been many studies to
determine the effects of herbs and herbal medicines on the activity of CYP, most
of them were in vitro and in animal studies. Therefore, the studies are limited
in predicting the clinical relevance of herbal drug interactions. It appeared
that the majority of the herbal medicines have no clear effects on most of the
CYPs examined. For example, the existing clinical trial data imply that black
cohosh, ginseng and saw palmetto are unlikely to affect the pharmacokinetics of
conventional drugs metabolized by human CYPs. For grape seed extract and green
tea, adverse herbal drug interactions are unlikely when they are concomitantly
taken with prescription drugs that are CYP substrates. Although there were few
clinical studies on potential CYP-mediated interactions produced by kava, present
data suggest that kava supplements have the ability to inhibit CYP1A2 and CYP2E1
significantly. Therefore, caution should be taken when patients take kava with
CYP1A2 or CYP2E1 substrate drugs as it may enhance their therapeutic and adverse
effects. Despite the long use of traditional Chinese herbal medicines, little is
known about the potential drug interactions with these herbs. Many popularly used
Chinese medicines have been shown in vitro to significantly change the activity
of human CYP. However, with little confirming evidence from clinical studies,
precaution should be exercised when patients are taking Chinese herbal medicines
concomitantly with drugs that are CYP substrates. Currently there is sufficient
evidence to indicate that herbal drug interactions can occur and may lead to
serious clinical consequence. Further clinical trial research should be conducted
to verify these herbal drug interactions. Education on herbal drug interactions
and communication with patients on their use of herbal products is also
important.
PMID- 26417312
TI - Classification of oxidative stress based on its intensity.
AB - In living organisms production of reactive oxygen species (ROS) is
counterbalanced by their elimination and/or prevention of formation which in
concert can typically maintain a steady-state (stationary) ROS level. However,
this balance may be disturbed and lead to elevated ROS levels called oxidative
stress. To our best knowledge, there is no broadly acceptable system of
classification of oxidative stress based on its intensity due to which proposed
here system may be helpful for interpretation of experimental data. Oxidative
stress field is the hot topic in biology and, to date, many details related to
ROS-induced damage to cellular components, ROS-based signaling, cellular
responses and adaptation have been disclosed. However, it is common situation
when researchers experience substantial difficulties in the correct
interpretation of oxidative stress development especially when there is a need to
characterize its intensity. Careful selection of specific biomarkers (ROS
modified targets) and some system may be helpful here. A classification of
oxidative stress based on its intensity is proposed here. According to this
classification there are four zones of function in the relationship between
"Dose/concentration of inducer" and the measured "Endpoint": I - basal oxidative
stress (BOS); II - low intensity oxidative stress (LOS); III - intermediate
intensity oxidative stress (IOS); IV - high intensity oxidative stress (HOS). The
proposed classification will be helpful to describe experimental data where
oxidative stress is induced and systematize it based on its intensity, but
further studies will be in need to clear discriminate between stress of different
intensity.
PMID- 26417313
TI - Platismatia glaucia and Pseudevernia furfuracea lichens as sources of
antioxidant, antimicrobial and antibiofilm agents.
AB - The antioxidative, antimicrobial and antibiofilm potentials of acetone, ethyl
acetate and methanol extracts of lichen species Platismatia glauca and
Pseudevernia furfuracea were evaluated. The phytochemical analysis by GC, GC/MS
and NMR revealed caperatic acid, atraric acid, atranorin and chloroatranorin as
the predominant compounds in Platismatia glauca. Atraric acid, olivetoric acid,
atranorin and chloroatranorin were the major constituents in Pseudevernia
furfuracea. The strong antioxidant capacities of the Platismatia glauca and
Pseudevernia furfuracea extracts were assessed by their total phenolic and
flavonoid contents and DPPH scavenging activities. The methanol extracts of both
species exhibited the strongest antioxidant activities with the highest IC50
value for Pseudevernia furfuracea (95.33 ug/mL). The lichen extracts demonstrated
important antibacterial activities against 11 bacterial strains with detectable
MIC values from 0.08 mg/mL to 2.5 mg/mL for Platismatia glauca and from 0.005
mg/mL to 2.5 mg/mL for Pseudevernia furfuracea. While the antibacterial
activities of Pseudevernia furfuracea were solvent-independent, the acetone and
ethyl acetate extracts of Platismatia glauca showed higher antibacterial
activities compared to its methanol extract. The methanol extracts of both
species demonstrated significant antifungal activities against 9 fungal strains
with detectable MIC values from 0.04 mg/mL to 2.5 mg/mL. The best antifungal
activities were determined against Candida species in Pseudevernia furfuracea
extracts with remarkable MIC values which were lower than the MIC values of the
positive contol fluconazole. The acetone and ethyl acetate extracts of
Platismatia glauca showed better antibiofilm activities on Staphylococcus aureus
and Proteus mirabilis with BIC value at 0.63 mg/mL then its methanol extract. On
the other hand, the methanol extract of Pseudevernia furfuracea was more potent
with BIC value at 1.25 mg/mL on Staphylococcus aureus and 0.63 mg/mL on Proteus
mirabilis compared to other types of extracts. Our study indicates a possible use
of lichens Platismatia glauca and Pseudevernia furfuracea as natural antioxidants
and preservatives in food, pharmaceutical and cosmetic industry.
PMID- 26417314
TI - Epigenetics in diagnosis, prognostic assessment and treatment of cancer: an
update.
AB - Cancer cells contain multiple genetic and epigenetic changes. The relative
specificity of many epigenetic changes for neoplastic cells has allowed the
identification of diagnostic, prognostic and predictive biomarkers for a number
of solid tumors and hematological malignancies. Moreover, epigenetically-acting
drugs are already in routine use for cancer and numerous additional agents are in
clinical trials. Here, we review recent progress in the development and
application of epigenetic strategies for the diagnosis, risk stratification and
treatment of cancer.
PMID- 26417316
TI - Antimicrobial and antioxidative activities in the bark extracts of Sonneratia
caseolaris, a mangrove plant.
AB - The present study deals with the phytochemical contents, antimicrobial and
antioxidative activities of bark tissue of Sonneratia caseolaris, a mangrove
plant from Sundarban estuary, India. Phytochemical analyses revealed the presence
of high amounts of phenolics, flavonoids, tannins, alkaloids and saponins.
Antimicrobial efficacies of various extracts of S. caseolaris were assessed by
disc diffusion method against two Gram-positive (Bacillus subtilis and Bacillus
coagulans), two Gram-negative (Escherichia coli and Proteus vulgaris) bacteria
and one fungus (Saccharomyces cerevisiae). The methanolic extract among others
showed significant minimum inhibitory concentration (MIC) values. The antioxidant
activity as indicated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity
of the bark tissue extract from the species was found to be quite appreciable.
The extracts were found to retain their antimicrobial activities despite pH and
thermal treatments, thus indicating the stability of their activity even at
extreme conditions. The antioxidant activity was also found to be considerably
stable after thermal treatments. The components of the tissue extracts were
subjected to separation using thin layer chromatography (TLC). The constituents
with antimicrobial and antioxidative properties were identified using TLC
bioautography by agar-overlay and DPPH spraying methods respectively. A number of
bioactive constituents with antimicrobial and radical scavenging properties were
observed on the developed bioautography plate. The fractions with antimicrobial
properties were isolated from the reference TLC plates and subjected to gas
chromatography-mass spectrometry (GC-MS) analysis for partial characterization
and identification of the metabolites that might be responsible for the
activities. The study suggests Sonneratia caseolaris bark as a potential source
of bioactive compounds with stable antimicrobial and antioxidative properties and
can be used as natural antimicrobial/antioxidative agents in clinical,
pharmaceutical and food processing industries.
PMID- 26417317
TI - Suppressive effects of Mimosa pudica (L.) constituents on the production of LPS
induced pro-inflammatory mediators.
AB - The present study deals with the isolation of fourteen compounds from the active
ethyl acetate (MPE) extract of M. pudica (L.) whole plant and their subsequent
evaluation for the nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha) and
interleukin 1 beta (IL-1beta) inhibitory activities in lipopolysaccharide (LPS)
stimulated RAW 264.7 and J774A.1 cells. Among the tested compounds, L-mimosine
(12; IC50 = 19.23 to 21.15 uM), crocetin (4; IC50 = 23.45 to 25.57 uM), crocin
(14; IC50 = 27.16 to 31.53 uM) and jasmonic acid (11; IC50 = 21.32 to 29.42 uM)
were identified as potent NO inhibitor when tested on the macrophages. Similarly,
towards TNF-alpha and IL-1beta inhibition, including these four compounds, and
ethyl gallate (3), gallic acid (10) and caffeic acid (7) were found to be more
active with half maximal concentration, 17.32 to 62.32 uM whereas the other
compounds depicted moderate and mild effects (IC50 = 59.32 to 95.01 uM). Also, at
a dose of 40 mg/Kg, L-mimosine (12), jasmonic acid (11), crocin (14) and its de
esterified form, crocetin (4) were found to significantly (p < 0.05 and 0.001)
reduce 60.7 %, 48.9 %, 48.4 % and 43.6 % respectively of TNF-de-esterified
production in female Sprague Dawley rats. However, in case of IL-1beta, with the
same dose (40 mg/Kg), jasmonic acid (11) exhibited significant reduction with
54.2 % followed by crocin (14) (50.2 %) and crocetin (4) (39.8 %) while L
mimosine (12) was found to reduce only 16.3 %. Based on the results, it can be
estimated that these compounds imparting greatly to anti-inflammatory effects of
M. pudica in vitro as well as in vivo through reduction of LPS-induced pro
inflammatory mediators which affirm the ethno-pharmacological use of this plant
for prevention of inflammatory-related disorders.
PMID- 26417318
TI - Synthesis and antibacterial activity of a new derivative of the Meldrun acid: 2,2
dimethyl-5-(4H-1,2,4-triazol-4-ylaminomethylene)-1,3-dioxane-4,6-dione
(C9H10N4O4).
AB - The discovery of new substances with proven antimicrobial activity is the current
study goal of various researchers. Usage of synthetic products has grown
considerably in the past few years due to processing agility, and capability of
going through previous chemical modifications in order to enhance its biological
activity. Widespread careless use of antimicrobials has made the number of
resistant microorganisms rise significantly, thus demanding more efficient drugs
to fight them. One of these synthetic candidates for this purpose is the
substance 2,2-Dimethyl-5-(4H-1,2,4-triazol-4-ylaminomethylene)-1,3-dioxane-4,6
dione (C9H10N4O4), aminomethylene derivative from Meldrum's acid. This substance,
alone and in association with common antibiotics, were evaluated in vitro for
antimicrobial activity, and had their minimum inhibitory concentration (MIC)
towards Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 10536 and
Pseudomonas aeruginosa ATCC 15442, as well as multiresistant strains Escherichia
coli 27, Staphylococcus aureus 358 and Pseudomonas aeruginosa 03 determined. The
antimicrobial modulation action tests of the aminoglycosides with C9H10N4O4 were
performed according to the microdilution method, and resulted in observation of a
positive synergic effect.
PMID- 26417319
TI - Combined anti-ages and antioxidant activities of different solvent extracts of
Solanum elaeagnifolium Cav (Solanacea) fruits during ripening and related to
their phytochemical compositions.
AB - Oxidative stress and advanced glycation end products (AGEs) are known as key
factors for the development of diabetic complications such as retinopathy,
cataract as well as atherosclerosis and neurodegenerative diseases, including
Alzheimer's diseases. In this context, natural products have been previously
identified as promising sources for antioxidant and anti-glycation compounds. The
current study focuses on the evaluation of antioxidant and glycation inhibitory
activities of different solvent extracts of Solanum elaeagnifolium Cav
(Solanaceae) fruits at different ripening stages. The results showed that
antioxidant and anti-AGEs activities were significantly influenced by solvents
polarities and ripening stages of S. elaeagnifolium Cav. With one exception,
methanolic extract of overripe S. elaeagnifolium Cav fruit showed important
protective effects against cellular oxidative stress. The aqueous extract showed
the highest ABTS(+) scavenging ability. Principal component analysis showed that
total phenolic and flavonoid contents correlated well with observed antioxidants
and anti-glycation activities. These results bring attention to the possible use
of S. elaeagnifolium Cav as a valuable source of bioactive compounds exhibiting
antioxidant effects and potentially alleviating diabetic complications.
PMID- 26417315
TI - Hepatitis C virus infection: establishment of chronicity and liver disease
progression.
AB - Hepatitis C virus (HCV) often causes persistent infection, and is an important
factor in the etiology of fibrosis, cirrhosis, and hepatocellular carcinoma
(HCC). There are no preventive or therapeutic vaccines available against HCV.
Treatment strategies of HCV infection are likely to improve with recently
discovered direct antiviral agents (DAAs). However, a proportion of patients
still progress to liver failure and/or HCC despite having been cured of the
infection. Thus, there is a need for early diagnosis and therapeutic modalities
for HCV related end stage liver disease prevention. HCV genome does not integrate
into its host genome, and has a predominantly cytoplasmic life cycle. Therefore,
HCV mediated liver disease progression appears to involve indirect mechanisms
from persistent infection of hepatocytes. Studying the underlying mechanisms of
HCV mediated evasion of immune responses and liver disease progression is
challenging due to the lack of a naturally susceptible small animal model. We and
other investigators have used a number of experimental systems to investigate the
mechanisms for establishment of chronic HCV infection and liver disease
progression. HCV infection modulates immune systems. Further, HCV infection of
primary human hepatocytes promotes growth, induces phenotypic changes, modulates
epithelial mesenchymal transition (EMT) related genes, and generates tumor
initiating stem-like cells (TISCs). HCV infection also modulates microRNAs
(miRNAs), and influences growth by overriding normal death progression of primary
human hepatocytes for disease pathogenesis. Understanding these ob-servations at
the molecular level should aid in developing strategies for additional effective
therapies against HCV mediated liver disease progression.
PMID- 26417320
TI - Scientific validation of cardioprotective attribute by standardized extract of
Bombyx mori against doxorubicin-induced cardiotoxicity in murine model.
AB - Doxorubicin (DOX) is an excellent antineoplastic agent used for the treatment of
hematological and solid malignancies. The aqueous extract of Bombyx mori (BMAE)
contains amino acids and some flavonoids with obvious cardioprotective effect.
The aim of this study was to investigate the possible protective effect of BMAE
against DOX-induced cardiotoxicity and its underlying mechanisms on murine model.
The metabolic profiling of BMAE was carried out by Ultra Performance Liquid
Chromatography-Mass Spectrometry (UPLC-MS) and the amino acid profiling by HPLC
method using fluorescence detector (HPLC-FLD). The biochemical parameter like
caspase-3, tumor necrosis factor-alpha (TNF-alpha), interleukin -6 (IL-6),
creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA)
were studied. Tissue damage was further evaluated by histopathological studies.
The metabolic profiling of BMAE exhibited presence of quercetin 7-O-beta-D
glucoside, kaempferol 7-O-beta-D-glucopyranoside, coumaric acid glucoside, 2
hydroxy-nonadecanoic acid and 9,12-dihydroxy stearic acid as important
constituents. The amino acid profile by HPLC-FLD showed presence of 17 amino
acids. The BMAE showed prominent free radical scavenging activity when assessed
by the H2O2 and super-oxide method. The results of present investigation showed
protection against DOX-induced oxidative stress (lipid peroxidation), by
reverting activities of apoptotic markers (caspase-3 and TNF-alpha), cardiac
markers (CK-MB and LDH activities) as well as pro-inflammatory marker IL-6
followed by oral administration of BMAE. In addition, results of histopathology
also supported well the above results. It was observed that BMAE protects DOX
induced cardiotoxicity by virtue of its antioxidants possibly by flavonoids and
amino acids.
PMID- 26417321
TI - Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin
resistant rats.
AB - Synthetic 3-hydroxyflavone analogues (JY-1, JY-2, JY-3, JY-4), were tested for
antidiabetic activity in high-fructose-diet-fed (66 %, for 6 weeks) insulin
resistant Wistar rats (FD-fed rats). The fasting blood glucose, insulin,
creatinine and AGEs were decreased to near normal upon treatment with test
compounds. Insulin resistance markers such as HOMA-IR, K-ITT, plasma
triglycerides, lipids, endogenous antioxidant defense and glycogen were restored
in FD-fed rats after treatment with 3-hydroxyflavones. It is known that insulin
resistance is partly because of oxidative stress and hence antioxidant activity
was determined. They exhibited significant in vitro DPPH and ABTS radical
scavenging activity (IC50: 10.66-66.63 uM). Test compounds inhibited ROS and NO
production in RAW 264.7 cells (IC50: 10.39-42.63 uM) and they were found as
potent as quercetin. Further, the test compounds inhibited lipid peroxidation at
low concentrations (IC50: 99.61-217.47 uM). All test compounds at concentrations
100-200 uM protected calf thymus DNA-damage by Fenton reaction. In addition, test
compounds inhibited protein glycation in different in vitro antiglycation assays.
JY-2 showed maximum potency in all the stages of glycation which was comparable
to the standard quercetin and aminoguanidine. Test compounds also enhanced the
glucose uptake by L6 myotubes at an EC50 much lower than that of quercetin. Thus
the synthetic 3-hydroxyflavones were found to have good antidiabetic activity by
pleotropic and multimodal suppression of insulin resistance and enhancement of
glucose uptake by skeletal muscles. These compounds are non-toxic at the doses
tested. Further, the combined antioxidant and antiglycation activities of these
molecules have complementary benefits in management of diabetes.
PMID- 26417323
TI - Anti-inflammatory effect of selagin-7-O-(6''-O-acetyl-)-beta-D-glycoside isolated
from Cancrinia discoidea on lipopolysaccharide-induced mouse macrophage RAW 264.7
cells.
AB - Selagin-7-O-(6''-O-acetyl-)-beta-D-glycoside, a new flavone glycoside isolated
from Cancrinia discoidea, is known to exhibit anti-inflammatory activity in vivo.
This study aimed to investigate the protection of this flavone glycoside on
inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The effects
of selagin-7-O-(6''-O-acetyl-)-beta-D-glycoside on inflammatory cytokines and
signaling pathways were analyzed by enzyme-linked immunosorbent assay, reverse
transcription-polymerase chain reaction, and western blot. Results show that
selagin-7-O-(6''-O-acetyl-)-beta-D-glycoside protected LPS-induced macrophage RAW
264.7 cells from injury. The flavone glycoside markedly inhibited the LPS-induced
production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6
and increased interleukin-10 release in a concentration-dependent manner.
Furthermore, treatment with the flavone glycoside decreased nitric oxide and
prostaglandin E2 in LPS-challenged RAW 264.7 cells. These decreases were
associated with the down-regulation of inducible nitric oxide synthase (iNOS),
cyclooxygenase (COX-2), and nuclear factor kappa B (NF-kappaB) activity. These
findings suggest that the anti-inflammatory effects of selagin-7-O-(6''-O-acetyl
)-beta-D-glycoside were associated with the adjustment of inflammatory cytokines,
and attributed to the down-regulation of NF-kappaB and consequent suppression of
the expression of iNOS and COX-2.
PMID- 26417322
TI - Endoplasmic reticulum membrane potassium channel dysfunction in high fat diet
induced stress in rat hepatocytes.
AB - In a previous study we reported the presence of a large conductance K(+) channel
in the membrane of endoplasmic reticulum (ER) from rat hepatocytes. The channel
open probability (Po) appeared voltage dependent and reached to a minimum 0.2 at
+50 mV. Channel activity in this case was found to be totally inhibited at ATP
concentration 2.5 mM, glibenclamide 100 uM and tolbutamide 400 uM. Existing
evidence indicates an impairment of endoplasmic reticulum functions in ER stress
condition. Because ER potassium channels have been involved in several ER
functions including cytoprotection, apoptosis and calcium homeostasis, a study
was carried out to consider whether the ER potassium channel function is altered
in a high fat diet model of ER stress. Male Wistar rats were made ER stress for 2
weeks with a high fat diet. Ion channel incorporation of ER stress model into the
bilayer lipid membrane allowed the characterization of K(+) channel. Our results
indicate that the channel Po was significantly increased at voltages above +30
mV. Interestingly, addition of ATP 7.5 mM, glibenclamide 400 uM and tolbutamide
2400 uM totally inhibited the channel activities, 3-fold, 4-fold and 6-fold
higher than that in the control groups, respectively. Our results thus
demonstrate a modification in the ER K(+) channel gating properties and decreased
sensitivity to drugs in membrane preparations coming from ER high fat model of ER
stress, an effect potentially linked to a change in ER K(+) channel subunits in
ER stress condition. Our results may provide new insights into the cellular
mechanisms underlying ER dysfunctions in ER stress.
PMID- 26417324
TI - Neuroprotection by diarylpropionitrile in mice with spinal cord injury.
AB - The initial impact of spinal cord injury (SCI) often results in inflammation
leading to irreversible damage with consequent loss of locomotor function.
Minimal recovery is achieved once permanent damage has occurred. Using a mouse
model of SCI we observed a transitory increase followed by a rapid decline in
gene expression and protein levels of nuclear factor erythroid 2-related factor 2
(Nrf2), a master regulator of cellular anti-oxidative genes. Immediate treatment
with diarylpropionitrile (DPN), a non-steroidal selective estrogen receptor beta
ligand, resulted in a significant increase in Nrf2 levels, and reduction of
inflammation and apoptosis compared to untreated SCI animals. Furthermore, DPN
treatment improved locomotor function within 7 days after induction of SCI. DPN
acted through activation of PI3K/ Akt pathway, known to be involved in down
regulation of apoptosis and up-regulation of cell survival in injured tissues.
These findings suggest that immediate activation of cellular anti-oxidative
stress mechanisms should provide protection against irreversible tissue damage
and its profound detrimental effect on locomotor function associated with SCI.
PMID- 26417325
TI - In vitro control of plant pathogenic Xanthomonas spp. using Poncirus trifoliata
Rafin.
AB - The secondary metabolites such as essential oil and pure compounds (limonin and
imperatorin) from Poncirus trifoliata Rafin were tested for in vitro control of
phytopathogenic bacteria of Xanthomonas spp. In vitro studies showed that the oil
had inhibitory effect on Xanthomonas campestris pv. compestris KC94-17-XCC,
Xanthomonas campestris pv. vesicatoria YK93-4-XCV, Xanthomonas oryzae pv. oryzae
KX019-XCO and Xanthomonas sp. SK12 with their inhibition zones and minimum
inhibitory concentration (MIC) values ranging from 13.1~22.1 mm and 62.5~125
MUg/ml, respectively. Limonin and imperatorin also had in vitro antibacterial
potential (MIC: 15.62~62.5 MUg/ml) against all the tested Xanthomonas spp.
Furthermore, the SEM studies demonstrated that limonin and imperatorin caused
morphological changes of Xanthomonas sp. SK12 at the minimum inhibitory
concentration (15.62 MUg/ml). These results of this study support the possible
use of essential oil and natural compounds from P. Trifoliata in agriculture and
agro-industries to control plant pathogenic microorganisms.
PMID- 26417326
TI - Renin inhibitors in diabetes and hypertension: an update.
AB - The coexistence of hypertension and diabetes increases the incidence of
cardiovascular events and long-term morbidity and mortality. Blood pressure
should be controlled with the most appropriate drugs as well as tight blood
glucose control in patients with diabetes and hypertension. RAAS (Renin
Angiotensin Aldosterone System) blockers have an important role in the treatment
of these patients, in this sense, ACEi and ARB remained the major treatment
option in hypertension guidelines. The most recent RAAS blocker to be approved by
the FDA was aliskiren in 2007, a renin inhibitor. Studies showed that aliskiren
is as effective as other antihypertensive drugs and has a safety profile similar
to placebo. The potent renin inhibitor aliskiren directly inhibits the RAAS
system at its rate limiting step and differently from other RAAS blockers; it
decreases plasma renin activity (PRA). Although the relationship of increased PRA
levels and cardiovascular risk has been shown, it is unclear if the PRA decrease
provided by aliskiren has an impact on clinical outcomes and cardiovascular
endpoints. On the other hand, large trials like ASPIRE, AVANT-GARDE, ALTITUDE,
ASTRONAUT, which investigated the combination of aliskiren with other RAAS
blockers, failed to show the expected outcomes or resulted with an increased
incidence of adverse effects, which raised more questions. As a result of the
ALTITUDE trial, combination of aliskiren with an ACEi or ARB is not recommended
in patients with hypertension and diabetes, or at least moderate renal
dysfunction. Trials designed to prove aliskiren's efficacy in new indications
like diabetes, may face similar problems related to dual RAAS blockade because in
the majority of cases, the optimal treatment is achieved with an ACEi or ARB. In
this conjuncture, the increase in adverse events seen with aliskiren might be
related to dual RAAS blockade rather than aliskiren directly. For instance, it is
unclear whether the adverse event incidence would be the same, less, or higher if
ALTITUDE was designed to investigate ACEi and ARB combination without aliskiren.
In fact, every new molecular entity and mechanism of action faces the same
barriers. For the time being, differentiating points like PRA lowering effects as
an add-on therapy to calcium channel blockers or hydrochlorothiazide, and the
populations that might have additional benefit, should be carefully investigated.
PMID- 26417327
TI - Chemical stimulation of the lateral hypothalamus potentiated the sensitization to
morphine in rats: involvement of orexin-1 receptor in the ventral tegmental area.
AB - Orexin plays a crucial role in drug-seeking behavior. The lateral hypothalamus
(LH) is a central region that produces orexin, and its projections to the ventral
tegmental area (VTA) play an important role in reward and addiction-related
behaviors. In this study, we investigated the role of LH stimulation and the
involvement of the orexin-1 receptor (Ox1r) in the VTA in relation to morphine
sensitization. In all animals, cannulae were implanted unilaterally into the LH
and VTA to inject different doses of carbachol (62.5, 125 and 250 nmol/0.5 MUl
saline) as a cholinergic agonist and SB334867 (1, 10 and 20 nmol/0.3 ul DMSO) as
a selective Ox1r antagonist for three consecutive days (sensitization period)
respectively. These drugs were injected five minutes before administration of an
ineffective dose of morphine (0.5 mg/kg; sc) during the sensitization period. In
all groups, the sensitization period occurred in a separate room from which the
conditioning occurred. After this period, all groups exceeded five days under the
conditioned place preference (CPP) paradigm without any treatment. For evaluation
of morphine sensitization, place preference was induced by ineffective dose of
morphine (0.5 mg/kg) and the CPP score was represented by the difference in time
spent in drug- and saline-paired compartments. The results revealed that
concurrent intra-LH administration of carbachol (125 nmol/0.5 ul saline) and an
ineffective dose of morphine (0.5 mg/kg) significantly induce CPP. Additionally,
the blockade of Ox1r in the VTA by SB334867 can attenuate the conditioning score
induced by concurrent administration of carbachol and an ineffective dose of
morphine. Our findings suggest that LH stimulation potentiates the effect of an
ineffective dose of morphine, and induces morphine sensitization. It seems that
the chemical stimulation of LH potentiates sensitization to morphine through the
orexinergic system in the VTA in rats.
PMID- 26417328
TI - Immune mediated liver failure.
AB - Liver failure is a clinical syndrome of various etiologies, manifesting as
jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result
in subsequent multiorgan failure. Clinically, liver failure is classified into
four categories: acute, subacute, acute-on-chronic and chronic liver failure.
Massive hepatocyte death is considered to be the core event in the development of
liver failure, which occurs when the extent of hepatocyte death is beyond the
liver regenerative capacity. Direct damage and immune-mediated liver injury are
two major factors involved in this process. Increasing evidence has suggested the
essential role of immune-mediated liver injury in the pathogenesis of liver
failure. Here, we review the evolved concepts concerning the mechanisms of immune
mediated liver injury in liver failure from human and animal studies. Both innate
and adaptive immunity, especially the interaction of various immune cells and
molecules as well as death receptor signaling system are discussed. In addition,
we highlight the concept of "immune coagulation", which has been shown to be
related to the disease progression and liver injury exacerbation in HBV related
acute-on-chronic liver failure.
PMID- 26417329
TI - Role of tight junctions in signal transduction: an update.
AB - Tight junctions (TJs), which are the most apically located of the intercellular
junctional complexes, have a barrier function and a fence function. Recent
studies show that they also participate in signal transduction mechanisms. TJs
are modulated by intracellular signaling pathways including protein kinase C,
mitogen-activated protein kinase, and NF-kappaB, to affect the epithelial barrier
function in response to diverse stimuli. TJs are also regulated by various
cytokines, growth factors, and hormones via signaling pathways. To investigate
the regulation of TJ molecules via signaling pathways in human epithelial cells
under normal and pathological conditions, we established a novel model of human
telomerase reverse transcriptase-transfected human epithelial cells. In this
review, we describe the recent progress in our understanding of the role of TJs
for signal transduction under normal conditions in upper airway epithelium,
pancreatic duct epithelial cells, hepatocytes, and endometrial epithelial cells,
and in pathological conditions including cancer and infection.
PMID- 26417331
TI - Recent studies on rosmarinic acid and its biological and pharmacological
activities.
PMID- 26417330
TI - Clinical pharmacology of atypical antipsychotics: an update.
AB - This review will concentrate on the clinical pharmacology, in particular
pharmacodynamic data, related to atypical antipsychotics, clozapine, risperidone,
paliperidone, olanzapine, que!tiapine, amisulpride, ziprasidone, aripiprazole,
asenapine, iloperidone, lurasidone and cariprazine. A summary of their acute
pharmacokinetics properties are also reported. Four new second-generation
antipsychotics are available: iloperidone, asenapine, lurasidone and in the next
future cariprazine. Similar to ziprasidone and aripiprazole, these new agents are
advisable for the lower propensity to give weight gain and metabolic
abnormalities in comparison with older second-generation antipsychotics such as
olanzapine or clozapine. Actually lurasidone seems to be best in terms of
minimizing unwanted alterations in body weight and metabolic variables.
Therapeutic drug monitoring is not strictly necessary for all of the new
antipsychotic drugs because there are no unequivocal data supporting a
relationship between plasma drug levels and clinical outcomes or side effects.
The exception can be represented by clozapine for which plasma levels of 350-420
ng/ml are reported to be associated with an increased probability of a good
clinical response. Also for olanzapine an established therapeutic range (20-50
ng/ml) is proposed to yield an optimal response and minimize side effects.
PMID- 26417332
TI - Gebel-criteria for risk assessment in nanotoxicology.
PMID- 26417333
TI - The post GWAS era: strategies to identify gene-gene and gene-environment
interactions in urinary bladder cancer.
PMID- 26417334
TI - Thermography based breast cancer detection using texture features and minimum
variance quantization.
AB - In this paper, we present a system based on feature extraction techniques and
image segmentation techniques for detecting and diagnosing abnormal patterns in
breast thermograms. The proposed system consists of three major steps: feature
extraction, classification into normal and abnormal pattern and segmentation of
abnormal pattern. Computed features based on gray-level co-occurrence matrices
are used to evaluate the effectiveness of textural information possessed by mass
regions. A total of 20 GLCM features are extracted from thermograms. The ability
of feature set in differentiating abnormal from normal tissue is investigated
using a Support Vector Machine classifier, Naive Bayes classifier and K-Nearest
Neighbor classifier. To evaluate the classification performance, five-fold cross
validation method and Receiver operating characteristic analysis was performed.
The verification results show that the proposed algorithm gives the best
classification results using K-Nearest Neighbor classifier and a accuracy of
92.5%. Image segmentation techniques can play an important role to segment and
extract suspected hot regions of interests in the breast infrared images. Three
image segmentation techniques: minimum variance quantization, dilation of image
and erosion of image are discussed. The hottest regions of thermal breast images
are extracted and compared to the original images. According to the results, the
proposed method has potential to extract almost exact shape of tumors.
PMID- 26417335
TI - Synthesis of novel antimicrobial aryl himachalene derivatives from naturally
occurring himachalenes.
AB - Five new 2,9,9-trimethyl-6,7,8,9-tetrahydro-benzocyclohepten-5-ylidene-amine
derivatives (16a-16e) were synthesized from alpha-dehydro-ar-himachalene (11)
that was originally prepared from an isomeric mixture of alpha, beta and gamma
himachalenes (10), the abundant sesquiterpenes of Cedrus deodara essential oil.
In addition, different aryl himachalenes derivatives (9, 12, 14 and 15) were also
formed from 11. The structures of the synthesized compounds were confirmed on the
basis of their NMR, IR and mass spectral data. The prepared compounds were tested
against a group of sixteen organisms including gram positive and gram negative
bacterial and fungal strains. The introduction of a series of substituted imine
groups into aryl himachalenes at 5(th) position (16a-16e) enhanced antimicrobial
activity as compared to the aromatized derivatives (9, 12, 14 and 15) against
gram-positive bacteria Bacillus subtilis, Micrococcus luteus and Staphylococcus
aureus, and mycotoxigenic fungi Aspergillus parasiticus, A. ochraceous and A.
sydowii. graphical Abstract, Figure 1(Fig. 1).
PMID- 26417336
TI - Biological activities and chemical composition of lichens from Serbia.
AB - The aim of this study is to investigate chemical composition of acetone extracts
of the lichens Parmelia arseneana and Acarospora fuscata and in vitro
antioxidant, antimicrobial, and anticancer activities of these extracts and
gyrophoric acid isolated from A. fuscata. The HPLC-UV method was used for the
identification of secondary metabolites. Stictic acid, norstictic acid,
gyrophoric acid, usnic acid, atranorin and chloroatranorin were identified in the
A. fuscata. In P. arseneana, we detected stictic acid, norstictic acid, usnic
acid and atranorin, while gyrophoric acid was not identified. Antioxidant
activity was evaluated by measuring the scavenging capacity of tested samples on
DPPH and superoxide anion radicals, reducing the power of samples and
determination of total phenolic compounds in extracts. As a result of the study,
gyrophoric acid was found to have the largest DPPH radical scavenging activity
with an IC50 value of 105.75 ug/ml. Moreover, the tested samples had an effective
superoxide anion radical scavenging and reducing power. The total content of
phenol in extracts was determined as pyrocatechol equivalent. The antimicrobial
activity was estimated by determination of the minimal inhibitory concentration
by the broth microdilution method. The most active was also gyrophoric acid, with
minimum inhibitory concentration values ranging from 0.019 to 1.25 mg/ml.
Anticancer activity was tested against LS174 (human colon carcinoma cell line),
A549 (human lung carcinoma cell line), Fem-x (malignant melanoma cell line), and
a chronic myelogeneous leukaemia K562 cell line using the MTT method. Extract of
P. arseneana expressed the strongest anticancer activity against all cell lines
with IC50 values ranging from 11.61 to 47.06 ug/ml.
PMID- 26417337
TI - Drosophila melanogaster - an embryonic model for studying behavioral and
biochemical effects of manganese exposure.
AB - Embryonic animals are especially susceptible to metal exposure. Manganese (Mn) is
an essential element, but in excess it can induce toxicity. In this study we used
Drosophila melanogaster as an embryonic model to investigate biochemical and
behavioral alterations due to Mn exposure. Flies were treated with standard
medium supplemented with MnCl2 at 0.1 mM, 0.5 mM or 1 mM from the egg to the
adult stage. At 0.5 mM and 1 mM Mn, newly ecloded flies showed significantly
enhanced locomotor activity when assessed by negative geotaxis behavior. In
addition, a significant increase in Mn levels (p < 0.0001) was observed, while
Ca, Fe, Cu, Zn and S levels were significantly decreased. A significant drop in
cell viability occurred in flies exposed to 1 mM Mn. There was also an induction
of reactive oxygen species at 0.5 mM and 1 mM Mn (p < 0.05). At 1 mM, Mn
increased Catalase (p < 0.005), Superoxide Dismutase (p < 0.005) and Hsp83 (p <
0.0001) mRNA expression, without altering Catalase or Superoxide Dismutase
activity; the activity of Thioredoxin reductase and Glutatione-S-transferase
enzymes was increased. Mn treatment did not alter ERK or JNK1/2 phosphorylation,
but at 1 mM caused an inhibition of p38(MAPK) phosphorylation. Together these
data suggest mechanisms of adaptation in the fly response to Mn exposure in
embryonic life.
PMID- 26417338
TI - Impact of urinary bladder cancer risk variants on prognosis and survival.
PMID- 26417340
TI - Biomarker: the universe of chemically induced gene expression alterations in
human hepatocyte.
PMID- 26417339
TI - Probing the origins of aromatase inhibitory activity of disubstituted coumarins
via QSAR and molecular docking.
AB - This study investigated the quantitative structure-activity relationship (QSAR)
of imidazole derivatives of 4,7-disubstituted coumarins as inhibitors of
aromatase, a potential therapeutic protein target for the treatment of breast
cancer. Herein, a series of 3,7- and 4,7-disubstituted coumarin derivatives (1
34) with R1 and R2 substituents bearing aromatase inhibitory activity were
modeled as a function of molecular and quantum chemical descriptors derived from
low-energy conformer geometrically optimized at B3LYP/6-31G(d) level of theory.
Insights on origins of aromatase inhibitory activity was afforded by the computed
set of 7 descriptors comprising of F10[N-O], Inflammat-50, Psychotic-80, H-047,
BELe1, B10[C-O] and MAXDP. Such significant descriptors were used for QSAR model
construction and results indicated that model 4 afforded the best statistical
performance. Good predictive performance were achieved as verified from the
internal (comprising the training and the leave-one-out cross-validation (LOO-CV)
sets) and external sets affording the following statistical parameters: R (2) Tr
= 0.9576 and RMSETr = 0.0958 for the training set; Q (2) CV = 0.9239 and RMSECV =
0.1304 for the LOO-CV set as well as Q (2) Ext = 0.7268 and RMSEExt = 0.2927 for
the external set. Significant descriptors showed correlation with functional
substituents, particularly, R1 in governing high potency as aromatase inhibitor.
Molecular docking calculations suggest that key residues interacting with the
coumarins were predominantly lipophilic or non-polar while a few were polar and
positively-charged. Findings illuminated herein serve as the impetus that can be
used to rationally guide the design of new aromatase inhibitors.
PMID- 26417341
TI - Cancer research: from prognostic genes to therapeutic targets.
PMID- 26417342
TI - Transcriptome based differentiation of harmless, teratogenetic and cytotoxic
concentration ranges of valproic acid.
PMID- 26417343
TI - The body-on-a-chip concept: possibilities and limitations.
PMID- 26417344
TI - The rediscovery of HepG2 cells for prediction of drug induced liver injury
(DILI).
PMID- 26417345
TI - Integrated spatiotemporal-metabolic modelling bridges the gap between metabolism
on the cellular level and organ function.
PMID- 26417346
TI - Concepts of predictive toxicology.
PMID- 26417347
TI - Human non-parenchymal liver cells for co-cultivation systems.
PMID- 26417348
TI - Molecular characterization of carotenoid biosynthetic genes and carotenoid
accumulation in Scutellaria baicalensis Georgi.
AB - Scutellaria baicalensis has a wide range of biological activities and has been
considered as an important traditional drug in Asia and North America for
centuries. A partial-length cDNA clone encoding phytoene synthase (SbPSY) and
full-length cDNA clonesencoding phytoene desaturase (SbPDS), xi-carotene
desaturase (SbZDS), beta-ring carotene hydroxylase (SbCHXB), and zeaxanthin
epoxidase (SbZEP)were identifiedin S. baicalensis. Sequence analyses revealed
that these proteins share high identity and conserved domains with their
orthologous genes. SbPSY, SbPDS, SbZDS, SbCHXB, and SbZEP were constitutively
expressed in the roots, stems, leaves, and flowers of S.b aicalensis. SbPSY,
SbPDS, and SbZDS were highly expressed in the stems, leaves, and flowers and
showed low expression in the roots, where only trace amounts of carotenoids were
detected. SbCHXB and SbZEP transcripts were expressed at relatively high levels
in the roots, stems, and flowers and were expressed at low levels in the leaves,
where carotenoids were mostly distributed. The predominant carotenoids in S.b
aicalensiswere lutein and beta-carotene, with abundant amounts found in the
leaves (517.19 and 228.37 MUg g(-1) dry weight, respectively). Our study on the
biosynthesis of carotenoids in S. baicalensis will provide basic data for
elucidating the contribution of carotenoids to the considerable medicinal
properties of S. baicalensis.
PMID- 26417349
TI - Dropwort (Filipendula hexapetala Gilib.): potential role as antioxidant and
antimicrobial agent.
AB - The aim of this study was to investigate the antioxidant activity of the
methanolic extracts of Filipendula hexapetala Gilib. aerial parts (FHA) and roots
(FHR) and their potential in different model systems, as well as antimicrobial
activity. According to this, a number of assays were employed to evaluate the
antioxidant and antimicrobial potential of F. hexapetala extracts. In addition,
the antioxidant activity assays in different model systems were carried out, as
well as pH, thermal and gastrointestinal stability studies. The phenolic
compounds contents in FHA and FHR were also determined. The results showed that
F. hexapetala extracts had considerable antioxidant activity in vitro and a great
stability in different conditions. The extracts exhibited antimicrobial activity
against most of the tested bacterial and fungal species. Also, the extracts
contain high level of phenolic compounds, especially aerial parts extract.
PMID- 26417350
TI - pH-sensitive, polymer modified, plasma stable niosomes: promising carriers for
anti-cancer drugs.
AB - The aim of this study was the design and evaluation of a novel plasma stable, pH
sensitive niosomal formulation of Mitoxantrone by a modified ethanol injection
method. Cholesterol hemisuccinate was added instead of cholesterol in order to
produce pH-sensitivity property and using PEG-Poly (monomethyl itaconate)-CholC6
(PEG-PMMI-CholC6) copolymer introduced simultaneously pH-sensitivity and plasma
stability properties in prepared niosomes. The pH-sensitivity and cytotoxicity of
Mitoxantrone niosomes were evaluated in vitro in phosphate buffer with different
pHs as well as using human ovarian cancer cell line (OVCAR-3), human breast
cancer cell line (MCF-7) and human umbilical vein endothelial cells (HUVEC).
Results showed that both cholesterol derivatives bearing formulations had pH
sensitive property and were found to release their contents under mild acidic
conditions rapidly. In addition, the PEG-PMMI-CholC6-based niosomes could reserve
the pH-sensitivity after incubation in plasma. Both Mitoxantrone-loaded pH
sensitive niosomes showed higher cytotoxicity than the conventional niosomes on
OVCAR-3 and MCF-7 cell lines. However, both pH-sensitive niosomes exhibited lower
cytotoxic effect on HUVEC cell line. Plasma stable, pH-sensitive niosomes could
improve the cytotoxic effect and reduce the side effects of anti-tumor drugs.
PMID- 26417351
TI - Butanolic fraction of Moringa oleifera Lam. (Moringaceae) attenuates isoprotrenol
induced cardiac necrosis and oxidative stress in rats: an EPR study.
AB - The preventive effect of Moringa oleifera polyphenolic fraction (MOPF) on cardiac
damage was evaluated in isoproterenol (ISO) induced cardiotoxicity model of
Wistar rats. Male rats in different groups were treated with MOPF orally at the
dose of 50, 100 and 150 mg/kg/day for 28 days and were subsequently administered
(s.c.) with ISO (85 mg/kg body weight) for the last two days. At the end of the
experiment levels of serum troponin-T, creatine kinase-MB, lactate dehydrogenase,
content of malondialdehyde (MDA), activities/levels of different cellular
antioxidants were estimated in control and experimental groups. Additionally,
scavenging potential to the hydroxyl radical of the fraction was measured by
electron paramagnetic resonance (EPR). ISO administered rats showed significant
increase in the levels of serum troponin-I, creatine kinase, lactate
dehydrogenase, and heart tissue MDA content. Furthermore, marked reduction in the
activities of antioxidants such as superoxide dismutase, catalase, glutathione
peroxidase and reduced glutathione levels were observed. EPR study showed an
increase in signal intensity in ISO-induced rats. Triphenyl tetrazolium chloride
(TTC) staining of heart section revealed a marked increase in infarcted area in
ISO-induced rats. Histological features of the heart also indicated a disruption
in the structure of cardiac myofibrils in these animals. MOPF (100 mg/kg body
weight) pretreatment prevented all these adverse effects of ISO. Present results
show that the rich polyphenolic content of Moringa oleifera significantly reduced
the myocardial damage and decreased the oxidative stress, possibly through
hydroxyl radical scavenging activity as evidenced from the EPR spectra.
PMID- 26417352
TI - Evaluation of offspring sex ratio, sex hormones and antioxidant enzymes following
exposure to methyl tertiary butyl ether in adult male Sprague-Dawley rats.
AB - Methyl tertiary butyl ether (MTBE) is an oxygenated fuel additive which has been
used widely in many parts of the world. This experiment was performed to
determine the effect of MTBE on offspring sex ratio, sex hormones and antioxidant
enzymes. A total of 20 adult Sprague-Dawley male rats were divided into four
groups and received 0, 400, 800 and 1600 mg/kg/day MTBE by gavages for 30
consecutive days. At the end of the experiment, blood samples were taken for
determination of sex hormones and antioxidant enzymes. Then, male rats were mated
with healthy unexposed female rats and sex of offspring was determined after
birth. Sex ratio was 0.48, 0.50, 0.43 and 0.50 in 0, 400, 800 and 1600 mg/kg/day
MTBE groups, respectively (P = 0.91). There was significant decreasing trend for
luteinizing hormone (LH) and testosterone in experimental groups (rs = -0.50, P =
0.030 and rs = -0.67, P = 0.002, respectively). No changes were observed for
superoxide dismutase. However, decrease in glutathione peroxidase (GPX) was
observed in all treatment groups compared with control which was significant in
400 mg/kg/day MTBE group (P = 0.016). The present study showed that paternal
exposure to oral MTBE has no effect on offspring sex ratio; while, MTBE exposure
could exert dose-dependent changes in serum testosterone and LH in treatment
groups. The results of the present study, need to be clarified in the future
studies.
PMID- 26417353
TI - Ruta montana L. leaf essential oil and extracts: characterization of bioactive
compounds and suppression of crown gall disease.
AB - The aims of this study were to assess the antimicrobial efficacy of the leaf
essential oil and the leaf extracts of R. montana against Botrytis cinerea,
Fusarium oxysporum, Verticillium dahliae, Aspergillus oryzae and Fusarium solani.
The oil (1.000 ug/disk) and the extracts (1.500 ug/disk) revealed a remarkable
antifungal effect against the tested plant pathogenic fungi with a radial growth
inhibition percentage of 40.0-80.0 % and 5.0-58.0 %, respectively along with
their respective MIC values ranging from 100 to 1100 ug/mL and 250 to 3000 ug/mL.
The oil had a strong detrimental effect on spore germination of all the tested
plant pathogens along with the concentration as well as time-dependent kinetic
inhibition of Fusarium oxysporum. Also, the oil exhibited a potent in vivo
antifungal effect against Botrytis cinerea on tomato plants. Experiments carried
out in plant revealed that the essential oil was slightly effective in
suppression of gall formation induced by Agrobacterium tumefaciens on bitter
almond. The results of this study indicate that the oil and extracts of R.
montana leaves could become natural alternatives to synthetic fungicides to
control certain important plant microbial diseases. The GC-MS analysis determined
that 28 compounds, which represented 89.03 % of total oil, were present in the
oil containing mainly 1-butene, methylcyclopropane, 2-butene and caryophyllene
oxide.
PMID- 26417354
TI - Rituximab therapy improves recalcitrant Pemphigus vulgaris.
AB - Pemphigus is a severe life-threatening blistering disease associated with
autoantibodies against cell adhesion proteins desmogleins 1 and 3. Patients with
severe pemphigus commonly show high rates of relapse after conventional
immunosuppressive therapy. The newly developed drug Rituximab showed impressing
promises in the treatment of refractory pemphigus vulgaris (PV). In the present
study the efficacy of a single course rituximab therapy in the treatment of PV
was investigated. Eighteen patients with severe recalcitrant PV were recruited to
this study. Pemphigus disease activity index (PDAI), anti-desmoglein 1 and anti
desmoglein 3 antibody titers, and percent of CD20 positive cells were measured at
baseline, 10 +/- 1, and 22 +/- 2 weeks after rituximab therapy. Rituximab was
given intravenously at dose 375 mg/m(2) once weekly for 4 weeks. Rituximab
therapy caused a dramatic reduction in the PDAI, accompanied by decreases in anti
desmoglein 1 and anti-desmoglein 3 antibody titers over the follow-up course. The
B-cell population decreased at the first follow-up, but returned to its baseline
levels at the second follow-up. Rituximab therapy decreased the dose of
immunosuppressive drugs required to control the disease. It seems that the
rituximab may be effective and safe for treatment of refractory PV.
PMID- 26417355
TI - Reduction of cytotoxicity of benzalkonium chloride and octenidine by Brilliant
Blue G.
AB - The irritative effects of preservatives found in ophthalmologic solution, or of
antiseptics used for skin disinfection is a consistent problem for the patients.
The reduction of the toxic effects of these compounds is desired. Brilliant Blue
G (BBG) has shown to meet the expected effect in presence of benzalkonium
chloride (BAK), a well known preservative in ophthalmic solutions, and octenidine
dihydrochloride (Oct), used as antiseptic in skin and wound disinfection. BBG
shows a significant protective effect on human corneal epithelial (HCE) cells
against BAK and Oct toxicity, increasing the cell survival up to 51 % at the
highest BAK or Oct concentration tested, which is 0.01 %, both at 30 min
incubation. Although BBG is described as a P2x7 receptor antagonist, other
selective P2x7 receptor antagonists, OxATP (adenosine 5'-triphosphate-2',3'
dialdehyde) and DPPH (N'-(3,5-dichloropyridin-4-yl)-3-phenylpropanehydrazide),
did not reduce the cytotoxicity of neither BAK nor Oct. Therefore we assume that
the protective effect of BBG is not due to its action on the P2x7 receptor.
Brilliant Blue R (BBR), a dye similar to BBG, was also tested for protective
effect on BAK and Oct toxicity. In presence of BAK no significant protective
effect was observed. Instead, with Oct a comparable protective effect was seen
with that of BBG. To assure that the bacteriostatic effect is not affected by the
combinations of BAK/BBG, Oct/BBG and Oct/BBR, bacterial growth inhibition was
analyzed on different Gram-negative and Gram-positive bacteria. All combinations
of BAK or Oct with BBG hinder growth of Gram-positive bacteria. The combinations
of 0.001 % Oct and BBR above 0.025 % do not hinder the growth of B. subtilis. For
Gram-negative bacteria, BBG and BBR reduce, but do not abolish, the antimicrobial
effect of BAK nor of Oct. In conclusion, the addition of BBG at bacterial
inhibitory concentrations is suggested in the ready-to-use ophthalmic
preparations and antiseptic solutions.
PMID- 26417356
TI - Evaluation on antioxidant properties of sixteen plant species from Jeju Island in
Korea.
AB - In this study, the antioxidant properties of 80 % ethanol extracts of 16 species
of plants from Jeju Island in Korea were evaluated using various antioxidant
assays, including the DPPH (1,1-Diphenyl-2-pricrylhydrazyl) radical scavenging,
superoxide scavenging, xanthine oxidase inhibition and hydrogen peroxide
scavenging activities. Among the 16 plant extracts tested, CN-13 showed strong
antioxidant properties in the DPPH radical scavenging and hydrogen peroxide
scavenging tests. The CN-13 ethanol extract was thus selected to be used for
further experiments, and was separated into various fractions using four
different organic solvents (n-hexane, methylene chloride, ethyl acetate and
butanol). The ethyl acetate fraction of CN-13 extract evidenced strong DPPH
radical scavenging properties as compared to the other fractions. The ethyl
acetate fraction also strongly inhibited DNA-damage induced by hydrogen peroxide
oxidative damage in a mouse lymphoma (L5178Y-R) cell line. Moreover, a
correlation between the total phenolic content of the extract, and its
antioxidant property was reported.
PMID- 26417357
TI - Biodegradation and detoxification of textile azo dyes by bacterial consortium
under sequential microaerophilic/aerobic processes.
AB - Release of textile azo dyes to the environment is an issue of health concern
while the use of microorganisms has proved to be the best option for remediation.
Thus, in the present study, a bacterial consortium consisting of Providencia
rettgeri strain HSL1 and Pseudomonas sp. SUK1 has been investigated for
degradation and detoxification of structurally different azo dyes. The consortium
showed 98-99 % decolorization of all the selected azo dyes viz. Reactive Black 5
(RB 5), Reactive Orange 16 (RO 16), Disperse Red 78 (DR 78) and Direct Red 81 (DR
81) within 12 to 30 h at 100 mg L(-1) concentration at 30 +/- 0.2 degrees C
under microaerophilic, sequential aerobic/microaerophilic and
microaerophilic/aerobic processes. However, decolorization under microaerophilic
conditions viz. RB 5 (0.26 mM), RO 16 (0.18 mM), DR 78 (0.20 mM) and DR 81 (0.23
mM) and sequential aerobic/microaerophilic processes viz. RB 5 (0.08 mM), RO 16
(0.06 mM), DR 78 (0.07 mM) and DR 81 (0.09 mM) resulted into the formation of
aromatic amines. In distinction, sequential microaerophilic/ aerobic process
doesn't show the formation of amines. Additionally, 62-72 % reduction in total
organic carbon content was observed in all the dyes decolorized broths under
sequential microaerophilic/aerobic processes suggesting the efficacy of method in
mineralization of dyes. Notable induction within the levels of azoreductase and
NADH-DCIP reductase (97 and 229 % for RB 5, 55 and 160 % for RO 16, 63 and 196 %
for DR 78, 108 and 258 % for DR 81) observed under sequential
microaerophilic/aerobic processes suggested their critical involvements in the
initial breakdown of azo bonds, whereas, a slight increase in the levels of
laccase and veratryl alcohol oxidase confirmed subsequent oxidation of formed
amines. Also, the acute toxicity assay with Daphnia magna revealed the nontoxic
nature of the dye-degraded metabolites under sequential microaerophilic/aerobic
processes. As biodegradation under sequential microaerophilic/aerobic process
completely detoxified all the selected textile azo dyes, further efforts should
be made to implement such methods for large scale dye wastewater treatment
technologies.
PMID- 26417358
TI - Effect of Momordica charantia fruit extract on vascular complication in type 1
diabetic rats.
AB - Diabetes mellitus is one of the risk factors in the development of vascular
complications. Decreased nitric oxide (NO) production and increased lipid
peroxidation in diabetes mellitus are the dominant exaggerating factors.
Mormodica charantia (MC) was proven to be useful in improving diabetes mellitus
and its complications. In the present study, a total of 40 male Sprague-Dawley
rats were used. Diabetes was induced by a single dose (50 mg/kg) of
streptozotocin (STZ), intramuscularly. Following 4 weeks of STZ induction, the
animals were equally divided into five groups (n = 8); Control group (Ctrl),
control group treated with MC (Ctrl-MC), diabetic untreated group (DM-Ctrl),
diabetic group treated with MC (DM-MC) and diabetic group treated with metformin
150 g/kg (DM-Met). Oral administration of the MC fruit extract (1.5 g/kg) was
continued for 28 days. DM-MC group showed a significant decrease (P < 0.05) in
blood pressure, total cholesterol and triglyceride levels compared to the DM-Ctrl
group. Aortic tissue NO level was significantly increased and malondialdehyde
level was decreased in the DM-MC group. Immunohistochemical staining showed an
increase in eNOS expression in the endothelial lining of the DM-MC group.
Similarly, morphological deterioration of the aortic tissues was reverted to
normal. In summary, treatment with the MC fruit extract exerted the significant
vasculoprotective effect in the type 1 diabetic rat model.
PMID- 26417359
TI - Chemical composition of biomass generated in the guava tree pruning.
AB - Psidium guajava L. (Myrtaceae) is a native plant of Central America and is now
widely cultivated in many tropical regions of the world for the fruit production.
In Mexico, in the guava orchards common practices to control fruit production
are: water stress, defoliation and pruning. In this study, we report the chemical
composition of the biomass (branches and leaves) generated in the pruning
practices. The results ranged as follows: pH (4.98-5.88), soda solubility (39.01
70.49 %), ash (1.87-8.20 %); potassium and calcium were the major inorganic
elements in ash. No heavy metals were detected in the studied samples; total
solubility (15.21-46.60 %), Runkel lignin (17.77-35.26 %), holocellulose (26.56
69.49 %), alpha-cellulose (15.53-35.36 %), hemicelluloses (11.02-34.12 %),
tannins in aqueous extracts (3.81-9.06 %), and tannins in ethanolic extracts
(3.42-15.24 %).
PMID- 26417360
TI - Comparative growth analysis of capsulated (Vi+) and acapsulated (Vi-) Salmonella
typhi isolates in human blood.
AB - Salmonella enterica serovar Typhi (S. Typhi) is a human restricted pathogen. It
biosynthesizes a virulence capsular polysaccharide named as Vi antigen. S. Typhi
regulates expression of genes involved in the biosynthesis of Vi antigen in
response to osmolarity. Beside Vi-positive isolates, Vi-negative (acapsulated)
isolates are also pathogenic. However, Vi-positive isolates are more prevalent.
The present study was planned to investigate comparative growth of Vi-positive
and Vi-negative S. Typhi isolates in an ex vivo human whole blood model. Four
isolates of each type were tested for growth in human whole blood and in an
enrichment medium (Tryptic soy broth-TSB) as a control. It was found that
capsulated (Vi-positive) strains formed smooth circular colonies and grew with
shorter lag and generation time than Vi-negative isolates. Overall growth pattern
of S. Typhi isolates both in vitro and ex vivo conditions showed that Vi-positive
isolates grew at a faster rate. Especially in human blood, the lag time of
acapsulated isolates was almost doubled as compared to capsulated S. Typhi
isolates. It was also observed that Vi-negative isolates reduced in number up to
81 % during the first 12 hours of incubation in human whole blood. Interestingly,
both types of isolates had similar growth curve in TSB indicating that Vi capsule
is dispensable for bacterial growth in vitro. This study shows for the first time
that absence of capsular antigen retards the growth of Vi-negative isolates on
initial contact with human blood, but with passage of time they adjust themselves
according to the new environment.
PMID- 26417361
TI - The effect of high intensity interval training on cardioprotection against
ischemia-reperfusion injury in wistar rats.
AB - The aims of the present study were to determine whether short term high intensity
interval training (HIIT) could protect the heart against ischemia reperfusion
(IR) injury; and if so, to evaluate how long the exercise-associated protection
can be lasted. Sixty-three rats were randomly assigned into sedentary (n = 15),
sham (n = 7), and exercise groups (n = 41). Rats in the exercise groups performed
5 consecutive days of HIIT on treadmill: 5 min warm up with 50 % VO2max, 6*2 min
with 95-105 % VO2max (about 40 to 45 m/min), 5*2 min recovery with 65-75 % VO2max
(about 28 to 32 m/min), and 3 min cool down with 50 % VO2max, all at 0 % grade.
Animals exposed to an in vivo cardiac IR surgery, performed at days 1, 7, and 14
following the final exercise session. Ischemia-induced arrhythmias, myocardial
infarct size (IS), plasma lactate dehydrogenase (LDH) and creatine kinase (CK)
activities were measured in all animals. Compared to sedentary rats, exercised
animals sustained less IR injury as evidenced by a lower size of infarction and
lower levels of LDH and CK at day one and day 7 post exercise. In comparison of
sedentary group, IS significantly decreased in EX-IR1 and EX-IR7 groups (50 and
35 %, respectively), but not in EX-IR14 group (19 %). The exercise-induced
cardioprotection disappeared 14 days following exercise cessation. There were no
significant changes in ischemia-induced arrhythmia between exercised and
sedentary rats. The results clearly demonstrate that HIIT protects the heart
against myocardial IR injury. This protective effect can be sustained for at
least one week following the cessation of the training.
PMID- 26417362
TI - The phycobilisomes: an early requisite for efficient photosynthesis in
cyanobacteria.
AB - Cyanobacteria trap light energy by arrays of pigment molecules termed
"phycobilisomes (PBSs)", organized proximal to "reaction centers" at which
chlorophyll perform the energy transduction steps with highest quantum
efficiency. PBSs, composed of sequential assembly of various chromophorylated
phycobiliproteins (PBPs), as well as nonchromophoric, basic and hydrophobic
polypeptides called linkers. Atomic resolution structure of PBP is a heterodimer
of two structurally related polypeptides but distinct specialised polypeptides- a
and beta, made up of seven alpha-helices each which played a crucial step in
evolution of PBPs. PBPs carry out various light dependent responses such as
complementary chromatic adaptation. The aim of this review is to summarize and
discuss the recent progress in this field and to highlight the new and the
questions that remain unresolved.
PMID- 26417363
TI - A sulfated polysaccharide of Ecklonia cava inhibits the growth of colon cancer
cells by inducing apoptosis.
AB - We investigated anticancer effects of the crude polysaccharides (CPs) isolated
from Ecklonia cava enzymatic extracts using AMG, Viscozyme, Protamex, and
Alcalase enzyme against a colon cancer cell line, CT26 cells. Among them, the CP
of Protamex extract (PCP) contained the highest fucose and sulfated group
contents and showed the highest growth inhibitory effect against CT-26 cells. In
addition, PCP dose-dependently increased the formation of apoptotic body and the
percentage of Sub-G1 DNA contents. Also, PCP activated caspase 9 and PARP as
regulating the expressions of Bax and Bcl-2. Moreover, PPP2, a fraction purified
from PCP showed the highest growth inhibitory effect against CT 26 cells with the
increased fucose and sulfated group contents. The results demonstrate that the
isolated SP containing plentiful fucose and sulfated group contents has the
anticancer effect on colon cancer cells via regulation of Bcl-2/Bax signal
pathway.
PMID- 26417364
TI - Paper-based acetylcholinesterase inhibition assay combining a wet system for
organophosphate and carbamate pesticides detection.
AB - A dramatic increase in pesticide usage in agriculture highlights the need for on
site monitoring for public health and safety. Here, a paper-based sensor combined
with a wet system was developed for the simple and rapid screening of
organophosphate (OP) and carbamate (CM) pesticides based on the inhibition of
acetylcholinesterase (AChE). The paper-based sensor was designed as a foldable
device consisting of a cover and detection sheets pre-prepared with indoxyl
acetate and AChE, respectively. The paper-based sensor requires only the
incubation of a sample on the test zone for 10 minutes, followed by closing of
the foldable sheet to initiate the enzymatic reaction. Importantly, the buffer
loading hole was additionally designed on the cover sheet to facilitate the
interaction of the coated substrate and the immobilized enzyme. This subsequently
facilitates the mixing of indoxyl acetate with AChE, resulting in the improved
analytical performance of the sensor. The absence or decrease in blue color
produced by the AChE hydrolysis of indoxyl acetate can be observed in the
presence of OPs and CMs. Under optimized conditions and using image analysis, the
limit of detection (LOD) of carbofuran, dichlorvos, carbaryl, paraoxon, and
pirimicarb are 0.003, 0.3, 0.5, 0.6, and 0.6 ppm, respectively. The assay could
be applied to determine OP and CM residues in spiked food samples. Visual
interpretation of the color signal was clearly observed at the concentration of 5
mg/kg. Furthermore, a self-contained sample pre-concentration approach greatly
enhanced the detection sensitivity. The paper-based device developed here is low
cost, requires minimal reagents and is easy to handle. As such, it would be
practically useful for pesticide screening by non-professional end-users.
PMID- 26417365
TI - Growth, physiology and yield of durum wheat (Triticum durum) treated with sewage
sludge under water stress conditions.
AB - In arid and semi-arid areas, low soil fertility and water deficit considerably
limit crop production. The use of sewage sludge as an organic amendment could
contribute to the improvement of soil fertility and hence the agronomic
production. The study aims to highlight the behaviour of durum wheat to the
application of sewage sludge associated with water stress. The assessment focused
on morphophysiological parameters of the wheat plant and yield. Under greenhouse
conditions, the variety Mohamed Ben Bachir was treated by four water stress
levels (100 %, 80 %, 50 % and 30 %). Each stress level comprised five fertilizer
treatments: 20, 50 and 100 t/ha of dry sludge, 35 kg/ha of urea, and a control
with no fertilization. Results revealed a significant loss in water content and
chlorophyll a in leaves. Water stress negatively affected the development of
wheat plants by reducing significantly seed yield, leaf area and biomass
produced. Plant's responses to water stress manifested by an accumulation of
proline and a decrease in total phosphorus. However, the increasing doses of
sewage sludge limited the effect of water stress. Our findings showed an increase
in the amount of chlorophyll pigments, leaf area, total phosphorus, biomass and
yield. In addition, excessive accumulation of proline (1.11 +/- 1.03 ug/g DM) was
recorded as a result of the high concentration of sludge (100 t/ha DM). The
application of sewage sludge is beneficial for the wheat crop, but the high
accumulation of proline in plants treated with high dose of sludge suggests to
properly consider this fact. The application of sludge should be used with
caution in soils where water is limited. Because the combined effect of these two
factors could result in a fatal osmotic stress to crop development.
PMID- 26417366
TI - Blood pressure percentiles by age and body mass index for adults.
AB - Since no comprehensive study has been conducted on blood pressure (BP)
percentiles established upon nationally representative sample population of
adults, the present study aimed to construct the blood pressure percentiles by
age, sex and body mass index (BMI) of the subjects. Analyses were based on data
collected in 2011 from 8,425 adults aged 25 to 69 years old. Data on demographic
characteristics, anthropometric measurements, and blood pressure was recorded for
each subject. Linear Regression analysis was used to assess the adjusted
relationship of age-sex-specific standard deviation scores of BMI, height, and
weight with blood pressure. Four separate models for systolic blood pressure
(SBP) and diastolic blood pressure (DBP) of men and women were constructed for BP
percentiles according to age and BMI. Blood pressure increased with the rise in
BMI and weight, but showed a negative correlation with height. SBP and DBP rose
steadily with increasing age, but the rise in SBP was greater than DBP.
Overweight and obese population, seem to fall into the category of hypertensive.
The findings of present study show that BP percentiles are steadily increased by
age and BMI. In addition, most obese or overweight adults are hypertensive.
PMID- 26417367
TI - A Multilayer Naive Bayes Model for Analyzing User's Retweeting Sentiment
Tendency.
AB - Today microblogging has increasingly become a means of information diffusion via
user's retweeting behavior. Since retweeting content, as context information of
microblogging, is an understanding of microblogging, hence, user's retweeting
sentiment tendency analysis has gradually become a hot research topic. Targeted
at online microblogging, a dynamic social network, we investigate how to exploit
dynamic retweeting sentiment features in retweeting sentiment tendency analysis.
On the basis of time series of user's network structure information and published
text information, we first model dynamic retweeting sentiment features. Then we
build Naive Bayes models from profile-, relationship-, and emotion-based
dimensions, respectively. Finally, we build a multilayer Naive Bayes model based
on multidimensional Naive Bayes models to analyze user's retweeting sentiment
tendency towards a microblog. Experiments on real-world dataset demonstrate the
effectiveness of the proposed framework. Further experiments are conducted to
understand the importance of dynamic retweeting sentiment features and temporal
information in retweeting sentiment tendency analysis. What is more, we provide a
new train of thought for retweeting sentiment tendency analysis in dynamic social
networks.
PMID- 26417368
TI - On Training Efficiency and Computational Costs of a Feed Forward Neural Network:
A Review.
AB - A comprehensive review on the problem of choosing a suitable activation function
for the hidden layer of a feed forward neural network has been widely
investigated. Since the nonlinear component of a neural network is the main
contributor to the network mapping capabilities, the different choices that may
lead to enhanced performances, in terms of training, generalization, or
computational costs, are analyzed, both in general-purpose and in embedded
computing environments. Finally, a strategy to convert a network configuration
between different activation functions without altering the network mapping
capabilities will be presented.
PMID- 26417369
TI - Changes in Bone Mineral Density and Metabolic Parameters after Pulsatile
Gonadorelin Treatment in Young Men with Hypogonadotropic Hypogonadism.
AB - To assess the prevalence of osteoporosis in young men with hypogonadotropic
hypogonadism (HH) and to investigate the changes of BMD and metabolic parameters,
a total of 22 young male patients with HH and 20 healthy controls were enrolled
in the study. BMD, biochemical, and hormonal parameters were measured in two
groups. Osteoporosis was more prevalent in HH patients (45.45%) than the control
subjects (10.00%) (P < 0.001). The patients with HH had lower BMD in lumbar spine
2-4, femoral neck, and total hip (P < 0.001, for all) and higher fasting insulin
(P = 0.001), HOMA-IR (P = 0.002), and SHBG (P < 0.001) compared to the controls.
After 6 months of pulsatile gonadorelin treatment, BMI (P = 0.021) and BMD in
lumbar spine 2-4, femoral neck, and total hip (P = 0.002, P = 0.003, and P =
0.003, resp.) increased dramatically and total cholesterol (P = 0.034), fasting
insulin (P = 0.025), HOMA-IR (P = 0.021), and SHBG (P = 0.001) decreased
significantly in HH patients. The study shows a higher prevalence of osteoporosis
in young men with HH. Long-term pulsatile gonadorelin treatment indicates a
positive effect on BMD and metabolic parameters of HH patients.
PMID- 26417370
TI - Evaluation of AgNORs in Oral Potentially Malignant Lesions.
AB - Oral squamous cell carcinoma (OSCC) is usually preceded by detectable mucosal
changes, as leukoplakias and erythroplakia. Histologically, these lesions can
range from hyperkeratosis and acanthosis to epithelial dysplasia and even OSCC.
The aim of this study was to investigate the proliferative activity, using AgNORs
quantification proteins, in low- and high-risk oral epithelial dysplasia, OSCC,
and nondysplastic epithelium (inflammatory fibrous hyperplasia). The sample was
divided into 4 groups: G1: 10 cases of inflammatory fibrous hyperplasia (IFH),
G2: 11 cases of low-risk epithelial dysplasia (LD), G3: 10 cases of high-risk
epithelial dysplasia (HD), and G4: 11 cases of OSCC. The quantitative analysis
was performed using an image processing software in photomicrographs at 1000x
magnification. The one-way ANOVA was used for comparison of the mean AgNORs
counts between the study groups. The mean AgNORs count was significantly higher
(P <= 0.01) in OSCC when compared to IFH and the LD; however, it was not
statistically different from HD. The mean number of LD was significantly lower
than the HD and OSCC, with no difference related to IFH. AgNORs quantification
can be an important and cheap method to help in the determination of the degree
of epithelial dysplasia and, consequently, in the analysis of their potential for
malignant transformation.
PMID- 26417371
TI - Phenotypic and Molecular Characterisation of Extended-Spectrum Beta-Lactamase
Producing Escherichia coli Obtained from Animal Fecal Samples in Ado Ekiti,
Nigeria.
AB - Production of extended-spectrum beta-lactamases (ESBLs) producing E. coli in
animals and different methods of identifications from Ado Ekiti, Ekiti State,
Nigeria, were investigated. Three hundred and fifty fecal samples, collected from
apparently healthy cattle and pigs, were cultured and identified following
standard procedures. ESBL phenotypic detection was carried out using combination
disc test, double disc synergism test, and ESBL brilliance agar screening.
Molecular detection of TEM, SHV, and CTX-M genes was carried out using standard
molecular method. One hundred and fourteen E. coli isolates were recovered from
the 350 samples processed, out of which 72 (63.2%) isolates were positive for
ESBLs with multiple resistance to the antibiotics used. Eighty-one (71%) isolates
were positive for ESBL by combination disc test, 90 (78.9%) were positive for
double disc synergism test, and 93 (81.6%) were positive for ESBL brilliance
agar. TEM and CTX-M genes were detected in 48 (42.1%) and 51 (44.7%) isolates,
respectively. SHV gene was not detected in any of the isolates while TEM and CTX
M were detected in 33 (28.9%) isolates. This study showed high resistance of E.
coli to antibiotics, particularly to the third generation cephalosporins. Regular
monitoring and regulated use of antibiotics in livestock should be encouraged.
PMID- 26417372
TI - Topical Hypericum perforatum Improves Tissue Regeneration in Full-Thickness
Excisional Wounds in Diabetic Rat Model.
AB - Delayed wound healing process is one of the most important concerns in diabetes.
Healing of wounds has four phases, namely, hemostasis, inflammation,
proliferation, and remodeling. For a successful repair, all four factors must
occur properly. Hence, we aimed to evaluate the healing effects of Hypericum
perforatum (HP) on full-thickness diabetic skin wounds by using stereological
methods. Forty-eight female diabetic rats were randomly divided into four groups
(n = 12): gel base treated group, HP 5% gel treated group, HP 10% gel treated
group, and the control group which received no treatment. A circular 1 cm(2) full
thickness wound was created on the animal's neck and wound area was measured
every three days. After sacrificing the animals, skin samples were fixed and
prepared for stereological evaluations. Based on the results, HP treated group
showed faster wound closure rate in comparison with control and vehicle groups (P
< 0.05). In addition, numerical density of fibroblasts, volume density of
collagen bundles, and mean diameter and volume densities of the vessels in HP
group were significantly higher than control and vehicle groups. The results of
this study showed that HP has the ability to improve tissue regeneration by
enhancing fibroblast proliferation, collagen bundle synthesis, and
revascularization.
PMID- 26417373
TI - Acupoint Catgut Embedding for Obesity: Systematic Review and Meta-Analysis.
AB - Acupoint catgut embedding (ACE) was applied widely to antiweight in China. The
aim of this review is to estimate the effectiveness and safety of ACE on obesity.
A literature search was conducted in PubMed, Cochrane Library, EBASE, CNKI, and
so forth, using combination subject terms of obesity (or overweight, weight loss,
etc.) and acupoint catgut embedding (or catgut implantation, catgut embedding).
Improvement rate, reduction of body weight and body mass index (BMI), and so
forth were analyzed. 43 studies were included for systematic review and meta
analysis. Although with poor methodological quality, ACE was superior to manual
acupuncture (MA), sham, and cupping in improvement rate and presented a better
tendency (OR > 1) compared with drugs and electroacupuncture (EA). Mean values of
weight loss by ACE were 1.14 kg, 1.26 kg, 1.79 kg, and 3.01 kg comparing with MA,
drugs, EA, and sham, respectively. Mean of BMI reduced to 0.56 kg/m(2), 0.83
kg/m(2), 0.79 kg/m(2), and 1.63 kg/m(2) comparing with MA, drugs, EA, and sham.
Less adverse effects were reported. Pooled outcomes presented a tendency of equal
or superior effects to other interventions and fewer side effects. Future high
quality trials with rigorous design and positive FDA approved drug as control are
urgent to assess the effect of ACE for obesity. PROSPERO registration number is
as follows: CRD42015016006.
PMID- 26417374
TI - Effect of Tongxinluo on Nephrin Expression via Inhibition of Notch1/Snail Pathway
in Diabetic Rats.
AB - Podocyte injury is an important mechanism of diabetic nephropathy (DN).
Accumulating evidence suggests that nephrin expression is decreased in podocyte
in DN. Moreover, it has been demonstrated that tongxinluo (TXL) can ameliorate
renal structure disruption and dysfunction in DN. However, the effect of TXL on
podocyte injury in DN and its molecular mechanism is unclear. In order to explore
the effect of TXL on podocyte injury and its molecular mechanism in DN, our in
vivo and in vitro studies were performed. Our results showed that TXL increased
nephrin expression in diabetic rats and in high glucose cultured podocyte.
Meanwhile, TXL decreased ICN1 (the intracellular domain of notch), HES1, and
snail expression in podocyte in vivo and in vitro. More importantly, we found
that TXL protected podocyte from injury in DN. The results demonstrated that TXL
inhibited the activation of notch1/snail pathway and increased nephrin
expression, which may be a mechanism of protecting effect on podocyte injury in
DN.
PMID- 26417375
TI - Design and Formulation of Optimized Microemulsions for Dermal Delivery of
Resveratrol.
AB - The objective of this study was to formulate optimal formulations of
microemulsions (MEs) and evaluate their feasibility for delivery of resveratrol
into human skin ex vivo. Oil-in-water MEs were formulated using surfactant (S)
PEG-8 caprylic/capric glycerides and cosurfactant (CoS) polyglyceryl-6
isostearate. Ethyl oleate was used as an oily phase. MEs were formulated using 5
: 1, 6 : 1, and 7 : 1 surfactant and cosurfactant (S : CoS) weight ratios.
Pseudoternary phase diagrams were constructed and optimal compositions of MEs
were obtained using Design Expert software. Mean droplet size for optimized ME
formulations was determined to be 68.54 +/- 1.18 nm, 66.08 +/- 0.16 nm, and 66.66
+/- 0.56 nm for systems with S : CoS weight ratios 5 : 1, 6 : 1, and 7 : 1,
respectively. Resveratrol loading resulted in mean droplet size increase. The
distribution of droplet size between fractions changed during storage of
formulated MEs. Results demonstrated the increase of number of droplets and
relative surface area when S : CoS weight ratios were 6 : 1 and 7 : 1 and the
decrease when S : CoS weight ratio was 5 : 1. The highest penetration of
resveratrol into the skin ex vivo was determined from ME with S : CoS weight
ratio 5 : 1. It was demonstrated that all MEs were similar in their ability to
deliver resveratrol into the skin ex vivo.
PMID- 26417376
TI - Bone Mineral Density and Fracture Risk Assessment to Optimize Prosthesis
Selection in Total Hip Replacement.
AB - The variability in patient outcome and propensity for surgical complications in
total hip replacement (THR) necessitates the development of a comprehensive,
quantitative methodology for prescribing the optimal type of prosthetic stem:
cemented or cementless. The objective of the research presented herein was to
describe a novel approach to this problem as a first step towards creating a
patient-specific, presurgical application for determining the optimal prosthesis
procedure. Finite element analysis (FEA) and bone mineral density (BMD)
calculations were performed with ten voluntary primary THR patients to estimate
the status of their operative femurs before surgery. A compilation model of the
press-fitting procedure was generated to define a fracture risk index (FRI) from
incurred forces on the periprosthetic femoral head. Comparing these values to
patient age, sex, and gender elicited a high degree of variability between
patients grouped by implant procedure, reinforcing the notion that age and gender
alone are poor indicators for prescribing prosthesis type. Additionally,
correlating FRI and BMD measurements indicated that at least two of the ten
patients may have received nonideal implants. This investigation highlights the
utility of our model as a foundation for presurgical software applications to
assist orthopedic surgeons with selecting THR prostheses.
PMID- 26417377
TI - Parametric Modeling of Human Gradient Walking for Predicting Minimum Energy
Expenditure.
AB - A mathematical model to predict the optimum gradient for a minimum energetic cost
is proposed, based on previous results that showed a minimum energetic cost when
gradient is -10%. The model focuses on the variation in mechanical energy during
gradient walking. It is shown that kinetic energy plays a marginal role in low
speed gradient walking. Therefore, the model considers only potential energy. A
mathematical parameter that depends on step length was introduced, showing that
the optimal gradient is a function of that parameter. Consequently, the optimal
negative gradient depends on the individual step length. The model explains why
recent results do not suggest a single optimal gradient but rather a range around
-10%.
PMID- 26417378
TI - Review of Modelling Techniques for In Vivo Muscle Force Estimation in the Lower
Extremities during Strength Training.
AB - BACKGROUND: Knowledge of the musculoskeletal loading conditions during strength
training is essential for performance monitoring, injury prevention,
rehabilitation, and training design. However, measuring muscle forces during
exercise performance as a primary determinant of training efficacy and safety has
remained challenging. METHODS: In this paper we review existing computational
techniques to determine muscle forces in the lower limbs during strength
exercises in vivo and discuss their potential for uptake into sports training and
rehabilitation. RESULTS: Muscle forces during exercise performance have almost
exclusively been analysed using so-called forward dynamics simulations, inverse
dynamics techniques, or alternative methods. Musculoskeletal models based on
forward dynamics analyses have led to considerable new insights into muscular
coordination, strength, and power during dynamic ballistic movement activities,
resulting in, for example, improved techniques for optimal performance of the
squat jump, while quasi-static inverse dynamics optimisation and EMG-driven
modelling have helped to provide an understanding of low-speed exercises.
CONCLUSION: The present review introduces the different computational techniques
and outlines their advantages and disadvantages for the informed usage by
nonexperts. With sufficient validation and widespread application, muscle force
calculations during strength exercises in vivo are expected to provide
biomechanically based evidence for clinicians and therapists to evaluate and
improve training guidelines.
PMID- 26417380
TI - Deformation of Soft Tissue and Force Feedback Using the Smoothed Particle
Hydrodynamics.
AB - We study the deformation and haptic feedback of soft tissue in virtual surgery
based on a liver model by using a force feedback device named PHANTOM OMNI
developed by SensAble Company in USA. Although a significant amount of research
efforts have been dedicated to simulating the behaviors of soft tissue and
implementing force feedback, it is still a challenging problem. This paper
introduces a kind of meshfree method for deformation simulation of soft tissue
and force computation based on viscoelastic mechanical model and smoothed
particle hydrodynamics (SPH). Firstly, viscoelastic model can present the
mechanical characteristics of soft tissue which greatly promotes the realism.
Secondly, SPH has features of meshless technique and self-adaption, which supply
higher precision than methods based on meshes for force feedback computation.
Finally, a SPH method based on dynamic interaction area is proposed to improve
the real time performance of simulation. The results reveal that SPH methodology
is suitable for simulating soft tissue deformation and force feedback
calculation, and SPH based on dynamic local interaction area has a higher
computational efficiency significantly compared with usual SPH. Our algorithm has
a bright prospect in the area of virtual surgery.
PMID- 26417379
TI - Comparative Sensitivity Analysis of Muscle Activation Dynamics.
AB - We mathematically compared two models of mammalian striated muscle activation
dynamics proposed by Hatze and Zajac. Both models are representative for a broad
variety of biomechanical models formulated as ordinary differential equations
(ODEs). These models incorporate parameters that directly represent known
physiological properties. Other parameters have been introduced to reproduce
empirical observations. We used sensitivity analysis to investigate the influence
of model parameters on the ODE solutions. In addition, we expanded an existing
approach to treating initial conditions as parameters and to calculating second
order sensitivities. Furthermore, we used a global sensitivity analysis approach
to include finite ranges of parameter values. Hence, a theoretician striving for
model reduction could use the method for identifying particularly low
sensitivities to detect superfluous parameters. An experimenter could use it for
identifying particularly high sensitivities to improve parameter estimation.
Hatze's nonlinear model incorporates some parameters to which activation dynamics
is clearly more sensitive than to any parameter in Zajac's linear model. Other
than Zajac's model, Hatze's model can, however, reproduce measured shifts in
optimal muscle length with varied muscle activity. Accordingly we extracted a
specific parameter set for Hatze's model that combines best with a particular
muscle force-length relation.
PMID- 26417381
TI - Kinematic, Dynamic, and Energy Characteristics of Diastolic Flow in the Left
Ventricle.
AB - Blood flow characteristics in the normal left ventricle are studied by using the
magnetic resonance imaging, the Navier-Stokes equations, and the work-energy
equation. Vortices produced during the mitral valve opening and closing are
modeled in a two-dimensional analysis and correlated with temporal variations of
the Reynolds number and pressure drop. Low shear stress and net pressures on the
mitral valve are obtained for flow acceleration and deceleration. Bernoulli
energy flux delivered to blood from ventricular dilation is practically balanced
by the energy influx and the rate change of kinetic energy in the ventricle. The
rates of work done by shear and energy dissipation are small. The dynamic and
energy characteristics of the 2D results are comparable to those of a 3D model.
PMID- 26417382
TI - Assessment of Knee Cartilage Stress Distribution and Deformation Using Motion
Capture System and Wearable Sensors for Force Ratio Detection.
AB - Knowledge about the knee cartilage deformation ratio as well as the knee
cartilage stress distribution is of particular importance in clinical studies due
to the fact that these represent some of the basic indicators of cartilage state
and that they also provide information about joint cartilage wear so medical
doctors can predict when it is necessary to perform surgery on a patient. In this
research, we apply various kinds of sensors such as a system of infrared cameras
and reflective markers, three-axis accelerometer, and force plate. The
fluorescent marker and accelerometers are placed on the patient's hip, knee, and
ankle, respectively. During a normal walk we are recording the space position of
markers, acceleration, and ground reaction force by force plate. Measured data
are included in the biomechanical model of the knee joint. Geometry for this
model is defined from CT images. This model includes the impact of ground
reaction forces, contact force between femur and tibia, patient body weight,
ligaments, and muscle forces. The boundary conditions are created for the finite
element method in order to noninvasively determine the cartilage stress
distribution.
PMID- 26417383
TI - Intracellular microlasers.
AB - Optical microresonators1 which confine light within a small cavity are widely
exploited for various applications ranging from the realization of lasers2 and
nonlinear devices3, 4, 5 to biochemical and optomechanical sensing6, 7, 8, 9, 10,
11. Here we employ microresonators and suitable optical gain materials inside
biological cells to demonstrate various optical functions in vitro including
lasing. We explored two distinct types of microresonators: soft and hard, that
support whispering-gallery modes (WGM). Soft droplets formed by injecting oil or
using natural lipid droplets support intracellular laser action. The laser
spectra from oil-droplet microlasers can chart cytoplasmic internal stress (~500
pN/MUm2) and its dynamic fluctuations at a sensitivity of 20 pN/MUm2 (20 Pa). In
a second form, WGMs within phagocytized polystyrene beads of different sizes
enable individual tagging of thousands of cells easily and, in principle, a much
larger number by multiplexing with different dyes.
PMID- 26417384
TI - Emerging Trends in Behavioral Genetic Studies of Child Temperament.
AB - In this article, we describe three emerging trends in the application of
behavioral genetic methods to the study of temperament. The trends-using multiple
methods to assess temperament, considering contextual influences on temperament,
and evaluating the structure of temperament-have been well studied in the
phenotypic literature, but adding a behavioral genetic perspective can enrich our
understanding of temperament. We review recent behavioral genetic research in
each of these areas and discuss its implications.
PMID- 26417385
TI - Rural-urban differences in the clinico-pathologic profiles of Jamaican men with
prostate cancer.
AB - BACKGROUND: Prostate cancer causes the highest number of cancer-related deaths in
Jamaican men. It is not known whether rural-dwelling men present with worse
disease than urban-dwelling men at initial presentation. Since rural and urban
dwelling Jamaicans are predominantly of African descent and generally similar in
respect of racial composition, if any significant variation in initial
presentation were found, it would suggest that these are likely due to
differences in awareness, access to care, and screening patterns. METHODS: The
medical records of rural and urban-dwelling patients with prostate cancer were
compared. Patients' age at presentation, initial prostate-specific antigen level,
digital rectal examination findings, biopsy Gleason scores and initial treatment
received were compared using bivariate and logistic regression analyses. RESULTS:
In unadjusted analyses rural-dwelling men were older compared to urban-dwelling
men (72 years versus 68.5 years, p = 0.035), had higher median PSA values (22.9
ng/ml versus 18 ng/ml, p = 0.001), higher local tumour stage (65.2 % versus 34.8
% T3 disease; 73.7 % versus 26.3 % T4 disease; p = 0.005), higher mean Gleason
scores (p = 0.048) and more non-curative initial treatments. Local tumour stage
was the only statistically significant difference between rural and urban
dwelling men in logistic regression analysis with rural-dwelling men having a 70
% higher risk of locally-advanced disease (OR = 1.70, 95 % CI: 1.03-2.79; p =
0.038). CONCLUSION: Rural-dwelling men presented with more advanced prostate
cancer compared to urban-dwelling men. As both rural and urban-dwelling men are
of predominant African descent it is likely that these differences are due to
differences in access to care, screening practice and awareness of the disease.
PMID- 26417386
TI - Human papillomavirus types in non-cervical high-grade intraepithelial neoplasias
and invasive carcinomas from San Luis Potosi, Mexico: a retrospective cross
sectional study.
AB - BACKGROUND: Viral infections and the burden of high-grade intraepithelial
neoplasias (HIN) and invasive carcinomas (IC) associated to infections by human
papillomavirus (HPV) types may be prevented by type-specific anti-HPV vaccines.
This study determined the prevalence of HPV types in non-cervical HIN and IC
diagnosed from 1999 to 2011 at a general hospital in San Luis Potosi, Mexico.
METHODS: Review of the 67 formaldehyde-fixed paraffin-embedded non-cervical
specimens initially diagnosed as HIN (n = 28) or IC (n = 39) confirmed the
presence of tumor tissue in 63 of them and changed the diagnosis of 24 from HIN
to low-grade intraepithelial neoplasias, that were excluded from the study. HPV
DNA was detected with the SPF10-DNA enzyme immunoassay in the 39 cases included,
and viral types in the HPV-positive tumors were identified with the INNO-LiPA
linear probe array. RESULTS: Among the cases included, four HIN were located in
the vagina (n = 3) and vulva (n = 1), and 35 IC in the oral cavity (n = 19),
penis (n = 8), vagina (n = 7) and vulva (n = 1). There were 13 HPV-positive cases
from the vagina (n = 7), vulva (n = 1), penis (n = 1) and oral cavity (n = 1).
The viral types identified were the high-risk types HPV16 in the vagina (n = 3)
and vulva (n = 3), HPV45 in the vagina (n = 2), HPV59 in the vagina (n = 1) and
penis (n = 1), HPV33 in the vagina (n = 1),and HPV35 in the tongue(n = 1); and
the low-risk types HPV54 in the vagina (n = 1), and HPV11 in the vulva (n = 1).
CONCLUSIONS: Five high-risk viral types (HPV16, 45, 59, 33 and 35) and two low
risk types (HPV11 and 54) infect one third of the non-cervical HIN and IC
included. Most infections are by a single HPV high-risk type, the most prevalent
one being HPV16. Vagina is the most frequent location of the HPV-positive tumors.
Vaccination against HPV16 and HPV18 could have prevented around half of the HPV
positive tumors.
PMID- 26417387
TI - The DSM-5 diagnosis of nonsuicidal self-injury disorder: a review of the
empirical literature.
AB - With the presentation of nonsuicidal self-injury disorder (NSSID) criteria in the
fifth version of the Statistical and Diagnostic Manual of Mental Disorders (DSM
5), empirical studies have emerged where the criteria have been operationalized
on samples of children, adolescents and young adults. Since NSSID is a condition
in need of further study, empirical data are crucial at this stage in order to
gather information on the suggested criteria concerning prevalence rates,
characteristics, clinical correlates and potential independence of the disorder.
A review was conducted based on published peer-reviewed empirical studies of the
DSM-5 NSSID criteria up to May 16, 2015. When the DSM-5 criteria were
operationalized on both clinical and community samples, a sample of individuals
was identified that had more general psychopathology and impairment than clinical
controls as well as those with NSSI not meeting criteria for NSSID. Across all
studies interpersonal difficulties or negative state preceding NSSI was highly
endorsed by participants, while the distress or impairment criterion tended to
have a lower endorsement. Results showed preliminary support for a distinct and
independent NSSID diagnosis, but additional empirical data are needed with direct
and structured assessment of the final DSM-5 criteria in order to reliably assess
and validate a potential diagnosis of NSSID.
PMID- 26417388
TI - The association of self-injurious behaviour and suicide attempts with recurrent
idiopathic pain in adolescents: evidence from a population-based study.
AB - BACKGROUND: While several population-based studies report that pain is
independently associated with higher rates of self-destructive behaviour
(suicidal ideation, suicide attempts, and self-injurious behaviour) in adults,
studies in adolescents are rare and limited to specific chronic pain conditions.
The aim of this study was to investigate the link between self-reported
idiopathic pain and the prevalence and frequency of self-injury (SI) and suicide
attempts in adolescents. METHODS: Data from a cross-sectional, school-based
sample was derived to assess SI, suicide attempts, recurrent pain symptoms and
various areas of emotional and behavioural problems via a self-report booklet
including the Youth Self-Report (YSR). Adolescents were assigned to two groups
(presence of pain vs. no pain) for analysis. Data from 5,504 students of 116
schools in a region of South Western Germany was available. A series of
unadjusted and adjusted multinomial logistic regression models were performed to
address the association of pain, SI, and suicide attempts. RESULTS: 929 (16.88%)
respondents reported recurrent pain in one of three areas of pain symptoms
assessed (general pain, headache, and abdominal pain). Adolescents who reported
pain also reported greater psychopathological distress on all sub-scales of the
YSR. The presence of pain was significantly associated with an increased risk
ratio (RR) for SI (1-3 incidences in the past year: RR: 2.96; >3 incidences: RR:
6.04) and suicide attempts (one attempt: RR: 3.63; multiple attempts: RR: 5.4) in
unadjusted analysis. Similarly, increased RR was observed when adjusting for
sociodemographic variables. While controlling for psychopathology attenuated this
association, it remained significant (RRs: 1.4-1.8). Sub-sequent sensitivity
analysis revealed different RR by location and frequency of pain symptoms.
CONCLUSIONS: Adolescents with recurrent idiopathic pain are more likely to report
previous incidents of SI and suicide attempts. This association is likely
mediated by the presence of psychopathological distress as consequence of
recurrent idiopathic pain. However, the observed variance in dependent variables
is only partially explained by emotional and behavioural problems. Clinicians
should be aware of these associations and interview adolescents with recurrent
symptoms of pain for the presence of self-harm, past suicide attempts and current
suicidal thoughts. Future studies addressing the neurobiology underpinnings of an
increased likelihood for self-injurious behaviour and suicide attempts in
adolescents with recurrent idiopathic pain are necessary.
PMID- 26417389
TI - Immigration as risk factor for non-suicidal self-injury and suicide attempts in
adolescents in Germany.
AB - BACKGROUND: Whereas non-suicidal self-injury (NSSI) and suicide attempts (SA) are
rather common among adolescents, the description of risk factors has often failed
to take migration into perspective. Our study aimed to describe immigration
status in adolescents with regards to their lifetime history of NSSI and SA.
METHODS: We carried out a population based study in a school community of ninth
graders (N = 452, mean age 14.85, SD 0.58) in southern Germany. Data were
collected via adolescent self report on sociodemographic variables and on NSSI
and SA using the Self Harm Behavior Questionnaire. RESULTS: Adolescents born
outside Germany showed an elevated rate of a lifetime history of NSSI and SA.
When compared to German adolescents without a (family) history of migration (NSSI
19.16%, SA 3.24%), adolescents who were born in another country had an elevated
risk for NSSI (42.86%, OR 3.36) and SA (17.86%, OR 6.78), which was higher than
the risk of adolescents who had at least one parent who had emigrated from
another country (NSSI 30.08%, OR 2.46 and SA 8.94%, OR 4.45). CONCLUSION: Our
findings should inform intervention services and prevention programs for NSSI and
suicidality in youth. Adopting such programs to include culturally sensible
modules could improve the outcome in ethnically diverse adolescents.
PMID- 26417390
TI - A cross-sectional matched sample study of nonsuicidal self-injury among young
adults: support for interpersonal and intrapersonal factors, with implications
for coping strategies.
AB - BACKGROUND: Young adults are a high-risk group for nonsuicidal self-injury
(NSSI). It is important to have a better understanding of these behaviors in
order to facilitate effective research, intervention, and treatment. Models have
been presented to explain these behaviors where emotion regulation, coping, and
support play a role. Yet conflicting results have occurred based on demographic
factors such as race and sex. While controlling for the observable demographic
factors, this study sought to examine differences between individuals who
currently engage in NSSI, engaged in NSSI in the past, and never engaged in NSSI
related to emotions, coping strategies, interpersonal support, and ethnic
identity and belonging. METHODS: Participants were selected from freshman
students at two universities, in geographically different locations in the United
States (N = 282). Participants in this study were matched on demographic factors:
race, sex, and university. This led to demographically matched groups (current,
past, never engagement in NSSI; n = 94 per group). Groups were compared on
intrapersonal factors (i.e., emotions: depression and anxiety; coping strategies:
adaptive and maladaptive; interpersonal support: family, friend, and significant
other; and ethnic identity and belonging). Descriptive statistics and ANOVA with
post hoc Scheffe were utilized to explicate differences between groups. RESULTS:
Individuals who never engaged in NSSI reported significantly higher levels of
ethnic belonging and interpersonal support and lower levels of depression and
anxiety than both groups who engaged in NSSI. Individuals who never self-injured
used less adaptive and maladaptive coping strategies than participants who self
injured. Young adults who currently engaged in NSSI reported higher levels of
depression and anxiety, higher levels of both types of coping, and perceived less
support. CONCLUSIONS: It is important to understand the differences between
individuals who self-injure in comparison to those who do not so that mental
health clinicians can provide more effective services and preventative efforts.
PMID- 26417391
TI - Research with adolescents who engage in non-suicidal self-injury: ethical
considerations and challenges.
AB - Non-suicidal self-injury (NSSI) has emerged as a significant psychiatric issue
among youth. In addition to its high prevalence rates, NSSI is associated with a
number of psychiatric issues and confers risk for varying degrees of physical
injury. It is also a risk factor for attempted suicide. Thus, youth who engage in
NSSI represent a vulnerable and high-risk population and researchers are likely
to encounter a variety of ethical challenges when conducting NSSI research.
Accordingly, it is critical that researchers be familiar with the major ethical
issues involved in NSSI research and how to effectively account for and address
them. This is important both prior to obtaining clearance from their
Institutional Review Boards and when carrying out their research. To date, there
is no consolidated resource to delineate the ethical challenges inherent to NSSI
research and how these can be effectively navigated throughout the research
process. The goals of this paper are to review international best practices in
NSSI research across the various contexts within which it is studied, to offer
guidelines for managing these issues, to identify areas in which variation in
approaches prohibits decisive recommendations, and to generate questions in need
of further consideration among scholars in this field.
PMID- 26417392
TI - Nonsuicidal self-injury: a rapidly evolving global field.
PMID- 26417393
TI - ExSTraCS 2.0: Description and Evaluation of a Scalable Learning Classifier
System.
AB - Algorithmic scalability is a major concern for any machine learning strategy in
this age of 'big data'. A large number of potentially predictive attributes is
emblematic of problems in bioinformatics, genetic epidemiology, and many other
fields. Previously, ExS-TraCS was introduced as an extended Michigan-style
supervised learning classifier system that combined a set of powerful heuristics
to successfully tackle the challenges of classification, prediction, and
knowledge discovery in complex, noisy, and heterogeneous problem domains. While
Michigan-style learning classifier systems are powerful and flexible learners,
they are not considered to be particularly scalable. For the first time, this
paper presents a complete description of the ExS-TraCS algorithm and introduces
an effective strategy to dramatically improve learning classifier system
scalability. ExSTraCS 2.0 addresses scalability with (1) a rule specificity
limit, (2) new approaches to expert knowledge guided covering and mutation
mechanisms, and (3) the implementation and utilization of the TuRF algorithm for
improving the quality of expert knowledge discovery in larger datasets.
Performance over a complex spectrum of simulated genetic datasets demonstrated
that these new mechanisms dramatically improve nearly every performance metric on
datasets with 20 attributes and made it possible for ExSTraCS to reliably scale
up to perform on related 200 and 2000-attribute datasets. ExSTraCS 2.0 was also
able to reliably solve the 6, 11, 20, 37, 70, and 135 multiplexer problems, and
did so in similar or fewer learning iterations than previously reported, with
smaller finite training sets, and without using building blocks discovered from
simpler multiplexer problems. Furthermore, ExS-TraCS usability was made simpler
through the elimination of previously critical run parameters.
PMID- 26417394
TI - Effect of ionizing radiation on the physical biology of head and neck squamous
cell carcinoma cells.
AB - Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of
cancer worldwide. Although there are numerous treatment options for HNSCC, such
as surgery, cytotoxic chemotherapy, molecularly targeted systemic therapeutics,
and radiotherapy, overall survival has not significantly improved in the last 50
years. This suggests a need for a better understanding of how these cancer cells
respond to current treatments in order to improve treatment paradigms. Ionizing
radiation (IR) promotes cancer cell death through the creation of cytotoxic DNA
lesions, including single strand breaks, base damage, crosslinks, and double
strand breaks (DSBs). As unrepaired DSBs are the most cytotoxic DNA lesion,
defining the downstream cellular responses to DSBs are critical for understanding
the mechanisms of tumor cell responses to IR. The effects of experimental IR on
HNSCC cells beyond DNA damage in vitro are ill-defined. Here we combined label
free, quantitative phase and fluorescent microscopy to define the effects of IR
on the dry mass and volume of the HNSCC cell line, UM-SCC-22A. We quantified
nuclear and cytoplasmic subcellular density alterations resulting from 8 Gy X-ray
IR and correlated these signatures with DNA and gamma-H2AX expression patterns.
This study utilizes a synergistic imaging approach to study both biophysical and
biochemical alterations in cells following radiation damage and will aid in
future understanding of cellular responses to radiation therapy.
PMID- 26417395
TI - Studying Process and Proximal Outcomes of Supervision for Motivational
Interviewing.
PMID- 26417396
TI - Management and Reconstruction in the Breast Cancer Patient With a Fungating T4b
Tumor.
AB - BACKGROUND: A subset of women with locally advanced breast cancer presented with
fungating tumor mass eroding and infiltrating the surrounding breast skin (T4b
breast cancers). These patients often have chronic pain, large open wounds,
frequent infections, malodorous drainage, social isolation, and general
debilitation that present enormous therapeutic challenges. Because of the
advanced nature of the disease, palliation, while minimizing recovery time and
maximizing quality of life, is essential. METHODS: From 2009 to 2014, a total of
12 consecutive patients underwent resection of fungating T4b breast tumors and
subsequent chest wall reconstruction. Demographic, socioeconomic, and clinical
data were collected retrospectively. RESULTS: Fifty percent of women had distant
metastases at the time of reconstruction, and 17% of women presented to the
emergency department in a hemodynamically unstable condition in either
hemorrhagic shock or septic shock, necessitating delay of reconstruction for up
to 1 week. Mean wound size for reconstruction was 473 cm(2). Reconstructive
procedures included split-thickness skin grafting and thoracoepigastric
advancement, latissimus dorsi, trapezius, and extended transverse and vertical
rectus abdominis flaps. Postoperative survival ranged from 98 to 172 days (mean =
127 days), with 9 patients currently living. Seventy-five percent of patients had
improved pain and reduced wound care needs after reconstruction. Postoperative
reconstruction-specific complications occurred in 33% of cases, with 1 patient
requiring a second operating room visit. CONCLUSIONS: Women with fungating T4b
breast cancer tumors often present with metastatic disease and have significant
need for pain and wound palliation. The reconstructive techniques performed are
reliable, efficacious in palliating pain, and reducing wound care needs and have
low complication rates.
PMID- 26417397
TI - Establishing the relationship of inhaler satisfaction, treatment adherence, and
patient outcomes: a prospective, real-world, cross-sectional survey of US adult
asthma patients and physicians.
AB - BACKGROUND: Inhaled asthma medications are the mainstay of treatment for chronic
asthma. However, nonadherence rates for long-term inhaler therapy among adults
are estimated to exceed 50 %. Nonadherence is associated with unfavorable
clinical outcomes and diminished quality of life. Research suggests that
adherence is associated with patients' satisfaction with their treatment regimen
and other factors, such as concomitant allergic rhinitis and tobacco use.
METHODS: This prospective, cross-sectional survey of physicians and their
patients evaluated the relationship between patient satisfaction with attributes
of inhaler devices, treatment adherence, and clinical outcomes. Primary care and
specialist physicians completed a physician-reported patient record form for
patients with a confirmed asthma diagnosis. Patients for whom a physician
reported form was completed were invited to complete a patient-reported form.
Both surveys collected information about demographics, symptoms, exacerbation
history, treatment, smoking status, comorbidities, type of inhaler device, and
treatment adherence. Patients also indicated the degree to which they were
satisfied with attributes of their currently prescribed inhaler device(s).
Partial least squares path modeling quantified relationships between latent
variables and clinical outcomes. RESULTS: A total of 243 patients were included
in our analysis and 41 % had poorly controlled asthma. More favorable clinical
outcomes were significantly associated with greater patient satisfaction with
drug delivery (P = 0.002), higher medication adherence (P = 0.049), no history of
tobacco use (P < 0.001), and absence of comorbid allergic rhinitis (P = 0.005).
Attributes associated with device satisfaction included patient perceptions of
consistency in the amount of drug delivery to the lungs, ease of use, and
feedback about the number of remaining doses. CONCLUSIONS: Higher patient
satisfaction with their asthma drug delivery inhaler device is a significant
predictor of more favorable clinical outcomes while allergic rhinitis and smoking
history were negatively associated with optimal control of asthma. These findings
provide clinicians with opportunities to improve patients' clinical outcomes by
tailoring choice of inhaler device therapy and providing education about the
correct way to use the device to ensure optimal outcomes. Patients will likely
benefit from medical therapy to manage comorbid allergic rhinitis and smoking
cessation interventions. Patients unable to stop smoking may require alternative
medical therapies to improve their clinical outcomes.
PMID- 26417398
TI - Allergen immunotherapy on the way to product-based evaluation-a WAO statement.
AB - Allergen immunotherapy (AIT) is widely used in clinical practice for patients
with moderate to severe allergic rhinitis due to inhalant allergens and may be
delivered via subcutaneous (SCIT) and sublingual routes (SLIT). However, the
quality of evidence for individual AIT products is very heterogeneous, and
extensions of overall conclusions ("class effects") on the efficacy and disease
modifying effects to all AIT products are unjustified. In contrast, each product
needs to be evaluated individually, based on available study results, to justify
efficacy and specific claims on sustained and disease modifying effects per
allergen and targeted patient group (children vs. adults, allergic rhinitis vs.
asthma). WAO intends to support the current development to evidence-based AIT,
which ultimately will lead to a more efficacious treatment of allergic patients
and the appropriate recognition of AIT.
PMID- 26417399
TI - Evaluation of genetic risk scores for prediction of dichotomous outcomes.
AB - Substantial uncertainty exists as to whether combining multiple disease
associated single nucleotide polymorphisms (SNPs) into a genotype risk score
(GRS) can improve the ability to predict the risk of disease in a clinically
relevant way. We calculated the ability of a simple count GRS to predict the risk
of a dichotomous outcome under both multiplicative and additive models of
combined effects. We then compared the results of these simulations with the
observed results of published GRS measured within multiple epidemiologic cohorts.
If the combined effect of each disease-associated SNP included in a GRS is
multiplicative on the risk scale, then a count GRS score should be useful for
risk prediction with as few as 10-20 SNPs. Adding additional SNPs to the GRS
under this model dramatically improves risk prediction. By contrast, if the
combined effect of each SNP included in a GRS is linearly additive on the risk
scale, a simple count GRS is unlikely to provide clinically useful risk
prediction. Adding additional SNPs to the GRS under this model does not improve
risk prediction. The combined effect of SNPs included in several published GRS
measured in several well-phenotyped epidemiologic cohort studies appears to be
more consistent with a linearly additive effect. A simple count GRS is unlikely
to be clinically useful for predicting the risk of a dichotomous outcome.
Alternative methods for constructing GRS that attempt to identify and include
SNPs that demonstrate multiplicative gene-gene or gene-environment interactive
effects are needed.
PMID- 26417400
TI - Genetic determinants of uterine fibroid size in the multiethnic NIEHS uterine
fibroid study.
AB - We conducted a follow-up association study across extended candidate chromosomal
regions for uterine leiomyoma (UL), or fibroids, to search for loci influencing
the size of UL in 916 premenopausal North American women participants to the
NIEHS uterine fibroid study. Proportional odds models with adjustments for
confounders were fitted to evaluate the association of a final set of 2,484
single nucleotide polymorphisms (SNPs) with the size of uterine fibroids measured
by transabdominal and transvaginal ultrasounds. SNP association with UL size was
tested in a case-only design comparing three categories of tumor size (small,
medium and large tumors) and in a design that included UL-free controls as the
lowest category of a four-level ordinal outcome to account for misclassifications
due to small, undetected tumors. In the case-only design, rs2285789 in SORCS2
(sortilin-related VPS10 domain containing receptor 2) was the sole variant that
remained significant after correction for multiple testing (Bonferroni-adjusted
P=0.037). Several other SNPs, namely those located in MYT1L, TMCC1 and BRCA1,
reached promising associations. In the design that included the controls, several
genes of potential relevance to UL pathogenesis were associated (Bonferroni
unadjusted P < 0.01) with tumor size, particularly LIFR-AS1 (leukemia inhibitory
factor receptor alpha-antisense RNA 1), which showed the strongest association
(Bonferroni-unadjusted P=0.0006) among the genes with regulated expression in UL.
In conclusion, SORCS2, a known GWAS candidate for circulating IGF-I and IGFBP-3,
may act through IGF-I signaling to affect the size of fibroids. Through down
regulation of LIFR, LIFR-AS1 may mediate the inhibitory action of LIF (leukemia
inhibitory factor), a cytokine involved in embryonic uterine development.
Replication analyses are needed to substantiate our reported associations of
SORCS2 and LIFR-AS1 with the size of fibroids.
PMID- 26417401
TI - The SIRT1 promoter polymorphic site rs12778366 increases IL-6 related human
mortality in the prospective study "Treviso Longeva (TRELONG)".
AB - Studies on sirtuins (SIRT), a family of proteins with deacetylase activity, have
provided convergent evidence of the key role of these enzymes in aging-linked
physiological functions. The link between SIRT1 and longevity has emerged in
model organism but few data are available in humans, in particular relying on
longitudinal studies. Here, we assessed whether a genetic variant within SIRT1
gene promoter (rs12778366) was associated to human longevity. We analyzed 586
genomic DNA (gDNA) collected in the study "Treviso Longeva" (TRELONG), including
elderly over 70 years of age from the municipality of Treviso, a town in the
Northeast of Italy, with a 11-year follow-up. We genotyped SIRT1 rs12778366 by
real-time polymerase chain reaction (RT-PCR) allelic discrimination assay. A
cross-sectional analysis performed by comparing people over and under 85 years of
age did not evidence association between rs12778366 and longevity. When we
performed a longitudinal analysis considering mortality as dependent variable, we
did not observe an association of rs12778366 with longevity in the whole
population (corrected P-value = 0.33). However, when we stratified the TRELONG
subjects according to circulating level of interleukin-6 (IL-6), a predictor of
disability and mortality, we found that rs12778366 (TC+CC) carriers were at
increased risk of mortality in comparison to the TT reference group (corrected P
value = 0.03, HR 1.47). Our data do not support a major role of rs12778366 in
human longevity, but the stratified analysis on IL-6 suggests that this variant
may be involved in the detrimental effect of high circulating IL-6 in the
elderly.
PMID- 26417402
TI - Evaluations of life style factors and the severity of Gastroesophageal reflux
disease; a case-control study.
AB - The incidence of Gastroesophageal reflux disease (GERD) has increased remarkably
worldwide. This study focuses on the background features of these patients and
evaluates the two GERD sub types; none erosive (NERD) and erosive (ERD). In a
case-control study, patients with reflux symptoms who had obtained a total score
of 8-18 of the GERD questionnaire were included. Control group consisted of their
families with lower scores and no reflux presentations. All demographic features
were recorded. Then upper GI endoscopy performed and the cases divided into two
sub groups: NERD and ERD. In the next step, all demographic data analyzed for
these two subgroups. The data were analyzed using the SPSS software version 21. A
number of 210 subjects included in each group (210 patients with GERD and 210
control group) with normal statistical distribution of age and gender. There was
a significant relationship between GERD and BMI (P=0.001), eating fatty foods
(P=0.0001), lying after meal (P=0.0001), drinking beverages with meal (0.0001),
eating spicy food (0.006) and NSAIDs use (P=0.0001). Then the cases divided into
two subgroups; NERD (n=146) and ERD (n=64). There were a significant relationship
with eating salty-smoky food (P=0.005) and eating spicy food (P=0.011). The
difference of BMI between NERD and ERD was remarkable but was not statistically
significant. Our results showed that obesity is an important risk factor for
GERD. Other possible risk factors such as NSAIDs use and certain foods and wrong
habits like lying after meal should be addressed in future longitudinal surveys.
PMID- 26417403
TI - Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer
risk in Caucasians and African Americans.
AB - Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA)
and its sulfate (DHEAS) are associated with increased breast cancer risk in
prospective studies. Genetic variants in hypothalamic-pituitary-adrenal (HPA)
axis genes may contribute to these circulating hormone levels, and consequently
to breast cancer risk. No previous studies have examined the effects of genetic
variants in HPA axis genes on breast cancer risk. We evaluated the associations
of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1,
NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women's
Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442
controls), as well as African Americans (149 cases and 246 controls). Of the 49
SNPs evaluated, one showed a nominal significant association (P for trend < 0.05)
with breast cancer risk among Caucasians, and another two among African
Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval
(95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast
cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs
(95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk
of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48
(1.20-5.13), respectively. However, these SNPs did not show significant
associations after correction for multiple testing. Our findings do not provide
strong supportive evidence for the contribution of genetic variants in these HPA
axis genes to the risk of developing breast cancer in either Caucasians or
African Americans.
PMID- 26417404
TI - Brief communication genotyping of Burkholderia pseudomallei revealed high genetic
variability among isolates from a single population group.
AB - Burkholderia pseudomallei is a soil dwelling Gram-negative bacteria predominates
in Southeast Asia zone and the tropical part of Australia. Genetic diversity has
been explored among various populations and environments worldwide. To date,
little data is available on MLST profiling of clinical B. pseudomallei isolates
in peninsular Malaysia. In this brief report, thirteen culture positive B.
pseudomallei cases collected from a single population of Terengganu state in the
Western Peninsular Malaysia and were confirmed by In-house TTS1-PCR. Isolates
were subjected for multi-locus sequence typing (MLST) to explore their genotypic
diversity and to investigate for possible clonal clustering of a certain sequence
type. Patient's clinical information was examined to investigate for clinical
correlation among the different genotypes. In spite of small sample set, MLST
results indicated predictive results; considerable genotypic diversity,
predominance and novelty among B. pseudomallei collected over a single
geographically-located population in Malaysia. Massive genotypic heterogeneity
was observed; 8 different sequence types with predominance of sequence type 54
and discovery of two novel sequence types. However, no clear pathogenomic or
organ tropism clonal relationships were predicted.
PMID- 26417405
TI - Targeting inflammation in type 2 diabetes by antibody-mediated Tyro-3, Axl, Mer
receptor activation.
PMID- 26417406
TI - Incretin physiology and pathophysiology from an Asian perspective.
AB - Incretin hormones, such as glucose-dependent insulinotropic polypeptide and
glucagon-like peptide-1, are secreted on oral nutrient ingestion and regulate
postprandial glucose homeostasis by conveying the signal of intestinal glucose
flux. In East Asians, the secretion of glucose-dependent insulinotropic
polypeptide and glucagon-like peptide-1 is not reduced in type 2 diabetes
relative to normal glucose tolerance. Although the incretin effect is blunted in
European patients with type 2 diabetes, a few East Asian studies showed no
difference in the incretin effect between type 2 diabetes and normal glucose
tolerance. Interestingly, the glucose-lowering efficacy of dipeptidyl peptidase-4
inhibitors or glucagon-like peptide-1 receptor agonists was reported to be
greater in Asians than in non-Asians. The difference in the treatment responses
could be ascribed to a different pathophysiology of type 2 diabetes (lower
insulin secretory function and less insulin resistance), lower body mass index,
different genetic makeups, preserved incretin effect and different food
compositions in East Asians compared with other ethnic groups. Based on the
currently available data, incretin-based therapies appear to be safe and well
tolerated in East Asians. Nevertheless, continuous pharmacovigilance is required.
The characteristics of incretin biology and treatment responses to incretin-based
therapies should be considered in developing ethnicity-specific treatment
guidelines and making patient-centered decisions for patients with type 2
diabetes.
PMID- 26417407
TI - Clinical characteristics of metabolic syndrome in Korea, and its comparison with
other Asian countries.
AB - Metabolic syndrome is referred to as syndrome X or insulin resistance syndrome,
and is primarily composed of abdominal obesity, diabetes, glucose intolerance,
dyslipidemia and high blood pressure. Asians have a lower frequency of obesity
than Caucasians, but have an increasing tendency toward metabolic syndrome. Thus,
metabolic syndrome poses a major challenge for public health professionals, and
is set to become a social and economic problem in Asian populations. Most data on
metabolic syndrome are based on studies from Western countries with only limited
information derived from Asian populations. Recently, several studies were
carried out on a large scale that represents the general Korean population. The
prevalence of metabolic syndrome in Korean adults has varied depending on the
study designs and different criteria, but shows a distinct increasing trend of
metabolic syndrome driven by an increase in abdominal obesity and dyslipidemia.
Given the rapid economic progression of Korea over the past 30 years along with a
rise of the aged population, it is expected that the prevalence of metabolic
syndrome will further increase. Therefore, a proactive strategy at the
governmental level for metabolic syndrome prevention should be implemented,
reducing abdominal obesity and dyslipidemia. Healthy dietary habits and regular
exercise should be emphasized as a part of such a strategy.
PMID- 26417408
TI - Fructose induces glucose-dependent insulinotropic polypeptide, glucagon-like
peptide-1 and insulin secretion: Role of adenosine triphosphate-sensitive K(+)
channels.
AB - Adenosine triphosphate-sensitive K(+) (KATP) channels play an essential role in
glucose-induced insulin secretion from pancreatic beta-cells. It was recently
reported that the KATP channel is also found in the enteroendocrine K-cells and L
cells that secrete glucose-dependent insulinotropic polypeptide (GIP) and
glucagon-like peptide-1 (GLP-1), respectively. In the present study, we
investigated the involvement of the KATP channel in fructose-induced GIP, GLP-1
and insulin secretion in mice. Fructose stimulated GIP secretion, but
pretreatment with diazoxide, a KATP channel activator, did not affect fructose
induced GIP secretion under streptozotocin-induced hyperglycemic conditions.
Fructose significantly stimulated insulin secretion in Kir6.2 (+/+) mice, but not
in mice lacking KATP channels (Kir6.2 (-/-) ), and fructose stimulated GLP-1
secretion in both Kir6.2 (+/+) mice and Kir6.2 (-/-) mice under the normoglycemic
condition. In addition, diazoxide completely blocked fructose-induced insulin
secretion in Kir6.2 (+/+) mice and in MIN6-K8 beta-cells. These results show that
fructose-induced GIP and GLP-1 secretion is KATP channel-independent and that
fructose-induced insulin secretion is KATP channel-dependent.
PMID- 26417409
TI - Regardless of central obesity, metabolic syndrome is a significant predictor of
type 2 diabetes in Japanese Americans.
AB - AIMS/INTRODUCTION: The impact of metabolic syndrome (MetS) on the development of
type 2 diabetes has been reported in different ethnic populations. However,
whether central obesity is an essential component as a diagnostic criterion for
MetS remains a controversial topic. The aim of the present study was to
investigate the association between MetS and the incidence of type 2 diabetes
with or without central obesity in a Japanese American population. MATERIALS AND
METHODS: We examined whether MetS predicts incident type 2 diabetes among 928
Japanese American participants who did not have diabetes enrolled in an ongoing
medical survey between 1992 and 2007. MetS was defined on the basis of American
Heart Association/National Heart, Lung, and Blood Institute criteria. The average
follow-up period was approximately 6.8 years. RESULTS: During the follow-up
period, 116 new cases of diabetes were diagnosed. Compared to the participants
without MetS, the hazard ratio (HR) for incident type 2 diabetes was
significantly higher in participants with MetS, after adjustment for sex, age and
impaired glucose tolerance (HR 1.64, 95% CI 1.11-2.42). The risk of type 2
diabetes was found to be significantly higher in participants with MetS but
without central obesity (HR 2.07, 95% CI 1.25-3.41), as well as in participants
with MetS and with central obesity (HR 2.46, 95% CI 1.51-4.01) than in
participants with neither MetS nor central obesity, after adjustment for sex, age
and impaired glucose tolerance. CONCLUSIONS: These results show that the presence
of MetS, with or without central obesity, could independently predict the
development of type 2 diabetes in Japanese Americans.
PMID- 26417410
TI - Impact of population aging on trends in diabetes prevalence: A meta-regression
analysis of 160,000 Japanese adults.
AB - AIMS/INTRODUCTION: To provide age- and sex-specific trends, age-standardized
trends, and projections of diabetes prevalence through the year 2030 in the
Japanese adult population. MATERIALS AND METHODS: In the present meta-regression
analysis, we included 161,087 adults from six studies and nine national health
surveys carried out between 1988 and 2011 in Japan. We assessed the prevalence of
diabetes using a recorded history of diabetes or, for the population of
individuals without known diabetes, either a glycated hemoglobin level of >=6.5%
(48 mmol/mol) or the 1999 World Health Organization criteria (i.e., a fasting
plasma glucose level of >=126 mg/dL and/or 2-h glucose level of >=200 mg/dL in
the 75-g oral glucose tolerance test). RESULTS: For both sexes, prevalence
appeared to remain unchanged over the years in all age categories except for men
aged 70 years or older, in whom a significant increase in prevalence with time
was observed. Age-standardized diabetes prevalence estimates based on the
Japanese population of the corresponding year showed marked increasing trends:
diabetes prevalence was 6.1% among women (95% confidence interval [CI] 5.5-6.7),
9.9% (95% CI 9.2-10.6) among men, and 7.9% (95% CI 7.5-8.4) among the total
population in 2010, and was expected to rise by 2030 to 6.7% (95% CI 5.2-9.2),
13.1% (95% CI 10.9-16.7) and 9.8% (95% CI 8.5-12.0), respectively. In contrast,
the age-standardized diabetes prevalence using a fixed population appeared to
remain unchanged. CONCLUSIONS: This large-scale meta-regression analysis shows
that a substantial increase in diabetes prevalence is expected in Japan during
the next few decades, mainly as a result of the aging of the adult population.
PMID- 26417411
TI - Establishment of maturity-onset diabetes of the young-induced pluripotent stem
cells from a Japanese patient.
AB - Maturity-onset diabetes of the young (MODY) is a heterozygous monogenic diabetes;
more than 13 disease genes have been identified. However, the pathogenesis of
MODY is not fully understood, because the pancreatic beta-cells of the patients
are inaccessable. Therefore, we attempted to establish MODY patient-derived
induced pluripotent stem cells (MODY-iPS) cells to investigate the pathogenic
mechanism of MODY by inducing pancreatic beta-cells. We established MODY5-iPS
cells from a Japanese patient with MODY5 (R177X), and confirmed that MODY5-iPS
cells possessed the characteristics of pluripotent stem cells. In the course of
differentiation from MODY5-iPS cells into pancreatic beta-cells, we examined the
disease gene, HNF1B messenger ribonucleic acid. We found that the amount of R177X
mutant transcripts was much less than that of wild ones, but they increased after
adding cycloheximide to the medium. These results suggest that these R177X mutant
messenger ribonucleic acids are disrupted by nonsense-mediated messenger
ribonucleic acid decay in MODY-iPS cells during the developmental stages of
pancreatic beta-cells.
PMID- 26417413
TI - Extent of weight reduction necessary for minimization of diabetes risk in
Japanese men with visceral fat accumulation and glycated hemoglobin of 5.6-6.4.
AB - AIMS/INTRODUCTION: Weight reduction improves glycemic control in obese men with
glycated hemoglobin (HbA1c) of 5.6-6.4%, suggesting that it can prevent the
development of diabetes in these patients. The aim of the present study was to
quantify the amount of weight reduction necessary for minimization of diabetes
risk in Japanese men with visceral fat accumulation. MATERIALS AND METHODS: The
study participants were 482 men with an estimated visceral fat area of >=100
cm(2), HbA1c of 5.6-6.4%, fasting plasma glucose (FPG) of <126 mg/dL or casual
plasma glucose <200 mg/dL. They were divided into two groups based on weight
change at the end of the 3-year follow-up period (weight gain and weight loss
groups). The weight loss group was classified into quartile subgroups (lowest
group, 0 to <1.2%: second lowest group, >=1.2 to <2.5%: second highest group,
>=2.5 to <4.3%: highest group, >=4.3% weight loss). The development of diabetes
at the end-point represented a rise in HbA1c to >=6.5% or FPG >=126 mg/dL, or
casual plasma glucose >=200 mg/dL. RESULTS: The cumulative incidence of diabetes
at the end of the 3-year follow-up period was 16.2% in the weight gain group and
10.1% in the weight loss group (P not significant). The incidence of diabetes was
significantly lower in the highest weight loss group (3.1%), but not in the
second highest, the second lowest and the lowest weight loss groups (9.7, 10.1
and 18.3%), compared with the weight gain group. CONCLUSIONS: Minimization of the
risk of diabetes in Japanese men with visceral fat accumulation requires a
minimum of 4-5% weight loss in those with HbA1c of 5.6-6.4%.
PMID- 26417412
TI - Correlation of serum testosterone with insulin resistance in elderly male type 2
diabetes mellitus patients with osteoporosis.
AB - AIMS/INTRODUCTION: The present study was designed to investigate the correlations
between the serum testosterone level and insulin sensitivity in elderly male type
2 diabetes patients with osteoporosis. MATERIALS AND METHODS: A total of 35
elderly male patients with type 2 diabetes (type 2 diabetes group), 30 elderly
male type 2 diabetes patients combined with osteoporosis (DO group) and 30
healthy elderly men (normal control group) participated in the present study. The
fasting plasma glucose, fasting insulin, testosterone (T) and estradiol (E2) were
measured. The insulin sensitivity index (ISI), homeostasis model assessment of
insulin resistance (HOMA-IR) and E2/T were calculated. Then, the correlations of
serum testosterone level with ISI and HOMA-IR were analyzed by statistical
methods. RESULTS: The HOMA-IR, E2 and E2/T of the type 2 diabetes group and DO
group were significantly increased, whereas the bone mineral density, ISI, T and
sex hormone binding globulin were decreased compared with those of the normal
control group. Serum testosterone levels of the type 2 diabetes group and DO
group were negatively correlated to the HOMA-IR (r = -0.496, -0.506; P < 0.05),
whereas they were positively correlated to the fasting insulin (r = 0.281, 0.292;
P < 0.05) and ISI (r = 0.364, 0.403; P < 0.05). CONCLUSIONS: The reduced level of
serum testosterone in elderly male type 2 diabetes patients with osteoporosis
might promote insulin resistance.
PMID- 26417414
TI - Comparison of sitagliptin with nateglinide on postprandial glucose and related
hormones in drug-naive Japanese patients with type 2 diabetes mellitus: A pilot
study.
AB - AIMS/INTRODUCTION: Dipeptidyl peptidase-4 inhibitors and glinides are effective
in reducing postprandial hyperglycemia. However, little information is available
on the comparative effects of the two drugs on the levels of postprandial
glucose. The aim of the present study was to compare the effects of sitagliptin
and nateglinide on meal tolerance tests in drug-naive patients with type 2
diabetes mellitus. MATERIALS AND METHODS: The study participants were 19 patients
with type 2 diabetes mellitus, which was inadequately controlled by diet and
exercise. An open-label, prospective, cross-over trial was carried out to compare
the effects of single-dose sitagliptin and nateglinide on the postprandial
glucose level and its related hormones during meal tests. RESULTS: The change in
area under the curve (AUC) of glucose from 0 to 180 min (AUC0-180 min) during the
meal test by nateglinide was similar to that by sitagliptin. As expected, the
change in active glucagon like peptide-1 was significantly higher after a single
dose of sitagliptin than nateglinide. Then, insulin secretion relative to glucose
elevation (ISG) (DeltaISG0-180 min: DeltaAUC0-180 min insulin/AUC0-180 min
glucose) was significantly enhanced by nateglinide compared with sitagliptin.
Conversely, glucagon level (DeltaAUC0-180 min glucagon) was increased by
administration of nateglinide, whereas the glucagon level was reduced by
administration of sitagliptin. CONCLUSIONS: The effects of sitagliptin on
postprandial glucose levels were similar to those of nateglinide in drug-naive
type 2 diabetes patients. However, the induced changes in insulin, active
glucagon-like peptide-1 and glucagon during meal loading suggest that reduction
of postprandial hyperglycemia was achieved by the unique effect of each drug.
PMID- 26417415
TI - Fear of hypoglycemia and its determinants in insulin-treated patients with type 2
diabetes mellitus.
AB - The aim of the present study was to investigate the prevalence of fear of
hypoglycemia, in association with severe hypoglycemia and social factors, in
insulin-treated patients with type 2 diabetes mellitus. A questionnaire survey on
hypoglycemia and patient-physician communication was carried out in 355 patients
with insulin-treated type 2 diabetes mellitus patients at 16 hospitals and
clinics. A fear of hypoglycemia was reported by 27.7% of patients. A stepwise
logistic regression analysis found that severe hypoglycemia during the past 1
year was a significant determinant of fear of hypoglycemia (odds ratio 2.16, 95%
confidence interval 1.06-4.41; P = 0.034), and age (odds ratio 1.02, 95%
confidence interval 1.00-1.05, P = 0.038) and living alone (odds ratio 1.93, 95%
confidence interval 1.00-3.73, P < 0.05) were significantly higher in patients
with fear of hypoglycemia than in those without it.
PMID- 26417416
TI - Irisin levels are associated with urotensin II levels in diabetic patients.
AB - AIMS/INTRODUCTION: Irisin is a newly identified myokine that can promote energy
expenditure. Previous studies showed that circulating urotensin II (UII) levels
were increased in diabetes, and UII could inhibit the glucose transport in
skeletal muscle in diabetic mice and aggravated insulin resistance. We presumed
that irisin levels are associated with UII in diabetic patients. MATERIALS AND
METHODS: A total of 71 patients with type 2 diabetes and 40 healthy subjects were
recruited. Blood and urinary irisin concentrations were measured by using enzyme
linked immunosorbent assay, and UII concentrations were measured by bioelectrical
impedance analysis. Every participant's body composition was analyzed by
bioelectrical impedance. RESULTS: The serum irisin levels were significantly
lower in diabetic patients than that of controls, whereas serum UII levels were
significantly higher in diabetic patients than that in that of controls. Serum
irisin levels were negatively associated with circulating UII, hemoglobin A1c and
the natural logarithm transformation of urinary albumin excretion, whereas serum
irisin was positively associated with estimated glomerular filtration rate, and
low-density lipoprotein cholesterol and urinary irisin were positively associated
with urinary UII. Furthermore, circulating irisin is positively associated with
muscle mass, whereas circulating UII is negatively associated with muscle mass in
diabetic patients. Hemoglobin A1c and circulating UII are independent
determinants of circulating irisin by multiple regression analysis. CONCLUSIONS:
The present results provide the clinical evidence of an association between
irisin and UII in diabetic patients. Hemoglobin A1c and circulating UII are
independent determinants of circulating irisin. Our results hint that UII and
high glucose might inhibit the release of irisin from skeletal muscle in diabetic
patients.
PMID- 26417417
TI - Impacts of the Great East Japan Earthquake on diabetic patients.
AB - AIMS/INTRODUCTION: We investigated impacts of the Great East Japan Earthquake on
diabetic patients and characterized those with disaster-susceptible diabetes.
MATERIALS AND METHODS: We enrolled 497 diabetic patients who had been followed at
hospitals in devastated areas. We collected metabolic parameters prospectively, 1
and 3 months after the earthquake, and retrospectively for pre-earthquake time
points. Questionnaire surveys were carried out regarding earthquake-related
damage and post-earthquake lifestyle alterations. Available data were analyzed to
examine associations with post-earthquake glycosylated hemoglobin alterations.
RESULTS: The mean glycosylated hemoglobin level of the participants was not
elevated at 1 month, and was significantly decreased at 3 months as compared with
the pre-earthquake glycosylated hemoglobin. There were no significant differences
in earthquake-related damage or lifestyle alterations between the improved and
worsened glycemic control groups according to the data obtained from the
questionnaire survey. As reported, fasting serum C-peptide levels were
significantly lower in the worsened glycemic control group (P < 0.05). Notably,
plasma noradrenaline levels were significantly higher in the worsened glycemic
control group (P < 0.05). Furthermore, at 1 month after the earthquake, the
plasma noradrenaline level was significantly higher in the low C-peptide group
(fasting serum C-peptide <1.0 ng/mL) than in the high C-peptide group (fasting
serum C-peptide >=1.0 ng/mL), but this difference had disappeared by 3 months
after the earthquake. These findings show that post-earthquake plasma
noradrenaline levels were temporarily increased in the low C-peptide group.
CONCLUSIONS: Sympathetic nerve activation might be elicited more easily in
subjects with lower endogenous insulin secretory capacity, and could be involved
in the mechanism underlying post-earthquake worsening of glycemic control.
PMID- 26417418
TI - Case of ketoacidosis by a sodium-glucose cotransporter 2 inhibitor in a diabetic
patient with a low-carbohydrate diet.
AB - We present a case of a 32-year-old diabetic woman with Prader-Willi syndrome who
developed severe ketoacidosis caused by a sodium-glucose cotransporter 2 (SGLT2)
inhibitor, a novel class of antihyperglycemic agents, during a strict low
carbohydrate diet. At admission, a serum glucose level of 191 mg/dL was
relatively low, though laboratory evaluations showed severe ketoacidosis. This is
the first report of ketoacidosis caused by a SGLT2 inhibitor. It is necessary to
not only pay attention when using a SGLT2 inhibitor in patients following a low
carbohydrate diet, but also to start a low-carbohydrate diet in patients treated
with a SGLT2 inhibitor because of a high risk for developing ketoacidosis.
PMID- 26417419
TI - Protamine-containing insulin allergy and renal dysfunction in a patient with type
2 diabetes.
AB - An 87-year-old woman with type 2 diabetes noticed a red itchy rash at the insulin
injection sites 3 weeks after initiation of premixed insulin therapy. Laboratory
data at that time showed marked eosinophilia and progression of renal
dysfunction. Insulin treatment was discontinued, and antidiabetic oral drugs were
used, as well as intravenous injection of dexamethasone. Her skin lesions
disappeared, and both eosinophilia and renal dysfunction gradually improved. The
results of skin prick tests and measurement of specific immunoglobulin E
antibodies suggested that the insulin allergy was caused by protamine. Although
cases of insulin allergy associated with renal dysfunction are rare, we must be
aware, especially for elderly patients with poor renal function in the first
application of insulin.
PMID- 26417420
TI - Homeodomain interacting protein kinase 2 is downregulated through the peroxisome
proliferator-activated receptor gamma signaling pathway in an insulin-resistant
population.
PMID- 26417421
TI - CHEMICAL SELECTIVITY OF NUCLEOBASE ADDUCTION RELATIVE TO IN VIVO MUTATION SITES
ON EXON 7 FRAGMENT OF P53 TUMOR SUPPRESSOR GENE.
AB - Damage to p53 tumor suppressor gene is found in half of all human cancers.
Databases integrating studies of large numbers of tumors and cancer cell cultures
show that mutation sites of specific p53 codons are correlated with specific
types of cancers. If the most frequently damaged p53 codons in vivo correlate
with the most frequent chemical damage sites in vitro, predictions of organ
specific cancer risks might result. Herein, we describe LC-MS/MS methodology to
reveal codons with metabolite-adducted nucleobases by LC-MS/MS for
oligonucleotides longer than 20 base pairs. Specifically, we used a known
carcinogen, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) to determine the
most frequently adducted nucleobases within codons. We used a known sequence of
32 base pairs (bp) representing part of p53 exon 7 with 5 possible reactive hot
spots. This is the first nucleobase reactivity study of a double stranded DNA p53
fragment featuring more than 20 base pairs with multiple reactive sites. We
reacted the 32 bp fragment with benzo[a]pyrene metabolite BPDE that undergoes
nucleophilic substitution by DNA bases. Liquid chromatography-mass spectrometry
(LC-MS/MS) was used for sequencing of oligonucleotide products from the reacted
32 bp fragment after fragmentation by a restriction endonuclease. Analysis of the
adducted p53 fragment compared with unreacted fragment revealed guanines of
codons 248 and 244 as most frequently targeted, which are also mutated with high
frequency in human tumors. Codon 248 is mutated in non-small cell and small cell
lung, head and neck, colorectal and skin cancer, while codon 244 is mutated in
small cell lung cancer, all of which involve possible BDPE exposure. Results
suggest the utility of this approach for screening of adducted p53 gene by drugs
and environmental chemicals to predict risks for organ specific cancers.
PMID- 26417422
TI - Efficient Chemoenzymatic Synthesis of an N-glycan Isomer Library.
AB - Quantification, characterization and biofunctional studies of N-glycans on
proteins remain challenging tasks due to complexity, diversity and low abundance
of these glycans. The availability of structurally defined N-glycans (especially
isomers) libraries is essential to help on solving these tasks. We reported
herein an efficient chemoenzymatic strategy, namely Core Synthesis/Enzymatic
Extension (CSEE), for rapid production of diverse N-glycans. Starting with 5
chemically prepared building blocks, 8 N-glycan core structures containing one or
two terminal N-acetyl-D-glucosamine (GlcNAc) residue(s) were chemically
synthesized via consistent use of oligosaccharyl thioethers as glycosylation
donors in the convergent fragment coupling strategy. Each of these core
structures was then extended to 5 to 15 N-glycan sequences by enzymatic reactions
catalyzed by 4 robust glycosyltransferases. Success in synthesizing N-glycans
with Neu5Gc and core-fucosylation further expanded the ability of enzymatic
extension. High performance liquid chromatography with an amide column enabled
rapid and efficient purification (>98% purity) of N-glycans in milligram scales.
A total of 73 N-glycans (63 isomers) were successfully prepared and characterized
by MS2 and NMR. The CSEE strategy provides a practical approach for "mass
production" of structurally defined N-glycans, which are important standards and
probes for Glycoscience.
PMID- 26417423
TI - Protonation state of the Cu4S2 CuZ site in nitrous oxide reductase: redox
dependence and insight into reactivity.
AB - Spectroscopic and computational methods have been used to determine the
protonation state of the edge sulfur ligand in the Cu4S2 CuZ form of the active
site of nitrous oxide reductase (N2OR) in its 3CuICuII (1-hole) and 2CuI2CuII (2
hole) redox states. The EPR, absorption, and MCD spectra of 1-hole CuZ indicate
that the unpaired spin in this site is evenly delocalized over CuI, CuII, and
CuIV. 1-hole CuZ is shown to have a MU2-thiolate edge ligand from the observation
of S-H bending modes in the resonance Raman spectrum at 450 and 492 cm-1 that
have significant deuterium isotope shifts (-137 cm-1) and are not perturbed up to
pH 10. 2-hole CuZ is characterized with absorption and resonance Raman
spectroscopies as having two Cu-S stretching vibrations that profile differently.
DFT models of the 1-hole and 2-hole CuZ sites are correlated to these
spectroscopic features to determine that 2-hole CuZ has a MU2-sulfide edge ligand
at neutral pH. The slow two electron (+1 proton) reduction of N2O by 1-hole CuZ
is discussed and the possibility of a reaction between 2-hole CuZ and O2 is
considered.
PMID- 26417424
TI - MM Quadruply Bonded Complexes Supported by Vinylbenzoate Ligands: Synthesis,
Characterization, Photophysical Properties and Application as Synthons.
AB - From the reactions between M2(T i PB)4 compounds and meta and para - vinylbenzoic
acids (2 equiv) in toluene at room temperature the compounds trans-M2(T i PB)2L2,
where L = m-vinylbenzoate 1A (M = Mo) and 1B (M = W) and T i PB = 2,4,6
triisopropylbenzoate, and where L = p-vinylbenzoate 2A (M = Mo) and 2B (M = W)
have been isolated. Compounds 1A and 2A have been shown to undergo Heck carbon
carbon coupling reactions with phenyliodide to produce trans-Mo2(T i PB)2(O2CC6H4
m-CH=CH-C6H5)2,3A and trans-Mo2(T i PB)2(O2CC6H4-p-CH=CH-C6H5)2, 4A. The
molybdenum compounds 1A and 2A have been structurally characterized by single
crystal X-ray crystallography. All the new compounds have been characterized by
1H NMR, IR, UV-Visible absorption and emission spectroscopy, high resolution
MALDITOF MS, fs- and ns- transient absorption spectroscopy and fs- time-resolved
IR spectroscopy. Electronic structure calculations employing density functional
theory, DFT, and time-dependent DFT have been employed to aid in the
interpretation of spectral data. All compounds show intense absorptions in the
visible region corresponding to M2delta to Lpi* charge transfer transitions. The
lifetimes of the 1MLCT state fall in the range of 1 - 10 ps and for the
molybdenum complexes the T1 states are 3deltadelta* with lifetimes ~50 MUs while
for the tungsten complexes the T1 are 3 MLCT with lifetimes in the range of 3 -
10 ns.
PMID- 26417425
TI - Graphene-DNAzyme Junctions: A Platform for Direct Metal Ion Detection with
Ultrahigh Sensitivity.
AB - Many metal ions are present in biology and in the human body in trace amounts.
Despite numerous efforts, metal sensors with ultrahigh sensitivity (< a few
picomolar) are rarely achieved. Here, we describe a platform method that
integrates a Cu2+-dependent DNAzyme into graphene-molecule junctions and its
application for direct detection of paramagnetic Cu2+ with femtomolar sensitivity
and high selectivity. Since DNAzymes specific for other metal ions can be
obtained through in vitro selection, the method demonstrated here can be applied
to the detection of a broad range of other metal ions.
PMID- 26417426
TI - Magnetic circular dichroism and computational study of mononuclear and dinuclear
iron(IV) complexes.
AB - High-valent iron(IV)-oxo species are key intermediates in the catalytic cycles of
a range of O2-activating iron enzymes. This work presents a detailed study of the
electronic structures of mononuclear ([FeIV(O)(L)(NCMe)]2+, 1, L = tris(3,5
dimethyl-4-methoxylpyridyl-2-methyl)amine) and dinuclear ([(L)FeIV(O)(MU
O)FeIV(OH)(L)]3+, 2) iron(IV) complexes using absorption (ABS), magnetic circular
dichroism (MCD) spectroscopy and wave-function-based quantum chemical
calculations. For complex 1, the experimental MCD spectra at 2-10 K are dominated
by a broad positive C-term band between 12000 and 18000 cm-1. As the temperature
increases up to ~20 K, this feature is gradually replaced by a derivative-shaped
signal. The computed MCD spectra are in excellent agreement with experiment,
which reproduce not only the excitation energies and the MCD signs of key
transitions but also their temperature-dependent intensity variations. To further
corroborate the assignments suggested by the calculations, the individual MCD
sign for each transition is independently determined from the corresponding
electron donating and accepting orbitals. Thus, unambiguous assignments can be
made for the observed transitions in 1. The ABS/MCD data of complex 2 exhibit ten
features that are assigned as ligand-field transitions or oxo- or hydroxo-to
metal charge transfer bands, based on MCD/ABS intensity ratios, calculated
excitation energies, polarizations, and MCD signs. In comparison with complex 1,
the electronic structure of the FeIV=O site is not significantly perturbed by the
binding to another iron(IV) center. This may explain the experimental finding
that complexes 1 and 2 have similar reactivities toward C-H bond activation and O
atom transfer.
PMID- 26417427
TI - Significant Improvement of Oxidase Activity through the Genetic Incorporation of
a Redox-active Unnatural Amino Acid.
AB - While nature employs various covalent and non-covalent strategies to modulate
tyrosine (Y) redox potential and pKa to optimize enzyme activities, such
approaches have not been systematically applied for the design of functional
metalloproteins. Through the genetic incorporation of 3-methoxytyrosine (OMeY)
into myoglobin, we recapitulated important features of cytochrome c oxidase (CcO)
into this small soluble protein, which exhibits selective O2 reduction activity
while generating small amount of reactive oxygen species (ROS). These results
demonstrate that the electron donating ability of a tyrosine residue in the
active site is important for CcO function. Moreover, we elucidated the structural
basis for the genetic incorporation of OMeY into proteins, by solving the X-ray
structure of OMeY specific aminoacyl-tRNA synthetase in complex with OMeY.
PMID- 26417428
TI - Unified Approach to Prenylated Indole Alkaloids: Total Syntheses of (-)-17
Hydroxy-Citrinalin B, (+)-Stephacidin A, and (+)-Notoamide I.
AB - A unified strategy for the synthesis of congeners of the prenylated indole
alkaloids is presented. This strategy has yielded the first synthesis of the
natural product (-)-17-hydroxy-citrinalin B as well as syntheses of (+)
stephacidin A and (+)-notoamide I. An enolate addition to an in situ generated
isocyanate was utilized in forging a key bicyclo[2.2.2]diazaoctane moiety, and in
this way connected the two structural classes of the prenylated indole alkaloids
through synthesis.
PMID- 26417429
TI - Evolution and development of the adelphophagic, intracapsular Schmidt's larva of
the nemertean Lineus ruber.
AB - BACKGROUND: The life cycle of many animals includes a larval stage, which has
diversified into an astonishing variety of ecological strategies. The Nemertea is
a group of spiralians that exhibits a broad diversity of larval forms, including
the iconic pilidium. A pelagic planktotrophic pilidium is the ancestral form in
the Pilidiophora, but several lineages exhibit deviations of this condition,
mostly as a transition to pelagic lecithotrophy. The most extreme case occurs,
however, in the Pilidiophoran Lineus ruber, which exhibits an adelphophagic
intracapsular pilidium, the so-called Schmidt's larva. RESULTS: We combined
confocal laser scanning microscopy and gene expression studies to characterize
the development and metamorphosis of the Schmidt's larva of L. ruber. The larva
forms after gastrulation, and comprises a thin epidermis, a proboscis rudiment
and two pairs of imaginal discs from which the juvenile will develop. The cells
internalized during gastrulation form a blind gut and the blastopore gives rise
to the mouth of the larva and juvenile. The Schmidt's larva eats other siblings
that occupy the same egg capsule, accumulating nutrients for the juvenile. A
gradual metamorphosis involves the differentiation of the juvenile cell types
from the imaginal discs and the shedding of the larval epidermis. The expression
of evolutionarily conserved anterior (foxQ2, six3/6, gsc, otx), endomesodermal
(foxA, GATA456-a, twi-a) and posterior (evx, cdx) markers demonstrate that the
juvenile retains the molecular patterning of the Schmidt's larva. After
metamorphosis, the juveniles stay over 20 days within the egg masses, until they
are fully mature and hatch. CONCLUSIONS: The evolution of the intracapsular
Schmidt's larva involved the loss of the typical feeding structures of the
planktotrophic pilidium and a precocious formation of the imaginal discs, as also
observed in other pelagic lecithotrophic forms. However, no special adaptations
are observed related to adelphophagy. As in planktotrophic pilidium, the
molecular mechanism patterning the juvenile is only active in the imaginal discs
and not during the early development of the larva, suggesting two separate
molecular programs during nemertean embryogenesis. Our results illuminate the
diversification of larval forms in the Pilidiophora and Nemertea, and thus on the
developmental mechanisms underlying metazoan larval evolution.
PMID- 26417430
TI - Skeletal muscle interleukin 15 promotes CD8(+) T-cell function and autoimmune
myositis.
AB - BACKGROUND: Interleukin 15 (IL-15) is thought to be abundant in the skeletal
muscle under steady state conditions based on RNA expression; however, the IL-15
RNA level may not reflect the protein level due to post-transcriptional
regulation. Although exogenous protein treatment and overexpression studies
indicated IL-15 functions in the skeletal muscle, how the skeletal muscle cell
uses IL-15 remains unclear. In myositis patients, IL-15 protein is up-regulated
in the skeletal muscle. Given the supporting role of IL-15 in CD8(+) T-cell
survival and activation and the pathogenic role of cytotoxic CD8(+) T cells in
polymyositis and inclusion-body myositis, we hypothesize that IL-15 produced by
the inflamed skeletal muscle promotes myositis via CD8(+) T cells. METHODS:
Expression of IL-15 and IL-15 receptors at the protein level by skeletal muscle
cells were examined under steady state and cytokine stimulation conditions. The
functions of IL-15 in the skeletal muscle were investigated using Il15 knockout
(Il15 (-/-) ) mice. The immune regulatory role of skeletal muscle IL-15 was
determined by co-culturing cytokine-stimulated muscle cells and memory-like
CD8(+) T cells in vitro and by inducing autoimmune myositis in skeletal-muscle
specific Il15 (-/-) mice. RESULTS: We found that the IL-15 protein was not
expressed by skeletal muscle cells under steady state condition but induced by
tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma)
stimulation and expressed as IL-15/IL-15 receptor alpha (IL-15Ralpha) complex.
Skeletal muscle cells expressed a scanty amount of IL-15 receptor beta (IL
15Rbeta) under either conditions and only responded to a high concentration of IL
15 hyperagonist, but not IL-15. Consistently, deficiency of endogenous IL-15
affected neither skeletal muscle growth nor its responses to TNF-alpha and IFN
gamma. On the other hand, the cytokine-stimulated skeletal muscle cells presented
antigen and provided IL-15 to promote the effector function of memory-like CD8(+)
T cells. Genetic ablation of Il15 in skeletal muscle cells greatly ameliorated
autoimmune myositis in mice. CONCLUSIONS: These findings together indicate that
skeletal muscle IL-15 directly regulates immune effector cells but not muscle
cells and thus presents a potential therapeutic target for myositis.
PMID- 26417432
TI - Understanding the biosynthesis of platelets-derived extracellular vesicles.
AB - Platelet-derived extracellular vesicles (PEVs) are described as sub-cellular
vesicles released into circulation upon platelets shear stress, activation,
injury, or apoptosis. They are considered as universal biomarkers in a wide range
of physiological and pathological processes. They are of tremendous significance
for the prediction, diagnosis, and observation of the therapeutic success of many
diseases. Understanding their biosynthesis and therefore functional properties
would contribute to a better understanding of the pathological mechanisms leading
to various diseases in which their levels are raised and they are implicated. The
review takes a critical look at the historical background of PEVs, their
structural components, the mechanism of their formation, physiological, and
exogenous stimuli inducing their release and their detection. It concludes by
highlighting on the importance of undertaking in-depth studies into PEVs
biosynthesis and subsequently gaining a better understanding of their biological
role in general.
PMID- 26417431
TI - MLBCD: a machine learning tool for big clinical data.
AB - BACKGROUND: Predictive modeling is fundamental for extracting value from large
clinical data sets, or "big clinical data," advancing clinical research, and
improving healthcare. Machine learning is a powerful approach to predictive
modeling. Two factors make machine learning challenging for healthcare
researchers. First, before training a machine learning model, the values of one
or more model parameters called hyper-parameters must typically be specified. Due
to their inexperience with machine learning, it is hard for healthcare
researchers to choose an appropriate algorithm and hyper-parameter values.
Second, many clinical data are stored in a special format. These data must be
iteratively transformed into the relational table format before conducting
predictive modeling. This transformation is time-consuming and requires computing
expertise. METHODS: This paper presents our vision for and design of MLBCD
(Machine Learning for Big Clinical Data), a new software system aiming to address
these challenges and facilitate building machine learning predictive models using
big clinical data. RESULTS: The paper describes MLBCD's design in detail.
CONCLUSIONS: By making machine learning accessible to healthcare researchers,
MLBCD will open the use of big clinical data and increase the ability to foster
biomedical discovery and improve care.
PMID- 26417433
TI - Differences in antigen-specific CD4+ responses to opportunistic infections in HIV
infection.
AB - HIV-infected individuals with severe immunodeficiency are at risk of
opportunistic infection (OI). Tuberculosis (TB) may occur without substantial
immune suppression suggesting an early and sustained adverse impact of HIV on
Mycobacterium tuberculosis (MTB)-specific cell mediated immunity (CMI). This
prospective observational cohort study aimed to observe differences in OI
specific and MTB-specific CMI that might underlie this. Using polychromatic flow
cytometry, we compared CD4+ responses to MTB, cytomegalovirus (CMV), Epstein-Barr
virus (EBV) and Candida albicans in individuals with and without HIV infection.
MTB-specific CD4+ T-cells were more polyfunctional than virus specific (CMV/EBV)
CD4+ T-cells which predominantly secreted IFN-gamma (IFN-gamma) only. There was a
reduced frequency of IFN-gamma and IL-2 (IL-2)-dual-MTB-specific cells in HIV
infected individuals, which was not apparent for the other pathogens. MTB
specific cells were less differentiated especially compared with CMV-specific
cells. CD127 expression was relatively less frequent on MTB-specific cells in HIV
co-infection. MTB-specific CD4+ T-cells PD-1 expression was infrequent in
contrast to EBV-specific CD4+ T-cells. The variation in the inherent quality of
these CD4+ T-cell responses and impact of HIV co-infection may contribute to the
timing of co-infectious diseases in HIV infection.
PMID- 26417434
TI - Cooperative and alternate functions for STIM1 and STIM2 in macrophage activation
and in the context of inflammation.
AB - Calcium (Ca(2+)) signaling in immune cells, including macrophages, controls a
wide range of effector functions that are critical for host defense and
contribute to inflammation and autoimmune diseases. However, receptor-mediated
Ca(2+) responses consist of complex mechanisms that make it difficult to identify
the pathogenesis and develop therapy. Previous studies have revealed the
importance of the Ca(2+) sensor STIM1 and store-operated Ca(2+)-entry (SOCE) for
Fcgamma-receptor activation and IgG-induced inflammation. Here, we identify the
closely related STIM2 as mediator of cell migration and cytokine production
downstream of GPCR and TLR4 activation in macrophages and show that mice lacking
STIM2 are partially resistant to inflammatory responses in peritonitis and LPS
induced inflammation. Interestingly, STIM2 modulates the migratory behavior of
macrophages independent from STIM1 and without a strict requirement for Ca(2+)
influx. While STIM2 also contributes in part to FcgammaR activation, the C5a
induced amplification of IgG-mediated phagocytosis is mainly dependent on STIM1.
Blockade of STIM-related functions limits mortality in experimental models of
AIHA and LPS-sepsis in normal mice. These results suggest benefits of Ca(2+)
inhibition for suppression of exacerbated immune reactions and illustrate the
significance of alternate functions of STIM proteins in macrophage activation and
in the context of innate immune inflammation.
PMID- 26417435
TI - BTK mutations selectively regulate BTK expression and upregulate monocyte XBP1
mRNA in XLA patients.
AB - Mutations in the Bruton agammaglobulinemia tyrosine kinase (BTK) gene are
responsible for X-linked agammaglobulinemia (XLA). Unfolded or misfolded proteins
can trigger stress pathways in the endoplasmic reticulum (ER), known as unfolded
protein response (UPR). The aim was to clarify the involvement of UPR in XLA
pathophysiology. By reverse transcription-quantitative PCR, we evaluated the
expression of BTK and 12 UPR-related genes in eight patients. Moreover, we
assessed the BTK protein expression and pattern in the patients' monocytes by
flow cytometry and fluorescence immunocytochemistry. We found a reduced BTK
expression in patients with stop codon mutations (P < 0.02). However, missense
mutations did not affect BTK expression. Flow cytometry showed a reduction of BTK
in patients which was corroborated by an absent or nonfunctional protein
synthesis revealed by immunocytochemistry. In contrast with the other UPR-related
genes, X-box binding protein 1 (XBP1) was markedly upregulated in the patients (P
< 0.01), suggesting Toll-like receptor (TLR) activation since BTK directly
interacts with TLRs as a negative regulator and XBP1 can be activated in direct
response to TLR ligation. Different BTK mutations can be identified by the BTK
expression. Inasmuch as UPR-related genes were downregulated or unaltered in
patients, we speculate the involvement of the TLRs-XBP1 axis in the XLA
pathophysiology. Such data could be the basis for further studies of this novel
pathomechanism concerning XLA.
PMID- 26417436
TI - Amaranthus leucocarpus lectin recognizes a moesin-like O-glycoprotein and
costimulates murine CD3-activated CD4(+) T cells.
AB - The Galbeta1,3GalNAcalpha1,O-Ser/Thr specific lectin from Amaranthus leucocarpus
(ALL) binds a ~70 kDa glycoprotein on murine T cell surface. We show that in the
absence of antigen presenting cells, murine CD4(+) T cells activated by an anti
CD3 antibody plus ALL enhanced cell proliferation similar to those cells
activated via CD3/CD28 at 48 h of culture. Moreover, ALL induced the production
of IL-4, IL-10, TNF-alpha, and TGF-beta in CD3-activated cells. Proteomic assay
using two-dimensional electrophoresis and far-Western blotting, ALL recognized
two prominent proteins associated to the lipid raft microdomains in CD3/CD28
activated CD4(+) T cells. By mass spectrometry, the peptide fragments from ALL
recognized proteins showed sequences with 33% homology to matricin (gi|347839
NCBInr) and 41% identity to an unnamed protein related to moesin (gi|74186081
NCBInr). Confocal microscopy analysis of CD3/CD28-activated CD4(+) T cells
confirmed that staining by ALL colocalized with anti-moesin FERM domain antibody
along the plasma membrane and in the intercellular contact sites. Our findings
suggest that a moesin-like O-glycoprotein is the ALL-recognized molecule in lipid
rats, which induces costimulatory signals on CD4(+) T cells.
PMID- 26417437
TI - IL-33 promotes MHC class II expression in murine mast cells.
AB - Mast cells (MCs), recognized as tissue-resident cells of hematopoietic origin,
are involved in cellular and pathological manifestations of allergic disorders
including atopic dermatitis. IL-33, a member of the IL-1 cytokine family,
activates Th2-type immune responses, and promotes the degranulation and
maturation of MCs. However, it is uncertain whether IL-33 treatment induces
mature mast cells to acquire the characteristics of the monocyte-dendritic cell
lineage.We investigated the effect of IL-33 on the MHC class II expression and
function of murine mast cells. IL-33-treated mature murine bone marrow-derived
mast cells (BMMCs) were analyzed by FACS, real-time PCR, chromatin
immunoprecipitation (ChIP) assay, and Western blotting. The morphology and
degranulation activity of BMMCs and T-cell activation by BMMCs were also
examined. BMMCs treated with IL-33 for 10 days induced cell surface expression of
the MHC class II protein, whereas the expression of FcepsilonRI and c-kit was not
affected by IL-33. The expression of CIITA, driven from pIII and pIV, was up
regulated in IL-33-treated BMMCs. The amount of PU.1 mRNA and protein
significantly increased in IL-33-treated BMMCs. The ChIP assay showed PU.1
binding to CIITA pIII, and enhanced histone acetylation due to IL-33 treatment.
Syngeneic T cells were activated by co-culture with IL-33-treated BMMCs, although
the expression of the co-stimulatory molecules, CD40, CD80, CD86, and PDL-1, was
not detected. Mast cells express MHC class II after prolonged exposure to IL-33,
probably due to enhanced recruitment of PU.1 to CIITA pIII, resulting in
transactivation of CIITA and MHC class II. IL-33 is an important cytokine in
allergic disorders. Mast cells have the ability to express MHC class II after
prolonged exposure to IL-33 in a murine model. IL-33 holds a key to understanding
the etiology of atopic dermatitis.
PMID- 26417438
TI - Bacterial clearance reverses a skewed T-cell repertoire induced by Salmonella
infection.
AB - Salmonella typhimurium invades the spleen, liver, and peripheral lymph nodes and
has recently been detected in the bone marrow and thymus, resulting in a reduced
thymic size and a decline in the total number of thymic cells. A specific
deletion of the double-positive cell subset has been characterized, yet the
export of mature T cells to the periphery remains normal. We analyzed Salmonella
pathogenesis regarding thymic structure and the T-cell maturation process. We
demonstrate that, despite alterations in the thymic structure, T-cell development
is maintained during Salmonella infection, allowing the selection of single
positive T-cell clones expressing particular T-cell receptor beta chains (TCR
Vbeta). Moreover, the treatment of infected mice with an antibiotic restored the
normal thymic architecture and thymocyte subset distribution. Additionally, the
frequency of TCR-Vbeta usage after treatment was comparable to that in non
infected mice. However, bacteria were still recovered from the thymus after 1
month of treatment. Our data reveal that a skewed T-cell developmental process is
present in the Salmonella-infected thymus that alters the TCR-Vbeta usage
frequency. Likewise, the post-treatment persistence of Salmonella reveals a novel
function of the thymus as a potential reservoir for this infectious agent.
PMID- 26417439
TI - Atherosclerosis severity is not affected by a deficiency in IL-33/ST2 signaling.
AB - Interleukin (IL)-33 is a cytokine of the IL-1 family, which signals through the
ST2 receptor. Previous work demonstrated that the systemic administration of
recombinant IL-33 reduces the development of atherosclerosis in apolipoprotein E
deficient (ApoE(-/-)) mice by inducing a Th1-to-Th2 shift. The objective of our
study was to examine the role of endogenous IL-33 and ST2 in atherosclerosis.
ApoE(-/-), IL-33(-/-)ApoE(-/-), and ST2(-/-)ApoE(-/-) mice were fed with a
cholesterol-rich diet for 10 weeks. Additionally, a group of ApoE(-/-) mice was
injected with a neutralizing anti-ST2 or an isotype control antibody during the
period of the cholesterol-rich diet. Atherosclerotic lesion development was
measured by Oil Red O staining in the thoracic-abdominal aorta and the aortic
sinus. There were no significant differences in the lipid-staining area of IL-33(
/-)ApoE(-/-), ST2(-/-)ApoE(-/-), or anti-ST2 antibody-treated ApoE(-/-) mice,
compared to ApoE(-/-) controls. The absence of IL-33 signaling had no major and
consistent impact on the Th1/Th2 cytokine responses in the supernatant of in
vitro-stimulated lymph node cells. In summary, deficiency of the endogenously
produced IL-33 and its receptor ST2 does not impact the development of
atherosclerosis in ApoE-deficient mice.
PMID- 26417440
TI - Testing the role of the FcgammaRIIB immunoreceptor tyrosine-based inhibitory
motif in regulation of the B cell immune response.
AB - In vitro studies have demonstrated that the immunoreceptor tyrosine-based
inhibitory motif (ITIM) of the inhibitory Fc receptor FcgammaRIIB is critical for
mediating attenuation of signaling via immunoreceptor tyrosine-based activation
motif (ITAM) containing receptors, such as the B cell antigen receptor (BCR),
when FcgammaRIIB is co-cross-linked to these activation receptors. To test the
role of the FcgammaRIIB ITIM motif in regulation of the B cell immune response in
vivo, we constructed lines of transgenic mice expressing a form of FcgammaRIIB
with an inactivating tyrosine (Y) to phenylalanine (F) mutation in the ITIM
motif. Detailed studies of one of these lines, in which the mutant FcgammaRIIB
was expressed on B cells and other cell types that normally express this
receptor, were performed. No quantitative differences in germinal center (GC) B
cell responses were observed between the mutant FcgammaRIIB transgenic line and
control mice. However, serum antibody and antibody forming cell responses were
often observed to be elevated in the ITIM mutant FcgammaRIIB transgenic mice as
compared to controls, though not to the same extent as mice deficient in
expression of FcgammaRIIB. Moreover, primary B cells from the ITIM mutant
FcgammaRIIB line did not display the same level of augmented BCR signaling as
primary FcgammaRIIB deficient B cells under conditions inducing co-cross-linking
of FcgammaRIIB and the BCR. In total, these data suggest that a functional ITIM
motif is not required for all in vivo inhibitory activity of this receptor.
However, we also found that the transgenic ITIM mutant FcgammaRIIB receptor was
expressed at abnormal levels in several hematopoietic lineages. Thus,
confirmation of our findings will require the generation and analysis of mice in
which an ITIM mutant form of FcgammaRIIB is expressed in vivo as is the
endogenous receptor.
PMID- 26417441
TI - Overexpression of Fkbp11, a feature of lupus B cells, leads to B cell tolerance
breakdown and initiates plasma cell differentiation.
AB - Systemic Lupus Erythematosus (SLE) is a severe systemic autoimmune disease,
characterized by multi-organ damages, triggered by an autoantibody-mediated
inflammation, and with a complex genetic influence. It is today accepted that
adult SLE arises from the building up of many subtle gene variations, each one
adding a new brick on the SLE susceptibility and contributing to a phenotypic
trait to the disease. One of the ways to find these gene variations consists in
comprehensive analysis of gene expression variation in a precise cell type, which
can constitute a good complementary strategy to genome wide association studies.
Using this strategy, and considering the central role of B cells in SLE, we
analyzed the B cell transcriptome of quiescent SLE patients, and identified an
overexpression of FKBP11, coding for a cytoplasmic putative peptidyl-prolyl
cis/trans isomerase and chaperone enzyme. To understand the consequences of
FKBP11 overexpression on B cell function and on autoimmunity's development, we
created lentiviral transgenic mice reproducing this gene expression variation. We
showed that high expression of Fkbp11 reproduces by itself two phenotypic traits
of SLE in mice: breakdown of B cell tolerance against DNA and initiation of
plasma cell differentiation by acting upstream of Pax5 master regulator gene.
PMID- 26417442
TI - Decreased expression of CD200R3 on mouse basophils as a novel marker for IgG1
mediated anaphylaxis.
AB - IgE-mediated mast cell activation is the trigger of anaphylaxis in humans,
whereas it is known that not only IgE but also IgG can induce anaphylaxis in
mice. In our preliminary experiments, the expression of a murine basophil
identification marker, CD200R3, on antigen-sensitized basophils decreased
following specific antigen challenge. Interestingly, this decrease did not always
correspond with increased expression of the IgE-mediated basophil activation
marker CD200R1. Since IgG as well as IgE plays a role in mouse anaphylaxis, we
hypothesized that the observed decrease in CD200R3 on basophils was caused by IgG
mediated cell activation. We attempted to establish whether CD200R3 is a marker
of IgG-mediated basophil activation and if its expression is correlated with
anaphylaxis in a mouse model. Mouse basophils were stimulated via Fc?Rs and/or
FcgammaRs, and levels of CD200R1 and CD200R3 were analyzed by flow cytometry.
Basophils derived from naive mice were challenged with a natural antigen, beta
lactoglobulin, after passive sensitization with anti-beta-LG serum or IgG/IgG
subclass-depleted antiserum. Systemic anaphylaxis was induced by i.v. injection
of anti-FcgammaRIII/II monoclonal antibody, and CD200R3 expression on peripheral
basophils was assessed. Stimulation via Fc?Rs induced a significant increase in
CD200R1 expression but had only a small effect on that of CD200R3. However, anti
FcgammaRIII/II stimulation reduced CD200R3 expression markedly. In passive
sensitization experiments, down-regulation of CD200R3 induced by antigen
challenge was strongly negated by the depletion of IgG or IgG1 from antiserum.
Intravenous injection of anti-FcgammaRIII/II induced CD200R3 down-regulation on
peripheral basophils, together with a drop in rectal temperature. Lowered CD200R3
expression on basophils is induced by IgG-mediated stimulation via FcgammaRs. Use
of CD200R1 and CD200R3 as activation markers enables the evaluation of murine
basophil activation mediated by IgE and IgG, respectively.
PMID- 26417443
TI - IL-27 and TGFbeta mediated expansion of Th1 and adaptive regulatory T cells
expressing IL-10 correlates with bacterial burden and disease severity in
pulmonary tuberculosis.
AB - CD4(+) T cell expression of IL-10 is an important mechanism controlling immunity
to tuberculosis (TB). To identify the CD4(+) T cell subsets producing IL-10 in
human TB, we enumerated the frequencies of IL-10 expressing CD4(+) T cell subsets
following TB-antigen stimulation of cells from individuals with pulmonary (PTB)
and latent TB (LTB). We first demonstrate that TB antigens induce an expansion of
IL-10 expressing Th1 (IL-10(+), IFNgamma(+), T-bet(+)), Th2 (IL-10(+), IL-4(+),
GATA-3(+)), Th9 (IL-10(+), IL-9(+), IL-4(-)), Th17 (IL-10(+), IL-17(+), IFNgamma(
)), and natural and adaptive regulatory T cells [nTregs; IL-10(+), CD4(+),
CD25(+), Foxp3(+) and aTregs; IL-10 single(+), CD4(+), CD25(-), Foxp3(-)] in PTB
and LTB individuals, with frequencies being significantly higher in the former.
However, only Th1 cells and adaptive Tregs expressing IL-10 exhibit a positive
relationship with bacterial burdens and extent of disease in PTB. Finally, we
show that IL-27 and TGFbeta play an important role in the regulation of IL-10(+)
Th cell subsets. Thus, active PTB is characterized by an IL-27 and TGFbeta
mediated expansion of IL-10 expressing CD4(+) T cell subsets, with IL-10(+) Th1
and IL-10(+) aTreg cells playing a potentially pivotal role in the pathogenesis
of active disease.
PMID- 26417444
TI - Peripheral basophil reactivity, CD203c expression by Cryj1 stimulation, is useful
for diagnosing seasonal allergic rhinitis by Japanese cedar pollen.
AB - Measuring specific IgE can yield direct, accurate, and objective data.
Nevertheless, clinical symptoms of allergy are often inconsistent with these
data. Recently, the expression of CD203c, a surface marker of basophils, has been
reported as capable of distinguishing allergic patients. This study compared
specific IgE in serum and skin tests against antigen to assess CD203c as a
biomarker correlated with allergic rhinitis (AR). We asked 3,453 subjects whether
they experienced any AR related symptom. All subjects were assessed for six
specific IgEs for common aeroallergens. Skin tests were also conducted for six
aeroallergens. We observed the reactivity of peripheral basophil by measuring the
levels of CD203c by Cryj1 stimulation using flow cytometry. Of the 3,453
participants, 1,987 (57.5%) possessed Japanese cedar pollen (JCP) specific IgE in
their serum. Among those 1,987 JCP specific IgE positive participants, 552
(27.8%) had not experienced any allergic symptom during the JCP season. The
levels of CD203c in the peripheral basophil by Cryj1 stimulation were
significantly higher in SAR-JCP subjects than in non-SAR-JCP subjects (Cryj1 0.5
ng/ml: 2.25 +/- 0.90% vs. 60.2 +/- 27.4%, p < 0.01, Cryj1 50 ng/ml: 1.89 +/-
0.90% vs. 68.0 +/- 21.2%, p < 0.01). Our results indicate that the levels of
CD203c in peripheral basophils by Cryj1 stimulation is a more objective and
reliable marker that better reflects the allergic reaction by SAR-JCP in vivo
than measuring specific IgE in serum or skin tests.
PMID- 26417445
TI - Neonatal microbial colonization in mice promotes prolonged dominance of
CD11b(+)Gr-1(+) cells and accelerated establishment of the CD4(+) T cell
population in the spleen.
AB - To assess the microbial influence on postnatal hematopoiesis, we examined the
role of early life microbial colonization on the composition of leukocyte subsets
in the neonatal spleen. A high number of CD11b(+)Gr-1(+) splenocytes present
perinatally was sustained for a longer period in conventionally colonized (CONV)
mice than in mono-colonized (MC) and germfree (GF) mice, and the CD4(+) T cell
population established faster in CONV mice. At the day of birth, compared to GF
mice, the expression of Cxcl2 was up-regulated and Arg1 down-regulated in livers
of CONV mice. This coincided with lower abundance of polylobed cells in the liver
of CONV mice. An earlier peak in the expression of the genes Tjp1, Cdh1, and JamA
in intestinal epithelial cells of CONV mice indicated an accelerated closure of
the epithelial barrier. In conclusion, we have identified an important microbiota
dependent neonatal hematopoietic event, which we suggest impacts the subsequent
development of the T cell population in the murine spleen.
PMID- 26417447
TI - Gold Nanoparticle Labeling Based ICP-MS Detection/Measurement of Bacteria, and
Their Quantitative Photothermal Destruction.
AB - Bacteria such as Salmonella and E. coli present a great challenge in public
health care in today's society. Protection of public safety against bacterial
contamination and rapid diagnosis of infection require simple and fast assays for
the detection and elimination of bacterial pathogens. After utilizing Salmonella
DT104 as an example bacterial strain for our investigation, we report a rapid and
sensitive assay for the qualitative and quantitative detection of bacteria by
using antibody affinity binding, popcorn shaped gold nanoparticle (GNPOPs)
labeling, surfance enchanced Raman spectroscopy (SERS), and inductively coupled
plasma mass spectrometry (ICP-MS) detection. For qualitative analysis, our assay
can detect Salmonella within 10 min by Raman spectroscopy; for quantitative
analysis, our assay has the ability to measure as few as 100 Salmonella DT104 in
a 1 mL sample (100 CFU/mL) within 40 min. Based on the quantitative detection, we
investigated the quantitative destruction of Salmonella DT104, and the assay's
photothermal efficiency in order to reduce the amount of GNPOPs in the assay to
ultimately to eliminate any potential side effects/toxicity to the surrounding
cells in vivo. Results suggest that our assay may serve as a promising candidate
for qualitative and quantitative detection and elimination of a variety of
bacterial pathogens.
PMID- 26417446
TI - Hyperoxia promotes polarization of the immune response in ovalbumin-induced
airway inflammation, leading to a TH17 cell phenotype.
AB - Previous studies have demonstrated that hyperoxia-induced stress and oxidative
damage to the lungs of mice lead to an increase in IL-6, TNF-alpha, and TGF-beta
expression. Together, IL-6 and TGF-beta have been known to direct T cell
differentiation toward the TH17 phenotype. In the current study, we tested the
hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell
phenotype in response to ovalbumin-induced acute airway inflammation. Airway
inflammation was induced in female BALB/c mice by intraperitoneal sensitization
and intranasal introduction of ovalbumin, followed by challenge methacholine.
After the methacholine challenge, animals were exposed to hyperoxic conditions in
an inhalation chamber for 24 h. The controls were subjected to normoxia or
aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of
hyperoxia, the number of macrophages and lymphocytes decreased in animals with
ovalbumin-induced airway inflammation, whereas the number of neutrophils
increased after ovalbumin-induced airway inflammation. The results showed that
expression of Nrf2, iNOS, T-bet and IL-17 increased after 24 of hyperoxia in both
alveolar macrophages and in lung epithelial cells, compared with both animals
that remained in room air, and animals with ovalbumin-induced airway
inflammation. Hyperoxia alone without the induction of airway inflammation lead
to increased levels of TNF-alpha and CCL5, whereas hyperoxia after inflammation
lead to decreased CCL2 levels. Histological evidence of extravasation of
inflammatory cells into the perivascular and peribronchial regions of the lungs
was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes
polarization of the immune response toward the TH17 phenotype, resulting in
tissue damage associated with oxidative stress, and the migration of neutrophils
to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin-induced
acute airway inflammation is relevant to preventing or treating asthmatic
patients that require oxygen supplementation to reverse the hypoxemia.
PMID- 26417448
TI - Microbeads-Guided Reconstruction of 3D Osteocyte Network during Microfluidic
Perfusion Culture.
AB - Osteocytes reside as 3-dimensionally networked cells in the lacunocanalicular
structure of bones, and function as the master regulators of homeostatic bone
remodeling. We report here, for the first time to our best knowledge, the use of
a biomimetic approach to reconstruct the 3D osteocyte network with physiological
relevant microscale dimensions. In this approach, biphasic calcium phosphate
microbeads were assembled with murine early osteocytes (MLO-A5) to provide an
initial mechanical framework for 3D network formation and maintenance during long
term perfusion culture in a microfluidic chamber. The microbead size of 20-25 MUm
was used to: (1) facilitate a single cell to be placed within the interstitial
space between the microbeads, (2) mitigate the proliferation of the entrapped
cell due to its physical confinement in the interstitial site, and (3) control
cell-to-cell distance to be 20-25 MUm as observed in murine bones. The entrapped
cells formed a 3D cellular network by extending and connecting their processes
through openings between the microbeads within 3 days of culture. The entrapped
cells produced significant mineralized extracellular matrix to fill up the
interstitial spaces, resulting in the formation of a dense tissue structure
during the course of 3-week culture. We found that the time-dependent osteocytic
transitions of the cells exhibited trends consistent with in vivo observations,
particularly with high expression of Sost gene, which is a key osteocyte-specific
marker for the mechanotransduction function of osteocytes. In contrast, cells
cultured in 2D well-plates did not replicate in vivo trends. These results
provide an important new insight in building physiologically relevant in vitro
bone tissue models.
PMID- 26417449
TI - Diffusion properties of inkjet printed ionic self-assembling polyelectrolyte
hydrogels.
AB - In the present work, Crank's model was used to characterize solute transport in
inkjet printed polyelectrolyte gels. The diffusion of a small charged molecule
(fluorescein), various size linear uncharged molecules (dextrans), and a globular
protein (albumin) in printed PSS-PDDA with near stoichiometric composition
happened respectively at about 10-8, 10-9, and 10-10 cm2/sec. Polyelectrolyte
complexes printed with non-stoichiometric ratios were found to be non-equilibrium
structures consisting of three populations of polymer chains: fully complexed
chains, chains in partial electrostatic interaction with the complex, and chains
in excess having minimal interaction with the complex. This structure may be
multiple phases. The applicability of hydrodynamic and free volume models to
describe transport in printed polyelectrolyte gels was discussed.
PMID- 26417450
TI - Canadian Pediatric Weight Management Registry (CANPWR): baseline descriptive
statistics and comparison to Canadian norms.
AB - BACKGROUND: A pilot study was conducted to assess the feasibility of establishing
a multi-site CANadian Pediatric Weight management Registry (CANPWR) containing
individual, family and weight management program information. METHODS:
Standardized baseline data were collected to characterize CANPWR participants (n
= 310) in comparison to a sample of age-matched Canadian children measured in the
nationally representative Canadian Health Measures Survey (CHMS; n = 3,788). This
study compared demographic, anthropometric, cardiometabolic and lifestyle
characteristics of participants (aged 6-17 years) in the CANPWR pilot study with
those from the CHMS. RESULTS: Compared to CHMS respondents, CANPWR participants
had higher BMI z-score, waist circumference, blood pressure, total cholesterol,
LDL cholesterol, triglycerides and fasting glucose, and lower HDL cholesterol.
They reported lower sugared drink consumption, were more likely to be non-white
and had parents with lower education. CONCLUSIONS: The CANPWR cohort represents a
group that has biological and behavioral profiles that place them at increased
health risk and who differ significantly from typical Canadians of the same age.
PMID- 26417451
TI - A protocol for developing an evaluation framework for an academic and private
sector partnership to assess the impact of major food and beverage companies'
investments in community health in the United States.
AB - Public health leaders increasingly recognize the importance of multi-sector
partnerships and systems approaches to address obesity. Public-private
partnerships (PPP), which are joint ventures between government agencies and
private sector entities, may help facilitate this process, but need to be
delivered through comprehensive, transparent frameworks to maximize potential
benefits and minimize potential risks for all partners. The City University of
New York (CUNY) School of Public Health and the Healthy Weight Commitment
Foundation (HWCF) propose to engage in a unique academic-private-sector research
partnership to evaluate the impact and effectiveness of the food and beverage
industry's investment in obesity and hunger prevention and reduction through
community-level healthful eating and active living programs. The CUNY-HWCF
academic-private partnership protocol described here incorporates best practices
from the literature on PPP into the partnership's design. The CUNY-HWCF
partnership design demonstrates how established guidelines for partnership
components will actively incorporate and promote the principles of successful
PPPs identified in various research papers. These identified principles of
successful PPP, including mutuality (a reciprocal relationship between entities),
and equality among partners, recognition of partners' unique strengths and roles,
alignment of resources and expertise toward a common cause, and coordination and
delegation of responsibilities, will be embedded throughout the design of
governance, management, funding, intellectual property and accountability
structures. The CUNY-HWCF partnership responds to the call for increased multi
sector work in obesity prevention and control. This framework aims to promote
transparency and the shared benefits of complementary expertise while minimizing
shared risks and conflicts of interest. This framework serves as a template for
future academic-private research partnerships.
PMID- 26417452
TI - Endothelial Cell Loss after Phacoemulsification according to Different Anterior
Chamber Depths.
AB - Purpose. To compare the loss of corneal endothelial cells after
phacoemulsification according to different anterior chamber depths (ACDs).
Methods. We conducted a prospective study on 135 eyes with senile cataracts. Eyes
with nuclear density grades of 2 to 4 were divided into three groups according to
ACD: ACD I, 1.5 < ACD <= 2.5 mm; ACD II, 2.5 < ACD <= 3.5 mm; or ACD III, 3.5 <
ACD <= 4.5 mm. Intraoperative mean cumulative dissipated energy (CDE) was
measured. Clinical examinations included central corneal thickness (CCT) and
endothelial cell count (ECC) preoperatively and 2 months postoperatively.
Results. There were no significant differences in CDE among the ACD groups (P >
0.05). Endothelial cell loss was significantly higher in ACD I than in ACD III in
grades 3 and 4 cataract density groups 2 months after phacoemulsification (P <
0.05). There were also more changes in CCT in all of the cataract density groups
in the ACD I group compared to the ACD II and III groups 2 months
postoperatively, but the difference was not statistically significant.
Conclusions. Eyes with shallow ACDs, especially those with relatively hard
cataract densities, can be vulnerable to more corneal endothelial cell loss in
phacoemulsification surgery.
PMID- 26417454
TI - Reproductive and Obstetric Factors Are Key Predictors of Maternal Anemia during
Pregnancy in Ethiopia: Evidence from Demographic and Health Survey (2011).
AB - Anemia is a major public health problem worldwide. In Ethiopia, a nationally
representative and consistent evidence is lacking on the prevalence and
determinants during pregnancy. We conducted an in-depth analysis of demographic
and health survey for the year 2011 which is a representative data collected from
all regions in Ethiopia. Considering maternal anemia as an outcome variable,
predicting variables from sociodemographic, household, and reproductive/obstetric
characteristics were identified for analyses. Logistic regression model was
applied to identify predictors at P < 0.05. The prevalence of anemia among
pregnant women was 23%. Maternal age, region, pregnancy trimester, number of
under five children, previous history of abortion (termination of pregnancy),
breastfeeding practices, and number of antenatal care visits were key independent
predictors of anemia during pregnancy. In conclusion, the level of anemia during
pregnancy is a moderate public health problem in Ethiopia. Yet, special
preventive measures should be undertaken for pregnant women who are older in age
and having too many under five children and previous history of abortion. Further
evidence is expected to be generated concerning why pregnant mothers from the
eastern part of the country and those with better access to radio
disproportionately develop anemia more than their counterparts.
PMID- 26417453
TI - Anti-VEGF Therapy and the Retina: An Update.
AB - Ocular angiogenesis and macular oedema are major causes of sight loss across the
world. Aberrant neovascularisation, which may arise secondary to numerous disease
processes, can result in reduced vision as a result of oedema, haemorrhage, and
scarring. The development of antivascular endothelial growth factor (anti-VEGF)
agents has revolutionised the treatment of retinal vasogenic conditions. These
drugs are now commonly employed for the treatment of a plethora of ocular
pathologies including choroidal neovascularisation, diabetic macular oedema, and
retinal vein occlusion to name a few. In this paper, we will explore the current
use of anti-VEGF in a variety of retinal diseases and the impact that these
medications have had on visual outcome for patients.
PMID- 26417455
TI - How Predictable Is the Operative Time of Laparoscopic Surgery for Ovarian
Endometrioma?
AB - Endometriosis is a tricky albeit common disease whose management largely relies
on laparoscopy. We have studied the operative times of laparoscopic endometrioma
surgery in order to assess their predictability and possible predictors. One
hundred forty-eight laparoscopies were included, with a median operative time of
70 minutes (mean 75.14; 95% CI: 70.03-80.24). Half of the cases had a duration
within 15-20 minutes above or below the median (IQR: 55-93.75), but the whole
dataset ranged from 20 to 180 minutes, and the standard deviation was relatively
large (31.4). Surgical times were significantly related to technical (number and
size of the cysts) and nontechnical factors (age, parity, dysmenorrhea, and
family history). At multiple logistic regression, after adjusting for number and
size of the cysts, surgical times below the first quartile were associated with
older age (>30 years old: aOR: 3.590; 95% CI: 1.417-9.091) and parity (>=1
delivery: aOR: 3.409; 95% CI: 1.343-8.651). Longer times, above the third
quartile, were instead predicted by a familial anamnesis of endometriosis (aOR:
3.639; 95% CI: 1.246-10.627). Our findings indicate highly variable surgical
times, which are predicted by unexpected nontechnical factors. This is consistent
with the complexity of endometriosis and its treatment. Productivity and
efficiency in endometriosis surgery should focus on the quality of healthcare
outcomes rather than on the time spent in the operating theatres.
PMID- 26417456
TI - Analysis of AKAP7gamma Dimerization.
AB - A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins
that contribute to spatiotemporal regulation of PKA-mediated phosphorylation
events. In particular, AKAP7 is a family of alternatively spliced proteins that
participates in cardiac calcium dynamics. Here, we demonstrate via pull-down from
transfected cells and by direct protein-protein association that AKAP7gamma self
associates. Self-association appears to be an isoform specific phenomenon, as
AKAP7alpha did not associate with itself or with AKAP7gamma. However, AKAP7gamma
did associate with AKAP7delta, suggesting the long isoforms of the AKAP can form
heterodimers. Surface plasmon resonance found that the AKAP7gamma self
association occurs via two high affinity binding sites with K D values in the low
nanomolar range. Mapping of the binding sites by peptide array reveals that
AKAP7gamma interacts with itself through multiple regions. Photon counting
histogram analysis (PCH) of AKAP7gamma-EGFP expressed in HEK-293 cells confirmed
that AKAP7gamma-EGFP self-associates in a cellular context. Lastly, computational
modeling of PKA dynamics within AKAP7gamma complexes suggests that
oligomerization may augment phosphorylation of scaffolded PKA substrates. In
conclusion, our study reveals that AKAP7gamma forms both homo- and heterodimers
with the long isoforms of the AKAP and that this phenomenon could be an important
step in mediating effective substrate phosphorylation in cellular microdomains.
PMID- 26417457
TI - Coincidence Anticipation Timing Performance during an Acute Bout of Brisk Walking
in Older Adults: Effect of Stimulus Speed.
AB - This study examined coincidence anticipation timing (CAT) performance at slow and
fast stimulus speeds before, during, and after an acute bout of walking in adults
aged 60-76 years. Results from a series of repeated measures ANOVAs indicated
significant rest versus exercise * stimulus speed * time interactions for
absolute and variable errors (both P = 0.0001) whereby absolute and variable
error scores, when stimulus speed was slow, improved as the duration of exercise
increased. When stimulus speed was fast there were significantly greater absolute
and variable errors at 18 minutes of the walking bout. There was also greater
error at 18 minutes during walking compared to rest. These results suggest that,
in a task involving walking and CAT, stimulus speeds plays an important role;
specifically walking (exercise) enhances CAT performance at slow stimulus speeds
but reduces CAT performance at fast stimulus speeds. The implications are that in
everyday situations, where events require dual-task responses to be made at
different speeds, for example, walking on the pavement whilst avoiding a crowd,
compared to crossing a busy road, an understanding of how different stimulus
speeds influence dual-task performance is extremely important, particularly in
the older adult population.
PMID- 26417458
TI - Age-Related Reduced Somatosensory Gating Is Associated with Altered Alpha
Frequency Desynchronization.
AB - Sensory gating (SG), referring to an attenuated neural response to the second
identical stimulus, is considered as preattentive processing in the central
nervous system to filter redundant sensory inputs. Insufficient somatosensory SG
has been found in the aged adults, particularly in the secondary somatosensory
cortex (SII). However, it remains unclear which variables leading to the age
related somatosensory SG decline. There has been evidence showing a relationship
between brain oscillations and cortical evoked excitability. Thus, this study
used whole-head magnetoencephalography to record responses to paired-pulse
electrical stimulation to the left median nerve in healthy young and elderly
participants to test whether insufficient stimulus 1- (S1-) induced event-related
desynchronization (ERD) contributes to a less-suppressed stimulus 2- (S2-) evoked
response. Our analysis revealed that the minimum norm estimates showed age
related reduction of SG in the bilateral SII regions. Spectral power analysis
showed that the elderly demonstrated significantly reduced alpha ERD in the
contralateral SII (SIIc). Moreover, it was striking to note that lower S1-induced
alpha ERD was associated with higher S2-evoked amplitudes in the SIIc among the
aged adults. Conclusively, our findings suggest that age-related decline of
somatosensory SG is partially attributed to the altered S1-induced oscillatory
activity.
PMID- 26417459
TI - Restoration of Central Programmed Movement Pattern by Temporal Electrical
Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy.
AB - Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist
muscle pairs during fast goal-directed movements have been found in patients with
hypermetria. Since peripheral electrical stimulation (ES) and motor training may
modulate motor cortical excitability through plasticity mechanisms, we aimed to
investigate whether temporal ES-assisted movement training could influence
premovement cortical excitability and alleviate hypermetria in patients with
spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis
muscle and antagonist flexor carpi radialis muscle, premovement motor evoked
potentials (MEPs) of the flexor carpi radialis muscle, and the constant and
variable errors of movements were assessed before and after 4 weeks of ES
assisted fast goal-directed wrist extension training in the training group and of
general health education in the control group. After training, the premovement
MEPs of the antagonist muscle were facilitated at 50 ms before the onset of
movement. In addition, the EMG onset latency of the antagonist muscle shifted
earlier and the constant error decreased significantly. In summary, temporal ES
assisted training alleviated hypermetria by restoring antagonist premovement and
temporal triphasic EMG patterns in SCA patients. This technique may be applied to
treat hypermetria in cerebellar disorders. (This trial is registered with
NCT01983670.).
PMID- 26417461
TI - An Influence of Birth Weight, Gestational Age, and Apgar Score on Pattern Visual
Evoked Potentials in Children with History of Prematurity.
AB - PURPOSE: The objective of our study was to examine a possible influence of
gestational age, birth weight, and Apgar score on amplitudes and latencies of
P100 wave in preterm born school-age children. MATERIALS AND METHODS: We examined
the following group of school-age children: 28 with history of prematurity (mean
age 10.56 +/- 1.66 years) and 25 born at term (mean age 11.2 +/- 1.94 years). The
monocular PVEP was performed in all children. RESULTS: The P100 wave amplitudes
and latencies significantly differ between preterm born school-age children and
those born at term. There was an essential positive linear correlation of the
P100 wave amplitudes with birth weight, gestational age, and Apgar score. There
were the negative linear correlations of P100 latencies in 15-minute stimulation
from O1 and Oz electrode with Apgar score and O1 and O2 electrode with
gestational age. CONCLUSIONS: PVEP responses vary in preterm born children in
comparison to term. Low birth weight, early gestational age, and poor baseline
output seem to be the predicting factors for the developmental rate of a brain
function in children with history of prematurity. Further investigations are
necessary to determine perinatal factors that can affect the modified visual
system function in preterm born children.
PMID- 26417460
TI - Neural Plastic Effects of Cognitive Training on Aging Brain.
AB - Increasing research has evidenced that our brain retains a capacity to change in
response to experience until late adulthood. This implies that cognitive training
can possibly ameliorate age-associated cognitive decline by inducing training
specific neural plastic changes at both neural and behavioral levels. This
longitudinal study examined the behavioral effects of a systematic thirteen-week
cognitive training program on attention and working memory of older adults who
were at risk of cognitive decline. These older adults were randomly assigned to
the Cognitive Training Group (n = 109) and the Active Control Group (n = 100).
Findings clearly indicated that training induced improvement in auditory and
visual-spatial attention and working memory. The training effect was specific to
the experience provided because no significant difference in verbal and visual
spatial memory between the two groups was observed. This pattern of findings is
consistent with the prediction and the principle of experience-dependent
neuroplasticity. Findings of our study provided further support to the notion
that the neural plastic potential continues until older age. The baseline
cognitive status did not correlate with pre- versus posttraining changes to any
cognitive variables studied, suggesting that the initial cognitive status may not
limit the neuroplastic potential of the brain at an old age.
PMID- 26417462
TI - Buschke-Lowenstein Tumour: Successful Treatment with Minimally Invasive
Techniques.
AB - We report a case of an 80-year-old female who presented with a four-year history
of a growing mass in the perianal area with pain and bleeding during defaecation.
Clinical examination revealed a locally destructive, cauliflower-like, verrucous
mass measuring 10 * 12 cm in diameter. Histologic findings revealed a moderate
degree of dysplasia of the epithelium with koilocytosis atypia, acanthosis, and
parakeratosis, features that are consistent with Buschke-Lowenstein tumour.
Polymerase-chain-reaction assay for human papillomavirus (HPV) showed an
infection with HPV type 11. Full-thickness excision of involved skin was
undertaken by cryotherapy and electrocautery over five months. The entire wound
was left open to heal by secondary intention. After 3 years of follow-up, the
patient has not experienced a recurrence, with excellent functional results, but
the cosmetic results were satisfactory. These minimally invasive techniques can
be safer and more cost-effective than surgery and the General Practitioner can
play a key role in diagnosis.
PMID- 26417463
TI - Different Cardiac Anomalies in Mother and Son with 4q-Syndrome.
AB - We report a female patient with asymptomatic cor triatriatum sinister, associated
with 4q34.3 deletion. Her child, carrying the same imbalance, suffers from
tetralogy of Fallot. To the best of our knowledge, this is the first reported
case of cor triatriatum associated with deletion of the long arm of the
chromosome 4; furthermore, the majority of patients with chromosome 4 long arm
syndrome have de novo deletions and only few familial cases have been reported so
far.
PMID- 26417465
TI - Enterococcus hirae Bacteremia Associated with Acute Pancreatitis and Septic
Shock.
AB - Infection with Enterococcus hirae has rarely been reported in humans but is not
uncommon in mammals and birds. We describe a case of Enterococcus hirae
bacteremia associated with acute pancreatitis, acute cholecystitis, and septic
shock responsive to antibiotic therapy and supportive critical care management.
Unique aspects of this case of Enterococcus hirae bacteremia are its association
with acute pancreatitis and its geographical origin. To our knowledge, this is
the first report of Enterococcus hirae bacteremia occurring in a patient in the
United States. Although human infection with this organism appears to be rare,
all cases reported to date describe bacteremia associated with severe and life
threatening illness. Thus, physicians need to be cognizant of the clinical
significance of this heretofore little recognized pathogen.
PMID- 26417464
TI - MALT Lymphoma of the Bladder: A Case Report and Review of the Literature.
AB - The presentation of a MALT lymphoma in the bladder is exceedingly rare.
Furthermore, the optimal treatment of primary MALT confined to the bladder
remains to be defined. Here, we report a case of a 65-year-old female with
primary MALT lymphoma treated with definitive radiation therapy. The patient
received a total dose of 30 Gy in 20 equal daily fractions to the bladder and
tolerated the treatment well. In addition, we have extensively reviewed the
relevant literature to better define the optimal management of this rare disease.
In conclusion, primary MALT lymphoma of the bladder represents a rare malignancy
with excellent prognosis if detected at an early stage. For early stage disease,
definitive radiation represents an excellent treatment modality with a minimal
side-effect profile.
PMID- 26417467
TI - Posterior Cortical Atrophy Presenting with Superior Arcuate Field Defect.
AB - An 80-year-old female with reading difficulty presented with progressive arcuate
field defect despite low intraocular pressure. Over a 5-year period, the field
defect evolved into an incongruous homonymous hemianopia and the repeated
neuroimaging revealed progressive posterior cortical atrophy. Further
neuropsychiatric assessment demonstrated symptoms and signs consistent with
Benson's syndrome.
PMID- 26417466
TI - Fetomaternal Hemorrhage following Placement of an Intrauterine Pressure Catheter:
Report of a New Association.
AB - Fetomaternal hemorrhage (FMH) can be associated with significant perinatal
mortality. Our review of the literature did not identify any cases of FMH
following placement of an intrauterine pressure catheter (IUPC). In our case, an
IUPC was inserted in a patient undergoing induction of labor at term. Fetal
bradycardia ensued shortly after placement, warranting an emergent cesarean
delivery. Severe neonatal anemia was identified, and evaluation of maternal blood
was consistent with massive FMH. This is the first reported association between
FMH and IUPC placement. If this relationship is validated in future reports,
appropriate changes in clinical practice may be warranted.
PMID- 26417468
TI - Massive Localized Lymphedema Arising from Abdominal Wall: A Case Report and
Review of the Literature.
AB - Massive localized lymphedema (MLL) is a rare pseudosarcomatous lesion due to
localized lymphatic obstruction from variable causes. It is most common on medial
aspect of thigh and inguinal region. Abdominal localization is rare and may cause
clinical diagnostic confusion with other malignant tumors due to its large size.
We report a case of abdominal wall MLL of a 56-year-old male patient under
clinical suspicion of well differentiated liposarcoma. The literature search and
differential diagnosis will be addressed. In doubt cases, immunohistochemical
stain or fluorescent in situ hybridization can help to separate this entity from
the other mimickers.
PMID- 26417469
TI - Severe Burns and Amputation of Both Arms in the First Psychotic Episode of a
Schizophrenic Patient.
AB - An alleged reduction of sensitivity to pain in people with schizophrenia has been
reported, but the nature of this complex phenomenon has not been elucidated yet.
Reports of insensitivity to burns from people with schizophrenia are extremely
rare. We report the case of a 24-year-old man who set both of his arms on fire
during the first break of paranoid schizophrenia. As a result of severe tissue
damage, both of his limbs had to be amputated. Today, at the age of 59, the
patient is physically and mentally rehabilitated and is adherent to treatment.
Additionally, given the uncertainty about the true nature of the alleged
hypoalgesia in schizophrenia, we postulate the need for a comprehensive
phenomenological approach in the study of embodiment in people with this
condition.
PMID- 26417471
TI - Lornoxicam Side Effects May Lead to Surgical Mismanagement, in Case of
Postoperative Intra-Abdominal Collection: A Case Report and Literature Review.
AB - Postoperative collection is a known complication of abdominal surgery, especially
after major surgery; however, minor surgical procedures may also be associated
with this phenomenon. Utilization of nonsteroidal anti-inflammatory drugs, such
as lornoxicam, and the adverse effects thereof, may affect the surgeon's judgment
regarding the need for, and extent of, draining of these collections. Here I
report the case of a 25-year-old male who presented with perforated acute
retrocaecal subhepatic appendicitis complicated by pleural effusion and a small
abdominal collection. The pleural effusion resolved almost completely over time.
However, the patient showed incomplete recovery, as demonstrated by nausea,
vomiting, and mood disturbance along with abdominal pain, tachycardia, and a
persistent small abdominal collection. We initially suspected infection caused by
a highly virulent type of bacteria and planned to perform percutaneous drainage.
However, owing to skin erythematic changes, administration of lornoxicam was
ceased, which resulted in complete recovery of the symptoms and consequently in
avoidance of unnecessary invasive intervention to drain the abdominal collection.
These findings suggest that the utilization and adverse effects of some
painkillers for postoperative pain, such as lornoxicam, may affect the surgeon's
judgment regarding the most appropriate surgical workup in cases of postoperative
fluid collection.
PMID- 26417470
TI - Right Heart Transvalvular Embolus with High Risk Pulmonary Embolism in a Recently
Hospitalized Patient: A Case Report of a Therapeutic Challenge.
AB - Thrombus-in-transit is not uncommon in pulmonary embolism but Right Heart
Transvalvular Embolus (RHTVE) complicating this is rare. A 54-year-old obese male
with recent hospitalization presented with severe dyspnea and collapse. Initial
investigations revealed elevated d-dimer and troponin. CTA showed saddle
pulmonary embolus and bedside echocardiogram revealed right ventricular (RV)
pressure overload and dilatation (RV > 41 mm), McConnell's sign, and mobile
echodensity attached to tricuspid valve. Patient was immediately resuscitated and
promptly transferred for surgical embolectomy under cardiopulmonary bypass. A
long segment of embolus traversing through the tricuspid valve and extensive
bilateral pulmonary artery embolus were removed. IVC filter was placed for a
persistent right lower extremity DVT. Hypercoagulable work-up was negative.
Patient continued to do well after discharge on Coumadin. Open embolectomy offers
great promises where there is no consensus in optimal management approach in such
patients. Bedside echocardiogram is vital in risk stratification and deciding
choice of advanced PE treatment.
PMID- 26417472
TI - Extraperitoneally Ruptured, Everted, and Prolapsed Bladder: A Very Rare
Complication of Pelvic Injury.
AB - Traumatic rupture of the bladder with eversion and protrusion via the perineum is
a rare complication of pelvic injury. We present a 36-year-old lady who sustained
severe pelvic injury with a bleeding right-sided deep perineal laceration. She
had closed reduction of pelvic fracture with pelvic banding and primary closure
of perineal laceration at a private hospital. She subsequently had dehiscence of
repaired perineal laceration with protrusion of fleshy mass from vulva and
leakage of urine per perineum five weeks later. Examination revealed a fleshy
mucosa-like mass protruding anteriorly with a bridge of tissue between it and
right anterolateral vaginal wall. Upward pressure on this mass revealed the
bladder neck and ureteric orifices. She had perineal and pelvic exploration with
findings of prolapsed, completely everted bladder wall through a transverse
anterior bladder wall rent via the perineum, and an unstable B1 pelvic
disruption. She had repair of the ruptured, everted, and prolapsed bladder,
double-plate and screw fixation of disrupted pelvis and repair of the
pelvic/perineal defect. She commenced physiotherapy and ambulation a week after
surgery. Patient now walks normally and is continent of urine. We conclude that
the intrinsic urethral continent mechanism plays a significant role in
maintaining continence in females.
PMID- 26417473
TI - Psychopathology in Substance Use Disorder Patients with and without Substance
Induced Psychosis.
AB - Background. Substance-induced psychotic disorder (SIPD) is a diagnosis
constructed to distinguish substance-induced psychotic states from primary
psychotic disorders. A number of studies have compared SIPD persons with primary
psychotic patients, but there is little data on what differentiates substance use
disorder (SUD) individuals with and without SIPD. Here, we compared
psychopathology, sociodemographic variables, and substance use characteristics
between SUD patients with and without SIPD. Methods. A retrospective chart review
was conducted on newly admitted patients at a rehabilitation centre between 2007
and 2012. Results. Of the 379 patients included in the study, 5% were diagnosed
with SIPD (n = 19) and 95% were diagnosed with SUDs without SIPD (n = 360). More
SIPD patients reported using cannabis and psychostimulants, and fewer SIPD
patients reported using alcohol than SUDs patients without SIPD. SIPD patients
scored higher on the "schizophrenia nuclear symptoms" dimension of the SCL-90R
psychoticism scale and exhibited more ClusterB personality traits than SUD
patients without SIPD. Discussion. These data are consistent with previous
studies suggesting that psychopathology, substance type, and sociodemographic
variables play important role in the development of SIPD. More importantly, the
results highlight the need for paying greater attention to the types of self
reported psychotic symptoms during the assessment of psychotomimetic effects
associated with psychoactive substances.
PMID- 26417474
TI - Pediatric Patient and Parental Anxiety and Impressions Related to Initial
Gastrointestinal Endoscopy: A Japanese Multicenter Questionnaire Study.
AB - Objective. To assess anxiety among pediatric patients and their parents related
to initial gastrointestinal endoscopy. Methods. Patients aged <19 years
undergoing initial gastrointestinal (GI) endoscopy and their parents were invited
to complete a self-administered questionnaire related to endoscopy in 13
institutions in Japan. Results. The subjects were 128 children, aged 1 month to
17 years. Forty-eight patients (37.5%) underwent esophagogastroduodenoscopy
(EGD), 32 (25%) underwent colonoscopy (CS), 39 (30.5%) underwent both EGD and CS,
3 (2.3%) underwent balloon enteroscopy (BE), 3 (2.3%) underwent capsule endoscopy
(CE), and 3 (2.3%) underwent CE and other endoscopic procedures. In the
preendoscopy questionnaire, the most common concerns of the patients and parents
before undergoing the procedure were "Pain" (45% of the patients underwent EGD or
BE via the oral approach, and 52% of the patients underwent CS or BE via the anal
approach) and "Procedural accidents related to the endoscopy" (63% of parents).
In the postendoscopy questionnaire, the most common difficulty that patients and
parents actually experienced before and after undergoing the procedure was
"Hunger." Conclusion. A preparatory intervention including an explanation
regarding specific concerns before initial GI endoscopy, which this study
revealed, could reduce anxiety experienced by both pediatric patients and
parents.
PMID- 26417475
TI - Human cadaveric dissection: a historical account from ancient Greece to the
modern era.
AB - The review article attempts to focus on the practice of human cadaveric
dissection during its inception in ancient Greece in 3rd century BC, revival in
medieval Italy at the beginning of 14th century and subsequent evolution in
Europe and the United States of America over the centuries. The article
highlights on the gradual change in attitude of religious authorities towards
human dissection, the shift in the practice of human dissection being performed
by barber surgeons to the anatomist himself dissecting the human body and the
enactment of prominent legislations which proved to be crucial milestones during
the course of the history of human cadaveric dissection. It particularly
emphasizes on the different means of procuring human bodies which changed over
the centuries in accordance with the increasing demand due to the rise in
popularity of human dissection as a tool for teaching anatomy. Finally, it
documents the rise of body donation programs as the source of human cadavers for
anatomical dissection from the second half of the 20th century. Presently
innovative measures are being introduced within the body donation programs by
medical schools across the world to sensitize medical students such that they
maintain a respectful, compassionate and empathetic attitude towards the human
cadaver while dissecting the same. Human dissection is indispensable for a sound
knowledge in anatomy which can ensure safe as well as efficient clinical practice
and the human dissection lab could possibly be the ideal place to cultivate
humanistic qualities among future physicians in the 21st century.
PMID- 26417477
TI - Regional differences in the density of Langerhans cells, CD8-positive T
lymphocytes and CD68-positive macrophages: a preliminary study using elderly
donated cadavers.
AB - To provide a better understanding of the local immune system in the face and
external genitalia, i.e., the oral floor, lower lip, palpebral conjunctiva, anus
and penis, we examined the distribution and density of CD1a-positve Langerhans
cells, CD8-positive suppressor T lymphocytes and CD68-positive macrophages using
specimens from 8 male elderly cadavers. The density of Langerhans cells showed an
individual difference of more than (or almost) 10-fold in the lip (oral floor).
In the oral floor, Langerhans cells were often spherical. Submucosal or
subcutaneous suppressor lymphocytes, especially rich in the oral floor and penile
skin, migrated into the epithelium at 4 sites, except for the anus. In the
conjunctiva, macrophage migration into the epithelium was seen in all 8
specimens. The density of suppressor lymphocytes showed a significant correlation
between the oral floor and the lip (r=0.78). In contrast, the anal and penile
skins showed no positive correlation in the density of all three types of
immunoreactive cells examined. Overall, irrespective of the wide individual
differences, the oral floor and conjunctiva seemed to be characterized by a rich
content of all three cell types, whereas the penile skin was characterized by an
abundance of suppressor lymphocytes. Based on the tables, as mean value, the
relative abundance of three different cell types were as follows; CD1a-positive
Langerhans cells (anus), CD8-positive lymphocytes (penis), and CD68-positive
macrophages (lip). The present observations suggest that the local immune
response is highly site-dependent, with a tendency for tolerance rather than
rejection.
PMID- 26417478
TI - Nfic regulates tooth root patterning and growth.
AB - Molecular interactions between epithelium and mesenchyme are important for root
formation. Nuclear factor I-C (Nfic) has been identified as a key regulator of
root formation. However, the mechanisms of root formation and their interactions
between Hertwig's epithelial root sheath (HERS) and mesenchyme remain unclear. In
this study, we investigated the role of Nfic in root patterning and growth during
molar root development. The molars of Nfic knockout mice exhibited an enlarged
pulp chamber and apical displacement of the pulpal floor, characteristic features
of taurodontism, due to delayed furcation formation. In developing molar roots of
mutant mice at P14, BrdU positive cells decreased in the apical mesenchyme of the
elongation region whereas those cells increased in the dental papilla of the
furcation region. Whereas cytokeratin 14 and laminin were localized in HERS cells
of mutant molars, Smoothened (Smo) and Gli1 were downregulated in
preodontoblasts. In contrast, cytokeratin 14 and Smo were localized in the cells
of the furcation region of mutant molars. These results indicate that Nfic
regulates cell proliferation in the dental mesenchyme and affects the fate of
HERS cells in a site-specific manner. From the results, it is suggested that Nfic
is required for root patterning and growth during root morphogenesis.
PMID- 26417476
TI - Differentiation of adipose-derived stem cells into Schwann-like cells: fetal
bovine serum or human serum?
AB - Access to autologous Schwann cells is limited due to lack of donor site and its
difficult isolation and culture. Therefore, one of the possible ways to obtain to
Schwann cells is to differentiate mesenchymal stem cells into glial pathway using
various materials and protocols. The aim of this study was to compare the effects
of fetal bovine serum and human serum on Schwann cell differentiation of adipose
derived stem cells to choose the best serum for use in future research. For this
purpose, after isolation of human adipose-derived stem cells, it was
characterized and differentiated into Schwann cell lineage using two protocols
which one of them contained fetal bovine serum and the other human serum. At the
end, morphological evaluation declared an increased detachment of cells in
response to human serum. On the other side, immunocytochemistry showed that there
was a significant increase in the number of cells expressing glial fibrillary
acidic proteins and S100 in fetal bovine serum-treated group when compared to
human serum-treated one (P<0.05). It was concluded that fetal bovine serum was
more effective than allogeneic human serum in Schwann cell differentiation of
adipose-derived stem cells.
PMID- 26417479
TI - Morphological study of styloid process of the temporal bone and its clinical
implications.
AB - The objective of this study was to study the morphometry of the styloid process
of temporal bone and prevalence of elongated styloid process. The morphology of
elongated styloid process along with its embryological and clinical importance
are discussed. The present study included 110 human dry skulls which were
procured from the bone collections of the department of anatomy. The styloid
process was observed macroscopically on both sides of all the skulls, the
elongations if any were noted. All the styloids were measured for their length,
thickness at different levels and interstyloid distance at various levels. Out of
110 specimens, only 5 skulls (4.5%) exhibited the elongated styloid process.
Among them, 3 skulls (2.7%) had unilateral elongation and 2 skulls (1.8%) had
bilateral elongation of the styloid process. The mean length of the styloid
process was 17.8+/-9.3 mm and 18.2+/-5.6 mm for the right and left sides,
respectively. The prevalence of elongated styloid process in the present study
was 4.5%. The clinical anatomy of this congenital variant is important to the
neurosurgeon and radiologist, while interpreting the computed tomogram and
magnetic resonance image scans. The morphological knowledge of elongated styloid
process is clinically important since the course of the vertebral artery may be
distorted in such situations.
PMID- 26417480
TI - Rectus and oblique muscles of eyeball: a morphometric study of Indian population.
AB - During the strengthening and weakening procedures of intraocular muscles,
distance of insertion from the sclerocorneal junction is an important determinant
in the identification of muscles. During repositioning of the aponeurosis of the
muscles, it is desired that the width should not change in order to avoid
diversion of forces. Available anatomic studies on insertions of extraocular
muscles are few, date back to early twentieth century and have been conducted on
mostly white population. The present study is an attempt to document the
insertions of recti and oblique muscles in Indian population. Forty eyeballs were
removed from orbit. Insertion of recti and obliqui were cleaned and eyeballs were
perfused with normal saline to regain the volume (hence shape and size) before
recording observations. Insertion of recti and obliqui muscles were observed
under various study parameters. The distance of insertion of recti from the
limbus were found to be 7.3 mm, 8.06 mm, 8.71 mm, and 8.74 mm for medial,
inferior, lateral, and superior rectus, respectively. The superior oblique was
aponeurotic and found to be more variable in mode of insertion as compared to
inferior oblique which had a fleshy and relatively constant insertion. The
observations on insertion of recti and obliqui as obtained in present study
differ from earlier studies to the tune of 1-1.5 mm. This may be attributed to
adoption of method of reperfusion of eyeball before recording observations thus
maintaining size close to in vivo. The observations are expected to be closer to
actual.
PMID- 26417481
TI - Role of cadaveric dissections in modern medical curricula: a study on student
perceptions.
AB - The shift from traditional medical curricula to newer teaching and learning
approaches such as problem-based learning has often resulted in omission or
significant reduction of cadaveric dissections as a method of learning anatomy.
The objective of this study was to evaluate students' perception of dissection in
a graduate-entry, problem-based learning-based medical curriculum. At the end of
the musculoskeletal dissection program in second year, a Likert-type
questionnaire was used to explore medical student perceptions of the perceived
advantages and challenges of cadaveric dissections in comparison with other
anatomy teaching methods. Overall, a majority of students had a positive
perception of dissections. Students who attended dissections regularly had
significantly more positive perceptions about their experience and were in
agreement with statements such as "dissections make learning more interesting"
and "I would be disadvantaged if I did not attend dissection classes." Non
regular attendance was associated with statements about dissections such as "I do
not like the smell," "time consuming," and "bored with the way it is carried
out." A follow-up study after completion of the medical program revealed a
significant improvement of positive perception about dissection. Student
perceptions appear to favour a role for cadaveric dissection in learning anatomy
in modern medical curricula. However, optimal and effective integration of
dissections is important, with consideration given to its structure and extent of
content weighed against logistics and availability of resources; while addressing
negative perceptions of dissection-based teaching.
PMID- 26417482
TI - Bone tumors in pre-modern skulls from human skeletal series of Joseon Dynasty.
AB - To date, there are still very few reports on benign-tumor cases based on East
Asian skeletal series, even though other regions and continents have been well
represented. In our study on the Joseon Human Skeletal Series, we identified
benign bone tumors in two skeletons (cases Nos. 75 and 96). Our radiological
analyses showed both cases to be homogeneous sclerotic bone masses aligned with
the cranial vault suture. In a subsequent series of differential diagnoses, we
determined both cases to be osteoma, the most common bone-tumor type reported for
archaeological samples. Our study is the osteoarchaeological basis for this, the
first-ever report on benign bone neoplasm in a pre-modern East Asian population.
PMID- 26417483
TI - An anomalous portal vein crossing the lesser sac and ending at the upper part of
ductus venosus.
AB - In serial sagittal sections of a fetus on week 9 (crown-rump length, 36 mm), we
incidentally found absence of the usual portal vein through the hepatoduodenal
ligament. Instead, an anomalous portal vein originated behind the pancreatic
body, crossed the lesser sac and merged with the upper part of the ductus
venosus. During the course across the lesser sac, the vein provided a deep notch
of the liver caudate lobe (Spiegel's lobe). The hepatoduodenal ligament contained
the hepatic artery, the common bile duct and, at the right posterior margin of
the ligament, and a branch of the anomalous portal vein which communicated with
the usual right branch of the portal vein at the hepatic hilum. The umbilical
portion of the portal vein took a usual morphology and received the umbilical
vein and gave off the ductus venosus. Although it seemed not to be described yet,
the present anomalous portal vein was likely to be a persistent left vitelline
vein. The hepatoduodenal ligament was unlikely to include the left vitelline vein
in contrast to the usual concept.
PMID- 26417484
TI - Absence of the lateral and third ventricles associated with holoprosencephaly.
AB - We describe a 6-month-old boy suffering from motor and mental retardation. All
radiological features were suggestive of holoprosencephaly with no identifiable
lateral or third ventricles and fusion of the thalami.
PMID- 26417485
TI - Electromyography in musculoskeletal pain: A reappraisal and practical
considerations.
AB - BACKGROUND: Patients with musculoskeletal pain (MSP) and local tenderness in the
back and extremities are frequently referred to electromyography (EMG) laboratory
to assess the integrity of the spinal nerve roots, peripheral nerves, and
skeletal muscles. When focal muscle weakness and anatomical sensory deficits are
clinically evident, this procedure is almost always abnormal. In some situations,
when the presenting symptoms consist of local pain and tenderness without
neuromuscular deficits, its diagnostic utility becomes questionable as
illustrated in the present study. METHODS: EMG findings of 75 patients referred
for evaluation of local MSP and tenderness in the neck and lower back and in the
upper and lower extremities were reviewed. These patients were selected from a
group of 200 patients referred for evaluation of unilateral local pain and
tenderness in various parts of the body. All EMG procedures and clinical
neurologic examination were performed by the author and all underwent magnetic
resonance imaging of the affected parts of the body prior to the procedure. None
of the 75 patients studied had concurrent medical disorders or had previous
spinal root injuries or surgeries to the spine. RESULTS: All 75 patients in this
study showed normal EMG of the affected extremities and normal peripheral nerve
conduction study. Those with herniated disc in the cervical or lumbar spine
presenting with local pain and tenderness in the neck and lower back but without
neurologic deficits or clear radicular symptoms, had normal study also. The
remaining 125 patients excluded from the study, had various EMG and peripheral
nerve abnormalities that can be attributed to concurrent medical disorders and
previous injuries to the spinal roots. CONCLUSIONS: Use of EMG in the diagnosis
of local MSP, unless associated with clinical neurologic deficits, almost always
yields negative results. The utility of this procedure is limited to pathology in
the motor unit. It cannot assess the function of the sensory components of the
spinal roots, small-diameter sensory nerves, and the sensory innervation of the
spine via sinuvertebral nerve. Therefore, if the motor unit is anatomically and
physiologically intact, the procedure is of little value in the diagnosis of MSP.
Likewise, peripheral nerve conduction study is likely to be normal unless clear
neurologic deficits are present. The present study illustrates that a good
history and meticulous neurologic examination should be an integral part of an
ideal electrodiagnostic procedure.
PMID- 26417486
TI - Optical mesoscopy without the scatter: broadband multispectral optoacoustic
mesoscopy.
AB - Optical mesoscopy extends the capabilities of biological visualization beyond the
limited penetration depth achieved by microscopy. However, imaging of opaque
organisms or tissues larger than a few hundred micrometers requires invasive
tissue sectioning or chemical treatment of the specimen for clearing photon
scattering, an invasive process that is regardless limited with depth. We
developed previously unreported broadband optoacoustic mesoscopy as a tomographic
modality to enable imaging of optical contrast through several millimeters of
tissue, without the need for chemical treatment of tissues. We show that the
unique combination of three-dimensional projections over a broad 500 kHz-40 MHz
frequency range combined with multi-wavelength illumination is necessary to
render broadband multispectral optoacoustic mesoscopy (2B-MSOM) superior to
previous optical or optoacoustic mesoscopy implementations.
PMID- 26417487
TI - Optoacoustic detection of tissue glycation.
AB - Oxidative-based diseases including diabetes, chronic renal failure,
cardiovascular diseases and neurological disorders are accompanied by
accumulation of advanced glycation endproducts (AGE). Therefore, AGE-associated
changes in tissue optical properties could yield a viable pathological indicator
for disease diagnostics and monitoring. We investigated whether skin glycation
could be detected based on absorption changes associated with AGE accumulation
using spectral optoacoustic measurements and interrogated the optimal spectral
band for skin glycation determination. Glycated and non-glycated skin was
optoacoustically measured at multiple wavelengths in the visible region. The
detected signals were spectrally processed and compared to measurements of skin
auto-fluorescence and to second harmonic generation multiphoton microscopy
images. Optoacoustic measurements are shown to be capable of detecting skin
glycolysis based on AGE detection. A linear dependence was observed between
optoacoustic intensity and the progression of skin glycation. The findings where
corroborated by autofluorescence observations. Detection sensitivity is enhanced
by observing normalised tissue spectra. This result points to a ratiometric
method for skin glycation detection, specifically at 540 nm and 620 nm. We
demonstrate that optoacoustic spectroscopy could be employed to detect AGE
accumulation, and possibly can be employed as a non-invasive quick method for
monitoring tissue glycation.
PMID- 26417488
TI - Photoacoustic imaging of salivary glands.
AB - In this work, we utilized photoacoustic imaging (PAI) with co-registered
ultrasound (US) to non-invasively assess salivary gland function in vivo. A
significant increase in salivary gland oxygen saturation was observed on PAI
within minutes after gustatory stimulation of healthy mice reflective of the
hyperemic response associated with secretion of saliva. Good correlation was seen
between PAI and Doppler sonography. Salivary adenoid cystic carcinomas showed
higher oxygen saturation compared to surrounding salivary gland tissue. Our
results demonstrate the potential clinical utility of PAI for visualization of
salivary gland physiology and pathology.
PMID- 26417489
TI - In vivo dual-modality photoacoustic and optical coherence tomography imaging of
human dermatological pathologies.
AB - Vascular abnormalities serve as a key indicator for many skin diseases. Currently
available methods in dermatology such as histopathology and dermatoscopy analyze
underlying vasculature in human skin but are either invasive, time-consuming, and
laborious or incapable of providing 3D images. In this work, we applied for the
first time dual-modality photoacoustic and optical coherence tomography that
provides complementary information about tissue morphology and vasculature of
patients with different types of dermatitis. Its noninvasiveness and relatively
short imaging time and the wide range of diseases that it can detect prove the
merits of the dual-modality imaging system and show the great potential of its
clinical use in the future.
PMID- 26417490
TI - Camera array based light field microscopy.
AB - This paper proposes a novel approach for high-resolution light field microscopy
imaging by using a camera array. In this approach, we apply a two-stage relay
system for expanding the aperture plane of the microscope into the size of an
imaging lens array, and utilize a sensor array for acquiring different sub
apertures images formed by corresponding imaging lenses. By combining the
rectified and synchronized images from 5 * 5 viewpoints with our prototype
system, we successfully recovered color light field videos for various fast
moving microscopic specimens with a spatial resolution of 0.79 megapixels at 30
frames per second, corresponding to an unprecedented data throughput of 562.5
MB/s for light field microscopy. We also demonstrated the use of the reported
platform for different applications, including post-capture refocusing, phase
reconstruction, 3D imaging, and optical metrology.
PMID- 26417491
TI - Controlling local temperature in water using femtosecond optical tweezer.
AB - A novel method of directly observing the effect of temperature rise in water at
the vicinity of optical trap center is presented. Our approach relies on changed
values of corner frequency of the optical trap that, in turn, is realized from
its power spectra. Our two color experiment is a unique combination of a non
heating femtosecond trapping laser at 780 nm, coupled to a femtosecond infrared
heating laser at 1560 nm, which precisely controls temperature at focal volume of
the trap center using low powers (100-800 uW) at high repetition rate. The
geometric ray optics model quantitatively supports our experimental data.
PMID- 26417492
TI - Magnetic resonance imaging appropriate for construction of subject-specific head
models for diffuse optical tomography.
AB - Subject-specific head models of which their geometry is based on structural
magnetic resonance images are essential to accurately estimate the spatial
sensitivity profiles for image reconstruction in diffuse optical tomography. T1
weighted magnetic resonance images, which are commonly used for structural
imaging, are not sufficient for the threshold-based segmentation of the
superficial tissues. Two types of pulse sequences, which provide a high contrast
among the superficial tissues, are introduced to complement the segmentation to
construct the subject-specific head models. The magnetic resonance images
acquired by the proposed pulse sequences are robust to the threshold level and
adequate for the threshold-based segmentation of the superficial tissues compared
to the T1- and T2-weighted images. The total scan time of the proposed pulse
sequences is less than one-fourth of that for the T2-weighted pulse sequence.
PMID- 26417493
TI - InstantScope: a low-cost whole slide imaging system with instant focal plane
detection.
AB - We report the development of a high-throughput whole slide imaging (WSI) system
by adapting a cost-effective optomechanical add-on kit to existing microscopes.
Inspired by the phase detection concept in professional photography, we attached
two pinhole-modulated cameras at the eyepiece ports for instant focal plane
detection. By adjusting the positions of the pinholes, we can effectively change
the view angle for the sample, and as such, we can use the translation shift of
the two pinhole-modulated images to identify the optimal focal position. By using
a small pinhole size, the focal-plane-detection range is on the order of
millimeter, orders of magnitude longer than the objective's depth of field. We
also show that, by analyzing the phase correlation of the pinhole-modulated
images, we can determine whether the sample contains one thin section, folded
sections, or multiple layers separated by certain distances - an important piece
of information prior to a detailed z scan. In order to achieve system automation,
we deployed a low-cost programmable robotic arm to perform sample loading and $14
stepper motors to drive the microscope stage to perform x-y scanning. Using a 20X
objective lens, we can acquire a 2 gigapixel image with 14 mm by 8 mm field of
view in 90 seconds. The reported platform may find applications in biomedical
research, telemedicine, and digital pathology. It may also provide new insights
for the development of high-content screening instruments.
PMID- 26417494
TI - Reduction of distortion in photothermal microscopy and its application to the
high-resolution three-dimensional imaging of nonfluorescent tissues.
AB - A scheme for reducing image distortion in photothermal microscopy is presented.
In photothermal microscopy, the signal shape exhibits twin peaks corresponding to
the focusing or defocusing of the probe beam when a sample is scanned in the
axial direction. This causes a distortion when imaging a structured sample in the
axial plane. Here, we demonstrate that image distortion caused by the twin peaks
is effectively suppressed by providing a small offset between two the focal
planes of the pump and the probe beams. Experimental results demonstrate
improvement in resolution, especially in the axial direction, over conventional
optical microscopy-even with the focal offset. When a dry objective lens with a
numerical aperture of 0.95 is used, the full width at half the maximum of the
axial point spread function is 0.6 MUm, which is 50% (62%) smaller than the focal
spot sizes of the pump (probe) beam. Herein, we present high-resolution three
dimensional imaging of thick biological tissues based on the present scheme.
PMID- 26417495
TI - Photoacoustic imaging of cerebral hypoperfusion during acupuncture.
AB - Using acupuncture to treat cerebral hypoperfusion is a hot topic. However, there
is a lack of effective tools to clarify the therapeutic effect of acupuncture on
cerebral hypoperfusion. Here, we show in a mouse model of cerebral hypoperfusion
that photoacoustic tomography (PAT) can noninvasively image cerebral vasculature
and track total hemoglobin (HbT) concentration changes in cerebral hypoperfusion
with acupuncture stimulation on the YangLingQuan (GB34) point. We measured the
changes of HbT concentration and found that the HbT concentration in
hypoperfusion regions was clearly lower than that in the control regions when the
acupuncture was absent; however, it was significantly increased when the
acupuncture was implemented on the GB34 point. We also observed the increase of
vessel size and the generation of new vessels in cerebral hypoperfusion during
acupuncture. Laser speckle imaging (LSI) was employed to validate some of the PAT
findings.
PMID- 26417496
TI - Validation of a partial coherence interferometry method for estimating retinal
shape.
AB - To validate a simple partial coherence interferometry (PCI) based retinal shape
method, estimates of retinal shape were determined in 60 young adults using off
axis PCI, with three stages of modeling using variants of the Le Grand model eye,
and magnetic resonance imaging (MRI). Stage 1 and 2 involved a basic model eye
without and with surface ray deviation, respectively and Stage 3 used model with
individual ocular biometry and ray deviation at surfaces. Considering the
theoretical uncertainty of MRI (12-14%), the results of the study indicate good
agreement between MRI and all three stages of PCI modeling with <4% and <7%
differences in retinal shapes along horizontal and vertical meridians,
respectively. Stage 2 and Stage 3 gave slightly different retinal co-ordinates
than Stage 1 and we recommend the intermediate Stage 2 as providing a simple and
valid method of determining retinal shape from PCI data.
PMID- 26417497
TI - Multimodal fiber source for nonlinear microscopy based on a dissipative soliton
laser.
AB - Recent developments in high energy femtosecond fiber lasers have enabled robust
and lower-cost sources for multiphoton-fluorescence and harmonic-generation
imaging. However, picosecond pulses are better suited for Raman scattering
microscopy, so the ideal multimodal source for nonlinear microcopy needs to
provide both durations. Here we present spectral compression of a high-power
femtosecond fiber laser as a route to producing transform-limited picosecond
pulses. These pulses pump a fiber optical parametric oscillator to yield a robust
fiber source capable of providing the synchronized picosecond pulse trains needed
for Raman scattering microscopy. Thus, this system can be used as a multimodal
platform for nonlinear microscopy techniques.
PMID- 26417498
TI - NIR light propagation in a digital head model for traumatic brain injury (TBI).
AB - Near infrared spectroscopy (NIRS) is capable of detecting and monitoring acute
changes in cerebral blood volume and oxygenation associated with traumatic brain
injury (TBI). Wavelength selection, source-detector separation, optode density,
and detector sensitivity are key design parameters that determine the imaging
depth, chromophore separability, and, ultimately, clinical usefulness of a NIRS
instrument. We present simulation results of NIR light propagation in a digital
head model as it relates to the ability to detect intracranial hematomas and
monitor the peri-hematomal tissue viability. These results inform NIRS instrument
design specific to TBI diagnosis and monitoring.
PMID- 26417499
TI - Novel catheter enabling simultaneous radiofrequency ablation and optical
coherence reflectometry.
AB - A novel radiofrequency ablation catheter has been developed with integrated
custom designed optics, enabling real-time monitoring of radiofrequency ablation
procedures through polarization-sensitive optical coherence reflectometry. The
optics allow for proper tissue illumination through a view-port machined in the
catheter tip, thus providing lesion depth control over the RF ablation treatment.
The system was verified in an in-vitro model of swine myocardium. Optical
performance and thermal stability was confirmed after more than 25 procedures,
without any damage to the optical assembly induced by thermal stress or material
degradation. The use of this catheter in RF ablation treatments may make possible
to assess lesion depth during therapy, thus translating into a reduction of
potential complications on the procedure.
PMID- 26417500
TI - Specific imaging of atherosclerotic plaque lipids with two-wavelength
intravascular photoacoustics.
AB - The lipid content in plaques is an important marker for identifying
atherosclerotic lesions and disease states. Intravascular photoacoustic (IVPA)
imaging can be used to visualize lipids in the artery. In this study, we further
investigated lipid detection in the 1.7-um spectral range. By exploiting the
relative difference between the IVPA signal strengths at 1718 and 1734 nm, we
could successfully detect and differentiate between the plaque lipids and peri
adventitial fat in human coronary arteries ex vivo. Our study demonstrates that
IVPA imaging can positively identify atherosclerotic plaques using only two
wavelengths, which could enable rapid data acquisition in vivo.
PMID- 26417501
TI - Strategy for accurate liver intervention by an optical tracking system.
AB - Image-guided navigation for radiofrequency ablation of liver tumors requires the
accurate guidance of needle insertion into a tumor target. The main challenge of
image-guided navigation for radiofrequency ablation of liver tumors is the
occurrence of liver deformations caused by respiratory motion. This study reports
a strategy of real-time automatic registration to track custom fiducial markers
glued onto the surface of a patient's abdomen to find the respiratory phase, in
which the static preoperative CT is performed. Custom fiducial markers are
designed. Real-time automatic registration method consists of the automatic
localization of custom fiducial markers in the patient and image spaces. The
fiducial registration error is calculated in real time and indicates if the
current respiratory phase corresponds to the phase of the static preoperative CT.
To demonstrate the feasibility of the proposed strategy, a liver simulator is
constructed and two volunteers are involved in the preliminary experiments. An ex
vivo porcine liver model is employed to further verify the strategy for liver
intervention. Experimental results demonstrate that real-time automatic
registration method is rapid, accurate, and feasible for capturing the
respiratory phase from which the static preoperative CT anatomical model is
generated by tracking the movement of the skin-adhered custom fiducial markers.
PMID- 26417502
TI - In vivo imaging of activated microglia in a mouse model of focal cerebral
ischemia by two-photon microscopy.
AB - Microglia are brain resident macrophages rapidly responding to various stimuli to
exert appropriate inflammatory responses. Although they have recently been
exploited as an attractive candidate for imaging neuroinflammation, it is still
difficult to visualize them at the cellular and molecular levels. Here we imaged
activated microglia by establishing intracranial window chamber (ICW) in a mouse
model of focal cerebral ischemia by using two-photon microscopy (TPM), in vivo.
Intravenous injection of fluorescent antibodies allowed us to detect
significantly elevated levels of Iba-1 and CD68 positive activated microglia in
the ipsilateral compared to the contralateral side of the infarct. We further
observed that indomethacin, a non-steroidal anti-inflammatory drug significantly
attenuated CD68-positive microglial activation in ICW, which was further
confirmed by qRT-PCR biochemical analyses. In conclusion, we believe that in vivo
TPM imaging of ICW would be a useful tool to screen for therapeutic interventions
lowering microglial activation hence neuroinflammation.
PMID- 26417503
TI - Observation of sound-induced corneal vibrational modes by optical coherence
tomography.
AB - The mechanical stability of the cornea is critical for maintaining its normal
shape and refractive function. Here, we report an observation of the mechanical
resonance modes of the cornea excited by sound waves and detected by using phase
sensitive optical coherence tomography. The cornea in bovine eye globes exhibited
three resonance modes in a frequency range of 50-400 Hz. The vibration amplitude
of the fundamental mode at 80-120 Hz was ~8 um at a sound pressure level of 100
dB (2 Pa). Vibrography allows the visualization of the radially symmetric
profiles of the resonance modes. A dynamic finite-element analysis supports our
observation.
PMID- 26417504
TI - Non-contact measurement of oxygen saturation with an RGB camera.
AB - A novel method (Sophia) is presented to track oxygen saturation changes in a
controlled environment using an RGB camera placed approximately 1.5 m away from
the subject. The method is evaluated on five healthy volunteers (Fitzpatrick skin
phenotypes II, III, and IV) whose oxygen saturations were varied between 80% and
100% in a purpose-built chamber over 40 minutes each. The method carefully
selects regions of interest (ROI) in the camera image by calculating signal-to
noise ratios for each ROI. This allows it to track changes in oxygen saturation
accurately with respect to a conventional pulse oximeter (median coefficient of
determination, 0.85).
PMID- 26417505
TI - Evaluation of burn severity in vivo in a mouse model using spectroscopic optical
coherence tomography.
AB - Clinical management of burn injuries depends upon an accurate assessment of the
depth of the wound. Current diagnostic methods rely primarily on subjective
visual inspection, which can produce variable results. In this study,
spectroscopic optical coherence tomography was used to objectively evaluate burn
injuries in vivo in a mouse model. Significant spectral differences were observed
and correlated with the depth of the injury as determined by histopathology. The
relevance of these results to clinical burn management in human tissues is
discussed.
PMID- 26417506
TI - Longitudinal far red gene-reporter imaging of cancer metastasis in preclinical
models: a tool for accelerating drug discovery.
AB - In this short communication, we demonstrate for the first time, the use of far
red fluorescent gene reporter, iRFP to longitudinally and non-invasively track
the in vivo process of lymphatic metastases from an orthotopic site of mammary
implantation through lymphatic vessels and to draining lymph nodes. Potentially
useful to accelerate cancer drug discovery as an in vivo screening tool to
monitor the pharmacological arrest of metastasis, we show that the custom as well
as commercial small animal imaging devices have adequate performance to detect
the gene reporter in stably expressing metastatic cancer cells.
PMID- 26417507
TI - Periscope for noninvasive two-photon imaging of murine retina in vivo.
AB - Two-photon microscopy allows visualization of subcellular structures in the
living animal retina. In previously reported experiments it was necessary to
apply a contact lens to each subject. Extending this technology to larger animals
would require fitting a custom contact lens to each animal and cumbersome
placement of the living animal head on microscope stage. Here we demonstrate a
new device, periscope, for coupling light energy into mouse eye and capturing
emitted fluorescence. Using this periscope we obtained images of the RPE and
their subcellular organelles, retinosomes, with larger field of view than
previously reported. This periscope provides an interface with a commercial
microscope, does not require contact lens and its design could be modified to
image retina in larger animals.
PMID- 26417508
TI - Design of high-performance adaptive objective lens with large optical depth
scanning range for ultrabroad near infrared microscopic imaging.
AB - We report on the theory and design of adaptive objective lens for ultra broadband
near infrared light imaging with large dynamic optical depth scanning range by
using an embedded tunable lens, which can find wide applications in deep tissue
biomedical imaging systems, such as confocal microscope, optical coherence
tomography (OCT), two-photon microscopy, etc., both in vivo and ex vivo. This
design is based on, but not limited to, a home-made prototype of liquid-filled
membrane lens with a clear aperture of 8mm and the thickness of 2.55mm ~3.18mm.
It is beneficial to have an adaptive objective lens which allows an extended
depth scanning range larger than the focal length zoom range, since this will
keep the magnification of the whole system, numerical aperture (NA), field of
view (FOV), and resolution more consistent. To achieve this goal, a systematic
theory is presented, for the first time to our acknowledgment, by inserting the
varifocal lens in between a front and a back solid lens group. The designed
objective has a compact size (10mm-diameter and 15mm-length), ultrabroad working
bandwidth (760nm - 920nm), a large depth scanning range (7.36mm in air) - 1.533
times of focal length zoom range (4.8mm in air), and a FOV around 1mm * 1mm.
Diffraction-limited performance can be achieved within this ultrabroad bandwidth
through all the scanning depth (the resolution is 2.22 MUm - 2.81 MUm, calculated
at the wavelength of 800nm with the NA of 0.214 - 0.171). The chromatic focal
shift value is within the depth of focus (field). The chromatic difference in
distortion is nearly zero and the maximum distortion is less than 0.05%.
PMID- 26417509
TI - Modal content of living human cone photoreceptors.
AB - Decades of experimental and theoretical investigations have established that
photoreceptors capture light based on the principles of optical waveguiding. Yet
considerable uncertainty remains, even for the most basic prediction as to
whether photoreceptors support more than a single waveguide mode. To test for
modal behavior in human cone photoreceptors in the near infrared, we took
advantage of adaptive-optics optical coherence tomography (AO-OCT, lambdac = 785
nm) to noninvasively image in three dimensions the reflectance profile of cones.
Modal content of reflections generated at the cone inner segment and outer
segment junction (IS/OS) and cone outer segment tip (COST) was examined over a
range of cone diameters in 1,802 cones from 0.6 degrees to 10 degrees retinal
eccentricity. Second moment analysis in conjunction with theoretical predictions
indicate cone IS and OS have optical properties consistent of waveguides, which
depend on segment diameter and refractive index. Cone IS was found to support a
single mode near the fovea (<=3 degrees ) and multiple modes further away (>4
degrees ). In contrast, no evidence of multiple modes was found in the cone OSs.
The IS/OS and COST reflections share a common optical aperture, are most circular
near the fovea, show no orientation preference, and are temporally stable. We
tested mode predictions of a conventional step-index fiber model and found that
in order to fit our AO-OCT results required a lower estimate of the IS refractive
index and introduction of an IS focusing/tapering effect.
PMID- 26417510
TI - Pupil tracking optical coherence tomography for precise control of pupil entry
position.
AB - To maximize the collection efficiency of back-scattered light, and to minimize
aberrations and vignetting, the lateral position of the scan pivot of an optical
coherence tomography (OCT) retinal scanner should be imaged to the center of the
ocular pupil. Additionally, several retinal structures including Henle's Fiber
Layer (HFL) exhibit reflectivities that depend on illumination angle, which can
be controlled by varying the pupil entry position of the OCT beam. In this work,
we describe an automated method for controlling the lateral pupil entry position
in retinal OCT by utilizing pupil tracking in conjunction with a 2D fast steering
mirror placed conjugate to the retinal plane. We demonstrate that pupil tracking
prevents lateral motion artifacts from impeding desired pupil entry locations,
and enables precise pupil entry positioning and therefore control of the
illumination angle of incidence at the retinal plane. We use our prototype pupil
tracking OCT system to directly visualize the obliquely oriented HFL.
PMID- 26417511
TI - Algorithm for mapping cutaneous tissue oxygen concentration using hyperspectral
imaging.
AB - The measurement of tissue oxygenation plays an important role in the diagnosis
and therapeutic assessment of a large variety of diseases. Many different methods
have been developed and are currently applied in clinical practice for the
measurement of tissue oxygenation. Unfortunately, each of these methods has its
own limitations. In this paper we proposed the use of hyperspectral imaging as
new method for the assessment of the tissue oxygenation level. To extract this
information from hyperspectral images a new algorithm for mapping cutaneous
tissue oxygen concentration was developed. This algorithm takes into account and
solves some problems related to setting and calculation of some parameters
derived from hyperspectral images. The algorithm was tested with good results on
synthetic images and then validated on the fingers of a hand with different blood
irrigation states. The results obtained have proved the ability of hyperspectral
imaging together with the developed algorithm to map the oxy- and deoxyhemoglobin
distribution on the analyzed fingers. These are only preliminary results and
other studies should be done before this approach to be used in the clinical
setting for the diagnosis and monitoring of various diseases.
PMID- 26417513
TI - Optical imaging of the prefrontal activity in joint attention experience.
AB - Functional near-infrared spectroscopy (fNIRS) was used to measure the prefrontal
activity in joint attention experience. 16 healthy adults participated in the
experiment in which 42 optical channels were fixed over the anterior prefrontal
cortex (aPFC), dorsolateral prefrontal cortex (DLPFC), inferior frontal gyrus
(IFG) and a small anterior portion of the superior temporal gyrus (STG). Video
stimuli were used to engender joint or non-joint attention experience in
observers. Cortical hemodynamic response and functional connectivity were
measured and averaged across all subjects for each stimulus condition. Our data
showed the activation in joint attention located in the aPFC and DLPFC
bilaterally, but dominantly in the left hemisphere. This observation, together
with the previous findings on infants and children, provides a clear
developmental scenario on the prefrontal activation associated with joint
attention process. In the case of non-joint attention condition, only a small
region of the right DLPFC was activated. Functional connectivity was observed to
be enhanced, but differently in joint and non-joint attention condition.
PMID- 26417512
TI - Bedside monitoring of patients with shock using a portable spatially-resolved
near-infrared spectroscopy.
AB - Clinical monitoring of shock mainly depends on blood-oxygen-indices obtained from
invasive blood sample tests. The central internal jugular central vein
oxygenation level (ScvO2) has been considered as a gold standard indicator for
shock prediction. We developed a noninvasive spatially-resolved near-infrared
spectroscopy (SR-NIRS) to measure tissue blood oxygen saturation (StO2)
surrounding the region of taking blood sample for the ScvO2 test in 25 patients
with shock. StO2 values were found to be highly correlated (r = 0.84, p < 0.001)
with ScvO2 levels and the concordance coefficient of 0.80 is high. The results
suggest the potential of noninvasive SR-NIRS for bedside shock monitoring.
PMID- 26417514
TI - Rapid spontaneous Raman light sheet microscopy using cw-lasers and tunable
filters.
AB - We perform rapid spontaneous Raman 2D imaging in light-sheet microscopy using
continuous wave lasers and interferometric tunable filters. By angularly tuning
the filter, the cut-on/off edge transitions are scanned along the excited Stokes
wavelengths. This allows obtaining cumulative intensity profiles of the scanned
vibrational bands, which are recorded on image stacks; resembling a spectral
version of the knife-edge technique to measure intensity profiles. A further
differentiation of the stack retrieves the Raman spectra at each pixel of the
image which inherits the 3D resolution of the host light sheet system. We
demonstrate this technique using solvent solutions and composites of polystyrene
beads and lipid droplets immersed in agar and by imaging the C-H (2800-3100cm(
1)) region in a C. elegans worm. The image acquisition time results in 4 orders
of magnitude faster than confocal point scanning Raman systems, allowing the
possibility of performing fast spontaneous Raman.3D-imaging on biological
samples.
PMID- 26417515
TI - In vivo microscopy of hemozoin: towards a needle free diagnostic for malaria.
AB - Clinical diagnosis of malaria suffers from poor specificity leading to
overtreatment with antimalarial medications. Alternatives, like blood smear
microscopy or antigen-based tests, require a blood sample. We investigate in vivo
microscopy as a needle-free malaria diagnostic. Two optical signatures,
birefringence and absorbance, of the endogenous malaria by-product hemozoin were
evaluated as in vivo optical biomarkers. Hemozoin birefringence was difficult to
detect in highly scattering tissue; however, hemozoin absorbance was observed in
increasingly complex biological environments and detectable over a clinically
relevant range of parasitemia in vivo in a P. yoelii-infected mouse model of
malaria.
PMID- 26417516
TI - Ultrastructural features of collagen in thyroid carcinoma tissue observed by
polarization second harmonic generation microscopy.
AB - Changes in collagen ultrastructure between malignant and normal human thyroid
tissue were investigated ex vivo using polarization second harmonic generation
(SHG) microscopy. The second-order nonlinear optical susceptibility tensor
component ratio and the degree of linear polarization (DOLP) of the SHG signal
were measured. The ratio values are related to the collagen ultrastructure, while
DOLP indicates the relative amount of coherent signal and incoherent scattering
of SHG. Increase in ratio values and decrease in DOLP were observed for tumor
tissue compared to normal thyroid, indicating higher ultrastructural disorder in
tumor collagen.
PMID- 26417517
TI - Diverse effects of a 445 nm diode laser on isometric contraction of the rat
aorta.
AB - The usefulness of visible lasers in treating vascular diseases is controversial.
It is probable that multiple effects of visible lasers on blood vessels and their
unclear mechanisms have hampered the usefulness of this therapy. Therefore,
elucidating the precise actions and mechanisms of the effects of lasers on blood
vessels would provide insight into potential biomedical applications. Here, using
organ chamber isometric contraction measurements, western blotting, patch-clamp,
and en face immunohistochemistry, we showed that a 445 nm diode laser contracted
rat aortic rings, both by activating endothelial nitric oxide synthase and by
increasing oxidative stress. In addition to the effects on the endothelium, the
laser also directly relaxed and contracted vascular smooth muscle by inhibiting L
type Ca(2+) channels and by activating protein tyrosine kinases, respectively.
Thus, we conclude that exposure to 445 nm laser might contract and dilate blood
vessels in the endothelium and smooth muscle via distinct mechanisms.
PMID- 26417518
TI - Label-free surface-enhanced Raman spectroscopy for detection of colorectal cancer
and precursor lesions using blood plasma.
AB - Fecal based tests have limited diagnostic values in detecting adenomatous polyps,
the precursor lesions to colorectal cancer (CRC). Surface enhanced Raman
spectroscopy (SERS) using silver nanoparticles as substrate is a multiplexed
analytical technique capable of detecting biomolecules with high sensitivity.
This study utilizes SERS to analyze blood plasma for detecting both CRC and
adenomatous polyps for the first time. Blood plasma samples are collected from
healthy control subjects and patients diagnosed with adenomas and CRC. Using a
real-time Raman system, SERS spectra for blood plasma samples are measured in 1
s. The collected SERS spectra are analyzed with partial least squares
discriminant analysis. Classification of normal versus CRC plus adenomatous
polyps achieved diagnostic sensitivity of 86.4% and specificity of 80%. The
results suggest that blood plasma SERS analysis could be a potential screening
test to detect both CRC and adenomas.
PMID- 26417519
TI - Using functional near-infrared spectroscopy (fNIRS) to detect the prefrontal
cortical responses to deception under different motivations.
AB - In this study, functional near-infrared spectroscopy (fNIRS) was adopted to
investigate the prefrontal cortical responses to deception under different
motivations. By using a feigned memory impairment paradigm, 19 healthy adults
were asked to deceive under the two different motivations: to obtain rewards and
to avoid punishments. Results indicated that when deceiving for obtaining
rewards, there was greater neural activation in the right inferior frontal gyrus
(IFG) than the control condition. When deceiving for avoiding punishments, there
was greater activation in the right inferior frontal gyrus (IFG) and the left
middle frontal gyrus (MFG) than the control condition. In addition, deceiving for
avoiding punishments led to greater neural activation in the left MFG than when
deceiving for obtaining rewards. Furthermore, the results showed a moderate hit
rate in detecting deception under either motivation. These results demonstrated
that deception with different motivations led to distinct responses in the
prefrontal cortex. fNIRS could provide a useful technique for the detection of
deception with strategy of feigning memory impairment under different
motivations.
PMID- 26417520
TI - Three-dimensional, three-vector-component velocimetry of cilia-driven fluid flow
using correlation-based approaches in optical coherence tomography.
AB - Microscale quantification of cilia-driven fluid flow is an emerging area in
medical physiology, including pulmonary and central nervous system physiology.
Cilia-driven fluid flow is most completely described by a three-dimensional,
three-component (3D3C) vector field. Here, we generate 3D3C velocimetry
measurements by synthesizing higher dimensional data from lower dimensional
measurements obtained using two separate optical coherence tomography (OCT)-based
approaches: digital particle image velocimetry (DPIV) and dynamic light
scattering (DLS)-OCT. Building on previous work, we first demonstrate directional
DLS-OCT for 1D2C velocimetry measurements in the sub-1 mm/s regime (sub-2.5
inch/minute regime) of cilia-driven fluid flow in Xenopus epithelium, an
important animal model of the ciliated respiratory tract. We then extend our
analysis toward 3D3C measurements in Xenopus using both DLS-OCT and DPIV. We
demonstrate the use of DPIV-based approaches towards flow imaging of Xenopus
cerebrospinal fluid and mouse trachea, two other important ciliary systems. Both
of these flows typically fall in the sub-100 MUm/s regime (sub-0.25 inch/minute
regime). Lastly, we develop a framework for optimizing the signal-to-noise ratio
of 3D3C flow velocity measurements synthesized from 2D2C measures in non
orthogonal planes. In all, 3D3C OCT-based velocimetry has the potential to
comprehensively characterize the flow performance of biological ciliated
surfaces.
PMID- 26417521
TI - Signal enhancement in multiphoton imaging by the use of coated glass substrates.
AB - In nonlinear optical imaging of biological specimens, more than half of the
generated luminescence signal is lost, when signal collection is performed in the
epi-illuminated geometry. In this study, we enhanced the collected luminescence
signal by the use of alternating multiply-coated layers of tantalum pentoxide
(Ta2O5) and silicon dioxide (SiO2) on standard microscope cover glasses that has
high transmission in the near-infrared wavelength region and high reflection of
the visible, luminescence signal. Our coating is biocompatible, allows visual
examination of the specimens and optimize collection of the luminescence signal.
We demonstrated this approach on a number of specimens including sulforhodamine
solution, fluorescence microspheres, and labeled 3T3 cells. In all cases, the use
of coated cover glass enhanced signal, optimally by a factor of about 2. Image
analysis of labeled 3T3 cells also shows signal enhancement did not contribute to
additional photobleaching. Our results show that properly designed coated cover
glass can enhance detected signal in multiphoton microscopy and result in
improved image quality.
PMID- 26417522
TI - Quantitative imaging of light-triggered doxorubicin release.
AB - The efficacy of chemotherapy is related, in large part, to the concentration of
drug that reaches tumor sites. Doxorubicin (DOX) is a common anti-cancer drug
that is also approved for use in liposomal form for the treatment of ovarian
cancer. We recently developed a porphyrin-phospholipid (PoP)-liposome system that
enables on demand release of DOX from liposomes using near infrared irradiation
to improve DOX bioavailability. Owing to its intrinsic fluorescence, it is
possible, and desirable, to quantify DOX concentration and distribution,
preferably noninvasively. Here we quantified DOX distribution following light
triggered drug release in phantoms and an animal carcass using spatial frequency
domain imaging. This study demonstrates the feasibility of non-invasive
quantitative mapping of DOX distributions in target areas.
PMID- 26417523
TI - Quantitative analysis of platelets aggregates in 3D by digital holographic
microscopy.
AB - Platelet spreading and retraction play a pivotal role in the platelet plugging
and the thrombus formation. In routine laboratory, platelet function tests
include exhaustive information about the role of the different receptors present
at the platelet surface without information on the 3D structure of platelet
aggregates. In this work, we develop, a method in Digital Holographic Microscopy
(DHM) to characterize the platelet and aggregate 3D shapes using the quantitative
phase contrast imaging. This novel method is suited to the study of platelets
physiology in clinical practice as well as the development of new drugs.
PMID- 26417524
TI - Automated choroidal neovascularization detection algorithm for optical coherence
tomography angiography.
AB - Optical coherence tomography angiography has recently been used to visualize
choroidal neovascularization (CNV) in participants with age-related macular
degeneration. Identification and quantification of CNV area is important
clinically for disease assessment. An automated algorithm for CNV area detection
is presented in this article. It relies on denoising and a saliency detection
model to overcome issues such as projection artifacts and the heterogeneity of
CNV. Qualitative and quantitative evaluations were performed on scans of 7
participants. Results from the algorithm agreed well with manual delineation of
CNV area.
PMID- 26417525
TI - Contrast-based sensorless adaptive optics for retinal imaging.
AB - Conventional adaptive optics ophthalmoscopes use wavefront sensing methods to
characterize ocular aberrations for real-time correction. However, there are
important situations in which the wavefront sensing step is susceptible to
difficulties that affect the accuracy of the correction. To circumvent these,
wavefront sensorless adaptive optics (or non-wavefront sensing AO; NS-AO) imaging
has recently been developed and has been applied to point-scanning based retinal
imaging modalities. In this study we show, for the first time, contrast-based NS
AO ophthalmoscopy for full-frame in vivo imaging of human and animal eyes. We
suggest a robust image quality metric that could be used for any imaging
modality, and test its performance against other metrics using (physical) model
eyes.
PMID- 26417527
TI - Fast time-lens-based line-scan single-pixel camera with multi-wavelength source.
AB - A fast time-lens-based line-scan single-pixel camera with multi-wavelength source
is proposed and experimentally demonstrated in this paper. A multi-wavelength
laser instead of a mode-locked laser is used as the optical source. With a
diffraction grating and dispersion compensating fibers, the spatial information
of an object is converted into temporal waveforms which are then randomly
encoded, temporally compressed and captured by a single-pixel photodetector. Two
algorithms (the dictionary learning algorithm and the discrete cosine transform
based algorithm) for image reconstruction are employed, respectively. Results
show that the dictionary learning algorithm has greater capability to reduce the
number of compressive measurements than the DCT-based algorithm. The effective
imaging frame rate increases from 200 kHz to 1 MHz, which shows a significant
improvement in imaging speed over conventional single-pixel cameras.
PMID- 26417526
TI - Fast single photon avalanche photodiode-based time-resolved diffuse optical
tomography scanner.
AB - Resolution in diffuse optical tomography (DOT) is a persistent problem and is
primarily limited by high degree of light scatter in biological tissue. We showed
previously that the reduction in photon scatter between a source and detector
pair at early time points following a laser pulse in time-resolved DOT is highly
dependent on the temporal response of the instrument. To this end, we developed a
new single-photon avalanche photodiode (SPAD) based time-resolved DOT scanner.
This instrument uses an array of fast SPADs, a femto-second Titanium Sapphire
laser and single photon counting electronics. In combination, the overall
instrument temporal impulse response function width was 59 ps. In this paper, we
report the design of this instrument and validate its operation in symmetrical
and irregularly shaped optical phantoms of approximately small animal size. We
were able to accurately reconstruct the size and position of up to 4 absorbing
inclusions, with increasing image quality at earlier time windows. We attribute
these results primarily to the rapid response time of our instrument. These data
illustrate the potential utility of fast SPAD detectors in time-resolved DOT.
PMID- 26417528
TI - Direct regularization from co-registered anatomical images for MRI-guided near
infrared spectral tomographic image reconstruction.
AB - Combining anatomical information from high resolution imaging modalities to guide
near-infrared spectral tomography (NIRST) is an efficient strategy for improving
the quality of the reconstructed spectral images. A new approach for
incorporating image information directly into the inversion matrix regularization
was examined using Direct Regularization from Images (DRI), which encodes the
gray-scale data into the NIRST image reconstruction problem. This process has the
benefit of eliminating user intervention such as image segmentation of distinct
regions. Specifically, the Dynamic Contrast Enhanced Magnetic Resonance (DCE-MR)
image intensity value differences within the anatomical image were used to
implement an exponentially-weighted regularization function between the image
pixels. The algorithm was validated using simulated reconstructions with noise,
and the results showed that spatial resolution and robustness of the
reconstructed images were significantly improved by appropriate choice of the
regularization weight parameters. The proposed approach was also tested on in
vivo breast data acquired in a recent clinical trial combining NIRST / MRI for
cancer tumor characterization. Relative to the standard "no priors" diffuse
recovery, the contrast of the tumor to the normal surrounding tissue increased
from 2.4 to 3.6, and the difference between the tumor size segmented from DCE-MR
images and reconstructed optical images decreased from 18% to 6%, while there was
an overall decrease in surface artifacts.
PMID- 26417529
TI - Pump-probe imaging of pigmented cutaneous melanoma primary lesions gives insight
into metastatic potential.
AB - Metastatic melanoma is associated with a poor prognosis, but no method reliably
predicts which melanomas of a given stage will ultimately metastasize and which
will not. While sentinel lymph node biopsy (SLNB) has emerged as the most
powerful predictor of metastatic disease, the majority of people dying from
metastatic melanoma still have a negative SLNB. Here we analyze pump-probe
microscopy images of thin biopsy slides of primary melanomas to assess their
metastatic potential. Pump-probe microscopy reveals detailed chemical information
of melanin with subcellular spatial resolution. Quantification of the molecular
signatures without reference standards is achieved using a geometrical
representation of principal component analysis. Melanin structure is analyzed in
unison with the chemical information by applying principles of mathematical
morphology. Results show that melanin in metastatic primary lesions has lower
chemical diversity than non-metastatic primary lesions, and contains two distinct
phenotypes that are indicative of aggressive disease. Further, the mathematical
morphology analysis reveals melanin in metastatic primary lesions has a distinct
"dusty" quality. Finally, a statistical analysis shows that the combination of
the chemical information with spatial structures predicts metastatic potential
with much better sensitivity than SLNB and high specificity, suggesting pump
probe microscopy can be an important tool to help predict the metastatic
potential of melanomas.
PMID- 26417530
TI - Intrinsic heating in optically trapped Au nanoparticles measured by dark-field
spectroscopy.
AB - Assessing the degree of heating present when a metal nanoparticle is trapped in
an optical tweezers is critical for its appropriate use in biological
applications as a nanoscale force sensor. Heating is necessarily present for
trapped plasmonic particles because of the non-negligible extinction which
contributes to an enhanced polarisability. We present a robust method for
characterising the degree of heating of trapped metallic nanoparticles, using the
intrinsic temperature dependence of the localised surface plasmon resonance
(LSPR) to infer the temperature of the surrounding fluid at different incident
laser powers. These particle specific measurements can be used to infer the rate
of heating and local temperature of trapped nanoparticles. Our measurements
suggest a considerable amount of a variability in the degree of heating, on the
range of 414-673 K/W, for different 100 nm diameter Au nanoparticles, and we
associated this with variations in the axial trapping position.
PMID- 26417532
TI - CORRIGENDUM.
AB - [This corrects the article on p. 13 in vol. 10, PMID: 25709858.].
PMID- 26417531
TI - Master slave en-face OCT/SLO.
AB - Master Slave optical coherence tomography (MS-OCT) is an OCT method that does not
require resampling of data and can be used to deliver en-face images from several
depths simultaneously. As the MS-OCT method requires important computational
resources, the number of multiple depth en-face images that can be produced in
real-time is limited. Here, we demonstrate progress in taking advantage of the
parallel processing feature of the MS-OCT technology. Harnessing the capabilities
of graphics processing units (GPU)s, information from 384 depth positions is
acquired in one raster with real time display of up to 40 en-face OCT images.
These exhibit comparable resolution and sensitivity to the images produced using
the conventional Fourier domain based method. The GPU facilitates versatile real
time selection of parameters, such as the depth positions of the 40 images out of
the set of 384 depth locations, as well as their axial resolution. In each
updated displayed frame, in parallel with the 40 en-face OCT images, a scanning
laser ophthalmoscopy (SLO) lookalike image is presented together with two B-scan
OCT images oriented along rectangular directions. The thickness of the SLO
lookalike image is dynamically determined by the choice of number of en-face OCT
images displayed in the frame and the choice of differential axial distance
between them.
PMID- 26417534
TI - The effect of multiple micronutrient supplementation on quality of life in
patients with symptomatic heart failure secondary to ischemic heart disease: a
prospective case series clinical study.
AB - Heart failure is a progressive cardiovascular disorder and, in most cases, begins
with atherosclerosis and ischemic heart disease. The prognosis of patients with
heart failure is poor, even with improvement on the management of all forms of
ischemic heart disease. There have been studies on heart failure using a single
nutrient or a combination of multiple nutrients. Results are mixed. The aim of
this study was to assess the influence of multiple micronutrient supplementation
using the quality of life measure on patients with heart failure secondary to
ischemic heart disease. This prospective case series followed 12 patients for a
period between 3 to 8 months, using the Minnesota Living with Heart Failure
Questionnaire (MLHFQ) as the sole outcome measure. The primary outcome was a
score change over time between the start and endpoint of treatment. Change in
MLHFQ mean total score was 27.08 +/- 20.43 and mean symptoms score was 4.67 +/-
3.34. Paired t-test showed a difference between baseline and endpoint of
treatment (P < 0.001), which was statistically significant. A high dose of
multiple micronutrients may have beneficial effects on cardiac function in
patients with symptomatic heart failure. This study indicates the need for long
term controlled studies to test the efficacy and safety of this economic approach
in managing heart failure.
PMID- 26417533
TI - Proteomic approaches to identify circulating biomarkers in patients with
abdominal aortic aneurysm.
AB - Abdominal aortic aneurysm (AAA) is a common condition with high mortality when
ruptured. Most clinicians agree that small AAAs are best managed by
ultrasonographic surveillance. However, it has been stated in recent reviews that
a serum/plasma biomarker that predicts AAA rupture risk would be a powerful tool
in stratifying patients with small AAAs. Identification of such circulating
biomarkers with traditional hypothesis driven studies has been unsuccessful. In
this review we summarize six studies using different proteomic approaches to find
new, potential plasma AAA biomarker candidates. In conclusion, by using proteomic
approaches novel potential plasma biomarkers for AAA have been identified.
PMID- 26417535
TI - Early Illustrations of Geste Antagoniste in Cervical and Generalized Dystonia.
AB - BACKGROUND: Geste antagoniste, or sensory trick, is a voluntary maneuver that
temporarily reduces the severity of dystonic postures or movements. We present a
historical review of early reports and illustrations of geste antagoniste.
RESULTS: In 1894, Brissaud described this phenomenon in Paris in patients with
torticollis. He noted that a violent muscular contraction could be reversed by a
minor voluntary action. He considered the improvement obtained by what he called
"simple mannerisms, childish behaviour or fake pathological movements" was proof
of the psychogenic origin of what he named mental torticollis. This concept was
supported by photographical illustrations of the patients. The term geste
antagoniste was used by Brissaud's pupils, Meige and Feindel, in their 1902
monograph on movement disorders. Other reports and illustrations of this sign
were published in Europe between 1894 and 1906. Although not mentioned
explicitly, geste antagoniste was also illustrated in a case report of
generalized dystonia in Oppenheim's 1911 seminal description of dystonia
musculorum deformans in Berlin. DISCUSSION: Brissaud-Meige's misinterpretation of
the geste antagoniste unfortunately anchored the psychogenic origin of dystonia
for decades. In New York, Herz brought dystonia back into the realm of organic
neurology in 1944. Thereafter, it was given prominence by other authors, notably
Fahn and Marsden in the 1970-1980s. Nowadays, neurologists routinely investigate
for geste antagoniste when a dystonic syndrome is suspected, because it provides
a further argument in favor of dystonia. The term alleviating maneuver was
proposed in 2014 to replace sensory trick or geste antagoniste. This major sign
is now part of the motor phenomenology of the 2013 Movement Disorder Society's
classification of dystonia.
PMID- 26417537
TI - Erratum for Vinuela A, Kang UJ. Reversibility of tardive dyskinesia syndrome.
Tremor Other Hyperkinet Mov. 2014; 4. doi: 10.7916/D86Q1VXZ.
PMID- 26417536
TI - Intermediate Phenotypes of ATP1A3 Mutations: Phenotype-Genotype Correlations.
AB - BACKGROUND: ATP1A3-related disorders include rapid-onset dystonia-parkinsonism
(RDP or DYT12), alternating hemiplegia of childhood (AHC), and CAPOS syndrome
(Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural
hearing loss). CASE REPORT: We report two cases with intermediate forms between
RDP and AHC. Patient 1 initially presented with the AHC phenotype, but the RDP
phenotype emerged at age 14 years. The second patient presented with levodopa
responsive paroxysmal oculogyria, a finding never before reported in ATP1A3
related disorders. Genetic testing confirmed heterozygous changes in the ATP1A3
gene in both patients, one of them novel. DISCUSSION: Intermediate phenotypes of
RDP and AHC support the concept that these two disorders are part of a spectrum.
We add our cases to the phenotype-genotype correlations of ATP1A3-related
disorders.
PMID- 26417539
TI - Demographics and density estimates of two three-toed box turtle (Terrapene
carolina triunguis) populations within forest and restored prairie sites in
central Missouri.
AB - Box turtles (Terrapene carolina) are widely distributed but vulnerable to
population decline across their range. Using distance sampling, morphometric
data, and an index of carapace damage, we surveyed three-toed box turtles
(Terrapene carolina triunguis) at 2 sites in central Missouri, and compared
differences in detection probabilities when transects were walked by one or two
observers. Our estimated turtle densities within forested cover was less at the
Thomas S. Baskett Wildlife Research and Education Center, a site dominated by
eastern hardwood forest (d = 1.85 turtles/ha, 95% CI [1.13, 3.03]) than at the
Prairie Fork Conservation Area, a site containing a mix of open field and
hardwood forest (d = 4.14 turtles/ha, 95% CI [1.99, 8.62]). Turtles at Baskett
were significantly older and larger than turtles at Prairie Fork. Damage to the
carapace did not differ significantly between the 2 populations despite the more
prevalent habitat management including mowing and prescribed fire at Prairie
Fork. We achieved improved estimates of density using two rather than one
observer at Prairie Fork, but negligible differences in density estimates between
the two methods at Baskett. Error associated with probability of detection
decreased at both sites with the addition of a second observer. We provide
demographic data on three-toed box turtles that suggest the use of a range of
habitat conditions by three-toed box turtles. This case study suggests that
habitat management practices and their impacts on habitat composition may be a
cause of the differences observed in our focal populations of turtles.
PMID- 26417538
TI - Novel epitopes identified from efflux pumps of Mycobacterium tuberculosis could
induce cytotoxic T lymphocyte response.
AB - Overcoming drug-resistance is one of the major challenges to control tuberculosis
(TB). The up-regulation of efflux pumps is one common mechanism that leads to
drug-resistance. Therefore, immunotherapy targeting these efflux pump antigens
could be promising strategy to be combined with current chemotherapy. Considering
that CD8+ cytotoxic T lymphocytes (CTLs) induced by antigenic peptides (epitopes)
could elicit HLA-restricted anti-TB immune response, efflux pumps from classical
ABC family (Mycobacterium tuberculosis, Mtb) were chosen as target antigens to
identify CTL epitopes. HLA-A2 restricted candidate peptides from Rv2937, Rv2686c
and Rv2687c of Mycobacterium tuberculosis were predicted, synthesized and tested.
Five peptides could induce IFN-gamma release and cytotoxic activity in PBMCs from
HLA-A2(+) PPD(+) donors. Results from HLA-A2/K(b) transgenic mice immunization
assay suggested that four peptides Rv2937-p168, Rv2937-p266, Rv2686c-p151, and
Rv2686c-p181 could induce significant CTL response in vivo. These results
suggested that these novel epitopes could be used as immunotherapy candidates to
TB drug-resistance.
PMID- 26417540
TI - Temporal and spatial strategies in an active place avoidance task on Carousel: a
study of effects of stability of arena rotation speed in rats.
AB - The active place avoidance task is a dry-arena task used to assess spatial
navigation and memory in rodents. In this task, a subject is put on a rotating
circular arena and avoids an invisible sector that is stable in relation to the
room. Rotation of the arena means that the subject's avoidance must be active,
otherwise the subject will be moved in the to-be-avoided sector by the rotation
of the arena and a slight electric shock will be administered. The present
experiment explored the effect of variable arena rotation speed on the ability to
avoid the to-be-avoided sector. Subjects in a group with variable arena rotation
speed learned to avoid the sector with the same speed and attained the same
avoidance ability as rats in a group with a stable arena rotation speed. Only a
slight difference in preferred position within the room was found between the two
groups. No difference was found between the two groups in the dark phase, where
subjects could not use orientation cues in the room. Only one rat was able to
learn the avoidance of the to-be-avoided sector in this phase. The results of the
experiment suggest that idiothetic orientation and interval timing are not
crucial for learning avoidance of the to-be-avoided sector. However, idiothetic
orientation might be sufficient for avoiding the sector in the dark.
PMID- 26417541
TI - Humans differ in their personal microbial cloud.
AB - Dispersal of microbes between humans and the built environment can occur through
direct contact with surfaces or through airborne release; the latter mechanism
remains poorly understood. Humans emit upwards of 10(6) biological particles per
hour, and have long been known to transmit pathogens to other individuals and to
indoor surfaces. However it has not previously been demonstrated that humans emit
a detectible microbial cloud into surrounding indoor air, nor whether such clouds
are sufficiently differentiated to allow the identification of individual
occupants. We used high-throughput sequencing of 16S rRNA genes to characterize
the airborne bacterial contribution of a single person sitting in a sanitized
custom experimental climate chamber. We compared that to air sampled in an
adjacent, identical, unoccupied chamber, as well as to supply and exhaust air
sources. Additionally, we assessed microbial communities in settled particles
surrounding each occupant, to investigate the potential long-term fate of
airborne microbial emissions. Most occupants could be clearly detected by their
airborne bacterial emissions, as well as their contribution to settled particles,
within 1.5-4 h. Bacterial clouds from the occupants were statistically distinct,
allowing the identification of some individual occupants. Our results confirm
that an occupied space is microbially distinct from an unoccupied one, and
demonstrate for the first time that individuals release their own personalized
microbial cloud.
PMID- 26417544
TI - Insight on the anatomy, systematic relationships, and age of the Early Cretaceous
ankylopollexian dinosaur Dakotadon lakotaensis.
AB - Knowledge regarding the early evolution within the dinosaurian clade
Ankylopollexia drastically increased over the past two decades, in part because
of an increase in described taxa from the Early Cretaceous of North America.
These advances motivated the recent completion of extensive preparation and
conservation work on the holotype and only known specimen of Dakotadon
lakotaensis, a basal ankylopollexian from the Lakota Formation of South Dakota.
That specimen (SDSM 8656) preserves a partial skull, lower jaws, a single dorsal
vertebra, and two caudal vertebrae. That new preparation work exposed several
bones not included in the original description and revealed that other bones were
previously misidentified. The presence of extensive deformation in areas of the
skull is also noted that influenced inaccuracies in prior descriptions and
reconstructions of this taxon. In addition to providing an extensive re
description of D. lakotaensis, this study reviews previously proposed diagnoses
for this taxon, identifies two autapomorphies, and provides an extensive
differential diagnosis. Dakotadon lakotaensis is distinct from the only other
ankylopollexian taxon known from the Lakota Formation, Osmakasaurus depressus, in
the presence of two prominent, anteroposteriorly oriented ridges on the ventral
surfaces of the caudal vertebrae, the only overlapping material preserved between
these taxa. The systematic relationships of D. lakotaensis are evaluated using
both the parsimony and posterior probability optimality criteria, with both sets
of analyses recovering D. lakotaensis as a non-hadrosauriform ankylopollexian
that is more closely related to taxa from the Early Cretaceous (e.g.,
Iguanacolossus, Hippodraco, and Theiophytalia) than to more basally situated taxa
from the Jurassic (e.g., Camptosaurus, Uteodon). This taxonomic work is
supplemented by field work that relocated the type locality, confirming its
provenance from unit L2 (lower Fuson Member equivalent) of the Lakota Formation.
Those data, combined with recently revised ages for the members of the Lakota
Formation based on charophyte and ostracod biostratigraphy, constrain the age of
this taxon to the late Valanginian to early Barremian.
PMID- 26417542
TI - Metatranscriptomic analysis of a high-sulfide aquatic spring reveals insights
into sulfur cycling and unexpected aerobic metabolism.
AB - Zodletone spring is a sulfide-rich spring in southwestern Oklahoma characterized
by shallow, microoxic, light-exposed spring water overlaying anoxic sediments.
Previously, culture-independent 16S rRNA gene based diversity surveys have
revealed that Zodletone spring source sediments harbor a highly diverse microbial
community, with multiple lineages putatively involved in various sulfur-cycling
processes. Here, we conducted a metatranscriptomic survey of microbial
populations in Zodletone spring source sediments to characterize the relative
prevalence and importance of putative phototrophic, chemolithotrophic, and
heterotrophic microorganisms in the sulfur cycle, the identity of lineages
actively involved in various sulfur cycling processes, and the interaction
between sulfur cycling and other geochemical processes at the spring source.
Sediment samples at the spring's source were taken at three different times
within a 24-h period for geochemical analyses and RNA sequencing. In depth mining
of datasets for sulfur cycling transcripts revealed major sulfur cycling pathways
and taxa involved, including an unexpected potential role of Actinobacteria in
sulfide oxidation and thiosulfate transformation. Surprisingly, transcripts
coding for the cyanobacterial Photosystem II D1 protein, methane monooxygenase,
and terminal cytochrome oxidases were encountered, indicating that genes for
oxygen production and aerobic modes of metabolism are actively being transcribed,
despite below-detectable levels (<1 uM) of oxygen in source sediment. Results
highlight transcripts involved in sulfur, methane, and oxygen cycles, propose
that oxygenic photosynthesis could support aerobic methane and sulfide oxidation
in anoxic sediments exposed to sunlight, and provide a viewpoint of microbial
metabolic lifestyles under conditions similar to those seen during late Archaean
and Proterozoic eons.
PMID- 26417543
TI - A comparison of two gluteus maximus EMG maximum voluntary isometric contraction
positions.
AB - Background. The purpose of this study was to compare the peak electromyography
(EMG) of the most commonly-used position in the literature, the prone bent-leg
(90 degrees ) hip extension against manual resistance applied to the distal thigh
(PRONE), to a novel position, the standing glute squeeze (SQUEEZE). Methods.
Surface EMG electrodes were placed on the upper and lower gluteus maximus of
thirteen recreationally active females (age = 28.9 years; height = 164 cm; body
mass = 58.2 kg), before three maximum voluntary isometric contraction (MVIC)
trials for each position were obtained in a randomized, counterbalanced fashion.
Results. No statistically significant (p < 0.05) differences were observed
between PRONE (upper: 91.94%; lower: 94.52%) and SQUEEZE (upper: 92.04%; lower:
85.12%) for both the upper and lower gluteus maximus. Neither the PRONE nor
SQUEEZE was more effective between all subjects. Conclusions. In agreement with
other studies, no single testing position is ideal for every participant.
Therefore, it is recommended that investigators employ multiple MVIC positions,
when possible, to ensure accuracy. Future research should investigate a variety
of gluteus maximus MVIC positions in heterogeneous samples.
PMID- 26417546
TI - Consequences of life history switch point plasticity for juvenile morphology and
locomotion in the Tungara frog.
AB - Many animals with complex life cycles can cope with environmental uncertainty by
altering the timing of life history switch points through plasticity. Pond
hydroperiod has important consequences for the fitness of aquatic organisms and
many taxa alter the timing of life history switch points in response to habitat
desiccation. For example, larval amphibians can metamorphose early to escape
drying ponds. Such plasticity may induce variation in size and morphology of
juveniles which can result in carry-over effects on jumping performance. To
investigate the carry-over effects of metamorphic plasticity to pond drying, we
studied the Tungara frog, Physalaemus pustulosus, a tropical anuran that breeds
in highly ephemeral habitats. We conducted an outdoor field mesocosm experiment
in which we manipulated water depth and desiccation and measured time and size at
metamorphosis, tibiofibula length and jumping performance. We also conducted a
complimentary laboratory experiment in which we manipulated resources, water
depth and desiccation. In the field experiment, metamorphs from dry-down
treatments emerged earlier, but at a similar size to metamorphs from constant
depth treatments. In the laboratory experiment, metamorphs from the low depth and
dry-down treatments emerged earlier and smaller. In both experiments, frogs from
dry-down treatments had relatively shorter legs, which negatively impacted their
absolute jumping performance. In contrast, reductions in resources delayed and
reduced size at metamorphosis, but had no negative effect on jumping performance.
To place these results in a broader context, we review past studies on carry-over
effects of the larval environment on jumping performance. Reductions in mass and
limb length generally resulted in lower jumping performance across juvenile
anurans tested to date. Understanding the consequences of plasticity on size,
morphology and performance can elucidate the linkages between life stages.
PMID- 26417547
TI - PopAlu: population-scale detection of Alu polymorphisms.
AB - Alu elements are sequences of approximately 300 basepairs that together comprise
more than 10% of the human genome. Due to their recent origin in primate
evolution some Alu elements are polymorphic in humans, present in some
individuals while absent in others. We present PopAlu, a tool to detect
polymorphic Alu elements on a population scale from paired-end sequencing data.
PopAlu uses read pair distance and orientation as well as split reads to identify
the location and precise breakpoints of polymorphic Alus. Genotype calling
enables us to differentiate between homozygous and heterozygous carriers, making
the output of PopAlu suitable for use in downstream analyses such as genome-wide
association studies (GWAS). We show on a simulated dataset that PopAlu calls Alu
elements inserted and deleted with respect to a reference genome with high
accuracy and high precision. Our analysis of real data of a human trio from the
1000 Genomes Project confirms that PopAlu is able to produce highly accurate
genotype calls. To our knowledge, PopAlu is the first tool that identifies
polymorphic Alu elements from multiple individuals simultaneously, pinpoints the
precise breakpoints and calls genotypes with high accuracy.
PMID- 26417548
TI - Epidemiological Studies of Substance Dependence and Abuse in Adults.
AB - Drug and alcohol use disorders account for a high and potentially preventable
proportion of overall disability and mortality. This article reviews published
data on the distribution of alcohol and drug abuse and dependence in the USA.
Published data shows that alcohol use disorders are more prevalent than illegal
drug use disorders, although the persistence of both disorders was similar over a
three-year follow-up period. Significant variability exists within sex,
racial/ethnic, and age groups. Men, Native Americans, and young adults, aged 18
to 25, are at a higher risk of substance dependence. Environmental correlates of
disorder include early environmental factors, political environment, and social
contextual factors. Systematically identifying, and measuring variability across
demographic populations, will guide prevention and intervention efforts. Future
research will expand understanding of the complex interplay between individual
and environmental factors that serve to initiate and sustain alcohol and drug use
disorders.
PMID- 26417549
TI - EEG Abnormalities in Children with Speech and Language Impairment.
AB - INTRODUCTION: Epilepsy, a chronic condition of recurrent seizures, affects
language, but the extent and nature of the language disturbance varies widely
according to the type, severity, and cause of the epilepsy. There is paucity of
literature on the electroencephalographic abnormalities in children with speech
and language impairment. The present study was therefore planned to find the
association of epileptiform EEG abnormalities in children with speech and
language impairment and if present, their localization and lateralization to the
language areas of the brain that are present predominantly in the left
hemisphere. MATERIALS AND METHODS: The study was conducted on Paediatric patients
having speech and language impairment (n=94, age-2 to 8 years) selected on the
basis of detailed history and neurologic examination. Video
Electroencephalography (EEG) was performed as per American Clinical
Neurophysiology Society guidelines using 16 channel RMS computerized EEG machine
for a minimum of 40 minutes to capture both wakefulness and sleep along with
activation procedures like hyperventilation (if feasible) and photic stimulation.
EEG was reviewed for any abnormal EEG background, benign variants, interictal
epileptiform discharges and ictal discharges. RESULTS: In our cohort, 19.7% boys
and 22.2% girls presented with seizures in their infancy and this gender
difference was found to be statistically significant (p<0.05). EEG was abnormal
in 47.9% children (45 out of 94) with no significant gender difference.
Epileptiform EEG was seen in 73.6% of children with history of seizures and 41.3%
of children without history of seizures (p<0.05). The EEG abnormities included:
abnormal background (64.5%), presence of generalized interictal epileptiform
discharges (57.8%), focal epileptiform discharges (20%) exclusively from left
hemisphere and multifocal interictal epileptiform discharges (33.3%), each
occurring in isolation or associated with other abnormities. CONCLUSION: In the
current study, it is definite that presence of generalized abnormalities in EEG
are seen in higher frequency and focal interictal epileptiform discharges are
solely seen in left hemisphere in children with speech and language impairment.
Although, there is no distinct pattern of EEG abnormalities in such patients, we
recommend a routine EEG in them and also brain imaging to complement the EEG
findings.
PMID- 26417545
TI - Intrinsically disordered caldesmon binds calmodulin via the "buttons on a string"
mechanism.
AB - We show here that chicken gizzard caldesmon (CaD) and its C-terminal domain
(residues 636-771, CaD136) are intrinsically disordered proteins. The
computational and experimental analyses of the wild type CaD136 and series of its
single tryptophan mutants (W674A, W707A, and W737A) and a double tryptophan
mutant (W674A/W707A) suggested that although the interaction of CaD136 with
calmodulin (CaM) can be driven by the non-specific electrostatic attraction
between these oppositely charged molecules, the specificity of CaD136-CaM binding
is likely to be determined by the specific packing of important CaD136 tryptophan
residues at the CaD136-CaM interface. It is suggested that this interaction can
be described as the "buttons on a charged string" model, where the electrostatic
attraction between the intrinsically disordered CaD136 and the CaM is solidified
in a "snapping buttons" manner by specific packing of the CaD136 "pliable
buttons" (which are the short segments of fluctuating local structure condensed
around the tryptophan residues) at the CaD136-CaM interface. Our data also show
that all three "buttons" are important for binding, since mutation of any of the
tryptophans affects CaD136-CaM binding and since CaD136 remains CaM-buttoned even
when two of the three tryptophans are mutated to alanines.
PMID- 26417550
TI - Hirschsprung's Disease in Neonates with Special Reference to Calretinin
Immunohistochemistry.
AB - BACKGROUND: Hirschsprung's disease is a classic example of a complex genetic
disease, characterized by the lack of enteric ganglia in the submucosal and
myenteric plexuses, along variable portions of the distal gut. The diagnosis of
Hirschsprung's disease is based on a combination of clinical features,
radiological appearance of the bowel and histological features in Haematoxylin &
Eosin stained sections of intestinal biopsies. Calretinin Immunohistochemistry is
emerging to be one of the newer methods. AIMS AND OBJECTIVES: This study was
undertaken to ascertain 1) clinical profile; 2) mode of presentation; 3) to
evaluate the role of Calretinin immunostain in the diagnosis of Hirschsprung's
Disease. MATERIALS AND METHODS: This prospective and observational study was
conducted in the Department of Pathology IPGME&R from July 2013 to September
2014. Eighty nine patients, clinically and radiologically diagnosed with
Hirschsprung's disease underwent surgery and were included in the study. The data
of every patient including age, sex and presenting symptoms were recorded.
Eventually, histopathological examination & immunohistochemistry were done.
RESULTS: Total number of cases studied was 89 which aged between 0 days to 28
days. Overall sensitivity in our study to diagnose presence or absence of
ganglion cells by calretinin immunohistochemistry was 100% and the specificity is
97.44% with positive and negative predictive value of 84.62 % and 100 %
respectively. CONCLUSION: Calretinin immunohistochemistry holds several
advantages, and it's simple and not doubtful; and it is either positive or
negative.
PMID- 26417551
TI - Stevens Johnson Syndrome-Toxic Epidermal Necrolysis Overlap Secondary to
Interaction Between Methotrexate and Etoricoxib: A Case Report.
AB - Rheumatoid arthritis (RA) is an autoimmune disease affecting about 1% of people,
with the highest incidence between 40 and 70 years. Methotrexate is an anti
folate analogue that has good efficacy and safety in the treatment of RA.
Methotrexate (MTX) and non-steroidal anti inflammatory drugs are often
concomitantly administered in clinical practice for the treatment of RA. In this
case report, a 57-year-old female was treated with oral methotrexate 7.5 mg per
week for a diagnosed case of RA. Since her pain persisted after completing six
weeks of treatment with methotrexate, oral etoricoxib 60 mg once daily was added
to the treatment regimen. Six weeks later, the patient complained of oral
ulcerations and blisters on all fours limbs and trunk. The patient was re
evaluated and was diagnosed with Stevens-Johnson syndrome-Toxic epidermal
necrolysis (SJS-TEN) overlap. This case highlights the possible pharmacokinetic
interaction between methotrexate and etoricoxib that has a significant clinical
implication.
PMID- 26417553
TI - Is Endoscopy Really Necessary in My Case? A Four Year Retrospective Study.
AB - INTRODUCTION: About 40% of the general population report dyspepsia at some time
in their life making it a fairly common disease. Uncomplicated dyspepsia refers
to patients whose dyspepsia is not accompanied by alarm features or associated
with NSAIDS usage. AIM: To assess the need for UGI Endoscopy and find out the
patterns of different endoscopic presentations in patients presenting with
uncomplicated dyspepsia. MATERIALS AND METHODS: Our study conducted in KR
Hospital, Mysore, Department of General Surgery is a retrospective endoscopic
study of 1450 patients with uncomplicated dysepsia. RESULTS: A significant 64% of
the patients presenting with uncomplicated dyspepsia were found to have findings
on endoscopy. The most common age range for positive endoscopic findings was 40
50 years in our hospital. Malignancy was diagnosed in 2.5% patients. CONCLUSION:
We recommend upper GI endoscopy in patients presenting with uncomplicated
dyspepsia for patients above 40 years of age in our hospital.
PMID- 26417552
TI - Spontaneous Soft Tissue Haematomas- A Rare Presentation of Chronic Myeloid
Leukemic (CML).
AB - Spontaneous soft tissue haematomas are rarely found in haematological
malignancies. Chronic myeloid leukemia (CML) is a myeloproliferative disorder
which rarely present with thrombo-haemorrhagic phenomenon. It is a malignant
clonal disorder of pleuripotent stem cells that results in increase in myeloid,
erythroid and platelets cells in peripheral blood and marked myeloid hyperplasia
in bone marrow. It is characterized by the presence of Philadelphia chromosome
(Ph) with BCR - ABL 1 fusion gene. This gene is responsible for the formation of
210 KDa chimeric proteins with enhanced tyrosine kinase activity which leads to
the abnormal bone marrow cell proliferation and to the clinical and morphologic
manifestations of leukemia. Cutaneous and mucous membrane bleeding is common in
CML whereas bleeding in deep soft tissue is rarely found because of qualitative
and quantitative platelet abnormalities. Here, we report a case of CML (BCR-ABL
rearrangement positive) who presented with large haematoma in the anterior as
well as posterior compartment of left thigh and treated successfully with
hydroxyurea and imatinib.
PMID- 26417554
TI - Cd34 and Mast Cell Analysis in Normal Oral Mucosa and Different Grades of Oral
Squamous Cell Carcinoma: A Comparative Study.
AB - BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) remains a serious health problem
worldwide. Prognosis of OSCC is poor and long term survival rate still remains
below 50%. Angiogenesis or neovascularisation plays an important role in tumour
progression and metastasis. Mast cells have been implicated in promoting tumour
angiogenesis, especially of digestive tract, little is known in OSCC. AIM &
OBJECTIVE: To study the correlation between blood vessel density (BVD) and mast
cell density (MCD) in different grades of OSCC. MATERIALS AND METHODS: METHODS:
Thirty eight paraffin blocks of different grades of OSCC were retrieved from the
department and sections were stained with CD34 followed by counterstaining with
toluidine blue. The slides were then analysed using Leica Software (Version 4.5).
RESULTS: Mean BVD and MCD were found to be increased in OSCC as compared to
normal mucosa. Increase in BVD with co-current increase in MCD was also observed
in different grades of OSCC. CONCLUSION: From our study, it was concluded that,
mast cells play a major role in promoting tumour angiogenesis. But, as the grade
of the tumour increases, other angiogenic factors may play a more significant
role than mast cells in tumour progression.
PMID- 26417555
TI - Class II Division 1 in New Dimension: Role of Posterior Transverse Interarch
Discrepancy in Class II Division 1 Malocclusion During the Mixed Dentition
Period.
AB - INTRODUCTION: Posterior transverse discrepancy as seen in some cases of Class II
Division 1 malocclusion in mixed dentition period can be related to typical
skeletofacial characteristics. These features when studied early in the mixed
dentition period give a clear view of the desired appropriate treatment plan in a
particular case. AIM: The purpose of this study was to establish a simple method
to determine the posterior (intermolar) transverse discrepancy and craniofacial
skeletal features between the dental arches during the mixed dentition in a
sample of Class II Division 1 patients to provide diagnostic and therapeutic
guidance in the early approach. MATERIALS AND METHODS: A sample of 60 Class II
Division 1 patients in mixed dention that were divided into 30 Class II Division
1 patients with posterior transverse interarch discrepancy {Class II (I) PTID
group} and 30 Class II Division 1 patients without posterior transverse interarch
discrepancy {Class II (I) NPTID group}. Thirty Class I subjects in mixed
dentition were included as control. RESULTS: The skeletal features of the Class
II group without PTID are those of the skeletal Class II associated with
'anatomic' mandibular retrusion (due to a micrognathic mandible) and those of the
Class II group with PTID as skeletal Class II associated with only a 'functional'
mandibular retrusion (due to a posteriorly displaced mandible of normal size).
CONCLUSION: This study confirmed the role of occlusion in the control of
maxillomandibular skeletal relationships.The treatment strategies could be
planned on the basis of the transverse component of Class II Division 1 groups in
the mixed dentition period.
PMID- 26417556
TI - Amplification of Cellular Oncogenes in Solid Tumors.
AB - The term gene amplification refers to an increase in copy number of a gene.
Upregulation of gene expression through amplification is a general mechanism to
increase gene dosage. Oncogene amplifications have been shown in solid human
cancers and they are often associated with progression of cancer. Defining
oncogene amplification is useful since it is used as a prognostic marker in
clinical oncology nowadays, especially v-erb-b2 avian erythroblastic leukemia
viral oncogene homolog 2 (HER2) targeted agents are used in breast cancer
patients with high level of HER2 overexpression as a therapeutic approach.
However, patients without HER2 overexpression do not appear to benefit from these
agents. We concluded that determination of oncogene amplification in solid tumors
is an important factor in treatment of human cancers with many unknowns. We have
referred to PubMed and some databases to prepare this article.
PMID- 26417557
TI - Estimation of 10-Year Risk of Coronary Heart Disease in Nepalese Patients with
Type 2 Diabetes: Framingham Versus United Kingdom Prospective Diabetes Study.
AB - BACKGROUND: Predicting future coronary heart disease (CHD) risk with the help of
a validated risk prediction function helps clinicians identify diabetic patients
at high risk and provide them with appropriate preventive medicine. AIM: The aim
of this study is to estimate and compare 10-year CHD risks of Nepalese diabetic
patients using two most common risk prediction functions: The Framingham risk
equation and United Kingdom Prospective Diabetes Study (UKPDS) risk engine that
are yet to be validated for Nepalese population. PATIENTS AND METHODS: We
conducted a hospital-based, cross-sectional study on 524 patients with type 2
diabetes. Baseline and biochemical variables of individual patients were recorded
and CHD risks were estimated by the Framingham and UKPDS risk prediction
functions. Estimated risks were categorized as low, medium, and high. The
estimated CHD risks were compared using kappa statistics, Pearson's bivariate
correlation, Bland-Altman plots, and multiple regression analysis. RESULTS: The
mean 10-year CHD risks estimated by the Framingham and UKPDS risk functions were
17.7 +/- 12.1 and 16.8 +/- 15 (bias: 0.88, P > 0.05), respectively, and were
always higher in males and older age groups (P < 0.001). The two risk functions
showed moderate convergent validity in predicting CHD risks, but differed in
stratifying them and explaining the patients' risk profile. The Framingham
equation predicted higher risk for patients usually below 70 years and showed
better association with their current risk profile than the UKPDS risk engine.
CONCLUSIONS: Based on the predicted risk, Nepalese diabetic patients,
particularly those associated with increased numbers of risk factors, bear higher
risk of future CHDs. Since this study is a cross-sectional one and uses
externally validated risk functions, Nepalese clinicians should use them with
caution, and preferably in combination with other guidelines, while making
important medical decisions in preventive therapy of CHD.
PMID- 26417558
TI - The Pattern of Psoriatic Arthritis in Kashmir: A 6-Year Prospective Study.
AB - BACKGROUND: The prevalence, clinical presentation, and patterns of psoriatic
arthritis (PsA) vary in different parts of the world. The scenario of PsA in west
is different from that of Asia. Moreover, the oligoarticular type which was
considered most prevalent earlier has been replaced by polyarticular type. AIM:
The study was to the clinical profile of psoriasis patients associated with PsA
in Kashmir valley of India. MATERIALS AND METHODS: This was a noninterventional,
observational, prospective, hospital-based study involving 150 successive
patients of PsA over a span of 6 years. Severity of the skin and nail involvement
was assessed by Psoriasis Area and Severity Index (PASI) and Nail Psoriasis
Severity Index (NAPSI), respectively. PsA was diagnosed by classification
criteria for PsA. The number and pattern of swollen and tender joints was counted
and classified by Moll and Wright's classification criteria. RESULTS: Plaque-type
psoriasis was the most common clinical type, observed in 122 (81.33%) patients
followed by erythrodermic psoriasis in 10 (6.66%) patients and pustular psoriasis
in eight (5.33%) patients. PsA occurred between 30 and 40 years of age in 105
(70%) patients. The cutaneous involvement occurred before joint involvement in
113 (75.33%), while they occurred simultaneously in 30 (20%) cases and the PsA
preceded the skin involvement in seven (4.66%) cases. Symmetrical polyarthritis
was the commonest clinical presentation and was seen in 90 (60%) patients. Nail
involvement due to psoriasis was present in 120 (80%) patients. Commonest nail
change found was pitting and seen in 60 (40%) patients. CONCLUSION: The clinical
pattern of PsA varies in different parts of the world. Knowledge of the clinical
presentation of PsA in a given area is necessary for the successful management of
this disease.
PMID- 26417559
TI - Multidetector Computed Tomography and Magnetic Resonance Imaging Evaluation of
Craniovertebral junction Abnormalities.
AB - BACKGROUND: Craniovertebral junction (CVJ) abnormalities constitute an important
group of treatable neurological disorders with diagnostic dilemma. Their precise
diagnosis, identification of probable etiology, and pretreatment evaluation
significantly affects prognosis and quality of life of patients. AIMS: The study
was to classify various craniovertebral junction disorders according to their
etiology and to define the importance of precise diagnosis for pretreatment
evaluation with multidetector computed tomography (MDCT) and magnetic resonance
imaging (MRI). MATERIALS AND METHODS: This is a prospective observational study
of 62 patients referred to our department between October 2012 and September
2014. All patients suspected to have a craniovertebral junction disorder were
included in the study, from all age groups and both genders. Detailed clinical
history was taken. Radiographs of cervical spine were collected if available. All
patients were subjected to MDCT and/or MRI. RESULTS: In our study of 62 patients;
39 were males and 23 were females, with male to female ratio of 1.6:1. Most
common age group was 2(nd) -3(rd) decade (19 patients, 30.64%). Developmental
anomalies (33 patients, 53.22%) were the most common etiology group followed by
traumatic (10 patients, 16.12%), degenerative (eight patients, 12.90%), infective
(four patients, 6.45%), inflammatory and neoplastic (three patients each, 4.8%),
and no cause found in one patient. CONCLUSIONS: CVJ abnormalities constitute an
important group of treatable neurological disorders, especially in certain ethnic
groups and are approached with much caution by clinicians. Thus, it is essential
that radiologists should be able to make a precise diagnosis of craniovertebral
junction abnormalities, classify them into etiological group, and rule out
important mimickers on MDCT and/or MRI, as this information ultimately helps
determine the management of such abnormalities, prognosis, and quality of life of
patients.
PMID- 26417560
TI - Hypoplasia of the Spleen: Review of Pathogenesis, Diagnosis, and Potential
Clinical Implications.
AB - CONTEXT: Splenic aplasia is seen when the spleen is congenitally absent, has been
surgically removed, or becomes atrophic secondary to episodes of arterial/venous
occlusion, which result in splenic infarction. This rare condition is caused by a
heterogenous group of diseases, which may present a wide spectrum of clinical
manifestations. Splenic hypoplasia is defined as reduction in splenic mass and or
functions caused by incomplete splenic development or secondary parenchymal
involution. Splenic infarction may be clinically silent and only discovered
incidentally during abdominal exploration for other conditions. CASE REPORT: We
present an unusual case of hypoplastic spleen with calcifications, which was
preoperatively found during radiologic workup for gastric carcinoma. An 88-year
old woman presented with coffee-ground emesis. Her past medical history was only
significant for atrial fibrillation. Esophagogastroduodenoscopy demonstrated
gastric carcinoma, for which a subtotal gastrectomy was planned. Preoperative
computed tomography scan showed a hypoplastic spleen with calcifications in the
left upper quadrant. Symptoms of immunologic deficiency were not present. During
laparotomy, an atrophied and calcified spleen was identified and left in situ.
The patient made an uneventful postoperative recovery. Splenic hypoplasia is an
unique entity, which may be seen in the setting of atrial fibrillation and
abdominal malignancy. CONCLUSION: Splenic hypoplasia may be detected incidentally
during radiologic workup or abdominal exploration. Abdominal symptoms or
immunologic deficiency are not always present.
PMID- 26417561
TI - Double Right Coronary Artery Originating from Separate Ostia: A Report of Two
Cases.
AB - CONTEXT: Coronary artery anomalies are uncommon and most are incidental findings.
Double right coronary artery (RCA) is a very rare coronary artery anomaly. CASE
REPORT: We report two cases of double RCA incidentally found in electrocuted
patients. Both cases showed double RCA arising from separate ostia. On
microscopy, both right coronaries showed no significant pathology in the first
case while in the second case, the posterior RCA showed features of obliterative
arteritis. CONCLUSION: Although double coronary artery has been regarded as
hemodynamically insignificant, it may be associated with atherosclerosis, acute
coronary syndromes, and other anomalies. It is important to know the anatomic
variants. Meticulous grossing and careful observation could unearth hidden
anomalies.
PMID- 26417562
TI - Hyperhomocysteinemia Association With Transient Global Amnesia: A Rare Case
Report.
AB - CONTEXT: Transient global amnesia (TGA) is an intriguing condition that
classically presents with an abrupt onset of temporary complete anterograde
amnesia and partial retrograde amnesia. Most individuals who experience such a
form of amnesia usually have only one attack but recurrent attacks are possible.
Most attacks last for a few minutes or few hours and the ability to lay down new
memories may also be affected but gradually improves, leaving only a dense
amnestic gap for the duration of the episode. There has been some discussion
about the etiology behind TGA; however, there has yet to be a consensus with
regard to any significant association. CASE REPORT: We report the case of a 65
year-old male presenting with a sudden onset of memory loss that is typical of
TGA and who was found to have elevated homocysteine levels. There has only been
one other case previously reported that discussed a possible correlation between
hyperhomocysteinemia and TGA. It is yet to be determined if increased
homocysteine level is a significant risk factor for attacks of TGA. CONCLUSION:
Although it was first described more than half a century ago, it can still be
misdiagnosed frequently as many physicians are not familiar with this condition.
Furthermore, there are quite a few medical conditions that may cause sudden
memory impairment, such as epilepsy and stroke, which make it difficult to
distinguish them from this form of amnesia. The knowledge of these clinical
identities is necessary for a high index of suspicion, which may lead to a
meticulous medical evaluation as required for proper diagnosis.
PMID- 26417563
TI - Myanmar: An Endemic Country for Oral Cancer.
PMID- 26417564
TI - Erratum to: Diet, exercise or diet with exercise: comparing the effectiveness of
treatment options for weight-loss and changes in fitness for adults (18-65 years
old) who are overfat, or obese; systematic review and meta-analysis.
AB - [This corrects the article DOI: 10.1186/s40200-015-0154-1.].
PMID- 26417565
TI - Evaluation of the reproducibility of the AO/ASIF classification for humeral shaft
fractures.
AB - OBJECTIVE: To evaluate the reproducibility of the AO/Asif classification for
humeral shaft fractures. METHODS: Consecutive radiographs of the arm in both
anteroposterior and lateral view from 60 patients with humeral shaft fractures
were analyzed. Six observers who were familiar with the AO/Asif classification
(three shoulder and elbow surgery specialists and three general orthopedists)
were selected to make the analysis, which was done at three different times. The
data were subjected to statistical analysis using the kappa coefficient. RESULTS:
The intra and interobserver concordance was statistically significant in all the
analyses. CONCLUSIONS: All the evaluators showed concordance between the three
evaluations that was considered to be statistically significant. However, the
highest values were found among the specialists.
PMID- 26417567
TI - Evaluation of the results from non-arthroplastic treatment (arthroscopy) for
shoulder arthrosis.
AB - OBJECTIVES: To evaluate the functional results from patients with arthrosis who
underwent an arthroscopic procedure, in an attempt to correlate these results
with the patients' epidemiological profile, surgical technique used, possible
complications and postoperative protocol. METHODS: Between 1998 and 2011, 31
patients (32 shoulders) with shoulder arthrosis underwent arthroscopic treatment
performed by the Shoulder and Elbow Group of the Department of Orthopedics and
Traumatology of Santa Casa de Sao Paulo. Primary or secondary cases of shoulder
arthrosis under the age of 70 years, in which the rotator cuff was intact, were
included. Furthermore, cases in which, despite an indication for an arthroplastic
procedure, an attempt to perform an alternative procedure had been chosen, were
also included. The following were evaluated: sex, age, dominance, comorbidities,
length of time with complaint, associated lesions, etiology, previous treatment,
operation performed, postoperative protocol and pre and postoperative active
ranges of motion. The functional evaluation was conducted using the UCLA
criteria, before and after the operation. The joint cartilage alterations were
classified in accordance with Outerbridge and the arthrosis by means of Walch.
RESULTS: There were statistically significant mean differences in the values for
elevation, lateral rotation and medial rotation from before to after the
operation (p < 0.001) and there was a tendency (p = 0.057) toward poor results
with greater length of time with complaints before the surgery. The total gain in
UCLA score did not have any statistically significant relationship with any of
the other variables analyzed. CONCLUSION: Arthroscopic treatment of glenohumeral
arthrosis provided functional improvement of the glenohumeral joint, with
significant gains in elevation and lateral and medial rotation, and improvements
in function and pain. Greater length of time with complaints was a factor
strongly suggestive of worse results.
PMID- 26417566
TI - Preliminary results from osteosynthesis using Ender nails by means of a
percutaneous technique, in humeral diaphysis fractures in adults.
AB - OBJECTIVE: To demonstrate the clinical and functional results from treatment of
humeral diaphysis fractures using Ender nails. METHODS: Eighteen patients who
underwent osteosynthesis of humeral diaphysis fractures using Ender nails were
evaluated. In addition to the clinical and radiographic evaluations, patients
with a minimum of one year of follow-up were assessed by means of the Constant,
American Shoulder and Elbow Surgeons (ASES), Mayo Clinic and Simple Shoulder
Value (SSV) functional scores, and in relation to the degree of satisfaction with
the final result. The fixation technique used was by means of an anterograde
percutaneous route. RESULTS: All the patients achieved fracture consolidation,
after a mean of 2.9 months (ranging from 2 to 4 months). The mean Constant score
was 85.7 (ranging from 54 to 100) and the mean ASES score was 95.9 (ranging from
76 to 100). All the patients achieved the maximum score on the Mayo Clinic scale.
CONCLUSION: Fixation of humeral diaphysis fractures using Ender nails by means of
a percutaneous technique was shown to be a method with promising preliminary
results.
PMID- 26417568
TI - Partial rotator cuff injury in athletes: bursal or articular?
AB - A painful shoulder is a very common complaint among athletes, especially in the
case of those in sports involving throwing. Partial lesions of the rotator cuff
may be very painful and cause significant functional limitation to athletes'
sports practice. The incidence of partial lesions of the cuff is variable (13
37%). It is difficult to make the clinical and radiological diagnosis, and this
condition should be borne in mind in the cases of all athletes who present
symptoms of rotator cuff syndrome, including in patients who are diagnosed only
with tendinopathy. OBJECTIVE: To evaluate the epidemiological behavior of partial
lesions of the rotator cuff in both amateur and professional athletes in
different types of sports. METHODS: We evaluated 720 medical files on athletes
attended at the shoulder service of the Discipline of Sports Medicine at the
Sports Traumatology Center, Federal University of Sao Paulo. The majority of them
were men (65%). Among all the patients, 83 of them were diagnosed with partial
lesions of the rotator cuff, by means of ultrasonography or magnetic resonance,
or in some cases using both. We applied the binomial test to compare the
proportions found. RESULT: It was observed that intra-articular lesions
predominated (67.6%) and that these occurred more frequently in athletes in
sports involving throwing (66%). Bursal lesions occurred in 32.4% of the
athletes, predominantly in those who did muscle building (75%). CONCLUSION: Intra
articular lesions are more frequent than bursal lesions and they occur
predominantly in athletes in sports involving throwing, while bursal lesions were
more prevalent in athletes who did muscle building.
PMID- 26417571
TI - Anatomical reconstruction of the anterior cruciate ligament: a logical approach.
AB - We describe the surgical approach that we have used over the last years for
anterior cruciate ligament (ACL) reconstruction, highlighting the importance of
arthroscopic viewing through the anteromedial portal (AMP) and femoral tunnel
drilling through an accessory anteromedial portal (AMP). The AMP allows direct
view of the ACL femoral insertion site on the medial aspect of the lateral
femoral condyle, does not require guides for anatomic femoral tunnel reaming,
prevents an additional lateral incision in the distal third of the thigh (as
would be unavoidable when the outside-in technique is used) and also can be used
for double-bundle ACL reconstruction.
PMID- 26417569
TI - Magnetic resonance study on the anatomical relationship between the posterior
proximal region of the tibia and the popliteal artery.
AB - OBJECTIVE: To analyze and describe the distance from the popliteal artery to
three specific areas of the proximal region of the tibia, with the knee extended,
by means of magnetic resonance. METHODS: Images of 100 knees of patients who
underwent magnetic resonance examinations were analyzed. The location of the
popliteal artery was measured in three different areas of the posterior proximal
region of the tibia. The first measurement was made at the level of the knee
joint (tibial plateau). The second was 9 mm distally to the tibial plateau. The
third was at the level of the anterior tuberosity of the tibia (ATT). RESULTS:
The distances between the popliteal artery and the tibial plateau and ATT region
were significantly greater in males than in females. The distances between the
popliteal artery and the regions 9 mm distally to the tibial plateau and the ATT
were significantly greater in the age group over 36 years than in the group <=36
years. CONCLUSION: Knowledge of the anatomical position of the popliteal artery,
as demonstrated through magnetic resonance studies, is of great relevance in
planning surgical procedures that involve the knee joint. In this manner,
devastating iatrogenic injuries can be avoided, particularly in regions that are
proximal to the tibial plateau and in young patients.
PMID- 26417570
TI - Gluteal pain in athletes: how should it be investigated and treated?
AB - Gluteal pain is a frequent symptom in athletes, and defining it etiologically is
a challenge for orthopedists. In the present study, using an anatomical approach
to the posterior region of the pelvis and the proximal femur, divided into four
quadrants, systematized investigation is proposed with the aim of optimizing the
treatment and accelerating athletes' return to their sport, through correct
diagnosis.
PMID- 26417572
TI - Disordered ripples are a common feature of genetically distinct mouse models
relevant to schizophrenia.
AB - We present results from a novel comparative approach to the study of mechanisms
of psychiatric disease. Previous work examined neural activity patterns in the
hippocampus of a freely behaving mouse model associated with schizophrenia, the
calcineurin knockout mouse. Here we examined a genetically distinct mouse that
exhibits a similar set of behavioral phenotypes associated with schizophrenia, a
transgenic model expressing a putative dominant-negative DISC1 (DN-DISC1).
Strikingly, the principal finding of the earlier work is replicated in the DN
DISC1 mice, that is, a selective increase in the numbers of sharp-wave ripple
events in the local hippocampal LFP, while at the same time other LFP patterns
such as theta and gamma are unaffected. Sharp-wave ripples are thought to arise
from hippocampal circuits, and reflect the coordinated activity of the principal
excitatory cells of the hippocampus, in specific patterns that represent
reactivated memories of previous experiences and imagined future experiences that
predict behavior. These findings suggest that multiple genetic alterations could
converge on distinct patterns of aberrant neurophysiological function to give
rise to common behavioral phenotypes in psychiatric disease.
PMID- 26417573
TI - A potential osteoporosis target in the FAS ligand/FAS pathway of osteoblast to
osteoclast signaling.
PMID- 26417574
TI - Achieving tissue specific levels of angiogenesis: Not(ch) a big deal!
PMID- 26417575
TI - Overcoming the hurdles of using PET/CT for target volume delineation in curative
intent radiotherapy of non-small cell lung cancer.
PMID- 26417576
TI - Comparison of self-reported and measured range of motion in total knee
arthroplasty patients.
AB - Total knee arthroplasty (TKA) is an established method used in the treatment of
end-stage knee osteoarthritis. Range of motion (ROM) and relief from pain show
success of TKA. One of the most important aims of this treatment is to achieve an
adequate ROM. Numerous outcome instruments and patient-reported questionnaires
are in use to evaluate of TKA patients. For this purpose, disease-specific
questionnaires and self-reported ROM and function evaluation tools are also being
developed. The most important criteria in musculoskeletal care is assessing the
joint mobility of the patient's. Joint mobility can be measured with visual
estimates, universal goniometer, X-ray radiography, digital gravity goniometers
and applications found in smart phones. Apart from the reliability and validity
of the method, obtaining the same results from different examiners is very
important. The clinical follow-up of patients is an important part of
postoperative care after TKA. The follow-up interval and duration remain
dependent on the physician's anticipation of the clinical progress of the
individual patient. Long-term surveillance of joint arthroplasty is necessary,
but it has also become increasingly burdensome as greater numbers of TKAs are
performed, and in younger populations. Patient self-reported questionnaires and
self-goniometric measurement are used by many investigators to decrease this
burden on the surgeon or staff, and in combination with telemedicine radiographs
might be a reasonable option to routine clinic visits. They could reasonably be
expected to lower the burden on both the patient and the clinician without
eliminating contact and thus sacrificing quality of care. At the same time, it
would reduce the financial burden too. Self-reported measured ROM can use in the
routine follow-ups to reduce surgeons, physiotherapist and other staff.
PMID- 26417577
TI - The potential utility of patient-reported range of motion after total knee
arthroplasty.
PMID- 26417578
TI - Lung metastasectomy: an experience-based therapeutic option.
PMID- 26417579
TI - Pulmonary lobectomies for patients with cognitive impairment: the importance of
postoperative respiratory care.
AB - BACKGROUND: Patients with cognitive impairment (CI) may have an increased risk of
complications after major thoracic surgery. However, little is known about this
risk and the corresponding management. METHODS: Clinical data of patients who
underwent pulmonary lobectomy via open thoracotomy between January 2006 and
December 2008 in our institution were retrospectively reviewed. RESULTS: Overall,
1,325 patients who underwent pulmonary lobectomy via open thoracotomy were
analyzed retrospectively, in which five patients were diagnosed with CI. Sputum
retention was common and led to significant hypoxemia in all five patients. Four
patients were re-intubated due to severe respiratory dysfunction, and three
underwent tracheotomy 7 days after intubation due to respiratory infection.
Regarding to duration of chest tube placement, length of hospital stay, morbidity
rate, and hospital cost, CI patients were significant higher compared with
cognitively normal patients undergoing lobectomy via open thoracotomy.
CONCLUSIONS: Patients with CI may have difficulties in expectoration after
pulmonary lobectomy, and develop multiple respiratory complications, thus
increasing hospital stay. Efficacious sputum and airway clearance is critical in
these patients.
PMID- 26417580
TI - Esophageal electric fields are predictive of atrial cardioversion success-a
finite element analysis.
AB - BACKGROUND: Atrial fibrillation (AF) is a debilitating cardiac arrhythmia, one
potential treatment of which is external cardioversion. Studies have shown
external cardioversion success is affected by electrode placement and that
esophageal electric fields (EEFs) during low strength shocks have the potential
to be used in determining patient-specific optimal electrode placements during
animal experiments. The objective of this study was to determine the relationship
between EEFs and atrial defibrillation thresholds (ADFTs) during computer
simulations using an anatomically realistic computer model of a human torso.
METHODS: Over 600 electrode placements were simulated during which EEFs were
compared to ADFTs. RESULTS: There was no single optimal electrode placement with
multiple electrode placements resulting in similarly low ADFTs. There was over
40% difference in the ADFTs between the most and least optimal electrode
configurations. There was no correlation between EEFs and ADFTs for all electrode
placements, but a strong negative correlation when small shifts from clinically
relevant electrode placements were performed. CONCLUSIONS: These results suggest
a small shifts protocol from clinically relevant electrode placements has the
potential to increase the probability of successful cardioversion on the first
shock and reduce the cumulative number of shocks and energy to which patients are
exposed.
PMID- 26417582
TI - Risk-reducing strategies for repair of complex ascending aortic false aneurysms.
AB - Late presentation of aortic false aneurysm following repair of acute type A
aortic dissection occurs in 10% to 24% of cases. This condition is associated
with high mortality if left untreated. Herein we describe a combination of
surgical strategies that we believe may be used effectively to reduce the
surgical risk of these complex operations.
PMID- 26417581
TI - Are anticoagulant independent mechanical valves within reach-fast prototype
fabrication and in vitro testing of innovative bi-leaflet valve models.
AB - BACKGROUND: Exploration for causes of prosthetic valve thrombogenicity has
frequently focused on forward or post-closure flow detail. In prior laboratory
studies, we uncovered high amplitude flow velocities of short duration close to
valve closure implying potential for substantial shear stress with subsequent
initiation of blood coagulation pathways. This may be relevant to widely accepted
clinical disparity between mechanical and tissue valves vis-a-vis
thrombogenicity. With a series of prototype bi-leaflet mechanical valves, we
attempt reduction of closure related velocities with the objective of identifying
a prototype valve with thrombogenic potential similar to our tissue valve
control. This iterative design approach may find application in preclinical
assessment of valves for anticoagulation independence. METHODS: Tested valves
included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented
early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi
steady flow systems were used for testing. Projected dynamic valve area (PDVA)
was measured using previously described novel technology. Flow velocity over the
open and closing periods was determined by volumetric flow rate/PDVA. For the
closed valve interval, use was made of data obtained from quasi-steady back
pressure/flow tests. Performance was ranked by a proposed thrombogenicity
potential index (TPI) relative to tissue and mechanical control valves. RESULTS:
Optimization of the prototype valve designs lead to a 3-D printed model (BV3D).
For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the
control mechanical valve (3.44/3.93) and similar to the control tissue valve
(ideal TPI <=1.0). CONCLUSIONS: Using unique technology, rapid prototyping and
thrombogenicity ranking, optimization of experimental valves for reduced
thrombogenic potential was expedited and simplified. Innovative mechanical valve
configurations were identified that merit consideration for further development
which may bring the anti-coagulation independent mechanical valve within reach.
PMID- 26417583
TI - Robotic-assisted right inferior lobectomy.
PMID- 26417584
TI - Robotic thymectomy in patients with myasthenia gravis by vascular
skeletonization.
PMID- 26417586
TI - Discontinuing epidermal growth factor receptor-tyrosine kinase inhibitor during
second-line chemotherapy: is the evidence strong enough?
PMID- 26417585
TI - If no difference in effectiveness is found between two treatments it may be
because the treatments are similarly ineffective.
PMID- 26417587
TI - Is fixation an option for comminuted femoral head fracture?
AB - Femoral head fracture (Pepkin fracture) is a serious injury that is usually
caused by trauma with more incidences in young age. There is no definitive
treatment suggested in literature for Pepkin fracture. In this work, a case with
class IV Pipkin fracture is presented. Fixation of the fracture was done and the
outcomes of the surgical procedure immediately and 6 years after surgery are
documented.
PMID- 26417588
TI - Professor Shi-Wen Wu: One City, One Doctor-building up the national DMD registry
network.
PMID- 26417589
TI - Prof. Hong Zhao, ATM's Associate Editor-in-Chief, honored with Beijing's 10
Outstanding Young Doctors Award.
PMID- 26417590
TI - Human Genes Encoding Transcription Factors and Chromatin-Modifying Proteins Have
Low Levels of Promoter Polymorphism: A Study of 1000 Genomes Project Data.
AB - The expression level of each gene is controlled by its regulatory regions, which
determine the precise regulation in a tissue-specific manner, according to the
developmental stage of the body and the necessity of a response to external
stimuli. Nucleotide substitutions in regulatory gene regions may modify the
affinity of transcription factors to their specific DNA binding sites, affecting
the transcription rates of genes. In our previous research, we found that genes
controlling the sensory perception of smell and genes involved in antigen
processing and presentation were overrepresented significantly among genes with
high SNP contents in their promoter regions. The goal of our study was to reveal
functional features of human genes containing extremely small numbers of SNPs in
promoter regions. Two functional groups were found to be overrepresented among
genes whose promoters did not contain SNPs: (1) genes involved in gene-specific
transcription and (2) genes controlling chromatin organization. We revealed that
the 5'-regulatory regions of genes encoding transcription factors and chromatin
modifying proteins were characterized by reduced genetic variability. One
important exception from this rule refers to genes encoding transcription factors
with zinc-coordinating DNA-binding domains (DBDs), which underwent extensive
expansion in vertebrates, particularly, in primate evolution. Hence, we obtained
new evidence for evolutionary forces shaping variability in 5'-regulatory regions
of genes.
PMID- 26417591
TI - Epitope Fingerprinting for Recognition of the Polyclonal Serum Autoantibodies of
Alzheimer's Disease.
AB - Autoantibodies (aAb) associated with Alzheimer's disease (AD) have not been
sufficiently characterized and their exact involvement is undefined. The use of
information technology and computerized analysis with phage display technology
was used, in the present research, to map the epitope of putative self-antigens
in AD patients. A 12-mer random peptide library, displayed on M13 phages, was
screened using IgG from AD patients with two repetitions. Seventy-one peptides
were isolated; however, only 10 were positive using the Elisa assay technique
(Elisa Index > 1). The results showed that the epitope regions of the
immunoreactive peptides, identified by phage display analysis, were on the
exposed surfaces of the proteins. The putative antigens MAST1, Enah, MAO-A,
X11/MINT1, HGF, SNX14, ARHGAP 11A, APC, and CENTG3, which have been associated
with AD or have functions in neural tissue, may indicate possible therapeutic
targets.
PMID- 26417593
TI - Corrigendum to "Characterization of Bone Marrow Mononuclear Cells on Biomaterials
for Bone Tissue Engineering In Vitro".
PMID- 26417592
TI - Intra-Amniotic LPS Induced Region-Specific Changes in Presynaptic Bouton
Densities in the Ovine Fetal Brain.
AB - RATIONALE: Chorioamnionitis has been associated with increased risk for fetal
brain damage. Although, it is now accepted that synaptic dysfunction might be
responsible for functional deficits, synaptic densities/numbers after a fetal
inflammatory challenge have not been studied in different regions yet. Therefore,
we tested in this study the hypothesis that LPS-induced chorioamnionitis caused
profound changes in synaptic densities in different regions of the fetal sheep
brain. MATERIAL AND METHODS: Chorioamnionitis was induced by a 10 mg intra
amniotic LPS injection at two different exposure intervals. The fetal brain was
studied at 125 days of gestation (term = 150 days) either 2 (LPS2D group) or 14
days (LPS14D group) after LPS or saline injection (control group). Synaptophysin
immunohistochemistry was used to quantify the presynaptic density in layers 2-3
and 5-6 of the motor cortex, somatosensory cortex, entorhinal cortex, and
piriforme cortex, in the nucleus caudatus and putamen and in CA1/2, CA3, and
dentate gyrus of the hippocampus. RESULTS: There was a significant reduction in
presynaptic bouton densities in layers 2-3 and 5-6 of the motor cortex and in
layers 2-3 of the entorhinal and the somatosensory cortex, in the nucleus caudate
and putamen and the CA1/2 and CA3 of the hippocampus in the LPS2D compared to
control animals. Only in the motor cortex and putamen, the presynaptic density
was significantly decreased in the LPS14 D compared to the control group. No
changes were found in the dentate gyrus of the hippocampus and the piriforme
cortex. CONCLUSION: We demonstrated that LPS-induced chorioamnionitis caused a
decreased density in presynaptic boutons in different areas in the fetal brain.
These synaptic changes seemed to be region-specific, with some regions being more
affected than others, and seemed to be transient in some regions.
PMID- 26417594
TI - Circulating S100B and Adiponectin in Children Who Underwent Open Heart Surgery
and Cardiopulmonary Bypass.
AB - BACKGROUND: S100B protein, previously proposed as a consolidated marker of brain
damage in congenital heart disease (CHD) newborns who underwent cardiac surgery
and cardiopulmonary bypass (CPB), has been progressively abandoned due to S100B
CNS extra-source such as adipose tissue. The present study investigated CHD
newborns, if adipose tissue contributes significantly to S100B serum levels.
METHODS: We conducted a prospective study in 26 CHD infants, without preexisting
neurological disorders, who underwent cardiac surgery and CPB in whom blood
samples for S100B and adiponectin (ADN) measurement were drawn at five
perioperative time-points. RESULTS: S100B showed a significant increase from
hospital admission up to 24 h after procedure reaching its maximum peak (P <
0.01) during CPB and at the end of the surgical procedure. Moreover, ADN showed a
flat pattern and no significant differences (P > 0.05) have been found all along
perioperative monitoring. ADN/S100B ratio pattern was identical to S100B alone
with the higher peak at the end of CPB and remained higher up to 24 h from
surgery. CONCLUSIONS: The present study provides evidence that, in CHD infants,
S100B protein is not affected by an extra-source adipose tissue release as
suggested by no changes in circulating ADN concentrations.
PMID- 26417596
TI - The Effects of TiO2 Nanodot Films with RGD Immobilization on Light-Induced Cell
Sheet Technology.
AB - Cell sheet technology is a new strategy in tissue engineering which could be
possible to implant into the body without a scaffold. In order to get an
integrated cell sheet, a light-induced method via UV365 is used for cell sheet
detachment from culture dishes. In this study, we investigated the possibility of
cell detachment and growth efficiency on TiO2 nanodot films with RGD
immobilization on light-induced cell sheet technology. Mouse calvaria-derived,
preosteoblastic (MC3T3-E1) cells were cultured on TiO2 nanodot films with (TR) or
without (TN) RGD immobilization. After cells were cultured with or without 5.5
mW/cm(2) UV365 illumination, cell morphology, cell viability, osteogenesis
related RNA and protein expression, and cell detachment ability were compared,
respectively. Light-induced cell detachment was possible when cells were cultured
on TR samples. Also, cells cultured on TR samples showed better cell viability,
alongside higher protein and RNA expression than on TN samples. This study
provides a new biomaterial for light-induced cell/cell sheet harvesting.
PMID- 26417595
TI - Biomarkers of Brain Damage and Postoperative Cognitive Disorders in Orthopedic
Patients: An Update.
AB - The incidence of postoperative cognitive dysfunction (POCD) in orthopedic
patients varies from 16% to 45%, although it can be as high as 72%. As a
consequence, the hospitalization time of patients who developed POCD was longer,
the outcome and quality of life were worsened, and prolonged medical and social
assistance were necessary. In this review the short description of such
biomarkers of brain damage as the S100B protein, NSE, GFAP, Tau protein,
metalloproteinases, ubiquitin C terminal hydrolase, microtubule-associated
protein, myelin basic protein, alpha-II spectrin breakdown products, and microRNA
was made. The role of thromboembolic material in the development of cognitive
decline was also discussed. Special attention was paid to optimization of
surgical and anesthetic procedures in the prevention of postoperative cognitive
decline.
PMID- 26417597
TI - Posterior Cingulate Lactate as a Metabolic Biomarker in Amnestic Mild Cognitive
Impairment.
AB - Mitochondrial dysfunction represents a central factor within the pathogenesis of
the Alzheimer's disease (AD) spectrum. We hypothesized that in vivo measurements
of lactate (lac), a by-product of glycolysis, would correlate with functional
impairment and measures of brain health in a cohort of 15 amnestic mild cognitive
impairment (aMCI) individuals. Lac was quantified from the precuneus/posterior
cingulate (PPC) using 2-dimensional J-resolved magnetic resonance spectroscopy
(MRS). Additionally, standard behavioral and imaging markers of aMCI disease
progression were acquired. PPC lac was negatively correlated with performance on
the Wechsler logical memory tests and on the minimental state examination even
after accounting for gray matter, cerebral spinal fluid volume, and age. No such
relationships were observed between lac and performance on nonmemory tests.
Significant negative relationships were also noted between PPC lac and
hippocampal volume and PPC functional connectivity. Together, these results
reveal that aMCI individuals with a greater disease progression have increased
concentrations of PPC lac. Because lac is upregulated as a compensatory response
to mitochondrial impairment, we propose that J-resolved MRS of lac is a
noninvasive, surrogate biomarker of impaired metabolic function and would provide
a useful means of tracking mitochondrial function during therapeutic trials
targeting brain metabolism.
PMID- 26417598
TI - The Cortisol Awakening Response in Patients with Poststroke Depression Is Blunted
and Negatively Correlated with Depressive Mood.
AB - It is important to reduce poststroke depression (PSD) to improve the stroke
outcomes and quality of life in stroke patients, but the underlying mechanisms of
PSD are not completely understood. As many studies implicate dysregulation of
hypothalamic-pituitary-adrenal axis in the etiology of major depression and
stroke, we compared the cortisol awakening response (CAR) of 28 admitted PSD
patients with that of 23 age-matched caregiver controls. Saliva samples for
cortisol measurement were collected immediately, 15, 30, and 45 min after
awakening for two consecutive days. Depressive mood status in PSD patients was
determined with Beck Depression Inventory and Hamilton Depression Rating Scale.
Salivary cortisol levels of PSD patients did not rise significantly at any
sampling time, showing a somewhat flat curve. Caregiver controls showed
significantly higher CAR at 15 and 30 min after awakening compared to PSD
patients even though the two groups did not differ at awakening or 45 min after
awakening. Area-under-the-curve analysis revealed a significant negative
correlation between the CAR and the degree of depression in PSD patients. Thus,
our findings suggest that poststroke depression is closely related with
dysfunctional HPA axis indicated by blunted CAR.
PMID- 26417599
TI - Sustained Reduction of Cerebellar Activity in Experimental Epilepsy.
AB - Clinical and experimental evidence suggests a role for the cerebellum in seizure
control, while no data are available on cerebellar activity between seizures. We
hypothesized that interictal regional activity of the deep cerebellar nuclei is
reduced in epilepsy and tested this in an animal model by using DeltaFosB and
cytochrome oxidase (COX) (immuno)histochemistry. The expression of these two
markers of neuronal activity was analysed in the dentate nucleus (DN),
interpositus nucleus (IN), and fastigial nucleus (FN) of the cerebellum of fully
amygdala kindled rats that were sacrificed 48 hours after their last seizure. The
DN and FN of kindled rats exhibited 25 to 29% less DeltaFosB immunopositive cells
than their respective counterpart in sham controls (P < 0.05). COX expression in
the DN and FN of kindled animals was reduced by 32 to 33% compared to respective
control values (P < 0.05). These results indicate that an epileptogenic state is
characterized by decreased activity of deep cerebellar nuclei, especially the DN
and FN. Possible consequences may include a decreased activation of the thalamus,
contributing to further seizure spread. Restoration of FN activity by low
frequency electrical stimulation is suggested as a possible treatment option in
chronic epilepsy.
PMID- 26417600
TI - Role and Importance of IGF-1 in Traumatic Brain Injuries.
AB - It is increasingly affirmed that most of the long-term consequences of TBI are
due to molecular and cellular changes occurring during the acute phase of the
injury and which may, afterwards, persist or progress. Understanding how to
prevent secondary damage and improve outcome in trauma patients, has been always
a target of scientific interest. Plans of studies focused their attention on the
posttraumatic neuroendocrine dysfunction in order to achieve a correlation
between hormone blood level and TBI outcomes. The somatotropic axis (GH and IGF
1) seems to be the most affected, with different alterations between the acute
and late phases. IGF-1 plays an important role in brain growth and development,
and it is related to repair responses to damage for both the central and
peripheral nervous system. The IGF-1 blood levels result prone to decrease during
both the early and late phases after TBI. Despite this, experimental studies on
animals have shown that the CNS responds to the injury upregulating the
expression of IGF-1; thus it appears to be related to the secondary mechanisms of
response to posttraumatic damage. We review the mechanisms involving IGF-1 in
TBI, analyzing how its expression and metabolism may affect prognosis and outcome
in head trauma patients.
PMID- 26417602
TI - Quantitative Anatomical Studies.
PMID- 26417601
TI - Regeneration, Plasticity, and Induced Molecular Programs in Adult Zebrafish
Brain.
AB - Regenerative capacity of the brain is a variable trait within animals. Aquatic
vertebrates such as zebrafish have widespread ability to renew their brains upon
damage, while mammals have--if not none--very limited overall regenerative
competence. Underlying cause of such a disparity is not fully evident; however,
one of the reasons could be activation of peculiar molecular programs, which
might have specific roles after injury or damage, by the organisms that
regenerate. If this hypothesis is correct, then there must be genes and pathways
that (a) are expressed only after injury or damage in tissues, (b) are
biologically and functionally relevant to restoration of neural tissue, and (c)
are not detected in regenerating organisms. Presence of such programs might
circumvent the initial detrimental effects of the damage and subsequently set up
the stage for tissue redevelopment to take place by modulating the plasticity of
the neural stem/progenitor cells. Additionally, if transferable, those "molecular
mechanisms of regeneration" could open up new avenues for regenerative therapies
of humans in clinical settings. This review focuses on the recent studies
addressing injury/damage-induced molecular programs in zebrafish brain,
underscoring the possibility of the presence of genes that could be used as
biomarkers of neural plasticity and regeneration.
PMID- 26417603
TI - Fascioliasis: An Ongoing Zoonotic Trematode Infection.
AB - Zoonotic trematode infections are an area of the neglected tropical diseases that
have become of major interest to global and public health due to their associated
morbidity. Human fascioliasis is a trematode zoonosis of interest in public
health. It affects approximately 50 million people worldwide and over 180 million
are at risk of infection in both developed and underdeveloped countries. The one
health paradigm is an area that seeks to address the problem of zoonotic
infections through a comprehensive and sustainable approach. This review attempts
to address the major challenges in managing human and animal fascioliasis with
valuable insights gained from the one health paradigm to global health and
multidisciplinary integration.
PMID- 26417604
TI - Gray and White Matter Volumes and Cognitive Dysfunction in Drug-Naive Newly
Diagnosed Pediatric Epilepsy.
AB - Epilepsy patients often have cognitive dysfunction even at early stages of
disease. We investigated the relationship between structural findings and
neuropsychological status in drug-naive newly diagnosed pediatric epilepsy
patients. Thirty newly diagnosed pediatric epilepsy patients and 25 healthy
control subjects aged 7~16 years were enrolled, who were assessed by the Korean
version of the Wechsler Intelligence Scale for Children (K-WISC-III), the Stroop
test, and the trail making test (TMT). Optimized voxel-based morphometry (VBM)
was performed for both Gray Matter (GM) and White Matter (WM) volumes. Lower
performance levels of verbal intelligence quotient, freedom from distractibility,
and executive function were observed in epilepsy group. Interestingly, poor
performance in these cognitive subdomains was correlated with regional VBM
findings involving both GM and WM volumes, but with different patterns between
groups. GM volumes revealed clear differences predominantly in the bilateral
frontal regions. These findings indicate that certain cognitive functions may be
affected in the early stage of epilepsy, not related to the long-standing
epilepsy or medication, but more related to the neurocognitive developmental
process in this age. Epilepsy can lead to neuroanatomical alterations in both GM
and WM, which may affect cognitive functions, during early stages even before
commencement of AED medication.
PMID- 26417605
TI - Mutations Found in embCAB, embR, and ubiA Genes of Ethambutol-Sensitive and
Resistant Mycobacterium tuberculosis Clinical Isolates from China.
AB - To better understand the molecular mechanisms of Ethambutol (EMB) resistance, the
mutant hot spot region of five genes (embB, embA, embC, embR, and ubiA) was
amplified and sequenced in 109 EMB-resistant and 153 EMB-susceptible clinical
isolates from China. Twenty-seven EMB-susceptible isolates were found to have
nonsynonym mutations, 23 of which were in embB. The mutations occurred most
frequently in embB (85.3%, 93) and were seldom in embC (2.8%, 3), embA (3.7%, 4),
embR (3.7%, 4), and ubiA (8.3%, 9) in EMB-resistant isolates. For the embB gene,
63 isolates showed mutations at embB306, 20 at embB406, nine at embB497, and five
at embB354 in EMB-resistant isolates. In addition, the particular mutants at
embB406 and embB497 indicated both high levels of EMB resistance (MICs > 5
MUg/mL) and broad anti-TB drug resistance spectrums. Our data supported the facts
that embB306 could be used as a marker for EMB resistance with a sensitivity of
57.8% and a specificity of 78.8%.
PMID- 26417607
TI - Food Service Perspectives on National School Lunch Program Implementation.
AB - OBJECTIVES: Explore barriers and facilitators to implementation of the new
National School Lunch Program (NSLP) policy guidelines. METHODS: Interviews with
eight food service directors using an interview guide informed by the
Consolidated Framework for Implementation Research. RESULTS: Food service
personnel; parents, teachers, school staff; and students were important
stakeholders. Characteristics of the new NSLP policy guidelines were reported to
create increased demands; resources alleviated some barriers. Directors reported
increased food and labor costs, food sourcing challenges, decreased student
participation, and organizational constraints as barriers to implementation.
Creativity in menu planning facilitated success. CONCLUSIONS: Factors within the
food service department, characteristics of implementing individuals and the new
NSLP policy guidelines, and stakeholder involvement in the implementation process
relate to successful implementation.
PMID- 26417606
TI - The Bidirectional Relationship between Sleep and Immunity against Infections.
AB - Sleep is considered an important modulator of the immune response. Thus, a lack
of sleep can weaken immunity, increasing organism susceptibility to infection.
For instance, shorter sleep durations are associated with a rise in suffering
from the common cold. The function of sleep in altering immune responses must be
determined to understand how sleep deprivation increases the susceptibility to
viral, bacterial, and parasitic infections. There are several explanations for
greater susceptibility to infections after reduced sleep, such as impaired
mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the
upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have
been observed during partial sleep deprivation. Also, steroid hormones, in
addition to regulating sexual behavior, influence sleep. Thus, we hypothesize
that sleep and the immune-endocrine system have a bidirectional relationship in
governing various physiological processes, including immunity to infections. This
review discusses the evidence on the bidirectional effects of the immune response
against viral, bacterial, and parasitic infections on sleep patterns and how the
lack of sleep affects the immune response against such agents. Because sleep is
essential in the maintenance of homeostasis, these situations must be adapted to
elicit changes in sleep patterns and other physiological parameters during the
immune response to infections to which the organism is continuously exposed.
PMID- 26417608
TI - Quantitative high-throughput gene expression profiling of human striatal
development to screen stem cell-derived medium spiny neurons.
AB - A systematic characterization of the spatio-temporal gene expression during human
neurodevelopment is essential to understand brain function in both physiological
and pathological conditions. In recent years, stem cell technology has provided
an in vitro tool to recapitulate human development, permitting also the
generation of human models for many diseases. The correct differentiation of
human pluripotent stem cell (hPSC) into specific cell types should be evaluated
by comparison with specific cells/tissue profiles from the equivalent adult in
vivo organ. Here, we define by a quantitative high-throughput gene expression
analysis the subset of specific genes of the whole ganglionic eminence (WGE) and
adult human striatum. Our results demonstrate that not only the number of
specific genes is crucial but also their relative expression levels between brain
areas. We next used these gene profiles to characterize the differentiation of
hPSCs. Our findings demonstrate a temporal progression of gene expression during
striatal differentiation of hPSCs from a WGE toward an adult striatum identity.
Present results establish a gene expression profile to qualitatively and
quantitatively evaluate the telencephalic hPSC-derived progenitors eventually
used for transplantation and mature striatal neurons for disease modeling and
drug-screening.
PMID- 26417609
TI - A marker-free system for highly efficient construction of vaccinia virus vectors
using CRISPR Cas9.
AB - The current method for creation of vaccinia virus (VACV) vectors involves using a
selection and purification marker, however inclusion of a gene without
therapeutic value in the resulting vector is not desirable for clinical use. The
Cre-LoxP system has been used to make marker-free Poxviruses, but the efficiency
was very low. To obtain a marker-free VACV vector, we developed marker gene
excision systems to modify the thymidine kinase (TK) region and N1L regions using
Cre-Loxp and Flp-FRET systems respectively. CRISPR-Cas9 system significantly
resulted in a high efficiency (~90%) in generation of marker gene-positive TK
mutant VACV vector. The marker gene (RFP) could be excised from the recombinant
virus using Cre recombinase. To make a marker-free VV vector with double gene
deletions targeting the TK and N1L gene, we constructed a donor repair vector
targeting the N1L gene, which can carry a therapeutic gene and the marker (RFP)
that could be excised from the recombinant virus using Flp recombinase. The
marker-free system developed here can be used to efficiently construct VACV
vectors armed with any therapeutic genes in the TK region or N1L region without
marker genes. Our marker-free system platform has significant potential for
development of new marker-free VACV vectors for clinical application.
PMID- 26417610
TI - Inhibitory Control is Associated with Psychosocial, Cognitive, and Weight
Outcomes in a Longitudinal Sample of Girls.
AB - Early self-regulation abilities have been highlighted as a robust predictor of
adaptive development, but the extant literature has typically focused on outcomes
in different developmental domains separately. The aim of the current study was
to expand upon this research by testing pathways from girls' inhibitory control
at age 7, an aspect of self-regulation, to their psychosocial, cognitive, and
weight outcomes from ages 9 to 15 (n=192). Results supported the hypothesis that
greater inhibitory control is independently associated with better subsequent
psychosocial, cognitive, and weight outcomes. These findings, combined with
evidence that self-regulatory capacities are modifiable in early childhood, offer
opportunities for interdisciplinary preventive interventions aiming to promote
child health and well-being across domains and over time.
PMID- 26417611
TI - Developments in Neurovascular Diseases and Treatments.
PMID- 26417613
TI - Possible association between mandibular repositioning device for sleep apnea and
osseous lytic lesion with fracture of the coronoid process of the mandible: A
case report.
AB - Mandibular repositioning devices (MRDs) increase the patency of the upper airway
by repositioning the mandible forward, resulting in displacement of the
oropharyngeal tissues preventing upper airway collapsibility. Mandibular anterior
repositioning is counteracted by muscle force from the temporalis muscle. A 39
year-old man had an osteolytic lesion with fracture of the coronoid process of
the mandible secondary to wearing a MRD for sleep apnea. Continuous stress
generated on the coronoid process temporalis muscle resulted in osteolysis and
fracture of the coronoid process on the patient's right side, resulting in
swelling and limited ability to open his mouth. The patient was managed with
intravenous antibiotics to control the osteomyelitis and surgical debridement,
with removal of the coronoid process of the mandible. It is unclear why the
fracture only occurred on the right side. Pathologic fracture of the coronoid
process due to chronic stress and secondary osteomyelitis is a rare severe
complication of treatment for obstructive sleep apnea syndrome with a MRD.
PMID- 26417614
TI - A rare case of a broken dental bur perforating the medial orbital wall without
damaging the eye.
AB - Rotating instruments used in the fields of dentistry and oral surgery operate at
high speeds. Therefore, if small particles are projected and strike the orbit,
injuries of varying severity can occur. We report here a case in which a broken
dental bur pierced into the orbit. The bur fortunately did not damage the eyeball
and stopped after penetration of the medial orbital wall. The subject was a 27
year-old dental assistant and not wearing protective eyewear. A foreign body had
penetrated the medial wall of the right orbit and the tip had reached the ethmoid
sinus. The medial orbital wall was exposed subperiosteally after dissection of
the medial canthal ligament, and the foreign body was removed. Although the
importance of protective eyewear had been advocated, eye protection compliance
differed by region and dental personnel. Eye protection use needs to increase in
not only dentists but also other dental personnel.
PMID- 26417615
TI - Evaluation of root canal configuration of maxillary and mandibular anterior teeth
using cone beam computed tomography: An in-vivo study.
AB - OBJECTIVE: Several studies demonstrate variability of root canal morphology of
anterior teeth. This in-vivo study was designed to analyze and characterize root
canal morphology of maxillary and mandibular anterior teeth using three
dimensional imaging. METHOD AND MATERIALS: Patients who required CBCT
radiographic examinations as part of their routine examination, diagnosis, and
treatment planning were enrolled on the study. A total of 1,200 healthy,
untreated, fully developed maxillary and mandibular incisors and canines were
included. The following observations were recorded: (i) number of roots and their
morphology; (ii) number of canals per root; and (iii) primary variations in the
morphology of the root canal systems. RESULTS: Root canal morphology of maxillary
teeth was consistent with a single canal extending from the pulp chamber to the
apex in 98% of the cases. In contrast, in mandibular central and lateral
incisors, the presence of a single canal represented 64.5% and 60.5%
respectively. The second most common morphology was the presence of one canal
leaving the pulp chamber, which divided into two within the root, and then merged
to exit as one canal in 18% and 25.5% respectively. The presence of one canal
leaving the pulp chamber and dividing short of the apex into two separate and
distinct canals with separate apical foramina (variant 5) was recorded in 14.5%
and 12% respectively. CONCLUSION: There was a low incidence of anatomical
variation in maxillary anterior teeth. In contrast, mandibular anterior teeth
presented with a high prevalence of two canals, especially central and lateral
incisors. The reported data may help clinicians understand the variations in root
canal morphology of anterior teeth in order to overcome problems associated with
shaping and cleaning procedures.
PMID- 26417612
TI - Inflammatory Signaling Involved in High-Fat Diet Induced Prostate Diseases.
AB - High-Fat Diet (HFD) has emerged as an important risk factor not only for obesity
and diabetes but also for urological disorders. Recent research provides ample
evidence that HFD is a putative cause for prostatic diseases including prostate
cancer. The mechanisms whereby these diseases develop in the prostate have not
been fully elucidated. In this review we discuss signaling pathways intricately
involved in HFD-induced prostate disease. We performed a search through PUBMED
using key words "high fat diet" and "prostate". Our data and perspectives are
included in this review along with research performed by various other groups.
HFD is positively associated with an increased risk of benign prostatic
hyperplasia (BPH) and prostate cancer. HFD induces oxidative stress and
inflammation in the prostate gland, and these adverse influences transform it
from a normal to a diseased state. Studies demonstrate that HFD accelerates the
generation of reactive oxygen species by driving the NADPH oxidase system,
exacerbating oxidative stress in the prostate. HFD also causes a significant
increase in the levels of pro-inflammatory cytokines and gene products through
activation of two important signaling pathways: the Signal Transducer and
Activator of Transcription (STAT)-3 and Nuclear Factor-kappa B (NF-kappaB). Both
these pathways function as transcription factors required for regulating genes
involved in proliferation, survival, angiogenesis, invasion and inflammation. The
crosstalk between these two pathways enhances their regulatory function. Through
its influences on the NF-kappaB and Stat-3 signaling pathways, it appears likely
that HFD increases the risk of development of BPH and prostate cancer.
PMID- 26417616
TI - Full-mouth rehabilitation with monolithic CAD/CAM-fabricated hybrid and all
ceramic materials: A case report and 3-year follow up.
AB - Esthetic full-mouth rehabilitation represents a great challenge for clinicians
and dental technicians. Computer-aided design/ computer-assisted manufacture
(CAD/CAM) technology and novel ceramic materials in combination with adhesive
cementation provide a reliable, predictable, and economic workflow. Polychromatic
feldspathic CAD/CAM ceramics that are specifically designed for anterior
indications result in superior esthetics, whereas novel CAD/CAM hybrid ceramics
provide sufficient fracture resistance and adsorption of the occlusal load in
posterior areas. Screw-retained monolithic CAD/CAM lithium disilicate crowns (ie,
hybrid abutment crowns) represent a reliable and time- and cost-efficient
prosthetic implant solution. This case report details a CAD/CAM approach to the
full-arch rehabilitation of a 65-year-old patient with toothand implant-supported
restorations and provides an overview of the applied CAD/CAM materials and the
utilized chairside intraoral scanner. The esthetics, functional occlusion, and
gingival and peri-implant tissues remained stable over a follow-up period of 3
years. No signs of fractures within the restorations were observed.
PMID- 26417617
TI - Partial-prep bonded restorations in the anterior dentition: Long-term gingival
health and predictability. A case report.
AB - Bonded porcelain restorations are a predictable and durable treatment option that
can restore not only the strength and function of the teeth but also the esthetic
appearance. One important issue in adhesive dentistry is the preservation of
sound enamel. Following biomimetic principles, employing minimally invasive
applications and adhesive technologies is of paramount importance for successful
restorations. While it is widely accepted that minimally invasive restorative
techniques should be favored, there is still some controversy over the
noninvasive approaches. The purpose of this article is to question the complete
"no-prep veneer" concept due to the possible negative effects on periodontal
health caused by excessive contour and overhangs of the ceramic restoration, and
to propose a new method to assess the quality and longevity of veneers with a
partial-prep concept.
PMID- 26417618
TI - The association between dental proximal restorations and periodontal disease: A
retrospective 10-18 years longitudinal study.
AB - OBJECTIVE: Dental restorations may be plaque retentive. The aim of this study was
to evaluate the long-term association between proximal restorations and the
incidence and progression of periodontal disease in well-maintained patients.
METHOD AND MATERIALS: Probing pocket depths (PPD), bleeding on probing (BOP), and
radiographic status of proximal restorations were retrospectively retrieved from
files of patients attending a specialist periodontal office. Ill-fitting margins
were recorded. The association between these parameters was evaluated at baseline
examination (T0), after cause-related therapy (T1) and after >= 10 years from T0
(T2), during which supportive periodontal therapy (SPT) was administered, using
descriptive statistics, ANOVA-Bonferroni, and chi-square analyses. RESULTS: 1,301
teeth were examined. Mean PPD in unrestored surfaces was 3.7 +/- 1.7 mm, 3.1 +/-
1.3 mm, and 2.8 +/- 1 mm at T0, T1, and T2, respectively. Deeper pockets were
found in restored surfaces at those time points with PPD values of 4.4 +/- 1.8
mm, 3.6 +/- 1.4 mm, and 3.2 +/- 1.1 mm, respectively (P < .001). Higher PPD
values were found in restored surfaces exhibiting inadequate restorations when
compared to restored surfaces with adequate restorations at all time points.
These values were 4.9 +/- 1.9 mm, 4.1 +/- 1.5 mm, and 4 +/- 1.7 mm vs 4.3 +/- 1.8
mm, 3.6 +/- 1.4 mm, and 3.1 +/- 1.1 mm, respectively (P < .001). CONCLUSION: The
present study confirmed that restorations might be detrimental to periodontal
health. A significant association between the presence of proximal restorations
and the incidence of periodontal disease was observed. This association was more
pronounced for inadequate restorations while becoming less significant over time
in patients receiving routine SPT.
PMID- 26417619
TI - Effect of full-mouth disinfection on insulin sensitivity in type 2 diabetes
patients with and without chronic periodontitis.
AB - OBJECTIVE: To explore the effect of full-mouth disinfection (FMD) on glycemic
control and insulin resistance in type 2 diabetes mellitus (DM). METHOD AND
MATERIALS: Sixty dentate patients who were never-smokers with type 2 diabetes
mellitus were recruited for the study. Based on clinical examination they were
divided into two groups: one with chronic periodontitis and the other without
chronic periodontitis. Periodontal parameters Plaque Index (PI), Gingival Index
(GI), and probing pocket depth (PPD) were evaluated. Blood samples were assessed
for the levels of fasting glucose (FG), insulin, and C-reactive protein (CRP),
and insulin glucose ratio was calculated using a mathematical equation (HOMA-IR).
All parameters were assessed at baseline, and at 3 months and 6 months after FMD.
RESULTS: The results showed a significant reduction in PI, GI, PPD, FG, and HOMA
IR from baseline to 6 months. The CRP levels were constant throughout the study
period. CONCLUSION: Within the limitations of the present study it can be
concluded that FMD contributes to significant reduction in insulin resistance,
thereby improving the glycemic control in type 2 diabetes mellitus patients.
PMID- 26417621
TI - Very late recurrence of renal cell carcinoma experiencing long-term response to
sunitinib: a case report.
AB - Renal cell carcinoma (RCC) is responsible for 4% of all neoplasms in adults and
for 80% of all primary renal tumors. Metastatic RCC is resistant to all cytotoxic
agents and generally prognosis is poor. However, the clinical behavior of RCC is
unpredictable, and late recurrences of disease can occur even after several years
from the initial surgical approach, so response to the currently available
targeted agents is uncertain, due to the lack of reliable prognostic and
predictive factors. We report the case of a patient who developed a metastatic
recurrence of RCC 16 years after primary treatment, in spite of metastatic
disease at diagnosis. At the time of relapse, the disease showed a surprisingly
long-term response to Sunitinib, which is maintained after 74 months of
treatment. This case report highlights the unpredictable behavior of RCC and
underlines the presence of a subset of patients with metastatic RCC achieving
long-term response to Sunitinib, despite poor clinical features. In this subset
of patients, an important clinical question arises about the appropriate duration
of treatment and the need to continue it indefinitely.
PMID- 26417622
TI - Setting Expectations.
PMID- 26417623
TI - Alcohol, Tobacco, Triggers, and Headache Disorders.
PMID- 26417624
TI - Oral contraceptives: a good scare.
PMID- 26417625
TI - Bevacizumab (AVASTIN) and age-related macular degeneration. Lower cost does not
justify taking risks.
AB - Intravitreal injection of ranibizumab, a VEGF inhibitor, is an option for
patients with neovascular age-related macular degeneration (AMD). Because of its
lower price, bevacizumab, a VEGF inhibitor closely related to ranibizumab and
marketed for the treatment of various malignancies, is sometimes used off label
for intravitreal injection in AMD. In 2011, the harm-benefit balance of
bevacizumab in patients with AMD was uncertain. New data are available in 2015.
In six randomised trials including a total of about 3200 patients, funded
independently of the pharmaceutical industry, bevacizumab (1.25 mg per dose) was
about as effective as ranibizumab (0.5 mg per injection): visual acuity
stabilised or improved in 90% to 95% of patients after one to two years of
treatment. During these trials, bevacizumab did not reduce the number of
injections needed, as compared with ranibizumab. These trials confirmed the known
adverse effect profile of bevacizumab, which is similar to that of ranibizumab
and includes serious ocular as well as extraocular adverse effects, in particular
cardiac disorders. Serious extraocular adverse events, especially
gastrointestinal disorders, were more frequent with bevacizumab than with
ranibizumab at one year (18% versus 14%). In early 2015, there are no bevacizumab
products suitable for intravitreal injection. In 2011, cases of sight-threatening
infectious endophthalmitis were reported in the United States, following
contamination during syringe preparation for intravitreal administration. In
practice, when treatment with a VEGF inhibitor is considered for AMD, it is more
prudent to choose ranibizumab, despite its currently unacceptable price.
PMID- 26417627
TI - Apixaban (Eliquis) in deep vein thrombosis and pulmonary embolism. Warfarin
remains the standard therapy.
AB - Not more effective than warfarin. The lower incidence of bleeding observed among
patients selected for these trials must be weighed against the lack of either an
antidote or a routine clotting test.
PMID- 26417626
TI - Ranibizumab: reject such high (exorbitant) prices.
PMID- 26417628
TI - Aflibercept (Eylea) and diabetic macular oedema. A first-choice VEGF inhibitor in
case of marked visual loss.
AB - Overall, VEGF inhibitors administered by intravitreal injection have a similar
harm-benefit balance. However, a publicly funded trial has shown that aflibercept
is more effective than ranibizumab and bevacizumab in patients with marked loss
of visual acuity.
PMID- 26417629
TI - Eltrombopag (Revolade ) and thrombocytopenia in patients with hepatitis C.
Hepatotoxic drug; more harms than benefits.
AB - Too many potentially life-threatening adverse effects, including hepatic
decompensation and thromboembolic complications.
PMID- 26417630
TI - INN common-stem: -olol.
PMID- 26417631
TI - Drug-induced lesions of the oesophageal mucosa.
AB - Lesions of the oesophageal mucosa are observed in various situations: most often
with gastrooesophageal reflux disease, but also with infections, cancer, contact
with a toxic substance, etc. When they are symptomatic, these lesions provoke
burning sensations, dysphagia, regurgitation and sometimes dorsal pain. The
changes to the oesophageal mucosa may take various forms: inflammation, erosion,
ulceration or necrosis. Serious or even fatal complications can develop but are
rare; they include oesophageal perforation, stricture and haemorrhage. Some oral
drugs damage the oesophageal mucosa through direct contact. The symptoms often
develop several hours after ingestion. The pain is of sudden onset. The resulting
lesions are solitary or multiple ulcers that vary in depth and usually occur in
the upper portion of the oesophagus. Various factors prolong contact between a
drug and the oesophageal mucosa, in particular: swallowing the drug with
insufficient liquid or just before lying down; capsule forms; and oesophageal
abnormalities. The drugs most frequently implicated are tetracyclines,
particularly doxycycline, bisphosphonates and various nonsteroidal anti
inflammatory drugs (NSAIDs). Many drugs, used in various situations, provoke
gastro-oesophageal reflux disease, sometimes causing mucosal lesions in the lower
oesophagus: calcium-channel blockers, nitrates, exenatide and liraglutide, drugs
with antimuscarinic effects, theophylline, etc. Some drugs affect all mucous
membranes in the body, including the oesophageal mucosa, irrespective of their
route of administration: cancer drugs, isotretinoin, and nicorandil.
PMID- 26417632
TI - Lesions of the oesophageal mucosa and their causes.
PMID- 26417633
TI - Baclofen and pregnancy: birth defects and withdrawal symptoms.
AB - A comparison of 134 pregnant women who had taken baclofen in early pregnancy and
400 pregnant controls showed an increased risk of major malformations. Several
infants exposed to baclofen until birth exhibited withdrawal symptoms.
PMID- 26417634
TI - Parkinson's disease: initial treatment of motor disorders.
AB - Parkinson's disease is characterised by three main symptoms: slowness and paucity
of movements, rigidity, and resting tremor. Rapid improvement in these symptoms
after levodopa administration supports the diagnosis of Parkinson's disease. It
is important to inform the patient tactfully, allowing him or her to control the
pace at which information on the diagnosis, symptoms and prognosis is conveyed.
Patients with minimal discomfort or mild disability derive little benefit from
drug therapy. Physiotherapy and physical exercises are sometimes useful.
Previously untreated patients with marked functional impairment should receive
medication. The choice is essentially between levodopa and ropinirole, and mainly
depends on the patient's age.
PMID- 26417635
TI - Prevention of deep vein thrombosis. First choice treatments.
PMID- 26417636
TI - Breast cancer and duration of tamoxifen.
AB - Two randomised trials have compared 5 years versus 10 years of tamoxifen therapy
following surgery for hormone receptor-positive early breast cancer. Overall
mortality, breast cancer-related mortality and the breast cancer recurrence rate
were all lower when tamoxifen was continued for 10 years. Prolonging tamoxifen
therapy increased the incidence of endometrial cancer and thromboembolic events.
The value of tamoxifen therapy therefore decreases over time.
PMID- 26417637
TI - Type 2 diabetes: Mediterranean diet delays need for drug therapy.
AB - According to a trial in patients with recently diagnosed type 2 diabetes,
adopting a "Mediterranean" diet seems to delay the need for glucose-lowering
drugs by several years compared with a low-fat diet.
PMID- 26417638
TI - Ischaemic stroke: decide rapidly.
AB - A meta-analysis of individual data for 6756 patients showed that intravenous
thrombolysis with alteplase improved survival without overt neurological deficits
when started within 4.5 hours of the first symptoms of ischaemic stroke, at a
cost of increased mortality due to cerebral haemorrhage during the week following
thrombolysis.
PMID- 26417639
TI - Discounted drug prices for hospitals: result in prescriptions for expensive drugs
in the community.
AB - Hospital prescribing has a major influence on community prescribing. In France,
pharmaceutical companies can sell drugs to hospitals at dramatically reduced
prices in the expectation of increasing sales in community pharmacies.
PMID- 26417640
TI - Microphthalmia-associated transcription factor mutations are associated with
white-spotted coat color in swamp buffalo.
AB - A candidate gene analysis of the microphthalmia-associated transcription factor
(MITF) gene was used in an attempt to identify the genetic basis for a white
spotted coat color phenotype in the Asian swamp buffalo (Bubalus bubalis
carabanensis). Ninety-three buffaloes-32 solid, 38 spotted and 23 white
individuals-were Sanger-sequenced for all MITF exons as well as highly conserved
intronic and flanking regions. MITF cDNA representing skin and iris tissue from
six spotted, nine solid and one white buffaloes was also Sanger-sequenced to
confirm detected mutations. Two independent loss-of-function mutations, a
premature stop codon (c.328C>T, p.Arg110*) and a donor splice-site mutation
(c.840+2T>A, p.Glu281_Leu282Ins8), both of which cause white-spotted coat color
in swamp buffaloes, were identified. The nonsense mutation leads to a premature
stop codon in exon 3, and likely removal of the resulting mRNA via nonsense
mediated decay pathway, whereas the donor splice-site mutation leads to aberrant
splicing of exon 8 that encodes part of a highly conserved region of MITF. The
resulting insertion of eight amino acid residues is expected to perturb the
leucine zipper part in the basic helix-loop-helix leucine zipper (bHLH-Zip)
domain and will most likely influence dimerization and DNA binding capacity.
Electrophoretic mobility shift assay was performed using mutant and wild-type
MITF proteins and showed that the mutant MITF protein resulting from the splice
site mutation decreased in vitro DNA binding capacity compared to wild-type MITF.
White-spotted buffalo bulls are sacrificed in funeral ceremonies in Tana Toraja,
Indonesia, because they are considered holy, and our results show that genetic
variation causes a tie to the cultural use of these buffaloes.
PMID- 26417641
TI - Phase unwrapping in 4D MR flow with a 4D single-step laplacian algorithm.
AB - PURPOSE: To introduce and demonstrate a method for unwrapping 4D flow data by
utilizing continuity constraints in all four available dimensions. MATERIALS AND
METHODS: A Laplacian-based algorithm for unwrapping phase data was expanded to
unwrap along the temporal dimension in addition to all three spatial dimensions.
The method was tested on simulated blood flow under varying vessel diameters and
velocity encoding (Venc ) values. The algorithm was also tested in the aorta of
five volunteers, with wrapped data acquired with Venc = 80 cm/s and 40 cm/s.
Unwrapping performance was measured visually and in comparison to a high Venc
reference free of phase wrapping. Ten patients with aortic coarctations with
clinical Venc values and lower-Venc reconstructions were corrected and scored by
blinded reviewers on a 0-3 scale. RESULTS: Simulated data were completely
unwrapped for most clinically relevant levels of velocity aliasing using the
proposed method. In vivo data in the aorta were completely unwrapped for cases of
moderate wrapping (Venc = 80 cm/s, peak velocities = ~160 cm/s), while residual
aliasing remained for the more considerably aliased datasets (Venc = 40 cm/s).
Improvements were seen in scoring (mean score improved by 1.1 and 2.2 for
clinical and low-Venc datasets, respectively) by the blinded reviewers in the
patient cohort for both standard and low-Venc reconstructions. CONCLUSION: A
computationally fast, fully automated, easy to use, and parameter-free single
step method for unwrapping 4D flow data is shown to be effective for use in most
common clinical occurrences of velocity aliasing.
PMID- 26417642
TI - Surgical Salvage of Thermal Ablation Failures for Renal Cell Carcinoma.
AB - PURPOSE: Cryoablation and radio frequency ablation are attractive modalities for
small renal masses in patients with substantial comorbidities. However, salvage
extirpative therapy for local recurrence after thermal ablation can be
challenging due to associated perinephric fibrosis. MATERIALS AND METHODS:
Patients with thermal ablation refractory tumors requiring surgical salvage from
1997 to 2013 were identified and retrospectively reviewed. RESULTS: A total of 27
patients were treated surgically after cryoablation (18) or radio frequency
ablation (9) failed. Subjective assessment indicated moderate/severe fibrosis in
22 cases (81%). Partial nephrectomy was preferred in all patients but was not
possible in 12, primarily due to unfavorable tumor size/location. In the intended
partial nephrectomy group (15) open surgery was performed in all patients and
completed in 14, with the procedure aborted in 1 due to extensive perinephric
fibrosis. Radical nephrectomy was planned in 12 patients, of whom 8 were treated
laparoscopically with 1 requiring conversion to open. Median estimated blood loss
was 225 ml. Overall 17 patients experienced no complications and 4 had minor
complications. However, 6 patients experienced more significant complications
(Clavien III-IVb). Since January 2008 partial nephrectomy was performed more
frequently (12 of 17, or 71% vs 2 of 10, or 20% for previous cases, p=0.02).
CONCLUSIONS: Surgical salvage after failed thermal ablation is feasible in most
instances, and partial nephrectomy is often possible but can be challenging due
to associated perinephric fibrosis. The difficulty of surgical salvage should be
recognized as a potential limitation of the thermal ablation treatment strategy.
Prospective studies of thermal ablation vs partial nephrectomy should be
prioritized to provide higher quality data about the merits and limitations of
each approach.
PMID- 26417643
TI - Quantitative Proteomic Analysis of Differentially Expressed Proteins and
Downstream Signaling Pathways in Chronic Bladder Ischemia.
AB - PURPOSE: Growing evidence suggests that ischemia may contribute to aging
associated bladder dysfunction and lower urinary tract symptoms. Our goal was to
determine the effects of chronic ischemia on bladder proteomic profiles and
characterize downstream signaling pathways. MATERIALS AND METHODS: Bilateral
iliac artery atherosclerosis and chronic bladder ischemia were created in male
Sprague Dawley(r) rats. At 8 weeks cystometrograms were obtained. Ischemic and
control bladder tissues were then processed for label-free quantitative proteomic
analysis. GO (Gene Ontology) and IPA (Ingenuity(r) Pathway Analysis) software
were used to classify altered proteins in bladder ischemia. Western blot was done
to confirm differentially expressed proteins. Tissue structure was examined by
transmission electron microscopy. RESULTS: Chronic ischemia resulted in detrusor
instability and noncompliance. Proteomic analysis revealed a total of 4,277
proteins in ischemic and 4,602 in control bladder tissues. In ischemic bladders
359 and 66 proteins were differentially expressed with a greater than twofold and
fivefold change, respectively. On GO analysis differentially expressed proteins
were associated with molecular signaling mechanisms underlying proteolysis and
degenerative processes. Pathway and network analysis of ischemic tissues
suggested that altered proteins are involved in ubiquitination, Nrf2 mediated
oxidative stress response, cell death, glucose metabolism and cytoskeleton
remodeling. Western blot verified changes in 4 representative proteins, including
Nedd4l, Mpo, Ca3 and Fkbp5. Altered proteomic profile of the bladder was
associated with widespread ultrastructural damage. CONCLUSIONS: Alterations of
bladder proteomic profiles in ischemia may provide new insight into molecular
pathways underlying bladder dysfunction and lower urinary tract symptoms in
pelvic atherosclerosis.
PMID- 26417645
TI - Renal Vascular Clamp Placement: A Potential Cause of Incomplete Hilar Control
during Partial Nephrectomy.
AB - PURPOSE: Previous benchtop studies have shown that robotic bulldog clamps provide
incomplete vascular control of a Penrose drain. We determined the efficacy of
robotic and laparoscopic bulldog clamps to ensure hemostasis on the human renal
artery. The effect of clamp position on vascular control was also examined.
MATERIALS AND METHODS: Fresh human cadaveric renal arteries were used to
determine the leak point pressure of 7 bulldog clamps from a total of 3
manufacturers. Five trials were performed per clamp at 4 locations, including the
fulcrum, proximal, middle and distal positions. Comparison was done using the
Kruskal-Wallis test with p <0.05 considered significant. RESULTS: None of the
bulldog clamps leaked at a pressure less than 215 mm Hg when applied at the
proximal, middle or distal position. In general leak point pressure decreased as
the artery was positioned more distal along the clamp. The exception was when the
vessel was placed at the fulcrum position. At that position 80% to 100% of trials
with the Klein laparoscopic, 100% with the Klein robotic (Klein Robotic, San
Antonio, Texas) and 60% to 80% with the Scanlan robotic (Scanlan International,
Saint Paul, Minnesota) clamp leaked at pressure below 215 mm Hg. CONCLUSIONS:
Each vascular clamp adequately occluded flow at physiological pressure when
placed at the proximal, middle or distal position. Furthermore, these results
demonstrate that there is leakage at physiological pressure when the artery is
placed at the fulcrum of certain clamp types. These results suggest that applying
a bulldog clamp at the fulcrum could potentially lead to inadequate vessel
occlusion and intraoperative bleeding.
PMID- 26417644
TI - Perirenal Fat Promotes Renal Arterial Endothelial Dysfunction in Obese Swine
through Tumor Necrosis Factor-alpha.
AB - PURPOSE: Perirenal fat is associated with poor blood pressure control and chronic
kidney disease but the underlying mechanisms remain elusive. We tested the
hypothesis that perirenal fat impairs renal arterial endothelial function in pigs
with obesity-metabolic derangements. MATERIALS AND METHODS: We studied 14
domestic pigs after 16 weeks of a high fat/high fructose diet (obesity-metabolic
derangement group) or standard chow (lean group). Renal blood flow, glomerular
filtration rate and visceral fat volumes were studied in vivo by computerized
tomography. Renal arterial endothelial function was also studied ex vivo in organ
baths. RESULTS: Pigs with obesity-metabolic derangements demonstrated increased
body weight, blood pressure, cholesterol and intra-abdominal fat compared to lean
pigs and perirenal fat volume was significantly larger. Renal blood flow and
glomerular filtration rate were markedly elevated while urinary protein level was
preserved. Ex vivo acetylcholine induced, endothelium dependent vasodilation of
renal artery rings was substantially impaired in pigs with obesity-metabolic
derangements compared to lean pigs. Endothelial function was further blunted in
obesity-metabolic derangement and lean arterial rings by incubation with
perirenal fat harvested from pigs with obesity-metabolic derangements but not
from lean pigs. It was restored by inhibiting tumor necrosis factor-alpha.
Perirenal fat from pigs with obesity-metabolic derangements also showed increased
pro-inflammatory macrophage infiltration and tumor necrosis factor-alpha
expression. CONCLUSIONS: In pigs with obesity-metabolic derangements perirenal
fat directly causes renal artery endothelial dysfunction, which is partly
mediated by tumor necrosis factor-alpha.
PMID- 26417646
TI - An Increase in Gleason 6 Tumor Volume While on Active Surveillance Portends a
Greater Risk of Grade Reclassification with Further Followup.
AB - PURPOSE: We evaluated the relative risk of later grade reclassification and
outcomes of patients in whom high volume Gleason 6 prostate cancer develops while
on active surveillance. MATERIALS AND METHODS: A prospectively maintained
database was used to identify patients on active surveillance between 1998 and
2013. Tumor volume was assessed based on the number of positive cores and
proportion of core involvement. The chi-square and Fisher exact tests were used
for analysis as appropriate. The primary end point was the development of grade
reclassification, defined as grade only and/or grade and volume at the event
biopsy. RESULTS: A total of 555 men met the study inclusion criteria. Mean
followup was 46 months. Overall 70 patients demonstrated an increase in tumor
volume at or after biopsy 2. Compared to those men never experiencing volume or
grade reclassification, prostate specific antigen at diagnosis was not
significantly different (p=0.95), but median prostate volume was smaller in
patients who demonstrated volume reclassification (p <0.001). The incidence of
pure volume reclassification was 6.8%, 6.1% and 7.8% at biopsy 2, 3 and 4,
respectively. Men with volume reclassification were more likely to experience
later grade reclassification than those without at 33.3% vs 9.3%, respectively (p
<0.0001). CONCLUSIONS: While Gleason 6 prostate cancer has a favorable natural
history, it appears that patients on active surveillance who experience volume
reclassification are at substantially higher risk for grade reclassification.
Thus, urologists should pay close attention to tumor core involvement, and
monitoring should be adjusted accordingly for early volume reclassification in
younger men and those in good health.
PMID- 26417647
TI - Modulation of Lactobacillus casei bacteriophage A2 lytic/lysogenic cycles by
binding of Gp25 to the early lytic mRNA.
AB - The genetic switch of Lactobacillus casei bacteriophage A2 is regulated by the CI
protein, which represses the early lytic promoter PR and Cro that abolishes
expression from the lysogenic promoter PL . Lysogens contain equivalent cI and
cro-gp25 mRNA concentrations, i.e., CI only partially represses P(R), predicting
a lytic cycle dominance. However, A2 generates stable lysogens. This may be due
to Gp25 binding to the cro-gp25 mRNA between the ribosomal binding site and the
cro start codon, which abolishes its translation. Upon lytic cycle induction, CI
is partially degraded, cro-gp25 mRNA levels increase, and Cro accumulates,
launching viral progeny production. The concomitant concentration increase of
Gp25 restricts cro mRNA translation, which, together with the low but detectable
levels of CI late during the lytic cycle, promotes reentry of part of the cell
population into the lysogenic cycle, thus explaining the low proportion of L.
casei lysogens that become lysed (~ 1%). A2 shares its genetic switch structure
with many other Firmicutes phages. The data presented may constitute a model of
how these phages make the decision for lysis versus lysogeny.
PMID- 26417648
TI - Patient specific hemodynamic response functions associated with interictal
discharges recorded via simultaneous intracranial EEG-fMRI.
AB - Simultaneous collection of scalp EEG and fMRI has become an important tool for
studying the hemodynamic changes associated with interictal epileptiform
discharges (IEDs) in persons with epilepsy, and has become a standard presurgical
assessment tool in some centres. We previously demonstrated that performing EEG
fMRI using intracranial electrodes (iEEG-fMRI) is of low risk to patients in our
research centre, and offers unique insight into BOLD signal changes associated
with IEDs recorded from very discrete sources. However, it is unknown whether the
BOLD response corresponding to IEDs recorded by iEEG-fMRI follows the canonical
hemodynamic response. We therefore scanned 11 presurgical epilepsy patients using
iEEG-fMRI, and assessed the hemodynamic response associated with individual IEDs
using two methods: assessment of BOLD signal changes associated with isolated
IEDs at the location of the active intracranial electrode, and by estimating
subject-specific impulse response functions to isolated IEDs. We found that the
hemodynamic response associated with the intracranially recorded discharges
varied by patient and by spike location. The observed shape and timing
differences also deviated from the canonical hemodynamic response function
traditionally used in many fMRI experiments. It is recommended that future iEEG
fMRI studies of IEDs use a flexible hemodynamic response model when performing
parametric tests to accurately characterize these data.
PMID- 26417650
TI - Seminal plasma proteins and their relationship with percentage of morphologically
normal sperm in 2-year-old Brahman (Bos indicus) bulls.
AB - The objective was to determine the relationship between seminal plasma proteins
and sperm morphology in Bos indicus bulls of the Brahman breed. Fifty-six 24
month-old Australian Brahman bulls were electroejaculated and samples were
examined to determine the percentage of morphologically normal sperm (PNS24) and
the seminal plasma protein composition was identified and quantified by 2-D gel
electrophoresis. The total integrated optical density of 152 seminal plasma
protein spots (SPPs) across all gels was determined using the PDQuest software
version 8.0 (Bio Rad, USA). Using a single regression mixed model with the
density of individual spots as a covariate for PNS24, 17 SPPs were significantly
associated with PNS24 (p<0.05). A multiple regression analyses of these SPPs,
using three models; non-parametric Tree Model, Generalized Additive Model, and a
step-wise selection method were conducted, and 6 SPPs could be used to predict
PNS24; four SPPs had positive and two had negative association with PNS24.
Together these spots explained 35% of the phenotypic variation in PNS24. Using
mass spectrometry (MALDI-ToF and TripleToF-MS) the SPPs with positive
relationship contained mainly apolipoprotein A-I (1310), protein DJ-1 and
glutathione peroxidase 3 (2308), phosphoglycerate kinase 1 (6402) and
apolipoprotein A-I and secretoglobin family 1D member (8008). The SPPs inversely
associated with PNS24 were clusterin/seminal plasma protein A3 (1411) and
epididymal secretory protein E1 (8108). This is the first comprehensive report on
the association between seminal plasma protein composition in Bos indicus Brahman
bulls and sperm morphology.
PMID- 26417651
TI - TESS3: fast inference of spatial population structure and genome scans for
selection.
AB - Geography and landscape are important determinants of genetic variation in
natural populations, and several ancestry estimation methods have been proposed
to investigate population structure using genetic and geographic data
simultaneously. Those approaches are often based on computer-intensive stochastic
simulations and do not scale with the dimensions of the data sets generated by
high-throughput sequencing technologies. There is a growing demand for faster
algorithms able to analyse genomewide patterns of population genetic variation in
their geographic context. In this study, we present TESS3, a major update of the
spatial ancestry estimation program TESS. By combining matrix factorization and
spatial statistical methods, TESS3 provides estimates of ancestry coefficients
with accuracy comparable to TESS and with run-times much faster than the Bayesian
version. In addition, the TESS3 program can be used to perform genome scans for
selection, and separate adaptive from nonadaptive genetic variation using
ancestral allele frequency differentiation tests. The main features of TESS3 are
illustrated using simulated data and analysing genomic data from European lines
of the plant species Arabidopsis thaliana.
PMID- 26417649
TI - Effects of dietary n-6:n-3 fatty acid ratio and vitamin E on semen quality, fatty
acid composition and antioxidant status in boars.
AB - The aim of the present study was to evaluate the effects of dietary n-6:n-3 fatty
acid (FA) ratio and vitamin E on the semen quality, FA composition and
antioxidant status of boars. Forty-eight Landrace boars were randomly distributed
in a 3*2 factorial design with three n-6:n-3 FA ratios (14.4, 6.6 and 2.2) by the
inclusion of three oil sources (soybean, fish/soybean, fish) and two vitamin E
levels (200 and 400mg/kg). During the 8 weeks of treatment, semen parameters were
evaluated. Serum, sperm and seminal plasma samples were taken at 0 and 8 weeks to
monitor the FA composition and antioxidant status. Results showed that the 6.6
and 2.2 dietary ratios very effectively increased docosahexaenoic acid (DHA) and
n-3 polyunsaturated fatty acid (PUFA) and decreased docosapentaenoic acid (DPA)
and n-6:n-3 ratio in spermatozoa. The 6.6 dietary ratio contributed to a greater
progressive sperm motility (P<0.05) than the 14.4 and 2.2 dietary ratio, and this
ratio also enhanced the superoxide dismutase (SOD) and total antioxidant capacity
(TAC) (P<0.05) in seminal plasma more significantly than the other two ratios at
week 8. Compared with 200mg/kg supplementation of vitamin E, 400mg/kg
supplementation of vitamin E increased the progressive sperm motility, SOD of
sperm, TAC and SOD of seminal plasma and serum, and decreased sperm
malondialdehyde (MDA) (P<0.05). In conclusion, the 6.6 dietary ratio and 400mg/kg
vitamin E supplementation improve progressive sperm motility by modifying the
sperm FA composition and antioxidant status.
PMID- 26417652
TI - Close relationship between circumflex artery and left atrial appendage.
PMID- 26417653
TI - Changes in referral protocols for cardiac surgery: do financial considerations
come at a cost?
AB - INTRODUCTION AND OBJECTIVES: The aim of this study was to determine whether
changes to referral protocols for cardiac surgery have had an impact on waiting
times, hospitalizations and mortality during the waiting period and during the
first year of follow-up after surgery. METHODS: In this retrospective study of
patients referred for cardiac surgery between January 1, 2008 and September 30,
2014, the study population was divided into two groups: those referred before
(group A, January 1, 2008 to August 31, 2011) and after (group B, September 1,
2011 to September 30, 2014) the change in referral protocols. A telephone follow
up was conducted. RESULTS: There were 864 patients referred for cardiac surgery,
557 in group A and 307 in group B. Patient characteristics were similar between
groups. The mean waiting time for surgery was 10.6+/-18.5 days and 55.7+/-79.9
days in groups A and B, respectively (p=0.00). During the waiting period two
patients (0.4%) were hospitalized in group A and 28 (9.1%) in group B (p=0:00);
mortality was, respectively, 0% and 2.3% (p=0.00). During one-year follow-up
12.8% of group A patients and 16% of group B patients were hospitalized.
Cardiovascular mortality in this period was around 5% in both groups (p>0.05).
CONCLUSION: Changes to referral protocols for cardiac surgery had an impact on
waiting times, on the number of hospitalizations and on mortality in this period.
PMID- 26417654
TI - Infective endocarditis in an HIV-infected intravenous drug user.
AB - Infective endocarditis is a common complication among injecting drug users.
Disease risk among these patients is increased by the spread of HIV infection. In
the following article, we discuss the exceptional clinical presentation of a 28
year-old patient who used intravenous drugs (heroin) for 10 years, had been
infected with HIV for seven years and as a complication had developed
Staphylococcus aureus infective endocarditis. The patient came to the hospital in
serious condition, complaining of bodily pain, swelling of the legs and general
weakness. During hospitalization, besides infective endocarditis, she was also
diagnosed with anemia, toxic hepatitis, renal failure, ascites, sepsis, and
pneumonia. A completely disrupted tricuspid valve, damaged aortic valve, and
fibrosis of the mitral valve were detected. Echocardiographic and radiologic data
showed that the patient's condition continued to deteriorate day by day, with
significant progression of heart failure, ejection fraction decreasing from 45%
to 10%, and development of myocarditis, hydrothorax and pericarditis. However,
this progressive worsening of the patient's condition ceased when vancomycin was
administered. To the authors' knowledge, this is the first such case described in
the literature in which significant improvement was observed despite the
patient's complex condition with associated complications.
PMID- 26417655
TI - Looking into and beyond the heart.
PMID- 26417656
TI - Psoriasis strikes back! Epicardial adipose tissue: another contributor to the
higher cardiovascular risk in psoriasis.
AB - For many years psoriasis was considered an inflammatory condition restricted to
the skin. However, nowadays it is considered an immune-mediated, systemic
inflammatory condition associated with numerous medical comorbidities,
particularly cardiometabolic diseases, and overall cardiovascular mortality.
Several studies have suggested that psoriasis may be an independent risk factor
for atherosclerosis, indicating that psoriasis itself poses an intrinsic risk for
cardiovascular disease, probably due to the disease's inflammatory burden.
However, other causes beyond systemic inflammation and traditional cardiovascular
risk factors may be implicated in cardiovascular disease in psoriasis. Recently,
epicardial adipose tissue, an emerging cardiovascular risk factor, has been shown
to be increased in psoriasis patients and to be associated with subclinical
atherosclerosis, providing another possible link between psoriasis and
atherosclerosis. The reason for the increase in epicardial adipose tissue in
patients with psoriasis is unknown, but it is probably multifactorial, with
genetic, immune-mediated and behavioral factors having a role. Thus, along with
the increased prevalence of cardiometabolic risk factors and systemic
inflammation in psoriasis, epicardial adipose tissue is probably another
important contributor to the higher cardiovascular risk observed in psoriasis.
PMID- 26417657
TI - Preparing giant unilamellar vesicles (GUVs) of complex lipid mixtures on demand:
Mixing small unilamellar vesicles of compositionally heterogeneous mixtures.
AB - Giant unilamellar vesicles (GUVs) are simple model membrane systems of cell-size,
which are instrumental to study the function of more complex biological membranes
involving heterogeneities in lipid composition, shape, mechanical properties, and
chemical properties. We have devised a method that makes it possible to prepare a
uniform sample of ternary GUVs of a prescribed composition and heterogeneity by
mixing different populations of small unilamellar vesicles (SUVs). The validity
of the protocol has been demonstrated by applying it to ternary lipid mixture of
DOPC, DPPC, and cholesterol by mixing small unilamellar vesicles (SUVs) of two
different populations and with different lipid compositions. The compositional
homogeneity among GUVs resulting from SUV mixing is quantified by measuring the
area fraction of the liquid ordered-liquid disordered phases in giant vesicles
and is found to be comparable to that in GUVs of the prescribed composition
produced from hydration of dried lipids mixed in organic solvent. Our method
opens up the possibility to quickly increase and manipulate the complexity of GUV
membranes in a controlled manner at physiological buffer and temperature
conditions. The new protocol will permit quantitative biophysical studies of a
whole new class of well-defined model membrane systems of a complexity that
resembles biological membranes with rafts.
PMID- 26417658
TI - Prevalence and risk factors for colonization with methicillin resistant
Staphylococcus aureus and other Staphylococci species in hospitalized and farm
horses in Israel.
AB - Methicillin-resistant staphylococci (MRS), and specifically Methicillin-resistant
Staphylococcus aureus (MRSA) colonization or infection have become a serious
emerging condition in equine hospitals, with complex concerns regarding animals,
personnel and public health. The objectives of this study were to evaluate the
prevalence and risk factors for colonization by Staphylococci, MRS, and MRSA
among horses in Israel. Nasal swabs were collected from horses at 17 riding
stables (n=206), and from hospitalized horses admitted to a veterinary hospital
(n=84). Species identification was performed by pta gene PCR, RFLP analysis and
sequencing. MRS was identified by the presence of mecA. Genetic relatedness of
MRSA isolates was determined by spa typing and MLST. SCCmec-type and pvl gene
were determined. Univariable and multivariable statistical analysis were used to
identify potential risk factors. Colonization with Staphylococci was found among
3.8% of farm horses and 50.6% of hospitalized horses (p<0.05). MRS isolates were
not found in any of the farm horses, but were isolated from 21.6% of the horses
at the veterinary hospital, comprising 42.8% of all hospital isolates. MRSA was
found exclusively among hospitalized horses (7.2%). All MRSA isolates belonged to
a unique single multi-drug-resistant clone, ST5-SCCmec V, pvl-negative, spa-type
t535. Risk factors for colonization with MRS were pure bred, hospitalization and
antibiotic use. This is the first surveillance study of Staphylococci in horses
in Israel, and the first report on the presence of a unique MRSA strain among
hospital horses, recognizing the veterinary hospital as a potential reservoir for
MRSA, an antibiotic resistant pathogen with human relevance.
PMID- 26417659
TI - Plasma IL-1Ra: linking hyperapoB to risk factors for type 2 diabetes independent
of obesity in humans.
AB - BACKGROUND/OBJECTIVE: Plasma apoB predicts the incidence of type 2 diabetes
(T2D); however, the link between apoB-linpoproteins and risks for T2D remain
unclear. Insulin resistance (IR) and compensatory hyperinsulinemia characterize
prediabetes, and the involvement of an activated interleukin-1 (IL-1) family,
mainly IL-1beta and its receptor antagonist (IL-Ra), is well documented. ApoB
lipoproteins were reported to promote IL-1beta secretion in immune cells;
however, in vivo evidence is lacking. We hypothesized that obese subjects with
hyperapoB have an activated IL-1 system that explains hyperinsulinemia and IR in
these subjects. SUBJECTS/METHODS: We examined 81 well-characterized normoglycemic
men and postmenopausal women (?27 kg m(-2), 45-74 years, non-smokers, sedentary,
free of chronic disease). Insulin secretion and sensitivity were measured by the
gold-standard Botnia clamp, which is a combination of a 1-h intravenous glucose
tolerance test (IVGTT) followed by 3-h hyperinsulinemic euglycemic clamp.
RESULTS: Plasma IL-1beta was near detection limit (0.071-0.216 pg ml(-1)), while
IL-1Ra accumulated at 1000-folds higher (77-1068 pg ml(-1)). Plasma apoB (0.34
1.80 g l(-1)) associated significantly with hypersinsulinemia (totalIVGTT: C
peptide r=0.27, insulin r=0.22), IR (M/I=-0.29) and plasma IL-1Ra (r=0.26) but
not with IL-1beta. Plasma IL-1Ra associated with plasma IL-1beta (r=0.40), and
more strongly with hyperinsulinemia and IR than apoB, while the association of
plasma IL-1beta was limited to second phase and total insulin secretion (r=0.23).
Adjusting the association of plasma apoB to hyperinsulinemia and IR for IL-1Ra
eliminated these associations. Furthermore, despite equivalent body composition,
subjects with hyperapoB (?80th percentile, 1.14 g l(-1)) had higher C-peptide
secretion and lower insulin sensitivity than those with low plasma apoB (?20th
percentile, 0.78 g l(-1)). Adjustment for plasma IL-1 Ra eliminated all group
differences. CONCLUSION: Plasma apoB is associated with hyperinsulinemia and IR
in normoglycemic obese subjects, which is eliminated upon adjustment for plasma
IL-1Ra. This may implicate the IL-1 family in elevated risks for T2D in obese
subjects with hyperapoB.
PMID- 26417661
TI - The shadow of the future promotes cooperation in a repeated prisoner's dilemma
for children.
AB - Cooperation among genetically unrelated individuals can be supported by direct
reciprocity. Theoretical models and experiments with adults show that the
possibility of future interactions with the same partner can promote cooperation
via conditionally cooperative strategies such as tit-for-tat (TFT). Here, we
introduce a novel implementation of the repeated Prisoner's Dilemma (PD) designed
for children to examine whether repeated interactions can successfully promote
cooperation in 10 and 11 year olds. We find that children cooperate substantially
more in repeated PDs than in one-shot PDs. We also find that girls cooperate more
than boys, and that children with more conduct problems cooperate less. Finally,
we find that children use conditional cooperation strategies but that these
strategies vary by gender and conduct problem rating. Specifically, girls and
children with few conduct problems appear to follow an altruistic version of win
stay, lose-shift (WSLS), attempting to re-establish cooperation after they had
defected. Boys and children with more conduct problems appear to follow a Grim
strategy, defecting for the duration after the partner defects. Thus we provide
evidence that children utilize the power of direct reciprocity to promote
cooperation in strategic interactions and that, by late elementary school,
distinct strategies of conditional cooperation have emerged.
PMID- 26417660
TI - Importance of the type of provider seen to begin health care for a new episode
low back pain: associations with future utilization and costs.
AB - RATIONALE, AIMS AND OBJECTIVE: Low back pain (LBP) care can involve many
providers. The provider chosen for entry into care may predict future health care
utilization and costs. The objective of this study was to explore associations
between entry settings and future LBP-related utilization and costs. METHODS: A
retrospective review of claims data identified new entries into health care for
LBP. We examined the year after entry to identify utilization outcomes (imaging,
surgeon or emergency visits, injections, surgery) and total LBP-related costs.
Multivariate models with inverse probability weighting on propensity scores were
used to evaluate relationships between utilization and cost outcomes with entry
setting. RESULTS: 747 patients were identified (mean age = 38.2 (+/- 10.7) years,
61.2% female). Entry setting was primary care (n = 409, 54.8%), chiropractic (n =
207, 27.7%), physiatry (n = 83, 11.1%) and physical therapy (n = 48, 6.4%).
Relative to primary care, entry in physiatry increased risk for radiographs (OR =
3.46, P = 0.001), advanced imaging (OR = 3.38, P < 0.001), injections (OR = 4.91,
P < 0.001), surgery (OR = 4.76, P = 0.012) and LBP-related costs (standardized
Beta = 0.67, P < 0.001). Entry in chiropractic was associated with decreased risk
for advanced imaging (OR = 0.21, P = 0.001) or a surgeon visit (OR = 0.13, P =
0.005) and increased episode of care duration (standardized Beta = 0.51, P <
0.001). Entry in physical therapy decreased risk of radiographs (OR = 0.39, P =
0.017) and no patient entering in physical therapy had surgery. CONCLUSIONS:
Entry setting for LBP was associated with future health care utilization and
costs. Consideration of where patients chose to enter care may be a strategy to
improve outcomes and reduce costs.
PMID- 26417663
TI - Biofilm Formation of Staphylococcus aureus on Various Surfaces and Their
Resistance to Chlorine Sanitizer.
AB - This study investigated the effect of material types (polystyrene, polypropylene,
glass, and stainless steel) and glucose addition on Staphylococcus aureus biofilm
formation, and the relationship between biofilm formation measured by crystal
violet (CV) staining and the number of biofilm cells determined by cell counts
was studied. We also evaluated the efficacy of chlorine sanitizer on inhibiting
various different types of S. aureus biofilms on the surface of stainless steel.
Levels of biofilm formation of S. aureus were higher on hydrophilic surfaces
(glass and stainless steel) than on hydrophobic surfaces (polypropylene and
polystyrene). With the exception of biofilm formed on glass, the addition of
glucose in broth significantly increased the biofilm formation of S. aureus on
all surfaces and for all tested strains (P <= 0.05). The number of biofilm cells
was not correlated with the biomass of the biofilms determined using the CV
staining method. The efficacy of chlorine sanitizer against biofilm of S. aureus
was not significantly different depending on types of biofilm (P > 0.05).
Therefore, further studies are needed in order to determine an accurate method
quantifying levels of bacterial biofilm and to evaluate the resistance of
bacterial biofilm on the material surface. PRACTICAL APPLICATION: Biofilm
formation of Staphylococcus aureus on the surface was different depending on the
surface characteristics and S. aureus strains. There was low correlation between
crystal violet staining method and viable counts technique for measuring levels
of biofilm formation of S. aureus on the surfaces. These results could provide
helpful information for finding and understanding the quantification method and
resistance of bacterial biofilm on the surface.
PMID- 26417662
TI - Integration of a transfected gene into the genome of Babesia bovis occurs by
legitimate homologous recombination mechanisms.
AB - This study examines the patterns of gene integration of gfp-bsd upon stable
transfection into the T3Bo strain of Babesia bovis using a plasmid designed to
integrate homologous sequences of the parasite's two identical ef-1alpha A and B
genes. While the transfected BboTf-149-6 cell line displayed two distinct
patterns of gene integration, clonal lines derived from this strain by cell
sorting contained only single gfp-bsd insertions. Whole genome sequencing of two
selected clonal lines, E9 and C6, indicated two distinct patterns of gfp-bsd
insertion occurring by legitimate homologous recombination mechanisms: one into
the expected ef-1alpha orf B, and another into the ef-1alpha B promoter. The data
suggest that expression of the ef-1alpha orf B is not required for development of
B. bovis in cultured erythrocyte stages. Use of legitimate homologous
recombination mechanisms in transfected B. bovis supports the future use of
transfection methods for developing efficient gene function assignment
experiments using gene knockout techniques.
PMID- 26417664
TI - Polymorphism of PXR gene associated with the increased risk of drug-induced liver
injury in Indonesian pulmonary tuberculosis patients.
AB - WHAT IS KNOWN AND OBJECTIVE: Tuberculosis is still a major infectious disease in
Indonesia. Patients are treated mostly using fixed-dose combination treatment in
primary public health facilities. The incidence of antituberculosis drug-induced
liver injury (AT-DILI) is approximately 10% among Indonesian tuberculosis
patients who used standard fixed combination regimens during the intensive phase
of treatment. However, information regarding genetic polymorphism associated with
the increase risk of drug-induced liver injury is still limited. The aim of this
study was to investigate pregnane X receptor (PXR) gene polymorphisms as one of
the risk factors of AT-DILI. METHODS: In this prospective cohort study, we
recruited 106 adult patients diagnosed with pulmonary tuberculosis and treated
with category I FDC (fixed-dose combination). The identification of SNP -25385C>T
(rs3814055) was conducted by ARMS (amplification refractory mutation system).
Hepatotoxicity was defined as ALT and/or AST levels above the normal threshold on
the second, fourth and sixth months of monitoring during tuberculosis treatment.
RESULTS AND DISCUSSION: The logistic regression analysis showed that patients
with the TT genotype of PXR gene (rs3814055) significantly had a greater risk of
AT-DILI (OR 8.89; 95% CI 1.36-57.93, P < 0.05), compared with those of wild-type
CC genotype. WHAT IS NEW AND CONCLUSION: The result suggests that in Indonesian
patients with tuberculosis, the risk of having AT-DILI was associated with TT
genotype of the PXR gene.
PMID- 26417665
TI - Mechanism of Polyphosphates Hydrolysis by Purified Polyphosphatases from the
Dorsal Muscle of Silver Carp (Hypophthalmichthys Molitrix) as Detected by 31P
NMR.
AB - The dynamic hydrolysis of tetrasodium pyrophosphate (TSPP), sodium
tripolyphosphate (STPP) and polyphosphate compound, which was catalyzed by
purified pyrophosphatase (PPase) and myosin- tripolyphosphatase (TPPase) from the
silver carp dorsal muscle, was studied using (31) P NMR spectroscopy. In the
PPase + TSPP system, the pyrophosphate (PP) was hydrolyzed quickly and completely
within 8 h and the hydrolysis rate of PP was 12.51%/h. In the TPPase + STPP
system, the first-order hydrolysis of tripolyphosphate (TPP) was not yet complete
after 48 h, and the derived PP accumulated progressively. Given the coexistence
of PPase and TPPase, only 1.20% of TPP in STPP alone remained after 48 h.
However, the generation rate of Pi in the polyphosphate compound (TSPP: STPP:
sodium hexametaphosphate = 1: 8: 1) was 0.76%/h, which was less than 0.88%/h in
STPP alone. In the presence of polyphosphatases, the decrease of PP or TPP
content in the polyphosphate compound was not as rapid as that in TSPP or STPP
alone due to the inhibitory effect of PP on TPPase and the effect of low system
pH on PPase. The understanding of polyphosphates hydrolysis mechanism was capable
of developing the advanced polyphosphate mixture in order to reduce the phosphate
residue in fish products. PRACTICAL APPLICATION: Processors appreciate the proven
value of phosphates to increase the yield and functionality of the fish meat
products. Our studies showed that the hydrolysis rate of PP or TPP in the blend
was slower than that of polyphosphate alone. Thus, it is likely that the addition
of PP and TPP in a polyphosphate blend had a prolonged interaction with proteins
in fish meat processing and the effectiveness of polyphosphates was enhanced.
PMID- 26417666
TI - PATIENTS EXPERIENCES OF INVOLVEMENT IN CHOICE OF DIALYSIS MODE.
AB - BACKGROUND: International guidelines recommend that patients choose dialysis mode
based on their own values and preferences; thus, involvement is needed in
dialysis choice. A literature review indicated a lack of knowledge concerning
patient involvement in decision-making, especially concerning patients'
experiences of the decision-making process just after making the decision and
before starting dialysis. OBJECTIVES: To gather information about how patients
experienced involvement in the decision-making process of renal substation
therapy just after they have made the decision and before starting dialysis.
METHODS: A qualitative method with a phenomenological and hermeneutic approach.
The study was based on individual semi-structured interviews with nine adult
patients with chronic kidney disease. A data-driven analysis based on systematic
text condensation was used. FINDINGS: Patients are a significant part of the
decision. Health care professionals contribute to the experience of being
involved. Patients keep putting off the final choice. CONCLUSION: The patients
found themselves involved in the choice of dialysis mode and have different views
on what is needed to feel being involved. Information, interaction, and advice
from health care professionals affect this experience. However, the experience of
not having any symptoms caused patients to put off the final choice of dialysis
mode.
PMID- 26417667
TI - Sodium MRI radiofrequency coils for body imaging.
AB - The proliferation of high-field whole-body systems, advances in gradient
performance and refinement of signal-to-noise ratio (SNR)-efficient short-TE
sequences suitable for sodium imaging have led to a resurgence of interest in
sodium imaging for body applications. With this renewed interest has come
increased demand for SNR-efficient sodium coils. Efficient coils can
significantly increase SNR in sodium imaging, allowing higher resolutions and/or
shorter scan times. In this work, we focus on body imaging applications of sodium
MRI, and review developments in MRI radiofrequency (RF) coil topologies for
sodium imaging. We first provide a brief discussion of RF coil design
considerations in sodium imaging. This is followed by an overview of common coil
topologies, their advantages and disadvantages, and examples of each.
PMID- 26417668
TI - Increased visual cortical thickness in sight-recovery individuals.
AB - Individuals who are born blind due to dense bilateral cataracts and who later
regain vision due to cataract surgery provide a unique model to evaluate the
effect of early sensory experience in humans. In recent years, several studies
have started to assess the functional consequences of early visual deprivation in
these individuals, revealing a number of behavioral impairments in visual and
multisensory functions. In contrast, the extent to which a transient period of
congenital visual deprivation impacts brain structure has not yet been
investigated. The present study investigated this by assessing cortical thickness
of occipital areas in a group of six cataract-reversal individuals and a group of
six age-matched normally sighted controls. This analysis revealed higher cortical
thickness in cataract-reversal individuals in the left calcarine sulcus, in the
superior occipital gyrus and in the transverse occipital sulcus bilaterally. In
addition, occipital cortical thickness correlated negatively with behavioral
performance in an audio-visual task for which visual input was critical, and
positively with behavioral performance in auditory tasks. Together, these results
underscore the critical role of early sensory experience in shaping brain
structure and suggest that increased occipital cortical thickness, while
potentially compensatory for auditory sensory processing, might be maladaptive
for visual recovery in cases of sight restoration.
PMID- 26417669
TI - Feasibility and reproducibility of BOLD and TOLD measurements in the liver with
oxygen and carbogen gas challenge in healthy volunteers and patients with
hepatocellular carcinoma.
AB - PURPOSE: To quantify baseline relaxation rates R2* and R1 in the abdomen, their
changes after respiratory challenges, and their reproducibility in healthy
volunteers and patients with hepatocellular carcinoma (HCC) at 1.5T and 3.0T.
MATERIALS AND METHODS: R2* measurements were acquired in the liver in 8
volunteers and 27 patients with 34 HCCs using multiecho T2* at baseline and after
respiratory challenges with 100% oxygen (O2 ) and carbogen (CB = 95%O2 /5%CO2 ).
R1 was measured at 1.5T in one volunteer and 21 patients with 23 HCCs. Test
retest coefficient of variation (CV) was assessed in 10 subjects. Intra- and
interobserver variability of R2* and R1 measurements was assessed in 12 and 10
patients, respectively. Parameters for HCC, liver, and muscle were compared
between baseline and after gas challenges. RESULTS: We observed that R2* and R1
imaging of HCCs with O2 and CB is feasible and reproducible (test-retest CV
R2*<15%/R1 <5%; intra- and interobserver intraclass correlation coefficient
R2*>0.88/R1 >0.7 and CV R2*<7%/R1 <3% at 1.5T). R2* measurements were observed to
be less reproducible at 3.0T (CV<35%). There was a statistically significant
decrease in R2* values in HCC before and after O2 (P = 0.02) and increase in R1
after O2 (P = 0.004). CB had no significant effect (P R2* = 0.47/R1 = 0.278).
CONCLUSION: R2* measurements in HCC and liver parenchyma are more reproducible at
1.5T than at 3.0T, and with O2 than with CB challenge. We observed a decrease in
R2* and an increase in R1 of HCCs from baseline in response to O2 challenge, as
expected with increased tissue and blood oxygenation.
PMID- 26417670
TI - Oxidative stress promotes benign prostatic hyperplasia.
AB - BACKGROUND: Benign prostatic hyperplasia (BPH) is characterized by increased
tissue mass in the transition zone of the prostate, which leads to obstruction of
urine outflow and significant morbidity in the majority of older men. Plasma
markers of oxidative stress are increased in men with BPH but it is unclear
whether oxidative stress and/or oxidative DNA damage are causal in the
pathogenesis of BPH. METHODS: Levels of 8-OH deoxyguanosine (8-OH dG), a marker
of oxidative stress, were measured in prostate tissues from normal transition
zone and BPH by ELISA. 8-OH dG was also detected in tissues by
immunohistochemistry and staining quantitated by image analysis. Nox4 promotes
the formation of reactive oxygen species. We therefore created and characterized
transgenic mice with prostate specific expression of Nox4 under the control of
the prostate specific ARR2PB promoter. RESULTS: Human BPH tissues contained
significantly higher levels of 8-OH dG than control transition zone tissues and
the levels of 8-OH dG were correlated with prostate weight. Cells with 8-OH dG
staining were predominantly in the epithelium and were present in a patchy
distribution. The total fraction of epithelial staining with 8-OH dG was
significantly increased in BPH tissues by image analysis. The ARR2PB-Nox4 mice
had increased oxidative DNA damage in the prostate, increased prostate weight,
increased epithelial proliferation, and histological changes including epithelial
proliferation, stromal thickening, and fibrosis when compared to wild type
controls. CONCLUSIONS: Oxidative stress and oxidative DNA damage are important in
the pathogenesis of BPH.
PMID- 26417671
TI - A 3D map of the islet routes throughout the healthy human pancreas.
AB - Islets of Langerhans are fundamental in understanding diabetes. A healthy human
pancreas from a donor has been used to asses various islet parameters and their
three-dimensional distribution. Here we show that islets are spread gradually
from the head up to the tail section of the pancreas in the form of contracted or
dilated islet routes. We also report a particular anatomical structure, namely
the cluster of islets. Our observations revealed a total of 11 islet clusters
which comprise of small islets that surround large blood vessels. Additional
observations in the peripancreatic adipose tissue have shown lymphoid-like nodes
and blood vessels captured in a local inflammatory process. Our observations are
based on regional slice maps of the pancreas, comprising of 5,423 islets. We also
devised an index of sphericity which briefly indicates various islet shapes that
are dominant throughout the pancreas.
PMID- 26417672
TI - Reasoning About Cultural and Genetic Transmission: Developmental and Cross
Cultural Evidence From Peru, Fiji, and the United States on How People Make
Inferences About Trait Transmission.
AB - Using samples from three diverse populations, we test evolutionary hypotheses
regarding how people reason about the inheritance of various traits. First, we
provide a framework for differentiat-ing the outputs of mechanisms that evolved
for reasoning about variation within and between (a) biological taxa and (b)
culturally evolved ethnic categories from (c) a broader set of beliefs and
categories that are the outputs of structured learning mechanisms. Second, we
describe the results of a modified "switched-at-birth" vignette study that we
administered among children and adults in Puno (Peru), Yasawa (Fiji), and adults
in the United States. This protocol permits us to study perceptions of prenatal
and social transmission pathways for various traits and to differentiate the
latter into vertical (i.e., parental) versus horizontal (i.e., peer) cultural
influence. These lines of evidence suggest that people use all three mechanisms
to reason about the distribution of traits in the population. Participants at all
three sites develop expectations that morphological traits are under prenatal
influence, and that belief traits are more culturally influenced. On the other
hand, each population holds culturally specific beliefs about the degree of
social influence on non-morphological traits and about the degree of vertical
transmission-with only participants in the United States expecting parents to
have much social influence over their children. We reinterpret people's
differentiation of trait transmission pathways in light of humans' evolutionary
history as a cultural species.
PMID- 26417673
TI - Neural basis of disgust perception in racial prejudice.
AB - Worldwide racial prejudice is originated from in-group/out-group discrimination.
This prejudice can bias face perception at the very beginning of social
interaction. However, little is known about the neurocognitive mechanism
underlying the influence of racial prejudice on facial emotion perception. Here,
we examined the neural basis of disgust perception in racial prejudice using a
passive viewing task and functional magnetic resonance imaging. We found that
compared with the disgusted faces of in-groups, the disgusted faces of out-groups
result in increased amygdala and insular engagement, positive coupling of the
insula with amygdala-based emotional system, and negative coupling of the insula
with anterior cingulate cortex (ACC)-based regulatory system. Furthermore,
machine-learning algorithms revealed that the level of implicit racial prejudice
could be predicted by functional couplings of the insula with both the amygdala
and the ACC, which suggests that the insula is largely involved in racially
biased disgust perception through two distinct neural circuits. In addition,
individual difference in disgust sensitivity was found to be predictive of
implicit racial prejudice. Taken together, our results suggest a crucial role of
insula-centered circuits for disgust perception in racial prejudice.
PMID- 26417674
TI - Dissociation of perception and action in audiovisual multisensory integration.
AB - The 'temporal rule' of multisensory integration (MI) proposes that unisensory
stimuli, and the neuronal responses they evoke, must fall within a window of
integration. Ecological validity demands that MI should occur only for physically
simultaneous events (which may give rise to non-simultaneous neural activations),
and spurious neural response simultaneities unrelated to environmental
multisensory occurrences must somehow be rejected. Two experiments investigated
the requirements of simultaneity for facilitative MI. Experiment 1 employed an
reaction time (RT)/race model paradigm to measure audiovisual (AV) MI as a
function of AV stimulus-onset asynchrony (SOA) under fully dark adapted
conditions for visual stimuli that were either rod- or cone-isolating. Auditory
stimulus intensity was constant. Despite a 155-ms delay in mean RT to the
scotopic vs. photopic stimulus, facilitative AV MI in both conditions occurred
exclusively at an AV SOA of 0 ms. Thus, facilitative MI demands both physical and
physiological simultaneity. Experiment 2 investigated the accuracy of
simultaneity and temporal order judgements under the same stimulus conditions.
Judgements of AV stimulus simultaneity or temporal order were significantly
influenced by stimulus intensity, indicating different simultaneity requirements
for these tasks. The possibility was considered that there are mechanisms by
which the nervous system may take account of variations in response latency
arising from changes in stimulus intensity in order to selectively integrate only
those physiological simultaneities that arise from physical simultaneities. It
was proposed that separate subsystems for AV MI exist that pertain to action and
perception.
PMID- 26417676
TI - THE ASSOCIATION BETWEEN MENSTRUAL CYCLE CHARACTERISTICS AND PERCEIVED BODY IMAGE:
A CROSS-SECTIONAL SURVEY OF POLISH FEMALE ADOLESCENTS.
AB - The increasing prevalence of negative body perceptions among adolescent girls and
the tendency towards wishing to be thinner have become a cultural norm in Western
culture. Adolescent girls are particularly vulnerable to developing a negative
body image due to physical and sexual changes occurring during puberty. This
study aimed to evaluate the association between different measures of body image
perceptions and different phases of the menstrual cycle after controlling for
weight status and other potential confounders in Polish adolescent girls aged 12
18 years. Three-hundred and thirty participants of a cross-sectional survey
conducted in 2009, normally cycling and with no eating disorders, completed a
background questionnaire and the Stunkard Figure Rating Scale, and their
anthropometric measurements were collected. The dependent outcome variables were
measures of body image (actual body image, ideal body image and ideal-self
discrepancy) and dichotomous body image perception (satisfied versus
dissatisfied) adjusted for other predictor factors: socio-demographic variables,
menstrual history and cycle phases, and weight status. One-way ANOVA indicated
that weight status, age at menarche and menstrual cycle phase were associated
with actual body image and rate of ideal-self discrepancy. Ideal body image was
associated with weight status and menstrual cycle phase. General logistic
regression models were constructed to evaluate associations of body
dissatisfaction and all potential predictor variables. The final selected model
of the multiple logistic regression analysis using the backward elimination
procedure revealed that adjusted for other factors, negative body image was
significantly associated with different phases of the menstrual cycle (p
trend=0.033) and increasing body weight status (p trend=0.0007). The likelihood
of body dissatisfaction was greatest during the premenstrual phase of the
menstrual cycle (OR=2.38; 95% CI 1.06, 5.32) and among girls in obesity class I
(OR=8.04; 95% CI 2.37, 27.26). The study confirmed the association between body
image dissatisfaction in adolescent girls and different phases of the menstrual
cycle after controlling for weight status. The issue of negative body self-image
is not only of cognitive, but also of practical value as understanding better the
factors contributing to the formation of a negative body image may be
instrumental in developing preventive health programmes targeted at young people.
PMID- 26417675
TI - Lectin-induced agglutination method of urinary exosomes isolation followed by mi
RNA analysis: Application for prostate cancer diagnostic.
AB - BACKGROUND: Prostate cancer is the most common cancer in men. Prostate-specific
antigen has, however, insufficient diagnostic specificity. Novel complementary
diagnostic approaches are greatly needed. MiRNAs are small regulatory RNAs which
play an important role in tumorogenesis and are being investigated as a cancer
biomarker. In addition to their intracellular regulatory functions, miRNAs are
secreted into the extracellular space and can be found in various body fluids,
including urine. The stability of extracellular miRNAs is defined by association
with proteins, lipoprotein particles, and membrane vesicles. Among the known
forms of miRNA packaging, tumour-derived exosome-enclosed miRNAs is thought to
reflect the vital activity of cancer cells. The assessment of the exosomal
fraction of urinary miRNA may present a new and highly specific method for
prostate cancer diagnostics; however, this is challenged by the absence of
reliable and inexpensive methods for isolation of exosomes. METHODS: Prostate
cancer (PC) cell lines and urine samples collected from 35 PC patients and 35
healthy donors were used in the study. Lectins, phytohemagglutinin, and
concanavalin A were used to induce agglutination of exosomes. The efficiency of
isolation process was evaluated by AFM and DLS assays. The protein content of
isolated exosomes was analysed by western blotting. Exosomal RNA was assayed by
automated electrophoresis and expression level of selected miRNAs was evaluated
by RT-qPCR. The diagnostic potency of the urinary exosomal miRNA assessment was
estimated by the ROC method. RESULTS: The formation of multi-vesicular
agglutinates in urine can be induced by incubation with lectin at a final
concentration of 2 mg/ml. These agglutinates contain urinary exosomes and may be
pelleted by centrifugation with a relatively low G-force. The analysis of PC
related miRNA in urinary exosomes revealed significant up-regulation of miR-574
3p, miR-141-5p, and miR-21-5p associated with PC. CONCLUSIONS: Lectin-induced
aggregation is a low-cost and easily performed method for isolation of exosomes
from urine. Isolated exosomes can be further analysed in terms of miRNA content.
The miRNA profile of urinary exosomes reflects development of prostate cancer and
may present a promising diagnostic tool.
PMID- 26417677
TI - Baroreceptor activation therapy: The importance of targeting the right patient:
who needs to be treated?
PMID- 26417678
TI - Dependence on epiphytic bacteria for freezing protection in an Antarctic moss,
Bryum argenteum.
AB - Mosses are the dominant flora of Antarctica, but their mechanisms of survival in
the face of extreme low temperatures are poorly understood. A variety of Bryum
argenteum from 77 degrees S was previously shown to have strong ice-pitting
activity, a sign of the presence of ice-binding proteins (IBPs) that mitigate
freezing damage. Here, using samples that had been stored at -25(o) C for 10
years, it is shown that much if not all of the activity is due to bacterial ice
binding proteins secreted on the leaves of the moss. Sequencing of the leaf
metagenome revealed the presence of hundreds of genes from a variety of bacteria
(mostly Actinobacteria and Bacteroidetes) that encode a domain (DUF3494) that is
associated with ice binding. The frequency of occurrence of this domain is one to
two orders of magnitude higher than it is in representative mesophilic bacterial
metagenomes. Genes encoding 42 bacterial IBPs with N-terminal secretion signals
were assembled. There appears to be a commensal relationship in which the moss
provides sustenance to the bacteria in return for freezing protection.
PMID- 26417679
TI - The anterior paraventricular thalamus modulates neuronal excitability in the
suprachiasmatic nuclei of the rat.
AB - The suprachiasmatic nucleus (SCN) in mammals is the master clock which regulates
circadian rhythms. Neural activity of SCN neurons is synchronized to external
light through the retinohypothalamic tract (RHT). The paraventricular thalamic
nucleus (PVT) is a neural structure that receives synaptic inputs from, and
projects back to, the SCN. Lesioning the anterior PVT (aPVT) modifies the
behavioral phase response curve induced by short pulses of bright light. In order
to study the influence of the aPVT on SCN neural activity, we addressed whether
the stimulation of the aPVT can modulate the electrical response of the SCN to
either retinal or RHT stimulation. Using in vitro and in vivo recordings, we
found a large population of SCN neurons responsive to the stimulation of either
aPVT or RHT pathways. Furthermore, we found that simultaneous stimulation of the
aPVT and the RHT increased neuronal responsiveness and spontaneous firing rate
(SFR) in neurons with a low basal SFR (which also have more negative membrane
potentials), such as quiescent and arrhythmic neurons, but no change was observed
in neurons with rhythmic firing patterns and more depolarized membrane
potentials. These results suggest that inputs from the aPVT could shift the
membrane potential of an SCN neuron to values closer to its firing threshold and
thus contribute to integration of the response of the circadian clock to light.
PMID- 26417680
TI - Natural resources and the spread of HIV/AIDS: Curse or blessing?
AB - This paper answers two questions: "What impact have natural resources had on the
spread of the HIV epidemic so far?" and "What role can natural resource rents
play in order to finance the long-run response to HIV/AIDS?" Using a panel
dataset covering 137 countries from 1990 until 2008, de Soysa and Gizelis (2013)
provided evidence in Social Science & Medicine that oil-rich countries are more
deeply affected by the HIV and TB epidemics. They concluded that government of
resource-rich countries failed to implement effective public policies for dealing
with the epidemics. In this paper, I show that their results are (1) not robust,
(2) based on an inappropriate choice of dependent variable and (3) spurious
because series are non-stationary. After correcting for these issues, I find no
robust relationship between resource rents and the spread of HIV and TB. The
paper concludes by emphasizing the potential of natural resources rents for
financing the long-term liability brought about by the HIV/AIDS epidemic in sub
Saharan Africa.
PMID- 26417682
TI - DPF2 regulates OCT4 protein level and nuclear distribution.
AB - The amount of transcription factor OCT4 is strictly regulated. A tight regulation
of OCT4 levels is crucial for mammalian embryonic development and oncogenesis.
However, the mechanisms underlying regulation of OCT4 protein expression and
nuclear distribution are largely unknown. Here, we report that DPF2, a plant
homeodomain (PHD) finger protein, is upregulated during H9 cell differentiation
induced by retinoic acid. Endogenous interaction between DPF2 and OCT4 in P19
cells was revealed by an immunoprecipitation assay. GST-pull down assay proved
that OCT4 protein in H9 cells and recombinant OCT4 can precipitate with DPF2 in
vitro. In vitro ubiquitination assay demonstrated DPF2 might serve as an E3
ligase. Knock down of dpf2 using siRNA increased OCT4 protein level and stability
in P19 cells. DPF2 siRNAs also up-regulates OCT4 but not NANOG in H9 cells.
However, RA fails to downregulates OCT4 protein level in cells infected by
lenitviruses containing DPF2 siRNA. Moreover, overexpression of both DPF2 and
OCT4 in 293 cells proved the DPF2-OCT4 interaction. DPF2 but not PHD2 mutant DPF2
enhanced ubiquitination and degradation of OCT4 in 293 cells co-expressed DPF2
and OCT4. Both wild type DPF2 and PHD2 mutant DPF2 redistributes nuclear OCT4
without affecting DPF2-OCT4 interaction. Further analysis indicated that DPF2
decreases monomeric and mono-ubiquitinated OCT4, assembles poly-ubiquitin chains
on OCT4 mainly through Ub-K48 linkage. These findings contribute to an
understanding of how OCT4 protein level and nuclear distribution is regulated by
its associated protein.
PMID- 26417681
TI - Loss of calbindin-D28K is associated with the full range of tangle pathology
within basal forebrain cholinergic neurons in Alzheimer's disease.
AB - Basal forebrain cholinergic neurons (BFCN) are selectively vulnerable in
Alzheimer's disease (AD). We have shown that most of the BFCN in the human brain
contain the calcium-binding protein calbindin-D28K (CB), a large proportion lose
their CB in the course of normal aging, and the BFCN which degenerate in AD lack
CB. Here, we investigated the relationship between CB in the BFCN and the process
of tangle formation in AD using antibodies to tau epitopes that appear early,
intermediate or late in the process of tangle formation. Very small percentages
(0%-3.7%) of CB-positive BFCN contained pretangles and/or tangles, and very small
percentages (0%-5%) of the total BFCN pretangles and/or tangles were in CB
immunoreactive neurons. The number of CB-positive BFCN which contained tau
immunoreactivity was highest for the early epitope and lower for intermediate
epitopes. A late appearing epitope was absent from CB-positive BFCN. Age-related
loss of CB appears to coincide with tangle formation in the BFCN and is
associated with the full range of tau pathology, including late appearing
epitopes.
PMID- 26417684
TI - Cecal inoculum peritonitis: An alternative model for sepsis vascular dysfunction
study.
AB - AIMS: Sepsis is a life threatening condition that is characterized by the loss of
vascular reactivity. The factor(s) responsible for the diminished vascular
function seen in sepsis are not well understood. The purpose of this study was to
characterize the vascular dysfunction from the rat cecal inoculum (CI) sepsis
model using cecal ligation and puncture (CLP), and lipopolysaccharide (LPS)
sepsis as reference models. MATERIALS AND METHODS: Experiments were performed on
isolated aorta from CI, CLP and LPS treated rats using a combination of
pharmacological approaches. KEY FINDINGS: Phenylephrine (PE)-induced aortic
contraction was significantly decreased in each model (p<0.05) and not normalized
by L-NAME or indomethacin. The vascular response elicited in the CI model for
acetylcholine (Ach) was more similar to that seen in the CLP than the LPS model.
The removal of the endothelial layer increased sensitivity to L-NAME (p<0.05) in
aortae from CI group. Inhibition of the large conductance Ca(2+)/voltage
sensitive K(+) (BKCa) channel did not normalize PE hyporesponsiveness but did
abolish sepsis-induced contractile oscillation. Inhibition of the voltage
dependent Kv1.5 channel was not able to reverse the vascular hyporesponsiveness,
however, inhibition of the ATP dependent (KATP) channel inhibition partially
restored the contractile response (p<0.05). Elevation of VCAM expression and
aortic structural alternation were observed in each model. SIGNIFICANCE: These
results suggest that the CI model may be an additional tool that could be used to
investigate the mechanisms of vascular hyporesponsiveness in sepsis.
PMID- 26417685
TI - Isolation and characterization of (15Z)-lycopene thermally generated from a
natural source.
AB - (15Z)-Lycopene was prepared by thermal isomerization of (all-E)-lycopene derived
from tomatoes, and isolated by using a series of chromatographies. The fine red
crystalline powder of (15Z)-lycopene was obtained from 556 mg of (all-E)-lycopene
with a yield of 0.6 mg (purity: reversed-phase HPLC, 97.2%; normal-phase HPLC,
>=99.9%), and (1)H and (13)C NMR spectra of the isomer were fully assigned. More
refined computational analyses that considered differences in the energy levels
of the conformers involved in isomerization have also determined the stabilities
of (15Z)-lycopene and other geometric isomers, along with the activation energies
during isomerization from the all-E form. The fine control of conditions for HPLC
separation and an advanced theoretical insight into geometric isomerization have
led to the discovery of the 15Z-isomer generated from a natural source.
PMID- 26417686
TI - Activin A in combination with OP9 cells facilitates development of Flk-1(+)
PDGFRalpha(-) and Flk-1(+) PDGFRalpha(+) hematopoietic mesodermal cells from
murine embryonic stem cells.
AB - Lateral mesoderm-derived hemogenic endothelial cells are known to originate the
definitive hematopoietic lineage in mouse embryogenesis. The developmental
process of the definitive hematopoietic lineage can be recapitulated by inducing
differentiation of mouse embryonic stem (ES) cells in a co-culture system with
OP9 stromal cells. However, the signaling molecules that can modulate the
development of the definitive hematopoietic lineage in the OP9 co-culture system
have yet to be identified. Here we report that activin A enhanced the
hematopoietic potential of endothelial cells derived from ES cells in the OP9 co
culture system. Activin A in combination with OP9 cells augmented development of
Flk-1(+) PDGFRalpha(+) early mesodermal cells and Flk-1(+) PDGFRalpha(-) lateral
mesodermal cells from ES cells. These Flk-1(+) mesodermal cells further
differentiated into CD41(+) endothelial cells, which preferentially possessed
high hematopoietic potential. Furthermore, Flk-1(+) PDGFRalpha(+) cells but not
Flk-1(+) PDGFRalpha(-) cells produced hematopoietic progenitors with a bimodal
pattern when cultured as an aggregate with OP9 cells. Our results suggest that
activin A in combination with OP9 cells facilitates differentiation of ES cells
to Flk-1(+) mesodermal cells, which encompass various precursors that separately
contribute to the development of hematopoietic lineages.
PMID- 26417683
TI - Analysis of TMEFF2 allografts and transgenic mouse models reveals roles in
prostate regeneration and cancer.
AB - BACKGROUND: Previous results from our lab indicate a tumor suppressor role for
the transmembrane protein with epidermal growth factor and two follistatin motifs
2 (TMEFF2) in prostate cancer (PCa). Here, we further characterize this role and
uncover new functions for TMEFF2 in cancer and adult prostate regeneration.
METHODS: The role of TMEFF2 was examined in PCa cells using Matrigel(TM) cultures
and allograft models of PCa cells. In addition, we developed a transgenic mouse
model that expresses TMEFF2 from a prostate specific promoter. Anatomical,
histological, and metabolic characterizations of the transgenic mouse prostate
were conducted. The effect of TMEFF2 in prostate regeneration was studied by
analyzing branching morphogenesis in the TMEFF2-expressing mouse lobes and
alterations in branching morphogenesis were correlated with the metabolomic
profiles of the mouse lobes. The role of TMEFF2 in prostate tumorigenesis in
whole animals was investigated by crossing the TMEFF2 transgenic mice with the
TRAMP mouse model of PCa and analyzing the histopathological changes in the
progeny. RESULTS: Ectopic expression of TMEFF2 impairs growth of PCa cells in
Matrigel or allograft models. Surprisingly, while TMEFF2 expression in the TRAMP
mouse did not have a significant effect on the glandular prostate epithelial
lesions, the double TRAMP/TMEFF2 transgenic mice displayed an increased incidence
of neuroendocrine type tumors. In addition, TMEFF2 promoted increased branching
specifically in the dorsal lobe of the prostate suggesting a potential role in
developmental processes. These results correlated with data indicating an
alteration in the metabolic profile of the dorsal lobe of the transgenic TMEFF2
mice. CONCLUSIONS: Collectively, our results confirm the tumor suppressor role of
TMEFF2 and suggest that ectopic expression of TMEFF2 in mouse prostate leads to
additional lobe-specific effects in prostate regeneration and tumorigenesis. This
points to a complex and multifunctional role for TMEFF2 during PCa progression.
PMID- 26417687
TI - Phosphorylation of Mycobacterium tuberculosis protein tyrosine kinase A PtkA by
Ser/Thr protein kinases.
AB - Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has
inflicted about one third of mankind and claims millions of deaths worldwide
annually. Signalling plays an important role in Mtb pathogenesis and persistence,
and thus represents attractive resource for drug target candidates. Here, we show
that protein tyrosine kinase A (PtkA) can be phosphorylated by Mtb endogenous
eukaryotic-like Ser/Thr protein kinases (eSTPKs). Kinase assays showed that PknA,
PknD, PknF, and PknK can phosphorylate PtkA in dose- and time-dependent manner.
Enzyme kinetics suggests that PknA has the highest affinity and enzymatic
efficiency towards PtkA. Furthermore, protein-protein interaction assay in
surrogate host showed that PtkA interacts with multi-eSTPKs in vivo, including
PknA. Lastly, we show that PtkA phosphorylation by eSTPKs occurs on threonine
residues and may effect tyrosine phosphorylation levels and thus PtkA activity in
vitro. These results demonstrate that PtkA can serve as a substrate to many
eSTPKs and suggests that's its activity can be regulated.
PMID- 26417688
TI - Yhhu4488, a novel GPR40 agonist, promotes GLP-1 secretion and exerts anti
diabetic effect in rodent models.
AB - G protein-coupled receptor 40 (GPR40) is predominantly expressed in pancreatic
beta-cells and activated by long-chain fatty acids. GPR40 has drawn considerable
interest as a potential therapeutic target for type 2 diabetes mellitus (T2DM)
due to its important role in enhancing glucose-stimulated insulin secretion
(GSIS). Encouragingly, GPR40 is also proven to be highly expressed in glucagon
like peptide-1 (GLP-1)-producing enteroendocrine cells afterwards, which opens a
potential role of GPR40 in enhancing GLP-1 secretion to exert additional anti
diabetic efficacy. In the present study, we discovered a novel GPR40 agonist,
yhhu4488, which is structurally different from other reported GPR40 agonists.
Yhhu4488 showed potent agonist activity with EC50 of 49.96 nM, 70.83 nM and 58.68
nM in HEK293 cells stably expressing human, rat and mouse GPR40, respectively.
Yhhu4488 stimulated GLP-1 secretion from fetal rat intestinal cells (FRIC) via
triggering endogenous calcium store mobilization and extracellular calcium
influx. The effect of yhhu4488 on GLP-1 secretion was further confirmed in type 2
diabetic db/db mice. Yhhu4488 exhibited satisfactory potency in in vivo studies.
Single administration of yhhu4488 improved glucose tolerance in SD rats. Chronic
administration of yhhu4488 effectively decreased fasting blood glucose level,
improved beta-cell function and lipid homeostasis in type 2 diabetic ob/ob mice.
Taken together, yhhu4488 is a novel GPR40 agonist that enhances GLP-1 secretion,
improves metabolic control and beta-cell function, suggesting its promising
potential for the treatment of type 2 diabetes.
PMID- 26417689
TI - Exposure to 3,3',5-triiodothyronine affects histone and RNA polymerase II
modifications, but not DNA methylation status, in the regulatory region of the
Xenopus laevis thyroid hormone receptor betaAlpha gene.
AB - Thyroid hormones (THs) play a critical role in amphibian metamorphosis, during
which the TH receptor (TR) gene, thrb, is upregulated in a tissue-specific
manner. The Xenopus laevis thrb gene has 3 TH response elements (TREs) in the 5'
flanking regulatory region and 1 TRE in the exon b region, around which CpG sites
are highly distributed. To clarify whether exposure to 3,3',5-triiodothyronine
(T3) affects histone and RNA polymerase II (RNAPII) modifications and the level
of DNA methylation in the 5' regulatory region, we conducted reverse
transcription-quantitative polymerase chain reaction, bisulfite sequencing and
chromatin immunoprecipitation assay using X. laevis cultured cells and
premetamorphic tadpoles treated with or without 2 nM T3. Exposure to T3 increased
the amount of the thrb transcript, in parallel with enhanced histone H4
acetylation and RNAPII recruitment, and probably phosphorylation of RNAPII at
serine 5, in the 5' regulatory and exon b regions. However, the 5' regulatory
region remained hypermethylated even with exposure to T3, and there was no
significant difference in the methylation status between DNAs from T3-untreated
and -treated cultured cells or tadpole tissues. Our results demonstrate that
exposure to T3 induced euchromatin-associated epigenetic marks by enhancing
histone acetylation and RNAPII recruitment, but not by decreasing the level of
DNA methylation, in the 5' regulatory region of the X. laevis thrb gene.
PMID- 26417690
TI - AGPAT2 deficiency impairs adipogenic differentiation in primary cultured
preadipocytes in a non-autophagy or apoptosis dependent mechanism.
AB - AIMS: Mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) result
in lipodystrophy, insulin resistance and diabetes. Autophagy is required for
normal adipogenesis and adipose tissue development. The aim of this study was to
determine whether impaired autophagy or excessive cell death underlie the
adipogenic inability of Agpat2(-/-) mice preadipocytes. METHODS: Preadipocytes
were isolated from interscapular brown adipose tissue (BAT) of Agpat2(-/-) and
Agpat2(+/+) newborn mice and cultured/differentiated in vitro. Intracellular
lipids were quantified by oil red O staining. Cell death was assessed by lactate
dehydrogenase (LDH) activity. Apoptosis and autophagy regulatory factors were
determined at the mRNA and protein level with Real-time PCR, immunoblot and
immunofluorescence. RESULTS: Adipogenically induced Agpat2(-/-) preadipocytes had
fewer lipid-loaded cells and lower levels of adipocyte markers than wild type
preadipocytes. Before adipogenic differentiation, autophagy-related proteins
(ATGs) ATG3, ATG5-ATG12 complex, ATG7 and LC3II were increased but autophagic
flux was reduced, as suggested by increased p62 levels, in Agpat2(-/-)
preadipocytes. Adipogenic induction increased LDH levels in the culture media in
Agpat2(-/-) preadipocytes but no differences were observed in the activation of
Caspase 3 or in markers of autophagic flux. CONCLUSIONS: AGPAT2 is required for
in vitro adipogenesis of mouse preadipocytes. Autophagy defects or apoptosis are
not involved in the adipogenic failure of Agpat2(-/-) preadipocytes.
PMID- 26417691
TI - Angiopoietin-like 4 enhances metastasis and inhibits apoptosis via inducing bone
morphogenetic protein 7 in colorectal cancer cells.
AB - Angiopoietin-like 4 (ANGPTL4), a secretory glycoprotein, plays an important role
in cancer metastasis. In the present study, we aim to investigate the roles and
mechanisms of ANGPTL4 in the regulation of colorectal cancer metastasis. We found
that expression level of ANGPTL4 was increased in colorectal cancer tissues,
compared with that in normal tissues. Moreover, liver metastasis was
significantly associated with higher expression of ANGPTL4. In vitro studies
further showed that overexpression of ANGPTL4 enhanced cell migration, invasion
and inhibited apoptosis. At the molecular level, ANGPTL4 overexpression resulted
in an up-regulation of bone morphogenetic protein 7 (BMP7). Indeed, knockdown of
BMP7 by small interfering RNA (siRNA) oligos reversed the roles of ANGPTL4
overexpression in HCT116 cells. Finally, in vivo studies further confirmed the
metastatic roles of ANGPTL4 by inducing BMP7. Therefore, our study demonstrated
that ANGPTL4 might promote metastasis and might inhibit apoptosis of colorectal
cancer cells by up-regulation of BMP7.
PMID- 26417693
TI - Ovarian infertility is associated with cardiovascular disease risk factors in
later life: A Japanese cross-sectional study.
AB - OBJECTIVES: This study aimed to clarify the association between ovarian
infertility and cardiovascular disease risk factors in later life in Japanese
women. STUDY DESIGN: The Japan Nurses' Health Study (JNHS) is a cohort study of
Japanese women's health. Data from the JNHS baseline survey (n = 49,927) between
2001 and 2007 were used in a cross-sectional, retrospective analysis. A total of
44,601 women were classified into three categories: ovarian infertility group
(n=1167), other infertility group (n = 4619), and no infertility group (n =
38,815). Logistic regression analysis compared with the no infertility group was
performed. MAIN OUTCOME MEASURES: Age-adjusted odds ratios (ORs) and
multivariable-adjusted ORs for hypertension, hypercholesterolemia, and diabetes
mellitus (DM). RESULTS: The prevalence of obese women (BMI >= 25) who were < 45
years old in the ovarian infertility group was significantly higher compared with
that in the other groups. Women in the ovarian infertility group were at risk for
hypertension at >= 45 years old (age-adjusted OR: 1.65%, confidence interval
[CI]: 1.23-2.21); for hypercholesterolemia at < 45 and >= 45 years old (age
adjusted OR: 1.42, 95% CI: 1.06-1.88 at < 45 years; age-adjusted OR: 1.39, 95%
CI: 1.06-1.81 at >= 45 years); and for DM at < 45 years old (age-adjusted OR:
2.92, 95% CI: 1.57-5.46). CONCLUSIONS: Japanese women with ovarian infertility
(most women have polycystic ovary syndrome) are at high risk of hypertension from
45 years of age, hypercholesterolemia at all ages, and diabetes mellitus (DM)
before 45 years old.
PMID- 26417692
TI - The role and regulation of Moraxella catarrhalis-induced human beta-defensin 3
expression in human pulmonary epithelial cells.
AB - BACKGROUND: Bacterial colonisation with Moraxella catarrhalis may partly sustain
chronic inflammation in the lower airways of patients with chronic obstructive
pulmonary disease (COPD). In addition, this bacterium causes infectious
exacerbations of COPD, which often necessitate treatment with antibiotics.
Antimicrobial peptides are the body's own antibiotic substances with bactericidal
and bacteriostatic, as well as immunomodulatory function. In particular, human
beta-defensin 3 (hBD-3) exerts an antimicrobial effect against an extraordinarily
broad spectrum of pathogens. We therefore investigated the role of hBD-3 in
infections of pulmonary epithelial cells with M. catarrhalis. METHODS: The
antimicrobial activity of hBD-3 vs. M. catarrhalis was evaluated in an
antimicrobial susceptibility assay. We analyzed hBD-3 secretion of M. catarrhalis
infected pulmonary epithelial cells using ELISA. The role of M. catarrhalis
specific virulence factors, toll-like receptors (TLR) 2 and 4, MAPK pathways, and
transcription factors AP-1 and NF-kappaB in the induction and regulation of hBD-3
expression were explored with specific inhibitors, small interference RNA,
Western Blot, and chromatin immunoprecipitation (ChIP) assays. RESULTS: HBD-3
exhibited a strong bactericidal effect against M. catarrhalis. M. catarrhalis
induced hBD-3 expression in pulmonary epithelial cells, which was dependent on M.
catarrhalis membranous lipoolygosaccharide (LOS), while the surface proteins
UspA1 and UspA2 were not involved. Gene silencing of TLR2, but not TLR4, led to a
reduced hBD-3 secretion after stimulation with M. catarrhalis or M. catarrhalis
LOS. Inhibition of MAPKs ERK1/2 and JNK, but not p38, reduced hBD-3 secretion.
HBD-3 expression was mediated through the recruitment of AP-1 to the hBD-3 gene
promoter and was independent of NF-kappaB. CONCLUSION: The immune response of
pulmonary epithelial cells towards M. catarrhalis involves secretion of hBD-3,
which has a bactericidal effect against this pathogen. Binding of M. catarrhalis
virulence factor LOS to TLR2 causes an ERK1/2- and JNK-dependent induction of AP
1-related transcription of the hBD-3 gene, resulting in the production and
secretion of hBD-3.
PMID- 26417694
TI - Homogeneous Immunochemical Assay on the Lateral Flow Strip for Measurement of
DNase I Activity.
AB - Deoxyribonuclease I (DNase I) is an important enzyme that cleaves both double
stranded and single-stranded DNA at their phosphate backbone. DNase I is a useful
biomarker. Previous studies have shown that patients with prostate cancer and
systemic lupus erythematosus exhibit reduced DNase I activity, and patients with
myocardial infarction exhibit increased DNase I activity. Current methods of
measuring DNase I relies either on an immunochemical assay, which requires
multiple washing steps, or on a single radial enzyme diffusion assay, which
requires a long digestion time and an expensive fluorescence detection system. We
have developed a lateral flow immunochemical assay for the measurement of DNase I
activity on the test strip. The assay utilized a dually labeled double-stranded
DNA as the reporter probe. The biotin-labeled terminal of the probe bound to the
streptavidin immobilized on the lateral flow test strip, and the fluorescein
labeled terminal bound to the antibody-conjugated gold nanoparticles, resulting
in a visible test line. The presence of DNase I would cleave the reporter probe
and lead to reduced test line intensity. Using the DNase I test strip, we have
successfully measured the DNase I activity and determined the factors that
influence the sensitivity and linear dynamic range of the assay. We have also
investigated the conditions that inhibited the DNase I activity. The combined
advantage of a wash-free assay format and colorimetric readout would make the
lateral flow DNase I test strip a suitable platform for point-of-care
diagnostics.
PMID- 26417695
TI - Iron Status of Cats with Chronic Kidney Disease.
AB - BACKGROUND: Iron deficiency is a proposed mechanism for the anemia that occurs in
cats with chronic kidney disease (CKD). Minimal research investigating the iron
status of these cats has been performed. OBJECTIVE: To compare indicators of iron
status in cats with CKD versus healthy cats and cats with nonrenal illness (NRI).
To compare indicators of iron status in anemic versus nonanemic cats with CKD.
ANIMALS: Thiry-nine client or employee owned healthy cats, 40 cats with CKD and
34 cats with NRI included. METHODS: Exclusion criteria included prior iron or
erythropoiesis stimulating agent administration, blood transfusion, or concurrent
CKD and NRI. Complete blood counts, serum chemistries, serum iron concentrations,
total iron binding capacity (TIBC), and ferritin concentrations were measured and
percent transferrin saturation (TSAT) calculated on all cats. Data were analyzed
using nonparametric statistical testing. RESULTS: No statistically significant
differences were detected among groups for iron concentration (P = .50), ferritin
concentration (P = .47), or TSAT (P = .19). TIBC was significantly lower in CKD
(median 262 MUg/dL; IQR 233-302; range 165-488) versus healthy cats (median 316
MUg/dL; IQR 272-345, range 196-464); (P = .0030). When comparing anemic
(hemoglobin <9.5 g/dL) versus nonanemic cats with CKD, TSAT was significantly
lower (P = .033) in anemic (median 20.2%; IQR 17.8-34.5; range 17.6-35.9)
compared to nonanemic (median 29.0%; IQR 25.5-44.1; range 11.5-94.4). No
statistically significant differences found for ferritin concentration (P = .94),
iron concentration (P = .21) or TIBC (P = .97). CONCLUSIONS AND CLINICAL
IMPORTANCE: These results indicate that an iron deficient state exists in anemic
cats with CKD and is more likely functional rather than absolute.
PMID- 26417696
TI - Aspartic acid racemization reveals a high turnover state in knee compared with
hip osteoarthritic cartilage.
AB - OBJECTIVE: We investigated tissue turnover in healthy and osteoarthritic
cartilage. We challenge long held views that osteoarthritis (OA) is dominated by
a similar turnover process in all joints and present evidence that hip and knee
cartilage respond very differently to OA. METHODS: d- and l-Aspartate (Asp) were
quantified for whole cartilage, collagen and non-collagenous components of
cartilage obtained at the time of joint replacement. We computed the Asp
racemization ratio (Asp-RR = d/d + l Asp), reflecting the proportion of old to
total protein, for each component. RESULTS: Compared with hip OA, knee OA
collagen fibrils (P < 0.0001), collagen (P = 0.007), and non-collagenous proteins
(P = 0.0003) had significantly lower age-adjusted mean Asp-RRs consistent with
elevated protein synthesis in knee OA. Knee OA collagen had a mean
hydroxyproline/proline (H/P) ratio of 1.2 consistent with the presence of type
III collagen whereas hip OA collagen had a mean H/P ratio of 0.99 consistent with
type II collagen. Based on Asp-RR, the relative age was significantly different
in knee and hip OA (P < 0.0005); on average OA knees were estimated to be 30 yrs
'younger', and OA hips 10 yrs 'older' than non-OA. CONCLUSIONS: The metabolic
response to OA was strikingly different by joint site. Knee OA cartilage evinced
an anabolic response that appeared to be absent in hip OA cartilage. These
results challenge the long held view that OA cartilage is capable of only minimal
repair and that collagen loss is irreversible.
PMID- 26417697
TI - Plasma bioavailability and regional brain distribution of polyphenols from
apple/grape seed and bilberry extracts in a young swine model.
AB - SCOPE: The pharmacokinetics, bioavailability, and regional brain distribution of
polyphenols from apple-grape seed extract (AGSE) mixture and bilberry extract
were studied after 3 weeks of dosing in weanling pigs. MATERIALS AND METHODS:
Weanling piglets were treated for 3 weeks with extracts of (AGSE) or bilberry
extracts, using a physiological (27.5 mg/kg) or supplement (82.5 mg/kg) dose. A
24-h pharmacokinetic study was conducted and brain tissue was harvested. Major
flavan-3-ol and flavonol metabolites including catechin-O-beta-glucuronide,
epicatechin-O-beta-glucuronide, 3'O-methyl-catechin-O-beta-glucuronide, 3'O
methyl-epicatechin-O-beta-glucuronide, quercetin-O-beta-glucuronide, and O-methyl
quercetin-O-beta-glucuronide were analyzed in plasma, urine, and regional brain
extracts from AGSE groups. Anthocyanidin-O-galactosides and O-glucosides of
delphinidin (Del), cyanidin (Cyn), petunidin (Pet), peonidin (Peo), and malvidin
(Mal) were analyzed in plasma, urine, and brain extracts from bilberry groups.
CONCLUSION: Significant plasma dose-dependence was observed in flavan-3-ol
metabolites of the AGSE group and in Mal, Del and Cyn galactosides and Pet, Peo,
and Cyn glucosides of the bilberry groups. In the brain, a significant dose
dependence was found in the cerebellum and frontal cortex in all major flavan-3
ol metabolites. All anthocyanidin glycosides, except for delphinidin, showed a
dose-dependent increase in the cerebellum.
PMID- 26417698
TI - In ovo administration of copper nanoparticles and copper sulfate positively
influences chicken performance.
AB - BACKGROUND: Copper (Cu) is a key trace mineral involved in a variety of
physiological processes, and is commonly used in poultry production. However,
regardless of the inclusion level the majority of Cu is excreted with poultry
faeces. We hypothesise that in ovo administration will allow for better
utilisation of Cu during embryo development than when supplied post-natally with
feed to growing chickens. Thus, the objective of this study was to evaluate
effects of in ovo administration of NanoCu and copper sulfate (CuSO4 ) on broiler
chicken performance. RESULTS: The study showed the positive influences of Cu
nanoparticles and CuSO4 on broiler chickens performance. Body weight, at the end
of the rearing period (day 42) was significantly higher in NanoCu (2206 g) and
CuSO4 (2402 g) groups compared to the control group (2000 g). Both treatment
groups had significantly lower feed conversion rate and mortality, and higher
percentage of breast and leg muscles in the carcass versus control. CONCLUSION:
The in ovo application of Cu colloids may ensure an efficient penetration of Cu
into the embryonic tissue with long lasting effects on postnatal growth. The
method may provide a successful alternative to using Cu as a feed additive. (c)
2015 Society of Chemical Industry.
PMID- 26417699
TI - Prognostic value of residual pulmonary congestion at discharge assessed by lung
ultrasound imaging in heart failure.
AB - AIMS: Residual pulmonary congestion at discharge is associated with poor
prognosis in heart failure (HF), but its quantification through physical
examination is challenging. Ultrasound imaging of lung comets (B-lines) could
improve congestion evaluation. The aim of this study was to assess the short-term
prognostic value of B-lines after discharge from HF hospitalisation compared with
other indices of haemodynamic congestion (BNP, E/e', and inferior vena cava
diameter) or clinical status (NYHA class). METHODS AND RESULTS: Sixty consecutive
HF inpatients underwent clinical examination, echocardiography, and lung
ultrasound at discharge, independently of, and in addition to routine management
by the attending physicians. The median B-line count was 8.5 (5-34). Three-month
event-free survival for the primary endpoint (all-cause death or HF
hospitalisation) was 27 +/- 10% in patients with >=30 B-lines and 88 +/- 5% in
those with <30 B-lines (P < 0.0001). In a multivariable model, >=30 B-lines
significantly predicted the combined endpoint (hazard ratio 5.66, 95% confidence
interval 1.74-18.39, P = 0.04), along with NYHA >=III and inferior vena cava
diameter, while other indirect measures of congestion (BNP and E/e' >=15) were
not retained in the model; furthermore >=30 B-lines independently also predicted
the secondary outcomes (HF hospitalisation and death). Importantly, B-line
addition to NYHA class and BNP was associated with improved risk classification
(integrated discrimination improvement 15%, P = 0.02; continuous net
reclassification improvement 65%, P = 0.03). CONCLUSION: Residual pulmonary
congestion at discharge, as assessed by a B-line count >=30, is a strong
predictor of outcome. Lung ultrasonography may represent a useful tool to
identify and monitor congestion and optimize therapy during and/or after
hospitalisation for HF, which should be further validated in multicentre studies.
PMID- 26417700
TI - Serum levels of phytoestrogens as biomarkers of intake in Mexican women.
AB - Phytoestrogens have generated interest in human health in view of their potential
effect to reduce the risk of developing chronic diseases. Serum levels of
phytoestrogens have been proposed as an alternative to measure the exposure of
phytoestrogens. We evaluated the use of serum as a biomarker of phytoestrogen's
intake in healthy women. Phytoestrogens in serum (luteolin, kaempferol, equol,
biochanin A, formononetin, quercetin, naringenin, coumestrol,
secoisolariciresinol, genistein, matairesinol, enterolactone, enterodiol,
daidzein, glycitein and resveratrol) were analyzed by HPLC-ESI-MS. Subjects were
asked to recall all foods and beverages consumed the previous 24 h. Association
of dietary intake and serum concentrations was performed by Spearman correlation.
Correlations were found for naringenin (r = 0.47, p < 0.001), luteolin (r = 0.4 p
< 0.001), genistein (r = 0.32, p < 0.01) enterolactone (r = 0.35, p = 0.0553),
coumestrol (r = 0.26, p = 0.0835) and resveratrol (r = 0.29, p = 0.0517). Serum
levels as biomarkers of intake along with a 24-h recall would be useful in order
to investigate the relationship between phytoestrogens and health.
PMID- 26417701
TI - Variability in quality of chest compressions provided during simulated cardiac
arrest across nine pediatric institutions.
AB - AIM: The variability in quality of CPR provided during cardiac arrest across
pediatric institutions is unknown. We aimed to describe the degree of variability
in the quality of CPR across 9 pediatric institutions, and determine if
variability across sites would be affected by Just-in-Time CPR training and/or
visual feedback during simulated cardiac arrest. METHODS: We conducted secondary
analyses of data collected from a prospective, multi-center trial. Participants
were equally randomized to either: (1) No intervention; (2) Real-time CPR visual
feedback during cardiac arrest or (3) Just-in-Time CPR training. We report the
variability in median chest compression depth and rate across institutions, and
the variability in the proportion of 30-s epochs of CPR meeting 2010 American
Heart Association guidelines for depth and rate. RESULTS: We analyzed data from
528 epochs in the no intervention group, 552 epochs in the visual feedback group,
and 525 epochs in the JIT training group. In the no intervention group,
compression depth (median range 22.2-39.2mm) and rate (median range 116.0-147.6
min(-1)) demonstrated significant variability between study sites (p<0.001). The
proportion of compressions with adequate depth (0-11.5%) and rate (0-60.5%) also
varied significantly across sites (p<0.001). The variability in compression depth
and rate persisted despite use of real-time visual feedback or JIT training
(p<0.001). CONCLUSION: The quality of CPR across multiple pediatric institutions
is variable. Variability in CPR quality across institutions persists even with
the implementation of a Just-in-Time training session and visual feedback for CPR
quality during simulated cardiac arrest.
PMID- 26417702
TI - Canadian Guidelines for the use of targeted temperature management (therapeutic
hypothermia) after cardiac arrest: A joint statement from The Canadian Critical
Care Society (CCCS), Canadian Neurocritical Care Society (CNCCS), and the
Canadian Critical Care Trials Group (CCCTG).
PMID- 26417703
TI - Hope and perceptions of parental role among parents assessed as maltreating their
children.
AB - The present study is anchored in the view that hope is a resource that fosters
better coping and parenting. It examines the self-perceived hope and parental
role of parents whom the welfare services in Israel have assessed as maltreating
their children. The parents were recruited in 2010 through facilities for
maltreated children. The study sample consisted of 262 parents (68.4% response
rate), divided into those who had at least one child removed from home and those
whose children were all at home. Both groups of parents reported moderately high
basic and family hope and sense of pathways and agency, and moderate perceived
parental role, with no significant group differences. Differences were found,
however, in the role of hope in mediating between parents' sociodemographic
features and their perceived parental role. The mediation was more substantial
among the parents whose children were at home and differed in content. Only among
parents whose children were at home did religiosity (beta = 0.20, P < 0.05) and
living with a partner (beta = 0.18, P < 0.05) lead to greater hope, which
increased the perceived parental role. Moreover, the findings underscore the lack
of role of family hope and sense of agency among parents whose children were not
at home. In both the groups, higher income led to greater hope (beta = 0.18, P <
0.05 for at home; beta = 0.16, P < 0.05 for in placement), which increased the
self-perceived parental role but the mediation was effected differently. The
findings suggest that professionals working with parents who maltreat their
children can use the parents' hope as a resource to help them improve their
parenting, especially where the child was removed from home.
PMID- 26417705
TI - The impact of cardiopulmonary exercise testing on patients over the age of 80
undergoing elective colorectal cancer surgery.
AB - AIM: Advanced age and occult cardiorespiratory disease are associated with
increased morbidity and mortality following surgery. Cardiopulmonary exercise
testing (CPET) may allow the identification of high-risk patients and facilitate
planned postoperative critical care support. The aim of this study was to
determine whether preoperative CPET in patients aged over 80 undergoing elective
colorectal cancer resection was associated with improved outcome. METHOD: All
patients aged 80 years and above undergoing elective colorectal cancer resection
between 1 March 2011 and 1 September 2013 were retrospectively analysed. Referral
for CPET testing was at the discretion of the operating surgeon. Postoperative
critical care unit (CCU) admission was based upon the CPET results. RESULTS:
Ninety-four patients were identified, of whom 48 underwent CPET testing. The CPET
group were significantly older than the non-CPET group (85 vs 83 years, P = 0.04)
and were more likely to have a planned admission to CCU postoperatively (P <
0.0001). Despite the increased use of CCU resources, the overall CCU length of
stay (LOS) in the CPET group did not differ from the non-CPET group, but the non
CPET group had a higher proportion of Level-3 care. There were no differences in
the incidence of unplanned CCU admission between the CPET and the non-CPET group
(P = 0.23). There were no differences in overall LOS between the two groups (P =
0.42). There was no difference in mortality (P = 0.11), overall complications (P
= 0.53) or severe complications (P = 0.3). CONCLUSION: Preoperative CPET testing
in patients aged over 80 undergoing elective colorectal cancer resection allows
identification of higher-risk patients and mitigation of risk by preemptive
admission to a CCU. This stratification allows equivalent results to be achieved
in high- and low-risk elderly patients undergoing colorectal surgery.
PMID- 26417706
TI - Startup of electrophoresis in a suspension of colloidal spheres.
AB - The transient electrophoretic response of a homogeneous suspension of spherical
particles to the step application of an electric field is analyzed. The electric
double layer encompassing each particle is assumed to be thin but finite, and the
effect of dynamic electroosmosis within it is incorporated. The momentum equation
for the fluid outside the double layers is solved through the use of a unit cell
model. Closed-form formulas for the time-evolving electrophoretic and settling
velocities of the particles in the Laplace transform are obtained in terms of the
electrokinetic radius, relative mass density, and volume fraction of the
particles. The time scale for the development of electrophoresis and
sedimentation is significantly smaller for a suspension with a higher particle
volume fraction or a smaller particle-to-fluid density ratio, and the
electrophoretic mobility at any instant increases with an increase in the
electrokinetic particle radius. The transient electrophoretic mobility is a
decreasing function of the particle volume fraction if the particle-to-fluid
density ratio is relatively small, but it may increase with an increase in the
particle volume fraction if this density ratio is relatively large. The particle
interaction effect in a suspension on the transient electrophoresis is much
weaker than that on the transient sedimentation of the particles.
PMID- 26417704
TI - Genome-wide association meta-analysis identifies five modifier loci of lung
disease severity in cystic fibrosis.
AB - The identification of small molecules that target specific CFTR variants has
ushered in a new era of treatment for cystic fibrosis (CF), yet optimal,
individualized treatment of CF will require identification and targeting of
disease modifiers. Here we use genome-wide association analysis to identify
genetic modifiers of CF lung disease, the primary cause of mortality. Meta
analysis of 6,365 CF patients identifies five loci that display significant
association with variation in lung disease. Regions on chr3q29 (MUC4/MUC20; P=3.3
* 10(-11)), chr5p15.3 (SLC9A3; P=6.8 * 10(-12)), chr6p21.3 (HLA Class II; P=1.2 *
10(-8)) and chrXq22-q23 (AGTR2/SLC6A14; P=1.8 * 10(-9)) contain genes of high
biological relevance to CF pathophysiology. The fifth locus, on chr11p12-p13
(EHF/APIP; P=1.9 * 10(-10)), was previously shown to be associated with lung
disease. These results provide new insights into potential targets for modulating
lung disease severity in CF.
PMID- 26417707
TI - Inflammatory response and endothelial dysfunction in the hearts of mice co
exposed to SO2 , NO2 , and PM2.5.
AB - SO2 , NO2 , and PM2.5 are typical air pollutants produced during the combustion
of coal. Increasing evidence indicates that air pollution has contributed to the
development and progression of heart-related diseases over the past decades.
However, little experimental data and few studies of SO2 , NO2 , and PM2.5 co
exposure in animals exist; therefore, the relevant mechanisms underlying this
phenomenon are unclear. An important characteristic of air pollution is that co
exposure persists at a low concentration throughout a lifetime. In the present
study, we treated adult mice with SO2 , NO2 , and PM2.5 at various concentrations
(0.5 mg/m3 SO2 , 0.2 mg/m3 NO2 6 h/d, with intranasal instillation of 1 mg/kg
PM2.5 every other day during these exposures; or 3.5 mg/m3 SO2 , 2 mg/m3 NO2 6
h/d, and 10 mg/kg PM2.5 for 28 d). Blood pressure (BP), heart rate (HR),
histopathological damage, and inflammatory and endothelial cytokines in the heart
were assessed. The results indicate that co-exposure caused endothelial
dysfunction by elevating endothelin-1 (ET-1) expression and repressing the
endothelial nitric oxide synthase (eNOS) level as well as stimulating the
inflammatory response by increasing the levels of cyclooxygenase-2 (COX-2),
inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha)
and interleukin-6 (IL-6). Additionally, these alterations were confirmed by
histological staining. Furthermore, we observed decreased BP and increased HR
after co-exposure. Our results indicate that co-exposure to SO2 , NO2 , and PM2.5
may be a major risk factor for cardiac disease and may induce injury to the
hearts of mammals and contribute to heart disease. (c) 2015 Wiley Periodicals,
Inc. Environ Toxicol 31: 1996-2005, 2016.
PMID- 26417709
TI - Relative age effect: implications for effective practice.
AB - Physical and psychological differences related to birthdate amongst athletes of
the same selection year have been characterised as the "relative age effects"
(RAEs). RAEs have been identified in a variety of sports, both at youth and adult
level, and are linked with dropout of athletes and a reduction of the talent
pool. This study examined the existence, mechanisms and possible solutions to
RAEs using qualitative methodology. Seven experts in the field of talent
identification and development were interviewed. Inductive analysis of the data
showed that, while there was mixed evidence for the existence of RAEs across
sports, the eradication of RAEs was attributed to controllable features of the
development environment. The factors reported included the structure of
"categories" used to group athletes within the sport (e.g. age, weight, size,
skills), recognition and prioritisation of long-term development over "short term
win focus." Education of relevant parties (e.g. coaches, scouts, clubs) about
RAEs and the nature of "talent" within a long-term context was suggested, along
with careful consideration of the structure of the development environment (e.g.
delayed selection, provision for late developers, focus on skills not results,
use of challenge). Implications for research and practice are discussed.
PMID- 26417708
TI - Deoxynivalenol, but not E. coli lipopolysaccharide, changes the response pattern
of intestinal porcine epithelial cells (IPEC-J2) according to its route of
application.
AB - The porcine intestinal epithelium is a primary target for mycotoxin
deoxynivalenol (DON) and lipopolysaccharides (LPS). Although epithelial cells are
exposed to these toxins mainly from the luminal-chyme compartment an exposure
from the blood side resulting from systemic absorption cannot be excluded. Thus,
we investigated the effect of DON and LPS, alone or combined, on porcine
intestinal epithelial cells IPEC-J2 on a transcriptional, translational and
functional level when administered either from apical or basolateral. IPEC-J2
cells were cultured on 12-well inserts in complete medium at 5% CO2 and 39
degrees C and subjected to following treatments: control (CON), 2000 ng/mL DON, 1
MUg/mL LPS or DON+LPS for 72 h, either from apical or basolateral.
Transepithelial electrical resistance (TEER), protein and IL-8 content were
measured and microarray analysis, qRT-PCR (IL-8, zonula occludens-1 ZO-1, beta
actin), Western Blot (ZO-1, beta-actin) and immunofluorescence (ZO-1) were
performed. Data of at least three independent experiments were analysed with
ANOVA and Dunnett's post hoc test. Basolateral DON resulted in significantly
lower cell counts (p<0.05) with larger cells (p<0.01), whereas apical DON reduced
total (p<0.001) and specific protein content (IL-8 content CON vs. DON: 2378 pg/3
mL vs. 991 pg/3 mL; p<0.001). Transcripts of beta-actin and ZO-1 were
significantly upregulated in response to DON, irrespective of direction, whereas
IL-8 mRNA remained unaffected. However, ZO-1 spatial distribution in the tight
junction and its function (TEER) were detrimentally affected by basolateral DON
only. In conclusion, direction of DON exposure affected IPEC-J2 differently on a
translational and functional level, but was mainly inconsequential on a
transcriptional level.
PMID- 26417710
TI - Left-colon antegrade enema (LACE): Long-term experience with the Macedo-Malone
approach.
AB - AIMS: We evaluated the long-term results with a left antegrade continence enema
(LACE) approach: "Macedo-Malone (MM) procedure" to define parameters such as
clinical durability of the technique and patients' compliance with the method.
METHODS: We reviewed the medical records of all patients that underwent the MM
procedure in our institution since 2001 and conducted a telephonic interview to
investigate the use of the enema and satisfaction with the procedure. RESULTS:
Thirty-five MM procedures were performed, but eight patients lost to follow-up
were excluded. Fifteen patients (55%) were female. Myelomeningocele was the
clinical diagnoses in 25 (93%). Mean age at surgery was 9 years (3-27 years) and
mean follow-up was 75 months (median: 56 months). The indication for LACE was
clinically intractable constipation with fecal leakage. Most patients still used
the stoma regularly to do the enema (74%). Mean washout time was 27 min (2-90
min). The revision rate due to stenosis was 22.2% (6/27) and all underwent
suprafascial revision. We performed one classical MACE by infrafascial approach
as a salvage procedure. Overall reoperation rate was 25.8% and fecal continence
was 89%. There were no reports of leakage through the stoma. Among patients who
still used the stoma, 74% were satisfied with surgery and would strongly
recommend the procedure to another patient. CONCLUSIONS: The MM procedure is a
straightforward procedure, which can be performed in 15-20 min, avoids additional
entero-entero anastomosis, precludes the use of the appendix, and has shown
comparable results to either "classical" MACE or other LACE variants. Neurourol.
Urodynam. 36:111-115, 2017. (c) 2015 Wiley Periodicals, Inc.
PMID- 26417711
TI - Reducing anxiety during conscious surgery - A patient survey.
PMID- 26417713
TI - A Survey on Turkish nursing students' perception of clinical learning environment
and its association with academic motivation and clinical decision making.
AB - BACKGROUND: Nursing education is a process that includes theoretical and
practical learning and requires the acquisition of theoretical knowledge and
skill. Nursing students need a good clinical practice environment in order to
apply their knowledge and skills due to the fact that the clinical practice
settings play an important role in the nursing profession. OBJECTIVES: This study
was carried out in an effort to explore nursing students' perception of the
clinical learning environment and its association with academic motivation and
clinical decision making. DESIGN: A descriptive survey design was used. SETTING:
This study was conducted in Giresun University in Turkey. PARTICIPANTS:
Participants were second-, third- and fourth-year undergraduate students (n=222)
in the Bachelor of Nursing Science Degree in the academic spring term of 2014
2015. METHODS: The data was collected using the 'Clinical Learning Environment
Scale', the 'Academic Motivation, and the 'The Clinical Decision Making in
Nursing Scale'. RESULTS: Of the respondents in this study, 45% of the students
were second class, 30.6% of the students were third class and 24.3% of the
students were fourth class. There was a statistically significant positive
correlation found between the clinical learning environment and the nursing
students' academic motivation (r=0.182, p<.05). However, there was no correlation
between the clinical learning environment and clinical decision making (r=0.082,
p>.05). CONCLUSION: One of the prerequisites for the training of qualified
students is to provide nursing students with a qualified clinical environment. It
was found that nursing students' academic motivation increased as the quality of
their clinical learning environment improved.
PMID- 26417714
TI - Northern Ireland and 'The Troubles', outlining an innovative approach to
nursing/midwifery student teaching and module evaluation.
AB - This discussion paper outlines an approach to developing and evaluating an
educative programme primarily delivered by lay 'citizen trainers' in educating
student nurses, and student midwives to the impact of and experience of extended
and extensive civil unrest within their communities ('the Troubles' ). This is
drawn from experience within the Northern Ireland 'Troubles' and all of the
citizen trainers were directly affected physically/psychologically. The programme
was intended to both educate but primarily to help facilitate student nurses and
student midwives to better understanding to experience and context and to more
effective care delivery to those affected by/damaged by 'the Troubles'.
Evaluation of the teaching and learning by the students was significantly
positive.
PMID- 26417715
TI - Identification of active elementary flux modes in mitochondria using selectively
permeabilized CHO cells.
AB - Metabolic compartmentation is a key feature of mammalian cells. Mitochondria are
the powerhouse of eukaryotic cells, responsible for respiration and the TCA
cycle. We accessed the mitochondrial metabolism of the economically important
Chinese hamster ovary (CHO) cells using selective permeabilization. We tested key
substrates without and with addition of ADP. Based on quantified uptake and
production rates, we could determine the contribution of different elementary
flux modes to the metabolism of a substrate or substrate combination. ADP
stimulated the uptake of most metabolites, directly by serving as substrate for
the respiratory chain, thus removing the inhibitory effect of NADH, or as
allosteric effector. Addition of ADP favored substrate metabolization to CO2 and
did not enhance the production of other metabolites. The controlling effect of
ADP was more pronounced when we supplied metabolites to the first part of the TCA
cycle: pyruvate, citrate, alpha-ketoglutarate and glutamine. In the second part
of the TCA cycle, the rates were primarily controlled by the concentrations of C4
dicarboxylates. Without ADP addition, the activity of the pyruvate carboxylase
malate dehydrogenase-malic enzyme cycle consumed the ATP produced by oxidative
phosphorylation, preventing its accumulation and maintaining metabolic steady
state conditions. Aspartate was taken up only in combination with pyruvate, whose
uptake also increased, a fact explained by complex regulatory effects. Isocitrate
dehydrogenase and alpha-ketoglutarate dehydrogenase were identified as the key
regulators of the TCA cycle, confirming existent knowledge from other cells. We
have shown that selectively permeabilized cells combined with elementary mode
analysis allow in-depth studying of the mitochondrial metabolism and regulation.
PMID- 26417716
TI - Characteristics of FDG-PET findings in the diagnosis of systemic juvenile
idiopathic arthritis.
AB - OBJECTIVE: To examine and delineate inflammatory focus in patients with juvenile
idiopathic arthritis (JIA), (18)F-Fluoro-deoxy-glucose (FDG)-positron emission
tomography (PET) ((18)F-FDG-PET) was applied to patients with JIA, and the images
of these patients were compared. METHODS: Sixty-eight children (59 with systemic
JIA (s-JIA) and 9 with polyarticular JIA) were included. The diagnosis of JIA was
done to meet the International League of Associations for Rheumatology (ILAR)
criteria. After 6-h fasting, whole-body positron emission tomography (PET) scans
were acquired 60 min after intravenous injection of 3-5 MBq/kg (18)F-FDG. The
interpretation of (18)F-FDG uptake was based on visual characteristics. RESULTS:
Two types of PET images were outstanding in s-JIA; one was (18)F-FDG uptake in
red bone marrow, such as the spine, pelvis, and long bones as well as spleen (12
cases), and other type was the uptake in the major joints, such as hips, elbows,
wrists, knees, and ankles (8 cases). The former findings were correlated with
elevated levels of inflammatory markers, while the latter were with significantly
increased levels of MMP-3 (p < 0.05). CONCLUSION: There was a noticeable
accumulation of (18)F-FDG uptake in bone marrow of s-JIA patients which may
indicate the inflammatory focus of this disease and play an important role in the
pathogenic basis of arthritis and systemic inflammation of s-JIA.
PMID- 26417712
TI - 123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma.
AB - BACKGROUND: Neuroblastoma is an embryonic tumour of childhood that originates in
the neural crest. It is the second most common extracranial malignant solid
tumour of childhood.Neuroblastoma cells have the unique capacity to accumulate
Iodine-123-metaiodobenzylguanidine (123I-MIBG), which can be used for imaging the
tumour. Moreover, 123I-MIBG scintigraphy is not only important for the diagnosis
of neuroblastoma, but also for staging and localization of skeletal lesions. If
these are present, MIBG follow-up scans are used to assess the patient's response
to therapy. However, the sensitivity and specificity of 123I-MIBG scintigraphy to
detect neuroblastoma varies according to the literature.Prognosis, treatment and
response to therapy of patients with neuroblastoma are currently based on
extension scoring of 123I-MIBG scans. Due to its clinical use and importance, it
is necessary to determine the exact diagnostic accuracy of 123I-MIBG
scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy
glucose ((18)F-FDG) positron emission tomography (PET) is often used and the
diagnostic accuracy of this test should also be assessed. OBJECTIVES: PRIMARY
OBJECTIVES: 1.1 To determine the diagnostic accuracy of 123I-MIBG (single photon
emission computed tomography (SPECT), with or without computed tomography (CT))
scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis
or at recurrence in children from 0 to 18 years old.1.2 To determine the
diagnostic accuracy of negative 123I-MIBG scintigraphy in combination with (18)F
FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first
diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on
test. SECONDARY OBJECTIVES: 2.1 To determine the diagnostic accuracy of (18)F-FDG
PET(-CT) imaging for detecting a neuroblastoma and its metastases at first
diagnosis or at recurrence in children from 0 to 18 years old.2.2 To compare the
diagnostic accuracy of 123I-MIBG (SPECT-CT) and (18)F-FDG-PET(-CT) imaging for
detecting a neuroblastoma and its metastases at first diagnosis or at recurrence
in children from 0 to 18 years old. This was performed within and between
included studies. 123I-MIBG (SPECT-CT) scintigraphy was the comparator test in
this case. SEARCH METHODS: We searched the databases of MEDLINE/PubMed (1945 to
11 September 2012) and EMBASE/Ovid (1980 to 11 September 2012) for potentially
relevant articles. Also we checked the reference lists of relevant articles and
review articles, scanned conference proceedings and searched for unpublished
studies by contacting researchers involved in this area. SELECTION CRITERIA: We
included studies of a cross-sectional design or cases series of proven
neuroblastoma, either retrospective or prospective, if they compared the results
of 123I-MIBG (SPECT-CT) scintigraphy or (18)F-FDG-PET(-CT) imaging, or both, with
the reference standards or with each other. Studies had to be primary diagnostic
and report on children aged between 0 to 18 years old with a neuroblastoma of any
stage at first diagnosis or at recurrence. DATA COLLECTION AND ANALYSIS: One
review author performed the initial screening of identified references. Two
review authors independently performed the study selection, extracted data and
assessed the methodological quality.We used data from two-by-two tables,
describing at least the number of patients with a true positive test and the
number of patients with a false negative test, to calculate the sensitivity, and
if possible, the specificity for each included study.If possible, we generated
forest plots showing estimates of sensitivity and specificity together with 95%
confidence intervals. MAIN RESULTS: Eleven studies met the inclusion criteria.
Ten studies reported data on patient level: the scan was positive or negative.
One study reported on all single lesions (lesion level). The sensitivity of 123I
MIBG (SPECT-CT) scintigraphy (objective 1.1), determined in 608 of 621 eligible
patients included in the 11 studies, varied from 67% to 100%. One study, that
reported on a lesion level, provided data to calculate the specificity: 68% in
115 lesions in 22 patients. The sensitivity of 123I-MIBG scintigraphy for
detecting metastases separately from the primary tumour in patients with all
neuroblastoma stages ranged from 79% to 100% in three studies and the specificity
ranged from 33% to 89% for two of these studies.One study reported on the
diagnostic accuracy of (18)F-FDG-PET(-CT) imaging (add-on test) in patients with
negative 123I-MIBG scintigraphy (objective 1.2). Two of the 24 eligible patients
with proven neuroblastoma had a negative 123I-MIBG scan and a positive (18)F-FDG
PET(-CT) scan.The sensitivity of (18)F-FDG-PET(-CT) imaging as a single
diagnostic test (objective 2.1) and compared to 123I-MIBG (SPECT-CT) (objective
2.2) was only reported in one study. The sensitivity of (18)F-FDG-PET(-CT)
imaging was 100% versus 92% of 123I-MIBG (SPECT-CT) scintigraphy. We could not
calculate the specificity for both modalities. AUTHORS' CONCLUSIONS: The reported
sensitivities of 123-I MIBG scintigraphy for the detection of neuroblastoma and
its metastases ranged from 67 to 100% in patients with histologically proven
neuroblastoma.Only one study in this review reported on false positive findings.
It is important to keep in mind that false positive findings can occur. For
example, physiological uptake should be ruled out, by using SPECT-CT scans,
although more research is needed before definitive conclusions can be made.As
described both in the literature and in this review, in about 10% of the patients
with histologically proven neuroblastoma the tumour does not accumulate 123I-MIBG
(false negative results). For these patients, it is advisable to perform an
additional test for staging and assess response to therapy. Additional tests
might for example be (18)F-FDG-PET(-CT), but to be certain of its clinical value,
more evidence is needed.The diagnostic accuracy of (18)F-FDG-PET(-CT) imaging in
case of a negative 123I-MIBG scintigraphy could not be calculated, because only
very limited data were available. Also the detection of the diagnostic accuracy
of index test (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma tumour and
its metastases, and to compare this to comparator test 123I-MIBG (SPECT-CT)
scintigraphy, could not be calculated because of the limited available data at
time of this search.At the start of this project, we did not expect to find only
very limited data on specificity. We now consider it would have been more
appropriate to use the term "the sensitivity to assess the presence of
neuroblastoma" instead of "diagnostic accuracy" for the objectives.
PMID- 26417718
TI - Two bent-shaped pi-organogelators: synthesis, fluorescence, self-assembly and
detection of volatile acid vapours in gel films and in gel-gel states.
AB - Two novel bent-shaped pi-organogelators 6a and 6b having different terminal
pyridine rings as responsive sites were designed, synthesized and fully
characterized. A subtle difference in the position of the N atom at the pyridine
ring greatly affected their fluorescence and gelation properties. 6b showed
remarkably stronger fluorescence both in solution and in the solid state as
compared to 6a. Theoretical calculation revealed a clear discrepancy in the
electron distribution between them. Furthermore, driven by pi-pi stacking
interaction and hydrophobic interaction, both 6a and 6b can gelate several
organic solvents with different polarities. Rheological studies, spectroscopic
tests and powder X-ray diffraction showed that 6a displayed a closer stacking
mode leading to stronger gel robustness. The xerogel films of 6a and 6b were
prepared and utilized to detect acid vapours. Both of them can fulfil the
detection of acid vapours through a distinct fluorescence change which could be
seen by the naked eye under a UV lamp, but with different sensing modes. A rare
gel to gel transformation was also observed upon exposure to acid vapours
accompanied by a morphological change.
PMID- 26417719
TI - Unique prototropy of meso-alkylidenyl carbaporphyrinoid possessing one meso
exocyclic double bond.
AB - Generic synthesis, identification of structural identity, unique prototropy and
spectroscopic properties of meso-alkylidenyl-thia(m-benzi)porphyrinoid containing
one exocyclic double bond at the meso-position were presented.
PMID- 26417717
TI - Multigenerational epigenetic inheritance in humans: DNA methylation changes
associated with maternal exposure to lead can be transmitted to the
grandchildren.
AB - We report that the DNA methylation profile of a child's neonatal whole blood can
be significantly influenced by his or her mother's neonatal blood lead levels
(BLL). We recruited 35 mother-infant pairs in Detroit and measured the whole
blood lead (Pb) levels and DNA methylation levels at over 450,000 loci from
current blood and neonatal blood from both the mother and the child. We found
that mothers with high neonatal BLL correlate with altered DNA methylation at 564
loci in their children's neonatal blood. Our results suggest that Pb exposure
during pregnancy affects the DNA methylation status of the fetal germ cells,
which leads to altered DNA methylation in grandchildren's neonatal dried blood
spots. This is the first demonstration that an environmental exposure in pregnant
mothers can have an epigenetic effect on the DNA methylation pattern in the
grandchildren.
PMID- 26417720
TI - Physical Therapist-Delivered Pain Coping Skills Training and Exercise for Knee
Osteoarthritis: Randomized Controlled Trial.
AB - OBJECTIVE: To investigate whether a 12-week physical therapist-delivered combined
pain coping skills training (PCST) and exercise (PCST/exercise) is more
efficacious and cost effective than either treatment alone for knee
osteoarthritis (OA). METHODS: This was an assessor-blinded, 3-arm randomized
controlled trial in 222 people (73 PCST/exercise, 75 exercise, and 74 PCST) ages
>=50 years with knee OA. All participants received 10 treatments over 12 weeks
plus a home program. PCST covered pain education and training in cognitive and
behavioral pain coping skills, exercise comprised strengthening exercises, and
PCST/exercise integrated both. Primary outcomes were self-reported average knee
pain (visual analog scale, range 0-100 mm) and physical function (Western Ontario
and McMaster Universities Osteoarthritis Index, range 0-68) at week 12. Secondary
outcomes included other pain measures, global change, physical performance,
psychological health, physical activity, quality of life, and cost effectiveness.
Analyses were by intent-to-treat methodology with multiple imputation for missing
data. RESULTS: A total of 201 participants (91%), 181 participants (82%), and 186
participants (84%) completed week 12, 32, and 52 measurements, respectively. At
week 12, there were no significant between-group differences for reductions in
pain comparing PCST/exercise versus exercise (mean difference 5.8 mm [95%
confidence interval (95% CI) -1.4, 13.0]) and PCST/exercise versus PCST (6.7 mm
[95% CI -0.6, 14.1]). Significantly greater improvements in function were found
for PCST/exercise versus exercise (3.7 units [95% CI 0.4, 7.0]) and PCST/exercise
versus PCST (7.9 units [95% CI 4.7, 11.2]). These differences persisted at weeks
32 (both) and 52 (PCST). Benefits favoring PCST/exercise were seen on several
secondary outcomes. Cost effectiveness of PCST/exercise was not demonstrated.
CONCLUSION: This model of care could improve access to psychological treatment
and augment patient outcomes from exercise in knee OA, although it did not appear
to be cost effective.
PMID- 26417721
TI - Coping with patients suffering from overactive bladder: experiences of family
caregivers in Hong Kong.
AB - This article examines the experiences of family caregivers working with patients
affected by overactive bladder (OAB) in Hong Kong. Chronic diseases create
physical and emotional burdens not only for patients but also for family
caregivers, who often experience physical and emotional burnout and social
impairment. Extensive literature has pertained to caregiver experiences in
western and non-western settings; however, few studies have addressed the
livelihoods and experiences of family caregivers of patients with OAB in ethnic
Chinese communities. Because of the increasing prevalence of OAB worldwide, this
study investigated the experiences of such caregivers in Hong Kong, examining
their emotional and social needs. A qualitative research design with individual
semistructured interviews was adopted, and snowball sampling was used to recruit
35 family caregivers who were referred by patients with OAB. The participants
were interviewed individually from May to August 2013. A phenomenological
approach was adopted in the data analysis. The data revealed that all
participants had unpleasant experiences in caring for family members with OAB. A
sense of powerlessness, helplessness, confusion and guilt, as well as grievances
and social withdrawal, was prevalent, causing great physical and emotional
suffering and subsequent physical and emotional burnout. These negative
experiences were often caused by confusion regarding caretaking duties. The
negative emotions of the participants and their family members also caused a lack
of communication and mutual understanding about the disease, causing care-giving
to be even more confusing and difficult. Furthermore, because of traditional
Chinese cultural values and gender expectations, male participants experienced
the triple burden of employment, domestic duties and care-giving. More holistic
social and healthcare support services should be provided for care-giving family
members of patients with OAB patients, empowering such caregivers to attend to
family members and care for their own emotional well-being.
PMID- 26417722
TI - Evaluation of glottic view through Air-Q Intubating Laryngeal Airway in the
supine and lateral position and assessing it as a conduit for blind endotracheal
intubation in children in the supine position.
AB - INTRODUCTION: We assessed the feasibility of blind orotracheal intubation in
children using the Air-QILA as a conduit in supine position and the glottic view
grading by fiberoptic bronchoscope (FOB) through it both in supine and lateral
positions. METHODS: After ethical approval and consent, 60 children were enrolled
in the study. In the operating room, after attaching standard monitors to all
children, anesthesia was induced with sevoflurane (2-8%) in oxygen (100%). Once
the children became sedated, an i.v. access was established and injection
glycopyrrolate (10 MUg . kg(-1)), fentanyl (2 MUg . kg(-1)), and atracurium (0.5
mg . kg(-1)) were administered. After 3 min, the Air-QILA was placed in supine
position and glottic view was assessed by using FOB, in supine and right lateral
decubitus position. In all children, gradings of glottic view in two different
positions were noted. After that all children were turned supine, and orotracheal
intubation was done blindly through the Air-QILA. The success rate, insertion
time of the Air-QILA, and endotracheal intubation were noted. RESULTS: The Air
QILA placement was successful in 57 children in first attempt and three children
required second attempt. However, blind endotracheal intubations through the Air
QILA were successful in 38 children in first attempt and 12 children required
second attempt. In the remaining 10 children, where blind endotracheal intubation
through the Air-QILA remained unsuccessful, conventional laryngoscopy was
performed. In supine and lateral positions, Grade 1 glottic view was seen in 41
and 38 of total 60 patients, respectively. Turning of all children from supine to
lateral decubitus position resulted in the deterioration of grading of glottic
view in eight children and improvement in two children (P = 0.001). CONCLUSION:
The Air-QILA is an easy to place supraglottic airway device with excellent airway
seal and low airway morbidity. It may be useful as a conduit for blind
orotracheal intubation in supine position and can be used as an effective
alternative to FOB in low resource settings.
PMID- 26417723
TI - Brain extracellular matrix retains connectivity in neuronal networks.
AB - The formation and maintenance of connectivity are critically important for the
processing and storage of information in neuronal networks. The brain
extracellular matrix (ECM) appears during postnatal development and surrounds
most neurons in the adult mammalian brain. Importantly, the removal of the ECM
was shown to improve plasticity and post-traumatic recovery in the CNS, but
little is known about the mechanisms. Here, we investigated the role of the ECM
in the regulation of the network activity in dissociated hippocampal cultures
grown on microelectrode arrays (MEAs). We found that enzymatic removal of the ECM
in mature cultures led to transient enhancement of neuronal activity, but
prevented disinhibition-induced hyperexcitability that was evident in age-matched
control cultures with intact ECM. Furthermore, the ECM degradation followed by
disinhibition strongly affected the network interaction so that it strongly
resembled the juvenile pattern seen in naive developing cultures. Taken together,
our results demonstrate that the ECM plays an important role in retention of
existing connectivity in mature neuronal networks that can be exerted through
synaptic confinement of glutamate. On the other hand, removal of the ECM can play
a permissive role in modification of connectivity and adaptive exploration of
novel network architecture.
PMID- 26417725
TI - Novel method to leukoreduce murine blood for transfusion: how to reduce animal
usage.
AB - BACKGROUND: Basic research on the pathomechanisms of transfusion-related adverse
events depends on murine transfusion models, in which leukoreduction (LR) is a
prevalent standard. The commonly used neonatal LR filter (LRF) is associated with
considerable animal numbers. A more efficient method would help support the
guiding principles of "replacement, reduction, refinement" (3Rs). STUDY DESIGN
AND METHODS: Blood from C57BL/6 and C57BL/6-Tg(UBC-GFP)30Scha/J mice was
leukoreduced using (1) a neonatal LRF, (2) a syringe LRF, or (3) CD45 microbeads.
Product quality was assessed according to US Food and Drug Administration (FDA)
standards. White blood cell numbers were analyzed by flow cytometry; hemoglobin
concentrations and hematocrit were measured and in vivo posttransfusion
recoveries were determined after 2 weeks of storage. RESULTS: Using the neonatal
filter, a LR of 99.56% was achieved with wastage of 12.4 mL in comparison to
99.68% and 1-mL hold-up volume with the syringe filter and 99.11 +/- 0.24% LR and
0.1-mL wastage using microbeads. All techniques achieved FDA quality standards,
apart from posttransfusion recovery rate, which was only reached by the
microbeads-based technique. CONCLUSION: LR with CD45 microbeads not only reduces
animal usage but also provides a more efficacious method regarding
posttransfusion red blood cell recovery and, hence, provides a promising
alternative to commonly used methods.
PMID- 26417724
TI - Melanin production through novel processing of proopiomelanocortin in the
extracellular compartment of the auricular skin of C57BL/6 mice after UV
irradiation.
AB - The production of melanin is regulated by alpha-melanocyte-stimulating hormone
(alpha-MSH), which is produced from proopiomelanocortin (POMC). Keratinocytes
release POMC along with lower levels of alpha-MSH and ACTH. To clarify the
mechanism of melanogenesis after ultraviolet (UV)-irradiation, this study focused
on the expression of POMC and POMC-derived peptides after UV-irradiation. Western
blot analysis and immunoassays indicated that both POMC and alpha-MSH-like
immunoreactivity (alpha-MSH-LI) increased after UV-irradiation. However, other
POMC-derived products were very low. In hypophysectomized mice, alpha-MSH-LI
increased to the same level as in control mice after UV-irradiation. Structural
analysis revealed that the major alpha-MSH-LI product was ACTH(1-8). Furthermore,
ACTH(1-8) competed with [(125)I]-alpha-MSH for receptor binding and increased
melanin production via a melanocortin-1 receptor. These results suggested that
melanin was produced through ACTH(1-8) after UV-irradiation. Trypsin-like
enzymatic activity, which is responsible for POMC activation, increased after UV
irradiation and was identified as tryptase. In mast cell-deficient mice, which do
not produce tryptase, alpha-MSH-LI levels were unchanged after UV-irradiation.
The present study demonstrates the production of ACTH(1-8) from POMC by tryptase,
which is a novel peptide-processing mechanism in the extracellular compartment of
the skin.
PMID- 26417726
TI - SUN4 is essential for nuclear remodeling during mammalian spermiogenesis.
AB - One of the more dramatic examples of cellular reorganization occurs during
spermiogenesis in which a roughly spherical spermatid is transformed into a
mature sperm cell. A highlight of this process involves nuclear remodeling
whereby the round spermatid nucleus is sculpted into an elongated and polar
structure. This transformation in nuclear architecture features chromatin
condensation, changes in the composition and organization of the nuclear lamina
and redistribution and elimination of nuclear pore complexes. The manchette, a
cytoplasmic microtubule-based structure is thought to play a crucial role in the
remodeling process. Here we show that SUN4, a spermatid nuclear membrane protein
has an essential function in coupling the manchette to the nuclear periphery. In
the absence of SUN4, manchette microtubules appear highly disorganized and the
nucleus itself fails to elongate. Consequently, mice deficient in SUN4 display
globozoospermia with associated infertility.
PMID- 26417728
TI - Probing hydrogen bonding orbitals: resonant inelastic soft X-ray scattering of
aqueous NH3.
AB - To probe the influence of hydrogen bonding on the electronic structure of
ammonia, gas phase and aqueous NH3 have been investigated using soft X-ray
absorption (XAS), resonant inelastic soft X-ray scattering (RIXS), and electronic
structure calculations including dynamical effects. Strong spectral differences
in the XAS scans as well as in the RIXS spectra between gas phase and aqueous NH3
are attributed to orbital mixing with the water orbitals, dipole-dipole
interactions, differences in vibronic coupling, and nuclear dynamics on the time
scale of the RIXS process. All of these effects are consequences of hydrogen
bonding and the impact of the associated orbitals, demonstrating the power of XAS
and RIXS as unique tools to study hydrogen bonding in liquids.
PMID- 26417729
TI - Novel retinopathy in related Gordon setters: a clinical, behavioral,
electrophysiological, and genetic investigation.
AB - PURPOSE: To conduct ophthalmic, behavioral, electrophysiological, and genetic
testing on two related Gordon setters presented for day blindness and compare
findings with those of nine related and unrelated Gordon setters. METHODS: All
dogs underwent comprehensive ophthalmic examination. Maze testing was conducted
under different light intensities. Rod and cone function was assessed
electroretinographically. DNA samples were screened for five canine retinal
disease gene mutations. RESULTS: Ophthalmic examination was unremarkable in all
dogs. There was no notable difference between day blind dogs and the reference
population in scotopic and mesopic maze tests. Day blind dogs performed worse in
the photopic maze with slower course completion time and more obstacle
collisions. Electroretinography revealed extinguished cone function in day blind
dogs and depressed rod responses in all but two reference dogs. One reference
population dog presented with day blindness 1 year after initial examination.
Mutations that cause achromatopsia (in CNGB3) and cone-rod dystrophies (in ADAM9
and IQCB1) were not detected in any dog tested, although five reference dogs were
carriers of the mutation in C2orf71 that causes rod-cone degeneration 4 (rcd4) in
Gordon setters and in polski owczarek nizinny dogs. CONCLUSIONS: This report
describes a novel retinopathy in related Gordon setters that has clinical signs
and vision testing results consistent with achromatopsia but electroretinographic
results suggestive of cone-rod dystrophy. The majority of Gordon setters in this
study had low rod responses on electroretinography but it is unclear whether this
was indicative of rod dysfunction or normal for the breed. Longer-term
observation of affected individuals is warranted.
PMID- 26417731
TI - Classification in psychiatry: from a symptom based to a cause based model?
AB - The assumption that eventually the classification in the American Psychiatric
Association's Diagnostic and Statistical Manual of Mental Disorders (DSM) will
incorporate aspects of causation uncovered by research in neuroscience is
examined in view of the National Institute of Mental Health's NIMH Research
Domain Criteria (RDoC) project. I argue that significant advantages of
maintaining the classification system, focussed on grouped descriptions of
symptoms, are often undervalued or not considered. In this paper I will challenge
the standard view that the transition from the purely symptom based approach is
an inevitable and desirable change.
PMID- 26417730
TI - Work-related factors, job satisfaction and intent to leave the current job among
United States nurses.
AB - AIMS AND OBJECTIVES: To examine the relationships of work-related factors (e.g.,
autonomy, work schedule, supervisory and peer support) to nurses' job
satisfaction and intent to leave their current position. BACKGROUND: Low job
satisfaction and high turnover of nurses are major problems for health care. To
improve nurse retention, work-related factors associated with job satisfaction
and intent to leave should be investigated. DESIGN: A cross-sectional secondary
data analysis. METHODS: Data were obtained in 2004 from Wave 3 of the Nurses'
Worklife and Health Study. A random sample of 5000 actively licenced nurses in
Illinois and North Carolina (two U.S. states) were sent the survey in wave 1, of
which 1641 actively working bedside nurses participated in wave 3. We examined
associations of various work-related factors with job satisfaction and intent to
leave the current position. RESULTS: Nurses who were dissatisfied with their job
reported significantly higher psychological demands and lower autonomy than
nurses who were satisfied. Nurses were significantly less satisfied with their
jobs when they worked longer hours with inadequate breaks or sick days. Lack of
support from peers and supervisors was also related to significantly lower odds
of job satisfaction. For intention to leave, nurses who said they planned to
leave their current job reported significantly lower autonomy and less support
from their peers than nurses who intended to stay. CONCLUSION: A variety of
modifiable work-related factors were significantly related to job satisfaction
and intention to leave the current job among nurses. Future research should focus
on developing interventions that could mitigate these factors (e.g., by improving
work schedules, increasing autonomy and/or nurse support). The impact of such
interventions on job satisfaction and intention to leave the current position
could then be evaluated. RELEVANCE TO CLINICAL PRACTICE: To increase nurse
retention, improved schedules, autonomy and supportive work environments should
be promoted.
PMID- 26417727
TI - Groucho restricts rhomboid expression and couples EGFR activation with R8
selection during Drosophila photoreceptor differentiation.
AB - Notch and EGFR signaling pathways play important roles in photoreceptor
differentiation during Drosophila eye development. Notch signaling induces
Enhancer of Split (E(spl)) proteins to repress atonal (ato) expression and
restrict R8 photoreceptor cell fate. The R8 precursors express rhomboid (rho),
which is required for the release of active EGFR ligand to activate EGFR
signaling in surrounding cells for the subsequent stepwise recruitment. However,
it is not clear about the mechanisms of transcriptional regulation of rho and how
the lateral inhibition of Notch signaling and rho expression are coordinated. In
this study, we show that inactivation of Groucho (Gro), an evolutionally
conserved transcriptional corepressor, inhibits Ato upregulation, delays R8
determination, and promotes differentiation of R2-5 type of neurons. We
demonstrate that these phenotypes are caused by a combination of the loss of
Notch-mediated lateral inhibition and the precocious activation of EGFR signaling
due to deregulated rho expression. Blocking EGFR signaling by Pnt-RNAi in
conjunction with Gro-inactivation leads to lateral inhibition defects with
deregulated Ato expression and R8 differentiation. We further show that
inactivation of E(spl), which are the Gro binding transcription factors, causes
deregulated rho expression and extra R8 cells within and posterior to the
morphogenetic furrow (MF), and that E(spl) mediates the binding of Gro to the
regulatory regions of both rho and ato genes in eye disc cells. Our results
suggest that Gro inhibits rho expression in undifferentiated cells and represses
the expression of both ato and rho in non-R8 precursors during initiation of
photoreceptor differentiation in an E(spl)-dependent manner. The latter function
of Gro provides novel insights into the mechanism that coordinates R8
specification with the restriction of initial rho expression to developing R8
cells.
PMID- 26417732
TI - Words that heal.
AB - The value of words in the healing process runs constant to the path of
therapeutic treatment, the net of exchanges and relationships between brain
chemistry and the right words in order to heal is subtle and intricate.
Psychotherapy, a treatment with words, is shown to be a treatment that directly
affects the brain and that is able to change it stably, even in its anatomical
structure and function. According to Kandel (1999), a leading living scientist
and Nobel Prize winner for medicine and physiology, American neurologist and
psychiatrist, psychotherapy is a real cure, a biological treatment, as it
produces behavioral changes through new words and new experiences. The article
offers a brief overview of the use of the fantasy of argument, since the time of
the classical rethoric of the sophists up to the new rethoric, to illustrate how
the structure of the speech, and the dialectic ability of opposing different
thoughts, closely resembles the way of thinking. Consequently the choice of words
can be considered an instrument of great impact that is inserted in the stream of
thoughts that determines the attitude of a person, and therefore, his/her
actions. This happens whenever you communicate voluntarily, and not simply when
interacting. The right choice of words remains a turning point in all of our
relationships, not only in therapeutic situations, but in every other social
relationship in life, family or friends.
PMID- 26417733
TI - Person-centred psychopharmacotherapy: what is it? Each patient is a unique,
responsive and responsible subject.
AB - Modern psychopharmacotherapy is currently in contention both outside and within
the field of psychiatry. Conventional psychopharmacology paradigms focusing just
on a disease perspective, biological narrative and a "one fits all" treatment are
often regarded as inadequate and disjunctive. A significant proportion of
psychiatric patients achieve no improvement or only partial improvement in their
symptoms, while many of them suffer adverse and even toxic effects of
medications. Psychopharmacotherapy as a sole form of treatment may carry the
wrong message that patients don't have to change their life style and don't have
to learn any new skills, they just have to receive their medication on time
because the only problem is in brain chemistry. Evidence-based
psychopharmacotherapy and person-centered narrative psychopharmacotherapy are not
competitors but a complementuary duality, as intimately connected as brain and
soul. Narrative preserves individuality, distinctivenesss and therapeutic
context, whereas quantitative methods and evidence-based guidelines offer a solid
foundation for what is reliably and generally correct. The purpose of person
centered psychopharmacotherapy is to empower the patients to control their
disease, to re-author their problematic life story, to obtain full personal
recovery and to regain control over their life.
PMID- 26417734
TI - The Doctor Patient Relationship; what if Communication Skills are not used? A
Maltese Story.
AB - The doctor patient relationship is fundamental to the practice of medicine. In
the UK, much work has been carried out to develop taining in communication skills
for both doctors and medical students. Whereas it is true that controled trials
of communication skills are now beginning to emerge in the primary care
literature, it is also true that there is need for studies of communication
skills on the hospital ward. One alternative form of evidence for the need of
communication skills is that of anthropological studies of hospital wards. We
here summarise the observations made in one such anthropological study which was
carried out in a renal unit in Malta. The conclusion of these observations is
that the inability of the doctors to utilise communication skills is that
patients develop meaningful relationships with other groups of professionals, to
the extent that they consider them as part of an extended family. Doctors remain
isolated from all these relationships and only relate to patients from a position
of power.
PMID- 26417735
TI - The Concept of Body Language in the Medical Consultation.
AB - In this paper we wish to argue that the human body is an instrument of
communication that can be used by the individual. This can be shown by the use of
phenomenology, as described by Husserl, and that indeed empathy, as described by
phenomenology, can be seen as a link enabling two human bodies/persons to
communicate. We then wish to show from neuroscience that empathy can itself be
seen as a bodily function. We then will describe how the doctor-patient
relationship in the consultation is an extremely important type of communication
between two persons, and how teaching of consultation skills has developed. We
will show that, once consultation skills teaching was established, then study of
body language became an essential part of this teaching, as soon as the
technology was developed, and finally we will demonstrate that it is now possible
to confirm by observational and controlled trials that appropriate use of body
language does indeed enhance the effectiveness of the consultation, including, we
would suggest, by appropriate communication of empathy and understanding.
PMID- 26417736
TI - Empathy among physicians, medical students and candidates.
AB - BACKGROUND: Empathy is one of the crucial personality traits for all medical
professionals, including physicians. The importance of empathy in doctor-patient
relationship cannot be overestimated, as it is beneficial for both sides.
Regrettably, there is evidence for the decline in this trait over the course of
medical studies. SUBJECTS AND METHODS: The participants were 509 voluntary
respondents: medical school candidates (16.1%), medical students (65%), medical
trainees (9.8%), residents (6.3%) and specialists (2.8%). The Interpersonal
Reactivity Index (IRI) was administered to them, which is a self-report tool
measuring empathy. RESULTS: Gender difference in the IRI score was especially
prominent - the mean score for female respondents was 59.83 points, while in men
it was 51.16 point (p<0.001). The level of empathy did not differ significantly
in the sub-groups divided with regards to the stage of their medical career.
However, the total IRI score in women was the highest in the group of doctors,
while in post-graduated males it was the lowest. Age of the respondents
correlated positively with the perspective taking sub-scale and negatively with
the fantasy and personal distress sub-scales. CONCLUSIONS: Empathy is a trait
that is rarely being enhanced in medical students during their education. While
empathy is crucial for the development of a satisfactory doctor-patient
relationship, there is an urgent need to adopt educational programs aimed at
reinforcing empathy in medical students.
PMID- 26417737
TI - Islam, mental health and being a Muslim in the West.
AB - The allegation that, 'Being Muslim means that you cannot be British' is often
made. In view of this, we conducted a small survey (n=75) utilising purposive
sampling on Muslims residing in the United Kingdom. Participants were recruited
in a King's College London Islamic Society event in November 2014 in Guy's
Hospital, London. 75/75 (100%) of the participants recruited responded. 69/75
(94%) of respondents either disagreed or strongly disagreed that, 'Being Muslim
means that you cannot be British' (75/75 (100%) Muslim participants, 43/75
(57.3%) female participants, 32/75 (42.7%) male participants, mean Age 20.5
years, (Std. Dev. +/-2.5)). This paper broadly seeks to answer two related
questions. Firstly, 'What is the relationship between Islam and the West?' and
secondly, 'What is the relationship between Islam and mental health?' In relation
to the former, the rise of radicalization over recent years and the Islamophobia
that has ensued have brought Islam and Muslims under intense scrutiny. Hence we
feel it is both timely and important to offer a brief background of Islam and its
relevance to the Western world. In relation to the latter, for many people
religion and mental health are deeply and intimately intertwined. For example,
religion can enable a person to develop mental health resilience and Islam has
been reported to be a protective factor against suicidal behaviour. We conclude
our paper by illustrating how the two questions are interrelated. We do so by
offering an autobiographical narrative from a Muslim healthcare professional
residing in the UK who developed a mental health problem precipitated by war in
the country of his origin. His narrative includes descriptions of the role Islam
that played in his recovery as well as his attempts to reconcile seemingly
disparate aspects of his identity.
PMID- 26417738
TI - Traumatic events in childhood and their association with psychiatric illness in
the adult.
AB - INTRODUCTION: Child maltreatment is a well-known condition that is currently
considered to be associated with the development of severe psychiatric
conditions. Consequently, the authors decided to review the current literature in
order to give a complete scenario of the situation in the world and to give
recommendations about prevention and treatment as well as research goals.
METHODS: An electronic search was conducted through the means of MEDLINE database
in order to find the most up to date peer-reviewed papers, including only those
papers published in 2015. RESULTS: 15 papers were included and analyzed the
current situation in different countries: US (n.3), Australia (n.2), Ireland
(n.2), Israel (n.2), China (n.2), Indonesia (n.1), Pakistan (n.1) and Norway
(n.1). DISCUSSION: Even though sexual abuse has been studied extensively, both
physical and emotional abuse and neglect appear to be more represented within the
population of patients that had suffered from abuse. Psychiatric disorders
(mainly personality disorders, depression and anxiety), interpersonal, social and
legal outcomes are important consequences of child maltreatment. CONCLUSIONS:
Interventions and strategies are needed at different levels, from prevention to
treatment and further research is important in order to better understand the
phenomenon.
PMID- 26417739
TI - Assessing Parenting Capacity in Psychiatric Mother and Baby Units: A case report
and review of literature.
AB - AIMS AND HYPOTHESIS: This review aimed to improve infant risk assessments in the
context of maternal mental illness by identifying key predictors of poor
parenting outcomes. BACKGROUND: Inadequate parenting as a result of severe and
persistent mental illness is a common reason for courts terminating parental
rights. However, the current practice of parenting capacity assessments in the
setting of perinatal psychiatry is fraught with risks and uncertainty. A well
recognised flaw in the assessment process is the lack of valid and reliable tools
that have been specifically validated for assessing parenting capacity in mothers
with a history of mental illness and the potential risk of harm to their infant.
To date, there is only one instrument available. METHODS: A systematic search of
Medline, PsycInfo and Embase via the Ovid interface was conducted between
September and December 2014. Citation snowball sampling was also used to identify
further relevant studies. An additional search was performed in Google to access
grey literature. RESULTS: A total of 38 citations were identified, of which 8
publications focusing on the populations of England, France and Belgium met the
eligibility criteria of this review. Evidence from existing research suggests
that poor parenting outcomes in maternal psychiatric illness are strongly
associated with correlates of socio-economic inequalities. However, evidence
regarding the long-term implications of such factors is weak as only one follow
up study and no longitudinal studies were identified in this review. CONCLUSION:
Our review suggests that the use of standardised empirically validated risk
assessment tools would benefit the current practice of parenting assessments by
improving the process by which collected information is analysed. This would
enhance the accuracy of decision-making, and improve the safeguarding of the
infant. Further research is needed on medium to long-term parenting outcomes,
particularly regarding its relations to: the type of maternal psychiatric
disorder; the quality of maternal relationships; previous attachment experience;
psychiatric illness or behavioural disorder in the partner and neonatal/infant
medical complications. This would more accurately reflect the dynamic nature of
parenting and would help to determine the effectiveness of specific interventions
addressing risk factors associated with poor parenting outcomes.
PMID- 26417740
TI - A lot of mental illness starts in adolescence. Therefore should we shift some of
the spending from adult to adolescent mental health services?
AB - In May 2015 the UK elected a new government. In election campaigns, health is one
of the most important areas of debate and over the preceding 12 months, the state
of child and adolescent mental health services (CAMHS) had held a particularly
high profile in the media and in political debate. Many had suggested that the
rate of mental illness starting in adolescence is increasing and that service
provision is not of sufficient quality or scale to meet this need. A brief review
of the sources for these statistics reveals that whilst this may be true, there
is a dearth of accurate and up to date data on the scale of the need for CAMHS or
the extent to which it is being met. Nonetheless, members of all parties claimed
to support improvements in mental health service provision for children and
adolescents through increases in funding. A key question for policy makers has
therefore become, from where any additional funding might be derived. One
suggestion has been that funding be transferred from spending on adult mental
health services. The exact practical nature of such a policy is yet to be
explored in detail by government or stakeholders. The primary purpose of the
present discussion is therefore to consider the possible ethical implications of
such a policy in principle. The discussion forms part of a wider and evolving
political and professional discourse on society's and government's attitude
towards mental illness, towards the balance of individual and societal needs and
towards the balance between preventative and supportive interventions to improve
health.
PMID- 26417741
TI - Poverty and mental health: What should we know as mental health professionals?
AB - BACKGROUND: Social inequality as a social and economic phenomenon has become an
issue of common interest in Europe and other societies worldwide, mainly after
the recent global financial and economic crisis that occurred in 2008. The
increasing gap observed between socioeconomically advantaged and disadvantaged
people has caused intensive debates in politics, social sciences and in the field
of public health. Today, poverty is considered as a major variable adversely
influencing health. In this paper we will discuss the link between poverty and
mental health. SUBJECTS AND METHODS: We conducted a literature search focusing on
three main objectives: (I) to investigate the definition of "poverty"; (II) to
determine the association between poverty and major mental health problems; and
(III) to discuss the extent to which poverty could be both a cause and a
consequence of mental health. RESULTS: We identified a total of 142 relevant
papers, published between 1995 and 2014, only 32 were retained. Main findings are
summarised in this paper. CONCLUSION: Poverty can be considered as a risk factor
for mental illness. Yet the relation between poverty and mental health is
complex, without direct causation, and bidirectional. As poverty has severe
consequences not only on health but also on the whole society, combating poverty
should be placed high on the political agenda.
PMID- 26417742
TI - One of many lessons from the European Mental Health Integration Index.
AB - The Mental Health Integration Index developed by the Economist Intelligence Unit
describes and explores the challenges of European countries of integrating people
with mental illness into society and employment, within the European Union's 28
Member States, plus Norway and Switzerland. Countries have been ranked according
to estimation based on indicators of their degree of commitment to support those
living with mental illness into society and employment. The Index is based on a
list of indicators including the environment for those with mental illness, their
access to medical help and services, their opportunities--specifically job
related--and the governance of the system, including human rights issues and
efforts to combat stigma. The indicators were developed in consultation with a
panel of independent experts on mental health. Key findings of the research are
that Germany's strong healthcare system and generous social provision put it at
the top of the Index, with the UK and Scandinavian states not far behind.
However, examples of best practice "islands of excellence" in integration are not
limited to the leading countries and exists in all European Countries. The Index
reveals also the discrepancy between perfect legislation and poor implementation
of it in practice in many European countries. It proposes that the investment
figure is a proxy for seriousness in establishing good policy and practice.
According to the Index some reform plans including entire national mental health
programmes are largely aspirational and are grossly under-funded. Moreover
various levels of government responsible for the implementation of its component
parts are largely ignoring its implementation. When we consider the legislation
as an promise to professionals and people with mental health problems, this
promise is largely unfulfilled. The is a need for strong leadership in mental
health changes process, policy capacity and real financial investments in the way
of The European countries to develop community based mental health services and
system of care.
PMID- 26417743
TI - Can clinical use of Social Media improve quality of care in mental Health? A
Health Technology Assessment approach in an Italian mental health service.
AB - Clinical use of modern Information and Communication Technologies such as Social
Media (SM) can easily reach and empower groups of population at risk or affected
by chronic diseases, and promote improvement of quality of care. In the paper we
present an assessment of SM (i.e. e-mails, websites, on line social networks,
apps) in the management of mental disorders, carried out in the Mental Health
Service of Trento (Italy) according to Health Technology Assessment criteria. A
systematic review of literature was performed to evaluate technical features,
safety and effectiveness of SM. To understand usage rate and attitude towards new
social technologies of patients and professionals, we performed a context
analysis by a survey conducted over a group of 88 psychiatric patients and a
group of 35 professionals. At last, we made recommendations for decision makers
in order to promote SM for the management of mental disorders in a context of
prioritization of investments in health care.
PMID- 26417744
TI - Setting Up a Mental Health Clinic in the Heart of Rural Africa.
AB - INTRODUCTION: The World Health Organization defines health as a state of complete
physical, mental and social well-being and not merely the absence of disease or
infirmity (WHO 1948). In Africa, mental health issues often come last on the list
of priorities for policy-makers & people's attitudes towards mental illness are
strongly influenced by traditional beliefs in supernatural causes/remedies. The
massive burden attributed to mental illness in these communities, poses a huge
moral, cultural/economic challenge and requires a concerted and integrated
approach involving policy makers, mental health Practitioners, the general
public, service users and their families and other stake holders to reverse the
trend. PROJECT OBJECTIVES: Improving community awareness of mental illness.
Change the negative perception of mental illness by the community. Providing a
screening/referral pathway for mental illnesses. Providing supervision of patient
care. POTENTIAL RESULTS: Promote community participation on issues regarding
mental health with a view to challenge existing traditional attitudes and
beliefs, reduce stigma and promote health seeking behaviour.
PMID- 26417745
TI - Mental Health Support Service for University Students.
AB - SERVICE: The Mental Health Support Service provides substantial one to one
practical support for students to enable them to manage their mental health and
study to provide coordinated support and ensure compliance with the Equality Act
2010. RESOURCES: The service consists of a full time Mental Health Advisor and a
part time Support Worker and is available all year round. Supervision is received
from a Consultant Psychiatrist. ROLES: To liaise with students and professionals
when a student is admitted to hospital/Crisis Teams. Close communication with
other services such as Student Engagement, the International Office, the Chaplain
and academics. NATIONAL TRENDS: Data from the Office of National Statistics
between 2007 and 2011 have shown an increase in the number of student suicides
since the start of the recession. SURVEY FEEDBACK: Feedback highlights that
students benefit from the support and value the professional and welcoming
attitude of the team. CONCLUSION: The service continues to provide good quality
support to those who access it. Student feedback shows that they believe the
support has helped them to stay at university and complete their degree.
PMID- 26417746
TI - Could Carmelite Spirituality Promote Good Mental Health? A brief Tribute to Saint
Teresa of Avila in the 500th anniversary of her birth.
AB - Often it is overlooked that Christian Spirituality involves a personal
relationship of a human being with God. It is of interest that both the
Protestant Reformers and the exponents of the Catholic Counter Reformation agreed
upon this. Two of the greatest exponents of the Counter-Reformation, both of whom
were made Doctors of the Church because of their teaching on Prayer were Saint
Teresa of Avila and Saint John of the Cross. This year is the 500th anniversary
of the birth of Saint Teresa of Avila. Here, as a Catholic Psychiatrist, I argue
that the teaching of both saints about the prayer life, properly understood,
tends to improve self worth, and therefore must tend to help persons with mental
health problems.
PMID- 26417747
TI - Human resources and their possible forensic meanings.
AB - Forensics (forensic--before the Forum) means the application of knowledge from
different scientific fields in order to define facts in judicial and/or
administrative procedures. Nowadays forensics, besides this, finds its
application even in different economic processes. For example, forensics enters
the commercial areas of business intelligence and of different security areas.
The European Commission recognized the importance of forensics, and underscored
the importance of development of its scientific infrastructure in member States.
We are witnessing the rise of various tragedies in economic and other kinds of
processes. Undoubtedly, the world is increasingly exposed to various forms of
threats whose occurrences regularly involve people. In this paper we are
proposing the development of a new approach in the forensic assessment of the
state of human resources. We are suggesting that in the focus should be the
forensic approach in the psychological assessment of awareness of the individual
and of the critical infrastructure sector operator (CISO) in determining the
level of actual practical, rather than formal knowledge of an individual in a
particular field of expertise, or in a specific scientific field, and possible
forensic meanings.
PMID- 26417748
TI - Global strategies targeting the recruitment crisis in psychiatry: the Doctors
Academy Future Excellence International Medical Summer School.
AB - BACKGROUND: The World Health Organization has identified a chronic shortage of
psychiatrists worldwide whereas the demand for mental health services is on the
rise. Indeed mental health problems are projected to be a leading cause of
morbidity by 2020 according to the Global Burden of Disease study. Bhugra et al,
under the auspices of the Royal College of Psychiatrists and the World Psychiatry
Association, spearheaded an international study across 22 countries and
identified myriad factors that can influence career choices at pre-medical
school, medical school and postgraduate levels. The enthusiasm and passion of
mental health educators and the quality of psychiatry placements were identified
as factors that can attract medical and students and graduates to a career in
psychiatry. The Future Excellence International Medical Summer School (FEIMSS) is
a 5-day event for medical students held yearly in Manchester, UK. FEIMSS is the
largest event of its kind in the world; the 2013 cohort was comprised of 244
students from 40 countries representing 80 universities. AIMS: To improve the
image of psychiatrists and the perception of psychiatry in general with 2 brief
contact-based lectures from a consultant and an early-career psychiatrist. The
lectures incorporated references to the humanities (literature, poetry, history,
film, drama and art). METHODS: A mixed-methods study was conducted. Paper
evaluation forms were hand-distributed to participants who attended the
psychiatry talks. Items to constructs relevant to the talks were on a Likert-type
scale. Participants were given the choice of anonymity. There was space for free
text comments which were subjected to thematic analyses. RESULTS: 25/25 of the
participants responded (response rate 100%). The heterogeneous sample was
comprised of participants representing 11 countries from Japan to Kosovo. The
written feedback was exceptionally positive. For the, 'The psychiatry talks were
interesting' and, 'Attending FEIMMS improved my understanding and respect for
other cultures' constructs, 23/25 (92%) of respondents agreed or strongly agreed.
DISCUSSION: Notwithstanding the limitations of our evaluation--which to our
knowledge is the first of its kind on such an ethnically eclectic sample--our
results suggest that a brief contact-based intervention incorporating the
humanities may positively influence the perceptions of psychiatry and
psychiatrists that medical students from diverse cultural backgrounds have. We
contend that FEIMSS provides a platform to recruit medical students into
psychiatry from all over the world and enables them to develop cultural
competency.
PMID- 26417750
TI - "Dance and go on": a project of psychosocial rehabilitation on the road.
AB - The project "Dance and go on" was created with the intention of bringing out of
the Day Centre of the Department of Mental Health of Torre del Greco, the dance
group "Dance That you go" active since 2009. Dancing Bachata becomes a
rehabilitation tool to express emotions through the body and to open to the
outside, on the territory (local society), overcoming the fear of being judged by
others, the prejudice and the social stigma about mental illness. The
rehabilitation activities of the dancing group allowed patients to improve their
care of self, self-esteem, confidence in their capacities and an increase in
their social relations. The strength and cohesion of the rehabilitation group has
given to the patients the opportunity to believe in their own abilities, to
accept themselves with their difficulties and to improve the relationship with
their body in relation with each other.
PMID- 26417749
TI - Cinematherapy and film as an educational tool in undergraduate psychiatry
teaching: a case report and review of the literature.
AB - Film possesses an extraordinary power and offers an unrivalled medium for
entertainment and escapism. There are many films that revolve around a mental
illness theme and the medical specialty that most commonly features in motion
picture is psychiatry. Over the last few decades films have become increasingly
used as an educational tool in the teaching of psychiatry topics such as mental
state examination to undergraduate students. Above and beyond its utility in
pedagogy, film also has the power to heal and the term cinematherapy has been
coined to reflect this. Indeed, there are case studies of people with first-hand
experience of psychopathology who report that watching films with a mental
illness theme has contributed to their recovery. We provide a first person
narrative from an individual with schizophrenia in which he expounds on the
concepts of cinematherpy and metaphorical imagery in films which theme on
psychosis.
PMID- 26417751
TI - A holistic approach on the neurological benefits of music.
AB - A holistic perspective on human beings allows health carers to achieve an
understanding of all the physiological, psychological and social disturbances of
the patient as a whole. Through this article we wish to focus on how music has
holistic neurological benefits. Music-therapy interventions can be more
accessible and even "self-managed" by the patient's relatives. They can reinforce
social cohesion, family ties and patients' self-esteem and thus produce a better
quality of life. Overall, it is important to consider the benefits that an
evolutionary understanding of musical behaviour and a holistic clinical
perspective of the role of music may bring for rehabilitation of a wide range of
symptoms and conditions.
PMID- 26417752
TI - 'Craziness' and creativity: Psychopathology and Poetry.
AB - Not all poets have experienced psychopathology. Conversely, not all those who
have experienced psychopathology become poets. The notion, nonetheless, of there
being an association between 'craziness' and creativity, contentious though it
may be, remains a seductive one. Poetry is both beneficial for the person who is
composing or reciting it as well as the person who may be reading or listening to
it. Poetry Therapy, which falls under the remit of Art Therapy, is increasingly
being recognised as an effective form of adjunctive therapy for the treatment of
mental health problems. The main aims of this paper are to explore (and to
attempt to elucidate) if there is indeed a relationship between the artistic
temperament and mental illness and to comment on the rise and recognition of Art
Therapy.
PMID- 26417753
TI - Clinical utilisation of the "G.T. MSRS", the rating scale for mixed states: 35
cases report.
AB - The knowledge of the clinical features of the mixed states and of the symptoms of
the "mixity" of mood disorders is crucial: to mis-diagnose or mis-treat patients
with these symptoms may increase the suicide risk and make worse the evolution of
mood disorders. The rating scale "G.T. MSRS" has been designed to improve the
clinical effectiveness of both psychiatrists and GPs by enabling them to make an
early "general" diagnosis of mixed states. This study presents some cases in
which the "G.T. MSRS" scale has been used, in order to demonstrate its
usefullness.
PMID- 26417754
TI - Are there different genotypes in Bipolar II and Bipolar I disorder and if so, why
then do we tend to observe Unipolar Depression converting to Bipolar II and then
converting to Bipolar I?
AB - We review the recent literature in order to establish the importance of a
spectrum for bipolar affective disorder, and that unipolar depression, bipolar II
and bipolar I are discrete entities that may however evolve in sequence. We
discuss clinical, genetic and neurobiological data which illustrate the
differences between bipolar I and bipolar II. To fit the data we suggest a series
of multiple mood disorder genotypes, some of which evolve into other conditions
on the bipolar spectrum. Thence we discuss the nature of the bipolar spectrum and
demonstrate how this concept can be used as the basis of a staging model for
bipolar disorder.
PMID- 26417755
TI - Bipolar and Borderline Personality Disorders: a descriptive comparison of
psychopathological aspects in patients discharged from an Italian Inpatient Unit
using PANSS and BPRS.
AB - BACKGROUND: There is current scientific debate in consideration of the
possibility to consider the Borderline Personality Disorder (BPD) as a mood
disorder within the bipolar spectrum furthermore, authors reported about the
challenging differential diagnosis of BPD and Bipolar Disorder (BD). SUBJECTS AND
METHODS: 32 patients hospitalized in the Inpatient Psychiatric Unit in Perugia,
discharged with a diagnosis of BD or BPD, were included. Factor analyses of BPRS
and PANSS items were performed. Association between socio-demographic, clinical
and psychopathological variables was tested using bivariate analyses. RESULTS:
Factor analysis identified 6 Factors, explaining 67.6% of the variance,
interpreted as follow: 1) Euphoric Mania, 2) Psychosis, 3) Inhibited Depression,
4) Disorganization, 5) Psychosomatic features, and 6) Mixed features. Bivariate
analyses identified statistically significant differences between BPD and BD
according to: PANSS positive symptoms domain, BPRS total score, Euphoric Mania
and Disorganization. No statistically significant differences came up on socio
demographic and clinical aspects. CONCLUSION: Even though the sample is small,
interesting findings came out from our investigation. Our findings are in line
with the current literature. Euphoric mood, is one of the aspects which best
differentiated BD from BPD. Higher scores in Disorganization, BPRS and PANSS
positive symptoms in BD may be related to the fact that our sample is a group of
patients from an acute inpatient unit, so the impact of the symptoms severity for
BD may be remarkable.
PMID- 26417756
TI - Overlapping phenomena of bipolar disorder and epilepsy--a common pharmacological
pathway.
AB - BACKGROUND: Studies and data on prevalence, recognition and clinical features of
bipolar disorder (BD) in epilepsy remain limited. Still, there is a growing
evidence of BD and epilepsy being frequent co-morbid conditions with some
features suggesting shared pathophysiological mechanisms that include the
episodic course of both conditions, the possible kindling mechanism and the
efficacy of some antiepileptic drugs (AEDs) in BD. SUBJECTS AND METHODS: The aim
of this paper is to review concepts of overlapping phenomena of bipolar disorder
and epilepsy. A literature review of the theoretical bases of the relationship
between BD and epilepsy is presented. CONCLUSIONS: The comorbidity of epilepsy
and mood disorders was a subject of interest of many studies for decades. Bipolar
disorder and epilepsy have a number of clinical, biochemical and
pathophysiological features in common. Bipolar disorder in epilepsy, excluding
the ictal or periictal symptoms, can be categorized using standardized measures.
Standardized psychiatric interview procedures based on DSM criteria like SCID-I
or MINI provide comprehensive way to diagnose mood disorders in patients with
epilepsy.
PMID- 26417757
TI - Diffusion-weighted imaging of the brain in bipolar disorder: a case report.
AB - BACKGROUND: Some investigations strongly support a role of glial abnormalities in
the pathophysiology of bipolar disorder. The degree of white matter axonal and
myelination disruption is measured through the rate of water molecule diffusion.
High ADC measures correspond to relatively unimpeded water diffusion, while low
ADC measures reflect preserved myelinated axons. CASE REPORT: Parietal and
occipital areas may be involved in the pathophysiology of bipolar disorder,
particularly in cognition and perception, along with the prefrontal and temporal
cortices for the disruption of emotional processing. In the literature the
widespread alterations of the cortical white matter microstructure is documented.
CONCLUSIONS: This case reports demonstrates the features of the increased mean
ADC values in the left occipital lobe. Future DWI studies are expected to
investigate the correlation of white matter changes with the functional
impairment, which often persists during euthymia in bipolar disorder.
PMID- 26417758
TI - The Cambridge-Perugia Inventory for assessment of Bipolar Disorder.
AB - It is well known that Bipolar Disorder is a condition which is often under
diagnosed or misdiagnosed. We propose an inventory of questions which will help
assess the longitutinal history of the patient's illness, and to evaluate the
presence of mixed affective states, rapid cycling, and comorbidities, all of
which have an important bearing on prognosis.
PMID- 26417759
TI - Recognising Bipolar Disorders in Primary Care.
AB - Bipolar disorder, previously called 'Manic-depression', is a complex group of
conditions characterised by recurrent changes in mood and energy. Crucially, the
intensity and duration of these changes go beyond normal fluctuations and
personality traits. Bipolar Disorder is a mental health disorder, but physical
health manifestations (Smith 2013, Westman 2013, Fagiolini 2008, Young 2013) and
complications are just as important. GPs have a key role in the recognition and
management, in conjunction with secondary care colleagues. Diagnosis is often
difficult and may take several years (Smith 2011, Angst 2005, Manning 2010),
because patients usually seek help for anxiety, depression or fatigue, not
hypomania/mania, which they may not recognise. Individuals with a first episode
of mania are more likely to present directly to secondary care, sometimes via a
third party alerting the emergency services. There is also debate around the
classification, diagnosis and treatment of individuals with brief and milder mood
changes ('bipolar spectrum disorder') (Faravelli 2009, Spence 2011). In the UK,
the recent NICE Guidelines (2014) 1 only included Bipolar I and Bipolar II for
these reasons. A particular challenge for GPs is that whilst most people who have
Bipolar Disorder (and especially Bipolar II) are depressed, most people with
depression within a Primary Care setting do not have Bipolar Disorder. Thus, a
brief pragmatic screen is recommended in Primary care: ask about a family history
of Bipolar Disorder and screen for a history of mania/hypomania in individuals
with anxiety, depression or irritability, especially if there are recurrent
episodes, suicidal thoughts or a previous suicide attempt. For suspected cases,
formal diagnosis should not be made within Primary Care but individuals should be
referred for Psychiatric assessment, ideally to a Mood Disorders specialist.
PMID- 26417760
TI - The comorbidity between bipolar disorder and ADHD in a young adult: a focus on
impulsivity.
AB - Impulsivity is a complex behavioural feature of many psychiatric disorders, in
particular of risk-taking behaviour, and is an important determinant of
personality. Both ADHD and bipolar disorder express features of impulsivity. The
concept of having two or more simultaneous psychiatric conditions is an
increasingly recognised concept in the field of psychiatry, and is important
clinically for management and prognosis. Consequently, the aim of this case
presentation is to report about a young patient with both bipolar II and ADHD, in
order to better understand which of the possible clinical phenotypes of these
psychiatric conditions exist in comorbidity, mainly focusing on impulsive
features because of the relevant challenge that this psychological aspect can
represent in the clinical treatment of these patients.
PMID- 26417761
TI - The developmental stages of Bipolar Disorder: a case report.
AB - Bipolar disorder is a developing disorder; its early stages are sometimes
misdiagnosed as anxiety or depressive disorders. At the same time, these
disorders are often in comorbidity with bipolar disorder. This complex
symptomatology can lead to misinterpretation and underdiagnosis of bipolar
disorders, mainly at the earliest stages. Consequently, one of the most important
challenges for clinicians is to recognize the non specific early symptoms with
the aid of clinical information, for example a family history of bipolar
disorder. Furthermore, it is well-known that comorbid anxiety disorders can lead
to a worse prognosis in bipolar patients but it is not exactly clear to what
extent. A deeper understanding of the relationship between these comorbidities
and their stage of development will hopefully lead to better care of patients
with bipolar disorder from a younger age.
PMID- 26417762
TI - The Management of Patients with Depression In Primary Care: an Audit Review.
AB - AIMS AND METHODS: The IAPT scheme was introduced in 2007 to implement the
recommendations from NICE guidelines regarding psychological therapy for
depression. This retrospective audit carried out across two General Practice
Surgeries evaluates the care being given in relation to the standards of NICE
guidelines. RESULTS: Initial audit found variable concordance, however after
discussion of this at a local audit meeting and the displaying of posters and
leaflets detailing the IAPT scheme this was improved on re-audit. CLINICAL
IMPLICATIONS: Training should be provided to General Practitioners regarding the
standards of care for patients with low mood or depression. In this training
there should be an emphasis on the role of psychological therapy and details
given of local resources. Posters and leaflets should be clearly displayed to
allow patients to self-refer to IAPT. A close watch must be given to waiting
times for the IAPT service as demands increase.
PMID- 26417764
TI - Observing the Effects of Mindfulness-Based Meditation on Anxiety and Depression
in Chronic Pain Patients.
AB - BACKGROUND: People whose chronic pain limits their independence are especially
likely to become anxious and depressed. Mindfulness training has shown promise
for stress-related disorders. METHODS: Chronic pain patients who complained of
anxiety and depression and who scored higher than moderate in Hamilton Depression
Rating Scale (HDRS) and Hospital Anxiety and Depression Scale (HADS) as well as
moderate in Quality of Life Scale (QOLS) were observed for eight weeks, three
days a week for an hour of Mindfulness Meditation training with an hour daily
home Mindfulness Meditation practice. Pain was evaluated on study entry and
completion, and patients were given the Patients' Global Impression of Change
(PGIC) to score at the end of the training program. RESULTS: Forty-seven patients
(47) completed the Mindfulness Meditation Training program. Over the year-long
observation, patients demonstrated noticeable improvement in depression, anxiety,
pain, and global impression of change. CONCLUSION: Chronic pain patients who
suffer with anxiety and depression may benefit from incorporating Mindfulness
Meditation into their treatment plans.
PMID- 26417763
TI - Depression, family and cellular immunity: Influence of family relationships and
cellular immunity on the severity of depression.
AB - BACKGROUND: Exposure to stress activates the hypothalamic-pituitary-adrenal axis
through the release of catecholamines, which modify humoral and cellular
immunity. On the one hand, this psycho-immunological theory makes it possible to
forge links between immunity and depression. On the other hand, we know that
family determinants are an important variable in the model of vulnerability to
depression. Our study weighs the influence of cellular immunity and family
relations on the severity of depression. SUBJECTS AND METHOD: 498 inpatients with
major depressive disorder were enrolled in an open-label trial. In addition to a
socio-demographic questionnaire, they completed Olsen's FACES III and the Beck
Depression Inventory (BDI). Flow cytometry was used to assess lymphocyte subsets.
RESULTS: In terms of immunity, there are correlations between the BDI and
percentages of CD3 (p=0.015; r=-0.112), CD4 (p<0.000; r=-0.175), CD4/CD8
(p=0.045; r=-0.093) and CD16 and 56 (p=0.014; r=0.113). In terms of family
relationships, there is a correlation between the BDI and family of origin, both
for cohesion (p=0.007; r=-0.169) and adaptability (p=0.035; r=-0.133) measures.
With respect to the relationship between family dynamics and immunity, there are
correlations between adaptability in the family of origin and CD3 (p=0.04;
r=0.094) and CD4 (p=0.044; r=0.093). A logistic regression model for family
variables explained 11.4% of the BDI, compared to 12.7% for immune variables,
while a model including the two explained 16%. CONCLUSIONS: While both the family
and immunity can explain the BDI, it is surprising they have a greater effect in
combination than individually. This suggests that the psycho-immunological theory
should look at the relation between immunity and family life, notably in relation
to the family of origin.
PMID- 26417765
TI - Socio-economic cultural transformations and Depression in elderly people.
AB - The socio-economic and cultural evolution in the last decades encouraged a
significant process of transformation of the life conditions in advanced
societies, particularly the average duration of the life of the elderly
population, which since the second half of the past century has increased by
about 60%, becoming from an average of fifty years to about eighty two for women
and eighty for men. This phenomenon enables scholars and in particular demography
scholars, to assume that in 2030 the number of elderly persons will reach about
two billion worldwide. This development of an increasingly longer life
expectancy, justifies the trust in the great progress that characterizes our
society. The rapid growth of this segment of population, due to the improved
living conditions and the related progress in science, technology and medicine,
in addition to its positive aspects, also includes negative elements, which
already affect the Welfare State and, more generally, the public administration
that is called to fill the gaps that the transformation of the family and kinship
networks have treated with indifference. The problems of the increasingly long
lived, is not freed from new elements of negativity related to the physical and
mental decline that leads to the development of new diseases in addition to those
already present, ans is increasingly motivated to seek the best remedies to
shorten or eliminate the diseases of the elderly. In this context, Depression
assumes a central dimension which will surely be a central concern for the
economic, social and health impact and for the multitude of changes that put in
crisis many of the traditional institutions. This work aims to analyze through a
careful review of the scientific literature, the causes of the spread of this
disease, the diagnostic difficulties and possible solutions for prevention and
care.
PMID- 26417766
TI - Evaluation of the level of depression among medical students from Poland,
Portugal and Germany.
AB - BACKGROUND: Depression is a serious illness affecting health, family and
professional life of many people of all sectors of society. It also concerns
students, regardless of their geographical location. The Beck Depression
Inventory (BDI) is a proper tool to brief check of the level of depression
because it has high correlation with depression. The aim of this study was to
assess and compare the level of depression among medical students from Poland,
Portugal and Germany. SUBJECTS AND METHODS: Students from different countries
were asked to fill in an electronic form containing the BDI. The form was created
separately for each country, using official translation of the BDI, approved by
the competent psychiatric association. Google Drive software was used for the
electronic form, and Stat soft Statistica v10 software for statistical analysis.
RESULTS: There were statistically significant differences (p<0.05) in terms of
average score of the BDI and of the proportion of the scores more than 10 points
of medical and technology students among kinds of studies and countries. The
average score of the BDI of medical students: Poland: 13.76+/-9.99 points;
Germany: 8.49+/-7.64 points; Portugal: 7.37+/-7.67 points. The average score of
the BDI of technology students: Poland: 12.42+/-9.66 points; Germany: 10.51+/
8.49 points; Portugal: 9.25+/-8.97 points. The proportion of the scores more than
10 points of medical students: Poland 56.32% (285/506) Germany 34.92% (154/441)
Portugal 26.03% (82/315). The proportion of the scores more than 10 points of
technology students: Poland 55.01% (368/669) Germany 43.82% (156/356) Portugal
37.57% (136/362). CONCLUSIONS: The highest depression score among medical and
technology students according the BDI was found in Poland. A proper monitoring of
depression is required, as well as rapid and appropriate help for those who
suffer from it.
PMID- 26417767
TI - Evaluation of the utility of Liebowitz Social Anxiety Scale and Barratt
Impulsiveness Scale in the diagnosis of social anxiety, impulsivity and
depression.
AB - BACKGROUND: Often mental disorders are serious problems concerning psychological
well-being. They require comprehensive and specialized psychiatric and
psychological help, but there are no public methods of controlling your mental
state. The aim of study was the evaluation of the utility of Liebowitz Social
Anxiety Scale and Barratt Impulsiveness Scale in the diagnosis of social anxiety,
impulsivity and depression. SUBJECTS AND METHODS: The study included 85 persons.
The study group had 34 patients treated in an open ward of the Department of
Psychiatry and Psychotherapy of Medical University of Silesia in Katowice. The
control group included 51 persons without mental disorders. Three self-rating
questionnaires were used: Beck Depression Inventory, Barratt Impulsiveness Scale
and Liebowitz Social Anxiety Scale. Statistica v10 Statsoft software was used for
statistical analysis. RESULTS: The analyzed groups had significant differences in
terms of Beck Scale (U Mann-Whitney test p=0.000001). Average score in study
group: 22.94+/-12.50; in control group: 7.15+/-6.44. Groups had significant
differences in terms of Liebowitz Scale (U test Mann-Whitney test, p=0.000164).
Average score in the study group: 60.41+/-30.30; in control group: 35.01+/-23.94.
Groups had significant differences in terms of Barratt Scale (t-student test
p=0.000601). Average in study group: 66.35+/-9,49; in control group: 59.54+/
7.87. Significant positive correlation was observed between the results of Beck
Scale and Liebowitz Scale (r=0.64465). Correlation was not observed between the
results of the Liebowitz and Barrat (r=0.12091 and Beck and Barrat (r=0.21482).
CONCLUSIONS: The intensity of the Liebowitz Social Anxiety Scale is directly
proportional to the severity of depression according to the Beck Depression
Inventory. The degree of impulsivity by Barrat Impulsiveness Scale does not
correlate with the level of depression according to Beck Depression Inventory.
The analyzed scales are relevant in the diagnosis of mental disorders.
PMID- 26417768
TI - Symptom Frequency Characteristics of the Hamilton Depression Rating Scale of
Major Depressive Disorder in Epilepsy.
AB - BACKGROUND: Depressive disorders are common among patients with epilepsy (PWE).
The aim of this study was to explore symptom frequencies of 17-item Hamilton
Depression Rating Scale (HDRS-17) and recognize the clinical characteristics of
Major Depressive Disorder in PWE. SUBJECTS AND METHODS: A sample of 40 adults
outpatients with epilepsy and depression was diagnosed using SCID-I for DSM-IV-TR
and HDRS-17. The total HDRS-17 score was analysed followed by the exploratory
analysis based on the hierarchical model. RESULTS: The frequencies of HDRS-17
items varied widely in this study. Insomnia related items and general somatic
symptoms items as well as insomnia and somatic factors exhibited constant and
higher frequency. Feeling guilty, suicide, psychomotor retardation and depressed
mood showed relatively lower frequencies. Other symptoms had variable frequencies
across the study population. CONCLUSIONS: Depressive disorders are common among
PWE. In the study group insomnia and somatic symptoms displayed highest values
which could represent atypical clinical features of mood disorders in PWE. There
is a need for more studies with a use of standardized approach to the problem.
PMID- 26417769
TI - Recognising and Treating Depression in the Elderly.
AB - INTRODUCTION: Depression is a major contributor to healthcare costs and is
projected to be the leading cause of disease burden in middle and higher income
countries by the year 2030. Depression in later life is associated with
disability, increased mortality, and poorer outcomes from physical illness. Its
prevalence remains high throughout lifetime, with almost 14% of older adults
living in the community estimated to have clinically relevant symptoms of
depression worldwide. DIAGNOSIS: Recognizing depression in the elderly is not
always easy. Medical illnesses are a common trigger for depression. TREATMENT:
Most depressed people welcome care, concern and support, but they may be
frightened and may resist help. The treatment of depression demands patience and
perseverance for the patient and physician. Sometimes several different
treatments must be tried before full recovery. Each person has individual
biological and psychological characteristics that require individualized care.
PROGNOSIS: The prognosis for recovery is equal in young and old patients,
although remission may take longer to achieve in older patients. FURTHER CARE:
Depression is a highly treatable medical condition and is not a normal part of
growing older. Therefore, it is crucial to understand and recognize the symptoms
of the illness in the primary care.
PMID- 26417770
TI - A systematic review of structural and functional MRI differences between
psychotic and nonpsychotic depression.
AB - BACKGROUND: Psychotic depression is widely accepted as a specific subtype of
unipolar major depression. Magnetic resonance imaging studies have begun to
investigate the neurobiological changes that differentiate this subtype of major
depression from non-psychotic depression. Any differences may eventually be
useful in aiding diagnosis patients for whom there is diagnostic uncertainty.
This review collates the currently available evidence. SUBJECTS AND METHODS: A
systematic search of the Medline, PubMed, Embase & Web of Science databases was
used to identify all articles comparing structural grey matter or functional
magnetic resonance imaging (MRI) differences between adults (18+) with previously
diagnosed psychotic and nonpsychotic depression in predefined regions of interest
(hippocampus, amygdala, cingulate, insula & frontal cortices). The results were
collated and organised according to brain region. RESULTS: There is a paucity of
studies addressing structural and functional changes differentiating these two
disorders and recommendations regarding use of these modalities in diagnosis
cannot be made. From the available studies decreases in frontal cortex grey
matter volumes may differentiate psychotic from non-psychotic depression whilst
further studies are required to confirm decreases in insula cortex volumes. fMRI
studies show associations between altered activity in these two regions and
cognitive impairments in patients with psychotic depression. The volumes of
putative emotional processing regions including the amygdala, hippocampus and
anterior cingulate show no difference between psychotic and nonpsychotic
depression. CONCLUSIONS: Structural and functional changes in the higher
associative regions of the frontal and insular cortices appear to differentiate
psychotic and nonpsychotic depression to a greater degree than changes in
putative emotional processing regions. The quality of the evidence both in terms
of numbers of studies available and sample sizes involved is very poor but in
regard to directing future study, understanding the neurobiology of psychotic
depression may benefit from a more detailed assessment of these two regions.
PMID- 26417771
TI - Sociodemographic and clinical features of patients with depressive disorder in
Khartoum, Sudan.
AB - BACKGROUND: It's known worldwide that depression is becoming a major health
problem and its prevalence is increasing. The main objective of this study is to
find out the prevalence of depression among patients attending a general
psychiatric clinic, and study their sociodemographic and clinical features.
METHODS: Files of patients attending a private psychiatric clinic in Khartoum in
the period June 2005-June 2010 were reviewed. Only those with a diagnosis of
depression were chosen, sociodemographic date and clinical features were
documented and results were shown below. RESULTS AND DISCUSSION: Total numbers of
patients with depression were 137 (11.4%). Females were more than males (56.2%),
the majority are between ages 41-60 (40.9%), married (65%), (14.9%) had family
history of psychiatric disorders and (52%) had a previous history of psychiatric
treatment. Depressed mood is the commonest symptom (98.5%), loss of interest
(91.9%), reduced energy (57%), guilt feelings (17.9%) and (35.8%) of our samples
expressed suicidal ideations. The commonest type of somatic symptom is
generalized aches and pain (30.7%), (18%) were psychotic. CONCLUSION: The present
study is a retrospective descriptive study, based on a private psychiatric clinic
sample. It provided a useful baseline for more comprehensive field based studies,
to try to aid planning and development of services to meet the needs of the
population.
PMID- 26417772
TI - Suffering Depression in the Christian Church--One Person's Experience.
AB - The author has suffered for several years from Anxiety and depression. Here she
describes her experiences, both of depression and of her experience as a person
suffering from depression within the Christian Church.
PMID- 26417773
TI - Management of primary negative symptoms in schizophrenia: an one-year
observational study.
AB - Negative symptoms represent a separate symptom domain, with respect to
depression, neurocognition, and social cognition and have a strong direct and
indirect impact on real-life functioning. Furthermore, negative symptoms that do
not improve following antipsychotic treatment are an important diagnostic and
therapeutic challenge. We conducted a 12-month-study open-observational study to
evaluate the efficacy of some atypical antipsychotics on negative symptoms,
according to the following recommendations of Consensus Development Conference
Attendees. In our study, we evaluated in an open-label study the efficacy of some
second-generation antipsychotics (clozapine, quetiapine, olanzapine,
aripiprazole, paliperidone) in 42 patients with schizophrenia or schizoaffective
disorder (DSM-5 criteria) with 'persistent negative symptoms'. We used different
rating scales (PANSS, CDSs, BNSS, BPRS), but mainly we focused on the new Brief
Negative Symptoms Scale (BNSS) for negative symptoms. Our total data indicate an
overall statistically significant reduction in all scales, although not
clinically relevant.
PMID- 26417774
TI - A comparative study between cognitive impairments of adults with schizophrenia
and children with psychotic spectrum disorders: a literature review.
AB - BACKGROUND: Cognitive impairments have been extensively reported for patients
suffering from schizophrenia but a lot of questions persist about these troubles.
Several domains of cognitive functions are impaired which result in daily life
difficulties. Many arguments tend to show that children suffering from psychotic
spectrum disorders present cognitive impairments also but things are not clearly
defined. The aim of this review is to compare the cognitive impairments of
children suffering from psychotic symptoms and adults suffering from
schizophrenia in order to improve the understanding of the two clinical
affections. A better understanding of the disease is necessary to improve the
health care which currently give poor results. SUBJECTS AND METHODS: Besides the
Diagnostic and Statistical Manual (DSM-5) and the French reference books, the
present research has been conducted using PubMed, Medline, PsycINFO, PsycARTICLES
and ScienceDirect. Literature about cognitive impairments of adults with
schizophrenia and children with psychotic spectrum disorders is assessed and
results are compared. RESULTS: Both children and adults suffer from cognitive
impairments: language, memories, executive and motor functions and IQ are
impaired. An important heterogeneity in the troubles has been observed and a poor
knowledge in terms of onset time, evolution, intensity, impact on everyday life
and therapeutic interest has been reported. CONCLUSION: Adults with schizophrenia
and children suffering from psychotic spectrum disorders have similar cognitive
impairments in many domains of cognition. The similarities in term of cognitive
impairments highlighted in the present work should support new studies in order
to adapt to children the current cognitive therapies which are mostly provided to
adults. As the cognitive impairments are heterogeneous, each patient should
receive a tailored neurocognitive exam which takes into account its abilities and
weaknesses.
PMID- 26417775
TI - Atypical Antipsychotics for Schizophrenia and/or Bipolar Disorder in Pregnancy:
Current Recommendations and Updates in the NICE Guidelines.
AB - BACKGROUND: The gold standard pharmacological agents used to treat schizophrenia
and bipolar disorder in adults are antipsychotics. Atypical or second-generation
antipsychotics have superseded or used as alternatives to typical first
generation antipsychotics due to better tolerability and safety profile. However
the efficacy and safety of these drugs are severely limited in pregnancy and/or
women of childbearing potential. There are very few guidelines to guide the
clinical management of schizophrenia and/or bipolar disorder in this subgroup.
AIM: We aimed to review current evidence of atypical antipsychotics used in
pregnancy where available, with considerations to its efficacy and safety to both
the mother and fetus, in conjunction with the recently updated NICE guidelines.
METHODS: The latest NICE CG192 guidelines on antenatal and postnatal mental
health, published in December 2014 was reviewed and summarized, and the BNF
approved list of atypical antipsychotics were identified. Clinically relevant
MEDLINE-linked publications were searched and selected where available using the
PubMed search engine to identify evidence for or against the use of atypical
antipsychotics in pregnancy. RESULTS AND CONCLUSIONS: NICE CG192 improved clarity
on the prediction, support and holistic management of mental illness in pregnancy
and puerperium; however there were no specific recommendations in terms of
pharmacological agents used to treat schizophrenia and/or bipolar disorder in
this subgroup. Evidence from the literature on atypical antipsychotics yielded
discordant results. Nonetheless, our report presents preliminary findings of
certain antipsychotics which appear to be effective and safe in pregnancy. Future
research would benefit from larger, prospective randomized controlled trials, and
perhaps include newer atypical antipsychotics for consideration in this subgroup.
PMID- 26417776
TI - Effects of hormones on cognition in schizophrenic male patients--preliminary
results.
AB - BACKGROUND: Schizophrenia is a prevalent neurodevelopmental disorder of an
unknown etiology and a variable phenotypic expression. In the recent years, the
impact of hormones on the course of schizophrenia has been investigated. This
study is aimed at assessing the level of correlating serum levels of hormones in
schizophrenic male patients with their cognitive functioning measured with
neuropsychological tests. SUBJECTS AND METHODS: In the index group there were 15
medicated male schizophrenic patients. In the control group there were 15 age and
education matched healthy men. All subjects underwent analysis of serum hormones
level (TSH, testosterone, estradiol, FSH, LH, progesterone and prolactin) and a
battery of tests (Trail Making Test A and B, Stroop Test, Verbal and Semantic
Fluency Test). RESULTS: The mean serum levels of the following hormones were
higher in the index group than in the control group: TSH (1.76 mIU/L vs 1.58
mIU/L; p=0.66), progesterone (0.85 ng/ml vs 0.69 ng/ml; p=0.22) and prolactin
(558.71 uIU/ml vs 181 uIU/ml; p=0.025). The mean levels of estradiol (24.36 pg/ml
vs 25.40 ng/ml; p=0.64), FSH (3.17 mIU/ml vs 5.72 mIU/ml; p=0.019), LH (3.85
mIU/ml vs 5.77 mIU/ml; p=0.056) and testosterone (2.90 ng/ml vs 5.38 ng/ml;
p=0.003) were higher in the control group. In the index group there were
significant negative correlations between FSH and semantic fluency (rho=
0.678606), progesterone and: TMT B (rho=-0.586763), Stroop 1 (rho=-0.701880) and
Stroop 2 (rho=-0.601074) and prolactin and TMT A (rho=-0.579607). CONCLUSIONS:
The preliminary results of our study show that serum levels of FSH and
testosterone are significantly lower, whereas the level of prolactin is markedly
higher, in schizophrenic male patients than in healthy men. There is an inverse
correlation between serum levels of progesterone, FSH and prolactin and the
results of certain cognitive functioning tests in schizophrenic men.
PMID- 26417777
TI - Long term telemedicine study of compliance in paranoid schizophrenia.
AB - BACKGROUND: Low compliance is one of the crucial problems of contemporary
psychiatry. Relapses, deterioration of cognitive functioning, negative symptoms,
neuroleptic resistance are the examples of many consequences of noncompliance in
schizophrenia SUBJECTS AND METHODS: The study was designed to assess the
compliance in the 200 patients diagnosed with paranoid schizophrenia, all in the
state of symptomatic remission and on the stable neuroleptic treatment. The
compliance was assessed using a telepsychiatric system, sending reminders: 1 hour
before the planned dose to remind them that drug intake is approaching, and at
the moment of intake to check if they took the drug. The confirmed drug intakes
were counted by the telepsychiatric system. RESULTS: 158 patients completed the
study period. The compliance in the first month of the treatment was 44.6% and
decreased over the rest of the period to the level of 33.4%. 50% of the
schizophrenic patients were compliant at a level lower than 37%. This group was
considered the low compliance group, and in this group the compliance increased
after 6 months from 9.3% to 10.3% (p<0.0001). CONCLUSIONS: The compliance in the
group of schizophrenic patients in remission is very low. The telemedicine system
improves the compliance in the patients with the worst compliance.
PMID- 26417778
TI - In search of neural mechanisms of mirror neuron dysfunction in schizophrenia:
resting state functional connectivity approach.
AB - It has been repeatedly shown that schizophrenia patients have immense alterations
in goal-directed behaviour, social cognition, and social interactions, cognitive
abilities that are presumably driven by the mirror neurons system (MNS). However,
the neural bases of these deficits still remain unclear. Along with the task
related fMRI and EEG research tapping into the mirror neuron system, the
characteristics of the resting state activity in the particular areas that
encompass mirror neurons might be of interest as they obviously determine the
baseline of the neuronal activity. Using resting state fMRI, we investigated
resting state functional connectivity (FC) in four predefined brain structures,
ROIs (inferior frontal gyrus, superior parietal lobule, premotor cortex and
superior temporal gyrus), known for their mirror neurons activity, in 12 patients
with first psychotic episode and 12 matched healthy individuals. As a specific
hypothesis, based on the knowledge of the anatomical inputs of thalamus to all
preselected ROIs, we have investigated the FC between thalamus and the ROIs. Of
all ROIs included, seed-to-voxel connectivity analysis revealed significantly
decreased FC only in left posterior superior temporal gyrus (STG) and the areas
in visual cortex and cerebellum in patients as compared to controls. Using ROI-to
ROI analysis (thalamus and selected ROIs), we have found an increased FC of STG
and bilateral thalamus whereas the FC of these areas was decreased in controls.
Our results suggest that: (1) schizophrenia patients exhibit FC of STG which
corresponds to the previously reported changes of superior temporal gyrus in
schizophrenia and might contribute to the disturbances of specific functions,
such as emotional processing or spatial awareness; (2) as the thalamus plays a
pivotal role in the sensory gating, providing the filtering of the redundant
stimulation, the observed hyperconnectivity between the thalami and the STGs in
patients with schizophrenia might explain the sequential overload with sensory
inputs that leads to the abnormal cognitive processing.
PMID- 26417779
TI - How does Schizophrenia occur and can delusions be protective to the person? A
bird's eye view attempting to Integrate the Neurobiology and Psychology of
Schizophrenia.
AB - This short paper is an attempt to integrate what we know about the biological
development of schizophrenia. It attempts to integrate Neurodevelomental,
Dopamine, Glutamate, Salience and Psychological theories of the development of
schizophrenia into a unitary whole, and thus to illustrate how these theories
relate together. It is a summary of a much larger work, presently in preparation,
done for the purposes of the present coference. It attempts to describe the
biological development of schizophrenia, and thence the delusions and
hallucinations which play a part in it symptomatically.
PMID- 26417780
TI - Suicide and attempted suicide: epidemiological surveillance as a crucial means of
a local suicide prevention project in Trento's Province.
AB - The World Health Organization identifies suicide among the top 10 causes of death
in many countries with an overall mortality rate of 16 per 100,000 inhabitants.
Furthermore suicide attempts present a frequency 4-10 times greater than the
suicidal events, representing also one of the main risk factors to lead to
recurrent attempts of suicide. In 2008 the Autonomous Province of Trento launched
a suicide prevention pogram called "Invitation to Life" which includes various
interventions intended to counter the phenomenon of suicide in the region.
Actually the epidemiological research upon the phenomenon of suicide in Trentino
region is one of the main pillars of the project: it represents a fundamental
requirement to identify risk and protective factors in the population in order to
adopt more specific and effective preventive strategies. This article aims to
present methods and instruments for epidemiological monitoring of suicide and
attempted suicide which are applied in Trentino and to describe results after
seven years from the beginning of the local prevention program "Invitation to
life".
PMID- 26417781
TI - Personality and psychotic symptoms as predictors of self-harm and attempted
suicide.
AB - BACKGROUND: Nonfatal suicidal behaviours (NSB), including suicide ideation,
suicide plan and suicide attempt, constitute a serious problem for public
healthcare services. Suicide gesture (SG) which refers to self-injurious
behaviour with no intent to die, differs from NSB in a variety of important ways.
The aim of this study was to investigate demographic and clinical characteristics
of NSB and SG to examine whether self-injurers with intent to die differ
significantly from self injurers without such intent. METHODS: All admissions for
NSB and SG to the Psychiatric Inpatient Unit of University / General Hospital
Santa Maria della Misericordia, Perugia, Umbria, Italy, from January 2015 to June
2015 were included in a medical record review. Basic descriptive statistics and
distributional properties of all variables were first examined. Bivariate
analyses were performed using Chi-square tests for group comparisons and t-test
for independent samples used when appropriated. RESULTS: The study sample
included 38 patients. Of these 23 had committed NSB (13.1%), 15 had commetted SG
(8.5%). Number of married NSB was significantly higher than the number of married
SG (p=0.08). We found a significant difference between NSB and SG related to the
item of impulse control that was poorer in SG than NSB (p=0.010). BPRS items of
hostility (p=0.082), suspiciousness (p=0.042) and excitement (p=0.02) were found
to be significantly higher in SG than NSB. Borderline personality disorder
(p=0.032) and Passive-Aggressive personality disorder (p=0,082) diagnosed by the
means of the SCID-II, were more represented in SG than NSB (p=0.044). Schizoid
personality disorder was significantly related to NSB (p=0.042). No others
significant differences were found. CONCLUSIONS: NSB and SG are different for
many psychopathological characteristics. These results confirm the importance of
classifying individuals on the basis of the intent to die. Additional research is
needed to understand and elucidate psychopatological and clinical characteristics
of the different categories of self-injurers to find risk factors specific to
suicide attempts.
PMID- 26417783
TI - Suicide in adolescence: attempt to cure a crisis, but also the fatal outcome of
certain pathologies.
AB - BACKGROUND: Teen suicide is an alarming public health issue. The purpose of this
paper is to better understand the reasons behind attempting/committing suicide.
Our research focuses on adolescent psychopathology and on pathologies that are
considered as adolescent suicide risk factors. SUBJECTS AND METHODS: We conducted
literature-based research. The first part of this research was based on
adolescent psychopathological traits, whilst the second concentrated on the most
frequently made diagnoses in the case of adolescents who had attempted suicide.
RESULTS: Adolescence is a period of life characterized by great instability,
where everything is called into question. We can observe a high propensity
towards taking action, which allows the adolescent to bypass certain questions
that they cannot answer. This takes place against a background where the body,
which is undergoing change, becomes the scene, the means and the purpose to
answer these questions, once and for all, through suicide. Notwithstanding, the
studies also show that, setting aside these psychopathological considerations
that characterize every adolescent, certain diagnoses are commonly related to
adolescent suicide and, as such, constitute risk factors. These pathologies are
as follows: depression, adjustment disorder and personality disorder. We can,
however, include some precisions as regards the frequency of these diagnoses,
given that adolescence is inherently a period of life characterized by depression
and that the future adult is obliged to adjust. CONCLUSIONS: Teen suicide is,
therefore, conditioned by pathological behaviour, which is part of a necessary
and normal transition, but one which is occasionally stimulated by certain
pathological instabilities.
PMID- 26417782
TI - Comparison of assessment and management of suicidal risk for acute psychiatric
assessment between two state sponsored hospitals in England and Italy.
AB - The risk of suicide is one of the most important risk factors looked into for
acute psychiatric assessments that influences the management plan. The prevalence
of suicide is on a rise across European countries; as a consequence, the
different countries have created specific guidelines and policies in order to
prevent suicides in the acute settings. These guidelines are based on both
different cultural aspects as well as the different organization of the mental
health system in the different countries. This paper wants to present the
comparison between the guidelines of two European countries, England and Italy,
in order to evaluate the systems, understand differences and common contact
points. The different European countries could learn one from the other and a
European shared point of view may be a way forward to create better understanding
and preventing the risk of suicide across the population.
PMID- 26417784
TI - Hormonal and developmental influences on adolescent suicide: a systematic review.
AB - BACKGROUND: Teen suicide is a major public health problem. In the United States,
it is the third cause of death among the 10-24 year olds. Adolescence involves
numerous changes, whether physical, social, emotional or hormonal. At a
neurobiological level, a teenager's nervous system is also affected and undergoes
significant modifications. SUBJECTS AND METHODS: We conducted a systematic review
of electronic literature published between January 1990 and August 2014 via
MEDLINE, PubMED and PsychINFO to list articles concerning the risk of teen
depression and suicide risks in adolescents as well as those relating to the
adolescent's neuro-anatomical brain and the effect that puberty has on it.
RESULTS AND DISCUSSION: When analyzing the various studies, it is clear that all
support the idea that adolescence is a special period, both at neuroanatomical
and biological levels. The risk of impulsiveness and depression is explained,
anatomically, by a faster maturation of the limbic system, and biologically, by a
higher sensitivity of the serotoninergic system and to glucocorticoids, which
themselves are influenced by the specific hormonal environment during this
period. Moreover and above all, adolescence is a vulnerable time for many
reasons: physical, hormonal, social, cognitive, and emotional changes, self
development, etc. We should not restrict it to structural neurological changes
without taking into account the other factors or compartmentalize young people
into a reductive model based on determinism. CONCLUSIONS: Adolescence is a time
of change, transformation, and adaptation. The hormonal events that occur during
this period have significant effects on brain development, neuro-cerebral
chemistry, adolescent behavior and risks of depression. It is important to try to
prevent suicide and depression in adolescents considering its entirety and
complexity but also by paying attention to neuro-biological factors even if, at
present, many research projects are currently underway to develop an appropriate
drug therapy strategy.
PMID- 26417786
TI - An economic analysis of different cannabis decriminalization scenarios.
AB - BACKGROUND: Cannabis is the most widely used illegal drug in European countries.
In countries with repressive cannabis policies, prevalence is not lower than in
those with tolerant laws. Repressive policies not only have uncertain benefits
but they are also expensive. Economists tend to believe that good public policies
minimize social costs; that is, they help to improve collective wellbeing at a
lower cost. METHOD: The paper draws on a review of international literature on
cannabis legislative models around the world. After a description of some of the
fundamental concepts of a market economy, several existing policy scenarios will
be presented and analyzed from an economic perspective. Strength and weaknesses
will be summarized for each alternative. RESULTS: In addition to consumption
tolerance in countries such as the Netherlands, recent decriminalization of
domestic markets in the Unites States and Uruguay present alternatives to reduce
the negative impact of cannabis on society. Earlier initiation age and rise in
consumption are unintended potential consequences of decriminalization that need
to be addressed by public authorities when designing a liberalized cannabis
policy environment. Price is a key variable that needs to be addressed to prevent
a rise in consumption. CONCLUSION: Repressive cannabis policies are expensive and
have limited impact on consumption. Consumption legalization significantly
reduces expenses for repression and law enforcement, allowing for the allocation
of more resources to other targets such as education and prevention. With
legalization of supply along with consumption, repression and law enforcement
costs are reduced even further. Moreover, a legal market would create employment
and generate tax revenues that could be allocated to the prevention of increased
consumption. Legalizing cannabis would not lead to a sudden rise in consumption,
providing the duty imposed by the state kept the product at its current price.
PMID- 26417785
TI - Relaxation and Impact on the Multidimensional Health Locus of Control: Interest
of group psychoeducation for stress management in the context of liaison
psychiatry within a General Hospital.
AB - BACKGROUND: In this article we propose a model for caring for a group focusing on
psychoeducation for stress management and learning relaxation designed for
patients experiencing somatization and who were recruited during organic medicine
consultations. We are developing an interest for this kind of group from a
clinical and practical point of view and have sought to demonstrate the impact
that this kind of care can have on health representations among these patients
through using the MHLC (Multidimensional Health Locus of Control) questionnaire.
SUBJECT AND METHODS: Participants in the stress management and relaxation groups
completed the questionnaire at the beginning of the first session and at the end
of the second and last session. We collected 94 usable questionnaires between
January 2008 and December 2014 and processed the data using Student's t-test on
paired samples. RESULTS: The results tend to demonstrate that psychoeducation for
stress management and relaxation reduces internality scores in patients with high
scores and the opposite for patients whose internality scores are low.
DISCUSSION: Our research protocol does not enable us to distinguish between the
respective influences of the psychoeducation group and the relaxation group.
CONCLUSION: The psychoeducation groups for stress management and relaxation have
an impact on health representations in patients experiencing somatization who
would not have spontaneously sought out psychiatric consultations.
PMID- 26417787
TI - Neuropsychiatric Manifestations of Colloid Cysts: a review of the literature.
AB - Colloid cysts account for approximately 2% of primary brain tumours and the
majority of cases are identified in the fourth and fifth decade. They are small,
gelatinous neoplasms lined by a single layer of mucin-secreting columnar
epithelium that are thought to arise from errors in folding of the primitive
neuroepithelium. They develop in the rostral aspect of the third ventricle in the
foramen of Monro in 99% of cases and despite their benign histology carry a poor
prognosis, with a mortality greater than 10% in symptomatic cases. The location
of colloid cysts within the ventricular system results in obstruction of the
foramen of Monro as the cyst grows, disrupting the circulation of cerebrospinal
fluid (CSF) and causing hydrocephalus. This is the mechanism behind the most
common presenting symptoms of postural headache, nausea and vomiting - a clinical
picture synonymous with hydrocephalus and intracranial pathology. In addition to
these classical neurological symptoms, there is a high prevalence of psychiatric
symptoms in the patient population, with symptoms ranging from anterograde
amnesia to gustatory hallucination. These symptoms can occur with or without the
presence of hydrocephalus, and are thought to be secondary to compression of
connecting pathways between the mesocortices and subcortical limbic regions.
These symptoms have been shown to be comparative in frequency to the classical
symptoms, yet are rarely the reason for referral to a neurological or
neurosurgical service for investigation.
PMID- 26417788
TI - Psychiatric caregiver stress: clinical implications of compassion fatigue.
AB - The capacity to work productively is a key component of health and emotional well
being. People who work in health care can be exposed to the fatigue of care.
Compassion fatigue has been described as an occupational hazard specific to
clinical work related severe emotional distress. In our study, we have evaluated
compassion fatigue in a mental health group (47 psychiatric staff) and its
relationship with inpatients (237 inpatients) affected by some psychiatric
disorders. At baseline, the more significant data indicate a high percentage of
Job Burnout and Compassion Fatigue in psychiatric nurses (respectively, 39.28%,
28.57%). Significant Compassion Fatigue percentage is present also in
psychologist group (36.36%). Finally, in psychiatrists, the exposure to patients
increased vicarious trauma (28.57%), but not job burnout. After a year of
participation in Balint Groups, the psychiatric staff presented an overall
reduction in total mean score in any administered scale (CBI: p<0.0000045; sCFs:
(Vicarious Trauma: p<0.0288; Job Burnout: p<0.000001)). Thus, compassion fatigue
causes concern among mental health professionals, and Balint Groups may represent
a therapeutic strategy to help health professionals to face difficulties in
challenging work environments.
PMID- 26417789
TI - A questionnaire to assess social stigma.
AB - Psychiatric patients often suffer for two reasons: due to the illness and due to
the social stigma of mental illness, that increases the uneasiness and psychic
pain of the person suffering from serious psychiatric disorder. This unwell
person is often the object of stigma because he is "different" from others, and
he also can be margenalised by society. In this study we intend to assess whether
these margenalising attitudes might be also present among mental health
professionals who have presented psychic problems in a previous period of their
life, against sick persons suffering of the same illness even if he is a mental
health professional. Two questionnaires have been developed, one for
professionals and another for the patients, with the aim of identifying these
marginalising attitudes. We intend that this study shall be a multicenter,
observational and international study, promoted by the Mental Health Dept. of
Naples (ASL Naples 3 South, Italy).
PMID- 26417790
TI - The psychosomatic spectrum: a clinical-analytic survey of the relationship
between eating disorders and migraine.
AB - OBJECTIVE: To evaluate if somatic symptoms of Eating Disorders and Migraine
reflect similar aspects of personality and temperament. METHODS: The clinical
notes of 27 migraineurs and of 26 ED outpatients were reviewed; 40 medical
students of the University of Perugia were recruited as healthy controls. TCI,
DMI, SCID-II and TAS-20 were used. STATISTICAL ANALYSIS: performed by logistic
regression, a cluster analysis that gave the weight for the three groups, and a
logistic regression of the cluster analysis. RESULTS: Patients showed medium
scores in almost all the scales of the different tests. High scores in HA and low
scores in NS characterized both migraine and ED patients. Logistic regression of
the cluster analysis underscored that ED patients, migraineurs, and controls
differed for HA (435.424, p<=0.0001), TAS-20 F2 (difficulty in describing
feelings to others; 7.087, p=0.029), and the defense mechanism turning against
object (6.702, p=0.035). DISCUSSION: The temperamental aspects of low NS and high
HA represent the core symptoms of a spectrum composed of somatizing patients who
use affective and behavioral strategies that are not functional enough in
affective regulation.
PMID- 26417791
TI - Can Violence cause Eating Disorders?
AB - The origin and course of eating disorders and nutrition have a multifactorial
etiology and should therefore take into consideration: psychological factors,
evolutionary, biological and socio-cultural (Juli 2012). Among the psychological
factors we will focus on violence (in any form) and in particular on the
consequences that they have on women, which vary in severity. Recent studies show
that women get sick more than men, both from depression and eating disorders,
with a ratio of 2:1; this difference begins in adolescence and continues
throughout the course of life (Niolu 2010). The cause of this difference remains
unclear. Many studies agree that during adolescence girls have negative feelings
more frequently and for a longer duration caused by stressful life events and
difficult circumstances, such as abuse or violence. This results in an increased
likelihood of developing a symptom that will be connected to eating disorders
and/or depression. As far as the role of food is concerned in eating disorders,
it has a symbolic significance and offers emotional comfort. Eating means to
incorporate and assimilate, and even in an ideal sense, the characteristics of
the foods become part of the individual. Feelings that lead to binges with food
are normally a result of feelings related to abuse or violence and lead to
abnormal behavior which leads to binging and the final result being that the
person is left feeling guilty and ashamed. Research confirms that 30% of patients
who have been diagnosed with eating disorders, especially bulimia, have a history
of sexual abuse during childhood. Ignoring the significance of this factor can
result in the unleashing of this disease as the patient uses the disorder as his
expressive theater (Mencarelli 2008). Factors that contribute to the possibility
of developing an eating disorder are both the age of the patient at the time of
the abuse and the duration of the abuse. The psychological effects that follow
may include dissociative symptoms and symptoms of an Eating Disorder.
PMID- 26417792
TI - Psychiatric disorders associated with Cushing's syndrome.
AB - BACKGROUND: Cushing's syndrome is the term used to describe a set of symptoms
associated with hypercortisolism, which in most cases is caused by hypophysial
microadenoma over-secreting adrenocorticotropic hormone. This endocrine disorder
is often associated with psychiatric comorbidities. The most important include
mood disorders, psychotic disorders, cognitive dysfunctions and anxiety
disorders. SUBJECT AND METHODS: The aim of this article was to review the
prevalence, symptoms and consequences of psychiatric disorders in the course of
Cushing's syndrome. We therefore performed a literature search using the
following keywords: Cushing's syndrome and psychosis, Cushing's syndrome and
mental disorders, Cushing's syndrome and depression, Cushing's syndrome and
anxiety. RESULTS: The most prevalent psychiatric comorbidity of Cushing's
syndrome is depression. Psychiatric manifestations can precede the onset of full
blown Cushing's syndrome and therefore be misdiagnosed. Despite the fact that
treatment of the underlying endocrine disease in most cases alleviates
psychiatric symptoms, the loss of brain volume persists. CONCLUSIONS: It is
important to be alert to the symptoms of hypercortisolism in psychiatric patients
to avoid misdiagnosis and enable them receiving adequate treatment.
PMID- 26417793
TI - "Claw your way"--Machiavellianism among the medical community.
AB - BACKGROUND: Machiavellianism is a personality trait characterized by emotional
detachment and tendency to manipulate others to achieve one's own goal. It is
presumed that people high in Machiavellianism would more likely choose business
related occupations, whereas low Machiavellians would prefer helping professions,
therefore medical professionals are expected to be low-Machs. SUBJECTS AND
METHODS: This is a questionnaire study on 509 respondents: medical school
candidates (16.1%), medical students (65%), medical trainees (9.8%), residents
(6.3%) and specialists (2.8%) aimed at assessing the level of Machiavellianism,
as measured with Mach-IV score, a self-report questionnaire. RESULTS: The overall
mean Mach-IV score was 59.24+/-6.07. The highest mean Mach-IV score, 61.80+/
6.94, was found in the group of medical school candidates. The lowest mean Mach
IV score, 57.61+/-7.88, was reported in the group of registered specialists. Male
gender was found to be positively correlated with the mean Mach-IV score, which
in women was 58.97+/-6.08 and in men it was 60.16+/-6.01. There was a negative
correlation between the mean Mach-IV score and the age of post-graduate
participants. When we divided all participants into subgroups of "low Machs" (<60
points) and " high Machs" (>=60 points), we found that both subgroups were
similarly numerous--49.5% and 50.5%, accordingly. The highest representation of
"high Machs" was found in the subgroup of medical studies candidates (65.85%),
then in the students (47.73%) and in the group of post-graduates (45.16%). Gender
differences remained statistically significant--47.33% of women and 60.18% of men
were "high Machs". CONCLUSIONS: Machiavellianism level among medical candidates,
students and doctors is relatively high, however is gradually decreasing with the
progress of career.
PMID- 26417794
TI - Efficacy of LAI in first episode psychosis: an observational study--clinical
reports.
AB - The use of antipsychotics, especially second generation antipsychotics,
represents the milestone treatment of "first episode of psychosis" (FEP).
Although prodromal symptoms of psychosis have long been recognized, the clinical
management of psychotic disorders conventionally begins at the first episode of
frank psychosis, as it is well acknowledged that "duration of untreated
psychosis" (DUP) is one of the main factor that negatively affects prognosis: a
longer DUP is highly correlated to reduced response to treatment, poor clinical
and social outcomes, and an overall worst prognosis. Long-acting injectable (LAI)
formulations of antipsychotics have traditionally been used for those patients
with psychosis with the most severe symptoms, poorest compliance, most
hospitalizations and poorest outcomes; moreover it seems that psychiatrists tend
to prescribe LAI at the latter stages of the disease. We retrospectively
collected clinical and sociodemographic data regarding patients consecutively
presenting with symptoms of FEP attending the Community Mental Health Service
(CMHS) in Foggia from 1st June 2014 to 31st May 2015. We selected patients who
attended the CMHS in Foggia with symptoms of FEP. Different scales were
administered to assess symptoms severity, quality of life, side effects,
adherence, and overall functionality. In our sample LAI treatment was found to be
effective in treating symptoms associated to FEP, improved quality of life and it
was associated with a clinically irrelevant incidence of extrapyramidal side
effect. Considering that achieving a full symptoms remission in people affected
by FEP is associated to better outcomes, and that DUP is associated to poor
prognosis, LAIs could play an important role in improving overall recovery.
PMID- 26417795
TI - A National Snapshot of Substance Misuse among Child and Adolescent Psychiatric
Inpatients in Malta.
AB - This paper reports on a patient record survey that was undertaken with the
central aim of establishing reliable, baseline information to inform strategic
planning and organisation of future CAMHS in Malta. The records of the total
population of children and adolescents admitted into the psychatric hospital over
a five year period were surveyed. Results showed that the characteristics and
circumstances of children and adolescents with mental disorder and comorbid
substance misuse in Malta are similar to those described in international
studies. The survey emphasised the pressing need for further research into this
sub group and also highlighted gaps in reliable data systems locally.
PMID- 26417796
TI - HoNOSCA in an adolescent psychiatric inpatient unit: an exploration of outcome
measures.
AB - Routine Outcome Measures (ROM) are important tools, increasingly used to assess
both patient progress and service-provider efficacy. The Health of the Nation
Outcome Scales for Children and Adolescents (HoNOSCA) is a clinician- and patient
rated ROM which summarises a patient's global functioning within behaviour,
impairment, symptoms and social domains. Recent literature suggests that
consistent disparity exists between the patients' self-ratings and the
clinicians' ratings on HoNOSCA. We analysed HoNOSCA data for our own adolescent
inpatient unit and report similar findings. Studies have also shown significant
differences in both physical and mental health outcomes based on the patient
clinician dynamic and effective communication. We thus investigated the
predictive utility of the two HoNOSCA scores, and the disparity between them,
with respect to other outcomes measures (CGAS, length of stay and improvement on
HoNOSCA). HoNOSCA disparity scores were significantly associated with both
patient- and clinician-rated HoNOSCA improvement scores. Moreover, higher
admission HoNOSCA scores were associated with greater HoNOSCA improvement scores,
for both patient and clinician ratings. We report admission and discharge HoNOSCA
scores comparable to other child and adolescent psychiatric inpatient facilities.
PMID- 26417797
TI - Personality characteristics of psychotic patients as possible motivating factors
for participating in group psychotherapy.
AB - BACKGROUND: This study aimed to examine the relationship between some personality
characteristics of patients diagnosed with psychotic disorders and the quality of
their engagement in psychodynamic group psychotherapy. Given that previous
research has shown that self-stigma is significantly negatively associated with
the engagement of patients, the measure of self-stigma was used as a correlate of
patients' motivation to participate in group psychotherapy. SUBJECTS AND METHODS:
A total of 48 outpatients (52.1% women; mean age 35.30 years) attending group
psychodynamic psychotherapy completed The Inventory of Personality Organization,
The Pathological Narcissism Inventory, The Measure of Parental Style, The
Relationship Questionnaire, and The Internalized Stigma of Mental Illness scale.
RESULTS: The findings showed that patients with higher levels of self-stigma have
unhealthy attachments styles, perceived their mothers' parental style as
indifferent and achieved greater scores on narcissistic vulnerability scale. They
are also are prone to primitive psychological defences, have poorly integrated
identity, and achieved lower scores on reality testing dimension. CONCLUSION:
Taking into account the limitations of this study, these findings may contribute
to improved understanding of the quality of participation and engagement of
psychotic patients in group psychotherapy, and may help to develop more effective
therapeutic approaches.
PMID- 26417798
TI - The Use of Psychotropic Drug Therapy in Borderline Personality Disorder: a Case
Report.
AB - It is estimated that around 75% of patients with Borderline Personality Disorder
(BPD) are prescribed psychotropic medication during their treatment course,
although this is not recommended as first line therapy. In the UK, there are no
guidelines to advise which drug treatments to use in BPD, however, numerous, but
mostly small scale studies, show evidence that different medications target
specific core symptoms. We report a case of a 25 year old woman with BPD, who has
received treatment with five different psychotropic medications. We go on to
assess not only the efficacy of these treatments in this individual case, but
also whether the use of these treatments is in line with best evidence according
to currently available research.
PMID- 26417799
TI - Training in sleep medicine among European early career psychiatrists: a project
from the European Psychiatric Association--Early Career Psychiatrists Committee.
AB - INTRODUCTION: Sleep disorders have a proven association with psychiatric illness.
Therefore, psychiatrists require appropriate training in diagnosing and treating
sleep disorders. To date, there is no data available in Europe on training in
sleep medicine for early career psychiatrists (ECP). AIMS: To identify the
availability of training in sleep medicine for psychiatric trainees across Europe
and to establish how confident doctors feel in treating these conditions.
METHODS: European-wide survey carried out by the European Psychiatric Association
(EPA)-Early Career Psychiatrists Committees. Representatives of ECPs from each
participating European country filled in a questionnaire about availability of
training in sleep medicine in their country. ECPs were also invited to fill out a
questionnaire at the EPA congress in Nice in 2013. RESULTS: 55 participants from
27 European countries responded. Only 24% had sleep medicine training mandatorily
included in their national training curriculum. A majority (60%) felt that the
quality of the training they received was either average or below average. 88%
felt either very or fairly confident in treating insomnia. However, when asked to
select the correct management options for insomnia from a provided list of six,
only 19% and 33% of respondents chose the two correct options. CONCLUSIONS: There
is a clear gap between the level of confidence and the clinical judgements being
made to treat insomnia among European ECPs. There is a definite need to improve
the availability and structure of sleep medicine training for psychiatric
trainees in Europe.
PMID- 26417800
TI - Telepsychiatry in Polish patients' and doctors' opinion.
AB - BACKGROUND: Telepsychiatry is a new method of medical care, using modern
communication technologies and electronic informations. It consists of web pages,
containing data about diseases and their treatment in the form of multimedia
libraries with video- and audiobooks. This research concerns verification of
knowledge and attitude to telepsychiatry amongst patients and psychiatrists.
SUBJECTS AND METHODS: An anonymous survey was conducted amongst 105 psychiatrists
aged 26-74, including 74 women and 31 men and 102 patients aged 21-79, including
61 women and 41 men. RESULTS: Research reveals that majority of patients never
met with the concept of 'telepsychiatry' and do not know what it means. However,
more than 50% of respondents answered positively to every question considering
the utility of telepsychiatry. Furthermore according to 18% it is possible to
replace eye-to-eye conversation by videoconferencing. Only 15% of doctors claim
to have an extensive knowledge on telepsychiatry, and 10% do not know what it
means. The vast majority of physicians perceive positive aspects of this method
of medical care, but 63% would not want general insertion of telepsychiatry.
Doctors are apprehensive of losing personal data and medical confidentiality, and
of the necessity of legal changes as well. CONCLUSION: The obtained results allow
us to conclude that Polish patients and doctors, regardless of their knowledge,
age, gender or disease, perceive advantages of telepsychiatry. In connection with
this, implementing this method into the Polish medical market makes sense and is
in accordance with both patients' and doctors' opinion. Based on our research, we
confirmed that there is a necessity of wider popularization of telepsychiatry in
Polish therapeutics.
PMID- 26417801
TI - Genetic of addiction: common and uncommon factors.
AB - Epidemiological studies strongly suggest that genetic factors operate at all
steps of addictions, including vulnerability to initiation, continued use, and
propensity to become dependent. Several studies have been popular to investigate
the relative contributions of genetic and environmental factors, including the
availability of and exposure to a substance, and shared and unique environments.
The genetic influence on addiction has proved to be substantial, and
heritabilities for most addictive disorders are moderate to high. In this work we
evaluate the current status of data that analyzed genetic contribution in
addictions.
PMID- 26417802
TI - Neurofeedback application in the treatment of autistic spectrum disorders (ASD).
AB - The aim of this paper is to describe neurofeedback (NFB) treatment in Autistic
spectrum disorder (ASD) children. There is no specific cure for autism and
therapeutic guidelines are directed to improve the quality of life of people with
autism by reducing the symptoms and by increasing their functioning.
Neurofeedback is a computerized method based on tracking electrical activity of
the brain (EEG) and giving a feedback about it. The method has been developed in
neurophysiological labs of scientific institutes in USA and has been used very
successfully for over last 20 years. It has proven its efficacy in practise, but
also in scientific and clinical research. During 2010 and 2011 neurofeedback
treatment was administered to 10 children (N=10, 7 males and 3 females) age range
4 to 7 years which have been diagnosed as autistic spectrum disorder (highly
functional) with an unspecific impairment of speech development and trouble
communicating. An evaluation of treatment was done according to estimation of
changes in functioning (parents, teachers and therapists' ratings and all other
experts that were monitoring the child before, during and after the treatment)
and tracking of changes in electrophysiology. The results have shown most changes
in behaviour (less aggressive, more cooperation, better communication), attention
span and sensory motor skills. According to the assessment of parents, teachers,
therapists and other experts all children have accomplished a certain degree of
improvement in the level of daily functioning. Our experiences in usage of
neurofeedback in Autistic spectrum disorder (ASD) children confirmed previous
data that this method can be applied to this category of patients.
PMID- 26417803
TI - Analisys of the therapeutic factors in the Therapeutic Community Podsused among
the war related diagnosis and the others.
AB - Therapeutic community/TC/ is a sociotherapeutic method that uses sociotherapeutic
and psychotherapeutic techniques for various mental disorders. In Croatia, during
and after the war many war veterans have been in treatment through TC and many of
them still participate in it. Majority of them were diagnosed with PTSD
diagnosis, but some of them also had other diagnosis, e.g. depression, paranoid
delusion, etc. In this paper we describe principles of TC that we use in Croatia
and we also try to find out which curative factors of TC are the most important
for this population. We applied semistructured intervju based on Yalom book of
practice and theory of psychotherapy to explore what factors do war veterans find
the most important and relevant for their resilience and better coping with
everyday issues.
PMID- 26417804
TI - Development of vocational training systems for patients with intellectual
disability in Poland.
AB - BACKGROUND: The problem of employment of people with intellectual disabilities is
present in many countries. The literature on this topic draws attention to the
fact that the improvement of the situation in this area is conditioned by changes
in government policies, practices of employers and adequate preparation to
undertake professional duties by persons with intellectual disabilities.
OBJECTIVE: The objective of this review was to explore the changes in vocational
rehabilitation forms in Poland. RESULTS: As one of the ways to solve this problem
since 1991 in Poland the so called Workshops of Vocational Therapy have been
created. According to the regulations the Workshops were designed for adults with
intellectual disabilities, aged over 16 years with a total incapacity of gaining
an employment, for which occupational therapy was a form of social
rehabilitation. The further step in this process was the establishment of
Vocational Activation Centers, with which high hopes were associated. They were
expected to be an intermediate link in the creation of career paths from
rehabilitation forms ultimately to open labor market. In practice it turned out
that the creation of these Centers in Poland has been too slow. CONCLUSIONS: This
raised the necessity to change the attitude from the concept of matching the
participant to work and to the new environment, which frequently ends as a
trauma, to the concept of matching jobs to people. New initiatives and new
rehabilitation programs are developed based on this attitude.
PMID- 26417805
TI - Audit of memory clinic practice against CCG guidelines: West Suffolk Hospital.
AB - INTRODUCTION: The memory service based in the West Suffolk has received increased
funding to deliver a high quality service against standards set by the Clinical
Commissioning Group (CCG). AIMS: This audit aims to examine if we are achieving
the standards set by the local CCG and to identify areas to improve the quality
of the service.We also aimed to assess information as to how many patients
referred had dementia. If they had a dementia suitable for possible anti-dementia
medication (such as dementia of Alzheimer's type, Alzheimer's mixed type or
atypical or Lewy body/ Parkinson's dementia) to ascertain if they were being
offered anti-dementia medication. METHODS: Retrospective analysis of 60 patients
from the memory service were analysed. The first 10 patients referred in
alternative months were selected for inclusion. Standards were based on targets
set by the CCG in terms of time needed to assess, diagnose, communicate diagnosis
to the GP and give post diagnostic advice. RESULTS: Patients in this memory
service were being seen 37 days (on average) after referral. Most patients
received a diagnosis at their initial assessment but some needed further
investigation to establish the diagnosis or the specific type of diagnosis. The
time for letters to be typed did not meet standards and letters were sent out on
average 23 days after patients were being seen. Post diagnostic advice was
delivered to most who received a diagnosis. CONCLUSIONS: Our service is offering
timely diagnosis to those referred to the memory service in line with national
guidelines.
PMID- 26417806
TI - Psychogenic speech disorder--a case report.
AB - BACKGROUND: Conversion (dissociative) disorder is a psychiatric disorder in which
somatic symptoms or deficits are present in the absence of a definable organic
cause. The etiology of this disorder is not yet fully understood. The most
characteristic presentations are: pseudosensory syndromes, pseudoseizures,
psychogenic movement disorders and pseudoparalysis. Psychogenic speech disorder
is a rare form of conversion (dissociative) disorder. The aim of present case
study is to complete the knowledge on this subject. SUBJECT AND METHODS: The
article presents a case of a fifty year old woman who developed psychogenic
disorder of speech after being degraded to a lower position at work. After
excluding organic background of observed symptoms, the diagnosis of conversion
(dissociative) disorder was stated and adequate therapy was implemented, within
the capabilities of the Ward. RESULTS: Partial remission of presented symptoms
was achieved as a result of psychopharmacotherapy and psychotherapy. CONCLUSIONS:
Before stating the diagnosis of conversion (dissociative) disorder, possible
somatic causes of the observed symptoms should be excluded. Special attention
should be drawn to the importance of studying the psychological and family
context of this case and the patient's difficulty to understand and accept that
produced symptoms might be triggered by a psychogenic factor.
PMID- 26417807
TI - Mental state and its psychophysical conditions in patients with acute leukaemia
treated with bone marrow transplantation.
AB - BACKGROUND: Acute leukaemia and bone marrow transplantation (BMT) as a method of
its treatment are great psychological stressors, which are responsible for
anxiety and depression in the group of patients. The aim of the study was to
assess the patients' mental state and its psychophysical predictors before and
after BMT. SUBJECT AND METHOD: The study was of a longitudinal and self
descriptive character. The questionnaires: LOT-R, AIS, Mini-Mac, CECS, RSCL and
HADS were filled by 60 patients with acute leukaemia before and after BMT.
RESULTS: There were no essential statistical differences between the severity of
anxiety and depression before and after BMT but the pattern and the power of
various mental state predictors changed in the course of the hospitalization.
Anxiety before transplantation was greater when the psychological stress and the
strategy of "anxious preoccupation" were stronger and the strategy of "fighting
spirit" and the level of generalized optimism were weaker. The factors explained
51% variations of anxiety before transplantation. After BMT 77% variations of
anxiety were explained, which were associated with a high level of distress at
the end of the hospitalization, higher level of anxiety before transplantation,
weaker strategy of "fighting spirit" before transplantation and stronger strategy
of "anxious preoccupation" after BMT. Before transplantation 36% variations of
depression were explained and estimated as weaker "fighting spirit" and worse
"global life quality". The essential predictors of depressive symptoms after
transplantation, explained by 81% variations of depression, were weaker "fighting
spirit" before transplantation, stronger "anxious preoccupation" after
transplantation, worse "global life quality" after transplantation and higher
level of anxious and depressive symptoms on admission to hospital. CONCLUSION:
The psychological and pharmacological interventions, which reduce anxiety,
depression and "anxious preoccupation" as well as enhance "fighting spirit",
should be introduced before BMT to improve the patients' mental state.
PMID- 26417808
TI - What evidence is there to show which antipsychotics are more diabetogenic than
others?
AB - BACKGROUND: The use of antipsychotic therapy has been proven to have an
association with the incidence of diabetes mellitus. The use of atypical
antipsychotics is shown to have a higher association, in contrast with typical
antipsychotics. Olanzapine and Clozapine appear to have the highest rates of
diabetes mellitus incidence, due to their tendency to affect glucose metabolism
compared with other antipsychotic drugs. In this research the main goal is to
understand which antipsychotic drugs are the most diabetogenic and to show the
mechanisms involved in the glucose metabolism dysregulations with special focus
on Olanzapine considering it is a very commonly prescribed and used drug
especially among patients with schizophrenia. METHODS: Our study is a literature
based research. For our research we reviewed 41 Pubmed published articles from
2005 to 2015. CONCLUSION: According to most of the literature, from all the
antipsychotics, Clozapine followed by Olanzapine appear to be the atypical
neuroleptics that most relate to metabolic syndrome and Diabetes. The basis for
this metabolic dysregulations appears to be multifactorial in origin and a result
of the drugs, environment and genes interaction.
PMID- 26417809
TI - Critical Analysis of Psychiatrists' Opinion in GP Referral letter.
AB - BACKGROUND: Primary and secondary care communication is the cornerstone of
patient's care. Proper dialogue should be established. The shared care protocol
was an attempt to try to fill gaps and build bridges. METHODS: A special form was
designed to collect information about psychiatrists' opinion on GPs' referral
letter to psychiatric services. It contained 14 items, each item was marked as
essential, can be included or irrelevant. This form was sent electronically to
psychiatrists in South Essex University NHS Trust. They are 98 in total. It was
inputted on Excel data sheet and was analysed. RESULTS: 44 psychiatrists
responded. All respondents agreed that reason for referral is essential. Concise
description of the condition, risks and current medication were rated as
essential in more than 90%. Past medical history, past psychiatric history and
current physical health were essential in 79%. DISCUSSION: All professionals
involved should participate in evaluating and refining communication.
Psychiatrists' opinion in GPs letters is paramount as they are the recipients and
their assessments and future management plan should be geared to address the GP's
concerns. This is shown clearly by the psychiatrists agreeing that reason for
referral should be included in all letters, followed by what the GP has already
done and what risks the patient presents. CONCLUSION: Improving communication
between health professionals, improves patient's care, saves time and money, and
in addition prevents duplication of investigation and procedures.
PMID- 26417810
TI - A Completed Cycle Audit of Psychiatric Discharge Summaries.
AB - BACKGROUND: Patients discharge summaries are important as they record a vital
miles stone in patients' care. Their accurate record improves patients' care and
clarifies communication between different health professionals. METHODS: 60
Discharge summaries from different consultant psychiatrists' case load were
audited. The results were analysed and presented with recommendations to improve
them a format was suggested. A reaudit of 62 discharge summaries was carried out
by the same team after three years in the same catchment area but the practice
has changed to inpatient and community. RESULTS: Improvement in most of the areas
audited occur in the reaudit which indicates the usefulness of audit in improving
clinical practice which a pivotal part of clinical governance. DISCUSSION: This
completed audit cycle has proven that clinical practice has been reviewed and
methods of improving it have been implemented. It has been noted that more items
were reviewed and added to the second cycle which should be condoned. CONCLUSION:
Discharge summaries are important clinical documents in secondary and primary
care communications. They are helpful for secondary care staff as they good
references for people in out of hours services and Accident and Emergency. Good
quality discharge summaries improve patients care and make it easy to manage
clinical risk.
PMID- 26417811
TI - Modern indications for the use of opipramol.
AB - Opipramol is considered as a pharmacological agent that does not fit the
classification taking into account the division of antidepressants,
antipsychotics and anxiolytics. It has a structure related to tricyclic
antidepressants but it has a different mechanism of action, i.e. binding to
sigma1 and to sigma2 sites. It has been regarded as an effective drug in general
anxiety disorders together with other agents like SSRI's, SNRI's, buspirone and
pregabalin for many years. It can however also be indicated in other conditions,
e.g. it may be used as a premedication in the evening prior to surgery, positive
results are also observed in psychopharmacological treatment with opipramol in
somatoform disorders, symptoms of depression can be significantly reduced in the
climacteric syndrome. The latest data from literature present also certain
dangers and side effects, which may result due to opipramol administration. Mania
may be induced not only in bipolar patients treated with opipramol, but it can be
an adverse drug reaction in generalized anxiety disorder. This analysis shows
however that opipramol is an important drug still very useful in different
clinical conditions.
PMID- 26417812
TI - The Prevalence of Body Dysmorphic Disorder in Patients Undergoing Cosmetic
Surgery: a Systematic Review.
AB - Body dysmorphic disorder (BDD) is a somatoform disorder characterised by a
distressing obsession with an imagined or slight appearance defect, which can
significantly impair normal day-to-day functioning. Patients with BDD often first
present, and are hence diagnosed, in cosmetic surgery settings. Several studies
have investigated the prevalence rate of BDD in the general population or have
done so for patients referring to cosmetic medical centers. To date, however, no
review has been undertaken to compare the prevalence in the general community
versus in a cosmetic surgery setting. Despite the lack of such a review it is a
commonly held belief that BDD is more common in patients seeking cosmetic
surgery. The current study aims to review the available literature in order to
investigate whether BDD is indeed more prevalent in patients requesting cosmetic
surgery, and if that is the case, to provide possible reasons for the difference
in prevalence. In addition this review provides evidence on the effectiveness of
cosmetic surgery as a treatment of BDD.
PMID- 26417813
TI - Cortisol as an indicator of hypothalmic-pitituary-adrenal axis dysregulation in
patients with panic disorder: a literature review.
AB - Dysregulation of hypothalamic-pituitary-adrenal axis (HPA) is seen in numerous
mental disorders. Data of HPA axis disturbance in panic disorder are
inconsistent. In panic disorder HPA axis hyperactivity has been observed with
elevated cortisol levels. However, hypocortisolism has also been noted. Salivary
cortisol as a biomarker of HPA-axis activity has received special attention. The
aim of this paper is to review the findings on cortisol levels in panic disorder.
PMID- 26417814
TI - Impulsivity in anxiety disorders. A critical review.
AB - BACKGROUND: Anxiety symptoms and disorders are common. High comorbidity between
anxiety and other psychiatric disorders has been observed in community. Still,
the relationship between impulsivity and anxiety disorders is controversial and
not well explored. MATERIAL AND METHODS: The aim of this paper is to review
measures of trait impulsivity in anxiety disorders. A literature review of the
theoretical bases of the relationship between anxiety disorders and impulsivity
is presented. RESULTS: Impulsivity is a key feature of numerous psychiatric
disorders. Traditional conceptualizations suggest that impulsivity might display
a negative relationship with anxiety. However, an association of impulsivity in
patients with anxiety disorders is present. Some studies support proposition that
anxiety may influence impulsivity in individuals with predisposition toward
behavioural disinhibition. CONCLUSION: There is a link between anxiety and
impulsivity in psychiatric patients characterized by problems with impulse
control (e.g. pathological gambling, self-harming behaviour, eating disorders),
mood disorders and anxiety disorders. Behavioural and pharmacological
interventions for decreasing impulsivity may effectively be used in the
treatment.
PMID- 26417815
TI - Impulsivity and Panic Disorder: an exploratory study of psychometric correlates.
AB - BACKGROUND: Impulsivity is associated with a wide variety of psychiatric
disorders. However, the relationship between anxiety and impulsivity is not well
explored. The objective of this study was to examine whether anxiety symptoms
correlate with impulsivity in patients with panic disorder. SUBJECTS AND METHODS:
We examined 21 psychotropic drug-naove patients with panic disorder recruited
from the outpatient setting. The severity of Panic Disorder was assessed with
Panic and Agoraphobia Scale (PAS)-clinical rating version. Impulsivity was
evaluated with Barratt Impulsiveness Scale, 11th version (BIS-11). RESULTS: Our
findings indicate the correlation between specific dimensions of impulsivity and
selected subscales of Panic and Agoraphobia Scale. The positive correlation
between attentional and non-planning dimensions of impulsivity, 'disability' and
'worries about health' in drug-naove patients with PD was observed. CONCLUSIONS:
The findings corroborate with the prior reports of higher impulsivity trait among
patients with anxiety disorders.
PMID- 26417816
TI - Rapid-onset agranulocytosis in a patient treated with clozapine and lamotrigine.
AB - BACKGROUND: Clozapine is the treatment of choice in drug-resistant schizophrenia.
Lamotrigine is a mood stabiliser recommended as combined treatment strategy in
clozapine-resistant patients. There are cases of late-onset agranulocytosis
reported in literature. Some are associated with clozapine or lamotrigine, others
with the combination of both. CASE REPORT: The article presents a case of rapid
onset agranulocytosis in a 60-year old clozapine-resistant patient, in whom
lamotrigine was introduced as potentiation strategy. Discontinuation of both
substances and GCSF treatment resulted in normalization of the absolute
neutrophil count. CONCLUSIONS: The case suggests a possibility of developing
rapid-onset agranulocytosis in clozapine-resistant patients who require
lamotrigine as augmentation strategy. This emphasises the significance of
monitoring a patient's blood count and early management of any dyscrasias
noticed.
PMID- 26417817
TI - Psychological distress and social factors in patients with asthma and chronic
obstructive lung disease.
AB - Chronic respiratory diseases which embrace asthma and chronic obstructive
pulmonary disease (COPD) are common in the population. In a large number of cases
they are diagnosed very late. Statistics of deaths, especially in the case of
COPD, are underestimated because morbidity and mortality can be affected by other
comorbid conditions, for example cardiovascular disease. Asthma and COPD impair
not only physical functioning of patients but also affect their psychological
state. Mood disorders and cognitive function impairment are more often observed
in this group than in the general population. It has been proven that the
coexistence of psychological dysfunction significantly worsens the functioning of
patients (affects, among others, their work, family and social lives) and has an
impact on the course of the treatment of the somatic illness. First of all,
patients with cognitive deficits have greater problems in applying treatment
recommendations. Accordingly, it seems to be important to pay more attention to
the problem of mental disorders in patients with obstructive lung diseases. There
is a clear need for a multidisciplinary approach that will enable prevention,
early detection and effective treatment of the psychological disorders in that
group of patients.
PMID- 26417818
TI - Need for a Comprehensive Sex and Relationship Education Programme for Adults with
Learning Disability.
AB - INTRODUCTION: Most people with learning disabilities (PWLD) have little
understanding of the concept of sex and relationship. PWLD are vulnerable and
more likely to be victims of sexual offending. Currently, the only formal access
to sex and relationship education that PWLD have is in special need schools.
BACKGROUND: The right to express their sexuality is frequently restricted or
denied by restricted policies, negative attitudes and lack of awareness of their
needs. AIMS: To provide a Comprehensive Sex and Relationship Education programme
for PWLD. METHODOLOGY: These group/individual sessions will led by a sexuality
support worker with experience in working with PWLD. They will be supported by
members of the multidisciplinary team including, psychiatrist, psychologist,
occupational therapists etc. CONCLUSION: Providing sex and relationship education
PWLD would help them achieve a fulfilling and rewarding sexual experience and
make them less vulnerable to sexual abuse. There should be greater emphasis to be
placed on sex and relationship education in PWLD; preferably by qualified
professionals.
PMID- 26417819
TI - Medical Record Documentation in a Learning Disability In-patient Unit.
AB - INTRODUCTION: Consistency in clinical structure and content is an important
aspect of clinical practice. The rising demands on healthcare systems and
associated costs require a much more efficient and transparent means of recording
and accessing reliable clinical information in order to manage and deliver good
quality care to patients. AIMS: The audit has been completed with an aim to
highlight the local standards set for medical record documentation and to assess
if the outlined standards are being met in a learning disability in-patient
psychiatric setting, the Coppice. METHODOLOGY: Criteria based on GMC Good Medical
practice guidelines (2013), RCPsych Good Psychiatric Practice (2009) and Records
Management Policy. CONCLUSIONS: Good practice was maintained for most parameters.
Mild inaccuracies were noted with date of birth/ward name, timing and signatures.
RECOMMENDATIONS: This was presented locally and measures put in place to address
the gaps. A re-audit should be performed within a year in order to complete the
audit cycle and to ensure that the recommendations and action plan have been
followed through.
PMID- 26417821
TI - How can we make the current UK psychiatric training scheme truly trainee centred?
AB - INTRODUCTION: UK Psychiatric training is popular worldwide and IMG from
throughout the world come to UK. Psychiatric training has undergone significant
changes but this has not reflected in the outcomes. There is a need to refocus on
trainee centred teaching principles. CURRENT PSYCHIATRIC TRAINING: Current
training scheme started in 2007 as run-through programme spanning six years. Till
2005, examinations decided the progression of trainees through the training
scheme with development of Work Place Based Assessments. Following Tooke's
report, training was uncoupled and examinations regained importance in deciding
the progress of trainees to higher training. FACTORS AFFECTING PSYCHIATRIC
TRAINING: EWTD, budget cuts, service priorities lead to a sense of lack of
importance among trainees. Surveys focussing on clinical supervision pointed to
the inadequacy and poor quality of supervision. Training has lost trainee
centeredness. It is important to make the training maximally effective to deliver
safer services. Trainees are major work forces and the future consultants who
lead and manage services. CONCLUSION: Student centred teaching is a highly
skilled educational process. Adapting these principles into psychiatric training
could help trainees learn successfully.
PMID- 26417822
TI - Evaluation of a Specialised Counselling Service for Perinatal Bereavement.
AB - OBJECTIVES: We aimed to evaluate the outcomes of Petals: a charitable
organisation in Cambridgeshire. Petals provides counselling for women and couples
who have suffered perinatal bereavement, or trauma during pregnancy or birth.
This paper attempts to evaluate the effect of counseling interventions at this
difficult time. METHODS: Outcomes were recorded in 107 patients using the CORE
(Clinical Outcomes in Routine Evaluation) system. CORE was developed to assess
the effectiveness of psychological therapies. CORE-OM (CORE Outcome Measure)
involves a questionnaire that assesses subjective well-being, symptoms/problems,
function, and risk to self and others. The CORE-OM questionnaire was completed
before and after the counselling sessions. RESULTS: The CORE-OM scores were
summated into a global representation of severity. Severity decreased in all
patients. Symptoms of psychological pathology were also decreased in all cases.
CONCLUSION: Offering a free specialised counselling for parents suffering
perinatal loss seems to be associated with an improvement in psychological
outcomes. It is possible that it is more effective among a clinical population.
However, we are uncertain of the natural history of the psychological problems
this group of clients are experiencing. Having a control group would show how
much of any natural improvement is due to the therapy; conversely, it is possible
that without intervention these problems worsen with time, so a control group
could actually amplify the effect.
PMID- 26417820
TI - Pro Re Nata (PRN) prescription in an Inpatient Low Secure Learning Disability
Unit.
AB - INTRODUCTION: Pro Re Nata (PRN) prescribing in psychiatry is a common and
valuable facility to be used in acutely distressed patients. It is open to misuse
and PRN prescribing may be unnecessary/inappropriate. AIM: The aim of the audit
is to ensure safe and effective prescription of PRN medication. AUDIT STANDARDS:
The standards were set in congruence with the guidance from the local trust
policy. METHODOLOGY: All of the inpatient records at Wood Lea clinic were studied
over a 2 month period. CONCLUSIONS: Most of the standards against which the
clinical notes were assessed gave evidence of good medical practice. Patient
demographics demonstrated a 100% record of the NHS number but the patient's name
and ward fell short. RECOMMENDATIONS: This was presented locally and measures put
in place to address gaps. Re-audit should be performed within a year in order to
complete the audit cycle and to ensure that recommendations/action plan have been
followed through.
PMID- 26417823
TI - Should measurement of cognition be part of recovery programs for patients with
Psychotic Illness?
AB - The recovery model of schizophrenia is central to the devlopment of community
services for patients with schizophrenia. However often when applying the
recovery model of psychosis, often formal identification of cognitive imparements
is not carried out, nor are interventions to improve cognitive functioning
offered in a targeted way. Here we discuss how these issues relate to each other
and argue for the use of cognitive testing in order to elp recovery in
schizophrenia.
PMID- 26417824
TI - A review of the evidence for the use of metformin in the treatment of metabolic
syndrome caused by antipsychotics.
AB - BACKGROUND: Psychiatric patients requiring therapy with antipsychotics have a
greater incidence of becoming overweight or obese compared with the general
population. Many of these patients are often treated with second-generation
(atypical) antipsychotics (SGAs), which are associated with weight gain,
dyslipidaemia, and other metabolic derangements. The most important and first
line of treatment for the metabolic syndrome is lifestyle changes including diet
and exercise. However, other approaches like the use of medication (e.g.
Metformin) have been also used, mainly when the lifestyle changes are difficult
to achieve. Therefore, the treatment of antipsychotic-induced weight gain with
metformin may be an option after the lifestyle and dietary changes fail. The use
of metformin is still experimental and off license regarding the treatment of
metabolic syndrome in Psychiatric patients, however we wished to assess the
evidence for its use. METHODS: Our study is a literature based research. For our
research we reviewed 12 Pubmed published articles from 2006 to 2013. CONCLUSION:
Metformin have been reported to counteract effectively antipsychotic-induced body
weight gain and has been demonstrated to improve glycaemic control and promote a
moderate weight loss in both diabetic and non-diabetic subjects. Metformin use
appears to be a benefit when started early in the course of treatment and mostly
in young adults newly exposed to antipsychotic drugs.
PMID- 26417825
TI - Factors influencing the levels of work engagement in physicians from Poland,
Serbia and Bulgaria.
AB - INTRODUCTION: Lowered work engagement and burnout are a growing problem in recent
years, especially among physicians. Cynicism, lack of energy and decreased
efficacy may lead to the occurrence of severe depression. These phenomena
influence almost every aspect of affected person's life, both professional and
extraprofessional, and decrease its quality. The aim of our study was to evaluate
the influence of family life and other factors on levels of work engagement and
risk of depression. MATERIALS AND METHODS: Our study was conducted on a group of
417 physicians from Poland, Serbia and Bulgaria using a paper questionnaire. The
collected data was subjected to statistical analyses using Statsoft Statistica v.
10.0 software. RESULTS: There was no significant correlation between work
engagement and sex or age. The highest score on work engagement was in Serbia
(m=4.41; Mann-Whitney's U test with p<0.05). The highest score of BDI was in
Bulgaria (m=14.73; Mann-Whitney's U test with p<0.05). There was no significant
correlation exceeding r=0.5 between UWES and SWING scales. WHI+/WHI- ratio
correlates significantly with a BDI scale (Spearman's r=-0.49; p<0.05).
CONCLUSIONS: Family life of physicians seem to have minor or even no influence on
their work engagement and risk of burnout. The negative influence of work on
family life may increase the risk of depression, and that effect is not
susceptible to either positive or negative interactions of family life with work.
The country with the lowest expenditure on a healthcare have also the lowest
levels of work engagement.
PMID- 26417826
TI - PROMISE. Beyond frontiers.
AB - The concepts underlying the PROMISE initiative are described. This initiative to
implement more humane healthcare is now developing from a local initiativein
Cambridge to a global movement.
PMID- 26417827
TI - Teenage pregnancy: a psychopathological risk for mothers and babies?
AB - INTRODUCTION: Teen pregnancy remains a public health problem of varying
importance in developing and developed countries. There are risks and
consequences for teen parents and the child on the medical and socioeconomic
level. METHOD: We conducted a literature search on multiple databases, focusing
on the risk and the consequences of teen pregnancy and childbearing. We used
different combined keywords as teen pregnancy, teen mother, teenage parents,
teenage childbearing, teenage mother depression. Our search included different
type of journals to have access on different views (medical, psychological,
epidemiologic). RESULTS: The teen mothers are more at risk for postnatal
depression, school dropout and bad socioeconomic status. The babies and children
are more at risk for prematurity and low birthweight and later for developmental
delays and behavior disorders. CONCLUSIONS: Pregnancy in adolescence should be
supported in an interdisciplinary way (gynecologist, psychologist, child
psychiatrist, midwives, pediatrician). We need further studies that allow
targeting patients most at risk and personalizing maximum support.
PMID- 26417828
TI - Hypothalamus-Pituitary-Adrenal Axis, Hair Cortisol and the Metabolic Syndrome.
AB - In this paper we discuss the possibility of using Hair Cortisol in Clinical
Practice to monitor HPA status in patents at risk of developing the Metabolic
Syndrome, and also its possible use to assess effectiveness of the effectiveness
of treatment in patients with the Metabolic Syndrome.
PMID- 26417829
TI - Palliative Care in Dementia.
AB - The Dementias are common neurodegenerative diseases which gradually deteriorate
and eventually become fatal. However, hospice care is usually made available to
patients suffering from Cancer, while patients who suffer from other chronic
conditions such as dementia are not usually offered such care. However the
lessons which have been learnt regarding hospice palliative care could be applied
with some modification to the care of patients with Dementia. This article
attempts to discuss the present literature about palliative care in Dementia, in
order to clarify the evidence which underlies the European Association for
Palliative Care 'White paper defining optimal palliative care in older people
with dementia'.
PMID- 26417830
TI - Views from GP and Psychiatric trainees about getting experience in each other's
specialty during training: A way to develop a shared culture?
AB - The need to deliver holistic medical care that addresses both physical and mental
health requirements has never been more important. The UK medical training system
has been designed to provide all medical graduates with a broad experience of
different medical specialities and psychiatry prior to entering specialist
training. Furthermore there is a distinct crossover between Psychiatric and
General Practice training, with programmes providing trainees with the
opportunity to work alongside each other in the care of mental health patients.
The video presentation will explain the UK medical training system in more
detail, before going on to explore how the organisation of training may foster a
shared culture among different specialities and how it could form a model for
improving parity of esteem of medical and physical health care. In addition it
will discuss the strengths and weaknesses of this system from a trainee
perspective and will conclude with comments from eminent Psychiatrists whom have
special interests in medical training and developingparity of mental and physical
health care.
PMID- 26417831
TI - 'Dar Kenn Ghal Sahhtek'--an eating disorder and obesity service in Malta.
AB - This paper will describe the incidence of eating disorders, with particular focus
on obesity and binge eating, within the Island of Malta. The development of and
'Dar Kenn Ghal Sahhtek', the first centre for eating disorders in Malta will then
be recounted, and the effective therapeutic interventions provided in it will be
described. One important function of this unit is the treatment of excessive
obesity. Some epidemiological data on the Obese Patients in DKS, relating to the
incidence of Binge Eating Disorder in the DKS patient group will be given. This
data was collected during a collaboritive research project between the Psychiatry
Department of Cambridge University and 'Dar Kenn Ghal Sahhtek'.
PMID- 26417832
TI - Transcranial magnetic stimulation (TMS) in Attention Deficit Hyperactivity
Disorder (ADHD).
AB - Attention Deficit Hyperactivity Disorder (ADHD) is a common neuropsychiatric
disorder, which affects children as well as adults and leads to significant
impairment in educational, social and occupational functioning and has associated
personal and societal costs. Whilst there are effective medications (mostly
stimulants) as well as some psychobehavioural treatments that help alleviate
symptoms of ADHD, there is still need to improve our understanding of its
neurobiology as well as explore other treatment options. Transcranial Magnetic
Stimulation (TMS) and repetitive transcranial magnetic stimulation (rTMS) are
safe and non-invasive investigative and therapeutic tools respectively. In this
short article, I will explore their potential for improving our understanding of
the neurobiology of ADHD as well consider its as a possible treatment option.
PMID- 26417833
TI - The girl who would not sit--case report.
AB - A 21 year old girl presented with severe fear of contamination leading to 11
hours of cleaning per day and refusal to sit down anywhere except at home or in
mother's car. She also had a moderate depressive episode secondary to social
stressors and further isolation due to her lack of time to socialize as cleaning
was her priority. She was supported according to the biopsychosocial model of
care i.e. An antidepressant (Sertraline), 1:1 psychology and alternative housing
away from precipitating and perpetuating stressors. She improved significantly
over 6 months, but the cultural issues and stigma continued to hinder the longer
term care plans. The importance of understanding the beliefs and customs of the
Travellers' community is highlighted with this case report.
PMID- 26417834
TI - Why hasn't studying perception in autism spectrum disorders helped us create a
cognitive model?
AB - There are a number of cognitive models of autism that aim to explain how mental
processes are handled differently in the condition. These models make claims
about the nature of cognitive function in people with autism, and suggest that
these differences applied in social contexts lead to the characteristic
behavioural patterns. However, it is difficult to study these cognitive
differences directly because of the complexity of social situations. Studies of
perceptual function are tempting as an alternative way to study cognition because
it is far easier to control the conditions and the stimuli that participants are
exposed to. This makes hypothesis generation and interpretation of results more
objective and more convincing. However, the study of perception in autism hasn't
been very productive in contributing towards a model of cognition in autism. In
many areas there are studies reporting contradictory results, preventing arrival
at a consensus about the largest unresolved issues in the area. These studies
tend to be repeated multiple times, but continue to provide contradictory
evidence that doesn't allow us to place confidence in any of the cognitive
models. An approach to these issues is proposed, focusing on critical analysis of
contradictory studies rather than the endless process of repetition. This allows
previous studies to be interpreted more objectively and resolve conflicts, and
guides the design of future studies in ways that avoid the pitfalls that have
been identified. Both of these outcomes result in more productive work being
done. The first example is in the study of motion perception in autism, where the
use of non-identical stimuli has been problematic. On closer critical analysis, a
fundamental aspect of the motion stimuli demonstrates that the contradictions
might be expected based on the differences in stimuli used. Addressing this issue
can move the field towards resolution. A second example is in the study of
spatial frequency sensitivity. Here, poor study design has created results
leading to an "eagle-eyed visual acuity" hypothesis of autism. Errors in the
initial study are revealed, suggesting that the model should be abandoned.
Finally, a general issue is the assumption of homogeneity of perceptual ability
and genetics in autism, where the reality is that subgroups exist within the
population of people with autism, and significant variation exists between them.
The evidence for this is summarised and the issues that it creates explored.
PMID- 26417835
TI - Effect of natriuretic peptides on cerebral artery blood flow in healthy
volunteers.
AB - The natriuretic peptides (NPs), atrial natriuretic peptide (ANP), brain
natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), have vasoactive
functions that concern humans and most animals, but their specific effects on
cerebral circulation are poorly understood. We therefore examined the
responsiveness of cerebral arteries to different doses of the natriuretic
peptides in animals and humans. We conducted a dose-response experiment in guinea
pigs (in vitro) and a double-blind, three-way cross-over study in healthy
volunteers (in vivo). In the animal experiment, we administered cumulative doses
of NPs to pre-contracted segments of cerebral arteries. In the main study, six
healthy volunteers were randomly allocated to receive two intravenous doses of
ANP, BNP or CNP, respectively, over 20 min on three separate study days. We
recorded blood flow velocity in the middle cerebral artery (VMCA) by transcranial
Doppler. In addition, we measured temporal and radial artery diameters, headache
response and plasma concentrations of the NPs. In guinea pigs, ANP and BNP but
not CNP showed significant dose-dependent relaxation of cerebral arteries. In
healthy humans, NP infusion had no effect on mean VMCA, and we found no
difference in hemodynamic responses between the NPs. Furthermore, natriuretic
peptides did not affect temporal and radial artery diameters or induce headache.
In conclusion, natriuretic peptides in physiological and pharmacological doses do
not affect blood flow velocity in the middle cerebral artery or dilate
extracerebral arteries in healthy volunteers.
PMID- 26417836
TI - Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) levels in patients
with overt and subclinical hyperthyroidism: effects of treatment.
AB - BACKGROUND AND OBJECTIVES: Signal peptide-CUB-EGF domain-containing protein 1
(SCUBE1) has been shown to increase in parallel with platelet activation in acute
ischaemic and thrombotic diseases. There has been no study evaluating SCUBE1
levels in patients with overt hyperthyroidism (OHyper) and subclinical
hyperthyroidism (SHyper), conditions which are known to show impairment of both
endothelial and platelet function. This study sought to evaluate SCUBE1
concentrations in patients with SHyper and OHyper, and assessed the effects of
antithyroid drug (ATD) therapy on circulating SCUBE1 levels. DESIGN AND METHODS:
Forty-five untreated patients with OHyper, 20 untreated patients with SHyper and
30 age- and sex-matched healthy controls were prospectively included in the
study. Biochemical and hormonal parameters were evaluated in all patients before
and after treatment. RESULTS: Compared with the control subjects, SCUBE1 levels
were significantly increased in patients with SHyper and OHyper (P < 0.0001 and P
= 0.002, respectively). SCUBE1 levels were not significantly different in
patients with OHyper compared with patients with SHyper. There was no significant
correlation between serum thyroid hormones and SCUBE1 levels. Plasma SCUBE1
levels decreased significantly in both OHyper and SHyper after ATD treatment (P <
0.05). CONCLUSIONS: Increased SCUBE1 levels in both SHyper and OHyper patients
may reflect increased platelet activation and possible endothelial dysfunction,
which might augment the risk for atherosclerotic and atherothrombotic
complications. SCUBE1 may be used as a reliable marker of endothelial damage in
hyperthyroidism, especially in the subclinical period.
PMID- 26417837
TI - Intramolecular Conjugate Ene Reaction of gamma-Difluoromethyl- and gamma
Trifluoromethyl-alpha,beta-Unsaturated gamma-Butyrolactones.
AB - A general synthetic strategy to cis-fused bicyclic gamma-butyrolactones via the
retro-Diels-Alder reaction/intramolecular conjugate ene cascade (RDA/ICE)
reaction under the flash-vacuum pyrolysis of maleic anhydride adducts is
developed. The reaction gave high yields of products with high stereoselectivity.
The existence of the difluoromethyl or trifluoromethyl group at the gamma
position of the in situ-generated homoalkenyl- or homoalkynyl-alpha,beta
unsaturated gamma-butyrolactones was found to accelerate the rate of the
intramolecular conjugate ene reaction leading to gamma-difluoromethylated and
gamma-trifluoromethylated cis-fused bicyclic gamma-butyrolactones.
PMID- 26417838
TI - Erratum: Theoretical analysis of excited states and energy transfer mechanism in
conjugated dendrimers.
PMID- 26417840
TI - Accuracy of plasma interleukin-18 and adiponectin concentrations in predicting
metabolic syndrome and cardiometabolic disease risk in middle-age Brazilian men.
AB - The aims of this cross-sectional study were to explore the ability of serum
interleukin 18 (IL-18) and adiponectin to identify metabolic syndrome (MetS), and
to verify their association with an index of central lipid overaccumulation
(lipid accumulation product (LAP)) and cardiometabolic risk factors in a
population of middle-aged Brazilian men. A group of 218 apparently healthy middle
aged Brazilian men (age, 50.3 +/- 4.97 years) underwent anthropometric, clinical,
sociodemographic, and standard serum biochemical assessments. LAP was calculated
and the study participants were categorized into 3 groups according to serum IL
18 and adiponectin cut-points tertiles to verify the association of these
biomarkers with cardiometabolic risk factors. The MetS group had more less active
(p = 0.03) and obese (p < 0.01) individuals who exhibited higher IL-18 (p < 0.01)
and lower adiponectin (p < 0.01) than did those in the group with no MetS. After
adjustments (age, smoking, alcohol consumption, physical activity level, and
total body fat), serum IL-18 >= 336.4 pg/mL was an independent factor for MetS
occurrence and it was directly associated with LAP (>=51.28), central obesity,
hypertriglyceridemia, and hypertension (p < 0.05), but not with high-density
lipoprotein cholesterol (HDL-C). Serum adiponectin >= 7.02 MUg/mL was negatively
associated with MetS occurrence, LAP, hypertriglyceridemia, and low HDL-C (p <
0.05), but not with central obesity and hypertension. In conclusion, both IL-18
and adiponectin demonstrated the ability to identify MetS in this population,
with IL-18 being more accurate. The association of these biomamarkers with LAP
and cardiometabolic risk factors highlights its relevance as a diagnostic tool.
PMID- 26417841
TI - Predicted 10-year risk of cardiovascular disease among Canadian adults using
modified Framingham Risk Score in association with dietary intake.
AB - Initial risk assessment to estimate 10-year risk of cardiovascular disease (CVD)
is completed by Framingham Risk Score (FRS). In 2012 2 modifications were added
to FRS by the Canadian Cardiovascular Society: FRS is doubled in subjects aged 30
59 years who have CVD present in a first-degree relative before 55 years of age
for men and 65 years of age for women; and cardiovascular age is calculated for
each individual. Our aim was to implement these modifications and evaluate
differences compared with traditional FRS. Further, we evaluated the association
between dietary intake and 10-year risk. The Canadian Health Measures Survey data
cycle 1 was used among participants aged 30-74 years (n = 2730). Descriptive and
logistic regression analyses were conducted using STATA SE 11. Using modified FRS
for predicting 10-year risk of CVD significantly increased the estimated risk
compared with the traditional approach, 8.66% +/- 0.35% versus 6.06% +/- 0.18%,
respectively. Greater impact was observed with the "cardiovascular age"
modification in men versus women. The distribution of Canadians in low- (<10%)
and high-risk (>=20%) categories of CVD show a significant difference between
modified and traditional FRS: 67.4% versus 79.6% (low risk) and 13.7% versus 4.5%
(high risk), respectively. The odds of having risk >=10% was significantly
greater in low-educated, abdominally obese individuals or those with lower
consumption of breakfast cereal and fruit and vegetable and greater potato and
potato products consumption. In conclusion, the traditional FRS method
significantly underestimates CVD risk in Canadians; thus, applying modified FRS
is beneficial for screening. Additionally, fibre consumption from fruit and
vegetable or breakfast cereals might be beneficial in reducing CVD risks.
PMID- 26417842
TI - How does the VPD response of isohydric and anisohydric plants depend on leaf
surface particles?
AB - Atmospheric vapour pressure deficit (VPD) is the driving force for plant
transpiration. Plants have different strategies to respond to this 'atmospheric
drought'. Deposited aerosols on leaf surfaces can interact with plant water
relations and may influence VPD response. We studied transpiration and water use
efficiency of pine, beech and sunflower by measuring sap flow, gas exchange and
carbon isotopes, thereby addressing different time scales of plant/atmosphere
interaction. Plants were grown (i) outdoors under rainfall exclusion (OD) and in
ventilated greenhouses with (ii) ambient air (AA) or (iii) filtered air (FA), the
latter containing <1% ambient aerosol concentrations. In addition, some AA plants
were sprayed once with 25 mM salt solution of (NH4 )2 SO4 or NaNO3 . Carbon
isotope values (delta(13) C) became more negative in the presence of more
particles; more negative for AA compared to FA sunflower and more negative for OD
Scots pine compared to other growth environments. FA beech had less negative
delta(13) C than AA, OD and NaNO3 -treated beech. Anisohydric beech showed
linearly increasing sap flow with increasing VPD. The slopes doubled for (NH4 )2
SO4 - and tripled for NaNO3 -sprayed beech compared to control seedlings,
indicating decreased ability to resist atmospheric demand. In contrast, isohydric
pine showed constant transpiration rates with increasing VPD, independent of
growth environment and spray, likely caused by decreasing gs with increasing VPD.
Generally, NaNO3 spray had stronger effects on water relations than (NH4 )2 SO4
spray. The results strongly support the role of leaf surface particles as an
environmental factor affecting plant water use. Hygroscopic and chaotropic
properties of leaf surface particles determine their ability to form wicks across
stomata. Such wicks enhance unproductive water loss of anisohydric plant species
and decrease CO2 uptake of isohydric plants. They become more relevant with
increasing number of fine particles and increasing VPD and are thus related to
air pollution and climate change. Wicks cause a deviation from the analogy
between CO2 and water pathways through stomata, bringing some principal
assumptions of gas exchange theory into question.
PMID- 26417843
TI - A shift in paradigm towards human biology-based systems for cholestatic-liver
diseases.
AB - Cholestatic-liver diseases (CLDs) arise from diverse causes ranging from genetic
factors to drug-induced cholestasis. The so-called diseases of civilization
(obesity, diabetes, metabolic disorders, non-alcoholic liver disease,
cardiovascular diseases, etc.) are intricately implicated in liver and gall
bladder diseases. Although CLDs have been extensively studied, there seem to be
important gaps in the understanding of human disease. Despite the fact that many
animal models exist and substantial clinical data are available, translation of
this knowledge towards therapy has been disappointingly limited. Recent advances
in liver cell culture such as in vivo-like 3D cultivation of human primary
hepatic cells, human induced pluripotent stem cell-derived hepatocytes; and
cutting-edge analytical techniques such as 'omics' technologies and high-content
screenings could play a decisive role in deeper mechanistic understanding of
CLDs. This Topical Review proposes a roadmap to human biology-based research
using omics technologies providing quantitative information on mechanisms in an
adverse outcome/disease pathway framework. With modern sensitive tools, a shift
in paradigm in human disease research seems timely and even inevitable to
overcome species barriers in translation.
PMID- 26417844
TI - Prevalence of hypertriglyceridemic waist and association with risk of type 2
diabetes mellitus: a meta-analysis.
AB - INTRODUCTION: A meta-analysis of studies assessing the prevalence of
hypertriglyceridemic waist and an association with risk of type 2 diabetes
mellitus (T2DM). MATERIALS AND METHODS: PubMed, EMBASE, Web of Science, CNKI,
CQVIP and Wanfang databases were searched for studies of the prevalence of
hypertriglyceridemic waist or association with risk of T2DM. Reference lists of
each original article were also searched. A random-effects model was used to
synthesize the combined prevalence and odds ratios. Publication bias and
substantial heterogeneity were examined. RESULTS: Twenty-five eligible studies
involving 93 194 participants (93 194 for prevalence and 34 199 for odds ratios):
17 articles of prevalence, and 8 of both prevalence and risk of T2DM. Prevalence
of hypertriglyceridemic waist ranged from 4% to 47%, with pooled prevalence of
18% (95% CI 13-23%), overall: 18% (95% CI 13-23%) for men and 19% (95% CI 13-24%)
for women. Odds ratios ranged from 2.8 to 9.6 for T2MD in overall, with pooled
odds ratios of 4.18 (95% CI 3.55-4.92), overall: 3.55 (95% CI 2.93-4.31) for men
and 4.18 (95% CI 3.43-5.09) for women. DISCUSSION/CONCLUSION: The prevalence of
hypertriglyceridemic waist has reached an alarming level and is closely
associated with increased risk of T2DM in the general population, particularly
among women and among brown-skinned men and women.
PMID- 26417845
TI - Managing synchronous liver metastases from colorectal cancer: a multidisciplinary
international consensus.
AB - An international panel of multidisciplinary experts convened to develop
recommendations for managing patients with colorectal cancer (CRC) and
synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is
defined as liver metastases detected at or before diagnosis of the primary CRC.
Early and late metachronous metastases are defined as those detected ?12months
and >12months after surgery, respectively. To provide information on potential
curability, use of high-quality contrast-enhanced computed tomography (CT) before
chemotherapy is recommended. Magnetic resonance imaging is increasingly being
used preoperatively to aid detection of subcentimetric metastases, and alongside
CT in difficult situations. To evaluate operability, radiology should provide
information on: nodule size and number, segmental localization and relationship
with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver
condition and anticipated remnant liver volume. Pathological evaluation should
assess response to preoperative chemotherapy for both the primary tumour and
metastases, and provide information on the tumour, margin size and
micrometastases. Although the treatment strategy depends on the clinical
scenario, the consensus was for chemotherapy before surgery in most cases. When
the primary CRC is asymptomatic, liver surgery may be performed first (reverse
approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is
to downsize tumours to allow resection. Hepatic resection should not be denied to
patients with stable disease after optimal chemotherapy, provided an adequate
liver remnant with inflow and outflow preservation remains. All patients with
synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team.
PMID- 26417846
TI - Investigation of the cingulate cortex in idiopathic generalized epilepsy.
AB - OBJECTIVE: Studies using quantitative neuroimaging have shown subtle
abnormalities in patients with idiopathic generalized epilepsy (IGE). These
findings have several locations, but the midline parasagittal structures are most
commonly implicated. The cingulate cortex is related and may be involved. The
objective of the current investigation was to perform a comprehensive analysis of
the cingulate cortex using multiple quantitative structural neuroimaging
techniques. METHODS: Thirty-two patients (18 women, 30 +/- 10 years) and 36
controls (18 women, 32 +/- 11 years) were imaged by 3 Tesla magnetic resonance
imaging (MRI). A volumetric three-dimensional (3D) sequence was acquired and used
for this investigation. Regions-of-interest were selected and voxel-based
morphometry (VBM) analyses compared the cingulate cortex of the two groups using
Statistical Parametric Mapping (SPM8) and VBM8 software. Cortical analyses of the
cingulate gyrus was performed using Freesurfer. Images were submitted to
automatic processing using built-in routines and recommendations. Structural
parameters were extracted for individual analyses, and comparisons between groups
were restricted to the cingulate gyrus. Finally, shape analyses was performed on
the anterior rostral, anterior caudal, posterior, and isthmus cingulate using
spherical harmonic description (SPHARM). RESULTS: VBM analyses of cingulate gyrus
showed areas of gray matter atrophy, mainly in the anterior cingulate gyrus (972
mm(3) ) and the isthmus (168 mm(3) ). Individual analyses of the cingulate cortex
were similar between patients with IGE and controls. Surface-based comparisons
revealed abnormalities located mainly in the posterior cingulate cortex (718.12
mm(2) ). Shape analyses demonstrated a predominance of anterior and posterior
cingulate abnormalities. SIGNIFICANCE: This study suggests that patients with IGE
have structural abnormalities in the cingulate gyrus mainly localized at the
anterior and posterior portions. This finding is subtle and variable among
patients.
PMID- 26417848
TI - Effects of baffle configuration and tank size on spherical agglomerates of
dimethyl fumarate in a common stirred tank.
AB - To pave the way for technology transfer and scale up of the spherical
agglomeration (SA) process for dimethyl fumarate, effects of the US, European and
Kawashima type baffles and 0.5, 2.0 and 10 L-sized common stirred tank were
studied. It was found that the particle size distribution varied significantly.
However, the size-related properties such as dissolution profile and flowability
of agglomerates from the same size cut after sieving could remain unchanged. The
interior structure-related properties such as particle density and mechanical
property of agglomerates upon baffle change and scale up from the same size cut
were decayed and the agglomerates could become denser and stronger by prolonged
maturation time. To maintain the same size distribution, agglomerates from any
batch could have been separated and classified by sieving and then blended back
together artificially by the desired weight% of each cut.
PMID- 26417849
TI - Preparation and evaluation of lipid polymer nanoparticles for eradicating H.
pylori biofilm and impairing antibacterial resistance in vitro.
AB - The resistance of Helicobacter pylori to classical antimicrobial treatment has
become increasingly common, whereupon biofilms are considered to play an
important role in the resistance mechanism. Here 10.2% of amoxicillin (AMX) and a
novel anti H. pylori adhesion material pectin sulfate (PECS) loaded lipid polymer
nanoparticles (LPN) were prepared, with rhamnolipid and phospholipids as the
outer mixed lipids layer (RHL-PC-LPN). The size of RHL-PC-LPN was around 200 nm,
was negatively-charged, and showed sustained and complete drug release within
24h. In an in vitro study, H. pylori biofilm models were successfully
established. RHL-PC-LPN, superior to PC-LPN (employing phospholipids only as the
outer lipid layer), PECS+AMX (mixture of PECS and AMX) and AMX only, was proven
to significantly eradicate H. pylori in the biofilm form. In accordance to our
previous results, the RHL-PC-LPN group, together with the PC-LPN and PECS+AMX
group, inhibited H. pylori from adhering to AGS cells. Investigating the
underlying mechanisms contributing to the death of H. pylori caused by RHL-PC
LPN, we found that LPN could lower the antibiotic minimal inhibition
concentration (MIC) to biofilm form from 125 MUg/ml to 15.6 MUg/ml. Furthermore,
FITC-ConA labeled extracellular polymeric substances (EPS) were decreased in the
RHL-PC-LPN group observed by a laser scanning confocal microscope. Therefore, we
conclude that employing the mixed lipids of rhamnolipid and phospholipids as the
outer layer of nanoparticles and PECS as the inner core produces a system capable
of significantly disrupting H. pylori biofilm by eliminating the EPS as well as
inhibiting the adherence and colonization of bacteria.
PMID- 26417847
TI - Spatiotemporal patterns of cortical fiber density in developing infants, and
their relationship with cortical thickness.
AB - The intrinsic relationship between the convoluted cortical folding and the
underlying complex whiter matter fiber connections has received increasing
attention in current neuroscience studies. Recently, the axonal pushing
hypothesis of cortical folding has been proposed to explain the finding that the
axonal fibers (derived from diffusion tensor images) connecting to gyri are
significantly denser than those connecting to sulci in both adult human and non
human primate brains. However, it is still unclear about the spatiotemporal
patterns of the fiber density on the cortical surface of the developing infant
brains from birth to 2 years of age, which is the most dynamic phase of postnatal
brain development. In this paper, for the first time, we systemically
characterized the spatial distributions and longitudinal developmental
trajectories of the cortical fiber density in the first 2 postnatal years, via
joint analysis of longitudinal structural and diffusion tensor imaging from 33
healthy infants. We found that the cortical fiber density increases dramatically
in the first year and then keeps relatively stable in the second year. Moreover,
we revealed that the cortical fiber density on gyral regions was significantly
higher at 0, 1, and 2 years of age than that on sulcal regions in the frontal,
temporal, and parietal lobes. Meanwhile, the cortical fiber density was strongly
positively correlated with cortical thickness at several three-hinge junction
regions of gyri. These results significantly advanced our understanding of the
intrinsic relationship between the cortical folding, cortical thickness and
axonal wiring during early postnatal stages.
PMID- 26417850
TI - Atomic-level characterization of transport cycle thermodynamics in the glycerol-3
phosphate:phosphate antiporter.
AB - Membrane transporters actively translocate their substrate by undergoing large
scale structural transitions between inward- (IF) and outward-facing (OF) states
('alternating-access' mechanism). Despite extensive structural studies, atomic
level mechanistic details of such structural transitions, and as importantly,
their coupling to chemical events supplying the energy, remain amongst the most
elusive aspects of the function of these proteins. Here we present a
quantitative, atomic-level description of the functional thermodynamic cycle for
the glycerol-3-phosphate:phosphate antiporter GlpT by using a novel approach in
reconstructing the free energy landscape governing the IF<->OF transition along a
cyclic transition pathway involving both apo and substrate-bound states. Our
results provide a fully atomic description of the complete transport process,
offering a structural model for the alternating-access mechanism and
substantiating the close coupling between global structural transitions and local
chemical events.
PMID- 26417851
TI - Provision and consumption of alcohol-based hand rubs in European hospitals.
AB - Hand hygiene is considered to be the most effective way of preventing microbial
transmission and healthcare-associated infections. The use of alcohol-based hand
rubs (AHRs) is the reference standard for effective hand hygiene. AHR consumption
is a valuable surrogate parameter for hand hygiene performance, and it can be
easily tracked in the healthcare setting. AHR availability at the point of care
ensures access to optimal agents, and makes hand hygiene easier by overcoming
barriers such as lack of AHRs or inconvenient dispenser locations. Data on AHR
consumption and availability at the point of care in European hospitals were
obtained as part of the Prevention of Hospital Infections by Intervention and
Training (PROHIBIT) study, a framework 7 project funded by the European
Commission. Data on AHR consumption were provided by 232 hospitals, and showed
median usage of 21 mL (interquartile range (IQR) 9-37 mL) per patient-day (PD) at
the hospital level, 66 mL/PD (IQR 33-103 mL/PD) at the intensive-care unit (ICU)
level, and 13 mL/PD (IQR 6-25 mL/PD) at the non-ICU level. Consumption varied by
country and hospital type. Most ICUs (86%) had AHRs available at 76-100% of
points of care, but only approximately two-thirds (65%) of non-ICUs did. The
availability of wall-mounted and bed-mounted AHR dispensers was significantly
associated with AHR consumption in both ICUs and non-ICUs. The data show that
further improvement in hand hygiene behaviour is needed in Europe. To what extent
factors at the national, hospital and ward levels influence AHR consumption must
be explored further.
PMID- 26417852
TI - Association between activities related to routes of infection and clinical
manifestations of melioidosis.
AB - We sought associations between route of infection by Burkholderia pseudomallei
and clinical manifestations in 330 cases of melioidosis in northeast Thailand
using bivariate multivariable logistic regression models. Activities related to
skin inoculation were negatively associated with bacteraemia, activities related
to ingestion were associated with bacteraemia, and activities related to
inhalation were associated with pneumonia. Our study suggests that route of
infection is one of the factors related to clinical manifestations of
melioidosis.
PMID- 26417853
TI - Cluster of Fusarium solani isolations in a Bronchoscopy Unit.
PMID- 26417854
TI - Pentoxifylline for intermittent claudication.
AB - BACKGROUND: Intermittent claudication (IC) is a symptom of peripheral arterial
disease (PAD) and is associated with high morbidity and mortality.
Pentoxifylline, one of many drugs used to treat IC, acts by decreasing blood
viscosity, improving erythrocyte flexibility and promoting microcirculatory flow
and tissue oxygen concentration. Many studies have evaluated the efficacy of
pentoxifylline in treating individuals with PAD, but results of these studies are
variable. This is an update of a review first published in 2012. OBJECTIVES: To
determine the efficacy of pentoxifylline in improving the walking capacity (i.e.
pain-free walking distance and total (absolute, maximum) walking distance) of
individuals with stable intermittent claudication, Fontaine stage II. SEARCH
METHODS: For this update, the Cochrane Vascular Group Trials Search Co-ordinator
searched the Specialised Register (last searched April 2015) and the Cochrane
Register of Studies (2015, Issue 3). SELECTION CRITERIA: All double-blind,
randomised controlled trials (RCTs) comparing pentoxifylline versus placebo or
any other pharmacological intervention in patients with IC Fontaine stage II.
DATA COLLECTION AND ANALYSIS: Two review authors separately assessed included
studies,. matched data and resolved disagreements by discussion. Review authors
assessed the methodological quality of studies by using the Cochrane 'Risk of
bias' tool and collected results related to pain-free walking distance (PFWD) and
total walking distance (TWD). Comparison of studies was based on duration and
dose of pentoxifylline. MAIN RESULTS: We included in this review 24 studies with
3377 participants. Seventeen studies compared pentoxifylline versus placebo. In
the seven remaining studies, pentoxifylline was compared with flunarizine (one
study), aspirin (one study), Gingko biloba extract (one study), nylidrin
hydrochloride (one study), prostaglandin E1 (two studies) and buflomedil and
nifedipine (one study). The quality of the evidence was generally low, with large
variability in reported findings.. Most included studies did not report on random
sequence generation and allocation concealment, did not provide adequate
information to allow selective reporting to be judged and did not report blinding
of assessors. Heterogeneity between included studies was considerable with
regards to multiple variables, including duration of treatment, dose of
pentoxifylline, baseline walking distance and participant characteristics;
therefore, pooled analysis was not possible.Of 17 studies comparing
pentoxifylline with placebo, 14 reported TWD and 11 reported PFWD; the difference
in percentage improvement in TWD for pentoxifylline over placebo ranged from 1.2%
to 155.9%, and in PFWD from -33.8% to 73.9%. Testing the statistical significance
of these results generally was not possible because data were insufficient. Most
included studies suggested improvement in PFWD and TWD for pentoxifylline over
placebo and other treatments, but the statistical and clinical significance of
findings from individual trials is unclear. Pentoxifylline generally was well
tolerated; the most commonly reported side effects consisted of gastrointestinal
symptoms such as nausea. AUTHORS' CONCLUSIONS: Given the generally poor quality
of published studies and the large degree of heterogeneity evident in
interventions and in results, the overall benefit of pentoxifylline for patients
with Fontaine class II intermittent claudication remains uncertain.
Pentoxifylline was shown to be generally well tolerated.Based on total available
evidence, high-quality data are currently insufficient to reveal the benefits of
pentoxifylline for intermittent claudication.
PMID- 26417855
TI - Fertility and early pregnancy outcomes after conservative treatment for cervical
intraepithelial neoplasia.
AB - BACKGROUND: Cervical intra-epithelial neoplasia (CIN) typically occurs in young
women of reproductive age. Although several studies have reported the impact that
cervical conservative treatment may have on obstetric outcomes, there is much
less evidence for fertility and early pregnancy outcomes. OBJECTIVES: To assess
the effect of cervical treatment for CIN (excisional or ablative) on fertility
and early pregnancy outcomes. SEARCH METHODS: We searched in January 2015 the
following databases: the Cochrane Gynaecological Cancer Specialised Register,
Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library,
Issue 12, 2014), MEDLINE (up to November week 3, 2014) and EMBASE (up to week 52,
2014). SELECTION CRITERIA: We included all studies reporting on fertility and
early pregnancy outcomes (less than 24 weeks of gestation) in women with a
history of CIN treatment (excisional or ablative) as compared to women that had
not received treatment. DATA COLLECTION AND ANALYSIS: Studies were classified
according to the treatment method used and the fertility or early pregnancy
endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CI) were
calculated using a random-effects model and inter-study heterogeneity was
assessed with I(2). Two review authors (MK, AM) independently assessed the
eligibility of retrieved papers and risk of bias. The two review authors then
compared their results and any disagreements were resolved by discussion. If
still unresolved, a third review author (MA) was involved until consensus was
reached. MAIN RESULTS: Fifteen studies (2,223,592 participants - 25,008 treated
and 2,198,584 untreated) that fulfilled the inclusion criteria for this review
were identified from the literature search. The meta-analysis demonstrated that
treatment for CIN did not adversely affect the chances of conception. The overall
pregnancy rate was higher for treated (43%) versus untreated women (38%; RR 1.29,
95% CI 1.02 to 1.64; 4 studies, 38,050 participants, very low quality), although
the inter-study heterogeneity was considerable (P < 0.01). The pregnancy rates in
treated and untreated women with an intention to conceive (88% versus 95%, RR
0.93, 95% CI 0.80 to 1.08; 2 studies, 70 participants, very low quality) and the
number of women requiring more than 12 months to conceive (14% versus 9%, RR
1.45, 95% CI 0.89 to 2.37; 3 studies, 1348 participants, very low quality) were
no different. Although the total miscarriage rate (4.6% versus 2.8%, RR 1.04, 95%
CI 0.90 to 1.21; 10 studies, 39,504 participants, low quality) and first
trimester miscarriage rate (9.8% versus 8.4%, RR 1.16, 95% CI 0.80 to 1.69, 4
studies, 1103 participants, low quality) was similar for treated and untreated
women, CIN treatment was associated with an increased risk of second trimester
miscarriage, (1.6% versus 0.4%, RR 2.60, 95% CI 1.45 to 4.67; 8 studies,
2,182,268 participants, low quality). The number of ectopic pregnancies (1.6%
versus 0.8%, RR 1.89, 95% CI 1.50 to 2.39; 6 studies, 38,193 participants, low
quality) and terminations (12.2% versus 7.4%, RR 1.71, 95% CI 1.31 to 2.22; 7
studies, 38,208 participants, low quality) were also higher in treated women.The
results should be interpreted with caution. The included studies were often small
with heterogenous design. Most of these studies were retrospective and of low or
very low quality (GRADE assessment) and were therefore prone to bias. Subgroup
analyses for the individual treatment methods and comparison groups and analysis
to stratify for the cone length was not possible. AUTHORS' CONCLUSIONS: This meta
analysis suggests that treatment for CIN does not adversely affect fertility,
although treatment was associated with an increased risk of miscarriage in the
second trimester. These results should be interpreted with caution as the
included studies were non-randomised and many were of low or very low quality and
therefore at high risk of bias. Research should explore mechanisms that may
explain the increase in mid-trimester miscarriage risk and stratify this impact
of treatment by the length of the cone and the treatment method used.
PMID- 26417856
TI - Clinical, cytogenetic, and molecular findings in a patient with a
46,XX,del(18)(q22)/46,XX,idic(18)(q22) karyotype.
AB - Pseudoisodicentric or asymmetrical dicentric chromosomes 18 are rare findings in
clinical cytogenetics. So far, only 8 patients with breakpoints in 18q have been
reported and in none of them breakpoints were narrowed down to the molecular
level. Here, we describe a 17 months old girl with a perimembranous ventricular
septal defect, cleft palate, and minor dysmorphism including hypertelorism, flat
nose, frontal bossing and low set ears as well as mosaicism for a cell line with
a pseudoisodicentric chromosome 18q and a second cell line with a terminal
deletion of 11 Mb in 18q22.2->qter. SNP-array investigation revealed a symmetric
breakpoint in 18q22.2 and most likely postzygotic formation from the maternal
chromosome 18. Clinical findings in all patients reported so far as well as in
the patient presented here were in part overlapping with the clinical phenotypes
of trisomy 18 and partial monosomy 18q.
PMID- 26417857
TI - Data and preprints.
PMID- 26417858
TI - Gene signatures from pancreatic cancer tumor and stromal cells predict disease
outcome.
AB - Pancreatic cancers consist of a heterogeneous amalgam of assorted cell types,
making it challenging to develop a classification system that groups these tumors
according to common molecular features. A new study tackles this important issue
using bioinformatics approaches to decipher gene expression signatures derived
specifically from either tumor cells or nonmalignant stromal cells that predict
patient outcome and may inform personalized treatments.
PMID- 26417859
TI - Adeno-associated virus finds its disease.
AB - Adeno-associated virus (AAV) vectors have been widely adopted for use in gene
therapy. A new study raises concerns regarding this approach, reporting that
chromosomal insertions of AAV serotype 2 seem to activate proto-oncogenes in
human hepatocellular carcinoma.
PMID- 26417860
TI - PRC1 proteins orchestrate three-dimensional genome architecture.
AB - The three-dimensional organization of the genome has an important role in
orchestrating gene expression, but its regulation is poorly understood. Now, a
new study uncovers a major role for Polycomb components of the PRC1 complex in
organizing physical networks of genes that are co-repressed to maintain
pluripotency.
PMID- 26417861
TI - How do emergency medicine residency core faculty obtain their ultrasound training
for credentialing?
PMID- 26417862
TI - A Quantitative Method for Microtubule Analysis in Fluorescence Images.
AB - Microtubule analysis is of significant value for a better understanding of normal
and pathological cellular processes. Although immunofluorescence microscopic
techniques have proven useful in the study of microtubules, comparative results
commonly rely on a descriptive and subjective visual analysis. We developed an
objective and quantitative method based on image processing and analysis of
fluorescently labeled microtubular patterns in cultured cells. We used a multi
parameter approach by analyzing four quantifiable characteristics to compose our
quantitative feature set. Then we interpreted specific changes in the parameters
and revealed the contribution of each feature set using principal component
analysis. In addition, we verified that different treatment groups could be
clearly discriminated using principal components of the multi-parameter model.
High predictive accuracy of four commonly used multi-classification methods
confirmed our method. These results demonstrated the effectiveness and efficiency
of our method in the analysis of microtubules in fluorescence images. Application
of the analytical methods presented here provides information concerning the
organization and modification of microtubules, and could aid in the further
understanding of structural and functional aspects of microtubules under normal
and pathological conditions.
PMID- 26417863
TI - Urodynamic findings in women with refractory overactive bladder symptoms.
AB - OBJECTIVES: To assess: (i) the correlation between overactive bladder symptoms
and urodynamic findings in female patients; and (ii) the association of urinary
symptoms with the presence of detrusor overactivity and/or bladder outlet
obstruction. METHODS: The present retrospective study included female patients
with overactive bladder symptoms who underwent urodynamic evaluation by a single
physician. Patients with previous anti-incontinence surgery or neurogenic bladder
were excluded. Spearman's correlation coefficients were calculated to correlate
overactive bladder symptoms with the urodynamic findings. Univariate and
multivariate logistic regression analyses were used to determine the independent
factors for detrusor overactivity and bladder outlet obstruction. RESULTS:
Overall, 1737 reports were analyzed. All patients had urgency with or without
urgency urinary incontinence. Urgency, urgency urinary incontinence and nocturia
correlated with detrusor overactivity. The severity of frequency, nocturia and
slow stream correlated with bladder outlet obstruction. In contrast, stress
urinary incontinence showed an inverse, but weak, correlation with bladder outlet
obstruction. Stress urinary incontinence correlated moderately with urine leak.
Storage symptoms showed an inverse, but weak, correlation with maximum
cystometric capacity. Multivariate analysis data showed that age, urgency,
urgency urinary incontinence and nocturia were independent predictors of detrusor
overactivity, whereas the severity of frequency was a predictor of bladder outlet
obstruction. CONCLUSION: As overactive bladder symptoms increase in severity,
female patients tend to have a smaller bladder capacity and a higher incidence of
detrusor overactivity. A significant number of these patients have bladder outlet
obstruction.
PMID- 26417864
TI - iTRAQ-based quantitative proteomic analysis of a toxigenic dinoflagellate
Alexandrium catenella and its non-toxic mutant.
AB - Paralytic shellfish toxins (PSTs) are a group of potent neurotoxic alkaloids
produced by cyanobacteria and dinoflagellates. The PST biosynthesis gene cluster
and several toxin-related proteins have been unveiled in cyanobacteria, yet
little is known about dinoflagellates. Here, we compared the protein profiles of
a toxin-producing dinoflagellate Alexandrium catenella (ACHK-T) and its non-toxic
mutant (ACHK-NT), and characterized differentially displayed proteins using a
combination of the iTRAQ-based proteomic approach and the transcriptomic
database. Totally 3488 proteins were identified from A. catenella, and proteins
involved in carbohydrate, amino acid and energy metabolism were the most
abundant. Among them, 185 proteins were differentially displayed: proteins
involved in amino acid biosynthesis, protein and carbohydrate metabolism and
bioluminescence were more abundant in ACHK-T, while proteins participating in
photosynthesis, fatty acid biosynthesis, and the processes occurring in
peroxisome displayed higher abundances in ACHK-NT. Seven toxin-related proteins
were identified but they varied insignificantly between the two strains.
Different carbon and energy utilization strategies were potentially related to
the toxin producing ability, and the regulation mechanism of PST biosynthesis was
more complex in dinoflagellates. Our study provides the first comprehensive
dataset on the dinoflagellate proteome and lays the groundwork for future
proteomic study.
PMID- 26417865
TI - The role of the pubococcygeus muscle in the urethrogenital reflex of male rats.
AB - AIM: To determine the response of the pubococcygeus muscle (Pcm) during the
urethrogenital reflex (UGR). METHODS: Urethane-anesthetized male rats (n = 20)
were used to describe the gross anatomy of the Pcm (n = 3), the effect of the
electrical stimulation of the Pcm on the urethral pressure (n = 3), and the
reflex activity of the Pcm due to the mechanical stimulation of the urethra (n =
3) and during penile and urethrogenital reflexes (n = 11). The urethral pressure
(UP) was recorded as a response to penile stimulation (brushing, extension, and
occlusion) and during the UGR; the electromyographic activity of the Pcm was
simultaneously evaluated. The role of the Pcm was assessed by measuring urethral
pressure variables before and after denervation of this muscle. RESULTS: The Pcm
is innervated by the caudal branch of the somatomotor branch of the pelvic nerve.
The electrically induced contraction of the Pcm increased the UP. The mechanical
stimulation of the urethra during the induced micturition caused the reflex
activity of the Pcm. The different penile stimuli caused bursts of activity of
the Pcm. During the UGR, the Pcm exhibited a tonic activity. The transection of
the caudal branch of the Smb reduced the maximal UP during the penile
stimulation. The same was true regarding the duration of the UGR, the pressure
that triggers the UGR, and the highest pressure observed during the UGR.
CONCLUSION: Our results suggest that the activation of the Pcm is relevant for
the UGR in male rats. Neurourol. Urodynam. 36:80-85, 2017. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26417866
TI - Selection of voxel size and photon number in voxel-based Monte Carlo method:
criteria and applications.
AB - The voxel-based Monte Carlo method (VMC) is now a gold standard in the simulation
of light propagation in turbid media. For complex tissue structures, however, the
computational cost will be higher when small voxels are used to improve
smoothness of tissue interface and a large number of photons are used to obtain
accurate results. To reduce computational cost, criteria were proposed to
determine the voxel size and photon number in 3-dimensional VMC simulations with
acceptable accuracy and computation time. The selection of the voxel size can be
expressed as a function of tissue geometry and optical properties. The photon
number should be at least 5 times the total voxel number. These criteria are
further applied in developing a photon ray splitting scheme of local grid
refinement technique to reduce computational cost of a nonuniform tissue
structure with significantly varying optical properties. In the proposed
technique, a nonuniform refined grid system is used, where fine grids are used
for the tissue with high absorption and complex geometry, and coarse grids are
used for the other part. In this technique, the total photon number is selected
based on the voxel size of the coarse grid. Furthermore, the photon-splitting
scheme is developed to satisfy the statistical accuracy requirement for the dense
grid area. Result shows that local grid refinement technique photon ray splitting
scheme can accelerate the computation by 7.6 times (reduce time consumption from
17.5 to 2.3 h) in the simulation of laser light energy deposition in skin tissue
that contains port wine stain lesions.
PMID- 26417867
TI - Early Repolarization Pattern: Another Brick in the Wall of Vagal Tone.
PMID- 26417868
TI - Relationship between J Waves and Vagal Activity in Patients Who Do Not Have
Structural Heart Disease.
AB - BACKGROUND: J waves are associated with increased vagal activity in patients with
idiopathic ventricular fibrillation in several studies to date. However, the
relationship between J waves and autonomic nervous activity in patients without
structural heart disease remains under investigation. We investigated whether the
presence of a J wave on the surface electrocardiogram (ECG) was related to
increased vagal activity in patients without structural heart disease. METHODS:
This retrospective study included 684 patients without structural heart disease
who had undergone Holter ECG and surface ECG monitoring. Based on the presence of
J waves on the surface ECG, patients were divided into two groups: those with J
waves (group 1) and those without J waves (group 2). We compared heart rate
variability (HRV), reflecting autonomic nervous activity, using 24-h Holter ECG
between the groups. RESULTS: J waves were present in 92 (13.4%) patients. Heart
rate (HR) in group 1 was significantly lesser than that in group 2 (P = 0.031).
The ratio of low-frequency (LF) components to high-frequency (HF) components
(LF/HF) in group 1 was significantly lower than that in group 2 (P = 0.001). The
square root of the mean squared differences of successive NN intervals in group 1
was also significantly higher than that in group 2 (P = 0.047). In a multivariate
regression analysis, male sex, HR, and LF/HF ratio remained independent
determinants for the presence of J waves (P = 0.039, P = 0.036, and P < 0.001,
respectively). CONCLUSION: In patients without structural heart disease, the
presence of a J wave was associated with a slow HR, male sex, and increased vagal
activity, independently.
PMID- 26417869
TI - Isolated Left Ventricular Apical Hypoplasia with Right Ventricular Outflow Tract
Obstruction: A Rare Combination.
AB - Isolated left ventricular (LV) apical hypoplasia is a unusual and recently
recognized congenital cardiac anomaly. A 19-year-old man was found to have an
abnormal ECG and cardiac murmur identified during a routine health check since
joining work. His ECG revealed normal sinus rhythm, right-axis deviation, poor R
wave progression, and T wave abnormalities. On physical examination, a 2/6~3/6
systolic murmur was heard at the second intercostal space along the left sternal
border. Subsequent echocardiography and cardiac magnetic resonance imaging
confirmed the LV apical hypoplasia. Of note, we first found that LV apical
hypoplasia was accompanied by RV outflow tract obstruction due to exaggerated
rightward bulging of the basal-anterior septum during systole. A close follow-up
was performed for the development of heart failure, pulmonary hypertension, and
potentially tachyarrhythmia.
PMID- 26417871
TI - Striving for optimal care: Updates in quality, value, and patient experience.
AB - BACKGROUND: Hospitalists are playing a growing role in quality improvement
efforts, and they are increasingly spearheading programs to improve patient
experience and healthcare value. We aimed to summarize and critique recent
research related to quality, value, and patient experience in the clinical
practice of hospital medicine. METHODS: We reviewed articles published between
January 2014 and February 2015, identified through a hand search of leading
journals, continuing medical education collaborative journal reviews, Agency for
Healthcare Research and Quality's Patient Safety network, and PubMed. The authors
collectively selected 9 articles based on their relevance to hospital practice.
We review their findings, strengths, and limitations and make recommendations for
practice. This is a summary of an update we presented at the 2015 Hospital
Medicine national meeting. RESULTS: Key findings include: a comprehensive hand
off program was associated with improved patient safety; successful readmissions
interventions were resource-intensive, multifaceted and increased patient
capacity to handle illness; patient activation was correlated with lower resource
use post-hospitalization; positive associations exist between patient experience
and understanding of their hospitalization; hospitals and practitioners can adopt
simple low-cost strategies to reduce the trauma of hospitalization; hospitalists
frequently order low-value tests, most often to reassure themselves or their
patients; broad-spectrum antibiotics are grossly overused in hospitalized
patients leading to preventable harms including clostridium difficile colitis,
and programs that support "self-stewardship" may help moderate this risk.
CONCLUSIONS: Recent research provides important insights into readmissions
prevention, patient experience and low-value test ordering, as well as introduces
interventions that may mitigate the risks of handoffs and the overuse of broad
spectrum antibiotics.
PMID- 26417872
TI - Solution and air stable host/guest architectures from a single layer covalent
organic framework.
AB - We show that the surface-supported two-dimensional covalent organic framework
(COF) known as COF-1 can act as a host architecture for C60 fullerene molecules,
predictably trapping the molecules under a range of conditions. The fullerenes
occupy the COF-1 lattice at the solution/solid interface, and in dried films of
the COF-1/fullerene network that can be synthesized through either drop
deposition of fullerene solution or by a dipstick-type synthesis in which the
surface-supported COF-1 is briefly dipped into the fullerene solution.
PMID- 26417870
TI - Potential causal associations between vitamin D and uric acid: Bidirectional
mediation analysis.
AB - Vitamin D deficiency, a major public-health worldwide, is associated with
hyperuricemia but casual association is questioned. The study was conducted to
determine potential causal associations between 25-hydroxy vitamin D (25(OH)D)
and uric acid (UA). A cross-sectional study of the Electricity Generating
Authority of Thailand (EGAT3) cohort was conducted. Subjects (n = 2,288) were
used to genotype the group-specific component (GC) at rs2282679 and ATP-binding
cassette subfamily G member 2 (ABCG2) at rs2231142. Mediation analysis with 1000
replication bootstrap was applied to construct causal pathways i.e., rs2282679 ->
25(OH)D -> UA and rs2231142 -> UA -> 25(OH)D: The mediator (i.e., 25(OH)D and UA)
was firstly regressed on the studied gene (i.e., rs2282679 and rs2231142). A
potential causal effect of C allele on UA through 25(OH)D was -0.0236 (95% CI:
0.0411, -0.0058), indicating every minor C allele resulted in decreasing the
25(OH)D and then significantly decreased the UA by 0.0236 unit. For the second
pathway, the mediation effect was 0.0806 (95% CI: 0.0107, 0.1628); every T allele
copy for rs2231142 increased UA and thus increased 25(OH)D by 0.0806 unit. Our
study suggested potential causal associations between the GC gene and UA through
the 25(OH)D mediator, and the ABCG2 and the 25(OH)D through the UA mediator but
the absolute effects are very clinically small.
PMID- 26417873
TI - Obituary--D. Gentry Steele (1941-2014).
PMID- 26417874
TI - Rhodium(III)-Catalyzed Directed ortho-C-H Bond Functionalization of Aromatic
Ketazines via C-S and C-C Coupling.
AB - Described herein is a convenient and efficient method for sulfuration and
olefination of aromatic ketazines via rhodium-catalyzed oxidative C-H bond
activation. A range of substituted substrates are supported, and a possible
mechanism is proposed according to experimental results of kinetic isotopic
effect, reversibility studies, and catalysis of rhodacycle intermediate c1.
PMID- 26417875
TI - Exploration of high-density protein microarrays for antibody validation and
autoimmunity profiling.
AB - High-density protein microarrays of recombinant human protein fragments,
representing 12,412 unique Ensembl Gene IDs, have here been produced and
explored. These protein microarrays were used to analyse antibody off-target
interactions, as well as for profiling the human autoantibody repertoire in
plasma against the antigens represented by the protein fragments. Affinity
purified polyclonal antibodies produced within the Human Protein Atlas (HPA) were
analysed on microarrays of three different sizes, ranging from 384 antigens to
21,120 antigens, for evaluation of the antibody validation criteria in the HPA.
Plasma samples from secondary progressive multiple sclerosis patients were also
screened in order to explore the feasibility of these arrays for broad-scale
profiling of autoantibody reactivity. Furthermore, analysis on these near
proteome-wide microarrays was complemented with analysis on HuProtTM Human
Proteome protein microarrays. The HPA recombinant protein microarray with 21,120
antigens and the HuProtTM Human Proteome protein microarray are currently the
largest protein microarray platforms available to date. The results on these
arrays show that the Human Protein Atlas antibodies have few off-target
interactions if the antibody validation criteria are kept stringent and
demonstrate that the HPA-produced high-density recombinant protein fragment
microarrays allow for a high-throughput analysis of plasma for identification of
possible autoantibody targets in the context of various autoimmune conditions.
PMID- 26417876
TI - Risk Factors for Chronic Renal Insufficiency Following Cardiac Transplantation.
AB - Although previous publications have discussed kidney disease in nonrenal solid
organ transplantation, none has reviewed thoroughly the potential predictors of
long-term renal impairment in cardiac recipients. Thus, the purpose of this
review article is to summarize the current state of knowledge on risk factors of
chronic renal insufficiency in heart transplant patients. An English language
Medline literature search (1946-April 2014) was conducted using the search terms
renal insufficiency, kidney failure, kidney diseases, nephrotoxi$ ($ for
truncation), creatinine, glomerular filtration rate, heart transplantation and
organ transplantation. Additional references were identified from a review of
literature citations. A total of 74 articles discussing key risk factors were
included in the manuscript. The existing literature reveals that several
recipient characteristics (age, female sex, pretransplant/early post-transplant
kidney impairment, diabetes, and hypertension) increase the risk of renal
insufficiency after transplantation. Current data also indicate that, while
cyclosporine and tacrolimus are most likely major determinants of post-transplant
kidney failure, the effects of calcineurin inhibitor doses and concentrations
remain unclear. A small number of studies suggest that tacrolimus could possibly
induce less nephrotoxicity than cyclosporine, but meta-analyses of randomized
controlled trials show the opposite with comparable incidences of dialysis after
cardiac transplantation. Finally, the role of genetic variations has only been
explored to a limited extent in heart transplant patients. This growing body of
evidence should ultimately lead to a better risk prediction regarding chronic
renal insufficiency following cardiac transplantation and a more personalized
tailoring of immunosuppressive regimens.
PMID- 26417877
TI - Differences in the seasonality of Middle East respiratory syndrome coronavirus
and influenza in the Middle East.
PMID- 26417878
TI - Interim estimates of divergence date and vaccine strain match of human influenza
A(H3N2) virus from systematic influenza surveillance (2010-2015) in Hangzhou,
southeast of China.
AB - OBJECTIVES: In the post-pandemic period 2010-2015, seasonal influenza A(H3N2)
virus predominated in Hangzhou, southeast of China, with an increased activity
and semi-annual seasons. This study utilized HA virus gene segment sequences to
analyze the divergence date and vaccine strain match of human influenza A(H3N2)
virus from systematic influenza surveillance in Hangzhou. METHODS: Virological
and serological analyses of 124 representative A(H3N2) viruses from prospective
studies of systematic surveillance samples were conducted to quantify the genetic
and antigenic characteristics and their vaccine strain match. RESULTS: Bayesian
phylogenetic inference showed that two separate subgroups 3C.3 and 3C.2 probably
diverged from group 3C in early 2012 and then evolved into groups 3C.3a and
3C.2a, respectively, in the 2014/15 influenza season. Furthermore, high amino
acid substitution rates of the HA1 subunit were found in A(H3N2) group 3C.2a
variants, indicating that increased antigenic drift of A(H3N2) group 3C.2a virus
is associated with a vaccine mismatch to the 2015/16 vaccine reference strain
Switzerland/9715293/2013 (group 3C.3a). CONCLUSIONS: A portion of the group 3C.2a
isolates are not covered by the current A(H3N2) vaccine strain. These findings
offer insights into the emergence of group 3C.2a variants with epidemic potential
in the imminent influenza seasons.
PMID- 26417879
TI - Comparative proteomics of Shigella flexneri 2a strain 301 using a rabbit ileal
loop model reveals key proteins for bacterial adaptation in host niches.
AB - OBJECTIVES: Many studies focusing on changes in the host following Shigella spp
invasion have been reported in recent years. However, the key factors required
for the adaptation of these pathogens to host niches have usually been neglected.
METHODS: In this study, a comparative proteomic analysis was performed to examine
changes in the protein expression profile of Shigella flexneri within the host
using a rabbit ileal loop model to reveal proteins that are associated with
pathogenic adaptation. RESULTS: The protein expression profiles of bacteria
isolated from the ileum and colon were very similar, although they differed
slightly from that of bacteria isolated from the cecum. When compared with the
sample in vitro, the expressions of seven proteins were found to be upshifted in
vivo (OmpA, YgiW, MglB, YfiD, MetK, TktA, and AhpF), while two proteins were down
regulated (ElaB and GlnH). CONCLUSIONS: The abundance of nine proteins changed in
vivo, suggesting that these proteins may contribute to adaptation to the
intestinal lumen.
PMID- 26417880
TI - The epidemiology of hepatitis C virus in Afghanistan: systematic review and meta
analysis.
AB - OBJECTIVES: To characterize hepatitis C virus (HCV) epidemiology and inform
public health research, policy, and programming priorities in Afghanistan.
METHODS: Records of HCV incidence and prevalence were reviewed systematically and
synthesized following PRISMA guidelines. Meta-analyses were implemented using a
DerSimonian-Laird random effects model with inverse variance weighting to
estimate HCV prevalence among various at risk populations. A risk of bias
assessment was incorporated. RESULTS: The search identified one HCV incidence and
76 HCV prevalence measures. HCV incidence was only assessed among people who
inject drugs (PWID), and was reported at 66.7 per 100 person-years. Meta-analyses
estimated HCV prevalence at 0.7% among the general population (range 0-9.1%, 95%
confidence interval (CI) 0.5-0.9%), 32.6% among PWID (range 9.5-70.0%, 95% CI
24.5-41.3%), and 2.3% among populations at intermediate risk (range 0.0-8.3%, 95%
CI 1.3-3.7%). No data were available for other high risk populations such as
hemodialysis, thalassemia, and hemophilia patients. CONCLUSIONS: HCV prevalence
among the general population in Afghanistan is comparable to global levels. Data
are needed for the level of infection among key clinical populations at high risk
of infection. There is also an immediate need for expansion of harm reduction
programs among PWID and prisoners.
PMID- 26417881
TI - Metabolite profiling reveals temperature effects on the VOCs and flavonoids of
different plant populations.
AB - Temperature is one of the key factors in limiting the distribution of plants and
controlling major metabolic processes. A series of simulated reciprocal
transplant experiments were performed to investigate the effect of temperature on
plant chemical composition. Polygonum minus of different lowland and highland
origin were grown under a controlled environment with different temperature
regimes to study the effects on secondary metabolites. We applied gas
chromatography-mass spectrometry and liquid chromatography time-of-flight mass
spectrometry to identify the chemical compounds. A total of 37 volatile organic
compounds and 85 flavonoids were detected, with the largest response observed in
the compositional changes of aldehydes and terpenes in highland plants under
higher temperature treatment. Significantly less anthocyanidin compounds and
larger amounts of flavonols were detected under higher temperature treatment. We
also studied natural variation in the different plant populations growing under
the same environment and identified compounds unique to each population through
metabolite fingerprinting. This study shows that the origin of different plant
populations influences the effects of temperature on chemical composition.
PMID- 26417882
TI - An UPLC-MS detection method for the quantification of five antibiotics in human
plasma.
AB - BACKGROUND: An UPLC-MS detection method for the quantification of amikacin,
flucloxacillin, meropenem, penicillin G and vancomycin was developed and
validated. RESULTS: The calibration curves were found to be linear from 0.47 to
50 mg/l for amikacin, 1.28 to 135 mg/l for flucloxacillin, 0.75 to 80 mg/l for
meropenem, 0.38 to 80 mg/l for penicillin G and 0.73 to 80 mg/l for vancomycin.
Between- and within-run accuracy was ranged between 85 and 115%. Between and
within imprecision expressed as CV was within 15%. CONCLUSION: The validated
method was successfully applied to a PK study in very preterm and small for
gestational age infants treated for nosocomial sepsis and/or meningitis.
PMID- 26417883
TI - Protease activity of Per a 10 potentiates Th2 polarization by increasing IL-23
and OX40L.
AB - Proteases are implicated in exacerbation of allergic diseases. In this study, the
role of proteolytic activity of Per a 10 was evaluated on Th2 polarization.
Intranasal administration of Per a 10 in mice led to allergic airway inflammation
as seen by higher IgE levels, cellular infiltration, IL-17A, and Th2 cytokines,
whereas, inactive (Delta)Per a 10 showed attenuated response. There was an
increased OX40L expression on lung and lymph node dendritic cells in Per a 10
immunized group and on Per a 10 stimulated BMDCs. Reduction in CD40 expression
without any change at transcript level in lungs of Per a 10 immunized mice
suggested CD40 cleavage. BMDCs pulsed with Per a 10 showed reduced CD40
expression with lower IL-12p70 secretion as compared to heat inactivated Per a
10. IL-23, TNF-alpha, and IL-6 levels were significantly higher in Per a 10
stimulated BMDCs supernatant. In DC-T cell coculture studies, Per a 10 pulsed
BMDCs showed higher levels of IL-4 and IL-13 that were reduced on blocking of
either IL-23 or OX40L. In conclusion, the data suggests a critical role of
protease activity of Per a 10 in promoting Th2 polarization by increasing IL-23
secretion and OX40L expression on dendritic cells.
PMID- 26417884
TI - Predictive factors of adverse events after intravesical suburothelial
onabotulinumtoxina injections for overactive bladder syndrome-A real-life
practice of 290 cases in a single center.
AB - AIMS: Patients often experience adverse events (AEs) after intravesical
onabotulinumtoxinA (BoNT-A) treatment for overactive bladder refractory to
antimuscarinic agents. We investigated the prevalence and predictive factors of
AEs in such patients. METHODS: A total of 290 patients underwent intravesical
BoNT-A (100 U) suburothelial injection. The age, gender, overactive bladder
subtypes, medical co-morbidities, and neurological diseases of the patients were
recorded. The maximum flow rate (Qmax ), voided volume, post-void residual (PVR)
volume, and voiding efficiency (VE) at baseline were analyzed to identify adverse
events within 3 months after treatment. RESULTS: Acute urinary retention (AUR)
developed in 24 patients (8.3%), and urinary tract infection (UTI) occurred in 44
(15.2%) within 3 months of treatment. Large PVR volume (>200 ml) occurred in 81
(27.9%), 68 (24.3%), and 49 (18.4%) patients 1, 3, and 6 months after treatment,
respectively. AUR developed significantly more often in men, patients >61 years
old, those with a baseline Qmax <=15 ml/sec, PVR >=100 ml, and VE <90%. Patients
older than 61 years had a higher incidence of large PVR 1 month after treatment.
Female gender and a baseline PVR volume >=100 ml had a greater incidence of UTI.
Age >61 years, low Qmax , low voiding efficiency, and large PVR at baseline were
also risk factors for adverse events. CONCLUSION: AUR, UTI, and large PVR volume
are common AEs after BoNT-A treatment. Patients with overactive bladders that are
at risk of developing AEs after BoNT-A injection should be informed of the
possible AEs. Neurourol. Urodynam. 36:142-147, 2017. (c) 2015 Wiley Periodicals,
Inc.
PMID- 26417885
TI - Placebo and nocebo effects on itch: effects, mechanisms, and predictors.
AB - Placebo and nocebo effects have been extensively studied in the field of pain and
more recently also on itch. In accordance with placebo research on pain,
expectancy learning via verbal suggestion or conditioning has shown to induce
placebo and nocebo effects on itch, in which the combination of both procedures
seems most promising. Moreover, itch can also be transferred 'contagiously' in
which suggestion and social behavioural learning seem to play a role. With regard
to predictors of placebo and nocebo responding on itch and contagious itch,
preliminary evidence suggests a role for individual psychological characteristics
and personality traits regarding negative outcome expectancies. Although findings
on placebo and nocebo effects on itch seem comparable to pain, we have only just
begun to understand the underlying mechanisms and predictors of placebo and
nocebo effects on itch.
PMID- 26417886
TI - Unified Protocol for Cobalt-Catalyzed Oxidative Assembly of Two Aryl Metal
Reagents Using Oxygen as an Oxidant.
AB - The first cobalt-catalyzed oxidative cross-coupling reaction of two aryl metal
reagents is described. An equivalent amount of two aryl Grignard or lithium
reagents, after mediation by an equivalent amount of simple ClTi(OEt)3, was
facilely assembled under the catalysis of 1 mol % of CoCl2/10 mol % of DMPU using
oxygen. The cross-couplings between various aryl metal reagents, especially
between two structurally similar aryl Grignard reagents, proceeded smoothly and
selectively and, thus, provided a highly general and efficient method for the
construction of biaryl compounds.
PMID- 26417887
TI - Selective recognition and extraction of KBr via cooperative interactions with a
urea functionalized crown ether dual-host.
AB - Selective solid-liquid extraction of KBr is demonstrated for the first time with
a crown ether based pentafluorophenyl urea functionalized dual-host receptor.
(1)H-NMR and ITC studies have been carried out to illustrate the effect of
cooperativity towards the recognition of alkali metal salts.
PMID- 26417889
TI - From Pakistan a line of hope for 'The Polio Eradication and Endgame Strategic
Plan 2013-2018'.
PMID- 26417890
TI - Magnetically-induced ferroelectricity in the (ND4)2[FeCl5(D2O)] molecular
compound.
AB - The number of magnetoelectric multiferroic materials reported to date is scarce,
as magnetic structures that break inversion symmetry and induce an improper
ferroelectric polarization typically arise through subtle competition between
different magnetic interactions. The (NH4)2[FeCl5(H2O)] compound is a rare case
where such improper ferroelectricity has been observed in a molecular material.
We have used single crystal and powder neutron diffraction to obtain detailed
solutions for the crystal and magnetic structures of (NH4)2[FeCl5(H2O)], from
which we determined the mechanism of multiferroicity. From the crystal structure
analysis, we observed an order-disorder phase transition related to the ordering
of the ammonium counterion. We have determined the magnetic structure below TN,
at 2 K and zero magnetic field, which corresponds to a cycloidal spin arrangement
with magnetic moments contained in the ac-plane, propagating parallel to the c
axis. The observed ferroelectricity can be explained, from the obtained magnetic
structure, via the inverse Dzyaloshinskii-Moriya mechanism.
PMID- 26417891
TI - Multivalent presentation of carbohydrates by 3(14)-helical peptide templates:
synthesis, conformational analysis using CD spectroscopy and saccharide
recognition.
AB - A well defined 314-helical tetravalent beta-galactopeptide site-specific
functionalised template (SSFT) 1 was prepared containing d-galactose units, with
free anomeric carbons as the aldehyde tags, and was explored via ligation with
different aminoxy sugars (alpha-/beta-d-glucose, alpha/beta-d-galactose, alpha-d
mannose and beta-d-lactose) to get 314-helical carbohydrate-functionalised
multivalent glycoconjugates 2-7. Preliminary recognition studies of tetramannosyl
glycoconjugate 4 with a specific lectin (concanavalin A) using fluorescence
anisotropy showed an increase in binding affinity and the multivalency effect was
found to be increased by 6.5 times per glycan.
PMID- 26417892
TI - Peri-operative management of the surgical patient with diabetes 2015: Association
of Anaesthetists of Great Britain and Ireland.
AB - Diabetes affects 10-15% of the surgical population and patients with diabetes
undergoing surgery have greater complication rates, mortality rates and length of
hospital stay. Modern management of the surgical patient with diabetes focuses
on: thorough pre-operative assessment and optimisation of their diabetes (as
defined by a HbA1c < 69 mmol.mol(-1) ); deciding if the patient can be managed by
simple manipulation of pre-existing treatment during a short starvation period
(maximum of one missed meal) rather than use of a variable-rate intravenous
insulin infusion; and safe use of the latter when it is the only option, for
example in emergency patients, patients expected not to return to a normal diet
immediately postoperatively, and patients with poorly controlled diabetes. In
addition, it is imperative that communication amongst healthcare professionals
and between them and the patient is accurate and well informed at all times. Most
patients with diabetes have many years of experience of managing their own care.
The purpose of this guideline is to provide detailed guidance on the peri
operative management of the surgical patient with diabetes that is specific to
anaesthetists and to ensure that all current national guidance is concordant.
PMID- 26417893
TI - The atomic and electronic structure of nitrogen- and boron-doped phosphorene.
AB - First principles modeling of nitrogen- and boron-doped phosphorene demonstrates
the tendency toward the formation of highly ordered structures. Nitrogen doping
leads to the formation of -N-P-P-P-N- lines. Further transformation into -P-N-P-N
lines across the chains of phosphorene occurs with increasing band gap and
increasing nitrogen concentration, which coincides with the decreasing chemical
activity of N-doped phosphorene. In contrast to the case of nitrogen, boron atoms
prefer to form -B-B- pairs with the further formation of -P-P-B-B-P-P- patterns
along the phosphorene chains. The low concentration of boron dopants converts the
phosphorene from a semiconductor into a semimetal with the simultaneous
enhancement of its chemical activity. Co-doping of phosphorene by both boron and
nitrogen starts from the formation of -B-N- pairs, which provides flat bands and
further transformation of these pairs into hexagonal BN lines and ribbons across
the phosphorene chains.
PMID- 26417888
TI - Brain size and limits to adult neurogenesis.
AB - The walls of the cerebral ventricles in the developing embryo harbor the primary
neural stem cells from which most neurons and glia derive. In many vertebrates,
neurogenesis continues postnatally and into adulthood in this region. Adult
neurogenesis at the ventricle has been most extensively studied in organisms with
small brains, such as reptiles, birds, and rodents. In reptiles and birds, these
progenitor cells give rise to young neurons that migrate into many regions of the
forebrain. Neurogenesis in adult rodents is also relatively widespread along the
lateral ventricles, but migration is largely restricted to the rostral migratory
stream into the olfactory bulb. Recent work indicates that the wall of the
lateral ventricle is highly regionalized, with progenitor cells giving rise to
different types of neurons depending on their location. In species with larger
brains, young neurons born in these spatially specified domains become
dramatically separated from potential final destinations. Here we hypothesize
that the increase in size and topographical complexity (e.g., intervening white
matter tracts) in larger brains may severely limit the long-term contribution of
new neurons born close to, or in, the ventricular wall. We compare the process of
adult neuronal birth, migration, and integration across species with different
brain sizes, and discuss how early regional specification of progenitor cells may
interact with brain size and affect where and when new neurons are added.
PMID- 26417894
TI - Evaluation of fatty acids in pregnancy: plasma or erythrocyte membrane?
PMID- 26417895
TI - The controversy of infant formula: does it have a role in managing child
malnutrition in fully weaned infants?
PMID- 26417897
TI - Erratum.
PMID- 26417896
TI - Response to the letter by Gedela.
PMID- 26417898
TI - Quality of online information to support patient decision-making in breast cancer
surgery.
AB - BACKGROUND: Breast cancer patients commonly use the internet as an information
resource. Our objective was to evaluate the quality of online information
available to support patients facing a decision for breast surgery. METHODS:
Breast cancer surgery-related queries were performed (Google and Bing), and
reviewed for content pertinent to breast cancer surgery. The DISCERN instrument
was used to evaluate websites' structural components that influence publication
reliability and ability of information to support treatment decision-making.
Scores of 4/5 were considered "good." RESULTS: 45 unique websites were
identified. Websites satisfied a median 5/9 content questions. Commonly omitted
topics included: having a choice between breast conservation and mastectomy (67%)
and potential for 2nd surgery to obtain negative margins after breast
conservation (60%). Websites had a median DISCERN score of 2.9 (range 2.0-4.5).
Websites achieved higher scores on structural criteria (median 3.6 [2.1-4.7]),
with 24% rated as "good." Scores on supporting decision-making questions were
lower (2.6 [1.3-4.4]), with only 7% scoring "good." CONCLUSION: Although numerous
breast cancer-related websites exist, most do a poor job providing women with
essential information necessary to actively participate in decision-making for
breast cancer surgery. Providing easily- accessible, high-quality online
information has the potential to significantly improve patients' experiences with
decision-making.
PMID- 26417899
TI - Serum Soluble Semaphorin 4D is Associated with Left Atrial Diameter in Patients
with Atrial Fibrillation.
AB - BACKGROUND: The aim of this study was to evaluate the serum soluble semaphorin 4D
(sSema4D) in patients with atrial fibrillation and to investigate the
relationship of serum sSema4D with left atrial diameter (LAD). MATERIAL AND
METHODS: We studied a total of 113 patients who were subdivided into paroxysmal
and non-paroxysmal (included persistent and permanent) atrial fibrillation
groups, respectively. Another 55 subjects without atrial fibrillation were
enrolled as the healthy control group. Serum levels of soluble semaphorin 4D
(Sema4D) were measured in all subjects using the enzyme-labeled immunosorbent
assay method. We also evaluated the coagulation parameters and left atrial
diameters. RESULTS: Patients with paroxysmal and non-paroxysmal atrial
fibrillation had significantly higher sSema4D level compared with controls
(8.50+/-2.19 ng/mL and 9.30+/-2.28 ng/mL vs. 6.56+/-1.27 ng/ml, P<0.05). Serum
sSema4D concentrations were elevated in patients with non-paroxysmal atrial
fibrillation compared to those with paroxysmal atrial fibrillation (P<0.001). The
level of sSema4D was positively correlated with LAD (r=0.606, P<0.001).
Multivariate logistic regression analysis revealed that serum sSema4D, LAD, male
sex, heart rate, hypertension, and coronary artery disease were associated with
atrial fibrillation (P<0.05). CONCLUSIONS: Serum sSema4D levels are increased in
patients with atrial fibrillation and are independently associated with atrial
remodeling.
PMID- 26417900
TI - The discovery of Antarctic RNA viruses: a new game changer.
AB - Antarctic ecosystems are dominated by micro-organisms, and viruses play
particularly important roles in the food webs. Since the first report in 2009
(Lopez-Bueno et al. ), 'omic'-based studies have greatly enlightened our
understanding of Antarctic aquatic microbial diversity and ecosystem function
(Wilkins et al. ; Cavicchioli ). This has included the discovery of many new
eukaryotic viruses (Lopez-Bueno et al. ), virophage predators of algal viruses
(Yau et al. ), bacteria with resistance to phage (Lauro et al. ) and mechanisms
of haloarchaeal evasion, defence and adaptation to viruses (Tschitschko et al. ).
In this issue of Molecular Ecology, Lopez-Bueno et al. () report the first
discovery of RNA viruses from an Antarctic aquatic environment. High sequence
coverage enabled genome variation to be assessed for four positive-sense single
stranded RNA viruses from the order Picornavirales. By examining the populations
present in the water column and in the lake's catchment area, populations of
'quasispecies' were able to be linked to local environmental factors. In view of
the importance of viruses in Antarctic ecosystems but lack of data describing
them, this study represents a significant advance in the field.
PMID- 26417902
TI - Site-Specific Antibody Labeling by Covalent Photoconjugation of Z Domains
Functionalized for Alkyne-Azide Cycloaddition Reactions.
AB - Antibodies are extensively used in research, diagnostics, and therapy, and for
many applications the antibodies need to be labeled. Labeling is typically
performed by using amine-reactive probes that target surface-exposed lysine
residues, resulting in heterogeneously labeled antibodies. An alternative
labeling strategy is based on the immunoglobulin G (IgG)-binding protein domain
Z, which binds to the Fc region of IgG. Introducing the photoactivable amino acid
benzoylphenylalanine (BPA) into the Z domain makes it possible for a covalent
bond to be be formed between the Z domain and the antibody on UV irradiation, to
produce a site-specifically labeled product. Z32 BPA was synthesized by solid
phase peptide synthesis and further functionalized to give alkyne-Z32 BPA and
azide-Z32 BPA for Cu(I) -catalyzed cycloaddition, as well as DBCO-Z32 BPA for Cu
free strain-promoted cycloaddition. The Z32 BPA variants were conjugated to the
human IgG1 antibody trastuzumab and site-specifically labeled with biotin or
fluorescein. The fluorescently labeled trastuzumab showed specific staining of
the membranes of HER2-expressing cells in immunofluorescence microscopy.
PMID- 26417901
TI - A randomized DBPC trial to determine the optimal effective and safe dose of a
SLIT-birch pollen extract for the treatment of allergic rhinitis: results of a
phase II study.
AB - BACKGROUND: Sublingual immunotherapy (SLIT) is a potential efficacious and safe
treatment option for patients with respiratory, IgE-mediated allergic diseases. A
combined tolerability, dose-finding study with a sublingual liquid birch pollen
preparation (SB) was conducted. METHODS: Two hundred and sixty-nine adults with
birch-pollen-induced AR were randomized to placebo, SB: 3333, 10,000, 20,000 or
40,000 AUN/ml. Differences in symptom scores following a titrated nasal
provocation test (TNPT) at baseline and after 5 months of treatment were
determined. Safety, tolerability, birch-pollen-specific immunoglobulin levels and
peak nasal inspiratory flow (PNIF) were also measured (all measures determined
outside the birch pollen season). RESULTS: In all treatment groups, an
improvement in symptom scores after treatment compared to baseline was observed,
with an additional stepwise improvement in the active groups compared to placebo,
which was significant in high-dose groups (P = 0.008 and P < 0.001,
respectively). For this primary endpoint, a significant linear dose-response
curve was observed: the higher the dose, the better the improvement observed.
Likewise, active treatment resulted in an increase in PNIF and serum IgG levels
compared to placebo. The highest improvements were found in the 40,000 AUN/ml
group. All active dosages resulted in more adverse reactions than placebo, which
were mainly mild and well-controlled. CONCLUSIONS: A multicentre trial evaluated
the dose-response and tolerability of SB. All active treatment groups showed
better responses than placebo for both primary and secondary parameters. The
results indicate that, within the studied dose range, SB 40,000 AUN/ml is the
most optimal effective and safe dose (ClinicalTrials.gov: NCT01639768).
PMID- 26417903
TI - Acylglycerophosphate acyltransferase 4 (AGPAT4) is a mitochondrial
lysophosphatidic acid acyltransferase that regulates brain phosphatidylcholine,
phosphatidylethanolamine, and phosphatidylinositol levels.
AB - The acylglycerophosphate acyltransferase/lysophosphatidic acid acyltransferase
(AGPAT/LPAAT) family is a group of homologous acyl-CoA-dependent lysophospholipid
acyltransferases. We performed studies to better understand the subcellular
localization, activity, and in vivo function of AGPAT4/LPAATdelta, which we found
is expressed in multiple mouse brain regions. Endogenous brain AGPAT4 and AGPAT4
overexpressed in HEK293 or Sf9 insect cells localizes to mitochondria and is
resident on the outer mitochondrial membrane. Further fractionation showed that
AGPAT4 is present specifically in the mitochondria and not in the mitochondria
associated endoplasmic reticulum membrane (i.e. MAM). Lysates from Sf9 cells
infected with baculoviral Agpat4 were tested with eight lysophospholipid species
but showed an increased activity only with lysophosphatidic acid as an acyl
acceptor. Analysis of Sf9 phospholipid species, however, indicated a significant
72% increase in phosphatidylinositol (PI) content. We examined the content of
major phospholipid species in brains of Agpat4(-/-) mice and found also a >50%
decrease in total levels of PI relative to wildtype mice, as well as significant
decreases in phosphatidylcholine (PC) and phosphatidylethanolamine (PE), but no
significant differences in phosphatidylserine, phosphatidylglycerol, cardiolipin,
or phosphatidic acid (PA). A compensatory upregulation of Agpats 1, 2, 3, 5, and
9 may help to explain the lack of difference in PA. Our findings indicate that
AGPAT4 is a mitochondrial AGPAT/LPAAT that specifically supports synthesis of
brain PI, PC, and PE. This understanding may help to explain apparent
redundancies in the AGPAT/LPAAT family.
PMID- 26417904
TI - Experienced and anticipated discrimination reported by individuals in treatment
for substance use disorders within the Netherlands.
AB - Experiences and expectations of discrimination (anticipated discrimination) may
delay treatment seeking among people with substance use disorders. In addition,
experienced and anticipated discrimination can be a barrier to successful
recovery and rehabilitation. The aim of this study was to study the level of
experienced and anticipated (the expectation to be rejected) discrimination among
individuals in treatment for substance use disorders as well as the association
between both concepts of discrimination. In addition, the association of
experienced and anticipated discrimination with clinical and social
characteristics was investigated. A cross-sectional survey among individuals in
treatment for substance use disorders in the Netherlands was carried out in 2012.
Individuals in treatment (N = 186) completed a self-reported questionnaire about
experienced and anticipated discrimination. Descriptive statistics and chi
squared analyses were performed to investigate the level of experienced and
anticipated discrimination and the association between both concepts. Linear
regression analyses were used to investigate the association with clinical and
social characteristics, such as occupational status and type of treatment.
Individuals in treatment for substance use disorders reported high levels of
experienced and anticipated discrimination. Respondents experienced most
discrimination in family ties, intimate relationships and friendships.
Experienced and anticipated discrimination were both positively correlated.
Having complex substance use problems and a longer history of substance use
problems was related to higher levels of experienced discrimination. In
conclusion, experienced and anticipated discrimination were highly prevalent
among individuals in treatment for substance use disorders. Attention in
addiction treatment for adequate coping with discrimination may be needed in
order to achieve successful social participation and rehabilitation of these
individuals.
PMID- 26417905
TI - Evaluating the Use of Twitter to Enhance the Educational Experience of a Medical
School Surgery Clerkship.
AB - OBJECTIVE: Although it has been suggested that social-networking services such as
Twitter could be used as a tool for medical education, few studies have evaluated
its use in this setting. We sought to evaluate the use of Twitter as a novel
educational tool in a medical school surgery clerkship. We hypothesized that
Twitter can enhance the educational experience of clerkship students. DESIGN: We
performed a prospective observational study. We created a new Twitter account,
and delivered approximately 3 tweets per day consisting of succinct, objective
surgical facts. Students were administered pre- and postclerkship surveys, and
aggregate test scores were obtained for participating students and historical
controls. SETTING: Required third-year medical school surgery clerkship at the
University of Michigan large tertiary-care academic hospital. PARTICIPANTS: Third
year medical students. RESULTS: The survey response rate was 94%. Preclerkship
surveys revealed that most (87%) students have smartphones, and are familiar with
Twitter (80% have used before). Following completion of the clerkship, most
students (73%) reported using the Twitter tool, and 20% used it frequently.
Overall, 59% believed it positively influenced their educational experience and
very few believed it had a negative influence (2%). However, many (53%) did not
believe it influenced their clerkship engagement. Aggregate mean National Board
of Medical Examiners Shelf Examination scores were not significantly different in
an analysis of medical student classes completing the clerkship before or after
the Twitter tool (p = 0.37). CONCLUSIONS: Most of today's learners are familiar
with social media, and own the technology necessary to implement novel
educational tools in this platform. Applications such as Twitter can be facile
educational tools to supplement and enhance the experience of students on a
medical school clerkship.
PMID- 26417906
TI - Structural and Functional Characterization of the Hazelnut Allergen Cor a 8.
AB - Nonspecific lipid transfer proteins (nsLTPs) are basic proteins, stabilized by
four disulfide bonds, and are expressed throughout the plant kingdom. These
proteins are also known as important allergens in fruits and tree nuts. In this
study, the nsLTP from hazelnuts, Cor a 8, was purified and its crystal structure
determined. The protein is stable at low pH and refolds after thermal
denaturation. Molecular dynamics simulations were used to provide an insight into
conformational changes of Cor a 8 upon ligand binding. When known epitope areas
from Pru p 3 were compared to those of Cor a 8, differences were obvious, which
may contribute to limited cross-reactivity between peach and hazelnut allergens.
Differences in epitope regions may contribute to limited cross-reactivity between
Cor a 8 and nsLTPs from other plant sources. The structure of Cor a 8 represents
the first resolved structure of a hazelnut allergen.
PMID- 26417908
TI - Heinz Lauener - Urban Folklore.
PMID- 26417907
TI - C3-induced release of neurotrophic factors from Schwann cells - potential
mechanism behind its regeneration promoting activity.
AB - Previous studies revealed a peripheral nerve regeneration (PNR)(1) promoting
activity of Clostridium botulinum C3(2) exoenzyme or a 26(mer) C-terminal peptide
fragment covering amino acids 156-181 (C3(156-181)),(3) when delivered as one
time injection at the lesion site. The current study was performed to 1)
investigate if prolonged availability of C3 and C3(156-181) at the lesion site
can further enhance PNR in vivo and to 2) elucidate effects of C3 and C3(156-181)
on Schwann cells (SCs)(4)in vitro. For in vivo studies, 10 mm adult rat sciatic
nerve gaps were reconstructed with the epineurial pouch technique or autologous
nerve grafts. Epineurial pouches were filled with a hydrogel containing i)
vehicle, ii) 40 MUM C3 or iii) 40 MUM C3(156-181). Sensory and motor functional
recovery was monitored over 12 weeks and the outcome of PNR further analyzed by
nerve morphometry. In vitro, we compared gene expression profiles (microarray
analysis) and neurotrophic factor expression (western blot analysis) of untreated
rat neonatal SCs with those treated with C3 or C3(156-181) for 72 h. Effects on
neurotrophic factor expression levels were proven in adult human SCs.
Unexpectedly, prolonged delivery of C3 and C3(156-181) at the lesion site did not
increase the outcome of PNR. Regarding the potential mechanism underlying their
previously detected PNR promoting action, however, 6 genes were found to be
commonly altered in SCs upon treatment with C3 or C3(156-181). We demonstrate
significant down-regulation of genes involved in glutamate uptake
(Eaac1,(5)Grin2a(6)) and changes in neurotrophic factor expression (increase of
FGF-2(7) and decrease of NGF(8)). Our microarray-based expression profiling
revealed novel C3-regulated genes in SCs possibly involved in the axonotrophic
(regeneration promoting) effects of C3 and C3(156-181). Detection of altered
neurotrophic factor expression by C3 or C3(156-181) treated primary neonatal rat
SCs and primary adult human SCs supports this hypothesis.
PMID- 26417909
TI - Inhibition of Neutrophil Extracellular Trap Formation after Stem Cell Transplant
by Prostaglandin E2.
AB - RATIONALE: Autologous and allogeneic hematopoietic stem cell transplant (HSCT)
patients are susceptible to pulmonary infections, including bacterial pathogens,
even after hematopoietic reconstitution. We previously reported that murine bone
marrow transplant (BMT) neutrophils overexpress cyclooxygenase-2, overproduce
prostaglandin E2 (PGE2), and exhibit defective intracellular bacterial killing.
Neutrophil extracellular traps (NETs) are DNA structures that capture and kill
extracellular bacteria and other pathogens. OBJECTIVES: To determine whether
NETosis was defective after transplant and if so, whether this was regulated by
PGE2 signaling. METHODS: Neutrophils isolated from mice and humans (both control
and HSCT subjects) were analyzed for NETosis in response to various stimuli in
the presence or absence of PGE2 signaling modifiers. MEASUREMENTS AND MAIN
RESULTS: NETs were visualized by immunofluorescence or quantified by Sytox Green
fluorescence. Treatment of BMT or HSCT neutrophils with phorbol 12-myristate 13
acetate or rapamycin resulted in reduced NET formation relative to control cells.
NET formation after BMT was rescued both in vitro and in vivo with cyclooxygenase
inhibitors. Additionally, the EP2 receptor antagonist (PF-04418948) or the EP4
antagonist (AE3-208) restored NET formation in neutrophils isolated from BMT mice
or HSCT patients. Exogenous PGE2 treatment limited NETosis of neutrophils
collected from normal human volunteers and naive mice in an exchange protein
activated by cAMP- and protein kinase A-dependent manner. CONCLUSIONS: Our
results suggest blockade of the PGE2-EP2 or EP4 signaling pathway restores
NETosis after transplantation. Furthermore, these data provide the first
description of a physiologic inhibitor of NETosis.
PMID- 26417910
TI - Incidence and Predictors of Left Ventricular Thrombus After Primary Percutaneous
Coronary Intervention for Anterior ST-Segment Elevation Myocardial Infarction.
AB - BACKGROUND: The role of warfarin in anterior ST-segment elevation myocardial
infarction (STEMI) complicated by left ventricular (LV) dysfunction in patients
treated with primary percutaneous coronary intervention (PCI) and dual
antiplatelet therapy is unclear. Warfarin may prevent cardioembolic events but
significantly increases bleeding in the setting of dual antiplatelet therapy.
HYPOTHESIS: The incidence of LV thrombus in anterior STEMI patients treated with
PCI is low, and clinical predictors might be valuable in determining patients at
risk. METHODS: We performed a retrospective, single-center study of 687
consecutive patients with anterior STEMI treated with PCI from 2006 to 2013.
Baseline variables were evaluated in 310 patients at high risk for LV thrombus
based on echocardiographic criteria. Patients with definite, probable, and no LV
thrombus were compared by ANOVA, chi(2), or t test where appropriate. Logistic
regression analysis was performed. RESULTS: The incidence of LV thrombus was 15%
(n = 47 probable/definite thrombus). Cardiac arrest was the only independent
characteristic associated with increased risk of LV thrombus (odds ratio [OR]:
4.06, 95% confidence interval [CI]: 1.3-12.7). Trends were observed for a lower
risk in cardiogenic shock (OR: 0.33, 95% CI: 0.10-1.05) and aspirin use at
baseline (OR: 0.43, 95% CI: 0.17-1.1). Treatment variables associated with LV
thrombus included unfractionated heparin use post-PCI (OR: 2.43, 95% CI: 1.16
5.1) and use of balloon angioplasty without stent. CONCLUSIONS: In contemporary
practice with primary PCI, definite LV thrombus following anterior STEMI with LV
dysfunction is challenging to predict. Further investigation is needed to
determine if there is a subset of patients that should be treated with
prophylactic warfarin.
PMID- 26417912
TI - Celecoxib enhances [sorafenib + sildenafil] lethality in cancer cells and reverts
platinum chemotherapy resistance.
AB - The present studies sought to determine whether the lethality of the drug
combination [sorafenib + sildenafil] could be enhanced by the anti-inflammatory
agent celecoxib, using ovarian cancer and other tumor cell lines as models. Also,
in a dose dependent fashion celecoxib enhanced [sorafenib + sildenafil] lethality
in multiple ovarian cancer cell lines. In a dose dependent fashion celecoxib
enhanced the ability of [sorafenib + sildenafil] to reduce expression of multiple
chaperone proteins in parallel with lower levels of the drug efflux pumps ABCB1
and ABCG2. Over-expression of GRP78 and HSP27 maintained pump expression in the
presence of drugs. Cell killing by the 3 drug combination was mediated by
mitochondrial / caspase 9 -dependent apoptotic signaling and by RIP-1 / caspases
2 and 4 / AIF -dependent necroptotic signaling. Pre-treatment of intrinsically
resistant primary ovarian cancer cells with [celecoxib + sorafenib + sildenafil]
significantly enhanced tumor cell killing by a subsequent cisplatin exposure.
Similar data were obtained in some cancer cell lines, but not all, using the
related platinum containing drugs, oxaliplatin and carboplatin. As our prior
publications have also validated in vivo the combinations of [celecoxib +
sildenafil] and [sorafenib + sildenafil] as cytotoxic to multiple tumor cell
types, combined with the present findings, we would argue that the combination of
celecoxib/sorafenib/sildenafil should be explored in a new phase I trial in
ovarian cancer.
PMID- 26417911
TI - Gd3+-1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic-2-hydroxypropyl-beta
cyclodextrin/Pluronic Polyrotaxane as a Long Circulating High Relaxivity MRI
Contrast Agent.
AB - A multivalent magnetic resonance imaging agent based on a 2-hydroxypropyl-beta
cyclodextrin (HPCD):Pluronic F127 polyrotaxane carrier has been synthesized, and
its blood pool contrast properties have been characterized. This Gd3+-DO3A
HPCD/Pluronic polyrotaxane construct is shown to circulate for more than 30 min
and provide >100-fold vascular enhancement relative to the monomeric Gd3+-DO3A
HPCD control that is rapidly cleared via the kidney. The high r1 relaxivity at 37
degrees C (23.83 mM(-1) s(-1) at 1.5 T; 34.08 mM(-1) s(-1) at 0.5 T), extended
blood circulation, well-known pharmacology of the polyrotaxane precursors, and
absence of acute toxicity make it a highly attractive blood pool contrast agent
candidate.
PMID- 26417914
TI - DNA methylation of tumor suppressor protein-coding and non-coding genes in
multiple myeloma.
AB - Multiple myeloma is an incurable hematological malignancy arising from
immortalized plasma cells in the bone marrow. DNA methylation refers to the
catalytic addition of a methyl group to the cytosine ring of a CpG dinucleotide.
Methylation of a promoter-associated CpG island, a cluster of CpG dinucleotides,
may lead to silencing of the associated gene. In carcinogenesis, methylation of
protein-coding or non-coding tumor suppressor genes/miRNAs is associated with
transcriptional silencing, loss of tumor suppressor function and prognostic
significance. This review first introduces pathogenesis of myeloma and DNA
methylation in cancer. Then, it summarizes methylation of protein-coding tumor
suppressor genes, especially, the latest genome-wide methylation studies in
myeloma, followed by the latest findings of methylation of non-coding tumor
suppressor miRNAs in myeloma.
PMID- 26417913
TI - Synergistic Efficacy from Gene Therapy with Coreceptor Blockade and a beta2
Agonist in Murine Pompe Disease.
AB - Pompe disease (glycogen storage disease type II; acid maltase deficiency) is a
devastating myopathy resulting from acid alpha-glucosidase (GAA) deficiency in
striated and smooth muscle. Despite the availability of enzyme replacement
therapy (ERT) with recombinant human GAA (rhGAA), the limitations of ERT have
prompted the preclinical development of gene therapy. Gene therapy has the
advantage of continuously producing GAA, in contrast to ERT, which requires
frequent injections of rhGAA. An adeno-associated viral (AAV) vector containing a
muscle-specific promoter, AAV-MHCK7hGAApA, achieved high GAA expression in heart
and skeletal muscle in mice with Pompe disease. However, elevated GAA activity
was not sufficient to completely clear accumulated glycogen in skeletal muscle.
The process of glycogen clearance from lysosomes might require improved
trafficking of GAA to the lysosomes in skeletal muscle, previously achieved with
the beta(2)-agonist clenbuterol that enhanced glycogen clearance in skeletal
muscle without increasing GAA activity. Glycogen clearance was clearly enhanced
by treatment with a nondepleting anti-CD4 monoclonal antibody (anti-CD4 mAb)
along with muscle-specific GAA expression in cardiac muscle, but that treatment
was not effective in skeletal muscle. Furthermore, anti-CD4 mAb treatment along
with clenbuterol achieved synergistic therapeutic efficacy in both cardiac and
skeletal muscle. This triple therapy increased both muscle strength and weight
gain. Overall, triple therapy to enhance GAA trafficking and to suppress immune
responses significantly improved the efficacy of muscle-targeted gene therapy in
murine Pompe disease.
PMID- 26417915
TI - Case Sequencing of Diagnostic Imaging Studies Performed Under General Anesthesia
or Monitored Anesthesia Care During Nights and Weekends.
AB - General anesthesia or monitored anesthesia care sometimes is provided in
nonoperating room (OR) locations during nights and weekends (e.g., for magnetic
resonance imaging [MRI] or computerized tomography [CT]). Rational and consistent
scheduling and sequencing decisions for these diagnostic imaging procedures,
including coordination with OR cases, cannot be done without knowing how long
each case can wait to be started without risking a worsening of the patient's
condition. We reviewed the medical records of the 81 patients who underwent
diagnostic imaging procedures (78 = MRI, 3 = CT scan) under general anesthesia or
monitored anesthesia care either on weekends or between 6 pm and 6 am at the
University of Iowa Hospitals between March 2012 and February 2014. For 77.8% of
patients, the indications could have changed clinical management within 4 hours
(N = 63/81). Among the 63 imaging studies with potential immediate impact, there
was documentation of results having been communicated to the treating team within
4 hours of the completion of imaging for 39 of the patients. Among the 39
patients, 15 promptly received medications or underwent procedures based on the
imaging results. Thus, 15 of the 81 patients had a change in care (18.5%, 95%
lower confidence limit = 11.2%). Our results are important since we showed
previously that it is not possible to make rational and consistent decisions in
case sequencing without knowing how long each case (including diagnostic imaging
procedures) can wait to be started without a change in the patient's risk. The
scheduled surgical procedure itself provides sufficient information to assess
safe waiting times to start add-on cases (e.g., appendectomy). In contrast, MRI
provides no context as to how potential findings will influence treatment. Our
results show that the assumption cannot reasonably be made when sequencing cases
that all imaging studies can or cannot wait longer than pending surgical
procedures. Our results show that, for evidence-based OR management decision
making, information to decide appropriate waiting should be obtained
electronically or verbally for each imaging study.
PMID- 26417916
TI - In Situ Analysis of Gas Generation in Lithium-Ion Batteries with Different
Carbonate-Based Electrolytes.
AB - Gas generation in lithium-ion batteries is one of the critical issues limiting
their safety performance and lifetime. In this work, a set of 900 mAh pouch cells
were applied to systematically compare the composition of gases generated from a
serial of carbonate-based composite electrolytes, using a self-designed gas
analyzing system. Among electrolytes used in this work, the composite gamma
butyrolactone/ethyl methyl carbonate (GBL/EMC) exhibited remarkably less gassing
because of the electrochemical stability of the GBL, which makes it a promising
electrolyte for battery with advanced safety and lifetime.
PMID- 26417917
TI - Siege of Leningrad Survivors Phenotyping and Biospecimen Collection.
AB - BACKGROUND: Poor nutrition during the early stages of human development can lead
to rare pathological conditions in adult life. The best-known and most severe
historical cases of famine include the Dutch 'Hunger Winter,' the Finnish famine,
the Chinese Great famine, and the siege of Leningrad. The siege of Leningrad (now
Saint Petersburg) was one of the longest in history, lasting 872 days, from
September 8, 1941 to January 27, 1944. There were 670,000 registered deaths of
the civil population, in which 97% died due to starvation. The aim of the present
study is to create a collection of biospecimens from extensively phenotyped siege
of Leningrad survivors, who underwent starvation during the early periods of
their lives, and from a matched control group. METHODS: A total 305 siege
survivors and 51 age- and sex- matched control subjects were investigated in of
an observational retroprospective cohort study in 2009-2011 at a baseline visit.
After 3 years of follow-up, 252 siege survivors (182 females and 70 males; mean
age 74.7 +/- 2.6 years) and 45 controls (32 females and 13 males; mean age 75.5
+/- 2.8 years) were examined. All siege survivors were exposed to the extreme
dietary restriction and stress associated with the siege in their early
childhood. All participants signed informed consent and were subject to
questionnaires and physical examination, as well as various laboratory and
instrumental tests. Anthropometry, blood measurement, cognitive and physiological
testing, and vascular damage assessment were performed. RESULTS: Blood specimens
of the extensively phenotyped siege survivors were collected and processed (blood
plasma, blood serum, and flash-frozen PBMC); serum and urine were used for
laboratory tests. CONCLUSIONS: We believe that data obtained from this unique
collection of biospecimens can elucidate the mechanisms of healthy aging and
emphasize the importance of reproductive health, counseling, and monitoring among
people with eating disorders.
PMID- 26417918
TI - Picosecond Dynamics of Excitonic Magnetic Polarons in Colloidal Diffusion-Doped
Cd(1-x)Mn(x)Se Quantum Dots.
AB - Spontaneous magnetization is observed at zero magnetic field in photoexcited
colloidal Cd(1-x)Mn(x)Se (x = 0.13) quantum dots (QDs) prepared by diffusion
doping, reflecting strong Mn(2+)-exciton exchange coupling. The picosecond
dynamics of this phenomenon, known as an excitonic magnetic polaron (EMP), are
examined using a combination of time-resolved photoluminescence, magneto
photoluminescence, and Faraday rotation (TRFR) spectroscopies, in conjunction
with continuous-wave absorption, magnetic circular dichroism (MCD), and magnetic
circularly polarized photoluminescence (MCPL) spectroscopies. The data indicate
that EMPs form with random magnetization orientations at zero external field, but
their formation can be directed by an external magnetic field. After formation,
however, external magnetic fields are unable to reorient the EMPs within the
luminescence lifetime, implicating anisotropy in the EMP potential-energy
surfaces. TRFR measurements in a transverse magnetic field reveal rapid (<5 ps)
spin transfer from excitons to Mn(2+) followed by coherent EMP precession at the
Mn(2+) Larmor frequency for over a nanosecond. A dynamical TRFR phase inversion
is observed during EMP formation attributed to the large shifts in excitonic
absorption energies during spontaneous magnetization. Partial optical orientation
of the EMPs by resonant circularly polarized photoexcitation is also
demonstrated. Collectively, these results highlight the extraordinary physical
properties of colloidal diffusion-doped Cd(1-x)Mn(x)Se QDs that result from their
unique combination of strong quantum confinement, large Mn(2+) concentrations,
and relatively narrow size distributions. The insights gained from these
measurements advance our understanding of spin dynamics and magnetic exchange in
colloidal doped semiconductor nanostructures, with potential ramifications for
future spin-based information technologies.
PMID- 26417919
TI - Factors Leading to Rapid Response Team Interventions in Adult Medical-Surgical
Patients.
AB - The effectiveness of a Rapid Response Team Intervention (RRTI) in preventing
transfer to a higher level of care and decreasing in-hospital mortality has not
been firmly established. This retrospective exploratory study examined
differences between medical-surgical patients who had an RRTI and those who did
not. Results yielded 5 statistically significant differences (P <= .05) between
the 2 groups as well as a large variation (range, 0-238 minutes; SD = 87.73
minutes) between time of documentation of RRTI criteria to time in calling an
RRTI.
PMID- 26417920
TI - Systematic Review of Control Measures to Reduce Hazardous Drug Exposure for
Health Care Workers.
AB - Because of their involvement in the transport, handling, preparation,
administration, or disposal of hazardous medications, health care workers across
multiple settings are at risk for adverse health consequences from exposure to
these drugs. This review presents evidence-based strategies to mitigate the
harmful exposures. These include engineering controls, full use of personal
protective equipment, medical and environmental monitoring, hazard
identification, and the need for a comprehensive hazardous drug control program
that includes education and training for health care workers.
PMID- 26417921
TI - Significant differences of monooxotungsten(IV) and dioxotungsten(VI)
benzenedithiolates containing two intramolecular NHS hydrogen bonds from
molybdenum analogues.
AB - A monooxotungsten(iv) benzenedithiolate complex containing two intramolecular NHS
hydrogen bonds, (NEt4)2[W(IV)O(1,2-S2-3-t-BuNHCOC6H3)2] (1-W), was synthesized
via a ligand-exchange reaction between a new starting complex,
(NEt4)2[W(IV)O(SC6F5)4], and a partially deprotonated dithiol. When dithiol was
used in solution, the oxo ligand was protonated and removed to afford
(NEt4)2[W(IV)(1,2-S2-3-t-BuNHCOC6H3)3]. The trans isomer, trans-1-W, was
crystallized, and the molecular structure was determined via X-ray analysis.
Trans-1-W was gradually isomerized by heating it in solution and it eventually
achieved an approximately 1 : 1 mixture of trans/cis isomers after 48 days.
However, a slightly excess amount of trans isomer remained, so the isomerization
rate was considerably slower than that of the molybdenum analogue. In the
presence of NEt4BH4, deuteration of the NH protons was observed in acetonitrile
d3. The oxidation of both trans- and cis-1-W by Me3NO afforded the corresponding
dioxotungsten(vi) complex, (NEt4)2[W(VI)O2(1,2-S2-3-t-BuNHCOC6H3)2] (2-W), as a
single isomer. The contributions of the NHS hydrogen bonds to the bond distances,
vibrational data, and electrochemical properties are described via comparisons
with their molybdenum analogues. The results of this comparative study yielded
insights into both tungsten and molybdenum enzymes.
PMID- 26417922
TI - Formaldehyde as Tethering Organocatalyst: Highly Diastereoselective
Hydroaminations of Allylic Amines.
AB - Catalysts possessing sufficient activity to achieve intermolecular alkene
hydroaminations under mild conditions are rare, and this likely accounts for the
scarcity of asymmetric variants of this reaction. Herein, highly
diastereoselective hydroaminations of allylic amines utilizing hydroxylamines as
reagents and formaldehyde as catalyst are reported. This catalyst induces
temporary intramolecularity, which results in high rate accelerations, and high
diastereocontrol with either chiral allylic amines or chiral hydroxylamines. The
reaction scope includes internal alkenes. Overall this work provides a new,
stereocontrolled route to form complex vicinal diamines.
PMID- 26417923
TI - The Growth of Palliative Care in U.S. Hospitals: A Status Report.
AB - BACKGROUND: Palliative care is expanding rapidly in the United States. OBJECTIVE:
To examine variation in access to hospital palliative care. METHODS: Data were
obtained from the American Hospital Association (AHA) Annual SurveysTM for Fiscal
Years 2012 and 2013, the National Palliative Care RegistryTM, the Dartmouth Atlas
of Healthcare, the American Census Bureau's American Community Survey (ACS), web
searches, and telephone interviews of hospital administrators and program
directors. Multivariable logistic regression was used to examine predictors of
hospital palliative care programs. RESULTS: Sixty-seven percent of hospitals with
50 or more total facility beds reported a palliative care program. Institutional
characteristics were strongly associated with the presence of a hospital
palliative care program. Ninety percent of hospitals with 300 beds or more were
found to have palliative care programs as compared to 56% of hospitals with fewer
than 300 beds. Tax status was also a significant predictor. Not-for-profit
hospitals and public hospitals were, respectively, 4.8 times and 7.1 times more
likely to have a palliative care program as compared to for-profit hospitals.
Palliative care penetration was highest in the New England (88% of hospitals),
Pacific (77% of hospitals), and mid-Atlantic (77% of hospitals) states and lowest
in the west south central (43% of hospitals) and east south central (42% of
hospitals) states. CONCLUSIONS: This study demonstrates continued steady growth
in the number of hospital palliative care programs in the United States, with
almost universal access to services in large U.S. hospitals and academic medical
centers. Nevertheless access to palliative care remains uneven and depends on
accidents of geography and hospital ownership.
PMID- 26417925
TI - Comparative study of van der Waals corrections to the bulk properties of
graphite.
AB - Graphite is a stack of honeycomb (graphene) layers bound together by nonlocal,
long-range van der Waals (vdW) forces, which are poorly described by density
functional theory (DFT) within local or semilocal exchange-correlation
functionals. Several approximations have been proposed to add a vdW correction to
the DFT total energies (Stefan Grimme (D2 and D3) with different damping
functions (D3-BJ), Tkatchenko-Scheffler (TS) without and with self-consistent
screening (TS + SCS) effects). Those corrections have remarkly improved the
agreement between our results and experiment for the interlayer distance (from
3.9 to 0.6%) [corrected] and high-level random-phase approximation (RPA)
calculations for interlayer binding energy (from 69.5 to 1.5%). [corrected]. We
report a systematic investigation of various structural, energetic and electron
properties with the aforementioned vdW corrections followed by comparison with
experimental and theoretical RPA data. Comparison between the resulting relative
errors shows that the TS + SCS correction provides the best results; the other
corrections yield significantly larger errors for at least one of the studied
properties. If considerations of computational costs or convergence problems rule
out the TS + SCS approach, we recommend the D3-BJ correction. Comparison
between the computed pi(z)Gamma-splitting and experimental results shows
disagreements of 10% or more with all vdW corrections. Even the computationally
more expensive hybrid PBE0 has proved unable to improve the agreement with the
measured splitting. Our results indicate that improvements of the exchange
correlation functionals beyond the vdW corrections are necessary to accurately
describe the band structure of graphite.
PMID- 26417924
TI - Thioredoxins in cardiovascular disease.
AB - Key thioredoxin (Trx) system components are nicotinamide adenine dinucleotide
phosphate (NADPH), Trx reductase (TrxR), and Trx. TrxR catalyzes disulfide
reduction in Trx with NADPH as cofactor. Because Trx is an antioxidant, oxidative
stress results in an increase in Trx, which has a reduced disulfide component. If
Trx is suppressed, oxidative stress in higher. In contrast a decrease in
oxidative stress is associated with low Trx levels. Trx is involved in
inflammation, apoptosis, embryogenesis, and cardiovascular disease (CVD). This
review focuses on the Trx system in CVD. Abnormal Trx binding occurs in mouse
familial combined hyperlipidemia; however, this has not been confirmed in humans.
Congestive heart failure is a manifestation of many CVDs, which may be improved
by attenuating oxidative stress through the suppression of Trx and decreased
reactive oxygen species. Angiotensin II is associated with hypertension and other
CVDs, and its receptor blockade results in decreased oxidative stress with
reduced Trx levels. Inflammation is a major causative factor of CVDs, and
myocarditis as an example, is associated with increased Trx levels. Vascular
endothelial dysfunction has an association with CVD. This dysfunction is
alleviated by hormone replacement therapy, which involves decreased oxidative
stress and Trx levels. Diabetes mellitus has a major association with CVDs;
increase in Trx levels may reflect insulin resistance. Identification of Trx
system abnormalities may lead to innovative approaches to treat multiple CVDs and
other pathologies.
PMID- 26417926
TI - Femtosecond Laser Flap Creation for Laser In Situ Keratomileusis in the Setting
of Previous Radial Keratotomy.
AB - PURPOSE: The aim of the study was to report the outcomes of laser in situ
keratomileusis (LASIK) in subjects with previous radial keratotomy (RK) using a
novel femtosecond laser setting on a proprietary femtosecond laser platform.
DESIGN: This was a retrospective, consecutive chart review of patients at a
single private practice institution. METHODS: The medical records of 16 eyes of 8
subjects who underwent femtosecond-assisted LASIK for consecutive hyperopia after
RK were retrospectively reviewed. The preoperative characteristics,
intraoperative details, and postoperative outcomes were analyzed. RESULTS: All 16
eyes had successful femtosecond laser flap creation without significant
intraoperative or postoperative complications. Uncorrected visual acuity
significantly improved postoperatively (P = 0.0142) and remained stable through
the final follow-up interval at 9 to 12 months postoperatively. None of the
subjects lost any lines of best spectacle-corrected visual acuity in the
postoperative period. CONCLUSIONS: The novel femtosecond laser technique
described in this study can provide a safe and effective method for patients
undergoing LASIK after previous RK. Future investigations are required to further
validate the findings reported in this study.
PMID- 26417927
TI - Visual Performance After Contralateral Implantation of Multifocal Intraocular
Lenses With +3.0 and +4.0 Diopter Additions.
AB - PURPOSE: To evaluate visual performance after contralateral implantation of
AcrySof ReSTOR aspheric intraocular lenses (IOLs) with +3.0 and +4.0 diopter near
additions. DESIGN: This was a retrospective case study conducted at Tokyo Dental
College Suidobashi Hospital in Tokyo, Japan. METHODS: Eleven patients who were
implanted with the SN6AD1 IOL and the SN6AD3 IOL contralaterally were included in
this study. The distance, intermediate (1 m, 50 cm), and near (40 and 30 cm)
uncorrected and corrected binocular visual acuity (VA), contrast sensitivity,
depth of focus, and patient satisfaction were assessed more than 1 month
postoperatively. RESULTS: Postoperatively, the mean uncorrected (corrected)
binocular logarithm of the minimum angle of resolution VA levels were as follows:
distance, -0.120 (-0.163); intermediate, 1 m, 0.226 (0.012) and 50 cm, 0.037
(0.006); and near, 40 cm, 0.067 (-0.040) and 30 cm, 0.091 (-0.053). The depth of
focus had a smooth curve with double peaks. The mean contrast sensitivity was
normal at all spatial frequencies. All patients were spectacle independent and
expressed high satisfaction. CONCLUSIONS: Contralateral implantation of
multifocal IOLs with +3.0 and +4.0 D additions takes advantage of the good
uncorrected near VA provided by both IOLs and may be an option for patients who
require a broader range of good uncorrected near VA.
PMID- 26417928
TI - Neuro-Ophthalmology Annual Review.
AB - PURPOSE: The purpose of this review was to update the practicing ophthalmologist
on the English language neuro-ophthalmology literature from the past year.
DESIGN: A review of English language literature from August 1, 2013, to August 1,
2014, was conducted. METHODS: The author searched PubMed from August 1, 2013, to
August 1, 2014, limited to English language publications including original
articles, review articles, and case reports and excluding letters to the editor,
unpublished work, and abstracts. The following topics were searched: pupillary
abnormalities, eye movement dysfunction, neuromuscular diseases, optic
neuropathies, optic neuritis, demyelinating diseases including multiple
sclerosis, lesions of the optic chiasm and posterior primary visual pathways,
elevated intracranial pressure, tumors and aneurysms affecting the visual
pathways, vascular diseases, higher visual function, and neuroimaging advances.
The focus of this review is on clinically relevant literature in the past year
for the practicing ophthalmologist. The aim was to highlight remarkable and
interesting literature rather than exhaustively including all new neuro
ophthalmological publications of the year. RESULTS: Initially, more than 11,000
articles were identified. One hundred were selected that met criteria specified
above. CONCLUSIONS: This review updates the comprehensive ophthalmologist on
neuro-ophthalmic topics.
PMID- 26417929
TI - Cytotoxic T cell responses are enhanced by antigen design involving the
presentation of MUC1 peptide on cholera toxin B subunit.
AB - Induction of cytotoxic T lymphocytes (CTL) is critical to cancer vaccine based
immunotherapy. Efforts to elicit CTLs against tumor MUC1 with peptide based
vaccine have not been successful in clinical application. We have design a MUC1
vaccine by replacing B cell epitope of CTB with MUC1 VNTR peptide. Immunization
with hybrid CTB-MUC1 plus aluminum hydroxide and CpG adujuvant (CTB-MUC1-Alum
CpG) induce MUC1-specific CTLs in mice. Moreover, this vaccination can prevent
tumor growth and reduce tumor burden in MUC1+B16 mice model. Meanwhile, CTB-MUC1
Alum-CpG vaccination can promote Th1 cells and CD8+ T cells inflate to tumor
tissue. Our approach might be applicable to other cancer vaccine design.
PMID- 26417930
TI - The G-protein-coupled bile acid receptor Gpbar1 (TGR5) suppresses gastric cancer
cell proliferation and migration through antagonizing STAT3 signaling pathway.
AB - Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well known for its roles
in regulation of energy homeostasis and glucose metabolism. Here we show that
TGR5 is a suppressor of gastric cancer cell proliferation and migration through
antagonizing STAT3 signaling pathway. We firstly show that TGR5 activation
greatly inhibited proliferation and migration of human gastric cancer cells and
strongly induced gastric cancer cell apoptosis. We then found that TGR5
activation antagonized STAT3 signaling pathway through suppressing the
phosphorylation of STAT3 and its transcription activity induced by
lipopolysaccharide (LPS) or interleukin-6. TGR5 overexpression with ligand
treatment inhibited gene expression mediated by STAT3. It suggests that TGR5
antagonizes gastric cancer proliferation and migration at least in part by
inhibiting STAT3 signaling. These findings identify TGR5 as a suppressor of
gastric cancer cell proliferation and migration that may serve as an attractive
therapeutic tool for human gastric cancer.
PMID- 26417931
TI - MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in
breast cancer cells.
AB - MicroRNAs (miRNAs) are key regulators of tumor progression. Based on microarray
data, we identified miR-99a as a potential tumor suppressor in breast cancer.
Expression of miR-99a is frequently down-regulated in breast cancer tissues
relative to normal breast tissues. Reduced miR-99a expression was highly
associated with lymph node metastasis and shorter overall survival of patients
with breast cancer. Gain- and loss-of-function studies revealed that, miR-99a
significantly inhibits breast cancer cell proliferation, migration, and invasion.
An integrated bioinformatics analysis identified HOXA1 mRNA as the direct
functional target of miR-99a, and this regulation was confirmed by luciferase
reporter assay. Furthermore, we showed for the first time that HOXA1 expression
is elevated in breast cancer tissues. Knockdown of HOXA1 significantly inhibited
breast cancer cell proliferation, migration and invasion, and restoration of
HOXA1 partially rescued the inhibitory effect of miR-99a in breast cancer cells.
Collectively, our data indicate that miR-99a plays a tumor-suppressor role in the
development of breast cancer, and could serve as a potential therapeutic target
for breast cancer treatment.
PMID- 26417934
TI - Early and mid-term outcomes of a novel Endovascular Aneurysm Sealing (EVAS)
system in patients with infrarenal Abdominal Aortic Aneurysms.
AB - BACKGROUND: Endovascular aneurysm sealing (EVAS) using the Nellix system is a
promising technology for Abdominal Aortic Aneurysm (AAA) treatment. Long-term
data is unavailable regarding the potential modifications of the EndoBags and
their content, and the polymer behavior over time. We present our initial
clinical experience with this sac anchoring endoprosthesis in 24 patients with a
maximum 12 months follow-up. METHODS AND RESULTS: From December 2013 to March
2015, 24 patients with an infrarenal AAA were treated with the NellixTM System.
Computed Tomography Angiography (CTA) scan control was performed at 30 days, and
follow-up Magnetic Resonance Angiography (MRA) and ultrasounds were performed at
30 days, 6 and 12 months. Median and peak systolic velocities in the suprarenal
aorta were measured preoperatively and during follow-up using phase contrast
sequences and Argus (Siemens, Erlangen, Germany) software of the MRA. We achieved
100% technical success, 0% aneurysm-related mortality and 0% endoleaks. One
patient (4%) experienced early acute thrombosis of a single Nellix stent,
successfully treated with thrombolysis. Sac shrinkage occurred in 80% of cases
with 12 months follow-up. CONCLUSIONS: Our preliminary clinical experience is
promising, with 100% early technical success and satisfactory sealing of the
aneurysm sac. Post-procedural controls during 1-year- follow-up revealed no
morphologic changes of the aneurysm wall, stable device and endobag position, and
gradual dissolution of the air initially trapped within the EndoBags. Aneurysmal
sac shrinkage occurs and probably is due to the remodeling of the thrombus around
the EndoBags and the dissipation of the air bubbles into the EndoBags.
PMID- 26417932
TI - Wnt/beta-catenin, an oncogenic pathway targeted by H. pylori in gastric
carcinogenesis.
AB - A section of gastric cancers presents nuclear beta-catenin accumulation
correlated with H. pylori infection. H. pylori stimulate Wnt/beta-catenin pathway
by activating oncogenic c-Met and epidermal growth factor receptor (EGFR), or by
inhibiting tumor suppressor Runx3 and Trefoil factor 1 (TFF1). H. pylori also
trigger Wnt/beta-catenin pathway by recruiting macrophages. Moreover, Wnt/beta
catenin pathway is found involved in H. pylori-induced gastric cancer stem cell
generation. Recently, by using gastroids, researchers have further revealed that
H. pylori induce gastric epithelial cell proliferation through beta-catenin.
These findings indicate that Wnt/beta-catenin is an oncogenic pathway activated
by H. pylori. Therefore, this pathway is a potential therapy target for H. pylori
related gastric cancer.
PMID- 26417933
TI - Nickel chloride (NiCl2)-caused inflammatory responses via activation of NF-kappaB
pathway and reduction of anti-inflammatory mediator expression in the kidney.
AB - Nickel (Ni) or Ni compounds target a number of organs and produce multiple toxic
effects. Kidney is the major organ for Ni accumulation and excretion. There are
no investigations on the Ni- or Ni compounds-induced renal inflammatory responses
in human beings and animals at present. Therefore, we determined NiCl2-caused
alteration of inflammatory mediators, and functional damage in the broiler's
kidney by the methods of biochemistry, immunohistochemistry and quantitative real
time polymerase chain reaction (qRT-PCR). Dietary NiCl2 in excess of 300 mg/kg
caused the renal inflammatory responses that characterized by increasing mRNA
expression levels of the pro-inflammatory mediators including tumor necrosis
factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), interleukin-1beta (IL-1beta),
interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) via the
activation of nucleic factor kappaB (NF-kappaB), and decreasing mRNA expression
levels of the anti-inflammatory mediators including interleukin-2 (IL-2),
interleukin-4 (IL-4) and interleukin-13 (IL-13). Concurrently, NiCl2 caused
degeneration, necrosis and apoptosis of the tubular cells, which was consistent
with the alteration of renal function parameters including elevated alkaline
phosphatase (AKP) activity, and reduced activities of sodium-potassium adenosine
triphosphatase (Na(+)/K(+)-ATPase), calcium adenosine triphosphatase (Ca(2+)
ATPase), lactic dehydrogenase (LDH), succinate dehydrogenase (SDH) and acid
phosphatase (ACP) in the kidney. The above-mentioned results present that the
activation of NF-kappaB pathway and reduction of anti-inflammatory mediator
expression are main mechanisms of NiCl2-caused renal inflammatory responses and
that the renal function is decreased or impaired after NiCl2-treated.
PMID- 26417936
TI - The endovascular treatment of juxta-renal abdominal aortic aneurysm using
fenestrated endograft: early and mid-term results.
AB - AIM: To evaluate the early and mid term results of the endovascular treatment of
juxta-renal abdominal aortic aneurysms (j-AAA) using fenestrated endograft
(FEVAR). METHODS: Between 2008 to 2013 all consecutive patients underwent FEVAR
using Cook-Zenith fenestrated endograft for treating j-AAA (proximal neck length
<5mm) with renal aortic alpha/beta angle < 60 degrees , were prospectively
collected in a database. Cardiovascular risk factors, co-morbidities, aortic-
iliac morphological features, intra and post-procedural data were analyzed. Pre
operative FEVAR planning was performed by a thoraco-abdominal computer tomography
angiography (CTA) and the 3D/Center Lumen Line reconstructions (3Mensio). Follow
up was conduced by duplex ultrasound (DUS)/ contrast enhancement DUS (CEUS)
and/or CTA at 1,6,12-month and yearly thereafter. Early endpoints were: technical
(TS) / clinical (CS) success, renal function worsening (>= 30% of pre- operative
creatinine value) and type I/III endoleak. Mid term endpoints were: type I/III
endoleak, target visceral vessels patency, j-AAA shrinkage, freedom from re
intervention and survival. RESULTS: Twenty patients (M: 94.7%; mean age: 73.4+/
5.9 years; ASA >=3: 100%) were enrolled. The mean neck length and j-AAA diameter
were 2 +/- 1.4mm (range: 0-4mm) and 54.9 +/-5mm respectively. Eleven (55%)
endograft with 2 fenestrations and a scallop, 8 (45%) with 3 fenestrations and a
scallop and 1 (5%) with 1 fenestration and a scallop were implanted. Sixty-seven
visceral vessels were re-vascularized. TS and CS were 100% and 95% respectively
(1/20 30-day mortality). Peri-operative renal function worsening was observed in
15% of cases. The mean follow-up was 25+/-20 months (range: 2-72months). No type
I/III endoleak or occlusion of target visceral vessels occurred. There was j-AAA
shrinkage in 65% of patients and no cases of j-AAA enlargement were observed.
There were no FEVAR-related re-interventions. Survival at 12, 24 and 36 months
were 89.4%, 80.5% e 80.5% respectively. CONCLUSION: According to our results, the
endovascular treatment for j-AAA, with alpha/beta angle < 60 degrees , is safe
and effective.
PMID- 26417935
TI - First experience with the new Sorin Crown PRT bioprosthetic aortic valve: early
postoperative outcome and hemodynamic performance in 90 patients.
AB - AIM: The Crown PRT (The Phospholipid Reduction Treatment) is a new stent bovine
bioprosthesis for aortic valve replacement (AVR). Aim of this paper is to report
the postoperative clinical and hemodynamic results after ninety consecutive
implants. METHODS: After receiving CE mark in July 2014, two European university
centers implanted the new Crown PRT (Sorin Group, Burnaby, Canada) for the first
time. Up to now, ninety patients underwent aortic valve replacement, in isolated
or combined procedures, for aortic stenosis or insufficiency. Intraoperative
transesophageal echocardiogram was used to assess the prosthesis's function. In
hospital outcomes and echocardiographic parameters were recorded. RESULTS: Age
and Log Euroscore were 71.8+/-7.9 years and 10.2%+/-4.5 respectively. In-hospital
mortality for isolated AVR was 0%; one patient died after a multiple procedure
(overall 30-days mortality 1.1%). No adverse device effects were recorded.
Intensive Care Unit stay was 2+/-5.8 days. At discharge, echocardiogram showed no
paravalvular leaks and normal postoperative gradients. CONCLUSION: Our starting
results showed that the Crown PRT is safe and reliable, with excellent
hemodynamic performance. Further clinical results with a larger population and
long term follow-up are needed to assess the versatility and the durability of
this new device.
PMID- 26417937
TI - Abdominal aortic aneurysm.
AB - Endovascular repair of abdominal aortic aneurysm has become a milestone in the
treatment of patients with abdominal aortic aneurysm.Technological improvement
allows treatment in more and more complex cases. This review summarizes all
grafts available in the market. At the best of our knowledge a complete review of
most important trial on this topic are provided and at least technical tips and
tricks for standard cases are recapitulated.
PMID- 26417938
TI - Hydrogen peroxide-independent generation of superoxide catalyzed by soybean
peroxidase in response to ferrous ion.
AB - It is well documented that extracellular alkalization occurs in plants under the
challenges by pathogenic microbes. This may eventually induce the pH-dependent
extracellular peroxidase-mediated oxidative burst at the site of microbial
challenges. By employing the purified proteins of horseradish peroxidase as a
model, we have recently proposed a likely role for free Fe(2+) in reduction of
ferric enzyme of plant peroxidases into ferrous intermediate and oxygen-bound
form of enzyme known as Compound III which may eventually releases superoxide
anion radical (O2(*-)), especially under alkaline condition, possibly
contributing to the plant defense mechanism. In the present study, we employed
the purified protein of soybean peroxidase (SBP) as an additional model, and
examined the changes in the redox status of enzyme accompanying the generation of
O2(*-) in response to Fe(2+) under alkaline condition.
PMID- 26417940
TI - Anatomical and Morphological Features of the Fetal Human Pancreaticobiliary
Ductal Union.
AB - To investigate pancreaticobiliary ductal anatomy during developmental stages,
gallbladders, common bile ducts, pancreatic ducts and their interface with the
duodenum were studied in 36 human fetuses between 4-6 weeks postconceptual age
were studied. For histological examination, sections were cut continuously from
the paraffin-embedded tissue block and stained with hematoxylin and eosin. The
expression of proliferating cell nuclear antigen in the gallbladder was examined
with immunohistochemistry. Among 36 cases, three shapes of the greater duodenal
papilla were found: hemispheroid (58.1%), circular cylinder (25%), and flat shape
(16.9%). For the location of the greater duodenal papillas, more than half
(69.4%) of the cases were in the middle descendant duodenum. Seven cases (19.4%)
were in the lower descendant duodenum. Three cases (8.3%) were in the upper
descendant duodenum, and one (2.9%) was in the distal descending part of
duodenum. There were four types of the pancreaticobiliary ductal union: "Y" in 24
cases(66.7%), "U" in 4 cases (11.1%),"V" in 7 cases (19.4%), and
pancreaticobiliary maljunction in 1 case (2.8%). For patients with congenital
bile duct dilation and Biliary cancer, the positive cells of proliferating cell
nuclear antigen were increased significantly (P < 0.05). Different types in
pancreaticobiliary ductal union investigated in this study may provide clues for
pathogenesis and clinical treatment of pancreaticobiliary maljunction.
PMID- 26417939
TI - ADAM12 and PAPP-A: Candidate regulators of trophoblast invasion and first
trimester markers of healthy trophoblasts.
AB - Proper placental development and function is crucial for a healthy pregnancy, and
there has been substantial research to identify markers of placental dysfunction
for the early detection of pregnancy complications. Low first-trimester levels of
a disintegrin and metalloproteinase 12 (ADAM12) and pregnancy-associated plasma
protein-A (PAPP-A) have been consistently associated with the subsequent
development of preeclampsia and fetal growth restriction. These molecules are
both metalloproteinases secreted by the placenta that cleave insulin-like growth
factor binding proteins (IGFBPs), although ADAM12 also has numerous other
substrates. Recent work has identified ADAM12, and particularly its shorter
variant, ADAM12S, as a regulator of the migration and invasion of trophoblasts
into the lining of the uterus, a critical step in normal placental development.
While the mechanisms underlying this regulation are not yet clear, they may
involve the liberation of heparin-binding EGF-like growth factor (HB-EGF) and/or
IGFs from IGFBPs. In contrast, there has been relatively little functional work
examining PAPP-A or the IGFBP substrates of ADAM12 and PAPP-A. Understanding the
functions of these markers and the mechanisms underlying their association with
disease could improve screening strategies and enable the development of new
therapeutic interventions.
PMID- 26417941
TI - Diffusion of Benzene and Alkylbenzenes in n-Alkanes.
AB - The translational diffusion constants, D, of benzene and a series of
alkylbenzenes have been determined in four n-alkanes at room temperature using
capillary flow techniques. The alkylbenzenes are toluene, ethylbenzene, 1
phenylpropane, 1-phenylpentane, 1-phenyloctane, 1-phenylundecane, 1
phenyltetradecane, and 1-phenylheptadecane. The n-alkanes are n-nonane, n-decane,
n-dodecane, and n-pentadecane. Ratios of the solutes' D values are independent of
solvent and in general agreement with the predictions of diffusion models for
cylinders and lollipops. For the latter, an alkylbenzene's phenyl ring is the
lollipop's candy; the alkyl chain is its handle. A model that considers the
solutes to be spheres with volumes determined by the van der Waals increments of
their constituent atoms is not in agreement with experiment. The diffusion
constants of 1-alkene and n-alkane solutes in n-alkane solvents also are compared
with the cylinder model; reasonably good agreement is found. The n-alkanes are
relatively extended, and this appears to be the case for the alkyl chains of the
1-alkenes and alkylbenzenes as well.
PMID- 26417943
TI - Synthetic and Structural Studies of Mixed Sodium Bis(trimethylsilyl)amide/Sodium
Halide Aggregates in the Presence of eta(2)-N,N-, eta(3)-N,N,N/N,O,N-, and eta(4)
N,N,N,N-Donor Ligands.
AB - When n-hexane solutions of an excess of sodium bis(trimethylsilyl)amide (NaHMDS)
are combined with cesium halide (halide = Cl, Br, or I) in the presence of the
tetradentate donor molecule [tris[2-(dimethylamino)ethyl]amine] (Me6TREN), the
isolation and characterization of a series of sodium amide/sodium halide mixed
aggregates was forthcoming. Cesium halide was employed because it efficiently
reacted with NaHMDS to produce a molecular, soluble source of sodium halide salt
(which was subsequently captured by an excess of NaHMDS) via a methathetical
reaction. These mixed sodium amide/sodium halide complexes are formally sodium
sodiates, are deficient in halide with respect to the amide, and have the general
formula [{Na5(MU-HMDS)5(MU5-X)}{Na(Me6TREN)}] [where X = Cl (1), Br (2), or I
(3)]. The influence of the donor ligand was studied for the NaI/NaHMDS system,
and when n-hexane solutions of this composition were treated with tridentate
donors such as N,N,N',N",N"-pentamethyldiethylenetriamine (PMDETA) or N,N,N',N'
tetramethyldiaminoethyl ether (TMDAE), solvent-separated ion-pair cocomplexes
[Na5(MU-HMDS)5(MU5-I)](-)[Na3(MU-HMDS)2(PMDETA)2](+) (4) and [Na5(MU-HMDS)5(MU5
I)](-)[Na(TMDAE)2](+) (5) were isolated. However, upon reaction with bidentate
proligands such as the chiral diamine (R,R)-N,N,N',N'-tetramethylcyclohexane-1,2
diamine [(R,R)-TMCDA] or N,N,N',N'-tetramethylethylenediamine (TMEDA), neutral
complexes [Na4(MU-HMDS)3(MU4-I)(donor)2] [donor = (R,R)-TMCDA (6) and TMEDA (7)]
were produced. To illustrate the generality of the latter reaction with other
halides, [Na4(MU-HMDS)3(MU4-Br)(TMEDA)2] (8) was also prepared by employing NaBr
in the synthesis instead of NaI.
PMID- 26417942
TI - Behavioral associations with waterpipe tobacco smoking dependence among US young
adults.
AB - BACKGROUND AND AIMS: Waterpipe tobacco smoking (WTS) is increasingly prevalent in
the United States, especially among young adults. We aimed to (1) adapt items
from established dependence measures into a WTS dependence scale for US young
adults (the US Waterpipe Dependence Scale), (2) determine the factor structure of
the items and (3) assess associations between scale values and behavioral use
characteristics known to be linked to dependence. DESIGN: Cross-sectional survey.
SETTING: United States. PARTICIPANTS: A total of 436 past-year waterpipe tobacco
users ages 18-30 years selected at random from a national probability-based
panel. MEASUREMENTS: Participants responded to six tobacco dependence items
adapted for WTS in US populations. Behavioral use characteristics included
factors such as frequency of use and age of initiation. FINDINGS: Principal
components analysis yielded an unambiguous one-factor solution. Approximately
half (52.9%) of past-year waterpipe tobacco users received a score of 0,
indicating that none of the six WTS dependence items were endorsed. Approximately
one-quarter (25.4%) endorsed one dependence item and 22.7% endorsed two or more
items. Higher WTS dependence scores were associated significantly with all five
behavioral use characteristics. For example, compared with those who endorsed no
dependence items, those who endorsed two or more had an adjusted odds ratio (AOR)
of 3.90 [95% confidence interval (CI) = 1.56-9.78] for having had earlier age of
initiation and an AOR of 32.75 (95% CI = 9.76-109.86) for more frequent WTS
sessions. CONCLUSIONS: Scores on a six-item waterpipe tobacco smoking dependence
scale (the US Waterpipe Dependence Scale) correlate with measures that would be
expected to be related to dependence, such as amount used and age of initiation.
PMID- 26417945
TI - Correction: Bacillus anthracis Diversity and Geographic Potential across Nigeria,
Cameroon and Chad: Further Support of a Novel West African Lineage.
PMID- 26417944
TI - Neuromodulation to the Rescue: Compensation of Temperature-Induced Breakdown of
Rhythmic Motor Patterns via Extrinsic Neuromodulatory Input.
AB - Stable rhythmic neural activity depends on the well-coordinated interplay of
synaptic and cell-intrinsic conductances. Since all biophysical processes are
temperature dependent, this interplay is challenged during temperature
fluctuations. How the nervous system remains functional during temperature
perturbations remains mostly unknown. We present a hitherto unknown mechanism of
how temperature-induced changes in neural networks are compensated by changing
their neuromodulatory state: activation of neuromodulatory pathways establishes a
dynamic coregulation of synaptic and intrinsic conductances with opposing effects
on neuronal activity when temperature changes, hence rescuing neuronal activity.
Using the well-studied gastric mill pattern generator of the crab, we show that
modest temperature increase can abolish rhythmic activity in isolated neural
circuits due to increased leak currents in rhythm-generating neurons. Dynamic
clamp-mediated addition of leak currents was sufficient to stop neuronal
oscillations at low temperatures, and subtraction of additional leak currents at
elevated temperatures was sufficient to rescue the rhythm. Despite the apparent
sensitivity of the isolated nervous system to temperature fluctuations, the
rhythm could be stabilized by activating extrinsic neuromodulatory inputs from
descending projection neurons, a strategy that we indeed found to be implemented
in intact animals. In the isolated nervous system, temperature compensation was
achieved by stronger extrinsic neuromodulatory input from projection neurons or
by augmenting projection neuron influence via bath application of the peptide
cotransmitter Cancer borealis tachykinin-related peptide Ia (CabTRP Ia). CabTRP
Ia activates the modulator-induced current IMI (a nonlinear voltage-gated inward
current) that effectively acted as a negative leak current and counterbalanced
the temperature-induced leak to rescue neuronal oscillations. Computational
modelling revealed the ability of IMI to reduce detrimental leak-current
influences on neuronal networks over a broad conductance range and indicated that
leak and IMI are closely coregulated in the biological system to enable stable
motor patterns. In conclusion, these results show that temperature compensation
does not need to be implemented within the network itself but can be
conditionally provided by extrinsic neuromodulatory input that counterbalances
temperature-induced modifications of circuit-intrinsic properties.
PMID- 26417946
TI - Grey-Theory-Based Optimization Model of Emergency Logistics Considering Time
Uncertainty.
AB - Natural disasters occur frequently in recent years, causing huge casualties and
property losses. Nowadays, people pay more and more attention to the emergency
logistics problems. This paper studies the emergency logistics problem with multi
center, multi-commodity, and single-affected-point. Considering that the path
near the disaster point may be damaged, the information of the state of the paths
is not complete, and the travel time is uncertainty, we establish the nonlinear
programming model that objective function is the maximization of time
satisfaction degree. To overcome these drawbacks: the incomplete information and
uncertain time, this paper firstly evaluates the multiple roads of transportation
network based on grey theory and selects the reliable and optimal path. Then
simplify the original model under the scenario that the vehicle only follows the
optimal path from the emergency logistics center to the affected point, and use
Lingo software to solve it. The numerical experiments are presented to show the
feasibility and effectiveness of the proposed method.
PMID- 26417947
TI - Correction: Reduced Topological Efficiency in Cortical-Basal Ganglia Motor
Network of Parkinson's Disease: A Resting State fMRI Study.
PMID- 26417948
TI - Functional Domains of ZFP809 Essential for Nuclear Localization and Gene
Silencing.
AB - Zinc finger protein 809 (ZFP809) is a member of the Kruppel-associated box
containing zinc finger protein (KRAB-ZFP) family, and is highly expressed in
mouse immature cells. ZFP809 is known to inhibit the expression of transduced
genes driven by Moloney murine leukemia virus (MoMLV)-typed retroviral vectors by
binding to the primer binding site (PBS) located downstream of the MLV-long
terminal repeat (LTR) of the vectors and recruiting protein complexes that
introduce epigenetic silencing marks such as histone modifications and DNA
methylation at the MLV-LTR. However, it remains undetermined what domains of
ZFP809 among the KRAB domain at N-terminus and the seven zinc fingers are
critical for gene silencing. In this study, we assessed subcellular localization,
gene silencing ability, and binding ability to the PBS of a series of truncated
and mutated ZFP809 proteins. We revealed the essential role of the KRAB A box for
all functions assessed, together with the accessory roles of a subset of zinc
fingers. Our data also suggest that interaction between KAP1 and the KRAB A box
of ZFP809 is critical in KAP1-dependent control of gene silencing for ZFP809
targets.
PMID- 26417950
TI - Corticostriatal dynamics encode the refinement of specific behavioral variability
during skill learning.
AB - Learning to perform a complex motor task requires the optimization of specific
behavioral features to cope with task constraints. We show that when mice learn a
novel motor paradigm they differentially refine specific behavioral features.
Animals trained to perform progressively faster sequences of lever presses to
obtain reinforcement reduced variability in sequence frequency, but increased
variability in an orthogonal feature (sequence duration). Trial-to-trial
variability of the activity of motor cortex and striatal projection neurons was
higher early in training and subsequently decreased with learning, without
changes in average firing rate. As training progressed, variability in
corticostriatal activity became progressively more correlated with behavioral
variability, but specifically with variability in frequency. Corticostriatal
plasticity was required for the reduction in frequency variability, but not for
variability in sequence duration. These data suggest that during motor learning
corticostriatal dynamics encode the refinement of specific behavioral features
that change the probability of obtaining outcomes.
PMID- 26417949
TI - Hospital Admission following Acute Kidney Injury in Kidney Transplant Recipients
Is Associated with a Negative Impact on Graft Function after 1-Year.
AB - The incidence and outcomes of acute kidney injury (AKI) in kidney transplantation
are poorly known. Retrospective cohort analysis was performed on the data of all
patients (>=3 months after transplantation and >=16 years of age) admitted to the
hospital due to medical or surgical complications from 2007 to 2010. We analyzed
458 kidney transplant recipients, 55.2% men, median age 49 (IQR, 36-58) years,
median of 12.5 (IQR, 3-35) months after kidney transplantation; admitted to the
hospital due to medical or surgical complications. Most of the patients received
a kidney from a deceased donor (62.2%), the primary cause for hospital admission
was infection (60.7%) and 57 (12.4%) individuals were diagnosed with acute
rejection (AR). The incidence of AKI was 82.3%: 31.9% stage 1, 29.3% stage 2 and
21.2% stage 3. Intensive care unit (ICU) admission (OR 8.90, 95% CI: 1.77-44.56 p
= 0.008), infection (OR 5.73, 95% CI: 2.61-12.56, p<0.001) and the use of
contrast media (OR 9.34, 95% CI: 2.04-42.70, p = 0.004) were the independent risk
factors for AKI development. The mortality rate was 2.1% and all patients who
died were diagnosed with AKI. Even after the exclusion of AR cases, at the end of
12 months, the individuals with AKI exhibited higher percent changes in
creatinine values when compared with individuals without AKI (9.1% vs. -4.3%;
p<0.001). According to KDIGO system, we found a high incidence of AKI among the
complications of renal transplantation. As in other scenarios, AKI was associated
with renal function loss at 1-year after the hospital discharge.
PMID- 26417951
TI - Complications after Radiofrequency Ablation of 233 Hepatic Tumors.
AB - OBJECTIVE: The only curative treatment for primary and secondary hepatic
malignancies is surgery and liver transplantation. Thus, the majority of the
patients are not candidates for resection, and there is a lack of organs. For
these reasons, alternative treatment modalities such as radiofrequency ablation
(RFA) are employed. The objective of this paper is to evaluate the incidence and
types of complications related to open and percutaneous RFA. METHOD: This is a
retrospective study of patients with hepatic malignancies treated by RFA. Tumor
size, location, numbers of nodules, approach, histology and associated procedures
were analyzed and correlated to complications. RESULTS: A total of 151 patients
with primary and secondary hepatic malignancies were included: 58 with
hepatocellular carcinoma (HCC), 68 with metastases from colorectal cancer and 25
with other types of tumors. Complications occurred in 24.5% of the patients,
mostly (58.9%) in those with HCC. Ascites was the most common complication,
followed by wound infection. The only two significant factors associated with
complications were the presence of HCC (p = 0.0087) and two or more lesions (p =
0.0323). The mortality rate was 0.69%. CONCLUSION: RFA is a safe technique, but
complications may occur and are multifactorial. Appropriate patient selection,
early complication recognition and adequate treatment are essential.
PMID- 26417952
TI - Real-time monitoring of rolling circle amplification using aggregation-induced
emission: applications in biological detection.
AB - We report that QATPE, an aggregation-induced emission-active tetraphenylethene
dye, can be used as a non-sequence-specific ssDNA probe for real-time monitoring
of all rolling circle amplification (RCA) reactions, thus making RCA more
suitable for biosensing applications.
PMID- 26417953
TI - The role of healthcare providers in the roll out of preexposure prophylaxis.
AB - PURPOSE OF REVIEW: To review the most recent studies assessing the preparedness
of healthcare practitioners to provide anti-HIV preexposure prophylaxis (PrEP)
and suggest areas for future implementation research. RECENT FINDINGS: As PrEP is
a biobehavioral intervention, healthcare providers are likely to play a critical
role in implementing PrEP in care settings. Studies suggest that many specialized
providers are aware of PrEP and support its provision as a public health
intervention, though knowledge and acceptance are less among generalists.
Therefore, utilization of PrEP by clinicians has been limited to a few early
adopters. Concerns about the efficacy and long-term safety of PrEP, and perceived
barriers to prescribing PrEP, could limit prescribing behaviors and intentions.
Resistance to performing routine HIV risk assessments by clinicians is an
additional barrier to implementing PrEP, although innovative tools to help
clinicians routinely perform risk assessments, are being developed. SUMMARY:
Interventions are needed to engage a broader array of healthcare providers in
PrEP provision. Utilizing a framework based on diffusion of innovation theory,
this review proposes strategies that can be implemented and evaluated to increase
PrEP prescribing by healthcare providers. If resources are invested in training
clinicians to provide PrEP, then these stakeholders could enhance the use of PrEP
as part of a prevention package by primary providers.
PMID- 26417954
TI - Tenofovir-based oral preexposure prophylaxis prevents HIV infection among women.
AB - PURPOSE OF REVIEW: Despite tremendous promise as a female-controlled HIV
prevention strategy, implementation of preexposure prophylaxis (PrEP) among women
has been limited, in part because of disparate efficacy results from randomized
trials in this population. This review synthesizes existing evidence regarding
PrEP efficacy for preventing HIV infection in women and considerations for
delivering PrEP to women. RECENT FINDINGS: In three efficacy trials, conducted
among men and women, tenofovir-based oral PrEP reduced HIV acquisition in
subgroups of women by 49-79% in intent-to-treat analyses, and by >85% when
accounting for PrEP adherence. Two trials did not demonstrate an HIV prevention
benefit from PrEP in women, but substantial evidence indicates those results were
compromised by very low adherence to the study medication. Qualitative research
has identified risk perception, stigma, and aspects of clinical trial
participation as influencing adherence to study medication. Pharmacokinetic
studies provide supporting evidence that PrEP offers HIV protection in women who
are adherent to the medication. SUMMARY: Tenofovir-based daily oral PrEP prevents
HIV acquisition in women. Offering PrEP as an HIV prevention option for women at
high risk of HIV acquisition is a public health imperative and opportunities to
evaluate implementation strategies for PrEP for women are needed.
PMID- 26417956
TI - DPP-4 inhibitors and risk of infections: a meta-analysis of randomized controlled
trials.
AB - BACKGROUND: To evaluate the risk of infections in the treatment of type 2
diabetes patients with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS: A
literature search was conducted through electronic databases. The inclusion
criteria included study duration of no less than 12 weeks developed in type 2
diabetes patients, the use of a randomized control group receiving a DPP-4
inhibitor and the availability of outcome data for infections. Out of 2181
studies, 74 studies were finally included. RESULTS: The risk of overall infection
for DPP-4 inhibitors treatment was comparable to placebo (odds ratio (OR) = 0.97,
95% confidence interval (CI), 0.91 to 1.04, p = 0.40), metformin treatment (OR =
1.22, 95% CI, 0.95 to 1.56, p = 0.12), sulphonylurea treatment (OR = 1.09, 0.93
to 1.29, p = 0.29), thiazolidinedione treatment (OR = 0.86, 95% CI, 0.65 to 1.14,
p = 0.29) and alpha glucosidase inhibitor treatment (OR = 1.03, 95% CI, 0.33 to
3.22, p = 0.96). When compared different DPP-4 inhibitors with placebo treatment,
risks of infections were comparable for alogliptin, linagliptin, sitagliptin,
saxagliptin and vildagliptin. Compared with placebo or active comparator
treatment, risks of infection in different systems for DPP-4 inhibitors were all
comparable. CONCLUSIONS: The overall risk of infections of DPP-4 inhibitor was
not increased compared with control groups.
PMID- 26417957
TI - A Randomized Controlled Trial of Positioning for Lumbar Puncture in Young
Infants.
AB - OBJECTIVE: The lateral and sitting positions are those most widely used to
perform lumbar puncture (LP) in infants. This study sought to compare LP success
rates by position. Secondary outcomes were successful LP on the first attempt and
rates of procedural complications. METHODS: Infants aged 1 to 90 days undergoing
LP in our pediatric emergency department between June 1, 2012 and October 31,
2013 were randomized to 1 position or the other. Successful LP was defined as
collection of cerebrospinal fluid with a red blood cell count of less than 10,000
cells/mm on either of the first 2 attempts. Electronic medical records were
reviewed for patient information, cerebrospinal fluid results, and procedural
complications. Providers completed a questionnaire detailing their previous LP
experience and technique. Primary results were analyzed using the intention-to
treat principle. RESULTS: We enrolled 168 infants. Of 167 with data eligible for
analysis, 82 (49%) were randomized to the lateral position. There was no
statistically significant difference in LP success rate between the lateral (77%,
63/82) and sitting (72%, 61/85) positions (difference, 5.1%; 95% confidence
interval, -8.2%-18.3%). There were no significant differences in success on the
first LP attempt or the rates of procedural complications. CONCLUSIONS: Among
infants 1 to 90 days of age, this study found no difference in LP success between
the lateral and sitting positions.
PMID- 26417955
TI - Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1
and Atazanavir Prescribing.
AB - The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine
diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the
glucuronidation and elimination of bilirubin. Resultant indirect
hyperbilirubinemia with jaundice can cause premature discontinuation of
atazanavir. Risk for bilirubin-related discontinuation is highest among
individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37).
We summarize published literature that supports this association and provide
recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates
at www.pharmgkb.org).
PMID- 26417958
TI - Determinants of Pediatric Psychiatry Length of Stay in 2 Urban Emergency
Departments.
AB - OBJECTIVES: Pediatric mental illness poses a significant burden with an overall
prevalence of approximately 10%. Increasingly, children with mental disorders
seek care in the emergency department (ED). However, the ED is not an ideal
setting. Pediatric mental health patients receive limited treatment and
experience significantly longer length of stay (LOS) than other patients seen in
the ED. This study examines patient and hospital factors associated with LOS and
prolonged LOS (PLOS). METHODS: This is a retrospective chart review of patients
between the ages of 3 and 17 presenting at 2 participating urban EDs with a
psychiatric diagnosis from May 2010 to May 2012. RESULTS: This study includes 939
patients with an average age of 14.1 years and a median LOS of 295 minutes. The
diagnosis was the strongest predictor of LOS and PLOS. Patients with a psychotic
disorder or suicide attempt or ideation experienced a longer LOS, 35% and 55%
increases, respectively, and an increased odds of PLOS (odds ratio, 3.07 and
8.36, respectively). Patient sex, previous history of self-harm, and the daily
census were associated with both a longer LOS and PLOS. Ethnicity, site of
admission, and year of admission were only associated with LOS. CONCLUSIONS:
Diagnosis-specific management factors are the primary determinant of LOS.
However, some patient characteristics and hospital operational factors are also
associated with LOS. Organizational reforms and an evaluation of the required
human and material resources are necessary to improve access to and availability
of pediatric mental health care.
PMID- 26417959
TI - Bullying and Suicide Risk Among Pediatric Emergency Department Patients.
AB - OBJECTIVES: This study aimed to describe the association between recent bullying
victimization and risk of suicide among pediatric emergency department (ED)
patients. METHODS: Patients presenting to 1 of 3 different urban pediatric EDs
with either medical/surgical or psychiatric chief complaints completed structured
interviews as part of a study to develop a suicide risk screening instrument, the
Ask Suicide-Screening Questions. Seventeen candidate items and the criterion
reference Suicidal Ideation Questionnaire were administered to patients ages 10
to 21 years. Bullying victimization was assessed by a single candidate item ("In
the past few weeks, have you been bullied or picked on so much that you felt like
you couldn't stand it anymore?"). RESULTS: A total of 524 patients completed the
interview (34.4% psychiatric chief complaints; 56.9% female; 50.4% white, non
Hispanic; mean [SD] age, 15.2 [2.6] years). Sixty patients (11.5%) reported
recent bullying victimization, and of these, 33 (55.0%) screened positive for
suicide risk on the Ask Suicide-Screening Questions or the previously validated
Suicidal Ideation Questionnaire. After controlling for demographic and clinical
variables, including a history of depression and drug use, the odds of screening
positive for suicide risk were significantly greater in patients who reported
recent bullying victimization (adjusted odds ratio, 3.19; 95% confidence
interval, 1.66-6.11). After stratification by chief complaint, this association
persisted for medical/surgical patients but not for psychiatric patients.
CONCLUSIONS: Recent bullying victimization was associated with increased odds of
screening positive for elevated suicide risk among pediatric ED patients
presenting with medical/surgical complaints. Understanding this important
correlate of suicide risk in pediatric ED patients may help inform ED-based
suicide prevention interventions.
PMID- 26417961
TI - A Cationic MOF with High Uptake and Selectivity for CO2 due to Multiple CO2
Philic Sites.
AB - The reaction of N-rich pyrazinyl triazolyl carboxyl ligand 3-(4-carboxylbenzene)
5-(2-pyrazinyl)-1H-1,2,4-triazole (H2 cbptz) with MnCl2 afforded 3D cationic
metal-organic framework (MOF) [Mn2 (Hcbptz)2 (Cl)(H2 O)]Cl?DMF?0.5 CH3 CN (1),
which has an unusual (3,4)-connected 3,4T1 topology and 1D channels composed of
cavities. MOF 1 has a very polar framework that contains exposed metal sites,
uncoordinated N atoms, narrow channels, and Cl(-) basic sites, which lead to not
only high CO2 uptake, but also remarkably selective adsorption of CO2 over N2 and
CH4 at 298-333 K. The multiple CO2 -philic sites were identified by grand
canonical Monte Carlo simulations. Moreover, 1 shows excellent stability in
natural air environment. These advantages make 1 a very promising candidate in
post-combustion CO2 capture, natural-gas upgrading, and landfill gas-purification
processes.
PMID- 26417962
TI - Molecular basis of alcoholic fatty liver disease: From incidence to treatment.
AB - Alcoholic liver diseases have complex and multiple pathogenic mechanisms but
still no effective treatment. Steatosis or alcoholic fatty liver disease (AFLD)
has a widespread incidence and is the first step in the progression to more
severe stages of alcoholic liver disease, with concomitant increases in morbidity
and mortality rates. The ways in which this progression occurs and why some
individuals are susceptible are still unanswered scientific questions. Research
with animal models and clinical evidence have shown that it is a multifactorial
disease that involves interactions between lipid metabolism, inflammation, the
immune response and oxidative stress. Each of these pathways provides a better
understanding of the pathogenesis of AFLD and contributes to the development of
therapeutic strategies. This review emphasizes the importance of research on
alcoholic steatosis based on incidence data, key pathogenic mechanisms and
therapeutic interventions, and discusses perspectives on the progression of this
disease.
PMID- 26417963
TI - Nonidentical twins: Comparison of frequentist and Bayesian lasso for Cox models.
AB - One important task in translational cancer research is the search for new
prognostic biomarkers to improve survival prognosis for patients. The use of high
throughput technologies allows simultaneous measurement of genome-wide gene
expression or other genomic data for all patients in a clinical trial. Penalized
likelihood methods such as lasso regression can be applied to such high
dimensional data, where the number of (genomic) covariables is usually much
larger than the sample size. There is a connection between the lasso and the
Bayesian regression model with independent Laplace priors on the regression
parameters, and understanding this connection has been useful for understanding
the properties of lasso estimates in linear models (e.g. Park and Casella, 2008).
In this paper, we study the lasso in the frequentist and Bayesian frameworks in
the context of Cox models. For the Bayesian lasso we extend the approach by Lee
et al. (2011). In particular, we impose the lasso penalty only on the genome
features, but not on relevant clinical covariates, to allow the mandatory
inclusion of important established factors. We investigate the models in high-
and low-dimensional simulation settings and in an application to chronic
lymphocytic leukemia.
PMID- 26417964
TI - Impact of Fighting on Antibody Response to Hepatitis B Virus Vaccine in Mice.
AB - Antibody responses to vaccines can be influenced by various behavioral and
psychosocial factors. Few reports exist on the impact of fighting on antibody
response to vaccines. This study unexpectedly found that fighting could
significantly enhance antibody production in male mice immunized with hepatitis B
virus (HBV) vaccines. To confirm the finding, a mouse-fighting model was
established in which it was observed that only intense fighting, not mild
fighting, enhanced the antibody response to HBV surface antigen in male mice, and
that the frequency of fighting and active attacks during fighting showed no
obvious relationship with the antibody levels in the male mice that experienced
fighting. In addition, fighting can cause significant upregulation of CD80 in
CD11c(+) cells in the spleen of male mice. These data suggest that fighting could
influence the humoral immune response in individuals immunized with vaccines or
infected with microbes.
PMID- 26417966
TI - Understanding the cancer cell phenotype beyond the limitations of current omics
analyses.
AB - Efforts to understand the mechanistic principles driving cancer metabolism and
proliferation have been lately governed by genomic, transcriptomic and proteomic
studies. This paper analyzes the caveats of these approaches. As molecular
biology's central dogma proposes a unidirectional flux of information from genes
to mRNA to proteins, it has frequently been assumed that monitoring the changes
in the gene sequences and in mRNA and protein contents is sufficient to explain
complex cellular processes. Such a stance commonly disregards that post
translational modifications can alter the protein function/activity and also that
regulatory mechanisms enter into action, to coordinate the protein activities of
pathways/cellular processes, in order to keep the cellular homeostasis. Hence,
the actual protein activities (as enzymes/transporters/receptors) and their
regulatory mechanisms ultimately dictate the final outcomes of a pathway/cellular
process. In this regard, it is here documented that the mRNA levels of many
metabolic enzymes and transcriptional factors have no correlation with the
respective protein contents and activities. The validity of current clinical mRNA
based tests and proposed metabolite biomarkers for cancer detection/prognosis is
also discussed. Therefore, it is proposed that, to achieve a thorough
understanding of the modifications undergone by proliferating cancer cells, it is
mandatory to experimentally analyze the cellular processes at the functional
level. This could be achieved (a) locally, by examining the actual protein
activities in the cell and their kinetic properties (or at least kinetically
characterize the most controlling steps of the pathway/cellular process); (b)
systemically, by analyzing the main fluxes of the pathway/cellular process, and
how they are modulated by metabolites, all which should contribute to
comprehending the regulatory mechanisms that have been altered in cancer cells.
By adopting a more holistic approach it may become possible to improve the design
of therapeutic strategies that would target cancer cells more specifically.
PMID- 26417968
TI - Palliation of unresectable cholangiocarcinoma: can we do more than merely drain?
PMID- 26417965
TI - Emergency Hospital Care for Exacerbation of COPD: Is Inhaled Maintenance Therapy
Modified?
AB - BACKGROUND: The impact of hospital emergency care and inward admission for acute
exacerbations of COPD on inhaled maintenance treatment is not well known.
OBJECTIVE: Therefore, we evaluated the impact of short-stay emergency hospital
care and inward admission for acute exacerbation of COPD (eCOPD) on inhaled
maintenance treatment prescribed at discharge. DESIGN: Prospective observational
cohort study of patients presenting with eCOPD at emergency departments in 16
hospitals of the Spanish healthcare system. The ethics committee at each hospital
approved the study and patients provided an informed consent before inclusion. We
classified the patients according to the severity of COPD: mild/moderate (FEV1 >=
50% predicted) or severe/very severe (FEV1 < 50% predicted) and need of inward
hospitalisation. We analysed changes to maintenance treatment on discharge
according to GOLD strategy. RESULTS: 1559 patients, 65% required hospitalisation.
The most common maintenance treatment was inhaled corticoids (ICS) (80.9%)
followed by long-acting beta-agonists (LABA) (75.4%). The most common combination
was triple therapy (LABA+ LAMA+ICS) (56.2%) followed by LABA+ICS dual therapy
(18.2%) regardless of the severity of COPD. In more than 60% of patients
treatment was not changed at discharge. The most common change in treatment was a
reduction when discharge was from emergency care and an increase after
hospitalisation (-21.6% and +19.5% in severe/very severe COPD, respectively).
CONCLUSIONS: Emergency hospital care for eCOPD does not usually induce changes in
inhaled maintenance treatment for COPD regardless of the duration of the hospital
stay.
PMID- 26417967
TI - Epigenetic Control of Apolipoprotein E Expression Mediates Gender-Specific
Hematopoietic Regulation.
AB - Epigenetic alterations play a central role in the control of normal and malignant
blood cell development. We demonstrate here that expression of a truncated DNA
methyltransferase 3B isoform DNMT3B7, which has been shown to alter cellular
epigenetic patterns, decreases the overall number of hematopoietic stem and
progenitor cells (HSPCs), and markedly diminishes blood cell reconstitution
within the female hormonal microenvironment. Gene expression profiling of HSPCs
isolated from DNMT3B7 transgenic embryos identified Apolipoprotein E (Apoe) as
overexpressed. The CpG island controlling Apoe expression had lower levels of
modified cytosines in DNMT3B7 transgenic HSPCs, corresponding with the observed
increase in gene expression. Furthermore, we observed that spleens and bone
marrows of female mice transplanted with DNMT3B7 transgenic HSPCs express very
high levels of Apoe. Finally, the introduction of Apoe-overexpressing HSPCs into
male recipients decreased bone marrow engraftment, recapitulating our original
observations in female recipients. Our work reveals a dynamic interplay between
the intrinsic epigenetic changes in HSPCs and extrinsic endocrine factors acting
on these cells to regulate the efficiency of HSPC engraftment and reconstitution.
We have identified a novel mechanism by which gender-specific hormones modulate
HSPC function, which could serve as a target for augmenting hematopoiesis in
cases with limited HSC functionality.
PMID- 26417969
TI - Farewell to the cap or is there still an indication?
PMID- 26417970
TI - Show me how you remove small polyps and I'll tell you who you are.
PMID- 26417971
TI - Hybrid biliary interventions for Roux-en-Y anatomy.
PMID- 26417972
TI - Reply to Kobiela et al.
PMID- 26417973
TI - Reply to Kobiela et al.
PMID- 26417974
TI - Water exchange versus carbon dioxide insufflation in unsedated colonoscopy: less
is more.
PMID- 26417975
TI - Reply to Ishaq et al.
PMID- 26417978
TI - [Not Available].
PMID- 26417979
TI - [Not Available].
PMID- 26417981
TI - Video comment on Saurabh Mukewar et al.
PMID- 26417980
TI - Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage:
European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
AB - This Guideline is an official statement of the European Society of
Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of
nonvariceal upper gastrointestinal hemorrhage (NVUGIH). Main Recommendations MR1.
ESGE recommends immediate assessment of hemodynamic status in patients who
present with acute upper gastrointestinal hemorrhage (UGIH), with prompt
intravascular volume replacement initially using crystalloid fluids if
hemodynamic instability exists (strong recommendation, moderate quality
evidence). MR2. ESGE recommends a restrictive red blood cell transfusion strategy
that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target
hemoglobin should be considered in patients with significant co-morbidity (e. g.,
ischemic cardiovascular disease) (strong recommendation, moderate quality
evidence). MR3. ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for
pre-endoscopy risk stratification. Outpatients determined to be at very low risk,
based upon a GBS score of 0 - 1, do not require early endoscopy nor hospital
admission. Discharged patients should be informed of the risk of recurrent
bleeding and be advised to maintain contact with the discharging hospital (strong
recommendation, moderate quality evidence). MR4. ESGE recommends initiating high
dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by
continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute
UGIH awaiting upper endoscopy. However, PPI infusion should not delay the
performance of early endoscopy (strong recommendation, high quality evidence).
MR5. ESGE does not recommend the routine use of nasogastric or orogastric
aspiration/lavage in patients presenting with acute UGIH (strong recommendation,
moderate quality evidence). MR6. ESGE recommends intravenous erythromycin (single
dose, 250 mg given 30 - 120 minutes prior to upper gastrointestinal [GI]
endoscopy) in patients with clinically severe or ongoing active UGIH. In selected
patients, pre-endoscopic infusion of erythromycin significantly improves
endoscopic visualization, reduces the need for second-look endoscopy, decreases
the number of units of blood transfused, and reduces duration of hospital stay
(strong recommendation, high quality evidence). MR7. Following hemodynamic
resuscitation, ESGE recommends early (<= 24 hours) upper GI endoscopy. Very early
(< 12 hours) upper GI endoscopy may be considered in patients with high risk
clinical features, namely: hemodynamic instability (tachycardia, hypotension)
that persists despite ongoing attempts at volume resuscitation; in-hospital
bloody emesis/nasogastric aspirate; or contraindication to the interruption of
anticoagulation (strong recommendation, moderate quality evidence). MR8. ESGE
recommends that peptic ulcers with spurting or oozing bleeding (Forrest
classification Ia and Ib, respectively) or with a nonbleeding visible vessel
(Forrest classification IIa) receive endoscopic hemostasis because these lesions
are at high risk for persistent bleeding or rebleeding (strong recommendation,
high quality evidence). MR9. ESGE recommends that peptic ulcers with an adherent
clot (Forrest classification IIb) be considered for endoscopic clot removal. Once
the clot is removed, any identified underlying active bleeding (Forrest
classification Ia or Ib) or nonbleeding visible vessel (Forrest classification
IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality
evidence). MR10. In patients with peptic ulcers having a flat pigmented spot
(Forrest classification IIc) or clean base (Forrest classification III), ESGE
does not recommend endoscopic hemostasis as these stigmata present a low risk of
recurrent bleeding. In selected clinical settings, these patients may be
discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong
recommendation, moderate quality evidence). MR11. ESGE recommends that
epinephrine injection therapy not be used as endoscopic monotherapy. If used, it
should be combined with a second endoscopic hemostasis modality (strong
recommendation, high quality evidence). MR12. ESGE recommends PPI therapy for
patients who receive endoscopic hemostasis and for patients with adherent clot
not receiving endoscopic hemostasis. PPI therapy should be high dose and
administered as an intravenous bolus followed by continuous infusion (80 mg then
8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality
evidence). MR13. ESGE does not recommend routine second-look endoscopy as part of
the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH).
However, in patients with clinical evidence of rebleeding following successful
initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with
hemostasis if indicated. In the case of failure of this second attempt at
hemostasis, transcatheter angiographic embolization (TAE) or surgery should be
considered (strong recommendation, high quality evidence). MR14. In patients with
NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence
of Helicobacter pylori in the acute setting with initiation of appropriate
antibiotic therapy when H. pylori is detected. Re-testing for H. pylori should be
performed in those patients with a negative test in the acute setting.
Documentation of successful H. pylori eradication is recommended (strong
recommendation, high quality evidence). MR15. In patients receiving low dose
aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer
bleeding, ESGE recommends aspirin be resumed immediately following index
endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with
high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by
day 3 after index endoscopy is recommended, provided that adequate hemostasis has
been established (strong recommendation, moderate quality evidence).
PMID- 26417982
TI - Video comment on Mohammad Yaghoobi et al.
PMID- 26417983
TI - Video comment on Roger G. Blanks et al.
PMID- 26417984
TI - Mesh size analysis of cellulose nanofibril hydrogels using solute exclusion and
PFG-NMR spectroscopy.
AB - The pore structure of TEMPO-mediated oxidized CNF hydrogels, chemically cross
linked with water-soluble diamines, is studied. A solute exclusion method and
pulsed-field-gradient NMR are used to estimate the mesh size distribution in the
gel network in its hydrated state. Dextran fractions with the nominal molecular
weights in the range of 10-2000 kDa are used as probes. The results show a
nonuniform network structure, consisting of a group of large openings that
contain ~50% of water, and regions with a more compact structure and smaller mesh
units that restrict the diffusivity of the dextran molecules. A biexponential
model is proposed for the NMR echo amplitude decay due to the probe diffusion
into the gel network. A typical single exponential model does not fit the
experimental data when the probe molecular size is comparable to the network mesh
size. The results obtained with NMR, using the proposed biexponential model, are
in very good agreement with those determined with solute exclusion. Precise mesh
size estimation with solute exclusion using pore models is subject to
restrictions, and vary with the assumed pore geometry. The average mesh size
obtained using a spherical pore model, ~35 nm, in the compact regions of the
hydrogel, is in good agreement with the theoretical value in a network of rodlike
particles. Neglecting the wall effects leads to underestimation of the mesh size
with both techniques.
PMID- 26417985
TI - Alkali-Metal-Mediated Magnesiations of an N-Heterocyclic Carbene: Normal,
Abnormal, and "Paranormal" Reactivity in a Single Tritopic Molecule.
AB - Herein the sodium alkylmagnesium amide [Na4Mg2(TMP)6(nBu)2] (TMP=2,2,6,6
tetramethylpiperidide), a template base as its deprotonating action is dictated
primarily by its 12 atom ring structure, is studied with the common N
heterocyclic carbene (NHC) IPr [1,3-bis(2,6-diisopropylphenyl)imidazol-2
ylidene]. Remarkably, magnesiation of IPr occurs at the para-position of an aryl
substituent, sodiation occurs at the abnormal C4 position, and a dative bond
occurs between normal C2 and sodium, all within a 20 atom ring structure
accommodating two IPr(2-). Studies with different K/Mg and Na/Mg bimetallic bases
led to two other magnesiated NHC structures containing two or three IPr(-)
monoanions bound to Mg through abnormal C4 sites. Synergistic in that
magnesiation can only work through alkali-metal mediation, these reactions add
magnesium to the small cartel of metals capable of directly metalating a NHC.
PMID- 26417986
TI - Reply.
PMID- 26417988
TI - Magnetic resonance elastography of the brain: An in silico study to determine the
influence of cranial anatomy.
AB - PURPOSE: Magnetic resonance elastography (MRE) of the brain has demonstrated
potential as a biomarker of neurodegenerative disease such as dementia but
requires further evaluation. Cranial anatomical features such as the falx cerebri
and tentorium cerebelli membranes may influence MRE measurements through wave
reflection and interference and tissue heterogeneity at their boundaries. We
sought to determine the influence of these effects via simulation. METHODS: MRE
associated mechanical stimulation of the brain was simulated using steady state
harmonic finite element analysis. Simulations of geometrical models and
anthropomorphic brain models derived from anatomical MRI data of healthy
individuals were compared. Constitutive parameters were taken from MRE
measurements for healthy brain. Viscoelastic moduli were reconstructed from the
simulated displacement fields and compared with ground truth. RESULTS:
Interference patterns from reflections and heterogeneity resulted in artifacts in
the reconstructions of viscoelastic moduli. Artifacts typically occurred in the
vicinity of boundaries between different tissues within the cranium, with a
magnitude of 10%-20%. CONCLUSION: Given that MRE studies for neurodegenerative
disease have reported only marginal variations in brain elasticity between
controls and patients (e.g., 7% for Alzheimer's disease), the predicted errors
are a potential confound to the development of MRE as a biomarker of dementia and
other neurodegenerative diseases. Magn Reson Med 76:645-662, 2016. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26417987
TI - Biomodulatory metronomic therapy in stage IV melanoma is well-tolerated and may
induce prolonged progression-free survival, a phase I trial.
PMID- 26417989
TI - Genetic Variation of Sclerotinia sclerotiorum from Multiple Crops in the North
Central United States.
AB - Sclerotinia sclerotiorum is an important pathogen of numerous crops in the North
Central region of the United States. The objective of this study was to examine
the genetic diversity of 145 isolates of the pathogen from multiple hosts in the
region. Mycelial compatibility groups (MCG) and microsatellite haplotypes were
determined and analyzed for standard estimates of population genetic diversity
and the importance of host and distance for genetic variation was examined. MCG
tests indicated there were 49 different MCGs in the population and 52 unique
microsatellite haplotypes were identified. There was an association between MCG
and haplotype such that isolates belonging to the same MCG either shared
identical haplotypes or differed at no more than 2 of the 12 polymorphic loci.
For the majority of isolates, there was a one-to-one correspondence between MCG
and haplotype. Eleven MCGs shared haplotypes. A single haplotype was found to be
prevalent throughout the region. The majority of genetic variation in the isolate
collection was found within rather than among host crops, suggesting little
genetic divergence of S. sclerotiorum among hosts. There was only weak evidence
of isolation by distance. Pairwise population comparisons among isolates from
canola, dry bean, soybean and sunflower suggested that gene flow between host
populations is more common for some crops than others. Analysis of linkage
disequilibrium in the isolates from the four major crops indicated primarily
clonal reproduction, but also evidence of genetic recombination for isolates from
canola and sunflower. Accordingly, genetic diversity was highest for populations
from canola and sunflower. Distribution of microsatellite haplotypes across the
study region strongly suggest that specific haplotypes of S. sclerotiorum are
often found on multiple crops, movement of individual haplotypes among crops is
common and host identity is not a barrier to gene flow for S. sclerotiorum in the
north central United States.
PMID- 26417990
TI - Preterm Cord Blood Contains a Higher Proportion of Immature Hematopoietic
Progenitors Compared to Term Samples.
AB - BACKGROUND: Cord blood contains high number of hematopoietic cells that after
birth disappear. In this paper we have studied the functional properties of the
umbilical cord blood progenitor cells collected from term and preterm neonates to
establish whether quantitative and/or qualitative differences exist between the
two groups. METHODS AND RESULTS: Our results indicate that the percentage of
total CD34+ cells was significantly higher in preterm infants compared to full
term: 0.61% (range 0.15-4.8) vs 0.3% (0.032-2.23) p = 0.0001 and in neonates <32
weeks of gestational age (GA) compared to those >=32 wks GA: 0.95% (range 0.18
4.8) and 0.36% (0.15-3.2) respectively p = 0.0025. The majority of CD34+ cells co
expressed CD71 antigen (p<0.05 preterm vs term) and grew in vitro large BFU-E,
mostly in the second generation. The subpopulations CD34+CD38- and CD34+CD45-
resulted more represented in preterm samples compared to term, conversely, Side
Population (SP) did not show any difference between the two group. The absolute
number of preterm colonies (CFCs/10microL) resulted higher compared to term (p =
0.004) and these progenitors were able to grow until the third generation
maintaining an higher proportion of CD34+ cells (p = 0.0017). The number of
colony also inversely correlated with the gestational age (Pearson r = -0.3001
p<0.0168). CONCLUSIONS: We found no differences in the isolation and expansion
capacity of Endothelial Colony Forming Cells (ECFCs) from cord blood of term and
preterm neonates: both groups grew in vitro large number of endothelial cells
until the third generation and showed a transitional phenotype between
mesenchymal stem cells and endothelial progenitors (CD73, CD31, CD34 and
CD144)The presence, in the cord blood of preterm babies, of high number of
immature hematopoietic progenitors and endothelial/mesenchymal stem cells with
high proliferative potential makes this tissue an important source of cells for
developing new cells therapies.
PMID- 26417991
TI - Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering
IgA Class Switching Recombination through the TLR3-BAFF Axis.
AB - BACKGROUND: Immunoglobulin class-switch recombination (CSR) is crucial for the
expression of IgA, and it plays a vital role in the physiopathology of IgA
nephropathy (IgAN). The aim of the study is to investigate the effect of
polyriboinosinic:polyribocytidylic acid (poly(I:C)) in modulating toll-like
receptor (TLR) 3-B-cell-activating factor belonging to the TNF family (BAFF) axis
activation, which in turn promotes IgA CSR of IgAN patients and the IgAN rat
model. METHODS: Blood samples and tonsillar tissue specimens were obtained from
24 patients with IgAN and 26 patients with chronic tonsillitis as control. We
also used the IgAN rat model to investigate the relationship between viral
infection and IgA CSR. RESULTS: Immunohistochemical and ELISA western blotting
examination revealed that the TLR3/BAFF axis is activated in IgAN patients when
compared to controls. Synthetic double-stranded RNA poly(I:C) stimulation
upregulates the TACI/TLR3/TRIF/TRAF6 expression and promotes IgA CSR and BAFF
productions in tonsil mononuclear cells. TLR3 or BAFF siRNA decreases IgA
expression. In IgAN rat models, TLR3/BAFF signaling was highly activated. With
200 MUg poly(I:C) sodium salt into the left naris for 8 weeks, IgA was highly
deposited on glomeruli. It also revealed that poly(I:C) activated TLR3/BAFF axis
and IgA CSR in vivo. CONCLUSION: These data points toward the role of TLR3/BAFF
axis in IgA CSR of IgAN, and the data also support the notion that mucosal
immunization with virus infection results in impaired mucosal and systemic IgA
responses.
PMID- 26417992
TI - Impact of Frontal Lobe Function and Behavioral Changes on Health-Related Quality
of Life in Patients with Parkinson's Disease: A Cross-Sectional Study from
Southwest China.
AB - BACKGROUND: Cognitive impairment may negatively impact the health-related quality
of life (HRQoL) in patients with Parkinson's disease (PD). However, information
on the effects of frontal lobe function and behavior changes on the HRQoL of the
Chinese PD population is limited. Studies on the associations among frontal lobe
function, behavioral changes and the HRQoL may help optimize the treatment and
improve the HRQoL of PD patients. METHODS: A total of 309 PD patients were
evaluated using the Frontal Assessment Battery, the Frontal Behavioral Inventory
(FBI) and the PD Questionnaire 39-item version (PDQ-39). RESULTS: Patients with
worse frontal lobe function were older (p < 0.001), had longer disease durations
(p = 0.002), higher Unified Parkinson's Disease Rating Scale part III (UPDRS-III)
scores (p < 0.001) and higher Hoehn and Yahr (H-Y) stages (p = 0.001), and
exhibited significantly higher PDQ-39 summary index (SI; p = 0.001) compared with
those who had better frontal lobe function. In addition, the disease duration (p
= 0.008), UPDRS-III scores (p < 0.001), H-Y stage (p < 0.001), PDQ-39 SI and
scores for each domain of the PDQ-39 (p < 0.001) were higher as the severity of
frontal behavioral changes increased. The total FBI score (p < 0.001) was
positively correlated with the PDQ-39 SI. CONCLUSIONS: Frontal behavioral changes
were closely associated with poor HRQoL in Chinese PD patients.
PMID- 26417994
TI - Satellite Based Assessment of Hydroclimatic Conditions Related to Cholera in
Zimbabwe.
AB - INTRODUCTION: Cholera, an infectious diarrheal disease, has been shown to be
associated with large scale hydroclimatic processes. The sudden and sporadic
occurrence of epidemic cholera is linked with high mortality rates, in part, due
to uncertainty in timing and location of outbreaks. Improved understanding of the
relationship between pathogenic abundance and climatic processes allows
prediction of disease outbreak to be an achievable goal. In this study, we show
association of large scale hydroclimatic processes with the cholera epidemic in
Zimbabwe reported to have begun in Chitungwiza, a city in Mashonaland East
province, in August, 2008. PRINCIPAL FINDINGS: Climatic factors in the region
were found to be associated with triggering cholera outbreak and are shown to be
related to anomalies of temperature and precipitation, validating the hypothesis
that poor conditions of sanitation, coupled with elevated temperatures, and
followed by heavy rainfall can initiate outbreaks of cholera. Spatial estimation
by satellite of precipitation and global gridded air temperature captured
sensitivities in hydroclimatic conditions that permitted identification of the
location in the region where the disease outbreak began. DISCUSSION: Satellite
derived hydroclimatic processes can be used to capture environmental conditions
related to epidemic cholera, as occurred in Zimbabwe, thereby providing an early
warning system. Since cholera cannot be eradicated because the causative agent,
Vibrio cholerae, is autochthonous to the aquatic environment, prediction of
conditions favorable for its growth and estimation of risks of triggering the
disease in a given population can be used to alert responders, potentially
decreasing infection and saving lives.
PMID- 26417995
TI - Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF
beta1/Smad3/HDAC Signaling Pathway by Deriving miR-675.
AB - Long noncoding RNAs (lncRNAs) are emerging as important regulatory molecules at
the transcriptional and post-transcriptional levels and may play essential roles
in the differentiation of human bone marrow mesenchymal stem cell (hMSC).
However, their roles and functions remain unclear. Here, we showed that lncRNA
H19 was significantly upregulated after the induction of osteoblast
differentiation. Overexpression of H19 promoted osteogenic differentiation of
hMSCs in vitro and enhanced heterotopic bone formation in vivo, whereas knockdown
of H19 inhibited these effects. Subsequently, we found that miR-675, encoded by
exon1 of H19, promoted osteoblast differentiation of hMSCs and was partially
responsible for the pro-osteogenic effect of H19. Investigating the underlying
mechanism, we demonstrated that H19/miR-675 inhibited mRNA and protein expression
of transforming growth factor-beta1 (TGF-beta1). The downregulation of TGF-beta1
subsequently inhibited phosphorylation of Smad3. Meanwhile, H19/miR-675
downregulated the mRNA and protein levels of histone deacetylase (HDAC) 4/5, and
thus increased osteoblast marker gene expression. Taken together, our results
demonstrated that the novel pathway H19/miR-675/TGF-beta1/Smad3/HDAC regulates
osteogenic differentiation of hMSCs and may serve as a potential target for
enhancing bone formation in vivo.
PMID- 26417996
TI - An Advanced Sodium-Ion Battery Composed of Carbon Coated Na3V2(PO4)3 in a Porous
Graphene Network.
AB - A 3D hierarchical meso- and macroporous Na3V2(PO4)3-based hybrid cathode with
connected Na ion/electron pathways is developed for ultra-fast charge and
discharge sodium-ion batteries. It delivers an excellent rate capability (e.g.,
86 mA h g(-1) at 100 C) and outstanding cycling stability (e.g., 64% retention
after 10,000 cycles at 100 C), indicating its superiority in practical
applications.
PMID- 26417997
TI - Dysregulation of host cellular genes targeted by human papillomavirus (HPV)
integration contributes to HPV-related cervical carcinogenesis.
AB - Integration of human papillomavirus (HPV) viral DNA into the human genome has
been postulated as an important etiological event during cervical carcinogenesis.
Several recent reports suggested a possible role for such integration-targeted
cellular genes (ITGs) in cervical carcinogenesis. Therefore, a comprehensive
analysis of HPV integration events was undertaken using data collected from 14
publications, with 499 integration loci on human chromosomes included. It
revealed that HPV DNA preferred to integrate into intragenic regions and gene
dense regions of human chromosomes. Intriguingly, the host cellular genes nearby
the integration sites were found to be more transcriptionally active compared
with control. Furthermore, analysis of the integration sites in the human genome
revealed that there were several integration hotspots although all chromosomes
were represented. The ITGs identified were found to be enriched in tumor-related
terms and pathways using gene ontology and KEGG analysis. In line with this,
three of six ITGs tested were found aberrantly expressed in cervical cancer
tissues. Among them, it was demonstrated for the first time that MPPED2 could
induce HeLa cell and SiHa cell G1/S transition block and cell proliferation
retardation. Moreover, "knocking out" the integrated HPV fragment in HeLa cell
line decreased expression of MYC located ~500 kb downstream of the integration
site, which provided the first experimental evidence supporting the hypothesis
that integrated HPV fragment influence MYC expression via long distance chromatin
interaction. Overall, the results of this comprehensive analysis implicated that
dysregulation of ITGs caused by viral integration as possibly having an
etiological involvement in cervical carcinogenesis.
PMID- 26417998
TI - A prospective, randomized, double-blind comparison of an ablative fractional 2940
nm erbium-doped yttrium aluminum garnet laser with a nonablative fractional 1550
nm erbium-doped glass laser for the treatment of photoaged Asian skin.
AB - BACKGROUND: As compared with ablative fractional CO2 laser, ablative fractional
erbium-doped yttrium aluminum garnet (Er:YAG) laser is considered to be a more
suitable treatment option for photoaged skin in Asians due to the lower incidence
of postinflammatory hyperpigmentation. OBJECTIVE: To compare the efficacy and
safety of ablative fractional Er:YAG laser (ablative fractional resurfacing
[AFR]) and nonablative fractional 1550-nm Er:glass laser (non-AFR [NAFR]) in the
treatment of photoaging. METHODS: This was a prospective, randomized, double
blinded comparative study. In three sessions, at four-week intervals, 19 patients
received Er:YAG AFR, and 15 patients received Er:glass NAFR. Pigmentation, uneven
tone/erythema, wrinkles and overall features of photoaging were scored. Patient
satisfaction, adverse effects and pain scores were recorded. Melanin and erythema
indexes were measured. RESULTS: Reductions in pigmentation and uneven
tone/erythema scores were significantly greater after Er:YAG AFR, while wrinkle
score reduction was significantly greater after Er:glass NAFR. Physician and
patient assessments for the overall features showed greater improvement in the
Er:glass NAFR. Treatment-related pain or adverse events were less in the Er:YAG
AFR. CONCLUSION: Both Er:YAG AFR and Er:glass NAFR are effective and safe and
could be used in a complementary manner for treating photoaged Asian skin.
PMID- 26417999
TI - Tracking Time Evolution of Collective Attention Clusters in Twitter: Time
Evolving Nonnegative Matrix Factorisation.
AB - Micro-blogging services, such as Twitter, offer opportunities to analyse user
behaviour. Discovering and distinguishing behavioural patterns in micro-blogging
services is valuable. However, it is difficult and challenging to distinguish
users, and to track the temporal development of collective attention within
distinct user groups in Twitter. In this paper, we formulate this problem as
tracking matrices decomposed by Nonnegative Matrix Factorisation for time
sequential matrix data, and propose a novel extension of Nonnegative Matrix
Factorisation, which we refer to as Time Evolving Nonnegative Matrix
Factorisation (TENMF). In our method, we describe users and words posted in some
time interval by a matrix, and use several matrices as time-sequential data.
Subsequently, we apply Time Evolving Nonnegative Matrix Factorisation to these
time-sequential matrices. TENMF can decompose time-sequential matrices, and can
track the connection among decomposed matrices, whereas previous NMF decomposes a
matrix into two lower dimension matrices arbitrarily, which might lose the time
sequential connection. Our proposed method has an adequately good performance on
artificial data. Moreover, we present several results and insights from
experiments using real data from Twitter.
PMID- 26418000
TI - Influence of Cervical Muscle Fatigue on Musculo-Tendinous Stiffness of the Head
Neck Segment during Cervical Flexion.
AB - AIM: The aim of this study is to determine if the fatigue of cervical muscles has
a significant influence on the head-neck segment musculo-tendinous stiffness.
METHODS: Ten men (aged 21.2 +/- 1.9 years) performed four quick-release trials of
flexion at 30 and 50% MVC before and after the induction of muscular fatigue on
cervical flexors. Electromyographic activity was recorded on the
sternocleidomastoids (SCM) and spinal erectors (SE), bilaterally. Musculo
tendinous stiffness was calculated through the quick-release method adapted to
the head-neck segment. RESULTS: We noticed a significant linear increase of the
head-neck segment musculo-tendinous stiffness with the increase of exertion level
both before (P < 0.0001) and after the fatigue procedure (P < 0.0001). However,
this linear relationship was not different before and after the fatigue
procedure. EMG analysis revealed a significant increase of the root mean square
for the right SCM (P = 0.0002), the left SCM (P < 0.0001), the right SE (P <
0.0001), and the left SE (P < 0.0001) and a significant decrease of the median
power frequency only for the right (P = 0.0006) and the left (P = 0.0003) SCM
with muscular fatigue. DISCUSSION: We did not find significant changes in the
head-neck segment musculo-tendinous stiffness with fatigue of cervical muscles.
We found a significant increase in EMG activity in the SCM and the SE after the
induction of fatigue of the SCM. Our findings suggest that with fatigue of
cervical flexors, neck muscle activity is modulated in order to maintain the
musculo-tendinous stiffness at a steady state.
PMID- 26418002
TI - Religious Affiliation Modulates Weekly Cycles of Cropland Burning in Sub-Saharan
Africa.
AB - Vegetation burning is a common land management practice in Africa, where fire is
used for hunting, livestock husbandry, pest control, food gathering, cropland
fertilization, and wildfire prevention. Given such strong anthropogenic control
of fire, we tested the hypotheses that fire activity displays weekly cycles, and
that the week day with the fewest fires depends on regionally predominant
religious affiliation. We also analyzed the effect of land use (anthrome) on
weekly fire cycle significance. Fire density (fire counts.km-2) observed per week
day in each region was modeled using a negative binomial regression model, with
fire counts as response variable, region area as offset and a structured random
effect to account for spatial dependence. Anthrome (settled, cropland, natural,
rangeland), religion (Christian, Muslim, mixed) week day, and their 2-way and 3
way interactions were used as independent variables. Models were also built
separately for each anthrome, relating regional fire density with week day and
religious affiliation. Analysis revealed a significant interaction between
religion and week day, i.e. regions with different religious affiliation
(Christian, Muslim) display distinct weekly cycles of burning. However, the
religion vs. week day interaction only is significant for croplands, i.e. fire
activity in African croplands is significantly lower on Sunday in Christian
regions and on Friday in Muslim regions. Magnitude of fire activity does not
differ significantly among week days in rangelands and in natural areas, where
fire use is under less strict control than in croplands. These findings can
contribute towards improved specification of ignition patterns in regional/global
vegetation fire models, and may lead to more accurate meteorological and chemical
weather forecasting.
PMID- 26418001
TI - Transcriptomic Analysis of the Anterior Silk Gland in the Domestic Silkworm
(Bombyx mori) - Insight into the Mechanism of Silk Formation and Spinning.
AB - Silk proteins are synthesized in the middle and posterior silk glands of
silkworms, then transit into the anterior of the silk gland, where the silk
fibers are produced, stored and processed. The mechanism of formation and
spinning of the silk fibers has not been fully elucidated, and transcriptome
analyses specific to the anterior silk gland have not been reported. In the
present study, we explored gene expression profiles in five regions of silk gland
samples using the RNA-Seq method. As a result, there were 959,979,570 raw reads
obtained, of which 583,068,172 reads were mapped to the silkworm genome. A total
of 7419 genes were found to be expressed in terms of reads per kilobase of exon
model per million mapped reads >= 5 in at least one sample. The gene numbers and
expression levels of the expressed genes differed between these regions. The
differentially expressed genes were analyzed, and 282 genes were detected as up
regulated in the anterior silk gland, compared with the other parts. Functions of
these genes were addressed using the gene ontology and Kyoto Encyclopedia of
Genes and Genomes databases, and seven key pathways were enriched. It suggested
that the ion transportation, energy metabolism, protease inhibitors and cuticle
proteins played essential roles in the process of silk formation and spinning in
the anterior silk gland. In addition, 210 genes were found differently expressed
between males and females, which should help to elucidate the mechanism of the
quality difference in silk fibers from male and female silkworms.
PMID- 26417993
TI - The Application of DNA Barcodes for the Identification of Marine Crustaceans from
the North Sea and Adjacent Regions.
AB - During the last years DNA barcoding has become a popular method of choice for
molecular specimen identification. Here we present a comprehensive DNA barcode
library of various crustacean taxa found in the North Sea, one of the most
extensively studied marine regions of the world. Our data set includes 1,332
barcodes covering 205 species, including taxa of the Amphipoda, Copepoda,
Decapoda, Isopoda, Thecostraca, and others. This dataset represents the most
extensive DNA barcode library of the Crustacea in terms of species number to
date. By using the Barcode of Life Data Systems (BOLD), unique BINs were
identified for 198 (96.6%) of the analyzed species. Six species were
characterized by two BINs (2.9%), and three BINs were found for the amphipod
species Gammarus salinus Spooner, 1947 (0.4%). Intraspecific distances with
values higher than 2.2% were revealed for 13 species (6.3%). Exceptionally high
distances of up to 14.87% between two distinct but monophyletic clusters were
found for the parasitic copepod Caligus elongatus Nordmann, 1832, supporting the
results of previous studies that indicated the existence of an overlooked sea
louse species. In contrast to these high distances, haplotype-sharing was
observed for two decapod spider crab species, Macropodia parva Van Noort & Adema,
1985 and Macropodia rostrata (Linnaeus, 1761), underlining the need for a
taxonomic revision of both species. Summarizing the results, our study confirms
the application of DNA barcodes as highly effective identification system for the
analyzed marine crustaceans of the North Sea and represents an important
milestone for modern biodiversity assessment studies using barcode sequences.
PMID- 26418003
TI - Heat Shock Protein 60 in Eggs Specifically Induces Tregs and Reduces Liver
Immunopathology in Mice with Schistosomiasis Japonica.
AB - BACKGROUND: Parasitic helminths need to suppress the host immune system to
establish chronic infections. Paradoxically, immunosuppression induced by the
worm also benefits the host by limiting excessive inflammation and tissue damage,
which remains the major cause leading to serious morbidity and mortality.
Regulatory T cells (Tregs) are key immune regulators of this mutualism. The
successive rise in Tregs during schistosome infection plays a critical role in
immunoregulation. We and others previously showed that Schistosoma japonicum (S.
japonicum) egg antigens (SEA) induce Tregs both in vitro and in vivo. In
addition, we identified that SjHSP60 derived from SEA significantly induces Tregs
in vivo and in vitro. However, the contribution of SjHSP60 in SEA to Treg
induction and the related mechanisms of the Treg induction have not yet been
identified. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we showed that S.
japonicum stress protein HSP60 (SjHSP60) was constitutively and extensively
expressed in eggs of S. japonicum. SjHSP60 specially induced Tregs in vivo and in
vitro without inducing other CD4+ T sub-populations including Th1, Th2 and Th17
cells. Furthermore, we showed that the SjHSP60-depleted SEA almost lost the
ability in vitro and displayed a significant impaired ability to induce Tregs in
vivo. Finally, our study illustrated that the mechanisms of SjHSP60-mediated
induction of Tregs are through both conversion of CD4+CD25- T cells into
CD4+CD25+Foxp3+ Tregs and expansion of preexisting CD4+CD25+Foxp3+ Tregs in a
TLR4-dependent manner. CONCLUSIONS/SIGNIFICANCE: Collectively, our findings
identify SjHSP60 as a major parasitic contributor of Treg induction in S.
japonicum egg antigens, which not only contributes to the better understanding of
the mechanism of immunoregulation during helminth infection, but also suggests
its potential as a therapeutic target for control of immunopathology, allergic
and autoimmune diseases.
PMID- 26418004
TI - Urbanicity and Paediatric Bacteraemia in Ghana-A Case-Control Study within a
Rural-Urban Transition Zone.
AB - BACKGROUND: Systemic bacterial infections are a major cause of paediatric febrile
illness in sub-Saharan Africa. Aim of this study was to assess the effects of
social and geographical determinants on the risk of bacteraemia in a rural-urban
transition zone in Ghana. METHODS: Children below 15 years of age with fever were
recruited at an outpatient department in the suburban belt of Kumasi, Ghana's
second largest city. Blood was taken for bacterial culture and malaria
diagnostics. The socio-economic status of participants was calculated using
Principle Component Analysis. A scale, based on key urban characteristics, was
established to quantify urbanicity for all communities in the hospital catchment
area. A case-control analysis was conducted, where children with and without
bacteraemia were cases and controls, respectively. RESULTS: Bacteraemia was
detected in 72 (3.1%) of 2,306 hospital visits. Non-typhoidal Salmonella (NTS; n
= 24; 33.3%) and Salmonella typhi (n = 18; 25.0%) were the most common isolates.
Logistic regression analysis showed that bacteraemia was negatively associated
with urbanicity (odds ratio [OR] = 0.8; 95% confidence interval [CI]: 0.7-1.0)
and socio-economic status (OR = 0.8; 95% CI: 0.6-0.9). Both associations were
stronger if only NTS infections were used as cases (OR = 0.5; 95% CI: 0.3-0.8 and
OR = 0.6; 95% CI: 0.4-1.0, respectively). CONCLUSIONS: The results of this study
highlight the importance of individual as well as community factors as
independent risk factors for invasive bacterial infection (IBI) and especially
NTS. Epidemiological data support physicians, public health experts and policy
makers to identify disease prevention and treatment needs in order to secure
public health in the transitional societies of developing countries.
PMID- 26418005
TI - Osteocalcin Is Not Associated with the Risk of Type 2 Diabetes: Findings from the
EPIC-NL Study.
AB - OBJECTIVE: To investigate whether total osteocalcin (tOC), uncarboxylated
osteocalcin (ucOC) and percentage of uncarboxylated osteocalcin (%ucOC) are
associated with the risk of type 2 diabetes. METHODS: This nested case control
study included 1,635 participants, 833 incident diabetes cases and 802 non
diabetic control participants, aged 21-70 years from the EPIC-NL cohort. Baseline
concentrations of tOC, ucOC and %ucOC were assessed. During 10 years of follow
up, diabetes cases were self-reported and verified against information from
general practitioners or pharmacists. The association between the different forms
of osteocalcin and diabetes risk was assessed with logistic regression adjusted
for diabetes risk factors (waist circumference, age, sex, cohort, smoking status,
family history of diabetes, hypertension, alcohol intake, physical activity and
education) and dietary factors (total energy intake and energy adjusted intake of
fat, fiber, protein and calcium). RESULTS: TOC concentration was not associated
with diabetes risk, with an odds ratio (OR) of 0.97 (0.91-1.03) for each ng/ml
increment after adjustment for diabetes risk factors and dietary factors. No
association between ucOC and %ucOC and the risk of diabetes was observed either.
In sex stratified analyses (P interaction = 0.07), higher %ucOC tended to be
associated with an increased risk of type 2 diabetes in a multivariable model in
women (OR 1.05 for each increment of 5% ucOC (1.00-1.11), Ptrend = 0.08), but not
in men (OR 0.96 for each increment of 5% ucOC (0.88-1.04)). When waist
circumference was replaced by body mass index, none of the osteocalcin forms were
associated with the risk of type 2 diabetes in the final model among both women
and men. CONCLUSIONS: Available evidence suggests that tOC, ucOC and %ucOC are
each not associated with the risk of type 2 diabetes. However, more large-scale
cohort studies are needed to clarify the presence of any association between the
different forms of osteocalcin and the risk of type 2 diabetes.
PMID- 26418006
TI - Cytidine Deaminase as a Molecular Predictor of Gemcitabine Response in Patients
with Biliary Tract Cancer.
AB - OBJECTIVE: Gemcitabine-based chemotherapy is regarded as the standard treatment
for biliary tract cancer (BTC). Potential biomarkers for gemcitabine response
include the activities of cytidine deaminase (CDA), human equilibrative
nucleoside transporter 1 (hENT1), deoxycytidine kinase (DCK), and ribonucleotide
reductase M1 (RRM1). Here, we investigated whether single nucleotide
polymorphisms (SNPs) in their encoding genes were associated with the efficacy of
gemcitabine chemotherapy in treating BTC. METHODS: We retrospectively evaluated
11 SNPs in the CDA, hENT1, DCK, human concentrative nucleoside transporter 3
(hCNT3), and RRM1 genes in 80 patients with unresectable, metastatic, or
recurrent BTC who were treated with gemcitabine plus cisplatin. RESULTS: After
the results were adjusted for clinical predictors, the variant allele of
rs1048977 in the CDA gene was associated with tumor response in a dominant model
(OR, 0.23; 95% CI, 0.06-0.93; p = 0.039). No significant association was detected
between the 11 SNPs and grade 3/4 toxicity. CONCLUSIONS: Our findings suggest
that the polymorphism of CDA may be a potential predictive marker for the
efficacy of gemcitabine-based chemotherapy in patients with BTC.
PMID- 26418007
TI - Dual Energy CT Angiography of Peripheral Arterial Disease: Feasibility of Using
Lower Contrast Medium Volume.
AB - OBJECTIVE: One of the main drawbacks associated with Dual Energy Computed
Tomography Angiography (DECTA) is the risk of developing contrast medium-induced
nephropathy (CIN). The aim of the present study was firstly, to design an optimal
CT imaging protocol by determining the feasibility of using a reduced contrast
medium volume in peripheral arterial DECTA, and secondly, to compare the results
with those obtained from using routine contrast medium volume. METHODS: Thirty
four patients underwent DECTA for the diagnosis of peripheral arterial disease.
They were randomly divided into two groups: Group 1 (routine contrast volume
group) with n = 17, injection rate 4-5 ml/s, and 1.5 ml/kg of contrast medium,
and Group 2 ((low contrast volume group), with n = 17, injection rate 4-5ml/s,
and contrast medium volume 0.75 ml/kg. A fast kilovoltage-switching 64-slice CT
scanner in the dual-energy mode was employed for the study. A total of 6 datasets
of monochromatic images at 50, 55, 60, 65, 70 and 75 keV levels were
reconstructed with adaptive statistical iterative reconstruction (ASIR) at 50%. A
4-point scale was the tool for qualitative analysis of results. The two groups
were compared and assessed quantitatively for image quality on the basis of
signal-to-noise ratio (SNR) and contrast-to-noise-ratio (CNR). Radiation and
contrast medium doses were also compared. RESULTS: The overall mean CT
attenuation and mean noise for all lower extremity body parts was significantly
lower for the low volume contrast group (p<0.001), and varied significantly
between groups (p = 0.001), body parts (p<0.001) and keVs (p<0.001). The
interaction between group body parts was significant with CT attenuation and CNR
(p = 0.002 and 0.003 respectively), and marginally significant with SNR (p =
0.047), with minimal changes noticed between the two groups. Group 2 (low
contrast volume group) displayed the lowest image noise between 65 and 70 keV,
recorded the highest SNR and CNR at 65 keV, and produced significantly lower
results with respect to contrast medium volume and duration of contrast injection
(p<0.001). The effect of radiation dose was not statistically significant between
the two groups. CONCLUSIONS: DECTA images created at 65 keV and 50% ASIR with low
contrast medium volume protocol, yielded results that were comparable to routine
contrast medium volume, with acceptable diagnostic images produced during the
evaluation of peripheral arteries.
PMID- 26418008
TI - Structure and Sialyllactose Binding of the Carboxy-Terminal Head Domain of the
Fibre from a Siadenovirus, Turkey Adenovirus 3.
AB - The virulent form of turkey adenovirus 3 (TAdV-3), also known as turkey
hemorrhagic enteritis virus (THEV), is an economically important poultry
pathogen, while the avirulent form is used as a vaccine. TAdV-3 belongs to the
genus Siadenovirus. The carboxy-terminal region of its fibre does not have
significant sequence similarity to any other adenovirus fibre heads of known
structure. Two amino acid sequence differences between virulent and avirulent
TAdV-3 map on the fibre head: where virulent TAdV-3 contains Ile354 and Thr376,
avirulent TAdV-3 contains Met354 and Met376. We determined the crystal structures
of the trimeric virulent and avirulent TAdV-3 fibre head domains at 2.2 A
resolution. Each monomer contains a beta-sandwich, which, surprisingly, resembles
reovirus fibre head more than other adenovirus fibres, although the ABCJ-GHID
topology is conserved in all. A beta-hairpin insertion in the C-strand of each
trimer subunit embraces its neighbouring monomer. The avirulent and virulent TAdV
3 fibre heads are identical apart from the exact orientation of the beta-hairpin
insertion. In vitro, sialyllactose was identified as a ligand by glycan
microarray analysis, nuclear magnetic resonance spectroscopy, and
crystallography. Its dissociation constant was measured to be in the mM range by
isothermal titration calorimetry. The ligand binds to the side of the fibre head,
involving amino acids Glu392, Thr419, Val420, Lys421, Asn422, and Gly423 binding
to the sialic acid group. It binds slightly more strongly to the avirulent form.
We propose that, in vivo, the TAdV-3 fibre may bind a sialic acid-containing cell
surface component.
PMID- 26418009
TI - Involvement of Prolyl Hydroxylase Domain Protein in the Rosiglitazone-Induced
Suppression of Osteoblast Differentiation.
AB - Rosiglitazone is a well-known anti-diabetic drug that increases insulin
sensitivity via peroxisome proliferator-activated receptor gamma (PPARgamma)
activation, but unfortunately it causes bone loss in animals and humans. A
previous study showed that prolyl hydroxylase domain protein (PHD) plays a role
in rosiglitazone-induced adipocyte differentiation. Based on the inverse
relationship between adipocyte and osteoblast differentiation, we investigated
whether PHD is involved in the effects of rosiglitazone on osteoblast
differentiation. Rosiglitazone inhibited osteoblast differentiation in a
concentration-dependent manner, and in parallel induced three PHD isoforms (PHD1,
2, and 3). PHD inhibitors and knockdown of each isoform prevented the inhibitory
effects of rosiglitazone on osteoblast differentiation and increased the
expression of Runx2, a transcription factor essential for osteoblastogenesis. MG
132, a proteasomal inhibitor also prevented the rosiglitazone-induced degradation
of Runx2. Furthermore, both increased PHD isoform expressions and reduced
osteoblast differentiation by rosiglitazone were prevented by PPARgamma
antagonists, indicating these effects were mediated via PPARgamma activation. In
vivo oral administration of rosiglitazone to female ICR mice for 8 weeks reduced
bone mineral densities and plasma alkaline phosphatase (ALP) activity, and
increased PHD expression in femoral primary bone marrow cells and the
ubiquitination of Runx2. Together, this suggests that the rosiglitazone-induced
suppression of osteoblast differentiation is at least partly induced via
PPARgamma-mediated PHD induction and subsequent promotion of the ubiquitination
and degradation of Runx2.
PMID- 26418010
TI - Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast
Derived Mediators.
AB - INTRODUCTION: Abnormal pigmentation following cutaneous injury causes significant
patient distress and represents a barrier to recovery. Wound depth and patient
characteristics influence scar pigmentation. However, we know little about the
pathophysiology leading to hyperpigmentation in healed shallow wounds and
hypopigmentation in deep dermal wound scars. We sought to determine whether
dermal fibroblast signaling influences melanocyte responses. METHODS AND
MATERIALS: Epidermal melanocytes from three Caucasians and three African
Americans were genotyped for single nucleotide polymorphisms (SNPs) across the
entire genome. Melanocyte genetic profiles were determined using principal
component analysis. We assessed melanocyte phenotype and gene expression in
response to dermal fibroblast-conditioned medium and determined potential
mesenchymal mediators by proteome profiling the fibroblast-conditioned medium.
RESULTS: Six melanocyte samples demonstrated significant variability in phenotype
and gene expression at baseline and in response to fibroblast-conditioned medium.
Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast
secreted mediators demonstrated considerable heterogeneity, potentially
explaining the variable melanocyte responses to fibroblast-conditioned medium.
DISCUSSION: Our data suggest that melanocytes respond to dermal fibroblast
derived mediators independent of keratinocytes and raise the possibility that
mesenchymal-epidermal interactions influence skin pigmentation during cutaneous
scarring.
PMID- 26418011
TI - Continuous Metabolic Syndrome Scores for Children Using Salivary Biomarkers.
AB - BACKGROUND: Binary definitions of the metabolic syndrome based on the presence of
a particular number of individual risk factors are limited, particularly in the
pediatric population. To address this limitation, we aimed at constructing
composite and continuous metabolic syndrome scores (cmetS) to represent an
overall measure of metabolic syndrome (MetS) in a large cohort of metabolically
at-risk children, focusing on the use of the usual clinical parameters (waist
circumference (WC) and systolic blood pressure (SBP), supplemented with two
salivary surrogate variables (glucose and high density lipoprotein cholesterol
(HDLC). Two different approaches used to create the scores were evaluated in
comparison. METHODS: Data from 8,112 Kuwaiti children (10.00 +/- 0.67 years) were
used to construct two cmetS for each subject. The first cmetS (cmetS-Z) was
created by summing standardized residuals of each variable regressed on age and
gender; and the second cmetS (cmetS-PCA) was defined as the first principal
component from gender-specific principal component analysis based on the four
variables. RESULTS: There was a graded relationship between both scores and the
number of adverse risk factors. The areas under the curve using cmetS-Z and cmetS
PCA as predictors for severe metabolic syndrome (defined as the presence of >=3
metabolic risk factors) were 0.935 and 0.912, respectively. cmetS-Z was
positively associated with WC, SBP, and glucose, but inversely associated with
HDLC. Except for the lack of association with glucose, cmetS-PCA was similar to
cmetS-Z in boys, but had minimum loading on HDLC in girls. Analysis using
quantile regression showed an inverse association of fitness level with cmetS-PCA
(p = 0.001 for boys; p = 0.002 for girls), and comparison of cmetS-Z and cmetS
PCA suggested that WC and SBP were main contributory components. Significant
alterations in the relationship between cmetS and salivary adipocytokines were
demonstrated in overweight and obese children as compared to underweight and
normal-weight children. CONCLUSION: We have derived continuous summary scores for
MetS from a large-scale pediatric study using two different approaches,
incorporating salivary measures as surrogate for plasma measures. The derived
scores were viable expressions of metabolic risk, and can be utilized to study
the relationships of MetS with various aspects of the metabolic disease process.
PMID- 26418012
TI - Dynamic Data Visualization with Weave and Brain Choropleths.
AB - This article introduces the neuroimaging community to the dynamic visualization
workbench, Weave (https://www.oicweave.org/), and a set of enhancements to allow
the visualization of brain maps. The enhancements comprise a set of brain
choropleths and the ability to display these as stacked slices, accessible with a
slider. For the first time, this allows the neuroimaging community to take
advantage of the advanced tools already available for exploring geographic data.
Our brain choropleths are modeled after widely used geographic maps but this
mashup of brain choropleths with extant visualization software fills an important
neuroinformatic niche. To date, most neuroinformatic tools have provided online
databases and atlases of the brain, but not good ways to display the related data
(e.g., behavioral, genetic, medical, etc). The extension of the choropleth to
brain maps allows us to leverage general-purpose visualization tools for
concurrent exploration of brain images and related data. Related data can be
represented as a variety of tables, charts and graphs that are dynamically linked
to each other and to the brain choropleths. We demonstrate that the simplified
region-based analyses that underlay choropleths can provide insights into
neuroimaging data comparable to those achieved by using more conventional
methods. In addition, the interactive interface facilitates additional insights
by allowing the user to filter, compare, and drill down into the visual
representations of the data. This enhanced data visualization capability is
useful during the initial phases of data analysis and the resulting
visualizations provide a compelling way to publish data as an online supplement
to journal articles.
PMID- 26418013
TI - Correction: Thrombospondin-1 Production Is Enhanced by Porphyromonas gingivalis
Lipopolysaccharide in THP-1 Cells.
PMID- 26418014
TI - Genome Wide Identification of LIM Genes in Cicer arietinum and Response of Ca
2LIMs in Development, Hormone and Pathogenic Stress.
AB - The eukaryotic lineage-specific LIM protein (LIN11, ISL1, and MEC3) family play
pivotal role in modulation of actin dynamics and transcriptional regulation. The
systematic investigation of this family has not been carried in detail and rare
in legumes. Current study involves the mining of Cicer arietinum genome for the
genes coding for LIM domain proteins and displayed significant homology with LIM
genes of other species. The analysis led to the identification of 15 members,
which were positioned on chickpea chromosomes. The phylogenetic and motif
analysis suggested their categorization into two sub-families i.e., Ca-2LIMs and
Ca-DA1/DAR, which comprised of nine and six candidates, respectively. Further sub
categories of Ca-2LIMs were recognised as alphaLIM, betaLIM, deltaLIM and
gammaLIM. The LIM genes within their sub-families displayed conserved genomic and
motif organization. The expression pattern of Ca-2LIMs across developmental and
reproductive tissues demonstrated strong correlation with established consensus.
The Ca-2LIM belongs to PLIM and GLIM (XLIM) was found highly expressed in floral
tissue. Others showed ubiquitous expression pattern with their dominance in stem.
Under hormonal and pathogenic conditions these LIMs were found to up-regulate
during salicylic acid, abscisic acid and Ascochyta rabiei treatment or infection;
and down-regulated in response to jasmonic acid treatment. The findings of this
work, particularly in terms of modulation of LIM genes under biotic stress will
open up the way to further explore and establish the role of chickpea LIMs in
plant defense response.
PMID- 26418015
TI - Cardiorespiratory Adaptations during Concurrent Aerobic and Strength Training in
Men and Women.
AB - This study investigated the effects of endurance followed by strength training
(ES, men n = 16; women n = 15), the reverse exercise order (SE, men n = 18, women
n = 13) and concurrent endurance and strength training performed on alternating
days (AD, men n = 21, women n = 18) on cardiorespiratory parameters. Peak oxygen
consumption ([Formula: see text]O2peak) and oxygen consumption at sub-maximal
power outputs ([Formula: see text]O2submax) of 50 to 175 Watts in men and 50 to
125 Watts in women were assessed during an incremental cycling test both before
and after 24 weeks of training. Increases in [Formula: see text]O2peak in both
men and women were statistically larger in AD (18+/-9% and 25+/-11%) compared to
ES (7+/-9% and 12+/-12%, p = 0.002 and 0.009, respectively) and SE (7+/-9% and
10+/-8%, p = 0.005 and 0.008, respectively). No statistical group interaction was
observed for [Formula: see text]O2submax in men, but in women [Formula: see
text]O2submax was statistically lower at week 24 in ES compared to AD at 75 W (
2+/-6% vs. +3+/-6%, p = 0.027) and 125 W (-4+/-5% vs. +2+/-5%, p = 0.010). These
findings indicate that endurance and strength training performed on alternating
days may optimize the adaptations in [Formula: see text]O2peak in both sexes,
while performing ES training in women may optimize cardiorespiratory fitness at
sub-maximal power outputs.
PMID- 26418017
TI - Lateral Transorbital Endoscopic Access to the Hippocampus, Amygdala, and
Entorhinal Cortex: Initial Clinical Experience.
AB - BACKGROUND/AIMS: Transorbital approaches traditionally have focused on skull base
and cavernous sinus lesions medial to the globe. Lateral orbital approaches to
the temporal lobe have not been widely explored despite several theoretical
advantages compared to open craniotomy. Recently, we demonstrated the feasibility
of the lateral transorbital technique in cadaveric specimens with endoscopic
visualization. We describe our initial clinical experience with the endoscope
assisted lateral transorbital approach to lesions in the temporal lobe. METHODS:
Two patients with mesial temporal lobe pathology presenting with seizures
underwent surgery. The use of a transpalpebral or Stallard-Wright eyebrow
incision enabled access to the intraorbital compartment, and a lateral orbital
wall 'keyhole' opening permitted visualization of the anterior temporal pole.
RESULTS: This approach afforded adequate access to the surgical target and
surrounding structures and was well tolerated by the patients. To the best of our
knowledge, this report constitutes the first case series describing the endoscope
assisted lateral transorbital approach to the temporal lobe. We discuss the
limits of exposure, the nuances of opening and closing, and comparisons to open
craniotomy. CONCLUSION: Further prospective investigation of this approach is
warranted for comparison to traditional approaches to the mesial temporal lobe.
PMID- 26418018
TI - Lysophosphatidic Acid Mediates Activating Transcription Factor 3 Expression Which
Is a Target for Post-Transcriptional Silencing by miR-30c-2-3p.
AB - Although microRNAs (miRNAs) are small, non-protein-coding entities, they have
important roles in post-transcriptional regulation of most of the human genome.
These small entities generate fine-tuning adjustments in the expression of mRNA,
which can mildly or massively affect the abundance of proteins. Previously, we
found that the expression of miR-30c-2-3p is induced by lysophosphatidic acid and
has an important role in the regulation of cell proliferation in ovarian cancer
cells. The goal here is to confirm that ATF3 mRNA is a target of miR-30c-2-3p
silencing, thereby further establishing the functional role of miR-30c-2-3p.
Using a combination of bioinformatics, qRT-PCR, immunoblotting and luciferase
assays, we uncovered a regulatory pathway between miR-30c-2-3p and the expression
of the transcription factor, ATF3. Lysophosphatidic acids triggers the expression
of both miR-30c-2-3p and ATF3, which peak at 1 h and are absent 8 h post
stimulation in SKOV-3 and OVCAR-3 serous ovarian cancer cells. The 3'
untranslated region (3'-UTR) of ATF3 was a predicted, putative target for miR-30c
2-3p, which we confirmed as a bona-fide interaction using a luciferase reporter
assay. Specific mutations introduced into the predicted site of interaction
between miR-30c-2-3p and the 3'-UTR of ATF3 alleviated the suppression of the
luciferase signal. Furthermore, the presence of anti-miR-30c-2-3p enhanced ATF3
mRNA and protein after lysophosphatidic acid stimulation. Thus, the data suggest
that after the expression of ATF3 and miR-30c-2-3p are elicited by
lysophosphatidic acid, subsequently miR-30c-2-3p negatively regulates the
expression of ATF3 through post-transcriptional silencing, which prevents further
ATF3-related outcomes as a consequence of lysophosphatidic acid signaling.
PMID- 26418016
TI - A Review of the Statistical and Quantitative Methods Used to Study Alcohol
Attributable Crime.
AB - Modelling the relationship between alcohol consumption and crime generates new
knowledge for crime prevention strategies. Advances in data, particularly data
with spatial and temporal attributes, have led to a growing suite of applied
methods for modelling. In support of alcohol and crime researchers we synthesized
and critiqued existing methods of spatially and quantitatively modelling the
effects of alcohol exposure on crime to aid method selection, and identify new
opportunities for analysis strategies. We searched the alcohol-crime literature
from 1950 to January 2014. Analyses that statistically evaluated or mapped the
association between alcohol and crime were included. For modelling purposes,
crime data were most often derived from generalized police reports, aggregated to
large spatial units such as census tracts or postal codes, and standardized by
residential population data. Sixty-eight of the 90 selected studies included
geospatial data of which 48 used cross-sectional datasets. Regression was the
prominent modelling choice (n = 78) though dependent on data many variations
existed. There are opportunities to improve information for alcohol-attributable
crime prevention by using alternative population data to standardize crime rates,
sourcing crime information from non-traditional platforms (social media),
increasing the number of panel studies, and conducting analysis at the local
level (neighbourhood, block, or point). Due to the spatio-temporal advances in
crime data, we expect a continued uptake of flexible Bayesian hierarchical
modelling, a greater inclusion of spatial-temporal point pattern analysis, and
shift toward prospective (forecast) modelling over small areas (e.g., blocks).
PMID- 26418019
TI - Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in
Treated Hypertensive Patients: LIFE Study.
AB - In the Losartan Intervention for End Point Reduction in Hypertension (LIFE)
study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment
reduced left ventricular hypertrophy and cardiovascular end points, including
cardiovascular death and stroke. However, there was no difference in myocardial
infarction (MI), possibly related to greater reduction in myocardial oxygen
demand by atenolol-based treatment. Myocardial oxygen demand was assessed
indirectly by the left ventricular mass*wall stress*heart rate (triple product)
in 905 LIFE participants. The triple product was included as time-varying
covariate in Cox models assessing predictors of the LIFE primary composite end
point (cardiovascular death, MI, or stroke), its individual components, and all
cause mortality. At baseline, the triple product in both treatment groups was,
compared with normal adults, elevated in 70% of patients. During randomized
treatment, the triple product was reduced more by atenolol, with prevalences of
elevated triple product of 39% versus 51% on losartan (both P<=0.001). In Cox
regression analyses adjusting for age, smoking, diabetes mellitus, and prior
stroke, MI, and heart failure, 1 SD lower triple product was associated with 23%
(95% confidence interval 13%-32%) fewer composite end points, 31% (18%-41%) less
cardiovascular mortality, 30% (15%-41%) lower MI, and 22% (11%-33%) lower all
cause mortality (all P<=0.001), without association with stroke (P=0.34).
Although losartan-based therapy reduced ventricular mass more, greater heart rate
reduction with atenolol resulted in larger reduction of the triple product. Lower
triple product during antihypertensive treatment was strongly, independently
associated with lower rates of the LIFE primary composite end point,
cardiovascular death, and MI, but not stroke.
PMID- 26418020
TI - 17beta-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes
With Pulmonary Arterial Hypertension.
AB - Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes
women more often than men. Paradoxically, female PAH patients have better
prognosis and survival rates than males. The female sex hormone 17beta-estradiol
has been linked to the better outcome of PAH in females; however, the mechanisms
by which 17beta-estradiol alters PAH progression and outcomes remain unclear.
Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a
powerful predictor of mortality and morbidity, we hypothesized that 17beta
estradiol attenuates PAH-induced changes in mechanical properties in conduit
proximal PAs, which imparts hemodynamic and energetic benefits to right
ventricular function. To test this hypothesis, female mice were ovariectomized
and treated with 17beta-estradiol or placebo. PAH was induced in mice using
SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically
tested ex vivo to study both static and frequency-dependent mechanical behaviors
in the presence or absence of smooth muscle cell activation. Our static
mechanical test showed significant stiffening of large PAs with PAH (P<0.05).
17beta-Estradiol restored PA compliance to control levels. The dynamic mechanical
test demonstrated that 17beta-estradiol protected the arterial wall from the PAH
induced frequency-dependent decline in dynamic stiffness and loss of viscosity
with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics
via right ventricular catheterization, modulation by 17beta-estradiol of
mechanical proximal PAs reduced pulsatile loading, which contributed to improved
ventricular-vascular coupling. This study provides a mechanical mechanism for
delayed disease progression and better outcome in female PAH patients and
underscores the therapeutic potential of 17beta-estradiol in PAH.
PMID- 26418021
TI - Effects of Intrinsic and Extrinsic Cardiac Nerves on Atrial Arrhythmia in
Experimental Pulmonary Artery Hypertension.
AB - Atrial arrhythmia, which includes atrial fibrillation (AF) and atrial flutter
(AFL), is common in patients with pulmonary arterial hypertension (PAH), who
often have increased sympathetic nerve activity. Here, we tested the hypothesis
that autonomic nerves play important roles in vulnerability to AF/AFL in PAH. The
atrial effective refractory period and AF/AFL inducibility at baseline and after
anterior right ganglionated plexi ablation were determined during left stellate
ganglion stimulation or left renal sympathetic nerve stimulation in beagle dogs
with or without PAH. Then, sympathetic nerve, beta-adrenergic receptor densities
and connexin 43 expression in atrial tissues were assessed. The sum of the window
of vulnerability to AF/AFL was increased in the right atrium compared with the
left atrium at baseline in the PAH dogs but not in the controls. The atrial
effective refractory period dispersion was increased in the control dogs, but not
in the PAH dogs, during left stellate ganglion stimulation. The voltage
thresholds for inducing AF/AFL during anterior right ganglionated plexi
stimulation were lower in the PAH dogs than in the controls. The AF/AFL
inducibility was suppressed after ablation of the anterior right ganglionated
plexi in the PAH dogs. The PAH dogs had higher sympathetic nerve and beta1
adrenergic receptor densities, increased levels of nonphosphorylated connexin 43,
and heterogeneous connexin 43 expression in the right atrium when compared with
the control dogs. The anterior right ganglionated plexi play important roles in
the induction of AF/AFL. AF/AFL induction was associated with right atrium
substrate remodeling in dogs with PAH.
PMID- 26418023
TI - Another Piece to the Puzzle: Linking the Cardiac Nervous System to Atrial
Fibrillation in Pulmonary Arterial Hypertension.
PMID- 26418022
TI - Impact of Ivabradine on Central Aortic Blood Pressure and Myocardial Perfusion in
Patients With Stable Coronary Artery Disease.
AB - Treatment of hypertensive patients with beta-blockers reduces heart rate and
decreases central blood pressure less than other antihypertensive drugs, implying
that reducing heart rate without altering brachial blood pressure could increase
central blood pressure, explaining the increased cardiovascular risk reported
with beta-blocker. We describe a randomized, double-blind study to explore
whether heart rate reduction with the If inhibitor ivabradine had an impact on
central blood pressure. We included 12 normotensive patients with stable coronary
artery disease, heart rate >=70 bpm (sinus rhythm), and stable background beta
blocker therapy. Patients received ivabradine 7.5 mg BID or matched placebo for
two 3-week periods with a crossover design and evaluation by aplanation
tonometry. Treatment with ivabradine was associated with a significant reduction
in resting heart rate after 3 weeks versus no change with placebo (-15.8+/-7.7
versus +0.3+/-5.8 bpm; P=0.0010). There was no relevant between-group difference
in change in central aortic systolic blood pressure (-4.0+/-9.6 versus +2.4+/
12.0 mm Hg; P=0.13) or augmentation index (-0.8+/-10.0% versus +0.3+/-7.6%;
P=0.87). Treatment with ivabradine was associated with a modest increase in left
ventricular ejection time (+18.5+/-17.8 versus +2.8+/-19.3 ms; P=0.074) and a
prolongation of diastolic perfusion time (+215.6+/-105.3 versus -3.0+/-55.8 ms
with placebo; P=0.0005). Consequently, ivabradine induced a pronounced increase
in Buckberg index, an index of myocardial viability (+39.3+/-27.6% versus -2.5+/
13.5% with placebo; P=0.0015). In conclusion, heart rate reduction with
ivabradine does not increase central aortic blood pressure and is associated with
a marked prolongation of diastolic perfusion time and an improvement in
myocardial perfusion index. CLINICAL TRIAL REGISTRATION: URL:
https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004779-35.
PMID- 26418024
TI - High B-Type Natriuretic Peptide Hypertensives at Target Blood Pressure: Potential
Role of beta-Blockers to Reduce Their Elevated Risk.
PMID- 26418025
TI - Patent Foramen Ovale Closure in Obstructive Sleep Apnea Improves Blood Pressure
and Cardiovascular Function.
AB - Obstructive sleep apnea (OSA) is a frequent syndrome characterized by
intermittent hypoxemia and increased prevalence of arterial hypertension and
cardiovascular morbidity. In OSA, the presence of patent foramen ovale (PFO) is
associated with increased number of apneas and more severe oxygen desaturation.
We hypothesized that PFO closure improves sleep-disordered breathing and, in
turn, has favorable effects on vascular function and arterial blood pressure. In
40 consecutive patients with newly diagnosed OSA, we searched for PFO. After
initial cardiovascular assessment, the 14 patients with PFO underwent initial
device closure and the 26 without PFO served as control group. Conventional
treatment for OSA was postponed for 3 months in both groups, and polysomnographic
and cardiovascular examinations were repeated at the end of the follow-up period.
PFO closure significantly improved the apnea-hypopnea index (DeltaAHI -7.9+/-10.4
versus +4.7+/-13.1 events/h, P=0.0009, PFO closure versus control), the oxygen
desaturation index (DeltaODI -7.6+/-16.6 versus +7.6+/-17.0 events/h, P=0.01),
and the number of patients with severe OSA decreased significantly after PFO
closure (79% versus 21%, P=0.007). The following cardiovascular parameters
improved significantly in the PFO closure group, although remained unchanged in
controls: brachial artery flow-mediated vasodilation, carotid artery stiffness,
nocturnal systolic and diastolic blood pressure (-7 mm Hg, P=0.009 and -3 mm Hg,
P=0.04, respectively), blood pressure dipping, and left ventricular diastolic
function. In conclusion, PFO closure in OSA patients improves sleep-disordered
breathing and nocturnal oxygenation. This translates into an improvement of
endothelial function and vascular stiffening, a decrease of nighttime blood
pressure, restoration of the dipping pattern, and improvement of left ventricular
diastolic function. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT01780207.
PMID- 26418027
TI - Crystallographic, Electronic, and Magnetic Properties of Rock Salt Superstructure
Sulfide Lu2CrS4 with Jahn-Teller Distortion.
AB - A new chromium(II) sulfide, Lu2CrS4, with a novel structure was prepared by a
solid-state reaction. The powder X-ray diffraction pattern could be indexed as a
tetragonal system, with a = 7.46373(2) A, c = 22.6338(2) A, and space group I42d
(No. 122). Rietveld analysis of the pattern provided the crystal structure
consisting of CrS6 and LuS6 octahedra sharing edges and apexes and revealed a
rock salt superstructure with new cation (vacancy) arrangements. The electrical
resistivity indicates semiconducting behavior. The magnetic susceptibility and
specific heat measurements showed that the Cr ions are in the high-spin d(4)
configuration and that their magnetic moments ordered antiferromagnetically at 55
K. The basic antiferromagnetic structure was determined using powder neutron
diffraction data at 10 K. The band structure calculations demonstrate that the
densities of states of Cr 3d electrons split into two spin-up eg bands because of
Jahn-Teller distortion.
PMID- 26418026
TI - Changes in the Sterol Composition of the Plasma Membrane Affect Membrane
Potential, Salt Tolerance and the Activity of Multidrug Resistance Pumps in
Saccharomyces cerevisiae.
AB - We investigated the impact of the deletions of genes from the final steps in the
biosynthesis of ergosterol (ERG6, ERG2, ERG3, ERG5, ERG4) on the physiological
function of the Saccharomyces cerevisiae plasma membrane by a combination of
biological tests and the diS-C3(3) fluorescence assay. Most of the erg mutants
were more sensitive than the wild type to salt stress or cationic drugs, their
susceptibilities were proportional to the hyperpolarization of their plasma
membranes. The different sterol composition of the plasma membrane played an
important role in the short-term and long-term processes that accompanied the
exposure of erg strains to a hyperosmotic stress (effect on cell size, pH
homeostasis and survival of yeasts), as well as in the resistance of cells to
antifungal drugs. The pleiotropic drug-sensitive phenotypes of erg strains were,
to a large extent, a result of the reduced efficiency of the Pdr5 efflux pump,
which was shown to be more sensitive to the sterol content of the plasma membrane
than Snq2p. In summary, the erg4Delta and erg6Delta mutants exhibited the most
compromised phenotypes. As Erg6p is not involved in the cholesterol biosynthetic
pathway, it may become a target for a new generation of antifungal drugs.
PMID- 26418028
TI - Assessment of Nutritional Status in Children With Cancer and Effectiveness of
Oral Nutritional Supplements.
AB - Malnutrition is a common consequence of cancer in children, but the most
effective methods of nutrition intervention are under debate. We aimed to
evaluate the nutritional status of children diagnosed with cancer, and to
investigate the effect of oral nutritional supplements on anthropometric
measurements, biochemical parameters, and outcome. A randomized clinical study of
45 newly diagnosed cancer patients was performed. Anthropometric and biochemical
data and related factors were assessed at 0, 3, and 6 months after diagnosis. On
initial anthropometric assessment, prevalence of malnutrition by weight or height
was found to be lower as compared with body mass index (BMI), or weight for
height (WFH), or arm anthropometry. Twenty-six of the patients (55%) received
oral nutritional supplement. During the second 3 months after diagnosis, there
was a statistically significant decrease in number of the patients with WFH <90th
percentile and BMI <5th percentile (P = .003 and P = .04, respectively).
Infectious complications occurred more frequently in malnourished patients during
first 3 months, and survival of children who were malnourished at the 6th month
was significantly lower than that of well-nourished children (P = .003). On
laboratory assessment, serum prealbumin levels of the all subjects were below
normal ranges, but no relation was found for serum prealbumin or albumin levels
in patients who were malnourished or not at diagnosis. Nutritional intervention
is necessary to promote normal development and increase functional status as a
child receives intensive treatment. Protein- and energy-dense oral nutritional
supplements are effective for preventing weight loss in malnourished children.
PMID- 26418029
TI - Synthesis, crystal structure and properties of the new superconductors TaRuB and
NbOsB.
AB - Two new ternary compounds TaRuB and NbOsB were synthesized by arc-melting and
annealing at 1500-1850 degrees C. They crystallize in orthorhombic primitive
structures with space group Pbam. Magnetic susceptibility, electrical
resistivity, and specific heat measurements reveal bulk superconductivity for
metallic TaRuB with a T(c) ~ 4 K. Electronic structure calculations by DFT
methods show that 4d and 5d transition-metal states dominate the density of
states (DOS) at the Fermi level E(F) with a pronounced quasi one-dimensional
behaviour along the [0 0 1] direction. Comparison of the calculated DOS at E(F)
with specific heat data reveals a moderate electron-phonon coupling. Possible
small boron vacancies could significantly reduce the DOS at E(F), hence decrease
T(c) for samples annealed at higher temperatures. For NbOsB, the DOS(E(F)) is
strongly reduced due to an increase of covalent bonding interactions between Os
and B. Accordingly, a lower T(c) ~ 1 K is observed.
PMID- 26418030
TI - Interview with Stephen B Baylin.
AB - Stephen B Baylin is a codirector of the Cancer Biology Program at The Sidney
Kimmel Comprehensive Cancer Center at Johns Hopkins and the Virginia and DK
Ludwig Professor of Oncology and Medicine. Baylin attended Duke University, where
he earned his medical degree and completed his internship and first year
residency in internal medicine. He then worked for 2 years at the National Heart
and Lung Institute of the NIH. In 1971, he joined the departments of oncology and
medicine at Johns Hopkins University School of Medicine. His research interests
include cellular biology and genetics of cancer, specifically epigenetics or
genetic modifications other than those in DNA that can affect cell behavior, and
silencing of tumor suppressor genes and tumor progression. His research has
looked at the mechanisms through which variations in tumor cells derive, and cell
differentiation in cancers such as medullary thyroid carcinoma and small-cell
lung carcinoma. He has served on the American Association for Cancer Research
Board of Directors, and is an associate editor of Cancer Research. He has also
presented frequently at AACR conferences and chaired the special conference on
'DNA Methylation, Imprinting and the Epigenetics of Cancer'. He has authored or
coauthored more than 370 publications.
PMID- 26418031
TI - LPA Induces Colon Cancer Cell Proliferation through a Cooperation between the
ROCK and STAT-3 Pathways.
AB - Lysophosphatidic acid (LPA) plays a critical role in the proliferation and
migration of colon cancer cells; however, the downstream signaling events
underlying these processes remain poorly characterized. The aim of this study was
to investigate the signaling pathways triggered by LPA to regulate the mechanisms
involved in the progression of colorectal cancer (CRC). We have used three cell
line models of CRC, and initially analyzed the expression profile of LPA
receptors (LPAR). Then, we treated the cells with LPA and events related to their
tumorigenic potential, such as migration, invasion, anchorage-independent growth,
proliferation as well as apoptosis and cell cycle were evaluated. We used the
Chip array technique to analyze the global gene expression profiling that occurs
after LPA treatment, and we identified cell signaling pathways related to the
cell cycle. The inhibition of these pathways verified the conclusions of the
transcriptomic analysis. We found that the cell lines expressed LPAR1, -2 and -3
in a differential manner and that 10 MUM LPA did not affect cell migration,
invasion and anchorage-independent growth, but it did induce proliferation and
cell cycle progression in HCT-116 cells. Although LPA in this concentration did
not induce transcriptional activity of beta-catenin, it promoted the activation
of Rho and STAT-3. Moreover, ROCK and STAT-3 inhibitors prevented LPA-induced
proliferation, but ROCK inhibition did not prevent STAT-3 activation. Finally, we
observed that LPA regulates the expression of genes related to the cell cycle and
that the combined inhibition of ROCK and STAT-3 prevented cell cycle progression
and increased the LPA-induced expression of cyclins E1, A2 and B1 to a greater
degree than either inhibitor alone. Overall, these results demonstrate that LPA
increases the proliferative potential of colon adenocarcinoma HCT-116 cells
through a mechanism involving cooperation between the Rho-ROCK and STAT3 pathways
involved in cell cycle control.
PMID- 26418033
TI - Myasthenia gravis Lambert-Eaton overlap syndrome.
AB - INTRODUCTION: To assess whether a myasthenia gravis (MG) Lambert-Eaton overlap
syndrome (MLOS) exists. METHODS: Case reports that met the universally accepted
diagnostic criteria for MG and Lambert-Eaton myasthenic syndrome (LEMS) were
sought through a PubMed search. Fifty-five possible cases of MLOS were
identified. RESULTS: Thirty-nine cases met the diagnostic criteria for MG and
LEMS. Analysis of clinical features showed that these patients have common MG and
LEMS symptoms: oculo-bulbar paresis and good response to anti-cholinesterase for
MG and limb weakness and decreased or absent reflexes for LEMS. All had the
classical LEMS pattern in the repetitive nerve stimulation test: low compound
muscle action potential amplitude and incremental response > 60% with brief
exercise or at high rate of stimulation. Eight patients had combined positive
acetylcholine receptor antibody (AChR-ab) or muscle-specific kinase-ab and
voltage-gated calcium channel- ab tests. CONCLUSIONS: A myasthenia gravis Lambert
Eaton overlap syndrome (MLOS) does exist.
PMID- 26418034
TI - Aqueous foams stabilized by temperature-sensitive hairy polymer particles.
AB - Submicrometer-sized polystyrene (PS) particles carrying poly[2
(diethylamino)ethyl methacrylate] (PDEA) hairs (PDEA-PS particles) were
synthesized by free radical dispersion polymerization. The hydrophilicity
hydrophobicity balance of the PDEA could be tuned by varying the temperature at
near neutral pH (a lower critical solution temperature of PDEA at pH 6.86, 41
degrees C) and therefore these sterically-stabilized particles acted as
temperature-sensitive stabilizers for aqueous foams. At 25 degrees C, where the
PDEA hairs were hydrated and PDEA-PS particles were colloidally stable in aqueous
media, foams were formed which coalesced with time and the size of the bubble
increased. At 40 and 45 degrees C, where the PDEA hairs were partially non
hydrated and PDEA-PS particles were close to flocculation or weakly flocculated,
foams were formed and bubble coalescence and size increase speeds were slower
than those observed at 25 degrees C. At and above 50 degrees C, where the PDEA
hairs were non-hydrated and PDEA-PS particles were heavily flocculated in aqueous
media, the more stable cream-like foams whose volume was almost the same for 1
week were formed. Scanning electron microscopy studies indicated that the
particles mainly adsorbed at the air-water interface as monolayers at 25 degrees
C and as multilayers at and above 40 degrees C. The foam stability and structure
could be controlled by changing the temperature.
PMID- 26418032
TI - Synergistic Proinflammatory Responses by IL-17A and Toll-Like Receptor 3 in Human
Airway Epithelial Cells.
AB - Viral respiratory infections activate the innate immune response in the airway
epithelium through Toll-like receptors (TLRs) and induce airway inflammation,
which causes acute exacerbation of asthma. Although increases in IL-17A
expression were observed in the airway of severe asthma patients, the interaction
between IL-17A and TLR activation in airway epithelium remains poorly understood.
In this study, we demonstrated that IL-17A and polyI:C, the ligand of TLR3,
synergistically induced the expression of proinflammatory cytokines and
chemokines (G-CSF, IL-8, CXCL1, CXCL5, IL-1F9), but not type I interferon (IFN
alpha1, -beta) in primary culture of normal human bronchial epithelial cells.
Synergistic induction after co-stimulation with IL-17A and polyI:C was observed
from 2 to 24 hours after stimulation. Treatment with cycloheximide or actinomycin
D had no effect, suggesting that the synergistic induction occurred without de
novo protein synthesis or mRNA stabilization. Inhibition of the TLR3, TLR/TIR
domain-containing adaptor-inducing interferon beta (TRIF), NF-kappaB, and IRF3
pathways decreased the polyI:C- and IL-17A/polyI:C-induced G-CSF and IL-8 mRNA
expression. Comparing the levels of mRNA induction between co-treatment with IL
17A/polyI:C and treatment with polyI:C alone, blocking the of NF-kappaB pathway
significantly attenuated the observed synergism. In western blotting analysis,
activation of both NF-kappaB and IRF3 was observed in treatment with polyI:C and
co-treatment with IL-17A/polyI:C; moreover, co-treatment with IL-17A/polyI:C
augmented IkappaB-alpha phosphorylation as compared to polyI:C treatment alone.
Collectively, these findings indicate that IL-17A and TLR3 activation cooperate
to induce proinflammatory responses in the airway epithelium via TLR3/TRIF
mediated NF-kappaB/IRF3 activation, and that enhanced activation of the NF-kappaB
pathway plays an essential role in synergistic induction after co-treatment with
IL-17A and polyI:C in vitro.
PMID- 26418035
TI - Z-Selective Hydrothiolation of Racemic 1,3-Disubstituted Allenes: An Atom
Economic Rhodium-Catalyzed Dynamic Kinetic Resolution.
AB - A Z-selective rhodium-catalyzed hydrothiolation of 1,3-disubstituted allenes and
subsequent oxidation towards the corresponding allylic sulfones is described.
Using the bidentate 1,4-bis(diphenylphosphino)butane (dppb) ligand, Z/E
selectivities up to >99:1 were obtained. The highly atom-economic
desymmetrization reaction tolerates functionalized aromatic and aliphatic thiols.
Additionally, a variety of symmetric internal allenes, as well as unsymmetrically
disubstituted substrates were well tolerated, thus resulting in high
regioselectivities. Starting from chiral but racemic 1,3-disubstituted allenes a
dynamic kinetic resolution (DKR) could be achieved by applying (S,S)-Me-DuPhos as
the chiral ligand. The desired Z-allylic sulfones were obtained in high yields
and enantioselectivities up to 96 % ee.
PMID- 26418036
TI - Safety challenges of powered two-wheelers.
PMID- 26418037
TI - Assessing proximal risks for acute traumatic events: the case-crossover design.
PMID- 26418040
TI - Low-Dose, Long-Wave UV Light Does Not Affect Gene Expression of Human Mesenchymal
Stem Cells.
AB - Light is a non-invasive tool that is widely used in a range of biomedical
applications. Techniques such as photopolymerization, photodegradation, and
photouncaging can be used to alter the chemical and physical properties of
biomaterials in the presence of live cells. Long-wave UV light (315 nm-400 nm) is
an easily accessible and commonly used energy source for triggering biomaterial
changes. Although exposure to low doses of long-wave UV light is generally
accepted as biocompatible, most studies employing this wavelength only establish
cell viability, ignoring other possible (non-toxic) effects. Since light exposure
of wavelengths longer than 315 nm may potentially induce changes in cell
behavior, we examined changes in gene expression of human mesenchymal stem cells
exposed to light under both 2D and 3D culture conditions, including two different
hydrogel fabrication techniques, decoupling UV exposure and radical generation.
While exposure to long-wave UV light did not induce significant changes in gene
expression regardless of culture conditions, significant changes were observed
due to scaffold fabrication chemistry and between cells plated in 2D versus
encapsulated in 3D scaffolds. In order to facilitate others in searching for more
specific changes between the many conditions, the full data set is available on
Gene Expression Omnibus for querying.
PMID- 26418042
TI - Thermochromism of Cu(I) Tetrakisguanidine Complexes: Reversible Activation of
Metal-to-Ligand Charge-Transfer Bands.
AB - Tetranuclear, intensely blue-coloured Cu(I) complexes were synthesised in which
two Cu2 X3 (-) units (X=Br or I) are bridged by a dicationic GFA (guanidino
functionalised aromatic) ligand. The UV/Vis spectra show a large metal-to-ligand
charge-transfer (MLCT) band around 638 nm. The tetranuclear "low-temperature"
complexes are in a temperature-dependent equilibrium with dinuclear Cu(I) "high
temperature" complexes, which result from the reversible elimination of two CuX
groups. A massive thermochromism effect results from the extinction of the strong
MLCT band upon CuX elimination with increasing temperature. For all complexes,
quantum chemical calculations predict a small and method-dependent energy
difference between the possible electronic structures, namely Cu(I) and
dicationic GFA ligand (closed-shell singlet) versus Cu(II) and neutral GFA ligand
(triplet or broken-symmetry state). The closed-shell singlet state is disfavoured
by hybrid-DFT functionals, which mix in exact Hartree-Fock exchange, and is
favoured by larger basis sets and consideration of a polar medium.
PMID- 26418041
TI - Investigating the Mechanism of Hyperglycemia-Induced Fetal Cardiac Hypertrophy.
AB - Hyperglycemia in diabetic mothers enhances the risk of fetal cardiac hypertrophy
during gestation. However, the mechanism of high-glucose-induced cardiac
hypertrophy is not largely understood. In this study, we first demonstrated that
the incidence rate of cardiac hypertrophy dramatically increased in fetuses of
diabetic mothers using color ultrasound examination. In addition, human fetal
cardiac hypertrophy was successfully mimicked in a streptozotocin (STZ)-induced
diabetes mouse model, in which mouse cardiac hypertrophy was diagnosed using type
M ultrasound and a histological assay. PH3 immunofluorescent staining of mouse
fetal hearts and in vitro-cultured H9c2 cells indicated that cell proliferation
decreased in E18.5, E15.5 and E13.5 mice, and cell apoptosis in H9c2 cells
increased in the presence of high glucose in a dose-dependent manner. Next, we
found that the individual cardiomyocyte size increased in pre-gestational
diabetes mellitus mice and in response to high glucose exposure. Meanwhile, the
expression of beta-MHC and BMP-10 was up-regulated. Nkx2.5 immunofluorescent
staining showed that the expression of Nkx2.5, a crucial cardiac transcription
factor, was suppressed in the ventricular septum, left ventricular wall and right
ventricular wall of E18.5, E15.5 and E13.5 mouse hearts. However, cardiac
hypertrophy did not morphologically occur in E13.5 mouse hearts. In cultured H9c2
cells exposed to high glucose, Nkx2.5 expression decreased, as detected by both
immunostaining and western blotting, and the expression of KCNE1 and Cx43 was
also restricted. Taken together, alterations in cell size rather than cell
proliferation or apoptosis are responsible for hyperglycemia-induced fetal
cardiac hypertrophy. The aberrant expression of Nkx2.5 and its regulatory target
genes in the presence of high glucose could be a principal component of
pathogenesis in the development of fetal cardiac hypertrophy.
PMID- 26418043
TI - Predicting Suicide Intent: The Roles of Experiencing or Committing Violent Acts.
AB - According to the interpersonal theory of suicide (Joiner, 2005), repeated
exposure to painful or provocative experiences is associated with lethal or
nearly lethal suicide attempts. However, suicide research often focuses on
suicide ideation or attempts, rather than intent. Using data from the
Collaborative Psychiatric Epidemiological Surveys, we examined traumatic
experiences, with a focus on repeated exposure to traumas, in individuals who
described their suicide attempts as a strong intent to die versus a cry for help.
Only repeated acts of committing violence were associated with high suicide
intent, suggesting that individuals who engage in violence are at heightened risk
for suicide.
PMID- 26418044
TI - Auditory Training Effects on the Listening Skills of Children With Auditory
Processing Disorder.
AB - OBJECTIVES: Children with auditory processing disorder (APD) typically present
with "listening difficulties,"' including problems understanding speech in noisy
environments. The authors examined, in a group of such children, whether a 12
week computer-based auditory training program with speech material improved the
perception of speech-in-noise test performance, and functional listening skills
as assessed by parental and teacher listening and communication questionnaires.
The authors hypothesized that after the intervention, (1) trained children would
show greater improvements in speech-in-noise perception than untrained controls;
(2) this improvement would correlate with improvements in observer-rated
behaviors; and (3) the improvement would be maintained for at least 3 months
after the end of training. DESIGN: This was a prospective randomized controlled
trial of 39 children with normal nonverbal intelligence, ages 7 to 11 years, all
diagnosed with APD. This diagnosis required a normal pure-tone audiogram and
deficits in at least two clinical auditory processing tests. The APD children
were randomly assigned to (1) a control group that received only the current
standard treatment for children diagnosed with APD, employing various
listening/educational strategies at school (N = 19); or (2) an intervention group
that undertook a 3-month 5-day/week computer-based auditory training program at
home, consisting of a wide variety of speech-based listening tasks with competing
sounds, in addition to the current standard treatment. All 39 children were
assessed for language and cognitive skills at baseline and on three outcome
measures at baseline and immediate postintervention. Outcome measures were
repeated 3 months postintervention in the intervention group only, to assess the
sustainability of treatment effects. The outcome measures were (1) the mean
speech reception threshold obtained from the four subtests of the listening in
specialized noise test that assesses sentence perception in various
configurations of masking speech, and in which the target speakers and test
materials were unrelated to the training materials; (2) the Children's Auditory
Performance Scale that assesses listening skills, completed by the children's
teachers; and (3) the Clinical Evaluation of Language Fundamental-4 pragmatic
profile that assesses pragmatic language use, completed by parents. RESULTS: All
outcome measures significantly improved at immediate postintervention in the
intervention group only, with effect sizes ranging from 0.76 to 1.7. Improvements
in speech-in-noise performance correlated with improved scores in the Children's
Auditory Performance Scale questionnaire in the trained group only. Baseline
language and cognitive assessments did not predict better training outcome.
Improvements in speech-in-noise performance were sustained 3 months
postintervention. CONCLUSIONS: Broad speech-based auditory training led to
improved auditory processing skills as reflected in speech-in-noise test
performance and in better functional listening in real life. The observed
correlation between improved functional listening with improved speech-in-noise
perception in the trained group suggests that improved listening was a direct
generalization of the auditory training.
PMID- 26418045
TI - Everyday Listening Performance of Children Before and After Receiving a Second
Cochlear Implant: Results Using the Parent Version of the Speech, Spatial, and
Qualities of Hearing Scale.
AB - OBJECTIVES: To evaluate change in individual children's performance in general
areas of everyday listening following sequential bilateral implantation, and to
identify the specific types of listening scenarios in which performance change
occurred. The first hypothesis was that parent performance ratings for their
child would be higher in the bilateral versus unilateral implant condition for
each section of the speech, spatial and qualities of hearing scale for parents,
viz.: speech perception, spatial hearing, and qualities of hearing. The second
hypothesis was that the rating for the participant group would be higher in the
bilateral condition for speech perception items involving group conversation or
background noise, spatial hearing items, and qualities of hearing items focused
on sound segregation or listening effort. DESIGN: Children receiving sequential
bilateral implants at the Royal Victorian Eye and Ear Hospital and fulfilling
selection criteria (primarily no significant cognitive or developmental delays,
and oral English language skills of child and parent sufficient for completing
assessments) were invited to participate in a wider project evaluating outcomes.
The assessment protocol for older children included the speech, spatial, and
qualities of hearing scale for parents. All children (n = 20; ages 4 to 15 years)
whose parents completed the scale preoperatively and at 24-months postoperatively
were included in this study. Ratings obtained preoperatively in the unilateral
implant condition (or unilateral implant plus hearing aid for 4 participants)
were compared with those obtained postoperatively in the bilateral implant
condition. RESULTS: Bilateral ratings were significantly higher than unilateral
ratings on the speech section for 12 children (W >= 7.0; p <= 0.03), on the
spatial section for 13 children (W >= 15.0; p <= 0.03), and on the qualities of
hearing section for 9 children (W >= 15.0; p <= 0.047). The difference between
conditions was unrelated to time between implants or age at bilateral
implantation (r <= 0.4; p >= 0.082). The median bilateral ratings for the
participant group were higher for all eight speech perception items, including,
as predicted, those involving group conversation and/or background noise (W >=
37.5; p <= 0.043). Also, as predicted, the median bilateral ratings for the
participant group were higher for all six spatial hearing items (W >= 88.0; p <=
0.014), and for qualities of hearing items related to sound segregation (W >=
94.0; p <= 0.029), but not for those related to listening effort (W <= 92.0; p >=
0.112). CONCLUSIONS: Seventy-five percentage of parents perceived change in their
child's daily listening performance postoperatively, and 25% perceived change
across all three listening areas. For the overall participant group, the parents
perceived a change in performance in the majority of specific listening
scenarios, although change was limited in the qualities of hearing section,
including no change in listening effort. Previous research suggests postoperative
change was likely due to the headshadow effect and improved spatial hearing.
Additional contributions may have been made by binaural summation, redundancy,
and unmasking. For these participants, differences between device conditions may
have been limited by their relatively old age at implantation, delay between
implants, and limited bilateral experience. These results will provide valuable
information to families during preoperative counseling and postoperative
discussions about expected progress and evident benefit.
PMID- 26418046
TI - Search for Allergens from the Pollen Proteome of Sunflower (Helianthus annuus
L.): A Major Sensitizer for Respiratory Allergy Patients.
AB - BACKGROUND: Respiratory allergy triggered by pollen allergens is increasing at an
alarming rate worldwide. Sunflower pollen is thought to be an important source of
inhalant allergens. Present study aims to identify the prevalence of sunflower
pollinosis among the Indian allergic population and characterizes the pollen
allergens using immuno-proteomic tools. METHODOLOGY: Clinico-immunological tests
were performed to understand the prevalence of sensitivity towards sunflower
pollen among the atopic population. Sera from selected sunflower positive
patients were used as probe to detect the IgE-reactive proteins from the one and
two dimensional electrophoretic separated proteome of sunflower pollen. The
antigenic nature of the sugar moiety of the glycoallergens was studied by meta
periodate modification of IgE-immunoblot. Finally, these allergens were
identified by mass-spectrometry. RESULTS: Prevalence of sunflower pollen
sensitization was observed among 21% of the pollen allergic population and
associated with elevated level of specific IgE and histamine in the sera of these
patients. Immunoscreening of sunflower pollen proteome with patient sera detected
seven IgE-reactive proteins with varying molecular weight and pI. Hierarchical
clustering of 2D-immunoblot data highlighted three allergens characterized by a
more frequent immuno-reactivity and increased levels of IgE antibodies in the
sera of susceptible patients. These allergens were considered as the major
allergens of sunflower pollen and were found to have their glycan moiety critical
for inducing IgE response. Homology driven search of MS/MS data of these IgE
reactive proteins identified seven previously unreported allergens from sunflower
pollen. Three major allergenic proteins were identified as two pectate lyases and
a cysteine protease. CONCLUSION: Novelty of the present report is the
identification of a panel of seven sunflower pollen allergens for the first time
at immuno-biochemical and proteomic level, which substantiated the clinical
evidence of sunflower allergy. Further purification and recombinant expression of
these allergens will improve component-resolved diagnosis and therapy of pollen
allergy.
PMID- 26418048
TI - Recombinant hepatitis C viruses that might hamper accurate genotype
classification and choice of treatment with direct-acting agents, southeastern
France.
PMID- 26418047
TI - Breast Cancer Cell Line Aggregate Morphology Does Not Predict Invasive Capacity.
AB - To invade and metastasize to distant loci, breast cancer cells must breach the
layer of basement membrane surrounding the tumor and then invade through the
dense collagen I-rich extracellular environment of breast tissue. Previous
studies have shown that breast cancer cell aggregate morphology in basement
membrane extract correlated with cell invasive capacity in some contexts.
Moreover, cell lines from the same aggregate morphological class exhibited
similarities in gene expression patterns. To further assess the capacity of cell
and aggregate morphology to predict invasive capacity in physiologically relevant
environments, six cell lines with varied cell aggregate morphologies were
assessed in a variety of assays including a 3D multicellular invasion assay that
recapitulates cell-cell and cell-environment contacts as they exist in vivo in
the context of the primary breast tumor. Migratory and invasive capacities as
measured through a 2D gap assay and a 3D spheroid invasion assay reveal that
breast cancer cell aggregate morphology alone is insufficient to predict
migratory speed in 2D or invasive capacity in 3D. Correlations between the 3D
spheroid invasion assay and gene expression profiles suggest this assay as an
inexpensive functional method to predict breast cancer invasive capacity.
PMID- 26418049
TI - Cortical control of facial expression.
AB - The present Review deals with the motor control of facial expressions in humans.
Facial expressions are a central part of human communication. Emotional face
expressions have a crucial role in human nonverbal behavior, allowing a rapid
transfer of information between individuals. Facial expressions can be either
voluntarily or emotionally controlled. Recent studies in nonhuman primates and
humans have revealed that the motor control of facial expressions has a
distributed neural representation. At least five cortical regions on the medial
and lateral aspects of each hemisphere are involved: the primary motor cortex,
the ventral lateral premotor cortex, the supplementary motor area on the medial
wall, and the rostral and caudal cingulate cortex. The results of studies in
humans and nonhuman primates suggest that the innervation of the face is
bilaterally controlled for the upper part and mainly contralaterally controlled
for the lower part. Furthermore, the primary motor cortex, the ventral lateral
premotor cortex, and the supplementary motor area are essential for the voluntary
control of facial expressions. In contrast, the cingulate cortical areas are
important for emotional expression, because they receive input from different
structures of the limbic system.
PMID- 26418050
TI - Conventions and nomenclature for double diffusion encoding NMR and MRI.
AB - Stejskal and Tanner's ingenious pulsed field gradient design from 1965 has made
diffusion NMR and MRI the mainstay of most studies seeking to resolve
microstructural information in porous systems in general and biological systems
in particular. Methods extending beyond Stejskal and Tanner's design, such as
double diffusion encoding (DDE) NMR and MRI, may provide novel quantifiable
metrics that are less easily inferred from conventional diffusion acquisitions.
Despite the growing interest on the topic, the terminology for the pulse
sequences, their parameters, and the metrics that can be derived from them
remains inconsistent and disparate among groups active in DDE. Here, we present a
consensus of those groups on terminology for DDE sequences and associated
concepts. Furthermore, the regimes in which DDE metrics appear to provide
microstructural information that cannot be achieved using more conventional
counterparts (in a model-free fashion) are elucidated. We highlight in particular
DDE's potential for determining microscopic diffusion anisotropy and microscopic
fractional anisotropy, which offer metrics of microscopic features independent of
orientation dispersion and thus provide information complementary to the
standard, macroscopic, fractional anisotropy conventionally obtained by diffusion
MR. Finally, we discuss future vistas and perspectives for DDE.
PMID- 26418051
TI - Isomerization and fragmentation pathways of 1,2-azaborine.
AB - The generation of 1,2-azaborine (4), the BN-analogue of ortho-benzyne, was
recently achieved by elimination of tert-butyldimethylchlorosilane under the
conditions of flash vacuum pyrolysis. The present investigation identifies by
computational means pathways for the thermal isomerization and fragmentation of
1,2-azaborine. The computations were performed using single reference
(hybrid/density functional, second order Moller-Plesset perturbation, and coupled
cluster theories) as well as multiconfiguration methods (complete active space
SCF based second order perturbation theory, multireference configuration
interaction, and multiconfiguration coupled electron pair approximation) with
basis sets up to polarized triple-zeta quality. The 1,2-azaborine is, despite the
distortion of its molecular structure, the most stable C4H4BN isomer
investigated. The formation of BN-endiyne isomers is highly unfavorable as the
identified pathways involve barriers close to 80 kcal mol(-1). The concerted
fragmentation to ethyne and 2-aza-3-bora-butadiyne even has a barrier close to
120 kcal mol(-1). The fragmentation of BN-enediynes has energetic requirements
similar to enediynes.
PMID- 26418052
TI - Correction: Investigating the Goldilocks Hypothesis: The Non-Linear Impact of
Positive Trait Change on Well-Being.
PMID- 26418053
TI - Mesostructured TiO2 Gated Periodic Mesoporous Organosilica-Based Nanotablets for
Multistimuli-responsive Drug Release.
AB - A multistimuli-responsive drug carrier is designed and successfully synthesized
by self-assembly of thiol-modified periodic mesoporous organosilica (PMO)
nanoparticles, coated gold nanoparticles (AuNPs), and mesostructured titanium
dioxide (TiO2). Dye-loaded PMO-Au@TiO2 nanotablets are shown to respond to
environmental changes (pH, temperature, and light) to achieve controlled release.
PMID- 26418055
TI - A Ranking Approach for Probe Selection and Classification of Microarray Data with
Artificial Neural Networks.
AB - Acute leukemia classification into its myeloid and lymphoblastic subtypes is
usually accomplished according to the morphology of the tumor. Nevertheless, the
subtypes may have similar histopathological appearance, making screening
procedures difficult. In addition, approximately one-third of acute myeloid
leukemias are characterized by aberrant cytoplasmic localization of nucleophosmin
(NPMc(+)), where the majority has a normal karyotype. This work is based on two
DNA microarray datasets, available publicly, to differentiate leukemia subtypes.
The datasets were split into training and test sets, and feature selection
methods were applied. Artificial neural network classifiers were developed to
compare the feature selection methods. For the first dataset, 50 genes selected
using the best classifier was able to classify all patients in the test set. For
the second dataset, five genes yielded 97.5% accuracy in the test set.
PMID- 26418056
TI - Human Papillomavirus Genome-Wide Identification of T-Cell Epitopes for Peptide
Vaccine Development Against Cervical Cancer: An Integration of Computational
Analysis and Experimental Assay.
AB - Human papillomavirus (HPV) has long been documented as the primary factor causing
cervical cancer and other complications, and development of immunotherapeutic
vaccines against HPV is thought to be an important approach in preventing women
from HPV infections. It is known that the first step in vaccine development is to
find potent T-cell epitopes in HPV proteins that can be effectively recognized
and presented by the human leukocyte antigen (HLA) system. In the current study,
we proposed a synthetic pipeline that integrates computational analysis and
experimental assay to discover new peptide epitopes from HPV genome with high
affinity to the HLA-A*0201, one of the most frequent HLA allele in Caucasian and
Asian populations. In the procedure, a structure-based three-dimensional
quantitative structure-activity relationship (3D-QSAR) methodology was described
and several 3D-QSAR predictors were established using a set of activity-known HLA
binders. The best predictor was then employed to perform extrapolation over the
HPV genome to screen potential protein fragments with high HLA binding potency.
Consequently, 10 peptides were suggested as promising candidates and their
affinities toward HLA-A*0201 were assayed using a standard T2 cell surface
stabilization test. Four peptides--LLITSNINA from protein E1 (BL50 = 7244 nM),
VLLCVCLLI from protein E5 (BL50 = 9118 nM), VLLLWITAA from protein E5 (BL50 =
3388 nM), and LLMGTLGIV from protein E7 (BL50 = 5500 nM)--were identified as high
affinity binders. Further, the structural basis and binding mode of HLA-A*0201
LLITSNINA complex was examined in detail, revealing a complicated network of
nonbonded interactions across the complex interface that should render high
stability and specificity for the interaction system.
PMID- 26418054
TI - Providing Access to Genomic Variant Knowledge in a Healthcare Setting: A Vision
for the ClinGen Electronic Health Records Workgroup.
AB - The Clinical Genome Resource (ClinGen) is a National Institutes of Health (NIH)
funded collaborative program that brings together a variety of projects designed
to provide high-quality, curated information on clinically relevant genes and
variants. ClinGen's EHR (Electronic Health Record) Workgroup aims to ensure that
ClinGen is accessible to providers and patients through EHR and related systems.
This article describes the current scope of these efforts and progress to date.
The ClinGen public portal can be accessed at www.clinicalgenome.org.
PMID- 26418057
TI - Polyclonal and monoclonal antibodies in renal transplant: an update.
AB - PURPOSE OF REVIEW: There are several monoclonal and polyclonal antibodies used in
renal transplantation today, this article will discuss several agents, their
updates and newer agents. RECENT FINDINGS: Antithymocyte globulin and interleukin
2 (IL-2) receptor blocker continue to be used as induction agents. The risk of
acute rejection was higher in IL-2 receptor blockers mainly in the first year,
but graft survivals were similar in both groups long term. Belatacept is the only
approved intravenous maintenance immunosuppressive therapy which provides the
benefit of glomerular filtration rate preservation, but it was associated with a
higher risk of acute rejection and post-transplant lymphoproliferative disorder.
Bortezomib may help decrease donor-specific antibody levels, but there are
limited data to support its use for desensitization or rejection. Eculizumab may
help in antibody-mediated rejection in some cases but has not shown promising
long-term effects in high-risk individuals. Newer agents have been continuously
tested for improved efficacy and safety. SUMMARY: Transplantation is the standard
of care for end-stage renal disease patients, but we still have a long way to go,
as we need to improve long-term outcomes. The manipulation of the immune system
is a delicate undertaking, with risks of adverse events; therefore, risk versus
benefit needs to be carefully evaluated and treatment needs to be individualized.
PMID- 26418058
TI - Nutrition, vitamin D, and health outcomes in hemodialysis: time for a feeding
frenzy?
AB - PURPOSE OF REVIEW: The role of nutrition and nutritional supplementation in
dialysis recently has been reinvigorated, with small clinical trials exploring
surrogate outcomes and larger epidemiologic studies generating treatment
hypotheses requiring further study. The present review focuses on major aspects
of nutrition and outcomes in hemodialysis patients: protein and calorie intake
and nutritional vitamin D supplementation. RECENT FINDINGS: Building on data from
small studies, two large, quasi-experimental cohort studies showed significant
mortality benefits associated with oral nutritional supplements provided during
dialysis, suggesting potential options for ameliorating the protein-energy
wasting that is common in dialysis patients and associated with poor outcomes.
Multiple cohort studies suggest, both in the general population and in dialysis,
that higher 25(OH) vitamin D levels are associated with improved outcomes;
however, no major mortality trials exist in dialysis, and the smaller, surrogate
studies conducted to date have been disappointing, showing no consistent benefits
in surrogate outcomes including inflammation and anemia, despite appropriate
responses of vitamin D levels to repletion. SUMMARY: Nutritional interventions
are attractive options for improving outcomes in dialysis patients. Nutritional
protein supplements have considerable promise, but require further study,
preferably in a large, generalizable pragmatic trial. Small nutritional vitamin D
supplementation trials in dialysis have had disappointing results. In the absence
of new data, there appears to be no role for routine assessment or repletion of
25(OH) vitamin D deficiency or insufficiency in dialysis.
PMID- 26418059
TI - Acute kidney: improving the pathway of care for patients and across healthcare.
AB - PURPOSE OF REVIEW: Acute kidney injury (AKI) is common, harmful and of global
concern. There is a need to understand the pathway of the management of AKI in
order to identify potential areas where care can be improved, for the individual
and for healthcare systems. RECENT FINDINGS: There has been considerable focus on
risk assessment and earlier detection using changes in serum creatinine. There is
less understanding of optimal management, enhanced and long-term recovery, and
education to support better care. Using Kidney Disease Improving Global Outcomes
based criteria to improve the detection of AKI improves its detection, but
requires supportive training and education to deliver better outcomes.Policy
makers need to understand the personal and economic burden that results from AKI.
There is a need to provide commissioning support, improvement methodologies, and
registry initiatives with research investment to sustain progress in overall
management. SUMMARY: There is clear evidence of harm related to AKI and a need to
improve the reliability of care. The prevalence is high, with the potential to
significantly improve short-term and long-term care by addressing all the
elements in the pathway, at both patient and system level, assessing risk,
detection, treatment, and recovery.
PMID- 26418060
TI - Current status on the evaluation and management of the highly sensitized kidney
transplant recipient.
AB - PURPOSE OF REVIEW: In light of the recent changes to the kidney allocation system
(KAS) and the observed increase in the rate of transplantation of the highly
sensitized kidney transplant candidate, the evaluation and care of this
population is a timely topic. RECENT FINDINGS: In its first year, the new KAS has
already realized one goal of improving the chances of transplanting the most
highly sensitized patients in the waiting list. This has brought to the forefront
the need for recipient readiness in this special population, as well as the need
for histocompatibility labs and kidney transplant programs to align themselves
with each other, and also with the requirements of the United Network for Organ
Sharing, and increase proficiency in testing and data interpretation. This
manuscript is a review of the literature as well as practice patterns as they
relate to the changes in KAS and the observed outcome since the activation of the
new KAS, with the ultimate goal of aiding in the development of a more unified
approach in the care of this specialized population which will allow for
interdisciplinary and cross centre dialogue to optimize long term care and
outcomes. SUMMARY: Here we will review the changes to the KAS as they affect the
highly sensitized kidney transplant recipient, and additional considerations in
the evaluation and management of these patients.
PMID- 26418061
TI - Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non
Invasive Assessment Methods and Liver Biopsy.
AB - OBJECTIVES: To evaluate the diagnostic performance of seven non-invasive tests
(NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV
co-infected patients. METHODS: Transient elastography (TE) and six blood tests
were compared to histopathological fibrosis stage (METAVIR). Participants were
followed over three years with NITs at yearly intervals. RESULTS: Area under the
receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2)
in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test
(0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore
(0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI
(0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid
(0.79). A three year follow-up was completed by 87 participants, all on
antiretroviral therapy and in 20 patients who completed HCV treatment (9 with
sustained virologic response). TE, APRI and Fibrotest did not significantly
change during follow-up. There was weak evidence for an increase of FIB-4 (mean
increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38
participants with F0-F3 at baseline, 10 were progessors (1-stage increase in
fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean
increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results
did not change over 3 years. CONCLUSION: TE was the best NIT for liver fibrosis
staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and
ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good
as more expensive tests. NITs did not change significantly during a follow-up of
three years, suggesting slow liver disease progression in a majority of HIV/HCV
co-infected persons on antiretroviral therapy.
PMID- 26418062
TI - Clinical Characteristics of Preschool Children with Oppositional Defiant Disorder
and Callous-Unemotional Traits.
AB - There is a need to know whether callous-unemotional (CU) traits identify a more
severe group of oppositional defiant children (ODD). The aim of this study is to
ascertain cross-sectionally and longitudinally the specific contribution of CU
levels and the presence of ODD in the psychological state of preschool children
from the general population. A total of 622 children were assessed longitudinally
at ages 3 and 5 with a semi-structured diagnostic interview and questionnaires
filled out by parents and teachers. In multivariate models simultaneously
including ODD diagnosis and CU levels, controlling by socioeconomic status,
ethnicity, sex, severity of conduct disorder symptoms and other comorbidity, high
CU scores were related to higher levels of aggression, withdrawn, externalizing
and global symptomatology, functional impairment and higher probability of
comorbid disorders and use of services. The contribution of CU traits on
children's psychological state was not moderated by the presence/absence of ODD.
Stability for CU traits and number of ODD-symptoms between ages 3 and 5 was
statistically significant but moderate-low (intra-class correlation under .40).
Assessment and identification of CU traits from preschool might help to identify
a subset of children who could have socialization problems, not only among those
with ODD but also among those without a diagnosis of conduct problems.
PMID- 26418063
TI - The Experience of Treating Drooling with Repeated Botulinum Toxin Injections.
AB - Botulinum toxin A (BTX-A) injections to the salivary glands are effective in the
treatment of drooling, and complications are rare. However, there are only a few
previous reports on the long-term use of BTX-A injections. This study
retrospectively analyzes our experience of treating drooling with repeated BTX-A
injections in patients with neurodegenerative diseases. All patients who received
repeated BTX-A injections to the submandibular glands at Tampere University
Hospital in 2004-2013 were included in the analysis. Six patients, aged from 6 to
21 years, were included in the study, and a total of 41 bilateral BTX-A
injections were administered to their submandibular glands. The average number of
injections per patient was 6 (range: 3-11). The average interval between the
injections was 9.8 months (range: 4-18), and 95% (39/41) of the injections were
performed with good response. The complication rate of the BTX-A injections was
2.4% (1/41), since one of the patients had swallowing problems after an
injection. BTX-A injections to the submandibular glands are effective and have a
low morbidity rate, and repeated injections can be recommended as long-term
treatment of drooling.
PMID- 26418064
TI - B-Cell Responses to Human Bocaviruses 1-4: New Insights from a Childhood Follow
Up Study.
AB - Human bocaviruses (HBoVs) 1-4 are recently discovered, antigenically similar
parvoviruses. We examined the hypothesis that the antigenic similarity of these
viruses could give rise to clinically and diagnostically important immunological
interactions. IgG and IgM EIAs as well as qPCR were used to study ~2000 sera
collected from infancy to early adolescence at 3-6-month intervals from 109
children whose symptoms were recorded. We found that HBoV1-4-specific
seroprevalences at age 6 years were 80%, 48%, 10%, and 0%, respectively. HBoV1
infections resulted in significantly weaker IgG responses among children who had
pre-existing HBoV2 IgG, and vice versa. Furthermore, we documented a complete
absence of virus type-specific immune responses in six viremic children who had
pre-existing IgG for another bocavirus, indicating that not all HBoV infections
can be diagnosed serologically. Our results strongly indicate that interactions
between consecutive HBoV infections affect HBoV immunity via a phenomenon called
"original antigenic sin", cross-protection, or both; however, without evident
clinical consequences but with important ramifications for the serodiagnosis of
HBoV infections. Serological data is likely to underestimate human exposure to
these viruses.
PMID- 26418065
TI - Long-Term Cognitive and Behavioral Outcomes following Resolution of Sleep
Disordered Breathing in Preschool Children.
AB - This study aimed to determine the long term effects of resolution of SDB in
preschool children, either following treatment or spontaneous recovery, on
cognition and behavior. Children diagnosed with SDB at 3-5y (N = 35) and non
snoring controls (N = 25), underwent repeat polysomnography (PSG) and cognitive
and behavioral assessment 3 years following a baseline study. At follow-up,
children with SDB were grouped into Resolved and Unresolved. Resolution was
defined as: obstructive apnea hypopnea index (OAHI) <=1 event/h; no snoring
detected on PSG; and no parental report of habitual snoring. 57% (20/35) of
children with SDB received treatment, with SDB resolving in 60% (12/20). 43%
(15/35) were untreated, of whom 40% (6/15) had spontaneous resolution of SDB.
Cognitive reduced between baseline and follow-up, however this was not related to
persistent disease, with no difference in cognitive outcomes between Resolved,
Unresolved or Control groups. Behavioral functioning remained significantly worse
in children originally diagnosed with SDB compared to control children,
regardless of resolution. Change in OAHI did not predict cognitive or behavioral
outcomes, however a reduction in nocturnal arousals, irrespective of full
resolution, was associated with improvement in attention and aggressive behavior.
These results suggest that resolution of SDB in preschool children has little
effect on cognitive or behavioral outcomes over the long term. The association
between sleep fragmentation and behavior appears independent of SDB, however may
be moderated by concomitant SDB. This challenges the assumption that treatment of
SDB will ameliorate associated cognitive and behavioural deficits and supports
the possibility of a SDB phenotype.
PMID- 26418066
TI - An exceptional overall survival using bevacizumab beyond progression in a patient
with non-small cell lung cancer.
AB - Non-small cell lung cancer (NSCLC) is the most common malignancy and the leading
cause of cancer death worldwide. In this report, we describe a patient with NSCLC
who was treated with continuation of Bevacizumab (Bev) beyond progression to
first-line Bev-based chemotherapy. The prolonged treatment with Bev by continuing
the inhibition of VEGF beyond first-progression has a strong rationale.
Nevertheless, few data exist regarding the efficacy and safety of Bev beyond
first line of chemotherapy progression in NSCLC patients. Further studies
including a large number of patients are needed, in order to select patients who
could benefit from this approach.
PMID- 26418068
TI - The Effect of Human Serum Albumin and Hematocrit on the Cake Collapse Temperature
of Lyophilized Red Blood Cells.
AB - Freeze-drying, or lyophilization, has shown great promise in addressing many of
the logistical challenges of storing and preserving red blood cells (RBCs). A
crucial part of any RBC lyophilization protocol is the primary drying
temperature, which affects the sample drying rate and the dried cake's ability to
form a stable glassy solid. Primary drying is most efficient just below the
temperature at which the porous structure of the cake begins to collapse, known
as the cake collapse temperature. In this short report, we utilize freeze-drying
microscopy to examine the effects of human serum albumin (HSA) and hematocrit on
the cake collapse temperature. Increasing the hematocrit from 0% to 20%
significantly raised the cake collapse temperature from - 37.8 degrees C to -34.8
degrees C. Addition of 5% HSA to a 20% hematocrit RBC suspension further
increased the cake collapse temperature to -20.4 degrees C. These data provide a
basis for future study of the relationship between cake collapse and overall cell
survival, with the object of building a clinically-viable RBC lyophilization
protocol.
PMID- 26418067
TI - Interaction of extravillous trophoblast galectin-1 and mucin(s)-Is there a
functional relevance?
AB - In the course of embryo implantation extensive interaction of the trophoblast
with uterine tissue is crucial for adequate trophoblast invasion. This
interaction is highly controlled, and it has been pointed out that a specific
glycocode and changes in glycosylation may be important for successful
implantation and maintenance of pregnancy. Both uterine and trophoblast cells
have been shown to express cell surface glycoconjugates and sugar binding
proteins, such as mucins (MUC) and galectins (gals). An increasing number of
studies have investigated potential candidates interacting in this process.
However, knowledge about the biochemical nature of the interactions and their
importance for trophoblast cell function, and, consequently, for pregnancy
outcome are still lacking. This review is aimed at deliberating the possibility
that mucins, as heavily glycosylated proteins, might be among the functionally
relevant galectin ligands in human trophoblast, based on both published data and
our original research.
PMID- 26418070
TI - A strange family, or how a new pleolipovirus reveals its friends and relatives.
AB - A new virus of halophilic Archaea is reported by Liu et al., and is remarkable in
many ways. SNJ2 is the first temperate, pleomorphic virus (pleolipovirus) that
integrates into the genome of its host. Analyses of the virus structure and its
genome have provided an unexpected puzzle while at the same time solving another.
On the one hand, the study shows a curious relationship exists between SNJ2 and
an unrelated provirus (SNJ1) found as a plasmid in the same cell. The presence of
SNJ1 appears to allow much higher levels of SNJ2 virus to be produced, although
the mechanism involved remains unclear. On the other hand, the curious occurrence
of a conserved cluster of pleolipovirus-related genes found widely distributed
among haloarchaeal genomes and known for almost 10 years, now appears to
correspond to SNJ2-related proviruses.
PMID- 26418069
TI - Elements as Direct Feedstocks for Organic Synthesis: Fe/I2/O2 for Diamination of
2-Cyclohexenones with 2-Aminopyrimidine and 2-Aminopyridines.
AB - Elements as feedstocks for organic synthesis, the trio of metallic iron,
molecular iodine, and dioxygen, were found to be an excellent tool for oxidative
regioselective diamination of conjugated enones with 2-aminopyrimidine (a
guanidine surrogate) and 2-aminopyridines leading to unaromatized coupled
products in moderate to good yields.
PMID- 26418071
TI - Microdialysis as a Part of Invasive Cerebral Monitoring During Porcine Septic
Shock.
AB - BACKGROUND: Metabolic changes in critically ill patients with endotoxin-induced
septic shock are measured primarily by techniques that afford organ-specific
metabolic monitoring based on interstitial fluid samples. The present study was
designed to evaluate the role of cerebral microdialysis (MD) as a part of
invasive neuromonitoring during endotoxemia in a porcine model. MATERIALS AND
METHODS: Continuous endotoxin infusion was administered to 7 female pigs and, in
addition to hemodynamic monitoring and blood chemistry, interstitial lactate,
pyruvate, glucose and glycerol concentrations in muscle, liver, and cerebral
tissue were measured via in vivo MD for an observation period of 180 minutes.
RESULTS: The cerebral concentrations of lactate and glycerol showed no
significant increases, whereas the hepatic and muscular levels rose dramatically
under endotoxemia. However, the lactate/pyruvate ratio and especially the
lactate/glucose ratio showed a profound and significant increase in brain tissue
as well. Cerebral perfusion pressure decreased from 77 to 50 mm Hg without
reaching pathologic values. CONCLUSIONS: Although our results confirm the special
protection of the brain during endotoxemia compared with other organs, early
metabolic changes become evident by increasing lactate/pyruvate ratio and
lactate/glucose ratio. MD appears to be a suitable additional technique in
invasive neuromonitoring for obtaining early information about metabolic
deterioration in the brain during septic shock.
PMID- 26418072
TI - Combined use of simulation and digital technologies for teaching dermatologic
surgery.
PMID- 26418073
TI - HCV NS3 quasispecies in liver and plasma and dynamics of telaprevir-resistant
variants in breakthrough patients assessed by UDPS: A case study.
AB - BACKGROUND: The impact of pre-existing variants in hepatitis C virus (HCV)
quasispecies, carrying resistance-associated mutations (RAMs), on the outcome of
treatment with direct acting antiviral agents (DAA) is debated and it is
complicated by the lack of knowledge of quasispecies distribution between the
viral reservoir (liver) and the circulating compartment. OBJECTIVE: To evaluate
NS3 protease heterogeneity and presence of RAMs on baseline plasma and liver
biopsy samples. Plasma dynamics were also analyzed during therapy and after its
suspension. Study design Ultra-deep pyrosequencing (UDPS) was performed in two
HCV genotype 1a patients who received telaprevir (TVR)-based therapy and
developed treatment failure due to TVR-resistance. RESULTS: In both patients the
baseline diversity of NS3 quasispecies in plasma was higher than in liver
(183.6*10(-4) vs 47.8*10(-4) and 246.0*10(-4) vs 55.0*10(-4) nt
substitution/site, respectively, p<0.0001), but phylogenetic trees did not
evidence compartmentalization between the two compartments. At baseline RAMs
(i.e. V36A, T54A) were detected very low levels (range: 0.31-0.52%) in both
specimen types. However, phylogenetic analyses revealed that the viral variants
carrying these mutations at baseline were different from those that became fixed
at breakthrough, when combined V36M+R155K, conferring high-level resistance to
TVR, were observed. The frequency of resistance-associated variants declined
after withdrawal of drug selective pressure. CONCLUSIONS: UDPS allowed extensive
evaluation of quasispecies compartmentalization and of their dynamics after
withdrawal of TVR. Plasma and liver NS3 quasispecies, including low level RAMs,
do not show significant difference.
PMID- 26418074
TI - Comparison of the clinical impact of endoscopic ultrasound-guided
choledochoduodenostomy and hepaticogastrostomy for bile duct obstruction with
duodenal obstruction.
PMID- 26418075
TI - Co-heredity of silent CAP + 1570 T>C (HBB:c*96T>C) defect and severe beta-thal
mutation: a cause of mild beta-thalassemia intermedia.
AB - INTRODUCTION: During an intensive screening program aimed at identifying the
healthy carriers of thalassemia and the couples at risk of bearing an affected
fetus, a rare single nucleotide variation (SNV), CAP + 1570 T > C (HBB:c*96T >
C), located 12 nucleotides upstream of the polyadenylation signal in 3'UTR of the
beta globin gene was identified. It was previously reported as a beta+
thalassemia mutation and later as a plain polymorphism. METHODS: Genotype
identification of globin gene mutations was carried out using sequencing
analysis, GAP-PCR, and MLPA methods. RESULTS: CAP + 1570 T > C (HBB:c*96T > C)
was found in 39 heterozygotes, in one case in homozygous state and in thirteen
cases of co-inheritance of this nucleotide substitution with other mutations in
globin genes. Carriers of this mutation showed a 'silent' phenotype without
appreciable microcytosis and hypochromia, so they cannot be differentiated from
noncarrier individuals. Compound heterozygotes for this mutation and severe beta
thal mutations showed a variable phenotype ranging from beta-thal carrier to mild
form of beta-thalassemia intermedia, revealing new aspects and allowing to better
understand the clinical implications of this nucleotide substitution that can be
classified as a silent beta-thalassemic defect. CONCLUSION: Data reported in this
study indicate the need of investigating partner of beta-thalassemia carrier by
complete sequencing analysis of beta-globin gene and of providing an appropriate
genetic counseling for couples at risk undergoing prenatal diagnosis.
PMID- 26418076
TI - Impact of serum Wisteria floribunda agglutinin positive Mac-2-binding protein and
serum interferon-gamma-inducible protein-10 in primary biliary cirrhosis.
AB - AIM: We aimed to examine the relationship between serum Wisteria floribunda
agglutinin positive Mac-2-binding protein (WFA(+) -M2BP) levels and serum
interferon-gamma-inducible protein-10 (IP-10) levels and liver histological
findings for patients with primary biliary cirrhosis (PBC) compared with other
laboratory fibrotic or inflammatory parameters. METHODS: A total of 57 PBC
patients were analyzed. Receiver-operator curve (ROC) analysis was performed for
calculating the area under the ROC (AUROC) for WFA(+) -M2BP, IP-10 and four serum
fibrosis markers for the presence of liver cirrhosis (F4) or advanced fibrosis
(F3 or F4). Similarly, ROC analysis of WFA(+) -M2BP, IP-10, aspartate
aminotransferase and alanine aminotransferase for the presence of severe
inflammation activity (A3) was performed. RESULTS: There were eight men and 49
women (median age, 59 years). As for histological findings, F4 was observed in
five patients, F3 in 11, F2 in 17, F1 in 24 and F0 in zero, whereas A3 was
observed in seven patients, A2 in 27, A1 in 19 and A0 in four. The WFA(+) -M2BP
levels ranged from 0.5 cut-off index (COI) to 13.6 COI (median, 1.8), while serum
IP-10 levels ranged 121.9-1835.9 pg/mL (median, 571.5). For predicting liver
cirrhosis, WFA(+) -M2BP yielded the highest AUROC (0.97, P < 0.01). For
predicting severe liver inflammation activity (A3), WFA(+) -M2BP and serum IP-10
yielded the highest AUROC with a level of 0.87. WFA(+) -M2BP levels significantly
correlated with serum IP-10 levels (rs = 0.55, P < 0.0001). CONCLUSION: Serum
WFA(+) -M2BP and serum IP-10 can be useful markers for predicting histological
findings in PBC patients.
PMID- 26418077
TI - Ethnic and socioeconomic disparities in dermatology.
AB - Ethnic and socioeconomic disparities exist within healthcare. Specifically,
minority group members experience more deleterious health outcomes than do
majority group members. In this paper, we explore the factors that influence such
variety, with a focus on the field of dermatology, in an attempt to understand
the ways to improve minority group results. We also highlight how the prevalence
of mental health issues within minority group and low socioeconomic status
individuals can differentially influence dermatological disease states, such as
the relationship between depression and psoriasis.
PMID- 26418078
TI - C-H Oxidation of Ingenanes Enables Potent and Selective Protein Kinase C Isoform
Activation.
AB - Ingenol derivatives with varying degrees of oxidation were prepared by two-phase
terpene synthesis. This strategy has allowed access to analogues that cannot be
prepared by semisynthesis from natural ingenol. Complex ingenanes resulting from
divergent C-H oxidation of a common intermediate were found to interact with
protein kinase C in a manner that correlates well with the oxidation state of the
ingenane core. Even though previous work on ingenanes has suggested a strong
correlation between potential to activate PKCdelta and induction of neutrophil
oxidative burst, the current study shows that the potential to activate PKCbetaII
is of key importance while interaction with PKCdelta is dispensable. Thus, key
modifications of the ingenane core allowed PKC isoform selectivity wherein
PKCdelta-driven activation of keratinocytes is strongly reduced or even absent
while PKCbetaII-driven activation of neutrophils is retained.
PMID- 26418079
TI - Generally applicable limits on intakes of uranium based on its chemical toxicity
and the radiological significance of intakes at those limits.
AB - Uranium is chemically toxic and radioactive, and both considerations have to be
taken into account when limiting intakes of the element, in the context of both
occupational and public exposures. Herein, the most recent information available
on the chemical toxicity and biokinetics of uranium is used to propose new
standards for limiting intakes of the element. The approach adopted allows
coherent standards to be set for ingestion and inhalation of different chemical
forms of the element by various age groups. It also allows coherent standards to
be set for occupational and public exposures (including exposures of different
age groups) and for various exposure regimes (including short-term and chronic
exposures). The proposed standards are more restrictive than those used
previously, but are less restrictive than the Minimal Risk Levels proposed
recently by the US Agency for Toxic Substances and Disease Registry. Having
developed a set of proposed limits based solely on chemical toxicity
considerations, the radiological implications of exposure at those proposed
limits are investigated for natural, depleted and enriched uranium.
PMID- 26418080
TI - High Mobility Ambipolar Diketopyrrolopyrrole-Based Conjugated Polymer Synthesized
Via Direct Arylation Polycondensation.
AB - A diketopyrrolopyrrole-based conjugated polymer, PDPP-4FTVT, which exhibits
ambipolar transport behavior in air with hole and electron mobilities up to 3.40
and 5.86 cm(2) V(-1) s(-1), respectively, is synthesized via direct arylation
polycondensation. Incorporation of F-atoms in beta-positions of thiophene rings
dramatically improves the efficiency of direct arylation polycondensation.
PMID- 26418082
TI - Pressure Control of Cuprophilic Interactions in a Luminescent Mechanochromic
Copper Cluster.
AB - For the development of applications based on mechanochromic luminescent
materials, a comprehensive study of the mechanism responsible for the emission
changes is required. We report the study of a mechanochromic copper iodide
cluster under hydrostatic pressure, which allows control of crystal packing via
modification of the intermolecular interactions. In situ single-crystal powder X
ray diffraction analysis and emission measurements under pressure permit one to
establish a direct correlation between the molecular structure and luminescence
properties and, in particular, to demonstrate that cuprophilic interactions are
responsible for the stimuli-responsive luminescence properties of such
multinuclear coordination compounds.
PMID- 26418083
TI - Diet-Quality Scores and Prevalence of Nonalcoholic Fatty Liver Disease: A
Population Study Using Proton-Magnetic Resonance Spectroscopy.
AB - Dietary pattern analysis is an alternative approach to examine the association
between diet and nonalcoholic fatty liver disease (NAFLD). This study examined
the association of two diet-quality scores, namely Diet Quality Index
International (DQI-I) and Mediterranean Diet Score (MDS) with NAFLD prevalence.
Apparently healthy Chinese adults (332 male, 465 female) aged 18 years or above
were recruited through a population screening between 2008 and 2010 in a cross
sectional population-based study in Hong Kong. DQI-I and MDS, as well as major
food group and nutrient intakes were calculated based on dietary data from a food
frequency questionnaire. NAFLD was defined as intrahepatic triglyceride content
at >=5% by proton-magnetic resonance spectroscopy. Multivariate logistic
regression models were used to examine the association between each diet-quality
score or dietary component and prevalent NAFLD with adjustment for potential
lifestyle, metabolic and genetic factors. A total of 220 subjects (27.6%) were
diagnosed with NAFLD. DQI-I but not MDS was associated with the prevalence of
NAFLD. A 10-unit decrease in DQI-I was associated with 24% increase in the
likelihood of having NAFLD in the age and sex adjusted model (95% CI: 1.06-1.45,
p = 0.009), and the association remained significant when the model was further
adjusted for other lifestyle factors, metabolic and genetic factors [OR: 1.26
(95% CI: 1.03-1.54), p = 0.027]. Multivariate regression analyses showed an
inverse association of the intake of vegetables and legumes, fruits and dried
fruits, as well as vitamin C with the NAFLD prevalence (p<0.05). In conclusion, a
better diet quality as characterized by a higher DQI-I and a higher consumption
of vegetables, legumes and fruits was associated with a reduced likelihood of
having NAFLD in Hong Kong Chinese.
PMID- 26418084
TI - The metabolic and cardiovascular consequences of obesity in persons with HIV on
long-term antiretroviral therapy.
AB - OBJECTIVE: This study assessed the effect of obesity on metabolic and
cardiovascular disease risk factors in HIV-infected adults on antiretroviral
therapy with sustained virologic suppression. DESIGN: Observational, comparative
cohort study with three group-matched arms: 35 nonobese and 35 obese HIV-infected
persons on efavirenz, tenofovir and emtricitabine with plasma HIV-1 RNA less
than 50 copies/ml for more than 2 years, and 30 obese HIV-uninfected controls.
Patients did not have diabetes or known cardiovascular disease. METHODS: We
compared glucose tolerance, serum lipids, brachial artery flow-mediated dilation,
carotid intima-media thickness, and soluble inflammatory and vascular adhesion
markers between nonobese and obese HIV-infected patients, and between obese HIV
infected and HIV-uninfected patients, using Wilcoxon rank-sum tests and
multivariate linear regression. RESULTS: The cohort was 52% men and 48% nonwhite.
Nonobese and obese HIV-infected patients did not differ by clinical or
demographic characteristics. Obese HIV-uninfected controls were younger than
obese HIV-infected patients and less likely to smoke (P < 0.03 for both). Among
HIV-infected patients, obesity was associated with greater insulin release, lower
insulin sensitivity, and higher serum high-sensitivity C-reactive protein,
interleukin-6, and tumor necrosis factor-alpha receptor 1 levels (P < 0.001), but
similar lipid profiles, sCD14, sCD163, intercellular adhesion molecule 1 and
vascular cell adhesion molecule 1, and carotid intima-media thickness and flow
mediated dilation. In contrast, Obese HIV-infected patients had adverse lipid
changes, and greater circulating intercellular adhesion molecule 1, vascular cell
adhesion molecule 1 and sCD14, compared with obese HIV-uninfected controls after
adjusting for age and other factors. CONCLUSION: Obesity impairs glucose
metabolism and contributes to circulating high-sensitivity C-reactive protein,
interleukin-6, and tumor necrosis factor-alpha receptor 1 levels, but has few
additive effects on dyslipidemia and endothelial activation, in Obese HIV
infected adults on long-term antiretroviral therapy.
PMID- 26418085
TI - Postautologous stem cell transplantation long-term outcomes in 26 HIV-positive
patients affected by relapsed/refractory lymphoma.
AB - OBJECTIVES: To describe survival data, CD4 T-cell long-term dynamics and the
correlation between dynamics and events occurrence in 26 HIV-positive patients
with refractory lymphoma in complete response after autologous stem cell
transplantation (ASCT). DESIGN: Retrospective single-centre study. METHODS:
Lymphoma relapse, second cancers and opportunistic infections were considered
after ASCT. Group A included patients experiencing events after ASCT and group B
the remaining patients. Overall survival, progression-free survival and event
free survival probabilities were estimated by Kaplan-Meier method. The comparison
of median CD4 T-cell count at cancer diagnosis with matched values was
investigated by Wilcoxon signed-rank test and between group A and B by Mann
Whitney U test. RESULTS: With a median of 6-year follow-up, the overall survival,
the progression-free survival and the event-free survival at 10 years were 91, 86
and 36%. Compared with CD4 T-cell count at cancer diagnosis a higher amount was
maintained over time after ASCT. Two patients experienced a lymphoma relapse at
4.3 and 3.1 years; five patients had secondary malignancies and nine patients
opportunistic infections at a median time of 2.2 and 0.4 years from ASCT. At 6
and 12 months after ASCT, a significant difference in CD4 T-cell count was found
between group A and B. CONCLUSION: ASCT has a dramatic impact on survival of HIV
positive patients with refractory lymphoma. We support surveillance of
opportunistic infections early after ASCT and of second cancers or lymphoma
relapses later from ASCT. Both opportunistic infections and second malignancies
were successfully managed and the only long-term death occurred due to lymphoma
relapse. ASCT seems to contribute to immune recovery.
PMID- 26418087
TI - An expanding universe of noncoding RNAs between the poles of basic science and
clinical investigations.
AB - The Keystone Symposium 'MicroRNAs and Noncoding RNAs in Cancer', Keystone, CO,
USA, 7-12 June 2015 Since the discovery of RNAi, great efforts have been
undertaken to unleash the potential biomedical applicability of small noncoding
RNAs, mainly miRNAs, involving their use as biomarkers for personalized
diagnostics or their usability as active agents or therapy targets. The
research's focus on the noncoding RNA world is now slowly moving from a phase of
basic discoveries into a new phase, where every single molecule out of many
hundreds of cataloged noncoding RNAs becomes dissected in order to investigate
these molecules' biomedical relevance. In addition, RNA classes neglected before,
such as long noncoding RNAs or circular RNAs attract more attention. Numerous
timely results and hypotheses were presented at the 2015 Keystone Symposium
'MicroRNAs and Noncoding RNAs in Cancer'.
PMID- 26418088
TI - The Effect of Salinity on Egg Development and Viability of Schistocephalus
solidus (Cestoda: Diphyllobothriidea).
AB - Schistocephalus solidus plerocercoids commonly infect three-spined stickleback
Gasterosteus aculeatus populations in brackish and freshwaters, but infections
are typically absent from marine populations. Here we provide an experimental
test of the salinity tolerance of S. solidus eggs, to determine the role of
salinity in limiting the distribution of infection in coastal zones. We find that
S. solidus eggs, derived from the in vitro culture of 3 different plerocercoids,
developed normally in salinities of up to 12.50/00, but above this egg viability
dropped rapidly, and no egg hatching was observed at salinities above 200/00. Our
results are consistent with the distribution of infections in natural stickleback
populations and add resolution to previous descriptive observations on salinity
tolerance in S. solidus. They also demonstrate that S. solidus presents a novel
disease challenge to marine populations of three-spined sticklebacks entering
brackish and freshwater environments.
PMID- 26418086
TI - HIV transmission biology: translation for HIV prevention.
AB - Rigorous testing of new HIV-prevention strategies is a time-consuming and
expensive undertaking. Thus, making well informed decisions on which candidate
prevention approaches are most likely to provide the most benefit is critical to
appropriately prioritizing clinical testing. In the case of biological
interventions, the decision to test a given prevention approach in human trials
rests largely on evidence of protection in preclinical studies. The ability of
preclinical studies to predict efficacy in humans may depend on how well the
model recapitulates key biological features of HIV transmission relevant to the
question at hand. Here, we review our current understanding of the biology of HIV
transmission based on data from animal models, cell culture, and viral sequence
analysis from human infection. We summarize studies of the bottleneck in viral
transmission; the characteristics of transmitted viruses; the establishment of
infection; and the contribution of cell-free and cell-associated virus. We seek
to highlight the implications of HIV-transmission biology for development of
prevention interventions, and to discuss the limitations of existing preclinical
models.
PMID- 26418089
TI - [The political dimension of open access: knowledge as a public good or as a
commodity?].
PMID- 26418090
TI - [Is disease merely illness?: Biomedicine, "parallel" forms of care and power].
AB - Following Giovanni Berlinguer's proposal that health/disease processes are one of
the primary spies into the contradictions of a system, this article describes
cases that occurred in central and peripheral capitalist contexts as well as in
the so-called "real socialist" States that allow such a role to be seen.
Secondly, we observe the processes and above all the interpretations developed in
Latin America and especially Mexico regarding the role attributed to traditional
medicine in the identity and sense of belonging of indigenous peoples, which
emphasize the incompatibility of indigenous worldviews with biomedicine. To do so
we analyze projects that were carried out under the notion of intercultural
health, which in large part resulted in failure both in health and political
terms. The almost entirely ideological content and perspective of these projects
is highlighted, as is the scant relationship they hold with the reality of
indigenous people. Lastly, the impact and role that the advance of these
conceptualizations and health programs might have had in the disengagement
experienced over the last nearly ten years in the ethnic movements of Latin
America is considered.
PMID- 26418091
TI - [Religion and health: the public intervention of Catholic religious agents
trained in bioethics in the parliamentary debate on death with dignity in
Argentina].
AB - This paper discusses from a sociological perspective one of Catholicism's fronts
of public intervention in the development and enactment of health legislation. In
particular we analyze the debate in parliamentary committees on the so-called
"death with dignity" law (No. 26742), for which a group of bioethics experts was
convened to counsel senators regarding the scope and limits of the law. The
majority of the invited experts advocated a personalist bioethics perspective,
which is a theological bioethics development of contemporary Catholicism. In the
debate no representatives of other faiths were present, reinforcing the widely
studied overlap between Catholicism and politics in Argentina.
PMID- 26418092
TI - [Body, rights and comprehensive health: Analysis of the parliamentary debates on
the Gender Identity and Assisted Fertilization Laws (Argentina, 2011-2013)].
AB - In this paper we present an analysis of the parliamentary debates of the Gender
Identity Law (No. 26743) and the Assisted Fertilization Law (No. 26862) carried
out in the Argentine National Congress between 2011 and 2013. Using a qualitative
content analysis technique, the stenographic records of the debates were analyzed
to explore the following questions: How was the public problem to which each law
responds characterized? How was the mission of each law conceptualized? To what
extent did those definitions call into question ideas of health and illness, in
including in the public health system coverage for certain medical treatments of
body optimization or modification? In the process of sanctioning both laws, the
concepts of health and disease were put into dispute as moral categories. In this
context, an expanded concept of comprehensive health arose, in which desires
regarding reproduction and the body were included.
PMID- 26418093
TI - [Women, addiction and rehabilitation: Reflections from the northwestern border of
Mexico].
AB - Since the recognition of addiction as a mental illness, studies concerning
treatment and therapeutic models have tended to focus on its psychiatric and
psychological dimensions. The aim of this article is to highlight the centrality
of the social dimension, not only as potential trigger of addictive behaviors and
of stigma regarding these behaviors, but also as a variable that permeates
diagnosis and treatment. The reflections are based on fieldwork carried out in
rehabilitation centers for drug-consuming women in the border city of Tijuana,
northwestern Mexico. The results show that the predominant therapeutic models in
the city are based in and reproduce the traditional role of women. The social
implications of this finding are analyzed, and it is suggested that these centers
could be better utilized in the process of building a society with greater gender
equality.
PMID- 26418094
TI - [Cartography of psychoactive heterotopias: a look at the medical, legal and
social discourses regarding drug use].
AB - This article traces a map of the social control of drugs through the politics of
space, according to the Foucaultian concept of "heterotopia." Firstly, a brief
genealogy of the use of psychotropic substances in different times and cultures
is described, up to the introduction of the prohibitionist paradigm. Attention is
paid to the way in which power has marked, separated and enclosed certain rituals
and uses of pleasure in physical and symbolic sites. The itinerary is focused on
the Spanish context to establish a dialogue between the various policies of space
that have come into being and have overlapped in the construction and management
of a problem which has been rendered an object to the gazes, mechanics and
discourses of the medical, legal, and social fields. In this way, the
intersections between the liminal spaces of drug use and the harm reduction
paradigm are analyzed, including therapeutic strategies with prescribed drugs,
from methadone programs to the new heroin programs.
PMID- 26418095
TI - [Deaths due to motorcycle accidents and their association with variables related
to social reproduction in a northeastern Brazilian state].
AB - The objective of this article was to identify the association between motorcycle
deaths and variables related to Samaja's theory of social reproduction in the
period 2000-2005 in the state of Pernambuco. An ecological, case-control study
was carried out, with municipalities as the unit of analysis. Cases were defined
as the 20% of municipalities with the highest local empirical Bayesian
coefficients for mortality due to motorcycle accidents, and controls as the 40%
with the lowest coefficients. The municipalities with the greatest chances of
high coefficients for mortality due to motorcycle accidents showed high
population growth factors and increases in the total fleet of motorcycles, with
low population densities, low GDP per capita, and more than 20 motorcycles per
thousand inhabitants. We conclude that the variables related to macro-policies
proved to have greater force in explaining higher chances of motorcycle death.
PMID- 26418096
TI - [Level of and change in road traffic mortality in Argentina, Chile, Colombia and
Mexico, 2000-2011].
AB - The aim of this study was to estimate the effect of run-over fatalities and
traffic collisions in life expectancy in Argentina, Chile, Colombia and Mexico,
between 2000 and 2011. Years of life expectancy lost (YLEL) were calculated for
the periods 2000-2002 and 2009-2011. The results show that road traffic deaths
made up between 1% and 4% of all deaths in each country. In the first period, the
highest level of mortality occurred in Colombia (YLEL=0.96) and the lowest in
Argentina (YLEL=0.59). In all the countries studied except Argentina, the impact
of these deaths on life expectancy was reduced in the second period. The main
change took place in Colombia, reaching 0.72 YLEL in the second period. It is
concluded that traffic-related deaths have a negative impact on health systems,
victims, the productive sector, and society in general. From this point of view,
the issue of road transit must be considered a matter of public health, requiring
multi-sector intervention in the design of national and regional policies.
PMID- 26418097
TI - [The perception of values in food commercials on the part of young people with
and without eating disorders].
AB - Advertising uses stereotyped body images to promote physical ideals and unhealthy
eating habits related to food products which are targeted especially at young
people. The purpose of this study, carried out in Barcelona (Spain) in May 2013,
was to test the perception of 139 young people of university age - with and
without eating disorders - regarding 25 values in seven food commercials that did
and did not use body image strategies. Results show that only the group of young
people with eating disorders considered commercials using body image strategies
to have a very negative influence on values such as health, well-being, family
and effort. In contrast, the assessment of the two groups regarding the rest of
the commercials greatly coincided. These results show that today?s university
youth have accepted as normal a beauty canon based on the prevailing social and
economic order, while young people in treatment for eating disorders have learned
to denaturalize such messages.
PMID- 26418098
TI - [Care work in the health sector based on the psychodynamics of work and the care
perspective: An interview with Pascale Molinier].
AB - This interview with Pascale Molinier was carried out in Buenos Aires in October
2014, in the context of activities organized by the Health and Work Program at
the Department of Community Health of the Universidad Nacional de Lanus,
Argentina. The interview explores the relationship between work and
subjectivation, examining the role of work in the structuring of the psyche, in
the dynamics of pleasure and suffering, and in the construction of gender
identities. "Feminized" work - that of nurses, caregivers and maids, among others
- is examined from a "care" perspective, analyzing its intrinsic invisibility and
impossibility of being quantified and measured, which makes it a challenge to
management-based logic.
PMID- 26418099
TI - Is It Possible to Draw a Risk Map for Obturator Nerve Injury During Pelvic Lymph
Node Dissection? The Heilbronn Experience and a Review of the Literature.
AB - OBJECTIVE: Obturator nerve injury (ONI) is a rare complication during pelvic
lymph node dissection (PLND), in extraperitoneal laparoscopic radical
prostatectomy (e-LRP), and/or extraperitoneal robotic-assisted laparoscopic
radical prostatectomy (e-RALP). It is important to recognize ONI during the
initial operation, maximizing the feasibility of simultaneous repair. Here we
report our experience with ONI during e-LRP/e-RALP procedures and draw an injury
risk map. MATERIALS AND METHODS: Between December 1999 and November 2014, 2531 e
LRPs and 1027 e-RALPs were performed. Five patients (3 during e-LRP, 2 during e
RALP) experienced ONI in the proximal part of the nerve. Obturator nerves were
clipped during the 3 e-LRP cases. Clips were immediately removed, and patients
received physiotherapy with medical treatments in the postoperative period.
During e-RALP, two obturator nerves were transected and subsequently repaired
using the robotic Da Vinci((r)) Surgical System (Intuitive Surgical, Inc.,
Sunnyvale, CA). ONI types were investigated in detail in these patients, and
current published studies were analyzed in order to draw a risk map. RESULTS:
Mean follow-up was 18.8 +/- 2.7 months. In total, 3558 cases (2531 e-LRPs, 1027 e
RALPs) were performed. ONI occurred in 3 e-LRP (0.1%) and 2 e-RALP (0.1%)
patients. Simultaneous repair was performed successfully in all cases, as clips
were removed in e-LRP cases and obturator nerves were repaired using 6/0
polypropylene (Prolene((r)); Ethicon, Somerville, NJ) suture in e-RALP cases.
There was no complication associated with obturator nerve functions such as
adductor function and/or neurologic deficiency during long-term follow-up. In
view of published studies in the literature, the proximal part of the obturator
nerve is at highest risk for injury during PLND, representing 77.8% of reported
cases of ONI. CONCLUSIONS: According to our ONI risk map, the proximal part of
the obturator nerve is at higher risk for injury during PLND. Careful dissection
and a good knowledge of pelvic anatomy are essential for preventing ONI.
Successful ONI management can be performed simultaneously in experienced hands.
PMID- 26418100
TI - Adsorption of poly acrylic acid onto the surface of calcite: an experimental and
simulation study.
AB - Macromolecular binding to minerals is of great importance in the formation of
biofilms, and carboxylate functional groups have been found to play a pivotal
role in the functioning of these macromolecules. Here we present both
fluorescence time-resolved anisotropy measurements and simulation data on the
conformational behaviour and binding of a poly acrylic acid polymer. In solution
the polymer exhibits a pH dependent behaviour, with a coiled conformation at a
low pH and extended conformation at higher pH values. The polymer is readily
adsorbed on the surface of calcite, preferring to bind in an extended
conformation, with the strength of the adsorption dependent on the pH and
presence of counter ions. We discuss the reasons why the calculated adsorption
free energy differs from that obtained from a Langmuir isotherm analysis, showing
that they refer to different quantities. The enhanced binding of the extended
conformations shows the importance of flexibility in the binding of
macromolecules.
PMID- 26418101
TI - Potent Antibacterial Activity of Copper Embedded into Silicone and Polyurethane.
AB - A simple, easily up-scalable swell-encapsulation-shrink technique was used to
incorporate small 2.5 nm copper nanoparticles (CuNPs) into two widely used
medical grade polymers, polyurethane, and silicone, with no significant impact on
polymer coloration. Both medical grade polymers with incorporated CuNPs
demonstrated potent antimicrobial activity against the clinically relevant
bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. CuNP
incorporated silicone samples displayed potent antibacterial activity against
both bacteria within 6 h. CuNP-incorporated polyurethane exhibited more
efficacious antimicrobial activity, resulting in a 99.9% reduction in the numbers
of both bacteria within just 2 h. With the high prevalence of hospital-acquired
infections, the use of antimicrobial materials such as these CuNP-incorporated
polymers could contribute to reducing microbial contamination associated with
frequently touched surfaces in and around hospital wards (e.g., bed rails,
overbed tables, push plates, etc.).
PMID- 26418102
TI - A Conversation With the Winner of the Clara Ford Nursing Excellence Award.
PMID- 26418104
TI - Cardiac Assessment.
AB - Heart disease remains the number one cause of mortality in both men and women in
the United States and patients with heart failure are at high risk for
hospitalization. Thirty-day readmission rates have become a benchmark for
hospitals and home healthcare agency reimbursement. Physical exam and history
taking are essential to evaluate patients with suspected or known heart disease,
and to detect early symptoms of worsening heart failure. Home care clinicians
have the opportunity to assess the patient in the home environment, identify
significant changes in the patient's status, and form a plan of care for
effective intervention to prevent the need for emergency department care or
rehospitalization. In this second article of a four-part series, the subjective
and objective assessment of the cardiovascular system exam is reviewed.
PMID- 26418106
TI - Suicide Risk in Homebound Elderly Individuals What Home Care Clinicians Need to
Know.
AB - Suicide rates and risk increase with age. Older people are heavy users of in-home
services. Many of the reasons that older adults need home care are serious risk
factors for suicide. These include disability, physical illness, and other
conditions that affect self-sufficiency. Home care providers are well positioned
to identify elder suicide risk. This requires some understanding of suicidal
behavior, the key risk factors for suicide in elders, the warning signs, and what
to do if suicidality is encountered. The suicide prevention field has not
recognized home care as a means of reaching suicidal elders. It is critical that
this be corrected as elder suicides stand to rise as the elder population
increases.
PMID- 26418107
TI - Best Practice for After-Hours Hospice Symptom Management: A Literature Review.
AB - Medicare-certified hospice home care agencies must provide a 24/7 on-call system
to respond to patient and caregiver concerns. How these calls are handled impacts
patient and family outcomes and satisfaction. Ideally, hospice nurses provide
adequate caregiver education during routine visits to minimize the need for after
hours calls. A literature review provided evidence that hospice nurse education
and appropriate telephone support improves symptom management, enhances family
support, provides a sense of security, reduces anxiety, and promotes comfort.
PMID- 26418108
TI - Managing Sjogren's Syndrome.
AB - There are approximately 4 million Americans diagnosed with Sjogren's Syndrome.
This article discusses the epidemiology, pathophysiology, diagnostics, and
implications for home care clinicians who may encounter patients with this
syndrome. Chronic pain is discussed as well as interventions to manage symptoms
such fatigue, dry eyes mouth and skin.
PMID- 26418109
TI - Medication Discrepancies and Associated Risk Factors Identified in Home Health
patients.
AB - Medication discrepancies can place patients at increased risk for adverse drug
events. We sought to determine the frequency, type, and reason for medication
discrepancies in patients receiving home healthcare following hospital discharge.
We conducted a retrospective, observational study of adults discharged from an
academic medical center who received home healthcare following hospital discharge
from one affiliated home healthcare agency. Medication discrepancies were
identified by comparing the hospital discharge medication list to what the
patient was taking at the first home healthcare visit. Almost all patients
(66/70, 94%) had at least one medication discrepancy. The median number of
discrepancies per patient was 5. Nearly half of the discrepancies were omissions
(46%), in which the patient was not taking a medication on the discharge
medication list. Increased age was significantly associated with fewer medication
discrepancies overall (IRR = 0.99, p < 0.05). Higher health literacy was
associated with more omissions (IRR = 1.85, p < 0.05).
PMID- 26418110
TI - Retinopathy Overview.
PMID- 26418111
TI - As U-500 Insulin Safety Concerns Mount, It's Time to Rethink Safe Use of
Strengths Above U-100.
PMID- 26418112
TI - Scabies Infestation.
PMID- 26418113
TI - A Day in the Life of a Community Health Worker in Uganda.
PMID- 26418114
TI - Communicating With Deaf Patients: What You Need to Know.
PMID- 26418115
TI - Staying Within the Law: Home Healthcare Billing and Documentation.
PMID- 26418116
TI - The Need for Increased Home-Based Primary Care Visits.
PMID- 26418117
TI - Light-Controlled Histone Deacetylase (HDAC) Inhibitors: Towards
Photopharmacological Chemotherapy.
AB - Cancer treatment suffers from limitations that have a major impact on the
patient's quality of life and survival. In the case of chemotherapy, the systemic
distribution of cytotoxic drugs reduces their efficacy and causes severe side
effects due to nonselective toxicity. Photopharmacology allows a novel approach
to address these problems because it employs external, local activation of
chemotherapeutic agents by using light. The development of photoswitchable
histone deacetylase (HDAC) inhibitors as potential antitumor agents is reported
herein. Analogues of the clinically used chemotherapeutic agents vorinostat,
panobinostat, and belinostat were designed with a photoswitchable azobenzene
moiety incorporated into their structure. The most promising compound exhibits
high inhibitory potency in the thermodynamically less stable cis form and a
significantly lower activity for the trans form, both in terms of HDAC activity
and proliferation of HeLa cells. This approach offers a clear prospect towards
local photoactivation of HDAC inhibition to avoid severe side effects in
chemotherapy.
PMID- 26418118
TI - Hierarchical Mesoporous/Macroporous Perovskite La0.5Sr0.5CoO3-x Nanotubes: A
Bifunctional Catalyst with Enhanced Activity and Cycle Stability for Rechargeable
Lithium Oxygen Batteries.
AB - Perovskites show excellent specific catalytic activity toward both oxygen
reduction reaction (ORR) and oxygen evolution reaction (OER) in alkaline
solutions; however, small surface areas of the perovskites synthesized by
traditional sol-gel methods lead to low utilization of catalytic sites, which
gives rise to poor Li-O2 batteries performance and restricts their application.
Herein, a hierarchical mesporous/macroporous perovskite La0.5Sr0.5CoO3-x (HPN
LSC) nanotube is developed to promote its application in Li-O2 batteries. The HPN
LSC nanotubes were synthesized via electrospinning technique followed by
postannealing. The as-prepared HPN-LSC catalyst exhibits outstanding intrinsic
ORR and OER catalytic activity. The HPN-LSC/KB electrode displays excellent
performance toward both discharge and charge processes for Li-O2 batteries, which
enhances the reversibility, the round-trip efficiency, and the capacity of
resultant batteries. The synergy of high catalytic activity and hierarchical
mesoporous/macroporous nanotubular structure results in the Li-O2 batteries with
good rate capability and excellent cycle stability of sustaining 50 cycles at a
current density of 0.1 mA cm(-2) with an upper-limit capacity of 500 mAh g(-1).
The results will benefit for the future development of high-performance Li-O2
batteries using hierarchical mesoporous/macroporous nanostructured perovskite
type catalysts.
PMID- 26418119
TI - Joint myocardial T1 and T2 mapping using a combination of saturation recovery and
T2 -preparation.
AB - PURPOSE: To develop a heart-rate independent breath-held joint T1 -T2 mapping
sequence for accurate simultaneous estimation of coregistered myocardial T1 and
T2 maps. METHODS: A novel preparation scheme combining both a saturation pulse
and T2 -preparation in a single R-R interval is introduced. The time between
these two pulses, as well as the duration of the T2 -preparation is varied in
each heartbeat, acquiring images with different T1 and T2 weightings, and no
magnetization dependence on previous images. Inherently coregistered T1 and T2
maps are calculated from these images. Phantom imaging is performed to compare
the proposed maps with spin echo references. In vivo imaging is performed in ten
subjects, comparing the accuracy and precision of the proposed technique to
existing myocardial T1 and T2 mapping sequences of the same duration. RESULTS:
Phantom experiments show that the proposed technique provides accurate
quantification of T1 and T2 values over a wide-range (T1 : 260 ms to 1460 ms, T2
: 40 ms to 200 ms). In vivo imaging shows that the proposed sequence quantifies
T1 and T2 values similar to a saturation-based T1 mapping and a conventional
breath-hold T2 mapping sequence, respectively. CONCLUSION: The proposed sequence
allows joint estimation of accurate and coregistered quantitative myocardial T1
and T2 maps in a single breath-hold. Magn Reson Med 76:888-896, 2016. (c) 2015
Wiley Periodicals, Inc.
PMID- 26418122
TI - Does vagotomy reduce the risk of Parkinson's disease?
PMID- 26418120
TI - Correction: Short-term Forecasting of the Prevalence of Trachoma: Expert Opinion,
Statistical Regression, versus Transmission Models.
PMID- 26418123
TI - Metabolic routes along digestive system of licorice: multicomponent sequential
metabolism method in rat.
AB - This study was conducted to establish the multicomponent sequential metabolism
(MSM) method based on comparative analysis along the digestive system following
oral administration of licorice (Glycyrrhiza uralensis Fisch., leguminosae), a
traditional Chinese medicine widely used for harmonizing other ingredients in a
formulae. The licorice water extract (LWE) dissolved in Krebs-Ringer buffer
solution (1 g/mL) was used to carry out the experiments and the comparative
analysis was performed using HPLC and LC-MS/MS methods. In vitro incubation, in
situ closed-loop and in vivo blood sampling were used to measure the LWE
metabolic profile along the digestive system. The incubation experiment showed
that the LWE was basically stable in digestive juice. A comparative analysis
presented the metabolic profile of each prototype and its corresponding
metabolites then. Liver was the major metabolic organ for LWE, and the metabolism
by the intestinal flora and gut wall was also an important part of the process.
The MSM method was practical and could be a potential method to describe the
metabolic routes of multiple components before absorption into the systemic blood
stream. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26418125
TI - The Risk of Acute Kidney Injury from Fluid Restriction and Hydroxyethyl Starch in
Thoracic Surgery.
AB - BACKGROUND: Fluid is restricted in thoracic surgery to reduce acute lung injury,
and hydroxyethyl starches (HES) are often administered to reduce fluid amount.
This strategy may contribute to the development of acute kidney injury (AKI). We
evaluated the incidence, risk factors, and prognosis of AKI in thoracic surgery.
We especially focused on whether fluid restriction/HES administration increased
AKI. METHODS: This is a retrospective study of patients undergoing thoracic
surgery in a tertiary care academic center. Postoperative AKI was diagnosed
within 72 hours after surgery based on the Acute Kidney Injury Network criteria.
Demographic, intraoperative, and postoperative data were compared between non-AKI
and AKI groups. Logistic regression was used to model the association between
risk factors and AKI. RESULTS: Final analysis included 1442 patients. Of these,
74 patients developed AKI (5.1%). Crystalloid restriction (<=3 mL.kg.h) was
unrelated to AKI, regardless of preoperative renal functions (odds ratio [OR],
0.5; 95% confidence interval [CI] 0.2-1.4). AKI occurred more often when HES were
administered to the patients with decreased renal function (OR, 7.6; 95% CI, 1.5
58.1) or having >2 risk factors with normal renal function (OR, 7.2; 95% CI, 3.6
14.1). Multivariate analysis revealed several risk factors: angiotensin
converting enzyme inhibitor/angiotensin receptor blockers, open thoracotomy,
pneumonectomy/esophagectomy, diabetes mellitus, cerebrovascular disease, low
albumin level, and decreased renal function. CONCLUSIONS: Fluid restriction
neither increased nor was a risk factor for AKI. HES should be administered with
caution in high-risk patients undergoing thoracic surgery.
PMID- 26418124
TI - Inhibition of Mitochondrial Fission Protein Reduced Mechanical Allodynia and
Suppressed Spinal Mitochondrial Superoxide Induced by Perineural Human
Immunodeficiency Virus gp120 in Rats.
AB - BACKGROUND: Mitochondria play an important role in many cellular and physiologic
functions. Mitochondria are dynamic organelles, and their fusion and fission
regulate cellular signaling, development, and mitochondrial homeostasis. The most
common complaint of human immunodeficiency virus (HIV)-sensory neuropathy is pain
on the soles in patients with HIV, but the exact molecular mechanisms of HIV
neuropathic pain are not clear. In the present study, we investigated the role of
mitochondrial dynamin-related protein 1 (Drp1, a GTPase that mediates
mitochondrial fission) in the perineural HIV coat glycoprotein gp120-induced
neuropathic pain state. METHODS: Neuropathic pain was induced by the application
of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. Mechanical
threshold was tested using von Frey filaments. The mechanical threshold response
was assessed over time using the area under curves. Intrathecal administration of
antisense oligodeoxynucleotide (ODN) against Drp1, mitochondrial division
inhibitor-1 (mdivi-1), or phenyl-N-tert-butylnitrone (a reactive oxygen species
scavenger) was given. The expression of spinal Drp1 was examined using western
blots. The expression of mitochondrial superoxide in the spinal dorsal horn was
examined using MitoSox imaging. RESULTS: Intrathecal administration of either
antisense ODN against Drp1 or mdivi-1 decreased mechanical allodynia (a sensation
of pain evoked by nonpainful stimuli) in the gp120 model. Intrathecal ODN or
mdivi-1 did not change basic mechanical threshold in sham surgery rats.
Intrathecal Drp1 antisense ODN decreased the spinal expression of increased Drp1
protein induced by peripheral gp120 application. Intrathecal phenyl-N-tert
butylnitrone reduced mechanical allodynia. Furthermore, both intrathecal Drp1
antisense ODN and mdivi-1 reversed the upregulation of mitochondrial superoxide
in the spinal dorsal horn in the gp120 neuropathic pain state. CONCLUSIONS: These
data suggest that mitochondrial division plays a substantial role in the HIV
gp120-related neuropathic pain state through mitochondrial reactive oxygen
species and provides evidence for a novel approach to treating chronic pain in
patients with HIV.
PMID- 26418127
TI - Talking about Climate Change and Global Warming.
AB - The increasing prevalence of social networks provides researchers greater
opportunities to evaluate and assess changes in public opinion and public
sentiment towards issues of social consequence. Using trend and sentiment
analysis is one method whereby researchers can identify changes in public
perception that can be used to enhance the development of a social consciousness
towards a specific public interest. The following study assessed Relative search
volume (RSV) patterns for global warming (GW) and Climate change (CC) to
determine public knowledge and awareness of these terms. In conjunction with
this, the researchers looked at the sentiment connected to these terms in social
media networks. It was found that there was a relationship between the awareness
of the information and the amount of publicity generated around the terminology.
Furthermore, the primary driver for the increase in awareness was an increase in
publicity in either a positive or a negative light. Sentiment analysis further
confirmed that the primary emotive connections to the words were derived from the
original context in which the word was framed. Thus having awareness or knowledge
of a topic is strongly related to its public exposure in the media, and the
emotional context of this relationship is dependent on the context in which the
relationship was originally established. This has value in fields like
conservation, law enforcement, or other fields where the practice can and often
does have two very strong emotive responses based on the context of the problems
being examined.
PMID- 26418126
TI - Intraoperative Electroencephalogram Suppression Predicts Postoperative Delirium.
AB - BACKGROUND: Postoperative delirium is a common complication associated with
increased morbidity and mortality, longer hospital stays, and greater health care
expenditures. Intraoperative electroencephalogram (EEG) slowing has been
associated previously with postoperative delirium, but the relationship between
intraoperative EEG suppression and postoperative delirium has not been
investigated. METHODS: In this observational cohort study, 727 adult patients who
received general anesthesia with planned intensive care unit admission were
included. Duration of intraoperative EEG suppression was recorded from a frontal
EEG channel (FP1 to F7). Delirium was assessed twice daily on postoperative days
1 through 5 with the Confusion Assessment Method for the intensive care unit.
Thirty days after surgery, quality of life, functional independence, and
cognitive ability were measured using the Veterans RAND 12-item survey, the
Barthel index, and the PROMIS Applied Cognition-Abilities-Short Form 4a survey.
RESULTS: Postoperative delirium was observed in 162 (26%) of 619 patients
assessed. When we compared patients with no EEG suppression with those divided
into quartiles based on duration of EEG suppression, patients with more
suppression were more likely to experience delirium (chi(4) = 25, P < 0.0001).
This effect remained significant after we adjusted for potential confounders
(odds ratio for log(EEG suppression) 1.22 [99% confidence interval, 1.06-1.40, P
= 0.0002] per 1-minute increase in suppression). EEG suppression may have been
associated with reduced functional independence (Spearman partial correlation
coefficient -0.15, P = 0.02) but not with changes in quality of life or cognitive
ability. Predictors of EEG suppression included greater end-tidal volatile
anesthetic concentration and lower intraoperative opioid dose. CONCLUSIONS: EEG
suppression is an independent risk factor for postoperative delirium. Future
studies should investigate whether anesthesia titration to minimize EEG
suppression decreases the incidence of postoperative delirium. This is a substudy
of the Systematic Assessment and Targeted Improvement of Services Following
Yearlong Surgical Outcomes Surveys (SATISFY-SOS) surgical outcomes registry
(NCT02032030).
PMID- 26418128
TI - Home-based versus clinic-based specimen collection in the management of Chlamydia
trachomatis and Neisseria gonorrhoeae infections.
AB - BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the
most frequent causes of bacterial sexually transmitted infections (STIs).
Management strategies that reduce losses in the clinical pathway from infection
to cure might improve STI control and reduce complications resulting from lack
of, or inadequate, treatment. OBJECTIVES: To assess the effectiveness and safety
of home-based specimen collection as part of the management strategy for
Chlamydia trachomatis and Neisseria gonorrhoeae infections compared with clinic
based specimen collection in sexually-active people. SEARCH METHODS: We searched
the Cochrane Sexually Transmitted Infections Group Specialized Register, the
Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and
LILACS on 27 May 2015, together with the World Health Organization International
Clinical Trials Registry (ICTRP) and ClinicalTrials.gov. We also handsearched
conference proceedings, contacted trial authors and reviewed the reference lists
of retrieved studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) of
home-based compared with clinic-based specimen collection in the management of C.
trachomatis and N. gonorrhoeae infections. DATA COLLECTION AND ANALYSIS: Three
review authors independently assessed trials for inclusion, extracted data and
assessed risk of bias. We contacted study authors for additional information. We
resolved any disagreements through consensus. We used standard methodological
procedures recommended by Cochrane. The primary outcome was index case
management, defined as the number of participants tested, diagnosed and treated,
if test positive. MAIN RESULTS: Ten trials involving 10,479 participants were
included. There was inconclusive evidence of an effect on the proportion of
participants with index case management (defined as individuals tested, diagnosed
and treated for CT or NG, or both) in the group with home-based (45/778, 5.8%)
compared with clinic-based (51/788, 6.5%) specimen collection (risk ratio (RR)
0.88, 95% confidence interval (CI) 0.60 to 1.29; 3 trials, I2 = 0%, 1566
participants, moderate quality). Harms of home-based specimen collection were not
evaluated in any trial. All 10 trials compared the proportions of individuals
tested. The results for the proportion of participants completing testing had
high heterogeneity (I2 = 100%) and were not pooled. We could not combine data
from individual studies looking at the number of participants tested because the
proportions varied widely across the studies, ranging from 30% to 96% in home
group and 6% to 97% in clinic group (low-quality evidence). The number of
participants with positive test was lower in the home-based specimen collection
group (240/2074, 11.6%) compared with the clinic-based group (179/967, 18.5%) (RR
0.72, 95% CI 0.61 to 0.86; 9 trials, I2 = 0%, 3041 participants, moderate
quality). AUTHORS' CONCLUSIONS: Home-based specimen collection could result in
similar levels of index case management for CT or NG infection when compared with
clinic-based specimen collection. Increases in the proportion of individuals
tested as a result of home-based, compared with clinic-based, specimen collection
are offset by a lower proportion of positive results. The harms of home-based
specimen collection compared with clinic-based specimen collection have not been
evaluated. Future RCTs to assess the effectiveness of home-based specimen
collection should be designed to measure biological outcomes of STI case
management, such as proportion of participants with negative tests for the
relevant STI at follow-up.
PMID- 26418129
TI - Liquid Crystal Interfaces Programmed with Enzyme-Responsive Polymers and
Surfactants.
AB - Synthesis of biologically active peptide-polymer amphiphiles (PPAs), and
characterization of assemblies formed by PPAs at the interfaces of liquid crystal
(LC) microdroplets, is shown to permit the use of PPAs in strategies that can
trigger ordering transitions in LC microdroplets in response to targeted
biomolecular events.
PMID- 26418131
TI - Reply.
PMID- 26418132
TI - A clinical evaluation of skin disorders of lower limb amputation sites.
AB - Amputee patients commonly experience skin problems that may result in social,
mental, and economic difficulties. The purpose of this study was to evaluate the
incidence of dermatological disorders and identify potential causes and
symptomatic patterns among a population of lower limb amputees. Seventy lower
limb amputees were enrolled. Complete examinations were performed by a
dermatologist, who diagnosed and documented any skin disorders observed and
recorded demographic characteristics of each patient. Mycological and
bacteriological swabs were collected from the skin at the amputation site for
culture analysis. In patients with suspected disease, patch tests were performed.
Of the 70 patients, 58 (82.9%) were male and 12 (17.1%) female. Vascular
insufficiency due to diabetes (n = 38, 54.3%) and trauma (n = 16, 22.9%) were the
most common reasons for amputation. Skin problems were observed in 49 (70%)
cases, and positive allergen reactions occurred in 16 (45.7%) of the 35 contact
dermatitis cases. Fungal infection occurred in two patients and bacterial
infection in seven. Seventy percent of the lower limb amputee patients in this
cohort exhibited skin problems. This high percentage indicates that skin problems
may reduce patients' quality of life. A multidisciplinary approach to the
treatment of patients who have undergone amputation and early recognition and
treatment of symptoms are therefore of critical importance.
PMID- 26418130
TI - Chromatin Remodeling Factor Brg1 Supports the Early Maintenance and Late
Responsiveness of Nestin-Lineage Adult Neural Stem and Progenitor Cells.
AB - Insights from embryonic development suggest chromatin remodeling is important in
adult neural stem cells (aNSCs) maintenance and self-renewal, but this concept
has not been fully explored in the adult brain. To assess the role of chromatin
remodeling in adult neurogenesis, we inducibly deleted Brg1--the core subunit of
SWI/SNF-like Brg1/Brm-associated factor chromatin remodeling complexes--in nestin
expressing aNSCs and their progeny in vivo and in culture. This resulted in
abnormal adult neurogenesis in the hippocampus, which initially reduced
hippocampal aNSCs and progenitor maintenance, and later reduced its
responsiveness to physiological stimulation. Mechanistically, deletion of Brg1
appeared to impair cell cycle progression, which is partially due to elevated p53
pathway and p21 expression. Knockdown of p53 rescued the neurosphere growth
defects caused by Brg1 deletion. Our results show that epigenetic chromatin
remodeling (via a Brg1 and p53/p21-dependent process) determines the aNSCs and
progenitor maintenance and responsiveness of neurogenesis.
PMID- 26418134
TI - The road to the winner's circle begins at the ASHRM Annual Conference!
AB - The saying "Time flies when you're having fun" is a time-honored expression that
is part of our vernacular. Sometimes we say it in jest, tongue in cheek, when it
seems a long day will never end! However, when we celebrate professional or
personal anniversaries, when we look at our growing kids, or especially, when we
look in the mirror, we marvel at how fast the years have flown by!
PMID- 26418135
TI - Delivering safe and trusted healthcare-Patient-centered and value-based.
PMID- 26418133
TI - Osteodystrophy in Cholestatic Liver Diseases Is Attenuated by Anti-gamma-Glutamyl
Transpeptidase Antibody.
AB - BACKGROUND: Cholestatic liver diseases exhibit higher levels of serum gamma
glutamyl transpeptidase (GGT) and incidence of secondary osteoporosis. GGT has
been identified as a novel bone-resorbing factor that stimulates osteoclast
formation. The aim of this study was to elucidate the interaction of elevated GGT
levels and cholestatic liver disease-induced bone loss. METHODS: Wistar rats were
divided into three groups: sham-operated control (SO) rats, bile duct ligation
(BDL) rats, and anti-GGT antibody-treated BDL rats (AGT). Serum GGT level was
measured. Bone mineral density (BMD) was analyzed by dual-energy X-ray
absorptiometry. Bone morphometric parameters and microarchitectural properties
were determined by micro-computed tomography and histomorphometry of the distal
metaphysis of femurs. Alterations of bone metabolism-related factors were
evaluated by cytokine array. Effects of GGT on osteoblasts or stromal cells were
evaluated by RT-PCR, enzyme activity, and mineralization ability. RESULTS: Serum
levels of GGT were significantly elevated in the BDL-group. In the BDL group,
BMD, bone mass percentage, and osteoblast number were significantly decreased,
whereas osteoclast number was significantly increased. These alterations were
markedly attenuated in the AGT group. The mRNA levels of vascular endothelial
growth factor-A, LPS-induced CXC chemokine, monocyte chemoattractant protein-1,
tumor necrosis factor-alpha interleukin-1beta and receptor activator of nuclear
factor-kappa B ligand were upregulated, and those of interferon-gamma and
osteoprotegerin were downregulated in the GGT-treated stromal cells. Furthermore,
GGT inhibited mineral nodule formation and expression of alkaline phosphatase and
bone sialo-protein in osteoblastic cells. CONCLUSION: Our results indicate that
elevated GGT level is involved in hepatic osteodystrophy through secretion of
bone resorbing factor from GGT-stimulated osteoblasts/bone marrow stromal cells.
In addition, GGT also possesses suppressive effects on bone formation. Managing
elevated GGT levels by anti-GGT antibody may become a novel therapeutic agent for
hepatic osteodystrophy in chronic liver diseases.
PMID- 26418136
TI - Where we've been, where we are, and where we are going: A 35-year perspective on
healthcare risk management.
AB - In celebration of ASHRM's 35-year anniversary, this article will explore the
journey of healthcare risk management and the professionals practicing within its
discipline over time and project the future of both the discipline and the
profession.
PMID- 26418137
TI - How is the effectiveness of root cause analysis measured in healthcare?
AB - If a hundred healthcare executives were polled about their definitions of root
cause analysis, there would be a hundred different answers. Herein lies the
problem-understanding the intent and power of root cause analysis (RCA). For this
reason, RCA is viewed as having either limited or phenomenal value to an
organization. This article will seek to strip away the labels associated with RCA
brands and focus on the processes, their results, and how they are communicated
(or miscommunicated) to executive management. Effective RCA efforts can fail
because of their inability to demonstrate their value to the bottom line of the
organization.
PMID- 26418138
TI - Business resilience: Reframing healthcare risk management.
AB - The responsibility of risk management in healthcare is fractured, with multiple
stakeholders. Most hospitals and healthcare systems do not have a fully
integrated risk management system that spans the entire organizational and
operational structure for the delivery of key services. This article provides
insight toward utilizing a comprehensive Business Resilience program and
associated methodology to understand and manage organizational risk leading to
organizational effectiveness and operational efficiencies, with the fringe
benefit of realizing sustainable operational capability during adverse
conditions.
PMID- 26418139
TI - The role of informed consent in patient complaints: Reducing hidden health system
costs and improving patient engagement through shared decision making.
AB - INTRODUCTION: Patient complaints about physicians are strongly associated with
malpractice risk. Physicians at high risk for lawsuits tend to have poor
communication skills and are more commonly the subject of patient complaints
about communication issues. If a malpractice action does not arise, patient
complaints nonetheless represent significant prelitigation transaction costs for
the healthcare system that have not been previously quantified. Informed consent
complaints represent a unique constellation of clinical communication skills
clearly tied to malpractice risk. The goal of this study was to measure
institutional resource consumption allocated to informed consent (IC) complaints,
which are both costly and preventable. METHODS: We compared IC complaints to
other complaints about medical care in a single medical center in the United
States, estimating the absolute and relative burden of IC deficiencies within
this healthcare system. RESULTS: Resource consumption for the resolution of IC
complaints far exceeded their proportional representation of complaints,
representing half of all complaints, while disproportionately absorbing two
thirds of staff time devoted to complaint resolution. CONCLUSIONS: Complaint
resolution represents an unrecognized remediable cost and an underappreciated
opportunity for reducing waste in healthcare. We suggest that healthcare systems
can reduce costs and elevate their patient-centered care practices by improving
patient-provider communication during medical decision making via engagement
strategies such as shared decision making.
PMID- 26418140
TI - Case law update.
PMID- 26418141
TI - Multiprobe devices for exercise transcutaneous oxymetry in patients complaining
claudication: interest and limits of unusual probe positions.
AB - BACKGROUND: Exercise transcutaneous oximetry (PtcO2) can argue for a vascular
origin of exercise-related pain in atypical unusual localizations, such as
lumbar, thigh or foot pain. We used five probes as a standard for treadmill PtcO2
tests. Recent commercially available devices now include up to eight probes. We
aimed at analyzing the potential interest of positioning a 6th probe on the area
of unusual localization during exercise PtcO2 tests. METHODS: We retrospectively
analyzed our data with a 6-probes device, using as a standard: one probe on the
chest, one on each buttock and one on each calf. The sixth probe was positioned
either: in the lumbar median position (N.=342), on the anterior lower part of the
thigh (N.=391) or on the dorsum of the foot (N.=155) in patients complaining
exercise-induced pain including the back, thigh or foot respectively. Results on
the sixth probe at the limb were compared to result of the standard adjacent
probe. A positive test (abnormal result) was defined as a minimal value of the
DROP-index lower than minus 15 mmHg. RESULTS: Prevalence of positive results on
the 6th probe with negative results on the adjacent standard probe was 2.3% at
the lumbar site, 3.8% at the thigh and 12.3% at the foot level. CONCLUSIONS:
Atypical localizations are rarely but sometimes associated to isolated positive
exercise PtcO2 results and may justify the use of more than five probes in some
patients, specifically for foot pain.
PMID- 26418142
TI - Endovascular therapy for visceral artery aneurysms.
AB - BACKGROUND: The aim of this study was to report outcome and complications of
endovascular therapy for visceral artery aneurysms (VAA). METHODS: Forty
endovascular procedures for VAAs were performed in 33 patients between 2009 and
2014. RESULTS: The main indications was size (N.=15), bleeding (N.=14) and
mycotic aneurysm (N.=3). The splenic artery was the most common artery of true
aneurysms (11/16) and pseudo aneurysms due to pancreatitis (5/14). The median
size of the true aneurysms was 24 mm (range 15-65). Two ruptures of true VAAs
occurred in elderly. Five patients had eleven synchronous artery aneurysms at CT
abdomen. Local anesthesia was used in 93%. Coil embolization were performed
without (N.=15) and with (N.=14) other techniques. Nine aneurysms were excluded
with stent grafts and patency rate was 88%. Coil embolization was complicated by
five spleen infarctions, managed with splenectomy (N.=1) and drainage of abscess
(N.=1). One patient died, unrelated to the VAA. CONCLUSIONS: Endovascular therapy
of VAAs, irrespective of etiology, was an effective treatment option.
PMID- 26418143
TI - Endovenous laser ablation of the great saphenous vein comparing 1920-nm and 1470
nm diode laser.
AB - BACKGROUND: The aim of this study was to compare venous occlusion rates at a one
year follow-up comparing 1920-nm versus 1470-nm endolaser. METHODS: Randomized
prospective study with consecutive patients with varicose veins associated to
great saphenous reflux. The 1470-nm laser ablation was performed in continuous
mode, with power of 10 W, while for the 1920-nm it was set in 5 W. Follow-up data
were collected at the 7-day, 30-day, 3-month, 6-month and 1-year visits, and
involved clinical, ultrasound evaluation and measurement of occlusion length.
RESULTS: Sixty seven patients were included, with 42 limbs operated in the 1470
nm group and 48 limbs in the 1920-nm group. There were no differences in relation
to age, CEAP (Clinical, Etiologic, Anatomical and Pathological Classification),
VCSS (Venous Clinical Severity Score) and saphenous diameter. The resulting LEED
in 1920-nm group was 17.8+/-0.6 J/cm and vs. 24.7+/-0.8 J/cm in 1470-nm group
(P<0.01). Closure rates were lower for the 1920-nm group: 90.9% vs. 96.8%
(P=0.06) at 30 days, 87.5% vs. 96.3% at 6 months (P=0.03), and 87.5% vs. 94.7%
(P=0.05) at one year. The 1920-nm group had less ecchymosis (18.7% vs. 52.4%),
induration (12.4% vs. 38.1%) and days of analgesic use (1.4+/-0.2 vs. 2.4+/-0.4).
CEAP and VCSS were reduced over time in both groups. CONCLUSIONS: Treatment with
endolaser 1920-nm was feasible and with reduced complications. The use of low
endoluminal energy resulted in lower vein occlusion rates comparing to the 1470
nn laser. Clinical outcome scores were similar between groups.
PMID- 26418145
TI - Update on medical abortion: simplifying the process for women.
AB - PURPOSE OF REVIEW: Medical abortion using mifepristone and misoprostol comprises
a growing proportion of abortions performed in the United States. Simplifying the
process of medical abortion can optimize use of resources and improve care for
women. RECENT FINDINGS: Medical abortion using evidence-based protocols is
effective through 70 days' gestation. The requirement of a follow-up office visit
with a transvaginal ultrasound to ensure completion of medical abortion is safely
and effectively replaced with self-administered low-sensitivity or
semiquantitative urine pregnancy tests and remote communication with women. Most
contraceptive options can be initiated the same day as mifepristone
administration to improve contraceptive use after medical abortion. State
legislatures continue to pass laws that threaten evidence-based medical abortion
practices. Such efforts ultimately limit access to well-tolerated and effective
medical abortion services. SUMMARY: Research supports simplification of the
follow-up protocol for medical abortion, and provision of the contraceptive
implant and progestin injectable for postabortion contraception the same day as
mifepristone administration. With disregard to its documented safety and
efficacy, legislative challenges persist as significant challenges to provision
of evidence-based medical abortion.
PMID- 26418146
TI - Speech in 10-Year-Olds Born With Cleft Lip and Palate: What Do Peers Say?
AB - OBJECTIVE: The aim of this study was to explore how 10-year-olds describe speech
and communicative participation in children born with unilateral cleft lip and
palate in their own words, whether they perceive signs of velopharyngeal
insufficiency (VPI) and articulation errors of different degrees, and if so,
which terminology they use. Methods/Participants: Nineteen 10-year-olds
participated in three focus group interviews where they listened to 10 to 12
speech samples with different types of cleft speech characteristics assessed by
speech and language pathologists (SLPs) and described what they heard. The
interviews were transcribed and analyzed with qualitative content analysis.
RESULTS: The analysis resulted in three interlinked categories encompassing
different aspects of speech, personality, and social implications: descriptions
of speech, thoughts on causes and consequences, and emotional reactions and
associations. Each category contains four subcategories exemplified with quotes
from the children's statements. More pronounced signs of VPI were perceived but
referred to in terms relevant to 10-year-olds. Articulatory difficulties, even
minor ones, were noted. Peers reflected on the risk to teasing and bullying and
on how children with impaired speech might experience their situation. The SLPs
and peers did not agree on minor signs of VPI, but they were unanimous in their
analysis of clinically normal and more severely impaired speech. CONCLUSIONS:
Articulatory impairments may be more important to treat than minor signs of VPI
based on what peers say.
PMID- 26418147
TI - Age and Phonetic Influences on Velar Flutter as a Component of Nasal Turbulence
in Children With Repaired Cleft Palate.
AB - OBJECTIVE: The purpose of this study was to determine the influence of age and
selected phonetic factors on velar flutter as a component of nasal turbulence in
children with repaired cleft palate. PARTICIPANTS: A total of 30 children with
repaired cleft palate with or without cleft lip ranging in age from 4 to 13 years
(mean, 8.6 years; standard deviation, 2.4 years) who exhibited nasal turbulence
characterized by velar flutter participated in the study. MEASURES: The headset
of a nasometer was used to record the children producing multiple repetitions of
consonant-vowel (CV) syllables that contrasted the stops /p/ and /t/ with the
fricatives /f/ and /s/ and the high-front vowel /i/ with the low mid-central
vowel /Lambda/. All targeted consonants were coded relative to the presence of
flutter using both perceptual and spectral criteria. Percentages of syllables
coded for flutter were calculated as a function of consonant and vowel types.
Intra-and interjudge reliability of coding was high. RESULTS: Percentages of
syllables with velar flutter ranged from a high of 100% to a low of 4% among the
participants. A Spearman rank-order correlation between age and percentage of
syllables with flutter was nonsignificant. Mantel-Haenszel tests for repeated
measures indicated that flutter occurred more often during production of
syllables containing /i/ (62%) when compared with /Lambda/ (50%) (P = .029).
CONCLUSIONS: Velar flutter as a component of nasal turbulence varies widely among
children with repaired cleft palate. CV syllables with high vowels appear to
trigger velar flutter more often than syllables with low vowels.
PMID- 26418144
TI - Regulation and Function of the Nucleotide Binding Domain Leucine-Rich Repeat
Containing Receptor, Pyrin Domain-Containing-3 Inflammasome in Lung Disease.
AB - Inflammasomes are specialized inflammatory signaling platforms that govern the
maturation and secretion of proinflammatory cytokines, such as IL-1beta and IL
18, through the regulation of caspase-1-dependent proteolytic processing. Several
nucleotide binding domain leucine-rich repeat-containing receptor (NLR) family
members (i.e., NLR family, pyrin domain containing [NLRP] 1, NLRP3, and NLR
family, caspase recruitment domain containing-4 [NLRC4]) as well as the pyrin and
hemopoietic expression, interferon-inducibility, nuclear localization domain
containing family member, absent in melanoma 2, can form inflammasome complexes
in human cells. In particular, the NLRP3 inflammasome is activated in response to
cellular stresses through a two-component pathway, involving Toll-like receptor 4
ligand interaction (priming) followed by a second signal, such as ATP-dependent
P2X purinoreceptor 7 receptor activation. Emerging studies suggest that the NLRP3
inflammasome can exert pleiotropic effects in human diseases with potentially
both pro- and antipathogenic sequelae. Whereas NLRP3 inflammasome activation can
serve as a vital component of host defense against invading bacteria and
pathogens, excessive activation of the inflammasome can lead to inflammation
associated tissue injury in the setting of chronic disease. In addition,
pyroptosis, an inflammasome-associated mode of cell death, contributes to host
defense. Recent research has described the regulation and function of the NLRP3
inflammasome in various pulmonary diseases, including acute lung injury and acute
respiratory distress syndrome, sepsis, respiratory infections, chronic
obstructive pulmonary disease, asthma, pulmonary hypertension, cystic fibrosis,
and idiopathic pulmonary fibrosis. The NLRP3 and related inflammasomes, and their
regulated cytokines or receptors, may represent novel diagnostic or therapeutic
targets in pulmonary diseases and other diseases in which inflammation
contributes to pathogenesis.
PMID- 26418148
TI - Facial Asymmetry in Children with Unicoronal Synostosis Who Have Undergone
Craniofacial Reconstruction in Infancy.
AB - OBJECTIVE: Quantitatively assess 3D spatially detailed soft-tissue facial
asymmetry in children who had undergone craniofacial reconstruction for
Unicoronal Synostosis (UCS), and compare the facial asymmetry to control
patients. It was hypothesized that there would be no significant differences in
the facial asymmetry between the groups. DESIGN: Clinical, retrospective follow
up study. Methodological study. SETTING: Primary care center.
PATIENTS/PARTICIPANTS: Twenty-two children with UCS were selected after review of
records. INCLUSION CRITERIA: isolated UCS; surgically treated for UCS within the
first 19 months of life, without secondary reconstruction; and DNA analysis for
the Muenke mutation. An age- and sex-matched control group was employed.
INTERVENTIONS: The UCS group had undergone bilateral craniotomy of the frontal
bone with unilateral supraorbital rim advancement. MAIN OUTCOME MEASURE(S): Using
3D surface scanning, a detailed map of 3D asymmetry presenting the amount of
asymmetry in the sagittal, vertical, and transverse directions was calculated for
six facial subregions. RESULTS: The facial asymmetry in the UCS group was
significantly larger than in the control group for all regions, to the largest
extent in the sagittal direction (level of significance: 5%). The regions with
the most pronounced asymmetry were cheeks (mean: 5.45 mm; SD: 1.83 mm), forehead
(mean: 5.00 mm; SD: 1.57 mm), and eyes (mean: 4.26 mm; SD: 1.44 mm). CONCLUSIONS:
Ninety percent of the UCS patients in the study had significant facial asymmetry
throughout the facial area. The study demonstrates a methodology of facial
asymmetry quantification well suited for soft-tissue surgical outcome evaluations
and long-term follow-up studies in patients with craniofacial anomalies.
PMID- 26418149
TI - Craniofacial Morphology in Midline Cervical Cleft: Case Report and Review of
Literature.
AB - Congenital midline cervical cleft is a rare anomaly of the neck. This paper
presents the case of a boy diagnosed with this disorder in which a preliminary
orthodontic treatment was implemented. The craniofacial anomalies associated with
this malformation produced a defect that could only be successfully treated
through the implementation of orthodontic and surgical treatments. In this case,
congenital midline cervical cleft was accompanied by certain disorders within the
facial structures of the skull, primarily mandibular retrusion, flattening of the
contour of the mandibular base, and a steep angle between the cranial base and
the mandibular plane.
PMID- 26418150
TI - A Qualitative Study of Children's Perspectives on Their Peer Relationships in the
Context of Living With a Craniofacial Anomaly.
AB - OBJECTIVE: To gain understanding of perspectives on peer relationships from
children with congenital craniofacial anomalies (CFA). DESIGN: This was
qualitative research based in a phenomenological approach, using narratives that
captured children's responses to open-ended and objective questions about peer
relations and life with a CFA. Interviews were audio recorded and transcribed.
Transcripts were coded according to thematic categories. SETTING: Children were
patients at a reconstructive plastic surgery center in an urban hospital and
medical school and were recruited from a regional support organization for
families of children with CFA that was associated with the hospital. PATIENTS,
PARTICIPANTS: Nine children with congenital CFA aged 9 to 14 years. MAIN OUTCOME
MEASURES: Thematic coding categories were developed from the narratives using an
open coding strategy; these categories focused on aspects of children's
interactions with peers and their appraisals of the role of their CFA in their
lives. RESULTS: Children reported satisfaction with most aspects of their peer
relationships and expressed confidence in their ability to manage challenges.
They acknowledged some difficulties with living with a CFA but tended to hold a
balanced perspective on the impact of a CFA on their lives, and they expressed
optimism about their future lives. CONCLUSIONS: This sample of children with CFA
exhibited much resilience. Although they may not be representative of all
children with CFA, they provide examples that can be used to generate hypotheses
for future research.
PMID- 26418151
TI - Update: Non-Invasive Positive Pressure Ventilation in Chronic Respiratory Failure
Due to COPD.
AB - Long-term non-invasive positive pressure ventilation (NPPV) has widely been
accepted to treat chronic hypercapnic respiratory failure arising from different
etiologies. Although the survival benefits provided by long-term NPPV in
individuals with restrictive thoracic disorders or stable, slowly-progressing
neuromuscular disorders are overwhelming, the benefits provided by long-term NPPV
in patients with chronic obstructive pulmonary disease (COPD) remain under
question, due to a lack of convincing evidence in the literature. In addition,
long-term NPPV reportedly failed in the classic trials to improve important
physiological parameters such as arterial blood gases, which might serve as an
explanation as to why long-term NPPV has not been shown to substantially impact
on survival. However, high intensity NPPV (HI-NPPV) using controlled NPPV with
the highest possible inspiratory pressures tolerated by the patient has recently
been described as a new and promising approach that is well-tolerated and is also
capable of improving important physiological parameters such as arterial blood
gases and lung function. This clearly contrasts with the conventional approach of
low-intensity NPPV (LI-NPPV) that uses considerably lower inspiratory pressures
with assisted forms of NPPV. Importantly, HI-NPPV was very recently shown to be
superior to LI-NPPV in terms of improved overnight blood gases, and was also
better tolerated than LI-NPPV. Furthermore, HI-NPPV, but not LI-NPPV, improved
dyspnea, lung function and disease-specific aspects of health-related quality of
life. A recent study showed that long-term treatment with NPPV with increased
ventilatory pressures that reduced hypercapnia was associated with significant
and sustained improvements in overall mortality. Thus, long-term NPPV seems to
offer important benefits in this patient group, but the treatment success might
be dependent on effective ventilatory strategies.
PMID- 26418153
TI - Correction: How Long Is Too Long in Contemporary Peer Review? Perspectives from
Authors Publishing in Conservation Biology Journals.
PMID- 26418152
TI - Deficits in hippocampal-dependent transfer generalization learning accompany
synaptic dysfunction in a mouse model of amyloidosis.
AB - Elevated beta-amyloid and impaired synaptic function in hippocampus are among the
earliest manifestations of Alzheimer's disease (AD). Most cognitive assessments
employed in both humans and animal models, however, are insensitive to this early
disease pathology. One critical aspect of hippocampal function is its role in
episodic memory, which involves the binding of temporally coincident sensory
information (e.g., sights, smells, and sounds) to create a representation of a
specific learning epoch. Flexible associations can be formed among these distinct
sensory stimuli that enable the "transfer" of new learning across a wide variety
of contexts. The current studies employed a mouse analog of an associative
"transfer learning" task that has previously been used to identify risk for
prodromal AD in humans. The rodent version of the task assesses the transfer of
learning about stimulus features relevant to a food reward across a series of
compound discrimination problems. The relevant feature that predicts the food
reward is unchanged across problems, but an irrelevant feature (i.e., the
context) is altered. Experiment 1 demonstrated that C57BL6/J mice with bilateral
ibotenic acid lesions of hippocampus were able to discriminate between two
stimuli on par with control mice; however, lesioned mice were unable to transfer
or apply this learning to new problem configurations. Experiment 2 used the
APPswe PS1 mouse model of amyloidosis to show that robust impairments in transfer
learning are evident in mice with subtle beta-amyloid-induced synaptic deficits
in the hippocampus. Finally, Experiment 3 confirmed that the same transfer
learning impairments observed in APPswePS1 mice were also evident in the Tg-SwDI
mouse, a second model of amyloidosis. Together, these data show that the ability
to generalize learned associations to new contexts is disrupted even in the
presence of subtle hippocampal dysfunction and suggest that, across species, this
aspect of hippocampal-dependent learning may be useful for early identification
of AD-like pathology.
PMID- 26418155
TI - Do Hybrid Trees Inherit Invasive Characteristics? Fruits of Corymbia torelliana X
C. citriodora Hybrids and Potential for Seed Dispersal by Bees.
AB - Tree invasions have substantial impacts on biodiversity and ecosystem
functioning, and trees that are dispersed by animals are more likely to become
invasive. In addition, hybridisation between plants is well documented as a
source of new weeds, as hybrids gain new characteristics that allow them to
become invasive. Corymbia torelliana is an invasive tree with an unusual animal
dispersal mechanism: seed dispersal by stingless bees, that hybridizes readily
with other species. We examined hybrids between C. torelliana and C. citriodora
subsp. citriodora to determine whether hybrids have inherited the seed dispersal
characteristics of C. torelliana that allow bee dispersal. Some hybrid fruits
displayed the characteristic hollowness, resin production and resin chemistry
associated with seed dispersal by bees. However, we did not observe bees foraging
on any hybrid fruits until they had been damaged. We conclude that C. torelliana
and C. citriodora subsp. citriodora hybrids can inherit some fruit characters
that are associated with dispersal by bees, but we did not find a hybrid with the
complete set of characters that would enable bee dispersal. However, around
20,000 hybrids have been planted in Australia, and ongoing monitoring is
necessary to identify any hybrids that may become invasive.
PMID- 26418154
TI - Relation between Intensity of Biocide Practice and Residues of Anticoagulant
Rodenticides in Red Foxes (Vulpes vulpes).
AB - Anticoagulant rodenticides (ARs) are commonly used to control rodent infestations
for biocidal and plant protection purposes. This can lead to AR exposure of non
target small mammals and their predators, which is known from several regions of
the world. However, drivers of exposure variation are usually not known. To
identify environmental drivers of AR exposure in non-targets we analyzed 331
liver samples of red foxes (Vulpes vulpes) for residues of eight ARs and used
local parameters (percentage of urban area and livestock density) to test for
associations to residue occurrence. 59.8% of samples collected across Germany
contained at least one rodenticide, in 20.2% of cases at levels at which
biological effects are suspected. Second generation anticoagulants (mainly
brodifacoum and bromadiolone) occurred more often than first generation
anticoagulants. Local livestock density and the percentage of urban area were
good indicators for AR residue occurrence. There was a positive association
between pooled ARs and brodifacoum occurrence with livestock density as well as
of pooled ARs, brodifacoum and difenacoum occurrence with the percentage of urban
area on administrative district level. Pig holding drove associations of
livestock density to AR residue occurrence in foxes. Therefore, risk mitigation
strategies should focus on areas of high pig density and on highly urbanized
areas to minimize non-target risk.
PMID- 26418156
TI - Seeing and Feeling Motion: Canonical Computations in Vision and Touch.
AB - While the different sensory modalities are sensitive to different stimulus
energies, they are often charged with extracting analogous information about the
environment. Neural systems may thus have evolved to implement similar algorithms
across modalities to extract behaviorally relevant stimulus information, leading
to the notion of a canonical computation. In both vision and touch, information
about motion is extracted from a spatiotemporal pattern of activation across a
sensory sheet (in the retina and in the skin, respectively), a process that has
been extensively studied in both modalities. In this essay, we examine the
processing of motion information as it ascends the primate visual and
somatosensory neuraxes and conclude that similar computations are implemented in
the two sensory systems.
PMID- 26418158
TI - Management of Home Parenteral Nutrition: A Prospective Multicenter Observational
Study.
AB - BACKGROUND: There are no specific Swiss home parenteral nutrition (HPN) data
showing patient characteristics, quality of life (QoL) and complications. The
goal of this study was to collect representative nationwide data on current adult
HPN patients in Switzerland for international comparability and benchmarking.
METHODS: This was a multicenter, nationwide, observational study. We conducted
interviews for demographics, PN characteristics, QoL and complications. The data
were assessed at baseline and after a follow-up of 3 months using a
questionnaire. RESULTS: Thirty-three adult patients were included. The most
common underlying diseases were cancer, radiation enteritis and state after
bariatric surgery, and the most prevalent indication was short bowel syndrome.
During the 3-month observation period, significant increase or stabilization of
body weight occurred in the patients, physical activity scores improved from 34.0
to 39.4 and mental scores improved from 41.9 to 46.4. HPN dependency and
traveling restrictions were of the greatest concern. Diarrhea, xerostomia and/or
thirst were frequent complaints. CONCLUSION: Anthropometric parameters and QoL
improved during the observational period in this HPN cohort. These Swiss HPN data
are prerequisite for evaluation and comparison of HPN recommendations and best
clinical practice, status of professional care instructions related to HPN
effectiveness, quality of treatment and patient safety.
PMID- 26418159
TI - Enantioselective Synthesis of Bicyclic delta-Lactones via N-Heterocyclic Carbene
Catalyzed Cascade Reaction.
AB - The N-heterocyclic carbene-catalyzed cascade reaction of enals with malonates to
give bicyclic delta-lactones was developed. The cyclopentane- and cyclohexane
fused delta-lactones with three continued stereocenters were obtained in high
yields with excellent diastereo- and high enantioselectivities.
PMID- 26418157
TI - Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial
Resolution following In Situ Labeling with Fluorescent Activity Based Probes.
AB - Gaucher disease is characterized by lysosomal accumulation of glucosylceramide
due to deficient activity of lysosomal glucocerebrosidase (GBA). In cells,
glucosylceramide is also degraded outside lysosomes by the enzyme
glucosylceramidase 2 (GBA2) of which inherited deficiency is associated with
ataxias. The interest in GBA and glucosylceramide metabolism in the brain has
grown following the notion that mutations in the GBA gene impose a risk factor
for motor disorders such as alpha-synucleinopathies. We earlier developed a beta
glucopyranosyl-configured cyclophellitol-epoxide type activity based probe (ABP)
allowing in vivo and in vitro visualization of active molecules of GBA with high
spatial resolution. Labeling occurs through covalent linkage of the ABP to the
catalytic nucleophile residue in the enzyme pocket. Here, we describe a method to
visualize active GBA molecules in rat brain slices using in vivo labeling. Brain
areas related to motor control, like the basal ganglia and motor related
structures in the brainstem, show a high content of active GBA. We also developed
a beta-glucopyranosyl cyclophellitol-aziridine ABP allowing in situ labeling of
GBA2. Labeled GBA2 in brain areas can be identified and quantified upon gel
electrophoresis. The distribution of active GBA2 markedly differs from that of
GBA, being highest in the cerebellar cortex. The histological findings with ABP
labeling were confirmed by biochemical analysis of isolated brain areas. In
conclusion, ABPs offer sensitive tools to visualize active GBA and to study the
distribution of GBA2 in the brain and thus may find application to establish the
role of these enzymes in neurodegenerative disease conditions such as alpha
synucleinopathies and cerebellar ataxia.
PMID- 26418161
TI - Attitudes in China about Crops and Foods Developed by Biotechnology.
AB - Transgenic Bt cotton has been planted in China since 1997 and, in 2009, biosafety
certificates for the commercial production of Bt rice and phytase corn were
issued by the Chinese government. The public attitude in China toward
agricultural biotechnology and genetically modified (GM) crops and foods has
received considerable attention worldwide. We investigated the attitudes of
consumers, Bt cotton farmers and scientists in China regarding GM crops and foods
and the factors influencing their attitudes. Data were collected using interview
surveys of consumer households, farmer households and scientists. A discrete
choice approach was used to elicit the purchase intentions of the respondents.
Two separate probit models were developed to examine the effect of various
factors on the choices of the respondents. Bt cotton farmers had a very positive
attitude because Bt cotton provided them with significant economic benefits.
Chinese consumers from developed regions had a higher acceptance and willingness
to pay for GM foods than consumers in other regions. The positive attitude toward
GM foods by the scientific community will help to promote biotechnology in China
in the future. Our survey emphasized that educational efforts made by government
officials, the media and scientists can facilitate the acceptance of GM
technology in China. Further educational efforts will be critical for influencing
consumer attitudes and decisions of government agencies in the future. More
effective educational efforts by government agencies and public media concerning
the scientific facts and safety of GM foods would enhance the acceptance of GM
crops in China.
PMID- 26418163
TI - Is Serum Serotonin Involved in the Bone Loss of Young Females with Anorexia
Nervosa?
AB - Recent experimental data suggest that circulating serotonin interacts with bone
metabolism, although this is less clear in humans. This study investigated
whether serum serotonin interferes with bone metabolism in young women with
anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin,
markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal
propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin,
soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its
binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal
bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry
in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF
1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly
reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum
serotonin levels were positively correlated with weight, body mass index, whole
body fat mass, leptin, and IGF-1, and negatively with CTX for the entire
population. Low serum serotonin levels are observed in patients with AN. Although
no direct link between low serum serotonin levels and bone mass was identified in
these patients, the negative relationship between serotonin and markers of bone
resorption found in all population nevertheless suggests the implication of
serotonin in bone metabolism. Impact of low serum serotonin on bone in AN
warrants further studies.
PMID- 26418160
TI - Vascular Smooth Muscle Cells Stimulate Platelets and Facilitate Thrombus
Formation through Platelet CLEC-2: Implications in Atherothrombosis.
AB - The platelet receptor CLEC-2 is involved in thrombosis/hemostasis, but its
ligand, podoplanin, is expressed only in advanced atherosclerotic lesions. We
investigated CLEC-2 ligands in vessel walls. Recombinant CLEC-2 bound to early
atherosclerotic lesions and normal arterial walls, co-localizing with vascular
smooth muscle cells (VSMCs). Flow cytometry and immunocytochemistry showed that
recombinant CLEC-2, but not an anti-podoplanin antibody, bound to VSMCs,
suggesting that CLEC-2 ligands other than podoplanin are present in VSMCs. VSMCs
stimulated platelet granule release and supported thrombus formation under flow,
dependent on CLEC-2. The time to occlusion in a FeCl3-induced animal thrombosis
model was significantly prolonged in the absence of CLEC-2. Because the internal
elastic lamina was lacerated in our FeCl3-induced model, we assume that the
interaction between CLEC-2 and its ligands in VSMCs induces thrombus formation.
Protein arrays and Biacore analysis were used to identify S100A13 as a CLEC-2
ligand in VSMCs. However, S100A13 is not responsible for the above-described VSMC
induced platelet activation, because S100A13 is not expressed on the surface of
normal VSMCs. S100A13 was released upon oxidative stress and expressed in the
luminal area of atherosclerotic lesions. Suspended S100A13 did not activate
platelets, but immobilized S100A13 significantly increased thrombus formation on
collagen-coated surfaces. Taken together, we proposed that VSMCs stimulate
platelets through CLEC-2, possibly leading to thrombus formation after plaque
erosion and stent implantation, where VSMCs are exposed to blood flow.
Furthermore, we identified S100A13 as one of the ligands on VSMCs.
PMID- 26418162
TI - A Survey of the Knowledge of Venous Thromboembolism Prophylaxis among the Medical
Staff of Intensive Care Units in North China.
AB - BACKGROUND: Guideline concordance for venous thromboembolism (VTE) prophylaxis in
critically ill patients in intensive care units (ICUs) varies across different
countries. OBJECTIVE: To explore how the medical staff of ICUs in China
comprehend and practice VTE prophylaxis. METHOD: Questionnaires comprising 39
questions and including 4 dimensions of thromboprophylaxis were administered in
ICUs in North China. RESULTS: In all, 52 ICUs at 23 tertiary hospitals in 7
Chinese provinces and municipalities were surveyed. A total of 2500
questionnaires were sent, and 1861 were returned, corresponding to a response
rate of approximately 74.4%. Of all surveyed medical staff, 36.5% of physicians
and 22.2% of nurses were aware of the guidelines in China, and 19.0% of
physicians and 9.5% of nurses comprehended the 9th edition of the guidelines of
the American College of Chest Physicians (ACCP). Additionally, 37.6% of the
medical staff chose a prophylaxis method based on the related guidelines, and
10.3% could demonstrate the exact indication for mechanical pattern application.
Worries about skin injury, difficulty with removal and discomfort during
mechanical thromboprophylaxis were cited by more than 30% of nurses, which was
significantly more frequent than for physicians (graduated compression stockings:
54.3% VS 34.1%, 60.7% VS 49%, and 59.4% VS 54%, p = 0.000; intermittent pneumatic
compression: 31% VS 22.2%, 19.2% VS 13.9%, and 37.8% VS 27.2%, p = 0.000).
CONCLUSIONS AND RELEVANCE: The knowledge of VTE prophylaxis among the medical
staff of ICUs in North China remains limited, which may lead to a lack of
standardization of VTE prophylaxis. Strengthened, standardized training may help
medical staff to improve their comprehension of the relevant guidelines and may
finally reduce the occurrence of VTE in ICUs and improve the prognosis of
critically ill patients with VTE.
PMID- 26418164
TI - Weight acceptance versus body dissatisfaction: Effects on stigma, perceived self
esteem, and perceived psychopathology.
AB - OBJECTIVE: It is unknown whether weight acceptance or body dissatisfaction impact
anti-fat stigma. Therefore, this study utilized a 2*2 between-subject
experimental design to examine of the relationship between body acceptance and
stigmatization. METHOD: Participants were university undergraduates (N=394, 70%
women, mean age=20.8 years, mean BMI=23.61 kg/m(2)) who were randomly assigned to
read vignettes describing an obese or normal-weight target described as either
accepting or not accepting of her weight. Participants completed measures of
stigma (the Fat Phobia Scale (FPS), the modified Anti-fat Attitudes Scale (AFA)),
perceived self-esteem (assessed with the modified Rosenberg Self-Esteem Scale
(RSE)), and perceived psychopathology. RESULTS: Analyses revealed significant
main effects for acceptance. Notably, targets who accepted their weight were less
stigmatized on the FPS (F(1, 354)=66.82, p<.001) and the AFA willpower subscale
(F(1, 373)=37.90, p<.001), and they were perceived as having better self esteem
(F(1, 371)=166.16, p<.001) and fewer psychological problems (F(1, 381)=123.19,
p<.001) than those who did not accept their weight. CONCLUSION: Results from this
study suggest that size acceptance, even when practiced by obese targets, was
significantly less stigmatized than body dissatisfaction and associated with
better perceived self esteem and mental health.
PMID- 26418165
TI - Single-Sided Deafness: The Effect of Cochlear Implantation on Quality of Life,
Quality of Hearing, and Working Performance.
AB - AIMS: To evaluate the effect of a cochlear implant (CI) on quality of life (QoL),
quality of hearing (QoH), and working performance in patients with single-sided
deafness (SSD). METHODS: Using specific questionnaires, we measured QoL, QoH, and
working performance in 7 SSD patients scheduled for CI surgery of the affected
ear. Sound localization and speech perception in noise were also assessed. All
questionnaires and tests were performed before the CI surgery and at 6 and 12
months after CI activation. RESULTS: The QoL, QoH, sound localization, and speech
perception in noise had improved statistically significantly after CI surgery.
Communication with co-workers became easier, and the patients were less fatigued
after the working day. CONCLUSIONS: CI clearly improves QoL, QoH, and working
performance in patients with SSD.
PMID- 26418166
TI - Stress reveals new destination for EGF receptor.
PMID- 26418167
TI - Reply.
PMID- 26418169
TI - How Severely Is DNA Quantification Hampered by RNA Co-extraction?
AB - The optional RNase digest that is part of many DNA extraction protocols is often
omitted, either because RNase is not provided in the kit or because users do not
want to risk contaminating their laboratory. Consequently, co-eluting RNA can
become a "contaminant" of unknown magnitude in a DNA extraction. We extracted DNA
from liver, lung, kidney, and heart tissues and established that 28-52% of the
"DNA" as assessed by spectrophotometry is actually RNA (depending on tissue
type). Including an RNase digest in the extraction protocol reduced 260:280
purity ratios. Co-eluting RNA drives an overestimation of DNA yield when
quantification is carried out using OD 260 nm spectrophotometry, or becomes an
unquantified contaminant when spectrofluorometry is used for DNA quantification.
This situation is potentially incompatible with the best practice guidelines for
biobanks issued by organizations such as the International Society for Biological
and Environmental Repositories, which state that biospecimens should be
accurately characterized in terms of their identity, purity, concentration, and
integrity. Consequently, we conclude that an RNase digest must be included in DNA
extractions if pure DNA is required. We also discuss the implications of
unquantified RNA contamination in DNA samples in the context of laboratory
accreditation schemes.
PMID- 26418168
TI - Total Saponin from Anemone flaccida Fr. Schmidt Prevents Bone Destruction in
Experimental Rheumatoid Arthritis via Inhibiting Osteoclastogenesis.
AB - Anemone flaccida Fr. Schmidt is used in the clinical compound prescription for
the treatment of rheumatoid arthritis (RA) in China and has the traditional use
of draining dampness, diminishing swelling, and relieving pain. Total saponins
(TS) are the characteristic components and also the main active ingredients of A.
flaccida. Previous reports indicated that TS possess anti-inflammatory and
immunoregulatory properties; however, the effects of TS on bone destruction of RA
have not been evaluated. In this study, our data first showed the therapeutic
effects of TS on severity of arthritis and arthritis progression in collagen
induced arthritis (CIA) rats. Then, by microfocal computed tomography (CT)
quantification, TS significantly increased bone mineral density, bone volume
fraction, and trabecular thickness and decreased trabecular separation of
inflamed joints both at peri-articular and extra-articular locations. TS also
diminished the level of the bone resorption marker CTX-I and simultaneously
increased the bone formation marker osteocalcin in sera of CIA rats.
Interestingly, TS prevented bone destruction by reducing the number of
osteoclasts in inflamed joints, reducing the expression of receptor activator of
nuclear factor-kappaF (RANK) ligand (RANKL) and RANK, increasing the expression
of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the
ratio of RANKL to OPG in inflamed joints and sera of CIA rats. This was further
confirmed in the co-culture system of human fibroblast-like synovial and
peripheral blood mononuclear cells. In addition, TS inhibited the levels of pro
inflammatory cytokines implicated in bone resorption, such as interleukin-1beta
(IL-1beta), tumor necrosis factor-alpha (TNFalpha), IL-6, IL-17, and IL-23 in
sera and joints. These findings offer convincing evidence that TS attenuate RA
partially by preventing both focal bone destruction and systemic bone loss. This
anti-erosive effect results in part from inhibiting osteoclastogenesis by
regulating the RANKL/RANK/OPG signaling pathway. The suppression of systemic and
local pro-osteoclastogenic cytokines by TS was also highly effective.
PMID- 26418170
TI - Law & Order, CSI, and NCIS: The Association Between Exposure to Crime Drama
Franchises, Rape Myth Acceptance, and Sexual Consent Negotiation Among College
Students.
AB - Previous research has identified that exposure to the crime drama genre lowers
rape myth acceptance and increases sexual assault prevention behaviors such as
bystander intervention. However, recent content analyses have revealed marked
differences in the portrayal of sexual violence within the top three crime drama
franchises. Using a survey of 313 college freshmen, this study explores the
influence of exposure to the three most popular crime drama franchises: Law &
Order, CSI, and NCIS. Findings indicate that exposure to the Law & Order
franchise is associated with decreased rape myth acceptance and increased
intentions to adhere to expressions of sexual consent and refuse unwanted sexual
activity; whereas exposure to the CSI franchise is associated with decreased
intentions to seek consent and decreased intentions to adhere to expressions of
sexual consent. Exposure to the NCIS franchise was associated with decreased
intentions to refuse unwanted sexual activity. These results indicate that
exposure to the specific content of each crime drama franchise may have
differential results on sexual consent negotiation behaviors.
PMID- 26418171
TI - What is the potential for context aware communication aids?
AB - Use of voice output communication aids (VOCAs) can be a very effective strategy
to assist people with speech impairments in communicating. Despite this, people
who use communication aids often express frustration with VOCAs-desiring devices
that are simpler, quicker and more effective to use. Whilst it is not possible to
resolve all these issues with technology, it is argued that significant progress
can be made. The use of contextual information is one development that could
improve the simplicity and effectiveness of communication aid design. Improving
the effectiveness of communication aids, including through the use of context
support, is a goal of the NIHR Devices for Dignity Assistive Technology Theme.
This discussion paper examines the potential for creating 'context aware'
communication aids. Three projects in which the authors have been involved are
described to illustrate different approaches to the use of contextual
information.
PMID- 26418172
TI - Genotyping of Toxoplasma gondii Directly from Human and Animal Biological
Samples: From Partial Genotypes to a New Genotype.
AB - Genotyping of Toxoplasma gondii is traditionally performed using DNA obtained
from tachyzoites after isolation by bioassay in mice. In this study, genotyping
of T. gondii was performed by multiplex nested polymerase chain reaction
restriction fragment length polymorphism (Mn-PCR-RFLP) in DNA obtained from the
lungs of experimentally infected mice, the hearts of naturally infected free
range chickens, and human blood samples of newborns with congenital
toxoplasmosis. The efficiency of Mn-PCR varied according to the marker. We
obtained complete genotypes of all of the mice lung samples. In chickens, total
or partial genotyping was performed on all of the 15 samples. Two complete
genotypes were obtained, including one identified for the first time, and another
previously described in different hosts including dogs, cats, and humans. In
blood from infants, partial genotypes were obtained in 8 of the 12 samples. Mouse
bioassay is the most efficient method to obtain DNA from T. gondii , but direct
tissue genotyping enhances the likelihood of obtaining molecular information on
T. gondii and is an effective tool as a complement to isolation in mice. In this
study, we genotyped Toxoplasma gondii directly from human (blood samples of
newborns with congenital toxoplasmosis) and free-range chickens (hearts) by Mn
PCR-RFLP. We present partial and complete genotypes and provide technical and
scientific information about T. gondii genotyping methods.
PMID- 26418173
TI - Cognitive deficits and posttraumatic stress disorder in children: A diagnostic
dilemma illustrated through a case study.
AB - Studies investigating the neuropsychological functioning of children who
experience trauma have predominantly focused on maltreated populations. This
article presents a case study that details the longitudinal outcome of a girl who
experienced a motor vehicle accident at 5 years of age. It highlights the
clinical relevance of research investigating the neuropsychological impact of
single-incident trauma on children. It illustrates difficulties clinicians face
in discriminating between the effects of developmental delay, traumatic brain
injury, attention-deficit/hyperactivity disorder, trauma, and posttraumatic
stress symptoms or posttraumatic stress disorder, especially in children with
compensable injuries. The state of the current literature is discussed, and
directions for future research are provided.
PMID- 26418174
TI - Structural and kinetic investigation of the hydride composite Ca(BH4)2 + MgH2
system doped with NbF5 for solid-state hydrogen storage.
AB - Designing safe, compact and high capacity hydrogen storage systems is the key
step towards introducing a pollutant free hydrogen technology into a broad field
of applications. Due to the chemical bonds of hydrogen-metal atoms, metal
hydrides provide high energy density in safe hydrogen storage media. Reactive
hydride composites (RHCs) are a promising class of high capacity solid state
hydrogen storage systems. Ca(BH4)2 + MgH2 with a hydrogen content of 8.4 wt% is
one of the most promising members of the RHCs. However, its relatively high
desorption temperature of ~350 degrees C is a major drawback to meeting the
requirements for practical application. In this work, by using NbF5 as an
additive, the dehydrogenation temperature of this RHC was significantly
decreased. To elucidate the role of NbF5 in enhancing the desorption properties
of the Ca(BH4)2 + MgH2 (Ca-RHC), a comprehensive investigation was carried out
via manometric measurements, mass spectrometry, Differential Scanning Calorimetry
(DSC), in situ Synchrotron Radiation-Powder X-ray Diffraction (SR-PXD), X-ray
Absorption Spectroscopy (XAS), Anomalous Small-Angle X-ray Scattering (ASAXS),
Scanning and Transmission Electron Microscopy (SEM, TEM) and Nuclear Magnetic
Resonance (NMR) techniques.
PMID- 26418175
TI - Qualitative Exploration of Sexual Experiences Among Adults on the Autism
Spectrum: Implications for Sex Education.
AB - CONTEXT: The increasing prevalence of autism since the 1990s has led to growing
demand for sex education that meets the needs of persons on the autism spectrum.
Yet there is a dearth of research documenting the firsthand experiences and
perspectives of autistic individuals. METHODS: A thematic analysis was conducted
of in-depth, Internet-facilitated interviews with 24 adults on the autism
spectrum who were recruited from Internet community spaces between November 2012
and May 2013. Inclusion criteria were self-identification as a person on the
autism spectrum, being a U.S. resident, being aged 18 or older, and having the
ability to communicate orally or through writing. RESULTS: Participants were aged
18-61 and were living in the community at the time of interview, most with
limited extrafamilial support. They were less likely than the general population
to be heterosexual or gender-conforming and were more likely to have experienced
romantic or sexual debut after age 18. Participants' most common concerns were
courtship difficulties and sensory dysregulation in the context of partnered
sexuality. These concerns were exacerbated by inadequate and inappropriate sex
education experiences. Participants addressed challenges by using sensory
barriers (e.g., latex gloves); planning when and how to have sex; negotiating
alternatives to sexual scripts predicated on nondisabled experience; and
practicing explicit and intentional communication. CONCLUSIONS: Individuals on
the autism spectrum would benefit from sex education that normalizes differences
(e.g., in identities and experiences of sexuality), is offered throughout young
adulthood, addresses disability-relevant sensory and communication needs, and
includes practicing neurotypical sociosexual norms.
PMID- 26418176
TI - Sequence Adaptive Peptide-Polysaccharide Nanostructures by Biocatalytic Self
Assembly.
AB - Coassembly of peptides and polysaccharides can give rise to the formation of
nanostructures with tunable morphologies. We show that in situ enzymatic exchange
of a dipeptide sequence in aromatic peptide amphiphiles/polysaccharide
coassemblies enables dynamic formation and degradation of different
nanostructures depending on the nature of the polysaccharide present. This is
achieved in a one-pot system composed of Fmoc-cysteic acid (CA) and Fmoc-lysine
(K) plus phenylalanine amide (F) in the presence of thermolysin that, through
dynamic hydrolysis and amide formation, gives rise to a dynamic peptide library
composed of the corresponding Fmoc-dipeptides (CAF and KF). When the cationic
polysaccharide chitosan is added to this mixture, selective amplification of the
CAF peptide is observed giving rise to formation of nanosheets through
coassembly. By contrast, upon addition of anionic heparin, KF is formed that
gives rise to a nanotube morphology. The dynamic adaptive potential was
demonstrated by sequential morphology changes depending on the sequence of
polysaccharide addition. This first demonstration of the ability to access
different peptide sequences and nanostructures, depending on the presence of
biopolymers, may pave the way to biomaterials that can adapt their structure and
function and may be of relevance in the design of materials able to undergo
dynamic morphogenesis.
PMID- 26418180
TI - Enantioselective palladium-catalyzed C-H functionalization of indoles using an
axially chiral 2,2'-bipyridine ligand.
AB - A palladium-catalyzed enantioselective C?H functionalization of indoles was
achieved with an axially chiral 2,2'-bipyridine ligand, thus providing the
desired indol-3-acetate derivatives with up to 98 % ee. Moreover, the reaction
protocol was also effective for asymmetric O?H insertion reaction of phenols
using alpha-aryl-alpha-diazoacetates. This represents the first successful
application of bipyridine ligands with axial chirality in palladium-catalyzed
carbene migratory insertion reactions.
PMID- 26418177
TI - PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum
sensing.
AB - Group A Streptococcus (GAS, Streptococcus pyogenes) is a human-restricted
pathogen with a capacity to both colonize asymptomatically and cause illnesses
ranging from pharyngitis to necrotizing fasciitis. An understanding of how and
when GAS switches between genetic programs governing these different lifestyles
has remained an enduring mystery and likely requires carefully tuned
environmental sensors to activate and silence genetic schemes when appropriate.
Herein, we describe the relationship between the Control of Virulence (CovRS,
CsrRS) two-component system and the Rgg2/3 quorum-sensing pathway. We demonstrate
that responses of CovRS to the stress signals Mg(2+) and a fragment of the
antimicrobial peptide LL-37 result in modulated activity of pheromone signaling
of the Rgg2/3 pathway through a means of proteolysis of SHP peptide pheromones.
This degradation is mediated by the cytoplasmic endopeptidase PepO, which is the
first identified enzymatic silencer of an RRNPP-type quorum-sensing pathway.
These results suggest that under conditions in which the virulence potential of
GAS is elevated (i.e. enhanced virulence gene expression), cellular responses
mediated by the Rgg2/3 pathway are abrogated and allow individuals to escape from
group behavior. These results also indicate that Rgg2/3 signaling is instead
functional during non-virulent GAS lifestyles.
PMID- 26418182
TI - Synthesis of bridged diketopiperazines by using the persistent radical effect and
a formal synthesis of bicyclomycin.
AB - A conceptually new and unified approach to diverse bridged diketopiperazines
(DKPs) with widely variable ring sizes was developed by taking advantage of the
persistent radical effect. This method enables synthesis of the core structures
of bridged DKP alkaloids and was applied to a formal synthesis of the antibiotic
bicyclomycin.
PMID- 26418183
TI - B(C6F5)3 -catalyzed transfer of dihydrogen from one unsaturated hydrocarbon to
another.
AB - A transition-metal-free transfer hydrogenation of 1,1-disubstituted alkenes with
cyclohexa-1,4-dienes as the formal source of dihydrogen is reported. The process
is initiated by B(C6 F5 )3 -mediated hydride abstraction from the dihydrogen
surrogate, forming a Bronsted acidic Wheland complex and [HB(C6 F5 )3 ](-) . A
sequence of proton and hydride transfers onto the alkene substrate then yields
the alkane. Although several carbenium ion intermediates are involved, competing
reaction channels, such as dihydrogen release and cationic dimerization of
reactants, are largely suppressed by the use of a cyclohexa-1,4-diene with methyl
groups at the C1 and C5 as well as at the C3 position, the site of hydride
abstraction. The alkene concentration is another crucial factor. The various
reaction pathways were computationally analyzed, leading to a mechanistic picture
that is in full agreement with the experimental observations.
PMID- 26418181
TI - Optogenetic apoptosis: light-triggered cell death.
AB - An optogenetic Bax has been designed that facilitates light-induced apoptosis. We
demonstrate that mitochondrial recruitment of a genetically encoded light
responsive Bax results in the release of mitochondrial proteins, downstream
caspase-3 cleavage, changes in cellular morphology, and ultimately cell death.
Mutagenesis of a key phosphorylatable residue or modification of the C-terminus
mitigates background (dark) levels of apoptosis that result from Bax
overexpression. The mechanism of optogenetic Bax-mediated apoptosis was explored
using a series of small molecules known to interfere with various steps in
programmed cell death. Optogenetic Bax appears to form a mitochondrial apoptosis
induced channel analogous to that of endogenous Bax.
PMID- 26418185
TI - Suicide by Shotgun in Southeastern Minnesota.
AB - Suicide by shotgun is a common method of suicide with high regional variation. We
sought to describe their distinct, challenging features and provide demographic
and risk characteristics. We reviewed 228 gunshot wounds autopsied at Mayo Clinic
from 1994 to 2014; of these, 75 (32.9%) were shotgun wounds. All were suicides
and contact range. Ages ranged from 14 to 92 years old; of these, 97% were men.
The majority involved the head (70.9%), were intraoral (48.2%), and had upward
(73.2%) and backward (73.2%) directionality. Next most common was the chest
(21.5%), with backward (94.1%) and downward (64.7%) directionality. Four involved
multiple wounds. Wadding was recovered in 16 (21.3%) cases. Six (8.0%) had a
survival period. Most (66.7%) took place at home. Seventy-one percent had a known
psychiatric history; 32.4% had positive toxicology. Although contact range
shotgun wounds cause severe destruction, entrance wound and other characteristic
are identifiable with thorough scene, autopsy, and radiographic documentation.
PMID- 26418187
TI - Bismuth Based Hybrid Perovskites A3Bi2 I9 (A: Methylammonium or Cesium) for Solar
Cell Application.
AB - Low-toxic bismuth-based perovskites are prepared for the possible replacement of
lead perovskite in solar cells. The perovskites have a hexagonal crystalline
phase and light absorption in the visible region. A power conversion efficiency
of over 1% is obtained for a solar cell with Cs3 Bi2 I9 perovskite, and it is
concluded that bismuth perovskites have very promising properties for further
development in solar cells.
PMID- 26418188
TI - Missing data in clinical trials for weight management.
AB - In 2014, the US FDA approved liraglutide for weight management. The statistical
review of the application presented various challenges related to the handling of
missing data. The ability of the drug to cause weight loss was not in question.
The challenge centered on obtaining a reliable estimate of the intention-to-treat
effect to support the risk-benefit evaluation. Subjects in the trials that
stopped treatment prior to the endpoint were encouraged to attend the primary
endpoint visit. Data from the subjects that returned for a primary efficacy
assessment played a significant role in the statistical review. They were used to
illustrate shortcomings of the applicant's primary efficacy analysis and
sensitivity analyses. They were also used in the FDA analyses to address missing
data. The goal of this article is to illustrate challenges and considerations
associated with the handling of missing data in clinical trials.
PMID- 26418186
TI - Function and control of human invasive trophoblast subtypes: Intrinsic vs.
maternal control.
AB - The establishment of a functional placenta is pivotal for normal fetal
development and the maintenance of pregnancy. In the course of early
placentation, trophoblast precursors differentiate into highly invasive
trophoblast subtypes. These cells, referred to as extravillous trophoblasts
(EVTs), penetrate the maternal uterus reaching as far as the inner third of the
myometrium. One of the most fundamental functions of EVTs is the transformation
of spiral arteries to establish the uteroplacental blood circulation assuring an
adequate nutrient and gas supply to the developing fetus. To achieve this,
specialized EVT subpopulations interact with maternal immune cells, provoke
elastolysis in the arterial wall and replace the endothelial cells lining the
spiral arteries to induce intraluminal vascular remodeling. These and other
trophoblast-mediated processes are tightly controlled by paracrine signals from
the maternal decidua and furthermore underlie an intrinsic cell-type specific
program. Various severe pregnancy complications such as preeclampsia or
intrauterine growth retardation are associated with abnormal EVT function,
shallow invasion, and decreased blood flow to the placenta. Hence a better
understanding of human trophoblast invasion seems mandatory to improve
therapeutic intervention. This approach, however, requires a profound knowledge
of the human placenta, its various trophoblast subtypes and in particular a
better understanding of the regulatory network that controls the invasive
phenotype of EVTs.
PMID- 26418189
TI - Additional sampling directions improve detection range of wireless radiofrequency
probes.
AB - PURPOSE: While MRI is enhancing our knowledge about the structure and function of
the human brain, subject motion remains a problem in many clinical applications.
Recently, the use of wireless radiofrequency markers with three one-dimensional
(1D) navigators for prospective correction was demonstrated. This method is
restricted in the range of motion that can be corrected, however, because of
limited information in the 1D readouts. METHODS: Here, the limitation of
techniques for disambiguating marker locations was investigated. It was shown
that including more sampling directions extends the tracking range for head
rotations. The efficiency of trading readout resolution for speed was explored.
RESULTS: Tracking of head rotations was demonstrated from -19.2 to 34.4 degrees ,
-2.7 to 10.0 degrees , and -60.9 to 70.9 degrees in the x-, y-, and z
directions, respectively. In the presence of excessive head motion, the deviation
of marker estimates from SPM8 was reduced by 17.1% over existing three-projection
methods. This was achieved by using an additional seven directions, extending the
time needed for readouts by a factor of 3.3. Much of this increase may be
circumvented by reducing resolution, without compromising accuracy. CONCLUSION:
Including additional sampling directions extends the range in which markers can
be used, for patients who move a lot. Magn Reson Med 76:913-918, 2016. (c) 2015
The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc.
on behalf of International Society for Magnetic Resonance in Medicine. This is an
open access article under the terms of the Creative Commons Attribution License,
which permits use, distribution and reproduction in any medium, provided the
original work is properly cited.
PMID- 26418190
TI - Free Energy Calculations using a Swarm-Enhanced Sampling Molecular Dynamics
Approach.
AB - Free energy simulations are an established computational tool in modelling
chemical change in the condensed phase. However, sampling of kinetically distinct
substates remains a challenge to these approaches. As a route to addressing this,
we link the methods of thermodynamic integration (TI) and swarm-enhanced sampling
molecular dynamics (sesMD), where simulation replicas interact cooperatively to
aid transitions over energy barriers. We illustrate the approach by using
alchemical alkane transformations in solution, comparing them with the multiple
independent trajectory TI (IT-TI) method. Free energy changes for transitions
computed by using IT-TI grew increasingly inaccurate as the intramolecular
barrier was heightened. By contrast, swarm-enhanced sampling TI (sesTI)
calculations showed clear improvements in sampling efficiency, leading to more
accurate computed free energy differences, even in the case of the highest
barrier height. The sesTI approach, therefore, has potential in addressing
chemical change in systems where conformations exist in slow exchange.
PMID- 26418192
TI - Missed stroke in acute vertigo and dizziness: It is time for action, not debate.
PMID- 26418193
TI - Corrigendum.
PMID- 26418191
TI - Safety of guidewire-based measurement of fractional flow reserve and the index of
microvascular resistance using intravenous adenosine in patients with acute or
recent myocardial infarction.
AB - AIMS: Coronary guidewire-based diagnostic assessments with hyperemia may cause
iatrogenic complications. We assessed the safety of guidewire-based measurement
of coronary physiology, using intravenous adenosine, in patients with an acute
coronary syndrome. METHODS: We prospectively enrolled invasively managed STEMI
and NSTEMI patients in two simultaneously conducted studies in 6 centers
(NCT01764334; NCT02072850). All of the participants underwent a diagnostic
coronary guidewire study using intravenous adenosine (140 MUg/kg/min) infusion
for 1-2 min. The patients were prospectively assessed for the occurrence of
serious adverse events (SAEs) and symptoms and invasively measured hemodynamics
were also recorded. RESULTS: 648 patients (n=298 STEMI patients in 1 hospital;
mean time to reperfusion 253 min; n=350 NSTEMI in 6 hospitals; median time to
angiography from index chest pain episode 3 (2, 5) days) were included between
March 2011 and May 2013. Two NSTEMI patients (0.3% overall) experienced a
coronary dissection related to the guidewire. No guidewire dissections occurred
in the STEMI patients. Chest symptoms were reported in the majority (86%) of
patient's symptoms during the adenosine infusion. No serious adverse events
occurred during infusion of adenosine and all of the symptoms resolved after the
infusion ceased. CONCLUSIONS: In this multicenter analysis, guidewire-based
measurement of FFR and IMR using intravenous adenosine was safe in patients
following STEMI or NSTEMI. Self-limiting symptoms were common but not associated
with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI
patients was noted to be a rare phenomenon.
PMID- 26418194
TI - Wet Nanoindentation of the Solid Electrolyte Interphase on Thin Film Si
Electrodes.
AB - The solid electrolyte interphase (SEI) film formed at the surface of negative
electrodes strongly affects the performance of a Li-ion battery. The mechanical
properties of the SEI are of special importance for Si electrodes due to the
large volumetric changes of Si upon (de)insertion of Li ions. This manuscript
reports the careful determination of the Young's modulus of the SEI formed on a
sputtered Si electrode using wet atomic force microscopy (AFM)-nanoindentation.
Several key parameters in the determination of the Young's modulus are considered
and discussed, e.g., wetness and roughness-thickness ratio of the film and the
shape of a nanoindenter. The values of the Young's modulus were determined to be
0.5-10 MPa under the investigated conditions which are in the lower range of
those previously reported, i.e., 1 MPa to 10 GPa, pointing out the importance of
the conditions of its determination. After multiple electrochemical cycles, the
polymeric deposits formed on the surface of the SEI are revealed, by force-volume
mapping in liquid using colloidal probes, to extend up to 300 nm into bulk
solution.
PMID- 26418196
TI - Improvement of J(sc) in a Cu2ZnSnS4 Solar Cell by Using a Thin Carbon
Intermediate Layer at the Cu2ZnSnS4/Mo Interface.
AB - Back contact modification plays an important role in improving energy conversion
efficiency of Cu2ZnSnS4 (CZTS) thin film solar cells. In this paper, an ultrathin
carbon layer is introduced on molybdenum (Mo)-coated soda lime glass (SLG) prior
to the deposition of CZTS precursor to improve the back contact and therefore
enhance CZTS solar cell efficiency. By introducing this layer, the short circuit
current (Jsc) and device conversion efficiency increase for both nonvacuum (sol
gel) and vacuum (sputtering) methods. Specifically, for the sol-gel based
process, Jsc increases from 13.60 to 16.96 mA/cm(2) and efficiency from 4.47% to
5.52%, while for the sputtering based process, Jsc increases from 17.50 to 20.50
mA/cm(2) and efficiency from 4.10% to 5.20%. Furthermore, introduction of this
layer does not lead to any deterioration of either open circuit voltage (Voc) or
fill factor (FF).
PMID- 26418195
TI - Glyconanomaterials for Combating Bacterial Infections.
AB - Bacterial infections constitute an increasing problem to human health in response
to build-up of resistance to present antibiotics and sluggish development of new
pharmaceuticals. However, a means to address this problem is to pinpoint the drug
delivery to-and into-the bacteria. This results in a high local concentration of
the drug, circumventing the increasingly high doses otherwise necessary. Combined
with other effectors, such as covalent attachment to carriers, rendering the
drugs less degradable, and the combination with efflux inhibitors, old drugs can
be revived. In this context, glyconanomaterials offer exceptional potential,
since these materials can be tailored to accommodate different effectors. In this
Concept article, we describe the different advantages of glyconanomaterials, and
point to their potential in antibiotic "revitalization".
PMID- 26418199
TI - Correction.
PMID- 26418197
TI - Another Frontier in Microbiome Research: Preterm Birth.
PMID- 26418200
TI - Correction.
PMID- 26418202
TI - Systematic Review of Outcomes After Noncardiac Surgery in Patients with Implanted
Left Ventricular Assist Devices.
AB - The number of patients supported with left ventricular assist devices (LVADs) is
rising rapidly, and noncardiac surgery (NCS) in these patients presents unique
challenges. Given the controversy regarding the safety and timing of elective
NCS, we performed a systematic review examining the perioperative morbidity and
mortality of NCS in stable patients with LVADs. The published literature was
searched using strategies created by a medical librarian. All reports involving
five or more patients with implanted LVAD undergoing NCS were eligible for
inclusion. One hundred and sixty one patients who underwent 252 surgeries were
included from seven studies. Cohort size ranged from 8 to 47 patients undergoing
12 to 67 NCS. Median age ranged from 50.1 to 68 years and 75 to 100% were male.
Thirty day postoperative mortality ranged from 6.4 to 16.7%, although four
studies reported no deaths. Due to the small number of included studies with
relative few patients and widely heterogeneous reporting of outcomes a formal
quantitative meta-analysis was not performed. Noncardiac surgery in patients with
LVADs appears to be safe and feasible in select patients. Future studies should
use standard study design and reporting parameters to facilitate the systematic
examination of safety and outcomes for elective NCS in LVAD patients.
PMID- 26418201
TI - Generation of Two Biological Wound Dressings as a Potential Delivery System of
Human Adipose-Derived Mesenchymal Stem Cells.
AB - Human adipose-derived mesenchymal stem cells (hADMSCs) are believed to be
potential key factors for starting the regenerative process after tissue injury.
However, an efficient method of delivering these regenerative cells to an
external wound site is still lacking. Human amnion and pig skin have long been
used as skin wound dressings for the treatment of burns and other skin lesions.
Herein, we present the generation of two constructs using these two biomaterials
as effective scaffolds for the culture of hADMSCs. It was found that hADMSCs
seeded onto radiosterilized human amnion and pig skin are viable and proliferate.
These cells are able to migrate over these scaffolds as demonstrated by using
time-lapse microscopy. In addition, the scaffolds induce hADMSCs to secrete
interleukin-10, an important negative regulator of inflammation, and interleukin
1beta, a proinflammatory protein. The interplay between these two proteins has
been proven to be vital for a balanced restoration of all necessary tissues.
Thus, radiosterilized human amnion and pig skin are likely suitable scaffolds for
delivery of hADMSCs transplants that could promote tissue regeneration in skin
injuries like patients with burn injuries.
PMID- 26418203
TI - Convective Leakage Makes Heparin Locking of Central Venous Catheters Ineffective
Within Seconds: Experimental Measurements in a Model Superior Vena Cava.
AB - Central venous catheters (CVCs), placed in the superior vena cava (SVC) for
hemodialysis or chemotherapy, are routinely filled while not in use with heparin,
an anticoagulant, to maintain patency and prevent thrombus formation at the
catheter tip. The heparin-locking procedure, however, places the patient at risk
for systemic bleeding, as heparin is known to leak from the catheter into the
blood stream. We provide evidence from detailed in vitro experiments that shows
the driving mechanism behind heparin leakage to be convective-diffusive transport
due to the pulsatile flow surrounding the catheter. This novel mechanism is
supported by experimental planar laser-induced fluorescence (PLIF) and particle
image velocimetry (PIV) measurements of flow velocity and heparin transport from
a CVC placed inside a model SVC inside a pulsatile flow loop. The results predict
an initial, fast (<10 s), convection-dominated phase that rapidly depletes the
concentration of heparin in the near-tip region, the region of the catheter with
side holes. This is followed by a slow, diffusion-limited phase inside the
catheter lumen, where the concentration is still high, that is insufficient at
replenishing the lost heparin concentration in the near-tip region. The results
presented here, which are consistent with previous in vivo estimates of 24 hour
leakage rates, predict that the concentration of heparin in the near-tip region
is essentially zero for the majority of the interdialytic phase, rendering the
heparin locking procedure ineffective.
PMID- 26418204
TI - Predictors of Thromboembolic Events in Patients with Ventricular Assist Device.
AB - Ventricular assist device patients (VAD) are at increased risk for
thromboembolism. Biomarkers of hemolysis, such as lactate dehydrogenase (LDH) and
poorly controlled international normalized ratio (INR) has been identified as
predictors of thromboembolism. Patients aged 19 years and older who had a
continuous flow VAD placed from 2006 to 2012 were included in this study (N =
115). We assessed the relationship of LDH elevation (>=600 IU/L) at different
time points and thromboembolism. Over the 51.3 person-years of follow-up, a total
of 23 first thromboembolic events occurred. Patients with elevated LDH on the day
of VAD implantation had an increased risk for thromboembolism (hazard ratio [HR]:
4.72, 95% confidence interval [CI]: 1.44-15.4; p = 0.01). There was an increased
risk of thromboembolism with early LDH elevation within the first month post-VAD
(HR: 4.95, 95% CI: 1.69-14.4; p = 0.003) and estimated glomerular filtration rate
<30 before VAD implantation (HR: 4.74, 95% CI: 1.12-20.1; p = 0.0346), whereas
there was a decreased risk with good anticoagulation control (HR: 0.30, 95% CI:
0.10-0.86; p = 0.0247). Our study is the first to highlight the association
between LDH elevation on the day of implantation and post-VAD thromboembolism.
This study details the increased risk of thromboembolism with early LDH elevation
and the importance of maintaining time in therapeutic INR range.
PMID- 26418205
TI - Effects of Sevoflurane Inhalation During Cardiopulmonary Bypass on Pediatric
Patients: A Randomized Controlled Clinical Trial.
AB - The effects of sevoflurane inhalation during cardiopulmonary bypass (CPB) on
postoperative courses and serum cardiac troponin I (cTnI) concentrations in
pediatric patients undergoing cardiac surgery have not been extensively
investigated. In this single-center, prospective, randomized trial, an anesthetic
regimen containing 2% sevoflurane used throughout the CPB process was compared
with a total intravenous anesthesia (TIVA) regimen. One hundred and three
patients undergoing congenital heart defect repair with CPB were included in this
prospective randomized controlled study. They were randomized into two groups:
the sevoflurane group, who received 2% sevoflurane during CPB via an oxygenator,
and the control group, who received only an oxygen-air mixture. The pre- and
intra-operative parameters were comparable between the two groups. There was a
slight but significant increase of arterial diastolic pressure in the sevoflurane
group immediately after CPB compared with control patients (46.9 +/- 9.3 mm Hg
vs. 43.6 +/- 8.9 mm Hg; p = 0.033). There was no death in either group. The
postoperative ventilation time (in mean [95% confidence interval]) was shorter in
the sevoflurane group than that in the control group (26.1 [19.2, 33.0] h vs.
37.7 [24.4, 50.9] h; p = 0.014). The postoperative ICU time, hospital days, and
serial serum cTnI concentrations were not significantly different between the two
groups. Inhalation of 2% sevoflurane during CPB is beneficial to the recovery of
pediatric patients undergoing cardiac surgery but has no significant effect on
postoperative cTnI release.
PMID- 26418206
TI - Safety Management of a Clinical Process Using Failure Mode and Effect Analysis:
Continuous Renal Replacement Therapies in Intensive Care Unit Patients.
AB - The failure mode and effect analysis (FMEA) may improve the safety of the
continuous renal replacement therapies (CRRT) in the intensive care unit. We use
this tool in three phases: 1) Retrospective observational study. 2) A process
FMEA, with implementation of the improvement measures identified. 3) Cohort study
after FMEA. We included 54 patients in the pre-FMEA group and 72 patients in the
post-FMEA group. Comparing the risks frequencies per patient in both groups, we
got less cases of under 24 hours of filter survival time in the post-FMEA group
(31 patients 57.4% vs. 21 patients 29.6%; p < 0.05); less patients suffered
circuit coagulation with inability to return the blood to the patient (25
patients [46.3%] vs. 16 patients [22.2%]; p < 0.05); 54 patients (100%) versus 5
(6.94%) did not get phosphorus levels monitoring (p < 0.05); in 14 patients
(25.9%) versus 0 (0%), the CRRT prescription did not appear on medical orders. As
a measure of improvement, we adopt a dynamic dosage management. After the process
FMEA, there were several improvements in the management of intensive care unit
patients receiving CRRT, and we consider it a useful tool for improving the
safety of critically ill patients.
PMID- 26418207
TI - Renal Function Recovery with Total Artificial Heart Support.
AB - Heart failure patients requiring total artificial heart (TAH) support often have
concomitant renal insufficiency (RI). We sought to quantify renal function
recovery in patients supported with TAH at our institution. Renal function data
at 30, 90, and 180 days after TAH implantation were analyzed for patients with
RI, defined as hemodialysis supported or an estimated glomerular filtration rate
(eGFR) less than 60 ml/min/1.73 m. Between January 2008 and December 2013, 20 of
the 46 (43.5%) TAH recipients (age 51 +/- 9 years, 85% men) had RI, mean
preoperative eGFR of 48 +/- 7 ml/min/1.73 m. Renal function recovery was noted at
each follow-up interval: increment in eGFR (ml/min/1.73 m) at 30, 90, and 180
days was 21 +/- 35 (p = 0.1), 16.5 +/- 18 (p = 0.05), and 10 +/- 9 (p = 0.1),
respectively. Six patients (30%) required preoperative dialysis. Of these, four
recovered renal function, one remained on dialysis, and one died. Six patients
(30%) required new-onset dialysis. Of these, three recovered renal function and
three died. Overall, 75% (15 of 20) of patients' renal function improved with TAH
support. Total artificial heart support improved renal function in 75% of
patients with pre-existing significant RI, including those who required
preoperative dialysis.
PMID- 26418208
TI - Incidence of Hemolysis in Patients with Cardiogenic Shock Treated with Impella
Percutaneous Left Ventricular Assist Device.
AB - Impella assist devices have been increasingly used in cardiogenic shock (CS).
This study aims to assess the incidence of hemolysis when Impella support is used
longer than 6 hours in CS. We retrospectively studied all patients who required
Impella between April 2009 and September 2013. Demographic data and hemolysis
indicators were sampled and analyzed using paired t-test. A total of 118 devices
were placed and 40 used longer than 6 hours. The average time of support was
86.63 hours, and the 30 and 90 days of survival were 65% and 60%, respectively.
After 24 hours of support, the hemoglobin (Hb) decreased significantly despite
17% of patients receiving blood transfusion (p = 0.0001). By the time of removal,
65% of patients were transfused to maintain a Hb of 10 mg/dl (p = 0.0014). The
lactate dehydrogenase (LDH) increased to 5,201 U/L (n = 22; p = 0.0096), the
bilirubin to 5.6 mg/dl (p = 0.008), and the haptoglobin level was 15.4 mg/dl (n =
25). The cumulative incidence of hemolysis was 62.5%. Hemolysis is a common
occurrence in patients with long-term Impella support for CS, evaluated by the
persistent decline in Hb and haptoglobin as well as increase in LDH and
bilirubin. Strict monitoring of hemolysis parameters at baseline and at frequent
intervals is crucial.
PMID- 26418209
TI - Distal Proctocolitis in Infants: Is It Always an Allergic Disease?
PMID- 26418210
TI - Attrition in Long-Term Nutrition Research Studies: A Commentary by the European
Society for Pediatric Gastroenterology, Hepatology, and Nutrition Early Nutrition
Research Working Group.
AB - Long-term follow-up of randomised trials and observational studies provide the
best evidence presently available to assess long-term effects of nutrition, and
such studies are an important component in determining optimal infant feeding
practices. Attrition is, however, an almost inevitable occurrence with increasing
age at follow-up. There is a common assumption that studies with <80% follow-up
rates are invalid or flawed, and this criticism seems to be more frequently
applied to follow-up studies involving randomised trials than observational
studies. In this article, we explore the basis and evidence for this "80% rule"
and discuss the need for greater consensus and clear guidelines for analysing and
reporting results in this specific situation.
PMID- 26418211
TI - One Extra Gram of Protein to Preterm Infants From Birth to 1800 g: A Single
Blinded Randomized Clinical Trial.
AB - OBJECTIVE: The aim of the study was to evaluate the effect on growth and
neurodevelopment of increasing amino acid (AA) during parenteral nutrition and
protein intake during enteral nutrition in extremely low birth-weight infants
starting from birth to day of reaching 1800 g body weight. METHODS: We randomized
preterm infants with birth weight 500 to 1249 g either to a high AA/protein
intake (HiP [high protein]: parenteral nutrition = 3.5 AA, enteral nutrition =
4.6 protein g . kg . day) or to a standard of care group (StP [standard protein]:
parenteral nutrition = 2.5 AA, enteral nutrition = 3.6 protein g . kg . day). The
primary outcome was weight gain from birth to 1800 g. RESULTS: TWO:: hundred
twenty-six patients were screened, 164 completed the study and were analyzed (82
StP and 82 HiP). Cumulative AA/protein intake from birth to 1800 g was 178 +/- 42
versus 223 +/- 45 g/kg in the StP versus HiP group respectively, P < 0.0001.Blood
urea was higher in HiP than in StP group both during parenteral and enteral
nutrition (P = 0.004).Weight gain from birth to 1800 g was 12.3 +/- 1.6 in StP
and 12.6 +/- 1.7 g . kg . day in HiP group (P = 0.294). We found no difference in
any growth parameters neither during hospital stay nor at 2 years corrected age.
Bayley III score at 24 months corrected age was 93.8 +/- 12.9 in StP group and
94.0 +/- 13.9 in the HiP group, P = 0.92. CONCLUSIONS: Increasing AA/protein
intake both during parenteral and enteral nutrition does not improve growth and
neurodevelopment of small preterm infants 500 to 1249 g birth weight.
PMID- 26418212
TI - Identification and Management of Acute Malnutrition in Hospitalized Children:
Developed Country Perspective.
PMID- 26418213
TI - Pancreatitis Subtypes Survey in 852 Childhood-Onset Systemic Lupus Erythematosus
Patients.
AB - OBJECTIVE: Pancreatitis is a rare and a life-threatening systemic lupus
erythematosus (SLE) manifestation in childhood-onset SLE (cSLE). The objective of
this study was to systematically classify pancreatitis in cSLE according to the
International Study Group of Pediatric Pancreatitis and determine the overall
prevalence, clinical features, laboratory, and first episode outcomes. METHODS: A
multicenter cohort study in 10 pediatric rheumatology centers, including 852
patients with cSLE. RESULTS: Pancreatitis was diagnosed in 22 of 852 (2.6%)
patients with cSLE. It was classified as acute pancreatitis in 20 (91%), acute
recurrent pancreatitis in 2 (9%), and none of them had chronic pancreatitis. None
of them had gallstones, traumatic pancreatitis, or reported alcohol/tobacco use.
The comparison of patients with pancreatitis (first episode) and without this
complication revealed a shorter disease duration (1 [0-10] vs 4 [0-23] years, P <
0.0001) and higher median of Systemic Lupus Erythematosus Disease Activity Index
2000 (21 [0-41] vs 2 [0-45], P < 0.0001). The frequencies of fever (P < 0.0001),
weight loss (P < 0.0001), serositis (P < 0.0001), nephritis (P < 0.0001),
arterial hypertension (P < 0.0001), acute renal failure (P < 0.0001), macrophage
activation syndrome (P < 0.0001), and death (P = 0.001) were also higher in
patients with pancreatitis. The frequencies of intravenous methylprednisolone use
(P < 0.0001) and the median of prednisone dose (55 [15-60] vs 11 [1-90] mg/day, P
< 0.0001) were significantly higher in patients with pancreatitis. Of note, the 2
patients with acute recurrent pancreatitis had 2 episodes, with pain-free
interval of 1 and 4 years. CONCLUSIONS: This was the first study characterizing
pancreatitis using the International Study Group of Pediatric Pancreatitis
standardized definitions in patients with cSLE showing that the predominant form
is acute pancreatitis seen in association with glucocorticoid treatment and
active severe disease.
PMID- 26418214
TI - Liver Transplantation for Biliary Atresia: Is There a Difference in Outcome for
Infants?
AB - OBJECTIVES: Liver transplantation (LT) in children with biliary atresia (BA) is
often performed because of poor bile drainage, complications of biliary
cirrhosis, or recurrent cholangitis. Poor bile drainage after a Kasai
hepatoportoenterostomy is the primary driver for LT in infancy. The aim of the
present study was to compare the clinical characteristics and outcome of first
isolated liver transplantation for infants with BA who underwent transplant
before 2 years of age (transplanted at infancy [TAI]) with children transplanted
later in life (age 2-<18 years = transplanted at childhood [TAC]). METHODS:
Children with BA who underwent LT between 2002 and 2012 were identified from the
United Network for Organ Sharing Standard Transplant Analysis and Research data
set files. RESULTS: A total of 1818 children underwent first isolated liver
transplantation for BA (TAI 1408 [77.4%]; TAC 410 [22.6%]). One and 5-year
patient survival of the TAI and TAC patients was 95.2%, 93.8%, and 97.8 %, 97.1%,
respectively (P < 0.01 for both periods). One and 5-year graft survival of the
TAI and TAC patients was 87.6%, 84.6 % and 93.2%, 90.7%, respectively (P < 0.01
for both periods). Removal from the waitlist for disease progression or death was
significantly higher for TAI compared with TAC (120 patients [6.3%] vs 21 [3.7%],
P = 0.02). Cold ischemic time was found to be the prognostic factor for death
after LT in TAI, whereas being on life support was a poor prognostic factor in
TAC by multivariate risk factor analysis. CONCLUSIONS: The vast majority of
transplants for BA occur in children <2 years of age. Younger patients with BA
had significantly higher waitlist and posttransplant mortality. Given the
consistently poorer outcomes, there is an urgent need to find methods to improve
bile drainage after the Kasai hepatoportoenterostomy.
PMID- 26418216
TI - An analytic linear accelerator source model for GPU-based Monte Carlo dose
calculations.
AB - Recently, there has been a lot of research interest in developing fast Monte
Carlo (MC) dose calculation methods on graphics processing unit (GPU) platforms.
A good linear accelerator (linac) source model is critical for both accuracy and
efficiency considerations. In principle, an analytical source model should be
more preferred for GPU-based MC dose engines than a phase-space file-based model,
in that data loading and CPU-GPU data transfer can be avoided. In this paper, we
presented an analytical field-independent source model specifically developed for
GPU-based MC dose calculations, associated with a GPU-friendly sampling scheme. A
key concept called phase-space-ring (PSR) was proposed. Each PSR contained a
group of particles that were of the same type, close in energy and reside in a
narrow ring on the phase-space plane located just above the upper jaws. The model
parameterized the probability densities of particle location, direction and
energy for each primary photon PSR, scattered photon PSR and electron PSR. Models
of one 2D Gaussian distribution or multiple Gaussian components were employed to
represent the particle direction distributions of these PSRs. A method was
developed to analyze a reference phase-space file and derive corresponding model
parameters. To efficiently use our model in MC dose calculations on GPU, we
proposed a GPU-friendly sampling strategy, which ensured that the particles
sampled and transported simultaneously are of the same type and close in energy
to alleviate GPU thread divergences. To test the accuracy of our model, dose
distributions of a set of open fields in a water phantom were calculated using
our source model and compared to those calculated using the reference phase-space
files. For the high dose gradient regions, the average distance-to-agreement
(DTA) was within 1 mm and the maximum DTA within 2 mm. For relatively low dose
gradient regions, the root-mean-square (RMS) dose difference was within 1.1% and
the maximum dose difference within 1.7%. The maximum relative difference of
output factors was within 0.5%. Over 98.5% passing rate was achieved in 3D gamma
index tests with 2%/2 mm criteria in both an IMRT prostate patient case and a
head-and-neck case. These results demonstrated the efficacy of our model in terms
of accurately representing a reference phase-space file. We have also tested the
efficiency gain of our source model over our previously developed phase-space-let
file source model. The overall efficiency of dose calculation was found to be
improved by ~1.3-2.2 times in water and patient cases using our analytical model.
PMID- 26418215
TI - Caring Decisions: The Development of a Written Resource for Parents Facing End-of
Life Decisions.
AB - BACKGROUND: Written resources in adult intensive care have been shown to benefit
families facing end of life (EoL) decisions. There are few resources for parents
making EoL decisions for their child and no existing resources addressing ethical
issues. The Caring Decisions handbook and website were developed to fill these
gaps. AIM: We discuss the development of the resources, modification after
reviewer feedback and findings from initial pilot implementation. DESIGN: A
targeted literature review-to identify resources and factors that impact on
parental EoL decision-making; development phase-guided by the literature and the
researchers' expertise; consultation process-comprised a multi-disciplinary panel
of experts and parents; pilot evaluation study-hard-copy handbook was distributed
as part of routine care at an Australian Children's Hospital.
SETTING/PARTICIPANTS: Twelve experts and parents formed the consultation panel.
Eight parents of children with life-limiting conditions and clinicians were
interviewed in the pilot study. RESULTS: Numerous factors supporting/impeding EoL
decisions were identified. Caring Decisions addressed issues identified in the
literature and by the multidisciplinary research team. The consultation panel
provided overwhelmingly positive feedback. Pilot study parents found the
resources helpful and comforting. Most clinicians viewed the resources as very
beneficial to parents and identified them as ideal for training purposes.
CONCLUSIONS: The development of the resources addressed many of the gaps in
existing resources. The consultation process and the pilot study suggest these
resources could be of significant benefit to parents and clinicians.
PMID- 26418217
TI - WITHDRAWN: Adenotonsillectomy for obstructive sleep apnoea in children.
PMID- 26418218
TI - Reaction of Laser-Ablated Uranium and Thorium Atoms with H2Se: A Rare Example of
Selenium Multiple Bonding.
AB - The compounds H2ThSe and H2USe were synthesized by the reaction of laser-ablated
actinide metal atoms with H2Se under cryogenic conditions following the
procedures used to synthesize H2AnX (An = Th, U; X = O, S). The molecules were
characterized by infrared spectra in an argon matrix with the aid of deuterium
substitution and electronic structure calculations at the density functional
theory level. The main products, H2ThSe and H2USe, are shown to have a highly
polarized actinide-selenium triple bond, as found for H2AnS on the basis of
electronic structure calculations. There is an even larger back-bonding of the Se
with the An than found for the corresponding sulfur compounds. These molecules
are of special interest as rare examples of multiple bonding of selenium to a
metal, particularly an actinide metal.
PMID- 26418219
TI - Cardioprotective Actions of TGFbetaRI Inhibition Through Stimulating
Autocrine/Paracrine of Survivin and Inhibiting Wnt in Cardiac Progenitors.
AB - Heart failure due to myocardial infarction (MI) is a major cause of morbidity and
mortality in the world. We found previously that A83-01, a TGFbetaRI inhibitor,
could facilitate cardiac repair in post-MI mice and induce the expansion of a
Nkx2.5 + cardiomyoblast population. This study aimed to investigate the key
autocrine/paracrine factors regulated by A83-01 in the injured heart and the
mechanism of cardioprotection by this molecule. Using a previously described
transgenic Nkx2.5 enhancer-green fluorescent protein (GFP) reporter mice, we
isolated cardiac progenitor cells (CPC) including Nkx2.5-GFP + (Nkx2.5+), sca1+,
and Nkx2.5+/sca1 + cells. A83-01 was found to induce proliferation of these three
subpopulations mainly through increasing Birc5 expression in the MEK/ERK
dependent pathway. Survivin, encoded by Birc5, could also directly proliferate
Nkx2.5 + cells and enhance cultured cardiomyocytes viability. A83-01 could also
reverse the downregulation of Birc5 in postinjured mice hearts (n = 6) to expand
CPCs. Moreover, the increased Wnt3a in postinjured hearts could decrease CPCs,
which could be reversed by A83-01 via inhibiting Fzd6 and Wnt1-induced signaling
protein 1 expressions in CPCs. Next, we used inducible alphaMHC-cre/mTmG mice to
label cardiomyocytes with GFP and nonmyocytes with RFP. We found A83-01 preserved
more GFP + myocytes (68.6% +/- 3.1% vs. 80.9% +/- 3.0%; p < .05, n = 6) and fewer
renewed RFP + myocytes (0.026% +/- 0.005% vs. 0.062% +/- 0.008%; p < .05, n = 6)
in parallel with less cardiac fibrosis in isoprenaline-injected mice treated with
A83-01. TGFbetaRI inhibition in an injured adult heart could both stimulate the
autocrine/paracrine activity of survivin and inhibit Wnt in CPCs to mediate
cardioprotection and improve cardiac function.
PMID- 26418220
TI - Urease and Dental Plaque Microbial Profiles in Children.
AB - OBJECTIVE: Urease enzymes produced by oral bacteria generate ammonia, which can
have a significant impact on the oral ecology and, consequently, on oral health.
To evaluate the relationship of urease with dental plaque microbial profiles in
children as it relates to dental caries, and to identify the main contributors to
this activity. METHODS: 82 supragingival plaque samples were collected from 44
children at baseline and one year later, as part of a longitudinal study on
urease and caries in children. DNA was extracted; the V3-V5 region of the 16S
rRNA gene was amplified and sequenced using 454 pyrosequencing. Urease activity
was measured using a spectrophotometric assay. Data were analyzed with Qiime.
RESULTS: Plaque urease activity was significantly associated with the composition
of the microbial communities of the dental plaque (Baseline P = 0.027, One Year P
= 0.012). The bacterial taxa whose proportion in dental plaque exhibited
significant variation by plaque urease levels in both visits were the family
Pasteurellaceae (Baseline P<0.001; One Year P = 0.0148), especially Haemophilus
parainfluenzae. No association was observed between these bacteria and dental
caries. Bacteria in the genus Leptotrichia were negatively associated with urease
and positively associated with dental caries (Bonferroni P<0.001). CONCLUSIONS:
Alkali production by urease enzymes primarily from species in the family
Pasteurellaceae can be an important ecological determinant in children's dental
plaque. Further studies are needed to establish the role of urease-associated
bacteria in the acid/base homeostasis of the dental plaque, and in the
development and prediction of dental caries in children.
PMID- 26418221
TI - Chronic maternal morphine alters calbindin D-28k expression pattern in postnatal
mouse brain.
AB - The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be
altered in several brain regions of chronic morphine exposed adult mice. In this
study, the influence of chronic maternal exposure to morphine on the distribution
pattern of CB-D28k-expressing neurons in the brain of mouse offspring was
investigated. Females of CD-1 mice were daily administered with saline or
morphine for 7 days before mating, during the whole gestation period, and until
21 day post-partum. Their offspring were sacrificed on postnatal day 18, and the
brains were examined by histology using cresyl violet and by immunohistochemistry
using a rabbit polyclonal anti-CB-D28k antibody. Histology revealed no
significant differences in the distribution pattern and the number of neurons
between the offspring forebrain of the control group of mice and the two groups
of mice treated with different doses of morphine. However, immunohistochemical
analysis revealed that the number of CB-D28k-immunoreactive neurons remarkably
decreased in the cingulate cortex, in the layers II-IV of the parietal cortex and
in all regions of the hippocampus, while it increased in the layers V-VI of the
parietal cortex and in the subicular region of the offspring brain of morphine
treated mice. Overall, our findings demonstrate that maternal exposure to
morphine alters the pattern of CB-D28k-expressing neuron pattern in specific
regions of murine developing brain, in a layer- and dose-dependent way, thus
suggesting that these alterations might represent a mechanism by which morphine
modifies the functional aspects of developing brain.
PMID- 26418223
TI - Transcendent Pluralism: A Middle-Range Theory of Nonviolent Social Transformation
Through Human and Ecological Dignity.
AB - Transcendent pluralism is a middle-range theory that focuses on the emergence of
human dignity within relationships among diverse peoples through nonviolent
social transformation. The theory proposes that contemporary social problems that
negatively influence health are rooted in human and ecological devaluation and
that healing is needed through the advance of dignity. The theory has been
developed through both deductive and inductive processes including 4 research
studies. The theory of transcendent pluralism provides a framework for nurses
seeking to advance dignity. This article provides an overview of the theory's
development and components.
PMID- 26418222
TI - High Intensity Exercise in Multiple Sclerosis: Effects on Muscle Contractile
Characteristics and Exercise Capacity, a Randomised Controlled Trial.
AB - INTRODUCTION: Low-to-moderate intensity exercise improves muscle contractile
properties and endurance capacity in multiple sclerosis (MS). The impact of high
intensity exercise remains unknown. METHODS: Thirty-four MS patients were
randomized into a sedentary control group (SED, n = 11) and 2 exercise groups
that performed 12 weeks of a high intensity interval (HITR, n = 12) or high
intensity continuous cardiovascular training (HCTR, n = 11), both in combination
with resistance training. M.vastus lateralis fiber cross sectional area (CSA) and
proportion, knee-flexor/extensor strength, body composition, maximal endurance
capacity and self-reported physical activity levels were assessed before and
after 12 weeks. RESULTS: Compared to SED, 12 weeks of high intensity exercise
increased mean fiber CSA (HITR: +21 +/- 7%, HCTR: +23 +/- 5%). Furthermore, fiber
type I CSA increased in HCTR (+29 +/- 6%), whereas type II (+23 +/- 7%) and IIa
(+23 +/- 6%,) CSA increased in HITR. Muscle strength improved in HITR and HCTR
(between +13 +/- 7% and +45 +/- 20%) and body fat percentage tended to decrease
(HITR: -3.9 +/- 2.0% and HCTR: -2.5 +/- 1.2%). Furthermore, endurance capacity
(Wmax +21 +/- 4%, time to exhaustion +24 +/- 5%, VO2max +17 +/- 5%) and lean
tissue mass (+1.4 +/- 0.5%) only increased in HITR. Finally self-reported
physical activity levels increased 73 +/- 19% and 86 +/- 27% in HCTR and HITR,
respectively. CONCLUSION: High intensity cardiovascular exercise combined with
resistance training was safe, well tolerated and improved muscle contractile
characteristics and endurance capacity in MS. TRIAL REGISTRATION:
ClinicalTrials.gov NCT01845896.
PMID- 26418224
TI - Molecularly imprinted polymers for the solid-phase extraction of four
fluoroquilones from milk and lake water samples.
AB - A method based on molecular crowding and ionic liquids as reaction solvents has
been used for the synthesis of molecularly imprinted polymers. Levofloxacin was
selected as the template, polymethyl methacrylate was the molecular crowding
agent, and 1-butyl-3-methylimidazolium tetrafluoroborate (ionic liquid) was
selected as the reaction solvent and porogen. The optimized proportion for the
mixed porogen was dimethyl sulfoxide/ionic liquid/polymethyl methacrylate 1:1.6:5
in chloroform (150 mg mL(-1) ). The morphology and chemical composition of
levofloxacin imprinted polymers were assessed by scanning electron microscopy and
Fourier transform infrared spectroscopy. The absorption experiments demonstrated
that the levofloxacin imprinted polymers possess high selective recognition
property to levofloxacin and analogs, including enrofloxacin, ciprofloxacin and
gatifloxacin, which all belong to fluoroquinolones. An extraction method using
levofloxacin imprinted polymers as sorbent followed by high-performance liquid
chromatography analysis was optimized for the determination of four
fluoroquinolones in milk and lake water samples. Under the optimized conditions,
good linearity was observed in a range of 5-1000 ng g(-1) with the limit of
detection between 0.3 and 0.5 ng g(-1) for the four fluoroquinolones. The
recoveries at three spiked levels ranged 82.4-98.3% with the relative standard
deviation <=4.9.
PMID- 26418225
TI - The end of RIPK1-RIPK3-MLKL-mediated necroptosis in acetaminophen-induced
hepatotoxicity?
PMID- 26418226
TI - Gender-specific associations of sleep duration with uncontrolled blood pressure
in middle-aged patients.
AB - OBJECTIVE: The present study was designed to evaluate the associations between
sleep duration and uncontrolled blood pressure in a hospital-based sample of
middle-aged adults. METHODS: Between March 2012 and December 2012, a cross
sectional survey was conducted among the hypertensive outpatients of Anzhen
Hospital and a community hospital in Beijing, China. Eligible participants were
adults aged 35-55 years with an established diagnosis of hypertension and had
been on standard antihypertensive drug treatment for at least 6 months. An
interviewer-led questionnaire was used to collect the participants' demographic,
lifestyle and dietary information, as well as medical histories. Usual sleep
durations were categorized as <7 h, 7-8 h and >8 h per night. Logistic regression
models were used to assess gender-specific associations between sleep duration
and uncontrolled hypertension, with adjustment for age, gender, family history,
diabetes, smoking, alcohol consumption and physical activity. RESULTS: A total of
3038 participants were finally investigated. Among them, 1569 (51.6%) patients
had their blood pressure uncontrolled. In men, no significant association was
found between sleep duration categories and uncontrolled hypertension. In women,
compared with those sleeping <7 h, longer sleepers tended to have a lower risk of
uncontrolled hypertension for sleeping 7-8 hours (odds ratio [OR] 0.537, 95%
confidence interval [CI], 0.370-0.780) and sleeping >8 h (OR 0.316, 95% CI, 0.202
0.494), respectively. CONCLUSION: Modest associations between short sleep
duration and uncontrolled hypertension were seen in middle-aged women but not in
men in the hypertensive population.
PMID- 26418227
TI - Dielectric Elastomer Based "Grippers" for Soft Robotics.
AB - The use of few stiff fibers to control the deformation of dielectric elastomer
actuators, in particular to break the symmetry of equi-biaxial lateral strain in
the absence of prestretch, is demonstrated. Actuators with patterned fibers are
shown to evolve into unique shapes upon electrical actuation, enabling novel
designs of gripping actuators for soft robotics.
PMID- 26418228
TI - Using Ion Imaging to Measure Velocity Distributions in Surface Scattering
Experiments.
AB - We present a new implementation of ion imaging for the study of surface
scattering processes. The technique uses a combination of spatial ion imaging
with laser slicing and delayed pulsed extraction. The scattering velocities of
interest are parallel to the imaging plane, allowing speed and angular
distributions to be extracted from a single image. The first results of direct
scattering of N2 from a clean, single-crystal Au(111) surface are reported, and
the speed resolution is shown to be competitive with current state-of-the-art
time-of-flight methods for velocity measurements while providing simultaneous
measurements of in-plane angular distributions.
PMID- 26418229
TI - NUP98-HOXA9 bearing therapy-related myeloid neoplasm involves myeloid-committed
cell and induces HOXA5, EVI1, FLT3, and MEIS1 expression.
AB - INTRODUCTION: Chromosomal rearrangements involving NUP98 gene have been
associated with human leukemias such as de novo AML, therapy-related AML (t-AML),
myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). Genetic
fusion NUP98-HOXA9, caused by t(7;11)(p15;p15), is a recurrent cytogenetic
alteration in de novo acute myeloid leukemia (AML) usually found in young Asian
patients and its description in therapy-related myeloid neoplasms (t-MN) is rare.
Only one Asian case with molecular demonstration of the NUP98-HOXA9 fusion has
been reported in therapy-related leukemia. NUP98-HOXA9 leukemogenic mechanism is
derived from the transcription factor activity of the chimeric protein, which
enhances the expression of genes related to cellular differentiation arrest and
proliferation. PATIENTS AND METHODS: We studied a Caucasian woman with a therapy
related acute myeloid leukemia after Ewing's sarcoma. Molecular demonstration of
the genetic fusion NUP98-HOXA9 was performed by RT-PCR, and gene expression was
analyzed by real-time PCR, including four AML patients with MLL rearrangements
for comparative analysis. Cytologic and flow cytometric analysis was also carried
out. RESULTS: After cytologic and flow cytometric analysis diagnostics was
therapy-related myeloid neoplasm (t-MN). The major component of blasts in the
acute leukemia was with neutrophilic differentiation, but 13% erythroid lineage
blasts were also found. Cytogenetic and FISH analysis revealed t(7;11)(p15;p15)
and NUP98-HOXA9 fusion gene was demonstrated. Gene expression analysis showed
upregulation of EVI1 and MEIS1 in the index patient, both of them previously
related to a worst outcome. CONCLUSION: In this work, we include a detailed
molecular, clinical, cytological, and cytometric study of the second t-AML
bearing NUP98-HOXA9 genetic fusion.
PMID- 26418230
TI - Integration of Sentence-Level Semantic Information in Parafovea: Evidence from
the RSVP-Flanker Paradigm.
AB - During text reading, the parafoveal word was usually presented between 2 degrees
and 5 degrees from the point of fixation. Whether semantic information of
parafoveal words can be processed during sentence reading is a critical and long
standing issue. Recently, studies using the RSVP-flanker paradigm have shown that
the incongruent parafoveal word, presented as right flanker, elicited a more
negative N400 compared with the congruent parafoveal word. This suggests that the
semantic information of parafoveal words can be extracted and integrated during
sentence reading, because the N400 effect is a classical index of semantic
integration. However, as most previous studies did not control the word-pair
congruency of the parafoveal and the foveal words that were presented in the
critical triad, it is still unclear whether such integration happened at the
sentence level or just at the word-pair level. The present study addressed this
question by manipulating verbs in Chinese sentences to yield either a
semantically congruent or semantically incongruent context for the critical noun.
In particular, the interval between the critical nouns and verbs was controlled
to be 4 or 5 characters. Thus, to detect the incongruence of the parafoveal noun,
participants had to integrate it with the global sentential context. The results
revealed that the N400 time-locked to the critical triads was more negative in
incongruent than in congruent sentences, suggesting that parafoveal semantic
information can be integrated at the sentence level during Chinese reading.
PMID- 26418231
TI - Validation and Extension of the Prolonged Mechanical Ventilation Prognostic Model
(ProVent) Score for Predicting 1-Year Mortality after Prolonged Mechanical
Ventilation.
AB - RATIONALE: Prognostic models can inform management decisions for patients
requiring prolonged mechanical ventilation. The Prolonged Mechanical Ventilation
Prognostic model (ProVent) score was developed to predict 1-year mortality in
these patients. External evaluation of such models is needed before they are
adopted for routine use. OBJECTIVES: The goal was to perform an independent
external validation of the modified ProVent score and assess for spectrum
extension at 14 days of mechanical ventilation. METHODS: This was a retrospective
cohort analysis of patients who received prolonged mechanical ventilation at the
University of Iowa Hospitals. Patients who received 14 or more days of mechanical
ventilation were identified from a database. Manual review of their medical
records was performed to abstract relevant data including the four model
variables at Days 14 and 21 of mechanical ventilation. Vital status at 1 year was
checked in the medical records or the social security death index. Logistic
regressions examined the associations between the different variables and
mortality. Model performance at 14 to 20 days and 21+ days was assessed for
discrimination by calculating the area under the receiver operating
characteristic curve, and calibration was assessed using the Hosmer-Lemeshow
goodness-of-fit test. MEASUREMENTS AND MAIN RESULTS: A total of 180 patients (21+
d) and 218 patients (14-20 d) were included. Overall, 75% were surgical patients.
One-year mortality was 51% for 21+ days and 32% for 14 to 20 days of mechanical
ventilation. Age greater than 65 years was the strongest predictor of mortality
at 1 year in all cohorts. There was no significant difference between predicted
and observed mortality rates for patients stratified by ProVent score. There was
near-perfect specificity for mortality in the groups with higher ProVent scores.
Areas under the curve were 0.69 and 0.75 for the 21+ days and the 14 to 20 days
cohorts respectively. P values for the Hosmer-Lemeshow statistics were 0.24 for
21+ days and 0.22 for 14 to 20 days. CONCLUSIONS: The modified ProVent model was
accurate in our cohort. This supports its geographic and temporal
generalizability. It can also accurately identify patients at risk of 1-year
mortality at Day 14 of mechanical ventilation, but additional confirmation is
required. Further studies should explore the implications of adopting the model
into routine use.
PMID- 26418232
TI - CHILDHOOD MALTREATMENT AND THE COURSE OF DEPRESSIVE AND ANXIETY DISORDERS: THE
CONTRIBUTION OF PERSONALITY CHARACTERISTICS.
AB - BACKGROUND: We investigated the effect of childhood maltreatment on predicting
the 4-year course of depressive and anxiety disorders and the possible mediating
role of personality characteristics in the association between childhood
maltreatment and illness course. METHODS: Longitudinal data in a large sample of
participants with baseline depressive and/or anxiety disorders (n = 1,474, 18-65
years) were collected in the Netherlands Study of Depression and Anxiety. At
baseline, childhood maltreatment was assessed with a semistructured interview.
Personality trait questionnaires (Neuroticism-Extroversion-Openness Five Factor
Inventory, Mastery scale, and Leiden Index of Depression Sensitivity), recent
stressful life events (List of Threatening Experiences Questionnaire), and
psychosocial variables were administered. The Life Chart Interview was used to
determine the time to remission of depressive and/or anxiety disorders. RESULTS:
At baseline, 846 participants (57.4%) reported any childhood maltreatment.
Childhood maltreatment had a negative impact on psychosocial functioning and was
predictive of more unfavorable personality characteristics and cognitive
reactivity styles (P < 0.001). Childhood maltreatment was a significant predictor
of lower likelihood of remission of depressive and/or anxiety disorders (HR =
0.94, P < 0.001). High levels of neuroticism, hopelessness, external locus of
control, and low levels of extraversion were mediating the relationship between
childhood maltreatment and 4-year remission of depressive and anxiety disorders.
CONCLUSIONS: Certain personality characteristics are key players in the mechanism
linking childhood maltreatment to an adverse illness course of depressive and
anxiety disorders. Early interventions--reducing neuroticism and hopelessness,
and enhancing extraversion and locus of control--might contribute to a better
prognosis in a "high-risk" group of depressive and anxiety disorders.
PMID- 26418233
TI - Effectiveness of benzodiazepine premedication on recovery in day-case surgery: a
systematic review with meta-analysis.
AB - INTRODUCTION: Benzodiazepines are frequently used as a premedication. In day-case
surgery, anesthetists are reluctant to administer benzodiazepines preoperatively
for reasons of delayed recovery. However, premedication with benzodiazepines
might be beneficial regarding postoperative somatic symptoms/complaints (i.e.
time to recovery and postoperative side effects) and psychological phenomena.
EVIDENCE ACQUISITION: A systematic review with meta-analysis was performed using
all important search engines. Study methodological quality was assessed using
risk of bias tables. Mean differences (MD) and odds ratios (OR) were used for
continuous data (time to recovery and psychological phenomena) and categorical
data (postoperative somatic symptoms) respectively. Random effects modelling was
applied. Nineteen studies were included. Overall time to recovery was
significantly delayed in patients receiving benzodiazepines (MD 1.75; 95% CI 0.82
to 2.69) although time to discharge was not significantly affected. Postoperative
side effects were significantly reduced in patients receiving benzodiazepines (OR
0.47; 95% CI 0.36 to 0.63). Regarding psychological outcome, only anxiety could
be statistically analyzed showing no statistical difference (MD 1.47; 95% CI
1.01 to 3.96). EVIDENCE SYNTHESIS: Although overall time to recovery was
significantly prolonged by benzodiazepine premedication, withholding
premedication in day-case surgery patients is not justified for such reason, as
time to discharge was not negatively affected. Furthermore, benzodiazepines show
to have beneficial effects on postoperative side effects. CONCLUSIONS: For a firm
conclusion regarding psychological phenomena, more research is needed.
Anaesthetists should take into account this new evidence when they apply their
premedication regime in day-case surgery.
PMID- 26418234
TI - Mechanical ventilation on ECMO: unfinished business.
PMID- 26418235
TI - Prognostic and predictive immune gene signatures in breast cancer.
AB - PURPOSE OF REVIEW: Here, we focus on molecular biomarkers derived from
transcriptomic studies to summarize the recent advances in our understanding of
the mechanisms associated with differential prognosis and treatment outcome in
breast cancer. RECENT FINDINGS: Breast cancer is certainly immunogenic; yet it
has been historically resistant to immunotherapy. In the past few years, refined
immunotherapeutic manipulations have been shown to be effective in a significant
proportion of cancer patients. For example, drugs targeting the PD-1 immune
checkpoint have been proven to be an effective therapeutic approach in several
solid tumors including melanoma and lung cancer. Very recently, the activity of
such therapeutics has also been demonstrated in breast cancer patients. Pari
passu with the development of novel immune modulators, the transcriptomic
analysis of human tumors unveiled unexpected and paradoxical relationships
between cancer cells and immune cells. SUMMARY: This review examines our
understanding of the molecular pathways associated with intratumoral immune
response, which represents a critical step for the implementation of
stratification strategies toward the development of personalized immunotherapy of
breast cancer.
PMID- 26418236
TI - Matrix metalloproteinases -8 and -9 in the Airways, Blood and Urine During
Exacerbations of COPD.
AB - Matrix metalloproteinases (MMPs) are elevated in the airways and blood of COPD
patients, contributing to disease pathogenesis and tissue remodelling. However,
it is not clear if MMP levels in airways, blood and urine are related or if MMP
levels are related to disease severity or presence of exacerbations requiring
hospitalisation. Seventy-two patients requiring hospitalisation for COPD
exacerbations had serum, urine and sputum MMP-8, -9 and active MMP-9 measured by
ELISA and gelatin zymography on day one, five and four weeks later (recovery).
Clinical history, spirometry, COPD Assessment Test and MRC dyspnoea score were
obtained. Twenty-two stable COPD patients had MMP measurements one week apart.
During exacerbations, serum and urine MMP-9 were slightly elevated by 17% and 30%
compared with recovery values respectively (p = 0.001 and p = 0.026). MMP-8 was
not significantly changed. These MMP levels related to serum neutrophil numbers
but not to outcome of exacerbations, disease severity measures or smoking status.
In clinically stable patients, serum MMP levels did not vary significantly over 7
days, whereas urine MMPs varied by up to nine fold for MMP-8 (p = 0.003). Sputum,
serum and urine contained different MMP species and complexes. Median values for
sputum active MMP-9 were significantly different from serum (p = 0.035) and urine
(p = 0.024). Serum and urine MMPs are only modestly elevated during exacerbations
of COPD and unlikely to be useful biomarkers in this clinical setting. Airway,
serum and urine MMP levels are independent of each other in COPD patients.
Further, MMP levels are variable between patients and do not reflect airflow
obstruction.
PMID- 26418237
TI - LTP enhances synaptogenesis in the developing hippocampus.
AB - In adult hippocampus, long-term potentiation (LTP) produces synapse enlargement
while preventing the formation of new small dendritic spines. Here, we tested how
LTP affects structural synaptic plasticity in hippocampal area CA1 of Long-Evans
rats at postnatal day 15 (P15). P15 is an age of robust synaptogenesis when less
than 35% of dendritic spines have formed. We hypothesized that LTP might
therefore have a different effect on synapse structure than in adults. Theta
burst stimulation (TBS) was used to induce LTP at one site and control
stimulation was delivered at an independent site, both within s. radiatum of the
same hippocampal slice. Slices were rapidly fixed at 5, 30, and 120 min after
TBS, and processed for analysis by three-dimensional reconstruction from serial
section electron microscopy (3DEM). All findings were compared to hippocampus
that was perfusion-fixed (PF) in vivo at P15. Excitatory and inhibitory synapses
on dendritic spines and shafts were distinguished from synaptic precursors,
including filopodia and surface specializations. The potentiated response
plateaued between 5 and 30 min and remained potentiated prior to fixation. TBS
resulted in more small spines relative to PF by 30 min. This TBS-related spine
increase lasted 120 min, hence, there were substantially more small spines with
LTP than in the control or PF conditions. In contrast, control test pulses
resulted in spine loss relative to PF by 120 min, but not earlier. The findings
provide accurate new measurements of spine and synapse densities and sizes. The
added or lost spines had small synapses, took time to form or disappear, and did
not result in elevated potentiation or depression at 120 min. Thus, at P15 the
spines formed following TBS, or lost with control stimulation, appear to be
functionally silent. With TBS, existing synapses were awakened and then new
spines formed as potential substrates for subsequent plasticity.
PMID- 26418238
TI - An Evaluation of Prediction Equations for the 6 Minute Walk Test in Healthy
European Adults Aged 50-85 Years.
AB - OBJECTIVE: This study compared actual 6 minute walk test (6MWT) performance with
predicted 6MWT using previously validated equations and then determined whether
allometric modelling offers a sounder alternative to estimating 6MWT in adults
aged 50-80 years. METHODS: We compared actual 6MWT performance against predicted
6MWT in 125 adults aged 50-85 years (62 male, 63 female). In a second sample of
246 adults aged 50-85 years (74 male, 172 female), a new prediction equation for
6MWT performance was developed using allometric modelling. This equation was then
cross validated using the same sample that the other prediction equations were
compared with. RESULTS: Significant relationships were evident between 6MWT
actual and 6MWT predicted using all of the commonly available prediction
equations (all P<0.05 or better) with the exception of the Alameri et al
prediction equation (P>0.05). A series of paired t-tests indicated significant
differences between 6MWT actual and 6MWT predicted for all available prediction
equations (all P<0.05 or better) with the exception of the Iwama et al equation
(P = .540). The Iwama et al equation also had similar bias (79.8m) and a
coefficient of variation of over 15%. Using sample 2, a log-linear model
significantly predicted 6MWT from the log of body mass and height and age (P =
0.001, adjusted R2 = .526), predicting 52.6% of the variance in actual 6MWT. When
this allometric equation was applied to the original sample, the relationship
between 6MWT actual and 6MWT predicted was in excess of values reported for the
other previously validated prediction equations (r = .706, P = 0.001). There was
a significant difference between actual 6MWT and 6MWT predicted using this new
equation (P = 0.001) but the bias, standard deviation of differences and
coefficient of variation were all less than for the other equations. CONCLUSIONS:
Where actual assessment of the 6MWT is not possible, the allometrically derived
equation presented in the current study, offers a viable alternative which has
been cross validated and has the least SD of differences and smallest coefficient
of variation compared to any of the previously validated equations for the 6MWT.
PMID- 26418239
TI - Aseptic Meningitis Caused by Coxiella Burnetii.
AB - Acute Q fever can have multiple presentations but neurologic involvement is rare.
We describe the case of a 16-year-old female with severe headache and aseptic
meningitis with acute Coxiella burnetii infection.
PMID- 26418240
TI - Safe and Effective Prophylaxis with Bimonthly Intravenous Pentamidine in the
Pediatric Hematopoietic Stem Cell Transplant Population.
AB - BACKGROUND: Without prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops
in 5%-15% of pediatric hematopoietic stem cell transplant (HCT) patients with
mortality above 50%. Trimethoprim-sulfamethoxazole is a standard PCP prophylaxis;
pentamidine is frequently used as second-line prophylaxis because of trimethoprim
sulfamethoxazole's potential for cytopenias. Monthly intravenous (IV) pentamidine
has variable efficacy with PCP infection rates of 0%-10% in pediatric patients,
and higher breakthrough rates in those younger than 2 years. We hypothesized that
bimonthly (twice monthly) pentamidine might have equivalent safety and improved
efficacy; therefore, we conducted a retrospective analysis of bimonthly
pentamidine PCP prophylaxis. METHODS: We retrospectively reviewed records of all
pediatric HCT patients who received bimonthly IV pentamidine between December
2006 and June 2013, and collected data regarding demographics, clinical course,
prophylaxis rationale, laboratory values and adverse events. RESULTS: Between
December 2006 and June 2013, 111 pediatric HCT patients received bimonthly IV
pentamidine (574 doses, 8758 patient-days); 31 patients were younger than 2 years
at initiation. In the majority (53% of courses), pentamidine was initiated
because of cytopenias. Fourteen patients (12.6% of patients, 2.4% of doses)
experienced a side-effect prompting discontinuation, including 3 patients with
infusion-related hypotension/anaphylaxis and 3 with acute pancreatic dysfunction.
No patients [0% (95% confidence interval: 0-3.2)] developed PCP during or after
bimonthly IV pentamidine prophylaxis. CONCLUSIONS: Bimonthly IV pentamidine for
PCP prophylaxis in the HCT pediatric population has comparable safety to monthly
IV pentamidine and was highly effective, including in the very young. Bimonthly
IV pentamidine should be considered in pediatric patients as second-line PCP
prophylaxis.
PMID- 26418241
TI - Evaluation of Immune Response to Measles Component of MMR Vaccine in Children
with HIV Infection Receiving Antiretroviral Therapy.
AB - BACKGROUND: Children with HIV (CLHIV) respond poorly to primary immunization with
measles vaccine and those responding tend to lose protective titer of antibodies
by 2-3 years old. Revaccinating CLHIV after immune reconstitution with
antiretroviral therapy (ART) may result in good seroconversion, thereby
conferring them protection from measles. The objective was to study prevalence of
measles antibodies in CLHIV receiving ART before and after immunization with MMR
vaccine. METHODS: CLHIV in the age 5-18 years receiving ART for >6 months and
with CD 4 count >15% were included in this prospective study. Their serum was
assayed for IgG measles antibodies by qualitative immune-enzymatic determination
using enzyme linked immunosorbent assay. The subjects were then immunized with a
single dose of MMR vaccine. A repeat venous sample was assayed for measles
antibodies 8-12 weeks after immunization. RESULTS: Sixty-six subjects (46 males,
20 females, mean age 10.4 +/- 2.8 years) were enrolled. The mean duration of ART
was 3.4 +/- 1.5 years and median CD4 count 716.5 MU/L (interquartile range: 563.3
950). At enrollment, 16 (24.2%) subjects tested positive, 8 (12.1%) equivocal and
42 (63.6%) negative for measles antibodies. After 8-12 weeks of immunization, 62
(93.3%) tested positive, 1 (1.5%) equivocal, and 3 (4.5%) negative. There was no
difference among the seropositive and seronegative subjects postimmunization with
respect to age, sex, duration of ART, nutritional status, CD4 count, or WHO
clinical stage. No serious adverse reaction was observed to vaccination.
CONCLUSIONS: MMR vaccine leads to an excellent seroconversion to measles
component of vaccine in immune-reconstituted CLHIV.
PMID- 26418242
TI - Trends in Pertussis Diagnostic Testing in the United States, 1990 to 2012.
AB - BACKGROUND: Reports of pertussis have been increasing in the US since the 1990s,
and pertussis diagnostics have evolved during that time. Here, we describe
temporal changes in pertussis diagnostic practices in the US during 1990 to 2012
and discuss potential implications. METHODS: Pertussis cases reported through the
National Notifiable Diseases Surveillance System during 1990 to 2012 were
included in this analysis. Laboratory results were stratified by test type, case
classification, age group and case-patient state of residence. RESULTS: This
analysis included 291,290 cases with 64% (n = 186,766) reporting at least 1
pertussis laboratory result. Culture and direct fluorescent antibody were the
primary results reported during the early 1990s; however, polymerase chain
reaction (PCR) surpassed all other test types during the late 1990s and 2000s. By
2012, more than 91% of cases with known results were tested using PCR, either
alone or in combination with another test type. Before 2005, Massachusetts
reported 71% of serology results, but an increasing number of states reported
serologic results during 2005 to 2012. When stratified by age group, overall
testing trends persist. As of 2012, culture confirmation is used infrequently
across all ages, whereas the use of serology increases with age and is most
prevalent among adults aged >= 20 years. CONCLUSIONS: PCR has become the primary
diagnostic method, and serologic assays now are used in a majority of states.
Epidemiologic trends must be considered in the context of changing diagnostic
tests, and modifications to surveillance case definitions should be considered to
better reflect current testing practices.
PMID- 26418243
TI - Salmonella Osteomyelitis in Previously Healthy Children: Report of 4 Cases and
Review of the Literature.
AB - Salmonella osteomyelitis in children is an uncommon condition, typically
associated with hemoglobinopathies or other underlying disorders. Only few cases
have been reported in children without predisposing factors. We describe 4 cases
of Salmonella osteomyelitis in otherwise healthy children. Since treatment
duration is expected to be prolonged, the practice of direct inoculation of
aspirates into blood culture bottles appears to be essential for diagnosis and
targeted therapy.
PMID- 26418244
TI - Osteomyelitis Because of Mycobacterium Xenopi in an Immunocompetent Child.
AB - We present the case of a 6-year-old, immunocompetent boy with chronic
osteomyelitis of the calcaneus caused by Mycobacterium xenopi. Of note, typical
histopathology was not visible on the first biopsy and developed only later over
a period of 6 weeks, highlighting the difficult differential diagnosis of
osteomyelitis caused by nontuberculous mycobacteria.
PMID- 26418245
TI - Correction: Dynamic Changes of Post-Translationally Modified Forms of CXCL10 and
Soluble DPP4 in HCV Subjects Receiving Interferon-Free Therapy.
PMID- 26418246
TI - Coordinating Electron Transport Chains to an Electron Donor.
AB - Two electron transport chains (2 and 3) featuring two fullerenes with different
electron acceptor strengths have been synthesized, characterized, and coordinated
to a light harvesting/electron donating zinc porphyrin. Electrochemical assays
corroborate the redox gradients along the designed electron transport chains, and
complementary absorption and fluorescence titrations prove the assembly of ZnP-2
and ZnP-3 hybrids.
PMID- 26418247
TI - Genome Wide Association Analysis Reveals New Production Trait Genes in a Male
Duroc Population.
AB - In this study, 796 male Duroc pigs were used to identify genomic regions
controlling growth traits. Three production traits were studied: food conversion
ratio, days to 100 KG, and average daily gain, using a panel of 39,436 single
nucleotide polymorphisms. In total, we detected 11 genome-wide and 162 chromosome
wide single nucleotide polymorphism trait associations. The Gene ontology
analysis identified 14 candidate genes close to significant single nucleotide
polymorphisms, with growth-related functions: six for days to 100 KG (WT1, FBXO3,
DOCK7, PPP3CA, AGPAT9, and NKX6-1), seven for food conversion ratio (MAP2, TBX15,
IVL, ARL15, CPS1, VWC2L, and VAV3), and one for average daily gain (COL27A1).
Gene ontology analysis indicated that most of the candidate genes are involved in
muscle, fat, bone or nervous system development, nutrient absorption, and
metabolism, which are all either directly or indirectly related to growth traits
in pigs. Additionally, we found four haplotype blocks composed of suggestive
single nucleotide polymorphisms located in the growth trait-related quantitative
trait loci and further narrowed down the ranges, the largest of which decreased
by ~60 Mb. Hence, our results could be used to improve pig production traits by
increasing the frequency of favorable alleles via artificial selection.
PMID- 26418248
TI - PKC-Dependent GlyT1 Ubiquitination Occurs Independent of Phosphorylation:
Inespecificity in Lysine Selection for Ubiquitination.
AB - Neurotransmitter transporter ubiquitination is emerging as the main mechanism for
endocytosis and sorting of cargo into lysosomes. In this study, we demonstrate
PKC-dependent ubiquitination of three different isoforms of the glycine
transporter 1 (GlyT1). Incubation of cells expressing transporter with the PKC
activator phorbol ester induced a dramatic, time-dependent increase in GlyT1
ubiquitination, followed by accumulation of GlyT1 in EEA1 positive early
endosomes. This occurred via a mechanism that was abolished by inhibition of PKC.
GlyT1 endocytosis was confirmed in both retinal sections and primary cultures of
mouse amacrine neurons. Replacement of only all lysines in the N-and C-termini to
arginines prevented ubiquitination and endocytosis, displaying redundancy in the
mechanism of ubiquitination. Interestingly, a 40-50% reduction in glycine uptake
was detected in phorbol-ester stimulated cells expressing the WT-GlyT1, whereas
no significant change was for the mutant protein, demonstrating that endocytosis
participates in the reduction of uptake. Consistent with previous findings for
the dopamine transporter DAT, ubiquitination of GlyT1 tails functions as sorting
signal to deliver transporter into the lysosome and removal of ubiquitination
sites dramatically attenuated the rate of GlyT1 degradation. Finally, we showed
for the first time that PKC-dependent GlyT1 phosphorylation was not affected by
removal of ubiquitination sites, suggesting separate PKC-dependent signaling
events for these posttranslational modifications.
PMID- 26418250
TI - Impact of cyclin-dependent kinase CDK4 inhibition on eryptosis.
AB - BACKGROUND/AIMS: The cyclin-dependent kinase 4 (CDK4) participates in the
regulation of apoptosis of nucleated cells by altering transcriptional regulation
of genes governing cell proliferation and cell death. Similar to apoptosis of
nucleated cells, erythrocytes may enter eryptosis, which is characterized by cell
shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure at
the cell surface. As mature erythrocytes lack nuclei, acute stimulation of
eryptosis cannot result from altered gene expression. Eryptosis is triggered by
isotonic cell shrinkage following Cl- removal (replacement with the impermeant
organic anion gluconate) or by oxidative stress (exposure to 0.3 mM tertbutyl
hydroperoxide [tBOOH]). The present study explored whether CDK4 is expressed in
erythrocytes and whether the CDK4 inhibitors II (NSC625987) and III (ryuvidine)
influence eryptosis. METHODS: Western blotting was utilized for determination of
the presence of CDK4 protein in human erythrocytes, and FACS analysis to
determine Fluo3 fluorescence (reflecting cytosolic Ca2+), annexin-V-binding
(reflecting PS-exposure) and forward scatter (reflecting cell volume). RESULTS:
CDK4 protein was present in human erythrocytes. Cl- removal was followed by
decrease of forward scatter and increase of both annexin-V-binding and Fluo3
fluorescence, an effect significantly curtailed by CDK4 inhibitors II and III.
Furthermore, CDK4 inhibition blunted enhanced PS-exposure elicited by tBOOH
treatment. CONCLUSIONS: The present observations disclose the presence of CDK4
protein in human erythrocytes and the suppression of suicidal erythrocyte death
by pharmacological inhibition of CDK4.
PMID- 26418249
TI - Predicting Anticancer Drug Responses Using a Dual-Layer Integrated Cell Line-Drug
Network Model.
AB - The ability to predict the response of a cancer patient to a therapeutic agent is
a major goal in modern oncology that should ultimately lead to personalized
treatment. Existing approaches to predicting drug sensitivity rely primarily on
profiling of cancer cell line panels that have been treated with different drugs
and selecting genomic or functional genomic features to regress or classify the
drug response. Here, we propose a dual-layer integrated cell line-drug network
model, which uses both cell line similarity network (CSN) data and drug
similarity network (DSN) data to predict the drug response of a given cell line
using a weighted model. Using the Cancer Cell Line Encyclopedia (CCLE) and Cancer
Genome Project (CGP) studies as benchmark datasets, our single-layer model with
CSN or DSN and only a single parameter achieved a prediction performance
comparable to the previously generated elastic net model. When using the dual
layer model integrating both CSN and DSN, our predicted response reached a 0.6
Pearson correlation coefficient with observed responses for most drugs, which is
significantly better than the previous results using the elastic net model. We
have also applied the dual-layer cell line-drug integrated network model to fill
in the missing drug response values in the CGP dataset. Even though the dual
layer integrated cell line-drug network model does not specifically model
mutation information, it correctly predicted that BRAF mutant cell lines would be
more sensitive than BRAF wild-type cell lines to three MEK1/2 inhibitors tested.
PMID- 26418251
TI - Astrocyte elevated gene-1 increases invasiveness of NSCLC through up-regulating
MMP7.
AB - BACKGROUND/AIMS: The aggressive manner of non-small cell lung cancer (NSCLC)
cells accounts for the majority of the lethality of the disease. Recently,
increased astrocyte elevated gene-1 (AEG-1) levels have been shown to closely
correlate with poor prognosis of NSCLC, whereas the underlying mechanisms are not
clear. METHODS: We examined the AEG-1 and matrix metalloproteinase 7 (MMP7)
levels in NSCLC tissues, compared to the paired adjacent non-tumor lung tissue.
We modulated AEG-1 levels in NSCLC cells, and examined its effects on MMP7 levels
by RT-qPCR, on cellular protein by Western blot, and on secreted protein by
ELISA. We also examined the cell invasiveness in AEG-1-modified NSCLC cells in a
transwell cell migration assay. We used specific signal pathway inhibitors to
treat AEG-1-modified NSCLC cells and examined its effects on MMP7. RESULTS: AEG-1
and MMP7 levels were both significantly increased in NSCLC tissues, compared to
the paired adjacent non-tumor lung tissue. The AEG-1 and MMP7 levels were
strongly correlated. Overexpression of AEG-1 in NSCLC cells significantly
increased MMP7 levels and cell invasiveness, while AEG-1 depletion in NSCLC cells
significantly decreased MMP7 levels and cell invasiveness. Application of a
specific MAPK-p42/p44 inhibitor, but not application of specific inhibitors for
MAPK-p38, PI3k/Akt, or JNK signaling pathways, to AEG-1-overexpressing NSCLC
cells substantially abolished the AEG-1-mediated MMP7 up regulation. CONCLUSION:
AEG-1 promotes NSCLC cell invasiveness through MAPK-p42/p44-dependent activation
of MMP7.
PMID- 26418252
TI - Stimulating effect of a newly synthesized sulfonamido-based gallate on articular
chondrocytes in vitro.
AB - BACKGROUND: The phenotype of chondrocyte is easy to be lost when expanded in
vitro by a process defined "dedifferentiation". Traditional growth factors such
as transforming growth factor (TGF-beta1) are effective in preventing of
dedifferentiation, but high costs and loss of activity limited their use. It is
of significance to find substitutes which can reduce dedifferentiation and
preserve chondrocytes phenotype to ensure sufficient differentiated cells for
further study. METHODS: We synthesized new type of sulfonamido-based gallates
named ZXHA-C and investigated its effect on primary articular chondrocytes of
rats. After preliminary screening by cytotoxicity test, ZXHA-C of 1.06 * 10-8,
1.06 * 10-7 and 1.06 * 10-6M were chosen for further studies. Cell proliferation,
morphology, viability, GAG synthesis and cartilage specific gene expression were
detected. Also the effects of ZXHA-C on Wnt/beta-catenin signaling pathway were
investigated. RESULTS: ZXHA-C could significantly promote chondrocytes growth.
And it could enhance ECM synthesis by up-regulating expression levels of
cartilage specific markers like aggrecan, collagen II and Sox9. Expression of
collagen I which marked chondrocytes dedifferentiation was also significantly
down-regulated after treated by ZXHA-C. Further exploration of the molecular
mechanism indicated that ZXHA-C activated the Wnt/beta-catenin signal pathway in
chondrocytes, as evidenced by up-regulated gene expression of beta-catenin, Wnt
4, cyclin D1 and Frizzled-2 and decreased glycogen synthase kinase 3beta (GSK
3beta). Among the various concentrations, ZXHA-C of 1.06 * 10-7 M showed the best
performance, which was close to positive control (group with TGF-beta1).
CONCLUSION: ZXHA-C might be potential a novel agent for the maintenances of
chondrocytes phenotype.
PMID- 26418253
TI - Placental growth factor promotes metastases of non-small cell lung cancer through
MMP9.
AB - BACKGROUND/AIMS: Neovascularization and invasion coordinate cancer metastases in
non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms
are poorly understood. Recently, a substantial role of placental growth factor
(PLGF) in cancer cell invasion has been acknowledged in several types of cancer,
whereas a possible involvement of PLGF in the metastases of NSCLC has not been
studied. METHODS: Here, we analyzed the levels of PLGF and matrix
metalloproteinase 9 (MMP9) in NSCLC specimens. We modified either PLGF or MMP9
levels in a NSCLC cell line A549, and examined the effects on the levels of MMP9
and PLGF. The cell invasiveness was quantified in a transwell cell migration
assay. Pathway inhibitors were applied to determine the molecular mechanisms
underlying the control of MMP9 by PLGF. RESULTS: We found that PLGF and MMP9
levels both significantly increased in the NSCLC specimens and were strongly
correlated. Overexpression of PLGF in NSCLC cells increased the levels of MMP9
and cell invasiveness, while inhibition of PLGF in NSCLC cells decreased the
levels of MMP9 and cell invasiveness. However, modification of MMP9 levels in
NSCLC cells did not alter the levels of PLGF. These data suggest that PLGF may
regulate MMP9 in NSCLC cells, but not vice versa. Moreover, inhibition of MMP9 in
PLGF-overexpressing NSCLC cells abolished the effects of PLGF on cell
invasiveness, suggesting that PLGF increases cell invasion via MMP9. Furthermore,
suppression of MAPK-p38, but not suppression of either MAPK-p42/p44, or PI3k, or
JNK signaling, substantially abolished the effect of PLGF on MMP9, suggesting
that PLGF may activate MMP9 via MAPK-p38 signaling pathway. CONCLUSION: PLGF
stimulated cancer invasion may be mediated through its effects on MMP9 activation
in NSCLC cells.
PMID- 26418254
TI - The mechanism of radiosensitization by YM155, a novel small molecule inhibitor of
survivin expression, is associated with DNA damage repair.
AB - BACKGROUND/AIMS: Survivin, a member of the inhibitor of apoptosis protein family,
is an attractive target for cancer therapy. We investigated the effects of YM155,
a small molecule inhibitor of survivin expression, on the radiosensitivity of
human non-small cell lung cancer (NSCLC) cell lines and elucidated a relationship
between the cellular localization of survivin and DNA double-strand break repair.
METHODS: The cellular distribution of survivin was determined by Western blotting
of subcellular fractions and by immunofluorescent staining in A549 NSCLC cells.
Radiation-induced DNA damage was evaluated based on histone H2AX phosphorylation
and foci formation. The relationship between the cellular localization of
survivin and DNA double-strand break repair was analyzed by Western blotting and
co-immunoprecipitations. RESULTS: YM155 down-regulated survivin expression in
NSCLC cells in a concentration- and time-dependent manner. An in vitro clonogenic
survival assay revealed that YM155 increased the sensitivity of NSCLC cells to
radiation. After irradiation, we observed a rapid accumulation of survivin in the
nucleus. An immunofluorescent analysis of histone x03B3;-H2AX demonstrated that
the inhibition of survivin expression by YM155 resulted in impaired DNA double
strand break repair. Co-immunoprecipitation assays using nuclear extracts
revealed an interaction between survivin, Ku70, x03B3;-H2AX, and DNA-PKcs.
Furthermore, S2056 autophosphorylation of DNA-PKcs was reduced in survivin
depleted cells. CONCLUSIONS: These results suggested that YM155 sensitized NSCLC
cells to radiation, at least in part by inhibiting DNA repair and enhancing
apoptosis via the down-regulation of survivin expression. YM155 pretreatment
inhibited DNA-PKcs autophosphorylation at S2056. Nuclear survivin was involved in
DNA double-strand break repair via interactions with members of the DNA double
strand break repair machinery.
PMID- 26418255
TI - The Underlying Social Dynamics of Paradigm Shifts.
AB - We develop here a multi-agent model of the creation of knowledge (scientific
progress or technological evolution) within a community of researchers devoted to
such endeavors. In the proposed model, agents learn in a physical-technological
landscape, and weight is attached to both individual search and social influence.
We find that the combination of these two forces together with random
experimentation can account for both i) marginal change, that is, periods of
normal science or refinements on the performance of a given technology (and in
which the community stays in the neighborhood of the current paradigm); and ii)
radical change, which takes the form of scientific paradigm shifts (or
discontinuities in the structure of performance of a technology) that is observed
as a swift migration of the knowledge community towards the new and superior
paradigm. The efficiency of the search process is heavily dependent on the weight
that agents posit on social influence. The occurrence of a paradigm shift becomes
more likely when each member of the community attaches a small but positive
weight to the experience of his/her peers. For this parameter region,
nevertheless, a conservative force is exerted by the representatives of the
current paradigm. However, social influence is not strong enough to seriously
hamper individual discovery, and can act so as to empower successful individual
pioneers who have conquered the new and superior paradigm.
PMID- 26418256
TI - Tissue Factor Noncoagulant Signaling: Mechanisms and Implications for Cell
Migration and Apoptosis.
AB - Tissue factor (TF) is a 47-kDa transmembrane glycoprotein and the main initiator
of the blood coagulation cascade. Binding to its ligand factor VIIa (FVIIa) also
initiates noncoagulant signaling with broad biological implications. In this
review, we discuss how TF interacts with other cell-surface proteins, which
affect biological functions such as cell migration and cell survival. A vast
number of publications have demonstrated the importance of TF-induced activation
of protease-activated receptors, but recently published research has indicated a
more complicated picture. As it has been discovered that TF interacts with
integrins and receptor tyrosine kinases, novel signaling mechanisms for the
TF/FVIIa complex have been presented. The knowledge of these new aspects of TF
signaling may, for instance, facilitate the development of new treatment
strategies for cancer and acute coronary syndromes, two examples of diseases
characterized by aberrant TF expression and signaling.
PMID- 26418257
TI - The Sound of a Buk (Korean Traditional Drum) Attenuates Anaphylactic Reactions by
the Activation of Estrogen Receptor-beta.
AB - BACKGROUND: Anaphylaxis is associated with systemic vasodilation that causes low
blood pressure and induces hypoxic brain damage. The sound of a Buk (Korean
traditional drum) is similar to the human heart beat and affects blood pressure,
heart rate, and the nervous system by increasing physiological excitation and
sympathetic nervous system activity. So, this study focused on the effect of Buk
music as a means of treating anaphylaxis. METHODS: Mice were given an
intraperitoneal injection of compound 48/80 (6.5 mg/kg, a mast cell
degranulator). After compound 48/80 injection, mice were exposed to Buk music and
white noise for 5 min in a sound isolation booth. The mortality rate was checked
over the next 40 min. Levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and
vascular endothelial growth factor (VEGF) in the serum and brain tissues were
analyzed by Western blotting, quantitative real-time PCR, and ELISA methods.
RESULTS: Exposure to Buk music significantly reduced compound 48/80-induced
mortality and histamine release, as well as HIF-1alpha and VEGF levels compared
with the compound 48/80 group or compound 48/80 and white noise group. Buk music
also reduced levels of tumor necrosis factor-alpha, and significantly increased
estrogen receptor-beta mRNA levels. CONCLUSION: These results indicate that Buk
music has potential for the treatment of anaphylaxis.
PMID- 26418258
TI - Diffusion of Hydration Water around Intrinsically Disordered Proteins.
AB - Hydration water dynamics around globular proteins have attracted considerable
attention in the past decades. This work investigates the hydration water
dynamics around partially/fully intrinsically disordered proteins and compares it
to that of the globular proteins via molecular dynamics simulations. The
translational diffusion of the hydration water is examined by evaluating the mean
square displacement and the velocity autocorrelation function, while the
rotational diffusion is probed through the dipole-dipole time correlation
function. The results reveal that the translational and rotational motions of
water molecules at the surface of intrinsically disordered proteins/regions are
less restricted as compared to those around globular proteins/ordered regions,
which is reflected in their higher diffusion coefficient and lower orientational
relaxation time. The restricted mobility of hydration water in the vicinity of
the protein leads to a sublinear diffusion in a heterogeneous interface. A
positive correlation between the mean number of hydrogen bonds and the diffusion
coefficient of hydration water implies higher mobility of water molecules at the
surface of disordered proteins, which is due to their higher number of hydrogen
bonds. Enhanced hydration water mobility around disordered proteins/regions is
also related to their higher hydration capacity, low hydrophobicity, and
increased internal protein motions. Thus, we generalize that the intrinsically
disordered proteins/regions are associated with higher hydration water mobility
as compared to globular protein/ordered regions, which may help to elucidate
their varied functional specificity.
PMID- 26418259
TI - Oral Nutritional Supplements and Taste Adherence in Malnourished Adults
Inpatients, Effect on Adhesion during Hospital Stance.
AB - AIM: The aim of our study was to evaluate a hypercaloric sweet milk-based oral
nutrition supplement in a prospective 3-day study designed to assess the taste
preferences of this oral nutritional supplement (ONS) in malnourished inpatients
and the influence on adherence in daily intake. METHODS: A total of 46 in
patients with recent weight loss were included in this study. One flavor
(chocolate, vanilla or strawberry) was administered each day in a random way to
each patient during 3 consecutive days. In the first 3 days, patients were asked
to fill 2 questionnaires intended for reflecting ONS tolerance and acceptance.
RESULTS: Sweet was better for chocolate flavor (3.9 +/- 2.4 points) than for
vanilla flavor (2.7 +/- 2.3 points; p < 0.02) and strawberry flavor (3.1 +/- 2.3
points; p < 0.01). Chocolate flavored ONSs were rated as having more aftertaste
(3.4 +/- 2.1 points) than vanilla (2.4 +/- 2.1 points; p < 0.01) and strawberry
(2.6 +/- 1.5 points; p < 0.03). Patients who chose chocolate took a total of 20.7
+/- 20.9 average bricks during hospitalization (1.95 +/- 0.2 per day), patients
who chose vanilla took 18.6 +/- 21.0 bricks (1.90 +/- 0.7 per day) and finally
patients who chose strawberry took 14.5 +/- 13.5 bricks during admission (1.78 +/
0.1 per day; p < 0.01). CONCLUSIONS: The taste preferences of all the ONSs are
similar although the consumption is high in chocolate flavored ONS during
hospitalization. Sweetness may have influenced this finding.
PMID- 26418261
TI - Mixed Wastewater Coupled with CO2 for Microalgae Culturing and Nutrient Removal.
AB - Biomass, nutrient removal capacity, lipid productivity and morphological changes
of Chlorella sorokiniana and Desmodesmus communis were investigated in mixed
wastewaters with different CO2 concentrations. Under optimal condition, which was
1:3 ratio of swine wastewater to second treated municipal wastewater with 5% CO2,
the maximum biomass concentrations were 1.22 g L-1 and 0.84 g L-1 for C.
sorokiniana and D. communis, respectively. Almost all of the ammonia and
phosphorus were removed, the removal rates of total nitrogen were 88.05% for C.
sorokiniana and 83.18% for D. communis. Lipid content reached 17.04% for C.
sorokiniana and 20.37% for D. communis after 10 days culture. CO2 aeration
increased intracellular particle numbers of both microalgae and made D. communis
tend to be solitary. The research suggested the aeration of CO2 improve the
tolerance of microalgae to high concentration of NH4-N, and nutrient excess
stress could induce lipid accumulation of microalgae.
PMID- 26418260
TI - Initial Health Assessments and HIV Screening under the Affordable Care Act.
AB - BACKGROUND: The Centers for Disease Control and Prevention (CDC) estimates that
156,300 (95% CI 144,100-165,900) Americans living with HIV in 2012 were unaware
of their infection. To increase knowledge of HIV status, CDC guidelines seek to
make HIV screening a routine part of medical care. This paper examines how
routinely California primary care providers test for HIV and how providers'
knowledge of California's streamlined testing requirements, use of sexual
histories, and having an electronic medical record prompt for HIV testing, relate
to test offers. METHODS: We surveyed all ten California health plans offered
under health reform's Insurance Exchange (response rate = 50%) and 322 primary
care providers to those plans (response rate = 19%) to assess use of HIV
screening and risk assessments. RESULTS: Only 31.7% of 60 responding providers
reported offering HIV tests to all or most new enrollees and only 8.8% offered an
HIV test of blood samples all or most of the time despite the California law
requiring that providers offer HIV testing of blood samples in primary care
settings. Twenty-eight of the 60 providers (46.6%) were unaware that California
had reduced barriers to HIV screening by eliminating the requirement for written
informed consent and pre-test counseling. HIV screening of new enrollees all or
most of the time was reported by 53.1% of the well-informed providers, but only
7.1% of the less informed providers, a difference of 46 percentage points (95%
CI: 21.0%-66.5%). Providers who routinely obtained sexual histories were 29
percentage points (95% CI: 0.2%-54.9%) more likely to screen for HIV all or most
of the time than those who did not ask sexual histories. CONCLUSION: Changing HIV
screening requirements is important, but not sufficient to make HIV testing a
routine part of medical care. Provider education to increase knowledge about the
changed HIV testing requirements could positively impact testing rates.
PMID- 26418263
TI - Audit of Research Data.
PMID- 26418262
TI - Germinal Center Kinases SmKIN3 and SmKIN24 Are Associated with the Sordaria
macrospora Striatin-Interacting Phosphatase and Kinase (STRIPAK) Complex.
AB - The striatin-interacting phosphatase and kinase (STRIPAK) complex is composed of
striatin, protein phosphatase PP2A and protein kinases that regulate development
in animals and fungi. In the filamentous ascomycete Sordaria macrospora, it is
required for fruiting-body development and cell fusion. Here, we report on the
presence and function of STRIPAK-associated kinases in ascomycetes. Using the
mammalian germinal center kinases (GCKs) MST4, STK24, STK25 and MINK1 as query,
we identified the two putative homologs SmKIN3 and SmKIN24 in S. macrospora. A
BLASTP search revealed that both kinases are conserved among filamentous
ascomycetes. The physical interaction of the striatin homolog PRO11 with SmKIN3
and SmKIN24 were verified by yeast two-hybrid (Y2H) interaction studies and for
SmKIN3 by co-Immunoprecipitation (co-IP). In vivo localization found that both
kinases were present at the septa and deletion of both Smkin3 and Smkin24 led to
abnormal septum distribution. While deletion of Smkin3 caused larger distances
between adjacent septa and increased aerial hyphae, deletion of Smkin24 led to
closer spacing of septa and to sterility. Although phenotypically distinct, both
kinases appear to function independently because the double-knockout strain
DeltaSmkin3/DeltaSmkin24 displayed the combined phenotypes of each single
deletion strain.
PMID- 26418264
TI - Identification of MicroRNAs in Zebrafish Spermatozoa.
AB - MicroRNAs (miRNAs) participate in almost all biological processes. Plenty of
evidences show that some testis- or spermatozoa-specific miRNAs play crucial
roles in the process of gonad and germ cell development. In this study, the
spermatozoa miRNA profiles were investigated through a combination of illumina
deep sequencing and bioinformatics analysis in zebrafish. Deep sequencing of
small RNAs yielded 11,820,680 clean reads. By mapping to the zebrafish genome, we
identified 400 novel and 204 known miRNAs that could be grouped into 104
families. Furthermore, we selected the six highest expressions of known miRNAs to
detect their expression patterns in different tissues by stem-loop quantitative
real-time polymerase chain reaction. We found that among the six miRNAs, dre-miR
202-5p displayed specific and high expression in zebrafish spermatozoa and
testis. Fluorescence in situ hybridization analysis indicated that dre-miR-202-5p
was predominantly expressed in all kind of germ cells at different
spermatogenetic stages, including spermatogonia and spermatozoa, but barely
expressed in the germ cells in the ovary. This sex-biased expression pattern
suggests that dre-miR-202-5p might be related to spermatogenesis and the
functioning of spermatozoa. The identification of miRNAs in zebrafish spermatozoa
and germ cells offers new insights into the spermatogenesis and spermatozoa in
the teleost and other vertebrates.
PMID- 26418265
TI - Pyridoxine deficiency in adult patients with status epilepticus.
AB - An 8-year-old girl treated at our facility for superrefractory status epilepticus
was found to have a low pyridoxine level at 5 MUg/L. After starting pyridoxine
supplementation, improvement in the EEG for a 24-hour period was seen. We decided
to look at the pyridoxine levels in adult patients admitted with status
epilepticus. We reviewed the records on patients admitted to the neurological ICU
for status epilepticus (SE). Eighty-one adult patients were identified with
documented pyridoxine levels. For comparison purposes, we looked at pyridoxine
levels in outpatients with epilepsy (n=132). Reported normal pyridoxine range is
>10 ng/mL. All but six patients admitted for SE had low normal or undetectable
pyridoxine levels. A selective pyridoxine deficiency was seen in 94% of patients
with status epilepticus (compared to 39.4% in the outpatients) which leads us to
believe that there is a relationship between status epilepticus and pyridoxine
levels.
PMID- 26418266
TI - Charge-transfer complex versus sigma-complex formed between TiO2 and
bis(dicyanomethylene) electron acceptors.
AB - A novel group of organic-inorganic hybrid materials is created by the combination
of titanium dioxide (TiO2) nanoparticles with bis(dicyanomethylene) (TCNX)
electron acceptors. The TiO2-TCNX complex is produced by the nucleophilic
addition reaction between a hydroxy group on the TiO2 surface and TCNX, with the
formation of a sigma-bond between them. The nucleophilic addition reaction
generates a negatively-charged diamagnetic TCNX adsorbate that serves as an
electron donor. The sigma-bonded complex characteristically shows visible-light
absorption due to interfacial charge-transfer (ICT) transitions. In this paper,
we report on another kind of complex formation between TiO2 and TCNX. We have
systematically studied the structures and visible-light absorption properties of
the TiO2-TCNX complexes, with changing the electron affinity of TCNX. We found
that TCNX acceptors with lower electron affinities form charge-transfer complexes
with TiO2 without the sigma-bond formation. The charge-transfer complexes show
strong visible-light absorption due to interfacial electronic transitions with
little charge-transfer nature, which are different from the ICT transitions in
the sigma-bond complexes. The charge-transfer complexes induce efficient light-to
current conversions due to the interfacial electronic transitions, revealing the
high potential for applications to light-energy conversions. Furthermore, we
demonstrate that the formation of the two kinds of complexes is selectively
controlled by the electron affinity of TCNX.
PMID- 26418267
TI - Depression or anxiety: which is best able to predict patterns of lateralisation
for the processing of emotional faces?
AB - Previous research has shown that both anxiety and depression are associated with
strength of lateralisation for the processing of emotive faces, although these
clinical measures have always been considered in separate studies. In the present
study, we measure depression and anxiety, within the same non-clinical sample,
and consider whether these variables can predict strength of lateralisation,
measured using the chimeric faces test. There are two key findings from this
study. First, for females only, anxiety is negatively associated with right
hemispheric superiority for processing of negative emotional expressions. Second,
there was only one finding for depression, showing a relationship with strength
of lateralisation for the processing of fearful faces that differed according to
sex.
PMID- 26418268
TI - S-palmitoylation and the regulation of NCX1.
PMID- 26418269
TI - Does ulnar nerve dislocation at the elbow cause neuropathy: What do we learn?
PMID- 26418270
TI - The Informatics Challenges Facing Biobanks: A Perspective from a United Kingdom
Biobanking Network.
AB - The challenges facing biobanks are changing from simple collections of materials
to quality-assured fit-for-purpose clinically annotated samples. As a result,
informatics awareness and capabilities of a biobank are now intrinsically related
to quality. A biobank may be considered a data repository, in the form of raw
data (the unprocessed samples), data surrounding the samples (processing and
storage conditions), supplementary data (such as clinical annotations), and an
increasing ethical requirement for biobanks to have a mechanism for researchers
to return their data. The informatics capabilities of a biobank are no longer
simply knowing sample locations; instead the capabilities will become a
distinguishing factor in the ability of a biobank to provide appropriate samples.
There is an increasing requirement for biobanking systems (whether in-house or
commercially sourced) to ensure the informatics systems stay apace with the
changes being experienced by the biobanking community. In turn, there is a
requirement for the biobanks to have a clear informatics policy and directive
that is embedded into the wider decision making process. As an example, the
Breast Cancer Campaign Tissue Bank in the UK was a collaboration between four
individual and diverse biobanks in the UK, and an informatics platform has been
developed to address the challenges of running a distributed network. From
developing such a system there are key observations about what can or cannot be
achieved by informatics in isolation. This article will highlight some of the
lessons learned during this development process.
PMID- 26418271
TI - An analysis of the outcomes of cervical cone biopsies performed in a low resource
setting.
AB - Following skills transfer to this low resource setting, we carried out a
descriptive analysis of the outcomes of all cone biopsies performed for women
with cervical intra-epithelial neoplasia 3 (CIN 3). We also compared two methods
of cone biopsy. All the women had follow-up smear tests at 6 and 18 months. There
were no cases of CIN 3 at follow-up. 80% had normal smears at 18 months and 20%
had CIN 1. Compared with knife cone biopsy, women who had an electric knife (hand
held diathermy blade) cone biopsy had a significantly smaller volume of mean
blood loss (55.5mls +/- 15.9 vs 153.3ml +/- 40, p < 0.001). With appropriate
skills transfer, women with CIN 3 in a low resource setting can be effectively
treated with conisation procedures. The diathermy knife is preferred to cold
knife because of its associated low blood loss.
PMID- 26418272
TI - Enzymatic Polymerization of Furan-2,5-Dicarboxylic Acid-Based Furanic-Aliphatic
Polyamides as Sustainable Alternatives to Polyphthalamides.
AB - Furan-2,5-dicarboxylic acid (FDCA)-based furanic-aliphatic polyamides can be used
as promising sustainable alternatives to polyphthalamides (semiaromatic
polyamides) and be applied as high performance materials with great commercial
interest. In this study, poly(octamethylene furanamide) (PA8F), an analog to
poly(octamethylene terephthalamide) (PA8T), is successfully produced via Novozym
435 (N435)-catalyzed polymerization, using a one-stage method in toluene and a
temperature-varied two-stage method in diphenyl ether, respectively. The
enzymatic polymerization results in PA8F with high weight-average molecular
weight (M(w)) up to 54000 g/mol. Studies on the one-stage enzymatic
polymerization in toluene indicate that the molecular weights of PA8F increase
significantly with the concentration of N435; with an optimal reaction
temperature of 90 degrees C. The temperature-varied, two-stage enzymatic
polymerization in diphenyl ether yields PA8F with higher molecular weights, as
compared to the one-stage procedure, at higher reaction temperatures. MALDI-ToF
MS analysis suggests that eight end groups are present in the obtained PA8F:
ester/amine, ester/ester, amine/amine, acid/amine, ester/acid, acid/acid,
ester/amide, and no end groups (cyclic). Compared to PA8T, the obtained PA8F
possesses a similar Tg and similar crystal structures, a comparable Td, but a
lower Tm.
PMID- 26418273
TI - Regulation of alkane degradation pathway by a TetR family repressor via an
autoregulation positive feedback mechanism in a Gram-positive Dietzia bacterium.
AB - n-Alkanes are ubiquitous in nature and serve as important carbon sources for both
Gram-positive and Gram-negative bacteria. Hydroxylation of n-alkanes by alkane
monooxygenases is the first and most critical step in n-alkane metabolism.
However, regulation of alkane degradation genes in Gram-positive bacteria remains
poorly characterized. We therefore explored the transcriptional regulation of an
alkB-type alkane hydroxylase-rubredoxin fusion gene, alkW1, from Dietzia sp. DQ12
45-1b. The alkW1 promoter was characterized and so was the putative TetR family
regulator, AlkX, located downstream of alkW1 gene. We further identified an
unusually long 48 bp inverted repeat upstream of alkW1 and demonstrated the
binding of AlkX to this operator. Analytical ultracentrifugation and
microcalorimetric results indicated that AlkX formed stable dimers in solution
and two dimers bound to one operator in a positive cooperative fashion
characterized by a Hill coefficient of 1.64 (+/- 0.03) [k(D) = 1.06 (+/- 0.16)
MUM, k(D) ' = 0.05 (+/- 0.01) MUM]. However, the DNA-binding affinity was
disrupted in the presence of long-chain fatty acids (C10-C24), suggesting that
AlkX can sense the concentrations of n-alkane degradation metabolites. A model
was therefore proposed where AlkX controls alkW1 expression in a metabolite
dependent manner. Bioinformatic analysis revealed that the alkane hydroxylase
gene regulation mechanism may be common among Actinobacteria.
PMID- 26418274
TI - Leptin levels are reduced by intravenous ghrelin administration and correlated
with cue-induced alcohol craving.
AB - Increasing evidence supports the role of appetite-regulating pathways, including
ghrelin and leptin, in alcoholism. This study tested the hypothesis that
intravenous exogenous ghrelin administration acutely decreases endogenous serum
leptin levels, and that changes in leptin levels negatively correlate with
alcohol craving. This was a double-blind, placebo-controlled human laboratory
study. Non-treatment-seeking, alcohol-dependent, heavy drinkers (n=45) were
randomized to receive intravenous ghrelin or placebo, followed by a cue
reactivity procedure, during which participants were exposed to neutral (juice)
and alcohol trial cues. There was a main effect for intravenous ghrelin
administration, compared with placebo, in reducing serum leptin levels (P<0.01).
Post hoc analysis showed significant differences in serum leptin levels at the
alcohol trial (P<0.05) that persisted at the end of the experiment (P<0.05). By
contrast, there were no significant differences in serum leptin levels at the
juice trial (P=not significant (NS)). The change of serum leptin level at the
alcohol trial correlated with the increase in alcohol urge (P<0.05), whereas urge
to drink juice was not correlated with the leptin change at the juice trial
(P=NS). These findings provide preliminary evidence of ghrelin-leptin cross-talk
in alcoholic individuals and suggest that their relationship may have a role in
alcohol craving.
PMID- 26418275
TI - Children with autism spectrum disorders, who improved with a luteolin-containing
dietary formulation, show reduced serum levels of TNF and IL-6.
AB - Autism spectrum disorders (ASDs) have been associated with brain inflammation as
indicated by microglia activation, as well as brain expression and increased
plasma levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF). Here we
report that serum levels of IL-6 and TNF were elevated (61.95 +/- 94.76 pg ml(-1)
and 313.8 +/- 444.3 pg ml(-1), respectively) in the same cohort of patients with
elevated serum levels of corticotropin-releasing hormone (CRH) and neurotensin
(NT), while IL-9, IL-31 and IL-33 were not different from controls. The elevated
CRH and NT levels did not change after treatment with a luteolin-containing
dietary formulation. However, the mean serum IL-6 and TNF levels decreased
significantly (P=0.036 and P=0.015, respectively) at the end of the treatment
period (26 weeks) as compared with levels at the beginning; these decreases were
strongly associated with children whose behavior improved the most after luteolin
formulation treatment. Our results indicate that there are distinct subgroups of
children within the ASDs that may be identifiable through serum levels of IL-6
and TNF and that these cytokines may constitute distinct prognostic markers for
at least the beneficial effect of luteolin formulation.
PMID- 26418276
TI - Effects of depressive symptoms and peripheral DAT methylation on neural
reactivity to alcohol cues in alcoholism.
AB - In alcohol-dependent (AD) patients, alcohol cues induce strong activations in
brain areas associated with alcohol craving and relapse, such as the nucleus
accumbens (NAc) and amygdala. However, little is known about the influence of
depressive symptoms, which are common in AD patients, on the brain's reactivity
to alcohol cues. The methylation state of the dopamine transporter gene (DAT) has
been associated with alcohol dependence, craving and depression, but its
influence on neural alcohol cue reactivity has not been tested. Here, we compared
brain reactivity to alcohol cues in 38 AD patients and 17 healthy controls (HCs)
using functional magnetic resonance imaging and assessed the influence of
depressive symptoms and peripheral DAT methylation in these responses. We show
that alcoholics with low Beck's Depression Inventory scores (n=29) had higher cue
induced reactivity in NAc and amygdala than those with mild/moderate depression
scores (n=9), though subjective perception of craving was higher in those with
mild/moderate depression scores. We corroborated a higher DAT methylation in AD
patients than HCs, and showed higher DAT methylation in AD patients with
mild/moderate than low depression scores. Within the AD cohort, higher
methylation predicted craving and, at trend level (P=0.095), relapse 1 year after
abstinence. Finally, we show that amygdala cue reactivity correlated with craving
and DAT methylation only in AD patients with low depression scores. These
findings suggest that depressive symptoms and DAT methylation are associated with
alcohol craving and associated brain processes in alcohol dependence, which may
have important consequences for treatment. Moreover, peripheral DAT methylation
may be a clinically relevant biomarker in AD patients.
PMID- 26418278
TI - Understanding P450-mediated Bio-transformations into Epoxide and Phenolic
Metabolites.
AB - Adverse drug reactions are commonly the result of cytochrome P450 enzymes (CYPs)
converting the drugs into reactive metabolites. Thus, information about the CYP
bioactivation of drugs would not only provide insight into metabolic stability,
but also into the potential toxicity. For example, oxidation of phenyl rings may
lead to either toxic epoxides or safer phenols. Herein, we demonstrate that the
potential to form reactive metabolites is encoded primarily in the properties of
the molecule to be oxidized. While the enzyme positions the molecule inside the
binding pocket (selects the site of metabolism), the subsequent reaction is only
dependent on the substrate itself. To test this hypothesis, we used this
observation as a predictor of drug inherent toxicity. This approach was used to
successfully identify the formation of reactive metabolites in over 100 drug
molecules. These results provide a new perspective on the impact of functional
groups on aromatic oxidation of drugs and their effects on toxicity.
PMID- 26418279
TI - Fingerprint Ridge Density as a Potential Forensic Anthropological Tool for Sex
Identification.
AB - In cases of partial or poor print recovery and lack of database/suspect print,
fingerprint evidence is generally neglected. In light of such constraints, this
study was designed to examine whether ridge density can aid in narrowing down the
investigation for sex identification. The study was conducted on the right-hand
index digit of 245 males and 246 females belonging to the Punjabis of Delhi
region. Five ridge density count areas, namely upper radial, radial, ulnar, upper
ulnar, and proximal, were selected and designated. Probability of sex origin was
calculated, and stepwise discriminant function analysis was performed to
determine the discriminating ability of the selected areas. Females were observed
with a significantly higher ridge density than males in all the five areas.
Discriminant function analysis and logistic regression exhibited 96.8% and 97.4%
accuracy, respectively, in sex identification. Hence, fingerprint ridge density
is a potential tool for sex identification, even from partial prints.
PMID- 26418277
TI - Pathophysiology of major depressive disorder: mechanisms involved in etiology are
not associated with clinical progression.
AB - Meta-analyses support the involvement of different pathophysiological mechanisms
(inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin
D) in major depressive disorder (MDD). However, it remains unknown whether
dysregulations in these mechanisms are more pronounced when MDD progresses toward
multiple episodes and/or chronicity. We hypothesized that four central
pathophysiological mechanisms of MDD are not only involved in etiology, but also
associated with clinical disease progression. Therefore, we expected to find
increasingly more dysregulation across consecutive stages of MDD progression. The
sample from the Netherlands Study of Depression and Anxiety (18-65 years)
consisted of 230 controls and 2333 participants assigned to a clinical staging
model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from
familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance
examined whether pathophysiological mechanism markers (interleukin (IL)-6, C
reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin
D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and
1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4).
Subsequently, pathophysiological differences across separate stages within those
at risk and with full-threshold MDD were examined. A linear increase of
inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease
of vitamin D (P<0.001) was found across the entire sample (for example, from
controls to those at risk and those with full-threshold MDD). Significant trends
of dysregulations across stages were present in analyses focusing on at-risk
individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no
linear trends were found in dysregulations for any of the mechanisms across more
progressive stages of full-threshold MDD. Our results support that the examined
pathophysiological mechanisms are involved in MDD's etiology. These same
mechanisms, however, are less important in clinical progression from first to
later MDD episodes and toward chronicity.
PMID- 26418280
TI - Gal-1 silenced trophoblast tumor cells (BeWo) show decreased syncytium formation
and different miRNA production compared to non-target silenced BeWo cells.
AB - Galectin-1 (gal-1), a member of the mammalian beta-galactoside-binding proteins,
exerts biological effects by recognition of glycan ligands, including those
involved in cell adhesion and growth regulation. In previous studies, we
demonstrated that gal-1 induces cell differentiation processes on the membrane of
choriocarcinoma cells BeWo, including the receptor tyrosine kinases (RTKs)
REarranged during Transfection (RET), Janus Kinase 2 (JAK2) and Vascular
endothelial growth factor receptor 3 (VEGFR3). Furthermore, Mitogen-Activated
Protein Kinases (MAPK) and serine/threonine kinases were phosphorylated by gal-1.
In addition, gal-1 in trophoblast cells in vitro induced syncytium formation
especially after concentration dependent stimulation of the cells with this
galectin. This is in contrast to MAPK-inhibitor U0126 that reduced syncytium
formation of BeWo cells. The aim of this study was to analyze the syncytium
formation abilities of BeWo cells that were gal-1 silenced. We found a
significantly reduced syncytium formation rate in gal-1 silenced BeWo cells. In
addition, these cells show a different miRNA expression profile. In summary, we
found that gal-1 is a major trigger for fusion processes in BeWo cells. This
function is accompanied by different regulation of miRNA synthesis in the BeWo
cell culture model.
PMID- 26418281
TI - Large-Area Polyimide/SWCNT Nanocable Cathode for Flexible Lithium-Ion Batteries.
AB - A large-area flexible polymer electrode is fabricated using a new type of
polyimide/single-walled carbon nanotube (SWCNT) nanocable composite. SWCNTs serve
as the current collector and conductive network, and polyimide nanoparticles
anchored on carbon nanotubes act as active materials. The electrode shows
superior rate performance, good cycling stability, and high flexibility.
PMID- 26418282
TI - On analysis of longitudinal clinical trials with missing data using reference
based imputation.
AB - Reference-based imputation (RBI) methods have been proposed as sensitivity
analyses for longitudinal clinical trials with missing data. The RBI methods
multiply impute the missing data in treatment group based on an imputation model
built using data from the reference (control) group. The RBI will yield a
conservative treatment effect estimate as compared to the estimate obtained from
multiple imputation (MI) under missing at random (MAR). However, the RBI analysis
based on the regular MI approach can be overly conservative because it not only
applies discount to treatment effect estimate but also posts penalty on the
variance estimate. In this article, we investigate the statistical properties of
RBI methods, and propose approaches to derive accurate variance estimates using
both frequentist and Bayesian methods for the RBI analysis. Results from
simulation studies and applications to longitudinal clinical trial datasets are
presented.
PMID- 26418283
TI - A semiflexible 64-channel receive-only phased array for pediatric body MRI at 3T.
AB - PURPOSE: To design, construct, and validate a semiflexible 64-channel receive
only phased array for pediatric body MRI at 3T. METHODS: A 64-channel receive
only phased array was developed and constructed. The designed flexible coil can
easily conform to different patient sizes with nonoverlapping coil elements in
the transverse plane. It can cover a field of view of up to 44 * 28 cm(2) and
removes the need for coil repositioning for body MRI patients with multiple
clinical concerns. The 64-channel coil was compared with a 32-channel standard
coil for signal-to-noise ratio and parallel imaging performances on different
phantoms. With IRB approval and informed consent/assent, the designed coil was
validated on 21 consecutive pediatric patients. RESULTS: The pediatric coil
provided higher signal-to-noise ratio than the standard coil on different
phantoms, with the averaged signal-to-noise ratio gain at least 23% over a depth
of 7 cm along the cross-section of phantoms. It also achieved better parallel
imaging performance under moderate acceleration factors. Good image quality
(average score 4.6 out of 5) was achieved using the developed pediatric coil in
the clinical studies. CONCLUSION: A 64-channel semiflexible receive-only phased
array has been developed and validated to facilitate high quality pediatric body
MRI at 3T. Magn Reson Med 76:1015-1021, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26418284
TI - Reduced integration and differentiation of the imitation network in autism: A
combined functional connectivity magnetic resonance imaging and diffusion
weighted imaging study.
AB - OBJECTIVE: Converging evidence indicates that brain abnormalities in autism
spectrum disorder (ASD) involve atypical network connectivity, but few studies
have integrated functional with structural connectivity measures. This multimodal
investigation examined functional and structural connectivity of the imitation
network in children and adolescents with ASD, and its links with clinical
symptoms. METHODS: Resting state functional magnetic resonance imaging and
diffusion-weighted imaging were performed in 35 participants with ASD and 35
typically developing controls, aged 8 to 17 years, matched for age, gender,
intelligence quotient, and head motion. RESULTS: Within-network analyses revealed
overall reduced functional connectivity (FC) between distributed imitation
regions in the ASD group. Whole brain analyses showed that underconnectivity in
ASD occurred exclusively in regions belonging to the imitation network, whereas
overconnectivity was observed between imitation nodes and extraneous regions.
Structurally, reduced fractional anisotropy and increased mean diffusivity were
found in white matter tracts directly connecting key imitation regions with
atypical FC in ASD. These differences in microstructural organization of white
matter correlated with weaker FC and greater ASD symptomatology. INTERPRETATION:
Findings demonstrate atypical connectivity of the brain network supporting
imitation in ASD, characterized by a highly specific pattern. This pattern of
underconnectivity within, but overconnectivity outside the functional network is
in contrast with typical development and suggests reduced network integration and
differentiation in ASD. Our findings also indicate that atypical connectivity of
the imitation network may contribute to ASD clinical symptoms, highlighting the
role of this fundamental social cognition ability in the pathophysiology of ASD.
PMID- 26418285
TI - Correlative Studies in Clinical Trials: A Position Statement From the
International Thyroid Oncology Group.
AB - OBJECTIVE: Patients with progressive thyroid cancer in distant metastatic sites
represent a population with a need for new therapeutic options. Aspiring to
improve the treatment of such patients, the objective of this position statement
from the International Thyroid Oncology Group (ITOG) is to clarify the importance
of incorporating high-quality correlative studies into clinical trials.
PARTICIPANTS: ITOG was formed to develop and support high-quality multicenter and
multidisciplinary clinical trials for patients with aggressive forms of thyroid
cancer. The Correlative Sciences Committee of the ITOG focuses on the quality and
types of correlative studies included in ITOG-associated clinical trials.
EVIDENCE: This document represents expert consensus from ITOG regarding this
issue based on extensive collective experience in clinical and translational
trials informed by basic science. CONSENSUS PROCESS: The Correlative Studies
Committee identified an international writing group representative of diverse
specialties, including basic sciences. Drafts were reviewed by all members of the
writing group, the larger committee, and the ITOG board. After consideration of
all comments by the writing group and modification of the document, the final
document was then approved by the authors and the ITOG board. CONCLUSIONS: High
quality correlative studies, which include variety in the types of correlates,
should be intrinsic to the design of thyroid cancer clinical trials to offer the
best opportunity for each study to advance treatment for patients with advanced
and progressive thyroid cancer.
PMID- 26418286
TI - Serial GH Measurement After Intravenous Catheter Placement Alone Can Detect
Levels Above Stimulation Test Thresholds in Children.
AB - CONTEXT: GH stimulation testing is limited by poor specificity and
reproducibility in identifying GH deficiency. Intravenous line placement (IVP) in
pediatrics may be a stimulus for GH secretion. OBJECTIVE: The objective of the
study was to determine whether the measurement of GH at baseline as well as 15
and 30 minutes after IVP detects additional patients with sufficient peak GH
concentrations who are not identified by a subsequent insulin tolerance test
(ITT). METHODS: The ITT protocol was modified to include GH measurement at the
time of IVP (t = 0) and 15 (t = 15) and 30 (t = 30) minutes later. Insulin was
administered at t = 30, and an ITT was performed as per standard protocols.
Children were grouped according to the indication for ITT: initial evaluation of
GH deficiency (group 1); and GH deficiency at transition to adulthood (group 2).
RESULTS: Ninety-seven patients were included (76 in group 1, 21 in group 2). Of
these, 27 (28%) had a peak GH concentration of 7 ng/mL or greater (19 in group 1,
eight in group 2) either after IVP or ITT. Thirteen subjects (11 in group 1, two
in group 2) had GH concentrations of 7 ng/mL or greater after IVP, without
exceeding this on a subsequent ITT. Among the 11 group 1 patients, three of these
GH peaks of 7 ng/mL or greater occurred at t = 0, 5 at t = 15, and 5 at t = 30,
including one patient who had a peak GH of 7 ng/mL or greater at all three time
points. CONCLUSION: Some children will not have a sufficient GH response to
pharmacological stimuli but will have a robust response to IVP. We recommend GH
measurement after IVP in children undergoing GH stimulation testing, particularly
when there is a delay between IVP and the administration of the pharmacological
stimulus.
PMID- 26418288
TI - How Does Water Wet a Surface?
AB - The adsorption and reactions of water on surfaces has attracted great interest,
as water is involved in many physical and chemical processes at interfaces. On
metal surfaces, the adsorption energy of water is comparable to the hydrogen bond
strength in water. Therefore, the delicate balance between the water-water and
the water-metal interaction strength determines the stability of water
structures. In such systems, kinetic effects play an important role and many
metastable states can form with long lifetimes, such that the most stable state
may not reached. This has led to difficulties in the theoretical prediction of
water structures as well as to some controversial results. The direct imaging
using scanning tunneling microscopy (STM) in ultrahigh vacuum at low temperatures
offers a reliable means of understanding the local structure and reaction of
water molecules, in particular when interpreted in conjunction with density
functional theory calculations. In this Account, a selection of recent STM
results on the water adsorption and dissociation on close-packed metal surfaces
is reviewed, with a particular focus on Ru(0001). The Ru(0001) surface is one
where water adsorbs intact in a metastable state at low temperatures and where
partially dissociated layers are formed at temperatures above ~150 K. First, we
will describe the structure of intact water clusters starting with the monomer up
to the monolayer. We show that icelike wetting layers do not occur on close
packed metal surfaces but instead hydrogen bonded layers in the form of a mixture
of pentagonal, hexagonal, and heptagonal molecular rings are observed. Second, we
will discuss the dissociation mechanism of water on Ru(0001). We demonstrate that
water adsorption changes from dissociative to molecular as a function of the
oxygen preadsorbed on Ru. Finally, we briefly review recent STM experiments on
bulk ice (Ih and Ic) and water adsorption on insulating thin films. We conclude
with an outlook illustrating the manipulation capabilities of STM in respect to
probe the proton and hydrogen dynamics in water clusters.
PMID- 26418287
TI - Epigenetic Alterations in Human Liver From Subjects With Type 2 Diabetes in
Parallel With Reduced Folate Levels.
AB - OBJECTIVE: Epigenetic variation may contribute to the development of complex
metabolic diseases such as type 2 diabetes (T2D). Hepatic insulin resistance is a
hallmark of T2D. However, it remains unknown whether epigenetic alterations take
place in the liver from diabetic subjects. Therefore, we investigated the genome
wide DNA methylation pattern in the liver from subjects with T2D and nondiabetic
controls and related epigenetic alterations to gene expression and circulating
folate levels. RESEARCH DESIGN AND METHODS: Liver biopsies were obtained from 35
diabetic and 60 nondiabetic subjects, which are part of the Kuopio Obesity
Surgery Study. The genome-wide DNA methylation pattern was analyzed in the liver
using the HumanMethylation450 BeadChip. RNA expression was analyzed from a subset
of subjects using the HumanHT-12 Expression BeadChip. RESULTS: After correction
for multiple testing, we identified 251 individual CpG sites that exhibit
differential DNA methylation in liver obtained from T2D compared with nondiabetic
subjects (Q < .05). These include CpG sites annotated to genes that are
biologically relevant to the development of T2D such as GRB10, ABCC3, MOGAT1, and
PRDM16. The vast majority of the significant CpG sites (94%) displayed decreased
DNA methylation in liver from subjects with T2D. The hypomethylation found in
liver from diabetic subjects may be explained by reduced folate levels. Indeed,
subjects with T2D had significantly reduced erythrocyte folate levels compared
with nondiabetic subjects. We further identified 29 genes that displayed both
differential DNA methylation and gene expression in human T2D liver including the
imprinted gene H19. CONCLUSIONS: Our study highlights the importance of
epigenetic and transcriptional changes in the liver from subjects with T2D.
Reduced circulating folate levels may provide an explanation for hypomethylation
in the human diabetic liver.
PMID- 26418289
TI - WITHDRAWN: Ceramic inlays for restoring posterior teeth.
PMID- 26418290
TI - Conductive Nanowires Templated by Molecular Brushes.
AB - In this paper, we report the fabrication of conductive nanowires using polymer
bottle brushes as templates. In our approach, we synthesized poly(2
dimethylamino)ethyl methacrylate methyl iodide quaternary salt brushes by two
step atom transfer radical polymerization, loaded them with palladium salt, and
reduced them in order to form metallic nanowires with average lengths and widths
of 300 and 20 nm, respectively. The obtained nanowires were deposited between
conductive gold pads and were connected to them by sputtering of additional pads
to form an electric circuit. We connected the nanowires in an electric circuit
and demonstrated that the conductivity of these nanowires is around 100 S.m(-1).
PMID- 26418291
TI - Kinesin-5: A Team Is Just the Sum of Its Parts.
AB - How the cell builds a spindle remains an open question. In this issue of
Developmental Cell, Shimamoto, Forth, and Kapoor (2015) show that kinesin-5 motor
ensembles can exert sliding forces that scale with microtubule overlap length.
This behavior could allow microtubule architecture-dependent modulation of force
and contribute to spindle self-organization.
PMID- 26418292
TI - Spore No More: Quality Control during Bacterial Development.
AB - In this issue of Developmental Cell, Tan et al. (2015) describe an elegant
mechanism functioning during sporulation in Bacillus subtilis. Their findings
suggest that quality control purges unfit spores via programmed cell death,
providing further insight into the utility of this phenomenon in unicellular
organisms.
PMID- 26418293
TI - The Role of Cell Plasticity in Tissue Repair: Adaptive Cellular Reprogramming.
AB - It is becoming clear that a radical change of cell identity of differentiated
cells in vivo, triggered by injury or other adversity, provides an essential
route to recovery for many different mammalian tissues. This process, which we
term adaptive cellular reprogramming, promotes regeneration in one of two ways:
by providing a transient class of repair cells or by directly replacing cells
lost during tissue damage. Controlling adaptive changes in cell fate in vivo in
order to promote the body's own cell therapy, particularly by pharmacology rather
than genetics, is likely to become an increasingly active area of future work.
PMID- 26418294
TI - Temporal-Spatial Resolution Fate Mapping Reveals Distinct Origins for Embryonic
and Adult Microglia in Zebrafish.
AB - Microglia are CNS resident macrophages, and they play important roles in neural
development and function. Recent studies have suggested that murine microglia
arise from a single source, the yolk sac (YS), yet these studies lack spatial
resolution to define the bona fide source(s) for microglia. Here, using light
induced high temporal-spatial resolution fate mapping, we challenge this single
source view by showing that microglia in zebrafish arise from multiple sources.
The embryonic/larval microglia originate from the rostral blood island (RBI)
region, the equivalent of mouse YS for myelopoiesis, whereas the adult microglia
arise from the ventral wall of dorsal aorta (VDA) region, a tissue also producing
definitive hematopoiesis in mouse. We further show that the VDA-region-derived
microglia are Runx1 dependent, but cMyb independent, and developmentally
regulated differently from the RBI region-derived microglia. Our study
establishes a new paradigm for investigating the development and function of
distinct microglia populations.
PMID- 26418295
TI - Microtubules Negatively Regulate Insulin Secretion in Pancreatic beta Cells.
AB - For glucose-stimulated insulin secretion (GSIS), insulin granules have to be
localized close to the plasma membrane. The role of microtubule-dependent
transport in granule positioning and GSIS has been debated. Here, we report that
microtubules, counterintuitively, restrict granule availability for secretion. In
beta cells, microtubules originate at the Golgi and form a dense non-radial
meshwork. Non-directional transport along these microtubules limits granule
dwelling at the cell periphery, restricting granule availability for secretion.
High glucose destabilizes microtubules, decreasing their density; such local
microtubule depolymerization is necessary for GSIS, likely because granule
withdrawal from the cell periphery becomes inefficient. Consistently, microtubule
depolymerization by nocodazole blocks granule withdrawal, increases their
concentration at exocytic sites, and dramatically enhances GSIS in vitro and in
mice. Furthermore, glucose-driven MT destabilization is balanced by new
microtubule formation, which likely prevents over-secretion. Importantly,
microtubule density is greater in dysfunctional beta cells of diabetic mice.
PMID- 26418297
TI - Lost in Translation: The Patient-Physician Relationship in the Molecular Era.
PMID- 26418296
TI - Measuring Pushing and Braking Forces Generated by Ensembles of Kinesin-5
Crosslinking Two Microtubules.
AB - The proper organization of the microtubule-based mitotic spindle is proposed to
depend on nanometer-sized motor proteins generating forces that scale with a
micron-sized geometric feature, such as microtubule overlap length. However, it
is unclear whether such regulation can be achieved by any mitotic motor protein.
Here, we employ an optical-trap- and total internal reflection fluorescence
(TIRF)-based assay to show that ensembles of kinesin-5, a conserved mitotic motor
protein, can push apart overlapping antiparallel microtubules to generate a force
whose magnitude scales with filament overlap length. We also find that kinesin-5
can produce overlap-length-dependent "brake-like" resistance against relative
microtubule sliding in both parallel and antiparallel geometries, an activity
that has been suggested by cell biological studies but had not been directly
measured. Together, these findings, along with numerical simulations, reveal how
a motor protein can function as an analog converter, "reading" simple geometric
and dynamic features in cytoskeletal networks to produce regulated force outputs.
PMID- 26418298
TI - Usability of the Clinical Care Classification System for Representing Nursing
Practice According to Specialty.
AB - This study examined the ability of the Clinical Care Classification system to
represent nursing record data across various nursing specialties. The data
comprised nursing care plan records from December 1998 to October 2008 in a
medical center. The total number of care plan documentation we analyzed was 2 060
178, and we used a process of knowledge discovery in datasets for data analysis.
The results showed that 75.42% of the documented diagnosis terms could be mapped
using the Clinical Care Classification system. However, a difference in nursing
terminology emerged among various nursing specialties, ranging from 0.1% for
otorhinolaryngology to 100% for colorectal surgery and plastic surgery. The top
five nursing diagnoses were identified as knowledge deficit, acute pain,
infection risk, falling risk, and bleeding risk, which were the most common
health problems in an acute care setting but not in non-acute care settings.
Overall, we identified a total of 21 established nursing diagnoses, which we
recommend adding to the Clinical Care Classification system, most of which are
applicable to emergency and intensive care specialties. Our results show that
Clinical Care Classification is useful for documenting patient's problems in an
acute setting, but we suggest adding new diagnoses to identify health problems in
specialty settings.
PMID- 26418299
TI - Accounting for Intraligand Interactions in Flexible Ligand Docking with a PMF
Based Scoring Function.
AB - We analyzed the frequency with which intraligand contacts occurred in a set of
1300 protein-ligand complexes [ Plewczynski et al. J. Comput. Chem. 2011 , 32 ,
742 - 755 .]. Our analysis showed that flexible ligands often form intraligand
hydrophobic contacts, while intraligand hydrogen bonds are rare. The test set was
also thoroughly investigated and classified. We suggest a universal method for
enhancement of a scoring function based on a potential of mean force (PMF-based
score) by adding a term accounting for intraligand interactions. The method was
implemented via in-house developed program, utilizing an Algo_score scoring
function [ Ramensky et al. Proteins: Struct., Funct., Genet. 2007 , 69 , 349 -
357 .] based on the Tarasov-Muryshev PMF [ Muryshev et al. J. Comput.-Aided Mol.
Des. 2003 , 17 , 597 - 605 .]. The enhancement of the scoring function was shown
to significantly improve the docking and scoring quality for flexible ligands in
the test set of 1300 protein-ligand complexes [ Plewczynski et al. J. Comput.
Chem. 2011 , 32 , 742 - 755 .]. We then investigated the correlation of the
docking results with two parameters of intraligand interactions estimation. These
parameters are the weight of intraligand interactions and the minimum number of
bonds between the ligand atoms required to take their interaction into account.
PMID- 26418300
TI - A Programmed DNA Marker Based on Bis(4-ethynyl-1,8-naphthalimide) and Three
Methane-Bridged Thiazole Orange.
AB - Two large conjugated naphthalimide derivatives with or without three-methane
bridged thiazole orange (TO3; i.e., compounds 1 a and 2 a, respectively) were
designed and synthesized. The fluorescence of the naphthalimide group in compound
1 a at lambda=532 nm initially decreased and that for the TO3 group at lambda=655
nm increased sequentially upon adding Salmon testes (St) DNA. In contrast,
without the TO3 group, the fluorescence intensity of compound 2 a monotonously
decreased in response to the addition of DNA. The non-monotonic change in the
fluorescence for compound 1 a could be divided into two linear sections with two
different wavelengths in the range of 0 4.0
(range = 2.5-7.0). The results of multiple linear regression predicting maternal
sensitivity, R(2) = .26, indicated that greater improvements in child-rearing
attitudes over the course of treatment predicted higher levels of maternal
sensitivity, beta = .33, whereas improvements in posttraumatic stress symptoms
over the course of treatment did not, beta = -.10. Mothers' attitudes regarding
parenting during the perinatal period may be a mechanism by which intervention
fosters healthy mother-infant relationship dynamics. Thus, parenting attitudes
are a worthy target of intervention in vulnerable families.
PMID- 26418309
TI - Prolonged Abusive Chest Compressions in an Infant: An Occult Form of Child Abuse:
Review of Hemodynamics.
AB - This is the case of a 4-month-old male infant whose mother sought medical care
because of poor feeding and low-grade temperature. The infant had no external
evidence of abuse, but chest radiographs showed multiple bilateral rib fractures.
There were no retinal hemorrhages. Investigation revealed that the father had
repeatedly squeezed the child to unconsciousness. The cardiopulmonary effects of
this form of abuse are restriction of respiration and reduced cardiac output.
This is an unusual case of occult child abuse.
PMID- 26418310
TI - Insulin-like growth factor I in cats: validation of an enzyme-linked
immunosorbent assay and determination of biologic variation.
AB - BACKGROUND: Insulin-like growth factor I (IGF-I) measurements are used in
veterinary medicine for diagnosing growth hormone disorders. IGF-I assays are
subject to interference by IGF-binding proteins (IGFBP) which may not be
efficiently removed by standard extraction methods. Adding excess IGF-II during
analysis may improve accuracy. OBJECTIVES: The purpose of the study was to
validate a commercial human IGF-I ELISA which uses excess IGF-II for feline
samples and to evaluate biologic variation. METHODS: Precision was determined by
calculating the coefficient of variation (CV). Accuracy was determined by
recovery after removal of IGFBP, addition of IGF-I, and linear dilution after the
addition of IGFBP. Biologic variation was determined by repeated sampling in 7
cats. RESULTS: There was interference by IGFBP in the high measuring range,
resulting in falsely low IGF-I concentrations. This was overcome by the addition
of high concentrations of IGF-II. Untreated serum had a measured/expected ratio
of 98-115% compared to serum where IGFBP had been removed. Recovery after the
addition of IGF-I was 83-112%. Inter- and intra-assay CVs ranged from 2.4% to
5.0% which is within the minimum acceptance criteria based on biologic variation.
The reference interval of IGF-I was wide (90-1207 ng/mL) and there was a
significant association between body weight and ln IGF-I (P < .000001).
CONCLUSIONS: This human ELISA is suitable for feline samples, but interfering
IGFBP can cause falsely low concentrations. It is recommended to dilute samples
such that IGF-I is < 28 ng/mL on the standard curve to grant for sufficient IGF
II for binding of interferent IGFBP.
PMID- 26418311
TI - Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen
Induced Inflammation by Targeting GATA-3.
AB - Mast cell (MC) degranulation is the foundation of the acute phase of allergic
rhinitis (AR). Previously, downregulation of GATA binding protein 3 (GATA-3) was
shown to suppress MC activation in an AR mouse model. Binding of microRNA-135a
(miR-135a) to GATA-3 was also observed, and overexpression of this miRNA
decreased GATA-3 mRNA and protein expression. However, the effects of miR-135a on
MCs during AR are currently unknown. In the present study, we utilized a
lentiviral (LV) vector to intranasally administer miR-135a to ovalbumin (OVA)
sensitized AR mice. Following miR-135a treatment, the total serum IgE
concentration observed during AR was significantly reduced. In the nasal mucosa,
the expression of T-box expressed in T cells (T-bet) was higher, whereas that of
GATA-3 was lower in the AR mice following miRNA treatment. Notably, during AR,
the ratio of type 1 T-helper cells (Th1) to type 2 (Th2) cells in the spleen is
unbalanced, favoring Th2. However, administering miR-135a to the AR mice appeared
to balance this ratio by increasing and decreasing the percentage of Th1 and Th2
cells, respectively. MiR-135a also appeared to strongly suppress the infiltration
of eosinophils and MCs into the nasal mucosa, and it was specifically localized
in the MCs, suggesting that its influence is modulated through regulation of GATA
3 in these cells. Additional work identifying the full therapeutic potential of
miR-135a in the treatment of AR and diseases involving allergen-induced
inflammation is warranted.
PMID- 26418312
TI - A Self-Assembled Albumin-Based Nanoprobe for In Vivo Ratiometric Photoacoustic pH
Imaging.
AB - A photoacoustic nanoprobe is self-assembled from human serum albumin and two
types of dye molecules, one is inert to pH and the other is pH sensitive. This
probe and the quantitative ratiometric photoacoustic pH imaging method are shown
to have high safety, be easy-to-operate, and have depth-independent accuracy for
real-time in vivo pH imaging of entire tumors. These features make them promising
for future cancer prognosis and therapeutic planning.
PMID- 26418314
TI - One Million Quantum States of Benzene.
AB - In this study, we compute all of the dynamically relevant vibrational quantum
states of benzene, using an "exact" quantum dynamics (EQD) methodology. Benzene
(C6H6), in addition to being a very large molecule for EQD (12 atoms, 30
vibrational modes), also has a very large number of vibrational states-around
10(6) in all, lying within 6500 cm(-1) of the ground state. The EQD methodology
developed here uses a phase space picture to optimize the truncation of a
harmonic oscillator basis-not only with respect to the molecular system of
interest but also with respect to the targeted spectral range. By employing
several such EQD calculations, targeted to different spectral ranges, a
"hybridized" data set is constructed that provides the most accurate results
everywhere. In particular, more than 500,000 states are converged to 15 cm(-1) or
better.
PMID- 26418313
TI - Clinical and Cognitive Characteristics Associated with Mathematics Problem
Solving in Adolescents with Autism Spectrum Disorder.
AB - Mathematics achievement in autism spectrum disorder (ASD) has been understudied.
However, the ability to solve applied math problems is associated with academic
achievement, everyday problem-solving abilities, and vocational outcomes. The
paucity of research on math achievement in ASD may be partly explained by the
widely-held belief that most individuals with ASD are mathematically gifted,
despite emerging evidence to the contrary. The purpose of the study was twofold:
to assess the relative proportions of youth with ASD who demonstrate giftedness
versus disability on applied math problems, and to examine which cognitive (i.e.,
perceptual reasoning, verbal ability, working memory) and clinical (i.e., test
anxiety) characteristics best predict achievement on applied math problems in ASD
relative to typically developing peers. Twenty-seven high-functioning adolescents
with ASD and 27 age- and Full Scale IQ-matched typically developing controls were
assessed on standardized measures of math problem solving, perceptual reasoning,
verbal ability, and test anxiety. Results indicated that 22% of the ASD sample
evidenced a mathematics learning disability, while only 4% exhibited mathematical
giftedness. The parsimonious linear regression model revealed that the strongest
predictor of math problem solving was perceptual reasoning, followed by verbal
ability and test anxiety, then diagnosis of ASD. These results inform our
theories of math ability in ASD and highlight possible targets of intervention
for students with ASD struggling with mathematics.
PMID- 26418316
TI - CLASSIFICATION OF ANXIETY DISORDERS COMORBID WITH MAJOR DEPRESSION: COMMON OR
DISTINCT INFLUENCES ON RISK?
AB - BACKGROUND: Anxiety and depression display frequent comorbidity. Individuals with
comorbid disorders also often have more extreme symptomatology than those with
single disorders. This correlation between comorbidity and severity poses an
interesting question: Are comorbid forms of anxiety and depression essentially
just more severe versions of the pure disorders? METHODS: In a large major
depression (MD) case-control sample of individuals from the China, Oxford and VCU
Experimental Research on Genetic Epidemiology project, we examined the patterns
of lifetime anxiety comorbidity (including generalized anxiety disorder--GAD,
panic disorder, and five phobia subtypes) among MD cases (N = 5,864) in this
population. Binary and multinomial logistic regression was used to estimate
associations between risk factors and outcomes including MD as well as latent
class membership, which were compared using continuation ratios. RESULTS: We
found a five-class solution to fit best, and each resulting class had a distinct
pattern of association with the tested risk factors. The use of continuation
ratios suggests that a class characterized by high endorsement of GAD is
comparable to a more severely affected "pure MD" group. The other three classes
(characterized by agoraphobia, various specific phobias, and by high endorsement
of all comorbid anxiety disorders, respectively) appear to differ meaningfully
from MD alone. CONCLUSIONS: Risk for MD resulting from environmental and
psychosocial factors may also predispose individuals to GAD, and less
consistently, other anxiety disorders. Presentations of MD with certain phobias
display distinguishably different patterns of risk, however, and are therefore
likely qualitatively distinct.
PMID- 26418318
TI - Declining Dioxin Concentrations in the Rhone River Basin, France, Attest to the
Effectiveness of Emissions Controls.
AB - Emission-control policies have been implemented in Europe and North America since
the 1990s for polychlorodibenzodioxins (PCDDs) and furans (PCDFs). To assess the
effect of these policies on temporal trends and spatial patterns for these
compounds in a large European river system, sediment cores were collected in
seven depositional areas along the Rhone River in France, dated, and analyzed for
PCDDs and PCDFs. Results show concentrations increase in the downstream direction
and have decreased temporally at all sites during the last two decades, with an
average decrease of 83% from 1992 to 2010. The time for a 50% decrease in
concentrations (t1/2) averaged 6.9+/-2.6 and 9.1+/-2.9 years for the sum of
measured PCDDs and PCDFs, respectively. Congener patterns are similar among cores
and indicate dominance of regional atmospheric deposition and possibly weathered
local sources. Local sources are clearly indicated at the most downstream site,
where concentrations of the most toxic dioxin, TCDD, are about 2 orders of
magnitude higher than at the other six sites. The relatively steep downward
trends attest to the effects of the dioxin emissions reduction policy in Europe
and suggest that risks posed to aquatic life in the Rhone River basin from
dioxins and furans have been greatly reduced.
PMID- 26418317
TI - Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR) and Neural
System Function during Facial Recognition: A Pilot Study.
AB - This study examined changes in prefrontal oxy-Hb levels measured by NIRS (Near
Infrared Spectroscopy) during a facial-emotion recognition task in healthy
adults, testing a mediational/moderational model of these variables. Fifty-three
healthy adults (male = 35, female = 18) aged between 22 to 37 years old (mean age
= 24.05 years old) provided saliva samples, completed a EMBU questionnaire
(Swedish acronym for Egna Minnen Betraffande Uppfostran [My memories of
upbringing]), and participated in a facial-emotion recognition task during NIRS
recording. There was a main effect of maternal rejection on RoxH (right frontal
activation during an ambiguous task), and a gene * environment (G * E)
interaction on RoxH, suggesting that individuals who carry the SL or LL genotype
and who endorse greater perceived maternal rejection show less right frontal
activation than SL/LL carriers with lower perceived maternal rejection. Finally,
perceived parenting style played a mediating role in right frontal activation via
the 5-HTTLPR genotype. Early-perceived parenting might influence neural activity
in an uncertain situation i.e. rating ambiguous faces among individuals with
certain genotypes. This preliminary study makes a small contribution to the
mapping of an influence of gene and behaviour on the neural system. More such
attempts should be made in order to clarify the links.
PMID- 26418319
TI - Serum levels of endocan correlate with the presence and severity of pre
eclampsia.
AB - BACKGROUND: Endocan, a cysteine-rich dermatan sulfate proteoglycan expressed by
endothelial cells, is seemed to be a new biomarker for endothelial dysfunction.
Pre-eclampsia (PE) is characterized by the new onset of hypertension, proteinuria
after 20 weeks of gestation, placental vascular remodeling, systemic vascular
inflammation and endothelial dysfunction. The aim of this study was to
investigate the relationship of PE and its severity with serum endocan levels.
METHODS: A cross-sectional study was performed. Serum was collected from women
with PE and normotensive controls. Serum endocan and tumor necrosis factor alpha
(TNF-alpha) concentrations were measured by a specific enzyme linked
immunosorbent assay. RESULTS: Patients with PE had significantly higher median
(interquartile range) endocan and mean TNF-alpha concentrations than controls
[20.04 (12.26) ng/mL vs 15.55 (6.19) ng/mL, p < 0.001 for endocan; 26.49 +/-
12.14 pg/mL vs 14.62 +/- 5.61 pg/mL, p < 0.001 for TNF-alpha; respectively].
Serum endocan concentrations were positively correlated with systolic blood
pressure (r = 0.618, p < 0.001), diastolic blood pressure (r = 0.608, p < 0.001),
the amount of 24-h proteinuria (r = 0.786, p < 0.001) and TNF-alpha (r = 0.474, p
< 0.001) in women with PE. In subgroup analysis, patients with severe PE had
significantly higher endocan concentrations than those with mild PE. Receiver
operating characteristic analysis of endocan was used to identify the patients
with PE and also discriminating between mild and severe PE. CONCLUSION: Serum
endocan concentrations were significantly elevated in women with PE versus
normotensive controls, and concentrations seem to be associated with the severity
of the disease.
PMID- 26418320
TI - An analysis of clinical characteristics and prognosis for patients with serum
alpha-fetoprotein-positive gastric cancer.
AB - AIM: The aim of this analysis was to investigate the clinical characteristics and
prognosis of patients with serum alpha-fetoproteinpositive gastric cancer (AFPGC)
in order to improve the diagnosis and treatment. METHODS: A retrospective
analysis was performed on the clinical characteristics and survival data of
patients with gastric cancer in our hospital between March 2007 and September
2012, to compare the clinical characteristics of patients with serum AFPGC to
those of patients with serum AFP-negative gastric cancer. A Cox regression model
was used to explore the prognosis factors for gastric cancer. RESULTS: The 106
patients with serum AFPGC accounted for 8.5% (106/1253) of all the patients
during the same period. There were poorer differentiation (64.2% vs. 54.0%),
later clinical stage (83.1% vs. 48.6% at III+IV stage), larger tumor volume
(78.3% vs. 57.9% with diameter>5 cm), and higher incidence of liver metastases
(14.2% vs. 2.8%) and lymph node metastasis (76.4% vs. 52.7%) in patients with
serum AFPGC than in those with serum AFP-negative gastric cancer (P<0.05). The 1
, 3-, and 5-year survival rates in patients with serum AFPGC were 52.8%, 31.3%,
and 19.8%, respectively, with a median survival time of 14 months, and those in
patients with serum alpha-fetoprotein-negative gastric cancer were 78.3%, 54.8%,
and 36.8%, respectively, with a median survival time of 40 months. Multivariate
Cox regression analysis showed that serum AFP positive (RR=2.70, 95%
CI:1.50~4.87) was one of the risk factors of prognosis for patients with gastric
cancer. CONCLUSION: It is more malignant in patients with serum AFPGC than in
those with serum alpha-fetoprotein-negative gastric cancer. There are later
clinical stage, poorer differentiation, larger tumor volume, and higher incidence
of metastasis to the liver and lymph nodes in patients with serum AFPGC, with low
survival rate and poor prognosis.
PMID- 26418321
TI - Effect observation of anti epileptic drugs on serum folic acid and vitamin B12 of
epileptic patients.
AB - AIM: Comparative analysis of the effect of antiepileptic drugs on the epileptic
(tonic clonic seizure type) patient's serum folate and vitamin B12
concentrations. METHODS: Consecutively, 84 cases from September 2010 to September
2014 from the Department of Internal Medicine of our hospital were considered to
diagnose as epilepsy nerve. Among which, 49 cases received anti epileptic drug
treatment (treatment group), 35 cases received treatment without anti epileptic
drugs (non-treatment group); At the same period, 42 nonepileptic patients
(control group) underwent the analysis of the difference of serum folate and
vitamin B12 concentrations of among the three groups of patients before the test,
and at the end of test with the contrast analysis of difference of clinical
efficiency and thrombosis rate. RESULTS: Serum folic acid level of patients in
the treatment group decreased significantly after test, vitamin B12 level was
significantly higher, the differences were statistically significant (P<0.05),
but folic acid and vitamin B12 concentration of non-treatment group and the
control group did not change, and the differences were not statistically
significant (P>0.05). Clinical efficiency of treatment group patients was
significantly higher than that of the non-treatment group; the incidence of
thrombosis was significantly lower than that of the non-treatment group, and the
difference was statistically significant (P<0.05). CONCLUSION: Antiepileptic
drugs can significantly improve clinical efficacy of the epilepsy tonic clonic
seizure type patients, which may be related to the decrease of serum levels of
folate and vitamin B12-increased concentration.
PMID- 26418322
TI - Focal cerebral ischemia and neurovascular protection: a bench-to-bedside update.
AB - PURPOSE OF REVIEW: To date, many pharmacological approaches, or combination of
approaches, have been applied to experimental models of focal cerebral ischemia
(FCI), but their translation to clinically effective agents has proved
unsuccessful. To date, only thrombolysis with recombinant tissue-type plasminogen
activator, or other 'clot-breaking' or 'clot-removal' approaches, have proved
effective for acute stroke. This review, therefore, focuses on the 'vascular'
phenomena involved in the development of FCI. RECENT FINDINGS: Recent advances in
the experimental literature on FCI describe the microvascular characteristics of
the ischemic penumbra, the consequences of cortical spreading depression on
impairing cerebral perfusion, and the potential neuroprotective mechanisms of
ischemic preconditioning via antithrombotic effects on the neurovascular unit.
SUMMARY: This review provides a perspective about the neurovascular components
contributing to the pathophysiology of FCI, and some relevant clinical strategies
available on the horizon that hold promise for improved cerebral perfusion in
FCI.
PMID- 26418324
TI - Recent research advances in eosinophilic esophagitis.
AB - PURPOSE OF REVIEW: Eosinophilic esophagitis (EoE) is a chronic allergic disease
triggered by food allergens with an increasing prevalence. This review highlights
recent research advances in EoE with a focus on the literature of the past 18
months. RECENT FINDINGS: The incidence of EoE in the black population is higher
than previously suggested. A novel locus spanning CAPN14 is associated with EoE.
Diagnostic tests utilizing an analysis of EoE-specific transcriptome have been
improved. Standardized EoE symptom score systems have been established. Treatment
trials show the promise and limitations of allergen avoidance, antiinflammatory
reagents, and anti-interleukin-13 antibodies. Insights into disease mechanisms
highlight the role of invariant natural killer T cells and group 2 innate immune
cells. Epithelial barrier protein desmoglein 1, bone morphogenetic protein
antagonist follistatin, neurotrophic tyrosine kinase receptor type 1, and CAPN14
have been defined as new potential therapeutic targets in EoE as regulators of
the inflammatory interleukin-13-axis. The role of IgG4 in the disease mechanisms
has been suggested. SUMMARY: Genetic predisposition influenced by environmental
factors increases EoE susceptibility. Research identifying the critical events
leading to allergen sensitization and the esophagus-specific responses that drive
EoE is evolving, and will lead to a better understanding of EoE and new
therapeutic approaches for the disease.
PMID- 26418323
TI - Epigenetics in allergic diseases.
AB - PURPOSE OF REVIEW: Allergic diseases are among the most prevalent chronic
diseases of childhood, affecting more than 7 million children in the United
States. Epidemiological evidence supports the idea that the inception of allergic
diseases is typically before the preschool years, even when chronic symptoms do
not emerge until adulthood. The role of epigenetic mechanisms (particularly DNA
methylation) in allergic disease is under active investigation because these
mechanisms are known to be at the interface of gene regulation, environmental
stimuli, and developmental processes, all of which are essential for the
pathogenesis for asthma and allergy. This article specifically reviews genome
wide DNA methylation studies in allergic disease. RECENT FINDINGS: Differential
DNA methylation at specific regions appears to be associated with concurrent
allergic disease. A few studies have identified methylation signatures predictive
of disease. SUMMARY: DNA methylation signatures have been shown to be associated
with several allergic disease phenotypes, typically concurrently with disease.
The few that have been found to precede diagnosis are especially interesting
because they highlight an early trajectory to disease.
PMID- 26418325
TI - Pathogenesis of Adrenal Aldosterone-Producing Adenomas Carrying Mutations of the
Na(+)/K(+)-ATPase.
AB - Aldosterone-producing adenoma (APA) is a major cause of primary aldosteronism,
leading to secondary hypertension. Somatic mutations in the gene for the alpha1
subunit of the Na(+)/K(+)-ATPase were found in about 6% of APAs. APA-related
alpha1 subunit of the Na(+)/K(+)-ATPase mutations lead to a loss of the pump
function of the Na(+)/K(+)-ATPase, which is believed to result in membrane
depolarization and Ca(2+)-dependent stimulation of aldosterone synthesis in
adrenal cells. In addition, H(+) and Na(+) leak currents via the mutant
Na(+)/K(+)-ATPase were suggested to contribute to the phenotype. The aim of this
study was to investigate the cellular pathophysiology of adenoma-associated
Na(+)/K(+)-ATPase mutants (L104R, V332G, G99R) in adrenocortical NCI-H295R cells.
The expression of these Na(+)/K(+)-ATPase mutants depolarized adrenal cells and
stimulated aldosterone secretion. However, an increase of basal cytosolic Ca(2+)
levels in Na(+)/K(+)-ATPase mutant cells was not detectable, and stimulation with
high extracellular K(+) hardly increased Ca(2+) levels in cells expressing L104R
and V332G mutant Na(+)/K(+)-ATPase. Cytosolic pH measurements revealed an
acidification of L104R and V332G mutant cells, despite an increased activity of
the Na(+)/H(+) exchanger. The possible contribution of cellular acidification to
the hypersecretion of aldosterone was supported by the observation that
aldosterone secretion of normal adrenocortical cells was stimulated by acetate
induced acidification. Taken together, mutations of the Na(+)/K(+)-ATPase
depolarize adrenocortical cells, disturb the K(+) sensitivity, and lower
intracellular pH but, surprisingly, do not induce an overt increase of
intracellular Ca(2+). Probably, the autonomous aldosterone secretion is caused by
the concerted action of several pathological signaling pathways and incomplete
cellular compensation.
PMID- 26418328
TI - Body Plethysmography is Not Helpful for COPD Diagnosis, Determination of
Severity, Phenotyping, nor Response to Therapy.
PMID- 26418327
TI - Quantitative Analysis of Vortical Blood Flow in the Thoracic Aorta Using 4D Phase
Contrast MRI.
AB - INTRODUCTION: Phase contrast MRI allows for the examination of complex
hemodynamics in the heart and adjacent great vessels. Vortex flow patterns seem
to play an important role in certain vascular pathologies. We propose two- and
three-dimensional metrics for the objective quantification of aortic vortex blood
flow in 4D phase contrast MRI. MATERIALS AND METHODS: For two-dimensional
vorticity assessment, a standardized set of 6 regions-of-interest (ROIs) was
defined throughout the course of the aorta. For each ROI, a heatmap of time
resolved vorticity values [Formula: see text] was computed. Evolution of minimum,
maximum, and average values as well as opposing rotational flow components were
analyzed. For three-dimensional analysis, vortex core detection was implemented
combining the predictor-corrector method with lambda2 correction. Strength,
elongation, and radial expansion of the detected vortex core were recorded over
time. All methods were applied to 4D flow MRI datasets of 9 healthy subjects, 2
patients with mildly dilated aorta, and 1 patient with aortic aneurysm. RESULTS:
Vorticity quantification in the 6 standardized ROIs enabled the description of
physiological vortex flow in the healthy aorta. Helical flow developed early in
the ascending aorta (absolute vorticity = 166.4+/-86.4 s-1 at 12% of cardiac
cycle) followed by maximum values in mid-systole in the aortic arch (240.1+/-45.2
s-1 at 16%). Strength, elongation, and radial expansion of 3D vortex cores
escalated in early systole, reaching a peak in mid systole (strength = 241.2+/
30.7 s-1 at 17%, elongation = 65.1+/-34.6 mm at 18%, expansion = 80.1+/-48.8 mm2
at 20%), before all three parameters similarly decreased to overall low values in
diastole. Flow patterns were considerably altered in patient data: Vortex flow
developed late in mid/end-systole close to the aortic bulb and no physiological
helix was found in the aortic arch. CONCLUSIONS: We have introduced objective
measures for quantification of vortical flow in 4D phase contrast MRI. Vortex
blood flow in the thoracic aorta could be consistently described in all healthy
volunteers. In patient data, pathologically altered vortex flow was observed.
PMID- 26418329
TI - Enhanced Intracellular Delivery and Tissue Retention of Nanoparticles by Mussel
Inspired Surface Chemistry.
AB - Nanomaterials have been broadly studied for intracellular delivery of diverse
compounds for diagnosis or therapy. Currently it remains challenging for
discovering new biomolecules that can prominently enhance cellular
internalization and tissue retention of nanoparticles (NPs). Herein we report for
the first time that a mussel-inspired engineering approach may notably promote
cellular uptake and tissue retention of NPs. In this strategy, the catechol
moiety is covalently anchored onto biodegradable NPs. Thus, fabricated NPs can be
more effectively internalized by sensitive and multidrug resistant tumor cells,
as well as some normal cells, resulting in remarkably potentiated in vitro
activity when an antitumor drug is packaged. Moreover, the newly engineered NPs
afford increased tissue retention post local or oral delivery. This biomimetic
approach is promising for creating functional nanomaterials for drug delivery,
vaccination, and cell therapy.
PMID- 26418330
TI - A CASE OF ACCIDENTAL OCULAR INJURY FROM COSMETIC LASER BURN.
AB - PURPOSE: To report the clinical course of a patient sustaining a ocular laser
injury from 1,064-nm Nd:YAG cosmetic laser machine. METHOD AND PATIENT: A 31-year
old beauty parlor aesthetician was operating an Nd:YAG cosmetic laser machine of
1,064 nm wavelength. However, the probe was held in the opposite direction, and
on firing, the laser shot fired into her left eye. The patient heard a "pop"
sound followed by immediate floaters and blurring of vision. Her clinical course
was followed for 6 weeks, with investigations including optical coherence
tomography, fluorescein angiogram, and Humphrey's visual field examination
performed. RESULTS: Optical coherence tomography taken over the injured area
showed thickened retina and preretinal hyperreflectivities. Fluorescein angiogram
showed hypofluorescence superonasal to the disk with late staining of vessels.
Humphrey's visual field showed a dense scotoma emanating from the blind spot. The
lesion eventually scarred down, and the patient's vision recovered. DISCUSSION:
The eye is the most susceptible body part to laser light injury. A review of
reported laser accidents revealed the majority to be ocular injuries. The retina
is particularly vulnerable, as laser light with wavelength between 400 nm and
1,400 nm is focused by the cornea and lens onto the retina, increasing the
retinal irradiance as a result. Most injuries were parafoveal, suggesting that
most injuries occurred during laser beam alignment. The prognosis is generally
favorable. As laser use becomes more widespread and its application increasingly
heterogeneous, regulation of laser use and monitoring of laser safety are crucial
but at the same time challenging.
PMID- 26418326
TI - RF9 Acts as a KISS1R Agonist In Vivo and In Vitro.
AB - RF9, a reported antagonist of the mammalian gonadotropin-inhibitory hormone
receptor, stimulates gonadotropin secretion in mammals. Recent studies have
suggested that the stimulatory effect of RF9 on gonadotropin secretion relies on
intact kisspeptin receptor (KISS1R) signaling, but the underlying mechanisms
remain to be elucidated. Using Chinese Hamster Ovary cells stably transfected
with KISS1R, we show that RF9 binds specifically to KISS1R, with a Kd of 1.6 *
10(-5)M, and stimulates an increase in intracellular calcium and inositol
phosphate accumulation in a KISS1R-dependent manner, with EC50 values of 3.0 *
10(-6)M and 1.6 * 10(-7)M, respectively. RF9 also stimulated ERK phosphorylation,
with a time course similar to that of kisspeptin-10. RFRP-3, the putative
endogenous ligand for NPFFR1, did not stimulate inositol phosphate accumulation
or pERK, nor did it alter responses to of kisspeptin-10 or RF9. In agreement with
these in vitro data, we found that RF9 stimulated a robust LH increase in Npffr1(
/-) mice, similar to that in wild-type littermates, whereas the stimulatory
effect of RF9 was markedly reduced in Kiss1r(-/-) and double Kiss1r(-/-)/Npfrr1(
/-) mice. The stimulatory effect of RF9 on LH secretion was restored by the
selective rescue of Kiss1r expression in GnRH neurons, in Kiss1r(-/-T) mice.
Taken together, our study demonstrates that RF9 acts primarily as a KISS1R
agonist, but not as an allosteric modulator, to stimulate LH secretion. Our
findings raise questions regarding the utility of RF9 for assessing NPFF1R
function and de-emphasize a predominant role of this signaling system in central
regulation of reproduction.
PMID- 26418331
TI - RECURRENCE OF VITELLIFORM LESIONS ASSOCIATED WITH TEMPORARY VISION LOSS IN BEST
VITELLIFORM MACULAR DYSTROPHY.
AB - PURPOSE: To describe visual acuity changes associated with several cycles of
accumulation, disappearance, and reaccumulation of vitelliform material in Best
disease, with fundus photographs, fluorescein angiograms, and optical coherence
tomography images documenting these stages. METHODS: Case report with 70 months
of follow-up using fundus photography, fluorescein angiography, and optical
coherence tomography to image the retina. A non-Hispanic white 33-year-old man
with Best disease (positive for a mutation in the BEST1 gene, namely
p.Tyr167Cys:c.500A>G). RESULTS: The patient had a history of choroidal
neovascularization (CNV) followed by scarring of the macula with sustained vision
loss of ~20/250 in the left eye when he was in his twenties. He subsequently
presented in his thirties with acute vision loss in the right eye 3 times during
a 70-month follow-up period. Each episode of vision loss in the right eye was
preceded by several months of reaccumulation of vitelliform material in the
macula apparent on fundus photographs, fluorescein angiograms, and optical
coherence tomography, but no evidence of CNV on presentation. Each of the three
episodes of vision loss in the right eye was followed by spontaneous gradual
improvement in visual acuity over the next several months, correlating with
decreasing amounts of the vitelliform material on clinical examination and fundus
photographs. After the third documented recovery of visual acuity, at a time of
stable vision, the patient developed CNV in the right eye, treated with
intravitreal ranibizumab. CONCLUSION: This case demonstrates that vitelliform
material can reaccumulate and resorb several times in Best disease, with
temporary visual acuity decline after each episode of vitelliform material
accumulation. There is a need for continued vigilance for the development of CNV
in patients presenting with acute vision loss, although this patient developed
CNV at a time of stable vision.
PMID- 26418332
TI - Measurement of Postmortem 1,5-anhydroglucitol in Vitreous Humor for Forensic
Diagnosis.
AB - In forensic diagnosis, postmortem blood glucose is known to be susceptible to
change after death. However, the 1,5-anhydroglucitol (1,5-AG) concentrations in
plasma and cerebrospinal fluid (CSF) reflect the mean blood glucose level for a
short period of time. In this study, we compared the postmortem 1,5-AG
concentrations in vitreous humor and CSF in 47 subjects to evaluate the utility
of this concentration in the vitreous humor for forensic diagnosis. The
postmortem 1,5-AG concentrations in vitreous humor (mean+/-SD: 20.2 +/- 8.7
MUg/mL) and CSF (16.8 +/- 8.7 MUg/mL) did not differ significantly and showed a
strong correlation (r(2) = 0.87, p < 0.01). These results suggest that the
vitreous humor 1,5-AG concentration provides useful information on the antemortem
blood glucose level, in addition to the HbA1c value and the CSF 1,5-AG
concentration.
PMID- 26418333
TI - Flow-induced focal adhesion remodeling mediated by local cytoskeletal stresses
and reorganization.
AB - Cells respond to fluid shear stress through dynamic processes involving changes
in actomyosin and other cytoskeletal stresses, remodeling of cell adhesions, and
cytoskeleton reorganization. In this study we simultaneously measured focal
adhesion dynamics and cytoskeletal stress and reorganization in MDCK cells under
fluid shear stress. The measurements used co-expression of fluorescently labeled
paxillin and force sensitive FRET probes of alpha-actinin. A shear stress of 0.74
dyn/cm(2) for 3 hours caused redistribution of cytoskeletal tension and
significant focal adhesion remodeling. The fate of focal adhesions is determined
by the stress state and stability of the linked actin stress fibers. In the
interior of the cell, the mature focal adhesions disassembled within 35-40 min
under flow and stress fibers disintegrated. Near the cell periphery, the focal
adhesions anchoring the stress fibers perpendicular to the cell periphery
disassembled, while focal adhesions associated with peripheral fibers sustained.
The diminishing focal adhesions are coupled with local cytoskeletal stress
release and actin stress fiber disassembly whereas sustaining peripheral focal
adhesions are coupled with an increase in stress and enhancement of actin
bundles. The results show that flow induced formation of peripheral actin bundles
provides a favorable environment for focal adhesion remodeling along the cell
periphery. Under such condition, new FAs were observed along the cell edge under
flow. Our results suggest that the remodeling of FAs in epithelial cells under
flow is orchestrated by actin cytoskeletal stress redistribution and structural
reorganization.
PMID- 26418334
TI - Survival impact of the Australian National Bowel Cancer Screening Programme.
AB - BACKGROUND: The Australian National Bowel Cancer Screening Program (NBCSP) has
been offering age-based faecal occult blood testing since 2006. With the rapid
expansion of this programme, the NBCSP will ultimately offer biennial screening
to all 50-74 years old by 2020. Participation rates remain low. Previous reports
have described an increased proportion of earlier stage cancers in patients with
NBCSP-detected tumours. METHODS: Data on consecutive patients enrolled into a
prospective, comprehensive, multidisciplinary database at six Victorian hospitals
were examined. Clinicopathologic and outcome data were compared for NBCSP and
symptomatic presentation patients. RESULTS: We identified 3743 patients that
presented with colorectal cancer (CRC) at participating hospitals since May 2006.
Of 1930 patients aged between 50 and 70 years, 141 (7.3%) had a NBCSP detected
cancer, 1441 (74.7%) presented with symptoms and 266 (13.8%) were diagnosed
through screening outside of the NBCSP. Based on the American Society of
Anaesthesiology score, the NBCSP patients were fitter. They had an earlier stage
of diagnosis and were more likely to be female and less likely to have
lymphovascular invasion or to present as an emergency. NBCSP detected patients
had a lower rate of recurrence (HR 0.17, P = 0.0001) and fewer deaths (HR 0.19, P
= 0.005). CONCLUSIONS: Patients with NBCSP-detected CRC have a markedly reduced
risk of CRC recurrence and death compared with patients with a symptomatic
presentation. The dominant driver of this appears to be earlier stage at
diagnosis. Increased promotion of the impact of the NBCSP, including data related
to the survival impact, should be undertaken to increase participation rates and
achieve further survival gains.
PMID- 26418336
TI - Synthesis and spectral investigation of some new hetaryl-substituted
hydroquinolinone derivatives.
PMID- 26418335
TI - Temporal cAMP Signaling Selectivity by Natural and Synthetic MC4R Agonists.
AB - The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed in
the brain, where it controls energy balance through pathways including alpha
melanocyte-stimulating hormone (alpha-MSH)-dependent signaling. We have reported
that the MC4R can exist in an active conformation that signals constitutively by
increasing cAMP levels in the absence of receptor desensitization. We asked
whether synthetic MC4R agonists differ in their ability to increase intracellular
cAMP over time in Neuro2A cells expressing endogenous MC4R and exogenous, epitope
tagged hemagglutinin-MC4R-green fluorescent protein. By analyzing intracellular
cAMP in a temporally resolved Forster resonance energy transfer assay, we show
that withdrawal of alpha-MSH leads to a quick reversal of cAMP induction. By
contrast, the synthetic agonist melanotan II (MTII) induces a cAMP signal that
persists for at least 1 hour after removal of MTII from the medium and cannot be
antagonized by agouti related protein. Similarly, in mHypoE-42 immortalized
hypothalamic neurons, MTII, but not alpha-MSH, induced persistent AMP kinase
signal, which occurs downstream of increased cAMP. By using a fluorescence
recovery after photobleaching assay, it appears that the receptor exposed to MTII
continues to signal after being internalized. Similar to MTII, the synthetic MC4R
agonists, THIQ and BIM-22511, but not LY2112688, induced prolonged cAMP signaling
after agonist withdrawal. However, agonist-exposed MC4R desensitized to the same
extent, regardless of the ligand used and regardless of differences in receptor
intracellular retention kinetics. In conclusion, alpha-MSH and LY2112688, when
compared with MTII, THIQ, and BIM-22511, vary in the duration of the acute cAMP
response, showing distinct temporal signaling selectivity, possibly linked to
specific cell compartments from which cAMP signals may originate.
PMID- 26418337
TI - Toward Highly Sensitive Polymer Photodetectors by Molecular Engineering.
AB - Modified 3,4-ethylenedioxythiophene is employed as the conjugated side chain in
conjugated polymers, which can significantly depress the dark current of the
polymer photodetectors with little associated decrease in photovoltaic
properties, thus enhanceing the detectivities. This approach can be applied to a
variety of conjugated polymers covering a photoresponse range from UV to NIR.
PMID- 26418338
TI - Silymarin Constituent 2,3-Dehydrosilybin Triggers Reserpine-Sensitive Positive
Inotropic Effect in Perfused Rat Heart.
AB - 2,3-dehydrosilybin (DHS) is a minor flavonolignan component of Silybum marianum
seed extract known for its hepatoprotective activity. Recently we identified DHS
as a potentially cardioprotective substance during hypoxia/reoxygenation in
isolated neonatal rat cardiomyocytes. This is the first report of positive
inotropic effect of DHS on perfused adult rat heart. When applied to perfused
adult rat heart, DHS caused a dose-dependent inotropic effect resembling that of
catecholamines. The effect was apparent with DHS concentration as low as 10 nM.
Suspecting direct interaction with beta-adrenergic receptors, we tested whether
DHS can trigger beta agonist-dependent gene transcription in a model cell line.
While DHS alone was unable to trigger beta agonist-dependent gene transcription,
it enhanced the effect of isoproterenol, a known unspecific beta agonist. Further
tests confirmed that DHS could not induce cAMP accumulation in isolated neonatal
rat cardiomyocytes even though high concentrations (>= 10 MUM) of DHS were
capable of decreasing phosphodiesterase activity. Pre-treatment of rats with
reserpine, an indole alkaloid which depletes catecholamines from peripheral
sympathetic nerve endings, abolished the DHS inotropic effect in perfused hearts.
Our data suggest that DHS causes the inotropic effect without acting as a beta
agonist. Hence we identify DHS as a novel inotropic agent.
PMID- 26418340
TI - Correction: Acceleration of the Glycolytic Flux by Steroid Receptor Coactivator-2
Is Essential for Endometrial Decidualization.
PMID- 26418339
TI - Exploring Muscle Activation during Nordic Walking: A Comparison between
Conventional and Uphill Walking.
AB - Nordic Walking (NW) owes much of its popularity to the benefits of greater energy
expenditure and upper body engagement than found in conventional walking (W).
Muscle activation during NW is still understudied, however. The aim of the
present study was to assess differences in muscle activation and physiological
responses between NW and W in level and uphill walking conditions. Nine expert
Nordic Walkers (mean age 36.8+/-11.9 years; BMI 24.2+/-1.8 kg/m2) performed 5
minute treadmill trials of W and NW at 4 km/h on inclines of 0% and 15%. The
electromyographic activity of seven upper body and five leg muscles and oxygen
consumption (VO2) were recorded and pole force during NW was measured. VO2 during
NW was 22.3% higher at 0% and only 6.9% higher at 15% than during W, while upper
body muscle activation was 2- to 15-fold higher under both conditions. Lower body
muscle activation was similarly increased during NW and W in the uphill
condition, whereas the increase in erector spinae muscle activity was lower
during NW than W. The lack of a significant increase in pole force during uphill
walking may explain the lower extra energy expenditure of NW, indicating less
upper body muscle activation to lift the body against gravity. NW seemed to
reduce lower back muscle contraction in the uphill condition, suggesting that
walking with poles may reduce effort to control trunk oscillations and could
contribute to work production during NW. Although the difference in extra energy
expenditure between NW and W was smaller in the uphill walking condition, the
increased upper body muscle involvement during exercising with NW may confer
additional benefit compared to conventional walking also on uphill terrains.
Furthermore, people with low back pain may gain benefit from pole use when
walking uphill.
PMID- 26418341
TI - Simvastatin and vitamin D for migraine prevention: A randomized, controlled
trial.
AB - OBJECTIVE: The aim of this work was to assess efficacy and tolerability of
simvastatin plus vitamin D for migraine prevention in adults with episodic
migraine. METHODS: We performed a randomized, double-blind, placebo-controlled
trial with a 12-week baseline period and 24-week intervention period in 57 adults
with episodic migraine. Participants were randomly assigned to simvastatin 20 mg
tablets twice-daily plus vitamin D3 1,000 international units capsules twice
daily or matching placebo tablets and capsules. RESULTS: Compared to placebo,
participants using simvastatin plus vitamin D3 demonstrated a greater decrease in
number of migraine days from the baseline period to intervention weeks 1 to 12: a
change of -8.0 (interquartile range [IQR]: -15.0 to -2.0) days in the active
treatment group versus +1.0 (IQR: -1.0 to + 6.0) days in the placebo group, p <
0.001; and to intervention weeks 13 to 24: a change of -9.0 (IQR: -13 to -5) days
in the active group versus +3.0 (IQR: -1.0 to + 5.0) days in the placebo group, p
< 0.001. In the active treatment group, 8 patients (25%) experienced 50%
reduction in the number of migraine days at 12 weeks and 9 (29%) at 24 weeks
postrandomization. In comparison, only 1 patient (3%) in the placebo group (p =
0.03) experienced such a reduction. Adverse events were similar in both active
treatment and placebo groups. INTERPRETATION: The results demonstrate that
simvastatin plus vitamin D is effective for prevention of headache in adults with
episodic migraine. Given statins' ability to repair endothelial dysfunction, this
economical approach may also reduce the increased risk for vascular diseases
among migraineurs.
PMID- 26418343
TI - Ionic Switch Induced by a Rectangular-Hexagonal Phase Transition in
Benzenammonium Columnar Liquid Crystals.
AB - We demonstrate switching of ionic conductivities in wedge-shaped liquid
crystalline (LC) ammonium salts. A thermoreversible phase transition between the
rectangular columnar (Colr) and hexagonal columnar (Colh) phases is used for the
switch. The ionic conductivities in the Colh phase are about four orders of
magnitude higher than those in the Colr phase. The switching behavior of
conductivity can be ascribed to the structural change of assembled ionic
channels. X-ray experiments reveal a highly ordered packing of the ions in the
Colr phase, which prevents the ion transport.
PMID- 26418342
TI - Inhibition of EHMT2 Induces a Robust Antiviral Response Against Foot-and-Mouth
Disease and Vesicular Stomatitis Virus Infections in Bovine Cells.
AB - The genetic regulatory network controlling the innate immune system is well
understood in many species. However, the role of the epigenetic mechanisms
underlying the expression of immunoregulatory genes is less clear, especially in
livestock species. Histone H3 lysine 9 dimethylation (H3K9me2) is an epigenetic
modification associated with transcriptional silencing within the euchromatin
regions. Euchromatic histone-lysine N-methyltransferase 2 (EHMT2; also known as
G9a) is a crucial enzyme responsible for regulating the dynamics of this
epigenetic modification. It has been shown that histone modifications play a role
in regulating type I interferon (IFN) response. In the present study, we
investigated the role of EHMT2 in the epigenetic regulation of bovine antiviral
innate immunity and explored its therapeutic potential against viral infections.
We evaluated the effects of pharmacological and RNAi-mediated inhibition of EHMT2
on the transcription of IFN-beta and other IFN-inducible antiviral genes, as well
as its effect on foot-and-mouth disease virus (FMDV) and vesicular stomatitis
virus (VSV) replication in bovine cells. We show that treatment of primary bovine
cells with the synthetic EHMT2 inhibitor (UNC0638) either before or shortly after
virus infection resulted in a significant increase in transcript levels of bovine
IFN-beta (boIFN-beta; 300-fold) and other IFN-inducible genes, including IFN
stimulated gene 15 (ISG-15), myxovirus resistance 1 (Mx-1), Mx-2, RIG-I, 2',5'
oligoadenylate synthetase 1 (OAS-1), and protein kinase R (PKR). Expression of
these factors correlated with a significant decrease in VSV and FMDV viral
titers. Our data confirm the involvement of EHMT2 in the epigenetic regulation of
boIFN-beta and demonstrate the activation of a general antiviral state after
EHMT2 inhibition.
PMID- 26418344
TI - PbS Quantum-Dot Depleted Heterojunction Solar Cells Employing CdS Nanorod Arrays
as the Electron Acceptor with Enhanced Efficiency.
AB - Depleted heterojunction (DH) solar cells have shown great potential in power
conversion. A 3-D DH structure was first designed and fabricated through a layer
by-layer spin-coating technique to increase the interfacial contact of p-type PbS
quantum dots (QDs) and n-type CdS nanorod arrays. As a result, a decent power
conversion efficiency of 4.78% in this structure was achieved, which is five
times the efficiency of a planar heterojunction structure of a similar thickness.
In the 3-D DH structure, n-type CdS nanorod arrays (NRs) were grown vertically as
electron acceptors, on which p-type PbS quantum dots were deposited as absorbing
materials in a layer-by-layer spin-coating fashion. The results are discussed in
view of effective transportation of electrons through CdS NRs than the hopping
transportation in large nanoparticle-based CdS film, the enlarged interfacial
area, and shortened carrier diffusion distance.
PMID- 26418345
TI - Exploring the reciprocal relationship between caregiver burden and the functional
health of frail older adults in China: A cross-lag analysis.
AB - The present study aimed to investigate the reciprocal relationship between
caregiver burden and care recipient dependence in activities of daily living
(ADLs) from the perspective of frail older adults and their family caregivers in
China. Data were derived from a sample of 469 older adult-caregiver dyads that
participated in both the 2010 and 2013 waves of the panel study Family Caregivers
for the Frail and Very Elderly: Well-Being and Needs in Shanghai. A two-wave
cross-lag analysis was used to examine the proposed model. ADL dependence in 2010
was a significant predictor of caregiver burden in 2013. Furthermore, caregiver
burden in 2010 was a significant predictor of ADL dependence in 2013. This
finding confirms the dyadic model of caregiver burden and care recipient well
being. Implications for interventions and policy to help frail older adults and
their family caregivers are discussed.
PMID- 26418346
TI - Hierarchical Polymer-Carbon Nanotube Hybrid Mesostructures by Crystallization
Driven Self-Assembly.
AB - Multistep crystallization-driven self-assembly has great potential to enable the
construction of sophisticated hybrid mesostructures. During the assembly
procedure, each step modifies the properties of the overall structure. Here, we
demonstrate the flexibility and efficiency of this approach by preparing polymer
carbon nanotube (CNT) hybrid mesostructures. We started by growing
polyferrocenyldimethylsilane (PFS) homopolymer crystals onto multiwalled CNTs.
This first step facilitated the redispersion of the coated CNTs in both polar (2
propanol) and nonpolar (decane) solvents. In the second step of hybrid
construction, a unimer solution of a PFS block copolymer was added into the PFS
CNT solution. The PFS coating on the CNT initiated the growth of elongated
micelles, resulting in structures that resembled hairy caterpillars. PFS-b-P2VP
(P2VP = poly-2-vinylpyridine) micelles were grown from the surface of PFS-CNT
hybrids in 2-propanol, and PFS-b-PI (PI = polyisoprene) micelles were grown from
these hybrids in decane. These micelles, by transmission electron microscopy were
seen to have an unusual wavy kinked structure, very different from the uniform
smooth structures normally formed by both block copolymers. For hybrids with PFS
b-PI micelles, cross-linking of the micelle coronas locked the whole structure in
place and allowed us to use the partial oxidation of PFS components to grow metal
nanoparticles in the core of these micelles. We finally investigated the
influence of the corona-forming block used to grow the micelles on the
wettability of films made from these mesostructures. Films formed with CNT
hybrids grafted with PFS-b-PI micelles were superhydrophobic (contact angle, 152
degrees ). In contrast, the surface of the films was much more hydrophilic
(contact angle, 54 degrees ) when they were prepared from CNT hybrids grafted
with PFS-b-P2VP micelles.
PMID- 26418347
TI - Preoperative vascular access evaluation for haemodialysis patients.
AB - BACKGROUND: Haemodialysis treatment requires reliable vascular access. Optimal
access is provided via functional arteriovenous fistula (fistula), which compared
with other forms of vascular access, provides superior long-term patency,
requires few interventions, has low thrombosis and infection rates and cost.
However, it has been estimated that between 20% and 60% of fistulas never mature
sufficiently to enable haemodialysis treatment. Mapping blood vessels using
imaging technologies before surgery may identify vessels that are most suitable
for fistula creation. OBJECTIVES: We compared the effect of conducting routine
radiological imaging evaluation for vascular access creation preoperatively with
standard care without routine preoperative vessel imaging on fistula creation and
use. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised
Register to 14 April 2015 through contact with the Trials' Search Co-ordinator
using search terms relevant to this review. SELECTION CRITERIA: We included
randomised controlled trials (RCTs) that enrolled adult participants (aged >= 18
years) with chronic or end-stage kidney disease (ESKD) who needed fistulas (both
before dialysis and after dialysis initiation) that compared fistula maturation
rates relating to use of imaging technologies to map blood vessels before fistula
surgery with standard care (no imaging). DATA COLLECTION AND ANALYSIS: Two
authors assessed study quality and extracted data. Dichotomous outcomes,
including fistula creation, maturation and need for catheters at dialysis
initiation, were expressed as risk ratios (RR) with 95% confidence intervals
(CI). Continuous outcomes, such as numbers of interventions required to maintain
patency, were expressed as mean differences (MD). We used the random-effects
model to measure mean effects. MAIN RESULTS: Four studies enrolling 450
participants met our inclusion criteria. Overall risk of bias was judged to be
low in one study, unclear in two, and high in one.There was no significant
differences in the number of fistulas that were successfully created (4 studies,
433 patients: RR 1.06, 95% CI 0.95 to 1.28; I2 = 76%); the number of fistulas
that matured at six months (3 studies, 356 participants: RR 1.11, 95% CI 0.98 to
1.25; I2 = 0%); number of fistulas that were used successfully for dialysis (2
studies, 286 participants: RR 1.12, 95% CI 0.99 to 1.28; I2 = 0%); the number of
patients initiating dialysis with a catheter (1 study, 214 patients: RR 0.66, 95%
CI 0.42 to 1.04); and in the rate of interventions required to maintain patency
(1 study, 70 patients: MD 14.70 interventions/1000 patient-days, 95% CI -7.51 to
36.91) between the use of preoperative imaging technologies compared with
standard care (no imaging). AUTHORS' CONCLUSIONS: Based on four small studies,
preoperative vessel imaging did not improve fistula outcomes compared with
standard care. Adequately powered prospective studies are required to fully
answer this question.
PMID- 26418348
TI - Do emotions or gender drive our actions? A study of motor distractibility.
AB - People's interaction with the social environment depends on the ability to attend
social cues with human faces being a key vehicle of this information. This study
explores whether directing the attention to gender or emotion of a face
interferes with ongoing actions. In two experiments, participants reached for one
of two possible targets by relying on one of two features of a face, namely,
emotion (Experiment 1) or gender (Experiment 2) of a non-target stimulus (a task
relevant distractor). Participants' reaching movements deviated toward the task
relevant distractor in both experiments. However, when attending to the gender of
the face the distractor effect was modulated by both gender (task-relevant
feature) and emotion (task-irrelevant feature), with the largest movement
deviation being observed toward angry male faces. Endogenous allocation of
attention toward faces elicits a competing motor response to the ongoing action
and the emotional content of the face contributes to this process at a more
automatic and implicit level.
PMID- 26418349
TI - The relationship between chitotriosidase activity and tuberculosis.
AB - Chitotriosidase, secreted by activated macrophages, is a biomarker of activated
macrophages. In this study, we explored whether chitotriosidase could be adopted
as a biomarker to evaluate the curative effect on tuberculosis (TB). Five
counties were randomly selected out of 122 counties/cities/districts in Hunan
Province, China. Our cases were all TB patients who were newly diagnosed or had
been receiving treatment at the Centers for Disease Control (CDCs) of these five
counties between April and August in 2009. Healthy controls were selected from a
community health facility in the Kaifu district of Changsha City after frequency
matching of gender and age with the cases. Chitotriosidase activity was evaluated
by a fluorometric assay. Categorical variables were analysed with the chi 2 test.
Measurement data in multiple groups were tested with analysis of variance and
least significant difference (LSD). Correlation between chitotriosidase activity
and the degree of radiological extent (DRE) was examined by Spearman's rank
correlation test. The average chitotriosidase activity levels of new TB cases, TB
cases with different periods of treatment (6 months) and the control group were
54.47, 34.77, 21.54, 12.73 and 10.53 nmol/h.ml, respectively. Chitotriosidase
activity in TB patients declined along with the continuity of treatment. The
chitotriosidase activity of both smear-positive and the smear-negative pulmonary
TB patients decreased after 6 months' treatment to normal levels (P < 0.05).
Moreover, chitotriosidase activity was positively correlated with DRE (r = 0.607,
P < 0.001). Our results indicate that chitotriosidase might be a marker of TB
treatment effects. However, further follow-up study of TB patients is needed in
the future.
PMID- 26418351
TI - Group B streptococcus infections of soft tissue and bone in California adults,
1995-2012.
AB - Group B streptococcus (GBS) is an increasing cause of disease in adults. We
present long-term trends in incidence of overall infections and identify
characteristics of patients with GBS cellulitis, bone and joint infections.
Active, population-based surveillance was conducted from 1995-2012 in three
California counties and the data were analysed retrospectively. All cases had
isolation of GBS from a normally sterile site. Cases of cellulitis were
classified based on clinical diagnosis. GBS bone or joint infection was defined
as isolation of GBS from a bone or joint or a diagnosis of osteomyelitis or
septic arthritis. Medical charts were reviewed for demographic and clinical
information. There were 3917 cases of GBS; the incidence of disease increased
from 5.8 to 8.3 cases/100 000 persons (P < 0.001) from 1995 to 2012. In adults
aged ?40 years, the overall incidence of GBS increased from 8.5 to 14.2 cases/100
000 (P < 0.001) persons during the study period. The incidence of cellulitis
increased from 1.6 to 3.8 cases/100 000 (P < 0.001), bone infection increased
from 0.7 to 2.6 cases/100 000 (P < 0.001), and the incidence of joint infection
remained approximately constant at an average rate of 1.0 case/100 000. The
highest incidence rates were observed in men, persons aged ?80 years, non
Hispanic blacks and Hispanics. Diabetes was the most common underlying condition
(51.2% cellulitis cases, 76.3% bone infections, 29.8% joint infections).
PMID- 26418350
TI - Determination of cut-off cycle threshold values in routine RT-PCR assays to
assist differential diagnosis of norovirus in children hospitalized for acute
gastroenteritis.
AB - Norovirus (NV) is an important cause of acute gastroenteritis in children, but is
also frequently detected in asymptomatic children, which complicates the
interpretation of NV detection results in both the clinical setting and
population prevalence studies. A total of 807 faecal samples from children aged
<5 years hospitalized for acute gastroenteritis were collected in Thai Binh,
Vietnam, from January 2011 to September 2012. Real-time RT-PCR was used to detect
and quantify NV-RNA in clinical samples. A bimodal distribution of cycle
threshold (Ct) values was observed in which the lower peak was assumed to
represent cases for which NV was the causal agent of diarrhoea, whereas the
higher peak was assumed to represent cases involving an alternative pathogen
other than NV. Under these assumptions, we applied finite-mixture modelling to
estimate a threshold of Ct <21.36 (95% confidence interval 20.29-22.46) to
distinguish NV-positive patients for which NV was the likely cause of diarrhoea.
We evaluated the validity of the threshold through comparisons with NV antigen
ELISA results, and comparisons of Ct values in patients co-infected with
rotavirus. We conclude that the use of an appropriate cut-off value in the
interpretation of NV real-time RT-PCR results may improve differential diagnosis
of enteric infections, and could contribute to improved estimates of the burden
of NV disease.
PMID- 26418352
TI - Our panel of experts highlight the most important research articles across the
spectrum of topics relevant to the field of regenarative medicine.
PMID- 26418353
TI - Study of Environment Lifestyle and Fibroids (SELF): Advancing the Field of
Fibroid Epidemiology.
PMID- 26418354
TI - Did Socioeconomic Inequality in Self-Reported Health in Chile Fall after the
Equity-Based Healthcare Reform of 2005? A Concentration Index Decomposition
Analysis.
AB - OBJECTIVE: Chile, a South American country recently defined as a high-income
nation, carried out a major healthcare system reform from 2005 onwards that aimed
at reducing socioeconomic inequality in health. This study aimed to estimate
income-related inequality in self-reported health status (SRHS) in 2000 and 2013,
before and after the reform, for the entire adult Chilean population. METHODS:
Using data on equivalized household income and adult SRHS from the 2000 and 2013
CASEN surveys (independent samples of 101 046 and 172 330 adult participants,
respectively) we estimated Erreygers concentration indices (CIs) for above
average SRHS for both years. We also decomposed the contribution of both
"legitimate" standardizing variables (age and sex) and "illegitimate" variables
(income, education, occupation, ethnicity, urban/rural, marital status, number of
people living in the household, and healthcare entitlement). RESULTS: There was a
significant concentration of above average SRHS favoring richer people in Chile
in both years, which was less pronounced in 2013 than 2000 (Erreygers corrected
CI 0.165 [Standard Error, SE 0.007] in 2000 and 0.047 [SE 0.008] in 2013). To
help interpret the magnitude of this decline, adults in the richest fifth of
households were 33% more likely than those in the poorest fifth to report above
average health in 2000, falling to 11% in 2013. In 2013, the contribution of
illegitimate factors to income-related inequality in SRHS remained higher than
the contribution of legitimate factors. CONCLUSIONS: Income-related inequality in
SRHS in Chile has fallen after the equity-based healthcare reform. Further
research is needed to ascertain how far this fall in health inequality can be
attributed to the 2005 healthcare reform as opposed to economic growth and other
determinants of health that changed during the period.
PMID- 26418355
TI - Different Severity and Severity Predictors in Early-Onset and Late-Onset Asthma:
A Taiwanese Population-Based Study.
AB - BACKGROUND: Late-onset asthma has been shown to be more severe than early-onset
asthma in clinic-based studies. However, population-based studies are scarce, and
the predictors of severity have been less studied. OBJECTIVES: To determine
asthma severity and severity predictors regarding age at onset. METHODS: A cross
sectional questionnaire survey was conducted among parents of children from 94
schools in Taiwan in 2004. Asthma severity was defined as short-acting beta2
agonist (SABA), inhaled corticosteroid (ICS) and health care use in the last
year. Information on age at onset, demographics, heredity and home exposure was
collected. Ordered logistic or logistic regression was used for determining the
associations between risk factors and severity. RESULTS: Participants aged 26-50
years were included, resulting in 21,057 (67.8%) participants. Among them, 449
reported ever having had physician-diagnosed asthma, and 381 of those subjects
answered the question on age at asthma onset. The risks of rescue SABA, ICS and
health care use were generally higher among late-onset (13-50 years) than early
onset (0-12 years) asthmatics. Use of SABA and health care increased from
childhood-onset, adolescent- or young adult-onset to adult-onset asthma. Allergic
rhinitis was positively associated with SABA use (OR, 9.08; 95% CI, 1.06-77.99)
and ICS use (OR, 5.08; 95% CI, 1.47-17.52) in early-onset asthma. Dehumidifier
use was negatively associated with SABA use (OR, 0.50; 95% CI, 0.29-0.87) and ICS
use (OR, 0.38; 95% CI, 0.19-0.78) in late-onset asthma. CONCLUSIONS: In adults,
late-onset asthma was more severe than early-onset asthma. Severity, as indicated
by SABA and ICS use, was positively associated with allergic rhinitis in early
onset asthma and negatively associated with dehumidifier use in late-onset
asthma.
PMID- 26418356
TI - The European antibody network's practical guide to finding and validating
suitable antibodies for research.
AB - Antibodies are widely exploited as research/diagnostic tools and therapeutics.
Despite providing exciting research opportunities, the multitude of available
antibodies also offers a bewildering array of choice. Importantly, not all
companies comply with the highest standards, and thus many reagents fail basic
validation tests. The responsibility for antibodies being fit for purpose rests,
surprisingly, with their user. This paper condenses the extensive experience of
the European Monoclonal Antibody Network to help researchers identify antibodies
specific for their target antigen. A stepwise strategy is provided for
prioritising antibodies and making informed decisions regarding further essential
validation requirements. Web-based antibody validation guides provide practical
approaches for testing antibody activity and specificity. We aim to enable
researchers with little or no prior experience of antibody characterization to
understand how to determine the suitability of their antibody for its intended
purpose, enabling both time and cost effective generation of high quality
antibody-based data fit for publication.
PMID- 26418357
TI - A Longitudinal Study of Post-Traumatic Growth and Psychological Distress in
Colorectal Cancer Survivors.
AB - The stability of post-traumatic growth over time and the relationship between
post-traumatic growth and traditional distress outcomes remains unclear. We
tracked post-traumatic growth in a population-based sample of colorectal cancer
patients from soon after diagnosis to five years subsequently to assess the
heterogeneity of a post-traumatic growth response to cancer over time and
describe the simultaneous and longitudinal relationships between post-traumatic
growth and psychological distress. 1966 colorectal patients who were five months
post diagnosis were assessed six times over a five year period. There was
considerable heterogeneity associated with both psychological distress and
benefit finding scores over time. However, both for benefit finding and
psychological distress, the variation in individual scores suggested an
underlying positive linear trend and both lagged and lagged change components.
Specifically, benefit finding and psychological distress are mutual leading
indicators of each other. First, benefit finding served as a leading indicator of
distress, in that increases in reported benefit finding from year to year
predicted higher future increases in psychological distress. As well, in an
inverse relationship, psychological distress served as a leading indicator of
benefit finding, such that increases in reported distress from year to year
predicted lower future increases in benefit finding. Post-traumatic growth may
reflect patients coping efforts to enhance perceptions of wellbeing in response
to escalating cancer-related threats, acting as harbinger of increasing
trajectories of psychological distress. This explanation is consistent with a
cognitive dissonance response in which threats to the integrity of the self then
lead to a tendency to accentuate positive aspects of the self.
PMID- 26418358
TI - Time to Onset of Sustained Postoperative Pain Relief (SuPPR): Evaluation of a New
Systems-Level Metric for Acute Pain Management.
PMID- 26418359
TI - Perceptual Inference in Chronic Pain: An Investigation Into the Economy of Action
Hypothesis.
AB - OBJECTIVE: The experience of chronic pain critically alters one's ability to
interact with their environment. One fundamental issue that has received little
attention, however, is whether chronic pain disrupts how one perceives their
environment in the first place. The Economy of Action hypothesis purports that
the environment is spatially scaled according to the ability of the observer.
Under this hypothesis it has been proposed that the perception of the world is
different between those with and without chronic pain. Such a possibility has
profound implications for the investigation and treatment of pain. The present
investigation tested the application of this hypothesis to a heterogenous chronic
pain population. METHODS: Individuals with chronic pain (36; 27F) and matched
pain-free controls were recruited. Each participant was required to judge the
distance to a series of target cones, to which they were to subsequently walk. In
addition, at each distance, participants used Numerical Rating Scales to indicate
their perceived effort and perceived pain associated with the distance presented.
RESULTS: Our findings do not support the Economy of Action hypothesis: there were
no significant differences in distance estimates between the chronic pain and
pain-free groups (F1,60=0.927; P=0.340). In addition, we found no predictive
relationship in the chronic pain group between anticipated pain and estimated
distance (F1,154=0.122, P=0.727), nor anticipated effort (1.171, P=0.281) and
estimated distance (F1,154=1.171, P=0.281). DISCUSSION: The application of the
Economy of Action hypothesis and the notion of spatial perceptual scaling as a
means to assess and treat the experience of chronic pain are not supported by the
results of this study.
PMID- 26418360
TI - The Dutch Central Sensitization Inventory (CSI): Factor Analysis, Discriminative
Power, and Test-Retest Reliability.
AB - OBJECTIVES: A standardized assessment of central sensitization can be performed
with the Central Sensitization Inventory (CSI), an English questionnaire
consisting of 25 items relating to current health symptoms. The aim of this study
was to translate the CSI into Dutch, to perform a factor analysis to reveal the
underlying structure, examine its discriminative power, and test-retest
reliability. METHODS: The CSI was first translated into Dutch. A factor analysis
was conducted on CSI data of a large group of chronic pain patients (n=368). The
ability to discriminate between chronic pain patients (n=188) and pain-free
controls (n=49) was determined and the test-retest reliability for chronic pain
patients (n=36) and controls (n=45) with a time interval of 3 weeks was
evaluated. RESULTS: The exploratory factor analysis resulted in a 4-factor model
based on 20 items, representing the domains "General disability and physical
symptoms" (Cronbach alpha=0.80), "Higher central sensitivity"(Cronbach
alpha=0.78), "Urological and dermatological symptoms"(Cronbach alpha=0.60), and
"Emotional distress"(Cronbach alpha=0.80). Furthermore, a parsimonious second
order factor model was found, where the factor "General central sensitization"
was underlying the 4 first-order factors. Chronic pain patients scored
significantly worse on all 4 factors. The test-retest reliability was excellent
values in both chronic pain patients (ICC=0.88) and controls (ICC=0.91).
DISCUSSION: The original CSI was translated into Dutch and did not reveal any
problems during data acquisition. The domains represented by the 4 factors may be
useful in setting up specific patient profiles and treatment targets. To
conclude, the Dutch CSI revealed 4 distinguishable domains, showed good internal
consistency for the total score and 3 out of 4 domains, good discriminative
power, and excellent test-retest reliability.
PMID- 26418361
TI - TGFbeta Pathway Inhibition Redifferentiates Human Pancreatic Islet beta Cells
Expanded In Vitro.
AB - In-vitro expansion of insulin-producing cells from adult human pancreatic islets
could provide an abundant cell source for diabetes therapy. However,
proliferation of beta-cell-derived (BCD) cells is associated with loss of
phenotype and epithelial-mesenchymal transition (EMT). Nevertheless, BCD cells
maintain open chromatin structure at beta-cell genes, suggesting that they could
be readily redifferentiated. The transforming growth factor beta (TGFbeta)
pathway has been implicated in EMT in a range of cell types. Here we show that
human islet cell expansion in vitro involves upregulation of the TGFbeta pathway.
Blocking TGFbeta pathway activation using short hairpin RNA (shRNA) against
TGFbeta Receptor 1 (TGFBR1, ALK5) transcripts inhibits BCD cell proliferation and
dedifferentiation. Treatment of expanded BCD cells with ALK5 shRNA results in
their redifferentiation, as judged by expression of beta-cell genes and decreased
cell proliferation. These effects, which are reproducible in cells from multiple
human donors, are mediated, at least in part, by AKT-FOXO1 signaling. ALK5
inhibition synergizes with a soluble factor cocktail to promote BCD cell
redifferentiation. The combined treatment may offer a therapeutically applicable
way for generating an abundant source of functional insulin-producing cells
following ex-vivo expansion.
PMID- 26418363
TI - Highly efficient exciton harvesting and charge transport in ternary blend solar
cells based on wide- and low-bandgap polymers.
AB - We have designed highly efficient ternary blend solar cells based on a wide
bandgap crystalline polymer, poly(3-hexylthiophene) (P3HT), and a low-bandgap
polymer, poly[(4,4'-bis(2-ethylhexyl)dithieno[3,2-b:2'3'-d]silole)-2,6-diyl-alt
(2,1,3-benzothiadiazole)-4,7-diyl] (PSBTBT), and a fullerene derivative (PCBM).
By using highly crystalline P3HT, high fill factors were obtained even for
ternary blend solar cells, suggesting efficient charge transport due to large
P3HT crystalline domains. In such large crystalline domains, some P3HT excitons
could not diffuse into the interface with PCBM but can be collected in PSBTBT
domains by efficient energy transfer because of large spectral overlap between
the P3HT fluorescence and the PSBTBT absorption. Consequently, all the P3HT
excitons can contribute to the photocurrent generation at the P3HT/PCBM interface
and/or PSBTBT domains mixed with PCBM in the ternary blends. As a result,
P3HT/PSBTBT/PCBM ternary blend solar cells exhibit a power conversion efficiency
of 5.6%, which is even higher than those of both individual binary devices of
P3HT/PCBM and PSBTBT/PCBM.
PMID- 26418362
TI - Acute-Onset Tinnitus Is Associated with Contralateral Hearing in Sudden Deafness.
AB - OBJECTIVE: We aimed to evaluate the prognostic factors for acute-onset tinnitus
associated with unilateral idiopathic sudden sensorineural hearing loss (ISSNHL)
and to assess the relationship between these factors and the final recovery.
METHODS: A total of 770 patients with unilateral ISSNHL were enrolled
retrospectively and their medical records reviewed. Patients were classified into
two groups according to the presence of acute-onset tinnitus at the initial
examination. Patient characteristics and the results of pure-tone audiometry were
compared between the two groups initially and 3 months later. RESULTS: A total of
70.9% (n = 546) of patients had tinnitus initially. There was no significant
difference in the mean hearing thresholds of the affected ear irrespective of
accompanying tinnitus. In contrast, patients with tinnitus in the affected ear
tended to have significantly better mean hearing thresholds in the nonaffected
ear (p < 0.05). The logistic regression analysis revealed that better mean
hearing thresholds in the nonaffected ear were associated with tinnitus
occurrence (p < 0.05). Better hearing thresholds in the nonaffected ear, younger
age, absence of dizziness, low-tone hearing loss, and combined intratympanic
dexamethasone injection were associated with full recovery (p < 0.05). However,
tinnitus was not an independent risk factor for full recovery. CONCLUSION: Better
contralateral hearing was associated with both an increased incidence of
concurrent tinnitus and a better final recovery. However, tinnitus was not
related to full recovery.
PMID- 26418364
TI - Charge Blinking Statistics of Semiconductor Nanocrystals Revealed by Carbon
Nanotube Single Charge Sensors.
AB - We demonstrate the relation between the optical blinking of colloidal
semiconductor nanocrystals (NCs) and their electrical charge blinking for which
we provide the first experimental observation of power-law statistics. To show
this, we harness the performance of CdSe/ZnS NCs coupled with carbon nanotube
field-effect transistors (CNTFETs), which act as single charge-sensitive
electrometers with submillisecond time resolution, at room temperature. A random
telegraph signal (RTS) associated with the NC single-trap charging is observed
and exhibits power-law temporal statistics (tau(-alpha), with alpha in the range
of ~1-3), and a Lorentzian current noise power spectrum with a well-defined
1/f(2) corner. The spectroscopic analysis of the NC-CNTFET devices is consistent
with the charging of NC defect states with a charging energy of Ec >= 200 meV.
These results pave the way for a deeper understanding of the physics and
technology of nanocrystal-based optoelectronic devices.
PMID- 26418366
TI - Evaluation of beam delivery and ripple filter design for non-isocentric proton
and carbon ion therapy.
AB - This study aims at selecting and evaluating a ripple filter design compatible
with non-isocentric proton and carbon ion scanning beam treatment delivery for a
compact nozzle. The use of non-isocentric treatments when the patient is shifted
as close as possible towards the nozzle exit allows for a reduction in the air
gap and thus an improvement in the quality of scanning proton beam treatment
delivery. Reducing the air gap is less important for scanning carbon ions, but
ripple filters are still necessary for scanning carbon ion beams to reduce the
number of energy steps required to deliver homogeneous SOBP. The proper selection
of ripple filters also allows a reduction in the possible transverse and depth
dose inhomogeneities that could appear in non-isocentric conditions in
particular. A thorough review of existing ripple filter designs over the past 16
years is performed and a design for non-isocentric treatment delivery is
presented. A unique ripple filter quality index (QIRiFi) independent of the
particle type and energy and representative of the ratio between energy
modulation and induced scattering is proposed. The Bragg peak width evaluated at
the 80% dose level (BPW80) is proposed to relate the energy modulation of the
delivered Bragg peaks and the energy layer step size allowing the production of
homogeneous SOBP. Gate/Geant4 Monte Carlo simulations have been validated for
carbon ion and ripple filter simulations based on measurements performed at CNAO
and subsequently used for a detailed analysis of the proposed ripple filter
design. A combination of two ripple filters in a series has been validated for
non-isocentric delivery and did not show significant transverse and depth-dose
inhomogeneities. Non-isocentric conditions allow a significant reduction in the
spot size at the patient entrance (up to 350% and 200% for protons and carbon
ions with range shifter, respectively), and therefore in the lateral penumbra in
the patients.
PMID- 26418367
TI - Hepatic Arterial Phase in Gadoxetic Acid-Enhanced Liver Magnetic Resonance
Imaging: Analysis of Respiratory Patterns and Their Effect on Image Quality.
AB - OBJECTIVE: The aims of this study were to objectively evaluate patient
respiration and breathing change after contrast injection and to assess its
potential impact on image quality for the hepatic arterial phase in gadoxetic
acid-enhanced magnetic resonance imaging. MATERIALS AND METHODS: This
retrospective study was approved by the institutional review board, and the
requirement for informed consent was waived. One hundred fifty-four patients
underwent gadoxetic acid-enhanced liver magnetic resonance imaging with a 13
second breath-hold hepatic arterial phase. During the acquisition of precontrast
and hepatic arterial phases, the respiratory motion signal was acquired and
graded on a 4-point scale based on the SD of the respiratory waveform, with the
highest grade indicating the worst breath-hold. Breath-holding grades 3 and 4 for
the hepatic arterial phases were considered as breath-holding difficulty during
the hepatic arterial phase. Gadoxetic acid-related dyspnea was defined as when
the SD value of respiratory waveform during the hepatic arterial phase was 200
greater than that of the precontrast image. Then, the precontrast and hepatic
arterial phase images were evaluated with respect to overall image quality and
motion artifact using a 5-point scale, with the highest score indicating the
worst image quality. In the hepatic arterial phase, the correlation between
breath-holding degree and image quality parameters was evaluated using Pearson
correlation. The differences in mean image quality scores between patients with
and without gadoxetic acid-related dyspnea were evaluated using Student t test.
RESULTS: Based on the analysis of the respiratory waveforms, the incidence of
breath-holding difficulty during the hepatic arterial phase was 23.4% (33/154),
and the incidence of gadoxetic acid-related dyspnea was 6.5% (10/154). By image
analysis, the incidence of a degraded hepatic arterial phase (overall image
quality score >=4) was 5.2% (8/154). During the hepatic arterial phase, the
breath-holding degree correlated with overall image quality and motion artifacts
(r = 0.564 and 0.578, respectively). Patients with gadoxetic acid-related dyspnea
showed significantly worse image qualities of the hepatic arterial phase than
patients without gadoxetic acid-related dyspnea (all, P < 0.001), although image
qualities for the precontrast image were not statistically significant between
the 2 groups (all, P > 0.05). CONCLUSIONS: The objective analysis of respiratory
patterns during a breath-hold is feasible and useful for evaluating gadoxetic
acid-related dyspnea and its effect on image quality analysis.
PMID- 26418368
TI - Changes in Maximal Strength, Velocity, and Power After 8 Weeks of Training With
Pneumatic or Free Weight Resistance.
AB - Because free weight (FW) and pneumatic (PN) resistance are characterized by
different inertial properties, training with either resistance could afford
unique strength, velocity, and power adaptations. Eighteen resistance-trained men
completed baseline tests to determine their FW and PN bench press 1 repetition
maximum (1RM). During the FW session, 4 explosive repetitions were performed at
loads of 15, 30, 45, 60, 75, and 90% 1RM to assess force, velocity, and power.
Participants were then assigned to a FW or PN training group, which involved
three 90-minute sessions per week for 8 weeks. Both intervention groups completed
identical periodized programs with the exception of the resistance used to
perform all bench press movements. Free weight participants significantly
increased their FW and PN 1RM (10.4 and 9.4%), and maximum (any load) force
(9.8%), velocity (11.6%), and power (22.5%). Pneumatic-trained participants also
exhibited increases in FW and PN 1RM (11.6 and 17.5%), and maximum force (8.4%),
velocity (13.6%), and power (33.4%). Both interventions improved peak barbell
velocity at loads of 15 and 30% 1RM; however, only the PN-trained individuals
displayed improvements in peak force and power at these same loads. Training with
PN resistance may offer advantages if attempting to improve power at lighter
relative loads by affording an opportunity to consistently achieve higher
accelerations and velocities (F = ma), in comparison with FW. Exploiting the
inertial properties of the resistance, whether mass, elastic or PN, could afford
an opportunity to develop mixed-method training strategies and/or elicit unique
neuromuscular adaptations to suit the specific needs of athletes from sports
characterized by varying demands.
PMID- 26418369
TI - Effects of 4 Weeks of High-Intensity Interval Training and beta-Hydroxy-beta
Methylbutyric Free Acid Supplementation on the Onset of Neuromuscular Fatigue.
AB - This study investigated the effects of high-intensity interval training (HIIT)
and beta-hydroxy-beta-methylbutyric free acid (HMB) supplementation on physical
working capacity at the onset of neuromuscular fatigue threshold (PWC(FT)).
Thirty-seven participants (22 men, 15 women; 22.8 +/- 3.4 years) completed an
incremental cycle ergometer test (graded exercise test [GXT]); electromyographic
amplitude from the right vastus lateralis was recorded. Assessments occurred
preceding (PRE) and after 4 weeks of supplementation (POST). Participants were
randomly assigned to control (C, n = 9), placebo (P, n = 14), or supplementation
(S, n = 14) groups. Both P and S completed 12 HIIT sessions, whereas C maintained
normal diet and activity patterns. The PWC(FT) (W) was determined using the
maximal perpendicular distance (D(MAX)) method. Electromyographic amplitude
(MUVrms) over time was used to generate a cubic regression. Onset of fatigue (TF)
was the x-value of the point on the regression that was at D(MAX) from a line
between the first and last data points. The PWC(FT) was estimated using TF and
GXT power-output increments. The 2-way analysis of variance (ANOVA) (group *
time) resulted in a significant interaction for PWC(FT) (F = 6.69, p = 0.004).
Post hoc analysis with 1-way ANOVA resulted in no difference in PWC(FT) among
groups at PRE (F = 0.87, p = 0.43); however, a difference in PWC(FT) was shown
for POST (F = 5.46, p = 0.009). Post hoc analysis among POST values revealed
significant differences between S and both P (p = 0.034) and C (p = 0.003). No
differences (p = 0.226) were noted between P and C. Paired samples t-tests
detected significant changes after HIIT for S (p < 0.001) and P (p = 0.016), but
no change in C (p = 0.473). High-intensity interval training increased PWC(FT),
but HMB with HIIT was more effective than HIIT alone. Furthermore, it seems that
adding HMB supplementation with HIIT in untrained men and women may further
improve endurance performance measures.
PMID- 26418365
TI - LncRNA-Hh Strengthen Cancer Stem Cells Generation in Twist-Positive Breast Cancer
via Activation of Hedgehog Signaling Pathway.
AB - Cancer stem cells (CSCs) are a subpopulation of neoplastic cells with self
renewal capacity and limitless proliferative potential as well as high invasion
and migration capacity. These cells are commonly associated with epithelial
mesenchymal transition (EMT), which is also critical for tumor metastasis. Recent
studies illustrate a direct link between EMT and stemness of cancer cells. Long
non-coding RNAs (lncRNAs) have emerged as important new players in the regulation
of multiple cellular processes in various diseases. To date, the role of lncRNAs
in EMT-associated CSC stemness acquisition and maintenance remains unclear. In
this study, we discovered that a set of lncRNAs were dysregulated in Twist
positive mammosphere cells using lncRNA microarray analysis. Multiple lncRNAs
associated canonical signaling pathways were identified via bioinformatics
analysis. Especially, the Shh-GLI1 pathway associated lncRNA-Hh,
transcriptionally regulated by Twist, directly targets GAS1 to stimulate the
activation of hedgehog signaling (Hh). The activated Hh increases GLI1
expression, and enhances the expression of SOX2 and OCT4 to play a regulatory
role in CSC maintenance. Thus, the mammosphere-formation efficiency (MFE) and the
self-renewal capacity in vitro, and oncogenicity in vivo in Twist-positive breast
cancer cells are elevated. lncRNA-Hh silence in Twist-positive breast cells
attenuates the activated Shh-GLI1 signaling and decreases the CSC-associated SOX
and OCT4 levels, thus reduces the MFE and tumorigenesis of transplanted tumor.
Our results reveal that lncRNAs function as an important regulator endowing Twist
induced EMT cells to gain the CSC-like stemness properties.
PMID- 26418370
TI - Kinematics and Kinetics of Squats, Drop Jumps and Imitation Jumps of Ski Jumpers.
AB - Squats, drop jumps, and imitation jumps are commonly used training exercises in
ski jumping to enhance maximum force, explosive force, and sport-specific skills.
The purpose of this study was to evaluate the kinetics and kinematics of training
exercises in ski jumping and to find objective parameters in training exercises
that most correlate with the competition performance of ski jumpers. To this end,
barbell squats, drop jumps, and imitation jumps were measured in a laboratory
environment for 10 elite ski jumpers. Force and motion data were captured, and
the influence of maximum vertical force, force difference, vertical take-off
velocity, knee moments, knee joint power, and a knee valgus/varus index was
evaluated and correlated with their season jump performance. The results indicate
that, especially for the imitation jumps, a good correlation exists between the
vertical take-off velocity and the personal jump performance on the hill (R =
0.718). Importantly, however, the more the athletes tended toward a valgus knee
alignment during the measured movements, the worse their performance (R = 0.729
imitation jumps; R = 0.685 squats). Although an evaluation of the athletes' lower
limb alignment during competitive jumping on the hill is still required, these
preliminary data suggest that performance training should additionally
concentrate on improving knee alignment to increase ski jumping performance.
PMID- 26418371
TI - New Aggregation-Induced Emitters: Tetraphenyldistyrylbenzenes.
AB - The synthesis of five novel distyrylbenzene (DSB) derivatives, featuring a
central tetraphenylbenzene core, is reported. The targets show aggregation
induced emission (AIE), which, however, is substituent-dependent. For the pure
hydrocarbon and derivatives that do not carry (+M) or (-M) substituents, classic
AIE behavior is observed, that is, the DSBs are non-fluorescent in solution, but
are highly fluorescent in cold matrices, upon aggregate formation in poor
solvents and in the solid, crystalline state. If aldehyde or dibutylamino groups
are attached in the para-position of the DSB unit, non-classic AIE-phores result.
These are fluorescent both in dilute solution as well as in the solid state.
Prolonged irradiation of the targets leads to benzotetraphene derivatives by a
double cyclization.
PMID- 26418372
TI - REMD Simulations Reveal the Dynamic Profile and Mechanism of Action of
Deleterious, Rescuing, and Stabilizing Perturbations to NBD1 from CFTR.
AB - Cystic Fibrosis (CF) is a lethal, genetic disease caused by mutations to the CFTR
chloride channel. The most common CF causing mutation is the deletion of F508
from the first Nucleotide Binding Domain (F508del-NBD1). This mutation leads to a
thermally unstable domain and a misfolded, nonfunctioning CFTR. Replica Exchange
MD simulations were used to simulate seven NBD1 constructs including wt and
F508del-NBD1 both alone and in the presence of known rescuing mutations as well
as F508del-NBD1 in complex with a known small (ligand) stabilizer. Analyzing the
resulting trajectories suggests that differences in the biochemical properties of
the constructs result from local and coupled differences in their dynamic
profiles. A comparative analysis of these profiles as well as of the resulting
trajectories reveals how the different perturbations exert their deleterious,
rescuing, and stabilizing effects on NBD1. These simulations may therefore be
useful for the design and mechanism-of-action analysis of new NBD1 stabilizers.
PMID- 26418373
TI - Form follows function or does it?
PMID- 26418374
TI - Deletion of FAST (Fas-activated serine/threonine phosphoprotein) ameliorates
immune complex arthritis in mice.
PMID- 26418375
TI - Research on Evidence-Based Practice.
PMID- 26418377
TI - Erratum.
PMID- 26418376
TI - Ionogels of Sugar Surfactant in Ethylammonium Nitrate: Phase Transition from
Closely Packed Bilayers to Right-Handed Twisted Ribbons.
AB - In the simplest ionic liquid, ethylammonium nitrate (EAN), ionogels with high
mechanical strength were prepared from a surfactant with a disaccharide polar
head. Phase structures from closely packed bilayers to right-handed twisted
ribbons were determined via freeze-fracture transmission electron microscopy (FF
TEM) observations. The phase transition mechanism was investigated deeply and
systematically. The temperature contributes to suitable tail chain conformations
of surfactant molecules for adapting to different self-assembled structures
including right-handed twisted ribbons and bilayers. Two different arrays were
revealed for different bilayers by the small-angle X-ray scattering (SAXS)
measurements. The rheological and tribological properties of the ionogels were
investigated. The better lubricating property and antiwear capability of the
ionogels compared to the EAN may be attributed to the structure characteristics
and the good thixotropic properties.
PMID- 26418378
TI - New Perspectives of the Pathophysiology and Management in Heart Failure.
PMID- 26418379
TI - Hereditary Renal Hypouricemia Type 1 and Autosomal Dominant Polycystic Kidney
Disease.
AB - BACKGROUND: Renal hypouricemia (RHUC) is a heterogeneous inherited disorder
characterized by impaired tubular uric acid (UA) transport with severe
complications, such as acute kidney injury. Type 1 is caused by a mutation in the
SLC22A12 gene (URAT1) and type 2 in the SLC2A9 gene (GLUT9). In this article, the
authors present a coexpression functional characterization of variants
responsible for RHUC type 1 in a Czech family with polycystic kidney disease
(PKD). METHODS: The serum UA concentration in the proband was 1.1 mg/dL and was
expressed as an increase in the fractional excretion of UA (43%). The URAT1
allelic variants were prepared and their urate uptake and subcellular
localization were studied by Xenopus oocytes expression system. Linkage analysis
using a panel of 4 CA-repeat flanking markers for chromosome 16 and a panel of 3
CA-repeat flanking markers for chromosome 4 was performed, which carry the PKD1
and PKD2 genes, respectively. RESULTS: Coexpression results showed that p.G366R
and p.R477H suppressed urate transport by wild types. Colocalization studies
showed an accumulation of URAT1 in the endoplasmic reticulum of the p.G366R
variant and mainly retention of wild-type protein by variants p.G366R and
p.R477H. CONCLUSIONS: The findings suggest that not only loss-of-function
mutation of URAT1 but also the dominant-negative effect cause RHUC through loss
of UA absorption, partly due to protein misfolding caused by accumulation of
URAT1 protein in the endoplasmic reticulum.
PMID- 26418381
TI - Association Between Body Composition and Bone Mineral Density in Men on
Hemodialysis.
AB - Studies have revealed complex interactions between bone and fat, however there
are few studies about this crosstalk in patients with chronic kidney disease.
This study investigated possible relationship between bone mineral density (BMD)
and body composition in patients who underwent hemodialysis. Twenty patients were
enrolled in a cross-sectional study (47.0 [42.3-56.8] years, body mass index 26.0
+/- 4.2 kg/m, dialysis vintage of 48.5 [26.7-95.7] months). Body composition and
BMD were assessed by dual-energy X-ray absorptiometry. Leptin and parathormone
levels were analyzed using Multiplex kits (R&D System Inc). Low bone mass in the
femoral neck was reported in 54.8% of patients. Total BMD and total T-score were
positively correlated with lean mass (r = 0.46, P = 0.04; r = 0.47, P = 0.04,
respectively), but not with leptin or body fat mass. In conclusion, lean body
mass is probably important to maintain bone health in male patients who underwent
hemodialysis.
PMID- 26418382
TI - Augmented Hebbian reweighting accounts for accuracy and induced bias in
perceptual learning with reverse feedback.
AB - Using an asymmetrical set of vernier stimuli (-15", -10", -5", +10", +15")
together with reverse feedback on the small subthreshold offset stimulus (-5")
induces response bias in performance (Aberg & Herzog, 2012; Herzog, Eward,
Hermens, & Fahle, 2006; Herzog & Fahle, 1999). These conditions are of interest
for testing models of perceptual learning because the world does not always
present balanced stimulus frequencies or accurate feedback. Here we provide a
comprehensive model for the complex set of asymmetric training results using the
augmented Hebbian reweighting model (Liu, Dosher, & Lu, 2014; Petrov, Dosher, &
Lu, 2005, 2006) and the multilocation integrated reweighting theory (Dosher,
Jeter, Liu, & Lu, 2013). The augmented Hebbian learning algorithm incorporates
trial-by-trial feedback, when present, as another input to the decision unit and
uses the observer's internal response to update the weights otherwise; block
feedback alters the weights on bias correction (Liu et al., 2014). Asymmetric
training with reversed feedback incorporates biases into the weights between
representation and decision. The model correctly predicts the basic induction
effect, its dependence on trial-by-trial feedback, and the specificity of bias to
stimulus orientation and spatial location, extending the range of augmented
Hebbian reweighting accounts of perceptual learning.
PMID- 26418380
TI - Exposure to High-Risk Medications is Associated With Worse Outcomes in Older
Veterans With Chronic Pain.
AB - BACKGROUND: Chronic pain is common, costly and leads to significant morbidity in
older adults, yet there are limited data on medication safety. The authors sought
to evaluate the association of incident high-risk medication in the elderly
(HRME) with mortality, emergency department (ED) or hospital care among older
adults with chronic pain. METHODS: A retrospective Veterans Health Administration
cohort study was conducted examining older veterans with chronic pain diagnoses
and use of incident HRME (opioids, skeletal muscle relaxants, antihistamines and
psychotropics). Outcomes evaluated included all-cause mortality, ED visits or
inpatient hospital care. Descriptive statistics summarized variables for the
overall cohort, the chronic pain cohort and those with and without HRME. Separate
generalized linear mixed-effect regression models were used to examine the
association of incident HRME on each outcome, controlling for potential
confounders. RESULTS: Among 1,807,404 veterans who received Department of
Veterans Affairs care in 2005 to 2006, 584,066 (32.3%) had chronic pain; 45,945
veterans with chronic pain (7.9%) had incident HRME exposure. The strongest
significant associations of incident HRME were for high-risk opioids with all
cause hospitalizations (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.95
2.23), skeletal muscle relaxants with all-cause ED visits (OR 2.62, 95% CI 2.52
2.73) and mortality (OR 0.80, 95% CI 0.74-0.86), antihistamines with all-cause ED
visits (OR 2.82 95% CI 2.72-2.95) and psychotropics with all-cause
hospitalizations (OR 2.15, 95% CI 1.96-2.35). CONCLUSIONS: Our data indicate that
incident HRME is associated with clinically important adverse outcomes in older
veterans with chronic pain and highlight the importance of being judicious with
prescribing certain classes of drugs in this vulnerable population.
PMID- 26418383
TI - [The ENGAGE AF-TIMI 48 study].
PMID- 26418384
TI - [The PROMISE study].
PMID- 26418385
TI - [What meta-analyses teach us: pros and cons].
AB - The exponential increase in publications focusing on important clinical issues
represents a major challenge for patients, physicians, and decision-makers,
despite the braggadocio of many experts. Meta-analysis, when conducted within the
context of a systematic review, offers an efficient and potent tool to summarize
the clinical evidence accrued on a specific clinical question. Despite their many
strengths, which include statistical precision, external validity, and the
opportunity to analyze subgroups and moderators, meta-analyses also have many
limitations. In addition, they are criticized because potentially an exercise in
"mega-silliness", mixing "apples and oranges", unable to improve the quality of
primary studies (in keeping with the say "garbage in-garbage out"), and focusing
on an "average patient" who is only hypothetical. Yet, it is evident that meta
analyses will continue to play a key role in informing decision making whenever
the best approach is not self-evident. Thus, it is mandatory to know their main
features in order to use them critically and constructively, without being
dominated nor scared.
PMID- 26418386
TI - [About paroxysmal atrial fibrillation and difficulties in clinical practice.
Dubito ergo sum].
AB - The differences in terms of cardioembolic risk of permanent and paroxysmal atrial
fibrillation are reviewed. On the basis of the available literature, the authors
suggest that their equivalence reported in the recent guideline for the
management of patients with atrial fibrillation represents an oversimplification.
PMID- 26418387
TI - [Cardiovascular risk in polycystic kidney disease].
AB - Hypertension is common and occurs in the majority of autosomal dominant
polycystic kidney disease (ADPKD) patients prior to loss of kidney function.
Hypertension relates to progressive kidney enlargement, and is a significant
independent risk factor for progression to end-stage renal disease. The
pathogenesis of hypertension in ADPKD is complex and depends on many factors that
influence each other. High expression of PKD1 and PKD2 genes is present in the
cilia of tubular epithelial cells, in endothelial cells and in vascular smooth
muscle cells. Decreased or absent polycystin-1 or -2 expression is associated
with abnormal vascular structure and function. PKD1/PKD2 deficiency results in
reduced nitric oxide levels, altered endothelial response to shear stress with
attenuation in vascular relaxation. Activation of the renin-angiotensin
aldosterone system occurs in ADPKD due to decreased nitric oxide production as
well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst
size, further activation of the renin-angiotensin-aldosterone system occurs,
blood pressure increases and a vicious cycle ensues with enhanced cyst growth and
hypertension ultimately leading to end-stage renal disease. Inhibition of the
angiotensin-aldosterone system is possible with angiotensin-converting enzyme
inhibitors and seems to be the first-line treatment for hypertension in these
subjects. As suggested by the HALT-PKD study, an aggressive blood pressure
control is safe and recommended and is associated with preservation of kidney
function and a reduction in total kidney volume over time. A collaborative
multidisciplinary approach between nephrologists and cardiologists is necessary
for the monitoring of kidney and heart complications.
PMID- 26418388
TI - [The heart-friendly diet].
AB - The importance of proper diet in primary and secondary cardiovascular prevention
is now quite clear: several recent studies, e.g. on fat and saturated fat intake,
on sodium, and on dietary cholesterol, are being discussed by the lay press and
by professionals. This paper reviews the most solid published evidence on diet
and cardiovascular risk, to provide clinicians (namely, cardiologists) with a
useful tool to be discussed with patients. Where evidence was strong enough, we
discussed the cardiovascular actions of specific nutrients and of dietary
patterns. Particular attention was paid to dietary fat, carbohydrates (in terms
of glycemic index), and functional, polyphenol-rich foods. Of note, we critically
review the available evidence in light of the Italian dietary patterns, to draw
practical conclusions applicable to this country.
PMID- 26418389
TI - [Cardiac involvement in Churg-Strauss syndrome].
AB - Churg-Strauss syndrome, recently renamed eosinophilic granulomatosis with
polyangiitis (EGPA), is a rare form of systemic vasculitis, characterized by
disseminated necrotizing vasculitis with extravascular granulomas occurring among
patients with asthma and tissue eosinophilia. EGPA is classified as a small and
medium-sized vessel vasculitis associated with antineutrophil cytoplasmic
antibodies (ANCA) and the hypereosinophilic syndrome. Typical clinical features
include asthma, sinusitis, transient pulmonary infiltrates and neuropathy. Blood
eosinophils are often >1500/ul or more than 10% on the differential leukocyte
count. Blood eosinophils should always be tested in unexplained cardiac
disorders, and may normalize even after low doses of corticosteroids. ANCA are
positive in 40-60% of cases, mainly anti-myeloperoxidase. Heart involvement
occurs in approximately 15-60% of EGPA patients, especially those who are ANCA
negative. Any cardiac structure can be involved, and patients present with
myocarditis, heart failure, pericarditis, arrhythmia, coronary arteritis,
valvulopathy, intracavitary cardiac thrombosis. Although cardiovascular
involvement is usually an early manifestation, it can also occur later in the
course of the disease. A significant proportion of patients with cardiac
involvement is asymptomatic. In the absence of symptoms and major ECG
abnormalities, cardiac involvement may be detected in nearly 40% of the patients.
All patients with EGPA should be studied not only with a detailed history of
cardiac symptoms and ECG, but also with echocardiography; if abnormalities are
detected, a cardiac magnetic resonance study should be performed. Coronary
angiography and endomyocardial biopsy should be reserved to selected cases. Heart
involvement carries a poor prognosis and causes 50% of the deaths of these
patients. It is often insidious and underestimated. Optimal therapy is therefore
important and based on high-dose corticosteroids plus immunosuppressive agents,
particularly cyclophosphamide in case of myocardial inflammation. Thus, early
diagnosis of cardiac involvement and subsequent therapy may prevent progression
of cardiac disease. At present, the role of troponin and brain natriuretic
peptide in monitoring and therapy remains unclear. Orthotopic heart
transplantation is feasible in case of severe disease, even if the experience is
limited in -EGPA, and optimal post-transplantation immunosuppressive strategy has
yet to be defined.
PMID- 26418390
TI - [Quality indicators for the assessment of ST-segment elevation acute myocardial
infarction (STEMI) networks. How hospital discharge records could be integrated
with Emergency medical services data: the Emilia-Romagna STEMI network
experience].
AB - BACKGROUND: The assessment of the regional network for ST-segment elevation acute
myocardial infarction (STEMI) is fundamental for quality assurance. Since 2011
all Italian Health Authorities, in addition to hospital discharge records (HDR),
must provide a standardized information flow (ERD) about emergency department
(ED) and emergency medical system (EMS) activities. The aim of this study was to
evaluate whether data integration of ERD with HDR may allow the development of
appropriate quality indicators. METHODS: Patients admitted to coronary care units
(CCU) for STEMI between January 1 to December 31, 2013, were identified from the
regional HDR database. All data were linked to those of the regional ERD
database. Four quality indicators were defined: 1) rates of EMS activation, 2)
rates of EMS direct transfer to the catheterization laboratory (Cath-lab), 3)
transfer rates from a Spoke to a Hub hospital with angioplasty facilities, and 4)
median time spent in ED. RESULTS: In 2013, 2793 patients with STEMI were admitted
to the CCU. Of these, 1684 patients (60%) activated EMS and were transported to
Spoke or Hub hospitals; 955 (57%) entered directly in CCU/Cath-lab; 677 were
transferred directly to a Hub hospital ED without being admitted to a Spoke
hospital. The median ED time in Hub hospital was 47 min (IQR 24-136) and in Spoke
hospital 53 min (IQR 30-131). CONCLUSIONS: The integration among administrative
data banks (i.e., HDR with ERD) allowed the assessment of the regional STEMI
network and the identification of potentially useful quality indicators. Their
easy availability should enable comparisons with local, national and
international standards, and may favor quality improvement.
PMID- 26418391
TI - [Acute results of left ventricular endocardial pacing for cardiac
resynchronization therapy obtained with a transapical approach].
AB - Although cardiac resynchronization therapy (CRT) is considered a milestone in the
treatment of patients affected with chronic congestive heart failure, reduced
left ventricular ejection fraction and enlarged QRS, up to 30% of patients can be
considered clinical non-responders to this treatment. In these patients,
optimization of atrioventricular and interventricular intervals could be of some
help, but results of trials are not univocal on the benefit of this procedure. In
the last years, left ventricular endocardial pacing for CRT has emerged as a
possible solution in non-responders. Several studies have demonstrated its
feasibility and safety, and some reports suggest its incremental efficacy in
comparison with traditional epicardial pacing, both obtained transvenously or
surgically. We describe the cases of two patients already implanted with a CRT
device who came to our attention for clinical non-responsiveness to CRT and who
have been successfully treated with the addition of a left endocardial lead. A
brief literature review on this topic is also reported.
PMID- 26418392
TI - [Sequential spontaneous coronary artery dissection in a female patient on oral
ephedrine].
AB - Spontaneous coronary artery dissection (SCAD) is an infrequent, but not rare,
cause of acute coronary syndrome. It mainly affects young women, often with few
or no traditional cardiovascular risk factors. In the case described, a 57-year
old woman experienced a first episode of SCAD involving a distal branch of the
circumflex coronary artery--treated conservatively--followed, after a few hours,
by a second episode of SCAD involving the left anterior descending coronary
artery, complicated by hemodynamic instability and treated with emergency
angioplasty. During the previous months, the patient was taking a slimming drug
containing ephedrine. Dual spontaneous coronary dissection of different type and
involving two different vessels, which occurred in the same patient within a few
hours, testifies the heterogeneity of the clinical picture of this syndrome and
of the therapeutic approach.
PMID- 26418393
TI - [Syncope: an untreated symptom with a lifesaving intervention].
AB - We report the case of a 61-year-old woman referred to our center for cardiac
evaluation after a syncope, with echocardiographic findings of a papillary
fibroelastoma on the edge of the non-coronary aortic cusp. The three-dimensional
transesophageal approach provided a unique understanding of the size and shape of
the mass and it favorably directed the surgeon towards treatment with
conservative surgery.
PMID- 26418394
TI - Silver-Mediated Oxidative Trifluoromethylation of Alcohols to Alkyl
Trifluoromethyl Ethers.
AB - The development of an efficient and practical method for the preparation of alkyl
trifluoromethyl ethers is urgently demanding. The silver-mediated oxidative O
trifluoromethylation of primary, secondary, and tertiary alcohols with TMSCF3
under mild reaction conditions is established to provide a novel approach to a
broad range of alkyl trifluoromethyl ethers. Further, this method is applied to
the late-stage O-trifluoromethylation of complex natural products and prescribed
pharmaceutical agents.
PMID- 26418395
TI - Organized Aggregation of Porphyrins in Lipid Bilayers for Third Harmonic
Generation Microscopy.
AB - Nonlinear optical microscopy has become a powerful tool for high-resolution
imaging of cellular and subcellular composition, morphology, and interactions
because of its high spatial resolution, deep penetration, and low photo-damage to
tissue. Developing specific harmonic probes is essential for exploiting nonlinear
microscopic imaging for biomedical applications. We report an organized aggregate
of porphyrins (OAP) that formed within lipidic nanoparticles showing fingerprint
spectroscopic properties, structure-associated second harmonic generation, and
superradiant third harmonic generation. The OAP facilitated harmonic microscopic
imaging of living cells with significantly enhanced contrast. The structure
dependent switch between harmonic (OAP-intact) and fluorescence (OAP-disrupted)
generation enabled real-time multi-modality imaging of the cellular fate of
nanoparticles. Robustly produced under various conditions and easily incorporated
into pre-formed lipid nanovesicles, OAP provides a biocompatible nanoplatform for
harmonic imaging.
PMID- 26418396
TI - Priming for novel object associations: Neural differences from object item
priming and equivalent forms of recognition.
AB - The neural substrates of associative and item priming and recognition were
investigated in a functional magnetic resonance imaging study over two separate
sessions. In the priming session, participants decided which object of a pair was
bigger during both study and test phases. In the recognition session,
participants saw different object pairs and performed the same size-judgement
task followed by an associative recognition memory task. Associative priming was
accompanied by reduced activity in the right middle occipital gyrus as well as in
bilateral hippocampus. Object item priming was accompanied by reduced activity in
extensive priming-related areas in the bilateral occipitotemporofrontal cortex,
as well as in the perirhinal cortex, but not in the hippocampus. Associative
recognition was characterized by activity increases in regions linked to
recollection, such as the hippocampus, posterior cingulate cortex, anterior
medial frontal gyrus and posterior parahippocampal cortex. Item object priming
and recognition recruited broadly overlapping regions (e.g., bilateral middle
occipital and prefrontal cortices, left fusiform gyrus), even though the BOLD
response was in opposite directions. These regions along with the precuneus,
where both item priming and recognition were accompanied by activation, have been
found to respond to object familiarity. The minimal structural overlap between
object associative priming and recollection-based associative recognition
suggests that they depend on largely different stimulus-related information and
that the different directions of the effects indicate distinct retrieval
mechanisms. In contrast, item priming and familiarity-based recognition seemed
mainly based on common memory information, although the extent of common
processing between priming and familiarity remains unclear. Further implications
of these findings are discussed.
PMID- 26418397
TI - Dishonest Academic Conduct: From the Perspective of the Utility Function.
AB - Dishonest academic conduct has aroused extensive attention in academic circles.
To explore how scholars make decisions according to the principle of maximal
utility, the author has constructed the general utility function based on the
expected utility theory. The concrete utility functions of different types of
scholars were deduced. They are as follows: risk neutral, risk averse, and risk
preference. Following this, the assignment method was adopted to analyze and
compare the scholars' utilities of academic conduct. It was concluded that
changing the values of risk costs, internal condemnation costs, academic
benefits, and the subjective estimation of penalties following dishonest academic
conduct can lead to changes in the utility of academic dishonesty. The results of
the current study suggest that within scientific research, measures to prevent
and govern dishonest academic conduct should be formulated according to the
various effects of the above four variables.
PMID- 26418398
TI - To jab, or not to jab.
PMID- 26418399
TI - Differentiating between red legs and cellulitis and reviewing treatment options.
AB - Red legs (RL) is a chronic inflammatory condition often misdiagnosed as
cellulitis. Antibiotic therapy is not required and does not resolve the symptoms.
The main causes of RL are chronic dermatological and venous disease, including
chronic oedema. Raising awareness of this condition among health professionals
could prevent misdiagnosis and unnecessary costly and potentially harmful
antibiotic therapy. The aim of this paper is to highlight the differential
diagnoses and management of red legs, and the author also includes an example
through a case history.
PMID- 26418400
TI - Reviewing the importance of the cold chain in the distribution of vaccines.
AB - Vaccination is an effective public health measure to prevent and control a number
of infectious diseases. However, since vaccines are biological products and are
sensitive to both heat and cold, they need to be maintained within a narrow range
of temperatures, often referred to as the 'cold-chain'. This range, which is
between +2 degrees C and +8 degrees C with a target +5 degrees C, does not allow
for refreezing or storage at room temperature. This paper discusses the
importance of the cold chain, what should be done both to maintain it, and the
actions to be taken, should a break be noted. It is important to note the product
information supplied with vaccines, which is taken from the summary of product
characteristics that forms part of the licensing requirements for each vaccine,
and which will state how it should be stored. Using a vaccine that has not been
stored according to these instructions constitutes off-label use, for which the
individual practitioner must take responsibility. It also emphasises the fragile
nature of many public health interventions, maintenance of which require constant
vigilance and close cooperation between many groups and individuals.
PMID- 26418401
TI - Caring for stoma patients with arthritis and mental incapacities.
AB - Mental incapacities in the form of dementia, Parkinson's disease, Huntington's
disease, and the physical incapacities of arthritis are difficult hurdles for an
older patient who has to undergo stoma surgery, irrespective of the stoma being
temporary or permanent. The loss of intellectual and physical function can cause
significant deterioration in the patient's ability to carry out day-to-day
activities and can also manifest itself in changes in social behaviour. Caring
for these patients in the community will require the nurse to adjust the
patient's care accordingly, and provide a holistic and more individualised care
package that includes the support of the carer or spouse. This article discusses
the ways in which community nurses can help the older stoma patient and carer.
PMID- 26418402
TI - Role of district and community nurses in bereavement care: a qualitative study.
AB - BACKGROUND: The district nurse is one of the main providers of palliative care,
which includes bereavement care. However, previous evidence shows a lack of
education and training, as well as time management, as important factors in the
delivery of bereavement care. AIM: This qualitative study aimed to explore the
provision of bereavement care from a district nurse's perspective. METHOD: Data
were collected from five participants using semi-structured interviews, and
thematically analysed to produce the findings. The interviews were conducted
within the author's and participants' working environments to maintain a
professional stance between both parties. FINDINGS: The results suggest an
awareness of bereavement care, but a lack of training and education into the
theoretical aspects of the care. Knowing the types and stages of bereavement
would be beneficial, both in the delivery and the identification of the most
effective time to refer on. CONCLUSION: Bereavement care was understood to be
part of the district nurse role, but the findings suggest that some nurses get
too involved and no end date could be standardised, as each case is dependent on
need. More experience of bereavement care and exposure increased awareness to its
importance and improved confidence toward its delivery.
PMID- 26418403
TI - Reviewing education challenges and solutions for health professionals in
community care.
AB - The biggest asset of the NHS is its staff. Health professionals working in the
community are faced with a number of challenges to maintain and develop their
knowledge and skills in their clinical practice. NHS England's Five Year Forward
View describes the need for change, identifying the necessity to reshape care
delivery, harnessing technology, and driving down variations in quality and
safety of care. This article explores some of the challenges faced by community
health-care providers and reviews possible solutions to meet community health
care needs for now as well as the future.
PMID- 26418405
TI - Facing death: 'in our unconscious, we are immortal'.
PMID- 26418404
TI - Understanding the Code: keeping accurate records.
AB - In his continuing series looking at the legal and professional implications of
the Nursing and Midwifery Council's revised Code of Conduct, Richard Griffith
discusses the elements of accurate record keeping under Standard 10 of the Code.
This article considers the importance of accurate record keeping for the safety
of patients and protection of district nurses. The legal implications of records
are explained along with how district nurses should write records to ensure these
legal requirements are met.
PMID- 26418406
TI - Providing meaningful support to patients with asthma.
PMID- 26418407
TI - Community nursing: the linchpin of quality care.
PMID- 26418408
TI - Validation of the Canada Acute Coronary Syndrome Risk Score for Hospital
Mortality in the Gulf Registry of Acute Coronary Events-2.
AB - BACKGROUND: Several risk scores have been developed for acute coronary syndrome
(ACS) patients, but their use is limited by their complexity. The new Canada
Acute Coronary Syndrome (C-ACS) risk score is a simple risk-assessment tool for
ACS patients. This study assessed the performance of the C-ACS risk score in
predicting hospital mortality in a contemporary Middle Eastern ACS cohort.
HYPOTHESIS: The C-ACS score accurately predicts hospital mortality in ACS
patients. METHODS: The baseline risk of 7929 patients from 6 Arab countries who
were enrolled in the Gulf RACE-2 registry was assessed using the C-ACS risk
score. The score ranged from 0 to 4, with 1 point assigned for the presence of
each of the following variables: age >=75 years, Killip class >1, systolic blood
pressure <100 mm Hg, and heart rate >100 bpm. The discriminative ability and
calibration of the score were assessed using C statistics and goodness-of-fit
tests, respectively. RESULTS: The C-ACS score demonstrated good predictive values
for hospital mortality in all ACS patients with a C statistic of 0.77 (95%
confidence interval [CI]: 0.74-0.80) and in ST-segment elevation myocardial
infarction and non-ST-segment elevation acute coronary syndrome patients (C
statistic: 0.76, 95% CI: 0.73-0.79; and C statistic: 0.80, 95% CI: 0.75-0.84,
respectively). The discriminative ability of the score was moderate regardless of
age category, nationality, and diabetic status. Overall, calibration was optimal
in all subgroups. CONCLUSIONS: The new C-ACS score performed well in predicting
hospital mortality in a contemporary ACS population outside North America.
PMID- 26418410
TI - Assessing Bleeding Risk With the HAS-BLED Score: Balancing Simplicity,
Practicality, and Predictive Value in Bleeding-Risk Assessment.
PMID- 26418409
TI - The HAS-BLED Score for Predicting Major Bleeding Risk in Anticoagulated Patients
With Atrial Fibrillation: A Systematic Review and Meta-analysis.
AB - Our objective was to compare the diagnostic accuracy between the HAS-BLED score
and any of HEMORR2 HAGES, ATRIA, CHADS2 , or CHA2 DS2 -VASc scores in
anticoagulated patients with atrial fibrillation. We systematically searched the
Cochrane Library, MEDLINE, PubMed, and Embase databases for relevant studies.
Data were extracted and analyzed according to predefined clinical endpoints.
Eleven studies were identified. Discrimination analysis demonstrates that HAS
BLED has no significant C-statistic differences for bleeding risk prediction
compared with ATRIA or HEMORR2 HAGES, but it has significant differences compared
with CHADS2 or CHA2 DS2 -VASc. The significant positive net reclassification
improvement and integrated discrimination improvement values also show that HAS
BLED is superior to that of any of HEMORR2 HAGES, ATRIA, CHADS2 , or CHA2 DS2
VASc scores. According to calibration analysis of HAS-BLED, it overpredicts the
risk of bleeding in the low (risk ratio [RR]: 1.16, 95% confidence interval [CI]:
0.63-2.13, P = 0.64) risk stratification but underpredicts that in the moderate
(RR: 0.66, 95% CI: 0.51-0.86, P = 0.002) and high (RR: 0.88, 95% CI: 0.70-1.10, P
= 0.27) risk stratifications. The HAS-BLED score not only performs better than
the HEMORR2 HAGES and ATRIA bleeding scores, but it also is superior to the
CHADS2 and CHA2 DS2 -VASc stroke scores for bleeding prediction. The HAS-BLED
score should be the optimal choice to assess major bleeding risk in clinical
practice.
PMID- 26418411
TI - Smart Muscle-Driven Self-Cleaning of Biomimetic Microstructures from Liquid
Crystal Elastomers.
AB - Muscle-driven actuation of biomimetic microfibrillar structures is achieved using
integrative soft-lithography on a backing splayed liquid-crystal elastomer (LCE).
Variation in the backing LCE layer thickness yields different modes of thermal
deformation from a pure bend to a twist-bend. Muscular motion and dynamic self
cleaning of gecko toe pads are mimicked via this mechanism.
PMID- 26418412
TI - Pharmacokinetics and Urinary Excretion Mechanism of Orteronel (TAK-700), A Novel
17,20-Lyase Inhibitor, in Animals.
AB - Orteronel is newly identified as a selective 17,20-lyase inhibitor for an agent
for castration resistant prostate cancer. The absorption and disposition of
[(14)C]orteronel were investigated in rats and monkeys. Orteronel was extensively
excreted into rat and monkey urine in an unchanged form after oral
administration. The unbound based renal clearances in rats and monkeys were
greater than the respective glomerular filtration rates (GFR), suggesting that
urinary tubular secretion plays an important role in the renal excretion of
orteronel. Therefore, the uptake of [(14)C]orteronel was investigated using rat
kidney slices to estimate the contribution of carrier-mediated transport on the
urinary tubular secretion. The uptake study using rat kidney slices suggested
that the transport of orteronel from the blood circulation to the kidney was
mediated by a digoxin sensitive transport system represented by Oatp4c1 and non
saturable components. Furthermore, the saturable component accounted for a
limited fraction of the total renal uptake by rat kidney slices. These results
suggested that non-saturable uptake mainly contributed to the renal excretion of
orteronel in rats.
PMID- 26418413
TI - Acotiamide Hydrochloride, a Therapeutic Agent for Functional Dyspepsia, Enhances
Acetylcholine-induced Contraction via Inhibition of Acetylcholinesterase Activity
in Circular Muscle Strips of Guinea Pig Stomach.
AB - Acotiamide is a first-in-class prokinetic drug approved in Japan for the
treatment of functional dyspepsia. Given that acotiamide enhances gastric
motility in conscious dogs and rats, we assessed the in vitro effects of this
drug on the contraction of guinea pig stomach strips and on acetylcholinesterase
(AChE) activity in stomach homogenate following fundus removal. We also
investigated the serotonin 5-HT4 receptor agonist mosapride, dopamine D2 receptor
and AChE inhibitor itopride, and representative AChE inhibitor neostigmine.
Acotiamide (0.3 and 1 MUM) and itopride (1 and 3 MUM) significantly enhanced the
contraction of gastric body strips induced by electrical field stimulation (EFS),
but mosapride (1 and 10 MUM) did not. Acotiamide and itopride significantly
enhanced the contraction of gastric body and antrum strips induced by
acetylcholine (ACh), but not that induced by carbachol (CCh). Neostigmine also
significantly enhanced the contraction of gastric body strips induced by ACh, but
not that by CCh. In contrast, mosapride failed to enhance contractions induced by
either ACh or CCh in gastric antrum strips. Acotiamide exerted mixed inhibition
of AChE, and the percentage inhibition of acotiamide (100 MUM) against AChE
activity was markedly reduced after the reaction mixture was dialyzed. In
contrast, itopride exerted noncompetitive inhibition on AChE activity. These
results indicate that acotiamide enhances ACh-dependent contraction in gastric
strips of guinea pigs via the inhibition of AChE activity, and that it exerts
mixed and reversible inhibition of AChE derived from guinea pig stomach.
PMID- 26418414
TI - Pharmacokinetic Study of a Diclofenac Sodium Capsule Filled with Enteric-coated
Pellets in Healthy Chinese Volunteers by Liquid Chromatography-electrospray
Ionization-tandem Mass Spectrometry.
AB - The pharmacokinetic study of a diclofenac sodium capsule filled with enteric
coated pellets (abbreviated as CAPSULE) in healthy Chinese subjects was evaluated
using liquid chromatography-electrospray ionization-tandem mass spectrometry with
simple sample preparation. In a cross-over study, 12 healthy male volunteers were
given 50 mg CAPSULE and diclofenac sodium enteric-coated tablet (abbreviated as
TABLET, used as a control dosage form) at fasting. The Cmax, AUC0-t, and Tmax of
CAPSULE were 1.01+/-0.52 MUg/mL, 1.54+/-0.18 MUg.h/mL, and 1.50+/-1.31 h,
respectively. When compared with TABLET, the pharmacokinetic study showed that
although this CAPSULE exhibited similar AUC (only 10% lower), it presented lower
maximum plasma concentration, faster absorption and shorter time to reach maximum
concentration. When compared with the previous study in Germany, obvious
variations on Tmax were found in Chinese subjects taking CAPSULE, but not TABLET.
The results indicated that individual difference should be paid attention when
prescribing CAPSULE to Chinese patients.
PMID- 26418415
TI - Relationship between Tregitopes Structure and Binding with Major
Histocompatibility Complex Class I.
AB - Epitopes of T-cells (tregitopes) are linear sequences of amino acids present in
many animal and human proteins. Tregitopes suppress the immunological response
and could play a significant regulatory role in the pathogenesis of autoimmune
diseases. They modulate T-cell response activated by the antigens of the major
histocompatibility complex class I (MHC-I).The aim of this study was an attempt
to determine the correlation between physicochemical properties and structures of
tregitopes and their binding strength with MHC-I. 21 amino acid sequences of
immunoglobulin G with verified or similar to tregitopes function were selected.
The analysis of the binding strength with MHC-I was carried out on 41 various
alleles since MHC-I can be coded by numerous alleles. The first phase of study
attempted to find a correlation between the half minimal inhibitory concentration
(LogIC50) calculated for MHC-I and physicochemical properties. From formulated
arithmetic statements, only one allowed to determine significant correlation with
LogIC50 with reference to alleles A*02:01 and A*02:06. The correlations for the
alleles were linear and sigmoid, respectively (p<0.001). The presence of the
repeated amino acids was confirmed in the sequences of the studied compounds.
These amino acids are connected with stronger binding or lack of the binding with
MHC-I expressed by LogIC50. The study shows the translation from the
classification (cloud) model to the linear one. The significant linear dependence
between chemical structure of tregitopes and their LogIC50 calculated for MHC-I
was displayed. The presented method can be used in screening of new sequences
that have regulatory properties for regulatory T-cells.
PMID- 26418416
TI - Correction: Analysis of Response Elements Involved in the Regulation of the Human
Neonatal Fc Receptor Gene (FCGRT).
PMID- 26418417
TI - CT segmentation of dental shapes by anatomy-driven reformation imaging and B
spline modelling.
AB - Dedicated imaging methods are among the most important tools of modern computer
aided medical applications. In the last few years, cone beam computed tomography
(CBCT) has gained popularity in digital dentistry for 3D imaging of jawbones and
teeth. However, the anatomy of a maxillofacial region complicates the assessment
of tooth geometry and anatomical location when using standard orthogonal views of
the CT data set. In particular, a tooth is defined by a sub-region, which cannot
be easily separated from surrounding tissues by only considering pixel grey
intensity values. For this reason, an image enhancement is usually necessary in
order to properly segment tooth geometries. In this paper, an anatomy-driven
methodology to reconstruct individual 3D tooth anatomies by processing CBCT data
is presented. The main concept is to generate a small set of multi-planar
reformation images along significant views for each target tooth, driven by the
individual anatomical geometry of a specific patient. The reformation images
greatly enhance the clearness of the target tooth contours. A set of meaningful
2D tooth contours is extracted and used to automatically model the overall 3D
tooth shape through a B-spline representation. The effectiveness of the
methodology has been verified by comparing some anatomy-driven reconstructions of
anterior and premolar teeth with those obtained by using standard tooth
segmentation tools. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26418418
TI - Correction: The Absence of CYP3A5*3 Is a Protective Factor to Anticonvulsants
Hypersensitivity Reactions: A Case-Control Study in Brazilian Subjects.
PMID- 26418419
TI - Comprehensive Identification of Sexual Dimorphism-Associated Differentially
Expressed Genes in Two-Way Factorial Designed RNA-Seq Data on Japanese Quail
(Coturnix coturnix japonica).
AB - Japanese quail (Coturnix coturnix japonica) reach sexual maturity earlier, breed
rapidly and successfully, and cost less and require less space than other birds
raised commercially. Given the value of this species for food production and
experimental use, more studies are necessary to determine chromosomal regions and
genes associated with gender and breed-differentiation. This study employed
Trinity and edgeR for transcriptome analysis of next-generation RNA-seq data,
which included 4 tissues obtained from 3 different breeding lines of Japanese
quail (random bred control, heavy weight, low weight). Differentially expressed
genes shared between female and male tissue contrast groups were analyzed to
identify genes related to sexual dimorphism as well as potential novel candidate
genes for molecular sexing. Several of the genes identified in the present study
as significant sex-related genes have been previously found in avian gene
expression analyses (NIPBL, UBAP2), and other genes found differentially
expressed in this study and not previously associated with sex-related
differences may be considered potential candidates for molecular sexing (TERA,
MYP0, PPR17, CASQ2). Additionally, other genes likely associated with neuronal
and brain development (CHKA, NYAP), as well as body development and size
differentiation (ANKRD26, GRP87) in quail were identified. Expression of homeobox
protein regulating genes (HXC4, ISL1) shared between our two sex-related contrast
groups (Female Brain vs. Male Brain and Ovary vs. Testis) indicates that these
genes may regulate sex-specific anatomical development. Results reveal genetic
features of the quail breed and could allow for more effective molecular sexing
as well as selective breeding for traits important in commercial production.
PMID- 26418421
TI - Extended Suspect and Non-Target Strategies to Characterize Emerging Polar Organic
Contaminants in Raw Wastewater with LC-HRMS/MS.
AB - An integrated workflow based on liquid chromatography coupled to a quadrupole
time-of-flight mass spectrometer (LC-QTOF-MS) was developed and applied to detect
and identify suspect and unknown contaminants in Greek wastewater. Tentative
identifications were initially based on mass accuracy, isotopic pattern,
plausibility of the chromatographic retention time and MS/MS spectral
interpretation (comparison with spectral libraries, in silico fragmentation).
Moreover, new specific strategies for the identification of metabolites were
applied to obtain extra confidence including the comparison of diurnal and/or
weekly concentration trends of the metabolite and parent compounds and the
complementary use of HILIC. Thirteen of 284 predicted and literature metabolites
of selected pharmaceuticals and nicotine were tentatively identified in influent
samples from Athens and seven were finally confirmed with reference standards.
Thirty four nontarget compounds were tentatively identified, four were also
confirmed. The sulfonated surfactant diglycol ether sulfate was identified along
with others in the homologous series (SO4C2H4(OC2H4)xOH), which have not been
previously reported in wastewater. As many surfactants were originally found as
nontargets, these compounds were studied in detail through retrospective
analysis.
PMID- 26418420
TI - Experimental Infection of Sheep at 45 and 60 Days of Gestation with Schmallenberg
Virus Readily Led to Placental Colonization without Causing Congenital
Malformations.
AB - BACKGROUND: Main impact of Schmallenberg virus (SBV) on livestock consists in
reproductive disorders, with teratogenic effects, abortions and stillbirths. SBV
pathogenesis and viral placental crossing remain currently poorly understood.
Therefore, we implemented an experimental infection of ewes, inoculated with SBV
at 45 or 60 days of gestation (dg). METHODOLOGY: "Mourerous" breed ewes were
randomly separated in three groups: eight and nine ewes were subcutaneously
inoculated with 1 ml of SBV infectious serum at 45 and 60 dg, respectively (G45
and G60). Six other ewes were inoculated subcutaneously with sterile phosphate
buffer saline as control group. All SBV inoculated ewes showed RNAemia consistent
with previously published studies, they seroconverted and no clinical sign was
reported. Lambs were born at term via caesarian-section, and right after birth
they were blood sampled and clinically examined. Then both lambs and ewes were
euthanatized and necropsied. PRINCIPAL FINDINGS/SIGNIFICANCE: No lambs showed any
malformation suggestive of SBV infection and none of them had RNAemia or anti-SBV
antibodies prior to colostrum uptake. Positive SBV RNA detection in organs was
rare in both G45 and G60 lambs (2/11 and 1/10, respectively). Nevertheless most
of the lambs in G45 (9/11) and G60 (9/10) had at least one extraembryonic
structure SBV positive by RTqPCR. The number of positive extraembryonic
structures was significantly higher in G60 lambs. Time of inoculation (45 or 60
dg) had no impact on the placental colonization success rate but affected the
frequency of detecting the virus in the offspring extraembryonic structures by
the time of lambing. SBV readily colonized the placenta when ewes were infected
at 45 or 60 dg but infection of the fetuses was limited and did not lead to
congenital malformations.
PMID- 26418422
TI - Toxicity of Tributyltin in Juvenile Common Carp (Cyprinus Carpio): Physiological
Responses, Hepatic Gene Expression, and Stress Protein Profiling.
AB - In this study, the effects of tributyltin (TBT) on biochemical parameters
(antioxidant responses and Na(+) -K(+) -ATPase) in different tissues were
investigated by using juvenile common carp (Cyprinus Carpio) as well as growth
and ion regulation-related genes expression and stress-related proteins profiling
in fish liver. Oxidative stress indices and Na(+) -K(+) -ATPase showed tissues
specific responses in fish exposed to different TBT concentrations. All tested
genes related to GH/IGF-I axis and ion-regulation were significantly induced in
the TBT group with lower concentrations (except for the igfbp3 in 10 MUg/L) and
were inhibited in 20 MUg/L. In addition, the profiling of two proteins Hsp 70 and
MT were increasing in a dose-dependent manner under TBT stress. In short, TBT
induced biochemical and molecular responses in different tissues were reflected
in the measured parameters in the test. On the basis of TBT residue levels in the
natural environment, more long-term experiments at lower concentrations will be
necessary in the future.
PMID- 26418424
TI - A Tribute to Martin D. Brasier: Palaeobiologist and Astrobiologist (April 12,
1947-December 16, 2014).
PMID- 26418425
TI - Is disulphide/thiol ratio related to blood pressure in masked hypertension?
AB - Dynamic thiol/disulphide homeostasis plays a critical role in numerous
intracellular enzymatic pathways including antioxidant defence and
detoxification. In this study, we sought to investigate dynamic thiol/disulphide
homeostasis in patients with masked hypertension (MHT) and its relationship with
blood pressure. Forty patients (23 men, 17 women) with newly diagnosed MHT and
not yet on medical therapy, and 40 healthy volunteers (21 men, 19 women) were
enrolled. Blood thiol/disulphide homeostasis was measured in both groups. Serum
native and total thiol levels were measured using the novel, fully automated
colorimetric method developed by Erel et al. Serum disulphide level was
calculated as (serum total thiol - serum native thiol)/2. Native and total thiol
levels (p = 0.001) and native thiol/total thiol ratio (p = 0.023) were found to
be lower in patients with MHT when compared to those of the control group.
Disulphide level and ratios of disulphide/native thiol and disulphide/total thiol
were higher in patients with MHT than in the control group (p = 0.001). A
positive correlation of systolic blood pressure (SBP) and diastolic blood
pressure (DBP) was observed with disulphide/native thiol ratio (p < 0.001).
Stepwise multivariable regression analysis showed disulphide/native thiol ratio
to be an independent risk factor of SBP and DBP, and SBP to be an independent
risk factor of disulphide/thiol ratio (p = 0.001). In this study, we found that
dynamic thiol/disulphide homeostasis shifted towards disulphide formation due to
thiol oxidation in patients with MHT. Prospective randomised controlled studies
are required to elucidate whether abnormal thiol/disulphide status lies in the
pathogenesis of MHT or is a consequence of MHT.
PMID- 26418423
TI - Lack of CD151/integrin alpha3beta1 complex is predictive of poor outcome in node
negative lobular breast carcinoma: opposing roles of CD151 in invasive lobular
and ductal breast cancers.
AB - BACKGROUND: The proposed involvement of CD151 in breast cancer (BCa) progression
is based on findings from studies in invasive ductal carcinoma (IDC). The IDC and
invasive lobular carcinoma (ILC) represent distinct disease entities. Here we
evaluated clinical significance of CD151 alone and in association with integrin
alpha3beta1 in patients with ILC in context of the data of our recent IDC study.
METHODS: Expression of CD151 and/or integrin alpha3beta1 was evaluated in ILC
samples (N=117) using immunohistochemistry. The findings were analysed in
relation to our results from an IDC cohort (N=182) demonstrating a prognostic
value of an expression of CD151/integrin alpha3beta1 complex in patients with
HER2-negative tumours. RESULTS: Unlike in the IDCs, neither CD151 nor
CD151/alpha3beta1 complex showed any correlation with any of the ILC
characteristics. Lack of both CD151 and alpha3beta1 was significantly correlated
with poor survival (P=0.034) in lymph node-negative ILC N(-) cases. The CD151(
)/alpha3beta1(-) patients had 3.12-fold higher risk of death from BCa in
comparison with the rest of the ILC N(-) patients. CONCLUSIONS: Biological role
of CD151/alpha3beta1 varies between ILC and IDC. Assessment of CD151/alpha3beta1
might help to identify ILC N(-) patients with increased risk of distant
metastases.
PMID- 26418426
TI - High genetic variation in resting-stage production in a metapopulation: Is there
evidence for local adaptation?
AB - Local adaptation is a key process for the maintenance of genetic diversity and
population diversification. A better understanding of the mechanisms that allow
(or prevent) local adaptation constitutes a key in apprehending how and at what
spatial scale it occurs. The production of resting stages is found in many taxa
and reflects an adaptation to outlast adverse environmental conditions. Daphnia
magna (Crustacea) can alternate between asexual and sexual reproduction, the
latter being linked to dormancy, as resting stages can only be produced sexually.
In this species, on a continental scale, resting-stage production is locally
adapted--that is, it is induced when the photoperiod indicates the imminence of
habitat deterioration. Here, we aimed to explore whether selection is strong
enough to maintain local adaptation at a scale of a few kilometers. We assessed
life-history traits of 64 D. magna clones originating from 11 populations of a
metapopulation with permanent and intermittent pool habitats. We found large
within- and between-population variation for all dormancy-related traits, but no
evidence for the hypothesized higher resting-stage production in animals from
intermittent habitats. We discuss how gene flow, founder events, or other forms
of selection might interfere with the process of local adaptation.
PMID- 26418428
TI - Does Sarcopenia Impact Complications and Overall Survival in Patients Undergoing
Radical Nephrectomy for Stage III and IV Kidney Cancer?
AB - PURPOSE: To investigate the association of sarcopenia (muscle mass wasting) with
complications and survival in patients undergoing radical nephrectomy for
advanced kidney cancer. PATIENTS AND METHODS: We identified 137 patients with
stage III and IV kidney cancer who underwent radical nephrectomy between 2008 and
2012. Preoperative cross-sectional imaging was used to measure total psoas area
(TPA) at the level of L3 and controlled for height (m(2)). Sarcopenia was
identified as TPA in the lowest gender-specific quartile. Patient characteristics
and postoperative complications were compared between sarcopenic and
nonsarcopenic patients. Kaplan-Meier survival curve estimates were generated for
overall and gender-specific survival. RESULTS: Preoperative cross-sectional
imaging was available for 128 patients (93%, 85 men and 43 women). Mean TPA for
men was 5.49 cm(2)/m(2) versus 4.27 cm(2)/m(2) for women (P < 0.05). Sarcopenia
was associated with risk of Clavien grade III or higher complication (P = 0.03)
and node-positive disease (P = 0.01). Median follow-up was 48.3 months. Kaplan
Meier estimates of overall and gender-specific survival were similar between
sarcopenic and nonsarcopenic patients. CONCLUSION: Sarcopenia appears to be
associated with risk of major complication after radical nephrectomy for advanced
kidney cancer. It was not related to overall survival, however. This preoperative
imaging tool may be helpful in preoperative counseling and preparation.
PMID- 26418429
TI - Full-Thickness Astigmatic Keratotomy Combined With Small-Incision Lenticule
Extraction to Treat High-Level and Mixed Astigmatism.
AB - PURPOSE: To explore the clinical effects of combined full-thickness astigmatic
keratotomy and small-incision lenticule extraction (SMILE) in patients who are
inoperable using SMILE alone. METHODS: We included 13 eyes of 9 patients with
high-level or mixed astigmatism who underwent full-thickness astigmatic
keratotomy followed by SMILE (secondarily) to correct the residual refractive
error. RESULTS: Six months after SMILE, the spherical equivalent was reduced from
-4.83 +/- 3.26 D to -0.17 +/- 0.38 D (P < 0.001), and the astigmatism was reduced
from 5.12 +/- 0.96 D to 0.21 +/- 0.22 D (P < 0.001). The uncorrected and
corrected (CDVA) distance visual acuities improved from 1.07 +/- 0.62 to 0.02 +/-
0.13 (P < 0.001) and from 0.08 +/- 0.14 to -0.01 +/- 0.14 (P = 0.002),
respectively. The CDVA improved by 1 or 2 Snellen lines in 8 cases (61.5%), and
there was no loss in CDVA. All procedures were completed without intraoperative
or postoperative complications. CONCLUSIONS: This combined procedure was
effective and safe for the treatment of high-level or mixed astigmatism.
PMID- 26418427
TI - Possible Further Evidence of Low Genetic Diversity in the El Sidron (Asturias,
Spain) Neandertal Group: Congenital Clefts of the Atlas.
AB - We present here the first cases in Neandertals of congenital clefts of the arch
of the atlas. Two atlases from El Sidron, northern Spain, present respectively a
defect of the posterior (frequency in extant modern human populations ranging
from 0.73% to 3.84%), and anterior (frequency in extant modern human populations
ranging from 0.087% to 0.1%) arch, a condition in most cases not associated with
any clinical manifestation. The fact that two out of three observable atlases
present a low frequency congenital condition, together with previously reported
evidence of retained deciduous mandibular canine in two out of ten dentitions
from El Sidron, supports the previous observation based on genetic evidence that
these Neandertals constituted a group with close genetic relations. Some have
proposed for humans and other species that the presence of skeletal congenital
conditions, although without clinical significance, could be used as a signal of
endogamy or inbreeding. In the present case this interpretation would fit the
general scenario of high incidence of rare conditions among Pleistocene humans
and the specific scenariothat emerges from Neandertal paleogenetics, which points
to long-term small and decreasing population size with reduced and isolated
groups. Adverse environmental factors affecting early pregnancies would
constitute an alternative, non-exclusive, explanation for a high incidence of
congenital conditions. Further support or rejection of these interpretations will
come from new genetic and skeletal evidence from Neandertal remains.
PMID- 26418430
TI - New Method for Removing Thermosensitive Acrylic Punctal Plugs From Lacrimal
Puncta.
AB - PURPOSE: This study explored a new method for removing thermosensitive acrylic
punctal plugs from lacrimal puncta. METHODS: A total of 14 dry eye patients (14
eyes), who required the removal of thermosensitive acrylic punctal plugs from the
lacrimal puncta because of serious complications, were recruited. Among the 14
patients, lacrimal punctal granuloma formation occurred in 3 patients, tearing
occurred in 6 patients, canaliculitis occurred in 3 patients, and chronic
inflammation of the ocular surface occurred in 2 patients. The plugs were removed
using a new method. Briefly, after local anesthesia was administered, a small lid
clamp was used to flip the eyelid outward. After the application of the lid
clamp, the plug could be removed without the use of any additional tools if the
lacrimal punctum was large enough. If the lacrimal punctum was not large enough,
microforceps were used to expand the lacrimal punctum before the application of
the lid clamp. If the plug still could not be removed after the expansion of the
lacrimal punctum, we moved the small lid clamp from the distal side of the
lacrimal ductule to the lacrimal punctum. RESULTS: Using this method, the plug
was successfully removed in all of the patients. CONCLUSIONS: This is a simple
and effective method for removing thermosensitive acrylic punctal plugs from
lacrimal puncta. CLINICAL TRIAL REGISTRATION-URL: :
http://www.clinicaltrials.gov. Unique identifier: ChiCTR-IPR-14005476.
PMID- 26418431
TI - Descemet Membrane Endothelial Keratoplasty for a Decompensated Penetrating
Keratoplasty Graft in the Presence of a Long Glaucoma Tube.
AB - PURPOSE: To describe specific maneuvers and technical modifications to the
standardized "no-touch" technique of Descemet membrane endothelial keratoplasty
(DMEK) to successfully handle the presence of a glaucoma drainage device (GDD)
tube in the anterior chamber of an eye with a failed primary penetrating
keratoplasty (PK) graft. METHODS: A 42-year-old male patient underwent DMEK
because of a failed primary PK graft in his phakic right eye. The patient was
then evaluated at 3 and at 6 months after surgery. RESULTS: A modified no-touch
DMEK technique proved a feasible treatment option for a decompensated primary PK
graft in the presence of a long GDD tube. CONCLUSIONS: With specific technical
modifications DMEK can be successfully performed in eyes with decompensated
primary PK grafts in the presence of a long GDD tube. The very thin DMEK graft
allows positioning between the GDD tube and the failed PK graft, leaving the tube
in place.
PMID- 26418432
TI - Nocardia asteroides Keratitis Resistant to Amikacin.
AB - PURPOSE: To describe 2 cases of Nocardia keratitis resistant to topical
compounded amikacin therapy. METHODS: A 24-year-old woman presented with a
corneal infiltrate. Cultures were taken, and topical moxifloxacin was
administered. Corneal biopsy was performed when clinical status deteriorated,
which confirmed infection with Nocardia. The patient was administered topical
compounded amikacin. When clinical status further deteriorated, she was switched
to compounded trimethoprim-sulfamethoxazole, which resulted in rapid resolution.
Separately, a 22-year-old woman presented with contact lens-related keratitis
that grew Nocardia asteroides. Corneal cultures and drug sensitivity testing
revealed a strain of N. asteroides resistant to amikacin and imipenem, but
sensitive to tobramycin. After a protracted clinical course, the keratitis
ultimately responded to topical tobramycin leaving the patient with a pericentral
corneal scar. CONCLUSIONS: Nocardia keratitis is an atypical infection for which
standard management algorithms exist. However, atypical cases require that these
patients be followed closely for the response to therapy.
PMID- 26418434
TI - Dry Eye Signs and Symptoms Persist During Systemic Neutralization of IL-1beta by
Canakinumab or IL-17A by Secukinumab.
AB - PURPOSE: To evaluate whether inhibition of the proinflammatory cytokines IL-1beta
or IL-17A by canakinumab or secukinumab, respectively, influence the signs and
symptoms of dry eye. METHODS: In a randomized, double-masked, placebo-controlled,
outpatient clinical trial, 72 patients with moderate to severe dry eye were
randomly assigned in a 1:1:1 ratio to treatment with a single intravenous dose of
canakinumab, of secukinumab, or of placebo. Signs and symptoms of dry eye were
evaluated on the treatment day and 1 week, 4 weeks, and 8 weeks after treatment.
The prespecified primary efficacy endpoint was corneal staining in the study eye
4 weeks after treatment. Secondary endpoints included tear production (Schirmer
test), tear film breakup time, conjunctival redness, the ocular surface disease
index (OSDI), the frequency of a desire for a topical ocular lubricant, and
visual acuity. RESULTS: Of the 71 patients included in the analysis of safety,
the rate of adverse events was similar between treatment groups. The course of
corneal staining scores from baseline to 4 weeks, respectively, were for
canakinumab 1.46 to 1.33 (P = 0.62 compared with placebo), for secukinumab 1.46
to 1.23 (P = 0.22), and for placebo 1.68 to 1.42. There were no changes in the
other measures of efficacy beyond what was within the range expected for
stochastic day-to-day variation. CONCLUSIONS: The results suggest that the
inhibition of IL-1beta or IL-17A obtained by systemic administration of
neutralizing drugs does not influence the severity of dry eye.
PMID- 26418435
TI - Novel Treatment for Hemorrhagic Descemet Detachment After Canaloplasty.
AB - PURPOSE: To describe a case of hemorrhagic Descemet membrane detachment after
canaloplasty and to discuss its management using alteplase, a tissue plasminogen
activator (TPA). METHODS: Interventional case report. RESULTS: A 60-year-old
woman with advanced pseudoexfoliation glaucoma developed severe hemorrhagic
Descemet detachment after canaloplasty. Initial anterior chamber and pre-Descemet
washout yielded no improvement. On the fifth postoperative day, the patient
received a novel pre-Descemet treatment using a TPA with an anterior chamber air
bubble. The intracorneal blood clot quickly dissolved intraoperatively with the
Descemet membrane almost completely reattached on postoperative day 1.
CONCLUSIONS: Hemorrhagic Descemet detachment is a rare and serious complication
of canaloplasty. The use of pre-Descemet TPA dissolves the intracorneal blood
clot and helps reattach Descemet membrane, allowing quick rehabilitation of
patient's vision and preserving integrity of the cornea.
PMID- 26418433
TI - Expression of NeuGc on Pig Corneas and Its Potential Significance in Pig Corneal
Xenotransplantation.
AB - PURPOSE: Pigs expressing neither galactose-alpha1,3-galactose (Gal) nor N
glycolylneuraminic acid (NeuGc) take xenotransplantation one step closer to the
clinic. Our aims were (1) to document the lack of NeuGc expression on corneas and
aortas and cultured endothelial cells [aortic endothelial cells (AECs); corneal
(CECs)] of GTKO/NeuGcKO pigs, and (2) to investigate whether the absence of NeuGc
reduced human antibody binding to the tissues and cells. METHODS: Wild-type (WT),
GTKO, and GTKO/NeuGcKO pigs were used for the study. Human tissues and cultured
cells were negative controls. Immunofluorescence staining was performed using
anti-Gal and anti-NeuGc antibodies, and human IgM and IgG binding to tissues was
determined. Flow cytometric analysis was used to determine Gal and NeuGc
expression on cultured CECs and AECs and to measure human IgM/IgG binding to
these cells. RESULTS: Both Gal and NeuGc were detected on WT pig corneas and
aortas. Although GTKO pigs expressed NeuGc, neither humans nor GTKO/NeuGcKO pigs
expressed Gal or NeuGc. Human IgM/IgG binding to corneas and aortas from GTKO and
GTKO/NeuGcKO pigs was reduced compared with binding to WT pigs. Human antibody
binding to GTKO/NeuGcKO AECs was significantly less than that to GTKO AECs, but
there was no significant difference in binding between GTKO and GTKO/NeuGcKO
CECs. CONCLUSIONS: The absence of NeuGc on GTKO aortic tissue and AECs is
associated with reduced human antibody binding, and possibly will provide a
better outcome in clinical xenotransplantation using vascularized organs. For
clinical corneal xenotransplantation, the absence of NeuGc expression on
GTKO/NeuGcKO pig corneas may not prove an advantage over GTKO corneas.
PMID- 26418436
TI - Five-Year Incidence and Predictors for Pterygium in a Rural Community in China:
The Yunnan Minority Eye Study.
AB - PURPOSE: To determine the 5-year cumulative incidence of pterygium and its
associated predictors in the Bai Chinese population in a rural community.
METHODS: This population-based study included 2133 subjects aged 50 years or
older in 2010 and was repeated in 2015 with 1520 subjects (71.3%) participating
in the follow-up examination. Participants with pterygium in either eye in 2010
were excluded from the analysis related to incidence. Anterior segment
examination was performed without pupil dilation using a slit lamp, and pterygium
was defined as a raised fleshy triangular fibrovascular tissue growth of the
conjunctiva encroaching onto the clear cornea. RESULTS: The 5-year cumulative
incidence of pterygium was 6.8% [95% confidence interval (CI), 5.2-8.4] and was
significantly higher in women compared with men (8.8% vs. 3.8%; P = 0.003). The
age-specific incidence was 7.7%, 6.5%, and 5.6% in those aged 50-59, 60-69, 70
years, or older at the baseline, respectively. Outdoor occupation was the only
predictor, which remained to be significantly associated with a higher incidence
of pterygium in multivariate analysis (odds ratio = 2.52, 95% CI, 1.27-4.95). The
predictive effect of outdoor occupation on incident pterygium was moderate with
an area under the curve in the receiver operating characteristic analysis of 0.59
(95% CI, 0.53-0.66). CONCLUSIONS: The incidence of pterygium in this rural cohort
was higher compared to a previous report in Chinese in urban areas. The findings
are important for health policy makers to project future burden of pterygium and
make proper decisions on health resource allocation.
PMID- 26418437
TI - Body Plethysmography is Helpful for COPD Diagnosis, Determination of Severity,
Phenotyping, and Response to Therapy.
PMID- 26418438
TI - Lethal bacterial trap: Cationic surface for endodontic sealing.
AB - Insoluble antibacterial cationic nanoparticles have been previously shown to have
potent and long-lasting antibacterial properties. Our tested hypothesis was that
root canal pathogens will be attracted to and eliminated when exposed to epoxy
resin-based surfaces incorporating cationic nanoparticles. In our research, an
epoxy resin-based surface incorporating quaternary ammonium polyethyleneimine
(QPEI) nanoparticles was evaluated. Surface characterization was performed using
atomic force microscopy and X-ray photoelectron spectra. The surface anti
Enterococcus faecalis effect was evaluated in an anti-gravitational model. Cell
membrane potential, viability, biofilm thickness, and biomass were tested using
flow cytometry and confocal laser scanning microscopy. Additionally, the
antibiofilm activity of the bacterial supernatant was assessed. The surface
characterization showed QPEI nanoparticle embedment on the modified sealer. The
epoxy resin-based surface incorporating the QPEI nanoparticles actively attracted
bacteria, causing membrane destabilization, and bacterial death. The supernatant
of bacteria pre-exposed to QPEI showed an antibacterial effect. In conclusion,
the tested epoxy resin-based surface incorporating QPEI nanoparticles traps and
kills bacteria. The nanoparticles attracted bacteria, reducing their viability,
and promoting cell death.
PMID- 26418439
TI - Enhanced mucosal healing with curcumin in animal oral ulcer model.
AB - OBJECTIVES/HYPOTHESIS: Oral ulcers are very common and can compromise the quality
of life of patients with pain. The objective of this study was to evaluate
mucosal healing with curcumin in an animal oral ulcer model. STUDY DESIGN:
Experimental study. METHODS: Twenty New Zealand white rabbits were used. Round
filter paper 6 mm in diameter was soaked with 15 MUl 50% acetic acid and applied
over the upper labial gingiva, creating a uniform circular ulcer. After creation
of an oral ulcer, curcumin, the active substance in tumeric, was applied twice
over the ulcer in the experimental group but not in the control group. The ulcer
area was calculated by maximal (D) and minimal (d) diameter : pi * D * d/4. All
animals were weighed, and the area was measured on days 0, 7, and 14. On days 7
and 14, half of the animals were sacrificed and gingival specimens were acquired.
RESULTS: Curcumin treatment exhibited accelerated healing such that the gross
appearance of the ulcer demonstrated a recognizable difference in wound healing
between the curcumin-treated and control groups with time. Weight loss was
observed after the creation of oral ulcer in the control group. However, the
curcumin-treated group gained weight with time, resulting in a significant weight
difference. On day 14, epithelial regeneration was completed in the treated group
but incomplete in the control group. CONCLUSION: Topical application of curcumin
enhanced the wound-healing process of oral ulcer in the animal model, which
implicate that curcumin can be used as an effective and safe medical tool in the
treatment of oral ulcer. LEVEL OF EVIDENCE: NA.
PMID- 26418440
TI - Injectable and Self-Healing Dynamic Hydrogels Based on Metal(I)
Thiolate/Disulfide Exchange as Biomaterials with Tunable Mechanical Properties.
AB - Despite numerous strategies involving dynamic covalent bonds to produce self
healing hydrogels with similar frequency-dependent stiffness to native tissues,
it remains challenging to use biologically relevant thiol/disulfide exchange to
confer such properties to polymeric networks. Herein, we report a new method
based on Metal(I) [Au(I) or Ag(I)] capping to protect thiolates from aerial
oxidation without preventing thiolate/disulfide exchange. Dynamic hydrogels were
readily prepared by injecting simultaneously aqueous solutions of commercially
available HAuCl4 and 4-arm thiol-terminated polyethylene glycol [(PEGSH)4],
resulting in a network containing a mixture of Au(I)-thiolate (Au-S) and
disulfide bonds (SS). While the dynamic properties of the hydrogel were closely
dependent on the pH, the mechanical properties could be easily tuned by adjusting
(PEGSH)4 concentration and amount of Au-S, as judged by dynamic rheology studies.
Permanent Au-S/SS exchange at physiological pH conferred self-healing behavior
and frequency-dependent stiffness to the hydrogel. In addition, in vitro studies
confirmed that Au-based dynamic material was not cytotoxic to human dermal
fibroblasts, demonstrating its potential use as a medical device. Dynamic
hydrogels obtained using Ag(I) ions demonstrated that the exchange reaction was
not affected by the nature of the Metal(I) capping. Finally, this efficient
thiolate capping strategy offers a simple way to produce injectable and self
healing dynamic hydrogels from virtually any thiol-containing polymers.
PMID- 26418441
TI - Can we ease the financial burden of colonoscopy? Using real-time endoscopic
assessment of polyp histology to predict surveillance intervals.
AB - BACKGROUND: Polyps identified at colonoscopy are predominantly diminutive (<5 mm)
with a small risk (>1%) of high-grade dysplasia or carcinoma; however, the cost
of histological assessment is substantial. AIM: The aim of this study was to
determine whether prediction of colonoscopy surveillance intervals based on real
time endoscopic assessment of polyp histology is accurate and cost effective.
METHODS: A prospective cohort study was conducted across a tertiary care and
private community hospital. Ninety-four patients underwent colonoscopy and
polypectomy of diminutive (<=5 mm) polyps from October 2012 to July 2013,
yielding a total of 159 polyps. Polyps were examined and classified according to
the Sano-Emura classification system. The endoscopic assessment (optical
diagnosis) of polyp histology was used to predict appropriate colonoscopy
surveillance intervals. The main outcome measure was the accuracy of optical
diagnosis of diminutive colonic polyps against the gold standard of histological
assessment. RESULTS: Optical diagnosis was correct in 105/108 (97.2%) adenomas.
This yielded a sensitivity, specificity and positive and negative predictive
values (with 95%CI) of 97.2% (92.1-99.4%), 78.4% (64.7-88.7%), 90.5% (83.7-95.2%)
and 93% (80.9-98.5%) respectively. Ninety-two (98%) patients were correctly
triaged to their repeat surveillance colonoscopy. Based on these findings, a cut
and discard approach would have resulted in a saving of $319.77 per patient.
CONCLUSION: Endoscopists within a tertiary care setting can accurately predict
diminutive polyp histology and confer an appropriate surveillance interval with
an associated financial benefit to the healthcare system. However, limitations to
its application in the community setting exist, which may improve with further
training and high-definition colonoscopes.
PMID- 26418443
TI - CONE DENSITY LOSS ON ADAPTIVE OPTICS IN EARLY MACULAR TELANGIECTASIA TYPE 2.
AB - PURPOSE: To determine whether cone photoreceptors are impaired early in macular
telangiectasia type 2 (MacTel 2) progression. METHODS: Eight patients with MacTel
2 lacking intraretinal cavitation underwent multimodal retinal imaging including
adaptive optics. Cone packing metrics were determined in 5 sampling windows at
different eccentricities from the fovea. Results were compared with a previously
established normative database. RESULTS: In MacTel 2 eyes, cone density was
significantly lower than normal at all eccentricities (P < 0.0001). Mean cone
spacing and mean percentage of hexagonally organized cone photoreceptors were
respectively significantly larger and lower than normal at all eccentricities (P
= 0.0488 and P < 0.0001). In MacTel 2 patients, adaptive optics showed an
irregular patchy disturbance of the cone mosaic corresponding to some
fragmentation of the interdigitation zone on optical coherence tomography. The
ellipsoid zone remained intact in the studied area. CONCLUSION: Adaptive optics
showed that the macular cone density was lower than normal even outside the
telangiectasia in MacTel 2 lacking intraretinal cavitation, although the
ellipsoid zone remained intact on optical coherence tomography. These findings do
not indicate that the cone density loss is causative of the disease as it might
be secondary to Muller cell or rod loss in this area. However, cone density
assessment could become a useful parameter to monitor disease progression.
PMID- 26418442
TI - EVALUATION OF MULTIPLE DEXAMETHASONE INTRAVITREAL IMPLANTS IN PATIENTS WITH
MACULAR EDEMA ASSOCIATED WITH RETINAL VEIN OCCLUSION.
AB - BACKGROUND: Limited data have evaluated multiple injections of the dexamethasone
700 MUg implant (DEX) (Ozurdex; Allergan, Inc.) for cystoid macular edema (CME)
secondary to retinal vein occlusion (RVO) over an extended regimen. METHODS: This
retrospective study evaluated patients treated with DEX for CME associated with
RVO. Each patient had ophthalmologic evaluation, optical coherence tomography
(OCT), and 4 weeks to 6 weeks follow-up intervals. Retreatment criterion was
fluid on OCT. Outcome measures included best-corrected visual acuity, intraocular
pressure (IOP), central macular thickness on OCT, fluid resolution on OCT, and
required treatment for elevated IOP and cataract. RESULTS: Thirty-one patients
had 82 DEX injections, with 19 patients having >=2, 12 having >=3, 10 having >=4,
6 having >=5, and 4 having >=6 DEX injections. All patients were followed at
least 12 weeks and had a mean follow-up period of 344.94 days. Fourteen patients
(45%) developed ocular hypertension (>=22 mmHg), and 40% of phakic patients
required cataract surgery. Mean interval of OCT fluid resolution was 52 days
(range, 28-245; SD, +/-8), and mean retreatment interval was 119 days (range, 42
309; SD, +/-9). No patients required glaucoma surgery or developed
endophthalmitis. CONCLUSION: This study suggests that repeated, as needed, DEX
injections for CME associated with RVO may be performed. Patients should be
monitored and treated for ocular hypertension and cataract progression.
PMID- 26418444
TI - TREATMENT OF PERSISTENTLY OPEN MACULAR HOLES WITH HEAVY SILICONE OIL (DENSIRON
68) VERSUS C2F6. A PROSPECTIVE RANDOMIZED STUDY.
AB - PURPOSE: To compare the efficacy of a mixture of silicone oil and
perfluorohexyloctane (Densiron 68) with C2F6 gas endotamponade in the retreatment
of persistently open full-thickness macular holes. METHODS: In this prospective
randomized study, 21 consecutive patients who were unsuccessfully operated on for
large idiopathic full-thickness macular hole were randomly assigned to undergo a
second vitrectomy with 20% perfluoroethane gas (C2F6, Group A) or with Densiron
68 tamponade (Group B). PRIMARY OUTCOMES: Endpoint (12 months) full-thickness
macular hole closure rate by spectral domain optical coherence tomography and
logMAR corrected distance visual acuity. SECONDARY OUTCOMES: postoperative
adverse events. RESULTS: The mean diameter of macular holes before the second
pars plana vitrectomy was 680.3 +/- 120.8 MUm and 740.5 +/- 105.3 MUm in Groups A
and B, respectively (P = 0.237); mean preoperative corrected distance visual
acuity was 0.96 +/- 0.36 logMAR and 1.12 +/- 0.35 logMAR, respectively (P =
0.315). Endpoint full-thickness macular hole closure was obtained in 30% of
patients (3/10) in Group A and in 82% (9/11) in Group B (P = 0.030). Corrected
distance visual acuities were, respectively, 0.80 +/- 0.25 logMAR and 0.55 +/-
0.20 logMAR, with significant intergroup difference (P = 0.019); corrected
distance visual acuity increased in Group B only (P = 0.003). No differences in
complications were found. CONCLUSION: The results indicate that Densiron 68
tamponade could be a useful, safe, and more efficacious method than gas tamponade
to retreat persisting macular holes.
PMID- 26418445
TI - VOLUMETRIC ASSESSMENT OF THE RESPONSIVENESS OF PIGMENT EPITHELIAL DETACHMENTS IN
NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TO INTRAVITREAL BEVACIZUMAB.
AB - PURPOSE: To determine baseline factors that can predict the response of pigment
epithelial detachments (PEDs) in neovascular age-related macular degeneration to
treatment with intravitreal bevacizumab (IVB). METHODS: Patients with newly
diagnosed neovascular age-related macular degeneration and PED who were treated
exclusively with IVB were included. Response to treatment was defined by change
in PED volume (determined using spectral-domain optical coherence tomography).
PEDs were classified as either predominantly serous or fibrovascular.
Multivariable regression and receiver operating characteristic analyses were
performed. RESULTS: A total of 48 eyes were identified (mean follow-up time 73
weeks). Overall, the response to the first IVB treatment was predictive of the
response to treatment at the final visit (P = 0.015). Serous PEDs had a greater
decrease in volume at the final visit (P = 0.008). With respect to both PED
types, a decrease in PED volume of 21% after the first IVB treatment was
predictive of an overall decrease in volume of 30% at the final visit
(sensitivity 83%, specificity 76%). CONCLUSION: In neovascular age-related
macular degeneration, serous PEDs respond more favorably to IVB than
fibrovascular PEDs. Overall, for both types of PED, the response to the first
treatment is predictive of the final response to treatment. Taken together, the
results would suggest that if there is less than 21% reduction in PED volume
after the first IVB treatment, and/or the PED is predominantly fibrovascular,
then switching to another antivascular endothelial growth factor agent should be
considered.
PMID- 26418446
TI - CORRELATION OF INCREASED INTRAVITREOUS WNT3A WITH VASCULAR ENDOTHELIAL GROWTH
FACTOR IN PROLIFERATIVE DIABETIC RETINOPATHY.
AB - PURPOSE: To investigate Wnt3a and vascular endothelial growth factor (VEGF)
levels in the vitreous fluid of patients with proliferative diabetic retinopathy
(PDR) and to examine their correlation with PDR activity. METHODS: Vitreous
samples from 45 eyes with PDR and 28 eyes with nondiabetic macular disease were
collected. Active PDR was present in 24 patients and inactive PDR in 21 patients,
according to retinal neovascularization. The Wnt3a and VEGF level of vitreous
fluid samples were measured by enzyme-linked immunosorbent assay. RESULTS:
Comparison revealed that mean intravitreal levels of Wnt3a increased
significantly in PDR eyes compared with control eyes (13.55 ng/mL vs. 1.57 ng/mL,
P < 0.001). The mean VEGF concentrations in the vitreous fluid of patients with
PDR were also higher than those in nondiabetic controls, with the values being
723.21 pg/mL and 20.81 pg/mL, respectively (P < 0.001). In addition, vitreous
concentrations of Wnt3a and VEGF were significantly higher in active PDR than in
eyes with inactive PDR (P = 0.016 and P = 0.008, respectively). Furthermore, a
significant positive correlation was detected between Wnt3a and VEGF levels in
the vitreous. CONCLUSION: Intravitreous levels of Wnt3a and VEGF in patients with
PDR are increased and correlated mutually. Wnt3a may be an important player in
the development of diabetic retinopathy and its activity in vitreous fluid can be
biomarker of PDR.
PMID- 26418447
TI - SUPPLEMENTAL SCLERAL BUCKLE IN VITRECTOMY FOR THE REPAIR OF RHEGMATOGENOUS
RETINAL DETACHMENT: A Systematic Review of Literature and Meta-Analysis.
AB - PURPOSE: To evaluate the effect of supplemental scleral buckle (SB) in pars plana
vitrectomy (PPV) for rhegmatogenous retinal detachment. METHODS: MEDLINE, EMBASE,
and CENTRAL were searched to identify studies comparing PPV with supplemental SB
(PPV + SB) to PPV alone for the repair of rhegmatogenous retinal detachment. The
outcome measures were primary and final reattachment rates, and postoperative
complications. Odds ratio with 95% confidence interval in random effects for the
comparison of outcomes between PPV + SB and PPV alone was calculated. RESULTS:
Ten studies consisting of 1,704 patients were included. Meta-analysis showed that
the overall primary reattachment rate was significantly higher in PPV + SB than
PPV alone (odds ratio, 1.70; 95% confidence interval, 1.21-2.39; P = 0.002). The
final reattachment rate was equally high in both groups. Postoperative
development of epiretinal membrane was more frequent in PPV + SB than in PPV
alone (odds ratio, 1.89; 95% confidence interval, 1.30-2.76; P = 0.001), whereas
no significant difference in postoperative development of macular edema,
proliferative vitreoretinopathy, or elevation of intraocular pressure was found.
CONCLUSION: Supplemental SB increases the primary reattachment rate in PPV for
rhegmatogenous retinal detachment, although final reattachment rate was equally
high with or without SB.
PMID- 26418448
TI - Thru-the-Trocar Administration of Dexamethasone Intravitreal Implant During 23-G
Pars Plana Vitrectomy: A Small Case Series.
PMID- 26418449
TI - Vascularized Drusen: Slowly Progressive Type 1 Neovascularization Mimicking
Drusenoid Retinal Pigment Epithelium Elevation.
PMID- 26418450
TI - Perfluoro-n-octane Assisted Free Internal Limiting Membrane Flap Technique for
Recurrent Macular Hole.
PMID- 26418451
TI - Rosin Surfactant QRMAE Can Be Utilized as an Amorphous Aggregate Inducer: A Case
Study of Mammalian Serum Albumin.
AB - Quaternary amine of diethylaminoethyl rosin ester (QRMAE), chemically synthesized
biocompatible rosin based cationic surfactant, has various biological
applications including its use as a food product additive. In this study, we
examined the amorphous aggregation behavior of mammalian serum albumins at pH
7.5, i.e., two units above their isoelectric points (pI ~5.5), and the roles
played by positive charge and hydrophobicity of exogenously added rosin
surfactant QRMAE. The study was carried out on five mammalian serum albumins,
using various spectroscopic methods, dye binding assay, circular dichroism and
electron microscopy. The thermodynamics of the binding of mammalian serum
albumins to cationic rosin modified surfactant were established using isothermal
titration calorimetry (ITC). It was observed that a suitable molar ratio of
protein to QRMAE surfactant enthusiastically induces amorphous aggregate
formation at a pH above two units of pI. Rosin surfactant QRMAE-albumins
interactions revealed a unique interplay between the initial electrostatic and
the subsequent hydrophobic interactions that play an important role towards the
formation of hydrophobic interactions-driven amorphous aggregate. Amorphous
aggregation of proteins is associated with varying diseases, from the formation
of protein wine haze to the expansion of the eye lenses in cataract, during the
expression and purification of recombinant proteins. This study can be used for
the design of novel biomolecules or drugs with the ability to neutralize
factor(s) responsible for the aggregate formation, in addition to various other
industrial applications.
PMID- 26418453
TI - The effects of familial risk and parental resolution on parenting a child with
mild intellectual disability.
AB - The current study investigated the manner by which family risk moderates the
links between parental state of resolution with a child's diagnosis and both
parent-child interaction and parental stress. The sample included 72 families
with 4-7-year-old children (M=5.53, SD=0.73) diagnosed with mild intellectual
disability. Parents reported on their resolution state and parental stress, and
parent-child interactions were videotaped and analyzed. Results indicated that in
families where mothers or fathers were unresolved rather than resolved, mother
child interactions were less positive only in the context of high family risk.
The father-child interaction was not found to be affected by family risk and
parental resolution. Interestingly, mothers in low family risk situations who
were resolved reported the lowest level of parental stress, suggesting a "double
buffer" effect, whereas fathers with high family risk who were unresolved
experienced the highest levels of parental stress, suggesting a "double risk"
effect.
PMID- 26418452
TI - Deletion of Estrogen Receptor Beta in Osteoprogenitor Cells Increases Trabecular
but Not Cortical Bone Mass in Female Mice.
AB - Although the role of ERalpha in regulating bone metabolism has been extensively
studied, ERbeta has been largely dismissed as a relevant modulator of bone mass.
Previous studies examining ERbeta utilized a germline knockout mouse expressing
transcript variants of ERbeta and displaying systemic hormonal changes that
confounded interpretation of the skeletal phenotype. Thus, we used a conditional
ERbeta mouse model to achieve deletion of ERbeta specifically in early
osteoprogenitor cells using the Prx1-Cre driver. We observed marked increases in
the trabecular bone volume fraction (of 58% [p < 0.003] and 93% [p < 0.0003] in 6
and 12-week-old female ERbeta(Prx1-CKO) mice, respectively) but no changes in
cortical bone. Serum estradiol and IGF-I levels were unaltered in ERbeta(Prx1
CKO) mice. Bone formation and resorption indices by histomorphometry and serum
assays were unchanged in these mice, suggesting that alterations in bone turnover
may have occurred early in development. However, the ratio of colony-forming unit
osteoblasts (CFU-OBs) to CFU-fibroblasts (CFU-Fs) was increased in bone marrow
cultures from ERbeta(Prx1-CKO) compared with control mice, indicating increased
differentiation of osteoblast precursor cells into osteoblasts in ERbeta(Prx1
CKO) mice. Detailed quantitative polymerase chain reaction analyses of 128 genes
in 16 prespecified pathways revealed significant downregulation of 11 pathways in
ERbeta(Prx1-CKO) mice. Thus, deletion of ERbeta specifically in osteoblast
lineage cells, in the absence of all splice variants, increases trabecular bone
mass and modulates multiple pathways related to bone metabolism. These findings
suggest that pharmacological inhibition of ERbeta in bone may provide a novel
approach to treat osteoporosis.
PMID- 26418454
TI - Feasibility of bioelectrical impedance analysis in persons with severe
intellectual and visual disabilities.
AB - BACKGROUND: Body composition measurements provide important information about
physical fitness and nutritional status. People with severe intellectual and
visual disabilities (SIVD) have an increased risk for altered body composition.
Bioelectrical impedance analysis (BIA) has been evidenced as a reliable and non
invasive method to asses body composition in healthy persons and various patient
populations; however, currently, there is no feasible method available to
determine body composition in people with SIVD. In this study, therefore, we
aimed to assess the feasibility of BIA measurements in persons with SIVD.
METHODS: In 33 participants with SIVD and Gross Motor Functioning Classification
System (GMFCS) Scale I, II, III, or IV, two BIA measurements were sequentially
performed employing Resistance and Reactance in Ohm and fat-free mass (FFM) in kg
as outcome variables, utilizing the Bodystat((r)) QuadScan 4000. Feasibility was
considered sufficient if >= 80% of the first measurement was performed
successfully. Agreement between two repeated measurements was determined by using
the paired t-test and Intraclass Correlation Coefficient (ICC; two way random,
absolute agreement). Bland-Altman analyses were utilized to determine limits of
agreement (LOAs) and systematic error. Agreement was considered acceptable if
LOAs were <10% of the mean of the first measurement. RESULTS: The first BIA
measurements were completed successfully in 88% of the participants. The paired t
test demonstrated no significant differences in Resistance, Reactance, and FFM
between BIA Measurements 1 and 2 (P=0.140, 0.091, and 0.866). ICC was 0.965 (95%
CI: 0.922-0.984) for Resistance; 0.858 (95% CI: 0.705-0.934) for Reactance; and
0.992 (95% CI: 0.982-0.996) for FFM. LOAs expressed as a percentage of the mean
of Measurement 1 were 6.1% for Resistance, 17.6% for Reactance, and 3.8% for FFM.
CONCLUSIONS: The results of this study suggest that BIA measurements seem to be
feasible in persons with SIVD. Although these results require confirmation in a
more extensive sample of persons with SIVD, the findings of this study are an
important first step in the assessment of applicability of BIA measurements for
non-invasive monitoring of physical fitness and nutritional status of persons
with SIVD.
PMID- 26418457
TI - Single-Crystal-Like Organic Thin-Film Transistors Fabricated from Dinaphtho[2,3
b:2',3'-f]thieno[3,2-b]thiophene (DNTT) Precursor-Polystyrene Blends.
AB - High-mobility short-channel organic thin-film transistors fabricated using a
dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]-thio--phene (DNTT) precursor (5,14-N-
phenylmaleimide DNTT, endo-isomer-rich fraction) and polystyrene (PS) blends are
reported. The DNTT grains are "single-crystal"-like and the field-effect mobility
of the devices ranges up to 4.7 cm(2) V(-1) s(-1). The PS layer functions as a
hydrophobic passivation layer on the Si/SiO2 substrate.
PMID- 26418455
TI - BMPER Promotes Epithelial-Mesenchymal Transition in the Developing Cardiac
Cushions.
AB - Formation of the cardiac valves is an essential component of cardiovascular
development. Consistent with the role of the bone morphogenetic protein (BMP)
signaling pathway in cardiac valve formation, embryos that are deficient for the
BMP regulator BMPER (BMP-binding endothelial regulator) display the cardiac valve
anomaly mitral valve prolapse. However, how BMPER deficiency leads to this defect
is unknown. Based on its expression pattern in the developing cardiac cushions,
we hypothesized that BMPER regulates BMP2-mediated signaling, leading to fine
tuned epithelial-mesenchymal transition (EMT) and extracellular matrix
deposition. In the BMPER-/- embryo, EMT is dysregulated in the atrioventricular
and outflow tract cushions compared with their wild-type counterparts, as
indicated by a significant increase of Sox9-positive cells during cushion
formation. However, proliferation is not impaired in the developing BMPER-/-
valves. In vitro data show that BMPER directly binds BMP2. In cultured
endothelial cells, BMPER blocks BMP2-induced Smad activation in a dose-dependent
manner. In addition, BMP2 increases the Sox9 protein level, and this increase is
inhibited by co-treatment with BMPER. Consistently, in the BMPER-/- embryos, semi
quantitative analysis of Smad activation shows that the canonical BMP pathway is
significantly more active in the atrioventricular cushions during EMT. These
results indicate that BMPER negatively regulates BMP-induced Smad and Sox9
activity during valve development. Together, these results identify BMPER as a
regulator of BMP2-induced cardiac valve development and will contribute to our
understanding of valvular defects.
PMID- 26418456
TI - TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype.
AB - OBJECTIVE: Mutations in TPM3, encoding Tpm3.12, cause a clinically and
histopathologically diverse group of myopathies characterized by muscle weakness.
We report two patients with novel de novo Tpm3.12 single glutamic acid deletions
at positions DeltaE218 and DeltaE224, resulting in a significant hypercontractile
phenotype with congenital muscle stiffness, rather than weakness, and respiratory
failure in one patient. METHODS: The effect of the Tpm3.12 deletions on the
contractile properties in dissected patient myofibers was measured. We used
quantitative in vitro motility assay to measure Ca(2+) sensitivity of thin
filaments reconstituted with recombinant Tpm3.12 DeltaE218 and DeltaE224.
RESULTS: Contractility studies on permeabilized myofibers demonstrated reduced
maximal active tension from both patients with increased Ca(2+) sensitivity and
altered cross-bridge cycling kinetics in DeltaE224 fibers. In vitro motility
studies showed a two-fold increase in Ca(2+) sensitivity of the fraction of
filaments motile and the filament sliding velocity concentrations for both
mutations. INTERPRETATION: These data indicate that Tpm3.12 deletions DeltaE218
and DeltaE224 result in increased Ca(2+) sensitivity of the troponin-tropomyosin
complex, resulting in abnormally active interaction of the actin and myosin
complex. Both mutations are located in the charged motifs of the actin-binding
residues of tropomyosin 3, thus disrupting the electrostatic interactions that
facilitate accurate tropomyosin binding with actin necessary to prevent the on
state. The mutations destabilize the off-state and result in excessively
sensitized excitation-contraction coupling of the contractile apparatus. This
work expands the phenotypic spectrum of TPM3-related disease and provides
insights into the pathophysiological mechanisms of the actin-tropomyosin complex.
PMID- 26418459
TI - Identification of Astrotactin2 as a Genetic Modifier That Regulates the Global
Orientation of Mammalian Hair Follicles.
AB - Planar cell polarity (PCP) signaling controls the global orientation of surface
structures, such as hairs and bristles, in both vertebrates and invertebrates. In
Frizzled6(-/-) (Fz6(-/-)) mice, hair follicle orientations on the head and back
are nearly random at birth, but reorient during early postnatal development to
eventually generate a nearly parallel anterior-to-posterior array. We report the
identification of a naturally occurring exon 5 deletion in Astrotactin2 (Astn2)
that acts as a recessive genetic modifier of the Fz6(-/-) hair patterning
phenotype. A genetically engineered Astn2 exon 5 deletion recapitulates the
modifier phenotype. In Fz6(-/-);Astn2(ex5del/del) mice, hair orientation on the
back is subtly biased from posterior-to-anterior, leading to a 180-degree
orientation reversal in mature mice. These experiments suggest that Astn2, an
endosomal membrane protein, modulates PCP signaling.
PMID- 26418460
TI - Interferon-gamma-Induced Nitric Oxide Synthase-2 Contributes to Blood/Brain
Barrier Dysfunction and Acute Mortality in Experimental Streptococcus pneumoniae
Meningitis.
AB - The proinflammatory cytokine interferon-gamma (IFNgamma) recently was shown to
play a crucial role in experimental pneumococcal meningitis (PM) pathogenesis,
and we aimed in this study to investigate IFNgamma-driven nitric oxide synthase-2
(NOS2)-mediated pathogenesis of murine PM. We demonstrate that costimulation of
toll-like receptors and IFNgamma receptors was synergistic for NOS2 expression in
cultured murine microglia. Using an experimental PM model, wild-type mice treated
with anti-IFNgamma antibody, as well as IFNgamma and NOS2 gene knockout (GKO)
mice, were inoculated intracerebroventricularly with 10(3) colony-forming units
of Streptococcus pneumoniae (WU2 strain). Mice were monitored daily during a 200
h disease course to assess survival rate and blood-brain barrier (BBB)
permeability measured at 48 h. IFNgamma deficiency was protective in PM, with an
approximate 3-fold increase in survival rates in both antibody-treated and
IFNgamma GKO mice compared to controls (P < 0.01). At 48 h postinoculation, brain
NOS2 mRNA expression was significantly increased in an IFNgamma-dependent manner.
Mortality was significantly delayed in NOS2 GKO mice compared to controls (P <
0.01), and BBB dysfunction was reduced by 54% in IFNgamma GKO mice and abolished
in NOS2 GKO. These data suggest that IFNgamma-dependent expression of NOS2 in the
brain contributes to BBB breakdown and early mortality in murine PM.
PMID- 26418461
TI - Surface Plasmon Polariton Cross-Coupling Enhanced Forward Emission from Insulator
Metal-Capped ZnO Films.
AB - Increasing light extraction efficiency in the forward direction is being
extensively pursued due to its crucial role in realizing top-emitting organic and
inorganic light emitting devices. Various surface plasmon polariton (SPP)-based
strategies for emission enhancement and light extraction have been developed to
improve the top-emitting efficiency of these devices. However, the role of
surface roughness of both semiconductor film and metal electrode in improving the
emission efficiency of a practical device has not been thoroughly studied yet. In
this work, the influence of surface roughness of a top metal electrode on the
photoluminescence enhancement of a ZnO thin film is investigated experimentally
and numerically based on an insulator-metal-semiconductor system. It is found
that the generic surface roughness of the metal electrode plays an encouraging
role in increasing the forward-emission intensity by facilitating cross-coupling
of SPPs on the two opposite sides of the metal layer. More importantly, the
forward emission can be further enhanced by capping a high-index polymer layer on
the metal electrode to bridge the momentum mismatch between the two SPPs modes.
The experimental observations are well explained by the SPPs cross-coupling
mechanism that models the radiation power of a dipolar emitter underneath the
metal electrode as a function of the metal surface roughness. Our work opens up
the possibility of using cross-coupling of SPPs as an effective means to
fabricate high-brightness top-emitting devices without the need of complicated
nanoscale patterning.
PMID- 26418458
TI - Chemical, Thermal and Spectroscopic Methods to Assess Biodegradation of Winery
Distillery Wastes during Composting.
AB - The objective of this work was to study the co-composting process of wastes from
the winery and distillery industry with animal manures, using the classical
chemical methods traditionally used in composting studies together with advanced
instrumental methods (thermal analysis, FT-IR and CPMAS 13C NMR techniques), to
evaluate the development of the process and the quality of the end-products
obtained. For this, three piles were elaborated by the turning composting system,
using as raw materials winery-distillery wastes (grape marc and exhausted grape
marc) and animal manures (cattle manure and poultry manure). The classical
analytical methods showed a suitable development of the process in all the piles,
but these techniques were ineffective to study the humification process during
the composting of this type of materials. However, their combination with the
advanced instrumental techniques clearly provided more information regarding the
turnover of the organic matter pools during the composting process of these
materials. Thermal analysis allowed to estimate the degradability of the
remaining material and to assess qualitatively the rate of OM stabilization and
recalcitrant C in the compost samples, based on the energy required to achieve
the same mass losses. FT-IR spectra mainly showed variations between piles and
time of sampling in the bands associated to complex organic compounds (mainly at
1420 and 1540 cm-1) and to nitrate and inorganic components (at 875 and 1384 cm
1, respectively), indicating composted material stability and maturity; while
CPMAS 13C NMR provided semi-quantitatively partition of C compounds and
structures during the process, being especially interesting their variation to
evaluate the biotransformation of each C pool, especially in the comparison of
recalcitrant C vs labile C pools, such as Alkyl /O-Alkyl ratio.
PMID- 26418462
TI - Ultrafast Photoinduced Symmetry-Breaking Charge Separation and Electron Sharing
in Perylenediimide Molecular Triangles.
AB - We report on a visible-light-absorbing chiral molecular triangle composed of
three covalently linked 1,6,7,12-tetra(phenoxy)perylene-3,4:9,10
bis(dicarboximide) (PDI) units. The rigid triangular architecture reduces the
electronic coupling between the PDIs, so ultrafast symmetry-breaking charge
separation is kinetically favored over intramolecular excimer formation, as
revealed by femtosecond transient absorption spectroscopy. Photoexcitation of the
PDI triangle dissolved in CH2Cl2 gives PDI(+*)-PDI(-*) in tauCS = 12.0 +/- 0.2
ps. Fast subsequent intramolecular electron/hole hopping can equilibrate the six
possible energetically degenerate ion-pair states, as suggested by electron
paramagnetic resonance/electron-nuclear double resonance spectroscopy, which
shows that one-electron reduction of the PDI triangle results in complete
electron sharing among the three PDIs. Charge recombination of PDI(+*)-PDI(-*) to
the ground state occurs in tauCR = 1.12 +/- 0.01 ns with no evidence of triplet
excited state formation.
PMID- 26418464
TI - A Cross Sectional Analysis of Gonococcal and Chlamydial Infections among Men-Who
Have-Sex-with-Men in Cape Town, South Africa.
AB - BACKGROUND: Men-who-have-sex-with-men (MSM) are at high risk of HIV and sexually
transmitted infection (STI) transmission. Asymptomatic STIs are common in MSM and
remain undiagnosed and untreated where syndromic management is advocated.
Untreated STIs could be contributing to high HIV rates. This study investigated
symptomatic (SSTI) and asymptomatic STIs (ASTIs) in MSM in Cape Town. METHODS:
MSM, 18 years and above, were enrolled into this study. Participants underwent
clinical and microbiological screening for STIs. Urine, oro-pharyngeal and anal
swab specimens were collected for STI analysis, and blood for HIV and syphilis
screening. A psychosocial and sexual questionnaire was completed. STI specimens
were analysed for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT)
infection. RESULTS: 200 MSM were recruited with a median age of 32 years (IQR 26
39.5). Their median number of sex partners within the last year was 5 (IQR 2-20).
155/200 (78%) reported only male sex partners while 45/200 (23%) reported sex
with men and women. 77/200 (39%) reported transactional sex. At enrolment, 88/200
(44%) were HIV positive and 8/112 (7%) initially HIV-negative participants
seroconverted during the study. Overall, 47/200 (24%) screened positive for
either NG or CT. There were 32 MSM (16%) infected with NG and 7 (3.5%) of these
men had NG infections at two anatomical sites (39 NG positive results in total).
Likewise, there were 23 MSM (12%) infected with CT and all these men had
infections at only one site. Eight of the 47 men (17%) were infected with both NG
and CT. ASTI was more common than SSTI irrespective of anatomical site, 38 /200
(19%) versus 9/200 (5%) respectively (p<0.001). The anus was most commonly
affected, followed by the oro-pharynx and then urethra. Asymptomatic infection
was associated with transgender identity (OR 4.09 CI 1.60-5.62), >=5 male sex
partners in the last year (OR 2.50 CI 1.16-5.62) and transactional sex (OR 2.33
CI 1.13-4.79) but not with HIV infection. CONCLUSIONS: Asymptomatic STI was
common and would not have been detected using a syndromic management approach.
Although molecular screening for NG/CT is costly, in our study only four MSM
needed to be screened to detect one case. This supports dual NG/CT molecular
screening for MSM, which, in the case of confirmed NG infections, may trigger
further culture-based investigations to determine gonococcal antimicrobial
susceptibility in the current era of multi-drug resistant gonorrhoea.
PMID- 26418465
TI - Exploring Regional Variation in Roost Selection by Bats: Evidence from a Meta
Analysis.
AB - BACKGROUND AND AIMS: Tree diameter, tree height and canopy closure have been
described by previous meta-analyses as being important characteristics in roost
selection by cavity-roosting bats. However, size and direction of effects for
these characteristics varied greatly among studies, also referred to as
heterogeneity. Potential sources of heterogeneity have not been investigated in
previous meta-analyses, which are explored by correlating additional covariates
(moderator variables). We tested whether effect sizes from 34 studies were
consistent enough to reject the null hypothesis that trees selected by bats did
not significantly differ in their characteristics from randomly selected trees.
We also examined whether heterogeneity in tree diameter effect sizes was
correlated to moderator variables such as sex, bat species, habitat type,
elevation and mean summer temperature. METHODS: We used Hedges' g standardized
mean difference as the effect size for the most common characteristics that were
encountered in the literature. We estimated heterogeneity indices, potential
publication bias, and spatial autocorrelation of our meta-data. We relied upon
meta-regression and multi-model inference approaches to evaluate the effects of
moderator variables on heterogeneity in tree diameter effect sizes. RESULTS: Tree
diameter, tree height, snag density, elevation, and canopy closure were
significant characteristics of roost selection by cavity-roosting bats. Size and
direction of effects varied greatly among studies with respect to distance to
water, tree density, slope, and bark remaining on trunks. Inclusion of mean
summer temperature and sex in meta-regressions further explained heterogeneity in
tree diameter effect sizes. CONCLUSIONS: Regional differences in roost selection
for tree diameter were related to mean summer temperature. Large diameter trees
play a central role in roost selection by bats, especially in colder regions,
where they are likely to provide a warm and stable microclimate for reproductive
females. Records of summer temperature fluctuations inside and outside tree
cavities that are used by bats should be included in future research.
PMID- 26418463
TI - Associations Between Physical Fitness Indices and Working Memory in Breast Cancer
Survivors and Age-Matched Controls.
AB - BACKGROUND: This study examined the effects of cardiorespiratory fitness, heart
rate recovery, and physical activity on working memory in breast cancer survivors
and age-matched controls. METHOD: Using a case-control design, 32 women who had
received a breast cancer diagnosis and completed primary treatment within the
past 36-months (11 radiation only; 21 chemotherapy) and 30 age-matched women with
no previous cancer diagnosis completed a n-back continuous performance task
commonly used as an assessment of working memory. In addition, cardiorespiratory
fitness and heart rate recovery were measured during a submaximal graded exercise
test and physical activity was measured using 7-days of accelerometer monitoring.
RESULTS: Breast cancer survivors who had received chemotherapy had poorer heart
rate recovery (p = .010) and engaged in less physical activity than women who had
received radiation only (p = .004) or non-cancer controls (p = .029). Cancer
treatment (radiation; chemotherapy) predicted differences in reaction times on
the 1-back working memory task (p = .029). However, more rapid heart rate
recovery predicted shorter reaction times on the 1-back task in the age-matched
control group (p = .002). All participants with greater cardiorespiratory fitness
displayed greater accuracy independent of disease status on the 1-back task (p =
.017). No significant group differences in reaction times were observed for 2
back target trials between breast cancer survivors and controls. However, greater
total physical activity predicted shorter reaction times in breast cancer
survivors (radiation, chemotherapy) on the 2-back task (p = .014). In addition,
all participants who exhibited more rapid heart rate recovery demonstrated better
greater accuracy regardless of disease status (p = .013). CONCLUSION: These
findings support differences in physical activty participation, heart rate
recovery, and 1- and 2-back working memory reaction times between breast cancer
survivors and age-matched controls. Greater cardiorespiratory fitness, heart rate
recovery, and physical activity were positively associated with better working
memory performance across conditions.
PMID- 26418466
TI - Mammalian Brains Are Made of These: A Dataset of the Numbers and Densities of
Neuronal and Nonneuronal Cells in the Brain of Glires, Primates, Scandentia,
Eulipotyphlans, Afrotherians and Artiodactyls, and Their Relationship with Body
Mass.
AB - Comparative studies amongst extant species are one of the pillars of evolutionary
neurobiology. In the 20th century, most comparative studies remained restricted
to analyses of brain structure volume and surface areas, besides estimates of
neuronal density largely limited to the cerebral cortex. Over the last 10 years,
we have amassed data on the numbers of neurons and other cells that compose the
entirety of the brain (subdivided into cerebral cortex, cerebellum, and rest of
brain) of 39 mammalian species spread over 6 clades, as well as their densities.
Here we provide that entire dataset in a format that is readily useful to
researchers of any area of interest in the hope that it will foster the
advancement of evolutionary and comparative studies well beyond the scope of
neuroscience itself. We also reexamine the relationship between numbers of
neurons, neuronal densities and body mass, and find that in the rest of brain,
but not in the cerebral cortex or cerebellum, there is a single scaling rule that
applies to average neuronal cell size, which increases with the linear dimension
of the body, even though there is no single scaling rule that relates the number
of neurons in the rest of brain to body mass. Thus, larger bodies do not
uniformly come with more neurons--but they do fairly uniformly come with larger
neurons in the rest of brain, which contains a number of structures directly
connected to sources or targets in the body.
PMID- 26418467
TI - Occupant injury in rollover crashes - Contribution of planar impacts with objects
and other vehicles.
AB - Planar impacts with objects and other vehicles may increase the risk and severity
of injury in rollover crashes. The current study compares the frequency of injury
measures (MAIS 2+, 3+, and 4+; fatal; AIS 2+ head and cervical spine; and AIS 3+
head and thorax) as well as vehicle type distribution (passenger car, SUV, van,
and light truck), crash kinematics, and occupant demographics between single
vehicle single event rollovers (SV Pure) and multiple event rollovers to
determine which types of multiple event rollovers can be pooled with SV Pure to
study rollover induced occupant injury. Four different types of multiple event
rollovers were defined: single and multi-vehicle crashes for which the rollover
is the most severe event (SV Prim and MV Prim) and single and multi-vehicle
crashes for which the rollover is not the most severe event (SV Non-Prim and MV
Non-Prim). Information from real world crashes was obtained from the National
Automotive Sampling System - Crashworthiness Data System (NASS-CDS) for the
period from 1995 through 2011. Belted, contained or partially ejected, adult
occupants in vehicles that completed 1-16 lateral quarter turns were assigned to
one of the five rollover categories. The results showed that the frequency of
injury in non-primary rollovers (SV Non-Prim and MV Non-Prim) involving no more
than one roof inversion is substantially greater than in SV Pure, but that this
disparity diminishes for crashes involving multiple inversions. It can further be
concluded that for a given number of roof inversions, the distribution of
injuries and crash characteristics in SV Pure and SV Prim crashes are
sufficiently similar for these categories to be considered collectively for
purposes of understanding etiologies and developing strategies for prevention.
PMID- 26418469
TI - The Utility of Hybrid SPECT/CT Lung Perfusion Scintigraphy in Pulmonary Embolism
Diagnosis.
AB - BACKGROUND: Pulmonary embolism (PE) is diagnosed either by ventilation/perfusion
(V/Q) scintigraphy or pulmonary CT angiography. One of the imaging methods used
in nuclear medicine is hybrid SPECT/CT scintigraphy. OBJECTIVES: The aim of this
study was to evaluate the utility of SPECT/CT(Q) scintigraphy in the diagnosis of
PE and to compare SPECT/CT(Q) with planar(Q) and SPECT(Q) methods. METHODS: The
study group consisted of 109 consecutive patients suspected of having PE referred
for performing lung scintigraphy. The inclusion criteria were: performance of
perfusion planar, SPECT and SPECT/CT scans; availability of clinical data
covering a 6-month follow-up period, and D-dimer level testing. The number of
eligible patients was 84. PE was reported in patients with at least 1 segmental
or 2 subsegmental perfusion defects without parenchymal abnormalities on CT
scans. PE was excluded when there was a normal perfusion pattern or perfusion
defects were caused by lung parenchymal abnormalities or were not arranged in
accordance with the pulmonary vasculature. RESULTS: Twenty-six patients (31%) had
a final diagnosis of PE. The sensitivity and specificity values of each method
were as follows: planar(Q) 73 and 43%, SPECT(Q) 88 and 47% and SPECT/CT(Q) 100
and 83%. SPECT/CT(Q) yielded a significantly higher diagnostic accuracy than
planar(Q) (p < 0.001) and SPECT(Q) (p < 0.001) scans. CONCLUSIONS: We conclude
that hybrid SPECT/CT(Q) imaging has a high diagnostic efficacy in the diagnosis
of PE. Lung perfusion scintigraphy performed with a hybrid SPECT/CT device has a
significantly higher sensitivity and specificity than scanning performed with the
planar or SPECT technique.
PMID- 26418470
TI - A Meta-Analytic Review of Stand-Alone Interventions to Improve Body Image.
AB - OBJECTIVE: Numerous stand-alone interventions to improve body image have been
developed. The present review used meta-analysis to estimate the effectiveness of
such interventions, and to identify the specific change techniques that lead to
improvement in body image. METHODS: The inclusion criteria were that (a) the
intervention was stand-alone (i.e., solely focused on improving body image), (b)
a control group was used, (c) participants were randomly assigned to conditions,
and (d) at least one pretest and one posttest measure of body image was taken.
Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy
of 48 change techniques used in interventions targeted at body image was
developed; all interventions were coded using this taxonomy. RESULTS: The
literature search identified 62 tests of interventions (N = 3,846). Interventions
produced a small-to-medium improvement in body image (d+ = 0.38), a small-to
medium reduction in beauty ideal internalisation (d+ = -0.37), and a large
reduction in social comparison tendencies (d+ = -0.72). However, the effect size
for body image was inflated by bias both within and across studies, and was
reliable but of small magnitude once corrections for bias were applied. Effect
sizes for the other outcomes were no longer reliable once corrections for bias
were applied. Several features of the sample, intervention, and methodology
moderated intervention effects. Twelve change techniques were associated with
improvements in body image, and three techniques were contra-indicated.
CONCLUSIONS: The findings show that interventions engender only small
improvements in body image, and underline the need for large-scale, high-quality
trials in this area. The review identifies effective techniques that could be
deployed in future interventions.
PMID- 26418472
TI - Straddle injury with anal sphincter and rectal rupture in a young girl Case
report.
AB - As a result of increasing sport or car accident, straddle injuries in pediatric
age are becoming increasingly frequent. Mild lesions of the external genitalia
and urinary apparatus, are mainly observed in blunt trauma, whereas more severe
lesions are reported in penetrating injuries; however, ano-rectal involvement
alone, has been reported very rarely and especially in penetrating trauma. We
describe herein a case of straddle trauma occurring in a 14yr old girl involved
in a car accident. The girl reported anal sphincter rupture and rectal wall tear
with a blunt mechanism. No other involvement of genitourinary apparatus was
observed. The diagnostic and surgical approach of this rare consequence of a
straddle, blunt injury are described and commented. KEY WORDS: Anal sphincter
rupture, Emergency laparoscopy, Perineal trauma, Rectal lesion, Straddle injury.
PMID- 26418473
TI - Molecular pathways activation in coronary artery bypass surgery: which role for
pump avoidance?
AB - In this study, we review current knowledge regarding molecular pathways
activation and their possible mechanisms in the perioperative period of coronary
artery bypass surgery (CABG). We also highlight the role of off-pump CABG as a
possible way to better understand these biological changes.We show that, after
both on-pump and off-pump CABG, there is a marked and protracted activation of
several molecular pathways indicating increased inflammatory status, haemostasis
activation, as well as increased oxidative stress and unfavourable endothelial
milieu. These changes persist for days and even weeks after surgery.
Interestingly, a relatively limited number of these pathways show a more
pronounced activation in case of cardiopulmonary bypass use, and these markers
are mainly associated with oxidative stress activation; on the contrary, the vast
majority of the pathways has a similar course both in on and off-pump procedures.
Surgical stress accounts for more protracted and marked molecular pathway
perturbations overall, being the effect of cardiopulmonary, if any, limited to
the very early hours after surgery. The near future of the translational research
in coronary bypass surgery is to develop therapeutic strategies aimed at reducing
this response, that is largely unrelated to cardiopulmonary bypass use, in order
to reduce perioperative complications and to speed up patients' recovery.
PMID- 26418471
TI - Microsphere-based gradient implants for osteochondral regeneration: a long-term
study in sheep.
AB - BACKGROUND: The microfracture technique for cartilage repair has limited ability
to regenerate hyaline cartilage. AIM: The current study made a direct comparison
between microfracture and an osteochondral approach with microsphere-based
gradient plugs. MATERIALS & METHODS: The PLGA-based scaffolds had opposing
gradients of chondroitin sulfate and beta-tricalcium phosphate. A 1-year repair
study in sheep was conducted. RESULTS: The repair tissues in the microfracture
were mostly fibrous and had scattered fissures with degenerative changes.
Cartilage regenerated with the gradient plugs had equal or superior mechanical
properties; had lacunated cells and stable matrix as in hyaline cartilage.
CONCLUSION: This first report of gradient scaffolds in a long-term, large animal,
osteochondral defect demonstrated potential for equal or better cartilage repair
than microfracture.
PMID- 26418474
TI - Cobalt(II) amido complexes derived from a monodentate arylamido ligand featuring
a highly electron-withdrawing C6F5 substituent.
AB - A series of cobalt(ii) complexes of a highly electron-withdrawing amido ligand,
[N(C6F5)(C6H3Pr(i)2-2,6)](-) (L), were synthesized and structurally
characterized. Mononuclear [CoL(Cl)(TMEDA)] (3) and heterobimetallic [CoL2(MU
Cl)Li(THF)3] (4) were obtained by direct metathetical reactions of anhydrous
CoCl2 with one molar equivalent of [LiL(TMEDA)] (1) (TMEDA = Me2NCH2CH2NMe2) and
[LiL(THF)3] (2), respectively. Complex 3 underwent facile ligand substitution
reactions with LiMe and NaN3, yielding the corresponding mixed-ligand complexes
[CoL(X)(TMEDA)] (X = Me 5, N36). Treatment of 3 with NaOMe led to the
heterobimetallic complex [CoL2(MU-OMe)Na(TMEDA)] (7). The solid-state structures
of complexes 1-7 were established by X-ray diffraction analysis.
PMID- 26418475
TI - Toll-like receptors as targets for allergen immunotherapy.
AB - PURPOSE OF REVIEW: Toll-like receptors (TLRs) are novel and promising targets for
allergen immunotherapy. Bench studies suggest that TLR agonists reduce Th2
responses and ameliorate airway hyper-responsiveness. In addition, clinical
trials are at initial phases to evaluate the safety and efficacy of TLR agonists
for the allergen immunotherapy of patients with allergic rhinitis and asthma.
(Figure is included in full-text article.) RECENT FINDINGS: To date, two allergy
vaccine-containing TLR agonists have been investigated in clinical trials;
Pollinex Quattro and AIC. The former contains monophosphoryl lipid, a TLR4
agonist and the latter contains, CpG motifs activating the TLR9 cascade.
Preseasonal subcutaneous injection of both of these allergy vaccines has been
safe and efficacious in control of nasal symptoms of patients with allergic
rhinitis. CRX-675 (a TLR4 agonist), AZD8848 (a TLR7 agonist), VTX-1463 (a TLR8
agonist) and 1018 ISS and QbG10 (TLR9 agonists) are currently in clinical
development for allergic rhinitis and asthma. SUMMARY: TLR agonists herald
promising results for allergen immunotherapy of patients with allergic rhinitis
and asthma. Future research should be directed at utilizing these agents for
immunotherapy of food allergy (for instance, peanut allergy) as well.
PMID- 26418476
TI - Brief Report: Inhibition of miR-145 Enhances Reprogramming of Human Dermal
Fibroblasts to Induced Pluripotent Stem Cells.
AB - MicroRNA (miRNAs) are short noncoding RNA molecules involved in many cellular
processes and shown to play a key role in somatic cell induced reprogramming. We
performed an array based screening to identify candidates that are differentially
expressed between dermal skin fibroblasts (DFs) and induced pluripotent stem
cells (iPSCs). We focused our investigations on miR-145 and showed that this
candidate is highly expressed in DFs relative to iPSCs and significantly
downregulated during reprogramming process. Inhibition of miR-145 in DFs led to
the induction of "cellular plasticity" demonstrated by: (a) alteration of cell
morphology associated with downregulation of mesenchymal and upregulation of
epithelial markers; (b) upregulation of pluripotency-associated genes including
SOX2, KLF4, C-MYC; (c) downregulation of miRNA let-7b known to inhibit
reprogramming; and (iv) increased efficiency of reprogramming to iPSCs in the
presence of reprogramming factors. Together, our results indicate a direct
functional link between miR-145 and molecular pathways underlying reprogramming
of somatic cells to iPSCs.
PMID- 26418477
TI - Topologically Associating Domains: An invariant framework or a dynamic scaffold?
AB - Metazoan genomes are organized into regions of topologically associating domains
(TADs). TADs are demarcated by border elements, which are enriched for active
genes and high occupancy architectural protein binding sites. We recently
demonstrated that 3D chromatin architecture is dynamic in response to heat shock,
a physiological stress that downregulates transcription and causes a global
redistribution of architectural proteins. We utilized a quantitative measure of
border strength after heat shock, transcriptional inhibition, and architectural
protein knockdown to demonstrate that changes in both transcription and
architectural protein occupancy contribute to heat shock-induced TAD dynamics.
Notably, architectural proteins appear to play a more important role in altering
3D chromatin architecture. Here, we discuss the implications of our findings on
previous studies evaluating the dynamics of TAD structure during cellular
differentiation. We propose that the subset of variable TADs observed after
differentiation are representative of cell-type specific gene expression and are
biologically significant.
PMID- 26418478
TI - Surrogate endpoints for clinical trials in primary sclerosing cholangitis: Review
and results from an International PSC Study Group consensus process.
AB - Primary sclerosing cholangitis (PSC) is a rare, but serious, cholestatic disease
for which, to date, no effective therapy exists to halt disease progression
toward end-stage liver disease. Clinical trial design to study drugs that improve
prognosis is hampered by the relatively low event rate of clinically relevant
endpoints. To overcome this shortcoming, there is an urgent need to identify
appropriate surrogate endpoints. At present, there are no established surrogate
endpoints. This article provides a critical review and describes the results of a
consensus process initiated by the International PSC Study Group to delineate
appropriate candidate surrogate endpoints at present for clinical trials in this
frequently dismal disease. The consensus process resulted in a shortlist of five
candidates as surrogate endpoints for measuring disease progression: alkaline
phosphatase (ALP); transient elastography (TE); histology; combination of
ALP+histology; and bilirubin. Of these, histology, ALP, and TE came out as the
most promising. However, the expert panel concluded that no biomarker currently
exceeds level 3 validation. Combining multiple endpoints is advisable.
CONCLUSION: At present, there are insufficient data to support level 2 validation
for any surrogate endpoint in PSC. Concerted efforts by all stakeholders are
highly needed. Novel, promising noninvasive biomarkers are under study and should
be incorporated as exploratory endpoints in clinical trials.
PMID- 26418479
TI - Update on medical and regulatory issues pertaining to compounded and FDA-approved
drugs, including hormone therapy.
AB - OBJECTIVE: We review the historical regulation of drug compounding, concerns
about widespread use of non-Food and Drug Admiistration (FDA)-approved compounded
bioidentical hormone therapies (CBHTs), which do not have proper labeling and
warnings, and anticipated impact of the 2013 Drug Quality and Security Act (DQSA)
on compounding. METHODS: US government websites were searched for documents
concerning drug compounding regulation and oversight from 1938 (passage of
Federal Food, Drug, and Cosmetic Act [FDCA]) through 2014, including
chronologies, Congressional testimony, FDA guidelines and enforcements, and
reports. The FDCA and DQSA were reviewed. PubMed and Google were searched for
articles on compounded drugs, including CBHT. RESULTS: Congress explicitly
granted the FDA limited oversight of compounded drugs in a 1997 amendment to the
FDCA, but the FDA has encountered obstacles in exercising that authority. After
64 patient deaths and 750 adversely affected patients from the 2012 meningitis
outbreak due to contaminated compounded steroid injections, Congress passed the
DQSA, authorizing the FDA to create a voluntary registration for facilities that
manufacture and distribute sterile compounded drugs in bulk and reinforcing FDCA
regulations for traditional compounding. Given history and current environment,
concerns remain about CBHT product regulation and their lack of safety and
efficacy data. CONCLUSIONS: The DQSA and its reinforcement of S503A of the FDCA
solidifies FDA authority to enforce FDCA provisions against compounders of CBHT.
The new law may improve compliance and accreditation by the compounding industry;
support state and FDA oversight; and prevent the distribution of misbranded,
adulterated, or inconsistently compounded medications, and false and misleading
claims, thus reducing public health risk.
PMID- 26418480
TI - Impact of Rett Syndrome Mutations on MeCP2 MBD Stability.
AB - Rett syndrome causing missense mutations in the methyl-CpG-binding domain (MBD)
of methyl CpG-binding protein 2 (MeCP2) were investigated both in silico and in
vitro to reveal their effect on protein stability. It is demonstrated that the
vast majority of frequently occurring mutations in the human population indeed
alter the MBD folding free energy by a fraction of a kcal/mol up to more than 1
kcal/mol. While the absolute magnitude of the change of the free energy is small,
the effect on the MBD functionality may be substantial since the folding free
energy of MBD is about 2 kcal/mol only. Thus, it is emphasized that the effect of
mutations on protein integrity should be evaluated with respect to the wild-type
folding free energy but not with the absolute value of the folding free energy
change. Furthermore, it was observed that the magnitude of the effect is
correlated neither with the burial of the mutation sites nor with the basic amino
acid physicochemical property change. Mutations that strongly perturb the
immediate structural features were found to have little effect on folding free
energy, while very conservative mutations resulted in large changes of the MBD
stability. This observation was attributed to the protein's ability to
structurally relax and reorganize to reduce the effect of mutation. Comparison
between in silico and in vitro results indicated that some Web servers perform
relatively well, while the free energy perturbation approach frequently
overpredicts the magnitude of the free energy change especially when a charged
amino acid is involved.
PMID- 26418481
TI - Association between trabecular bone score and risk factors for fractures in
Korean female patients with rheumatoid arthritis.
AB - OBJECTIVE: To identify the association between trabecular bone score (TBS) and
other known risk factors for fractures in rheumatoid arthritis (RA) patients.
METHODS: One hundred female RA patients aged >=50 years were enrolled. The
following risk factors for fracture were selected: prevalent vertebral fracture
(VF), bone mineral density (BMD), TBS, and 10-year probability of major
osteoporotic fracture by FRAX(r) (MOF-FRAX scores). The associations between risk
factors were identified, and accuracy of TBS, BMD, and FRAX scores to detect the
prevalent VF, the strongest risk factor for future fracture, were assessed.
RESULTS: Twenty-six patients were revealed to have moderate to severe VFs. There
was a modest negative correlation between MOF-FRAX score and TBS (r = -0.367, p
< 0.01), while there was no correlation between MOF-FRAX score and L-spine BMD (r
= -0.050, p = 0.62). The areas under curves (AUCs) were 0.818, 0.683, and 0.518
for the MOF-FRAX score, TBS, and L-spine BMD, respectively. Among patients with
glucocorticoids (GC) use (n = 57), AUCs were 0.762, 0.758, and 0.448 for their
MOF-FRAX score, TBS, and L-spine BMD, respectively. CONCLUSIONS: TBS showed
better correlation with MOF-FRAX score than BMD, and it was superior to BMD in
identifying prevalent VFs in RA patients, especially who are in use of GCs.
PMID- 26418482
TI - Effects of Ambient Air and Temperature on Ionic Gel Gated Single-Walled Carbon
Nanotube Thin-Film Transistor and Circuits.
AB - Single-walled carbon nanotube thin-film transistor (SWCNT TFT) and circuits were
fabricated by fully inkjet printing gold nanoparticles as source/drain
electrodes, semiconducting SWCNT thin films as channel materials, PS-PMMA-PS/EMIM
TFSI composite gel as gate dielectrics, and PEDOT/PSS as gate electrodes. The
ionic gel gated SWCNT TFT shows reversible conversion from p-type transistor
behavior in air to ambipolar features under vacuum due to reversible oxygen
doping in semiconducting SWCNT thin films. The threshold voltages of ionic gel
gated SWCNT TFT and inverters are largely shifted to the low value (0.5 V for p
region and 1.0 V for n-region) by vacuum annealing at 140 degrees C to
exhausively remove water that is incorporated in the ionic gel as floating gates.
The vacuum annealed ionic gel gated SWCNT TFT shows linear temperature dependent
transconductances and threshold voltages for both p- and n-regions. The strong
temperature dependent transconductances (0.08 MUS/K for p-region, 0.4 MUS/K for n
region) indicate their potential application in thermal sensors. In the other
hand, the weak temperature dependent threshold voltages (-1.5 mV/K for p-region,
1.1 mV/K for n-region) reflect their excellent thermal stability.
PMID- 26418483
TI - Hole spin relaxation in InAs/GaAs quantum dot molecules.
AB - We calculate the spin-orbit induced hole spin relaxation between Zeeman sublevels
of vertically stacked InAs quantum dots. The widely used Luttinger-Kohn
Hamiltonian, which considers coupling of heavy- and light-holes, reveals that
hole spin lifetimes (T1) of molecular states significantly exceed those of single
quantum dot states. However, this effect can be overcome when cubic Dresselhaus
spin-orbit interaction is strong. Misalignment of the dots along the stacking
direction is also found to be an important source of spin relaxation.
PMID- 26418484
TI - Force-Field Based Quasi-Chemical Method for Rapid Evaluation of Binary Phase
Diagrams.
AB - We present the Pair Configurations to Molecular Activity Coefficients (PAC-MAC)
method. The method is based on the pair sampling technique of Blanco (Fan, C. F.;
Olafson, B. D.; Blanco, M.; Hsu, S. L. Application of Molecular Simulation to
Derive Phase Diagrams of Binary Mixtures. Macromolecules 1992, 25, 3667-3676)
with an extension that takes the packing of the molecules into account by a free
energy model. The intermolecular energy is calculated using classical force
fields. PAC-MAC is able to predict activity coefficients and corresponding vapor
liquid equilibrium diagrams at least 4 orders of magnitude faster than molecular
simulations. The accuracy of the PAC-MAC method is tested by comparing the
results with experimental data and with the results of the COSMO-SAC model (Lin,
S.-T.; Sandler, S. I. A Priori Phase Equilibrium Prediction from a Segment
Contribution Solvation Model. Ind. Eng. Chem. Res. 2002, 41, 899-913). PAC-MAC
(using the OPLS-aa force field) is shown to be comparable in accuracy to COSMO
SAC, at the considerable advantage that PAC-MAC in principle does not require
quantum calculation, provided proper force fields to be available.
PMID- 26418486
TI - Evaluation of mobile smartphones app as a screening tool for environmental noise
monitoring.
AB - Noise is a global occupational and environmental health hazard with considerable
social and physiological impact and, therefore, there is a need for regular
measurements to boost monitoring and regulations of environmental noise levels in
our communities. This necessitates a readily available, inexpensive, and easy to
use noise measuring device. We aimed to test the sensitivity and validity of
mobile "smart" phones for this purpose. This was a comparative analysis of a
cross sectional study done between January 2014 and February 2015. Noise levels
were measured simultaneously at different locations within Abuja Nigeria at day
and night hours in real time environments. A sound level meter (SLM)
(Extech407730 Digital Soundmeter, serial no.: 2310135, calibration no: 91037) and
three smartphones (Samsung Galaxy note3, Nokia S, and Techno Phantom Z running on
Android "Apps" Androidboy1) were used. Statistical calculations were done with
Pearson correlation, T-test and Consistency within American National Standards
Institute acceptable standard errors. Noise level readings for both daytime and
night with the SLM and the mobile phones showed equivalent values. All noise
level meters measured were <100dB. The daytime readings were nearly identical in
six locations and the maximum difference in values between the SLM and Smartphone
instruments was 3db, noted in two locations. Readings in dBA showed strong
correlation (r = 0.9) within acceptable error limits for Type 2 SLM devices and
no significant difference in the values (p = 0.12 & 0.58) for both day and night.
Sensitivity of the instrument yielded 92.9%. The androidboy1 "app" performance in
this study showed a good correlation and comparative high sensitivity to the
Standard SLM (type 2 SLM device). However there is the need for further studies.
PMID- 26418487
TI - Exploration of the Chiral Recognition of Sugar-Based Diindolylmethane Receptors:
Anion and Receptor Structures.
AB - In this study, we have conducted a systematic investigation of the chiral
recognition of carboxylic anions by D-glucuronic acid/diindolylmethane receptors.
We investigate the influence of the anion structure on chiral recognition in the
diindolylmethane/glucuronic acid-based receptor 1 a. We found that presence of an
additional hydrogen-bond donor at the alpha position to the carboxylic function
is essential for effective chiral differentiation in these systems. Furthermore,
we present a synthetic procedure that allows for the synthesis of sugar-decorated
receptors that possess a modified substituent at the anomeric position. Four new
receptors 1 b-e have been synthesized, and their chiral-discrimination ability
toward model carboxylates is studied. The obtained results show that the chiral
recognition of these receptors can be fine-tuned by incorporation of a proper
substituent into the receptor structure.
PMID- 26418485
TI - Discovery of Indoline-2-carboxamide Derivatives as a New Class of Brain-Penetrant
Inhibitors of Trypanosoma brucei.
AB - There is an urgent need for new, brain penetrant small molecules that target the
central nervous system second stage of human African trypanosomiasis (HAT). We
report that a series of novel indoline-2-carboxamides have been identified as
inhibitors of Trypanosoma brucei from screening of a focused protease library
against Trypanosoma brucei brucei in culture. We describe the optimization and
characterization of this series. Potent antiproliferative activity was observed.
The series demonstrated excellent pharmacokinetic properties, full cures in a
stage 1 mouse model of HAT, and a partial cure in a stage 2 mouse model of HAT.
Lack of tolerability prevented delivery of a fully curative regimen in the stage
2 mouse model and thus further progress of this series.
PMID- 26418488
TI - Does the Acute Care Spinal Cord Injury Setting Predict the Occurrence of Pressure
Ulcers at Arrival to Intensive Rehabilitation Centers?
AB - OBJECTIVE: The objective of this study was to evaluate the impact of acute care
in specialized spinal cord injury (SCI) trauma centers on the prevalence of
pressure ulcers (PU) upon arrival at a functional rehabilitation center after a
traumatic SCI. DESIGN: This is a retrospective cohort study among 123 patients
with traumatic SCI referred to intensive functional rehabilitation between
January 1, 2009, and December 31, 2011. Group 1 (n = 90) was referred from a
level 1 specialized SCI trauma center and group 2 (n = 33) was referred from
seven trauma centers not specialized in SCI. RESULTS: The total prevalence of
patients with PU at admission to functional rehabilitation was 33.3% (26.7% in
group 1 and 51.5% in group 2, P = 0.017). There were also more patients with
multiple PU in group 2 (24.2% vs. 2.2%, P = 0.0001). A binary logistic regression
showed a significant relationship between the occurrence of PU and the type of
acute care facility as well as the ASIA (American Spinal Injury Association)
Impairment Scale grade. Receiving acute care at the specialized SCI trauma center
was associated with a decrease in the number of patients developing one and
multiple PU. CONCLUSIONS: These results highlight the importance of specialized
SCI trauma centers in acute care of patients with traumatic SCI in reducing PU at
their admission to functional rehabilitation settings.
PMID- 26418490
TI - Avascular Necrosis of the Femoral Head Masquerading as Iliopsoas Bursitis:
Imaging With Ultrasound and Magnetic Resonance.
PMID- 26418489
TI - Effectiveness of Individualized Home-Based Exercise on Turning and Balance
Performance Among Adults Older than 50 yrs: A Randomized Controlled Trial.
AB - OBJECTIVE: This study evaluated the effectiveness of an individualized home-based
exercise program that included specific turning exercises in improving turning
performance in adults identified as having unsteadiness during turning. DESIGN: A
single-blind (assessors) randomized controlled trial was conducted with 68
community-dwelling Malaysians aged 50 yrs and older, who had abnormal turning
performance (outside of age and sex, normal limits on the Step/Quick Turn Test
[180-degree turn task on the NeuroCom Balance Master with long plate]). The
intervention group received a 16-wk home exercise program that included two
turning exercises, whereas the control group maintained their usual activities.
RESULTS: Significant group * time effects were found using two-way repeated
measures analysis of variance for turning and balance/mobility measures. The
intervention group significantly improved relative to the control group for (1)
sway when turning 180 degrees Step/Quick Turn, F1,65 = 8.070, P = 0.006; (2) time
to perform 180-degree turn Step/Quick Turn, F1,65 = 8.216, P = 0.006; (3) Timed
Up and Go (single task), F1,65 = 6.647, P = 0.012; (4) Timed Up and Go (dual
task), F1,65 = 8.301, P = 0.005; and (5) static stance sway, F1,65 = 10.491, P =
0.002. CONCLUSIONS: An individualized home exercise program that included
specific exercises to improve turning ability was effective in improving turning
performance in adults older than 50 yrs.
PMID- 26418491
TI - Experience of Remotely Receiving and Delivering Resident Didactic Lectures.
PMID- 26418492
TI - Focal Cingulum Injury by Minor and Direct Head Trauma: A Diffusion Tensor
Tractography Study.
PMID- 26418498
TI - Is adding a new class of cones to the retina sufficient to cure color-blindness?
AB - New genetic methods have made it possible to substitute cone pigments in the
retinas of adult nonhuman primates. Doing so influences the animals' visual
abilities, demonstrating that the gene therapy was effective. However, we argue
that no studies conducted so far have unambiguously demonstrated that the
experimental animals have also acquired the ability to make new color
distinctions. Simply put, it has been shown that animals that underwent the gene
treatment can now-in addition to finding a red ball on a grayish background-find
a green ball on a grayish background. However, it has not been shown that the
animals can distinguish a red ball from a green one. For most people, that
essential ability would be the primary reason for wanting to undergo a treatment
for color-blindness in the first place, for instance, because their color
blindness currently prevents them from pursuing a career as a pilot or
firefighter. It is important to point out such possible limitations of gene
therapy for color-blindness to avoid unwarranted expectations in both clinicians
and patients. To explain the origin of our concerns, we simulate how replacing
the pigment of some cones is expected to influence the outcomes on the behavioral
test used so far. The simulations show that this test does not provide conclusive
evidence that the animals acquired the ability to make new chromatic
distinctions. In our view, it is therefore premature to claim that human color
blindness can be cured through gene therapy. We propose a test that would provide
more conclusive evidence of fundamentally altered color vision after gene
therapy.
PMID- 26418499
TI - Differential item functioning analysis of the Vanderbilt Expertise Test for cars.
AB - The Vanderbilt Expertise Test for cars (VETcar) is a test of visual learning for
contemporary car models. We used item response theory to assess the VETcar and in
particular used differential item functioning (DIF) analysis to ask if the test
functions the same way in laboratory versus online settings and for different
groups based on age and gender. An exploratory factor analysis found evidence of
multidimensionality in the VETcar, although a single dimension was deemed
sufficient to capture the recognition ability measured by the test. We selected a
unidimensional three-parameter logistic item response model to examine item
characteristics and subject abilities. The VETcar had satisfactory internal
consistency. A substantial number of items showed DIF at a medium effect size for
test setting and for age group, whereas gender DIF was negligible. Because online
subjects were on average older than those tested in the lab, we focused on the
age groups to conduct a multigroup item response theory analysis. This revealed
that most items on the test favored the younger group. DIF could be more the rule
than the exception when measuring performance with familiar object categories,
therefore posing a challenge for the measurement of either domain-general visual
abilities or category-specific knowledge.
PMID- 26418500
TI - Inhibition of Phosphate-Induced Vascular Smooth Muscle Cell Osteo-/Chondrogenic
Signaling and Calcification by Bafilomycin A1 and Methylamine.
AB - BACKGROUND/AIMS: Excessive phosphate concentrations trigger vascular
calcification, an active process promoted by osteoinduction of vascular smooth
muscle cells (VSMCs) with increased expression and activity of transcription
factor RUNX2 (Core-binding factor alpha1, CBFA1), alkaline phosphatase (ALPL),
TGFbeta1, transcription factor NFAT5, and NFAT5-sensitive transcription factor
SOX9. The osteoinductive signaling and vascular calcification of
hyperphosphatemic klotho-hypomorphic mice could be reversed by treatment with
NH4Cl, effects involving decrease of TGFbeta1 and inhibition of NFAT5-dependent
osteoinductive signaling. Known effects of NH4Cl include alkalinization of acidic
cellular compartments. The present study explored whether osteo-/chondrogenic
signaling could be influenced by alkalinization of acidic cellular compartments
following inhibition of the vacuolar H+ ATPase with bafilomycin A1 or following
dissipation of the pH gradient across the membranes of acidic cellular
compartments with methylamine. METHODS: Primary human aortic smooth muscle cells
(HAoSMCs) were treated with high phosphate to trigger osteo-/chondrogenic
signaling and calcification in the absence or presence of bafilomycin A1 or
methylamine. Calcium content was determined using a QuantiChrom Calcium assay,
ALP activity by a colorimetric assay and transcript levels by quantitative RT
PCR. RESULTS: High phosphate increased significantly the calcium deposition,
CBFA1 and ALPL mRNA expression as well as alkaline phosphatase activity in
HAoSMCs, all effects ameliorated by both, bafilomycin A1 and methylamine. High
phosphate further significantly up-regulated the mRNA levels of TGFB1, NFAT5 and
SOX9, effects significantly blunted by additional treatment with bafilomycin A1
or methylamine. Treatment of HAoSMCs with human TGFbeta1 protein or high
phosphate up-regulated NFAT5, SOX9, CBFA1 and ALPL mRNA expression to similarly
high levels which could not be further increased by combined treatment with high
phosphate and TGFbeta1. Bafilomycin A1 failed to reverse the osteo-/chondrogenic
signaling triggered by high phosphate together with TGFbeta1. CONCLUSIONS:
Inhibition of the vacuolar H+ ATPase or dissipation of the pH gradient across the
membranes of acidic cellular compartments both disrupt osteo-/chondrogenic
signaling and calcium deposition in VSMCs, observations supporting the hypothesis
that vascular calcification requires acidic cellular compartments.
PMID- 26418501
TI - Thrombosis of multiple angiolipomas due to acenocumarol treatment.
PMID- 26418502
TI - [PRIER II. The Emilia-Romagna Research and Innovation Programme].
AB - The Emilia-Romagna Programme for Research and Innovation "PRIER" was born in 2005
with the aim of increasing cultural and operational conditions for the
development of clinical research, useful both to the Regional Health Service
(SSR) and to the private sectors of pharmaceutical and biomedical areas. In this
context, the PRIER had from the beginning a double connotation: a space where the
SSR can explore issues related to the development of its own research capacity;
and a context where new possible ways of relating and comparison with the
pharmaceutical and biomedical industry are tested. Over the years the activities
of PRIER were defined by: initiatives to strengthen the system of research in
SSR; development of tools to monitor activities of the research; production of
clinical-organizational recommendations for the governance of innovation. In 2013
a new area of discussion and a common interest have been identified on the
subject of clinical registries. In particular, it wanted to build a path of work
able to identify all the possible critical and relevant points (points to
consider), indispensable, necessary or useful to the construction and use of
clinical registries, taking into account the points of view of all actors
involved. The course began with defining the rules of the game and continued with
workshops that allowed to analyse together the matter. At the end of the second
workshop it was decided to make the work carried out visible: first, not to miss
the opportunity offered by the past but recent discussion; secondly, to
facilitate the discussion both on the issue of registers and to the adopted
methodology, which sees the different actors (public and private ones) to reason
together in a context for once not influenced by necessities of negotiation and
government resources.
PMID- 26418503
TI - [Taxonomy and definition of clinical registries].
AB - In order to assess the needs of knowledge about surveillance and registries in
Italy and to prepare a proposal for the advancement of monitoring and recording
capacity, a working group led by the Italian Association of Epidemiology and
composed by the University of Turin, the Institute of Health and Agenas, carried
out a survey of definitions and approaches used in public health and consulted
the main Italian experts in surveillance and registries. Some of the reflections
developed in this project are presented, to assess to which extent they are
adaptable to the prospects the program PRIER aims to. Different aspects of the
issue are analyzed: from the frame work necessary to identify information needs
and how to improve the ability to measure and types of definitions and taxonomies
of the registers, to the implications of the choices about what to include in
registries on regulation of the instruments and investment priorities for new
registries and surveillance.
PMID- 26418504
TI - [Considerations on limits and profits of registries].
AB - The article collects the summary of the discussion occurred in the setting of
PRIER II, in the session dedicated to the taxonomy of registries. Shown below,
some specific contributions by health professionals working at the regional
departments, which deal with registries, as well as the contribution on the same
subject by specialists working at some pharmaceutical companies. In particular,
after the presentation summarized in the article by prof. Giuseppe Costa1, the
contributions, respectively by a representative of the Emilia-Romagna Region, of
a health and hospital service and by the PRIER II workgroup, are following.
Finally, a collective work with all participants to the working group took place
to focus on all the issues considered to be crucial in defining clinical
registries. At the same discussion table, institutional representatives of the
regulatory national and regional branch were also invited to take into
consideration the points of view of all public and private registry users, in
particular in their benefits, limits and purposes. Going through the discussion
on a specific check list and deepening a number of statements identified by the
working group, a list of key points, essential to characterize each clinical
registry, was produced.
PMID- 26418505
TI - [Health registries: methodological issues].
AB - Health registries and observational studies are different entities, and although
several registries are conceived as observational cohort studies, or provide the
data that are needed for cohort or case-control studies, this is not always true:
many registries have specific aims that imply methodological standards that
differ completely from those of an observational study. Of course, whenever a
Registry is conceived with the aim of conducting an observational study, this
will dictate its methods. The difference between a registry and the simple
assembling and analysis of routine clinical data must be stressed as well: a
registry may require that collection of data from different administrative
sources, or of original data not available elsewhere, and must guarantee the
quality and completeness of the information it contains. It has been repeatedly
suggested that the huge databases of health information that are currently
assembled by most health governing bodies should be exploited directly for
evaluations of appropriateness and effectiveness. This is extremely dangerous,
because the inherent potential biases already affecting all observational studies
may completely undermine their validity if the currently accepted methodological
standards are relaxed. Similarly, the use of observational studies for the
assessment of the effectiveness of health technologies must be considered with
caution.
PMID- 26418506
TI - [Considerations on what we can (and what we should not) ask to registries].
AB - This article presents a summary of the discussion which took place during the
works of PRIER II in the session dedicated to the methodology of registries.
Following a thorough analysis of the possible methods and the limits which deal
with the collection of clinical data through the registries, the different points
of view were compared, perhaps the most relevant, related to this activity. All
this has been done by taking advantage by the possibility to observe aspects from
different points of view. In particular, the exercise considered those who have
to deal with the methodological aspects of the registries as an operator of
public health or as a private operator who creates services for companies. The
final goal, again, was to line up a few essential points accompanied by reasoning
and comments useful to anyone who wants to address the issue of registries from
the methodological point of view.
PMID- 26418507
TI - [Use of data: legal and ethical aspects].
AB - Health care professionals and organizations, in carrying out their activities,
consistently handle information related to identified or identifiable (even
indirectly) natural persons, therefore "personal data". The application of
Legislative Decree 30 June 2003 n. 196--the Code concerning the protection of
personal data--as integrated by the pronunciations of the authority tasked with
the application of such a complex legislation, the Authority for the Protection
of Personal Data, consequently follows. The aforementioned legislation is seldom
fully applied even 12 years after its publication, and even so not properly or
with the adequate level of care. As a consequence, the data processed is often
not adequately safeguarded, and compliance is hindered at an organisational
level: this is particularly true with reference to the state of the art in
medical technology, which is characterized by the utilization of ICT technologies
such as the ones used with clinical registries and the Electronic Health Record.
This chapter shows that, even when processing personal data that is of a
sensitive nature, and at the same time of great importance, it is possible to
reconcile the need to access and manage information with the protection of the
individuals to whom such information refers to. This possibility is however
closely linked to the awareness of the issues involved, awareness that in turn
comes from an indispensable knowledge of the different aspects of that complex
legislation.
PMID- 26418509
TI - Free-Standing T-Nb2O5/Graphene Composite Papers with Ultrahigh
Gravimetric/Volumetric Capacitance for Li-Ion Intercalation Pseudocapacitor.
AB - Free-standing electrodes with high gravimetric/volumetric capacitance will open
up potential applications in miniaturized consumer electronics. Herein, we report
a simple synthesis technology of free-standing orthorhombic Nb2O5 (T
Nb2O5)/graphene composite papers for Li-intercalating pseudocapacitive
electrodes. Through a facile polyol-mediated solvothermal reaction, the Nb2O5
nanodots are homogeneously decorated onto the surface of reduced graphite oxide
(rGO), which can form a homogeneous Nb2O5/rGO colloidal suspension that can be
easily fabricated into flexible composite papers. The heat-treated T
Nb2O5/graphene composite papers exhibit a nanoporous layer-stacked structure with
good ionic-electric conductive pathways, high T-Nb2O5 loading of 74.2%, and high
bulk density of 1.55 g cm(-3). Such T-Nb2O5/graphene composite papers show a
superior pseudocapacitor performance as free-standing electrodes, as evidenced by
an ultrahigh gravimetric/volumetric capacitance (620.5 F g(-1) and 961.8 F cm(-3)
at 1 mV s(-1)) and excellent rate capability. Furthermore, an organic electrolyte
based asymmetric supercapacitor is assembled based on T-Nb2O5/graphene composite
papers, which can deliver a high energy density of 47 W h kg(-1) and power
density of 18 kW kg(-1).
PMID- 26418510
TI - Retrieval flexibility and reinstatement in the developing hippocampus.
AB - Episodic memory improves during childhood and this improvement has been
associated with age differences in hippocampal function, but previous research
has not manipulated the possible underlying mechanisms. We tested the hypothesis
that age-related differences in hippocampal activation may reflect changes in
retrieval flexibility. We expected these activation differences to be observed
most prominently in the anterior hippocampus. Functional magnetic resonance
imaging (fMRI) data were collected from children ages 8 and 10, and adults (N =
63) during an associative recognition task that required participants to
recognize pairs of pictures which either appeared in the same location as during
encoding (Same location), or in a flipped location, such that each picture
switched their location with the other member of the pair (Flipped location).
Recognition of same-location pairs placed lower demands on flexible retrieval
compared to recognition of flipped-location pairs. Behaviorally, 8-year-olds
exhibited the strongest correct recognition gains for same-location compared to
flipped-location pairs, and females unexpectedly outperformed males across all
ages. When we examined correct recognition, adults recruited the hippocampal head
more strongly for flipped- versus same-location pairs compared to both groups of
children; in contrast both adults and 10-year-olds recruited the hippocampal tail
more strongly for flipped- versus same-location pairs compared to 8-year-olds.
This pattern was stronger in the left hippocampus and for females. Moreover
hippocampal discrimination between recognized and forgotten items in the same
location condition was stronger in 8-year-olds compared to adults, and was
stronger in the flipped-location condition in adults compared to 8-year-olds;
this pattern was stronger in the left hippocampus. Individual differences in this
discrimination contrast for flipped-location trials in the head and body
predicted performance on an index of creative thinking. Overall, these results
lend new support to the idea that hippocampal development may reflect change in
retrieval flexibility with implications for additional forms of flexible
cognition.
PMID- 26418511
TI - Comprehensive investigation in patients affected by globozoospermia.
PMID- 26418512
TI - Nicotine-Mediated Ca(2+)-Influx Induces IL-8 Secretion in Oral Squamous Cell
Carcinoma Cell.
AB - Cigarette smoking is one of the most important risk factors for the development
of various diseases. Nicotine is the most extensively investigated component of
cigarette smoke, and a comprehensive analysis of the genes induced by nicotine
stimulation revealed that interleukin-8 (IL-8) was induced in oral squamous cell
carcinoma cell (OSCC). Based on this background, the signaling mechanisms of
nicotine-mediated IL-8 induction in OSCC was investigated. Augmented IL-8
secretion by Ca9-22 cells was blocked by the NF-kappaB inhibitor L-1-4'
tosylamino-phenylethyl-chloromethyl ketone (TPCK) and the nicotinic acetylcholine
receptor (nAChR)-specific inhibitor alpha-bungarotoxin (alphaBtx). The downstream
signaling pathway was further examined by pre-incubating the cells with
inhibitors against mitogen-activated protein kinase (MEK), protein kinase C
(PKC), and Ca(2+)/calmodulin-dependent kinase II (CaMK II). Only the CaMK II
inhibitor was found to exert an inhibitory effect on nicotine-mediated IL-8
secretion. Pre-treatment of the Ca9-22 cells with the Ca(2+) chelator BAPTA-AM
drastically inhibited IL-8 secretion. Although nicotine stimulation induced the
phosphorylation of the NF-kappaB p65 subunit, pre-treatment with BAPTA-AM was
found to inhibit this activity significantly. CaMK II-dependent p65
phosphorylation was confirmed by pre-incubation of the cells with CaMK II
inhibitor. The results from this study indicate that the binding of nicotine to
nAChR induces Ca(2+) influx, which results in the activation and phosphorylation
of CaMK II and NF-kappaB p65, respectively. Nicotine-mediated IL-8 induction
should be a trigger for the initiation of various diseases.
PMID- 26418513
TI - Prevalence of erectile dysfunction in a cohort of Italian hypertensive subjects.
AB - The aim of this study was to evaluate the prevalence of erectile dysfunction (ED)
in a cohort of Italian hypertensive men and the association with clinical and
biochemical data. The study involved 270 consecutive hypertensive subjects aged
40-70 years evaluated in Italian Hypertension Centers of six hospitals from
Liguria and Piedmont. ED was assessed through the self-administered questionnaire
of the International Index of Erectile Function. Clinical history with ongoing
drug treatment, various clinical parameters, biochemical data and evidence about
the presence of subclinical target organ damage was collected. Twenty-seven
subjects refused to answer the questionnaire (10%). Among the 243 remained
subjects, 123 presented ED (50.6%). ED was highly related to age, systolic blood
pressure, pulse pressure, smoking status, statin therapy and kidney function. The
addition of a thiazide diuretic to an inhibitor of the renin-angiotensin system
significantly increased the prevalence of ED. The prevalence of ED increased in
relation with the number of hypotensive drug classes taken by the patients. ED
was highly prevalent in this cohort of Italian hypertensive subjects and was
associated with other cardiovascular risk factors, such as age, smoking status
and kidney function. The role of ED as an early marker of cardiovascular disease
is discussed.
PMID- 26418514
TI - Uptake of Pharmaceuticals Influences Plant Development and Affects Nutrient and
Hormone Homeostases.
AB - The detection of a range of active pharmaceutical ingredients (APIs) in the soil
environment has led to a number of publications demonstrating uptake by crops,
however very few studies have explored the potential for impacts on plant
development as a result of API uptake. This study investigated the effect of
carbamazepine and verapamil (0.005-10 mg/kg) on a range of plant responses in
zucchini (Cucurbita pepo). Uptake increased in a dose-dependent manner, with
maximum leaf concentrations of 821.9 and 2.2 mg/kg for carbamazepine and
verapamil, respectively. Increased carbamazepine uptake by zucchini resulted in a
decrease in above (<60%) and below (<30%) ground biomass compared to the controls
(p < 0.05). At soil concentrations >4 mg/kg the mature leaves suffered from burnt
edges and white spots as well as a reduction in photosynthetic pigments but no
such effects were seen for verapamil. For both APIs, further investigations
revealed significant differences in the concentrations of selected plant hormones
(auxins, cytokinins, abscisic acid and jasmonates), and in the nutrient
composition of the leaves in comparison to the controls (p < 0.05). This is some
of the first research to demonstrate that the exposure of plants to APIs is
likely to cause impacts on plant development with unknown implications.
PMID- 26418515
TI - Copper Complex in Poly(vinyl chloride) as a Nitric Oxide-Generating Catalyst for
the Control of Nitrifying Bacterial Biofilms.
AB - In this study, catalytic generation of nitric oxide by a copper(II) complex
embedded within a poly(vinyl chloride) matrix in the presence of nitrite (source
of nitric oxide) and ascorbic acid (reducing agent) was shown to effectively
control the formation and dispersion of nitrifying bacteria biofilms.
Amperometric measurements indicated increased and prolonged generation of nitric
oxide with the addition of the copper complex when compared to that with nitrite
and ascorbic acid alone. The effectiveness of the copper complex-nitrite-ascorbic
acid system for biofilm control was quantified using protein analysis, which
showed enhanced biofilm suppression when the copper complex was used in
comparison to that with nitrite and ascorbic acid treatment alone. Confocal laser
scanning microscopy (CLSM) and LIVE/DEAD staining revealed a reduction in cell
surface coverage without a loss of viability with the copper complex and up to 5
mM of nitrite and ascorbic acid, suggesting that the nitric oxide generated from
the system inhibits proliferation of the cells on surfaces. Induction of nitric
oxide production by the copper complex system also triggered the dispersal of pre
established biofilms. However, the addition of a high concentration of nitrite
and ascorbic acid to a pre-established biofilm induced bacterial membrane damage
and strongly decreased the metabolic activity of planktonic and biofilm cells, as
revealed by CLSM with LIVE/DEAD staining and intracellular adenosine triphosphate
measurements, respectively. This study highlights the utility of the catalytic
generation of nitric oxide for the long-term suppression and removal of
nitrifying bacterial biofilms.
PMID- 26418516
TI - Fast and Noninvasive Characterization of Suspicious Lesions Detected at Breast
Cancer X-Ray Screening: Capability of Diffusion-weighted MR Imaging with MIPs.
AB - PURPOSE: To evaluate the ability of a diagnostic abbreviated magnetic resonance
(MR) imaging protocol consisting of maximum intensity projections (MIPs) from
diffusion-weighted imaging with background suppression (DWIBS) and unenhanced
morphologic sequences to help predict the likelihood of malignancy on suspicious
screening x-ray mammograms, as compared with an abbreviated contrast material
enhanced MR imaging protocol and a full diagnostic breast MR imaging protocol.
MATERIALS AND METHODS: This prospective institutional review board-approved study
included 50 women (mean age, 57.1 years; range, 50-69 years), who gave informed
consent and who had suspicious screening mammograms and an indication for biopsy,
from September 2014 to January 2015. Before biopsy, full diagnostic contrast
enhanced MR imaging was performed that included DWIBS (b = 1500 sec/mm(2)). Two
abbreviated protocols (APs) based on MIPs were evaluated regarding the potential
to exclude malignancy: DWIBS (AP1) and subtraction images from the first
postcontrast and the unenhanced series (AP2). Diagnostic indexes of both methods
were examined by using the McNemar test and were compared with those of the full
diagnostic protocol and histopathologic findings. RESULTS: Twenty-four of 50
participants had a breast carcinoma. With AP1 (DWIBS), the sensitivity was 0.92
(95% confidence interval [CI]: 0.73, 0.98), the specificity was 0.94 (95% CI:
0.77, 0.99), the negative predictive value (NPV) was 0.92 (95% CI: 0.75, 0.99),
and the positive predictive value (PPV) was 0.93 (95% CI: 0.75, 0.99). The mean
reading time was 29.7 seconds (range, 4.9-110.0 seconds) and was less than 3
seconds (range, 1.2-7.6 seconds) in the absence of suspicious findings on the
DWIBS MIPs. With the AP2 protocol, the sensitivity was 0.85 (95% CI: 0.78, 0.95),
the specificity was 0.90 (95% CI: 0.72, 0.97), the NPV was 0.87 (95% CI: 0.69,
0.95), the PPV was 0.89 (95% CI: 0.69, 0.97), and the mean reading time was 29.6
seconds (range, 6.0-100.0 seconds). CONCLUSION: Unenhanced diagnostic MR imaging
(DWIBS mammography), with an NPV of 0.92 and an acquisition time of less than 7
minutes, could help exclude malignancy in women with suspicious x-ray screening
mammograms. The method has the potential to reduce unnecessary invasive
procedures and emotional distress for breast cancer screening participants if it
is used as a complement after the regular screening clarification procedure.
PMID- 26418517
TI - Association of the Number of Years Since Menopause with Metabolic Syndrome and
Insulin Resistance in Chinese Urban Women.
AB - BACKGROUND: This study aimed to assess the prevalence of metabolic syndrome
(MetS) and the association of years since menopause with MetS and Insulin
Resistance (IR) in Chinese women. METHOD: A total of 4436 Chinese subjects aged
40-80 years participated in the study; 790 were premenopausal women, and 3646
were postmenopausal women. IR was arbitrarily defined as a homeostasis model
assessment-IR index (HOMA-IR) value above the 75th percentile of normal glucose
tolerance (NGT). MetS was defined according to the International Diabetes
Federation consensus definition. To test whether there was an association between
the number of years since menopause and MetS, multivariate logistic analysis was
conducted. Premenopausal women were used as a comparison group in regression
analyses. RESULTS: After adjustment for age, body mass index (BMI), and gamma
glutamyltransferase (GGT), more years since menopause was highly associated with
an increased risk of MetS (p for trend <0.05) ; the number of years since
menopause was not correlated with fasting insulin and HOMA-IR. Postmenopausal
women with 10 to 14 years since menopause had the highest risk (odds ratio [OR],
2.10; 95% confidence interval [CI], 1.52-2.89, p < .05) of MetS, high
triglycerides (TG; OR, 1.80; 95% CI, 1.34-2.42, p < .05) and high glucose (OR,
1.52; 95% CI, 1.14-2.05, p < .05) and low high-density lipoprotein cholesterol
(HDL-C; OR, 1.38; 95% CI, 1.18-2.32, p < .05). Postmenopausal women with more
than 15 years since menopause had the highest risk of abdominal obesity (OR,
1.69; 95% CI, 1.05-2.71, p < .05). CONCLUSION: In China, more years since
menopause was highly associated with an increased risk of MetS. Menopausal
history may help identify women with increased risk of developing MetS.
PMID- 26418518
TI - Conicity Index and Waist-to-Hip Ratio Are Superior Obesity Indices in Predicting
10-Year Cardiovascular Risk Among Men and Women.
AB - BACKGROUND: Central obesity has been recognized as a main risk factor for
cardiovascular (CV) events. Three popular central obesity indices are waist
circumference, waist-to-hip ratio (WHR), and waist-to-height ratio; abdominal
volume index and conicity index are 2 recent novel obesity indices. The main aim
of this study is to determine the performance of these indices to best predict 10
year CV events. HYPOTHESIS: Some obesity indices can be used to predict
cardiovascular risk. METHODS: In total, 3199 subjects (age range, 40-79 years)
were enrolled in this cross-sectional study. The American College of
Cardiology/American Heart Association and Framingham risk score tools were used
to estimate the 10-year CV events. Receiver operating characteristic curve
analysis was used to determine the optimal discriminator(s) among the central
obesity measures in the estimation of a 10-year risk of CV events >=7.5%, >=10%,
and >=20% separately. RESULTS: Among the 5 central obesity indices, conicity
index showed the most discriminatory power in estimation of a 10-year CV risk. In
men, based on the American College of Cardiology/American Heart Association tool,
the areas under the curve (AUCs) were from 0.671 to 0.682 based on the 3 above
thresholds, whereas with the Framingham tool, AUCs were from 0.651 to 0.659. In
women, all AUCs were >0.7. Our results also showed WHR to be an almost comparable
discriminator of CV disease risk in the Iranian study population. CONCLUSION:
Conicity index and WHR had a more discriminatory accuracy for 10-year CV events
compared with the other obesity indices.
PMID- 26418520
TI - Design Principles for Heteroatom-Doped Carbon Nanomaterials as Highly Efficient
Catalysts for Fuel Cells and Metal-Air Batteries.
AB - Oxygen reduction reaction/oxygen evolution reaction (ORR/OER) catalytic
activities of p-orbital heteroatom-doped carbon nanomaterials are demonstrated to
correlate to the combination of the electron affinity and electronegativity of
doping elements, which serves as an activity descriptor for the entire family of
p-block element dopants. Such a descriptor has predictive power and enables
effective design of new bifunctional catalysts with enhanced ORR/OER activities.
PMID- 26418519
TI - Chemical composition and cytotoxicity of the essential oil from different parts
of Datura metel L.
AB - The essential oil from different parts of Datura metel L. were extracted using
hydrodistillation and GC-MS was used to analyse the essential oil. The main
components of flowers were ketone (23.61%) and ethyl palmitate (15.84%). The main
components of leaves were ketone (18.84%) and phytol (18.71%). Ketone (39.45%)
and phytol (31.32%) were the major components of petioles. Palmitic acid (30.60%)
and ethyl linoleate (21.56%) were the major components of seeds. The major
ingredient of roots was palmitic acid (52.61%). The main ingredients of the stems
were palmitic acid (38.38%) and ethyl linoleate (17.38%). All the different parts
of essential oil were screened for cytotoxicity. The roots and stems showed the
inhibitory effects against HepG-2 with IC50 levels of 613.88 and 341.12 mg/L. The
leaves and roots showed the inhibitory effects against HeLa with IC50 levels of
267.76 and 348.35 mg/L. All the six parts have inhibitory effects against SGC
7901 cell lines.
PMID- 26418525
TI - Scientific Program of 33rd World Congress of Endourology & SWL Program Book.
PMID- 26418521
TI - Transcriptome Characteristics and X-Chromosome Inactivation Status in Cultured
Rat Pluripotent Stem Cells.
AB - Rat pluripotent stem cells, embryonic stem cells (ESCs), and induced pluripotent
stem cells (iPSCs) as mouse and human ones have a great potential for studying
mammalian early development, disease modeling, and evaluation of regenerative
medicine approaches. However, data on pluripotency realization and self-renewal
maintenance in rat cells are still very limited, and differentiation protocols of
rat ESCs (rESCs) and iPSCs to study development and obtain specific cell types
for biomedical applications are poorly developed. In this study, the RNA-Seq
technique was first used for detailed transcriptome characterization in rat
pluripotent cells. The rESC and iPSC transcriptomes demonstrated a high
similarity and were significantly different from those in differentiated cells.
Additionally, we have shown that reprogramming of rat somatic cells to a
pluripotent state was accompanied by X-chromosome reactivation. There were two
active X chromosomes in XX rESCs and iPSCs, which is one of the key attributes of
the pluripotent state. Differentiation of both rESCs and iPSCs led to X
chromosome inactivation (XCI). The dynamics of XCI in differentiating rat cells
was very similar to that in mice. Two types of facultative heterochromatin
described in various mammalian species were revealed on the rat inactive X
chromosome. To explore XCI dynamics, we established a new monolayer
differentiation protocol for rESCs and iPSCs that may be applied to study
different biological processes and optimized for directed derivation of specific
cell types.
PMID- 26418522
TI - Chlorotoxin: Structure, activity, and potential uses in cancer therapy.
AB - Chlorotoxin is a disulfide-rich stable peptide from the venom of the Israeli
scorpion Leiurus quinquestriatus, which has potential therapeutic applications in
the treatment of cancer. Its ability to preferentially bind to tumor cells has
been harnessed to develop an imaging agent to help visualize tumors during
surgical resection. In addition, chlorotoxin has attracted interest as a vehicle
to deliver anti-cancer drugs specifically to cancer cells. Given its interesting
structural and biological properties, chlorotoxin also has the potential to be
used in a variety of other biotechnology and biomedical applications. Here, we
review the structure, activity and potential applications of chlorotoxin as a
drug design scaffold.
PMID- 26418526
TI - What does end stage in neuromuscular diseases mean? Key approach-based
transitions.
AB - PURPOSE OF REVIEW: To revise the definition of end stage in the setting of
neuromuscular disease (NMD), to understand the implications for the patient,
family and healthcare team, and to address the obstacles involved in the lack of
definition. RECENT FINDINGS: Unlike several conditions such as cancer, kidney or
liver disease, the literature reveals no clear definition or categorization for
NMD. Many articles mention end stage without defining it. Many years ago an
expert consensus panel defined it based on functional criteria (forced vital
capacity values and hypercapnic events). Only for amyotrophic lateral
sclerosis/motoneurone disease has a wider criteria been proposed. As a
consequence, the management of this heterogeneous group of disorders is often
fragmented compared with the well organized palliative care program for cancer
patients. SUMMARY: Better end-stage NMD definitions should help to identify the
goals of care, but a broad range in time and intensity of deterioration make a
valid definition difficult for end-stage NMD. Respiratory care, life-prolonging
therapies, and structured care planning should be seen as complementary rather
than dichotomous. This article emphasized the relevance of an integrated approach
through the whole trajectories of NMD patients considering key transitions.
PMID- 26418527
TI - The contribution of undergraduate palliative care education: does it influence
the clinical patient's care?
AB - PURPOSE OF REVIEW: The aim of this 2-year systematic review is to understand how
learner assessment and curriculum evaluation of education in palliative care is
being undertaken and to examine whether current undergraduate education
influences the clinical patient's care. RECENT FINDINGS: Almost half of the 30
studies reviewed used a qualitative approach to evaluate learning experiences.
Only three of them were controlled studies and a further one was a cohort
study.When students openly express themselves, they agree that there is
'something' deep as regards the core or the essence of medical practice or
nursing. They feel that they become better professionals and better prepared for
the patients, not only in terms of end of life care, but also as regards care,
irrespective of the phase of the disease.The inclusion of palliative care in
undergraduate education is a way of providing knowledge, skill, and competences
about palliative care (especially communication) and also improving attitudes
toward caring in advanced disease and at the end of life. Different methods of
experiential learning, even brief experiences, which bring students into close
contact with palliative care clinical cases or patients, are providing better
results. SUMMARY: From research studies, there is only indirect evidence that
palliative care training at university leads to better clinical care of patients.
In the future, long-term cohort or controlled studies might answer that question.
PMID- 26418528
TI - If you want to understand the invisible, look carefully at the visible.
PMID- 26418529
TI - Early History of Chronic Obstructive Pulmonary Disease 1808-1980.
AB - COPD has become a more popular research area in the last 3 decades, yet the first
clear descriptions of acute and chronic bronchitis were in 1808. This brief
history, comprehensively referenced, leads us through the early developments in
respiratory physiology and their applications. It emphasises the early history of
chronic bronchitis and emphysema in the 19(th) and early 20(th) centuries, long
before the dominant effects of cigarette smoking emerged. This remains relevant
to developing countries today.
PMID- 26418533
TI - Outcomes of patients with intestinal failure after the development and
implementation of a multidisciplinary team.
PMID- 26418531
TI - Aspects of mental health dysfunction among survivors of childhood cancer.
AB - BACKGROUND: Some previous studies have reported that survivors of childhood
cancer are at an increased risk of developing long-term mental health morbidity,
whilst others have reported that this is not the case. Therefore, we analysed 5
year survivors of childhood cancer using the British Childhood Cancer Survivor
Study (BCCSS) to determine the risks of aspects of long-term mental health
dysfunction. PROCEDURE: Within the BCCSS, 10 488 survivors completed a
questionnaire that ascertained mental health-related information via 10 questions
from the Short Form-36 survey. Internal analyses were conducted using
multivariable logistic regression to determine risk factors for mental health
dysfunction. External analyses were undertaken using direct standardisation to
compare mental health dysfunction in survivors with UK norms. RESULTS: This study
has shown that overall, childhood cancer survivors had a significantly higher
prevalence of mental health dysfunction for 6/10 questions analysed compared to
UK norms. Central nervous system (CNS) and bone sarcoma survivors reported the
greatest dysfunction, compared to expected, with significant excess dysfunction
in 10 and 6 questions, respectively; the excess ranged from 4.4-22.3% in CNS
survivors and 6.9-15.9% in bone sarcoma survivors. Compared to expected, excess
mental health dysfunction increased with attained age; this increase was greatest
for reporting 'limitations in social activities due to health', where the excess
rose from 4.5% to 12.8% in those aged 16-24 and 45+, respectively. Within the
internal analyses, higher levels of educational attainment and socio-economic
classification were protective against mental health dysfunction. CONCLUSIONS:
Based upon the findings of this large population-based study, childhood cancer
survivors report significantly higher levels of mental health dysfunction than
those in the general population, where deficits were observed particularly among
CNS and bone sarcoma survivors. Limitations were also observed to increase with
age, and thus it is important to emphasise the need for mental health evaluation
and services across the entire lifespan. There is evidence that low educational
attainment and being unemployed or having never worked adversely impacts long
term mental health. These findings provide an evidence base for risk
stratification and planning interventions.
PMID- 26418534
TI - Pancreatic enzyme supplements are not effective for relieving abdominal pain in
patients with chronic pancreatitis: Meta-analysis and systematic review of
randomized controlled trials.
PMID- 26418532
TI - Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and
Bisperoxidovanadium Complexes.
AB - PTEN is a dual-specificity protein tyrosine phosphatase. As one of the central
tumor suppressors, a thorough regulation of its activity is essential for proper
cellular homeostasis. The precise implications of PTEN inhibition by reactive
oxygen species (e.g. H2 O2 ) and the subsequent structural consequences remain
elusive. To study the effects of PTEN inhibition, bisperoxidovanadium (bpV)
complexes serve as important tools with the potential for the treatment of nerve
injury or cardiac ischemia. However, their mode of action is unknown, hampering
further optimization and preventing therapeutic applications. Based on protein
crystallography, mass spectrometry, and NMR spectroscopy, we elucidate the
molecular basis of PTEN inhibition by H2O2 and bpV complexes. We show that both
molecules inhibit PTEN via oxidative mechanisms resulting in the formation of the
same intramolecular disulfide, therefore enabling the reactivation of PTEN under
reductive conditions.
PMID- 26418535
TI - Domperidone prescribing practices exposed patients to cardiac risk despite a
'black box' warning: A Canadian tertiary care centre study.
PMID- 26418537
TI - PEGylated Silk Nanoparticles for Anticancer Drug Delivery.
AB - Silk has a robust clinical track record and is emerging as a promising biopolymer
for drug delivery, including its use as nanomedicine. However, silk-based
nanomedicines still require further refinements for full exploitation of their
potential; the application of "stealth" design principals is especially necessary
to support their evolution. The aim of this study was to develop and examine the
potential of PEGylated silk nanoparticles as an anticancer drug delivery system.
We first generated B. mori derived silk nanoparticles by driving beta-sheet
assembly (size 104 +/- 1.7 nm, zeta potential -56 +/- 5.6 mV) using
nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the
fabricated silk nanoparticles and verified the aqueous stability and morphology
of the resulting PEGylated silk nanoparticles. We assessed the drug loading and
release behavior of these nanoparticles using clinically established and emerging
anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation
efficiency (>93%) and a pH-dependent release over 14 days. Finally, we
demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied
as single and combination nanomedicines to human breast cancer cells. In
conclusion, these results, taken together with prior silk nanoparticle data,
support a viable future for silk-based nanomedicines.
PMID- 26418536
TI - The Prevalence and Characteristics of Primary Headache and Dream-Enacting
Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi
Centre Cross-Sectional Study.
AB - BACKGROUND: Because the prevalence and characteristics of primary headache have
yet to be thoroughly studied in patients with hypersomnia disorders, including
narcolepsy and idiopathic hypersomnia, we examined these parameters in the
Japanese population. METHODS: In a multicentre cross-sectional survey, among 576
consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35
idiopathic hypersomnia patients were included. Additionally, 61 healthy control
subjects participated. Semi-structured headache questionnaires were administered
to all participants. RESULTS: The patients with narcolepsy (52.9%) and idiopathic
hypersomnia (77.1%) more frequently experienced headache than the healthy
controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for
migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type
headache among the narcolepsy patients, the idiopathic hypersomnia patients and
the control subjects, respectively. Those who experienced migraine more
frequently experienced excessive daytime sleepiness, defined as an Epworth
Sleepiness Scale score of >=10, than those who did not experience headache among
the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic
hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as
evaluated by the rapid eye movement sleep disorders questionnaire, was more
frequently observed in the narcolepsy patients than in the idiopathic hypersomnia
patients and the control subjects. An increased DEB frequency was observed in the
narcolepsy patients with migraines compared to those without headache.
CONCLUSIONS: Migraines were frequently observed in patients with narcolepsy and
idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further
studies are required to assess the factors that contribute to migraines in
narcolepsy and idiopathic hypersomnia patients.
PMID- 26418538
TI - Dual-Energy Computed Tomography-How Accurate Is Gemstone Spectrum Imaging Metal
Artefact Reduction? Its Application to Orthopedic Metal Implants.
AB - OBJECTIVE: To assess the accuracy and suitability of dual-energy computed
tomography (DECT) in scanning metals used in orthopedic implants. MATERIALS AND
METHODS: Four metal phantoms (Cobalt Chrome, Titanium Grade 5, Stainless Steel
316, and Stainless Steel 630), commonly used materials in orthopedic implants,
were scanned by conventional, polychromatic CT as well as Gemstone Spectrum
Imaging (GSI) DECT, with and without metal artefact reduction software (MARS).
Scans were assessed for artefact based on Hounsfield unit values; and surfaces
generated, based on a Canny edge detection algorithm. Two separate metal implants
were also scanned and assessed for dimensional accuracy. RESULTS: Conventional,
polychromatic CT, and GSI DECT (without MARS) scans displayed major beam
hardening in the presence of all four metals. The GSI DECT with MARS showed very
clear and reproducible boundaries with minimal noise surrounding the metal
phantoms. However, geometric analysis found overestimation of the dimensions,
volume, and surface area for most of the metal phantoms. Titanium displayed the
least artefact, compared to the other metals, in all scan scenarios. CONCLUSIONS:
Although metal artefact reduction using GSI DECT looks superior to conventional
CT, when measured objectively, it was shown to overestimate geometries and skew
dimensions. The GSI DECT with MARS should be used with caution, especially when
assessing questions of implant shape or wear.
PMID- 26418539
TI - Superolateral Hoffa's Fat Pad Edema in Collegiate Volleyball Players.
AB - OBJECTIVE: Superolateral Hoffa's fat pad (SHFP) edema is a previously described
magnetic resonance (MR) finding located between the patellar tendon and the
lateral femoral condyle. The purpose of our study was to determine the prevalence
and clinical significance of SHFP edema in female collegiate volleyball players.
MATERIALS AND METHODS: Sixteen female collegiate volleyball players were
consented for bilateral knee evaluations which consisted of history, physical
examination and MR imaging. Each MR study was reviewed for the presence of SHFP
edema, and 6 patellar maltracking measurements were done. These were tibial
tuberosity-trochlear groove distance, patellar translation, lateral
patellofemoral angle, trochlear depth, trochlear sulcus angle, and lateral
trochlear inclination angle. RESULTS: A total of 16 athletes, 32 knees (16 girls;
age range, 18-22 years; mean, 19.9) were enrolled in the study. Sixteen knees
(50%) in 8 athletes had SHFP edema, with 100% bilaterality; 16 knees in 8
athletes had no evidence of SHFP edema (50%). Functional outcomes and physical
examination findings were within normal limits for all athletes with no
difference noted between SHFP edema-positive and -negative individuals. There was
a statistically significant difference in the tibial tuberosity-trochlear groove
distance, patellar translation, and patellofemoral angle (P value of < 0.001,
0.03 and 0.01, respectively) between the SHFP edema-positive and -negative
individuals. CONCLUSIONS: Elite female volleyball athletes have a very high
prevalence of SHFP edema, which is always bilateral. Although the exact etiology
of SHFP edema remains inconclusive, it could potentially be a sensitive indicator
of subtle patellar maltracking which cannot be distinguished by history and
physical examination findings. Given the very high prevalence of SHFP edema and
this being an asymptomatic finding, there is likely little clinical significance
of this in majority of high-performance athletes.
PMID- 26418541
TI - Ossification of the Posterior Longitudinal Ligament: Imaging Findings in the Era
of Cross-Sectional Imaging.
AB - Imaging appearance and classification systems of ossification of the posterior
longitudinal ligament (OPLL) on computed tomography and magnetic resonance
imaging will be reviewed. Computed tomography evaluation most accurately
demonstrates OPLL length and thickness, whereas magnetic resonance imaging has
the advantage of demonstrating abnormal signal in the cord. Neurologic symptoms
are most common in the cervical spine and are related to the degree of spinal
stenosis and presence of cord edema. Surgical treatment usually involves cases of
cervical OPLL and includes anterior or posterior decompression.
PMID- 26418540
TI - Semiquantitative and Quantitative Analyses of Dynamic Contrast-Enhanced Magnetic
Resonance Imaging of Thyroid Nodules.
AB - OBJECTIVE: This study was aimed to determine the utility of quantitative dynamic
contrast-enhanced magnetic resonance imaging (MRI) in differentiating benign and
malignant lesions in patients with known thyroid gland lesions scheduled for
resection. METHODS: Patients scheduled for resection of a thyroid mass were
prospectively enrolled. Dynamic contrast-enhanced MRI scans of the neck were
performed before surgery. After resection, patients were divided into benign and
malignant groups. Quantitative and semiquantitative MRI kinetic measurements of
benign and malignant lesions were compared and analyzed. RESULTS: Twelve benign
and 9 malignant lesions were identified in 19 patients. Mean Ktrans, Ve, and Kep
for benign lesions were 1.69 +/- 1.59 min, 0.44 +/- 0.21 min, and 4.51 +/- 2.96
min, respectively; for the malignant lesions, 0.96 +/- 0.57 min, 0.45 +/- 0.19
min, and 3.57 +/- 3.53 min, respectively (P = 0.1886, 0.8036, and 0.3028,
respectively). Tpeak, ERmax, slopemax, and iAUGC60 for benign lesions were 7.00
+/- 8.09 seconds, 293.27 +/- 141.25 seconds, 76.45 +/- 65.80 seconds, and 63.46
+/- 46.84, respectively; for malignant lesions, 8.11 +/- 8.55 seconds, 227.6 +/-
113.37 seconds, 81.17 +/- 109.71 seconds, and 43.69 +/- 26.19, respectively (P =
0.7525, 0.4941, 0.4474, and 0.3028, respectively). CONCLUSIONS: Dynamic contrast
enhanced MRI pattern of kinetics was not significantly different for benign and
malignant lesions of the thyroid using quantitative or semiquantitative methods.
PMID- 26418542
TI - Pulmonary Leptospirosis With Diffuse Alveolar Hemorrhage: High-Resolution
Computed Tomographic Findings in 16 Patients.
AB - OBJECTIVE: The aim of this study was to evaluate the high-resolution computed
tomographic (HRCT) findings from patients with leptospirosis and diffuse alveolar
hemorrhage (DAH). MATERIALS AND METHODS: We retrospectively reviewed HRCT
findings from 16 patients diagnosed as having leptospirosis causing DAH. The
patient sample was composed of 13 men and 3 women aged 22 to 53 years (mean age,
34.5 years). Diagnosis was established with confirmation of leptospirosis
infection by serologic microagglutination test. Histopathological study was
performed in 8 patients. Two chest radiologists analyzed the HRCT images and
reached decisions by consensus. RESULTS: The predominant HRCT findings were
ground-glass opacities and airspace nodules (both n = 12, 75%), ground-glass
nodules (n = 9, 56.25%), consolidations (n = 7, 43.75%), "crazy-paving" pattern
(n = 3, 18.75%), and interlobular septal thickening without ground-glass opacity
(n = 3, 18.75%). Bilateral pleural effusion was an associated finding in 2
(12.5%) patients. Analysis of the axial distribution of the lesions revealed
diffuse distribution in 11 (68.75%) patients and peripheral lung zone
predominance in 5 (31.25%) patients. Abnormalities were bilateral in all 16
(100%) patients. Analysis of the craniocaudal distribution of the lesions
revealed lower zone predominance in 9 (56.25%) patients, diffuse distribution in
5 (31.25%) patients, middle zone predominance in 1 (6.25%) patient, and upper
zone predominance in 1 (6.25%) patient. CONCLUSIONS: The most frequent HRCT
findings in patients with leptospirosis causing DAH were ground-glass opacities,
airspace nodules, ground-glass nodules, and consolidations. The lesions showed
symmetrical distribution with lower zone predominance in most cases.
PMID- 26418543
TI - The intraabdominal pressure A real indicator of the tension free principle during
anterior wall repair procedure after incisional hernias.
AB - AIM: Incisional hernias represent a late onset complication of any type of
laparotomy, with a relatively high incidence, and reported in 2% to 11% of all
laparotomies. MATERIAL AND METHODS: We performed a prospective longitudinal study
that included a total number of 102 patients. The following parameters were
monitored: patient history clinical findings, time of hospitalization, laboratory
test results, types of surgery. Intra-abdominal pressure variations were measured
using a specialized kit. RESULTS: Obesity was present in 69 of the patients
(67.64%). Mesh plasty was most frequently used (80.39%). The inset of the mesh
was performed in onlay position (40.19%), retromuscular (29.98%) or complete
defect substitution (11.76%). The correlation between the type of abdominal wall
plasty, variations on the Borg dyspnea scal and likewise the correlation between
the VAS (visual analogue scale) pain scale and the abdominal wall plasty
procedures proved to be highly statistically significant: p< 0.001. Furthermore,
the intra-abdominal pressure varied with the type of abdominoplasty carried out,
reviewing the tension free principle. The most important parameter was the intra
abdominal pressure recorded at the end of the abdominoplasty, which showed
significant correlations with the tension free plasties (retromuscular mesh and
substitution mesh). CONCLUSIONS: The tension free methods, reflected by the intra
abdominal pressure variation, were associated with a lower degree of dyspnea, low
postoperative pain and less hospitalization time. KEY WORDS: Borg scale,
Incisional hernia, Intra-abdominal pressure, Onlay, Visual analogue scale.
PMID- 26418544
TI - What is the best imaging modality for diagnosing a large vestibular aqueduct?
PMID- 26418545
TI - Staphylococcus aureus protects its immune-evasion proteins against degradation by
neutrophil serine proteases.
AB - Neutrophils store large quantities of neutrophil serine proteases (NSPs) that
contribute, via multiple mechanisms, to antibacterial immune defences. Even
though neutrophils are indispensable in fighting Staphylococcus aureus
infections, the importance of NSPs in anti-staphylococcal defence is yet unknown.
However, the fact that S. aureus produces three highly specific inhibitors for
NSPs [the extracellular adherence proteins (EAPs) Eap, EapH1 and EapH2], suggests
that these proteases are important for host defences against this bacterium. In
this study we demonstrate that NSPs can inactivate secreted virulence factors of
S. aureus and that EAP proteins function to prevent this degradation.
Specifically, we find that a large group of S. aureus immune-evasion proteins is
vulnerable to proteolytic inactivation by NSPs. In most cases, NSP cleavage leads
to functional inactivation of virulence proteins. Interestingly, proteins with
similar immune-escape functions appeared to have differential cleavage
sensitivity towards NSPs. Using targeted mutagenesis and complementation analyses
in S. aureus, we demonstrate that all EAP proteins can protect other virulence
factors from NSP degradation in complex bacterial supernatants. These findings
show that NSPs inactivate S. aureus virulence factors. Moreover, the protection
by EAP proteins can explain why this antibacterial function of NSPs was masked in
previous studies. Furthermore, our results indicate that therapeutic inactivation
of EAP proteins can help to restore the natural host immune defences against S.
aureus.
PMID- 26418547
TI - (19)F NMR study of ligand dynamics in carboxylate-bridged diiron(II) complexes
supported by a macrocyclic ligand.
AB - A series of asymmetrically carboxylate-bridged diiron(ii) complexes featuring
fluorine atoms as NMR spectroscopic probes, [Fe2(PIM)(Ar(4F-Ph)CO2)2] (10),
[Fe2(F2PIM)(Ar(Tol)CO2)2] (11), and [Fe2(F2PIM)(Ar(4F-Ph)CO2)2] (12), were
prepared and characterized by X-ray crystallography, Mossbauer spectroscopy, and
VT (19)F NMR spectroscopy. These complexes are part of a rare family of syn N
donor diiron(ii) compounds, [Fe2(X2PIM)(RCO2)2], that are structurally very
similar to the active site of the hydroxylase enzyme component of reduced methane
monooxygenase (MMOHred). Solution characterization of these complexes
demonstrates that they undergo intramolecular carboxylate rearrangements, or
carboxylate shifts, a dynamic feature relevant to the reactivity of the diiron
centers in bacterial multicomponent monooxygenases.
PMID- 26418546
TI - In-Depth Duodenal Transcriptome Survey in Chickens with Divergent Feed Efficiency
Using RNA-Seq.
AB - Since the feed cost is a major determinant of profitability in poultry industry,
how to improve feed efficiency through genetic selection is an intriguing subject
for breeders and producers. As a more suitable indicator assessing feed
efficiency, residual feed intake (RFI) is defined as the difference between
observed and expected feed intake based on maintenance and growth. However, the
genetic mechanisms responsible for RFI in chickens are still less well
appreciated. In this study, we investigated the duodenal transcriptome
architecture of extreme RFI phenotypes in the six brown-egg dwarf hens (three per
group) using RNA sequencing technology. Among all mapped reads, an average of
75.62% fell into annotated exons, 5.50% were located in introns, and the
remaining 18.88% were assigned to intergenic regions. In total, we identified 41
promising candidate genes by differential expression analysis between the low and
high RFI groups. Furthermore, qRT-PCR assays were designed for 10 randomly chosen
genes, and nine (90.00%) were successfully validated. Functional annotation
analyses revealed that these significant genes belong to several specific
biological functions related to digestibility, metabolism and biosynthesis
processes as well as energy homeostasis. We also predicted 253 intergenic coding
transcripts, and these transcripts were mainly involved in fundamental biological
regulation and metabolism processes. Our findings provided a pioneering
exploration of biological basis underlying divergent RFI using RNA-Seq, which
pinpoints promising candidate genes of functional relevance, is helpful to guide
future breeding strategies to optimize feed efficiency and assists in improving
the current gene annotation in chickens.
PMID- 26418548
TI - Blast Wave Exposure to the Extremities Causes Endothelial Activation and Damage.
AB - Extremity injury is a significant burden to those injured in explosive incidents
and local ischaemia can result in poor functionality in salvaged limbs. This
study examined whether blast injury to a limb resulted in a change in endothelial
phenotype leading to changes to the surrounding tissue.The hind limbs of
terminally anaesthetized rabbits were subjected to one of four blast exposures
(high, medium, low, or no blast). Blood samples were analyzed for circulating
endothelial cells pre-injury and at 1, 6, and 11 h postinjury as well as analysis
for endothelial activation pre-injury and at 1, 6, and 12 h postinjury. Post
mortem tissue (12 h post-injury) was analysed for both protein and mRNA
expression and also for histopathology. The high blast group had significantly
elevated levels of circulating endothelial cells 6 h postinjury. This group also
had significantly elevated tissue mRNA expression of IL-6, E-selection, TNF
alpha, HIF-1, thrombomodulin, and PDGF. There was a significant correlation
between blast dose and the degree of tissue pathology (hemorrhage, neutrophil
infiltrate, and oedema) with the worst scores in the high blast group. This study
has demonstrated that blast injury can activate the endothelium and in some cases
cause damage that in turn leads to pathological changes in the surrounding
tissue. For the casualty injured by an explosion the damaging effects of
hemorrhage and shock could be exacerbated by blast injury and vice versa so that
even low levels of blast become damaging, all of which could affect tissue
functionality and long-term outcomes.
PMID- 26418551
TI - Correction: Assessing Mitochondrial DNA Variation and Copy Number in Lymphocytes
of ~2,000 Sardinians Using Tailored Sequencing Analysis Tools.
PMID- 26418549
TI - Serum Neurofilament Light Chain Levels Are Associated with Clinical
Characteristics and Outcome in Patients with Cervical Artery Dissection.
AB - BACKGROUND: Serum neurofilament light chain (sNfL) levels represent a promising
marker of neuroaxonal injury. They are elevated in several neurological
conditions, but their importance in cerebrovascular diseases remains unclear. In
a proof of concept study, we compared sNfL levels with clinical characteristics
and outcome in patients with cervical artery dissection (CeAD). METHODS: A total
of 49 non-traumatic CeAD patients were included. sNfL levels were measured by
high-sensitivity electrochemiluminescence immunoassay. Levels were compared with
regard to (i) type of presenting symptoms (local symptoms only (n = 8), transient
ischemic attack (TIA; n = 10) or ischemic stroke (n = 31)), (ii) stroke severity
quantified by National Institute of Health Stroke Scale (NIHSS), (iii) time
interval between onset of symptoms and blood sampling and (iv) 3-month outcome as
measured by the modified Rankin Scale score. Analyses were performed using
univariate and multivariate linear and ordinal regression models. RESULTS: CeAD
patients presenting with stroke had significantly higher sNfL levels (median
108.9 pg/ml, interquartile range (37.8-427.7)) than patients with TIA (16.4 pg/ml
(8.7-36.3), p = 0.002) or local symptoms (23.4 pg/ml (17.8-30.8), p = 0.0007).
Among stroke patients, sNfL levels were positively associated with both NIHSS (p
= 0.0002) and time between stroke onset and serum sampling (p = 1.9 * 10-6).
Higher sNfL levels were associated with unfavorable outcome at 3 months (OR 4.67,
95% CI 1.69-12.95, p = 0.003). However, this association lost significance after
adjustment for NIHSS. The highest sNfL level was observed in a TIA patient who
had ischemic stroke 1 day after serum sampling for sNfL measurement. CONCLUSION:
sNfL levels were increased in CeAD patients presenting with stroke, correlated
with clinical severity and were influenced by the time point of blood sampling.
The prognostic meaning of sNfL in CeAD deserves further testing.
PMID- 26418550
TI - Efficient Driving of Piezoelectric Transducers Using a Biaxial Driving Technique.
AB - Efficient driving of piezoelectric materials is desirable when operating
transducers for biomedical applications such as high intensity focused ultrasound
(HIFU) or ultrasound imaging. More efficient operation reduces the electric power
required to produce the desired bioeffect or contrast. Our preliminary work [Cole
et al. Journal of Physics: Condensed Matter. 2014;26(13):135901.] suggested that
driving transducers by applying orthogonal electric fields can significantly
reduce the coercivity that opposes ferroelectric switching. We present here the
experimental validation of this biaxial driving technique using piezoelectric
ceramics typically used in HIFU. A set of narrow-band transducers was fabricated
with two sets of electrodes placed in an orthogonal configuration (following the
propagation and the lateral mode). The geometry of the ceramic was chosen to have
a resonance frequency similar for the propagation and the lateral mode. The
average (+/- s.d.) resonance frequency of the samples was 465.1 (+/- 1.5) kHz.
Experiments were conducted in which each pair of electrodes was driven
independently and measurements of effective acoustic power were obtained using
the radiation force method. The efficiency (acoustic/electric power) of the
biaxial driving method was compared to the results obtained when driving the
ceramic using electrodes placed only in the pole direction. Our results indicate
that the biaxial method increases efficiency from 50% to 125% relative to the
using a single electric field.
PMID- 26418552
TI - Anharmonic Franck-Condon Factors for the X(2)B1 <- X(1)A1 Photoionization of
Ketene.
AB - The X(2)B1 <- X(1)A1 photoelectron spectra of ketene and its doubly deuterated
isotopologue have been computed from correlated vibrational wave functions as
determined from vibrational configuration interaction theory relying on
multidimensional Born-Oppenheimer potential energy surfaces being obtained from
explicitly correlated coupled-cluster calculations. Duschinsky effects were
accounted for in all cases. Excellent agreement with available experimental data
was achieved.
PMID- 26418554
TI - Cerebral oximetry: the standard monitor of the future?
AB - PURPOSE OF REVIEW: There is an increasing interest in the application of near
infrared spectroscopy (NIRS) as a monitoring tool in noncardiac surgery. This
review summarizes the latest developments and current evidence for the use of
NIRS in the noncardiac intraoperative setting. RECENT FINDINGS: Unanticipated
intraoperative physiological disturbances and a substantial interpatient
variability in the limits of cerebral autoregulation, pose our patients at risk
for adverse cerebral outcome, if the brain is not monitored specifically. In
addition to a means to monitor the brain, NIRS has been shown to allow an
estimate of overall organ oxygenation. Preliminary data suggest a relationship
between cerebral desaturation and both neurologic and major organ morbidity.
SUMMARY: NIRS offers noninvasive monitoring of cerebral and overall organ
oxygenation in a wide range of clinical scenarios. There is an increasing
evidence that the optimized cerebral oxygenation is associated with improved
outcomes in both neurologic and major organ morbidity in a variety of surgical
settings.
PMID- 26418553
TI - Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy
Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using
4D Flow MRI.
AB - INTRODUCTION: Right ventricular (RV) function has increasingly being recognized
as an important predictor for morbidity and mortality in patients with pulmonary
arterial hypertension (PAH). The increased RV after-load increase RV work in PAH.
We used time-resolved 3D phase contrast MRI (4D flow MRI) to derive RV kinetic
energy (KE) work density and energy loss in the pulmonary artery (PA) to better
characterize RV work in PAH patients. METHODS: 4D flow and standard cardiac cine
images were obtained in ten functional class I/II patients with PAH and nine
healthy subjects. For each individual, we calculated the RV KE work density and
the amount of viscous dissipation in the PA. RESULTS: PAH patients had
alterations in flow patterns in both the RV and the PA compared to healthy
subjects. PAH subjects had significantly higher RV KE work density than healthy
subjects (94.7+/-33.7 mJ/mL vs. 61.7+/-14.8 mJ/mL, p = 0.007) as well as a much
greater percent PA energy loss (21.1+/-6.4% vs. 2.2+/-1.3%, p = 0.0001)
throughout the cardiac cycle. RV KE work density and percent PA energy loss had
mild and moderate correlations with RV ejection fraction. CONCLUSION: This study
has quantified two kinetic energy metrics to assess RV function using 4D flow. RV
KE work density and PA viscous energy loss not only distinguished healthy
subjects from patients, but also provided distinction amongst PAH patients. These
metrics hold promise as imaging markers for RV function.
PMID- 26418555
TI - Large databases in anaesthesiology.
AB - PURPOSE OF REVIEW: The purpose of this study is to review the current state of
large database research in anaesthesiology and to describe the evolution of the
National Anesthesia Clinical Outcomes Registry (NACOR) in the USA. RECENT
FINDINGS: The Anesthesia Quality Institute of the American Society of
Anesthesiologists was created to develop a national anaesthesia registry for the
USA. NACOR and the companion Anesthesia Incident Reporting System are now 5 years
old and in daily use by hundreds of US practices. The 30 million cases in NACOR
are an emerging source for 'big data' research in anaesthesiology. SUMMARY: The
Information Age is bringing new capabilities for large database research to the
specialty of anaesthesiology, driven by the formation of registries capable of
capturing a large fraction of all cases performed.
PMID- 26418556
TI - Synthesis of Fused Polycyclic Indoles by Bronsted Acid-Catalyzed Intramolecular
Alkylation of Indoles with Alcohols.
AB - An efficient methodology for the synthesis of a series of new fused polyclyclic
indoles has been developed by Bronsted acid-catalyzed intramolecular Friedel
Crafts reactions of properly designed indolyl alcohols.
PMID- 26418557
TI - Research into Policy: A Brief History of Mitochondrial Donation.
PMID- 26418558
TI - Mitigation of copper toxicity by DNA oligomers in green paramecia.
AB - Impact of transition metals which catalyze the generation of reactive oxygen
species (ROS), on activation of cell death signaling in plant cells have been
documented to date. Similarly in green paramecia (Paramecium bursaria), an
aquatic protozoan species harboring symbiotic green algae in the cytoplasm,
toxicities of various metallic ions have been documented. We have recently
examined the effects of double-stranded GC-rich DNA fragments with copper-binding
nature and ROS removal catalytic activity as novel plant cell-protecting agents,
using the suspension-cultured tobacco cells. Here, we show that above DNA
oligomers protect the cells of green paramecia from copper-induced cell death,
suggesting that the phenomenon firstly observed in tobacco cells is not limited
only within higher plants but it could be universally observable in wider range
of organisms.
PMID- 26418559
TI - Monte Carlo Dosimetry of the 60Co BEBIG High Dose Rate for Brachytherapy.
AB - INTRODUCTION: The use of high-dose-rate brachytherapy is currently a widespread
practice worldwide. The most common isotope source is 192Ir, but 60Co is also
becoming available for HDR. One of main advantages of 60Co compared to 192Ir is
the economic and practical benefit because of its longer half-live, which is 5.27
years. Recently, Eckert & Ziegler BEBIG, Germany, introduced a new afterloading
brachytherapy machine (MultiSource(r)); it has the option to use either the 60Co
or 192Ir HDR source. The source for the Monte Carlo calculations is the new 60Co
source (model Co0.A86), which is referred to as the new BEBIG 60Co HDR source and
is a modified version of the 60Co source (model GK60M21), which is also from
BEBIG. OBJECTIVE AND METHODS: The purpose of this work is to obtain the dosimetry
parameters in accordance with the AAPM TG-43U1 formalism with Monte Carlo
calculations regarding the BEBIG 60Co high-dose-rate brachytherapy to investigate
the required treatment-planning parameters. The geometric design and material
details of the source was provided by the manufacturer and was used to define the
Monte Carlo geometry. To validate the source geometry, a few dosimetry parameters
had to be calculated according to the AAPM TG-43U1 formalism. The dosimetry
studies included the calculation of the air kerma strength Sk, collision kerma in
water along the transverse axis with an unbounded phantom, dose rate constant and
radial dose function. The Monte Carlo code system that was used was EGSnrc with a
new cavity code, which is a part of EGS++ that allows calculating the radial dose
function around the source. The spectrum to simulate 60Co was composed of two
photon energies, 1.17 and 1.33 MeV. Only the gamma part of the spectrum was used;
the contribution of the electrons to the dose is negligible because of the full
absorption by the stainless-steel wall around the metallic 60Co. The XCOM photon
cross-section library was used in subsequent simulations, and the photoelectric
effect, pair production, Rayleigh scattering and bound Compton scattering were
included in the simulation. Variance reduction techniques were used to speed up
the calculation and to considerably reduce the computer time. The cut-off energy
was 10 keV for electrons and photons. To obtain the dose rate distributions of
the source in an unbounded liquid water phantom, the source was immersed at the
center of a cube phantom of 100 cm3. The liquid water density was 0.998 g/cm3,
and photon histories of up to 1010 were used to obtain the results with a
standard deviation of less than 0.5% (k = 1). The obtained dose rate constant for
the BEBIG 60Co source was 1.108+/-0.001 cGyh-1U-1, which is consistent with the
values in the literature. The radial dose functions were compared with the values
of the consensus data set in the literature, and they are consistent with the
published data for this energy range.
PMID- 26418560
TI - The Mechanoreflex and Hemodynamic Response to Passive Leg Movement in Heart
Failure.
AB - BACKGROUND: Sensitization of mechanosensitive afferents, which contribute to the
exercise pressor reflex, has been recognized as a characteristic of patients with
heart failure (HF); however, the hemodynamic implications of this
hypersensitivity are unclear. OBJECTIVES: The present study used passive leg
movement (PLM) and intrathecal injection of fentanyl to blunt the afferent
portion of this reflex arc to better understand the role of the mechanoreflex on
central and peripheral hemodynamics in HF. METHODS: Femoral blood flow (FBF),
mean arterial pressure, femoral vascular conductance, HR, stroke volume, cardiac
output, ventilation, and muscle oxygenation of the vastus lateralis were assessed
in 10 patients with New York Heart Association class II HF at baseline and during
3 min of PLM both with fentanyl and without (control). RESULTS: Fentanyl had no
effect on baseline measures but increased (control vs fentanyl, P < 0.05) the
peak PLM-induced change in FBF (493 +/- 155 vs 804 +/- 198 DeltamL.min(-1)) and
femoral vascular conductance (4.7 +/- 2 vs 8.5 +/- 3 DeltamL.min(-1).mm Hg)(-1)
while norepinephrine spillover (103% +/- 19% vs 58% +/- 17%Delta) and retrograde
FBF (371 +/- 115 vs 260 +/- 68 DeltamL.min(-1)) tended to be reduced (P < 0.10).
In addition, fentanyl administration resulted in greater PLM-induced increases in
muscle oxygenation, suggestive of increased microvascular perfusion. Fentanyl had
no effect on the ventilation, mean arterial pressure, HR, stroke volume, or
cardiac output response to PLM. CONCLUSIONS: Although movement-induced central
hemodynamics were unchanged by afferent blockade, peripheral hemodynamic
responses were significantly enhanced. Thus, in patients with HF, a heightened
mechanoreflex seems to augment peripheral sympathetic vasoconstriction in
response to movement, a phenomenon that may contribute to exercise intolerance in
this population.
PMID- 26418561
TI - Hip Abductor Muscle Weakness in Individuals with Gluteal Tendinopathy.
AB - PURPOSE: This study aimed to compare hip abductor muscle strength between
individuals with symptomatic, unilateral gluteal tendinopathy (GT), and
asymptomatic controls. METHODS: Fifty individuals with GT age between 35 and 70
yr and 50 sex- and age-comparable controls were recruited from the community.
Maximal isometric strength (torque normalized to body mass) of the hip abductors
was recorded in the supine position using an instrumented manual muscle tester. A
two-way mixed ANCOVA, with covariates of self-reported pain during testing and
pain limiting maximum effort, was used to compare hip abductor strength of the
symptomatic and asymptomatic hip between GT and control individuals. Data were
expressed as mean and SD, with the pairwise comparisons expressed as mean
differences and 95% confidence intervals. RESULTS: Individuals with GT
demonstrated significantly lower hip abductor torque of both their symptomatic
and asymptomatic hip than healthy controls (both P < 0.05), with mean strength
deficits of 0.35 N.m.kg (32%) on the symptomatic hip and 0.25 N.m.kg (23%) on the
asymptomatic hip. In individuals with GT, the symptomatic hip was significantly
weaker than the asymptomatic hip with a mean strength deficit of 0.09 N.m.kg
(11%) (P < 0.05). CONCLUSIONS: People with unilateral GT demonstrate significant
weakness of the hip abductor muscles bilaterally when compared with healthy
controls. Although it is not clear whether hip weakness precedes GT or is a
consequence of the condition, the findings provide a basis to consider hip
abductor muscle weakness in the treatment plan for management of GT.
PMID- 26418563
TI - Topsoil and Deep Soil Organic Carbon Concentration and Stability Vary with
Aggregate Size and Vegetation Type in Subtropical China.
AB - The impact of reforestation on soil organic carbon (OC), especially in deep
layer, is poorly understood and deep soil OC stabilization in relation with
aggregation and vegetation type in afforested area is unknown. Here, we collected
topsoil (0-15 cm) and deep soil (30-45 cm) from six paired coniferous forests
(CF) and broad-leaved forests (BF) reforested in the early 1990s in subtropical
China. Soil aggregates were separated by size by dry sieving and OC stability was
measured by closed-jar alkali-absorption in 71 incubation days. Soil OC
concentration and mean weight diameter were higher in BF than CF. The cumulative
carbon mineralization (Cmin, mg CO2-C kg-1 soil) varied with aggregate size in BF
and CF topsoils, and in deep soil, it was higher in larger aggregates than in
smaller aggregates in BF, but not CF. The percentage of soil OC mineralized
(SOCmin, % SOC) was in general higher in larger aggregates than in smaller
aggregates. Meanwhile, SOCmin was greater in CF than in BF at topsoil and deep
soil aggregates. In comparison to topsoil, deep soil aggregates generally
exhibited a lower Cmin, and higher SOCmin. Total nitrogen (N) and the ratio of
carbon to phosphorus (C/P) were generally higher in BF than in CF in topsoil and
deep soil aggregates, while the same trend of N/P was only found in deep soil
aggregates. Moreover, the SOCmin negatively correlated with OC, total N, C/P and
N/P. This work suggests that reforested vegetation type might play an important
role in soil OC storage through internal nutrient cycling. Soil depth and
aggregate size influenced OC stability, and deep soil OC stability could be
altered by vegetation reforested about 20 years.
PMID- 26418564
TI - Direct Synthesis of Nitriles from Aldehydes Using an O-Benzoyl Hydroxylamine
(BHA) as the Nitrogen Source.
AB - The direct synthesis of nitriles from commercially available or easily prepared
aldehydes has been achieved. O-(4-CF3-benzoyl)-hydroxylamine (CF3-BHA) was
utilized as the nitrogen source to generate O-acyl oximes in situ with aldehydes,
which can be converted to a nitrile with the assistance of a Bronsted acid.
Several aliphatic, aromatic, and alpha,beta-unsaturated nitriles that contain
different functional groups were prepared in high yields (up to 94% yield). This
method has notable advantages, such as simple and mild conditions, high yields,
and good functional group tolerance.
PMID- 26418562
TI - Mitochondrial Gene Expression Profiles Are Associated with Maternal Psychosocial
Stress in Pregnancy and Infant Temperament.
AB - BACKGROUND: Gene-environment interactions mediate through the placenta and shape
the fetal brain development. Between the environmental determinants of the fetal
brain, maternal psychosocial stress in pregnancy has been shown to negatively
influence the infant temperament development. This in turn may have adverse
consequences on the infant neurodevelopment extending throughout the entire life
span. However little is known about the underlying biological mechanisms of the
effects of maternal psychosocial stress in pregnancy on infant temperament.
Environmental stressors such as maternal psychosocial stress in pregnancy
activate the stress response cascade that in turn drives the increase in the
cellular energy demand of vital organs with high metabolic rates such as, in
pregnancy, the placenta. Key players of the stress response cascade are the
mitochondria. RESULTS: Here, we tested the expression of all 13 protein-coding
genes encoded by the mitochondria in 108 placenta samples from the Stress in
Pregnancy birth cohort, a study that aims at determining the influence of in
utero exposure to maternal psychosocial stress in pregnancy on infant
temperament. We showed that the expression of the protein-coding mitochondrial
encoded gene MT-ND2 was positively associated with indices of maternal
psychosocial stress in pregnancy including Prenatal Perceived Stress (beta =
0.259; p-regression = 0.004; r2-regression = 0.120), State Anxiety (beta = 0.218;
p-regression = 0.003; r2-regression = 0.153), Trait Anxiety (beta = 0.262; p
regression = 0.003; r2-regression = 0.129) and Pregnancy Anxiety Total (beta =
0.208; p-regression = 0.010; r2-regression = 0.103). In the meantime MT-ND2 was
negatively associated with the infant temperament indices of Activity Level (beta
= -0.257; p-regression = 0.008; r2-regression = 0.165) and Smile and Laughter
(beta = -0.286; p-regression = 0.036; r2-regression = 0.082). Additionally, MT
ND6 was associated with the maternal psychosocial stress in pregnancy index of
Prenatal Perceived Stress (beta = -0.231; p-regression = 0.004; r2-regression =
0.120), while MT-CO2 was associated with the maternal psychosocial stress in
pregnancy indices of State Anxiety (beta = 0.206; p-regression = 0.003; r2
regression = 0.153) and Trait Anxiety (beta = 0.205; p-regression = 0.003; r2
regression = 0.129). CONCLUSIONS: Our data support the role of mitochondria in
responding to maternal psychosocial stress in pregnancy, as assessed in placenta,
while also suggesting an important role for the mitochondria in the infant
temperament development.
PMID- 26418530
TI - The Clots in Legs Or sTockings after Stroke (CLOTS) 3 trial: a randomised
controlled trial to determine whether or not intermittent pneumatic compression
reduces the risk of post-stroke deep vein thrombosis and to estimate its cost
effectiveness.
AB - BACKGROUND: Venous thromboembolism (VTE) is a common cause of death and morbidity
in stroke patients. There are few data concerning the effectiveness of
intermittent pneumatic compression (IPC) in treating patients with stroke.
OBJECTIVES: To establish whether or not the application of IPC to the legs of
immobile stroke patients reduced their risk of deep vein thrombosis (DVT).
DESIGN: Clots in Legs Or sTockings after Stroke (CLOTS) 3 was a multicentre,
parallel-group, randomised controlled trial which allocated patients via a
central randomisation system to IPC or no IPC. A technician blinded to treatment
allocation performed compression duplex ultrasound (CDU) of both legs at 7-10
days and 25-30 days after enrolment. We followed up patients for 6 months to
determine survival and later symptomatic VTE. Patients were analysed according to
their treatment allocation. SETTING: We enrolled 2876 patients in 94 UK hospitals
between 8 December 2008 and 6 September 2012. PARTICIPANTS: INCLUSION CRITERIA:
patients admitted to hospital within 3 days of acute stroke and who were immobile
on the day of admission (day 0) to day 3. EXCLUSION CRITERIA: age < 16 years;
subarachnoid haemorrhage; and contra-indications to IPC including dermatitis, leg
ulcers, severe oedema, severe peripheral vascular disease and congestive cardiac
failure. INTERVENTIONS: Participants were allocated to routine care or routine
care plus IPC for 30 days, or until earlier discharge or walking independently.
MAIN OUTCOME MEASURES: The primary outcome was DVT in popliteal or femoral veins,
detected on a screening CDU, or any symptomatic DVT in the proximal veins,
confirmed by imaging, within 30 days of randomisation. The secondary outcomes
included death, any DVTs, symptomatic DVTs, pulmonary emboli, skin breaks on the
legs, falls with injury or fractures and duration of IPC use occurring within 30
days of randomisation and survival, symptomatic VTE, disability (as measured by
the Oxford Handicap Scale), quality of life (as measured by the European Quality
of Life-5 Dimensions 3 Level questionnaire) and length of initial hospital stay
measured 6 months after randomisation. RESULTS: We allocated 1438 patients to IPC
and 1438 to no IPC. The primary outcome occurred in 122 (8.5%) of 1438 patients
allocated to IPC and 174 (12.1%) of 1438 patients allocated to no IPC, giving an
absolute reduction in risk of 3.6% [95% confidence interval (CI) 1.4% to 5.8%]
and a relative risk reduction of 0.69 (95% CI 0.55 to 0.86). After excluding 323
patients who died prior to any primary outcome and 41 who had no screening CDU,
the primary outcome occurred in 122 of 1267 IPC participants compared with 174 of
1245 no-IPC participants, giving an adjusted odds ratio of 0.65 (95% CI 0.51 to
0.84; p = 0.001). Secondary outcomes in IPC compared with no-IPC participants
were death in the treatment period in 156 (10.8%) versus 189 (13.1%) (p = 0.058);
skin breaks in 44 (3.1%) versus 20 (1.4%) (p = 0.002); and falls with injury in
33 (2.3%) versus 24 (1.7%) (p = 0.221). Among patients treated with IPC, there
was a statistically significant improvement in survival to 6 months (hazard ratio
0.86, 95% CI 0.73 to 0.99; p = 0.042), but no improvement in disability. The
direct cost of preventing a DVT was L1282 per event (95% CI L785 to L3077).
CONCLUSIONS: IPC is an effective and inexpensive method of reducing the risk of
DVT and improving survival in immobile stroke patients. FUTURE RESEARCH: Further
research should test whether or not IPC improves survival in other groups of high
risk hospitalised medical patients. In addition, research into methods to improve
adherence to IPC might increase the benefits of IPC in stroke patients. TRIAL
REGISTRATION: Current Controlled Trials ISRCTN93529999. FUNDING: The start-up
phase of the trial (December 2008-March 2010) was funded by the Chief Scientist
Office of the Scottish Government (reference number CZH/4/417). The main phase of
the trial was funded by the National Institute for Health Research Health
Technology Assessment programme (reference number 08/14/03). Covidien Ltd
(Mansfield, MA, USA) lent its Kendall SCDTM Express sequential compression system
controllers to the 105 centres involved in the trial and donated supplies of its
sleeves. It also provided logistical help in keeping our centres supplied with
sleeves and training materials relevant to the use of their devices. Recruitment
and follow-up were supported by the National Institute for Health Research-funded
UK Stroke Research Network and by the Scottish Stroke Research Network, which was
supported by NHS Research Scotland.
PMID- 26418565
TI - In-Depth Dissection of the P133R Mutation in Steroid 5beta-Reductase (AKR1D1): A
Molecular Basis of Bile Acid Deficiency.
AB - Human steroid-5beta-reductase (aldo-keto reductase 1D1, AKR1D1)
stereospecifically reduces Delta(4)-3-ketosteroids to 5beta-dihydrosteroids and
is essential for steroid hormone metabolism and bile acid biosynthesis. Genetic
defects in AKR1D1 cause bile acid deficiency that leads to life threatening
neonatal hepatitis and cholestasis. The disease-associated P133R mutation caused
significant decreases in catalytic efficiency with both the representative
steroid (cortisone) and the bile acid precursor (7alpha-hydroxycholest-4-en-3
one) substrates. Pro133 is a second shell residue to the steroid binding channel
and is distal to both the cofactor binding site and the catalytic center.
Strikingly, the P133R mutation caused over a 40-fold increase in Kd values for
the NADP(H) cofactors and increased the rate of release of NADP(+) from the
enzyme by 2 orders of magnitude when compared to the wild type enzyme. By
contrast the effect of the mutation on Kd values for steroids were 10-fold or
less. The reduced affinity for the cofactor suggests that the mutant exists
largely in the less stable cofactor-free form in the cell. Using stopped-flow
spectroscopy, a significant reduction in the rate of the chemical step was
observed in multiple turnover reactions catalyzed by the P133R mutant, possibly
due to the altered position of NADPH. Thus, impaired NADPH binding and hydride
transfer is the molecular basis for bile acid deficiency in patients with the
P133R mutation. Results revealed that optimal cofactor binding is vulnerable to
distant structural perturbation, which may apply to other disease-associated
mutations in AKR1D1, all of which occur at conserved residues and are unstable.
PMID- 26418567
TI - Early bone response to machined, sandblasting acid etching (SLA) and novel
surface-functionalization (SLAffinity) titanium implants: characterization,
biomechanical analysis and histological evaluation in pigs.
AB - The purpose of the present study was to examine early tissue response and
osseointegration in the animal model. The surface morphologies of SLAffinity were
characterized using scanning electron microscopy and atomic force microscopy. The
microstructures were examined by X-ray diffraction, and hardness was measured by
nanoindentation. Moreover, the safety and toxicity properties were evaluated
using computer-aided programs and cell cytotoxicity assays. In the animal model,
implants were installed in the mandibular canine-premolar area of 12 miniature
pigs. Each pig received three implants: machine, sandblasted, large grit, acid
etched, and SLAffinity-treated implants. The results showed that surface
treatment did affect bone-to-implant contact (BIC) significantly. At 3 weeks, the
SLAffinity-treated implants were found to present significantly higher BIC values
than the untreated implants. The SLAffinity treatments enhanced osseointegration
significantly, especially at early stages of bone tissue healing. As described
above, the results of the present study demonstrate that the SLAffinity treatment
is a reliable surface modification method.
PMID- 26418566
TI - Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice.
AB - SK2- and KV4.2-containing K+ channels modulate evoked synaptic potentials in CA1
pyramidal neurons. Each is coupled to a distinct Ca2+ source that provides Ca2+
dependent feedback regulation to limit AMPA receptor (AMPAR)- and NMDA receptor
(NMDAR)-mediated postsynaptic depolarization. SK2-containing channels are
activated by Ca2+ entry through NMDARs, whereas KV4.2-containing channel
availability is increased by Ca2+ entry through SNX-482 (SNX) sensitive CaV2.3 R
type Ca2+ channels. Recent studies have challenged the functional coupling
between NMDARs and SK2-containing channels, suggesting that synaptic SK2
containing channels are instead activated by Ca2+ entry through R-type Ca2+
channels. Furthermore, SNX has been implicated to have off target affects, which
would challenge the proposed coupling between R-type Ca2+ channels and KV4.2
containing K+ channels. To reconcile these conflicting results, we evaluated the
effect of SK channel blocker apamin and R-type Ca2+ channel blocker SNX on evoked
excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal neurons from CaV2.3
null mice. The results show that in the absence of CaV2.3 channels, apamin
application still boosted EPSPs. The boosting effect of CaV2.3 channel blockers
on EPSPs observed in neurons from wild type mice was not observed in neurons from
CaV2.3 null mice. These data are consistent with a model in which SK2-containing
channels are functionally coupled to NMDARs and KV4.2-containing channels to
CaV2.3 channels to provide negative feedback regulation of EPSPs in the spines of
CA1 pyramidal neurons.
PMID- 26418569
TI - Strain behavior and lattice dynamics in Ni50Mn35In15.
AB - The lattice dynamics in the polycrystalline shape-memory Heusler alloy
Ni50Mn35In15 have been studied by means of resonant ultrasound spectroscopy
(RUS). RUS spectra were collected in a frequency range 100-1200 kHz between 10
and 350 K. Ni50Mn35In15 exhibits a ferromagnetic transition at 313 K in the
austenite phase and a martensitic transition at 248 K accompanied by a change of
the magnetic state. Furthermore it displays a paramagnetic to ferrimagnetic
transition within the martensitic phase. We determined the temperature dependence
of the shear modulus and the acoustic attenuation of Ni50Mn35In15 and compared it
with magnetization data. Following the structural softening, which accompanies
the martensitic transition as a pretransitional phenomenon, a strong stiffening
of the lattice is observed at the martensitic magneto-structural transition. Only
a weak magnetoelastic coupling is evidenced at the Curie temperatures both in
austenite and martensite phases. The large acoustic damping in the martensitic
phase compared with the austenitic phase reflects the motion of the twin walls,
which freezes out in the low temperature region.
PMID- 26418568
TI - Multiple Cosmic Sources for Meteorite Macromolecules?
AB - The major organic component in carbonaceous meteorites is an organic
macromolecular material. The Murchison macromolecular material comprises aromatic
units connected by aliphatic and heteroatom-containing linkages or occluded
within the wider structure. The macromolecular material source environment
remains elusive. Traditionally, attempts to determine source have strived to
identify a single environment. Here, we apply a highly efficient hydrogenolysis
method to liberate units from the macromolecular material and use mass
spectrometric techniques to determine their chemical structures and individual
stable carbon isotope ratios. We confirm that the macromolecular material
comprises a labile fraction with small aromatic units enriched in (13)C and a
refractory fraction made up of large aromatic units depleted in (13)C. Our
findings suggest that the macromolecular material may be derived from at least
two separate environments. Compound-specific carbon isotope trends for aromatic
compounds with carbon number may reflect mixing of the two sources. The story of
the quantitatively dominant macromolecular material in meteorites appears to be
made up of more than one chapter.
PMID- 26418570
TI - Cost-effectiveness of RAS screening before monoclonal antibodies therapy in
metastatic colorectal cancer based on FIRE3 Study.
AB - The surprising results published by FIRE-3 revealed that the overall survival
(OS) of RAS wild-type metastatic colorectal cancer (mCRC) patients treated with
Cetuximab(Cmab) and FOLFIRI combination was prolonged to 33.1 months. The
substantial increase in testing and treatment costs, however, impose a
considerable health burden on patients and society. Hence the study was aimed to
assess the cost-effectiveness of RAS screening before monoclonal antibodies
(mAbs) therapy based on FIRE-3 study. Four groups were analyzed: group 1,
patients with KRAS testing treated with Cmab and FOLFIRI; group 2, patients with
RAS testing treated with Cmab and FOLFIRI; group 3, patients with KRAS testing
treated with bevacizumab(Bmab) and FOLFIRI; group 4, patients with RAS testing
treated with Bmab and FOLFIRI. A Markov model comprising 3 health states
(progression-free survival, progressive disease and death) was built. The costs
were calculated from a Chinese payer perspective, and survival was reported in
quality-adjusted life-months (QALMs). Average total lifetime costs ranged from
$104,682.44 (RAS-Bmab) to $136,867.44 (RAS-Cmab), while the survival gained
varied from 16.88 QALMs in RAS-Bmab to 21.85 QALMs in RAS-Cmab. The cost per QALM
was $6,263.86 for RAS-Cmab, $6,145.84 for KRAS-Bmab, $6,201.57 for RAS-Bmab and
$6,960.70 for KRAS-Cmab respectively. The KRAS-Cmab strategy was dominated by the
other 3 groups. The first-treatment cost of RAS-Cmab was the most influential one
to the model. In all, the RAS screening prior to Cmab treatment in mCRC seems to
be a cost-effective strategy in the time of monoclonal antibodies (mAbs) therapy
with the most gained QALMs.
PMID- 26418571
TI - RENACER study: Assessment of 12-month efficacy and safety of 168 certolizumab
PEGol rheumatoid arthritis-treated patients from a Spanish multicenter national
database.
AB - OBJECTIVE: To assess effectiveness and safety of certolizumab PEGol (CZP) in
rheumatoid arthritis (RA) patients after 12 months of treatment and to detect
predictors of response. METHODS: Observational longitudinal prospective study of
RA patients from 35 sites in Spain. Variables (baseline, 3- and 12-month
assessment): sociodemographics, previous Disease Modifying Anti-Rheumatic Drug
(DMARD) and previous Biological Therapies (BT) use; TJC, SJC, ESR, CRP, DAS28,
SDAI. Response variables: TJC, SJC, CRP, ESR, and steroids dose reductions, EULAR
Moderate/Good Response, SDAI response and remission, DAS28 remission. Safety
variables: discontinuation due to side-effects. Descriptive, comparative and
Logistic regression analyses were performed. RESULTS: We included 168 patients:
79.2% women, mean age 54.5 years (+/-13.2 SD), mean disease duration 7.5 years
(+/-7.3 SD). Mean number of prior DMARD: 1.4 (+/-1.2 SD), mean number of prior BT
was 0.8 (+/-1.1). Mean time on CZP was 9.8 months (+/-3.4 SD). A total of 71.4%
were receiving CZP at 12-month assessment. Baseline predictors of response: lower
prior number DMARD; low number prior BT; higher CRP, ESR, TJC, SJC, DAS28 and
SDAI (p < 0.05) scores. A 25/46.4% Moderate/Good Response, a 20% SDAI remission,
and a 44% DAS28 remission were observed. We observed 48 discontinuations (28.6%),
31 due to partial or complete ineffectiveness, and 17 due to side-effects.
CONCLUSIONS: CZP showed benefit in severe RA patients, with significant reduction
of all effectiveness parameters, despite the high prevalence of previous BT
exposure in our series. We found CRP, ESR, prior DMARD/BT number, TJC, SJC,
DAS28, and SDAI as baseline predictors of response. CZP was mostly well
tolerated.
PMID- 26418573
TI - High-Performance and Omnidirectional Thin-Film Amorphous Silicon Solar Cell
Modules Achieved by 3D Geometry Design.
AB - High-performance thin-film hydrogenated amorphous silicon solar cells are
achieved by combining macroscale 3D tubular substrates and nanoscaled 3D cone
like antireflective films. The tubular geometry delivers a series of advantages
for large-scale deployment of photovoltaics, such as omnidirectional performance,
easier encapsulation, decreased wind resistance, and easy integration with a
second device inside the glass tube.
PMID- 26418572
TI - Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers
with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes
to pi-Allyls.
AB - The first enantioselective carbonyl crotylations through direct use of alkynes as
chiral allylmetal equivalents are described. Chiral ruthenium(II) complexes
modified by Josiphos (SL-J009-1) catalyze the C-C coupling of TIPS-protected
propargyl ether 1a with primary alcohols 2a-2o to form products of carbonyl
siloxy-crotylation 3a-3o, which upon silyl deprotection-reduction deliver 1,4
diols 5a-5o with excellent control of regio-, anti-diastereo-, and
enantioselectivity. Structurally related propargyl ethers 1b and 1c bearing ethyl
and phenyl-substituents engage in diastereo- and enantioselective coupling, as
illustrated in the formation of adducts 5p and 5q, respectively. Selective mono
tosylation of diols 5a, 5c, 5e, 5f, 5k, and 5m is accompanied by spontaneous
cyclization to deliver the trans-2,3-disubstituted furans 6a, 6c, 6e, 6f, 6k, and
6m, respectively. Primary alcohols 2a, 2l, and 2p were converted to the siloxy
crotylation products 3a, 3l, and 3p, which upon silyl deprotection-lactol
oxidation were transformed to the trans-4,5-disubstituted gamma-butyrolactones
7a, 7l, and 7p. The formation of 7p represents a total synthesis of (+)-trans
whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol C-C
couplings, deuterium labeling studies provide clear evidence of a novel 1,2
hydride shift mechanism that converts metal-bound alkynes to pi-allyls in the
absence of intervening allenes.
PMID- 26418575
TI - Water-Centered Interpretation of Intrinsic pPII Propensities of Amino Acid
Residues: In Vitro-Driven Molecular Dynamics Study.
AB - Amino acid residues of unfolded peptides in water sample only a few basins in the
Ramachandran plot, including prominent polyproline II-like (pPII) conformations.
Dynamics of guest residues, X, in GXG peptides in water were recently reported to
be dominated by pPII and beta-strand-like (beta) conformations, resulting in an
enthalpy-entropy compensation at ~300 K. Using molecular dynamics (MD) in
explicit solvent, we here examine pPII and beta conformational ensembles of 15
guest residues in GXG peptides, quantify local orientation of water around their
side chains through novel water orientation plots, and study their hydration and
hydrogen bonding properties. We show that pPII and beta ensembles are
characterized by distinct water orientations: pPII ensembles are associated with
an increased population of water oriented in parallel to the side chain surface
whereas beta ensembles exhibit more heterogeneous water orientations. The
backbone hydration is significantly higher in pPII than in beta ensembles.
Importantly, pPII to beta hydration differences and the solvent accessible
surface area of Cbeta hydrogens both correlate with experimental pPII
propensities. We propose that pPII conformations are stabilized by a local,
hydrogen-bonded clathrate-like water structure and that residue-specific
intrinsic pPII propensities reflect distinct abilities of side chains to template
this water structure.
PMID- 26418574
TI - Efficacy of probiotic treatment with Bifidobacterium longum 536 for induction of
remission in active ulcerative colitis: A randomized, double-blinded, placebo
controlled multicenter trial.
AB - BACKGROUND AND AIM: We conducted a randomized, double-blinded, placebo-controlled
trial to investigate the efficacy of Bifidobacterium longum 536 (BB536)
supplementation for induction of remission in Japanese patients with active
ulcerative colitis (UC). METHODS: Fifty-six patients with mild to moderate UC
were enrolled. Three patients had pancolitis, 36 had left-sided colitis, and 17
had proctitis. Patients were randomly treated with 2-3 * 10(11) freeze-dried
viable BB536 (28 patients) or placebo (28 patients) for 8 weeks. RESULTS: In
total, 63% of patients receiving BB536 showed clinical remission (UC disease
activity index [UCDAI] <=2) at week 8 compared to 52% of those receiving placebo
(P = 0.395). We observed a significant decrease of UCDAI scores (3.8 +/- 0.4 at
baseline to 2.6 +/- 0.4 at week 8) in the BB536 group (P < 0.01), whereas there
was no significant decrease in the placebo group (P = 0.88). There was also a
significant decrease in the Rachmilewitz endoscopic index (EI) and the Mayo
subscore at week 8 in the BB536 group, whereas there was no significant decrease
in the placebo group. A single patient in the BB536 group complained of a mild
side-effect, but no other adverse effects were observed. CONCLUSION:
Supplementation with BB536 was well tolerated and reduced UCDAI scores, EI and
Mayo subscores after 8 weeks in Japanese patients with mild to moderately active
UC.
PMID- 26418577
TI - Evaluation of a passive optical based end of service life indicator (ESLI) for
organic vapor respirator cartridges.
AB - A passive visual end of service life indicator (ESLI) for certain organic vapors
has been attached to the inside wall of an organic vapor respirator cartridge.
The opposite side of the ESLI touches activated carbon inside the cartridge.
During use, organic vapors moving through the cartridge adsorb into both the
carbon and the ESLI. The cartridge body is clear so that when vapor
concentrations meet a certain threshold, the user may observe the progressive
development of an indicator bar down the side of the ESLI. The cartridge is
deemed ready to change when any part of the indicator bar touches a marked end
line. The performance of the ESLI was observed when the cartridge was tested
against a variety of organic vapors, exposure concentrations above the minimum
indication level, humidities, temperatures, flow rates, and mixtures. In all
cases, the ESLI indicated end of service life with more than 10% cartridge
service life remaining (which is a NIOSH test criteria). The results were also
compared to mathematical predictions of cartridge service life.
PMID- 26418576
TI - RNA-Seq Reveals Acute Manganese Exposure Increases Endoplasmic Reticulum Related
and Lipocalin mRNAs in Caenorhabditis elegans.
AB - Manganese (Mn) is an essential nutrient; nonetheless, excessive amounts can
accumulate in brain tissues causing manganism, a severe neurological condition.
Previous studies have suggested oxidative stress, mitochondria dysfunction, and
impaired metabolism pathways as routes for Mn toxicity. Here, we used the
nematode Caenorhabditis elegans to analyze gene expression changes after acute Mn
exposure using RNA-Seq. L1 stage animals were exposed to 50 mM MnCl2 for 30 min
and analyzed at L4. We identified 746 up- and 1828 downregulated genes (FDR
corrected p < 0.05; two-fold change) that included endoplasmic reticulum related
abu and fkb family genes, as well as six of seven lipocalin-related (lpr) family
members. These were also verified by qRT-PCR. RNA interference of lpr-5 showed a
dramatic increase in whole body vulnerability to Mn exposure. Our studies
demonstrate that Mn exposure alters gene transcriptional levels in different cell
stress pathways that may ultimately contribute to its toxic effects.
PMID- 26418578
TI - Gadolinium(III)-Chelated Silica Nanospheres Integrating Chemotherapy and
Photothermal Therapy for Cancer Treatment and Magnetic Resonance Imaging.
AB - The combination of therapy and diagnosis has been emerging as a promising
strategy for cancer treatment. To realize chemotherapy, photothermal therapy, and
magnetic resonance imaging (MRI) in one system, we have synthesized a new
magnetic nanoparticle (Gd@SiO2-DOX/ICG-PDC) integrating doxorubicin (DOX),
indocyanine green (ICG), and gadolinium(III)-chelated silica nanospheres
(Gd@SiO2) with a poly(diallyldimethylammonium chloride) (PDC) coating. PDC
coating serves as a polymer layer to protect from quick release of drugs from the
nanocarriers and increase cellular uptake. The DOX release from Gd@SiO2-DOX/ICG
PDC depends on pH and temperature. The process will be accelerated in the acidic
condition than in a neutral pH 7.4. Meanwhile, upon laser irradiation, the
photothermal effects promote DOX release and improve the therapeutic efficacy
compared to either DOX-loaded Gd@SiO2 or ICG-loaded Gd@SiO2. Moreover, MRI
results show that the Gd@SiO2-PDC nanoparticles are safe T1-type MRI contrast
agents for imaging. The Gd@SiO2-PDC nanoparticles loaded with DOX and ICG can
thus act as a promising theranostic platform for multimodal cancer treatment.
PMID- 26418579
TI - Design, Synthesis, and Conformational Analysis of Proposed beta-Turn Mimics from
Isoxazoline-Cyclopentane Aminols.
AB - Constrained aminols from oxazanorbornene derivatives have the geometrical
features to be used as beta-turn inducers. Four different stereoisomers were
prepared and spectroscopically characterized (MD calculations, NMR-titration and
VT-NMR experiments). Temperature coefficients in DMSO are indicative for the
existence of an intramolecular hydrogen bond. Chirooptical properties revealed a
beta-turn arrangement of all the synthesized compounds, where, depending on the
absolute configuration of the cyclopentane spacer, they can be labeled as left-
or right-handed turns.
PMID- 26418580
TI - Engineered fibroblast growth factor 19 reduces liver injury and resolves
sclerosing cholangitis in Mdr2-deficient mice.
AB - Defects in multidrug resistance 3 gene (MDR3), which encodes the canalicular
phospholipid flippase, cause a wide spectrum of cholangiopathy phenotypes in
humans. Mice deficient in Mdr2 (murine ortholog of MDR3) develop liver diseases
that closely reproduce the biochemical, histological, and clinical features of
human cholangiopathies such as progressive familial intrahepatic cholestasis and
primary sclerosing cholangitis. We hypothesized that modulating bile acid
metabolism by the gut hormone fibroblast growth factor 19 (FGF19) may represent a
novel approach for treating cholangiopathy and comorbidities. We introduced adeno
associated virus carrying the gene for either the endocrine hormone FGF19 or
engineered FGF19 variant M70 to 12-week old Mdr2-deficient mice with fully
established disease. Effects on serum levels of liver enzymes, liver histology,
and bile acid homeostasis were evaluated. FGF19 and M70 rapidly and effectively
reversed liver injury, decreased hepatic inflammation, attenuated biliary
fibrosis, and reduced cholecystolithiasis in Mdr2-deficient mice.
Mechanistically, FGF19 and M70 significantly inhibited hepatic expression of
Cyp7a1 and Cyp27a1, which encode enzymes responsible for the rate-limiting steps
in the classic and alternate bile acid synthetic pathways, thereby reducing the
hepatic bile acid pool and blood levels of bile acids. Importantly, prolonged
exposure to FGF19, but not M70, led to the formation of hepatocellular carcinomas
in the Mdr2-deficient mice. Furthermore, M70 ameliorated the hepatosplenomegaly
and ductular proliferation that are associated with cholangiopathy. CONCLUSION:
These results demonstrate the potential for treating cholangiopathy by safely
harnessing FGF19 biology to suppress bile acid synthesis.
PMID- 26418582
TI - Molecular Mechanism of Wide Photoabsorption Spectral Shifts of Color Variants of
Human Cellular Retinol Binding Protein II.
AB - Color variants of human cellular retinol binding protein II (hCRBPII) created by
protein engineering were recently shown to exhibit anomalously wide
photoabsorption spectral shifts over ~200 nm across the visible region. The
remarkable phenomenon provides a unique opportunity to gain insight into the
molecular basis of the color tuning of retinal binding proteins for understanding
of color vision as well as for engineering of novel color variants of retinal
binding photoreceptor proteins employed in optogenetics. Here, we report a
theoretical investigation of the molecular mechanism underlying the anomalously
wide spectral shifts of the color variants of hCRBPII. Computational modeling of
the color variants with hybrid molecular simulations of free energy geometry
optimization succeeded in reproducing the experimentally observed wide spectral
shifts, and revealed that protein flexibility, through which the active site
structure of the protein and bound water molecules is altered by remote
mutations, plays a significant role in inducing the large spectral shifts.
PMID- 26418581
TI - Global Identification of Protein Post-translational Modifications in a Single
Pass Database Search.
AB - Bottom-up proteomics database search algorithms used for peptide identification
cannot comprehensively identify post-translational modifications (PTMs) in a
single-pass because of high false discovery rates (FDRs). A new approach to
database searching enables global PTM (G-PTM) identification by exclusively
looking for curated PTMs, thereby avoiding the FDR penalty experienced during
conventional variable modification searches. We identified over 2200 unique, high
confidence modified peptides comprising 26 different PTM types in a single-pass
database search.
PMID- 26418583
TI - Coexistence of Fetal Cardiac Malformation and Maternal Drug-Induced Lupus: Is
Lamotrigine Safe?
AB - Lamotrigine (LTG) is a widely used second-generation antiepileptic drug for long
term therapy of epileptic patients. Although LTG monotherapy during pregnancy is
assumed to be relatively safe, teratogenic effects related to LTG has been
reported previously. The presence of fetal malformations and maternal drug
induced lupus erythematosus concurrently in a pregnant women using LTG have not
been reported before. We herein report a term infant with coarctation of aorta
and ventricular septal defect, who was born to a mother treated with LTG for
epilepsy before conception and throughout pregnancy. The mother was diagnosed
with drug-induced lupus erythematosus at the 36th gestational week, and the
symptoms resolved after discontinuation of the drug. Fetal cardiac anomalies
should be searched in mothers who were exposed to LTG during pregnancy.
PMID- 26418584
TI - Living with lipoedema: reviewing different self-management techniques.
AB - At present, there is no proven cure for lipoedema. Nevertheless, much can be done
to help improve symptoms and prevent progression. Many of these improvements can
be achieved by patients using self-management techniques. This article describes
the range of self-management techniques that community nurses can discuss with
patients, including healthy eating, low-impact exercise, compression garments,
self-lymphatic drainage, and counselling.
PMID- 26418585
TI - Using compression hosiery to prevent rebound swelling.
AB - The management of chronic oedema often consists of a programme of compression
bandaging to reduce swelling and improve skin changes and limb shape, followed by
patient self-care management in compression hosiery. Occasionally, patients
experience rebound swelling and require further episodes of bandaging. In such
cases, a thorough assessment of the causes of the rebound swelling should be
carried out so that they can be eliminated. By evidencing three case studies,
this article demonstrates that Haddenham Custom Goldpunkt garments can be useful
in preventing rebound swelling, making it a cost- and resource-effective method
of managing stubborn chronic oedema and lymphoedema.
PMID- 26418586
TI - Lymphoedema nurse.
PMID- 26418589
TI - Chronic Oedema. Moving forward together.
PMID- 26418590
TI - Not letting lymphoedema get the better of me.
PMID- 26418591
TI - Assessing the effect of chronic oedema with associated ulceration.
AB - Chronic oedema is a common problem in the UK and, given the country's ageing
population, the numbers are predicted to rise. In an epidemiological study
carried out in Derby, England, researchers found the prevalence of chronic oedema
to be 3.99 in every 1000 people, with the prevalence increasing to 10.31 in those
aged 65-74 years. Often, patients with untreated chronic oedema will develop an
ulceration that can lead to further costs and hospital admissions. The cost of
treating chronic wounds has been estimated at L2.3 billion-L3.1 billion a year.
It is therefore surprising that given the number of patients living with these
problems, there is still a lack of knowledge and skill among nurses when
assessing patients with chronic oedema and associated ulceration. This article
offers advice for nurses when assessing leg ulcers in patients with chronic
oedema, detailing the visual skin changes most frequently seen in these patients.
The article also discusses some of the treatment options available, briefly
covering the advantages and disadvantages of each option.
PMID- 26418592
TI - Contextual factors determine the use of allocentric information for reaching in a
naturalistic scene.
AB - Numerous studies have demonstrated that humans incorporate allocentric
information when reaching toward visual targets. So far, it is unclear how this
information is integrated into the movement plan when multiple allocentric cues
are available. In this study we investigated whether and how the extent of
spatial changes and the task relevance of allocentric cues influence reach
behavior. To this end, we conducted two experiments where we presented
participants three-dimensional-rendered images of a naturalistic breakfast scene
on a computer screen. The breakfast scene included multiple objects (allocentric
cues) with a subset of objects functioning as potential reach targets (i.e., they
were task-relevant). Participants freely viewed the scene and after a short
delay, the scene reappeared with one object missing (target) and other objects
being shifted left- or rightwards. Afterwards, participants were asked to reach
toward the target position on a gray screen while fixating the screen center. We
found systematic deviations of reach endpoints in the direction of object shifts
which varied with the number of objects shifted, but only if these objects served
as potential reach targets. Our results suggest that the integration of
allocentric information into the reach plan is determined by contextual factors,
in particular by the extent of spatial cue changes and the task-relevance of
allocentric cues.
PMID- 26418594
TI - [Treatment of obsessive-compulsive disorder: drugs, psychotherapy or combined
treatments?].
AB - Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT)
are first-line treatments for obsessive-compulsive disorder (OCD). However,
little is known concerning whether combining both treatments ab initio is more
effective than either monotherapy alone. A review of the available literature,
which is poor, shows that combining ab initio CBT and SRI has not been found to
be clearly superior of either therapy alone, except for patients with severe
depression (who could be treated effectively with pharmacotherapy alone) and for
children and adolescents. Another promising area of research is combined
sequential treatment, that is the addition of CBT in subjects not responding to
SRIs alone. More research is clearly needed in order to achieve a personalized
treatment plan for every OCD patient.
PMID- 26418593
TI - Molecular Characterization of LjABCG1, an ATP-Binding Cassette Protein in Lotus
japonicus.
AB - LjABCG1, a full-size ABCG subfamily of ATP-binding cassette proteins of a model
legume, Lotus japonicus, was reported as a gene highly expressed during the early
stages of nodulation, but have not been characterized in detail. In this study we
showed that the induction of LjABCG1 expression was remarkable by methyl
jasmonate treatment, and reporter gene experiments indicated that LjABCG1 was
strongly expressed in the nodule parenchyma and cell layers adjacent to the root
vascular tissue toward the nodule. LjABCG1 was suggested to be localized at the
plasma membrane based on the fractionation of microsomal membranes as well as
separation via aqueous two-phase partitioning. The physiological functions of
LjABCG1 in symbiosis and pathogenesis were analyzed in homologous and
heterologous systems. LjABCG1 knock-down L. japonicus plants did not show clear
phenotypic differences in nodule formation, and not in defense against
Pseudomonas syringae, either. In contrast, when LjABCG1 was expressed in the
Arabidopsis pdr8-1 mutant, the penetration frequency of Phytophthora infestans, a
potato late blight pathogen, was significantly reduced in LjABCG1/pdr8-1 than in
pdr8-1 plants. This finding indicated that LjABCG1, at least partially,
complemented the phenotype of pdr8 in Arabidopsis, suggesting the multiple roles
of this protein in plant-microbe interactions.
PMID- 26418595
TI - [Early attachement relationships and epigenetic customization].
AB - Recently, new findings in epigenetic science switched the focus from the
observation of physiological intragenomic dynamics to the idea of an
environmental co-construction of phenotypic expression. In psichodynamic field,
objectual relations and attachement theoreticians emphasized the interpersonal
dimension of individual development, focusing the attention on the relational
matrix of self organization. The construction of stable affective-behavioral
traits throughout different parenting styles has actually found a coincidence in
ethological studies, which have explored the epigenetic processes underlying the
relationship between caregiving and HPA stress responsiveness. An adequate
parenting style seems to support affective regulation throughout psychobiological
hidden moderators, which would tend to rebalance the physiological systems
homeostasis; an unconfident attachment style would promote, on the other hand,
the allostatic load rise. Sites of longlife epigenetic susceptibility have also
been identified in humans; although associated with risk of maladaptive
developing in adverse environmental conditions, they seem to confer protection
under favorable conditions. This persisting possibility of reorganization of
stable traits throughout lifetime, which seems to be activated by a relevant
environmental input, grant to significant relationships, and to therapeutical one
as well, an implicit reconditioning potential which could result into the
configuration of new stable affective-behavioral styles.
PMID- 26418596
TI - [Osteoporosis and major depression: open debate on a bidirectional relationship].
AB - Osteoporosis and depression are two chronic diseases that affect large population
groups with great impact on morbidity, mortality and quality of life. Existing
studies of the relationship between depression and osteoporosis have been
heterogeneous in their design and use of diagnostic instruments for depression,
which might have contributed to the different results on the comorbidity of these
two conditions. Moreover, the direction of the causative link is still
controversial and the etiology remains unclear. Definitely, limited data suggest
that osteoporosis may enhance depressive symptoms, while far more studies have
shown that depression adversely affects bone density and increases fracture risk.
Thus the correlation of these diseases is still under research. This review
comments on a plausible causative relationship and underlying mechanisms that
might elucidate the link between two very common diseases. We describe the
possible impact of osteoporosis on moods and the effect of depression on bone
health. In particular, we focus on the role of the hypothalamic-pituitary
adrenocortical and sympathoadrenal axes, of the parathyroid hormone and
cytokines. We also describe the effect of the antidepressant drugs as well as
lifestyles that may explain this effect.
PMID- 26418597
TI - [The onset of affective disorder: impact of duration of untreated psychosis on
global functioning].
AB - AIM: Observational study on a young sample at the onset of affective disorder
seeking help to a dedicated service, with the aim to evaluate the age of onset,
the duration of untreated psychosis (DUP), and the functional outcome at 2-year
follow-up. METHODS: For 57 young people at First Episode Psychosis (FEP) of
Affective Disorder, consecutively recruited to SMILE service, were collected
socio-demographic and clinical (DUP, psychiatric history, age of onset) data and
psychopathological (BPRS e SCL-90), perceived distress (GHQ-12) and functioning
(VGF) evaluations. RESULTS: Two years after the access to SMILE service, the
sample showed a functional improvement, with a duration of untreated psychosis
(DUP) of 120,9 weeks and a mean age of onset of 21 years. More than 50% of the
sample reported a family psychiatric history; this subgroup showed a higher
substance use and a longer DUP compared to young people with a negative family
psychiatric history. DISCUSSION AND CONCLUSIONS: This study confirms the problem
of the diagnostic delay of young people at FEP of Affective Disorder and
underlines the role of family psychiatric history. Our results support the need
of a specialized service to improve the early detection, identification and
treatment of mental disorders.
PMID- 26418598
TI - [Murder of the doctor].
AB - AIM: To examine possible risk factors for the doctor to be killed by the patient
in the clinical practice by examining a series of murders that involved
physicians. METHODS: This aim has been achieved through a retrospective review on
clinical cases of doctors killed by patients within the period between 1988 and
2013, in Italy. RESULTS: In this period 18 Italian doctors have been killed in
the workplace, with a rate of 0.3/100,000. In 7 cases, the murder resulted in the
context of doctor-dissatisfaction; in 7 cases the murder was committed by a
psychiatric patient; 1 case in the context of a stalking; 3 cases occurred in a
workplace which was not safe enough. Four categories of at-risk contexts have
been identified. One category includes a murder in the context of a doctor
dissatisfaction, perceived by patient. The second category concerns murders
committed by patients suffering from mental illness. A third category includes
homicides in a workplace which is not safe. The last category comprises the
murder in the context of stalking. CONCLUSIONS: These categories identify
specific dangerous situations for physicians, in which are highlighted elements
that have played a crucial role in the murder and for which special precautions
are suggested preventive.
PMID- 26418599
TI - ["Socialization in real environment" in the rehabilitative interventions of a
Psychiatric Unit of Lombardia Region: history, methodology, activities, and
critical aspects].
AB - INTRODUCTION: The activities of rehabilitation and social reintegration related
to work placement have been an important component in the rehabilitation
practices of the Psychiatry Unit n. 20 (UOP 20) of the Spedali Civili Hospital of
Brescia because of a deeply rooted culture of industrial work among the
inhabitants of the served area. METHODS: Through the analysis of the
individualized tools and the routines adopted to satisfy the needs for
rehabilitation and risocialization, with reference to the axis "work", of people
followed by the UOP 20, the methods of definition and realization of the paths of
Socialization in Real Environment (SAR) have been developed. RESULTS: A research
conducted over a period of six years highlighted the therapeutic significance of
SAR rehabilitation pathways. We found a general improvement in the quality of
life of patients followed and the possibility of access to real work market for
some of them through the empowerment of individuals and communities and the
constant and long-lasting commitment of service and local communities to the
integration and implementation of resources (both of patients and of life
contexts). DISCUSSION: Local experience is compared with the broader landscape of
the interventions on employment in people with psychiatric disorders to highlight
similarities and differences in order to facilitate the building of a common
language and to promote the continuous improvement of rehabilitative practices
and interventions.
PMID- 26418600
TI - Cerebral perfusional effects of 1-year rivastigmine treatment in Alzheimer
disease: a case report.
AB - It is described the case of a 74-years-old woman with probable Alzheimer Disease
who showed good clinical response to rivastigmine associated with relevant
improvement of cerebral perfusion after 1 year of treatment. The single-photon
emission computed tomography (SPECT) scan showed a significant improvement in
cortical uptake of the tracer in temporo-parietal and frontal regions in
comparison to the examination performed before the treatment.
PMID- 26418601
TI - [In Process Citation].
PMID- 26418602
TI - "Egg-Box"-Assisted Fabrication of Porous Carbon with Small Mesopores for High
Rate Electric Double Layer Capacitors.
AB - Here we report a method to fabricate porous carbon with small mesopores around 2
4 nm by simple activation of charcoals derived from carbonization of seaweed
consisting of microcrystalline domains formed by the "egg-box" model. The
existence of mesopores in charcoals leads to a high specific surface area up to
3270 m(2) g(-1), with 95% surface area provided by small mesopores. This special
pore structure shows high adaptability when used as electrode materials for an
electric double layer capacitor, especially at high charge-discharge rate. The
gravimetric capacitance values of the porous carbon are 425 and 210 F g(-1) and
volumetric capacitance values are 242 and 120 F cm(-3) in 1 M H2SO4 and 1 M TEA
BF4/AN, respectively. The capacitances even remain at 280 F g(-1) (160 F cm(-3))
at 100 A g(-1) and 156 F g(-1) (90 F cm(-3)) at 50 A g(-1) in the aqueous and
organic electrolytes, demonstrating excellent high-rate capacitive performance.
PMID- 26418603
TI - Analysis of Human and Porcine Skin in vivo/ex vivo for Penetration of Selected
Oils by Confocal Raman Microscopy.
AB - BACKGROUND: The subject of oil penetration into the skin is controversially
discussed in the scientific literature. METHODS: Confocal Raman microscopy was
used for analyzing oil penetration into the skin. The following methods were
applied in the study: methods based on tracking specific peaks (method 1), the
nonrestricted multiple least square fit (method 2), analyzing the lipid-to
keratin peak ratio using the perpendicular drop-down cutoff procedure (method 3),
and the Gaussian function-based deconvolution procedure (method 4). RESULTS: The
results obtained using methods 1, 2 and 4 show that the investigated oils do not
penetrate deeper than 11 um into human and porcine skin. Petrolatum has a
prominent swelling effect on the stratum corneum (32% in vivo, 28% ex vivo),
while the other oils exhibit no significant swelling effect. By using method 3,
the penetration profile of oils, and especially of petrolatum, into the skin was
interpreted incorrectly for various reasons that are addressed herein below.
CONCLUSION: Predominantly remaining in the uppermost corneocyte layers of the
stratum corneum, topically applied oils do not reach the viable cells of the
stratum spinosum. To exclude any possible mistakes when using the lipid-keratin
Raman peak (2,820-3,030 cm-1), the penetration analysis should be performed using
the Gaussian function-based deconvolution procedure.
PMID- 26418605
TI - Blood Pressure Characteristics in Moderate to Severe Renal Insufficiency.
AB - BACKGROUND/AIMS: Ambulatory blood pressure monitoring (ABPM) in chronic kidney
disease (CKD) patients has been extensively studied, but few investigations have
attempted to relate ABPM with CKD stages. The objectives of this article were to
compare ABPM parameters for the diagnosis and treatment determination of CKD with
daytime clinic blood pressure (BP) measurements. We also investigated BP and
renal injury in combined hypertension and CKD. We supposed ABPM was important in
combined hypertension and CKD. METHODS: We compared ABPM in hypertension
patients, including 152 patients with combined hypertension and CKD. Patients
with combined hypertension and CKD were grouped according to severity into stages
1 through 3 (Stage 1-3) and stages 4 and 5 (Stage 4-5). RESULTS: In the Stage 4-5
group, systolic BP (SBP) (daytime, nighttime and 24 h mean), diastolic BP (DBP),
pulse pressure and SBP standard deviations (SD) (daytime and 24 h) were higher.
SBP and DBP loads were significantly higher in the Stage 4-5 group. The nighttime
load was higher than the daytime load. Mean arterial pressure (MAP) was higher
and heart rates (HR) were faster in the Stage 4-5 group. CONCLUSIONS: BP load
should be a component employed in ABPM to determine cardiovascular risk
stratification. MAP and HR might be associated with risk to develop end-stage
renal disease.
PMID- 26418606
TI - Memory and navigation: Compression of space varies with route length and turns.
AB - For memory to be efficient and useful during recall, problem-solving, and
planning, retrieval must be compressed in time. Evidence from rodents suggests
that neural compression during replay of spatial memories varies widely, with a
range of compression ratios reported from 6:1 to 64:1. Anecdotal evidence
suggests that similar compression occurs during mental navigation in humans: we
recall how to get from one place to another countless times almost every day of
our lives, and this recall never takes as long as physically travelling those
routes would take. In this experiment we sought to determine whether this
behavioural compression could be measured during mental navigation in humans
(spatial memory replay), and which factors might affect the compression of such
spatial memories. To this end, thirty participants mentally navigated routes
between two landmarks, which varied in length and number of turns, as we measured
replay times and recorded ratings of familiarity, detail, and presence. A multi
level model was used to determine which factors were associated with variation in
compression. Route length and number of turns emerged from this model as
significantly correlated with compression, such that longer routes were more
compressed while compression was attenuated as the number of turns in a route
increased. This suggests that compression during recall may be affected by
specific features of a route, especially those that may act to segment the space
or event being represented.
PMID- 26418612
TI - Isotope Fractionation Associated with the Indirect Photolysis of Substituted
Anilines in Aqueous Solution.
AB - Organic micropollutants containing aniline substructures are susceptible to
different light-induced transformation processes in aquatic environments and
water treatment operations. Here, we investigated the magnitude and variability
of C and N isotope fractionation during the indirect phototransformation of four
para-substituted anilines in aerated aqueous solutions. The model
photosensitizers, namely 9,10-anthraquinone-1,5-disulfonate and methylene blue,
were used as surrogates for dissolved organic matter chromophores generating
excited triplet states in sunlit surface waters. The transformation of aniline, 4
CH3-, 4-OCH3-, and 4-Cl-aniline by excited triplet states of the photosensitizers
was associated with inverse and normal N isotope fractionation, whereas C isotope
fractionation was negligible. The apparent 15N kinetic isotope effects (AKIE)
were almost identical for both photosensitizers, increased from 0.9958+/-0.0013
for 4-OCH3-aniline to 1.0035+/-0.0006 for 4-Cl-aniline, and correlated well with
the electron donating properties of the substituent. N isotope fractionation is
pH-dependent in that H+ exchange reactions dominate below and N atom oxidation
processes above the pKa value of the substituted aniline's conjugate acid.
Correlations of C and N isotope fractionation for indirect phototransformation
were different from those determined previously for the direct photolysis of
chloroanilines and offer new opportunities to distinguish between abiotic
degradation pathways.
PMID- 26418607
TI - Use of an IL1-receptor antagonist to prevent the progression of tendinopathy in a
rat model.
AB - This study evaluated if inhibiting IL1-beta activity with an IL1-receptor
antagonist (IL1-RA) will prevent pathologic changes commonly seen in
tendinopathy. Thirty-six Sprague-Dawley retired-breeder rats were divided into
three groups having weekly bilateral patellar tendon injections: CON (0.1 ml
Saline), CAR (0.1 ml 2% carrageenan), IL1-RA (0.1 ml 2% CAR plus 0.94 mg of the
IL1-RA, 2.5 mg/kg). Carrageenan was used to establish tendinopathy in two groups
due to its ability to develop tendinopathy in prior studies. Animals were
euthanized 3 weeks after initial injection. The CAR group demonstrated
significantly (p < 0.05) shorter tendon lengths (8.61 +/- 0.38 mm) relative to
CON (8.94 +/- 0.38 mm) that was prevented in the IL1-RA (9.02 +/- 0.30 mm) as
well as significantly increased collagenase activity in the CAR (0.061 +/- 0.043)
compared to CON (0.027 +/- 0.015) (p< 0.05). By histological evaluation, the CAR
group demonstrated significantly greater inflammation than IL1-RA, and CON (p <
0.05). CAR showed a trend for increased cross-sectional area relative to CON that
was absent in the IL1-RA. IL1-RA can effectively inhibit the development of
mechanical, chemical, and histologic changes seen with carrageenan-induced
tendonitis.
PMID- 26418604
TI - Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD
foundation consensus recommendations based on state of the art review.
AB - Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, rare lung
disease resulting in chronic oto-sino-pulmonary disease in both children and
adults. Many physicians incorrectly diagnose PCD or eliminate PCD from their
differential diagnosis due to inexperience with diagnostic testing methods. Thus
far, all therapies used for PCD are unproven through large clinical trials. This
review article outlines consensus recommendations from PCD physicians in North
America who have been engaged in a PCD centered research consortium for the last
10 years. These recommendations have been adopted by the governing board of the
PCD Foundation to provide guidance for PCD clinical centers for diagnostic
testing, monitoring, and appropriate short and long-term therapeutics in PCD
patients.
PMID- 26418613
TI - Interplay of Substrate Conductivity, Cellular Microenvironment, and Pulsatile
Electrical Stimulation toward Osteogenesis of Human Mesenchymal Stem Cells in
Vitro.
AB - The influences of physical stimuli such as surface elasticity, topography, and
chemistry over mesenchymal stem cell proliferation and differentiation are well
investigated. In this context, a fundamentally different approach was adopted,
and we have demonstrated the interplay of inherent substrate conductivity,
defined chemical composition of cellular microenvironment, and intermittent
delivery of electric pulses to drive mesenchymal stem cell differentiation toward
osteogenesis. For this, conducting polyaniline (PANI) substrates were coated with
collagen type 1 (Coll) alone or in association with sulfated hyaluronan (sHya) to
form artificial extracellular matrix (aECM), which mimics the native
microenvironment of bone tissue. Further, bone marrow derived human mesenchymal
stem cells (hMSCs) were cultured on these moderately conductive (10(-4)-10(-3)
S/cm) aECM coated PANI substrates and exposed intermittently to pulsed electric
field (PEF) generated through transformer-like coupling (TLC) approach over 28
days. On the basis of critical analysis over an array of end points, it was
inferred that Coll/sHya coated PANI (PANI/Coll/sHya) substrates had enhanced
proliferative capacity of hMSCs up to 28 days in culture, even in the absence of
PEF stimulation. On the contrary, the adopted PEF stimulation protocol (7 ms
rectangular pulses, 3.6 mV/cm, 10 Hz) is shown to enhance osteogenic
differentiation potential of hMSCs. Additionally, PEF stimulated hMSCs had also
displayed different morphological characteristics as their nonstimulated
counterparts. Concomitantly, earlier onset of ALP activity was also observed on
PANI/Coll/sHya substrates and resulted in more calcium deposition. Moreover, real
time polymerase chain reaction results indicated higher mRNA levels of alkaline
phosphatase and osteocalcin, whereas the expression of other osteogenic markers
such as Runt-related transcription factor 2, Col1A, and osteopontin exhibited a
dynamic pattern similar to control cells that are cultured in osteogenic medium.
Taken together, our experimental results illustrate the interplay of multiple
parameters such as substrate conductivity, electric field stimulation, and aECM
coating on the modulation of hMSC proliferation and differentiation in vitro.
PMID- 26418614
TI - Contribution of Histopathologic Tissue Composition to Quantitative MR
Spectroscopy and Diffusion-weighted Imaging of the Prostate.
AB - PURPOSE: To determine associations of metabolite levels derived from magnetic
resonance (MR) spectroscopic imaging (ie, hydrogen 1 [(1)H] MR spectroscopic
imaging) and apparent diffusion coefficients (ADCs) from diffusion-weighted
imaging with prostate tissue composition assessed by digital image analysis of
histologic sections. MATERIALS AND METHODS: Institutional ethical review board
approved this retrospective study and waived informed consent. Fifty-seven
prostate cancer patients underwent an MR examination followed by prostatectomy.
One hematoxylin and eosin-stained section of the resected prostate per patient
was digitized and computationally segmented into nuclei, lumen, and combination
of epithelial cytoplasm and stroma. On each stained section, regions of interest
(ROIs) were chosen and matched to the corresponding ADC map and (1)H MR
spectroscopic imaging voxels. ADC and two metabolite ratios (citrate [Cit],
spermine [Spm], and creatine [Cr] to choline [Cho] and Cho to Cr plus Spm) were
correlated with percentage areas of nuclei, lumen, and cytoplasm and stroma for
peripheral zone (PZ), transition zone (TZ), and tumor tissue in both zones of the
prostate by using a linear mixed-effect model and Spearman correlation
coefficient (rho). RESULTS: ADC and (Cit + Spm + Cr)/Cho ratio showed positive
correlation with percentage area of lumen (rho = 0.43 and 0.50, respectively) and
negative correlation with percentage area of nuclei (rho = -0.29 and -0.26,
respectively). The Cho/(Cr + Spm) ratio showed negative association with
percentage area of lumen (rho = -0.40) and positive association with area of
nuclei (rho = 0.26). Percentage areas of lumen and nuclei, (Cit + Spm + Cr)/Cho
ratio, and ADC were significantly different (P < .001) between benign PZ (23.7
and 7.7, 8.83, and 1.58 * 10(-3) mm(2)/sec, respectively) and tumor PZ tissue
(11.4 and 12.5, 5.13, and 1.20 * 10(-3) mm(2)/sec, respectively). These
parameters were also significantly different between benign TZ (20.0 and 8.2,
6.50, and 1.26 * 10(-3) mm(2)/sec, respectively) and tumor TZ tissue (9.8 and
11.2, 4.36, and 1.03 * 10(-3) mm(2)/sec, respectively). CONCLUSION: The observed
correlation of (Cit + Spm + Cr)/Cho ratio and ADC of the prostate with its tissue
composition indicates that components of this composition, such as percentage
luminal area, contribute to the value of these MR parameters.
PMID- 26418616
TI - Tobacco industry interference with tobacco control policies in Poland: legal
aspects and industry practices.
AB - BACKGROUND: Since 2006, when Poland ratified the WHO Framework Convention on
Tobacco Control (FCTC), there have been efforts to improve tobacco control
regulation in the country. At the same time, at the European Union level, Poland
took part in discussions over revision of the Tobacco Tax Directive and the
Tobacco Products Directive. This study aims to explore the tobacco industry's
tactics to interfere with the creation of those policies. METHODS: Analysis of
257 documents obtained through freedom of information request. RESULTS: We
identified three means that the tobacco industry used to interfere with tobacco
control policies: creating a positive attitude, expressing a will to be a part of
the policymaking process, and exerting pressure. We found that those tactics have
often been used unethically, with the industry providing the government with
ready legislation proposals, overstating its contribution to the economy and the
government revenues, misrepresenting the illicit cigarette problem and misusing
scientific evidence. The industry also used legal threats, including use of
bilateral trade agreements, against implementation of tobacco control measures.
The companies lobbied together directly and through third parties, with the
cigarette excise tax structure being the only area of disagreement among the
companies. The industry also pushed the Polish government to challenge tobacco
control policies in countries with stronger public policy standards, including UK
display bans and the Australian plain-packaging law. CONCLUSIONS: From an object
of regulation, the tobacco industry in Poland became a partner with the
government in legislative work. Implementation of provisions of Article 5.3 of
the WHO FCTC could prevent further industry interference.
PMID- 26418615
TI - Hepatic Radiofrequency Ablation-induced Stimulation of Distant Tumor Growth Is
Suppressed by c-Met Inhibition.
AB - PURPOSE: To elucidate how hepatic radiofrequency (RF) ablation affects distant
extrahepatic tumor growth by means of two key molecular pathways. MATERIALS AND
METHODS: Rats were used in this institutional animal care and use committee
approved study. First, the effect of hepatic RF ablation on distant subcutaneous
in situ R3230 and MATBIII breast tumors was evaluated. Animals were randomly
assigned to standardized RF ablation, sham procedure, or no treatment. Tumor
growth rate was measured for 31/2 to 7 days. Then, tissue was harvested for Ki-67
proliferative indexes and CD34 microvascular density. Second, hepatic RF ablation
was performed for hepatocyte growth factor (HGF), vascular endothelial growth
factor (VEGF), and c-Met receptor expression measurement in periablational rim,
serum, and distant tumor 24 hours to 7 days after ablation. Third, hepatic RF
ablation was combined with either a c-Met inhibitor (PHA-665752) or VEGF receptor
inhibitor (semaxanib) and compared with sham or drug alone arms to assess distant
tumor growth and growth factor levels. Finally, hepatic RF ablation was performed
in rats with c-Met-negative R3230 tumors for comparison with the native c-Met
positive line. Tumor size and immunohistochemical quantification at day 0 and at
sacrifice were compared with analysis of variance and the two-tailed Student t
test. Tumor growth curves before and after treatment were analyzed with linear
regression analysis to determine mean slopes of pre- and posttreatment growth
curves on a per-tumor basis and were compared with analysis of variance and
paired two-tailed t tests. RESULTS: After RF ablation of normal liver, distant
R3230 tumors were substantially larger at 7 days compared with tumors treated
with the sham procedure and untreated tumors, with higher growth rates and tumor
cell proliferation. Similar findings were observed in MATBIII tumors. Hepatic RF
ablation predominantly increased periablational and serum HGF and downstream
distant tumor VEGF levels. Compared with RF ablation alone, RF ablation combined
with adjuvant PHA-665752 or semaxanib reduced distant tumor growth,
proliferation, and microvascular density. For c-Met-negative tumors, hepatic RF
ablation did not increase distant tumor growth, proliferation, or microvascular
density compared with sham treatment. CONCLUSION: RF ablation of normal liver can
stimulate distant subcutaneous tumor growth mediated by HGF/c-Met pathway and
VEGF activation. This effect was not observed in c-Met-negative tumors and can be
blocked with adjuvant c-Met and VEGF inhibitors.
PMID- 26418617
TI - A closer look at 'Cheap White' cigarettes.
AB - BACKGROUND: Given the prominence of Cheap Whites in illicit tobacco discussions,
we examined various definitions, market presence, brand proliferation,
manufacturers, production locations, trademark ownership, prices and compliance
with tax stamp and warning labels. METHODS: Data from peer-reviewed and grey
literature, newspapers, trademark registries, governments/international
organisation reports, and the tobacco industry were contrasted with two visual
legal requirements (tax stamps and warning labels) and prices from the Tobacco
Pack Surveillance System (TPackSS). RESULTS: Multiple sources identified 82 Cheap
White brands and 53 manufacturers operating at least 82 production facilities.
One-third of these manufacturers are in the free zones of Russia, Cyprus and the
UAE. Two-thirds of the 37 Cheap White brands in the TPackSS had neither the
correct health warning nor the required tax stamp in at least one country where
they were purchased. Cheap Whites are on average less expensive than all other
brands, but the price gap is often not as large as anecdotally reported. The
cheapest Cheap White cigarettes purchased in one of the TPackSS countries
irrespective of the presence of legal signs were still more expensive than the
least expensive other brands satisfying both legal requirements. CONCLUSIONS: We
confirmed that many Cheap White brands do not comply with the legal requirements
in countries where they are sold, but also found that some of these cigarettes
appear to be sold legally even outside their country of origin. The presence of
untaxed Cheap Whites undermines tobacco tax policies, while the availability of
legal cheap cigarettes is a public health concern.
PMID- 26418618
TI - In Vitro and In Vivo Evaluation of Cidofovir as a Topical Ophthalmic Antiviral
for Ocular Canine Herpesvirus-1 Infections in Dogs.
AB - PURPOSE: The effects of cidofovir were investigated against canine herpesvirus-1
(CHV-1) in vitro and in dogs with experimentally induced recurrent ocular CHV-1
infection, a host-adapted pathogen animal model of ocular herpes simplex virus-1
(HSV-1) infection. METHODS: The cidofovir EC50 was determined for CHV-1 and HSV
1. A randomized, masked vehicle-controlled trial was performed using beagles with
experimentally induced recurrent ocular CHV-1 infection. Dogs received 1 drop of
0.5% cidofovir solution or 0.9% sodium chloride solution (vehicle) in both eyes 2
times daily for 14 days. Dogs were monitored at intervals for 30 days by a
clinical ophthalmic examination, in vivo confocal microscopy of the cornea and
conjunctiva, ocular sample CHV-1 polymerase chain reaction assay, hemogram, and
serum biochemistry panel. Clinical ocular disease scores were calculated and
infiltrating leukocytes detected by in vivo confocal microscopy quantified.
RESULTS: Cidofovir displayed similar in vitro antiviral activity against CHV-1
and HSV-1. Clinical ocular disease scores were significantly higher in the
cidofovir group compared to the vehicle group. Marked conjunctival pigmentation
and blepharitis were also detected in the cidofovir group, but not the vehicle
group. Conjunctival and corneal leukocyte infiltration scores determined by in
vivo confocal microscopy were significantly higher in the cidofovir group. Dogs
administered cidofovir had significantly reduced durations of ocular viral
shedding compared to the vehicle group. Hemogram and serum biochemistry panel
values were unremarkable. CONCLUSIONS: Twice-daily application of topical 0.5%
cidofovir ophthalmic solution reduced the duration of ocular viral shedding in
dogs with experimentally induced recurrent ocular CHV-1 infection, but was
associated with local ocular toxicity.
PMID- 26418619
TI - Patterns of Feedback on the Bridge to Independence: A Qualitative Thematic
Analysis of NIH Mentored Career Development Award Application Critiques.
AB - BACKGROUND: NIH Mentored Career Development (K) Awards bridge investigators from
mentored to independent research. A smaller proportion of women than men succeed
in this transition. The aim of this qualitative study was to analyze reviewers'
narrative critiques of K award applications and explore thematic content of
feedback provided to male and female applicants. METHOD: We collected 88
critiques, 34 from 9 unfunded and 54 from 18 funded applications, from 70% (n =
26) of investigators at the University of Wisconsin-Madison with K awards funded
between 2005 and 2009 on the first submission or after revision. We qualitatively
analyzed text in the 5 critique sections: candidate, career development plan,
research plan, mentors, and environment and institutional commitment. We explored
thematic content within these sections for male and female applicants and for
applicants who had received a subsequent independent research award by 2014.
RESULTS: Themes revealed consistent areas of criticism for unfunded applications
and praise for funded applications. Subtle variations in thematic content
appeared for male and female applicants: For male applicants criticism was often
followed by advice but for female applicants it was followed by questions about
ability; praise recurrently characterized male but not female applicants'
research as highly significant with optimism for future independence. Female K
awardees that obtained subsequent independent awards stood out as having track
records described as "outstanding." CONCLUSION: This exploratory study suggests
that K award reviewer feedback, particularly for female applicants, should be
investigated as a potential contributor to research persistence and success in
crossing the bridge to independence.
PMID- 26418620
TI - Characteristics and role of dynamic membrane layer in anaerobic membrane
bioreactors.
AB - A submerged anaerobic dynamic membrane bioreactor (AnDMBR) was operated for
treatment of concentrated wastewater. The dynamic membrane (DM) or cake layer was
characterized on its physicochemical and biological composition and the role of
the DM layer in treatment and filtration performances was assessed. The results
showed that the DM layer had an important role in organic matter removal. Both
organic and inorganic materials, such as sludge particles, soluble microbial
products (SMP), extracellular polymeric substances (EPS), and Ca, N, P, Mg
precipitations contributed to the DM layer formation. Thus, effective retention
of very small particles by the DM layer was achieved. The DM layer had higher
microbial diversity and different microbial population composition in comparison
to the bulk sludge. Overall, this study provided a better understanding about the
DM layer structure in AnDMBRs, which might lead to increased applicability of
this promising technology for the treatment of concentrated wastewaters.
PMID- 26418622
TI - Speckle Tracking Echocardiography of the Right Atrium: The Neglected Chamber.
AB - The right atrium (RA) plays a pivotal role in electromechanical and endocrine
regulation of the heart. Its peculiar anatomical features and phasic mechanical
function make it distinct from ventricles. Various invasive and noninvasive
techniques have been used to elucidate RA structure and function. Of these
modalities, echocardiography has distinct advantages over others. Several
conventional measures of RA function through echocardiography have been described
in the literature, but they are load dependent. A relatively new technique is
speckle tracking-derived strain, which is relatively less dependent on loading
conditions. Speckle tracking echocardiography tracks acoustic scatters (speckles)
of myocardium frame-by-frame to calculate strain or deformation of the
myocardium. Speckle tracking echocardiography has been used extensively for
strain assessment of the right and left ventricle to detect subtle disease
pathology, to gain mechanistic insight, as a marker of ischemic metabolic memory,
as an endpoint in clinical trials, and as a functional assessment tool. The RA is
a relatively neglected chamber, as it is mostly studied for assessment of atrial
mass lesions, for electrophysiological studies, and in animal models for
physiological assessment. However, its role in the systolic and diastolic
function of the right heart, pulmonary vascular pathology, congenital heart
diseases, and combined electromechanical activation phenomena has been less
explored or unexplored. Speckle tracking echocardiography is an ideal tool for
the assessment of the RA because of its regional and global functional
characterization, angle independence, and high temporal resolution.
PMID- 26418621
TI - Toward Additive-Free Small-Molecule Organic Solar Cells: Roles of the Donor
Crystallization Pathway and Dynamics.
AB - The ease with which small-molecule donors crystallize during solution processing
is directly linked to the need for solvent additives. Donor molecules that get
trapped in disordered (H1) or liquid crystalline (T1) mesophases require additive
processing to promote crystallization, phase separation, and efficient light
harvesting. A donor material (X2) that crystallizes directly from solution yields
additive-free solar cells with an efficiency of 7.6%.
PMID- 26418623
TI - Fingerprint analysis and multi-component determination of Zibu Piyin recipe by
HPLC with DAD and Q-TOF/MS method.
AB - Zibu Piyin recipe (ZBPYR), a traditional Chinese medicine formula, is used for
curing dementia caused by diabetes. For quality control of ZBPYR, fingerprint
analysis and qualitative analysis using high-performance liquid chromatography
(HPLC) with a diode-array detector, and confirmation using HPLC coupled with
electrospray ionisation quadrupole time-of-flight tandem mass spectrometry (HPLC
Q-TOF-MS) were undertaken. HPLC fingerprint consisting of 34 common peaks was
developed among 10 batches of ZBPYR, in which 7 common peaks were identified in
comparison with the authentic standards and detected simultaneously. Furthermore,
these seven compounds were verified by HPLC-Q-TOF-MS methods. The method can be
applied to the quality control of ZBPYR.
PMID- 26418625
TI - DNA 5-hydroxymethylation in human adipose tissue differs between subcutaneous and
visceral adipose tissue depots.
AB - BACKGROUND: A stable intermediate during DNA demethylation, 5
hydroxymethylcytosine (5-hmC), raises questions about its function and
distribution. Therefore, we tested whether 5-hmC exists in human adipose tissue
depots and correlates with clinical variables. MATERIALS & METHODS: We measured
the % 5-hmC content in both subcutaneous adipose tissue and visceral adipose
tissue (VAT) from 81 individuals by using ELISA technology. To test for
associations with several clinical variables we used paired students t-tests and
linear regression analyses. RESULTS: We observed an average % 5-hmC content of
0.47% +/- 0.093 in subcutaneous adipose tissue, while VAT (0.51% +/- 0.122) is
higher hydroxymethylated (p = 0.005). In the total cohort we observed a positive
association of % 5-hmC in VAT with age (p = 0.034) and a negative relationship
with low density lipoprotein-cholesterol (p = 0.008). CONCLUSION: Our data
suggest adipose tissue depot specific 5-hmC levels with higher levels in VAT.
PMID- 26418627
TI - Granuloma Annulare Arising in Tumescent Anesthesia Injection Sites After
Endovenous Ablation.
PMID- 26418626
TI - Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis
in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria.
AB - To investigate the effects ofellagic acid (EA) on the cytotoxicity, B-lymphocytes
isolated from CLL patients and healthy individuals. Flow cytometric assay was
used to measure the percentage of apoptosis versus necrosis, intracellular active
oxygen radicals (ROS), mitochondrial membrane potential (MMP) and the caspase-3
activity and then mitochondria were isolated from both groups B-lymphocytes and
parameters of mitochondrial toxicity was investigated. Based on our results EA
decreased the percentage of viable cells and induced apoptosis. EA increased ROS
formation, mitochondria swelling, MMP decrease and cytochrome c release in
mitochondria isolated from CLL BUT NOT healthy B-lymphocytes while pre-treatment
with cyclosporine A and Butylated hydroxyl toluene (BHT) prevented these effects.
Our results suggest that EA can act as an anti cancer candidate by directly and
selectively targeting mitochondria could induce apoptosis through mitochondria
pathway with increasing ROS production which finally ends in cytochrome c
release, caspase 3 activation and apoptosis in cancerous B-lymphocytes isolated
from CLL patients.
PMID- 26418628
TI - Treatment of Actinic Cheilitis.
PMID- 26418629
TI - Results of a Multimodal Program During Hospitalization in Obese COPD Exacerbated
Patients.
AB - The objective of this study was to analyze the results of a multimodal
therapeutic program during hospitalization in obese AECOPD patients. This was a
randomized, single-blind clinical trial conducted at two university hospitals in
Granada, Spain. Forty-nine patients hospitalized due to AECOPD were randomly
allocated to a control group (CG), in which patients received standard care, or
to an intervention group (IG), in which patients were included in a multimodal
therapeutic program, added to the standard care. The main outcome measures were
pulmonary, physical (strength and exercise capacity) and perceived (dyspnea,
quality of life and psychological distress) variables. Within-group significant
improvements (p < 0.05) were found in physical and perceived variables in the IG
after the treatment. In the CG, a significant decrease was found in lower limb
strength and a significant improvement in dyspnea and in three subscales of the
EuroQol-5D questionnaire. The between-groups analysis showed significant
differences after the treatment on lower limb strength and exercise capacity
values (p < 0.05), in three of the EuroQol-5D subscales, and in the total score
and the depression subscale of the Hospital Anxiety and Depression Scale. A
multimodal therapeutic program has a beneficial effect on physical functioning
and perceived variables in hospitalized obese patients with AECOPD.
PMID- 26418630
TI - Electron-Proton Decoupling in Excited-State Hydrogen Atom Transfer in the Gas
Phase.
AB - Hydrogen-release by photoexcitation, excited-state-hydrogen-transfer (ESHT), is
one of the important photochemical processes that occur in aromatic acids and is
responsible for photoprotection of biomolecules. The mechanism is described by
conversion of the initial state to a charge-separated state along the O(N)-H bond
elongation, leading to dissociation. Thus ESHT is not a simple H-atom transfer in
which a proton and a 1s electron move together. Here we show that the electron
transfer and the proton-motion are decoupled in gas-phase ESHT. We monitor
electron and proton transfer independently by picosecond time-resolved near
infrared and infrared spectroscopy for isolated phenol-(ammonia)5 , a benchmark
molecular cluster. Electron transfer from phenol to ammonia occurred in less than
3 picoseconds, while the overall H-atom transfer took 15 picoseconds. The
observed electron-proton decoupling will allow for a deeper understanding and
control of of photochemistry in biomolecules.
PMID- 26418632
TI - Excavating abiotic stress-related gene resources of terrestrial macroscopic
cyanobacteria for crop genetic engineering: dawn and challenge.
AB - Genetically engineered (GE) crops with resistance to environmental stresses are
one of the most important solutions for future food security. Numerous genes
associated to plant stress resistance have been identified and characterized.
However, the current reality is that only a few transgenic crops expressing
prokaryotic genes are successfully applied in field conditions. These few
prokaryotic genes include Agrobacterium strain CP4 EPSPS gene, Bacillus
thuringiensis Cry1Ab gene and a bacterial chaperonin gene. Thus, the excavation
of potentially critical genes still remains an arduous task for crop engineering.
Terrestrial macroscopic cyanobacteria, Nostoc commune and Nostoc flagelliforme,
which exhibit extreme resistance to desiccation stress, may serve as new
prokaryotic bioresources for excavating critical genes. Recently, their marker
gene wspA was heterologously expressed in Arabidopsis plant and the transgenics
exhibited more flourishing root systems than wild-type plants under osmotic
stress condition. In addition, some new genes associated with drought response
and adaptation in N. flagelliforme are being uncovered by our ongoing RNA-seq
analysis. Although the relevant work about the terrestrial macroscopic
cyanobacteria is still underway, we believe that the prospect of excavating their
critical genes for application in GE crops is quite optimistic.
PMID- 26418631
TI - Heterogeneous composition of key metabolic gene clusters in a vent mussel
symbiont population.
AB - Chemosynthetic symbiosis is one of the successful systems for adapting to a wide
range of habitats including extreme environments, and the metabolic capabilities
of symbionts enable host organisms to expand their habitat ranges. However, our
understanding of the adaptive strategies that enable symbiotic organisms to
expand their habitats is still fragmentary. Here, we report that a single
ribotype endosymbiont population in an individual of the host vent mussel,
Bathymodiolus septemdierum has heterogeneous genomes with regard to the
composition of key metabolic gene clusters for hydrogen oxidation and nitrate
reduction. The host individual harbours heterogeneous symbiont subpopulations
that either possess or lack the gene clusters encoding hydrogenase or nitrate
reductase. The proportions of the different symbiont subpopulations in a host
appeared to vary with the environment or with the host's development.
Furthermore, the symbiont subpopulations were distributed in patches to form a
mosaic pattern in the gill. Genomic heterogeneity in an endosymbiont population
may enable differential utilization of diverse substrates and confer metabolic
flexibility. Our findings open a new chapter in our understanding of how
symbiotic organisms alter their metabolic capabilities and expand their range of
habitats.
PMID- 26418634
TI - Smooth Pursuit Eye Movement Deficits in Patients With Whiplash and Neck Pain are
Modulated by Target Predictability.
AB - STUDY DESIGN: This is a cross-sectional study. OBJECTIVE: The purpose of this
study is to support and extend previous observations on oculomotor disturbances
in patients with neck pain and whiplash-associated disorders (WADs) by
systematically investigating the effect of static neck torsion on smooth pursuit
in response to both predictably and unpredictably moving targets using video
oculography. SUMMARY OF BACKGROUND DATA: Previous studies showed that in patients
with neck complaints, for instance due to WAD, extreme static neck torsion
deteriorates smooth pursuit eye movements in response to predictably moving
targets compared with healthy controls. METHODS: Eye movements in response to a
smoothly moving target were recorded with video-oculography in a heterogeneous
group of 55 patients with neck pain (including 11 patients with WAD) and 20
healthy controls. Smooth pursuit performance was determined while the trunk was
fixed in 7 static rotations relative to the head (from 45 degrees to the left to
45 degrees to right), using both predictably and unpredictably moving stimuli.
RESULTS: Patients had reduced smooth pursuit gains and smooth pursuit gain
decreased due to neck torsion. Healthy controls showed higher gains for
predictably moving targets compared with unpredictably moving targets, whereas
patients with neck pain had similar gains in response to both types of target
movements. In 11 patients with WAD, increased neck torsion decreased smooth
pursuit performance, but only for predictably moving targets. CONCLUSION: Smooth
pursuit of patients with neck pain is affected. The previously reported WAD
specific decline in smooth pursuit due to increased neck torsion seems to be
modulated by the predictability of the movement of the target. The observed
oculomotor disturbances in patients with WAD are therefore unlikely to be induced
by impaired neck proprioception alone. LEVEL OF EVIDENCE: 3.
PMID- 26418633
TI - Association Between Preinfarction Angina and Angiographic Findings in Non-ST
Segment Elevation Myocardial Infarction.
AB - BACKGROUND: The association between preinfarction angina and angiographic
findings has not been elucidated in patients with non-ST-segment elevation
myocardial infarction (NSTEMI). HYPOTHESIS: Patients with preinfarction angina
have favorable angiographic findings. METHODS: This retrospective study analyzed
481 patients who underwent coronary angiography within 5 days of presenting
NSTEMI. Preinfarction angina was defined as experiencing >=1 chest-pain episode
within 7 days prior to admission. Infarct size was measured as the peak cardiac
troponin I (cTnI) level, and large myocardial infarction (MI) was defined as a
peak cTnI level >85th percentile value in the study population. Infarct-related
artery (IRA) patency was defined as Thrombolysis In Myocardial Infarction grade 2
or 3 flow. Clinical and angiographic characteristics and in-hospital mortality
were compared between patients with and without preinfarction angina. RESULTS:
Among 481 patients, 200 (42%) had preinfarction angina. Preinfarction angina was
associated with smaller infarct size, indicated by lower peak cTnI levels (P =
0.006) and lower incidence of large MI (P = 0.02), and IRA patency (P = 0.03).
There was no significant difference in in-hospital mortality. On multivariate
analysis, both preinfarction angina (odds ratio: 0.53, 95% confidence interval:
0.29-0.94, P = 0.03) and IRA patency (odds ratio: 0.30, 95% confidence interval:
0.17-0.52, P < 0.001) were independent negative predictors of large MI.
CONCLUSION: Our study demonstrates that preinfarction angina is a predictor of
smaller infarct size and infarct-related artery patency in NSTEMI patients,
suggesting that NSTEMI patients presenting without preinfarction angina are at
increased risk of developing a large MI.
PMID- 26418636
TI - [Insulin treatment of adults with type 1 diabetes].
AB - Whereas insulin treatment of type 1 diabetes formerly was limited by the
availability of one or a few types of insulin with suboptimal pharmacokinetic
properties, insulin analogues with more fitting physiological action profiles
have now been developed and ultimately near-physiological insulin treatment can
be delivered with insulin pumps. Adjustments of insulin dosing can be rationally
based on dosing algorithms. This requires frequent glucose measurements and
knowledge about dietary carbohydrate content. Today, the treatment and its
complexity are individualized according to needs and wishes of the patient.
PMID- 26418637
TI - [Diagnosing neck mass in adults].
AB - Doctors are frequently presented to patients with a neck mass, and the condition
might cause diagnostic challenges. In younger adults, a neck mass can typically
be explained by congenital, inflammatory or infectious causes. The highest
probability of neoplasms is found in patients above 40 years of age. When a
malignant neoplasm in the neck is suspected, patients should be referred to an
ear, nose and throat specialist. In cases of suspect signs of malignancy as
defined by the Danish Health and Medicines Authority, patients should be referred
to the integrated national cancer pathways.
PMID- 26418635
TI - Altered miRNA expression in the cervix during pregnancy associated with lead and
mercury exposure.
AB - AIM: Toxic metals including lead and mercury are associated with adverse
pregnancy outcomes. This study aimed to assess the association between miRNA
expression in the cervix during pregnancy with lead and mercury levels. MATERIALS
& METHODS: We obtained cervical swabs from pregnant women (n = 60) and quantified
cervical miRNA expression. Women's blood lead, bone lead and toenail mercury
levels were analyzed. We performed linear regression to examine the association
between metal levels and expression of 74 miRNAs adjusting for covariates.
RESULTS: Seventeen miRNAs were negatively associated with toenail mercury levels,
and tibial bone lead levels were associated with decreased expression of miR-575
and miR-4286. CONCLUSION: The findings highlight miRNAs in the human cervix as
novel responders to maternal chemical exposure during pregnancy.
PMID- 26418638
TI - [Synchronous sigmoideum- and caecum volvulus].
AB - This case presents a synchronous sigmoid- and caecum volvulus in a 69-year old
man with Parkinson's disease, hypertension and previous history of colonic
volvulus. On admission the patient had abdominal pain, nausea, vomiting and
constipation. The CT scan showed a sigmoid volvulus with a dilated caecum. The
synchronous sigmoideum- and caecum volvulus was diagnosed intraoperatively. Total
colectomy and ileostomy was performed.
PMID- 26418639
TI - [Myoclonus as a side effect to citalopram treatment in a patient with liver
cirrhosis].
AB - Side effects such as myoclonus and tremor are rare when treating with selective
serotonin reuptake inhibitors (SSRIs). We present a case where a patient with
known liver cirrho-sis and in treatment with citalopram developed myoclonus,
tremor and gait difficulties. The symptoms were reduced when the SSRI dose was
decreased. In patients with unexplained movement disorders the usage of SSRIs
should be considered as a cause. Furthermore, treatment with SSRIs should be
carefully assessed in patients with reduced liver function.
PMID- 26418640
TI - [Median arcuate ligament syndrome].
AB - The median arcuate ligament syndrome is a rare entity and poorly described in
Danish literature. The syndrome is a diagnosis of exclusion and is characterized
by chronic abdominal pain, postprandial pain and weight loss. It is believed that
the median arcuate ligament, being a fibrous structure of diaphragm, compresses
the coeliac trunk thus causing stenosis and malperfusion of the gastrointestinal
organs. Until recently, there has been some reluctance to consider intervention
with revascularization or ligament release. Within the latest decade minimally
invasive techniques, including laparoscopic release of the median arcuate
ligament, have shown promising results.
PMID- 26418642
TI - Surgery is not an innate talent: the dark side of duty-hour restrictions for
residents.
PMID- 26418641
TI - [Anorexia nervosa is frequently associated with psychiatric co-morbidity].
AB - Recent literature is explored focusing on the relationship between symptoms of
anorexia nervosa (AN) and other psychiatric disorders and lines of treatment. In
AN, restrictive subtype, anxiety and obsessive-compulsive disorders are the most
frequent co-morbidities. In AN, bulimic subtype, depression, emotional
instability/borderline and dependency disorders are most frequent.
Psychopharmacological treatment could be tried in cases with AN and co-morbid
depression, but otherwise the evidence base is lacking and pharmacological
treatment relies on case stories and experience.
PMID- 26418644
TI - Comparison of parental socio-demographic factors in children and adolescents
presenting with internalizing and externalizing disorders.
AB - OBJECTIVE: This study aimed to: (a) examine parental socio-demographic factors in
children and adolescents referred to an outpatient service for internalizing and
externalizing disorders, and (b) compare the demographic variables and diagnoses
for the two diagnostic groups. METHODS: Parents of all children who were referred
to the child and adolescent outpatient service were asked to participate.
Following their informed consent, they completed a socio-demographic
questionnaire for themselves and a Child Behaviour Checklist (CBCL) for their
child. The CBCL scores and the diagnoses assigned by the psychiatrists were then
recorded for each child. Diagnoses were classified as internalizing or
externalizing based on the primary DSM-IV diagnosis assigned by the
psychiatrists. Data for the two groups were compared for study variables using
Pearson correlation, t-tests, one-way ANOVA and logistic regression. RESULTS:
Children who had externalizing disorders tended to live with unemployed single
parents who had lower education levels and lived in rented or assisted housing.
Children with internalizing problems tended to live in owned homes with employed
parents. There was no significant association between age or gender for either
group. CONCLUSION: Previous literature has reported an association between low
SES and more mental health problems; however, the relationship between different
indicators of SES and diagnosis is not clear. Despite small numbers, our study
revealed significant differences between the parental socio-demographic factors
for externalizing compared with internalizing disorders.
PMID- 26418645
TI - Role of iso-receptors in receptor-receptor interactions with a focus on dopamine
iso-receptor complexes.
AB - Intercellular and intracellular communication processes consist of signals and
recognition/decoding apparatuses of these signals. In humans, the G protein
coupled receptor (GPCR) family represents the largest family of cell surface
receptors. More than 30 years ago, it has been proposed that GPCR could form
dimers or higher-order oligomers (receptor mosaics [RMs] at the plasma membrane
level and receptor-receptor interactions [RRIs] have been proposed as a new
integrative mechanism for chemical signals impinging on cell plasma membranes).
The basic phenomena involved in RRIs are allostery and cooperativity of membrane
receptors, and the present paper provides basic information concerning their
relevance for the integrative functions of RMs. In this context, the possible
role of iso-receptor RM is discussed (with a special focus on dopamine receptor
subtypes and on some of the RMs they form with other dopamine iso-receptors), and
it is proposed that two types of cooperativity, namely, homotropic and
heterotropic cooperativity, could allow distinguishing two types of functionally
different RMs. From a general point of view, the presence of iso-receptors and
their topological organization within RMs allow the use of a reduced number of
signals for the intercellular communication processes, since the target cells can
recognize and decode the same signal in different ways. This theoretical aspect
is further analyzed here by means of an analogy with artificial information
systems. Thus, it is suggested that the 'multiplexer' and 'demultiplexer'
concepts could, at least in part, model the role of RMs formed by iso-receptors
in the information handling by the cell.
PMID- 26418646
TI - Adaptive regulation of glucose transport, glycolysis and respiration for cell
proliferation.
AB - The cell must utilise nutrients to generate energy as a means of sustaining its
life. As the environment is not necessarily abundant in nutrients and oxygen, the
cell must be able to regulate energy metabolism to adapt to changes in
extracellular and intracellular conditions. Recently, several key regulators of
energy metabolism have been reported. This review describes the recent advances
in molecular regulation of energy metabolism, focusing mainly on glycolysis and
its shunt pathways. Human diseases, such as cancer and neurodegenerative
disorders, are also discussed in relation to failure of energy metabolism
regulation.
PMID- 26418647
TI - Vector competence of two Indian populations of Culex quinquefasciatus (Diptera:
Culicidae) mosquitoes to three West Nile virus strains.
AB - BACKGROUND & OBJECTIVES: Culex quinquefasciatus is one of the principal vectors
of West Nile virus (WNV). The mosquito also acts as a bridge vector as it feeds
on both birds and humans. In the background of the recent reports of WNV activity
in Kerala and Assam with fatalities, a study was initiated to determine the
growth kinetics and transmission mechanisms of three strains of WNV in two
populations of Cx. quinquefasciatus. METHODS: Mosquitoes were infected by oral
feeding and growth on different post-infection days was determined with the three
strains. Horizontal transmission was determined by confirming sickness and
mortality in infant mice after infected mosquito bite. F1 generation eggs,
larvae, pupae and adults of experimentally infected mosquitoes were screened for
WNV to determine vertical (transovarial) transmission. Trans-stadial transmission
was determined by detecting WNV in adult mosquitoes emerged from infected larvae.
RESULTS: Both the mosquito populations replicated and maintained WNV for a
prolonged period with high titers (>= 5log10 PFU/ml). WNV could be detected in
saliva from Days 2 to 32 post-infection. Horizontal transmission by both the
populations could be established but no vertical transmission was observed.
However, parenterally infected larvae transmitted WNV to adults. INTERPRETATION &
CONCLUSION: WNV has been isolated from >10 mosquito species from India, however,
vector competence of none of the species has been studied. The present study
demonstrates efficient transmission of WNV by Cx. quinquefasciatus mosquitoes.
With its country wide prevalence and high vector competence, the mosquitoes could
create grave consequences especially when virulent strains with potential to
cause acute flaccid paralysis and death are circulating.
PMID- 26418648
TI - Fly ash based Bacillus thuringiensis var. israelensis formulation for use against
Culex quinquefasciatus, the vector of filariasis in natural ecosystems.
AB - BACKGROUND & OBJECTIVES: Fly ash is produced in huge quantities by the various
thermal power stations in India. This thermal waste has been employed as a
carrier material in the preparation of a biopesticidal water dispersible powder
(WDP) formulation for use against mosquitoes. In the present investigation, this
newly developed fly ash based WDP formulation was evaluated in natural breeding
habitats of mosquito. METHODS: Fly ash based WDP formulation of Bacillus
thuringiensis var. israelensis (VCRC B17) was evaluated for its efficacy and
residual activity in aquatic habitats supporting breeding of Culex
quinquefasciatus, the vector of lymphatic filariasis in Neyveli Township, Neyveli
Lignite Corporation, India for a period of one month. RESULTS: At an application
rate of 10 kg/ha, the WDP was effective for five days regardless of the habitat,
and provided 80-100% reduction in larval abundance of Cx. quinquefasciatus.
INTERPRETATION & CONCLUSION: The study indicates that for continued control of
immature density and prevention of adult emergence, a weekly application of this
formulation is necessary. This study also showed that fly ash based formulations
can be used for immediate control of mosquitoes in different types of habitats
and has also brought out a new avenue for the utilization of coal ash.
PMID- 26418649
TI - Vector ecology of human schistosomiasis in south India and description of a new
species of the genus Ferrissia (Mollusca: Gastropoda: Planorbidae).
AB - BACKGROUND & OBJECTIVES: Vector ecology and taxonomy of snails is a prerequisite
for controlling schistosomiasis in the tropics. The ecology of the freshwater
limpet genus Ferrissia was investigated for detection of cercariae larvae in
them, and taxonomic description of a new species of the genus Ferrissia. METHODS:
This study was conducted in 15 perennial streams from five different hills of
south India. To study the seasonal patterns, a stream from each hill was selected
and sampled in three seasons. In each study site, triplicate sampling was done
and specimens were collected from stream substrates as well as waste material
submerged in stream. Microscopic examination was carried out for detecting
cercariae larvae in limpets. RESULTS: Three freshwater limpets (F. tenuis, F.
verruca and F. fivefallsiensis) were observed. Seasonality influenced the
abundance of limpets. The highest abundance was observed during post-monsoon
(December and January). The distribution of Ferrissia was observed at riffle in
pebbles, leaf litter and wastes (polyethylene bags and snacks cover) submerged in
water. No cercariae larvae were found from the body of limpets. In this study, we
described a new species of Ferrissia fivefallsiensis. INTERPRETATION &
CONCLUSION: Our results showed the distribution, habitat preference and
seasonality of limpets, and recommend the detection of Schistosoma from limpets
as well as human samples by use of molecular tools.
PMID- 26418650
TI - Microfilarial periodicity of Wuchereria bancrofti in Assam, Northeast India.
AB - BACKGROUND & OBJECTIVES: Wuchereria bancrofti has shown nocturnal periodicity in
India and other endemic countries of the world except pacific regions where non
periodic or diurnal sub-periodic forms have been reported. Presence of sub
periodic form of W. bancrofti in Andaman and Nicobar Islands, India and a case
report of sub- periodic form of W. bancrofti from Mysore, India provide basis for
exploring the periodicity pattern of microfilaria of W. bancrofti prevalent in
Assam, Northeastern region of India. State of Assam has unique geographical
location as its Northeastern region shares international boundaries with Nepal,
China, Bhutan, Myanmar and Bangladesh. Evolutionary association of W. bancrofti
found in Assam is not known and possibility of its link with W. bancrofti form,
prevalent in neighbouring countries may not be ruled out. Hence, this study was
undertaken to know the microfilarial periodicity of W. bancrofti in Assam.
METHODS: Ten microfilaria positive adult male individuals having moderate to high
microfilaraemia were selected. Informed written consent from each participant was
obtained. The presence of microfilaria was observed at two hourly intervals over
a period of 24 h using 50 MUl of finger prick peripheral blood samples.
Peripheral blood smears were processed, stained and examined under microscope and
microfilaria counts were recorded. RESULTS: Data collected were calculated and
analyzed using modified statistical method, and the periodicity curve was
prepared. Typical nocturnal periodicity was observed at a peak time of 0003 hrs
with a periodicity index of 136.2. INTERPRETATION & CONCLUSION: Analysis of the
data revealed nocturnal periodicity of the W. bancrofti prevalent in the Assam
with peak periodicity about one hour ahead of the other states in India. Findings
will be helpful in evaluation and monitoring of ongoing MDA programme for
elimination of LF in Assam.
PMID- 26418651
TI - Potential urban distribution of Phlebotomus mascittii Grassi and Phlebotomus
neglectus Tonn. (Diptera: Psychodidae) in 2021-50 in Budapest, Hungary.
AB - BACKGROUND & OBJECTIVES: In the Carpathian Basin, the most northern populations
of Phlebotomus (sandfly) species, including the two studied species (Phlebotomus
mascittii and Phlebotomus neglectus), are reported from central Hungary. The most
important limiting factor of the distribution of Phlebotomus species in the
region is the annual minimum temperature which may be positively affected by the
urban heat island and the climate change in the future. The main objective of the
study is to prove and predict the overwintering possibility of Phlebotomus
species in urban environment. METHODS: Based on the latest reports of occurrence
of sandfly species, climate envelope model was built for the period 1961-90 and
2025-50 to project the potential urban distribution of the species. The climatic
data were obtained from RegCM regional climate model and MODIS satellite images.
RESULTS: The recent occurrence of the species in central Hungary indicates that
Phlebotomus species can overwinter in non-heated shelters in built environment.
INTERPRETATION & CONCLUSION: Jointly heat island and the increase of minimum
temperature in winter due to climate change seem to be able to provide suitable
environment for the studied species in urban areas to a great extent.
PMID- 26418652
TI - Confirmation of Culex (Culex) tritaeniorhynchus summorosus (Diptera: Culicidae)
as a separate species.
AB - BACKGROUND & OBJECTIVES: Culex tritaeniorhynchus, a member of Cx. vishnui
subgroup, is an important vector of Japanese encephalitis (JE) virus. Cx.
tritaeniorhynchus summorosus considered as a variety or subspecies of Cx.
tritaeniorhynchus, has been studied in detail to settle its taxonomic status.
Surveys for the collection of Cx. tritaeniorhynchus from Chandigarh and adjoining
areas have established the availability of Cx. summorosus from this area.
METHODS: For the present investigation, collections have been made from
Chandigarh and its adjoining areas (up to 60 km) for procuring the material. The
detailed morphology including scanning electron microscopy of immatures (eggs and
larvae) and adults of Cx. tritaeniorhynchus and Cx. summorosus has been studied
and compared. Further, the interbreeding experiments of the two species were also
conducted and efforts had been made to allow cross- breeding among the members of
these two species. RESULTS: Comparison of egg, larval and adult morphology of Cx.
summorosus with the parental species Cx. tritaeniorhynchus under the light and
electron microscope, revealed significant differences. Moreover, these two
species have also been found to be reproductively isolated as indicated by
laboratory experiments. This settles the controversy on the status of Cx.
summorosus and confirms its status as a distinct species. INTERPRETATION &
CONCLUSION: The study establishes that the two species show considerable number
of differences which are sufficient to consider them as separate species rather
than subspecies or variant of Cx. tritaeniorhynchus. Furthermore, the absence of
interbreeding between these two again confirms their separate specific status
according to biological species concept. But, it is yet to ascertain whether Cx.
summorosus is a vector of Japanese encephalitis like Cx. tritaeniorhynchus or
not.
PMID- 26418654
TI - Anopheline mosquitoes in District Ramgarh (Jharkhand), India.
AB - BACKGROUND & OBJECTIVES: Jharkhand is one of the highly malaria endemic states in
India and experiencing vast ecological and human-induced changes over the years.
These changes have provided more favourable conditions for malaria transmission
in the region. The present study was carried out to find out the distribution and
prevalence of anopheline vector and non-vector species in District Ramgarh of
Jharkhand state. METHODS: Daytime indoor resting adult female anopheline
mosquitoes were collected from four subcentres comprising of eight study villages
in District Ramgarh. The collections were made from fixed as well as random human
dwellings and cattlesheds on fortnightly basis using manual aspiration method
from January to December 2012. Mosquito identification was done by using standard
identification keys. RESULTS: A total of 18,875 anophelines belonging to 19
species were collected. Of these, 61.87% were vector species (An. culicifacies,
An. fluviatilis and An. annularis). Of total vector collection, 57.44% was
observed in Gola block and 42.55% in Ramgarh. An. culicifacies was predominant
species followed by An. fluviatilis and An. annularis in the study area. Out of
19, eight anopheline species exhibited successional changes in their composition
over the period of years. Statistical analysis revealed positive correlation
between meteorological variables and man hour density in case of An.
culicifacies, whereas these were negatively correlated in case of An. fluviatilis
and An. annularis. INTERPRETATION & CONCLUSION: The study revealed the prevalence
of three recognised malaria vector species (An. culicifacies, An. fluviatilis and
An. annularis) in high density throughout the year in this area, which indicates
possibility of widening of malaria transmission window in the presence of malaria
parasites. The shifting of anopheline species in Ramgarh also indicate alteration
in ecological, environmental and sociological conditions, which necessitate
routine monitoring on ecology and successional changes of vector species as well
as malariological survey for management and adoption of appropriate vector
control strategies in this area.
PMID- 26418653
TI - Control of Aedes aegypti and Ae. albopictus, the vectors of dengue and
chikungunya, by using pheromone C21 with an insect growth regulator: Results of
multicentric trials from 2007-12 in India.
AB - BACKGROUND & OBJECTIVES: Aedes mosquito control has gained much importance
nowadays in view of rise in number of reported cases of dengue and chikungunya in
India and other countries. In the present study, C21 attracticide (containing a
pheromone and an insect growth regulator-IGR, developed by Defence Research and
Development Establishment (DRDE), Gwalior, India was tested for its feasibility
for surveillance and control of Aedes mosquito in a multicentric mode from
October 2007 to June 2012 in urban (Delhi, and Bengaluru district, Karnataka) and
suburban (Alappuzha district, Kerala) settings of the country in three phases.
METHODS: Across the randomly selected households in each study area, two to four
containers treated with attracticide (experimental) and untreated (control) were
placed and monitored by trained surveillance workers on weekly/ fortnightly basis
for determining the presence of eggs, larvae and pupae. Container positivity,
percent larvae, egg and pupae collected were determined during different phases
and analyzed statistically using SPSS 18.0. RESULTS: Container positivity was
found statistically significant at Bengaluru and Alappuzha, Kerala while in
Delhi, it was found non-significant. Eggs collected from experimental containers
were significantly higher in comparison to control at all the locations except
Delhi. Also larvae collected from control containers were significantly higher at
all the locations except Bengaluru. Pupae collected from control containers
remained significantly higher at all the locations as no pupal formation was
recorded from experimental containers. INTERPRETATION & CONCLUSION: The use of
C21 attracticide hampered pupal formation, thus inhibiting adult population in
the study areas. The study established that C21 attracticide was efficacious in
the field conditions and has potential for use in surveillance and management of
dengue and chikungunya mosquitoes.
PMID- 26418655
TI - Pattern and predictors of neurological morbidities among childhood cerebral
malaria survivors in central Sudan.
AB - BACKGROUND & OBJECTIVES: Cerebral malaria is considered a leading cause of neuro
disability in sub-Saharan Africa among children and about 25% of survivors have
long-term neurological and cognitive deficits or epilepsy. Their development was
reported to be associated with protracted seizures, deep and prolonged coma. The
study was aimed to determine the discharge pattern and to identify potential and
informative predictors of neurological sequelae at discharge, complicating
childhood cerebral malaria in central Sudan. METHODS: A cross-sectional
prospective study was carried out during malaria transmission seasons from 2000
to 2004 in Wad Medani, Sinnar and Singa hospitals, central Sudan. Children
suspected of having cerebral malaria were examined and diagnosed by a
Pediatrician for clinical, laboratory findings and any neurological
complications. Univariate and multiple regression model analysis were performed
to evaluate the association of clinical and laboratory findings with occurrence
of neurological complications using the SPSS. RESULTS: Out of 940 examined
children, only 409 were diagnosed with cerebral malaria with a mean age of 6.1 +/
3.3 yr. The mortality rate associated with the study was 14.2% (58) and 18.2%
(64) of survivors (351) had neurological sequelae. Abnormal posture, either
decerebration or decortication, focal convulsion and coma duration of >48 h were
significant predictors for surviving from cerebral malaria with a neurological
sequelae in children from central Sudan by Univariate analysis. Multiple logistic
regression model fitting these variables, revealed 39.6% sensitivity for
prediction of childhood cerebral malaria survivors with neurological sequelae (R2
= 0.396; p=0.001). INTERPRETATION & CONCLUSION: Neurological sequelae are common
due to childhood cerebral malaria in central Sudan. Their prediction at
admission, clinical presentation and laboratory findings may guide clinical
intervention and proper management that may decrease morbidity and improve CM
consequences.
PMID- 26418656
TI - Oviposition and vertical dispersal of Aedes mosquitoes in multiple storey
buildings in Colombo district, Sri Lanka.
AB - BACKGROUND & OBJECTIVES: The Colombo City in Sri Lanka is experiencing tremendous
development and construction of multiple storey buildings and high rise
apartments. The change in housing types and microhabitats might have altered the
flight and breeding behaviour of Aedes mosquito population. This study was
carried out to determine the vertical dispersal and abundance of Aedes mosquitoes
in multiple storey buildings in the Colombo district, with respect to abiotic
factors such as rainfall, humidity and wind speed. Hence, this study is of
paramount importance, particularly for planning and implementation of control
measures against Aedes mosquitoes. METHODS: An ovitrap based study was carried
out at four selected multiple storey buildings in four residential areas located
in Colombo, Sri Lanka, from August to December 2013. Results were analyzed using
four indices; ovitrap index, mean number of larvae, mean number of eggs and mean
number of larvae per ovipaddle. RESULTS: The results implied that Aedes
mosquitoes could be found in different elevations from ground floor to the
highest floor (130 ft). There was a significant difference between height and
ovitrap index (p<0.05), and height and mean number of larvae per recovered
ovipaddle (p<0.05). The highest index value for mean number of eggs was observed
as 3.492 +/- 0.655 at the 6th floor (60 ft high from ground level). At the same
height (60 ft height) other indices (ovitrap index, mean number of larvae and
mean number of larvae per ovipaddle) also displayed higher values, i.e. 13.19 +/-
2.98%, 1.366 +/- 0.527, and 2.070 +/- 0.421%, respectively. Abiotic factors such
as wind speed, coastal nature, etc. displayed a significant effect to the
vertical dispersal of Aedes mosquitoes (p<0.05). INTERPRETATION & CONCLUSION: The
study suggested that Aedes mosquitoes are able to breed at any level of the
buildings and not restricted by their height. The indices (mean number of larvae,
mean number of eggs) representing the vertical dispersal with respect to
abundance seemed to be statistically non-significant (p>0.05) with height which
indicates high abundance of Aedes mosquitoes at higher floors. Abiotic factors
also seemed to cause significant effect to the vertical dispersal of Aedes
mosquitoes in high rise buildings.
PMID- 26418657
TI - Seasonal prevalence and blood meal analysis of filarial vector Culex
quinquefasciatus in coastal areas of Digha, West Bengal, India.
AB - BACKGROUND & OBJECTIVES: Filariasis is one of the major vector-borne diseases
causing serious health problem in the tropics and subtropics. The coastal areas
of Digha are known to be a filariasis prone region of West Bengal, India. The
filarial parasite Wuchereria bancrofti is transmitted by Culex quinquefasciatus,
the established filarial vector in West Bengal, India. The present work was aimed
to determine the abundance of different mosquito species; and the frequency,
distribution and blood meal analysis of Cx. quinquefasciatus in coastal areas of
Digha. METHODS: During the present study, a total of 11,537 mosquitoes [Cx.
quinquefasciatus, Armigeres subalbatus, Anopheles barbirostris, An. annularis,
An. subpictus, An. sundaicus, Aedes albopictus, and Cx. vishnui (group)] were
collected by hand collection method from human habitations and cattlesheds of 10
villages of Digha, West Bengal, India. The seasonal prevalence of Cx.
quinquefasciatus was studied. In each season, blood meals of 300 Cx.
quinquefasciatus collected from human habitations were analysed during the study
period. RESULTS: Cx. quinquefasciatus was found to be the dominant species
(88.44% of the total collection) in the study area. It was most frequently found
in and around human habitations than cattlesheds. Total man hour density
calculation revealed that this species was most prevalent during the rainy
season. Two-way ANOVA revealed that the abundance of Cx. quinquefasciatus varied
with different seasons. Blood meal analysis showed that the filarial vector
preferred human blood than that of other animals. INTERPRETATION & CONCLUSION:
This study suggested Cx. quinquefasciatus as the dominant mosquito species in the
study area; and the anthropophilic nature of Cx. quinquefasciatus might be the
reason of increase in the intensity of filarial transmission in coastal areas of
Digha.
PMID- 26418658
TI - Molecular phylogenetic affiliation of Wolbachia and phage WO among Mansonia
mosquitoes from Kerala, India.
PMID- 26418659
TI - Deltamethrin induced functional mortality of Anopheles stephensi, the urban
malaria vector, in relation to resistance development.
PMID- 26418660
TI - Hepatitis A and dengue coinfection.
PMID- 26418661
TI - Atypical eschar: An unusual cutaneous manifestation of scrub typhus.
PMID- 26418662
TI - Cheek swelling: An unusual presentation of filariasis.
PMID- 26418663
TI - Corrigendum.
PMID- 26418664
TI - Prevalence of Restless Legs Syndrome in Adult ADHD and Its Subtypes.
AB - In this observational cross-sectional study, 49 subjects were assessed for sleep
disorders and for ADHD symptoms. Thirty-six received an ADHD diagnosis (29:
combined type (ADHD-C); 7: inattentive type). An RLS and RLS symptoms prevalence
of 34.5% was found, with a higher prevalence rate in the ADHD-C subgroup,
although not significantly (p = 0.066). RLS symptoms were correlated with
particularly hyperactivity-impulsivity (rho = 0.742; p: 0.000). ADHD patients
with positive RLS scores reported higher scores on the ADHD-Rating scale compared
with patients with negative RLS scores (Z: -2.968, p = 0.003), mainly due to
higher hyperactivity-impulsivity scores (Z: -3.145; p = 0.002). Our findings show
that clinicians need to be aware of RLS among adult ADHD patients, particularly
those with severe hyperactivity-impulsivity symptoms.
PMID- 26418665
TI - Rare-earth metal methylidene complexes with Ln3(MU3-CH2)(MU3-Me)(MU2-Me)3 core
structure.
AB - Trinuclear rare-earth metal methylidene complexes with a Ln3(MU3-CH2)(MU3-Me)(MU2
Me)3 structural motif were synthesized by applying three protocols. Polymeric
[LuMe3]n (1-Lu) reacts with the sterically demanding amine H[NSiMe3(Ar)] (Ar =
C6H3iPr2-2,6) in tetrahydrofuran via methane elimination to afford isolable
monomeric [NSiMe3(Ar)]LuMe2(thf)2 (4-Lu). The formation of trinuclear rare-earth
metal tetramethyl methylidene complexes [NSiMe3(Ar)]3Ln3(MU3-CH2)(MU3-Me)(MU2
Me)3(thf)3 (7-Ln; Ln = Y, Ho, Lu) via reaction of [LnMe3]n (1-Ln; Ln = Y, Ho, Lu)
with H[NSiMe3(Ar)] is proposed to occur via an "intermediate" species of the type
[NSiMe3(Ar)]LnMe2(thf)x and subsequent C-H bond activation. Applying Lappert's
concept of Lewis base-induced methylaluminate cleavage, compounds
[NSiMe3(Ar)]Ln(AlMe4)2 (5-Ln; Ln = Y, La, Nd, Ho) were converted into methylidene
complexes 7-Ln (Ln = Y, Nd, Ho) in the presence of tetrahydrofuran. Similarly,
tetramethylgallate complex [NSiMe3(Ar)]Y(GaMe4)2 (6-Y) could be employed as a
synthesis precursor for 7-Y. The molecular composition of complexes 4-Ln, 5-Ln, 6
Y and 7-Ln was confirmed by elemental analyses, FTIR spectroscopy, (1)H and (13)C
NMR spectroscopy (except for holmium derivatives) and single-crystal X-ray
diffraction. The Tebbe-like reactivity of methylidene complex 7-Nd with 9
fluorenone was assessed affording oxo complex [NSiMe3(Ar)]3Nd3(MU3-O)(MU2
Me)4(thf)3 (8-Nd). The synthesis of 5-Ln yielded [NSiMe3(Ar)]2Ln(AlMe4) (9-Ln; Ln
= La, Nd) as minor side-products, which could be obtained in moderate yields when
homoleptic Ln(AlMe4)3 were treated with two equivalents of K[NSiMe3(Ar)].
PMID- 26418666
TI - Adjunctive Non-Surgical Therapy of Inflamed Periodontal Pockets During
Maintenance Therapy Using Diode Laser: A Randomized Clinical Trial.
AB - BACKGROUND: Numerous studies have documented the clinical outcomes of laser
therapy for untreated periodontitis, but very few have reported on lasers
treating inflamed pockets during maintenance therapy. The aim of this study is to
compare the effectiveness of scaling and root planing (SRP) plus the adjunctive
use of diode laser therapy to SRP alone on changes in the clinical parameters of
disease and on the gingival crevicular fluid (GCF) inflammatory mediator
interleukin-1beta (IL-1beta) in patients receiving regular periodontal
maintenance therapy. METHODS: This single-masked and randomized, controlled,
prospective study includes 22 patients receiving regular periodontal maintenance
therapy who had one or more periodontal sites with a probing depth (PD) >= 5 mm
with bleeding on probing (BOP). Fifty-six sites were treated with SRP and
adjunctive laser therapy (SRP + L). Fifty-eight sites were treated with SRP
alone. Clinical parameters, including PD, clinical attachment level (CAL), and
BOP, and GCF IL-1beta levels were measured immediately before treatment
(baseline) and 3 months after treatment. RESULTS: Sites treated with SRP + L and
SRP alone resulted in statistically significant reductions in PD and BOP and
gains in CAL. These changes were not significantly different between the two
therapies. Similarly, differences in GCF IL-1beta levels between SRP + L and SRP
alone were not statistically significant. CONCLUSION: In periodontal maintenance
patients, SRP + L did not enhance clinical outcomes compared to SRP alone in the
treatment of inflamed sites with >= 5 mm PD.
PMID- 26418667
TI - Comparative modeling of exposure to airborne nanoparticles released by consumer
spray products.
AB - Consumer exposure to sprays containing nano-objects is a continuing concern as a
potential health hazard. One potential hazard has been formulated in the overload
hypothesis. It describes a volume fraction of the macrophages that is occupied by
deposited nanoparticles that leads to reduced macrophage mobility. Subsequent
chronic inflammation may then lead to severe health consequences including
cancer. To calculate lung deposition of spherical particles, the Multiple-Path
Particle Dosimetry (MPPD) model (ARA, Albuquerque, NM) provides different kinds
of lung models and age settings. Using the MPPD v 2.11 software, we modeled
several consumer-related exposure scenarios. Different body orientations and age
groups were investigated. Moreover, a number of materials representing different
densities were used, and the exposure calculated using MPPD is compared to the
hazard derived from the overload hypothesis. Conditions leading to macrophage
overload were found for exposures to high particle doses for prolonged times and
repeated exposure. Such conditions are unlikely in the context of regular
consumer exposure. The overload hypothesis assumes the particles to be inert and
biopersistent, a condition that currently lacks a clear regulatory definition and
is valid only for a few selected materials. Furthermore, because of material
specific effects and the possibility of surface adsorption of hazardous
chemicals, nano-objects in propellant sprays remain of concern for consumer
health.
PMID- 26418668
TI - Children (10-12 years age) of women with epilepsy have lower intelligence,
attention and memory: Observations from a prospective cohort case control study.
AB - OBJECTIVE: To compare the cognitive outcome of children of women with epilepsy
(CWE) with matched controls (CWO). METHODS: CWE (10-12 years) under follow up in
Kerala Registry of Epilepsy and Pregnancy (n=190) were evaluated with WISC-IV,
Trail Making Test (TMT), Rey Auditory Verbal Learning Test (RAVLT) and compared
with age and sex matched children of women without epilepsy - CWO (n=149) drawn
from schools in the same region. The dosage was expressed as prescribed daily
dose/daily-defined dose (PDD/DDD) ratio in order to make comparisons. RESULTS:
The Full Scale IQ of CWE (77.9 +/- 14.6) was 8.5 points lower than that of CWO
(86.4 +/- 13.4), which was statistically significant (p=0.001). They performed
lower on TMT Part A & B and RAVLT. The FSIQ mean +/- SD; PDD/DDD ratio and number
of monotherapy exposure for different anti-epileptic drugs were phenobarbital:
(74.5 +/- 14; 1.1 +/- 0.8; 22), valproate: (82.8 +/- 12.4; 0.3 +/- 0.1; 36),
carbamazepine: (82.2 +/- 13.9; 0.6 +/- 0.3; 41), phenytoin: (82.6 +/- 13.5; 0.8+/
0.3; 11). The FSIQ for those exposed to phenobarbital was significantly (p=0.01)
lower than others. The significant predictors of FSIQ differed at lower and
higher ends of its spectrum. These predictors were low body mass index and low
maternal education for FSIQ<80 and low maternal education, low maternal IQ and
high anti-epileptic drug dosage for FSIQ<86. High anti-epileptic drug dosage, low
maternal IQ, and low paternal education were the predictors for FSIQ<92.
SIGNIFICANCE: The IQ, attention and memory were significantly lower for 10-12
year old CWE when compared to CWO. The important predictors of low FSIQ were
antiepileptic drug dosage, maternal IQ, and parental education.
PMID- 26418669
TI - Prenatal Organophosphorus Pesticide Exposure and Child Neurodevelopment at 24
Months: An Analysis of Four Birth Cohorts.
AB - BACKGROUND: Organophosphorus pesticides (OPs) are used in agriculture worldwide.
Residential use was common in the United States before 2001. OBJECTIVES: We
conducted a pooled analysis of four birth cohorts (children's centers; n = 936)
to evaluate associations of prenatal exposure to OPs with child development at 24
months. METHODS: Using general linear models, we computed site-specific and
pooled estimates of the association of total dialkyl (SigmaDAP), diethyl
(SigmaDEP), and dimethylphosphate (SigmaDMP) metabolite concentrations in
maternal prenatal urine with mental and psychomotor development indices (MDI/PDI)
and evaluated heterogeneity by children's center, race/ethnicity, and PON1
genotype. RESULTS: There was significant heterogeneity in the center-specific
estimates of association for SigmaDAP and SigmaDMP and the MDI (p = 0.09, and p =
0.05, respectively), as well as heterogeneity in the race/ethnicity-specific
estimates for SigmaDAP (p = 0.06) and SigmaDMP (p = 0.02) and the MDI. Strong MDI
associations in the CHAMACOS population per 10-fold increase in SigmaDAP (beta =
4.17; 95% CI: -7.00, -1.33) and SigmaDMP (beta = -3.64; 95% CI: -5.97, -1.32)
were influential, as were associations among Hispanics (beta per 10-fold increase
in SigmaDAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative
associations of SigmaDAP and SigmaDEP with the 24-month MDI for carriers of the
192Q PON1 allele, particularly among blacks and Hispanics. CONCLUSIONS: Data
pooling was complicated by center-related differences in subject characteristics,
eligibility, and changes in regulations governing residential use of OPs during
the study periods. Pooled summary estimates of prenatal exposure to OPs and
neurodevelopment should be interpreted with caution because of significant
heterogeneity in associations by center, race/ethnicity, and PON1 genotype.
Subgroups with unique exposure profiles or susceptibilities may be at higher risk
for adverse neurodevelopment following prenatal exposure. CITATION: Engel SM,
Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, Barr DB, Yolton K,
Vedar MG, Xu Y, Hornung RW, Wetmur JG, Chen J, Holland NT, Perera FP, Whyatt RM,
Lanphear BP, Eskenazi B. 2016. Prenatal organophosphorus pesticide exposure and
child neurodevelopment at 24 months: an analysis of four birth cohorts. Environ
Health Perspect 124:822-830; http://dx.doi.org/10.1289/ehp.1409474.
PMID- 26418670
TI - Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection:
NORDynamIC trial and real-life experience.
AB - OBJECTIVE: Interferon-free therapy for hepatitis C virus (HCV) infection is
costly, and therefore patients with advanced fibrosis are prioritized. Although
coupled with considerable side effects, a large proportion of genotype 2/3
infected patients achieve a sustained virological response (SVR) following
interferon-based therapy. The present study evaluates experimental clinical trial
and verifying real-life data with the aim of identifying patients with a high
likelihood of favorable outcome following short interferon-based treatment.
MATERIAL AND METHODS: The impact of established response predictors, e.g. age,
ITPA and IL28B genetic variants, IP-10, liver histopathology and early viral
kinetics on outcome was evaluated among HCV genotype 2/3 infected patients
enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish
and Swedish real-life genotype 2/3 infected patients treated for 12-16 weeks in
accordance with national guidelines. RESULTS: In the NORDynamIC trial, age < 40
years or achieving HCV RNA < 1000 IU/mL day 7 were highly predictive of favorable
outcome following 12 weeks therapy. Among 255 Finnish real-life patients below
the age of 40 years treated for 12 weeks with interferon and ribavirin, 87% of
HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among
117 Swedish real-life patients treated for 12-16 weeks, 97% of HCV genotype 2 and
94% of genotype 3 infected achieved SVR. CONCLUSIONS: Short interferon-based
therapy offers a high likelihood of achieving SVR for selected HCV genotype 2/3
infected patients, and is an acceptable option given that a thorough discussion
of the side effects is provided prior to initiation.
PMID- 26418671
TI - Ontogenetic changes in contribution of calcium sensitization and calcium entry to
blood pressure maintenance of Wistar-Kyoto and spontaneously hypertensive rats.
AB - BACKGROUND: Altered calcium sensitization (mediated by RhoA/Rho-kinase pathway)
and enhanced calcium entry through L-type voltage-dependent calcium channels (L
VDCCs) participate in blood pressure (BP) maintenance of adult spontaneously
hypertensive rats (SHRs). This study aimed to evaluate ontogenetic changes of
these two pathways in BP control of SHR and Wistar-Kyoto (WKY) aged 3, 5, 7, 13,
26 and 42 weeks. METHODS: BP response to acute administration of Rho-kinase
inhibitor fasudil or L-VDCC blocker nifedipine and the expression of particular
components of RhoA/Rho-kinase pathway were determined in young and adult animals.
RESULTS: Fasudil-induced BP reduction was attenuated in young SHR compared with
WKY, but was enhanced in adult SHR. In contrast, BP response to nifedipine was
similar in 3-week-old SHR and WKY and it was augmented with age in SHR but not in
WKY. Consequently, the ratio between fasudil-induced and nifedipine-induced BP
changes was lower in all age groups of SHR compared with WKY. Fasudil effects on
contractility of isolated arteries were attenuated in young but not in adult SHR.
mRNA expression of selected Rho-GEFs (Arhgef1, Arhgef11 and Arhgef12) was
decreased only in adult SHR, whereas p63RhoGEF and CPI-17 expression was reduced
in both age groups of SHR. Active RhoA and phosphorylated CPI-17 were increased
in adult but not in young SHR. CONCLUSION: The importance of RhoA/Rho-kinase
pathway for BP/vascular tone control is attenuated in SHR from prehypertensive
stages. Enhanced RhoA activation and/or CPI-17 phosphorylation might be
counteracted by reduced expression of upstream activators of Rho-kinase (Rho
GEFs) together with lower expression of CPI-17 (in downstream cascade of Rho
kinase).
PMID- 26418672
TI - pi-Conjugated Microporous Polymer Films: Designed Synthesis, Conducting
Properties, and Photoenergy Conversions.
AB - Conjugated microporous polymers are a unique class of polymers that combine
extended pi-conjugation with inherent porosity. However, these polymers are
synthesized through solution-phase reactions to yield insoluble and unprocessable
solids, which preclude not only the evaluation of their conducting properties but
also the fabrication of thin films for device implementation. Here, we report a
strategy for the synthesis of thin films of pi-conjugated microporous polymers by
designing thiophene-based electropolymerization at the solution-electrode
interface. High-quality films are prepared on a large area of various electrodes,
the film thickness is controllable, and the films are used for device
fabrication. These films are outstanding hole conductors and, upon incorporation
of fullerenes into the pores, function as highly efficient photoactive layers for
energy conversions. Our film strategy may boost the applications in
photocatalysis, energy storage, and optoelectronics.
PMID- 26418674
TI - BRAF and RAS Mutations in Sporadic and Secondary Pyogenic Granuloma.
AB - Pyogenic granuloma (PG) is a common benign vascular skin lesion presenting as a
rapidly growing angiomatous papule. The pathogenesis of most sporadic PG and PG
associated with port wine stains (PWS) remains elusive. We report that of 10 PG
secondarily arisen on a PWS, 8 showed a BRAF c.1799T>A (p.(Val600Glu)) and 1 a
NRAS c.182A>G (p.(Gln61Arg)) mutation. The GNAQ c.548G>A mutation was identified
in the PG and in the respective underlying PWS, indicating that the PG originate
from cells of the PWS. In contrast to PG, twelve papulonodular lesions, which had
developed in the PWS of seven patients, showed a RAS and BRAF wildtype status. In
sporadic PG we identified the BRAF c.1799T>A mutation in 3/25, a BRAF c.1391G>A
mutation in 1/25 and a KRAS c.37G>C mutation in 1/25. Mutation-specific
immunohistochemical detection of BRAF p.(Val600Glu) confirmed endothelial cells
as carriers of the mutation in secondary and sporadic PG. Our study identifies
the BRAF c.1799T>A mutation as a major driver mutation in the pathogenesis of
particularly secondary PG. These data shed light on the hitherto undetermined
genetic basis of PG and classify PG as a benign neoplasm.Journal of Investigative
Dermatology accepted article preview online, 29 September 2015.
doi:10.1038/jid.2015.376.
PMID- 26418677
TI - The Impact of a 24 Month Housing First Intervention on Participants' Body Mass
Index and Waist Circumference: Results from the At Home / Chez Soi Toronto Site
Randomized Controlled Trial.
AB - Research suggests that individuals experiencing homelessness have high rates of
overweight and obesity. Unhealthy weights and homelessness are both associated
with increased risk of poor health and mortality. Using longitudinal data from
575 participants at the Toronto site of the At Home/Chez Soi randomized
controlled trial, we investigate the impact of receiving a Housing First
intervention on the Body Mass Index (BMI) and waist circumference of participants
with moderate and high needs for mental health support services. The ANCOVA
results indicate that the intervention resulted in no significant change in BMI
or waist circumference from baseline to 24 months. The findings suggest a need
for a better understanding of factors contributing to overweight, obesity, and
high waist circumference in populations who have histories of housing precarity
and experience low-income in tandem with other concerns such as mental illness
and addictions. TRIAL REGISTRATION: International Standard Randomized Control
Trial Number Register ISRCTN42520374.
PMID- 26418679
TI - Adding Spice to the Slog: Humanities in Medical Training.
AB - Writing from personal experience, physician and author Danielle Ofri asks what
evidence is needed to justify trying to humanize medical training via the power
of literature.
PMID- 26418678
TI - Do Instructional Videos on Sputum Submission Result in Increased Tuberculosis
Case Detection? A Randomized Controlled Trial.
AB - OBJECTIVE: We examined the effect of an instructional video about the production
of diagnostic sputum on case detection of tuberculosis (TB), and evaluated the
acceptance of the video. TRIAL DESIGN: Randomized controlled trial. METHODS: We
prepared a culturally adapted instructional video for sputum submission. We
analyzed 200 presumptive TB cases coughing for more than two weeks who attended
the outpatient department of the governmental Municipal Hospital in Mwananyamala
(Dar es Salaam, Tanzania). They were randomly assigned to either receive
instructions on sputum submission using the video before submission (intervention
group, n = 100) or standard of care (control group, n = 100). Sputum samples were
examined for volume, quality and presence of acid-fast bacilli by experienced
laboratory technicians blinded to study groups. RESULTS: Median age was 39.1
years (interquartile range 37.0-50.0); 94 (47%) were females, 106 (53%) were
males, and 49 (24.5%) were HIV-infected. We found that the instructional video
intervention was associated with detection of a higher proportion of
microscopically confirmed cases (56%, 95% confidence interval [95% CI] 45.7
65.9%, sputum smear positive patients in the intervention group versus 23%, 95%
CI 15.2-32.5%, in the control group, p <0.0001), an increase in volume of
specimen defined as a volume >=3ml (78%, 95% CI 68.6-85.7%, versus 45%, 95% CI
35.0-55.3%, p <0.0001), and specimens less likely to be salivary (14%, 95% CI 7.9
22.4%, versus 39%, 95% CI 29.4-49.3%, p = 0.0001). Older age, but not the HIV
status or sex, modified the effectiveness of the intervention by improving it
positively. When asked how well the video instructions were understood, the
majority of patients in the intervention group reported to have understood the
video instructions well (97%). Most of the patients thought the video would be
useful in the cultural setting of Tanzania (92%). CONCLUSIONS: Sputum submission
instructional videos increased the yield of tuberculosis cases through better
quality of sputum samples. If confirmed in larger studies, instructional videos
may have a substantial effect on the case yield using sputum microscopy and also
molecular tests. This low-cost strategy should be considered as part of the
efforts to control TB in resource-limited settings. TRIAL REGISTRATION: Pan
African Clinical Trials Registry PACTR201504001098231.
PMID- 26418680
TI - Infant Growth and the Occurrence of Developmental Defects of Enamel in 12-Year
Olds.
AB - BACKGROUND/AIMS: To investigate the association between birth weight and infant
growth during the first year of life and the occurrence of developmental defects
of enamel (DDE) in permanent dentition. METHODS: A random sample of 668 12-year
old students was recruited from a birth cohort. Permanent incisors and first
molars were clinically examined for DDE using the modified FDI (DDE) index.
Multivariable negative binomial regression was used to examine the association of
growth trajectory (five categories) from birth to 12 months with the occurrence
of DDE (any defects, demarcated opacities, diffuse opacities, and hypoplasia) in
the permanent dentition. RESULTS: The response rate was 76.9% (n = 514). Four
hundred and eighty-five children had complete records of growth- and health
related data. In the unadjusted model, infants who had birth weights closer to
the WHO average and rapid growth were more likely to have 'demarcated opacities'
(p < 0.05), and the first 3 months of life was the 'critical period' to develop
'demarcated opacities' in permanent dentition. However, after adjusting for the
confounders (gender, gestational age, mode of delivery, type of feeding, parental
education, and health status), significant association with the occurrence of
'demarcated opacities' (p < 0.05) remained only for the children of trajectory V
(heavier birth weights and rapid growth); no 'critical period' was found to be
significantly associated with DDE. CONCLUSIONS: Infants with heavy birth weight
and rapid growth during the first year of life were more vulnerable to the
occurrence of DDE in terms of demarcated opacities in their permanent dentition.
PMID- 26418682
TI - Introduction to the Special Issue.
PMID- 26418681
TI - Multi-Etiological Nature of Tuberculosis-Like Lesions in Condemned Pigs at the
Slaughterhouse.
AB - Tuberculosis-like lesions (TBL) in pigs have been associated with microorganisms
other than mycobacteria. In this work a histopathological and microbiological
evaluation of TBL in pigs is shown. A total of 352 samples belonging to 171 pigs
totally condemned at slaughterhouse due to generalized TBL were sampled and
selected for analysis. Pyogranulomatous (56.2%) and granulomatous lesions (20.2%)
were observed in all analysed organs. Most of the granulomas observed in both
lymph nodes and lungs belonged to more advanced stages of development (stages III
and IV) whereas in the liver and the spleen most of lesions belonged to
intermediate stages (stages II and III). Different microorganisms were
simultaneously detected from TBL in the 42.7% of the animals. Mycobacterium
tuberculosis complex (MTC) (38%), coryneform bacteria (40.3%) and streptococci
(28.1%) were the main groups of microorganisms detected after bacteriological
analysis, with Trueperella pyogenes and Streptococcus suis as the most frequently
isolated species. Mycobacteria belonging to MTC were the most frequently detected
pathogens in granulomatous and pyogranulomatous lesions in submandibular lymph
nodes (32.7%) and coryneform bacteria were the microorganisms more frequently
isolated from lungs (25.9%) and spleen samples (37.2%). These results may provide
new insights into the pathogenesis and diagnosis of this pathology. The
importance of coryneform bacteria and streptococci in such processes must be
evaluated in future studies.
PMID- 26418683
TI - Superficial Head and Neck Anatomy for Dermatologic Surgery: Critical Concepts.
AB - BACKGROUND: Thorough understanding of head and neck anatomy is useful and
necessary for dermatologic surgery. OBJECTIVE: To highlight pertinent head and
neck anatomic structures that are encountered during dermatologic surgery and
correlate these with common surgical problems. METHODS: Important anatomic
structures and regional cutaneous anatomy are discussed and illustrated. RESULTS:
Several important anatomic structures exist within the head and neck that can
influence surgical outcomes. CONCLUSION: Anatomic knowledge is helpful to the
dermatologic surgeon to optimize reconstructive outcomes.
PMID- 26418684
TI - Secondary Intention Healing and Purse-String Closures.
AB - BACKGROUND: Secondary intention healing and purse-string closures are simple but
extremely useful methods for the dermatologic surgeon to master. OBJECTIVE: To
review the literature on the use of these two types of closures and offer
recommendations based on our collective experiences. METHODS: A literature review
was performed using the terms "secondary intention healing" and "purse-string
closure." The evidence and recommendations from the resultant references were
summarized in our article and synthesized with our own experiences. RESULTS:
Twenty-eight sources were cited overall with fifteen related to secondary
intention healing, eleven pertaining to purse-string closures, and one
randomized, blind clinical trial comparing the two modalities. CONCLUSION: The
art of dermatologic surgery often requires a tailored approach to the patient and
can involve a spectrum of closures, from the simplest to most complex. This
variety not only provides more reconstruction options, but are also necessary to
keep dermatologic surgery cost-effective. Certain locations or situations are
more amenable for these two types of closures than others. The use of secondary
intention healing, either alone or in conjunction with purse-string closures,
should be in every dermatologic surgeon's armamentarium.
PMID- 26418685
TI - Suture Products and Techniques: What to Use, Where, and Why.
AB - BACKGROUND: There are an increasing number of wound closure materials and
suturing techniques described in the dermatologic and surgery literature. A
dermatologic surgeon's familiarity with these materials and techniques is
important to supplement his or her already established practices and improve
surgical outcomes. OBJECTIVE: To perform a thorough literature review of wound
closure materials (sutures, tissue adhesives, surgical tape, and staples) and
suturing techniques and to outline how and when to use them. MATERIALS AND
METHODS: A literature review was conducted using PubMed and other online search
engines. Keywords searched included suture, tissue adhesive, tissue glue,
surgical tape, staples, dermatologic suturing, and suturing techniques. RESULTS:
Numerous articles outline the utility of various sutures, surgical adhesives,
surgical tape, and staples in dermatologic surgery. In addition, there are
various articles describing classic and novel suturing techniques along with
their specific uses in cutaneous surgery. CONCLUSION: Numerous factors must be
considered when choosing a wound closure material and suturing technique. These
include wound tension, desire for wound edge eversion/inversion, desired
hemostasis, repair type, patient's ability to care for the wound and return for
suture removal, skin integrity, and wound location. Careful consideration of
these factors and proper execution of suturing techniques can lead to excellent
cosmetic results.
PMID- 26418686
TI - Undermining and Hemostasis.
AB - BACKGROUND: Undermining and hemostasis are basic surgical techniques that can
have a significant impact on surgical outcomes. OBJECTIVE: To review the
mechanisms and techniques of undermining and hemostasis, with an emphasis on the
advantages and limitations of each modality. MATERIALS AND METHODS: The PubMed
database was searched for articles with the keywords "undermining," "hemostasis,"
and "electrosurgery." RESULTS: Whether performing blunt, sharp, or
electrosurgical techniques, undermining at the appropriate depth and width is
necessary for tissue movement during closures. Both excessive and inadequate
undermining can compromise surgical healing. Surgical hemostasis techniques
include pressure, suture ligation, topical hemostatic agents, and electrosurgery.
Dermatologic surgeons should select the appropriate amount and type of hemostasis
for each procedure. Particular care should be taken in performing electrosurgery,
given the potential for complications. CONCLUSION: Understanding and optimizing
hemostasis and undermining will allow dermatologic surgeons to execute complex
closures with minimal complications.
PMID- 26418687
TI - Optimizing Design and Execution of Linear Reconstructions on the Face.
AB - BACKGROUND: Linear closure (LC) is the most common reconstructive design for
cutaneous defects. Successful performance of a LC is dependent on both
appropriate surgical planning and technical execution. OBJECTIVE: To review the
design and execution of LCs on the face. MATERIALS AND METHODS: A systematic
evaluation of LCs is provided to guide a logical approach for the repair of
cutaneous facial defects. RESULTS: Reproducibly excellent aesthetic and
functional results may be achieved with strategies that reduce incisional
tension, preserve free margin position, and restore skin contour. Cosmetic unit
borders and relaxed skin tension lines may be used to further camouflage facial
scars. A comprehensive knowledge of facial anatomy, biomechanical properties of
the skin, and incisional tension vectors facilitates correct preoperative
planning and intraoperative technique. CONCLUSION: Proper design and execution of
LCs allow for enhanced cosmesis and permit the cutaneous surgeon to progress to
more technically advanced surgical procedures such as cutaneous flaps.
PMID- 26418688
TI - Nonfacial Reconstructive Techniques.
AB - BACKGROUND: Nonfacial reconstruction encompasses several anatomic locations with
varied topography, skin quality, and tissue reservoirs. Patients also have varied
mobility concerns and wound care needs when managing wounds in these areas.
MATERIALS AND METHODS: This article includes techniques and approaches from the
dermatologic surgery, plastic surgery, and podiatric surgery literature in an
effort to provide a comprehensive overview of the subject matter. RESULTS AND
CONCLUSION: Functionally and esthetically acceptable reconstructions of nonfacial
surgical wounds can be accomplished with a variety of techniques based on the
characteristics of the wound and unique needs of the patient.
PMID- 26418689
TI - Advancement Flaps.
AB - BACKGROUND: Advancement flaps are random-pattern flaps frequently used in the
reconstruction of surgical defects on the face after the removal of skin cancer.
Proper design and meticulous execution is crucial in achieving reproducible
esthetic results. OBJECTIVE: To review the design and execution of advancement
flaps in facial reconstruction. MATERIALS AND METHODS: A review of the literature
on the use of advancement flaps in facial reconstruction was performed and
curated with the authors' experience. CONCLUSION: Many factors come into play
when using local flaps to reconstruct surgical defects on the face. Close
attention must be given to the tissue surrounding the surgical defect and any
free margin in the area. Designing the flap closure lines along cosmetic unit
junctions and or relaxed skin tension lines, preserving both the form and
function of the surrounding structures, and using excellent surgical techniques
during the closure will all together help in providing reproducibly outstanding
results.
PMID- 26418690
TI - Rotation Flaps-Principles and Locations.
AB - BACKGROUND: The rotation flap is a classic method of tissue rearrangement. It is
a simple yet effective tool for recruiting tissue from areas of laxity and
redirecting vectors of tension to reconstruct wounds not amenable to primary
closure. OBJECTIVE: This article presents the basic design principles and
specific applications of the rotation flap in dermatologic surgery. METHODS: A
Medline search of articles describing rotation flaps published prior to April 1,
2015 was performed, and several prominent texts in dermatologic surgery were
reviewed. RESULTS: Information gathered from the above sources is combined with
the clinical experience of the author and editors to present surgeons with a
guide for planning and executing various rotation flaps. CONCLUSIONS: Mastering
the technique of the rotation flap will allow a surgeon to repair a wide variety
of cutaneous defects.
PMID- 26418691
TI - Transposition Flaps: Principles and Locations.
AB - BACKGROUND: Transposition flaps are frequently used to repair defects of the head
and neck after tumor extirpation with Mohs micrographic surgery. OBJECTIVE: To
review the basic principles underlying single-stage transposition flaps and also
their utility relative to location on the head and neck. MATERIALS AND METHODS: A
review of the literature on transposition flaps was performed with specific
reference to the principles of single-stage transposition flaps, including
rhomboid flaps and their variations, multilobed flaps, and the locations where
transposition flaps are frequently executed on the head and neck. RESULTS:
Numerous articles have been written with regard to the techniques for designing
and executing transposition flaps. The primary advantages of transposition flaps
include less undermining as compared to large sliding flaps and the superior
ability to displace tension away from the defect and from free margins. Optimal
cosmesis with these flaps can be achieved with appropriate sizing of flaps (or
lobes), appropriate undermining, and meticulous suturing. CONCLUSION: The
versatility of transposition flaps makes them optimal for repair of defects on
the head and neck and utilization of the outlined key principles and techniques
aid in achieving an aesthetic result.
PMID- 26418692
TI - Best Reconstructive Techniques: Improving the Final Scar.
AB - BACKGROUND: Abnormal cutaneous scarring is due to excessive growth of fibrous
tissue in response to traumatic or iatrogenic tissue injury and may adversely
affect a patient's quality of life. The success of a surgical procedure is often
tied to the cosmetic outcome. OBJECTIVES: To provide a synthesis of available
literature and provide guidelines for the management of cutaneous scars with
laser technology. MATERIALS AND METHODS: An extensive review of the medical
literature was conducted to assess optimal treatment methods for cutaneous scars
based on scar features, location, and skin phototype. Recommendations and
algorithms were described based on this review and our current clinical
experience. RESULTS: Combination therapy with laser and non-laser modalities
offers a safe and effective method for scar revision. CONCLUSION: Armed with an
understanding of relevant available therapies, skillful dermatologic surgeons may
drastically improve the final scar cosmesis. This review discusses current and
emerging laser therapy approaches to scar revision.
PMID- 26418695
TI - Simulation design for microalgal protein optimization.
AB - A method for designing the operating parameters (surface light intensity,
operating temperature and agitation rate) was proposed for microalgal protein
production. Furthermore, quadratic model was established and validated (R(2) >
0.90) with experimental data. It was recorded that temperature and agitation rate
were slightly interdependent. The microalgal protein performance could be
estimated using the simulated experimental setup and procedure developed in this
study. The results also showed a holistic approach for opening a new avenue on
simulation design for microalgal protein optimization.
PMID- 26418693
TI - KCa3.1-Dependent Hyperpolarization Enhances Intracellular Ca2+ Signaling Induced
by fMLF in Differentiated U937 Cells.
AB - Formylated peptides are chemotactic agents generated by pathogens. The most
relevant peptide is fMLF (formyl-Met-Leu-Phe) which participates in several
immune functions, such as chemotaxis, phagocytosis, cytokine release and
generation of reactive oxygen species. In macrophages fMLF-dependent responses
are dependent on both, an increase in intracellular calcium concentration and on
a hyperpolarization of the membrane potential. However, the molecular entity
underlying this hyperpolarization remains unknown and it is not clear whether
changes in membrane potential are linked to the increase in intracellular Ca2+.
In this study, differentiated U937 cells, as a macrophage-like cell model, was
used to characterize the fMLF response using electrophysiological and Ca2+
imaging techniques. We demonstrate by means of pharmacological and molecular
biology tools that fMLF induces a Ca2+-dependent hyperpolarization via activation
of the K+ channel KCa3.1 and thus, enhancing fMLF-induced intracellular Ca2+
increase through an amplification of the driving force for Ca2+ entry.
Consequently, enhanced Ca2+ influx would in turn lengthen the hyperpolarization,
operating as a positive feedback mechanism for fMLF-induced Ca2+ signaling.
PMID- 26418696
TI - Fiber-optic Monitoring of Spinal Cord Hemodynamics in Experimental Aortic
Occlusion.
AB - BACKGROUND: Spinal cord ischemia occurs frequently during thoracic aneurysm
repair. Current methods based on electrophysiology techniques to detect ischemia
are indirect, non-specific, and temporally slow. In this article, the authors
report the testing of a spinal cord blood flow and oxygenation monitor, based on
diffuse correlation and optical spectroscopies, during aortic occlusion in a
sheep model. METHODS: Testing was carried out in 16 Dorset sheep. Sensitivity in
detecting spinal cord blood flow and oxygenation changes during aortic occlusion,
pharmacologically induced hypotension and hypertension, and physiologically
induced hypoxia/hypercarbia was assessed. Accuracy of the diffuse correlation
spectroscopy measurements was determined via comparison with microsphere blood
flow measurements. Precision was assessed through repeated measurements in
response to pharmacologic interventions. RESULTS: The fiber-optic probe can be
placed percutaneously and is capable of continuously measuring spinal cord blood
flow and oxygenation preoperatively, intraoperatively, and postoperatively. The
device is sensitive to spinal cord blood flow and oxygenation changes associated
with aortic occlusion, immediately detecting a decrease in blood flow (-65 +/-
32%; n = 32) and blood oxygenation (-17 +/- 13%, n = 11) in 100% of trials.
Comparison of spinal cord blood flow measurements by the device with microsphere
measurements led to a correlation of R = 0.49, P < 0.01, and the within-sheep
coefficient of variation was 9.69%. Finally, diffuse correlation spectroscopy is
temporally more sensitive to ischemic interventions than motor-evoked potentials.
CONCLUSION: The first-generation spinal fiber-optic monitoring device offers a
novel and potentially important step forward in the monitoring of spinal cord
ischemia.
PMID- 26418697
TI - Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non
depolarizing Neuromuscular-blocking Agents.
AB - BACKGROUND: The authors evaluated the comparative effectiveness of calabadion 2
to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and
inactivation. METHODS: The dose-response relationship of drugs to reverse
vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was
evaluated in vitro (competition binding assays and urine analysis), ex vivo (n =
34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps
femoris muscle of the rat). Cumulative dose-response curves of calabadions,
neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In
living rats, the authors studied the dose-response relationship of the test drugs
to reverse deep block under physiologic conditions, and they measured the amount
of calabadion 2 excreted in the urine. RESULTS: In vitro experiments showed that
calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4
* 10 M and Ka = 3.8 * 10 M-). The results of urine analysis (proton nuclear
magnetic resonance), competition binding assays, and ex vivo study obtained in
the absence of metabolic deactivation are in accordance with an 1:1 binding ratio
of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2
dose-dependently and rapidly reversed all NMBAs tested. The molar potency of
calabadion 2 to reverse vecuronium and rocuronium was higher compared with that
of sugammadex. Calabadion 2 was eliminated renally and did not affect blood
pressure or heart rate. CONCLUSIONS: Calabadion 2 reverses NMB induced by
benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster
than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in
rats.
PMID- 26418698
TI - Survival after Perioperative Cardiopulmonary Resuscitation: Providing an Evidence
Base for Ethical Management of Do-not-resuscitate Orders.
AB - Automatic suspension of do-not-resuscitate (DNR) orders during general anesthesia
does not sufficiently address a patient's right to self-determination and is a
practice still observed among anesthesiologists today. To provide an evidence
base for ethical management of DNR orders during anesthesia and surgery, the
authors performed a systematic review of the literature to quantify the survival
after perioperative cardiopulmonary resuscitation (CPR). Results show that the
probability of surviving perioperative CPR ranged from 32.0 to 55.7% when
measured within the first 24 h after arrest with a neurologically favorable
outcome expectancy between 45.3 and 66.8% at follow-up, which suggests a viable
survival of approximately 25%. Because CPR generally proves successful in less
than 15% of out-of-hospital cardiac arrests, the altered outcome probabilities
that the conditions in the operating room bring on warrant reevaluation of DNR
orders during the perioperative period. By preoperatively communicating the
evidence to patients, they can make better informed decisions while reducing the
level of moral distress that anesthesiologists may experience when certain
patients decide to retain their DNR orders.
PMID- 26418699
TI - Evaluation of Vancomycin Prediction Methods Based on Estimated Creatinine
Clearance or Trough Levels.
AB - BACKGROUND: The aim of this study was to investigate whether vancomycin clearance
(CLva) can be adequately predicted with CLva prediction methods. Additionally,
other covariates influencing the CLva were investigated and predictivity of
monitoring of only trough levels to 24-hour area under the curve (AUC24) was
evaluated. METHODS: Routine vancomycin plasma levels were measured with a
fluorescence polarization immunoassay. Pharmacokinetic (PK) parameters of
individual patients, that is, CLva and volume of distribution, were determined
with maximum a posteriori Bayesian estimation. CLva was calculated with the 3
prediction methods, which are solely based on creatinine clearance (CLcr)
estimated with Cockcroft and Gault formula and was compared with the calculated
CLva with maximum a posteriori Bayesian estimation. Prediction errors were
calculated. Correlations between CLva and CLcr, creatinine, age, weight, sex, and
neutropenia were made. Furthermore, correlations between trough levels and AUC24
were evaluated. RESULTS: A total of 171 patients were included. Prediction errors
and absolute prediction errors of the 3 methods ranged from 28% to 80% and 39% to
83%, respectively. In the multivariate analysis, CLva was significantly
associated with CLcr, creatinine, age, weight, sex, and neutropenia. Linear
correlation between AUC24 and trough levels was R(2) 0.38. CONCLUSIONS: Large
prediction errors make the CLva algorithms based on estimated plasma CLcr
unsuitable for use in patient care. Additionally, other factors, which are not
accounted for in the current algorithms, influence the CLva individually. Owing
to low association of AUC24 and trough levels, the AUC24 cannot be predicted with
through levels. For a reliable AUC24 guided vancomycin dosing, therapeutic drug
monitoring is necessary.
PMID- 26418700
TI - Risperidone and Venlafaxine Metabolic Ratios Strongly Predict a CYP2D6 Poor
Metabolizing Genotype.
AB - PURPOSE: To investigate the predictive value of the risperidone and venlafaxine
metabolic ratios and CYP2D6 genotype. METHODS: The determination of risperidone,
9-hydroxyrisperidone, and venlafaxine, O-desmethylvenlafaxine, N
desmethylvenlafaxine and CYP2D6 genotype was performed in 425 and 491 patients,
respectively. The receiver operator characteristic method and the area under the
receiver operator characteristic curve were used to illustrate the predictive
value of risperidone metabolic ratio for the individual CYP2D6 genotype. To
evaluate the proposed cutoff levels of >1 to identify individuals with a poor
CYP2D6 genotype, the sensitivity, specificity, positive predictive values, and
negative predictive values were calculated. RESULTS: Area under the receiver
operator characteristic curve to predict poor metabolizers for risperidone/9
hydroxyrisperidone and N-desmethylvenlafaxine/O-desmethylvenlafaxine ratios was
93% and 99%, respectively. The sensitivity, specificity, positive predictive
value, and negative predictive value (confidence interval) of a risperidone/9
hydroxyrisperidone ratio >1 to predict a CYP2D6 poor metabolizer genotype were
91% (76%-97%), 86% (83%-89%), 35% (26%-46%), and 99% (97%-100%), respectively.
The corresponding measures for N-desmethylvenlafaxine/O-desmethylvenlafaxine were
93% (76%-97%), 87% (83%-89%), 40% (32%-51%), and 99% (98%-100%). CONCLUSIONS:
Risperidone/9-hydroxyrisperidone and N-desmethylvenlafaxine/O
desmethylvenlafaxine metabolic ratios >1 strongly predict individuals with poor
metabolizer genotype, which could guide psychotropic drug treatment to avoid
adverse drug reactions and to increase their therapeutic efficacy in patients
prescribed these drugs.
PMID- 26418701
TI - Nuclear Factor of Activated T Cells-Regulated Gene Expression as Predictive
Biomarker of Personal Response to Calcineurin Inhibitors.
AB - BACKGROUND: Calcineurin inhibitors (CNIs) represent the most widely used
immunosuppressive agents in kidney transplantation. Both CNIs show a narrow
therapeutic window; thus, monitoring is necessary to balance efficacy and
toxicity. Several approaches have been undertaken to measure the biological
effects of CNI-based immunosuppression. METHODS: A quantitative analysis of gene
expression was established to calculate the functional effects of calcineurin
inhibition, the assessment of nuclear factor of activated T cells (NFAT)
regulated gene expression. This assay is based on the quantitative analysis of
interleukin-2, interferon-gamma, and granulocyte macrophage colony-stimulating
factor gene expression in whole blood samples collected at the time cyclosporine
A/tacrolimus troughs (C0) and 2 hours after oral uptake (C2). RESULTS: In this
comprehensive review, analytical aspects of the assay and also clinical benefits
and limitations are presented and discussed. Several observational studies
underline the beneficial effect of NFAT-regulated gene expression as biomarker of
personal response on CNI therapy, especially in infectious complications,
malignancies, and acute rejection episodes. Data are more comprehensive in
cyclosporine A compared with tacrolimus therapy. However, results on prospective
interventional studies are sparse. A randomized controlled study evaluating the
opportunity for NFAT-guided immunosuppression is ongoing. CONCLUSIONS: NFAT
regulated gene expression is a promising biomarker in CNI therapy concerning
infectious complications, malignancies, and acute rejection. Prospective
interventional studies and randomized controlled studies are ongoing to confirm
the encouraging results.
PMID- 26418703
TI - Graft-Derived Cell-Free DNA as a Marker of Transplant Graft Injury.
AB - Although short-term success after solid organ transplantation is good, long-term
graft and recipient survival are both not satisfactory. Despite therapeutic drug
monitoring (TDM) of immunosuppressive drugs (ISDs), both excessive and
insufficient immunosuppression still do occur. There is a need for new biomarkers
that, when combined with TDM, can be used to provide more effective and less
toxic, personalized immunosuppression to improve long-term survival. Currently
used methods are insufficient to rapidly, cost-effectively, and directly
interrogate graft integrity after solid organ transplantation. However, because
organ transplants are also genome transplants, measurement of graft-derived
circulating cell-free DNA (GcfDNA) has shown promise as a way to improve both
graft and recipient outcomes after solid organ transplantation through the early
detection of severe graft injury, enabling an early intervention. A newly
developed droplet digital polymerase chain reaction (ddPCR) method has advantages
over expensive high-throughput sequencing methods to rapidly quantify GcfDNA
percentages and absolute amounts. This procedure does not require donor DNA and
therefore can be applied to any organ donor/recipient pair. The droplet digital
polymerase chain reaction method allows for the early, sensitive, specific, and
cost-effective direct assessment of graft integrity and can be used to define
individual responses to ISDs including the minimal ISD exposures necessary to
prevent rejection. This is especially important in patients undergoing ISD
switches due to ISD toxicity, infections, or malignancies. Although prospective,
multicenter clinical trials in liver, heart, and kidney transplantation have not
been completed, early results suggest that GcfDNA can be combined with TDM to
guide changes in immunosuppression to provide more effective, and less toxic
treatment. Personalized immunosuppression will shift emphasis in transplantation
from reaction to prevention and could improve outcome at lower health care costs.
PMID- 26418702
TI - Biomarkers in Transplantation--Proteomics and Metabolomics.
AB - Modern multianalyte "omics" technologies allow for the identification of
molecular signatures that confer significantly more information than measurement
of a single parameter as typically used in current medical diagnostics.
Proteomics and metabolomics bioanalytical assays capture a large set of proteins
and metabolites in body fluids, cells, or tissues and, complementing genomics,
assess the phenome. Proteomics and metabolomics contribute to the development of
novel predictive clinical biomarkers in transplantation in 2 ways: they can be
used to generate a diagnostic fingerprint or they can be used to discover
individual proteins and metabolites of diagnostic potential. Much fewer
metabolomics than proteomics biomarker studies in transplant patients have been
reported, and, in contrast to proteomics discovery studies, new lead metabolite
markers have yet to emerge. Most clinical proteomics studies have been discovery
studies. Several of these studies have assessed diagnostic sensitivity and
specificity. Nevertheless, none of these newly discovered protein biomarkers have
yet been implemented in clinical decision making in transplantation. The
currently most advanced markers discovered in proteomics studies in transplant
patients are the chemokines CXCL-9 and CXCL-10, which have successfully been
validated in larger multicenter trials in kidney transplant patients. These
chemokines can be measured using standard immunoassay platforms, which should
facilitate clinical implementation. Based on the published evidence, it is
reasonable to expect that these chemokine markers can help guiding and
individualizing immunosuppressive regimens, may be able to predict acute and
chronic T-cell-mediated and antibody-mediated rejection, and may be useful tools
for risk stratification of kidney transplant patients.
PMID- 26418704
TI - Analytical Aspects of the Implementation of Biomarkers in Clinical
Transplantation.
AB - In response to the urgent need for new reliable biomarkers to complement the
guidance of the immunosuppressive therapy, a huge number of biomarker candidates
to be implemented in clinical practice have been introduced to the transplant
community. This includes a diverse range of molecules with very different
molecular weights, chemical and physical properties, ex vivo stabilities, in vivo
kinetic behaviors, and levels of similarity to other molecules, etc. In addition,
a large body of different analytical techniques and assay protocols can be used
to measure biomarkers. Sometimes, a complex software-based data evaluation is a
prerequisite for appropriate interpretation of the results and for their
reporting. Although some analytical procedures are of great value for research
purposes, they may be too complex for implementation in a clinical setting.
Whereas the proof of "fitness for purpose" is appropriate for validation of
biomarker assays used in exploratory drug development studies, a higher level of
analytical validation must be achieved and eventually advanced analytical
performance might be necessary before diagnostic application in transplantation
medicine. A high level of consistency of results between laboratories and between
methods (if applicable) should be obtained and maintained to make biomarkers
effective instruments in support of therapeutic decisions. This overview focuses
on preanalytical and analytical aspects to be considered for the implementation
of new biomarkers for adjusting immunosuppression in a clinical setting and
highlights critical points to be addressed on the way to make them suitable as
diagnostic tools. These include but are not limited to appropriate method
validation, standardization, education, automation, and commercialization.
PMID- 26418705
TI - Long noncoding RNAs in human disease: emerging mechanisms and therapeutic
strategies.
PMID- 26418706
TI - [In Process Citation].
PMID- 26418707
TI - [In Process Citation].
PMID- 26418708
TI - [In Process Citation].
PMID- 26418709
TI - [Malign hypertension].
PMID- 26418710
TI - [The fasting regime prior to anaesthesia].
AB - In modern anaesthesiology fasting preoperatively has been introduced in order to
minimise the incidence of aspiration to the lungs. Since the 1990's studies have
confirmed the safety of the current fasting regime of six hours for solids and
two hours for fluids. By allowing the intake of carbohydrate-rich fluids until
two hours before induction of anaesthesia, it has been shown that the negative
effects of fasting such as thirst, starvation and anxiety are minimised. In the
future, ultrasound technology might be used to assess the gastric volume prior to
induction of anaesthesia.
PMID- 26418711
TI - [Pharmacological risk differentiation of patients in psychiatry can be used in
medication review].
AB - Based on demands from The Danish Healthcare Quality Programme (DDKM), that all
patients must have a medical review performed, a risk scoring tool has been
developed. The purpose of this tool is to differentiate patients in three groups
to assure that necessary resources are allocated to patients having most
complications. The scoring tool has now been used in more than 5,000 adult
psychiatric patients in Central Denmark Region. The intent of allocating the
necessary resources most effectively, when performing a medical review, seems to
have been attained.
PMID- 26418712
TI - [Pontocerebellar hypoplasia is a rare cause of floppy infant syndrome].
AB - The hypotone neonate, floppy infant, often proves to be a diagnostic challenge,
as the causes of floppy infant syndrome are many and often rare. In this case
story a floppy girl was diagnosed with the rare, autosomal recessive disease
pontocerebellar hypoplasia type I. The tests for the most common causes of floppy
infant syndrome showed nothing abnormal, but an array comparative genomic
hybridization test gave information of loss of heterozygosity. This helped to
narrow the list of plausible diagnoses and eventually led to the diagnosis of
pontocerebellar hypoplasia type I.
PMID- 26418713
TI - [Bullous pemphigoid may also be seen in children].
AB - Bullous pemphigoid is most commonly seen in elderly patients, however, an
increasing number of cases in children have been reported. In this article we
present a case of a five-month-old boy who was admitted with red annular plaques
over his entire body and vesicles and bullae on his hands and feet. Correct
diagnosis was made by skin biopsy and after reviewing the literature high dose
oral steroids therapy (1 mg/kg/day) was successfully initiated. The cause of the
disease remains unknown. With correct treatment the prognosis is good with
documented ten-year follow-up without relapse.
PMID- 26418714
TI - [A historical perspective of Ebola virus].
AB - The 2014 Ebola fever outbreak was the first of its kind in West Africa. This
epidemic, affecting multiple countries, by far exceeded any previous outbreak in
case counts and geographical spread. But Ebola viruses are not new to Africa, as
they have occurred in epidemic proportion in the central part of the continent
since 1976. The objective of this article is to compare previous outbreaks with
the ongoing epidemic in an effort to identify some of the factors which have con
tributed to the size and scope of the existing outbreak.
PMID- 26418715
TI - [Work-related MRSA CC398 carrier status had serious psychosocial consequences to
a farmer].
AB - We describe a case of work-related methicillin-resistant Staphylococcus aureus
(MRSA) CC398 carrier status in a 33-year-old male working at a pig farm. The case
was complicated since his pregnant girlfriend had also MRSA CC398 carrier status.
Although she remained without contact to farm animals the MRSA could not be
eradicated. Conflicting messages from healthcare workers complicated the case and
the psychological consequences became traumatizing to the patient and caused sick
leave and psychotherapy. This case shows the importance of better information of
MRSA CC398-positive patients in the future, especially for MRSA-exposed
occupations.
PMID- 26418716
TI - [Varicella zoster meningitis with associated vasculitis in a two-month post
partum woman].
AB - Reactivation of varicella zoster virus occurs more often in the elderly or
immunocompromised persons. During pregnancy increased anti-inflammatory cellular
response promotes tolerance of foetal antigens. Post-partum a shift towards an
inflammatory response may facilitate the reoccurrence of latent infections.
Varicella-associated vasculitis can lead to ischaemic lesions in the brain. We
report a case of a two-month post-partum woman suffering from headache, nausea,
vomiting, photophobia and radicular pain with varicella zoster meningitis and an
ischaemic lesion in the splenium of corpus callosum.
PMID- 26418717
TI - The Quality of Surgical and Pneumonia Care in Minority-Serving and Racially
Integrated Hospitals.
AB - OBJECTIVE: To explore the association between quality of care for surgical and
pneumonia patients and the racial/ethnic composition of hospitals' patients. DATA
SOURCE: Our primary data were surgical and pneumonia processes of care indicators
from the 2012 Medicare Hospital Compare Data. We merged this data with
information from the 2011 American Hospital Association Annual Survey of
Hospitals. We computed the racial and ethnic composition of hospital patients
using 2008 data from the Healthcare Costs and Utilization Project. STUDY DESIGN:
The sample included 1,198 acute care general hospitals from 11 states: AZ, CA,
FL, IA, MA, MD, NC, NJ, NY, WA, and WI. We compared quality across minority
serving, racially integrated, and majority-white hospitals using unconditional
quantile regression models controlling for hospital and market characteristics.
PRINCIPAL FINDINGS: We found quality differences between the lowest performing
minority-serving, racially integrated, and majority-white hospitals. As we moved
from 10th to 90th quantile, the quality differences between hospitals by
patients' racial composition disappeared. In other words, the best minority
serving and racially integrated hospitals performed as well as the best majority
hospitals. CONCLUSIONS: Efforts to improve quality of care for patients in
minority-serving and racially integrated hospitals should focus on the lowest
performers.
PMID- 26418718
TI - Phospho-kinase profile of colorectal tumors guides in the selection of multi
kinase inhibitors.
AB - Protein kinases play a central role in the oncogenesis of colorectal tumors and
are attractive druggable targets. Detection of activated kinases within a tumor
could open avenues for drug selection and optimization of new kinase inhibitors.
By using a phosphokinase arrays with human colorectal tumors we identified
activated kinases, including the Epidermal Growth Factor Receptor (EGFR),
components of the PI3K/mTOR pathway (AKT and S6), and STAT, among others. A
pharmacological screening with kinase inhibitors against these proteins helped us
to identify a new kinase inhibitor, termed EC-70124 that showed the highest anti
proliferative activity in cell lines. EC-70124 also inhibited cell migration and
biochemical experiments demonstrated its effect targeting the PI3K/mTOR pathway.
This drug also arrested cells at G2/M and induced apoptosis. Experiments in
combination with standard chemotherapy used in the clinical setting indicated a
synergistic effect. EC-70124 also reduced tumor growth in vivo and inhibited pS6
in the implanted tumors. In conclusion, by studying the kinase profile of
colorectal tumors, we identified relevant activated pathways, and a new multi
kinase compound with significant antitumor properties.
PMID- 26418719
TI - PDGF activation in PGDS-positive arachnoid cells induces meningioma formation in
mice promoting tumor progression in combination with Nf2 and Cdkn2ab loss.
AB - The role of PDGF-B and its receptor in meningeal tumorigenesis is not clear. We
investigated the role of PDGF-B in mouse meningioma development by generating
autocrine stimulation of the arachnoid through the platelet-derived growth factor
receptor (PDGFR) using the RCAStv-a system. To specifically target arachnoid
cells, the cells of origin of meningioma, we generated the PGDStv-a mouse
(Prostaglandin D synthase). Forced expression of PDGF-B in arachnoid cells in
vivo induced the formation of Grade I meningiomas in 27% of mice by 8 months of
age. In vitro, PDGF-B overexpression in PGDS-positive arachnoid cells lead to
increased proliferation.We found a correlation of PDGFR-B expression and NF2
inactivation in a cohort of human meningiomas, and we showed that, in mice, Nf2
loss and PDGF over-expression in arachnoid cells induced meningioma malignant
transformation, with 40% of Grade II meningiomas. In these mice, additional loss
of Cdkn2ab resulted in a higher incidence of malignant meningiomas with 60% of
Grade II and 30% of Grade III meningiomas. These data suggest that chronic
autocrine PDGF signaling can promote proliferation of arachnoid cells and is
potentially sufficient to induce meningiomagenesis. Loss of Nf2 and Cdkn2ab have
synergistic effects with PDGF-B overexpression promoting meningioma malignant
transformation.
PMID- 26418720
TI - A nanostructure of functional targeting epirubicin liposomes dually modified with
aminophenyl glucose and cyclic pentapeptide used for brain glioblastoma
treatment.
AB - The objectives of the present study were to develop functional targeting
epirubicin liposomes for transferring drugs across the blood-brain barrier (BBB),
treating glioblastoma, and disabling neovascularization. The studies were
performed on glioblastoma cells in vitro and on glioblastoma-bearing mice. The
results showed that the constructed liposomes had a high encapsulation efficiency
for drugs (>95%), suitable particle size (109 nm), and less leakage in the blood
component-containing system; were significantly able to be transported across the
BBB; and exhibited efficacies in killing glioblastoma cells and in destroying
glioblastoma neovasculature in vitro and in glioblastoma-bearing mice. The action
mechanisms of functional targeting epirubicin liposomes correlated with the
following features: the long circulation in the blood system, the ability to be
transported across the BBB via glucose transporter-1, and the targeting effects
on glioblastoma cells and on the endothelial cells of the glioblastoma
neovasculature via the integrin beta3 receptor. In conclusion, functional
targeting epirubicin liposomes could be used as a potential therapy for treating
brain glioblastoma and disabling neovascularization in brain glioblastomas.
PMID- 26418722
TI - Type I collagen fibrils: an inducer of invadosomes.
PMID- 26418723
TI - Osteogenic differentiation of adipose derived stem cells on high and low aspect
ratio micropatterns.
AB - Adipose derived stem cells (ADSCs) were cultured on collagen-silk fibroin films
with microchannel and micropillar patterns to investigate the effects of cell
morphology changes on osteogenic differentiation. Channel and pillar
micropatterned films were prepared from collagen type I and silk fibroin. While
higher ADSC proliferation profiles were obtained on micropillar blend film,
microchannel blend films, however, caused twice higher aspect ratio and effective
orientation of cells. Alkaline phosphatase activity of ADSCs was several times
higher on microchannel surface when the measured activities were normalized to
cell number. Effective deposition of collagen type I and mineral by the cells
were observed for patterned and unpatterned films, and these extracellular matrix
components were oriented along the axis of the microchannels. In conclusion, the
use of collagen-fibroin blend film with microchannel topography increased the
aspect ratio and alignment of cells significantly, and was also effective in the
differentiation of ADSCs into osteogenic lineage.
PMID- 26418721
TI - IL-13 receptor alpha2 is a negative prognostic factor in human lung cancer and
stimulates lung cancer growth in mice.
AB - IL-13 receptor subunit alpha-2 (IL13Ralpha2) is associated with poor prognosis in
some cancers. However, the role of IL13Ralpha2 in lung cancer remains unknown. We
showed that IL13Ralpha2 overexpression was associated with late stages of disease
progression and shorter disease-free survival (DFS) as well as overall survival
(OS) in resected lung cancer patients. IL13Ralpha2 promoted the migration,
invasion and anoikis resistance of lung cancer cells in vitro. Silencing of
IL13Ralpha2 in lung cancer cells decreased invasion in vitro and lung metastasis
in vivo. IL13Ralpha2 activated phosphatidylinositol 3 kinase (PI3K), Akt, and
transcriptional coactivator with PDZ-binding motif (TAZ). Inhibition of PI3K
attenuated activation of TAZ and its downstream target genes by IL13Ralpha2. We
suggest that inhibition of IL13Ralpha2 is a potential therapeutic approach in
lung cancer.
PMID- 26418724
TI - Atomic Layer Deposition from Dissolved Precursors.
AB - We establish a novel thin film deposition technique by transferring the
principles of atomic layer deposition (ALD) known with gaseous precursors toward
precursors dissolved in a liquid. An established ALD reaction behaves similarly
when performed from solutions. "Solution ALD" (sALD) can coat deep pores in a
conformal manner. sALD offers novel opportunities by overcoming the need for
volatile and thermally robust precursors. We establish a MgO sALD procedure based
on the hydrolysis of a Grignard reagent.
PMID- 26418725
TI - Saturation-transfer effects and longitudinal relaxation times of (31) P
metabolites in fibroglandular breast tissue at 7T.
AB - PURPOSE: To investigate longitudinal relaxation times and saturation-transfer
effects of phosphorous metabolites in breast fibroglandular tissue in vivo with
(31) P MR spectroscopy at 7T. METHODS: Progressive saturation with adiabatic half
passage excitation was used to determine T1 values of (31) P metabolites in a
group of six healthy volunteers. Saturation-transfer experiments were performed
in seven healthy volunteers by saturating at 0 ppm and 10 ppm with sinc-Gaussian
pulses (90 ms; 10-ms pulse interval; B1 = 17 MUT) prior to excitation.
Localization was performed by surface coils and one-dimensional chemical shift
imaging. Data were analyzed via spectral fitting with the JMRUI software package,
and T1 values were obtained by fitting the data to the signal equation. RESULTS:
The determined longitudinal relaxation time values at 7T were as follows:
phosphoethanolamine, 4.0 +/- 0.2 s; phosphocholine, 1.8 +/- 0.2 s; inorganic
phosphate, 6.1 +/- 0.1 s; phosphodiesters, glycerophosphatidylethanolamine plus
glycerophosphocholine, 2.1 +/- 0.1, and glycerophosphatidylethanolamine, 1.5 +/-
0.1s; gamma-ATP, 2.1 +/- 0.1 s; and alpha-ATP, 2.0 +/- 0.1 s. Saturation-transfer
measurements with saturation pulses at 0 ppm showed a significant signal
reduction in the phosphodiester 2-3 ppm range, whereas the gamma-ATP signal at
2.5 ppm was not affected significantly. CONCLUSION: Longitudinal relaxation times
of phosphorous metabolites in fibroglandular tissue revealed relatively low T1
values for phosphodiesters. Saturation-transfer measurements showed that the
phosphodiester signals were the only signals that were affected significantly,
possibly indicating the presence of mobile phospholipids. Magn Reson Med 76:402
407, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26418726
TI - Synthesis and controlled growth of osmium nanoparticles by electron irradiation.
AB - We have synthesised osmium nanoparticles of defined size (1.5-50 nm) on a B- and
S-doped turbostratic graphitic structure by electron-beam irradiation of an
organometallic osmium complex encapsulated in self-spreading polymer micelles,
and characterised them by transmission electron microscopy (TEM), high-resolution
TEM (HRTEM), and atomic force microscopy (AFM) on the same grid. Oxidation of the
osmium nanoparticles after exposure to air was detected by X-ray photoelectron
spectroscopy (XPS).
PMID- 26418727
TI - Investigation of the Gas-Phase Photolysis and Temperature-Dependent OH Reaction
Kinetics of 4-Hydroxy-2-butanone.
AB - Hydroxyketones are key secondary reaction products in the atmospheric oxidation
of volatile organic compounds (VOCs). The fate of these oxygenated VOCs is
however poorly understood and scarcely taken into account in atmospheric
chemistry modeling. In this work, a combined investigation of the photolysis and
temperature-dependent OH radical reaction of 4-hydroxy-2-butanone (4H2B) is
presented. The objective was to evaluate the importance of the photolysis process
relative to OH oxidation in the atmospheric degradation of 4H2B. A photolysis
lifetime of about 26 days was estimated with an effective quantum yield of 0.08.
For the first time, the occurrence of a Norrish II mechanism was hypothesized
following the observation of acetone among photolysis products. The OH reaction
rate coefficient follows the Arrhenius trend (280-358 K) and could be modeled
through the following expression: k4H2B(T) = (1.26 +/- 0.40) * 10(-12) * exp((398
+/- 87)/T) in cm(3) molecule(-1) s(-1). An atmospheric lifetime of 2.4 days
regarding the OH + 4H2B reaction was evaluated, indicating that OH oxidation is
by far the major degradation channel. The present work underlines the need for
further studies on the atmospheric fate of oxygenated VOCs.
PMID- 26418728
TI - Sugar recognition and protein-protein interaction of mammalian lectins conferring
diverse functions.
AB - Recent advances in structural analyses of mammalian lectins reveal atomic-level
details of their fine specificities toward diverse endogenous and exogenous
glycans. Local variations on a common scaffold can enable certain lectins to
recognize complex carbohydrate ligands including branched glycans and O
glycosylated peptides. Simultaneous recognition of both glycan and the aglycon
moieties enhances the affinity and specificity of lectins such as CLEC-2 and
PILRalpha. Attention has been paid to the roles of galectin and RegIII family of
proteins in protein-protein interactions involved in critical biological
functions including signal transduction and bactericidal pore formation.
PMID- 26418730
TI - A Clinical Case of an SRY-Positive Intersex/Hermaphrodite Holstein Cattle.
AB - A single-born, 15-month-old Holstein cattle, diagnosed as hermaphrodite, was
investigated for estrous cycle, hormonal profiles, karyotype, presence of SRY, as
well as anatomopathological and histological aspects. Normal continuous estrous
cycles and basal testosterone levels were reported. Necropsy showed the presence
of a female genital tract that mismatched a vulvar opening and a male pelvic
urethra continued within a penis. Moreover, we observed islands of seminiferous
tubules with the presence of germline cells, 2 pampiniform plexi, the corpus
cavernosum, the penile urethra, the corpus spongiosum and the glans. Cytogenetic
analyses of the blood cells showed an XX karyotype, while the molecular analyses
revealed the presence of the SRY gene in several tissues, including blood. This
is the first report in the scientific literature of an SRY-positive hermaphrodite
Holstein cattle with continuous ovarian cycles.
PMID- 26418729
TI - BOLD Response Selective to Flow-Motion in Very Young Infants.
AB - In adults, motion perception is mediated by an extensive network of occipital,
parietal, temporal, and insular cortical areas. Little is known about the neural
substrate of visual motion in infants, although behavioural studies suggest that
motion perception is rudimentary at birth and matures steadily over the first few
years. Here, by measuring Blood Oxygenated Level Dependent (BOLD) responses to
flow versus random-motion stimuli, we demonstrate that the major cortical areas
serving motion processing in adults are operative by 7 wk of age. Resting-state
correlations demonstrate adult-like functional connectivity between the motion
selective associative areas, but not between primary cortex and temporo-occipital
and posterior-insular cortices. Taken together, the results suggest that the
development of motion perception may be limited by slow maturation of the
subcortical input and of the cortico-cortical connections. In addition they
support the existence of independent input to primary (V1) and temporo-occipital
(V5/MT+) cortices very early in life.
PMID- 26418731
TI - Hearing threshold distribution and effect of screening in a population-based
German sample.
AB - OBJECTIVE: To establish the status of hearing in adults in Germany and the
effects of screening for noise, tinnitus, ear diseases, and general health on the
distribution of hearing threshold levels (HTL) DESIGN: A cross-sectional
epidemiological study conducted between 2010 and 2012 in two middle-sized cities.
STUDY SAMPLE: A total of 1903 adults aged 18 to 97 years from a randomized sample
drawn from the local registration offices and stratified for age and gender.
RESULTS: Dispersion and distribution of HTL data observed in the population-based
sample are well in line with international results. However, median HTL tend to
be better than in most recent international studies. Screening for "otological
normality" improves the median HTL overall by 3 dB in males and 1 dB in females.
This effect is strongly age-dependent in males and far less pronounced in
females. While by and large HTL medians of females in the screened sample meet
the values expected by ISO 7029:2000, HTL medians of males in middle and higher
age cohorts are better than expected, especially in the frequencies above 2 kHz.
CONCLUSIONS: This study supports international findings that in males, the age
related decrease in hearing sensitivity at high frequencies is smaller than
described by ISO 7029:2000.
PMID- 26418732
TI - End-Stage Kidney Disease Due to Fibrillary Glomerulonephritis and Immunotactoid
Glomerulopathy - Outcomes in 66 Consecutive ANZDATA Registry Cases.
AB - BACKGROUND: Fibrillary glomerulonephritis (FGN) and immunotactoid glomerulopathy
(IG) are uncommon and characterised by non-amyloid fibrillary glomerular
deposits. The aim of this study was to investigate characteristics and outcomes
of patients undergoing renal replacement therapy (RRT) for end-stage kidney
disease (ESKD) secondary to FGN and IG. METHODS: All ESKD patients who commenced
RRT in Australia and New Zealand 1 January 1990 to 31 December 2010 were
included. Outcomes were assessed by Kaplan-Meier, multivariate logistic
regression analysis and multivariable Cox proportional-hazards survival analysis.
RESULTS: Of 45,216 individuals with ESKD, 55 (0.12%) had FGN and 11 (0.02%) had
IG. The median survival of FGN patients on dialysis (5.63 years, 95% CI 3.31
7.96) was not significantly different from patients with other ESKD causes
(median 4.01 years, 95% CI 4.34-4.47; log-rank 1.32, p = 0.25), but was
significantly longer than that of IG patients (median 2.93 years, 95% CI 0.00
6.17; log-rank 4.8, p = 0.03). Thirteen (24%) FGN patients received 13 renal
allografts, 4 (36%) IG patients received 4 renal-allografts and 11,528 (26%)
other ESKD patients received 12,278 renal-allografts. FGN patients experienced
comparable outcomes to other ESKD patients for both 10-year patient survival (100
vs. 84%, p = 0.93) and renal-allograft survival (67 vs. 76%, p = 0.06). For IG,
the median follow-up was 3.66 years with 75% patient survival and 100% renal
allograft survival. One (8%) FGN patient and 1 (25%) IG patient experienced
recurrent FGN and IG respectively in their allograft. CONCLUSION: Patients with
FGN have comparable dialysis and renal transplant outcomes to patients with other
causes of ESKD. IG patients have inferior survival on dialysis, although renal
transplant outcomes are acceptable. Disease recurrence in renal-allografts was
low for both FGN and IG.
PMID- 26418733
TI - E-Waste and Harm to Vulnerable Populations: A Growing Global Problem.
AB - BACKGROUND: Electronic waste (e-waste) is produced in staggering quantities,
estimated globally to be 41.8 million tonnes in 2014. Informal e-waste recycling
is a source of much-needed income in many low- to middle-income countries.
However, its handling and disposal in underdeveloped countries is often unsafe
and leads to contaminated environments. Rudimentary and uncontrolled processing
methods often result in substantial harmful chemical exposures among vulnerable
populations, including women and children. E-waste hazards have not yet received
the attention they deserve in research and public health agendas. OBJECTIVES: We
provide an overview of the scale and health risks. We review international
efforts concerned with environmental hazards, especially affecting children, as a
preface to presenting next steps in addressing health issues stemming from the
global e-waste problem. DISCUSSION: The e-waste problem has been building for
decades. Increased observation of adverse health effects from e-waste sites calls
for protecting human health and the environment from e-waste contamination. Even
if e-waste exposure intervention and prevention efforts are implemented, legacy
contamination will remain, necessitating increased awareness of e-waste as a
major environmental health threat. CONCLUSION: Global, national, and local levels
efforts must aim to create safe recycling operations that consider broad security
issues for people who rely on e-waste processing for survival. Paramount to these
efforts is reducing pregnant women and children's e-waste exposures to mitigate
harmful health effects. With human environmental health in mind, novel
dismantling methods and remediation technologies and intervention practices are
needed to protect communities. CITATION: Heacock M, Kelly CB, Asante KA, Birnbaum
LS, Bergman AL, Brune MN, Buka I, Carpenter DO, Chen A, Huo X, Kamel M, Landrigan
PJ, Magalini F, Diaz-Barriga F, Neira M, Omar M, Pascale A, Ruchirawat M, Sly L,
Sly PD, Van den Berg M, Suk WA. 2016. E-waste and harm to vulnerable populations:
a growing global problem. Environ Health Perspect 124:550-555;
http://dx.doi.org/10.1289/ehp.1509699.
PMID- 26418734
TI - Di-N-Methylation of Anti-Gram-Positive Aminoglycoside-Derived Membrane Disruptors
Improves Antimicrobial Potency and Broadens Spectrum to Gram-Negative Bacteria.
AB - The effect of di-N-methylation of bacterial membrane disruptors derived from
aminoglycosides (AGs) on antimicrobial activity is reported. Di-N-methylation of
cationic amphiphiles derived from several diversely structured AGs resulted in a
significant increase in hydrophobicity compared to the parent compounds that
improved their interactions with membrane lipids. The modification led to an
enhancement in antibacterial activity and a broader antimicrobial spectrum. While
the parent compounds were either modestly active or inactive against Gram
negative pathogens, the corresponding di-N-methylated compounds were potent
against the tested Gram-negative as well as Gram-positive bacterial strains. The
reported modification offers a robust strategy for the development of broad
spectrum membrane-disrupting antibiotics for topical use.
PMID- 26418735
TI - A recursive vesicle-based model protocell with a primitive model cell cycle.
AB - Self-organized lipid structures (protocells) have been proposed as an
intermediate between nonliving material and cellular life. Synthetic production
of model protocells can demonstrate the potential processes by which living cells
first arose. While we have previously described a giant vesicle (GV)-based model
protocell in which amplification of DNA was linked to self-reproduction, the
ability of a protocell to recursively self-proliferate for multiple generations
has not been demonstrated. Here we show that newborn daughter GVs can be restored
to the status of their parental GVs by pH-induced vesicular fusion of daughter
GVs with conveyer GVs filled with depleted substrates. We describe a primitive
model cell cycle comprising four discrete phases (ingestion, replication,
maturity and division), each of which is selectively activated by a specific
external stimulus. The production of recursive self-proliferating model
protocells represents a step towards eventual production of model protocells that
are able to mimic evolution.
PMID- 26418736
TI - Combined Tin-Containing Fluoride Solution and CO2 Laser Treatment Reduces Enamel
Erosion in vitro.
AB - The aim of this in vitro study was to evaluate the effect of combined CO2 laser
and tin-containing fluoride treatment on the formation and progression of enamel
erosive lesions. Ninety-six human enamel samples were obtained, stored in thymol
solution and, after surface polishing, randomly divided into 6 different surface
treatment groups (n = 16 in each group) as follows: no treatment, control (C);
one CO2 laser irradiation (L1); two CO2 laser irradiations (L2); daily
application of fluoride solution (F); combined daily fluoride solution + one CO2
laser irradiation (L1F), and combined daily fluoride solution + two CO2 laser
irradiations (L2F). Laser irradiation was performed at 0.3 J/cm2 (5 us/226
Hz/10.6 um) on day 1 (L1) and day 6 (L2). The fluoride solution contained AmF/NaF
(500 ppm F), and SnCl2 (800 ppm Sn) at pH 4.5. After surface treatment the
samples were submitted to an erosive cycling over 10 days, including immersion in
citric acid (2 min/0.05 M/pH = 2.3) 6 times daily and storage in remineralization
solution (>=1 h) between erosive attacks. At the end of each cycling day, the
enamel surface loss (micrometers) was measured using a 3D laser profilometer.
Data were statistically analyzed by means of a 2-level mixed effects model and
linear contrasts (alpha = 0.05). Group F (-3.3 +/- 2.0 um) showed significantly
lower enamel surface loss than groups C (-27.22 +/- 4.1 um), L1 (-18.3 +/- 4.4
um) and L2 (-16.3 +/- 5.3 um) but higher than L1F (-1.0 +/- 4.4 um) and L2F (1.4
+/- 3.2 um, p < 0.05). Under the conditions of this in vitro study, the tin
containing fluoride solution caused 88% reduction of enamel surface loss, while
its combination with CO2 laser irradiation at 0.3 J/cm2 hampered erosive loss
almost completely.
PMID- 26418739
TI - A Novel Iterative CT Reconstruction Approach Based on FBP Algorithm.
AB - The Filtered Back-Projection (FBP) algorithm and its modified versions are the
most important techniques for CT (Computerized tomography) reconstruction,
however, it may produce aliasing degradation in the reconstructed images due to
projection discretization. The general iterative reconstruction (IR) algorithms
suffer from their heavy calculation burden and other drawbacks. In this paper, an
iterative FBP approach is proposed to reduce the aliasing degradation. In the
approach, the image reconstructed by FBP algorithm is treated as the intermediate
image and projected along the original projection directions to produce the
reprojection data. The difference between the original and reprojection data is
filtered by a special digital filter, and then is reconstructed by FBP to produce
a correction term. The correction term is added to the intermediate image to
update it. This procedure can be performed iteratively to improve the
reconstruction performance gradually until certain stopping criterion is
satisfied. Some simulations and tests on real data show the proposed approach is
better than FBP algorithm or some IR algorithms in term of some general image
criteria. The calculation burden is several times that of FBP, which is much less
than that of general IR algorithms and acceptable in the most situations.
Therefore, the proposed algorithm has the potential applications in practical CT
systems.
PMID- 26418738
TI - A Survey of the ATP-Binding Cassette (ABC) Gene Superfamily in the Salmon Louse
(Lepeophtheirus salmonis).
AB - Salmon lice, Lepeophtheirus salmonis (Kroyer, 1837), are fish ectoparasites
causing significant economic damage in the mariculture of Atlantic salmon, Salmo
salar Linnaeus, 1758. The control of L. salmonis at fish farms relies to a large
extent on treatment with anti-parasitic drugs. A problem related to chemical
control is the potential for development of resistance, which in L. salmonis is
documented for a number of drug classes including organophosphates, pyrethroids
and avermectins. The ATP-binding cassette (ABC) gene superfamily is found in all
biota and includes a range of drug efflux transporters that can confer drug
resistance to cancers and pathogens. Furthermore, some ABC transporters are
recognised to be involved in conferral of insecticide resistance. While a number
of studies have investigated ABC transporters in L. salmonis, no systematic
analysis of the ABC gene family exists for this species. This study presents a
genome-wide survey of ABC genes in L. salmonis for which, ABC superfamily members
were identified through homology searching of the L. salmonis genome. In
addition, ABC proteins were identified in a reference transcriptome of the
parasite generated by high-throughput RNA sequencing (RNA-seq) of a multi-stage
RNA library. Searches of both genome and transcriptome allowed the identification
of a total of 33 genes / transcripts coding for ABC proteins, of which 3 were
represented only in the genome and 4 only in the transcriptome. Eighteen
sequences were assigned to ABC subfamilies known to contain drug transporters,
i.e. subfamilies B (4 sequences), C (11) and G (2). The results suggest that the
ABC gene family of L. salmonis possesses fewer members than recorded for other
arthropods. The present survey of the L. salmonis ABC gene superfamily will
provide the basis for further research into potential roles of ABC transporters
in the toxicity of salmon delousing agents and as potential mechanisms of drug
resistance.
PMID- 26418740
TI - Encountering a cartwheeling princess: relational psychoanalytic therapy of a
child with attachment difficulties and ADHD.
AB - OBJECTIVE: This study was conducted to demonstrate the use and process of
contemporary relational psychoanalytic child therapy to address the interpersonal
implications of attention deficit hyperactivity disorder and interlinked insecure
attachment processes. METHOD: This therapy case study explicates the seven-month
therapeutic process of a seven-year-old girl child highlighting the need for the
child therapist to balance interventions aimed at both the internal and external
world of the child. In essence, this account traces therapeutic scenarios of both
painful and joyful material by means of paying close attention to the entwined
transference and countertransference dynamics as well as creatively and
authentically engaging with the child's way of making sense of self-states,
others and even medication. RESULTS: Key features of this account include the
foundational role of assessment and the compelling mediating role of a puppet as
a co-therapist within the analytic space between psychotherapist and patient.
CONCLUSION: Uniquely, as an inclusive psychoanalytic therapy, relational
psychoanalytic child therapy reconfigures internal object relations of the child
while simultaneously ushering changes into their familial and school context by
utilising the mutuality established between the child and therapist as a central
pivot.
PMID- 26418741
TI - Controlling nonspecific trypsin cleavages in LC-MS/MS-based shotgun proteomics
using optimized experimental conditions.
AB - Trypsin has traditionally been used for enzymatic digestion during sample
preparation in shotgun proteomics. The stringent specificity of trypsin is
essential for accurate protein identification and quantification. But nonspecific
trypsin cleavages are often observed in LC-MS/MS-based shotgun proteomics. To
explore the extent of nonspecific trypsin cleavages, a series of biological
systems including a standard protein mixture, Saccharomyces cerevisiae, human
serum, human cancer cell lines and mouse brain were examined. We found that
nonspecific trypsin cleavages commonly occurred in various trypsin digested
samples with high frequency. To control these nonspecific trypsin cleavages, we
optimized fundamental parameters during sample preparation with mouse brain
homogenates. These parameters included denaturing agents and protein storage
time, trypsin type, enzyme-to-substrate ratio, as well as protein concentration
during digestion. The optimized experimental conditions significantly decreased
the ratio of partially tryptic peptides in total identifications from 28.4% to
2.8%. Furthermore, the optimized digestion protocol was applied to the study of N
glycoproteomics, and the proportions of partially tryptic peptides in enriched
mixtures were also sharply reduced. Our work demonstrates the importance of
controlling nonspecific trypsin cleavages in both shotgun proteomics and
glycoproteomics and provides a better understanding and standardization for
routine proteomics sample treatment.
PMID- 26418737
TI - Evolution of Extensively Drug-Resistant Tuberculosis over Four Decades: Whole
Genome Sequencing and Dating Analysis of Mycobacterium tuberculosis Isolates from
KwaZulu-Natal.
AB - BACKGROUND: The continued advance of antibiotic resistance threatens the
treatment and control of many infectious diseases. This is exemplified by the
largest global outbreak of extensively drug-resistant (XDR) tuberculosis (TB)
identified in Tugela Ferry, KwaZulu-Natal, South Africa, in 2005 that continues
today. It is unclear whether the emergence of XDR-TB in KwaZulu-Natal was due to
recent inadequacies in TB control in conjunction with HIV or other factors.
Understanding the origins of drug resistance in this fatal outbreak of XDR will
inform the control and prevention of drug-resistant TB in other settings. In this
study, we used whole genome sequencing and dating analysis to determine if XDR-TB
had emerged recently or had ancient antecedents. METHODS AND FINDINGS: We
performed whole genome sequencing and drug susceptibility testing on 337 clinical
isolates of Mycobacterium tuberculosis collected in KwaZulu-Natal from 2008 to
2013, in addition to three historical isolates, collected from patients in the
same province and including an isolate from the 2005 Tugela Ferry XDR outbreak, a
multidrug-resistant (MDR) isolate from 1994, and a pansusceptible isolate from
1995. We utilized an array of whole genome comparative techniques to assess the
relatedness among strains, to establish the order of acquisition of drug
resistance mutations, including the timing of acquisitions leading to XDR-TB in
the LAM4 spoligotype, and to calculate the number of independent evolutionary
emergences of MDR and XDR. Our sequencing and analysis revealed a 50-member clone
of XDR M. tuberculosis that was highly related to the Tugela Ferry XDR outbreak
strain. We estimated that mutations conferring isoniazid and streptomycin
resistance in this clone were acquired 50 y prior to the Tugela Ferry outbreak
(katG S315T [isoniazid]; gidB 130 bp deletion [streptomycin]; 1957 [95% highest
posterior density (HPD): 1937-1971]), with the subsequent emergence of MDR and
XDR occurring 20 y (rpoB L452P [rifampicin]; pncA 1 bp insertion [pyrazinamide];
1984 [95% HPD: 1974-1992]) and 10 y (rpoB D435G [rifampicin]; rrs 1400
[kanamycin]; gyrA A90V [ofloxacin]; 1995 [95% HPD: 1988-1999]) prior to the
outbreak, respectively. We observed frequent de novo evolution of MDR and XDR,
with 56 and nine independent evolutionary events, respectively. Isoniazid
resistance evolved before rifampicin resistance 46 times, whereas rifampicin
resistance evolved prior to isoniazid only twice. We identified additional
putative compensatory mutations to rifampicin in this dataset. One major
limitation of this study is that the conclusions with respect to ordering and
timing of acquisition of mutations may not represent universal patterns of drug
resistance emergence in other areas of the globe. CONCLUSIONS: In the first whole
genome-based analysis of the emergence of drug resistance among clinical isolates
of M. tuberculosis, we show that the ancestral precursor of the LAM4 XDR outbreak
strain in Tugela Ferry gained mutations to first-line drugs at the beginning of
the antibiotic era. Subsequent accumulation of stepwise resistance mutations,
occurring over decades and prior to the explosion of HIV in this region, yielded
MDR and XDR, permitting the emergence of compensatory mutations. Our results
suggest that drug-resistant strains circulating today reflect not only
vulnerabilities of current TB control efforts but also those that date back 50 y.
In drug-resistant TB, isoniazid resistance was overwhelmingly the initial
resistance mutation to be acquired, which would not be detected by current rapid
molecular diagnostics employed in South Africa that assess only rifampicin
resistance.
PMID- 26418742
TI - Loss of Endometrial Plasticity in Recurrent Pregnancy Loss.
AB - Menstruation drives cyclic activation of endometrial progenitor cells, tissue
regeneration, and maturation of stromal cells, which differentiate into
specialized decidual cells prior to and during pregnancy. Aberrant responsiveness
of human endometrial stromal cells (HESCs) to deciduogenic cues is strongly
associated with recurrent pregnancy loss (RPL), suggesting a defect in cellular
maturation. MeDIP-seq analysis of HESCs did not reveal gross perturbations in CpG
methylation in RPL cultures, although quantitative differences were observed in
or near genes that are frequently deregulated in vivo. However, RPL was
associated with a marked reduction in methylation of defined CA-rich motifs
located throughout the genome but enriched near telomeres. Non-CpG methylation is
a hallmark of cellular multipotency. Congruently, we demonstrate that RPL is
associated with a deficiency in endometrial clonogenic cell populations. Loss of
epigenetic stemness features also correlated with intragenic CpG hypomethylation
and reduced expression of HMGB2, coding high mobility group protein 2. We show
that knockdown of this sequence-independent chromatin protein in HESCs promotes
senescence and impairs decidualization, exemplified by blunted time-dependent
secretome changes. Our findings indicate that stem cell deficiency and
accelerated stromal senescence limit the differentiation capacity of the
endometrium and predispose for pregnancy failure.
PMID- 26418743
TI - Determining composition of micron-scale protein deposits in neurodegenerative
disease by spatially targeted optical microproteomics.
AB - Spatially targeted optical microproteomics (STOMP) is a novel proteomics
technique for interrogating micron-scale regions of interest (ROIs) in mammalian
tissue, with no requirement for genetic manipulation. Methanol or formalin-fixed
specimens are stained with fluorescent dyes or antibodies to visualize ROIs, then
soaked in solutions containing the photo-tag: 4-benzoylbenzyl-glycyl
hexahistidine. Confocal imaging along with two photon excitation are used to
covalently couple photo-tags to all proteins within each ROI, to a resolution of
0.67 um in the xy-plane and 1.48 um axially. After tissue solubilization, photo
tagged proteins are isolated and identified by mass spectrometry. As a test case,
we examined amyloid plaques in an Alzheimer's disease (AD) mouse model and a post
mortem AD case, confirming known plaque constituents and discovering new ones.
STOMP can be applied to various biological samples including cell lines, primary
cell cultures, ex vivo specimens, biopsy samples, and fixed post-mortem tissue.
PMID- 26418744
TI - Extrinsic and intrinsic signals converge on the Runx1/CBFbeta transcription
factor for nonpeptidergic nociceptor maturation.
AB - The generation of diverse neuronal subtypes involves specification of neural
progenitors and, subsequently, postmitotic neuronal differentiation, a relatively
poorly understood process. Here, we describe a mechanism whereby the neurotrophic
factor NGF and the transcription factor Runx1 coordinate postmitotic
differentiation of nonpeptidergic nociceptors, a major nociceptor subtype. We
show that the integrity of a Runx1/CBFbeta holocomplex is crucial for NGF
dependent nonpeptidergic nociceptor maturation. NGF signals through the ERK/MAPK
pathway to promote expression of Cbfb but not Runx1 prior to maturation of
nonpeptidergic nociceptors. In contrast, transcriptional initiation of Runx1 in
nonpeptidergic nociceptor precursors is dependent on the homeodomain
transcription factor Islet1, which is largely dispensable for Cbfb expression.
Thus, an NGF/TrkA-MAPK-CBFbeta pathway converges with Islet1-Runx1 signaling to
promote Runx1/CBFbeta holocomplex formation and nonpeptidergic nociceptor
maturation. Convergence of extrinsic and intrinsic signals to control
heterodimeric transcription factor complex formation provides a robust mechanism
for postmitotic neuronal subtype specification.
PMID- 26418745
TI - FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase.
AB - Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a
range of human cancers, including non-small cell lung cancer and neuroblastoma
(Hallberg and Palmer, 2013). Vertebrate ALK has been considered to be an orphan
receptor and the identity of the ALK ligand(s) is a critical issue. Here we show
that FAM150A and FAM150B are potent ligands for human ALK that bind to the
extracellular domain of ALK and in addition to activation of wild-type ALK are
able to drive 'superactivation' of activated ALK mutants from neuroblastoma. In
conclusion, our data show that ALK is robustly activated by the FAM150A/B ligands
and provide an opportunity to develop ALK-targeted therapies in situations where
ALK is overexpressed/activated or mutated in the context of the full length
receptor.
PMID- 26418747
TI - Manganese(I)-Catalyzed C-H Aminocarbonylation of Heteroarenes.
AB - A versatile manganese(I) catalyst was employed in C-H aminocarbonylation
reactions of heteroarenes with aryl as well as with alkyl isocyanates using a
removable directing group approach. Detailed experimental mechanistic studies
were suggestive of an organometallic C-H manganesation step, followed by a rate
determining migratory insertion.
PMID- 26418746
TI - Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal
activity of Perforin-2.
AB - Perforin-2 (MPEG1) is an effector of the innate immune system that limits the
proliferation and spread of medically relevant Gram-negative, -positive, and acid
fast bacteria. We show here that a cullin-RING E3 ubiquitin ligase (CRL) complex
containing cullin-1 and betaTrCP monoubiquitylates Perforin-2 in response to
pathogen associated molecular patterns such as LPS. Ubiquitylation triggers a
rapid redistribution of Perforin-2 and is essential for its bactericidal
activity. Enteric pathogens such as Yersinia pseudotuberculosis and
enteropathogenic Escherichia coli disarm host cells by injecting cell cycle
inhibiting factors (Cifs) into mammalian cells to deamidate the ubiquitin-like
protein NEDD8. Because CRL activity is dependent upon NEDD8, Cif blocks ubiquitin
dependent trafficking of Perforin-2 and thus, its bactericidal activity.
Collectively, these studies further underscore the biological significance of
Perforin-2 and elucidate critical molecular events that culminate in Perforin-2
dependent killing of both intracellular and extracellular, cell-adherent
bacteria.
PMID- 26418748
TI - Changes in the gene expression of co-cultured human fibroblast cells and
osteosarcoma cells: the role of microenvironment.
AB - BACKGROUND: The progression of malignant tumors does not depend exclusively on
the autonomous properties of cancer cells; it is also influenced by tumor stroma
reactivity and is under strict microenvironmental control. By themselves, stromal
cells are not malignant, and they maintain normal tissue structure and function.
However, through intercellular interactions or by paracrine secretions from
cancer cells, normal stromal cells acquire abnormal phenotypes that sustain
cancer cell growth and tumor progression. In their dysfunctional state,
fibroblast and immune cells produce chemokines and growth factors that stimulate
cancer cell growth and invasion. In our previous work, we established an in vitro
model based on a monolayer co-culture system of healthy human fibroblasts (HFs)
and human osteosarcoma cells (the MG-63 cell line) that simulates the
microenvironment of tumor cells and healthy cells. The coexistence between MG-63
cells and HFs allowed us to identify the YKL-40 protein as the main marker for
verifying the influence of tumor cells grown in contact with healthy cells.
METHODS: In this study, we evaluated the interactions of HFs and MG-63 cells in a
transwell co-culture system over 24 h, 48 h, 72 h, and 96 h. We analyzed the
contributions of these populations to the tumor microenvironment during cancer
progression, as measured by multiple markers. We examined the effect of siRNA
knockdown of YKL-40 by tracking the subsequent changes in gene expression within
the co-culture. We validated the expression of several genes, focusing on those
involved in cancer cell invasion, inflammatory responses, and angiogenesis: TNF
alpha, IL-6, MMP-1, MMP-9, and VEGF. We compared the results to those from a
transwell co-culture without the YKL-40 knockdown. RESULTS: In a pro-inflammatory
environment promoted by TNF alpha and IL-6, siRNA knockdown of YKL-40 caused a
down-regulation of VEGF and MMP-1 expression in HFs. CONCLUSIONS: These findings
demonstrated that the tumor microenvironment has an influence on the gene
expression of healthy surrounding tissues and on the process of tumorigenicity
and it is emerging as attractive targets for therapeutic strategies.
PMID- 26418749
TI - Flcn-deficient renal cells are tumorigenic and sensitive to mTOR suppression.
AB - Deficiency of tumor suppressor FLCN leads to the activation of the mTOR signaling
pathway in human BHD-associated renal cell carcinomas (RCC). We have previously
developed a renal distal tubule-collecting duct-Henle's loop-specific Flcn
knockout (KO) mouse model (Flcnflox/flox/Ksp-Cre). This mouse model can only
survive for three weeks after birth due to the development of polycystic kidney
and uremia. Whether these cystic solid hyperplasia changes seen in those KO mice
are tumorigenic or malignant is unknown. In this study, we demonstrated that
genetic disruption of Flcn in mouse kidney distal tubule cells could lead to
tumorigenic transformation of these cells to develop allograft tumors with an
aggressive histologic phenotype. Consistent with previous reports, we showed that
the mTOR pathway plays an important role in the growth of these Flcn-deficient
allograft and human UOK 257-1 xenograft tumors. We further demonstrated that the
mTOR inhibitor, sirolimus, suppresses the tumor's growth, suggesting that mTOR
inhibitors might be effective in control of FLCN-deficient RCC, especially in BHD
renal tumorigenesis.
PMID- 26418752
TI - Colonoscopic reduction of colo-colic intussusception in an adult with
immunoglobulin A vasculitis (Henoch-Schonlein purpura).
PMID- 26418751
TI - A strategy to combine pathway-targeted low toxicity drugs in ovarian cancer.
AB - Serous Ovarian Cancers (SOC) are frequently resistant to programmed cell death.
However, here we describe that these programmed death-resistant cells are
nonetheless sensitive to agents that modulate autophagy. Cytotoxicity is not
dependent upon apoptosis, necroptosis, or autophagy resolution. A screen of NCBI
yielded more than one dozen FDA-approved agents displaying perturbed autophagy in
ovarian cancer. The effects were maximized via combinatorial use of the agents
that impinged upon distinct points of autophagy regulation. Autophagosome
formation correlated with efficacy in vitro and the most cytotoxic two agents
gave similar effects to a pentadrug combination that impinged upon five distinct
modulators of autophagy. However, in a complex in vivo SOC system, the pentadrug
combination outperformed the best two, leaving trace or no disease and with no
evidence of systemic toxicity. Targeting the autophagy pathway in a multi-modal
fashion might therefore offer a clinical option for treating recalcitrant SOC.
PMID- 26418754
TI - Synthesis and Properties of C(2h)-Symmetric BN-Heteroacenes Tailored through
Aromatic Central Cores.
AB - The 2-fold successive electrophilic borylation on one aromatic central core led
to a series of C(2h)-symmetric BN-heteroacenes in excellent yields. For the first
time, we introduced trimethylsilyl (TMS) as either leaving group or oriented
group for efficiently improving the preparation of BN-embedded polycyclic
aromatic hydrocarbons (PAHs). The physical properties of the as-synthesized BN
heteroacenes in either solid state or solution can be finely tuned through the
position isomerization or the fused ring numbers of the aromatic central core.
PMID- 26418753
TI - Biocompatibility of common polyimides with human endothelial cells for a
cardiovascular microsensor.
AB - The cardiovasculature is an emerging niche for polyimide microdevices, yet the
biocompatibility of polyimides with human endothelial cells has not been reported
in the literature. In this study, we have evaluated an experimental polyimide
based pressure sensor for biological safety to determine its suitability for
intravascular operation by using an in vitro model of human endothelium,
following ISO 10993-5 protocols for extract tests and direct contact tests.
First, SV-HCEC cells were incubated with extracts derived from common
microfabrication polyimides utilized in the transducer (PMDA-ODA, BPDA-PPD, and a
proprietary thermoplastic adhesive), and then labeled with selective probes to
evaluate the effect of the polyimides on mitochondria and cell viability. Flow
cytometry analysis showed that incubation of SV-HCECs with polyimide extracts
resulted in no significant change in mitochondrial membrane potential (detected
by JC-1) or apoptotic (annexin V) and necrotic (propidium iodide) cell death,
when compared to incubation with extracts of high-density polyethylene (HDPE) and
untreated cells used as negative controls. Second, primary human endothelial
cells were incubated in direct contact with the completed sensor and then labeled
with selective probes for live-dead analysis (calcein-AM, ethidium homodimer-1).
Endothelial cells showed no loss of viability when compared to negative controls.
Combined, the studies show no significant change in early markers of stress or
more strict markers of viability in endothelial cells treated with the polyimides
tested. We conclude that these common microfabrication polyimides and the derived
sensor are not cytotoxic to human endothelial cells, the primary cell type that
cardiovascular sensors will contact in vivo.
PMID- 26418750
TI - Colorectal cancer-related mutant KRAS alleles function as positive regulators of
autophagy.
AB - The recent interest to modulate autophagy in cancer therapy has been hampered by
the dual roles of this conserved catabolic process in cancer, highlighting the
need for tailored approaches. Since RAS isoforms have been implicated in
autophagy regulation and mutation of the KRAS oncogene is highly frequent in
colorectal cancer (CRC), we questioned whether/how mutant KRAS alleles regulate
autophagy in CRC and its implications. We established two original models, KRAS
humanized yeast and KRAS-non-cancer colon cells and showed that expression of
mutated KRAS up-regulates starvation-induced autophagy in both. Accordingly, KRAS
down-regulation inhibited autophagy in CRC-derived cells harboring KRAS
mutations. We further show that KRAS-induced autophagy proceeds via up-regulation
of the MEK/ERK pathway in both colon models and that KRAS and autophagy
contribute to CRC cell survival during starvation. Since KRAS inhibitors have
proven difficult to develop, our results suggest using autophagy inhibitors as a
combined/alternative therapeutic approach in CRCs with mutant KRAS.
PMID- 26418755
TI - Decarboxylative Alkylcarboxylation of alpha,beta-Unsaturated Acids Enabled by
Copper-Catalyzed Oxidative Coupling.
AB - A facile and general method for copper-catalyzed decarboxylative
alkylcarboxylation of cinnamic acids with dimethyl 2,2'-azobis(2
methylpropionate) has been developed. The scope and versatility of the reaction
was demonstrated, and a broad range of substrates bearing electron-donating and
withdrawing groups on the aromatic rings were all compatible with this reaction
to provide desired beta,gamma-unsaturated esters in moderate to good yields.
Moreover, alpha,beta-unsaturated acids with a carbonyl group on the gamma
position of acrylic acids also smoothly proceeded to furnish the desired products
in good yields.
PMID- 26418756
TI - GNPAT variant is not associated with severe iron overload in Irish C282Y
homozygotes.
PMID- 26418758
TI - MicroRNAs as regulators of beta-cell function and dysfunction.
AB - In the last decade, there has been an explosion in both the number of and
knowledge about miRNAs associated with both type 1 and type 2 diabetes. Even
though we are presently in the initial stages of understanding how this novel
class of posttranscriptional regulators are involved in diabetes, recent studies
have demonstrated that miRNAs are important regulators of the islet
transcriptome, controlling apoptosis, differentiation and proliferation, as well
as regulating unique islet and beta-cell functions and pathways such as insulin
expression, processing and secretion. Furthermore, a large number of miRNAs have
been linked to diabetogenic processes induced by elevated levels of glucose, free
fatty acids and inflammatory cytokines. Thus, miRNAs are novel therapeutic
targets with the potential of protecting the beta-cell, and there is proof of
principle that miRNA antagonists, so-called antagomirs, are effective in vivo for
other disorders. miRNAs are exported out of cells in exosomes, raising the
intriguing possibility of cell-to-cell communication between distant tissues via
miRNAs and that miRNAs can be used as biomarkers of beta-cell function, mass and
survival. The purpose of this review is to provide a status on how miRNAs control
beta-cell function and viability in health and disease.
PMID- 26418759
TI - Thrombotic thrombocytopenic purpura: from diagnosis to therapy.
AB - PURPOSE OF REVIEW: Thrombotic thrombocytopenic purpura (TTP) is a rare but
challenging disease for intensive care specialists. Patients with acute TTP
frequently require admission to the intensive care unit because of organ
dysfunctions due to the disease or because of the risk of sudden aggravation at
the onset of the disease. This review aims at describing recent evolutions in the
diagnosis and for the management of TTP for the use of intensive care
specialists. RECENT FINDINGS: The use of A Disintegrin and Metalloprotease with
ThromboSpondin type 1 repeats (ADAMTS13) activity along with clinico-biological
features to define TTP by most researchers' teams has led to easier
interpretation of the literature. The main issues in TTP treatment in 2015 remain
the indication and timing of introduction of anti-CD20 antibody rituximab for the
treatment of inaugural TTP and the preemptive use of rituximab in asymptomatic
patients with decreasing ADAMTS13 activity. SUMMARY: The classification of
thrombotic microangiopathies has evolved from a clinical to a pathophysiological
definition. TTP is characterized by a severe ADAMTS13 deficiency that can be
documented in vitro, along with anti-ADAMTS13 antibodies in most adult cases.
Plasmapheresis and immunosuppressive therapy with steroids remain the standard of
care for acute inaugural TTP. Anti-CD20 monoclonal antibody rituximab is safe and
indicated in relapsing and/or refractory TTP. Its indication in inaugural TTP
remains to be evaluated but is nevertheless recommended by experts. Novel
therapies for TTP are still in preclinical phases.
PMID- 26418757
TI - Association Between Atrial Fibrillation and Costs After Myocardial Infarction: A
Community Study.
AB - BACKGROUND: The authors sought to estimate incremental economic impact of atrial
fibrillation (AF) and the timing of its onset in myocardial infarction (MI)
patients. HYPOTHESIS: Concurrent AF and its timing are associated with higher
costs in MI patients. METHODS: This retrospective cohort study included incident
MI patients from Olmsted County, Minnesota, treated between November 1, 2002, and
December 31, 2010. We compared inflation-adjusted standardized costs accumulated
between incident MI and end of follow-up among 3 groups by AF status and timing:
no AF, new-onset AF (within 30 days after index MI), and prior AF. Multivariate
adjustment of median costs accounted for right-censoring in costs. RESULTS: The
final study cohort had 1389 patients, with 989 in no AF, 163 in new-onset AF, and
237 in prior AF categories. Median follow-up times were 3.98, 3.23, and 2.55
years, respectively. Mean age at index was 67 years, with significantly younger
patients in the no AF group (64 years vs 76 and 77 years, respectively; P <
0.001). New-onset and prior AF patients had more comorbid conditions
(hypertension, heart failure, and chronic obstructive pulmonary disease). After
accounting for differences in baseline characteristics, we found adjusted median
(95% confidence interval) costs of $73 000 ($69 000-$76 000) for no AF; $85 000
($81 000-$89 000) for new-onset AF; and $97 000 ($94 000-$100 000) for prior AF.
Inpatient costs composed the largest share of total median costs (no AF, 82%; new
onset AF, 84%; prior AF, 83%). CONCLUSIONS: Atrial fibrillation frequently
coexists with MI and imposes incremental costs, mainly attributable to inpatient
care. Timing of AF matters, as prior AF was found to be associated with higher
costs than new-onset AF.
PMID- 26418761
TI - Pediatric blunt abdominal trauma: current management.
AB - PURPOSE OF REVIEW: Nonoperative management of pediatric blunt abdominal injury
has changed significantly in the last few years. RECENT FINDINGS: Improved
resource utilization in the diagnosis of pediatric abdominal injury has been
described. Hemodynamic status, rather than grade of injury, now guides care.
Stable patients spend less time in the hospital, return to school upon discharge,
and are allowed lower hemoglobin levels prior to transfusion. ICUs are reserved
for those with recent or ongoing bleeding, previously unstable patients, or
children with concomitant injuries necessitating ICU. Risk factors for failure
and evidence for adjuncts to nonoperative management are emerging. Operative
management of certain pancreatic injuries may have more favorable outcomes than
nonoperative management. SUMMARY: Sufficient evidence has become available to
radically change the management of pediatric abdominal injury, which is being
incorporated into new evidence-based management algorithms.
PMID- 26418760
TI - Endpoints in resuscitation.
AB - PURPOSE OF REVIEW: Shock occurs because of a failure to deliver adequate oxygen
to meet the metabolic demands of the body resulting in metabolic acidosis,
inflammation, and coagulopathy. Resuscitation is the process of treating shock in
an attempt to restore normal physiology. Various hemodynamic, metabolic, and
regional endpoints have been described to evaluate the degree of shock and guide
resuscitation efforts. We will briefly describe these endpoints, and propose
damage control resuscitation as an additional endpoint. RECENT FINDINGS: Serum
lactate, base deficit, and pH are well established endpoints of resuscitation
that provide valuable information when trended over time; however, a single value
is inadequate to determine adequacy of resuscitation. Rapid normalization of
central venous oxygen concentration has been associated with improved survival,
and bedside transthoracic echocardiography can be a reliable assessment of volume
status. In hypovolemic/hemorrhagic shock, early hypotensive, or controlled
resuscitation strategies have been associated with improved survival, and
hemostatic strategies guided by thrombelastography using a balanced transfusion
approach result in improved hemostasis. SUMMARY: Numerous endpoints are
available; however, no single endpoint is universally applicable. Damage control
resuscitation strategies have demonstrated improved survival, hemostasis, and
less early death from exsanguination, suggesting that hemorrhage control should
be an additional endpoint in resuscitation.
PMID- 26418763
TI - MetaPhlAn2 for enhanced metagenomic taxonomic profiling.
PMID- 26418762
TI - Widespread nuclease contamination in commonly used oxygen-scavenging systems.
PMID- 26418764
TI - What if stem cells turn into embryos in a dish?
AB - Recent studies show that pluripotent stem cells can undergo self-organized
development in vitro into structures that mimic the body plan of the post
implantation embryo. Modeling human embryogenesis in a dish opens up new
possibilities for the study of early development and developmental disorders, but
it may also raise substantial ethical concerns.
PMID- 26418766
TI - Diving deeper to predict noncoding sequence function.
PMID- 26418765
TI - Voltage sensors: challenging, but with potential.
PMID- 26418767
TI - Photochemical Hydrogen Doping Induced Embedded Two-Dimensional Metallic Channel
Formation in InGaZnO at Room Temperature.
AB - The photochemical tunability of the charge-transport mechanism in metal-oxide
semiconductors is of great interest since it may offer a facile but effective
semiconductor-to-metal transition, which results from photochemically modified
electronic structures for various oxide-based device applications. This might
provide a feasible hydrogen (H)-radical doping to realize the effectively H-doped
metal oxides, which has not been achieved by thermal and ion-implantation
technique in a reliable and controllable way. In this study, we report a
photochemical conversion of InGaZnO (IGZO) semiconductor to a transparent
conductor via hydrogen doping to the local nanocrystallites formed at the
IGZO/glass interface at room temperature. In contrast to thermal or ionic
hydrogen doping, ultraviolet exposure of the IGZO surface promotes a
photochemical reaction with H radical incorporation to surface metal-OH layer
formation and bulk H-doping which acts as a tunable and stable highly doped n
type doping channel and turns IGZO to a transparent conductor. This results in
the total conversion of carrier conduction property to the level of metallic
conduction with sheet resistance of ~16 Omega/?, room temperature Hall mobility
of 11.8 cm(2) V(-1) sec(-1), the carrier concentration at ~10(20) cm(-3) without
any loss of optical transparency. We demonstrated successful applications of
photochemically highly n-doped metal oxide via optical dose control to
transparent conductor with excellent chemical and optical doping stability.
PMID- 26418768
TI - Superthin Abdominal Wall Glove-Like Flap Combined With Vacuum-Assisted Closure
Therapy for Soft Tissue Reconstruction in Severely Burned Hands or With
Infection.
AB - Severe burn and infection to hands always involves the deep structures, such as
tendons, joints, and bones. These wounds cannot be closed immediately and
therefore creates a high risk for complication. We presented 9 cases with deep
dermal burns to the dorsal of the hand (6 electrical burns and 3 thermal crush
injuries) with wound infections in 2 cases. The vacuum-assisted closure system
was used continuously until the flap reconstruction was performed. A random
pattern and superthin abdominal wall skin flap-like glove was designed. The flap
was transferred to the defected portion of the dorsum of the hand and resected
from the abdominal wall about 3 weeks later. The flaps in 8 of the patients
treated by this technique survived completely and partial necrosis of the distal
flap occurred in 1 patient. The defect resolved after operative treatment and the
function of the hands and fingers were successfully salvaged. All patients
resulted in having a satisfactory aesthetic outcome with no or minor discomfort
at the abdominal donor area. Integration of the vacuum-assisted closure system
and the superthin abdominal wall glove-like flap reconstruction appeared to be
successful and should be considered in patients with severely burned hands.
PMID- 26418770
TI - A New Method to Control Tendon Tension in the Transfer of Extensor Indicis
Proprius to Extensor Pollicis Longus Rupture.
AB - This study evaluated the outcomes of extensor indicis proprius (EIP) transfer
based on varying degrees of thumb extension after EIP transfer and elongation of
the EIP. A total of 24 cases with extensor pollicis longus (EPL) ruptures who
underwent EIP to EPL transfer were analyzed prospectively. The EIP transfer was
performed with neutral wrist positioning. In group I (12 cases), EIP and EPL were
sutured on the thumb in neutral state at interphalangeal joint, and the mean EIP
elongation of this group measured 0.2 cm (range, -0.5 to 0.5 cm). In group II (12
cases), EIP and EPL were sutured on the thumb in full extension state at
interphalangeal joint, and the mean EIP elongation measured 0.7 cm (range, 0.5
1.5 cm). The mean follow-up period was 13.5 months. The 2 groups were compared
based on thumb motion, grip strength, pinch power, and the Disabilities of the
Arm, Shoulder, and Hand questionnaire score. Extension of the thumb at the
interphalangeal joint was -5.2 degrees in group I and 7.2 degrees in group II,
demonstrating statistically significant differences. No significant differences
were found between the 2 groups in other parameters. In EIP transfer, thumb in
extension after transfer and EIP elongation is recommended for restoring thumb
extension at the interphalangeal joint.
PMID- 26418769
TI - Flexor Tenosynovitis Due to Tuberculosis in Hand and Wrist: Is Tenosynovectomy
Imperative?
AB - The treatment of flexor tenosynovitis in the hand and wrist due to tuberculosis
is controversial. Although some authors recommend the antituberculous
chemotherapy, the others recommend the surgical treatment. In this article, 12
patients with synovial tuberculosis of the flexor aspect of the hand and the
wrist were evaluated with respect to diagnosis and treatment modalities. None of
the patients had a history of tuberculosis, concomitant disease,
immunosuppressive drug use, drug abuse, and human immunodefficiency virus
positivity. A chest x-ray and family screening were performed in all of the
cases, none had evidence of tuberculosis in the lung. The biopsy,
histopathological examination, acid-fast bacillus staining, and BACTEC
tuberculosis culture were performed. Antituberculous chemotherapy was initiated
in patients diagnosed with tuberculosis by either histological or microbiological
examinations. The patients did not undergo any further surgery after biopsy
procedures. The lesions regressed totally in all patients after 3 months of
treatment. Carpal tunnel syndrome symptoms and signs recruited at five months of
treatment. In patients with flexor tuberculosis tenosynovitis, it is possible to
achieve good results by applying only medical therapy after a biopsy, and without
the need for further surgery.
PMID- 26418771
TI - Operative Treatment of Lymphedema Using Suction-Assisted Lipectomy.
AB - BACKGROUND: Surgical management of lymphedema includes removal of affected
tissues (excisional procedures), or operations that create new lymphatic
connections (physiologic procedures). The purpose of this study was to determine
the efficacy of one type of excisional procedure, suction-assisted lipectomy, for
extremity lymphedema. METHODS: Patients treated in our Lymphedema Program between
2007 and 2015 with liposuction that had postoperative follow-up were reviewed.
The diagnosis of lymphedema was made by history/physical examination and
confirmed with lymphoscintigraphy. Patient sex, age, type of lymphedema (primary
or secondary), location of disease, infection history, volume of lipoaspirate,
and reduction of extremity volume were recorded. RESULTS: Fifteen patients were
included, mean age was 45 years (range, 17-71). Six patients had secondary upper
extremity lymphedema, and 9 patients had lower limb disease. Eight patients had a
history of repeated cellulitis involving the lymphedematous extremity. Mean
lipoaspirate volume was 1612 mL (range, 1200-2800) for the upper extremity and
2902 mL (range, 2000-4800) for the lower limb. Postoperative follow-up averaged
3.1 years. The mean reduction in excess extremity volume was 73% (range, 48% to
94%), and patients reported improvement in their quality of life. CONCLUSIONS:
Suction-assisted lipectomy is an effective technique to reduce extremity volume
for patients with lymphedema.
PMID- 26418772
TI - Indocyanine Green Lymphographic Signs of Lymphatic Collateral Formation in Lower
Extremity Lymphedema After Cancer Resection.
AB - Indocyanine green lymphography has recently been used to assess lymphatic vessel
function in lymphedema patients. Postoperative collateral lymphatic vessels
toward ipsilateral axillary lymph nodes are rarely seen above the umbilical level
in lower lymphedema patients. Between January 2012 and December 2014, we
performed indocyanine green lymphography of 192 limbs in 96 lower extremity
lymphedema cases. As a result, dermal back flow appeared in 95 cases, with 38 in
the lower abdominal area and 31 in the genital area. We confirmed 3 cases of
superficial lymphatic collateral ways extending above the umbilical level to the
axillary lymph nodes. All 3 cases had similarity in lower abdominal edema, so
excessive lymphatic fluid in the lower abdomen was assumed to be the cause.
Lymphatic collateral ways from abdomen to axillary lymph nodes in this study was
likely to be designed to prevent the progress of lymphedema.
PMID- 26418773
TI - An Application of Keystone Perforator Island Flap for Closure of Lumbosacral
Myelomeningocele Defects.
AB - Myelomeningocele, also known as spina bifida, is the commonest form of neural
tube defect in which both meninges and spinal cord herniate through a large
vertebral defect. It may be located at any spinal level; however; lumbosacral
involvement is most common. After birth, the closure of spinal lesion is
preferably undertaken in the first 48 hours to minimize the risk of injury and
central nervous system infection. Relatively small skin defects overlying the
dural repair may be directly closed. However, larger defects require
reconstructive closure. Numerous methods of reconstruction have been described,
such as split skin graft, local flaps or lumbosacral fasciocutaneous flaps,
muscle flaps using latissimus dorsi, gluteal or paraspinous muscles, and
perforator flaps namely superior gluteal artery perforators, and dorsal
intercostal artery perforator flaps. At Monash Health, Victoria, we have used the
keystone perforator island flaps to reconstruct lumbosacral myelomeningocele
defects on 5 newborns between January 2008 and January 2014. This article
evaluates the short-term and long-term outcomes of these patients who were
followed up for 10 to 66 months.
PMID- 26418774
TI - Preoperative Imaging for Thoracic Branch of Supraclavicular Artery Flap: A
Comparative Study of Contrast-Enhanced Ultrasound With Three-Dimensional
Reconstruction and Color Duplex Ultrasound.
AB - OBJECTIVE: The thoracic branch of supraclavicular artery (TBSA) flap has been
widely used to reconstruct face and neck defects. However, the branches of the
supraclavicular artery (SCA) exhibit considerable anatomical variations. The aim
of this study was to evaluate and compare the role of contrast-enhanced
ultrasound (CEUS) with 3-dimensional (3D) reconstruction and regular color duplex
ultrasonography (CDUS) in the preoperative assessment of TBSA flap. METHODS: From
May 2009 to October 2013, 20 patients (involving 26 flaps) receiving anterior
chest flaps for lower face and neck reconstruction underwent both CDUS and CEUS
with 3D reconstruction preoperatively for detecting the TBSAs. The number of
TBSAs, their caliber, peak systolic velocity (PSV), and course were recorded. In
case of an absent TBSA, the second and third perforators of the internal mammary
artery were detected. The preoperative imaging data were compared with the
intraoperative findings to evaluate the value of CDUS and CEUS with 3D
reconstruction for planning and performing the TBSA flaps. All patients were
followed up for more than 1 year. RESULTS: A total of 37 TBSAs in 16 flaps were
found by CDUS with a mean caliber of 0.6 +/- 0.1 mm and a mean PSV of 13.1 +/-
1.6 cm/s, whereas 48 TBSAs in 20 flaps were found by CEUS with a mean caliber of
0.8 +/- 0.2 mm and a mean PSV of 12.5 +/- 2.1 cm/sec. In 18 flaps with TBSA PSV
above 10 cm/s, pedicled TBSA flaps were performed, whereas pedicled or free
internal mammary artery flaps were chosen as alternative for the remaining 8
flaps. All 48 TBSAs were found intraoperatively and their origin from the SCA
confirmed, indicating specificity and positive predictive value of both CDUS and
CEUS were 100% in localizing TBSA preoperatively, whereas sensitivity and
negative predictive value of CEUS were higher than using CDUS. CONCLUSIONS: The
branches of SCA have marked anatomical variations. CEUS with 3D reconstruction
has advantages over CDUS for the preoperative assessment of the donor-site
vascular supply of TBSA flaps.
PMID- 26418775
TI - Reverse-Flow Lateral Tarsal Island Flap for Covering the Great Toe Donor Site of
Wraparound Flap.
AB - BACKGROUND: Coverage of the great toe donor site of wraparound flap remains a
challenge. This report presents the results of using an innervated pedicled
reverse-flow lateral tarsal island flap for covering the great toe donor site of
wraparound flap. PATIENTS AND METHODS: Between 2005 and 2010, 11 reverse-flow
lateral tarsal island flaps were used to cover the great toe donor site of
wraparound flap in 11 patients. This pedicled flap designed on the lateral tarsal
area of foot was based distally on the dorsalis pedis artery; the lateral dorsal
pedal cutaneous nerve was incorporated into the reverse-flow lateral tarsal
island flap and coapted with the first plantar digital nerve. The donor sites of
reverse-flow lateral tarsal island flap were covered with inguinal full-thickness
skin grafts. RESULTS: All flaps achieved primary healing except for two that
suffered from mild venous insufficiency which was managed by conservative
intervention. All skin grafts covering the donor site of reverse-flow lateral
tarsal island flap healed uneventfully. The mean follow-up was 24 months (range,
18-48 months). The mean hallux metatarsophalangeal-interphalangeal scale score
was 92 points (range, 85-97 points) at 6 months postoperatively. The static 2
point discrimination of the reverse-flow lateral tarsal island flap ranged from 6
to 14 mm (mean 10 mm). None of the patients were restricted in standing or
walking during follow-up. CONCLUSIONS: The reverse-flow lateral tarsal island
flap based distally on the dorsalis pedis artery has a constant pedicle that is
sufficiently long. This innervated pedicle flap is a reliable option to cover the
great toe donor site of wraparound flap with satisfactory functional and cosmetic
results and acceptable donor site morbidity.
PMID- 26418776
TI - The Pacman Perforator-Based V-Y Advancement Flap for Reconstruction of Pressure
Sores at Different Locations.
AB - BACKGROUND: Many procedures have been proposed for the treatment of pressure
sores, and V-Y advancement flaps are widely used to repair a defect.
Unfortunately, the degree of mobility of a V-Y advancement flap is dependent on
the laxity of the underlying subcutaneous tissue. This is an important
disadvantage of traditional V-Y advancement flap and limits its use.We used V-Y
advancement flaps as perforator-based to overcome mobility restriction problem,
with a further modification (Pacman-like shape) to improve the covering surface
area of the flap. METHODS: Between January 2012 and December 2014, the authors
used 37 V-Y Pacman perforator-based flaps in 33 consecutive patients for coverage
of defects located at sacral (n = 21), ischial (n = 13), trochanter (n = 1)
regions. There were 27 male and 6 female patients with a mean age of 49.9 years
(range, 15-74 years). RESULTS: All flaps survived completely (92.3%) except 3 in
which one of them had undergone total necrosis due to hematoma and the other 2
had partial necrosis. No venous congestion was observed. The mean follow-up
period was 14.9 months (range, 2-38 months). No flap surgery-related mortality or
recurrence of pressure sores was noted. CONCLUSIONS: The V-Y Pacman perforator
based advancement flaps are safe and very effective for reconstruction of
pressure sores at various regions. The advantage of our modification procedure
include shorter operative time, lesser pedicle dissection, low donor site
morbidity, good preservation of muscle, and offers remarkable excursion to the V
Y flap, which make the V-Y Pacman perforator-based flaps an excellent choice for
large pressure sore coverage.
PMID- 26418777
TI - The Versatile Extended Thoracodorsal Artery Perforator Flap for Breast
Reconstruction.
AB - BACKGROUND: The thoracodorsal artery perforator (TAP) flap is a versatile tool
that can be used to reconstruct the breast. The authors use preoperative
perforator mapping using color Doppler ultrasonography and present a safe,
efficient harvesting technique to demonstrate reliable use of the TAP flap in
reconstructive surgery. METHODS: A multicenter, retrospective review was
performed on all patients undergoing TAP flap reconstruction from August 2011 to
November 2014. Data were collected from patient records as well as outpatient
interviews. RESULTS: A total of 106 TAP flaps were performed in 97 patients. The
flaps were raised with either 1 perforator (42/106), 2 perforators (55/106), or
three perforators (9/106), and turned as a propeller in 99 of 106 (93%) flaps or
buried as a turnover in 7 of 106 (7%) of flaps. The mean operative time was 200
minutes (range, 60-485). Major complications occurred in 10 of 106 (10%) cases
and included hematoma (1/108), venous congestion (2/108), and partial flap
necrosis (7/108). The reconstructive goal was achieved in 103 of 106 (97%) flaps.
CONCLUSIONS: The TAP flap is a pedicled, fasciocutaneous flap that can be used
for total breast reconstruction as well as breast conserving surgery. This large,
multicenter series describes our techniques of preoperative perforator mapping
and a fast, reliable harvest. Reconstructive goals are accomplished in the great
majority of patients.
PMID- 26418778
TI - Primary Buttonhole Mastopexy and Nipple-Sparing Mastectomy: A Preliminary Report.
AB - BACKGROUND: Patients undergoing nipple-sparing mastectomy and immediate-implant
based reconstruction occasionally require a mastopexy based on their breast size
and degree of ptosis. Previous reports have shown the feasibility of mastopexy
nipple-sparing mastectomy in selected patients to raise the nipple up to 5 cm.
Major mastopexy with nipple transposition more than 6 cm in conjunction with
nipple-sparing mastectomy for therapeutic indications has not been described. The
authors review their experience with primary buttonhole mastopexy performed in
conjunction with nipple-sparing mastectomy. METHODS: Between 2008 and 2014, 16
patients (32 breasts) underwent bilateral primary mastopexy and nipple-sparing
mastectomy with immediate staged implant-based reconstruction. The Passot
buttonhole technique was used for the mastopexy in all patients, raising the
nipple from 7 to 12 cm. Tumor-related data, risk factors, breast size, degree of
ptosis, expander size, fill volume, selection criteria, and complications are
discussed. RESULTS: The average follow-up period was 33 months (range, 14 to 80
months). There were no tumor recurrences, and all patients completed their
reconstruction. Two patients required removal of the expander and delayed
reconstruction because of infection and implant exposure due to nipple-areola
loss. The reasons for nipple-areola loss and technical modifications to enhance
skin viability by retaining a thin layer of subareolar breast tissue for removal
during the second-stage implant exchange are discussed. CONCLUSIONS: Primary
mastopexy using the buttonhole technique performed together with nipple-sparing
mastectomy is a safe procedure with predictable results in patients with very
large or ptotic breasts requiring lifts greater than 6 cm. The success of the
combined procedure depends on preserving a thin layer of subareolar breast tissue
and removing it at the time of implant exchange.
PMID- 26418779
TI - Getting a Valid Survey Response From 662 Plastic Surgeons in the 21st Century.
AB - INTRODUCTION: Web-based surveys save time and money. As electronic questionnaires
have increased in popularity, telephone and mailed surveys have declined. With
any survey, a response rate of 75% or greater is critical for the validity of any
study. We wanted to determine which survey method achieved the highest response
among academic plastic surgeons. METHODS: All American Association of Plastic
Surgeons members were surveyed regarding authorship issues. They were randomly
assigned to receive the questionnaire through 1 of 4 methods: (A) emailed with a
link to an online survey; (B) regular mail; (C) regular mail + $1 bill, and (D)
regular mail + $5 bill. Two weeks after the initial mailing, the number of
responses was collected, and nonresponders were contacted to remind them to
participate. The study was closed after 10 weeks. Survey costs were calculated
based on the actual cost of sending the initial survey, including stationary,
printing, postage (groups B-D), labor, and cost of any financial incentives. Cost
of reminders to nonresponders was calculated at $5 per reminder, giving a total
survey cost. RESULTS: Of 662 surveys sent, 54 were returned because of incorrect
address/email, retirement, or death. Four hundred seventeen of the remaining 608
surveys were returned and analyzed. The response rate was lowest in the online
group and highest in those mailed with a monetary incentive. CONCLUSIONS: Despite
the convenience and low initial cost of web-based surveys, this generated the
lowest response. We obtained statistically significant response rates (79% and
84%) only by using postal mail with monetary incentives and reminders. The
inclusion of a $1 bill represented the greatest value and cost-effective survey
method, based on cost per response.
PMID- 26418780
TI - Digital Sympathectomy in Patients With Scleroderma: An Overview of the Practice
and Referral Patterns and Perceptions of Rheumatologists.
AB - PURPOSE: Periarterial sympathectomy is a treatment option for patients with
systemic sclerosis (SSc) suffering from digital vasculopathy. Despite potential
benefits of ulcer healing, pain improvement, and amputation prevention, this
operation appears to be infrequently performed. The aims of our study are as
follows: (1) to assess national digital sympathectomy rates in patients with SSc
and (2) to improve our understanding of referring physicians' perceptions of
operative management and access to hand surgeons. Our hypothesis is that
rheumatologists' practices largely influence their referral patterns for digital
sympathectomy. METHODS: To determine the rates and demographics of hospitalized
patients with SSc who had undergone digital sympathectomy, we queried the
Nationwide Inpatient Sample from 2006 to 2010. Additionally, we mailed a self
administered survey to a national sample of 500 board-certified rheumatologists
to elicit their practice patterns and perceptions of digital sympathectomy. Using
logistic regression, we analyzed potential predictor variables associated with
rheumatologists performing the following: (1) routinely counseling patients about
digital sympathectomy and (2) expressing the desire to refer these patients for
operative evaluation. RESULTS: Of 348,539 hospitalizations associated with a
diagnosis of SSc, only 0.2% were for digital sympathectomy. Our questionnaire
revealed that only 50% of rheumatologists routinely counseled, whereas 67%
expressed the desire to refer. Factors associated with increased rheumatologists'
interest in surgical management for patients with SSc included positive
perception of the operation's efficacy, comfort with postoperative management,
and interdisciplinary relationship with a hand surgeon. DISCUSSION: Critical
components to increasing appropriate utilization of digital sympathectomy include
enhancing rheumatologists' understanding of the operation, comfort with
postoperative management, and promoting strong, interdisciplinary relationships
with hand surgeons. Increasing education and awareness, as well as establishing a
solid referral network of hand surgeons may thereby improve patient access to
digital sympathectomy.
PMID- 26418781
TI - Mjolnir.
PMID- 26418782
TI - Pericranial Flap for Inner Lining in Nasal Reconstruction.
AB - INTRODUCTION: The general principle in nasal reconstruction is to reconstruct the
3 layers of skin, cartilage, and mucosa. Reconstructing the inner lining remains
a challenge especially when adjacent tissues are not available after tumor
resection. The galea and pericranial flaps (PFs) are widely used in anterior
skull base reconstructive surgery.We evaluated the use of the PF for the inner
nasal lining in an anatomical cadaver study and present its clinical application
in patients with benign and malignant tumors of the nose and anterior skull base.
METHODS: Four fresh cadavers were injected with red-colored silicone for
determining the pattern of vascularization of supraorbital (SOA) and
supratrochlear (STA) arteries of each PF. Four surgical cases (2 nasocranial
meningiomas, 1 nasal melanoma, and 1 nasal squamous cell carcinoma) received PF
for reconstruction of inner lining. RESULTS: The median distances between the
superior orbital rim and the division of the deep and superficial branches of STA
and SOA were 8 +/- 3.3 mm and 8 +/- 3.7 mm, respectively. The maximum measured
distance was 11 mm. The SOA provided the longest axial vascularization (70.7 +/-
13. 9 mm) compared with STA (35 +/- 10.4 mm). Median length of PF for subtotal
nasal reconstruction including tip and columella were 70 +/- 5 mm and 22.5 +/-
3.5 mm, respectively.Three cases were successfully reconstructed with PF up to
the distal border of the upper lateral cartilage. In 1 patient, distal necrosis
of tip and columella occurred. CONCLUSIONS: The blood supply of the PF is mainly
based on the SOA arteries. Thus, superficial dissection must end 15 mm above the
orbital rim to ensure the survival of the flap. Pericranial flap can be applied
for inner lining in combined nasocranial, septal, and nasal defects with
extension down to the distal border of the upper lateral cartilage.
Vascularization is reliable in flaps up to a length of 70 mm.
PMID- 26418783
TI - Reconstruction of a Large External Hemipelvectomy Defect After Chordoma Resection
Using a 5-Component Chimeric Rotational Flap.
PMID- 26418784
TI - Donor Site Aesthetic Enhancement With Preoperative Botulinum Toxin in Forehead
Flap Nasal Reconstruction.
AB - BACKGROUND: Donor site scarring after forehead flap nasal reconstruction is
acceptable. However, as aesthetic outcomes standards for cosmetic and
reconstructive surgery merge, we aim to enhance results. We recently demonstrated
the cosmetic benefit of botulinum toxin type A (BTX-A) for cleft lip cheiloplasty
outcomes. We hypothesize that similar mechanism(s) benefit forehead flap donor
scars. METHODS: A single surgeon performed 26 forehead flap reconstructions.
Indications were cancer (n = 17), trauma (n = 3), and congenital deformity (n =
6). In this split-scar study half the forehead was pretreated with BTX-A and half
with normal saline after random assignment. Photographs were evaluated at most
recent follow-up. Scar evaluation was based on photographs by 3 plastic surgeons
using a composite subjective visual analogue score (VAS). RESULTS: Photographic
follow-up was 27 months (range, 10-60 months). Botulinum toxin type A was
assigned to the upper forehead in 16 cases and lower forehead in 10 cases.
Intrarater reliability among 4 evaluators of 104 VAS scores was 78.1%. Upper
forehead VAS (7.9 +/- 1.2) was not different than lower forehead VAS (7.9 +/-
1.2) regardless of treatment (P = 0.62). The VAS score of BTX-A-treated scars
(8.5 +/- 1.0) was significantly higher than the control (7.3 +/- 1.1; P <
0.0001). Among 104 individual comparisons (26 patients * 4 observers), there were
73 instances (70.2%) where the experimental VAS score was higher than the
control. CONCLUSIONS: Preoperative BTX-A injection is feasible and enhances donor
site scar appearance after forehead flap nasal reconstruction in an Asian
population.
PMID- 26418785
TI - Breast Reconstruction Using the Geometrically Modified Profunda Artery Perforator
Flap From the Posteromedial Thigh Region: Combining the Benefits of Its
Predecessors.
AB - BACKGROUND: Occasionally, the deep inferior epigastric perforator flap is
unavailable for autologous breast reconstruction. Alternative options, such as
gluteal artery perforator flaps, the transverse upper gracilis flap, and the
profunda artery perforator (PAP) flap, have been well documented. In our initial
experience, the PAP flap was associated with limitations at the donor site.
Therefore, a geometrically modified PAP flap was evaluated. METHODS: Forty
geometrically modified PAP flap reconstructions were performed on 30 patients.
Our modification comprised flap harvest from a more cranial area, hereby adding
abundant inferior gluteal tissue to the flap while sparing superior thigh tissue.
Patient characteristics, anatomical variables, and clinical outcome were
prospectively evaluated. RESULTS: Mean patient age was 44 years, and mean body
mass index (BMI) was 23.3 kg/m. Mean flap size was 32 * 12 cm, and mean weight
was 385 g. Mean number of suitable perforators (diameter >= 0.5 mm) in the
adductor magnus area was 1.7 per thigh. All flaps survived completely. Wound
dehiscence at the donor site occurred after 4 unilateral reconstructions.
Transient lymphedema of the leg occurred after 4 other unilateral
reconstructions. Other wound morbidity or systemic complications did not occur.
Secondary breast surgery for symmetry and volume was indicated after 16
reconstructions. Preoperative bra size was unchanged or larger in 36
reconstructions. Scar position in the crease was achieved after 39
reconstructions. Sensibility changes of the posteromedial thigh region were not
observed. CONCLUSIONS: The geometrically modified PAP flap ensures in-the-crease
scar positioning and provides sufficient tissue to restore preoperative bra size.
PMID- 26418786
TI - Effects of High-Voltage Electrical Stimulation in Improving the Viability of
Musculocutaneous Flaps in Rats.
AB - BACKGROUND: The musculocutaneous flap of the transverse rectus abdominis muscle
is a technique used for breast reconstruction, and one of the complications of
this procedure is tissue necrosis. The objective of the study is to determine the
effect of high-voltage electrical stimulation (HVES) in the transverse rectus
abdominis muscle flap in rats. METHODS: Fourteen rats underwent surgery for
obtaining the flap. The rats were distributed into 2 homogeneous groups: group 1
underwent both surgery and the use of HVES, whereas group 2 underwent just the
surgery (control). Electrical stimulation was applied immediately after surgery
and for 2 consecutive days. The percentage of necrotic area was analyzed using
the Image J software, and blood flow was assessed by infrared thermography in
different regions of the flap, divided into 4 zones according to the proximity of
the pedicle of the inferior epigastric artery. RESULTS: The results were analyzed
using a Student t test, where group 1 experienced a necrotic area of 26.2%, and
group 2 had an area of 54.5%. Regarding the temperature, the 2 groups showed
increase in the minimum and maximum temperature on the fourth postoperative day.
CONCLUSION: The HVES appeared to have a positive influence on the viability of
the flap.
PMID- 26418788
TI - Validation of Videoconference With Smartphones in Telemedicine Facial Trauma
Care: Analysis of Concordance to On-Site Evaluation.
AB - BACKGROUND: The continental size of some countries and heterogeneous hospital
network prevents patients who live in remote areas from getting adequate initial
assessment of facial trauma. The authors present an alternative model for trauma
assessment by videoconference via smartphones and analyze the concordance between
telemedicine and face-to-face management. METHODS: Fifty patients with either a
confirmed or suspected diagnosis of facial trauma were independently evaluated by
2 teams of physicians: Face-to-face and telemedicine-based. The face-to-face team
attended patients at bedside (physical examination and computed tomography scan
analysis). The telemedicine team consisted of a general surgery resident on duty
in the emergency room and a plastic surgeon researcher remotely communicating via
smartphones. Both teams answered a questionnaire, which contained data concerning
patient's epidemiology, physical examination, computed tomography (CT) scan
findings, and treatment option to be followed. Data were analyzed and compared
regarding the similarity of answers. RESULTS: The sample studied was consistent
with the literature, showing a predominance of young males. Traffic accidents and
personal violence were the main causes of trauma. The concurrency of answers for
physical examination findings was considered substantial (kappa = 0.720). For CT
scan findings, it was almost perfect (kappa = 0.899); for defining the treatment
option, it was almost perfect (kappa = 0.891). High concurrency of face CT scan
findings was observed after we calculated the positive predictive value (89.9%),
negative predictive value (99.3%), sensitivity (94.2%), specificity (98.8%), and
accuracy (98.3%). CONCLUSIONS: The proposed model to facial assessment trauma by
videoconference via smartphones is feasible, showing high concordance level with
face-to-face assessment.
PMID- 26418787
TI - Changes in Skin Vascularity in a Murine Model for Postmastectomy Radiation.
AB - BACKGROUND: Postmastectomy radiation causes persistent injury to the breast
microvasculature, and the prevailing assumption is that longer delays before
breast reconstruction allow for recovery of blood supply. This study uses a
murine model to examine the effects of radiation on skin vascularity to help
determine when radiation-induced effects on the microvasculature begin to
stabilize. STUDY DESIGN: Isogenic Lewis rats were divided into 2 groups:
radiation therapy (XRT) (n = 24) and control (n = 24). The XRT rats received a
breast cancer therapy human dose-equivalent of radiation to the groin, whereas
control rats received no radiation. Animals were sacrificed at 4, 8, 12, and 16
weeks after completion of radiation. The vasculature was injected with Microfil,
and groin skin was harvested for radiomorphometric analysis by microcomputed
tomography. One-way analysis of variance with post hoc Tukey tests was used to
determine significance between groups. RESULTS: Augmentation in vascularity was
observed in the XRT group at 4 weeks after radiation compared to the control
group (P = 0.045). Vessel number was decreased at 12 weeks (P = 0.002) and at 16
weeks (P = 0.001) in the XRT rats compared to control rats. Vessel separation in
the XRT group was higher than that in the control group at 12 weeks (P = 0.009)
and 16 weeks (P = 0.001). There was no change in vessel number and separation
between weeks 12 and 16. CONCLUSIONS: A period of augmented skin vascularity is
seen after radiation injury followed by decreased vascularity which demonstrates
stabilization at approximately 12 weeks in this murine model. This model can be
used to further study breast flap vascularity and the optimization of the timing
of delayed breast reconstruction.
PMID- 26418789
TI - An Updated View of the Integrated Plastic Surgery Match.
AB - BACKGROUND: Plastic surgery is one the most competitive residency programs. Data
on match trends for plastic surgery residencies and traits of successful
applicants are necessary for individuals applying into this highly desirable
specialty. AIM: Analyze recent trends in the independent and integrated match as
well as to describe attributes of successful applicants. METHODS: Data from
National Resident Matching Program and San Francisco Match Program for 2007 to
2014 were compiled and analyzed. Statistical analysis and figure creation were
performed using the R software package. For bivariate associations, chi or
Fisher's exact test was used. RESULTS: The number of available integrated plastic
surgery positions through National Resident Matching Program has increased since
2007, whereas the number of independent residencies offered through the SF Match
has steadily decreased. The average Step 2 scores, The number of research
presentations, publications, abstracts, and the percent of students ranking
plastic surgery only have increased. In a break from previous trends, percent of
applicants with Alpha Omega Alpha (AOA) membership and mean Step 1 board scores
decreased. United States medical school applicants who matched were more likely
to be AOA members and graduates from a top 40 medical school. There was no
significant association between having an additional academic degree and
successfully matching into integrated plastic surgery. CONCLUSIONS: Integrated
plastic surgery residency programs continue to be highly competitive, with
overall increasing research experience, but slightly lower Step 1 scores and AOA
membership than that in previous years. If the trend of decreasing independent
and increasing integrated positions continues, the applicant only interested in
plastic surgery may find the integrated pathway a more feasible option.
PMID- 26418790
TI - Comment on the Chaput et al Study, Professional Burnout Among Plastic Surgery
Residents: Can it be Prevented? Outcomes of a National Survey.
PMID- 26418791
TI - Intraoperative Hemifacial Composite Flap Perfusion Assessment Using Spatial
Frequency Domain Imaging: A Pilot Study in Preparation for Facial
Transplantation.
AB - BACKGROUND: Vascularized composite allotransplantation represents an important
advancement in the field of reconstructive microsurgery and has continued to
increase in popularity. The significant clinical morbidity associated with flap
failure represents an important barrier to even more widespread use of these
techniques. Early identification of vascular compromise has been associated with
a higher salvage rate, yet most surgeons rely only on clinical assessment
intraoperatively. Spatial frequency domain imaging (SFDI) presents a noncontact,
objective measurement of tissue oxygenation over a large field of view. This
study aims to evaluate the use of SFDI technology in hemifacial composite flap
compromise as could occur during facial transplant. METHODS: Six composite
hemifacial flaps were created in three 35-kg Yorkshire pigs and continuously
imaged using SFDI before, during, and after 15-minute selective vascular pedicle
occlusion. Arterial and venous clamping trials were performed for each flap.
Changes in oxyhemoglobin concentration, deoxyhemoglobin concentration, and total
hemoglobin were quantified over time. RESULTS: The SFDI successfully measured
changes in oxygenation parameters in all 6 composite tissue flaps. Significant
changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin were seen
relative to controls. Early and distinct patterns of alteration were noted in
arterial and in venous compromise relative to one another. CONCLUSIONS: The need
for noninvasive, reliable assessment of composite tissue graft viability is
apparent, given the morbidity associated with flap failure. The results of this
study suggest that SFDI technology shows promise in providing intraoperative
guidance with regard to pedicle vessel integrity during reconstructive
microsurgery.
PMID- 26418793
TI - Reconstruction of a Large External Hemipelvectomy Defect After Chordoma Resection
Using a 5-Component Chimeric Rotational Flap: Reply.
PMID- 26418792
TI - The Surgical Treatment of Robin Sequence.
AB - BACKGROUND: We present an outcomes analysis of the surgical treatment of Robin
sequence including all infants and comorbid conditions treated by tongue-lip
adhesion (TLA) or mandibular distraction osteogenesis (MDO). METHODS: A 19-year
single-institution, multisurgeon retrospective review of all syndromic and
nonsyndromic neonates with Robin sequence treated with TLA (1994-2004) or MDO
(2004-2013) was performed. Comorbid conditions were recorded in all patients.
Outcomes include incidence of tracheostomy, improvement in obstructive breathing,
and surgical complications. Need for repeat distraction and conversion from TLA
to MDO were included as secondary end-points. Polysomnography data were recorded
preoperatively at 1 month and 1 year as a measure of airway improvement. RESULTS:
Seventy-four MDO patients and 15 TLA patients during the study period met
inclusion criteria. There was no significant difference in mean age at
intervention (32.1 +/- 29.0 vs 35.5 +/- 32.1 days), birth weight (2.9 +/- 0.7 vs
3.2 +/- 0.6 kg), prematurity (23.0 vs 35.7%), or intrauterine growth restriction
(31.1 vs 15.4%). Central nervous system anomalies (24.3% vs 0.0%; P < 0.04) and
gastrostomy tubes (66.2% vs 33.3%; P < 0.03) were present more frequently in MDO
patients versus TLA patients. Rates of other organ system anomalies were similar
between the groups. The success rate was significantly higher in the MDO group
(90.5% vs 60.0%; P < 0.008). Postoperative tracheostomies occurred in 8.1% of the
MDO group and 33.3% of the TLA group (P < 0.02). Preoperative apnea-hyponea index
was similar between the two groups (38.3 vs 38.1). The apnea-hyponea index was
significantly improved in the MDO group at 1 month (4.0 vs 21.7; P < 0.002) and 1
year (5.7 vs 20.5; P < 0.005). Surgical complications were statistically less in
the MDO group (20.3 vs 53.3%; P < 0.02). CONCLUSIONS: In the heterogeneous
population of Robin sequence, MDO demonstrates superior outcomes measures at 1
month and 1 year compared to TLA. Fewer complications occurred in the MDO group
compared to the TLA.
PMID- 26418794
TI - Systematic Reviews in Craniofacial Trauma-Strengths and Weaknesses.
AB - BACKGROUND: Despite substantial advances in the management of craniofacial
trauma, numerous clinical questions remain. These are increasingly being answered
using systematic reviews (SRs). However, caution is warranted as their validity
and role in influencing clinical practice has been called into question. METHODS:
A PubMed search was performed in October 2014 to identify SRs published up to and
including September 2014 in 35 scientific journals. Two authors independently
reviewed the literature and extracted data from included studies. Discrepancies
were resolved by consensus. Assessment of multiple systematic reviews (AMSTAR)
was used to determine the quality of SRs. RESULTS: The initial search retrieved
3080 articles of which 3051 articles were excluded after screening title and
abstract. After full-text review of the remaining 29 articles, 3 additional
articles were excluded, thus, leaving 26 SRs for final analysis. Regression
analysis demonstrated that the overall number of published SRs increased
significantly throughout the period analyzed (P = 0.022). The median AMSTAR score
of all SRs was 4.5, consistent with a "poor-to-fair" quality. The interobserver
agreement was high, as evidenced by a mean kappa of 0.91. Although there appeared
to be a trend toward an increase in AMSTAR score by year over the period
analyzed, this failed to reach statistical significance in terms of median (P =
0.36) or absolute (P = 0.26) counts. CONCLUSIONS: A tremendous opportunity exists
for improvements in the quality of SRs focusing on craniofacial trauma. In
addition to familiarizing authors with quality criteria for SRs, adoption of
strict reporting criteria by scientific journals may result in long-term
improvements in the quality of reporting.
PMID- 26418795
TI - Speech Outcomes After Clinically Indicated Posterior Pharyngeal Flap Takedown.
AB - BACKGROUND: Velopharyngeal insufficiency affects as many as one in three patients
after cleft palate repair. Correction using a posterior pharyngeal flap (PPF) has
been shown to improve clinical speech symptomatology; however, PPFs can be
complicated by hyponasality and obstructive sleep apnea. The goal of this study
was to assess if speech outcomes revert after clinically indicated PPF takedown.
METHODS: The cleft-craniofacial database of the Children's Hospital of Pittsburgh
at the University of Pittsburgh Medical Center was retrospectively queried to
identify patients with a diagnosis of velopharyngeal insufficiency treated with
PPF who ultimately required takedown. Using the Pittsburgh Weighted Speech Score
(PWSS), preoperative scores were compared to those after PPF takedown. Outcomes
after 2 different methods of PPF takedown (PPF takedown alone or PPF takedown
with conversion to Furlow palatoplasty) were stratified and cross-compared.
RESULTS: A total of 64 patients underwent takedown of their PPF. Of these, 18
patients underwent PPF takedown alone, and 46 patients underwent PPF takedown
with conversion to Furlow Palatoplasty. Patients averaged 12.43 (range, 3.0
22.0)(SD: 3.93) years of age at the time of PPF takedown, and 58% were men.
Demographics between groups were not statistically different. The mean duration
of follow-up after surgery was 38.09 (range, 1-104) (SD, 27.81) months. For
patients undergoing PPF takedown alone, the mean preoperative and postoperative
PWSS was 3.83 (range, 0.0-23.0) (SD, 6.13) and 4.11 (range, 0.0-23.0) (SD, 5.31),
respectively (P = 0.89). The mean change in PWSS was 0.28 (range, -9.0 to 7.0)
(SD, 4.3). For patients undergoing takedown of PPF with conversion to Furlow
palatoplasty, the mean preoperative and postoperative PWSS was 6.37 (range, 0-26)
(SD, 6.70) and 3.11 (range, 0.0-27.0) (SD, 4.14), respectively (P < 0.01). The
mean change in PWSS was -3.26 (range, -23.0 to 4.0) (SD, 4.3). For all patients,
the mean preoperative PWSS was 5.66 (range, 0.0-26) (SD, 6.60) and 3.39 (range,
0.0-27) (SD, 4.48), respectively (P < 0.05). The mean change in PWSS was -2.26
(range, -23.0 to 7) (SD, 5.7). There was no statistically significant regression
in PWSS for either surgical intervention. Two patients in the PPF takedown alone
cohort demonstrated deterioration in PWSS that warranted delayed conversion to
Furlow palatoplasty. Approximately 90% of patients, who undergo clinically
indicated PPF takedown alone, without conversion to Furlow Palatoplasty, will
show no clinically significant reduction in speech. CONCLUSIONS: Although there
is concern that PPF takedown may degrade speech, this study finds that surgical
takedown of PPF, when clinically indicated, does not result in a clinically
significant regression of speech.
PMID- 26418796
TI - Do Wound Cultures Give Information About the Microbiology of Blood Cultures in
Severe Burn Patients?
AB - BACKGROUND: Blood stream infection (BSI) and the subsequent development of sepsis
are among the most common infection complications occurring in severe burn
patients. This study was designed to evaluate the relationship between the burn
wound flora and BSI pathogens. METHODS: Documentation of all bacterial and fungal
wound and blood isolates from severe burn patients hospitalized in the burn unit
and intensive care unit was obtained from medical records retrieved
retrospectively from a computerized, hospital-wide database over a 13-year
period. All data were recorded in relation to the Ryan score. RESULTS: Of 195
severe burn patients, 88 had at least 1 BSI episode. Transmission of the same
pathogen from wound to blood was documented in 30% of the patients, with a rising
BSI frequency as the Ryan score increased. There were a total of 263 bacteremic
episodes in 88 study patients, 44% of blood isolates were documented previously
in wound cultures, and transmission of the same pathogen from wound to blood was
noted in 65% of bacteremic patients. CONCLUSIONS: When there is clinical
suspicion of sepsis, appropriate empirical systemic antibiotic therapy should be
broad spectrum and should rely on the susceptibility of the organisms from recent
cultures of the burn wound surface, until the blood cultures results are
completed.
PMID- 26418797
TI - Status of Microsurgical Simulation Training in Plastic Surgery: A Survey of
United States Program Directors.
AB - PURPOSE: Various simulation models for microsurgery have been developed to
overcome the limitations of Halstedian training on real patients. We wanted to
assess the status of microsurgery simulation in plastic surgery residency
programs in the United States. METHODS: Data were analyzed from responses to a
survey sent to all plastic surgery program directors in the United States, asking
for type of simulation, quality of facilities, utilization by trainees,
evaluation of trainee sessions, and perception of the relevance of simulation.
RESULTS: The survey response rate was 50%. Of all programs, 69% provide
microsurgical simulation and 75% of these have a laboratory with microscope and
52% provide live animal models. Half share facilities with other departments. The
quality of facilities is rated as good or great in 89%. Trainee utilization is
once every 3 to 6 months in 82% of programs. Only in 11% is utilization monthly.
Formal evaluation of simulation sessions is provided by 41% of programs. All
program directors agree simulation is relevant to competence in microsurgery, 60%
agree simulation should be mandatory, and 43% require trainees to complete a
formal microsurgery course prior to live surgery. DISCUSSION: There seems to be
consensus that microsurgical simulation improves competence, and the majority of
program directors agree it should be mandatory. Developing and implementing
standardized simulation modules and assessment tools for trainees across the
nation as part of a comprehensive competency-based training program for
microsurgery is an important patient safety initiative that should be considered.
Organizing with other departments to share facilities may improve their quality
and hence utilization.
PMID- 26418798
TI - Improvement of Split Skin Graft Quality Using a Newly Developed Collagen Scaffold
as an Underlayment in Full Thickness Wounds in a Rat Model.
AB - INTRODUCTION: Frequently, full thickness skin defects were treated through split
skin graft (SSG) transplantation. However, this is usually associated with a
reduction of skin quality and scarring. In this context, a newly developed
collagen cell carrier (CCC) has been evaluated as an underlayment in SSG
transplantations in a rat model. MATERIALS AND METHODS: Twenty-eight standardized
full thickness skin defects were generated on the back of 28 adult male Lewis
rats. The wounds were randomized and treated with SSG transplantation solitarily
(n = 14) or SSG transplantation using CCC as an underlayment (n = 14). For skin
quality analysis, a histological evaluation was performed 3 months postoperative
in regard to epidermal cell count and epidermal and dermal thickness. RESULTS:
Wounds treated with SSG and CCC demonstrated a thicker epidermis and
significantly higher epidermal cell count compared to SSG solitarily. At the time
of evaluation, epidermal thickness of SSG and CCC was comparable to untreated,
healthy skin (no statistically significant differences). DISCUSSION: As split
skin grafting is frequently associated with skin quality reduction, the presented
results reveal the beneficial effects of CCC in terms of skin graft quality
improvement. This may offer unique opportunities in wound management and
encourages further evaluation of CCC in surgical applications and regenerative
medicine.
PMID- 26418799
TI - Botulinum Toxin Use in Pediatric Plastic Surgery.
AB - Botulinum toxin has increasingly become a prevalent treatment option for a wide
range of conditions, many of which have their roots in plastic surgery and have
been well studied. In adults, chronic headache, hyperhidrosis, and facial
muscular hypertrophy have been effectively treated with botulinum toxin, and
emerging studies have begun looking at its efficacy in children, as well.
Successful treatment of spasticity and muscular contraction has allowed for the
creation of safety profiles and dosage guidelines for botulinum toxin usage in
children. The expanded indications for its use have since flourished in all
arenas of pediatric care, including plastic surgery. Recent studies have
described the use of botulinum toxin as an adjunct to the treatment of congenital
torticollis and cleft lip. This review discusses the various applications of
botulinum toxin for pediatric patients in the field of plastic surgery.
PMID- 26418800
TI - Strategies for the Optimal Individualized Surgical Management of Craniofacial
Fibrous Dysplasia.
AB - BACKGROUND: The surgical management of craniofacial fibrous dysplasia is
controversial. The purpose of this study was to report the surgical outcomes of
individualized management of craniofacial fibrous dysplasia of a single
institution. METHODS: Data from patients (n = 20) with craniofacial fibrous
dysplasia, who were surgically treated between 2007 and 2014, were analyzed.
Surgical approach (radical or conservative surgery) was individualized according
to age, craniofacial anatomical site (zones I to IV of Chen and Noordhoff),
functional issues, aesthetic impairment, patients/parents' preferences, and
surgical team experience. The surgical outcomes (radical surgery group versus
conservative surgery group) were compared based on the age at the time of the
procedure, the length of hospital stay, reoperation, recurrence and complication
rates, and the Whitaker grading system. RESULTS: Significant (all P < 0.05)
differences were observed in patients with craniofacial fibrous dysplasia who
were treated with radical excision (65%) compared with those treated with limited
reduction burring (35%), according to age (19.22 years versus 12.57 years), the
length of hospital stay (3.56 days versus 1.29 days), recurrence (15% versus
71%), and number of subsequent procedures (1 intervention versus 2.4
interventions), respectively. The radical surgery group presented a significantly
(P < 0.05) lower initial Whitaker outcome score than the conservative surgery
group (1.89 and 2.57, respectively). Similar (all P > 0.05) final Whitaker
outcome scores (1.56 versus 1.71) and surgical complication rates (11% versus
14%) were recorded between the treatment groups. CONCLUSIONS: Based on clinical
experience and surgical outcomes presented in this study, the surgical approach
of craniofacial fibrous dysplasia should be tailored to individual patient's
needs.
PMID- 26418803
TI - Autologous Fat Grafting With Combined Three-Dimensional and Mirror-Image Analyses
for Progressive Hemifacial Atrophy.
AB - BACKGROUND: Autologous fat grafting (AFG) has been widely used to treat
progressive hemifacial atrophy (PHA). However, objective and quantitative
analyses in patients with PHA are complicated because of multidimensional atrophy
and fat absorption. This study aimed to introduce a new method to predict
volumetric deficiency of soft tissues and objectively evaluate the survival of
grafted fat with 3-dimensional (3D) and mirror-image analysis (MIA). METHODS:
Thirty-one patients with PHA were classified into 2 groups based on the location
of the facial midsagittal plane (FMP), which was established through our proposed
method using nasion (point a), anterior nasal spine (point b), and pogonion
(point c). The included cases with centered FMP were treated using serial AFG and
followed up for 12 to 15 months. Images were obtained preoperatively (pre-OP) and
postoperatively at 2 time points (3 months and 12 months). Three-dimensional
computed tomography (CT) was performed before the first surgery to locate the FMP
and predict the volumetric deficiency of soft tissues with MIA. Three months
after the first surgery, 3D laser scanning was conducted to evaluate the volume
of surviving fat. Patient characteristics, satisfaction, and soft tissue
augmentation results were analyzed. RESULTS: Twenty-seven cases (9 men and 18
women) with PHA were included and treated using serial AFG (mean number of
operation, 3.1 times). The mean age was 22.1 years. With 3D CT or 3D laser
scanning camera and MIA, we obtained the mean deficient volume of the affected
area (30.48 mm) and the mean volume of the total fat injection (133.61 mm). The
mean fat absorption ratio was 47.92%. The mean satisfaction score immediately
obtained at first postoperative (score = 4.3) was higher than that at 3 months
postoperatively (score = 4.1) and 12 months postoperatively (score = 4.0). No
complications and donor-site morbidity were noted. CONCLUSION: The facial
symmetry of patients with centered FMP can be successfully restored using serial
AFG alone. The combined 3D and MIA can be used to predict the volumetric
deficiency of soft tissues and objectively evaluate the survival of grafted fat.
PMID- 26418804
TI - Reconstruction of a Nose Bitten and Eaten by a Dog: A Ten-Year Follow-up of a
Bitten-Off Nose Replantation Performed on an Eleven-Year-Old Boy.
AB - The nose is one of the most important aesthetic units of the face. After a
traumatic amputation, replantation is undoubtedly the procedure of choice,
although, technically, very challenging. We report the 10-year follow-up of a
partially digested nose replantation after a dog-bite in an 11-year-old boy using
supermicrosurgery technique. Our report confirms that the microsurgical
replantation of the nose can lead to an acceptable aesthetic result, with the
sufficient growth of the replanted part in the following years. Besides the
patient did not report sensibility disorders. The nose replantation in our
opinion is the best reconstructive option to achieve an optimal aesthetic and
functional outcome.
PMID- 26418805
TI - A Standardized Method of Isolating Adipose-Derived Stem Cells for Clinical
Applications.
AB - White adipose tissue is the most abundant and accessible source of stem cells in
the adult human body. In this paper, we present a standardised and safe method of
isolating and maximizing the number of adipose-derived stem cells (ASCs) from
conventional liposuction for clinical applications, which was carried out through
both mechanical (centrifuge) and enzymatic (collagenase) means. Isolated cells
were characterized through flow cytometry assay. Gathered data showed a greater
amount (9.06 * 10(5) ASCs from 100 mL of adipose tissue) of isolated ASCs
compared to previous protocol, also with high (99%) cell vitality; the procedure
we presented is easy and fast (80 minutes), allowing collecting a significative
number of mesenchymal stem cells, which can be used for clinical purposes, such
as wound healing.
PMID- 26418806
TI - Differences in the Postoperative Outcomes According to the Primary Treatment
Options Chosen by Patients With Carpal Tunnel Syndrome: Conservative Versus
Operative Treatment.
AB - PURPOSE: We prospectively analyzed the differences in the preoperative status and
final outcomes between patients with or without the motivation for prompt surgery
after a recent diagnosis of carpal tunnel syndrome (CTS). METHODS: One hundred
fifty-six patients were enrolled and followed up from a cohort of 220 patients
who were diagnosed with CTS between 2011 and 2013. Basic demographic factors,
including the occupational features, were investigated in group 1 (n = 52,
conservative treatment followed by surgery) and group 2 (n = 100, surgery
immediately after diagnosis). The preoperative electrodiagnosis, clinical items
by Graham, Disabilities of the Arm, Shoulder, and Hand (DASH) outcomes
questionnaire, Boston Carpal Tunnel Questionnaire scores, and grip/pinch
strengths were evaluated, and the degree of improvements was compared. RESULTS:
The onset period of the symptoms or signs, as well as the time from the diagnosis
to surgery, was significantly longer in group 1 than in group 2. In group 1,
nonprofessional, simple, and repetitive jobs were more prevalent; however, the
professional category was more common in group 2. The preoperative distributions
among the electrodiagnostic grades were not different in both groups. Most of the
clinical items by Graham were more definitively improved in group 2. DASH
improvement at the final follow-up was meaningfully more in group 2 (34 +/- 5.3)
than in group 1 (29 +/- 6.5). Boston Carpal Tunnel Questionnaire showed a similar
trend regarding the DASH score (preoperative, improvement at the final follow-up)
with statistical significance. The increase in grip/pinch strength was also
greater in group 2. CONCLUSIONS: Most patients, who refused/delayed surgery as
the initial treatment for CTS, were not improved by conservative options.
Eventually, carpal tunnel release was performed; however, the overall outcomes
were inferior compared with those of the groups who agreed to operative treatment
as the initial option.
PMID- 26418807
TI - Characterization and exposure measurement for indium oxide nanofibers generated
as byproducts in the LED manufacturing environment.
AB - This article aimed to elucidate the physicochemical characteristics and exposure
concentration of powder and airborne particles as byproducts generated from
indium tin oxide thin film process by an electron beam evaporation method during
maintenance in light-emitting diode manufacturing environment. The chemical
composition, size, shape, and crystal structure of powder and airborne particles
as byproducts were investigated using a scanning electron microscope equipped
with energy dispersive spectrometer, and an X-ray diffractometer. The number and
mass concentration measurements of airborne particles were performed by using an
optical particle counter of direct-reading aerosol monitor and an inductively
coupled plasma-mass spectrometry after sampling, respectively. The airborne
particles are composed of oxygen and indium. On the other hand, the powder
byproducts consist mostly of oxygen and indium, but tin was found as a minor
component. The shapes of the airborne and powder byproducts were fiber type. The
length and diameter of fibrous particles were approximately 500-2,000 nm and 30
50 nm, respectively. The powder byproducts indicated indium oxide nanofibers with
a rhombohedral structure. On the other hand, the indium oxide used as a source
material in the preparation of ITO target showed spherical morphology with a body
centered cubic structure, and it was the same as that of the pure crystalline
indium oxide powder. During maintenance, the number concentrations ranged from
350-75,693 particles/ft(3), and arithmetic mean+/-standard deviation and
geometric mean+/-geometric standard deviation were 11,624+/-15,547 and 4,846+/
4.12 particles/ft(3), respectively. Meanwhile, under the same conditions, the
airborne mass concentrations of the indium based on respirable particle size (3.5
um cut-point 50%) were 0.09-0.19 ug/m(3). Physicochemical characteristics of
nanoparticle can affect toxicity so the fact that shape and crystal structure
have changed is important. Thus, nanoparticle occupational toxicology greatly
needs observations like this.
PMID- 26418808
TI - Fucoxanthin Inhibits the Inflammation Response in Paw Edema Model through
Suppressing MAPKs, Akt, and NFkappaB.
AB - Undaria pinnatifida is a well-known traditional Korean food with a variety of
biological activities. Carrageenan (carr) is commonly used to induce paw edema in
animal models. This study was designed to elucidate the processes underlying the
anti-inflammatory effect of fucoxanthin isolated from the sporophyll of U.
pinnatifida in carr-induced paw edema in ICR mice. Fucoxanthin significantly
decreased carr-induced increased nitric oxide levels in the plasma of mice with
carr-induced paw edema. Fucoxanthin protected catalase (CAT) and superoxide
dismutase (SOD) activity against disruption in mice with carr-induced paw edema.
In addition, fucoxanthin repressed carr-induced activation of inducible nitric
oxide synthase, cyclooxygenase-2, and nuclear factor kappa B, as well as carr
induced phosphorylation of mitogen-activated protein kinase, extracellular signal
regulated kinase, c-Jun N-terminal kinase, p38, and protein kinase B/Akt. These
results suggest that fucoxanthin may have therapeutic potential as a treatment
for patients with inflammatory diseases.
PMID- 26418809
TI - Coexisting Membranous Nephropathy and IgA Nephropathy.
AB - We herein present a case of a 14-year-old boy with the histological features of
coexisting membranous nephropathy (MN) and IgA nephropathy (IgAN). Asymptomatic
hematuria/proteinuria was initially detected in school urinary screening, with
treatments including oral corticosteroids leading to complete remission. Cases of
coexisting MN and IgAN are very rare among the pediatric population; however, the
overlap of these two nephropathies does not always imply a deleterious clinical
outcome in pediatric cases.
PMID- 26418810
TI - Evidence of Notch-Hesr-Nrf2 Axis in Muscle Stem Cells, but Absence of Nrf2 Has No
Effect on Their Quiescent and Undifferentiated State.
AB - Nrf2 is a master regulator of oxidative stresses through the induction of anti
oxidative genes. Nrf2 plays roles in maintaining murine hematopoietic stem cells
and fly intestinal stem cells. The canonical Notch signaling pathway is also
crucial for maintaining several types of adult stem cells including muscle stem
cells (satellite cells). Here, we show that Dll1 induced Nrf2 expression in
myogenic cells. In addition, primary targets of Notch signaling, Hesr1 and Hesr3,
were involved in the up-regulation of Nrf2 mRNA and expression of its target
genes. In vitro, Nrf2 had anti-myogenic and anti-proliferative effects on primary
myoblasts. In vivo, although Nrf2-knockout mice showed decreased expression of
its target genes in muscle stem cells, adult muscle stem cells of Nrf2-knockout
mice did not exhibit the phenotype. Taken together, in muscle stem cells, the
Notch-Hesr-Nrf2 axis is a pathway potentially inducing anti-oxidative genes, but
muscle stem cells either do not require Nrf2-mediated anti-oxidative gene
expression or they have a complementary system compensating for the loss of Nrf2.
PMID- 26418811
TI - Expanding Functionality of Commercial Optical Coherence Tomography Systems by
Integrating a Custom Endoscope.
AB - Optical coherence tomography (OCT) is a useful imaging modality for detecting and
monitoring diseases of the gastrointestinal tract and other tubular structures.
The non-destructiveness of OCT enables time-serial studies in animal models.
While turnkey commercial research OCT systems are plenty, researchers often
require custom imaging probes. We describe the integration of a custom endoscope
with a commercial swept-source OCT system and generalize this description to any
imaging probe and OCT system. A numerical dispersion compensation method is also
described. Example images demonstrate that OCT can visualize the mouse colon
crypt structure and detect adenoma in vivo.
PMID- 26418812
TI - Layer-by-Layers of Polymeric Micelles as a Biomimetic Drug-Releasing Network.
AB - Mucin networks are lubricous biofunctional coats formed through the continuous
deposition of mucin glycoproteins. Previously, we demonstrated the synthesis of a
mucin mimic using biotinylated-filomicelles crosslinked via streptavidin using a
layer-by-layer approach. These networks recreate the fibrous nature of mucin and
can serve as a drug-releasing network. In this work, the ability to vary the
network properties by blending filomicelles with spherical micelles is
demonstrated. In addition, the deposition of a dense polymer coating on the mucin
network was shown to act as a barrier to control diffusion and improved the
structural stability under simulated oral chemical conditions. These biomimetic
coatings can be utilized as a delivery system, providing a tunable drug release
for oral applications.
PMID- 26418814
TI - Highly Regioselective Palladium-Catalyzed Carboxylation of Allylic Alcohols with
CO2.
AB - Various allylic alcohols were carboxylated in the presence of a catalytic amount
of PdCl2 and PPh3 using ZnEt2 as a stoichiometric transmetalation agent under a
CO2 atmosphere (1 atm). This carboxylation proceeded in a highly regioselective
manner to afford branched carboxylic acids predominantly. The beta,gamma
unsaturated carboxylic acid thus obtained was successfully converted into an
optically active gamma-butyrolactone, a known intermediate of (R)-baclofen.
PMID- 26418813
TI - Effectiveness of a Home-Based Counselling Strategy on Neonatal Care and Survival:
A Cluster-Randomised Trial in Six Districts of Rural Southern Tanzania.
AB - BACKGROUND: We report a cluster-randomised trial of a home-based counselling
strategy, designed for large-scale implementation, in a population of 1.2 million
people in rural southern Tanzania. We hypothesised that the strategy would
improve neonatal survival by around 15%. METHODS AND FINDINGS: In 2010 we trained
824 female volunteers to make three home visits to women and their families
during pregnancy and two visits to them in the first few days of the infant's
life in 65 wards, selected randomly from all 132 wards in six districts in Mtwara
and Lindi regions, constituting typical rural areas in Southern Tanzania. The
remaining wards were comparison areas. Participants were not blinded to the
intervention. The primary analysis was an intention-to-treat analysis comparing
the neonatal mortality (day 0-27) per 1,000 live births in intervention and
comparison wards based on a representative survey in 185,000 households in 2013
with a response rate of 90%. We included 24,381 and 23,307 live births between
July 2010 and June 2013 and 7,823 and 7,555 live births in the last year in
intervention and comparison wards, respectively. We also compared changes in
neonatal mortality and newborn care practices in intervention and comparison
wards using baseline census data from 2007 including 225,000 households and
22,243 births in five of the six intervention districts. Amongst the 7,823 women
with a live birth in the year prior to survey in intervention wards, 59% and 41%
received at least one volunteer visit during pregnancy and postpartum,
respectively. Neonatal mortality reduced from 35.0 to 30.5 deaths per 1,000 live
births between 2007 and 2013 in the five districts, respectively. There was no
evidence of an impact of the intervention on neonatal survival (odds ratio [OR]
1.1, 95% confidence interval [CI] 0.9-1.2, p = 0.339). Newborn care practices
reported by mothers were better in intervention than in comparison wards,
including immediate breastfeeding (42% of 7,287 versus 35% of 7,008, OR 1.4, CI
1.3-1.6, p < 0.001), feeding only breast milk for the first 3 d (90% of 7,557
versus 79% of 7,307, OR 2.2, 95% CI 1.8-2.7, p < 0.001), and clean hands for home
delivery (92% of 1,351 versus 88% of 1,799, OR 1.5, 95% CI 1.0-2.3, p = 0.033).
Facility delivery improved dramatically in both groups from 41% of 22,243 in 2007
and was 82% of 7,820 versus 75% of 7,553 (OR 1.5, 95% CI 1.2-2.0, p = 0.002) in
intervention and comparison wards in 2013. Methodological limitations include our
inability to rule out some degree of leakage of the intervention into the
comparison areas and response bias for newborn care behaviours. CONCLUSION:
Neonatal mortality remained high despite better care practices and childbirth in
facilities becoming common. Public health action to improve neonatal survival in
this setting should include a focus on improving the quality of facility-based
childbirth care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022788.
PMID- 26418815
TI - Novel sirtuin inhibitory warheads derived from the N(epsilon)-acetyl-lysine
analog L-2-amino-7-carboxamidoheptanoic acid.
AB - Built upon the catalytic mechanism-based pan-SIRT1/2/3 inhibitory warhead L-2
amino-7-carboxamidoheptanoic acid (L-ACAH, a close structural analog of
N(epsilon)-acetyl-lysine) that our laboratory discovered recently, in the current
study, its carboxamide NH2-ethylated analog was found to be a ~2.4-6.6-fold
stronger SIRT1/2/3 inhibitory warhead than L-ACAH. Carboxamide NH2-dodecylated
and carboxymethylated analogs of L-ACAH were also identified as potent SIRT6 and
SIRT5 inhibitory warheads, respectively.
PMID- 26418817
TI - Human Rights Texts: Converting Human Rights Primary Source Documents into Data.
AB - We introduce and make publicly available a large corpus of digitized primary
source human rights documents which are published annually by monitoring agencies
that include Amnesty International, Human Rights Watch, the Lawyers Committee for
Human Rights, and the United States Department of State. In addition to the
digitized text, we also make available and describe document-term matrices, which
are datasets that systematically organize the word counts from each unique
document by each unique term within the corpus of human rights documents. To
contextualize the importance of this corpus, we describe the development of
coding procedures in the human rights community and several existing categorical
indicators that have been created by human coding of the human rights documents
contained in the corpus. We then discuss how the new human rights corpus and the
existing human rights datasets can be used with a variety of statistical analyses
and machine learning algorithms to help scholars understand how human rights
practices and reporting have evolved over time. We close with a discussion of our
plans for dataset maintenance, updating, and availability.
PMID- 26418816
TI - Scalable Production of Recombinant Membrane Active Peptides and Its Potential as
a Complementary Adjunct to Conventional Chemotherapeutics.
AB - The production of short anticancer peptides in recombinant form is an alternative
method for costly chemical manufacturing. However, the limitations of host
toxicity, bioactivity and column purification have impaired production in mass
quantities. In this study, short cationic peptides were produced in aggregated
inclusion bodies by double fusion with a central protein that has anti-cancer
activity. The anticancer peptides Tachiplicin I (TACH) and Latarcin 1 (LATA) were
fused with the N- and C-terminus of the MAP30 protein, respectively. We
successfully produced the recombinant TACH-MAP30-LATA protein and MAP30 alone in
E. coli that represented 59% and 68% of the inclusion bodies. The purified form
of the inclusion bodies was prepared by eliminating host cell proteins through
multiple washing steps and semi-solubilization in alkaline buffer. The purified
active protein was recovered by inclusive solubilization at pH 12.5 in the
presence of 2 M urea and refolded in alkaline buffer containing oxides and
reduced glutathione. The peptide-fusion protein showed lower CC50 values against
cancer cells (HepG2, 0.35+/-0.1 MUM and MCF-7, 0.58+/-0.1 MUM) compared with
normal cells (WRL68, 1.83+/-0.2 MUM and ARPE19, 2.5+/-0.1 MUM) with outstanding
activity compared with its individual components. The presence of the short
peptides facilitated the entry of the peptide fusion protein into cancer cells
(1.8 to 2.2-fold) compared with MAP30 alone through direct interaction with the
cell membrane. The cancer chemotherapy agent doxorubicin showed higher efficiency
and selectivity against cancer cells in combination with the peptide- fusion
protein. This study provides new data on the mass production of short anticancer
peptides as inclusion bodies in E. coli by fusion with a central protein that has
similar activity. The product was biologically active against cancer cells
compared with normal cells and enhanced the activity and selective delivery of an
anticancer chemotherapy agent.
PMID- 26418818
TI - Unexpectedly Stable (Chlorocarbonyl)(N-ethoxycarbonylcarbamoyl)disulfane, and
Related Compounds That Model the Zumach-Weiss-Kuhle (ZWK) Reaction for Synthesis
of 1,2,4-Dithiazolidine-3,5-diones.
AB - The Zumach-Weiss-Kuhle (ZWK) reaction provides 1,2,4-dithiazolidine-3,5-diones
[dithiasuccinoyl (Dts)-amines] by the rapid reaction of O-ethyl thiocarbamates
plus (chlorocarbonyl)sulfenyl chloride, with ethyl chloride and hydrogen chloride
being formed as coproducts, and carbamoyl chlorides or isocyanates generated as
yield-diminishing byproducts. However, when the ZWK reaction is applied with (N
ethoxythiocarbonyl)urethane as the starting material, heterocyclization to the
putative "Dts-urethane" does not occur. Instead, the reaction directly provides
(chlorocarbonyl)(N-ethoxycarbonylcarbamoyl)disulfane, a reasonably stable
crystalline compound; modified conditions stop at the (chlorocarbonyl)[1-ethoxy
(N-ethoxycarbonyl)formimidoyl]disulfane intermediate. The title
(chlorocarbonyl)(carbamoyl)disulfane cannot be converted to the elusive Dts
derivative, but rather gives (N-ethoxycarbonyl)carbamoyl chloride upon
thermolysis, or (N-ethoxycarbonyl)isocyanate upon treatment with tertiary amines.
Additional transformations of these compounds have been discovered, providing
entries to both known and novel species. X-ray crystallographic structures are
reported for the title (chlorocarbonyl)(carbamoyl)disulfane; for
(methoxycarbonyl)(N-ethoxycarbonylcarbamoyl)disulfane, which is the corresponding
adduct after quenching in methanol; for [1-ethoxy-(N
ethoxycarbonyl)formimidoyl](N'-methyl-N'-phenylcarbamoyl)disulfane, which is
obtained by trapping the title intermediate with N-methylaniline; and for (N
ethoxycarbonylcarbamoyl)(N'-methyl-N'-phenylcarbamoyl)disulfane, which is a short
lived intermediate in the reaction of the title
(chlorocarbonyl)(carbamoyl)disulfane with excess N-methylaniline. The new
chemistry and structural information reported herein is expected to contribute to
accurate modeling of the ZWK reaction trajectory.
PMID- 26418819
TI - Predictive Factors Affecting Long-Term Outcome of Unilateral Lateral Rectus
Recession.
AB - BACKGROUND: There are few long-term outcome reports of unilateral lateral rectus
(LR) recession for exotropia including a large number of subjects. Previous
reports on unilateral LR recession commonly show extremely low rates of initial
overcorrection and large exodrifts after surgery suggesting that the surgical
dose may be increased. However, little is known of the long-term outcome of a
large unilateral LR recession for exotropia. OBJECTIVES: To determine long-term
outcomes and predictive factors of recurrence after a large unilateral LR
recession in patients with exotropia. DATA EXTRACTION: Retrospective analysis was
performed on 92 patients aged 3 to 17 years who underwent 10 mm unilateral LR
recession for exotropia of <= 25 prism diopters (Delta) with prism and alternate
cover testing and were followed up for more than 2 years after surgery. Final
success rates within 10Delta of exophoria/tropia and 5Delta of esophoria/tropia
at distance in the primary position, improvement in stereopsis and the predictive
factors for recurrence were evaluated. RESULTS: At 24 months after surgery, 54%
of patients had ocular alignment meeting the defined criteria of success, 45% had
recurrence and 1% had overcorrection. After a mean follow-up of 39 months, 36%
showed success, 63% showed recurrence and 1% resulted in overcorrection. The
average time of recurrence was 23.4+/-14.7 months (range, 1-60 months) and the
rate of recurrence per person-year was 23% after unilateral LR recession.
Predictive factors of recurrence were a larger preoperative near angle of
deviation (>16Delta) and larger initial postoperative exodeviation (>5Delta) at
distance. CONCLUSIONS: Long-term outcome of unilateral LR recession for exotropia
showed low success rates with high recurrence, thus should be reserved for
patients with a small preoperative near angle of exodeviation.
PMID- 26418820
TI - Asymmetric Construction of 3,4-Diamino Pyrrolidines via Chiral N,O-Ligand/Cu(I)
Catalyzed 1,3-Dipolar Cycloaddition of Azomethine Ylides with beta
Phthalimidonitroethene.
AB - A series of chiral N,O-ligands derived from a 1,2-dihydroimidazo[1,2-a]quinolone
motif have been evaluated for the asymmetric 1,3-dipolar cycloaddition of
azomethine ylides with a novel dipolarophile beta-phthalimidonitroethene. A newly
designed DHIPOH ligand 7c bearing 1-methyl and 4-iodo substituents was found to
have significant "synergistic steric effects" and consequently afforded the
corresponding 4-nitro-3-aminopyrrolidines with excellent diastereo- (dr up to
98:2) and enantio selectivities (ee up to 99%). Subsequent Raney Ni-catalyzed
reduction and deprotection of phthalyl led to the structurally and biologically
important 3,4-diaminopyrrolidines in a straightforward and efficient pathway.
PMID- 26418821
TI - An update on Curcuma as a functional food in the control of cancer and
inflammation.
AB - PURPOSE OF REVIEW: Curcumin, commonly known as turmeric, is a spice that comes
from the root Curcuma longa. The present article presents an update of new
studies of curcumin activities as tested in anticancer models from 2011 to 2015.
RECENT FINDINGS: Evidence from in-vitro and in-vivo research, together with
clinical trials conducted over the past few decades, substantiates the potential
of curcumin as an anticancer and anti-inflammatory agent. The development of
formulations of curcumin in the form of nanoparticles, liposomes, micelles, or
phospholipid complexes to enhance its bioavailability and efficacy are still in
the early stages. Clinical trials with curcumin indicate safety, tolerability,
and nontoxicity. However, the efficacy is questionable, based on the small
numbers of patients in each study. SUMMARY: The laboratory and the clinical
studies until 2011 were summarized in a review published in this journal. An
update of the new studies and knowledge from 2011 to March 2015 focuses on new
ways to overcome its low bioavailability and data from clinical trials.
PMID- 26418822
TI - Gluten-free and casein-free diets in the therapy of autism.
AB - PURPOSE OF REVIEW: The purpose of this study is to discuss the role of gluten
free and casein-free diets in the treatment of autism. RECENT FINDINGS: In a
recent UK survey, more than 80% of parents of children with autism spectrum
disorder reported some kind of dietary intervention for their child (gluten-free
and casein-free diet in 29%). When asked about the effects of the gluten-free and
casein-free diet, 20-29% of the parents reported significant improvements on the
autism spectrum disorder core dimensions. The findings of this study suggest
additional effects of a gluten-free and casein-free diet on comorbid problems of
autism such as gastrointestinal symptoms, concentration, and attention. The
findings of another recent investigation suggested that age and certain urine
compounds may predict the response of autism symptoms to a gluten-free and casein
free diet. Although these results need to be replicated, they highlight the
importance of patient subgroup analysis. Intervention trials evaluating the
effects of a gluten-free and casein-free diet on autistic symptoms have so far
been contradictory and inconclusive. SUMMARY: Most investigations assessing the
efficacy of a gluten-free and casein-free diet in the treatment of autism are
seriously flawed. The evidence to support the therapeutic value of this diet is
limited and weak. A gluten-free and casein-free diet should only be administered
if an allergy or intolerance to nutritional gluten or casein is diagnosed.
PMID- 26418823
TI - Micronutrient deficiencies in inflammatory bowel disease.
AB - PURPOSE OF REVIEW: Malnutrition, protein-energy, and micronutrient deficiencies
are common among patients with inflammatory bowel disease (IBD). The deficiencies
are a manifestation of the complicated disease and a cause of morbidity. The
present review summarizes recent advances and evidence-based knowledge regarding
micronutrients in relation to patients with IBD. RECENT FINDINGS: Micronutrient
deficiencies occur in more than half of patients with IBD. Most common are
deficiencies of iron, B12, vitamin D, vitamin K, folic acid, selenium, zinc,
vitamin B6, and vitamin B1. Deficiencies are more common in Crohn's disease than
in ulcerative colitis, and more in active disease than at times of remission.
Micronutrient deficiency is associated with prolonged and complicated course of
disease. Iron deficiency is the most common cause for anemia. Definite diagnosis
of B12 deficiency cannot be established by serum levels alone. Vitamin D and
vitamin K deficiencies are thought to be associated with heightened inflammatory
state. The relationship of these deficiencies with bone disease is controversial.
The present review focuses on the significance, epidemiology, treatment options,
and recommendations regarding micronutrient deficiencies in IBD. SUMMARY:
Micronutrient deficiencies are common and have clinical significance. High
suspicion for micronutrient deficiencies is advocated so that treatable causes of
morbidity are treated appropriately and late and irreversible sequlae are
prevented.
PMID- 26418825
TI - Map of Visual Activity in the Infant Brain Sheds Light on Neural Development.
AB - A new study reveals that despite their limited visual acuity, 7-week-old babies
have a surprisingly advanced visual cortex, including the ability to integrate
visual and vestibular motion information. Read the accompanying Research Article.
PMID- 26418824
TI - Osteoporosis and sarcopenia: two diseases or one?
AB - PURPOSE OF REVIEW: This article reviews recently published evidence for common
pathways explaining bone and muscle wasting in normal ageing and pathological
conditions. RECENT FINDINGS: Numerous studies support the concept of a bone
muscle unit, where constant cross-talking between the two tissues takes place,
involving molecules released by the skeletal muscle secretome, which affects
bone, and osteokines secreted by the osteoblasts and osteocytes, which, in turn,
impact muscle cells. SUMMARY: New chemical entities aiming at concomitantly
treating osteoporosis and sarcopenia could be developed by targeting pathways
that centrally regulate bone and muscle or emerging pathways that facilitate the
communication between the two tissues.
PMID- 26418826
TI - Anemia in Chronic Obstructive Pulmonary Disease and the Potential Role of Iron
Deficiency.
AB - The purpose of this review is to evaluate the role of anemia on patient outcomes
in chronic obstructive pulmonary disease (COPD), the potential contribution that
low iron stores may play in this process, and possible treatment considerations.
A review of research studies found that anemia is associated with declining
functional outcomes, increased health care utilization and costs, and increased
mortality in COPD. Associations exist between reduced iron intake and progression
of COPD and in reduction of iron status with declining lung function. Currently
data are limited on the effects of either treating anemia or utilizing iron
supplementation in anemic COPD patients. If iron supplementation might therefore
reverse some of the declines that patients experience, then routine screening and
treatment may turn out to be an effective, simple and inexpensive intervention.
Iron supplementation models utilized in other inflammatory-related disease states
were reviewed as a possible starting point to evaluate treatment options in COPD.
Future research can be directed to establish best practice standards for the use
of iron supplementation in COPD.
PMID- 26418827
TI - Slip of Spreading Viscoplastic Droplets.
AB - The spreading of axisymmetric viscoplastic droplets extruded slowly on glass
surfaces is studied experimentally using shadowgraphy and swept-field confocal
microscopy. The microscopy furnishes vertical profiles of the radial velocity
using particle image velocimetry (PIV) with neutrally buoyant tracers seeded in
the fluid. Experiments were conducted for two complex fluids: aqueous solutions
of Carbopol and xanthan gum. On untreated glass surfaces, PIV demonstrates that
both fluids experience a significant amount of effective slip. The experiments
were repeated on glass that had been treated to feature positive surface charges,
thereby promoting adhesion between the negatively charged polymeric constituents
of the fluids and the glass surface. The Carbopol and xanthan gum droplets spread
more slowly on the treated surface and to a smaller radial distance. PIV
demonstrated that this reduced spreading was associated with a substantial
reduction in slip. For Carbopol, the effective slip could be eliminated entirely
to within the precision of the PIV measurements; the reduction in slip was less
effective for xanthan gum, with a weak slip velocity remaining noticeable.
PMID- 26418828
TI - Engineering the Organophosphorus Acid Anhydrolase Enzyme for Increased Catalytic
Efficiency and Broadened Stereospecificity on Russian VX.
AB - The enzyme organophosphorus acid anhydrolase (OPAA), from Alteromonas sp. JD6.5,
has been shown to rapidly catalyze the hydrolysis of a number of toxic
organophosphorus compounds, including several G-type chemical nerve agents. The
enzyme was cloned into Escherichia coli and can be produced up to approximately
50% of cellular protein. There have been no previous reports of OPAA activity on
VR {Russian VX, O-isobutyl S-[2-(diethylamino)ethyl] methylphosphonothioate}, and
our studies reported here show that wild-type OPAA has poor catalytic efficacy
toward VR. However, via application of a structurally aided protein engineering
approach, significant improvements in catalytic efficiency were realized via
optimization of the small pocket within the OPAA's substrate-binding site. This
optimization involved alterations at only three amino acid sites resulting in a
30-fold increase in catalytic efficiency toward racemic VR, with a strong
stereospecificity toward the P(+) enantiomer. X-ray structures of this mutant as
well as one of its predecessors provide potential structural rationales for their
effect on the OPAA active site. Additionally, a fourth mutation at a site near
the small pocket was found to relax the stereospecificity of the OPAA enzyme.
Thus, it allows the altered enzyme to effectively process both VR enantiomers and
should be a useful genetic background in which to seek further improvements in
OPAA VR activity.
PMID- 26418830
TI - Charge Detection Mass Spectrometry with Almost Perfect Charge Accuracy.
AB - Charge detection mass spectrometry (CDMS) is a single-particle technique where
the masses of individual ions are determined from simultaneous measurement of
each ion's mass-to-charge ratio (m/z) and charge. CDMS has many desirable
features: it has no upper mass limit, no mass discrimination, and it can analyze
complex mixtures. However, the charge is measured directly, and the poor accuracy
of the charge measurement has severely limited the mass resolution achievable
with CDMS. Since the charge is quantized, it needs to be measured with sufficient
accuracy to assign each ion to its correct charge state. This goal has now been
largely achieved. By reducing the pressure to extend the trapping time and by
implementing a novel analysis method that improves the signal-to-noise ratio and
compensates for imperfections in the charge measurement, the uncertainty has been
reduced to less than 0.20 e rmsd (root-mean-square deviation). With this
unprecedented precision peaks due to different charge states are resolved in the
charge spectrum. Further improvement can be achieved by quantizing the charge
(rounding the measured charge to the nearest integer) and culling ions with
measured charges midway between the integral values. After ions with charges more
than one standard deviation from the mean are culled, the fraction of ions
assigned to the wrong charge state is estimated to be 6.4 * 10(-5) (i.e., less
than 1 in 15 000). Since almost all remaining ions are assigned to their correct
charge state, the uncertainty in the mass is now almost entirely limited by the
uncertainty in the m/z measurement.
PMID- 26418829
TI - Effects of particle size and binding affinity for small interfering RNA on the
cellular processing, intestinal permeation and anti-inflammatory efficacy of
polymeric nanoparticles.
AB - BACKGROUND: Silencing of excessive secreted tumour necrosis factor (TNF)-alpha
from macrophages might be an effective therapy of ulcerative colitis (UC), which
acquires improvements on small interfering RNA (siRNA) delivery vectors. Thus, in
the present study, the effects of particle size and binding affinity of four
polymeric nanoparticles on siRNA delivery for the treatment of UC were evaluated.
METHODS: Galactosylated trimethyl chitosan-cysteine (GTC) nanoparticles of
varying particle size and binding affinity for siRNA were prepared and TNF-alpha
siRNA was encapsulated. Their cellular transport was investigated in murine
macrophages and Caco-2 cell monolayers were utilized to analysis the intestinal
permeation. Finally, in vivo anti-inflammatory efficacy was assessed in a mouse
model of UC. RESULTS: Although marginal effects of particle size on the in vitro
gene silencing efficiency were detected, GTC nanoparticles with a particle size
of 450 nm and stronger binding affinity for siRNA showed reduced intestinal
epithelial permeability and enhanced in vivo anti-inflammatory efficacy compared
to those with a particle size of 200 nm. By contrast, the delivery processes were
significantly affected by the binding affinity for siRNA, where smaller GTC
nanoparticles (200 nm) with moderate siRNA binding strength exhibited remarkable
cytoplasmic distribution and sufficient intracellular release of siRNA, as well
as a sustained in vitro and in vivo gene silencing effect. CONCLUSIONS:
Nanoparticles with a particle size of 450 nm or balanced binding affinity for
siRNA might be preferable for the treatment of ulcerative colitis.
PMID- 26418831
TI - Carbon Monoxide-Induced Stability and Atomic Segregation Phenomena in Shape
Selected Octahedral PtNi Nanoparticles.
AB - The chemical and morphological stability of size- and shape-selected octahedral
PtNi nanoparticles (NP) were investigated after different annealing treatments up
to a maximum temperature of 700 degrees C in a vacuum and under 1 bar of CO.
Atomic force microscopy was used to examine the mobility of the NPs and their
stability against coarsening, and X-ray photoelectron spectroscopy to study the
surface composition, chemical state of Pt and Ni in the NPs, and thermally and CO
induced atomic segregation trends. Exposing the samples to 1 bar of CO at room
temperature before annealing in a vacuum was found to be effective at enhancing
the stability of the NPs against coarsening. In contrast, significant coarsening
was observed when the sample was annealed in 1 bar of CO, most likely as a result
of Ni(CO)4 formation and their enhanced mobility on the support surface. Sample
exposure to CO at room temperature prior to annealing led to the segregation of
Pt to the NP surface. Nevertheless, oxidic PtOx and NiOx species still remained
at the NP surface, and, irrespective of the initial sample pretreatment, Ni
surface segregation was observed upon annealing in a vacuum at moderate
temperature (T < 300 degrees C). Interestingly, a distinct atomic segregation
trend was detected between 300 and 500 degrees C for the sample pre-exposed to
CO; namely, Ni surface segregation was partially hindered. This might be
attributed to the higher bonding energy of CO to Pt as compared to Ni. Annealing
in the presence of 1 bar CO also resulted in the initial surface segregation of
Ni (T < 400 degrees C) as long as PtOx and NiOx species were available on the
surface as a result of the higher affinity of Ni for oxygen. Above 500 degrees
C, and regardless of the sample pretreatment, the diffusion of Pt atoms to the NP
surface and the formation of a Ni-Pt alloy are observed.
PMID- 26418832
TI - Early-Onset Vemurafenib-Induced DRESS Syndrome.
AB - Vemurafenib is a BRAF inhibitor indicated in metastatic or unresectable melanoma
in patients with BRAF mutations. Vemurafenib is frequently toxic, but the
toxicity is often not serious. The third case of vemurafenib-induced drug rash
with eosinophilia and systemic symptoms (DRESS) syndrome is reported herein. The
case is unusual in that the onset was early, with symptoms emerging as of day 8
of treatment. Treatment of DRESS syndrome is not currently based on precise
recommendations, but systemic corticosteroid therapy is effective in serious
cases. Severe toxidermias under vemurafenib are exceptional; immediate
discontinuation of treatment upon diagnosis is imperative. Switching from
vemurafenib to dabrafenib then seems to constitute an interesting therapeutic
alternative, since its efficacy is the same but with fewer cutaneous adverse
reactions. This case highlights the importance of awareness of the risk of DRESS
syndrome associated with vemurafenib and monitoring for warning signs from
treatment initiation.
PMID- 26418833
TI - Asbestos exposure and laryngeal cancer mortality.
AB - OBJECTIVES/HYPOTHESIS: Occupational exposure to asbestos occurs in many
workplaces and is well known to cause asbestosis, lung cancer, and mesothelioma.
However, the link between asbestos exposure and other malignancies was not
confirmed. The aim of the current meta-analysis was to provide a summary measure
of risk for laryngeal cancer associated with occupational asbestos exposure.
STUDY DESIGN: Systematic review and meta-analysis. METHODS: Electronic databases
were searched for studies characterizing the association between asbestos and
laryngeal cancer. Standardized mortality rate (SMR) with its 95% confidence
interval (CI) of each study was combined using a fixed or random effect model.
RESULTS: Significantly increased SMR for laryngeal cancer was observed when
subjects were exposed to asbestos (SMR = 1.69, 95% CI = 1.45-1.97, P < .001),
with little evidence of heterogeneity among studies (Q = 15.39, P = .803, I(2) =
0.0%). Effect estimates were larger for cohorts controlling for male subjects,
Europe and Oceania, mining and textile industries, exposure to crocidolite, long
study follow-up (>25 years), and SMR for lung cancer > 2.0. Publication bias was
not detect by Begg test (P = .910) and Egger test (P = .340). CONCLUSIONS: Our
study supports the association of exposure to asbestos with an increased risk of
laryngeal cancer mortality among male workers. LEVEL OF EVIDENCE: NA
Laryngoscope, 126:1169-1174, 2016.
PMID- 26418834
TI - Candida albicans in cystic fibrosis: "Opening statements presented, let the trial
begin".
PMID- 26418835
TI - Strategies for Providing Constructive Feedback to Students.
PMID- 26418836
TI - Authentic Engagement in High-Enrollment Graduate Courses: Pathophysiology
Consumers Become Content Creators.
AB - The challenge to educate increasing numbers of nursing students at all levels in
both online and in-class environments calls for innovative instructional
strategies that may include technology-based assignments to help students apply
knowledge to clinical situations. This article describes a case study assignment
created for a graduate-level pathophysiology course that required students to
create digitally enhanced patient stories. Nursing students enrolled in the
online and in-class sections of the course worked together using commonly
available learning technology tools to create content that bridged
pathophysiology concepts and clinical practice.
PMID- 26418837
TI - Voice Simulation in Nursing Education.
AB - The goal of this study was to improve prelicensure nursing students' attitudes
toward and self-efficacy related to delivering nursing care to patients with
auditory hallucinations. Based on the Hearing Voices That Are Distressing
curriculum, 87 participants were instructed to complete 3 tasks while wearing
headphones delivering distressing voices. Comparing presimulation and
postsimulation results, this study suggests that the simulation significantly
improved attitudes toward patients with auditory hallucinations; however, self
efficacy related to caring for these patients remained largely unchanged.
PMID- 26418838
TI - Prebriefing in Simulation-Based Learning Experiences.
PMID- 26418839
TI - The behavioral characteristics of Sotos syndrome.
AB - In this study we describe the levels of clinically significant behavior in
participants with Sotos syndrome relative to three matched contrast groups in
which the behavioral phenotype is well documented (Autism Spectrum Disorder, ASD;
Prader-Willi, and Down syndromes). Parents and carers of 38 individuals with
Sotos syndrome (mean age = 17.3; SD = 9.36), completed questionnaires regarding
self-injury, aggression, repetitive behavior, autism spectrum phenomenology,
overactivity, impulsivity and mood, interest and pleasure. Individuals with Sotos
syndrome showed an increased risk of self-injurious behavior, physical
aggression, and destruction of property relative to the Down syndrome group but
not a greater risk of stereotyped behavior. Impulsivity and levels of activity
were also significantly higher relative to those with Down syndrome and
comparable to those with ASD. A large proportion of participants met the cut off
score for ASD (70.3%) and Autism (32.4%) on the Social Communication
Questionnaire. Social impairments were particularly prominent with repetitive
behavior and communication impairments less characteristic of the syndrome.
Interestingly, preference for routine and repetitive language were heightened in
individuals with Sotos syndrome and the repetitive behavior profile was
strikingly similar to that observed in individuals with Prader-Willi syndrome.
These findings build upon previous research and provide further evidence of the
behavioral phenotype associated with Sotos syndrome.
PMID- 26418840
TI - Polymorphism in Thermoelectric As2Te3.
AB - Metastable beta-As2Te3 (R3m, a = 4.047 A and c = 29.492 A at 300 K) is
isostructural to layered Bi2Te3 and is known for similarly displaying good
thermoelectric properties around 400 K. Crystallizing glassy-As2Te3 leads to
multiphase samples, while beta-As2Te3 could indeed be synthesized with good phase
purity (97%) by melt quenching. As expected, beta-As2Te3 reconstructively
transforms into stable alpha-As2Te3 (C2/m, a = 14.337 A, b = 4.015 A, c = 9.887
A, and beta = 95.06 degrees ) at 480 K. This beta -> alpha transformation can be
seen as the displacement of part of the As atoms from their As2Te3 layers into
the van der Waals bonding interspace. Upon cooling, beta-As2Te3 displacively
transforms in two steps below T(S1) = 205-210 K and T(S2) = 193-197 K into a new
beta'-As2Te3 allotrope. These reversible and first-order phase transitions give
rise to anomalies in the resistance and in the calorimetry measurements. The new
monoclinic beta'-As2Te3 crystal structure (P2(1)/m, a = 6.982 A, b = 16.187 A, c
= 10.232 A, beta = 103.46 degrees at 20 K) was solved from Rietveld refinements
of X-ray and neutron powder patterns collected at low temperatures. These
analyses showed that the distortion undergone by beta-As2Te3 is accompanied by a
4-fold modulation along its b axis. In agreement with our experimental results,
electronic structure calculations indicate that all three structures are
semiconducting with the alpha-phase being the most stable one and the beta'-phase
being more stable than the beta-phase. These calculations also confirm the
occurrence of a van der Waals interspace between covalently bonded As2Te3 layers
in all three structures.
PMID- 26418841
TI - Six-Year Survival of a Mini Dental Implant-Retained Overdenture in a Child with
Ectodermal Dysplasia.
AB - Patients with ectodermal dysplasia (ED) experience several problems caused by
abnormal development and functioning of the head and neck region. In addition to
developmental nasal cartilage abnormalities and absence of sweat glands, hair,
and eyebrows, edentulism or developmental disorders of teeth (cone-shaped teeth)
are commonly observed in these types of patients. ED is also characterized by
underdeveloped alveolar ridges, a decreased occlusal vertical dimension, reduced
salivary secretion, and dry oral mucosa, which make prosthetic rehabilitation
difficult. Few studies of intraosseous dental implant-retained prostheses have
described adverse effects on craniofacial growth and esthetic and functional
disadvantages, while some researchers have described the advantages of this
treatment option as an alternative option in these cases. Due to the associated
alveolar bone deficiency, dental mini-implant therapy may be a treatment option
for these patients; however, there are isolated cases in the literature regarding
the rehabilitation of ED patients with mini-implant-supported overdentures. This
clinical report describes the rehabilitation of a 6-year-old child with ED using
a maxillary removable partial prosthesis and a mini-implant-retained mandibular
overdenture. The clinical and radiographic findings of this prosthetic
rehabilitation during the 6-year follow-up are also presented.
PMID- 26418842
TI - Further support for the association of GNPAT variant rs11558492 with severe iron
overload in hemochromatosis.
PMID- 26418844
TI - Suitable biopsy site for detection of esophageal eosinophilia in eosinophilic
esophagitis suspected cases.
AB - BACKGROUND AND AIM: Esophageal eosinophilia (EE) is the most important finding
for the diagnosis of eosinophilic esophagitis. We conducted the present
retrospective study to clarify the most suitable site of the esophagus to examine
for EE detection. METHODS: We enrolled 4999 subjects who underwent upper
gastrointestinal endoscopy screening examinations as part of a detailed health
check-up. When endoscopic esophageal abnormalities characteristic of eosinophilic
esophagitis were observed, two or three biopsy specimens were obtained from the
middle or lower esophagus, and endoscopic findings of fixed rings, exudates,
furrows, edema, stricture, and crepe paper esophagus in biopsied sites were
analyzed. RESULTS: Thirty-five subjects underwent histological examination for
EE, of whom 20 showed positive findings in biopsied specimens. Higher grade
endoscopic findings of exudates, furrows, and edema were observed in cases with
EE in comparison to the 15 without EE, whereas statistically significant higher
grade endoscopic findings of exudates, furrows, and edema were also observed in
biopsied sites with EE in comparison to those without EE. In addition, a positive
finding of EE in biopsied specimens from the lower esophagus was significantly
more frequently noted as compared to those from the middle esophagus. Multiple
logistic regression analysis showed that a lower esophagus biopsy site and severe
exudates were significant factors related to a positive EE finding in biopsied
specimens. CONCLUSION: The most suitable conditions for detection of EE are a
lower esophagus biopsy site and the presence of exudates in cases suspicious of
eosinophilic esophagitis shown by endoscopy.
PMID- 26418843
TI - Use of asthma control indicators in measuring inhaled corticosteroid
effectiveness in asthmatic smokers: a systematic review.
AB - OBJECTIVE: The objective of this review is to explore how current research
measures the effectiveness of inhaled corticosteroids (ICS) in smokers with
asthma. DATA SOURCES: PubMed, CINAHL and PsycINFO databases were searched for
combinations of terms relating to asthma, tobacco use and ICS effectiveness.
STUDY SELECTIONS: The search was limited to articles published between 2004 and
2015, in English language. Studies met inclusion criteria if reporting the use of
guideline-based asthma control indicators to measure the therapeutic effects of
ICS or ICS combination therapies. This review did not exclude articles based on
study design. Data were extracted and summarized to describe how indicators were
measured across studies in order to characterize and describe the effects of ICS
in smokers. RESULTS: Thirteen studies were included in this review. Six of these
13 studies used only one indicator to measure asthma control in smokers and ICS
was found to improve asthma in only one of six of these studies. Of studies
evaluating combination therapy, three of four studies reported a therapeutic
benefit to smokers. In these studies of combination therapy multiple indicators
of control were measured to assess drug effects. CONCLUSIONS: To assess the
therapeutic benefit of ICS drugs in smokers, multiple indicators should be
measured to determine if current therapy is improving asthma control. Asthma
therapy should then be adjusted based on the patient's current asthma status. The
development of clinical treatment guidelines for asthmatic smokers may help
clinicians make best-practice, evidence-based recommendations in order to
optimize care for these patients.
PMID- 26418845
TI - What Is the Role of Pyridinium in Pyridine-Catalyzed CO2 Reduction on p-GaP
Photocathodes?
AB - Experimental evidence suggests that pyridinium plays an important role in
photocatalytic CO2 reduction on p-GaP photoelectrodes. Pyridinium reduction to
pyridinyl has been previously proposed as an essential mechanistic step for this
reaction. However, theoretical calculations suggest that this step is not
feasible in solution. Here, cluster models and accurate periodic boundary
condition calculations are used to determine whether such a reduction step could
occur by transfer of photoexcited electrons from the p-GaP photocathode and
whether this transfer could be catalyzed by pyridinium adsorption on the p-GaP
surface. It is found that both the transfer of photoexcited electrons to
pyridinium and pyridinium adsorption are not energetically favored, thus making
very unlikely pyridinium reduction to the pyridinyl radical and the proposed
mechanisms requiring this reduction step. Given this conclusion, an alternative
and energetically viable pathway for pyridinium reduction on p-GaP
photoelectrodes is proposed. This pathway leads to the formation of adsorbed
species that could react to form adsorbed dihydropyridine, which was proposed
previously to play the role of the active catalyst in this system.
PMID- 26418846
TI - Dehydropericyclic Reactions: Symmetry-Controlled Routes to Strained Reactive
Intermediates.
AB - The conceptual dehydrogenation of pericyclic reactions yields dehydropericyclic
processes, which usually lead to strained or reactive intermediates. This is a
simple scheme for inventing new chemical reactions. Computational results on two
novel dehydropericyclic reactions are presented here. Conjugated enynes undergo a
singlet-state photoisomerization that transposes the methylene carbon. We
previously suggested excited-state closure to 1,2-cyclobutadiene followed by
thermal ring opening. CCSD(T)//DFT computations show two minima of similar energy
corresponding to 1,2-cyclobutadiene, one chiral and closed shell and the second a
planar diradical. The chiral structure has a low barrier to ring opening and may
best explain results on enyne photoisomerization. The first examples of 1,3-diyne
+ yne cycloadditions to give o-benzynes were reported in 1997. Computations on
intramolecular versions of this tridehydro (-3H2) Diels-Alder reaction support a
concerted mechanism for the parent triyne (1,3,8-nonatriyne); however, a slight
electronic advantage in the concerted path may be outweighed by the difference in
entropy of activation for sequential vs simultaneous formation of two new ring
bonds.
PMID- 26418847
TI - Health, safety, and environmental management system operation in contracting
companies: A case study.
AB - Systematic and cooperative interactions among parent industry and contractors are
necessary for a successful health, safety, and environmental management system
(HSE-MS). This study was conducted to evaluate the HSE-MS performance in
contracting companies in one of the petrochemical industries in Iran during 2013.
Managers of parent and contracting companies participated in this study. The data
collection forms included 7 elements of an integrated HSE-MS (leadership and
commitment; policy and strategic objectives; organization, resources, and
documentation; evaluation and risk management; planning; implementation and
monitoring; auditing and reviewing). The results showed that mean percentage of
the total scores in seven elements of HSE-MS was 85.7% and 87.0% based on self
report and report of parent company, respectively. In conclusion, this study
showed that HSE-MS was desirably functioning; however, improvement to ensure
health and safety of workers is still required.
PMID- 26418848
TI - Turn-On Ratiometric Fluorescent Probe for Selective Discrimination of Cr(3+) from
Fe(3+) in Aqueous Media for Living Cell Imaging.
AB - Pyrene-based turn-on ratiometric fluorescent probe 1 demonstrates high
sensitivity and exceptional selectivity toward Cr(3+) in the presence of other
metals, including Fe(3+) in aqueous media. Interaction of Cr(3+) with probe 1
brings pyrene moieties close enough to have better aligned pi-pi stacking, thus
enhancing the excimer peak many fold. On the other hand, the interaction of
Fe(3+) with probe 1 brings forth a negligible difference in stacking, resulting
in an insignificant change in fluorescence intensity. Exceptional selectivity of
probe 1 with Cr(3+) over Fe(3+) and other metals has been confirmed by
theoretical studies in addition to experimental results. Imaging of HeLa cells
observed by confocal fluorescence microscopy reveals that probe 1 can be used to
monitor Cr(3+) in live cells to map its subcellular distribution.
PMID- 26418849
TI - Securement of the Indwelling Urinary Catheter: A Prevalence Study.
AB - PURPOSE: The aims of this study were 4-fold: (1) to examine the proportion of
indwelling urinary catheters that were secured in an acute care setting; (2) to
determine the proportion of secured catheters that were secured correctly; (3) to
examine the association of catheter securement with type of unit, age, sex, and
location of insertion; and (4) to determine the proportion of units with catheter
securement products available on the unit. DESIGN: Descriptive prevalence study.
SUBJECTS AND SETTING: All medical and surgical units (n = 21) were surveyed for
inpatients with indwelling urinary catheters in 1 urban tertiary care hospital in
Western Canada. Critical care and pediatric units were excluded. METHODS: During
a 6-hour period, 6 RNs data collectors recorded presence and accuracy of catheter
securement, area where the participant was catheterized, and availability of
securement products on unit. Data were collected using a data form designed for
the study. RESULTS: Seventy-two of 370 inpatients had indwelling catheters on the
day of the study. Of these, 61% (44/72) participated. The overall prevalence of
catheter securement was 18% (8/44). Seven of the 8 secured catheters were secured
correctly. The primary method of securement was a commercial adhesive device
(6/8; 75%). Securement products were stocked on 47% of medicine units and 92% of
surgical units. CONCLUSION: Findings are consistent with other studies and
indicate that catheter securement practices are inadequate despite several
guidelines published on catheter care.
PMID- 26418850
TI - Functional amyloids in bacteria.
AB - The term amyloidosis is used to refer to a family of pathologies altering the
homeostasis of human organs. Despite having a name that alludes to starch
content, the amyloid accumulations are made up of proteins that polymerize as
long and rigid fibers. Amyloid proteins vary widely with respect to their amino
acid sequences but they share similarities in their quaternary structure; the
amyloid fibers are enriched in beta-sheets arranged perpendicular to the axis of
the fiber. This structural feature provides great robustness, remarkable
stability, and insolubility. In addition, amyloid proteins specifically stain
with certain dyes such as Congo red and thioflavin-T. The aggregation into
amyloid fibers, however, it is not restricted to pathogenic processes, rather it
seems to be widely distributed among proteins and polypeptides. Amyloid fibers
are present in insects, fungi and bacteria, and they are important in maintaining
the homeostasis of the organism. Such findings have motivated the use of the term
"functional amyloid" to differentiate these amyloid proteins from their toxic
siblings. This review focuses on systems that have evolved in bacteria that
control the expression and assembly of amyloid proteins on cell surfaces, such
that the robustness of amyloid proteins are used towards a beneficial end.
PMID- 26418851
TI - Cell immobilization of Streptomyces coelicolor : effect on differentiation and
actinorhodin production.
AB - Streptomycetes are mycelium-forming bacteria that produce two thirds of the
clinically relevant secondary metabolites. Despite the fact that secondary
metabolite production is activated at specific developmental stages of the
Streptomyces spp. life cycle, different streptomycetes show different behaviors,
and fermentation conditions need to be optimized for each specific strain and
secondary metabolite. Cell-encapsulation constitutes an interesting alternative
to classical fermentations, which was demonstrated to be useful in Streptomyces,
but development under these conditions remained unexplored. In this work, the
influence of cell-encapsulation in hyphae differentiation and actinorhodin
production was explored in the model Streptomyces coelicolor strain.
Encapsulation led to a delay in growth and to a reduction of mycelium density and
cell death. The high proportion of viable hyphae duplicated extracellular
actinorhodin production in the encapsulated cultures with respect to the non
encapsulated ones.
PMID- 26418852
TI - Phenotypic comparison of clinical and plant-beneficial strains of Pantoea
agglomerans.
AB - Certain strains of Pantoea are used as biocontrol agents for the suppression of
plant diseases. However, their commercial registration is hampered in some
countries because of biosafety concerns. This study compares clinical and plant
beneficial strains of P. agglomerans and related species using a phenotypic
analysis approach in which plant-beneficial effects, adverse effects in nematode
models, and toxicity were evaluated. Plant-beneficial effects were determined as
the inhibition of apple fruit infection by Penicillium expansum and apple flower
infection by Erwinia amylovora. Clinical strains had no general inhibitory
activity against infection by the fungal or bacterial plant pathogens, as only
one clinical strain inhibited P. expansum and three inhibited E. amylovora. By
contrast, all biocontrol strains showed activity against at least one of the
phytopathogens, and three strains were active against both. The adverse effects
in animals were evaluated in the plant-parasitic nematode Meloidogyne javanica
and the bacterial-feeding nematode Caenorhabditis elegans. Both models indicated
adverse effects of the two clinical strains but not of any of the plant
beneficial strains. Toxicity was evaluated by means of hemolytic activity in
blood, and genotoxicity with the Ames test. None of the strains, whether clinical
or plant-beneficial, showed any evidence of toxicity.
PMID- 26418853
TI - A phylogenetic approach to the early evolution of autotrophy: the case of the
reverse TCA and the reductive acetyl-CoA pathways.
AB - In recent decades, a number of hypotheses on the autotrophic origin of life have
been presented. These proposals invoke the emergence of reaction networks leading
from CO or CO2 to the organic molecules required for life. It has also been
suggested that the last (universal) common ancestor (LCA or LUCA) of all extant
cell lineages was a chemolitho-autotrophic thermophilic anaerobe. The antiquity
of some carbon fixation pathways, the phylogenetic basal distribution of some
autotrophic organisms, and the catalytic properties of iron-sulfur minerals have
been advanced in support of these ideas. Here we critically examine the
phylogenetic distribution and evolution of enzymes that are essential for two of
the most ancient autotrophic means of metabolism: the reductive tricarboxylic
acid (rTCA) cycle and the reductive acetyl-CoA pathway. Phylogenetic analysis of
citryl-CoA synthetase and of citryl-CoA lyase, key enzymatic components of the
rTCA cycle, and of CO dehydrogenase/acetyl-CoA synthase, a key enzyme in the
reductive acetyl-CoA pathway, revealed that all three enzymes have undergone
major lateral transfer events and therefore cannot be used as proof of the LCA's
metabolic abilities nor as evidence of an autotrophic origin of life.
PMID- 26418854
TI - Succession of the gut microbiota in the cockroach Blattella germanica.
AB - The cockroach gut harbors a wide variety of microorganisms that, among other
functions, collaborate in digestion and act as a barrier against pathogen
colonization. Blattabacterium, a primary endosymbiont, lives in the fat body
inside bacteriocytes and plays an important role in nitrogen recycling. Little is
known about the mode of acquisition of gut bacteria or their ecological
succession throughout the insect life cycle. Here we report on the bacterial taxa
isolated from different developmental instars of the cockroach Blattella
germanica. The bacterial load in the gut increased two orders of magnitude from
the first to the second nymphal stage, coinciding with the incorporation of the
majority of bacterial taxa, but remained similar thereafter. Pyrosequencing of
the hypervariable regions V1-V3 of the 16S rRNA genes showed that the microbial
composition differed significantly between adults and nymphs. Specifically, a
succession was observed in which Fusobacterium accumulated with aging, while
Bacteroides decreased. Blattabacterium was the only symbiont found in the
ootheca, which makes the vertical transmission of gut bacteria an unlikely mode
of acquisition. Scanning electron microscopy disclosed a rich bacterial biofilm
in third instar nymphs, while filamentous structures were found exclusively in
adults.
PMID- 26418855
TI - A multiplex PCR for the simultaneous detection of Tenacibaculum maritimum and
Edwardsiella tarda in aquaculture.
AB - A specific and sensitive multiplex PCR (mPCR) method was developed as a useful
tool for the simultaneous detection of two important flatfish pathogens in marine
aquaculture, Tenacibaculum maritimum and Edwardsiella tarda. In fish tissues, the
average detection limit for these mPCR-amplified organisms was 2 * 10 5 +/- 0.2
CFU/g and 4 * 10 5 +/- 0.3 CFU/g, respectively. These values are similar or even
lower than those previously obtained using the corresponding single PCR.
Moreover, mPCR did not produce any nonspecific amplification products when tested
against 36 taxonomically related and unrelated strains belonging to 33 different
bacterial species. Large amounts of DNA from one of the target bacterial species
in the presence of low amounts from the other did not have a significant effect
on the amplification sensitivity of the latter.
PMID- 26418856
TI - CDC Report on the Potential Exposure to Anthrax.
AB - The Centers for Disease Control and Prevention (CDC) conducted an internal review
of an incident that involved an unintentional release of potentially viable
anthrax within its Roybal Campus, in Atlanta, Georgia. On June 5, 2014, a
laboratory scientist in the Bioterrorism Rapid Response and Advanced Technology
(BRRAT) laboratory prepared extracts from a panel of eight bacterial select
agents, including Bacillus anthracis (B. anthracis), under biosafety level (BSL)
3 containment conditions. These samples were being prepared for analysis using
matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
spectrometry, a technology that can be used for rapid bacterial species
identification.
PMID- 26418857
TI - Graded Exercise Testing in a Pediatric Weight Management Center: The DeVos
Protocol.
AB - BACKGROUND: In this article, we describe a protocol used to test the functional
capacity of the obese pediatric patient and describe the peak oxygen consumption
(VO2peak) of patients seeking treatment at a pediatric weight management center.
METHODS: One hundred eleven (mean age, 12.5 +/- 3.0 years) patients performed a
multistage exercise test on a treadmill, of which 90 (81%) met end-test criteria
and provided valid VO2peak data. Peak VO2 was expressed: (1) in absolute terms
(L.min(-1)); (2) as the ratio of the volume of oxygen consumed per minute
relative to total body mass (mL.kg(-1).min(-1)); and (3) as the ratio of the
volume of oxygen consumed per minute relative to fat-free mass (mL.FFM.kg(
1).min(-1)). RESULTS: Mean BMI z-score was 2.4 +/- 0.3 and the mean percent body
fat was 36.5 +/- 9.7%. Absolute VO2peak (L.min(-1)) was significantly different
between sexes; however, relative values were similar between sexes. Mean VO2peak
was 25.7 +/- 4.8 mL.kg(-1).min(-1) with a range of 13.5-36.7 mL.kg(-1).min(-1).
CONCLUSIONS: Obese youth seeking treatment at a stage 3 pediatric weight
management center exhibit low VO2peak. The protocol outlined here should serve as
a model for similar programs interested in the submaximal and peak responses to
exercise in obese pediatric patients.
PMID- 26418858
TI - Transformation Pathways of the Recalcitrant Pharmaceutical Compound Carbamazepine
by the White-Rot Fungus Pleurotus ostreatus: Effects of Growth Conditions.
AB - The widely used anticonvulsant pharmaceutical carbamazepine is recalcitrant in
many environmental niches and thus poses a challenge in wastewater treatment. We
followed the decomposition of carbamazepine by the white-rot fungus Pleurotus
ostreatus in liquid culture compared to solid-state fermentation on
lignocellulosic substrate where different enzymatic systems are active.
Carbamazepine metabolites were identified using liquid chromatography-high
resolution mass spectrometry (LC-Q-TOF-MS). In liquid culture, carbamazepine was
only transformed to 10,11-epoxy carbamazepine and 10,11-dihydroxy carbamazepine
as a dead-end product. During solid-state fermentation, carbamazepine metabolism
resulted in the generation of an additional 22 transformation products, some of
which are toxic. Under solid-state-fermentation conditions, 10,11-epoxy
carbamazepine was further metabolized via acridine and 10,11-dihydroxy
carbamazepine pathways. The latter was further metabolized via five subpathways.
When (14)C-carbonyl-labeled carbamazepine was used as the substrate, (14)C-CO2
release amounted to 17.4% of the initial radioactivity after 63 days of
incubation. The proposed pathways were validated using metabolites (10,11-epoxy
carbamazepine, 10,11-dihydroxy carbamazepine, and acridine) as primary substrates
and following their fate at different time points. This work highlights the
effect of growth conditions on the transformation pathways of xenobiotics. A
better understanding of the fate of pollutants during bioremediation treatments
is important for establishment of such technologies.
PMID- 26418859
TI - A Systematic Review of Reporting Tools Applicable to Sexual and Reproductive
Health Programmes: Step 1 in Developing Programme Reporting Standards.
AB - BACKGROUND: Complete and accurate reporting of programme preparation,
implementation and evaluation processes in the field of sexual and reproductive
health (SRH) is essential to understand the impact of SRH programmes, as well as
to guide their replication and scale-up. OBJECTIVES: To provide an overview of
existing reporting tools and identify core items used in programme reporting with
a focus on programme preparation, implementation and evaluation processes.
METHODS: A systematic review was completed for the period 2000-2014. Reporting
guidelines, checklists and tools, irrespective of study design, applicable for
reporting on programmes targeting SRH outcomes, were included. Two independent
reviewers screened the title and abstract of all records. Full texts were
assessed in duplicate, followed by data extraction on the focus, content area,
year of publication, validation and description of reporting items. Data was
synthesized using an iterative thematic approach, where items related to
programme preparation, implementation and evaluation in each tool were extracted
and aggregated into a consolidated list. RESULTS: Out of the 3,656 records
screened for title and abstracts, full texts were retrieved for 182 articles, out
of which 108 were excluded. Seventy-four full text articles corresponding to 45
reporting tools were retained for synthesis. The majority of tools were developed
for reporting on intervention research (n = 15), randomized controlled trials (n
= 8) and systematic reviews (n = 7). We identified a total of 50 reporting items,
across three main domains and corresponding sub-domains: programme preparation
(objective/focus, design, piloting); programme implementation (content,
timing/duration/location, providers/staff, participants, delivery, implementation
outcomes), and programme evaluation (process evaluation, implementation
barriers/facilitators, outcome/impact evaluation). CONCLUSIONS: Over the past
decade a wide range of tools have been developed to improve the reporting of
health research. Development of Programme Reporting Standards (PRS) for SRH can
fill a significant gap in existing reporting tools. This systematic review is the
first step in the development of such standards. In the next steps, we will draft
a preliminary version of the PRS based on the aggregate list of identified items,
and finalize the tool using a consensus process among experts and user-testing.
PMID- 26418860
TI - Association between ST8SIA2 and the Risk of Schizophrenia and Bipolar I Disorder
across Diagnostic Boundaries.
AB - BACKGROUND: Findings from family studies and recent genome-wide association
studies have indicated overlap in the risk genes between schizophrenia and
bipolar disorder (BD). After finding a linkage between the ST8SIA2 (ST8 alpha-N
acetyl-neuraminide alpha-2, 8-sicalyltransferase 2 gene) locus (15q26) and mixed
families with schizophrenia and BD, several studies have reported a significant
association between this gene and schizophrenia or BD. We investigated the
genetic association between ST8SIA2 and both schizophrenia and BD in the Korean
population. METHODS: A total of 582 patients with schizophrenia, 339 patients
with BD, and 502 healthy controls were included. Thirty-one tag single nucleotide
polymorphisms (SNPs) across the ST8SIA2 region and three other SNPs showing
significant associations in previous studies were genotyped. The associations
were evaluated by logistic regression analysis using additive, dominant, and
recessive genetic models. RESULTS: Fourteen of 34 SNPs showed a nominally
significant association (p < 0.05) with at least one diagnostic group. These
association trends were strongest for the schizophrenia and combined
schizophrenia and bipolar I disorder (BD-I) groups. The strongest association was
observed in rs11637898 for schizophrenia (p = 0.0033) and BD-I (p = 0.0050) under
the dominant model. The association between rs11637898 and the combined
schizophrenia and BD-I group (p = 0.0006, under the dominant model) remained
significant after correcting for multiple testing. DISCUSSION: We identified a
possible role of ST8SIA2 in the common susceptibility of schizophrenia and BD-I.
However, no association trend was observed for bipolar II disorder. Further
efforts are needed to identify a specific phenotype associated with this gene
crossing the current diagnostic categories.
PMID- 26418861
TI - The Thiazide-Sensitive Co-Transporter Promotes the Development of Sodium
Retention in Mice with Diet-Induced Obesity.
AB - BACKGROUND/AIMS: Intravascular volume expansion due to sodium retention is
involved in the pathogenesis of obesity-related hypertension. Institution of high
fat diet (HFD) feeding leads to an initial state of positive sodium balance due
to enhanced tubular reabsorption of sodium, but which tubular sodium transporters
are responsible for this remains undefined. METHODS: C57/Bl6 mice were fed
control or HFD for 3 weeks. Blood pressures were recorded by tail cuff method.
Sodium transporter expression and phosphorylation were determined by Western
blotting. In vivo activity of NCC was determined using natriuretic responses to
hydrochlorothiazide. Expression of NCC mRNA was determined using qPCR. RESULTS:
At 3 weeks HFD mice had significant weight gains compared to control mice, but
blood pressures were not yet elevated. There were no changes in expression or
phosphorylation of the bumetanide-sensitive cotransporter, NKCC2, or in
expression of subunits of the amiloride-sensitive ion channel, ENaC. However,
there were significant increases in mRNA and protein expression of the thiazide
sensitive co-transporter, NCC, in kidneys from HFD mice. Consistent with this,
HFD mice had increased in vivo activity of NCC. CONCLUSIONS: Increased expression
of NCC promotes the sodium loading response to institution of HFD feeding before
onset of hypertension.
PMID- 26418863
TI - Stylized Facts in Brazilian Vote Distributions.
AB - Elections, specially in countries such as Brazil, with an electorate of the order
of 100 million people, yield large-scale data-sets embodying valuable information
on the dynamics through which individuals influence each other and make choices.
In this work we perform an extensive analysis of data sets available for
Brazilian proportional elections of legislators and city councilors throughout
the period 1970-2014, which embraces two distinct political regimes: a military
regime followed by a democratic one. We perform a comparative analysis of
elections for legislative positions, in different states and years, through the
distribution p(v) of the number of candidates receiving v votes. We show the
impact of the different political regimes on the vote distributions. Although
p(v) has a common shape, with a scaling behavior, quantitative details change
over time and from one electorate to another. In order to interpret the observed
features, we propose a multi-species model consisting in a system of nonlinear
differential equations, with values of the parameters that reflect the
heterogeneity of candidates. In its simplest setting, the model can not explain
the cutoff, formed by the most voted candidates, whose success is determined
mainly by their peculiar, intrinsic characteristics, such as previous publicity.
However, the modeling allows to interpret the scaling of p(v), yielding a
predictor of the degree of feedback in the interactions of the electorate.
Knowledge of the feedback is relevant beyond the context of elections, since a
similar interactivity may occur for other social contagion processes in the same
population.
PMID- 26418862
TI - Elastography Study of Hamstring Behaviors during Passive Stretching.
AB - INTRODUCTION: The mechanical properties of hamstring muscles are usually inferred
from global passive torque/angle relationships, in combination with adjoining
tissues crossing the joint investigated. Shear modulus measurement provides an
estimate of changes in muscle-tendon stiffness and passive tension. This study
aimed to assess the passive individual behavior of each hamstring muscle in
different stretching positions using shear wave elastography. METHODS/RESULTS:
The muscle shear modulus of each hamstring muscle was measured during a
standardized slow passive knee extension (PKE, 80% of maximal range of motion) on
eighteen healthy male volunteers. Firstly, we assessed the reliability of the
measurements. Results were good for semitendinosus (ST, CV: 8.9%-13.4%),
semimembranosus (SM, CV: 10.3%-11.2%) and biceps femoris long-head (BF-lh, CV:
8.6%-13.3%), but not for biceps femoris short-head (BF-sh, CV: 20.3%-44.9%).
Secondly, we investigated each reliable muscle in three stretch positions: 70
degrees , 90 degrees and 110 degrees of hip flexion. The results showed
different values of shear modulus for the same amount of perceived stretch, with
the highest measurements in the high-flexed hip situation. Moreover, individual
muscles displayed different values, with values increasing or BF-lh, SM and ST,
respectively. The inter-subject variability was 35.3% for ST, 27.4% for SM and
30.2% for BF-lh. CONCLUSION: This study showed that the hip needs to be high
flexed to efficiently tension the hamstrings, and reports a higher muscle-tendon
stress tolerance at 110 degrees of hip angle. In addition muscles have different
passive behaviors, and future works will clarify if it can be linked with rate of
injury.
PMID- 26418864
TI - Sun Protection Behavior in Organ Transplant Recipients in Queensland, Australia.
AB - BACKGROUND: Organ transplant recipients (OTRs) have a high risk of skin cancer,
and excessive sun exposure is a major contributing factor. OBJECTIVE: To document
the prevalence of sun protection and associated factors in OTRs in Queensland,
Australia. METHODS: Cross-sectional study of the frequency of wearing hats, long
sleeves and using sunscreens among OTRs and factors associated with regular use.
Adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) were
estimated using Poisson regression models. RESULTS: Among 446 OTRs, 66, 49 and
39% wore a hat, sunscreen and long sleeves, respectively, mostly when outdoors.
52% regularly practiced multiple sun protection measures while 19% did not.
Sunburn-prone skin (PR = 1.43, 95% CI = 1.06-1.93) and frequent whole-body skin
examinations (PR = 1.48, 95% CI = 1.19-1.84) were independently associated with
regular use of multiple sun protection measures. CONCLUSION: Findings are
consistent with sun-conscious OTRs also having more regular skin screening and
that having frequent skin examinations promotes sun-protective habits.
PMID- 26418865
TI - Multiple breath washout: From Renaissance to Enlightenment?
PMID- 26418866
TI - Value of Information: A Tool to Improve Research Prioritization and Reduce Waste.
AB - In a Guest Editorial, Cosetta Minelli and Gianluca Baio explain how VOI analysis
can prioritize research projects by identifying uncertainty in existing knowledge
and then estimating expected benefits from reducing that uncertainty.
PMID- 26418867
TI - Activated Protein C-Resistance Determination and Vascular Access Thrombosis in
Populations with High Prevalence of Factor V Leiden.
AB - BACKGROUND/AIMS: Factor V Leiden heterozygosity occurs in 3-8% of the general
European and US populations. Activated protein C resistance (APC-R)--a non
molecular laboratory test--can efficiently demonstrate the presence of this
mutation and can be performed on most coagulation analyzers. On the other hand,
fistula or graft thrombosis is a common and costly complication in hemodialysis
patients. Our aim was to establish the value of APC-R determination in
hemodialysis patients by assessing the risk of access thrombosis in patients with
increased APC-R. METHODS: A total of 133 patients (81 men, mean age 64.5 +/- 14.9
years and 52 women, mean age 63.6 +/- 15 years) were selected. Participants were
divided into 2 groups: those with access thrombosis (54 patients, 40.6%) and
those with no access thrombosis (79 patients, 59.4%), and they were tested for
the most common congenital or acquired thrombophilia risk factors. RESULTS:
Overall, 12 patients (9%) had an increased APC-R and 10 of them had at least 1
episode of access thrombosis (83.3%). Univariate analysis to estimate crude odds
ratio (OR) showed an OR of 8.8 (95% CI 1.8-41.8) times higher risk for access
thrombosis in these patients. No significant differences were found after
adjusting for age, hypertension, diabetes mellitus, coronary artery disease,
cerebrovascular disease, peripheral arterial disease and malignancy. Sex was also
a factor influencing thrombosis, presenting a higher OR for women (OR 2.2, 95% CI
1.1-4.4). CONCLUSION: This study revealed a significant association between
access thrombosis and increased APC-R in hemodialysis patients. This indicates
that the determination of APC-R should be considered--especially, in populations
with a high prevalence of Factor V Leiden--as proper anticoagulant therapy in
these patients may reduce the risk of access thrombosis.
PMID- 26418868
TI - Impact of McKenzie Method Therapy Enriched by Muscular Energy Techniques on
Subjective and Objective Parameters Related to Spine Function in Patients with
Chronic Low Back Pain.
AB - BACKGROUND: The high incidence and inconsistencies in diagnostic and therapeutic
process of low back pain (LBP) stimulate the continuing search for more efficient
treatment modalities. Integration of the information obtained with various
therapeutic methods and a holistic approach to the patient seem to be associated
with positive outcomes. The aim of this study was to analyze the efficacy of
combined treatment with McKenzie method and Muscle Energy Technique (MET), and to
compare it with the outcomes of treatment with McKenzie method or standard
physiotherapy in specific chronic lumbar pain. MATERIAL AND METHODS: The study
included 60 men and women with LBP (mean age 44 years). The patients were
randomly assigned to 1 of 3 therapeutic groups, which were further treated with:
1) McKenzie method and MET, 2) McKenzie method alone, or 3) standard
physiotherapy for 10 days. The extent of spinal movements (electrogoniometry),
level of experienced pain (Visual Analogue Scale and Revised Oswestry Pain
Questionnaire), and structure of the spinal discs (MRI) were examined prior to
the intervention, immediately thereafter, and 3 months after the intervention.
RESULTS: McKenzie method enriched with MET had the best therapeutic outcomes. The
mobility of cervical, thoracic, and lumbar spine normalized at levels
corresponding to 87.1%, 66.7%, and 95% of respective average normative values.
Implementation of McKenzie method, both alone and combined with MET, was
associated with a significant decrease in Oswestry Disability Index, significant
alleviation of pain (VAS), and significantly reduced size of spinal disc
herniation. CONCLUSIONS: The combined method can be effectively used in the
treatment of chronic LBP.
PMID- 26418869
TI - Ex-Situ Kinetic Investigations of the Formation of the Poly-Oxo Cluster U38.
AB - The ex-situ qualitative study of the kinetic formation of the poly-oxo cluster
U38 , has been investigated after the solvothermal reaction. The resulting
products have been characterized by means of powder XRD and scanning electron
microscopy (SEM) for the solid phase and UV/Vis, X-ray absorption near edge
structure (XANES), extended X-ray absorption fine structure (EXAFS), and NMR
spectroscopies for the supernatant liquid phase. The analysis of the different
synthesis batches, stopped at different reaction times, revealed the formation of
spherical crystallites of UO2 from t=3 h, after the formation of unknown solid
phases at an early stage. The crystallization of U38 occurred from t=4 h at the
expense of UO2 , and is completed after t=8 h. Starting from pure uranium(IV)
species in solution (t=0-1 h), oxidation reactions are observed with a U(IV)
/U(VI) ratio of 70:30 for t=1-3 h. Then, the ratio is inversed with a U(IV)
/U(VI) ratio of 25/75, when the precipitation of UO2 occurs. Thorough SEM
observations of the U38 crystallites showed that the UO2 aggregates are embedded
within. This may indicate that UO2 acts as reservoir of uranium(IV), for the
formation of U38 , stabilized by benzoate and THF ligands. During the early
stages of the U38 crystallization, a transient crystallized phase appeared at t=4
h. Its crystal structure revealed a new dodecanuclear moiety (U12 ), based on the
inner hexanuclear core of {U6 O8 } type, decorated by three additional pairs of
dinuclear U2 units. The U12 motif is stabilized by benzoate, oxalates, and
glycolate ligands.
PMID- 26418870
TI - Technique, Results, and Complications Related to Robot-Assisted
Stereoelectroencephalography.
AB - BACKGROUND: Robot-assisted stereoelectroencephalography (SEEG) may represent a
simplified, precise, and safe alternative to the more traditional SEEG
techniques. OBJECTIVE: To report our clinical experience with robotic SEEG
implantation and to define its utility in the management of patients with
medically refractory epilepsy. METHODS: The prospective observational analyses
included all patients with medically refractory focal epilepsy who underwent
robot-assisted stereotactic placement of depth electrodes for extraoperative
brain monitoring between November 2009 and May 2013. Technical nuances of the
robotic implantation technique are presented, as well as an analysis of
demographics, time of planning and procedure, seizure outcome, in vivo accuracy,
and procedure-related complications. RESULTS: One hundred patients underwent 101
robot-assisted SEEG procedures. Their mean age was 33.2 years. In total, 1245
depth electrodes were implanted. On average, 12.5 electrodes were implanted per
patient. The time of implantation planning was 30 minutes on average (range, 15
60 minutes). The average operative time was 130 minutes (range, 45-160 minutes).
In vivo accuracy (calculated in 500 trajectories) demonstrated a median entry
point error of 1.2 mm (interquartile range, 0.78-1.83 mm) and a median target
point error of 1.7 mm (interquartile range, 1.20-2.30 mm). Of the group of
patients who underwent resective surgery (68 patients), 45 (66.2%) gained seizure
freedom status. Mean follow-up was 18 months. The total complication rate was 4%.
CONCLUSION: The robotic SEEG technique and method were demonstrated to be safe,
accurate, and efficient in anatomically defining the epileptogenic zone and
subsequently promoting sustained seizure freedom status in patients with
difficult-to-localize seizures.
PMID- 26418873
TI - In Reply: A Survey of Chronic Pain Due to Spinal Dural Arteriovenous Fistulae.
PMID- 26418875
TI - Commentary: Endoscopic Third Ventriculostomy in 250 Adults With Hydrocephalus:
Patient Selection, Outcomes, and Complications.
PMID- 26418876
TI - Imaging of carbonic anhydrase IX with an 111In-labeled dual-motif inhibitor.
AB - We developed a new scaffold for radionuclide-based imaging and therapy of clear
cell renal cell carcinoma (ccRCC) targeting carbonic anhydrase IX (CAIX).
Compound XYIMSR-01, a DOTA-conjugated, bivalent, low-molecular-weight ligand, has
two moieties that target two separate sites on CAIX, imparting high affinity. We
synthesized [111In]XYIMSR-01 in 73.8-75.8% (n = 3) yield with specific
radioactivities ranging from 118 - 1,021 GBq/MUmol (3,200-27,600 Ci/mmol). Single
photon emission computed tomography of [111In]XYIMSR-01 in immunocompromised mice
bearing CAIX-expressing SK-RC-52 tumors revealed radiotracer uptake in tumor as
early as 1 h post-injection. Biodistribution studies demonstrated 26% injected
dose per gram of radioactivity within tumor at 1 h. Tumor-to-blood, muscle and
kidney ratios were 178.1 +/- 145.4, 68.4 +/- 29.0 and 1.7 +/- 1.2, respectively,
at 24 h post-injection. Retention of radioactivity was exclusively observed in
tumors by 48 h, the latest time point evaluated. The dual targeting strategy to
engage CAIX enabled specific detection of ccRCC in this xenograft model, with
pharmacokinetics surpassing those of previously described radionuclide-based
probes against CAIX.
PMID- 26418877
TI - The Vacuolar ATPase a2-subunit regulates Notch signaling in triple-negative
breast cancer cells.
AB - Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer with poor
prognosis for which no targeted therapies are currently available. Notch
signaling has been implicated in breast cancer but the factors that control Notch
in TNBC are unknown. Because the Vacuolar ATPase has been shown to be important
in breast cancer invasiveness, we investigated the role of a2-subunit isoform of
Vacuolar ATPase (a2V) in regulating Notch signaling in TNBC. Confocal microscopy
revealed that among all the 'a' subunit isoforms, a2V was uniquely expressed on
the plasma membrane of breast cancer cells. Both a2V and NOTCH1 were elevated in
TNBC tumors tissues and cell lines. a2V knockdown by siRNA as well as V-ATPase
inhibition by Bafilomycin A1 (Baf A1) in TNBC cell lines enhanced Notch signaling
by increasing the expression of Notch1 intracellular Domain (N1ICD). V-ATPase
inhibition blocked NICD degradation by disrupting autophagy and lysosomal
acidification as demonstrated by accumulation of LC3B and diminished expression
of LAMP1 respectively. Importantly, treatment with Baf A1 or anti-a2V, a novel
neutralizing antibody against a2V hindered cell migration of TNBC cells. Our
findings indicate that a2V regulates Notch signaling through its role in
endolysosomal acidification and emerges as a potential target for TNBC.
PMID- 26418879
TI - TTK activates Akt and promotes proliferation and migration of hepatocellular
carcinoma cells.
AB - Hepatocellular carcinoma (HCC) is one of the most malignant cancers with poor
clinical outcome. The protein kinase human monopolar spindle 1 (hMps1/TTK) gene
expression is significantly increased in HCCs. However, its contributions to
hepatocarcinogenesis remain unclear. In this study, we found that TTK was
overexpressed in 77.63% (118/152) HCC specimens. Elevated TTK expression
positively correlated with large tumor size and presence of the portal vein tumor
thrombus (PVTT). Demethylation in its promoter increased TTK expression in HCC.
In vitro assays revealed that TTK not only promoted cell proliferation and
anchorage-independent growth, but also cell migration. Subsequent investigations
revealed that TTK activated Akt/mTOR pathway in a p53 dependent manner. We also
found that TTK specific kinase inhibitor AZ3146 could decrease HCC cell growth.
In conclusion, TTK contributes to HCC tumorigenesis via promoting cell
proliferation and migration. It may serve as a novel biomarker and a potential
target in HCC cancer therapy.
PMID- 26418878
TI - The metastasis suppressor, NDRG1, inhibits "stemness" of colorectal cancer via
down-regulation of nuclear beta-catenin and CD44.
AB - N-myc downstream-regulated gene 1 (NDRG1), has been identified as an important
metastasis suppressor for colorectal cancer (CRC). In this study, we
investigated: (1) the effects of NDRG1 on CRC stemness and tumorigenesis; (2) the
molecular mechanisms involved; and (3) the relationship between NDRG1 expression
and colorectal cancer prognosis. Our investigation demonstrated that CRC cells
with silenced NDRG1 showed more tumorigenic ability and stem cell-like
properties, such as: colony and sphere formation, chemoresistance, cell invasion,
high expression of CD44, and tumorigenicity in vivo. Moreover, NDRG1 silencing
reduced beta-catenin expression on the cell membrane, while increasing its
nuclear expression. The anti-tumor activity of NDRG1 was demonstrated to be
mediated by preventing beta-catenin nuclear translocation, as silencing of this
latter molecule could reverse the effects of silencing NDRG1 expression. NDRG1
expression was also demonstrated to be negatively correlated to CRC prognosis. In
addition, there was a negative correlation between NDRG1 and nuclear beta-catenin
and also NDRG1 and CD44 expression in clinical CRC specimens. Taken together, our
investigation demonstrates that the anti-metastatic activity of NDRG1 in CRC
occurs through the down-regulation of nuclear beta-catenin and suggests that
NDRG1 is a significant therapeutic target.
PMID- 26418880
TI - Suppressor of Ty homolog-5, a novel tumor-specific human telomerase reverse
transcriptase promoter-binding protein and activator in colon cancer cells.
AB - The human telomerase reverse transcriptase (hTERT) promoter promotes differential
hTERT gene expression in tumor cells and normal cells. However, information on
the mechanisms underlying the differential hTERT transcription and induction of
telomerase activity in tumor cells is limited. In the present study, suppressor
of Ty homolog-5 (SPT5), a protein encoded by the SUPT5H gene, was identified as a
novel tumor-specific hTERT promoter-binding protein and activator in colon cancer
cells. We verified the tumor-specific binding activity of SPT5 to the hTERT
promoter in vitro and in vivo and detected high expression levels of SUPT5H in
colorectal cancer cell lines and primary human colorectal cancer tissues. SUPT5H
was more highly expressed in colorectal cancer cases with distant metastasis than
in cases without distant metastasis. Inhibition of endogenous SUPT5H expression
by SUPT5H gene-specific short hairpin RNAs effectively attenuated hTERT promoter
driven green fluorescent protein (GFP) expression, whereas no detectable effects
on CMV promoter-driven GFP expression in the same cells were observed. In
addition, inhibition of SUPT5H expression not only effectively repressed
telomerase activity, accelerated telomere shortening, and promoted cell
senescence in colon cancer cells, but also suppressed cancer cell growth and
migration. Our results demonstrated that SPT5 contributes to the up-regulation of
hTERT expression and tumor development, and SUPT5H may potentially be used as a
novel tumor biomarker and/or cancer therapeutic target.
PMID- 26418881
TI - The effective bioengineering method of implantation decellularized renal
extracellular matrix scaffolds.
AB - End stage renal disease (ESRD) is a progressive loss of kidney function with a
high rate of morbidity and mortality. Transplantable organs are hard to come by
and hold a high risk of recipient immune rejection. We intended to establish a
more effective and faster method to decellularize and recellularize the kidney
scaffold for transplant and regeneration. We successfully produced renal
scaffolds by decellularizing rat kidneys with 0.5% sodium dodecyl sulfate (SDS),
while still preserving the extracellular matrix (ECM) 3D architecture, an intact
vascular tree and biochemical components. We recellularized the kidney scaffolds
with mouse embryonic stem (ES) cells that then populated and proliferated within
the glomerular, vascular, and tubular structures. After in vivo implantation,
these recellularized scaffolds were easily reperfused, tolerated blood pressure
and produced urine with no blood leakage. Our methods can successfully
decellularize and recellularize rat kidneys to produce functional renal ECM
scaffolds. These scaffolds maintain their basic components, retain intact
vasculature and show promise for kidney regeneration.
PMID- 26418882
TI - Biomarkers of Brain Structure and Function for Neurodegenerative Disorders: Are
They Adequate for Go/No Go Decisions in Drug Development?
AB - Given the high risk of developing drugs for neurodegenerative diseases if post
phase I decisions to go into efficacy studies were made with quantitative
knowledge of an agent's action in brain, the risks should be diminished.
Furthermore, if biomarkers were compelling, they could be utilized during a
lengthy trial as an early measure of futility. What follows is one perspective on
the adequacy of current and emerging measures to be applied to such decision
making.
PMID- 26418883
TI - Strains Around Abutment Teeth with Different Attachments Used for Implant
Assisted Distal Extension Partial Overdentures: An In Vitro Study.
AB - PURPOSE: The aim of this study was to evaluate and compare strain around abutment
teeth with different attachments used for implant-assisted distal extension
partial overdentures (IADEPODs). MATERIALS AND METHODS: A mandibular Kennedy
class I acrylic model (remaining teeth from first premolar to first premolar) was
constructed. A conventional partial denture was constructed over the model
(control, group 1). Two laboratory implants were then placed bilaterally in the
first molar areas parallel to each other and perpendicular to the residual ridge.
Three additional experimental partial overdentures (PODs) were constructed and
connected to the implants using ball (group 2), magnetic (group 3), and Locator
(group 4) attachments. Three linear strain gauges were bonded buccal, lingual,
and distal to the first premolar abutment tooth at the right (loading) and the
left (nonloading) sides. For each group, a universal testing device was used to
apply a unilateral vertical static load (50 N) on the first molar area, and the
strain was recorded using a multichannel digital strainometer. RESULTS:
Significant differences between groups and between sites of strain gauges were
detected. Strains recorded for all groups were compressive (negative) in nature.
Group 1 demonstrated the highest strain, followed by group 3 and group 4; group 2
recorded the lowest strain. For group 2, the highest strain was recoded at the
lingual nonloading side. For group 1, group 3, and group 4, the highest strain
was recorded at the buccal loading side. CONCLUSION: Within the limitation of the
present study, ball attachments used to retain IADEPODs to the implants were
associated with lower strains around abutment teeth than Locator and magnetic
attachments. The highest strain was recorded with conventional partial dentures.
PMID- 26418884
TI - Serological Evidence of Infection by Leishmania (Leishmania) infantum (Synonym:
Leishmania (Leishmania) chagasi) in Free-Ranging Wild Mammals in a Nonendemic
Region of the State of Sao Paulo, Brazil.
AB - Concerns about the interface between wildlife, domestic animals, and humans in
the transmission of visceral leishmaniasis (VL) have been growing due to natural
or anthropogenic environmental changes. In this context, investigations of the
infection in wild mammals are important to assess their exposure to the vector
and the parasite. A study of anti-Leishmania (Leishmania) infantum antibodies was
carried out using the direct agglutination test (DAT) on 528 free-ranging wild
mammals of 38 species from the region of Botucatu, state of Sao Paulo, Brazil, a
municipality that has no records of the vector or of human or canine autochthony.
Antibodies were detected, with a cutoff of 1:320, in 9/528 (1.7%; 95% confidence
interval [CI] 0.6-2.8%) mammals of the species Callithrix jacchus, Lepus
europaeus, Sphiggurus villosus, Nasua nasua, Eira barbara, and Galictis cuja,
with high titers (>=1280) for the last three. These three are little-studied
species, and previous records of the detection of anti-Leishmania spp. antibodies
in Brazil exist only for coatis (N. nasua), whereas worldwide, infection by L.
(L.) infantum has been confirmed only in hares (Le. europaeus). On the other
hand, opossums and canids, the species most commonly reported to be naturally
infected by L. (L.) infantum, were not seropositive. Fifty-eight (58/528; 10.9%)
mammals were found to have antibody titers ranging from 20 to 160 and were not
included among the seropositive animals due to the adopted cutoff. However, the
possibility of infection in these animals should not be discarded, because there
is no standard cutoff point for the different wild species. Our findings indicate
the need for investigations into the exact role of the seropositive species in
the epidemiology of VL and for effective epidemiological surveillance to prevent
its expansion, because even in regions where there are no records of canine or
human autochthonous cases, there may be parasite circulation among wild mammals.
PMID- 26418885
TI - Assessment of ICD-9-based case definitions for influenza-like illness
surveillance.
AB - Population-based surveillance of influenza routinely relies on administrative
medical encounter databases and ICD-9 codes. However, an assessment of the ICD-9
codes used for the Department of Defense (DoD) influenza-like illness (ILI) case
definition has not been conducted since 2007. As coding practices may have
changed over time, this analysis was done to determine the sensitivity,
specificity, and positive predictive value (PPV) of the current ILI case
definition and three alternative case definitions for the 2014-2015 influenza
season. Influenza laboratory tests conducted on specimens from DoD beneficiaries
during the 2014-2015 season were matched to ambulatory and inpatient medical
encounters. The current DoD ILI case definition had high sensitivity (92%) but
low specificity (30%) and moderate PPV (63%). A more specific ILI case definition
utilizing only codes with greater than 75% influenza positivity for the matched
laboratory test had high specificity (96%) and PPV (96%) and moderate sensitivity
(62%). The current ILI case definition is sufficient for broad, sensitive
population-based surveillance; however, an alternative case definition may be
more appropriate when there is a need to maximize specificity.
PMID- 26418886
TI - Incidence of syphilis, active component, U.S. Armed Forces, 1 January 2010
through 31 August 2015.
AB - In 2014,the Centers for Disease Control and Prevention reported significant
increases in cases of primary and secondary syphilis in the U.S.; among
beneficiaries of the Military Health System, monthly surveillance reports
tracking reportable medical events of syphilis have reflected similar increases.
This analysis reports on incident cases and rates of syphilis among active
component service members of the U.S. Armed Forces from 1 January 2010 through 31
August 2015. During the surveillance period, 2,976 cases of syphilis were
diagnosed. Crude incidence rates increased from 30.9 cases per 100,000 person
years (p-yrs) in 2010 to 47.4 cases per 100,000 p-yrs in 2015. Males accounted
for 88.7% of cases. Incidence rates of syphilis were highest among service
members who were black, non-Hispanic or who were aged 20-29 years. About one
quarter of syphilis cases (24.4%; 727 cases) were diagnosed as HIV infected.
Primary and secondary syphilis cases comprised 42% of all syphilis cases.
Increasing rates of primary and secondary syphilis in active component service
members reflect similar trends reported in the U.S. civilian population.
PMID- 26418887
TI - Brief report: Rate of prescriptions by therapeutic classification, active
component, U.S. Armed Forces, 2014.
PMID- 26418888
TI - Bayesian spatiotemporal analysis of zero-inflated biological population density
data by a delta-normal spatiotemporal additive model.
AB - We evaluate the spatiotemporal changes in the density of a particular species of
crustacean known as deep-water rose shrimp, Parapenaeus longirostris, based on
biological sample data collected during trawl surveys carried out from 1995 to
2006 as part of the international project MEDITS (MEDiterranean International
Trawl Surveys). As is the case for many biological variables, density data are
continuous and characterized by unusually large amounts of zeros, accompanied by
a skewed distribution of the remaining values. Here we analyze the normalized
density data by a Bayesian delta-normal semiparametric additive model including
the effects of covariates, using penalized regression with low-rank thin-plate
splines for nonlinear spatial and temporal effects. Modeling the zero and nonzero
values by two joint processes, as we propose in this work, allows to obtain great
flexibility and easily handling of complex likelihood functions, avoiding
inaccurate statistical inferences due to misclassification of the high proportion
of exact zeros in the model. Bayesian model estimation is obtained by Markov
chain Monte Carlo simulations, suitably specifying the complex likelihood
function of the zero-inflated density data. The study highlights relevant
nonlinear spatial and temporal effects and the influence of the annual
Mediterranean oscillations index and of the sea surface temperature on the
distribution of the deep-water rose shrimp density.
PMID- 26418889
TI - Cationic Cobalt(III)-Catalyzed Aryl and Alkenyl C-H Amidation: A Mild Protocol
for the Modification of Purine Derivatives.
AB - A cationic cobalt(III)-catalyzed direct C-H amidation of unactivated
(hetero)arenes and alkenes by using 1,4,2-dioxazol-5-ones as the amidating
reagent has been developed. This transformation proceeds efficiently under
external oxidant-free conditions with a broad substrate scope. Moreover, 6
arylpurine compounds, which often exhibit high potency in antimycobacterial,
cytostatic, and anti-HCV activities, can be smoothly amidated, thus offering a
mild protocol for their late stage functionalization.
PMID- 26418891
TI - N-Acyl Amino Acid Ligands for Ruthenium(II)-Catalyzed meta-C-H tert-Alkylation
with Removable Auxiliaries.
AB - Acylated amino acid ligands enabled ruthenium(II)-catalyzed C-H
functionalizations with excellent levels of meta-selectivity. The outstanding
catalytic activity of the ruthenium(II) complexes derived from monoprotected
amino acids (MPAA) set the stage for the first ruthenium-catalyzed meta
functionalizations with removable directing groups. Thereby, meta-alkylated
anilines could be accessed, which are difficult to prepare by other means of
direct aniline functionalizations. The robust nature of the versatile
ruthenium(II)-MPAA was reflected by challenging remote C-H transformations with
tertiary alkyl halides on aniline derivatives as well as on pyridyl-, pyrimidyl-,
and pyrazolyl-substituted arenes. Detailed mechanistic studies provided strong
support for an initial reversible C-H ruthenation, followed by a SET-type C-Hal
activation through homolytic bond cleavage. Kinetic analyses confirmed this
hypothesis through an unusual second-order dependence of the reaction rate on the
ruthenium catalyst concentration. Overall, this report highlights the exceptional
catalytic activity of ruthenium complexes derived from acylated amino acids,
which should prove instrumental for C-H activation chemistry beyond remote
functionalization.
PMID- 26418890
TI - Probing Structural Dynamics and Topology of the KCNE1 Membrane Protein in Lipid
Bilayers via Site-Directed Spin Labeling and Electron Paramagnetic Resonance
Spectroscopy.
AB - KCNE1 is a single transmembrane protein that modulates the function of voltage
gated potassium channels, including KCNQ1. Hereditary mutations in the genes
encoding either protein can result in diseases such as congenital deafness, long
QT syndrome, ventricular tachyarrhythmia, syncope, and sudden cardiac death.
Despite the biological significance of KCNE1, the structure and dynamic
properties of its physiologically relevant native membrane-bound state are not
fully understood. In this study, the structural dynamics and topology of KCNE1 in
bilayered lipid vesicles was investigated using site-directed spin labeling
(SDSL) and electron paramagnetic resonance (EPR) spectroscopy. A 53-residue
nitroxide EPR scan of the KCNE1 protein sequence including all 27 residues of the
transmembrane domain (45-71) and 26 residues of the N- and C-termini of KCNE1 in
lipid bilayered vesicles was analyzed in terms of nitroxide side-chain motion.
Continuous wave-EPR spectral line shape analysis indicated the nitroxide spin
label side-chains located in the KCNE1 TMD are less mobile when compared to the
extracellular region of KCNE1. The EPR data also revealed that the C-terminus of
KCNE1 is more mobile when compared to the N-terminus. EPR power saturation
experiments were performed on 41 sites including 18 residues previously proposed
to reside in the transmembrane domain (TMD) and 23 residues of the N- and C
termini to determine the topology of KCNE1 with respect to the 1-palmitoyl-2
oleoyl-sn-glycero-3-phosphocholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3
phospho-(1'-rac-glycerol) (POPG) lipid bilayers. The results indicated that the
transmembrane domain is indeed buried within the membrane, spanning the width of
the lipid bilayer. Power saturation data also revealed that the extracellular
region of KCNE1 is solvent-exposed with some of the portions partially or weakly
interacting with the membrane surface. These results are consistent with the
previously published solution NMR structure of KCNE1 in micelles.
PMID- 26418892
TI - Effectiveness of Influenza Vaccination for Individuals with Chronic Obstructive
Pulmonary Disease (COPD) in Low- and Middle-Income Countries.
AB - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of
death globally. In addition to the mortality associated with it, people with COPD
experience significant morbidity, making this set of conditions a major public
health concern. Infections caused by influenza virus are a preventable cause of
morbidity and vaccination has been shown to be effective. The evidence of their
benefit in persons with COPD mainly comes from high-income countries where
influenza vaccination is used in routine practice, but little is known about the
effectiveness, cost-effectiveness, and scalability of vaccination in low- and
middle-income countries. We therefore systematically reviewed and present
evidence related to vaccination against influenza in persons with COPD with a
special focus on studies from low- and middle-income countries (LMICs). Available
data from 19 studies suggest that the use of influenza vaccine in persons with
COPD is beneficial, cost-effective, and may be relevant for low- and middle
income countries. Wider implementation of this intervention needs to take into
account the health care delivery systems of LMICs and use of prevalent viral
strains in vaccines to be most cost effective.
PMID- 26418894
TI - Interpenetration of a 3D Icosahedral M@Ni12 (M=Al, Ga) Framework with Porphyrin
Reminiscent Boron Layers in MNi9 B8.
AB - Two ternary borides MNi9 B8 (M=Al, Ga) were synthesized by thermal treatment of
mixtures of the elements. Single-crystal X-ray diffraction data reveal AlNi9 B8
and GaNi9 B8 crystallizing in a new type of structure within the space group Cmcm
and the lattice parameters a=7.0896(3) A, b=8.1181(3) A, c=10.6497(4) A and
a=7.0897(5) A, b=8.1579(4) A, c=10.6648(7) A, respectively. The boron atoms build
up two-dimensional layers, which consist of puckered [B16 ] rings with two
tailing B atoms, whereas the M atoms reside in distorted vertices-condensed [Ni12
] icosahedra, which form a three-dimensional framework interpenetrated by boron
porphyrin-reminiscent layers. An unusual local arrangement resembling a giant
metallo-porphyrin entity is formed by the [B16 ] rings, which, due to their large
annular size of approximately 8 A, chelate four of the twelve icosahedral Ni
atoms. An analysis of the chemical bonding by means of the electron
localizability approach reveals strong covalent B-B interactions and weak Ni-Ni
interactions. Multi-center dative B-Ni interaction occurs between the Al-Ni
framework and the boron layers. In agreement with the chemical bonding analysis
and band structure calculations, AlNi9 B8 is a Pauli-paramagnetic metal.
PMID- 26418893
TI - Definitive Hematopoiesis in the Yolk Sac Emerges from Wnt-Responsive Hemogenic
Endothelium Independently of Circulation and Arterial Identity.
AB - Adult-repopulating hematopoietic stem cells (HSCs) emerge in low numbers in the
midgestation mouse embryo from a subset of arterial endothelium, through an
endothelial-to-hematopoietic transition. HSC-producing arterial hemogenic
endothelium relies on the establishment of embryonic blood flow and arterial
identity, and requires beta-catenin signaling. Specified prior to and during the
formation of these initial HSCs are thousands of yolk sac-derived erythro-myeloid
progenitors (EMPs). EMPs ensure embryonic survival prior to the establishment of
a permanent hematopoietic system, and provide subsets of long-lived tissue
macrophages. While an endothelial origin for these HSC-independent definitive
progenitors is also accepted, the spatial location and temporal output of yolk
sac hemogenic endothelium over developmental time remain undefined. We performed
a spatiotemporal analysis of EMP emergence, and document the morphological steps
of the endothelial-to-hematopoietic transition. Emergence of rounded EMPs from
polygonal clusters of Kit(+) cells initiates prior to the establishment of
arborized arterial and venous vasculature in the yolk sac. Interestingly, Kit(+)
polygonal clusters are detected in both arterial and venous vessels after
remodeling. To determine whether there are similar mechanisms regulating the
specification of EMPs with other angiogenic signals regulating adult-repopulating
HSCs, we investigated the role of embryonic blood flow and Wnt/beta-catenin
signaling during EMP emergence. In embryos lacking a functional circulation,
rounded Kit(+) EMPs still fully emerge from unremodeled yolk sac vasculature. In
contrast, canonical Wnt signaling appears to be a common mechanism regulating
hematopoietic emergence from hemogenic endothelium. These data illustrate the
heterogeneity in hematopoietic output and spatiotemporal regulation of primary
embryonic hemogenic endothelium.
PMID- 26418895
TI - The efficacy and safety of Endostar combined with chemoradiotherapy for patients
with advanced, locally recurrent nasopharyngeal carcinoma.
AB - PURPOSE: To evaluate the short-term efficacy and safety of recombinant human
endostatin (Endostar) combined with chemoradiotherapy for the treatment of
advanced, locally recurrent nasopharyngeal carcinoma (NPC). MATERIALS AND
METHODS: Between March 2010 and October 2013, a total of 22 patients with stage
rIII-IVb locally recurrent NPC underwent salvage radiotherapy with Endostar in
Sun Yat-Sen University Cancer Center. Intensity-modulated radiotherapy (IMRT) was
delivered. Platinum-based chemotherapy was used in a neoadjuvant protocol.
Endostar was continuously administered intravenously (105 mg/m2) for 14 days
(Days 1-14) from the first day of treatment during a 21-day cycle. Tumor response
and treatment toxicities were observed. RESULTS: Until January 2014, the median
follow-up time was 13 months (range, 4-41 months). All patients completed the
planned radiotherapy. A complete response was achieved in 20 patients, and a
partial response was achieved in 2 patients. The incidence of grade 3-5 late
radiation injury in this study was 50% (11/22) and that of nasopharyngeal mucosal
necrosis was 31.8% (7/22). CONCLUSIONS: Endostar combined with chemoradiotherapy
may be effective in decreasing both the incidence of nasopharyngeal mucosal
necrosis. Studies with a larger sample size and longer follow-up are warranted.
PMID- 26418896
TI - Heme oxygenase-1 in macrophages controls prostate cancer progression.
AB - Innate immune cells strongly influence cancer growth and progression via multiple
mechanisms including regulation of epithelial to mesenchymal transition (EMT). In
this study, we investigated whether expression of the metabolic gene, heme
oxygenase-1 (HO-1) in tumor microenvironment imparts significant effects on
prostate cancer progression.We showed that HO-1 is expressed in MARCO-positive
macrophages in prostate cancer (PCa) xenografts and human prostate cancers. We
demonstrated that macrophage specific (LyzM-Cre) conditional deletion of HO-1
suppressed growth of PC3 xenografts in vivo and delayed progression of prostate
intraepithelial neoplasia (PIN) in TRAMP mice. However, initiation and
progression of cancer xenografts in the presence of macrophages lacking HO-1
resulted in loss of E-cadherin, a known marker of poor prognosis as well as EMT.
Application of CO, a product of HO-1 catalysis, increased levels of E-cadherin in
the adherens junctions between cancer cells. We further showed that HO-1-driven
expression of E-cadherin in cancer cells cultured in the presence of macrophages
is dependent on mitochondrial activity of cancer cells.In summary, these data
suggest that HO-1-derived CO from tumor-associated macrophages influences, in
part, E-cadherin expression and thus tumor initiation and progression.
PMID- 26418897
TI - The pan-HER family tyrosine kinase inhibitor afatinib overcomes HER3 ligand
heregulin-mediated resistance to EGFR inhibitors in non-small cell lung cancer.
AB - Afatinib is a second generation epidermal growth factor receptor-tyrosine kinase
inhibitor (EGFR-TKI) characterized as an irreversible pan-human EGFR (HER) family
inhibitor. Afatinib remains effective for a subpopulation of patients with non
small cell lung cancer (NSCLC) with acquired resistance to first generation EGFF
TKIs such as erlotinib. Heregulin activates HER3 in an autocrine fashion and
causes erlotinib resistance in NSCLC. Here we examine whether afatinib is
effective against heregulin-overexpressing NSCLCs harboring EGFR activating
mutations. Afatinib but not erlotinib decreased EGFR mutant NSCLC PC9HRG cell
proliferation in vitro and in mouse xenografts. Afatinib inhibited
phosphorylation of the cell signaling pathway proteins HER3, EGFR, HER2, and
HER4, likely by prevention of trans-phosphorylation as HER3 kinase activity is
inadequate for auto-phosphorylation. Afatinib, unlike erlotinib, inhibited AKT
activation, resulting in elevated apoptosis in PC9HRG cells. Clinically, a
subpopulation of 33 patients with EGFR mutations and NSCLC who had received first
generation EGFR-TKIs exhibited elevated plasma heregulin levels compared to
healthy volunteers; one of these achieved a response with afatinib therapy
despite having previously developed erlotinib resistance. Afatinib can overcome
heregulin-mediated resistance to erlotinib in EGFR mutant NSCLC. Further studies
are necessary to determine whether heregulin can predict afatinib efficacy after
development offirst generation EGFR-TKI resistance.
PMID- 26418898
TI - Induction of methionine adenosyltransferase 2A in tamoxifen-resistant breast
cancer cells.
AB - We previously showed that S-adenosylmethionine-mediated hypermethylation of the
PTEN promoter was important for the growth of tamoxifen-resistant MCF-7 (TAMR-MCF
7) cancer cells. Here, we found that the basal expression level of methionine
adenosyltransferase 2A (MAT2A), a critical enzyme for the biosynthesis of S
adenosylmethionine, was up-regulated in TAMR-MCF-7 cells compared with control
MCF-7 cells. Moreover, the basal expression level of MAT2A in T47D cells, a TAM
resistant estrogen receptor-positive cell line was higher compared to MCF-7
cells. Immunohistochemistry confirmed that MAT2A expression in TAM-resistant
human breast cancer tissues was higher than that in TAM-responsive cases. The
promoter region of human MAT2A contains binding sites for nuclear factor-kappaB,
activator protein-1 (AP-1), and NF-E2-related factor 2 (Nrf2), and the activities
of these three transcription factors were enhanced in TAMR-MCF-7 cells. Both the
protein expression and transcriptional activity of MAT2A in TAMR-MCF-7 cells were
potently suppressed by NF-kappaB inhibition but not by c-Jun/AP-1 or Nrf2 knock
down. Interestingly, the expression levels of microRNA (miR)-146a and -146b were
diminished in TAMR-MCF-7 cells, and miR-146b transduction decreased NF-kappaB
mediated MAT2A expression. miR-146b restored PTEN expression via the suppression
of PTEN promoter methylation in TAMR-MCF-7 cells. Additionally, miR-146b
overexpression inhibited cell proliferation and reversed chemoresistance to 4
hydroxytamoxifen in TAMR-MCF-7 cells.
PMID- 26418899
TI - BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas.
AB - BPTF, a subunit of NURF, is well known to be involved in the development of
eukaryotic cell, but little is known about its roles in cancers, especially in
non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically
overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of
BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis
and arrested cell cycle progress from G1 to S phase. We also found that BPTF
knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt
proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins,
thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic
pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such
as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho
cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA
inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied
by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay
for tumor tissue microarrays of lung tumor tissues showed that BPTF
overexpression predicted a poor prognosis in the patients with lung
adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role
in cell growth and survival by targeting multiply signaling pathways in human
lung cancers.
PMID- 26418900
TI - Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant
epithelial ovarian carcinoma.
AB - This study was designed to investigate whether proton pump inhibitors (PPI, V
ATPase blocker) could increase the effect of cytotoxic agents in chemoresistant
epithelial ovarian cancer (EOC). Expression of V-ATPase protein was evaluated in
patients with EOC using immunohistochemistry, and patient survival was compared
based on expression of V-ATPase mRNA from a TCGA data set. In vitro, EOC cell
lines were treated with chemotherapeutic agents with or without V-ATPase siRNA or
PPI (omeprazole) pretreatment. Cell survival and apoptosis was assessed using MTT
assay and ELISA, respectively. In vivo experiments were performed to confirm the
synergistic effect with omeprazole and paclitaxel on tumor growth in orthotopic
and patient-derived xenograft (PDX) mouse models. Expression of V-ATPase protein
in ovarian cancer tissues was observed in 44 patients (44/59, 74.6%). Higher
expression of V-ATPase mRNA was associated with poorer overall survival in TCGA
data. Inhibition of V-ATPase by siRNA or omeprazole significantly increased
cytotoxicity or apoptosis to paclitaxel in chemoresistant (HeyA8-MDR, SKOV3-TR)
and clear cell carcinoma cells (ES-2, RMG-1), but not in chemosensitive cells
(HeyA8, SKOV3ip1). Moreover, the combination of omeprazole and paclitaxel
significantly decreased the total tumor weight compared with paclitaxel alone in
a chemoresistant EOC animal model and a PDX model of clear cell carcinoma.
However, this finding was not observed in chemosensitive EOC animal models. These
results show that omeprazole pretreatment can increase the effect of
chemotherapeutic agents in chemoresistant EOC and clear cell carcinoma via
reduction of the acidic tumor microenvironment.
PMID- 26418901
TI - The Acute Physiology and Chronic Health Evaluation IV, a New Scoring System for
Predicting Mortality and Complications of Severe Acute Pancreatitis.
AB - OBJECTIVES: Severe acute pancreatitis is associated with significant
morbidity/mortality; thus, the ability to predict hospital course is imperative.
An updated version of the Acute Physiology and Chronic Health Evaluation II
(APACHE), APACHE IV, has recently been validated. Unlike other versions, APACHE
IV uses hepatobiliary parameters and accounts for multiple comorbid conditions
and sedation. The intention of this study was to examine APACHE IV for predicting
mortality and secondary outcomes for pancreatitis in a prospective cohort. In
addition, we compared APACHE IV to APACHE II, Bedside Index for Severity in Acute
Pancreatitis, and Ranson criterion. METHODS: We prospectively collected
physiologic parameters for each scoring system in 266 patients with severe acute
pancreatitis from August 2011 to April 2014. Prognostic value of each score was
determined using the area under the receiver operating characteristic curve.
RESULTS: Among 266 patients, 59% were men, 52% were white, and 36.5% had alcohol
induced pancreatitis. Mortality occurred in 15 (5.6%), and an APACHE IV of 44 or
greater predicted mortality in 100% of cases. The receiver operating
characteristic curve for APACHE IV was 0.93 (confidence interval [CI], 0.88
0.97); APACHE II, 0.87 (CI, 0.80-0.94); Bedside Index for Severity in Acute
Pancreatitis, 0.86 (CI, 0.78-0.94); and Ranson criterion, 0.90 (CI, 0.94-0.96).
CONCLUSION: The APACHE IV is a valid means for predicting mortality and disease
related complications in acute pancreatitis.
PMID- 26418902
TI - Increased Serum Insulin Exposure Does Not Affect Age or Stage of Pancreatic
Adenocarcinoma Diagnosis in Patients With Diabetes Mellitus.
AB - OBJECTIVES: In considering whether medications that increase insulin levels
accelerate pancreatic adenocarcinoma (PC) development, we hypothesized that PC
patients with diabetes mellitus (DM) who used exogenous insulin or insulin
stimulating medications should have an earlier age at diagnosis or present with
more advanced disease. METHODS: Patients enrolled in our PC registry from June 1,
2003, to May 31, 2012, were stratified according to treatment solely with
insulin, insulin-stimulating medications, or insulin-independent medications. Age
at PC diagnosis, PC stage, and years between DM and PC diagnoses were analyzed
among the cohorts. RESULTS: Of 122 DM patients (mean age, 67.4 +/- 10.2 years),
the mean ages at PC diagnosis within the insulin-only (n = 40), insulin
stimulating (n = 11), insulin-independent (n = 71), and non-DM (n = 321) cohorts
were 68.7 +/- 10.5, 69.6 +/- 10.8, 66.3 +/- 9.7, and 65.5 +/- 10.5 years,
respectively. No significant difference among the age at PC diagnosis was
observed based on duration or type of DM treatment. There was no correlation
between PC stage and increased insulin exposure. CONCLUSIONS: Anti-DM medications
that increase exposure to insulin do not appear to accelerate PC development
using outcomes of mean age at PC diagnosis, PC stage, or duration between DM and
PC diagnoses.
PMID- 26418903
TI - Early Predictors of Fluid Sequestration in Acute Pancreatitis: A Validation
Study.
AB - OBJECTIVES: The primary aim of this retrospective study was to externally
validate predictors of increased fluid sequestration at 48 hours (FS48) in acute
pancreatitis (AP). METHODS: Patients admitted between January 10 and February 13
with a diagnosis of AP were evaluated. The FS48 was calculated as difference
between total fluid input and output in the first 48 hours. Predictors of FS48,
such as young age, alcoholic etiology, hemoconcentration, hyperglycemia, and
systemic inflammatory response syndrome (SIRS), and outcomes in AP, such as
increased length of stay, acute fluid collection(s), necrosis, and persistent
organ failure (POF), were defined in accordance with the previous study. Linear
regression analysis was performed to evaluate the association between predictors
and outcome. RESULTS: Two hundred twenty-seven AP patients (mean age, 48 years;
54% men) with a median FS48 of 4.2 L were evaluated. Age younger than 40 years,
alcoholic etiology, hemoconcentration, and SIRS independently predicted increased
FS48 (P < 0.05). Increased FS48 was associated with persistent SIRS and POF (P <
0.01). There was a significant trend between number of predictors and FS (P <
0.001). The presence of 4 predictors or more was associated with higher rates of
persistent SIRS and POF (P < 0.01). CONCLUSIONS: Our study validated 4 of 5
predictors of increased FS48 from the previous study. Presence of 4 predictors or
more and increased FS48 are both associated with persistent SIRS and POF.
PMID- 26418904
TI - Evaluation of the Added Value of Diffusion-Weighted Imaging to Conventional
Magnetic Resonance Imaging in Pancreatic Neuroendocrine Tumors and Comparison
With 68Ga-DOTANOC Positron Emission Tomography/Computed Tomography.
AB - OBJECTIVES: The aims of this study were to investigate the added value of
diffusion-weighted imaging (DWI) in pancreatic neuroendocrine tumor (pNET)
evaluation and to compare magnetic resonance imaging (MRI) to Ga-DOTANOC positron
emission tomography/computed tomography (PET/CT) results. METHODS: Morphological
MRI (T2-weighted [T2-w] + contrast-enhanced [CE] T1-w) and DWI (T2-w + DWI) and
Ga-DOTANOC PET/CT in 25 patients/30 pNETs were retrospectively evaluated. Per
patient and per-lesion detection rates (pDR and lDR, respectively) were
calculated. Apparent diffusion coefficient values were compared among pNET and
surrounding and normal pancreas (control group, 18 patients). Apparent diffusion
coefficient and standardized uptake value (SUV) values were compared among
different grading and staging groups. RESULTS: No statistically significant
differences in PET/CT and MRI session detection rates were found (morphological
MRI and DW-MRI, 88% pDR and 87% lDR; combined evaluation, 92% pDR and 90% lDR; Ga
DOTANOC PET/CT, 88% pDR and 80% lDR). Consensus reading (morphological/DW-MRI +
PET/CT) improved pDR and lDR (100%). Apparent diffusion coefficient mean value
was significantly lower compared with surrounding and normal parenchyma (P <
0.01). The apparent diffusion coefficient and SUV values of pNETs among different
grading and staging groups were not statistically different. CONCLUSIONS:
Conventional MRI, DW-MRI + T2-w sequences, and Ga-DOTANOC PET/CT can be
alternative tools in pNET detection. Diffusion-weighted MRI could be valuable in
patients with clinical suspicion but negative conventional imaging findings.
However, the consensus reading of the 3 techniques seems the best approach.
PMID- 26418905
TI - Correlation Between RAB27B and p53 Expression and Overall Survival in Pancreatic
Cancer.
AB - OBJECTIVES: RAB27B is a member of the Rab family GTPases involved in vesicle
trafficking, and p53 has recently been implicated in regulating the exosome
secretion pathway. Because exosome secretion plays an important role in
modulating tumor microenvironment and invasive growth, we hypothesized that
RAB27B and p53 expression might be associated with the aggressive behavior in
pancreatic ductal adenocarcinoma, one of the most deadly human malignancies.
METHODS: We determined protein expression of RAB27B and p53 in 260 pancreatic
tissues (186 malignant and 74 normal or benign) by immunohistochemistry analysis
on tissue microarray and their correlation with patients' clinical parameters and
overall survival. RESULTS: We found that a high RAB27B protein expression
(RAB27B) was significantly associated with perineural and vascular invasion, as
well as distant metastasis. Patients with a high RAB27B expression had
significantly poorer overall survival in both univariate and multivariate
analyses. A significant correlation between RAB27B and p53 expression was
observed. CONCLUSIONS: Our data indicate that RAB27B expression is an independent
prognostic marker for pancreatic ductal adenocarcinoma and suggest that RAB27B
regulated exosome secretion pathway represents a novel therapeutic target in
pancreatic cancer.
PMID- 26418906
TI - Extracorporeal Shock Wave Lithotripsy for Chinese Patients With Pancreatic
Stones: A Prospective Study of 214 Cases.
AB - OBJECTIVES: This study aims to evaluate prospectively the safety and efficacy of
extracorporeal shock wave lithotripsy (ESWL) in Chinese patients. METHODS: A
total of 214 patients with painful chronic pancreatitis and pancreatic stones who
underwent ESWL followed by endoscopic retrograde cholangiopancreatography from
March 2011 to February 2012 in Changhai Hospital were enrolled. The main
pancreatic duct clearance rate and complications were recorded prospectively.
Symptoms, weight, quality of life, and pancreatic function were assessed before
and after ESWL and endotherapy. RESULTS: A total of 473 ESWL procedures were
performed in 214 patients. Stones were fragmented in all cases. Complete
clearance of main pancreatic duct stones and successful endoscopic decompression
were achieved in 155 (72.4%) and 188 (90.8%) of 214 patients, respectively.
Complications were observed after 20 sessions (20 of 473, 4.23%). Follow-up (n =
195) after 18.5 +/- 3.3 months showed that complete and partial pain relief were
achieved in 71.3% and 24.0% of the patients, respectively. The scores for the
quality of life (5.8 +/- 1.7 vs 8.1 +/- 1.2, P < 0.05) and mental health from the
Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire
(62.2 +/- 21.5 vs 68.5 +/- 16.4, P < 0.05) improved after ESWL. CONCLUSIONS:
Thus, ESWL is a safe and effective method to treat Chinese patients with
pancreatic stones. This procedure can significantly improve the success rate of
endotherapy.
PMID- 26418907
TI - Stimulation of Central alpha2 Receptors Attenuates Experimental Necrotizing
Pancreatitis.
AB - OBJECTIVES: Severe necrotizing pancreatitis (SNP) is a disease with relevant
morbidity and mortality until today. No specific therapy is in sight. Central
alpha2 agonists such as clonidine and dexmedetomidine are known to have anti
inflammatory effects though the cholinergic anti-inflammatory pathway and are
implemented in the clinical routine as adjunct sedative drugs. Their potential
effect on SNP has not yet been tested. METHODS: Severe necrotizing pancreatitis
was induced in male Wistar rats. Four treatment groups received either clonidine
or dexmedetomidine before (prophylactic) or after induction of SNP (therapeutic).
After 12 hours, pancreatic morphologic injury, systemic proinflammatory high
mobility group box 1 protein, and pancreatic and pulmonary myeloperoxidase levels
were evaluated. RESULTS: Severe necrotizing pancreatitis was fully established 12
hours after induction. "Prophylactic" and "therapeutic" administration of
clonidine and dexmedetomidine reduced pancreatic morphologic injury (P < 0.05 vs
SNP), serum proinflammatory high-mobility group box 1 protein (P < 0.0001 vs
SNP), as well as pancreatic and pulmonary myeloperoxidase levels (P < 0.01 vs
SNP). CONCLUSIONS: Prophylactic and therapeutic applications of the central
alpha2 agonists clonidine and dexmedetomidine are effective to attenuate local
and systemic injury in experimental SNP and should be evaluated in the clinical
setting.
PMID- 26418908
TI - Eotaxin-3 (CCL26) Expression in Human Pancreatic Myofibroblasts.
AB - OBJECTIVES: Eosinophil infiltration is a histological feature of autoimmune
pancreatitis (AIP). However, little is known about the mechanisms underlying
eosinophilic infiltration. In this study, we aimed to investigate the expression
of the eosinophil chemotactic protein, eotaxin-3, in human pancreatic
myofibroblasts. METHODS: Enzyme-linked immunosorbent assays and quantitative
polymerase chain reactions were used to quantify eotaxin-3 protein and messenger
RNA levels, respectively. RESULTS: Eotaxin-3 expression was induced by T helper
type 2 cytokines, interleukin-4 (IL-4) and IL-13, in time- and dose-dependent
manners. Both IL-4 and IL-13 induced the rapid phosphorylation of STAT6 (signal
transducer and activator of transcription 6), and STAT6-specific small
interfering RNA significantly blocked IL-4- and IL-13-induced eotaxin-3
expression, indicating involvement of STAT6 signaling pathways in eotaxin-3
induction. In contrast, SOCS (suppressor of cytokine signaling) protein-specific
small interfering RNA experiments suggested that the SOCS family proteins are
negative regulators of IL-4- and IL-13-induced eotaxin-3 expression in pancreatic
myofibroblasts. Interferon-gamma significantly inhibited IL-4- and IL-13-induced
eotaxin-3 expression, and this response was mediated by STAT1 activation.
CONCLUSIONS: Pancreatic myofibroblasts may be a cellular source of eotaxin-3 in
the pancreas. The T helper type 2 cytokines, IL-4 and IL-13, are critical factors
for the induction of eotaxin-3 in the pancreas.
PMID- 26418909
TI - Association and Intragenic Single-Nucleotide Polymorphism Interactions of the
XRCC1 Polymorphisms for Pancreatic Cancer Susceptibility.
AB - OBJECTIVES: X-ray repair cross-complementing group 1 (XRCC1) gene is an important
candidate gene for influencing human cancer risks. This study examined the main
and interactive effect of 9 single-nucleotide polymorphisms (SNPs) (Arg194Trp,
Arg280His, Arg399Gln, c.1254C>T, c.1517G>C, c.1471G>A, C310T, 539del542, and
T1915C) of XRCC1 in contribution to pancreatic cancer (PC). METHODS: A total of
298 PC patients and 298 healthy controls were enrolled. Selected SNPs in XRCC1
were genotyped. The generalized multifactor dimensionality reduction method
investigated gene-gene interactions. RESULTS: Single-locus analyses showed that,
in the codominant model, the GO genotype of 539del542 might have a higher risk
for PC (odds ratio [OR], 1.47; 95% confidence interval [95% CI], 1.05-2.08). For
T1915C polymorphism, the TC and CC genotypes both had a higher risk for PC (OR,
1.76; 95% CI, 1.25-2.48; OR, 1.83; 95% CI, 1.05-3.19, respectively); and a
similar result was observed in the dominant model (OR, 1.77; 95% CI, 1.28-2.46).
A tendency of association between Arg280His and PC was also detected in the
dominant model (OR, 0.70; 95% CI, 0.48-1.00). Furthermore, the generalized
multifactor dimensionality reduction method showed that the 4-locus model was
significant, involving Arg280His, 539del542, T1915C, and c.1517G>C (P < 0.05).
CONCLUSIONS: Thus, XRCC1 polymorphisms may contribute to the risk of PC
independently or in an interactive manner.
PMID- 26418910
TI - Metamizol Relieves Pain Without Interfering With Cerulein-Induced Acute
Pancreatitis in Mice.
AB - OBJECTIVES: Animal models are essential to understand the pathogenesis of acute
pancreatitis (AP) and to develop new therapeutic strategies. Although it has been
shown that cerulein-induced AP is associated with pain in experimental animals,
most experiments are carried out without any pain-relieving treatment because
researchers are apprehensive of an interference of the analgetic agent with AP
associated inflammation. In light of the growing ethical concerns and the legal
tightening regarding animal welfare during experiments, this attitude should be
changed. METHODS: Acute pancreatitis was induced by cerulein in the C57BL/6J and
FVB/N mouse inbred strains. One group received vehicle only, and the other was
treated with metamizol as analgetic agent. Pain sensation and parameters of AP
were analyzed as well as the effect of metamizol in the pancreas and its actions
in the brain. RESULTS: We report that oral administration of metamizol protects
cerulein-treated mice from abdominal pain without influencing the clinical and
histopathological course of the disease. In addition, it could be shown that
metamizol reduces the central pain response. CONCLUSIONS: This study reveals that
oral administered metamizol has no influence on the cerulein-induced AP and can
be given as an analgesic to increase animal welfare in experiments with induced
AP.
PMID- 26418911
TI - Time Trend of Outcomes for Severe Acute Pancreatitis After Publication of
Japanese Guidelines Based on a National Administrative Database.
AB - OBJECTIVES: This study aimed to investigate the recent time trend of outcomes for
severe acute pancreatitis after publication of Japanese guidelines based on a
national administrative database. METHODS: A total of 10,400 patients with severe
acute pancreatitis were referred to 1021 hospitals between 2010 and 2012 in
Japan. We collected patients' data from the administrative database to compare in
hospital mortality (within 28 days and overall), length of stay (LOS), and
medical costs during hospitalization. The study periods were categorized into 3
groups according to fiscal year: 2010 (n = 2698), 2011 (n = 3842), and 2012 (n =
3860). RESULTS: In-hospital mortality within 28 days and overall in-hospital
mortality were significantly decreased according to fiscal year (6.3% [2010] vs
5.7% [2011] vs 4.5% [2012], P = 0.005; 7.6% vs 7.1% vs 5.6%, P = 0.002,
respectively). However, mean LOS and medical costs were not different between
fiscal years (27.0 vs 27.1 vs 26.9 days, P = 0.218; 13,998.0 vs 14,156.4 vs
14,319.2 USD, P = 0.232, respectively). CONCLUSIONS: This study shows that
mortality of severe acute pancreatitis was reduced according to the time course,
whereas LOS or medical costs were stable after publication of the Japanese
guidelines.
PMID- 26418912
TI - Diagnostic Differentiation of Pancreatic Neuroendocrine Tumor From Other
Neoplastic Solid Pancreatic Lesions During Endoscopic Ultrasound-Guided Fine
Needle Aspiration.
AB - OBJECTIVES: To identify factors differentiating pancreatic neuroendocrine tumors
(PNETs) from non-PNET neoplastic solid pancreatic lesions (SPLs) and assess the
accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).
METHODS: This is a retrospective study at a tertiary center of consecutive
patients referred for EUS from 2004 to 2011. The main outcomes were pretest
predictors and accuracy of EUS-FNA for diagnosis of PNET. RESULTS: Among a total
of 1108 EUS-FNAs for pancreatic lesions, 672 patients (PNET = 91, non-PNET
neoplastic-SPLs = 581) had neoplastic-SPLs. The sensitivity, specificity, and
accuracy of EUS-FNA for diagnosis of PNETs were 98.9%, 100%, and 99.9%,
respectively. The mean needle-passes were 3.0/patient. The EUS volume (mean/year
per endosonographer) in preceding 3 years significantly correlated with fewer
needle passes (rs: [-0.26]; P = 0.02).Multivariate analysis demonstrated that
patients with PNET when compared to non-PNET neoplastic-SPLs were younger (odds
ratio [OR], 3.23; 95% confidence interval [95% CI], 1.19-9.09; P = 0.001), have 2
or more pancreatic lesions (OR, 5.63; 95% CI, 1.74-18.2; P = 0.005), and lower CA
19-9 values (OR, 10.0; 95% CI, 3.13-33.3; P = 0.001). Further, PNETs were less
likely to have weight loss (OR, 0.40; 95% CI, 0.17-0.90; P = 0.03), current
smoking (OR, 0.47; 95% CI, 0.22-0.98; P < 0.05), pancreatic ductal dilation (OR,
0.28; 95% CI, 0.13-0.60; P = 0.002), or imaging evidence of arterial invasion
(OR, 0.22; 95% CI, 0.07-0.71; P = 0.01). CONCLUSIONS: Although pre-FNA findings
can reliably characterize, EUS-FNA is highly accurate for the diagnosis of PNETs.
PMID- 26418913
TI - Effects of Caffeine and Lycopene in Experimentally Induced Diabetes Mellitus.
AB - OBJECTIVES: Diabetes mellitus (DM) is a global epidemic with increasing
prevalence. The disease is chronic in nature, and patients must use antidiabetic
drugs or insulin during their lifespan. Because of the difficulty of using
injectable insulin preparations, patients and practitioners prefer to use oral
antidiabetic drugs for prophylaxis and treatment. There are, however, numerous
adverse effects of antidiabetic drugs and rapidly increasing attention is being
paid to new nutraceutical drugs with fewer adverse effects. The purpose of this
study was to evaluate the effects of caffeine and lycopene on streptozotocin
(STZ)-induced DM in rats. METHODS: Caffeine and lycopene were administered to the
study groups by oral gavages for 1 month whereafter experimental diabetes was
induced in 90 rats in 6 groups. RESULTS: There were no pathological effects of
lycopene and caffeine on the pancreas. Marked vacuolization and degeneration were
observed in STZ-treated groups. Caffeine and lycopene decreased the pathological
findings and lowered the blood and urine glucose levels in the rats with STZ
induced DM, whereas these compounds increased serum insulin levels. CONCLUSIONS:
This study showed that caffeine and lycopene provided protective effects against
experimentally induced DM. The protective effects of lycopene were observed to be
much greater than those of caffeine.
PMID- 26418915
TI - The impact of environmental and biological factors on paraoxonase 1 and gamma
glutamyltranspeptydase activities in the blood of smelters.
AB - Disorders of paraoxonase and gamma-glutamyltranspeptydase activities can induce
development of the atherosclerotic process. The aim of the study was to examine
the effect of occupational exposure to heavy metals, tobacco smoke and alcohol
consumption on the activities of paraoxonase and gamma-glutamyltranspeptydase as
well as glutathione concentration. We have observed reduced paraoxonase activity
and higher gamma-glutamyltranspeptydase activity in serum of smelters when
compared to control groups. In the blood of smoking smelters was demonstrated a
negative correlation between paraoxonase activity and BMI value as well as
between paraoxonase activity and tobacco smoke and consumption of 40% alcohol.
Also, negative correlation was found for the activity of paraoxonase and
glutathione concentration as well as gamma-glutamyltranspeptydase activity.
Higher gamma-glutamyltranspeptydase activity and lower paraoxonase activity in
the serum of smelters exposed to heavy metals and tobacco smoke can cause
disorders in functioning of the body.
PMID- 26418916
TI - Does breastfeeding increase risk of early childhood caries?
AB - According to the WHO, "breastfeeding is the normal way of providing young infants
with the nutrients they need for healthy growth and development. Exclusive
breastfeeding is recommended up to 6 months of age, with continued breastfeeding
along with appropriate complementary foods up to two years of age or beyond".
However, several studies have reported prolonged and unrestricted breastfeeding
as a potential risk factor for primary tooth caries (ECC). On-demand
breastfeeding, particularly while lying down at night, would seem to cause ECC
because milk remains in the baby's mouth for long periods of time. There is lack
of evidence that human milk is cariogenic; other factors, such as oral hygiene,
may be more influential in caries development than on-demand breastfeeding.
Moreover the biomechanics of breastfeeding differs from those of bottle feeding
and milk is expressed into the soft palate and swallowed without remaining on
teeth. Indeed we cannot forget that the main factor influencing caries
development in infants is the presence of bacteria streptococcus mutans that
thrives in a combination of sugars, small amounts of saliva and a low pH. Today
the question is open and recently Chaffee, Felines, Vitolo et al. [2014] have
found that breastfeeding for 24 months or longer increases the prevalence of
severe early childhood caries in low-income families in Porto Alegre, Brazil.
These results do not claim that prolonged breastfeeding is the cause of tooth
decay; we can expect an association with food for infants often rich in refined
sugars, which cause the reduction of the protective effect of saliva on the
deciduous teeth enamel. In Japan, Kato, Yorifuji, Yamakawa et al. [2015] have
found that infants who had been breastfed for at least 6 or 7 months, both
exclusively and partially, were at elevated risk of dental caries at the age of
30 months compared with those who had been exclusively fed with formula. The
authors themselves say, however, that further studies with more elaborate methods
of assessment of breastfeeding may be necessary to determine the cariogenic
nature of breastfeeding. In the meantime, given the many benefits of
breastfeeding, the practice should continue to be strongly encouraged. Dental
professionals should encourage parents to start proper oral hygiene with their
children as soon as the first tooth erupts, and they should keep the intake of
sugary beverages to a minimum.
PMID- 26418917
TI - Serotype diversity of Streptococcus mutans and caries activity in children in
Argentina.
AB - AIM: The purpose of this study was to analyse the serotype distribution of S.
mutans and their association with caries activity in school children from
Cordoba, Argentina. MATERIALS AND METHODS: Clinical examination was performed in
133 children. The dmft+DMFT and Significant Caries (SiC) indices were calculated
to identify individuals with high caries activity. After DNA extractions of S.
mutans strains, serotypes were determined by PCR amplifications. The median
caries activity of each serotype group was compared using a non-parametric
Kruskall-Wallis test. RESULTS: We obtained S. mutans strains from stimulated
saliva of 94 children. The mean dmft+DMFT was 4.14 and the mean SiC index was
8.65. Serotype c was the most frequent (53.2%), followed by e (31.9%), f (8.5%)
and k (6.4%). The comparison between the SiC and Non-Sic groups showed
significant differences in the frequency of serotypes c and k. The median caries
activity was non-significant in the different serotypes. CONCLUSION: The
difference between the serotype frequencies detected in Argentina compared to
those of other countries could be related with contrasting dietary habits. The
results obtained in the present study would increase the knowledge about the
epidemiology of dental caries in children from Argentina.
PMID- 26418918
TI - CPP-ACP and CPP-ACFP versus fluoride varnish in remineralisation of early caries
lesions. A prospective study.
AB - AIM: To evaluate the effects of novel casein phosphopeptide (CPP) formulations
CPP-amorphous calcium phosphate (CCP- ACP) and CPP-amorphous calcium fluoride
phosphate (CPP-ACFP) versus fluoride varnish on the remineralisation of enamel
white spot lesions (WSLs) over a 12-week follow-up period. MATERIALS AND METHODS:
STUDY DESIGN: Double-blind prospective study. Eligibility criteria were patients
between 6 and 14 years old and have WSLs on their permanent teeth. We evaluated
786 WSLs. Participants were divided randomly into three groups. Groups A and B
were instructed to daily topical application of GC Tooth Mouse (CPP-ACP) or Mi
Paste Plus (CPP-ACFP), Group C received a monthly professional application of
Duraphat fluoride varnish. WSLs were categorised according to the International
Caries Detection and Assessment System (ICDAS II; grades 0-3) and assessed by
laser fluorescence (DIAGNOdent) at baseline and at 4, 8 and 12 weeks. Changes in
mineralisation before and after treatment were analysed using two-way analysis of
variance, with post hoc Bonferroni's non-parametric tests for multiple
comparisons. RESULTS: DIAGNOdent values were significantly reduced in Group B at
4 weeks, and in Groups A and C at 8 weeks. Mean values in Group B were lower than
in Groups A and C at 4 weeks, and lower than Group C at 8 weeks. CPP-ACFP
appeared to have a specific effect on smooth-surface caries, but no significant
effect on caries in pits and fissures. CONCLUSION: At 4 weeks, CPP-ACFP is
superior to fluoride varnish at remineralising smooth-surface WSLs. CPP-ACP is
not superior to fluoride varnish by any of the measures studied.
PMID- 26418919
TI - The reasons for extractions of primary teeth in Turkish children.
AB - AIM: The aim of this study was to determine the current reasons for primary teeth
extractions in Turkish children and their relative importance. MATERIALS AND
METHODS: STUDY DESIGN: retrospective evaluation of patients by analysing dental
records of children aged 2-13 years, receiving treatment in different regions in
Turkey over a period of five years (2007-2012). Patient's age, gender, any
significant medical finding, type of tooth extracted and the reason for the
extraction were the parameters evaluated. RESULTS: It resulted that 2,508 primary
teeth belonging to 1,755 children aged of 2-13 years were extracted. Extraction
due to caries (57,4%) was found to be the most common reason. STATISTICS: Chi
square tests were performed for statistical analysis. Although no differences in
the types of teeth extracted were observed between genders, striking differences
were noted in the different age groups. CONCLUSION: From this study it can be
concluded that caries and subsequent pulpal pathology are the most common reasons
for extraction of primary teeth in Turkey. Primary molars were the most common
tooth type extracted. Preventive programmes for preschool children should be
given importance.
PMID- 26418914
TI - Elucidation of the CHO Super-Ome (CHO-SO) by Proteoinformatics.
AB - Chinese hamster ovary (CHO) cells are the preferred host cell line for
manufacturing a variety of complex biotherapeutic drugs including monoclonal
antibodies. We performed a proteomics and bioinformatics analysis on the spent
medium from adherent CHO cells. Supernatant from CHO-K1 culture was collected and
subjected to in-solution digestion followed by LC/LC-MS/MS analysis, which
allowed the identification of 3281 different host cell proteins (HCPs). To
functionally categorize them, we applied multiple bioinformatics tools to the
proteins identified in our study including SignalP, TargetP, SecretomeP, TMHMM,
WoLF PSORT, and Phobius. This analysis provided information on the presence of
signal peptides, transmembrane domains, and cellular localization and showed that
both secreted and intracellular proteins were constituents of the supernatant.
Identified proteins were shown to be localized to the secretory pathway including
ones playing roles in cell growth, proliferation, and folding as well as those
involved in protein degradation and removal. After combining proteins predicted
to be secreted or having a signal peptide, we identified 1015 proteins, which we
termed as CHO supernatant-ome (CHO-SO), or superome. As a part of this effort, we
created a publically accessible web-based tool called GO-CHO to functionally
categorize proteins found in CHO-SO and identify enriched molecular functions,
biological processes, and cellular components. We also used a tool to evaluate
the immunogenicity potential of high-abundance HCPs. Among enriched functions
were catalytic activity and structural constituents of the cytoskeleton. Various
transport related biological processes, such as vesicle mediated transport, were
found to be highly enriched. Extracellular space and vesicular exosome associated
proteins were found to be the most enriched cellular components. The superome
also contained proteins secreted from both classical and nonclassical secretory
pathways. The work and database described in our study will enable the CHO
community to rapidly identify high-abundance HCPs in their cultures and therefore
help assess process and purification methods used in the production of biologic
drugs.
PMID- 26418920
TI - Management of impacted dilacerated maxillary incisor with strategic positioning
of a straightwire appliance.
AB - AIM: To describe the orthodontic management of root dilaceration of an impacted
maxillary tooth following trauma to its deciduous predecessors, to show the
clinical management of root dilaceration of a maxillary central incisor and
describe how the dilacerated tooth was successfully moved into alignment in a
young patient with a proper multidisciplinary approach, using the simple and
effective straightwire technique. CASE REPORT: After surgical exposure and
orthodontic traction, the impacted dilacerated tooth was brought to alignment in
the arch. The patient's chewing and speech function, and aesthetics were
restored. The radiograph shows that the root is finally straight and relatively
well developed. This approach avoids extraction and prosthetic rehabilitation of
the dilacerated tooth.
PMID- 26418921
TI - The care of traumatic dental injuries in primary schools in Southern Nigeria.
AB - AIM: To assess the standards of care given to children who sustain traumatic
dental injuries (TDI) in Nigerian primary schools. MATERIALS AND METHODS: STUDY
DESIGN: cross-sectional study. Public and private schools were selected from the
Southern geopolitical zones in Nigeria. An interviewer-administered questionnaire
was used to obtain information on the presence or absence of a school clinic,
trained nurse, records and first aid box from the head teachers. The record of
past traumatic dental injury, cause of the injury and treatment measures were
also obtained. STATISTICS: the information obtained were analysed using SPSS
version 20. RESULTS: There were 90 private and 90 public primary schools; 61
(34.1%) schools had school clinics. Forty-two (23.9%) of the schools had school
nurses (7 public and 35 private schools), and 27 (64.3%) of them had been trained
to treat dental emergencies. Only 14 (7.8%) of the schools had records of dental
injuries, and luxation injuries (31.6%) was the commonest injury. Children who
sustained injuries in the school premises were sent home in 59 (38.7%) schools,
while 36 (22.5%) and 37 (23.1%) schools were referred to physicians and dentists,
respectively. CONCLUSION: Many schools do not have school clinics/sick bays or
are poorly equipped to handle dental emergencies. Sending children home or to
health centres without first aid could affect the prognosis of dental injuries,
since timely intervention is of utmost importance for a successful outcome.
PMID- 26418923
TI - New techniques for producing aesthetic, direct full-crown composite resin
restorations for primary molars: a 24-month follow-up study of eight cases.
AB - AIM: Although the demand for aesthetic restoration of primary molars has
increased, techniques for producing aesthetic, direct full-crown restorations
using light-cured composite resin for primary molars and the associated clinical
outcome are not well established. The aim of this study was to describe the use
of new techniques to produce aesthetic, direct full-crown restorations using
light-cured composite resin for primary molars. The authors evaluate the clinical
outcomes of the restoration method and investigate whether this technique could
be used as an alternative to conventional methods. MATERIALS AND METHODS: Two new
techniques, the resin block and the clear matrix, were studied by treating 8
teeth. The occlusal surface of stainless steel crowns was used for impression
taking to facilitate accurate reproduction of the anatomic structure, and the
aesthetic restoration was obtained simply and consistently. RESULTS: At the 24
month follow-up evaluation, these new direct techniques were completely
satisfactory. Marginal discoloration was observed in one tooth treated with the
clear matrix technique, and a small partial wear was observed in another tooth
treated with the resin block. CONCLUSION: The new techniques for restoration
resulted in functional and aesthetic reproduction of occlusal morphology.
Therefore, these techniques could be considered a practical alternative to
conventional methods.
PMID- 26418922
TI - Inflammatory dentigerous cyst of mandibular first premolar associated with
endodontically treated primary first molar: a rare case report.
AB - AIM: Inflammatory dentigerous cysts usually occur in the mixed dentition. It has
been reported that inflammatory lesions from the root area of a deciduous tooth
bring about the development of dentigerous cysts around the unerupted permanent
tooth bud. Endodontic treatment is a common and successful procedure for
periapical inflammation in children. An inflammatory dentigerous cyst can occur
in conjunction with endodontically treated primary tooth. CASE REPORT: This
article reports a case of 6 years and 6 months old boy, with a single, well
defined, unilocular, radiolucent area enclosing the first right unerupted
mandibular premolar, accidentally discovered on the panoramic radiograph. The
first right primary molar had received a root canal treatment 18 months prior.
Clinical findings combined with radiographic and microscopic examinations
confirmed the diagnosis of inflammatory dentigerous cyst. As treatment,
enucleation of the cyst with removal of the involved permanent tooth was chosen
and a removable partial denture was supplied to the patient after surgery. The 5
year follow-up revealed good healing of the bony lesion and displaced teeth.
CONCLUSION: This case presented a severe and rare complication of endodontically
treated primary tooth, and the recommendation includes: (1) early diagnosis of
dentigerous cysts, which is essential to prevent extensive treatment; (2) more
information on the adverse side effects of an endodontic treatment should be
given to patients and parents; (3) patients should be informed about the
importance of follow-ups and radiographic follow-up should be routinised.
PMID- 26418924
TI - In vitro assessment of retention and microleakage in pit and fissure sealants
following enamel pre-etching with sodium hypochlorite deproteinisation.
AB - AIM: The purpose of this study was to assess and compare the rate of sealant
retention and microleakage after placement on etched enamel with and without
prior deproteinisation. MATERIALS AND METHODS: STUDY DESIGN: 75 freshly
extracted third molars were randomly assigned to either of two pit and fissure
treatment methods. Samples from both groups were etched with 37% phosphoric acid
gel for 15 seconds, followed by placement of a sealant, and then subjected to
thermocycling for evaluation of sealant retention. After that, specimens were
immersed in rhodamine B, sectioned longitudinally, and examined under a confocal
laser scanning microscope for assessment of microleakage. Collected data were
statistically analysed using chi-square and Fisher exact tests with an alpha
level of 0.05. RESULTS: The rate of sealant retention was similar between the two
study groups (P = 0.073), but the rate of sealant microleakage was significantly
lower in the enamel deproteinisation group (P < 0.001) than in the control group.
CONCLUSION: Based on these findings, we recommend the deproteinisation method
prior to enamel acid etching to obtain better clinical results with sealants.
PMID- 26418925
TI - Early treatment of Class III malocclusion with RME and facial mask: evaluation of
dentoalveolar effects on digital dental casts.
AB - AIM: To analyse the dental effects on digital dental casts in subjects with Class
III malocclusion treated with bonded Rapid Maxillary Expansion and Facial Mask
(RME/FM). MATERIALS AND METHODS: A study group sample (SG) of 29 subjects (13
females and 16 males) and mean age of 7.4 years (SD 1.2 years) was selected. A
bonded RME was placed and activated 1/4 of a turn per day until overcorrection of
the transverse width. At the end of expansion, patients were given FMs and
treated at least to a positive overjet. The SG was compared with a control group
(CG) of 21 prepubertal subjects (9 females; 12 males) presenting with normal
occlusion and mean age of 7.9 years (SD 1.6 years). For each subject of the SG
and CG initial (pretreatment, T1) and final (post-treatment, T2) digital dental
casts were available. Significant in between-group differences were tested with
the Student's t-test. RESULTS: The transverse dimension of the upper arch was
significantly greater in SG vs. CG (IMAW: +2.6 mm; ICAW: +3.1 mm). Anterior arch
length and arch depth were significantly smaller in SG when compared with CG
(AAL: -3.2 mm, AD: -3.4 mm) at the end of therapy. CONCLUSION: The orthopaedic
treatment with bonded RME/FM produced in subjects treated in the deciduous or
early mixed dentition a significant expansion of the maxillary arch and
mesialisation of the posterior teeth with a reduction of the arch depth.
PMID- 26418926
TI - New approach in paediatric dentistry: ultrasonic nondestructive evaluation of
restorative dental materials. Experimental study.
AB - AIM: The ultrasonic inspection is a non invasive method which is very developed
in the industrial field, for the non-destructive evaluation of materials, and in
the medical field, for the ultrasound diagnostic analysis. In paediatric
dentistry the most widely used non- destructive evaluation is the X-ray
technique. Radiographs are valuable aids in the oral health care of infants,
children, adolescents, allowing dentists to diagnose and treat oral diseases that
cannot be detected during a visual clinical examination. The aim of this in vitro
study was to analyse the ultrasonic non-destructive evaluation (UT-NDE) technique
to inspect both dental materials internal structure and the form and position of
internal defects in order to obtain a diagnostic method, free of ionising
radiations, in paediatric dentistry. Moreover the ultrasonic inspection (UT)
could be a rapid method of diagnosis in uncooperative paediatric patients.
MATERIALS AND METHODS: Study Design: Experimental samples were manufactured with
the characteristics of a large composite or glass ionomer cement paediatric
dental restoration, in terms of either size or operative technique used.
Characteristics of the common restorations were analysed and reproduced in vitro,
using the same operative conditions, also adding operative defects into some
samples. All the samples were subjected to an innovative UT test using the pulse
echo immersion scanning technique. Both C-scans and full volume scans were
carried out during the experimental programme. To enhance the data obtained from
the UT scan, a digital system (Ecus Inspection software) for signal detection,
archiving, processing and displaying was used. RESULTS: UT images showed the
presence of internal defects in the dental materials. It was also possible to
inspect very thin discontinuity such as the one represented by the fluid resin.
STATISTICS: In order to execute the statistical analysis, the values of electric
voltage measured in five higher white points and in five higher grey points of
the pictures pixels, were measured for each sample. Then, the average values and
the standardised data were calculated. CONCLUSION: n In conclusion, the
ultrasonic test could be a diagnostic non-invasive method in paediatric patients,
capable to evaluate the quality of the restorative teeth filling, showing
internal little defects. In vivo application of this diagnostic method should be
developed.
PMID- 26418927
TI - Prevalence of dental anomalies in children with cleft lip and unilateral and
bilateral cleft lip and palate.
AB - AIM: To examine the prevalence of different types of dental anomalies in children
with nonsyndromic cleft lip, unilateral cleft lip-palate, and bilateral cleft lip
palate. MATERIALS AND METHODS: A sample of 90 patients (aged 4-20 years) affected
by isolated cleft lip, unilateral and bilateral cleft lip and palate was
examined. Cleft patients were classified into one of three groups according to
cleft type: (1) Unilateral Cleft Lip-Palate, (2) Bilateral Cleft Lip-Palate, and
(3) Cleft Lip. Intraoral exams, panoramic radiographs and dental casts, were used
to analyse the prevalence of the various dental anomalies included in this study.
RESULTS: There were no statistically significant differences between patients
with cleft lip, unilateral cleft lip and palate and bilateral cleft lip and
palate. The congenital absence of the cleft-side lateral incisor was observed in
40% of the sample, and a total of 30% patients showed supernumerary teeth at the
incisors region. Second premolar agenesis was found in 4.4% of patients, whereas
in 18.9% of the sample there was an ectopic dental eruption. Lateral or central
incisors rotation was noted in 31.1% of the sample, while shape anomaly, lateral
incisor microdontia, and enamel hypoplasia were detected respectively in 25.6%,
5.6% and 18.9% of cleft patients. CONCLUSION: High prevalence of different dental
anomalies in children with cleft lip and unilateral and bilateral cleft lip and
palate has been confirmed. This study, in particular, shows the presence of
ectopic and rotated teeth in the cleft area.
PMID- 26418928
TI - Gingival fibromatosis: a case report.
AB - AIM: Gingival Fibromatosis is characterised by a large increase in the gingival
dimension which extends above the dental crowns, covering them partially or
completely. The causes of the disease may have a genetic origin, in which case
gingival hyperplasia may occur in isolation or be part of a syndrome, or acquired
origin, which comes from specific drugs administered systemically. A form of
gingival fibromatosis of idiopathic origin has been described. The therapy
involves mainly the surgical removal of the hyperplastic gingival tissue,
although in these cases recurrences are frequent. CASE REPORT: A 9 years old male
patient came to observation at the Clinic of Pediatric Dentistry of the Tor
Vergata Polyclinic of Rome. After Primary Gingival Fibromatosis was diagnosed,
the therapeutic choice was to wait and postpone gingivectomy at the end of the
development phase.
PMID- 26418929
TI - Evaluation of words in child-paediatric dentist communication.
AB - AIM: Aim of the present study is to demonstrate which words are widely used by
children and a paediatric dentist during different dental procedures in
conjunction with behaviour shaping in paediatric dentistry. MATERIALS AND
METHODS: Twenty children aged between 3.5 and 10.5 (10 F, 10 M) visiting the
clinic of Yeditepe University were enrolled for the study. An audio recorder was
hidden in the operatory room, the paediatric dentist was blind. The procedure was
randomised as for each child only one appointment was recorded (one patient-one
appointment-one procedure). Age, gender, appointment type, details of procedure
performed were recorded. At the end of every session, records were investigated
regarding verbal communication. RESULTS: The paediatric dentist used a total of
5,005 words during the trial with minimum of 13 and max of 518 words in a session
(mean 211.8 +/- 153.1). There were no significant differences in the words used
by the child and the practitioner regarding gender, session, and duration of
being acquainted with (p>0.05). Regarding age groups, preschoolers (3.5-6 yrs
old) significantly used more words than the schoolers (7- 10.5 yrs old) (p<0.05).
CONCLUSION: Paediatric dentists should be careful and selective in communication
with children as well as using an age-appropriate language.
PMID- 26418930
TI - Effect of audiovisual eyeglasses during dental treatment in 5-8 year-old
children.
AB - AIM: To evaluate the effect of Audiovisual (AV) eyeglasses on pain and anxiety
levels during restorative treatment in 5-8 year-olds Thai children. MATERIALS AND
METHODS: STUDY DESIGN: Forty-two children with bilateral carious molars were
recruited and randomly divided into 2 groups according to the sequence of AV
eyeglasses used. Group I was a group which received treatment without wearing AV
eyeglasses in the first visit and wearing the eyeglasses in a second visit. Group
II was vice versa. Treatments were done in 2 visits, 1 to 4 weeks apart. Self
reporting pain using the Faces Pain Scale-Revised (FPS-R), face, legs, activity,
crying and consolability scale (FLACC) and heart rate (HR), were measured to
assess pain and anxiety levels, respectively. Besides baseline, all variables
were measured at the following periods: 1) pre-operation, 2) rubber dam
placement, 3) the first use of high speed hand piece, and 4) five minutes
interval during the remaining treatment. RESULTS: There was no significant
difference in gender (p=0.204) and treatment arch (p=0.292) using Chi-square test
at p<0.05, previous dental experience (p=0.381) and treatment received (p=0.835)
using Fisher's exact test at p<0.05, age (p=0.384, T-test at p<0.05), and
treatment time (1st visit: p=0.465, 2nd visit: p=0.89, Mann- Whitney U test at
p<0.05) between 2 groups. AV eyeglasses effectively reduced HR in pre-operation
(p=0.043, T test at p<0.05) and FLACC scores in pre-operation (p=0.018, Mann
Whitney U test at p<0.05) and during the first use of high speed hand piece
(p=0.047, Mann-Whitney U test at p<0.05). However, HR were decreased during
rubber dam placement (p=0.002, T test at p<0.0), the first use of high speed hand
piece (p=0.049, T test at p<0.05) and during remaining treatment (p=0.035, T test
at p<0.05) in second visit as compared with the first visit with or without
wearing the eyeglasses. CONCLUSION: AV eyeglasses successfully reduced HR and
physical distress during pre-operation and the first use of high speed hand
piece. It could be used as an adjunctive distraction technique during dental
treatment in children.
PMID- 26418932
TI - [Poems from the clinic--afterwards].
PMID- 26418931
TI - The mandibular permanent second molars and their risk of impaction: a
retrospective study.
AB - AIM: The aim of this retrospective study is promote a better understanding of the
impaction of teeth 37 and 47 by means of clinical and statistical data from the
point of view of early interceptive treatment. MATERIALS AND METHODS: STUDY
DESIGN: 478 patients of the Orthodontic School of "La Sapienza" University of
Rome (Italy) were studied to assess the eruption of teeth 37 and 47 on at least
two good-quality panorex using angular measurements and Nolla's index from
January 2008 to December 2013. Data were analysed using ANOVA and Tukey HSD test
(P < 0.05). RESULTS: The data obtained on the possible correlations between the
examined teeth and the four reference angles show that at t0, the angular
variation of teeth 36 or 46 is constant when the teeth are at the end of their
eruptive process, while for teeth 37 and 47, this variation is always constant.
At t0, the first and the second molars of both quadrants, during eruption showed
a similar behaviour. At t1, the four teeth examined in the patients sample showed
a model of development analogous to that exhibited at t0. STATISTICS: a constant
variation (t0-t1) is present among the differences in the development of the 36
and the two angular values, while difference in development of the 37 and that of
the angular value is constant only in relationship to the difference in
development of the mandibular first molar of the same quadrant. The variations
between the difference in development of the 47 and in angular value (t0-t1) are
constant only when related to the developing 46. The analytic variance of
gradience (vargrad) data confirm peculiar behaviour of the first one, according
to both mandibular molars, during their eruptive development. CONCLUSIONS:
Adoption of universally recognised radiographic predictive methods allows
assessment of the case and allows the specialist to plan a suitable treatment to
prevent or intercept the molar impaction, with a perspective of a less invasive
and shorter therapy. Although rare, impaction of teeth 37 and 47 often requires a
complex, multidisciplinary approach.
PMID- 26418933
TI - [HbA1c is not enough in screening for impaired glucose metabolism. Glucose
tolerance tests are also needed, as shown in Swedish prospective epidemiological
study].
AB - An HbA1c threshold of >= 42 mmol/mol has been proposed to diagnose prediabetes.
The sensitivity, specificity and positive predictive value of the proposed
threshold for detection of individuals with prediabetes was examined in a study
of 573 randomly selected individuals from Vara and Skovde. In addition, the
utility of the FINDRISC questionnaire and of a fasting glucose test in
combination with three short questions concerning BMI, heredity for type 2
diabetes and known hypertension was examined. Results from an oral glucose
tolerance test were used as reference. The sensitivity of HbA1c and FINDRISC to
detect individuals with IGT was 16 and 26 per cent respectively. Questions
regarding BMI, heredity and hypertension together with a fasting glucose test
yielded a sensitivity of 50%, but a lower specificity and positive predictive
value. We conclude that HbA1c inefficiently detected individuals with impaired
glucose tolerance and that oral glucose tolerance tests can still preferably be
recommended.
PMID- 26418934
TI - [Good results of stent treatment in perforated duodenal ulcer].
AB - Despite modern treatment of ulcer disease perforations still occur and constitute
a life threatening complication. Standard treatment is surgical closure. We have
introduced stent treatment as a minimal invasive alternative, mainly in elderly
and co-morbid patients. During a 4-year period (2009-2012) ten patients with
perforated duodenal ulcer were treated with a covered duodenal stent at South
Alvsborg Hospital. These patients were retrospectively compared with all patients
(n = 19) treated with surgical closure at the same hospital during the same time
period. Stent treatment shows good clinical results indicating fewer
complications than surgical treatment even if the patients had a slightly higher
ASA score. In this series stent treatment is shown to be a safe and effective
alternative for treating perforated duodenal ulcers, even in old and co-morbid
patients.
PMID- 26418935
TI - [Glucose impairment despite normal HbA1c or fasting plasma glucose].
PMID- 26418936
TI - [No support for lipid therapy as an effective antidote in acute intoxication. A
systematic literature review and analysis of 114 case reports].
AB - Lipid rescue is increasingly used as treatment of various types of poisoning
despite weak scientific evidence. Some experimental studies have confirmed a
positive effect, but others have failed. Clinical studies are lacking, wherefore
we decided to do a systematic review of all published human cases. Case reports
were searched for in PubMed and Web of Science and thereafter examined by two
experts according to an assessment form grading the probability for a causal
connection between lipid rescue and improved symptoms. A total of 114 case
reports were identified. No correlation was found between the ratings of the
cases and the fat solubility of the respective toxins. The findings do not
support the predication that lipid rescue is an effective antidote, not even in
cases involving local anaesthetics. In view of the potentially negative effects
of lipid rescue, it seems reasonable to strictly limit its indication to life
threatening situations where conventional therapies have failed.
PMID- 26418937
TI - [Mimicking sounds--our first language?].
PMID- 26418938
TI - [Antidepressants--life-saving or life-threatening?].
PMID- 26418939
TI - ["Take responsibility for people who have undergone bariatric surgery".
Guidelines are lacking and follow-up needs radical improvement].
PMID- 26418941
TI - [The birth, life and death of value-based health care. The last "pseudo
innovation"?].
PMID- 26418940
TI - [The poet Brodsky passed through the purgatory of Soviet psychiatry].
PMID- 26418942
TI - [In Process Citation].
PMID- 26418943
TI - [A better follow-up of obesity surgery needed].
PMID- 26418944
TI - [Considering time].
PMID- 26418945
TI - ErbB4 Activated p38gamma MAPK Isoform Mediates Early Cardiogenesis Through NKx2.5
in Human Pluripotent Stem Cells.
AB - Activation of ErbB4 receptor signaling is instrumental in heart development, lack
of which results in embryonic lethality. However, mechanism governing its
intracellular signaling remains elusive. Using human pluripotent stem cells, we
show that ErbB4 is critical for cardiogenesis whereby its genetic knockdown
results in loss of cardiomyocytes. Phospho-proteome profiling and Western blot
studies attribute this loss to inactivation of p38gamma MAPK isoform which
physically interacts with NKx2.5 and GATA4 transcription factors. Post
cardiomyocyte formation p38gamma/NKx2.5 downregulation is followed by
p38alpha/MEF2c upregulation suggesting stage-specific developmental roles of p38
MAPK isoforms. Knockdown of p38gamma MAPK similarly disrupts cardiomyocyte
formation in spite of the presence of NKx2.5. Cell fractionation and NKx2.5
phosphorylation studies suggest inhibition of ErbB4-p38gamma signaling hinders
NKx2.5 nuclear translocation during early cardiogenesis. This study reveals a
novel pathway that directly links ErbB4 and p38gamma to the transcriptional
machinery of NKx2.5-GATA4 complex which is critical for cardiomyocyte formation
during mammalian heart development.
PMID- 26418946
TI - Pulmonary arterial wall thickness as a promising echocardiographic follow-up
parameter in severe pediatric pulmonary hypertension.
PMID- 26418947
TI - Continuous and pulsed hydrogen-deuterium exchange and mass spectrometry
characterize CsgE oligomerization.
AB - We report the use of hydrogen-deuterium amide exchange coupled to mass
spectrometry (HDX-MS) to study the interfaces of and conformational changes
accompanying CsgE oligomerization. This protein plays an important role in
enteric bacteria biofilm formation. Biofilms provide protection for enteric
bacteria from environmental extremes and raise concerns about controlling
bacteria and infectious disease. Their proteinaceous components, called curli,
are extracellular functional amyloids that initiate surface contact and biofilm
formation. The highly regulated curli biogenesis involves a major subunit, CsgA,
a minor subunit CsgB, and a series of other accessory proteins. CsgE, possibly
functioning as oligomer, is a chaperonin-like protein that delivers CsgA to an
outer-membrane bound oligomeric CsgG complex. No higher-order structure, or
interfaces and dynamics of its oligomerization, however, are known. In this work,
we determined regions involved in CsgE self-association by continuous HDX, and,
on the basis of that, prepared a double mutant W48A/F79A, derived from interface
alanine scan, and verified that it exists as monomer. Using pulsed HDX and MS, we
suggest there is a structural rearrangement occurring during the oligomerization
of CsgE.
PMID- 26418948
TI - Utilities of Electronic Medical Records to Improve Quality of Care for Acute
Kidney Injury: Past, Present, Future.
AB - Electronic health records (EHRs) have become an integrated part of medical
practice in most clinical settings around the world. Appropriate use of EHR
potentially improves patient care while poorly designed EHR can cause harm. In
recent years, EHR has been used as a platform to identify patients who have or
may develop acute kidney injury (AKI). The benefit of using EHR for a rule-based
classification of AKI has been controversial. While some reports indicate
improvement in the process of care provided to AKI patients, other studies do not
show significant changes in the outcomes. Utilities of EHR in AKI should go
beyond a rule-based detection of the AKI as a syndrome. There are several
different potential applications for such tools including AKI forecasting models
and clinical decision support systems, to improve the quality of care and outcome
of the patients with AKI. Both clinical and investigative interest in the field
is growing among clinicians, administrators and scientists. Appropriate
utilization of intelligent EHR can provide timely, appropriate and accurate
information to the clinicians in order to improve the quality of care provided to
critically ill patients and assist investigators to generate new knowledge. In
this review paper, we discuss the past and present states of EHR role in the
field of AKI. We also share our views regarding the future potentials and
directions of these devices.
PMID- 26418949
TI - Reply to comment by Ho on "genetic characterization, nickel tolerance,
biosorption, kinetics, and uptake mechanism of a bacterium isolated from
electroplating industrial effluent".
PMID- 26418950
TI - Apoptosis induced by temozolomide and nimustine in glioblastoma cells is
supported by JNK/c-Jun-mediated induction of the BH3-only protein BIM.
AB - The outcome of cancer therapy strongly depends on the complex network of cell
signaling pathways, including transcription factor activation following drug
exposure. Here we assessed whether and how the MAP kinase (MAPK) cascade and its
downstream target, the transcription factor AP-1, influence the sensitivity of
malignant glioma cells to the anticancer drugs temozolomide (TMZ) and nimustine
(ACNU). Both drugs induce apoptosis in glioma cells at late times following
treatment. Activation of the MAPK cascade precedes apoptosis, as shown by
phosphorylation of Jun kinase (JNK) and c-Jun, a main component of AP-1.
Pharmacological inhibition and siRNA mediated knockdown of JNK and c-Jun reduced
the level of apoptosis in LN-229 glioma cells treated with TMZ or ACNU. Analyzing
the underlying molecular mechanism, we identified the pro-apoptotic gene BIM as a
critical target of AP-1, which is upregulated following TMZ and ACNU.
Importantly, shRNA mediated downregulation of BIM in the malignant glioma cell
lines LN-229 and U87MG led to an attenuated cleavage of caspase-9 and,
consequently, reduced the level of apoptosis following TMZ and ACNU treatment.
Overall, we identified JNK/c-Jun activation and BIM induction as a late pro
apoptotic response of glioma cells treated with alkylating anticancer drugs.
PMID- 26418951
TI - Cytokine-induced killer cells efficiently kill stem-like cancer cells of
nasopharyngeal carcinoma via the NKG2D-ligands recognition.
AB - Cancer stem cells (CSCs) are considered to be the root cause for cancer treatment
failure. Thus, there remains an urgent need for more potent and safer therapies
against CSCs for curing cancer. In this study, the antitumor activity of cytokine
induced killer (CIK) cells against putative CSCs of nasopharyngeal carcinoma
(NPC) was fully evaluated in vitro and in vivo. To visualize putative CSCs in
vitro by fluorescence imaging, and image and quantify putative CSCs in tumor
xenograft-bearing mice by in vivo bioluminescence imaging, NPC cells were
engineered with CSC detector vector encoding GFP and luciferase (Luc) under
control of Nanog promoter. Our study reported in vitro intense tumor-killing
activity of CIK cells against putative CSCs of NPC, as revealed by percentage
analysis of side population cells, tumorsphere formation assay and Nanog-promoter
GFP-Luc reporter gene strategy plus time-lapse recording. Additionally, time
lapse imaging firstly illustrated that GFP-labeled or PKH26-labeled putative CSCs
or tumorspheres were usually attacked simultaneously by many CIK cells and
finally killed by CIK cells, suggesting the necessity of achieving sufficient
effector-to-target ratios. We firstly confirmed that NKG2D blockade by anti-NKG2D
antibody significantly but partially abrogated CIK cell-mediated cytolysis
against putative CSCs. More importantly, intravenous infusion of CIK cells
significantly delayed tumor growth in NOD/SCID mice, accompanied by a remarkable
reduction in putative CSC number monitored by whole-body bioluminescence imaging.
Taken together, our findings suggest that CIK cells demonstrate the intense tumor
killing activity against putative CSCs of NPC, at least in part, by NKG2D-ligands
recognition. These results indicate that CIK cell-based therapeutic strategy
against CSCs presents a promising and safe approach for cancer treatment.
PMID- 26418952
TI - Dendritic cell vaccination with a toll-like receptor agonist derived from
mycobacteria enhances anti-tumor immunity.
AB - Dendritic cell (DC)-based vaccines are considered useful in cancer immunotherapy,
and the interaction of DC and adjuvants is important in the design of the next
generation vaccines. In this study, whether DC combined with Rv2299c derived from
mycobacteria could improve anti-tumor immune responses in a colon cancer mouse
model was evaluated. MC38 cell lines were injected subcutaneously to establish
colon-cancer-bearing mice and the following four groups were evaluated: PBS
control, tumor antigen (TA) loaded-DC, Rv2299c, and a combination of TA-loaded-DC
and Rv2299c. The combination treatment with TA-loaded-DC and Rv2299c exhibited
greater inhibition of tumor growth compared to other groups. These effects were
associated with the reduction of suppressor cells, such as myeloid-derived
suppressor cells and regulatory T cells, and the induction of effector cells,
such as CD4+ T cells and CD8+ T cells, in spleen, and with the activation of
cytotoxic T Lymphocytes and NK cells. These results suggest that TA-loaded-DC
vaccination with Rv2299c derived from mycobacteria enhanced anti-tumor immunity
in a mouse colon cancer model by inhibiting the generation of immune-suppressive
cells and recovering numbers of effector cells, and demonstrated superior
polarization of the Th1/Th2 balance in favor of the Th1 immune response.
PMID- 26418953
TI - Molecular inimitability amongst tumors: implications for precision cancer
medicine in the age of personalized oncology.
AB - Tumor sequencing has revolutionized oncology, allowing for detailed interrogation
of the molecular underpinnings of cancer at an individual level. With this
additional insight, it is increasingly apparent that not only do tumors vary
within a sample (tumor heterogeneity), but also that each patient's individual
tumor is a constellation of unique molecular aberrations that will require an
equally unique personalized therapeutic regimen. We report here the results of
439 patients who underwent Clinical Laboratory Improvement Amendment (CLIA)
certified next generation sequencing (NGS) across histologies. Among these
patients, 98.4% had a unique molecular profile, and aside from three primary
brain tumor patients with a single genetic lesion (IDH1 R132H), no two patients
within a given histology were molecularly identical. Additionally, two sets of
patients had identical profiles consisting of two mutations in common and no
other anomalies. However, these profiles did not segregate by histology (lung
adenocarcinoma-appendiceal cancer (KRAS G12D and GNAS R201C), and lung
adenocarcinoma-liposarcoma (CDK4 and MDM2 amplification pairs)). These findings
suggest that most advanced tumors are molecular singletons within and between
histologies, and that tumors that differ in histology may still nonetheless
exhibit identical molecular portraits, albeit rarely.
PMID- 26418954
TI - EGFRvIII does not affect radiosensitivity with or without gefitinib treatment in
glioblastoma cells.
AB - BACKGROUND: Glioblastomas (GBM) are often characterized by an elevated expression
of the epidermal growth factor receptor variant III (EGFRvIII). We used GBM cell
lines with native EGFRvIII expression to determine whether this EGFR variant
affects radiosensitivity with or without EGFR targeting. METHODS: Experiments
were performed with GBM cell lines lacking (LN229, U87MG, U251, CAS-1) or
endogenously expressing EGFRvIII (BS153, DKMG). The two latter cell lines were
also used to establish sublines with a low (-) or a high proportion (+) of cells
expressing EGFRvIII. EGFR signaling and the cell cycle were analyzed using
Western blot and flow cytometry; cell survival was assessed by colony forming
assay and double-strand break repair capacity by immunofluorescence. RESULTS:
DKMG and BS153 parental cells with heterogeneous EGFRvIII expression were clearly
more radiosensitive compared to other GBM cell lines without EGFRvIII expression.
However, no significant difference was observed in cell proliferation,
clonogenicity or radiosensitivity between the EGFRvIII- and + sublines derived
from DKMG and BS153 parental cells. Expression of EGFRvIII was associated with
decreased DSB repair capacity for BS153 but not for DKMG cells. The effects of
EGFR targeting by gefitinib alone or in combination with irradiation were also
found not to depend on EGFRvIII expression. Gefitinib was only observed to
influence the proliferation of EGFRvIII- BS153 cells. CONCLUSION: The data
indicate that EGFRvIII does not alter radiosensitivity with or without anti-EGFR
treatment.
PMID- 26418955
TI - Mesenchymal Stromal Cells for Treatment of Acute Steroid-Refractory Graft Versus
Host Disease: Clinical Responses and Long-Term Outcome.
AB - Acute graft-versus-host disease (aGvHD) remains a major cause of morbidity and
mortality after allogeneic hematopoietic stem cell transplantation. Steroid
resistant aGvHD is associated with poor outcome, and no commonly accepted salvage
therapy is available for its treatment. Here, we report 58 adult patients treated
with mesenchymal stromal cells (MSCs) as salvage therapy for steroid-refractory
aGvHD. Third-party MSCs expanded in platelet lysate-containing medium were
transfused at a median dose of 0.99 * 10(6) cells per kg b.wt. A median of two
MSC infusions were administered to each patient. Median time between the onset of
aGvHD and the first infusion of MSCs was 12 days (range, 6-62 days). Most
patients (79%) had grade IV aGvHD. Five patients showed complete response, five
showed very good partial response, 17 showed partial response, and 31 showed no
response. The estimated probability of survival after 1 year was 19%, and median
survival was 69 days. Overall survival was not significantly different from that
of a historical cohort of patients receiving alternative salvage therapy and no
MSC infusions. In conclusion, MSC treatment on top of conventional
immunosuppression was associated with an overall response rate of 47% but
improved outcome in terms of survival remains to be shown.
PMID- 26418956
TI - The Na+/Ca2+ Exchanger 1 (NCX1) Variant 3 as the Major Extrusion System in Renal
Distal Tubular Transcellular Ca2+-Transport.
AB - BACKGROUND/AIMS: Fine-tuning of renal calcium (Ca(2+)) reabsorption takes place
in the late distal convoluted and connecting tubules (DCT2/CNT) of the kidney via
transcellular Ca(2+) transport. Here, Ca(2+) enters the cell at the apical side
via the epithelial Ca(2+) channel transient receptor potential vanilloid 5 and is
subsequently extruded at the basolateral side by the concerted actions of the
plasma membrane Ca(2+) ATPases and the Na(+)/Ca(2+) exchanger 1 (NCX1). NCX1 is
responsible for ~ 70% of basolateral Ca(2+) extrusion. The aim of this study was
to determine the predominant NCX1 variant in the kidney and its role in Ca(2+)
transport. METHODS: DCT2/CNT specific tubules were used to show the abundance of
NCX1 specific isoforms. Renal NCX1 variants were cloned from mouse kidney tissue.
Human Embryonic Kidney 293(T) cells were transiently transfected with NCX1.3, and
Fura-2 measurements and 45Ca(2+) uptake assays were performed to determine
several characteristics of NCX1.3 in the reverse mode. RESULTS: NCX1.3 was
demonstrated to be the predominant NCX1 variant in the DCT2/CNT, next to NCX1.2
and NCX1.7. NCX1.3 could be inhibited by SN-6, an NCX-specific inhibitor, whereas
stimulation of the cAMP/PKA or PKC-mediated pathway did not affect Ca(2+) influx
as measured in the reverse mode. Lowering intracellular Ca(2+) concentrations
resulted in a decreased Ca(2+) uptake. CONCLUSION: NCX1.3 is the predominant NCX
variant in the DCT2/CNT tubules. Its function is dependent on intracellular
Ca(2+) concentrations.
PMID- 26418959
TI - Brain Activation for Knee Movement Measured Days Before Second Anterior Cruciate
Ligament Injury: Neuroimaging in Musculoskeletal Medicine.
AB - BACKGROUND: Anterior cruciate ligament (ACL) injury has multifactorial causes
encompassing mechanical, hormonal, exposure, and anatomical factors. Alterations
in the central nervous system also play a role, but their influence after injury,
recovery, and recurrent injury remain unknown. Modern neuroimaging techniques can
be used to elucidate the underlying functional and structural alterations of the
brain that predicate the neuromuscular control adaptations associated with ACL
injury. This knowledge will further our understanding of the neural adaptations
after ACL injury and rehabilitation and in relation to future injury risk. In
this paper, we describe the measurement of brain activation during knee extension
flexion after ACL injury and reconstruction and 26 days before a contralateral
ACL injury. METHODS: Brain functional magnetic resonance imaging data for an
ACL-injured participant and a matched control participant were collected and
contrasted. RESULTS: Relative to the matched control participant, the ACL
injured participant exhibited increased activation of motor planning, sensory
processing, and visual-motor control areas. A similar activation pattern was
present for the contralateral knee that sustained a subsequent injury.
CONCLUSIONS: Bilateral neuroplasticity after ACL injury may contribute to risk
of second injury, or aspects of neurophysiology may be predisposing factors to
primary injury. CLINICAL IMPLICATIONS: Sensory-visual-motor function and motor
learning adaptations may provide targets for rehabilitation.
PMID- 26418958
TI - Joint Kinetics and Kinematics During Common Lower Limb Rehabilitation Exercises.
AB - CONTEXT: Unilateral body-weight exercises are commonly used to strengthen the
lower limbs during rehabilitation after injury, but data comparing the loading of
the limbs during these tasks are limited. OBJECTIVE: To compare joint kinetics
and kinematics during 3 commonly used rehabilitation exercises. DESIGN:
Descriptive laboratory study. SETTING: Laboratory. PATIENTS OR OTHER
PARTICIPANTS: A total of 9 men (age = 22.1 +/- 1.3 years, height = 1.76 +/- 0.08
m, mass = 80.1 +/- 12.2 kg) participated. INTERVENTION(S): Participants performed
the single-legged squat, forward lunge, and reverse lunge with kinetic data
captured via 2 force plates and 3-dimensional kinematic data collected using a
motion-capture system. MAIN OUTCOME MEASURE(S): Peak ground reaction forces,
maximum joint angles, and peak sagittal-joint moments. RESULTS: We observed
greater eccentric and concentric peak vertical ground reaction forces during the
single-legged squat than during both lunge variations (P <= .001). Both lunge
variations demonstrated greater knee and hip angles than did the single-legged
squat (P < .001), but we observed no differences between lunges (P > .05).
Greater dorsiflexion occurred during the single-legged squat than during both
lunge variations (P < .05), but we noted no differences between lunge variations
(P = .70). Hip-joint moments were greater during the forward lunge than during
the reverse lunge (P = .003) and the single-legged squat (P = .011). Knee-joint
moments were greater in the single-legged squat than in the reverse lunge (P <
.001) but not greater in the single-legged squat than in the forward lunge (P =
.41). Ankle-joint moments were greater during the single-legged squat than during
the forward lunge (P = .002) and reverse lunge (P < .001). CONCLUSIONS:
Appropriate loading progressions for the hip should begin with the single-legged
squat and progress to the reverse lunge and then the forward lunge. In contrast,
loading progressions for the knee and ankle should begin with the reverse lunge
and progress to the forward lunge and then the single-legged squat.
PMID- 26418960
TI - Effect of ferromagnetic ordering on phonons in KCo2Se2.
AB - Results of the density functional theory studies of the phonon dynamics in the
ternary layered cobalt diselenide are reported. The partial phonon densities of
states due to vibrations of K, Co, and Se atoms are analysed in detail. They
indicate that phonons associated with the dynamics of Co and Se ions within the
[Co2Se2] structural blocks span the entire spectral range extending to 260 cm(
1), whereas phonons from the K-sublattice remain limited to the frequency range
of 80-150 cm(-1). The phonons conform with structural features of the quasi-2D
layered structure of KCo2Se2. Ferromagnetic order in the Co-sublattice is shown
to determine to a great extent the phonon densities of states, the Raman and
infrared spectra of KCo2Se2. The in-planar magnetic interactions are responsible
for pronounced softening of the high-frequency phonon modes and lead to
disappearance of the low-frequency Raman-active mode of the E g symmetry. The
observed behavior of the Raman-active and infrared-active modes suggests rather
strong spin-phonon coupling in KCo2Se2. Results of the present investigations
allow to clarify the origin of substantial differences between dynamical
properties of the ferromagnetic Co-based and the paramagnetic Ni-based ternary
layered dichalcogenides, both adopting the ThCr2Si2-type structure.
PMID- 26418957
TI - A new balancing act: The many roles of melatonin and serotonin in plant growth
and development.
AB - Melatonin and serotonin are indoleamines first identified as neurotransmitters in
vertebrates; they have now been found to be ubiquitously present across all forms
of life. Both melatonin and serotonin were discovered in plants several years
after their discovery in mammals, but their presence has now been confirmed in
almost all plant families. The mechanisms of action of melatonin and serotonin
are still poorly defined. Melatonin and serotonin possess important roles in
plant growth and development, including functions in chronoregulation and
modulation of reproductive development, control of root and shoot organogenesis,
maintenance of plant tissues, delay of senescence, and responses to biotic and
abiotic stresses. This review focuses on the roles of melatonin and serotonin as
a novel class of plant growth regulators. Their roles in reproductive and
vegetative plant growth will be examined including an overview of current
hypotheses and knowledge regarding their mechanisms of action in specific
responses.
PMID- 26418961
TI - Interleukin-2, Ipilimumab, and Anti-PD-1: Clinical Management and the Evolving
Role of Immunotherapy for the Treatment of Patients With Metastatic Melanoma.
AB - Treatment of metastatic melanoma has changed dramatically in the past 5 years
with the approval of six new agents (vemurafenib, dabrafenib, trametinib,
ipilimumab, pembrolizumab, and nivolumab) by the US Food and Drug Administration
(FDA). This review will compare the immunotherapies recently approved by the FDA
(ipilimumab, nivolumab and pembrolizumab) with the long-approved immunotherapy,
interleukin-2. Additional consideration will be given to the evolving landscape,
including the opportunities for combination regimens. Immunotherapies have
distinct mechanisms of action and unique response kinetics that differ from
conventional cytotoxic and targeted therapies, and have a range of adverse events
that can be safely managed by experienced health care providers. Data suggest
immunotherapies can result in long-term survival in a proportion of patients.
This dynamic and evolving field of immunotherapy for melanoma will continue to
offer challenges in terms of optimal patient management for the foreseeable
future.
PMID- 26418962
TI - Irradiation Enhances the Ability of Monocytes as Nanoparticle Carrier for Cancer
Therapy.
AB - The tumor-homing ability of monocytes renders them a potential cellular delivery
system for alternative cancer therapies, although their migratory ability can be
impaired following reagent uptake. Approaches that enhance monocyte tumor homing
and promote their migration will improve the clinical value of these cells as
cellular carriers. Previous studies have shown that irradiation (IR) can promote
macrophage aggregation in hypoxic regions. To investigate whether IR enhances the
infiltration of bone marrow-derived monocytes (BMDMs) into tumors, the
infiltration of BMDMs from GFP-transgenic mice in a murine prostate
adenocarcinoma TRAMP-C1 model was examined by fluorescence microscopy. IR did not
increase the number of BMDMs that infiltrated initially, but did increase
monocyte retention within IR-treated tumors for up to 2 weeks. We also showed
that BMDMs can take up various imaging and therapeutic agents, although the
mobility of BMDMs decreased with increasing load. When BMDMs were differentiated
in IR-treated tumor-conditioned medium (IR-CM) in vitro, the nanoparticle load
mediated inhibition of migration was attenuated. These IR-CM-differentiated BMDMs
delivered polymer vesicles encapsulating doxorubicin to radiation therapy (RT)
induced hypoxic tumor regions, and enhanced the efficacy of RT. The prolonged
retention of monocytes within irradiated tumor tissues and the ability of IR-CM
to enhance the migratory ability of cargo-laden BMDMs suggest that monocytes pre
conditioned by IR-CM can potentially act as cellular carriers for targeted
therapy following conventional RT.
PMID- 26418963
TI - Endoplasmic reticulum: Where nucleotide sugar transport meets cytokinin control
mechanisms.
AB - The endoplasmic reticulum (ER) is a multifunctional eukaryotic organelle where
the vast majority of secretory proteins are folded and assembled to achieve their
correct tertiary structures. The lumen of the ER and Golgi apparatus also
provides an environment for numerous glycosylation reactions essential for
modifications of proteins and lipids, and for cell wall biosynthesis. These
glycosylation reactions require a constant supply of cytosolically synthesized
substrate precursors, nucleotide sugars, which are transported by a group of
dedicated nucleotide sugar transporters (NST). Recently, we have reported on the
identification of a novel ER-localized NST protein, ROCK1, which mediates the
transport of UDP-linked acetylated hexosamines across the ER membrane in
Arabidopsis. Interestingly, it has been demonstrated that the activity of ROCK1
is important for the regulation of cytokinin-degrading enzymes, cytokinin
oxidases/dehydrogenases (CKX), in the ER and, thus, for cytokinin responses. In
this addendum we will address the biochemical and cellular activity of the ROCK1
transporter and its phylogenetic relation to other NST proteins.
PMID- 26418965
TI - Method for the Synthesis of Dibenzo[g,p]Chrysenes: Domino Friedel-Crafts-Type
Cyclization of Difluoroethenes Bearing Two Biaryl Groups.
AB - Dibenzo[g,p]chrysenes were readily synthesized via the superacid- or TiF4
mediated domino Friedel-Crafts-type cyclization of 1,1-difluoroethenes bearing
two biaryl groups, which were easily prepared via the Suzuki-Miyaura coupling of
1,1-difluoro-2,2-diiodoethene or 1-(biphenyl-2-yl)-1-bromo-2,2-difluoroethene.
Using this approach, the activation of both vinylic and aromatic C-F bonds was
successfully achieved to make new C-C bonds.
PMID- 26418964
TI - A Sensitive and Biodegradable Pressure Sensor Array for Cardiovascular
Monitoring.
AB - An array of highly sensitive pressure sensors entirely made of biodegradable
materials is presented, designed as a single-use flexible patch for application
in cardiovascular monitoring. The high sensitivity in combination with fast
response time is unprecedented when compared to recent reports on biodegradable
pressure sensors (sensitivity three orders of magnitude higher), as illustrated
by pulse wave velocity measurements, toward hypertension detection.
PMID- 26418967
TI - A Model to Estimate Frozen Tissue Collection Targets in Biobanks to Support
Cancer Research.
AB - Human biospecimens are used in 40% of cancer research publications. Tumor
biobanks are an important source for these biospecimens and support both
prospective and retrospective research studies. Supporting retrospective research
requires tumor tissue biobanks to accrue an adequate inventory, or stock, of
cases comprising tumor biospecimens and associated treatment and outcomes data.
We propose a model to establish appropriate targets for stocks of frozen tissue
biospecimens in tumor biobanks, sufficient to support cancer research needs. Our
model considers national levels of investment in academic cancer research
relative to research use of cases described in publication output, and scales
this to the local context of the BC Cancer Agency Tumour Tissue Repository (TTR)
as an example. Adjustment factors are then applied to correct for the primary
intended user base of the biobank, as well as variables intrinsic to all
biobanking operations and case collection. On this basis we estimate a current
target stock for the TTR of approximately 4500 cases. Local research demand
derived from case release data can then be applied to fine-tune accrual targets
and refine the biobank's relative portfolio of cases from different tumor sites.
We recognize that current targets will need regular remodeling as research
demands change over time and that our initial model has some limitations related
to the need to extrapolate from available research and biobank utilization data,
and does not incorporate biospecimen/case contributions within the context of a
network. However, we believe the lack of models to estimate inventory targets for
tumor biobanks and to better balance research demand with biospecimen supply,
contributes to the hesitation of funders to provide support, and also the
problems of sustainability faced by many biobanks. Creating tangible inventory
targets will improve biobank efficiency, sustainability, and may also encourage
increased and stable funding.
PMID- 26418966
TI - Novel 3-Substituted 7-Phenylpyrrolo[3,2-f]quinolin-9(6H)-ones as Single Entities
with Multitarget Antiproliferative Activity.
AB - A series of chemically modified 7-phenylpyrrolo[3,2-f]quinolinones was
synthesized and evaluated as anticancer agents. Among them, the most cytotoxic
(subnanomolar GI50 values) amidic derivative 5f was shown to act as an inhibitor
of tubulin polymerization (IC50, 0.99 MUM) by binding to the colchicine site with
high affinity. Moreover, 5f induced cell cycle arrest in the G2/M phase of the
cell cycle in a concentration dependent manner, followed by caspase-dependent
apoptotic cell death. Compound 5f also showed lower toxicity in nontumoral cells,
suggesting selectivity toward cancer cells. Additional experiments revealed that
5f inhibited the enzymatic activity of multiple kinases, including AURKA, FLT3,
GSK3A, MAP3K, MEK, RSK2, RSK4, PLK4, ULK1, and JAK1. Computational studies showed
that 5f can be properly accommodated in the colchicine binding site of tubulin as
well as in the ATP binding clefts of all examined kinases. Our data indicate that
the excellent antiproliferative profile of 5f may be derived from its
interactions with multiple cellular targets.
PMID- 26418969
TI - Structural phase transitions in trigonal Selenium induce the formation of a
disordered phase.
AB - Arguments based on the Mermin-Wagner theorem suggest that the quasi-1D trigonal
phase of Se should be unstable against long wavelength perturbations. Consisting
of parallel Se-Se chains, this essentially fragile solid undergoes a partial
transition to a monoclinic structure (consisting of 8-membered rings) at low
temperatures (~50 K), and to a distorted trigonal phase at moderate pressures
(~3GPa). Experimental investigations on sub-millimeter-sized single crystals
provide clear evidence that these transitions occur via a novel and counter
intuitive route. This involves the reversible formation of an intermediate,
disordered structure that appears as a minority phase with increasing pressure as
well as with decreasing temperature. The formation of the disordered state is
indicated by: (a) a 'Boson-peak' that appears at low temperatures in the specific
heat and resonance Raman data, and (b) a decrease in the intensity of Raman lines
over a relatively narrow pressure range. We complement the experimental results
with a phenomenological model that illustrates how a first order structural
transition may lead to disorder. Interestingly, nanocrystals of trigonal Se do
not undergo any structural transition in the parameter space studied; neither do
they exhibit signs of disorder, further underlining the role of disorder in this
type of structural transition.
PMID- 26418968
TI - CD151 promotes alpha3beta1 integrin-dependent organization of carcinoma cell
junctions and restrains collective cell invasion.
AB - Integrins function in collective migration both as major receptors for
extracellular matrix and by crosstalk to adherens junctions. Despite extensive
research, important questions remain about how integrin signaling mechanisms are
integrated into collective migration programs. Tetraspanins form cell surface
complexes with a subset of integrins and thus are good candidates for regulating
the balance of integrin functional inputs into cell-matrix and cell-cell
interactions. For example, tetraspanin CD151 directly associates with alpha3beta1
integrin in carcinoma cells and promotes rapid alpha3beta1-dependent single cell
motility, but CD151 also promotes organized adherens junctions and restrains
collective carcinoma cell migration on 2D substrates. However, the individual
roles of CD151s integrin partners in CD151s pro-junction activity in carcinoma
cells were not well understood. Here we find that CD151 promotes organized
carcinoma cell junctions via alpha3beta1 integrin, by a mechanism that requires
the a3b1 ligand, laminin-332. Loss of CD151 promotes collective 3D invasion and
growth in vitro and in vivo, and the enhanced invasion of CD151-silenced cells is
alpha3 integrin dependent, suggesting that CD151 can regulate the balance between
alpha3beta1s pro-junction and pro-migratory activities in collective invasion. An
analysis of human cancer cases revealed that changes in CD151 expression can be
linked to either better or worse clinical outcomes depending on context,
including potentially divergent roles for CD151 in different subsets of breast
cancer cases. Thus, the role of the CD151-alpha3beta1 complex in carcinoma
progression is context dependent, and may depend on the mode of tumor cell
invasion.
PMID- 26418970
TI - Airborne signals of communication in sagebrush: a pharmacological approach.
AB - When plants receive volatiles from a damaged plant, the receivers become more
resistant to herbivory. This phenomenon has been reported in many plant species
and called plant-plant communication. Lab experiments have suggested that several
compounds may be functioning as airborne signals. The objective of this study is
to identify potential airborne signals used in communication between sagebrush
(Artemisia tridentata) individuals in the field. We collected volatiles of one
branch from each of 99 sagebrush individual plants. Eighteen different volatiles
were detected by GC-MS analysis. Among these, 4 compounds; 1.8-cineol, beta
caryophyllene, alpha-pinene and borneol, were investigated as signals of
communication under natural conditions. The branches which received either 1,8
cineol or beta-caryophyllene tended to get less damage than controls. These
results suggested that 1,8-cineol and beta-caryophyllene should be considered
further as possible candidates for generalized airborne signals in sagebrush.
PMID- 26418971
TI - Epidemiology of Pelvic Fractures in Germany: Considerably High Incidence Rates
among Older People.
AB - Epidemiological data about pelvic fractures are limited. Until today, most
studies only analyzed inpatient data. The purpose of this study was to estimate
incidence rates of pelvic fractures in the German population aged 60 years or
older, based on outpatient and inpatient data. We conducted a retrospective
population-based observational study based on routine data from a large health
insurance company in Germany. Age and sex-specific incidence rates of first
fractures between 2008 and 2011 were calculated. We also standardized incidence
rates with respect to age and sex in the German population. Multiple Poisson
regression models were used to evaluate the association between the risk of first
pelvic fracture as outcome and sex, age, calendar year and region as independent
variables. The total number of patients with a first pelvic fracture corresponded
to 8,041 and during the study period 5,978 insured persons needed inpatient
treatment. Overall, the standardized incidence rate of all first pelvic fractures
was 22.4 [95% CI 22.0-22.9] per 10,000 person-years, and the standardized
incidence rate of inpatient treated fractures 16.5 [16.1-16.9]. Our adjusted
regression analysis confirmed a significant sex (RR 2.38 [2.23-2.55], p < 0.001,
men as reference) and age effect (higher risk with increasing age, p < 0.001) on
first fracture risk. We found a slight association between calendar year (higher
risk in later years compared to 2008, p = 0.0162) and first fracture risk and a
further significant association with region (RR 0.92 [0.87-0.98], p = 0.006,
Westfalen-Lippe as reference). The observed incidences are considerably higher
than incidences described in the international literature, even if only inpatient
treated pelvic fractures are regarded. Besides which, non-inclusion of outpatient
data means that a relevant proportion of pelvic fractures are not taken into
account. Prevention of low energy trauma among older people remains an important
issue.
PMID- 26418973
TI - Polymer-Layer-Free Alignment for Fast Switching Nematic Liquid Crystals by
Multifunctional Nanostructured Substrate.
AB - A novel polymer-layer-free system for liquid-crystal alignment is demonstrated by
various shaped indium tin oxide (ITO) patterns. Liquid crystals are aligned along
the ITO line pattern and secondary sputtering lithography can change the shape of
the ITO line pattern. Different shapes can control the direction and size of the
pretilt angle. This effect eliminates defects and reduces the response time.
PMID- 26418972
TI - Hodgkin lymphoma cell lines bind to platelets. Incubation with platelets induces
CD15 and P-selectin dependent adhesion of the cell lines to Human Umbilical Vein
Endothelial cells (HUVEC).
AB - Hodgkin's lymphoma is believed to spread in an orderly fashion within the
lymphatic compartment. In a minority of cases, after reaching the spleen, the
neoplasm disseminates, reminiscent of metastasis. In the spleen, the Hodgkin-Reed
Sternberg tumor cells come across platelets in the blood vessels and mainly in
the splenic red pulp. Based on this knowledge, we investigated the possibility of
platelets inducing cell adhesion in Hodgkin's lymphoma cell lines. We showed that
L428 and KMH-2 cells strongly adhere to thrombin-activated platelets. Cell
adhesion to platelets is partially dependent on CD15 antigens (Lewis(X)), mainly
sialyl-CD15, and P-selectin. KMH-2, as compared to L428 cells, showed increased
binding due to its differential high expression of the sialyl-CD15. As a
consequence of incubation with platelets, KMH-2 cells also produced increased
amounts of tumor necrosis factors alpha (TNFalpha) followed by enhanced binding
to human vascular endothelial cells (HUVEC). Incubation of both cell lines with
activated platelets also induced activation of AP-1 transcription complex. Our
findings are consistent with the concept that platelets play a critical role in
the dissemination of HRS cells in HL, predominantly in the spleen, by increasing
cell adhesion and thus promoting their proliferative and migratory properties
beyond the lymphatic system.
PMID- 26418974
TI - Self-Sealing and Puncture Resistant Breathable Membranes for Water-Evaporation
Applications.
AB - Breathable and waterproof membranes that self-seal damaged areas are prepared by
modifying a poly(ether ester) membrane with an amphiphilic polymer co-network.
The latter swells in water and the gel closes punctures. Damaged composite
membranes remain water tight up to pressures of at least 1.6 bar. This material
is useful for applications where water-vapor permeability, self-sealing
properties, and waterproofness are desired, as demonstrated for a medical cooling
device.
PMID- 26418975
TI - Tensions Between Policy and Practice in Finnish Biobank Legislation.
AB - In 2012 a new biobanking law came into effect in Finland which, according to
some, is one of the most comprehensive and broad national biobanking legislations
in the world to date. The law covers both clinical and research collections and
provides institutions with great flexibility in terms of transferring existing
collections into a biobank. The law also includes provisions for individuals
whose samples are stored in the biobank to request information regarding the
studies in which the sample has been used. However, this provision also compels
biobanks to provide an account of the significance of the research findings to
their individual health. This legal provision has created tension between policy
and practice in that most biobanks will struggle to interpret and apply this
provision in practice. The relationship between the rights and needs to conduct
research using biobank material and individual rights of access is sometimes
unclear and fraught with interpretational challenges. The derivation of national
interpretations of European Directives and Conventions gives rise to what I call
interpretive regulatory dissonance. This is expected to be a challenge for
harmonizing European and global biobanking activities in the future.
PMID- 26418976
TI - [Establishment of hemophilia A patient-specific inducible pluripotent stem cells
with urine cells].
AB - OBJECTIVE To generate hemophilia A (HA) patient-specific inducible pluripotent
stem cells (iPSCs) and induce endothelial differentiation. METHODS Tubular
epithelial cells were isolated and cultured from the urine of HA patients. The
iPSCs were generated by forced expression of Yamanaka factors (Oct4, Sox2, c-Myc
and Klf4) using retroviruses and characterized by cell morphology, pluripotent
marker staining and in vivo differentiation through teratoma formation. Induced
endothelial differentiation of the iPSCs was achieved with the OP9 cell co
culture method. RESULTS Patient-specific iPSCs were generated from urine cells of
the HA patients, which could be identified by cell morphology, pluripotent stem
cell surface marker staining and in vivo differentiation of three germ layers.
The teratoma experiment has confirmed that such cells could differentiate into
endothelial cells expressing the endothelial-specific markers CD144, CD31 and
vWF. CONCLUSION HA patient-specific iPSCs could be generated from urine cells and
can differentiate into endothelial cells. This has provided a new HA disease
modeling approach and may serve as an applicable autologous cell source for gene
correction and cell therapy studies for HA.
PMID- 26418977
TI - [Association of chromosome 17q copy number variation with overall survival of
patients with hepatocellular carcinoma and screening of potential target genes].
AB - OBJECTIVE To assess the association of copy number variations (CNVs) in
chromosome 17q with the overall survival(OS) of patients with hepatocellular
carcinoma(HCC), and to screen for target genes contained in the OS-related CNVs.
METHODS A total of 174 HCC cases were enrolled. For 66 patients, the follow-up
data was available. High-resolution Agilent Hu-244A array comparative genomic
hybridization (aCGH) and Affymetrix U133 Plus 2.0 expression arrays were used to
detect CNVs and gene expression of genes from the 17q region, respectively. The
association of CNVs and OS was assessed with Log-rank test, Kaplan-Meier survival
analysis, and Cox proportional hazards models. The gene expression in HCCs with
17q gain, HCCs without, and non-tumor liver tissues were compared with a Mann
Whitney U test. RESULTS Univariate association analysis showed that copy number
gain in 17q25.1-25.3 was significantly associated with reduced OS (Log-rank test,
P = 0.00002), and HCC cases with 17q25.1-25.3 gain had a 4.76-fold (95%CI: 2.31
9.81) increased hazard ratio (HR) for death from HCC, as compared to those
without the gain. Multivariate Cox proportional hazards regression model revealed
17q25.1-25.3 gain to be an independent prognostic marker for poor OS (HR = 3.17,
95%CI: 1.39-7.26, P = 0.006). The expression levels of 18 genes in 17q25.1-25.3
including SLC9A3R1, GRB2, and TK1 were significantly increased in HCCs with gain
than in those without (all P < 0.01) and non-tumor liver tissues (all P < 0.01).
CONCLUSION The association of 17q25.1-25.3 gain with reduced OS has indicated
that it is a prognostic marker for poor patient survival in HCC, for which
SLC9A3R1, GRB2, and TK1 are candidate genes.
PMID- 26418978
TI - [Drug resistance of colon cancer cells to 5-fluorouracil mediated by microRNA
21].
AB - OBJECTIVE To explore downstream regulatory pathway of microRNA-21 (miR-21) in
colon cancer cells (RKO) through detecting miR-21 and its target PDCD4, and the
influence of miR-21 regulation on the sensitivity of RKO cells to 5-fluorouracil
(5-FU). METHODS 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
(MTT) assay was used to determine the effect of 5-FU on the viability of RKO
cells with knockout of miR-21 or high expression of PDCD4. Real-time was used to
determine the expression of PDCD4, ABCC5 and CD44 in RKO cell after knockout of
miR-21. RESULTS MTT assay reveals that the IC50 of 5-FU in RKO-WT cells (52.82 +/
0.06 umol/L) was about 67% higher than in miR-21 knockout cells (32.23 +/- 0.05
umol/L) (P < 0.05), and the apoptosis ratio elevated after knockout of miR-21.
High expression of PDCD4, a target gene of miR-21, can negatively regulate the
expression of ABC transporter ABCC5 and the stem cell marker CD44. CONCLUSION MiR
21 can mediate the drug resistance to 5-FU by inhibiting its target PDCD4, which
can regulate the expression of ABCC5 and CD44 genes.
PMID- 26418979
TI - [Pathway-focused correlation study of genome-wide methylation status with visual
memory].
AB - OBJECTIVE To explore the biological processes and pathways associated with memory
function which may be regulated by gene promoter methylation. METHODS The genome
wide promoter methylation statuses in 9 healthy individuals were analyzed with a
Multiplex HG18 CpG Promoter chip. Genes with promoter methylation statuses
strongly correlated with both immediate and delayed visual memory function were
preceded for pathway and physical interactions analysis. RESULTS Sixty nine genes
have been correlated with both immediate and delayed visual memory functions.
Twenty two pathways, with a Q-value of < 0.05, were identified by the pathway and
physical interactions analysis, which included energy metabolism, axon guidance,
tyrosine kinase activity, anterograde synaptic vesicle transport, and leukocyte
migration and differentiation. CONCLUSION Pathways related with memory function
may be regulated by DNA methylation.
PMID- 26418980
TI - [Influence of genetic polymorphisms and non-genetic factors on the maintenance
dose of warfarin].
AB - OBJECTIVE To assess the influence of genetic polymorphisms and non-genetic
factors on warfarin maintenance dose variations in order to provide guidance for
personalized use of warfarin. METHODS Two hundred patients from outpatient and
inpatient with stable international normalized ratio(INR) were recruited.
Clinical data and blood samples were collected. Genotypes of 4 genes involved in
warfarin metabolic pathways were determined with Sanger sequencing. Based on
statistical analysis of warfarin maintenance dosage, a mathematical model was
established. RESULTS Among non-genetic factors, the age and height have
significant influence in warfarin dosage. The dosage is negatively correlated
with age but positively correlated with height. The difference in dosage for
between the 20-year-old group and 60-year-old group has reached 1.81 mg/day, and
that for between the 140 cm in height and 180 cm in height groups has reached
1.06 mg/day. VKORC1 -1639G/A, CYP2C9 430C/T, CYP2C9 1075A/C and CYP4F2 V433M
polymorphisms have significant influence on stable warfarin dosage. The dosage
for patients with wild type and mutant genotypes has varied from 0.35 mg/day to
0.84 mg/day. CONCLUSION Non-genetic factors and genetic polymorphisms play
important roles in personalized variations of warfarin maintenance dose. The
establishment of mathematical models considering multiple factors is helpful in
evaluating the safety and effectiveness of warfarin dosage.
PMID- 26418981
TI - [Application of quantitative fluorescence PCR for the prenatal diagnosis of
common fetal chromosomal aneuploidies].
AB - OBJECTIVE To assess the value of quantitative fluorescence PCR (QF-PCR) for the
prenatal diagnosis of common fetal chromosomal aneuploidies. METHODS A total of
2436 amniotic fluid samples were collected at 18 to 22 gestational weeks.
Multiplex QF-PCR was performed with fluorescence-labeled primers specific for 32
polymorphic short tandem repeat (STR) sites on chromosomes 21, 18, 13, X and Y.
The PCR products were assayed by capillary electrophoresis. All samples were also
assayed by karyotyping. RESULTS Seventy-six (3.12%) samples were diagnosed as
chromosomal aneuploidies by QF-PCR, among which 51 were trisomy 21, 12 were
trisomy 18, 2 were trisomy 13, and 1 was triploidy. The results were all
consistent with those of karyotyping. Ten samples were suspected as sex
chromosomal aneuploidies, among which 9 were confirmed, except for 1 case with X
structural abnormality. In addition, karyotyping has diagnosed 24 (0.99%) cases
of structural abnormalities, only one of which was suspected by QF-PCR with
partial abnormal STR results. Two (0.08%) samples were found to be mosaic by
karyotyping, one of which was suggested by QF-PCR with cut-off ratios of STR
markers. CONCLUSION QF-PCR is reliable for the diagnosis of numerical
abnormalities of chromosomes 21, 18, 13, X and Y. The method can serve as an
effective technique for rapid prenatal screening of common chromosome
aneuploidies in fetus.
PMID- 26418982
TI - [Bioinformatics analysis of differently expressed microRNAs in anxiety disorder].
AB - OBJECTIVE To identify differentially expressed microRNA (miRNA) in peripheral
blood mononuclear cells (PBMCs) of anxiety patients and predict their target
genes and function by bioinformatics analysis. METHODS The miRNA expression
profiles were determined using an Affymetrix array. To validate the results, real
time quantitative polymerase chain reaction (qRT-PCR) analysis in a larger cohort
was employed. The targets of the differentially expressed miRNAs were predicted
by Target Scan, miRBD, and DIANA-microT-CDS, and the results were analyzed by
gene ontology (GO) and KEGG pathway analysis using FunNet. RESULTS MicroRNA
microarray chip analysis has identified 7 miRNAs were detected with significant
changes in expression in PBMCs of anxiety patients. qRT-PCR analysis has
confirmed that the expression levels of 5 miRNAs (has-miR-4484, has-miR-4505, has
miR-4674, has-miR-501-3p and has-miR-663) were up-regulated. Intersecting the
genes by Target Scan, miRBD, and DIANA-microT-CDS has predicted 195 targets. GO
analysis showed that biological processes regulated by the predicted target genes
have included diverse terms. Some terms, e.g., nervous system development, nerve
growth factor receptor signaling pathway, neuron migration, dendrite development,
regulation of neuron projection development, midbrain development, regulation of
excitatory postsynaptic membrane potential, gliogenesis, dendrite morphogenesis,
etc. have direct relationship with the central nervous system and brain
functions. Pathway analysis showed that a significant enrichment in several
pathways related to neuronal brain functions such as glutamatergic synapse, axon
guidance, calcium signaling pathway, MAPK signaling pathway, GnRH signaling
pathway, Wnt signaling pathway, gap junction, long-term potentiation and VEGF
signaling pathway, etc. Among the five microRNAs, has-miR-4484, has-miR-4505, has
miR-4674 and has-miR-501-3p may have more important regulatory functions.
CONCLUSION Five miRNAs (has-miR-4484, has-miR-4505, has-miR-4674, has-miR-501-3p
and has-miR-663) are up-regulated in PBMCs of anxiety patients and may be closely
involved in the pathogenesis of anxiety disorder.
PMID- 26418983
TI - [Analysis of UPB1 gene mutation in a family affected with beta-ureidopropinoase
deficiency].
AB - OBJECTIVE To detect potential mutation in a Chinese family affected with beta
ureidopropinoase deficiency. METHODS Genomic DNA was extracted from peripheral
blood samples. All exons and flanking intron regions of the UPB1 gene were
amplified by PCR and detected by direct sequencing. RESULTS A homozygous mutation
c.977G>A was identified in exon 9 of the UPB1 gene in the proband. Both parents
of the proband had heterozygous change of the same site. CONCLUSION The c.977G>A
mutation of the UPB1 gene is responsible for the pathogenesis of the disease in
the infant.
PMID- 26418984
TI - [Polymorphisms of killer cell immunoglobulin-like receptor and its ligand HLA-I
gene among northern Chinese Han population].
AB - OBJECTIVE To investigate the distribution of killer cell immunoglobulin-like
receptors (KIR) and their specific ligands human leukocyte antigen-I (HLA-I) gene
in northern China. METHODS One hundred and eighty-four unrelated northern Chinese
Han individuals were recruited. Genotypes of the KIR and HLA-ABC genes were
studied by sequence-specific primer polymerase chain reaction (SSP-PCR). RESULTS
Sixteen KIR genes were detected among the 184 unrelated individuals. In all
individuals, the four framework genes were present. The frequencies for those
carrying the remaining 12 KIR genes have ranged from 16.3% to 99.5%. Twenty-four
KIR genotypes were identified, for which half were detected in a single
individual. A new genotype comprised of KIR2DL3, 3DL1, 2DP1 and the framework
genes was detected in one subject. Respectively, 12, 27 and 11 specificities of
HLA alleles were identified on the HLA-A, B, C loci. CONCLUSION The distribution
of polymorphisms of KIR and its ligand HLA-ABC genes among northern Chinese Han
population have been ascertained. The frequencies of 9 KIR/HLA combinations in
the above population have been determined for the first time.
PMID- 26418985
TI - [Genetic study of the Penta E locus and identification of rare alleles].
AB - OBJECTIVE To study the genetic polymorphisms of Penta E locus in Fujian Han
population. METHODS Polymorphisms of the Penta E locus in 851 unrelated
individuals were analyzed using polymerase chain reaction-short tandem repeat
(PCR-STR). The mutation rate of rare alleles was analyzed in 494 paternity
identification cases (in a total of 674 meiosis). RESULTS Twenty-six alleles were
identified for the Penta E locus, with their frequencies ranging from 0.0006 to
0.1528. There were 7 rare alleles, among which Penta E-28.4 ([AAAGA]29) was
identified for the first time. Genetic parameters of the Penta E locus in Fujian
Han population were obtained, including PIC= 0.91, PE= 0.817, PD= 0.986, and
mutation rate= 0.0015. CONCLUSION The Penta E locus is highly polymorphic and has
a low mutation rate in Fujian Han population. It also has a good prospect in
genetics applications. DNA sequencing is a good method for identifying rare
alleles.
PMID- 26418986
TI - [Molecular genetic study of a family featuring cardiac conduction block].
AB - OBJECTIVE To explore the genetic mechanism for a family affected with cardiac
conduction block. METHODS Affected family members were screened for potential
mutations of known candidate genes. As no pathogenic mutation was found, two
patients and one healthy member from the family were further analyzed by exomic
sequencing followed by Sanger sequencing. The pathogenicity of suspected mutation
was analyzed using bioinformatics software. RESULTS Sequencing of the full exome
has identified a c.G1725T mutation in the CLCA2 gene. Sanger sequencing has
detected the same mutation in all five patients, but not in the normal member
from the family. Bioinformatics analysis indicated that the mutation has resulted
in substitution of the 575th amino acid cysteine (C) by tryptophan (W). The site
is highly conserved and becomes pathogenic with the mutation. CONCLUSION The
heterozygous c.G1725T mutation in exon 11 of the CLCA2 gene probably underlies
the disease and fit the autosomal dominant pattern of inheritance.
PMID- 26418987
TI - [Congenital central hypoventilation syndrome: analysis of PHOX2B gene mutation in
a case].
AB - OBJECTIVE To report on the phenotype of an infant with central hypoventilation
syndrome (CCHS) and result of PHOX2B gene mutation analysis for the purpose of
genetic counseling and prenatal diagnosis. METHODS Clinical data of an infant
with CCHS was collected and analyzed. Potential mutation of PHOX2B gene was
analyzed by amplified fragment length polymorphism (amp-FLP) and DNA sequencing.
RESULTS The patient had typical clinical features of CCHS including frequent
hypoventilation during sleeping, hypoxemia and hypercapnia which could be
corrected by continuous ventilatory support. She also had repeated bruising and
was difficult-to-wean, but without any cardiac, pulmonary, neuromuscular or
brainstem lesions. DNA sequencing and amp-FLP of the PHOX2B gene showed that the
patient has carried a polyalanine expansion repeat mutation (PARM) in exon 3. A
27 bp duplication was confirmed in the repeat sequence of 20 alanines by cloned
and sequenced. This has led to an expansion of the repeat tract to 29 alanines.
The genotype was therefore 20/29. CONCLUSION A patient with CCHS has been
described. Mutation screening of PHOX2B gene can be used as an important support
for diagnosis and genetic counseling for such patients.
PMID- 26418989
TI - [Phenotypic and genetic analysis of a child featuring multiple malformations due
to chromosome 18p deletion].
AB - OBJECTIVE To analyze a neonate with multiple malformations and to correlate its
genotype with phenotype. METHODS The karotypes of the child and her parents were
subjected to G-banding chromosome analysis, and array comparative genomic
hybridization (array-CGH) was used for fine mapping of the aberrant region.
RESULTS The karyotype of the child was ascertained as 46,XX,del(18)(p11.2). Array
CGH has identified a 9.8 Mb deletion at 18p11.32-p11.22. The patient has
presented features such as holoprosencephaly, choanal atresia, heart defect, and
craniofacial dysmorphisms. CONCLUSION The de novo 18p deletion probably underlies
the main clinical manifestations of the child.
PMID- 26418988
TI - [Phenotypic and genetic analysis of a child with blepharophimosis, ptosis,
epicanthus inverses syndrome and tetralogy of Fallot].
AB - OBJECTIVE To determine the genetic cause of a child with blepharophimosis,
ptosis, and epicanthus inverses syndrome and tetralogy of Fallot, and to
correlate the phenotype with the genotype. METHODS Routine G-banding has been
previously performed on the patient and her parents. Chromosome microarray
analysis (CMA) was performed for the three individuals and the fetus. RESULTS
Chromosomal analysis has suggested normal karyotypes for the child and her
parents. However, a de novo 8.9 Mb deletion on chromosome 3q22.1-q23 was detected
by CMA. The deleted region has encompassed 74 genes including 41 disease-related
genes, and this is also the most frequent region involved in interstitial 3q
deletion. Patients with deletion of this region often have a common feature of
dysplasia of eyelids, as well as a spectrum of other anomalies according to
different breakpoints, including microcephaly, skeletal anomalies, congenital
heart defects, cranial anomalies, intellectual disability and developmental
delay. The patient's phenotype was in accordance with such spectrum. Her parents
and sib did not show this variation by CMA. CONCLUSION The de novo interstitial
deletion of 3q22.1-q23 probably underlies the main clinical manifestation in this
child. CMA can provide more detailed information and allow further investigation
of the genotype-phenotype correlation.
PMID- 26418990
TI - [Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia with P53 deletion and
TCR-delta rearrangement in a case].
AB - OBJECTIVE To study the morphology, immunology, cyto- and molecular genetics of a
patient with lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM),
deletion of P53 gene and rearrangement of clonal T cell receptors-delta (TCR
delta) gene. METHODS The cell morphology and immunocytochemistry were analyzed by
bone marrow testing and biopsy. Cellular immunology was analyzed by flow
cytometry. Genetic analysis was carried out by chromosome karyotyping,
fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR).
Immunoglobulin M (IgM) in serum and urine was assayed by immunofixation
electrophoresis. And the effect of chlorambucil therapy was evaluated. RESULTS
Bone marrow biopsy suggested that the patient was of B lymphocyte type and had
abnormal increase of lymphocytoid plasma cells, which were CD38 and CD138
positive. The patient had a normal male karyotype. FISH and PCR analysis of
peripheral blood samples suggested deletion of P53 gene and rearrangement of TCR
delta gene. Immunofixation electrophoresis has detected IgM-kappa in both serum
and urine. The patient showed partial response to chlorambucil. CONCLUSION In
addition to typical clinical features, bone marrow examination, flow cytometry,
histochemistry and immunophenotyping, testing for P53 gene deletion and
lymphocyte gene rearrangement can facilitate the diagnosis and treatment of
LPL/WM.
PMID- 26418991
TI - [8p11 myeloproliferative syndrome with CEP110-FGFR1 fusion in a patient].
AB - OBJECTIVE To explore the clinical and laboratory features of a patient with 8p11
myeloproliferative syndrome (EMS) and CEP110-FGFR1 fusion. METHODS Combined bone
marrow cytology, fluorescence in situ hybridization, fusion gene detection was
used to analyze the patient. RESULTS Clinically, the patient had many features
similar to those with chronic myelomonocytic leukemia, which included
hyperleukocytosis, marked eosinophilia, monocytosis, myeloid hyperplasia and
hyperplasia. Fluorescence in situ hybridization analysis for FGFR1 gene
rearrangement was positive. Further study of the mRNA also confirmed an in-frame
fusion between exon 38 of the CEP110 gene and exon 9 of FGFR1 gene. CONCLUSION
EMS with CEP110-FGFR1 fusion is a very rare and distinct myeloproliferative
neoplasm. FISH and molecular studies may improve its diagnosis.
PMID- 26418992
TI - [Application of multiplex ligation-dependent probe amplification technique in
prenatal diagnosis of alpha-thalassemia].
AB - OBJECTIVE To assess the application value of multiplex ligation-dependent probe
amplification (MLPA) for the detection of gene deletion and prenatal diagnosis of
alpha-thalassemia. METHODS MLPA was applied for 2 cases with alpha-thalassemia
phenotype by whole blood cell counting and hemoglobin component detection but
were ruled out by regular molecular diagnosis. Potential gene deletions and point
mutations of alpha-thalassemia gene were detected with regular Gap-polymerase
chain reaction (Gap-PCR) and reverse dot blotting (RDB) in 89 cases where one or
both partners were carriers of alpha-thalassemia mutations. Meanwhile, MLPA was
used for detecting alpha-globin gene deletion among the 89 samples. RESULTS For
the 2 cases with alpha-thalassemia phenotype, no alpha globin gene deletion was
detected by MLPA, but were subsequently confirmed as iron-deficiency anemia. The
results of MLPA and Gap-PCR detection for the 88 cases were consistent, except
for 1 fetal sample (chorionic villi) which could not be diagnosed by Gap-PCR and
was confirmed to be - SEA/alphaalpha by MLPA. CONCLUSION MLPA can be applied to
prenatal diagnosis of alpha-thalassemia as an effective supplement to Gap-PCR to
reduce both misdiagnosis and missed diagnosis and improve the accuracy of
prenatal diagnosis.
PMID- 26418993
TI - [Genetic analysis and prenatal diagnosis of Xp deletion in a family with
Duchenne/Becker muscular dystrophy].
AB - OBJECTIVE To delineate a deletional mutation of the Dystrophin gene on the short
arm of chromosome X in a family affected with Duchenne/Becker muscular dystrophy.
METHODS G-banded karyotyping, multiple ligation probe amplification (MLPA), array
based comparative genomic hybridization(array-CGH) and whole genome exon high
throughput sequencing were employed to delineate the mutation in the family.
RESULTS GTG banding has demonstrated deletion of the terminal part of the short
arm of chromosome X in the fetus. The same deletion was also found in its mother
and maternal grandmother. MLPA analysis has revealed removal of exons 52 to 79 of
the Dystrophin gene. A 30 Mb deletion in Xp22.33-p21.1 and a 10 Mb duplication in
Xq27.2-q28 were identified by array-CGH and whole genome exon high-throughput
sequencing. CONCLUSION The Xp deletion has led to deletion of exons 52 to 79 of
the Dystrophin gene in the family. The female carriers also had certain features
of Turner syndrome due to the same deletion.
PMID- 26418994
TI - [Prenatal diagnosis of five cases of monochorionic-diamniotic twins discordant
for karyotype analysis].
AB - OBJECTIVE To explore the mechanism and diagnostic method for monochorionic
diamniotic twins discordant for karyotype analysis. METHODS Dual amniocentesis
was performed on five pairs of monochorionic-diamniotic twins, which all
consisted of a normal twin and one with multiple malformations revealed by
ultrasound. Karyotype analysis was performed on amniocytes derived from each of
the twins. Zygosity was also determined with DNA extracted from amniocytes with
16 polymorphic microsatellite markers. RESULTS Three cases of 45,X, one case of
47,XX,+9 and one case of 47,XY,+18 were detected among the abnormal twins, while
the normal fetuses all had a normal karyotype. DNA analysis suggested that, in
all cases, the twins have shared the 16 polymorphic microsatellite markers, which
confirmed their monozygosity. CONCLUSION Monochorionic-diamniotic twins may be
discordant for karyotyping, for which anaphase lagging, chromosomal non
disjunction and trisomy rescue may be the underlying reasons. As a simple method,
dual amniocentesis can be used to obtain amniotic fluid samples for karyotype
analysis and determination of zygosity for such twins.
PMID- 26418995
TI - [Molecular mechanism of 101A>G and 845G>A mutations of RHD gene responsible for a
weak RhD].
AB - OBJECTIVE: To explore the molecular basis for an individual with a rare weak D
phenotype. METHODS: Regular serological assaying and indirect antiglobulin
testing (IAT) were performed to characterize the RhD blood group. Mutations of
the RHD gene were screened by polymerase chain reaction (PCR), reverse
transcription PCR and DNA sequencing. Amplified cDNA product was TA cloned and
subjected to haplotype analysis. RESULTS: The RhD blood group of the proband was
determined as weak D. The result of PCR amplification showed that all of the 10
exons of the RHD gene were present. Heterozygote status of 101A/G and 845A/G were
determined by gDNA and cDNA sequencing. After TA cloning and haplotype
sequencing, two alleles 101A>G mutation (weak D 101G ) and 845G>A mutation (weak
D type 15) were revealed. CONCLUSION: 101A>G and 845G>A mutations are responsible
for the low expression of RhD antigen on the red blood cells of the proband,
which has resulted in a weak D phenotype.
PMID- 26418996
TI - [Study of molecular mechanism for a blood sample with A3 phenotype].
AB - OBJECTIVE To explore the molecular mechanism for a blood sample with mixed-field
hemagglutination upon determination of ABO blood group. METHODS Serological
techniques were employed to identify the erythrocyte phenotype. The A and B
antigens were detected by flow cytometry. The preliminary genotype of ABO gene
was assayed with sequence-specific primer-polymerase chain reaction (PCR-SSP).
Exons 6 and 7 of the ABO gene were amplified with PCR and analyzed by direct
sequencing. Haplotypes of the ABO gene were analyzed by cloning sequencing as
well. RESULTS The serological reaction pattern has supported an O phenotype when
all the tubes were centrifuged for the first time. However, a mixed-field
hemagglutination of red blood cells (RBCs) with anti-A antibodies was present
after the tube was centrifuged five times later. A antigens were detected on the
surface of partial red blood cells of the sample by flow cytometry. PCR- SSP
results have shown that the preliminary ABO genotype was A/O. Analysis of the
fragments of exons 6 and 7 of the ABO gene has indicated that heterozygosis lied
as follows: 261G/A, 425T/T, 467C/T, 646A/T, 681A/G, 745C/T, 771C/T, 829A/G,
conjecturing the genotype to be A307/O02, which was confirmed by haplotype
sequence analysis. Compared with A101 allele, A307 allele has two missense
mutations, 467C> T and 745C> T, which have resulted in substitutions Pro156Leu
and Arg249Trp in the A glycosyltransferase polypeptide chain. CONCLUSION A
variant allele (A307) has been identified for the first time in mainland China,
which is responsible for the formation of A3 phenotype.
PMID- 26418997
TI - [Association of TNF-alpha and IL-13 genes polymorphisms with bronchial asthma].
AB - OBJECTIVE To assess the association of polymorphisms of TNF-alpha gene
(rs1799724, rs1800630, rs1799964 and rs769178) and IL-13 gene (rs2158177 and
rs1295687) with susceptibility to asthma among ethnic Chinese in Qingdao region.
METHODS For 400 asthma patients and 200 healthy subjects, above polymorphisms
were detected with a SNaPshot method. RESULTS For rs2158177, the frequency of
genotype of GG in the asthma group was significantly lower than the control group
(2.8% vs. 5%, OR = 0.31, 95%CI: 0.12-0.82, P = 0.021). No significant difference
was detected in the genotypic frequencies for the remaining 5 polymorphisms
between the two groups (All P > 0.05). CONCLUSION The study has indicated that
rs2158177 polymorphism of the IL-13 gene is associated with asthma in ethnic Han
Chinese from Qingdao. No association has been found between polymorphisms of TNF
alpha gene with susceptibility to asthma.
PMID- 26418998
TI - [Association of single nucleotide polymorphisms of susceptibility genes of type 2
diabetes mellitus with liability to gout among ethnic Han Chinese males from
coastal region of Shandong].
AB - OBJECTIVE To assess the association of single nucleotide polymorphisms (SNPs) of
susceptibility genes of type 2 diabetes mellitus (T2DM) with liability to gout
among ethnic Han Chinese males from coastal region of Shandong province. METHODS
Seven SNPs within the susceptibility genes of T2DM, including rs10773971(G/C) and
rs4766398(G/C) of WNT5B gene, rs10225163(G/C) of JAZF1 gene, rs2069590(T/A) of
BDKRB2 gene, rs5745709(G/A) of HGF gene, rs1991914(C/A) of OTOP1 gene and
rs2236479(G/A) of COL18A1 gene, were typed with a custom-made Illumina GoldenGate
Genotyping assay in 480 male patients with gout and 480 male controls. Potential
association was assessed with the chi-square test. RESULTS No significant
difference was detected for the 7 selected SNPs in terms of genotypic and allelic
frequencies (P > 0.05). When age and body mass index (BMI) were adjusted, the 7
genetic variants still showed no significant association with gout. CONCLUSION
The genotypes of the 7 selected SNPs are not associated with gout in ethnic Han
Chinese male patients from the coastal region of Shandong province. However, the
results need to be replicated in larger sets of patients collected from other
regions and populations.
PMID- 26418999
TI - [Associations of Crohn's disease with DR4 and DR5 gene polymorphisms].
AB - OBJECTIVE: To assess the associations of death receptor DR4 and DR5 gene
polymorphisms with Crohn's disease (CD). METHODS: A total of 295 CD patients and
490 healthy controls were recruited. Three single nucleotide polymorphisms (SNPs)
of the DR4 (rs13278062, rs20575) and DR5 (rs1047266) genes were determined with a
SNaPshot method. Unconditional logistic regression analysis was carried out for
determining the allelic and genotypic differences of the three SNPs between CD
patients and the controls, as well as the influence of the DR4 and DR5 gene
polymorphisms on the clinical features of CD patients. Linkage disequilibrium and
haplotype analysis were calculated by haplotype 4.2 and R language software. A
gene-gene interaction model was established to analyze whether the three SNPs can
exert a synergistic effect on the susceptibility to CD. RESULTS: The mutant
allele (T) and genotype (GT+TT) of DR4 (rs13278062) were increased among CD
patients compared to the controls (37.12% vs. 32.04%, P = 0.040, 95%CI: 1.010
1.550; 62.71% vs. 54.90%, P = 0.032, 95%CI: 1.028-1.855, respectively). However,
the allelic and genotypic frequencies of DR4 (rs20575) and DR5 (rs1047266) did
not differ between the two groups (all P > 0.05). Based on the Montreal
Classification Standards, the CD patients were stratified by locations and
behaviors of the disease. After multiple comparison correction (P < 0.0125),
compared to ileocolonic CD patients respectively, the mutant allele (T) and
genotype (GT+TT) of the rs13278062 polymorphism were significantly increased in
colonic CD patients (41.04% vs. 25.64%, P = 0.002, 95%CI: 0.315-0.778; 66.04% vs.
41.03%, P = 0.001, 95%CI: 0.196-0.655, respectively) and terminal ileum CD
patients (41.44% vs. 25.64%, P = 0.002, 95%CI: 0.311-0.762; 74.77% vs. 41.03%, P
< 0.001, 95%CI: 0.126-0.437, respectively). In comparison to penetrating CD
patients, the mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were
significantly decreased in stricturing CD patients (32.29% vs. 48.91%, P = 0.007,
95%CI: 0.300-0.828; 57.29% vs. 86.96%, P = 0.001, 95%CI: 0.078-0.520,
respectively). A similar conclusion was drawn for the mutant genotype (GT+TT) of
DR4 (rs13278062) in non-stricturing, non-penetrating CD patients (58.82% vs.
86.96%, P = 0.001, 95%CI: 0.086-0.536). Haplotype analysis indicated that the CT
haplotype formed by rs20575 and rs13278062 was increased in CD patients compared
to the controls (37.1% vs. 31.8%, P = 0.029, OR=1.279, 95%CI: 1.022-1.600). The
outcome of a gene-gene interaction model indicated that the mutant genotype
(GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5 (rs1047266) may
play a negatively synergistic role in CD patients (B = - 0.483, OR = 0.617, P =
0.030). CONCLUSION: The rs13278062 polymorphism of the DR4 gene not only can
confer an increased risk for CD, but may also influence the location of the
lesions and the disease behaviors. The CT haplotype formed by rs20575 and
rs13278062 may be an independent risk factor for CD. Furthermore, the mutant
genotype (GT+TT) of DR4 (rs13278062) and mutant genotype (CT+TT) of DR5
(rs1047266) may exert a negative synergistic effect on CD.
PMID- 26419000
TI - [Advances in research of SCARB2 functions and related disorders].
AB - SCARB2 (scavenger receptor class B, member 2) is a lysosomal membrane
glucoprotein, which is encoded by SCARB2 gene. It takes vital parts in the
physiological and pathological processes including the transportation of beta
glucocerebrosidase to the lysosome, infection of EV71 and load-induced cardiac
myocyte hypertrophy. This article has reviewed the molecular structure and
functions of SCARB2 gene and its protein, as well as their relationship with
diseases.
PMID- 26419001
TI - [Progress of molecular genetics research on rheumatoid arthritis].
AB - Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disorder that
principally attacks flexible joints and synovia. The precise pathogenesis of RA
remains unclear, and genetic factors probably play an important role in its
etiology. In addition to genes from human leukocyte antigen (HLA) region, such as
HLA-DRB, genes from non-HLA region, such as TIM-3, PTPN22, TRAF1/C5, STAT4, CCR5,
PADI4 and FCGR2A may also contribute to its susceptibility. The advance in
molecular genetics research on RA is reviewed here.
PMID- 26419002
TI - [Progress in research on imprinted gene associated with male infertility].
AB - The connection between male infertility and abnormal methylation of imprinted
genes has attracted much attention. Some imprinted genes, e.g., H19, MEG3, MEST
and SNRPN, are known to be related with male infertility. Abnormal imprinted
information may influence sperm concentration, motility and morphology, but the
mechanism is still unclear. Sperm genomic imprinting reconstruction and erase
respectively occur at the time of spermatogenesis and before embryo transfer.
Many studies have shown that the probability of imprinting disorder syndrome of
offspring born through assisted reproductive technology (ART) was significantly
higher, leading to the worry about the safety of ART and speculation that the
operation and in vitro environment may affect sperm imprinted information, which
in turn may lead to imprinting diseases in the offspring. However, above
connection still lacks convincing evidence. This paper has conducted a literature
review of recent literature and explored the impact of abnormal methylation of
imprinted genes on male fertility and the offspring.
PMID- 26419003
TI - [Infantile spastic paraplegia in two cases from a pedigree].
PMID- 26419004
TI - [A pedigree affected with Huntington disease].
PMID- 26419005
TI - [A pedigree affected with congenital polydactyly].
PMID- 26419006
TI - Thermal Pretreatment Improves Viability of Cryopreserved Human Endothelial Cells.
AB - A high survival rate of cryopreserved cells requires optimal cooling and thawing
rates in the presence of a cryoprotective agent (CPA) or a combination of CPAs in
adequate concentrations. One of the most widely used CPAs, dimethyl sulfoxide
(Me2SO), however is toxic at high concentrations and has detrimental effects on
cellular functions. Additional processing steps are necessary to remove the CPA
after thawing, which make the process expensive and time consuming. Therefore it
is of great interest to develop new cryoprotective strategies to replace the
currently used CPAs or to reduce their concentration. The aim of this study was
to investigate if thermal activation of human pulmonary microvascular endothelial
cells (HPMEC ST-1.6R), prior to cryopreservation, could improve their post-thaw
viability since the resulting heat shock protein expression acts as an intrinsic
cellular protection mechanism. The results of this study suggest that both heat
and cold shock pretreatments improve cryopreservation outcome of the HPMEC ST
1.6R cells. By re-cultivating cells after heat shock treatment before
cryopreservation, a significant increase in cellular membrane integrity and
adherence capacity could be achieved. However a combination of thermal activation
and cryopreservation with alternative CPAs such as ectoine and L-proline could
not further enhance the cell viability. The results of this study showed that
pretreatment of endothelial cells with thermal activation could be used to reduce
the Me2SO concentration required in order to preserve cell viability after
cryopreservation.
PMID- 26419007
TI - Adolescents' emotional engagement in friends' problems and joys: Associations of
empathetic distress and empathetic joy with friendship quality, depression, and
anxiety.
AB - Although empathetic distress (i.e., taking on a friend's emotional distress as
one's own) has been examined as a "cost of caring" especially common among girls,
relations with adjustment remain untested. The current study tested associations
of empathetic distress with friendship quality, depression, and anxiety.
Adolescents (N = 300, ages 12-18) reported on their perceived experience of
empathetic distress following a conversation with a friend about problems. The
study also considered youths' emotional engagement in friends' positive life
events, referred to as empathetic joy. Results indicated that girls reported
greater empathetic distress and empathetic joy compared with boys. Findings also
suggest that although empathetic distress may have positive implications for
youths' friendship adjustment, this may come at the expense of emotional well
being. In contrast, empathetic joy was associated with greater positive
friendship quality and fewer internalizing symptoms.
PMID- 26419008
TI - Intravitreal ranibizumab for choroidal neovascularization secondary to gyrate
atrophy in a young patient: a multimodal imaging analysis.
AB - PURPOSE: To present a case of choroidal neovascularization (CNV) due to gyrate
atrophy (GA) treated with intravitreal ranibizumab. METHODS: A 35-year-old man
presented with sudden loss of vision and central scotoma in the right eye, as
well as progressive night vision deterioration over the past several years in
both eyes. His best-corrected visual acuity (BCVA) was 6/60 in the right eye and
6/5 in the left eye. Funduscopy revealed bilateral confluent areas of
chorioretinal atrophy and optical coherence tomography showed subretinal fluid
consistent with CNV development in the right eye, which was confirmed by fundus
fluorescein angiography (FFA) and indocyanine green angiography (ICGA). The left
eye was normal. The patient had a family history of GA. Elevated levels of plasma
ornithine were detected, establishing the diagnosis. RESULTS: The patient
received a regimen of 3 monthly off-label intravitreal ranibizumab injections in
the right eye. At the 6-month follow-up, no subretinal fluid was noticed and BCVA
was 6/48. No other injections were performed, but the patient was advised to
start an arginine-restricted diet and take vitamin B6 (pyridoxine) 300 mg daily.
The BCVA was preserved and chorioretinal atrophy had not progressed on
funduscopy, FFA, or ICGA 1 year later. CONCLUSIONS: Intravitreal ranibizumab can
offer promising anatomical and functional results, maintaining visual acuity in
patients with CNV secondary to GA, especially if used in combination with
arginine-restricted diet and vitamin B6 supplementation.
PMID- 26419009
TI - [Progress on biotherapy of hepatocellular carcinoma].
PMID- 26419010
TI - [Advances in gene therapy of liver cancer].
PMID- 26419011
TI - [Logistic regression analysis of risk factors of hepatogenous diabetes in
patients with liver cirrhosis].
PMID- 26419012
TI - [Congenital hepatic fibrosis with polycystic kidney diseases: case report].
PMID- 26419013
TI - [Primary hepatic amyloidosis with gastrointestinal bleeding: case report].
PMID- 26419014
TI - [Current status of clinical applications of the artificial liver support system].
PMID- 26419015
TI - [Recent progress in identifying and characterizing factors influencing the
natural history of chronic hepatitis C].
PMID- 26419016
TI - [Advances in understanding the role of microRNA-regulated hepatitis B virus X
protein in the pathogenesis of hepatitis B virus-induced hepatocellular
carcinoma].
PMID- 26419017
TI - [6 goals and 6 procedures for reducing mercury load caused by amalgam - a plea
for a national exit plan].
PMID- 26419018
TI - [The goals and responsibilities of "Military Medicine Evenings"].
PMID- 26419019
TI - [100 years ago].
PMID- 26419020
TI - Proceedings of the 24th International Information Processing in Medical Imaging
Conference, IPMI 2015, June 28-July 3, 2015, Isle of Skye, United Kingdom.
PMID- 26419021
TI - Missouri Medicine 2015 member guide and directory.
PMID- 26419022
TI - [THE STATE OF HEPATIC AND SPLANCHNIC BLOOD FLOW IN VARIOUS TYPES OF COMPLICATED
PANCREATIC PSEUDOCYSTS].
AB - Investigations were conducted in 37 patients, suffering complicated pancreatic
pseudocysts. In accordance to data of ultrasound Doppler flowmetry for the blood
flow along portal vein, a. hepatis communis, a. mesenterica superior in
complicated pancreatic pseudocysts compensatory--adaptive reactions on level of
hepatic--spanchnic blood flow are directed towards restriction of the blood
inflow through the portal vein system. This is accompanied by the common
peripheral vascular resistence raising in basin of a. mesenterica superior, which
have depended upon the patients' state severity, caused by reduction of the
volume blood flow in a certan vascular collector. The oxygen debt of the liver in
these patients is compensated by the volume blood flow enhancement along a.
hepatis communis.
PMID- 26419023
TI - [ROLE OF MICROFLORA OF THE ABDOMINAL CAVITY EXUDATE IN THE ENDOGENIC INTOXICATION
OCCURRENCE IN PATIENTS, SUFFERING COMPLICATED ACUTE CHOLECYSTITIS WITH CONCURRENT
CARDIAC INSUFFICIENCY OF ISCHEMIC GENESIS].
AB - While complicated acute cholecystitis (ACH) course the focus of infection
constitutes one of the main causes of the endogenic intoxication (EI) occurrence,
what leads to ischemic and hypoxic myocardial damage. There were presented the
treatment results analysis in 213 patients, ageing 60 years old and older,
managed for an ACH, complicated by peritonitis, paravesical abscess, with
concurrent cardiac insufficiency of ischemic genesis, to whom laparoscopic
cholecytectomy (LCHE) was conducted. Microflora of the abdominal cavity exudates
in the patients, suffering an ACH of various severity, was studied. More rapid
regression of inflammatory process, the EI severity and the ischemic-hypoxic
myocardial affection reduction, positive impact on hemodynamics, reduction of
myocardial ischemia severity were noted while local affection, when
bacteriophages for treatment were applied.
PMID- 26419024
TI - [DISSEMINATION BY H. PYLORI IN PATIENTS, SUFFERING VARIOUS FORMS OF
CHOLECYSTITIS].
AB - Comparative analysis of dissemination by H. pylori of the bile portions in
patients of a control group, suffering an acute calculous cholecystitis (ACCH),
was performed. Dissemination of H. pylori in a control group was significantly
less, than in a bile portions of patients, suffering ACCH. While analyzing the
rate and degree of dissemination by H. pylori of the gastic and gallbladder
mucosa biopsies of patients, suffering chronic non-calculous cholecystitis,
associated with duodenogastric reflux and gastroduodenitis, bacteria were
revealed trustworthy more often and in more number, than in a gallbladder mucosa
in patients, suffering ACCH.
PMID- 26419025
TI - [MINIINVASIVE TECHNOLOGIES IN TREATMENT OF POSTOPERATIVE ABDOMINAL HERNIAS].
AB - Methods and results of treatment of 119 patients, suffering postoperative
abdominal hernia, were analyzed. There was established, that application of
laparoscopic miniinvasive technologies permits to improve the results of
treatment in patients in comparison with those after open operative
interventions, due to shortening of the operation duration, better visualization
during viscerolysis conduction, shortening of rehabilitation period, the patients
postoperative quality of life improvement.
PMID- 26419026
TI - [APPLICATION OF FISTULA PLUG WITH THE FIBRIN ADHESIVE IN TREATMENT OF RECTAL
FISTULAS].
AB - Results of surgical treatment of 21 patients, suffering high transsphincteric and
extrasphincteric rectal fistulas, were studied. In patients of Group I the
fistula passage was closed, using fistula plug obturator; and in patients of
Group II--by the same, but preprocessed by fibrin adhesive. The fistula aperture
germeticity, prophylaxis of rude cicatrices development in operative wound zone,
promotion of better fixation of bioplastic material were guaranteed, using
fistula plug obturator with preprocessing, using fibrin adhesive.
PMID- 26419027
TI - [PREDICTING FACTORS OF THE LIFE SPAN IN PATIENTS, SUFFERING METASTATIC COLORECTAL
CANCER AND SYNCHRONOUS HEPATIC AFFECTION AFTER SURGICAL TREATMENT].
AB - The results of treatment of 125 patients, suffering metastatic hepatic affection
in colorectal cancer (pT1--4N0--2M1--in colonic cancer and pT1--3N0--2M1--in
cancer recti), to whom in 2008-2015 yrs a one-staged (Group 1) or two-staged
(Group II) surgical treatment was done. In affection of 4 regional lymph nodes
and more (pN2) late results were less favorable, than in pN1 or pN0, not
depending from surgical approach choosed. In 48 (38.4%) patients with one
syndromal hepatic metastatic focus, the indices of general three-year and five
year cumulative survival were the best, than in other groups--82 and 63% (p =
0.001) accordingly; in monolobar affection--68 and 49%, and in bilobar--23 and
0%, not depending from method of surgical treatment (p < 0.001) choosed.
Predictive factors were established, which impact negatively the indices of
general survival in patients, suffering metastatic hepatic affection in
colorectal cancer: hepatic metastatic foci number 4 and more, bilobar hepatic
metastatic affection.
PMID- 26419028
TI - [LAPAROSCOPIC HERNIOPLASTY IN INCARCERATED INGUINAL HERNIAS].
AB - The results of laparoscopic hernioplasty, using TAPP method and operation of
Lichtenstein in 80 patients, suffering incarcerated inguinal hernia, were
analyzed. While achievement of similar good and excellent immediate and late
results, laparoscopic procedure has several advantages and may be used as a
method of choice for treatment of inguinal hernia.
PMID- 26419029
TI - [MORPHOMETRIC AND HISTOLOGICAL CHANGES OF TISSUES IN PATIENTS, WHO UNDERWENT
OPERATIONS FOR POSTOPERATIVE ABDOMINAL HERNIAS].
AB - The impact of hernioplasty on postoperative morphometric and histological changes
in tissues of patients, suffering postoperative abdominal hernias (POAH), was
studied. For POAH 135 patients were operated, in 85 of them (the main group)-
combined methods of hernial gate plasty in accordance to procedures proposed, and
in 50 (control group)--classical methods of hernial gate were applied. The most
favorable course of the wound process of the inflammatory, changes reduction and
stabilization of the tissues reaction on implant already on the 7th postoperative
day was noted after application of a sub lay method in original modification.
PMID- 26419030
TI - [LONGITUDINAL SEGMENTAL SHIFT OF THE LEFT VENTRICULUS WALLS IN PATIENTS,
SUFFERING THE AORTAL VALVE STENOSIS].
AB - In patients, suffering the aortal valve (AV) stenosis, the shift of middle and
apical parts of all left ventriculus (LV) walls and basal parts of anterior-
septa, anterior, posterior and inferior walls almost do not differ from those in
norm. The shift of basal parts of inferior--septal and lateral walls had a
tendency for lowering in comparison with such in norm. It is possible, that this
phenomenon of the initial lowering of the movement amplitude in basal parts of
inferior--septa and lateral walls of LV in patients, suffering the AV stenosis
with preserved fraction of ejection, precedes to disorders of its hemodynamics
and constitutes a predictor of the heart ejection reduction. So far, early
revealing of the LV dysfunction play an important role in determination of terms
of the operative intervention conduction in patients, suffering the AV stenosis.
PMID- 26419031
TI - [NEGATIVE IMPACT OF CHROMOSOME 22Q11 MICRODELETION ON RESULTS OF TREATMENT IN
PATIENTS, SUFFERING CONONTRUNCAL FAILURES OF HEART AND MAIN AORTO-PULMONARY
COLLATERAL ARTERIES].
AB - Dependence of results of surgical treatment in 42 patients, suffering conotruncal
failures and main aorto-pulmonary collateral arteries from presence of the
chromosome 22q11 deletion syndrome, was analyzed. While presence of the
chromosome 22q11 deletion syndrome duration of treatment of patients in intensive
therapy unit and artificial pulmonary ventilation are longer, pressure in a
pulmonary artery system after radical operative failures correction is higher,
general lethality is bigger, than while the chromosome 22q11 deletion syndrome
absence. The data obtained must be taken into account while determining tactics
of treatment in patients with confirmed diagnosis of the chromosome 22q11
deletion syndrome.
PMID- 26419032
TI - [SURGICAL TECHNIQUE OF A RENAL ARTERY CONTROL WHILE REMOVAL OF TUMORAL THROMBI
FROM VENA CAVA INFERIOR].
AB - Efficacy and safety of a renal artery ligation after thrombectomy in comparison
with those while using a standard surgical technique were studied. Possibility of
performance and safety of thrombectomy without preliminary ligation of renal
artery was proved. The results did not depend on level of intravenous tumoral
spread and were significantly better, than while application of standard
approaches to renal artery because of absence of embolic complications.
PMID- 26419033
TI - [EXPERIENCE OF APPLICATION OF THE GENE INDUCTOR OF VASCULAR ENDOTHELIUM GROWTH
FACTOR IN TREATMENT OF PATIENTS, SUFFERING ATHEROSCLEROTIC ISCHEMIA OF THE LOWER
EXTREMITIES TISSUES].
AB - The results of examination of patients, suffering chronic ischemia of the lower
extremities (LE) stages IIB - III (according to Fontaine), in whom preparation
Neovasculgen was used in complex of medicinal therapy, were presented. In terms
of follow-up before 12 months the distance, which the patients passed before the
pain occurrence, have enhanced by 92.2%, and the ankle-brachial index--by 30.9%.
Complications while application of the preparation were absent. Due to the
treatment conducted there were LE saved and the patients' quality of life
improved.
PMID- 26419034
TI - [THE CHOICE OF SURGICAL TREATMENT METHOD FOR THE DEEP VEINS THROMBOSIS IN SYSTEM
OF VENA CAVA INFERIOR].
AB - There were analyzed the results of examination and treatment of 455 patients,
suffering deep veins thrombosis in a system of vena cava inferior, of whom 175
(38.5%) were operated on. Inclusion of ultrasound duplex scanning,
roentgencontrast phlebography, multispiral computer tomography with intravenous
contrasting, radionuclide phleboscintigraphy into complex of clinic-instrumental
examination of the patients gives possibility to estimate the disorders of the
main trunk and collateral venous blood flow in the deep veins thrombosis, as well
as to substantiate indications and choice of the operative treatment method.
PMID- 26419035
TI - [EFFICACY OF SURGICAL TREATMENT OF VARICOSE DISEASE, DEPENDING ON ADSORPTION
RHEOLOGIC PROPERTIES OF BLOOD].
AB - Physico-chemical adsorption-rheological properties of venous blood in patients,
suffering varicose disease of the lower extremities, and their impact on efficacy
of various methods of surgical treatment were studied. Conduction of endovasal
laser coagulation in combination with crossectomy have promoted enhancement of
operative treatment efficacy in patients in initial terms of observation (in 1
week), in 1 month a complete occlusion of the vein was noted more rarely.
Efficacy of a small--power laser ablation with irradiation power of 10 W and less
in 4 weeks postoperatively is higher, than of surgical treatment with a laser
irradiation power 15 W. In a varicose disease of the lower extremities there were
observed the raising of the blood volume toughness, superficial relaxation and
superficial stress on background of reduction of the toughness--elasticity
module, superficial toughness and superficial elasticity. Crossectomy conduction
did not influence the integral dynamics of adsorption--rheological properties of
venous blood, but in 1 month after endovasal laser coagulation a normalization of
physicchemical parameters of blood was noted. Application of laser irradiation of
the 10 W power and less promotes inhibition of the relaxation properties of
venous blood; a prognostic meaning owes initial value of the blood volume
toughness.
PMID- 26419036
TI - [IMPACT OF PERINATAL TACTICS ON THE POSTOPERATIVE PERIOD COURSE IN SURGICAL
ELIMINATION OF AORTAL COARCTATION IN NEWBORN BABIES].
AB - The results of perinatal management and surgical treatment of 30 newborn babies,
owing antenatally diagnosed isolated aortal coarctation (AC) and 40 newborn
babies, in whom this diagnosis was not established antenatally, were analyzed.
Application of antenatal diagnosis and optimization of the patients' perinatal
management algorithm have permitted to reduce the treatment duration in the
intensive therapy division of cardiosurgical department. In newborn babies, to
whom the diagnosis of AC was established antenatally, a trustworthy reduced
duration of postoperative pulmonary artificial ventilation was revealed in
comparison with such in patients, in whom this diagnosis was not established
antenatally.
PMID- 26419037
TI - [BIOMECHANICAL SUBSTANTIATION OF ONE-AXIS DEFORMITY OF ADIPOSE-CUTANEOUS FLAPS OF
TEMPORAL AND ZYGOMATIC AREAS WHILE PERFORMANCE OF UPPER RHYTIDOPLASTY].
AB - The urgency of the problem of determining the biomechanical features adipose
cutaneous grafts due to a significant increase in the frequency of performing
cosmetic surgery and the lack of a unified concept for such interventions. In 32
women aged 35 to 65 years, which will eliminate the excess soft tissues in the
implementation ritidectomy and other surgical interventions, isolated patches of
adipose-cutaneous flaps to determine the mechanisms of its plastic deformation.
Based on the analysis of biomechanical research targeted the optimal stretching
the boundaries of adipose-cutaneous flaps zygomatic--to (0.45 +/- 0.021) cm and
temporal--by (0.0165 +/- 0.002) cm refer to areas that allowed to perform surgery
with preservation of natural topographoanatomic relations persons in the
performance of the upper ritidectomy.
PMID- 26419038
TI - [MODERN METHODS OF PROGNOSTICATION OF THE RECURRENCES OCCURRENCE AFTER SURGICAL
TREATMENT OF THE MAMMARY GLAND BENIGN TUMORS].
AB - Modern schemes of the recurrences predicting after surgical treatment of benign
tumors of mammary gland (BTMG) were estimated. In accordance to data of
retrospective investigation obtained, the recurrences occurrence rate through a
five-year period of observation have constituted 2.3%. While doing prospective
observation, the recurrences after treatment have occurred in 12 (24.0%)
patients, suffering phylloid histologic form of tumor. The BTMG recurrences were
noted predominantly in women--carriers of mutant alleles with polymorphism
rs8190924 of gene GSR and AA rs3763511--of gene DKK4. Nethertheless, there are no
data, which confirm the recurrence occurrence risk to be considered genetically
determinated, the possibilities ratio for this kind of polymorphism have
costituted 12.0 (trustworthy interval 95% 0.8 - 14.9).
PMID- 26419039
TI - [THE ROLE OF TUMORAL STROMA IN PREDICTING OF THE SEVERITY COURSE IN PATIENTS,
SUFFERING MAMMARY GLAND CANCER WITH P53 HYPEREXPRESSION].
AB - There was revealed, that the survival indices in mammary gland cancer (MGC)
patients in similar stage of the disease, in the same tumor histology, and in a
mutant gene p53 hyperexpression, to whom identical complex treatment was
conducted, are rhythmic, what witnesses a necessity to search for additional
predicting factors. Predicting role of tumoral stroma in patients, suffering MGC
with p53 hyperexpression, was studied.
PMID- 26419040
TI - [THE METHOD OF COLPOPOIESIS IN AN URINARY BLADDER EXTROPHY].
AB - Complex of extrophy--epispadias--a rare inborn malformation of genitourinary
system, abdominal wall muscles and pelvic bones. The observation was adduced,
concerning an urinary bladder extrophy in a girl in combination with vaginal
agenesia after noneffective primarily--postponed closure of urinary bladder,
osteotomy (in the age of 4 yrs old), with consequent ureterosygmostomy. In the
patient there was conducted a reconstructive operation for vagina creation, using
nonfunctioning bladder, right-sided nephrectomy for severe ureterohydronephrosis,
reconstruction of anterior abdominal wall and external genitalia.
PMID- 26419041
TI - [COMPARISON OF THE OCCURRENCE RATE OF NAUSEA AND VOMITING AFTER TRANSCUTANEOUS
NEPHROLITHOTRIPSY: SEVOFLURANE OR PROPOFOL].
AB - Impact of various kinds of general anesthesia while performing transcutaneous
endoscopic interventions on kidneys on postoperative occurrence and rate of
nausea and vomiting were studied. Propofol and sevofluran were used for support
of general anesthesia conduction. There was established, that if optimal depth of
anesthesia is maintained (bispectral index 40 - 60 units), the rate of nausea and
vomiting occurrence do not depend on the kind of anesthesia applied--total
intravenous or the inhalation one.
PMID- 26419042
TI - [IMPACT OF THE UPPER URINARY WAYS DRAINAGE METHOD ON RESTORATION OF RENAL
FUNCTION IN PATIENTS, SUFFERING ACUTE OBSTRUCTIVE PYELONEPHRITIS].
AB - Renal function was studied, using radionuclide renography, in 142 patients,
suffering acute obstructive pyelonephritis, in 73 of whom transcutaneous
nephrostomy was applied and in 69--the ureter's stenting, for the urine passage
restoration. The investigation was peformed in 1 month and 1 year after
miniinvasive treatment. After comparison of the investigation results there was
established, that after transcutaneous nephrostomy, using miniinvasive
technologies, the affected kidney's functional inhibition was trustworthy less,
than after stenting. Because of better preservation of renal function, the
transcutaneous nephrostomy conduction in patients, suffering an acute obstructive
pyelonephritis, constitutes a less invasive method, than the ureter's stenting.
PMID- 26419043
TI - [ESTIMATION OF CLINICAL EFFICACY OF MODIFIED LASER VAPORISATION FOR BENIGN
PROSTATIC HYPERPLASIA].
AB - The clinical efficiency of the method modified technique of laser vaporization of
the prostate in patients with benign prostatic hyperplasia were analysed.
Clinical efficacy method modified technique of laser vaporization according to
IPSS, Q(max) and V(res) was higher than the laser vaporization and did not differ
from TURP in patients with prostate volume of 80 ml. In patients with prostate
volume over 80 ml modified technique of laser vaporization clinical efficacy was
higher than prostatectomia.
PMID- 26419044
TI - [METABOLIC INTOXICATION IN THERMIC TRAUMA].
AB - In 76 injured persons with deep and superficial burns, having area from 3 to 65%
of the total body surface and ageing 5-16 yrs old, there was investigated the
impact of early surgical treatment on the metabolic intoxication severity in
accordance to content of the oxidatively modified proteins carbonyl groups in the
blood serum, and of a ceruloplasmin, what was considered as integral express
index of the organism antioxidant system state. Changes of these indices in
ambustial disease of middle severity have witnessed a sufficiently compensated
reaction of organism: of severe and extremely severe one--there were noted a
deficiency of the organism antioxidant defense; and in stages of toxemia and
septicotoxemia--attrition of the organism oxidant reserves and danger of the
septic complications occurrence. Conduction of early surgical intervention have
guaranteed maintenance of a ceruloplasmin content in stages of toxemia and
septicotoxemia on the level of healthy persons, relief of the ambustial disease
course, absence of critical metabolic intoxication and carbonyl stress, reduction
of the septic complications rate in 1.5 times.
PMID- 26419045
TI - [An Analysis of the Controversy on the Psychoprophylaxis Method in the Japanese
Medical Journal "Obstetrics and Gynecology," 1954-1957].
AB - The methods of painless childbirth are generally divided into two kinds: "with
drugs" and "without drugs." In Japan, the full-scale initiation of these two
types of painless childbirth methods in clinical practice started in the early
1950s. The practice of the psychoprophylaxis method (PPM)--one of the painless
childbirth methods "without drugs"--started in 1953. Japanese obstetricians had
discussed the practicability of PPM for painless childbirth and had doubted the
scientific nature and originality of PPM as a viable method. Therefore, they
published a series of articles in the Japanese medical journal "Obstetrics and
Gynecology" from 1954 to 1957. Two representative obstetricians developed this
controversy. Naotaro KUJI, the director of the Central Maternity Hospital of the
Japanese Red Cross Society and the chief practitioner of PPM, emphasized that PPM
was a more practical method, considering the Japanese medical legal situation
where midwives were prohibited to use drugs. On the other hand, Kakuichi ANDO,
the chief professor of the Department of Obstetrics and Gynecology of Keio
University and the team leader of the practitioners of painless childbirth "with
drugs," doubted the practicability of PPM. In the course of these discussions,
both groups of obstetricians gradually came to a consensus to use the concept of
"pain relief" in labor, instead of "painless" childbirth. They also agreed to
adopt methods "with drugs" and "without drugs," including PPM, according to the
presented case.
PMID- 26419046
TI - [Details and Background on the Origins of Modern Female Doctors in the Meiji Era:
Research on the Minutes of the Central Board of Health (see text) in Hosokawa
Junjiro's (see text) Monographs Goen-Sosho (see text) and Materials of the Bureau
of Hygiene (see text)].
AB - This research is based on materials of the Bureau of Hygiene (see text) and the
minutes of the Central Board of Health (see text) contained in Hosokawa Junjiro's
(see text) monograph Goen Sosho (see text). It showed that the movement toward
allowing the qualification of modern female doctors in Japan was going on in
various parts of Japan from 1881 or earlier. This history shows the presence of
many female doctors in the Edo Period. At an extraordinary meeting of the Central
Board of Health, an advisory body of the Bureau of Hygiene, the qualification of
female doctors was approved of in 1881. This was based on an article in the
yororyo law (see text) about female doctors contained in the ancient laws of
Japan. As a result, the Department of the Interior allowed female doctors in
June, 1884. At this time, five females took the national examination for medical
practitioners. The following year, Ogino Ginko (see text) became the first modern
female doctor in Japan. Owing to the yororyou law about female doctors, and the
efforts of many other females who wanted to become doctors, the first modern
female doctors in Japan came into being.
PMID- 26419047
TI - [Premature Death Problems of the Meiji Emperor's Infants, According to the Two
Submissions of 1883 and 1888].
AB - The Meiji Emperor had fifteen children; five princes and ten princesses, but ten
of them died of a meningitis-like disease in their infancy. People were concerned
about the circumstances in which the lineage of the emperor's family was in a
critical situation. They investigated the conditions regarding the children's
upbringing and reported on the matter to higher officials in 1883 and 1888. But
the author concludes that conditions did not change for the better because of
those efforts.
PMID- 26419048
TI - Looking forward. The University of New Mexico Hospital's memorial service to
their patients who have died.
PMID- 26419049
TI - Defining your own success: An introduction.
PMID- 26419050
TI - Talking the talk: The keys to effective workplace communication.
PMID- 26419051
TI - The RAS-ACS: Recruiting medical students and training future leaders.
PMID- 26419052
TI - Teaching in the OR: New lessons for training surgical residents.
PMID- 26419053
TI - Feedback fundamentals in surgical education: Tips for success.
PMID- 26419054
TI - Political advocacy in surgery: The case for individual engagement.
PMID- 26419055
TI - Surgeons and social media: Threat to professionalism or an essential part of
contemporary surgical practice?
PMID- 26419056
TI - No quality without access: ACS and NIH collaborate to ensure access to optimal
care.
PMID- 26419057
TI - The importance of detailed documentation in ICD-10.
PMID- 26419058
TI - Resources for optimal patient care: EBDS and patient education programs.
PMID- 26419059
TI - PACES trial: Evaluating the effectiveness of eflornithine and sulindac in
preventing colon adenomas.
PMID- 26419060
TI - Addressing surgeon fatigue and sleep deprivation.
PMID- 26419061
TI - Dr. Henri Ford performs first separation of conjoined twins in Haiti.
PMID- 26419062
TI - NTDB data points: A hot mess: Clothing-related burn injuries.
PMID- 26419063
TI - [BIOINFORMATICS COMPARISON OF HUMAN AND PLANT PHOSPHATOMES].
AB - The study presents the results of bioinformatic comparison of protein
phosphatases from higher plants and human phosphatom (150 sequences). Based on
sequence and profile comparison with known catalytic domains, 204 plant
homologues from Physcomitrella patens and Arabidopsis thaliana where selected.
Clustering of joint group of plant and mammalian protein phosphatases revealed
fundamental differences in plant and human phosphatomes. At the same time, it was
shown significant differences in the set of protein phosphatases in P. patens, A.
thaliana, and such monocots as Orysa saliva and Zea mays.
PMID- 26419064
TI - HIGH FREQUENCY GENETIC TRANSFORMATION OF CICHORIUM INTYBUS L. USING nptII GENE AS
A SELECTIVE MARKER.
AB - Cichorium intybus L. is an important vegetable crop used as salad (leaf form) and
for the production of coffee substitutes (root form). At the same time these
plants can also be used in biotechnologies for synthesis of pharmaceutical
proteins. Here we report the possibility of high frequency Agrobacterium
rhizogenes- or A. tumefaciens-mediated transformation of C. intybus L. for
construction of transgenic "hairy" roots and plants. The used plasmids contained
target human interferonifn-alpha2b gene, Mycobacterium tuberculosis ESAT6:Ag85B
antigene esxA::fbpB(DeltaTMD) fused gene and human telomerase reverse
transcriptase h Tert gene. Using of nptII gene as a selective one was preferable
to the bar gene for chicory. In this case the frequency of transgenic plants or
"hairy" roots formation was significantly higher. Cultivation of explants on the
medium with Basta in concentration 1-2 mg/l have led to plants death or to
significant reduction of number of shoots formed. Frequency of "hairy" roots
formation varied from 5.9 to 42.3% after A. rhizogenes-mediated transformation.
Frequency of regeneration of transgenic plants varied from 10 to 86% after A.
tumefaciens-mediated transformation. Both A. rhizogenes- and A. tumefaciens
mediated transformation frequency depended on the type of explants, roots or
cotyledons, and vector used. Usage of A. tumefaciens carrying pCB064 plasmid
(target esxA:fbpB(DeltaTMD) fused gene and nptII selective gene) resulted in the
most effective regeneration of transgenic plants with regeneration frequency up
to 86%. In the case of chicory A. rhizogenes-mediated transformation the highest
regeneration frequency up to 42.3% was demonstrated using p CB161 vector with ifn
alpha2b target gene and nptII selective gene.
PMID- 26419065
TI - DOES THE PATTERN OF CLONAL EVOLUTION IN THE KARYOTYPE OF PATIENTS WITH ACUTE
MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROMES DEPEND ON THE TYPE OF THE PRIMARY
CHROMOSOMAL ABERRATIONS?
AB - The aim of our study was to define if the type of primary chromosomal aberrations
(CA) of the karyotype of patients with Acute myeloid leukemia (AML) and
Myelodysplastic syndromes (MDS) determines the way and the rate of karyotype
development. Conventional cytogenetic analysis was carried out on 248 AML and 105
MDS patients at diagnosis. Clonal evolution (CE) was found in 40% (51 of 128) of
AML patients and in 47.5% (19 of 40) of MDS patients having CA in their
karyotype. The first pattern we established was for the most frequent CA which
initiate CE in 28 patients with a complex karyotype. These CA were non-balansed
rearrangements in the following regions: 5q, 7q, 11q, 3q, monosomy 5, monosomy 7.
The second pattern of CE was regarding the most frequent aneuploidias (+8, +11,
+21, -Y, and the third pattern concerned balanced CA. We found significant
difference in the distribution of karyotypes in different stages of progression
between the first and the other two groups (p < 0.001). No statistical difference
was found between the patterns in the second and the third group CA (p > 0.5).
PMID- 26419066
TI - OPTIMISATION OF TOTAL RNA EXTRACTION FROM BOVINE OOCYTES AND EMBRYOS FOR GENE
EXPRESSION STUDIES AND EFFECTS OF CRYOPROTECTANTS ON TOTAL RNA EXTRACTION.
AB - Gene expression is required for understanding bovine oocytes meiotic maturation
as well as the potential of embryonic development. In the present study a
standardized reagent protocol for total RNA extraction was designed for bovine
oocytes and embryos, which is considered specific and less expensive. For such
purpose oocytes (n = 795) recovered from about 80 ovaries were divided in three
groups: Group 1 modified Trizol (MTP, n = 355); Group 2 Guanidinium thiocyanate
protocol (GNTC, n = 140) and Group 3 Commercial Kit protocol (CKP, n = 60).
Oocytes belonging to group 1 (n = 100) and 3 (n = 20) were subjected to
vitrification using two cryoprotectants 1,2 propandiol (PROH) or
Dimethylsulfoxide (DMSO). The 240 remaining oocytes were divided into 3 groups in
which 100 were used, in fresh, for in vitro fertilization, and 140 oocytes were
vitrified using PROH (n = 70) and DMSO (n = 70) as cryoprotectants, being then
fertilized in vitro after thawing. Embryos were used nine days after
fertilization. Gene amplification (SDHA, (GAPDH and DNMT1) was performed in
oocytes, and gene quantification (DNMT1) in in vitro produced embryos at the
stage of blastocyst (n = 10). Efficiency of the extraction was further compared.
The purity of all samples to different protocols ranged from 1.10 to 1.25 for
GNTC protocol; from 2.05 to 2.63 for the CKP and from 1.50 to 2.11 for the
developed MTP, being the last one nearest to the expected purity levels for RNA
samples (1.7 to 2.0). On average, for 30 fresh oocytes, from spectrophotometer
readings, total RNA concentration was 127.8 +/- 9.3 ng MUl(-1) for MTP, against
46.4 +/- 9.5 ng MUl(-1) from CKP and 476 +/- 12.9 ng MUl(-1) for GNTC protocol.
Using the MTP to evaluate RNA in 30 vitrified/thawed oocytes, resulted in a total
RNA concentration of 61.3 +/- 3.3 ng MUl(-1) and 40.0 MU 12.4 ng MU(-1),
respectively for DMSO and PROH. Regarding total RNA concentration and purity, in
blastocyst stage, more purity was observed in DMSO as compared to PROH (1.8 vs
1.2) (p < 0.05). Better results were also observed on the MTP for gene
amplification when compared with the other protocols. For gene quantification,
the proposed protocol quantified DNMT1 gene with PCR efficiency (0.933) after
normalization against GAPDH and SDHA. Amplification and quantification of genes
proved specificity and efficiency of the MTP over the other protocols.
PMID- 26419067
TI - ZNF527 GENE rs386809049 ANALYSIS IN POPULATION OF UKRAINE.
AB - It was shown that some mutations in a number of zinc finger protein (Znf) genes
cause intellectual disability (ID). In our study in two affected siblings with ID
exome analysis revealed the homozygous coding sequence (cds) indel rs386809049 in
the ZNF527 gene. The c.806_808 deletion CAT and insertion TGTGCA (rs386809049)
results in substitution of Pro269 and Tyr270 to Leu, Cys and Asn, located in the
interdomain region of Zinc finger protein 527. The analyses of site orthologs
revealed that Pro269 and Tyr270 amino acid positions are conserved across
mammalian species, indicating that there may be an evolutionarily conserved
function. To evaluate the ZNF527 gene involvement in intellectual disability
pathogenesis analysis of rs386809049 polymorphism in 300 individuals from general
population of Ukraine was performed. The following genotypes distribution was
detected: CAT/CAT (67.7%), CAT/TGTGCA (31%) and TGTGCA/TGTGCA (1.3%). As far as
we know this is the flirt published data on rs386809049 distribution in the
populations. The ZNFS27 TGTGCA (polymorphic) allele frequency was 16.8% and
CAT(wild type)--83.2% in the general population of Ukraine. Such a high
polymorphic allele frequency allows us to suggest that analyzed rs386809049
polymorphism in ZNF527 gene cannot be the major cause of intellectual disability.
PMID- 26419068
TI - [GENE POOL SIMILARITIES AND DIFFERENCES BETWEEN UKRAINIANS AND RUSSIANS OF
SLOBOZHANSHINA ON Y-CHROMOSOME DATA].
AB - The results of the study of Y-chromosomal polymorphisms of Russian and Ukrainian
population are presented for Slobozhanshina--contemporary border region, former
"Wild Field" boundary, which was inhabited in XVII-XVIII centuries by both the
Russians from the north and Ukrainians from the west. In general, Ukrainian and
Russian populations of Slobozhanshchina genetically are very close, their set and
frequency range of Y-chromosome haplogroups are typical for the Eastern Europe.
But a detailed analysis of highly informative Y-chromosome markers showed that
after 3,5 centuries of coexistence on the same historical territory, the both
nations retain the ethnic specificity of their gene pools: Ukrainian populations
are similar to the rest of Ukraine, and Russian populations are similar to the
south of the European part of Russia. The genetic differences may be due to the
spatial characteristics of marriage migration and the predominant ethnic
environment.
PMID- 26419069
TI - [PREIMPLANTATION DEVELOPMENT OF HUMAN EMBRYOS WITH NUMERICAL CHROMOSOME
ABNORMALITIES IN VITRO].
AB - The study was focused on morphokynetic characteristics of in vitro cultured human
embryos that were considered to be aneuploid or euploid according to the
preimplantation genetic screening results. Among all the embryos examined only
34.2% were chromosomally balanced, while others possessed isolated or combined
chromosome abnormalities. Although morphological features of cleaving pathologic
and euploid embryos did not differ significantly, on the fifth day of culture
chromosomally balanced specimen formed "expanded" blastocyst twice as frequently
as abnormal ones. Moreover, development of 38.4% of aneuploid embryos was
compromised before the initiation of cavitation. Thus, prolonged embryo culture
advances selection of samples with the highest implantation potential for the
transfer on the basis of the morphokynetic characteristics and helps to avoid
additional genetic testing.
PMID- 26419071
TI - [INITIAL EXPERIENCE OF TRANSVAGINAL EXTRACTION OF THE KIDNEY FOLLOWING
LAPAROSCOPIC NEPHRECTOMY IN OUR DEPARTMENT].
AB - PURPOSE: We report the detailed technique and results of transvaginal extraction
of the kidney following laparoscopic nephrectomy. PATIENTS AND METHODS: From
August 2013 onward, we planned to perform transvaginal extraction of the kidney
following laparoscopic nephrectomy in a total of 6 female patients. Of the 6
patients, 5 underwent the procedure. After completion of the primary laparoscopic
nephrectomy and entrapping the removed kidney, the patients were placed in the
supine lithotomy position. A transverse posterior colpotomy was created
transvaginally at the apex of the posterior fornix. An opening was made in the
peritoneum bluntly with the fingers under laparoscopic view. After the drawstring
of the entrapped specimen was delivered into the vagina, the specimen was
extracted intact via the vagina. When the vaginal wall was too tight for a large
specimen, the incision was extended on the affected side. After removal of the
specimen, the peritoneum was sutured laparoscopically, and the posterior
colpotomy incision was repaired transvaginally. RESULTS: Transvaginal extraction
was successful in 5 patients. The mean operative time for the vaginal extraction
procedure was 59 minutes. Blood loss was minimal. The mean specimen weight was
447 g (range 271 to 655 g). No intraoperative complications occurred.
Postoperatively, one case needed intermittent catheterization for a few days
because of temporal dysfunction of the bladder. CONCLUSIONS: Transvaginal
extraction is an efficacious and minimally morbid technique for removing the
intact kidney after laparoscopic nephrectomy.
PMID- 26419072
TI - [CLINICOPATHOLOGICAL STUDY OF PROSTATE BIOPSY IN PATIENTS RECEIVING DUTASTERIDE
FOR BENIGN PROSTATIC HYPERPLASIA].
AB - OBJECTIVE: Dutasteride is a 5-alpha reductase inhibitor used to treat benign
prostatic hyperplasia. Dutasteride lowers prostate-specific antigen (PSA) levels,
which may lead to delays in the diagnosis and treatment of prostate cancer (PCa).
This study investigated patients who underwent prostate biopsy (PBx) while
receiving dutasteride to investigate whether this agent affects the diagnosis and
treatment of PCa. PATIENTS AND METHODS: PBx was performed on six patients
receiving dutasteride for > 3 months at our medical institutions between January
2010 and June 2013. No patients underwent PBx before dutasteride administration.
We performed PBx both for patients with high initial PSA levels and for those
with elevated PSA levels with or without initial PSA decline after dutasteride
administration. We also investigated clinicopathological findings. RESULTS: Mean
age at the start of administration was 69.5 +/- 5.9 years (range, 59-77 years),
mean duration of administration was 14.1 +/- 7.4 months (range, 4.0-23.5 months),
mean prostate volume at the start of administration was 70.4 +/- 30.7 ml (range,
18.8-104.6 ml), and mean PSA level at the start of administration was 7.7 +/- 3.3
ng/ml (range, 4.9-14.2 ng/ml). PSA density was 0.098 +/- 0.045 ng/ml/cm3 (range,
0.042-0.181 ng/ml/cm3), and PSA level at PBx was 5.4 +/- 2.7 ng/ml (range, 2.5
10.7 ng/ml). We detected three PCa patients, and clinical stage in each case was
cT1cN0M0. Radical retropubic prostatectomy was performed in two cases, and
androgen-deprivation therapy was performed in one case. CONCLUSION: All PCa were
detected in the early clinical stage. No delays in detection or treatment of PCa
were seen in any cases. Careful observation of PSA levels is simple and useful
for detecting PCa in patients under dutasteride administration.
PMID- 26419073
TI - [TREATMENT OUTCOME OF OBSTRUCTIVE PYELONEPHRITIS DUE TO URETERAL CALCULI WITH
DISSEMINATED INTRAVASCULAR COAGULOPATHY].
AB - OBJECTIVES: Because obstructive pyelonephritis secondary to ureteral stones can
easily cause sepsis and concomitant disseminated intravascular coagulation (DIC),
it is a potentially lethal disease. However, the optimal treatment for such
severe patients has yet to be established. In this study, we aimed at clarifying
the effectiveness of emergent drainage and DIC treatments for patients with
septic DIC due to obstructive pyelonephritis. In additon, we also evaluated the
impact of recombinant human thrombomodullin (rTM) for severe patients with DIC.
MATERIALS AND METHODS: From September 2006 to May 2013, 31 patients with
obstructive pyelonephritis secondary to ureteral stones who met the acute DIC
criteria from the Japanese Association of Acute Medicine were treated at our
institution. All patients received emergent drainage of urinary tract and anti
DIC treatment, as well as administration of antibiotics and adequate volume
infusion. To evaluate the impact of rTM, patients received rTM were compared with
those managed by other DIC therapeutic agents. RESULTS: The mean patients' age
was 73 years old, and 27 patients (87.1%) were in a state of septic shock. All
patients, except for one patient (3.2%) who died 6 days after drainage, could
recover from sepsis and comcomitant DIC. Interestingly, thrombocyte count,
creatinine, and SOFA Score in rTM group were recovered faster than those in no
rTM group (p = 0.017, 0.0038, and 0.0006, respectively). CONCLUSIONS: These
results indicate that most patients with DIC caused by obstractive pyelonephritis
can be successfully managed by emergency drainage and anti-DIC treatment. In
addition, rTM may be effective for the treatment of such severe patients by
improving organ failure associated with disordered coagulation.
PMID- 26419074
TI - [THE IMPACT OF LOWER URINARY TRACT SYMPTOMS ON GENERIC HEALTH-RELATED QUALITY OF
LIFE IN MALE PATIENTS WITHOUT CO-MORBIDITY].
AB - PURPOSE: We investigated the impact of lower urinary tract symptoms (LUTS) on
generic health-related quality of life (HRQOL) in male patients without co
morbidity. PATIENTS AND METHOD: From 2003 to 2011, a total 567 men who presented
out urological department completed the questionnaires including International
Prostate Symptom Score (IPSS), incontinence-frequency score (IFS) from the UCLA
prostate cancer index, MOS 36-Item Short-Form Health Survey (SF-36). Among 230
patients with no coexisting morbidity, the relations between each LUTS score of
IPSS indices and IFS and 8 domain scores of SF-36 were analyzed by Pearson's
product-moment correlation and stepwise multiple regression analysis. RESULT:
Univariate analysis showed that the IFS had a significant correlation with all of
8 domain scores of SF-36, and also the IPSS item scores of urgency, nocturia and
straining correlated significantly with multiple domain scores of SF-36. In
multiple regression analysis, the proportionate contributions of LUTS to each SF
36 domain scores were low (R2 was 10% or less). Incontinence was considered as
the most influential factor that had a negative impact on HRQOL in 7 SF-36
domains of physical functioning, role-physical, bodily pain, general health
perception, vitality, social functioning and mental health. Additionally,
nocturia, straining and urgency were significantly associated with deficit of
HRQOL in 4 SF-36 domains (role-physical, general health perception, role
emotional, mental health), 2 domains (bodily pain, social functioning) and 1
domain (role-emotional) of SF-36, respectively. CONCLUSION; Among LUTS,
incontinence, nocturia and straining were the most important symptoms in
association with the negative impact on generic HRQOL measured by SF-36.
PMID- 26419075
TI - [PRIMARY MEDIASTINAL GERM CELL TUMOR ARISING IN A PATIENT WITH NEUROFIBROMATOSIS
TYPE 1].
AB - Neurofibromatosis type 1 (NF1) is a distinct genetic disorder due to the NF1 gene
mutation which induces the aberrant activation of the RAS-signaling. Because RAS
related proteins function as oncogenic factors, NF1 patients frequently develop
malignant tumors, especially of neural crest origin, such as peripheral nerve
sheath. In addition, malignant tumors of the pancreas, colorectum, and lung have
been reported to frequently arise in NF1 patients. However, the association
between germ cell tumor and NF1 has not been clarified yet. A 29-year-old male
with dyspnea was referred to our hospital because of the large mass in the
anterior mediastinum and cervical lymph node swelling. The diagnosis was
extragonadal germ cell tumor with cervical lymph node metastasis, and complete
remission was obtained by multidisciplinary treatment consisted of combination
chemotherapy and surgical resection. To our acknowledgement, this is the first
case of extragonadal germ cell tumor in NF1 patients. We discuss the relevance
between activation of the RAS-signaling and the development of germ cell tumor.
PMID- 26419076
TI - [A CASE OF SOLITARY ADRENAL TUMOR METASTASIZED FROM RECTAL CANCER].
AB - Solitary adrenal metastasis of rectal cancer is comparatively rare condition and
it is difficult to be diagnosed because it doesn't have any characteristic
symptoms. We report a case of this type of adrenal tumor that could be figured
out by tumor markers and the analysis of CT scan image. A 67-year-old man visited
our department with the right adrenal tumor. He has a past medical history of
rectal cancer and a low anterior resection was performed in 2011. After the
surgery, he received adjuvant chemotherapy for 6 months. There has been no
finding of recurrence or metastasis after chemotherapy. However, his follow-up
abdominal CT in 2013 showed the right adrenal tumor which was 23 mm in diameter.
Serum CEA level has also increased to 4.1 ng/ml, but there was no abnormal
finding with hormonal study. The tumor size and CEA level gradually increased up
to 46 mm in size and 10.4 ng/ml during 6 months. Enhanced CT also showed 39% at
rate of absolute percentage wash out, which was not the finding of typical
functional adrenal tumor. Based on these findings, we diagnosed that the origin
of this adrenal tumor should be solitary metastasis of the rectal cancer. For the
treatment of surgical procedure, we performed laparoscopic right adrenalectomy.
The pathological finding showed adenocarcinoma, the origin of which was the
previous rectal cancer. Six months have passed since the surgery, but CEA level
still has remained normal range and neither finding of recurrence nor metastasis
has been found.
PMID- 26419077
TI - [A CASE OF HEPATIC METASTASECTOMY FOR RENAL PELVIS CARCINOMA].
AB - A 68-year-old woman presented with asymptomatic gross hematuria. Computed
tomography (CT) scan revealed noninvasive tumor in the right ureteropelvic
junction. After diagnosis with right pelvis carcinoma by ureteroscopy, she
underwent laparoscopic nephroureterectomy in Aug. 2008. Six months later, hepatic
metastasis was detected. Three courses of combination chemotherapy consisting of
gemcitabine and cisplatin (GC) were conducted, and then partial response (PR) was
achieved. In Aug. 2009, radical metastasectomy for liver metastasis was
performed. More than four years and five months after hepatectomy, the patient
has achieved a high quality of life.
PMID- 26419078
TI - [A CASE OF GRANULOCYTIC SARCOMA IN THE BILATERAL URETER].
AB - A 61-year-old female presented with the complaints of fever and left back pain.
She had previously undergone bone marrow transplantation for acute myeloid
leukemia and achieved remission. Abdominal computed tomography (CT) revealed left
hydronephrosis and suspected tumor lesions in the right upper ureter and left
lower ureter. Ureteroscopy was performed for a diagnosis. A yellowish tumor was
detected in the left lower ureter, and tissue biopsy was performed. Two weeks
after the examination, abdominal CT revealed ascites and retroperitoneal
dissemination. The results of the ascites cytology showed infiltration by
leukemia cells, and the patient was diagnosed as having recurrent leukemia. A
week later, she died. The ureteral tumor was diagnosed as a granulocytic sarcoma.
Granulocytic sarcoma, a condition characterized by mass formation outside the
bone marrow by granulocytic cells, is classified as a myeloid sarcoma, occurring
in an estimated 2-8% of patients with myeloid leukemia. The possibility of
granulocytic sarcoma should be considered when treating patients with a history
of leukemia.
PMID- 26419079
TI - [THREE CASE REPORTS OF METACHRONOUS BILATERAL TESTICULAR TUMOR: INVESTIGATION OF
SEXUAL FUNCTION AND FERTILITY].
AB - The sexual dysfunction and infertility after treatment of bilateral germ cell
tumors (GCT) becomes the serious problem. Therefore andrological aspects as well
as cancer curability should be considered in planning of bilateral GCT treatment.
Here we report 3 cases of metachronous bilateral GCT treated with different
regimens, and discuss from the viewpoint of preservation of sexual function. Case
presentations: (1) A 38-year-old man underwent right-sided orchitectomy for a
right testicular tumor at the age of 26 years. Pathological diagnosis was
seminoma and clinical stage was T1N0M0S2. 12 years later, contralateral
testicular tumor developed. Left-sided orchitectomy was performed. Pathological
diagnosis was seminoma and clinical stage was T1N0M0S2. He has been followed up
for 4 years after the second operation without any evidence of tumor recurrence.
Endocrinological examination show low testosterone level, and high LH and FSH
levels. Erection and ejaculation are impossible but he does not request androgen
replacement therapy. (2) A 21-year-old man underwent right-sided orchitectomy for
a right testicular seminoma at the age of 20 years (T1 N0M0S0). 1 year later,
contralateral seminoma (T1N0M0S0) developed and left-sided organ-preserving
operation was performed. Histologic specimens showed seminoma and intratubular
malignant germ cells (ITMGC) in surrounding seminiferous tubules. 2 cycles of BEP
was added after the operation. He has been followed up for 5 years without any
evidence of tumor recurrence. Endocrinological examination shows normal levels of
testosterone and LH, but FSH is slightly high. Erection and ejaculation are
possible. (3) A 36-year-old man underwent right-sided orchitectomy for a right
testicular embryonal carcinoma at the age of 30 years. Clinical T1N0M0S1 was
confirmed. 6 years later, he noticed the induration at his left testis. The
result of fine needle aspiration cytology was embryonal carcinoma. At first,
organ-preserving operation after chemotherapy was planned. However, he refused
the operation considering the possibility of erectile dysfunction and
infertility. As a result, he received only chemotherapy (3 cycles of BEP), and
has been free of the disease for 11 years after chemotherapy. The level of
testosterone, LH, and FSH are all normal. Erection and ejaculation are possible.
PMID- 26419080
TI - [A CASE OF UROTHELIAL CARCINOMA OF THE URINARY BLADDER WITH SQUAMOUS
DIFFERENTIATION RESPONDING TO PACLITAXEL AND CARBOPLATIN NEOADJUVANT
CHEMOTHERAPY].
AB - A 42-year-old man was referred to our hospital for macrohematuria. Computer
tomography and magnetic resonance imaging revealed right hydronephrosis and a
retroperitoneal mass, located next to right side of the bladder. Cystoscopy
showed a protruded lesion covered with normal mucosa at the right lateral wall.
The patient underwent transurethral resection of the bladder tumor and biopsies
of the bladder wall. Histological examination showed squamous cell carcinoma.
Neoadjuvant chemotherapy using paclitaxel and carboplatin (TC) was performed. A
total cystectomy, right nephroureterectomy and construction of the ileal conduit
were performed after one course of systemic chemotherapy. Histological
examination showed urothelial carcinoma with squamous cell differentiation.
Unexpectedly, a small amount of CIS was detected only in the vicinity of the TUR
scar. The patient received 2 cycles of TC chemotherapy as adjuvant chemotherapy.
Unfortunately, 11 months later, local recurrence and liver metastasis were
detected. He died 17 months after the surgery.
PMID- 26419081
TI - [LEIOMYOSARCOMA ARISING FROM OVARIAN VEIN WITH RIGHT HYDRONEPHROSIS: A CASE
REPORT].
AB - The patient was a 37-year-old woman who had suffered from repeated
pyelonephritis. Computed tomography (CT) of the abdomen revealed a 1.9 cm
retroperitoneal mass with compression of the right ureter and hydronephrosis. The
patient visited our medical center and admitted. The patient underwent a simple
total excision of the mass and end-to-end ureteral anastomosis. The tumor
involved right ovarian vein and right ureter. Histopathological diagnosis was
leiomyosarcoma of the ovarian vein. At 12 months after operation, local
recurrence of surroundings tissue of the right ureter and gallbladder, and
inferior vena cava invasion is found. Thus, the patient underwent a right
nephroureterectomy with partly resection of the inferior vena cava and en block
excision of the gallbladder. While CT revealed no recurrence three months after
the operation, adjuvant postoperative combination chemotherapy with gemcitabine
and docetaxel was administered. Nine cases of this leiomyosarcoma arising from
ovarian vein have been reported in the literature. Leiomyosarcoma arising from
ovarian vein with hydronephrosis is a second example.
PMID- 26419082
TI - [How relevant is the risk of losing evidence due to delayed blood sampling?
Conclusions from the evaluation of blood analysis results].
AB - If the order of a judge to take a blood sample can only be obtained with a marked
delay after the incident, evidence proving that a suspect had been driving under
the influence of alcohol or drugs of abuse may be lost. The evaluation of blood
analysis results from the Institute of Legal Medicine in Frankfurt/Main from the
years 2012-2014 shows that in 1.6 to 11.6% of positive cases, the drug
concentrations were near the legal limits (20.2% of alcohol-positive and 7.5% of
illicit drugs-positive samples). A loss of evidence can thus be expected in a
large number of cases when the time between the police check of a driver and the
collection of a blood sample increases. Blood concentrations of alcohol and drugs
of abuse, especially tetrahydrocannabinol, cocaine, methamphetamine, and
morphine, may already have dropped significantly after a delay of only half an
hour. These delays are typically due to the time elapsing until the order to take
a blood sample has been obtained from a judge and a medical doctor becomes
available and arrives at the police station to draw a blood sample. The
recommendation of medicolegal experts is to keep the time between police check of
a suspect and blood sampling as short as possible. In routine cases, a realistic
maximum of one hour should not be exceeded.
PMID- 26419083
TI - [Projection of prisoner numbers].
AB - The past and future development of occupancy rates in prisons is of crucial
importance for the judicial administration of every country. Basic factors for
planning the required penal facilities are seasonal fluctuations, minimum,
maximum and average occupancy as well as the present situation and potential
development of certain imprisonment categories. As the prisoner number of a
country is determined by a complex set of interdependent conditions, it has
turned out to be difficult to provide any theoretical explanations. The idea
accepted in criminology for a long time that prisoner numbers are interdependent
with criminal policy must be regarded as having failed. Statistical and time
series analyses may help, however, to identify the factors having influenced the
development of prisoner numbers in the past. The analyses presented here, first
describe such influencing factors from a criminological perspective and then deal
with their statistical identification and modelling. Using the development of
prisoner numbers in Hesse as an example, it has been found that modelling methods
in which the independent variables predict the dependent variable with a time lag
are particularly helpful. A potential complication is, however, that for
predicting the number of prisoners the different dynamics in German and foreign
prisoners require the development of further models.
PMID- 26419084
TI - [Drying time for human saliva].
AB - In a case of aggravated extortion under threat of force, the medicolegal expert
was asked to give an opinion on the drying time of human saliva. Fresh traces of
saliva were applied to composite stones similar to those at the scene of the
crime and their drying behavior was examined in a climate test chamber. Air
temperature and air humidity during the experiment corresponded to the values of
the measuring station located nearest to the crime scene. After one hour and 40
minutes no salivary spots were discernible on the stones any more. Depending on
various influence factors, the traces could have originated both at the time of
the offence and within a time window of up to 3 hours before.
PMID- 26419085
TI - [Sudden death of a 16-year-old girl with WPW syndrome: a case report].
AB - The Wolff-Parkinson-White syndrome is a usually benign heart disease with
accessory pathways. Circling excitations arise between atria and ventricles which
can lead to cardiac arrhythmias. Cases of sudden cardiac death are rare (0.2 %).
Risk factors for sudden cardiac death in patients with WPW syndrome are old age,
several accessory pathways, male sex and previous syncopes. A 16-year-old girl
was found lying dead in her bed. The evening before, she didn't feel well and
complained about abdominal pain. The girl had known epilepsy and Wolff- Parkinson
White syndrome. The macroscopic and histological findings are presented and
discussed with reference to the pertinent literature.
PMID- 26419086
TI - [Archaeology and criminology--Strengths and weaknesses of interdisciplinary
cooperation].
AB - Interdisciplinary cooperation of archaeology and criminology is often focussed on
the scientific methods applied in both fields of knowledge. In combination with
the humanistic methods traditionally used in archaeology, the finding of facts
can be enormously increased and the subsequent hermeneutic deduction of human
behaviour in the past can take place on a more solid basis. Thus,
interdisciplinary cooperation offers direct and indirect advantages. But it can
also cause epistemological problems, if the weaknesses and limits of one method
are to be corrected by applying methods used in other disciplines. This may
result in the application of methods unsuitable for the problem to be
investigated so that, in a way, the methodological and epistemological weaknesses
of two disciplines potentiate each other. An example of this effect is the
quantification of qualia. These epistemological reflections are compared with the
interdisciplinary approach using the concrete case of the "Eulau Crime Scene".
PMID- 26419087
TI - [Fatal skiing accidents: a forensic analysis taking the example of Salzburg].
AB - The rising popularity of Alpine skiing in recent years has led to an increase of
skiing accidents, some with fatal outcome. In this paper, all fatal skiing
accidents from the autopsy material of the Institute of Forensic Medicine of the
Paris Lodron University Salzburg were evaluated and compared with statistical
data of the Alpine Police. In the wintertime of 2005/2006 until 2013/2014, 22
deadly skiing accidents were autopsied. The age of the male and female victims
ranged between 12 and 71 years. The main cause of death was craniocerebral and
chest trauma. A relevant blood alcohol concentration was detected in only one
case. Together with trauma-biomechanical and technical experts, forensic medicine
serves as a necessary clarification interface between the investigating
authorities and the judiciary. Determining the cause and manner of death as well
as reconstructing the accident is the main task of the forensic pathologist. The
present study shows that in the county of Salzburg, only a small percentage of
fatal skiing accidents is evaluated from a forensic and trauma-biomechanical
point of view. Thus the possibilities of an interdisciplinary accident analysis
are not always fully utilized.
PMID- 26419089
TI - [Fatal electric accident due to adverse error situation].
AB - Despite wearing high-impedance shoes, a young male died while trying to connect a
garden pump (230 V). The cause of death could easily be determined on the basis
of testimonies of eye-witnesses and an electric mark on the body. Histological
and electron microscopic examinations showed metallisation of the electric mark
(pure iron). Intensive investigative efforts were needed, however, to reproduce
the current path, which resulted from three different coactive failures. The
electrotechnical characteristics of the case and the resulting current path are
described.
PMID- 26419088
TI - [Human frontal inclination of the skull as a trait of sexual dimorphism-
terminology and quantification].
AB - The skull presents a variety of morphological traits suitable for sex
discrimination due to the degree of their development. The vertical frontal
inclination has been established. as another marker of sex discrimination, as a
steep forehead is considered as a female and a receding frontal inclination as a
male attribute. In the literature, there are many different ways to define the
morphognostic term "frontal inclination" and "forehead profile" respectively. As
part of the project "Digital Forensic Osteology" definitions of the frontal
inclination commonly found in the literature have been tested with regard to
their applicability to virtual skulls based on post-mortem CT data. The actual
angle measurements were carried out automatically using software developed by the
authors of this article. For the investigations, profile images of skulls
generated from volume-rendered CT data were used in which anthropometric
measuring points had been set manually. With the help of discriminant analysis it
was tested whether sex discrimination on virtual skulls based on defined
variables can be carried out with sufficient sensitivity. The measurement
accuracy of the defined variables on the volume-rendered images turned out to be
good. No significant sex differences regarding the tested variables were found.
Using all the four selected variables the sensitivity for female skulls was only
about 66%, whereas for male skulls it was not much higher than the rate of
coincidence (53%). The results of this pilot study suggest that apart from
extending the sample size the inclusion of additional variables based on strict
consideration of validity and reliability criteria should be critically tested.
PMID- 26419090
TI - [In vitro characterization of glucuronosyl- and sulfotransferases involved in the
conjugation of ethanol].
AB - Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are minor metabolites of ethanol;
for some years, both compounds have been used as direct biomarkers of alcohol
consumption in forensic and clinical settings as well as in traffic medicine.
Drinking experiments showed individual variations of the formation of EtG and
EtS. At present, our knowledge on enzymes involved in the conjugation of ethanol
is incomplete and partly inconsistent. The purpose of the present study was to
characterize those enzymes that are capable of catalyzing glucuronidation and
sulfation of ethanol including some potential inhibitors. Following optimization
of incubation conditions, the formation rates of EtG and EtS from ethanol via
recombinant glucuronosyltransferases (UGTs, hepatic) and sulfotransferases
(SULTs, hepatic, intestinal), the kinetics and the inhibitory potential of
polyphenols such as quercetin, kaempferol and resveratrol were determined.
Analysis was performed following either solid phase extraction due to severe ion
suppression of EtG or direct injection of the EtS-containing incubation mixture
by high-pressure liquid chromatography/tandem mass spectrometry. Deuterated
analogues were used as internal standards. All UGTs were capable of metabolizing
ethanol through glucuronidation; UGT1A9 and UGT2B7 exhibited the highest
formation rates. All SULTs showed ethanol-sulfating activity with SULT1A1 being
most active. Data for all enzymes could best be described by Michaelis-Menten
kinetics. All polyphenols inhibited the conjugation of ethanol except UGT2B 15.
Inhibition was reversible and competitive for most enzymes; mechanism-based
inhibition was evident for UGT2B7 and SULT2A1 with regard to quercetin and for
SULT1E1 with regard to kaempferol. These results suggest an influence on the
formation rates of EtG and EtS by common food ingredients beside known
polymorphisms of UGT and SULT family members. Further studies should be conducted
to achieve a better understanding of the extent and significance of this
influence.
PMID- 26419091
TI - [Alleged suicide by insulin].
AB - A 26-year-old man, who was on probation, was found dead in his home by his
mother. Insulin vials and 2 insulin pens, which the man's stepfather (an insulin
dependent diabetic) had been missing for over a week, were found next to the
deceased. The circumstances suggested suicide by an injected insulin overdose. At
the time of the autopsy, the corpse showed already marked signs of autolysis.
Clinical chemical tests confirmed the injection of insulin, but indicated
hyperglycemia at the time of death. Toxicological analyses revealed that the man
had consumed amphetamine, cannabinoids, and tramadol in the recent past.
Histological examination finally revealed extensive bronchopneumonia as the cause
of death. The most plausible explanation for the results of the autopsy and the
additional examinations was an injection of insulin as a failed attempt of self
treatment. It is conceivable that the man had discovered by a rapid test that he
was a diabetic, but had decided not to go to a doctor to avoid disclosure of
parole violation due to continued drug abuse. He may have misinterpreted the
symptoms caused by his worsening bronchitis and the developing bronchopneumonia
as symptoms of a diabetic metabolic status and may have felt compelled to treat
himself with insulin.
PMID- 26419092
TI - [Death after the intake of amphetamine/ecstasy: two case reports].
AB - Synthetic amphetamines such as 3,4-methylenedioxy-N-methylamphetamine (MDMA,
Ecstasy) have become recreational drugs in German discotheques because of their
euphoric and mood-brightening effects. However, their consumption involves
considerable risks, which may even be lethal under certain circumstances. A 19
year-old man was taken to a university hospital for suspected intoxication with a
narcotic drug, where he died the next day. As cause of death "fulminant liver
failure" was diagnosed. In blood from the femoral vein, MDMA was found in a
concentration of 4.27 mg/l. Histological examination showed acute necrosis of the
liver and parenchymatous bleeding. The second case is that of a 39-year-old man
who collapsed at his workplace and died in hospital shortly afterwards. In his
rucksack, a small bag with 1.6 g of amphetamine was found. Analysis of blood from
the femoral vein showed an amphetamine concentration of 1.08 mg/l.
PMID- 26419093
TI - [Translational Research and Anesthesiology].
PMID- 26419094
TI - [Comparison of Seven Intubation Devices in Difficult Airway Model].
AB - BACKGROUND: The efficacy in tracheal intubation may differ between different
video-optical devices, in particular in patients with difficult airways. The
purpose of this study was to evaluate the efficacy of video-laryngoscopes and
fiberoptic bronchoscope (FOB) in tracheal intubation on a mannequin with several
difficult airways, including limited mouth opening, cervical spine rigidity and
tongue edema. METHODS: Residents performed tracheal intubation on a mannequin
using Macintosh laryngoscope (Mac), rigid indirect-optical intubation devices and
FOB. The laryngeal view, the success rate of tracheal intubation, and the time to
intubate trachea were recorded. RESULTS: With limited mouth opening and cervical
spine rigidity, video-optical intubation devices showed a significantly higher
success rate of tracheal intubation than the Mac or FOB. In contrast, with tongue
edema, the success rate of tracheal intubation was lower when Mac-type
videolaryngoscopes were used. CONCLUSIONS: Videolaryngoscopes can generally be
useful in patients with all difficult airways, but may be difficult in some
circumstances (such as tongue edema). The FOB provided good laryngeal view in all
cases, but the success rate of tracheal intubation was low and the time to
intubate trachea was long.
PMID- 26419095
TI - [Exposure to 1 % Sevoflurane for 6 Hours Enhances Proliferation of Human Colon
Cancer Cells].
AB - BACKGROUND: Sevoflurane is one of the commonly used volatile anesthetics in
cancer patients. The protective effect of sevoflurane preconditioning has raised
concerns about whether sevoflurane could act advantageously for survival even of
cancer cells. Therefore, we investigated the effects of sevoflurane on
proliferation in colon cancer cell lines. METHODS: HCT116 and HT29 cells were
plated in 96-well plates at a density of 1 x 10(4) cells/well and incubated
overnight. On the next day, cells were exposed to 1% or 2% sevoflurane for 6 hr.
After 24 hr recovery, we performed MTT assay. The absorbance of the formazan
product was measured at a wavelength of 570 nm using 650 nm as the reference. In
addition, to investigate the role of adenosine triphosphate-sensitive potassium
(K(ATP)) channels, we conducted the same experiment under co-administration of
K(ATP) inhibitor, glibenclamide. RESULTS: Only 1% sevoflurane significantly
enhanced cell proliferation compared to the control in HCT116 and HT29 cells.
Enhanced proliferation by sevoflurane was completely blocked by co-administration
with glibenclamide in HCT116 cells. CONCLUSIONS: We had shown that 1% sevoflurane
for 6 hr potentially enhances cell proliferation via K(ATP) channels in cancer
cells.
PMID- 26419096
TI - [The Effect of Preoperative Oral Rehydration on Hemodynamic Changes during
Induction of Anesthesia and Intraoperative Fluid Management].
AB - BACKGROUND: Preoperative oral rehydration solution (ORS) prevents dehydration
before surgery. Therefore taking enough ORS possibly reduces the hemodynamic
changes during induction of anesthesia, and reduces the amount of fluid needed
during anesthesia. METHODS: Forty patients undergoing elective surgery were
randomly assigned to two groups: drinking 1,500 ml ORS 6 to 2 hours before
anesthesia (ORS group) and nothing by mouth from 6 hours before anesthesia
(Control group). Anesthesia induction was performed using propofol and
remifentanil. To evaluate the hemodynamic changes, hemodynamic parameters
including heart rate, blood pressure, cardiac index (CI), and stroke volume
variation (SVV) were recorded before induction, after propofol administration,
and after remifentanil administration. Total urine volume and the amount of fluid
were also recorded at the end of the anesthesia. RESULTS: In ORS group, CI showed
a significantly higher value after propofol administration (P = 0.046). SVV was
significantly lower (P < 0.0001) and total amount of fluid during anesthesia was
significantly reduced (P < 0.0001) in ORS group. CONCLUSIONS: Preoperative oral
rehydration increases circulating blood volume, it keeps high CI during induction
of anesthesia, and reduces the amount of intraoperative fluid.
PMID- 26419098
TI - [Two Cases of Fetuses with Difficult Airway that Survived by the EXIT (Ex Utero
Intrapartum Treatment) Procedure].
AB - We successfully managed two fetuses complicated with suspected airway obstruction
after birth by the EXIT (ex utero intrapartum treatment) procedure, whose
placental circulation was maintained till their airway was secured during the
cesarean section. The first fetus was suspected to have airway obstruction due to
a large neck mass. At 36 weeks of gestation, the EXIT procedure was undertaken
performing the tracheal intubation successfully by laryngoscope. The second fetus
with micrognathia was expected to have airway obstruction after birth. The EXIT
procedure was undertaken at 35 weeks of gestation. The tracheal intubation by
laryngoscope or by stylet scope was impossible, and the airway was secured by
tracheostomy. The direct roles of anesthesiologists in the EXIT procedure are to
let the uterus relax enough, deal with bleeding, and manage the fetal airway. The
EXIT procedure is a specialized operation in which various specialists are
involved, and a variety of judgments are necessary within a short time.
Therefore, all concerned personnel should discuss previously to make a concensus
on the processes during the procedure. The organization may be also an important
role of the anesthesiologists in the EXIT procedure.
PMID- 26419097
TI - [Effects of Anesthetics on Perioperative Short-term Outcomes in Patients
Undergoing Thoracic Surgery with One-lung Ventilation].
AB - BACKGROUND: The present study was designed to evaluate the postoperative values
such as body temperature (BT), white blood cells (WBC), P/F ratio and C-reactive
protein (CRP) associated with propofol or sevoflurane in patients undergoing
thoracic surgery with one-lung ventilation. METHODS: We retrospectively reviewed
outcomes of patients undergoing video-associated thoracic surgery of the
esophagus (VATS-E) with propofol (group P, n = 71) or sevoflurane (group S, n =
34). Data were taken at 1 POD and 2 POD in ICU. In addition, data of WBC and CRP
were taken just before the operation and on 5 POD. Statistical analyses used t
value and two-way ANOVA with statistic significance as P < 0.05. RESULTS: There
was no significant difference between the two groups and we could not find the
correlation between anesthetics and each factor. CONCLUSIONS: Propofol and
sevoflurane had similar effect on BT, WBC, P/F ratio and CRP in patients
undergoing thoracic surgery with one-lung ventilation.
PMID- 26419099
TI - [Use and Safety of Preoperative Oral Rehydration Therapy Using a Jelly Type Oral
Rehydration Solution].
AB - BACKGROUND: Traditionally, perioperative nutritional management centered on fluid
therapy, but in recent years, with the spread of enhanced recovery after surgery
(ERAS) protocols, the utility of oral rehydration therapy (ORT) has been
reported. There are few reports, however, on the safety of using jelly type oral
rehydration solutions for ORT. We examined the effects of OS-1 jelly on gastric
fluid and investigated its safety. METHODS: A total of 147 patients (age range, 4
91 years), scheduled for elective surgery at our institution for whom ORT was
indicated, were enrolled in this study. If the surgery was scheduled for the
morning, patients were given two bottles of 200 g OS-1 jelly during the previous
evening meal. If surgery was scheduled for the afternoon, two additional 200 g
bottles were given to the patient with the morning meal on the day of surgery.
Patients were allowed to drink water until two hours before the surgery. Gastric
fluid was aspirated with a gastric tube after anesthesia induction, after which,
volume and pH were measured. RESULTS: In all cases, gastric content was aspirated
as a liquid, not a jelly. The volume and pH were 11.4 +/- 14.6 ml and 2.8 +/-
2.2, respectively. No major difference was seen in comparison with the data for
OS-1 liquid. No postoperative aspiration pneumonia or reflux of gastric contents
at the time of anesthesia induction was seen in any of the patients. CONCLUSIONS:
From the present findings, if the time of water intake is strictly controlled,
preoperative rehydration therapy using jelly-type oral rehydration solution is
thought to be safe and comparable to liquid solution regarding its effects on
gastric fluid.
PMID- 26419100
TI - [Ultrasound Analysis of the Anatomical Relationships between Vertebral Arteries
and Internal Jugular Veins in Adults].
AB - BACKGROUND: Accidental puncture of a vertebral artery can occur through the
internal jugular vein during central venous catheterization. METHODS: We
evaluated the anatomical relationships between vertebral arteries and internal
jugular veins in one hundred adult patients under general anesthesia using echo
image. RESULTS: The vertebral artery could be observed in all patients under the
level of cricoid cartilage. Vertebral arteries ran in an outward direction toward
the caudal side (3.9 mm lateral and 14.6 mm deep from the internal jugular vein :
median). Mean width of vertebral artery was 4.2 mm. Because the width of central
venous catheter guide wire is approx. 1 mm, accidental puncture of a vertebral
artery can occur through the internal jugular vein during central venous
catheterization. By the use of ultrasound analysis, the vertebral artery could be
observed completely. CONCLUSIONS: It is important to identify the location of
vertebral arteries under the level of cricoid cartilage and avoid the tap toward
the lateral side. We can avoid accidental puncture of vertebral artery by taking
care of these points.
PMID- 26419101
TI - [A Clinical Comparison of Continuous Sciatic Nerve Block and Epidural Anesthesia
for Postoperative Pain Control in Patients with Fracture of the Foot].
AB - BACKGROUND: Epidural analgesia provides good pain relief for patients with
fracture of the foot Ultrasound-guided peripheral nerve block offers safety and
efficacy without affecting the leg. METHODS: We compared the continuous sciatic
nerve block with the continuous epidural anesthesia regarding postoperative pain
after the open reduction and internal fixation (ORIF) of the ankle fracture or
calcaneal bone fracture. RESULTS: Fifteen patients were included in the epidural
group (group E), and 17 patients in the sciatic nerve block group (group S). The
postoperative pain scores were significantly lower in group S 3 hours and 12
hours after the procedure, and tended to be lower in other periods. Perioperative
periods were uneventful in both groups. CONCLUSIONS: Continuous sciatic nerve
block developed good postoperative analgesia in ORIF of ankle fracture or
calcaneal bone fracture compared with continuous epidural anesthesia.
PMID- 26419102
TI - [Difficult Airway Management of a Patient with the Ossification of Anterior
Longitudinal Ligament].
AB - We report a case of difficult airway management (DAM) with the ossification of
anterior longitudinal ligament (OALL). A 66-year-old man complained of pharyngeal
discomfort. He was diagnosed with OALL, and planned to have a surgery under
general anesthesia. We expected DAM due to the limitation of cervical mobility
and airway obstruction caused by OALL. We succeeded in awake intubation with
video laryngoscope and tracheal tube introducer.
PMID- 26419103
TI - [A Case of Postoperative Paraplegia Caused by Idiopathic Spinal Cord Infarction
following Hepatectomy under Both General and Epidural Anesthesia].
AB - A 73-year-old woman (height : 155 cm, weight : 55 kg) was scheduled to undergo a
laparotomic hepatectomy and radiofrequency ablation for hepatocellular carcinoma.
Her medical history did not include any relevant conditions such as
cardiovascular or neurological disorders. A thoracic epidural catheter was
introduced at T8-9 before the induction of anesthesia with intravenous propofol.
General anesthesia was maintained with the inhalation of oxygen, air, and
desflurane, and the continuous infusion of remifentanil. Several intraoperative
episodes of mild hypotension occurred, each of which was successfully treated
with intravenous ephedrine, but otherwise her anesthetic course was uneventful,
and she recovered from the anesthesia smoothly. Her postoperative pain was well
controlled with continuous epidural infusion of levobupivacaine and fentanyl, and
she could walk by herself on postoperative day (POD) 1. However, she suffered
weakness in her lower extremities on POD2 and subsequently fell into complete
paraplegia with sensory loss below the T4 level on POD3. A magnetic resonance
imaging scan taken on POD4 showed an idiopathic spinal cord infarction (SCI)
involving levels T1 through T4, although no epidural abnormalities, e.g.,
hematomas, were detected. Immediate treatment with methylprednisolone, ozagrel,
and edaravone failed to resolve her symptoms. We suggest that it is of great
importance to consider SCI as a differential diagnosis as soon as possible in
cases of unanticipated postoperative paraplegia.
PMID- 26419104
TI - [Anesthesia for Patients with Obstructive Sleep Apnea Syndrome Associated with
Severe Obesity].
AB - A 41-year-old woman with concomitant severe obesity, obstructive sleep apnea
syndrome, and asthma was scheduled for endoscopic cholecystectomy. She was 165.8
cm tall and weighed 141.2 kg, with BMI of 51.4. We were concerned with difficulty
in ventilation and intubation at the time of anesthesia induction and intra- and
post-operative ventilatory failure. After sedation with fentanyl and droperidol
together with intraoral local anesthesia with lidocaine (Xylocaine Viscous), the
intubating laryngeal mask (ILMA) was inserted while awake, and after the
confirmation of adequate ventilation, the bronchoscope was inserted into the
guide. Although she received no nerve block, she did not choke at the time of
intubation. Because of airway pressure elevation during surgery, volume
controlled ventilation was changed to pressure-controlled ventilation, and,
because of a worsening P/F ratio, the recruitment procedure was performed during
surgery, with a consequent improvement in the ratio. Although the use of the
reservoir and NPPV equipment after extubation was considered, her respiratory
status was stable, and she returned to her room with oxygen mask.
PMID- 26419105
TI - [Desflurane Anesthesia in a Morbidly Obese Patient with Severe Obstructive Sleep
Apnea].
AB - A 33-year-old morbidly obese patient (body mass index = 59.5 kg x m(-2)) with
severe obstructive sleep apnea was scheduled to undergo osteosynthesis of right
radial, ulnar and femoral fractures under general anesthesia. Awake intubation
under conscious sedation using fantanyl and midazolam was performed by the Pentax
AWS Airwayscope. By using desflurane under continuous infusion of remifentanil
0.2-0.5 MUg x kg(-1) x min(-1), BIS values were maintained between 40 and 60
during the surgery. Although duration of surgery was long (430 minutes), the
times from discontinuation of the anesthetic drug to eye opening and extubation
were 82 seconds and 8.5 minutes, respectively. Respiratory depression was minimal
during postoperative period. In this case desflurane was safely used in a
morbidly obese patient with severe obstructive sleep apnea.
PMID- 26419106
TI - [A Case of a Severely Burned Patient with Suspected Takotsubo Cardiomyopathy Who
Underwent Immediate Excision and Skin Grafting under General Anesthesia].
AB - An 88-year-old woman was severely burned on her thigh, leg, arm, buttocks, chest
and abdomen in the bathroom and was emergently admitted to our hospital. The burn
index was 10.8 and the prognostic burn index (PBI) was 99. The reports of
echocardiography, cardiac biomarkers and electrocardiogram showed left
ventricular dysfunction with apical akinesis, which was suspected as Takotsubo
cardiomyopathy. To avoid poor prognosis because of severe PBI, immediate excision
and skin grafting were performed under general anesthesia 23 hours after the burn
onset. More infusion and transfusion than the expected amounts were needed during
anesthesia and the postoperative 4 days because of cardiac failure and septic
shock, which were overcome 14 days after the surgery. The complete early excision
was impossible due to cardiac failure, and that the unexcised burn scar
exacerbated infection and prevented her from survival.
PMID- 26419107
TI - [Anesthetic Management of a Patient Complicated with Marfan Syndrome and
Suffering from Stanford Type A Aortic Dissection during Pregnancy].
AB - We report a case of a 36-year-old woman at 34 weeks of gestation complicated with
Marfan syndrome who underwent Bentall type aortic replacement surgery due to
Stanford type A aortic dissection after undergoing caesarean section. Since this
patient exhibited severe hypotension before coming to the operating room, it was
very difficult to determine whether the cardiac surgery or caesarean section
should be performed first. In this case, the caesarean section was performed
first, followed by Bentall's surgery. Although intra-aortic balloon pumping and
percutaneous cardiopulmonary support were required after weaning from the
cardiopulmonary bypass, she was discharged on post-operative day (POD) 40 and the
baby was discharged on POD 60, without signs of cerebral palsy. Unfortunately,
this patient died on POD 57, due to heart failure. We discuss how to determine
the priority of surgeries for patients who require emergency surgery for
cardiovascular disease during pregnancy.
PMID- 26419108
TI - [Anesthetic Management of an Adult Patient Complicated with Tricuspid Atresia
Maladapted for Fontan Operation Who Underwent Laparoscopic Cholecystectomy].
AB - With the advance of diagnosis and therapeutic management for congenital heart
disease, increasing numbers of the non-cardiac surgery were performed on patients
with post-cardiac surgery, such as the radical operations and Fontan operation.
However, there are adult patients who have not received Fontan operation lacking
indication. We experienced a case of adult surgical patient for laparoscopic
cholecystectomy complicated with tricuspid atresia who was not indicated for
Fontan surgery. A 28-year-old man diagnosed with cholecystolithiasis was
scheduled for laparoscopic cholecystectomy. He had undergone bidirectional Glenn
and Blalock-Taussig shunt, but not undergone Fontan surgery for hypoplasia of the
pulmonary artery and low left ventricular function. To reduce the influence of
intraabdominal pressue on hemodynamics, the insufflations pressure was maintained
at 8 mmHg during pneumoperitoneum. To assist ventricular function, dopamine and
carperitide were administered perioperatively. We should carefully manage such a
patient during perioperative period by understanding the hemodynamic state and
considering the influence of pneumoperitoneum and posture.
PMID- 26419109
TI - [Anesthetic Management for Laparoscopic Surgery in a Very Elderly Patient with
Severe Mitral Regurgitation].
AB - A 90-year-old woman with severe mitral regurgitation underwent laparoscopic
cholecystectomy. In her anesthetic management, we used FloTrac system and
monitored arterial pressure-based cardiac index (CI), stroke volume (SV), and
stroke volume variation (SVV) continuously as the indicators of intraoperative
hemodynamics. Although the blood pressure fluctuated highly in Fowler position
especially, we could control hemodynamics appropriately by intermittent volume
infusion and adjusting administration of cardiovascular agents under monitoring
these indicators. In a very elderly patient with severe mitral regurgitation,
anesthesia and operation may cause severe circulatory disturbances. Therefore, it
is important to select proper monitoring as stated above and maintain
hemodynamics with the utmost care and attention.
PMID- 26419110
TI - [Persistent Disturbance of Consciousness after Clipping of an Unruptured Cerebral
Aneurysm due to Pseudohypoxic Brain Swelling].
AB - A patient developed persistent disturbance of consciousness after uneventful
clipping of an unruptured cerebral aneurysm under general anesthesia.
Pseudohypoxic brain swelling (PHBS) was suspected because computerized tomography
(CT) and magnetic resonance imaging (MRI) revealed diffuse brain swelling,
especially in the bilateral basal ganglia and thalami. Steroid pulse therapy in
addition to antiedematous drugs and anticonvulsant improved the consciousness.
Anesthesiologists should pay attention to PHBS in a case of persistent
disturbance of consciousness after uneventful craniotomy.
PMID- 26419111
TI - [Two Separate Instances of Anesthetic Management in a Patient Initially Diagnosed
with Stiff-person Syndrome].
AB - In this case report, we describe separate instances of general anesthetic
management administered to a patient during treatment for two unrelated
conditions. The patient, a 57-year-old woman who had been experiencing walking
difficulties for about four years, fell down because of muscle rigidity and
spasms and fractured her humerus. She was subsequently diagnosed with stiff
person syndrome. The fracture was treated conservatively, but three weeks later
the alignment of the humerus became worse and the patient was scheduled to
undergo an open reduction and internal fixation under general anesthesia (GA).
Anesthesia was induced using propofol and fentanyl, and rocuronium was given for
the tracheal intubation. The operation was completed successfully while
anesthesia was maintained using sevoflurane and remifentanil without incident
Four months later, the patient developed paraneoplastic syndrome stemming from
breast cancer, and underwent a resection of the cancer under GA. The patient
received propofol for the laryngeal mask insertion, and sevoflurane and
pentazocine for maintenance of anesthesia. She was discharged from the hospital
without any respiratory or airway problems. We used sevoflurane for maintenance
of anesthesia on both occasions, and rocuronium for the first tracheal
intubation. The patient's hemodynamics were stable during the operation. No
prolonged effect of the muscle relaxant or any autonomic reactions were observed.
The patient was fully conscious and in good respiratory condition after both
surgeries, and was extubated in the operating room. There were no perioperative
complications.
PMID- 26419112
TI - [Anesthetic Management for a Patient with Fibromyalgia].
AB - A 22-year-old female with fibromyalgia (FM) was scheduled for tonsillectomy under
general anesthesia. Her medication included pregabalin 300 mg x day(-1) and
dantrolene 50 mg x day(-1). Anesthesia was maintained with sevoflurane
remifentanil-fentanyl. Intravenous injection of fentanyl 20 MUg x hr(-1) and
droperidol 100 MUg x hr(-1) was continued for 24 hours. On the first
postoperative day, she reported that she had slept well and had no pain. There
are some perioperative problems in a patient with FM. Therefore, anesthetic
managements for a patient with FM is worth reporting.
PMID- 26419113
TI - [A Case of Liver Contusion during Spinal Operation for Idiopathic Scoliosis].
AB - A 20-year-old man diagnosed as idiopathic scoliosis with Cobb angle 146 degrees
was scheduled for two-stage operations. Anterior dissection of the thoracic
vertebra in the left lateral decubitus position, and the placement of pedicle
screws in the prone position were performed as the first-stage operation. During
surgery, the patient developed liver contusion with ascites, probably due to
hepatic compression placed between vertebrae and operating table in the prone
position. In the second operation for posterior spinal fusion, the occurrence of
liver contusion was prevented by performing abdominal ultrasonography before and
after surgery, and monitoring AST/ALT during anesthesia as the indicators of
liver contusion. Intraoperative management for organ protection is required
during anesthesia in patients with idiopathic scoliosis associated with thoracic
deformity.
PMID- 26419114
TI - [Perioperative Management of a Patient with Hereditary Angioedema: A Case
Report].
AB - Hereditary angioedema (HAE) is a very rare disease that occurs in about 1 in
50,000 to 150,000 people. HAE is caused by low levels or inproper function of the
plasma protein C1 inhibitor (C1-INH) which regulates activation of the complement
system and the coagulation system. The typical symptom of HAE is regional
swellings without pain nor itching, usually triggered by physical trauma or
emotional stress. Unlike allergic edema, HAE attacks do not respond to
antihistamines, corticosteroids noradrenaline. The swelling attacks against face
and throat are potentially life-threatening, and should be treated as a medical
emergency. We report a patient with HAE who underwent radical cystectomy of the
upper gum under general anesthesia. Because the oral surgery with tracheal
intubation is known to be a risk factor of laryngeal edema in a patient with HAE,
she was given C1-INH before operation to prevent laryngeal edema according to HAE
Guideline 2010 by the Japanese Association for Complement Research. Her pharynx
and larynx were checked with Airwayscope before intubation and with
bronchofiberscope before extubation, but no edema was recognized.
Postoperatively, she was given C1-INH on the next morning again. She was
discharged seven days after operation without any complications.
PMID- 26419115
TI - [Anesthetic Management of a Patient with Langerhans Cell Histiocytosis during
Cesarean section].
AB - Langerhans cell histiocytosis is a rare disease, associated with histiocyte
increases, and granuloma, in various organs. About 160 patients are reported in
Japan. A pregnant patient with a pulmonary Langerhans cell histiocytosis
underwent cesarean section under spinal anesthesia. She had repeated pneumothorax
with bilateral pulmonary cysts rapidly becoming worse during pregnancy. She was
treated with continuous oxygen after 28 weeks of the pregnancy. On 34 weeks of
the pregnancy, spinal anesthesia with 0.5% hyperbaric bupivacaine (2 ml) and
fentanyl (25 MUg) for cesarean section was performed, and provided excellent
analgesia without any side-effects.
PMID- 26419116
TI - [Successful Management of Cardiopulmonary Bypass Using Heparin in a Patient with
Previous History of Heparin-induced Thrombocytopenia].
AB - Anti-coagulant management of cardiopulmonary bypass for the patient complicated
with heparin-induced thrombocytopenia (HIT) is difficult. A woman of late 50's
with a previous history of HIT was scheduled for mitral valve replacement,
tricuspid valvuloplasty and coronary artery bypass graft. We knew that heparin
antibody was negative by serologic and functional assay before the operation.
According to the HIT guideline, we planned to use heparin only during
cardiopulmonary bypass and to use argatroban for other catheters. Although the
platelet count continued decreasing up to the 5th postoperative day unless the
transfusion of platelets, heparin antibody was negative on the first
postoperative day. But, it was thought that HIT would develop from 5 days to 10
days after using heparin. Therefore, we had to examine heparin antibody on the
5th postoperative day at least for the patients with a history of HIT. In the
future, it is important to observe the patient carefully and examine heparin
antibody.
PMID- 26419117
TI - [Treatment of Tension Pneumothorax during Total Right Breast Extirpation and
Reconstruction with a Flap of the Latissimus Dorsi Muscle].
AB - A patient developed tension pneumothorax during surgery. A 56-year-old woman with
right breast cancer and axillary gland metastasis, was to undergo total right
breast extirpation/axillary gland dissection, flap collection from the latissimus
dorsi muscle, and reconstruction with this flap. During total right breast
extirpation/axillary gland dissection, there were no problems, but the arterial
blood oxygen saturation (SpO2) fell after the start of flap collection. After the
start of reconstruction, SpO2 was reduced again. In the right lung field, no
respiratory sound was heard, and chest X-ray showed right tension pneumothorax. A
right thoracic drain was inserted and surgery was completed as scheduled.
Thoracic CT did not reveal any abnormal findings, such as a brassiere, the day
after surgery.
PMID- 26419118
TI - Multi-Level, Multi Time-Scale Fluorescence Intermittency of Photosynthetic LH2
Complexes: A Precursor of Non-Photochemical Quenching?
AB - The light harvesting complex LH2 is a chromoprotein that is an ideal system for
studying protein dynamics via the spectral fluctuations of the emission of its
intrinsic chromophores. We have immobilized these complexes in a polymer film and
studied the fluctuations of the fluorescence intensity from individual complexes
over 9 orders of magnitude in time. Combining time-tagged detection of single
photons with a change-point analysis has allowed the unambigeous identification
of the various intensity levels due to the huge statistical basis of the data
set. We propose that the observed intensity level fluctuations reflect
conformational changes of the protein backbone that might be a precursor of the
mechanism from which nonphotochemical quenching of higher plants has evolved.
PMID- 26419125
TI - Race equality initiative leaves nowhere to hide.
PMID- 26419119
TI - Serum uric acid: a new therapeutic target for nonalcoholic fatty liver disease.
AB - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a major, worldwide
public health problem. NAFLD is recognized as a major cause of liver-related
morbidity and mortality. However, physicians are currently limited by available
treatment options. Recently, numerous studies have reported a correlation between
serum uric acid (SUA) and NAFLD with numerous clinical and experimental studies
demonstrating a significant correlation. This review will focus on the role of
SUA in the development of NAFLD and its potential role as a new target for
therapeutic intervention. AREAS COVERED: This review discusses SUA as a
significant independent factor in the development of NAFLD. Moreover, we
introduce the causal relationship between SUA, metabolic syndrome, and NAFLD. We
discuss two major theories of insulin resistance and inflammasomes as potential
explanations of the mechanistic link between SUA and NAFLD. In addition, we
review current and emerging therapeutic medications to control appropriate SUA
levels. EXPERT OPINION: There is an urgent need to develop novel, safe and
effective therapies for the growing NAFLD epidemic. Reduction of SUA may be a
promising potential treatment for patients with NAFLD. Clinical studies are
required to determine the therapeutic effect of attenuation of hyperuricemia in
humans with NAFLD.
PMID- 26419126
TI - Stepping back into the operating theatres of bygone times.
PMID- 26419127
TI - CPD requirement could remain at 35 hours in bid to reduce costs.
PMID- 26419129
TI - RCN director spearheads campaign to protect paid time off for union reps.
PMID- 26419130
TI - Survey reveals specialist talent not being nurtured. [Corrected].
PMID- 26419128
TI - Staff concerns about pay are 'falling on deaf ears'.
PMID- 26419131
TI - Experts' letter to CNO highlights key issues for safe staffing guidance.
PMID- 26419132
TI - Military nurse closer to home.
PMID- 26419133
TI - Rejected immigration requests causing 'desperate' staff shortages.
PMID- 26419134
TI - A helping hand for Hollywood.
PMID- 26419135
TI - Cambridge trust rated inadequate.
PMID- 26419136
TI - New online resource for budding school nurses.
PMID- 26419138
TI - Why nurses should think twice before using terms of endearment.
PMID- 26419144
TI - Pain.
PMID- 26419145
TI - 'We're beating the BME bias'.
PMID- 26419146
TI - Race and the NHS--a chance for change.
PMID- 26419147
TI - Be aware and beat the odds.
PMID- 26419157
TI - Change4Life.
PMID- 26419158
TI - St John Ambulance First Aid.
PMID- 26419160
TI - Support Alzheimer's patients in petition against cheap headlines.
PMID- 26419161
TI - Short-term pain of union action may bring long-term gain for all.
PMID- 26419164
TI - We can do more to reduce anxiety surrounding breastfeeding.
PMID- 26419162
TI - Direct care target an admirable aim, but Mr Hunt won't help us achieve it.
PMID- 26419165
TI - Snapshot of a career reveals how much the NHS has changed.
PMID- 26419168
TI - How to measure tracheostomy tube cuff pressure.
PMID- 26419169
TI - Disability discrimination in healthcare services and employment.
AB - This article discusses the meaning and philosophical basis of disability
discrimination in health care. It focuses on aspects of language that influence
discourse about disability and affect the experiences of people with
disabilities. Reference is made to the experiences of those who have an autism
spectrum condition, with a specific focus on three NHS employees with Asperger
syndrome, in relation to disability discrimination. The implications for nurses
and nursing are discussed. Recommendations are made for awareness raising and
training.
PMID- 26419170
TI - The PEARL programme: caring for adults living with dementia.
AB - Caring for people living with dementia in care homes requires training in best
dementia care practice and person-centred care. This article describes the main
interventions and processes that have been adopted by Four Seasons Health Care,
an independent provider of residential care homes and care homes with nursing in
the UK, to develop its homes into centres of excellence for dementia care. It
provides an overview of the PEARL (Positively Enriching And enhancing Residents
Lives) programme, which has been found to reduce antipsychotic medication use,
depression scores and pain, and improve patient wellbeing.
PMID- 26419171
TI - Assessing sexual health in mental health service users.
AB - This article encourages the reader to consider sexuality and sexual health as
essential to a full nursing assessment. It discusses the reasons why nurses
should be more open in consultations with mental health service users in regard
to sexual health. A step-by-step model that assists nurses in their interventions
with service users on issues of sexuality is explored, and each stage of the
model is explained. Although predominantly directed at mental health nurses, the
main principles in this article could be adapted and applied to other care
contexts, such as adult nursing.
PMID- 26419172
TI - Concept mapping.
PMID- 26419173
TI - Not so 'hard to reach'.
PMID- 26419175
TI - The long road to equality.
PMID- 26419176
TI - A chance to sell yourself.
PMID- 26419177
TI - Remember to take notes... and ask plenty of questions.
PMID- 26419178
TI - Daunting, yes. But great fun too.
PMID- 26419179
TI - Welcome to our tough, rewarding profession--we're rooting for you.
PMID- 26419180
TI - Budget early for success.
PMID- 26419181
TI - Perfect planning for general practice placements.
PMID- 26419182
TI - A crash course in grief.
PMID- 26419183
TI - RCN Membership: what's in it for you?
PMID- 26419184
TI - Making the most of the student-mentor clinical partnership.
PMID- 26419185
TI - Take a good look at yourself.
PMID- 26419186
TI - 'It is great to work with such a top team'.
PMID- 26419187
TI - Musculoskeletal injuries in physical education versus non-physical education
teachers: a prospective study.
AB - Physical education (PE) teachers have a physically demanding job, putting them at
a considerable risk for musculoskeletal injuries. To structurally develop
tailored injury prevention programmes for PE teachers, a clear understanding of
the extent, characteristics and underlying factors of their musculoskeletal
injuries compared to referents is necessary. Therefore, the current study
prospectively followed 103 PE teachers and 58 non-PE teachers, who registered
musculoskeletal injuries and time of exposure to sports participation during one
school year. Pearson chi(2)-tests and independent samples t-tests determined
significant differences between PE and non-PE teachers regarding demographics and
variables possibly related to injury occurrence. PE teachers had 1.23 and non-PE
teachers 0.78 injuries/teacher/school year. This difference was significantly
different after adjustment for hours spent weekly on intracurricular teaching
during the career and for injury history during the preceding six months (P =
0.009; OR = 0.511; 95% CI = 0.308-0.846). PE teachers' most affected body parts
were the knee and the back. PE teachers had a more extensive injury history (P <
0.001), a higher work- (P < 0.001) and sport index (P < 0.001), practiced more
sports (P < 0.002) and taught more extracurricular sports (P = 0.001). Future
injury prevention programmes should take account for the great injury history and
heavy physical load in PE teachers.
PMID- 26419188
TI - Highly Reliable Silver Nanowire Transparent Electrode Employing Selectively
Patterned Barrier Shaped by Self-Masked Photolithography.
AB - The transparent electrode based on silver nanowire (AgNW) networks is one
promising alternative of indium tin oxide film in particular for advanced
flexible and printable electronics. However, the widespread application of AgNW
electrode is hindered by its poor long-term reliability. Although the reliability
can be improved by applying traditional overcoating layer or the core-shell
structure, the transmittance or conductivity is inevitably undermined. In this
paper, a novel patterned barrier of photoresist in situ assembled on the nanowire
surface realized the reliability enhancement by simply employing AgNWs themselves
as the mask in the photolithography process. The patterned barrier selectively
covered the nanowires, while keeping the high transmittance and conductivity
unchanged and improving the adhesion of AgNW networks on substrate. After 720 h
storage in 85 degrees C/85% relative humidity (RH) environment, the resistance
of electrode with patterned barrier only increased by 0.72 times. This study
proposes a new way, i.e., the in situ patterned barrier containing light
sensitive substance, to selectively protect AgNW networks, which can be expanded
to various metallic networks including nanowires, nanorods, nanocables,
electrospun nanofibers, and so on.
PMID- 26419189
TI - Monitoring the Response of the Human Urinary Metabolome to Brief Maximal Exercise
by a Combination of RP-UPLC-MS and (1)H NMR Spectroscopy.
AB - The delineation of exercise biochemistry by utilizing metabolic fingerprinting
has become an established strategy. We present a combined RP-UPLC-MS and (1)H NMR
strategy, supplemented by photometric assays, to monitor the response of the
human urinary metabolome to short maximal exercise. Seventeen male volunteers
performed two identical sprint sessions on separate days, consisting of three 80
m maximal runs. Using univariate and multivariate analyses, we followed the
fluctuation of 37 metabolites at 1, 1.5, and 2 h postexercise. 2
Hydroxyisovalerate, 2-hydroxybutyrate, 2-oxoisocaproate, 3-methyl-2-oxovalerate,
3-hydroxyisobutyrate, 2-oxoisovalerate, 3-hydroxybutyrate, 2-hydroxyisobutyrate,
alanine, pyruvate, and fumarate increased 1 h postexercise and then returned
toward baseline. Lactate and acetate were higher than baseline at 1 and 1.5 h.
Hypoxanthine and inosine remained above baseline throughout the postexercise
period. Urate decreased at 1 h and increased at 1.5 h before returning to
baseline. Valine, isoleucine, succinate, citrate, trimethylamine, trimethylamine
N-oxide, tyrosine, and formate decreased at 1 h and/or 1.5 h postexercise and
then returned to baseline. Creatinine gradually decreased over the sampling
period. Glycine, 4-aminohippurate, and hippurate remained below baseline
throughout the postexercise period. Our findings show that even one-half minute
of maximal exercise elicited major perturbations in human metabolism, several of
which persisted for at least 2 h.
PMID- 26419190
TI - The importance of triaging in determining the quality of output from high
throughput screening.
PMID- 26419191
TI - Minimal systemic and high faecal exposure to cadazolid in patients with severe
Clostridium difficile infection.
AB - Cadazolid is under development as an oral treatment for Clostridium difficile
infection (CDI), which is the most common infectious cause of antibiotic
associated diarrhoea. Low systemic cadazolid exposures were previously reported
in healthy subjects following both single and multiple oral dosing. The main
objective of this study was to investigate systemic cadazolid exposure in
patients with severe CDI with potential disrupted lining of the gastrointestinal
tract. A single 3000 mg oral dose of cadazolid was administered to six patients
with microbiologically-confirmed severe CDI. Plasma and faeces were collected up
to 144 h post-dose for determination of cadazolid concentrations. Safety
assessments were conducted over the 144-h investigational period. Cadazolid was
well tolerated in patients with severe CDI, with no reported drug-related adverse
events. Cadazolid systemic exposure following a single 3000 mg oral dose was very
low, with a peak plasma concentration (C(max)) of 2.64 ng/mL and an area under
the concentration-time curve (AUC(0-144)) of 125 ng*h/mL. The median peak daily
faecal cadazolid concentration was 5675 times the C. difficile MIC(90) of 0.25
mg/L. In subjects with severe CDI, cadazolid systemic exposure was very low
following a single high oral dose. Cadazolid plasma concentrations were similar
in magnitude to those previously reported for healthy subjects, whereas total
systemic exposure was ca. 5-6 times higher, but was still low. Peak daily faecal
cadazolid concentrations were 5675 times the 0.25 mg/L C. difficile MIC(90), and
on Day 4 five of the six patients presented a daily faecal cadazolid
concentration >=1651 times the MIC(90) [ClinicalTrial.gov ID: NCT02053181].
PMID- 26419192
TI - Spontaneous electric fields in solid carbon monoxide.
AB - Reflection-absorption infrared spectroscopy (RAIRS) is shown to provide a means
of observing the spontelectric phase of matter, the defining characteristic of
which is the occurrence of a spontaneous and powerful static electric field
within a film of material. The presence of such a field is demonstrated here
through the study of longitudinal-transverse optical splitting in RAIR spectra in
films of carbon monoxide, based upon the deposition temperature dependence of
this splitting. Analysis of spectral data, in terms of the vibrational Stark
effect, allows the measurement of the polarization of spontelectric films,
showing for example that solid carbon monoxide at 20 K may maintain a
spontelectric field of 3.78 * 10(7) V m(-1), representing a polarization of 3.34
* 10(-4) cm(-2). We comment on the astrophysical implications of polarized carbon
monoxide ices, on the surface of cosmic grains in star-forming regions.
PMID- 26419193
TI - Psychiatry is a clinical neuroscience, but how do we move the field?
PMID- 26419194
TI - A method comparison of a food frequency questionnaire to measure folate, choline,
betaine, vitamin C and carotenoids with 24-h dietary recalls in women of
reproductive age.
AB - BACKGROUND/OBJECTIVES: The objective of this study was to conduct a method
comparison of a modified food frequency questionnaire (FFQ), designed to estimate
usual dietary intake of selected micronutrients and antioxidants including
folate, choline, betaine, vitamin C and carotenoids (alpha-carotene, beta
carotene, lutein, lycopene and beta-cryptoxanthin) with 24-h dietary recalls (24
HR) in women of reproductive age. SUBJECTS/METHODS: Sixty-four British women of
reproductive age (18-40 years) were recruited in Oxford, UK and provided complete
dietary data for analysis. METHODS: We compared micronutrient estimates from the
FFQ against estimates derived from three multiple-pass, 24-HR interviews, by
evaluating Pearson's correlation coefficients and Bland-Altman plots. RESULTS:
Median intakes of most nutrients were higher when measured by FFQ compared with
24-HR. Strong correlation coefficients were observed for folate (r=0.80) and
choline (r=0.68), whereas moderate correlation coefficients were observed for
vitamin C (0.50) and lycopene (0.43). Weak correlation coefficients were observed
for betaine (0.39) and other carotenoids (r=0.26-0.38). Bland-Altman plots
indicated that there was a large amount of variability in the FFQ estimates of
nutrient intakes compared to those using 24-HR, particularly for carotenoids.
CONCLUSIONS: The findings indicate that this FFQ estimated higher mean intakes
for most nutrients. Pearson's correlation coefficients were comparable with
previous research; however, the Bland-Altman plots suggest a high variability in
mean nutrient estimates between the FFQ and 24-h. We recommend further
investigation of the validity of this FFQ before use.
PMID- 26419195
TI - Body mass index, body fat and risk factor of relapse in anorexia nervosa.
AB - BACKGROUND/OBJECTIVES: Preliminary studies have reported an association between
poor long-term outcome and lower total body fat percentage in weight-restored
inpatients treated for anorexia nervosa (AN). A possible link between poor long
term outcome and higher trunk fat percentage has also been hypothesized. The aim
was to assess the association between percentage and distribution of body fat at
inpatient discharge and the maintenance of normal weight at 1-year follow-up in a
sample of weight-restored females with AN. SUBJECTS/METHODS: Fifty-four short
term weight-restored (body mass index (BMI; in kg/m(2)) ?18.5) adult females with
AN treated in a specialist inpatient unit underwent dual-energy X-ray
absorptiometry to determine total body fat and trunk fat percentages. Patients
were contacted regularly following discharge, and at the end of the year clinical
outcome was dichotomized as either 'full, good or fair' (a group that includes
individuals with a BMI ?18.5 kg/m(2)) or 'poor' (BMI<18.5 kg/m(2)), using the
modified Morgan-Russell criteria. RESULTS: No significant differences were found
between 'full, good or fair' and 'poor' outcome groups in either total body fat
or trunk fat percentages. Only lower BMI at inpatient discharge was associated
with poor clinical outcome in the year following inpatient treatment.
CONCLUSIONS: In short-term weight-restored adult females with AN, BMI, but not
body fat percentage or distribution, at inpatient discharge is associated with
long-term normal weight maintenance.
PMID- 26419196
TI - Unprocessed red meat and processed meat consumption and risk of stroke in the
Spanish cohort of the European Prospective Investigation into Cancer and
Nutrition (EPIC).
AB - BACKGROUND/OBJECTIVES: High intakes of unprocessed red or processed meat may
increase the risk of stroke. We aimed to examine the association between
unprocessed red meat, processed meat and total red meat consumption and risk of
total stroke and ischaemic stroke. SUBJECTS/METHODS: Cox proportional hazards
regression analyses were conducted based on the data for 41,020 men and women
aged 29-69 years at baseline. RESULTS: During a mean follow-up of 13.8 years, 674
incident cases of stroke (531 ischaemic strokes, 79 haemorrhagic strokes, 42
subarachnoid haemorrhages and 22 mixed or unspecified events) were identified.
After multiple adjustment, unprocessed red meat, processed meat and total red
meat consumption were not correlated with incidence of total stroke or ischaemic
stroke in either men or women. The hazard ratios (HRs) for unprocessed red meat
and processed meat and risk of total stroke comparing the highest with the lowest
quintiles were, respectively, 0.81 (95% confidence interval (CI) 0.54-1.21; P
trend=0.15) and 0.92 (95% CI 0.64-1.32; P-trend=0.82) in men and 1.21 (95% CI
0.79-1.85; P-trend=0.10) and 0.81 (95% CI 0.51-1.27; P-trend=0.17) in women. The
HRs for unprocessed red meat and processed meat and risk of ischaemic stroke
were, respectively, 0.80 (95% CI 0.51-1.25; P-trend=0.51) and 0.86 (95% CI 0.57
1.29; P-trend=0.77) in men and 1.24 (95% CI 0.74-2.05; P-trend=0.13) and 0.82
(95% CI 0.47-1.42; P-trend=0.31) in women. CONCLUSIONS: In the Spanish European
Prospective Investigation into Cancer and Nutrition (EPIC) cohort, unprocessed
red meat and processed meat consumption were not associated with risk of stroke
in men or women.
PMID- 26419197
TI - Breast milk composition and infant nutrient intakes during the first 12 months of
life.
AB - BACKGROUND/OBJECTIVES: The objective of this study was to quantify human milk
supply and intake of breastfed infants up to age 12 months. In addition, human
milk composition was quantified per energetic macronutrient and fatty-acid
composition in a subsample of lactating mothers. SUBJECTS/METHODS: One hundred
and seventy-four Italian breastfed children were followed using test-weighing and
3-day food protocols from birth to age 12 months. From a subsample of 30 mothers
breast milk samples were collected at child ages one (T1), two (T2), three (T3)
and six (T6) months, and were analyzed for the amount of protein, digestible
carbohydrates, total lipids and fatty-acid composition. RESULTS: One hundred and
forty-two (82%) filled in at least one 3-day food protocol within the first 12
months of life and complied with test-weighing of all milk feeds. The number of
valid food protocols declined from 126 infants at 1 month to 77 at 12 months of
age. Only galactose, non-protein nitrogen and protein decreased significantly
from age 1 to age 6 months of lactation. Maternal body mass index and age
affected fatty-acid levels in human milk. Median human milk intake decreased from
625 ml at T1, over 724 ml at T3 to 477 ml/day at T6. Average energy and %energy
from protein intake per day increased from 419 kcal (s.d. 99) and 8.4% (1.0) at
T1, respectively, to 860 kcal (145) and 16.1% (2.6) at T12. CONCLUSIONS: These
data provide a reference range of nutrient intakes in breastfed infants and may
provide guidance for defining optimal nutrient intakes for infants that cannot be
fully breastfed.
PMID- 26419198
TI - Similar protective immunity induced by an inactivated enterovirus 71 (EV71)
vaccine in neonatal rhesus macaques and children.
AB - During the development of enterovirus 71 (EV71) inactivated vaccine for
preventing human hand, foot and mouth diseases (HFMD) by EV71 infection, an
effective animal model is presumed to be significant and necessary. Our previous
study demonstrated that the vesicles in oral regions and limbs potentially
associated with viremia, which are the typical manifestations of HFMD, and
remarkable pathologic changes were identified in various tissues of neonatal
rhesus macaque during EV71 infection. Although an immune response in terms of
neutralizing antibody and T cell memory was observed in animals infected by the
virus or stimulated by viral antigen, whether such a response could be considered
as an indicator to justify the immune response in individuals vaccinated or
infected in a pandemic needs to be investigated. Here, a comparative analysis of
the neutralizing antibody response and IFN-gamma-specific T cell response in
vaccinated neonatal rhesus macaques and a human clinical trial with an EV71
inactivated vaccine was performed, and the results showed the identical tendency
and increased level of neutralizing antibody and the IFN-gamma-specific T cell
response stimulated by the EV71 antigen peptide. Importantly, the clinical
protective efficacy against virus infection by the elicited immune response in
the immunized population compared with the placebo control and the up-modulated
gene profile associated with immune activation were similar to those in infected
macaques. Further safety verification of this vaccine in neonatal rhesus macaques
and children confirmed the potential use of the macaque as a reliable model for
the evaluation of an EV71 candidate vaccine.
PMID- 26419199
TI - Enhancement of long-lasting immunoprotective effect against Androctonus australis
hector envenomation using safe antigens: Comparative role of MF59 and Alum
adjuvants.
AB - Envenomation is a public health problem in many regions of the world. The only
available treatment is the serotherapy that has limited efficiency due to the
delay of its administration. The goal of this study is to provide a new and more
efficient alternative to this treatment. A comparative study of the effects of
two adjuvants in their ability to enhance the efficiency of the detoxified and
safe antigens to produce a long lasting immunoprotection is undertaken using
Aluminum Hydroxide adjuvant (Alum) or the water-in-oil MF59 adjuvant mixed with
Androctonus australis hector (Aah) detoxified venom, and compare their effects on
the immune system. Immunization schedule was performed with two groups of
rabbits, which were injected with attenuated venom and Alum or MF59 adjuvant
preparations, once a month during three months. Blood samples were collected each
week for cell count, evaluation of myeloperoxidase (MPO) and eosinoperoxydase
(EPO) activities and antibody titer. After four months from the last
immunization, rabbits were challenged with increased doses of native Aah venom.
Results showed that MF59 effect was immediate in the first 24h post-immunization
by activating the recruitment of lymphocytes, monocytes and neutrophils, while
Alum adjuvant effect seems to be delayed, and appeared in the second week after
immunization. An important cell infiltration was observed with Alum preparation,
due to its specific local depot effect. However, immunized animals with MF59
preparation challenged with the native venom showed a protective effect against
its toxicity until 6 LD50 compared to those immunized with Alum preparation which
are only protected at 4 LD50. One week after challenge, only immunized animals
with Alum preparation present an increase in cell infiltration, MPO and EPO
activities. These results are correlated with the ability of MF59 adjuvant to
induce a potent immunoprotective effect against Aah venom compared to Alum
adjuvant.
PMID- 26419201
TI - Mechanism-Driven Elaboration of an Enantioselective Bromocyclopropanation
Reaction of Allylic Alcohols.
AB - A stereoselective bromocyclopropanation of allylic alcohols using
dibromomethylzinc bromide is described. Spectroscopic studies to monitor the
formation of transient intermediates not only led to the development of a more
atom-economical halocyclopropanation reaction, but also highlighted the unique
role of ether additives in the process. The desired bromo-substituted
cyclopropanes were isolated in high yields and excellent diastereo- as well as
enantioselectivities using readily available reagents.
PMID- 26419200
TI - Simultaneous MR imaging for tissue engineering in a rat model of stroke.
AB - In situ tissue engineering within a stroke cavity is gradually emerging as a
novel therapeutic paradigm. Considering the varied lesion topology within each
subject, the placement and distribution of cells within the lesion cavity is
challenging. The use of multiple cell types to reconstruct damaged tissue
illustrates the complexity of the process, but also highlights the challenges to
provide a non-invasive assessment. The distribution of implanted cells within the
lesion cavity and crucially the contribution of neural stem cells and endothelial
cells to morphogenesis could be visualized simultaneously using two paramagnetic
chemical exchange saturation transfer (paraCEST) agents. The development of
sophisticated imaging methods is essential to guide delivery of the building
blocks for in situ tissue engineering, but will also be essential to understand
the dynamics of cellular interactions leading to the formation of de novo tissue.
PMID- 26419203
TI - Foxp3-expressing sensitized Teff cells prolong survival of corneal allograft in
corneal allograft transplantation mouse model.
AB - OBJECTIVE: The study aimed to investigate whether Foxp3-expressing sensitized
Teff cells could inhibit allograft rejection in corneal allograft transplantation
mouse model. METHODS: Foxp3-expressing sensitized Teff cells were constructed by
transfection of retroviral expression plasmid expressing Foxp3 into the sensi
Teff cells from a Balb/c mouse immunized by C57BL/6(H2b) mouse splenocytes.
Balb/c mice were randomly divided into 5 groups: Four groups received tail vein
injection of Foxp3-expressing sensitized Teff cells, or Foxp3-expressing Teff
cells, or Treg cells or no intervention 1 day prior to corneal allograft
transplantation. C57BL/6(H2b) was the donor mouse. The last group received
corneal autograft transplantation. Corneal allograft survival time and percentage
of CD4(+) T cells were detected. ELISPOT and Footpad swelling test were used to
measure IL-2 and IFN-gamma, and delayed-type hypersensitivity (DTH) response,
respectively. RESULTS: Mice that had received an injection of Foxp3-expressing
sensitized T cells prior to an allograft corneal transplantation, showed
significantly longer survival time of corneal allograft, decreased percentage of
CD4(+) T cells, IL-2 and IFN-gamma, and alleviated footpad swelling than the mice
that had received either Foxp3-Teff or Treg cells. CONCLUSION: Foxp3-sensi-Teff
cell treatment that prolongs corneal allograft survival in the mouse model, might
partly through suppressing CD4(+) T cells, IL-2 and IFN-gamma.
PMID- 26419204
TI - Enhanced light absorption by mixed source black and brown carbon particles in UK
winter.
AB - Black carbon (BC) and light-absorbing organic carbon (brown carbon, BrC) play key
roles in warming the atmosphere, but the magnitude of their effects remains
highly uncertain. Theoretical modelling and laboratory experiments demonstrate
that coatings on BC can enhance BC's light absorption, therefore many climate
models simply assume enhanced BC absorption by a factor of ~1.5. However, recent
field observations show negligible absorption enhancement, implying models may
overestimate BC's warming. Here we report direct evidence of substantial field
measured BC absorption enhancement, with the magnitude strongly depending on BC
coating amount. Increases in BC coating result from a combination of changing
sources and photochemical aging processes. When the influence of BrC is accounted
for, observationally constrained model calculations of the BC absorption
enhancement can be reconciled with the observations. We conclude that the
influence of coatings on BC absorption should be treated as a source and
regionally specific parameter in climate models.
PMID- 26419205
TI - Research of methods to detect genomic mutations induced by CRISPR/Cas systems.
AB - The indel-forming non-homologous end joining (NHEJ) pathway repairs double strand
breaks in mammalian genomes, resulting in mutation formation following genome
editing. Common techniques employed to identify these mutations include the
amplified fragment length polymorphism (AFLP) and SURVEYOR assays, which are time
consuming, laborious, and only offer a low level of sensitivity. An alternative
to these approaches, which is examined in this study, is based on the
quantitative PCR high-resolution melting (qPCR-HRM) curve analysis technique and
offers simple implementation, is capable of handling large sample sizes, takes no
more than 90 min, and produces sensitive results. Using the newly discovered RNA
guided CRISPR/Cas systems, the IL2RG and EMX1 genes were edited in the human 293T
cell line in order to compare the mutation detection accuracies of the
aforementioned methods. Genomic mutations were simulated by mixing mutated DNA
fragments with normal fragments along a concentration gradient. The results of
this comparative study showed that the HRM approach was both reproducible and
accurate.
PMID- 26419206
TI - Psychotic experiences and risk of self-injurious behaviour in the general
population: a systematic review and meta-analysis.
AB - BACKGROUND: Recent studies suggest that psychotic experiences (PE) in the general
population are associated with an increased risk of self-injurious behaviour.
Both the magnitude of this association and the level of adjustment for
confounders vary among studies. A meta-analysis was performed to integrate the
available evidence. The influence of possible confounders, including variably
defined depression, was assessed. METHOD: A systematic review and meta-analysis
was conducted including general population studies reporting on the risk of self
injurious behaviour in individuals with PE. Studies were identified by a
systematic search strategy in Pubmed, PsycINFO and Embase. Reported effect sizes
were extracted and meta-analytically pooled. RESULTS: The risk of self-injurious
behaviour was 3.20 times higher in individuals with PE compared with those
without. Subanalyses showed that PE were associated with self-harm, suicidal
ideation as well as suicidal attempts. All studies had scope for considerable
residual confounding; effect sizes adjusted for depression were significantly
smaller than effect sizes unadjusted for depression. In the longitudinal studies,
adjustment for psychopathology resulted in a 74% reduction in excess risk.
CONCLUSIONS: PE are associated with self-injurious behaviour, suggesting they
have potential as passive markers of suicidality. However, the association is
confounded and several methodological issues remain, particularly how to separate
PE from the full range of connected psychopathology in determining any specific
association with self-injurious behaviour. Given evidence that PE represent an
indicator of severity of non-psychotic psychopathology, the association between
PE and self-injurious behaviour probably reflects a greater likelihood of self
injurious behaviour in more severe states of mental distress.
PMID- 26419207
TI - Assessment and care of visuospatial disorientation in a mixed dementia patient: a
case study using objective measurements.
AB - We present a case of a mixed dementia patient with visuospatial disorientation
and a developmental disability. The patient was a 69-year-old man who was
hospitalized for resistance to care, wandering, and a sleep disorder. He was in
the advanced stages of dementia and had severe visual impairment due to
cataracts. We used an integrated circuit monitoring system and Actiwatch to
measure the distance moved per day and sleep-rest cycle, respectively. We
administered a coloured paper test to assess the colour most easily recognized by
the patient, which was red. We found that displaying his name in large red
letters by his door enabled the patient to read his name. We also moved him to a
private room next to the day room. The distance moved per day decreased
significantly after the implementation of the care plan. However, after the room
change, large urine spills were often observed in the bathroom, indicating
visuospatial problems. We placed red adhesive tape onto the toilet bowl to make
it more visible, which solved the urine spill problem. This case study
demonstrates the efficacy of using simple assessment techniques to identify the
remaining abilities of a dementia patient and taking simple steps to address the
behavioural and psychological symptoms of dementia.
PMID- 26419208
TI - Nucleic-acid recognition interfaces: how the greater ability of RNA duplexes to
bend towards the surface influences electrochemical sensor performance.
AB - The influence of RNA versus DNA on the performance of electrochemical biosensors
where redox-labelled nucleic acid duplexes bend towards the electrode surface has
been assessed. Faster electron transfer was observed for duplexes containing RNA,
suggesting duplexes with RNA are more flexible. These data are of particular
importance for microRNA biosensors.
PMID- 26419209
TI - Millisecond single-molecule localization microscopy combined with convolution
analysis and automated image segmentation to determine protein concentrations in
complexly structured, functional cells, one cell at a time.
AB - We present a single-molecule tool called the CoPro (concentration of proteins)
method that uses millisecond imaging with convolution analysis, automated image
segmentation and super-resolution localization microscopy to generate robust
estimates for protein concentration in different compartments of single living
cells, validated using realistic simulations of complex multiple compartment cell
types. We demonstrate its utility experimentally on model Escherichia coli
bacteria and Saccharomyces cerevisiae budding yeast cells, and use it to address
the biological question of how signals are transduced in cells. Cells in all
domains of life dynamically sense their environment through signal transduction
mechanisms, many involving gene regulation. The glucose sensing mechanism of S.
cerevisiae is a model system for studying gene regulatory signal transduction. It
uses the multi-copy expression inhibitor of the GAL gene family, Mig1, to repress
unwanted genes in the presence of elevated extracellular glucose concentrations.
We fluorescently labelled Mig1 molecules with green fluorescent protein (GFP) via
chromosomal integration at physiological expression levels in living S.
cerevisiae cells, in addition to the RNA polymerase protein Nrd1 with the
fluorescent protein reporter mCherry. Using CoPro we make quantitative estimates
of Mig1 and Nrd1 protein concentrations in the cytoplasm and nucleus compartments
on a cell-by-cell basis under physiological conditions. These estimates indicate
a ~4-fold shift towards higher values in the concentration of diffusive Mig1 in
the nucleus if the external glucose concentration is raised, whereas equivalent
levels in the cytoplasm shift to smaller values with a relative change an order
of magnitude smaller. This compares with Nrd1 which is not involved directly in
glucose sensing, and which is almost exclusively localized in the nucleus under
high and low external glucose levels. CoPro facilitates time-resolved
quantification of protein concentrations in single functional cells, and enables
the distributions of concentrations across a cell population to be measured. This
could be useful in investigating several cellular processes that are mediated by
proteins, especially where changes in protein concentration in a single cell in
response to changes in the extracellular chemical environment are subtle and
rapid and may be smaller than the variability across a cell population.
PMID- 26419210
TI - Evaluation of fracture resistance of endodontically treated teeth restored with
composite resin along with fibre insertion in different positions in vitro.
AB - This study was carried out to compare the different techniques of placement of
polyethylene fibre (Ribbond) on reinforcement of endodontically treated teeth
with MOD cavities in vitro. Forty extracted human premolars were randomly
assigned to four groups (n = 10). Teeth in Groups I-IV received root canal
treatment and a MOD cavity preparation, with gingival cavosurface margin 1.5 mm
in coronal to cementoenamel junction. Group I served as no fibre group, Group II
as occlusal fibre group, Group III as base fibre group and Group IV as dual-fibre
group (occlusal and base both). Subsequent to restoring with composite resin and
thermocycling, a vertical compressive force was applied at a cross-head speed of
0.5 mm min(-1) using universal testing machine until fracture. Data were analysed
using one-way analysis of variance and Tukey's post hoc tests. Fracture
resistance was significantly highest in dual-fibre group (P < 0.001) as compared
with other groups. The highest favourable fracture rate was observed in the base
fibre group (70%). This study concluded that the use of polyethylene fibre
inserted over or under the restoration significantly increased the fracture
strength of the root canal-treated teeth and maximum fracture resistance was
observed when cavity was restored using dual-fibre technique.
PMID- 26419211
TI - Enhanced detection of quantum dots labeled protein by simultaneous bismuth
electrodeposition into microfluidic channel.
AB - In this study, we propose an electrochemical immunoassay into a disposable
microfluidic platform, using quantum dots (QDs) as labels and their enhanced
detection using bismuth as an alternative to mercury electrodes. CdSe@ZnS QDs
were used to tag human IgG as a model protein and detected through highly
sensitive stripping voltammetry of the dissolved metallic component (cadmium in
our case). The modification of the screen printed carbon electrodes (SPCEs) was
done by a simple electrodeposition of bismuth that was previously mixed with the
sample containing QDs. A magneto-immunosandwich assay was performed using a
micromixer. A magnet placed at its outlet in order to capture the magnetic beads
used as solid support for the immunoassay. SPCEs were integrated at the end of
the channel as detector. Different parameters such as bismuth concentration, flow
rate, and incubation times, were optimized. The LOD for HIgG in presence of
bismuth was 3.5 ng/mL with a RSD of 13.2%. This LOD was about 3.3-fold lower than
the one obtained without bismuth. Furthermore, the sensitivity of the system was
increased 100-fold respect to experiments carried out with classical screen
printed electrodes, both in presence of bismuth.
PMID- 26419212
TI - Intergenomic interactions between mitochondrial and Y-linked genes shape male
mating patterns and fertility in Drosophila melanogaster.
AB - Under maternal inheritance, mitochondrial genomes are prone to accumulate
mutations that exhibit male-biased effects. Such mutations should, however, place
selection on the nuclear genome for modifier adaptations that mitigate
mitochondrial-incurred male harm. One gene region that might harbor such
modifiers is the Y-chromosome, given the abundance of Y-linked variation for male
fertility, and because Y-linked modifiers would not exert antagonistic effects in
females because they would be found only in males. Recent studies in Drosophila
revealed a set of nuclear genes whose expression is sensitive to allelic
variation among mtDNA- and Y-haplotypes, suggesting these genes might be entwined
in evolutionary conflict between mtDNA and Y. Here, we test whether genetic
variation across mtDNA and Y haplotypes, sourced from three disjunct populations,
interacts to affect male mating patterns and fertility across 10 days of early
life in D. melanogaster. We also investigate whether coevolved mito-Y
combinations outperform their evolutionarily novel counterparts, as predicted if
the interacting Y-linked variance is comprised of modifier adaptations. Although
we found no evidence that coevolved mito-Y combinations outperformed their novel
counterparts, interactions between mtDNA and Y-chromosomes affected male mating
patterns. These interactions were dependent on male age; thus male reproductive
success was shaped by G * G * E interactions.
PMID- 26419213
TI - Evidence of a dissociation pattern in default mode subnetwork functional
connectivity in schizophrenia.
AB - The default mode network (DMN) is suggested to play a pivotal role in
schizophrenia; however, the dissociation pattern of functional connectivity of
DMN subsystems remains uncharacterized in this disease. In this study, resting
state fMRI data were acquired from 55 schizophrenic patients and 53 matched
healthy controls. DMN connectivity was estimated from time courses of independent
components. The lateral DMN exhibited decreased connectivity with the unimodal
sensorimotor cortex but increased connectivity with the heteromodal association
areas in schizophrenics. The increased connectivity between the lateral DMN and
right control network was significantly correlated with negative and anergia
factor scores in the schizophrenic patients. The anterior and posterior DMNs
exhibited increased and decreased connectivity with the right control and lateral
visual networks, respectively, in schizophrenics. The altered DMN connectivity
may underlie the hallucinations, delusions, thought disturbances, and negative
symptoms involved in schizophrenia. Furthermore, DMN connectivity patterns could
be used to differentiate patients from controls with 76.9% accuracy. These
findings may shed new light on the distinct role of DMN subsystems in
schizophrenia, thereby furthering our understanding of the pathophysiology of
schizophrenia. Elucidating key disease-related DMN subsystems is critical for
identifying treatment targets and aiding in the clinical diagnosis and
development of treatment strategies.
PMID- 26419214
TI - How Sensitive is the Amide I Vibration of the Polypeptide Backbone to Electric
Fields?
AB - Site-selective isotopic labeling of amide carbonyls offers a nonperturbative
means to introduce a localized infrared probe into proteins. Although this
strategy has been widely used to investigate various biological questions, the
dependence of the underlying amide I vibrational frequency on electric fields (or
Stark tuning rate) has not been fully determined, which prevents it from being
used in a quantitative manner in certain applications. Herein, through the use of
experiments and molecular dynamics simulations, the Stark tuning rate of the
amide I vibration of an isotopically labeled backbone carbonyl in a transmembrane
alpha-helix is determined to be approximately 1.4 cm(-1) /(MV/cm). This result
provides a quantitative basis for using this vibrational model to assess local
electric fields in proteins, among other applications. For instance, by using
this value, we are able to show that the backbone region of a dipeptide has a
surprisingly low dielectric constant.
PMID- 26419215
TI - Effects of therapeutic positioning on vital parameters in patients with central
neurological disorders: a randomised controlled trial.
AB - AIMS AND OBJECTIVES: To investigate the effects of positioning on heart rate,
breathing frequency and blood pressure in postacute, severely disabled patients
with central neurological disorders. BACKGROUND: Positioning patients is part of
the regular nursing routine in the care for severely disabled patients.
Positioning can be done in a conventional way or in Lagerung in Neutralstellung
(Engl.: positioning in neutral), which has recently been shown to have better
effects on the passive range of motion and comfort than conventional positioning.
While it is thought that positioning influences vital parameters, so far no study
has investigated this for a clinically relevant observation period, and no study
has compared different positioning concepts in this respect. DESIGN: A
multicentre, randomised, controlled, single-blind clinical trial. METHODS: Two
hundred and eighteen patients were randomly assigned to positioning in neutral or
conventional positioning. For two hours, they were lying in one of five positions
(supine, 30 degrees and 90 degrees side lying on the right or left side)
according to the respective positioning concept. Heart rate, breathing frequency
and blood pressure were measured before and after positioning in a supine lying
position (i.e. not positioned according to any concept). It was investigated if
the interventions influence vital parameters and whether there are differences
between positioning in neutral and conventional positioning, or between the
different positions. RESULTS: In neither of the groups did heart rate, breathing
frequency and blood pressure change significantly after the intervention compared
to before (p <= 0.01). CONCLUSION: Positioning does not influence heart rate,
breathing frequency and blood pressure when patients are lying for a clinically
feasible length of two hours. RELEVANCE TO CLINICAL PRACTICE: This study shows
that nurses can apply both positioning concepts according to their patients'
preferences or to address problems like pressure sore prevention. There is no
risk of influencing basic vital parameters.
PMID- 26419216
TI - Seed priming with polyethylene glycol regulating the physiological and molecular
mechanism in rice (Oryza sativa L.) under nano-ZnO stress.
AB - The present study was designed to highlight the impact of seed priming with
polyethylene glycol on physiological and molecular mechanism of two cultivars of
Oryza sativa L. under different levels of zinc oxide nanorods (0, 250, 500 and
750 mg L(-1)). Plant growth parameters were significantly increased in seed
priming with 30% PEG under nano-ZnO stress in both cultivars. Whereas, this
increase was more prominent in cultivar Qian You No. 1 as compared to cultivar
Zhu Liang You 06. Significant increase in photosynthetic pigment with PEG priming
under stress. Antioxidant enzymes activities of superoxide dismutase (SOD),
peroxidase (POD) and catalase (CAT) as well as malondialdehyde (MDA) contents
were significantly reduced with PEG priming under nano-ZnO stress. Gene
expression analysis also suggested that expression of APXa, APXb, CATa, CATb,
CATc, SOD1, SOD2 and SOD3 genes were down regulated with PEG priming as compared
to non-primed seeds under stress. The ultrastructural analysis showed that leaf
mesophyll and root cells were significantly damaged under nano-ZnO stress in both
cultivars but the damage was prominent in Zhu Liang You 06. However, seed priming
with PEG significantly alleviate the toxic effects of nano-ZnO stress and
improved the cell structures of leaf and roots in both cultivars.
PMID- 26419217
TI - Prospective food diaries demonstrate breastfeeding characteristics in a UK birth
cohort.
AB - Breastfeeding duration and exclusive breastfeeding rates are universally below
those recommended by World Health Organization. Due to limitations and challenges
associated with researching breastfeeding characteristics, the times when
exclusivity is likely to be lost and when women are most likely to discontinue
breastfeeding have not yet been identified. Prospective food diaries allow
reliable description of the dynamics of breastfeeding to be made to help identify
these key time periods. Food diaries detailing intake from birth until the
cessation of breastfeeding were analysed for 718 infants recruited into a
national arm of an international multicentre birth cohort study (EuroPrevall).
Analyses included linear regression analysis and Kaplan-Meier time course
analysis. Breastfeeding and exclusive breastfeeding cessation rates for younger
mothers (<25 years) are high in the first few weeks after delivery but slow
markedly in the period 10-12 weeks after delivery. Cessation rates are consistent
from 0 to 26 weeks in older mothers. This difference in feeding patterns led to
significant differences between the two different age groups at 26 weeks for
breastfeeding (P = 0.006) and exclusive breastfeeding at 8 weeks (P = 0.009).
Forty-nine per cent of younger mothers (<25 years) stopped breastfeeding before
their infant was 3 weeks old. To increase breastfeeding duration, further work is
required to investigate the attitudes and perceptions associated with such high
breastfeeding cessation rates in younger mothers during these very early post
natal weeks.
PMID- 26419218
TI - A familial pericentric inversion of chromosome 11 associated with a microdeletion
of 163 kb and microduplication of 288 kb at 11p13 and 11q22.3 without aniridia or
eye anomalies.
AB - Interstitial deletions of 11p13 involving MPPED2, DCDC5, DCDC1, DNAJC24, IMMP1L,
and ELP4 are previously reported to have downstream transcriptional effects on
the expression of PAX6, due to a downstream regulatory region (DRR). Currently,
no clear genotype-phenotype correlations have been established allowing for
conclusive information regarding the exact location of the PAX6 DRR, though its
location has been approximated in mouse models to be within the Elp4 gene. Of the
clinical reports currently published examining patients with intact PAX6 genes
but harboring deletions identified in genes downstream of PAX6, 100% indicate
phenotypes which include aniridia, whereas approximately half report additional
eye deformities, autism, or intellectual disability. In this clinical report, we
present a 12-year-old male patient, his brother, and mother with pericentric
inversions of chromosome 11 associated with submicroscopic interstitial deletions
of 11p13 and duplications of 11q22.3. The inversions were identified by standard
cytogenetic analysis; microarray and FISH detected the chromosomal imbalance. The
patient's phenotype includes intellectual disability, speech abnormalities, and
autistic behaviors, but interestingly neither the patient, his brother, nor
mother have aniridia or other eye anomalies. To the best of our knowledge, these
findings in three family members represent the only reported cases with 11p13
deletions downstream of PAX6 not demonstrating phenotypic characteristics of
aniridia or abnormal eye development. Although none of the deleted genes are
obvious candidates for the patient's phenotype, the absence of aniridia in the
presence of this deletion in all three family members further delineates the
location of the DRR for PAX6.
PMID- 26419220
TI - Children with PIMD in interaction with peers with PIMD or siblings.
AB - BACKGROUND: The complex disabilities of children with profound intellectual and
multiple disabilities (PIMD) impede their presentation of peer directed
behaviours. Interactions with typically developing peers have been observed to be
more frequent than those with peers with PIMD. The typically developing peers
with whom people with PIMD have frequent contact are their siblings. In this
study, the amount of peer directed behaviours was compared between an interaction
with a sibling and an interaction with a peer with PIMD. In addition, the
attention directing strategies of the siblings, and how these affect the
presentation of peer directed behaviours, were examined. METHOD: Thirteen
children and young people with PIMD, who had a typically developing sibling, were
identified. For each of these thirteen children, a peer with PIMD and a sibling
were selected. The child with PIMD was observed together with a peer with PIMD
and together with a sibling. In both conditions, video observations were
conducted. A coding scheme for the peer directed behaviours of the children and
young people with PIMD and a coding scheme for the attention directing behaviours
of the siblings were used. Descriptive, comparative and sequential analyses were
conducted. RESULTS: Significantly, more peer directed behaviours of the children
with PIMD were observed in the condition with the sibling (30.76%) compared with
that of the condition with the peer with PIMD (13.73%). The siblings presented
attention directing behaviours in 30% of the time; the most frequently used was
nonverbal behaviour. When the siblings presented a combination of verbal and
nonverbal attention directing behaviours, they elicited multiple peer directed
behaviours in the children and young people with PIMD. CONCLUSIONS: Persons with
PIMD interact more with their siblings compared with their peers with PIMD.
Interacting with siblings may probably be more motivating and encouraging.
Presenting a combination of verbal and nonverbal behaviours attracts more
attention of the persons with PIMD.
PMID- 26419219
TI - PucC and LhaA direct efficient assembly of the light-harvesting complexes in
Rhodobacter sphaeroides.
AB - The mature architecture of the photosynthetic membrane of the purple phototroph
Rhodobacter sphaeroides has been characterised to a level where an atomic-level
membrane model is available, but the roles of the putative assembly proteins LhaA
and PucC in establishing this architecture are unknown. Here we investigate the
assembly of light-harvesting LH2 and reaction centre-light-harvesting1-PufX (RC
LH1-PufX) photosystem complexes using spectroscopy, pull-downs, native gel
electrophoresis, quantitative mass spectrometry and fluorescence lifetime
microscopy to characterise a series of lhaA and pucC mutants. LhaA and PucC are
important for specific assembly of LH1 or LH2 complexes, respectively, but they
are not essential; the few LH1 subunits found in DeltalhaA mutants assemble to
form normal RC-LH1-PufX core complexes showing that, once initiated, LH1 assembly
round the RC is cooperative and proceeds to completion. LhaA and PucC form
oligomers at sites of initiation of membrane invagination; LhaA associates with
RCs, bacteriochlorophyll synthase (BchG), the protein translocase subunit YajC
and the YidC membrane protein insertase. These associations within membrane
nanodomains likely maximise interactions between pigments newly arriving from
BchG and nascent proteins within the SecYEG-SecDF-YajC-YidC assembly machinery,
thereby co-ordinating pigment delivery, the co-translational insertion of LH
polypeptides and their folding and assembly to form photosynthetic complexes.
PMID- 26419221
TI - Functional characterization of a glucosyltransferase gene, LcUFGT1, involved in
the formation of cyanidin glucoside in the pericarp of Litchi chinensis.
AB - Anthocyanins generate the red color in the pericarp of Litchi chinensis. UDP
glucose: flavonoid 3-O-glycosyltransferase (UFGT, EC. 2.4.1.91) stabilizes
anthocyanidin by attaching sugar moieties to the anthocyanin aglycone. In this
study, the function of an UFGT gene involved in the biosynthesis of anthocyanin
was verified through heterologous expression and virus-induced gene silencing
assays. A strong positive correlation between UFGT activity and anthocyanin
accumulation capacity was observed in the pericarp of 15 cultivars. Four putative
flavonoid 3-O-glycosyltransferase-like genes, designated as LcUFGT1 to LcUFGT4,
were identified in the pericarp of litchi. Among the four UFGT gene members, only
LcUFGT1 can use cyanidin as its substrate. The expression of LcUFGT1 was parallel
with developmental anthocyanin accumulation, and the heterologously expressed
protein of LcUFGT1 displayed catalytic activities in the formation of
anthocyanin. The LcUFGT1 over-expression tobacco had darker petals and pigmented
filaments and calyxes resulting from higher anthocyanin accumulations compared
with non-transformed tobacco. In the pericarp with LcUFGT1 suppressed by virus
induced gene silencing, pigmentation was retarded, which was well correlated with
the reduced-LcUFGT1 transcriptional activity. These results suggested that the
glycosylation-related gene LcUFGT1 plays a critical role in red color formation
in the pericarp of litchi.
PMID- 26419222
TI - Habitat-associated skew of clone abundance in the Pseudomonas aeruginosa
population.
AB - The population structure of the cosmopolitan Pseudomonas aeruginosa was
investigated by genotyping 2921 isolates from 1448 independent habitats with a
custom-made 58 binary marker microarray. Of 323 identified clone types, 109
clones made up 82% of the population. The 20 most frequent clones had an absolute
share of 44% indicating that the P. aeruginosa population is dominated by few
epidemic clonal complexes. The frequency distribution of common clones was
different between inanimate habitats and human niches. The three most abundant
clones in the environment were rare among isolates from human infection.
Conversely, disease-associated isolates either belonged to ubiquitous clones such
as C and PA14 or to clones that were uncommon in the environment. The P.
aeruginosa population consists of major clones that are just as versatile in
their habitat and geographic origin as the whole species and of minor clones with
preference for a peculiar niche.
PMID- 26419223
TI - Regrouping of pigs by body weight at weaning does not affect growth performance,
carcass quality or uniformity at slaughter of heavy weight pigs.
AB - We studied the influence of pen uniformity at weaning (7.5 +/- 0.6 kg vs. 7.5 +/-
1.2 kg body weight (BW +/- SD)) and sex on growth performance during the nursery
(7.5 to 27.3 kg BW) and the fattening (27.1 to 130.5 kg BW) phases and carcass
quality of barrows and castrated females (CF). During the nursery phase, pigs
from the more uniform pens had lower feed efficiency (P = 0.05) than pigs from
the less uniform pens. Also, barrows had higher average daily feed intake (ADFI)
(P < 0.05) and average daily gain (P < 0.001) and better feed efficiency (P <
0.001) than CF. During the fattening phase, initial pen uniformity did not affect
growth performance of the pigs but barrows tended (P = 0.08) to have higher ADFI
and worse feed efficiency than CF. Trimmed primal cut yield tended to be higher
for the more uniform pigs and better for barrows than for CF (P = 0.09). It is
concluded that regrouping of the pigs at weaning according to uniformity of BW
did not affect growth performance or carcass quality of the pigs at slaughter.
Castrated females might be used as an alternative to barrows for the production
of carcasses destined to the dry-cured industry.
PMID- 26419224
TI - Engineering excitonic dynamics and environmental stability of post-transition
metal chalcogenides by pyridine functionalization technique.
AB - Owing to their strong photon emission, low excitonic binding energies, and nearly
ideal band offset values for water splitting reactions, direct gap quasi-2D
gallium chalcogenides are potential candidates for applications in energy
harvesting, optoelectronics, and photonics. Unlike other 2D materials systems,
chemical functionalization of gallium chalcogenides is still at its seminal
stages. Here, we propose vapor phase pyridine intercalation technique to
manipulate optical properties of gallium chalcogenides. After functionalization,
the excitonic dynamics of quasi-2D GaSe change significantly as evidenced by an
increase in integrated PL intensity and emergence of a new emission feature that
is below the band edge. Based on our DFT calculations, we attribute these to
formation of bound exciton complexes at the trap sites introduced by chemical
reaction between pyridine and GaSe. On the contrary, pyridine functionalization
does not impact the optical properties of GaTe, instead treats GaTe surface to
prevent oxidization of tellurium atoms. Overall, results suggest novel ways to
control properties of gallium chalcogenides on demand and unleash their full
potential for a range of applications in photonics and optoelectronics.
PMID- 26419225
TI - Genetic risk for atrial fibrillation could motivate patient adherence to warfarin
therapy: a cost effectiveness analysis.
AB - BACKGROUND: Atrial fibrillation (AF) increases risk of stroke, and although this
stroke risk can be ameliorated by warfarin therapy, some patients decline to
adhere to warfarin therapy. A prospective clinical study could be conducted to
determine whether knowledge of genetic risk for AF could increase adherence to
warfarin therapy for patients who initially declined therapy. As a prelude to a
potential prospective clinical study, we investigated whether the use of genetic
information to increase adherence could be cost effective. METHODS: Markov model
assessed costs and utilities of two care strategies for AF patients who declined
warfarin therapy. In the usual care strategy patients received aspirin. In the
test strategy genetic risk for AF was assessed (genotype of the 4q25 locus) and
some patients with a positive genetic test (>=1 risk allele) were assumed to
adhere to warfarin therapy. The remaining patients received aspirin. The
incremental cost-effectiveness ratio (ICER) was the ratio of the costs
differential and the quality adjusted life-years (QALYs) differential for the two
strategies. RESULTS: We found that the 4q25 genetic testing strategy, compared
with the usual care strategy (aspirin therapy), would be cost-effective (ICER $
47,148) if 2.1 % or more of the test positive patients were to adhere to warfarin
therapy. The test strategy would become a cost saving strategy if 5.3 % or more
of the test positive patients were to adhere to warfarin therapy. If 20 % of test
positive patients were to adhere to warfarin therapy in a hypothetical cohort of
1000 patients, 7 stroke events would be prevented and 3 extra-cranial major
bleeding events would be caused over 5 years, resulting in a cost savings of ~
$250,000 and a net gain of 9 QALYs. DISCUSSION: A clinical study to assess the
impact of patient knowledge of genetic risk of AF on adherence to warfarin
therapy would be merited because even a modest increase in patient adherence
would make a genetic testing strategy cost-effective. CONCLUSION: Providing
patients who declined warfarin therapy with information about their genetic risk
of AF would be cost effective if this genetic risk information resulted in modest
increases in adherence.
PMID- 26419226
TI - Interventions for preventing, delaying the onset, or decreasing the burden of
frailty: an overview of systematic reviews.
AB - BACKGROUND: Many systematic reviews have evaluated the effectiveness of
interventions to prevent, delay, or decrease frailty symptoms, but no effort has
been made to identify, map, and synthesize the findings from reviews across the
full spectrum of interventions. Our objectives are to (1) synthesize findings
from all existing systematic reviews evaluating interventions for preventing,
delaying the onset, or decreasing the burden of frailty symptoms; (2) examine
different conceptualizations of frailty that have been used in the development
and implementation of interventions; and (3) inform policy by convening a
stakeholder dialogue with Canadian health-system leaders. METHODS/DESIGN: We will
conduct an overview of systematic reviews to identify and synthesize all of the
systematic reviews addressing interventions to preventing, delaying the onset, or
decreasing the burden of frailty symptoms. To identify relevant systematic
reviews, we will conduct database searches for published and grey literature as
well as contact key experts and search reference lists of included reviews. Two
reviewers will independently review all search results for inclusion and then
conceptually map, extract key findings (including the
conceptualization/definition of frailty used) and assess the methodological
quality of all included reviews. We will then synthesize the findings by
producing a 'gap map' (i.e. mapping reviews in a matrix according to the
interventions and outcomes assessed), and narratively synthesize the key messages
across reviews related to type of interventions. DISCUSSION: Following the
completion of the synthesis, we will use the findings to develop an evidence
brief that mobilizes the best available evidence about the problem related to
preventing, delaying the onset, or decreasing the burden of frailty symptoms in
older adults, policy and programmatic options to address the problem and
implementation considerations. The evidence brief will then be used as the input
into a stakeholder dialogue, which will engage 18-22 Canadian health-system
leaders (including policymakers, health providers, researchers, and other
stakeholders) in 'off-the-record' deliberations to inform future actions and
policymaking. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015022082.
PMID- 26419227
TI - Nanoparticle-rich diesel exhaust-induced liver damage via inhibited
transactivation of peroxisome proliferator-activated receptor alpha.
AB - Diesel exhaust emission contains a high amount of nano-sized particles and is
considered to be systemically distributed in the body. However, few studies about
the effects of nanoparticle rich-diesel exhaust (NR-DE) on liver have been
reported. The present investigation focuses on the effects of NR-DE on livers in
rats, especially concerning inflammation and lipid metabolism. Male F344 rats
were exposed to fresh air or low (24 +/- 7 ug/m3 ), medium (39 +/- 4 ug/m3 ) and
high (138 +/- 20 ug/m3 ) concentrations of NR-DE for 1, 2, or 3 months (5
hours/day, 5 days/week). Exposure to both medium and high concentrations of NR-DE
for one month increased plasma asparate aminotransferase and alanine
aminotransferase activities, while only high concentrations increased plasma
interleukin-6 and hepatic nuclear factor kappa B (NFkappaB), suggesting that
activation of hepatic inflammatory signaling took place. Although these exposures
elevated peroxisome proliferator-activated receptor (PPAR) alpha levels or its
binding activity to the response element, neither activated PPARalpha-target
genes such as beta-oxidative enzymes nor inhibited NFkappaB elevation. Thus, NR
DE may contain some materials that inhibit PPARalpha activation in relation to
lipid metabolism and inflammation. Taken together, NR-DE exposure at one month
may cause inflammation; however, this finding may not be observed after a longer
exposure period. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1985-1995,
2016.
PMID- 26419228
TI - Atypical bromethalin intoxication in a dog: pathologic features and
identification of an isomeric breakdown product.
AB - BACKGROUND: Definitive post mortem confirmation of intoxication by the neurotoxic
rodenticide bromethalin can be challenging. Brain lesions are not specific and
detection of bromethalin and its metabolites are unpredictable due to rapid
photodegradation and inconsistent behavior in tissues. CASE PRESENTATION: A 2
year-old dog presented with rapid onset of severe muscle tremors and death within
hours after a known ingestion of a reportedly low dosage of bromethalin and
subsequent decontamination using activated charcoal. Marked meningeal hemorrhages
and multifocal myelin sheath vacuolation were observed in the brain. A marked
reactive astrocytosis and neuronal hypoxia/necrosis were identified using
immunohistochemistry (IHC) for glial fibrillary acidic protein (GFAP) and for
neuron specific protein (NeuN). Bromethalin exposure and tissue absorption was
confirmed by identification of one of two isomeric 543.7 molecular weight (MW)
breakdown products in the patient's adipose and kidney samples using gas
chromatography (GC) combined with tandem quadrupole mass spectrometry (MS/MS).
CONCLUSIONS: The severity of clinical signs and subsequent death of this dog was
not expected with the low dosage of bromethalin reportedly ingested, and the use
of activated charcoal possibly precipitated a hypernatremic status. Meningeal
hemorrhages are atypical of bromethalin intoxication, and might have been caused
by hyperthermia, secondary to tremors or hypernatremia. Identification of one of
two isomeric breakdown products in the adipose tissue and kidney provides an
additional molecule to the toxicologic testing regime for bromethalin
intoxication.
PMID- 26419229
TI - Clostridium punense sp. nov., an obligate anaerobe isolated from healthy human
faeces.
AB - An obligately anaerobic, rod-shaped (0.5-1.0 * 2.0-10.0 MUm), Gram-stain-positive
bacterium, occurring mainly singly or in pairs, and designated BLPYG-8T, was
isolated from faeces of a healthy human volunteer aged 56 years. Cells were non
motile. Oval, terminal spores were formed that swell the cells. The strain was
affiliated with the genus Clostridium sensu stricto (Clostridium rRNA cluster I)
as revealed by 16S rRNA gene sequence analysis. Strain BLPYG-8T showed 97.3 to
97.4 % 16S rRNA gene sequence similarity with Clostridium sulfidigenes DSM
18982T, Clostridium subterminale DSM 6970T and Clostridium thiosulfatireducens
DSM 13105T. DNA-DNA hybridization and phenotypic analysis showed that the strain
was distinct from its closest relatives, C. sulfidigenes DSM 18982T, C.
subterminale DSM 6970T, C. thiosulfatireducens DSM 13105T with 54.2, 53.9 and
53.3 % DNA-DNA relatedness, respectively. Strain BLPYG-8T grew in PYG broth at
temperatures between 20 and 40 degrees C (optimum 37 degrees C). The strain
utilized a range of amino acids as well as carbohydrates as a source of carbon
and energy. Glucose fermentation resulted in the formation of volatile fatty
acids mainly acetic acid, n-butyric acid and organic acids such as succinic and
lactic acid. The DNA G+C content of strain BLPYG-8T was 44.1 mol%. The major
fatty acids (>10 %) were C14 : 0, iso-C15 : 0, C16 : 1omega7c and C16 : 0.
Phylogenetic analysis and specific phenotypic characteristics and/or DNA G+C
content differentiated the strain from its closest relatives. On the basis of
these data, strain BLPYG-8T represents a novel species of the genus Clostridium,
for which the name Clostridium punense sp. nov. is proposed. The type strain is
BLPYG-8T ( = DSM 28650T = CCUG 64195T = MCC 2737T).
PMID- 26419230
TI - Text message interventions for follow up of infants born to mothers positive for
Chagas disease in Tucuman, Argentina: a feasibility study.
AB - BACKGROUND: Diagnosis of congenital Chagas disease occurs at 9 months of age,
making effective treatment challenging due to loss to follow-up. Mobile health
(mHealth) has been utilized to improve communication and treatment adherence in
many chronic diseases, although no studies of mHealth in Trypanosoma cruzi
infected individuals have been conducted. Text message interventions, a subset of
mHealth, has shown to improve appointment attendance and is relatively simple to
set up, thus making it an ideal mechanism to facilitate communication with
individuals in low-resource settings. OBJECTIVE: The aim of this study is to
understand the acceptability, utilization, and barriers of an SMS-based
appointment reminder to confirm a post-partum home visit to women in Tucuman,
Argentina and whether these factors differ in urban and rural populations.
METHODS: Women that tested positive for Chagas disease were invited to receive
SMS reminders of their follow-up 4-week postpartum home visit. Demographic
information and SMS contact preferences were collected at hospital discharge, and
variables on mHealth utilization and barriers were recorded at follow-up.
RESULTS: 77 (70.6%) of women possessed a cell phone for personal use. All
eligible women owned phones compatible with SMS messages. The appointment
reminder SMS was widely accepted with 64/72 (88.9%) enrolled women receiving the
SMS message and 58/64 (90.6%) replying. Ninety-two percent of women stated that
the text message was a useful reminder for the follow-up home visit. Women living
in rural areas were less likely to own a cell phone for personal use and were
significantly less likely to have internet access on their phone than women
living in urban areas (RR 0.30, 95% CI 0.10-0.89). Furthermore, women from rural
areas faced barriers to mHealth uptake such as change of phone number and
response to messages from the hospital team at higher rates than women from urban
areas, although these differences were not statistically significant.
CONCLUSIONS: There is generally widespread acceptance and utilization of mHealth
among this group of women with access to cell phones. However, there are still
many barriers to overcome before mHealth interventions attain complete
penetration in a population, most notably the issue of cell phone for personal
use.
PMID- 26419231
TI - Neurodevelopmental outcome of extremely low birth weight infants at 24 months
corrected age: a comparison between Griffiths and Bayley Scales.
AB - BACKGROUND: The availability of accurate assessment tools for the early detection
of infants at risk for adverse neurodevelopmental outcomes is a major issue. The
purpose of this study is to compare the outcomes of the Bayley Scales (Bayley-II
vs Bayley-III) in a cohort of extremely low birth weight infants at 24 months
corrected age, to define which edition shows the highest agreement with the
Griffiths Mental Development Scales Revised. METHODS: We performed a single
centre cohort study. We prospectively enrolled infants with a birth weight of 401
1000 g and/or gestational age < 28 weeks. Exclusion criteria were the presence of
neurosensory disabilities and/or genetic abnormalities. Infants underwent
neurodevelopmental evaluation at 24 months corrected age using the Griffiths and
either the Bayley-II (birth years 2003-2006) or the Bayley-III (birth years 2007
2010). RESULTS: A total of 194 infants were enrolled. Concordance was excellent
between the Griffiths and the Bayley-III composite scores for both cognitive
language and motor abilities (weighted K = 0.80 and 0.81, respectively) but
poorer for the Bayley-II (weighted K = 0.63 and 0.50, respectively). The Youden's
Index revealed higher values for the Bayley-III than for the Bayley-II (75.9 vs
69.6%). Compared with the Griffiths, the Bayley-III found 3% fewer infants as
being severely impaired in cognitive-language abilities and 7.8% fewer infants as
being mildly impaired in motor skills while the Bayley-II showed, compared with
the Griffiths, higher rates of severely impaired children both for cognitive
language and motor abilities (14.1 and 15.3% more infants respectively).
DISCUSSION: Our study suggests that the Bayley-III, although having a higher
agreement with the Griffiths compared to the Bayley-II, slightly tends to
underestimate neurodevelopmental impairment compared with the Griffiths, whereas
the Bayley-II tends to overestimate it. CONCLUSIONS: On the basis of these
findings, we recommend the use of multiple measures to assess neurodevelopmental
outcomes of extremely low birth weight infants at 24 months.
PMID- 26419232
TI - Cryptic speciation in the Triatoma sordida subcomplex (Hemiptera, Reduviidae)
revealed by chromosomal markers.
AB - BACKGROUND: Chagas disease vectors (Hemiptera-Reduviidae) comprise more than 140
blood-sucking insect species of the Triatominae subfamily. The largest genus is
Triatoma, subdivided in several complexes and subcomplexes according to
morphology, ecology and genetic features. One of them is the sordida subcomplex,
involving four species: Triatoma sordida, T. guasayana, T. garciabesi and T.
patagonica. Given the great morphological similarity of these species, their
taxonomic identification, evolutionary relationships and population
differentiation have been controversial for many years and even today remain
under discussion. METHODS: We simultaneously analyzed two chromosomal markers, C
heterochromatin distribution and 45S ribosomal genes chromosomal position, of 139
specimens from several sordida subcomplex populations from Argentina, Bolivia,
Brazil and Paraguay, collected both in nature and from several established
insectaries. Our results were compared with COI sequences deposited in GenBank.
RESULTS: We recognized five chromosomal taxa with putative hybrids, which each
differ in at least one chromosome marker. Most of them present significant
differences in their mtDNA sequences. CONCLUSION: The chromosomal taxa here show
a significant chromosome differentiation involving changes in the C
heterochromatin content and in the ribosomal clusters position. This paper
identifies several erroneously classified populations by morphological methods,
delimits the geographical distribution of each taxon and proposes the existence
of a new cryptic species, widely distributed in Argentina. We also suggest that
sordida sibling species involve closely related as well as evolutionary distant
species. Taxonomic status of each chromosomal taxon is discussed considering
phenotypic and genetic results previously published.
PMID- 26419234
TI - Relational Aggression, Victimization and Self-Concept: Testing Pathways from
Middle Childhood to Adolescence.
AB - When studying adolescent development, it is important to consider two key areas
that are salient for teens, which are self-concept and peer relations. A
secondary analysis of the National Institute of Health and Human Development
Study of Early Child Care and Youth Development was conducted to examine the
prospective bidirectional associations between self-concept and peer relations.
To date, how social development broadly and peer relations in particular (e.g.,
relational aggression and victimization) affect self-concept domains is not fully
understood. Using a large sample (N = 1063; 532 girls; M = 11.14 years; SD = .59)
with multiple informants, the present study examined whether fifth grade
relational aggression and sixth grade relational victimization was associated
with adolescent self-concept in three key domains (i.e., academic, sports,
physical appearance). A significant direct effect emerged, such that relational
aggression in middle childhood was associated with decreases in academic self
concept and increases in sports self-concept in adolescence. Analyses also
revealed that having higher levels of domain specific self-concept led to
decreases in relational aggression across the transition to adolescence. The
findings highlight the importance of examining bidirectional prospective
associations between relational aggression, relational victimization, and domain
specific self-concept. Implications for future research and clinical intervention
are discussed.
PMID- 26419235
TI - Primary malignant lymphoma combined with clinically "silent" pheochromocytoma in
the same adrenal gland.
AB - An increased number of adrenal tumors are now diagnosed due to the increased
number of abdominal CT scans being performed. We present the first case of
malignant lymphoma combined with clinically "silent" pheochromocytoma in the same
adrenal gland. An abdominal CT scan demonstrates unilateral adrenal lesion which
suggests pheochromocytoma or adrenal carcinoma. Laboratory examinations revealed
a slight increase of 24-h urine vanillylmandelic acid and 24-h urinary
methanephrine excretion. Histological examination revealed two intermingled tumor
cell proliferations-diffuse B cell lymphoma and pheochromocytoma.Unexpected
coexistence of catecholamine-producing tumor with the other adrenal lesion can
lead to serious complications of diagnosis and treatment. The adequate
preparation for surgery can protect patient from threatening catecholamine
crisis.
PMID- 26419236
TI - PNPLA3 rs738409 Polymorphism Associated with Hepatic Steatosis and Advanced
Fibrosis in Patients with Chronic Hepatitis C Virus: A Meta-Analysis.
AB - BACKGROUND/AIMS: The recognition of a correlation between patatin-like
phospholipase domain containing-protein 3 (PNPLA3) rs738409 (C>G) and the
severity of liver steatosis or fibrosis in chronic hepatitis C (CHC) has not
reached a consensus. This meta-analysis sought to investigate with accuracy the
association between the PNPLA3 rs738409 (C>G) polymorphism and liver steatosis
and advanced fibrosis in CHC patients. METHODS: We performed a comprehensive
literature search from the PubMed, Embase, Web of Science, and Google Scholar
databases up to December 31, 2014. Crude odds ratios (ORs) with 95% confidence
intervals (CIs) were calculated. Statistical analyses were performed using Stata
12.0 software. RESULTS: The meta-analysis revealed the severity of liver fibrosis
was significantly higher in CHC patients with PNPLA3 rs738409 GG in Caucasians
(versus CC+CG OR, 2.29; 95% CI, 1.57 to 3.35; p<0.05) but not Asian populations.
In Caucasians, liver steatosis was also more severe in CHC patients with rs738409
GG (versus CC+CG; OR, 4.33; 95% CI, 2.59 to 7.22; p<0.05). The sensitivity
analysis indicated the results of this meta-analysis were stable and no
publication bias was detected. CONCLUSIONS: PNPLA3 rs738409 (C>G) was associated
with the risk of both advanced liver fibrosis and steatosis in patients with CHC,
especially among Caucasian populations.
PMID- 26419237
TI - Leukocyte telomere length and diabetes status, duration, and control: the 1999
2002 National Health and Nutrition Examination Survey.
AB - BACKGROUND: Studies investigating the association between telomere length and
diabetes have been inconsistent, and there are few data available investigating
the associations of telomere length with diabetes duration and control. We
evaluated the relationship of leukocyte telomere length with diabetes, and the
relationship of leukocyte telomere length with diabetes duration and poor glucose
control among people with diabetes. METHODS: We used data from the 1999-2002
National Health and Nutrition Examination Survey, a representative sample of the
US civilian non-institutionalized population. In 3921 participants, leukocyte
telomere length was measured and diabetes status was determined based on a
previous diagnosis, hemoglobin A1c >= 6.5 %, or fasting glucose >= 126 mg/dL.
RESULTS: The odds ratios (95 % confidence intervals) of diabetes associated with
the first, second, and third quartile of leukocyte telomere length, compared to
the highest quartile, was 2.09 (1.46-2.98), 1.74 (1.30-2.31), and 1.08 (0.76
1.54), respectively (p-trend < 0.01), in unadjusted models and 0.74 (0.48-1.14),
0.91 (0.61-1.34), and 0.87 (0.59-1.29), respectively (p-trend = 0.20), in
multivariable adjusted models. Among participants with diabetes, unadjusted and
adjusted leukocyte telomere length was not associated with diabetes duration or
glucose control based on an hemoglobin A1c < 7 or < 8 % (all p > 0.05).
CONCLUSIONS: In this study of the US general population, leukocyte telomere
length was not associated with diabetes status, diabetes duration, or diabetes
control.
PMID- 26419239
TI - Looking for a standardized approach in the surgical treatment of hyperhidrosis.
PMID- 26419240
TI - Circadian Insights into Motivated Behavior.
AB - For an organism to be successful in an evolutionary sense, it and its offspring
must survive. Such survival depends on satisfying a number of needs that are
driven by motivated behaviors, such as eating, sleeping, and mating. An
individual can usually only pursue one motivated behavior at a time. The
circadian system provides temporal structure to the organism's 24 hour day,
partitioning specific behaviors to particular times of the day. The circadian
system also allows anticipation of opportunities to engage in motivated behaviors
that occur at predictable times of the day. Such anticipation enhances fitness by
ensuring that the organism is physiologically ready to make use of a time-limited
resource as soon as it becomes available. This could include activation of the
sympathetic nervous system to transition from sleep to wake, or to engage in
mating, or to activate of the parasympathetic nervous system to facilitate
transitions to sleep, or to prepare the body to digest a meal. In addition to
enabling temporal partitioning of motivated behaviors, the circadian system may
also regulate the amplitude of the drive state motivating the behavior. For
example, the circadian clock modulates not only when it is time to eat, but also
how hungry we are. In this chapter we explore the physiology of our circadian
clock and its involvement in a number of motivated behaviors such as sleeping,
eating, exercise, sexual behavior, and maternal behavior. We also examine ways in
which dysfunction of circadian timing can contribute to disease states,
particularly in psychiatric conditions that include adherent motivational states.
PMID- 26419238
TI - Novel MASP1 mutations are associated with an expanded phenotype in 3MC1 syndrome.
AB - BACKGROUND: 3MC1 syndrome is a rare autosomal recessive disorder characterized by
intellectual disability, short stature and distinct craniofacial, umbilical, and
sacral anomalies. Five mutations in MASP1, encoding lectin complement pathway
enzymes MASP-1 and MASP-3, have thus far been reported to cause 3MC1 syndrome.
Only one previously reported mutation affects both MASP-1 and MASP-3, while the
other mutations affect only MASP-3. METHODS: We evaluated six unrelated
individuals with 3MC1 syndrome and performed Sanger sequencing for all coding
exons of MASP1. We also measured complement lectin and alternative pathway
activities in an affected individual's serum. RESULTS: We found two novel splice
site mutations, c.1012-2A > G in one and c.891 + 1G > T in two probands, and
three novel missense mutations, c.1451G > A (p.G484E), c.1657G > A (p.D553N), and
c.1987G > T (p.D663Y). Missense mutations affect only MASP-3, while splice site
mutations affect both MASP-1 and MASP-3. In a proband who is homozygous for c.891
+ 1G > T, we detected a total lack of lectin complement pathway activity and a
2.5-fold lower alternative pathway activity. The phenotype observed in patients
whose both MASP-1 and MASP-3 are affected and in those whose only MASP-3 is
affected does not appear to be different. We observed structural brain
abnormalities, neonatal tooth, a vascular anomaly and a solid lesion in liver as
novel phenotypic features of 3MC1 syndrome. CONCLUSION: Novel mutations and
additional phenotypic features expand the genotypic and phenotypic spectrum of
3MC1 syndrome. Although patients with MASP-1 dysfunction in addition to disrupted
MASP-3 have an altered complement system, their disease phenotype is not
different from those having only MASP-3 dysfunction.
PMID- 26419241
TI - Distress from Motivational Dis-integration: When Fundamental Motives Are Too Weak
or Too Strong.
AB - Past research has shown that satisfying different kinds of fundamental motives
contributes to well-being. More recently, advances in motivational theory have
shown that z is also tied to the integration of different motives. In other
words, well-being depends not only on maximizing effectiveness in satisfying
specific motives, but also on ensuring that motives work together such that no
individual motive is too weak or too strong. In this chapter, we review existing
research to show that specific forms of psychological distress can be linked to
specific types of motivational imbalance or dis-integration. Such disintegration
can arise from either excessive weakness of a specific motive or the excessive
strength and/or dominance of a specific motive, thereby inhibiting other motives.
Possible neural correlates and avenues of intervention are discussed.
PMID- 26419242
TI - Integrating Qualitative and Quantitative Tools for the Detection and
Identification of Lectins in Major Human Diseases.
AB - Lectins are the (glyco)proteins that recognize and bind to specific sugar
moieties without altering their structure. Galectins are mammalian lectins
characterized by the presence of conserved 134 amino acids carbohydrate
recognition domain and specificity for beta-galactosides. The involvement of
lectins in diverse biological spectrum, especially some deadly human diseases
like cancer, neurological disorders and cardiovascular disorders has proclaimed
them as one of the important components of glycobiology, thereby seeking the
methods of their detection and identification heavily desirable. In the present
manuscript, we have provided a comprehensive outline of various methods of
detection and identification of lectins employed till date, with their needs and
usage varying according to the level of infrastructure of laboratories and around
the world. In addition, a vision for some quick, highly sensitive and advanced
methods for lectin detection and identification for diagnostic and therapeutic of
various diseases is also provided.
PMID- 26419243
TI - Post-concussion syndrome (PCS) in a youth population: defining the diagnostic
value and cost-utility of brain imaging.
AB - PURPOSE: Approximately 90% of concussions are transient, with symptoms resolving
within 10-14 days. However, a minority of patients remain symptomatic several
months post-injury, a condition known as post-concussion syndrome (PCS). The
treatment of these patients can be challenging. The goal of our study was to
assess the utility and cost-effectiveness of neurologic imaging two or more weeks
post-injury in a cohort of youth with PCS. METHODS: We conducted a retrospective
study of 52 pediatric patients with persistent post-concussion symptoms after 3
months. We collected demographics and neuroimaging results obtained greater than
2 weeks post-concussion. Neuroimaging ordered in the first 2 weeks post
concussion was excluded, except to determine the rate of re-imaging. Descriptive
statistics and corresponding cost data were collected. RESULTS: Of 52 patients
with PCS, 23/52 (44%) had neuroimaging at least 2 weeks after the initial injury,
for a total of 32 diagnostic studies. In summary, 1/19 MRIs (5.3%), 1/8 CTs
(13%), and 0/5 x-rays (0%) yielded significant positive findings, none of which
altered clinical management. Chronic phase neuroimaging estimated costs from
these 52 pediatric patients totaled $129,025. We estimate the cost to identify a
single positive finding was $21,000 for head CT and $104,500 for brain MRI.
CONCLUSIONS: In this cohort of pediatric PCS patients, brain imaging in the
chronic phase (defined as more than 2 weeks after concussion) was pursued in
almost half the study sample, had low diagnostic yield, and had poor cost
effectiveness. Based on these results, outpatient management of pediatric
patients with long-term post-concussive symptoms should rarely include repeat
neuroimaging beyond the acute phase.
PMID- 26419244
TI - Microbial availability of mercury: effective detection and organic ligand effect
using a whole-cell bioluminescent bioreporter.
AB - A luxCDABE-based genetically engineered bacterial bioreporter (Escherichia coli
ARL1) was used to detect bioavailable ionic mercury (Hg(II)) and investigate the
effects of humic acids and ethylenediaminetetraacetic acid (EDTA) on the
bioavailability of mercury in E. c oli. Results showed that the E. c oli ARL1
bioreporter was sensitive to mercury, with a detection limit of Hg(II) of 0.5
ug/L and a linear dose/response relationship up to 2000 ug Hg(II)/L. Humic acids
and EDTA decreased the Hg(II)-induced bioluminescent response of strain ARL1,
suggesting that the two organic ligands reduced the bioavailability of Hg(II) via
complexation with Hg(II). Compared with traditional chemical methods, the use of
E. c oli ARL1 is a cost-effective, rapid, and reliable approach for measuring
aqueous mercury at very low concentrations and thus has potential for
applications in field in situ monitoring.
PMID- 26419245
TI - Biological toxicity of cellulose nanocrystals (CNCs) against the luxCDABE-based
bioluminescent bioreporter Escherichia coli 652T7.
AB - The aim of this study was to evaluate the biological toxicity of cellulose
nanocrystals (CNCs) using the constitutively bioluminescent luxCDABE-based
bioreporter Escherichia coli 652T7. The effects of CNCs on E. c oli 652T7
biotoxicity were investigated at different CNC concentrations, reaction times,
and IC50 values. CNC toxicity was also compared with and without ultrasonic
dispersion to establish dispersibility effects. The results demonstrated that
CNCs were not significantly toxic at concentrations at or below 250 mg/L. At
concentrations higher than 300 mg/L, toxicity increased linearly as CNC
concentrations increased up to 2000 mg/L. IC50 calculations demonstrated an
increase in cytotoxicity as CNC exposure times increased, and elevated
dispersibility of the CNCs were shown to increase cytotoxicity effects. These
results suggest that CNCs can impact microbial populations if elevated
concentration thresholds are met.
PMID- 26419246
TI - The relationship between perioperative administration of inhaled corticosteroid
and postoperative respiratory complications after pulmonary resection for non
small-cell lung cancer in patients with chronic obstructive pulmonary disease.
AB - OBJECTIVES: Inhaled corticosteroid (ICS) treatment has been shown to increase the
risk of respiratory complications in patients with stable chronic obstructive
pulmonary disease (COPD). However, the effects of perioperative ICS treatment on
postoperative respiratory complications after lung cancer surgery have not been
elucidated. The aim of this study was to investigate whether perioperative ICS
treatment would increase the risk of postoperative respiratory complications
after lung cancer surgery in patients with COPD. METHODS: We retrospectively
analyzed 174 consecutive COPD patients with non-small-cell lung cancer (NSCLC)
who underwent lobectomy or segmentectomy between January 2007 and December 2014.
Subjects were grouped based on whether or not they were administered
perioperative ICS treatment. Postoperative cardiopulmonary complications were
compared between the groups. RESULTS: There were no statistically significant
differences in the incidence of postoperative respiratory complications (P =
0.573) between the perioperative ICS treatment group (n = 16) and the control
group (n = 158). Perioperative ICS treatment was not significantly associated
with postoperative respiratory complications in the univariate or multivariate
analysis (odds ratio [OR] = 0.553, 95% confidence interval [CI] = 0.069-4.452, P
= 0.578; OR = 0.635, 95% CI = 0.065-6.158, P = 0.695, respectively). Kaplan-Meier
analysis showed that there were no statistically significant differences in the
postoperative respiratory complications-free durations between the groups (P =
0.566), even after propensity score matching (P = 0.551). CONCLUSION: There was
no relationship between perioperative ICS administration and the incidences of
postoperative respiratory complications after surgical resection for NSCLC in
COPD patients.
PMID- 26419247
TI - A novel biodegradable external mesh stent improved long-term patency of vein
grafts by inhibiting intimal-medial hyperplasia in an experimental canine model.
AB - OBJECTIVES: Increased hemodynamic stress on vein grafts used in the arterial
system is associated with vein graft disease. We determined whether a novel
biodegradable external mesh stent could inhibit medial-intimal hyperplasia by
suppressing hemodynamic stress on vein grafts and improve long-term patency.
METHODS: Twenty-four beagles underwent bilateral femoral interposition grafting
using reversed femoral veins. Vein grafts were externally supported by a novel
poly L-lactide-epsilon-caprolactone copolymer (P(LA/CL)) biodegradable mesh stent
or a nonabsorbable mesh stent. Vein grafts with no reinforcement were used as
controls. The grafts were harvested 6 and 12 months after implantation for
morphometric and immunohistochemical assessment. RESULTS: The endoluminal
circumferential vein graft length was smaller in the P(LA/CL) and nonabsorbable
groups (17.2 +/- 2.9 and 19.0 +/- 0.3 mm, respectively), than that in the control
group (25.0 +/- 2.6 mm, P < 0.01) at 12 months. The mean intimal-medial thickness
was thinner in P(LA/CL) and nonabsorbable stent groups (0.18 +/- 0.05 and 0.16 +/
0.05 mm, respectively), than that in the control group (0.30 +/- 0.08 mm, P <
0.01). Differences in the intimal-medial thickness among the groups were
associated with the magnitude of cellular proliferating activity. The graft
patency ratio (100 %) was higher in the P(LA/CL) group than that in the
nonabsorbable and control groups (72.2 and 63.6%, respectively, P < 0.05).
CONCLUSIONS: The biodegradable P(LA/CL) external mesh stent improved vein graft
patency for 12 months and prevented vein graft dilatation and intimal hyperplasia
associated with suppressed neointimal layer cellular proliferating activity.
PMID- 26419248
TI - Avoidable perioperative mortality at the University Teaching Hospital, Lusaka,
Zambia: a retrospective cohort study.
AB - PURPOSE: Perioperative mortality has fallen in both high- and low-income
countries over the last 50 years. An evaluation of avoidable perioperative
mortality can provide valuable lessons to improve care; however, there is
relatively little recent data from the Least Developed Countries in the world. We
aimed to compare recent avoidable perioperative mortality in Lusaka, Zambia, with
historical data from 1987. METHODS: We conducted a retrospective cohort study by
identifying perioperative deaths within days of surgery and comparing the
operating room and mortuary registers for the 2012 calendar year. Multiple
independent raters from anesthesiology and surgery/obstetrics gynecology reviewed
case notes, when available, to identify avoidable causes of death. RESULTS: Of
the 18,010 surgical patients in 2012, 114 were identified as having died
perioperatively within six days of surgery. Fifty-nine files were available for
further analysis (52% of identified perioperative deaths). Eighteen (30%) of
these cases were assessed as avoidable, 19 cases (32%) probably avoidable, 14
cases (24%) unavoidable, and eight cases (14%) unclear. Thirty-one (53%) cases
had surgical factors contributing to death, 19 (32%) cases had anesthesia
factors, and 18 (30%) cases had systems factors. Most of the avoidable deaths
were attributed to multiple factors. Key factors leading to the avoidable deaths
were delays in surgery, lack of the availability of blood, and poor postoperative
care. CONCLUSIONS: Most deaths were avoidable, suggesting that patient outcomes
in low-resource settings can be improved within current resources. The
multifactorial nature of avoidability implies that an interprofessional approach
is required to improve the quality of care.
PMID- 26419249
TI - Cadmium (Cd) Localization in Tissues of Cotton (Gossypium hirsutum L.), and Its
Phytoremediation Potential for Cd-Contaminated Soils.
AB - Phytoremediation using economically valuable, large biomass, non-edible plants is
a promising method for metal-contaminated soils. This study investigated cotton's
tolerance for Cd and remediation potential through analyzing Cd bioaccumulation
and localization in plant organs under different soil Cd levels. Results showed
cotton presents good tolerance when soil Cd concentration <=20.26 mg kg(-1).
Cotton had good Cd accumulation ability under low soil Cd levels (<1.26 mg kg(
1)), with a TF value (the ratio of Cd concentration in stem to root) above 1.
Energy dispersive X-ray microanalysis indicated cotton leaf transpiration played
a key role in extracting soil Cd, while roots and stems were the main
compartments of Cd storage. Cd complexation to other organic constituents in root
and stem cell sap could be a primary detoxifying strategy. Therefore, cotton is a
potential candidate for phytoremediation of Cd-contaminated soils.
PMID- 26419250
TI - Cognitive behavioural therapy shows promise in heart failure patients with
depression.
PMID- 26419251
TI - Health of adolescents is targeted in new UN strategy.
PMID- 26419252
TI - Delayed hospital admission until active labour may help prevent unnecessary
caesarean delivery.
PMID- 26419254
TI - Diagnostic performance and radiation dose of lower extremity CT angiography using
a 128-slice dual source CT at 80 kVp and high pitch.
AB - BACKGROUND: Multi-detector computed tomography (MDCT) angiography is now used for
the diagnosing patients with peripheral arterial disease. The dose of radiation
is related to variable factors, such as tube current, tube voltage, and helical
pitch. PURPOSE: To assess the diagnostic performance and radiation dose of lower
extremity CT angiography (CTA) using a 128-slice dual source CT at 80 kVp and
high pitch in patients with critical limb ischemia (CLI). MATERIAL AND METHODS:
Twenty-eight patients (mean, 64.1 years; range, 39-80 years) with CLI were
enrolled in this retrospective study and underwent CTA using a 128-slice dual
source CT at 80 kVp and high pitch and subsequent intra-arterial digital
subtraction angiography (DSA), which was used as a reference standard for
assessing diagnostic performance. RESULTS: For arterial segments with significant
disease (>50% stenosis), overall sensitivity, specificity, and accuracy of lower
extremity CTA were 94.8% (95% CI, 91.7-98.0%), 91.5% (95% CI, 87.7-95.2%), and
93.1% (95% CI, 90.6-95.6%), respectively, and its positive and negative
predictive values were 91.0% (95% CI, 87.1-95.0%), and 95.1% (95% CI, 92.1
98.1%), respectively. Mean radiation dose delivered to lower extremities was
266.6 mGy.cm. CONCLUSION: Lower extremity CTA using a 128-slice dual source CT at
80 kVp and high pitch was found to have good diagnostic performance for the
assessment of patients with CLI using an extremely low radiation dose.
PMID- 26419255
TI - Inter- and intraobserver agreement in detection of testicular microlithiasis with
ultrasonography.
AB - BACKGROUND: Ultrasonography of the testis is a well-established diagnostic tool
in detection of testicular microlithiasis (TML). Operator-dependent diagnostic
variation related to skill, knowledge, and operator consistency are factors that
influence detection of TML. PURPOSE: To determine inter- and intraobserver
agreement for detection of TML using ultrasonography for a group of physicians
with no or limited experience compared to a group of experience senior
radiologists. MATERIAL AND METHODS: Between May and September 2014 a total of six
observers evaluated 34 patients scrotal ultrasonography recorded from September
to December 2013. The observers were blinded to patient history and previous
ultrasonography. Three of the observers had no or limited experience with
detection of TML, and three of the observers had more than 15 years of
experience. Each observer reviewed all the scrotal ultrasonography recordings
twice with a time interval of 3 months. RESULTS: The inter-observer agreement
showed substantial agreement and up to almost perfect agreement (kappa = 0.86).
Both the experienced and less experienced observers had a higher agreement in
detecting and grading TML in their second reading. CONCLUSION: The
ultrasonography grading system of TML in this study showed to be reproducible,
with an inter- and intraobserver agreement ranging between substantial agreement
and up to almost perfect agreement with many years of experience not necessarily
being essential.
PMID- 26419256
TI - Heat-Treatment-Responsive Proteins in Different Developmental Stages of Tomato
Pollen Detected by Targeted Mass Accuracy Precursor Alignment (tMAPA).
AB - Recently, we have developed a quantitative shotgun proteomics strategy called
mass accuracy precursor alignment (MAPA). The MAPA algorithm uses high mass
accuracy to bin mass-to-charge (m/z) ratios of precursor ions from LC-MS
analyses, determines their intensities, and extracts a quantitative sample versus
m/z ratio data alignment matrix from a multitude of samples. Here, we introduce a
novel feature of this algorithm that allows the extraction and alignment of
proteotypic peptide precursor ions or any other target peptide from complex
shotgun proteomics data for accurate quantification of unique proteins. This
strategy circumvents the problem of confusing the quantification of proteins due
to indistinguishable protein isoforms by a typical shotgun proteomics approach.
We applied this strategy to a comparison of control and heat-treated tomato
pollen grains at two developmental stages, post-meiotic and mature. Pollen is a
temperature-sensitive tissue involved in the reproductive cycle of plants and
plays a major role in fruit setting and yield. By LC-MS-based shotgun proteomics,
we identified more than 2000 proteins in total for all different tissues. By
applying the targeted MAPA data-processing strategy, 51 unique proteins were
identified as heat-treatment-responsive protein candidates. The potential
function of the identified candidates in a specific developmental stage is
discussed.
PMID- 26419258
TI - Concentration Effects on the Entropy of Electrochemical Lithium Deposition:
Implications for Li(+) Solvation.
AB - The solvation behavior of Li(+) in ethylene carbonate and dimethylcarbonate upon
dilution has been investigated by electrochemical microcalorimetry. We measured
the heat effects at a Li electrode upon electrochemical Li deposition and
dissolution from Li(+) solutions of varying concentration. The exchanged heat is
correlated to the entropy of lithium deposition and therefore reveals information
about the solvation of Li(+). Lithium deposition from electrolytes with lower
concentrations showed less entropy gain than deposition from electrolytes with
higher concentrations. This can be fully explained by the entropy of dilution of
the Li(+) ions. From our data we further concluded that the inner coordination
shell of the Li(+) ions does not significantly change between 0.01 and 1 M Li(+)
concentration. The results also suggest that contact ion pairs, which are
probably present in the electrolyte, show a similar solvation behavior as regular
lithium ions.
PMID- 26419257
TI - CSAR Benchmark Exercise 2013: Evaluation of Results from a Combined Computational
Protein Design, Docking, and Scoring/Ranking Challenge.
AB - Community Structure-Activity Resource (CSAR) conducted a benchmark exercise to
evaluate the current computational methods for protein design, ligand docking,
and scoring/ranking. The exercise consisted of three phases. The first phase
required the participants to identify and rank order which designed sequences
were able to bind the small molecule digoxigenin. The second phase challenged the
community to select a near-native pose of digoxigenin from a set of decoy poses
for two of the designed proteins. The third phase investigated the ability of
current methods to rank/score the binding affinity of 10 related steroids to one
of the designed proteins (pKd = 4.1 to 6.7). We found that 11 of 13 groups were
able to correctly select the sequence that bound digoxigenin, with most groups
providing the correct three-dimensional structure for the backbone of the protein
as well as all atoms of the active-site residues. Eleven of the 14 groups were
able to select the appropriate pose from a set of plausible decoy poses. The
ability to predict absolute binding affinities is still a difficult task, as 8 of
14 groups were able to correlate scores to affinity (Pearson-r > 0.7) of the
designed protein for congeneric steroids and only 5 of 14 groups were able to
correlate the ranks of the 10 related ligands (Spearman-rho > 0.7).
PMID- 26419259
TI - Mesenchymal stem cells-conditioned medium protects PC12 cells against 2,5
hexanedione-induced apoptosis via inhibiting mitochondria-dependent caspase 3
pathway.
AB - Studies suggested that the conditioned medium of mesenchymal stem cells (MSC-CM)
inhibited the increased apoptosis in various cells. However, there are no reports
underlying the protection of MSC-CM against 2,5-hexanedione (HD)-induced
apoptosis in neural cells. In the present study, the viability was observed in
PC12 cells that received HD alone or with MSC-CM by 3-(4,5-dimethylthiazol-2-yl)
2,5-diphenyltetrazolium bromide assay. Apoptosis was estimated by Hoechst 33342
staining and flow cytometry. Mitochondrial transmembrane potential was examined
by rhodamine 123. Moreover, we investigated the expression of Bax and Bcl-2,
cytochrome c translocation, and caspase 3 activity by real-time polymerase chain
reaction, Western blot, and immunochemistry. Nerve growth factor (NGF) was
examined in MSCs and MSC-CM. Our results showed that MSC-CM promoted cell
survival and reduced apoptosis in HD-exposed PC12 cells. Moreover, MSC-CM
significantly reversed disturbance of Bax and Bcl-2, ameliorated disruption of
mitochondrial transmembrane potential, and reduced release of cytochrome c and
activity of caspase 3 in HD-exposed PC12 cells. In the meantime, NGF was detected
in MSCs and MSC-CM. These findings demonstrate that MSC-CM protects against HD
induced apoptosis in PC12 cells via inhibiting mitochondrial pathway. Our results
indicate that NGF in MSC-CM may be involved in the protection of MSC-CM against
HD-induced apoptosis. Our study clarifies the protection of MSC-CM on HD
neurotoxicity and its underlying mechanism.
PMID- 26419260
TI - Genotoxic and oxidative stress potential of nanosized and bulk zinc oxide
particles in Drosophila melanogaster.
AB - Zinc oxide nanoparticles (ZnONP) are manufactured on a large scale and can be
found in a variety of consumer products, such as sunscreens, lotions, paints and
food additives. Few studies have been carried out on its genotoxic potential and
related mechanisms in whole organisms. In the present study, the in vivo
genotoxic activity of ZnONP and its bulk form was assayed using the wing-spot
test and comet assay in Drosophila melanogaster Additionally, a lipid
peroxidation analysis using the thiobarbituric acid assay was also performed.
Results obtained with the wing-spot test showed a lack of genotoxic activity of
both ZnO forms. However, when both particle sizes were tested in the comet assay
using larvae haemocytes, a significant increase in DNA damage was observed for
ZnONP treatments but only at the higher dose applied. In addition, the lipid
peroxidation assay showed significant malondialdehyde (MDA) induction for both
ZnO forms, but the induction of MDA for ZnONP was higher for the ZnO bulk,
suggesting that the observed DNA strand breaks could be induced by mediated
oxidative stress. The overall data suggest that the potential genotoxicity of
ZnONP in Drosophila can be considered weak according to the lack of mutagenic and
recombinogenic effects and the induction of primary DNA damage only at high toxic
doses of ZnONP. This study is the first assessing the genotoxic and oxidative
stress potential of nano and bulk ZnO particles in Drosophila.
PMID- 26419261
TI - Mechanisms of chromium hexavalent-induced apoptosis in rat testes.
AB - Hexavalent chromium (CrVI)-containing compounds, present in industrial settings
and in the environment, are known as carcinogens and mutagens. The present study
is designed to test the hypothesis that oxidative stress mediates CrVI-induced
apoptosis in testis. Male Wistar rats received an intraperitoneal injection of
potassium dichromate at doses of 1 and 2 mg kg-1. Superoxide anion production was
assessed by the determination of the reduction of cytochrome c and
iodonitrotetrazolium, lipid peroxidation (LPO), metallothioneins (MTs), and
catalase (CAT) activity. Apoptosis was evaluated by DNA fragmentation detected by
agarose gel electrophoresis. Germinal cells apoptosis was detected by toluidine
blue staining. The expression of Bax and Bcl-2 proteins (Pts) was also
investigated. After 15 days of treatment, an increase of LPO and MT levels
occurred, while CAT activity was decreased. Testicular tissues of treated rats
showed pronounced degradation of the DNA into oligonucleotides as seen in the
typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in
germinal cells of Cr-exposed rats. Bax Pt expression was induced in spermatogonia
and spermatocytes cells of CrVI-treated rats. In contrast, Bcl-2 Pt was
occasionally observed in germ cells of CrVI-exposed rats. These results clearly
suggest that CrVI subacute treatment causes oxidative stress in rat testis
leading to apoptosis.
PMID- 26419262
TI - Identifying present challenges to reliable future transdermal drug delivery
products.
AB - Transdermal systems have become an accepted means of drug delivery, offering
clinical benefits over other dosage forms. Although transdermal delivery has been
very successful as a controlled release technology platform, there are a number
of challenges that prevent this delivery route from achieving its fullest
commercial potential. Additionally, beginning in 1997, transdermal drug delivery
companies aligned with life science industries to deliver large molecules,
peptides and proteins through the skin, which is difficult due to the skin
barrier properties. A number of methods and technologies have been conceived to
overcome the skin barrier. Among these are mechanical, chemical and thermal
permeation enhancement techniques. These methods are briefly discussed as well as
future directions for transdermal therapies.
PMID- 26419264
TI - Analyzing the potential for incorrect haplotype calls with different
pharmacogenomic assays in different populations: a simulation based on 1000
Genomes data.
AB - AIM: Many currently available pharmacogenomic assays and algorithms interrogate a
set of 'tag' polymorphisms for inferring haplotypes. We wanted to test the
accuracy of such haplotype inferences across different populations. MATERIALS &
METHODS: We simulated haplotype inferences made by existing pharmacogenomic
assays for seven important pharmacogenes based on full genome data of 2504
persons in the 1000 Genomes dataset. RESULTS: A sizable fraction of samples did
not match any of the haplotypes in the star allele nomenclature systems. We found
no clear population bias in the accuracy of results of simulated assays.
CONCLUSION: Haplotype nomenclatures and inference algorithms need to be improved
to adequately capture pharmacogenomic diversity in human populations.
PMID- 26419271
TI - Psychological, endocrine, and neural correlates of attentional bias in
subclinical depression.
AB - BACKGROUND: Our knowledge with respect to psychological, endocrine, and neural
correlates of attentional bias in individuals with high vulnerability to
developing depression - the subclinically depressed, still remains limited.
DESIGN: The study used a 2 * 2 mixed design. METHODS: Attentional bias toward
happy and sad faces in healthy (N = 26) and subclinically depressed individuals
(N = 22) was assessed via a neuroimaging dot-probe attention task. Participants
also completed trait and state psychological measures and provided saliva samples
for cortisol analysis. RESULTS: The subclinical group showed attentional bias
toward happy faces; past use of problem-focused coping strategies when dealing
with a personally relevant stressor as well as state levels of anxiety, together,
contributed to this bias. In the control group, the happy attentional bias was
positively correlated with activity in the right caudate. In the subclinical
group, the bias was negatively associated with the left fusiform gyrus and
positively with the left inferior parietal lobule and bilateral putamen. We
observed group differences in association between cortisol levels during the task
and neural activity during happy attentional bias processing within the key
regions involved in attention. CONCLUSIONS: The attentional bias toward happy
faces may reflect an active coping attempt by the subclinical participants.
PMID- 26419272
TI - Sections 3 and 37 of the Mental Health Act 1983 - a comparison.
PMID- 26419263
TI - Targeting EPO and EPO receptor pathways in anemia and dysregulated
erythropoiesis.
AB - INTRODUCTION: Recombinant human erythropoietin (rhEPO) is a first-line
therapeutic for the anemia of chronic kidney disease, cancer chemotherapy, AIDS
(Zidovudine therapy), and lower-risk myelodysplastic syndrome. However, rhEPO
frequently elevates hypertension, is costly, and may affect cancer progression.
Potentially high merit therefore exists for defining new targets for anti-anemia
agents within erythropoietin (EPO) and EPO receptor (EPOR) regulatory circuits.
AREAS COVERED: EPO production by renal interstitial fibroblasts is subject to
modulation by several regulators of hypoxia-inducible factor 2a (HIF2a) including
Iron Response Protein-1, prolyl hydroxylases, and HIF2a acetylases, each of which
holds potential as anti-anemia drug targets. The cell surface receptor for EPO
(EPOR) preassembles as a homodimer, together with Janus Kinase 2 (JAK2), and
therefore it remains attractive to develop novel agents that trigger EPOR complex
activation (activating antibodies, mimetics, small-molecule agonists).
Additionally, certain downstream transducers of EPOR/JAK2 signaling may be
druggable, including Erythroferrone (a hepcidin regulator), a cytoprotective
Spi2a serpin, and select EPOR-associated protein tyrosine phosphatases. EXPERT
OPINION: While rhEPO (and biosimilars) are presently important mainstay
erythropoiesis-stimulating agents (ESAs), impetus exists for studies of novel
ESAs that fortify HIF2a's effects, act as EPOR agonists, and/or bolster select
downstream EPOR pathways to erythroid cell formation. Such agents could lessen
rhEPO dosing, side effects, and/or costs.
PMID- 26419274
TI - Highly luminescent gold nanoparticles: effect of ruthenium distance for
nanoprobes with enhanced lifetimes.
AB - The photophysical properties of gold nanoparticles, AuNPs, with sizes of 13, 50
and 100 nm in diameter, coated with surface-active ruthenium complexes have been
studied to investigate the effect of the distance of the ruthenium luminescent
centre from the gold surface. Luminescence lifetimes of the three ruthenium
probes, RuS1, RuS6 and RuS12, with different length spacer units between the
surface active groups and the ruthenium centre were taken. The metal complexes
were attached to AuNP13, AuNP50 and AuNP100 via thiol groups using a method of
precoating the nanoparticles with a fluorinated surfactant. The luminescence
lifetime of the longer spacer unit complex, RuS12, was enhanced by 70% upon
attachment to the AuNP when compared to the increase of the short and medium
linker unit complexes, RuS1 (20%) and (RuS6 40%) respectively. The effect of the
surfactant in the lifetime increase of the ruthenium coated AuNPs was shown to be
larger for the medium spacer probe, RuS6. There was no effect of the change of
the size of the AuNPs from 13 to 50 or 100 nm.
PMID- 26419273
TI - Clinical negligence in hospitals in France and England.
AB - This article arose from the back-to-back presentations by Michael Kelly and
Patrice Metayer to the Anglo-French Medical Society in 2013 on the French and
English legal systems handling a case of alleged clinical negligence as it
proceeds from complaint to settlement or judgment in the two jurisdictions. Both
systems have a hospital-based first stage with various avenues being available
for amicable resolution, the French version being more regulated and prescribed
than the English one. In both jurisdictions fewer than 5% cases go down the
criminal route. Before the court is involved, in England there is an elaborate
lawyer-controlled phase involving negotiations between the two sides and their
experts which is expensive but often leads to pre-trial settlement for
significant sums of money. Medical experts are central to all of this. In England
they are largely unregulated and entirely advisory in an open market, in France
they are both regulated and supervised by judges, being placed on official lists.
These experts take a major inquisitorial role in a Debate between the two sides,
combining the functions of Single Joint Expert (SJE), arbiter and mentor. If
agreement is not reached, a second Debate before a different Expert is arranged.
In both countries fewer than 5% cases reach a court for a hearing before a judge.
In England a trial is an elaborate lengthy, expensive adversarial contest where
all of the issues are rehearsed in full with factual and expert evidence, whereas
in France in a contested case the judge reviews the reports of the two Debates
with the lawyers who were involved (and not the experts, factual witnesses or
parties).
PMID- 26419275
TI - Peroxidase-like oxidative activity of a manganese-coordinated histidyl
bolaamphiphile self-assembly.
AB - A peroxidase-like catalyst was constructed through the self-assembly of histidyl
bolaamphiphiles coordinated to Mn(2+) ions. The prepared catalyst exhibited
oxidation activity for the organic substrate o-phenylenediamine (OPD) in the
presence of hydrogen peroxide (H2O2). The histidyl bolaamphiphiles of bis(N-alpha
amido-histidine)-1,7-heptane dicarboxylates self-assembled to make spherical
structures in an aqueous solution. Subsequent association of Mn(2+) ions with the
histidyl imidazoles in the self-assembly produced catalytic active sites. The
optimal Mn(2+) ion concentration was determined and coordination of the Mn(2+)
ion with multiple histidine imidazoles was investigated using spectroscopy
analysis. The activation energy of the produced catalysts was 55.0 kJ mol(-1),
which was comparable to other peroxidase-mimetic catalysts. A detailed kinetics
study revealed that the prepared catalyst followed a ping-pong mechanism and that
the turnover reaction was promoted by increasing the substrate concentration.
Finally, application of the prepared catalyst for glucose detection was
demonstrated through cascade enzyme catalysis. This study demonstrated a facile
way to prepare an enzyme-mimetic catalyst through the self-assembly of an
amphiphilic molecule containing amino acid segments.
PMID- 26419277
TI - A comparison of exposure to risk factors for giardiasis in non-travellers,
domestic travellers and international travellers in a Canadian community, 2006
2012.
AB - The purpose of this study is to determine how demographic and exposure factors
related to giardiasis vary between travel and endemic cases. Exposure and
demographic data were gathered by public health inspectors from giardiasis cases
reported from the Region of Waterloo from 2006 to 2012. Logistic regression
models were fit to assess differences in exposure to risk factors for giardiasis
between international travel-related cases and Canadian acquired cases while
controlling for age and sex. Multinomial regression models were also fit to
assess the differences in risk profiles between international and domestic travel
related cases and endemic cases. Travel-related cases (both international and
domestic) were more likely to go camping or kayaking, and consume untreated water
compared to endemic cases. Domestic travel-related cases were more likely to
visit a petting zoo or farm compared to endemic cases, and were more likely to
swim in freshwater compared to endemic cases and international travel-related
cases. International travellers were more likely to swim in an ocean compared to
both domestic travel-related and endemic cases. These findings demonstrate that
travel-related and endemic cases have different risk exposure profiles which
should be considered for appropriately targeting health promotion campaigns.
PMID- 26419278
TI - A rare variant (c.863G>T) in exon 7 of SMN1 disrupts mRNA splicing and is
responsible for spinal muscular atrophy.
AB - Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular
disorder caused by deletion or mutation of SMN1 (survival motor neuron 1). SMN
exon 7 splicing is regulated by a number of exonic and intronic regulatory
sequences and the trans-factors that bind them. Variants located in or near these
regulated regions should be evaluated to determine their effect on splicing. We
identified the rare variant c.863G>T (r.835_*3del, p.Gly279Glufs*5) in exon 7 of
SMN1 in three patients affected with type I or type II SMA. Most of the SMN1
transcripts exhibited complete loss of exon 7 in vivo. The ex vivo splicing assay
demonstrated that the variant disrupts inclusion of exon 7 (~85%) in the SMN1
mRNA; replacement with various bases yielded a variety of splicing effects in
SMN1 and SMN2 pre-mRNA. The c.863G>T (r.835_*3del, p.Gly279Glufs*5) variant is
located in a region that includes binding sites for multiple splicing factors
including Tra2beta1. Thus, the variant disrupts Tra2beta1 binding, but does not
affect binding of hnRNP A1. These findings demonstrate how rare variants
influence pre-mRNA splicing of SMN and reveal the functional influence of
c.863G>T (r.835_*3del, p.Gly279Glufs*5) variant in patients with SMA.
PMID- 26419279
TI - D117N in Cypher/ZASP may not be a causative mutation for dilated cardiomyopathy
and ventricular arrhythmias.
AB - Dilated cardiomyopathy (DCM) and malignant ventricular arrhythmias are important
causes of congestive heart failure, heart transplantation, and sudden cardiac
death in young patients. Cypher/ZASP is a cytoskeletal protein localized in the
sarcomeric Z-line that has a pivotal role in maintaining adult cardiac structure
and function. The putative mutation p.(D117N) in Cypher/ZASP has been suggested
to cause systolic dysfunction, dilated left ventricle with hypertrabeculated
myocardium, and intraventricular conduction disturbance, based on two reported
sporadic cases. In two unrelated Bedouin families, one with pediatric DCM and the
other with DCM and ventricular arrhythmias at young adulthood searching for the
causative mutation by exome sequencing we identified the p.(D117N) variant in
Cypher/ZASP. However, p.(D117N) did not segregate as the causative mutation in
these families, i.e. it was not present in some patients and was found in several
individuals who had no clinical manifestations. Furthermore, the carrier
frequency in the Bedouin population of origin is estimated to be 5.2%, which is
much higher than the incidence of idiopathic DCM in this population. Thus, our
data support the notion that the p.(D117N) variant in Cypher/ZASP is not a
causative mutation in the families tested by us. The results also indicates that
at least in some cases, the p.(D117N) in Cypher/ZASP is not a causative mutation
and the role of D117N in Cypher/ZASP in cardiac pathologies should be further
clarified and re-evaluated.
PMID- 26419280
TI - Corrigendum: Enhanced role of eddies in the Arctic marine biological pump.
PMID- 26419281
TI - Hypothalamic overexpression of mutant huntingtin causes dysregulation of brown
adipose tissue.
AB - Expression of mutant huntingtin (htt) protein has been shown to cause metabolic
imbalance in animal models of Huntington disease (HD). The pathways involved are
not fully understood but dysfunction of both the hypothalamus and brown adipose
tissue (BAT) has been implicated. Here we show that targeted expression of mutant
HTT in the hypothalamus leads to loss of the A13 dopaminergic cell group located
in the zona incerta and reduced mRNA expression of neuropeptide Y1 receptor in
the hypothalamus. Furthermore, this is accompanied by downregulation of
uncoupling protein 1 expression and PPARgamma coactivator-1 alpha in BAT and a
rapid body weight gain. Taken together, our data might provide a mechanistic link
between expression of mutant HTT, reduced activity of a hypothalamic dopaminergic
pathway and dysfunction of BAT and in part explain the development of an obese
phenotype in HD mouse models.
PMID- 26419282
TI - Mode-resolved frequency comb interferometry for high-accuracy long distance
measurement.
AB - Optical frequency combs have developed into powerful tools for distance
metrology. In this paper we demonstrate absolute long distance measurement using
a single femtosecond frequency comb laser as a multi-wavelength source. By
applying a high-resolution spectrometer based on a virtually imaged phased array,
the frequency comb modes are resolved spectrally to the level of an individual
mode. Having the frequency comb stabilized against an atomic clock, thousands of
accurately known wavelengths are available for interferometry. From the
spectrally resolved output of a Michelson interferometer a distance is derived.
The presented measurement method combines spectral interferometry, white light
interferometry and multi-wavelength interferometry in a single scheme. Comparison
with a fringe counting laser interferometer shows an agreement within <10(-8) for
a distance of 50 m.
PMID- 26419283
TI - Antigen exposure in the late light period induces severe symptoms of food allergy
in an OVA-allergic mouse model.
AB - The mammalian circadian clock controls many physiological processes that include
immune responses and allergic reactions. Several studies have investigated the
circadian regulation of intestinal permeability and tight junctions known to be
affected by cytokines. However, the contribution of circadian clock to food
allergy symptoms remains unclear. Therefore, we investigated the role of the
circadian clock in determining the severity of food allergies. We prepared an
ovalbumin food allergy mouse model, and orally administered ovalbumin either late
in the light or late in the dark period under light-dark cycle. The light period
group showed higher allergic diarrhea and weight loss than the dark period group.
The production of type 2 cytokines, IL-13 and IL-5, from the mesenteric lymph
nodes and ovalbumin absorption was higher in the light period group than in the
dark period group. Compared to the dark period group, the mRNA expression levels
of the tight junction proteins were lower in the light period group. We have
demonstrated that increased production of type 2 cytokines and intestinal
permeability in the light period induced severe food allergy symptoms. Our
results suggest that the time of food antigen intake might affect the
determination of the severity of food allergy symptoms.
PMID- 26419284
TI - Pancreatic Cancer: Promises and Failures of Target Therapies.
AB - Currently, few efficient therapies are available to battle pancreatic cancer.
Mechanisms underlying this cancer are not well known and researchers are trying
to identify new therapeutic targets. Here, we present a review of new treatments
and their results in recent years.
PMID- 26419285
TI - Understanding Particle Formation: Solubility of Free Fatty Acids as Polysorbate
20 Degradation Byproducts in Therapeutic Monoclonal Antibody Formulations.
AB - The purpose of this work was to determine the aqueous solubilities at 2-8
degrees C of the major free fatty acids (FFAs) formed by polysorbate 20 (PS20)
degradation and identify possible ways to predict, delay, or mitigate subsequent
particle formation in monoclonal antibody (mAb) formulations. The FFA solubility
limits at 2-8 degrees C were determined by titrating known amounts of FFA in
monoclonal antibody formulations and identifying the FFA concentration leading to
visible and subvisible particle formation. The solubility limits of lauric,
myristic, and palmitic acids at 2-8 degrees C were 17 +/- 1 MUg/mL, 3 +/- 1
MUg/mL, and 1.5 +/- 0.5 MUg/mL in a formulation containing 0.04% (w/v) PS20 at pH
5.4 and >22 MUg/mL, 3 +/- 1 MUg/mL, and 0.75 +/- 0.25 MUg/mL in a formulation
containing 0.02% (w/v) PS20 at pH 6.0. For the first time, a 3D correlation
between FFA solubility, PS20 concentration, and pH has been reported providing a
rational approach for the formulator to balance these with regard to potential
particle formation. The results suggest that the lower solubilities of the longer
chain FFAs, generated from degradation of the stearate, palmitate, and myristate
fraction of PS20, is the primary cause of seeding and subsequent FFA
precipitation rather than the most abundant lauric acid.
PMID- 26419286
TI - Transgenerational Adaptation to Pollution Changes Energy Allocation in
Populations of Nematodes.
AB - Assessing the evolutionary responses of long-term exposed populations requires
multigeneration ecotoxicity tests. However, the analysis of the data from these
tests is not straightforward. Mechanistic models allow the in-depth analysis of
the variation of physiological traits over many generations, by quantifying the
trend of the physiological and toxicological parameters of the model. In the
present study, a bioenergetic mechanistic model has been used to assess the
evolution of two populations of the nematode Caenorhabditis elegans in control
conditions or exposed to uranium. This evolutionary pressure resulted in a brood
size reduction of 60%. We showed an adaptation of individuals of both populations
to experimental conditions (increase of maximal length, decrease of growth rate,
decrease of brood size, and decrease of the elimination rate). In addition,
differential evolution was also highlighted between the two populations once the
maternal effects had been diminished after several generations. Thus, individuals
that were greater in maximal length, but with apparently a greater sensitivity to
uranium were selected in the uranium population. In this study, we showed that
this bioenergetics mechanistic modeling approach provided a precise, certain, and
powerful analysis of the life strategy of C. elegans populations exposed to heavy
metals resulting in an evolutionary pressure across successive generations.
PMID- 26419287
TI - Atomic layer deposition on 2D transition metal chalcogenides: layer dependent
reactivity and seeding with organic ad-layers.
AB - This commmunication presents a study of atomic layer deposition of Al2O3 on
transition metal dichalcogenide (TMD) two-dimensional films which is crucial for
use of these promising materials for electronic applications. Deposition of Al2O3
on pristine chemical vapour deposited MoS2 and WS2 crystals is demonstrated. This
deposition is dependent on the number of TMD layers as there is no deposition on
pristine monolayers. In addition, we show that it is possible to reliably seed
the deposition, even on the monolayer, using non-covalent functionalisation with
perylene derivatives as anchor unit.
PMID- 26419288
TI - Interactions of Histone Acetyltransferase p300 with the Nuclear Proteins Histone
and HMGB1, As Revealed by Single Molecule Atomic Force Spectroscopy.
AB - One of the important properties of the transcriptional coactivator p300 is
histone acetyltransferase (HAT) activity that enables p300 to influence chromatin
action via histone modulation. p300 can exert its HAT action upon the other
nuclear proteins too--one notable example being the transcription-factor-like
protein HMGB1, which functions also as a cytokine, and whose accumulation in the
cytoplasm, as a response to tissue damage, is triggered by its acetylation.
Hitherto, no information on the structure and stability of the complexes between
full-length p300 (p300FL) (300 kDa) and the histone/HMGB1 proteins are available,
probably due to the presence of unstructured regions within p300FL that makes it
difficult to be crystallized. Herein, we have adopted the high-resolution atomic
force microscopy (AFM) approach, which allows molecularly resolved three
dimensional contour mapping of a protein molecule of any size and structure. From
the off-rate and activation barrier values, obtained using single molecule
dynamic force spectroscopy, the biochemical proposition of preferential binding
of p300FL to histone H3, compared to the octameric histone, can be validated.
Importantly, from the energy landscape of the dissociation events, a model for
the p300-histone and the p300-HMGB1 dynamic complexes that HAT forms, can be
proposed. The lower unbinding forces of the complexes observed in acetylating
conditions, compared to those observed in non-acetylating conditions, indicate
that upon acetylation, p300 tends to weakly associate, probably as an outcome of
charge alterations on the histone/HMGB1 surface and/or acetylation-induced
conformational changes. To our knowledge, for the first time, a single molecule
level treatment of the interactions of HAT, where the full-length protein is
considered, is being reported.
PMID- 26419289
TI - Increased frequency of co-existing JAK2 exon-12 or MPL exon-10 mutations in
patients with low JAK2(V617F) allelic burden.
AB - The frequency of co-existing JAK2(V617F)/MPL and JAK2(V617F)/JAK2 exon-12
mutations has not been previously investigated in MPNs. Poor survival was
reported in primary myelofibrosis with low JAK2(V617F) allelic burden. However,
mutational status of JAK2 exon-12 or MPL were not reported in these patients.
This study developed a cost-effective multiplex high resolution melt assay that
screens for mutations in JAK2 gene exons-12 and -14 ((V617F)) and MPL gene exon
10. Co-existing mutations with JAK2(V617F) were detected in 2.9% (6/208; two JAK2
exon-12 and four MPL exon-10) patient specimens with known JAK2(V617F) (allelic
burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with <
12% JAK2(V617F) allelic burden. Current WHO guidelines do not recommend further
testing once JAK2(V617F) mutation is detected in MPNs. The findings, however,
indicate that quantification of JAK2(V617F) allele burden may be clinically
relevant in MPNs and in those with low allelic burden additional testing for JAK2
exon-12 and MPL exon-10 mutation should be pursued.
PMID- 26419290
TI - Microneedles: bench to bedside.
AB - Microneedles are tiny micron-sized structures, made of a variety of materials,
used to minimally disrupt the outermost layer of the skin for enhancing the
delivery of therapeutic molecules across the skin. They are sufficiently long
enough just to breach the stratum corneum barrier but too short to reach the
nerve endings that perceive pain. Treating the skin using microneedles results in
the creation of aqueous microchannels that promote delivery of molecules
practically of any size. Small molecules, proteins, vaccines and diagnostic
agents can be delivered using microneedles. This technology that has started with
microstructures made of metal and silicon has now undergone significant advances
in the last decade and currently there are microneedle products in the market.
PMID- 26419292
TI - The electronic structures and photophysical properties of platinum complexes with
C^N^N ligands: the influence of the carborane substituent.
AB - Carboranes have attracted increasing interest in the scientific community due to
their remarkable structures and strong electron-withdrawing abilities. In this
article, four platinum complexes [(C^N^N)PtC[triple bond, length as m
dash]CPh](1), [(C^N^N)PtC[triple bond, length as m-dash]C-TPA](2),
[(C^N^N)PtC[triple bond, length as m-dash]C-TAB](3), [(C^N^N)PtC[triple bond,
length as m-dash]C-CB](4) (where TPA = triphenylamine, TAB = triarylboryl, CB = o
carborane) have been calculated via density functional theory (DFT) and time
dependent density functional theory (TDDFT) methods to mainly explore the
influence of carborane substituents on electronic structures, photophysical
properties and radiative decay processes. The calculated results reveal that 2
with electron-donating triphenylamine has a low radiative decay rate constant and
a red-shifted emission band, but 3 and 4 containing electron-withdrawing
triarylboryl and o-carborane exhibit the opposite properties, especially 4 is
supposed to have the highest phosphorescence quantum yield with the smallest
nonradiative decay rate constant. These findings successfully illustrated the
structure-property relationship and the designed complex 4 with carborane can
serve as a highly efficient phosphorescent material in the future.
PMID- 26419291
TI - Quantifying the value of biomarkers for predicting mortality.
AB - PURPOSE: In light of widespread interest in the prognostic value of biomarkers,
we apply three discrimination measures to evaluate the incremental value of
biomarkers--beyond self-reported measures--for predicting all-cause mortality. We
assess whether all three measures--area under the receiver-operating
characteristic curve, continuous net reclassification improvement, and integrated
discrimination improvement--lead to the same conclusions. METHODS: We use
longitudinal data from a nationally representative sample of older Taiwanese (n =
639, aged 54 or older in 2000, examined in 2000 and 2006, with mortality follow
up through 2011). We estimate age-specific mortality using a Gompertz hazard
model. RESULTS: The broad conclusions are consistent across the three
discrimination measures and support the inclusion of biomarkers, particularly
inflammatory markers, in household surveys. Although the rank ordering of
individual biomarkers varies across discrimination measures, the following is
true for all three: interleukin-6 is the strongest predictor, the other three
inflammatory markers make the top 10, and homocysteine ranks second or third.
CONCLUSIONS: The consistency of most of our findings across metrics should
provide comfort to researchers using discrimination measures to evaluate the
prognostic value of biomarkers. However, because the degree of consistency varies
with the level of detail inherent in the research question, we recommend that
researchers confirm results with multiple discrimination measures.
PMID- 26419293
TI - Effect of cariprazine across the symptoms of mania in bipolar I disorder:
Analyses of pooled data from phase II/III trials.
AB - Bipolar I disorder is a chronic disorder characterized by episodic recurrences of
mania, depression, and mixed affective states interspersed with periods of full
or partial remission; subsyndromal residual symptoms between episodes are common
and disabling. Cariprazine, an atypical antipsychotic, is a potent dopamine D3
and D2 receptor partial agonist with preferential binding to D3 receptors. Post
hoc analyses of pooled data from 3 positive trials were conducted to evaluate the
effect of cariprazine 3-12 mg/d on the symptoms of mania in inpatients (18-65
years) with bipolar I disorder and a current manic episode. Analyses were based
on the pooled intent-to-treat (ITT) population (placebo=429; cariprazine=608).
Mean change from baseline to the end of treatment on individual Young Mania
Rating Scale (YMRS) items was analysed using a mixed-effects model for repeated
measures (MMRM); categorical symptom severity shifts were analysed using logistic
regression. Statistically significant improvement in mean change was seen for
cariprazine versus placebo on all 11 YMRS items (p<0.0001); significantly more
cariprazine- versus placebo-treated patients had mild/no symptoms at the end of
treatment on 11 YMRS items (p<0.0001) and concurrently on the 4 YMRS core
symptoms (irritability, speech, content, and disruptive-aggressive behaviour)
(p<0.0001). Significantly more cariprazine- versus placebo-treated patients
shifted from a Moderate/Worse or Marked/Worse Symptoms categories to Mild/No
Symptoms on all 11 (p<0.0001) and 9 of 11 YMRS items (p<0.05), respectively.
Results suggest that cariprazine treatment improved mania across YMRS symptoms; a
significant percentage of cariprazine- versus placebo-treated patients had
mild/no symptoms at the end of treatment.
PMID- 26419295
TI - Is Smoking a Predictor for Acute Mountain Sickness? Findings From a Meta
Analysis.
AB - AIM: Studies of the potential association between cigarette smoking and acute
mountain sickness (AMS) have reached contradictory conclusions. Our aim was to
perform a meta-analysis of studies across a range of populations to ascertain
better the true relationship between cigarette smoking and AMS. MATERIALS AND
METHODS: We used the PRISMA protocol to identify and screen eligible studies of
smoking and AMS. Databases including Pubmed and Google Scholar were searched,
using the terms "smoking" and "acute mountain sickness." We conducted a meta
analysis of the selected studies in order to evaluate causal inference, evaluate
potential biases, and investigate possible sources of heterogeneity across
studies. RESULTS: We identified 3907 publications, of which 29 were eligible for
inclusion by reporting smoking status and AMS. Of these, eight publications were
excluded because they were duplicative or were lacking quantitative data. The 21
studies analyzed included 16 566 subjects. These fell into two groups:
occupational/military (n = 8) or volunteers/trekkers/mixed (n = 13). Study
heterogeneity was high (X (2) = 55.5, P < .001). Smoking was not statistically
associated with increased risk of AMS: pooled OR = 0.88 (95% CI = 0.74-1.05).
Stratification yielded similar risk estimates among the occupational/military
studies versus all others and studies at relatively higher and lower altitudes.
CONCLUSIONS: Overall, smoking was not statistically significantly associated with
AMS: there is no consistent effect of cigarette smoking acting as either a
protective factor against or a risk factor for AMS. IMPLICATIONS: This is the
first quantitative assessment of published studies on smoking and AMS, which
shows smoking to be neither a risk, nor protective. Studies specifically focusing
on smoking as a risk factor, should guide further research on this issue.
Although all smokers should be strongly advised to quit, studies on risk factors
for AMS focusing on other exposures could shed light on the full range of risks
for AMS.
PMID- 26419294
TI - Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF
in the brain regions of a learned helplessness rat model and the antidepressant
effects of a TrkB agonist and antagonist.
AB - Role of brain-derived neurotrophic factor (BDNF)-TrkB signaling in a learned
helplessness (LH) model of depression was investigated. LH rats showed a
reduction of BDNF in the medial prefrontal cortex (mPFC), CA3, and dentate gyrus
(DG) of the hippocampus, whereas LH rats showed an increase in BDNF in the
nucleus accumbens (NAc). Furthermore, levels of proBDNF, a BDNF precursor, were
higher in the mPFC, but lower in the NAc, of LH rats. A single bilateral infusion
of a TrkB agonist 7,8-DHF, but not a TrkB antagonist ANA-12, into the infralimbic
(IL) of mPFC, DG, and CA3, but not the prelimbic (PrL) of mPFC, exerted
antidepressant effects in LH rats. In contrast, a single bilateral infusion of
ANA-12, but not 7,8-DHF, into the core and shell of NAc exerted antidepressant
like effects in LH rats, with more potent effects observed for the NAc core than
for NAc shell. Interestingly, a single administration of 7,8-DHF (10mg/kg, i.p.)
significantly improved a decreased phosphorylation of TrkB in the mPFC, CA3, and
DG of LH rats. Additionally, ANA-12 (0.5mg/kg, i.p.) significantly improved an
increased phosphorylation of TrkB in the NAc of LH rats. In conclusion, these
results suggest that LH causes depression-like behavior by altering BDNF in the
brain regions, and that proBDNF-BDNF processing and transport may be altered in
the mPFC-NAc circuit of LH rats. Therefore, TrkB agonists might exert
antidepressant effects by stimulating TrkB in the IL, CA3, and DG, while TrkB
antagonists might exert antidepressant effects by blocking TrkB in the NAc.
PMID- 26419297
TI - [G. Bleu and D. Subtil in reply to the correspondence by D. Riethmuller on their
article entitled: Assessment of vacuum-assisted delivery in a frank breech
presentation. Gynecol Obstet Fertil 2015;43:123-7].
PMID- 26419296
TI - Feasibility of a self-rehabilitation program for the upper limb for stroke
patients in Benin.
AB - INTRODUCTION: Stroke is a major cause of disability and represents a very high
cost in developing countries. Self-rehabilitation programs represent a new and
original treatment for stroke patients, likely to reduce upper limb impairments
and improve activity and participation. The goal of this study is to evaluate the
feasibility of a self-rehabilitation protocol in Benin. METHODS: Twelve chronic
stroke patients carried out the upper limb self-rehabilitation program (3
hours/day, 5 days/week for 2 weeks). The performance of these patients was
evaluated before and after the self-rehabilitation program, by measuring the
number of exercises that patients were able to achieve during a three-hour
session, and by assessing their gross manual dexterity. RESULTS: Twelve patients
were effectively able to complete the entire program. The number of unimanual
exercises and self-mobilizations performed during a three-hour session as well as
the score of the Box and Block test were improved by the self-rehabilitation
program (P<0.05). DISCUSSION AND CONCLUSION: Self-rehabilitation programs are
feasible and inexpensive as they do not involve a therapist. It is then a
promising approach in stroke rehabilitation, particularly in developing
countries, where rehabilitation costs are usually supported by patients.
PMID- 26419298
TI - Glucocorticoid pharmacogenetics in pediatric idiopathic nephrotic syndrome.
AB - Idiopathic nephrotic syndrome represents the most common type of primary
glomerular disease in children: glucocorticoids (GCs) are the first-line therapy,
even if considerable interindividual differences in their efficacy and side
effects have been reported. Immunosuppressive and anti-inflammatory effects of
these drugs are mainly due to the GC-mediated transcription regulation of pro-
and anti-inflammatory genes. This mechanism of action is the result of a complex
multistep pathway that involves the glucocorticoid receptor and several other
proteins, encoded by polymorphic genes. Aim of this review is to highlight the
current knowledge on genetic variants that could affect GC response, particularly
focusing on children with idiopathic nephrotic syndrome.
PMID- 26419306
TI - ACR BI-RADS Use in Low-Income Countries: An Analysis of Diagnostic Breast
Ultrasound Practice in Uganda.
PMID- 26419305
TI - In vitro-in vivo correlation for complex non-oral drug products: Where do we
stand?
AB - In vitro-in vivo correlation (IVIVC) is a predictive mathematical model
describing the relationship between an in vitro property and a relevant in vivo
response of drug products. Since the U.S. Food and Drug Administration (FDA)
published a regulatory guidance on the development, evaluation, and applications
of IVIVC for extended release (ER) oral dosage forms in 1997, IVIVC has been one
of the most important issues in the field of pharmaceutics. However, even with
the aid of the FDA IVIVC Guidance, only very limited Abbreviated New Drug
Application (ANDA) submission for ER oral drug products included adequate IVIVC
data to enable the completion of bioequivalence (BE) review within first review
cycle. Establishing an IVIVC for non-oral dosage forms has remained extremely
challenging due to their complex nature and the lack of in vitro release methods
that are capable of mimicking in vivo drug release conditions. This review
presents a general overview of recent advances in the development of IVIVC for
complex non-oral dosage forms (such as parenteral polymeric
microspheres/implants, and transdermal formulations), and briefly summarizes the
knowledge gained over the past two decades. Lastly this review discusses possible
directions for future development of IVIVC for complex non-oral dosage forms.
PMID- 26419307
TI - From Gatekeeper to Steward: The Evolving Concept of Radiologist Accountability
for Imaging Utilization.
PMID- 26419308
TI - Thyroid Ultrasound Reporting Lexicon: White Paper of the ACR Thyroid Imaging,
Reporting and Data System (TIRADS) Committee.
AB - Ultrasound is the most commonly used imaging technique for the evaluation of
thyroid nodules. Sonographic findings are often not specific, and definitive
diagnosis is usually made through fine-needle aspiration biopsy or even surgery.
In reviewing the literature, terms used to describe nodules are often poorly
defined and inconsistently applied. Several authors have recently described a
standardized risk stratification system called the Thyroid Imaging, Reporting and
Data System (TIRADS), modeled on the BI-RADS system for breast imaging. However,
most of these TIRADS classifications have come from individual institutions, and
none has been widely adopted in the United States. Under the auspices of the ACR,
a committee was organized to develop TIRADS. The eventual goal is to provide
practitioners with evidence-based recommendations for the management of thyroid
nodules on the basis of a set of well-defined sonographic features or terms that
can be applied to every lesion. Terms were chosen on the basis of demonstration
of consistency with regard to performance in the diagnosis of thyroid cancer or,
conversely, classifying a nodule as benign and avoiding follow-up. The initial
portion of this project was aimed at standardizing the diagnostic approach to
thyroid nodules with regard to terminology through the development of a lexicon.
This white paper describes the consensus process and the resultant lexicon.
PMID- 26419309
TI - Health Resources and Services Agency Issues New National Practitioner Data Bank
Guidebook.
PMID- 26419310
TI - Integrating a Community Hospital-Based Radiology Department With an Academic
Medical Center.
PMID- 26419311
TI - Proton Beam Therapy Basics.
PMID- 26419312
TI - Intestinal immune function, antioxidant status and tight junction proteins mRNA
expression in young grass carp (Ctenopharyngodon idella) fed riboflavin deficient
diet.
AB - This study investigated the effects of riboflavin on intestinal immunity, tight
junctions and antioxidant status of young grass carp (Ctenopharyngodon idella).
Fish were fed diets containing graded levels of riboflavin (0.63-10.04 mg/kg
diet) for 8 weeks. The study indicated that riboflavin deficiency decreased
lysozyme, acid phosphatase, copper/zinc superoxide dismutase, glutathione
reductase and glutathione peroxidase activities, and contents of complement
component 3 and reduced glutathione in the intestine of fish (P < 0.05).
Meanwhile, riboflavin deficiency increased reactive oxygen species,
malondialdehyde and protein carbonyl contents and catalase activity (P < 0.05) in
the intestine of fish. Furthermore, real-time polymerase chain reaction analysis
was used to investigate mRNA expression patterns and found that the mRNA levels
of interleukin 10 and transforming growth factor beta1, Occludin, zonula
occludens 1, Claudin-b and Claudin-c, inhibitor protein kappaBalpha, target of
rapamycin, ribosomal S6 protein kinase 1 and NF-E2-related factor 2, copper/zinc
superoxide dismutase, glutathione peroxidase and glutathione reductase were
decreased (P < 0.05) in the intestine of fish fed riboflavin-deficient diet.
Conversely, the mRNA levels of tumor necrosis factor alpha, interleukin 1beta,
interleukin 8, nuclear factor kappa B p65, Ikappa B kinase beta, Ikappa B kinase
gamma, Kelch-like-ECH-associated protein 1b, p38 mitogen-activated protein
kinase, myosin light chain kinase and Claudin-12 were increased (P < 0.05) in the
intestine of fish fed riboflavin-deficient diet. In conclusion, riboflavin
deficiency decreased immunity and structural integrity of fish intestine. The
optimum riboflavin level for intestinal acid phosphatase activity of young grass
carp was estimated to be 6.65 mg/kg diet.
PMID- 26419313
TI - Structure and gelation properties of casein micelles doped with curcumin under
acidic conditions.
AB - In this study, the ability of micellar casein (MC) to interact with curcumin
during acidification and to produce acid gel was investigated. Steady-state
fluorescence spectroscopy of curcumin variation and fluorescence quenching of
caseins upon binding with curcumin molecules were evidenced. Increasing the
temperature from 20 to 35 degrees C enhanced MC-curcumin interactions as
reflected by the increase in the binding constant from 0.6 +/- 0.3 * 10(4) to 6.6
+/- 0.6 * 10(4) M(-1). From changes in entropy, enthalpy and Gibbs free energy,
hydrophobic interactions were proposed as major binding forces. Static
fluorescence MC quenching was demonstrated for the MC-curcumin complex during
acidification. From pH 7.4 to pH 5.0, the binding site numbers varied in the
range from 1.25 +/- 0.05 to 1.49 +/- 0.05 and the binding constant kb varied from
3.9 +/- 0.4 * 10(4) to 7.5 +/- 0.7 * 10(4) M(-1). Small angle X-ray scattering
profiles demonstrated that the MC internal structure was unchanged upon curcumin
binding. The zeta-potential value of curcumin-doped MC indicated that curcumin
did not modify the global charge of MC particles. Acid gelation studied by
oscillation rheology and static multiple light scattering at 20 and 35 degrees C
led to a similar behavior for native and curcumin-doped MC suspensions. For the
first time, it was demonstrated that the colloidal and functional properties of
MC were unchanged when doped with curcumin during acidification.
PMID- 26419315
TI - Exploration of graphene oxide as an intelligent platform for cancer vaccines.
AB - We explored an intelligent vaccine system via facile approaches using both
experimental and theoretical techniques based on the two-dimensional graphene
oxide (GO). Without extra addition of bio/chemical stimulators, the microsized GO
imparted various immune activation tactics to improve the antigen immunogenicity.
A high antigen adsorption was acquired, and the mechanism was revealed to be a
combination of electrostatic, hydrophobic, and pi-pi stacking interactions. The
"folding GO" acted as a cytokine self-producer and antigen reservoir and showed a
particular autophagy, which efficiently promoted the activation of antigen
presenting cells (APCs) and subsequent antigen cross-presentation. Such a "One
but All" modality thus induced a high level of anti-tumor responses in a
programmable way and resulted in efficient tumor regression in vivo. This work
may shed light on the potential use of a new dimensional nano-platform in the
development of high-performance cancer vaccines.
PMID- 26419318
TI - Nanoporous Materials Can Tune the Critical Point of a Pure Substance.
AB - Molecular simulations and NMR relaxometry experiments demonstrate that pure
benzene or xylene confined in isoreticular metal-organic frameworks (IRMOFs)
exhibit true vapor-liquid phase equilibria where the effective critical point may
be reduced by tuning the structure of the MOF. Our results are consistent with
vapor and liquid phases extending over many MOF unit cells. These results are
counterintuitive since the MOF pore diameters are approximately the same length
scale as the adsorbate molecules. As applications of these materials in
catalysis, separations, and gas storage rely on the ability to tune the
properties of adsorbed molecules, we anticipate that the ability to
systematically control the critical point, thereby preparing spatially
inhomogeneous local adsorbate densities, could add a new design tool for MOF
applications.
PMID- 26419319
TI - Abnormal behaviours during pramipexole treatment for Cotard's syndrome: a case
report.
AB - Cotard's syndrome is a relatively rare condition that involves a delusion of
negation in which an individual believes he or she has lost his or her soul, is
dead, or is without functional body systems. This syndrome is observed in various
neuropsychiatric disorders but most commonly in mood disorders. Pramipexole has
often been used in the adjunctive treatment of both bipolar and unipolar
depression, and it is known to cause rare but serious adverse effects such as
compulsive behaviours in the treatment of Parkinson's disease. Here we report a
case of Cotard's syndrome in treatment-resistant major depression associated with
abnormal behaviours that might be caused by pramipexole. In the present case, the
patient's abnormal behaviours gradually disappeared about 2 months after the
discontinuation of pramipexole. The hypoperfusion in the bilateral parieto
occipital lobe found on single-photon emission computed tomography suggests the
presence of Lewy body disease pathology. Nonetheless, the patient's abnormal
behaviours disappeared after the discontinuation of pramipexole, indicating that
they are mainly attributable to pramipexole treatment. However, the possible
existence of Lewy body pathology could facilitate the emergence of abnormal
behaviours after treatment with pramipexole. The patient's abnormal behaviours,
such as eating other patients' food and taking her medicine before the scheduled
time, might differ from typical compulsive behaviours induced by pramipexole
(such as pathological gambling and hypersexuality), but they could be regarded as
disinhibition. Therefore, we should follow up on the clinical course of this case
carefully through neuroimaging investigation and neurocognitive assessment.
PMID- 26419317
TI - Heat-shock pretreatment reduces expression and release of TSLP from keratinocytes
under Th2 environment.
AB - BACKGROUND: Atopic dermatitis is a chronic, relapsing inflammatory disease of the
skin. Current therapy is not curative, and recalcitrant disease is a big stress
and challenge for parents and physicians. This study explored the potential role
of heat-shock protein 70 (HSP-70) and its anti-inflammatory effects on
keratinocyte under TH2 environment. METHODS: Human keratinocyte cell line (HaCa
T) was stimulated with IL-4, IL-13, and TNF-alpha to synthesize and secrete
thymic stromal lymphopoietin (TSLP), an important cytokine of immunopathogenesis
in atopic dermatitis. Heat shock was performed by immersing the cell-contained
flash into a water bath of 45 degrees C for 20 min. Cell viability, TSLP
expression, and secretion of HaCa T cells were measured and compared. Possible
regulatory mechanisms influencing the expression of TSLP, such as the STAT6 and
NF-kappaB signal pathways, were investigated. RESULTS: Heat-shock treatment
induced intracellular HSP-70 expression in HaCa T cells without affecting cell
viability. The induced expression and secretion of TSLP in HaCa T cells were
suppressed by heat shock. The NF-kappaB signal pathway was inhibited by heat
shock, leading to decreased TSLP expression and secretion. CONCLUSION: Heat
stress-induced HSPs can significantly reduce the production and secretion of TSLP
from HaCaT cells under Th2 environment. Thus, the evidence highlights the
potential role of HSP-70 for atopic dermatitis in the future.
PMID- 26419316
TI - Ethanol Enhances TGF-beta Activity by Recruiting TGF-beta Receptors From
Intracellular Vesicles/Lipid Rafts/Caveolae to Non-Lipid Raft Microdomains.
AB - Regular consumption of moderate amounts of ethanol has important health benefits
on atherosclerotic cardiovascular disease (ASCVD). Overindulgence can cause many
diseases, particularly alcoholic liver disease (ALD). The mechanisms by which
ethanol causes both beneficial and harmful effects on human health are poorly
understood. Here we demonstrate that ethanol enhances TGF-beta-stimulated
luciferase activity with a maximum of 0.5-1% (v/v) in Mv1Lu cells stably
expressing a luciferase reporter gene containing Smad2-dependent elements. In
Mv1Lu cells, 0.5% ethanol increases the level of P-Smad2, a canonical TGF-beta
signaling sensor, by ~ 2-3-fold. Ethanol (0.5%) increases cell-surface expression
of the type II TGF-beta receptor (TbetaR-II) by ~ 2-3-fold from its intracellular
pool, as determined by I(125) -TGF-beta-cross-linking/Western blot analysis.
Sucrose density gradient ultracentrifugation and indirect immunofluorescence
staining analyses reveal that ethanol (0.5% and 1%) also displaces cell-surface
TbetaR-I and TbetaR-II from lipid rafts/caveolae and facilitates translocation of
these receptors to non-lipid raft microdomains where canonical signaling occurs.
These results suggest that ethanol enhances canonical TGF-beta signaling by
increasing non-lipid raft microdomain localization of the TGF-beta receptors.
Since TGF-beta plays a protective role in ASCVD but can also cause ALD, the TGF
beta enhancer activity of ethanol at low and high doses appears to be responsible
for both beneficial and harmful effects. Ethanol also disrupts the location of
lipid raft/caveolae of other membrane proteins (e.g., neurotransmitter, growth
factor/cytokine, and G protein-coupled receptors) which utilize lipid
rafts/caveolae as signaling platforms. Displacement of these membrane proteins
induced by ethanol may result in a variety of pathologies in nerve, heart and
other tissues.
PMID- 26419320
TI - Femoral nerve blocks for fractured neck of femur patients: A 'feel good solution'
but a 'short-term fix'?
AB - OBJECTIVE: Femoral nerve blocks (FNBs) are commonly administered to patients with
a fractured neck of femur (NOF). FNBs reduce complications associated with
opioids and are effective for up to 24 h. However, the recognised 'gold standard'
time to definitive treatment (surgery) in the patient with a fractured NOF is
within 48 h. This leaves a significant period of time in which the patient has no
effective analgesia, and might require opioids to alleviate pain. The present
study explored the number of NOF patients who received a FNB: their wait for
definitive treatment (surgery) and how much opioid analgesia was administered in
the preoperative phase. METHODS: A retrospective review of electronic patient
records was conducted over a 6 month period in 2012. Patients who presented to
the ED with a fractured NOF, received a FNB and were transferred to surgery in
the same hospital were included in the sample. RESULTS: The median time from FNBs
to surgery was 37.5 h. When patients waited more than 20 h for surgery, the
volume of opioid received increased significantly (P <= 0.001). CONCLUSION: Even
when patients' time to surgery was within the 'gold standard', patients received
increasing doses of opioids 20 h after the administration of the FNB. While
patients continue to wait extended periods for surgery, the practice of
administering a single injection FNB needs to be challenged. ED clinicians might
consider FNB infusions rather than single injection FNBs for patients with a
fractured NOF.
PMID- 26419321
TI - Evidence supporting vertical transmission of Salmonella in dairy cattle.
AB - We set out to investigate whether Salmonella enterica could be recovered from
various tissues of viable neonatal calves immediately following parturition.
Eleven samples were aseptically collected from each of 20 calves and consisted of
both left and right subiliac and prescapular lymph nodes (LN), mesenteric LN,
spleen and liver, as well as intestinal tissue (including luminal contents) from
the small intestine, caecum, spiral colon and rectum. In addition, a faecal
sample was collected from 19 of the dams. Salmonella was recovered from at least
one sample from 10 of the 20 neonates. Across all calves, Salmonella was
recovered from 12.7% of all samples and from LN in particular, Salmonella was
recovered from 10.0%, 5.0%, and 5.0% of subiliac, prescapular, and mesenteric LN,
respectively. Within calves, Salmonella was recovered from 0% to 73% of samples
and across tissues, estimates of Salmonella prevalence were greatest in the
caecum (30%) but was never recovered from the right pre-scapular LN. These data
provide evidence of vertical transmission from a dam to her fetus such that
viable calves are born already infected and thereby not requiring faecal-oral
exposure for transmission. This new knowledge ought to challenge - or at least
add to - existing paradigms of Salmonella transmission dynamics within cattle
herds.
PMID- 26419322
TI - Nitric oxide is involved in brassinosteroid-induced alternative respiratory
pathway in Nicotiana benthamiana seedlings' response to salt stress.
AB - Recent studies reported that brassinosteroids (BRs) can induce plant tolerance to
different environmental stresses via the nitric oxide (NO) signaling pathway.
Previous reports have indicated that alternative oxidase (AOX) plays an important
role in plants under various stresses. The mechanisms governing how NO is
involved as a signal molecule which connects BR with AOX in regulating stress
tolerance are still unknown. Recently, we found that Nicotiana benthamiana
seedlings which were pretreated with BR have more tolerance to salt stress,
accompanied with an increase of CN-resistant respiration. Our results suggested
that pretreatment with 0.1 MUM brassinolide (BL, the most active brassinosteroid)
alleviated salt-induced oxidative damage and increased the NbAOX1 transcript
level. Application of 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-1
oxyl-3-oxide (cPTIO, an NO scavenger) or virus-induced gene silencing of nitrate
reductase (NR) and nitric oxide synthase (NOS)-like enzyme compromised the BRs
induced alternative respiratory pathway. Furthermore, pretreatment with specific
chemical inhibitors of NR and NOS or gene silencing experiments decreased plant
resistance to salt stress which also compromised BRs-induced salt stress
tolerance. In conclusion, NO is involved in BRs-induced AOX capability which
plays essential roles in salt tolerance in N. benthamiana seedlings.
PMID- 26419323
TI - The effects of environmental enrichment and transport stress on the weights of
lymphoid organs, cell-mediated immune response, heterophil functions and antibody
production in laying hens.
AB - The effects of environmental enrichment and transport stress on the immune system
were investigated in laying hens. A total of 48 1-day-old chickens were used,
half of the chickens were reared in conventional cages (RCC) and the rest in
enriched cages (REC). Transport stress was applied in the 17th week. Liver weight
decreased, spleen and bursa of Fabricius weights, white blood cell count, CD4+
and CD8+ cell proportions increased due to the transport. Environmental
enrichment significantly increased antibody production and tended to increase
monocyte percentage and CD8+ cell proportion. The effect of transport on,
heterophil (H) and lymphocyte (L) percentages was not significant in RCC
chickens. While heterophil percentage and H:L ratio increased, lymphocyte
percentage decreased in REC chickens subjected to transport. Transport stress
increased heterophil functions both in REC and RCC chickens, but the increase was
higher in REC hens than in RCC hens. In conclusion, although environmental
enrichment did not neutralize the effect of transport on lymphoid organs, it
activated the non-specific immune system, cellular and the humoral branches of
the specific immune system by increasing heterophil functions, CD8+ cells and
antibody production, respectively. Therefore, environmental enrichment suggested
for improving animal welfare may also be beneficial to improve the immune system
of birds exposed to stress.
PMID- 26419324
TI - Do the levels of tumor makers or proinflammatory cytokines in mid-trimester
cervical fluid predict early-stage cervical shortening?
AB - AIM: In the present study, we aimed to assess the biomarkers in mid-trimester
cervical fluid that can predict early stage cervical shortening. MATERIAL AND
METHODS: We obtained cervical swab specimens from 96 gravidas, after which the
cervical length was measured, at approximately 20 weeks of gestation. Cervical
length was measured again at 4 weeks after the initial examination. Cervical
shortening was noted in 20 women between 20 and 24 weeks of gestation (group A),
whereas no cervical shortening was noted in 76 women (group B). We evaluated the
use of the levels of tumor markers, proinflammatory cytokines, and matrix
metalloproteinase-8 (MMP-8) as candidate biomarkers. CA-125 and carcinoembryonic
antigen levels were determined by using an automatic immunoassay system in both
groups. Furthermore, IL-1beta, IL-8, tumor necrosis factor-alpha, and MMP-8
levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The
levels of inflammatory cytokines and MMP-8 did not differ between the two groups,
and were not correlated with cervical length or the change in cervical length.
Although CA-125 and carcinoembryonic antigen levels were higher in group A, they
were not statistically significant (P = 0.304 and 0.092, respectively).
CONCLUSION: Early stage cervical shortening in mid-trimester was not associated
with an increase in the levels of tumor markers or proinflammatory cytokines in
cervical fluid.
PMID- 26419325
TI - Occurrence, activity and contribution of anammox in some freshwater extreme
environments.
AB - Anaerobic ammonium oxidation (anammox) widely occurs in marine ecosystems, and it
plays an important role in the global nitrogen cycle. But in freshwater
ecosystems its occurrence, distribution and contribution, especially in extreme
environments, are still not well known. In this study, anammox process was
investigated in some extreme environments of freshwater ecosystems, such as those
with high (above 75 degrees C) and low (below -35 degrees C) temperature, high
(pH > 8) and low (pH < 4) pH and eutrophy (the concentration of NH4 (+) -N > 300
mg kg(-1) ). The polymerase chain reaction (PCR) screening results showed that
anammox bacteria were widespread in the examined sediments from freshwater
extreme environments. Quantitative PCR showed that the abundance of anammox
bacteria ranged from 6.94 * 10(4) to 8.05 * 10(6) hydrazine synthase (hzsB) gene
copies g(-1) dry soil. (15) N-labelled incubation experiments indicated the
occurrence of anammox in all examined sediments and the potential anammox rates
ranged from 0.02 to 6.24 nmol N g(-1) h(-1) , with a contribution of 3.45-58.74%
of the total N2 production. In summary, these results demonstrate the occurrence
of anammox in these extreme environments, inferring that anammox may harbour a
wide ecological niche in the freshwater ecosystems.
PMID- 26419327
TI - To ask, or not to ask: the hesitation process described by district nurses
encountering women exposed to intimate partner violence.
AB - AIMS AND OBJECTIVES: To improve the understanding of district nurses' experiences
of encountering women exposed to intimate partner violence. BACKGROUND: Intimate
partner violence is a public health issue that influences all aspects of affected
women's lives; it is thus of great relevance to identify intimate partner
violence. District nurses in primary health care in Sweden encounter women of all
ages and are therefore in a unique position to identify intimate partner violence
and provide nursing care. However, studies indicate that several barriers have
kept nurses from identifying intimate partner violence. Consequently deeper
understanding of district nurses' encounters with women exposed to intimate
partner violence is needed. DESIGN: A qualitative study using grounded theory
method. METHODS: Interviews with 11 district nurses in primary health care in
Sweden. RESULTS: The hesitation process is central in these encounters. Several
barriers to asking and factors that facilitated asking impacted the hesitation
process. Under the influence of these factors, district nurses moved from being
unaware that identifying intimate partner violence was their professional
responsibility, to becoming ambivalent about asking, to starting to prepare
themselves to ask about intimate partner violence. The presence of factors that
facilitated asking finally made district nurses feel prepared, and then they
decided to ask women about intimate partner violence. CONCLUSIONS: The concept of
managing the hesitation process could be used to be incorporated in continuing
education and training. Barriers and facilitators concerning organisational
factors found in this study may be specific to the Swedish health care system,
but the concept of the hesitation process is applicable in similar contexts and
perhaps to other issues about which it is difficult to ask. RELEVANCE TO CLINICAL
PRACTICE: This study illuminates the importance of a supportive work environment
in reducing district nurses' hesitation to ask about intimate partner violence
and to propose continuing education, training and supervision for district nurses
regarding intimate partner violence.
PMID- 26419326
TI - A novel PIGN mutation and prenatal diagnosis of inherited
glycosylphosphatidylinositol deficiency.
AB - Glycosylphosphatidylinositol (GPI) anchors tether proteins to the extracellular
face of eukaryotic plasma membranes. Defects in the human GPI anchor biosynthetic
pathway cause inherited GPI deficiencies (IGDs) characterized by multiple
congenital anomalies: dysmorphic faces, developmental delay, hypotonia, and
epilepsy. We report the case of a 6-year-old boy with severe psychomotor
developmental delay, epilepsy, and decreased granulocyte surface expression of
GPI-anchored protein that suggested autosomal recessive GPI deficiency. The case
underwent target exome sequencing to screen for IGDs. Target exome sequencing of
the proband identified an apparently homozygous c.808T > C (p.Ser270Pro) mutation
in PIGN, a gene involved in the GPI anchor biosynthetic pathway. As his parents
were expecting another child, genetic carrier screening was conducted for the
parents. Direct sequencing of the parents identified a heterozygous c.808T > C
PIGN mutation in the father but none in the mother. To identify the mother's
mutation, we performed semi-quantitative real-time PCR of the PIGN exons and long
PCR, identifying a microdeletion in PIGN (del exons 2-14). The proband had
inherited this microdeletion from his mother. Prenatal diagnosis of the fetus
revealed that it was a heterozygous carrier of the mother's pathogenic allele.
Here, we report a sporadic case of inherited GPI deficiency with a PIGN mutation
and the first case of prenatal diagnosis for GPI deficiency.
PMID- 26419328
TI - Ablative fractional laser resurfacing with topical paromomycin as adjunctive
treatment for a recalcitrant cutaneous leishmaniasis wound.
AB - BACKGROUND AND OBJECTIVE: Leishmaniasis is a vector borne disease that can cause
disease manifestations that range from localized skin ulceration to lethal
visceral disease. With increased global travel, cutaneous leishmaniasis (CL) is
becoming more common in developed nations. However, current treatment options are
limited. STUDY DESIGN: We report a 16-year-old female who presented with several
non-tender, non-healing CL wounds on her bilateral upper and lower extremities.
Ablative fractional laser resurfacing (AFR) was used in conjunction with topical
paromomycin via laser-assisted delivery to treat the largest non-healing CL wound
on the patient's distal lower extremity. RESULTS: Upon follow-up after two
treatments with AFR, the patient's wound healed completely without evidence of
infection and with minimal scarring. CONCLUSION: AFR with laser-assisted delivery
of topical paromomycin represents a novel treatment option for resistant, non
healing CL wounds. The technique may prove additionally useful for concurrent
mitigation of scarring related to CL.
PMID- 26419329
TI - The drug situation in Europe: an overview of data available on illicit drugs and
new psychoactive substances from European monitoring in 2015.
AB - AIM: A central task for the European Monitoring Centre for Drugs and Drug
Addiction (EMCDDA) is to produce an annual report of the latest data available on
drug demand and drug supply in Europe. This paper is intended to facilitate a
better understanding of, and easier access to, the main quantitative European
level data sets available in 2015. METHODS: The European reporting system
formally covers all 28 European Union (EU) Member States, Norway and Turkey and
incorporates multiple indicators alongside an early warning system (EWS) on
uncontrolled new psychoactive substances (NPS). While epidemiological information
is based largely on registries, surveys and other routine data reported annually,
the EWS collects case-based data on an ongoing basis. The 2015 reporting exercise
is centred primarily on a set of standardized reporting tools. RESULTS: The most
recent data provided by European countries are presented, including data on drug
use, drug-related morbidity and mortality, treatment demand, drug markets and new
psychoactive substances, with data tables provided and methodological
information. A number of key results are highlighted for illustrative purposes.
Drug prevalence estimates from national surveys since 2012 (last year prevalence
of use among the 15-34 age band) range from 0.4% in Turkey to 22.1% in France for
cannabis, from 0.2% in Greece and Romania to 4.2% in the United Kingdom for
cocaine, from 0.1% in Italy and Turkey to 3% in the Czech Republic and the United
Kingdom for ecstasy, and from 0.1% or less in Romania, Italy and Portugal to 2.5%
in Estonia for amphetamine. Declining trends in new HIV detections among people
who inject drugs are illustrated, in addition to presentation of a breakdown of
NPS reported to the EU early warning system, which have risen exponentially from
fewer than 20 a year between 2005 and 2008, to 101 reported in 2014. CONCLUSIONS:
Structured information is now available on patterns and trends in drug
consumption in Europe, which permits triangulation of data from different sources
and consideration of methodological limitations. Opioid drugs continue to place a
burden on the drug treatment system, although both new heroin entrants and
injecting show declines. More than 450 new psychoactive substances are now
monitored by the European early warning system with 31 new synthetic cathinones
and 30 new synthetic cannabinoid receptor agonists notified in 2014.
PMID- 26419331
TI - Yeast nitrogen catabolite repression is sustained by signals distinct from
glutamine and glutamate reservoirs.
AB - Nitrogen catabolite repression (NCR) is a wide transcriptional regulation program
enabling baker's yeast to downregulate genes involved in the utilization of poor
nitrogen sources when preferred ones are available. Nowadays, glutamine and
glutamate, the major nitrogen donors for biosyntheses, are assumed to be key
metabolic signals regulating NCR. NCR is controlled by the conserved TORC1
complex, which integrates nitrogen signals among others to regulate cell growth.
However, accumulating evidence indicate that the TORC1-mediated control of NCR is
only partial, arguing for the existence of supplementary regulatory processes to
be discovered. In this work, we developed a genetic screen to search for new
players involved in NCR signaling. Our data reveal that the NADP-glutamate
dehydrogenase activity of Gdh1 negatively regulates NCR-sensitive gene
transcription. By determining the total, cytoplasmic and vacuolar pools of amino
acids, we show that there is no positive correlation between glutamine/glutamate
reservoirs and the extent of NCR. While our data indicate that glutamine could
serve as initial trigger of NCR, they show that it is not a sufficient signal to
sustain repression and point to the existence of yet unknown signals. Providing
additional evidence uncoupling TORC1 activity and NCR, our work revisits the
dogmas underlying NCR regulation.
PMID- 26419330
TI - Limited dissemination of the wastewater treatment plant core resistome.
AB - Horizontal gene transfer is a major contributor to the evolution of bacterial
genomes and can facilitate the dissemination of antibiotic resistance genes
between environmental reservoirs and potential pathogens. Wastewater treatment
plants (WWTPs) are believed to play a central role in the dissemination of
antibiotic resistance genes. However, the contribution of the dominant members of
the WWTP resistome to resistance in human pathogens remains poorly understood.
Here we use a combination of metagenomic functional selections and comprehensive
metagenomic sequencing to uncover the dominant genes of the WWTP resistome. We
find that this core resistome is unique to the WWTP environment, with <10% of the
resistance genes found outside the WWTP environment. Our data highlight that,
despite an abundance of functional resistance genes within WWTPs, only few genes
are found in other environments, suggesting that the overall dissemination of the
WWTP resistome is comparable to that of the soil resistome.
PMID- 26419332
TI - The structure of Legionella pneumophila LegK4 type four secretion system (T4SS)
effector reveals a novel dimeric eukaryotic-like kinase.
AB - Bacterial pathogens subvert signalling pathways to promote invasion and/or
replication into the host. LegK1-4 proteins are eukaryotic-like serine/threonine
kinases that are translocated by the Dot/Icm type IV secretion system (T4SS) of
several Legionella pneumophila strains. We present the crystal structures of an
active fragment of the LegK4 protein in apo and substrate-bound states. The
structure of LegK4(1-445) reveals a eukaryotic-like kinase domain flanked by a
novel cap domain and a four-helix bundle. The protein self-assembles through
interactions mediated by helices alphaF and alphaG that generate a dimeric
interface not previously observed in a protein kinase. The helix alphaG is
displaced compared to previous kinase structures, and its role in stabilization
of the activation loop is taken on by the dimerisation interface. The apo-form of
the protein has an open conformation with a disordered P-loop but a structured
activation segment in absence of targeted phosphorylation. The nucleotide-binding
site of LegK4 contains an unusual set of residues that mediate non-canonical
interactions with AMP-PNP. Nucleotide binding results in limited changes in the
active site, suggesting that LegK4 constitutive kinase activity does not depend
on phosphorylation of the activation loop but on the stabilizing effects of the
dimer.
PMID- 26419333
TI - Extracellular vesicles are rapidly purified from human plasma by PRotein Organic
Solvent PRecipitation (PROSPR).
AB - Extracellular vesicles (EVs) such as exosomes and microvesicles mediate
intercellular communication and regulate a diverse range of crucial biological
processes. Host cells that are damaged, infected or transformed release biomarker
containing EVs into the peripheral circulation, where they can be readily
accessed for use in diagnostic or prognostic testing. However, current methods of
EV isolation from blood plasma are complex and often require relatively large
sample volumes, hence are inefficient for widespread use in clinical settings.
Here, we report a novel and inexpensive method of rapidly isolating EVs from
small volumes of human blood plasma by PRotein Organic Solvent PRecipitation
(PROSPR). PROSPR encompasses a rapid three-step protocol to remove soluble
proteins from plasma via precipitation in cold acetone, leaving the lipid
encapsulated EVs behind in suspension. This generates higher purity EVs that can
then be obtained from filtration or classical ultracentrifugation methods. We
foresee that PROSPR-based purification of EVs will significantly accelerate the
discovery of new disease biomarkers and the characterization of EVs with
potential for clinical applications.
PMID- 26419334
TI - Photon Harvesting in Sunscreen-Based Functional Nanoparticles.
AB - The ultraviolet light component in the solar spectrum is known to cause several
harmful effects, such as allergy, skin ageing, and skin cancer. Thus, current
research attention has been paid to the design and fundamental understanding of
sunscreen-based materials. One of the most abundantly used sunscreen molecules is
Avobenzone (AB), which exhibits two tautomers. Here, we highlight the preparation
of spherically shaped nanoparticles from the sunscreen molecule AB as well as
from sunscreen-molecule-encapsulated polymer nanoparticles in aqueous media and
study their fundamental photophysical properties by steady-state and time
resolved spectroscopy. Steady-state studies confirm that the AB molecule is in
the keto and enol forms in tetrahydrofuran, whereas the enol form is stable in
the case of both AB nanoparticles and AB-encapsulated poly(methyl methacrylate)
(PMMA) nanoparticles. Thus, the keto-enol transformation of AB molecules is
restricted to a nanoenvironment. An enhancement of photostability in both the
nanoparticle and PMMA-encapsulated forms under UV light irradiation is observed.
The efficient excited energy transfer (60 %) from AB to porphyrin molecules opens
up further prospects in potential applications as light-harvesting systems.
PMID- 26419335
TI - Transcriptome analysis of hormone-induced gene expression in Brachypodium
distachyon.
AB - Brachypodium distachyon is a new model plant closely related to wheat and other
cereals. In this study, we performed a comprehensive analysis of hormone
regulated genes in Brachypodium distachyon using RNA sequencing technology.
Brachypodium distachyon seedlings were treated with eight phytohormones (auxin,
cytokinine, brassinosteroid, gibberelline, abscisic acid, ethylene, jasmonate and
salicylic acid) and two inhibitors, Brz220 (brassinosteroid biosynthesis
inhibitor) and prohexadione (gibberelline biosynthesis inhibitor). The
expressions of 1807 genes were regulated in a phytohormone-dependent manner. We
compared the data with the phytohormone responses that have reported in rice.
Transcriptional responses to hormones are conserved between Bracypodium and rice.
Transcriptional regulation by brassinosteroid, gibberellin and ethylene was
relatively weaker than those by other hormones. This is consistent with the data
obtained from comprehensive analysis of hormone responses reported in
Arabidopsis. Brachypodium and Arabidopsis also shared some common transcriptional
responses to phytohormones. Alternatively, unique transcriptional responses to
phytohormones were observed in Brachypodium. For example, the expressions of ACC
synthase genes were up-regulated by auxin treatment in rice and Arabidopsis, but
no orthologous ACC synthase gene was up-regulated in Brachypodium. Our results
provide information useful to understand the diversity and similarity of hormone
regulated transcriptional responses between eudicots and monocots.
PMID- 26419337
TI - Selection of pairings reaching evenly across the data (SPREAD): A simple
algorithm to design maximally informative fully crossed mating experiments.
AB - We present a novel algorithm for the design of crossing experiments. The
algorithm identifies a set of individuals (a 'crossing-set') from a larger pool
of potential crossing-sets by maximizing the diversity of traits of interest, for
example, maximizing the range of genetic and geographic distances between
individuals included in the crossing-set. To calculate diversity, we use the mean
nearest neighbor distance of crosses plotted in trait space. We implement our
algorithm on a real dataset of Neurospora crassa strains, using the genetic and
geographic distances between potential crosses as a two-dimensional trait space.
In simulated mating experiments, crossing-sets selected by our algorithm provide
better estimates of underlying parameter values than randomly chosen crossing
sets.
PMID- 26419336
TI - Ancestral whole-genome duplication in the marine chelicerate horseshoe crabs.
AB - Whole-genome duplication (WGD) results in new genomic resources that can be
exploited by evolution for rewiring genetic regulatory networks in organisms. In
metazoans, WGD occurred before the last common ancestor of vertebrates, and has
been postulated as a major evolutionary force that contributed to their
speciation and diversification of morphological structures. Here, we have
sequenced genomes from three of the four extant species of horseshoe crabs
Carcinoscorpius rotundicauda, Limulus polyphemus and Tachypleus tridentatus.
Phylogenetic and sequence analyses of their Hox and other homeobox genes, which
encode crucial transcription factors and have been used as indicators of WGD in
animals, strongly suggests that WGD happened before the last common ancestor of
these marine chelicerates >135 million years ago. Signatures of
subfunctionalisation of paralogues of Hox genes are revealed in the appendages of
two species of horseshoe crabs. Further, residual homeobox pseudogenes are
observed in the three lineages. The existence of WGD in the horseshoe crabs,
noted for relative morphological stasis over geological time, suggests that
genomic diversity need not always be reflected phenotypically, in contrast to the
suggested situation in vertebrates. This study provides evidence of ancient WGD
in the ecdysozoan lineage, and reveals new opportunities for studying genomic and
regulatory evolution after WGD in the Metazoa.
PMID- 26419339
TI - Polysorbate 20 Degradation in Biopharmaceutical Formulations: Quantification of
Free Fatty Acids, Characterization of Particulates, and Insights into the
Degradation Mechanism.
AB - Polysorbate 20 (PS20), a commonly used surfactant in biopharmaceuticals, showed
degradation upon long-term (~18-36 months) storage of two monoclonal antibody
(mAb, mAb-A, and mAb-B) drug products at 2-8 degrees C. The PS20 degradation
resulted in the accumulation of free fatty acids (FFA), which ultimately
precipitated to form particles upon long-term storage. This study documents the
development, qualification, and application of a method for FFA quantification in
soluble and insoluble fraction of protein formulation. The method was applied to
the quantification of capric acid, lauric acid, myristic acid, palmitic/oleic
acid, and stearic acid in placebo as well as active protein formulations on
stability. Quantification of FFA in both the soluble and insoluble fraction of
mAb-A and mAb-B provided a better mechanistic understanding of PS20 degradation
and the dynamics of subsequent fatty acid particle formation. Additionally, the
use of this method for monitoring and quantitation of the FFA on real time
storage stability appears to aid in identifying batches with higher probability
for particulate formation upon extended storage at 5 degrees C.
PMID- 26419338
TI - Microguards and micromessengers of the genome.
AB - The regulation of gene expression is of fundamental importance to maintain
organismal function and integrity and requires a multifaceted and highly ordered
sequence of events. The cyclic nature of gene expression is known as
'transcription dynamics'. Disruption or perturbation of these dynamics can result
in significant fitness costs arising from genome instability, accelerated ageing
and disease. We review recent research that supports the idea that an important
new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the
genome against short-term transcriptional fluctuations, in a process we term
'microguarding'. An additional emerging role for miRNAs is as 'micromessengers'
through alteration of gene expression in target cells to which they are
trafficked within microvesicles. We describe the scant but emerging evidence that
miRNAs can be moved between different cells, individuals and even species, to
exert biologically significant responses. With these two new roles, miRNAs have
the potential to protect against deleterious gene expression variation from
perturbation and to themselves perturb the expression of genes in target cells.
These interactions between cells will frequently be subject to conflicts of
interest when they occur between unrelated cells that lack a coincidence of
fitness interests. Hence, there is the potential for miRNAs to represent both a
means to resolve conflicts of interest, as well as instigate them. We conclude by
exploring this conflict hypothesis, by describing some of the initial evidence
consistent with it and proposing new ideas for future research into this exciting
topic.
PMID- 26419340
TI - Kinetics and Mechanisms of Ciprofloxacin Oxidation on Hematite Surfaces.
AB - Adsorption of antibiotics at mineral surfaces has been extensively studied over
the past 20 years, yet much remains to be learned on their interfacial properties
and transformation mechanisms. In this study, interactions of Ciprofloxacin
(CIP), a fluoroquinolone antibiotic with two sets of synthetic nanosized hematite
particles, with relatively smooth (H10, 10-20 nm in diameter) and roughened (H80,
80-90 nm in diameter) surfaces, were studied by means of liquid chromatography
(LC), mass spectrometry (MS), and spectroscopy (vibration and X-ray
photoelectron). Attenuated Total Reflectance Fourier Transform Infrared (ATR
FTIR) spectroscopy provides evidence for inner-sphere bidentate complex formation
of CIP at hematite surfaces in 0.01 M NaCl, irrespective of pH and particle size.
ATR-FTIR spectroscopy also revealed that the sorbed mother CIP molecule decayed
to other surface species over a period of at least 65 h. This was supported by
the detection of three daughter products in the aqueous phase by LC/MS. The
appearance of NH3(+) groups during the course of these experiments, revealed by
cryogenic XPS, provides further evidence that CIP oxidation proceeds through an
opening of piperazine ring via N-dealkylation. Additional in vacuo FTIR
experiments under temperature-programmed desorption also showed that oxidation of
sorbed byproducts were effectively degraded beyond 450 degrees C, a result
denoting considerably strong (inter)molecular bonds of both mother and daughter
products. This work also showed that rougher, possibly multidomainic particles
(H80) generated slower rates of CIP decomposition but occurring through more
complex schemes than at smoother particle surfaces (H10). This work thus
uncovered key aspects of the binding of an important antibiotic at iron oxide
surfaces, and therefore provided additional constraints to our growing
understanding of the fate of emerging contaminants in the environment.
PMID- 26419341
TI - Palladium-catalyzed cross-coupling reaction of azides with isocyanides.
AB - An efficient palladium-catalyzed cross-coupling reaction of azides with
isocyanides is developed, providing a general synthetic route to unsymmetric
carbodiimides with excellent yields. This method shows a broad substrate scope,
including not only aryl azides, but also unactivated benzyl and alkyl azides.
Furthermore, from readily available substrates, Pd-catalyzed coupling with a
tandem amine insertion cascade to obtain unsymmetric trisubstituted guanidines
has been achieved in a one-pot fashion.
PMID- 26419342
TI - A novel mutation in CEBPA gene in a patient with acute myeloid leukemia.
PMID- 26419343
TI - Genetic parameters and signatures of selection in two divergent laying hen lines
selected for feather pecking behaviour.
AB - BACKGROUND: Feather pecking (FP) in laying hens is a well-known and multi
factorial behaviour with a genetic background. In a selection experiment, two
lines were developed for 11 generations for high (HFP) and low (LFP) feather
pecking, respectively. Starting with the second generation of selection, there
was a constant difference in mean number of FP bouts between both lines. We used
the data from this experiment to perform a quantitative genetic analysis and to
map selection signatures. METHODS: Pedigree and phenotypic data were available
for the last six generations of both lines. Univariate quantitative genetic
analyses were conducted using mixed linear and generalized mixed linear models
assuming a Poisson distribution. Selection signatures were mapped using 33,228
single nucleotide polymorphisms (SNPs) genotyped on 41 HFP and 34 LFP individuals
of generation 11. For each SNP, we estimated Wright's fixation index (FST). We
tested the null hypothesis that FST is driven purely by genetic drift against the
alternative hypothesis that it is driven by genetic drift and selection. RESULTS:
The mixed linear model failed to analyze the LFP data because of the large number
of 0s in the observation vector. The Poisson model fitted the data well and
revealed a small but continuous genetic trend in both lines. Most of the 17
genome-wide significant SNPs were located on chromosomes 3 and 4. Thirteen
clusters with at least two significant SNPs within an interval of 3 Mb maximum
were identified. Two clusters were mapped on chromosomes 3, 4, 8 and 19. Of the
17 genome-wide significant SNPs, 12 were located within the identified clusters.
This indicates a non-random distribution of significant SNPs and points to the
presence of selection sweeps. CONCLUSIONS: Data on FP should be analysed using
generalised linear mixed models assuming a Poisson distribution, especially if
the number of FP bouts is small and the distribution is heavily peaked at 0. The
FST-based approach was suitable to map selection signatures that need to be
confirmed by linkage or association mapping.
PMID- 26419344
TI - In vitro methods for screening transdermal formulations.
AB - This article provides a review of the critical in vitro assays utilized in
transdermal drug development. In vitro assays such as percutaneous absorption
testing and dissolution (drug release) testing are powerful tools for screening
potential transdermal compounds and drug quality control, respectively. Several
2D single-cell cultures and 3D human skin equivalents are available for screening
compounds with low irritation and sensitization potential. The role of each assay
and its limitations and challenges will be further discussed below.
PMID- 26419345
TI - Relationship between strenuous exercise and cardiac "morbimortality": Benefits
outweigh the potential risks.
PMID- 26419346
TI - Concise access to iminophosphonamide stabilized heteroleptic germylenes: chemical
reactivity and structural investigation.
AB - The influence of a sterically demanding iminophosphonamide ligand, [(2,6
iPr2C6H3N)P(Ph2)(NtBu)]H (LH), on the synthesis and stability of a heteroleptic
germylene monochloride, [(2,6-iPr2C6H3N)P(Ph2)(NtBu)]GeCl (1), and its reaction
chemistry has been discussed. Complex 1 behaves as a Lewis base to form an adduct
with Fe(CO)4, namely [(2,6-iPr2C6H3N)P(Ph2)(NtBu)]Ge(Cl)Fe(CO)4 (2). Reaction of
1 with KOtBu or AgOSO2CF3 affords Ge(ii) compounds, [(2,6
iPr2C6H3N)P(Ph2)(NtBu)]GeR (R = OtBu (3), OSO2CF3 (4)). Treatment of complex 1
with elemental sulfur or selenium leads to heavier analogues of germaacid
chlorides, [(2,6-iPr2C6H3N)P(Ph2)(NtBu)]Ge(E)Cl (E = S (5), Se (6)). Similarly,
compound 3 on reaction with elemental sulfur or selenium produces heavier
analogues of germaesters, [(2,6-iPr2C6H3N)P(Ph2)(NtBu)]Ge(E)OtBu (E = S (7), Se
(8)). Complexes 1-8 were characterized using multinuclear NMR and EI-MS, and
solid state structures of complexes 1-3, 5 and 8 have been elucidated using
single crystal X-ray diffraction.
PMID- 26419348
TI - The intersection of global health with cancer control.
PMID- 26419347
TI - Studies of trypanosomiasis in the Luangwa valley, north-eastern Zambia.
AB - BACKGROUND: The present study, conducted in Zambia's Luangwa valley where both
animal African trypanosomiasis (AAT) and human African trypanosomiasis (HAT) are
endemic, combined the use of microscopy and molecular techniques to determine the
presence of trypanosome species in cattle, goats and tsetse flies. METHODS: This
study was conducted between 2008 and 2010 in Petauke, Chama and Isoka districts,
north-eastern Zambia. A total of 243 cattle, 36 goats and 546 tsetse flies, were
examined for presence of trypanosome species using microscopy, PCR and loop
mediated isothermal amplification (LAMP). RESULTS: There was poor agreement among
the test methods used for detection of trypanosomes species in animal blood and
tsetse flies. Trypanosomes were observed in 6.1 % (95 % CI: 3.3-8.9 %) of the
animals sampled by microscopy, 7.5 % (95 % CI: 4.4-10.6 %) by PCR and 18.6 % (95
% CI: 13.6-23.6 %) by PFR-LAMP. PFR-LAMP was more sensitive for detecting
Trypanozoon than KIN-PCR. The highest occurrence of AAT was recorded in cattle
from Petauke (58.7 %, 95 % CI: 44.7-72.7 %) while the lowest was from Isoka (5.4
%, 95 % CI: 0.8-10.0 %). Infection of both cattle and goats with Trypanosoma
congolense and T. vivax was associated with clinical AAT. CONCLUSION: When
selecting molecular techniques for AAT surveillance in endemic regions, the KIN
PCR and species-specific PCR may be recommended for screening animal or tsetse
fly samples for T. congolense and T. vivax, respectively. On the other hand,
species-specific PCR and/or LAMP might be of greater value in the screening of
animal and human body fluids as well as tsetse fly samples for Trypanozoon.
PMID- 26419349
TI - Global Task Force on Radiotherapy for Cancer Control.
PMID- 26419350
TI - The verdict is in: the time for effective solutions to the global cancer burden
is now.
PMID- 26419351
TI - Expanding global access to radiotherapy: the European Society for Radiotherapy
and Oncology perspective.
PMID- 26419352
TI - Radiotherapy in southeast Asia: room to grow.
PMID- 26419353
TI - Expanding global access to radiotherapy: the IAEA perspective.
PMID- 26419354
TI - Expanding global access to radiotherapy.
AB - Radiotherapy is a critical and inseparable component of comprehensive cancer
treatment and care. For many of the most common cancers in low-income and middle
income countries, radiotherapy is essential for effective treatment. In high
income countries, radiotherapy is used in more than half of all cases of cancer
to cure localised disease, palliate symptoms, and control disease in incurable
cancers. Yet, in planning and building treatment capacity for cancer,
radiotherapy is frequently the last resource to be considered. Consequently,
worldwide access to radiotherapy is unacceptably low. We present a new body of
evidence that quantifies the worldwide coverage of radiotherapy services by
country. We show the shortfall in access to radiotherapy by country and globally
for 2015-35 based on current and projected need, and show substantial health and
economic benefits to investing in radiotherapy. The cost of scaling up
radiotherapy in the nominal model in 2015-35 is US$26.6 billion in low-income
countries, $62.6 billion in lower-middle-income countries, and $94.8 billion in
upper-middle-income countries, which amounts to $184.0 billion across all low
income and middle-income countries. In the efficiency model the costs were lower:
$14.1 billion in low-income, $33.3 billion in lower-middle-income, and $49.4
billion in upper-middle-income countries-a total of $96.8 billion. Scale-up of
radiotherapy capacity in 2015-35 from current levels could lead to saving of 26.9
million life-years in low-income and middle-income countries over the lifetime of
the patients who received treatment. The economic benefits of investment in
radiotherapy are very substantial. Using the nominal cost model could produce a
net benefit of $278.1 billion in 2015-35 ($265.2 million in low-income countries,
$38.5 billion in lower-middle-income countries, and $239.3 billion in upper
middle-income countries). Investment in the efficiency model would produce in the
same period an even greater total benefit of $365.4 billion ($12.8 billion in low
income countries, $67.7 billion in lower-middle-income countries, and $284.7
billion in upper-middle-income countries). The returns, by the human-capital
approach, are projected to be less with the nominal cost model, amounting to
$16.9 billion in 2015-35 (-$14.9 billion in low-income countries; -$18.7 billion
in lower-middle-income countries, and $50.5 billion in upper-middle-income
countries). The returns with the efficiency model were projected to be greater,
however, amounting to $104.2 billion (-$2.4 billion in low-income countries,
$10.7 billion in lower-middle-income countries, and $95.9 billion in upper-middle
income countries). Our results provide compelling evidence that investment in
radiotherapy not only enables treatment of large numbers of cancer cases to save
lives, but also brings positive economic benefits.
PMID- 26419355
TI - Characterization of DNA aptamers generated against the soft-shelled turtle
iridovirus with antiviral effects.
AB - BACKGROUND: Soft-shelled turtle iridovirus (STIV) causes severe systemic disease
in farmed soft-shelled turtles (Trionyx sinensis). More efficient methods of
controlling and detecting STIV infections are urgently needed. METHODS: In this
study, we generated eight single-stranded DNA (ssDNA) aptamers against STIV using
systematic evolution of ligands by exponential enrichment (SELEX). RESULTS: The
aptamers formed representative stem-loop secondary structures. Electrophoretic
mobility shift assays and fluorescent localization showed that the selected
aptamers had high binding affinity for STIV. Aptamer QA-36 had the highest
calculated binding affinity (K d ) of 53.8 nM. Flow cytometry and fluorescence
microscopy of cell-aptamer interactions demonstrated that QA-12 was able to
recognize both STIV-infected cells and tissues with a high level of specificity.
Moreover, the selected aptamers inhibited STIV infection in vitro and in vivo,
with aptamer QA-36 demonstrating the greatest protective effect against STIV and
inhibiting STIV infection in a dose-dependent manner. DISCUSSION: We generated
DNA aptamers that bound STIV with a high level of specificity, providing an
alternative means for investigating STIV pathogenesis, drug development, and
medical therapies for STIV infection. CONCLUSIONS: These DNA aptamers may thus be
suitable antiviral candidates for the control of STIV infections.
PMID- 26419357
TI - Evidence for disrupted gray matter structural connectivity in posttraumatic
stress disorder.
AB - Posttraumatic stress disorder (PTSD) is characterized by atrophy within the
prefrontal-limbic network. Graph analysis was used to investigate to what degree
atrophy in PTSD is associated with impaired structural connectivity within
prefrontal limbic network (restricted) and how this affects the integration of
the prefrontal limbic network with the rest of the brain (whole-brain). 85 male
veterans (45 PTSD neg, 40 PTSD pos) underwent volumetric MRI on a 3T MR. Subfield
volumes were obtained using a manual labeling scheme and cortical thickness
measurements and subcortical volumes from FreeSurfer. Regression analysis was
used to identify regions with volume loss. Graph analytical Toolbox (GAT) was
used for graph-analysis. PTSD pos had a thinner rostral anterior cingulate and
insular cortex but no hippocampal volume loss. PTSD was characterized by
decreased nodal degree (orbitofrontal, anterior cingulate) and clustering
coefficients (thalamus) but increased nodal betweenness (insula, orbitofrontal)
and a reduced small world index in the whole brain analysis and by orbitofrontal
and insular nodes with increased nodal degree, clustering coefficient and nodal
betweenness in the restricted analysis. PTSD associated atrophy in the prefrontal
limbic network results in an increased structural connectivity within that
network that negatively affected its integration with the rest of the brain.
PMID- 26419356
TI - Positive Emotions Program for Schizophrenia (PEPS): a pilot intervention to
reduce anhedonia and apathy.
AB - BACKGROUND: Recent literature has distinguished the negative symptoms associated
with a diminished capacity to experience (apathy, anhedonia) from symptoms
associated with a limited capacity for expression (emotional blunting, alogia).
The apathy-anhedonia syndrome tends to be associated with a poorer prognosis than
the symptoms related to diminished expression. The efficacy of drug-based
treatments and psychological interventions for these symptoms in schizophrenia
remains limited. There is a clear clinical need for new treatments. METHODS: This
pilot study tested the feasibility of a program to reduce anhedonia and apathy in
schizophrenia and assessed its impact on 37 participants meeting the ICD-10
criteria for schizophrenia or schizoaffective disorders. Participants were pre-
and post-tested using the Scale for the Assessment of Negative Symptoms (SANS)
and the Calgary Depression Scale for Schizophrenia (CDSS). They took part in
eight sessions of the Positive Emotions Program for Schizophrenia (PEPS)--an
intervention that teaches participants skills to help overcome defeatist thinking
and to increase the anticipation and maintenance of positive emotions. RESULTS:
Thirty-one participants completed the program; those who dropped out did not
differ from completers. Participation in the program was accompanied by
statistically significant reductions in the total scores for Avolition-Apathy and
Anhedonia-Asociality on the SANS, with moderate effect sizes. Furthermore, there
was a statistically significant reduction of depression on the CDSS, with a large
effect size. Emotional blunting and alogia remain stable during the intervention.
DISCUSSION: Findings indicate that PEPS is both a feasible intervention and is
associated with an apparently specific reduction of anhedonia and apathy.
However, these findings are limited by the absence of control group and the fact
that the rater was not blind to the treatment objectives. CONCLUSIONS: PEPS is a
promising intervention to improve anhedonia and apathy which need to be tested
further in a controlled study. TRIAL REGISTRATION NUMBER: ISRCTN registry
ISRCTN74048461, registered 18 may 2015.
PMID- 26419359
TI - Para- and perirenal ultrasonographic fat thickness is associated with 24-hours
mean diastolic blood pressure levels in overweight and obese subjects.
AB - BACKGROUND: Renal sinus fat (RSF) has been recognized as a risk factor for
arterial hypertension. This study was addressed to examine whether also para- and
perirenal fat accumulation is associated to higher 24-h mean systolic (SBP)
and/or diastolic blood pressure (DBP) levels in overweight and obese subjects.
METHODS: A cohort of 42 overweight and obese patients, 29 women and 13 men, aged
25-55 years, not treated with any kind of drug, was examined. Body mass index
(BMI), waist circumference (WC), fasting insulin and glucose serum levels,
insulin resistance (assessed by using the homeostasis model assessment [HOMAIR]),
and 24-h aldosterone urine levels were measured. Ambulatory blood pressure
monitoring (ABPM) was measured with 15 min intervals from 7.0 a.m. to 11.0 a.m.
and with 30 min intervals from 23.0 to 7.0 for consecutive 24 h, starting from
8:30 AM. Measurement of para- and perirenal fat thickness was performed by
ultrasounds by a duplex Doppler apparatus. RESULTS: Para- and perirenal
ultrasonographic fat thickness (PUFT) was significantly and positively correlated
with WC (p < 0.01), insulin (p < 0.01), HOMAIR (p < 0.01), and 24-h mean DBP
levels (p < 0.05). 24-h mean DBP was also significantly and positively correlated
with 24-h aldosterone urine concentrations (p < 0.001). A multivariate analysis
by multiple linear regression was performed; the final model showed that the
association of 24-h mean DBP as dependent variable with PUFT (multiple R = 0.34;
p = 0.026) and daily aldosterone production (multiple R = 0.59; p = 0.001) was
independent of other anthropometric, hormone and metabolic parameters. DISCUSSION
AND CONCLUSIONS: This study shows a positive independent association between PUFT
and mean 24-h diastolic blood pressure levels in overweight and obese subjects,
suggesting a possible direct role of PUFT in increasing daily diastolic blood
pressure.
PMID- 26419360
TI - Epidemiology of hepatitis A virus in Africa among persons aged 1-10 years: a
systematic review protocol.
AB - BACKGROUND: Africa is considered an area of high endemicity for hepatitis A virus
infection. However, in the past two decades, tremendous progress has been made in
improving water sources and sanitation which are risk factors for hepatitis A
virus infection. Recent studies suggest that several African countries could be
in epidemiological transitions due to the evident socio-economic development. As
a result, there may be a decrease in the exposure to and infection with hepatitis
A virus at an early age. Understanding and mapping the shifting epidemiology is
vital in developing control measures against the disease. We are conducting a
comprehensive systematic review study to document the current burden of hepatitis
A virus infection in Africa. METHODS: Our population of interest is children
between 1 and 10 years in any African country. We will select cross-sectional,
case-control, and cohort studies that have tested hepatitis A virus infection by
serological confirmation of antibodies against the virus. We will search for
eligible studies published without language restrictions from PubMed, Scopus,
Africa-wide, Web of Science, and WHOLIS as well as the reference lists of the
relevant articles. Two authors will independently review the search outputs,
select eligible articles, and extract pre-defined study outcomes. Inconsistencies
will be resolved by discussion and consensus among the authors. Data will be
extracted using a standardised data collection form. Trends in the prevalence
and/or incidence will be evaluated by urban and rural setting if sufficient data
is available. Where there is sufficient homogeneity between studies, meta
analysis will also be conducted, otherwise the results will be presented in a
narrative format. DISCUSSION: The systematic review will generate up-to-date
information on the current burden of hepatitis A virus in Africa. This
information may have implications on policy for hepatitis A vaccination on
individual African countries. SYSTEMATIC REVIEW REGISTRATION: CRD42015023764.
PMID- 26419358
TI - Prevalence of chronic periodontitis in an obese population: a preliminary study.
AB - BACKGROUND: Chronic periodontitis (CP) is a global public health issue. Studies
have suggested CP could be linked to obesity due to their similar
pathophysiological pathway. The aim of this study is to determine the prevalence
of CP and to assess the predictors for CP among the obese Malaysian population.
METHODS: This is a cross-sectional study on obese participants. Obesity is
defined as an individual who has Body Mass Index (BMI) >= 27.5 kg/m(2). A
convenience sampling method was used. A total of 165 paricipants were recruited.
This study involved answering questionnaires, obtaining biometric and clinical
measurements of Visible plaque index (VPI), Gingival bleeding index (GBI),
Probing pocket depth (PPD) and Clinical attachment loss (CAL). Data analysis was
carried out using SPSS statistical software (SPSS Inc., version 20, US). RESULTS:
A total of 165 participants; 67 (40.6%) males and 98 (59.4%) females participated
in the study. Mean age of the participants was 43.9 (+/- 8.9). The prevalence of
CP among the obese population was found to be 73.9%. Out of this, 43 and 55% were
categorised as moderate and severe CP respectively. Around 64% of participants
had sites with CAL >= 4 mm and participants with sites with PPD >= 4 mm were
reported to be 25%. Around 83% of the participants had sites with GBI >= 30 and
92% of participants had sites with VPI >= 20%. GBI and VPI were found to have
significantly higher odds for CP. CONCLUSION: Prevalence of CP was high among
obese Malaysians. GBI and VPI were potential predictors for CP in this obese
population.
PMID- 26419361
TI - Resection of metachronous pancreatic cancer 4 years after pancreaticoduodenectomy
for stage III pancreatic adenocarcinoma.
AB - Pancreatic adenocarcinoma frequently recurs in patients even after resection with
curative intent. The majority of these are early recurrences and are associated
with metastatic disease, thus not amenable to repeat resection. Here we report a
patient who underwent completion pancreatectomy for a metachronous pancreatic
adenocarcinoma. This patient initially presented with painless jaundice and
computed tomography (CT) revealed a mass in the head of the pancreas. Brushings
obtained at endoscopic retrograde cholangiopancreatography (ERCP) were positive
for adenocarcinoma. This patient then underwent a Whipple procedure and final
pathology demonstrated stage III pancreatic ductal adenocarcinoma. Adjuvant
therapy included gemcitabine and erlotinib. This patient was followed with
physical examinations and serial laboratory and imaging studies. There was no
evidence of disease for four years at which time and sharp elevation in CA-19-9
was found. Subsequent imaging revealed a mass in the remnant pancreas. Curative
intent completion pancreatectomy was then performed which confirmed the presence
of pancreatic adenocarcinoma. This was followed by adjuvant Gemcitabine based
chemotherapy and chemoradiation. One year later the patient is alive with no
evidence of disease. Thus, in highly selected patients with recurrent or
metachronous pancreatic cancer, repeat pancreatectomy can be considered, but the
course of treatment should be considered in a multidisciplinary setting.
PMID- 26419362
TI - Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms.
AB - Tylosis (hyperkeratosis palmaris et plantaris) is characterised by focal
thickening of the skin of the hands and feet and is associated with a very high
lifetime risk of developing squamous cell carcinoma of the oesophagus. This risk
has been calculated to be 95% at the age of 65 in one large family, however the
frequency of the disorder in the general population is not known and is likely to
be less than one in 1,000,000. Oesophageal lesions appear as small (2-5 mm),
white, polyploid lesions dotted throughout the oesophagus and oral leukokeratosis
has also been described. Although symptoms of oesophageal cancer can include
dysphagia, odynophagia, anorexia and weight loss, there may be an absence of
symptoms in early disease, highlighting the importance of endoscopic surveillance
in these patients. Oesophageal cancer associated with tylosis usually presents in
middle to late life (from mid-fifties onwards) and shows no earlier development
than the sporadic form of the disease. Tylosis with oesophageal cancer is
inherited as an autosomal dominant trait with complete penetrance of the
cutaneous features, usually by 7 to 8 years of age but can present as late as
puberty. Mutations in RHBDF2 located on 17q25.1 have recently been found to be
causative. A diagnosis of tylosis with oesophageal cancer is made on the basis of
a positive family history, characteristic clinical features, including cutaneous
and oesophageal lesions, and genetic analysis for mutations in RHBDF2. The key
management goal is surveillance for early detection and treatment of oesophageal
dysplasia. Surveillance includes annual gastroscopy with biopsy of any suspicious
lesion together with quadratic biopsies from the upper, middle and lower
oesophagus. This is coupled with dietary and lifestyle modification advice and
symptom education. Symptomatic management of the palmoplantar keratoderma
includes regular application of emollients, specialist footwear and early
treatment of fissures and super-added infection, particularly tinea pedis. More
specific treatment for the thick skin is available in the form of oral retinoids,
which are very effective but commonly produce side effects, including nasal
excoriation and bleeding, hypercholesterolaemia, and abnormal liver function
tests. Genetic counselling can be offered to patients and family members once a
family history has been established. The prognosis of tylosis with oesophageal
cancer is difficult to determine due to the limited number of affected
individuals. In the last 40 years of surveillance, five out of six cases of
squamous oesophageal cancer in the Liverpool family were detected endoscopically
and were surgically removed. Four of five patients had stage 1 disease at
presentation and remain alive and well more than 8 years later. This suggests
that the presence of a screening program improves prognosis for these patients.
PMID- 26419363
TI - Vitamin D supplementation improves well-being in patients with frequent
respiratory tract infections: a post hoc analysis of a randomized, placebo
controlled trial.
AB - BACKGROUND: The aim of this study was to test the hypothesis that vitamin D
supplementation improves well-being in patients with frequent respiratory tract
infections (RTIs). We performed a post hoc analysis of a randomized, placebo
controlled and double-blind study in which patients with frequent RTIs were
randomized to placebo or vitamin D (4000 IE/day for 1 year, n = 124). At the last
visit of the study, patients were asked to perform a general assessment of their
well-being during the study. RESULTS: The majority of patients, both placebo- and
vitamin D treated, stated that they had felt 'better' during the study; 52% in
the placebo group and 70% in the vitamin D group, relative risk 1.3 (95% CI 1.0
1.8; p = 0.06, Fisher's exact test). Statement of better well-being was
associated with an increase in 25-hydroxyvitamin D (25-OHD) levels (p < 0.001).
In contrast, worse well-being was associated with unchanged 25-OHD levels.
Notably, a 25-OHD level above 100 nmol/L at the study end was associated with a
higher chance of having a better well-being (p < 0.01). Four patients on anti
depressive treatment could terminate their antidepressant medication during the
study. These patients had a significant increase in 25-OHD levels from low levels
at study-start. CONCLUSION: Vitamin D supplementation to patients with frequent
RTIs might be beneficial, not only for infections, but also for their general
well-being. However, given the post hoc design of this study, these findings need
to be confirmed in additional clinical trials before firm conclusions can be
drawn. TRIAL REGISTRATION: http://www.clinicaltrials.gov (NCT01131858),
registered March 22, 2010.
PMID- 26419364
TI - Slowly progressive Lemierre's syndrome with orbital pain and exophthalmos.
AB - Lemierre's syndrome is an oropharyngeal bacterial infection characterized by
rapidly progressive septic thrombophlebitis of the internal jugular vein. A lack
of appropriate antibiotic therapy can be life-threatening. We describe the case
of a 39-year-old man with Lemierre's syndrome who presented with long-lasting
orbital pain and acute exophthalmos 6 weeks after initial infection. This report
is to help clinicians consider the diagnosis of Lemierre's syndrome when
encountering a patient with long-lasting orbital pain and acute exophthalmos.
Neck ultrasonography is useful for detecting thrombophlebitis of the internal
jugular vein in Lemierre's syndrome patients.
PMID- 26419366
TI - High-throughput screening identified inherited genetic variations in the EGFR
pathway contributing to skin toxicity of EGFR inhibitors.
AB - AIM: To identify genomic variants in the EGFR pathway and in cytokines
predisposing to skin toxicity from EGFR inhibitors. PATIENTS & METHODS: In 126
patients with cancer and EGFR inhibitor therapy skin toxicity was quantified and
EGFR and inflammatory pathway genes were analyzed by deep sequencing. RESULTS: We
found 1437 SNPs in the 382-kb target region. Three SNPs in EGFR intron 1 were
found exclusively in patients without skin rash. Another EGFR intron 23 SNP was
associated with skin rash, overall survival and IL8 plasma concentrations.
Moreover, carriers of the PIK3R1 326I variant were predisposed to skin rash and
better survival. CONCLUSION: Comprehensive pathway-based resequencing revealed
some new but only moderately strong genomic predictors of skin toxicity.
PMID- 26419373
TI - The pack size effect: Influence on consumer perceptions of portion sizes.
AB - Larger portions as well as larger packs can lead to larger prospective
consumption estimates, larger servings and increased consumption, described as
'portion-size effects' and 'pack size effects'. Although related, the effects of
pack sizes on portion estimates have received less attention. While it is not
possible to generalize consumer behaviour across cultures, external cues taken
from pack size may affect us all. We thus examined whether pack sizes influence
portion size estimates across cultures, leading to a general 'pack size effect'.
We compared portion size estimates based on digital presentations of different
product pack sizes of solid and liquid products. The study with 13,177
participants across six European countries consisted of three parts. Parts 1 and
2 asked participants to indicate the number of portions present in a combined
photographic and text-based description of different pack sizes. The estimated
portion size was calculated as the quotient of the content weight or volume of
the food presented and the number of stated portions. In Part 3, participants
stated the number of food items that make up a portion when presented with packs
of food containing either a small or a large number of items. The estimated
portion size was calculated as the item weight times the item number. For all
three parts and across all countries, we found that participants' portion
estimates were based on larger portions for larger packs compared to smaller
packs (Part 1 and 2) as well as more items to make up a portion (Part 3); hence,
portions were stated to be larger in all cases. Considering that the larger
estimated portions are likely to be consumed, there are implications for energy
intake and weight status.
PMID- 26419375
TI - IgG N-Glycosylation Galactose Incorporation Ratios for the Monitoring of
Classical Galactosaemia.
AB - Classical galactosaemia (OMIM #230400) is a rare disorder of carbohydrate
metabolism caused by deficiency of the galactose-1-phosphate uridyltransferase
enzyme (EC 2.7.7.12). The cause of the long-term complications, including
neurological, cognitive and fertility problems in females, remains poorly
understood. The relatively small number of patients with galactosaemia and the
lack of validated biomarkers pose a substantial challenge for determining
prognosis and monitoring disease progression and responses to new therapies. We
report an improved method of automated robotic hydrophilic interaction ultra
performance liquid chromatography N-glycan analysis for the measurement of IgG N
glycan galactose incorporation ratios applied to the monitoring of adult patients
with classical galactosaemia. We analysed 40 affected adult patients and 81
matched healthy controls. Significant differences were noted between the G0/G1
and G0/G2 incorporation ratios between galactosaemia patients and controls (p <
0.001 and <0.01, respectively). Our data indicate that the use of IgG N
glycosylation galactose incorporation analysis may be now applicable for
monitoring patient dietary compliance, determining prognosis and the evaluation
of potential new therapies.
PMID- 26419376
TI - A Review of Recent Literature on Trauma Among Individuals Living with HIV.
AB - Persons living with HIV (PLWH) report disproportionately high levels of exposure
to traumatic events in childhood and adulthood. Traumatic experiences are
associated with negative health and behavioral outcomes. Current research in this
area seeks to further explicate the myriad health effects of trauma on PLWH and
the pathways through which trauma operates. In this paper, we review articles
published in English between January 2014 and June 2015 that examine traumatic
experiences among PLWH, including intimate partner violence (IPV), domestic
abuse, child abuse, and other forms of violence. A selection of studies examining
trauma among PLWH and its associations with mental health, antiretroviral
medication adherence, clinical outcomes, HIV disclosure, and sexual risk
behaviors were included. Studies describing trauma coping strategies and
interventions were also included. We conclude with recommendations for care of
trauma-exposed PLWH and directions for future research.
PMID- 26419377
TI - Are pelvic anatomical structures in danger during arthroscopic acetabular labral
repair? Definition of safe bone depth.
AB - PURPOSE: The purpose of this study was to evaluate safe depth for suture anchor
insertion during acetabular labral repair and to determine the neighbouring
structures at risk during drilling and anchor insertion. METHODS: Ten human
cadaveric hips (six males and four females) were obtained. Acetabular labral
surface was prepared and marked for right hips as 12, 1 and 3 o'clock positions,
for left hips 12, 11 and 9 o'clock positions. Those were defined as anterior,
anterior-superior and superior zones, respectively. These labral positions were
drilled at defined zones. After measurements, depth of the bone at 10 degrees
and 20 degrees drill angles on zones was compared statistically. RESULTS:
Acetabular bone widths at investigated labral insertion points did not
statistically differ. A total of 14 injuries in 60 penetrations occurred (23.3 %)
with free drill penetrations, and no injuries occurred with stopped drill
penetrations. The bone depth was gradually decreasing from 10 degrees to 20
degrees drill angles and from anterior to superior inserting zones without
significant importance. The risk of perforation to the pelvic cavity started with
20 mm drill depth, and the mean depth for all insertions was calculated as 31.7
mm (SD 2.6). CONCLUSIONS: It is anatomically possible that some pelvic structures
sustain iatrogenic injury during acetabular drilling for anchor placement. Being
aware of mean pelvic vault is important in which drilling after excessive pincer
rim trimming could easily decrease the depth of acetabular bone without a
standard. Careful drilling by using stopped drill bit is crucial to prevent
iatrogenic injury.
PMID- 26419378
TI - Arthroscopic-assisted plate fixation for displaced large-sized comminuted greater
tuberosity fractures of proximal humerus: a novel surgical technique.
AB - PURPOSE: The purpose of the present study was to describe the use of a novel
hybrid surgical technique-arthroscopic-assisted plate fixation-and evaluate its
clinical and anatomical outcomes in the management of large, displaced greater
tuberosity (GT) fractures with comminution. METHODS: From 2009 to 2011, this
novel technique was performed in 11 patients [2 men and 9 women; median age, 64
years (range 41-83 years)] with large, comminuted GT fractures, with fragment
displacements of >5 mm. The preoperative mean posterior and superior migration of
the fractured fragment, as measured on computed tomography (CT), was 19.5 and 5.5
mm, respectively. Two patients had shoulder fracture-dislocation, and three had
associated undisplaced surgical neck fracture. The mean duration between injury
and surgery was 4 days. The mean follow-up duration was 26 months. RESULTS: At
the final follow-up, the mean postoperative ASES, UCLA and SST scores were 84,
29, and 8, respectively. The mean range of motion was as follows: forward
flexion, 138 degrees ; abduction, 135 degrees ; external rotation at the side, 19
degrees ; and internal rotation, up to the L2 level. The mean posterior and
superior displacements of fracture fragments on postoperative CT scan [0.7 +/-
0.8 mm (range 0-2.1 mm) and 2.8 +/- 0.5 mm (range 3.4-5.3 mm), respectively] were
significantly improved (p < 0.05). On arthroscopy, a partial articular-side
supraspinatus tendon avulsion lesion was identified in 10 of 11 patients (91 %),
and 1 of these patients had a partial tear of the biceps and 1 had a partial
subscapularis tear, respectively (9 %). Intraoperatively, 1 anchor pullout and 1
anchor protrusion through the humeral head were noted and corrected.
Postoperatively, the loss of reduction in the fracture fragment was noted in 1
patient at 4 weeks, after corrective reduction and fixation surgery. CONCLUSIONS:
The novel arthroscopic-assisted anatomical plate fixation technique was found to
be effective in reducing large-sized, displaced, comminuted GT fractures and in
allowing concurrent management of intra-articular pathologies and early
functional rehabilitation. Compared with the conventional plate fixation or
arthroscopic suture anchor fixation technique, arthroscopic-assisted plate
fixation enabled accurate restoration of the medial footprint of the GT fracture
and provided an effective buttress to the large-sized GT fracture fragments.
LEVEL OF EVIDENCE: Retrospective clinical study, Level IV.
PMID- 26419379
TI - Regional differences in temperature course after knee arthroplasty.
AB - PURPOSE: During wound healing after surgery, physiological inflammation leads to
an increase in soft tissue perfusion. This is reflected by a characteristic
temperature course in the skin. Although local surgical trauma also influences
soft tissue perfusion, no data have been available on the regional temperature
distribution after knee arthroplasty to date. This study aims at testing the
hypothesis that the greatest regional difference in the temperature course is on
the site of the maximum surgical trauma (medially) after knee arthroplasty
implantation. This is to our knowledge the first study to present regional
differences in the temperature course after TKA which would limit the diagnostic
value of thermography. METHODS: Forty-two subjects who were to receive a surface
replacement of the knee joint due to primary varus gonarthrosis were included in
the study. In all cases, a medial parapatellar approach was chosen. Patients who
underwent lateral release or a release of the lateral ligament structures were
excluded. In all patients, a thermographic temperature determination was carried
out on the operated knee joint every day up to the seventh post-operative day.
RESULTS: On the medial side, there was no significant change in temperature
between day one 34.9 degrees +/- 0.2 degrees (34.6-35.3 degrees C) and seven
after surgery. Thereafter, the temperature remained constant here up to the
seventh day after the operation. In contrast to this, on the lateral side there
was an increase in skin temperature from the second 35.0 +/- 0.2 degrees C (34.7
35.4 degrees C) to the fifth 34.6 degrees +/- 0.2 degrees (34.1-34.9 degrees
C) post-operative day (p = 0.002). Thereafter, the temperature remained constant
here up to the seventh day after the operation. CONCLUSION: This study refutes
the hypothesis that the greatest regional difference in the temperature course is
on the site of maximum surgical trauma (medially) after knee arthroplasty
implantation. It is shown to the contrary that there is the least regional
difference in the temperature course on the site of maximum surgical trauma
(medially) after total knee arthroplasty implantation. It is on the site of the
minimal trauma (laterally) where marked differences in the temperature course
appeared. The normal temporary temperature increase typical of physiological
wound healing could only be shown at a distance from the site of soft tissue
preparation. This may be the result of a local compromise of perfusion.
Consequently, the post-operative diagnostic application of thermography remains
limited to regions distant from the surgical site. This may prevent
misinterpretation of post-operative thermographic measurements for scientific or
clinical reasons. LEVEL OF EVIDENCE: II.
PMID- 26419380
TI - High prevalence of multiple-antibiotic-resistant (MAR) Escherichia coli in river
bed sediments of the Apies River, South Africa.
AB - This study aimed at investigating the presence of antibiotic-resistant
Escherichia coli in river bed sediments of the Apies River, Gauteng, South
Africa, in order to better inform health management decisions designed to protect
users of the river. Overall, 180 water and sediment samples were collected at 10
sites along the Apies River from January to February 2014. E. coli was enumerated
using the Colilert(r) 18/Quanti-Tray(r) 2000 (IDEXX). Isolates were purified by
streaking on eosin methylene blue agar followed by the indole test. Pure E. coli
isolates were tested for resistance to nine antibiotics by the Kirby-Bauer disc
diffusion method. Over 98% of the isolates were resistant to at least one of the
antibiotics tested. The highest resistance was observed against nitrofurantoin
(sediments) and ampicillin (water). Over 80% of all resistant isolates showed
multiple antibiotic resistance (resistance to >=3 antibiotics). The abundance of
E. coli in the sediments not only adds to the evidence that sediments are a
reservoir for bacteria and possibly other pathogens including antibiotic
resistant bacteria but also suggests that antibiotic-resistant genes could be
transferred to pathogens due to the high prevalence of multiple-antibiotic
resistant (MAR) strains of E. coli observed in the sediment. Using untreated
water from the Apies River following resuspension for drinking and other
household purposes could pose serious health risks for users. Our results suggest
that river bed sediments could serve as reservoirs for MAR bacteria including
pathogens under different climatic conditions and their analysis could provide
information of public health concerns.
PMID- 26419381
TI - Mercury concentrations and health risk assessment for two fish species, Barbus
grypus and Barbus luteus, from the Maroon River, Khuzestan Province, Iran.
AB - The purposes of this study are to investigate the concentration of mercury in
edible muscle tissues of two popular edible fish species: the Shirbot (Barbus
grypus) and Hemri (Barbus luteus), from the Maroon River, Khuzestan Province,
Iran, and to assess the risk of their toxicity on human health. We collected 20
samples of each species from the river, and after biometry and determination of
their age and sex, concentration of total mercury (assumed to be about 100%
methylmercury) was measured. For B. grypus, mercury averaged 0.16 +/- 0.02 MUg g(
1) wet weight, and for B. luteus, it averaged 0.08 +/- 0.02 MUg g(-1) wet weight.
Although mercury has been reported to accumulate with age, length, and trophic
level in many studies, we did not find a significant correlation among age, sex,
length, and mercury content in either of these omnivorous species. Mercury levels
(maximum 0.37 MUg g(-1) wet weight) were below international standards.
Consumption of these fish would not pose a serious health hazard to Iranian
consumers at the average national consumption of 17.53 g day(-1). However, high
end consumers eating more than 250 g week(-1) and pregnant women should be
attentive in choosing fish low in mercury, for example, B. luteus rather than B.
grypus.
PMID- 26419382
TI - Sequence and structure-based comparative analysis to assess, identify and improve
the thermostability of penicillin G acylases.
AB - Penicillin acylases are enzymes employed by the pharmaceutical industry for the
manufacture of semi-synthetic penicillins. There is a continuous demand for
thermostable and alkalophilic enzymes in such applications. We have carried out a
computational analysis of known penicillin G acylases (PGAs) in terms of their
thermostable nature using various protein-stabilizing factors. While the presence
of disulfide bridges was considered initially to screen putative thermostable
PGAs from the database, various other factors such as high arginine to lysine
ratio, less content of thermolabile amino acids, presence of proline in beta
turns, more number of ion-pair and other non-bonded interactions were also
considered for comparison. A modified consensus approach designed could further
identify stabilizing residue positions by site-specific comparison between
mesostable and thermostable PGAs. A most likely thermostable enzyme identified
from the analysis was PGA from Paracoccus denitrificans (PdPGA). This was cloned,
expressed and tested for its thermostable nature using biochemical and
biophysical experiments. The consensus site-specific sequence-based approach
predicted PdPGA to be more thermostable than Escherichia coli PGA, but not as
thermostable as the PGA from Achromobacter xylosoxidans. Experimental data showed
that PdPGA was comparatively less thermostable than Achromobacter xylosoxidans
PGA, although thermostability factors favored a much higher stability. Despite
being mesostable, PdPGA being active and stable at alkaline pH is an advantage.
Finally, several residue positions could be identified in PdPGA, which upon
mutation selectively could improve the thermostability of the enzyme.
PMID- 26419383
TI - Control of carbon flux to glutamate excretion in Klebsiella pneumoniae: the role
of the indigenous plasmid and its encoded isocitrate dehydrogenase.
AB - Klebsiella pneumoniae (NCTC, CL687/80) harbors a large indigenous plasmid
(p(C3)), which in addition to encoding for citrate utilization, proline synthesis
and glutamate excretion, it uniquely carries the structural gene (icd); encoding
isocitrate dehydrogenase (ICDH). Flux analysis revealed that ICDH, despite its
role in the generation of NADPH required for glutamate dehydrogenase, is not rate
limiting (controlling) in central metabolism as evidenced by a negative flux
control coefficient and an adverse effect of overexpression (14-fold) on
glutamate excretion. More significantly, however, this paper presents, for the
first time, clear evidence that the accumulation of glutamate and its subsequent
excretion is associated with the C3 plasmid-encoded regulatory elements, which
trigger a shift-down in the activity of alpha-ketoglutarate dehydrogenase, both
in the K. pneumoniae parental strain as well as in the E. coli exconjugants
strains. This finding opens the door for the exploitation of regulatory elements
as a tool for manipulating flux in microbial cell factories.
PMID- 26419384
TI - What is new about diet in hepatic encephalopathy.
AB - There is a relationship between hepatic encephalopathy (HE) protein malnutrition
and muscle wasting. Muscle may play an alternative role in ammonia
detoxification. Molecular mechanisms responsible for muscle depletion are under
investigation. Specific nutrients may interact to reverse the molecular pathways
involved in muscle wasting at an early stage. Training exercises have also been
proposed to improve skeletal muscle mass. However, these data refer to small
groups of patients. The amelioration of muscle mass may potentially help to
prevent HE. The pathogenesis of HE is associated with modifications of the gut
microbiota and diet is emerging to play a relevant role in the modulation of the
gut milieu. Vegetarian and fibre-rich diets have been shown to induce beneficial
changes on gut microbiota in healthy people, with reduction of Bacteroides spp.,
Enterobacteriaceae, and Clostridium cluster XIVa bacteria. By way of contrast, it
has been suggested that a high-fat or protein diet may increase Firmicutes and
reduce Bacteroidetes phylum. Milk-lysozyme and milk-oligosaccharides have also
been proposed to induce a "healthy" microbiota. At present, no studies have been
published describing the modification of the gut microbiota in cirrhotic patients
with HE as a response to specific diets. New research is needed to evaluate the
potentiality of foods in the modulation of gut microbiota in liver disease and
HE.
PMID- 26419385
TI - Idalopirdine - a small molecule antagonist of 5-HT6 with therapeutic potential
against obesity.
AB - 5HT6 receptor antagonists offer the potential for safe and effective drugs
against obesity, because they can reduce weight without causing serious side
effects in the cardiovascular system. Also, their anorexic effect is associated
with reduced food intake via an enhancement of satiety. In the present study we
investigated the anorexic effect of idalopirdine (LuAE58054) in a model of
obesity induced by high-fat diet. To induce obesity in rats, the animals were
treated with feed with a fat content of 40 %. Body weight was controlled and the
amount of food and water consumed was determined. The influence of the test
compound on the lipid profile and glucose level was measured, as well as
locomotor activity in home cages on the 20th day of the treatment. LuAE58054, at
5 mg kg(-1)/day i.p., was significantly anorectic in this model of obesity.
Animals treated with LuAE58054 weighed 8 and 9.2 % less than the control obese
animals on the 12th and 21st days, respectively. It significantly reduced food
intake and the amount of peritoneal fat in animals, and reduced the level of
triglycerides in plasma. LuAE58054 did not have a statistically significant
effect on the spontaneous activity of diet-induced obese rats. The present study
clearly demonstrates the effectiveness of LuAE58054 in reducing body weight. This
compound is in phase III of clinical trials for the treatment of cognitive
deficits associated with Alzheimer's disease and schizophrenia. It is a 5HT6
receptor antagonist and is, therefore, free of those unacceptable side effects
that preclude chronic use of anti-obesity drugs with other mechanisms of action.
The search for an effective and safe anti-obesity drug is essential for an
increasingly obese population; therefore, the anorectic action of LuAE58054 is
important and there is a need for more research in this direction.
PMID- 26419386
TI - Doppler flowmetry of the superior mesenteric artery and portal vein: impact for
the early prediction of necrotizing enterocolitis in neonates.
AB - PURPOSE: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disorder
in newborns. Early diagnosis and rapid treatment is essential for seeking good
outcome for neonates. The aim of our study was to evaluate intestinal blood flow
in superior mesenteric artery (SMA) and portal vein (PV) in neonates with
suspected or confirmed NEC and investigate the prognostic cut-off values to
develop NEC. METHODS: Doppler flowmetry of SMA and PV was performed for 62
newborns. Resistive (RI) and pulsatility (PI) indexes were measured in SMA as
well as Volumetric blood flow (Vflow) in PV. ROC curves were applied to estimate
sensitivity and specificity and to identify cut-off values. RESULTS: There were
93.5% preterm neonates. 29 patients (46.8%) were diagnosed with NEC and 33
(53.2%) formed a control group. 96.3% NEC patients had RI >0.75 with sensitivity
of 96.3% and specificity of 90.9% (OR 260). 88.9% NEC patients had PI >1.85 with
sensitivity of 88.9% and specificity of 78.8% (OR 29). Portal Vflow lower than 37
ml/min was present in 89.7% patients with NEC (OR 11.7). CONCLUSION: Intestinal
blood flow Dopplerography can be a useful tool for diagnosing and predicting NEC.
PMID- 26419389
TI - Meta-analysis of real-time fMRI neurofeedback studies using individual
participant data: How is brain regulation mediated?
AB - An increasing number of studies using real-time fMRI neurofeedback have
demonstrated that successful regulation of neural activity is possible in various
brain regions. Since these studies focused on the regulated region(s), little is
known about the target-independent mechanisms associated with neurofeedback
guided control of brain activation, i.e. the regulating network. While the
specificity of the activation during self-regulation is an important factor, no
study has effectively determined the network involved in self-regulation in
general. In an effort to detect regions that are responsible for the act of brain
regulation, we performed a post-hoc analysis of data involving different target
regions based on studies from different research groups. We included twelve
suitable studies that examined nine different target regions amounting to a total
of 175 subjects and 899 neurofeedback runs. Data analysis included a standard
first- (single subject, extracting main paradigm) and second-level (single
subject, all runs) general linear model (GLM) analysis of all participants taking
into account the individual timing. Subsequently, at the third level, a random
effects model GLM included all subjects of all studies, resulting in an overall
mixed effects model. Since four of the twelve studies had a reduced field of view
(FoV), we repeated the same analysis in a subsample of eight studies that had a
well-overlapping FoV to obtain a more global picture of self-regulation. The GLM
analysis revealed that the anterior insula as well as the basal ganglia, notably
the striatum, were consistently active during the regulation of brain activation
across the studies. The anterior insula has been implicated in interoceptive
awareness of the body and cognitive control. Basal ganglia are involved in
procedural learning, visuomotor integration and other higher cognitive processes
including motivation. The larger FoV analysis yielded additional activations in
the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal
cortex, the temporo-parietal area and the visual association areas including the
temporo-occipital junction. In conclusion, we demonstrate that several key
regions, such as the anterior insula and the basal ganglia, are consistently
activated during self-regulation in real-time fMRI neurofeedback independent of
the targeted region-of-interest. Our results imply that if the real-time fMRI
neurofeedback studies target regions of this regulation network, such as the
anterior insula, care should be given whether activation changes are related to
successful regulation, or related to the regulation process per se. Furthermore,
future research is needed to determine how activation within this regulation
network is related to neurofeedback success.
PMID- 26419391
TI - How prior expectations shape multisensory perception.
AB - The brain generates a representation of our environment by integrating signals
from a common source, but segregating signals from different sources. This fMRI
study investigated how the brain arbitrates between perceptual integration and
segregation based on top-down congruency expectations and bottom-up stimulus
bound congruency cues. Participants were presented audiovisual movies of
phonologically congruent, incongruent or McGurk syllables that can be integrated
into an illusory percept (e.g. "ti" percept for visual "ki" with auditory /pi/).
They reported the syllable they perceived. Critically, we manipulated
participants' top-down congruency expectations by presenting McGurk stimuli
embedded in blocks of congruent or incongruent syllables. Behaviorally,
participants were more likely to fuse audiovisual signals into an illusory McGurk
percept in congruent than incongruent contexts. At the neural level, the left
inferior frontal sulcus (lIFS) showed increased activations for bottom-up
incongruent relative to congruent inputs. Moreover, lIFS activations were
increased for physically identical McGurk stimuli, when participants segregated
the audiovisual signals and reported their auditory percept. Critically, this
activation increase for perceptual segregation was amplified when participants
expected audiovisually incongruent signals based on prior sensory experience.
Collectively, our results demonstrate that the lIFS combines top-down prior
(in)congruency expectations with bottom-up (in)congruency cues to arbitrate
between multisensory integration and segregation.
PMID- 26419388
TI - Interacting parallel pathways associate sounds with visual identity in auditory
cortices.
AB - Spatial and non-spatial information of sound events is presumably processed in
parallel auditory cortex (AC) "what" and "where" streams, which are modulated by
inputs from the respective visual-cortex subsystems. How these parallel processes
are integrated to perceptual objects that remain stable across time and the
source agent's movements is unknown. We recorded magneto- and
electroencephalography (MEG/EEG) data while subjects viewed animated video clips
featuring two audiovisual objects, a black cat and a gray cat. Adaptor-probe
events were either linked to the same object (the black cat meowed twice in a row
in the same location) or included a visually conveyed identity change (the black
and then the gray cat meowed with identical voices in the same location). In
addition to effects in visual (including fusiform, middle temporal or MT areas)
and frontoparietal association areas, the visually conveyed object-identity
change was associated with a release from adaptation of early (50-150ms) activity
in posterior ACs, spreading to left anterior ACs at 250-450ms in our combined
MEG/EEG source estimates. Repetition of events belonging to the same object
resulted in increased theta-band (4-8Hz) synchronization within the "what" and
"where" pathways (e.g., between anterior AC and fusiform areas). In contrast, the
visually conveyed identity changes resulted in distributed synchronization at
higher frequencies (alpha and beta bands, 8-32Hz) across different auditory,
visual, and association areas. The results suggest that sound events become
initially linked to perceptual objects in posterior AC, followed by modulations
of representations in anterior AC. Hierarchical what and where pathways seem to
operate in parallel after repeating audiovisual associations, whereas the
resetting of such associations engages a distributed network across auditory,
visual, and multisensory areas.
PMID- 26419390
TI - Left ventral occipitotemporal activation during orthographic and semantic
processing of auditory words.
AB - The present fMRI study investigated the hypothesis that activation of the left
ventral occipitotemporal cortex (vOT) in response to auditory words can be
attributed to lexical orthographic rather than lexico-semantic processing. To
this end, we presented auditory words in both an orthographic ("three or four
letter word?") and a semantic ("living or nonliving?") task. In addition, a
auditory control condition presented tones in a pitch evaluation task. The
results showed that the left vOT exhibited higher activation for orthographic
relative to semantic processing of auditory words with a peak in the posterior
part of vOT. Comparisons to the auditory control condition revealed that
orthographic processing of auditory words elicited activation in a large vOT
cluster. In contrast, activation for semantic processing was only weak and
restricted to the middle part vOT. We interpret our findings as speaking for
orthographic processing in left vOT. In particular, we suggest that activation in
left middle vOT can be attributed to accessing orthographic whole-word
representations. While activation of such representations was experimentally
ascertained in the orthographic task, it might have also occurred automatically
in the semantic task. Activation in the more posterior vOT region, on the other
hand, may reflect the generation of explicit images of word-specific letter
sequences required by the orthographic but not the semantic task. In addition,
based on cross-modal suppression, the finding of marked deactivations in response
to the auditory tones is taken to reflect the visual nature of representations
and processes in left vOT.
PMID- 26419392
TI - What Is the Return on Investment for Implementation of a Crew Resource Management
Program at an Academic Medical Center?
AB - Crew Resource Management (CRM) training has been used successfully within
hospital units to improve quality and safety. This article presents a description
of a health system-wide implementation of CRM focusing on the return on
investment (ROI). The costs included training, programmatic fixed costs, time
away from work, and leadership time. Cost savings were calculated based on the
reduction in avoidable adverse events and cost estimates from the literature.
Between July 2010 and July 2013, roughly 3000 health system employees across 12
areas were trained, costing $3.6 million. The total number of adverse events
avoided was 735-a 25.7% reduction in observed relative to expected events.
Savings ranged from a conservative estimate of $12.6 million to as much as $28.0
million. Therefore, the overall ROI for CRM training was in the range of $9.1 to
$24.4 million. CRM presents a financially viable way to systematically organize
for quality improvement.
PMID- 26419393
TI - Topical applications of vitamin D on implant surface for bone-to-implant contact
enhance: a pilot study in dogs part II.
AB - OBJECTIVE: The aim of this study was to evaluate the effect of topical
application of vitamin D over implant surface, placed immediately to the
extraction, throughout histological and histomorphometric analysis of peri
implant tissue. MATERIAL AND METHODS: Six American foxhound dogs were used in the
study. Mandibular premolar distal roots were extracted. Twenty-four immediate
conical C1 implants (MIS, Barlev, Israel) were randomly assigned to the distal
site on each site of the mandible in three groups: (Group CI) 12 titanium
implants alone; (Test Group DI) 12 titanium implants supplemented with vitamin D.
Prior to implanting, test implants (DI) were submerged in vitamin D 10% solution.
No treatment was applied at control implants (CI). After 12 weeks, animals were
sacrificed. Block sections were obtained and processed for mineralized ground
sectioning. Bone-to-implant contact (Total BIC and BIC%), new bone formation
(NBF), interthread bone (ITB), and histological linear measurements (HLM) were
analyzed. RESULTS: At 12 weeks, all implants were clinically stable and
histologically osseointegrated. BIC evaluation showed Total BIC mean and SD
values for DI (48.96 +/- 2.14), CI (44.56 +/- 1.75) (P < 0.05), BIC% DI (43.59 +/
0.98), and CI (42.67 +/- 9.26) (P > 0.05). For interthread bone formation,
values were as follows: DI (15.21 +/- 3.87), CI (14.79 +/- 1.45) (P > 0.05), no
statistically differences. Regarding peri-implant new bone formation, no
statistically differences could be found between the two groups DI (31.87 +/-
1.23), CI (27.18 +/- 2.38) (P > 0.05). For linear measurements, test group (DI)
showed statistically significant less buccal crestal bone loss (CBL) DI (0.37 +/-
0.12)*, CI (1.26 +/- 0.8) (P < 0.05), and vitamin D implants showed less lingual
junctional epithelium DI (1.58 +/- 0.43)*, CI (2.18 +/- 0.48) (P < 0.05). No
differences were observed in the buccal mucosa. CONCLUSION: With the limitation
of animal studies, topical application of vitamin D on dental implants could
reduce crestal bone loss and increase 10% more bone-to-implant contact at 12-week
follow-up period.
PMID- 26419394
TI - Computer aided mammography yields no clear benefit, research finds.
PMID- 26419395
TI - Melt electrospinning of poly(lactic acid) and polycaprolactone microfibers by
using a hand-operated Wimshurst generator.
AB - A conventional melt electrospinning setup usually needs a large, heavy high
voltage power supply and cannot work without a plug (electricity supply). In this
article, we report a new melt electrospinning setup based on a small hand
operated Wimshurst generator, which can avoid electrical interference between the
high-voltage spinning system and the heating system, and make the setup very
portable and safe. Poly(lactic acid) (PLA) and polycaprolactone (PCL) fibers with
diameters of 15-45 MUm were fabricated successfully by using this apparatus.
Experimental parameters such as the rotational speed of the generator handle (a
half turn to two turns per second) and the spinning distance (2-14 cm) were
investigated. In addition, PLA and PCL fibers were directly melt-electrospun onto
a pork liver, and the temperature and adhesiveness of the deposited fibers were
studied. The results indicate that the apparatus and melt-electrospun polymer
microfibers may be used in dressing for wound healing.
PMID- 26419396
TI - Reduction of Saccharomyces cerevisiae Pom34 protein level by SESA network is
related to membrane lipid composition.
AB - Various pathways block initiation of translation of the bulk of mRNAs in response
to membrane stress, amino acid starvation and unfolded proteins. In contrast,
SESA, a network of proteins comprising Smy2, Eap1, Scp160 and Asc1, is a novel
inhibitor of translation initiation of specific mRNAs. SESA binds POM34 mRNA in
response to failure in spindle pole body (SPB) duplication process and inhibits
its initiation of translation. We herein report that Pom34 protein level is
reduced also in cells with altered membrane lipid composition upon treatment with
various chemicals and show that SESA-induced downregulation of Pom34 is crucial
for viability of cells with a disturbed nuclear envelope. Thus, we propose that
SESA's action in SPB duplication process is dependent on the alteration of
membrane lipid composition to facilitate the insertion process.
PMID- 26419397
TI - Single Unit Cell Bismuth Tungstate Layers Realizing Robust Solar CO2 Reduction to
Methanol.
AB - Solar CO2 reduction into hydrocarbons helps to solve the global warming and
energy crisis. However, conventional semiconductors usually suffer from low
photoactivity and poor photostability. Here, atomically-thin oxide-based
semiconductors are proposed as excellent platforms to overcome this drawback. As
a prototype, single-unit-cell Bi2WO6 layers are first synthesized by virtue of a
lamellar Bi-oleate intermediate. The single-unit-cell thickness allows 3-times
larger CO2 adsorption capacity and higher photoabsorption than bulk Bi2WO6. Also,
the increased conductivity, verified by density functional theory calculations
and temperature-dependent resistivities, favors fast carrier transport. The
carrier lifetime increased from 14.7 to 83.2 ns, revealed by time-resolved
fluorescence spectroscopy, which accounts for the improved electron-hole
separation efficacy. As a result, the single-unit-cell Bi2WO6 layers achieve a
methanol formation rate of 75 MUmol g(-1) h(-1), 125-times higher than that of
bulk Bi2WO6. The catalytic activity of the single-unit-cell layers proceeds
without deactivation even after 2 days. This work will shed light on designing
efficient and robust photoreduction CO2 catalysts.
PMID- 26419398
TI - Acute and chronic toxicity of neonicotinoids to nymphs of a mayfly species and
some notes on seasonal differences.
AB - Mayfly nymphs are among the most sensitive taxa to neonicotinoids. The present
study presents the acute and chronic toxicity of 3 neonicotinoids (imidacloprid,
thiacloprid, and thiamethoxam) to a mayfly species (Cloeon dipterum) and some
notes on the seasonality of the toxicity of imidacloprid to C. dipterum and 5
other invertebrate species. Imidacloprid and thiamethoxam showed equal acute and
chronic toxicity to a winter generation of C. dipterum, whereas thiacloprid was
approximately twice as toxic. The acute and chronic toxicity of imidacloprid was
much higher for the C. dipterum summer generation than for the winter one. The
acute toxicity differs by a factor of 20 for the 96-h 50% effective concentration
(EC50) and by a factor of 5.4 for the chronic 28-d EC50. Temperature had only a
slight effect on the sensitivity of C. dipterum to imidacloprid because we only
found a factor of 1.7 difference in the 96-h EC50 between tests performed at 10
degrees C and 18 degrees C. The difference in sensitivity between summer and
overwintering generations was also found for 3 other insect species. The results
indicate that if the use and environmental fate of the 3 neonicotinoids are
comparable, replacing imidacloprid by another neonicotinoid might not reduce the
environmental impact on the mayfly nymph C. dipterum. The results also show the
importance of reporting which generation is tested because sensitivity values of
insects in the summer might be underestimated by the experiments performed with
neonicotinoids and an overwintering population.
PMID- 26419400
TI - Assignment of Empirical Mode Decomposition Components and Its Application to
Biomedical Signals.
AB - OBJECTIVES: Empirical mode decomposition (EMD) is a frequently used signal
processing approach which adaptively decomposes a signal into a set of narrow
band components known as intrinsic mode functions (IMFs). For multi-trial,
multivariate (multiple simultaneous recordings), and multi-subject analyses the
number and signal properties of the IMFs can deviate from each other between
trials, channels and subjects. A further processing of IMFs, e.g. a simple
ensemble averaging, should determine which IMFs of one signal correspond to IMFs
from another signal. When the signal properties have similar characteristics, the
IMFs are assigned to each other. This problem is known as correspondence problem.
METHODS: From the mathematical point of view, in some cases the correspondence
problem can be transformed into an assignment problem which can be solved e.g. by
the Kuhn-Munkres algorithm (KMA) by which a minimal cost matching can be found.
We use the KMA for solving classic assignment problems, i.e. the pairwise
correspondence between two sets of IMFs of equal cardinalities, and for pairwise
correspondences between two sets of IMFs with different cardinalities
representing an unbalanced assignment problem which is a special case of the k
cardinality assignment problem. RESULTS: A KMA-based approach to solve the
correspondence problem was tested by using simulated, heart rate variability
(HRV), and EEG data. The KMA-based results of HRV decomposition are compared with
those obtained from a hierarchical cluster analysis (state-of-the-art). The major
difference between the two approaches is that there is a more consistent
assignment pattern using KMA. Integrating KMA into complex analysis concepts
enables a comprehensive exploitation of the key advantages of the EMD. This can
be demonstrated by non-linear analysis of HRV-related IMFs and by an EMD-based
cross-frequency coupling analysis of the EEG data. CONCLUSIONS: The successful
application to HRV and EEG analysis demonstrates that our solutions can be used
for automated EMD-based processing concepts for biomedical signals.
PMID- 26419399
TI - Systemic Amyloid A Amyloidosis in Island Foxes (Urocyon littoralis): Severity and
Risk Factors.
AB - Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered
island foxes (Urocyon littoralis) and poses a risk to species recovery. Although
elevated serum AA (SAA) from prolonged or recurrent inflammation predisposes to
AA amyloidosis, additional risk factors are poorly understood. Here we define the
severity of glomerular and medullary renal amyloid and identify risk factors for
AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected
kidneys, amyloid more commonly accumulated in the medullary interstitium than in
the glomeruli (98% [n= 78 of 80] vs 56% [n= 45], respectively;P< .0001), and
medullary deposition was more commonly severe (19% [n= 20 of 105]) as compared
with glomeruli (7% [n= 7];P= .01). Univariate odds ratios (ORs) of severe renal
AA amyloidosis were greater for short- and long-term captive foxes as compared
with free-ranging foxes (ORs = 3.2, 3.7, respectively; overall P= .05) and for
females as compared with males (OR = 2.9;P= .05). Multivariable logistic
regression revealed that independent risk factors for amyloid development were
increasing age class (OR = 3.8;P< .0001), San Clemente Island subspecies versus
San Nicolas Island subspecies (OR = 5.3;P= .0003), captivity (OR = 5.1;P= .0001),
and nephritis (OR = 2.3;P= .01). The increased risk associated with the San
Clemente subspecies or captivity suggests roles for genetic as well as exogenous
risk factors in the development of AA amyloidosis.
PMID- 26419402
TI - DLL4 loss-of-function heterozygous mutations cause Adams-Oliver syndrome.
PMID- 26419401
TI - A longitudinal twin study on Tojikomori and depressive symptoms in Japanese
elderly.
AB - BACKGROUND: Genetic factors associated with Tojikomori (being housebound without
any limitations in physical functioning or mental problems) are unclear. We
performed a twin study to help clarify the causes of Tojikomori and investigate
the association between Tojikomori and depressive symptoms. METHODS: Participants
were members of the Osaka University Aged Twin Registry. A total of 157 twin
pairs (314 individuals) who provided data in 2008 and 2012 were included.
Depressive symptoms were measured by the Geriatric Depression Scale short version
(GDS). Social Activities Scores (SAS) were measured with questions assessing the
frequency of going out and contact with others. Activities of daily living were
assessed with the Barthel index. Structural equation modelling analysis was used
to evaluate the relative importance of genes and environments for the phenotypes
measured. RESULTS: In the first analysis, for SAS (2012), 25% of the variance was
explained by additive genetic effects, and 75% was explained by unique
environmental (including error) effects. For the GDS (2012), 28% of the variance
was explained by additive genetic effects, and 72% was explained by unique
environmental (including error) effects. In the second analysis, 25% of the total
variance in SAS (2012) was explained by additive genetic factors, which
influenced GDS scores (2008 and 2012). However, only 10% of the total variance in
GDS scores (2012) was explained by additive genetic factors that influenced SAS
(2008 and 2012). CONCLUSIONS: Tojikomori was influenced by genetic factors in the
elderly Japanese subjects. The association between Tojikomori and depressive
symptoms was explained by genetic and environmental factors that are common to
both phenotypes. Depressive symptoms were a cause of future Tojikomori and were
affected by additive genetic factors. Genetic factors of Tojikomori were not a
major cause of future depressive symptoms.
PMID- 26419403
TI - Exercise-induced hypoxia secondary to an atrial septal defect and cor triatriatum
dexter.
AB - A 14-year-old boy presented to us with a diagnosis of severe asthma and oxygen
desaturation of 76% on a 6-minute-walk test. A contrast echocardiogram revealed
echocontrast in the left and right atria simultaneously. A secundum atrial septal
defect and partial cor triatriatum dexter were diagnosed, and the atrial defect
was closed by cardiac catheterisation.
PMID- 26419404
TI - Five-day stability of thawed plasma: solvent/detergent-treated plasma comparable
with fresh-frozen plasma and plasma frozen within 24 hours.
AB - BACKGROUND: Plasma stored refrigerated for up to 5 days after thawing is common
practice in many US hospitals. Therefore, clotting factor activities in fresh
frozen plasma (FFP), plasma frozen within 24 hours (PF24), and solvent/detergent
treated plasma (SDP), thawed and stored at 1 to 6 degrees C for up to 5 days,
were investigated. STUDY DESIGN AND METHODS: Five A, B, O, and AB units of FFP,
PF24, and SDP were thawed and maintained for 5 days at 1 to 6 degrees C. The
activity of factor (F)V, FVII, FVIII, protein S (PS), and ADAMTS13 was determined
in each unit at baseline and every 24 hours thereafter for 5 days. RESULTS: After
thaw, mean values of the variables tested were within the normal range in all
three plasma products although, in SDP, FVIII activity was significantly lower (p
= 0.0039). After 5 days of storage all factors significantly declined except for
ADAMTS13 activity, which was stable. Mean FVIII and ADAMTS13 activity was
comparable in all three plasma products and within the normal range, mean FV
activity was significantly lower in FFP and PF24 (p<0.0001) compared to SDP, and
mean FVII activity was significantly lower in PF24 (p<0.03) than in FFP or SDP.
Mean PS activity was below the normal range in all three plasma products with the
lowest values in SDP (p = 0.0001). CONCLUSION: Over 5 days of refrigerated
storage the changes in the measured coagulation factors in FFP, PF24, and SDP are
comparable. Clinical follow-up is needed to assess whether slightly lower PS
levels in SDP are clinically important.
PMID- 26419405
TI - Intrapartum fetal heart rate patterns preceding terminal bradycardia in infants
(>34 weeks) with poor neurological outcome: A regional population-based study in
Japan.
AB - AIM: Intrapartum fetal bradycardia necessitates immediate operative delivery. Our
aim was to investigate the hypothesis that some non-reassuring fetal heart rate
(FHR) patterns were present before the onset of terminal bradycardia in infants
who developed subsequent brain damage. MATERIAL AND METHODS: From a population
based study of 65,197 deliveries, 190 stillbirths, 115 neonatal deaths, and 136
neurologically high-risk infants were registered by the Miyazaki Perinatal
Conference. There were 15 cases of neurologically high-risk infants born at >34
weeks of gestation exhibiting intrapartum terminal bradycardia. Focusing on the
brain-damaged infants, we retrospectively analyzed FHR patterns for at least 1 h
prior to the bradycardia. RESULTS: Brain damage (cerebral palsy [n = 11] and
mental retardation [n = 2]) was diagnosed at 2 years old in 13 out of 15
neurologically high-risk infants. Two infants had bradycardia on admission. In
the remaining 11 infants, FHR patterns were reassuring in six (55%) and non
reassuring in five (45%), including late decelerations (n = 4) and variable
decelerations (n = 2). Clinically relevant factors in the non-reassuring group
included intrauterine infection (n = 3), malpresentation with umbilical cord
coiling (n = 1), and unknown causes (n = 1). Clinically relevant features in the
reassuring group included cord prolapse (n = 1), vaginal breech delivery (n = 1),
shoulder dystocia (n = 1), rupture of membranes (n = 1), and unknown causes (n =
2). CONCLUSION: More than half of the brain-damaged infants born at >34 weeks of
gestation who exhibited intrapartum terminal bradycardia had unremarkable FHR
patterns before abrupt-onset bradycardia. For those with non-reassuring patterns
preceding bradycardia, intrauterine infection was the major sentinel event.
PMID- 26419406
TI - Paenibacillus ripae sp. nov., isolated from bank side soil.
AB - A Gram-stain-variable, rod-shaped, non-motile and endospore-forming bacterium,
designated strain HZ1T, was isolated from a sample of bank side soil from
Hangzhou city, Zhejiang province, PR China. On the basis of 16S rRNA gene
sequence analysis, strain HZ1T was closely related to members of the genus
Paenibacillus, sharing the highest levels of sequence similarity with
Paenibacillus agarexedens DSM 1327T (94.4 %), Paenibacillus sputi KIT00200-70066
1T (94.4 %). Growth occurred at 15-42 degrees C (optimum 30-37 degrees C), pH
5.0-9.5 (optimum pH 7.0-8.0) and NaCl concentrations of up to 6.0 % (w/v) were
tolerated (optimum 0.5 %). The dominant respiratory quinone was MK-7 and the DNA
G+C content was 40.1 mol%. The major fatty acids were anteiso-C15 : 0 and iso-C16
: 0. The major polar lipids of strain HZ1T were diphosphatidylglycerol,
phosphatidylglycerol, phosphatidylethanolamine and several unknown lipids. The
diagnostic diamino acid found in the cell-wall peptidoglycan was meso
diaminopimelic acid. Based on its phenotypic and chemotaxonomic characteristics
and phylogenetic data, strain HZ1T represents a novel species of the genus
Paenibacillus, for which the name Paenibacillus ripae sp. nov. (type strain HZ1T
= CCTCC AB 2014276T = LMG 28639T) is proposed.
PMID- 26419407
TI - Cleft palate in a patient with the nested 22q11.2 LCR C to D deletion.
PMID- 26419408
TI - Lipid droplet distribution of immature canine oocytes in relation to their size
and the reproductive stage.
AB - This study investigated the distribution of lipid droplets (LD) in immature
canine oocytes in relation to their size and the reproductive stage. Oocytes were
collected from the ovaries of bitches at different estrous stages, divided
according to their size (110-120 um; >120 um), and stained with Nile Red to
detect lipid droplet distribution. At the follicular phase most of the oocytes
displayed a diffuse pattern of LD distribution, whereas at anestrus and luteal
phase oocytes showed LD mainly in a peripheral/ perinuclear LD distribution. A
significantly higher intensity of LD has been recorded in the oocytes > 120 um
compared to those of smaller size (110 - 120 um) at all stages of the estrous
cycle. At follicular phase, oocytes > 120 um displayed LD intensity similar to
that of oocytes > 120 um at luteal phase and higher compared to the oocytes of
the other groups.
PMID- 26419409
TI - Physical assessment techniques performed by Italian registered nurses: a
quantitative survey.
AB - AIMS AND OBJECTIVES: The aims of the study were to describe which of the core
techniques of the physical assessment are regularly performed by a sample of
Italian nurses, and to investigate the potential predictors of a more complete
examination. BACKGROUND: Physical examination is among the essential tasks of
nursing professionals, who are requested to perform a correct and complete
physical assessment. DESIGN: Cross-sectional survey. METHODS: The study was
performed between August 2013 and January 2014 in 17 Italian regions. A total of
1182 questionnaires were collected. RESULTS: Most participants were females (age
range 41-50 years), and worked in Internal Medicine, Intensive Care and Surgical
hospital units. Of the 30 core techniques that are currently taught and performed
according to the Italian Baccalaureate degree requirements, 20 were routinely
performed, 6 were seldom used and 4 were learnt but almost never performed
(auscultation of lung, heart and bowel sounds and spine inspection). Graduate and
postgraduate nurses, working in Intensive Care Units and Nursing Homes, were more
prone than the others to carry out a more complete physical assessment.
CONCLUSIONS: The skills to perform a physical assessment are suboptimal among
this sample of Italian nurses. Health and educational providers should pose more
attention and efforts to provide nurses with an acceptable training in physical
examination practice. RELEVANCE TO CLINICAL PRACTICE: This study describes the
specific physical techniques performed by nurses in real practice and provides
information on which skills require more attention in nursing educational
programmes.
PMID- 26419410
TI - Metabolic changes in rat urine after acute paraquat poisoning and discriminated
by support vector machine.
AB - Paraquat is quick-acting and non-selective, killing green plant tissue on
contact; it is also toxic to human beings and animals. In this study, we
developed a urine metabonomic method by gas chromatography-mass spectrometry to
evaluate the effect of acute paraquat poisoning on rats. Pattern recognition
analysis, including both partial least squares discriminate analysis and
principal component analysis revealed that acute paraquat poisoning induced
metabolic perturbations. Compared with the control group, the levels of
benzeneacetic acid and hexadecanoic acid of the acute paraquat poisoning group
(intragastric administration 36 mg/kg) increased, while the levels of butanedioic
acid, pentanedioic acid, altronic acid decreased. Based on these urinary
metabolomics data, support vector machine was applied to discriminate the
metabolomic change of paraquat groups from the control group, which achieved 100%
classification accuracy. In conclusion, metabonomic method combined with support
vector machine can be used as a useful diagnostic tool in paraquat-poisoned rats.
PMID- 26419411
TI - Evaluating the treatment effects model for estimation of cross-sectional
associations between risk factors and cardiovascular biomarkers influenced by
medication use.
AB - PURPOSE: In cross-sectional observational data, evaluation of biomarker-to
exposure associations is often complicated by nonrandom medication use.
Traditional approaches often lead to biased estimates, consistent with known
results involving confounding by indication. More sophisticated, yet easy to
implement approaches such as inverse probability weighting and censored normal
regression can address medication use in certain settings but have poor
performance when medication use depends on off-medication biomarker values. More
sophisticated approaches are necessary. METHODS: Heckman's treatment effects
model resembles the process that gives rise to cross-sectional data. In this
study, we conduct a variety of simulation studies to illustrate why traditional
approaches are inappropriate when medication use depends on underlying biomarker
values. We illustrate how Heckman's model can accommodate this feature. We also
apply the models to data from the Multi-Ethnic Study of Atherosclerosis. RESULTS:
Inverse probability weighting and censored normal regression are sensitive to how
strongly medication use is associated with untreated biomarker values (the
untreated value acts as an unmeasured predictor of medication use in this
context). Heckman's model can often adequately remove bias and is robust to
certain forms of model misspecification but relies on knowing important
predictors of medication use, even when they are independent of the biomarker.
The advantages of Heckman's model can be negated if the effect of medication on
biomarker values is proportionate to the underlying biomarker. CONCLUSIONS: If
predictors of medication use are measured, data are cross-sectional, and effects
are approximately additive, then Heckman's model is more accurate relative to
alternative approaches.
PMID- 26419413
TI - 25 MHz clock continuous-variable quantum key distribution system over 50 km fiber
channel.
AB - In this paper, a practical continuous-variable quantum key distribution system is
developed and it runs in the real-world conditions with 25 MHz clock rate. To
reach high-rate, we have employed a homodyne detector with maximal bandwidth to
300 MHz and an optimal high-efficiency error reconciliation algorithm with
processing speed up to 25 Mbps. To optimize the stability of the system, several
key techniques are developed, which include a novel phase compensation algorithm,
a polarization feedback algorithm, and related stability method on the
modulators. Practically, our system is tested for more than 12 hours with a final
secret key rate of 52 kbps over 50 km transmission distance, which is the highest
rate so far in such distance. Our system may pave the road for practical
broadband secure quantum communication with continuous variables in the
commercial conditions.
PMID- 26419414
TI - Non-antibiotic 12-membered macrolides: design, synthesis and biological
evaluation in a cigarette-smoking model.
AB - The 14-membered macrolide erythromycin A expresses three distinct biological
properties, including antibacterial activity, gastrointestinal motor-stimulating
activity and anti-inflammatory and/or immunomodulatory effects. Although low
dose, long-term therapy using 14- and 15-membered macrolides displaying anti
inflammatory and/or immunomodulatory activity effectively treats diffuse
panbronchiolitis and chronic sinusitis, bacterial resistance may emerge. To
address this issue, we developed the 12-membered non-antibiotic macrolide (8R,9S)
8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900) that promotes
monocyte to macrophage differentiation, a marker for anti-inflammatory and/or
immunomodulatory effects, without possessing antibacterial activity. In this
article, we report that the new macrolide derivative (8R,9S) -de(3'-N-methyl)-3'
N-(p-chlorobenzyl)-de(3-O-cladinosyl)-3-dehydro-8,9-dihydro-6,9-epoxy-8,9
anhydropseudoerythromycin A 12,13-carbonate (EM939) exhibited stronger promotive
activity for monocyte to macrophage differentiation than that of the parent
compound EM900 in addition to reduced cytotoxicity toward THP-1 cells and
antibacterial inactivity. In a cigarette-smoking model used to simulate chronic
obstructive pulmonary disease (COPD), the EM900 derivatives significantly
attenuated lung and alveolar inflations, functionally and histologically, via
oral administration. Because of these marked therapeutic effects, non-antibiotic
EM900 derivatives may become central to the treatment of chronic inflammatory
diseases such as COPD.
PMID- 26419415
TI - Increased resistance rate to ceftazidime among blood culture isolates of ESBL
producing Escherichia coli in a university-affiliated hospital of China.
PMID- 26419416
TI - High population densities of Macrolophus pygmaeus on tomato plants can cause
economic fruit damage: interaction with Pepino mosaic virus?
AB - BACKGROUND: The zoophytophagous predator Macrolophus pygmaeus Rambur (Hemiptera:
Miridae) is a successful biocontrol agent against several pest species in
protected tomato crops. This predator is considered to be harmless for the crop.
However, in recent years, Heteroptera feeding punctures on tomato fruit in
Belgian and Dutch greenhouses have been misinterpreted as Pepino mosaic virus
(PepMV) symptoms. In this study, three hypotheses were tested: (1) M. pygmaeus
causes fruit damage that increases with population density and surpasses economic
thresholds; (2) the presence of prey or alternative prey reduces the damage; (3)
an infection of the tomato plants by PepMV triggers or aggravates M. pygmaeus
fruit damage. RESULTS: At increasing M. pygmaeus densities, the severity of fruit
damage increased from a few dimples towards yellowish discoloration and deformed
fruits. A correlation with an infection with PepMV was found. The severity of the
symptoms was independent of the presence of prey. A minimum economic density
threshold was estimated at 0.32 M. pygmaeus per leaf. CONCLUSION: M. pygmaeus can
cause economic damage to tomato fruits at densities common in practice. An
infection of the plants with PepMV enhances fruit symptoms significantly.
Interacting plant defence responses are most likely the key to explaining this,
although confirmation is required. (c) 2015 Society of Chemical Industry.
PMID- 26419417
TI - Logical error rate in the Pauli twirling approximation.
AB - The performance of error correction protocols are necessary for understanding the
operation of potential quantum computers, but this requires physical error models
that can be simulated efficiently with classical computers. The Gottesmann-Knill
theorem guarantees a class of such error models. Of these, one of the simplest is
the Pauli twirling approximation (PTA), which is obtained by twirling an
arbitrary completely positive error channel over the Pauli basis, resulting in a
Pauli channel. In this work, we test the PTA's accuracy at predicting the logical
error rate by simulating the 5-qubit code using a 9-qubit circuit with realistic
decoherence and unitary gate errors. We find evidence for good agreement with
exact simulation, with the PTA overestimating the logical error rate by a factor
of 2 to 3. Our results suggest that the PTA is a reliable predictor of the
logical error rate, at least for low-distance codes.
PMID- 26419419
TI - Bandgap- and Radial-Position-Dependent Mn-Doped Zn-Cu-In-S/ZnS Core/Shell
Nanocrystals.
AB - This paper presents a mechanistic study on the doping of Zn-Cu-In-S/ZnS
core/shell quantum dots (QDs) with Mn by changing the Zn-Cu-In-S QD bandgap and
dopant position inside the samples (Zn-Cu-In-S core and ZnS shell). Results show
that for the Mn:Zn-Cu-In-S/ZnS system, a Mn-doped emission can be obtained when
the bandgap value of the QDs is larger than the energy of Mn-doped emission.
Conversely, a bandgap emission is only observed for the doped system when the
bandgap value of QDs is smaller than the energy gap of the Mn-doped emission. In
the Zn-Cu-In-S/Mn:ZnS systems, doped QDs show dual emissions, consisting of
bandgap and Mn dopant emissions, instead of one emission band when the value of
the host bandgap is larger than the energy of the Mn-doped emission. These
findings indicate that the emission from Mn-doped Zn-Cu-In-S/ZnS core/shell QDs
depends on the bandgap of the QDs and the dopant position inside the core/shell
material. The critical bandgap of the host materials is estimated to have the
same value as the energy of the Mn d-d transition. Subsequently, the mechanism of
photoluminescence properties of the Mn:Zn-Cu-In-S/ZnS and Zn-Cu-In-S/Mn:ZnS
core/shell QD systems is proposed. Control experiments are then carried out by
preparing Mn-doped Zn(Cu)-In-S QDs with various bandgaps, and the results confirm
the reliability of the suggested mechanism. Therefore, the proposed mechanism can
aid the design and synthesis of novel host materials in fabricating doped QDs.
PMID- 26419418
TI - Cognitive tutoring induces widespread neuroplasticity and remediates brain
function in children with mathematical learning disabilities.
AB - Competency with numbers is essential in today's society; yet, up to 20% of
children exhibit moderate to severe mathematical learning disabilities (MLD).
Behavioural intervention can be effective, but the neurobiological mechanisms
underlying successful intervention are unknown. Here we demonstrate that eight
weeks of 1:1 cognitive tutoring not only remediates poor performance in children
with MLD, but also induces widespread changes in brain activity. Neuroplasticity
manifests as normalization of aberrant functional responses in a distributed
network of parietal, prefrontal and ventral temporal-occipital areas that support
successful numerical problem solving, and is correlated with performance gains.
Remarkably, machine learning algorithms show that brain activity patterns in
children with MLD are significantly discriminable from neurotypical peers before,
but not after, tutoring, suggesting that behavioural gains are not due to
compensatory mechanisms. Our study identifies functional brain mechanisms
underlying effective intervention in children with MLD and provides novel metrics
for assessing response to intervention.
PMID- 26419420
TI - Dynamic scaling for the growth of non-equilibrium fluctuations during
thermophoretic diffusion in microgravity.
AB - Diffusion processes are widespread in biological and chemical systems, where they
play a fundamental role in the exchange of substances at the cellular level and
in determining the rate of chemical reactions. Recently, the classical picture
that portrays diffusion as random uncorrelated motion of molecules has been
revised, when it was shown that giant non-equilibrium fluctuations develop during
diffusion processes. Under microgravity conditions and at steady-state, non
equilibrium fluctuations exhibit scale invariance and their size is only limited
by the boundaries of the system. In this work, we investigate the onset of non
equilibrium concentration fluctuations induced by thermophoretic diffusion in
microgravity, a regime not accessible to analytical calculations but of great
relevance for the understanding of several natural and technological processes. A
combination of state of the art simulations and experiments allows us to attain a
fully quantitative description of the development of fluctuations during
transient diffusion in microgravity. Both experiments and simulations show that
during the onset the fluctuations exhibit scale invariance at large wave vectors.
In a broader range of wave vectors simulations predict a spinodal-like growth of
fluctuations, where the amplitude and length-scale of the dominant mode are
determined by the thickness of the diffuse layer.
PMID- 26419421
TI - Isolation and Crystallographic Characterization of Gd3N@D2(35)-C88 through Non
Chromatographic Methods.
AB - While several nonchromatographic methods are available for the isolation and
purification of endohedral fullerenes of the type M3N@Ih-C80, little work has
been done that would allow other members of the M3N@C2n family to be isolated
with minimal chromatography. Here, we report that Gd3N@D2(35)-C88 can be isolated
from the multitude of endohedral and empty cage fullerenes present in carbon soot
obtained by electric-arc synthesis using Gd2O3-doped graphite rods. The procedure
developed utilizes successive precipitation with the Lewis acids CaCl2 and ZnCl2
followed by treatment with amino-functionalized silica gel. The structure of the
product was identified by single-crystal X-ray diffraction.
PMID- 26419423
TI - Leadership by example: saying no to health industry board membership.
PMID- 26419422
TI - Structure-Affinity Relationship Analysis of Selective FKBP51 Ligands.
AB - The FK506-binding protein 51 (FKBP51) is a promising drug target for the
treatment of stress-related psychiatric or metabolic disorders. Just recently,
the first selective ligands for FKBP51 were reported based on an induced fit
mechanism, but they are too large for a further drug development process. We
therefore designed and synthesized a novel series of selective ligands to explore
the requirements necessary for binding to the induced-fit conformation. All
ligands of this series show no binding toward the structurally very similar
antitarget FKBP52. With the cocrystal structure of the best ligand in this novel
series we confirmed the induced fit mechanism. Furthermore, the structure
affinity relationship provides information about beneficial structural features,
which is valuable for the development of improved FKBP51-directed drugs.
PMID- 26419424
TI - Copper-catalyzed electrophilic amination of sodium sulfinates at room
temperature.
AB - By using O-benzoyl hydroxylamines as amine sources, the first convenient copper
catalyzed electrophilic amination of sodium sulfinates has been realized. Even
with 2 mol% catalyst loading, the protocol provided an efficient and
straightforward synthesis of a broad range of functional sulfonamides under
ambient reaction conditions without an additional base and ligand. Based on the
control experiments, a plausible mechanism was proposed.
PMID- 26419425
TI - SAMSVM: A tool for misalignment filtration of SAM-format sequences with support
vector machine.
AB - Sequence alignment/map (SAM) formatted sequences [Li H, Handsaker B, Wysoker A et
al., Bioinformatics 25(16):2078-2079, 2009.] have taken on a main role in
bioinformatics since the development of massive parallel sequencing. However,
because misalignment of sequences poses a significant problem in analysis of
sequencing data that could lead to false positives in variant calling, the
exclusion of misaligned reads is a necessity in analysis. In this regard, the
multiple features of SAM-formatted sequences can be treated as vectors in a multi
dimension space to allow the application of a support vector machine (SVM).
Applying the LIBSVM tools developed by Chang and Lin [Chang C-C, Lin C-J, ACM
Trans Intell Syst Technol 2:1-27, 2011.] as a simple interface for support vector
classification, the SAMSVM package has been developed in this study to enable
misalignment filtration of SAM-formatted sequences. Cross-validation between two
simulated datasets processed with SAMSVM yielded accuracies that ranged from 0.89
to 0.97 with F-scores ranging from 0.77 to 0.94 in 14 groups characterized by
different mutation rates from 0.001 to 0.1, indicating that the model built using
SAMSVM was accurate in misalignment detection. Application of SAMSVM to actual
sequencing data resulted in filtration of misaligned reads and correction of
variant calling.
PMID- 26419426
TI - A new chiral uranyl phosphonate framework consisting of achiral building units
generated from ionothermal reaction: structure and spectroscopy
characterizations.
AB - The ionothermal reactions of uranyl nitrate and 1,3-pbpH4 (1,3-pbpH4 = 1,3
phenylenebis(phosphonic acid) ligand in ionic liquids of [C4mim][Dbp],
[C4mpyr][Br], and [Etpy][Br], respectively, afforded three new uranyl
phosphonates, namely [C4mim][(UO2)2(1,3-pbpH)(1,3-pbpH).Hmim] (1), [UO2(1,3
pbpH2)H2O.mpr] (2), and [Etpy][UO2(1,3-pbpH2)F] (3). Compound 1 exhibits a rare
example of a chiral uranyl phosphonate 3D framework structure built from achiral
building units of tetragonal bipyramidal uranium polyhedra and 1,3-pbp ligands.
The structure adopts a network with channels extending along the b axis, which
are filled with C4mim(+) and protonated 1-methylimidazole. In sharp contrast,
compounds 2 & 3 both show pillared topology composed of uranyl pentagonal
bipyramid polyhedra and phosphonate ligands. The layers are neutral in compound 2
with N-methylpyrrole molecules in the interlayer space, while compound 3 adopts
anionic layer, and the charge is compensated with N-ethyl-pyridinium cations
between the layers. Although compounds 1, 2, and 3 were synthesized under
identical conditions with sole variation of the ionic liquid species, the
resulting structures show a rich diversity in the local coordination environment
of uranyl ions, the protonation of the phosphonate ligand, the conformation of
ionic liquid ions, and the overall arrangement of the structure. All compounds
were characterized by absorption, temperature dependent fluorescence, as well as
infrared and Raman spectroscopies.
PMID- 26419427
TI - Role of Locoregional Therapy and Predictors for Dropout in Patients with
Hepatocellular Carcinoma Listed for Liver Transplantation.
AB - PURPOSE: To identify factors associated with removal from the liver
transplantation waitlist because of death, deterioration of condition, or
exceeding Milan criteria in patients with hepatocellular carcinoma (HCC), with
emphasis on the role of locoregional therapy (LRT), defined as percutaneous
thermal ablation and drug-eluting embolic chemoembolization, as bridge therapy.
MATERIALS AND METHODS: All patients listed for liver transplant at a single
institution with exception points for HCC during 2004-2012 were evaluated. The
most common cause of cirrhosis was hepatitis C (68%; 121/177). Seventy-one
percent (125/177) of patients underwent liver transplantation, and 83% (147/177)
underwent at least 1 LRT procedure. Of the 52 patients who did not undergo liver
transplantation, 31 (60%) of livers were removed because of progression of HCC.
RESULTS: The likelihood of transplant was higher for patients who received LRT
(odds ratio [OR], 2.9; confidence interval [CI], 2.2-7.2) and lower for patients
with multifocal tumors (OR, 0.25; CI, 0.12-0.52) and with larger tumors (OR,
0.94; CI, 0.90-0.98). Time on the waitlist (OR, 0.99; CI, 0.99-1.0) was not found
to correlate with removal. LRT increased the likelihood of liver transplantation,
specifically for patients with prolonged wait times. Patients who demonstrated
complete response (CR) to LRT on the first follow-up imaging study were more
likely to undergo liver transplantation. CONCLUSIONS: LRT increased the
likelihood of a patient with HCC achieving liver transplant, particularly in
patients facing prolonged waiting times. CR after LRT significantly increased the
likelihood of liver transplantation.
PMID- 26419428
TI - Transdermal delivery of biopharmaceuticals: dream or reality?
AB - The skin being the largest organ of the body presents a potential route for
administration of drugs. Passive transdermal products such as gels, creams and
patches deliver drugs effectively across the skin. However, this approach is
limited to lipophilic molecules with low molecular weights. Passive transdermal
delivery of proteins and peptides which are hydrophilic with high molecular
weights is negligible. This led to the development of various ways of surmounting
the skin barrier so as to make this route feasible for peptide and protein
delivery. The current article reviews various active transdermal technologies
with special emphasis on microneedle mediated delivery. Microneedles, especially
dissolvable microneedles present an excellent platform for protein and peptide
delivery. Significant advances have been made in the past decade in this area.
Published literature shows a broad spectrum of molecules being delivered
successfully via microneedles. However, success in clinic will give a boost to
all the efforts and advances made in this field so far.
PMID- 26419429
TI - Is audit the answer? Formally including research and audit in emergency medicine
practice better equips us for future clinical and political challenges.
PMID- 26419430
TI - A crossbred reference population can improve the response to genomic selection
for crossbred performance.
AB - BACKGROUND: Breeding goals in a crossbreeding system should be defined at the
commercial crossbred level. However, selection is often performed to improve
purebred performance. A genomic selection (GS) model that includes dominance
effects can be used to select purebreds for crossbred performance. Optimization
of the GS model raises the question of whether marker effects should be estimated
from data on the pure lines or crossbreds. Therefore, the first objective of this
study was to compare response to selection of crossbreds by simulating a two-way
crossbreeding program with either a purebred or a crossbred training population.
We assumed a trait of interest that was controlled by loci with additive and
dominance effects. Animals were selected on estimated breeding values for
crossbred performance. There was no genotype by environment interaction. Linkage
phase and strength of linkage disequilibrium between quantitative trait loci
(QTL) and single nucleotide polymorphisms (SNPs) can differ between breeds, which
causes apparent effects of SNPs to be line-dependent. Thus, our second objective
was to compare response to GS based on crossbred phenotypes when the line origin
of alleles was taken into account or not in the estimation of breeding values.
RESULTS: Training on crossbred animals yielded a larger response to selection in
crossbred offspring compared to training on both pure lines separately or on both
pure lines combined into a single reference population. Response to selection in
crossbreds was larger if both phenotypes and genotypes were collected on
crossbreds than if phenotypes were only recorded on crossbreds and genotypes on
their parents. If both parental lines were distantly related, tracing the line
origin of alleles improved genomic prediction, whereas if both parental lines
were closely related and the reference population was small, it was better to
ignore the line origin of alleles. CONCLUSIONS: Response to selection in
crossbreeding programs can be increased by training on crossbred genotypes and
phenotypes. Moreover, if the reference population is sufficiently large and both
pure lines are not very closely related, tracing the line origin of alleles in
crossbreds improves genomic prediction.
PMID- 26419431
TI - Caffeine's influence on object recognition and working-memory in prepubertal mice
and its modulation by gender.
AB - OBJECTIVE: This study investigated the effects of intraperitoneal injection of
caffeine on Y-maze working-memory and novel object recognition (NOR) in
prepubertal mice. METHODOLOGY: Y-maze spontaneous alternation and a novel object
recognition test (consisting of acclimation, acquisition and test phases) were
performed. Mice received a single dose of caffeine (10, 20, 40, 80 and 120mgkg(
1) i.p.) or vehicle, 30min before Y-maze exploration. For the NOR test, caffeine
was given 30min before training and another dose 30min before test phase.
RESULTS: NOR time (acquisition phase) increased significantly in males at all
doses of caffeine and decreased in females at 10, 20 and 40mg/kg compared to
vehicle; during the test phase, novel object exploration time decreased
significantly in males and increased in females at 10 and 20mg/kg only to
decrease again at 120mg/kg. Recognition index decreased in males and increased in
females while, males showed poor discrimination between novel and familiar
objects compared to vehicle; while females showed increased discrimination
between novel and familiar object at 10, 20,40 and 80mg/kg and a decrease at
120mg/kg. Y-maze spontaneous alternation improved significantly in males at 10
and 40mg/kg and decreased at 20 and 120mg/kg in females. CONCLUSION: The findings
suggest that acute caffeine injection improves non-spatial memory retention in
female mice but not in males; spatial working-memory is however improved in males
but not in females.
PMID- 26419432
TI - A 26-hour system of highly sensitive whole genome sequencing for emergency
management of genetic diseases.
AB - While the cost of whole genome sequencing (WGS) is approaching the realm of
routine medical tests, it remains too tardy to help guide the management of many
acute medical conditions. Rapid WGS is imperative in light of growing evidence of
its utility in acute care, such as in diagnosis of genetic diseases in very ill
infants, and genotype-guided choice of chemotherapy at cancer relapse. In such
situations, delayed, empiric, or phenotype-based clinical decisions may meet with
substantial morbidity or mortality. We previously described a rapid WGS method,
STATseq, with a sensitivity of >96 % for nucleotide variants that allowed a
provisional diagnosis of a genetic disease in 50 h. Here improvements in
sequencing run time, read alignment, and variant calling are described that
enable 26-h time to provisional molecular diagnosis with >99.5 % sensitivity and
specificity of genotypes. STATseq appears to be an appropriate strategy for
acutely ill patients with potentially actionable genetic diseases.
PMID- 26419434
TI - Strategies to implement evidence into practice to improve palliative care:
recommendations of a nominal group approach with expert opinion leaders.
AB - BACKGROUND: In the past decades, many new insights and best practices in
palliative care, a relatively new field in health care, have been published.
However, this knowledge is often not implemented. The aim of this study therefore
was to identify strategies to implement improvement activities identified in a
research project within daily palliative care practice. METHODS: A nominal group
technique was used with members of the IMPACT consortium, being international
researchers and clinicians in cancer care, dementia care and palliative care.
Participants identified and prioritized implementation strategies. Data was
analyzed qualitatively using inductive coding. RESULTS: Twenty international
clinicians and researchers participated in one of two parallel nominal group
sessions. The recommended strategies to implement results from a research project
were grouped in five common themes: 1. Dissemination of results e.g. by
publishing results tailored to relevant audiences, 2. Identification and
dissemination of unique selling points, 3. education e.g. by developing e
learning tools and integrating scientific evidence into core curricula, 4.
Stimulation of participation of stakeholders, and 5. consideration of
consequences e.g. rewarding services for their implementation successes but not
services that fail to implement quality improvement activities. DISCUSSION: The
added value of this nominal group study lies in the prioritisation by the experts
of strategies to influence the implementation of quality improvement activities
in palliative care. Efforts to ensure future use of scientific findings should be
built into research projects in order to prevent waste of resources.
PMID- 26419433
TI - Impact of long-term steroid therapy on epicardial and pericardial fat deposition:
a cardiac MRI study.
AB - BACKGROUND: Increased cardiac fat has been identified as a risk factor for
coronary artery disease. Metabolic syndrome is associated with increased cardiac
fat deposition. Steroids are known to imitate some effects of metabolic syndrome
and are frequently used in patients with rheumatic disorders. Primary aim was to
evaluate the impact of long-term steroid use on cardiac fat deposition in
patients with rheumatic disorders. In addition, we sought to investigate if this
effect might be dose-dependent. METHODS: Patients were enrolled as follows: (1)
rheumatic disorder; and (2) long-term steroid therapy, and (3) underwent
cardiovascular magnetic resonance (CMR) imaging. Patients were stratified in a
high-dose (>7.5 mg prednisone equivalent/day for at least 6 months) and a low
dose steroid group (<7.5 mg prednisone equivalent/day) and compared to steroid
naive controls without rheumatic disorders. RESULTS: 122 patients were included
(n = 61 steroid patients, n = 61 controls). N = 36 were classified as high-dose,
n = 25 as low-dose steroid group. Steroid patients showed larger epicardial 5.7
[3.5-9.1] cm(2) and pericardial 13.0 [6.1-26.8] cm(2) areas of fat than controls
4.2 [1.3-5.8] cm(2)/6.4 [1.6-15.4] cm(2), p < 0.001, p < 0.01, respectively. High
dose steroid patients had more epi- and pericardial fat both than controls: 7.2
[4.2-11.1] cm(2) vs. 4.4 [1.0-6.0] cm(2), p < 0.001; 18.6 [8.9-38.2] cm(2) vs.
10.7 [4.7-26.8] cm(2), p < 0.05, and patients in the low-dose steroid group (p <
0.01, p < 0.001, respectively). CONCLUSION: The present data suggest increased
cardiac fat deposition in steroid-treated patients with rheumatic disorders.
Furthermore, this accumulation of cardiac fat seems to be dose-dependent,
pointing towards a cumulative effect of steroids.
PMID- 26419435
TI - Isolation and characterization of twelve polymorphic microsatellite loci for
Hypochaeris catharinensis (Asteraceae) and cross-amplification in related
species.
PMID- 26419436
TI - Development and characterization of eighty-one microsatellite markers in Indian
white shrimp, Fenneropenaeus indicus, through cross-amplification.
PMID- 26419437
TI - Identification of novel insertion-deletion markers for Dongxiang wild rice (Oryza
rufipogon Griff.) using high-throughput sequencing technology.
PMID- 26419439
TI - Understanding and safeguarding patient dignity in intensive care.
AB - BACKGROUND: Dignity has been highlighted in previous research as one of the most
important ethical concerns in nursing care. According to Eriksson, dignified
caring is related to treating the patient as a unique human being and respecting
human value. Intensive care unit patients are vulnerable to threatened dignity,
and maintaining dignity may be challenging as a consequence of critical illness.
OBJECTIVES: The aim is to highlight how nurses in an intensive care setting
understand patient dignity, what threatens patient dignity and how nurses can
safeguard patient dignity. Research design and participants: Data materials were
collected through a survey questionnaire which contained open questions about
patient dignity, and the text was analysed using hermeneutic reading and text
interpretation. Totally, 25 nurses employed in an intensive care unit in Finland
participated in the study. Ethical considerations: The study follows the
guidelines for good scientific practice by the Finnish Advisory Board on Research
Integrity and the ethical principles according to the Declaration of Helsinki.
FINDINGS: Findings revealed that nurses recognize the patients' absolute dignity
by regarding them as unique human beings. The nurses also recognize the
importance of shared humanity in preserving patient dignity. Intensive care
patients' dignity is threatened by negative attitudes and when their integrity is
not being protected. Dignity is also threatened when patients and nurses are not
part of the patients' care and patient care decisions, when patients receive care
against their will and because of the acute nature of intensive care.
PMID- 26419438
TI - Moral sensitivity and moral distress in Iranian critical care nurses.
AB - BACKGROUND: Moral sensitivity is the foremost prerequisite to ethical
performance; a review of literature shows that nurses are sometimes not sensitive
enough for a variety of reasons. Moral distress is a frequent phenomenon in
nursing, which may result in paradoxes in care, dealing with patients and
rendering high-quality care. This may, in turn, hinder the meeting of care
objectives, thus affecting social healthcare standards. RESEARCH OBJECTIVE: The
present research was conducted to determine the relationship between moral
sensitivity and moral distress of nurses in intensive care units. RESEARCH
DESIGN: This study is a descriptive-correlation research. Lutzen's moral
sensitivity questionnaire and Corley Moral Distress Questionnaire were used to
gather data. Participants and research context: A total of 153 qualified nurses
working in the hospitals affiliated to Shahid Beheshti University of Medical
Sciences were selected for this study. Subjects were selected by census method.
Ethical considerations: After explaining the objectives of the study, all the
participants completed and signed the written consent form. To conduct the study,
permission was obtained from the selected hospitals. FINDINGS: Nurses' average
moral sensitivity grade was 68.6 +/- 7.8, which shows a moderate level of moral
sensitivity. On the other hand, nurses also experienced a moderate level of moral
distress (44.8 +/- 16.6). Moreover, there was no meaningful statistical
relationship between moral sensitivity and moral distress (p = 0.26). DISCUSSION:
Although the nurses' moral sensitivity and moral distress were expected to be
high in the intensive care units, it was moderate. This finding is consistent
with the results of some studies and contradicts with others. CONCLUSION: As
moral sensitivity is a crucial factor in care, it is suggested that necessary
training be provided to develop moral sensitivity in nurses in education and
practical environments. Furthermore, removing factors that contribute to moral
distress may help decrease it in nurses.
PMID- 26419440
TI - A Radiation Oncologist's Guide to Contouring the Lacrimal Gland.
PMID- 26419441
TI - Dental amalgam artifact: Adverse impact on tumor visualization and proton beam
treatment planning in oral and oropharyngeal cancers.
AB - PURPOSE: We evaluated the incidence and impact of dental filling artifacts on the
definition of clinical target volume (CTV) for oropharyngeal/oral cavity cancers
receiving radiation therapy. We performed phantom proton beam dosimetric analyses
using a low-density composite filling to investigate artifact reduction and dose
distribution. METHODS AND MATERIALS: We reviewed oral cavity/oropharynx radiation
treatment plans between 2010 and 2012. Plans were evaluated for artifacts and
impact on CTV visualization. We constructed a head and neck phantom, obtaining
planning computed tomography images at baseline (native tooth) and for each
filling (composite and metal amalgam) interchanged into a tooth adjacent to the
tumor. We performed uniform scanning proton plans with each filling, evaluating
for planning target volume (PTV) coverage and overall dose distribution. RESULTS:
A total of 110 treatment plans were reviewed (71 oropharynx, 39 oral cavity).
Artifacts were identified in 81 plans (73.6%), including 53 oropharynx (74.6%)
and 28 oral cavity (71.8%). Artifacts obscured the CTV in 77 cases (95%),
including 49 of 53 oropharynx cases (92.5%) and all 28 oral cavity cases. On
phantom testing, the metal amalgam obscured the tumor while the composite did
not. Hounsfield unit (HU) values (range, mean) for the tumor were: baseline (
484.0 to 700.0 HU, 104 HU), composite (-728.5 to 1038.0 HU, 105 HU), metal
amalgam (-1023.0 to 807.0 HU, 90.74 HU). The percent of planning target volume
receiving 95% of prescription dose of the PTV was baseline (100%), composite
(100%), and metal amalgam (92.3%). PTV dose ranges were baseline (98%-106%),
composite (98%-107%), and metal amalgam (66%-111%). PTV coverage and dose
distributions of the composite and native tooth plans were identical.
CONCLUSIONS: A high incidence of artifacts was found on the planning scans of
oral/oropharyngeal cancer patients, adversely impacting CTV visualization. In our
phantom model, metal amalgam impacted tumor and tissue density. The PTV was
underdosed with the metal amalgam compared with the composite filling. A
potential solution involves exchanging metal fillings with composite before
proton treatment planning for improved tumor visualization and dosimetry.
PMID- 26419442
TI - Results of the 2014 Survey of the Association of Directors of Radiation Oncology
Programs (ADROP).
AB - BACKGROUND: In 2014, the Association of Directors of Radiation Oncology Programs
(ADROP) conducted an in-depth survey of program directors along several axes. We
report the results of this survey and compare the major findings with those of
the 2007 ADROP survey. METHODS AND MATERIALS: The survey was written and approved
by ADROP leadership in 2012, announced online through broadcasts throughout 2013
and early 2014, and closed in mid-2014. The results based on question groups
related to (1) hours spent in activities, (2) budget and nonprogram resources,
(3) physics/biology didactics, (4) mock exams/didactics/research, (5) electives,
(6) students, and (7) resources/challenges were tabulated. Descriptive
comparisons with the 2007 survey were performed. RESULTS: There was 26%
participation (23/88 programs). Major areas of time commitment were faculty and
site organization, maintenance, and corrections (70 hours/year) and
didactics/conferences and rounds (200 hours/year). The median program director
protected time was 23% (range 0%-50%). All responding programs (100%) had biology
and physics courses and assigned directors, but only approximately 20% of
respondents had a threshold grade in these courses for graduation. Major
resources desired were templates of goals/objectives by disease site, competency
evaluations by level, journal club repository, and software for contouring, oral
examination preparation, grant writing, publication writing, oral presentation,
and effective teaching. Major activity challenges were Accreditation Council for
Graduate Medical Education external review and time commitment. CONCLUSIONS:
Overall, the 2014 results are similar to those of the 2007 survey. The average
time commitment remains considerably higher than the 10% minimum required in the
current ACGME program requirements. The survey results may guide ADROP membership
in centralizing some of the identified resources needed.
PMID- 26419443
TI - Dosimetric effect of photon beam energy on volumetric modulated arc therapy
treatment plan quality due to body habitus in advanced prostate cancer.
AB - PURPOSE: The purpose of this study was to dosimetrically compare 6- and 10-MV
photon beam energies in high-risk prostate cancer patients of various body
habitus using a volumetric modulated arc therapy (VMAT) radiation delivery
technique. The objectives of the study were to evaluate whether dosimetric
differences exist and to investigate whether differences are dependent on patient
body habitus. METHODS AND MATERIALS: Forty patients with various body habitus who
had previously received treatment to the prostate and pelvic lymph nodes with
VMAT techniques were chosen. Patients were planned in the Pinnacle(3) treatment
planning system with double or triple SmartArc plans with 6- and 10-MV photon
energies. All patients were optimized with the same planning objectives and
normalized such that 95% of the planning target volume (PTV) received the
prescription dose. Patients were evaluated for PTV and organ at risk (OAR)
parameters for the bladder, rectum, small bowel, penile bulb, and sigmoid colon.
Metrics used for comparison were D2%, D98%, homogeneity, conformity, and dose
falloff for the PTV and D(2%), D(mean), V(80%), V(60%), and V(40%) for OARs.
Statistical differences were evaluated with a paired-sample Wilcoxon signed rank
test with a significance level of .05. RESULTS: For the PTV, there were no
statistically significant differences in D(mean), D(2cc), conformation number,
and homogeneity index values, but the dose falloff parameters, R50 and R25,
showed a median improvement of 6.7% (P<.01) and 6.2% (P<.01), respectively, with
10 MV. A correlation between patient anterior-posterior distance (d(AP)) and
percentage reduction in R50 of 0.436% per centimeter (P<.01) was determined. For
OARs, statistically significant reductions in dose metrics were found in the
small bowel and bladder, but increases in the D(2cc) of 3.5% in the penile bulb
(P<.01) and 0.2% in the rectum (P=.02) were shown with 10 MV. The use of 10 MV
also demonstrated a statistically significant reduction in the total number of
monitor units of 15.9% (P<.01) compared with 6 MV. CONCLUSIONS: The study showed
that 10 MV provides a faster dose falloff than 6 MV for patients whose prostate
and pelvic lymph nodes are treated using a VMAT technique irrespective of body
habitus; however, the improvement in dose falloff is dependent on body habitus
and increases as the patient body habitus increases.
PMID- 26419444
TI - Four dimensional magnetic resonance imaging optimization and implementation for
magnetic resonance imaging simulation.
AB - PURPOSE: Precise radiation therapy for abdominal lesions is complicated by
respiratory motion and suboptimal soft tissue contrast from 4-dimensional (4D)
computed tomography, whereas 4D magnetic resonance imaging MRI (4DMRI) provides
superior tissue discrimination. This work evaluates a novel 4DMRI algorithm for
motion management in radiation therapy. METHODS AND MATERIALS: Respiratory
triggered, T2-weighted, single-shot 4DMRI was evaluated for an open 1.0T magnetic
resonance simulation platform. An in-house programmable platform was devised that
translated objects for a variety of breathing patterns. Coronal 4DMRIs were
acquired to evaluate the impact of number of phases on excursion and scan time.
The impact of breathing period and regularity on scan time was assessed. A novel
clinical 4D prototype phantom was scanned to characterize excursion and absolute
volume differences between phase acquisitions. Optimized parameters were applied
to abdominal 4DMRIs of 5 volunteers and 2 abdominal cancer patients on an
institutional review board-approved protocol. Duty cycle, scan time, and waveform
analysis were evaluated. Maximum intensity projection datasets were analyzed.
RESULTS: Two- to 5-fold acquisition time increase was measured for 10-phase
versus 2-phase phantom experiments. Regular breathing patterns yielded higher
duty cycles than irregular (48.5% and 35.9%, respectively, P < .001), whereas
faster breathing rates yielded shorter 4DMRI acquisition times. Volumes of a
hypodense target were underestimated 4% to 5% for 2 and 4 phases compared with 10
phases. Better agreement was obtained for 6- and 8-phase acquisitions (~3%
different from 10 phase). Internal target volume centroids on minimum and maximum
images across all phases were <2 mm different across all 10 phases, although
slight target excursion variations (up to 4 mm) were observed. In humans, a
strong negative association between breathing rate and acquisition time
(Pearson's r = -0.68, P < .05) was observed. Eight-phase acquisition times ranged
from 7 to 15 minutes, depending on the patient. CONCLUSION: 4DMRI has been
optimized and implemented. Irregular breathing patterns and slow breathing rate
adversely impacted 4DMRI efficiency; thus, interventions such as biofeedback may
be desirable.
PMID- 26419445
TI - Transferrin Receptor 1 in Chronic Hypoxia-Induced Pulmonary Vascular Remodeling.
AB - BACKGROUND: Iron is associated with the pathophysiology of several cardiovascular
diseases, including pulmonary hypertension (PH). In addition, disrupted pulmonary
iron homeostasis has been reported in several chronic lung diseases. Transferrin
receptor 1 (TfR1) plays a key role in cellular iron transport. However, the role
of TfR1 in the pathophysiology of PH has not been well characterized. In this
study, we investigate the role of TfR1 in the development of hypoxia-induced
pulmonary vascular remodeling. METHODS: PH was induced by exposing wild-type (WT)
mice and TfR1 hetero knockout mice to hypoxia for 4 weeks and evaluated via
assessment of pulmonary vascular remodeling, right ventricular (RV) systolic
pressure, and RV hypertrophy. In addition, we assessed the functional role of
TfR1 in pulmonary artery smooth muscle cells in vitro. RESULTS: The morphology of
pulmonary arteries did not differ between WT mice and TfR1 hetero knockout mice
under normoxic conditions. In contrast, TfR1 hetero knockout mice exposed to 4
weeks hypoxia showed attenuated pulmonary vascular remodeling, RV systolic
pressure, and RV hypertrophy compared with WT mice. In addition, the depletion of
TfR1 by RNA interference attenuated human pulmonary artery smooth muscle cells
proliferation induced by platelet-derived growth factor-BB (PDGF-BB) in vitro.
CONCLUSIONS: These results suggest that TfR1 plays an important role in the
development of hypoxia-induced pulmonary vascular remodeling.
PMID- 26419446
TI - Educational attainment and health transitions over the life course: testing the
potential mechanisms.
AB - BACKGROUND: It has been shown that higher education associates with health
outcomes, but the less is known about the specific mechanisms mediating this
association. We examined whether higher education would associate with long-term
health transitions from childhood to adulthood and whether health behaviors, self
esteem, social support and work-related health hazards could mediate or confound
this association. METHODS: The participants were from a population-based sample
of 3596 men and women from the Young Finns study aged 3-18 years at the beginning
of the study in 1980, and who responded to repeated surveys of educational
attainment and self-rated health in four study phases from 1997 to 2012. The
associations were tested using multistate Markov models for the health-state
transition intensities. RESULTS: Our results suggested that a 1-year difference
in education was related to a 16% higher transition probability from mediocre to
good self-rated health over the 5-year follow-up. Depressive symptoms and job
strain seemed to partly mediate or confound the association, but self-esteem and
social support did not. CONCLUSIONS: These results suggest that educational
attainment is associated with good self-rated health transitions from childhood
to adulthood, and multiple processes rather than a single underlying mechanism
are likely to drive the educational differences in self-rated health.
PMID- 26419447
TI - Therapeutic Potential of alpha7 Nicotinic Acetylcholine Receptors.
AB - Progress in the fields of neuroscience and molecular biology has identified the
forebrain cholinergic system as being important in many higher order brain
functions. Further analysis of the genes encoding the nicotinic acetylcholine
receptors (nAChRs) has highlighted, in particular, the role of alpha7 nAChRs in
these higher order brain functions as evidenced by their peculiar physiologic and
pharmacological properties. As this receptor has gained the attention of
scientists from academia and industry, our knowledge of its roles in various
brain and bodily functions has increased immensely. We have also seen the
development of small molecules that have further refined our understanding of the
roles of alpha7 nAChRs, and these molecules have begun to be tested in clinical
trials for several indications. Although a large body of data has confirmed a
role of alpha7 nAChRs in cognition, the translation of small molecules affecting
alpha7 nAChRs into therapeutics has to date only progressed to the stage of
testing in clinical trials. Notably, however, most recent human genetic and
biochemical studies are further underscoring the crucial role of alpha7 nAChRs
and associated genes in multiple organ systems and disease states. The aim of
this review is to discuss our current knowledge of alpha7 nAChRs and their
relevance as a target in specific functional systems and disease states.
PMID- 26419448
TI - Rho Kinases in Health and Disease: From Basic Science to Translational Research.
AB - Rho-associated kinases ROCK1 and ROCK2 are key regulators of actin cytoskeleton
dynamics downstream of Rho GTPases that participate in the control of important
physiologic functions, S including cell contraction, migration, proliferation,
adhesion, and inflammation. Several excellent review articles dealing with ROCK
function and regulation have been published over the past few years. Although a
brief overview of general molecular, biochemical, and functional properties of
ROCKs is included, an effort has been made to produce an original work by
collecting and synthesizing recent studies aimed at translating basic discoveries
from cell and experimental models into knowledge of human physiology,
pathophysiological mechanisms, and medical therapeutics. This review points out
the specificity and distinct roles of ROCK1 and ROCK2 isoforms highlighted in the
last few years. Results obtained from genetically modified mice and genetic
analysis in humans are discussed. This review also addresses the involvement of
ROCKs in human diseases and the potential use of ROCK activity as a biomarker or
a pharmacological target for specific inhibitors.
PMID- 26419449
TI - Approaches used by parents to keep their children safe at home: a qualitative
study to explore the perspectives of parents with children aged under five years.
AB - BACKGROUND: Childhood unintentional injury represents an important global health
problem. Many unintentional injuries experienced by children aged under 5 years
occur within the home and are preventable. The aim of this study was to explore
the approaches used by parents of children under five in order to help prevent
unintentional injuries in the home and the factors which influence their use.
Understanding how parents approach risk-management in the home has important
implications for injury practitioners. METHODS: A multi-centre qualitative study
using semi-structured interviews. A thematic approach was used to analyse the
data. Sixty five parents of children aged under 5 years, from four study areas
were interviewed: Bristol, Newcastle, Norwich and Nottingham. RESULTS: Three main
injury prevention strategies used by parents were: a) Environmental such as
removal of hazards, and use of safety equipment; b) parental supervision; and c)
teaching, for example, teaching children about safety and use of rules and
routine. Strategies were often used in combination due to their individual
limitations. Parental assessment of injury risk, use of strategy and perceived
effectiveness were fluid processes dependent on a child's character,
developmental age and the prior experiences of both parent and child. Some
parents were more proactive in their approach to home safety while others only
reacted if their child demonstrated an interest in a particular object or
activity perceived as being an injury risk. CONCLUSION: Parents' injury
prevention practices encompass a range of strategies that are fluid in line with
the child's age and stage of development; however, parents report that they still
find it challenging to decide which strategy to use and when.
PMID- 26419450
TI - Population pharmacokinetics and pharmacodynamics of busulfan with GSTA1
polymorphisms in patients undergoing allogeneic hematopoietic stem cell
transplantation.
AB - AIM: A population pharmacokinetic (PPK) analysis was conducted to describe the
influence of GSTA1 polymorphisms on intravenous busulfan in adults undergoing
allogeneic hematopoietic stem cell transplantation. PATIENTS & METHODS: A PPK
model was developed from 36 patients by a one-compartment model with first-order
elimination. RESULTS: The typical value of clearance and volume of distribution
were 11.0 l/h and 42.4 l, respectively. Clearance decreased by 15% and area under
the concentration-time curves (AUCs) increased with GSTA1 variants compared with
wild-type (both p < 0.05). Subtherapeutic AUCs were seen only in wild-type
patients. CONCLUSION: To our knowledge, this is the first PPK study to suggest
that GSTA1 polymorphisms in adults are associated with busulfan PK.
PMID- 26419452
TI - Metabolomic charactetization of yeast cells after dehydration stress.
AB - In this study, we analyzed the metabolite features of the yeasts Saccharomyces
cerevisiae, Naumovia castellii, and Saccharomyces mikatae. The three species are
closely related genetically but differ in their tolerance of desiccation stress.
Specifically, we determined whether certain metabolites correlated with cell
viability after stress imposition. The metabolomics profiles of these strains
were compared before cell desiccation and after cell rehydration. In S. mikatae,
the presence of lysine or glutamine during rehydration led to a 20% increase in
survival whereas during dehydration the levels of both amino acids in this yeast
were drastically reduced.
PMID- 26419451
TI - RIFM fragrance ingredient safety assessment, isoamyl salicylate, CAS registry
number 87-20-7.
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 toxicity, reproductive toxicity, local respiratory
toxicity, phototoxicity, skin sensitization potential, as well as, environmental
safety. Repeated dose toxicity was determined using to have the most conservative
systemic exposure derived NOAEL of 47 mg/kg/day. A dietary 13-week subchronic
toxicity study conducted in rats on a suitable read across analog resulted in a
MOE of 2350 while considering 10.3% absorption from skin contact and 100% from
inhalation. A MOE of >100 is deemed acceptable.
PMID- 26419453
TI - Identification of a class B acid phosphatase in Haemophilus parasuis.
AB - An acid phosphatase activity was detected in the supernatant of Haemophilus
parasuis, a Gram-negative pleomorphic bacillus and the causative agent of
Glasser's disease in pigs. To identify the gene responsible for the secreted
activity, a genomic library of H. parasuis strain ER-6P was produced in
Escherichia coli. Screening of the library allowed identification of two homologs
to known phosphatases: PgpB and AphA. PgpB was predicted to be located in the
bacterial membrane through six transmembrane domains while AphA was predicted to
have a signal peptide. The aphA gene was cloned and expressed in E. coli.
Characterization of H. parasuis AphA indicated that this protein belongs to the
class B nonspecific acid phosphatases. AphA contained sequence signatures
characteristic of this family of phosphatases and its activity was inhibited by
EDTA. The optimal pH of recombinant AphA differed from that of the phosphatase
activity found in H. parasuis supernatants. In addition, the phosphatase activity
from H. parasuis supernatants was not inhibited by EDTA, indicating that H.
parasuis AphA does not account for the phosphatase activity observed in the
supernatants. Our results demonstrate the presence of a class B acid phosphatase
(AphA) in H. parasuis and suggest that the bacterium would also secrete another,
as yet unidentified phosphatase.
PMID- 26419454
TI - Molecular epidemiology of methicillin-resistant Staphylococcus aureus in a
university hospital in northwestern Spain.
AB - Continuous monitoring of methicillin-resistant Staphylococcus aureus (MRSA) is
necessary to understand the clonal evolution of successful lineages. In this
study, we identified the MRSA clones circulating in a Spanish hospital during a 2
year period, assessed their relationship with antimicrobial resistance profiles,
and investigated the presence of the emerging community-associated and livestock
associated MRSA lineages (CA-MRSA, LA-MRSA). CC5-MRSA-IV isolates were the most
frequently recovered, which supports the previously reported prevalence of this
clone in Spanish hospitals. We observed ST125 isolates that harbored specific
cassette chromosome recombinase (ccr) gene elements of the staphylococcal
cassette chromosome mec (SCCmec) types IV and VI. That clone, which was first
detected only recently, has increased resistance to erythromycin. Furthermore,
94% of the infections were caused by non-multiresistant isolates. Neither CA-MRSA
nor LA-MRSA isolates were observed. These findings, along with related events
over the last decade, suggest the establishment of a clonal endemic population in
the Spanish clinical environment.
PMID- 26419455
TI - Significance of tagI and mfd genes in the virulence of non-typeable Haemophilus
influenzae.
AB - Non-typeable Haemophilus influenzae (NTHi) is an opportunist pathogen well
adapted to the human upper respiratory tract and responsible for many respiratory
diseases. In the human airway, NTHi is exposed to pollutants, such as alkylating
agents, that damage its DNA. In this study, we examined the significance of genes
involved in the repair of DNA alkylation damage in NTHi virulence. Two knockout
mutants, tagI and mfd, encoding N3-methyladenine-DNA glycosylase I and the key
protein involved in transcription-coupled repair, respectively, were constructed
and their virulence in a BALB/c mice model was examined. This work shows that N3
methyladenine-DNA glycosylase I is constitutively expressed in NTHi and that it
is relevant for its virulence.
PMID- 26419456
TI - Endophytic and rhizospheric bacterial communities isolated from the medicinal
plants Echinacea purpurea and Echinacea angustifolia.
AB - In this work we analyzed the composition and structure of cultivable bacterial
communities isolated from the stem/leaf and root compartments of two medicinal
plants, Echinacea purpurea (L.) Moench and Echinacea angustifolia (DC.) Hell,
grown in the same soil, as well as the bacterial community from their
rhizospheric soils. Molecular PCR-based techniques were applied to cultivable
bacteria isolated from the three compartments of the two plants. The results
showed that the two plants and their respective compartments were characterized
by different communities, indicating a low degree of strain sharing and a strong
selective pressure within plant tissues. Pseudomonas was the most highly
represented genus, together with Actinobacteria and Bacillus spp. The presence of
distinct bacterial communities in different plant species and among compartments
of the same plant species could account for the differences in the medicinal
properties of the two plants.
PMID- 26419457
TI - A glucuronoxylan-specific xylanase from a new Paenibacillus favisporus strain
isolated from tropical soil of Brazil.
AB - A new xylanolytic strain, Paenibacillus favisporus CC02-N2, was isolated from
sugarcane plantation fields in Brazil. The strain had a xylan-degrading system
with multiple enzymes, one of which, xylanase Xyn30A, was identified and
characterized. The enzyme is a single-domain xylanase belonging to family 30 of
the glycosyl hydrolases (GH30). Xyn30A shows high activity on glucuronoxylans,
with a Vmax of 267.2 U mg-1, a Km of 4.0 mg/ml, and a kcat of 13,333 min-1 on
beechwood xylan, but it does not hydrolyze arabinoxylans. The three-dimensional
structure of Xyn30A consists of a common (beta/alpha)8 barrel linked to a side
chain-associated beta-structure, similar to previously characterized GH30
xylanases. The hydrolysis products from glucuronoxylan were methylglucuronic-acid
substituted xylooligomers (acidic xylooligosaccharides). The enzyme bound to
insoluble xylan but not to crystalline cellulose. Our results suggest a specific
role for Xyn30A in xylan biodegradation in natural habitats. The enzyme is a good
candidate for the production of tailored xylooligosaccharides for use in the food
industry and in the biotechnological transformation of biomass.
PMID- 26419458
TI - Physical rehabilitation interventions for adult patients with critical illness
across the continuum of recovery: an overview of systematic reviews protocol.
AB - BACKGROUND: Patients admitted to the intensive care unit with critical illness
often experience significant physical impairments, which typically persist for
many years following resolution of the original illness. Physical rehabilitation
interventions that enhance restoration of physical function have been evaluated
across the continuum of recovery following critical illness including within the
intensive care unit, following discharge to the ward and beyond hospital
discharge. Multiple systematic reviews have been published appraising the
expanding evidence investigating these physical rehabilitation interventions,
although there appears to be variability in review methodology and quality. We
aim to conduct an overview of existing systematic reviews of physical
rehabilitation interventions for adult intensive care patients across the
continuum of recovery. METHODS/DESIGN: This protocol has been developed according
to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Protocol (PRISMA-P) guidelines. We will search the Cochrane Systematic Review
Database, Database of Abstracts of Reviews of Effectiveness, Cochrane Central
Register of Controlled Trials, MEDLINE, Excerpta Medica Database and Cumulative
Index to Nursing and Allied Health Literature databases. We will include
systematic reviews of randomised controlled trials of adult patients, admitted to
the intensive care unit and who have received physical rehabilitation
interventions at any time point during their recovery. Data extraction will
include systematic review aims and rationale, study types, populations,
interventions, comparators, outcomes and quality appraisal method. Primary
outcomes of interest will focus on findings reflecting recovery of physical
function. Quality of reporting and methodological quality will be appraised using
the PRISMA checklist and the Assessment of Multiple Systematic Reviews tool.
DISCUSSION: We anticipate the findings from this novel overview of systematic
reviews will contribute to the synthesis and interpretation of existing evidence
regarding physical rehabilitation interventions and physical recovery in post
critical illness patients across the continuum of recovery. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO CRD42015001068.
PMID- 26419459
TI - Long-term Outcomes in Steroid-refractory Ulcerative Colitis Treated with
Tacrolimus Alone or in Combination with Purine Analogues.
AB - BACKGROUND AND AIMS: Tacrolimus is recommended for the treatment of steroid
refractory ulcerative colitis (UC). Concomitantly started purine analogues (PAs)
are used for the maintenance of remission, though their therapeutic relevance
remains uncertain. Here we studied the role of PAs in the long-term outcome of
steroid-refractory UC after tacrolimus treatment. METHODS: In five centres,
charts of tacrolimus-treated UC patients with a steroid-refractory moderate to
severe course were reviewed. Long-term efficacy was determined by colectomy rates
and clinical remission in cases of colectomy-free survival for 3 months. RESULTS:
We identified 156 patients (median age 34 years) with a median Lichtiger score of
12 (4-17) and pancolitis (E3) in 65% (101). The Kaplan-Meier curve for colectomy
free survival after month 3 showed a benefit in the PA group (p = 0.02). In
patients treated with PA clinical remission was achieved in 82% (65/79) vs 67%
(39/58) in those not treated with PA (p = 0.02). Time to colectomy was 2 years
(median, 0.7-5.8) in the PA group and 0.8 years (0.3-4.7) in the group not
treated with PAs (p = 0.02). Time to relapse was 1.2 years (median, 0.3-6.2) in
patients with PA treatment and 0.5 years (0.3-3.9) in those without PA treatment
(p = 0.05). Overall, clinical remission was achieved in 67% (104/156) of
patients. Colectomy was performed in 29% (45/156) 0.5 years (median, 0.04-5.79)
after initiation of tacrolimus. Ten (6%) patients had to stop tacrolimus due to
adverse events and two (without PA treatment) died. CONCLUSIONS: Our study
supports the efficacy of tacrolimus in steroid-refractory UC. Purine analogues
appear to be beneficial for the long-term outcome of these patients.
PMID- 26419461
TI - Extensive Neuroendocrine Adenocarcinoma in Ulcerative Colitis.
PMID- 26419460
TI - DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights
into Disease Pathogenesis.
AB - BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) are heterogeneous
disorders with complex aetiology. Quantitative genetic studies suggest that only
a small proportion of the disease variance observed in IBD is accounted for by
genetic variation, indicating a potential role for differential epigenetic
regulation in disease aetiology. The aim of this study was to assess genome-wide
DNA methylation changes specifically associated with ulcerative colitis (UC),
Crohn's disease (CD) and IBD activity. METHODS: DNA methylation was quantified in
peripheral blood mononuclear cells (PBMCs) from 149 IBD cases (61 UC, 88 CD) and
39 controls using the Infinium HumanMethylation450 BeadChip. Technical and
functional validation was performed using pyrosequencing and the real-time
polymerase chain reaction. Cross-tissue replication of the top differentially
methylated positions (DMPs) was tested in colonic mucosa tissue samples obtained
from paediatric IBD cases and controls. RESULTS: A total of 3196 probes were
differentially methylated between CD cases and controls, while 1481 probes were
differentially methylated between UC cases and controls. There was considerable
(45%) overlap between UC and CD DMPs. The top-ranked IBD-associated PBMC
differentially methylated region (promoter region of TRIM39-RPP2) was also
significantly hypomethylated in colonic mucosa from paediatric UC patients. In
addition, we confirmed TRAF6 hypermethylation using pyrosequencing and found
reduced TRAF6 gene expression in PBMCs of IBD patients. CONCLUSIONS: Our data
provide new insights into differential epigenetic regulation of genes and
molecular pathways, which may contribute to the pathogenesis and activity of IBD.
PMID- 26419462
TI - Risk factors of acute myocardial infarction in middle-aged and adolescent people
(< 45 years) in Yantai.
AB - BACKGROUND: Yantai is a developed medium-sized coastal city in Eastern China,
having a population of 1.6845 million. With the development of economy, some
middle-aged and adolescent people (< 45 years) devote themselves to work and
suffer from greater stress, which makes them ignore their own health. Moreover,
they have unhealthy lifestyles and lack the knowledge of cardiovascular risk
factors. OBJECTIVES: To identify the risk factors for first acute myocardial
infarction in middle-aged and adolescent people in Yantai, a developed medium
sized coastal city in Eastern China. METHODS: A total of 154 consecutive patients
with first acute myocardial infarction (< 45 years), were enrolled in case group,
and 462 patients without myocardial infarction were enrolled in control group.
Three controls with the same sex and age were matched to each case. The risk
factors were identified with univariate and multivariate analysis. RESULTS:
Unhealthy food habit (eating seafood and meanwhile drinking beer), hypertension,
current smokers, self-perceived stress, diabetes mellitus, obesity, sleep
insufficience, hypercholesterolaemia and fatigue were independent risk factors
for first acute myocardial infarction (P < 0.05). CONCLUSIONS: Besides those
recognized risk factors for cardiovascular disease (hypertension,
hypercholesterolemia, diabetes mellitus and smoking), eating seafood and
meanwhile drinking beer, self-perceived stress, sleep insufficience, obesity and
fatigue were also the risk factors for first acute myocardial infarction in
middle-aged and adolescent people in Yantai.
PMID- 26419463
TI - Disease proportions and drug prescribing pattern observed in a free health camp
organized at Dhorphirdi Village Development Committee of Western Nepal.
AB - BACKGROUND: Health camp is generally organized to provide health care services to
the people deprived of health care facilities. The aim of this project was to
assess the proportions of disease among attendees of health camp and study the
drug prescribing pattern in a free health camp. METHODS: A case study was
performed from 1 day health camp to determine the proportions of disease and drug
prescribing pattern. Data collection was performed using log book maintained in
the health camp and patient's demographic details, disease diagnosed and drug
prescribed was obtained from same log book. RESULTS: A total of 317 patients were
included in the study. The majority of the patients were in the range of 41-50
years. On the basis of study on ethnicity, Brahmins and Chettris, were found to
be predominant ethnic groups with gastrointestinal disorders as the major
disease. The total number of medications prescribed was 510, with non-steroidal
anti-inflammatory drugs (NSAIDs) and antipeptic ulcer drugs being commonly
prescribed. The average number of drugs per prescription and the percentage of
antibiotics prescribed were 1.6 and 21.4%, respectively. It was observed that
96.8% of prescription was by generic names. Likewise, 100% of prescription
included drugs from essential drug list. CONCLUSION: Majority of the patients
were of working age group. Headache and fever were found to be the most prevalent
cases and NSAIDs were the most commonly prescribed medications. The drug
prescribing pattern of the free health camp complied with WHO recommended
prescribing indicators.
PMID- 26419464
TI - Primary erythromelalgia: a review.
AB - Primary erythromelalgia (PE ORPHA90026) is a rare autosomal dominant neuropathy
characterized by the combination of recurrent burning pain, warmth and redness of
the extremities. The incidence rate of PE ranges from 0.36 to 1.1 per 100,000
persons. Gender ratio differs according to different studies and no evidence
showed a gender preference. Clinical onset of PE is often in the first decade of
life. Burning pain is the most predominant symptom and is usually caused and
precipitated by warmth and physical activities. Reported cases of PE contain both
inherited and sporadic forms. Genetic etiology of PE is mutations on SCN9A, the
encoding gene of a voltage-gated sodium channel subtype Nav1.7. Diagnosis of PE
is made upon clinical manifestations and screening for mutations on SCN9A.
Exclusion of several other treatable diseases/secondary erythromelalgia is also
necessary because of the lack of biomarkers specifically for PE. Differential
diagnoses can include Fabry disease, cellulites, Raynaud phenomenon, vasculitis
and so on. Diagnostic methods often involve complete blood count, imaging studies
and thermograph. Treatment for PE is unsatisfactory and highly individualized.
Frequently used pain relieving drugs involve sodium channel blockers such as
lidocaine, carbamazepine and mexiletine. Novel drugs such as PF-05089771 and TV
45070 could be promising in ameliorating pain symptoms due to their Nav1.7
selectivity. Patients' symptoms often worsen over time and many patients develop
ulcerations and gangrenes caused by excessive exposure to low temperature in
order to relieve pain. This review mainly focuses on PE and the causative gene
SCN9A--its mutations and their effects on Nav1.7 channels' electrophysiological
properties. We propose a genotype-channelopathy-phenotype correlation network
underlying PE etiology which could provide guidance for future therapeutics.
PMID- 26419465
TI - Dynamic alteration of serum testosterone with aging: a cross-sectional study from
Shanghai, China.
AB - BACKGROUND: Level of the testosterone in a man's life span is very important.
Studies on the serum testosterone concentrations in different age groups of
healthy men were controversial. The aim of this study was to investigate dynamic
changes of serum reproductive hormones with aging in healthy Chinese male and to
compare its correlation with age. METHODS: Total of 1,093 healthy Chinese men
from Shanghai aged from 20 to 87 years old was enrolled in the study.
Concentrations of serum total testosterone (T), luteinizing hormone (LH) and sex
hormone binding globulin (SHBG) were quantified by EIA. Testosterone secretion
index (TSI) and free testosterone index (FTI) were then calculated. Data were
analyzed by SPSS program. Non-parametric tests and univariate linear regression
analyses were used. RESULTS: The 1,039 male participants were grouped into 12
groups by 5-year apart for each group. Significant differences in T, LH, SHBG,
FTI and TSI were found between the 12 different age groups. Average of serum
total T was 15.36 +/- 4.86 nmol/L; LH was 4.76 +/- 2.76 IU/L, SHBG was 32.61 +/-
17.24 nmol/L. Compared to age 20 ~ 24 group, serum T level of age 35 ~ 39, 40 ~
44, 45 ~ 49, 50 ~ 54, and 55 ~ 59 was significantly decreased (p < 0.05).
Intriguingly, however, serum T level of age 60 or older did not significantly
reduced compared to the age of 20 ~ 24 group. Serum LH and SHBG were positively
correlated with aging (p <0.01), while TSI and FTI were negatively correlated
with aging (p <0.01). In addition, BMI was negatively and significantly
correlated with levels of T (r = -0.585, p < 0.001), LH (r = -0.090, p < 0.001),
SHBG (r = - 1.817, p < 0.001), and TSI (r = - 0.104, p < 0.001), but positively
and significantly correlated with FTI level (r = 0.011, p < 0.001). CONCLUSION:
Serum total testosterone fluctuated with aging in adult men, and FTI and TSI
decreased gradually with aging. While age was not significantly correlated with T
level, BMI was significantly and negatively correlated with T level, suggesting
body weight may affect testosterone level.
PMID- 26419466
TI - Prebiotic and Probiotic Regulation of Bone Health: Role of the Intestine and its
Microbiome.
AB - Recent advances in our understanding of how the intestinal microbiome contributes
to health and disease have generated great interest in developing strategies for
modulating the abundance of microbes and/or their activity to improve overall
human health and prevent pathologies such as osteoporosis. Bone is an organ that
the gut has long been known to regulate through absorption of calcium, the key
bone mineral. However, it is clear that modulation of the gut and its microbiome
can affect bone density and strength in a variety of animal models (zebrafish,
rodents, chicken) and humans. This is demonstrated in studies ablating the
microbiome through antibiotic treatment or using germ-free mouse conditions as
well as in studies modulating the microbiome activity and composition through
prebiotic and/or probiotic treatment. This review will discuss recent
developments in this new and exciting area.
PMID- 26419468
TI - Research Progress on the Antitumor Effects of Rhein: Literature Review.
AB - BACKGROUND: Rhein (1,8-dihydroxy-3-carboxyanthraquinone) is a monomer of
anthraquinone derivatives mainly found in Polygonaceae plants such as Rhubarb,
and Cuspidatum, widely used in the traditional Chinese medicine with many
pharmacological activities, such as antitumor, anti-inflammatory and antifibrotic
effects, and regulation of glucose and lipid metabolism. OBJECTIVE: To conclude
the role of Rhein in cancer control and its mechanisms for its futher deep
research and potential clinical application. METHOD: All kinds of reports
previously related to Rhein from PubMed datebase were collected, integrated and
analyzed. RESULTS: Rhein could control many cancer cells by regulating their
proliferation and apoptosis, invasion and migration, especially intrinsic and
extrinsic apoptosis pathways induced by Rhein plays the core role in cancer
control. For good inhibitory role in NF-kappaB pathway, the Ras/Raf/MEK
(MAPK)/ERK and PTEN/PI3K/AKT/mTOR pathways are other two key pathways regulated
by Rhein with its role in antiphosphorylation of ERK, PI3K and AKT to control
many cancers' development which frequently dysregulated in cancer, involved in
the activation, proliferation, invasion, and migration of cancer cells.
CONCLUSION: Rhein is a potential cancer treatment agent.
PMID- 26419467
TI - A Mechanism-Based Approach to the Management of Osteoarthritis Pain.
AB - Pain from osteoarthritis (OA) affects millions of people worldwide, yet
treatments are limited to acetaminophen, NSAIDs, physical therapy, and
ultimately, surgery when there is significant disability. In recent years, our
understanding of pain pathways in OA has developed considerably. Though joint
damage and inflammation play a significant role in pain generation, it is now
understood that both central and peripheral nervous system mechanisms exacerbate
symptoms. Evolving management strategies for OA address central factors (e.g.,
sleep difficulties, catastrophizing, and depression) with treatments such as
cognitive behavioral therapy and exercise. In addition, emerging data suggest
that antibodies against peripheral signaling neuropeptides, such as nerve growth
factor-1 (NGF-1), may significantly alleviate pain. However, concerns regarding
potential adverse effects, such as rapidly progressive OA, still remain. A
nuanced understanding is essential if we are to make headway in developing more
effective treatments for OA.
PMID- 26419469
TI - Implication of Unfolded Protein Response and Autophagy in the Treatment of BRAF
Inhibitor Resistant Melanoma.
AB - The continuous activation of the mitogen-activated protein kinase signaling
cascade, typified by the BRAFV600E mutation, is one of the key alterations in
melanoma. Accordingly, two BRAF inhibitors (BRAFi), vemurafenib and dabrafenib
are utilized to treat melanoma and resulted in an excellent clinical outcome.
However, the clinical success is not long-lasting, and the BRAFi resistance and
disease progression inevitably occurs in nearly all patients. Endoplasmic
reticulum stress-induced unfolded protein response and autophagy have emerged as
potential pro-survival mechanisms adopted by melanoma cells in response to BRAFi.
In this review, we discuss the role of unfolded protein response and autophagy
that are implicated in the development of BRAFi-resistant melanoma and the
corresponding strategy aiming at overcoming the intractable clinical problem.
PMID- 26419470
TI - Opportunistic screening for osteoporosis using the sagittal reconstruction from
routine abdominal CT for combined assessment of vertebral fractures and density.
AB - SUMMARY: Opportunistic osteoporosis screening using abdominal CT scans obtained
for other purposes has the potential to increase detection of those at increased
risk for fragility fractures. We sought to combine the tasks of density
measurement and vertebral fracture assessment on the sagittal view. We confirm
that this represents a robust approach and recommend its implementation in
clinical practice. INTRODUCTION: Opportunistic osteoporosis screening at routine
abdominal CT has been proposed by measuring axial (transverse) L1 trabecular
attenuation and by sagittal reconstruction for vertebral fracture assessment. We
sought to combine this dual evaluation on the sagittal reconstruction alone to
improve efficiency. METHODS: Routine contrast-enhanced abdominal CT scans
performed for any indication on 571 consecutive adults age 60 years or older
(mean age 70.7 years) were retrospectively analyzed. These were performed at a
single center over a 3-month period. L1 trabecular attenuation was measured using
an ovoid region-of-interest on both the transverse and sagittal series. The
sagittal reconstruction was also analyzed for moderate-to-severe vertebral
compression fractures using the Genant visual semi-quantitative method. Likely
osteoporosis was defined by a moderate-to-severe fracture and/or sagittal L1
trabecular attenuation of <=110 Hounsfield units (HU) (previously found to be
>90% specific for osteoporosis on our calibrated GE CT scanners at 120 kV(p)).
Correlation was made with hip and spine dual X-ray absorptiometry (DXA). RESULTS:
Mean absolute difference in L1 trabecular attenuation between transverse and
sagittal reconstructions was 6.7 HU (+/-5.7) or 6.2%. The transverse and sagittal
HU measurements were in agreement (i.e., both measurements above or below this
threshold) in 94.5% of cases at the 110-HU cutoff. A total of 243 (42.3%)
patients had likely osteoporosis by CT criteria, of which only 48 (19.8%) had
previous DXA screening. CONCLUSION: Assessment of the sagittal view alone at
routine abdominal CT for both vertebral fractures and trabecular bone mineral
density provides a rapid and effective opportunistic screen for detecting
individuals at increased risk for fragility fractures.
PMID- 26419472
TI - Introduction: Regulatory B Cell Special Issue-making all the pieces fit.
PMID- 26419476
TI - Establishment from the snout and kidney of goldfish, Carassius auratus, of two
new cell lines and their susceptibility to infectious pancreatic necrosis virus.
AB - Goldfish Carassius auratus are commonly used in scientific research and have a
significant economic value in the pet trade. In this study, two cell lines were
established from the snout and kidney tissue of goldfish, in order to create a
biological monitoring tool for viral diseases. Cell lines were optimally
maintained at 25 degrees C in M199 medium supplemented with 15-20 % fetal bovine
serum. Chromosomal analysis indicated that both cell lines remained diploid, with
a mean chromosomal count of 100. Results of viral inoculation assays revealed
that both cell lines shared similar patterns of viral susceptibility and
production to infectious pancreatic necrosis virus (IPNV). The viral titers of
IPNV in goldfish snout cell line (GFSe) and goldfish kidney cell line (GFKf)
reached 10(6.8) and 10(5.9) TCID50/0.1 mL, respectively, within 7 days. The
cytopathic effect could be observed when Cyprinid herpesvirus 2 was inoculated
into these cells; however, the CPE disappeared after four passages. No CPE was
observed in the cells infected by spring viremia carp virus or grass carp
reovirus. These newly established cell lines will be a useful diagnostic tool for
viral diseases in this fish species and also for the isolation and study of
goldfish viruses in future.
PMID- 26419477
TI - Molecular signatures that are distinctive characteristics of the vertebrates and
chordates and supporting a grouping of vertebrates with the tunicates.
AB - Members of the phylum Chordata and the subphylum Vertebrata are presently
distinguished solely on the basis of morphological characteristics. The
relationship of the vertebrates to the two non-vertebrate chordate subphyla is
also a subject of debate. Analyses of protein sequences have identified multiple
conserved signature indels (CSIs) that are specific for Chordata or for
Vertebrata. Five CSIs in 4 important proteins are specific for the Vertebrata,
whereas two other CSIs are uniquely found in all sequenced chordate species
including Ciona intestinalis and Oikapleura dioica (Tunicates) as well as
Branchiostoma floridae (Cephalochordates). The shared presence of these molecular
signatures by all vertebrates/chordate species, but in no other animal taxa,
strongly indicates that the genetic changes represented by the identified CSIs
diagnose monophyletic groups. Two other discovered CSIs are uniquely shared by
different vertebrate species and by either one (Ciona intestinalis) or both
tunicate (Ciona and Oikapleura) species, but they are not found in Branchiostoma
or other animal species. Specific presence of these CSIs in different vertebrates
and either one or both tunicate species provides strong independent evidence that
the vertebrate species are more closely related to the urochordates (tunicates)
than to the cephalochordates.
PMID- 26419471
TI - Effect of osteoporosis medications on fracture healing.
AB - Antiosteoporotic medications are often used to concurrently treat a patient's
fragility fractures and underlying osteoporosis. This review evaluates the
existing literature from animal and clinical models to determine these drugs'
effects on fracture healing. The data suggest that these medications may enhance
bone healing, yet more thorough prospective studies are warranted. Pharmacologic
agents that influence bone remodeling are an essential component of osteoporosis
management. Because many patients are first diagnosed with osteoporosis when
presenting with a fragility fracture, it is critical to understand how
osteoporotic medications influence fracture healing. Vitamin D and its analogs
are essential for the mineralization of the callus and may also play a role in
callus formation and remodeling that enhances biomechanical strength. In animal
models, antiresorptive medications, including bisphosphonates, denosumab,
calcitonin, estrogen, and raloxifene, do not impede endochondral fracture healing
but may delay repair due to impaired remodeling. Although bisphosphonates and
denosumab delay callus remodeling, they increase callus volume and result in
unaltered biomechanical properties. Calcitonin increases cartilage formation and
callus maturation, resulting in improved biomechanical properties. Parathyroid
hormone, an anabolic agent, has demonstrated promise in animal models, resulting
in accelerated healing with increased callus volume and density, more rapid
remodeling to mature bone, and improved biomechanical properties. Clinical data
with parathyroid hormone have demonstrated enhanced healing in distal radius and
pelvic fractures as well as postoperatively following spine surgery. Strontium
ranelate, which may have both antiresorptive and anabolic properties, affects
fracture healing differently in normal and osteoporotic bone. While there is no
effect in normal bone, in osteoporotic bone, strontium ranelate increases callus
bone formation, maturity, and mineralization; forms greater and denser
trabeculae; and improves biomechanical properties. Further clinical studies with
these medications are needed to fully understand their effects on fracture
healing in order to simultaneously treat fragility fractures and underlying
osteoporosis.
PMID- 26419478
TI - TNF-alpha: a treatment target or cause of sarcoidosis?
AB - Sarcoidosis is a systemic granulomatous disease that affects numerous organs,
commonly manifesting at the lungs and skin. While corticosteroids remain the
first line of treatment, tumour necrosis factor alpha (TNF-alpha) inhibitors have
been investigated as one potential steroid sparing treatment for sarcoidosis. TNF
alpha is one of many components involved in the formation of granulomas in
sarcoidosis. While there have been larger scale studies of biologic TNF-alpha
inhibition in systemic sarcoidosis, studies in cutaneous disease are limited.
Paradoxically, in some patients treated with biologic TNF-alpha inhibitors for
other diseases, treatment can induce the development of sarcoidosis. In the light
of this complexity, we discuss the role of TNF-alpha in granuloma formation, the
therapeutic role of TNF-alpha inhibition and immunologic abnormalities following
treatment with these TNF-alpha inhibitors including drug-specific alterations
involving interferon-gamma, lymphotoxin-alpha, TNF receptor 2 (TNFR2) and T
regulatory cells.
PMID- 26419479
TI - Cross-dehydrogenative coupling of alpha-C(sp(3))-H of ethers/alkanes with
C(sp(2))-H of heteroarenes under metal-free conditions.
AB - Here we have developed an effective metal-free dehydrogenative coupling method
wherein alpha-oxyalkyl and alkyl radicals were generated from various ethers and
alkanes to undergo coupling with a variety of electron-deficient heteroarenes
such as un/substituted iso-quinolones, quinolines, pyridines, pyrazines and
pyrimidines. The persulfate-acetone-water system was optimized for the
dehydrogenative coupling with cyclic ethers which gave moderate to excellent
yields of alpha-oxyalkyl containing heteroarenes. We have also optimized the
conditions for coupling with cyclic alkanes and alicyclic ethers and demonstrated
by conducting the reactions with a variety of electron-deficient heteroarenes.
Further, the present method is also applicable to electron deficient arenes like
naphthoquinones and moreover, it didn't require any external acid.
PMID- 26419480
TI - Forensic uses of research biobanks: should donors be informed?
AB - Occasional reports in the literature suggest that biological samples collected
and stored for scientific research are sometimes accessed and used for a variety
of forensic purposes. However, donors are almost never informed about this
possibility. In this paper we argue that the possibility of forensic access may
constitute a relevant consideration at least to some potential research subjects
in deciding whether to participate in research. We make the suggestion that if
some type of forensic access to research collections is likely to be perceived by
the subjects as a reason against donating their biological materials, there are
good ethical reasons to make this type of access impossible or at least severely
restricted. We also provide an ethical argument for the claim that, if a total
ban on this type of forensic access cannot be achieved, potential research
subjects should be informed about the extent to which this type of forensic
access is possible.
PMID- 26419481
TI - [Patients' need for consultation after a geriatric assessment in family practice
: Survey].
AB - BACKGROUND: During a doctor-patient consultation patients usually seek
information by disclosing their reasons for requesting the encounter. Geriatric
assessment allows a proactive examination of patients' overall health and
function and provides an opportunity to broach issues beyond the initial purposes
of the consultation. OBJECTIVES: The study aimed at investigating older patients'
information seeking behavior following a geriatric assessment and the kind of
topics they wished to discuss, taking a variety of patient and health-related
factors into account. MATERIAL AND METHODS: A total of 317 patients (>= 70 years)
underwent a geriatric assessment in 40 general practices. Subsequently they
obtained a list of the problems uncovered and rated the relevance and information
needs for each problem. Analyses consisted of determining the prevalence of
information need for each health topic and identifying predictors in a mixed
model (multilevel regression analysis). RESULTS: The 317 patients presented with
a median of 11 health problems (interquartile range, IQR 8-14) and 80 % of the
patients had information needs concerning only a few of the problems. High
information needs were present for physical complaints and for vaccination
issues. Little information seeking behavior was evident for unhealthy lifestyles,
falls, limitations in daily activities and psychosocial problems. In the mixed
model the personal relevance and the type of health problem both had a
significant and independent effect on information seeking behavior. CONCLUSION: A
geriatric assessment generates a moderate need for information. It provides
physicians with an opportunity to focus on those health problems that are
important to older patients but not usually addressed in normal consultations.
This particularly applies to limitations in daily activities and psychosocial
problems.
PMID- 26419482
TI - Outcome after operative treatment of proximal humeral fractures in elderly
patients.
AB - BACKGROUND: The proximal humeral fracture (PHF) (5 %) of the elderly is the third
most common fracture after proximal femoral and distal radius fractures. Proximal
femoral fractures often lead to a loss of autonomy. OBJECTIVES: The aim of this
study is to show how PHF changes the patient's autonomy and the coping with
everyday life as well as which factors influence the outcome 1 year (y) after
surgery. MATERIALS AND METHODS: Data of 62 patients with surgical treatment of a
PHF >= 60 y was prospectively collected. With a telephone interview Short Form
(SF) 12 (physical and mental health; PH, MH), Barthel Index (BI), range of
motion, pain, and satisfaction was observed after 3 and 12 months. The dependence
of outcome on different factors was investigated. RESULTS: The mean age was 73.3
y (median 73, 60-94). Mortality after 3 months was 3 % and after 1 y 11 %. The PH
before the injury (47.9) was significantly better than after 3 months (37.1) and
after 1 y (42.6). The MH showed no difference. The BI before the injury (92) was
significantly better than after 3 months (86), but the same after 1 y (91). After
1 y > 50 % were able to abduct and flex the arm > 90 degrees . More than two
thirds were able to perform everyday life activities for body care and nutrition
after 1 y. Approximately, 73 % of the patients had little or no pain, and 84 %
were satisfied with the result after 1 y. Good score values before the fracture
resulted in better outcome. Higher severity in fracture led to a higher level of
pain. DISCUSSION: A surgically treated PHF in the elderly does not lead to a
relevant impairment in quality of life. Despite the lack of complete retrieval of
range of motion patients achieve a good to very good result in coping with
everyday life.
PMID- 26419483
TI - Noninvasive Tuberculosis Screening in Free-Living Primate Populations in Gombe
National Park, Tanzania.
AB - Recent advances in noninvasive detection methods for mycobacterial infection in
primates create new opportunities for exploring the epidemiology of tuberculosis
in free-living species. Chimpanzees (Pan troglodytes schweinfurthii) and baboons
(Papio anubis) in Gombe National Park, Tanzania, were screened for infection with
pathogens of the Mycobacterium tuberculosis Complex using Fecal IS6110 PCR; none
was positive. This study demonstrates the feasibility of large-scale
mycobacterial screening in wild primates.
PMID- 26419484
TI - [Blood exposure accidents: knowledge and practices of hospital health workers in
Mali].
AB - This is a prospective study conducted in December 2012 among 128 at the
Nianankoro Fomba Hospital in Segou in order to assess their knowledge and
practices on Blood Exposure Accidents (BEA). The average age of caregivers was
35.4 +/- 9 years (range: 22-59 years). The nurses were predominant with 37.5%.
The definition of BEA was mastered by 43.8%. The main transmissible infectious
agents (HIV, HBV and HCV) were ignored by 76.6%. Questioning revealed that during
the treatment, 78.9% wore gloves and 36.0% recapped needles after use. The
concept of washing and disinfection after BEA was known by 68.8%. The
disinfectant applied was correct for 21.9% of the cases, the time of application
for 69.5%. Consulting a referring physician after BEA was mandatory for 32% of
them. The time limit of 48 hours delay for the declaration of BEA was experienced
by 51.3%. Among staff interviewed 82 caregivers (64.1%) experienced at least one
BEA. Students and nursing students were most at risk. Needle pricks were the most
frequent (73.2%). BEA is a major problem in the Segou Nianankoro Fomba Hospital.
Compliance with standard precautions is not of common practice. Post-exposure
care is not widely known. The experienced cases show poor management of BEA in
the structure.
PMID- 26419485
TI - First reported case of intraocular Gnathostoma spinigerum in Cambodia.
AB - A live intraocular nematode was identified from a 37 year-old man presented with
iritis, pain, redness, lacrimation, swelling, vision loss and intermittent
blindness during many hours per day of the left eye. By using slit lamp
examination, a worm was removed from iris in an ophthalmology outpatient
department setting and sent to the Medical Microbiology Laboratory, Institut
Pasteur du Cambodge. Gnathostoma spinigerum was identified, based on its typical
morphology via microscopic examination. Based on our diagnosis, the patient was
treated by oral albendazole and responded well to this therapy.
PMID- 26419486
TI - [Anopheles gambiae, major malaria vector in Logbessou, a peri-urban area of
Douala (Cameroon)].
AB - An entomological survey was carried out from August to November 2013, in order to
determine the vector system of a building site for social housing in a coastal
periurban district of Douala (Cameroon). Mosquito larvae were collected and adult
endophilic mosquitoes captured on volunteers, for a total sample of 4897
mosquitoes. Morpho-taxonomic techniques alongside molecular techniques enabled
the identification of 4 species, all aggressive to humans: Cx. pipiens (22.3%),
Ae. albopictus (0.3%), An. coluzzii and An. gambiae (77.4%). The overall average
biting rate recorded was 41.73 bites/person/night (b/p/n). An. gambiae s.l.
represents 90.82% of this aggressive fauna, followed by Cx. pipiens (8.58%) and
Ae. albopictus (0.6%). The detection of CSP showed that An. gambiae was
responsible for 100% of P. falciparum transmission. The overall mean
Entomological Inoculation Rate (EIR) was 3.94 ib/p/n. Female An. gambiae
mortality rates were 14.47%, 82.5% and 100% respectively with DDT, permethrin and
deltamethrin. The proliferation of An. gambiae in this area during raining
season, at the detriment of An. coluzzii Coetze & Wilkerson and An. melas
Theobald known to be major malaria vectors in island and coastal areas of Africa,
may owe to the forest that still colonises this coastal peri-urban locality.
Residents should therefore make use of deltamethrin based protective measures.
PMID- 26419488
TI - The cis-Diammineplatinum(II) Complex of Curcumin: A Dual Action DNA Crosslinking
and Photochemotherapeutic Agent.
AB - [Pt(cur)(NH3)2](NO3) (1), a curcumin-bound cis-diammineplatinum(II) complex,
nicknamed Platicur, as a novel photoactivated chemotherapeutic agent releases
photoactive curcumin and an active platinum(II) species upon irradiation with
visible light. The hydrolytic instability of free curcumin reduces upon binding
to platinum(II). Interactions of 1 with 5'-GMP and ct-DNA indicated formation of
platinum-bound DNA adducts upon exposure to visible light (lambda=400-700 nm). It
showed apoptotic photocytotoxicity in cancer cells (IC50 ~ 15 MUM), thus forming
(?)OH, while remaining passive in the darkness (IC50 >200 MUM). A comet assay and
platinum estimation suggest Pt-DNA crosslink formation. The fluorescence
microscopic images showed cytosolic localization of curcumin, thus implying
possibility of dual action as a chemo- and phototherapeutic agent.
PMID- 26419487
TI - The effect of pregabalin and celecoxib on the analgesic requirements after
laparoscopic cholecystectomy: a randomized controlled trial.
AB - PURPOSE: Early postoperative pain is a common complaint after elective
laparoscopic cholecystectomy. The use of non-opioid medications as a part of
multimodal analgesia has been increasingly advocated in the management of acute
post-surgical pain. This randomized, double-blinded, placebo-controlled study
evaluated the efficacy of pregabalin, celecoxib, and their combination in the
management of acute postoperative pain in patients undergoing elective
laparoscopic cholecystectomy. METHODS: One hundred ASA I/II patients scheduled to
undergo elective laparoscopic cholecystectomy were assigned to receive two
perioperative doses, 12 h apart, of either pregabalin alone, celecoxib alone,
their combination, or a placebo. Standard anesthetic protocol was followed. The
primary outcomes were postoperative pain at rest and with movement. Secondary
outcomes were fentanyl requirements and side effects, which were assessed at 1,
2, 4, 8, 12, and 24 h following surgery. Patient satisfaction with pain relief
was recorded at discharge. Differences in main outcomes were analyzed using an
intention-to-treat approach. RESULTS: There was no statistically significant
difference (p > 0.05) between the four groups in terms of outcomes such as rest
pain, movement pain, postoperative fentanyl requirements, or changes in anxiety
scores. Patients who had only celecoxib had significantly higher satisfaction
with pain management (p = 0.013). Patients who had only pregabalin were at three
times-higher odds of having drowsiness (p = 0.040) and four-times-higher odds of
having lightheadedness (p = 0.019) when compared with the placebo group.
CONCLUSIONS: Pregabalin, celecoxib alone, or in combination offers no analgesic
superiority over standard opioid care in the treatment of postoperative pain
following laparoscopic cholecystectomy.
PMID- 26419489
TI - Deciphering mechanisms of malathion toxicity under pulse exposure of the
freshwater cladoceran Daphnia magna.
AB - The organophosphate pesticide (OP) malathion is highly toxic to freshwater
invertebrates, including the cladoceran Daphnia magna, a widely used test
organism in ecotoxicology. To assess whether toxic effects of malathion are
driven primarily by exposure concentration or exposure duration, D. magna was
pulse exposed to equivalent integrated doses (duration * concentration): 3 h * 16
MUg/L, 24 h * 2 MUg/L, and 48 h * 1 MUg/L. After recovery periods of 3 h, 24 h,
and 48 h, the toxicity of malathion on different biological levels in D. magna
was examined by analyzing the following endpoints: survival and immobilization;
enzyme activities of acetylcholinesterase (AChE), carboxylesterase (CbE), and
glutathione S-transferase (GST); and AChE gene expression. The results showed no
difference in survival among equivalent integrated doses. Adverse sublethal
effects were driven by exposure concentration rather than pulse duration.
Specifically, short pulse exposure to a high concentration of malathion resulted
in more immobilized daphnids, lower AChE and CbE activities, and a higher
transcript level of AChE gene compared with long pulse exposure to low
concentration. The expression of the AChE gene was up-regulated, indicating a
compensatory mechanism to cope with enzyme inhibition. The study shows the need
for obtaining a better understanding of the processes underlying toxicity under
realistic exposure scenarios, so this can be taken into account in environmental
risk assessment of pesticides.
PMID- 26419490
TI - First magenetic resonance imaging studies on aluminium maltolate-treated aged New
Zealand rabbits: an Alzheimer's animal model.
AB - BACKGROUND: Alzheimer's disease is a devastative neurodegenerative disorder. To
date, there has been no animal model that could unravel the complete disease
pathology. Magnetic resonance imaging has played a pivotal role in the
quantitative assessment of brain tissue atrophy for a few decades. In particular,
temporal lobe atrophy and ventricular dilatation have been found to be sensitive
in Alzheimer's disease. METHODS: The present study focused on the replication of
these crucial pathological events to enable disease progression to be diagnosed
at an early stage and stopped through the use of potential therapeutic
strategies. RESULT: The objective of this study was to show temporal lobe atrophy
and ventricular dilatation in aluminium maltolate-treated aged New Zealand
rabbit, and our study was able to demonstrate this for the first time.
CONCLUSION: The present study makes this animal model a substantial one for
further molecular level studies and opens up new targets for potential
therapeutic strategies.
PMID- 26419491
TI - Mindfulness-based stress reduction for long-term physical conditions: A
systematic review.
AB - OBJECTIVE: To identify whether mindfulness-based stress reduction is effective in
improving physical health outcomes for long-term physical conditions. METHOD: A
systematic review of the literature (retrieved from MEDLINE, PubMed and
PsycINFO). RESULTS: Fifteen studies were included in the review. None of the
studies assessed as having a low risk of bias demonstrated significant
improvements in physical health status although there was some emerging evidence
that mindfulness-based stress reduction may be useful in pain conditions. There
was some preliminary evidence that it may also be effective in improving primary
insomnia and irritable bowel syndrome. Small to moderate effect sizes were also
found for asthma, pain, tinnitus, fibromyalgia and somatization disorders.
CONCLUSION: Although there is some preliminary support for the use of mindfulness
based stress reduction in physical health conditions, further research is
required before it could be considered an effective intervention for improving
physical health outcomes.
PMID- 26419492
TI - Developing a Workflow Composite Score to Measure Clinical Information Logistics.
A Top-down Approach.
AB - BACKGROUND: Availability and usage of individual IT applications have been
studied intensively in the past years. Recently, IT support of clinical processes
is attaining increasing attention. The underlying construct that describes the IT
support of clinical workflows is clinical information logistics. This construct
needs to be better understood, operationalised and measured. OBJECTIVES: It is
therefore the aim of this study to propose and develop a workflow composite score
(WCS) for measuring clinical information logistics and to examine its quality
based on reliability and validity analyses. METHODS: We largely followed the
procedural model of MacKenzie and colleagues (2011) for defining and
conceptualising the construct domain, for developing the measurement instrument,
assessing the content validity, pretesting the instrument, specifying the model,
capturing the data and computing the WCS and testing the reliability and
validity. RESULTS: Clinical information logistics was decomposed into the
descriptors data and information, function, integration and distribution, which
embraced the framework validated by an analysis of the international literature.
This framework was refined selecting representative clinical processes. We chose
ward rounds, pre- and post-surgery processes and discharge as sample processes
that served as concrete instances for the measurements. They are sufficiently
complex, represent core clinical processes and involve different professions,
departments and settings. The score was computed on the basis of data from 183
hospitals of different size, ownership, location and teaching status. Testing the
reliability and validity yielded encouraging results: the reliability was high
with r(split-half) = 0.89, the WCS discriminated between groups; the WCS
correlated significantly and moderately with two EHR models and the WCS received
good evaluation results by a sample of chief information officers (n = 67). These
findings suggest the further utilisation of the WCS. CONCLUSION: As the WCS does
not assume ideal workflows as a gold standard but measures IT support of clinical
workflows according to validated descriptors a high portability of the WCS to
other hospitals in other countries is very likely. The WCS will contribute to a
better understanding of the construct clinical information logistics.
PMID- 26419493
TI - Tangential cell migration during layer formation of chick optic tectum.
AB - The laminated structure of the optic tectum is formed by radial and tangential
cell migration during development. Studies of developing chick optic tectum have
revealed two streams of tangential cell migration in the middle and superficial
layers, which have distinctive origins, migratory paths, modes of migration, and
destinations. We will review the process of the two types of tangential
migrations, in order to elucidate their roles in the formation of the optic
tectum layers.
PMID- 26419494
TI - Civilian deaths from weapons used in the Syrian conflict.
PMID- 26419495
TI - 'When operating a cafeteria, sales come before nutrition' - finding barriers and
facilitators to serving reduced-sodium meals in worksite cafeterias.
AB - OBJECTIVE: The present study was conducted to examine barriers to and
facilitators of serving reduced-sodium meals (RSM) in worksite cafeterias.
DESIGN: We conducted in-depth interviews with key stakeholders in food catering
companies. SETTING: Food catering companies at various customer sites in South
Korea. SUBJECTS: A total of nineteen interviews with twenty-five participants
from ten catering companies were conducted. Sixteen on-site dietitians and nine
managers from the catering companies' headquarters participated in the
interviews. RESULTS: Four main themes emerged from the interviews. First, key
stakeholders' psychosocial characteristics (perception, intention and knowledge)
are important in serving RSM in worksite cafeterias. Second, skills and
techniques related to measuring sodium content and preparing RSM were emphasized
by the interviewees. Third, the lack of various delicious low-sodium menus is a
barrier to serving RSM. Lastly, a number of environmental factors were addressed,
which include social support for reduced-sodium diets (a facilitator) and
pressure to maintain profit margins (a barrier), that contribute to serving meals
with less salt. Based on these factors, various recommendations for future sodium
reduction policies and programmes were suggested. CONCLUSIONS: It is important to
implement population-wide sodium reduction as a means of preventing CVD and
stroke. The study provided important facilitators of and barriers to serving RSM
in worksite cafeterias, which could be helpful in developing environmental
interventions that promote low-sodium diets.
PMID- 26419496
TI - Adolescence as a Sensitive Period of Brain Development.
AB - Most research on sensitive periods has focussed on early sensory, motor, and
language development, but it has recently been suggested that adolescence might
represent a second 'window of opportunity' in brain development. Here, we explore
three candidate areas of development that are proposed to undergo sensitive
periods in adolescence: memory, the effects of social stress, and drug use. We
describe rodent studies, neuroimaging, and large-scale behavioural studies in
humans that have yielded data that are consistent with heightened neuroplasticity
in adolescence. Critically however, concrete evidence for sensitive periods in
adolescence is mostly lacking. To provide conclusive evidence, experimental
studies are needed that directly manipulate environmental input and compare
effects in child, adolescent, and adult groups.
PMID- 26419497
TI - Povidone-iodine pleurodesis for congenital chylothorax of the newborn.
PMID- 26419498
TI - Optimal visualization of the fetal four-chamber and outflow tract views with
transabdominal ultrasound in the morbidly obese: Are we there yet?
AB - BACKGROUND: To compare optimal visualization of the four-chamber and outflow
tract views of the fetal heart on sonographic examination between morbidly obese
(body mass index [BMI] >= 40 kg/m(2) ) and nonobese (BMI < 25 kg/m(2) ) pregnant
women. METHODS: In this retrospective cohort study, we included records and
images from 509 pregnant women who had first undergone sonographic examination
between 18 and 36 weeks' fetal gestational age. RESULTS: Compared with the
nonobese women, morbidly obese women had lower optimal visualization of the four
chamber and outflow-tract heart views: four-chamber view, morbidly obese, 83/186
(44.6%), versus nonobese, 283/323 (87.6%), and outflow-tract view, morbidly
obese, 80/186 (43%) versus nonobese, 258/290 (89%); p < 0.0001 for each
comparison. Similar outcomes were observed when the results from each subcategory
of morbidly obese women (ie, BMI 40-49.9, 50-59.9, and >=60 kg/m(2) ) were
compared with that from nonobese women; p < 0.0001 for each comparison. These
outcomes remained the same regardless of whether this comparison was made among
those who had their examination before or at 19 weeks' or more gestational age.
Among the morbidly obese women, there was no difference in optimal visualization
of the four-chamber or outflow-tract views regardless of whether the examination
was performed at <23 weeks' or at >=23 weeks' gestational age: four-chamber view
<23 weeks, 44.8% (78/174), versus four-chamber view >=23 weeks, 41.7% (5/12); p =
0.8, and outflow-tract view <23 weeks, 43.1% (75/174), versus outflow-tract view
>=23 weeks, 41.7% (5/12); p = 0.9. After controlling for maternal age and race,
the odds of visualizing the four-chamber and outflow-tract views in the morbidly
obese were reduced compared with those in their nonobese counterparts: odds ratio
(OR) for four-chamber, 0.13; 95% confidence interval (CI), 0.08-0.21, and OR for
outflow-tract, 0.11; 95% CI, 0.07-0.17. CONCLUSIONS: Optimal visualization of the
fetal four-chamber and outflow-tract views was achieved in less than 50% of
morbidly obese women, compared with almost 90% in nonobese women.
PMID- 26419499
TI - Effect of birth ball on labor pain relief: A systematic review and meta-analysis.
AB - AIM: To critically evaluate the available evidence related to the impact of using
a birth ball on labor pain relief. METHODS: The Cochrane library, Cochrane
Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed and Scopus were
searched from their inception to January 2015 using keywords: (Birth* OR Swiss OR
Swedish OR balance OR fitness OR gym* OR Pezzi OR sport* OR stability) AND
(ball*) AND (labor OR labour OR Obstetric). All available randomized controlled
trials involving women using a birth ball for pain relief during labor were
considered. The search resulted in 341 titles and abstracts, which were narrowed
down to eight potentially relevant articles. Of these, four studies met the
inclusion criteria. Pain intensity on a 10 cm visual analogue scale was used as
the main outcome measure. Risk of bias was assessed using the Cochrane Risk of
Bias tool. Comprehensive Meta-Analysis Version 2 was used for statistical
analysis. RESULTS: Four RCTs involving 220 women were included in the systematic
review. One study was excluded from the meta-analysis because of heterogeneous
interventions and a lack of mean and standard deviation results of labor pain
score. The meta-analysis showed that birth ball exercises provided statistically
significant improvements to labor pain (pooled mean difference -0.921; 95%
confidence interval -1.28, -0.56; P = 0.0000005; I(2) = 33.7%). CONCLUSION: The
clinical implementation of a birth ball exercise could be an effective tool for
parturient women to reduce labor pain. However, rigorous RCTs are needed to
evaluate the effect of the birth ball on labor pain relief.
PMID- 26419500
TI - Long-term survival in microcephalic osteodysplastic primordial dwarfism type I:
Evaluation of an 18-year-old male with g.55G>A homozygous mutation in RNU4ATAC.
PMID- 26419501
TI - Demographic and psychosocial correlates of sexual activity in older Chinese
people.
AB - AIMS AND OBJECTIVES: This study examines sexual activity and associated
psychosocial factors in older Chinese people. BACKGROUND: Sexuality continues to
play a pivotal role in our lives even as we grow old. There is, however, very
limited research on the topic in older populations. DESIGN: Cross-sectional
survey. METHODS: A representative sample of 688 older Chinese people (>60 years
old) were individually interviewed on their demographic characteristics; their
interest in, knowledge of and perceived control over sexual activities; and their
engagement in sexual activity. RESULTS: The results show that 51.32% of men and
41.26% of women reported engaging in some form of sexual activity. Sexual
intercourse and caressing were commonly reported. A multiple regression analysis
also showed that a higher level of sexual activity was associated with being
younger, living with a spouse, having a strong interest in sex, having sufficient
knowledge of elder sexuality and a high perceived control over sex. Distinct
predictive factors in each gender were observed. A high level of perceived
control was associated with a higher level of sexual activity in males but not
females. A series of binary logistic regression analyses were conducted to
determine the demographic and psychosocial correlates of sexual activity. With
the exception of the use of objects (sex toys), sexual activities were
consistently associated with being younger; living with a spouse; and having high
levels of interest, knowledge and perceived control. CONCLUSIONS: A sizable
amount of older Chinese people engage in varying degrees of sexual activity, and
most are still interested in sex. RELEVANCE TO CLINICAL PRACTICE: Frontline
health professionals need to be aware of the growing needs for sex education in
older persons, particular attention should be paid to discuss the limitations
brought about by various chronic conditions associated with ageing and their
relevance to elder sexuality.
PMID- 26419502
TI - Thermocrinis jamiesonii sp. nov., a thiosulfate-oxidizing, autotropic thermophile
isolated from a geothermal spring.
AB - An obligately thermophilic, chemolithotrophic, microaerophilic bacterium,
designated strain GBS1T, was isolated from the water column of Great Boiling
Spring, Nevada, USA. Thiosulfate was required for growth. Although capable of
autotrophy, growth of GBS1T was enhanced in the presence of acetate, peptone or
Casamino acids. Growth occurred at 70-85 degrees C with an optimum at 80
degrees C, at pH 6.50-7.75 with an optimum at pH 7.25, with 0.5-8 % oxygen with
an optimum at 1-2 % and with <= 200 mM NaCl. The doubling time under optimal
growth conditions was 1.3 h, with a final mean cell density of 6.2 +/- 0.5 * 107
cells ml- 1. Non-motile, rod-shaped cells 1.4-2.4 * 0.4-0.6 MUm in size occurred
singly or in pairs. The major cellular fatty acids (>5 % of the total) were C20 :
1omega9c, C18 : 0, C16 : 0 and C20 : 0. Phylogenetic analysis of the GBS1T 16S
rRNA gene sequence indicated an affiliation with Thermocrinis ruber and other
species of the genus Thermocrinis, but determination of 16S rRNA gene sequence
similarity ( <= 97.10 %) and in silico estimated DNA-DNA hybridization values (
<= 18.4 %) with the type strains of recognized Thermocrinis species indicate that
the novel strain is distinct from described species. Based on phenotypic,
genotypic and phylogenetic characteristics, a novel species, Thermocrinis
jamiesonii sp. nov., is proposed, with GBS1T ( = JCM 19133T = DSM 27162T) as the
type strain.
PMID- 26419503
TI - Effects of dietary lysozyme levels on growth performance, intestinal morphology,
non-specific immunity and mRNA expression in weanling piglets.
AB - The aim of the present study was to determine the effect of dietary lysozyme
levels on growth performance, gut health and non-specific immunity of weanling
piglets. A total of 150 weanling piglets were allocated to six treatments. The
piglets were fed the same basel diet supplemented with 0, 30, 60, 90 and 120
mg/kg lysozyme as well as antibiotics for 28 days. From day 14 to day 28 of
dietary treatment, piglets fed 90 mg/kg lysozyme had greater average daily gain
than piglets fed control diet. During the whole experimental period, piglets fed
120 mg/kg lysozyme tended to have greater average daily gain than piglets fed
control diet. Compared with piglets fed control diet, piglets fed diets
containing antibiotics and 90 mg/kg lysozyme had greater villus height to crypt
depth ratio in duodenum and jejunum. Additionally, dietary supplementation of 60
and 90 mg/kg lysozyme as well as antibiotics enhanced the phagocytic activity of
peritoneal macrophages in piglets. In conclusion, dietary lysozyme can accelerate
the growth of weanling piglets by improving gut health and non-specific immunity
and supplementing 90 mg/kg lysozyme is as effective as antibiotics (20 mg/kg
colistin sulphate + 50 mg/kg kitasamycin) in improving the growth performance of
weanling piglets.
PMID- 26419504
TI - Use of a small particle solid-core packing for improved efficiency and rapid
measurement of sirolimus and everolimus by LC-MS/MS.
AB - Measurement of whole blood sirolimus and everolimus is required in order to
optimize patient treatment following solid organ transplant. Assay by LC-MS/MS is
increasingly preferred; however efficient use of the instrument and short
turnaround times are crucial. Use of a 1.6 um solid-core packing HPLC column
(Cortecs) gave significant increases in efficiency, sensitivity and throughput
compared with an existing method, following simple protein precipitation of small
volume (20 MUL) whole blood samples. Sirolimus, everolimus and the stable
isotopic internal standard ((13) C2 D4 - everolimus) eluted at around 0.8 min,
and total analytical run time was 2.2 min, saving almost 4 min per sample
compared with an existing method. Within-assay imprecision (CV) was 3.3-8.5%, and
between-assay imprecision was 2.2-10.8%. Retrospective assay of external quality
assurance samples and comparison of patient samples assayed in parallel showed
only small differences (between +6.8 and -1.9%) in results using the Cortecs
column when compared with the existing method. No significant interferences or
ion suppression were observed. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26419505
TI - In vivo quantification of hyperoxic arterial blood water T1.
AB - Normocapnic hyperoxic and hypercapnic hyperoxic gas challenges are increasingly
being used in cerebrovascular reactivity (CVR) and calibrated functional MRI
experiments. The longitudinal arterial blood water relaxation time (T1a) change
with hyperoxia will influence signal quantification through mechanisms relating
to elevated partial pressure of plasma-dissolved O2 (pO2) and increased oxygen
bound to hemoglobin in arteries (Ya) and veins (Yv). The dependence of T1a on Ya
and Yv has been elegantly characterized ex vivo; however, the combined influence
of pO2, Ya and Yv on T1a in vivo under normal ventilation has not been reported.
Here, T1a is calculated during hyperoxia in vivo by a heuristic approach that
evaluates T1 -dependent arterial spin labeling (ASL) signal changes to varying
gas stimuli. Healthy volunteers (n = 14; age, 31.5 +/- 7.2 years) were scanned
using pseudo-continuous ASL in combination with room air (RA; 21% O2/79% N2),
hypercapnic normoxic (HN; 5% CO2/21% O2/74% N2) and hypercapnic hyperoxic (HH; 5%
CO2/95% O2) gas administration. HH T1a was calculated by requiring that the HN
and HH cerebral blood flow (CBF) change be identical. The HH protocol was then
repeated in patients (n = 10; age, 61.4 +/- 13.3 years) with intracranial
stenosis to assess whether an HH T1a decrease prohibited ASL from being performed
in subjects with known delayed blood arrival times. Arterial blood T1a decreased
from 1.65 s at baseline to 1.49 +/- 0.07 s during HH. In patients, CBF values in
the affected flow territory for the HH condition were increased relative to
baseline CBF values and were within the physiological range (RA CBF = 36.6 +/-
8.2 mL/100 g/min; HH CBF = 45.2 +/- 13.9 mL/100 g/min). It can be concluded that
hyperoxic (95% O2) 3-T arterial blood T1aHH = 1.49 +/- 0.07 s relative to a
normoxic T1a of 1.65 s.
PMID- 26419506
TI - Do CHA2 DS2 VASc and HAS-BLED scores influence 'real-world' anticoagulation
management in atrial fibrillation? 1556 patient registry from the reference
cardiology centre.
AB - INTRODUCTION: Although recommendations for the antithrombotic management of
atrial fibrillation (AF) are based on strong evidence, the European guidelines
are not fully implemented into practice. OBJECTIVES: The objective of this study
is to analyse antithrombotic treatment in AF in Poland after the publication of
the European Society of Cardiology Guidelines in 2012. PATIENTS AND METHODS: We
retrospectively studied 1556 patients with AF from the Reference Cardiology
University Centre in Poland in 2012-2014. RESULTS: CHA2 DS2 VASc and HAS-BLED
scores were 3.5 +/- 1.7 and 2.4 +/- 1.1. Anti-vitamin K agent were prescribed in
59%, with non-vitamin K antagonist oral anticoagulants in 12%, acetylsalicylic
acid (ASA) alone in 18%. Older patients (p < 0.0001) and with paroxysmal AF were
less likely to receive oral anticoagulation (OAC, p < 0.0001). The risk of stroke
according to CHA2 DS2 VASc score was higher in patients who did not receive OAC
(p < 0.0001). The use of OAC increased with increasing CHA2 DS2 VASc score but
was less frequent in score >= 4. The risk of bleeding was higher in patients
without OAC (p < 0.0001). The odds of non-vitamin K antagonist oral
anticoagulants use were lower for older patients, patients with ischaemic heart
disease, chronic heart failure, anaemia, HAS-BLED >= 3 and valvular AF. ASA was
given in 39% of the patients, especially in paroxysmal AF (p < 0.0001). The odds
of ASA alone were higher for older patients, with ischaemic heart disease and
history of myocardial infarction (p < 0.0001). The odds of use of ASA as the only
treatment were 5.5 times higher for HAS-BLED >= 3 (p < 0.0001). CONCLUSIONS:
Antithrombotic management in AF is well implemented in Polish conditions, but we
show the lack of pattern concerning who is being treated with OAC and ASA when it
comes to the risk of stroke and bleeding.
PMID- 26419507
TI - Doxorubicin-poly (ethylene glycol)-alendronate self-assembled micelles for
targeted therapy of bone metastatic cancer.
AB - In order to increase the therapeutic effect of doxorubicin (DOX) on bone
metastases, a multifunctional micelle was developed by combining pH-sensitive
characteristics with bone active targeting capacity. The DOX loaded micelle was
self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd
PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX
hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution
(PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In
addition, with the increase of incubation time, more red DOX fluorescence was
observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX
loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of
free DOX in 48 h. Furthermore, the in vivo image experimental results indicated
that a larger amount of DOX was accumulated in the bone metastatic tumor tissue
after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which
was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN
micelle effectively delayed the tumor growth, decreased the bone loss and reduced
the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In
conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone
metastatic tumor.
PMID- 26419508
TI - Activating somatic mutations outside the SH2-domain of STAT3 in LGL leukemia.
PMID- 26419510
TI - Pathogen infection drives patterns of nutrient resorption in citrus plants.
AB - Nutrient resorption processes in the plants infected by pathogen remain poorly
understood. Huanglongbing (HLB) is a destructive disease of citrus. HLB-pathogen
'Candidatus Liberibacter asiaticus' grows specifically in the phloem of hosts and
may cause problems in the plant vascular system after infection. Therefore, it
brings a great concern about the phloem nutrient transport and nutrient intra
cycling in HLB-affected plants. We investigated the effects of 'Ca. L. asiaticus'
infection on nitrogen (N) and phosphorus (P) concentrations and resorption in
different citrus species (i.e. Citrus reticulata, Citrus limon and Citrus
maxima). HLB-pathogen infection had distinctive impacts on nutrient resorption in
different species. P resorption efficiency substantially decreased in infected C.
reticulata plants relative to the healthy plants in summer, which may account for
the marked decrease in the average fruit yield. P resorption was more efficient
in infected C. limon plants than in the healthy plants. However, for C. maxima
plants, HLB had no significant effects on N:P ratio in live leaves and resorption
efficiency as well as on fruit yield. Keeping efficient internal nutrient cycling
can be a strategy of citrus species being tolerant to HLB.
PMID- 26419511
TI - Nanocatalysts Fabricated by a Dealloying Method.
AB - Two types of nanomaterials with different morphologies are described in this
article: nanoporous metals and titanate nanowires. Both materials are fabricated
by a dealloying method. In the former case, the catalytic properties of
nanoporous gold and palladium are exemplified by many chemical transformations.
The reactions proceed without any support, stabilizer, or ligands. The catalyst
can be easily recovered by a simple separation process and reused many times
without significant loss of catalytic activity. In the latter case, the
dealloying of Ti-Al alloy is described as a new fabrication method for producing
ultrafine titanate nanowires. This method does not require high-temperature
conditions, which is advantageous for the construction of fine structures. The
key to this process is achieving a fine dispersion of intermetallic TiAl3
nanocrystals in the Al matrix in the mother alloy. The resulting nanowires
exhibit remarkable Sr(2+) ion-exchange properties.
PMID- 26419509
TI - Osteolytic lesions, cytogenetic features and bone marrow levels of cytokines and
chemokines in multiple myeloma patients: Role of chemokine (C-C motif) ligand 20.
AB - The relationship between bone marrow (BM) cytokine and chemokine levels,
cytogenetic profiles and skeletal involvement in multiple myeloma (MM) patients
is not yet defined. This study investigated a cohort of 455 patients including
monoclonal gammopathy of uncertain significance (MGUS), smoldering MM and
symptomatic MM patients. Skeletal surveys, positron emission tomography
(PET)/computerized tomography (CT) and magnetic resonance imaging (MRI) were used
to identify myeloma bone disease. Significantly higher median BM levels of both C
C motif Ligand (CCL)3 and CCL20 were found in MM patients with radiographic
evidence of osteolytic lesions as compared with those without, and in all MM
patients with positive PET/CT scans. BM levels of CCL3, CCL20, Activin-A and
Dickkopf-1 (DKK-1) were significantly higher in patients with high bone disease
as compared with patients with low bone disease. Moreover, CCL20 BM levels were
significant predictors of osteolysis on X-rays by multivariate logistic analysis.
On the other hand, DKK-1 levels were related to the presence of MRI lesions
independently of the osteolysis at the X-rays. Our data define the relationship
between bone disease and the BM cytokine and chemokine patterns highlighting the
tight relationship between CCL20 BM levels and osteolysis in MM.
PMID- 26419512
TI - Protocatechuic acid ameliorates neurocognitive functions impairment induced by
chronic intermittent hypoxia.
AB - Chronic intermittent hypoxia (CIH) is a serious consequence of obstructive sleep
apnoea (OSA) and has deleterious effects on central neurons and neurocognitive
functions. This study examined if protocatechuic acid (PCA) could improve
learning and memory functions of rats exposed to CIH conditions and explore
potential mechanisms. Neurocognitive functions were evaluated in male SD rats by
step-through passive avoidance test and Morris water maze assay following
exposure to CIH or room air conditions. Ultrastructure changes were investigated
with transmission electron microscopy, and neuron apoptosis was confirmed by
TUNEL assays. Ultrastructure changes were investigated with transmission electron
microscope and neuron apoptosis was confirmed by TUNEL assays. The effects of PCA
on oxidative stress, apoptosis, and brain IL-1beta levels were investigated.
Expression of Bcl-2, Bax, Cleaved Caspase-3, c-fos, SYN, BDNF and pro-BDNF were
also studied along with JNK, P38 and ERK phosphorylation to elucidate the
molecular mechanisms of PCA action. PCA was seen to enhance learning and memory
ability, and alleviate oxidative stress, apoptosis and glial proliferation
following CIH exposure in rats. In addition, PCA administration also decreased
the level of IL-1beta in brain and increased the expression of BDNF and SYN. We
conclude that PCA administration will ameliorate CIH-induced cognitive
dysfunctions.
PMID- 26419513
TI - Quantifying the Electron Donor and Acceptor Abilities of the Ketimide Ligands in
M(N?C(t)Bu2)4 (M = V, Nb, Ta).
AB - Addition of 4 equiv of Li(N?C(t)Bu2) to VCl3 in THF, followed by addition of 0.5
equiv of I2, generates the homoleptic V(IV) ketimide complex, V(N?C(t)Bu2)4 (1),
in 42% yield. Similarly, reaction of 4 equiv of Li(N?C(t)Bu2) with NbCl4(THF)2 in
THF affords the homoleptic Nb(IV) ketimide complex, Nb(N?C(t)Bu2)4 (2), in 55%
yield. Seeking to extend the series to the tantalum congener, a new Ta(IV)
starting material, TaCl4(TMEDA) (3), was prepared via reduction of TaCl5 with
Et3SiH, followed by addition of TMEDA. Reaction of 3 with 4 equiv of
Li(N?C(t)Bu2) in THF results in the isolation of a Ta(V) ketimide complex,
Ta(Cl)(N?C(t)Bu2)4 (5), which can be isolated in 32% yield. Reaction of 5 with
Tl(OTf) yields Ta(OTf)(N?C(t)Bu2)4 (6) in 44% yield. Subsequent reduction of 6
with Cp*2Co in toluene generates the homoleptic Ta(IV) congener Ta(N?C(t)Bu2)4
(7), although the yields are poor. All three homoleptic group 5 ketimide
complexes exhibit squashed tetrahedral geometries in the solid state, as
determined by X-ray crystallography. This geometry leads to a d(x(2)-y(2))(1)
((2)B1 in D(2d)) ground state, as supported by DFT calculations. EPR
spectroscopic analysis of 1 and 2, performed at X- and Q-band frequencies (~9 and
35 GHz, respectively), further supports the (2)B1 ground-state assignment,
whereas comparison of 1, 2, and 7 with related group 5 tetra(aryl), tetra(amido),
and tetra(alkoxo) complexes shows a higher M-L covalency in the ketimide-metal
interaction. In addition, a ligand field analysis of 1 and 2 demonstrates that
the ketimide ligand is both a strong pi-donor and strong pi-acceptor, an unusual
combination found in very few organometallic ligands.
PMID- 26419514
TI - DNA Microenvironment Monitored by Controlling Redox Blinking.
AB - The rate of a bimolecular reaction between a fluorophore and a freely diffusing
molecule in the solvent depends on the accessibility of the fluorophore for
collision with the molecule. We previously reported that the observation of
blinking, caused by the formation of R6G in the excited triplet state ((3) R6G*)
and its quenching reaction with O2 , allowed us to monitor the DNA conformational
changes between a duplex and a hairpin. However, the small molecular size of O2
hampered sensitive monitoring of the microenvironment changes around R6G. In this
study, we control redox blinking by adding a reductant ascorbic acid 2-phosphate
(VcP), which converts (3) R6G* into the radical anion form R6G(.-) , and by
adding a bulky oxidant FeDTPA. The bimolecular electron-transfer rate between
R6G(.-) and bulky FeDTPA was more strongly affected by microenvironment changes
around R6G, compared with that between (3) R6G* and the smaller O2 . This allowed
us to monitor subtle DNA conformational changes caused by a single different
nucleotide.
PMID- 26419515
TI - Towards a table-top microscope for nanoscale magnetic imaging using picosecond
thermal gradients.
AB - Research advancement in magnetoelectronics is challenged by the lack of a table
top magnetic measurement technique with the simultaneous temporal and spatial
resolution necessary for characterizing magnetization dynamics in devices of
interest, such as magnetic memory and spin torque oscillators. Although magneto
optical microscopy provides superb temporal resolution, its spatial resolution is
fundamentally limited by optical diffraction. To address this challenge, we study
heat rather than light as a vehicle to stroboscopically transduce a local
magnetic moment into an electrical signal while retaining picosecond temporal
resolution. Using this concept, we demonstrate spatiotemporal magnetic microscopy
using the time-resolved anomalous Nernst effect (TRANE). Experimentally and with
supporting numerical calculations, we find that TRANE microscopy has temporal
resolution below 30 ps and spatial resolution determined by the area of thermal
excitation. Based on these findings, we suggest a route to exceed the limits
imposed by far-field optical diffraction.
PMID- 26419516
TI - Death due to coronary artery anomaly with coexistence of Chiari network.
AB - Coronary artery anomalies rarely detected in autopsy series and angiograms can be
a component of complex malformations, besides, can be also associated with sudden
cardiac death. Presented case was 22-year-old male, who had suddenly fainted
during a football match played on artificial turf, he was transferred into the
hospital, however had died during intensive care therapy. He had been evaluated
by local prosecutor, and sent to our center for autopsy. At autopsy, internal
macroscopic examination revealed absence of the right coronary artery. A total of
two coronary artery ostia were observed. One of them originated from the left
aortic sinus, and the other one stemmed from 8 mm above the sinotubular line.
Besides, Chiari network formation was seen in the right atrium. This case with
coronary artery anomaly associated with formation of Chiari network was discussed
from the perspective of forensic medicine in the light of the literature
information.
PMID- 26419517
TI - [Determination of body fluid based on analysis of nucleic acids].
AB - Recent methodological approaches of molecular genetics allow isolation of nucleic
acids (DNA and RNA) from negligible forensic samples. Analysis of these molecules
may be used not only for individual identification based on DNA profiling but
also for the detection of origin of the body fluid which (alone or in mixture
with other body fluids) forms the examined biological trace. Such an examination
can contribute to the evaluation of procedural, technical and tactical value of
the trace. Molecular genetic approaches discussed in the review offer new
possibilities in comparison with traditional spectrum of chemical, immunological
and spectroscopic tests especially with regard to the interpretation of mixtures
of biological fluids and to the confirmatory character of the tests. Approaches
based on reverse transcription of tissue specific mRNA and their subsequent
polymerase chain reaction (PCR) and fragmentation analysis are applicable on
samples containing minimal amounts of biological material. Methods for body fluid
discrimination based on examination of microRNA in samples provided so far
confusing results therefore further development in this field is needed. The
examination of tissue specific methylation of nucleotides in selected gene
sequences seems to represent a promising enrichment of the methodological
spectrum. The detection of DNA sequences of tissue related bacteria has been
established and it provides satisfactory results mainly in combination with above
mentioned methodological approaches.
PMID- 26419518
TI - Truncus arteriosus communis with survival to the age of 46 years: case report.
AB - Truncus arteriosus communis is an uncommon congenital cardiovascular malformation
characterized by a single arterial trunk that arises from the base of the heart
and gives rise to the coronary, pulmonary and systemic arteries. The prognosis in
truncus arteriosus is very poor without surgical correction. The median age at
death without surgery ranges from 2 weeks to 3 months, with 85 % mortality by age
1 year. The authors report the autopsy findings of a 46 year old man with truncus
arteriosus communis without surgical intervention who died at the hospital
shortly after admission.
PMID- 26419519
TI - A color test for the convenient identification of an ingested surface activating
agent.
AB - Color tests are easy, simple and inexpensive methods for the qualitative
identification of chemicals. A color test was applied to the stomach contents of
a forensic autopsy case. The result of the test, using bromophenol blue reagent,
indicated the ingestion of a commercial cleaning product containing a cationic
surface activating agent. Our findings suggest that forensic investigators should
consider the additives used in commercial chemical products, such as surface
activating agents, when determining the cause of death.
PMID- 26419520
TI - Problems with the junior doctors' contract: how did we get here?
PMID- 26419521
TI - Implementing systems medicine within healthcare.
AB - The cause of a complex disease cannot be pinpointed to a single origin; rather, a
highly complex network of many factors that interact on different levels over
time and space is disturbed. This complexity requires novel approaches to
diagnosis, treatment, and prevention. To foster the necessary shift to a pro
active systems medicine, proof-of-concept studies are needed. Here, we highlight
several systems approaches that have been shown to work within the field of
respiratory medicine, and we propose the next steps for broader implementation.
PMID- 26419522
TI - Host-parasite coevolution in populations of constant and variable size.
AB - BACKGROUND: The matching-allele and gene-for-gene models are widely used in
mathematical approaches that study the dynamics of host-parasite interactions.
Agrawal and Lively (Evolutionary Ecology Research 4:79-90, 2002) captured these
two models in a single framework and numerically explored the associated time
discrete dynamics of allele frequencies. RESULTS: Here, we present a detailed
analytical investigation of this unifying framework in continuous time and
provide a generalization. We extend the model to take into account changing
population sizes, which result from the antagonistic nature of the interaction
and follow the Lotka-Volterra equations. Under this extension, the population
dynamics become most complex as the model moves away from pure matching-allele
and becomes more gene-for-gene-like. While the population densities oscillate
with a single oscillation frequency in the pure matching-allele model, a second
oscillation frequency arises under gene-for-gene-like conditions. These
observations hold for general interaction parameters and allow to infer generic
patterns of the dynamics. CONCLUSION: Our results suggest that experimentally
inferred dynamical patterns of host-parasite coevolution should typically be much
more complex than the popular illustrations of Red Queen dynamics. A single
parasite that infects more than one host can substantially alter the cyclic
dynamics.
PMID- 26419523
TI - Deforestation, drainage network, indigenous status, and geographical differences
of malaria in the State of Amazonas.
AB - BACKGROUND: Malaria is a major public health problem worldwide. In Brazil, an
average of 420,000 cases of malaria have been reported annually in the last 12
years, of which 99.7 % occurred in the Amazon region. This study aimed to analyse
the distribution of malaria in the State of Amazonas and the influence of
indigenous malaria in this scenario, to evaluate the correlation between
incidence rates and socio-economic and environmental factors, and to evaluate the
performance of health surveillance services. METHODS: This ecological study used
secondary data obtained from the SIVEP-MALARIA malaria surveillance programme.
The relationship between demographic, socio-economic and environmental factors,
the performance of health surveillance services and the incidence of malaria in
Amazonas, a multiple linear regression model was used. RESULTS: The crude rate of
malaria in Amazonas was 4142.72 cases per 100,000 inhabitants between 2003 and
2012. The incidence rates for the indigenous and non-indigenous populations were
12,976.02 and 3749.82, respectively, with an indigenous population attributable
fraction of only 8 %. The results of the linear regression analysis indicated a
negative correlation between the two socio-economic indicators (municipal human
development index (MHDI) and poverty rate) and the incidence of malaria in the
period. With regard to the environmental indicators (average annual deforestation
rate and percentage of areas under the influence of watercourses), the
correlation with the incidence rate was positive. CONCLUSIONS: The findings
underscore the importance of implementing economic and social development
policies articulated with strategic actions of environmental protection and
health care for the population.
PMID- 26419524
TI - Mothers' decision-making during times of stress as a lone parent: a qualitative
study.
AB - INTRODUCTION: Little empirical evidence exists to identify the impact that a
partner's absence or presence has on the mother's decision-making and her
consequential help-seeking behaviour when her child is unwell. METHODS: This
study used a qualitative design in three phases using focus groups and interviews
to explore Army mothers' help-seeking behaviour as a lone parent when their child
was unwell during the out-of-hours period. Thirty-one parents from a British Army
garrison were interviewed. RESULTS: The findings demonstrated that Army life
created a combination of stressors for Army mothers, which altered their help
seeking behaviour when their child was unwell. When their partner was available,
mothers contacted health services as a last resort, once all other avenues had
been exhausted. However, in contrast, in their partners' absence, they were
contacted as a first resort. CONCLUSION: An algorithm was generated from the
findings, which illustrates the importance of ascertaining whether the mother is
alone at the time of the consultation. Increased emotional vulnerability
intensified the need for reassurance and affected a mother's decision-making
ability. Primary healthcare staff should ascertain whether mothers are currently
lone parents at an early stage of their assessment, as this may influence the
entire consultation.
PMID- 26419525
TI - Gestation under chronic constant light leads to extensive gene expression changes
in the fetal rat liver.
AB - Recent reports account for altered metabolism in adult offspring from pregnancy
subjected to abnormal photoperiod, suggesting fetal programming of liver
physiology. To generate a pipeline of subsequent mechanistic experiments
addressing strong candidate genes, here we investigated the effects of constant
gestational light on the fetal liver transcriptome. At 10 days of gestation, dams
were randomized in two groups (n = 7 each): constant light (LL) and normal
photoperiod (12 h light/12 h dark; LD). At 18 days of gestation, RNA was isolated
from the fetal liver and subjected to DNA microarray (Affymetrix platform for
28,000 genes). Selected differential mRNAs were validated by quantitative PCR
(qPCR), while integrated transcriptional changes were analyzed with Ingenuity
Pathway Analysis and other bioinformatics tools. Comparison of LL relative to LD
fetal liver led to the following findings. Significant differential expression
was found for 3,431 transcripts (1,960 upregulated and 1,471 downregulated), with
393 of them displaying >= 1.5-fold change. We validated 27 selected transcripts
by qPCR, which displayed fold-change values highly correlated with microarray
(r(2) = 0.91). Different markers of nonalcoholic fatty liver disease were either
upregulated (e.g., Ndn and Pnpla3) or downregulated (e.g., Gnmt, Bhmt1/2,
Sult1a1, Mpo, and Mat1a). Diverse pathways were altered, including hematopoiesis,
coagulation cascade, complement system, and carbohydrate and lipid metabolism.
The microRNAs 7a-1, 431, 146a, and 153 were upregulated, while the abundant
hepatic miRNA 122 was downregulated. Constant gestational light induced extensive
modification of the fetal liver transcriptome. A number of differentially
expressed transcripts belong to fundamental functional pathways, potentially
contributing to long-term liver disease.
PMID- 26419526
TI - Regional inequalities in self-rated health and disability in younger and older
generations in Turkey: the contribution of wealth and education.
AB - BACKGROUND: In Turkey, large regional inequalities were found in maternal and
child health. Yet, evidence on regional inequalities in adult health in Turkey
remains fragmentary. This study aims to assess regional and rural/urban
inequalities in the prevalence of poor self-rated health and in disability among
adult populations in Turkey, and to measure the contribution of education and
wealth of individual residents. The central hypothesis was that geographical
inequalities in adult health exist even when the effect of education and wealth
were taken into account. METHODS: We analyzed data of the 2002 World Health
Survey for Turkey on 10791 adults aged 20 years and over. We measured
respondents' rating of their own general health and the prevalence of five types
of physical disability. Logistic regression was used to estimate how much these
two health outcomes varied according to urban/rural place of residence, region,
education level and household wealth. We stratified the analyses by gender and
age (<50 and >=50 years). RESULTS: Both health outcomes were strongly associated
with educational level (especially for older age group) and with household wealth
(especially for younger age group). Both health outcomes also varied according to
region and rural/urban place of residence. Higher prevalence rates were observed
in the East region (compared to West) with odd ratios varying between 1.40-2.76.
After controlling for education and wealth, urban/rural differences in health
disappeared, while regional differences were observed only among older women. The
prevalence of poor self-rated health was higher for older women in the Middle (OR
= 1.69), Black Sea (OR = 1.53) and East (OR = 2.06) regions. CONCLUSION: In
Turkey, substantial geographical inequalities in self-reported adult health do
exist, but can mostly be explained by differences in socioeconomic
characteristics of residents. The regional disadvantage of older women in the
East, Middle and Black Sea may have resulted from life-long exposure to gender
discrimination under a patriarchal ideology. Yet, not geographic inequalities,
but the more fundamental socioeconomic inequalities, are of key public health
concern, also in Turkey.
PMID- 26419528
TI - National Survey of Neurologists for Transient Ischemic Attack Risk Stratification
Consensus and Appropriate Treatment for a Given Level of Risks.
AB - BACKGROUND: Patients with a new transient ischemic attack (TIA) have a 5%
subsequent stroke risk within 7 days. The Canadian TIA Score accurately
determines the risk of subsequent stroke risk; however, it is unclear if
physicians will use this new scale or how it will be used. Our objectives were to
assess: (1) anticipated use; (2) component face validity; (3) risk strata for
stroke within 7 days; and (4) actions required, for a given risk for subsequent
stroke based on the proposed Canadian TIA Score. METHODS: After a rigorous
development process (sample selection, key informant interviews, development of
questionnaire following Dillman Tailored Design technique, cognitive interviews,
and pilot-testing), a survey questionnaire was administered to a random sample of
300 neurologists selected from all neurologists listed in a national medical
directory. The surveys were distributed using a modified Dillman technique.
RESULTS: From a total of 265 eligible surveys, we received 140 (52.8%) completed
surveys; 7 of 13 components comprising the Canadian TIA Score were rated as "very
important" or "important" by survey respondents. Risk categories for subsequent
stroke were defined as: minimal risk: less than 1%; low risk: 2%-4.9%; high risk:
5%-10%; critical risk: more than 10% risk of subsequent stroke within 7 days.
Most (87.1%) of the neurologists would use a validated Canadian TIA Score.
CONCLUSIONS: Neurologists appear ready to use a validated Canadian TIA Score in
their clinical practice. Risk strata are definable, which may allow physicians to
determine immediate actions, based on subsequent stroke risk.
PMID- 26419527
TI - Protocol Deviations before and after Treatment with Intravenous Tissue
Plasminogen Activator in Community Hospitals.
AB - BACKGROUND: Protocol deviations before and after tissue plasminogen activator
(tPA) treatment for ischemic stroke are common. It is unclear if patient or
hospital factors predict protocol deviations. We examined predictors of protocol
deviations and the effects of protocol violations on symptomatic intracerebral
hemorrhage (sICH). METHODS: We used data from the Increasing Stroke Treatment
through Interventional Behavior Change Tactics trial, a cluster-randomized,
controlled trial evaluating the efficacy of a barrier assessment and educational
intervention to increase appropriate tPA use in 24 Michigan community hospitals,
to review tPA treatments between 2007 and 2010. Protocol violations were defined
as deviations from the standard tPA protocol, both before and after treatment.
Multilevel logistic regression models were fitted to determine if patient and
hospital variables were associated with pretreatment or post-treatment protocol
deviations. RESULTS: During the study, 557 patients (mean age 70, 52% male,
median National Institutes of Health Stroke Scale score 12) were treated with
tPA. Protocol deviations occurred in 233 (42%) patients: 16% had pretreatment
deviations, 35% had post-treatment deviations, and 9% had both. The most common
protocol deviations included elevated post-treatment blood pressure,
antithrombotic agent use within 24 hours of treatment, and elevated pretreatment
blood pressure. Protocol deviations were not associated with sICH, stroke
severity, or hospital factors. Older age was associated with pretreatment
protocol deviations (adjusted odds ratio [OR], .52; 95% confidence interval [CI],
.30-.92). Pretreatment deviations were associated with post-treatment deviations
(adjusted OR, 3.20; 95% CI, 1.91-5.35). CONCLUSIONS: Protocol deviations were not
associated with sICH. Aside from age, patient and hospital factors were not
associated with protocol deviations.
PMID- 26419529
TI - Causes of Excessive Daytime Sleepiness in Patients with Acute Stroke--A
Polysomnographic Study.
AB - BACKGROUND: Sleep disorders are common in stroke patients. Sleep-disordered
breathing (SDB), which is present in up to 72% of stroke patients, is the most
frequent cause of excessive daytime sleepiness (EDS) in common population. The
aim of this study was to assess the frequency of EDS in stroke patients and to
analyze the impact of SDB, stroke severity, and location of stroke on EDS in the
acute phase of stroke. METHODS: We enrolled 102 patients with the clinical
diagnosis of acute stroke. Baseline clinical characteristics were recorded on
admission. An Epworth sleepiness scale score higher than 9 was considered as EDS.
To detect SDB, we performed standard overnight polysomnography within 4 +/- 2
days after the stroke onset. RESULTS: EDS was present in 21 patients (20.6%). In
a population with EDS, we found a significantly higher number of obstructive
apneic pauses, central apneic pauses, as well as significantly higher values of
respiratory disturbance index (RDI), RDI during nonrapid eye movement sleep,
desaturation index, and significant decrease of REM sleep duration. RDI (odds
ratio [OR], 1.031; 95% confidence interval [CI], 1.007-1.056; P = .01) and
duration of REM sleep (OR, .922; 95% CI, .853-.997; P = .042) were the only
independent variables significantly associated with EDS in a binary multivariate
regression model. CONCLUSION: SDB is a common, significant, and treatable cause
of EDS in acute stroke patients. We suppose that examination in sleep
laboratories is reasonable in all stroke patients with EDS, although the impact
of SDB therapy on EDS and overall outcome in acute stroke remains unknown.
PMID- 26419530
TI - The effect of oleic acid on the synthesis of Fe(3-x)O4 nanoparticles over a wide
size range.
AB - This work reports on the effect of the oleic acid concentration on the magnetic
and structural properties of Fe3-xO4 nanoparticles synthesized by thermal
decomposition of Fe(acac)3 in benzyl-ether. This method allows the synthesis of
highly monodisperse particles ranging from 7 to 100 nm in size by only varying
the concentration of oleic acid in the reaction mixture. The structural and
magnetic characterization reveal homogeneous particles in composition, with
narrow particle size distribution, which are single-phase magnetite with almost
bulk-like values of the saturation magnetization of about 90-99 emu g(-1) at low
temperatures and show the characteristic anomaly in the zero field-cooling
magnetization curves associated with the Verwey transition for nanoparticles
bigger than about 7 nm. In addition, the analyses of aliquots of the reaction
mixtures by Fourier transform infrared spectroscopy at various stages shed light
on the nucleation and growth processes of the particles.
PMID- 26419531
TI - Cultivation of stable, reproducible microbial communities from different fecal
donors using minibioreactor arrays (MBRAs).
AB - BACKGROUND: Continuous-flow culture models are one tool for studying complex
interactions between members of human fecal microbiotas because they allow
studies to be completed during an extended period of time under conditions where
pH, nutrient availability, and washout of waste products and dead cells can be
controlled. Because many of the existing well-validated continuous-flow models
are large and complex, we were interested in developing a simpler continuous-flow
system that would allow microbial community dynamics to be examined in higher
throughput while still maintaining complex microbial communities. To this end, we
developed minibioreactor arrays (MBRAs), small volume bioreactors (15 ml) that
allow simultaneous cultivation of up to 48 microbial communities in a single
anaerobic chamber. RESULTS: We used MBRA to characterize the microbial community
dynamics of replicate reactors inoculated from three different human fecal donors
and reactors seeded with feces pooled from these three donors. We found that MBRA
could be used to efficiently cultivate complex microbial communities that were a
subset of the initial fecal inoculum (15-25 % of fecal OTUs initially observed).
After an initial acclimation period of approximately 1 week, communities in each
reactor stabilized and exhibited day-to-day variation similar to that observed in
stable mouse fecal communities. Replicate reactors were predominately populated
by shared core microbial communities; variation between replicate reactors was
primarily driven by shifts in abundance of shared operational taxonomic units
(OTUs). Consistent with differences between fecal donors, MBRA communities
present in reactors seeded with different fecal samples had distinct composition
and structure. CONCLUSIONS: From these analyses, we conclude that MBRAs can be
used to cultivate communities that recapitulate key features of human fecal
communities and are a useful tool to facilitate higher-throughput studies of the
dynamics of these communities.
PMID- 26419532
TI - Evaluation of the use of clinical decision support and online resources for
pharmacogenomics education.
AB - AIM: To assess impact and value of using clinical decision support (CDS) to drive
providers toward online pharmacogenomics education. MATERIALS & METHODS: CDS was
used to target prescribers of codeine/tramadol, send an educational email,
display alert/inbox and provide links to an online resource. Providers were
surveyed to assess impact. RESULTS: Of the methods used to target providers,
educational email was more effective (7.2%). Survey response rate was 29.2% (n =
528/1817). Of respondents, 57.4% reported opening the email and 27.1% accessed
the online resource. Of those accessing the resource, 89% found it useful and
learned something new about pharmacogenomics. CONCLUSION: The impact of using CDS
to target pharmacogenomics education was limited. However, providers accessing
the online resource found it useful and educational.
PMID- 26419534
TI - Intensive care in a private hospital: An option for emergency medicine trainees?
PMID- 26419533
TI - Motives for dish choices during home meal preparation: results from a large
sample of the NutriNet-Sante study.
AB - BACKGROUND: Although culinary practices have strongly evolved over time, few data
are available on contemporary dish choices during meal preparation. We therefore
sought to determine individual motives when choosing dishes to be prepared during
weekdays and on weekends. METHODS: The importance of 27 criteria related to dish
choices was assessed in 53,025 participants in the NutriNet-Sante study.
Dimensions of dish choice motives were investigated using exploratory factor
analysis. Mean ratings of motives during weekdays and on weekends were compared
using Student's t-test. Association between socio-demographic and cooking
practice characteristics, and dish choice motives were evaluated using logistic
regression models. RESULTS: Five dimensions of dish choice motives emerged:
healthy diet (explained variance: 48.3%), constraints (19.0%), pleasure (12.1%),
specific diets (11.0%) and organization (9.6%). The healthy diet factor was the
most important on weekdays (mean rating 3.93) and weekends (3.90). Pleasure
(3.61) had a higher score than constraints (3.54) on weekends (p < 0.0001) while
the opposite was observed on weekdays (3.42 vs 3.77, respectively) (p < 0.0001).
Organization was more important on weekdays (2.89) than on weekends (2.75) (p <
0.0001). Dish choice motives appeared to be significantly associated with socio
demographic and cooking practice characteristics. CONCLUSION: This study
highlighted factors involved in dish choices in meal preparation on weekdays and
weekends, as well as individual characteristics which determine motives for dish
choices. From a public health perspective, these findings might help to develop
appropriate strategies for promoting home meal preparation.
PMID- 26419535
TI - Root causes for delayed hospital discharge in patients with ST-segment Myocardial
Infarction (STEMI): a qualitative analysis.
AB - BACKGROUND: The majority of patients who suffer a ST-segment myocardial
infarction (STEMI) are hospitalized for longer than 48 h. With the advent of
reperfusion therapy, the benefits of such extended hospitalization has been
questioned. The goal of this qualitative study was to identify the root causes
for prolonged hospitalization in STEMI patients in order to refine future
interventions to optimize the length of hospitalization. METHODS: Practitioners
involved in the discharge process for STEMI patients at a single tertiary care
STEMI center underwent semi-structured interviews focused on three fictional
patient cases. Data were transcribed and analyzed for key themes by thematic
analysis. RESULTS: Interviews were conducted with 17 practitioners (5 Attending
Physicians, 4 Internal Medicine Residents, 4 Cardiology Residents, 4 Nursing
Staff). The key themes were patient factors, provider factors, and transitions to
outpatient care. Patient factors included concerns that early discharge would
limit dose titration of medications, the educational experience of the patient,
and prevent monitoring for complications. Provider factors included past clinical
experience with STEMI complications, in turn impacting discharging behaviour.
Transitions of care factors were difficulty in establishing reliable follow-up
plans and home care services. CONCLUSIONS: Several themes were identified that
influence the timing of discharge post STEMI. The majority of these issues are
not incorporated into currently available post STEMI risk stratification tools.
Future quality improvement interventions to reduce STEMI length of stay should
focus on in-patient and out-patient strategies to address these unique clinical
situations.
PMID- 26419536
TI - Causes of end stage renal failure among haemodialysis patients in Khartoum
State/Sudan.
AB - BACKGROUND: End stage renal failure (ESRF) has become a major health problem in
Sub Saharan Africa (SSA). There were limited data about causes of ESRF in the
Sudan. METHODS: This is a cross sectional hospital based descriptive study. The
subjects of the study are ESRF adults' patients on regular haemodialysis
treatment in 15 haemdoialysis centres in Khartoum State-Sudan. Clinical and
epidemiological data were obtained from 1583 patients. The medical files of each
patient were reviewed to identify the cause of ESRF. Concerning the causes of
ESRF, diabetes was diagnosed based on the past medical history and result of the
glucose tolerance test, hypertension was diagnosed based on past history of
hypertension based on blood pressure of more than 140/90 mmHg, glomerulonephritis
was diagnosed based on results of previous kidney biopsies and on clinical
grounds, polycystic kidney disease and obstructive uropathy were diagnosed based
on abdominal ultrasound and other imaging modalities, sickle cell anaemia was
diagnosed based on the result of haemoglobin electrophoresis, systemic lupus
erythematosus was diagnosed based on the clinical criteria in addition to lab
results of auto antibodies, and analgesic nephropathy was diagnosed based on past
medical history of chronic analgesic drugs usage with no other identifiable risk
factors. We included all ESRF patients on regular haemodialysis treatment. We
excluded ESRF patients less than 18 years old. RESULTS: The results showed that
the mean age of ESRF Patients was 49 +/- 15.8 (years) and 63.4% were male and
76.3% were unemployed. The mean duration of haemodialysis is 4.38 +/- 4.24
(years). The most common cause of ESRF in our patients was hypertension (34.6%)
followed by chronic glomerulonephritis (17.6%), diabetes mellitus (12.8%),
obstructive uropathy (9.6 %), autosomal dominant poly cystic kidney disease
(ADPKD) (4.7%), chronic pyelonephritis (4.6%), analgesic nephropathy (3.5%).
However in (10.7%) no cause was found. In patient aged less than 40 years old the
leading cause of ESRF was glomerulonephritis (29.3%) followed by hypertension
(25%). In patient aged between 40 to 60 years old the leading cause of ESRF was
hypertension (38.5%) followed by diabetes mellitus (14%). In patient aged older
than 60 years the leading cause of ESRF was hypertension (38.4%) followed by
diabetes mellitus (23.3%). CONCLUSIONS: ESRF in Sudan affects the economically
productive age group; unemployment rate among ESRF patients is high. The study
showed that hypertension is a leading cause of ESRF in Sudan followed by chronic
glomerulonephritis. Hypertension and diabetes mellitus are the leading causes of
ESRF among patients over 40 years old.
PMID- 26419538
TI - In vitro/in vivo correlations in transdermal product development.
AB - As per the US FDA's guidance for industry entitled 'Extended Release Oral Dosage
Forms: Development, Evaluation, and Application of In Vitro/In Vivo
Correlations', in vitro-in vivo correlations (IVIVC) can be used to establish a
dissolution test as a surrogate for human bioequivalence studies and certain
scale-up and postapproval changes. However, at the present time, establishment of
a transdermal IVIVC is not used to support biowaiver claims in late phases of
clinical development or postapproval changes (major formulation changes, i.e.,
>10% changes in inactive ingredients) to the best of the authors' knowledge. The
value of developing an IVIVC for percutaneous drugs lies mainly in facilitating
permeation testing of transdermal drug candidates and formulation performance
optimization at much lower cost as compared with carrying out multiple in vivo
studies. The present article will introduce the concept of transdermal IVIVC,
outlining certain limitations to its applicability, in vitro and in vivo methods,
regulatory product development requirements and the most common approaches to
establish an IVIVC for a transdermal drug. Additionally, this article will also
summarize some challenges and recent advancements in this field, along with
selected academic examples of transdermal IVIVCs.
PMID- 26419539
TI - Palladium(II) complexes featuring a mixed phosphine-pyridine-iminophosphorane
pincer ligand: synthesis and reactivity.
AB - An original mixed ligand (labelled L) of formula PPh2-CH2-Pyr-CH2-N[double bond,
length as m-dash]PPh3, combining a pyridine core with phosphine and
iminophosphorane, was synthesised. Its coordination with palladium(II) centers
was studied. With [Pd(COD)Cl2], a cationic complex [LPdCl](Cl) 1, where L is
coordinated in the pincer mode, was obtained. Chloride abstraction with silver
salt in the presence of pyridine generated the dicationic complex [LPd(py)](BF4)2
(2). When reacting with a base such as potassium hexamethyldisilazane (KHMDS), 1
gave the neutral complex 3 [L*PdCl], wherein the benzylic position alpha to
phosphine was selectively deprotonated, which induced dearomatisation of the
pyridine ring. A similar complex [L*Pd(CH3)] (4) was obtained upon a reaction of
[Pd(CH3)2(TMEDA)] and Lvia the departure of methane. Neutral complexes with the
deprotonated ligand such as 3 yielded in the presence of deuterated methanol the
corresponding deuterated complex, showing that the protonation is reversible with
this ligand. Finally, upon attempting to dealkylate complex 4 using B(C6F5)3, an
unexpected zwitterionic borated complex 5, resulting from the formation of a C-B
bond in the benzylic position with restoration of the aromatic character of the
pyridine, was isolated. Interestingly, when the metal was introduced after the
ligand interacted with the borane reagent, another palladium complex formed,
namely, [LPdMe][MeB(C6F5)3], originating from methyl abstraction.
PMID- 26419537
TI - Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF
16/FOXO target gene expression.
AB - BACKGROUND: Many neurodegenerative diseases are associated with protein
misfolding/aggregation. Treatments mitigating the effects of such common
pathological processes, rather than disease-specific symptoms, therefore have
general therapeutic potential. RESULTS: Here we report that the anti-epileptic
drug ethosuximide rescues the short lifespan and chemosensory defects exhibited
by C. elegans null mutants of dnj-14, the worm orthologue of the DNAJC5 gene
mutated in autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. It also
ameliorates the locomotion impairment and short lifespan of worms expressing a
human Tau mutant that causes frontotemporal dementia. Transcriptomic analysis
revealed a highly significant up-regulation of DAF-16/FOXO target genes in
response to ethosuximide; and indeed RNAi knockdown of daf-16 abolished the
therapeutic effect of ethosuximide in the worm dnj-14 model. Importantly,
ethosuximide also increased the expression of classical FOXO target genes and
reduced protein aggregation in mammalian neuronal cells. CONCLUSIONS: We have
revealed a conserved neuroprotective mechanism of action of ethosuximide from
worms to mammalian neurons. Future experiments in mouse neurodegeneration models
will be important to confirm the repurposing potential of this well-established
anti-epileptic drug for treatment of human neurodegenerative diseases.
PMID- 26419540
TI - Competencies in Occupational and Environmental Health Nursing.
PMID- 26419541
TI - Ebola Update.
AB - The Ebola virus disease first appeared in 1976 in the Sudan and the Democratic
Republic of Congo. The most recent outbreak occurred in West Africa in March 2014
and quickly spread in surrounding countries. Ebola spreads through direct contact
with the body fluids of an infected individual. The incubation period for Ebola
is 2 to 21 days. Individuals are infectious when symptomatic. Identifying
individuals at high risk for Ebola in the United States includes early
recognition of symptoms and a history of travel to an Ebola-affected area.
Multiple diagnostic tests exist and should include a complete blood count and a
comprehensive metabolic profile. Standard, contact, and droplet precautions are
advised when taking care of patients with Ebola. Appropriate personal protective
equipment as recommended by the Centers for Disease Control and Prevention should
be worn. No vaccine or antiviral drug has been approved, but vaccine trials are
under way. Occupational health nurses play a key role in educating employees
about this disease.
PMID- 26419542
TI - Health Effects of Vanpooling to Work.
AB - Shared commutes to work, such as vanpooling, benefit the environment and provide
economic gain for riders in terms of fuel costs, parking fees, and personal
vehicle wear and tear. Although ride sharing is commonly believed to promote
health through stress reduction, published evidence on this topic is limited, and
findings vary. This study explored the perceived health and well-being of
vanpoolers using a qualitative, descriptive design. Five focus groups of
vanpoolers and two individual interviews with drivers were conducted (N=40
participants). Stress, change in sleep patterns, and interpersonal relationships
emerged as major themes. Employee insights about the impact of vanpooling on work
productivity and how employer commitment to the vanpool program influences the
vanpool experience also were important findings.
PMID- 26419543
TI - Formaldehyde Level in Anatomy Laboratory Teaching Room and Risk for Cancer.
PMID- 26419544
TI - AAOHN Competencies.
AB - The AAOHN Competency document is one of the core documents that define
occupational health nursing practice. This article provides a description of the
process used to update the competencies, as well as a description of the new
competencies.
PMID- 26419545
TI - Nanobiotechnological Approaches Against Multidrug Resistant Bacterial Pathogens:
An Update.
AB - Multiple drug resistant bacteria remain the greatest challenge in public health
care. Globally, infections produced by such resistant strains are on the rise.
Recent advent of genetic tolerance to antibiotics in many pathogens such as
multiple drug resistant Staphylococcus aureus is a matter of concern, prompting
researchers and pharmaceutical companies to search for new molecules and
unconventional antibacterial agents. Recent advances in nanotechnology offer new
opportunities to develop formulations based on metallic nanoparticles with
different shapes and sizes and variable antimicrobial properties. This article is
an extensive literature review that covers the latest approaches in the
development of new and unconventional antibacterial agents using
nanobiotechnological approaches which will better equip scientists and clinicians
to face the challenges in view of dwindling stocks of effective and potent
antimicrobial agents and formulations.
PMID- 26419546
TI - Fumonisins: oxidative stress-mediated toxicity and metabolism in vivo and in
vitro.
AB - Fumonisins (FBs) are widespread Fusarium toxins commonly found as corn
contaminants. FBs could cause a variety of diseases in animals and humans, such
as hepatotoxic, nephrotoxic, hepatocarcinogenic and cytotoxic effects in mammals.
To date, almost no review has addressed the toxicity of FBs in relation to
oxidative stress and their metabolism. The focus of this article is primarily
intended to summarize the progress in research associated with oxidative stress
as a plausible mechanism for FB-induced toxicity as well as the metabolism. The
present review showed that studies have been carried out over the last three
decades to elucidate the production of reactive oxygen species (ROS) and
oxidative stress as a result of FBs treatment and have correlated them with
various types of FBs toxicity, indicating that oxidative stress plays critical
roles in the toxicity of FBs. The major metabolic pathways of FBs are hydrolysis,
acylation and transamination. Ceramide synthase, carboxylesterase FumD and
aminotransferase FumI could degrade FB1 and FB2. The cecal microbiota of pigs and
alkaline processing such as nixtamalization can also transform FB1 into
metabolites. Most of the metabolites of FB1 were less toxic than FB1, except its
partial (pHFB1) metabolites. Further understanding of the role of oxidative
stress in FB-induced toxicity will throw new light on the use of antioxidants,
scavengers of ROS, as well as on the blind spots of metabolism and the
metabolizing enzymes of FBs. The present review might contribute to reveal the
toxicity of FBs and help to protect against their oxidative damage.
PMID- 26419548
TI - Deciding what really matters.
AB - England's chief nursing officer (CNO) Jane Cummings has called for senior nurses
and other healthcare professionals to engage with the development of a strategy
to follow Compassion in Practice ( page 7 ).
PMID- 26419547
TI - Trans-scleral diode laser cyclophotocoagulation for refractory glaucoma after
high-risk penetrating keratoplasty.
AB - To analyze the intraocular pressure reduction, number of anti-glaucoma
medications needed, and post-operative complications of trans-scleral diode laser
cyclophotocoagulation (DCPC) in patients with high-risk penetrating keratoplasty
(PKP) and secondary refractory glaucoma. Prospective interventional,
longitudinal, non-comparative series of cases, including 16 eyes of 15 patient's
post-PKP on maximal anti-glaucoma medical therapy with intraocular pressures
above 22 mmHg. All patients received 18 shots, 360 degrees peri-limbal (avoiding
the long posterior ciliary nerves and arteries at 3 and 9 o'clock positions) of
trans-scleral DCPC (2000 mW, time: 2.0 s/shot). There was a 55.5 % reduction
(total of 14.0 mmHg) of the mean pre-operative IOP (31.5 mmHg) after the first
diode laser application (p = 0.0020). Re-treatment was required in 31.2 % of eyes
over a mean period of 10.7 months. In these five eyes, the mean pre-operative IOP
was 40.4 mmHg, which decreased to 15.0 mmHg post-therapy, and a mean IOP
reduction of 25.4 mmHg (p = 0.0218). There was a 51.0 % reduction in the mean
number of medications used after the first, and a 57.1 % reduction after a second
laser application. The incidence of failure (IOP >= 22 mmHg or need of additional
medical therapy) from initial intervention to loss of follow-up was 1.3 % per
person-month. DCPC effectively reduces the intraocular pressure and the number of
anti-glaucoma medications with few complications in patients after high-risk PKP
and secondary glaucoma. Only, one-third of the eyes needed a second intervention
to control the intraocular pressure. Post-DCPC complications were limited to
phthisis bulbi and endothelial dysfunction, one eye each. Please check and
confirm the author names and initials are correct. Also, kindly confirm the
details in the metadata are correct.
PMID- 26419549
TI - Providers to face monthly monitoring over agency spends.
AB - MONITOR AND the NHS Trust Development Authority have published rules to help NHS
providers cut the cost of employing agency staff.
PMID- 26419550
TI - Films show loud music interferes with smooth operation of theatres.
AB - LOUD MUSIC played in operating theatres hinders the ability of nurses to hear
instructions, a study has shown.
PMID- 26419551
TI - Standards for pain management unveiled by college forum.
AB - THE RCN has launched a knowledge and skills framework to help nursing teams
assess and manage pain.
PMID- 26419554
TI - Chief nurse welcomes topics for next nursing strategy.
AB - ENGLAND'S CHIEF nurse Jane Cummings is urging nurses to advise her on the focus
of the next nursing strategy.
PMID- 26419553
TI - L5 million initiative to cut staff absence announced.
AB - A DRIVE to improve NHS staff health will fail unless one of the main causes of
stress, namely lack of staff, is tackled, say unions.
PMID- 26419555
TI - Online health records offer patients chance to correct their notes.
AB - PATIENTS WILL be able by 2018 to access their entire health records
electronically and add their own notes, the health secretary has announced.
PMID- 26419556
TI - Political influence.
AB - SENIOR NURSES in Northern Ireland are to be trained in political influencing to
help them understand better the political landscape of the country, and how they
can help to shape policy on behalf of nurses and nursing.
PMID- 26419557
TI - Chief nursing officer for Ireland aims to 'bring nurses together'.
AB - WHEN IRELAND'S chief nursing officer (CNO) Siobhan O'Halloran was appointed to
her post two years ago this month, she was determined to join nurses together,
not just between the different nursing branches but geographically too.
PMID- 26419558
TI - Benefits of a narrative culture.
AB - LOOKING BACK over the past 20 years, the healthcare challenges we faced then are
similar to those we face now. They may be heightened, but they still concern
quality and safety, healthcare equity, cost constraints, and regulatory
requirements.
PMID- 26419565
TI - Vantage point - A 'wicked' problem.
AB - SENIOR NURSES everywhere are facing a 'wicked' problem, wicked in the sense that
it seems to defy resolution. The problem is this: the national shortage of
nurses, particularly of those at band 5, is forcing us to use agency nurses so
that we have enough staff to provide patient care safely.
PMID- 26419566
TI - Community question.
AB - THE BED manager scanned the whiteboard in the busy office of an acute psychiatric
ward. 'What about this man, WL?' she asked. 'He's been in for nearly two weeks.
Can he go on weekend leave?' The nurse in charge was sceptical, but an urgent
admission was imminent, and there was no room. So WL was informed that he was
ready for a trial period at home, and his bed was swiftly changed for the new
arrival. Such is life in the inner-city psychiatric ward, where demand
relentlessly exceeds supply.
PMID- 26419568
TI - Beat (Beat Eating Disorders).
AB - This charity website provides a comprehensive range of information on eating
disorders. There is an overview section about different types of eating
disorders, which is in clear and easily understood terms, giving readers the
option to seek more detailed information.
PMID- 26419569
TI - Deprivation of liberty.
PMID- 26419570
TI - Emotional wellbeing.
PMID- 26419571
TI - Social network.
AB - The Better Care Exchange is a social network for health and social care
professionals that enables information and knowledge sharing on good practice and
better integrated care, and the implementation of Better Care Fund plans.
PMID- 26419572
TI - Consultations.
PMID- 26419573
TI - Inspiring undergraduates towards a career in community nursing.
AB - This article is based on the findings of a literature review commissioned by the
Queen's Nursing Institute Scotland as part of its commitment to promote an
evidence-based educational policy. An analysis of the literature suggests that
there is potential to expand the provision of community placements beyond
traditional clinical areas and these placements should be identified and overseen
in collaboration with managers, mentors and higher education institutions to
ensure a consistent approach and a positive learning experience. This may inspire
undergraduate nurses to pursue a career in community nursing. Currently, there is
little evidence to support models. High-quality evaluation research is required
to ensure that new models are developed using a sound evidence base.
PMID- 26419574
TI - Nurse practitioners changing health behaviours: one patient at a time.
AB - In 2005, legislation was enacted allowing nurse practitioners (NPs) to practise
in British Columbia, Canada. Although substantial human and financial resources
had been dedicated to the implementation of the role, no evaluation has been
conducted to date. As part of a larger multiphase, mixed-methods study design,
which evaluated the integration of NPs into the British Columbia healthcare
system, this article describes findings related to changes that result for
patients and the implications for the healthcare system when NPs become part of
the care process. Using survey and interview data, themes that emerged were
patient satisfaction, access to care, and behavioural changes. Findings suggest
that patients are satisfied with the care they receive from NPs and that NPs make
positive changes to health behaviour.
PMID- 26419575
TI - Revalidation: implications for senior nurses.
AB - Revalidation replaces the current triennial self-declaration system of
maintaining nurse registration. It involves a third-party affirmation process
designed to improve public and patient confidence that nurses remain up to date
by undertaking relevant professional development activities. While revalidation
is ultimately the responsibility of individual nurses, senior nurses have an
important facilitating role in ensuring that registrants can remain on the
register and so continue to practise. This article outlines, from a practical
perspective, the senior nurse's role and responsibilities in supporting
registrants through each stage of the revalidation process.
PMID- 26419576
TI - 'I wanted to be boss'.
AB - The ability to decide what has to be done now and what can wait has served Royal
Blackburn Hospital matron for medicine and the medical admissions unit Lesley Gaw
well in the three decades that she's been scaling the leadership ladder. But it
could all have been so different, as Jennifer Trueland discovered when she met
the innovative nurse manager.
PMID- 26419577
TI - Benefits of a Dual Chemical and Physical Activation: Direct aza-Michael Addition
of Anilines Promoted by Solvent Effect under High Pressure.
AB - The unique combination of hexafluoroisopropanol (HFIP) employed as solvent and
hyperbaric conditions (10-15 kbar) allows unprecedented 1,4-addition of poor
nucleophiles, such as aromatic amines, onto sluggish (cumbersome) Michael
acceptors without any promoter or workup.
PMID- 26419578
TI - Very Late Thrombosis of a Bioresorbable Scaffold.
PMID- 26419579
TI - The "De Winter Pattern" Can Progress to ST-segment Elevation Acute Coronary
Syndrome. Response.
PMID- 26419580
TI - Guidelines on the Management of Implantable Cardioverter-defibrillators at the
End of Life. Response.
PMID- 26419581
TI - Circadian aspects of myocardial infarction among young STEMI patients.
PMID- 26419582
TI - Current developments in cell- and biomaterial-based approaches for stroke repair.
AB - INTRODUCTION: Stroke is one of the most devastating diseases and a leading cause
of mortality worldwide. So far, clinical management of stroke involves surgical
clot retrieval or thrombolytic treatment inducing reperfusion of the occluded
vessels in the cerebral infarcted area, which is dependent on early intervention
following insult. New treatment strategies involve the promotion of angiogenesis
and neuroplasticity, stimulation of endogenous neurogenesis, remyelinization, and
immunomodulation by means of cell transplantation and sustained drug delivery.
AREAS COVERED: This review describes different types of stem cells (endogenous
and exogenous neural progenitors, pluripotent stem cell derivatives, mesenchymal
stem cells [MSCs], olfactory ensheathing cells) and biomaterials, their routes of
administration, means of noninvasive imaging, and the prerequisites and hurdles
for the successful translation of the cell therapies to the clinic. EXPERT
OPINION: Neural precursors (NPs) derived from pluripotent stem cells, unlike
MSCs, can not only remodel the CNS by promoting neuroplasticity, angiogenesis,
and immunomodulation, but also replace damaged cells. To transfer NPs into the
clinic, step by step guidelines for researchers are identified and discussed.
PMID- 26419583
TI - Daily intake of fermented milk with Lactobacillus casei strain Shirota reduces
the incidence and duration of upper respiratory tract infections in healthy
middle-aged office workers.
AB - PURPOSE: Although several studies have demonstrated the efficacy of probiotics
for preventing upper respiratory tract infections (URTIs) in at-risk populations,
including children and the elderly, few studies have investigated the efficacy of
probiotics in healthy adults living normal, everyday lives. Thus, we tried to
evaluate the effects of Lactobacillus casei strain Shirota-fermented milk (LcS
FM) on the incidence of URTIs in healthy middle-aged office workers. METHODS: In
a randomized controlled trial, 96 eligible male workers aged 30-49 years consumed
LcS-FM containing 1.0 * 1011 viable LcS cells or control milk (CM) once daily for
12 weeks during the winter season. URTI episodes were evaluated by a physician
via a questionnaire of URTI symptoms. RESULTS: The incidence of URTIs during the
intervention period was significantly lower in the LcS-FM group than in the CM
group (22.4 vs. 53.2 %, P = 0.002). The time-to-event analysis showed that the
LcS-FM group had a significantly higher URTI-free rate than the CM group over the
test period (log-rank test: chi 2 11.25, P = 0.0008). The cumulative number of
URTI episodes and cumulative days with URTI symptoms per person was lower in the
LcS-FM group, and the duration per episode was shorter. Inhibition of both
reductions in NK cell activity in peripheral blood mononuclear cells and
increases in salivary cortisol levels was observed in the LcS-FM group.
CONCLUSION: The results suggest that the daily intake of fermented milk with LcS
may reduce the risk of URTIs in healthy middle-aged office workers, probably
through modulation of the immune system.
PMID- 26419584
TI - Waist circumference, trunk and visceral fat cutoff values for detecting
hyperinsulinemia and insulin resistance in children: the Healthy Growth Study.
PMID- 26419585
TI - Food intake and inflammation in European children: the IDEFICS study.
AB - PURPOSE: This cross-sectional study assesses the relationship between consumption
frequencies of food items and high-sensitivity C-reactive protein (hs-CRP) in
European children. METHODS: Out of the baseline sample (N = 16.228) of the
IDEFICS study, 6.403 children (1.315 boys aged 2 to <6, 1.908 boys aged 6 to <10,
1.204 girls aged 2 to <6 and 1.976 girls aged 6 to <10 years) had hs-CRP measured
and the Children's Eating Habits Questionnaire filled, including a food frequency
questionnaire. Logistic regression adjusted for body mass index z-score,
education of the mother, breast-feeding and self-reported hours of physical
activity in a sport club per week was conducted. RESULTS: Mean frequency intake
of raw vegetable was lower in boys (p = 0.022 in young and p = 0.020 in old) and
older girls (p = 0.026) with high hs-CRP concentration, while in younger girls (p
= 0.008) the same occurred with the cooked vegetables. The probability of having
higher hs-CRP concentration was significantly associated with having low
consumption frequency of vegetables (p = 0.004 in older boys, raw vegetables; and
p = 0.0032 in younger girls, cooked vegetables). Also, honey/jam intake decreased
the probability of having higher concentration of hs-CRP, whereas soft drinks
with sugar, mayonnaise and cereals milled increased this probability.
CONCLUSIONS: Out of all food items associated with hs-CRP, frequency intake of
vegetables presented more associations across all the analysis. Findings suggest
that a high-frequency intake of vegetables is inversely related to an
inflammatory status in children. More studies are needed to assess the
association between diet and inflammation.
PMID- 26419587
TI - Erratum to: Decreasing Recurrence Rates for Ductal Carcinoma In Situ: Analysis of
2996 Women Treated with Breast-Conserving Surgery Over 30 Years.
PMID- 26419586
TI - Betaine is as effective as folate at re-synthesizing methionine for protein
synthesis during moderate methionine deficiency in piglets.
AB - PURPOSE: Both folate and betaine (synthesized from choline) are nutrients used to
methylate homocysteine to reform the amino acid methionine following donation of
its methyl group; however, it is unclear whether both remethylation pathways are
of equal importance during the neonatal period when remethylation rates are high.
Methionine is an indispensable amino acid that is in high demand in neonates not
only for protein synthesis, but is also particularly important for
transmethylation reactions, such as creatine and phosphatidylcholine synthesis.
The objective of this study was to determine whether supplementation with folate,
betaine, or a combination of both can equally re-synthesize methionine for
protein synthesis when dietary methionine is limiting. METHODS: Piglets were fed
a low methionine diet devoid of folate, choline, and betaine, and on day 6,
piglets were supplemented with either folate, betaine, or folate + betaine (n = 6
per treatment) until day 10. [1-13C]-phenylalanine oxidation was measured as an
indicator of methionine availability for protein synthesis both before and after
2 days of supplementation. RESULTS: Prior to supplementation, piglets had lower
concentrations of plasma folate, betaine, and choline compared to baseline with
no change in homocysteine. Post-supplementation, phenylalanine oxidation levels
were 20-46 % lower with any methyl donor supplementation (P = 0.006) with no
difference among different supplementation groups. Furthermore, both methyl
donors led to similarly lower concentrations of homocysteine following
supplementation (P < 0.05). CONCLUSIONS: These data demonstrate an equal capacity
for betaine and folate to remethylate methionine for protein synthesis, as
indicated by lower phenylalanine oxidation.
PMID- 26419588
TI - AMPKalpha is essential for acute exercise-induced gene responses but not for
exercise training-induced adaptations in mouse skeletal muscle.
AB - Exercise training increases skeletal muscle expression of metabolic proteins
improving the oxidative capacity. Adaptations in skeletal muscle by
pharmacologically induced activation of 5'-AMP-activated protein kinase (AMPK)
are dependent on the AMPKalpha2 subunit. We hypothesized that exercise training
induced increases in exercise capacity and expression of metabolic proteins, as
well as acute exercise-induced gene regulation, would be compromised in muscle
specific AMPKalpha1 and -alpha2 double-knockout (mdKO) mice. An acute bout of
exercise increased skeletal muscle mRNA content of cytochrome c oxidase subunit
I, glucose transporter 4, and VEGF in an AMPK-dependent manner, whereas cluster
of differentiation 36 and fatty acid transport protein 1 mRNA content increased
similarly in AMPKalpha wild-type (WT) and mdKO mice. During 4 wk of voluntary
running wheel exercise training, the AMPKalpha mdKO mice ran less than WT.
Maximal running speed was lower in AMPKalpha mdKO than in WT mice but increased
similarly in both genotypes with exercise training. Exercise training increased
quadriceps protein content of ubiquinol-cytochrome c reductase core protein 1
(UQCRC1), cytochrome c, hexokinase II, plasma membrane fatty acid-binding
protein, and citrate synthase activity more in AMPKalpha WT than in mdKO muscle.
However, analysis of a subgroup of mice matched for running distance revealed
that only UQCRC1 protein content increased more in WT than in mdKO mice with
exercise training. Thus, AMPKalpha1 and -alpha2 subunits are important for acute
exercise-induced mRNA responses of some genes and may be involved in regulating
basal metabolic protein expression but seem to be less important in exercise
training-induced adaptations in metabolic proteins.
PMID- 26419590
TI - Effects of acute exercise on lipid content and dietary lipid uptake in liver and
skeletal muscle of lean and diabetic rats.
AB - Insulin resistance is associated with ectopic lipid accumulation. Physical
activity improves insulin sensitivity, but the impact of exercise on lipid
handling in insulin-resistant tissues remains to be elucidated. The present study
characterizes the effects of acute exercise on lipid content and dietary lipid
partitioning in liver and skeletal muscle of lean and diabetic rats by use of
magnetic resonance spectroscopy (MRS). After baseline measurements, rats were
randomized to exercise or no-exercise groups. A subset of animals was subjected
to MRS directly after 1 h of treadmill running for measurement of total
intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) content (n=7
lean and diabetic rats). The other animals were administered 13C-labeled lipids
orally after treadmill visit (with or without exercise) followed by MRS
measurements after 4 and 24 h to determine the 13C enrichment of IHCL and IMCL
(n=8 per group). Total IHCL and IMCL content were fivefold higher in diabetic vs.
lean rats (P<0.001). Exercise did not significantly affect IHCL content but
reduced IMCL by 25+/-7 and 33+/-4% in lean and diabetic rats (P<0.05),
respectively. Uptake of dietary lipids in liver and muscle was 2.3-fold greater
in diabetic vs. lean rats (P<0.05). Prior exercise did not significantly modulate
dietary lipid uptake into muscle, but in liver of both lean and diabetic rats,
lipid uptake was 44% reduced after acute exercise (P<0.05). In conclusion, IMCL
but not IHCL represents a viable substrate source during exercise in both lean
and diabetic rats, and exercise differentially affects dietary lipid uptake in
muscle and liver.
PMID- 26419589
TI - Dominant negative FADD dissipates the proapoptotic signalosome of the unfolded
protein response in diabetic embryopathy.
AB - Endoplasmic reticulum (ER) stress and caspase 8-dependent apoptosis are two
interlinked causal events in maternal diabetes-induced neural tube defects
(NTDs). The inositol-requiring enzyme 1alpha (IRE1alpha) signalosome mediates the
proapoptotic effect of ER stress. Diabetes increases tumor necrosis factor
receptor type 1R-associated death domain (TRADD) expression. Here, we revealed
two new unfolded protein response (UPR) regulators, TRADD and Fas-associated
protein with death domain (FADD). TRADD interacted with both the IRE1alpha-TRAF2
ASK1 complex and FADD. In vivo overexpression of a FADD dominant negative (FADD
DN) mutant lacking the death effector domain disrupted diabetes-induced IRE1alpha
signalosome and suppressed ER stress and caspase 8-dependent apoptosis, leading
to NTD prevention. FADD-DN abrogated ER stress markers and blocked the JNK1/2
ASK1 pathway. Diabetes-induced mitochondrial translocation of proapoptotic Bcl-2
members mitochondrial dysfunction and caspase cleavage were also alleviated by
FADD-DN. In vitro TRADD overexpression triggered UPR and ER stress before
manifestation of caspase 3 and caspase 8 cleavage and apoptosis. FADD-DN
overexpression repressed high glucose- or TRADD overexpression-induced IRE1alpha
phosphorylation, its downstream proapoptotic kinase activation and endonuclease
activities, and apoptosis. FADD-DN also attenuated tunicamycin-induced UPR and ER
stress. These findings suggest that TRADD participates in the IRE1alpha
signalosome and induces UPR and ER stress and that the association between TRADD
and FADD is essential for diabetes- or high glucose-induced UPR and ER stress.
PMID- 26419591
TI - The role of HE4 for prediction of recurrence in epithelial ovarian cancer
patients-results from the OVCAD study.
AB - Patients with epithelial ovarian cancer (EOC) are at high risk of tumor
recurrence. Human epididymis protein 4 (HE4) has been shown to be overexpressed
in EOC. The primary aim of our study was to evaluate the role of HE4 in
predicting recurrence in EOC patients. Furthermore, we assessed the role of HE4
in predicting recurrence after second-line chemotherapy. We retrospectively
analyzed data of 92 out of 275 primary EOC patients of the multicenter project
"Ovarian Cancer: Diagnosis of a silent killer" (OVCAD). The concentrations of HE4
and CA125 were determined preoperatively and 6 months after the end of platinum
based first-line chemotherapy (FU) using ELISA and Luminex technique,
respectively. The role of HE4 and CA125 for prediction of recurrence was
determined using receiver operating characteristics (ROC) curves. Out of 92
patients included, 70 (76 %) were responders and 22 (23 %) non-responders in
terms of response to platinum-based first-line chemotherapy. Median HE4
concentrations at follow-up (FU) differed between responders and non-responders
(60.5 vs. 237.25 pM, p = 0.0001), respectively. The combined use of HE4 and CA125
at FU with cut-off values of 49.5 pM and 25 U/ml for HE4 and CA125, respectively,
for predicting recurrence within 12 months after first-line chemotherapy
performed better than HE4 or CA125 alone (area under the curve (AUC) 0.928, 95 %
confidence intervals (CI) 0.838-1, p < 0.001). HE4 at FU could predict recurrence
within 6 months after second-line chemotherapy (AUC 0.719, 95 % CI 0.553-0.885, p
= 0.024). The combination of both elevated biomarkers revealed significantly
worse estimated median progression-free survival (PFS; hazard ratio (HR) 8.14, 95
% CI 3.75-17.68, p < 0.001) and slightly worse PFS in those in whom only one
biomarker was elevated (HR 1.46, 95 % CI 0.72-2.96, p = 0.292) compared to those
patients in whom no biomarker was elevated. For the estimated median overall
survival (OS), our analysis revealed similar results. HE4 in combination with
CA125 performed better than CA125 and HE4 alone in predicting recurrence within
12 months after first-line chemotherapy.
PMID- 26419592
TI - Developing strategies to predict photodynamic therapy outcome: the role of
melanoma microenvironment.
AB - Melanoma is among the most aggressive and treatment-resistant human skin cancer.
Photodynamic therapy (PDT), a minimally invasive therapeutic modality, is a
promising approach to treating melanoma. It combines a non-toxic photoactivatable
drug called photosensitizer with harmless visible light to generate reactive
oxygen species which mediate the antitumor effects. The aim of this review was to
compile the available data about PDT on melanoma. Our comparative analysis
revealed a disconnection between several hypotheses generated by in vitro
therapeutic studies and in vivo and clinical assays. This fact led us to
highlight new preclinical experimental platforms that mimic the complexity of
tumor biology. The tumor and its stromal microenvironment have a dynamic and
reciprocal interaction that plays a critical role in tumor resistance, and these
interactions can be exploited for novel therapeutic targets. In this sense, we
review two strategies used by photodynamic researchers: (a) developing 3D culture
systems which mimic tumor architecture and (b) heterotypic cultures that resemble
tumor microenvironment to favor therapeutic regimen design. After this
comprehensive review of the literature, we suggest that new complementary
preclinical models are required to better optimize the clinical outcome of PDT on
skin melanoma.
PMID- 26419594
TI - BMP10 inhibited the growth and migration of gastric cancer cells.
AB - Bone morphogenetic protein 10 (BMP10), a novel member of BMP family, has been
identified as an important regulator for angiogenesis. Dysregulation of BMP has
been observed in several cancer types. However, its roles in gastric cancer (GC)
remain unknown. In this study, the expression of BMP10 was found to be down
regulated in GC samples. Forced expression of BMP10 in GC cells inhibited its
growth and migration, while knocking down the expression of BMP10 in GC cells
promoted cell growth, migration, and metastasis. BMP10 was shown to negatively
regulated beta-catenin/TCF signaling by up-regulating Axin protein level. Taken
together, the present study revealed the suppressive function of BMP10 in gastric
cancer.
PMID- 26419593
TI - Antimetastatic effect of fluvastatin on breast and hepatocellular carcinoma cells
in relation to SGK1 and NDRG1 genes.
AB - Metastasis occurs due to migration of the cells from primary tumor toward other
tissues by gaining invasive properties. Since metastatic invasion shows a strong
resistance against conventional cancer treatments, the studies on this issue have
been focused. Within this context, inhibition of migration and determination of
the relationships at the gene level will contribute to treatment of metastatic
cancer cases. We have aimed to demonstrate the impact of TGF-beta1 and
fluvastatin on human breast cancer (MCF-7) and human hepatocellular carcinoma
(Hep3B) cell cultures via Real-Time Cell Analyzer (RTCA) and to test the
expression levels of some genes (NDRG1, SGK1, TWIST1, AMPKA2) and to compare
their gene expression levels according to RTCA results. Both of cell series were
applied TGF-beta1 and combinations of TGF-beta1/fluvastatin. Primer and probes
were synthesized using Universal Probe Library (UPL, Roche) software, and
expression levels of genes were tested via qPCR using the device LightCycler 480
II (Roche). Consequently, fluvastatin dose-dependently inhibited migration
induced by TGF-beta1 in both groups. This inhibition was accompanied by low level
of SGK1 messenger RNA (mRNA) and high levels of NDRG1 and AMPKA2 mRNA. Thus, we
conclude that fluvastatin plays an important role in reducing resistance to
chemotherapeutics and preventing metastasis.
PMID- 26419595
TI - Analgesic-antitumor peptide inhibits the migration and invasion of HepG2 cells by
an upregulated VGSC beta1 subunit.
AB - Analgesic-antitumor peptide (AGAP), one of the scorpion toxin polypeptides, has
been shown to have an antitumor activity. Recombinant AGAP (rAGAP) was shown to
affect the migration and invasion of HepG2 cells via a voltage-gated sodium
channel (VGSC) beta1 subunit. The VGSC beta1 subunit was validated as a cell
adhesion molecule (CAM) in human hepatocellular carcinoma (HCC) cell lines. rAGAP
suppresses the migration and invasion of HepG2 cells but has no significant
effect of human liver HL7702 cells without beta1 subunit expression. rAGAP
inhibits the migration and invasion of the cells when the VGSC beta1 subunit is
overexpressed in HL7702 cells. To explain these findings, VGSC beta1 subunit
messenger RNA (mRNA) and protein levels were measured. The beta1 subunit protein
level was upregulated in a dose-dependent manner following treatment with rAGAP
while there was no significant change in the mRNA level, so rAGAP might be an
active component of the VGSC beta1 subunit.
PMID- 26419596
TI - Altered serum fatty acid composition in geriatric depression.
AB - Fatty acids (FA), mainly polyunsaturated (PUFA) of n-3 or n-6 types, may
influence neuropsychobiological processes. Decreased levels of n-3 PUFA have been
shown to be related to major depression and supplementation of n-3 PUFA seems to
contribute to improved depression treatment outcome. The profiles of serum FA
profiles in patients with geriatric depression have not been thoroughly studied
yet. The present study investigated the FA profiles of patients with geriatric
depression and of mentally healthy elderly individuals. Serum FA profiles of 36
inpatients with geriatric depression who fulfilled DSM-IV criteria for unipolar
major depression were compared with those of 37 control subjects. Patients with
geriatric depression, irrespective of gender, exhibited lower total FAs, as well
as significantly lower concentrations of total n-3 PUFA and eicosapentaenoic
acid, though the groups did not differ with regard to Body Mass Index. The
findings of the present study point to an association between lower FA serum
levels and geriatric depression. Further investigations with larger samples and
dietetic interventions may provide deeper insights into the role of
eicosapentaenoic acid and total n-3 PUFA in the development and treatment of
geriatric depression.
PMID- 26419599
TI - Polarizable Force Field with a sigma-Hole for Liquid and Aqueous Bromomethane.
AB - Bromomethane (CH3Br) is an acutely toxic environmental pollutant that contributes
to ozone depletion. Molecular simulation could be a valuable tool for studying
its partitioning and transport in the environment if an accurate molecular model
was available. The generalized Amber force field (GAFF), OPLS (optimized
potentials for liquid simulations) force field, and CHARMM general force field
(CGenFF) were tested for their ability to model the physical properties of liquid
bromomethane. The OPLS force field was in fairly good agreement with experiment,
while CGenFF and GAFF were significantly in error. The Br Lennard-Jones
parameters of the GAFF and CGenFF models were reparameterized, but their radial
distribution functions still have significant deviations from those calculated by
ab initio molecular dynamics (AIMD). A Drude polarizable force field for
bromomethane was parametrized with an off-center positively charged site to
represent the C-Br sigma-hole. This model is in good agreement with the bulk
physical properties and the AIMD RDFs. The modest solubility of bromomethane was
reproduced by this model, with dispersion interactions being the dominant water
solute interaction. The water-solute electrostatic interactions are a smaller
factor in solubility. This model predicts bromomethane to have a 13 kJ mol(-1)
surface excess potential at the water-vapor interface.
PMID- 26419597
TI - Driving and attention deficit hyperactivity disorder.
AB - Adults with attention deficit hyperactivity disorder (ADHD) suffer from various
impairments of cognitive, emotional and social functioning, which can have
considerable consequences for many areas of daily living. One of those areas is
driving a vehicle. Driving is an important activity of everyday life and requires
an efficient interplay between multiple cognitive, perceptual, and motor skills.
In the present study, a selective review of the literature on driving-related
difficulties associated with ADHD is performed, seeking to answer whether
individuals with ADHD show increased levels of unsafe driving behaviours, which
cognitive (dys)functions of individuals with ADHD are related to driving
difficulty, and whether pharmacological treatment significantly improves the
driving behaviour of individuals with ADHD. The available research provides
convincing evidence that individuals with ADHD have different and more adverse
driving outcomes than individuals without the condition. However, it appears that
not all individuals with ADHD are affected uniformly. Despite various cognitive
functions being related with driving difficulties, these functions do not appear
helpful in detecting high risk drivers with ADHD, nor in predicting driving
outcomes in individuals with ADHD, since impairments in these functions are
defining criteria for the diagnoses of ADHD (e.g., inattention and impulsivity).
Pharmacological treatment of ADHD, in particular stimulant drug treatment,
appears to be beneficial to the driving difficulties experienced by individuals
with ADHD. However, additional research is needed, in particular further studies
that address the numerous methodological weaknesses of many of the previous
studies.
PMID- 26419598
TI - Molecular diversity of spirooxindoles. Synthesis and biological activity.
AB - Spirooxindoles are important synthetic targets possessing extended biological
activity and drug discovery applications. This review focuses on the various
strategies for the enantioselective synthesis of spirocyclic oxindoles relying on
reports over the past decade and from earlier work. The spirooxindoles in this
review are separated into three structural classes, and then further categorized
into the method type from which the spirocycle is generated.
PMID- 26419600
TI - Commonly-occurring polymorphisms in the COMT, DRD1 and DRD2 genes influence
different aspects of motor sequence learning in humans.
AB - Performing sequences of movements is a ubiquitous skill that involves dopamine
transmission. However, it is unclear which components of the dopamine system
contribute to which aspects of motor sequence learning. Here we used a genetic
approach to investigate the relationship between different components of the
dopamine system and specific aspects of sequence learning in humans. In
particular, we investigated variations in genes that code for the catechol-O
methyltransferase (COMT) enzyme, the dopamine transporter (DAT) and dopamine D1
and D2 receptors (DRD1 and DRD2). COMT and the DAT regulate dopamine availability
in the prefrontal cortex and the striatum, respectively, two key regions
recruited during learning, whereas dopamine D1 and D2 receptors are thought to be
involved in long-term potentiation and depression, respectively. We show that
polymorphisms in the COMT, DRD1 and DRD2 genes differentially affect behavioral
performance on a sequence learning task in 161 Caucasian participants. The DRD1
polymorphism predicted the ability to learn new sequences, the DRD2 polymorphism
predicted the ability to perform a previously learnt sequence after performing
interfering random movements, whereas the COMT polymorphism predicted the ability
to switch flexibly between two sequences. We used computer simulations to explore
potential mechanisms underlying these effects, which revealed that the DRD1 and
DRD2 effects are possibly related to neuroplasticity. Our prediction-error
algorithm estimated faster rates of connection strengthening in genotype groups
with presumably higher D1 receptor densities, and faster rates of connection
weakening in genotype groups with presumably higher D2 receptor densities.
Consistent with current dopamine theories, these simulations suggest that D1
mediated neuroplasticity contributes to learning to select appropriate actions,
whereas D2-mediated neuroplasticity is involved in learning to inhibit incorrect
action plans. However, the learning algorithm did not account for the COMT
effect, suggesting that prefrontal dopamine availability might affect sequence
switching via other, non-learning, mechanisms. These findings provide insight
into the function of the dopamine system, which is relevant to the development of
treatments for disorders such as Parkinson's disease. Our results suggest that
treatments targeting dopamine D1 receptors may improve learning of novel
sequences, whereas those targeting dopamine D2 receptors may improve the ability
to initiate previously learned sequences of movements.
PMID- 26419601
TI - Yolk hormones influence in ovo chemosensory learning, growth, and feeding
behavior in domestic chicks.
AB - In this study, we assessed whether prenatal exposure to elevated yolk steroid
hormones can influence in ovo chemosensory learning and the behavior of domestic
chicks. We simulated a maternal environmental challenge by experimentally
enhancing yolk progesterone, testosterone, and estradiol concentrations in hen
eggs prior to incubation. The embryos from these hormones-treated eggs (HO) as
well as sham embryos (O) that had received the vehicle-only were exposed to the
odor of fish oil (menhaden) between embryonic Days 11 and 20. An additional group
of control embryos (C) was not exposed to the odor. All chicks were tested
following hatching for their feeding preferences between foods that were or were
not odorized with the menhaden odor. In the 3-min choice tests, the behavior of O
chicks differed significantly according to the type of food whereas C and HO
chicks showed no preference between odorized and non-odorized food. Our result
suggests weaker response in HO chicks. In addition, HO chicks showed impaired
growth and reduced intake of an unfamiliar food on the 24-h time scale compared
to controls. Our data suggest that embryonic exposure to increased yolk hormone
levels can alter growth, chemosensory learning, and the development of feeding
behaviors.
PMID- 26419604
TI - A novel astrovirus species in the gut of yaks with diarrhoea in the Qinghai
Tibetan Plateau, 2013.
AB - The yak (Bos grunniens) is an iconic symbol in the high-altitude region of the
Qinghai-Tibetan Plateau. Diarrhoea is a common disease in yaks, resulting in
major economic losses. To investigate the diversity of viral species, we reported
the metagenomics-derived virome in a pooled faecal sample of 20 diarrhoeic yaks.
The nine viruses found in the pooled diarrhoeic samples, in order of abundance of
nucleic acid sequence, were influenza A virus, bovine viral diarrhoea virus
(BVDV), rotavirus, ungulate tetraparvovirus 1 (bovine hokovirus), astrovirus
(AstV), bovine enterovirus, hepatitis E virus, kobuvirus and woodchuck hepatitis
virus. Compared with healthy yaks, only AstV had a significantly higher
prevalence rate in diarrhoeal samples, indicating a correlation with the clinical
symptoms of diarrhoea in yaks. To further investigate the molecular
characterization of yak AstV, a near-full genome was obtained from a diarrhoeic
sample. It was 6243 bp in length and shared 46.4-66.2 % similarity with other
related bovine AstVs from faeces. Phylogenetic analysis of the genome
demonstrated that the yak AstV fell within the bovine AstVs cluster, but was
located in a unique lineage, suggesting a novel AstV species was identified in
yaks. Interestingly, the ORF2 region of yak AstV had closer similarity and
genetically relationship with deer AstV strain CcAstV-2 than that of the bovine
AstVs. Further analysis showed that one possible interspecies recombination event
occurred in ORF2. In summary, this study expanded our understanding of the viral
communities of diarrhoeal yaks and identified a novel AstV that was associated
with diarrhoea in yaks.
PMID- 26419602
TI - Platelets and plasma stimulate sheep rotator cuff tendon tenocytes when cultured
in an extracellular matrix scaffold.
AB - The addition of platelet-rich plasma (PRP) to rotator cuff repair has not
translated into improved outcomes after surgery. However, recent work stimulating
ligament healing has demonstrated improved outcomes when PRP or whole blood is
combined with an extracellular matrix carrier. The objective of this study was to
evaluate the effect of three components of blood (plasma, platelets, and
macrophages) on the in vitro activity of ovine rotator cuff cells cultured in an
extracellular matrix environment. Tenocytes were obtained from six ovine
infraspinatus tendons and cultured over 14 days in an extracellular matrix
scaffold with the following additives: (1) plasma (PPP), (2) plasma and platelets
(PAP), (3) plasma and macrophages (PPPM), (4) plasma, platelets and macrophages
(PAPM), (5) phosphate buffered saline (PBS), and (6) PBS with macrophages (PBSM).
Assays measuring cellular metabolism (AlamarBlue), proliferation (Quantitative
DNA assay), synthesis of collagen and cytokines (SIRCOL, TNF-alpha and IL-10
ELISA, and MMP assay), and collagen gene expression (qPCR) were performed over
the duration of the experiment, as well as histology at the conclusion. Plasma
was found to stimulate cell attachment and spreading on the scaffold, as well as
cellular proliferation. Platelets also stimulated cell proliferation, cellular
metabolism, transition of cells to a myofibroblast phenotype, and contraction of
the scaffolds. The addition of macrophages did not have any significant effect on
the sheep rotator cuff cells in vitro. In vivo studies are needed to determine
whether these changes in cellular function will translate into improved tendon
healing.
PMID- 26419605
TI - Reliability and validity of the Nurse Practitioners' Roles and Competencies
Scale.
AB - AIMS AND OBJECTIVES: The objective of this study was to test the reliability and
construct validity of the Nurse Practitioners' Roles and Competencies Scale.
BACKGROUND: The role of nurse practitioners has attracted international
attention. The advanced nursing role played by nurse practitioners varies with
national conditions and medical environments. To date, no suitable measurement
tool has been available for assessing the roles and competencies of nurse
practitioners in Asian countries. DESIGN: Secondary analysis of data from three
studies related to nurse practitioners' role competencies. METHODS: We analysed
data from 563 valid questionnaires completed in three studies to identify the
factor structure of the Nurse Practitioners' Roles and Competencies Scale. To
this end, we performed exploratory factor analysis using principal component
analysis extraction with varimax orthogonal rotation. The internal consistency
reliabilities of the overall scale and its subscales were examined using
Cronbach's alpha coefficient. RESULTS: The scale had six factors:
professionalism, direct care, clinical research, practical guidance, medical
assistance, as well as leadership and reform. These factors explained 67.5% of
the total variance in nurse practitioners' role competencies. Cronbach's alpha
coefficient for the overall scale was 0.98, and those of its subscales ranged
from 0.83-0.97. CONCLUSION: The internal consistency reliability and construct
validity of the Nurse Practitioners' Roles and Competencies Scale were good. The
high internal consistency reliabilities suggest item redundancy, which should be
minimised by using item response theory to enhance the applicability of this
questionnaire for future academic and clinical studies. RELEVANCE TO CLINICAL
PRACTICE: The Nurse Practitioners' Roles and Competencies Scale can be used as a
tool for assessing the roles and competencies of nurse practitioners in Taiwan.
Our findings can also serve as a reference for other Asian countries to develop
the nurse practitioner role.
PMID- 26419606
TI - Maternal nutritional status (as measured by height, weight and BMI) in
Bangladesh: trends and socio-economic association over the period 1996 to 2007.
AB - OBJECTIVE: To analyse trends in maternal nutritional status in Bangladesh over a
12-year period and to examine the associations between nutritional status and
socio-economic variables. DESIGN: Maternal nutritional status indicators were
height, weight and BMI. Socio-economic variables used were region, residency,
education and occupation of the mothers and their husbands, house type, and
possession score in the household. SETTING: Bangladesh Demographic and Health
Surveys (1996, 2000, 2004 and 2007) were the source of data. SUBJECTS: A total of
16 278 mothers were included. RESULTS: All of the socio-economic variables showed
significant associations with maternal nutritional status indicators. Regional
variation was found to be present; all three indicators were found to be lowest
in the Sylhet division. Upward trends in maternal height, weight and BMI were
evident from no possessions to four possessions in households, and for no
education to higher education of women and their husbands. Bangladeshi mothers
measured in 2007 were found to be on average 0.34 cm taller and 3.36 kg heavier
than mothers measured in 1996. Between 1996 and 2007 maternal underweight fell
from nearly 50 % to just over 30 % while overweight and obesity increased from
about 3 % to over 9 % (WHO cut-offs) or from 7 % to nearly 18 % (Asian cut-offs).
CONCLUSIONS: The study reveals that over the 12-year period in Bangladesh there
has been a substantial reduction in maternal underweight accompanied by a
considerable increase in obesity. It is also evident that malnutrition in
Bangladesh is a multidimensional problem that warrants a proper policy mix and
programme intervention.
PMID- 26419608
TI - Comparison of emission estimates for non-CO2 greenhouse gases from livestock and
poultry in Korea from 1990 to 2010.
AB - It has often been claimed that non-carbon dioxide greenhouse gases (NCGGs), such
as methane, nitrous oxide and fluorinated greenhouse gases, are significant
contributors to climate change. Here we nvestigate emission estimates of methane
and nitrous oxide from livestock and poultry production, which is recognized as a
major source of those NCGGs, in Korea over the period of 1990 through 2010. Based
on the data on livestock and poultry populations, emission estimates of methane
and nitrous oxide are first derived based on the Tier 1 approach. Then, the Tier
2 approach is adopted to obtain emission estimates of methane and nitrous oxide
from cattle, which are known to be the largest sources of these NCGGs and account
for about 70% of emissions from livestock and poultry in Korea. The result
indicates that the Tier 2 estimates of methane and nitrous oxide emissions from
enteric fermentation and manure management are significantly different from the
Tier 1 estimates over the analysis period.
PMID- 26419607
TI - Inhibition of Beta-Amyloid Fibrillation by Luminescent Iridium(III) Complex
Probes.
AB - We report herein the application of kinetically inert luminescent iridium(III)
complexes as dual inhibitors and probes of beta-amyloid fibrillogenesis. These
iridium(III) complexes inhibited Abeta1-40 peptide aggregation in vitro, and
protected against Abeta-induced cytotoxicity in neuronal cells. Furthermore, the
complexes differentiated between the aggregated and unaggregated forms of Abeta1
40 peptide on the basis of their emission response.
PMID- 26419610
TI - BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating
KLF5.
AB - The transcription factor KLF5 is highly expressed in basal-like breast cancer and
promotes breast cancer cell proliferation, survival, migration and tumour growth.
Here we show that, in breast cancer cells, KLF5 is stabilized by the
deubiquitinase (DUB) BAP1. With a genome-wide siRNA library screen of DUBs, we
identify BAP1 as a bona fide KLF5 DUB. BAP1 interacts directly with KLF5 and
stabilizes KLF5 via deubiquitination. KLF5 is in the BAP1/HCF-1 complex, and this
newly identified complex promotes cell cycle progression partially by inhibiting
p27 gene expression. Furthermore, BAP1 knockdown inhibits tumorigenicity and lung
metastasis, which can be rescued partially by ectopic expression of KLF5.
Collectively, our findings not only identify BAP1 as the DUB for KLF5, but also
reveal a critical mechanism that regulates KLF5 expression in breast cancer. Our
findings indicate that BAP1 could be a potential therapeutic target for breast
and other cancers.
PMID- 26419611
TI - Post-movement processing in visual oddball task - Evidence from intracerebral
recording.
AB - OBJECTIVE: To identify intracerebral sites activated after correct motor response
during cognitive task and to assess associations of this activity with mental
processes. METHODS: Intracerebral EEG was recorded from 205 sites of frontal,
temporal and parietal lobes in 18 epileptic patients, who responded by button
pressing together with mental counting to target stimuli in visual oddball task.
RESULTS: Post-movement event-related potentials (ERPs) with mean latency 295 +/-
184 ms after movement were found in all subjects in 64% of sites investigated.
Generators were consistently observed in mesiotemporal structures, anterior
midcingulate, prefrontal, and temporal cortices. Task-variant nonspecific and
target specific post-movement ERPs were identified, displaying no significant
differences in distribution among generating structures. Both after correct and
incorrect performances the post-performance ERPs were observed in frontal and
temporal cortices with latency sensitive to error commission in several frontal
regions. CONCLUSION: Mesiotemporal structures and regions in anterior
midcingulate, prefrontal and temporal cortices seem to represent integral parts
of network activated after correct motor response in visual oddball task with
mental counting. Our results imply equivalent involvement of these structures in
task-variant nonspecific and target specific processes, and suggest existence of
common nodes for correct and incorrect responses. SIGNIFICANCE: Our results
contribute to better understanding of neural mechanisms underlying goal-directed
behavior.
PMID- 26419612
TI - Bradysomnia in Parkinson's disease.
AB - OBJECTIVE: Polysomnography studies in Parkinson's disease (PD) patients show
altered sleep microstructure with decreased level of arousability, indicating
impaired sleep-wake dynamics in PD. The aim of this study was to investigate
dynamical aspects of sleep EEG in PD as compared to healthy controls. METHODS: In
this retrospective, controlled study, we applied a previously established
mathematical model of sleep EEG analysis (state space model) to PD patients and
age- and gender-matched healthy volunteers (N=64). Dynamical aspects of sleep
were quantified by measuring the spectral variability of the sleep EEG (by means
of state space velocity). RESULTS: State space analysis revealed preserved global
sleep-wake architecture in PD patients, but the velocity of sleep stage
transitions was significantly reduced as compared to healthy controls.
Correlation analysis revealed a strong association of state space velocity with
arousal scores and daily dopamine agonist intake. CONCLUSIONS: Quantitative
analysis of spectral sleep EEG variability (state space velocity) revealed
reduced sleep-wake dynamics in PD patients as compared to control subjects.
SIGNIFICANCE: We propose state space velocity as an objective and quantitative
measure for altered sleep microstructure and as a potential biomarker of sleep
alterations in PD, not accessible by conventional sleep analysis.
PMID- 26419613
TI - Donor Properties of a New Class of Guanidinate Ligands Possessing Ketimine
Backbones: A Comparative Study Using Iron.
AB - Addition of 1 equiv of LiN?C(t)Bu2 or LiN?Ad (Ad = 2-adamantyl) to the aryl
carbodiimide C(NDipp)2 (Dipp = 2,6-diisopropylphenyl) readily generates the
lithium ketimine-guanidinates Li(THF)2[(X)C(NDipp)2] (X = N?C(t)Bu2 (1-(t)Bu),
N?Ad (1-Ad)) in excellent yields. These new ligands can be readily metalated with
iron to give the N,N'-bidentate chelates [{(X)C(NDipp)2}FeBr]2 (X = N?C(t)Bu2 (5
(t)Bu), N?Ad (5-Ad)), in which the ketimines behave as noncoordinating backbone
substituents. In an effort to understand the potential electronic contributions
of the ketimine group to the ligand architecture, a thorough structural and
electronic study was conducted comparing the features and properties of 5-(t)Bu
and 5-Ad to their guanidinate and amidinate analogues [{(X)C(NDipp)2}FeBr]2 (X =
(i)Pr2N (6), (t)Bu (7)). Solid-state structural analyses indicate little
electronic contribution from the N-ketimine nitrogen atom, while solution-phase
electronic absorption spectra of 5-(t)Bu and 5-Ad are qualitatively similar to
the amidinate complex 7. Yet, electrochemical measurements do show the donor
properties of the ketimine-guanidinate in 5-(t)Bu to be intermediate between its
guanidinate and amidinate counterparts in 6 and 7. Preliminary reactivity studies
also show that the reduction chemistry of 5-(t)Bu diverges significantly from
that of 6 and 7. Treatment of 5-(t)Bu with excess magnesium or 1 equiv of KC8
leads to the formation of the Fe(I)-Fe(I) complex [{MU-((t)Bu2C?N)C(NDipp)2}2Fe2]
(11), which possesses an exceedingly short Fe?Fe bond (2.1516(5) A), while
neither 6 nor 7 forms dinuclear complexes upon reduction. This result
demonstrates that ketimine-guanidinates do not simply behave as amidinate
variants but can contribute to distinctive metal chemistry of their own.
PMID- 26419614
TI - Phase diagrams of dune shape and orientation depending on sand availability.
AB - New evidence indicates that sand availability does not only control dune type but
also the underlying dune growth mechanism and the subsequent dune orientation.
Here we numerically investigate the development of bedforms in bidirectional wind
regimes for two different conditions of sand availability: an erodible sand bed
or a localized sand source on a non-erodible ground. These two conditions of sand
availability are associated with two independent dune growth mechanisms and, for
both of them, we present the complete phase diagrams of dune shape and
orientation. On an erodible sand bed, linear dunes are observed over the entire
parameter space. Then, the divergence angle and the transport ratio between the
two winds control dune orientation and dynamics. For a localized sand source,
different dune morphologies are observed depending on the wind regime. There are
systematic transitions in dune shape from barchans to linear dunes extending away
from the localized sand source, and vice-versa. These transitions are captured
fairly by a new dimensionless parameter, which compares the ability of winds to
build the dune topography in the two modes of dune orientation.
PMID- 26419615
TI - A typology of people who tamper with pharmaceutical opioids: responses to
introduction of a tamper-resistant formulation of controlled-release oxycodone.
AB - PURPOSE: In April 2014, a tamper-resistant controlled-release oxycodone
formulation was released in Australia. We aimed to determine whether there are
latent classes of people who tamper with pharmaceutical opioids based on
frequency of opioid and illicit drug use, the demographic and clinical profiles
of these groups, and if there were changes in use and harms following the
introduction. METHODS: A prospective cohort of 606 people who regularly tamper
with pharmaceutical opioids was interviewed January to March 2014 (Wave 1) and
May to August 2014 (Wave 2). Latent class analysis identified groups based on non
prescribed opioid, illicit drug and prescribed opioid substitution therapy (OST)
use at Wave 1. Regression models examined whether group membership predicted use
and harms at Wave 2. RESULTS: Four groups were identified: frequent OST group
(39%), mixed OST/heroin group (7%), infrequent pharmaceutical opioid and heroin
group (44%) and frequent oxycodone group (25%). Compared with the frequent OST
group, the infrequent pharmaceutical opioid/heroin group was more likely to
report non-everyday pain and risky alcohol use, and the frequent oxycodone group
had higher odds of homelessness. At Wave 2, oxycodone use decreased across groups
(odds ratios (OR) <= 0.18, p < 0.001, particularly for the frequent oxycodone
group: OR <= 0.05, p < 0.001), with reductions in days of use (g >= 0.35, p <
0.050). Non-prescribed pharmaceutical opioid use, illicit drug use and harms
remained stable or decreased. CONCLUSIONS: Despite heterogeneity among people who
tamper with pharmaceutical opioids, the tamper-resistant formulation was followed
by reductions in oxycodone tampering among high-frequency and low-frequency
users. There was no evidence of increased use of other opioids or illicit drugs.
PMID- 26419616
TI - An unusually simple HP1 gene set in Hymenopteran insects.
AB - The heterochromatin protein 1 (HP1) gene family includes a set of paralogs in
higher eukaryotes that serve fundamental roles in heterochromatin structure and
maintenance, and other chromatin-related functions. At least 10 full and 16
partial HP1 genes exist among Drosophila species, with multiple gene gains,
losses, and sub-functionalizations within this insect group. An important
question is whether this diverse set of HP1 genes and their dynamic evolution
represent the standard rule in eukaryotic groups. Here we have begun to address
this question by bio-informatically identifying the HP1 family genes in
representative species of the insect order Hymenoptera, which includes all ants,
bees, wasps, and sawflies. Compared to Drosophila species, Hymenopterans have a
much simpler set of HP1 genes, including one full and two partial HP1s. All 3
genes appear to have been present in the common ancestor of the Hymenopterans and
they derive from a Drosophila HP1B-like gene. In ants, a partial HP1 gene
containing only a chromoshadow domain harbors amino acid changes at highly
conserved sites within the PxVxL recognition region, suggesting that this gene
has undergone sub-functionalization. In the jewel wasp Nasonia vitripennis, the
full HP1 and partial chromoshadow-only HP1 are expressed in both germ line and
somatic tissues. However, the partial chromodomain-only HP1 is expressed
exclusively in the ovary and testis, suggesting that it may have a specialized
chromatin role during gametogenesis. Our findings demonstrate that the HP1 gene
family is much simpler and evolutionarily less dynamic within the Hymenopterans
compared to the much younger Drosophila group, a pattern that may reflect major
differences in the range of chromatin-related functions present in these and
perhaps other insect groups.
PMID- 26419617
TI - Involvement of Notch-1 in Resistance to Regorafenib in Colon Cancer Cells.
AB - Regorafenib, an oral small-molecule multi kinase inhibitor, is able to block
Vascular Endothelial Growth Factor Receptors (VEGFR-1, 2, and 3), Platelet
Derived Growth Factor Receptors (PDGF), Fibroblast Growth Factor (FGF) receptor
1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. Different studies have
displayed its antitumor activity in several cancer models (both in vitro and in
vivo), particularly in colorectal and gastrointestinal stromal cancers. The
mechanism of resistance to regorafenib is largely unknown. In our investigation,
we have generated regorafenib-resistant SW480 cells (Reg-R-SW480 cells) by
culturing such cells with increasing concentration of regorafenib. Examination of
intracellular signaling found that Akt signaling was activated in Reg-R-SW480
cells but not in wild-type SW480 cells, after regorafenib treatment as measured
by Western Blot. The Notch pathway is a fundamental signaling system in the
development and homeostasis of tissues since it regulates different cellular
process such as proliferation, differentiation, and apoptosis and it can be a
potential driver of resistance to a wide array of targeted therapies. In this
study, we found that Notch-1 was significantly up-regulated in resistant tumor
cells as well as HES1 and HEY. Additionally, inhibition of Notch-1 in resistant
cells partially restored sensitivity to regorafenib treatment in vitro.
Collectively, these data suggest a key role of Notch-1 in mediating the resistant
effects of regorafenib in colorectal cancer cells, and also provide a rationale
to improve the therapeutic efficacy of regorafenib.
PMID- 26419618
TI - ZnO@SnO2 engineered composite photoanodes for dye sensitized solar cells.
AB - Layered multi-oxide concept was applied for fabrication of photoanodes for dye
sensitized solar cells based on ZnO and SnO2, capitalizing on the beneficial
properties of each oxide. The effect of different combinations of ZnO@SnO2 layers
was investigated, aimed at exploiting the high carrier mobility provided by the
ZnO and the higher stability under UV irradiation pledged by SnO2. Bi-oxide
photoanodes performed much better in terms of photoconversion efficiency (PCE)
(4.96%) compared to bare SnO2 (1.20%) and ZnO (1.03%). Synergistic cooperation is
effective for both open circuit voltage and photocurrent density: enhanced values
were indeed recorded for the layered photoanode as compared with bare oxides (Voc
enhanced from 0.39 V in case of bare SnO2 to 0.60 V and Jsc improved from 2.58
mA/cm(2) pertaining to single ZnO to 14.8 mA/cm(2)). Improved functional
performances of the layered network were ascribable to the optimization of both
high chemical capacitance (provided by the SnO2) and low recombination resistance
(guaranteed by ZnO) and inhibition of back electron transfer from the SnO2
conduction band to the oxidized species of the electrolyte. Compared with
previously reported results, this study testifies how a simple electrode design
is powerful in enhancing the functional performances of the final device.
PMID- 26419619
TI - Predicting time to castration resistance in hormone sensitive prostate cancer by
a personalization algorithm based on a mechanistic model integrating patient
data.
AB - BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer death of men
worldwide. In hormone-sensitive prostate cancer (HSPC), androgen deprivation
therapy (ADT) is widely used, but an eventual failure on ADT heralds the passage
to the castration-resistant prostate cancer (CRPC) stage. Because predicting time
to failure on ADT would allow improved planning of personal treatment strategy,
we aimed to develop a predictive personalization algorithm for ADT efficacy in
HSPC patients. METHODS: A mathematical mechanistic model for HSPC progression and
treatment was developed based on the underlying disease dynamics (represented by
prostate-specific antigen; PSA) as affected by ADT. Following fine-tuning by a
dataset of ADT-treated HSPC patients, the model was embedded in an algorithm,
which predicts the patient's time to biochemical failure (BF) based on clinical
metrics obtained before or early in-treatment. RESULTS: The mechanistic model,
including a tumor growth law with a dynamic power and an elaborate ADT-resistance
mechanism, successfully retrieved individual time-courses of PSA (R(2) = 0.783).
Using the personal Gleason score (GS) and PSA at diagnosis, as well as PSA
dynamics from 6 months after ADT onset, and given the full ADT regimen, the
personalization algorithm accurately predicted the individual time to BF of ADT
in 90% of patients in the retrospective cohort (R(2) = 0.98). CONCLUSIONS: The
algorithm we have developed, predicting biochemical failure based on routine
clinical tests, could be especially useful for patients destined for short-lived
ADT responses and quick progression to CRPC. Prospective studies must validate
the utility of the algorithm for clinical decision-making.
PMID- 26419620
TI - Evaluating attention in delirium: A comparison of bedside tests of attention.
AB - AIM: Impaired attention is a core diagnostic feature for delirium. The present
study examined the discriminating properties for patients with delirium versus
those with dementia and/or no neurocognitive disorder of four objective tests of
attention: digit span, vigilance "A" test, serial 7s subtraction and months of
the year backwards together with global clinical subjective rating of attention.
METHODS: This as a prospective study of older patients admitted consecutively in
a general hospital. Participants were assessed using the Confusion Assessment
Method, Delirium Rating Scale-98 Revised and Montreal Cognitive Assessment
scales, and months of the year backwards. Pre-existing dementia was diagnosed
according to the Diagnostic and Statistical Manual of Mental Disorders fourth
edition criteria. RESULTS: The sample consisted of 200 participants (mean age
81.1 +/- 6.5 years; 50% women; pre-existing cognitive impairment in 126 [63%]). A
total of 34 (17%) were identified with delirium (Confusion Assessment Method +).
The five approaches to assessing attention had statistically significant
correlations (P < 0.05). Discriminant analysis showed that clinical subjective
rating of attention in conjunction with the months of the year backwards had the
best discriminatory ability to identify Confusion Assessment Method-defined
delirium, and to discriminate patients with delirium from those with dementia
and/or normal cognition. Both of these approaches had high sensitivity, but
modest specificity. CONCLUSION: Objective tests are useful for prediction of non
delirium, but lack specificity for a delirium diagnosis. Global attentional
deficits were more indicative of delirium than deficits of specific domains of
attention. Geriatr Gerontol Int 2016; 16: 1028-1035.
PMID- 26419621
TI - Dynamic DNA architectures: spontaneous DNA strand exchange and self-sorting
driven by perylene bisimide interactions.
AB - Three differently bay-substituted perylene bisimides together with the
conventional unsubstituted chromophore were synthetically incorporated as
homodimers in DNA double strands. If preannealed DNA duplexes with two different
perylene bisimide homodimers are mixed together they undergo spontaneous DNA
strand exchange. The dynamic self-sorting forms DNA architectures preferentially
with perylene bisimide heterodimers and can be controlled by the electronic
density in the chromophores.
PMID- 26419622
TI - Revival of cytokine therapy in heart failure?
PMID- 26419623
TI - Vulnerable plaque imaging: updates on new pathobiological mechanisms.
AB - Early identification of vulnerable, rupture-prone atherosclerotic plaques with
the optimal goal of cardiovascular event prevention is a field of vigorous
research. Despite the advances in imaging modalities and the in vivo
identification of many characteristics of vulnerability, few of these plaques
actually rupture and even fewer lead to clinical events, questioning the
predictive value of the above techniques in clinical practice. Factors causing
the higher local vulnerability of the culprit plaque within a prothrombotic
environment of widespread inflammation are generally unknown. Newly recognized
local features, including microcalcifications and biomechanical factors, seem to
contribute. In this review article, we target on new mechanisms, implicated in
vulnerable plaque formation and rupture, analysing their potential clinical
value.
PMID- 26419624
TI - Genetic variants and disease: correlate or cause?
PMID- 26419625
TI - Atrial fibrillation in heart failure: what should we do?
AB - Heart failure (HF) and atrial fibrillation (AF) are two conditions that are
likely to dominate the next 50 years of cardiovascular (CV) care. Both are
increasingly prevalent and associated with high morbidity, mortality, and
healthcare cost. They are closely inter-related with similar risk factors and
shared pathophysiology. Patients with concomitant HF and AF suffer from even
worse symptoms and poorer prognosis, yet evidence-based evaluation and management
of this group of patients is lacking. In this review, we evaluate the common
mechanisms for the development of AF in HF patients and vice versa, focusing on
the evidence for potential treatment strategies. Recent data have suggested that
these patients may respond differently than those with HF or AF alone. These
results highlight the clear clinical need to identify and treat according to best
evidence, in order to prevent adverse outcomes and reduce the huge burden that HF
and AF are expected to have on global healthcare systems in the future. We
propose an easy-to-use clinical mnemonic to aid the initial management of newly
discovered concomitant HF and AF, the CAN-TREAT HFrEF + AF algorithm
(Cardioversion if compromised; Anticoagulation unless contraindication; Normalize
fluid balance; Target initial heart rate <110 b.p.m.; Renin-angiotensin
aldosterone modification; Early consideration of rhythm control; Advanced HF
therapies; Treatment of other CV disease).
PMID- 26419626
TI - CD1a+ survivin+ dendritic cell infiltration in dermal lesions of systemic
sclerosis.
AB - INTRODUCTION: Proto-oncogene survivin is a member of the inhibitor of apoptosis
(IAP) family of proteins. The presence of serous antibodies against survivin in
patients with systemic sclerosis has been previously reported; however, there are
few reports regarding the pathophysiological relationship between survivin and
systemic sclerosis. We herein investigated the expression and function of
survivin in SSc patients. METHODS: We performed immunohistochemistry analyses to
determine the expression of XIAP, cIAP and survivin in skin lesions from patients
with SSc and non-SSc. The expression levels of survivin in peripheral blood
mononuclear cells (PBMCs) obtained from SSc patients and healthy controls were
evaluated using RT-PCR and flow cytometry. Additionally, the function of survivin
was verified with overexpression experiments using monocyte-derived dendritic
cells (Mo-DCs). RESULTS: The expression patterns of both XIAP and cIAP were
similar, while only the survivin expression differed between the SSc and non-SSc
skin lesions. Survivin-overexpressing cells were detected in the SSc dermis
frequently. The positive rate of survivin in SSc dermis (64.3%, 9/14) was higher
than that in non-SSc dermis (11.2%, 1/9). Furthermore, survivin+ cells expressed
CD1a, one of the DC markers. Real-time PCR and FACS analyses revealed that the
survivin-WT (wild type) expression levels in PBMCs, in particular CD14+
monocytes, from SSc patients were higher than that from healthy controls.
Additionally, the overexpression experiments showed that survivin-WT
overexpressing CD1a+ Mo-DCs have the characteristics of promoting cell cycle
progression and decreasing apoptotic cells. CONCLUSIONS: These findings suggest
that dermal survivin+ CD1a+ cell infiltration may be a potential biomarker of SSc
skin lesions. PBMCs and monocytes from SSc patients also overexpressed survivin;
therefore, dermal survivin+ DC may be derived from peripheral blood monocytes.
Additionally, survivin may be involved in dermal CD1a+ DC proliferation through
cell cycle activation and resistance to apoptosis. Survivin may be an important
molecule for the pathogenesis of SSc.
PMID- 26419628
TI - Intraspecific lineage divergence and its association with reproductive trait
change during species range expansion in central Eurasian wild wheat Aegilops
tauschii Coss. (Poaceae).
AB - BACKGROUND: How species ranges form in landscapes is a matter of long-standing
evolutionary interest. However, little is known about how natural phenotypic
variations of ecologically important traits contribute to species range
expansion. In this study, we examined the phylogeographic patterns of phenotypic
changes in life history (seed production) and phenological (flowering time)
traits during the range expansion of Aegilops tauschii Coss. from the
Transcaucasus and Middle East to central Asia. RESULTS: Our comparative analyses
of the patterns of natural variations for those traits and their association with
the intraspecific lineage structure showed that (1) the eastward expansion to
Asia was driven by an intraspecific sublineage (named TauL1b), (2) high seed
production ability likely had an important role at the initial dispersal stage of
TauL1b's expansion to Asia, and (3) the phenological change to early flowering
phenotypes was one of the key adaptation events for TauL1b to further expand its
range in Asia. CONCLUSIONS: This study provides for the first time a broad
picture of the process of Ae. tauschii's eastward range expansion in which life
history and phenological traits may have had respective roles in its dispersal
and adaptation in Asia. The clear association of seed production and flowering
time patterns with the intraspecific lineage divergence found in this study
invites further genetic research to bring the mechanistic understanding of the
changes in these key functional traits during range expansion within reach.
PMID- 26419627
TI - Rare presentation of four primary pediatric cardiac tumors.
AB - Pediatric cardiac tumors are extremely rare and usually benign. We selected four
unique cases of pediatric cardiac tumors from a 15-year period at our
institution. The four chosen cases represent unique, rare primary tumors of the
heart. Our selection includes a case of Rosai Dorfman disease without systemic
involvement, which is, to our knowledge, the second case of isolated cardiac
Rosai Dorfman disease in a child. We present a case of subtotal replacement of
myocardium by granulocytic sarcoma with minimal bone marrow involvement,
representing the first reported case in a child manifested as hypertrophic
cardiomyopathy, as well as a case of a primary synovial sarcoma arising from the
atrioventricular (AV) node, representing the fourth reported pediatric case of a
cardiac synovial sarcoma, and it is the first to arise from the AV node. Finally,
we present a primary congenital infantile fibrosarcoma of the heart, which is, to
our knowledge, the first confirmed cardiac congenital infantile fibrosarcoma.
These four cases represent the need for continued inclusion of rare cardiac
conditions in a clinician's differential diagnosis. Furthermore, they present the
need for more in-depth molecular and genomic analysis of pediatric cardiac tumors
in order to identify their etiopathogenesis.
PMID- 26419630
TI - Insights into the regulation of bacteriophage endolysin: multiple means to the
same end.
AB - Antibiotics are the molecules of choice to treat bacterial infections. However,
because of the rapid emergence of drug-resistant bacteria, alternative modes of
combating infections are being envisaged. Bacteriophages, which infect and lyse
bacterial cells, may function as effective antimicrobial agents. Most
bacteriophages produce their own peptidoglycan hydrolase called endolysin or
lysin, which breaks down the cell wall of bacteria and aids in the release of
newly assembled virions. Here, we discuss several findings that help us in
understanding how endolysins are regulated. We observe that there is no common
mechanism that is followed in all cases. Many different modes of activity
regulation have been observed in endolysins, including regulation of protein
expression, translocation across the cell membrane and post-translational
modifications. These processes not only demonstrate how endolysins are made
dependent on other accessory proteins and non-protein factors for their
synthesis, translocation across the cytoplasmic membrane and activity, but also
show how autoregulation helps in maintaining the enzyme in an inactive form.
Various regulatory mechanisms that are discussed are particularly applicable to
endolysins. Nevertheless, a detailed study of these methods opens new avenues of
investigation in the area of protein translocation systems and the novel ways of
enzyme activation and regulation in bacteria.
PMID- 26419629
TI - Sunlight inhibits growth and induces markers of programmed cell death in
Plasmodium falciparum in vitro.
AB - BACKGROUND: Plasmodium falciparum is responsible for the majority of global
malaria deaths. During the pathogenic blood stages of infection, a rapid increase
in parasitaemia threatens the survival of the host before transmission of slow
maturing sexual parasites to the mosquito vector to continue the life cycle.
Programmed cell death (PCD) may provide the parasite with the means to control
its burden on the host and thereby ensure its own survival. Various environmental
stress factors encountered during malaria may induce PCD in P. falciparum. This
study is the first to characterize parasite cell death in response to natural
sunlight. METHODS: The 3D7 strain of P. falciparum was cultured in vitro in donor
erythrocytes. Synchronized and mixed-stage parasitized cultures were exposed to
sunlight for 1 h and compared to cultures maintained in the dark, 24 h later.
Mixed-stage parasites were also subjected to a second one-hour exposure at 24 h
and assessed at 48 h. Parasitaemia was measured daily by flow cytometry.
Biochemical markers of cell death were assessed, including DNA fragmentation,
mitochondrial membrane polarization and phosphatidylserine externalization.
RESULTS: Sunlight inhibited P. falciparum growth in vitro. Late-stage parasites
were more severely affected than early stages. However, some late-stage parasites
survived exposure to sunlight to form new rings 24 h later, as would be expected
during PCD whereby only a portion of the population dies. DNA fragmentation was
observed at 24 and 48 h and preceded mitochondrial hyperpolarization in mixed
stage parasites at 48 h. Mitochondrial hyperpolarization likely resulted from
increased oxidative stress. Although data suggested increased phosphatidylserine
externalization in mixed-stage parasites, results were not statistically
significant. CONCLUSION: The combination of biochemical markers and the survival
of some parasites, despite exposure to a lethal stimulus, support the occurrence
of PCD in P. falciparum.
PMID- 26419631
TI - Electro-acupuncture decreases 5-HT, CGRP and increases NPY in the brain-gut axis
in two rat models of Diarrhea-predominant irritable bowel syndrome(D-IBS).
AB - BACKGROUND: To examine whether electro-acupuncture (EA) could decrease 5
hydroxytryptamine (5-HT) and calcitonin gene-related peptide (CGRP), and increase
neuro-peptide Y (NPY) in the brain-gut axis (BGA) in D-IBS using rat models.
METHODS: Rats were randomly exposed to unpredictable chronic stress for 3 weeks
followed by 1-hour acute restraint stress (CAS) after 7 days of rest, or daily
gavage of Senna decoction (6 g/kg) plus chronic restraint stress (for a duration
of 2 h, starting from 1 h prior to the gavage) for 2 weeks (ISC). The content of
5-HT, CGRP and NPY in the distal colon, spinal cord, hypothalamus was examined at
the end of the treatment. RESULTS: 1. The two rat models exhibited similar
characteristics, e.g., increased number of fecal pellets expelled in 1 h,
decreased sacchar-intake, decreased CRD, elevated 5-HT, CGRP content and
decreased NPY in the distal colon, spinal cord, hypothalamus (P < 0.05 vs. that
in healthy control rats). 2. A series of equations was developed based on
correlation regression analysis. The analysis results demonstrated that 5-HT
mediates the changes in hypothalamus, spinal cord and colon. 5-HT and CGRP in
spinal cord was closely correlated with general behavior evaluation and other
transmitters in BGA. CONCLUSION: 1. In comparison to 5-HT, CGRP and NPY
(particularly in the spinal cord) had closer relationship with the D-IBS symptoms
induced by either stress factors or Senna decotion. 2. EA treatment could restore
the brain-gut axis to balanced levels.
PMID- 26419633
TI - A Highly Sensitive Fluorescent Sensor for Palladium and Direct Imaging of Its
Ecotoxicity in Living Model Organisms.
AB - Rhodamine is an ideal platform for fluorescence probes owing to its spiro-lactam
framework and excellent photochemical properties. Herein, a novel rhodamine-based
palladium fluorescent chemosensor, Rd-Eb, showing a fast response time (3 min),
high sensitivity for palladium species over other ions, and a low detection limit
(1.91*10(-7) m), was synthesized. It can act as an obvious colorimetric as well
as a fluorescent "off/on" sensor for Pd(2+) . In addition, it is also an
excellent sensor for in vivo imaging of Pd(2+) in zebra fish and Daphnia magna,
illuminating the impact of palladium on organisms at different growth stages with
respect to biological toxicology.
PMID- 26419632
TI - Prenatal drug exposures sensitize noradrenergic circuits to subsequent disruption
by chlorpyrifos.
AB - We examined whether nicotine or dexamethasone, common prenatal drug exposures,
sensitize the developing brain to chlorpyrifos. We gave nicotine to pregnant rats
throughout gestation at a dose (3mg/kg/day) producing plasma levels typical of
smokers; offspring were then given chlorpyrifos on postnatal days 1-4, at a dose
(1mg/kg) that produces minimally-detectable inhibition of brain cholinesterase
activity. In a parallel study, we administered dexamethasone to pregnant rats on
gestational days 17-19 at a standard therapeutic dose (0.2mg/kg) used in the
management of preterm labor, followed by postnatal chlorpyrifos. We evaluated
cerebellar noradrenergic projections, a known target for each agent, and
contrasted the effects with those in the cerebral cortex. Either drug augmented
the effect of chlorpyrifos, evidenced by deficits in cerebellar beta-adrenergic
receptors; the receptor effects were not due to increased systemic toxicity or
cholinesterase inhibition, nor to altered chlorpyrifos pharmacokinetics. Further,
the deficits were not secondary adaptations to presynaptic
hyperinnervation/hyperactivity, as there were significant deficits in presynaptic
norepinephrine levels that would serve to augment the functional consequence of
receptor deficits. The pretreatments also altered development of cerebrocortical
noradrenergic circuits, but with a different overall pattern, reflecting the
dissimilar developmental stages of the regions at the time of exposure. However,
in each case the net effects represented a change in the developmental trajectory
of noradrenergic circuits, rather than simply a continuation of an initial
injury. Our results point to the ability of prenatal drug exposure to create a
subpopulation with heightened vulnerability to environmental neurotoxicants.
PMID- 26419634
TI - Alcohol Use Disorder and Heavy Episodic Drinking in Rural Communities in
Cambodia: Risk Factors and Community-Perceived Strategies.
AB - Alcohol misuse is increasing in Southeast Asia. We investigated the extent of and
risk factors for alcohol use disorder (AUD) and heavy episodic drinking (HED) in
a rural community in Cambodia. We also attempted to explore the communities'
perception of alcohol misuse and elicited potential community-based strategies to
address the alcohol problem. A mixed-methods study design was used, combining a
cross-sectional questionnaire survey with qualitative interviews (focus group
discussions and key informant interviews). AUD and HED were measured using the
AUDs Identification Test Alcohol Consumption questionnaire. The prevalence of AUD
and HED was high: 25% and 31%, respectively. Male sex, younger age, and
increasing income were significant risk factors. The communities were well aware
of the harmful effects of alcohol, expressed the importance of implementing
community-based measures, and proposed various community-led solutions. Evidence
based strategies that are culturally appropriate, accepted, and driven by
communities are urgently needed.
PMID- 26419635
TI - Health Literacy in Taiwan: A Population-Based Study.
AB - Data on health literacy (HL) in the population is limited for Asian countries.
This study aimed to test the validity of the Mandarin version of the European
Health Literacy Survey Questionnaire (HLS-EU-Q) for use in the general public in
Taiwan. Multistage stratification random sampling resulted in a sample of 2989
people aged 15 years and above. The HLS-EU-Q was validated by confirmatory factor
analysis with excellent model data fit indices. The general HL of the Taiwanese
population was 34.4 +/- 6.6 on a scale of 50. Multivariate regression analysis
showed that higher general HL is significantly associated with the higher ability
to pay for medication, higher self-perceived social status, higher frequency of
watching health-related TV, and community involvement but associated with younger
age. HL is also associated with health status, health behaviors, and health care
accessibility and use. The HLS-EU-Q was found to be a useful tool to assess HL
and its associated factors in the general population.
PMID- 26419636
TI - Validation of WHOQOL-BREF in Malayalam and Determinants of Quality of Life Among
People With Type 2 Diabetes in Kerala, India.
AB - Quality of life (QOL) is an important health outcome in people with chronic
conditions like diabetes and WHOQOL-BREF is a popular instrument used worldwide
to assess QOL. However, QOL varies considerably from society to society depending
on the culture of the person. Hence, the WHOQOL-BREF was translated to the local
language, Malayalam. This article attempts to establish reliability, construct
and discriminant validity of the translated WHOQOL-BREF, and determinants of QOL
among people with type 2 diabetes. A cross-sectional study was undertaken among
200 patients with diabetes attending a primary care center in a rural area of
Kerala, India. The translated version of WHOQOL-BREF was found to be internally
consistent (Cronbach's alpha = .86) and demonstrated discriminant and construct
validity. Education was found to be an independent determinant of QOL in the
physical, psychological, and environmental domains. Thus, the translated version
had good psychometric properties and education was an independent determinant of
QOL in 3 of 4 domains.
PMID- 26419637
TI - New synthesis of phenyl-isothiocyanate C-functionalised cyclams. Bioconjugation
and (64)Cu phenotypic PET imaging studies of multiple myeloma with the te2a
derivative.
AB - Azamacrocyclic bifunctional chelating agents (BCAs) are essential for the
development of radiopharmaceuticals in nuclear medicine and we wish to prove that
their bioconjugation by a function present on a carbon atom of the macrocyclic
skeleton is a solution of choice to maintain their in vivo inertness. Based on
our very recent methodology using a bisaminal template and selective N-alkylation
approach, a new synthesis of conjugable C-functionalised teta, te2a and cb-te2a
has been developed. These chelators have indeed a growing interest in nuclear
medicine for positron emission tomography (PET) and radioimmunotherapy (RIT)
where they show in several cases better complexation properties than dota or dota
like macrocycles, especially with (64)Cu or (67)Cu radioisotopes. Chelators are
bearing an isothiocyanate grafting function introduced by C-alkylation to avoid
as much as possible a critical decrease of their chelating properties. The
synthesis is very efficient and yields the targeted ligands, teta-Ph-NCS, te2a-Ph
NCS and cb-te2a-Ph-NCS without fastidious work-up and could be easily extended to
other cyclam based-BCAs. The newly synthetised te2a-Ph-NCS has been conjugated to
an anti mCD138 monoclonal antibody (mAb) to evaluate its in vivo behavior and
potentiality as BCA and to explore a first attempt of PET-phenotypic imaging in
multiple myeloma (MM). Mass spectrometry analysis of the immunoconjugate showed
that up to 4 chelates were conjugated per 9E7.4 mAb. The radiolabeling yield and
specific activity post-purification of the bioconjugate 9E7.4-CSN-Ph-te2a were 95
+/- 2.8% and 188 +/- 27 MBq mg(-1) respectively and the immunoreactivity of
(64)Cu-9E7.4-CSN-Ph-te2a was 81 +/- 7%. Animal experiments were carried out on
5T33-Luc(+) tumor bearing mice, either in subcutaneous or orthotopic. To achieve
PET imaging, mice were injected with (64)Cu-9E7.4-CNS-Ph-te2a and acquisitions
were conducted 2 and 20 h post-injection (PI). A millimetric bone uptake was
localised in a sacroiliac of a MM orthotopic tumor. Nonspecific uptakes were
observed at 2 h PI but, unlike for the tumor, a significant decrease was observed
at 20 h PI which improves the contrast of the images.
PMID- 26419642
TI - A Comprehensive Assessment Tool for Patient Registry Software Systems: The CIPROS
Checklist.
AB - BACKGROUND: Patient registries are an important instrument in medical research.
Often their structure is complex and their implementation uses composite software
systems to meet the wide spectrum of challenges. OBJECTIVES: For the
implementation of a registry, there is a wide range of commercial, open source,
and self-developed systems available and a minimal standard for the critical
appraisal of their architecture is needed. METHODS: We performed a systematic
review of the literature to define a catalogue of relevant criteria to construct
a minimal appraisal standard. RESULTS: The CIPROS list is developed based on 64
papers which were found by our systematic review. The list covers twelve sections
and contains 72 items. CONCLUSIONS: The CIPROS list supports developers to assess
requirements on existing systems and strengthens the reporting of patient
registry software system descriptions. It can be a first step to create standards
for patient registry software system assessments.
PMID- 26419644
TI - Effect of intra-abdominal administration of ligustrazine nanoparticles nano spray
on postoperative peritoneal adhesion in rat model.
AB - AIM: We aimed to evaluate the preventive effect of the ligustrazine nanoparticles
nano spray (LNNS) for postoperative peritoneal adhesions in female rat models.
MATERIAL AND METHODS: Fifty Wistar female rats weighting 250-300 g were randomly
assigned to seven equal groups. All animals in the seven groups underwent midline
laparotomy and ceca were abraded with sterile rasp. Group 1 underwent sham
operations without treatment. In group 2, a postoperative peritoneal adhesion
model was created, but no medication was given. In group 3, a postoperative
peritoneal adhesion model was treated with LNNS, 2.5 mg/kg. In group 4, a
postoperative peritoneal adhesion model was treated with LNNS, 5 mg/kg. In group
5, a postoperative peritoneal adhesion model was treated with LNNS, 10 mg/kg. In
group 6, a postoperative peritoneal adhesion model was treated with polylactic
acid (PLA) nanoparticle. In group 7, a postoperative peritoneal adhesion model
was treated with ligustrazine, 2.5 mg/kg. Ten days after surgery, macroscopic and
pathologic assessments were performed, and peritoneal fluid samples were
collected in each group. The levels of tumor necrosis factor-alpha, tissue
plasminogen activator and plasminogen activator inhibitor-1 in peritoneal fluid
were determined by enzyme-linked immunosorbent assay. RESULTS: The adhesion score
and extent of groups 4 and 5 was lower than that of group 2 in macroscopic
assessment (P < 0.05). A comparison of tumor necrosis factor-alpha and tissue
plasminogen activator level in the peritoneal fluid also demonstrated significant
differences among groups 2, 4 and 5 (P < 0.05). The levels of plasminogen
activator inhibitor-1 in peritoneal fluid in the LNNS groups were decreased
compared to group 1. CONCLUSION: We suggest that LNNS could reduce peritoneal
adhesion formation and it could be applied as a novel intervention for
postoperative peritoneal adhesion.
PMID- 26419646
TI - W-DARE: a three-year program of participatory action research to improve the
sexual and reproductive health of women with disabilities in the Philippines.
AB - BACKGROUND: In many contexts, women with disability have less access to sexual
and reproductive health information, screening, prevention, and care services
than women without disability. Women with disability are also known to be more
likely to experience physical and sexual violence than women without disability.
In the Philippines, health service providers often have little awareness of the
sexual and reproductive experiences of women with disability and limited capacity
to provide services in response to their needs. Very limited data are available
to inform development of disability-inclusive sexual and reproductive health, and
violence prevention and response, services in the country. This paper presents
the protocol for W-DARE (Women with Disability taking Action on REproductive and
sexual health), a three-year program of participatory action research that aims
to improve the sexual and reproductive health of women with disability in the
Philippines. DESIGN: W-DARE is a disability-inclusive program that will use mixed
methods to 1) increase understanding of factors influencing the sexual and
reproductive health of women with disability, and 2) develop, implement and
evaluate local interventions to increase supply of and demand for services. W
DARE will generate data on the prevalence of disability in two districts; the
wellbeing and community participation of people with and without disability, and
identify barriers to community; and describe the sexual and reproductive health
needs and experiences, and service-related experiences of women with disability.
These data will inform the development and evaluation of interventions aiming to
improve access to sexual and reproductive health services, and violence
prevention and response services, for women with disability. Local women with
disabilities, their representative organisations, and SRH service providers will
be involved as members of the research team across all stages of the research.
DISCUSSION: This three-year study will provide evidence about factors undermining
the sexual and reproductive health of women with disability in a lower-middle
income country, and provide new insights about what may be effective in
increasing access to services in settings of limited resources. Findings will be
relevant across Asia and the Pacific. Analysis of the program will also provide
evidence about disability-inclusion in participatory action research approaches.
PMID- 26419645
TI - VMAT-SBRT planning based on an average intensity projection for lung tumors
located in close proximity to the diaphragm: a phantom and clinical validity
study.
AB - The aim of the this study was to validate the use of an average intensity
projection (AIP) for volumetric-modulated arc therapy for stereotactic body
radiation therapy (VMAT-SBRT) planning for a moving lung tumor located near the
diaphragm. VMAT-SBRT plans were created using AIPs reconstructed from 10 phases
of 4DCT images that were acquired with a target phantom moving with amplitudes of
5, 10, 20 and 30 mm. To generate a 4D dose distribution, the static dose for each
phase was recalculated and the doses were accumulated by using the phantom
position known for each phase. For 10 patients with lung tumors, a deformable
registration was used to generate 4D dose distributions. Doses to the target
volume obtained from the AIP plan and the 4D plan were compared, as were the
doses obtained from each plan to the organs at risk (OARs). In both phantom and
clinical study, dose discrepancies for all parameters of the dose volume (D(min),
D(99), D(max), D(1) and D(mean)) to the target were <3%. The discrepancies of
D(max) for spinal cord, esophagus and heart were <1 Gy, and the discrepancy of
V20 for lung tissue was <1%. However, for OARs with large respiratory motion, the
discrepancy of the D(max) was as much as 9.6 Gy for liver and 5.7 Gy for stomach.
Thus, AIP is clinically acceptable as a planning CT image for predicting 4D dose,
but doses to the OARs with large respiratory motion were underestimated with the
AIP approach.
PMID- 26419649
TI - Multi-slice MRI with the dynamic multi-coil technique.
AB - To date, spatial encoding for MRI is based on linear X, Y and Z field gradients
generated by dedicated X, Y and Z wire patterns. We recently introduced the
dynamic multi-coil technique (DYNAMITE) for the generation of magnetic field
shapes for biomedical MR applications from a set of individually driven localized
coils. The benefits for B0 magnetic field homogenization have been shown, as well
as proof of principle of radial and algebraic MRI. In this study the potential of
DYNAMITE MRI is explored further and the first multi-slice MRI implementation in
which all gradient fields are purely DYNAMITE based is presented. The obtained
image fidelity is shown to be virtually identical to that of a conventional MRI
system with dedicated X, Y and Z gradient coils. Comparable image quality is a
milestone towards the establishment of fully functional DYNAMITE MRI (and shim)
systems.
PMID- 26419647
TI - Transoral laser microsurgery for the treatment of oropharyngeal cancer: the
Dalhousie University experience.
AB - OBJECTIVE: The optimal treatment strategy for oropharyngeal squamous cell
carcinoma is highly debated. However, growing evidence supports the use of
minimally invasive techniques, such as transoral laser microsurgery (TLM), as a
first-line treatment modality for these carcinomas. The purpose of our study was
to assess the efficacy and safety of TLM for the treatment of primary and
recurrent oropharyngeal carcinomas. METHODS: All patients with oropharyngeal
carcinoma undergoing TLM at the QEII Health Sciences Centre in Halifax, Nova
Scotia were identified within a prospective database monitoring TLM outcomes.
Kaplan-Meier survival analysis was used to evaluate the following end points at
36 months: local control (LC), disease-specific survival (DSS), and disease-free
survival (DFS). Safety endpoints included complications following surgery and
long term morbidity related to TLM. RESULTS: Between 2003 and 2014, 39 patients
with oropharyngeal carcinoma underwent TLM resection. Twenty-eight (72%) patients
had primary carcinoma, nine (23%) were radiation/chemoradiation (RT/CRT)
failures, and two (5%) had second primaries following previous RT/CRT. Three
patients had stage I disease, 8 stage II, 5 stage III, and 23 stage IV disease.
HPV status was available for 26 patients, of which 23 (88%) had HPV positive
disease. Kaplan-Meier estimates of 36-month LC, DSS, and DFS for primary
oropharyngeal carcinomas were 85.5% (SE 10.6%), 85.7% (SE 13.2%) and 77.7% (SE
12.5%) respectively. Thirty-six-month outcomes for RT/CRT failures were 66.76%
(SE 15.7%) for LC and 55.6% (SE 16.6%) for DSS and DFS. Three patients developed
complications following surgery. CONCLUSIONS: Observed 36-month efficacy and
safety outcomes support the use of TLM for the treatment of primary and recurrent
oropharyngeal carcinoma.
PMID- 26419650
TI - Randomised control trial of humidified high flow nasal cannulae versus standard
oxygen in the emergency department.
AB - OBJECTIVES: The aim of the study was to determine if oxygen delivered through
humidified high flow nasal cannulae (HHFNC) reduced the need for escalation in
ventilation management and work of breathing in the ED patients presenting with
acute undifferentiated shortness of breath compared with standard oxygen therapy.
METHODS: This was an unblinded randomised control trial conducted at two hospital
EDs in Sydney, Australia. Eligible patients presenting with shortness of breath
were randomised to HHFNC or standard oxygen therapy. Primary outcomes were the
need to escalate ventilation therapy or a reduction in respiratory rate of 20% or
more within 2 h of commencement. RESULTS: One hundred patients were enrolled in
the trial. The intervention group receiving HHFNC was associated with a higher
proportion of patients with a reduced respiratory rate at 2 h (66.7% vs 38.5%, P
= 0.005) and a lower proportion of patients requiring escalation in ventilation
therapy (4.2% vs 19%, P = 0.02) compared with standard oxygen therapy.
CONCLUSIONS: The use of high flow nasal cannula oxygenation was associated with
improved respiratory state in selected patients presenting to the ED with acute
undifferentiated shortness of breath.
PMID- 26419643
TI - Developmental regulation of fear learning and anxiety behavior by
endocannabinoids.
AB - The developing brain undergoes substantial maturation into adulthood and the
development of specific neural structures occurs on differing timelines.
Transient imbalances between developmental trajectories of corticolimbic
structures, which are known to contribute to regulation over fear learning and
anxiety, can leave an individual susceptible to mental illness, particularly
anxiety disorders. There is a substantial body of literature indicating that the
endocannabinoid (eCB) system critically regulates stress responsivity and
emotional behavior throughout the life span, making this system a novel
therapeutic target for stress- and anxiety-related disorders. During early life
and adolescence, corticolimbic eCB signaling changes dynamically and coincides
with different sensitive periods of fear learning, suggesting that eCB signaling
underlies age-specific fear learning responses. Moreover, perturbations to these
normative fluctuations in corticolimbic eCB signaling, such as stress or
cannabinoid exposure, could serve as a neural substrate contributing to
alterations to the normative developmental trajectory of neural structures
governing emotional behavior and fear learning. In this review, we first
introduce the components of the eCB system and discuss clinical and rodent models
showing eCB regulation of fear learning and anxiety in adulthood. Next, we
highlight distinct fear learning and regulation profiles throughout development
and discuss the ontogeny of the eCB system in the central nervous system, and
models of pharmacological augmentation of eCB signaling during development in the
context of fear learning and anxiety.
PMID- 26419648
TI - Usual blood pressure, peripheral arterial disease, and vascular risk: cohort
study of 4.2 million adults.
AB - OBJECTIVES: To determine the subgroup specific associations between usual blood
pressure and risk of peripheral arterial disease, and to examine the relation
between peripheral arterial disease and a range of other types of vascular
disease in a large contemporary cohort. DESIGN: Cohort study. SETTING: Linked
electronic health records from 1990 to 2013 in the United Kingdom. PARTICIPANTS:
4,222,459 people aged 30-90 years, registered at a primary care practice for at
least one year and with a blood pressure measurement. MAIN OUTCOME MEASURES: Time
to first diagnosis of new onset peripheral arterial disease and time to first
diagnosis of 12 different vascular events. RESULTS: A 20 mm Hg higher than usual
systolic blood pressure was associated with a 63% higher risk of peripheral
arterial disease (hazard ratio 1.63, 95% confidence interval 1.59 to 1.66). The
strength of the association declined with increasing age and body mass index
(P<0.001 for interaction) but was not modified by sex or smoking status.
Peripheral arterial disease was associated with an increased risk of 11 different
vascular events, including ischaemic heart disease (1.68, 1.58 to 1.79), heart
failure (1.63, 1.52 to 1.75), aortic aneurysm (2.10, 1.79 to 2.45), and chronic
kidney disease (1.31, 1.25 to 1.38), but not haemorrhagic stroke. The most common
initial vascular event among those with peripheral arterial disease was chronic
kidney disease (24.4% of initial events), followed by ischaemic heart disease
(18.5% of initial events), heart failure (14.7%), and atrial fibrillation
(13.2%). Overall estimates from this cohort were consistent with those derived
from traditional studies when we pooled the findings in two meta-analyses.
CONCLUSIONS: Raised blood pressure is a strong risk factor for peripheral
arterial disease in a range of patient subgroups. Furthermore, clinicians should
be aware that those with established peripheral arterial disease are at an
increased risk of a range of other vascular events, including chronic kidney
disease, ischaemic heart disease, heart failure, atrial fibrillation, and stroke.
PMID- 26419651
TI - Emergent roles for intercellular adhesion molecule-1 in the restructuring of the
blood-testis barrier during spermatogenesis in the mammal.
AB - Mammalian spermatogenesis is comprised of a series of molecular, cellular, and
morphological events that underscore the movement of developing germ cells across
the blood-testis barrier. These events involve the restructuring of tight
junctions, basal ectoplasmic specializations, gap junctions, and desmosomes,
which constitute blood-testis barrier function. Previous studies show that
preleptotene/leptotene spermatocytes traverse the blood-testis barrier while
transiently trapped within an intermediate compartment, which sequesters primary
spermatocytes away from basal and adluminal compartments of the seminiferous
epithelium. Preleptotene/leptotene spermatocytes enter the adluminal compartment
when stable junctions ahead of spermatocytes disassemble, while new junctions
assemble behind them. While there is enormous restructuring of the seminiferous
epithelium, the mechanism of germ cell movement is incompletely understood. In
this perspective, the significance of intercellular adhesion molecule-1 in the
restructuring of the blood-testis barrier during spermatogenesis in the mammal is
discussed.
PMID- 26419653
TI - Foodborne illness among factory workers, Gweru, Zimbabwe, 2012: a retrospective
cohort study.
AB - BACKGROUND: On the 20th September 2012 the Gweru district medical officer (DMO)
reported a sudden increase in the number of factory workers complaining of
symptoms suggestive of gastrointestinal illness. We conducted a retrospective
cohort study to determine factors associated with illness among factory workers.
METHODS: A retrospective cohort study was conducted from September to October
2012 among 98 randomly selected factory workers. Interviewer administered
questionnaires were used to evaluate possible risk factors from which food attack
rates, relative risks (RR) and adjusted odds ratios (AOR) were calculated using
Epi info version 3.5.1. Bacteriological examination of food samples was
performed. In addition rectal swabs and specimens from food handlers and patients
were collected for analysis. RESULTS: Of the 98 workers interviewed, 87/98 (89%)
were males. Consumption of beef stew (AOR = 9.28, 95% CI 2.78-30.91) was
independently associated with foodborne illness. Klebsiella spp. were isolated
from beef stew and stool specimen of patients. Watery diarrhoea 51/98 (52%),
fatigue 48/98 (49%) and abdominal cramps 41/98 (42%) were the most presenting
symptoms. CONCLUSIONS: Klebsiella spp. was the aetiological agent for the food
borne illness at the factory and this resulted from consumption of contaminated
beef stew by the workers. As a result of this evidence, the implicated beef was
withdrawn from the canteen and the menu cycle was revised to minimise exposure to
the same food. Food handlers training in food safety and hygiene and regular
canteen inspections for quality assurance were recommended and adopted. No
further food borne illness has been reported from the factory.
PMID- 26419652
TI - A retrospective analysis of ethnic and gender differences in alcohol consumption
among emergency department patients: a cross-sectional study.
AB - BACKGROUND: Previous studies of alcohol use have recognized several trends in
consumption patterns among gender and age yet few have examined ethnic
differences. This study examines the intra- and inter-ethnic differences in
alcohol consumption among a population of patients seen in the emergency
department. METHODS: This is a cross-sectional study conducted in the emergency
department in a large urban setting. Information on drinking behavior and
ethnicity was collected using the Computerized Alcohol Screening and Brief
Intervention (CASI) tool. We explored differences in drinking patterns using a
multivariate multinomial logistic regression model. RESULTS: We analyzed the
drinking habits of 2,444 patients surveyed between November 2012 and May 2014.
The results indicate that when compared to non-Hispanic whites, Asians have the
lowest odds of drinking within normal limits or excessively, followed by other
Latinos, and Mexicans. Age and gender consistently showed statistically
significant associations with alcohol-use. The odds of drinking within normal
limits or excessively are inversely associated with age and were lower among
females. The predicted probabilities show a marked gender-specific difference in
alcohol use both between and within ethnic/racial groups. They also highlight an
age-related convergence in alcohol use between men and women within ethnic
groups. DISCUSSION: The results of this study show intra-racial/ethnic
variability associated with sex and education. The highlighted differences within
and between ethnic groups reinforce the need to use refined categories when
examining alcohol use among minorities. CONCLUSION: The results of this study
confirm some alcohol consumption trends among ethnic minorities observed in
literature. It provides empirical evidence of the marked gender differences and
highlights an age-related convergence for gender-specific alcohol use. Health
care personnel should be aware of these differences when screening and
counseling.
PMID- 26419654
TI - All-cause mortality effects of replacing sedentary time with physical activity
and sleeping using an isotemporal substitution model: a prospective study of
201,129 mid-aged and older adults.
AB - BACKGROUND: Sedentary behaviour, sleeping, and physical activity are thought to
be independently associated with health outcomes but it is unclear whether these
associations are due to the direct physiological effects of each behaviour or
because, across a finite 24-hour day, engagement in one behavior requires
displacement of another. The aim of this study was to examine the replacement
effects of sedentary behaviour (total sitting, television/computer screen time
combined), sleeping, standing, walking, and moderate-to-vigorous physical
activity on all-cause mortality using isotemporal substitution modelling.
METHODS: Longitudinal analysis (4.22 +/- 0.9 years follow-up/849,369 person
years) of 201,129 participants of the 45 and Up study aged >=45 years from New
South Wales, Australia. RESULTS: Seven thousand four hundred and sixty deaths
occurred over follow-up. There were beneficial associations for replacing total
sitting time with standing (per-hour HR: 95 % CI: 0.95, 0.94-0.96), walking
(0.86, 0.81-0.90), moderate-to-vigorous physical activity (0.88, 0.85-0.90), and
sleeping in those sleeping <= 7 h/day (0.94, 0.90-0.98). Similar associations
were noted for replacing screen time. Replacing one hour of walking or moderate
to-vigorous physical activity with any other activity class was associated with
an increased mortality risk by 7-18%. Excluding deaths in the first 24 months of
the follow up and restricting analyses to those who were healthy at baseline did
not materially change the above observations. CONCLUSION: Although replacing
sedentary behaviour with walking and moderate-to-vigorous physical activity are
associated with the lowest mortality risk, replacements with equal amounts of
standing and sleeping (in low sleepers only) are also linked to substantial
mortality risk reductions.
PMID- 26419655
TI - Time trends and epidemiological patterns of perinatal lamb mortality in Norway.
AB - BACKGROUND: Perinatal mortality is a major cause of loss in the sheep industry.
Our aim was to explore time trends in crude population stillbirth and neonatal
mortality rates in Norway. We used data on 6,435,715 lambs from flocks enrolled
in the Norwegian Sheep Recording System (NSRS) from 2000 through 2010 for
descriptive analysis of trends. Longitudinal patterns of mortality rates were
compared for lambs within different levels of variables suspected to be
associated with perinatal loss. RESULTS: There was an approximately linear
increase in the annual proportion of stillborn lambs during the study period,
from 3.3 % in 2000 to 4.7 % in 2010. In the same time period, average litter size
of ewes in NSRS flocks increased from 2.00 to 2.19. However, a steady rise in
stillbirth rate was observed within each litter size group, suggesting a
gradually increasing impact on stillbirth risk of other, yet unidentified,
factors. Average flock size increased during the study period. The highest
stillbirth rates were found in the largest and smallest flocks. Early neonatal
mortality rates (0-5 days of life) varied from year to year (minimum 2.2 %,
maximum 3.2 %) and were invariably higher among triplets and quadruplets than
among singletons and twins. Annual fluctuations were parallel within the various
litter sizes. A significant overall decreasing trend was present within all
litter sizes with the exception of singletons. Weather data for the prime lambing
months (April and May) 2000-2010 indicated a relationship between low
temperatures and high neonatal mortality rates. At the flock level, there was a
significant positive correlation between stillbirths and early neonatal mortality
rates (r = 0.13), between stillbirth rates in two consecutive years (r = 0.43)
and between early neonatal mortality rates in two consecutive years (r = 0.40).
CONCLUSIONS: The substantial increase in ovine stillbirth rate in recent years in
Norway was to some extent related to a corresponding increase in the proportion
of lambs in triplet or larger litters; however, other factors apparently have
contributed. Early neonatal mortality rate exhibited year-to-year variations,
partly following temperature fluctuations, which is somewhat unexpected,
considering that lambing mainly occurs indoors in Norway.
PMID- 26419656
TI - Homo and heteropolymetallic Group 4 molecular nitrides.
AB - Treatment of [{Ti(eta(5)-C5Me5)(MU-NH)}3(MU3-N)] (1) with zirconium or hafnium
tetrachloride adducts [MCl4(thf)2] affords complexes [Cl3M{(MU3-N)(MU3
NH)2Ti3(eta(5)-C5Me5)3(MU3-N)}] (M = Zr (2), Hf (3)). Titanium chloride complexes
[Cl2Ti{(MU3-N)2(MU3-NH)Ti3(eta(5)-C5Me5)3(MU3-N)}] (4) and [(Me2NH)ClTi{(MU3
N)3Ti3(eta(5)-C5Me5)3(MU3-N)}] (5) are obtained by reaction of 1 with [TiCl4
x(NMe2)x] (x = 2, 3). The dimethylamine ligand in 5 is displaced by pyridine to
give the analogue complex [(py)2ClTi{(MU3-N)3Ti3(eta(5)-C5Me5)3(MU3-N)}] (6).
Treatment of the titanium chloride complexes 4 and 5 with sodium
cyclopentadienide or lithium bis(trimethylsilyl)amide reagents leads to the cube
type nitrido derivatives [RTi{(MU3-N)3Ti3(eta(5)-C5Me5)3(MU3-N)}] (R = eta(5)
C5H5 (7), N(SiMe3)2 (8)). The reaction of the zirconium trichloride complex 2
with [Tl(C5H5)] yields exclusively the dichloride-monocyclopentadienyl derivative
[(eta(5)-C5H5)Cl2Zr{(MU3-N)(MU3-NH)2Ti3(eta(5)-C5Me5)3(MU3-N)}] (9). However, the
treatment of 2 with excess [Na(C5H5)] causes further chloride replacement in 9
and subsequent cyclopentadiene elimination to give [(eta(5)-C5H5)Zr{(MU3
N)3Ti3(eta(5)-C5Me5)3(MU3-N)}] (10) via intermediates [(eta(5)-C5H5)2ClZr{(MU3
N)Ti3(eta(5)-C5Me5)3(MU-NH)2(MU3-N)}] (11) and [(eta(5)-C5H5)ClZr{(MU3-N)2(MU3
NH)Ti3(eta(5)-C5Me5)3(MU3-N)}] (12). Treatment of 2 or 9 with [Mg(C5H5)2] leads
to the magnesium derivative [(eta(5)-C5H5)Mg(MU-Cl)2(eta(5)-C5H5)Zr{(MU4-N)(MU3
N)(MU3-NH)Ti3(eta(5)-C5Me5)3(MU3-N)}] (13), which can be visualized as a result
of the incorporation of one [Mg(eta(5)-C5H5)Cl] moiety to complex 12. In contrast
to the metathesis process with [M(C5H5)x] derivatives and subsequent C5H6
eliminations, the reaction of 2 with potassium pentamethylcyclopentadienide in
toluene produces the paramagnetic derivative [K(MU-Cl)3Zr{(MU3-N)(MU3
NH)2Ti3(eta(5)-C5Me5)3(MU3-N)}] (14) and C10Me10. Complex 14 reacts with one
equivalent of 18-crown-6 or cryptand-222 to give the molecular complex [(18-crown
6)K(MU-Cl)3Zr{(MU3-N)(MU3-NH)2Ti3(eta(5)-C5Me5)3(MU3-N)}] (15) or the ion pair
[K(crypt-222)][Cl3Zr{(MU3-N)(MU3-NH)2Ti3(eta(5)-C5Me5)3(MU3-N)}] (16). The X-ray
crystal structures of 2, 8, 13 and 15 have been determined.
PMID- 26419657
TI - Prevalence and determinants of symptoms of common mental disorders in retired
professional Rugby Union players.
AB - The primary aim of this study was to determine the prevalence of symptoms of
common mental disorders (CMD) (distress, anxiety/depression, sleeping
disturbance, adverse nutrition behaviour, adverse alcohol behaviour and smoking)
among retired professional Rugby Union players. The secondary aim was to explore
the associations between stressors (life events, Rugby Union career
dissatisfaction) and the health conditions under study. Therefore, cross
sectional analyses were conducted on baseline questionnaires from an ongoing
prospective cohort study of retired professional Rugby Union players. An
electronic questionnaire was established using validated questionnaires to assess
symptoms of CMD and stressors. The electronic questionnaire was subsequently
distributed to retired players by the national Rugby Union players' associations
in France, Ireland and South Africa. Among 295 retired professional Rugby Union
players (mean age of 38 years), prevalence rates were 25% for distress, 28% for
anxiety/depression, 29% for sleeping disturbance, 62% for adverse nutrition
behaviour, 15% for smoking and 24% for adverse alcohol behaviour. A higher number
of life events were associated with distress (OR = 1.2; 95% CI 1.1-1.4),
anxiety/depression (OR = 1.6; 95% CI 1.2-2.1), sleeping disturbance (OR = 1.6;
95% CI 1.2-2.1) and adverse nutrition behaviour (OR = 1.8; 95% CI 1.3-2.5). A
higher level of dissatisfaction of the player's Rugby Union career was associated
with distress (OR = 0.9; 95% CI 0.8-1.0), sleeping disturbance (OR = 0.9; 95% CI
0.9-1.0), smoking (OR = 0.9; 95% CI 0.9-1.0) and adverse nutrition behaviour (OR
= 0.9; 95% CI 0.8-0.9). In conclusion, our study suggests that prevalence of
symptoms of CMD is high among retired professional Rugby Union players, being
associated with both a higher number of life events and a higher level of Rugby
Union career dissatisfaction.
PMID- 26419658
TI - RALA-mediated delivery of FKBPL nucleic acid therapeutics.
AB - AIMS: RALA is a novel 30 mer bioinspired amphipathic peptide that is showing
promise for gene delivery. Here, we used RALA to deliver the FK506-binding
protein like - FKBPL gene (pFKBPL) - a novel member of the immunophilin protein
family. FKBPL is a secreted protein, with overexpression shown to inhibit
angiogenesis, tumor growth and stemness, through a variety of intra- and
extracellular signaling mechanisms. We also elucidated proangiogenic activity and
stemness after utilizing RALA to deliver siRNA (siFKBPL). MATERIALS & METHODS:
The RALA/pFKBPL and RALA/siFKBPL nanoparticles were characterized in terms of
size, charge, stability and toxicity. Overexpression and knockdown of FKBPL was
assessed in vitro and in vivo. RESULTS: RALA delivered both pFKBPL and siFKBPL
with less cytotoxicity than commercially available counterparts. In vivo,
RALA/pFKBPL delivery retarded tumor growth, and prolonged survival with an
associated decrease in angiogenesis, while RALA/siFKBPL had no effect on tumor
growth rate or survival, but resulted in an increase in angiogenesis and
stemness. CONCLUSION: RALA is an effective delivery system for both FKBPL DNA and
RNAi and highlights an alternative therapeutic approach to harnessing FKBPL's
antiangiogenic and antistemness activity.
PMID- 26419659
TI - Response Surface Optimization for Decaffeination and Theophylline Production by
Fusarium solani.
AB - Coffee processing industries generate caffeine-containing waste that needs to be
treated and decaffeinated before being disposed. Five fungal isolates obtained on
caffeine-containing mineral media were tested for their ability to utilize
caffeine at high concentrations. An isolate identified as Fusarium solani could
utilize caffeine as a sole source of carbon and nitrogen up to 5 g/l and could
degrade it to an extent of 30-53 % in 120 h. Sucrose that was added as an
auxiliary substrate (5 g/l) enhanced the biodecaffeination of caffeine to 88 % in
96 h. The addition of co- substrate (sucrose) not only resulted in higher
biodecaffeination efficiency, but also reduced the incubation period from the
initial 120 to 96 h. Theophylline and 3-methyl xanthine were obtained as the
major metabolites of decaffeination at 96 and 120 h, respectively. Response
surface methodology used to optimize the process parameters for maximum
biodecaffeination as well as theophylline production showed that a pH of 5.8,
temperature of 24 degrees C and inoculum size of 4.8 * 10(5) spores/ml have
resulted in a complete biodecaffeination of caffeine as well as the production of
theophylline with a yield of 33 % (w/w). Results thus show that a viable and
sustainable process can be developed for the detoxification of caffeine along
with the recovery of theophylline, a commercially important chemical.
PMID- 26419660
TI - Isolation and Characterization of Bacteria That Use Furans as the Sole Carbon
Source.
AB - Five bacterial strains were isolated from wastewater treatment facilities which
were able to use furfural as the sole carbon source. Based on 16S rRNA
phylogenetic analysis, these strains were identified as Cupriavidus
pinatubonensis (designated ALS1280), Pigmentiphaga sp. (ALS1172), Pseudomonas sp.
BWDY (ALS1279), Pseudomonas mendocina (ALS1131), and Pseudomonas putida
(ALS1267). In all cases, growth under oxygenated conditions on furfural was
accompanied by the transient accumulation of 2-furoic acid (furoate) with no
furfuryl alcohol observed. ALS1267 and ALS1279 were also able to metabolize 5
(hydroxymethyl)furfural. The five isolates and their phylogenetic near neighbors
were compared for furfural dehydrogenase activity and tolerance to furfural and
furoate in defined and complex media. P. putida ALS1267 was the most tolerant to
furans and tolerated 17 mM furfural or 195 mM furoate before its growth rate was
reduced by 50 % in a defined medium. This strain also had the greatest specific
growth rate on furfural (0.6/h at 27-30 degrees C) and showed the highest
specific activity of furfural dehydrogenase (170 mIU/mg) of any furfural
utilizing strain that has been characterized to date.
PMID- 26419661
TI - Commentary: Vitamin D: prime mover or fellow traveller?
PMID- 26419662
TI - Vocal response inhibition is enhanced by anodal tDCS over the right prefrontal
cortex.
AB - Stopping outright (reactive inhibition) and slowing down (proactive inhibition)
are types of response inhibition which have mainly been investigated in the
manual effector system. This study compared reactive inhibition across manual and
vocal effector systems, examined the effects of excitatory anodal transcranial
direct current stimulation (anodal tDCS) over the right prefrontal cortex (right
PFC) and looked at the relationship between reactive and proactive inhibition. We
hypothesised (1) that vocal reactive inhibition would be less effective than
manual reactive inhibition as evidenced by longer stop signal reaction times; (2)
that anodal tDCS would enhance both vocal and manual reactive inhibitions and (3)
that proactive and reactive inhibitions would be positively related. We tested 14
participants over two sessions (one session with anodal tDCS and one session with
sham stimulation) and applied stimulation protocol in the middle of the session,
i.e. only during the second of three phases. We used a stop signal task across
two stop conditions: relevant and irrelevant stop conditions in which stopping
was required or ignored, respectively. We found that reactive inhibition was
faster during and immediately after anodal tDCS relative to sham. We also found
that greater level of proactive inhibition enhanced reactive inhibition (indexed
by shorter stop signal reaction times). These results support the hypothesis that
the right-PFC is part of a core network for reactive inhibition and supports
previous contention that proactive inhibition is possibly modulated via
preactivating the reactive inhibition network.
PMID- 26419663
TI - The nature of constant and cyclic force production: unintentional force-drift
characteristics.
AB - We explored unintentional changes in forces during performance of constant and
cyclic force-production tasks (F-tasks) after visual feedback removal. Based on
earlier studies, we expected all force parameters to drop exponentially with
time. We also explored possible role of working memory in the force drop
phenomena. Healthy subjects performed constant or cyclic isometric F-tasks with
the index finger under visual feedback. The cyclic task was paced by a metronome.
Removing visual feedback resulted in a consistent force drop in constant F-tasks
and a qualitatively similar drift in the mean force in the cyclic F-task. Both
were slow with characteristic times of about 10-20 s. In contrast, force
amplitude in the cyclic F-task increased quickly (within 1-2 s). When the
subjects were asked to stop producing force for 5 s after the visual feedback
disappeared and then resume force production, no downward force drift was seen in
constant F-tasks, while in cyclic F-tasks, the drift of the mean force was
present and an exaggerated increase in force amplitude was also observed. We
conclude that while working memory limitations may influence cyclic F-tasks,
their role in determining the force drift in constant F-tasks is limited. The
results of both experiments are interpreted within the referent configuration
hypothesis supplemented with an idea of unintentional drift of referent
coordinates (RC-back-coupling) induced by differences between the referent and
actual body configurations.
PMID- 26419665
TI - Circulating Levels of Uric Acid and Risk for Metabolic Syndrome.
AB - : Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases
renal excretion of uric acid, both mechanisms link elevated serum uric acid with
metabolic syndrome. The aim of this study is to evaluate the probability for the
development of metabolic syndrome in low-income young adults with hyperuricaemia.
METHODS: We evaluated 103 patients less than 40 years of age, from a low-income
population, and without history of cardiovascular disease, in all of them the
presence of metabolic syndrome was assessed in accordance with the International
Diabetes Federation criteria. In all patients, fasting serum uric acid levels
were measured; hyperuricaemia was defined as serum uric acid values 6.5 mg/dl in
men and 5.1 mg/dl in women. Statistical analysis was performed with odds ratio.
RESULTS: 83 of our patients (80.5%) suffered metabolic syndrome, the odds ratio
for the presence of metabolic syndrome in patients with hyperuricaemia was 5.1
(p=0.002, I.C 1.8- 14.5). When patients were evaluated by gender a significantly
association between hyperuricaemia and metabolic syndrome was found in women
(odds ratio 3.6, p=0.048, C.I. 1.0-12.9), and men (odds ratio 10.2, p= 0.015, IC
1.5-13.2). When uric acid was correlated with the components of metabolic
syndrome, we only found a positive correlation with waist circumference
(r=0.483). CONCLUSION: Our results showed a significant association between
hyperuricemia and metabolic syndrome in low-income young adults in Mexico. DR is
associated with estimated risk of CVD in type 2 diabetic patients.
PMID- 26419664
TI - Effects of prolonged patellar tendon vibration on force steadiness in quadriceps
femoris during force-matching task.
AB - The quadriceps femoris (QF) muscle group plays an essential role in human
movement, such as standing, walking and running. The ability to maintain a steady
force during physical activity of the human lower limb is important for mobility,
postural control and balance. Although prolonged mechanical vibration of the
muscle-tendon unit can moderate the efficacy of synaptic input from Ia afferent
onto the alpha-motor neuron pathway, the effect of prolonged tendon vibration on
fluctuations of knee extensor force has received little attention. The purpose of
the present study was to examine the effects of prolonged patellar tendon
vibration on the force steadiness of the QF muscle. Nine healthy men performed a
submaximal force-matching task involving isometric knee extension before and
after patellar tendon vibration or quiet seated rest (n = 7, control condition)
for 30 min. The target force was 2.5, 10 and 30 % of maximal voluntary
contraction (MVC). Surface electromyography (EMG) of the four QF synergists was
recorded and normalized to EMG amplitude during the MVC. The knee extension force
and the EMG amplitude of vastus medialis during the MVC were significantly
reduced after the vibration, but did not significantly decrease in the control
condition. Fluctuations of force and normalized EMG of individual QF muscles at
each submaximal force level did not significantly change after the vibration. We
conclude that prolonged patellar tendon vibration does not influence the force
steadiness of the QF muscle during an isometric force-matching task.
PMID- 26419666
TI - One-Pot Synthesis of Polysubstituted Spirofluorene-Indene via Ru(II)-Catalyzed [3
+ 2] Annulation and Intramolecular Friedel-Crafts Cyclization.
AB - Ru(II)-catalyzed one-pot synthesis of polysubstituted spirofluorene-indenes via
[3 + 2] annulation and then intramolecular Friedel-Crafts alkylation has been
achieved. The simple method provides a broad scope of aryl ketones and internal
alkynes, achieving PAHs skeletons in moderate to good yields.
PMID- 26419667
TI - Maternal and Peer Regulation of Adolescent Emotion: Associations with Depressive
Symptoms.
AB - Emotion socialization by close relationship partners plays a role in adolescent
depression. In the current study, a microsocial approach was used to examine how
adolescents' emotions are socialized by their mothers and close friends in real
time, and how these interpersonal emotion dynamics are related to adolescent
depressive symptoms. Participants were 83 adolescents aged 16 to 17 years who
participated in conflict discussions with their mothers and self-nominated close
friends. Adolescents' positive and negative emotions, and mothers' and peers'
supportive regulation of adolescent emotions, were coded in real time. Two
multilevel survival analyses in a 2-level Cox hazard regression framework
predicted the hazard rate of (1) mothers' supportive regulation of adolescents'
emotions, and (2) peers' supportive regulation of adolescents' emotions. The
likelihood of maternal supportiveness, regardless of adolescent emotions, was
lower for adolescents with higher depressive symptoms. In addition, peers were
less likely to up-regulate adolescent positive emotions at higher levels of
adolescent depressive symptoms. The results of the current study support
interpersonal models of depression and demonstrate the importance of real-time
interpersonal emotion processes in adolescent depressive symptoms.
PMID- 26419669
TI - Not Throwing Baby Out with the Bathwater.
PMID- 26419668
TI - A randomized double-blind, non-inferiority Phase II trial, comparing dapaconazole
tosylate 2% cream with ketoconazole 2% cream in the treatment of Pityriasis
versicolor.
AB - OBJECTIVES: The objective of this research was to evaluate the efficacy of a new
antifungal imidazole, dapaconazole tosylate, in the treatment of Pityriasis
versicolor (PV). DESIGN AND METHODS: Sixty patients with clinical and mycological
diagnosis of PV were randomly assigned to receive either 1 g dapaconazole
tosylate 2% cream or 1 g ketoconazole 2% cream. Treatments were applied once a
day for 28 days. A dermatologist evaluated efficacy and safety daily, and weekly
laboratorial tests were performed. The primary end point was a clinical and
mycological cure of lesions after 28 days of treatment. The secondary end point
was the time to clinical healing assessed by Kaplan-Meier analysis and Log-rank
testing. RESULTS: Fifty-three patients adhered to protocol rules. Clinical and
mycological cure was achieved in 84.6% (22/26) and 92.6% (25/27) of patients
treated with ketoconazole and dapaconazole, respectively (difference [effect
size] = 8.0%, Standard error of difference: 8.69%, 95% CI: -6.3 to 22.3%). Median
time to healing was 23.5 and 21 days for ketoconazole and dapaconazole,
respectively (p = 0.126). Adverse events occurred only in ketoconazole-treated
patients (13%; 4/30). CONCLUSION: Dapaconazole tosylate is non-inferior to
ketoconazole when used at a dose of 20 mg/day for 28 consecutive days for the
treatment of PV. Dapaconazole also demonstrated a good safety profile.
PMID- 26419671
TI - When a Tree Falls in the Woods: The Gravitropic Response in Poplar.
PMID- 26419670
TI - Discovery of a Unique Clp Component, ClpF, in Chloroplasts: A Proposed Binary
ClpF-ClpS1 Adaptor Complex Functions in Substrate Recognition and Delivery.
AB - Clp proteases are found in prokaryotes, mitochondria, and plastids where they
play crucial roles in maintaining protein homeostasis (proteostasis). The plant
plastid Clp machinery comprises a hetero-oligomeric ClpPRT proteolytic core, ATP
dependent chaperones ClpC and ClpD, and an adaptor protein, ClpS1. ClpS1 selects
substrates to the ClpPR protease-ClpC chaperone complex for degradation, but the
underlying substrate recognition and delivery mechanisms are currently unclear.
Here, we characterize a ClpS1-interacting protein in Arabidopsis thaliana, ClpF,
which can interact with the Clp substrate glutamyl-tRNA reductase. ClpF and ClpS1
mutually stimulate their association with ClpC. ClpF, which is only found in
photosynthetic eukaryotes, contains bacterial uvrB/C and YccV protein domains and
a unique N-terminal domain. We propose a testable model in which ClpS1 and ClpF
form a binary adaptor for selective substrate recognition and delivery to ClpC,
reflecting an evolutionary adaptation of the Clp system to the plastid proteome.
PMID- 26419672
TI - Leaf Growth Directionality Is Divergent and Involves a Conserved MicroRNA
Regulatory Module.
PMID- 26419673
TI - Cyclic fatigue resistance of D-RaCe, ProTaper, and Mtwo nickel-titanium
retreatment instruments after immersion in sodium hypochlorite.
AB - OBJECTIVES: The aim of this study was to investigate the effect of immersion in
sodium hypochlorite (NaOCl) on cyclic fatigue resistance of three different
rotary nickel-titanium (NiTi) retreatment files. MATERIAL AND METHODS: A total of
90 new ProTaper, D-RaCe, and Mtwo retreatment files were tested. Thirty files of
the same brand were randomly assigned to two groups (n = 15). Group 1 was no
immersion (control group) and 16 mm of group 2 instruments were immersed in 5 %
NaOCl at 37 degrees C for 5 min. All instruments were then tested for cyclic
fatigue. Resistance to cyclic fatigue was determined by counting the numbers of
cycles to failure in a 60 degrees curve with a 5-mm radius, recording the time
in seconds to fracture. Data were analyzed by two-way analysis of variance.
RESULTS: Resistance to cyclic fatigue decreased significantly for D-RaCe
retreatment files after immersion in NaOCl. ProTaper and Mtwo retreatment files
were not affected from immersion to NaOCl. D-RaCe retreatment instruments showed
better cyclic fatigue resistance than ProTaper and Mtwo retreatment instruments,
and the difference was statistically significant (p < 0.05). There was no
significant difference between ProTaper and Mtwo retreatment instrument groups (p
> 0.05). CONCLUSIONS: D-RaCe retreatment instruments had the highest cyclic
fatigue resistance among retreatment files tested in this study, but immersion to
NaOCl decreased the cyclic fatigue resistance of D-RaCe retreatment instrument.
CLINICAL RELEVANCE: It should be considered that cyclic fatigue resistance of D
RaCe can decrease in contact with NaOCl during the removal of canal filling
material.
PMID- 26419674
TI - Efficiency of powered systems for interproximal enamel reduction (IER) and enamel
roughness before and after polishing-an in vitro study.
AB - OBJECTIVE: This aims to evaluate the efficiency of three different powered
interproximal enamel reduction (IER) systems and to assess enamel roughness
before and after polishing using different polishing times. MATERIAL AND METHODS:
Four metal strips of the G5 ProLign Set (swissdentacare, SDC, Grancia,
Switzerland), four segmental discs of the ASR-Set 4594 and two sonic tips of the
SonicLine Set (both Gebr. Basseler GmbH & Co. KG, Komet, Lemgo, Germany) were
evaluated. Human extracted incisors served as the medium. Enamel reduction was
determined in five intervals of 15 s each. Polishing was performed for 15 and 30
s using the manufacturers' recommended polishing systems. Enamel roughness (Ra)
was quantitatively assessed by confocal laser scanning microscopy (CLSM).
RESULTS: Significant differences in terms of enamel reduction were found among
the working ends of all tested systems. The time needed to remove 0.1, 0.2 and
0.3 mm of enamel was determined. Surface analysis showed significantly higher
mean Ra values for nine out of ten working ends before polishing. This was still
the case for five working ends after 15 s and for two after 30 s of polishing.
CONCLUSION: The graining and the system used have a significant influence on
enamel reduction. The time needed for polishing depends on the last working end
used; a polishing time of 30 s is not always appropriate. CLINICAL RELEVANCE:
Knowledge about the cutting efficiency of powered IER working ends might help the
clinician to estimate better the amount of enamel reduction during the stripping
process.
PMID- 26419675
TI - Microbiological effects and recolonization patterns after adjunctive subgingival
debridement with Er:YAG laser.
AB - OBJECTIVES: The objective of this study was to assess the microbiological effects
and recolonization patterns after non-surgical periodontal treatment protocol
based on the adjunctive use of erbium-doped yttrium aluminium garnet (Er:YAG)
laser. MATERIAL AND METHODS: Patients diagnosed with chronic periodontitis were
randomly assigned to two different treatment protocols: test, full-mouth
subgingival ultrasonic instrumentation followed by Er-YAG laser application 1
week later to sites with initial probing pocket depth >=4.5 mm; and control, full
mouth ultrasonic subgingival instrumentation within 1 week. Clinical (at sampled
sites) and microbiological (culture-based) parameters were recorded at baseline
and 3 and 12 months. Microbiological variables included total counts, frequency
of detection, proportions and counts of target species. RESULTS: Results from 19
test and 21 control patients were compared. Minor changes were observed for total
colony-forming units, with no differences between groups. For the frequency of
detection, a limited and similar impact in both groups was observed for the most
prevalent (over 80 %) periodontal pathogens (Porphyromonas gingivalis, Prevotella
intermedia, Fusobacterium nucleatum). For proportions, reductions in P.
gingivalis occurred at 3 months, both in the test and control groups (from 16.3
to 10 % and 16 to 14.8 %, respectively), although these differences were not
statistically significant. At 12 months, the test group showed a statistically
significant greater reduction in probing depth for the sampled sites.
CONCLUSIONS: The adjunctive use of Er:YAG laser when compared with conventional
ultrasonic debridement did not provide a microbiological added benefit. CLINICAL
RELEVANCE: Even though some clinical benefits with the adjunctive laser
application were identified when comparing both treatment protocols, there were
no differences in microbiological outcomes or in the bacterial recolonization
patterns.
PMID- 26419677
TI - Implantable wireless battery recharging system for bladder pressure chronic
monitoring.
AB - This paper presents an implantable wireless battery recharging system design for
bladder pressure chronic monitoring. The wireless recharging system consists of
an external 15 cm-diameter 6-turn powering coil and a silicone-encapsulated
implantable rectangular coil with a dimension of 7 mm * 17 mm * 2.5 mm and 18
turns, which further encloses a 3 mm-diameter and 12 mm-long rechargeable
battery, two ferrite rods, an ASIC, and a tuning capacitor. For a constant
recharging current of 100 MUA, an RF power of 700 MUW needs to be coupled into
the implantable module through the tuned coils. Analyses and experiments confirm
that with the two coils aligned coaxially or with a 6 cm axial offset and a
tilting angle of 30 degrees , an external power of 3.5 W or 10 W is required,
respectively, at an optimal frequency of 3 MHz to cover a large implant depth of
20 cm.
PMID- 26419676
TI - Transungual permeation: current insights.
AB - Nail disorders are beyond cosmetic concern; besides discomfort in the performance
of daily chores, they disturb patients psychologically and affect their quality
of life. Fungal nail infection (onychomycosis) is the most prevalent nail-related
disorder affecting a major population worldwide. Overcoming the impenetrable nail
barrier is the toughest challenge for the development of efficacious topical
ungual formulation. Sophisticated techniques such as iontophoresis and
photodynamic therapy have been proven to improve transungual permeation. This
article provides an updated and concise discussion regarding the conventional
approach and upcoming novel approaches focused to alter the nail barrier. A
comprehensive description regarding preformulation screening techniques for the
identification of potential ungual enhancers is also described in this review
while highlighting the current pitfalls for the development of ungual delivery.
PMID- 26419678
TI - Ivabradine reduces myocardial stunning in patients with exercise-inducible
ischaemia.
AB - Ivabradine is an effective treatment for angina in patients with stable coronary
artery disease (CAD) and for heart failure. Experiments in a canine model have
shown that ivabradine reduces both acute left ventricular (LV) dysfunction and
post-ischaemic stunning. Aim of this study was to investigate the effect of
ivabradine on LV dysfunction and stunning in patients with CAD and exercise
inducible ischaemia. Fifteen patients with ejection fraction >40 % and heart rate
>70 bpm were enrolled. After pharmacologic washout, echocardiography was
performed at rest, at peak treadmill exercise and during recovery until return to
baseline. After 2 weeks of ivabradine (7.5 mg bid) stress echocardiography was
repeated at the same workload achieved during washout. Peak global and segmental
(ischaemic vs. remote normal segments) LV longitudinal strain (LS) was assessed
by 2D speckle tracking analysis. At washout, LS was significantly impaired in
ischaemic compared to remote segments at peak stress and for several minutes
during recovery. After ivabradine a smaller, albeit still significant, impairment
of LS in ischaemic segments was observed at peak whilst no difference with remote
segments was present during recovery. Furthermore, the average global LS value
improved significantly after treatment. In conclusion, ivabradine reduces both
acute LV dysfunction and stunning in patients with CAD and exercise-inducible
ischaemia. We hypothesise that this mechanism might contribute to reduce chronic
LV dysfunction in patients with CAD. In this setting the drug might limit the
development of hibernating myocardium which is believed to result from repeated
episodes of ischaemia and stunning.
PMID- 26419679
TI - Assessing risk factors for early hip osteoarthritis in activity-related hip pain:
a Delphi study.
AB - OBJECTIVE: Hip pain and injury as a result of activity can lead to the
development of early hip osteoarthritis (OA) in susceptible individuals. Our
understanding of the factors that increase susceptibility continues to evolve.
The ability to clearly identify individuals (and cohorts) with activity-related
hip pain who are at risk of early hip OA is currently lacking. The purpose of
this study was to gain expert consensus on which key clinical measures might help
predict the risk of early hip OA in individuals presenting with activity-related
hip pain. The agreed measures would constitute a standardised approach to initial
clinical assessment to help identify these individuals. METHODS: This Dephi study
used online surveys to gain concordance of expert opinion in a structured process
of 'rounds'. In this study, we asked 'What outcome measures are useful in
predicting hip OA in activity-related hip pain?' The Delphi panel consisted of
experts from sport and exercise medicine, orthopaedics, rheumatology,
physiotherapy and OA research. RESULTS: The study identified key clinical
measures in the history, examination and investigations (plain anteroposterior
radiograph and femoroacetabular impingement views) that the panel agreed would be
useful in predicting future risk of hip OA when assessing activity-related hip
pain. The panel also agreed that certain investigations and tests (eg, MR
angiography) did not currently have a role in routine assessment. There was a
lack of consensus regarding the role of MRI, patient-reported outcome measures
(PROMs) and certain biomechanical and functional assessments. CONCLUSIONS: We
provide a standardised approach to the clinical assessment of patients with
activity-related hip pain. Assessment measures rejected by the Delphi panel were
newer, more expensive investigations that currently lack evidence. Assessment
measures that did not reach consensus include MRI and PROMs. Their role remains
ambiguous and would benefit from further research.
PMID- 26419680
TI - Cost-effectiveness and budget impact of Empirical vitamin D therapy on
unintentional falls in older adults in the UK.
AB - OBJECTIVES: To evaluate the health outcomes and economics associated with the
current guidance relating to the prevention of falls in the elderly through
vitamin D supplementation. SETTING: UK. PARTICIPANTS: UK population aged 60 years
and above. INTERVENTIONS: A Markov health state transition model simulated
patient transitions between key fall-related outcomes using a 5-year horizon and
annual cycles to assess the costs and benefits of empirical treatment with
colecalciferol 800 iu daily. PRIMARY AND SECONDARY OUTCOME MEASURES: Costs and
health outcomes attributable to fall prevention following vitamin D
supplementation. RESULTS: Our model shows that treating the UK population aged 60
years and above with 800 iu colecalciferol would, over a 5-year period: (1)
prevent in excess of 430,000 minor falls; (2) avoid 190,000 major falls; (3)
prevent 1579 acute deaths; (4) avoid 84,000 person-years of long-term care and
(5) prevent 8300 deaths associated with increased mortality in long-term care.
The greatest gains are seen among those 75 years and older. Based on reduction in
falls alone, the intervention in all adults aged 65+ is cost-saving and leads to
increased quality adjusted life years. Treating all adults aged 60+ incurs an
intervention cost of L2.70bn over 5 years, yet produces a -L3.12bn reduction in
fall-related costs; a net saving of L420M. Increasing the lower bound age limit
by 5-year increments increases budget impact to -L1.17bn, -L1.75bn, and -L2.06bn
for adults 65+, 70+ and 75+, respectively. CONCLUSIONS: This study shows that
treatment of the elderly UK population with colecalciferol 800 iu daily would be
associated with reductions in mortality and substantial cost-savings through fall
prevention.
PMID- 26419681
TI - Multicentre, randomised, placebo-controlled trial of extract of Japanese herbal
medicine Daikenchuto to prevent bowel dysfunction after adult liver
transplantation (DKB 14 Study).
AB - INTRODUCTION: This multicentre randomised controlled clinical trial will aim to
determine the ability of an extract (TJ-100) of Daikenchuto (traditional Japanese
herbal medicine; Kampo) to prevent bowel dysfunction in at least 110 patients
after liver transplantation (LT). METHODS AND ANALYSIS: The following co-primary
end points will be evaluated on postoperative day 7: total oral and enteral
caloric intake, abdominal distension and abdominal pain. The secondary end points
will comprise sequential changes of total oral and enteral caloric intake after
LT, sequential changes in numeric rating scales for abdominal distension and
pain, elapsed time to the first postoperative passage of stool, quality of life
assessment using the Gastrointestinal Symptom Rating Scale score (Japanese
version), postoperative liver function, liver regeneration rate, incidence of
bacteraemia and bacterial strain, trough level of immunosuppressants, occurrence
of acute cellular rejection, discharge or not within 2 months after LT,
sequential changes of portal venous flow to the graft and ascites discharge. The
two arms of the study will comprise 55 patients per arm. ETHICS AND
DISSEMINATION: The study has been conducted according to the CONSORT statement.
All participants signed a written consent form, and the study has been approved
by the institutional review board of each participating institute and conducted
in accordance with the Declaration of Helsinki of 1996. The findings will be
disseminated through scientific and professional conferences, and in peer
reviewed journals. TRIAL REGISTRATION NUMBER: The DKB 14 Study was registered in
the University Hospital Medical Information Network Clinical Trial Registration
(UMIN-CTR), Japan (registration number: UMIN000014326) during 2014.
PMID- 26419682
TI - Gallstone is correlated with an increased risk of idiopathic sudden sensorineural
hearing loss: a retrospective cohort study.
AB - OBJECTIVES: This study aims to test the hypothesis that gallstone disease (GSD)
is a risk factor for the development of idiopathic sudden sensorineural hearing
loss (ISSNHL). Research has shown risks of cardiovascular and cerebrovascular
events in patients with GSD; however, well-conducted English studies on the
association between GSD and the development of ISSNHL are lacking. DESIGN AND
SETTING: Retrospective cohort study using the Taiwan Longitudinal Health
Insurance Database. PARTICIPANTS: We compared 26,449 patients diagnosed with GSD
between 1 January 2001 and 31 December 2007, with 52,898 age-matched, gender
matched and comorbidities propensity scores-matched controls. OUTCOME MEASURED:
We followed each patient until the end of 2011 and evaluated the incidence of
ISSNHL for at least 4 years after the initial GSD diagnosis. RESULTS: The
incidence of ISSNHL was 1.42 times higher in the GS cohort than in the non-GS
cohort (9.27 vs 6.52/10,000 person-years). Using Cox proportional hazard
regressions, the adjusted HR was 1.44 (95% CI 1.19 to 1.74). In the cohort of
patients with GSD who needed a cholecystectomy, 37 patients suffered from ISSNHL.
Among those patients, 31 (83.7%) patients sustained ISSNHL before cholecystectomy
and 6 (16.2%) patients sustained ISSNHL after cholecystectomy. CONCLUSIONS: A
diagnosis of GSD may be an independent risk for ISSNHL. This finding suggests
that an underlying vascular and inflammatory mechanism may contribute to the
development of ISSNHL. Physicians may want to counsel patients with GSD to seek
medical attention if they have hearing impairments, because patients may be at an
increased risk of developing ISSNHL.
PMID- 26419683
TI - The challenge of vaccinating adults: attitudes and beliefs of the Canadian public
and healthcare providers.
AB - OBJECTIVES: Vaccine coverage for recommended vaccines is low among adults. The
objective of this study was to assess the knowledge, attitudes, beliefs and
behaviours of adults and healthcare providers related to four vaccine-preventable
diseases and vaccines (diphtheria-tetanus-pertussis, zoster, pneumococcus and
influenza). DESIGN: We undertook a survey and focus groups of Canadian adults and
healthcare providers (doctors, nurses, pharmacists). A total of 4023 adults
completed the survey and 62 participated in the focus groups; 1167 providers
completed the survey and 45 participated in the focus groups. RESULTS: Only 46.3%
of adults thought they were up-to-date on their vaccines; 30% did not know. In
contrast, 75.6% of providers reported being up-to-date. Only 57.5% of adults
thought it was important to receive all recommended vaccines (compared to 87.1
91.5% of providers). Positive attitudes towards vaccines paralleled concern about
the burden of illness and confidence in the vaccines, with providers being more
aware of disease burden and confident in vaccine effectiveness than the public.
Between 55.0% and 59.7% of adults reported willingness to be vaccinated if
recommended by their healthcare provider. However, such recommendations were
variable; while 77.4% of the public reported being offered and 52.8% reported
being recommended the influenza vaccine by their provider, only 10.8% were
offered and 5.6% recommended pertussis vaccine. Barriers and facilitators to
improved vaccine coverage in adults, such as trust-mistrust of health
authorities, pharmaceutical companies and national recommendations, autonomy
versus the public good and logistical issues (such as insufficient time and lack
of vaccination status tracking), were identified by both the public and
providers. CONCLUSIONS: Despite guidelines for adult vaccination, there are
substantial gaps in knowledge and attitudes and beliefs among both the public and
healthcare providers that lead to low vaccine coverage. A systematic approach
that involves education, elimination of barriers and establishing and improving
infrastructure for adult immunisation is required.
PMID- 26419684
TI - Tracking Biases: An Update to the Validity and Reliability of Alcohol Retail
Sales Data for Estimating Population Consumption in Scotland.
AB - AIMS: To highlight the importance of monitoring biases when using retail sales
data to estimate population alcohol consumption. METHODS: Previously, we
identified and where possible quantified sources of bias that may lead to under-
or overestimation of alcohol consumption in Scotland. Here, we update findings by
using more recent data and by quantifying emergent biases. RESULTS:
Underestimation resulting from the net effect of biases on population consumption
in Scotland increased from -4% in 2010 to -7% in 2013. CONCLUSION: Biases that
might impact on the validity and reliability of sales data when estimating
population consumption should be routinely monitored and updated.
PMID- 26419685
TI - Coccidioidomycosis in Biopsies with Presumptive Diagnosis of Malignancy in Dogs:
Report of Three Cases and Comparative Discussion of Published Reports.
AB - Coccidioidomycosis is a respiratory fungal infection with occasional systemic
dissemination. The disseminated coccidioidomycosis is considered a multifaceted
disease. In medicine, disseminated coccidioidomycosis is included within a group
of infectious diseases that have been referred as the great imitators. In many
cases, malignancies are included in the presumptive diagnosis. In veterinary
medicine, disseminated coccidioidomycosis is common in dogs. Nonetheless, despite
of being a diagnostic dilemma, disseminated coccidioidomycosis is underestimated
and frequently not included into differentials, even in endemic zones. Herein, we
describe three cases of granulomatous inflammation caused by Coccidioides spp.
which were masquerading malignancies in dogs (0.39 %). The presumptive diagnoses
in these cases were osteosarcoma, lymphoma and neurofibroma, respectively. A PCR
assay employing tissues in paraffin blocks resulted positive for C. posadasii in
one of these cases. A comparative discussion on the ambiguous clinic-pathological
presentation of disseminated coccidioidomycosis in dogs and humans is included.
PMID- 26419686
TI - Coffee inhibits nuclear factor-kappa B in prostate cancer cells and xenografts.
AB - Chronic inflammation contributes to prostate cancer and the transcription factor
Nuclear Factor-kappa B (NF-kappaB) is constitutively active in most such cancers.
We examine the effects of coffee on NF-kappaB and on the regulation of selected
genes in human-derived prostate cancer cells (PC3) and in PC3 xenografts in
athymic nude mice. PC3 cells stably transduced with an NF-kappaB-luciferase
reporter were used both in vitro and for xenografts. NF-kappaB activity was
measured by reporter assays, DNA binding and in vivo imaging. Gene expression was
measured in PC3 cells, xenografts and tumor microenvironment by low-density
arrays. Western blotting of activated caspases was used to quantify apoptosis.
Coffee inhibited TNFalpha-induced NF-kappaB activity and DNA-binding in PC3
cells. Furthermore, coffee increased apoptosis and modulated expression of a
number of inflammation- and cancer-related genes in TNFalpha-treated PC3 cells.
In vivo imaging revealed a 31% lower NF-kappaB-luciferase activation in the
xenografts of the mice receiving 5% coffee compared to control mice.
Interestingly, we observed major changes in gene expression in the PC3 cells in
xenografts as compared to PC3 cells in vitro. In PC3 xenografts, genes related to
inflammation, apoptosis and cytoprotection were down-regulated in mice receiving
coffee, and coffee also affected the gene expression in the xenograft
microenvironment. Our data demonstrate that coffee inhibits NF-kappaB activity in
PC3 cells in vitro and in xenografts. Furthermore, coffee modulates transcription
of genes related to prostate cancer and inflammation. Our results are the first
to suggest mechanistic links between coffee consumption and prostate cancer in an
experimental mouse model.
PMID- 26419688
TI - Intramolecular Excimer Formation Dynamics of 1,3-Bis-(1-pyrenyl)propane within 1
Butyl-3-methylimidazolium Hexafluorophosphate and Its Polyethylene Glycol
Mixtures.
AB - Mixtures of ionic liquid with polyethylene glycol (PEG) have shown interesting
features as solubilizing media. Intramolecular excimer formation dynamics of 1,3
bis-(1-pyrenyl)propane [1Py(3)1Py] is investigated within mixtures of a common
and popular ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate
([bmim][PF6]) with PEGs of average molecular weight (MW) 200 (PEG200), average MW
400 (PEG400), number-average MW Mn 570-630 (PEG600), and number-average MW Mn 950
1050 (PEG1000) over the complete composition range at a 10 degrees interval in
the temperature range 10-90 degrees C. Irrespective of the composition of the
medium and the temperature, excited-state intensity decay of the excimer
fluorescence best fits to a three-exponential decay function, suggesting the
presence of one excited-state monomer and two kinetically distinguishable
excimers where both excimers are populated simultaneously by the excited monomer
with no interconversion between the two excimers. In neat PEGs for temperatures
<= 50 degrees C, intensity decay data of monomer fluorescence best fits to a
single-exponential decay function, which implies the dissociation of both
excimers back to the monomer to be insignificant. As the temperature is
increased, the fits become closer to a double-exponential decay function,
implying dissociation of one of the excimers to become significant. In neat
[bmim][PF6], while a double-exponential decay function is required to fit the
monomer excited-state intensity decay data at lower temperatures, three
exponentials are required to satisfactorily fit the data at higher temperatures,
suggesting both excimers significantly dissociate back to the monomer at higher
temperatures within the ionic liquid. Within long-chain PEG-containing
([bmim][PF6] + PEG) mixtures, PEG as opposed to [bmim][PF6] controls the excimer
formation dynamics by supposedly wrapping around the excimer, thus hindering
dissociation back to the monomer. The overall rate constant of the excimer
formation within ([bmim][PF6] + PEG) mixtures is found to scale better with the
microviscosity rather than the bulk viscosity of the mixtures.
PMID- 26419689
TI - Few-Volt Operation of Printed Organic Ferroelectric Capacitor.
AB - The fabrication of single-crystalline thin-film arrays for an organic
ferroelectric small molecule is achieved by a simple solution process without
additional thermal annealing. Based on a cooperative proton tautomerism through a
hydrogen-bonding network, films show the polarity switching with an operating
voltage of less than 5 V at room temperature. This approach provides a low-cost
and eco-friendly fabrication of ferroelectric devices.
PMID- 26419690
TI - Effect of ceftriaxone and cefepime on high-dose methotrexate clearance.
AB - Numerous drug interactions with methotrexate have been identified, which can lead
to serious life-threatening effects. Up to 90% of methotrexate is excreted
unchanged in the urine with primary excretion dependent on organic anion
transport in the renal proximal tubule. The two pathways responsible for
methotrexate secretion are organic anion transport 1 and primarily organic anion
transport 3. Penicillins undergo tubular secretion via organic anion transport,
and cephalosporins are believed to also possess a similar risk when administered
with methotrexate; however, there are no human studies observing this interaction
with cephalosporins and methotrexate. Ceftriaxone undergoes biliary clearance and
has low affinity for the same organic anion transports as methotrexate;
therefore, ceftriaxone has a low potential to interact with methotrexate.
Cefepime is primarily secreted by organic cation transport N2, and also has a low
potential to interact with methotrexate. This case report describes the
pharmacokinetic effect of concomitant beta-lactam therapy in a patient receiving
high-dose methotrexate.
PMID- 26419691
TI - Impact of oncology pharmacist-managed oral anticancer therapy in patients with
chronic myelogenous leukemia.
AB - BACKGROUND: Studies have identified non-adherence as one of the major
contributing factors to treatment failure in chronic myelogenous leukemia (CML)
patients receiving imatinib. Published literature has demonstrated a unique role
of oncology pharmacists, as part of a multidisciplinary team, in contributing to
overall positive outcomes for patients. STUDY OBJECTIVE: To evaluate the impact
of an oncology pharmacist-managed oral anticancer therapy program on oral
medication adherence in CML patients versus usual care. METHODS: Electronic
refill history and medical records of patients diagnosed with CML treated with
oral tyrosine kinase inhibitors (TKIs) managed by oncology pharmacists during a 6
year period, were retrospectively reviewed. Imatinib adherence rate, as the
primary endpoint, was compared with the rate for those in the usual care group
within the same organization. The secondary endpoints were descriptive to
characterize pharmacist interventions for all TKIs. RESULTS: A total of 56
patients including 45 who were treated with imatinib, were evaluated. The group
managed by oncology pharmacists resulted in a higher percentage of imatinib
adherence rate compared to usual care (88.6% vs 65.8%, p = 0.0046). A total of
3432 pharmacist encounters were reviewed, and 567 interventions of six categories
including side effect monitoring/management (n = 95; 16.8%); drug interaction
detection (n = 109; 19.2%); TKI dose adjustment (n = 82; 14.5%); laboratory
monitoring (n = 200; 35.3%); non-CML related drug choice (n = 74; 13.1%); and
copay assistance (n = 7; 1.2%), were documented. This resulted in a mean of 10.1
interventions per patient. CONCLUSIONS: Our oncology pharmacist-managed oral
anticancer therapy program significantly improved TKI adherence rates in CML
patients. We attribute the success of our program to consistent follow-up by
utilizing routine phone, and secure email follow-ups, that allowed our oncology
pharmacists to build a close and trustworthy relationship with patients and
families.
PMID- 26419692
TI - Cytarabine syndrome despite corticosteroid premedication in an adult undergoing
induction treatment for acute myelogenous leukemia.
AB - Cytarabine syndrome is a rare clinical condition characterized by fever, malaise,
myalgia, arthralgia, and/or rash that occurs after receipt of cytarabine. Our
patient developed fever, malaise, and diffuse body pain shortly following
cytarabine initiation despite receiving prophylactic dexamethasone. The patient's
discomfort was treated with intravenous morphine and her other symptoms were
controlled with a higher dose of dexamethasone. Although the exact cause is not
fully understood, cytarabine syndrome is hypothesized to be an immune-mediated
response following cytarabine-induced apoptosis that results in a rapid increase
in proinflammatory cytokines. While there is no standard therapy for cytarabine
syndrome, corticosteroids appear to play a role in the treatment and prevention
of the condition by suppressing the proinflammatory response. Since our case
describes the development of cytarabine syndrome despite dexamethasone,
clinicians should monitor for this adverse event if patients begin exhibiting
characteristics of this syndrome.
PMID- 26419687
TI - The complexity of the Nrf2 pathway: beyond the antioxidant response.
AB - The NF-E2-related factor 2 (Nrf2)-mediated signalling pathway provides living
organisms an efficient and pivotal line of defensive to counteract environmental
insults and endogenous stressors. Nrf2 coordinates the basal and inducible
expression of antioxidant and Phase II detoxification enzymes to adapt to
different stress conditions. The stability and cellular distribution of Nrf2 is
tightly controlled by its inhibitory binding protein Kelch-like ECH-associated
protein 1. Nrf2 signalling is also regulated by posttranslational,
transcriptional, translational and epigenetic mechanisms, as well as by other
protein partners, including p62, p21 and IQ motif-containing GTPase activating
protein 1. Many studies have demonstrated that Nrf2 is a promising target for
preventing carcinogenesis and other chronic diseases, including cardiovascular
diseases, neurodegenerative diseases and pulmonary injury. However, constitutive
activation of Nrf2 in advanced cancer cells may confer drug resistance. Here, we
review the molecular mechanisms of Nrf2 signalling, the diverse classes of Nrf2
activators, including bioactive nutrients and other chemicals, and the cellular
functions and disease relevance of Nrf2 and discuss the dual role of Nrf2 in
different contexts.
PMID- 26419693
TI - Salt-Free Reduction of Nonprecious Transition-Metal Compounds: Generation of
Amorphous Ni Nanoparticles for Catalytic C-C Bond Formation.
AB - A salt-free procedure for the generation of a wide variety of metal(0) particles,
including Fe, Co, Ni, and Cu, was achieved using 2,3,5,6-tetramethyl-1,4
bis(trimethylsilyl)-1,4-diaza-2,5-cyclohexadiene (1), which reduced the
corresponding metal precursors under mild conditions. Notably, Ni particles
formed in situ from the treatment of Ni(acac)2 (acac = acetylacetonate) with 1 in
toluene exhibited significant catalytic activity for reductive C-C bond-forming
reactions of aryl halides in the presence of excess amounts of 1. By examination
of high-magnification transmission electron microscopy images and electron
diffraction patterns, we concluded that amorphous Ni nanoparticles (Ni aNPs) were
essential for the high catalytic activity.
PMID- 26419694
TI - Heat and oxidative stress alter the expression of orexin and its related
receptors in avian liver cells.
AB - Orexins (A and B) or hypocretins (1 and 2) are hypothalamic orexigenic
neuropeptides that are involved in the regulation of several physiological
processes in mammals. Recently, orexin has been shown to activate the
hypothalamic-pituitary-adrenal (HPA) stress axis and emerging evidences identify
it as a stress modulator in mammals. However, the regulation of orexin system by
stress itself remains unclear. Here, we investigate the effects of heat, 4
Hydroxynonenal (4-HNE) and hydrogen peroxide (H2O2) stress on the hepatic
expression of orexin (ORX) and its related receptors (ORXR1/2) in avian species.
Using in vivo and in vitro models, we found that heat stress significantly down
regulated ORX and ORXR1/2 mRNA and protein abundances in quail liver and LMH
cells. H2O2, however, decreased ORX protein and increased ORX mRNA levels in a
dose dependent manner (P<0.05). The absence of correlation between orexin mRNA
and protein levels suggests that H2O2 treatment modulates post-transcriptional
mechanisms. 4-HNE had a biphasic effect on orexin system expression, with a
significant up-regulation at low doses (10 and 20MUM) and a significant down
regulation at a high dose (30MUM). Taken together, our data indicated that
hepatic orexin system could be a molecular signature in the heat and oxidative
stress response.
PMID- 26419695
TI - Energy metabolism of hyperthyroid gilthead sea bream Sparus aurata L.
AB - Thyroid hormones, in particular 3,5,3'-triiodothyronine or T3, are involved in
multiple physiological processes in mammals such as protein, fat and carbohydrate
metabolism. However, the metabolic actions of T3 in fish are still not fully
elucidated. We therefore tested the effects of T3 on Sparus aurata energy
metabolism and osmoregulatory system, a hyperthyroid-induced model that was
chosen. Fish were implanted with coconut oil depots (containing 0, 2.5, 5.0 and
10.0MUg T3/g body weight) and sampled at day 3 and 6 post-implantation. Plasma
levels of free T3 as well as glucose, lactate and triglyceride values increased
with increasing doses of T3 at days 3 and 6 post-implantation. Changes in plasma
and organ metabolite levels (glucose, glycogen, triglycerides, lactate and total
alpha amino acid) and enzyme activities related to carbohydrate, lactate, amino
acid and lipid pathways were detected in organs involved in metabolism (liver)
and osmoregulation (gills and kidney). Our data implicate that the liver uses
amino acids as an energy source in response to the T3 treatment, increasing
protein catabolism and gluconeogenic pathways. The gills, the most important
extruder of ammonia, are fuelled not only by amino acids, but also by lactate.
The kidney differs significantly in its substrate preference from the gills, as
it obtained metabolic energy from lactate but also from lipid oxidation
processes. We conclude that in S. aurata lipid catabolism and protein turnover
are increased as a consequence of experimentally induced hyperthyroidism, with
secondary osmoregulatory effects.
PMID- 26419696
TI - Plasma levels of follicle-stimulating and luteinizing hormones during the
reproductive cycle of wild and cultured Senegalese sole (Solea senegalensis).
AB - The intensive culture of the Senegalese sole (Solea senegalensis) is hampered by
the low or null fertilization rates exhibited by the first generation (F1) of
reared males. To investigate the regulation of the reproductive processes in this
species by the pituitary gonadotropins follicle-stimulating and luteinizing
hormones (Fsh and Lh, respectively), we developed a highly sensitive and specific
enzyme-linked immunosorbent assay (ELISA) for Lh measurements. Quantification of
the Fsh and Lh plasma levels in cultured sole using the Lh ELISA developed here,
and a previously developed ELISA for Fsh, indicated that in both males and
females circulating Fsh steadily increased during autumn and winter and prior to
the major spawning in spring, whereas an Lh surge occurred specifically during
spawning. The increase in Fsh was associated with a rise of plasma levels of the
steroid hormones testosterone (T), 11-ketotestosterone (11-KT) and estradiol
17beta (E2), but that of Lh was concomitant with a strong decline of the levels
of E2 in females and of 11-KT in males, possibly reflecting a rapid steroidogenic
shift promoting the final maturation of gametes. Comparison of the plasma levels
of gonadotropins and steroids between wild and F1 fish during autumn and spring
revealed that F1 males showed significantly lower plasma Lh titres compared to
wild males, whereas the levels of T and 11-KT were similar or more elevated in
the F1 fish. These data suggest that an impaired Lh secretion during spawning,
and perhaps altered Lh-mediated mechanisms in the testis, may be underlying
causes for the low reproductive performance of Senegalese sole F1 males.
PMID- 26419697
TI - Developmental expression of estrogen receptor beta in the brain of prairie voles
(Microtus ochrogaster).
AB - Here, for the first time, the expression of estrogen receptor beta (ERbeta) is
characterized in the brains of the highly prosocial prairie vole (Microtus
ochrogaster). ERbeta immunoreactivity was compared in weanlings (postnatal Day
21) and adult males and females. The results indicate several major findings.
First, unlike ERalpha, ERbeta expression is not sexually dimorphic. Second, the
adult pattern of ERbeta-IR is established at the time of weaning, as there were
no age-dependent effects on distribution. Finally, ERbeta does not appear to be
as widely distributed in voles compared with rats and mice. High levels of ERbeta
IR were observed in several regions/nuclei within the medial pre-optic area,
ventrolateral pre-optic nuclei, and in the hypothalamus, especially in the
paraventricular and supraoptic nuclei. The visualization of ERbeta in prairie
voles is important as the socially monogamous prairie vole functions as a human
relevant model system for studying the expression of social behavior and social
deficit disorders. Future studies will now be able to determine the effect of
treatments on the expression and/or development of ERbeta in this highly social
species.
PMID- 26419698
TI - Synergistic effect of exogeneous and endogeneous electrostimulation on osteogenic
differentiation of human mesenchymal stem cells seeded on silk scaffolds.
AB - Bioelectrical regulation of bone fracture healing is important for many cellular
events such as proliferation, migration, and differentiation. The aim of this
study was to investigate the osteogenic differentiation potential of human
mesenchymal stem cells (hMSCs) cultivated on silk scaffolds in response to
different modes of electrostimulation (e.g., exogeneous and/or endogeneous).
Endogeneous electrophysiology was altered through the use of monensin (10 nM) and
glibenclamide (10 MUM), along with external electrostimulation (60 kHz; 100-500
mV). Monensin enhanced the expression of early osteogenic markers such as
alkaline phosphatase (ALP) and runt-related transcription factor 2 (RUNX-2). When
exogeneous electrostimulation was combined with glibenclamide, more mature
osteogenic marker upregulation based on bone sialoprotein expression (BSP) and
mineralization was found. These results suggest the potential to exploit both
exogeneous and endogeneous biophysical control of cell functions towards tissue
specific goals.
PMID- 26419699
TI - Ultra-processed foods have the worst nutrient profile, yet they are the most
available packaged products in a sample of New Zealand supermarkets--CORRIGENDUM.
PMID- 26419700
TI - Music, empathy and cultural understanding.
AB - In the age of the Internet and with the dramatic proliferation of mobile
listening technologies, music has unprecedented global distribution and
embeddedness in people's lives. It is a source of intense experiences of both the
most intimate and solitary, and public and collective, kinds - from an individual
with their smartphone and headphones, to large-scale live events and global
simulcasts; and it increasingly brings together a huge range of cultures and
histories, through developments in world music, sampling, the re-issue of
historical recordings, and the explosion of informal and home music-making that
circulates via YouTube. For many people, involvement with music can be among the
most powerful and potentially transforming experiences in their lives. At the
same time, there has been increasing interest in music's communicative and
affective capacities, and its potential to act as an agent of social bonding and
affiliation. This review critically discusses a considerable body of research and
scholarship, across disciplines ranging from the neuroscience and psychology of
music to cultural musicology and the sociology and anthropology of music, that
provides evidence for music's capacity to promote empathy and social/cultural
understanding through powerful affective, cognitive and social factors; and
explores ways in which to connect and make sense of this disparate evidence (and
counter-evidence). It reports the outcome of an empirical study that tests one
aspect of those claims, demonstrating that 'passive' listening to the music of an
unfamiliar culture can significantly change the cultural attitudes of listeners
with high dispositional empathy; presents a model that brings together the
primary components of the music and empathy research into a single framework; and
considers both some of the applications, and some of the shortcomings and
problems, of understanding music from the perspective of empathy.
PMID- 26419701
TI - Significant factors for work attractiveness and how these differ from the current
work situation among operating department nurses.
AB - AIMS AND OBJECTIVES: The aim was to examine significant factors for work
attractiveness and how these differ from the current work situation among
operating department nurses. A second objective was to examine the associations
between age, gender, length of employment, work engagement, work ability, self
rated health indicators and attractiveness of the current work situation.
BACKGROUND: The attractiveness of work is rarely taken into account in research
on nurse retention. To expand this knowledge, it is relevant to examine factors
that make work attractive and their associations with related concepts. DESIGN:
Correlational, cross-sectional survey using a convenience sample. METHODS:
Questionnaires were answered by 147 nurses in four operating departments in
Sweden. Correlation and regression analyses were conducted. RESULTS: The nurses
rated the significance of all factors of work attractiveness higher than they
rated those factors in their current work situation; salary, organisation and
physical work environment had the largest differences. The most significant
attractive factors were relationships, leadership and status. A statistically
significant positive correlation between work engagement and attractive work was
found. In the multiple regression model, the independent variables work
engagement and older age significantly predicted work attractiveness.
CONCLUSIONS: Several factors should be considered in the effort to increase work
attractiveness in operating departments and thereby to encourage nurse retention.
Positive aspects of work seem to unite work engagement and attractive work, while
work ability and self-rated health indicators are other important dimensions in
nurse retention. RELEVANCE TO CLINICAL PRACTICE: The great discrepancies between
the significance of attractive factors and the current work situation in salary,
organisation and physical work environment suggest ways in which work
attractiveness may be increased. To discover exactly what needs to be improved
may require a deeper look into the construct of the examined factors.
PMID- 26419702
TI - Quantifying barcodes of dendritic spines using entropy-based metrics.
AB - Spine motility analysis has become the mainstay for investigating synaptic
plasticity but is limited in its versatility requiring complex, non automatized
instrumentations. We describe an entropy-based method for determining the spatial
distribution of dendritic spines that allows successful estimation of spine
motility from still images. This method has the potential to extend the
applicability of spine motility analysis to ex vivo preparations.
PMID- 26419703
TI - Estimation of genetic parameters for carcass defects of Japanese Black cattle in
Kagoshima.
AB - Cattle exhibit a range of carcass defects, including blood splash (BLS),
intramuscular edema (INE), muscle steatosis (MUS), bruising (BR), trim loss (TRL)
and others (OTH). These defects lower the carcass value and can result in
significant economic loss to producers. We estimated the incidence, relationship
with inbreeding coefficients and genetic parameters of carcass defects in
Japanese Black cattle using 561 619 carcass records from Kagoshima, Japan during
April 1988 through March 2011. The defect incidence ranged from 0.22% for TRL to
5.73% for BR. The incidence of MUS and BR increased from 1.21% to 6.57% and from
1.06% to 9.31%, respectively. The incidence of INE peaked at 7.44% in 1999 and
decreased thereafter. We observed a positive linear relationship between the
defect incidence and the inbreeding coefficients in MUS, BR and TRL (P < 0.01).
The heritabilities estimated by univariate animal model with Gibbs sampling for
BLS, INE, MUS, BR and TRL were 0.24, 0.06, 0.18, 0.05 and 0.02, respectively. The
contribution of farm variance to phenotypic variance was negligible (0.01 to
0.04). Significant genetic correlations of TRL were estimated with MUS (0.63) and
BR (0.63). Our results suggest that genetic factors contribute to the incidence
of BLS and MUS.
PMID- 26419704
TI - Kidney-specific Sonoporation-mediated Gene Transfer.
AB - Sonoporation can deliver agents to target local organs by systemic
administration, while decreasing the associated risk of adverse effects.
Sonoporation has been used for a variety of materials and in a variety of organs.
Herein, we demonstrated that local sonoporation to the kidney can offer highly
efficient transfer of oligonucleotides, which were systemically administrated to
the tubular epithelium with high specificity. Ultrasonic wave irradiation to the
kidney collapsed the microbubbles and transiently affected the glomerular
filtration barrier and increased glomerular permeability. Oligonucleotides were
passed through the barrier all at once and were absorbed throughout the tubular
epithelium. Tumor necrosis factor alpha (TNFalpha), which plays a central role in
renal ischemia-reperfusion injury, was targeted using small interfering RNA
(siRNA) with renal sonoporation in a murine model. The reduction of TNFalpha
expression after single gene transfer significantly inhibited the expression of
kidney injury markers, suggesting that systemic administration of siRNA under
temporary and local sonoporation could be applicable in the clinical setting of
ischemic acute kidney injury.
PMID- 26419708
TI - The contribution of allied health professionals.
PMID- 26419706
TI - Metabolome analysis reveals the effect of carbon catabolite control on the
poly(gamma-glutamic acid) biosynthesis of Bacillus licheniformis ATCC 9945.
AB - Poly(gamma-glutamic acid) (PGA) is a polymer composed of L- and/or D-glutamic
acids that is produced by Bacillus sp. Because the polymer has various features
as water soluble, edible, non-toxic and so on, it has attracted attention as a
candidate for many applications such as foods, cosmetics and so on. However,
although it is well known that the intracellular metabolism of Bacillus sp. is
mainly regulated by catabolite control, the effect of the catabolite control on
the PGA producing Bacillus sp. is largely unknown. This study is the first report
of metabolome analysis on the PGA producing Bacillus sp. that reveals the effect
of carbon catabolite control on the metabolism of PGA producing Bacillus
licheniformis ATCC 9945. Results showed that the cells cultivated in glycerol
containing medium showed higher PGA production than the cells in glucose
containing medium. Furthermore, metabolome analysis revealed that the activators
of CcpA and CodY, global regulatory proteins of the intracellular metabolism,
accumulated in the cells cultivated in glycerol-containing and glucose-containing
medium, respectively, with CodY apparently inhibiting PGA production. Moreover,
the cells seemed to produce glutamate from citrate and ammonium using glutamine
synthetase/glutamate synthase. Pulsed addition of di-ammonium hydrogen citrate,
as suggested by the metabolome result, was able to achieve the highest value so
far for PGA production in B. licheniformis.
PMID- 26419707
TI - Electronic Topological Transition in Ag2Te at High-pressure.
AB - Recently, Ag2Te was experimentally confirmed to be a 3D topological insulator
(TI) at ambient pressure. However, the high-pressure behaviors and properties of
Ag2Te were rarely reported. Here, a pressure-induced electronic topological
transition (ETT) is firstly found in Ag2Te at 1.8 GPa. Before ETT, the positive
pressure coefficient of bulk band-gap, which is firstly found in TIs family, is
found by both first-principle calculations and in situ high-pressure resistivity
measurements. The electrical resistivity obtained at room temperature shows a
maximum at 1.8 GPa, which is nearly 3.3 times to that at ambient pressure. This
result indicates that the best bulk insulating character and topological nature
in Ag2Te can be obtained at this pressure. Furthermore, the high-pressure
structural behavior of Ag2Te has been investigated by in situ high-pressure
synchrotron powder X-ray diffraction technique up to 33.0 GPa. The accurate
pressure-induced phase transition sequence is firstly determined as P21/c -> Cmca
-> Pnma. It is worth noting that the reported isostructural P21/c phase is not
existed, and the reported structure of Cmca phase is corrected by CALYPSO
methodology. The second high-pressure structure, a long puzzle to previous
reports, is determined as Pnma phase. A pressure-induced metallization in Ag2Te
is confirmed by the results of temperature-dependent resistivity measurements.
PMID- 26419705
TI - A RIAM/lamellipodin-talin-integrin complex forms the tip of sticky fingers that
guide cell migration.
AB - The leading edge of migrating cells contains rapidly translocating activated
integrins associated with growing actin filaments that form 'sticky fingers' to
sense extracellular matrix and guide cell migration. Here we utilized indirect
bimolecular fluorescence complementation to visualize a molecular complex
containing a Mig-10/RIAM/lamellipodin (MRL) protein (Rap1-GTP-interacting adaptor
molecule (RIAM) or lamellipodin), talin and activated integrins in living cells.
This complex localizes at the tips of growing actin filaments in lamellipodial
and filopodial protrusions, thus corresponding to the tips of the 'sticky
fingers.' Formation of the complex requires talin to form a bridge between the
MRL protein and the integrins. Moreover, disruption of the MRL protein-integrin
talin (MIT) complex markedly impairs cell protrusion. These data reveal the
molecular basis of the formation of 'sticky fingers' at the leading edge of
migrating cells and show that an MIT complex drives these protrusions.
PMID- 26419709
TI - Prevention of surgical site infection: compliance is key.
PMID- 26419710
TI - The application of epic3 guidelines: the complexity of practice.
AB - Healthcare-associated infection (HCAI) is a major patient safety concern and is
associated with morbidity, mortality and increased healthcare costs. Prevention
and control requires a multi-modal approach, but the individual's accountability
and rigorous application of standard infection prevention and control behaviours
is at its core. The third instalment of the epic3 guidance ( Loveday et al, 2014a
) provided the evidence and advanced the importance of hand-hygiene behaviour,
the use of non-sterile gloves and environmental cleanliness. This discussion
considers some of the recommendations made in these areas of practice and some of
the underlying complexities. Producing guidelines based on the best available
evidence and transforming them into policies can be a useful adjunct to
communicating the necessary standards. However, policies often erase the
complexity of implementation. To strive for the best possible standard is an
understandable and laudable objective, but organisations need to be mindful of
the difficulties and obstacles that stand in their way, particularly in an era
where the philosophy of 'zero tolerance' is gaining popularity.
PMID- 26419711
TI - Letter to the Editor.
AB - The editorial in BJN 24(15) written by BJN Editor in Chief, Ian Peate, challenged
the Nursing and Midwifery Council's (NMC) Chief Executive and Registrar's
assertion that the progress her organisation has achieved over the past 12 months
is something to be 'delighted' about. The NMC responded and their letter is
below. If you would like to comment on the issue email us:
bjn@markallengroup.com.
PMID- 26419712
TI - Sepsis: contemporary issues and implications for nursing.
PMID- 26419713
TI - A multicentred cohort evaluation of a chitosan gelling fibre dressing.
AB - A multicentre cohort evaluation was undertaken by 15 clinicans in 11 centres
across Staffordshire community care on chitosan gelling fibre dressing
(Kytocel((r))). The aim of this evaluation was to examine whether the new fibre
dressing improved healing outcomes for patients with chronic non-healing wounds
of 6 weeks or more, observations were made regarding tissue type, fluid handling,
haemostasis in bleeding friable wounds and increased granulation. Quality of life
observations regarding leaking, strikethrough, pain, wear time and malodour were
observed over a 4-week period or until healed. A total of 18 patients took part;
13 women and 5 men, with a mean age of 60.7 years. Fifteen (83%) had wounds in
excess of 12 weeks and nine (50%) received care within wound clinics compared to
home visits. Eleven (61%) patients' wounds healed within 4 weeks. A number of
quality-of-life issues were addressed successfully, namely reduction in malodour
and fluid handling. Sixteen (89%) rated the dressing's overall performance as
very good to good.
PMID- 26419714
TI - Infection Prevention and Control Award: BJN RUNNER UP.
PMID- 26419715
TI - The impact of nurse prescribing on the clinical setting.
AB - AIM: To investigate the impact nurse prescribing has on the organisation, patient
and health professional, and to identify factors associated with the growth of
nurse prescribing. METHODS: Systematic search and narrative review. Data obtained
through CINAHL, PubMed, Science direct, Online Computer Library Centre (OCLC),
databases/websites, and hand searching. English peer-reviewed quantitative,
qualitative and mixed-method articles published from September 2009 through to
August 2014 exploring nurse prescribing from the perspective of the organisation,
health professional and patient were included. Following a systematic selection
process, studies identified were also assessed for quality by applying Cardwell's
framework. RESULTS: From the initial 443 citations 37 studies were included in
the review. Most studies were descriptive in nature. Commonalities addressed were
stakeholders' views, prescribing in practice, jurisdiction, education and
benefits/barriers. CONCLUSIONS: Prescriptive authority for nurses continues to be
a positive addition to clinical practice. However, concerns have emerged
regarding appropriate support, relationships and jurisdictional issues. A more
comprehensive understanding of nurse and midwife prescribing workloads is
required to capture the true impact and cost-effectiveness of the initiative.
PMID- 26419716
TI - Technology and the issues facing nursing assessment.
AB - This article describes an investigation into the use of technology and the issues
nurses face undertaking nursing assessment. It reports qualitative, descriptive
research involving interviews with ten ward nurses from three hospitals in New
Zealand. Thematic analysis of the data revealed three key issues: the impact of
technology, the influence of early warning systems and nurse autonomy. Results
show how clinical decision making around nursing assessment is influenced by
technology and the Early Warning Score. These clinical decisions may not always
be informed by critical thinking in complex healthcare environments. The article
concludes that nurse autonomy, while supported and endorsed in theory, is
frequently in conflict with hospital risk-management policies and the use of
prescriptive algorithms.
PMID- 26419717
TI - Learning not blaming: the Government response.
AB - In this second of a two-part column, John Tingle discusses the Government's
response to the consultation on the Freedom to Speak Up review, the report
Investigating Clinical Incidents in the NHS, and The Report of the Morecambe Bay
Investigation.
PMID- 26419718
TI - Focus on people, not the system: improving the NHS in England.
AB - Emeritus professor Alan Glasper, from the University of Southampton, discusses
the launch of the latest Department of Health initiative to make the NHS more
people-focused, rather than system-focused.
PMID- 26419719
TI - Patient information: confidentiality and the electronic record.
AB - The rise of the electronic record now allows nurses to access a large archive of
patient information that was more difficult to obtain when records consisted of
manually held paper files. There have been several instances where curiosity and,
occasionally, more malicious motivations have led nurses to access these records
and read the notes of a celebrity or a person they know. In this article, Richard
Griffith considers whether nurses' accessing and reading of the record of someone
who is not in their care is in breach of their duty of confidentiality.
PMID- 26419720
TI - The importance of education for a new primary care workforce.
PMID- 26419721
TI - Examining the role of personal traumas in a nurse's work life.
AB - In this monthly column, Aysha Mendes discusses the impact a nurse's personal
traumas can have on his or her nursing practice, professional and personal
experience of caring, and on patients and their families.
PMID- 26419722
TI - Writing for publication: from staff nurse to nurse consultant.
PMID- 26419723
TI - Learning from patients using the goldfish bowl model.
PMID- 26419724
TI - Targeting substrate-site in Jak2 kinase prevents emergence of genetic resistance.
AB - Emergence of genetic resistance against kinase inhibitors poses a great challenge
for durable therapeutic response. Here, we report a novel mechanism of JAK2
kinase inhibition by fedratinib (TG101348) that prevents emergence of genetic
resistance. Using in vitro drug screening, we identified 211 amino-acid
substitutions conferring resistance to ruxolitinib (INCB018424) and cross
resistance to the JAK2 inhibitors AZD1480, CYT-387 and lestaurtinib. In contrast,
these resistant variants were fully sensitive to fedratinib. Structural modeling,
coupled with mutagenesis and biochemical studies, revealed dual binding sites for
fedratinib. In vitro binding assays using purified proteins showed strong
affinity for the substrate-binding site (Kd = 20 nM) while affinity for the ATP
site was poor (Kd = ~8 MUM). Our studies demonstrate that mutations affecting the
substrate-binding pocket encode a catalytically incompetent kinase, thereby
preventing emergence of resistant variants. Most importantly, our data suggest
that in order to develop resistance-free kinase inhibitors, the next-generation
drug design should target the substrate-binding site.
PMID- 26419726
TI - Notch signaling dynamics in the adult healthy prostate and in prostatic tumor
development.
AB - BACKGROUND: The Notch signaling pathway has been implicated in prostate
development, maintenance and tumorigenesis by its key role in cell-fate
determination, differentiation and proliferation. Therefore, we proposed to
analyze Notch family members transcription and expression, including ligands
(Dll1, 3, 4 and Jagged1 and 2), receptors (Notch1-4) and effectors (Hes1, 2, 5
and Hey1, 2, L), in both normal and tumor bearing mouse prostates to better
understand the dynamics of Notch signaling in prostate tumorigenesis. METHODS:
Wild type mice and transgenic adenocarcinoma of the mouse prostate model (TRAMP)
mice were sacrificed at 18, 24 or 30 weeks of age and the prostates collected and
processed for either whole prostate or prostate cell specific populations mRNA
analysis and for protein expression analysis by immunohistochemistry and
immunofluorescence. RESULTS: We observed that Dll1 and Dll4 are expressed in the
luminal compartment of the mouse healthy prostate, whereas Jagged2 expression is
restricted to the basal and stromal compartment. Additionally, Notch2 and Notch4
are normally expressed in the prostate luminal compartment while Notch2 and
Notch3 are also expressed in the stromal layer of the healthy prostate. As
prostate tumor development takes place, there is up-regulation of Notch
components. Particularly, the prostate tumor lesions have increased expression of
Jagged1 and 2, of Notch3 and of Hey1. We have also detected the presence of
activated Notch3 in prostatic tumors that co-express Jagged1 and ultimately the
Hey1 effector. CONCLUSIONS: Taken together our results point out the Notch axis
Jagged1-2/Notch3/Hey1 to be important for prostate tumor development and worthy
of additional functional studies and validation in human clinical disease.
PMID- 26419727
TI - Environmental roles of microbial amino acid racemases.
AB - Enzymes catalysing the stereo-chemical inter-conversion of amino acids are known
as amino acid racemases. In bacteria, these enzymes are fundamental to synthesize
the D-Ala and D-Glu that are critical components of the peptidoglycan. In
addition to this structural function in cell wall assembly, D-amino acids
produced by microbial amino acid racemases have been described as relevant
constituents in other prokaryotic structures (e.g. capsule, non-ribosomal
peptides) and have been associated to growth fitness and to processes such as
biofilm development, spore germination and signalling. The recent discovery of
broad spectrum racemases able to produce and release several D-amino acids to the
environment suggests that these enzymes might have a great impact in microbial
ecology. Consequently, new data on the biochemistry and regulation of racemases
is key to understand the biological significance of D-enantiomers in nature, in
particular their effect on microbial social networks. This review summarizes
current knowledge on the environmental roles of bacterial racemases with an
emphasis on the potential roles of the new broad spectrum enzymes in natural
environments.
PMID- 26419728
TI - In situ detection of salicylate in Ocimum basilicum plant leaves via reverse
iontophoresis.
AB - The quantitative analysis of salicylate provides useful information for the
evaluation of metabolic processes in plants. We report a simple, noninvasive
method to measure salicylate in situ in Ocimum basilicum leaves using reverse
iontophoresis in combination with cyclic voltammetry at disposable screen-printed
electrodes and the concentration of salicylate in basil leaves was found to be 3
mM.
PMID- 26419725
TI - The complexity of epigenetic diseases.
AB - Over the past 30 years, a plethora of pathogenic mutations affecting enhancer
regions and epigenetic regulators have been identified. Coupled with more recent
genome-wide association studies (GWAS) and epigenome-wide association studies
(EWAS) implicating major roles for regulatory mutations in disease, it is clear
that epigenetic mechanisms represent important biomarkers for disease development
and perhaps even therapeutic targets. Here, we discuss the diversity of disease
causing mutations in enhancers and epigenetic regulators, with a particular focus
on cancer.
PMID- 26419729
TI - 17p11.2 and Xq28 duplication detected in a girl diagnosed with Potocki-Lupski
syndrome.
AB - BACKGROUND: Potocki-Lupski syndrome is a microduplication syndrome associated
with duplication at 17p11.2. Features include facial dysmorphism, moderate to
mild cognitive impairment and behavioural abnormalities including autism spectrum
disorders. CASE PRESENTATION: We describe a patient from Sri Lanka that was
referred for genetic assessment at 4 years of age due to subtle facial
dysmorphism and expressive language impairment. She was diagnosed with Potocki
Lupski syndrome through multiplex ligation probe amplification. She carried two
duplications; one in 17p11.2 consistent with Potocki-Lupski, and one in Xq
including the region for X-linked intellectual disability. CONCLUSION: Despite
the absence of expected behavioural symptoms, many features of this patient are
in accordance with Potocki-Lupski syndrome. This is the first diagnosed patient
in Sri Lanka.
PMID- 26419730
TI - Lipopeptide biosurfactant viscosin enhances dispersal of Pseudomonas fluorescens
SBW25 biofilms.
AB - Pseudomonads produce several lipopeptide biosurfactants that have antimicrobial
properties but that also facilitate surface motility and influence biofilm
formation. Detailed studies addressing the significance of lipopeptides for
biofilm formation and architecture are rare. Hence, the present study sets out to
determine the specific role of the lipopeptide viscosin in Pseudomonas
fluorescens SBW25 biofilm formation, architecture and dispersal, and to relate
viscA gene expression to viscosin production and effect. Initially, we compared
biofilm formation of SBW25 and the viscosin-deficient mutant strain
SBW25DeltaviscA in static microtitre assays. These experiments demonstrated that
viscosin had little influence on the amount of biofilm formed by SBW25 during the
early stages of biofilm development. Later, however, SBW25 formed significantly
less biofilm than SBW25DeltaviscA. The indication that viscosin is involved in
biofilm dispersal was confirmed by chemical complementation of the mutant
biofilm. Furthermore, a fluorescent bioreporter showed that viscA expression was
induced in biofilms 4 h prior to dispersal. Subsequent detailed studies of
biofilms formed in flow cells for up to 5 days revealed that SBW25 and
SBW25DeltaviscA developed comparable biofilms dominated by well-defined, mushroom
shaped structures. Carbon starvation was required to obtain biofilm dispersal in
this system. Dispersal of SBW25 biofilms was significantly greater than of
SBW25DeltaviscA biofilms after 3 h and, importantly, carbon starvation strongly
induced viscA expression, in particular for cells that were apparently leaving
the biofilm. Thus, the present study points to a role for viscosin-facilitated
motility in dispersal of SBW25 biofilms.
PMID- 26419731
TI - Video-based on-ward supervision for final year medical students.
AB - BACKGROUND: Constructive feedback is an essential element of the educational
process, helping trainees reach their maximum potential and increasing their
skill level. Video-based feedback has been described as highly effective in
various educational contexts. The present study aimed to evaluate the feasibility
and acceptability of video-based, on-ward supervision for final year students in
a clinical context with real patients. METHODS: Nine final year medical students
(three male, six female; aged 25.1 +/- 0.7 years) and eight patients (five male,
three female; aged 59.3 +/- 16.8 years) participated in the pilot study. Final
year students performed routine medical procedures at bedside on internal
medicine wards at the University of Heidelberg Medical Hospital. Students were
filmed and were under supervision. After performing the procedures, an oral
feedback loop was established including student, patient and supervisor feedback
on communicative and procedural aspects of skills performed. Finally, students
watched their video, focusing on specific teachable moments mentioned by the
supervisor. Written evaluations and semi-structured interviews were conducted
that focused on the benefits of video-based, on-ward supervision. Interviews were
analysed qualitatively, using open coding to establish recurring themes and
overarching categories to describe patients' and students' impressions.
Descriptive, quantitative analysis was used for questionnaire data. RESULTS:
Supervised, self-chosen skills included history taking (n = 6), physical
examination (n = 1), IV cannulation (n = 1), and ECG recording (n = 1). The video
based, on-ward supervision was well accepted by patients and students. Supervisor
feedback was rated as highly beneficial, with the video material providing an
additional opportunity to focus on crucial aspects and to further validate the
supervisor's feedback. Students felt the video material would be less beneficial
without the supervisor's feedback. The setting was rated as realistic, with
filming not influencing behaviour. CONCLUSION: Video-based, on-ward supervision
may be a powerful tool for improving clinical medical education. However, it
should be regarded as an additional tool in combination with supervisors' oral
feedback. Acceptance was high in both students and patients. Further research
should address possibilities of efficiently combining and routinely establishing
these forms of feedback in medical education.
PMID- 26419732
TI - Anticholinergic Exposure During Rehabilitation: Cognitive and Physical Function
Outcomes in Patients with Delirium Superimposed on Dementia.
AB - OBJECTIVES: We examined the association between anticholinergic medication
exposure and subsequent cognitive and physical function in patients with delirium
superimposed on dementia during rehabilitation. We also examined length of stay
and discharge disposition by anticholinergic medication exposure. DESIGN: In this
secondary analysis we used control group data from an ongoing randomized clinical
trial. SETTING/PARTICIPANTS: Participants with delirium and dementia were
enrolled at admission to post-acute care. These 99 participants had a mean age of
86.11 (+/-6.83) years; 67.6% were women; 98% were Caucasian; and 33% were
positive for at least one APOE e4 allele. MEASURES: We obtained daily measures of
cognitive and physical function using: Digit Span; memory, orientation and
attention items from the Montreal Cognitive Assessment; CLOX; the Confusion
Assessment Method; and the Barthel Index. Anticholinergic medication exposure was
measured weekly using the Anticholinergic Cognitive Burden Scale. RESULTS: Using
multilevel models for time we found that greater use of clinically relevant
anticholinergic medications in the previous week reduced cognitive and physical
function, as measured by Digit Span Backwards and the Barthel index, in the
current week. There was no effect of anticholinergic medication use on delirium
severity, and APOE status did not moderate any outcomes. Greater use of
clinically relevant anticholinergic medications was related to longer length of
stay but not discharge disposition. CONCLUSIONS: For vulnerable older adults,
anticholinergic exposure represents a potentially modifiable risk factor for poor
attention, working memory, physical function, and greater length of stay during
rehabilitation.
PMID- 26419733
TI - Age-Related Macular Degeneration-Associated Genes in Alzheimer Disease.
AB - OBJECTIVES: Given the clinical and pathological similarities between age-related
macular degeneration (AMD) and Alzheimer disease (AD), to assess whether AMD
associated single nucleotide polymorphisms (SNPs), including those from
complement-related genes, are associated with AD. DESIGN: A case-control
association study-type design. SETTING: A UK tertiary care dementia clinic.
PARTICIPANTS: 322 cognitively normal participants and 258 cases with a clinical
diagnosis of AD. MEASUREMENTS: Polymorphisms in the following genes were studied:
CFH, ARMS2, C2/CFB, C3, CFI/PLA2G12a, SERPING1, TLR3, TLR4, CRP, APOE, and
TOMM40. Haplotypes were analysed for CFH, TOMM40, and APOE. Univariate analysis
was performed for each genetic change and case-comparator status, and then
correction for multiple testing performed. RESULTS: The presence of an epsilon4
APOE allele was significantly associated with AD. No association was evident
between CFH SNPs or haplotypes, or other AMD-associated SNPs tested, and AD. The
exceptions were TOMM40 SNPs, which were associated with AD even after correction
for multiple comparisons. The associations disappeared, however, when entered
into a regression model including APOE genotypes. CONCLUSIONS: The results for
most SNPs tested, as well as CFH haplotypes, are novel. The functional effects of
abnormal complement activity in AD's pathogenesis may be contradictory, but
methodological reasons may underlie the lack of association-for example, genetic
changes other than SNPs being involved.
PMID- 26419734
TI - Risk of Hospitalization for Hypoglycemia in Older Patients with Diabetes Using
Antipsychotic Drugs.
AB - OBJECTIVE: Antipsychotics may disrupt metabolic regulation in patients with
diabetes mellitus. The risk of hypoglycemia in older users of antipsychotics with
diabetes is largely unknown. Therefore, we investigated the association between
the use of antipsychotic drugs and hypoglycemia requiring hospital admission in
older patients with diabetes. METHODS: In a nested case-control study using
community pharmacy records linked to hospital admission data in the Netherlands
(1998-2008), a cohort of 68,314 patients at least 65 years with diabetes was
studied. Cases were patients from the study cohort with a first hospital
admission for hypoglycemia; up to five comparison subjects were selected for each
case. Exposure to antipsychotic drugs was the primary determinant of interest.
Logistic regression analysis was performed to estimate the strength of the
association between antipsychotic drug use and hypoglycemia, taking into account
potential confounders. RESULTS: Eight hundred fifteen patients were admitted to
hospital for hypoglycemia. Current use of antipsychotic drugs was associated with
an increased risk of hypoglycemia compared with non-use (adjusted OR: 2.26; 95%
CI: 1.45-3.52; Wald chi(2) = 13.08, df = 1, p <=0.001), especially in the first
30 days of treatment (adjusted OR: 7.65; 95% CI: 2.50-23.41; Wald chi(2) = 12.72,
df = 1, p <=0.001) and with higher doses (adjusted OR: 8.20; 95% CI: 3.09-21.75;
Wald chi(2) = 17.90, df = 1, p <=0.001). CONCLUSION: Use of antipsychotic drugs
by older patients with diabetes mellitus was associated with an increased risk of
hospitalization for hypoglycemia. Our findings suggest that glucose levels should
be monitored closely after initiation of antipsychotic drugs.
PMID- 26419735
TI - Effectiveness of the Modified Instrumental Reminiscence Intervention on
Psychological Well-Being Among Community-Dwelling Chinese Older Adults: A
Randomized Controlled Trial.
AB - OBJECTIVE: The current study aimed to examine the effectiveness of the
Instrumental Reminiscence Intervention-Hong Kong (IRI-HK) on alleviating
depressive symptoms and improving life satisfaction in Chinese older adults
living in empty nests (i.e., living alone or with a spouse only) in the
community. METHODS: A longitudinal, randomized, controlled design was adopted.
Experimental and wait-list control groups were provided with the IRI-HK
immediately and 12 weeks after the baseline assessment, respectively.
Participants were 114 older adults living in empty nests and recruited via local
elderly community centers. This high-risk population with detectable depressive
symptoms were randomized into experimental (N = 46) and control (N = 68) groups.
The IRI-HK is a group reminiscence intervention modified with cultural
adaptations for Chinese older adults. It emphasizes the use of problem-focused
coping strategies and comprises six intervention sessions and two follow-up
sessions. Participants' depressive symptoms and life satisfaction were measured
by the Chinese version of the Geriatric Depression Scale-Short Form and the Life
Satisfaction Scale-Chinese, respectively. RESULTS: Findings from this study
showed a significant difference in depressive symptoms between groups after the
intervention, F(1,77) = 35.62, p <0.001. Life satisfaction of the experimental
group after the second follow-up was found to be significantly higher than that
of the control group, F(1,68) = 5.67, p <0.05. CONCLUSION: The IRI-HK was a
successful cultural adaption suitable for use in the Chinese context. It was
found to be an effective intervention for alleviating depressive symptoms in
older adults living in empty nests in the community.
PMID- 26419736
TI - The iron component of particulate matter is antiapoptotic: A clue to the
development of lung cancer after exposure to atmospheric pollutants?
AB - The classification of outdoor air pollution as carcinogenic for humans
strengthens the increasing concern about particulate matter (PM). We previously
demonstrated that PM exposure produces an antiapoptotic effect resulting from
polycyclic aromatic hydrocarbons (PAH) and water-soluble components. In this
study, we investigated transition metallic compounds, particularly iron, in order
to decipher their underlying molecular mechanisms that prevent apoptosis. Human
bronchial epithelial cells were exposed for 4 h to different PM samples with
established antiapoptotic effect (e.g. PM-AW) or not (e.g. PM-VS) or to their
metallic components (Fe, Mn, Zn and Al) before apoptosis induction by the calcium
ionophore A23187 or Staurosporine. PM-AW, Fe, Mn and Al significantly reduced
induced apoptosis. The antiapoptotic effect of Fe was enhanced by benzo(a)pyrene,
a typical PAH compound, but was totally reversed by the iron chelator,
deferiprone. Furthermore, particles and iron triggered cellular ROS generation
and prevented the depletion in glutathione levels observed during A23187-induced
apoptosis. In contrast to benzo(a)pyrene, PM-AW and Fe rapidly activated NRF2,
subsequently upregulated several target genes (HO1, NQO1 and GPX1) and modulated
some genes which control cell death (BCL2, BAX and p53). The key role of the NRF2
pathway in the antiapoptotic effect mediated by Fe and PM was demonstrated using
siRNA technology. Our results suggest that the iron component participates in the
antiapoptotic effect of PM by activating a NRF2-dependent antioxidant process. As
resisting to cell death is one of the hallmarks of cancer cells, these findings
provide additional clues for understanding the development of lung cancer after
atmospheric pollution exposure.
PMID- 26419737
TI - Association of matrix metalloproteinase-10 polymorphisms with susceptibility to
pelvic organ prolapse.
AB - AIM: The aim of this study was to explore the correlation between genetic
mutations in matrix metalloproteinase-10 (MMP-10) and susceptibility to pelvic
organ prolapse (POP). MATERIAL AND METHODS: From September 2011 to December 2013,
263 subjects were recruited, including 91 patients with POP (case group) and 172
non-POP patients (control group). Total MMP-10 concentrations in serum were
measured by enzyme-linked immunosorbent assay. The genotyping of MMP-10 was
achieved by quantitative real-time polymerase chain reaction. All data were
analyzed with SPSS 18.0. RESULTS: We found that parity, menopause, history of
total hysterectomy, and family history of POP were all significantly higher in
the POP group than in the control group (P = 0.017, P = 0.046, P = 0.0029 and P <
0.001, respectively). Serum MMP-10 levels were obviously higher in the POP group
than in the control group (P < 0.05). In addition, there was a statistically
significant difference between the two groups in the distribution frequency of
the MMP-10 (rs17435959G/C) genotype (P < 0.05). However, the distribution
frequency of the MMP-10 (rs17293607C/T) genotype between the two groups showed no
significant differences (P > 0.05). Furthermore, the patients with parity > 2 and
postmenopausal women had elevated serum MMP-10 levels, and the patients with
parity > 2 and postmenopausal women who carried the G/C + C/C genotype in the MMP
10 gene had an increased risk of POP. CONCLUSION: We support the view that the
rs17435959 polymorphism of the MMP-10 gene may be associated with an increased
risk of POP.
PMID- 26419738
TI - A reconstruction approach in wavelet domain for fluorescent molecular tomography
via rotated sources illumination.
AB - BACKGROUND: Fluorescent molecular tomography (FMT) aims at reconstructing the
spatial map of optical and fluorescence parameters from fluence measurements.
Basically, solving large-scale matrix equations is computationally expensive for
image reconstruction of FMT. Despite the reconstruction quality can be improved
with more sources, it may result in higher computational costs for
reconstruction. This article presents a novel method in the wavelet domain with
rotated sources illumination. METHODS: We use the finite element method for the
computation of the forward model. The global inverse problem is solved based on
wavelet in conjunction with principal component analysis. The iterative
reconstruction is implemented with sources rotated in a certain angle. The
original excitation light sources are used to reconstruct the image in the first
iteration. Then, upon the sources are rotated by a certain angle, they are
employed for the next iteration of reconstruction. RESULTS: Simulation results
demonstrate that our method can considerably reduce the time taken for the
computation of inverse problem in FMT. Furthermore, the approach proposed is also
shown to largely outperform the traditional method in terms of the precision of
inverse solutions. CONCLUSIONS: Our method has the capability to locate the
inclusions. The proposed method can significantly speed up the reconstruction
process with the high reconstruction quality.
PMID- 26419739
TI - Is an insecure job better for health than having no job at all? A systematic
review of studies investigating the health-related risks of both job insecurity
and unemployment.
AB - BACKGROUND: Though previous research repeatedly found that being employed is
better for health than having no job at all, evidence suggests that employment is
not always beneficial for health. With especially job insecurity reflecting a
contemporary health risk for the employed, a systematic review was performed to
assess if insecure employment can be as detrimental for health as unemployment,
and to determine whether these associations vary according to different health
measures and among men and women. METHODS: The literature search was conducted in
the databases Medline, Embase and PsychInfo. In order to allow a more accurate
comparison between the two risk factors, studies were included if the data for
job insecurity and unemployment was ascertained from the same sample, and
contained a quantitative analysis for both exposures towards one (or more) health
outcome(s). RESULTS: Out of 375 articles, in total, 13 studies were included in
the systematic review. In 24 analyses contrasting the health-related associations
between job insecurity and unemployment, 16 statistically significant
associations were found for each exposure. According to the different health
outcomes used, job insecurity and unemployment were strongly related to mental
health, whereas job insecurity was more strongly associated with somatic
symptoms. Unemployment showed stronger relations with worse general health and
mortality. In 4 out of 16 gender-stratified analyses, significant associations
between job insecurity/unemployment and health were found for men but not for
women. Beyond that, associations were significant or insignificant in both gender
groups. CONCLUSIONS: Though there were moderate differences across the health
outcomes, overall, it was found that job insecurity can pose a comparable threat
to health than unemployment. Policy interventions should therefore not only
consider health risks posed by unemployment, but should also aim at the reduction
of insecure employment.
PMID- 26419741
TI - Relationship between polyunsaturated fatty acid levels in maternal diets and
human milk in the first month post-partum.
AB - BACKGROUND: The present study evaluated the relationship between dietary fatty
acid (FA) intakes and human milk FA levels. METHODS: Healthy lactating women (n =
514) from Northern China participated in the study. Dietary intake was assessed
with a 24-h dietary recall questionnaire and evaluated using golden key maternal
nutrition software (Wincome, Shanghai, China) and China Food Composition 2009.
Human milk FA composition was determined by gas chromatography. RESULTS: The
maternal daily median intakes of linoleic acid (LA), alpha-linolenic acid (ALA)
and arachidonic acid (AA) were 19.93 g, 3.08 g and 16.33 mg, respectively.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes were below the
recommended levels. FA levels in 100 g of human milk were 0.363 g LA, 0.038 g
gamma-linolenic acid (GLA), 0.052 g dihomo gamma-linolenic acid (DGLA), 0.144 g
ALA, 0.079 g AA, 0.007 g EPA, 0.018 g docosatetraenoic acid (DTA) and 0.048 g
DHA. Multiple linear regression analysis revealed that human milk DGLA levels
were negatively correlated with dietary LA intake (beta = -0.223, P = 0.030), and
human milk GLA and DTA levels were negatively correlated with dietary ALA intake
(beta = -2.189, P = 0.031; beta = -2.252, P = 0.027) after adjusting for possible
confounding factors. CONCLUSIONS: The results of the present study suggest the
presence of competitive interactions between n-3 fatty acids (ALA) and n-6 fatty
acids (GLA and DTA).
PMID- 26419740
TI - Heterogeneity of aquaporin-4 localization and expression after focal cerebral
ischemia underlies differences in white versus grey matter swelling.
AB - INTRODUCTION: Ischemic stroke, a major cause of mortality, is frequently
accompanied by life-threatening cerebral edema. Aquaporin-4 (Aqp4), an astrocytic
transmembrane water channel, is an important molecular contributor to cerebral
edema formation. Past studies of Aqp4 expression and localization after ischemia
examined grey matter exclusively. However, as white matter astrocytes differ
developmentally, physiologically, and molecularly from grey matter astrocytes, we
hypothesized that functionally important regional heterogeneity exists in Aqp4
expression and subcellular localization following cerebral ischemia. RESULTS:
Subcellular localization of Aqp4 was compared between cortical and white matter
astrocytes in postmortem specimens of patients with focal ischemic stroke versus
controls. Subcellular localization and expression of Aqp4 was examined in rats
subjected to experimental stroke. Volumetric analysis was performed on the cortex
and white matter of rats subjected to experimental stroke. Following cerebral
ischemia, cortical astrocytes exhibited reduced perivascular Aqp4 and unchanged
Aqp4 protein abundance. In contrast, white matter astrocytes exhibited increased
perivascular and plasmalemmal Aqp4 and a 2.2- to 6.2-fold increase in Aqp4
isoform abundance. Ischemic white matter swelled by approximately 40 %, while
cortex swelled by approximately 9 %. CONCLUSIONS: The findings reported here
raise the possibility that cerebral white matter may play a heretofore
underappreciated role in the formation of cerebral edema following ischemia.
PMID- 26419743
TI - Trait and state binge eating predispose towards cocaine craving.
AB - Binge eating (BE) and drug seeking share similar behavioral features, including
loss of control over consumption and compulsive seeking of the craved substance.
Previous studies in animal models have demonstrated a complex interaction between
'state' BE, produced by intermittent access to a palatable diet, and 'trait' BE,
a phenotypical proneness towards overeating. In the present study, we examined
the relationship between state and trait BE and cocaine seeking. We used Otsuka
Long Evans Tokushima Fatty rats, a genetic model for obesity that demonstrates BE
like behavior, and Long Evans Tokushima Otsuka controls. They received a schedule
of limited access to a palatable diet (3 days/week or 5 days/week access to
Ensure for a month). Next, they underwent cocaine self-administration training (1
mg/kg, 1 hour/day for 10 days) followed by extinction sessions (7 days). We found
that the degree of BE-like behavior and the state and trait BE combination
predicted cocaine craving patterns. Lower levels of dopamine D2 receptors in the
prefrontal cortex were correlated with increased drug craving. Moreover,
restricted access to an attractive diet was found to be a risk factor for
heightened cocaine craving, particularly in trait binge eaters, as rats on the 3
days/week access schedule persistently failed to cease cocaine seeking throughout
extinction. Hence, we postulate a joint role of state and trait BE as risk
factors for heightened cocaine craving.
PMID- 26419742
TI - Myocardial SPECT Images in Incident Hemodialysis Patients Without Ischemic Heart
Disease.
AB - Cardiovascular disease is the leading cause of death in dialysis patients and is
significantly associated with poor survival in incident dialysis patients.
However, little is known about the pathogenesis of cardiovascular disease in
these populations. (123) I-15-(p-iodophenyl)-3(R,S)- methylpentadecanoic acid
(BMIPP) imaging is useful for detection of ischemic heart disease. We examined
imaging characteristics to identify potential pathologies of cardiac disease,
other than ischemic heart disease. The subjects were 42 incident dialysis
patients without histories of ischemic heart disease such as acute coronary
syndrome. All the patients underwent BMIPP imaging in addition to a screening
examination. Patients with positive findings in BMIPP imaging underwent
myocardial perfusion imaging within 2 weeks after BMIPP imaging to evaluate the
possibility of ischemic heart disease. Twenty-two patients were BMIPP-positive
and 10 of these patients had negative findings on perfusion imaging and were
defined as mismatch cases. Compared with patients who were BMIPP- and perfusion
positive, the mismatch cases had higher parathyroid hormone (PTH), serum albumin,
and alkaline phosphatase levels. The mismatch cases also formed the largest
proportion in the highest PTH tertile. A histologic examination of a mismatch
case with no stenotic lesions in the coronary artery revealed the presence of
cardiac hypertrophy and fibrosis. These findings suggest that a perfusion
metabolism mismatch may be present in incident dialysis patients without a
history of ischemic heart disease. This mismatch is associated with PTH, which
suggests potential involvement of uremic cardiomyopathy in the pathology of
cardiac disease in these patients.
PMID- 26419745
TI - Advanced Cd(II) complexes as high efficiency co-sensitizers for enhanced dye
sensitized solar cell performance.
AB - This work reports on two new complexes with the general formula
[Cd3(IBA)3(Cl)2(HCOO)(H2O)]n (1) and {[Cd1.5(IBA)3(H2O)6].3.5H2O}n (2), which can
be synthesized by the reaction of Cd(II) with rigid linear ligand 4-HIBA
containing imidazolyl and carboxylate functional groups [4-HIBA = 4-(1H-imidazol
1-yl)benzoic acid]. Single-crystal X-ray diffraction analyses indicate that
complex 1 is a 2D "wave-like" layer structure constructed from trinuclear units
and complex 2 is just a mononuclear structure. Surprisingly, both complexes 1 and
2 appear as a 3D supramolecular network via intermolecular hydrogen bonding
interactions. What's more, due to their strong UV-visible absorption, 1 and 2 can
be employed as co-sensitizers in combination with N719 to enhance dye-sensitized
solar cell (DSSC) performance. Both of them could overcome the deficiency of the
ruthenium complex N719 absorption in the region of ultraviolet and blue-violet,
and the charge collection efficiency is also improved when 1 and 2 are used as co
sensitizers, which are all in favor of enhancing the performance. The DSSC
devices using co-sensitizers of 1/N719 and 2/N719 show an overall conversion
efficiency of 8.27% and 7.73% with a short circuit current density of 17.48 mA
cm(-2) and 17.39 mA cm(-2), and an open circuit voltage of 0.75 V and 0.74 V,
respectively. The overall conversion efficiency is 27.23% and 18.92% higher than
that of a device solely sensitized by N719 (6.50%). Consequently, the prepared
complexes are high efficiency co-sensitizers for enhancing the performance of
N719 sensitized solar cells.
PMID- 26419744
TI - Cardiac rehabilitation.
PMID- 26419746
TI - Treatment of industrial effluents by electrochemical generation of H2O2 using an
RVC cathode in a parallel plate reactor.
AB - Electrochemical techniques have been used for the discolouration of synthetic
textile industrial wastewater by Fenton's process using a parallel plate reactor
with a reticulated vitreous carbon (RVC) cathode. It has been shown that RVC is
capable of electro-generating and activating H2O2 in the presence of Fe(2+) added
as catalyst and using a stainless steel mesh as anode material. A catholyte
comprising 0.05 M Na2SO4, 0.001 M FeSO4.7H2O, 0.01 M H2SO4 and fed with oxygen
was used to activate H2O2.The anolyte contained only 0.8 M H2SO4. The operating
experimental conditions were 170 mA (2.0 V < DeltaECell < 3.0 V) to generate 5.3
mM H2O2. Synthetic effluents containing various concentrations (millimolar - mM)
of three different dyes, Blue Basic 9 (BB9), Reactive Black 5 (RB5) and Acid
Orange 7 (AO7), were evaluated for discolouration using the electro-assisted
Fenton reaction. Water discolouration was measured by UV-VIS absorbance
reduction. Dye removal by electrolysis was a function of time: 90% discolouration
of 0.08, 0.04 and 0.02 mM BB9 was obtained at 14, 10 and 6 min, respectively. In
the same way, 90% discolouration of 0.063, 0.031 and 0.016 mM RB5 was achieved at
90, 60 and 30 min, respectively. Finally, 90% discolouration of 0.14, 0.07 and
0.035 mM AO7 was achieved at 70, 40 and 20 min, respectively. The experimental
results confirmed the effectiveness of electro-assisted Fenton reaction as a
strong oxidizing process in water discolouration and the ability of RVC cathode
to electro-generate and activate H2O2 in situ.
PMID- 26419747
TI - Abstracts of the V International Congress of Histology and Tissue Engineering -
XVII Congress of the Spanish Society of Histology and Tissue Engineering. 12-14
September, 2013, Logrono, Spain.
PMID- 26419748
TI - A novel method for expediting the development of patient-reported outcome
measures and an evaluation of its performance via simulation.
AB - BACKGROUND: Developing valid and reliable patient-reported outcome measures
(PROMs) is a critical step in promoting patient-centered health care, a national
priority in the U.S. Small populations or rare diseases often pose difficulties
in developing PROMs using traditional methods due to small samples. METHODS: To
overcome the small sample size challenge while maintaining psychometric
soundness, we propose an innovative Ordinal Bayesian Instrument Development
(OBID) method that seamlessly integrates expert and participant data in a
Bayesian item response theory (IRT) with a probit link model framework. Prior
distributions obtained from expert data are imposed on the IRT model parameters
and are updated with participants' data. The efficiency of OBID is evaluated by
comparing its performance to classical instrument development performance using
actual and simulation data. RESULTS AND DISCUSSION : The overall performance of
OBID (i.e., more reliable parameter estimates, smaller mean squared errors (MSEs)
and higher predictive validity) is superior to that of classical approaches when
the sample size is small (e.g. less than 100 subjects). Although OBID may exhibit
larger bias, it reduces the MSEs by decreasing variances. Results also closely
align with recommendations in the current literature that six subject experts
will be sufficient for establishing content validity evidence. However, in the
presence of highly biased experts, three experts will be adequate. CONCLUSIONS:
This study successfully demonstrated that the OBID approach is more efficient
than the classical approach when the sample size is small. OBID promises an
efficient and reliable method for researchers and clinicians in future PROMs
development for small populations or rare diseases.
PMID- 26419749
TI - Individual time course of pre- and postsynaptic PET imaging may improve
differential diagnosis of Parkinson's disease and multiple system atrophy: a case
report.
AB - BACKGROUND: Many in vivo studies have shown a difference in pre- and/or
postsynaptic imaging between Parkinson's disease and multiple system atrophy;
however, time course differences in pre- and postsynaptic imaging between
Parkinson's disease and multiple system atrophy have not been rigorously
investigated. CASE PRESENTATION: We report serial positron emission tomography
images of both dopamine transporters and dopamine D2 receptors, obtained from a
Japanese patient with Parkinson's disease who underwent positron emission
tomography scanning at ages 71, 72, 74, and 75 years, and another Japanese
patient with multiple system atrophy who underwent positron emission tomography
scanning at ages 65, 66, and 67 years. Volumes-of-interest were placed on the
striatal subregions. The percentage decreases between the first and last images
showed that dopamine transporter availability decreased with disease progression
in both patients, but that dopamine D2 receptor availability decreased only in
the patient with multiple system atrophy. A partial correlation analysis between
dopamine transporter and dopamine D2 receptor availability, controlling for the
effects of striatal subregional differences, revealed a positive correlation in
the patient with multiple system atrophy (r = 0.893, P = 0.0002), but no
significant correlation in the patient with Parkinson's disease (r = -0.036, P =
0.89). CONCLUSIONS: The time course of pre- and postsynaptic imaging can be
considerably different between Parkinson's disease and multiple system atrophy,
and may be useful in improving the accuracy of discrimination between Parkinson's
disease and multiple system atrophy.
PMID- 26419750
TI - Physicochemical properties affect the synthesis, controlled delivery, degradation
and pharmacokinetics of inorganic nanoporous materials.
AB - Controlling size, shape and uniformity of porous constructs remains a major focus
of the development of porous materials. Over the past two decades, we have seen
significant developments in the fabrication of new, porous-ordered structures
using a wide range of materials, resulting in properties well beyond their
traditional use. Porous materials have been considered appealing, due to
attractive properties such as pore size length, morphology and surface chemistry.
Furthermore, their utilization within the life sciences and medicine has resulted
in significant developments in pharmaceutics and medical diagnosis. This article
focuses on various classes of porous materials, providing an overview of
principle concepts with regard to design and fabrication, surface chemistry and
loading and release kinetics. Furthermore, predictions from a multiscale
mathematical model revealed the role pore length and diameter could have on
payload release kinetics.
PMID- 26419751
TI - Occurrence of diarrhoea and intestinal pathogens in non-medicated nursery pigs.
AB - BACKGROUND: Intestinal disease in nursery pigs is the most common cause of
antibiotic usage in pigs in Denmark. The decision to initiate batch medication of
intestinal diseases in nursery pigs is typically made by the stock personnel
based on clinical assessments of pigs and counting of diarrhoeic faecal pools on
the pen floor. The target population of this study was batches of nursery pigs
(10-66 days after weaning) where the stock personnel assessed the pigs to be
without signs of intestinal disease and therefore did not needed treatment. The
objective was to determine the within-herd prevalence of diarrhoea, and to
determine the prevalence of Escherichia coli F4 and F18, Lawsonia intracellularis
and Brachyspira pilosicoli by quantitative PCR in pigs with and without
diarrhoea. RESULTS: The overall apparent prevalence of diarrhoeic pigs across
sixteen herds was 32.6 % (CI 95 % 27.9-37.3). The prevalence of diarrhoea
increased (p <= 0.001) with age of the pigs (days after weaning) with an odds
ratio of 1.04 (CI 95 % 1.02-1.05) per extra day. Diarrhoeic pools were observed
in 51 % of the pens. L. intracellularis, B. pilosicoli, E. coli F4 and F18 were
detected in 20, 17, 13 and 11 % of the 256 faecal samples analysed by
quantitative PCR respectively. There was no association between detection of
pathogens and diarrhoea status of the individual pigs and between detection of
pathogens in a pen and diarrhoea floor pools. In 51 % of the samples from
diarrhoeic pigs, pathogens were not detected. Only 5 % of the 3060 pigs examined
had clinical signs of diseases other than diarrhoea. CONCLUSIONS: One-third of
non-medicated nursery pigs had diarrhoea when clinically examined even though
they were assessed as healthy by stock personnel. Diarrhoeic status of the pigs
and diarrhoeic pools in pen was a poor indicator of intestinal infections with E.
coli F4 and F18, L. intracellularis and B. pilosicoli and subclinical infections
were common. Therefore, clinical examination and counting of diarrhoea pools
should be supported by microbiological testing as decision tools for initiation
of batch treatments of intestinal infections in nursery pigs.
PMID- 26419752
TI - The influence of neighbourhood green space on children's physical activity and
screen time: findings from the longitudinal study of Australian children.
AB - OBJECTIVE: It is often hypothesised that neighbourhood green space may help
prevent well-known declines in physical activity and increases in sedentary
behaviour that occur across childhood. As most studies in this regard are cross
sectional, the purpose of our study was to use longitudinal data to examine
whether green space promotes active lifestyles as children grow older. METHODS:
Data came from participants (n = 4983; age = 4-5) of the Longitudinal Study of
Australian Children, a nationally representative study on health and child
development. Physical activity and screen time were measured biennially (2004
2012) using questionnaires and time use diaries. Quantity of neighbourhood green
space was objectively measured using Australian Bureau of Statistics mesh block
data for each participant's statistical area level 2. Multilevel regression was
used to test for associations between physical activity and screen time with
green space quantity, adjusting for socio-economic confounders. RESULTS: Boys
living in areas with 10% more neighbourhood green space had a: 7% (95% CI = 1.02,
1.13) greater odds of choosing physically active pastimes; 8% (95 % CI = 0.85,
1.00) lower odds of not enjoying physical activity; 2.3 min reduction in weekend
television viewing (95% CI = -4.00, -0.69); and 7% (95% CI = 1.02; 1.12) and 9%
(95% CI = 1.03; 1.15) greater odds of meeting physical activity guidelines on
weekdays and weekends, respectively. No statistically (or practically)
significant results were observed for girls. CONCLUSION: Current provisions of
neighbourhood green space may be more amenable to promoting active lifestyles
among boys than girls. Research is needed to explore what types of green space
promote active lifestyles in all children.
PMID- 26419753
TI - Highlight: Unpicking the Secrets of the "Great Speciator".
PMID- 26419754
TI - Fluorogenic Thorium Sensors Based on 2,6-Pyridinedicarboxylic Acid-Substituted
Tetraphenylethenes with Aggregation-Induced Emission Characteristics.
AB - A novel fluorescent sensor based on tetraphenylethene (TPE) modified with 2,6
pyridinedicarboxylic acid (PDA) that shows aggregation-induced emission (AIE)
characteristics for thorium recognition with remarkable fluoresence enhancement
response has been synthesized. This sensor is capable of visually distinguishing
Th(4+) among lanthanides, transition metals, and alkali metals under UV light.
Th(4+) can be detected by the naked eye at ppb levels owing to the AIE
phenomenon. The sensor showed high selectivity for Th(4+) compared to all other
metals tested, and this recognition displayed good anti-interference qualities.
This study represents the first application of a AIE fluorescence sensor in
actinide metal recognition and it has potential applications in environmental
systems for thorium ion detection.
PMID- 26419756
TI - Introducing a static receptor to compete with a dynamic combinatorial library in
template binding.
AB - We show herein that establishing a competition between a static receptor and
components of dynamic combinatorial libraries to bind an appropriately selected
template can be used to determine association constants by HPLC analysis after
freezing of the equilibrium.
PMID- 26419760
TI - Enrichment, Distribution of Vanadium-Containing Protein in Vanadium-Enriched Sea
Cucumber Apostichopus japonicus and the Ameliorative Effect on Insulin
Resistance.
AB - Sea cucumbers are a potential source of natural organic vanadium that may improve
insulin resistance. In this work, vanadium was accumulated rapidly in blood, body
wall, and intestine by sea cucumber Apostichopus japonicus. Furthermore, water
soluble vanadium-containing proteins, the main form of the organic vanadium, were
tentatively accumulated and isolated by a bioaccumulation experiment. It was also
designed to evaluate the beneficial effect of vanadium-containing proteins (VCPs)
from sea cucumber rich in vanadium on the development of hyperglycemia and
insulin resistance in C57BL/6J mice fed with a high-fat high-sucrose diet (HFSD).
HFSD mice treated with VCPs significantly decreased fasting blood glucose, serum
insulin, and HOMA-IR values as compared to HFSD mice, respectively. Serum
adiponectin, resistin, TNF-alpha, and leptin levels in insulin-resistant mice
were dramatically reduced by a VCP supplement. These results show an ameliorative
effect on insulin resistance by treatment with VCPs. Such compound seems to be a
valuable therapy to achieve and/or maintain glycemic control and therapeutic
agents in the treatment arsenal for insulin resistance and type 2 diabetes.
PMID- 26419761
TI - Some Elements in Thyroid Tissue are Associated with More Advanced Stage of
Thyroid Cancer in Korean Women.
AB - Excessive exposure to heavy metals including cadmium and lead is known to have
adverse effects on various types of cancer. The aim of the present study was to
evaluate the associations between blood and tissue levels of heavy metals and
trace elements and different stages of thyroid cancer in Korean women. Ninety-two
Korean women undergoing thyroidectomy were included in this study. Blood and
thyroid tissue levels of cadmium, lead, mercury, selenium, and zinc were
measured, and histopathological results, cancer tumor node metastasis (TNM)
stage, and cancer multifocality were assessed. The tissue levels of cadmium,
selenium, and zinc were significantly higher in patients with TNM stages 3 and 4
compared to those in stage 1. The tissue level of cadmium was greater in patients
with higher tumor stage (>=T2) than those with lower stage (T1). Also, the tissue
levels of cadmium and zinc were higher in multifocal group than in unifocal
group. A logistic multiple regression analysis showed that the odds ratio (OR)
for advanced tumor stage group (>=T2) increased in those with higher tissue
cadmium level after adjustment (OR = 1.397, 95 % CI = 1.078-1.811). The
accumulation of cadmium in thyroid tissue may be one of important etiologic
factors for the thyroid cancer progression and aggravation in Korean women.
PMID- 26419762
TI - Plazomicin: an investigational therapy for the treatment of urinary tract
infections.
AB - INTRODUCTION: Living in the ever-expanding era of multidrug-resistant (MDR),
extensively drug-resistant (XDR), and even pandrug-resistant Gram-negative
microorganisms, the medical community is facing the approaching fear of the "End
of Antibiotics." Plazomicin is a next-generation aminoglycoside designed to evade
all clinically relevant aminoglycoside-modifying enzymes, the main mechanism of
aminoglycoside resistance. A newer aminoglycoside active against several MDR-XDR
microorganisms is herein presented and discussed. AREAS COVERED: Herein, the
authors present the currently available information on plazomicin. This includes
the current knowledge concerning plazomicin's: mechanisms of action, in vitro
activity and interactions, its pharmacokinetics, its clinical efficacy in
complicated urinary tract infections (cUTIs) and acute pyelonephritis, and its
toxicity issues. EXPERT OPINION: Plazomicin was developed to evade all clinically
relevant aminoglycoside-modifying enzymes. Unfortunately, ribosomal enzymatic
modification by ribosomal 16S-rRNA methyltransferases confers broad-spectrum high
level aminoglycoside resistance. Still, plazomicin demonstrates high activity
against the Enterobacteriaceae including extended spectrum beta lactamase and
most carbapenemase producers, as well as several of the non-fermenters. When
compared to levofloxacin, the in vivo activity of plazomicin in complicated
urinary tract infections (cUTIs) and in acute pyelonephritis in humans was very
promising. Furthermore, regarding safety, no clinically significant effects on
renal, vestibular, or cochlear function have been observed both at Phase I and II
studies in humans, with mild to moderate adverse events being dose related.
However, the authors believe that the real position of plazomicin in the MDR-XDR
world will be revealed once pending Phase III studies are completed.
PMID- 26419755
TI - Vitamin D deficiency and essential hypertension.
AB - Essential hypertension (EH) results when the balance between vasoconstriction and
vasodilation is shifted in favor of vasoconstriction. This balance is controlled
by the interaction of genetic and epigenetic factors. When there is an unstable
balance, vitamin D deficiency as an epigenetic factor triggers a shift to the
side of vasoconstriction. In this article, we critically analyze clinical
findings on the effect of vitamin D on blood pressure, combined with progress in
molecular mechanisms. We find that vitamin D repletion exerts a clinically
significant antihypertensive effect in vitamin D-deficient EH patients. Of note,
a few trials reported no antihypertensive effect from vitamin D due to suboptimal
study design. Short-term vitamin D supplementation has no effect on blood
pressure in normotensive subjects. This could explain the mixed results and may
provide a theoretical basis for future trials to identify beneficial effects of
vitamin D in intervention for EH.
PMID- 26419763
TI - Osteoarticular infection caused by MDR Pseudomonas aeruginosa: the benefits of
combination therapy with colistin plus beta-lactams.
AB - OBJECTIVES: In the era of emergence of MDR Pseudomonas aeruginosa, osteoarticular
infections (OIs) add more difficulties to its treatment. The role of beta-lactams
(BLs) is questioned and older drugs need to be reconsidered. The objective of
this study was to describe our experience in the management of OIs caused by MDR
P. aeruginosa and evaluate different therapeutic options. METHODS: This was a
retrospective analysis of a prospectively collected cohort (2004-13) of patients
with OI caused by MDR P. aeruginosa. We created two groups: (i) Group A (more
difficult to treat), prosthetic joint infections (PJIs) and osteoarthritis (OA)
managed with device retention; and (ii) Group B (less difficult to treat), OA
managed without device retention. Antibiotic treatment was administered according
to clinician criteria: monotherapy/combined therapy; and BL used by intermittent
bolus (IB)/continuous infusion. RESULTS: Of 34 patients, 15 (44.1%) had PJI and
19 (55.9%) had OA (8 related to an orthopaedic device). Twenty-three cases (68%)
were caused by XDR P. aeruginosa. The initial management included removal of an
orthopaedic device in 14 cases, together with antibiotic [alone, 19 (55.9%; 4
colistin, 14 BL-IB and 1 BL continuous infusion); and in combination, 15 (44.1%;
5 BL-IB and 10 BL continuous infusion)]. The overall cure rate was 50% (39% and
63% in Groups A and B, respectively), ranging from 31.6% with monotherapy to
73.3% with combined therapy (P = 0.016), with special interest within Group A
(cure rate with combined therapy 71.4%, P = 0.049). After rescue therapy, which
included removal of remaining devices, the cure rate reached 85.3%. CONCLUSIONS:
We suggest that the BL/colistin combination is an optimized therapy for OI caused
by MDR P. aeruginosa, together with an appropriate surgical treatment.
PMID- 26419764
TI - Plasticity-related genes in brain development and amygdala-dependent learning.
AB - Learning about motivationally important stimuli involves plasticity in the
amygdala, a temporal lobe structure. Amygdala-dependent learning involves a
growing number of plasticity-related signaling pathways also implicated in brain
development, suggesting that learning-related signaling in juveniles may
simultaneously influence development. Here, we review the pleiotropic functions
in nervous system development and amygdala-dependent learning of a signaling
pathway that includes brain-derived neurotrophic factor (BDNF), extracellular
signaling-related kinases (ERKs) and cyclic AMP-response element binding protein
(CREB). Using these canonical, plasticity-related genes as an example, we discuss
the intersection of learning-related and developmental plasticity in the immature
amygdala, when aversive and appetitive learning may influence the developmental
trajectory of amygdala function. We propose that learning-dependent activation of
BDNF, ERK and CREB signaling in the immature amygdala exaggerates and accelerates
neural development, promoting amygdala excitability and environmental sensitivity
later in life.
PMID- 26419765
TI - Manipulation of combustion waves in carbon-nanotube/fuel composites by highly
reactive Mg nanoparticles.
AB - Manipulating the interface of micro/nanostructured materials and chemical fuels
can change the fundamental characteristics of combustion waves that are generated
during a reaction. In this study, we report that Mg/MgO nanoparticles actively
amplify the propagation of combustion waves at the interface of multi-walled
carbon nanotubes (MWCNTs) and chemical fuels. Fuel/MWCNT and fuel/MWCNT-Mg/MgO
composite films were prepared by a facile synthetic method. We present complete
physiochemical characterization of these composite films and evaluate the
propagating velocities and real-time surface temperatures of combustion waves.
Mg/MgO nanoparticles at the interface enhanced the reaction front velocity by
41%. The resulting explosive reactions supplied additional thermal energy to the
chemical fuel, accelerating flame propagation. Furthermore, the surface
temperatures of the composites with Mg/MgO nanoparticles were much lower,
indicating how the transient heat from the reaction would ignite the unreacted
fuels at lower surface temperatures despite not reaching the necessary activation
energy for a chain reaction. This mechanism contributed to thermopower waves that
amplified the output voltage. Furthermore, large temperature gradients due to the
presence of nanoparticles increased charge transport inside the nanostructured
material, due to the increased thermoelectric effects. This manipulation could
contribute to the active control of interfacially driven combustion waves along
nanostructured materials, yielding many potential applications.
PMID- 26419767
TI - Novel Approach for Developing Dual-Phase Ceramic Membranes for Oxygen Separation
through Beneficial Phase Reaction.
AB - A novel method based on beneficial phase reaction for developing composite
membranes with high oxygen permeation flux and favorable stability was proposed
in this work. Various Ce0.8Sm0.2O2-delta (SDC) + SrCO3+Co3O4 powders with
different SDC contents were successfully fabricated into membranes through high
temperature phase reaction. The X-ray diffraction (XRD) measurements suggest that
the solid-state reaction between the SDC, SrCO3 and Co3O4 oxides occurred at the
temperature for membrane sintering, leading to the formation of a highly
conductive tetragonal perovskite phase SmxSr1-xCoO3-delta. The morphology and
elemental distribution of the dual-phase membranes were characterized using back
scattered scanning electron microscopy and energy dispersive X-ray spectroscopy
(BSEM-EDX). The oxygen bulk diffusivity and surface exchange properties of the
materials were investigated via the electrical conductivity relaxation technique,
which supported the formation of conductive phases. The SDC+20 wt % SrCO3+10.89
wt % Co3O4 membrane exhibited the highest permeation flux among the others,
reaching 0.93 mL cm(-2) min(-1) [STP = standard temperature and pressure] under
an air/helium gradient at 900 degrees C for a membrane with a thickness of 0.5
mm. In addition, the oxygen permeation flux remained stable during the long-time
test. The results demonstrate the beneficial phase reaction as a practical method
for the development of high-performance dual-phase ceramic membranes.
PMID- 26419766
TI - Improvement in Social Competence Using a Randomized Trial of a Theatre
Intervention for Children with Autism Spectrum Disorder.
AB - The efficacy of a peer-mediated, theatre-based intervention on social competence
in participants with autism spectrum disorder (ASD) was tested. Thirty 8-to-14
year-olds with ASD were randomly assigned to the treatment (n = 17) or a wait
list control (n = 13) group. Immediately after treatment, group effects were seen
on social ability, (d = .77), communication symptoms (d = -.86), group play with
toys in the company of peers (d = .77), immediate memory of faces as measured by
neuropsychological (d = .75) and ERP methods (d = .93), delayed memory for faces
(d = .98), and theory of mind (d = .99). At the 2 month follow-up period, group
effects were detected on communication symptoms (d = .82). The results of this
pilot clinical trial provide initial support for the efficacy of the theatre
based intervention.
PMID- 26419768
TI - Safety Profile of Oral Iron Chelator Deferiprone in Chinese Children with
Transfusion-Dependent Thalassaemia.
AB - There is a lack of knowledge regarding the incidence of serious adverse drug
reactions (ADR) to the oral iron chelator deferiprone in Chinese children with
transfusion-dependent thalassaemia. In this retrospective population-based cohort
study, paediatric thalassaemia patients in Hong Kong were screened for serious
and medically important adverse events related to deferiprone therapy using
diagnosis codes, laboratory data and hospital admissions. Potential ADRs were
assessed by reviewing concomitant medications, diagnoses and laboratory data and
evaluated using standardised causality assessment. Eighty-seven patients
contributing 169.8 person-years were included. Thirty ADRs were identified in 21
patients. Most ADRs (56.0%) occurred in the first three months of therapy.
Neutropenia occurred in 11 patients (12.6%; incidence rate 6.5 per 100 patient
years) and severe neutropenia (agranulocytosis) was observed in 5 patients (5.7%,
incidence rate 2.9 per 100 patient-years). Other identified ADRs involve severe
arthropathy, elevated liver enzymes and mild thrombocytopenia. In conclusion, the
safety profile of DFP therapy in Chinese children suffering from transfusion
dependent thalassaemia is in line with previous studies of non-Chinese children.
However, unlike previous studies, we observed a relatively high incidence of
agranulocytosis and neutropenia in patients with simultaneous combined therapy.
Hence close monitoring for white blood cell counts is advised in Chinese children
under combined iron chelation therapy. Further prospective clinical and
pharmacogenetic studies are required to better evaluate this important safety
signal. KEY POINTS: * Half of the identified ADRs related to deferiprone therapy
occurred during the first three months of treatment. * A relatively high
incidence of agranulocytosis and neutropenia. Hence close monitoring for white
blood cell counts is advised in Chinese children under combined iron chelation
therapy.
PMID- 26419769
TI - reSpect: software for identification of high and low abundance ion species in
chimeric tandem mass spectra.
AB - Most shotgun proteomics data analysis workflows are based on the assumption that
each fragment ion spectrum is explained by a single species of peptide ion
isolated by the mass spectrometer; however, in reality mass spectrometers often
isolate more than one peptide ion within the window of isolation that contribute
to additional peptide fragment peaks in many spectra. We present a new tool
called reSpect, implemented in the Trans-Proteomic Pipeline (TPP), which enables
an iterative workflow whereby fragment ion peaks explained by a peptide ion
identified in one round of sequence searching or spectral library search are
attenuated based on the confidence of the identification, and then the altered
spectrum is subjected to further rounds of searching. The reSpect tool is not
implemented as a search engine, but rather as a post-search engine processing
step where only fragment ion intensities are altered. This enables the
application of any search engine combination in the iterations that follow. Thus,
reSpect is compatible with all other protein sequence database search engines as
well as peptide spectral library search engines that are supported by the TPP. We
show that while some datasets are highly amenable to chimeric spectrum
identification and lead to additional peptide identification boosts of over 30%
with as many as four different peptide ions identified per spectrum, datasets
with narrow precursor ion selection only benefit from such processing at the
level of a few percent. We demonstrate a technique that facilitates the
determination of the degree to which a dataset would benefit from chimeric
spectrum analysis. The reSpect tool is free and open source, provided within the
TPP and available at the TPP website. Graphical Abstract ?.
PMID- 26419770
TI - Mapping of Fab-1:VEGF Interface Using Carboxyl Group Footprinting Mass
Spectrometry.
AB - A proof-of-concept study was performed to demonstrate that carboxyl group
footprinting, a relatively simple, bench-top method, has utility for first-pass
analysis to determine epitope regions of therapeutic mAb:antigen complexes. The
binding interface of vascular endothelial growth factor (VEGF) and the Fab
portion of a neutralizing antibody (Fab-1) was analyzed using carboxyl group
footprinting with glycine ethyl ester (GEE) labeling. Tryptic peptides involved
in the binding interface between VEGF and Fab-1 were identified by determining
the specific GEE-labeled residues that exhibited a reduction in the rate of
labeling after complex formation. A significant reduction in the rate of GEE
labeling was observed for E93 in the VEGF tryptic peptide V5, and D28 and E57 in
the Fab-1 tryptic peptides HC2 and HC4, respectively. Results from the carboxyl
group footprinting were compared with the binding interface identified from a
previously characterized crystal structure (PDB: 1BJ1). All of these residues are
located at the Fab-1:VEGF interface according to the crystal structure,
demonstrating the potential utility of carboxyl group footprinting with GEE
labeling for mapping epitopes. Graphical Abstract ?.
PMID- 26419771
TI - 3D ToF-SIMS Analysis of Peptide Incorporation into MALDI Matrix Crystals with Sub
micrometer Resolution.
AB - The analytical sensitivity in matrix-assisted laser desorption/ionization mass
spectrometry (MALDI-MS) is largely affected by the specific analyte-matrix
interaction, in particular by the possible incorporation of the analytes into
crystalline MALDI matrices. Here we used time-of-flight secondary ion mass
spectrometry (ToF-SIMS) to visualize the incorporation of three peptides with
different hydrophobicities, bradykinin, Substance P, and vasopressin, into two
classic MALDI matrices, 2,5-dihydroxybenzoic acid (DHB) and alpha-cyano-4
hydroxycinnamic acid (HCCA). For depth profiling, an Ar cluster ion beam was used
to gradually sputter through the matrix crystals without causing significant
degradation of matrix or biomolecules. A pulsed Bi3 ion cluster beam was used to
image the lateral analyte distribution in the center of the sputter crater. Using
this dual beam technique, the 3D distribution of the analytes and spatial
segregation effects within the matrix crystals were imaged with sub-MUm
resolution. The technique could in the future enable matrix-enhanced (ME)-ToF
SIMS imaging of peptides in tissue slices at ultra-high resolution. Graphical
Abstract ?.
PMID- 26419772
TI - Analysis of Parent/Nitrated Polycyclic Aromatic Hydrocarbons in Particulate
Matter 2.5 Based on Femtosecond Ionization Mass Spectrometry.
AB - Particulate matter 2.5 (PM2.5), collected from ambient air in Fukuoka City, was
analyzed by gas chromatography combined with multiphoton ionization mass
spectrometry using an ultraviolet femtosecond laser (267 nm) as the ionization
source. Numerous parent polycyclic aromatic hydrocarbons (PPAHs) were observed in
a sample extracted from PM2.5, and their concentrations were determined to be in
the range from 30 to 190 pg/m(3) for heavy PPAHs. Standard samples of nitrated
polycyclic aromatic hydrocarbons (NPAHs) were examined, and the limits of
detection were determined to be in the picogram range. The concentration of NPAH
adsorbed on PM2.5 in the air was less than 900-1300 pg/m(3). Graphical Abstract
?.
PMID- 26419773
TI - Reply to Uramoto et al.
PMID- 26419774
TI - Intraoperative ultrasound elastography has little diagnostic benefit for deeper
tumours of the lung.
PMID- 26419775
TI - Food waste volume and origin: Case studies in the Finnish food service sector.
AB - We carried out a project to map the volume and composition of food waste in the
Finnish food service sector. The amount, type and origin of avoidable food waste
were investigated in 51 food service outlets, including schools, day-care
centres, workplace canteens, petrol stations, restaurants and diners. Food
service outlet personnel kept diaries and weighed the food produced and wasted
during a one-week or one-day period. For weighing and sorting, the food waste was
divided into two categories: originally edible (OE) food waste was separated from
originally inedible (OIE) waste, such as vegetable peelings, bones and coffee
grounds. In addition, food waste (OE) was divided into three categories in
accordance with its origins: kitchen waste, service waste and customer leftovers.
According to the results, about 20% of all food handled and prepared in the
sector was wasted. The findings also suggest that the main drivers of wasted food
are buffet services and overproduction.
PMID- 26419776
TI - Mother and adolescent expressed emotion and adolescent internalizing and
externalizing symptom development: a six-year longitudinal study.
AB - In expressed emotion (EE) theory, it is held that high EE household environments
enhance adolescent psychopathological distress. However, no longitudinal study
has been conducted to examine if either the mother's EE or the adolescent's
perception of EE predicts adolescent internalizing and externalizing symptom
dimensions (an EE effect model) or vice versa (psychopathological effect model)
together in one model. To unravel the reciprocal influences of maternal and
adolescent perceived EE to adolescent internalizing and externalizing symptom
dimensions, we tested two (i.e., one for internalizing and one for externalizing)
cross-lagged panel models. In this study, it was found that both internalizing
and externalizing symptom dimensions predicted the adolescent's perception of
maternal EE as well as the mother's own rated EE criticism over time. The
findings of this study should give both researchers and therapists a reason to
reevaluate only using the EE effects model assumption in future EE studies.
PMID- 26419777
TI - Role of macrophages in Wallerian degeneration and axonal regeneration after
peripheral nerve injury.
AB - The peripheral nervous system (PNS) has remarkable regenerative abilities after
injury. Successful PNS regeneration relies on both injured axons and non-neuronal
cells, including Schwann cells and immune cells. Macrophages are the most notable
immune cells that play key roles in PNS injury and repair. Upon peripheral nerve
injury, a large number of macrophages are accumulated at the injury sites, where
they not only contribute to Wallerian degeneration, but also are educated by the
local microenvironment and polarized to an anti-inflammatory phenotype (M2), thus
contributing to axonal regeneration. Significant progress has been made in
understanding how macrophages are educated and polarized in the injured
microenvironment as well as how they contribute to axonal regeneration. Following
the discussion on the main properties of macrophages and their phenotypes, in
this review, we will summarize the current knowledge regarding the mechanisms of
macrophage infiltration after PNS injury. Moreover, we will discuss the recent
findings elucidating how macrophages are polarized to M2 phenotype in the injured
PNS microenvironment, as well as the role and underlying mechanisms of
macrophages in peripheral nerve injury, Wallerian degeneration and regeneration.
Furthermore, we will highlight the potential application by targeting macrophages
in treating peripheral nerve injury and peripheral neuropathies.
PMID- 26419778
TI - Ectopic Expression of WRINKLED1 Affects Fatty Acid Homeostasis in Brachypodium
distachyon Vegetative Tissues.
AB - Triacylglycerol (TAG) is a storage lipid used for food purposes and as a
renewable feedstock for biodiesel production. WRINKLED1 (WRI1) is a transcription
factor that governs fatty acid (FA) synthesis and, indirectly, TAG accumulation
in oil-storing plant tissues, and its ectopic expression has led to TAG
accumulation in vegetative tissues of different dicotyledonous plants. The
ectopic expression of BdWRI1 in the grass Brachypodium distachyon induced the
transcription of predicted genes involved in glycolysis and FA biosynthesis, and
TAG content was increased up to 32.5-fold in 8-week-old leaf blades. However, the
ectopic expression of BdWRI1 also caused cell death in leaves, which has not been
observed previously in dicotyledonous plants such as Arabidopsis (Arabidopsis
thaliana). Lipid analysis indicated that the free FA content was 2-fold elevated
in BdWRI1-expressing leaf blades of B. distachyon. The transcription of predicted
genes involved in beta-oxidation was induced. In addition, linoleic FA treatment
caused cell death in B. distachyon leaf blades, an effect that was reversed by
the addition of the FA biosynthesis inhibitor cerulenin. Taken together, ectopic
expression of BdWRI1 in B. distachyon enhances FA biosynthesis and TAG
accumulation in leaves, as expected, but also leads to increased free FA content,
which has cytotoxic effects leading to cell death. Thus, while WRI appears to
ubiquitously affect FA biosynthesis and TAG accumulation in diverse plants, its
ectopic expression can lead to undesired side effects depending on the context of
the specific lipid metabolism of the respective plant species.
PMID- 26419779
TI - Targeting VEGF-A with a vaccine decreases inflammation and joint destruction in
experimental arthritis.
AB - OBJECTIVES: Inflammation and angiogenesis are two tightly linked processes in
arthritis, and therapeutic targeting of pro-angiogenic factors may contribute to
control joint inflammation and synovitis progression. In this work, we explored
whether vaccination against vascular endothelial growth factor (VEGF) ameliorates
collagen-induced arthritis (CIA). METHODS: Anti-VEGF vaccines were
heterocomplexes consisting of the entire VEGF cytokine (or a VEGF-derived
peptide) linked to the carrier protein keyhole limpet hemocyanin (KLH). Two kinds
of vaccines were separately tested in two independent experiments of CIA. In the
first, we tested a kinoid of the murine cytokine VEGF (VEGF-K), obtained by
conjugating VEGF-A to KLH. For the second, we selected two VEGF-A-derived peptide
sequences to produce heterocomplexes (Vpep1-K and Vpep2-K). DBA/1 mice were
immunized with either VEGF-K, Vpep1-K, or Vpep2-K, before CIA induction. Clinical
and histological scores of arthritis, anti-VEGF, anti-Vpep Ab titers, and anti
VEGF Abs neutralizing capacity were determined. RESULTS: Both VEGF-K and Vpep1-K
significantly ameliorated clinical arthritis scores and reduced synovial
inflammation and joint destruction at histology. VEGF-K significantly reduced
synovial vascularization. None of the vaccines reduced anti-collagen Ab response
in mice. Both VEGF-K and Vpep1-K induced persistently high titers of anti-VEGF
Abs capable of inhibiting VEGF-A bioactivity. CONCLUSION: Vaccination against the
pro-angiogenic factor VEGF-A leads to the production of anti-VEGF polyclonal Abs
and has a significant anti-inflammatory effect in CIA. Restraining Ab response to
a single peptide sequence (Vpep1) with a peptide vaccine effectively protects
immunized mice from joint inflammation and destruction.
PMID- 26419780
TI - Illness intrusiveness and subjective well-being in patients with glioblastoma.
AB - Glioblastoma (GBM) is the most common adult CNS malignancy but its impact on
quality of life (QOL) is poorly understood. In other patient populations, illness
intrusiveness (the extent to which disease and treatment disrupts valued
activities and interests) is associated with low subjective well-being, after
controlling for disease and treatment variables. In this cross-sectional cohort
study, we examined the relations among illness intrusiveness, disease burden, and
subjective well-being in GBM. 73 GBM patients completed validated self-report
measures of depression, positive affect, illness intrusiveness, and health
related QOL. Responses were compared to data from six other cancer groups using
repeated measures analyses of variance. Hierarchical multiple-regression analyses
tested the hypothesis that illness intrusiveness accounts for well-being after
controlling for the effects of disease burden. GBM patients reported less
positive affect, more depression, and more illness intrusiveness than people with
other cancers. Illness intrusiveness correlated with depression and (low)
positive affect. Associations among cancer symptoms, depression, and positive
affect decreased when illness intrusiveness was added to regression equations.
Good performance status and high cancer-symptom burden were associated with
illness intrusiveness and depression. GBM patients report greater distress, lower
positive affect, and more illness intrusiveness than people with other cancers.
Subjective well-being is mediated in part by illness intrusiveness in this
population. In addition to medical treatment, efforts to help patients remain
engaged in valued activities and interests may help preserve QOL after the
diagnosis of a GBM.
PMID- 26419781
TI - Erratum to: Survival prediction in high-grade gliomas using CT perfusion imaging.
PMID- 26419782
TI - 3D RuO2 Microsupercapacitors with Remarkable Areal Energy.
AB - Large areal capacitance electrodes made of ruthenium oxide on highly porous gold
current collectors are realized by an attractive approach. The hybrid structure
exhibits a capacitance in excess of 3 F cm(-2) and an areal energy density for
all-solid-state microsupercapacitors that is comparable to those of
microbatteries.
PMID- 26419783
TI - The developmental inter-relationships between activity, novelty preferences, and
delay discounting in male and female rats.
AB - Increased locomotion, novelty-seeking, and impulsivity are risk factors
associated with substance use. In this study, the inter-relationships between
activity, novelty preferences, and delay discounting, a measure of impulsivity,
were examined across three stages: juvenile/early adolescence (postnatal Day [P]
15, 19, and 42 for activity, novelty, and impulsivity, respectively),
adolescent/late adolescent (P28, 32, 73), and adult (P90, 94, 137) in male and
female rats. Our estimates of impulsive choice, where animals were trained to
criterion, revealed an age * sex interaction where early adolescent females had
the lowest levels of impulsivity. The relationships of activity and novelty to
impulsivity significantly changed across age within each sex. Early adolescent
males with high activity, but low novelty preferences, were more impulsive;
however, low activity and high novelty preferences were related to high
impulsivity in adult males. Female activity gradually increased across age, but
did not show a strong relationship with impulsivity. Novelty preferences are
moderately related to impulsivity into adulthood in females. These data show that
males and females have different developmental trajectories for these behaviors.
Males show greater sensation-seeking (e.g., activity) and risky behavior (e.g.,
novelty preferences) earlier in life, whereas these behaviors emerge during
adolescence in females.
PMID- 26419784
TI - A thoracodorsal artery perforator chimeric free flap for prevention of
microvascular pedicle compression in lower extremity reconstruction.
AB - BACKGROUND: Chimeric flaps are often used in reconstructive fields for multiple
defects, different functional defects, and extensive defects. In this article, we
present the results of the use of thoracodorsal artery perforator (TDAp) chimeric
flaps including a latissimus dorsi (LD) or serratus anterior (SA) muscle to
prevent pedicle compression for lower extremity reconstruction. METHODS: Nineteen
TDAp chimeric flaps were used to prevent pedicle compression. Seven were female
and 12 male. Patients' age ranged from 32 to 73 years. After harvesting TDAp skin
flap, LD or SA muscle could be harvested along with the thoracodorsal vessels.
Skin flap was incorporated into the main defect and muscle cuffs were positioned
along the vascular pedicle. RESULTS: In 11 cases, there were two components, a
skin flap and a muscle flap, and the other 8 were three components, a skin flap
and two muscle flaps. The dimensions of the skin flaps ranged from 8 * 5 to 18 *
10 cm, and the muscle flaps ranged from 3 * 2 cm to 8 * 6 cm. The recipient
vessel was anterior tibial artery or dorsalis pedis artery. All flap survived.
Five cases suffered minor complications including donor site wound disruption,
skin flap wound disruption, partial loss of the skin flap, and partial loss of
the SA muscle flap. The mean follow-up was 13.9 months. All the patients were
able to wear shoes without debulking procedures. CONCLUSION: The TDAp chimeric
flaps including LD or SA muscle flaps were useful for covering the vascular
pedicle and relieved vascular compression during lower extremity reconstruction.
(c) 2015 Wiley Periodicals, Inc. Microsurgery, 38:46-50, 2018..
PMID- 26419787
TI - Nutritional status, tooth wear and quality of life in Brazilian schoolchildren.
AB - OBJECTIVE: To evaluate the correlation among nutritional status, tooth wear and
quality of life in Brazilian schoolchildren. DESIGN: The study followed a cross
sectional design. Nutritional status was measured via anthropometry using BMI and
tooth wear was measured using the Dental Wear Index; both these assessments were
carried out by a trained recorder according to standard criteria. A modified
version of the Child Oral Impacts on Daily Performances was used to assess
quality of life. SETTING: City of Bauru, in Brazil. SUBJECTS: A cluster sample of
396 schoolchildren (194 boys and 202 girls) aged 7-10 years. RESULTS: The
anthropometric assessment showed similar situations for both sexes regarding
underweight (31.40 % in boys and 30.20 % in girls) and overweight/obesity (33.96
% in boys and 33.17 % in girls). The underweight children showed a greater
severity of tooth wear in the primary teeth (OR=0.72; CI 0.36, 1.42), although in
the permanent dentition the obese children had a greater severity of tooth wear
(OR=1.42; 95 % CI 0.31, 6.55). The tooth wear was correlated with age for both
dentitions. CONCLUSIONS: Tooth wear in the primary and permanent dentition may be
related to nutritional status. Tooth wear and obesity did not have a significant
impact on the schoolchildren's perception of quality of life.
PMID- 26419788
TI - Changing nomenclature for PBC: From 'cirrhosis' to 'cholangitis'.
PMID- 26419785
TI - Purification and characterization of tenerplasminin-1, a serine peptidase
inhibitor with antiplasmin activity from the coral snake (Micrurus tener tener)
venom.
AB - A plasmin inhibitor, named tenerplasminin-1 (TP1), was isolated from Micrurus
tener tener (Mtt) venom. It showed a molecular mass of 6542Da, similarly to
Kunitz-type serine peptidase inhibitors. The amidolytic activity of plasmin
(0.5nM) on synthetic substrate S-2251 was inhibited by 91% following the
incubation with TP1 (1nM). Aprotinin (2nM) used as the positive control of
inhibition, reduced the plasmin amidolytic activity by 71%. Plasmin fibrinolytic
activity (0.05nM) was inhibited by 67% following incubation with TP1 (0.1nM). The
degradation of fibrinogen chains induced by plasmin, trypsin or elastase was
inhibited by TP1 at a 1:2, 1:4 and 1:20 enzyme:inhibitor ratio, respectively. On
the other hand, the proteolytic activity of crude Mtt venom on fibrinogen chains,
previously attributed to metallopeptidases, was not abolished by TP1. The tPA
clot lysis assay showed that TP1 (0.2nM) acts like aprotinin (0.4nM) inducing a
delay in lysis time and lysis rate which may be associated with the inhibition of
plasmin generated from the endogenous plasminogen activation. TP1 is the first
serine protease plasmin-like inhibitor isolated from Mtt snake venom which has
been characterized in relation to its mechanism of action, formation of a
plasmin:TP1 complex and therapeutic potential as anti-fibrinolytic agent, a
biological characteristic of great interest in the field of biomedical research.
They could be used to regulate the fibrinolytic system in pathologies such as
metastatic cancer, parasitic infections, hemophilia and other hemorrhagic
syndromes, in which an intense fibrinolytic activity is observed.
PMID- 26419789
TI - Dr Ninan T Mathew--A tribute (1937-2015).
PMID- 26419786
TI - Gold(I)-Catalyzed Enantioselective Desymmetrization of 1,3-Diols through
Intramolecular Hydroalkoxylation of Allenes.
AB - A gold(I)-catalyzed enantioselective desymmetrization of 1,3-diols was achieved
by intramolecular hydroalkoxylation of allenes. The catalyst system 3-F
dppe(AuCl)2/(R)-C8-TRIPAg proved to be specifically efficient to promote the
desymmetrizing cyclization of 2-aryl-1,3-diols, which have proven challenging
substrates in previous reports. Multisubstituted tetrahydrofurans were prepared
in good yield with good enantioselectivity and diastereoselectivity by this
method.
PMID- 26419790
TI - Do interictal microembolic signals play a role in higher cortical dysfunction
during migraine aura?
AB - INTRODUCTION: The aim of this study was to evaluate the prevalence and clinical
impact of interictal microembolic signals (MES) in patients suffering from
migraine with higher cortical dysfunction (HCD), such as language and memory
impairment, during an aura. PATIENTS AND METHODS: This study was carried out on
34 migraineurs with language and memory impairment during aura (HCD group), 31
migraineurs with only visual or visual and somatosensory symptoms during aura
(Control group I), and 34 healthy controls (Control group II). We used a Doppler
instrument to detect microemboli. Demographic data, disease features and the
detection of MES between these groups, as well as the predictors of HCD during
the aura, were analyzed. RESULTS: The duration of aura was longer and the
frequency of aura was higher among patients with language and memory impairment
during aura compared to Control group I. MES was detected in 29.4% patients from
the HCD group, which was significantly higher compared to 3.2% in Control group I
and 5.9% in Control group II. Regarding the absence or presence of MES,
demographic and aura features were not different in the HCD subgroups. A longer
duration of aura, the presence of somatosensory symptoms during the aura and the
presence of interictal MES were independent predictors of HCD during the aura.
CONCLUSION: The present findings indicate that HCD and MES are related in
patients with migraine with aura. Further research is needed to better understand
the exact pathophysiological mechanism.
PMID- 26419791
TI - Treatment of older people with dementia in surgical wards from the viewpoints of
the patients and close relatives.
AB - AIMS AND OBJECTIVES: The aim of this study was to describe the treatment of older
people with dementia in surgical wards from the viewpoints of the patients and
their close relatives. BACKGROUND: Little is known about the impact of the
increasing number of older people with dementia on the treatment of patients in
acute care. DESIGN: A qualitative, descriptive design was used. METHOD: The data
were collected using unstructured interviews, which were then subjected to
inductive content analysis. RESULTS: Support from close relatives was significant
for the mental and social wellbeing of older dementia patients during their
hospital stay. People with dementia felt insecure in their relatives' absence,
and missed them. For the relatives, the patients' hospital stay was emotionally
heavy. The relatives desired more emotional support from the nursing staff. The
participating patients hoped that the nursing staff would spend more time
discussing their cases with them. One of the factors that hindered good care of
an older person with dementia was use of restraint. Relatives felt that use of
restraints violated patients' dignity. CONCLUSIONS: To improve the treatment of
the people with dementia, the close relatives need to participate in planning the
nature of care for the patients. RELEVANCE TO CLINICAL PRACTICE: The results are
applicable for efforts to improve the abilities of nursing staff, physicians and
close relatives in the treatment of older people with dementia in acute care
settings.
PMID- 26419792
TI - DAMP production by human islets under low oxygen and nutrients in the presence or
absence of an immunoisolating-capsule and necrostatin-1.
AB - In between the period of transplantation and revascularization, pancreatic islets
are exposed to low-oxygen and low-nutrient conditions. In the present study we
mimicked those conditions in vitro to study the involvement of different cell
death processes, release of danger-associated molecular patterns (DAMP), and
associated in vitro immune activation. Under low-oxygen and low-nutrient
conditions, apoptosis, autophagy and necroptosis occur in human islets.
Necroptosis is responsible for DAMP-release such as dsDNA, uric acid, and HMGB1.
The sensors of the innate immune system able to recognize these DAMPs are mainly
TLR, NOD receptors, and C-type lectins. By using cell-lines with a non-functional
adaptor molecule MyD88, we were able to show that the islet-derived DAMPs signal
mainly via TLR. Immunoisolation in immunoprotective membranes reduced DAMP
release and immune activation via retention of the relative large DAMPs in the
capsules. Another effective strategy was suppressing necroptosis using the
inhibitor nec-1. Although the effect on cell-survival was minor, nec-1 was able
to reduce the release of HMGB1 and its associated immune activation. Our data
demonstrate that in the immediate post-transplant period islets release DAMPs
that in vitro enhance responses of innate immune cells. DAMP release can be
reduced in vitro by immunoisolation or intervention with nec-1.
PMID- 26419793
TI - Effects of ethanol, molasses and Lactobacillus plantarum on the fermentation
quality, in vitro digestibility and aerobic stability of total mixed ration
silages in the Tibetan plateau of China.
AB - In Tibet, it is common practice to make and relocate total mixed ration (TMR)
silages before feeding due to the uneven distribution of forages temporally and
spatially. This study was conducted to investigate the effects of Lactobacillus
plantarum (L), molasses (M) or ethanol (E) on the fermentation quality and
aerobic stability of local adaptive TMR silage. After 45 days of ensiling, pH and
ammonia nitrogen in inoculated TMR silages were significantly lower than control.
During the first 6 days of the aerobic exposure test, a small fluctuation in
lactic acid concentration for all TMR silages was observed, and then silages with
ethanol continued this trend, while lactic acid in silage without ethanol sharply
decreased until the end of the aerobic exposure period. Meanwhile, pH gradually
increased along the aerobic exposure; silages treated with ethanol showed lower
pH after 9 days of aerobic exposure. The population of yeast gradually increased
during 6 days of aerobic exposure, after that an accelerated rise was observed in
TMR silages without ethanol. The combinational beneficial effect of L. plantarum
and ethanol was found in combined addition of ethanol and Lactobacillus plantarum
silages (EL), indicated by intermediate fermentation quality and higher aerobic
stability.
PMID- 26419795
TI - Yoga for Self-Care and Burnout Prevention Among Nurses.
AB - The promotion of self-care and the prevention of burnout among nurses is a public
health priority. Evidence supports the efficacy of yoga to improve physical and
mental health outcomes, but few studies have examined the influence of yoga on
nurse-specific outcomes. The purpose of this pilot-level randomized controlled
trial was to examine the efficacy of yoga to improve self-care and reduce burnout
among nurses. Compared with controls (n = 20), yoga participants (n = 20)
reported significantly higher self-care as well as less emotional exhaustion and
depersonalization upon completion of an 8-week yoga intervention. Although the
control group demonstrated no change throughout the course of the study, the yoga
group showed a significant improvement in scores from pre- to post-intervention
for self-care (p < .001), mindfulness (p = .028), emotional exhaustion (p =
.008), and depersonalization (p = .007) outcomes. Implications for practice are
discussed.
PMID- 26419797
TI - Global Tuberculosis.
AB - Tuberculosis (TB) infections remain a common but deadly disease. TB control in
health care and correctional settings presents numerous public health challenges
for occupational and correctional health nurses.
PMID- 26419798
TI - The visual perception of natural motion: abnormal task-related neural activity in
DYT1 dystonia.
AB - Although primary dystonia is defined by its characteristic motor manifestations,
non-motor signs and symptoms have increasingly been recognized in this disorder.
Recent neuroimaging studies have related the motor features of primary dystonia
to connectivity changes in cerebello-thalamo-cortical pathways. It is not known,
however, whether the non-motor manifestations of the disorder are associated with
similar circuit abnormalities. To explore this possibility, we used functional
magnetic resonance imaging to study primary dystonia and healthy volunteer
subjects while they performed a motion perception task in which elliptical target
trajectories were visually tracked on a computer screen. Prior functional
magnetic resonance imaging studies of healthy subjects performing this task have
revealed selective activation of motor regions during the perception of 'natural'
versus 'unnatural' motion (defined respectively as trajectories with kinematic
properties that either comply with or violate the two-thirds power law of
motion). Several regions with significant connectivity changes in primary
dystonia were situated in proximity to normal motion perception pathways,
suggesting that abnormalities of these circuits may also be present in this
disorder. To determine whether activation responses to natural versus unnatural
motion in primary dystonia differ from normal, we used functional magnetic
resonance imaging to study 10 DYT1 dystonia and 10 healthy control subjects at
rest and during the perception of 'natural' and 'unnatural' motion. Both groups
exhibited significant activation changes across perceptual conditions in the
cerebellum, pons, and subthalamic nucleus. The two groups differed, however, in
their responses to 'natural' versus 'unnatural' motion in these regions. In
healthy subjects, regional activation was greater during the perception of
natural (versus unnatural) motion (P < 0.05). By contrast, in DYT1 dystonia
subjects, activation was relatively greater during the perception of unnatural
(versus natural) motion (P < 0.01). To explore the microstructural basis for
these functional changes, the regions with significant interaction effects (i.e.
those with group differences in activation across perceptual conditions) were
used as seeds for tractographic analysis of diffusion tensor imaging scans
acquired in the same subjects. Fibre pathways specifically connecting each of the
significant functional magnetic resonance imaging clusters to the cerebellum were
reconstructed. Of the various reconstructed pathways that were analysed, the
ponto-cerebellar projection alone differed between groups, with reduced fibre
integrity in dystonia (P < 0.001). In aggregate, the findings suggest that the
normal pattern of brain activation in response to motion perception is disrupted
in DYT1 dystonia. Thus, it is unlikely that the circuit changes that underlie
this disorder are limited to primary sensorimotor pathways.
PMID- 26419800
TI - Chris Marshall 1949-2015.
PMID- 26419799
TI - Regional brain hypometabolism is unrelated to regional amyloid plaque burden.
AB - In its original form, the amyloid cascade hypothesis of Alzheimer's disease holds
that fibrillar deposits of amyloid are an early, driving force in pathological
events leading ultimately to neuronal death. Early clinicopathological
investigations highlighted a number of inconsistencies leading to an updated
hypothesis in which amyloid plaques give way to amyloid oligomers as the driving
force in pathogenesis. Rather than focusing on the inconsistencies, amyloid
imaging studies have tended to highlight the overlap between regions that show
early amyloid plaque signal on positron emission tomography and that also happen
to be affected early in Alzheimer's disease. Recent imaging studies investigating
the regional dependency between metabolism and amyloid plaque deposition have
arrived at conflicting results, with some showing regional associations and other
not. We extracted multimodal neuroimaging data from the Alzheimer's disease
neuroimaging database for 227 healthy controls and 434 subjects with mild
cognitive impairment. We analysed regional patterns of amyloid deposition,
regional glucose metabolism and regional atrophy using florbetapir ((18)F)
positron emission tomography, (18)F-fluordeoxyglucose positron emission
tomography and T1-weighted magnetic resonance imaging, respectively.
Specifically, we derived grey matter density and standardized uptake value ratios
for both positron emission tomography tracers in 404 functionally defined regions
of interest. We examined the relation between regional glucose metabolism and
amyloid plaques using linear models. For each region of interest, correcting for
regional grey matter density, age, education and disease status, we tested the
association of regional glucose metabolism with (i) cortex-wide florbetapir
uptake; (ii) regional (i.e. in the same region of interest) florbetapir uptake;
and (iii) regional florbetapir uptake while correcting in addition for cortex
wide florbetapir uptake. P-values for each setting were Bonferroni corrected for
404 tests. Regions showing significant hypometabolism with increasing cortex-wide
amyloid burden were classic Alzheimer's disease-related regions: the medial and
lateral parietal cortices. The associations between regional amyloid burden and
regional metabolism were more heterogeneous: there were significant hypometabolic
effects in posterior cingulate, precuneus, and parietal regions but also
significant positive associations in bilateral hippocampus and entorhinal cortex.
However, after correcting for global amyloid burden, few of the negative
associations remained and the number of positive associations increased. Given
the wide-spread distribution of amyloid plaques, if the canonical cascade
hypothesis were true, we would expect wide-spread, cortical hypometabolism.
Instead, cortical hypometabolism appears to be linked to global amyloid burden.
Thus we conclude that regional fibrillar amyloid deposition has little to no
association with regional hypometabolism.
PMID- 26419801
TI - Translating the effects of mTOR on secretory senescence.
AB - Cellular senescence is often accompanied by the production of secreted proteins
that mediate the diverse effects of senescence on the tissue microenvironment.
The mammalian target of rapamycin (mTOR), a master regulator of protein
synthesis, is now shown to control the senescence-associated secretory phenotype
by modulating gene transcription and mRNA translation and stabilization.
PMID- 26419802
TI - STIMATE reveals a STIM1 transitional state.
AB - Decreases in endoplasmic reticulum calcium content are sensed by resident STIM
proteins, which can activate plasma membrane Orai channels to facilitate Ca(2+)
entry. The role of STIMATE, a previously unknown component of the store-operated
calcium entry complex, has now been identified and defined.
PMID- 26419803
TI - Corrigendum: Combined CSL and p53 downregulation promotes cancer-associated
fibroblast activation.
PMID- 26419804
TI - Erratum: mTOR regulates MAPKAPK2 translation to control the senescence-associated
secretory phenotype.
PMID- 26419805
TI - A tunable azine covalent organic framework platform for visible light-induced
hydrogen generation.
AB - Hydrogen evolution from photocatalytic reduction of water holds promise as a
sustainable source of carbon-free energy. Covalent organic frameworks (COFs)
present an interesting new class of photoactive materials, which combine three
key features relevant to the photocatalytic process, namely crystallinity,
porosity and tunability. Here we synthesize a series of water- and photostable 2D
azine-linked COFs from hydrazine and triphenylarene aldehydes with varying number
of nitrogen atoms. The electronic and steric variations in the precursors are
transferred to the resulting frameworks, thus leading to a progressively enhanced
light-induced hydrogen evolution with increasing nitrogen content in the
frameworks. Our results demonstrate that by the rational design of COFs on a
molecular level, it is possible to precisely adjust their structural and
optoelectronic properties, thus resulting in enhanced photocatalytic activities.
This is expected to spur further interest in these photofunctional frameworks
where rational supramolecular engineering may lead to new material applications.
PMID- 26419806
TI - Electrocatalytic O2-Reduction by Synthetic Cytochrome c Oxidase Mimics:
Identification of a "Bridging Peroxo" Intermediate Involved in Facile 4e(-)/4H(+)
O2-Reduction.
AB - A synthetic heme-Cu CcO model complex shows selective and highly efficient
electrocatalytic 4e(-)/4H(+) O2-reduction to H2O with a large catalytic rate
(>10(5) M(-1) s(-1)). While the heme-Cu model (FeCu) shows almost exclusive 4e(
)/4H(+) reduction of O2 to H2O (detected using ring disk electrochemistry and
rotating ring disk electrochemistry), when imidazole is bound to the heme
(Fe(Im)Cu), this same selective O2-reduction to water occurs only under slow
electron fluxes. Surface enhanced resonance Raman spectroscopy coupled to dynamic
electrochemistry data suggests the formation of a bridging peroxide intermediate
during O2-reduction by both complexes under steady state reaction conditions,
indicating that O-O bond heterolysis is likely to be the rate-determining step
(RDS) at the mass transfer limited region. The O-O vibrational frequencies at 819
cm(-1) in (16)O2 (759 cm(-1) in (18)O2) for the FeCu complex and at 847 cm(-1)
(786 cm(-1)) for the Fe(Im)Cu complex, indicate the formation of side-on and end
on bridging Fe-peroxo-Cu intermediates, respectively, during O2-reduction in an
aqueous environment. These data suggest that side-on bridging peroxide
intermediates are involved in fast and selective O2-reduction in these synthetic
complexes. The greater amount of H2O2 production by the imidazole bound complex
under fast electron transfer is due to 1e(-)/1H(+) O2-reduction by the distal Cu
where O2 binding to the water bound low spin Fe(II) complex is inhibited.
PMID- 26419809
TI - Diversity of fig glands is associated with nursery mutualism in fig trees.
AB - PREMISE OF THE STUDY: Fig trees (Moraceae) have remarkable enclosed
inflorescences called figs or syconia. The flowers are pollinated by host
specific fig wasps that enter the fig to lay their eggs. This nursery pollination
system is one of the most studied of tropical mutualism interactions, but the
source of the volatiles that attract fig wasps to their specific host figs has
not been confirmed. The fragrance is the basis of host selection and, therefore,
of reproductive isolation among sympatric Ficus species. This study locates and
characterizes the glands likely to be responsible for pollinator attraction and
also protection from herbivory in the figs of nine Ficus species representing all
the major lineages within the genus. METHODS: Figs with receptive pistillate
flowers were examined using light and scanning electron microscopy. Tests for
histolocalization of substances were employed to detect glandular activity
throughout the figs. KEY RESULTS: A great diversity of glands is found throughout
the fig, and for the first time, the sites producing fragrances are identified.
Scent glands are present on the ostiolar bracts and the outer layers of the fig
receptacle. Laticifers and phenolic-producing idioblasts, epidermis, and
trichomes associated with fig protection occur on the ostiolar bracts, the fig
receptacle, and floral tissues. CONCLUSIONS: The volatiles produced by glands on
the ostiolar bracts are candidate sources for the long-distance attraction of
pollinator fig wasps. Scent glands on the outer layers of the receptacle may also
play a role in chemical perception of the figs or may be related to their
protection. The high cost to the plants if the figs are eaten and the temperature
conditions required for nursery pollination are likely the factors that led to
the selection of phenolic glands and laticifers during the group's evolution.
PMID- 26419807
TI - Interactions between chronic ethanol consumption and thiamine deficiency on
neural plasticity, spatial memory, and cognitive flexibility.
AB - BACKGROUND: Many alcoholics display moderate to severe cognitive dysfunction
accompanied by brain pathology. A factor confounded with prolonged heavy alcohol
consumption is poor nutrition, and many alcoholics are thiamine deficient. Thus,
thiamine deficiency (TD) has emerged as a key factor underlying alcohol-related
brain damage (ARBD). TD in humans can lead to Wernicke Encephalitis that can
progress into Wernicke-Korsakoff syndrome and these disorders have a high
prevalence among alcoholics. Animal models are critical for determining the exact
contributions of ethanol (EtOH)- and TD-induced neurotoxicity, as well as the
interactions of those factors to brain and cognitive dysfunction. METHODS: Adult
rats were randomly assigned to 1 of 6 treatment conditions: chronic EtOH
treatment (CET) where rats consumed a 20% v/v solution of EtOH over 6 months;
severe pyrithiamine-induced TD (PTD-moderate acute stage); moderate PTD (PTD
early acute stage); moderate PTD followed by CET (PTD-CET); moderate PTD during
CET (CET-PTD); and pair-fed (PF) control. After recovery from treatment, all rats
were tested on spontaneous alternation and attentional set-shifting. After
behavioral testing, brains were harvested for determination of mature brain
derived neurotrophic factor (BDNF) and thalamic pathology. RESULTS: Moderate TD
combined with CET, regardless of treatment order, produced significant
impairments in spatial memory, cognitive flexibility, and reductions in brain
plasticity as measured by BDNF levels in the frontal cortex and hippocampus.
These alterations are greater than those seen in moderate TD alone, and the
synergistic effects of moderate TD with CET lead to a unique cognitive profile.
However, CET did not exacerbate thalamic pathology seen after moderate TD.
CONCLUSIONS: These data support the emerging theory that subclinical TD during
chronic heavy alcohol consumption is critical for the development of significant
cognitive impairment associated with ARBD.
PMID- 26419808
TI - Ikaros mediates the DNA methylation-independent silencing of MCJ/DNAJC15 gene
expression in macrophages.
AB - MCJ (DNAJC15) is a mitochondrial protein that regulates the mitochondrial
metabolic status of macrophages and their response to inflammatory stimuli. CpG
island methylation in cancer cells constitutes the only mechanism identified for
the regulation of MCJ gene expression. However, whether DNA methylation or
transcriptional regulation mechanisms are involved in the physiological control
of this gene expression in non-tumor cells remains unknown. We now demonstrate a
mechanism of regulation of MCJ expression that is independent of DNA methylation.
IFNgamma, a protective cytokine against cardiac inflammation during Lyme
borreliosis, represses MCJ transcription in macrophages. The transcriptional
regulator, Ikaros, binds to the MCJ promoter in a Casein kinase II-dependent
manner, and mediates the repression of MCJ expression. These results identify the
MCJ gene as a transcriptional target of IFNgamma and provide evidence of the
dynamic adaptation of normal tissues to changes in the environment as a way to
adapt metabolically to new conditions.
PMID- 26419810
TI - Pollen structure and development in Nymphaeales: insights into character
evolution in an ancient angiosperm lineage.
AB - PREMISE OF THE STUDY: A knowledge of pollen characters in early-diverging
angiosperm lineages is essential for understanding pollen evolution and the role
of pollen in angiosperm diversification. In this paper, we report and synthesize
data on mature pollen and pollen ontogeny from all genera of Nymphaeales within a
comparative, phylogenetic context and consider pollen evolution in this early
diverging angiosperm lineage. We describe mature pollen characters for Euryale,
Barclaya, and Nymphaea ondinea, taxa for which little to no structural data
exist. METHODS: We studied mature pollen for all nymphaealean genera using light,
scanning electron, and transmission electron microscopy. We reviewed published
reports of nymphaealean pollen to provide a comprehensive discussion of pollen
characters in water lilies. KEY RESULTS: Nymphaeales exhibit diversity in key
pollen characters, including dispersal unit size, ornamentation, aperture
morphology, and tapetum type. All Nymphaeales pollen are tectate-columellate,
exhibiting one of two distinct patterns of infratectal ultrastructure-a thick
infratectal space with robust columellae or a thin infratectal space with thin
columellae. All genera have pollen with a lamellate endexine that becomes
compressed in the proximal, but not distal wall. This endexine ultrastructure
supports the operculate hypothesis for aperture origin. Nymphaeaceae pollen
exhibit a membranous granular layer, which is a synapomorphy of the family.
CONCLUSIONS: Variation in pollen characters indicates that significant potential
for lability in pollen development was present in Nymphaeales at the time of its
divergence from the rest of angiosperms. Structural and ontogenetic data are
essential for interpreting pollen characters, such as infratectum and endexine
ultrastructure in Nymphaeales.
PMID- 26419811
TI - Floral anatomy and vegetative development in Ceratophyllum demersum: a
morphological picture of an "unsolved" plant.
AB - PREMISE OF THE STUDY: The phylogenetic position of Ceratophyllum is still
controversial in recent molecular analyses of angiosperms, with various
suggestions of a sister group relation to all other angiosperms, eudicots,
monocots, eudicots + monocots, and magnoliids. Therefore, the morphological
characters of Ceratophyllum are important for resolving the phylogeny of
angiosperms. In this study, we observed the detailed developmental anatomy of all
lateral organs and their configurations to elucidate the floral development and
phyllotactic pattern of Ceratophyllum demersum. METHODS: We observed fixed shoots
of C. demersum with scanning electron microscopy and serial sections of the
samples with light microscopy. KEY RESULTS: Bract primordia arise first, followed
by the stamen primordia in staminate flowers. Both bracts and stamens initiate
unidirectionally, first on the abaxial side of the floral apex and later on the
adaxial side, most likely due to the contact pressure imposed by the leaf
primordium at the superior node. In pistillate flowers, bract primordia on the
abaxial side were also initiated first. The configuration of buds at one node
showed six patterns and each pattern included at least one vegetative bud, and
flower buds were always accompanied by vegetative buds at the same node.
CONCLUSIONS: The initiation pattern of organs in the outer whorls of C. demersum
flowers is distorted by mechanical pressure, resulting in the phyllotactic
variation of staminate flowers. Vegetative buds are the main axillary buds with
floral buds as accessory buds, which suggests that the shoot of C. demersum has
been modified from a decussate phyllotaxis.
PMID- 26419813
TI - Think Stoma Nurse: a tool to trigger referral to specialist care.
AB - This article describes the initial development and subsequent evolution of a
simple referral assessment tool for stoma care. The first author's personal
experience identified that there was widespread inconsistency in perceptions of
local multidisciplinary teams as to when it was appropriate to refer to specific
specialist nursing teams. This resulted in both inappropriate and delayed
referrals. A 'Think Specialist Nurse' initiative was developed across the
author's trust, building on the traffic light template from the 'ThinkGlucose'
tool, to facilitate referrals to clinical nurse specialists. The stoma-care
specific tool, 'Think Stoma Nurse', has subsequently evolved beyond its initial
audience, and has been adapted into materials aimed at patients and carers.
PMID- 26419814
TI - Stoma Care Nurse of the Year: BJN AWARD RUNNER UP.
AB - Gill Little, National Nurse Manager SecuriCare (Medical), entered Helen, Lyn,
Tara and Gillian into the Stoma Care Nurse of the Year category. Here, she
explains the reasons behind her nomination.
PMID- 26419812
TI - Infants born large-for-gestational-age display slower growth in early infancy,
but no epigenetic changes at birth.
AB - We evaluated the growth patterns of infants born large-for-gestational-age (LGA)
from birth to age 1 year compared to those born appropriate-for-gestational-age
(AGA). In addition, we investigated possible epigenetic changes associated with
being born LGA. Seventy-one newborns were classified by birth weight as AGA
(10(th)-90(th) percentile; n = 42) or LGA (>90(th) percentile; n = 29). Post
natal follow-up until age 1 year was performed with clinical assessments at 3, 6,
and 12 months. Genome-wide DNA methylation was analysed on umbilical tissue in 19
AGA and 27 LGA infants. At birth, LGA infants had greater weight (p < 0.0001),
length (p < 0.0001), ponderal index (p = 0.020), as well as greater head (p <
0.0001), chest (p = 0.044), and abdominal (p = 0.007) circumferences than AGA
newborns. LGA infants were still larger at the age of 3 months, but by age 6
months there were no more differences between groups, due to higher length and
weight increments in AGA infants between 0 and 6 months (p < 0.0001 and p =
0.002, respectively). Genome-wide analysis showed no epigenetic differences
between LGA and AGA infants. Overall, LGA infants had slower growth in early
infancy, being anthropometrically similar to AGA infants by 6 months of age. In
addition, differences between AGA and LGA newborns were not associated with
epigenetic changes.
PMID- 26419815
TI - Stoma accessories and quality of life.
PMID- 26419817
TI - ASCN welcomes delegates to its annual conference.
PMID- 26419816
TI - Psychosocial impact of intestinal failure: a familial perspective.
AB - Intestinal failure is a complicated long-term condition that can have profound
physical and psychosocial consequences for a patient's life. Hospitalisation can
be long, with many distressing and unpleasant medical procedures being endured.
Patients often have to deal with large volumes of unmanageable faecal fluid from
stomas or fistulae and usually require home parenteral nutrition (HPN) for the
remainder of their life. The literature focuses on how patients often have to
tolerate long periods of suffering, which can be the basis for significant
emotional anguish. It also addresses how the condition can contribute to myriad
psychosocial difficulties, which can have devastating effects on their body image
and quality of life. However, there is a lack of information regarding the
effects of this condition on the family, who not only have to provide ongoing
support for the patient, but also have to attempt to function normally while
coping with their own fears and emotions. This article reviews the experiences of
two patients, father and daughter, living with intestinal failure; it discusses
their experiences and reveals how they cope with the physical aspects. It also
addresses how the condition can effect psychosocial disturbances, not only for
them but for those living closely with them. The article addresses ways that
nurses could develop their relationship with the patient, enabling them to
recognise and act early on signs of emotional malady.
PMID- 26419818
TI - Meeting the needs of new ostomists: a patient evaluation survey.
AB - Nottingham University Hospitals (NUH) NHS Trust provides a care pathway for
patients undergoing stoma formation surgery, with the stoma care nurse
specialists providing ongoing support for patients, alongside the rest of the
multidisciplinary team, from the preoperative consultation through to their
community follow-up. In the past, the community service offered has not always
been well-received and the whole pathway has not been evaluated in depth to date.
This article reports on a patient evaluation survey of the stoma care pathway at
NUH. The results showed that overall patients are very complimentary of the
service offered to them by the stoma care team. They highly commend the stoma
care nurse specialist. Two areas for amendment in the pathway have been
identified: information provision and the length of time available for the stoma
care nurse specialist to spend one-to-one with each patient. The results of this
survey will aid the team in implementing positive changes to the stoma care
pathway.
PMID- 26419820
TI - Transmembrane prostatic acid phosphatase (TMPAP) delays cells in G1 phase of the
cell cycle.
AB - BACKGROUND: Prostate adenocarcinoma is the most common form of prostate cancer.
We have previously shown in a murine model that prostatic acid phosphatase (PAP)
deficiency leads to increased cell proliferation and development of prostate
adenocarcinoma. The association between PAP and prostate cancer has been
reported. Indeed, high PAP enzymatic activity is detected in the serum of
patients with metastatic disease while its expression is reduced in prostate
cancer tissue. However, the molecular mechanisms behind the onset of the disease
remains poorly understood. We previously identified a novel transmembrane
prostatic acid phosphatase (TMPAP) isoform, which interacts with snapin. TMPAP is
expressed on the plasma membrane, as well as endosomal/lysosomal and exosomal
membrane vesicles by means of a tyrosine-based lysosomal targeting motif
(Yxxphi). METHODS: We used stable overexpression of the secreted isoform (SPAP)
and TMPAP in LNCaP cells, live cell imaging, microarray and qRT-PCR analyses, and
fluid phase uptake of HRP and transferrin. RESULTS: Our results indicate that the
stable overexpression of TMPAP, but not SPAP in LNCaP cells reduces cell growth
while increasing endo/exocytosis and cell size. Specifically, cells
overexpressing TMPAP accumulate in the G1 phase of the cell cycle, and show
altered gene expression profile. CONCLUSIONS: Our data suggests that TMPAP may
function as a non-canonical tumor suppressor by delaying cell growth in G1 phase
of the cell cycle.
PMID- 26419821
TI - Fast switching from isotropic liquids to nematic liquid crystals: rotaxanes as
smart fluids.
AB - We examine a solution of rod-like piston-rotaxanes, which can switch their length
by external excitation (for example optically) from a short state of length L to
a long state of length qL. We show that this solution can exhibit a number of
different behaviours. In particular it can rapidly switch from an isotropic to a
nematic liquid crystalline state. There is a minimum ratio q* = 1.13 for which
transitions from a pure isotropic state to a pure nematic state are possible. We
present a phase-switching diagram, which gives the six possible behaviours for
this system. It turns out that a large fraction of the phase switching diagram is
occupied by the transition from a pure isotropic to a pure nematic state.
PMID- 26419819
TI - Preclinical models of pancreatic ductal adenocarcinoma.
AB - Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult human
malignancies to treat. The 5-year survival rate of PDA patients is 7% and PDA is
predicted to become the second leading cancer-related cause of death in the USA.
Despite intensive efforts, the translation of findings in preclinical studies has
been ineffective, due partially to the lack of preclinical models that faithfully
recapitulate features of human PDA. Here, we review current preclinical models
for human PDA (eg human PDA cell lines, cell line-based xenografts and patient
derived tumour xenografts). In addition, we discuss potential applications of the
recently developed pancreatic ductal organoids, three-dimensional culture systems
and organoid-based xenografts as new preclinical models for PDA.
PMID- 26419822
TI - Response to: 'Baseline differences in SAVOR trial'-- prespecified vs. post hoc
analysis--a potential source of bias.
PMID- 26419823
TI - The yield of screening symptomatic contacts of multidrug-resistant tuberculosis
cases at a tertiary hospital in Addis Ababa, Ethiopia.
AB - BACKGROUND: Early detection and treatment of multidrug-resistant tuberculosis
(MDR-TB, resistant to isoniazid and rifampicin) is an urgent global priority.
Identifying and tracing close contacts of patients with MDR-TB could be a
feasible strategy to achieve this goal. However, there is limited experience with
contact tracing among patients with drug-resistant tuberculosis both globally and
in Ethiopia. Here we present our findings on the extent of screening symptomatic
contacts and its yield in a tertiary hospital in a major urban setting in
Ethiopia. RESULTS: Symptomatic household contacts were identified in 29 (5.7%) of
508 index cases treated at the hospital. There were a total of 155 family members
in the households traced of whom 16 (10%) had confirmed MDR-TB. At least one
confirmed MDR-TB cases was identified in 15 (51.7%) of the 29 traced households.
CONCLUSIONS: Tracing symptomatic contacts of MDR-TB cases could be a high yield
strategy for early detection and treatment of MDR-TB cases in the community. The
approach should be promoted for wider adoption and dissemination. Larger scale
studies should be done to determine its effectiveness and sustainability in
similar settings.
PMID- 26419824
TI - Mifepristone and misoprostol compared with misoprostol alone for induction of
labor in intrauterine fetal death: A randomized trial.
AB - AIM: To assess whether mifepristone and misoprostol are more beneficial than
misoprostol alone for the induction of labor in women with intrauterine fetal
death. METHODS: A randomized double blind placebo-controlled parallel group
superiority trial was conducted. One hundred and ten women who had experienced
fetal death at or later than 20 weeks of gestation were randomized by computer
generated random number sequence to receive 200 mg of mifepristone or matched
placebo tablets orally. Misoprostol was administered vaginally to women of both
groups after 36-48 h. The main outcomes studied were the fetal-placental delivery
rate within 24 hours of commencement of the first dose of misoprostol without
additional intervention and the induction-delivery interval. RESULTS: Successful
delivery occurred significantly more frequently in women who received
mifepristone prior to misoprostol than in women who received only misoprostol
(92.5% [49/53] compared with 71.2% [37/52] respectively; P = 0.001). The mean
induction-delivery interval was also significantly shorter when using
mifepristone plus misoprostol than using misoprostol alone (9.8 h, standard
deviation, 4.4 compared with 16.3 h standard deviation, 5.7, respectively; P <
0.001). CONCLUSION: Use of a combination of mifepristone and misoprostol
significantly improved the rate of successful delivery and shortened the
induction-delivery interval in women who had experienced fetal death compared
with the use of misoprostol alone.
PMID- 26419825
TI - Similarities in murine infection and immune response to Borrelia bissettii and
Borrelia burgdorferi sensu stricto.
AB - In 1982, Borrelia burgdorferi sensu stricto (ss) was identified as the
aetiological agent of Lyme disease. Since then an increasing number of Borrelia
burgdorferi sensu lato (sl) species have been isolated in the United States. To
date, many of these species remain understudied despite mounting evidence
associating them with human illness. Borrelia bissettii is a spirochaete closely
related to B. burgdorferi that has been loosely associated with human illness.
Using an experimental murine infection model, we compared the infectivity and
humoral immune response with a North American isolate of B. bissettii and B.
burgdorferi using culture, molecular and serological methods. The original B.
bissettii cultures were unable to infect immunocompetent mice, but were confirmed
to be infectious after adaptation in immunodeficient animals. B. bissettii
infection resulted in spirochaete burdens similar to B. burgdorferi in skin,
heart and bladder whereas significantly lower burdens were observed in the joint
tissues. B. bissettii induced an antibody response similar to B. burgdorferi as
measured by both immunoblotting and the C6 ELISA. Additionally, this isolate of
B. bissettii was sequenced on the Ion Torrent PGM, which successfully identified
many genes orthologous to mammalian virulence factors described in B.
burgdorferi. Similarities seen between both infections in this well-characterized
murine model contribute to our understanding of the potential pathogenic nature
of B. bissettii. Infection dynamics of B. bissettii, and especially the induced
humoral response, are similar to B. burgdorferi, suggesting this species may
contribute to the epidemiology of human borreliosis.
PMID- 26419826
TI - Recovering the superficial microvascular pattern via diffuse reflection imaging:
phantom validation.
AB - BACKGROUND: Diffuse reflection imaging could potentially be used to recover the
superficial microvasculature under cutaneous tissue and the associated blood
oxygenation status with a modified imaging resolution. The aim of this work is to
deliver a new approach of local off-axis scanning diffuse reflection imaging,
with the revisit of the modified Beer-Lambert Law (MBLL). METHODS: To validate
this, the system is used to recover the micron-scale subsurface vessel structure
interiorly embedded in a skin equivalent tissue phantom. This vessel structure is
perfused with oxygenated meta-hemoglobin solution. RESULTS: Our preliminary
results confirm that the thin vessel structure can be mapped into a 2-D planar
image. The distributions of oxygenated hemoglobin concentration ([Formula: see
text]) and deoxygenated hemoglobin concentration ([Formula: see text]) can be co
registerated through the MBLL upon the CW spectroscopy, the scattering issue is
addressed in the reformed MBLL. The recovered pattern matches to the estimation
from the simultaneous optical coherence tomography studies. CONCLUSIONS: With
further modification, this system may serve as the first prototype to investigate
the superficial microvasculature in the expotential skin cancer loci, or a micro
lesion of vascular dermatosis.
PMID- 26419827
TI - Perceptions and intentions relating to seeking help for depression among medical
undergraduates in Sri Lanka: a cross-sectional comparison with non-medical
undergraduates.
AB - BACKGROUND: This study attempts to understand whether medical undergraduates in
Sri Lanka would seek help for depression. This was done by examining their
perceptions and intentions relating to seeking help for depression, using the
responses of non-medical undergraduates as the baseline for comparison. METHOD:
Medical (n = 620) and non-medical undergraduates (n = 4050) at the University of
Colombo responded to a questionnaire which included a vignette about a depressed
undergraduate, a depression measure, an open-ended question examining their
intentions to seek help if affected by the problem described in the vignette, and
scales examining their perceptions about the helpfulness of various help-seeking
options for dealing with the problem. The latter items were also administered
among mental health professionals to assess expert opinion on dealing with
depression. Logistic regression models were used to examine if medical
undergraduates differed from non-medical undergraduates in their rates of
depression, help-seeking perceptions and help-seeking intentions. These models
were also used to examine if being depressed was associated with differences in
the help-seeking perceptions and intentions of medical undergraduates. RESULTS:
Medical and non-medical undergraduates did not differ in their odds of being
depressed. Overall, the medical undergraduates were more likely to appraise
professional help positively. However, they did not differ from non-medical
undergraduates in relation to their intentions to seek such help if affected by
the problem personally. They were also more likely to indicate their intentions
to seek help from parents and family. Furthermore, medical undergraduates who
screened positive for Major Depression were less likely to appraise some of the
recommended professional and informal help-seeking options as being 'helpful',
with only 50 % considering that it was 'unhelpful' to deal with the problem
alone. There was also no difference in their help-seeking intentions as compared
to those screening negative for Major Depression. DISCUSSION AND CONCLUSIONS:
Although medical training seems to be associated with better help-seeking
beliefs, interventions are needed to improve these medical undergraduates'
intentions to personally seek professional help for depression. It is concerning
that medical undergraduates who are depressed might be less likely to consider it
beneficial to seek help and instead, deal with the problem alone.
PMID- 26419829
TI - The idiopathic preterm delivery methylation profile in umbilical cord blood DNA.
AB - BACKGROUND: Preterm delivery is the leading cause of neonatal morbidity and
mortality. Two-thirds of preterm deliveries are idiopathic. The initiating
molecular mechanisms behind spontaneous preterm delivery are unclear. Umbilical
cord blood DNA samples are an easy source of material to study the neonatal state
at birth. DNA methylation changes can be exploited as markers to identify
spontaneous preterm delivery. To identify methylation differences specific to
idiopathic preterm delivery, we assessed genome-wide DNA methylation changes in
24 umbilical cord blood samples (UCB) using the 450 K Illumina methylation array.
After quality control, conclusions were based on 11 term and 11 idiopathic
preterm born neonates. The differentially methylated positions (DMPs) specific
for preterm/term delivery, neonatal sex, use of oxytocin and mode of initiation
of labor were calculated by controlling the FDR p value at 0.05. RESULTS: The
analysis identifies 1855 statistically significant DMPs between preterm and term
deliveries of which 508 DMPs are also attributable to clinical variables other
than preterm versus term delivery. 1347 DMPs are unique to term vs preterm
delivery, of which 196 DMPs do not relate to gestational age as such. Pathway
analysis indicated enrichment of genes involved in calcium signalling, myometrial
contraction and relaxation pathways. The 1151 DMPs that correlate with advancing
gestational age (p < 0.05) include 161 DMPs that match with two previously
reported studies on UCB methylation. Additionally, 123 neonatal sex specific
DMPs, 97 DMPs specific to the induction of labour and 42 DMPs specific to the
mode of initiation of labor were also identified. CONCLUSION: This study
identifies 196 DMPs in UCB DNA of neonates which do not relate to gestational age
or any other clinical variable recorded and are specific to idiopathic preterm
delivery. Furthermore, 161 DMPs from our study overlap with previously reported
studies of which a subset is also reported to be differentially methylated at 18
years of age. A DMP on MYL4, encoding myosin light chain 4, is a robust candidate
for the identification of idiopathic preterm labour as it is identified by all 3
independent studies.
PMID- 26419830
TI - 7-Ketocholesterol-induced lysosomal dysfunction exacerbates vascular smooth
muscle cell calcification via oxidative stress.
AB - Vascular calcification is known to reduce the elasticity of aorta. Several
studies have suggested that autophagy-lysosomal pathway (ALP) in vascular smooth
muscle cells (VSMCs) is associated with vascular calcification. A major component
of oxidized low-density lipoproteins, 7-ketocholesterol (7-KC), has been reported
to promote inorganic phosphorus (Pi)-induced vascular calcification and induce
ALP. The aim of this study was to unravel the relationship between ALP and the
progression of calcification by 7-KC. Calcification of human VSMCs was induced by
Pi stimulation in the presence or absence of 7-KC. FACS analysis showed that 7-KC
induced apoptosis at a high concentration (30 MUM), but not at a low
concentration (15 MUM). Interestingly, 7-KC promoted calcification in VSMCs
regardless of apoptosis. Immunoblotting and immunostaining showed that 7-KC
inhibits not only the fusion of autophagosomes and lysosomes but also causes a
swell of lysosomes with the reduction of cathepsin B and D. Moreover, lysosomal
protease inhibitors exacerbated the apoptosis-independent calcification by 7-KC
although inhibition of autophagosome formation by Atg5 siRNA did not. Finally,
the 7-KC-induced progression of calcification was alleviated by the treatment
with antioxidant. Taken together, our data showed that 7-KC promotes VSMC
calcification through lysosomal-dysfunction-dependent oxidative stress.
PMID- 26419831
TI - Preoperative and Intraoperative Factors for Early Failure of Native Arteriovenous
Fistulas.
AB - The aim of the study was to assess the potential predictive factors for early
arteriovenous fistula (AVF) failure following the fistula first initiative. We
retrospectively reviewed the data of 159 end-stage renal disease (ESRD) patients
who underwent AVF creation. The preoperative factors such as demographic,
comorbidity condition, laboratory parameters and medication, and intraoperative
or surgical-related factors were assessed. In multivariate logistic regression
analysis, significant predictive factors of early AVF failure were female gender
(odds ratio (95% confidence interval): 2.63 (1.19-5.81); P = 0.017), higher body
mass index (P = 0.038), and lower hemoglobin level (P = 0.048), while adjusting
for preoperative factors or all factors. For adjusting of intraoperative factors,
reduced venous diameter (P = 0.056) tended to be associated with early AVF
failure. In conclusion, female gender, higher body mass index and lower
hemoglobin level predicted the occurrence of early AVF failure in ESRD patients.
PMID- 26419828
TI - Cortical tau load is associated with white matter hyperintensities.
AB - INTRODUCTION: Cerebral white matter lesions (WML), visualized as white matter
hyperintensities (WMH) on T2-weighted MRI, encompass structural damage and loss
of integrity of the cerebral white matter (WM) and are commonly assumed to be
associated with small vessel disease (SVD). However, it has been suggested that
WM damage may also be the result of degenerative axonal loss that is secondary to
cortical Alzheimer's disease (AD) pathologies i.e., hyperphosphorylated tau
(HPtau) and amyloid-beta (Abeta). Here we investigate the influence of HPtau,
Abeta and SVD on WMH severity. RESULTS: 36 human post-mortem right fixed cerebral
hemispheres (mean age 84.4 +/- 7.7 years; male: 16, female: 20) containing
varying amounts of AD-pathology (AD: 23, controls: 13) underwent T2- weighted MRI
with WMH assessed according to the age related white matter change scale (ARWMC).
After dissection, using tissue samples from the frontal, temporal, parietal and
occipital regions from the right hemisphere, we quantitatively assessed cortical
HPtau and Abeta pathology burden by measuring the percentage area covered by AT8
immunoreactivity (HPtau-IR) and 4G8 immunoreactivity (Abeta-IR), and assessed the
severity of WM SVD by calculating the sclerotic index (SI) of WM
arteries/arterioles. HPtau-IR, Abeta-IR, and SI were compared with ARWMC scores.
HPtau-IR, Abeta-IR and WM ARWMC scores were all significantly higher in AD cases
compared to controls, while SI values were similar between groups. ARWMC scores
correlated with HPtau-IR, Abeta-IR and SI in various regions, however, linear
regression revealed that only HPtau-IR was a significant independent predictor of
ARWMC scores. CONCLUSIONS: Here we have shown that increasing cortical HPtau
burden independently predicted the severity of WMH indicating its potentially
important role in the pathogenesis of WM damage. Moreover, our findings suggest
that in AD patients the presence of WMH may indicate cortical AD-associated
pathology rather than SVD. Further studies are warranted to elucidate the
pathological processes that lead to WM damage and to clarify if WMH may serve as
a general biomarker for cortical AD-associated pathology.
PMID- 26419832
TI - Thrombolytic therapy for pulmonary embolism.
AB - BACKGROUND: Thrombolytic therapy (powerful anticoagulation drugs) is usually
reserved for patients with clinically serious or massive pulmonary embolism (PE).
Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly
than heparin and reduce the death rate associated with PE. However, there are
still concerns about the possible risk of adverse effects of thrombolytic
therapy, such as major or minor haemorrhages. This is the second update of the
Cochrane review first published in 2006. OBJECTIVES: To assess the effects of
thrombolytic therapy in patients with acute pulmonary embolism. SEARCH METHODS:
For this update the Cochrane Vascular Group searched their Specialised Register
(last searched September 2014) and the Cochrane Central Register of Controlled
Trials (CENTRAL) in the Cochrane Library (last searched Issue 8, 2014). We also
searched individual trial collections and private databases, along with
bibliographies of relevant articles. We handsearched relevant medical journals.
SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared
thrombolytic therapy followed by heparin versus heparin alone, heparin plus
placebo or surgical intervention in patients with acute PE. We did not include
trials comparing two different thrombolytic agents or different doses of the same
thrombolytic drug. DATA COLLECTION AND ANALYSIS: Two authors (BD and QH) assessed
the eligibility and quality of trials and extracted data. MAIN RESULTS: We
identified 18 trials with a total of 2197 participants for inclusion in the
review. We were not able to include one study in the meta-analysis because it had
no data to extract. Most of the studies carried a high risk of bias because of
high or unclear risk relating to randomisation and blinding. Meta-analysis showed
that, compared with heparin alone, or heparin plus placebo, thrombolytics plus
heparin can reduce the odds of death (odds ratio (OR) 0.57, 95% confidence
interval (CI) 0.37 to 0.87, P = 0.02, low quality evidence) and recurrence of PE
(OR 0.51; 95% CI 0.29 to 0.89, P = 0.02, low quality evidence). The effects of
death weakened when we excluded four studies at high risk of bias from analysis:
OR 0.66, 95% CI 0.42 to 1.06, P = 0.08. The incidence of major and minor
haemorrhagic events was higher in the thrombolytics group than in the control
group, and this difference was statistically significant (OR 2.90, 95% CI 1.95 to
4.31, P < 0.001, low quality evidence; OR 3.09, 95% CI 1.58 to 6.06, P = 0.001,
very low quality evidence, respectively). Length of hospital stay (mean
difference (MD) -1.35, 95% CI -4.27 to 1.58) and quality of life were similar
between the two treatment groups. Stroke was reported in one study and occurred
more often in the thrombolytics group than in the control group, although the
confidence interval was wide (OR 12.10, 95% CI 1.57 to 93.39). Limited
information from a small number of trials indicated that thrombolytics may
improve haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram
assessment, echocardiograms, pulmonary hypertension, coagulation parameters,
clinical outcomes and survival time to a greater extent than heparin alone.
However, the heterogeneity of the studies and small number of participants
involved warrant caution when interpreting results. Similarily, fewer patients
from the thrombolytics group required escalation of treatment. None of the
included studies reported on post-thrombotic syndrome or compared the cost of the
different treatments. AUTHORS' CONCLUSIONS: There is low quality evidence that
thrombolytics reduce death following acute pulmonary embolism compared with
heparin. Furthermore, thrombolytic therapies included in the review were
heterogeneous. Thrombolytic therapy may be helpful in reducing the recurrence of
pulmonary emboli but may cause more major and minor haemorrhagic events and
stroke. More high quality double blind RCTs assessing safety and cost
effectiveness are required.
PMID- 26419833
TI - Heavy metals and its chemical speciation in sewage sludge at different stages of
processing.
AB - The analysis of heavy metal concentrations and forms in sewage sludge constitutes
an important issue in terms of both health and environmental hazards the metals
pose. The total heavy metals concentration enables only the assessment of its
contamination. Hence the knowledge of chemical forms is required to determine
their environmental mobility and sludge final disposal. Heavy metals speciation
was studied by using four-stage sequential extraction BCR (Community Bureau of
Reference). This study was aimed at determining the total concentration of
selected heavy metals (Zn, Cu, Ni, Pb, Cd, Cr and Hg) and their chemical forms
(except for Hg) in sludge collected at different stages of its processing at two
municipal Wastewater Treatment Plants in southern Poland. Metals contents in
sludge samples were determined by using flame atomic absorption spectrometry
(FAAS) and electrothermal atomic absorption spectrometry (ETAAS). This study
shows that Zn and Cu appeared to be the most abundant in sludge, while Cd and Hg
were in the lowest concentrations. The sewage sludge revealed the domination of
immobile fractions over the mobile ones. The oxidizable and residual forms were
dominant for all the heavy metals. There was also a significant difference in
metals speciation between sludges of different origin which was probably due to
differences in wastewater composition and processes occurring in biological stage
of wastewater treatment. The results indicate a negligible capability of metals
to migrate from sludge into the environment. Our research revealed a significant
impact of thickening, stabilization and hygienization on the distribution of
heavy metals in sludge and their mobility.
PMID- 26419834
TI - A critical review of in vitro dosimetry for engineered nanomaterials.
AB - A major obstacle in the development of accurate cellular models for investigating
nanobio interactions in vitro is determination of physiologically relevant
measures of dose. Comparison of biological responses to nanoparticle exposure
typically relies on administered dose metrics such as mass concentration of
suspended particles, rather than the effective dose of particles that actually
comes in contact with the cells over the time of exposure. Adoption of recently
developed dosimetric methodologies will facilitate determination of effective
dose delivered to cells in vitro, thereby improving the accuracy and reliability
of in vitro screening data, validation of in vitro with in vivo data, and
comparison across multiple datasets for the large variety of nanomaterials
currently in the market.
PMID- 26419835
TI - Highly Efficient Organocatalyzed Conversion of Oxiranes and CO2 into Organic
Carbonates.
AB - Invited for the cover of this issue is the group of Arjan Kleij at the Institute
of Chemical Research of Catalonia (ICIQ). The image shows how naturally occurring
compounds such as tannic acid can be used to devise highly efficient CO2
conversion catalysis. The Full Paper itself is available at
10.1002/cssc.201500710.
PMID- 26419836
TI - Dimethyl Sulfide-Dimethyl Ether and Ethylene Oxide-Ethylene Sulfide Complexes
Investigated by Fourier Transform Microwave Spectroscopy and Ab Initio
Calculation.
AB - The ground-state rotational spectra of the dimethyl sulfide-dimethyl ether (DMS
DME) and the ethylene oxide-ethylene sulfide (EO-ES) complexes were observed by
Fourier transform microwave spectroscopy, and a-type and c-type transitions were
assigned for the normal, (34)S, and three (13)C species of the DMS-DME and a-type
and b-type transitions for the normal, (34)S, and two (13)C species of the EO-ES
complexes. The transition frequencies measured for both the complexes were
analyzed by using an S-reduced asymmetric-top rotational Hamiltonian. The
rotational parameters thus derived for the DMS-DME were found to be consistent
with a structure of Cs symmetry with the DMS bound to the DME by two C-H(DMS)...O
and one S...H-C(DME) hydrogen bonds. Some high-Ka lines were found to be split,
and we have interpreted these splittings in terms of internal rotations of the
two methyl groups of the DMS and of the "free", i.e., outer group, of the DME.
Some forbidden transitions were also observed in cases where Ka = 3 levels were
involved, for the DMS-DME complex in the internal-rotation E state. The barrier
height, V3, to internal rotation of the CH3 in the DME thus derived is smaller
than that of the DME monomer, while the V3 of the CH3 groups in the DMS is nearly
the same as that of the DMS monomer. For the EO-ES complex, the observed data
were interpreted in terms of an antiparallel structure of Cs symmetry with the EO
bound to the ES by two C-H(ES)...O and two S...H-C(EO) hydrogen bonds. An attempt
was also made to observe a-type transitions of the DMS dimer without success. We
have applied a natural bond orbital analysis to the DMS-DME and EO-ES to
calculate the stabilization energy CT (= DeltaEsigmasigma*), which was correlated
closely with the binding energy as found for other related complexes.
PMID- 26419837
TI - Endoscopic Z-plasty for Treatment of Supraglottic Stenosis: A New Technique.
PMID- 26419838
TI - Predictors of Nodal Metastasis in Parotid Malignancies: A National Cancer Data
Base Study of 22,653 Patients.
AB - OBJECTIVE: (1) To identify predictors of nodal disease in parotid malignancies
using various clinical and pathologic variables. (2) To examine the effect of
nodal disease on overall survival (OS) in parotid cancers STUDY DESIGN:
Retrospective database review. SETTING: National Cancer Data Base (1998-2012).
SUBJECTS AND METHODS: We identified all cases of primary parotid malignancies in
the United States between 1998 and 2012 in the National Cancer Data Base. Eight
histopathologies, constituting >80% of all cases, were examined for nodal
metastasis and survival. RESULTS: We identified 22,653 cases of primary parotid
cancer. Eight major histologies were studied, with mucoepidermoid carcinoma
(31%), acinic cell carcinoma (18%), adenocarcinoma (14%), and adenoid cystic
carcinoma (9%) being most common. Regional nodal disease incidence was 24.4%
overall and varied by histopathology. Salivary ductal carcinoma had the highest
incidence of both nodal metastasis and occult lymph node metastasis. Overall, N0
patients lived significantly longer than N+ (5-year OS, 79% vs 40%; P < .001).
Low-grade disease had significantly better survival than high-grade (5-year OS,
88% vs 69%; P < .001). Occult nodal disease was found in 10.2% and varied by
histopathology. CONCLUSION: Regional lymph node metastasis significantly
decreases survival in many parotid malignancies. High-grade cancers had higher
incidences of regional disease than did low grade. Adenocarcinoma had the highest
mortality when regional disease was present. Incidence of occult disease varied
by histology, but incidence was <10% for all low-grade disease. High T stage and
grade are significant independent predictors of nodal disease for most
histopathologies.
PMID- 26419839
TI - Cisplatin-Induced Ototoxicity and the Effects of Intratympanic Diltiazem in a
Mouse Model.
AB - OBJECTIVE: To evaluate whether the calcium-channel blocker diltiazem has
protective effects against cisplatin-induced ototoxicity in a mouse model. STUDY
DESIGN: Original basic science in vivo investigation. SETTING: Academic setting:
Otolaryngology-Head and Neck Surgery laboratory at University of Connecticut
Health Center. SUBJECTS: Thirty-nine female CBA/J mice. METHODS: Pure tone- or
click-evoked auditory brainstem responses (ABRs) were recorded in CBA/J mice to
determine auditory thresholds. All mice had baseline ABRs recorded. They were
then given a single cisplatin bolus (14 mg/kg), followed by 5 consecutive days of
intratympanic diltiazem or saline control. Follow-up thresholds were recorded on
days 7, 14, and 21 postcisplatin. Tone-evoked ABRs evaluated the otoprotective
effect of 2-mg/kg diltiazem in 9 mice, and dose effect was examined in response
to click-evoked ABR with 2- or 4-mg/kg diltiazem in 2 groups of 15 mice. RESULTS:
Saline-treated ears had significantly elevated tone-evoked auditory thresholds
when compared with diltiazem-treated ears (P = .038) on day 7 postcisplatin only.
Click-evoked ABR thresholds were significantly elevated in saline-treated ears
versus diltiazem-treated ears for the 2-mg/kg group (P = .001) and 4-mg/kg group
(P = .011) on days 7, 14, and 21 postcisplatin. CONCLUSION: Intratympanic
diltiazem has significant protective effects against cisplatin ototoxicity at 2
and 4 mg/kg. This is the first in vivo study to demonstrate that diltiazem offers
a potentially novel therapy for cisplatin-induced ototoxicity.
PMID- 26419840
TI - Medicolegal Aspects of Iatrogenic Dysphonia and Recurrent Laryngeal Nerve Injury.
AB - OBJECTIVE: To examine aspects of litigation involving iatrogenic dysphonia and
injury to the recurrent laryngeal nerve in the adult population. STUDY DESIGN:
Legal database review. SETTING: Medicolegal judicial system. SUBJECTS AND
METHODS: Jury verdicts and settlement reports listing voice impairment or
recurrent laryngeal nerve dysfunction as a primary injury in adult patients were
identified in the Westlaw Database. Reports were examined for plaintiff
demographics, defendant specialty, procedure performed, rates of settlements and
verdicts, monetary awards, primary plaintiff symptoms, and common allegations.
RESULTS: A total of 123 jury verdict and settlement reports were identified.
General surgeons (24%), otolaryngologists (20%), and anesthesiologists (18%) were
involved in the majority of cases. The procedure causing the alleged injury was
primarily thyroidectomy (34%), followed by intubation (18%) and spinal
instrumentation (10%). The majority of cases (70%) were decided in favor of the
defendant. Where monetary awards were recorded, settlements and jury verdicts in
favor of the plaintiff ranged between $4250 and $3,000,000, with a mean of
$788,713. In addition to voice disturbances, complaints of dyspnea and dysphagia
were commonly listed alleged injuries. The only factors associated with plaintiff
verdicts were general surgery specialty (odds ratio, 6.3; 95% confidence
interval, 1.7-23.2) and claims of loss of consortium (odds ratio, 8.5; 95%
confidence interval, 1.2-60.7). CONCLUSION: Dysphonia is a common complication in
a number of procedures across multiple specialties. Although the majority of
cases are decided in favor or the defendant, payments awarded can be
considerable. Awareness of factors involved in these medical malpractice cases
can help limit physician liability.
PMID- 26419841
TI - Differential Effects of HRAS Mutation on LTP-Like Activity Induced by Different
Protocols of Repetitive Transcranial Magnetic Stimulation.
AB - BACKGROUND: Costello syndrome (CS) is a rare congenital disorder due to a G12S
amino acid substitution in HRAS protoncogene. Previous studies have shown that
Paired Associative Stimulation (PAS), a repetitive brain stimulation protocol
inducing motor cortex plasticity by coupling peripheral nerve stimulation with
brain stimulation, leads to an extremely pronounced motor cortex excitability
increase in CS patients. Intermittent Theta Burst Stimulation (iTBS) represents a
protocol able to induce motor cortex plasticity by trains of stimuli at 50 Hz. In
healthy subjects PAS and iTBS produce similar after-effects in motor cortex
excitability. Experimental models showed that HRAS-dependent signalling pathways
differently affect LTP induced by different patterns of repetitive synaptic
stimulation. OBJECTIVE: We aimed to compare iTBS-induced after-effects on motor
cortex excitability with those produced by PAS in CS patients and to observe
whether HRAS mutation differentially affects two different forms of
neuromodulation protocols. METHODS: We evaluated in vivo after-effects induced by
PAS and iTBS applied over the right motor cortex in 4 CS patients and in 21
healthy age-matched controls. RESULTS: Our findings confirmed HRAS-dependent
extremely pronounced PAS-induced after-effects and showed for the first time that
iTBS induces no change in MEP amplitude in CS patients whereas both protocols
lead to an increase of about 50% in controls. CONCLUSIONS: CS patients are
characterized by an impairment of iTBS-related LTP-like phenomena besides
enhanced PAS-induced after-effects, suggesting that HRAS-dependent signalling
pathways have a differential influence on PAS- and iTBS-induced plasticity in
humans.
PMID- 26419842
TI - Chemoenzymatic collective synthesis of optically active
hydroxyl(methyl)tetrahydronaphthalene-based bioactive terpenoids.
AB - Starting from succinic anhydride and 2-methylanisole, a chemoenzymatic collective
formal/total synthesis of several optically active tetrahydronaphthalene based
bioactive natural products has been presented via advanced level common
precursors; the natural product and antipode (-)/(+)-aristelegone B.
Regioselective benzylic oxidations, stereoselective introduction of hydroxyl
groups at the alpha-position of ketone moiety in syn-orientation, efficient
enzymatic resolutions with high enantiomeric purity, stereoselective reductions,
samarium iodide induced deoxygenations and tandem acylation-Wittig reactions
without racemization and/or eliminative aromatization were the key features. An
attempted diastereoselective synthesis of (+/-)-vallapin has also been described.
PMID- 26419843
TI - Tumor associated PD-L1 expression pattern in microscopically tumor positive
sentinel lymph nodes in patients with melanoma.
AB - BACKGROUND: Characterization of PD-L1 expression within clinically/radiologically
negative but microscopically tumor positive sentinel lymph nodes (SLN) is
important to our understanding of the relevance of this immune checkpoint pathway
for adjuvant therapy. METHODS: Patients included had primary cutaneous melanoma,
Breslow thickness of 2.01-4.0 or >4 mm with or without tumor ulceration (T3a,
T3b, T4a, T4b). All patients had microscopically tumor positive SLN. Hematoxylin
and eosin (H&E) staining was performed, followed by PD-L1 immunohistochemical
(IHC) staining using a preliminary IHC assay with anti-PD-L1 antibody clone 22C3.
The slides were separately evaluated by two pathologists (JY and CG). Samples
containing metastatic melanoma lesions were scored separately for PD-L1
expression in intratumoral and peritumoral locations, by utilizing two scoring
methods. RESULTS: Twenty-four patients where metastatic melanoma presence in the
SLN was confirmed by H&E review of the cut sections were included in the final
analysis of PD-L1 expression. SLN tumor size ranged from 1 to 2 mm. For three
patients, the melanin content was too high to confidently assign a PD-L1 score.
For the remaining 21 patients, all had some evidence of either intratumoral or
peritumoral PD-L1 expression. The frequency of intratumoral tumor-associated PD
L1 expression was: 0 % of tumor cells (3 pts, 14 %); <1 % (5 pts, 24 %); 1-10 %
(6 pts, 29 %) and >10 % (7 pts, 33 %). CONCLUSIONS: Tumor-associated PD-L1
expression is readily detectable within melanoma micrometastases in the SLN of
the majority of patients. These results support the testing of a therapeutic role
for PD1/PD-L1 inhibition in the adjuvant setting, targeting melanoma
micrometastases.
PMID- 26419844
TI - Implementing a home-based exercise program for patients with advanced, incurable
diseases after discharge and their caregivers: lessons we have learned.
AB - BACKGROUND: Palliative care (PC) patients experience loss of physical function
which usually impedes mobility, autonomy and quality of life. We aimed at
examining the feasibility of a home-based exercise program for patients with
advanced, incurable diseases after discharge. RESULTS: This was a single-arm
pilot study (WHO-ICTRP: DRKS00005048). The 12-week home-based program comprised
strength, balance, flexibility and endurance components. Patients with a presumed
life expectancy of 6-12 months were recruited during a 6-months period on a
specialized PC and a radiation therapy ward. We chose the De Morton Mobility
Index as primary outcome. Secondary outcomes were quality of life, 6-min walk
test and others. A total of 145 patients were screened, 103 (98%) out of 105
patients on the specialized PC ward could not be included, mostly because of a
low performance status [n = 94; 90%; Eastern Cooperative Oncology Group (ECOG)
>2]. The only two eligible patients declined to participate. Eleven out of 40
patients (28%) were eligible on the radiation therapy ward. However, only one
patient (9%) participated but dropped out 2 days later (upcoming surgery).
Distance to the hospital (n = 3; 30%) and considering additional tasks as "too
much" (n = 3; 30%) were most common reasons for non-participation. CONCLUSIONS:
Establishing a home-based exercise program for inpatients after discharge was not
feasible mainly due to non-eligibility and lack of demand. For future trials, we
suggest that choosing (1) outpatients with (2) an ECOG of <=2 and (3) an
estimated survival of >=9 months could enhance participation in home-based
exercise programs.
PMID- 26419845
TI - Endoscopic ultrasound-guided sampling of solid pancreatic masses: 22-gauge
aspiration versus 25-gauge biopsy needles.
AB - BACKGROUND: Biopsy needles have recently been developed to obtain both
cytological and histological specimens during endoscopic ultrasound (EUS). We
conducted this study to compare 22-gauge (G) fine needle aspiration (FNA)
needles, which have been the most frequently used, and new 25G fine needle biopsy
(FNB) needles for EUS-guided sampling of solid pancreatic masses. METHODS: We
conducted a retrospective cohort study of all EUS-guided sampling performed
between June 2010 and October 2013. During the study period, 76 patients with
pancreatic masses underwent EUS-guided sampling with a 22G FNA needle (n = 38) or
a 25G FNB needle (n = 38) for diagnosis. An on-site cytopathologist was not
present during the procedure. Technical success, the number of needle passes,
cytological diagnostic accuracy, cytological sample quality (conventional smear
and liquid-based preparation), histological diagnostic accuracy, and
complications were reviewed and compared. RESULTS: There were no significant
differences in technical success (100% for both), the mean number of needle
passes (5.05 vs. 5.55, P = 0.132), or complications (0% for both) between the 22G
FNA group and the 25G FNB group. The 22G FNA and 25G FNB groups exhibited
comparable outcomes with respect to cytological diagnostic accuracy (97.4% vs.
89.5%, P = 0.358) and histological diagnostic accuracy (34.2% vs. 52.6%, P =
0.105). In the cytological sample quality analysis, the 25G FNB group exhibited
higher scores for the amount of diagnostic cellular material present (22G FNA:
0.92 vs. 25G FNB: 1.32, P = 0.030) and the retention of appropriate architecture
(22G FNA: 0.97 vs. 25G FNB: 1.42, P = 0.010) in the liquid-based preparation. The
25G FNB group showed a better histological diagnostic yield for specific tumor
discrimination compared with the 22G FNA group (60 % vs. 32.4%, P = 0.018).
CONCLUSIONS: Use of the 25G FNB needle was technically feasible, safe, efficient,
and comparable to use of the standard 22G FNA needle in patients with solid
pancreatic masses in the absence of an on-site cytopathologist. The cytological
sample quality in the liquid-based preparation and the histological diagnostic
yield for specific tumor discrimination of EUS-guided sampling using a 25G FNB
needle were significantly higher than those using a 22G FNA needle.
PMID- 26419847
TI - Phosphodiesterase 4 inhibitors for the treatment of chronic obstructive pulmonary
disease: a review of current and developing drugs.
AB - INTRODUCTION: Phosphodiesterase (PDE) inhibitors modulate lung inflammation and
cause bronchodilation by increasing intracellular cyclic adenosine 3', 5'
monophosphate in airway smooth muscle and inflammatory cells. Roflumilast is the
only approved PDE-4 inhibitor (PDE4I) for use in chronic obstructive pulmonary
disease (COPD). Its beneficial clinical effects occur preferentially in patients
with chronic bronchitis and frequent COPD exacerbations. Use of roflumilast as
adjunctive or alternate therapy to other COPD medications reduces exacerbations
and modestly improves lung function. AREAS COVERED: This article reviews the
current role of PDE4I in COPD treatment emphasizing roflumilast's clinical
efficacy and adverse effects. This article also reviews developing PDE4Is in
early clinical trials and in preclinical studies. EXPERT OPINION: After decades
of research in drug development, PDE4Is are a welcomed addition to the COPD
therapeutic armamentarium. In its current clinical role, the salubrious clinical
effects of PDE4I in reducing exacerbations and stabilizing the frequent
exacerbator phenotype have to be cautiously balanced with numerous adverse
effects. Developing drugs may provide similar or better clinical benefits while
minimizing adverse effects by changing the mode of drug delivery to inhaled
formulations, combining dual PDE isoenzyme inhibitors (PDE1/4I and PDE3/4I) and
by forming hybrid molecules with other bronchodilators (muscarinic receptor
antagonist/PDE4I and beta2-agonist/PDE4I).
PMID- 26419848
TI - How to manage pasireotide, when using as medical treatment for Cushing's disease.
PMID- 26419849
TI - Rescue in vitro maturation (IVM) of immature oocytes in stimulated cycles in
women with low functional ovarian reserve (LFOR).
AB - Rescue in vitro maturation (IVM) is currently not a routine procedure in
association with in vitro fertilization (IVF). We compared in a prospectively
cohort study of 10 patients with normal functional ovarian reserve (NFOR) and of
25 with low functional ovarian reserve (LFOR), defined by abnormally high FSH
and/or abnormally low AMH levels), IVM dynamics of immature oocytes. Following
controlled ovarian hyperstimulation in IVF cycles, only immature oocytes
underwent rescue IVM (for up to 48 h). Oocyte maturation dynamics, fertilization
rates, embryo development, and pregnancy rates were then compared between NFOR
and LFOR patients. Though proportion of MI and GV oocytes reaching MII stages
within 48 h and rate of maturation of MI oocytes did not differ, in women with
LFOR significantly more GV oocytes reached MII stage within 24 h (30.4 vs. 66.9
%; P = 0.013), while fertilization rates and embryo generation numbers were
similar between both groups. Rescue IVM, thus, produced 1.5 additional embryos
for transfer in women with LFOR and 1.6 in patients with NFOR, a highly
significant difference in relative improvement in available embryo numbers for
LFOR (+60.0 %) and NFOR women (+16.5 %). Rescue IVM, thus, not only demonstrates
different time dynamics between women with LFOR and NFOR but also
disproportionate efficacy in improving available embryo numbers for transfer in
favor of LFOR patients. 1/7 patients, who reached embryo transfer with only
embryos produced via rescue IVF conceived and delivered, proving that rescue IVF
in women with LFOR also improves pregnancy and delivery chances. Because of the
small number of embryos LFOR patients produce, every additional embryo is of
considerable potential clinical significance for them, suggesting that rescue IVM
in women with LFOR should become routine practice.
PMID- 26419850
TI - Elevated 1-hour plasma glucose levels are associated with dysglycemia, impaired
beta-cell function, and insulin sensitivity: a pilot study from a real world
health care setting.
PMID- 26419846
TI - Understanding the molecular basis of autism in a dish using hiPSCs-derived
neurons from ASD patients.
AB - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder
characterized by deficits in social cognition, language development, and
repetitive/restricted behaviors. Due to the complexity and heterogeneity of ASD
and lack of a proper human cellular model system, the pathophysiological
mechanism of ASD during the developmental process is largely unknown. However,
recent progress in induced pluripotent stem cell (iPSC) technology as well as in
vitro neural differentiation techniques have allowed us to functionally
characterize neurons and analyze cortical development during neural
differentiation. These technical advances will increase our understanding of the
pathogenic mechanisms of heterogeneous ASD and help identify molecular biomarkers
for patient stratification as well as personalized medicine. In this review, we
summarize our current knowledge of iPSC generation, differentiation of specific
neuronal subtypes from iPSCs, and phenotypic characterizations of human ASD
patient-derived iPSC models. Finally, we discuss the current limitations of iPSC
technology and future directions of ASD pathophysiology studies using iPSCs.
PMID- 26419851
TI - [(18)F]FDG PET/CT outperforms [(18)F]FDG PET/MRI in differentiated thyroid
cancer.
AB - PURPOSE: To evaluate the diagnostic potential of PET/MRI with [(18)F]FDG in
comparison to PET/CT in patients with differentiated thyroid cancer suspected or
known to have dedifferentiated. METHODS: The study included 31 thyroidectomized
and remnant-ablated patients who underwent a scheduled [(18)F]FDG PET/CT scan and
were then enrolled for a PET/MRI scan of the neck and thorax. The datasets
(PET/CT, PET/MRI) were rated regarding lesion count, conspicuity, diameter and
characterization. Standardized uptake values were determined for all [(18)F]FDG
positive lesions. Histology, cytology, and examinations before and after
treatment served as the standards of reference. RESULTS: Of 26 patients with a
dedifferentiated tumour burden, 25 were correctly identified by both [(18)F]FDG
PET/CT and PET/MRI. Detection rates by PET/CT and PET/MRI were 97 % (113 of 116
lesions) and 85 % (99 of 113 lesions) for malignant lesions, and 100 % (48 of 48
lesions) and 77 % (37 of 48 lesions) for benign lesions, respectively. Lesion
conspicuity was higher on PET/CT for both malignant and benign pulmonary lesions
and in the overall rating for malignant lesions (p < 0.001). There was a
difference between PET/CT and PET/MRI in overall evaluation of malignant lesions
(p < 0.01) and detection of pulmonary metastases (p < 0.001). Surgical evaluation
revealed three malignant lesions missed by both modalities. PET/MRI additionally
failed to detect 14 pulmonary metastases and 11 benign lesions. CONCLUSION: In
patients with thyroid cancer and suspected or known dedifferentiation, [(18)F]FDG
PET/MRI was inferior to low-dose [(18)F]FDG PET/CT for the assessment of
pulmonary status. However, for the assessment of cervical status, [(18)F]FDG
PET/MRI was equal to contrast-enhanced neck [(18)F]FDG PET/CT. Therefore,
[(18)F]FDG PET/MRI combined with a low-dose CT scan of the thorax may provide an
imaging solution when high-quality imaging is needed and high-energy CT is
undesirable or the use of a contrast agent is contraindicated.
PMID- 26419853
TI - Editor's Comment.
PMID- 26419852
TI - Subacute haematotoxicity after PRRT with (177)Lu-DOTA-octreotate: prognostic
factors, incidence and course.
AB - PURPOSE: In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is
one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted
from (131)I treatment. We investigated the incidence and duration of
haematological toxicity and its risk factors in patients treated with PRRT with
(177)Lu-DOTA(0)-Tyr(3)-octreotate ((177)Lu-DOTATATE). Also, absorbed BM dose
estimates were evaluated and compared with the accepted 2 Gy dose limit. METHODS:
The incidence and duration of grade 3 or 4 haematological toxicity (according to
CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit
(gigabecquerels) of administered radioactivity was calculated and the
correlations between doses to the BM and haematological risk factors were
determined. RESULTS: Haematological toxicity (grade 3/4) occurred in 34 (11 %) of
320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood
transfusions were required. Risk factors significantly associated with
haematological toxicity were: poor renal function, white blood cell (WBC) count
<4.0 * 10(9)/l, age over 70 years, extensive tumour mass and high tumour uptake
on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per
administered activity in 23 evaluable patients was 67 +/- 7 mGy/GBq, resulting in
a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq (177)Lu
DOTATATE. Significant correlations between (cumulative) BM dose and platelet and
WBC counts were found in a selected group of patients. CONCLUSION: The incidence
of subacute haematological toxicity after PRRT with (177)Lu-DOTATATE is
acceptable (11 %). Patients with impaired renal function, low WBC count,
extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age
are more likely to develop grade 3/4 haematological toxicity. The BM dose limit
of 2 Gy, adopted from (131)I, seems not to be valid for PRRT with (177)Lu
DOTATATE.
PMID- 26419855
TI - Ultralight anisotropic foams from layered aligned carbon nanotube sheets.
AB - In this work, we present large scale, ultralight aligned carbon nanotube (CNT)
structures which have densities an order of magnitude lower than CNT arrays, have
tunable properties and exhibit resiliency after compression. By stacking aligned
sheets of carbon nanotubes and then infiltrating with a pyrolytic carbon (PyC),
resilient foam-like materials were produced that exhibited complete recovery from
90% compressive strain. With density as low as 3.8 mg cm(-3), the foam structure
is over 500 times less dense than bulk graphite. Microscopy revealed that PyC
coated the junctions among CNTs, and also increased CNT surface roughness. These
changes in the morphology explain the transition from inelastic behavior to foam
like recovery of the layered CNT sheet structure. Mechanical and thermal
properties of the foams were tuned for different applications through variation
of PyC deposition duration while dynamic mechanical analysis showed no change in
mechanical properties over a large temperature range. Observation of a large and
linear electrical resistance change during compression of the aligned CNT/carbon
(ACNT/C) foams makes strain/pressure sensors a relevant application. The foams
have high oil absorption capacities, up to 275 times their own weight, which
suggests they may be useful in water treatment and oil spill cleanup. Finally,
the ACNT/C foam's high porosity, surface area and stability allow for
demonstration of the foams as catalyst support structures.
PMID- 26419854
TI - Association of Vitamin D With Stress Fractures: A Retrospective Cohort Study.
AB - Vitamin D is an essential, fat-soluble nutrient that is a key modulator of bone
health. Despite the gaining popularity throughout published medical studies, no
consensus has been reached regarding a serum vitamin D level that will guarantee
adequate skeletal health in a patient with an increased functional demand. The
purpose of the present investigation was to examine the serum concentrations of
vitamin D in patients with confirmed stress fractures. A total of 124 patients
were included in our retrospective cohort study. Of the 124 patients, 53 had
vitamin D levels measured within 3 months of diagnosis. An association was seen
in patients with a stress fracture and vitamin D level measured, as 44 (83.02%)
of the 53 patients had a serum 25-hydroxyvitamin D level <40 ng/mL. Although an
association was seen at our institution in patients with stress fractures and a
serum vitamin D concentration <40 ng/mL, a larger and prospective investigation
is warranted to further understand the effect of vitamin D level and stress
fracture prevention in an active, nonmilitary population.
PMID- 26419856
TI - Influence of adiponectin gene variants and plasma fatty acids on systemic
inflammation state association-A cross-sectional population-based study, Sao
Paulo, Brazil.
AB - SCOPE: Interactions between adiponectin genetic variants and plasma fatty acid
profile can modulate plasma inflammatory biomarker concentration and the risk for
metabolic diseases. The aim of this study was to investigate the interaction
between single nucleotide polymorphisms of the adiponectin gene and plasma fatty
acid profile in modulating the odds for systemic inflammation in a cross
sectional population-based study. METHODS AND RESULTS: Inflammatory patterns
comprised 11 inflammatory biomarkers. Among participants of the Health Survey of
Sao Paulo, 262 adults (19-59 years) met the inclusion criteria. Anthropometric
parameters, blood pressure, plasma inflammatory biomarker concentration, and
fatty acid profile were measured and five single nucleotide polymorphisms of the
adiponectin gene (rs2241766, rs1501299, rs16861209, rs17300539, and rs266729)
genotyped. Individuals in the upper 50th percentile for plasma araquidonic acid,
n-3 highly unsaturated fatty acid and estimated delta-5-desaturase activity, had
reduced odds of being in the inflammatory cluster (OR (95% CI) = 0.55 (0.32
0.95), 0.50 (0.28-0.88) and 0.48 (0.28-0.83), respectively). Gene-plasma fatty
acid profile interaction was found between rs2241766 and n-3 (p = 0.019),
rs16861209 and araquidonic acid and docosapentaenoic acid (p = 0.044, p = 0.037,
respectively), and rs17300539 and saturated fatty acid (p = 0.019). CONCLUSION:
Plasma fatty acid profile can interact with adiponectin gene variants to modulate
the risk for systemic inflammatory state.
PMID- 26419857
TI - Implications of free breathing motion assessed by 4D-computed tomography on the
delivered dose in radiotherapy for esophageal cancer.
AB - The aim of this study was to assess the effect of breathing motion on the
delivered dose in esophageal cancer 3-dimensional (3D)-conformal radiotherapy (3D
CRT), intensity-modulated radiotherapy (IMRT), and volumetric modulated arc
therapy (VMAT). We assessed 16 patients with esophageal cancer. All patients
underwent 4D-computed tomography (4D-CT) for treatment planning. For each of the
analyzed patients, 1 3D-CRT, 1 IMRT, and 1 VMAT (RapidArc-RA) plan were
calculated. Each of the 3 initial plans was recalculated on the 4D-CT (for the
maximum free inspiration and maximum free expiration) to assess the effect of
breathing motion. We assessed the minimum dose (Dmin) and mean dose (Dmean) to
the esophagus within the planning target volume, the volume changes of the lungs,
the Dmean and the total lung volume receiving at least 40Gy (V40), and the V30,
V20, V10, and V5. For the heart we assessed the Dmean and the V25. Over all
techniques and all patients the change in Dmean as compared with the planned
Dmean (planning CT [PCT]) to the esophagus was 0.48% in maximum free inspiration
(CT_insp) and 0.55% in maximum free expiration (CT_exp). The Dmin CT_insp change
was 0.86% and CT_exp change was 0.89%. The Dmean change of the lungs (heart) was
in CT_insp 1.95% (2.89%) and 3.88% (2.38%) in CT_exp. In all, 4 patients had a
clinically relevant change of the dose (>= 5% Dmean to the heart and the lungs)
between inspiration and expiration. These patients had a very cranially or
caudally situated tumor. There are no relevant differences in the delivered dose
to the regions of interest among the 3 techniques. Breathing motion management
could be considered to achieve a better sparing of the lungs or heart in patients
with cranially or caudally situated tumors.
PMID- 26419858
TI - Identification of dual-tropic HIV-1 using evolved neural networks.
AB - Blocking the binding of the envelope HIV-1 protein to immune cells is a popular
concept for development of anti-HIV therapeutics. R5 HIV-1 binds CCR5, X4 HIV-1
binds CXCR4, and dual-tropic HIV-1 can bind either coreceptor for cellular entry.
R5 viruses are associated with early infection and over time can evolve to X4
viruses that are associated with immune failure. Dual-tropic HIV-1 is less
studied; however, it represents functional antigenic intermediates during the
transition of R5 to X4 viruses. Viral tropism is linked partly to the HIV-1
envelope V3 domain, where the amino acid sequence helps dictate the receptor a
particular virus will target; however, using V3 sequence information to identify
dual-tropic HIV-1 isolates has remained difficult. Our goal in this study was to
elucidate features of dual-tropic HIV-1 isolates that assist in the biological
understanding of dual-tropism and develop an approach for their detection. Over
1559 HIV-1 subtype B sequences with known tropisms were analyzed. Each sequence
was represented by 73 structural, biochemical and regional features. These
features were provided to an evolved neural network classifier and evaluated
using balanced and unbalanced data sets. The study resolved R5X4 viruses from R5
with an accuracy of 81.8% and from X4 with an accuracy of 78.8%. The approach
also identified a set of V3 features (hydrophobicity, structural and polarity)
that are associated with tropism transitions. The ability to distinguish R5X4
isolates will improve computational tropism decisions for R5 vs. X4 and assist in
HIV-1 research and drug development efforts.
PMID- 26419859
TI - An evaluation study of a gender-specific smoking cessation program to help Hong
Kong Chinese women quit smoking.
AB - BACKGROUND: There is a lack of population-based smoking cessation interventions
targeting woman smokers in Hong Kong, and in Asia generally. This study aimed to
evaluate the effectiveness of a gender-specific smoking cessation program for
female smokers in Hong Kong. METHODS: To evaluate the effectiveness of the
service, a total of 457 eligible smokers were recruited. After the baseline
questionnaire had been completed, a cessation counseling intervention was given
by a trained counselor according to the stage of readiness to quit. Self-reported
seven-day point prevalence of abstinence and reduction of cigarette consumption
(>=50 %) and self-efficacy in rejecting tobacco were documented at one week and
at two, three and six months. RESULTS: The 7-day point prevalence quit rate was
28.4 % (130/457), and 21.9 % (100/457) had reduced their cigarette consumption by
at least 50 % at the six-month follow-up. The average daily cigarette consumption
was reduced from 8.3 at baseline to 6.3 at six months. Moreover, both internal
and external stimuli of anti-smoking self-efficacy increased from baseline to six
months. CONCLUSIONS: The study provides some evidence for the effectiveness of
the gender-specific smoking cessation program for female smokers. Furthermore,
helping smokers to improve their self-efficacy in resisting both internal and
external stimuli of tobacco use can be a way of enhancing the effectiveness of a
smoking cessation intervention.
PMID- 26419860
TI - Design of chemical space networks using a Tanimoto similarity variant based upon
maximum common substructures.
AB - Chemical space networks (CSNs) have recently been introduced as an alternative to
other coordinate-free and coordinate-based chemical space representations. In
CSNs, nodes represent compounds and edges pairwise similarity relationships. In
addition, nodes are annotated with compound property information such as
biological activity. CSNs have been applied to view biologically relevant
chemical space in comparison to random chemical space samples and found to
display well-resolved topologies at low edge density levels. The way in which
molecular similarity relationships are assessed is an important determinant of
CSN topology. Previous CSN versions were based on numerical similarity functions
or the assessment of substructure-based similarity. Herein, we report a new CSN
design that is based upon combined numerical and substructure similarity
evaluation. This has been facilitated by calculating numerical similarity values
on the basis of maximum common substructures (MCSs) of compounds, leading to the
introduction of MCS-based CSNs (MCS-CSNs). This CSN design combines advantages of
continuous numerical similarity functions with a robust and chemically intuitive
substructure-based assessment. Compared to earlier version of CSNs, MCS-CSNs are
characterized by a further improved organization of local compound communities as
exemplified by the delineation of drug-like subspaces in regions of biologically
relevant chemical space.
PMID- 26419861
TI - Indian endocrinologists start debate on diabetes drug.
PMID- 26419862
TI - High Burden of HBV-Infection and Atypical HBV Strains among HIV-infected
Cameroonians.
AB - AIM: To investigate the prevalence and genotypic profile of overt and occult
hepatitis-B infection (OBI) among HIV-infected individuals in Cameroon. METHODS:
212 HIV-infected Cameroonians, aged 37.6 [IQR: 32.6-46.6] followed-up at the
University Health Centre in Yaounde, were tested for HBsAg, anti-HBs, anti-HBc
IgG/IgM, HBV-DNA and anti-HCV IgG. HBV positive cases were tested for Hepatitis
Delta virus (HDV) using anti-HDV IgG and HDV-RNA. Liver function was assessed by
alanine and aspartate aminotransaminases. OBI was defined as negative-HBsAg and
detectable HBV-DNA. In occult or overt HBVinfected participants, HBV reverse
transcriptase (RT)/surface (S) sequences were analyzed for drug resistance,
immuneescape mutants, and phylogeny. RESULTS: Overall, 78.3% (166/212)
participants had past/ongoing HBV-exposure, with 39.1% (83/212) carrying
"HBcAbpositive alone". Prevalence of overt HBV (positive-HBsAg) was 11.8%
(25/212), prevalence of HBV and HDV was respectively 6.9% (12/175) and 12%
(3/25). Phylogeny of HBV-RT/S revealed the co-circulation of genotypes A and E.
All HBV-coinfected participants harbored HBV strains with at least one immune
escape mutation. Of note, one HBV variant carried the vaccine-escape mutation
G145R that hinders HBsAg neutralization by antibodies. For the first time, a
novel 9 aa-deletion (s115-s123), located in the HBsAg "a" determinant, was found
concomitantly with OBI. A stop codon in the S region (associated with increased
risk of hepatocellular carcinoma) was found in six cases. CONCLUSION: High
prevalence of overt/occult HBV-infection and circulating atypical strains
highlight the importance of HBV-surveillance among HIV-infected Cameroonians and
strategies to detect OBI in highly endemic countries.
PMID- 26419863
TI - Elective free flap revision in the head and neck cancer patient: Indications and
outcomes.
AB - Elective free flap revision among head and neck cancer patients remains poorly
characterized. This study evaluates patients who underwent flap revision and
their surgical outcomes. Patients who underwent tumor extirpation with free flap
reconstruction were identified over a 5-year period. Elective flap revision was
defined as debulking or redraping of the original free flap for functional or
cosmetic reasons. Patient demographics, surgical indications, and outcomes were
reviewed. One hundred and eighty-six patients were identified, and 19 (10.2%)
underwent flap revision. Revision of oral cavity flaps (n = 9, 47.4%) was
performed to address excessive flap bulk compromising lip competence, speech,
swallowing, mastication, or placement of a dental prosthesis. Revision of flaps
resurfacing the face or neck (n = 10, 52.6%) was performed to address facial
ptosis after facial nerve sacrifice, facial asymmetry, or soft tissue redundancy.
Revisions were performed at an average of 7.3 months postoperatively and there
was no age or gender bias toward undergoing flap revision. Patients whose flap
skin paddles were used to resurface the facial or neck skin were significantly
more likely to undergo elective revision than patients with an external paddle
designed for flap monitoring (p < 0.01). We identified a 10% elective revision
rate for head and neck free flaps in cancer patients, approximately half of which
were performed to improve oral cavity function and half of which were performed
to address facial ptosis or asymmetry. While there was no age or gender
preference for flap revision, extensive facial or neck resurfacing was
significantly associated with eventual flap revision.
PMID- 26419864
TI - Paving the COWpath: Learning and visualizing clinical pathways from electronic
health record data.
AB - OBJECTIVE: Clinical pathways translate best available evidence into practice,
indicating the most widely applicable order of treatment interventions for
particular treatment goals. We propose a practice-based clinical pathway
development process and a data-driven methodology for extracting common clinical
pathways from electronic health record (EHR) data that is patient-centered,
consistent with clinical workflow, and facilitates evidence-based care. MATERIALS
AND METHODS: Visit data of 1,576 chronic kidney disease (CKD) patients who
developed acute kidney injury (AKI) from 2009 to 2013 are extracted from the EHR.
We model each patient's multi-dimensional clinical records into one-dimensional
sequences using novel constructs designed to capture information on each visit's
purpose, procedures, medications and diagnoses. Analysis and clustering on visit
sequences identify distinct types of patient subgroups. Characterizing visit
sequences as Markov chains, significant transitions are extracted and visualized
into clinical pathways across subgroups. RESULTS: We identified 31 patient
subgroups whose extracted clinical pathways provide insights on how patients'
conditions and medication prescriptions may progress over time. We identify
pathways that show typical disease progression, practices that are consistent
with guidelines, and sustainable improvements in patients' health conditions.
Visualization of pathways depicts the likelihood and direction of disease
progression under varied contexts. DISCUSSION AND CONCLUSIONS: Accuracy of EHR
data and diversity in patients' conditions and practice patterns are critical
challenges in learning insightful practice-based clinical pathways. Learning and
visualizing clinical pathways from actual practice data captured in the EHR may
facilitate efficient practice review by healthcare providers and support patient
engagement in shared decision making.
PMID- 26419865
TI - Evolvability Is an Evolved Ability: The Coding Concept as the Arch-Unit of
Natural Selection.
AB - Physical processes that characterize living matter are qualitatively distinct in
that they involve encoding and transfer of specific types of information. Such
information plays an active part in the control of events that are ultimately
linked to the capacity of the system to persist and multiply. This algorithmicity
of life is a key prerequisite for its Darwinian evolution, driven by natural
selection acting upon stochastically arising variations of the encoded
information. The concept of evolvability attempts to define the total capacity of
a system to evolve new encoded traits under appropriate conditions, i.e., the
accessible section of total morphological space. Since this is dependent on
previously evolved regulatory networks that govern information flow in the
system, evolvability itself may be regarded as an evolved ability. The way
information is physically written, read and modified in living cells (the "coding
concept") has not changed substantially during the whole history of the Earth's
biosphere. This biosphere, be it alone or one of many, is, accordingly, itself a
product of natural selection, since the overall evolvability conferred by its
coding concept (nucleic acids as information carriers with the "rulebook of
meanings" provided by codons, as well as all the subsystems that regulate various
conditional information-reading modes) certainly played a key role in enabling
this biosphere to survive up to the present, through alterations of planetary
conditions, including at least five catastrophic events linked to major mass
extinctions. We submit that, whatever the actual prebiotic physical and chemical
processes may have been on our home planet, or may, in principle, occur at some
time and place in the Universe, a particular coding concept, with its respective
potential to give rise to a biosphere, or class of biospheres, of a certain
evolvability, may itself be regarded as a unit (indeed the arch-unit) of natural
selection.
PMID- 26419871
TI - Outcome of Burns Treated With Autologous Cultured Proliferating Epidermal Cells:
A Prospective Randomized Multicenter Intrapatient Comparative Trial.
AB - Standard treatment for large burns is transplantation with meshed split skin
autografts (SSGs). A disadvantage of this treatment is that healing is
accompanied by scar formation. Application of autologous epidermal cells
(keratinocytes and melanocytes) may be a suitable therapeutic alternative, since
this may enhance wound closure and improve scar quality. A prospective,
multicenter randomized clinical trial was performed in 40 adult patients with
acute full thickness burns. On two comparable wound areas, conventional treatment
with SSGs was compared to an experimental treatment consisting of SSGs in
combination with cultured autologous epidermal cells (ECs) seeded in a collagen
carrier. The primary outcome measure was wound closure after 5-7 days. Secondary
outcomes were safety aspects and scar quality measured by graft take, scar score
(POSAS), skin colorimeter (DermaSpectrometer) and elasticity (Cutometer). Wound
epithelialization after 5-7 days was significantly better for the experimental
treatment (71%) compared to the standard treatment (67%) (p = 0.034, Wilcoxon),
whereas the take rates of the grafts were similar. No related adverse events were
recorded. Scar quality was evaluated at 3 (n = 33) and 12 (n = 28) months. The
POSAS of the observer after 3 and 12 months and of the patient after 12 months
were significantly better for the experimental area. Improvements between 12% and
23% (p <= 0.010, Wilcoxon) were detected for redness, pigmentation, thickness,
relief, and pliability. Melanin index at 3 and 12 months and erythema index at 12
months were closer to normal skin for the experimental treatment than for
conventional treatment (p <= 0.025 paired samples t-test). Skin elasticity showed
significantly higher elasticity (p = 0.030) in the experimental area at 3 months
follow-up. We showed a safe application and significant improvements of wound
healing and scar quality in burn patients after treatment with ECs versus SSGs
only. The relevance of cultured autologous cells in treatment of extensive burns
is supported by our current findings.
PMID- 26419872
TI - Newly graduated nurses' occupational commitment and its associations with
professional competence and work-related factors.
AB - AIMS AND OBJECTIVES: To explore newly graduated nurses' occupational commitment
and its associations with their self-assessed professional competence and other
work-related factors. BACKGROUND: As a factor affecting nurse turnover, newly
graduated nurses' occupational commitment and its associations with work-related
factors needs exploring to retain adequate workforce. Nurses' commitment has
mainly been studied as organisational commitment, but newly graduated nurses'
occupational commitment and its association with work-related factors needs
further studying. DESIGN: This study used descriptive, cross-sectional,
correlation design. METHODS: A convenience sample of 318 newly graduated nurses
in Finland participated responding to an electronic questionnaire. Statistical
software, NCSS version 9, was used in data analysis. Frequencies, percentages,
ranges, means and standard deviations summarised the data. Multivariate Analyses
of Variance estimated associations between occupational commitment and work
related variables. IBM SPSS Amos version 22 estimated the model fit of
Occupational Commitment Scale and Nurse Competence Scale. RESULTS: Newly
graduated nurses' occupational commitment was good, affective commitment reaching
the highest mean score. There was a significant difference between the nurse
groups in favour of nurses at higher competence levels in all subscales except in
limited alternatives occupational commitment. Multivariate analyses revealed
significant associations between subscales of commitment and competence, turnover
intentions, job satisfaction, earlier professional education and work sector,
competence counting only through affective dimension. CONCLUSION: The association
between occupational commitment and low turnover intentions and satisfaction with
nursing occupation was strong. Higher general competence indicated higher overall
occupational commitment. RELEVANCE TO CLINICAL PRACTICE: Managers' recognition of
the influence of all dimensions of occupational commitment in newly graduated
nurses' professional development is important. Follow-up studies of newly
graduated nurses' commitment, its relationship with quality care, managers' role
in enhancing commitment and evaluation of the impact of interventions on
improving commitment need further studying.
PMID- 26419873
TI - Robustness of cell cycle control and flexible orders of signaling events.
AB - The highly robust control of cell cycles in eukaryotes enables cells to undergo
strictly ordered G1/S/G2/M phases and respond adaptively to regulatory signals;
however the nature of the robustness remains obscure. Specifically, it is unclear
whether events of signaling should be strictly ordered and whether some events
are more robust than others. To quantitatively address the two questions, we have
developed a novel cell cycle model upon experimental observations. It contains
positive and negative E2F proteins and two Cdk inhibitors, and is parameterized,
for the first time, to generate not only oscillating protein concentrations but
also periodic signaling events. Events and their orders reconstructed under
varied conditions indicate that proteolysis of cyclins and Cdk complexes by APC
and Skp2 occurs highly robustly in a strict order, but many other events are
either dispensable or can occur in flexible orders. These results suggest that
strictly ordered proteolytic events are essential for irreversible cell cycle
progression and the robustness of cell cycles copes with flexible orders of
signaling events, and unveil a new and important dimension to the robustness of
cell cycle control in particular and to biological signaling in general.
PMID- 26419874
TI - Relationship between serum cortisol levels and some physiological parameters
following reining training session in horse.
AB - The changes of cortisol, red blood cells (RBC), hemoglobin (Hb), hematocrit
(Hct), heart rate (HR), respiratory rate (RR) and rectal temperature (RT) were
evaluated after a reining training session in eight Quarter Horses. All
parameters were measured before exercise (T0), immediately after exercise (T1), 1
h after exercise (T2), 2 h after exercise (T3) and 24 h after exercise (T4). One
way analysis of variance (ANOVA) for repeated measures, followed Bonferroni's
post hoc test, showed a significant effect of the reining training session (P <
0.0001) on cortisol, RBC, Hb, Hct, HR, RR and RT. Simple linear regression
analysis showed the positive correlation (P < 0.05) between cortisol changes and
variations of studied parameters in T1, T3 and T4. Exercise-induced cortisol
concentrations reflect the physiological response of reining training, suggesting
that the changes observed are useful to assess the performance in reining horses
and their reining training adaptability.
PMID- 26419875
TI - High-Frequency Variation of Purine Biosynthesis Genes Is a Mechanism of Success
in Campylobacter jejuni.
AB - Phenotypic variation is prevalent in the zoonotic pathogen Campylobacter jejuni,
the leading agent of enterocolitis in the developed world. Heterogeneity enhances
the survival and adaptive malleability of bacterial populations because variable
phenotypes may allow some cells to be protected against future stress. Exposure
to hyperosmotic stress previously revealed prevalent differences in growth
between C. jejuni strain 81-176 colonies due to resistant or sensitive
phenotypes, and these isolated colonies continued to produce progeny with
differential phenotypes. In this study, whole-genome sequencing of isolated
colonies identified allelic variants of two purine biosynthesis genes, purF and
apt, encoding phosphoribosyltransferases that utilize a shared substrate. Genetic
analyses determined that purF was essential for fitness, while apt was critical.
Traditional and high-depth amplicon-sequencing analyses confirmed extensive
intrapopulation genetic variation of purF and apt that resulted in viable strains
bearing alleles with in-frame insertion duplications, deletions, or missense
polymorphisms. Different purF and apt alleles were associated with various stress
survival capabilities under several niche-relevant conditions and contributed to
differential intracellular survival in an epithelial cell infection model.
Amplicon sequencing revealed that intracellular survival selected for stress-fit
purF and apt alleles, as did exposure to oxygen and hyperosmotic stress. Putative
protein recognition direct repeat sequences were identified in purF and apt, and
a DNA-protein affinity screen captured a predicted exonuclease that promoted the
global spontaneous mutation rate. This work illustrates the adaptive properties
of high-frequency genetic variation in two housekeeping genes, which influences
C. jejuni survival under stress and promotes its success as a pathogen.
IMPORTANCE: C. jejuni is an important cause of bacterial diarrheal illness.
Bacterial populations have many strategies for stress survival, but phenotypic
variation due to genetic diversity has a powerful advantage: no matter how swift
the change in environment, a fraction of the population already expresses the
survival trait. Nonclonality is thus increasingly viewed as a mechanism of
population success. Our previous work identified prominent resistant/sensitive
colonial variation in C. jejuni bacteria in response to hyperosmotic stress; in
the work presented here, we attribute that to high-frequency genetic variation in
two purine biosynthesis genes, purF and apt. We demonstrated selective pressure
for nonlethal mutant alleles of both genes, showed that single-cell variants had
the capacity to give rise to diverse purF and apt populations, and determined
that stress exposure selected for desirable alleles. Thus, a novel C. jejuni
adaptive strategy was identified, which was, unusually, reliant on prevalent
genetic variation in two housekeeping genes.
PMID- 26419876
TI - Ontogenetic Differences in Dietary Fat Influence Microbiota Assembly in the
Zebrafish Gut.
AB - Gut microbiota influence the development and physiology of their animal hosts,
and these effects are determined in part by the composition of these microbial
communities. Gut microbiota composition can be affected by introduction of
microbes from the environment, changes in the gut habitat during development, and
acute dietary alterations. However, little is known about the relationship
between gut and environmental microbiotas or about how host development and
dietary differences during development impact the assembly of gut microbiota. We
sought to explore these relationships using zebrafish, an ideal model because
they are constantly immersed in a defined environment and can be fed the same
diet for their entire lives. We conducted a cross-sectional study in zebrafish
raised on a high-fat, control, or low-fat diet and used bacterial 16S rRNA gene
sequencing to survey microbial communities in the gut and external environment at
different developmental ages. Gut and environmental microbiota compositions
rapidly diverged following the initiation of feeding and became increasingly
different as zebrafish grew under conditions of a constant diet. Different
dietary fat levels were associated with distinct gut microbiota compositions at
different ages. In addition to alterations in individual bacterial taxa, we
identified putative assemblages of bacterial lineages that covaried in abundance
as a function of age, diet, and location. These results reveal dynamic
relationships between dietary fat levels and the microbial communities residing
in the intestine and the surrounding environment during ontogenesis. IMPORTANCE:
The ability of gut microbiota to influence host health is determined in part by
their composition. However, little is known about the relationship between gut
and environmental microbiotas or about how ontogenetic differences in dietary fat
impact gut microbiota composition. We addressed these gaps in knowledge using
zebrafish, an ideal model organism because their environment can be thoroughly
sampled and they can be fed the same diet for their entire lives. We found that
microbial communities in the gut changed as zebrafish aged under conditions of a
constant diet and became increasingly different from microbial communities in
their surrounding environment. Further, we observed that the amount of fat in the
diet had distinct age-specific effects on gut community assembly. These results
reveal the complex relationships between microbial communities residing in the
intestine and those in the surrounding environment and show that these
relationships are shaped by dietary fat throughout the life of animal hosts.
PMID- 26419877
TI - Unique Organization of Extracellular Amylases into Amylosomes in the Resistant
Starch-Utilizing Human Colonic Firmicutes Bacterium Ruminococcus bromii.
AB - Ruminococcus bromii is a dominant member of the human gut microbiota that plays a
key role in releasing energy from dietary starches that escape digestion by host
enzymes via its exceptional activity against particulate "resistant" starches.
Genomic analysis of R. bromii shows that it is highly specialized, with 15 of its
21 glycoside hydrolases belonging to one family (GH13). We found that amylase
activity in R. bromii is expressed constitutively, with the activity seen during
growth with fructose as an energy source being similar to that seen with starch
as an energy source. Six GH13 amylases that carry signal peptides were detected
by proteomic analysis in R. bromii cultures. Four of these enzymes are among 26
R. bromii proteins predicted to carry dockerin modules, with one, Amy4, also
carrying a cohesin module. Since cohesin-dockerin interactions are known to
mediate the formation of protein complexes in cellulolytic ruminococci, the
binding interactions of four cohesins and 11 dockerins from R. bromii were
investigated after overexpressing them as recombinant fusion proteins. Dockerins
possessed by the enzymes Amy4 and Amy9 are predicted to bind a cohesin present in
protein scaffoldin 2 (Sca2), which resembles the ScaE cell wall-anchoring protein
of a cellulolytic relative, R. flavefaciens. Further complexes are predicted
between the dockerin-carrying amylases Amy4, Amy9, Amy10, and Amy12 and two other
cohesin-carrying proteins, while Amy4 has the ability to autoaggregate, as its
dockerin can recognize its own cohesin. This organization of starch-degrading
enzymes is unprecedented and provides the first example of cohesin-dockerin
interactions being involved in an amylolytic system, which we refer to as an
"amylosome." IMPORTANCE: Fermentation of dietary nondigestible carbohydrates by
the human colonic microbiota supplies much of the energy that supports microbial
growth in the intestine. This activity has important consequences for health via
modulation of microbiota composition and the physiological and nutritional
effects of microbial metabolites, including the supply of energy to the host from
short-chain fatty acids. Recent evidence indicates that certain human colonic
bacteria play keystone roles in degrading nondigestible substrates, with the
dominant but little-studied species Ruminococcus bromii displaying an exceptional
ability to degrade dietary resistant starches (i.e., dietary starches that escape
digestion by host enzymes in the upper gastrointestinal tract because of
protection provided by other polymers, particle structure, retrogradation, or
chemical cross-linking). In this report, we reveal the unique organization of the
amylolytic enzyme system of R. bromii that involves cohesin-dockerin interactions
between component proteins. While dockerins and cohesins are fundamental to the
organization of cellulosomal enzyme systems of cellulolytic ruminococci, their
contribution to organization of amylases has not previously been recognized and
may help to explain the starch-degrading abilities of R. bromii.
PMID- 26419878
TI - Reply to "Statins may decrease the Fatality Rate of MERS Infection".
PMID- 26419879
TI - A Phase-Variable Surface Layer from the Gut Symbiont Bacteroides
thetaiotaomicron.
AB - The capsule from Bacteroides, a common gut symbiont, has long been a model system
for studying the molecular mechanisms of host-symbiont interactions. The
Bacteroides capsule is thought to consist of an array of phase-variable
polysaccharides that give rise to subpopulations with distinct cell surface
structures. Here, we report the serendipitous discovery of a previously unknown
surface structure in Bacteroides thetaiotaomicron: a surface layer composed of a
protein of unknown function, BT1927. BT1927, which is expressed in a phase
variable manner by ~1:1,000 cells in a wild-type culture, forms a hexagonally
tessellated surface layer. The BT1927-expressing subpopulation is profoundly
resistant to complement-mediated killing, due in part to the BT1927-mediated
blockade of C3b deposition. Our results show that the Bacteroides surface
structure is capable of a far greater degree of structural variation than
previously known, and they suggest that structural variation within a Bacteroides
species is important for productive gut colonization. IMPORTANCE: Many bacterial
species elaborate a capsule, a structure that resides outside the cell wall and
mediates microbe-microbe and microbe-host interactions. Species of Bacteroides,
the most abundant genus in the human gut, produce a capsule that consists of an
array of polysaccharides, some of which are known to mediate interactions with
the host immune system. Here, we report the discovery of a previously unknown
surface structure in Bacteroides thetaiotaomicron. We show that this protein
based structure is expressed by a subset of cells in a population and protects
Bacteroides from killing by complement, a component of the innate immune system.
This novel surface layer protein is conserved across many species of the genus
Bacteroides, suggesting an important role in colonization and host immune
modulation.
PMID- 26419880
TI - Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals
Cryptococcal Determinants of Virulence and Central Nervous System Invasion.
AB - The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad
range of hosts, from invertebrates like amoebas and nematodes to standard
vertebrate models such as mice and rabbits. Here we have taken advantage of a
zebrafish model to investigate host-pathogen interactions of Cryptococcus with
the zebrafish innate immune system, which shares a highly conserved framework
with that of mammals. Through live-imaging observations and genetic knockdown, we
establish that macrophages are the primary immune cells responsible for
responding to and containing acute cryptococcal infections. By interrogating
survival and cryptococcal burden following infection with a panel of Cryptococcus
mutants, we find that virulence factors initially identified as important in
causing disease in mice are also necessary for pathogenesis in zebrafish larvae.
Live imaging of the cranial blood vessels of infected larvae reveals that C.
neoformans is able to penetrate the zebrafish brain following intravenous
infection. By studying a C. neoformans FNX1 gene mutant, we find that blood-brain
barrier invasion is dependent on a known cryptococcal invasion-promoting pathway
previously identified in a murine model of central nervous system invasion. The
zebrafish-C. neoformans platform provides a visually and genetically accessible
vertebrate model system for cryptococcal pathogenesis with many of the advantages
of small invertebrates. This model is well suited for higher-throughput screening
of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals,
and use in the evaluation of therapeutic agents. IMPORTANCE: Cryptococcus
neoformans is an important opportunistic pathogen that is estimated to be
responsible for more than 600,000 deaths worldwide annually. Existing mammalian
models of cryptococcal pathogenesis are costly, and the analysis of important
pathogenic processes such as meningitis is laborious and remains a challenge to
visualize. Conversely, although invertebrate models of cryptococcal infection
allow high-throughput assays, they fail to replicate the anatomical complexity
found in vertebrates and, specifically, cryptococcal stages of disease. Here we
have utilized larval zebrafish as a platform that overcomes many of these
limitations. We demonstrate that the pathogenesis of C. neoformans infection in
zebrafish involves factors identical to those in mammalian and invertebrate
infections. We then utilize the live-imaging capacity of zebrafish larvae to
follow the progression of cryptococcal infection in real time and establish a
relevant model of the critical central nervous system infection phase of disease
in a nonmammalian model.
PMID- 26419881
TI - The 1977 H1N1 Influenza Virus Reemergence Demonstrated Gain-of-Function Hazards.
PMID- 26419883
TI - Reply to "The 1977 H1N1 Influenza Virus Reemergence Demonstrated Gain-of-Function
Hazards".
PMID- 26419882
TI - Insufficient Acidification of Autophagosomes Facilitates Group A Streptococcus
Survival and Growth in Endothelial Cells.
AB - Group A streptococcus (GAS) is an important human pathogen, and its invasion via
blood vessels is critically important in serious events such as bacteremia or
multiorgan failure. Although GAS was identified as an extracellular bacterium,
the internalization of GAS into nonphagocytic cells may provide a strategy to
escape from immune surveillance and antibiotic killing. However, GAS has also
been reported to induce autophagy and is efficiently killed within lysosome-fused
autophagosomes in epithelial cells. In this study, we show that GAS can replicate
in endothelial cells and that streptolysin O is required for GAS growth.
Bacterial replication can be suppressed by altering GAS gene expression in an
acidic medium before internalization into endothelial cells. The inhibitory
effect on GAS replication can be reversed by treatment with bafilomycin A1, a
specific inhibitor of vacuolar-type H(+)-ATPase. Compared with epithelial cells
in which acidification causes autophagy-mediated clearance of GAS, there was a
defect in acidification of GAS-containing vesicles in endothelial cells.
Consequently, endothelial cells fail to maintain low pH in GAS-containing
autophagosomes, thereby permitting GAS replication inside LAMP-1- and LC3
positive vesicles. Furthermore, treatment of epithelial cells with bafilomycin A1
resulted in defective GAS clearance by autophagy, with subsequent bacterial
growth intracellularly. Therefore, low pH is a key factor for autophagy-mediated
suppression of GAS growth inside epithelial cells, while defective acidification
of GAS-containing vesicles results in bacterial growth in endothelial cells.
IMPORTANCE: Previous reports showed that GAS can induce autophagy and is
efficiently killed within lysosome-fused autophagosomes in epithelial cells. In
endothelial cells, in contrast, induction of autophagy is not sufficient for GAS
killing. In this study, we provide the first evidence that low pH is required to
prevent intracellular growth of GAS in epithelial cells and that this mechanism
is defective in endothelial cells. Treatment of GAS with low pH altered GAS
growth rate and gene expression of virulence factors and resulted in enhanced
susceptibility of GAS to intracellular lysosomal killing. Our findings reveal the
existence of different mechanisms of host defense against GAS invasion between
epithelial and endothelial cells.
PMID- 26419884
TI - ABA signalling is fine-tuned by antagonistic HAB1 variants.
AB - Group A protein type 2C phosphatases (PP2Cs) are negative regulators of abscisic
acid (ABA) signalling and plant adaptation to stress. However, our knowledge of
the regulation of PP2C activity is limited. Here we report that the PP2C HAB1
undergoes alternative splicing to produce two splice variants, which encode
HAB1.1 and HAB1.2, that play opposing roles in ABA-mediated seed germination and
ABA-mediated post-germination developmental arrest. HAB1.2 is predominately
formed in the presence of ABA and prevents seed germination and post-germinative
growth. HAB1.2 interacts with OST1, but cannot inhibit OST1 kinase activity;
thus, it functions as a positive regulator of ABA signalling. We also identified
an RNA-recognition motif-containing protein, RBM25, as a potential regulator of
HAB1 alternative splicing and molecular diversity. Our results reveal a mechanism
for turning ABA signalling on and off and for plant adaptation to abiotic stress.
PMID- 26419885
TI - Bio-inspired electron-delivering system for reductive activation of dioxygen at
metal centres towards artificial flavoenzymes.
AB - Development of artificial systems, capable of delivering electrons to metal-based
catalysts for the reductive activation of dioxygen, has been proven very
difficult for decades, constituting a major scientific lock for the elaboration
of environmentally friendly oxidation processes. Here we demonstrate that the
incorporation of a flavin mononucleotide (FMN) in a water-soluble polymer,
bearing a locally hydrophobic microenvironment, allows the efficient reduction of
the FMN by NADH. This supramolecular entity is then capable of catalysing a very
fast single-electron reduction of manganese(III) porphyrin by splitting the
electron pair issued from NADH. This is fully reminiscent of the activity of
natural reductases such as the cytochrome P450 reductases with kinetic
parameters, which are three orders of magnitude faster compared with other
artificial systems. Finally, we show as a proof of concept that the reduced
manganese porphyrin activates dioxygen and catalyses the oxidation of organic
substrates in water.
PMID- 26419886
TI - How does cigarette smoking cause acute pancreatitis?
AB - INTRODUCTION: Acute Pancreatitis (AP) is an emerging health problem world-wide
and it is a major cause of admissions for gastrointestinal disease in many
countries. Amongst the more common causes (alcohol and gallstones), recent
evidence has emerged indicating that smoking is an independent risk factor for
AP. However, the mechanisms involved in smoking-induced AP have not been
completely elucidated. This review puts together all the published evidence in
literature to present the clinical and laboratory evidence relating smoking to
the causation of AP. DISCUSSION: The two main metabolites from cigarette smoke,
namely nicotine and NNK are able to induce functional and histological changes
within the pancreas consistent with AP. The major mechanisms involved include
their action on acinar cells and zymogen secretion through pathways involving CCK
and the nicotinic preganglionic receptors. Effects on the pancreatic
microvasculature may be mediated through the nitric oxide pathway. There is
indirect evidence to suggest that nicotine and acrolein may lead to CFTR
dysfunction thereby influencing ductal secretion. However, direct evidence for
this effect is needed. The effect of cigarette smoke metabolites on stellate
cells and the islets warrants further investigation in the context of
pathogenesis of AP. CONCLUSION: Using a step-wise approach, the review revisits
the effects of the various metabolites of cigarette smoke on the constituents of
the pancreas (exocrine, endocrine, neurohormonal, stellate cells, ductal system)
and highlights their proven, and potential, mechanisms in triggering off an
attack of AP.
PMID- 26419887
TI - Alcohol use initiation is associated with changes in personality trait
trajectories from early adolescence to young adulthood.
AB - BACKGROUND: Recent work has demonstrated the codevelopment of personality traits
and alcohol use characteristics from early adolescence to young adulthood. Few
studies, however, have tested whether alcohol use initiation impacts trajectories
of personality over this time period. We examined the effect of alcohol use
initiation on personality development from early adolescence to young adulthood.
METHODS: Participants were male (nmen = 2,350) and female (nwomen = 2,618) twins
and adoptees from 3 community-based longitudinal studies conducted at the
Minnesota Center for Twin and Family Research. Data on personality traits of
Positive Emotionality (PEM; Well-being), Negative Emotionality (NEM; Stress
Reaction, Alienation, and Aggression), and Constraint (CON; Control and Harm
Avoidance)-assessed via the Multidimensional Personality Questionnaire (MPQ)-and
age of first drink were collected for up to 4 waves spanning ages 10 to 32.
RESULTS: Alcohol use initiation was associated with significant decreases in
levels of Well-being and CON traits, most notably Control; and significant
increases in levels of all NEM traits, particularly Aggression. In general, the
effects of alcohol use initiation on personality traits were moderated by gender
and enhanced among those with earlier age of first drink. CONCLUSIONS: From early
adolescence to young adulthood, alcohol use initiation predicts deviations from
normative patterns of personality maturation. Such findings offer a potential
mechanism underlying the codevelopment of personality traits and alcohol use
characteristics during this formative period of development.
PMID- 26419888
TI - Osteogenic Differentiation Evaluation of an Engineered Extracellular Matrix Based
Tissue Sheet for Potential Periosteum Replacement.
AB - Due to the indispensable role of periosteum in bone defect healing and
regeneration, a promising method to enhance osteogenesis of bone grafts by using
an engineered biomimetic periosteum would be highly beneficial. The stromal
microenvironment of periosteum is composed of various highly organized
extracellular matrix (ECM) fibers, so an aligned natural ECM sheet, derived from
the human dermal fibroblast cell sheet, may be advantageous when applied for
artificial periosteum fabrication. Human mesenchymal stem cells (hMSCs) have been
used to replace the osteoprogenitor cell population in native periosteum due to
hMSCs' great osteogenic potential and fast in vitro expansion capacity. The
objective of this work is to investigate if the natural ECM sheet and the
substrate alignment can promote in vitro osteogenesis of hMSCs. The conventional
cell culture substrates collagen I-coated polydimethylsiloxane (PDMS) and tissue
culture plastic (TCP) were used as controls. It was found that the ECM sheet
significantly increased alkaline phosphatase activity and calcium deposition. The
enhanced osteogenic potential was further confirmed by increased bone-specific
gene expression. The ECM sheet can bind significantly higher amounts of growth
factors including ANG-1, TGF-beta1, bFGF, and VEGF, as well as calcium phosphate
nanoparticles, which contributed to high osteogenesis of the hMSCs on ECM sheet.
However, the alignment of the substrates did not show significant influence on
osteogenic activity and growth factor binding. These results demonstrated the
great potential of hMSC-seeded ECM sheet as a biomimetic periosteum to improve
critical sized bone regeneration.
PMID- 26419889
TI - Germ plasm localisation of the HELICc of Vasa in Drosophila: analysis of domain
sufficiency and amino acids critical for localisation.
AB - Formation of the germ plasm drives germline specification in Drosophila and some
other insects such as aphids. Identification of the DEAD-box protein Vasa (Vas)
as a conserved germline marker in flies and aphids suggests that they share
common components for assembling the germ plasm. However, to which extent the
assembly order is conserved and the correlation between functions and sequences
of Vas remain unclear. Ectopic expression of the pea aphid Vas (ApVas1) in
Drosophila did not drive its localisation to the germ plasm, but ApVas1 with a
replaced C-terminal domain (HELICc) of Drosophila Vas (DmVas) became germ-plasm
restricted. We found that HELICc itself, through the interaction with Oskar
(Osk), was sufficient for germ-plasm localisation. Similarly, HELICc of the
grasshopper Vas could be recruited to the germ plasm in Drosophila. Nonetheless,
germ-plasm localisation was not seen in the Drosophila oocytes expressing HELICcs
of Vas orthologues from aphids, crickets, and mice. We further identified that
glutamine (Gln) 527 within HELICc of DmVas was critical for localisation, and its
corresponding residue could also be detected in grasshopper Vas yet missing in
the other three species. This suggests that Gln527 is a direct target of Osk or
critical to the maintenance of HELICc conformation.
PMID- 26419890
TI - Social cognition and the cerebellum: A meta-analytic connectivity analysis.
AB - This meta-analytic connectivity modeling (MACM) study explores the functional
connectivity of the cerebellum with the cerebrum in social cognitive processes.
In a recent meta-analysis, Van Overwalle, Baetens, Marien, and Vandekerckhove
(2014) documented that the cerebellum is implicated in social processes of "body"
reading (mirroring; e.g., understanding other persons' intentions from observing
their movements) and "mind" reading (mentalizing, e.g., inferring other persons'
beliefs, intentions or personality traits, reconstructing persons' past, future,
or hypothetical events). In a recent functional connectivity study, Buckner et
al. (2011) offered a novel parcellation of cerebellar topography that
substantially overlaps with the cerebellar meta-analytic findings of Van
Overwalle et al. (2014). This overlap suggests that the involvement of the
cerebellum in social reasoning depends on its functional connectivity with the
cerebrum. To test this hypothesis, we explored the meta-analytic co-activations
as indices of functional connectivity between the cerebellum and the cerebrum
during social cognition. The MACM results confirm substantial and distinct
connectivity with respect to the functions of (a) action understanding ("body"
reading) and (b) mentalizing ("mind" reading). The consistent and strong
connectivity findings of this analysis suggest that cerebellar activity during
social judgments reflects distinct mirroring and mentalizing functionality, and
that these cerebellar functions are connected with corresponding functional
networks in the cerebrum.
PMID- 26419891
TI - Unravelling polar lipids dynamics during embryonic development of two sympatric
brachyuran crabs (Carcinus maenas and Necora puber) using lipidomics.
AB - Embryogenesis is an important stage of marine invertebrates with bi-phasic life
cycles, as it conditions their larval and adult life. Throughout embryogenesis,
phospholipids (PL) play a key role as an energy source, as well as constituents
of biological membranes. However, the dynamics of PL during embryogenesis in
marine invertebrates is still poorly studied. The present work used a lipidomic
approach to determine how polar lipid profiles shift during embryogenesis in two
sympatric estuarine crabs, Carcinus maenas and Necora puber. The combination of
thin layer chromatography, liquid chromatography-mass spectrometry and gas
chromatography-mass spectrometry allowed us to achieve an unprecedented
resolution on PL classes and molecular species present on newly extruded embryos
(stage 1) and those near hatching (stage 3). Embryogenesis proved to be a dynamic
process, with four PL classes being recorded in stage 1 embryos (68 molecular
species in total) and seven PL classes at stage 3 embryos (98 molecular species
in total). The low interspecific difference recorded in the lipidomic profiles of
stage 1 embryos appears to indicate the existence of similar maternal investment.
The same pattern was recorded for stage 3 embryos revealing a similar catabolism
of embryonic resources during incubation for both crab species.
PMID- 26419892
TI - Accounting for patient size in the optimization of dose and image quality of
pelvis cone beam CT protocols on the Varian OBI system.
AB - OBJECTIVE: The purpose of this study was to develop size-based radiotherapy
kilovoltage cone beam CT (CBCT) protocols for the pelvis. METHODS: Image noise
was measured in an elliptical phantom of varying size for a range of exposure
factors. Based on a previously defined "small pelvis" reference patient and CBCT
protocol, appropriate exposure factors for small, medium, large and extra-large
patients were derived which approximate the image noise behaviour observed on a
Philips CT scanner (Philips Medical Systems, Best, Netherlands) with automatic
exposure control (AEC). Selection criteria, based on maximum tube current-time
product per rotation selected during the radiotherapy treatment planning scan,
were derived based on an audit of patient size. RESULTS: It has been demonstrated
that 110 kVp yields acceptable image noise for reduced patient dose in pelvic
CBCT scans of small, medium and large patients, when compared with manufacturer's
default settings (125 kVp). Conversely, extra-large patients require increased
exposure factors to give acceptable images. 57% of patients in the local
population now receive much lower radiation doses, whereas 13% require higher
doses (but now yield acceptable images). CONCLUSION: The implementation of size
based exposure protocols has significantly reduced radiation dose to the majority
of patients with no negative impact on image quality. Increased doses are
required on the largest patients to give adequate image quality. ADVANCES IN
KNOWLEDGE: The development of size-based CBCT protocols that use the planning CT
scan (with AEC) to determine which protocol is appropriate ensures adequate image
quality whilst minimizing patient radiation dose.
PMID- 26419893
TI - Racemic cobalt phosphonates incorporating flexible bis(imidazole) co-ligands.
AB - By incorporating flexible bis(imidazol-1-ylmethyl)benzene (bix) co-ligands, four
new racemic cobalt phosphonates with formulae Co3(3-ppap)2(1,4-bix)2(H2O)4.4H2O
(1), Co3(3-ppap)2(1,3-bix)2(H2O)4.5H2O (2), Co3(3-ppap)2(1,2-bix)2(H2O)4.4H2O (3)
and Co3(ppa)2(1,2-bix)2.4H2O (4) are isolated, where 3-ppapH3 represents 3-phenyl
3-((phosphonomethyl)amino)propanoic acid and ppaH3 is 2-phenyl-2
(phosphonomethylamino)acetic acid. Compounds 1-3 crystallize in the monoclinic
space group P21/c and show two-dimensional structures in which the Co3(3-ppap)2
chains are bridged by 1,4-bix, 1,3-bix and 1,2-bix ligands in trans-modes,
respectively. Within the chain, a racemic dimer of Co2(3-ppap)2(2-) is found,
where the Co atoms are doubly bridged by O-P-O units from the (S)- and (R)-3
ppap(3-) ligands. The dimers are connected by another crystallographically
independent Co atom through O-P-O linkages to form an infinite racemic chain. The
packing modes of the layers in 1-3 are quite different, however, which are ABAB
in the cases of 1 and 3 while ABCDABCD in the case of 2, attributed to the
positional isomerism of the bix co-ligands. Compound 4 displays a chain structure
in which the 1,2-bix bridges the Co atoms in cis-mode within the chain. Magnetic
properties are investigated for all compounds.
PMID- 26419895
TI - Validation of a German version of the International Hip Outcome Tool (G-iHOT33)
according to the COSMIN checklist: how much improvement is clinically relevant?
AB - PURPOSE: The evaluation of the subjective health-related quality of life is
especially for young, active patients with hip joint disorders important. The
MAHORN study group has recently developed the "International Hip Outcome Tool"
(iHOT33), a self-administered patient-reported outcome tool, which includes
questions on the patient's symptoms, functional and sports limitations as well as
social, emotional, and occupational limitations. The purpose of this study was to
adapt and validate a German version of the iHOT33 according to the COSMIN
checklist. METHODS: To validate the G-iHOT33, we conducted a prospective
multicenter cohort study on patients with hip disorders and a score >=4 on the
modified Tegner Activity Scale. The patients completed the G-iHOT33 questionnaire
twice at intervals of at least 2 weeks. In addition, we recorded the Hip Outcome
Score (HOS), a modified Tegner Activity Scale (TAS), the EuroQol-5D (EQ5-D), and
a subjective assessment of the limitations. Evaluation of psychometric properties
was conducted following the COSMIN checklist for validation of health status
measurement instruments. The methodical testing for reliability included internal
consistency, test-retest reliability, and measurement error. For testing of
validity, we analyzed construct validity, hypotheses testing, interpretability,
and responsiveness. RESULTS: Between December 2013 and December 2014, eighty
three consecutive patients completed both questionnaires and were available for
data analysis. Cronbach's alpha was 0.97 (95% CI 0.96, 0.99) confirming internal
consistency and test-retest reliability of the G-iHOT-33 was high with an ICC =
0.88 (95% CI 0.80, 0.99). All a priori hypotheses were confirmed, further, no
floor- or ceiling-effects occurred. The G-iHOT33 showed good responsiveness with
a minimal important change (MIC) of 10 points. CONCLUSIONS: The German
translation of the iHOT-33 (G-iHOT-33) is a viable tool for the evaluation of
active patients with a hip disorder. Following the complete COSMIN checklist, we
could prove that G-iHOT33 is a reliable, valid, and responsive PRO measurement
tool. We could show that the minimal important change, a change of health
condition the patient discerns is 10 points in the G-iHOT33 scale. This is the
first study providing results on psychometric properties of the iHOT33 subscales.
Level of evidence 1b validating cohort study.
PMID- 26419894
TI - Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune
activation.
AB - Chikungunya, "that which bends up" in the Makonde dialect, is an emerging global
health threat, with increasing incidence of neurological complications. Until
2013, Chikungunya infection had been largely restricted to East Africa and the
Indian Ocean, with cases within the USA reported to be from foreign travel.
However, in 2014, over 1 million suspected cases were reported in the Americas,
and a recently infected human could serve as an unwitting reservoir for the virus
resulting in an epidemic in the continental USA. Chikungunya infection is
increasingly being associated with neurological sequelae. In this study, we
sought to understand the role of astrocytes in the neuropathogenesis of
Chikungunya infection. Even after virus has been cleared form the circulation,
astrocytes were activated with regard to TLR2 expression. In addition, white
matter astrocytes were hypertrophic, with increased arbor volume in gray matter
astrocytes. Combined, these would alter the number and distribution of synapses
that each astrocyte would be capable of forming. These results provide the first
evidence that Chikungunya infection induces morphometric and innate immune
activation of astrocytes in vivo. Perturbed glia-neuron signaling could be a
major driving factor in the development of Chikungunya-associated neuropathology.
PMID- 26419896
TI - Double mobility cup total hip arthroplasty in patients at high risk for
dislocation: a single-center analysis.
AB - INTRODUCTION: Double mobility cup systems (DMCS) have gained increasing
acceptance, especially in patients at high risk for dislocation. The aim of this
investigation was to analyze the frequency and indications of the DMCS use in our
praxis and to evaluate dislocation and cup revision rates after a minimum follow
up of 2 years. MATERIALS AND METHODS: All patients implanted with a DMCS from May
2008 to August 2011 were identified from our institutional database of primary
and revision THA procedures. Patient demographics, including ASA score, were
recorded, along with details of the surgical procedures, indications for DMCS
use, and post-operative clinical course and any complications. Radiographs were
analyzed for implant positioning and radiological signs of loosening. RESULTS:
1046 primary THA were implanted, of these 39 (4 %) primary DMCS. Indications were
severe neuromuscular disease (SND) (14), hip abductor degeneration (HAD) (9),
cognitive dysfunction (CD) (8) and others. 345 revision THA were performed, of
these 50 (14 %) revision DMCS. Indications were recurrent dislocations (27),
multiple prior hip surgeries (13), HAD (5), CD (3) and others. Overall
dislocation rate was 2/89 (2 %); both in revision THA. Overall cup revision rate
was 5/89 (6 %): 3 septic, 1 periprosthetic acetabular fracture, 1
"intraprosthetic dissociation". 67 patients were available for the standardized
questionnaire at a median follow-up of 43 months (range 25-78). 19 patients were
not available for two-year follow-up: 17 died and two were lost to follow-up.
CONCLUSIONS: This study supports the use of DMCS constructs in primary and
revision hip arthroplasty for specific high-risk patients. We continue to
indicate DMCS in this patient group. We do caution against extending indications
for DMCS to lower risk patient groups due to unknown issues surrounding wear and
component longevity.
PMID- 26419897
TI - Arthroscopic Capsular Repair for Symptomatic Hip Instability After Previous Hip
Arthroscopic Surgery.
AB - BACKGROUND: Management of the hip capsule has been a topic of recent debate in
hip arthroscopic surgery. Postoperative instability after hip arthroscopic
surgery has been reported and can lead to poor outcomes. PURPOSE: To determine
the outcome of patients diagnosed with symptomatic instability after hip
arthroscopic surgery at a minimum of 12 months and 24 months after revision
surgery for capsular repair. STUDY DESIGN: Case series; Level of evidence, 4.
METHODS: In a cohort of approximately 1100 patients who underwent hip
arthroscopic surgery, 33 patients (33 hips) developed symptomatic instability
requiring a revision surgery. Two patients suffered anterior dislocations
following their initial surgery. Radiographs were reviewed to evaluate for
acetabular dysplasia. Three patients were lost to follow-up and 10 patients were
excluded as they were <1 year out from the revision surgery. A total of 20
patients (18 female, 2 male) completed a preoperative and postoperative modified
Harris Hip Score (mHHS) and Hip Outcome Score (HOS) at a minimum of 12 months.
Eleven of these patients had a minimum follow-up of 24 months. All patients
filled out a Likert scale of perceived improvement in physical ability at final
follow-up. RESULTS: The mean age of the patients was 29.7 years (range, 15.2-55.5
years). The mean lateral center-edge angle was 25 degrees , and the mean
acetabular index was 7 degrees before revision. All patients underwent
interportal capsulotomy during the index arthroscopic procedure. After their
index arthroscopic procedures, patients had minimal improvement at a mean of 19.1
months postoperatively on the mHHS (from 57.1 to 57.6; P = .423), HOS-Activities
of Daily Living (ADL) (from 62.7 to 66.4; P = .260), and HOS-Sports (from 42.0 to
39.1; P = .800). For the patients with a minimum 1-year follow-up after revision
surgery (n = 20; mean follow-up, 21.3 months), the mean mHHS (from 57.6
preoperatively to 85.8 at final follow-up; P < .001), HOS-ADL (from 66.4 to 85.7;
P < .001), and HOS-Sports (from 39.1 to 79.8; P < .001) all improved
significantly. The results were similar when looking at only the patients with a
minimum 2-year follow-up after revision surgery (n = 11; mean follow-up, 26.1
months); the mean mHHS (from 56.0 preoperatively to 91.5 at final follow-up; P =
.001), HOS-ADL (from 68.3 to 89.9; P = .009), and HOS-Sports (from 35.7 to 87.9;
P = .001) all improved significantly. When comparing patients with isolated
capsular repair to those with additional procedures performed, there were no
differences between the groups (all P > .05). At final follow-up, all but 1
patient had improved overall physical ability levels. CONCLUSION: Revision hip
arthroscopic surgery for capsular repair in patients with symptomatic instability
after hip arthroscopic surgery provides good functional outcomes at a minimum of
1 and 2 years postoperatively.
PMID- 26419898
TI - Host specificity in Sporisorium reilianum is determined by distinct mechanisms in
maize and sorghum.
AB - Smut fungi are biotrophic plant pathogens that exhibit a very narrow host range.
The smut fungus Sporisorium reilianum exists in two host-adapted formae
speciales: S. reilianum f. sp. reilianum (SRS), which causes head smut of
sorghum, and S. reilianum f. sp. zeae (SRZ), which induces disease on maize. It
is unknown why the two formae speciales cannot form spores on their respective
non-favoured hosts. By fungal DNA quantification and fluorescence microscopy of
stained plant samples, we followed the colonization behaviour of both SRS and SRZ
on sorghum and maize. Both formae speciales were able to penetrate and multiply
in the leaves of both hosts. In sorghum, the hyphae of SRS reached the apical
meristems, whereas the hyphae of SRZ did not. SRZ strongly induced several
defence responses in sorghum, such as the generation of H2 O2 , callose and
phytoalexins, whereas the hyphae of SRS did not. In maize, both SRS and SRZ were
able to spread through the plant to the apical meristem. Transcriptome analysis
of colonized maize leaves revealed more genes induced by SRZ than by SRS, with
many of them being involved in defence responses. Amongst the maize genes
specifically induced by SRS were 11 pentatricopeptide repeat proteins. Together
with the microscopic analysis, these data indicate that SRZ succumbs to plant
defence after sorghum penetration, whereas SRS proliferates in a relatively
undisturbed manner, but non-efficiently, on maize. This shows that host
specificity is determined by distinct mechanisms in sorghum and maize.
PMID- 26419899
TI - Silver-catalyzed regioselective [3+2] cycloaddition of arene-diazonium salts with
2,2,2-trifluorodiazoethane (CF3CHN2): a facile access to 2-aryl-5
trifluoromethyltetrazoles.
AB - A silver-catalyzed regioselective [3+2] cycloaddition reaction of arenediazonium
salts with 2,2,2-trifluorodiazoethane (CF3CHN2) is reported. Under mild
conditions, a series of 2-aryl substituted 5-trifluoromethyltetrazoles were
obtained in moderate to excellent yields with wide functional group
compatibility. Furthermore, this cycloaddition reaction could also be performed
in a one-pot diazotization/cycloaddition sequence from commercially available
aniline derivatives.
PMID- 26419900
TI - Long-lasting analgesic effect of transcranial direct current stimulation in
treatment of chronic endometriosis pain.
AB - Approximately 10-20% of women of reproductive age suffer from endometriosis, with
70-90% of these women reporting chronic pain symptoms that persist during their
menstrual cycle. We are presenting a case in which a novel form of noninvasive
brain stimulation called transcranial direct current stimulation was used as an
intervention in a 32-year-old woman with persistent, chronic pain symptoms caused
by endometriosis for 20 years. Ten daily, 20-min sessions of 2-mA anodal
transcranial direct current stimulation were applied over the left primary motor
cortex. Acutely, visual analog scale pain symptoms were reduced by 60%. There
were also significant decreases in modules of the Endometriosis Health Profile.
At the 4-month follow-up, the patient still expressed an overall decrease in pain
symptoms of 30%.
PMID- 26419901
TI - Suppressing cAMP response element-binding protein transcription shortens the
duration of status epilepticus and decreases the number of spontaneous seizures
in the pilocarpine model of epilepsy.
AB - OBJECTIVE: Current epilepsy therapies directed at altering the function of
neurotransmitter receptors or ion channels, or release of synaptic vesicles fail
to prevent seizures in approximately 30% of patients. A better understanding of
the molecular mechanism underlying epilepsy is needed to provide new therapeutic
targets. The activity of cyclic AMP (cAMP) response element-binding protein
(CREB), a major transcription factor promoting CRE-mediated transcription,
increases following a prolonged seizure called status epilepticus. It is also
increased in the seizure focus of patients with medically intractable focal
epilepsy. Herein we explored the effect of acute suppression of CREB activity on
status epilepticus and spontaneous seizures in a chronic epilepsy model. METHODS:
Pilocarpine chemoconvulsant was used to induce status epilepticus. To suppress
CREB activity, a transgenic mouse line expressing an inducible dominant negative
mutant of CREB (CREB(IR) ) with a serine to alanine 133 substitution was used.
Status epilepticus and spontaneous seizures of transgenic and wild-type mice were
analyzed using video-electroencephalography (EEG) to assess the effect of CREB
suppression on seizures. RESULTS: Our findings indicate that activation of
CREB(IR) shortens the duration of status epilepticus. The frequency of
spontaneous seizures decreased in mice with chronic epilepsy during CREB(IR)
induction; however, the duration of the spontaneous seizures was unchanged. Of
interest, we found significantly reduced levels of phospho-CREB Ser133 upon
activation of CREB(IR) , supporting prior work suggesting that binding to the CRE
site is important for CREB phosphorylation. SIGNIFICANCE: Our results suggest
that CRE transcription supports seizure activity both during status epilepticus
and in spontaneous seizures. Thus, blocking of CRE transcription is a novel
target for the treatment of epilepsy.
PMID- 26419902
TI - Expression of serine proteinase P186 of Arthrobotrys oligospora and analysis of
its nematode-degrading activity.
AB - The nematode-trapping fungi possess a unique capability of predating and invading
nematodes. As a representative nematode-trapping fungus, Arthrobotrys oligospora
has been widely used to study the interactions between nematode-trapping fungi
and their hosts. Serine proteinase is one of the important virulence factors
during process of invasion of the nematode-trapping fungi into nematodes. In this
study, using reverse transcription polymerase chain reaction, we amplified the
gene sequence of serine proteinase 186 from A. oligospora, cloned it into pPIC9K
vector and expressed it in the yeast Pichia pastoris. The expressed recombinant
serine proteinase186 (reP186) was purified via Ni-affinity chromatography. The in
vitro nematode-degrading activity of reP186 was analyzed. Sodium dodecyl sulfate
polyacrylamide gel electrophoresis and Western blot analysis revealed that reP186
with molecular weight of 33 kDa was successfully obtained. ReP186 was capable of
degrading a series of protein substrates including casein, gelatin, bovine serum
albumin, denatured collagen and nematode cortical layer. The reP186 exhibited the
maximal activity at pH 8.0 and 55 degrees C and was highly sensitive to the
inhibitor, phenylmethanesulfonylfluoride. Treatment of Caenorhabditis elegans and
Haemonchus contortus with reP186 for 12, 24 and 36 h, respectively, resulted in
62, 88 and 100 % of killing rates for C. elegans, and 52, 65 and 84 % of killing
rates for H. contortus, respectively, indicating a relatively strong nematode
degrading bioactivity of reP186.
PMID- 26419904
TI - Commentary on Kim Miller.
PMID- 26419903
TI - Rosiglitazone use and associated adverse event rates in Canada: an updated
analysis.
AB - BACKGROUND: We previously reported on the change in the use of rosiglitazone
containing products (RCP) and adverse event reporting rates in Canadian patients
between 2004 and 2010. The present study extends this analysis to include the
January 2011 to December 2012 time period. METHODS: RCP utilization rates were
obtained from IMS Health Brogan's longitudinal de-identified patient database,
LRx. GlaxoSmithKline's global adverse events database was used to extract adverse
events (AE), serious adverse events (SAE), and cardiac adverse events (CAE)
reported in Canadian patients receiving RCP from April 2004 to December 2012. The
patient utilization information from the LRx database was used to estimate rates
per 100,000 patients. RESULTS: An estimated 182,841 patients were dispensed RCP
prescriptions between April 2004 and December 2012. The total number of patients
using RCP decreased by 85% from 2011 to 2012. From its peak use in 2007, the
number of patients filling a prescription decreased 97%. A total of 1069 AEs were
reported during the study period, of which 32 AE's were reported from Jan 2011 to
Dec 2012. The average monthly reporting rates of AE's, SAE's and CAE's over 2011
2012 were 10.8/100,000 patients, 9.1/100,000 patients and 5.0/100,000 patients,
respectively. CONCLUSIONS: The utilization of RCP in Canada has significantly
declined. The significance of the adverse event rate information presented is
uncertain and must be evaluated within the context of the well known factors that
can influence AE reporting rates, as well as limitations to the methods used to
estimate these reporting rates.
PMID- 26419905
TI - Recruiting community health centers into pragmatic research: Findings from STOP
CRC.
AB - BACKGROUND: Challenges of recruiting participants into pragmatic trials,
particularly at the level of the health system, remain largely unexplored. As
part of Strategies and Opportunities to STOP Colon Cancer in Priority Populations
(STOP CRC), we recruited eight separate community health centers (consisting of
26 individual safety net clinics) into a large comparative effectiveness
pragmatic study to evaluate methods of raising the rates of colorectal cancer
screening. METHODS: In partnership with STOP CRC's advisory board, we defined
criteria to identify eligible health centers and applied these criteria to a list
of health centers in Washington, Oregon, and California affiliated with Oregon
Community Health Information Network, a 16-state practice-based research network
of federally sponsored health centers. Project staff contacted centers that met
eligibility criteria and arranged in-person meetings of key study investigators
with health center leadership teams. We used the Consolidated Framework for
Implementation Research to thematically analyze the content of discussions during
these meetings to identify major facilitators of and barriers to health center
participation. RESULTS: From an initial list of 41 health centers, 11 met the
initial inclusion criteria. Of these, leaders at three centers declined and at
eight centers (26 clinic sites) agreed to participate (73%). Participating and
nonparticipating health centers were similar with respect to clinic size, percent
Hispanic patients, and percent uninsured patients. Participating health centers
had higher proportions of Medicaid patients and higher baseline colorectal cancer
screening rates. Common facilitators of participation were perception by center
leadership that the project was an opportunity to increase colorectal cancer
screening rates and to use electronic health record tools for population
management. Barriers to participation were concerns of center leaders about
ability to provide fecal testing to and assure follow-up of uninsured patients,
limited clinic capacity to prepare mailings required by the study protocol,
discomfort with randomization, and concerns about delaying program implementation
at some clinics due to the research requirements. CONCLUSION: Our findings
address an important research gap and may inform future efforts to recruit
community health centers into pragmatic research.
PMID- 26419906
TI - Pigments influence the tolerance of Pseudomonas aeruginosa PAO1 to
photodynamically induced oxidative stress.
AB - Pseudomonas aeruginosa is an opportunistic pathogen known to be resistant to
different classes of antibiotics and disinfectants. P. aeruginosa also displays a
certain degree of tolerance to photodynamic therapy (PDT), an alternative
antimicrobial approach exploiting a photo-oxidative stress induced by exogenous
photosensitizers and visible light. To evaluate whether P. aeruginosa pigments
can contribute to its relative tolerance to PDT, we analysed the response to this
treatment of isogenic transposon mutants of P. aeruginosa PAO1 with altered
pigmentation. In general, in the presence of pigments a higher tolerance to PDT
induced photo-oxidative stress was observed. Hyperproduction of pyomelanin makes
the cells much more tolerant to stress caused by either radicals or singlet
oxygen generated by different photosensitizers upon photoactivation. Phenazines,
pyocyanin and phenazine-1-carboxylic acid, produced in different amounts
depending on the cultural conditions, are able to counteract both types of PDT
elicited reactive oxygen species. Hyperproduction of pyoverdine, caused by a
mutation in a quorum-sensing gene, rendered P. aeruginosa more tolerant to a
photosensitizer that generates mainly singlet oxygen, although in this case the
observed tolerance to photo-oxidative stress cannot be exclusively attributed to
the presence of the pigment.
PMID- 26419907
TI - Versatile and Amplified Biosensing through Enzymatic Cascade Reaction by Coupling
Alkaline Phosphatase in Situ Generation of Photoresponsive Nanozyme.
AB - The alkaline phosphatase (ALP) biocatalysis followed by the in situ enzymatic
generation of a visible light responsive nanozyme is coupled to elucidate a novel
amplification strategy by enzymatic cascade reaction for versatile biosensing.
The enzymatic hydrolysis of o-phosphonoxyphenol (OPP) to catechol (CA) by ALP is
allowed to coordinate on the surface of TiO2 nanoparticles (NPs) due to the
specificity and high affinity of enediol ligands to Ti(IV). Upon the stimuli by
CA generated from ALP, the inert TiO2 NPs is activated, which demonstrates highly
efficient oxidase mimicking activity for catalyzing the oxidation of the typical
substrate of 3,3',5,5'-tetramethylbenzidine (TMB) under visible light (lambda >=
400 nm) irradiation utilizing dissolved oxygen as an electron acceptor. On the
basis of the cascade reaction of ALP and the nanozyme of CA coordinated TiO2
(TiO2-CA) NPs, we design exquisitely colorimetric biosensors for probing ALP
activity and its inhibitor of 2, 4-dichlorophenoxyacetic acid (2,4-DA).
Quantitative probing of ALP activity in a wide linear range from 0.01 to 150 U/L
with the detection limit of 0.002 U/L is realized, which endows the methodology
with sufficiently high sensitivity for potentially practical applications in real
samples of human serum (ALP level of 40-190 U/L for adults). In addition, a novel
immunoassay protocol by taking mouse IgG as an example is validated using the
ALP/nanozyme cascade amplification reaction as the signal transducer. A low
detection limit of 2.0 pg/mL is attained for mouse IgG, which is 4500-fold lower
than that of the standard enzyme-linked immuno-sorbent assay (ELISA) kit.
Although only mouse IgG is used as a proof-of-concept in our experiment, we
believe that this approach is generalizable to be readily extended to other ELISA
systems. This methodology opens a new horizon for amplified and versatile
biosensing including probing ALP activity and following ALP-based ELISA
immunoassays.
PMID- 26419909
TI - Efficacy of Low-Density Lipoprotein Apheresis in Salvaging Critical Limb Ischemia
Induced by Acute Thrombotic Occlusion on Peripheral Artery Disease.
PMID- 26419908
TI - Clinical presentation and outcome by age categories in acute heart failure:
results from an international observational cohort.
AB - AIMS: To assess, according to age groups, patients' characteristics according to
region of origin, the chronic therapeutic management, prognostic utility of
clinical variables, and natriuretic peptides. METHODS AND RESULTS: The GREAT
registry consisted of patients identified as presenting with acute heart failure
at the emergency department. Four groups of patients were defined according to
age: the young patient group (<65 years); 'middle-old' (65-74 years), 'old-old'
(75-84 years) and the 'oldest-old' (85-94 years). Follow-up at 1 year was
performed via personal contact or national data registries at 1 year. Dataset
consisted of 14 758 patients aged up to 95 years, with the 'oldest-old' group
being more prevalent in North America and Western Europe. The 30-day mortality
rate were, respectively, 8.1%, 8.9%, 10.3%, and 16.3% among the four age groups
and 1-year mortality rates were, respectively, 3.1%, 17.1%, 24.7%, and 39.9%.
Chronic heart failure treatment was less frequently administered with age
(percentage of the 'fully treated' group was 14% in the 'young' compared with 2%
in the 'oldest-old' patient group). Reduced left ventricular ejection fraction
was present in 70%, 62.3%, 52.5%, and 46.8% among the four age groups,
respectively. The prognostic utility of most variables for short- and long-term
outcome was attenuated with age, with the exception of natriuretic peptides.
CONCLUSION: This study found a large heterogeneity in age among geographic
regions and that the eldest are less likely to be treated in accordance with
recommendations of current heart failure guidelines. Natriuretic peptide
concentrations retained prognostic value in patients across age strata.
PMID- 26419910
TI - Towards universal health coverage for reproductive health services in Ethiopia:
two policy recommendations.
AB - Reproductive health services are crucial for maternal and child health, but
universal health coverage is still not within reach in most societies. Ethiopia's
goal of universal health coverage promises access to all necessary services for
everyone while providing protection against financial risk. When moving towards
universal health coverage, health plans and policies require contextualized
knowledge about baseline indicators and their distributions. To understand more
about the factors that explain coverage, we study the relationship between
socioeconomic and geographic factors and the use of reproductive health services
in Ethiopia, and further explore inequalities in reproductive health coverage.
Based on these findings, we discuss the normative implications of these findings
for health policy. Using population-level data from the Ethiopian Demographic and
Health Survey (2011) in a multivariate logistic model, we find that family
planning and use of antenatal care are associated with higher wealth, higher
education and being employed. Skilled attendance at birth is associated with
higher wealth, higher education, and urban location. There is large variation
between Addis Ababa (the capital) and other administrative regions. Concentration
indices show substantial inequalities in the use of reproductive health services.
Decomposition of the concentration indices indicates that difference in wealth is
the most important explanatory factor for inequality in reproductive health
coverage, but other factors, such as urban setting and previous health care use,
are also associated with inequalities. When aiming for universal health coverage,
this study shows that different socioeconomic factors as well as health-sector
factors should be addressed. Our study re-confirms the importance of a broader
approach to reproductive health, and in particular the importance of inequality
in wealth and geography. Poor, non-educated, non-employed women in rural areas
are multidimensionally worse off. The needs of these women should be addressed
through elimination of out-of-pocket costs and revision of the formula for
resource allocation between regions as Ethiopia moves towards universal health
coverage.
PMID- 26419911
TI - Is immune system-related hypertension associated with ovarian hormone deficiency?
AB - NEW FINDINGS: What is the topic of this review? This review summarizes recent
data on the role of ovarian hormones and sex in inflammation-related
hypertension. What advances does it highlight? The adaptive immune system has
recently been implicated in the development of hypertension in males but not in
females. The role of the immune system in the development of hypertension in
women and its relationship to ovarian hormone production are highlighted. The
immune system is known to contribute to the development of high blood pressure in
males. However, the role of the immune system in the development of high blood
pressure in females and the role of ovarian hormones has only recently begun to
be studied. In animal studies, both the sex of the host and the T cell are
critical biological determinants of susceptibility and resistance to hypertension
induced by angiotensin II. In women, natural menopause is known to result in
significant changes in the expression of genes regulating the immune system.
Likewise, in animal models, ovariectomy results in hypertension and an
upregulation in T-cell tumour necrosis factor-alpha-related genes. Oestrogen
replacement results in decreases in inflammatory genes in the brain regions
involved in blood pressure regulation. Together, these studies suggest that the
response of the adaptive immune system to ovarian hormone deficiency is a
significant contributor to hypertension in women.
PMID- 26419912
TI - An analysis of child protection 'standard operating procedures for research' in
higher education institutions in the United Kingdom.
AB - BACKGROUND: Interest in children's agency within the research process has led to
a renewed consideration of the relationships between researchers and children.
Child protection concerns are sometimes not recognised by researchers, and
sometimes ignored. Yet much research on children's lives, especially in health,
has the potential to uncover child abuse. University research guidance should be
in place to safeguard both researchers and the populations under scrutiny. The
aim of this study was to examine university guidance on protecting children in
research contexts. METHODS: Child protection Standard Operating Procedures (SOPs)
were requested from institutions with Research Assessment Exercise (2008)
profiles in the top two quartiles according to published league tables.
Procedures were included if they applied across the institution and if they were
more extensive than stating the university's general application of the UK
Disclosure and Barring Service process. A typology for scoring the SOPs was
designed for this study based on the authors' previous work. The typology and the
raw data scoring were reviewed independently by each of the team members and
collectively agreed. The raw scores were charted and analysed using descriptive
statistics. RESULTS: SOPs for research conduct amongst vulnerable groups were
sought from 83 institutions. Forty HEIs provided policies which met the inclusion
criteria. The majority did not mention children, young people or vulnerable
adults as a whole, although children in nurseries and young people in
universities were addressed. Only three institutions scored over 50 out of a
possible 100. The mean score was 17.4. More than half the HEIs made no reference
to vetting/barring schemes in research, only eight universities set out a
training programme on child protection. Research was often not mentioned in the
SOPs and only six mention children in research, with only two fully recognising
the extent of child protection in research. DISCUSSION: There is potential for
researchers to recognise and respond to maltreatment of children who participate
in research. However, the majority of HEIs do not have an overt culture of
safeguarding. There is confusion over what are the roles and responsibilities of
HEIs in relation to research that involves children. CONCLUSIONS: The policies
that are meant to support and guide research practice, so that children are
protected, are in the most part non-existent or poorly developed.
PMID- 26419913
TI - Stem cell treatment for acute myocardial infarction.
AB - BACKGROUND: Cell transplantation offers a potential therapeutic approach to the
repair and regeneration of damaged vascular and cardiac tissue after acute
myocardial infarction (AMI). This has resulted in multiple randomised controlled
trials (RCTs) across the world. OBJECTIVES: To determine the safety and efficacy
of autologous adult bone marrow stem cells as a treatment for acute myocardial
infarction (AMI), focusing on clinical outcomes. SEARCH METHODS: This Cochrane
review is an update of a previous version (published in 2012). We searched the
Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 2), MEDLINE
(1950 to March 2015), EMBASE (1974 to March 2015), CINAHL (1982 to March 2015)
and the Transfusion Evidence Library (1980 to March 2015). In addition, we
searched several international and ongoing trial databases in March 2015 and
handsearched relevant conference proceedings to January 2011. SELECTION CRITERIA:
RCTs comparing autologous bone marrow-derived cells with no cells in patients
diagnosed with AMI were eligible. DATA COLLECTION AND ANALYSIS: Two review
authors independently screened all references, assessed the risk of bias of the
included trials and extracted data. We conducted meta-analyses using random
effects models throughout. We analysed outcomes at short-term (less than 12
months) and long-term (12 months or more) follow-up. Dichotomous outcomes are
reported as risk ratio (RR) and continuous outcomes are reported as mean
difference (MD) or standardised MD (SMD). We performed sensitivity analyses to
evaluate the results in the context of the risk of selection, performance and
attrition bias. Exploratory subgroup analysis investigated the effects of
baseline cardiac function (left ventricular ejection fraction, LVEF) and cell
dose, type and timing of administration, as well as the use of heparin in the
final cell solution. MAIN RESULTS: Forty-one RCTs with a total of 2732
participants (1564 cell therapy, 1168 controls) were eligible for inclusion. Cell
treatment was not associated with any changes in the risk of all-cause mortality
(34/538 versus 32/458; RR 0.93, 95% CI 0.58 to 1.50; 996 participants; 14
studies; moderate quality evidence), cardiovascular mortality (23/277 versus
18/250; RR 1.04, 95% CI 0.54 to 1.99; 527 participants; nine studies; moderate
quality evidence) or a composite measure of mortality, reinfarction and re
hospitalisation for heart failure (24/262 versus 33/235; RR 0.63, 95% CI 0.36 to
1.10; 497 participants; six studies; moderate quality evidence) at long-term
follow-up. Statistical heterogeneity was low (I(2) = 0% to 12%). Serious
periprocedural adverse events were rare and were generally unlikely to be related
to cell therapy. Additionally, cell therapy had no effect on morbidity, quality
of life/performance or LVEF measured by magnetic resonance imaging. Meta-analyses
of LVEF measured by echocardiography, single photon emission computed tomography
and left ventricular angiography showed evidence of differences in mean LVEF
between treatment groups although the mean differences ranged between 2% and 5%,
which are accepted not to be clinically relevant. Results were robust to the risk
of selection, performance and attrition bias from individual studies. AUTHORS'
CONCLUSIONS: The results of this review suggest that there is insufficient
evidence for a beneficial effect of cell therapy for AMI patients. However, most
of the evidence comes from small trials that showed no difference in clinically
relevant outcomes. Further adequately powered trials are needed and until then
the efficacy of this intervention remains unproven.
PMID- 26419916
TI - Foreword.
PMID- 26419914
TI - Approximation of head and neck cancer volumes in contrast enhanced CT.
AB - BACKGROUND: Tumor volume may serve as a predictor of response to
radiochemotherapy (RCT) in head and neck squamous cell carcinoma (HNSCC).
Computer assisted tumor volumetry requires time-consuming slice-by-slice manual
or semi-automated segmentation. We questioned how accurately primary tumor and
suspect cervical lymph node (LN) volumes can be approximated by the maximum tumor
diameters in three dimensions. METHODS: In contrast-enhanced diagnostic CT scans
of 74 patients with incident advanced HNSCC, manual slice-by-slice segmentation
volumetry of primary tumor, total- and largest suspect cervical LN served as the
reference method. In the same scans, maximum orthogonal diameters were measured
using the distance measurement tool in standard visualization software in axial
and coronal sections. From these diameters, approximate volumes were calculated
using the cubic and ellipsoid formula. A second segmentation volumetry was
performed in contrast enhanced radiotherapy-planning CT scans obtained prior to
primary concurrent RCT 24 days (+/- 13 days) following the initial diagnostic CT
scans. Intraclass correlation coefficients and Bland-Altman analyses were used to
compare results. RESULTS: Slice-by-slice manual segmentation volumetry of primary
and LN volumes revealed a lognormal distribution and ranged from 0 to 86 ml and 0
to 129 ml, respectively. Volume approximations in diagnostic CT scans with the
ellipsoid formula resulted in an -8 % underestimation of tumor volumes (95 % CI
14 % to -1 %; p = 0.022) and an -18 % underestimation of suspect cervical LN
volumes (95 % CI -25 % to -12 %; p = 0.001). Inter rater intraclass correlation
for primaries was 0.95 (95 % CI +0.92 to +0.97; p = 0.001), and intra rater
intraclass correlation was 0.99 (95 % CI +0.98 to +0.99; p = 0.001). The cubic
formula resulted in pronounced overestimation of primary and LN volumes. Primary
tumor volumes obtained by the second segmentation volumetry in radiotherapy
planning CT scans obtained on average 24 days following the initial volumetry
resulted in larger primary tumor volumes (mean bias +28 %, 95 % CI +14 % to +41
%; p = 0.001). Tumor volume increase correlated with time between the diagnostic
and planning CTs (r = 0.24, p = 0.05) and was approximately 1 % per day.
DISCUSSION: Ellipsoid approximations of tumor and lymph node volumes in HNSCC
using maximum orthogonal diameters underestimates volumes based on segmentation
in multiple slices. Due to time difference and safety margins, segmented volumes
in radiotherapy-planning CT scans tend to be larger than in diagnostic CT scans.
CONCLUSION: Ellipsoid approximations of tumor and lymph node volumes in HNSCC are
easily available from diagnostic CT scans. Volume estimates are applicable over a
wide range of tumor and LN sizes and may be useful in clinical decision-making
and oncologic research.
PMID- 26419915
TI - Diverse regulatory factors associate with flowering time and yield responses in
winter-type Brassica napus.
AB - BACKGROUND: Flowering time, plant height and seed yield are strongly influenced
by climatic and day-length adaptation in crop plants. To investigate these traits
under highly diverse field conditions in the important oilseed crop Brassica
napus, we performed a genome-wide association study using data from diverse
agroecological environments spanning three continents. METHODS: A total of 158
European winter-type B.napus inbred lines were genotyped with 21,623 unique,
single-locus single-nucleotide polymorphism (SNP) markers using the Brassica 60 K
SNP Illumina(r) Infinium consortium array. Phenotypic associations were
calculated in the panel over the years 2010-2012 for flowering time, plant height
and seed yield in 5 highly diverse locations in Germany, China and Chile, adding
up to 11 diverse environments in total. RESULTS: We identified 101 genome regions
associating with the onset of flowering, 69 with plant height, 36 with seed yield
and 68 cross-trait regions with potential adaptive value. Within these regions,
B.napus orthologs for a number of candidate adaptation genes were detected,
including central circadian clock components like CIRCADIAN CLOCK- ASSOCIATED 1
(Bna.CCA1) and the important flowering-time regulators FLOWERING LOCUS T (Bna.FT)
and FRUITFUL (Bna.FUL). DISCUSSION: Gene ontology (GO) enrichment analysis of
candidate regions suggested that selection of genes involved in post
transcriptional and epigenetic regulation of flowering time may play a potential
role in adaptation of B. napus to highly divergent environments. The classical
flowering time regulators Bna.FLC and Bna.CO were not found among the candidate
regions, although both show functional variation. Allelic effects were additive
for plant height and yield, but not for flowering time. The scarcity of positive
minor alleles for yield in this breeding pool points to a lack of diversity for
adaptation that could restrict yield gain in the face of environmental change.
CONCLUSIONS: Our study provides a valuable framework to further improve the
adaptability and yield stability of this recent allopolyploid crop under changing
environments. The results suggest that flowering time regulation within an
adapted B. napus breeding pool is driven by a high number of small modulating
processes rather than major transcription factors like Bna.CO. In contrast, yield
regulation appears highly parallel, therefore yield could be increased by
pyramiding positively associated haplotypes.
PMID- 26419917
TI - What potential is there for liposomal-based nanotherapy for the treatment of Type
1 diabetes?
PMID- 26419918
TI - Early communication deficits in the Shank1 knockout mouse model for autism
spectrum disorder: Developmental aspects and effects of social context.
AB - Alterations in SHANK genes were repeatedly reported in autism spectrum disorder
(ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent
deficits in social communication/interaction across multiple contexts, with
restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD
are purely behaviorally defined and reliable biomarkers have still not been
identified. The validity of mouse models for ASD therefore strongly relies on
their behavioral phenotype. Here, we studied communication by means of isolation
induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by
comparing Shank1(-/-) null mutant, Shank1(+/-) heterozygous, and Shank1(+/+)
wildtype littermate controls. The first aim of the present study was to evaluate
the effects of Shank1 deletions on developmental aspects of communication in
order to see whether ASD-related communication deficits are due to general
impairment or delay in development. Second, we focused on social context effects
on USV production. We show that Shank1(-/-) pups vocalized less and displayed a
delay in the typical inverted U-shaped developmental USV emission pattern with
USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype
difference on PND6. Moreover, testing under social conditions revealed even more
prominently genotype-dependent deficits regardless of the familiarity of the
social context. As communication by definition serves a social function,
introducing a social component to the typically nonsocial test environment could
therefore help to reveal communication deficits in mouse models for ASD.
Together, these results indicate that SHANK1 is involved in acoustic
communication across species, with genetic alterations in SHANK1 resulting in
social communication/interaction deficits. Autism Res 2016, 9: 696-709. (c) 2015
International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 26419919
TI - The Predictive Power of the Annellation Theory: The Case of the C26H16 Cata
Condensed Benzenoid Polycyclic Aromatic Hydrocarbons.
AB - The Annellation Theory was applied to establish the locations of maximum
absorbance for the p and beta bands in the UV-vis spectra of eight benzenoid cata
condensed polycyclic aromatic hydrocarbons (PAHs) with molecular formula C26H16
and no available syntheses procedures. In this group of eight isomers, there are
seven compounds with potential carcinogenic properties due to geometrical
constraints. In addition, crude oil and asphaltene absorption spectra exhibit
similar properties, and the PAHs in heavier crude oils and asphaltenes are known
to be the source of the color of heavy oils. Therefore, understanding the
electronic bands of PAHs is becoming increasingly important. The methodology was
validated using information for the remaining 29 isomers with available UV-vis
spectra. The results satisfactorily agree with the results from semiempirical
calculations made using the ZINDO/S approach. The locations of maximum absorbance
for the p and beta bands in the UV-vis spectra of the eight C26H16 cata-condensed
isomers dibenzo[c,m]tetraphene, naphtho[1,2-c]chrysene, dibenzo[c,f]tetraphene,
benzo[f]picene, naphtho[2,1-a]tetraphene, naphtho[2,1-c]tetraphene,
dibenzo[c,l]chrysene, and naphtho[1,2-a]tetraphene were established for the first
time.
PMID- 26419920
TI - Developing Research Knowledge and Competence in Master's Students:
Individualizing Group Research Projects.
PMID- 26419921
TI - Lewis acid-promoted [2 + 2] cycloadditions of alkenes with aryl ketenes.
AB - A method for the [2 + 2] cycloaddition of aryl ketenes and alkenes is presented.
The process involves the in situ generation of a ketene in the presence of a
Lewis acid. The utility of products is demonstrated towards the synthesis of a
common scaffold found in several natural product families.
PMID- 26419922
TI - Pharmacokinetic considerations in the treatment of multiple sclerosis with
interferon-beta.
AB - INTRODUCTION: Interferon-beta (IFNbeta) is well established as a disease
modifying treatment for patients with multiple sclerosis. Several preparations of
the biopharmaceutical are available differing in protein structure, formulation,
dose as well as frequency and route of administration. Recently, a pegylated form
of IFNbeta has been marketed. AREAS COVERED: Following a PubMed database search,
we provide an overview of what is presently known about the pharmacokinetics (PK)
of IFNbeta including its absorption, distribution, metabolism and elimination.
Also, we discuss the association with clinically relevant issues such as
treatment efficacy, adverse events and anti-drug antibodies. EXPERT OPINION:
IFNbeta has a bioavailability of ~ 30% after subcutaneous or intramuscular
administration, shows peak serum concentrations within several hours, has a half
life of < 1 day and is eliminated by a renal and hepatic pathway. PK parameters
do not substantially differ between the types of IFNbeta and routes of
administration; only pegylation of IFNbeta results in substantially increased and
prolonged PK. Although no clinical dose-effect relationship could be established,
there is an association of IFNbeta dose with magnetic resonance imaging outcome
parameters. Furthermore, there is an association of IFNbeta serum levels with the
occurrence of adverse events and anti-drug antibodies.
PMID- 26419923
TI - Trends in Authorship Patterns in High-Impact Radiology Publications, 1980-2013.
AB - RATIONALE AND OBJECTIVES: Concerns have been raised about authorship inflation in
medical literature. The purpose of this study was to determine how the number of
authors per radiology article has changed over time with regard to study type and
geographic factors. MATERIALS AND METHODS: We collected data on study type,
authorship count, and the country of the corresponding author for a sample of
articles published in Radiology, American Journal of Roentgenology, and European
Radiology in 1980, 1990, 2000, and 2013. Only original research and review
articles were considered. We computed trends in the mean number of authors per
article for each journal and compared authorship trends between study types and
geographic region. The study did not involve human subjects and was therefore
exempt from institutional board review at our institution. RESULTS: A total of
682 articles were reviewed, of which 572 were original research articles (83.9%)
and 110 review articles (16.1%). The overall number of authors per article
doubled from 3.6 in 1980 to 7.3 in 2013 (P < .001). From 1990 to 2013, the
largest absolute increase in authorship count was in Radiology (4.4-8.1, 84.1%, P
< .001). The largest increase in authorship occurred in original research
articles (3.7-7.8, 111%, P < .001). Although authorship counts were greatest in
Asia over most study period, growth in authorship count was highest in Europe.
CONCLUSIONS: Authorship count has dramatically increased in radiology journals in
the last 3 decades, particularly in original research articles and in Europe.
PMID- 26419924
TI - Selective and sensitive determination of protoberberines by capillary
electrophoresis coupled with molecularly imprinted microextraction.
AB - In this work, we developed a novel molecularly imprinted solid-phase
microextraction with capillary electrophoresis method for the selective
extraction and determination of protoberberines in complicated samples. The
imprinted monolith was prepared in a micropipette tip-based device by using
acrylamide as the functional monomer, ethyleneglyoldimethacrylate as the cross
linker and dimethylsulfoxide as the porogen, and exhibited an imprinting factor
of 2.41 to berberine, 2.36 to palmatine and 2.38 to jatrorrhizine. Good capillary
electrophoresis separation was achieved by using 20 mM phosphate buffer at pH 7
as running buffer with the addition of organic modifier of 10% methanol.
Parameters such as sample pH value, sample flow rate and sample volume were
investigated for imprinted monolith-based solid-phase microextraction. An
imprinted solid-phase microextraction with capillary electrophoresis method was
developed, the method showed a wide linear range (0.3-50 MUg/mL), good linearity
(R2 >= 0.9947) and good reproducibility (relative standard deviations <= 0.73%),
the limit of detection was as low as 0.1 MUg/mL, which was lower than some
reported methods based on capillary electrophoresis for protoberberines. The
method has been applied for determination of three common protoberberines in
Cortex Phellodendri Chinensis, by using a molecularly imprinted monolith as the
selective sorbent, most of the matrices in the Cortex Phellodendri Chinensis
sample were removed and three protoberberines were selectively enriched and well
determined.
PMID- 26419925
TI - Risk of Intestinal Malignancy in Patients With Short Bowel Syndrome.
AB - BACKGROUND: Postresection intestinal adaptation is an augmented self-renewal
process that might increase the risk of malignant transformation in the
intestine. Furthermore, patients with short bowel syndrome (SBS) have other
characteristics that might increase this risk. Our aim was to determine the
incidence of new intestinal malignancy in SBS patients. METHODS: We reviewed the
records of 500 adult SBS patients identified from 1982-2013. There were 199 men
and 301 women ranging in age from 19-91 years. Follow-up from the time of
diagnosis of SBS ranged from 12-484 months. A total of 186 (37%) patients were
followed >5 years. RESULTS: The cause of SBS was postoperative in 35% of
patients, malignancy/radiation in 19%, mesenteric vascular disease in 17%,
Crohn's disease in 16%, and other in 13%. Twenty-eight (6%) patients received
growth stimulatory medications. Fifteen percent of patients had a prior total
colectomy. Twenty-eight (6%) patients underwent intestinal transplantation, and
115 (23%) patients had a previous abdominal malignancy, including colorectal
cancer in 43 patients. Thirty-six (7%) received radiation therapy. Recurrent
colon cancer was found in 2 patients, one at a stoma and the other with lung
metastases. New colon cancer was found in 1 patient (0.2%), a 62-year-old woman
with long-standing Crohn's disease. CONCLUSION: The incidence of colon cancer in
this heterogenous group of patients with SBS was similar to that of the normal
population. This suggests that the risk of developing a new colon cancer in
patients with SBS is not increased.
PMID- 26419926
TI - Review of a two-year methicillin-resistant Staphylococcus aureus screening
program and cost-effectiveness analysis in Singapore.
AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) poses an
increasingly large disease and economic burden worldwide. The effectiveness of
screening programs in the tropics is poorly understood. The aims of this study
are: (i) to analyze the factors affecting MRSA colonization at admission and
acquisition during hospitalization and (ii) to evaluate the cost-effectiveness of
a screening program which aims to control MRSA incidence during hospitalization.
METHODS: We conducted a retrospective case-control study of patients admitted to
the Communicable Disease Centre (CDC) in Singapore between Jan 2009 and Dec 2010
when there was an ongoing selective screening and isolation program. Risk factors
contributing to MRSA colonization on admission and acquisition during hospital
stay were evaluated using a logistic regression model. In addition, a cost
effectiveness analysis was conducted to determine the cost per disability
adjusted life year (DALY) averted due to implementing the screening and isolation
program. RESULTS: The average prevalence rate of screened patients at admission
and the average acquisition rate at discharge during the study period were 12.1
and 4.8 % respectively. Logistic regression models showed that older age
(adjusted odds ratio (OR) 1.03, 95 % CI 1.02-1.04, p < 0.001) and dermatological
conditions (adjusted OR 1.49, 95 % CI 1.11-1.20, p = 0.008) were independently
associated with an increased risk of MRSA colonization at admission. Age
(adjusted OR 1.02, 95 % CI 1.01-1.03, p = 0.002) and length of stay in hospital
(adjusted OR 1.04, 95 % CI 1.03-1.06, p < 0.001) were independent factors
associated with MRSA acquisition during hospitalization. The screening and
isolation program reduced the acquisition rate by 1.6 % and was found to be cost
saving. For the whole study period, the program cost US$129,916, while it offset
hospitalization costs of US$103,869 and loss of productivity costs of US$50,453
with -400 $/DALY averted. DISCUSSION: This study is the first to our knowledge
that evaluates the cost-effectiveness of screening and isolation of MRSA patients
in a tropical country. Another unique feature of the analysis is the evaluation
of acquisition rates among specific types of patients (dermatological, HIV and
infectious disease patients)and the comparison of the cost-effectiveness of
screening and isolation between them. CONCLUSIONS: Overall our results indicate
high MRSA prevalence that can be cost effectively reduced by selective screening
and isolation programs in Singapore.
PMID- 26419928
TI - Promyelocytic leukemia zinc finger mediates glucocorticoid-induced cell cycle
arrest in the chondroprogenitor cell line ATDC5.
AB - Glucocorticoids (GCs) affect the proliferation of growth plate chondrocytes. In
this study, we investigated the role of the GC-inducible promyelocytic leukemia
zinc finger (PLZF) gene in chondrocyte differentiation by using the chondrogenic
cell line ATDC5. PLZF overexpression suppressed cell cycle progression (p < 0.01)
and promoted differentiation into hypertrophic chondrocytes by inducing mRNA
expression of alkaline phosphatase (p < 0.01), and the cyclin-dependent kinase
(CDK) inhibitor p21 (p < 0.01). In contrast, PLZF knockdown impaired
differentiation into hypertrophic chondrocytes and promoted cell cycle
progression (p < 0.01). Treatment with the GC analogue dexamethasone (10(-6) M)
suppressed cell cycle progression in ATDC5 cells. PLZF shRNA attenuated
dexamethasone-induced cell cycle arrest (p < 0.01) by downregulating the mRNA
expression of the CDK inhibitors p21 and p57 (p < 0.01). These results clearly
indicated that PLZF promoted differentiation into hypertrophic chondrocytes and
mediated dexamethasone-induced cell cycle arrest by regulating CDK inhibitors.
PMID- 26419927
TI - Fingolimod induces neuroprotective factors in human astrocytes.
AB - BACKGROUND: Fingolimod (FTY720) is the first sphingosine-1-phosphate (S1P)
receptor modulator approved for the treatment of multiple sclerosis. The
phosphorylated active metabolite FTY720-phosphate (FTY-P) interferes with
lymphocyte trafficking. In addition, it accumulates in the CNS and reduces brain
atrophy in multiple sclerosis (MS), and neuroprotective effects are hypothesized.
METHODS: Human primary astrocytes as well as human astrocytoma cells were
stimulated with FTY-P or S1P. We analyzed gene expression by a genome-wide
microarray and validated induced candidate genes by quantitative PCR (qPCR) and
ELISA. To identify the S1P-receptor subtypes involved, we applied a membrane
impermeable S1P analog (dihydro-S1P), receptor subtype specific agonists and
antagonists, as well as RNAi silencing. RESULTS: FTY-P induced leukemia
inhibitory factor (LIF), interleukin 11 (IL11), and heparin-binding EGF-like
growth factor (HBEGF) mRNA, as well as secretion of LIF and IL11 protein. In
order to mimic an inflammatory milieu as observed in active MS lesions, we
combined FTY-P application with tumor necrosis factor (TNF). In the presence of
this key inflammatory cytokine, FTY-P synergistically induced LIF, HBEGF, and
IL11 mRNA, as well as secretion of LIF and IL11 protein. TNF itself induced
inflammatory, B-cell promoting, and antiviral factors (CXCL10, BAFF, MX1, and
OAS2). Their induction was blocked by FTY-P. After continuous exposure of cells
to FTY-P or S1P for up to 7 days, the extent of induction of neurotrophic factors
and the suppression of TNF-induced inflammatory genes declined but was still
detectable. The induction of neurotrophic factors was mediated via surface S1P
receptors 1 (S1PR1) and 3 (S1PR3). CONCLUSIONS: We identified effects of FTY-P on
astrocytes, namely induction of neurotrophic mediators (LIF, HBEGF, and IL11) and
inhibition of TNF-induced inflammatory genes (CXCL10, BAFF, MX1, and OAS2). This
supports the view that a part of the effects of fingolimod may be mediated via
astrocytes.
PMID- 26419929
TI - C1q/TNF-Related Protein 9 (CTRP9) attenuates hepatic steatosis via the autophagy
mediated inhibition of endoplasmic reticulum stress.
AB - C1q/TNF-Related Protein (CTRP) 9, the closest paralog of adiponectin, has been
reported to protect against diet-induced obesity and non-alcoholic fatty liver
disease (NAFLD). However, the underlying mechanism has not been fully elucidated.
We explored the protective effect of CTRP9 against hepatic steatosis and
apoptosis, and identified the mechanisms through autophagy and endoplasmic
reticulum (ER) stress using in vitro and in vivo experiments. Treating HepG2
cells with human recombinant CTRP9 significantly ameliorated palmitate- or
tunicamycin-induced dysregulation of lipid metabolism, caspase 3 activity and
chromatin condensation, which lead to reduction of hepatic triglyceride (TG)
accumulation. CTRP9 treatment induced autophagy markers including LC3 conversion,
P62 degradation, Beclin1 and ATG7 through AMPK phosphorylation in human primary
hepatocytes. Furthermore, CTRP9 decreased palmitate- or tunicamycin-induced ER
stress markers, such as eIF2alpha, CHOP and IRE-1, in HepG2 cells. Compound C, an
AMPK inhibitor, and 3 methyladenine (3 MA), an autophagy inhibitor, canceled the
effects of CTRP9 on ER stress, apoptosis and hepatic steatosis. In the livers of
HFD-fed mice, adenovirus-mediated CTRP9 overexpression significantly induced AMPK
phosphorylation and autophagy, whereas suppressed ER stress markers. In addition,
both SREBP1-mediated lipogenic gene expression and apoptosis were significantly
attenuated, which result in improvement in hepatic steatosis by overexpression of
CTRP9. These results demonstrate that CTRP9 alleviates hepatic steatosis through
relief of ER stress via the AMPK-mediated induction of autophagy.
PMID- 26419930
TI - Positive skeletal effect of two ingredients of Psoralea corylifolia L. on
estrogen deficiency-induced osteoporosis and the possible mechanisms of action.
AB - Estrogen replacement therapy (ERT) is utilized as a major regime for treatment of
postmenopausal osteoporosis at present. However, long-term supplement of estrogen
may cause uterine hyperplasia and hypertension leading to a high risk of
endometrial cancer and breast cancer. Psoralea corylifolia L. has long been used
as tonic and food additives in many countries. Previous studies had found two
ingredients in P. corylifolia L.: bavachin and bakuchiol exhibited osteoblastic
activity. The present study was designed to investigate the protective effect of
bakuchiol and bavachin on ovariectomy-induced bone loss and explore the possible
mechanism. In vivo, bakuchiol and bavachin could prevented estrogen deficiency
induced bone loss in ovariectomized rats without uterotrophic activity. In vitro
studies suggested that bakuchiol and bavachin induced primary human osteoblast
differentiation by up-regulating the Wnt signalling pathway. This study suggests
that such a bone-protective role makes them a promising and safe estrogen
supplement for the ERT.
PMID- 26419931
TI - The function of miR-199a-5p/Klotho regulating TLR4/NF-kappaB p65/NGAL pathways in
rat mesangial cells cultured with high glucose and the mechanism.
AB - Anti-aging protein Klotho may confer a renal protective effect via attenuating
the nuclear factor-kappaB (NF-kappaB) p65 pathways activity. Besides, miR-199a-5p
can promote gastric cancer by inhibition of Klotho protein expression. But little
is known regarding to the role of miR-199a-5p/Klotho in regulating NF-kappaB p65
pathways in the pathogenesis of diabetic kidney disease (DKD). Thus, we explored
Klotho and miR-199a-5p in terms of Toll-like receptor-4 (TLR4)/NF-kappaB
p65/neutrophil gelatinase associated lipocalin (NGAL) signaling pathways in high
glucose cultured mesangial cells (MCs). We found that high glucose increased miR
199a-5p expression, accompanied by the significantly decreased Klotho expression
at both mRNA and protein. High glucose also activated TLR4/NF-kappaB p65/NGAL
signaling pathways and promoted the downstream fibrosis and inflammatory
reaction. Additionally, inhibition of miR-199a-5p or exogenous addition of Klotho
restrained the activity of TLR4/NF-kappaB p65/NGAL signaling pathways, which in
turn suppressed the inflammation and fibrosis in high glucose cultured MCs. This
study provides a new basis to elucidate the protection mechanism of anti-aging
protein Klotho in diabetic kidney. For the first time, our study prompts that miR
199a-5p can be used as a new therapeutic targets for DKD.
PMID- 26419932
TI - miR-96 suppresses renal cell carcinoma invasion via downregulation of Ezrin
expression.
AB - BACKGROUND: The present study examined the role of microRNA (miR)-96 in renal
cell carcinoma (RCC) invasion. METHODS: The expression of miR-96 was detected by
quantitative reverse transcription-polymerase chain reaction in human RCC cell
lines with high (Caki-1) and low (786-O) metastatic potential. Invasive ability
and Ezrin expression were assessed in Caki-1 and 786-O cells transfected with a
miR-96 mimic or inhibitor using wound healing assays, Transwell assays and
western blotting. Expression of miR-96 and Ezrin was also examined in primary RCC
samples from 17 patients with metastatic disease and 46 patients who maintained
remission during a follow-up period of 37 months. RESULTS: miR-96 expression was
significantly lower in Caki-1compared to786-O cells. The invasive ability of Caki
1 and 786-O cells increased following transfection of cells with miR-96
inhibitor, whereas it decreased following transfection with miR-96 mimic. Ezrin
levels were negatively correlated with miR-96 in RCC, and inhibition of Ezrin
expression suppressed the miR-96-induced change in invasive ability. The negative
correlation between miR-96 and metastasis/Ezrin expression was also observed in
human RCC specimens. CONCLUSIONS: These results suggest that miR-96 suppresses
RCC invasion by modulating Ezrin expression.
PMID- 26419933
TI - A brain mass in a patient with Behcet's disease: a case report.
AB - INTRODUCTION: This case report describes an uncommon presentation of Behcet's
disease which manifested as neuro-Behcet's disease. Although it is not the first
reported case in the medical literature, it is a possible differential in a
patient presenting with a brain tumor. Since the diagnosis of neuro-Behcet's
disease depends largely on the clinical picture and medical history, it should be
considered prior to opting for invasive diagnostic methods. CASE PRESENTATION:
Our patient is a 36-year-old white man from Kuwait. He presented with acute onset
of headache, vomiting, and right-sided weakness. Magnetic resonance imaging of
his brain showed a mass in the brain stem. He then revealed that he had a history
of recurrent painful oral and genital ulcers for the past 10 years, which
suggested a diagnosis of Behcet's disease. A brain biopsy was recommended by a
neurosurgeon at the time, but the patient refused the procedure. After initiating
steroid therapy, the mass began to regress and, eventually, was undetectable on
subsequent imaging of his brain. CONCLUSIONS: This case of neuro-Behcet's disease
reflects the need to consider this diagnosis in a patient of less than 40 years
of age presenting with a suspected brain tumor. This may delay the need for
invasive diagnostic methods, especially if such methods are not desired by the
patient. In the management of suspected neuro-Behcet's disease, initiating
steroid therapy and measuring the response is a reasonable option before seeking
a definitive diagnosis via brain biopsy. If the response to steroids is minimal
then a brain biopsy should be performed.
PMID- 26419935
TI - Combined use of anterolateral thigh flap and pharyngeal flap for reconstruction
of extensive soft-palate defects.
AB - BACKGROUND: Functional reconstruction of extensive soft-palate defects is
challenging for microsurgeons. The versatility of the combination of a free
anterolateral thigh flap and a superiorly based pharyngeal flap for oncologic
soft-palate reconstruction was investigated. METHODS: The combination of flaps
was used for immediate reconstruction after total or subtotal resection of the
soft palate in five consecutive patients from 2006 to 2011. RESULTS: All flaps
survived completely. Palatal fistula and miniplate infection each developed in
one patient but healed conservatively. Follow-up period ranged from 21 to 66
months. All patients tolerated a regular diet without significant aspiration or
nasal regurgitation. Speech intelligibility was excellent in all patients, and
none required a palatal prosthesis. CONCLUSIONS: The combination of an
anterolateral thigh flap and a superiorly based pharyngeal flap is a versatile
option for reconstructing extensive soft-plate defects. This method is simple and
achieves reproducible results with limited donor-site morbidity. (c) 2015 Wiley
Periodicals, Inc. Microsurgery 36:291-296, 2016.
PMID- 26419934
TI - A systematic review of community-to-facility neonatal referral completion rates
in Africa and Asia.
AB - BACKGROUND: An estimated 2.8 million neonatal deaths occur annually worldwide.
The vulnerability of newborns makes the timeliness of seeking and receiving care
critical for neonatal survival and prevention of long-term sequelae. To better
understand the role active referrals by community health workers play in neonatal
careseeking, we synthesize data on referral completion rates for neonates with
danger signs predictive of mortality or major morbidity in low- and middle-income
countries. METHODS: A systematic review was conducted in May 2014 of the
following databases: Medline-PubMed, Embase, and WHO databases. We also searched
grey literature. In addition, an investigator group was established to identify
unpublished data on newborn referral and completion rates. Inquiries were made to
the network of research groups supported by Save the Children's Saving Newborn
Lives project and other relevant research groups. RESULTS: Three Sub-Saharan
African and five South Asian studies reported data on community-to-facility
referral completion rates. The studies varied on factors such as referral rates,
the assessed danger signs, frequency of home visits in the neonatal period, and
what was done to facilitate referrals. Neonatal referral completion rates ranged
from 34 to 97 %, with the median rate of 74 %. Four studies reported data on the
early neonatal period; early neonatal completion rates ranged from 46 to 97 %,
with a median of 70 %. The definition of referral completion differed by studies,
in aspects such as where the newborns were referred to and what was considered
timely completion. CONCLUSIONS: Existing literature reports a wide range of
neonatal referral completion rates in Sub-Saharan Africa and South Asia following
active illness surveillance. Interpreting these referral completion rates is
challenging due to the great variation in study design and context. Often, what
qualifies as referral and/or referral completion is poorly defined, which makes
it difficult to aggregate existing data to draw appropriate conclusions that can
inform programs. Further research is necessary to continue highlighting ways for
programs, governments, and policymakers to best aid families in low-resource
settings in protecting their newborns from major health consequences.
PMID- 26419936
TI - Self-Assembly of Tetraphenylalanine Peptides.
AB - Three different tetraphenylalanine (FFFF) based peptides that differ at the N-
and C-termini have been synthesized by using standard procedures to study their
ability to form different nanoassemblies under a variety of conditions. The FFFF
peptide assembles into nanotubes that show more structural imperfections at the
surface than those formed by the diphenylalanine (FF) peptide under the same
conditions. Periodic DFT calculations (M06L functional) were used to propose a
model that consists of three FFFF molecules defining a ring through head-to-tail
NH3(+)???(-)OOC interactions, which in turn stack to produce deformed channels
with internal diameters between 12 and 16 A. Depending on the experimental
conditions used for the peptide incubation, N-fluorenylmethoxycarbonyl (Fmoc)
protected FFFF self-assembles into a variety of polymorphs: ultra-thin
nanoplates, fibrils, and star-like submicrometric aggregates. DFT calculations
indicate that Fmoc-FFFF prefers a parallel rather than an antiparallel beta-sheet
assembly. Finally, coexisting multiple assemblies (up to three) were observed for
Fmoc-FFFF-OBzl (OBzl = benzyl ester), which incorporates aromatic protecting
groups at the two peptide terminals. This unusual and noticeable feature is
attributed to the fact that the assemblies obtained by combining the Fmoc and
OBzl groups contained in the peptide are isoenergetic.
PMID- 26419937
TI - An integrated dose-finding tool for phase I trials in oncology.
AB - In the past 25 years, the 3+3 design has been the most popular approach for
planning phase I dose-finding trials in oncology. During the same time period,
major development of more efficient model-based designs has been made by
statistical researchers aiming to improve the clinical practice of dose finding
in oncology. Despite the effort, 3+3 is still the most frequently used designs in
practice. Part of the reason is due to the lack of software tools that allow
comparison of different designs, including 3+3 and other model-based methods, in
a head-to-head and easy-to-use fashion. To this end, we introduce NextGen-DF, a
next-generation tool for designing oncology dose-finding trials that allows for
construction, comparison, and calibration of multiple designs via internet, in
real time, and independent of computer operating systems. Through NextGen-DF, we
present massive and user-generated comparison results based on over 4 million
simulated trials, which clearly indicate the inferiority of 3+3. To our
knowledge, the reported crowd-sourcing results are the largest and most objective
comparison across major dose-finding methods to date. NextGen-DF is expected to
improve patient care and drug development by providing safer and more efficient
designs for phase I oncology trials. NextGen-DF is available at
www.compgenome.org/NGDF.
PMID- 26419943
TI - Graduate nurses' knowledge of the functions and limitations of pulse oximetry.
AB - AIMS AND OBJECTIVES: To examine nursing graduates' knowledge of functions and
limitations of pulse oximetry. BACKGROUND: Pulse oximetry is a technology
ubiquitous in its use in modern clinical settings. Although the technology's
ability to accurately reflect hypoxaemia in patients has been established, its
contribution to improving patient outcomes is less certain. In addition,
experienced nurses have previously demonstrated poor understanding of the
limitations of the technology. Pregraduate education has been identified as a
potential source of knowledge deficit and has been recommended by authors as an
important target of investigation. DESIGN: Cross-sectional, comparative,
multicentre study. METHOD: A previously published and validated tool was used
with the addition of eight clinical scenario questions which were validated by an
expert panel. Convenience sampling was used to select participants to form one
cohort of newly graduated nurses (Cohort 1: n = 210) and a second cohort of
nurses completing their intensive postgraduate clinical year (Cohort 2: n = 97).
RESULTS: Significant deficits relating to the theoretical factors that affect
pulse oximetry application and interpretation were identified. Results suggest
some knowledge is negatively correlated with clinical experience and that
pregraduate university education appears to influence the ability to effectively
apply pulse oximetry knowledge to clinical scenarios. CONCLUSIONS: This study
provides insight into pulse oximetry knowledge acquisition and deficits of
graduate nurses which may inform pre- and postgraduate nurse education. In
particular, it suggests that some pulse oximetry knowledge and clinical
application of knowledge is not enhanced by clinical experience but rather is
currently gained through pregraduate experiences. RELEVANCE TO CLINICAL PRACTICE:
Inappropriate utilisation and interpretation of pulse oximetry places patients at
risk of mismanagement and undetected deterioration. Improvement in pregraduate
education around the appropriate use of pulse oximetry may reduce clinical costs,
reduce incidents of failure to rescue and improve patient outcomes.
PMID- 26419944
TI - North Americans are eating more fat and less carbohydrate, study finds.
PMID- 26419938
TI - A ROS-Activatable Agent Elicits Homologous Recombination DNA Repair and
Synergizes with Pathway Compounds.
AB - We designed ROS-activated cytotoxic agents (RACs) that are active against AML
cancer cells. In this study, the mechanism of action and synergistic effects
against cells coexpressing the AML oncogenes MLL-AF9 fusion and FLT3-ITD were
investigated. One RAC (RAC1) had an IC50 value of 1.8+/-0.3 MUm, with ninefold
greater selectivity for transformed cells compared to untransformed cells.
Treatment induced DNA strand breaks, apoptosis, and cell cycle arrest. Proteomics
and transcriptomics revealed enhanced expression of the pentose phosphate
pathway, DNA repair, and pathways common to cell stress. Western blotting
confirmed repair by homologous recombination. Importantly, RAC1 treatment was
synergistic in combination with multiple pathway-targeting therapies in AML cells
but less so in untransformed cells. Together, these results demonstrate that RAC1
can selectively target poor prognosis AML and that it does so by creating DNA
double-strand breaks that require homologous recombination.
PMID- 26419945
TI - Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II
activity in human hepatic cells.
AB - Ginkgo biloba leaf extract has been shown to increase the incidence in liver
tumors in mice in a 2-year bioassay conducted by the National Toxicology Program.
In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of
its constituents were evaluated in human hepatic HepG2 cells and the underlying
mechanism was determined. A molecular docking study revealed that quercetin, a
flavonoid constituent of Ginkgo biloba, showed a higher potential to interact
with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents;
this in silico prediction was confirmed by using a biochemical assay to study
Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the
induction of gamma-H2A.X, quercetin, followed by keampferol and isorhamnetin,
appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II
knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin
was dramatically decreased, indicating that DNA damage is directly associated
with Topo II. DNA damage was also observed when cells were treated with
commercially available Ginkgo biloba extract product. Our findings suggest that
Ginkgo biloba leaf extract- and quercetin-induced in vitro genotoxicity may be
the result of Topo II inhibition.
PMID- 26419946
TI - Cell Magnetic Targeting System for Repair of Severe Chronic Osteochondral Defect
in a Rabbit Model.
AB - The aim of this study was to investigate a cell delivery system for repair of
severe chronic osteochondral defects using magnetically labeled mesenchymal stem
cells (m-MSCs), with the aid of an external magnetic device, through the
accumulation of a small number of m-MSCs into a desired area and to detect the
suitable number of autologous m-MSCs needed for repair of the defect. Twenty-six
male Japanese white rabbits aged 6 months were used. An osteochondral defect was
created bilaterally at the weight-bearing surface of the medial femoral condyle
of the rabbits' knees (3 mm diameter; 4 mm depth). At 4 weeks after creation of
the defect, autogenic transplantation of the m-MSCs into the defect area was
performed, followed by 10-min exposure to an external magnetic device, where
animals were divided into four groups: high (1 * 10(6) m-MSCs), medium (2 * 10(5)
m-MSCs), low (4 * 10(4) m-MSCs), and control (PBS injection). At 4 and 12 weeks
posttransplantation of m-MSCs, repaired tissue was assessed histologically using
the Fortier score with toluidine blue staining. Transplantation of a low number
of m-MSCs was not enough to improve osteogenesis and chondrogenesis, but the
medium and high groups improved repair of the chronic defect with chondrogenic
tissues and showed histologically significantly better results than the control
and low groups. The use of a magnetic targeting system for delivering m-MSCs has
the potential to overcome the clinical hurdles for repair of the severe chronic
osteochondral defect. Furthermore, this system is predicted to produce good
clinical outcomes for humans, not only to repair osteochondral defects but also
to repair a variety of damaged tissues.
PMID- 26419947
TI - Reference ranges of hematology and lymphocyte subsets in healthy Korean native
cattle (Hanwoo) and Holstein dairy cattle.
AB - There are no accurate reference ranges for hematology parameters and lymphocyte
subsets in Korean native beef cattle (Hanwoo). This study was performed to
establish reliable reference ranges of hematology and lymphocyte subsets using a
large number of Hanwoo cattle (n = 350) and to compare differences between Hanwoo
and Holstein dairy cattle (n = 334). Additionally, age-related changes in
lymphocyte subsets were studied. Bovine leukocyte subpopulation analysis was
performed using mono or dual color flow cytometry. The leukocyte subpopulations
investigated in healthy cattle included: CD2(+) cells, sIgM(+) cells, MHC class
II(+) cells, CD3(+) CD4(+) cells, CD3(+) CD8(+) cells, and WC1(+) cells. Although
Hanwoo and Holstein cattle are the same species, results showed several
differences in hematology and lymphocyte subsets between Hanwoo and Holstein
cattle. This study is the first report to establish reference ranges of
hematology and lymphocyte subsets in adult Hanwoo cattle.
PMID- 26419949
TI - Subducting seamounts control interplate coupling and seismic rupture in the 2014
Iquique earthquake area.
AB - To date, the parameters that determine the rupture area of great subduction zone
earthquakes remain contentious. On 1 April 2014, the Mw 8.1 Iquique earthquake
ruptured a portion of the well-recognized northern Chile seismic gap but left
large highly coupled areas un-ruptured. Marine seismic reflection and swath
bathymetric data indicate that structural variations in the subducting Nazca
Plate control regional-scale plate-coupling variations, and the limited extent of
the 2014 earthquake. Several under-thrusting seamounts correlate to the southward
and up-dip arrest of seismic rupture during the 2014 Iquique earthquake, thus
supporting a causal link. By fracturing of the overriding plate, the subducting
seamounts are likely further responsible for reduced plate-coupling in the
shallow subduction zone and in a lowly coupled region around 20.5 degrees S. Our
data support that structural variations in the lower plate influence coupling and
seismic rupture offshore Northern Chile, whereas the structure of the upper plate
plays a minor role.
PMID- 26419948
TI - Transcriptomic changes following synthesis of a Populus full-sib diploid and
allotriploid population with different heterozygosities driven by three types of
2n female gamete.
AB - Diploid gametes are usually applied to produce triploids of Populus [originating
from first-division restitution (FDR), second-division restitution (SDR), and
postmeiotic restitution (PMR) 2n eggs]. Three types of 2n gametes transmitted
different parental heterozygosities in Populus. Failed spindle formation and no
chromosomal separation to opposite poles during meiosis I mean that FDR 2n
gametes carry nonsister chromatids that are potentially heterozygous. By
contrast, SDR 2n gametes result from failed sister chromatid separation in
meiosis II, and therefore, they carry sister chromatid that are potentially
homozygous. Completely homozygous 2n gametes can arise from the PMR mechanism.
The alteration of gene expression resulting from allopolyploidization is a
prominent feature in plants. We compared gene expression in the full-sib progeny
of three allotriploid Populus populations (triploid-F, triploid-S, and triploid
P) with that in its parent species, and their full-sib diploid F1 hybrid. Genome
wide expression level dominance was biased toward the maternal in the diploid F1
hybrid and three allotriploid populations, whereas our data indicated important,
but different, effects of the transmission of different heterozygosity by 2n
female gametes in the expression patterns of allopolyploids. Because of the
higher level of heterozygosity, the triploids had higher rates of non-additive
and transgressive expression patterns in the triploid-F than in triploid-S and
triploid-P. Compared with diploid F1, about 30-fold more genes (251) were
differently expressed in the triploid-F than in the triploid-S (9) and triploid-P
(8), respectively. These findings indicate that hybridization and
polyploidization have immediate and distinct effects on the large-scale patterns
of gene expression, and different effects on the transmission of heterozygosity
by three 2n female gametes.
PMID- 26419950
TI - Ultralow-threshold multiphoton-pumped lasing from colloidal nanoplatelets in
solution.
AB - Although multiphoton-pumped lasing from a solution of chromophores is important
in the emerging fields of nonlinear optofluidics and bio-photonics,
conventionally used organic dyes are often rendered unsuitable because of
relatively small multiphoton absorption cross-sections and low photostability.
Here, we demonstrate highly photostable, ultralow-threshold multiphoton-pumped
biexcitonic lasing from a solution of colloidal CdSe/CdS nanoplatelets within a
cuvette-based Fabry-Perot optical resonator. We find that colloidal nanoplatelets
surprisingly exhibit an optimal lateral size that minimizes lasing threshold.
These nanoplatelets possess very large gain cross-sections of 7.3 * 10(-14) cm(2)
and ultralow lasing thresholds of 1.2 and 4.3 mJ cm(-2) under two-photon
(lambdaexc=800 nm) and three-photon (lambdaexc=1.3 MUm) excitation, respectively.
The highly polarized emission from the nanoplatelet laser shows no significant
photodegradation over 10(7) laser shots. These findings constitute a more
comprehensive understanding of the utility of colloidal semiconductor
nanoparticles as the gain medium in high-performance frequency-upconversion
liquid lasers.
PMID- 26419951
TI - Opportunities and challenges of integrating ecological restoration into
assessment and management of contaminated ecosystems.
AB - Ecosystem restoration planning near the beginning of the site assessment and
management process ("early integration") involves consideration of restoration
goals from the outset in developing solutions for contaminated ecosystems. There
are limitations to integration that stem from institutional barriers, few
successful precedents, and limited availability of guidance. Challenges occur in
integrating expertise from various disciplines and multiple, sometimes divergent
interests and goals. The more complex process can result in timing, capacity,
communication, and collaboration challenges. On the other hand, integrating the 2
approaches presents new and creative opportunities. For example, integration
allows early planning for expanding ecosystem services on or near contaminated
lands or waters that might otherwise have been unaddressed by remediation alone.
Integrated plans can explicitly pursue ecosystem services that have market value,
which can add to funds for long-term monitoring and management. Early integration
presents opportunities for improved and productive collaboration and coordination
between ecosystem restoration and contaminant assessment and management. Examples
exist where early integration facilitates liability resolution and generates
positive public relations. Restoration planning and implementation before the
completion of the contaminated site assessment, remediation, or management
process ("early restoration") can facilitate coordination with offsite
restoration options and a regional approach to restoration of contaminated
environments. Integration of performance monitoring, for both remedial and
restoration actions, can save resources and expand the interpretive power of
results. Early integration may aid experimentation, which may be more feasible on
contaminated lands than in many other situations. The potential application of
concepts and tools from adaptive management is discussed as a way of avoiding
pitfalls and achieving benefits in early integration. In any case, there will be
challenges with early integration of restoration concepts for contaminated
ecosystems, but the benefits are likely to outweigh them.
PMID- 26419953
TI - Nitrogen-doped graphene network supported copper nanoparticles encapsulated with
graphene shells for surface-enhanced Raman scattering.
AB - In this study, we demonstrated nitrogen-doped graphene network supported few
layered graphene shell encapsulated Cu nanoparticles (NPs) (Cu@G-NGNs) as a
sensing platform, which were constructed by a simple and scalable in situ
chemical vapor deposition (CVD) technique with the assistance of a self-assembled
three-dimensional (3D) NaCl template. Compared with pure Cu NPs and graphene
decorated Cu NPs, the graphene shells can strengthen the plasmonic coupling
between graphene and Cu, thereby contributing to an obvious improvement in the
local electromagnetic field that was validated by finite element numerical
simulations, while the 3D nitrogen-doped graphene walls with a large surface area
facilitated molecule adsorption and the doped nitrogen atoms embedded in the
graphene lattice can reduce the surface energy of the system. With these merits,
a good surface enhanced Raman spectroscopy (SERS) activity of the 3D Cu@G-NGN
painting film on glass was demonstrated using rhodamine 6G and crystal violet as
model analytes, exhibiting a satisfactory sensitivity, reproducibility and
stability. As far as we know, this is the first report on the in situ synthesis
of nitrogen-doped graphene/copper nanocomposites and this facile and low-cost Cu
based strategy tends to be a good supplement to Ag and Au based substrates for
SERS applications.
PMID- 26419952
TI - Post-chikungunya chronic arthralgia: Results from a retrospective follow-up study
of 131 cases in Tolima, Colombia.
PMID- 26419954
TI - Fabrication of Pd Nanoparticles Embedded C@Fe3O4 Core-Shell Hybrid Nanospheres:
An Efficient Catalyst for Cyanation in Aryl Halides.
AB - Isolated chemical reactors were fabricated by integrating catalytically active
sites (Pd) with magnetic functionality (Fe3O4) along with carbon while preserving
the constituents functional properties to realize the structure-property
relationship of Pd by comparing the catalytic activity of spherical Pd NPs with
cubical Pd NPs for cyanation in aryl halides using K4[Fe(CN)6] as a green
cyanating agent to yield corresponding nitriles. The superior catalytic
reactivity of the cubical Pd NPs is attributed to the larger number of {100}
surface facets. The TEM images of reused catalyst shows the change in structure
from cubical to spherical nanoparticles, attributed to the efficient leaching
susceptibility of Pd {100} surface facets. The cubical Pd NPs on carbon@Fe3O4 is
attractive in view of its high catalytic efficiency, easy synthesis, magnetic
separability, environmental friendliness, high stability, gram scale
applicability, and reusability.
PMID- 26419956
TI - Acetabular dysplasia may be related to global joint hyperlaxity.
AB - PURPOSE: Some patients with shoulder laxity complain of coxalgia without a
history of trauma. We hypothesised that patients who have recurrent shoulder
instability accompanied with generalised joint hyperlaxity tend to have
acetabular dysplasia. METHODS: Pelvic radiographs of 26 young patients with
hyperlaxity who had shoulder instability complaints without any history of hip
joint trauma were evaluated by measuring their centre-edge angle (CEA) and
acetabular angle (AA). In addition, Beighton generalised joint laxity tests were
performed. All of the patients had shoulder pain and instability accompanied with
hyperlaxity. We performed magnetic resonance imaging examination to show SLAP
Bankart lesions and pelvis anteroposterior X-rays to detect acetabular dysplasia.
RESULTS: The average age of the study group was 26 +/- 8.03 years (13-39). Six
patients were female and 20 were male. When CEA (<22.6 degrees) was used as a
criterion for acetabular dysplasia, the dysplasia rate of our patient group was
3.84 % for the right hip, 3.84 % for the left hip and 3.84 % overall. When AA
(>42.2 degrees) was used as the dysplasia criterion, the dysplasia rate of
patient group was 30.76 % for the right hip, 57.69 % for the left hip and 57.69 %
overall. CONCLUSIONS: CEA values were significantly lower (p = 0.009) and AA
values were significantly higher (p < 0.001) in our study group than the
previously-reported average values of the Turkish population. We think that
acetabular dysplasia is more frequent in patients with hyperlaxity; further
studies are needed to test this idea.
PMID- 26419957
TI - Midterm clinical results of osteochondral autograft transplantation for advanced
stage Freiberg disease.
AB - PURPOSE: We aimed to evaluate the midterm clinical results of osteochondral
autograft transplantation (OAT) for advanced stage Freiberg disease. METHODS:
This study included consecutive patients who underwent OAT for advanced stage
Freiberg disease and were followed postoperatively for more than five years. In
all cases, the autograft was harvested from the ipsilateral knee joint. Clinical
evaluation was performed based on the American Orthopaedic Foot and Ankle Society
Lesser Metatarsophalangeal-Interphalangeal Scale (AOFAS) score and visual
analogue scale (VAS) score, which were done pre-operatively and at the most
recent follow-up. Radiological evaluation was performed at two years after the
operation. Furthermore, the most recent six patients underwent magnetic resonance
imaging (MRI) five years after the operation to assess the configuration of the
articular surface. RESULTS: A total of 13 patients (all female; mean age 16.7
years; range 10-38 years) were included and followed up for a mean duration of
67.2 months (range 60-100 months). The mean AOFAS significantly improved from a
score of 66.9 +/- 5.3 (range 59-77) to 93.0 +/- 7.6 (range 82-100) (p < 0.0001).
Likewise, the mean VAS significantly improved from a score of 72.7 +/- 10.3
(range 60-90) to 7.8 +/- 7.2 (range 0-20) (p < 0.0001). Radiographs at two years
after the operation revealed no osteoarthritic change in all cases. MRI at five
years after the operation showed consolidation of the transplanted autograft and
smooth configuration of the articular surface in the six cases. CONCLUSIONS: OAT
may be effective for advanced stage Freiberg disease. Further studies are
necessary before this technique can become the standard operative treatment.
PMID- 26419955
TI - Analysis of Proteins That Rapidly Change Upon Mechanistic/Mammalian Target of
Rapamycin Complex 1 (mTORC1) Repression Identifies Parkinson Protein 7 (PARK7) as
a Novel Protein Aberrantly Expressed in Tuberous Sclerosis Complex (TSC).
AB - Many biological processes involve the mechanistic/mammalian target of rapamycin
complex 1 (mTORC1). Thus, the challenge of deciphering mTORC1-mediated functions
during normal and pathological states in the central nervous system is
challenging. Because mTORC1 is at the core of translation, we have investigated
mTORC1 function in global and regional protein expression. Activation of mTORC1
has been generally regarded to promote translation. Few but recent works have
shown that suppression of mTORC1 can also promote local protein synthesis.
Moreover, excessive mTORC1 activation during diseased states represses basal and
activity-induced protein synthesis. To determine the role of mTORC1 activation in
protein expression, we have used an unbiased, large-scale proteomic approach. We
provide evidence that a brief repression of mTORC1 activity in vivo by rapamycin
has little effect globally, yet leads to a significant remodeling of synaptic
proteins, in particular those proteins that reside in the postsynaptic density.
We have also found that curtailing the activity of mTORC1 bidirectionally alters
the expression of proteins associated with epilepsy, Alzheimer's disease, and
autism spectrum disorder-neurological disorders that exhibit elevated mTORC1
activity. Through a protein-protein interaction network analysis, we have
identified common proteins shared among these mTORC1-related diseases. One such
protein is Parkinson protein 7, which has been implicated in Parkinson's disease,
yet not associated with epilepsy, Alzheimers disease, or autism spectrum
disorder. To verify our finding, we provide evidence that the protein expression
of Parkinson protein 7, including new protein synthesis, is sensitive to mTORC1
inhibition. Using a mouse model of tuberous sclerosis complex, a disease that
displays both epilepsy and autism spectrum disorder phenotypes and has overactive
mTORC1 signaling, we show that Parkinson protein 7 protein is elevated in the
dendrites and colocalizes with the postsynaptic marker postsynaptic density-95.
Our work offers a comprehensive view of mTORC1 and its role in regulating
regional protein expression in normal and diseased states.
PMID- 26419958
TI - Mutual positive effects between shrubs in an arid ecosystem.
AB - One-way facilitation in plants has been found in many harsh environments and
their role as structural forces governing species composition in plant
communities is now well established. However, reciprocal positive effects
benefiting two interacting species have seldom been reported and, in recent
reviews, conceptually considered merely as facilitation when in fact there is
room for adaptive strategies and evolutionary responses. We tested the existence
of such reciprocal positive effects in an arid environment in SE Spain using
spatial pattern analysis, a species removal experiment, and a natural experiment.
We found that the spatial association between Maytenus senegalensis and Whitania
frutescens, two shrub species of roughly similar size intimately interacting in
our community, resulted in mutual benefit for both species. Benefits included
improved water relations and nutritional status and protection against browsing,
and did occur despite simultaneous competition for resources. Our data suggest
two-way facilitation or, rather, a facultative mutualism among higher plant
species, a process often overlooked which could be a main driver of plant
community dynamics allowing for evolutionary processes.
PMID- 26419960
TI - Subacute CNS Demyelination after Treatment with Nivolumab for Melanoma.
AB - Immunotherapy with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen
4 (CTLA-4) or programmed cell death 1 (PD-1) has improved the survival of
patients with metastatic melanoma. These agents carry a certain risk of adverse
immune-related events. We present a patient with widely metastatic melanoma who
was initially treated with ipilimumab and subsequently with nivolumab. After four
infusions of nivolumab, he developed subacute multifocal central nervous system
(CNS) demyelination. Nivolumab was discontinued and, despite immunosuppressive
therapy, the largest lesion progressed significantly, whereas another lesion
showed radiographic improvement. After further progression, the patient succumbed
to his CNS lesions 4 months later. Autopsy revealed extensive demyelination, a
mild multifocal T-cell-rich perivascular lymphoid infiltrate, abundant
macrophages, and necrosis. There was no metastatic melanoma in the brain. CNS
demyelination has not been described in association with nivolumab. We
hypothesize that the combination therapy of ipilimumab and subsequent nivolumab
accounted for the severity of the demyelinating process in this patient. This
case, with comprehensive clinical, molecular, and neuropathologic
characterization, illustrates the need for awareness of these potential CNS
complications with the use of multiple checkpoint inhibitors.
PMID- 26419959
TI - MicroRNA MIR21 and T Cells in Colorectal Cancer.
AB - The complex interactions between colorectal neoplasia and immune cells in the
tumor microenvironment remain to be elucidated. Experimental evidence suggests
that microRNA MIR21 (miR-21) suppresses antitumor T-cell-mediated immunity. Thus,
we hypothesized that tumor MIR21 expression might be inversely associated with T
cell density in colorectal carcinoma tissue. Using 538 rectal and colon cancer
cases from the Nurses' Health Study and the Health Professionals Follow-up Study,
we measured tumor MIR21 expression by a quantitative reverse-transcription PCR
assay. Densities of CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cells in
tumor tissue were determined by tissue microarray immunohistochemistry and
computer-assisted image analysis. Ordinal logistic regression analysis was
conducted to assess the association of MIR21 expression (ordinal quartiles as a
predictor variable) with T-cell density (ordinal quartiles as an outcome
variable), adjusting for tumor molecular features, including microsatellite
instability; CpG island methylator phenotype; KRAS, BRAF, and PIK3CA mutations;
and LINE-1 methylation. We adjusted the two-sided alpha level to 0.012 for
multiple hypothesis testing. Tumor MIR21 expression was inversely associated with
densities of CD3(+) and CD45RO(+) cells (Ptrend < 0.0005). The multivariate odds
ratio of the highest versus lowest quartile of MIR21 for a unit increase in
quartile categories of CD3(+) or CD45RO(+) cells was 0.44 [95% confidence
interval (CI), 0.28 to 0.68] or 0.41 (95% CI, 0.26-0.64), respectively. Our data
support a possible role of tumor epigenetic deregulation by noncoding RNA in
suppressing the antitumor T-cell-mediated adaptive immune response and suggest
MIR21 as a potential target for immunotherapy and prevention in colorectal
cancer.
PMID- 26419962
TI - On the thermodynamically stable amorphous phase of polymer-derived silicon
oxycarbide.
AB - A model for the thermodynamic stability of amorphous silicon oxycarbide (SiCO) is
presented. It builds upon the reasonably accepted model of SiCO which is
conceived as a nanodomain network of graphene. The domains are expected to be
filled with SiO2 molecules, while the interface with graphene is visualized to
contain mixed bonds described as Si bonded to C as well as to O atoms. Normally
these SiCO compositions would be expected to crystallize. Instead, calorimetric
measurements have shown that the amorphous phase is thermodynamically stable. In
this article we employ first-principles calculations to estimate how the
interfacial energy of the graphene networks is favorably influenced by having
mixed bonds attached to them. We analyze the ways in which this reduction in
interfacial energy can stabilize the amorphous phase. The approach highlights how
density functional theory computations can be combined with the classical
analysis of phase transformations to explain the behavior of a complex material.
In addition we discover a two-dimensional lattice structure, with the composition
Si2C4O3 that is constructed from a single layer of graphene congruent with
silicon and oxygen bonds on either side.
PMID- 26419963
TI - Two-stage, acetic acid-aqueous ammonia, fractionation of empty fruit bunches for
increased lignocellulosic biomass utilization.
AB - Fractionation of EFB was conducted in two consecutive steps using a batch
reaction system: hemicellulose hydrolysis using acetic acid (AA; 3.0-7.0 wt.%) at
170-190 degrees C for 10-20 min in the first stage, and lignin solubilization
using ammonium hydroxide (5-20 wt.%) at 140-220 degrees C for 5-25 min in the
second stage. The two-stage process effectively fractionated empty fruit bunches
(EFB) in terms of hemicellulose hydrolysis (53.6%) and lignin removal (59.5%).
After the two-stage treatment, the fractionated solid contained 65.3% glucan.
Among three investigated process parameters, reaction temperature and ammonia
concentration had greater impact on the delignification reaction in the second
stage than reaction time. The two-stage fractionation processing improved the
enzymatic digestibility to 72.9% with 15 FPU of cellulase/g of glucan
supplemented with 70 pNPG of beta-glycosidase (Novozyme 188)/g-glucan, which was
significantly enhanced from the equivalent digestibility of 28.3% for untreated
EFB and 45.7% for AAH-fractionated solid.
PMID- 26419961
TI - Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors.
AB - Non-small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the
anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine kinase
inhibitors (TKI), but the treatment is successful for only a limited amount of
time; most patients experience a relapse due to the development of drug
resistance. Here, we show that a vaccine against ALK induced a strong and
specific immune response that both prophylactically and therapeutically impaired
the growth of ALK-positive lung tumors in mouse models. The ALK vaccine was
efficacious also in combination with ALK TKI treatment and significantly delayed
tumor relapses after TKI suspension. We found that lung tumors containing ALK
rearrangements induced an immunosuppressive microenvironment, regulating the
expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression
reduced ALK vaccine efficacy, which could be restored by administration of anti
PD-1 immunotherapy. Thus, combinations of ALK vaccine with TKIs and immune
checkpoint blockade therapies might represent a powerful strategy for the
treatment of ALK-driven NSCLC.
PMID- 26419964
TI - Rapid and solvent-saving liquefaction of woody biomass using microwave-ultrasonic
assisted technology.
AB - A novel process to rapidly liquefy sawdust using reduced quantities of solvent,
was successfully carried out via microwave-ultrasonic assisted technology (MUAT)
in a sulphuric acid/polyethylene glycol 400-glycerol catalytic system. The
influences of some key parameters on the liquefaction yield were investigated.
The results showed that compared with traditional liquefaction, the introduction
of MUAT allowed the solvent dosage to be halved and shortened the liquefaction
time from 60 to 20 min. The liquefaction yield reached 91% under the optimal
conditions. However, the influence on the yield of some parameters such as
catalyst concentration, was similar to that of traditional liquefaction,
indicating that the application of MUAT possibly only intensified heat and mass
transfer rather than altering either the degradation mechanism or pathway. The
introduction of MUAT as a process intensification technology has good industrial
application potential for woody biomass liquefaction.
PMID- 26419965
TI - Clinically Confirmed Stroke With Negative Diffusion-Weighted Imaging Magnetic
Resonance Imaging: Longitudinal Study of Clinical Outcomes, Stroke Recurrence,
and Systematic Review.
AB - BACKGROUND AND PURPOSE: We sought to establish whether the presence (versus
absence) of a lesion on magnetic resonance imaging (MRI) with diffusion weighting
(DWI-MRI) at presentation with acute stroke is associated with worse clinical
outcomes at 1 year. METHODS: We recruited consecutive patients with a
nondisabling ischemic stroke and performed DWI-MRI. Patients were followed up at
1 year to establish stroke recurrence (clinical or on MRI), cognitive impairment
(Addenbrooke Cognitive Assessment Revised,<88) and modified Rankin Scale.
RESULTS: A median of 4 days post stroke, one third (76/264; 29%) of patients did
not have a DWI lesion (95% confidence interval, 23%-35%). There was no
statistically significant difference between those with and without a DWI lesion
with respect to age or vascular risk factors. Patients without a lesion were more
likely to be women or have previous stroke. At 1 year, 11 of 76 (14%) patients
with a DWI-negative index stroke had a clinical diagnosis of recurrent stroke or
transient ischemic attack, 33% had cognitive impairment (Addenbrooke Cognitive
Assessment Revised<88), and 40% still had modified Rankin Scale>1, no different
from DWI-positive patients; DWI-positive patients were more likely to have a new
lesion on MRI (14%), symptomatic or asymptomatic, than DWI-negative patients (2%;
P=0.02). Our data were consistent with 6 other studies (total n=976), pooled
proportion of DWI-negative patients was 21% (95% confidence interval, 12%-32%).
CONCLUSIONS: Nearly one third of patients with nondisabling stroke do not have a
relevant lesion on acute DWI-MRI. Patients with negative DWI-MRI had no better
prognosis than patients with a lesion. DWI-negative stroke patients should
receive secondary prevention.
PMID- 26419966
TI - Reflux of Anterior Spinal Artery Predicts Recurrent Posterior Circulation Stroke
in Bilateral Vertebral Artery Disease.
AB - BACKGROUNDS AND PURPOSE: Predictive value of reflux of anterior spinal artery for
recurrent posterior circulation ischemia in bilateral vertebral arteries steno
occlusive disease was evaluated. METHODS: We retrospectively reviewed 55 patients
with symptomatic posterior circulation stroke caused by bilateral stenotic (>70%)
lesions of the vertebral artery. We investigated any correlation of clinical and
angiographic characteristics including collateral flow patterns, with recurrent
stroke. Risk factors for poor 3-month functional outcome were also evaluated.
RESULTS: Recurrent posterior circulation stroke was observed in 15 (27.3%)
patients. Multivariable analysis using Cox proportional hazards model showed
anterior spinal artery reflux as a significant risk factor for stroke recurrence
(adjusted hazard ratio, 19.3 [95% confidence interval, 5.35-69.9]; P<0.001).
Anterior spinal artery reflux was also correlated with poor functional outcome
(modified Rankin Scale score, 3-6; adjusted odds ratio, 7.41 [95% confidence
interval, 1.24-44.4]; P=0.028). CONCLUSIONS: In patients with symptomatic
bilateral vertebral artery occlusive disease, anterior spinal artery reflux
predicted recurrent posterior circulation stroke and poor functional outcome.
PMID- 26419967
TI - Location, Infarct Load, and 3-Month Outcomes of Delayed Cerebral Infarction After
Aneurysmal Subarachnoid Hemorrhage.
AB - BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage is a serious disease
with high case fatality and morbidity. Delayed cerebral infarction (DCI) is an
important surrogate marker. How location and infarct load affected outcomes was
unclear. We aimed to assess the effects of load and location of DCI on outcomes
of aneurysmal subarachnoid hemorrhage at 3 months. METHODS: We prospectively
enrolled patients with subarachnoid hemorrhage presenting to an academic
neurosurgical unit in Hong Kong during a 3-year period. DCI was defined by new
hypoattenuation on computed tomography at 4 to 6 weeks, which was not present in
the postaneurysm-treatment computed tomography at 24 to 48 hours. DCI was
assessed for location according to cerebral artery territories and load
semiquantitatively. Cognitive and functional outcome assessments were carried out
3 months after ictus. RESULTS: One hundred twenty-six patients with subarachnoid
hemorrhage consented for this study. DCI occurred in 56 (44%) patients and was
associated with poorer cognitive and functional outcomes (Montreal Cognitive
Assessment, Mini-Mental State Examination, modified Rankin Scale, and Lawton
Instrumental Activity of Daily Living) at 3 months. In patients with DCI, the
presence of perforator zone infarct was associated with poorer cognitive and
functional outcomes, and cortical middle cerebral artery infarct was associated
with poorer modified Rankin Scale. After adjustment for age, admission World
Federation of Neurosurgical Societies Grade and mode of aneurysm treatment, both
middle cerebral artery cortical infarct load and perforator infarct load were
independently associated with poor cognitive outcomes (Montreal Cognitive
Assessment and Mini-Mental State Examination) and modified Rankin Scale.
CONCLUSIONS: Middle cerebral artery cortical and perforator zone infarct loads
are potential surrogate marker to assess the severity of delayed cerebral
ischemia.
PMID- 26419968
TI - Differences Between US and UK Adults in Stroke Preparedness: Evidence From
Parallel Population-Based Community Surveys.
AB - BACKGROUND AND PURPOSE: Although time-dependent treatment is available, most
people delay contacting emergency medical services for stroke. Given differences
in the healthcare system and public health campaigns, exploring between-country
differences in stroke preparedness may identify novel ways to increase acute
stroke treatment. METHODS: A survey was mailed to population-based samples in
Ingham County, Michigan, US (n=2500), and Newcastle upon Tyne, UK (n=2500).
Surveys included stroke perceptions and stroke/nonstroke scenarios to assess
recognition and response to stroke. Between-country differences and associations
with stroke preparedness were examined using t tests and linear mixed models.
RESULTS: Overall response rate was 27.4%. The mean age of participants was 55
years, and 58% were female. US participants were better in recognizing stroke
(70% versus 63%, d=0.27) and were more likely to call emergency medical services
(55% versus 52%, d=0.11). After controlling for demographics and comorbidities,
US participants remained more likely to recognize stroke but were not more likely
to respond appropriately. A greater belief that medical treatment can help with
stroke and understanding of stroke was associated with improved stroke
recognition and response. CONCLUSIONS: Overall, stroke recognition and response
were moderate. US participants were modestly better at recognizing stroke,
although there was little difference in response to stroke. Future stroke
awareness interventions could focus more on stroke outcome expectations and
developing a greater understanding of stroke among the public.
PMID- 26419969
TI - Poor Collateral Circulation Assessed by Multiphase Computed Tomographic
Angiography Predicts Malignant Middle Cerebral Artery Evolution After Reperfusion
Therapies.
AB - BACKGROUND AND PURPOSE: Collateral circulation (CC) has been associated with
recanalization, infarct volume, and clinical outcome in patients undergoing acute
reperfusion therapies. However, its relationship with the development to
malignant middle cerebral artery infarction (mMCAi) has not been evaluated. Our
aim was to determine the impact of CC using multiphase computed tomographic
angiography (during the acute stroke phase in the prediction of mMCAi. METHODS:
Patients with consecutive acute stroke with <4.5 hours who were evaluated for
reperfusion therapies and presented with an M1-MCA or terminal internal carotid
artery occlusion by CTA were included. CC was evaluated on 6 grades by multiphase
CTA according to the University of Calgary CC Scale; CC status was defined as
poor (grades, 0-3) or good (grades, 4-5). The mMCAi was defined according to
clinical and radiological criteria. Recanalization was assessed with transcranial
Doppler at 24 hours and final Thrombolysis in Brain Ischemia score>=2b in
patients undergoing endovascular reperfusion treatment. RESULTS: Eighty-two
patients were included. Mean age was 65.1+/-13.83 years, median baseline National
Institutes of Health Stroke Scale score was 18 (interquartile range, 13-20), and
67.9% M1 and 32.1% terminal internal carotid artery occlusions. Fifty-three
patients received endovascular reperfusion treatment. Fifteen patients developed
mMCAi. In the univariate analysis, patients with mMCAi had lower CC scores (2.29
versus 3.71; P=0.001). Endovascular reperfusion treatment was associated with
lower rate of mMCAi development than only intravenous reperfusion treatment (9.4%
versus 29.6%; P=0.028). Patients with poor CC had higher risk of developing mMCAi
(13% versus 2%; P=0.001). On the multivariate analysis adjusted by age, vessel
occlusion, baseline National Institutes of Health Stroke Scale, and
recanalization, the presence of poor CC by multiphase CTA was the only
independent predictor of mMCAi (P=0.048; odds ratio, 9.72; 95% confidence
interval, 1.387-92.53). CONCLUSIONS: CC assessment by multiphase CTA
independently predicts malignant MCA infarction progression. In patients with
persistent occlusion after reperfusion therapies, the presence of poor CC may
improve the early mMCAi detection and management.
PMID- 26419970
TI - The pathway for serial proton supply to the active site of nitrogenase: enhanced
density functional modeling of the Grotthuss mechanism.
AB - Nitrogenase contains a well defined and conserved chain of water molecules
leading to the FeMo cofactor (FeMo-co, an [Fe7MoCS9] cluster with bidentate
chelation of Mo by homocitrate) that is the active site where N2 and other
substrates are sequentially hydrogenated using multiple protons and electrons.
The function of this chain is proposed to be a proton wire, serially
translocating protons to triply-bridging S3B of FeMo-co, where, concomitant with
electron transfer to FeMo-co, an H atom is generated on S3B. Density functional
simulations of this proton translocation mechanism are reported here, using a
large 269-atom model that includes all residues hydrogen bonded to and
surrounding the water chain, and likely to influence proton transfer: three
carboxylate O atoms of obligatory homocitrate are essential. The mechanism
involves the standard two components of the Grotthuss mechanism, namely H atom
slides that shift H3O(+) from one water site to the next, and HOH molecular
rotations that convert backward (posterior) OH bonds in the water chain to
forward (anterior) OH bonds. The topography of the potential energy surface for
each of these steps has been mapped. H atom slides pass through very short (ca.
2.5 A) O-H-O hydrogen bonds, while HOH rotations involve the breaking of O-HO
hydrogen bonds, and the occurrence of long (up to 3.6 A) separations between
contiguous water molecules. Both steps involve low potential energy barriers, <7
kcal mol(-1). During operation of the Grotthuss mechanism in nitrogenase there
are substantial displacements of water molecules along the chain, occurring as
ripples. These characteristics of the 'Grotthuss two-step', coupled with a
buffering ability of two carboxylate O atoms of homocitrate, and combined with
density functional characterisation of the final proton slide from the ultimate
water molecule to S3B (including electron addition), have been choreographed into
a complete mechanism for serial hydrogenation of FeMo-co. The largest potential
barrier is estimated to be 14 kcal mol(-1). These results are discussed in the
context of reactivity data for nitrogenase, and the occurrence of a comparable
water chain in cytochrome-c oxidase. Further investigation of the low-frequency
conformational dynamics of the nitrogenase proteins, coupling proton transfer
with other events in the nitrogenase cycle, is briefly canvassed.
PMID- 26419971
TI - Pharmacovigilance Considerations for Biosimilars in the USA.
AB - In 2015, five or more biosimilars may be approved in the USA. Because no two
biologic medicines are identical, postapproval safety monitoring will be critical
to detect potential differences in safety signals between a biosimilar, its
reference product, and other biosimilars. Postapproval safety monitoring in the
USA uses two signal detection systems: spontaneous reporting systems (SRSs) and
active surveillance (AS) systems. Both depend on accurate identification of the
specific product(s) dispensed or administered to patients, which may be
compromised when products from multiple manufacturers share common drug
nomenclature or coding. Product identification can present challenges across
different healthcare settings, including inpatient and ambulatory care. Common
oral-dosage drugs are predominantly dispensed directly to patients by
pharmacists, whereas most injectable drugs, including biologics, are administered
to patients by healthcare professionals in outpatient clinics or hospitals. Thus,
the effectiveness of SRS and AS mechanisms in both pharmacy and medical channels
must be given greater consideration as biotechnology matures. In this article, we
describe these systems and their limitations. We identify challenges and
opportunities for product-specific safety surveillance of biologics in both the
pharmacy and medical settings and provide recommendations to improve biologic
safety surveillance under the current and future systems envisioned in the Drug
Quality and Security Act. As biosimilars are integrated into existing
pharmacovigilance systems, distinguishable nonproprietary names and codes for all
biologics, as well as other opportunities to improve traceability (e.g.,
increased use of barcodes), must be considered to ensure patient safety and
confidence in this new class of drugs.
PMID- 26419973
TI - First-principles study of terpyrrole as a potential hydrogen cyanide sensor: DFT
calculations.
AB - The sensitivity of terpyrrole (TPy; used as a polypyrrole model) to toxic
hydrogen cyanide (HCN) adsorption was studied by using DFT to perform geometry
optimization and to calculate the adsorption energy of HCN on TPy as well as
orbital properties. The interaction of terpyrrole with HCN was studied for
different relative orientations of the molecules. The adsorption energy, charge
analysis, and the density of states were used to evaluate the ability of TPy to
sense HCN in these different relative orientations. The adsorption energy was
calculated to be -3.9 and -3.1 kcal mol(-1) for two possible relative
orientations. Frontier molecular orbitals and energies indicated that some
hybridization occurs during the adsorption of HCN on TPy when the molecules have
appropriate relative orientations, resulting in an increase in conductivity.
Considering the changes in the HOMO-LUMO energy gap that were calculated to occur
during HCN adsorption, it is clear that TPy is sensitive to HCN adsorption,
suggesting that TPy has the potential to act as an HCN sensor. Graphical abstract
HCN adsorption on TPy.
PMID- 26419972
TI - Molecular docking and molecular dynamics studies reveal structural basis of
inhibition and selectivity of inhibitors EGCG and OSU-03012 toward glucose
regulated protein-78 (GRP78) overexpressed in glioblastoma.
AB - Glioblastoma (GBM), a malignant form of brain tumor, has a high mortality rate.
GRP78, one of the HSP70 protein family members, is overexpressed in GBM. GRP78 is
the key chaperone protein involved in the unfolded protein response. Upregulated
GRP78 expression in cancer cells inhibits apoptosis and promotes chemoresistance.
GRP78 has an ATPase domain, a substrate-binding domain, and a linker region. ATP
competitive inhibitors such as EGCG and OSU-03012 inhibit GRP78 activity and
reduce its expression in GBM. However, there is a lack of structural data on the
binding modes of these inhibitors to GRP78 ATPase domain. Further, the mode of
selectivity of these inhibitors toward GRP78 also is unknown. Toward this end,
molecular docking was performed with AutoDock Vina and confirmation obtained by
docking using ROSIE. The stability and MM-PBSA binding energy of GRP78-inhibitor
complexes as well as energetic contribution of individual residues was analyzed
by 50 ns molecular dynamics run with GROMACS. MSA by ClustalW2 identified unique
amino acid residues in the ATPase domain of GRP78 which were different from the
residues present in other HSP70 proteins. Important and unique amino acid
residues of GRP78 such as Ile61, Glu293, Arg297, and Arg367 played a major role
in the intermolecular interactions with these inhibitors. The interactions with
unique residues of GRP78 as compared with those of HSP70-1A provided the basis
for selectivity. It was found that the binding affinity and
specificity/selectivity of EGCG toward GRP78 was higher than that toward HSP70
1A, and selectivity was even better than OSU-03012. OSU-03012 was predicted to
bind to GRP78. Analyses from MD runs showed tight binding and stability of
complexes, and the highest number of hydrogen bonds during the trajectory runs
were comparable to those found in the docking studies. Energetic contribution of
individual inhibitor-interacting residues showed that energy values of Ile61 and
Glu293 were among the most negative. These studies are, to the best of our
knowledge, the first studies characterizing EGCG and OSU-03012 interactions with
GRP78 on a structural basis and provide a significant insight into their binding
modes, selectivity, and structural stability.
PMID- 26419974
TI - Accurate Gaussian basis sets for atomic and molecular calculations obtained from
the generator coordinate method with polynomial discretization.
AB - Accurate Gaussian basis sets for atoms from H to Ba were obtained by means of the
generator coordinate Hartree-Fock (GCHF) method based on a polynomial expansion
to discretize the Griffin-Wheeler-Hartree-Fock equations (GWHF). The
discretization of the GWHF equations in this procedure is based on a mesh of
points not equally distributed in contrast with the original GCHF method. The
results of atomic Hartree-Fock energies demonstrate the capability of these
polynomial expansions in designing compact and accurate basis sets to be used in
molecular calculations and the maximum error found when compared to numerical
values is only 0.788 mHartree for indium. Some test calculations with the B3LYP
exchange-correlation functional for N2, F2, CO, NO, HF, and HCN show that total
energies within 1.0 to 2.4 mHartree compared to the cc-pV5Z basis sets are
attained with our contracted bases with a much smaller number of polarization
functions (2p1d and 2d1f for hydrogen and heavier atoms, respectively). Other
molecular calculations performed here are also in very good accordance with
experimental and cc-pV5Z results. The most important point to be mentioned here
is that our generator coordinate basis sets required only a tiny fraction of the
computational time when compared to B3LYP/cc-pV5Z calculations.
PMID- 26419975
TI - Effect of oocyte dysmorphisms on intracytoplasmic sperm injection cycle outcomes
in normal ovarian responders.
AB - AIM: The aim of this study was to identify the influence of oocyte dysmorphisms
on clinical outcomes after intracytoplasmic sperm injection cycle in normal
responders. MATERIAL AND METHODS: In the prospective study, morphology of 1999
metaphase II oocytes retrieved from 316 intracytoplasmic sperm injection cycles
was evaluated from March 2011 to March 2013 at Royan Institute. Controlled
ovarian stimulation was performed by long standard agonist protocol. Oocyte
morphology was assessed before sperm injection by one embryologist. The
associations between fertilization rate, embryo quality and the independent
variables were analyzed using odds ratio (OR) calculated with unconditional
logistic regression test. RESULTS: From all retrieved oocytes, 1543 (77.1%)
showed at least one morphologic aberration. Presence of cytoplasmic vacuoles and
high cytoplasmic viscosity were associated with a significant decrease in the
fertilization rate (OR: 0.5; P = 0.004 and OR: 0.6; P = 0.03, respectively). The
results showed that oocyte morphology did not affect embryo quality. The number
of gonadotrophin injections used showed a direct relation with presence of large
perivitelline space. No significant difference was observed among four groups
(women with total normal morphologic oocytes [group 1], women with total
extracytoplasmic dysmorphic oocytes [group 2], women with total cytoplasmic
dysmorphic oocytes [group 3] and women with total oocytes containing multiple
dysmorphic features [group 4]) in terms of implantation and clinical pregnancy
rates. CONCLUSIONS: Metaphase II oocyte morphology had minor impacts on
fertilization rate, pronuclear morphology and embryo quality in women with normal
ovarian response.
PMID- 26419977
TI - Differential Development of Inflammation and Insulin Resistance in Different
Adipose Tissue Depots Along Aging in Wistar Rats: Effects of Caloric Restriction.
AB - The prevalence of insulin resistance and type 2 diabetes increases with aging and
these disorders are associated with inflammation. Insulin resistance and
inflammation do not develop at the same time in all tissues. Adipose tissue is
one of the tissues where inflammation and insulin resistance are established
earlier during aging. Nevertheless, the existence of different fat depots states
the possibility of differential roles for these depots in the development of age
associated inflammation and insulin resistance. To explore this, we analyzed
insulin signaling and inflammation in epididymal, perirenal, subcutaneous, and
brown adipose tissues during aging in Wistar rats. Although all tissues showed
signs of inflammation and insulin resistance with aging, epididymal fat was the
first to develop signs of inflammation and insulin resistance along aging among
white fat tissues. Subcutaneous adipose tissue presented the lowest degree of
inflammation and insulin resistance that developed latter with age. Brown adipose
tissue also presented latter insulin resistance and inflammation but with lower
signs of macrophage infiltration. Caloric restriction ameliorated insulin
resistance and inflammation in all tissues, being more effective in subcutaneous
and brown adipose tissues. These data demonstrate differential susceptibility of
the different adipose depots to the development of age-associated insulin
resistance and inflammation.
PMID- 26419976
TI - Preparing for an Aging World: Engaging Biogerontologists, Geriatricians, and the
Society.
AB - Although the demographic revolution has produced hundreds of millions people aged
65 and older, a substantial segment of that population is not enjoying the
benefits of extended healthspan. Many live with multiple chronic conditions and
disabilities that erode the quality of life. The consequences are also costly for
society. In the United States, the most costly 5% of Medicare beneficiaries
account for approximately 50% of Medicare's expenditures. This perspective
summarizes a recent workshop on biomedical approaches to best extend healthspan
as way to reduce age-related dysfunction and disability. We further specify the
action items necessary to unite health professionals, scientists, and the society
to partner around the exciting and palpable opportunities to extend healthspan.
PMID- 26419978
TI - Global Multimorbidity Patterns: A Cross-Sectional, Population-Based, Multi
Country Study.
AB - BACKGROUND: Population ageing challenges health care systems due to the high
prevalence and impact of multimorbidity in older adults. However, little is known
about how chronic conditions present in certain multimorbidity patterns, which
could have great impact on public health at several levels. The aim of our study
was to identify and describe multimorbidity patterns in low-, middle-, and high
income countries. METHODS: We analyzed data from the Collaborative Research on
Ageing in Europe project (Finland, Poland, and Spain) and the World Health
Organization's Study on Global Ageing and Adult Health (China, Ghana, India,
Mexico, Russia, and South Africa). These cross-sectional studies obtained data
from 41,909 noninstitutionalized adults older than 50 years. Exploratory factor
analysis was performed to detect multimorbidity patterns. Additional adjusted
binary logistic regressions were performed to identify associations between
sociodemographic factors and multimorbidity. RESULTS: Overall multimorbidity
prevalence was high across countries. Hypertension, cataract, and arthritis were
the most prevalent comorbid conditions. Two or three multimorbidity patterns were
found per country. Several patterns were identified across several countries:
"cardio-respiratory" (angina, asthma, and chronic obstructive pulmonary disease),
"metabolic" (diabetes, obesity, and hypertension), and "mental-articular"
(arthritis and depression). CONCLUSIONS: A high prevalence of multimorbidity
occurs in older adults across countries, with low- and middle-income countries
gradually approaching the figures of richer countries. Certain multimorbidity
patterns are present in several countries, which suggest that common underlying
etiopathogenic factors may play a role. Deeper understanding of these patterns
may lead to the development of preventive actions to diminish their prevalence
and also give rise to new, comprehensive approaches for the management of these
co-occurring conditions.
PMID- 26419980
TI - [Improving the reperfusion therapy for patients with ST-segment elevation
myocardial infarction according to the new guideline].
PMID- 26419981
TI - [Guideline on the diagnosis and therapy of ST-segment elevation myocardial
infarction].
PMID- 26419982
TI - [Chinese expert consensus on clinical application of selective cholesterol
absorption inhibitor (2015)].
PMID- 26419979
TI - Brain Amyloid Deposition Is Associated With Lower Instrumental Activities of
Daily Living Abilities in Older Adults. Results From the MAPT Study.
AB - BACKGROUND: Brain amyloid deposition is one of the key pathological hallmarks
underlying the cognitive changes associated with Alzheimer's disease. Growing
interest has been given to the earliest clinical manifestations of amyloid
plaques. However, the relationship between amyloid status and activities of
everyday function remains largely unknown. In the present study, we examined the
relationship between instrumental activities of daily living performance (using
the ADL-PI score) and amyloid status in older adults. METHODS: Cross-sectional
analyses of data from the Multidomain Alzheimer Preventive Trial (MAPT) were
performed. Volunteers underwent a brain 18F-AV45 positron emission tomography
examination. Bivariate analysis and regression models were conducted to study the
relationships between brain amyloid deposition and the total ADL-PI score.
RESULTS: We included 271 participants (women = 60%; age = 76+/-4 years). Amyloid
positron emission tomography was positive (standard uptake value >=1.17) for 103
participants (38%). The ADL-PI score was lower in amyloid positive participants
than in their amyloid negative counterparts (38.8 vs 40.3, p = .007). This
association was also confirmed in regression models adjusted for age, gender, and
familial history of Alzheimer's disease (odds ratio = 0.94; 95% confidence
interval 0.89-0.99; p = .02). This finding was consistent in cognitively normal
individuals and in those with mild cognitive impairment, using the clinical
dementia rating scale. CONCLUSIONS: This study highlighted an association between
early functional limitations and brain amyloid deposition in elderly subjects.
These symptoms could be the clinical manifestations of amyloid plaques even in
the absence of overt dementia. Further prospective studies are warranted for
examining the evolution of ADL-PI score over the course of Alzheimer's disease.
PMID- 26419983
TI - [Long-term outcomes of patients with unprotected left main coronary artery
disease post revascularization].
AB - OBJECTIVE: To compare the long-term real-world outcomes of consecutive patients
with unprotected left main coronary artery disease (ULMCA) underwent percutaneous
coronary intervention (PCI) with drug-eluting stents (DES) and coronary artery
bypass grafting (CABG). METHODS: Consecutive patients with ULMCA (defined as
stenosis >= 50%) undergoing DES implantation or CABG between January 2003 to July
2009 in Beijing Anzhen Hospital were enrolled. The follow-up period extended
through August 2013. The end points of the study were death, cardiac death,
repeat revascularization, myocardial infarction (MI), stroke, the composite of
cardiac death, MI or stroke and MACCE (major adverse cardiac and cerebrovascular
events, the composite of cardiac death, MI, stroke or repeat revascularization).
RESULTS: From January 2003 to July 2009, 922 ULMCA patients were enrolled in this
study (465 PCI patients, and 457 CABG patients). The median follow-up was 7.1
years (interquartile range 5.3 to 8.2 years). The crude relative risk was as
follows: overall death rate (13.0% (41/465) vs. 22.1% (72/457), P = 0.009),
stroke rate (5.8% (11/465) vs. CABG 18.9% (46/457), P < 0.001) were significantly
lower whereas the rate of repeat revascularization (32.3% (110/465) vs. CABG
19.2% (58/457), P < 0.001) was significantly higher in PCI group than in CABG
group. MI rate was similar between PCI and CABG group (13.9% (33/465) vs. 6.7%
(26/457), P = 0.196). MACCE rate was also similar between the 2 groups (42.9%
(145/465) vs. 42.5% (142/457), P = 0.122). After multivariate adjusting, there
was no significant difference in rates of death, MI and a composite of serious
outcomes (cardiac death, MI, or stroke) between the 2 groups. Rates of MACCE were
significantly higher in the PCI group (P = 0.009) due to increased rate of repeat
revascularization (P < 0.001). However, stroke rate was still significantly
higher in CABG group (P = 0.001) after multivariate adjusting. CONCLUSION: During
a follow-up up to 8.2 years, the survival rate is similar between the PCI and the
CABG group in patients with ULMCA disease. The rate of repeat revascularization
is significantly higher and stroke rate is significantly lower in the PCI group
compared to CABG group.
PMID- 26419984
TI - [Total cholesterol mediates the effect of ABO blood group on coronary heart
disease].
AB - OBJECTIVE: To find a potential link among ABO blood group, lipid profiles and
coronary artery disease (CAD) and to estimate the effect size of connection using
mediation analysis model. METHODS: A total of 898 consecutive patients undergoing
coronary angiography were enrolled, and divided into CAD group and non-CAD group
according to angiographic findings. According to ABO blood group, patients were
divided into O blood group and non-O blood group, as well as A blood group and
non-A blood group. Baseline characteristics among various groups were compared
and the association of ABO blood group, CAD and lipid profile was explored.
RESULTS: Subjects of blood type A had higher concentration of total cholesterol
(TC) and low density lipoprotein cholesterol (LDL-C) compared with that of non-A
type (TC: (4.43 +/- 1.12) mmol/L vs. (4.18 +/- 1.09) mmol/L, LDL-C: (2.79 +/-
0.99) mmo/L vs. (2.59 +/- 1.01) mmol/L, all P < 0.01). TC and LDL-C were
significantly higher while high density lipoprotein cholesterol (HDL-C) and ApoA
I levels were significantly lower in CAD group than in non-CAD group (TC: (4.36
+/- 1.05) mmol/L vs. (4.13 +/- 1.16) mmol/L, LDL-C: (2.61 +/- 0.87) mmol/L vs.
(2.47 +/- 0.94) mmol/L; ApoA I: (1.38 +/- 0.29) mmol/L vs. (1.45 +/- 0.33)
mmol/L; all P < 0.01). After adjustment for traditional cardiovascular risk
factors, blood group A and TC remained significantly associated with the risk of
CAD (OR = 1.88, 95% CI 1.280-2.774, P < 0.01; OR = 1.03, 95% CI 1.018-1.033, P <
0.01, respectively). Specially, mediation analysis indicated that 10.5% of the
effect of A blood group on CAD was mediated by TC levels (P < 0.01). CONCLUSION:
Our data indicate that there is an association between ABO blood group, TC levels
and risk of CAD. Around 10.5% of the effect of A blood group on CAD is mediated
by TC levels.
PMID- 26419985
TI - [Activated clotting time post therapeutic anticoagulation with unfractionated
heparin in patients undergoing elective percutaneous coronary intervention].
AB - OBJECTIVE: To investigate the activated clotting time (ACT) level after
administration of guideline-recommended dose of unfractionated heparin (UFH) and
to confirm the importance of ACT monitoring in percutaneous coronary intervention
(PCI). METHODS: We performed a retrospective study on 1 062 patients undergoing
elective PCI in Peking Union Medical College Hospital from May 1, 2011 to
December 31, 2012. All patients were administrated weight-adjusted UFH (70-100
U/kg) based on PCI guideline of ACCF/AHA/SCAI. Patients were divided into 3
groups: ACT < 300 s (598 cases), ACT 300-350 s (183 cases) and ACT > 350 s (281
cases). ACT level and factors that may affect UFH anticoagulation were analyzed.
RESULTS: (1) The mean age was (63.0 +/- 10.6) years and 751 (70.7%) patients were
men. The mean weight was (70.5 +/- 11.7) kg, and the mean UFH dose used was
(100.7 +/- 9.1) U/kg. (2) The median ACT was 285 (240-352) s after the UFH use.
Pre-defined ACT target (300-350 s) was achieved only in 17.2% (183/1 062)
patients. (3) Age, gender, height, weight, UFH/weight and the risk factors of
coronary heart disease were similar among 3 groups (all P > 0.05). Multifactor
linear correlation analysis showed that UFH/weight was related to ACT level (r =
0.07, P < 0.01), but other factors were not related to ACT level (all P > 0.05).
(4) Among 598 patients with ACT < 300 s, 444 (74.2%) patients received additional
UFH. No major bleeding events were observed in 1 062 patients. The incidence of
minor bleeding and ischemic complications within 48 h after procedure were
similar among 4 groups of ACT < 300 s with additional UFH, ACT < 300 s without
additional UFH, ACT 300-350 s and ACT > 350 s (all P > 0.05). CONCLUSIONS: In
this single-center study, only a small proportion of patients reached the ACT
target after administration of weight-adjusted UFH. Our results supported the
recommendation of ACT monitoring in current PCI guideline to improve efficacy and
safety of UFH anticoagulation therapy.
PMID- 26419986
TI - [Value of fractional flow reserve measurement in intracavitary therapy for
patients with moderate renal artery stenosis].
AB - OBJECTIVE: To analyze the value of fractional flow reserve (FFR) measurement on
endovascular therapy for patients with renal artery stenosis. METHODS: Clinical
data of 9 patients underwent endovascular therapy due to moderate renal artery
stenosis (50%-69%) in Anzhen hospital from May to September 2013 were
retrospectively analyzed. Fractional flow reserve (FFR) were measured in patients
with moderate stenosis in renal artery and abnormal glomerular filtration rate
(GFR) or different between renal artery angiography and ultrasound before the
procedure. Endovascular therapy was not applied for patients with FFR > 0.90, and
the patients were subsequently followed up clinically. Endovascular therapy was
applied in patients with FFR less than 0.90 or the pressure difference between
the two ends of stenosis was more than 20 mmHg (1 mmHg = 0.133 kPa). Blood
pressure, ultrasound and contrast-enhanced ultrasonography data were obtained at
1 and 3 months later, respectively. RESULTS: There were 6 patients diagnosed as
severe renal artery stenosis (>= 70%) and the other 3 patients diagnosed as
moderate renal artery stenosis by renal artery ultrasound before operation. Two
patients with FFR > 0.90 were not undertaken the endovascular therapy. Seven
patients with FFR < 0.90 underwent endovascular therapy. After renal artery
stenting, renal stenosis was relieved immediately and the transstent blood flow
was fluency in these 7 patients. There was significant difference in the FFR
before and after operation (0.81 +/- 0.09 vs.0.94 +/- 0.03, P = 0.008). Among the
patients underwent endovascular therapy, blood pressure was normal without
medication in 2 patients and well controlled with 1 or 2 combined
antihypertensive drugs in the rest 5 patients. CONCLUSION: In patients with
moderate renal artery stenosis, fractional flow reserve measurement could be used
as a useful index to guide intervention procedure and to evaluate the efficacy of
endovascular therapy.
PMID- 26419987
TI - [Association between clinical features and histopathological findings in patients
with left ventricular non-compaction cardiomyopathy].
AB - OBJECTIVE: To investigate the association between clinical and histopathological
features in patients with left ventricular non-compaction cardiomyopathy (LVNC).
METHODS: Histopathological examinations were made on 11 LVNC recipient hearts
from June 2004 to June 2014 in Fuwai Hospital, myocardial ultrastructure changes
were detected using transmission electron microscopy. Association between
clinical and pathological features were analyzed. RESULTS: Patients were (24 +/-
11) years old. There were 6 patients with mucus matrix LVNC, 3 patients with
fibrous fatty infiltration, and 2 patients with cardiomyocytes proliferation. The
gross morphological changes of LVNC hearts were characterized by numerous and
prominent trabeculations with deep intratrabecular recesses in left ventricular
myocardium. Ratios of the thicker noncompacted endocardial layer (N) and thin
epicardial compacted layer (C) (N/C ratio) were >= 2.0, and the most serious
lesions were located in the left ventricular apex, and followed by the left
ventricular free wall. Histological microscopic examinations evidenced numerous
matrix-like material and immature cardiomyocytes on endocardial tissue.
Transmission electron microscopy revealed mitochondrial abnormalities on
morphology, number, and distribution, underdeveloped cardiomyocytes and anomalies
of intercalated disc structure, increased deposition of extracellular matrix-like
substance and perinuclear glycogen. Pathological changes on cytoplasmic matrix
and intercalated disc were present in all three tissue types of LVNC in this
cohort and mitochondria hyperplasia was detected in patients with fibrous fatty
infiltration. Heart weight >= 350 g is often associated with increased number of
mitochondria. Increased cytoplasmic matrix was often detected in patients with
LVEF >= 30% while intercalated disc anomalies were often detected in patients
with LVEF < 30%. CONCLUSION: Histological changes were closely related clinical
features in patients with LVNC.
PMID- 26419988
TI - [Chronic transvenous pacemaker/implantable cardioverter defibrillator leads
implantation induced pathological changes].
AB - OBJECTIVE: Widely pacemaker/implantable cardioverter defibrillator (ICD)
implantation is also related to an increasing need for transvenous lead
extraction. Understanding the location and extent of pathological changes,
including adhesions and fibrous tissue formation along the course of chronic
pacemaker/ICD leads, are essential for operators performing lead extraction
operations in order to reduce the potential life threatening complications.
METHODS: Three parts are included in the research, pathological examination on 83
extracted pacemaker/ICD leads using excimer laser technique from March 2008 to
March 2011, autopsy examination of one died patient during lead extraction for
lead-related infective endocarditis, and anatomical analysis on pacemaker/ICD
leads from 10 patients died of other non-cardiac causes. RESULTS: Extensive
encapsulated fibrous tissue around the leads and extensive adhesion/fibrosis
along the course of the leads from venous entry site to the lead/myocardial
interface could be detected on transvenous pacemaker/ICD leads. Since the tissue
at the junction between superior vena cava (SVC) and right atrium (RA) is very
thin, free of pericardium, thus, this is a common place for extensive
adhesion/fibrosis and myocardial perforation/tear during lead extraction, which
accounted for one death during extraction in our cohort. Extensive adhesion and
fibrosis were also observed at the tricuspid valve and subvalvular structures.
Leads implanted to the right ventricular apex were close to the epicardial
surface and prone to perforation through myocardium. It is common to observe
thrombus on the leads or at the interface between leads and myocardial tissue,
especially at right atrial appendage (RAA) at the site of lead insertion.
CONCLUSION: Extensive adhesions and fibrosis can be commonly seen along the
course of pacemaker/ICD leads, and at SVC to RA junction, the tricuspid
valve/subvalvular structures, and RA/RV lead interface. The tissue at SVC to RA
junction is very thin, making it vulnerable for myocardial perforation/tear
during lead extraction. Thrombus is commonly seen along the leads or at the lead
tissue interface.
PMID- 26419989
TI - [Value of patient health questionnaires (PHQ)-9 and PHQ-2 for screening
depression disorders in cardiovascular outpatients].
AB - OBJECTIVE: To analyze the value of 2- and 9-question patient health
questionnaires (PHQ-2 and PHQ-9) for screening status of depression in
cardiovascular outpatients. METHODS: From June 2013 to January 2014, a total of
201 outpatients from psycho-cardiological outpatients departments were
consecutively enrolled into this study. All patients were asked to complete PHQ-9
and the mental psychological assessment by qualified researchers trained by
psychiatry according to the composite international diagnostic interviews (CIDI),
50 cases were retested to assess the retest reliability after one week. The PHQ-2
and PHQ-9 were validated with the CIDI as the reference criteria. RESULTS:
According to the CIDI, 42 (21.3%) out of the 201 outpatients were diagnosed as
depression. For PHQ-9 scale, a cutoff value of 10 presented satisfactory results
with 87.1% sensitivity, 83.5% specificity, 58.7% positive predicting value, 95.6%
negative predicting value and the area under the ROC curve (AUC) was 0.877 (SE =
0.032, 95% CI: 0.813-0.938). The Cronbach's alpha coefficients and test-retest
reliability of the PHQ-9 were 0.809 and 0.882, respectively. Compared with CIDI,
the cutoff value of the PHQ-2 was 3 with 85.7% sensitivity, 69.2% specificity,
57.1% positive predicting value, 93.6% negative predicting value, and the AUC was
0.806 (SE = 0.042, 95% CI: 0.774-0.889). The Cronbach's alpha coefficients and
test-retest reliability of the PHQ-2 were 0.785 and 0.813, respectively.
CONCLUSION: The PHQ-2 and PHQ-9 are reliable and efficient instruments for
screening and especially excluding depression in cardiovascular outpatients.
PMID- 26419990
TI - [Ad-hVEGF165 reverses homocysteine-induced endothelial dysfunction by regulating
nitric oxide system].
AB - OBJECTIVE: To investigate the therapeutic effect of Ad-hVEGF165 on the
endothelial cells dysfunction induced by homocysteine (Hcy) and related molecular
mechanisms. METHODS: Human umbilical vein endothelial cells CRL-1730 were treated
with Hcy at different concentrations (0, 0.05, 1.00 mmol/L) for 24 h. The same
concentration of Hcy, Ad-Track and Ad-hVEGF165 were added to the cells in the
following groups: blank group, Hcy0.05 group, Hcy1.00 group, Ad-Track group,
Hcy0.05+Ad-Track group, Hcy1.00+Ad-Track group, Ad-hVEGF165 group, Hcy0.05+Ad
hVEGF165 group, Hcy1.00+ Ad-hVEGF165 group for 48 h. The mRNA and protein
expressions of eNOS and DDAH2 were detected by real-time PCR and Western blot.
The correlations of mRNA and protein expressions between endothelial nitric oxide
synthase (eNOS) and dimethylarginine dimthylaminohydrolase (DDAH)2 were evaluated
by Pearson correlation analysis. RESULTS: Compared with blank group and Ad
hVEGF165 group, the mRNA and protein expressions of eNOS were decreased in
Hcy0.05 group and Hcy0.05+Ad-hVEGF165 group (both P < 0.05), and the mRNA and
protein expressions of DDAH2 in cells treated with 0.05 mmol/L and 1.00 mmol/L
Hcy were reduced as well (all P < 0.05). DDAH2 mRNA and protein expression are
increased (all P < 0.05) in Ad-hVEGF165 group compared with the blank group and
Ad-Track, Hcy0.05 + Ad-hVEGF165 and Hcy0.05 group compared with Hcy0.05+Ad-Track
group, Hcy1.00+Ad-hVEGF165 and Hcy1.00 group compared with Hcy1.00+Ad-Track
group. The mRNA and protein expressions of eNOS and DDAH2 were uncorrelated under
the effect of Hcy (r = 0.057 and 0.449, both P > 0.05) and VEGF (r = 0.284 and
0.432, both P > 0.05). CONCLUSION: Recombinant adenovirus Ad-hVEGF165 could
reverse Hcy-induced endothelial cells dysfunction via upregulating the
expressions of eNOS and DDAH2.
PMID- 26419991
TI - [Experimental studies on the role of GATA4 in the endocardial cushions
development].
AB - OBJECTIVE: To investigate the role of GATA4 gene in the endocardial cushions
development. METHODS: Target gene eukaryote expression vectors were constructed
by pcDNA3.1(-) vector plasmid, and were identified by DNA sequence analysis.
Recombinant plasmids were transfected into Hela cells with lipofectamine 2000,
meanwhile Hela cells transfected with empty vector or those without transfection
served as transfection control group and blank control group, respectively. Real
time PCR and Western blot were performed to detect the relative expression of
mRNA and protein of transcription factors GATA4, Sox9, Scleraxis and ECM proteins
Aggrecan, Tenascin in each group. RESULTS: The relative mRNA expression of GATA4
in experimental group was significantly higher than in transfection control group
and blank control group. GATA4 mRNA expression in Hela(GATA4), Hela(H436Y),
Hela(Null) and Hela group was 310.83 +/- 2.39, 146.35 +/- 1.74, 0.94 +/- 0.32,
1.00 +/- 0.28, respectively (F = 72.508, P < 0.05). Western blot results were
consistent with the results obtained by qRT-PCR. The relative mRNA and protein
expressions of Sox9, Scleraxis, Aggrecan and Tenascin in both experimental groups
were significantly higher than that in transfection control group and blank
control group (P < 0.05), and above gene expressions were significantly
downregulated in GATA4(H436Y) group, while they were similar between transfection
control group and blank control group (all P > 0.05). CONCLUSIONS: GATA4 H436Y
mutation reduces it's transcriptional activation, which might serve as a
theoretical framework to demonstrate the roles of GATA4 gene in endocardial
cushion development.
PMID- 26419992
TI - [STAT signaling pathway mediates high glucose induced cardiac fibroblasts
proliferation and collagen deposition in vitro].
AB - OBJECTIVE: To observe the signal transducers and activator of transcriptions
(STATs) protein expression changes and investigate the functional role of STATs
pathway in case of high glucose-induced cardiac fibroblasts (CFs) proliferation
and collagen deposition in vitro. METHODS: Rat cardiac fibroblasts were isolated
from 1- to 3-day-old SD rats, cells from the second to fourth passages were used
for the experiment. CFs were cultured in Dulbecco's modified Eagle's medium,
supplemented with 5.5 mmol/L glucose (NG), 5.5 mmol/L glucose plus 19.4 mmol/L
mannose (OC) or 25 mmol/L glucose (HG) in the presence of absence of STAT1
inhibitor (fludarabine, FLU) and STAT3 inhibitor (S3I-201). After 24 h and 48 h
culture in vitro, the proliferation of CFs was measured by 3-(4,5-dimethyl-2
thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After 12 h and 24 h
culture in vitro, the production of type I and III collagen was evaluated using
real-time quantitative PCR and ELISA. After 0, 30, 60 and 120 min culture in
vitro, the phosphorylated expression of STAT1 and STAT3 was analyzed by Western
blot. RESULTS: CFs proliferation was significantly enhanced post 24 h and 48 h HG
stimulation, and procollagen I and III mRNA expression was significantly
upregulated post 12 h and 24 h HG stimulation. Deposition of collagen I and III
was also significantly increased post 24 h and 72 h HG stimulation. STAT1
phosphorylation in CFs was increased after 120 min HG stimulation and STAT3
phosphorylation in CFs was increased post 60 min and 120 min HG stimulation. FLU
and S3I-201 could inhibit HG-induced CFs proliferation and suppress of which was
stimulated by FLU and S3I-201 could both suppress upregulated procollagen I and
III mRNA expression and the deposition of collagen types I and III post HG
stimulation. STAT1 phosphorylation inhibition resulted in less mRNA
downregulation of procollagen type III than that of procollagen type I post 12 h
HG stimulation. The STAT3 phosphorylation inhibition resulted in more
significantly upregulated procollagen type III mRNA expression than procollagen
type I mRNA expression at 12 h post HG stimulation. CONCLUSION: HG could enhance
the protein expression of phosphorylated STAT1 and STAT3 in CFs, which are
responsible for HG-induced increased CFs proliferation and collagen deposition in
vitro.
PMID- 26419993
TI - [Comparison of heart rate variability measurements between ballistocardiogram and
electrocardiography].
AB - OBJECTIVE: To compare the heart rate variability (HRV) measurements between
ballistocardiogram (BCG) and electrocardiography (ECG). METHODS: The signals of
BCG and ECG of 21 patients were collected synchronously. JJ intervals of BCG and
RR intervals of ECG were used to calculate the cardiac periods. The parameters of
HRV analysis were calculated in time domain analysis, frequency domain analysis
and nonlinear analysis. The results derived from BCG and ECG were compared.
RESULTS: The parameters of HRV analysis calculated from BCG and ECG had high
similarity. The correlation coefficients of SDNN, TP, LF, HF and SD2 between the
BCG and ECG methods were high (r = 1). The correlation coefficients of rMSSD and
SD2 were 0.99 and of PNN50 and LF/HF were 0.98 between the two methods. HRV
analysis results derived from the two methods were similar (P > 0.05).
CONCLUSION: HRV could also be measured reliably by calculating the JJ interval
from BCG.
PMID- 26419994
TI - [Levosimendan-induced liver damage in an elderly patient with heart failure].
PMID- 26419995
TI - [Anomalous origin of left main coronary artery from the pulmonary artery: a case
report].
PMID- 26419996
TI - [Update on the new oral anticoagulants and prevention of coronary artery
disease].
PMID- 26419997
TI - [Association between scientific view of health and bioethics].
PMID- 26419998
TI - [Research progress on association between red blood cell distribution width and
cardiovascular disease].
PMID- 26420000
TI - Specific Accumulation of Lanthanum Carbonate in the Gastric Mucosal Histiocytes
in a Dialysis Patient.
PMID- 26419999
TI - Which heart failure patients profit from natriuretic peptide guided therapy? A
meta-analysis from individual patient data of randomized trials.
AB - AIMS: Previous analyses suggest that heart failure (HF) therapy guided by (N
terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left
ventricular ejection fraction, age and co-morbidities, but the reasons remain
unclear. METHODS AND RESULTS: To determine interactions between (NT-pro)BNP
guided therapy and HF with reduced [ejection fraction (EF) <=45%; HF with reduced
EF (HFrEF), n = 1731] vs. preserved EF [EF > 45%; HF with preserved EF (HFpEF), n
= 301] and co-morbidities (hypertension, renal failure, chronic obstructive
pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease)
on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance
trials were analysed using Cox-regression with multiplicative interaction terms.
Endpoints were mortality and admission because of HF. Whereas in HFrEF patients
(NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower
mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62-0.97, P =
0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67-0.97, P = 0.02), no such
effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76-1.96, P = 0.41; HF
admissions HR = 1.01, 95% CI 0.67-1.53, P = 0.97; interactions P < 0.02). Age (74
+/- 11 years) interacted with treatment strategy allocation independently of EF
regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction
of age and mortality was explained by the interaction of treatment strategy
allocation with co-morbidities. In HFpEF, renal failure provided strongest
interaction (P < 0.01; increased risk of (NT-pro)BNP-guided therapy if renal
failure present), whereas in HFrEF patients, the presence of at least two of the
following co-morbidities provided strongest interaction (P < 0.01; (NT-pro)BNP
guided therapy beneficial only if none or one of chronic obstructive pulmonary
disease, diabetes, cardiovascular insult, or peripheral vascular disease
present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without
hypertension (P = 0.02). CONCLUSION: The benefits of therapy guided by (NT
pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response
to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach
in elderly patients.
PMID- 26420001
TI - EEG Topographic Mapping of Visual and Kinesthetic Imagery in Swimmers.
AB - This study investigated differences in QEEG measures between kinesthetic and
visual imagery of a 100-m swim in 36 elite competitive swimmers. Background
information and post-trial checks controlled for the modality of imagery,
swimming skill level, preferred imagery style, intensity of image and task
equality. Measures of EEG relative magnitude in theta, low (7-9 Hz) and high
alpha (8-10 Hz), and low and high beta were taken from 19 scalp sites during
baseline, visual, and kinesthetic imagery. QEEG magnitudes in the low alpha band
during the visual and kinesthetic conditions were attenuated from baseline in low
band alpha but no changes were seen in any other bands. Swimmers produced more
low alpha EEG magnitude during visual versus kinesthetic imagery. This was
interpreted as the swimmers having a greater efficiency at producing visual
imagery. Participants who reported a strong intensity versus a weaker feeling of
the image (kinesthetic) had less low alpha magnitude, i.e., there was use of more
cortical resources, but not for the visual condition. These data suggest that low
band (7-9 Hz) alpha distinguishes imagery modalities from baseline, visual
imagery requires less cortical resources than kinesthetic imagery, and that
intense feelings of swimming requires more brain activity than less intense
feelings.
PMID- 26420003
TI - Scientific theory, the publishing crisis and the wisdom of editors.
PMID- 26420002
TI - Endocannabinoids and related lipids in blood plasma following touch massage: a
randomised, crossover study.
AB - BACKGROUND: The endocannabinoid system is involved in the regulation of stress
and anxiety. In a recent study, it was reported that short-term changes in mood
produced by a pleasant ambience were correlated with changes in the levels of
plasma endocannabinoids and related N-acylethanolamines (Schrieks et al. PLoS One
10: e0126421, 2015). In the present study, we investigated whether stress
reduction by touch massage (TM) affects blood plasma levels of endocannabinoids
and related N-acylethanolamines. RESULTS: A randomized two-session crossover
design for 20 healthy participants was utilised, with one condition that
consisted of TM and a rest condition as control. TM increased the perceived
pleasantness rating of the participants, and both TM and rest reduced the basal
anxiety level as assessed by the State scale of the STAI-Y inventory. However,
there were no significant effects of either time (pre- vs. post-treatment
measures) as main effect or the interaction time x treatment for the plasma
levels of the endocannabinoids anandamide and 2-arachidonoylglycerol or for eight
other related lipids. Four lipids showed acceptable relative reliabilities, and
for two of these (linoleoyl ethanolamide and palmitoleoyl ethanolamide) a
significant correlation was seen between the TM-related change in levels,
calculated as (post-TM value minus pre-TM value) - (post-rest value minus pre
rest value), and the corresponding TM-related change in perceived pleasantness.
CONCLUSIONS: It is concluded that in the participants studied here, there are no
overt effects of TM upon plasma endocannabinoid levels. Possible associations of
related N-acylethanolamines with the perceived pleasantness should be
investigated further.
PMID- 26420012
TI - A numerical framework to investigate hemodynamics during endovascular mechanical
recanalization in acute stroke.
AB - Ischemic stroke, caused by embolism of cerebral vessels, inflicts high morbidity
and mortality. Endovascular aspiration of the blood clot is an interventional
technique for the recanalization of the occluded arteries. However, the
hemodynamics in the Circle of Willis (CoW) are not completely understood, which
results in medical misjudgment and complications during surgeries. In this study
we establish a multiscale description of cerebral hemodynamics during aspiration
thrombectomy. First, the CoW is modeled as a 1D pipe network on the basis of
computed tomography angiography (CTA) scans. Afterwards, a vascular occlusion is
placed in the middle cerebral artery and the relevant section of the CoW is
transferred to a 3D computational fluid dynamic (CFD) domain. A suction catheter
in different positions is included in the CFD simulations. The boundary
conditions of the 3D domain are taken from the 1D domain to ensure system
coupling. A Eulerian-Eulerian multiphase simulation describes the process of
thrombus aspiration. The physiological blood flow in the 1D and 3D domains is
validated with literature data. Further on, it is proved that domain reduction
and pressure coupling at the boundaries are an appropriate method to reduce
computational costs. Future work will apply the developed framework to various
clinical questions.
PMID- 26420011
TI - Persistent organic pollutants and non-alcoholic fatty liver disease in morbidly
obese patients: a cohort study.
AB - BACKGROUND: In animal experiments persistent organic pollutants (POPs) cause
hepatosteatosis. In epidemiological studies POPs have positive associations with
serum markers of nonalcoholic fatty liver disease (NAFLD) and together with
obesity synergistic association with insulin resistance. Because insulin
resistance and obesity are critical in NAFLD pathogenesis, we investigated the
association of serum pollutant levels with liver histology and alanine
aminotransferase (ALT) in morbidly obese. METHODS: Liver biopsies were from 161
participants of the Kuopio Obesity Surgery Study (KOBS) who underwent bariatric
surgery 2005-2011. Liver histology was categorized as normal, steatosis and non
alcoholic steatohepatitis (NASH). Liver phenotype at baseline and ALT at baseline
and 12 months post-surgery were correlated to serum POP concentrations at
respective time points. As lipophilic POPs concentrate to smaller fat volume
during weight loss, serum levels before and 12 months after bariatric surgery
were compared. RESULTS: Baseline serum concentration of PCB-118, beta-HCH and
several PFAAs had an inverse association with lobular inflammation possibly due
to changes in bile acid metabolism. ALT had negative associations with many POPs
at baseline that turned positive at 12 months after major clinical improvements.
There was an interaction between some POPs and sex at 12 months, and in
stratified data positive associations were observed mainly in females but not in
males. CONCLUSIONS: We found a negative association between serum concentrations
of PCB-118, beta-HCH and several PFAAs with lobular inflammation at baseline.
Positive POPs-ATL associations at 12 months among women suggest that increased
POP concentrations may decrease the degree of liver recovery.
PMID- 26420013
TI - Molecular-matched materials for anticancer drug delivery and imaging.
AB - AIM: In this study, we aim to construct nanoformulation with high-cargo loading
and controlled serum kinetics. MATERIALS & METHODS: Molecular-matched materials
(MMMs) are established through the conjugation of the functional moiety to a
molecule representative of the nanoparticle's core. Molecular-matched
nanoemulsions and liposomes were prepared using MMMs. RESULTS: This technique
based on MMMs even allows us to efficiently load either hydrophobic or
hydrophilic moieties into a hydrophobic core of the nanoparticles. MMMs-based
nanoparticles showed marked improvement in serum pharmacokinetics and anticancer
effect. CONCLUSION: The desired performance can be achieved when the hydrophobic
anchor of the PEG derivatives and the moiety conjugated to the therapeutic (or
imaging) agents are molecularly identical to the core.
PMID- 26420014
TI - Paternalism and autonomy: views of patients and providers in a transitional (post
communist) country.
AB - BACKGROUND: Patient autonomy is a fundamental, yet challenging, principle of
professional medical ethics. The idea that individual patients should have the
freedom to make choices about their lives, including medical matters, has become
increasingly prominent in current literature. However, this has not always been
the case, especially in communist countries where paternalistic attitudes have
been interwoven into all relationships including medical ones. Patients'
expectations and the role of the doctor in the patient-physician relationship are
changing. Croatia, as a transitional country, is currently undergoing this
particular process. METHODS: Qualitative research was conducted by means of six
focus group discussions held in the years 2012 and 2013 in Croatia. Focus groups
were held separately with each of the following: first year and final (6(th))
year medical students, physicians engaged in medical ethics education, physicians
practicing in a clinical hospital, family medicine residents and individuals
representing patients with chronic disease. This research specifically addresses
issues related to patient autonomy, in particular, the principles of truth
telling, confidentiality, and informed consent. All focus group discussions were
audio taped and then transcribed verbatim and systematized according to
acknowledged qualitative analysis methods. RESULTS AND DISCUSSION: Patient
autonomy is much more than a simple notion defined as the patient's right to make
treatment decisions independently. It has to be understood in context of the
broader socio-cultural setting. At present, both patients and medical doctors in
Croatia are increasingly appreciating the importance of promoting the principle
of autonomy in medical decision-making. However, the current views of medical
students, physicians and patients reveal inconsistencies. CONCLUSIONS: Knowing
how to respect the various facets of patients' autonomy should be part of
physician's professional duties, and also be reflected in his or her core
clinical competencies. For this reason greater importance should be dedicated to
patient autonomy issues in medical education in Croatia.
PMID- 26420015
TI - Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a
high fructose diet.
AB - BACKGROUND: Metabolic syndrome is a growing worldwide health problem. We
evaluated the effects of wine grape powder (WGP), rich in antioxidants and fiber,
in a rat model of metabolic syndrome induced by a high fructose diet. We tested
whether WGP supplementation may prevent glucose intolerance and decrease
oxidative stress in rats fed with a high fructose diet. METHODS: Male Sprague
Dawley rats weighing 180 g were divided into four groups according to their
feeding protocols. Rats were fed with control diet (C), control plus 20 % WGP (C
+ WGP), 50 % high fructose (HF) or 50 % fructose plus 20 % WGP (HF + WGP) for 16
weeks. Blood glucose, insulin and triglycerides, weight, and arterial blood
pressure were measured. Homeostasis model assessment (HOMA) index was calculated
using insulin and glucose values. A glucose tolerance test was performed 2 days
before the end of the experiment. As an index of oxidative stress, thiobarbituric
acid reactive substances (TBARS) level was measured in plasma and kidney, and
superoxide dismutase was measured in the kidney. RESULTS: Thiobarbituric acid
reactive substances in plasma and renal tissue were significantly higher when
compared to the control group. In addition, the area under the curve of the
glucose tolerance test was higher in HF fed animals. Furthermore, fasting blood
glucose, plasma insulin levels, and the HOMA index, were also increased. WGP
supplementation prevented these alterations in rats fed with the HF diet. We did
not find any significant difference in body weight or systolic blood pressure in
any of the groups. CONCLUSIONS: Our results show that WGP supplementation
prevented hyperglycemia, insulin resistance and reduced oxidative stress in rats
fed with HF diet. We propose that WGP may be used as a supplement in human food
as well.
PMID- 26420016
TI - Evidence for abnormal cytokine expression in Gulf War Illness: A preliminary
analysis of daily immune monitoring data.
AB - BACKGROUND: Gulf War Illness (GWI) is a clinically heterogeneous chronic
condition that affects many veterans of the 1990-1991 Persian Gulf War. One of
the most prevalent and debilitating symptoms of GWI is abnormal fatigue. The
mechanisms underlying GWI generally, and fatigue symptoms specifically, have yet
to be conclusively identified, although immune system abnormalities are suspected
to be involved. The first goal of this immune monitoring study was to determine
if GWI is associated with higher absolute levels and daily variability of pro
inflammatory immune factors. The second goal was to explore the relationship
between day-to-day immune marker fluctuations and daily self-reported fatigue
severity. METHODS: We recruited veterans with GWI and healthy veteran control
(HV) participants to provide self-reported fatigue severity data and blood
samples, over 25 consecutive days. We profiled inflammatory processes by using a
longitudinal, daily immune-monitoring approach. For each day, serum cytokine and
chemokine concentrations were determined using multiplex assays. RESULTS: Seven
veterans with GWI and eight healthy veteran control (HV) participants completed
the study protocol. We found that GWI was associated with higher variability in
the expression of eotaxin-1 (p < 0.001). For GWI participants, higher fatigue
severity days were associated with greater IL-1beta (p = 0.008) and IL-15 (p <
0.001). CONCLUSIONS: Our findings provide preliminary evidence that the immune
system is involved in the pathophysiology of GWI. Longitudinal immune profiling
approaches may be helpful in discovering targets for novel therapies in
conditions such as GWI.
PMID- 26420018
TI - Negotiating the dilemma of anaesthesia and sedation in NICUs.
PMID- 26420019
TI - Arginine analogues incorporating carboxylate bioisosteric functions are
micromolar inhibitors of human recombinant DDAH-1.
AB - Dimethylarginine dimethylaminohydrolase (DDAH) is a key enzyme involved in the
metabolism of asymmetric dimethylarginine (ADMA) and N-monomethyl arginine
(NMMA), which are endogenous inhibitors of the nitric oxide synthase (NOS) family
of enzymes. Two isoforms of DDAH have been identified in humans, DDAH-1 and DDAH
2. DDAH-1 inhibition represents a promising strategy to limit the overproduction
of NO in pathological states without affecting the homeostatic role of this
important messenger molecule. Here we describe the design and synthesis of 12
novel DDAH-1 inhibitors and report their derived kinetic parameters, IC50 and Ki.
Arginine analogue 10a, characterized by an acylsulfonamide isosteric replacement
of the carboxylate, showed a 13-fold greater inhibitory potential relative to the
known DDAH-1 inhibitor, L-257. Compound 10a was utilized to study the putative
binding interactions of human DDAH-1 inhibition using molecular dynamics
simulations. The latter suggests that several stabilizing interactions occur in
the DDAH-1 active-site, providing structural insights for the enhanced inhibitory
potential demonstrated by in vitro inhibition studies.
PMID- 26420020
TI - A brief history of pediatric urologic oncology as a subspecialty.
PMID- 26420021
TI - Proteomic analysis reveals differentially secreted proteins in the urine from
patients with clear cell renal cell carcinoma.
AB - OBJECTIVE: The aim of this study was to evaluate the differentially secreted
protein profile in the urine from patients with clear cell renal cell carcinoma
(ccRCC) using mass spectrometry-based methods. Urine composition can reflect
kidney physiology and can be used to detect markers for renal diseases. Moreover,
characterization of the secretome is likely to assist in the investigation of new
drugs for biological targets and diagnose the ccRCC at an early stage. METHODS
AND MATERIALS: Urine samples from patients were divided according to Fuhrman
degree (FI-IV), which was associated with the cellular differentiation as good
prognosis (GP) and poor prognosis (PP). Healthy individuals were used as the
control group (CG). We used both qualitative and quantitative mass spectrometry
based analyses that involved the following approaches: 1-dimensional gel
electrophoresis combined with liquid chromatography mass spectrometry in tandem
(1DE LC-MS/MS), in-solution digestion combined with label-free 1-dimensional LC
MS(E) (1D LC-MS(E)), and bidimensional gel electrophoresis combined with matrix
assisted laser desorption/ionization time of flight in tandem (2DE MALDI-TOF/TOF)
or combined with LC-MS/MS. RESULTS: All the strategies allowed the identification
of 354 proteins from the CG, GP, and PP groups. Qualitative experiments using 1DE
LC-MS/MS analysis detected different protein profiles, and 224 proteins were
identified in all groups. The label-free MS(E) quantitative analysis identified
113 proteins and generated novel information on secreted protein profiles,
including 49 up-secreted proteins in the urine from patients with ccRCC and 40
down-secreted proteins related to the CG. Proteins such as kininogen-1,
uromodulin, apolipoprotein D, polyubiquitin, and CD59 glycoprotein were down
secreted according to the groups CG>GP>PP. In contrast, apolipoprotein A,
fibrinogen, and haptoglobin were up secreted in patient groups. The same
expression profile observed for kininogen-1, apolipoprotein D, fibrinogen, and
haptoglobin was corroborated by 2DE LC-MS/MS or 2DE MALDI-TOF/TOF analyses. These
2 strategies also showed 13 differentially secreted proteins among the 3 groups.
CONCLUSIONS: The proteins kininogen-1, apolipoprotein D, fibrinogen, and
haptoglobin presented similar quantitative protein profiles according to MS(E)
and 2DE approaches. The latter proteins were up secreted and the former ones were
down-regulated. The strategies used proved to be valuable in identifying proteins
that were differentially secreted in urine from patients with RCC.
PMID- 26420022
TI - There is a place for radical cystectomy and urinary diversion, including
orthotopic bladder substitution, in patients aged 75 and older: Results of a
retrospective observational analysis from a high-volume center.
AB - INTRODUCTION: The incidence of cancer increases with age and owing to the
changing demographics we are increasingly confronted with treating bladder cancer
in old patients. We report our results in patients>75 years of age who underwent
open radical cystectomy (RC) and urinary diversion. MATERIAL AND METHODS: From
January 2000 to March 2013, a consecutive series of 224 old patients with
complete follow-up who underwent RC and urinary diversion (ileal orthotopic
bladder substitute [OBS], ileal conduit [IC], and ureterocutaneostomy [UCST])
were included in this retrospective single-center study. End points were the 90
day complication rates (Clavien-Dindo classification), 90-day mortality rates,
overall and cancer-specific survival rates, and continence rates (OBS). RESULTS:
Median age was 79.2 years (range: 75.1-91.6); 35 of the 224 patients (17%)
received an OBS, 178 of the 224 patients (78%) an IC, and 11 of the 224 patients
(5%) an UCST. The 90-day complication rate was 54.3% in the OBS (major: Clavien
grade 3-5: 22.9%, minor: Clavien Grade 1-2: 31.4%), 56.7% in the IC (major: 27%,
minor: 29.8%), and 63.6% in the UCST group (major: 36.4%, minor: 27.3%); P =
0.001. The 90-day mortality was 0% in the OBS group, 13% in the IC group, and 10%
in the UCST group (P = 0.077). The Glasgow prognostic score was an independent
predictor of all survival parameters assessed, including 90-day mortality. Median
follow-up was 22 months. Overall and cancer-specific survivals were 90 and 98, 47
and 91, and 11 and 12 months for OBS, IC, and UCST, respectively. In OBS
patients, daytime continence was considered as dry in 66% and humid in 20% of
patients. Nighttime continence was dry in 46% and humid 26% of patients.
CONCLUSION: With careful patient selection, oncological and functional outcome
after RC can be good in old patients. Old age as the sole criterion should not
preclude the indication for RC or the option of OBS. In old patients undergoing
OBS, satisfactory continence results can be achieved.
PMID- 26420023
TI - Efficient singlet oxygen generation from sugar pendant C60 derivatives for
photodynamic therapy.
AB - The amidation reaction between C60 with an activated ester group (1) and
acetylated Glc (AcGlc) with an amino group (2) was performed to yield the target
AcGlc-pendant C60 compound (3). The water soluble deacetylated compound, Glc
pendant C60 compound (4), exhibited high photocytotoxicity against HeLa cells due
to the more efficient singlet oxygen generation as compared with that of Glc
pendant azafulleroids.
PMID- 26420024
TI - Ammonia activates pacC and patulin accumulation in an acidic environment during
apple colonization by Penicillium expansum.
AB - Penicillium expansum, the causal agent of blue mould rot, causes severe post
harvest fruit maceration simultaneously with the secretion of d-gluconic acid
(GLA) and the mycotoxin patulin in colonized tissue. The factor(s) inducing
patulin biosynthesis during colonization of the host acidic environment is
unclear. During the colonization of apple fruit in vivo and growth in culture, P.
expansum secretes pH-modulating GLA and ammonia. Although patulin and its
possible opportunistic precursor GLA accumulate together during fungal
development, ammonia is detected on the colonized tissue's leading edge and after
extended culture, close to patulin accumulation. Here, we demonstrate ammonia
induced transcript activation of the global pH modulator PacC and patulin
accumulation in the presence of GLA by: (i) direct exogenous treatment of P.
expansum growing on solid medium; (ii) direct exogenous treatment on colonized
apple tissue; (iii) growth under self-ammonia production conditions with limited
carbon; and (iv) analysis of the transcriptional response to ammonia of the
patulin biosynthesis cluster. Ammonia induced patulin accumulation concurrently
with the transcript activation of pacC and patulin biosynthesis cluster genes,
indicating the regulatory effect of ammonia on pacC transcript expression under
acidic conditions. Electrophoretic mobility shift assays using P. expansum PacC
and antibodies to the different cleaved proteins showed that PacC is not
protected against proteolytic signalling at pH 4.5 relative to pH 7.0, but NH4
addition did not further enhance its proteolytic cleavage. Ammonia enhanced the
activation of palF transcript in the Pal pathway under acidic conditions. Ammonia
accumulation in the host environment by the pathogen under acidic pH may be a
regulatory cue for pacC activation, towards the accumulation of secondary
metabolites, such as patulin.
PMID- 26420017
TI - Sedation and analgesia practices in neonatal intensive care units (EUROPAIN):
results from a prospective cohort study.
AB - BACKGROUND: Neonates who are in pain or are stressed during care in the intensive
care unit (ICU) are often given sedation or analgesia. We investigated the
current use of sedation or analgesia in neonatal ICUs (NICUs) in European
countries. METHODS: EUROPAIN (EUROpean Pain Audit In Neonates) was a prospective
cohort study of the management of sedation and analgesia in patients in NICUs.
All neonates admitted to NICUs during 1 month were included in this study. Data
on demographics, methods of respiration, use of continuous or intermittent
sedation, analgesia, or neuromuscular blockers, pain assessments, and drug
withdrawal syndromes were gathered during the first 28 days of admission to
NICUs. Multivariable linear regression models and propensity scores were used to
assess the association between duration of tracheal ventilation (TV) and exposure
to opioids, sedatives-hypnotics, or general anaesthetics in neonates (O-SH-GA).
This study is registered with ClinicalTrials.gov, number NCT01694745. FINDINGS:
From Oct 1, 2012, to June 30, 2013, 6680 neonates were enrolled in 243 NICUs in
18 European countries. Mean gestational age of these neonates was 35.0 weeks (SD
4.6) and birthweight was 2384 g (1007). 2142 (32%) neonates were given TV, 1496
(22%) non-invasive ventilation (NIV), and 3042 (46%) were kept on spontaneous
ventilation (SV). 1746 (82%), 266 (18%), and 282 (9%) neonates in the TV, NIV,
and SV groups, respectively, were given sedation or analgesia as a continuous
infusion, intermittent doses, or both (p<0.0001). In the participating NICUs, the
median use of sedation or analgesia was 89.3% (70.0-100) for neonates in the TV
group. Opioids were given to 1764 (26%) of 6680 neonates and to 1589 (74%) of
2142 neonates in the TV group. Midazolam was given to 576 (9%) of 6680 neonates
and 536 (25%) neonates of 2142 neonates in the TV group. 542 (25%) neonates in
the TV group were given neuromuscular blockers, which were administered as
continuous infusions to 146 (7%) of these neonates. Pain assessments were
recorded in 1250 (58%) of 2138, 672 (45%) of 1493, and 916 (30%) of 3017 neonates
in the TV, NIV, and SV groups, respectively (p<0.0001). In the univariate
analysis, neonates given O-SH-GA in the TV group needed a longer duration of TV
than did those who were not given O-SH-GA (mean 136.2 h [SD 173.1] vs 39.8 h
[94.7] h; p<0.0001). Multivariable and propensity score analyses confirmed this
association (p<0.0001). INTERPRETATION: Wide variations in sedation and analgesia
practices occur between NICUs and countries. Widespread use of O-SH-GA in
intubated neonates might prolong their need for mechanical ventilation, but
further research is needed to investigate the therapeutic and adverse effects of
O-SH-GA in neonates, and to develop new and safe approaches for sedation and
analgesia. FUNDING: European Community's Seventh Framework Programme.
PMID- 26420025
TI - Polyol-enhanced dispersive liquid-liquid microextraction coupled with gas
chromatography and nitrogen phosphorous detection for the determination of
organophosphorus pesticides from aqueous samples, fruit juices, and vegetables.
AB - Polyol-enhanced dispersive liquid-liquid microextraction has been proposed for
the extraction and preconcentration of some organophosphorus pesticides from
different samples. In the present study, a high volume of an aqueous phase
containing a polyol (sorbitol) is prepared and then a disperser solvent along
with an extraction solvent is rapidly injected into it. Sorbitol showed the best
results and it was more effective on the extraction recoveries of the analytes
than inorganic salts such as sodium chloride, potassium chloride, and sodium
sulfate. Under the optimum extraction conditions, the method showed low limits of
detection and quantification within the ranges of 12-56 and 44-162 pg/mL,
respectively. Enrichment factors and extraction recoveries were in the ranges of
2799-3033 and 84-92%, respectively. The method precision was evaluated at a
concentration of 10 ng/mL of each analyte, and relative standard deviations were
found to be less than 5.9% for intraday (n = 6) and less than 7.8% for interday
(n = 4). Finally, some aqueous samples were successfully analyzed using the
proposed method and four analytes (diazinon, dimethoate, chlorpyrifos, and
phosalone) were determined, some of them at ng/mL level.
PMID- 26420026
TI - Sortilin-related receptor CNS expressed 2 (SorCS2) is localized to Bunina bodies
in amyotrophic lateral sclerosis.
AB - Sortilin-related receptor CNS expressed 2 (SorCS2) is one of the vacuolar protein
sorting 10 family proteins (VPS10Ps) that have pleiotropic roles in protein
trafficking and intracellular and intercellular signaling. Bunina bodies (BBs)
are specifically detected in the lower motor neurons in patients with amyotrophic
lateral sclerosis (ALS). BBs are immunolabeled with antibodies against cystatin
C, transferrin and peripherin and are considered to originate from the
endoplasmic reticulum, which is part of the protein sorting pathway. The present
study investigated whether VPS10Ps are involved in the formation of BBs in ALS.
We immunohistochemically examined the spinal cord from patients with ALS and
control subjects using antibodies against VPS10Ps (sortilin, SorLA, SorCS1,
SorCS2 and SorCS3). In normal controls, antibodies against VPS10Ps immunolabeled
the cytoplasm of anterior horn cells in a fine granular pattern. In ALS, almost
all BBs (95.1%) were strongly immunopositive for SorCS2, and immunoreativity for
sortilin and SorLA was decreased in anterior horn cells. These findings suggest
that VPS10Ps may be involved in the disease process of ALS.
PMID- 26420027
TI - Hyperforin alleviates mood deficits of adult rats suffered from early separation.
AB - In this study, we aimed to explore the effect of hyperforin (Hyp) on adult rats
suffered from early separation. Wistar infant rats were randomly divided into
three groups: control group (CON), early separation from parents group (ESP), and
early separation from parents+treatment with 3mg/kg/day Hyp group (ESP+Hyp).
Postnatal rats of ESP group and ESP+Hyp group were separated from their mothers
for 6h every day on the 14th day after birth, and this separation lasted for 3
weeks, while rats of CON group had no separation. Hyperforin was intragastric
administrated on the 21th day after birth, and lasted for 2 weeks in ESP+Hyp
group. After separation, adult rats were evaluated by using the open field test
(OFT), novelty suppressed feeding test (NSF) and forced swimming test (FST). In
OFT, time spent in central grids was much shorter in ESP group compared with that
of CON group. After treatment with hyperforin, time spent in central area was
much longer compared with that of ESP group. In NSF, the feeding latency of ESP
group was much longer than that of CON group. After treatment with hyperforin,
the feeding latency was shorter compared with that of ESP group. In FST, score of
ESP group was markedly higher than that of CON group. Interestingly, the score
was obviously lower in ESP+Hyp group than that of ESP group. In conclusion, these
results suggest that hyperforin is able to alleviate anxiety and remit depression
in ESP rats.
PMID- 26420028
TI - The expression levels of prolyl oligopeptidase responds not only to
neuroinflammation but also to systemic inflammation upon liver failure in rat
models and cirrhotic patients.
AB - BACKGROUND: Liver failure in experimental animals or in human cirrhosis elicits
neuroinflammation. Prolyl oligopeptidase (PREP) has been implicated in
neuroinflammatory events in neurodegenerative diseases: PREP protein levels are
increased in brain glial cells upon neuroinflammatory insults, but the
circulating PREP activity levels are decreased in multiple sclerosis patients in
a process probably mediated by bioactive peptides. In this work, we studied the
variation of PREP levels upon liver failure and correlated it with several
inflammatory markers to conclude on the relation of PREP with systemic and/or
neuroinflammation. METHODS: PREP enzymatic activity and protein levels measured
with immunological techniques were determined in the brain and plasma of rats
with portacaval shunt (PCS) and after treatment with ibuprofen. Those results
were compared with the levels of PREP measured in plasma from cirrhotic patients
with or without minimal hepatic encephalopathy (MHE). Levels of several pro
inflammatory cytokines and those of NO/cGMP homeostasis metabolites were measured
in PCS rats and cirrhotic patients to conclude on the role of PREP in
inflammation. RESULTS: In PCA rats, we found that PREP levels are significantly
increased in the hippocampus, striatum and cerebellum, that in the cerebellum the
PREP increase was significantly found in the extracellular space and that the
levels were restored to those measured in control rats after administration of an
anti-inflammatory agent, ibuprofen. In cirrhotic patients, circulatory PREP
activity was found to correlate to systemic and neuroinflammatory markers and had
a negative correlation with the severity of the disease, although no clear
relation to MHE. CONCLUSIONS: These results support the idea that PREP levels
could be used as indicators of cirrhosis severity in humans, and using other
markers, it might contribute to assessing the level of neuroinflammation in those
patients. This work reports, for the first time, that PREP is secreted to the
extracellular space in the cerebellum most probably due to glial activation and
supports the role of the peptidase in the inflammatory response.
PMID- 26420030
TI - Decanuclear Ln10 Wheels and Vertex-Shared Spirocyclic Ln5 Cores: Synthesis,
Structure, SMM Behavior, and MCE Properties.
AB - The reaction of a Schiff base ligand (LH3) with lanthanide salts, pivalic acid
and triethylamine in 1:1:1:3 and 4:5:8:20 stoichiometric ratios results in the
formation of decanuclear Ln10 (Ln = Dy (1), Tb (2), and Gd (3)) and pentanuclear
Ln5 complexes (Ln = Gd (4), Tb (5), and Dy (6)), respectively. The formation of
Ln10 and Ln5 complexes are fully governed by the stoichiometry of the reagents
used. Detailed magnetic studies on these complexes (1-6) have been carried out.
Complex 1 shows a SMM behavior with an effective energy barrier for the reversal
of the magnetization (Ueff) = 16.12(8) K and relaxation time (tauo) = 3.3*10(-5)
s under 4000 Oe direct current (dc) field. Complex 6 shows the frequency
dependent maxima in the out-of-phase signal under zero dc field, without
achieving maxima above 2 K. Complexes 3 and 4 show a large magnetocaloric effect
with the following characteristic values: -DeltaSm = 26.6 J kg(-1) K(-1) at T =
2.2 K for 3 and -DeltaSm = 27.1 J kg(-1) K(-1) at T = 2.4 K for 4, both for an
applied field change of 7 T.
PMID- 26420029
TI - First human case report of sepsis due to infection with Streptococcus suis
serotype 31 in Thailand.
AB - BACKGROUND: Streptococcus suis is a zoonotic pathogen that causes invasive
infections in humans and pigs. It has been reported that S. suis infection in
humans is mostly caused by serotype 2. However, human cases caused by other
serotypes have rarely been reported. This is the first report of a human case of
infection with S. suis serotype 31 in Thailand. CASE PRESENTATION: A 55-year-old
male alcohol misuser with liver cirrhosis was admitted with sepsis to a hospital
in the Central Region of Thailand. He had consumed a homemade, raw pork product
prior to the onset of illness. He was alive after treatment with ceftriaxone and
no complication occurred. An isolate from blood culture at the hospital was
suspected as viridans group Streptococcus. It was confirmed at a reference
laboratory as S. suis serotype 31 by biochemical tests, 16S rDNA sequencing, and
multiplex polymerase chain reaction for serotyping, but it was untypable by the
co-agglutination test with antisera against recognized S. suis serotypes,
suggesting loss of capsular material. The absence of a capsule was confirmed by
transmission electron microscopy. The isolate was confirmed to be sequence type
221, with 13 putative virulence genes that are usually found in serotype 2
strains. CONCLUSION: We should be aware of the emergence of S. suis infections
caused by uncommon serotypes in patients with predisposing conditions. Laboratory
capacity to identify S. suis in the hospital is needed in developing countries,
which can contribute to enhanced surveillance, epidemiological control, and
prevention strategies in the prevalent area.
PMID- 26420031
TI - Exome sequencing in a patient with Catel-Manzke-like syndrome excludes the
involvement of the known genes and reveals a possible candidate.
AB - In the present study we describe the exome sequencing and analysis of a patient
with Catel-Manzke-like phenotype showing bilateral hyperphalangism of the second
finger and thumb clinodactyly due to a unilateral delta phalanx, associated with
growth, cardiac and vertebral defects. The exome sequencing analysis excluded
pathogenetic mutations in the genes known to cause syndromes with hyperphalangism
and did not identify any alteration in the X-chromosome or de novo mutations in
likely candidate genes. Under the assumption of an autosomal recessive mode of
inheritance and based on the frequency of the single nucleotide variants found in
homozygous or double heterozygous states and the results of computer prediction
programs, only one gene, DNAH10, emerged as a candidate in the pathogenesis of
the disease in our patient. However, the differences among the known biological
functions of DNAH10 and the genes involved in the other syndromes with
hyperphalangism, suggest caution in the interpretation of the results.
PMID- 26420036
TI - Rapid and sensitive detection of carbapenemase activity in Acinetobacter
baumannii using superficially porous liquid chromatography-tandem mass
spectrometry.
AB - BACKGROUND: The emergence and spread of carbapenem-resistant Acinetobacter
baumannii poses a challenge for optimizing antibiotic therapies and preventing
outbreaks. Traditional phenotypic assays such as the modified Hodge test (MHT) or
polymerase chain reaction (PCR)-based detection of the carbapenemase genes are
time-consuming and complicated. Therefore, new approaches for the efficient
detection of carbapenemase-producing A. baumannii are urgently required. METHODS:
In this study, we used the superficially porous liquid chromatography-tandem mass
spectrometry (LC-MS/MS) assay to measure carbapenem hydrolysis in a solution
spiked with test strains of A. baumannii. The rate of carbapenem hydrolysis
during incubation was expressed as the ratio of the carbapenem peak area of the
test A. baumannii strains to the noncarbapenemase-producing A. baumannii ATCC
17978. This method can accurately measure the carbapenem hydrolysis rate and,
therefore, can effectively identify carbapenemase-producing strains within 75
minutes. RESULTS: A total of 112 A. baumannii strains were used in this study,
including 103 clinical isolates with 68 carbapenem-resistant strains and 35
carbapenem-susceptible strains, seven ATCC strains and two selected mutants. The
results of the superficially porous LC-MS/MS assay showed higher detection
sensitivity compared to the results of the MHT. CONCLUSION: Our results
demonstrate the ability of the former method to routinely detect carbapenemase
producing A. baumannii.
PMID- 26420037
TI - Comparison of Capability of Human Bone Marrow Mesenchymal Stem Cells and
Endometrial Stem Cells to Differentiate into Motor Neurons on Electrospun
Poly(epsilon-caprolactone) Scaffold.
AB - Human endometrial and bone marrow-derived mesenchymal stem cells can be
differentiated into a number of cell lineages. Mesenchymal stem cells (MSCs) are
potential candidates for cellular therapy. The differentiation of human bone
marrow MSCs (hBM-MSCs) and endometrial stem cells (hEnSCs) into motor neuron-like
cells has been rarely investigated previously; however, the comparison between
these stem cells when they are differentiated into motor neuron-like cell is yet
to be studied. The aim of this study was therefore to investigate and compare the
capability of hBM-MSCs and hEnSCs cultured on tissue culture polystyrene (TCP)
and poly epsilon-caprolactone (PCL) nanofibrous scaffold to differentiate into
motor neuron-like cells in the presence of neural inductive molecules. Engineered
hBM-MSCs and hEnSCs seeded on PCL nanofibrous scaffold were differentiated into
beta-tubulin III, islet-1, Neurofilament-H (NF-H), HB9, Pax6, and choactase
positive motor neurons by immunostaining and real-time PCR, in response to the
signaling molecules. The data obtained from PCR and immunostaining showed that
the expression of motor neuron markers of both hBM-MSCs and hEnSCs differentiated
cells on PCL scaffold are significantly higher than that of the control group.
The expression of these markers in hEnSCs differentiated cells was higher than
that in hBM-MSCs. However, this difference was not statistically significant. In
conclusion, differentiated hBM-MSCs and hEnSCs on PCL can provide a suitable
three-dimensional situation for neuronal survival and outgrowth for regeneration
of the central nervous system. Both cells may be potential candidates for
cellular therapy in motor neuron disorders. However, differentiation of hEnSCs
into motor neuron-like cells was better than hBM-MSCs.
PMID- 26420038
TI - Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation
and is guided by the microbiome.
AB - BACKGROUND: DNA methylation is an epigenetic mechanism central to development and
maintenance of complex mammalian tissues, but our understanding of its role in
intestinal development is limited. RESULTS: We use whole genome bisulfite
sequencing, and find that differentiation of mouse colonic intestinal stem cells
to intestinal epithelium is not associated with major changes in DNA methylation.
However, we detect extensive dynamic epigenetic changes in intestinal stem cells
and their progeny during the suckling period, suggesting postnatal epigenetic
development in this stem cell population. We find that postnatal DNA methylation
increases at 3' CpG islands (CGIs) correlate with transcriptional activation of
glycosylation genes responsible for intestinal maturation. To directly test
whether 3' CGI methylation regulates transcription, we conditionally disrupted
two major DNA methyltransferases, Dnmt1 or Dnmt3a, in fetal and adult intestine.
Deficiency of Dnmt1 causes severe intestinal abnormalities in neonates and
disrupts crypt homeostasis in adults, whereas Dnmt3a loss was compatible with
intestinal development. These studies reveal that 3' CGI methylation is
functionally involved in the regulation of transcriptional activation in vivo,
and that Dnmt1 is a critical regulator of postnatal epigenetic changes in
intestinal stem cells. Finally, we show that postnatal 3' CGI methylation and
associated gene activation in intestinal epithelial cells are significantly
altered by germ-free conditions. CONCLUSIONS: Our results demonstrate that the
suckling period is critical for epigenetic development of intestinal stem cells,
with potential important implications for lifelong gut health, and that the gut
microbiome guides and/or facilitates these postnatal epigenetic processes.
PMID- 26420040
TI - A cross-sectional study of the magnitude, barriers, and outcomes of HIV status
disclosure among women participating in a perinatal HIV transmission study, "the
Nevirapine Repeat Pregnancy study".
AB - BACKGROUND: HIV status disclosure is a difficult emotional task for HIV-infected
persons and may create the opportunity for both social support and rejection. In
this study, we evaluated the proportions, patterns, barriers and outcomes of HIV-
1 status disclosure among a group of women in Uganda. METHODS: An exit interview
was conducted one year post-partum for 85 HIV-infected women who participated in
a study of HIV-1 transmission rates among NVP-experienced compared with NVP-naive
women in "The Nevirapine Repeat Pregnancy (NVP-RP) Study" at the Makerere
University-Johns Hopkins University Research Collaboration, Kampala-Uganda,
between June 2004 and June 2006. RESULTS: Of the 85 women interviewed, 99 % had
disclosed their HIV status to at least one other person. Disclosure proportions
ranged between 1 % to employer(s) and 69 % to a relative other than a parent.
Only 38 % of the women had disclosed to their sex partners. Women with an HIV
infected baby were more likely than those with an uninfected baby to disclose to
their sex partner, OR 4.9 (95 % CI, 2.0 -11.2), and women were less likely to
disclose to a partner if they had previously disclosed to another relative than
if they had not, OR 0.19 (95 % CI, 0.14-0.52). The most common reasons for non
disclosure included fear of separation from the partner and subsequent loss of
financial support 34 %, and not living with the partner (not having opportunities
to disclose) 26 %. While most women (67 %) reported getting social support
following disclosure, 22 % reported negative outcomes (neglect, separation from
their partners, and loss of financial support). Following disclosure of HIV
status, 9 % of women reported that their partner (s) decided to have an HIV test.
CONCLUSION: Results from this study show high overall HIV disclosure proportions
and how this disclosure of HIV status can foster social support. However,
proportions of disclosure specifically to male sex partners were low, which
suggests the need for interventions aimed at increasing male involvement in
perinatal care, along with supportive counseling.
PMID- 26420042
TI - How To Form a Phosphate Anhydride Linkage in Nucleotide Derivatives.
AB - The fundamental roles of nucleoside triphosphates and nucleotide cofactors such
as NAD(+) in biochemistry are well known. In recent decades, continuing research
has revealed the key role of 5'-capped RNA and 5',5'-dinucleoside polyphosphates
in the regulation of vitally important physiological processes. Last but not
least, the commercial potential of nucleoside triphosphate synthesis can hardly
be overestimated. Nevertheless, despite decades of investigation and the obvious
topicality of the research on the chemical synthesis of the nucleotide compounds
containing phosphate anhydride linkages, none of the existing procedures can be
considered an up-to-date "gold standard". However, there are a number of fruitful
synthetic approaches to forming phosphate anhydride linkages in satisfactory
yield. These are summarized in this concise review, organized by the type of
active phosphorous intermediate and reagents used.
PMID- 26420039
TI - Urokinase-type plasminogen activator receptor interaction with beta1 integrin is
required for platelet-derived growth factor-AB-induced human mesenchymal
stem/stromal cell migration.
AB - INTRODUCTION: Mesenchymal stem cells (MSC) are well described for their role in
tissue regeneration following injury. Migratory properties of endogenous or
administrated MSC are critical for tissue repair processes. Platelet-derived
growth factor (PDGF) is a chemotactic growth factor that elicits mesenchymal cell
migration. However, it is yet to be elucidated if signaling pathways other than
direct activation of PDGF receptor (PDGF-R) are involved in PDGF-induced cell
migration. METHODS: Knocking down and co-immunoprecipitation approaches were used
to evaluate urokinase-type plasminogen activator receptor (uPAR) requirement and
its interactions with proteins involved in migration mechanisms, in human MSC
induced to migrate under PDGF-AB effect. RESULTS: We demonstrated that uPAR
activation and its association with beta1-integrin are required for PDGF-AB
induced migration. This phenomenon takes place in MSC derived from bone marrow
and from adipose tissue. CONCLUSIONS: We showed that PDGF-AB downstream signaling
requires other effector molecules in MSC such as the uPA/uPAR system and beta1
integrin signaling pathway known for their role in migration. These findings
provide new insights in molecular mechanisms of PDGF-AB-induced migration of
human MSC that may be relevant to control MSC function and tissue remodeling
after injury.
PMID- 26420041
TI - 3D fibre deposition and stereolithography techniques for the design of
multifunctional nanocomposite magnetic scaffolds.
AB - Magnetic nanocomposite scaffolds based on poly(epsilon-caprolactone) and
poly(ethylene glycol) were fabricated by 3D fibre deposition modelling (FDM) and
stereolithography techniques. In addition, hybrid coaxial and bilayer magnetic
scaffolds were produced by combining such techniques. The aim of the current
research was to analyse some structural and functional features of 3D magnetic
scaffolds obtained by the 3D fibre deposition technique and by stereolithography
as well as features of multimaterial scaffolds in the form of coaxial and bilayer
structures obtained by the proper integration of such methods. The compressive
mechanical behaviour of these scaffolds was investigated in a wet environment at
37 degrees C, and the morphological features were analysed through scanning
electron microscopy (SEM) and X-ray micro-computed tomography. The capability of
a magnetic scaffold to absorb magnetic nanoparticles (MNPs) in water solution was
also assessed. confocal laser scanning microscopy was used to assess the in vitro
biological behaviour of human mesenchymal stem cells (hMSCs) seeded on 3D
structures. Results showed that a wide range of mechanical properties, covering
those spanning hard and soft tissues, can be obtained by 3D FDM and
stereolithography techniques. 3D virtual reconstruction and SEM showed the
precision with which the scaffolds were fabricated, and a good-quality interface
between poly(epsilon-caprolactone) and poly(ethylene glycol) based scaffolds was
observed for bilayer and coaxial scaffolds. Magnetised scaffolds are capable of
absorbing water solution of MNPs, and a preliminary information on cell adhesion
and spreading of hMSCs was obtained without the application of an external
magnetic field.
PMID- 26420043
TI - Hundreds of unnecessary surgeries were done by physician assistant in $150m
fraud.
PMID- 26420044
TI - Precise colloids with tunable interactions for confocal microscopy.
AB - Model colloidal systems studied with confocal microscopy have led to numerous
insights into the physics of condensed matter. Though confocal microscopy is an
extremely powerful tool, it requires a careful choice and preparation of the
colloid. Uncontrolled or unknown variations in the size, density, and composition
of the individual particles and interactions between particles, often influenced
by the synthetic route taken to form them, lead to difficulties in interpreting
the behavior of the dispersion. Here we describe the straightforward synthesis of
copolymer particles which can be refractive index- and density-matched
simultaneously to a non-plasticizing mixture of high dielectric solvents. The
interactions between particles are accurately tuned by surface grafting of
polymer brushes using Atom Transfer Radical Polymerization (ATRP), from hard
sphere-like to long-ranged electrostatic repulsion or mixed charge attraction. We
also modify the buoyant density of the particles by altering the copolymer ratio
while maintaining their refractive index match to the suspending solution
resulting in well controlled sedimentation. The tunability of the inter-particle
interactions, the low volatility of the solvents, and the capacity to
simultaneously match both the refractive index and density of the particles to
the fluid opens up new possibilities for exploring the physics of colloidal
systems.
PMID- 26420045
TI - Assessment of the psychometric properties of the Chinese Impact of Vision
Impairment questionnaire in a population-based study: findings from the Singapore
Chinese Eye Study.
AB - PURPOSE: We investigated whether the Chinese impact of vision impairment (IVI)
questionnaire is valid to generate reliable person estimates in a population
based sample. METHODS: VRQoL was measured using the 32-item Chinese version of
the IVI questionnaire in the Singapore Chinese Eye Study (2009-2011), a
population-based study of the prevalence and risk factors for VI and eye diseases
in Chinese Singaporeans. Rasch analysis was used to assess the Chinese IVI's
response category functioning, precision, unidimensionality, targeting and
differential item functioning. The ability of the Chinese IVI to discriminate
participants along the spectrum of VI demonstrated criterion validity. RESULTS:
Of the 3353 participants, 27.2 % (n = 912) had VI (presenting visual acuity
<6/12, better eye). Response categories were collapsed from six to four to
resolve disordered thresholds. The Chinese IVI initially demonstrated
multidimensionality and was split into three scales: 'Reading and Accessing
Information'; 'Mobility and Independence'; and 'Emotional Well-being'. All three
scales were unidimensional and demonstrated excellent range-based precision (all
reliability coefficients 0.97), following removal of three misfitting items. Mean
person measures decreased with worsening VI (e.g. Reading: none (7.50 logits);
mild (6.99 logits); moderate (6.44 logits); and severe (3.01 logits) VI; p <
0.001). CONCLUSIONS: A three-dimensional 29-item Chinese IVI is a valid tool to
assess the impact of VI on VRQoL in a large population-based sample, comprising
over a quarter of participants with VI. The 28-item English IVI is also likely to
be valid for use in population-based studies; however, this must be demonstrated
empirically in future studies.
PMID- 26420046
TI - Initiation of medications for Parkinson's disease: a qualitative description.
AB - AIMS AND OBJECTIVES: To understand experiences of people with Parkinson's disease
to initiate medication therapy for Parkinson's disease. BACKGROUND: Nonadherence
to medication regimens and reluctance to initiate medication therapy among people
with Parkinson's disease has been documented in previous research. However,
little is known about experiences and decisions of people with Parkinson's
disease to initiate antiparkinsonian medications and their beliefs or levels of
understanding of antiparkinsonian medications in the USA. DESIGN: An exploratory,
descriptive qualitative study was employed. METHODS: Semi-structured interviews
were conducted with 16 community-dwelling individuals with Parkinson's disease
(69% male) and five family caregivers (40% male). Data analysis was performed
using content analysis. RESULTS: Two domains emerged from the data: decision
making to initiate antiparkinsonian medications as prescribed and reasons to
delay initiation of levodopa to a later stage of Parkinson's disease.
CONCLUSIONS: Acceptance of antiparkinsonian medications at the early stage of
Parkinson's disease was influenced by the trusting relationship between
participants and their health care provider. Fear of levodopa's long-term side
effects led to acceptance of non-levodopa therapies first. Complementary and
Alternative Medicine was used to manage Parkinson's disease symptoms among
participants who delayed antiparkinsonian medication therapy. RELEVANCE TO
CLINICAL PRACTICE: Nurses may have a role to assess individuals' beliefs and
concerns about antiparkinsonian medication therapy and to provide adequate
information to assist with the decision about Parkinson's disease symptom
management.
PMID- 26420047
TI - Potential of Submergedly Cultivated Mycelia of Ganoderma spp. as Antioxidant and
Antimicrobial Agents.
AB - The study aimed to evaluate the antiradical and antimicrobial (antibacterial and
antifungal) potentials of ethanol mycelial extracts of selected Ganoderma species
and strains and to define interand intraspecies diversity among Ganoderma species
and strains. Ganoderma lucidum strains were good DPPH* scavengers (neutralizing
up to 57.12% radicals), contrary to G. applanatum (20.35%) and G. carnosum
(17.04%). High correlations between the activities and contents of total phenols
in the extracts showed that these compounds were carriers of the activity.
Results obtained by both discdiffusion and microdilution methods indicated that
the extract of G. lucidum BEOFB 433 was the most potent antibacterial agent that
inhibited growth of almost all bacterial species at a concentration of 1.0 mg/mL.
Salmonella typhimurium was the most sensitive species to the mycelium extracts.
Extracts of G. lucidum BEOFB 431 and BEOFB 434 showed the best antifungal
activity since in concentration of 0.5 mg/mL inhibited the growth of Aspergillus
glaucus (BEOFB 431) and the growth of A. glaucus and Trichoderma viride (BEOFB
434). Extracts of G. applanatum and G. lucidum BEOFB 431 had the strongest
fungicidal effects, with lethal outcomes for A. glaucus and T. viride,
respectively, being noted at a concentration of 1.17 mg/mL. Aspergillus niger was
proved as the most resistant species.
PMID- 26420048
TI - Bioremediation of Carbendazim, a Benzimidazole Fungicide Using Brevibacillus
borstelensis and Streptomyces albogriseolus Together.
AB - Excessive use of pesticides in agriculture has resulted in contamination of water
resources, air, soil and disruption of biogeochemical cycles. These compounds
adversely affect humans and animal health, helpful soil microbes and crop
production as well. Biodegradation of pesticides by microbes exists in a number
of habitats like soil, sediments, surface, ground water, and sludge, etc. In the
present study, efforts were made to develop a microbial consortium comprising of
Streptomyces albogriseolus and Brevibacillus borstelensis strains isolated
earlier which are capable of degrading carbendazim, a benzimidazole fungicide and
making it harmless. Both the strains Brevibacillus borstelensis and Streptomyces
albogriseolus displayed growth even at higher concentrations (500MUg mL(-1)) of
carbendazim. The consortium containing Brevibacillus borstelensis and
Streptomyces albogriseolus reduced carbendazim concentration from 30 ug mL(-1) to
0.86 ug mL(-1) (nearly 97%) in 12hrs to 0.60 ug mL(-1) (~98%) in 20 hrs as
determined by LCMS analysis. There was a significant reduction observed in
carbendazim concentration than reduction obtained when individual strain was
used. This study paves a way for further exploration of degradation mechanism at
the genetic level to enhance the capability of microorganisms in consortia.
PMID- 26420049
TI - Triptolide Induces Cell Apoptosis by Targeting H3K4me3 and Downstream Effector
Proteins in KM3 Multiple Myeloma Cells.
AB - As the principal active ingredient in the Chinese herb Tripterygium wilfordii
Hook.F (TwHF), triptolide has been shown to have very strong antitumor
properties. The trimethylation of lysine 4 on histone H3 (H3K4me3) has been
proposed to promote gene expression, and the accumulation of H3K4me3 at the
transcriptional start sites of oncogenes is involved in carcinogenesis. To
identify the association between the reduction of H3K4me3 and the apoptosis of MM
cells induced by triptolide, we investigated the global patterns of H3K4me3
occupancy in the MM cell genome. Combined analyses using ChIP-on-chip and western
blotting showed that H3K4me3 were highly enriched on the gene promoters of c-Myc
and VEGFA and were associated with the up-regulation of both genes. Treatment of
KM3 cells with triptolide and siRNA targeting ASH2L reduced the expression of c
Myc and VEGFA. These results suggest that triptolide can down-regulate c-Myc and
VEGFA expression by blocking the accumulation of H3K4me3 on their promoters,and
thus play an important role in anti-MM mechanism.
PMID- 26420050
TI - Nutrition in Allogeneic Stem Cell Transplantion--Clinical Guidelines and
Immunobiological Aspects.
AB - Even though malnutrition is associated with an adverse prognosis after allogeneic
stem cell transplantation, few studies have addressed the question what is the
optimal nutritional support for these patients. There is a general agreement that
the body weight, body mass index and nutritional intake can be used to guide the
post-transplant nutritional support; enteral nutrition may then be tried but most
patients will require parenteral nutrition. There is no scientific basis for
further standardization of post-transplant nutritional support. The nutritional
status with regard to amino acid as well as fatty acid metabolism and vitamin
levels are important for immunoregulation. Several amino acids and their
metabolites function as signaling molecules through their binding to specific
receptors, and they are thereby become important both in dendritic cell
differentiation and T cell activation and the metabolic switch that often occurs
during the activation of immunocompetent cells. We review previous studies of
nutritional support in allotransplant recipients and discuss possible molecular
mechanisms involved in metabolic immunoregulation and the development of post
transplant immune-mediated complications.
PMID- 26420051
TI - Development of Personalized Molecular Therapy for Acute Myeloid Leukemia.
AB - Acute myeloid leukemia (AML) is characterized by extensive clinical and
biological heterogeneity. Despite vast advances in understanding the molecular
pathology in AML during the last two decades few new AML therapeutics have been
approved by the European Medicines Agency. Since 2005 only the epigenetic
modulators decitabine and azacytidine, as well as histamine (plus interleukin- 2)
have been approved against AML. None of these have outstanding efficiency, and
decitabine and azacytdine have only been incorporated in frontline therapy of AML
with limited enthusiasm. The majority of AML patients are frail and elderly, and
lack of mild but effective agents for this patient cohort constitutes a major
unmet need as overall survival remains poor. Along with the recent advancements
in the molecular characterization of AML, numerous targeted therapies have been
tested in clinical trials. In this review, we discuss the biological rationale
for a selection of these novel therapeutic approaches, including epigenetic
modifiers, agents targeting signalling pathways and inhibitors of nuclear
cytoplasmic shuttling. Further we discuss some of the possible shortcomings in
current trial design that could explain the apparent incoherence between our
improved biological knowledge and the lack of progress in therapy development of
AML.
PMID- 26420052
TI - Features and outcomes of pediatric early T cell leukemia: King Hussein Cancer
Center experience.
PMID- 26420054
TI - Changes in levels of apoptosis in the walls of different segments of great
saphenous varicose veins.
AB - OBJECTIVE: Disordered programmed cell death may play a role in the development of
superficial venous incompetence. We have determined the number of cells
undergoing apoptosis and the alterations in the apoptotic level in the wall of
different segments of the great saphenous varicose vein. METHODS: Twenty-one
varicose great saphenous veins (VGSVs) (varicose group) and 12 normal great
saphenous veins (GSVs) (control group) were collected, and the apoptosis level in
the upper, middle, and lower segments were immunohistochemically stained with
antibodies (anti-Bax and anti-Bcl-xl). Apoptosis was evaluated by the TUNEL assay
and immunofluorescence staining. The morphology of apoptotic cells was observed
with an electron microscope. RESULTS: Quantitative analysis showed that the
apoptotic ratios in venous walls (intima and media) of the varicose group were
significantly lower than the corresponding regions in the control group (all P <
0.05). A significantly higher apoptotic rates of the venous walls was observed in
control group within the upper compared with the lower segment (P < 0.05).
Significantly higher positive proteins expression rates of Bcl-xl/Bax were also
detected in the VGSVs compared with the GSVs within the three segments,
respectively (P < 0.01). Electron microscopic observations confirmed that
endothelial and smooth muscle cells in varicose and normal vein walls exhibited
apoptotic morphologic features, such as fuzzy mitochondrial cristae, medullary
changes, and margination of the nuclear chromatin. CONCLUSION: VGSV walls were
found to have a significant decrease in apoptotic rate compared with that of
GSVs. The rate of apoptosis in the intima and media within the upper segment was
increased more than the middle and lower segments in the GSVs. Our findings
confirm that programmed cell death is down-regulated in primary varicose veins.
PMID- 26420053
TI - Association of polymorphisms near the FOXC2 gene with the risk of varicose veins
in ethnic Russians.
AB - OBJECTIVE: To investigate the association of polymorphisms located near the FOXC2
gene with the risk of varicose veins in ethnic Russians. METHODS: Allele,
genotype, and haplotype frequencies were determined in the sample of 474 patients
with primary varicose veins and in the control group of 478 individuals without a
history of chronic venous disease. RESULTS: Polymorphisms rs7189489, rs4633732,
and rs1035550 showed the association with the increased risk of varicose veins,
but none of the observed associations remained significant after correction for
multiple testing. Haplotype analysis revealed the association of haplotype
rs7189489 C-rs4633732 T-rs34221221 C-rs1035550 C-rs34152738 T-rs12711457 G with
the increased risk of varicose veins (OR = 2.67, P = 0.01). CONCLUSIONS: Our
results provide evidence that the studied polymorphisms do not play a major role
in susceptibility to varicose veins development in the Russian population.
PMID- 26420056
TI - How TK-TD and population models for aquatic macrophytes could support the risk
assessment for plant protection products.
AB - This case study of the Society of Environmental Toxicology and Chemistry (SETAC)
workshop MODELINK demonstrates the potential use of mechanistic effects models
for macrophytes to extrapolate from effects of a plant protection product
observed in laboratory tests to effects resulting from dynamic exposure on
macrophyte populations in edge-of-field water bodies. A standard European Union
(EU) risk assessment for an example herbicide based on macrophyte laboratory
tests indicated risks for several exposure scenarios. Three of these scenarios
are further analyzed using effect models for 2 aquatic macrophytes, the free
floating standard test species Lemna sp., and the sediment-rooted submerged
additional standard test species Myriophyllum spicatum. Both models include a
toxicokinetic (TK) part, describing uptake and elimination of the toxicant, a
toxicodynamic (TD) part, describing the internal concentration-response function
for growth inhibition, and a description of biomass growth as a function of
environmental factors to allow simulating seasonal dynamics. The TK-TD models are
calibrated and tested using laboratory tests, whereas the growth models were
assumed to be fit for purpose based on comparisons of predictions with typical
growth patterns observed in the field. For the risk assessment, biomass dynamics
are predicted for the control situation and for several exposure levels. Based on
specific protection goals for macrophytes, preliminary example decision criteria
are suggested for evaluating the model outputs. The models refined the risk
indicated by lower tier testing for 2 exposure scenarios, while confirming the
risk associated for the third. Uncertainties related to the experimental and the
modeling approaches and their application in the risk assessment are discussed.
Based on this case study and the assumption that the models prove suitable for
risk assessment once fully evaluated, we recommend that 1) ecological scenarios
be developed that are also linked to the exposure scenarios, and 2) quantitative
protection goals be set to facilitate the interpretation of model results for
risk assessment.
PMID- 26420057
TI - A Cs(x)WO3/ZnO nanocomposite as a smart coating for photocatalytic environmental
cleanup and heat insulation.
AB - A novel CsxWO3/ZnO smart coating was proposed to achieve multiple functions, such
as heat insulation, photodecomposition of toxic NO gas, blocking of harmful UV
light, etc. In this composite coating, CsxWO3 nanorods were used as a NIR and UV
light shielding material while ZnO nanoparticles were utilized as a photocatalyst
and a material to enhance visible light transmittance and block UV light. When
the mass ratio of CsxWO3/ZnO was 1, the composite coating possessed a very good
visible light transmittance of over 80% and an excellent UV-shielding ability.
This novel coating showed heat insulation that is superior to the ITO coating and
photocatalytic decontamination of NO gas that is superior to the standard TiO2
(P25). The proposed CsxWO3/ZnO smart coating is a promising material not only for
energy saving but also for environmental cleanup.
PMID- 26420055
TI - Use of Focus Groups to Inform a Youth Diabetes Prevention Model.
AB - OBJECTIVE: To explore minority adolescents' perceptions of their diabetes risk,
barriers and facilitators to adopting lifestyle changes, and ideas for adapting a
youth diabetes prevention model. METHODS: The study was conducted at
collaborating community sites in East Harlem, NY. Trained moderators facilitated
focus groups, which were audio taped and transcribed. Participants were 21 Latino
and African American adolescents aged 14-18 years with a family history of
diabetes and no reported personal history of diabetes. The phenomenon of interest
was youth input in adapting a diabetes prevention model. Two researchers
independently coded transcripts, identified major themes, compared findings, and
resolved differences through discussion and consensus. RESULTS: Dominant themes
included (1) the impact of diabetes on quality of life within adolescents'
personal networks; (2) conflict between changing diet and activity and their
current lifestyle; (3) lifestyle choices being dictated by cost, mood, body
image, and environment, not health; and (4) family, social, and environmental
pressures reinforcing sedentary behaviors and unhealthy diets. CONCLUSIONS AND
IMPLICATIONS: Themes from youth focus groups were framed in the context of an
existing youth diabetes prevention conceptual model, with results informing
expansion of the model and identification and organization of potential
intervention components.
PMID- 26420059
TI - Multiple Bonds between Main-Group Elements and Transition Metals. 136.
"Polymerization" of an Organometal Oxide: The Unusual Behavior of
Methyltrioxorhenium(VII) in Water.
PMID- 26420058
TI - A diphtheria toxin resistance marker for in vitro and in vivo selection of stably
transduced human cells.
AB - We developed a selectable marker rendering human cells resistant to Diphtheria
Toxin (DT). The marker (DT(R)) consists of a primary microRNA sequence engineered
to downregulate the ubiquitous DPH2 gene, a key enzyme for the biosynthesis of
the DT target diphthamide. DT(R) expression in human cells invariably rendered
them resistant to DT in vitro, without altering basal cell growth. DT(R)-based
selection efficiency and stability were comparable to those of established drug
resistance markers. As mice are insensitive to DT, DT(R)-based selection can be
also applied in vivo. Direct injection of a GFP-DT(R) lentiviral vector into
human cancer cell-line xenografts and patient-derived tumorgrafts implanted in
mice, followed by systemic DT administration, yielded tumors entirely composed of
permanently transduced cells and detectable by imaging systems. This approach
enabled high-efficiency in vivo selection of xenografted human tumor tissues
expressing ectopic transgenes, a hitherto unmet need for functional and
morphological studies in laboratory animals.
PMID- 26420060
TI - Software development for estimating the concentration of radioactive cesium in
the skeletal muscles of cattle from blood samples.
AB - The 2011 earthquake severely damaged the Fukushima Daiichi Nuclear Power Plant
(FNPP), resulting in the release of large quantities of radioactive material into
the environment. The deposition of these radionuclides in rice straw as livestock
feed led to the circulation of contaminated beef in the market. Based on the
safety concern of the consumers, a reliable method for estimating concentrations
of radioactive cesium in muscle tissue is needed. In this study, we analyzed the
concentrations of radioactive cesium in the blood and skeletal muscle of 88
cattle, and detected a linear correlation between them. We then developed
software that can be used to estimate radioactive cesium concentrations in muscle
tissue from blood samples. Distribution of this software to the livestock
production field would allow us to easily identify high-risk cattle, which would
be beyond the safety regulation, before shipping out to the market. This software
is planned to be released as freeware. This software would contribute to food
safety, and aid the recovery of the livestock industry from the damage creacted
by the 2011 Tohoku earthquake and tsunami.
PMID- 26420061
TI - Lack of survival improvement with novel anti-myeloma agents for patients with
multiple myeloma and central nervous system involvement: the Greek Myeloma Study
Group experience.
AB - Involvement of the central nervous system (CNS) is a rare complication of
multiple myeloma (MM). Herein, we have described the incidence, characteristics,
prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored
the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this
setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed
symptomatic MM patients, consecutively diagnosed and treated during the same
period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years,
range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS
MM diagnosis 29 months). Clinical and laboratory characteristics were
retrospectively recorded. Twenty-six percent of patients had circulating plasma
cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived
plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS
MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional
radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM
survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients
treated with NA and/or radiotherapy vs. others. In the multivariate analysis,
prior treatment of MM with NA, extramedullary disease (EMD) during MM course
(i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH
at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM
with NA did not predict for post CNS-MM survival. Despite the relatively limited
number of patients due to the rarity of CNS-MM, our results suggest that NA do
not seem to improve post CNS-MM survival. Patients with EMD display shortened
post CNS-MM survival and should be followed thoroughly.
PMID- 26420062
TI - A randomized clinical trial on the effectiveness of an intervention to treat
psychological distress and improve quality of life after autologous stem cell
transplantation.
AB - Psychological distress contributes to impaired quality of life in hematological
cancer patients. Stepped care treatment, in which patients start with the least
intensive treatment most likely to work and only receive more intensive
interventions if needed, could improve distress. We aimed to evaluate the outcome
of stepped care treatment on psychological distress and physical functioning in
patients treated with autologous stem cell transplantation for hematological
malignancies. In the present study, we performed a randomized clinical trial with
two treatment arms: stepped care and care as usual. Baseline assessment and
randomization occurred during pre-transplant hospitalization. Stepped care was
initiated after 6 weeks, consisting of (1) watchful waiting, (2) Internet-based
self-help intervention, and (3) face-to-face counseling/ psychopharmacological
treatment/ referral. Follow-up measurements were conducted at 13, 30, and 42
weeks after transplantation. Stepped care (n = 47) and care as usual (n = 48)
were comparable on baseline characteristics. The uptake of the intervention was
low: 24 patients started with step 1, 23 with step 2, and none with step 3.
Percentages of distressed patients ranged from 4.1 to 9.7 %. Ten percent of
patients received external psychological or psychiatric care. No statistically
significant differences were found between stepped care and care as usual on
psychological distress or physical functioning in intention to treat analyses,
nor in per protocol analyses. The stepped care program was not effective in
decreasing psychological distress. The low intervention uptake, probably related
to the low levels of psychological distress, offers an explanation for this
outcome. Future research should take into account patients' specific care needs.
Netherlands Trial Registry identifier: NTR1770.
PMID- 26420064
TI - Adsorption of Lead Ions from Aqueous Phase on Mesoporous Silica with P-Containing
Pendant Groups.
AB - Mesoporous silica materials with hydroxyphosphatoethyl pendant groups (POH-MS)
were obtained by a two-step process: (1) block copolymer Pluronic P123-templated
synthesis of mesoporous silica with diethylphosphatoethyl groups (DP-MS) by co
condensation of diethylphosphatoethyl triethoxysilane (DPTS) and
tetraethylorthosilicate (TEOS) under acidic conditions and (2) conversion of
diethylphosphatoethyl into hydroxyphosphatoethyl groups upon suitable treatment
with concentrated hydrochloric acid. The DP-MS samples obtained by using up to
20% of DPTS featured hexagonally ordered mesopores, narrow pore size distribution
and high specific surface area. Conversion of DP-MS to mesoporous silica with
hydroxyphosphatoethyl groups (POH-MS) resulted in the enlargement of the specific
surface area, total porosity, and microporosity. High affinity of
hydroxyphosphatoethyl groups toward lead ions (Pb(2+)) makes the POH-MS materials
attractive sorbents for lead ions, which is reflected by high lead uptake
reaching 272 mg of Pb(2+) per gram of POH-MS. This study shows that the simple
and effective co-condensation strategy assures high loading of P-containing
groups showing high affinity toward lead ions, which is of great importance for
removal of highly toxic lead ions from contaminated water.
PMID- 26420063
TI - [Direct oral anticoagulation and gastrointestinal bleeding: Interventional
therapy management].
AB - BACKGROUND: More and more patients are being treated with direct oral
anticoagulants (DOAC). Under treatment with DOACs gastrointestinal bleeding
appears to occur more frequently, particularly in the lower gastrointestinal
tract, compared to treatment with vitamin K antagonists (e.g. warfarin).
OBJECTIVE: A possible approach should now be elaborated in a joint effort by
gastroenterologists and cardiologists. MATERIAL AND METHODS: A selective
literatue search was carried out and own experiences were also included. RESULTS:
The decision to perform procoagulant therapy by slowly injecting 30-50 IU
prothrombin complex concentrate (PPSB) per kg body weight intravenously depends
on various factors and should be assessed critically. Specific antidotes are
awaiting approval. After a bleeding episode potentially controllable and
reversible triggers must be excluded (e.g. drug interactions and renal
impairment). The risk of recurrent bleeding and the risk of thromboembolic events
have to be weighed against each other before deciding to readminister an
anticoagulant and its form. Dose reduction and changing to apixaban (in reduced
dosage) are options for risk reduction and vitamin K antagonists can also be
considered. DISCUSSION: It is still unclear what role specific antidotes will
play.
PMID- 26420066
TI - Benzophenone and its analogs bind to human glyoxalase 1.
AB - Benzophenone is a popular photophore for photoaffinity-labeling. It is also an
important framework for drug development; many drugs contain benzophenone or
analogous frameworks. The current work reports that benzophenone and its analogs
bind to human glyoxalase 1. The binding, however, has little effect on the
catalytic activity of this enzyme. The implications of the finding in terms of
both drug development and photoaffinity-labeling are discussed.
PMID- 26420065
TI - PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating
cells.
AB - Tumour-initiating cells (TICs) are advocated to constitute the sustaining force
to maintain and renew fully established malignancy; however, the molecular
mechanisms responsible for these properties are elusive. We previously
demonstrated that voltage-gated calcium channel alpha2delta1 subunit marks
hepatocellular carcinoma (HCC) TICs. Here we confirm directly that alpha2delta1
is a HCC TIC surface marker, and identify let-7c, miR-200b, miR-222 and miR-424
as suppressors of alpha2delta1(+) HCC TICs. Interestingly, all the four miRNAs
synergistically target PBX3, which is sufficient and necessary for the
acquisition and maintenance of TIC properties. Moreover, PBX3 drives an essential
transcriptional programme, activating the expression of genes critical for HCC
TIC stemness including CACNA2D1, EpCAM, SOX2 and NOTCH3. In addition, the
expression of CACNA2D1 and PBX3 mRNA is predictive of poor prognosis for HCC
patients. Collectively, our study identifies an essential signalling pathway that
controls the switch of HCC TIC phenotypes.
PMID- 26420068
TI - All-metallagermoxane with an adamantanoid cage structure: [(Cp*Ru(CO)2Ge)4(MU
O)6] (Cp* = eta(5)-C5Me5).
AB - In an attempt to synthesize a zero valent germanium compound, we have carried out
the reaction of [(Cp*RuCO)(GeCl2)]2, 1 with potassium metal that led to the
formation of a metallagermoxane [(Cp*Ru(CO)2Ge)4(MU-O)6], 2. Compound 2 is the
first example of a tetrametallagermoxane with an exo-{Cp*Ru(CO)2} fragment. DFT
calculations were used to examine the key intermediates associated with the
formation of 2.
PMID- 26420067
TI - New SIRT1 activator from alkaline hydrolysate of total saponins in the stems
leaves of Panax ginseng.
AB - Two new dammarane-type triterpenes, namely ginsenoslaloside-I [3beta,12beta,24S
trihydroxy-dammara-20(22)E,25-diene-3-O-beta-D-glucopyranoside, 1] and 20(S)
ginsenoside-Rh1-6'-acetate (2), together with twelve known compounds (3-14) were
isolated from the alkaline hydrolysate of total saponins of the stems-leaves of
Panax ginseng C.A. Meyer. Their chemical structures were elucidated by extensive
spectroscopic analyses and comparison with the reported data. All 14 compounds
were evaluated for their anti-proliferative activities against two human cancer
cell lines (HL-60 and Hep-G2) and promotion activities of SIRT1. Compound 6
exhibited significant inhibitory activity in a concentration-dependent manner
against HL-60 and Hep-G2 with the IC50 values of 10.32 and 24.33MUM,
respectively, and had comparable IC50 values with those of vinorelbine, a
positive control agent. Meanwhile, compounds 1 and 6 were found to be a potential
activator of SIRT1. The preliminary structure-activity relationship was also
discussed based on the experimental data obtained.
PMID- 26420069
TI - What factors control superficial lava dome explosivity?
AB - Dome-forming eruption is a frequent eruptive style and a major hazard on numerous
volcanoes worldwide. Lava domes are built by slow extrusion of degassed, viscous
magma and may be destroyed by gravitational collapse or explosion. The triggering
of lava dome explosions is poorly understood: here we propose a new model of
superficial lava-dome explosivity based upon a textural and geochemical study
(vesicularity, microcrystallinity, cristobalite distribution, residual water
contents, crystal transit times) of clasts produced by key eruptions. Superficial
explosion of a growing lava dome may be promoted through porosity reduction
caused by both vesicle flattening due to gas escape and syn-eruptive cristobalite
precipitation. Both processes generate an impermeable and rigid carapace allowing
overpressurisation of the inner parts of the lava dome by the rapid input of
vesiculated magma batches. The relative thickness of the cristobalite-rich
carapace is an inverse function of the external lava dome surface area. Explosive
activity is thus more likely to occur at the onset of lava dome extrusion, in
agreement with observations, as the likelihood of superficial lava dome
explosions depends inversely on lava dome volume. This new result is of interest
for the whole volcanological community and for risk management.
PMID- 26420070
TI - Bifidobacterium breve prevents necrotising enterocolitis by suppressing
inflammatory responses in a preterm rat model.
AB - Necrotising enterocolitis (NEC) is associated with inflammatory responses and
barrier dysfunction in the gut. In this study, we investigated the effect of
Bifidobacterium breve M-16V on factors related to NEC development using an
experimental rat model. Caesarean-sectioned rats were given formula milk with or
without B. breve M-16V by oral gavage thrice daily, and experimental NEC was
induced by exposing the rats to hypoxic conditions. Naturally delivered rats that
were reared by their mother were used as healthy controls. The pathological score
of NEC and the expression of molecules related to inflammatory responses and the
barrier function were assessed in the ileum. B. breve M-16V reduced the
pathological scores of NEC and resulted in some improvement in survivability. B.
breve M-16V suppressed the increased expression of molecules related to
inflammation and barrier function that resulted from NEC induction. B. breve M
16V normalised Toll-like receptor (TRL)4 expression and enhanced TLR2 expression.
Our data suggest that B. breve M-16V prevents NEC development by modulating TLR
expressions and suppressing inflammatory responses in a rat model.
PMID- 26420071
TI - HIV transmission law in the age of treatment-as-prevention.
AB - Evidence that treating people with HIV early in infection prevents transmission
to sexual partners has reframed HIV prevention paradigms. The resulting emphasis
on HIV testing as part of prevention strategies has rekindled the debate as to
whether laws that criminalise HIV transmission are counterproductive to the human
rights-based public health response. It also raises normative questions about
what constitutes 'safe(r) sex' if a person with HIV has undetectable viral load,
which has significant implications for sexual practice and health promotion. This
paper discusses a recent high-profile Australian case where HIV transmission or
exposure has been prosecuted, and considers how the interpretation of law in
these instances impacts on HIV prevention paradigms. In addition, we consider the
implications of an evolving medical understanding of HIV transmission, and
particularly the ability to determine infectiousness through viral load tests,
for laws that relate to HIV exposure (as distinct from transmission) offences. We
conclude that defensible laws must relate to appreciable risk. Given the evidence
that the transmissibility of HIV is reduced to negligible level where viral load
is suppressed, this needs to be recognised in the framing, implementation and
enforcement of the law. In addition, normative concepts of 'safe(r) sex' need to
be expanded to include sex that is 'protected' by means of the positive person
being virally suppressed. In jurisdictions where use of a condom has previously
mitigated the duty of the person with HIV to disclose to a partner, this might
logically also apply to sex that is 'protected' by undetectable viral load.
PMID- 26420072
TI - Survey of Japanese mothers of daughters eligible for human papillomavirus
vaccination on attitudes about media reports of adverse events and the suspension
of governmental recommendation for vaccination.
AB - AIM: Following media reports of adverse medical events surrounding human
papillomavirus (HPV) vaccination and the suspension of Japanese governmental
recommendation, most adolescents have refrained from receiving the vaccine. This
represents a national critical event, because the incidence of cervical cancer in
Japan continues to increase. METHODS: We conducted an Internet survey to
investigate why Japanese adolescent girls decline, continue or discontinue their
HPV vaccination, how their mothers influence their decision, and the mothers'
feelings about future HPV vaccination for their daughters. One thousand mothers
with daughters 10-18 years of age were recruited for our questionnaire. RESULTS:
Our results suggest that acceptance of the HPV vaccine was determined
predominantly by the mother's perceptions of risk versus benefits, rather than
the daughter's wishes. The mothers' knowledge of the benefits of the prophylactic
HPV vaccine and their attitude toward cervical cancer screening influenced their
decision whether to allow their daughter to receive future vaccinations. The
tenor of survey responses of those mothers who were anti-vaccine changed
significantly to the positive in response to a proposed scenario where the
governmental recommendation for the HPV vaccine was reinstated, whereas a
hypothetical educational intervention sheet did not significantly change their
attitude. CONCLUSIONS: Promotion of the HPV vaccine through comprehensive
education for both mothers and daughters, not only on the vaccine itself, but
also about cervical cancer and screening, is required for any successful program
to prevent cervical cancer.
PMID- 26420074
TI - Detection and Occurrence of Indicator Organisms and Pathogens.
AB - This review summarizes the literature pertaining to the occurrence and detection
of indicator organisms and pathogens published during 2014. It is organized into
the following sections: i) detection and quantification of fecal indicators and
waterborne pathogens, ii) microbial source tracking (MST) using genotypic and
phenotypic methods, iii) antibiotic resistant bacteria (ARB), iv) live vs. dead
cell differentiation methods, and v) next generation sequencing (NGS).
PMID- 26420073
TI - Detection, Occurrence and Fate of Emerging Contaminants in Agricultural
Environments.
AB - A total of 43 papers published in 2014 were reviewed ranging from detailed
descriptions of analytical methods, to fate and occurrence studies, to measuring
and predicting biological effects for a wide variety of emerging contaminants
likely to occur in agricultural environments. New methods and studies on
veterinary pharmaceuticals, natural and synthetics steroids, and antibiotic
resistance genes in agricultural environments continue to expand our knowledge
base on the occurrence and potential impacts of these compounds. This review is
divided into the following sections: Introduction, Analytical Methods, Occurrence
and Fate, Antibiotic Resistance Genes, and Risk Assessment.
PMID- 26420076
TI - Physico-Chemical Processes.
AB - This review is on the research literature published in 2014 related to the
physico-chemical processes for water and wastewater treatment. The review is
divided into six sections, including coagulation/flocculation, filtration,
sedimentation, oxidation, flotation, sorption process.
PMID- 26420075
TI - Wastewater Collection Systems.
AB - This chapter presents a review of the literature published in 2014 on topics
relating to wastewater collection systems. It presents advances in noteworthy
research and industry experiences selected from major literature sources. This
review is divided into the following sections: sewer system planning; sewer
condition assessment/rehabilitation; pump stations and system design; operation
and maintenance; and regulatory issues/ integrated planning.
PMID- 26420078
TI - Biological Fixed Film.
AB - The review includes literatures published in the year of 2014 regarding the uses
of biofilm and bioreactor to treat wastewater. Topics considered are: biofilm
formation and factors that impact biofilm formation; extracellular polymeric
substance from biofilms; biofilm consortia and quorum sensing; biofilm reactors
and biofilm in bioelectrochemical systems.
PMID- 26420077
TI - Activated Sludge and other Aerobic Suspended Culture Processes.
AB - This is a literature review for the year 2014 and contains information
specifically associated with suspended growth processes including activated
sludge and sequencing batch reactors. This review is a subsection of the
treatment systems section of the annual literature review. The review encompasses
modeling and kinetics, nutrient removal, system design and operation. Compared to
past reviews, many topics show increase in activity in 2014. These include,
nitrogen and phosphorus control, fate and effect of xenobiotics, industrial
wastes treatment, and some new method for the determination of activated sludge.
These topics are referred to the degradation of constituents in activated sludge.
Other sections include population dynamics, process microbiology of activated
sludge, modeling and kinetics. Many of the subsections in the industrial wastes:
converting sewage sludge into fuel gases, thermos-alkali hydrolysis of Waste
Activated Sludge (WAS), sludge used as H2 S adsorbents were also mentioned in
this review.
PMID- 26420079
TI - Membrane Processes.
AB - This review, for literature published in 2014, contains information related to
membrane processes for municipal and industrial applications. This review is a
subsection of the Treatment Systems section of the annual Water Environment
Federation literature review and covers the following topics: pretreatment,
membrane bioreactor (MBR) configuration, design, nutrient removal, operation,
industrial treatment, fixed film and anaerobic membrane systems, reuse,
microconstituents removal, membrane technology advances, membrane fouling, and
modeling. Other sub-sections of the Treatment Systems section that might relate
to this literature review include: Biological Fixed-Film Systems, Activated
Sludge and Other Aerobic Suspended Culture Processes, Anaerobic Processes, Water
Reclamation and Reuse. The following sections might also have related information
on membrane processes: Industrial Wastes, Hazardous Wastes, and Fate and Effects
of Pollutants.
PMID- 26420080
TI - Anaerobic Process.
AB - A review of the literature published in 2014 on the focus of Anaerobic Process.
It is divided into the following sections. *Pretreatment *Organic waste *multiple
stage co-digestion *Process Methodology and Technology.
PMID- 26420082
TI - Disinfection Processes.
AB - A review of the literature published in 2014 on topics relating to disinfection
processes is presented. This review is divided into the following sections:
disinfection methods, disinfection byproducts, and microbiology and microbial
communities.
PMID- 26420081
TI - Wetlands for Wastewater Treatment.
AB - This paper provides a review of the treatment technologies, which utilize natural
processes or passive components in wastewater treatment. In particular, this
paper primarily focuses on wetland systems and their applications in wastewater
treatment (as an advanced treatment unit or decentralized system), nutrient and
pollutant removal (single and multiple pollutants, and metals), and emerging
pollutant removal (pharmaceuticals). A summary of studies involving the plant
(vegetation) effects, wetland design and modeling, hybrid and innovative systems,
storm water treatment and pathogen removal is also included.
PMID- 26420083
TI - Biosolids and Sludge Management.
AB - This review section covers journal articles and conference papers related to
biosolids and sludge management that were published in 2014. The literature
review has been divided into the following sections: * Biosolids regulations and
management issues; * ;Biosolids characteristics, quality and measurement
including microconstituents and pathogens; * Sludge treatment technologies
including pretreatment and sludge minimization, conditioning and dewatering,
digestion, composting and innovative technologies; * Disposal and reuse including
combustion/ incineration, land application and non- agricultural use; * Odor and
air emissions; and * Energy issues.
PMID- 26420084
TI - Gaseous Emissions from Wastewater Facilities.
AB - A review of the literature published in 2014 on topics relating to gaseous
emissions from wastewater facilities is presented. This review is divided into
the following sections: odorant emissions from wastewater treatment plants
(WWTPs); greenhouse gas (GHG) emissions from WWTPs; gaseous emissions from
wastewater collection systems; physiochemical odor/emissions control methods;
biological odor/emissions control methods; odor characterization/monitoring; and
odor impacts/risk assessments.
PMID- 26420085
TI - Modeling, Instrumentation, Automation, and Optimization of Water Resource
Recovery Facilities.
AB - A review of the literature published in 2014 on topics relating to water resource
recovery facilities (WRRF) in the areas of modeling, instrumentation, automation
and optimization of wastewater treatment is presented. Note that WEF has adopted
'WRRF' replacing such previous terms as publicly owned treatment works,
wastewater treatment plant (WWTP), and other terms and officially instituted this
change in its publications beginning in 2012. It is anticipated the replaced
terms will remain in use by other publications and authors for some time. This
review will strive to maintain consistency with this change but also avoid
confusion where possible.
PMID- 26420086
TI - Distributed Treatment Systems.
AB - This section presents a review of the literature published in 2014 on topics
relating to distributed treatment systems. This review is divided into the
following sections with multiple subsections under each: constituent removal;
treatment technologies; and planning and treatment system management.
PMID- 26420087
TI - Sustainability.
AB - This review on Sustainability covers selected 2014 publications on the focus of
the following sections: * Sustainable water and wastewater utilities *
Sustainable water resources management * Stormwater and green infrastructure *
Sustainability in wastewater treatment * Life cycle assessment (LCA) applications
* Sustainability and energy in wastewater industry, * Sustainability and asset
management.
PMID- 26420088
TI - Agricultural Waste.
AB - The management and disposal of agricultural waste are drawn more and more
attention because of the increasing yields and negative effects on the
environment. However, proper treatments such as converting abundant biomass
wastes into biogas through anaerobic digestion technology, can not only avoid the
negative impacts, but also convert waste into available resources. This review
summarizes the studies of nearly two hundred scholars from the following four
aspects: the characterization, reuse, treatment, and management of agricultural
waste.
PMID- 26420089
TI - Automotive Wastes.
AB - A review of the literature from 2014 related to automotive wastes is presented.
Topics include solid wastes from autobodies and tires as well as vehicle
emissions to soil and air as a result of the use of conventional and alternative
fuels. Potential toxicological and health risks related to automotive wastes are
also discussed.
PMID- 26420090
TI - Chemical Waste and Allied Products.
AB - This review of literature published in 2014 focuses on waste related to chemical
and allied products. The topics cover the waste management practices, hospital
waste, pesticide waste, chemical wastewater, pesticide wastewater and
pharmaceutical wastewater. The other topics include aerobic treatment, anaerobic
treatment, sorption and ozonation.
PMID- 26420091
TI - Food-Processing Wastes.
AB - Literature published in 2014 and early 2015 related to food processing wastes
treatment for industrial applications are reviewed. This review is a subsection
of the Treatment Systems section of the annual Water Environment Federation
literature review and covers the following food processing industries and
applications: general, meat and poultry, fruits and vegetables, dairy and
beverage, and miscellaneous treatment of food wastes.
PMID- 26420092
TI - Mine Drainage and Oil Sand Water.
AB - Mine drainage from the mining of mineral resources (coal, metals, oil sand, or
industrial minerals) remains as a persistent environmental problem. This review
summarizes the scientific literature published in 2014 on the technical issues
related to mine drainage or mine water in active and abandoned coal/hard rock
mining sites or waste spoil piles. Also included in this review is the water from
oil sand operations. This review is divided into the four sections: 1) mine
drainage characterization, 2) prediction and environmental impact, 3) treatment
technologies, 4) oil sand water. Many papers presented in this review address
more than one aspect and different sections should not be regarded as being
mutuallyexclusive or all-inclusive.
PMID- 26420093
TI - Textiles.
AB - A review of the literature published in 2014 on topics relating to the treatment
alternatives for wastewater from the textile industries is presented. This review
is divided into the following sections: a brief introduction on the
implementation of the Best Available Techniques into textile industry, a review
of the more promising treatment technologies distinguished into physico-chemical,
biological and combined processes.
PMID- 26420094
TI - Bioenergy from Biofuel Residues and Wastes.
AB - This review includes works published in the general scientific literature during
2014 on the production of bioenergy and biofuel from waste residues generated
during bioethanol and biodiesel production with a brief overview of current and
emerging feedstocks. Anothersection of this review summarizes literature on
culturing algae for biofuels including bioreactors and open pond cultivation
systems with the utilization of inorganic and organic sources of nutrients. New
methods applicable to the mass culture of algae are highlighted. Algal cell
harvesting and oil extraction techniques tested and developed for algae are also
discussed.
PMID- 26420095
TI - Hazardous Waste Treatment Technologies.
AB - The article reviews the scientific literature published in 2014 on physical,
chemical, and biological treatment of hazardous contaminants and environmental
bioremediation.
PMID- 26420096
TI - Radioactive Wastes.
AB - Papers reviewed herein present a general overview of radioactive waste activities
around the world in 2014. These include safety assessments, decommission and
decontamination of nuclear facilities, fusion facilities, transportation and
management solutions for the final disposal of low and high level radioactive
wastes (LLW and HLW), interim storage and final disposal options for spent fuel
(SF), and tritiated wastes, with a focus on environmental impacts due to the
mobility of radionuclides in water, soil and ecosystem alongwith other progress
made in the management of radioactive wastes.
PMID- 26420097
TI - Mixing and Transport.
AB - This section covers research published during the calendar year 2014 on mixing
and transport processes. The review covers mixing of anaerobic digesters, mixing
of heat transfer, and environmental fate and transport.
PMID- 26420098
TI - Stream, Lake, and Reservoir Management.
AB - This review on stream, lake, and reservoir management covers selected 2014
publications on the focus of the following sections: * Biota * Climate effect *
Models * Remediation and restoration * Reservoir operations * Stream, Lake, and
Reservoir Management * Water quality.
PMID- 26420099
TI - Contaminated Aquatic Sediments.
AB - A review of the literature published in 2014 relating to the assessment,
evaluation and remediation of contaminated aquatic sediments is presented. The
review is divided into the following sections: policy and guidance, methodology,
distribution, fate and transport, bioavailability, bioaccumulation, risk,
toxicity and remediation.
PMID- 26420100
TI - Nonpoint Source Pollution.
AB - The article presents a comprehensive review of research advancing in 2014 on
nonpoint source pollution (NPS). The topics presented relate to nonpoint source
pollution (NPS) within agricultural and urban areas. NPS pollution from
agricultural areas is the main focus in this review. Management of NPS in
agricultural, urban and rural areas is presented. Modeling of NPS pollution in
different watersheds with various modeling tools is reviewed.
PMID- 26420101
TI - Fate of Environmental Pollutants.
AB - This annual review covers the literature published in 2014 on topics related to
the occurrence and fate of emerging environmental pollutants in wastewater. Due
to the vast amount of literature published on this topic, I have discussed only a
fraction of the quality research publications, up to maximum 15 relevant articles
per section, due to limitation of space. The abstract search was carried out
using Web of Science, and the abstracts were selected based on their relevance.
In few cases, full-text articles were referred to better understand new findings.
This review is divided into the following sections: biological agents,
disinfection by-products (DBPs), halogenated compounds, pharmaceuticals and
personal care products (PPCPs), and other emerging contaminants.
PMID- 26420102
TI - Substratum-Associated Microbiota.
AB - This review of literature on substratumassociated microbiota from 2014 highlights
topics on benthic algae and bacteria from a range of aquatic environments, but
focuses on freshwater habitats. Advances in pollution and toxin detection,
assessment methods, and applications of new technologies are highlighted as are
updates in taxonomy and systematics. Aspects of general ecology, water quality,
nutrient cycling, trophic interactions, land use changes, biofuels, biofouling,
and environmental challenges such as climate change, pollutants, tar sands and
fracking, oil spills and nuisance blooms are presented.
PMID- 26420103
TI - Effects of Pollution on Freshwater Organisms.
AB - This review includes works published in the general scientific literature during
2014 on the effects of anthropogenic pollutants on freshwater organisms. It
begins with two broad sections: research reviews and broad field studies and
surveys. This is followed by reviews of research categorized in sections to
reflect the pollutant class. These sections include wastewater, stormwater and
non-point source pollution, nutrients, sediment cap materials and suspended
clays, botanical extracts, surfactants, metals, persistent organic pollutants,
pharmaceuticals, endocrine disruptors, pesticides, petroleum hydrocarbons and
polycyclic aromatic hydrocarbons (PAHs), ionic liquids, and nanomaterials. The
final section includes works describing innovations in the field of freshwater
pollution research.
PMID- 26420104
TI - Effects of Pollution on Marine Organisms.
AB - This review covers selected 2014 articles on the biological effects of pollutants
and human physical disturbances on marine and estuarine plants, animals,
ecosystems and habitats. The review, based largely on journal articles, covers
field and laboratory measurement activities (bioaccumulation of contaminants,
field assessment surveys, toxicity testing and biomarkers) as well as pollution
issues of current interest including endocrine disrupters, emerging contaminants,
wastewater discharges, dredging and disposal, etc. Special emphasis is placed on
effects of oil spills and marine debris due in part to the 2010 Deepwater Horizon
oil blowout in the Gulf of Mexico and the 2011 Japanese tsunami. Several topical
areas reviewed in the past (ballast water and ocean acidification) were dropped
this year. The focus of this review is on effects, not pollutant fate and
transport. There is considerable overlap across subject areas (e.g.some
bioaccumulation papers may be cited in other topical categories). Please use
keyword searching of the text to locate related but distributed papers. Use this
review only as a guide and please consult the original papers before citing them.
PMID- 26420105
TI - Health Effects Associated with Wastewater Treatment, Reuse, and Disposal.
AB - A review of the literature published in 2014 on topics relating to public and
environmental health risks associated with wastewater treatment, reuse, and
disposal is presented. This review is divided into the following sections:
wastewater management, microbial hazards, chemical hazards, wastewater reuse,
wastewater treatment plants, wastewater disposal, and sludge and biosolids.
PMID- 26420106
TI - Emerging Pollutants - Part I: Occurrence, Fate and Transport.
AB - Part I: Occurrence, Fate, and Transport (this review) is a sequel of Emerging
Pollutants. This review compiles research in 2014 for investigating emerging
pollutants in wastewater and environmental sources of emerging pollutants. It
investigates the occurrence, fate, transport of emerging pollutants in the
environment. This review further discusses the monitoring approaches, modeling,
and toxicological impacts of these compounds that are relevant to wastewater.
PMID- 26420107
TI - Emerging Pollutants - Part II: Treatment.
AB - Emerging contaminants are considered as some substances of actual or potential
threat to human health or environment, which include endocrine disruptors,
pharmaceutical, personal care products, nanoparticles, antibiotic resistance
genes and chemicals used in packaging products, etc. The disposal and treatment
of emerging contaminants has become a key problem in the field of water pollution
control. The purpose of this review is to summarize published researches on
emerging pollutants treatment in 2014.
PMID- 26420108
TI - Thermal Effects.
AB - This review focuses on the research literatures published in 2014 relating to
topics of thermal effects in water pollution control. This review is divided into
the following sections: anaerobic wastewater and sludge treatment, biological
nitrogen and phosphorus removal, membrane biological treatment, sewage sludge
pyrolysis, natural treatment, resource recovery, electrolysis, oxidation and
adsorption treatment.
PMID- 26420109
TI - Economics.
AB - A review of literature during calendar year 2014 focused on environmental
policies and sustainable development, and economic policies. This review is
divided into these sections: sustainable development, irrigation, ecosystems and
water management, climate change and disaster risk management, economic growth,
water supply policies, water consumption, water price regulation, and water price
valuation.
PMID- 26420110
TI - Analytical Methods for Pesticide Residues in the Water Environment.
AB - A review of literature published in 2014 focusing on analytical methods for
pesticides in the water environment is presented here. The review includes
publications on extraction methods and on analytical methods such as biochemical
assays and immunoassays, electrochemical methods, chromatographic or mass
spectrometric techniques, spectrophotometric techniques, fluorescence, and
chemiluminescence techniques.
PMID- 26420111
TI - [Comprehensive managements and focus on both prevention and therapy are essential
to improve the outcome of patients with glucose metabolism abnormalities and
atherosclerotic diseases].
PMID- 26420112
TI - [Biomarkers and individualized precise treatment of cardiovascular diseases].
PMID- 26420113
TI - [Role of bioactive small molecules in the progression of vascular calcification].
PMID- 26420114
TI - [Diastolic and therapeutic value of biomarkers in children with postural
tachycardia syndrome].
PMID- 26420115
TI - [Research progress on the association between Corin-natriuretic peptides system
and cardiovascular diseases].
PMID- 26420116
TI - [Update on the relationship between C-type natriuretic peptide and cardiovascular
disease].
PMID- 26420117
TI - [Chinese guidelines on the management of glucose metabolism abnormalities and
atherosclerosis cardiovascular diseases].
PMID- 26420118
TI - [Predictive value of baseline plasma midregional fragment of pro-adrenomedullin
level on long-term outcome of postural tachycardia syndrome children treated with
midodrine hydrochloride].
AB - OBJECTIVE: To explore the predictive value of baseline plasma midregional
fragment of pro-adrenomedullin level (MR-proADM) on long-term survival of
postural tachycardia syndrome (POTS) children treated with midodrine
hydrochloride. METHODS: Fifty-three children (male 26, mean age (14.5 +/- 4.5)
years old) with POTS were included in this study, and all of them were diagnosed
as POTS in our department from December 2007 to January 2010. Fifty-three
children with POTS were divided into two groups according to the baseline plasma
content of MR-proADM. Group I consisted of 35 POTS children with plasma content
of MR-proADM > 61.5 ng/L, and the group II consisted of 18 POTS children with
plasma content of MR-proADM <= 61.5 ng/L. The mean follow-up time was (67 +/- 7)
months. The orthostatic intolerance symptom score and the symptom free survival
were compared between the 2 groups. RESULTS: At the 60 months follow-up, the
symptom score of children in group I was significantly lower than that in group
II (chi(2) = 4.985, P < 0.05). At 72 months follow up, the symptom score was
similar between the 2 groups (chi(2) = 0.004, P > 0.05) while the symptom free
survival of group I was significantly higher than that in group II (chi(2) =
4.566, P < 0.05). CONCLUSION: The baseline plasma MR-proADM level is value in
predicting the long-term survival of POTS children treated with midodrine
hydrochloride.
PMID- 26420119
TI - [Plasma amino-terminal pro-brain natriuretic peptide level and affecting factors
in a community-based healthy Chinese population].
AB - OBJECTIVE: To investigate the plasma level of amino-terminal pro-brain
natriuretic peptide (NT-proBNP) and related influencing factors in a community
based healthy population in Beijing area. METHODS: We measured plasma NT-proBNP
level by fluoroimmunoassay between March 2012 and July 2012 from 1 034 healthy
subjects (including 486 men and 548 women). Empiric method was used to determine
the reference value and influencing factors were analyzed. RESULTS: Age and
gender are important factors affecting the level of NT-proBNP in healthy
subjects. NT-proBNP plasma level is significantly higher in women than in men
within each age strata below 75 years old, i.e. < 45, 45-54, 55-64 and 65-74
years old (P = 0.005, 0.001, 0.001, 0.011 respectively), but NT-proBNP plasma
level is similar between male and female older than 75 years (P = 0.504). NT
proBNP level also increases with age irrespective of gender. Body mass index
(BMI) is another independent influencing factor of NT-proBNP (P < 0.001), while
estimated glomerular filtration rate is not influencing factor. The reference
range of NT-proBNP is < 133 ng/L for men and < 289 ng/L for women aged < 55 years
old, < 185 ng/L for men and < 333 ng/L for women aged between 55 and 64 years
old, and < 465 ng/L for men and < 378 ng/L for women aged >= 75 years old.
CONCLUSION: The major influencing factors of NT-proBNP level in the healthy
population are age, gender and BMI. It essential to establish normal reference
range of NT-proBNP according to these factors for Chinese population.
PMID- 26420120
TI - [Potential role of microRNA-181b on atherosclerosis].
AB - OBJECTIVE: To observe the serum expression of miR-181b in atherosclerotic
patients and the in vitro effects of miR-181b on vascular smooth muscle cell
growth and migration. METHODS: Fifty patients (mean age: (78.1 +/- 8.9) years
old) with carotid ultrasound examination evidenced atherosclerotic plaque were
enrolled as the atherosclerosis group and 50 healthy (mean age: (72.5 +/- 10.7)
years old) subjects serve as control group. Stem-loop real time RT-PCR was used
to detect the serum expression of miR-181b. Importin-alpha3 was predicted to be a
direct target of miR-181b by Targetscan and Pictar. Western-blot was employed to
detect the in vitro effects of miR-181b on the expression of Importin-alpha3 in
endothelial cells. Luciferase reporter assay was employed to testify the
prediction. The effects of miR-181b on vascular smooth muscle cell growth,
migration abilities were respectively examined by CCK8 assay and Matrigel
migration assay. RESULTS: Compared with healthy controls, serum expression of miR
181b was significantly down-regulated in patients with atherosclerosis (31.69 +/-
0.96 vs. 82.28 +/- 5.95, P < 0.05); Importin-alpha3 was predicted and proved to
be a direct target of miR-181b by Western-blot and luciferase reporter assay. The
proliferation and migration of vascular smooth muscle cell were significantly
downregulated by forced expression of miR-181b (1.57 +/- 0.18 vs. 2.66 +/- 0.16,
P < 0.05; 8.7 +/- 1.1 vs. 21.4 +/- 2.3, P < 0.05), while these effects could be
abolished by inhibition of miR-181b (2.88 +/- 0.09 vs. 2.04 +/- 0.11, P < 0.05;
15.2 +/- 1.5 vs. 8.4 +/- 1.3, P < 0.05). CONCLUSION: The serum miR-181b level was
significantly reduced in patients with atherosclerosis. miR-181b may function as
an atherosclerosis suppressor by interupting the NF-kappaB pathway in endothelial
cells and inhibiting the proliferation and migration of vascular smooth muscle
cells.
PMID- 26420121
TI - [TPM1 gene mutation is associated with dilated cardiomyopathy in Kazaks in
Xinjiang].
AB - OBJECTIVE: Detect the relationship between TPM1 gene mutations and dilated
cardiomyopathy (DCM) of Kazaks and Hans in Xinjiang. METHODS: TPM1 gene was
screened from 31 family members in a Kazak family with familiar DCM (FDCM), 100
patients with idiopathic DCM (IDCM, 50 Kazaks and 50 Hans), and in 100 healthy
controls (50 Kazaks and 50 Hans). All the samples were the inpatients or
outpatients of First Affiliated Hospital of Xinjiang University from 2012 to
2014. PCR was used to amplify 9 exons and nearby introns of the TPM1 gene. The
amplified products were sequenced and compared with the standard sequence with
CHROMAS software and BLAST software in Pubmed to identify mutation sites. The
relationship between TPM1 gene mutations in the Kazak IDCM and healthy
volunteers, between Han and Kazak IDCM and healthy volunteers was analyzed.
Tropomyosin was qualitatively and quantitatively detected by ELISA in all
subjects. RESULTS: A novel variant (c.524 G > T) was identified in two FDCM
patients at exon 3, this mutation caused an amino acid substitution, Gln111His.
The FDCM, IDCM from Kazak and Han, healthy volunteers from Kazak and Han were
founded a rs1071646 (c.644C > A, Ala151Ala). There was a significant difference
in the genotype distribution (chi(2) = 13.36, P = 0.001) and allele frequency
(chi(2) = 10.25, P = 0.001) between Kazaks with IDCM and Kazak controls of
rs1071646, while these parameters were similar between Han IDCM patients and Han
controls (all P > 0.05). The tropomyosin content of Kazak and Han IDCM patients
were significantly lower than Kazak and Han controls ((1 764.2 +/- 350.9) ng/L
vs. (2 369.7 +/- 345.9) ng/L, P = 0.001). CONCLUSION: TPM1 gene of rs1071646
polymorphism is a possible independent risk factor for IDCM in Kazaks but not Han
Chinese.
PMID- 26420122
TI - [Impact of fenestration on early outcome in patients undergoing modified Fontan
operation].
AB - OBJECTIVE: To compare the impact of fenestration on early outcome in patients
undergoing modified Fontan operation. METHODS: Data from 90 consecutive patients
underwent modified Fontan operation from November 2008 to June 2013 were
retrospectively analyzed. Patients were divided into fenestrated group (49
patients) and non-fenestrated group (41 patients) and early outcome post
operation was compared between the two groups. RESULTS: Anatomy, age, gender,
body weight and disease classifications were similar between the two groups (all
P > 0.05). Postoperative central venous pressure was (11.4 +/- 4.1) mmHg (1 mmHg
= 0.133 kPa) in fenestrated group and (12.1 +/- 3.8) mmHg in non-fenestrated
group (P = 0.894). The duration of chest tube drainage was (11.1 +/- 9.2) day in
fenestrated group and (15.0 +/- 10.7) day in non-fenestrated group (P = 0.160).
Volume of pleural drainage was 772.0 (411.5-1 971.5) ml in fenestrated group and
1 259.0 (571.0-2 647.5) ml in non-fenestrated group (P = 0.214). Duration of ICU
stay was 24.0 (18.0-40.0) day in fenestrated group and 24.0 (19.0-36.0) day in
non-fenestrated group (P = 0.751). The time of respirator use was 9.0 (6.0-15.0)
hours in fenestrated group and 8.0 (6.0-16.0) hours in non-fenestrated group (P =
0.951). Duration of hospital stay was significantly longer in fenestrated group
than in non-fenestrated group ((32.7 +/- 23.0) day vs. (27.8 +/- 12.6) day, P =
0.025). One patient (2.0%) died of low cardiac output syndrome in fenestrated
group and 1 patient (2.4%) experienced hydropericardium in non-fenestrated group.
The incidence rate of complications (P = 0.898) and mortality (P = 1.000) were
similar between the two groups. CONCLUSION: Early outcome is similar for patients
undergoing the modified Fontan operation with or without fenestration.
PMID- 26420123
TI - [Impact of mesenchymal stem cells transplantation on myocardial myocardin-related
transcription factor-A and bcl-2 expression in rats with experimental myocardial
infarction].
AB - OBJECTIVE: To observe the impact of mesenchymal stem cells (BMSCs)
transplantation on myocardial myocardin-related transcription factor-A (MRTF-A)
and bcl-2 expression in rats with experimental myocardial infarction (MI).
METHODS: Thirty rats were randomly divided into sham, MI and MI + BMSCs (1 *
10(6) injected into 4 infarct points immediately post coronary artery ligation)
groups (n = 10 each).One week later, TUNEL was used to detect cardiomyocyte
apoptosis, the myocardial expression of MRTF-A and bcl-2 was detected by laser
scanning confocal microscope and Western blot. In vitro plasmid of MRTF-A and co
transfection with plasmids of MRTF-A and bcl-2 or mutated bcl-2 transfection into
cardiomyocyte was applied to evaluate the relationship between MRTF-A and bcl-2.
RESULTS: The number of apoptotic cardiomyocytes in the sham group, MI group and
MI + BMSCs group were (4.05 +/- 1.56)%, (62.38 +/- 8.41)% and (22.36 +/- 6.17)%,
respectively (P < 0.05). The protein expression of MRTF-A and bcl-2 in the MI
group were significantly lower than those in sham group, while significantly
upregulated in MI + BMSCs group (P < 0.05 vs. MI). In cultured neonatal rat
cardiomyocyte, the expression of bcl-2 protein was significantly upregulated
after transfection with MRTF-A plasmid, and bcl-2-luciferase activity
significantly increased after co-transfection with plasmids of MRTF-A and bcl-2
luciferase, however, the positive regulatory effect of MRTF-A was abolished after
transfection with mutated bcl-2. CONCLUSION: Mesenchymal stem cells
transplantation can effectively reduce cardiomyocyte apoptosis in this rat MI
model, and upregulate the expression of MRTF-A. Consequent up-regulated bcl-2
expression might be involved in the beneficial effects of BMSCs transplantation
in this model.
PMID- 26420124
TI - [Impact and related mechanism of exogenous receptor activity modifying protein 1
on calcitonin gene-related peptide modified bone marrow mesenchymal stem cells on
the migration of vascular smooth muscle cells in vitro].
AB - OBJECTIVE: To investigate the impact of calcitonin gene-related peptide (CGRP)
modified bone marrow mesenchymal stem cell (MSC) on the migration of vascular
smooth muscle cell (VSMC) and related mechanisms. METHODS: The MSC and VSMC were
isolated from rats and cultured, CGRP was transfected to MSC with the high
expression lentivirus vector, VSMC was transfected with high expression
lentivirus vector of receptor activity modifying protein 1 (RAMP1) and the
silence expression lentivirus vector of RAMP1. Then MSC was co-cultured with
VSMC. Experimental groups were as follows: (1) Ang II group (MSC + VSMC + Ang
II); (2) MSC(CGRP+) group (MSC(CGRP+) + VSMC + Ang II); (3) MSC(CGRP+) RAMP1(-)
group (MSC(CGRP+) + VSMC(RAMP1-) + Ang II); (4) MSC(CGRP+) RAMP1(+) group
(MSC(CGRP+) + VSMC(RAMP1+) + Ang II); (5) RAMP1(+) group (MSC + VSMC(RAMP1+) +
Ang II). Transwell assay was applied to detect the migration of smooth muscle
cells, Western blot was applied to detect the protein expression of cells in
various groups. RESULTS: VSMC migration number was significantly lower in
MSC(CGRP+) group compared with Ang II group (50.8 +/- 2.6 vs. 71.4 +/- 2.3, P <
0.05), but higher than in MSC(CGRP+) RAMP1(+) group (50.8 +/- 2.6 vs. 30.4 +/-
3.0, P < 0.05). When RAMP1 expression reduced in VSMC, compared with MSC(CGRP+)
RAMP1(+) group, VSMC migration increased in the MSC(CGRP+) RAMP1(-) group
compared to MSC(CGRP+)RAMP1(+) (69.0 +/- 5.6 vs. 30.4 +/- 3.0, P < 0.05) and was
similar to Ang II group (69.0 +/- 5.6 vs. 71.4 +/- 2.3, P > 0.05) and RAMP1(+)
group (71.6 +/- 3.4). According to the result of Western blot, P-P65 protein
expression in MSC(CGRP+) group was lower than that in Ang II group (0.475 +/-
0.022 vs.0.642 +/- 0.035, P < 0.05). P-P65 protein expression in MSC(CGRP+)RAMP1(
) group was higher than that in MSC(CGRP+) RAMP1(+) group (0.670 +/- 0.030 vs.
0.373 +/- 0.041, P < 0.05), and there was no difference between MSC(CGRP+)RAMP1(
) group and Ang II group (P > 0.05). P-P65 protein expression was similar between
RAMP1(+) group (0.643 +/- 0.039) and Ang II group (P > 0.05). CONCLUSIONS: CGRP
inhibits VSMC migration through RAMP1. NF-kappaB and RAMP1 play crucial role in
the inhibiting effects of CGRP on VSMC migration. Thus, RAMP1-CGRP signaling
inhibits VSMC migration through NF-kappaB signal pathways.
PMID- 26420125
TI - [Effects of norepinephrine on proliferation and apoptosis of neonatal cardiac
fibroblasts in rats].
AB - OBJECTIVE: To investigate the effects of different concentrations of
norepinephrine (NE) on proliferation and apoptosis of cultured cardiac
fibroblasts (CFBs) from neonatal mice and to elucidate related mechanisms.
METHODS: CFBs of Sprague-Dawley (SD) rats were isolated and cultured and divided
into normal control group and different concentration of NE intervention groups
(0.1, 1, 10, 50, and 100 umol/L). Water soluble tetrazolium-1 (WST-1) assay was
carried out to detect the viability of CFBs. Morphology of apoptosis cells was
evaluated by fluorescence microscope with terminal deoxynucleotidyl transferase
dUTP nick end labeling (TUNEL) staining. The expressions of collagen I, collagen
III, pro-oncogene c-myc in CFBs were detected by reverse transcription-polymerase
chain reaction (RT-PCR). The phospho-mitogen activated protein kinase (p-p38MAPK)
and caspase3 protein levels were examined by Western blot. RESULTS: Proliferation
was significantly increased in 1 umol/L and 10 umol/L groups compared with the
normal control group (1.05 +/- 0.05 and 1.09 +/- 0.02 vs. 1.00 +/- 0.03, all P <
0.05).CFBs apoptosis was significantly enhanced in 50 umol/L and 100 umol/L
groups ((22.69 +/- 2.18)% and (36.40 +/- 6.80)% vs.(4.50 +/- 1.08)%, all P <
0.05). Expression of Collagen I peaked in 10 umol/L group, expression of collagen
III and c-myc increased dose-dependently in proportion to increasing NE
concentrations (all P < 0.05 vs. control group). The expression of p-p38MAPK and
caspase3 was also significantly upregulated in a dose-dependent manner in NE
groups (all P < 0.05 vs. control group). CONCLUSIONS: Low concentration NE
induces CFBs proliferation and high concentration NE promotes CFBs apoptosis.
p38MAPK phosphorylation may be a major mediator of NE-induced effects on CFBs.
PMID- 26420126
TI - [Relationship between central obesity and clustering of cardiovascular risk
factors in adults of Jiangsu province].
AB - OBJECTIVE: To explore the relationship between central obesity and cardiovascular
risk factors and their clustering in adults of Jiangsu province. METHODS: Multi
stratified clustering sampling method was used to sample 8 400 residents aged 18
years and over from 14 diseases surveillance units in Jiangsu province from
October to December 2010. Information was obtained with face-to-face interview,
physical examination and laboratory testing. A total of 8 380 residents finished
the study protocol and their data were analyzed. Central obesity was defined as
waist circumference >= 85 cm in males or >= 80 cm in females. Following complex
weighting of the samples, level and proportion of cardiovascular risk factors in
group with different waist circumference were analyzed. RESULTS: The prevalence
of central obesity among adults in Jiangsu province was 46.2%, the proportion of
males and females was 46.4% and 46.1%, respectively (P > 0.05). The prevalence of
center obesity varied significantly in residents with different age, area,
education and occupation (all P < 0.01). The level of systolic blood pressure,
diastolic blood pressure, fasting blood glucose, total cholesterol, triglyceride,
high density lipoprotein cholesterol and low density lipoprotein cholesterol was
also significantly different in residents with different degree of waist
circumference (all P < 0.01). The prevalence of hypertension, diabetes,
dyslipidemia and clustering of cardiovascular risk factors increased in
proportion to increasing waist circumference (all P < 0.05). Multivariate
logistic regression analysis showed that the risk of hypertension, diabetes,
dyslipidemia and clustering of cardiovascular risk factors was 2.2 (OR = 2.2, 95%
CI: 2.0-2.4) and 4.7 (OR = 4.7, 95% CI: 3.9-5.7); 2.1 (OR = 2.1, 95% CI: 1.7-2.5)
and 3.8 (OR = 3.8, 95% CI: 3.2-4.5); 2.3 (OR = 2.3, 95% CI: 1.8-2.9) and 4.1 (OR
= 4.1, 95% CI: 3.2-5.3); 3.4 (OR = 3.4, 95% CI: 2.9-3.9) and 8.0 (OR = 8.0, 95%
CI: 6.2-10.2) fold higher in residents with mild and severe central obesity than
residents without central obesity. CONCLUSIONS: The extent of central obesity
positively correlates with the prevalence of cardiovascular risk factors and
their clustering in adults of Jiangsu province. Comprehensive interventions on
obesity serve as an important tool to reduce the cardiovascular risk in adult
Jiangshu residents.
PMID- 26420127
TI - [Meta-analysis of clinical trials of folic acid, vitamin B12 and B6
supplementation on plasma homocysteine level and risk of cardiovascular disease].
AB - OBJECTIVE: To evaluate the effects of folic acid, vitamin B(6) and B(12)
supplementation on plasma homocysteine level and risk of cardiovascular disease.
METHODS: The databases, including Embase, Pubmed, Ovid, Biosis, China National
Knowledge Infra-structure (CNKI), Wanfang Data, VIP Database for Chinese
Technical Periodical (VIP), Chinese Biomedical Literature Database (CMB), were
searched to identify random control trials between February 1994 to February 2014
on the effect of folic acid, vitamin B(6) and B(12) supplementation on plasma
homocysteine level and risk of cardiovascular disease. The screening, data
extraction and quality assessment were conducted in accordance with the inclusion
and exclusion criteria by two reviewers independently. The software Review
Manager 5.2 was used. Funnel plots and Egger's regression test were applied to
evaluate the publication bias. RESULTS: Data from 12 studies including 34 481
patients were analyzed using a fixed-effects model. Funnel plot and Egger's test
(P > 0.10) confirmed the absence of publication bias. No statistically
significant heterogeneity was detected on testing after excluding the sources of
heterogeneity (chi-square test, I < 2 < 50%). Baseline homocysteine levels were
similar between the placebo and folic acid, vitamin B(6) and B(12) groups (all P
> 0.05). Mean homocysteine levels were significantly lower with folic acid,
vitamin B(6) and B(12) therapy compared with placebo during follow-up (all P <
0.05). The pooled relative risks with 95% confidence intervals of outcomes for
patients treated with folic acid, vitamin B(6) and B(12) supplementation compared
with placebo were 0.98 (0.93-1.03) for cardiovascular event, 0.97 (0.87-1.07) for
coronary artery disease, 1.00 (0.92-1.08) for myocardial infarction and 0.92
(0.82-1.03) for cardiovascular death. CONCLUSIONS: Folic aicd combined with
vitamin B(6) and B(12) treatment significantly reduced plasma homocysteine level,
but did not affect the risk of cardiovascular disease. Thus, folic acid combined
with vitamin B(6) and B(12) should not be recommended as secondary prevention of
cardiovascular diseases.
PMID- 26420129
TI - [Research progress on etiology and imaging of atrial remodeling].
PMID- 26420128
TI - [Three cases of congenital quadricuspid aortic valve].
PMID- 26420130
TI - [Regulating effects of microRNAs on autophagy and the relationship with
cardiovascular diseases].
PMID- 26420131
TI - A Conserved Structural Motif Mediates Retrograde Trafficking of Shiga Toxin Types
1 and 2.
AB - Shiga toxin-producing Escherichia coli (STEC) produce two types of Shiga toxin
(STx): STx1 and STx2. The toxin A-subunits block protein synthesis, while the B
subunits mediate retrograde trafficking. STEC infections do not have definitive
treatments, and there is growing interest in generating toxin transport
inhibitors for therapy. However, a comprehensive understanding of the mechanisms
of toxin trafficking is essential for drug development. While STx2 is more toxic
in vivo, prior studies focused on STx1 B-subunit (STx1B) trafficking. Here, we
show that, compared with STx1B, trafficking of the B-subunit of STx2 (STx2B) to
the Golgi occurs with slower kinetics. Despite this difference, similar to STx1B,
endosome-to-Golgi transport of STx2B does not involve transit through degradative
late endosomes and is dependent on dynamin II, epsinR, retromer and syntaxin5.
Importantly, additional experiments show that a surface-exposed loop in STx2B
(beta4-beta5 loop) is required for its endosome-to-Golgi trafficking. We
previously demonstrated that residues in the corresponding beta4-beta5 loop of
STx1B are required for interaction with GPP130, the STx1B-specific endosomal
receptor, and for endosome-to-Golgi transport. Overall, STx1B and STx2B share a
common pathway and use a similar structural motif to traffic to the Golgi,
suggesting that the underlying mechanisms of endosomal sorting may be
evolutionarily conserved.
PMID- 26420133
TI - In Silico Prediction of the Effects of Mutations in the Human Mevalonate Kinase
Gene: Towards a Predictive Framework for Mevalonate Kinase Deficiency.
AB - Mevalonate kinase (MVK) catalyses the phosphorylation of mevalonate. Deficiency
of MVK is associated with two rare periodic fever syndromes, mevalonic aciduria
(MA), a severe form and hyper-immunoglobulin-D syndrome (HIDS), a milder form. An
in silico approach was used to analyse the physicochemical and structural effects
of 47 disease-associated variants of MVK. A further 20 variants, which are
present in human genome databases, were also analysed. Variants associated with
MA are clustered into a "hotspot" consisting of residues 8-35 and 234-338 and
tended to result in a prediction of severely reduced protein stability. Four of
the uncharacterised variants, p.H24P, p.G198R, p. R253W, and p.G335S, were likely
to be associated with MA. This method could be used as the basis for initial
predictions of severity when new MVK variants are discovered.
PMID- 26420132
TI - A rare variant association test in family-based designs and non-normal
quantitative traits.
AB - Rare variant studies are now being used to characterize the genetic diversity
between individuals and may help to identify substantial amounts of the genetic
variation of complex diseases and quantitative phenotypes. Family data have been
shown to be powerful to interrogate rare variants. Consequently, several rare
variants association tests have been recently developed for family-based designs,
but typically, these assume the normality of the quantitative phenotypes. In this
paper, we present a family-based test for rare-variants association in the
presence of non-normal quantitative phenotypes. The proposed model relaxes the
normality assumption and does not specify any parametric distribution for the
marginal distribution of the phenotype. The dependence between relatives is
modeled via a Gaussian copula. A score-type test is derived, and several
strategies to approximate its distribution under the null hypothesis are derived
and investigated. The performance of the proposed test is assessed and compared
with existing methods by simulations. The methodology is illustrated with an
association study involving the adiponectin trait from the UK10K project.
PMID- 26420134
TI - Design of Randomized, double-blind, Evaluation in secondary Stroke Prevention
comparing the EfficaCy and safety of the oral Thrombin inhibitor dabigatran
etexilate vs. acetylsalicylic acid in patients with Embolic Stroke of
Undetermined Source (RE-SPECT ESUS).
AB - RATIONALE: Cryptogenic ischemic strokes constitute 20-30% of ischemic strokes,
the majority of which are embolic strokes of undetermined source. The standard
preventive treatment in these patients is usually acetylsalicylic acid. AIM: The
Randomized, double-blind, Evaluation in secondary Stroke Prevention comparing the
EfficaCy and safety of the oral Thrombin inhibitor dabigatran etexilate vs.
acetylsalicylic acid in patients with Embolic Stroke of Undetermined Source (RE
SPECT ESUS) is designed to determine whether the oral thrombin inhibitor
dabigatran, taken within three-months after embolic stroke of undetermined
source, is superior to acetylsalicylic acid for prevention of recurrent stroke
and to characterize the safety of dabigatran in this setting. DESIGN:
Prospective, randomized, double-blind, multicenter trial in approximately 6000
patients and 550 centers with embolic stroke of undetermined source. Subjects are
randomized to dabigatran or acetylsalicylic acid and treated for an expected
minimum of six-months and up to approximately three-years. It is an event-driven
trial aiming for 353 adjudicated primary outcome events. STUDY OUTCOMES: The
primary efficacy outcome is time to first recurrent stroke (ischemic,
hemorrhagic, or unspecified). Key secondary outcomes are time to first ischemic
stroke and time to first occurrence in the composite outcome of nonfatal stroke,
nonfatal myocardial infarction, and cardiovascular death. The primary safety
outcome is major hemorrhage, including symptomatic intracranial hemorrhage.
DISCUSSION: Acetylsalicylic acid is the most common antithrombotic given to
patients with embolic strokes of undetermined source to reduce recurrence risk.
This trial will determine whether anticoagulation with dabigatran is more
effective than acetylsalicylic acid, and acceptably safe.
PMID- 26420142
TI - Species Delimitation's Coming of Age.
PMID- 26420143
TI - Exosomal doxorubicin reduces the cardiac toxicity of doxorubicin.
AB - AIM: To test the efficacy and toxicity of exosomal doxorubicin (exoDOX) compared
with free doxorubicin. MATERIALS & METHODS: The cytotoxic effects of exoDOX were
tested in vitro and in nude mice by measuring the tumor volume. The toxic effects
were evaluated by measuring the bodyweight and through histopathologic analyses.
The biodistribution of DOX was assessed by MS. RESULTS: In vitro and in vivo
studies showed that exosomes did not decrease the efficacy of DOX. Surprisingly,
exoDOX showed no cardiotoxicity as observed in DOX-treated mice and MS studies
confirmed that the accumulation of exoDOX in the heart was reduced by
approximately 40%. CONCLUSION: We demonstrated that exoDOX was less toxic than
DOX through its altered biodistribution.
PMID- 26420144
TI - [Primary aldosteronism: new insights into familial forms].
AB - Primary aldosteronism (PA) is characterized by autonomic aldosterone production,
usually leading to severe hypertension and hypokalaemia. PA is a heterogeneous
condition caused by sporadic adrenal adenoma, bilateral adrenal hyperplasia or
rare familial forms. Familial aldosteronism type 1 is caused by a hybrid gene
that codes for an ACTH-sensitive form of aldosterone synthase. Familial
aldosteronism type 3 was recently recognized as a new form of PA caused by
mutation in KCNJ5. The clinical manifestations vary from life-threatening PA and
pronounced adrenal hyperplasia to milder forms. In addition to germline mutations
in KCNJ5, somatic KCNJ5 mutations are present in about 40% of aldosterone
producing adrenal adenomas. Mutations in three other genes are also regularly
observed. All these mutations cause increased aldosterone synthase activity,
eventually leading to PA. In patients under 20 with PA, familial forms must be
excluded before proceeding to adrenalectomy.
PMID- 26420145
TI - [Ankle sprain during a volleyball game].
AB - A 27-year old woman was admitted to the emergency room after her left ankle
rolled inward during a volleyball game. On physical examination a bony prominence
on the lateral side of the left foot was noticeable, without neurovascular
injury. An X-ray (anterior-posterior view) showed a subtalar dislocation without
associated fractures.
PMID- 26420146
TI - [Group A streptococcal-associated arthritis in children].
AB - Group A streptococcal (GAS) infection can cause septic arthritis (SA), acute
rheumatic fever (ARF) and post-streptococcal reactive arthritis (PSRA).
Differentiating between these three entities can have important consequences for
both therapy and prognosis. SA is diagnosed by means of clinical, biochemical and
microbiological parameters. With respect to ARF and PSRA, evidence of a recent
GAS infection should be established, in combination with several other major or
minor criteria. Currently there is ongoing scientific debate as to whether PSRA
and ARF are two different disease entities or belong to the same spectrum. PSRA
presents earlier after GAS pharyngitis than ARF, is normally less responsive to
NSAIDs, has a longer duration and is often accompanied by skin abnormalities.
However, there are also many similarities. In this report we describe three
children suffering from GAS-associated arthritis and discuss the symptoms,
diagnosis and therapy.
PMID- 26420147
TI - [Referred with the working diagnosis 'pneumothorax: could it be another
diagnosis?].
AB - BACKGROUND: Patients who are referred to an emergency department (ED) often have
a working diagnosis. Hospital physicians may be inclined to accept this diagnosis
and incorrectly link the findings of investigations to it. This may lead to an
incorrect definitive diagnosis and therapy. CASE DESCRIPTION: We present the case
of a 36-year-old female who was referred to the ED with a pneumothorax seen on
chest x-ray. Findings from history-taking, physical examination and a second
chest x-ray taken on the ED were diagnosed as being consistent with pneumothorax
and a chest-drain was inserted. However, further investigation showed that she
had Swyer-James-Mcleod syndrome which could have been treated conservatively.
CONCLUSION: This patient was given a chest drain after the working diagnosis of
pneumothorax was made. Due to the definite diagnosis of Swyer-James-Mcleod the
indication for chest drainage may have been incorrect. If a diagnosis of
pneumothorax is suspected, but diagnostic findings suggest otherwise, further
investigations should be performed before a chest drain is inserted.
PMID- 26420148
TI - [Psychopathology during and after pregnancy].
AB - This article describes two patients with psychosocial problems during and after
pregnancy. The first woman suffers from an obsessive-compulsive disorder and
developed postnatal depression after her first pregnancy. Her second pregnancy
was marked by uncertainty, anxiety and stress. Her caregivers noticed her
problems and referred her to a Psychiatry-Obstetrics-Paediatrics(POP)-team, who
provided her with successful treatment. The second woman had physical symptoms,
which were largely ascribed to antenatal depression and were effectively treated
using antidepressants and cognitive behavioural therapy. Although these patients
experienced different problems in different situations, the impact on the woman,
partner and child(ren) was tremendous in both cases. This article makes clear
that early screening and treatment of symptoms of anxiety and depression are
relevant during and after pregnancy. Vigilance and screening by midwives, family
doctors and gynaecologists help in early recognition and ultimately in earlier
treatment, either medicinal and/or using psychotherapy, which may reduce or even
prevent harmful consequences.
PMID- 26420149
TI - [Unplanned readmissions of frail elderly patients: a retrospective analysis of
admissions in a teaching hospital].
AB - OBJECTIVE: To assess the prevalence and predictors of readmission in patients of
65 years or older. DESIGN: Retrospective data analysis. METHOD: We used a dossier
analysis to identify the number of readmissions and patient characteristics of
all patients aged 65 years or older admitted to the Radboud University Medical
Centre between 29 September 2013 and 4 October 2014. We also used data from the
Dutch hospital safety tool (VMS) screening bundle for frail elderly patients.
Predictors for readmission were investigated using logistic regression analysis.
RESULTS: The readmission rate within 30 days of discharge was 10.9% (95% CI 10.2
11.7) of all admissions of elderly patients. The most common symptom associated
with readmission was dyspnea (24.9%). Diseases with an increased risk for
readmission were: heart failure (OR=2.6; 95% CI 1.9 - 3.7), chronic obstructive
pulmonary disease (OR=2.2; 95% CI 1.5 - 3.2), renal insufficiency (OR=1.8; 95% CI
1.3 - 2.6) and cancer (OR=1.5; 95% CI 1.1 - 2.1). Total burden of disease and
functional limitations accounted jointly for 49% of the variance in readmissions.
Repeated readmissions could be less well predicted (explained variance: 14%); the
use of more than 3 drugs (OR=1.07; 95% CI 1.02 - 1.13) and a low body mass index
(OR=0.94; 95% CI 0.88 - 0.99) were predictors for multiple readmissions.
CONCLUSION: Elderly patients suffering from dyspnea have the highest risk for
readmission. Patients with heart failure, COPD, renal failure, cancer, functional
loss or malnutrition require extra attention on transition from hospital to home
in order to lower the number of unnecessary readmissions.
PMID- 26420162
TI - Sociocultural Factors and Parent-Therapist Agreement on Explanatory Etiologies
for Youth Mental Health Problems.
AB - Sociocultural factors were examined in relationship to parent-therapist agreement
on beliefs about the etiology of mental health problems in a sample of youth
receiving outpatient mental health services (n = 277 parents). When examined
individually, racial/ethnic match was unrelated, but higher parental affinity to
mainstream American culture, higher parent education level, and greater
similarity in parent and therapist scores on affinity to mainstream American
culture were all significantly associated with greater parent-therapist co
endorsement of etiological explanations, while higher parental affinity to an
alternative/indigenous culture was significantly associated with lower co
endorsement. When examined simultaneously in one model, only parent education
level remained significantly associated. Findings suggest a complex relationship
between sociocultural factors and that attention to parent cultural affinity and
parent education level may facilitate parent-therapist agreement on beliefs about
child problem causes.
PMID- 26420163
TI - Treatment of Acute Cough Due to the Common Cold: Multi-component, Multi-symptom
Therapy is Preferable to Single-Component, Single-Symptom Therapy--A Pro/Con
Debate.
AB - Acute viral upper respiratory tract infection, or, the common cold, affects
essentially every human being, and cough is reported as its most frequent
associated symptom. Billions of dollars are spent worldwide annually by
individuals seeking relief from this multi-symptom syndrome. Thousands of non
prescription, over-the-counter products are available worldwide, aimed at
relieving the various bothersome symptoms induced by the common cold. Differences
of opinion exist as to whether optimal therapy for cough associated with the
common cold consists of multi-component, multi-symptom cough/cold preparations,
or, whether single-component medications, aimed at relief of specific symptoms,
represent the optimal therapeutic approach. The 5th American Cough Conference,
held in Washington, D.C. in June, 2015, provided an ideal forum for discussion
and debate of this issue between two internationally recognized experts in the
field of the common cold and its treatment.
PMID- 26420165
TI - Robots and type 1 diabetes.
PMID- 26420164
TI - Adherence to Anti-tuberculosis treatment and treatment outcomes among
tuberculosis patients in Alamata District, northeast Ethiopia.
AB - BACKGROUND: Non-adherence to tuberculosis (TB) treatment can result in an
emergence of new strains, prolonged infectiousness, drug resistance and poor
treatment outcomes. Thus, assessment of the level of adherence to anti-TB
treatment, treatment outcomes and identifying factors associated with non
adherence and poor treatment outcomes are vital for improving TB treatment
adherence and treatment outcomes in the study area. The main objectives of the
current study were to assess the level of adherence to anti-TB treatment among
patients taking anti-TB drug treatment and to identify factors associated with
non-adherence. Whereas, the secondary objectives were to assess treatment
outcomes and factors associated with poor treatment outcomes among TB patients
previously treated at the health institutions of Alamata District, northeast
Ethiopia. METHODS: In a health facility-based cross-sectional study, TB patients
who were taking anti-TB drug treatment were interviewed using a structured
questionnaire to evaluate level of adherence to anti-TB treatment. TB treatment
outcomes were evaluated using data generated from a record review of previous TB
patients who were treated at health facilities of Alamata District from January
2007 to June 2012. Adherence data and treatment outcomes data were computerized
separately using Epi-Data version 3.1 and analyzed using STATA version 10.0.
RESULTS: Between November 2012 and January 2013, 116 (58.0%) male TB patients and
84 (42.0%) female TB patients were interviewed, of whom 77.5% were new cases,
23.5% were smear-positive pulmonary TB (SPPTB) cases, 26.5% were smear-negative
PTB (SNPTB) cases and 50.0% were extra pulmonary (EPTB) cases. The overall
adherence rate to anti-TB treatment was 88.5%. The main reasons for the non
adherent patients were forgetting to take medication, being away from home, drug
side effects, being unable to go to the health facilities on the date of
appointment and being hospitalized. In the TB treatment outcomes component of the
current study, records of 4,275 TB patients were reviewed and the overall
treatment success rate was 90.1%. Two-hundred fifteen (5.0%) patients had
unsuccessful treatment outcomes, of whom 76 (35.3%) defaulted, 126 (58.6%) died
and 13 (6.1%) had treatment failure. Significant predictors of unsuccessful
treatment outcomes were being positive for human immunodeficiency virus (HIV)
infection [adjusted odds ratio (aOR) = 2.1, 95% CI 1.5-3.0], being SPPTB case
(aOR = 3.4, 95% CI 2.4-4.8), being SNPTB case (aOR = 2.0, 95% CI 1.5-2.8)], and
being re-treatment cases (aOR = 2.6, 95% CI 1.5-3.7). CONCLUSION: In the present
study area, there was a high level of adherence to anti-TB treatment and also a
high TB treatment success rate. However, still further effort like health
education to patient or family is needed to reduce those factors which affect
adherence and treatment success rates in order to ensure higher rates of
adherence and treatment success than the currently observed in the present study
area.
PMID- 26420166
TI - Ceftazidime-avibactam for the treatment of complicated urinary tract infections
and complicated intra-abdominal infections.
AB - Treatment of complicated urinary tract infections and complicated intra-abdominal
infections is increasingly difficult due to the rising prevalence of multidrug
resistant Gram-negative bacteria. Ceftazidime-avibactam is a combination of the
established third-generation cephalosporin ceftazidime with avibactam, a novel
non-beta-lactam beta-lactamase inhibitor, which restores the activity of
ceftazidime against many beta-lactamase-producing Gram-negative bacteria,
including extended-spectrum beta-lactamases and Klebsiella pneumoniae
carbapenemases. Clinical and nonclinical studies supporting the safety and
efficacy of ceftazidime-avibactam include microbiological surveillance studies of
clinically relevant pathogens, in vivo animal models of infection,
pharmacokinetic/pharmacodynamic target attainment analyses, Phase I clinical
pharmacology studies, and Phase II/III studies in the treatment of complicated
intra-abdominal infections and complicated urinary tract infections, including
patients with ceftazidime-nonsusceptible Gram-negative infections.
PMID- 26420167
TI - To Love is to Suffer: Older Adults' Daily Emotional Contagion to Perceived
Spousal Suffering.
AB - Objectives: For older adults coping with a spouse's chronic condition, greater
marital satisfaction may not be entirely protective for psychological health. We
examined marital satisfaction and gender as moderators of the association between
perceived spousal suffering and daily emotional contagion. Based on empathy
altruism and interdependent self-construal theories, we hypothesized that high
marital satisfaction and being female would heighten daily emotional contagion,
or within-person associations between perceived spouse suffering and distress to
spouse suffering. Method: Forty-five older adults who had a spouse with a
musculoskeletal condition completed daily interviews. Participants reported their
marital satisfaction once in the laboratory and then daily perceptions of their
spouse's physical suffering and their own distress to spouse suffering via phone
at home for 7 days. Results: Consistent with hypotheses, there were significant
within-person effects such that highly satisfied wives experienced heightened
emotional contagion on days when they perceived higher than average spouse
suffering. Unexpectedly, men who were high in marital satisfaction experienced
heightened daily distress irrespective of their perceptions of level of spousal
suffering. Discussion: Marital satisfaction can increase daily emotional
contagion to spousal suffering among older couples dealing with chronic
conditions. Wives' distress may be more dependent on perceiving high levels of
partner suffering compared with husbands' distress.
PMID- 26420168
TI - Do the classification of areas and distance matter to the assessment results of
achieving the treatment targets among type 2 diabetes patients?
AB - BACKGROUND: Type 2 diabetes is a major health concern all over the world. The
prevention of diabetes is important but so is well-balanced diabetes care.
Diabetes care can be influenced by individual and neighborhood socio-economic
factors and geographical accessibility to health care services. The aim of the
study is to find out whether two different area classifications of urban and
rural areas give different area-level results of achieving the targets of control
and treatment among type 2 diabetes patients exemplified by a Finnish region. The
study exploits geo-referenced patient data from a regional primary health care
patient database combined with postal code area-level socio-economic variables,
digital road data and two grid based classifications of areas: an urban-rural
dichotomy and a classification with seven area types. METHODS: The achievement of
control and treatment targets were assessed using the patient's individual
laboratory data among 9606 type 2 diabetes patients. It was assessed whether
hemoglobin A1c (HbA1c) was controlled and whether the recommended level of HbA1c
was achieved in patients by different area classes and as a function of distance.
Chi square test and logistic regression analysis were used for testing. RESULTS:
The study reveals that area-level inequalities exist in the care of type 2
diabetes in a detailed 7-class area classification but if the simple dichotomy of
urban and rural is applied differences vanish. The patient's gender and age, area
level education and the area class they belonged to were associated with
achievements of control and treatment targets. Longer distance to health care
services was not a barrier to good achievements of control or treatment targets.
CONCLUSIONS: A more detailed grid-based area classification is better for showing
spatial differences in the care of type 2 diabetes patients. Inequalities exist
but it would be misleading to state that the differences are simply due to urban
or rural location or due to distance. From a planning point of view findings
suggest that detailed geo-coded patient information could be utilized more in
resourcing and targeting the health care services to find the area-level needs of
care and to improve the cost-efficient allocation of resources.
PMID- 26420169
TI - Assessing the detection, reporting and investigation of adverse events in
clinical trial protocols implemented in Cameroon: a documentary review of
clinical trial protocols.
AB - BACKGROUND: International guidelines recommend ethical and scientific quality
standards for managing and reporting adverse events occurring during clinical
trials to competent research ethics committees and regulatory authorities. The
purpose of this study was to determine whether clinical trial protocols in
Cameroon are developed in line with national requirements and international
guidelines as far as detecting, reporting and investigating of adverse events is
concerned. METHODS: It was a documentary review of all approved clinical trial
protocols that were submitted at the Cameroon National Ethics Committee for
evaluation from 1997 through 2012. Data were extracted using a preconceived and
validated grid. Protocol review process targeted the title, abstract, objectives,
methodology, resources, and the chapter on safety. RESULTS: In total, 106 (4.9 %)
clinical trial protocols were identified from 2173 protocols seen in the archive
and 104 (4.8 %) included for review. Seventy six (73.1 %) trials did not include
the surveillance of adverse events as part of their objective. A total of 91
(87.5 %) protocols did not budget for adverse event surveillance, 76 (73.1 %) did
not have a data safety management board (DSMB), 11(10.6 %) included insurance for
participants, 47 (45.2 %) did not include a case definition for serious adverse
events, 33 (31.7 %) described procedures to detect adverse events, 33 (31.7 %)
described procedure for reporting and 22 (21.2 %) described procedure for
investigating adverse events. DISCUSSIONS: Most clinical trial protocols in
Cameroon are developed to focus on benefits and pay little attention to harms.
The development of national guidelines can improve the surveillance of adverse
events in clinical trial research conducted in Cameroon. Adverse events
surveillance tools and a budget are critical for an adequate planning for adverse
event surveillance when developing trial protocols. CONCLUSION: Clinical trial
protocols submitted in the Cameroon National Ethics Committee do not adequately
plan to assess adverse events in clinical trial protocols. In order to improve on
the safety of participants and marketed drug, there is a need to develop national
guidelines for clinical trials by the government, and to improve evaluation
procedures and monitoring of ongoing trials by the ethics committee.
PMID- 26420170
TI - The visual encoding of tool-object affordances.
AB - The perception of tool-object pairs involves understanding their action
relationships (affordances). Here, we sought to evaluate how an observer visually
encodes tool-object affordances. Eye-movements were recorded as right-handed
participants freely viewed static, right-handed, egocentric tool-object images
across three contexts: correct (e.g. hammer-nail), incorrect (e.g. hammer-paper),
spatial/ambiguous (e.g. hammer-wood), and three grasp-types: no hand, functional
grasp-posture (grasp hammer-handle), non-functional/manipulative grasp-posture
(grasp hammer-head). There were three areas of interests (AOI): the object
(nail), the operant tool-end (hammer-head), the graspable tool-end (hammer
handle). Participants passively evaluated whether tool-object pairs were
functionally correct/incorrect. Clustering of gaze scanpaths and AOI weightings
grouped conditions into three distinct grasp-specific clusters, especially across
correct and spatial tool-object contexts and to a lesser extent within the
incorrect tool-object context. The grasp-specific gaze scanpath clusters were
reasonably robust to the temporal order of gaze scanpaths. Gaze was therefore
automatically primed to grasp-affordances though the task required evaluating
tool-object context. Participants also primarily focused on the object and the
operant tool-end and sparsely attended to the graspable tool-end, even in images
with functional grasp-postures. In fact, in the absence of a grasp, the object
was foveally weighted the most, indicative of a possible object-oriented action
priming effect wherein the observer may be evaluating how the tool engages on the
object. Unlike the functional grasp-posture, the manipulative grasp-posture
caused the greatest disruption in the object-oriented priming effect, ostensibly
as it does not afford tool-object action due to its non-functional interaction
with the operant tool-end that actually engages with the object (e.g., hammer
head to nail). The enhanced attention towards the manipulative grasp-posture may
serve to encode grasp-intent. Results here shed new light on how an observer
gathers action-information when evaluating static tool-object scenes and reveal
how contextual and grasp-specific affordances directly modulate visuospatial
attention.
PMID- 26420171
TI - Current trends in the development of porous polymer monoliths for the separation
of small molecules.
AB - Since their introduction, the main application area of porous polymer monoliths
has been in the fast gradient separation of synthetic and natural polymers. On
the other hand, it has proven to be difficult to prepare polymer monoliths
providing column efficiency comparable with particulate and monolithic silica
based stationary phases. During this decade, several experimental approaches were
performed that aimed to improve this property of polymer monoliths. These
protocols include variation in a polymerization time and preparation of
monolithic stationary phases at limited conversion of the polymerization
reaction, application of novel, highly ordered, nanomaterials, and/or hypercross
linking surface modification controlling the cross-link density of prepared
monoliths. By using some of these approaches, monolithic stationary phases with
column efficiency reaching 200,000 plates/m for low-molecular-weight compounds
have been prepared. This review deals with preparation of polymer monoliths for
the separation of small molecules and summarizes recent development in this
field. At first, it focuses on monolithic columns morphology and repeatability of
their preparation. Then, recent results in individual experimental protocols are
discussed. Finally, possible future steps leading to the preparation of more
efficient monolithic stationary phases are outlined.
PMID- 26420173
TI - A metal-mediated boron-centred isomerisation reaction via C-H activation.
AB - A heterocyclic manganese complex (4) derived from a carbonyl-borylene coupling
reaction undergoes isomerisation, during which the former borylene moiety
migrates to the cyclopentadienyl ligand and inserts into a C-H bond. This
reaction and a computational study of its mechanism are discussed.
PMID- 26420174
TI - Combining marine macroecology and palaeoecology in understanding biodiversity:
microfossils as a model.
AB - There is growing interest in the integration of macroecology and palaeoecology
towards a better understanding of past, present, and anticipated future
biodiversity dynamics. However, the empirical basis for this integration has thus
far been limited. Here we review prospects for a macroecology-palaeoecology
integration in biodiversity analyses with a focus on marine microfossils [i.e.
small (or small parts of) organisms with high fossilization potential, such as
foraminifera, ostracodes, diatoms, radiolaria, coccolithophores, dinoflagellates,
and ichthyoliths]. Marine microfossils represent a useful model system for such
integrative research because of their high abundance, large spatiotemporal
coverage, and good taxonomic and temporal resolution. The microfossil record
allows for quantitative cross-scale research designs, which help in answering
fundamental questions about marine biodiversity, including the causes behind
similarities in patterns of latitudinal and longitudinal variation across taxa,
the degree of constancy of observed gradients over time, and the relative
importance of hypothesized drivers that may explain past or present biodiversity
patterns. The inclusion of a deep-time perspective based on high-resolution
microfossil records may be an important step for the further maturation of
macroecology. An improved integration of macroecology and palaeoecology would aid
in our understanding of the balance of ecological and evolutionary mechanisms
that have shaped the biosphere we inhabit today and affect how it may change in
the future.
PMID- 26420172
TI - Deep sequencing analysis of transcriptomes in Aspergillus flavus in response to
resveratrol.
AB - BACKGROUND: Resveratrol has been reported as a natural phytoalexin that inhibits
infection or the growth of certain fungi including Aspergillus flavus. Our
previous research revealed that aflatoxin production in A. flavus was reduced in
medium with resveratrol. To understand the molecular mechanism of the A. flavus
response to resveratrol treatment, the high-throughput paired-end RNA-Seq was
applied to analyze the transcriptomic profiles of A. flavus. RESULTS: In total,
366 and 87 genes of A. flavus were significantly up- and down- regulated,
respectively, when the fungus was treated with resveratrol. Gene Ontology (GO)
functional enrichment analysis revealed that 48 significantly differentially
expressed genes were involved in 6 different terms. Most genes in the aflatoxin
biosynthetic pathway genes cluster (#54) did not show a significant change when
A. flavus was treated with resveratrol, but 23 of the 30 genes in the #54 cluster
were down-regulated. The transcription of aflA and aflB was significantly
suppressed under resveratrol treatment, resulting in an insufficient amount of
the starter unit hexanoate for aflatoxin biosynthesis. In addition, resveratrol
significantly increased the activity of antioxidative enzymes that destroy
radicals, leading to decreased aflatoxin production. Moreover, stuA, fluG, flbC,
and others genes involved in mycelial and conidial development were down
regulated, which disrupted the cell's orderly differentiation and blocked conidia
formation and mycelia development. The transcripts of laeA and veA were slightly
inhibited by resveratrol, which may partly decrease aflatoxin production and
depress conidia formation. CONCLUSIONS: Resveratrol can affect the expression of
A. flavus genes that are related to developmental and secondary metabolic
processes, resulting in decreased aflatoxin production and conidia formation and
could also cause abnormal mycelia development. These results provide insight into
the transcriptome of A. flavus in response to resveratrol and a new clew for
further study in regulation of aflatoxin biosynthesis in A. flavus.
PMID- 26420176
TI - Effect of nutritional support on clinical outcomes in perioperative malnourished
patients: a meta-analysis.
AB - Malnutrition is an independent risk factor for complications, mortality, wound
healing, length of hospital stay, and costs. Associations between nutritional
support and surgical patients remain controversial. Databases, including Pubmed,
EMBASE, Web of Science, CNKI, VIP, and the Cochrane Library, were searched to
find randomized controlled trials (RCTs) that assessed the effect of nutritional
support on clinical outcomes in perioperative malnourished patients. The
methodological quality of each included trial was assessed. A meta-analysis was
conducted with Rev Man 5.2. Fifteen RCTs, involving 3831 patients, were included
in this meta-analysis. Compared with control group, results showed that
nutritional support was more effective in decreasing the incidence of infectious
[relative risk (RR): 0.58; 95% CI: 0.50, 0.68; p<0.01] and non-infectious
complications (RR: 0.74; 95% CI: 0.63, 0.88; p<0.01), and shortening the length
of hospital stay [weighted mean difference (WMD): -2.64; 95% CI: -5.13, -0.16;
p<0.05]. Moreover, the incidence of infectious complications in the immune
nutrition group was significantly lower than that in the standard nutrition group
(RR: 0.75; 95% CI: 0.58, 0.97; p<0.05). However, changes in hospital costs (WMD:
894; 95% CI: -1140, 2928; p>0.05) and postoperative mortality (RR: 0.77; 95% CI:
0.41, 1.44; p>0.05) between the nutritional support group and control group were
not significantly different. In conclusion, perioperative nutritional support was
superior in improving clinical outcomes in malnourished patients, which could
significantly reduce the incidence of complications and effectively shorten the
length of hospital stay.
PMID- 26420175
TI - Cutoff value of HbA1c for predicting diabetes and prediabetes in a Chinese high
risk population aged over 45.
AB - OBJECTIVE: To evaluate the cutoff value of HbA1c for predicting diabetes and
prediabetes in a Chinese high risk population aged over 45. METHODS: A total of
619 people aged over 45 without diabetes were randomly recruited to complete
Finnish Diabetes Risk Score (FINDRISC) questionnaire. 208 high-risk individuals
(defined by Diabetes Risk Score >=9) had OGTT and HbA1c determined at the same
time. RESULTS: In a Chinese population aged over 45, the best cutoff value of
HbA1c for detecting diabetes and prediabetes was 5.8% and 5.4% respectively. The
area under the receiver operating characteristic (AUROC) curve of HbA1c for
detecting diabetes was 0.85 (95% CI: 0.80-0.90) and prediabetes was 0.62 (95% CI:
0.54-0.70). The combined use of HbA1c and fasting blood glucose (FPG) had larger
AUROC than HbA1c alone (0.88, 95%CI: 0.83-0.92 in detecting diabetes vs 0.75, 95%
CI: 0.67-0.82 in prediabetes), and had a higher sensitivity in predicting
diabetes and higher specificity and positive predictive value (PPV) in predicting
prediabetes. However, the AUROC between HbA1c alone and combined use in
predicting diabetes was not significantly different (p=0.173). CONCLUSIONS:
FINDRISC is feasible tool to screen people who are at high risk of diabetes. The
cutoff values of HbA1c to diagnose diabetes and prediabetes in a Chinese high
risk population aged over 45 were 5.8% and 5.4%, respectively. The sensitivity
and specificity of HbA1c for detecting diabetes and prediabetes was relatively
low, so that the combined use of HbA1c and FPG may be more effective in
prediction.
PMID- 26420178
TI - Dietary or enteral medium-chain triglyceride usage in a Chinese general hospital.
AB - OBJECTIVES: Medium chain triglycerides (MCTs) are of nutritional interest for
their unique properties on ingestion, absorption and metabolism. However, dietary
and enteral MCTs usage in hospitalized patients in China requires evaluation.
METHODS: A retrospective analysis was conducted on 46 hospitalized patients who
were administered MCTs therapy between January, 2012 and December, 2013 in Peking
Union Medical College Hospital. The clinical parameters of subjects were
evaluated 2 weeks after intervention. All indications and outcomes of MCTs
therapy underwent evidence-based evaluation. A survey was conducted on a random
sample of 77 doctors to clarify the awareness and knowledge of MCTs therapy among
clinicians. RESULTS: Among 46 cases undergoing MCTs therapy, there were 21 with
gastrointestinal dysfunction (with improvement in 15 cases), 15 with lymphatic
anomalies (with improvement in 7 cases), 5 with dyslipidemia (with improvement in
3 cases), 4 with exocrine pancreatic insufficiency (with improvement in 2 cases)
and 1 with epilepsy (without improvement). All indications were evidence -based.
Although MCTs were being utilized in an increasing number of patients, the survey
revealed poor knowledge of their physicochemical properties, medical indications
and the therapeutic basis of their use among clinicians. CONCLUSIONS: MCTs
therapy is of benefit in the management of gastrointestinal malabsorption,
pancreatic exocrine insufficiency, intestinal lymphangiectasia and dyslipidemia.
However, randomized controlled trials with adequate sample size and longer follow
up are required to evaluate further their efficacy, and more educational programs
are needed to ensure clinical competence for MCT therapy.
PMID- 26420177
TI - Emerging malnutrition during hospitalisation independently predicts poor 3-month
outcomes after acute stroke: data from a Chinese cohort.
AB - OBJECTIVE: Questions exist regarding the causal relationship between malnutrition
and stroke outcomes. This study aimed to determine whether nutritional status
changes or malnutrition during hospitalisation could predict 3-month outcomes in
acute stroke patients. METHODS: During a 10-month period, patients who suffered
their first stroke within 7 days after stroke onset were included in this
prospective multi-centre study. The demographic parameters, stroke risk and
severity factors, malnutrition risk factors and dysphagia were recorded.
Nutritional status was assessed by 3 anthropometric and 3 biochemical indices.
Changes in nutritional status were defined by comparing the admission values with
the 2-week values. A Modified Rankin Scale score of 3-6 was defined as a poor
outcome at the 3-month follow-up. Univariate and multiple logistic regression
analyses were used to investigate the power of nutritional status changes in
predicting poor patient outcomes. RESULTS: Data from 760 patients were analysed.
Poor outcomes were observed in 264 (34.7%) patients. Malnutrition prevalence was
3.8% at admission and 7.5% after 2-weeks in hospital, which could not predict 3
month outcome. Emerging malnutrition was observed in 36 patients (4.7%) during
the 2-week hospitalisation period and independently predicted poor 3-month
outcomes after adjusting for confounding factors (odds ratio 1.37, 95% confidence
interval 1.03-1.83). CONCLUSIONS: Emerging malnutrition during hospitalisation
independently predicted poor 3-month outcomes in acute stroke patients in this
study.
PMID- 26420179
TI - Glucose absorption in nephropathy patients receiving continuous ambulatory
peritoneal dialysis.
AB - OBJECTIVES: Peritoneal dialysis patients are at risk of glucose absorption from
peritoneal dialysate, not only because of energy imbalance but also the toxic
effects of high glucose. The current widely applied formulae may be not suitable
for estimation of glucose absorption in continuous ambulatory peritoneal dialysis
(CAPD) patients. This study examined the actual glucose absorption in a cohort of
CAPD patients and compared the results with estimates from four current formulae.
METHODS: We conducted a survey of glucose absorption of a cohort of 72 CAPD
patients and compared actual dialysate glucose absorbed and estimates using
K/DOQI formula, Grodstein formula, Bodnar formula, or a percentage estimate of
60%. RESULTS: The total dialysate glucose infused each day varied from 54.4 to
191 g/day with average of 102+/-27.9 g. The average of glucose absorbed was 65.7
g (ranging from 19.5 to 131 g) by actual measurements. The mean absorption rate
was 64.4% (ranging from 30.6% to 92.4%). The glucose absorbed from dialysate
accounted for 13.8% (ranging from 5.0% to 30.1%) of total energy intake. The
average errors of absolute values between actual measurements and estimates were
greater than 10 g or 20 g glucose (p<0.001). The average errors in percentages
were greater than 20% or 40%, dependently on estimating methods. CONCLUSIONS: The
applications of current estimating methods may have limitations. The actual
measurement provides dietitians and doctors with more exact information of
absorbed glucose and energy compared to the current estimating methods.
PMID- 26420180
TI - Effect of vitamin B-12 and n-3 polyunsaturated fatty acids on plasma
homocysteine, ferritin, C-reaction protein, and other cardiovascular risk
factors: a randomized controlled trial.
AB - OBJECTIVES: Vitamin B-12 and n-3 polyunsaturated fatty acids (PUFA) decrease
blood homocysteine (Hcy) concentrations. However, the combined effect of these
nutrients on Hcy and ferritin, and C-reactive protein is limited and
inconclusive. The objective was to examine the synergistic effect of vitamin B-12
in combination of n-3 PUFA on plasma Hcy, ferritin, and other biochemical
markers. METHODS: In a randomized controlled trial, thirty eligible subjects were
randomly divided into three groups, and assigned to receive 1000 MUg of vitamin B
12, 2 g fish oil, or 1000 MUg vitamin B-12 and 2 g fish oil, respectively, for 8
weeks. Plasma phospholipids (PL) fatty acids and biochemical markers were
determined. This study was registered under ClinicalTrials.gov Identifier:
NCT01762072. RESULTS: Plasma PL 20:5n-3, 22:6n-3 and n-3 PUFA was increased after
4 and 8 week supplementation of fish oil, and vitamin B-12+fish oil. Plasma
concentrations of triacylglycerol, uric acid, C-reactive protein, and ferritin
were significantly decreased after 4 and 8 week supplementation of fish oil, and
vitamin B-12+fish oil. In all groups, significant changes in plasma Hcy were
observed during the study period. Vitamin B-12, fish oil, and vitamin B-12+fish
oil supplementation lowered plasma Hcy concentrations by 22%, 19%, and 39%,
respectively. CONCLUSIONS: The combination of vitamin B-12 and fish oil has a
synergistic effect on lowering plasma concentrations of Hcy.
PMID- 26420181
TI - Effects of supplementation with a combination of beta-hydroxy-beta-methyl
butyrate, L-arginine, and L-glutamine on postoperative recovery of quadriceps
muscle strength after total knee arthroplasty.
AB - OBJECTIVES: Total knee arthroplasty (TKA) performed in knee osteoarthritis
patients is reported to be immediately followed by a decrease in quadriceps
muscle strength. We investigated the effects of supplementation with a
combination beta-hydroxy-beta-methyl butyrate, L-arginine, and L-glutamine
(HMB/Arg/Gln) on the postoperative recovery of quadriceps muscle strength in
patients after TKA. METHODS: Study subjects were 23 patients (12 women; mean age:
70.5) who underwent TKA. The patients were randomly allocated into the control
group or the group that consumed HMB/Arg/Gln supplementation (HMB/Arg/Gln group).
HMB/Arg/Gln supplementation or control food were consumed for 5 days before the
surgery and for 28 days after the surgery, and maximal quadriceps strength was
measured at 7 days before the surgery, and at 14, 28 and 42 days after the
surgery. During the study, total energy expenditure was measured using a
lifestyle recording device. The two groups followed the rehabilitation in the
same way. RESULTS: The maximal quadriceps strength was 1.1+/-0.62 Nm/Kg before
surgery and 0.7+/-0.9 Nm/Kg after surgery 14 days in the control group (p=0.02),
and 1.1+/-0.3 Nm/Kg before surgery and 0.9+/-0.4 Nm/Kg after surgery 14 days in
the HMB/Arg/Gln group. Although the control group experienced a significant loss
of muscle strength after the surgery, the HMB/Arg/Gln group did not. There was no
significant difference in total energy expenditure between the two groups.
CONCLUSIONS: Consuming HMB/Arg/Gln supplementation may suppress the loss of
muscle strength after TKA. Intervention with exercise and nutrition appears to
enable patients to maintain their quadriceps strength.
PMID- 26420182
TI - Encapsulated green kiwifruit extract: a randomised controlled trial investigating
alleviation of constipation in otherwise healthy adults.
AB - OBJECTIVES: Previous clinical trials have shown bowel function is improved
through consumption of whole kiwifruit (Actinidia deliciosa). This study
investigated whether encapsulated kiwifruit extract (1 g/day) could alleviate
constipation in otherwise healthy adults. METHODS: Forty adults with confirmed
constipation entered this trial, of which 32 completed with >80% compliance. Two
capsules were self-administered morning and evening for 2 periods, each of 3
weeks duration, separated by a 3+ week washout in a double blind, randomised,
placebo controlled crossover. Inclusion criteria included constipation with <=3
bowel movements (BM) per week. Daily records of defecation frequency and stool
characteristics were obtained throughout treatment, as well as a measurement of
gastrointestinal symptoms rating scale (GSRS) and quality of life (QoL) before
and after each intervention arm. RESULTS: There was no difference in total BM
over 3 weeks (p>0.05) or mean BM during each of weeks 1, 2 and 3 (p>0.05) between
the kiwifruit extract and placebo when assessed from a faecal diary. There was
also no detectable difference in defecation related scores of BM ease of
defecation, volume, consistency or BM type assessed using Bristol stool chart
scores. Nor was there a significant change in GSRS or QoL between pre and post
treatment measures, when compared to placebo (p>0.05). CONCLUSIONS: This trial
showed that improvement in bowel function or comfort was not achieved through
supplementation with 1 g/day freeze dried kiwifruit extract. Efficacy from prior
kiwifruit powder and whole fruit trials indicate that investigating higher doses
of encapsulated kiwifruit extract may be worthwhile.
PMID- 26420183
TI - Determinants of dietary self-care behaviours among Taiwanese patients with type 2
diabetes.
AB - The effects of patient characteristics on reported adherence to dietary self-care
behaviours in 184 Taiwanese outpatients 40 years or older with type 2 diabetes
was assessed. Patient characteristics included the presence of predisposing
factors affecting diabetes adherence (knowledge and attitudes about the disease,
self-efficacy, and the absence of psychological problems), enabling factors
(understanding of diabetes and environmental factors affecting it), and
reinforcing factors (presence of medical and social support) which were evaluated
using a 72 item self-administered questionnaire with 8 subscales. Adherence was
assessed by patients' reports of carrying out 7 self-care behaviours (following a
diabetic meal plan, following the diabetes exchange system, eating meals
providing the same amount of carbohydrate every day, counting carbohydrates,
reducing dietary fat, consuming high fiber foods, and keeping a daily food
record). Reported adherence ranged from 17% to 74%. No single predisposing,
enabling, or reinforcing factor predicted adherence to all of the dietary self
care behaviours. However, more self-efficacy, better understanding, and a better
attitude toward diabetes were associated with performing five or more of the
dietary self-care behaviours examined. With respect to specific self-care
behaviours, women were more likely than men to count carbohydrates (OR=5.75) and
reduce fat in their diets (OR=2.57). Patients who attended more nutrition
education sessions were more likely to follow diabetes meal plans (OR=2.11) and
the diabetes exchange system (OR=3.07). Efforts are needed to encourage providers
to teach diabetes self-care behaviours to patients and to capitalize upon
demographic and psychosocial characteristics that can enhance patient adherence.
PMID- 26420184
TI - Diabetes self-care behaviours and clinical outcomes among Taiwanese patients with
type 2 diabetes.
AB - We examined the influences of patients' background characteristics on the
frequency of performing five diabetes self-care behaviours that 185 Taiwanese
outpatients reported. All patients had type 2 diabetes diagnosed for more than a
year and attended an outpatient clinic at a large university hospital where they
had received at least one dietitian-led individual nutrition education session
and one nurse-led diabetes education session during the course of their care.
Seventy nine percent of the patients regularly (defined as responses often or
always on the questionnaire) took their medications and over half followed
recommended meal plans and exercised, but fewer performed foot care (38%) or
checked their blood glucose levels (20%) regularly. The associations between
patients' demographics and disease-related characteristics and their performance
of self-care behaviours were assessed with logistic regression. Although checking
blood glucose levels and performing diabetes foot care were unrelated to any
clinical outcome examined, patients who took their diabetes medications had lower
hemoglobin A1c levels and fewer chronic complications than those who did not.
Furthermore, patients who followed a diabetes meal plan also had lower hemoglobin
A1c levels, and those who exercised regularly had healthier body mass indices
(BMI) than those who did not.
PMID- 26420185
TI - Low haemoglobin levels contribute to low grip strength independent of low-grade
inflammation in Japanese elderly women.
AB - Muscle strength declines with age. However, factors that contribute to such
declines are not well documented and have not been extensively studied in elderly
populations of Asian origin. Correlations of grip strength with a broad range of
factors associated with declines in muscle strength were examined in 202
community-living elderly Japanese women. After adjustment for age, grip strength
was positively correlated with body weight, height, serum albumin, haemoglobin,
high-density lipoprotein cholesterol (HDL-C) and serum iron and inversely with
serum copper, and log high-sensitivity C-reactive protein (hsCRP). Multiple
linear regression analysis with grip strength as a dependent variable showed that
47.0% of variability of grip strength could be accounted for by height, age and
haemoglobin in order of increasing R2. In conclusion, low haemoglobin may
contribute to low muscle strength independently of age, anthropometric,
nutritional, and inflammatory markers in the elderly, and may represent an
important confounder of the association between grip strength and functional
decline in community- living Japanese elderly women.
PMID- 26420186
TI - Anaemia prevalence over time in Indonesia: estimates from the 1997, 2000, and
2008 Indonesia Family Life Surveys.
AB - OBJECTIVE: To summarize anaemia prevalence data for children, women, and men
using data from the second, third and fourth waves of the Indonesia Family Life
Surveys (IFLS), which were conducted in 1997/8, 2000, and 2007/8, respectively.
METHODS: Anaemia prevalence was determined for children 0 to 5 years, 5 to 12
years, 12 to 15 years, non-pregnant women at least 15 years, pregnant women at
least 15 years, and men at least 15 years, based on haemoglobin adjusted for
altitude and smoking status. RESULTS: Compared with 1997/8 estimates, anaemia
prevalence estimates were lower in 2007/8 for all groups, with the greatest
relative decline occurring in children 5 to 12 years (25.4%). Trend analysis
found anaemia significantly declined over the survey years for all groups (chi2
p=0.005 for pregnant women, chi2 p<0.001 for all other groups). CONCLUSIONS: IFLS
anaemia estimates for different population groups decreased between 1997/8 and
2007/8 and were consistent with estimates from Southeast Asia, and with other
studies conducted in Indonesia. While the prevalence of anaemia consistently
decreased in all groups, anaemia remains a moderate public health problem for
children 0 to 5 years, children 5 to 12 years, and non-pregnant and pregnant
women.
PMID- 26420187
TI - Intake and major sources of dietary flavonoid in Korean adults: Korean National
Health and Nutrition Examination Survey 2010-2012.
AB - With an effort to investigate possible relationship between flavonoids and
health, an accurate estimation of flavonoid intake is valuable. We estimated
dietary flavonoid intake and identified the major food sources. Subjects were
healthy adults aged >=19 y (n=11,474) who completed the 24-h dietary recall of
the Korean National Health and Nutritional Examination Survey (2010-2012). The US
Department of Agriculture and newly estimated or published values for typical
Korean foods were combined into a Korean-targeted flavonoid database. The mean
intake of total flavonoid was 107+/-1.47 mg/d, with a higher intake in women than
in men after energy-adjustment. Quercetin, cyanidin, genistein, daidzein,
epigallocatechin 3-gallate, epicatechin, hesperetin, and luteolin were identified
as major flavonoid compounds. Across the age range studied, flavonols and
flavones showed a reversed U-shape curve; flavan-3-ol and flavanones showed a
decreasing pattern; and anthocyanidins and isoflavones showed an increasing
pattern. Forty-five food items were identified as contributing >2% of at least
one flavonoid compound's intake. Kimchi was the major food source of total
flavonoids, followed by green tea, persimmons, and soybeans. Single food items
accounting for more than 50% of the intake of a specific flavonoid included
persimmons (cyanidin), green tea (epigallocatechin, epicatechin-3-gallate, and
epigallocatechin 3-gallate), black tea (thearubigin), tangerines (hesperetin and
naringenin), and onions (isorhamnetin). This study provides information on Korean
flavonoid intake to enable international comparisons, along with insight into how
the sources and intake of various flavonoids vary according to age and gender.
This work should facilitate future investigations of the association between
flavonoid intake and health.
PMID- 26420188
TI - New data for vitamin D in Australian foods of animal origin: impact on estimates
of national adult vitamin D intakes in 1995 and 2011-13.
AB - OBJECTIVES: To assess the potential dietary supply of vitamin D to Australian
adults by application of new data for Australian primary foods of animal origin.
METHODS: New published analytical data on the vitamin D contents of Australian
primary foods from animal products were obtained and assessed for reliability.
Using food consumption data from Australian population dietary surveys for 1995
and 2011-2013, estimates were made of the likely average daily intakes of vitamin
D equivalents from these sources by Australian adults. RESULTS: Meats, chicken,
fish, eggs and dairy produce may alone have contributed about 4.2 MUg vitamin D
equivalents per day to average Australian diets of adults >18 years in 1995 and
4.3 MUg in 2011-2013. CONCLUSIONS: Dietary vitamin D intake in Australia is
likely to be higher than previously estimated because new data from improved
analytical methods reveal the contributions to vitamin D supply from foods of
animal origin. Absence of reliable vitamin D data for milk and milk products, and
the gaps in vitamin D data for many commonly consumed seafood, poultry, eggs and
processed animal products greatly limit estimation of dietary vitamin D intakes
by Australians.
PMID- 26420190
TI - The correlation between high body mass index and survival in patients with
esophageal cancer after curative esophagectomy: evidence from retrospective
studies.
AB - OBJECTIVE: To investigate the predictive value of high body mass index (H-BMI) on
the survival of patients with esophageal cancer (EC) after curative
esophagectomy. METHODS: Studies were systematically identified to investigate the
relationship between overweight and obese (H-BMI) and clinical outcomes in EC
patients treated with curative esophagectomy. Measured clinical outcomes were
disease-free survival (DFS) and overall survival (OS). The pooled hazard ratio
(HR) with 95% confidence interval (CI) was estimated. Subgroup analyses were
performed according to tumour type and body mass index (BMI). RESULTS: Fourteen
studies with 4823 cases were included in the final pooled quantitative analysis.
In EC patients overall, H-BMI was associated with improved DFS (HR, 0.83; 95% CI:
0.75-0.90) and OS (HR, 0.79; 95 % CI: 0.73-0.85), as compared with normal BMI.
The results were consistent with those who were overweight. Among patients with
esophageal adenocarcinoma (EAC), a better prognosis, as reflected by OS, was
observed with H-BMI (HR, 0.81; 95% CI: 0.73-0.89). The same results were also
observed in EAC patients who were obese and overweight. In contrast, among
patients with esophageal squamous cell carcinoma (ESCC), H-BMI was associated
with a worse prognosis, as reflected by DFS (HR, 2.26; 95% CI: 1.29-3.24).
CONCLUSIONS: H-BMI has distinctly different impacts on the postoperative survival
of EAC and ESCC patients. H-BMI is a potential predictor for better prognosis in
EC patients overall, and particularly in EAC patients, treated with curative
esophagectomy. However, in ESCC patients, H-BMI is a potential predictor for a
worse prognosis of postoperative survival.
PMID- 26420189
TI - BMI and all-cause mortality among Chinese and Caucasians: the People's Republic
of China and the Atherosclerosis Risk in Communities Studies.
AB - BACKGROUND: Lower ethnic-specific body mass index (BMI) cutpoints have been
proposed for Asians and adapted in some countries. However, to our knowledge, no
study has directly compared Asians to other ethnic groups to test differences in
associations between BMI and all-cause mortality using common methods.
OBJECTIVES: We estimated the association between BMI and all-cause mortality in
Chinese Asians and Caucasian Americans to determine if lower Asian-specific BMI
cutpoints are warranted. METHODS: Extant data of the People's Republic of China
Study (1983-1997) including 5546 Chinese and the Atherosclerosis Risk in
Communities Study (1987-2002) including 9932 Caucasians aged 45-64 years at
baseline were used. All analyses were performed using Cox proportional regression
models. RESULTS: Standardized mortality rates were 6.88 (95% confidence interval
(CI): 5.75-8.24) and 5.50 (95% CI: 4.74-6.39) per 1000 person-years for Chinese
and Caucasians, respectively. Standardized mortality probabilities by age 70 were
similar across all BMI categories among Chinese. Furthermore, the probabilities
were similar to those among Caucasians with BMI of 27.5-<32.5 kg/m2. The BMI
associated with lowest mortality risk was almost identical between Chinese (25.1
kg/m2) and Caucasians (25.2 kg/m2). The analysis of categorical BMI did not
reveal an increased mortality risk at any BMI category among Chinese. In
contrast, compared to those with a BMI of 23.0-<25.0 kg/m2, risk was elevated by
35% among Caucasians with a BMI of 30.0-<32.5 kg/m2. CONCLUSIONS: These findings
do not support different BMI cutpoints for Chinese than Caucasians on the basis
of mortality rates.
PMID- 26420191
TI - Interrelationship between glucose metabolism and undercarboxylated osteocalcin: a
cross-sectional study in a community-dwelling population.
AB - OBJECTIVE: Undercarboxylated osteocalcin (ucOC) produced from the bone was
recently found to play a regulatory role in the insulin and adiponectin
secretion. We performed a cross-sectional study to investigate the relationship
between ucOC and diabetes mellitus (DM). METHODS: We included 1,870 subjects aged
over 50 from participants of a health examination. According to the current
medication and past history, 605 subjects had hypertension (HT), 316 had
dyslipidemia (DL), and 182 had type 2 DM. Fasting blood samples were collected to
measure concentrations of ucOC and the bone turnover marker, tartrate-resistant
acid phosphatase 5b (TRACP5b) by ELISA. RESULTS: The serum ucOC level was
significantly lower in DM(+) than DM(-) in both men and women. In a logistic
regression analysis, a low level of ucOC was significantly associated with the
presence of DM in both men and women after adjusting for age, BMI, serum
creatinine, triglyceride, and TRACP5b. Multiple regression analysis showed a
negative association of ucOC with HbA1c and fasting plasma glucose, and a
positive association with the insulin level. In contrast, no association was
found between TRACP5b and the indices above, suggesting that the effect of ucOC
on the insulin secretion and the glycemic status was independent of bone
turnover. CONCLUSIONS: The present cross-sectional study showed a significant
association between ucOC and glucose metabolism after correction with bone
turnover in a community-dwelling population both in men and women, indicating
that ucOC may play an important role in the pathogenesis of DM through the
pathways independent of bone metabolism.
PMID- 26420192
TI - A meta-analysis combining parallel and cross-over randomized controlled trials to
assess impact of iodine fortified foods on urinary iodine concentration among
children.
AB - The purpose of this analysis was to combine evidence from parallel and cross-over
randomized controlled trials to assess the impact of iodine fortified foods on
urinary iodine concentration (UIC) in children. A structured search for studies
on iodine intervention studies on MEDLINE, Pro Quest, and the Cochrane Library
from Jan, 1990 to Dec, 2012 was carried out. Carry-over effect was estimated by
general linear model. We explored two methods to pool continuous outcomes in a
meta-analysis by combining parallel and cross-over trial designs. The standard
mean difference was calculated for net change in UIC. Fixed or random-effects
models were used to summaries fortified food response data. Meta-regression and
covariate meta-analysis were performed to explore the influ-ence of confounders
on the net pooled effect on UIC. The overall pooled estimate, which combined
parallel with cross-over trials in the absence of carry-over effect of UIC from 9
studies, showed a significant increase in the fortified group compared with the
control group (n=3448; standard mean difference=2.02 MUg/L; 95% CI: 1.30, 2.73;
I2=99%, tau2=1.81, p<0.01). Meta-regression analysis indicated that dose of the
feeding was positively related to the effect size (regression coefficient=0.014;
95% CI: 0.003, 0.026; p<0.019). The net pooled effect size after removing the
confounders was 1.59 (95% CI: 0.953, 2.23) MUg/L. There was an association
between intakes of io-dine fortified foods and UIC in children. These results
suggest that we can combine parallel with cross-over trials for meta-analysis for
nutrients such as iodine when absorption is high.
PMID- 26420193
TI - Standard values of rapid turnover proteins and zinc in Japanese children.
AB - Measurement of rapid-turnover proteins has an established place in nutrition
assessment and is partly dependent on the zinc metallo-enzymes involved. We
investigated the reference values of rapid turnover proteins and zinc in Japanese
children. This cross-sectional study was conducted at a single center. We
collected data from children aged 0 to 12 years with inguinal hernia, umbilical
hernia, or hydrocele of the spermatic cord, who had body mass index z scores of
2 to 2. The standard references (mean+/-2 SD) of transthyretin were 11.5-21.5
mg/dL in infants (<=1.5 years), 13.6-21.5 mg/dL in preschool children (1.6-6
years), and 12.3-23.4 mg/dL in preadolescent children (6.1-12 years). The
standard references of retinol binding protein were 1.27-2.55 mg/dL, 1.28-2.54
mg/dL, and 1.27-2.44 mg/dL in each age group, respectively. Rapid turnover
proteins did not differ significantly in each group. The transthyretin level was
weakly correlated with aging (r=0.284, p=0.003) and estimated lean body mass
(r=0.274, p=0.004). Retinol-binding protein was not correlated with aging and
anthropometric parameters. We established reference values for rapid turnover
proteins with known zinc status in Japanese children. These values were not, or
only weakly, correlated with anthropometric parameters for assessing protein
energy malnutrition.
PMID- 26420194
TI - Is parental body weight related with their children's overweight and obesity in
Gao Hang Town, Shanghai?
AB - OBJECTIVES: This study aimed to evaluate the relationship between parental body
weight and their children's overweight and obesity in school students in Gao Hang
Town, Shanghai. METHODS: A cross-sectional study was performed in five primary
schools in Gao Hang Town, Shanghai. Overall, 2,025 sets of parents and their
children (7-13 years, 981 boys/1044 girls) were enrolled. Body mass index (BMI)
and waist circumference for each child were measured. Age, gender, birth weight,
and breastfeeding history was recorded for each child and the BMI of their
parents was obtained by a self-completion questionnaire. Overweight (including
obesity) was defined as a BMI of >=24.0 kg/m2 in parents and a BMI >=P85 in
children according to age- and gender-specific percentiles. Re-sults: The total
prevalence of overweight was higher in boys than in girls (35.5% vs 19.5%), while
it was the same in fathers compared with mothers (50.6% vs 18.9%). The prevalence
of overweight in boys showed a trend with increasing age, but remained stable
versus age in girls. Parents were further divided into four subgroups as follows:
I) both father and mother had a normal BMI; II) father overweight, mother normal
weight; III) father normal weight, mother overweight; IV) both father and mother
are overweight. The odds ratio of overweight was 2.26 for group II, 2.71 for
group III, and 4.36 for group IV, respectively, compared with group I. Gender,
paternal BMI, and maternal BMI were chosen as risk factors for children
overweight. CONCLUSIONS: Parental BMI affects their offspring overweight and
obesity in Chinese school students.
PMID- 26420195
TI - Polychlorinated biphenyl and heavy metal exposures among fishermen in the Straits
of Malacca: neurobehavioural performance.
AB - The aim of this study was to determine the level of exposure to polychlorinated
biphenyls (PCBs) and selected heavy metals among fishermen via dietary intake of
fish and other seafood from the eastern coast along the Straits of Malacca. This
study determined the neurobehavioural performances (based on neurobehavioural
core test battery scores) of the fishermen and evaluated the correlations between
scores of neurobehavioural core test battery and exposure factors. Ninety
fishermen participated in the study. The total fish intakes of the fishermen were
measured using a set of food frequency questionnaires. The PCBs contents in the
seafood samples ranged between 0.2 and 0.6 pg/g fresh sample. The concentrations
of mercury (Hg), arsenic (As), cadmium (Cd), and lead (Pb) in the seafood samples
were 1.1-5.4, 0.3-4.4, 0.6-36.1, and 0.02-0.3 MUg/g fresh sample, respectively.
The PCBs, Hg, As, Cd, and Pb exposures of the fishermen was estimated to be 2.8,
0.02, 4.5, 0.09, and 0.5 pg/kg body weight/day, respectively. PCB and heavy metal
exposures through dietary intake of fish and seafood were within the tolerable
daily limits. The results of neurobehavioural core test battery revealed that the
neurobehavioural performances of the fishermen were not affected due to PCB and
heavy metal intoxication. No correlations were found between the exposure and
neurobehavioural performance among the fishermen. These data are useful for
policy makers to assure the safety and quality of seafood in relation to sea
pollution. Although the levels of exposure were low, periodic assessment of the
quality of fish and fish products is required due to the polluted seawater.
PMID- 26420196
TI - Effectiveness of a public dietitian-led diabetes nutrition intervention on
glycemic control in a community setting in China.
AB - OBJECTIVE: Diabetes mellitus requires lifelong treatment, most of which is
accomplished in family and community settings. The present study was designed to
identify the effectiveness of nutrition intervention provided by public dietitian
on glycemic control in a community setting in China. METHODS: Two communities
were selected and randomly assigned to a routine care group (59 subjects) and a
public dietitian-led intervention group (58 subjects) who received diabetic
nutrition management for one year. The main measures included fasting plasma
glucose, HbA1c, weight, body mass index (BMI), lipid profile, and blood pressure.
RESULTS: In the intervention group, there was significant improvement in fasting
plasma glucose, HbA1c, cholesterol, and triglyceride levels relative to the
control subjects (p<0.05). Over the 12-month period, there was a decrease in
energy intake, including reductions in absolute amounts (grams) of protein and
fat in the intervention group. The energy percent values of carbohydrate,
protein, and fat were 50.7%, 17.0%, and 32.3%, respectively, at baseline and
53.0%, 17.1%, and 29.9% (within the recommended range) after the intervention.
There were significant improvements in total energy, absolute amounts of fat and
protein, and the energy percent values of carbohydrates and fat. In the control
group, however, these values were similar before and after the intervention, and
the energy percent values of fat were still above the recommended range.
CONCLUSIONS: In a community setting, a diabetes nutrition intervention led by a
public dietitian significantly improved the glycemic control of type 2 diabetic
patients.
PMID- 26420197
TI - Identifying barriers to the implementation of nutrition education in South Korea.
AB - To improve the nutritional status of children and adolescents, it is critical to
identify the barriers to the implementation of nutrition education in schools. We
carried out a cross-sectional study by analyzing data from 121 subjects (45
nutrition teachers and 76 school dietitians). Among the personal, environmental
and systematic barriers, the top four barriers to the implementation of nutrition
education were heavy workload (4.28 points), lack of a systematic curriculum
(4.12 points), lack of perception of nutrition education by school administrators
and teachers (4.07 points), and lack of continuing education for nutrition
teachers and school dietitians (4.05 points). Additionally, poor working
conditions, such as low pay, were identified as significant barriers to nutrition
education for school dietitians compared with nutrition teachers (4.33 vs 3.47
points, p<0.001). This research provides useful information for nutrition policy
makers to promote nutrition education in schools in South Korea.
PMID- 26420198
TI - The adherence of packaged food products in Hyderabad, India with nutritional
labelling guidelines.
AB - BACKGROUND: India is experiencing a nutrition transition with the consumption of
processed foods rapidly increasing. Nutrition labels are essential if consumers
are to understand the healthiness of these products. The Food Safety and
Standards Authority of India have recently introduced regulation defining
national nutrition labelling requirements and Codex Alimentarius recommends a
global standard. OBJECTIVES: To quantify the adherence of the declared nutrients
on Indian packaged foods with national and global requirements. METHODS: The
presence or absence of data for seven required nutrients was recorded for all
food products available for sale. Branches of three major retail chains and three
smaller stores in Hyderabad, India between October and November, 2010 were
surveyed. RESULTS: Data were collected for 4166 packaged products that fell into
14 different food groups. 52% of products displayed nutrient information on
energy, protein, carbohydrate, sugar and total fat, meeting the minimum
requirements of the Food Safety and Standards Authority of India. Only 27% met
the minimum criteria defined by Codex which also requires the reporting of
saturated fat and sodium. There was significant variation in compliance for
leading brands, country of manufacture and food group (p<0.01 for all).
CONCLUSIONS: The majority of Indian packaged foods do not meet national and
international nutrient labelling guidelines. With the Indian population likely to
consume much more packaged food over coming years full and effective food
labelling will be essential. The failure of Indian legislation to require
labelling of sodium and saturated fat may warrant review.
PMID- 26420199
TI - Diets high in carbohydrate may not be appropriate for rs328 G carriers with the
metabolic syndrome.
AB - The objective of this study was to test how the genetic polymorphisms located
within the lipoprotein lipase (LPL) locus would modulate the relationship between
a diet high in carbohydrate and insulin resistance related traits in metabolic
syndrome adults. A one year nutritional intervention study focusing on education
to increase dietary intake of whole grain, vegetable and fruit, and to reduce the
intake of sodium, simple sugar and dietary fat (especially cooking oil and pork
lard) was conducted. Two districts in Shanghai, China were randomly selected to
be the intervention and control group, and patients (n=235) with metabolic
syndrome within these two districts were selected based on a multistage sampling
method. Fasting glucose was reduced in rs328 CC homozygotes (p=0.028) but not G
carriers (p=0.686) within the intervention group. Also an ancillary study with
greater statistical power by combining the baseline measurements across both the
intervention and control groups was conducted to test the cross-sectional
statistical interactions between carbohydrate/fat and lipoprotein lipase
genotypes for homeostasis model assessment of insulin resistance/insulin/fasting
glucose. Increased carbohydrate intakes were positively associated with
homeostasis model assessment of insulin resistance and insulin in rs328 G
carriers but not CC homozygotes (p for interaction was 0.025). These results
indicate that diet high in carbohydrate may not be suitable for metabolic
syndrome rs328 G carriers, calling for the development of personalized dietary
intervention for metabolic syndrome subjects.
PMID- 26420200
TI - Diaceno[a,e]pentalenes: An Excellent Molecular Platform for High-Performance
Organic Semiconductors.
AB - Three diaceno[a,e]pentalene analogues with pendant sterically bulky di-tert
butylphenyl groups have been designed and synthesized. With the extension of the
conjugated molecular framework, the molecular arrangement is apparently tuned by
the balance between the pi-extended surface and pendant alkyl or aryl
substituents. Theoretical calculations of the morphologies were in good agreement
with the experimental results. Ambient-stable field-effect transistors based on
dianthraceno[a,e]pentalene (DAP) have been fabricated, which exhibited excellent
hole mobilities (up to 6.55 cm(2) V(-1) s(-1)). Thus, this study has shown that
diaceno[a,e]pentalenes are stable even with an extraordinarily large pi-surface
area, and may thus serve as excellent molecular platforms for further exploring
high-performance semiconducting materials.
PMID- 26420201
TI - Phototropic solar tracking in sunflower plants: an integrative perspective.
AB - BACKGROUND: One of the best-known plant movements, phototropic solar tracking in
sunflower (Helianthus annuus), has not yet been fully characterized. Two
questions are still a matter of debate. (1) Is the adaptive significance solely
an optimization of photosynthesis via the exposure of the leaves to the sun? (2)
Is shade avoidance involved in this process? In this study, these concepts are
discussed from a historical perspective and novel insights are provided. SCOPE
AND METHODS: Results from the primary literature on heliotropic growth movements
led to the conclusion that these responses cease before anthesis, so that the
flowering heads point to the East. Based on observations on 10-week-old plants,
the diurnal East-West oscillations of the upper fifth of the growing stem and
leaves in relation to the position of the sun (inclusive of nocturnal re
orientation) were documented, and photon fluence rates on the leaf surfaces on
clear, cloudy and rainy days were determined. In addition, the light-response
curve of net CO2 assimilation was determined on the upper leaves of the same
batch of plants, and evidence for the occurrence of shade-avoidance responses in
growing sunflower plants is summarized. CONCLUSIONS: Only elongating, vegetative
sunflower shoots and the upper leaves perform phototropic solar tracking. Photon
fluence response and CO2 assimilation measurements cast doubt on the
'photosynthesis-optimization hypothesis' as the sole explanation for the
evolution of these plant movements. We suggest that the shade-avoidance response,
which maximizes light-driven CO2 assimilation, plays a major role in solar
tracking populations of competing sunflower plants, and an integrative scheme of
these growth movements is provided.
PMID- 26420202
TI - Genetic variation facilitates seedling establishment but not population growth
rate of a perennial invader.
AB - BACKGROUND AND AIMS: Assessing the demographic consequences of genetic variation
is fundamental to invasion biology. However, genetic and demographic approaches
are rarely combined to explore the effects of genetic variation on invasive
populations in natural environments. This study combined population genetics,
demographic data and a greenhouse experiment to investigate the consequences of
genetic variation for the population fitness of the perennial, invasive herb
Lupinus polyphyllus. METHODS: Genetic and demographic data were collected from 37
L. polyphyllus populations representing different latitudes in Finland, and
genetic variation was characterized based on 13 microsatellite loci. Associations
between genetic variation and population size, population density, latitude and
habitat were investigated. Genetic variation was then explored in relation to
four fitness components (establishment, survival, growth, fecundity) measured at
the population level, and the long-term population growth rate (lambda). For a
subset of populations genetic variation was also examined in relation to the
temporal variability of lambda. A further assessment was made of the role of
natural selection in the observed variation of certain fitness components among
populations under greenhouse conditions. KEY RESULTS: It was found that genetic
variation correlated positively with population size, particularly at higher
latitudes, and differed among habitat types. Average seedling establishment per
population increased with genetic variation in the field, but not under
greenhouse conditions. Quantitative genetic divergence (Q(ST)) based on seedling
establishment in the greenhouse was smaller than allelic genetic divergence
(F'(ST)), indicating that unifying selection has a prominent role in this fitness
component. Genetic variation was not associated with average survival, growth or
fecundity measured at the population level, lambda or its variability.
CONCLUSIONS: The study suggests that although genetic variation may facilitate
plant invasions by increasing seedling establishment, it may not necessarily
affect the long-term population growth rate. Therefore, established invasions may
be able to grow equally well regardless of their genetic diversity.
PMID- 26420203
TI - Explanatory ecological factors for the persistence of desiccation-sensitive seeds
in transient soil seed banks: Quercus ilex as a case study.
AB - BACKGROUND AND AIMS: Dominant tree species in northern temperate forests, for
example oak and beech, produce desiccation-sensitive seeds. Despite the
potentially major influence of this functional trait on the regeneration and
distribution of species under climate change, little is currently known about the
ecological determinants of the persistence of desiccation-sensitive seeds in
transient soil seed banks. Knowing which key climatic and microsite factors
favour seed survival will help define the regeneration niche for species whose
seeds display extreme sensitivity to environmental stress METHODS: Using the
Mediterranean Holm oak (Quercus ilex) forest as a model system, an in situ time
course monitoring of seed water status and viability was performed during the
unfavourable winter season in two years with contrasting rainfall, at an
instrumented site with detailed climate records. In parallel, the characteristics
of the microhabitat and their influence on the post-winter water status and
viability of seeds were investigated in a regional survey of 33 woodlands
representative of the French distribution of the species. KEY RESULTS: Time
course monitoring of seed water status in natural conditions confirmed that in
situ desiccation is the main abiotic cause of mortality in winter. Critical water
contents could be reached in a few days during drought spells. Seed dehydration
rates were satisfactorily estimated using integrative climate proxies including
vapour pressure deficit and potential evapotranspiration. Seed water status was
therefore determined by the balance between water uptake after a rainfall event
and water loss during dry periods. Structural equation modelling of microhabitat
factors highlighted the major influence of canopy openness and resulting incident
radiation on the ground. CONCLUSIONS: This study provides part of the knowledge
required to implement species distribution models which incorporate their
regeneration niche. It is an important step forward in evaluating the ecological
consequences of increasing winter drought and environmental filtering due to
climate change on the regeneration of the most dominant Mediterranean tree
species.
PMID- 26420204
TI - Attack modes and defence reactions in pathosystems involving Sclerotinia
sclerotiorum, Brassica carinata, B. juncea and B. napus.
AB - BACKGROUND AND AIMS: Sclerotinia stem rot (SSR, Sclerotinia sclerotiorum) is a
damaging disease of oilseed brassicas world-wide. Host resistance is urgently
needed to achieve control, yet the factors that contribute to stem resistance are
not well understood. This study investigated the mechanisms of resistance to SSR.
METHODS: Stems of 5-week-old Brassica carinata, B. juncea and B. napus of known
resistance were infected via filter paper discs impregnated with S. sclerotiorum
mycelium under controlled conditions. Transverse sections of the stem and
portions of the stem surface were examined using optical and scanning electron
microscopy. The association of anatomical features with the severity of disease
(measured by mean lesion length) was determined. KEY RESULTS: Several distinct
resistance mechanisms were recorded for the first time in these Brassica-pathogen
interactions, including hypersensitive reactions and lignification within the
stem cortex, endodermis and in tissues surrounding the lesions. Genotypes showing
a strong lignification response 72 h post-infection (hpi) tended to have smaller
lesions. Extensive vascular invasion by S. sclerotiorum was observed only in
susceptible genotypes, especially in the vascular fibres and xylem. Mean lesion
length was negatively correlated with the number of cell layers in the cortex,
suggesting progress of S. sclerotiorum is impeded by more cell layers. Hyphae in
the centre of lesions became highly vacuolate 72 hpi, reflecting an ageing
process in S. sclerotiorum hyphal networks that was independent of host
resistance. The infection process of S. sclerotiorum was analogous in B. carinata
and B. napus. Infection cushions of the highly virulent isolate of S.
sclerotiorum MBRS-1 were grouped together in dense parallel bundles, while hyphae
in the infection cushions of a less aggressive isolate WW-3 were more diffuse,
and this was unaffected by host genotype. CONCLUSIONS: A variety of mechanisms
contribute to host resistance against S. sclerotiorum across the three Brassica
species. These complex interactions between pathogen and host help to explain
variable expressions of resistance often observed in the field.
PMID- 26420205
TI - Disturbance and density-dependent processes (competition and facilitation)
influence the fine-scale genetic structure of a tree species' population.
AB - BACKGROUND AND AIMS: Disturbances, dispersal and biotic interactions are three
major drivers of the spatial distribution of genotypes within populations, the
last of which has been less studied than the other two. This study aimed to
determine the role of competition and facilitation in the degree of conspecific
genetic relatedness of nearby individuals of tree populations. It was expected
that competition among conspecifics will lead to low relatedness, while
facilitation will lead to high relatedness (selection for high relatedness within
clusters). METHODS: The stand structure and spatial genetic structure (SGS) of
trees were examined within old-growth and second-growth forests (including multi
stemmed trees at the edge of forests) of Nothofagus pumilio following large-scale
fires in Patagonia, Chile. Genetic spatial autocorrelations were computed on a
spatially explicit sampling of the forests using five microsatellite loci. As
biotic plant interactions occur among immediate neighbours, mean nearest
neighbour distance (MNND) among trees was computed as a threshold for
distinguishing the effects of disturbances and biotic interactions. KEY RESULTS:
All forests exhibited a significant SGS for distances greater than the MNND. The
old-growth forest genetic and stand structure indicated gap recolonization from
nearby trees (significantly related trees at distances between 4 and 10 m). At
distances smaller than the MNND, trees of the second-growth interior forest
showed significantly lower relatedness, suggesting a fading of the recolonization
structure by competition, whereas the second-growth edge forest showed a positive
and highly significant relatedness among trees (higher among stems of a cluster
than among stems of different clusters), resulting from facilitation.
CONCLUSIONS: Biotic interactions are shown to influence the genetic composition
of a tree population. However, facilitation can only persist if individuals are
related. Thus, the genetic composition in turn influences what type of biotic
interactions will take place among immediate neighbours in post-disturbance
forests.
PMID- 26420213
TI - Correlation of pelvic incidence with radiographical parameters for acetabular
retroversion: a retrospective radiological study.
AB - BACKGROUND: Pelvic incidence (PI) has been linked to several degenerative
processes within the spinopelvic system. Acetabular retroversion is a recognised
risk factor for osteoarthritis of the hip. We therefore hypothesised that these
two factors might be part of a specific anatomical variant associated with
degenerative changes. This study was performed to clarify this issue. METHODS:
The pelvic incidence was measured on 589 computertomographical data sets acquired
between 2008 and 2010. For 220 patients a 2D rendering in an antero-posterior
view of the CT data set was performed to evaluate the parameters of acetabular
retroversion. Those included the prominence of the ischial spine sign (PRISS),
the cross-over sign (COS) and the posterior wall sign (PWS). Between 477 and 478
hips were evaluated depending on the parameter of retroversion. RESULTS: The mean
pelvic incidence was significantly lower in hips positive for the PRISS and the
PWS. However, there were no significant differences between hips positive or
negative for the COS. DISCUSSION: As hypothesised, the lower PI values in PWS and
PRISS positive hips suggest a link between PI and retroversion of the acetabulum.
Whether this is of any clinical relevance remains, however, unknown. CONCLUSION:
Acetabular retroversion is linked to PI. In hips where the prominence of the
ischial spine sign and/or the posterior wall sign was present, the mean pelvic
incidence value was lower.
PMID- 26420212
TI - Conserved determinants of lentiviral genome dimerization.
AB - BACKGROUND: Retroviruses selectively package two copies of their unspliced
genomes by what appears to be a dimerization-dependent RNA packaging mechanism.
Dimerization of human immunodeficiency virus Type-1 (HIV-1) genomes is initiated
by "kissing" interactions between GC-rich palindromic loop residues of a
conserved hairpin (DIS), and is indirectly promoted by long-range base pairing
between residues overlapping the gag start codon (AUG) and an upstream Unique 5'
element (U5). The DIS and U5:AUG structures are phylogenetically conserved among
divergent retroviruses, suggesting conserved functions. However, some studies
suggest that the DIS of HIV-2 does not participate in dimerization, and that
U5:AUG pairing inhibits, rather than promotes, genome dimerization. We prepared
RNAs corresponding to native and mutant forms of the 5' leaders of HIV-1 (NL4-3
strain), HIV-2 (ROD strain), and two divergent strains of simian immunodeficiency
virus (SIV; cpz-TAN1 and -US strains), and probed for potential roles of the DIS
and U5:AUG base pairing on intrinsic and NC-dependent dimerization by
mutagenesis, gel electrophoresis, and NMR spectroscopy. RESULTS: Dimeric forms of
the native HIV-2 and SIV leaders were only detectable using running buffers that
contained Mg(2+), indicating that these dimers are more labile than that of the
HIV-1 leader. Mutations designed to promote U5:AUG base pairing promoted
dimerization of the HIV-2 and SIV RNAs, whereas mutations that prevented U5:AUG
pairing inhibited dimerization. Chimeric HIV-2 and SIV leader RNAs containing the
dimer-promoting loop of HIV-1 (DIS) exhibited HIV-1 leader-like dimerization
properties, whereas an HIV-1NL4-3 mutant containing the SIVcpzTAN1 DIS loop
behaved like the SIVcpzTAN1 leader. The cognate NC proteins exhibited varying
abilities to promote dimerization of the retroviral leader RNAs, but none were
able to convert labile dimers to non-labile dimers. CONCLUSIONS: The finding that
U5:AUG formation promotes dimerization of the full-length HIV-1, HIV-2, SIVcpzUS,
and SIVcpzTAN1 5' leaders suggests that these retroviruses utilize a common RNA
structural switch mechanism to modulate function. Differences in native and NC
dependent dimerization propensity and lability are due to variations in the
compositions of the DIS loop residues rather than other sequences within the
leader RNAs. Although NC is a well-known RNA chaperone, its role in dimerization
has the hallmarks of a classical riboswitch.
PMID- 26420215
TI - The PKC/NF-kappaB signaling pathway induces APOBEC3B expression in multiple human
cancers.
AB - Overexpression of the antiviral DNA cytosine deaminase APOBEC3B has been linked
to somatic mutagenesis in many cancers. Human papillomavirus infection accounts
for APOBEC3B upregulation in cervical and head/neck cancers, but the mechanisms
underlying nonviral malignancies are unclear. In this study, we investigated the
signal transduction pathways responsible for APOBEC3B upregulation. Activation of
protein kinase C (PKC) by the diacylglycerol mimic phorbol-myristic acid resulted
in specific and dose-responsive increases in APOBEC3B expression and activity,
which could then be strongly suppressed by PKC or NF-kappaB inhibition. PKC
activation caused the recruitment of RELB, but not RELA, to the APOBEC3B
promoter, implicating noncanonical NF-kappaB signaling. Notably, PKC was required
for APOBEC3B upregulation in cancer cell lines derived from multiple tumor types.
By revealing how APOBEC3B is upregulated in many cancers, our findings suggest
that PKC and NF-kappaB inhibitors may be repositioned to suppress cancer
mutagenesis, dampen tumor evolution, and decrease the probability of adverse
outcomes, such as drug resistance and metastasis.
PMID- 26420214
TI - Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]
Pyruvate Offers Improved Metabolic Imaging of Tumors.
AB - Hyperpolarized [1-(13)C]-pyruvate has shown tremendous promise as an agent for
imaging tumor metabolism with unprecedented sensitivity and specificity. Imaging
hyperpolarized substrates by magnetic resonance is unlike traditional MRI because
signals are highly transient and their spatial distribution varies continuously
over their observable lifetime. Therefore, new imaging approaches are needed to
ensure optimal measurement under these circumstances. Constrained reconstruction
algorithms can integrate prior information, including biophysical models of the
substrate/target interaction, to reduce the amount of data that is required for
image analysis and reconstruction. In this study, we show that metabolic MRI with
hyperpolarized pyruvate is biased by tumor perfusion and present a new
pharmacokinetic model for hyperpolarized substrates that accounts for these
effects. The suitability of this model is confirmed by statistical comparison
with alternates using data from 55 dynamic spectroscopic measurements in normal
animals and murine models of anaplastic thyroid cancer, glioblastoma, and triple
negative breast cancer. The kinetic model was then integrated into a constrained
reconstruction algorithm and feasibility was tested using significantly
undersampled imaging data from tumor-bearing animals. Compared with naive image
reconstruction, this approach requires far fewer signal-depleting excitations and
focuses analysis and reconstruction on new information that is uniquely available
from hyperpolarized pyruvate and its metabolites, thus improving the
reproducibility and accuracy of metabolic imaging measurements.
PMID- 26420216
TI - An Imbalance in TAZ and YAP Expression in Hepatocellular Carcinoma Confers Cancer
Stem Cell-like Behaviors Contributing to Disease Progression.
AB - Transcriptional coactivator with PDZ-binding motif (TAZ) and yes-associated
protein (YAP) are equivalently placed downstream effectors of the Hippo pathway
with oncogenic roles in human cancers. However, the expression profiles of
TAZ/YAP differ depending on the cancer cell type, suggesting that these proteins
have different roles during cancer progression, yet no studies have examined the
biologic significance of the balance between TAZ and YAP expression levels. Here
we examined the functional roles of TAZ/YAP in hepatocellular carcinoma
progression. We found that TAZ, but not YAP, was predominantly expressed in HCC.
TAZ knockdown under normal conditions attenuated cell growth in HCC cells;
however, TAZ knockdown combined with 5-fluorouracil treatment significantly
increased chemoresistance compared with control cells. Notably, TAZ knockdown
induced compensatory YAP expression and was accompanied by upregulation of CD90,
a HCC-specific cancer stem cell marker. Continuous treatment with 5-fluorouracil
also induced YAP expression and promoted tumor formation in vivo. Conversely,
double knockdown of TAZ/YAP reduced chemoresistance and tumorigenicity. Moreover,
YAP knockdown aggravated HCC cell growth to a greater degree than TAZ knockdown,
and YAP overexpression was strongly associated with poor prognoses in patients
with HCC. Collectively, these studies demonstrate that TAZ and YAP exhibit
different functional roles in cancer progression, and a shift to predominant YAP
expression upon TAZ depletion conferred cancer stem cell-like properties
including chemoresistance and tumorigenicity in HCC. Therefore, targeting of both
TAZ/YAP will be required for a complete antitumor response in HCC.
PMID- 26420217
TI - Modeling the effect of operator and passenger characteristics on the fatality
risk of motorcycle crashes.
AB - BACKGROUND: In Iran more than 25% of crash fatalities belong to motorcycle
operators and passengers in the recent years, from which about 20% are related to
passenger fatalities. METHODS: The aim of this study was to investigate the
motorcycle operator and passenger characteristics as well as other contributory
factors that may affect the fatality risk of motorcyclists involved in traffic
crashes. To this end, motorcycle crash data between 2009 and 2012 was extracted
from Iran traffic crash database and a logistic regression analysis was performed
to obtain odds ratio estimates for each of the study variables. RESULTS: The
fatality risk of motorcyclists has a direct relationship with the number of
pillion passengers carried. Results also indicate that the amount of increase in
the likelihood of having a fatality in a motorcycles crash is considerably higher
when the operator is accompanied by a male passenger of the same age.
Furthermore, results showed that if the crash is occurred in the darkness, on
curves, in rural areas and on highways, then the crash would be more likely to be
fatal. Moreover, the head-on collisions, older operators, unlicensed operators
and not using a safety helmet were found to increase the likelihood of a fatality
in a motorcycle crash. CONCLUSIONS: Preventative measures such as, imposing
stricter rules regarding safety helmet usage and confining the number of pillion
passengers to one, might be implemented to reduce the fatality risk in motorcycle
crashes. In addition, more appropriate infrastructures for penalizing offending
motorcyclists could also reduce the frequency of law violations such as not
wearing helmet or riding without motorcycle license, which in turn, would result
into a reduction in the fatality risk of motorcycle crashes.
PMID- 26420218
TI - Albumin in chronic liver disease: structure, functions and therapeutic
implications.
AB - Human serum albumin is a critical plasma protein produced by the liver with a
number of accepted clinical indications in chronic liver disease including
management of circulatory and renal dysfunction in patients with ascites.
Advanced cirrhosis is characterised by reduced albumin concentration as well as
impaired albumin function as a result of specific structural changes and
oxidative damage. Traditionally, the biologic and therapeutic role of albumin in
liver disease was attributed to its oncotic effects but it is now understood that
albumin has a wide range of other important physiologic functions such as
immunomodulation, endothelial stabilisation, antioxidant effects and binding
multiple drugs, toxins and other molecules. This review discusses the
multifunctional properties of albumin and, in particular, the biologic and
clinical implications of structural and functional changes of albumin that are
associated with cirrhosis. Based on these insights, we explore the current and
potential future therapeutic uses of albumin in liver disease.
PMID- 26420219
TI - Determining exon connectivity in complex mRNAs by nanopore sequencing.
AB - Short-read high-throughput RNA sequencing, though powerful, is limited in its
ability to directly measure exon connectivity in mRNAs that contain multiple
alternative exons located farther apart than the maximum read length. Here, we
use the Oxford Nanopore MinION sequencer to identify 7,899 'full-length' isoforms
expressed from four Drosophila genes, Dscam1, MRP, Mhc, and Rdl. These results
demonstrate that nanopore sequencing can be used to deconvolute individual
isoforms and that it has the potential to be a powerful method for comprehensive
transcriptome characterization.
PMID- 26420221
TI - 25OHD analogues and vacuum blood collection tubes dramatically affect the
accuracy of automated immunoassays.
AB - Variations in vitamin D quantification methods are large, and influences of
vitamin D analogues and blood collection methods have not been systematically
examined. We evaluated the effects of vitamin D analogues 25OHD2 and 3-epi 25OHD3
and blood collection methods on vitamin D measurement, using five immunoassay
systems and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum
samples (332) were selected from routine vitamin D assay requests, including
samples with or without 25OHD2 or 3-epi 25OHD3, and analysed using various
immunoassay systems. In samples with no 25OHD2 or 3-epi 25OHD3, all immunoassays
correlated well with LC-MS/MS. However, the Siemens system produced a large
positive mean bias of 12.5 ng/mL and a poor Kappa value when using tubes with
clot activator and gel separator. When 25OHD2 or 3-epi 25OHD3 was present,
correlations and clinical agreement decreased for all immunoassays. Serum 25OHD
in VACUETTE tubes with gel and clot activator, as measured by the Siemens system,
produced significantly higher values than did samples collected in VACUETTE tubes
with no additives. Bias decreased and clinical agreement improved significantly
when using tubes with no additives. In conclusion, most automated immunoassays
showed acceptable correlation and agreement with LC-MS/MS; however, 25OHD
analogues and blood collection tubes dramatically affected accuracy.
PMID- 26420220
TI - Pre-differentiation of human neural stem cells into GABAergic neurons prior to
transplant results in greater repopulation of the damaged brain and accelerates
functional recovery after transient ischemic stroke.
AB - INTRODUCTION: Despite attempts to prevent brain injury during the hyperacute
phase of stroke, most sufferers end up with significant neuronal loss and
functional deficits. The use of cell-based therapies to recover the injured brain
offers new hope. In the current study, we employed human neural stem cells
(hNSCs) isolated from subventricular zone (SVZ), and directed their
differentiation into GABAergic neurons followed by transplantation to ischemic
brain. METHODS: Pre-differentiated GABAergic neurons, undifferentiated SVZ-hNSCs
or media alone were stereotaxically transplanted into the rat brain (n=7/group) 7
days after endothelin-1 induced stroke. Neurological outcome was assessed by
neurological deficit scores and the cylinder test. Transplanted cell survival,
cellular phenotype and maturation were assessed using immunohistochemistry and
confocal microscopy. RESULTS: Behavioral assessments revealed accelerated
improvements in motor function 7 days post-transplant in rats treated with pre
differentiated GABAergic cells in comparison to media alone and undifferentiated
hNSC treated groups. Histopathology 28 days-post transplant indicated that pre
differentiated cells maintained their GABAergic neuronal phenotype, showed
evidence of synaptogenesis and up-regulated expression of both GABA and calcium
signaling proteins associated with neurotransmission. Rats treated with pre
differentiated cells also showed increased neurogenic activity within the SVZ at
28 days, suggesting an additional trophic role of these GABAergic cells. In
contrast, undifferentiated SVZ-hNSCs predominantly differentiated into GFAP
positive astrocytes and appeared to be incorporated into the glial scar.
CONCLUSION: Our study is the first to show enhanced exogenous repopulation of a
neuronal phenotype after stroke using techniques aimed at GABAergic cell
induction prior to delivery that resulted in accelerated and improved functional
recovery.
PMID- 26420222
TI - Smoking behaviors before and after implementation of a smoke-free legislation in
Guangzhou, China.
AB - BACKGROUND: According to the partial smoke-free legislation implemented on 1
September 2010 in Guangzhou, China, smoke-free did not cover all indoor areas.
Some places have a full smoking ban (100 % smoke-free), other places have a
partial smoking ban, and homes have no ban. This study aimed to compare the
smoking behaviors before and after implementation of a smoke-free legislation.
METHOD: A repeated cross-sectional survey was conducted on smoking-related
behaviors with a total of 4,900 respondents before, and 5,135 respondents after
the legislation was instituted. For each wave of the survey, a three-stage
stratified sampling process was used to obtain a representative sample. Pearson's
Chi-square test was used to determine differences of smoking prevalence and quit
ratio between the two samples. Logistic regression models were used to examine
the associations of a smoke-free legislation with smoking behaviors. RESULTS: The
overall daily smoking rate declined significantly from 20.8 % to 18.2 % (p <
0.05), especially among those aged 15-24 years. The quit ratios increased
significantly (from 14.5 % to 17.9 %), but remained low among 15-44 year olds.
The overall self-reported smoking behaviors in locations with a full smoking ban
decreased significantly from 36.4 % to 24.3 % with the greater drops occurring in
cultural venues, public transport vehicles, and government offices. Smoking in
places with partial smoking bans remained high (89.6 % vs. 90.4 %), although a
slight decrease was observed in some of these areas. The implementation of a
smoke-free legislation did not lead to more smoking in homes (91.0 % vs 89.4 %),
but smoking in homes remained high. CONCLUSIONS: These findings highlight the
urgent need for a comprehensive smoke-free legislation covering all public places
in Guangzhou, simultaneously educational interventions and campaigns promoting
voluntary changes in home smoking need to occur.
PMID- 26420223
TI - Nurses' documentation of physiological observations in three acute care settings.
AB - AIMS AND OBJECTIVES: To explore nurses' documentation of physiological
observations in acute care; emergency department, medical and surgical units.
BACKGROUND: In Australia, physiological observations include respiratory rate,
oxygen saturation, heart rate, blood pressure, temperature and level of
consciousness. There is a clear relationship between abnormal physiological
observations and adverse events. Nurses have highest level of responsibility for
accurate measurement, interpretation and documentation of physiological
observations. DESIGN: A descriptive exploratory design was used and the study
data were collected using a prospective point prevalence approach between 25 July
2012-22 August 2012. METHODS: The study was conducted in the emergency
department, two 30-bed medical units and one 30-bed surgical unit of a 578 bed
public health service in Melbourne, Australia. All adult patients aged >=18 years
present during data collection periods were eligible for inclusion. Patients in
the emergency department resuscitation area were excluded. Patient
characteristics and physiological observations for the preceding 24 hours in ward
patients or eight hours in emergency department patients were collected. RESULTS:
One hundred and seventy-eight patients were included; 38 emergency department
patients, 84 medical patients and 56 surgical patients. The median age was 72.5
years and 43.8% were males. The most frequently documented physiological
observations were respiratory rate, oxygen saturation, heart rate and systolic
blood pressure. The least frequently recorded physiological observations were
temperature and conscious state. One or more abnormal physiological parameters
was documented in 79.8% (n = 142) patients; evidence of reporting abnormalities
was documented in 19.7% of patients (n = 28/142). When controlled for length of
stay, physiological observations were more frequently documented in the emergency
department. CONCLUSIONS: There was variability in the number of parameters
documented and frequency of physiological observations documented by nurses.
RELEVANCE TO CLINICAL PRACTICE: Physiological abnormalities that do not
necessarily fulfil rapid response team activation criteria are common in acute
care patients and provide nurses with an opportunity for early recognition of
deteriorating patients.
PMID- 26420224
TI - Genome-wide mRNA-seq profiling reveals predominant down-regulation of lipid
metabolic processes in adipose tissues of Small Tail Han than Dorset sheep.
AB - Small Tail Han and Dorset sheep are two different sheep with distinguished
morphologies in fat depositions. In order to characterize their gene expression
profiles, our present study took the advantages of RNA sequencing technology with
the aims to identify important genes regulating the metabolisms in adipose
tissues of two different sheep. In obtained high quality sequencing reads, 85.9
(Han) and 86.1% (Dorset) were uniquely aligned to Oar v3.1 sheep reference
genome, and over 76% of bases in mapped reads corresponded to mRNA. Using R
package EBSeq, we identified 602 differentially expressed genes. Using the 602
genes, GO analysis showed that 30 out of 56 significantly enriched biological
processes were metabolism related, of which the most significant one was
triglyceride biosynthetic process. The KEGG pathway analysis indicated the down
regulation of several fat metabolic pathways. The predominant down-regulation of
massive metabolic processes, particularly the lipid metabolism, in adipose
tissues of Han sheep could explain, at least in part, the distinguished fat
deposition between two different sheep, and our data constitute a basic picture
of transcriptomes in these sheep for better understanding of underline biological
mechanism in their lipid metabolisms.
PMID- 26420225
TI - Comment on Lerchl study: "Tumor promotion in mice by exposure to radiofrequency
electromagnetic fields still waiting evidence".
PMID- 26420226
TI - Identification and proteomic analysis of osteoblast-derived exosomes.
AB - Exosomes are nanometer-sized vesicles with the function of intercellular
communication, and they are released by various cell types. To reveal the
knowledge about the exosomes from osteoblast, and explore the potential functions
of osteogenesis, we isolated microvesicles from supernatants of mouse Mc3t3 by
ultracentrifugation, characterized exosomes by electron microscopy and
immunoblotting and presented the protein profile by proteomic analysis. The
result demonstrated that microvesicles were between 30 and 100 nm in diameter,
round shape with cup-like concavity and expressed exosomal marker tumor
susceptibility gene (TSG) 101 and flotillin (Flot) 1. We identified a total
number of 1069 proteins among which 786 proteins overlap with ExoCarta database.
Gene Oncology analysis indicated that exosomes mostly derived from plasma
membrane and mainly involved in protein localization and intracellular signaling.
The Ingenuity Pathway Analysis showed pathways are mostly involved in exosome
biogenesis, formation, uptake and osteogenesis. Among the pathways, eukaryotic
initiation factor 2 pathways played an important role in osteogenesis. Our study
identified osteoblast-derived exosomes, unveiled the content of them, presented
potential osteogenesis-related proteins and pathways and provided a rich
proteomics data resource that will be valuable for further studies of the
functions of individual proteins in bone diseases.
PMID- 26420227
TI - Comment on "Reflex epileptic mechanisms in humans: Lessons about natural
ictogenesis" by Peter Wolf.
PMID- 26420228
TI - Reply to "Comment to 'Reflex epileptic mechanisms in humans: Lessons about
natural ictogenesis' by Peter Wolf" by Stefano Meletti and Anna Elisabetta
Vaudano.
PMID- 26420229
TI - Early warning sign on computed tomography of the head.
PMID- 26420230
TI - Ultrafast switching of an electrochromic device based on layered double
hydroxide/Prussian blue multilayered films.
AB - Electrochromic materials are the most important and essential components in an
electrochromic device. Herein, we fabricated high-performance electrochromic
films based on exfoliated layered double hydroxide (LDH) nanosheets and Prussian
blue (PB) nanoparticles via the layer-by-layer assembly technique. X-ray
diffraction and UV-vis absorption spectroscopy indicate a periodic layered
structure with uniform and regular growth of (LDH/PB)n ultrathin films (UTFs).
The resulting (LDH/PB)n UTF electrodes exhibit electrochromic behavior arising
from the reversible K(+) ion migration into/out of the PB lattice, which induces
a change in the optical properties of the UTFs. Furthermore, an electrochromic
device (ECD) based on the (LDH/PB)n-ITO/0.1 M KCl electrolyte/ITO sandwich
structure displays superior response properties (0.91/1.21 s for
coloration/bleaching), a comparable coloration efficiency (68 cm(2) C(-1)) and
satisfactory optical contrast (45% at 700 nm), in comparison with other inorganic
material-based ECDs reported previously. Therefore, this work presents a facile
and cost-effective strategy to immobilize electrochemically active nanoparticles
in a 2D inorganic matrix for potential application in displays, smart windows and
optoelectronic devices.
PMID- 26420231
TI - The discovery of modular binding domains: building blocks of cell signalling.
AB - Cell signalling - the ability of a cell to process information from the
environment and change its behaviour in response - is a central property of life.
Signalling depends on proteins that are assembled from a toolkit of modular
domains, each of which confers a specific activity or function. The discovery of
modular protein- and lipid-binding domains was a crucial turning point in
understanding the logic and evolution of signalling mechanisms.
PMID- 26420233
TI - Insights in Nanoparticle-Bacterium Interactions: New Frontiers to Bypass
Bacterial Resistance to Antibiotics.
AB - Nanotechnology has been revealed as a fundamental approach for antibiotics
delivery. In this paper, recent findings demonstrating the superiority of
nanocarried-antibiotics over "naked" ones and the ways by which nanoparticles can
help to overwhelm bacterial drug resistance are reviewed. The second part of this
paper sheds light on nanoparticle-bacterium interaction patterns. Finally, key
factors affecting the effectiveness of nanoparticles interactions with bacteria
are discussed.
PMID- 26420232
TI - Targeting Polycomb systems to regulate gene expression: modifications to a
complex story.
AB - Polycomb group proteins are transcriptional repressors that are essential for
normal gene regulation during development. Recent studies suggest that Polycomb
repressive complexes (PRCs) recognize and are recruited to their genomic target
sites through a range of different mechanisms, which involve transcription
factors, CpG island elements and non-coding RNAs. Together with the realization
that the interplay between PRC1 and PRC2 is more intricate than was previously
appreciated, this has increased our understanding of the vertebrate Polycomb
system at the molecular level.
PMID- 26420234
TI - Molecular combing compared to Southern blot for measuring D4Z4 contractions in
FSHD.
AB - We compare molecular combing to Southern blot in the analysis of the
facioscapulohumeral muscular dystrophy type 1 locus (FSHD1) on chromosome 4q35
qter (chr 4q) in genomic DNA specimens sent to a clinical laboratory for FSHD
testing. A de-identified set of 87 genomic DNA specimens determined by Southern
blot as normal (n = 71), abnormal with D4Z4 macrosatellite repeat array
contractions (n = 7), indeterminate (n = 6), borderline (n = 2), or mosaic (n =
1) was independently re-analyzed by molecular combing in a blinded fashion. The
molecular combing results were identical to the Southern blot results in 75 (86%)
of cases. All contractions (n = 7) and mosaics (n = 1) detected by Southern blot
were confirmed by molecular combing. Of the 71 samples with normal Southern blot
results, 67 (94%) had concordant molecular combing results. The four
discrepancies were either mosaic (n = 2), rearranged (n = 1), or borderline by
molecular combing (n = 1). All indeterminate Southern blot results (n = 6) were
resolved by molecular combing as either normal (n = 4), borderline (n = 1), or
rearranged (n = 1). The two borderline Southern blot results showed a D4Z4
contraction on the chr 4qA allele and a normal result by molecular combing.
Molecular combing overcomes a number of technical limitations of Southern blot by
providing direct visualization of D4Z4 macrosatellite repeat arrays on specific
chr 4q and chr 10q alleles and more precise D4Z4 repeat sizing. This study
suggests that molecular combing has superior analytical validity compared to
Southern blot for determining D4Z4 contraction size, detecting mosaicism, and
resolving borderline and indeterminate Southern blot results. Further studies are
needed to establish the clinical validity and diagnostic accuracy of these
findings in FSHD.
PMID- 26420235
TI - Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination
with erlotinib in patients with advanced solid tumors.
AB - PURPOSE: Navitoclax (ABT-263), a novel, oral Bcl-2 inhibitor, enhances the
antitumor effects of chemotherapy in vitro by lowering the apoptotic threshold.
This phase I study (NCT01009073) evaluated the safety, pharmacokinetics, and
preliminary antitumor activity of navitoclax combined with erlotinib in patients
with advanced solid tumors. PATIENTS AND METHODS: An open-label dose escalation
study included an arm evaluating navitoclax combined with erlotinib, which
included a dose escalation cohort and a planned safety expansion cohort. Patients
with documented cancers for whom erlotinib therapy was appropriate received
erlotinib 150 mg orally once daily plus navitoclax 150 mg orally once daily, with
navitoclax dose escalation via a continuous reassessment method model. RESULTS:
Eleven patients were enrolled, including six patients with nonsmall cell lung
cancer. Dose-limiting toxicities, most commonly diarrhea, were observed in 4
patients. Navitoclax dosing remained at 150 mg/day because the maximum tolerated
dose was exceeded at this starting dose. The planned dose escalation did not
occur; no recommended phase II dose (RPTD) was identified, and there was no
safety expansion cohort. The most common treatment-related adverse events were
diarrhea, nausea, vomiting, and decreased appetite. Pharmacokinetic analysis
showed no apparent interactions between co-administered navitoclax and erlotinib.
No objective responses were observed; the disease control rate was 27 % (95 % CI,
6-61 %). CONCLUSION: At the erlotinib and navitoclax doses administered, RPTD was
not reached, but the safety profile of the combination was consistent with data
from monotherapy studies. There were no apparent pharmacokinetic interactions
between erlotinib and navitoclax. Three patients had stable disease.
PMID- 26420236
TI - Risk factors for pegylated liposomal doxorubicin-induced palmar-plantar
erythrodysesthesia over time: assessment of monocyte count and baseline clinical
parameters.
AB - PURPOSE: Pegylated liposomal doxorubicin (PLD) is widely used in relapsing
ovarian carcinoma. Its original formulation is metabolized by the monocyte
macrophage system. One of its main toxicities is the palmoplantar
erythrodysesthesia (PPE) syndrome. To date, no predictive factors of PPE have
been identified. METHODS: Data of patients (pts) treated with PLD between 2005
and 2014 were retrospectively collected. A case-control study was performed,
comparing main baseline clinical and biological characteristics of pts
experiencing PPE and those who did not, after at least three cycles of PLD. A
pilot analysis of blood monocyte subpopulations (classical, intermediate and non
classical) was performed by FACS in selected pts. RESULTS: Among 88 pts treated
with PLD, 28 experienced PPE of any grade (31, 95 % CI 21-41). The first
occurrence of PPE was at first cycle in only 11 % of pts, peaked at cycle 2 (32
%) and represented 57 % of cases after cycle 3. Baseline characteristics of pts
with PPE were compared to 27 control pts who received at least 3 cycles. Older
pts represented 61 % of pts with PPE and 15 % of pts without PPE (p = 0.04 by Chi
square test). Monocyte count and inflammatory parameters were not associated with
PPE. However, the analysis of monocyte subpopulations revealed a large inter
patient variability. CONCLUSION: Contrary to most acute toxicities, PPE occurred
more frequently after several cycles, suggesting a PLD body accumulation through
repeated cycles. PPE was more frequent in pts older than 70 years. Monocyte
subpopulations may have different roles on PLD metabolism and warrant further
studies.
PMID- 26420237
TI - The Urine Marker Test: An Alternative Approach to Supervised Urine Collection for
Doping Control.
AB - BACKGROUND: Urine sample collection for doping control tests is a key component
of the World Anti-Doping Agency's fight against doping in sport. However, a
substantial number of athletes experience difficulty when having to urinate under
supervision. Furthermore, it cannot always be ensured that athletes are actually
delivering their own urine. A method that can be used to alleviate the negative
impact of a supervised urination procedure and which can also identify urine as
coming from a specific athlete is the urine marker test. Monodisperse low
molecular weight polyethylene glycols (PEGs) are given orally prior to urination.
Urine samples can be traced to the donor by analysis of the PEGs previously
given. OBJECTIVE: The objective of this study was to investigate the use of the
urine marker during urine doping control testing. METHODS: Two studies
investigated athletes' acceptance of this new method via two questionnaires (n =
253). Furthermore, a third study (n = 91) investigated whether ingestion of the
marker can identify the urine as coming from a specific person and whether the
marker interferes with the detection of prohibited substances. RESULTS AND
CONCLUSIONS: The results indicate that this new method finds wide acceptance both
from athletes who have only heard about the procedure and those who have actually
tested the new method. Furthermore, the marker, which can identify urine as
coming from a specific person, does not interfere with the detection of
prohibited substances.
PMID- 26420239
TI - Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter
gene expression in Jurkat cells.
AB - A coordinated network of zinc transporters and binding proteins tightly regulate
cellular zinc levels. Canonical responses to zinc availability are thought to be
mediated by changes in gene expression of key zinc transporters. We investigated
the temporal relationships of actual zinc uptake with patterns of gene expression
in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat
cell line. Cellular zinc levels were elevated or reduced with exogenous zinc
sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN),
respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc
uptake within 10 min. After 120 min, the expression of metallothionein (positive
control) increased, as well as the zinc exporter, ZnT1; however, the expression
of zinc importers did not change during this time period. Zinc chelation with
TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10
min. After 120 min, the expression of ZnT1 decreased, while again the expression
of zinc importers did not change. Overall, zinc transporter gene expression
kinetics did not match actual changes in cellular zinc uptake with exogenous zinc
or TPEN treatments. This suggests zinc transporter regulation may be the initial
response to changes in zinc within Jurkat cells.
PMID- 26420238
TI - Dose-Response Relationships of Resistance Training in Healthy Old Adults: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Resistance training (RT) is an intervention frequently used to
improve muscle strength and morphology in old age. However, evidence-based, dose
response relationships regarding specific RT variables (e.g., training period,
frequency, intensity, volume) are unclear in healthy old adults. OBJECTIVES: The
aims of this systematic review and meta-analysis were to determine the general
effects of RT on measures of muscle strength and morphology and to provide dose
response relationships of RT variables through an analysis of randomized
controlled trials (RCTs) that could improve muscle strength and morphology in
healthy old adults. DATA SOURCES: A computerized, systematic literature search
was performed in the electronic databases PubMed, Web of Science, and The
Cochrane Library from January 1984 up to June 2015 to identify all RCTs related
to RT in healthy old adults. STUDY ELIGIBILITY CRITERIA: The initial search
identified 506 studies, with a final yield of 25 studies. Only RCTs that examined
the effects of RT in adults with a mean age of 65 and older were included. The 25
studies quantified at least one measure of muscle strength or morphology and
sufficiently described training variables (e.g., training period, frequency,
volume, intensity). STUDY APPRAISAL AND SYNTHESIS METHODS: We quantified the
overall effects of RT on measures of muscle strength and morphology by computing
weighted between-subject standardized mean differences (SMDbs) between
intervention and control groups. We analyzed the data for the main outcomes of
one-repetition maximum (1RM), maximum voluntary contraction under isometric
conditions (MVC), and muscle morphology (i.e., cross-sectional area or volume or
thickness of muscles) and assessed the methodological study quality by
Physiotherapy Evidence Database (PEDro) scale. Heterogeneity between studies was
assessed using I2 and chi2 statistics. A random effects meta-regression was
calculated to explain the influence of key training variables on the
effectiveness of RT in terms of muscle strength and morphology. For meta
regression, training variables were divided into the following subcategories:
volume, intensity, and rest. In addition to meta-regression, dose-response
relationships were calculated independently for single training variables (e.g.,
training frequency). RESULTS: RT improved muscle strength substantially (mean
SMDbs = 1.57; 25 studies), but had small effects on measures of muscle morphology
(mean SMDbs = 0.42; nine studies). Specifically, RT produced large effects in
both 1RM of upper (mean SMDbs = 1.61; 11 studies) and lower (mean SMDbs = 1.76;
19 studies) extremities and a medium effect in MVC of lower (mean SMDbs = 0.76;
four studies) extremities. Results of the meta-regression revealed that the
variables "training period" (p = 0.04) and "intensity" (p < 0.01) as well as
"total time under tension" (p < 0.01) had significant effects on muscle strength,
with the largest effect sizes for the longest training periods (mean SMDbs =
2.34; 50-53 weeks), intensities of 70-79% of the 1RM (mean SMDbs = 1.89), and
total time under tension of 6.0 s (mean SMDbs = 3.61). A tendency towards
significance was found for rest in between sets (p = 0.06), with 60 s showing the
largest effect on muscle strength (mean SMDbs = 4.68; two studies). We also
determined the independent effects of the remaining training variables on muscle
strength. The following independently computed training variables are most
effective in improving measures of muscle strength: a training frequency of two
sessions per week (mean SMDbs = 2.13), a training volume of two to three sets per
exercise (mean SMDbs = 2.99), seven to nine repetitions per set (mean SMDbs =
1.98), and a rest of 4.0 s between repetitions (SMDbs = 3.72). With regard to
measures of muscle morphology, the small number of identified studies allowed us
to calculate meta-regression for the subcategory training volume only. No single
training volume variable significantly predicted RT effects on measures of muscle
morphology. Additional training variables were independently computed to detect
the largest effect for the single training variable. A training period of 50-53
weeks, a training frequency of three sessions per week, a training volume of two
to three sets per exercise, seven to nine repetitions per set, a training
intensity from 51 to 69% of the 1RM, a total time under tension of 6.0 s, a rest
of 120 s between sets, and a rest of 2.5 s between repetitions turned out to be
most effective. LIMITATIONS: The current results must be interpreted with caution
because of the poor overall methodological study quality (mean PEDro score 4.6
points) and the considerable large heterogeneity (I2) = 80%, chi2 = 163.1, df =
32, p < 0.01) for muscle strength. In terms of muscle morphology, our search
identified nine studies only, which is why we consider our findings preliminary.
While we were able to determine a dose-response relationship based on specific
individual training variables with respect to muscle strength and morphology, it
was not possible to ascertain any potential interactions between these variables.
We recognize the limitation that the results may not represent one general dose
response relationship. CONCLUSIONS: This systematic literature review and meta
analysis confirmed the effectiveness of RT on specific measures of upper and
lower extremity muscle strength and muscle morphology in healthy old adults. In
addition, we were able to extract dose-response relationships for key training
variables (i.e., volume, intensity, rest), informing clinicians and practitioners
to design effective RTs for muscle strength and morphology. Training period,
intensity, time under tension, and rest in between sets play an important role in
improving muscle strength and morphology and should be implemented in exercise
training programs targeting healthy old adults. Still, further research is needed
to reveal optimal dose-response relationships following RT in healthy as well as
mobility limited and/or frail old adults.
PMID- 26420240
TI - Does addition of low-level laser therapy (LLLT) in conservative care of knee
arthritis successfully postpone the need for joint replacement?
AB - The current study evaluates whether the addition of low-level laser therapy into
standard conventional physical therapy in elderly with bilateral symptomatic tri
compartmental knee arthritis can successfully postpone the need for joint
replacement surgery. A prospective randomized cohort study of 100 consecutive
unselected elderly patients with bilateral symptomatic knee arthritis with each
knee randomized to receive either treatment protocol A consisting of conventional
physical therapy or protocol B which is the same as protocol A with added low
level laser therapy. The mean follow-up was 6 years. Treatment failure was
defined as breakthrough pain which necessitated joint replacement surgery. After
a follow-up of 6 years, patients clearly benefited from treatment with protocol B
as only one knee needed joint replacement surgery, while nine patients treated
with protocol A needed surgery (p < 0.05). We conclude low-level laser therapy
should be incorporated into standard conservative treatment protocol for
symptomatic knee arthritis.
PMID- 26420241
TI - Extended minimally invasive lung resections: VATS bilobectomy, bronchoplasty, and
pneumonectomy.
AB - PURPOSE: The aim of the present study was to analyze feasibility, morbidity,
mortality, and oncologic outcome of extended video-assisted thoracoscopic surgery
(VATS) anatomic lung resections in a single-center experience. Extended
resections include bilobectomies, bronchoplasties, and pneumonectomies. METHODS:
The present study is a retrospective analysis of a prospectively maintained
institutional database. Between 2009 and 2014, 390 patients were scheduled for
anatomical VATS resections. VATS resection was completed in 370 patients giving
an overall conversion rate of 5.1 %. Extended VATS resections were performed in
29 patients (7.8 %): bilobectomy in 8, bronchoplastic resection in 15 (2
bronchial sleeve resections, 11 wedge bronchoplasties, 2 simple bronchoplasties),
and pneumonectomy in 6. RESULTS: Median operative time was 217 min (117-390 min).
Median chest tube duration was 4 days (range, 2-50 days). Median length of
hospital stay was 9 days (6-63 days). There was no in-hospital mortality. Major
complications with need for reinterventions occurred in three patients (10.3 %):
one air leakage from bronchial stump after pneumonectomy, one hematothorax after
completion pneumonectomy, and one chylothorax. All complications were treated
with VATS procedures. Minor complications included two persistent air leaks that
were treated with an additional chest drain and resolved, one urinary tract
infection, one atelectasis with need for bronchoscopy, and one pleural fluid
collection with the need for drainage. After a median follow-up of 26 months, no
local tumor recurrence occurred. Two patients had a second lung primary cancer
and four patients with advanced tumor stages had distant recurrent disease.
CONCLUSIONS: With growing experience, extended VATS resections are feasible in
selected cases with low perioperative morbidity and mortality.
PMID- 26420242
TI - The lower effectiveness of text-only health warnings in China compared to
pictorial health warnings in Malaysia.
AB - BACKGROUND: In 2009, China changed its health warnings on cigarette packs from
side-only text warnings to two text-only warnings on 30% of the bottom of the
front and back of the pack. Also in 2009, Malaysia changed from similar text
warnings to pictorial health warnings consistent with Framework Convention on
Tobacco Control (FCTC) Article 11 Guidelines. OBJECTIVE: To measure the impact of
the change in health warnings in China and to compare the text-only health
warnings to the impact of the pictorial health warnings introduced in Malaysia.
METHODS: We measured changes in key indicators of warning effectiveness among a
longitudinal cohort sample of smokers from Waves 1 to 3 (2006-2009) of the
International Tobacco Control (ITC) China Survey and from Waves 3 to 4 (2008
2009) of the ITC Malaysia Survey. Each cohort consisted of representative samples
of adult (>=18 years) smokers from six cities in China (n=6575) and from a
national sample in Malaysia (n=2883). Generalised Estimating Equations (GEE) were
used to examine the impact of the health warnings on subsequent changes in
salience of warnings, cognitive and behavioural outcomes. FINDINGS: Compared to
Malaysia, the weak text-only warning labels in China led to a significant change
in only two of six key indicators of health warning effectiveness: forgoing
cigarettes and reading the warning labels. The change to pictorial health
warnings in Malaysia led to significant and substantial increases in five of six
indicators (noticing, reading, forgoing, avoiding, thinking about quitting).
CONCLUSIONS: The delay in implementing pictorial health warnings in China
constitutes a lost opportunity for increasing knowledge and awareness of the
harms of cigarettes, and for motivating smokers to quit.
PMID- 26420243
TI - Predomination of IL-17-producing tryptase-positive/chymase-positive mast cells in
azoospermic chronic testicular inflammation.
AB - Chronic testicular inflammation and infection have been regarded as important
factors in the pathogenesis of azoospermia. As key effector cells in innate and
adaptive immune system, mast cells (MCs) were observed in inflammation and
autoimmune disease. Furthermore, increased expression of tryptase-positive MCs
has been reported in testicular disorders associated with male
infertility/subfertility. However, little is known about the potential
relationship between MCs and chronic testicular inflammation in azoospermic
patients. Moreover, the preferential expression of MCs' subtypes in testis of
these patients is still far from being understood. Thus, this study aimed to
investigate characteristics of testicular MCs as well as their subtypes in
azoospermic men with chronic testicular inflammation (AZI, n = 5) by
immunohistochemical techniques. Our results showed significant increase of MCs in
AZI, and more importantly, considerable numbers of tryptase-positive/chymase
positive MCs could also be demonstrated in AZI, when compared to control groups
representing azoospermia without chronic testicular inflammation (AZW, n = 5) and
normal spermatogenesis (NT, n = 5) respectively. Most interestingly,
immunofluorescence staining revealed autoimmune-associated interleukin (IL)-17
producing MCs in AZI, whereas co-expression of MC markers with tumour necrosis
factor (TNF)-alpha, IL-10 and IL-1beta could not be detected. In conclusion, AZI
is associated with significant increase of tryptase-positive/chymase-positive MCs
expressing IL-17, and these MCs might contribute to the pathogenesis of AZI.
PMID- 26420245
TI - Assessment of health-related quality of life of Bangladeshi patients with type 2
diabetes using the EQ-5D: a cross-sectional study.
AB - BACKGROUND: The management of diabetes requires a fundamental change in the
lifestyle of patients, and one of the important outcome criteria is the quality
of life. We assessed the health-related quality of life (HR-QoL) and examined the
factors associated with it in type 2 diabetes. METHODS: An analytical cross
sectional study was conducted among 500 type 2 diabetes patients (age >25 years
and duration of diabetes >1 year). They were selected conveniently from the Out
Patient department of the Bangladesh Institute of Health Sciences Hospital. The
HR-QoL was assessed using an adapted and validated Bangla version of the EQ-5D
((c) 1990 EuroQol Group. EQ-5DTM) questionnaire. It has five domains: mobility,
self-care, usual activities, pain/discomfort, and anxiety/depression and two
levels (problem and no problem) on each dimension. The responses to the EQ-5D
were further translated into a single summary EQ-5D index using the UK TTO value
set. RESULTS: Of the patients, 50.2% were female, and 49.4% were aged >55 years.
Only 28.4% had completed higher secondary education, and 50.8% were from lower
middle-income families. Around 78.8% either had overweight or were obese. About
50.4% had problems in mobility, 28.2% in self-care, 47.6% in usual activities,
72.8% in pain/discomfort, and 73.6% in anxiety/depression. Results of binary
logistic regression analysis showed that age, gender, lower-middle income, and
HbA1C were significantly (p < 0.05) associated with mobility. Self-care was
significantly (p < 0.05) related to age, family history and duration of diabetes
mellitus (DM). Gender, family history of DM, and lower-middle income had a
significant (p < 0.05) association with usual activities. Pain was significantly
(p < 0.05) associated with age, lower-middle income, and upper-middle income.
Rural area, higher education, and HbA1C were significantly (p < 0.05) related to
anxiety. Results of multiple linear regression analysis showed that age (p =
0.0001), female gender (p = 0.0001), and prescribed treatment (p = 0.048) were
associated with the EQ-5D index. CONCLUSIONS: The large majority (73%) of the
patients had problems in pain/discomfort and anxiety/depression; 50% had problems
in mobility and usual activities; and three in ten in self-care. Age, female
gender, income, education, family history and duration of DM, and prescribed
treatment are important factors that are associated with the HR-QoL in type 2
diabetes.
PMID- 26420244
TI - Perception of quality of care of patients with potentially severe diseases
evaluated at a distinct quick diagnostic delivery model: a cross-sectional study.
AB - BACKGROUND: Although hospital-based outpatient quick diagnosis units (QDU) are an
increasingly recognized cost-effective alternative to hospitalization for the
diagnosis of potentially serious diseases, patient perception of their quality of
care has not been evaluated well enough. This cross-sectional study analyzed the
perceived quality of care of a QDU of a public third-level university hospital in
Barcelona. METHODS: One hundred sixty-two consecutive patients aged >= 18 years
attending the QDU over a 9-month period were invited to participate. A validated
questionnaire distributed by the QDU attending physician and completed at the end
of the first and last QDU visit evaluated perceived quality of care using six
subscales. RESULTS: Response rate was 98 %. Perceived care in all subscales was
high. Waiting times were rated as 'short'/'very short' or 'better'/'much better'
than expected by 69-89 % of respondents and physical environment as
'better'/'much better' than expected by 94-96 %. As to accessibility, only 3 %
reported not finding the Unit easily and 7 % said that frequent travels to
hospital for visits and investigations were uncomfortable. Perception of patient
physician encounter was high, with 90-94 % choosing the positive extreme ends of
the clinical information and personal interaction subscales items. Mean score of
willingness to recommend the Unit using an analogue scale where 0 was 'never' and
10 'without a doubt' was 9.5 (0.70). On multivariate linear regression, age >65
years was an independent predictor of clinical information, personal interaction,
and recommendation, while age 18-44 years was associated with lower scores in
these subscales. No schooling predicted higher clinical information and
recommendation scores, while university education had remarkable negative
influence on them. Having >=4 QDU visits was associated with lower time to
diagnosis and recommendation scores and malignancy was a negative predictor of
time to diagnosis, clinical information, and recommendation. DISCUSSION: It is
worthy of note that the questionnaire evaluated patient perception and opinions
of healthcare quality including recommendation rather than simply satisfaction.
It has been argued that perception of quality of care is a more valuable approach
than satisfaction. In addition to embracing an affective dimension, satisfaction
appears more dependent on patient expectations than is perception of quality.
CONCLUSIONS: While appreciating that completing the questionnaire immediately
after the visit and its distribution by the QDU physician may have affected the
results, scores of perceived quality of care including recommendation were high.
There were, however, significant differences in several subscales associated with
age, education, number of QDU visits, and diagnosis of malignant vs. benign
condition.
PMID- 26420246
TI - Left anterior small thoracotomy for minimally invasive coronary artery bypass
grafting.
AB - Since the 1990 s, minimally invasive cardiac surgery has gained wide acceptance
due to patient and economic demand. The advantages are less trauma, bleeding,
wound infections, pain and faster recovery. Many studies showed that the outcomes
are comparable with those of conventional sternotomy. Left anterior small
thoracotomy (LAST) evolved into a routine and safe access in specialized centres
for minimally invasive direct coronary artery bypass grafting. The 6-cm incision
is localized above the fourth intercostal space, 3-4 cm lateral to the left
sternal border and below the left mammilla. With a double-lumen tube, the left
lung is deflated before entering the pleural space. The left internal mammary
artery is harvested under direct vision with the use of special retractors. The
anastomosis of the left anterior descending artery is performed on the beating
heart as known from off-pump surgery. One chest tube is inserted. The intercostal
space is closed with braided sutures to prevent lung herniation. Ropivacaine is
used for local infiltration. The pectoral muscle, subcutaneous tissue and skin
are closed with running sutures. Complications of the LAST approach are rare
(conversion to sternotomy, re-thoracotomy, phrenic nerve palsy, wound infection
and thoracic wall hernia) and well manageable.
PMID- 26420247
TI - Carotid artery cannulation in aortic surgery: why not?
PMID- 26420248
TI - Effect of orthodontic brackets and different wires on radiofrequency heating and
magnetic field interactions during 3.0-T MRI: Author response.
PMID- 26420250
TI - Gastric-Type Extremely Well-Differentiated Adenocarcinoma of the Stomach: A
Challenge for Preoperative Diagnosis.
AB - Gastric-type extremely well-differentiated adenocarcinoma (EWDA) is a rare type
of gastric adenocarcinoma characterized by infiltration of well-formed mucinous
glands with little or no nuclear atypia, which resemble foveolar epithelium or
pyloric glands. Because of its high degree of differentiation, preoperative
biopsy diagnosis of gastric-type EWDA is very difficult. We encountered a case of
gastric-type EWDA, manifesting as a Borrmann type 4 lesion, in a 47-year-old man.
Despite four repeated biopsies, the preoperative biopsy diagnosis was not
conclusive due to the scarcity of diagnostic tumor cells and lack of knowledge
regarding the unusual histologic findings of gastric-type EWDA. We herein
describe the histologic findings of gastric-type EWDA in detail, with the aim of
facilitating a preoperative biopsy diagnosis and understanding of this rare type
of gastric adenocarcinoma.
PMID- 26420249
TI - Reproducibility of brain metabolite concentration measurements in lesion free
white matter at 1.5 T.
AB - BACKGROUND: Post processing for brain spectra has a great influence on the fit
quality of individual spectra, as well as on the reproducibility of results from
comparable spectra. This investigation used pairs of spectra, identical in system
parameters, position and time assumed to differ only in noise. The metabolite
amplitudes of fitted time domain spectroscopic data were tested on
reproducibility for the main brain metabolites. METHODS: Proton spectra of white
matter brain tissue were acquired with a short spin echo time of 30 ms and a
moderate repetition time of 1500 ms at 1.5 T. The pairs were investigated with
one time domain post-processing algorithm using different parameters. The number
of metabolites, the use of prior knowledge, base line parameters and common or
individual damping were varied to evaluate the best reproducibility. RESULTS: The
protocols with most reproducible amplitudes for N-acetylaspartate, creatine,
choline, myo-inositol and the combined Glx line of glutamate and glutamine in
lesion free white matter have the following common features: common damping of
the main metabolites, a baseline using only the points of the first 10 ms, no
additional lipid/macromolecule lines and Glx is taken as the sum of separately
fitted glutamate and glutamine. This parameter set is different to the one
delivering the best individual fit results. DISCUSSION: All spectra were acquired
in "lesion free" (no lesion signs found in MR imaging) white matter. Spectra of
brain lesions, for example tumors, can be drastically different. Thus the results
are limited to lesion free brain tissue. Nevertheless the application to studies
is broad, because small alterations in brain biochemistry of lesion free areas
had been detected nearby tumors, in patients with multiple sclerosis, drug abuse
or psychiatric disorders. CONCLUSION: Main metabolite amplitudes inside healthy
brain can be quantified with a normalized root mean square deviation around 5 %
using CH3 of creatine as reference. Only the reproducibility of myo-inositol is
roughly twice as bad. The reproducibility should be similar using other
references like internal or external water for an absolute concentration
evaluation and are not influenced by relaxation corrections with literature
values.
PMID- 26420251
TI - IgG4-Related Disease Presented as a Mural Mass in the Stomach.
AB - Isolated gastric IgG4-related disease (IgG4-RD) is a very rare tumefactive
inflammatory condition, with only a few cases reported to date. A 48-year-old
woman was incidentally found to have a subepithelial tumor in the stomach. Given
a presumptive diagnosis of gastrointestinal stromal tumor or neuroendocrine
tumor, she underwent wedge resection. The lesion was vaguely nodular and mainly
involved the submucosa and proper muscle layer. Microscopically, all classical
features of type I autoimmune pancreatitis including lymphoplasmacytic
infiltration, storiform fibrosis, obliterative phlebitis, and numerous IgG4
positive plasma cells were seen. She had no evidence of IgG4-RD in other organs.
Although very rare, IgG4-RD should be considered one of the differential
diagnoses in the setting of gastric wall thickening or subepithelial mass-like
lesion. Deep biopsy with awareness of this entity might avoid unnecessary
surgical intervention.
PMID- 26420252
TI - CD30-Positive T-Cell Lymphoproliferative Disease of the Oral Mucosa in Children:
A Manifestation of Epstein-Barr Virus-Associated T-Lymphoproliferative Disorder.
AB - Eosinophilic ulcer of the oral mucosa (EUOM) is a very rare, benign, self
limiting ulcerative lesion of the oral cavity of unknown pathogenesis, and
belongs to the same spectrum of CD30(+) T-cell lymphoproliferative disease (LPD)
of the oral mucosa. The etiology and pathogenesis of the disease are unknown. We
report two cases in children who were initially diagnosed with EUOM and CD30(+) T
cell LPD, respectively. However, retrospective analysis revealed that a majority
of infiltrated atypical T cells were positive for Epstein-Barr virus (EBV). The
present cases suggest that the pathogenesis and etiology of EUOM or CD30(+) T
cell LPD occurring in children are different from those in adults. EUOM or
CD30(+) T-cell LPD in children is a manifestation of EBV-positive T-cell LPD, and
should therefore be distinguished from the disease in adults.
PMID- 26420253
TI - Serum angiopoietin-like protein 2 as a potential biomarker for diagnosis, early
recurrence and prognosis in gastric cancer patients.
AB - Chronic inflammation of gastric mucosa by Helicobacter pylori infection can
initiate gastric carcinogenesis. As angiopoietin-like protein 2 (ANGPTL2)
mediates inflammation and inflammation-associated carcinogenesis, we investigated
the functional and clinical significance of ANGPTL2 in human gastric cancer (GC).
SiRNA knockdown studies were performed for the functional assessment of ANGPTL2
in GC cell lines. ANGPTL2 expression was evaluated immunohistochemically in 192
tissue specimens from GC patients. In addition, we screened serum ANGPTL2 levels
from 32 GC patients and 23 healthy controls; and validated these results in 194
serum samples from GC patients and 45 healthy controls by ELISA. ANGPTL2
knockdown caused anoikis and inhibited proliferation, invasion and migration in
GC cells. ANGPTL2 expression was upregulated in GC tissues compared to normal
gastric mucosa; and high ANGPTL2 expression was significantly associated with
tumor progression, early recurrence (P = 0.003) and poor prognosis (P = 0.007).
Serum ANGPTL2 in GC patients was significantly higher than for healthy controls
(P < 0.05), and accurately distinguished GC patients from healthy control (AUC =
0.865). The validation step confirmed significantly higher serum ANGPTL2 levels
in GC patients than healthy controls (P < 0.0001). Receiver operating
characteristic curves yielded robust AUC value (0.831) accompanied by high
sensitivity (73.0%) and specificity (82.2%) in distinguishing GC patients from
healthy controls. High serum ANGPTL2, rather than its expression in matched
tissues, was significantly associated with tumor progression, and emerged as an
independent marker for recurrence (HR: 5.05, P = 0.0004) and prognosis (HR: 3.6,
P = 0.01). Serum ANGPTL2 expression is a potential noninvasive biomarker for
diagnosis, early recurrence and prognosis of GC patients.
PMID- 26420254
TI - Pan-genomic analysis to redefine species and subspecies based on quantum
discontinuous variation: the Klebsiella paradigm.
AB - BACKGROUND: Various methods are currently used to define species and are based on
the phylogenetic marker 16S ribosomal RNA gene sequence, DNA-DNA hybridization
and DNA GC content. However, these are restricted genetic tools and showed
significant limitations. RESULTS: In this work, we describe an alternative method
to build taxonomy by analyzing the pan-genome composition of different species of
the Klebsiella genus. Klebsiella species are Gram-negative bacilli belonging to
the large Enterobacteriaceae family. Interestingly, when comparing the core/pan
genome ratio; we found a clear discontinuous variation that can define a new
species. CONCLUSIONS: Using this pan-genomic approach, we showed that Klebsiella
pneumoniae subsp. ozaenae and Klebsiella pneumoniae subsp. rhinoscleromatis are
species of the Klebsiella genus, rather than subspecies of Klebsiella pneumoniae.
This pan-genomic analysis, helped to develop a new tool for defining species
introducing a quantic perspective for taxonomy.
PMID- 26420255
TI - Uveitis in Children: Diagnosis and Management.
AB - Uveitis is a term used to describe inflammation of uvea, which is the middle
layer of eye. It is an important cause of blindness in children in both developed
and developing countries. Delayed diagnosis, inadequate treatment and risk of
amblyopia are some of the factors that are unique to childhood uveitis and are
responsible for significant morbidity seen with this disease.
PMID- 26420257
TI - Cutting science budget would be "Neanderthal" behaviour, expert says.
PMID- 26420256
TI - Changes in PH in exhaled breath condensate after specific bronchial challenge
test in patients with chronic hypersensitivity pneumonitis: a prospective study.
AB - BACKGROUND: The aim of this study was to investigate the influence of the
specific inhalation challenge (SIC) on changes of pH values in exhaled breath
condensate (EBC) in patients with hypersensitivity pneumonitis (HP). METHODS: A
prospective study of 85 patients with suspected HP, of whom 63 were diagnosed
with HP due to exposure to avian or fungal antigens. In all cases, EBC samples
were collected before and after completion of the SIC and pH values were
determined. RESULTS: Taken as a whole, patients with HP did not present changes
in EBC pH after SIC. However, considering only patients with exposure to molds,
those diagnosed with HP had a significantly more acid pH post-SIC than those with
another diagnosis (p = 0.011). This fact is not observed in patients exposed to
bird's antigens. A ROC curve showed that a reduction in EBC pH of 0.3 units or
more after SIC in patients diagnosed with HP due to exposure to molds had a
sensitivity of 30 % (CI: 12.8 to 54.3 %) and a specificity of 100 % (CI: 65.5 to
100 %). CONCLUSION: EBC pH may be useful in interpreting SIC results in patients
with HP, especially in those patients exposed to molds. Further studies are now
required to test the validity of these proposals.
PMID- 26420258
TI - The region from phenylalanine-28 to lysine-50 of a yeast mitochondrial ATPase
inhibitor (IF1) forms an alpha-helix in solution.
AB - A mitochondrial ATPase inhibitor, IF1, is a 63 amino acid residue protein that
regulates the activity of ATP synthase (F(1)F(o)-ATPase). In the present study,
we constructed mutant IF1 proteins with proline residues inserted into a wide
range of their primary structures to determine the location and function of alpha
helix in the protein. A total of 11 yeast IF1 protein mutants were expressed and
purified. Proline insertions in the region 28-50 reduced alpha-helical contents,
indicating that the region formed a helix in solution. Oligomer formation of
proline mutants at the C-terminal 38-60 region was markedly reduced, indicating
that the region is required for oligomerization of the protein. Proline mutants
at the N-terminal 18-39 region did not inhibit F(1)F(o)-ATPase, indicating that
the region is required for ATPase inhibitory activity. Inhibition of a proline
insertion mutant between residues 44 and 45 that lost a large portion of the
alpha-helix was slower, although the maximal inhibition level of the mutant
protein was comparable to that of wild-type IF1. The results suggest that the
helix of yeast IF1 facilitates binding to F(1) by promoting initial interaction
of the proteins.
PMID- 26420259
TI - Effects of cellulase supplementation to corn soybean meal-based diet on the
performance of sows and their piglets.
AB - A total of 15 primiparous sows (Landrace * Yorkshire) and their litters were used
in the current study to evaluate the efficacy of cellulase supplementation on the
production performance of sows and piglets. Pigs were randomly allocated into one
of three treatments with five replicates per treatment. The dietary treatments
were as follows: (i) CON (corn-soybean meal-based control); (ii) EZ1 (CON + 0.05%
cellulase); and (iii) EZ2 (CON + 0.10% cellulase). The supplementation of
cellulase had no effect (P > 0.05) on body weight and feed intake of lactating
sows. At weaning, back fat thickness loss decreased (P = 0.04) linearly in EZ1
and EZ2 treatments. The average daily gain (ADG) of piglets increased (linear P =
0.06, quadratic P = 0.04)) during days 14 to 21 as well as at days 21 to 25
(linear P = 0.03 and quadratic P = 0.01) with the increase in the level of
supplemented enzyme. Dry matter and nitrogen digestibility increased (linear P =
0.01) in lactating sows fed EZ1 and EZ2 diet compared with CON. In conclusion, it
is suggested that cellulase supplementation to corn-soybean meal based diet
exerts beneficial effects to sows in reducing their back fat thickness loss at
weaning and also helps to improve nutrient digestibility. It also helped to
improve the ADG of piglets.
PMID- 26420260
TI - Cdh2 stabilizes FGFR1 and contributes to primed-state pluripotency in mouse
epiblast stem cells.
AB - The cell adhesion molecule Cadherin 2 (Cdh2) plays important roles in somatic
cell adhesion, proliferation and migration. Cdh2 is also highly expressed in
mouse epiblast stem cells (mEpiSCs), but its function in these cells is unknown.
To understand the function of Cdh2 in mEpiSCs, we compared the expression of
pluripotency-related genes in mEpiSCs and mouse embryonic stem cells (mESCs)
after either Cdh2 knockdown or Cdh2 over-expression. Introduction of specific
siRNA against Cdh2 led to attenuation of pluripotency-related genes. Pluripotent
gene expression was not recovered by over-expression of Cdh1 following Cdh2
knockdown. Western blot analysis and co-immunoprecipitation assays revealed that
Cdh2 stabilizes FGFR1 in mEpiSCs. Furthermore, stable transfection of mESCs with
Cdh2 cDNA followed by FGF2 supplementation accelerated cell differentiation.
Thus, Cdh2 contributes to the establishment and maintenance of FGF signaling
dependent self-renewal in mEpiSCs through stabilization of FGFR1.
PMID- 26420262
TI - Effect of observation on lower limb prosthesis gait biomechanics: Preliminary
results.
AB - BACKGROUND: The Hawthorne effect, a subcategory of reactivity, causes human
behavior to change when under observation. Such an effect may apply to gait
variation of persons with prosthetics or orthotics devices. OBJECTIVES: This
study investigated whether the presence of observers directly affects the gait
pattern of users of lower limb prostheses. STUDY DESIGN: Within-subject
intervention study. METHODS: Primary outcome measures were gait parameters of
initial double support time and upper body lateral tilt angle, which were
collected with a mobile sensor attached to the subjects' back. To make subjects
feel unwatched, a certain amount of deception was necessary, and two different
conditions were created and statistically compared against each other: one in
which the subjects were initially unaware of the attention of observers and
another one in which the same subjects were aware of a group of observers.
RESULTS: Data from two subjects using trans-femoral prosthesis are reported.
Findings included a change in step initial double support percentage by up to
14.2% (p = 0.019). Considerable changes were also noted in secondary outcome
measures including speed, stride length, and stride symmetry. CONCLUSIONS: A
reactivity effect of observation exists in prosthetics gait analysis. More
comprehensive studies may be motivated by these preliminary findings. CLINICAL
RELEVANCE: Results of this study suggest that users of lower limb prostheses walk
differently when their gait is being assessed (e.g. in the prosthetist's office)
than in situations without observers. This may in part explain the clinical
experience that modifications of prosthetic fit or alignment provide only short
term betterment.
PMID- 26420261
TI - Xpert MTB/RIF assay can be used on archived gastric aspirate and induced sputum
samples for sensitive diagnosis of paediatric tuberculosis.
AB - BACKGROUND: Tuberculosis (TB) in children is neglected, mainly due to lack of
sensitive diagnostic tools. Recently Xpert MTB/RIF assay has revolutionized the
diagnostic field, but its usefulness in pediatric TB has not been reported from
India and no report is available on its use on long term archived samples.
METHODS: We recruited 130 pediatric patients with probable intrathoracic
tuberculosis and their gastric aspirate (GA) and induced sputum (IS) samples on 2
consecutive days were collected between January 2009 and December 2012. All
samples (n = 520) were subjected to smear examination, BACTEC-MGIT culture and in
house multiplex PCR. An aliquot of each sample was stored at -80 degrees C and
tested in Xpert MTB/RIF assay in 2013. RESULTS: Sample wise and patient wise
detection rate of smear microscopy was 4.4 % and 10 %, while for BACTEC-MGIT
culture this rate was 24.4 % and 46.9 %, respectively. Of the 130 day 1 GA
samples, 31.5 % and 27.7 % day 2 GA samples were culture positive. Only 17.7 % GA
samples were positive on both days. Of the 130 IS samples collected on day 1 and
day 2, 15.4 % and 23.1 % samples were culture positive. A combination of GA and
IS yielded best results. Combining both GA and IS, the overall sensitivity of
Xpert MTB/RIF on smear and culture positive samples was 95.6 %. In smear negative
and culture positive samples its sensitivity was 62.5 %. The duration of sample
storage impacted the Xpert MTB/RIF test performance (p = 0.0001). In smear
positive samples stored for 650-849 days, its sensitivity was 85.7 % and 77.1 %
for IS and GA samples which dropped to 33.3 % and 50 %, respectively, if stored
for more than 1050 days. DISCUSSION: Confirmatory diagnosis of tuberculosis
particularly in children is a medical challenge. No laboratory or radiological
test can reach to a satisfactory level of diagnostic sensitivity. However, in
this study we found that combination of multiple samples and multiple diagnostic
tests can give much better yield, though not optimum. In present study,
combination of 2 gastric aspirates (GA) and 2 induced sputum (IS) samples
collected on two consecutive days, and tested on three diagnostic methods yielded
a significantly high detection rate. Despite long term storage, the overall
sensitivity of Xpert MTB/RIF on smear and -culture positive samples remained very
high. But after storing these samples under subfreezing conditions the
sensitivity of Xpert MTB/RIF decreased significantly. This is expected because
even if the sample is smear and culture positive, the count of surviving
mycobacteria goes down, after several years this count can reach to a
undetectable level. CONCLUSION: This report shows that smear and culture positive
samples stored at subfreezing conditions for several years can be used in the
Xpert MTB/RIF assay, while maintaining appreciable diagnostic test sensitivity
and specificity.
PMID- 26420263
TI - Prevalence of concomitant hypo-hyperdontia in a group of Turkish orthodontic
patients.
AB - AIM: Was to investigate hypodontia and supernumerary teeth, in the same
individual, which is termed 'concomitant hypo-hyperodontia' (CHH) and the
frequency of CHH in a large sample of non-syndromic orthodontic patients.
METHODS: In this retrospective study, the records were reviewed of 1236 Turkish
orthodontic patients treated between 1994 and 2003 at Marmara University,
Paediatric Clinics. Data were collected and analysed for differences in the
distribution of hypodontia and supernumerary teeth, sex, and malocclusion type.
RESULTS: A total of 1236 orthodontic patients were included in this study. The
mean age of children was 17.05 years (SD = 2.5). The prevalence of hypodontia was
7 % (82) and was more frequently found in girls. Concomitant hypo-hyperodontia
was found in 9 children, involving 8 boys and 1 girl. The frequency of mesiodens
in hypodontia patients with Class I, II, and Class III malocclusions was 3 (3
boys), 5 (5 boys) and 1 (1 girl), respectively. CHH prevalence was found 0.7 % (9
patients). The gender ratio was 0.2:1.1 for CHH. CONCLUSIONS: Supernumerary teeth
may lead to some clinical problems including malocclusions, aesthetic and
functional complaints, and also psychological problems. Early diagnosis of the
condition and multidisciplinary approach for management of such cases is
recommended.
PMID- 26420264
TI - Effect on oral pH changes and taste perception in 10-14-year-old children, after
calcium fortification of a fruit juice.
AB - AIM: The aim was to determine the effect of calcium fortification of a
commercially available mixed-fruit juice on oral pH changes and taste perception
in a group of 10 to 14 year-old Indian children. METHOD: A controlled, blinded,
non-randomised clinical trial was adopted, consisting of a sample of 100 healthy
children (DMFT <3; age 10-14 years), who were exposed to three test juices one by
one [Group A: original fruit juice (control group); Group B: calcium-fortified
fruit juice and Group C: calcium + vitamin D fortified fruit juice]. Oral pH,
collection of saliva and plaque sampling was undertaken, before and after the
juice exposure by each subject at 0, 1, 5, 15, 30 and 45 min. The respective pH
was measured with a digital pH meter. For taste perception, a scoring system was
used after exposure of the juices to the subjects in a blind manner. The
statistical evaluation was done using one-way ANOVA for salivary and plaque pH
and Kruskal-Wallis test for buffer capacity and taste perception. RESULTS: There
was a smaller drop in salivary and plaque pH (p < 0.5) and a significant
reduction in perceived taste (p < 0.001) by the subjects after calcium
modification of fruit juice. CONCLUSION: The calcium-modified mixed fruit juices
was less acidogenic compared with the unfortified juice, and hence will be less
cariogenic and erosive towards teeth.
PMID- 26420265
TI - Eastern equine encephalitis virus in mice I: clinical course and outcome are
dependent on route of exposure.
AB - BACKGROUND: Eastern equine encephalitis virus (EEEV), an arbovirus, is an
important human and veterinary pathogen belonging to one of seven antigenic
complexes in the genus Alphavirus, family Togaviridae. EEEV is considered the
most deadly of the mosquito-borne alphaviruses due to the high case fatality rate
associated with clinical infections, reaching up to 75 % in humans and 90 % in
horses. In patients that survive acute infection, neurologic sequelae are often
devastating. Although natural infections are acquired by mosquito bite, EEEV is
also highly infectious by aerosol. This fact, along with the relative ease of
production and stability of this virus, has led it to being identified as a
potential agent of bioterrorism. METHODS: To characterize the clinical course and
outcome of EEEV strain FL93-939 infection, we compared clinical parameters,
cytokine expression, viremia, and viral titers in numerous tissues of mice
exposed by various routes. Twelve-week-old female BALB/c mice were infected by
the intranasal, aerosol, or subcutaneous route. Mice were monitored for clinical
signs of disease and euthanized at specified time points (6 hpi through 8 dpi).
Blood and tissues were harvested for cytokine analysis and/or viral titer
determination. RESULTS: Although all groups of animals exhibited similar clinical
signs after inoculation, the onset and severity differed. The majority of those
animals exposed by the aerosol route developed severe clinical signs by 4 dpi.
Significant differences were also observed in the viral titers of target tissues,
with virus being detected in the brain at 6 hpi in the aerosol study. CONCLUSION:
The clinical course and outcome of EEEV infection in mice is dependent on route
of exposure. Aerosol exposure to EEEV results in acute onset of clinical signs,
rapid neuroinvasion, and 100 % mortality.
PMID- 26420266
TI - On the Effect of Thermophysical Properties of Clothing on the Heat Strain
Predicted by PHS Model.
AB - Procedures and equations reported in ISO 9920 for the correction of basic
thermophysical clothing properties taking into account pumping effect and air
movement are very different from those used by the Predicted Heat Strain (PHS)
model in ISO 7933. To study the effect of these differences on the assessment of
hot environments using the PHS model, an analysis focusing on the modelling of
the dynamic thermal insulation and the vapour resistance of the clothing reported
in ISO 9920 and ISO 7933 standards will be discussed in this paper. The results
are useful evidence to start a discussion on the best practice for dealing with
clothing thermophysical properties and underline the need to harmonize the entire
set of standards in the field of the Ergonomics of the Thermal Environment. ISO
7933 is presently under revision.
PMID- 26420267
TI - Incidence of and risk factors for metachronous gastric cancer after endoscopic
resection and successful Helicobacter pylori eradication: results of a large
scale, multicenter cohort study in Japan.
AB - BACKGROUND: A previous multicenter prospective randomized study from Japan showed
that Helicobacter pylori eradication reduced the development of metachronous
gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC
risk, however, is not eliminated; yet few studies have evaluated its long-term
incidence and risk factors. In this study, we investigated the incidence of and
risk factors for MGC in patients who underwent endoscopic resection for early
gastric cancer with successful H. pylori eradication. METHODS: A total of 594
patients who underwent endoscopic resection for early gastric cancer and
successful H. pylori eradication at three institutions (National Cancer Center
Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital)
were analyzed retrospectively. Annual endoscopic surveillance was performed after
initial endoscopic resection. MGC was defined as a gastric cancer newly detected
at least 1 year after successful H. pylori eradication. RESULTS: Ninety-four MGCs
were detected in 79 patients during the 4.5-year median follow-up period. Kaplan
Meier analysis showed the cumulative incidence of MGC 5 years after successful H.
pylori eradication was 15.0 %; the incidence of MGC calculated by use of the
person-year method was 29.9 cases per 1000 person-years. Multivariate analysis
using the Cox proportional hazards model revealed that male sex, severe gastric
mucosal atrophy, and multiple gastric cancers before successful H. pylori
eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of
94) were detected more than 5 years after successful H. pylori eradication.
CONCLUSION: Surveillance endoscopy for MGC in patients who have undergone
endoscopic resection for early gastric cancer should be performed even after
successful H. pylori eradication.
PMID- 26420268
TI - Primary malignant mucosal melanoma of the upper lip: a case report and review of
the literature.
AB - BACKGROUND: Malignant melanoma of oral cavity is a rare condition, accounting for
0.5% of all oral malignancies and about 1-2% of all melanomas. Oral melanomas
have extremely poor prognosis with 5 years survival rate of 12.3%. The poor
prognosis compared to cutaneous melanoma may be attributed to delay in reporting
by patient and diagnosis, and apt to become ulcerated due to repeated trauma. The
'chameleonic' presentation of a mainly asymptomatic condition, the rarity of
these lesions, the poor prognosis and the necessity of a highly specialized
treatment are factors that should be seriously considered by the involved health
provider. CASE PRESENTATION: We present a case of 32 years old male of Han
ethnicity with mucosal melanoma of upper lip, comparing his clinical presentation
and histological findings at his first visit and following the recurrence. The
patient complained of black discoloration on the left side of upper lip since 4
years which gradually increased in size and later involved the skin of the lip.
Excision with 5 mm safety margin was performed but the patient presented with the
similar lesion after three and half years of the treatment. So, again wide
excision with 2 cm safety margin was performed followed by reconstruction of the
lip. CONCLUSION: This case provides an example of aggressive behavior of mucosal
melanoma and emphasizes on the fact that any pigmented lesion detected in the
oral cavity may exhibit potential growth and should be submitted to biopsy to
exclude malignancy. It also exemplifies of how the time of diagnosis and the
evolution of a disease could be seriously influenced by patient's behavior.
PMID- 26420270
TI - Toward an optimized treatment of intracellular bacterial infections: input of
nanoparticulate drug delivery systems.
AB - Intracellular pathogenic bacteria can lead to some of the most life-threatening
infections. By evolving a number of ingenious mechanisms, these bacteria have the
ability to invade, colonize and survive in the host cells in active or latent
forms over prolonged period of time. A variety of nanoparticulate systems have
been developed to optimize the delivery of antibiotics. Main advantages of
nanoparticulate systems as compared with free drugs are an efficient drug
encapsulation, protection from inactivation, targeting infection sites and the
possibility to deliver drugs by overcoming cellular barriers. Nevertheless,
despite the great progresses in treating intracellular infections using
nanoparticulate carriers, some challenges still remain, such as targeting
cellular subcompartments with bacteria and delivering synergistic drug
combinations. Engineered nanoparticles should allow controlling drug release both
inside cells and within the extracellular space before reaching the target cells.
PMID- 26420276
TI - Response to "Letter to Congenital microtia in a neonate suspected of isotretinoin
exposure one month before pregnancy: A case report".
PMID- 26420269
TI - Neurostimulation for cognitive rehabilitation in stroke (NeuroCog): study
protocol for a randomized controlled trial.
AB - BACKGROUND: Stroke patients may present severe cognitive impairments, primarily
related to executive functions. Transcranial direct current stimulation has shown
promising results, with neuromodulatory and neuroplastic effects. This study is a
double-blind, sham-controlled clinical trial aiming to compare the long-term
effects of stimulation in two different cognitive regions after a stroke.
METHODS/DESIGN: Sixty patients who suffer from chronic strokes will be randomized
into one of four groups: dorsolateral prefrontal cortex, cingulo-opercular
network, motor primary cortex and sham stimulation. Each group will receive
transcranial direct current stimulation at an intensity of 2 mA for 20 minutes
daily for 10 consecutive days. Patients will be assessed with a Dysexecutive
Questionnaire, Semantic Fluency Test, categorical verbal fluency and Go-no go
tests, Wechsler Adult Intelligence Scale, Rey Auditory-Verbal Learning Test,
Letter Comparison and Pattern Comparison Tasks at baseline and after their tenth
stimulation session. Those who achieve clinical improvement with neurostimulation
will be invited to receive treatment for 12 months as part of a follow-up study.
DISCUSSION: Long-term stimulation could be analyzed in regard to possible
adaptive changes on plasticity after structural brain damage and if these changes
are different in terms of clinical improvement when applied to two important
cognitive centers. TRIALS REGISTRATION: Clinicaltrials.gov, NCT02315807 . 9
December 2014.
PMID- 26420277
TI - Exploring brain functional plasticity in world class gymnasts: a network
analysis.
AB - Long-term motor skill learning can induce plastic structural and functional
reorganization of the brain. Our previous studies detected brain structural
plasticity related to long-term intensive gymnastic training in world class
gymnasts (WCGs). The goal of this study was to investigate brain functional
plasticity in WCGs by using network measures of brain functional networks.
Specifically, we acquired resting-state fMRI data from 13 WCGs and 14 controls,
constructed their brain functional networks, and compared the differences in
their network parameters. At the whole brain level, we detected significantly
decreased overall functional connectivity (FC) and decreased local and global
efficiency in the WCGs compared to the controls. At the modular level, we found
intra- and inter-modular reorganization in three modules, the cerebellum, the
cingulo-opercular and fronto-parietal networks, in the WCGs. On the nodal level,
we revealed significantly decreased nodal strength and efficiency in several non
rich club regions of these three modules in the WCGs. These results suggested
that functional plasticity can be detected in the brain functional networks of
WCGs, especially in the cerebellum, fronto-parietal network, and cingulo
opercular network. In addition, we found that the FC between the fronto-parietal
network and the sensorimotor network was significantly negatively correlated with
the number of years of training in the WCGs. These findings may help us to
understand the outstanding gymnastic performance of the gymnasts and to reveal
the neural mechanisms that distinguish WCGs from controls.
PMID- 26420279
TI - The timing of language learning shapes brain structure associated with
articulation.
AB - We compared the brain structure of highly proficient simultaneous (two languages
from birth) and sequential (second language after age 5) bilinguals, who differed
only in their degree of native-like accent, to determine how the brain develops
when a skill is acquired from birth versus later in life. For the simultaneous
bilinguals, gray matter density was increased in the left putamen, as well as in
the left posterior insula, right dorsolateral prefrontal cortex, and left and
right occipital cortex. For the sequential bilinguals, gray matter density was
increased in the bilateral premotor cortex. Sequential bilinguals with better
accents also showed greater gray matter density in the left putamen, and in
several additional brain regions important for sensorimotor integration and
speech-motor control. Our findings suggest that second language learning results
in enhanced brain structure of specific brain areas, which depends on whether two
languages are learned simultaneously or sequentially, and on the extent to which
native-like proficiency is acquired.
PMID- 26420278
TI - Lesion-induced and activity-dependent structural plasticity of Purkinje cell
dendritic spines in cerebellar vermis and hemisphere.
AB - Neuroplasticity allows the brain to encode experience and learn behaviors, and
also to re-acquire lost functions after damage. The cerebellum is a suitable
structure to address this topic because of its strong involvement in learning
processes and compensation of lesion-induced deficits. This study was aimed to
characterize the effects of a hemicerebellectomy (HCb) combined or not with the
exposition to environmental enrichment (EE) on dendritic spine density and size
in Purkinje cell proximal and distal compartments of cerebellar vermian and
hemispherical regions. Male Wistar rats were housed in enriched or standard
environments from the 21st post-natal day (pnd) onwards. At the 75th pnd, rats
were submitted to HCb or sham lesion. Neurological symptoms and spatial
performance in the Morris water maze were evaluated. At the end of testing,
morphological analyses assessed dendritic spine density, area, length, and head
diameter on vermian and hemispherical Purkinje cells. All hemicerebellectomized
(HCbed) rats showed motor compensation, but standard-reared HCbed animals
exhibited cognitive impairment that was almost completely compensated in enriched
HCbed rats. The standard-reared HCbed rats showed decreased density with
augmented size of Purkinje cell spines in the vermis, and augmented both density
and size in the hemisphere. Enriched HCbed rats almost completely maintained the
spine density and size induced by EE. Both lesion-induced and activity-dependent
cerebellar plastic changes may be interpreted as "beneficial" brain reactions,
aimed to support behavioral performance rescuing.
PMID- 26420280
TI - Elisabeth Holme.
PMID- 26420281
TI - Quo vadis: the re-definition of "inborn metabolic diseases".
PMID- 26420285
TI - Patient educational technologies and their use by patients diagnosed with
localized prostate cancer.
AB - BACKGROUND: Two urology practices in Calgary, Canada use patient educational
technology (PET) as a core component of their clinical practice. The purpose of
this study was to determine how patients interact with PET designed to inform
them about their treatment options for clinically localized prostate cancer.
METHODS: A PET library was developed with 15 unique prostate-related educational
modules relating to diagnosis, treatment options, and potential side effects. The
PET collected data regarding its use, and those data were used to conduct a
retrospective analysis. Descriptive analyses were conducted and comparisons made
between patients' utilization of the PET library during first and subsequent
access; Pearson's Chi-Square was used to test for statistical significance, where
appropriate. RESULTS: Every patient (n = 394) diagnosed with localized prostate
cancer was given access to the PET library using a unique identifier. Of those,
123 logged into the library and viewed at least one module and 94 patients logged
into the library more than once. The average patient initially viewed modules
pertaining to their diagnosis. Viewing behavior significantly changed in
subsequent logins, moving towards modules pertaining to treatment options,
decision making, and post-surgical information. DISCUSSION: As observed through
the longitudinal utilization of the PET library, information technology offers
clinicians an opportunity to provide an interactive platform to meet patients'
dynamic educational needs. Understanding these needs will help inform the
development of more useful PETs. CONCLUSION: The informational needs of patients
diagnosed with clinically localized prostate cancer changed throughout the course
of their diagnosis and treatment.
PMID- 26420286
TI - NPHS2 mutations account for only 15% of nephrotic syndrome cases.
AB - BACKGROUND: Nephrotic syndrome is traditionally classified on the basis of the
response to standard steroid treatment. Mutations in more than 24 genes have been
associated with nephrotic syndrome in children, although the great majority of
steroid-resistant cases have been attributed to mutations in three main genes:
NPHS1, NPHS2 and WT1. The aims of this study were to identify mutations in these
genes more frequently reported as mutated and to characterize each variation
using different in silico prediction algorithms in order to understand their
biological functions. METHODS: We performed direct sequence analysis of exons 8
and 9 of WT1, 8 exons of NPHS2 and 29 exons of NPHS1, including NPHS2 and NPHS1
intron-exon boundary sequences, as well as 700 bp of the 5' UTR from both genes
in 27 steroid-resistant patients aged between 3 months and 18 years. RESULTS:
Analysis of the NPHS2 gene revealed four missense mutations, one frameshift
mutation and three variations in the 5' UTR. Four patients presented compound
heterozygosis, and four other patients presented one heterozygous alteration
only. WT1 and NPHS1 gene analysis did not reveal any mutations. DISCUSSION: This
is the first study focusing on genetics of SRNS in Brazilian children.
Identification of mutations is important because it could influence physicians'
decision on patient treatment, as patients carrying mutations can be spared the
side effects of immunosuppressive therapy and ultimately could be considered for
kidney transplantation from a living donor. CONCLUSIONS: After molecular analysis
of the genes more frequently reported as mutated in 27 steroid-resistant
nephrotic syndrome patients, we identified NPHS2 mutations confirming the
hereditary character of the kidney disease in only 14.8% of patients. Therefore,
the next step is to perform a next generation sequencing based analysis of
glomeluropathy-related panel of genes for the remaining patients in order to
search for mutations in other genes related to steroid-resistant nephrotic
syndrome.
PMID- 26420288
TI - Significant LVOT obstruction after mitral valve in ring procedure.
PMID- 26420287
TI - FDG-PET reveals improved cardiac regeneration and attenuated adverse remodelling
following Sitagliptin + G-CSF therapy after acute myocardial infarction.
AB - AIMS: Dual therapy comprising G-CSF for mobilization of bone marrow-derived
progenitor cells (BMPCs), with simultaneous pharmacological inhibition of
dipeptidylpeptidase-IV for enhanced myocardial recruitment of circulating BMPC
via the SDF-1alpha/CXCR4-axis, has been shown to improve survival after acute
myocardial infarction (AMI). Using an innovative method to provide non-invasive
serial in vivo measurements and information on metabolic processes, we aimed to
substantiate the possible effects of this therapeutic concept on cardiac
remodelling after AMI using 2-deoxy-2-[18F]fluoro-d-glucose positron emission
tomography (FDG-PET). METHODS AND RESULTS: AMI was induced in C57BL/6 mice by
performing surgical ligation of the left anterior descending artery in these
mice. Animals were then treated with granulocyte-colony stimulating factor +
Sitagliptin (GS) or placebo for a duration of 5 days following AMI. From serial
PET scans, we verified that the infarct size in GS-treated mice (n = 13) was
significantly reduced at Day 30 after AMI when compared with the mice receiving
placebo (n = 10). Analyses showed a normalized FDG uptake on Day 6 in GS-treated
mice, indicating an attenuation of the cardiac inflammatory response to AMI in
treated animals. Furthermore, flow cytometry showed a significant increase in the
anti-inflammatory M2-macrophages subpopulation in GS-treated animals. In
comparing GS treated with placebo animals, those receiving GS-therapy showed a
reduction in myocardial hypertrophy and left ventricular dilatation, which
indicates the beneficial effect of GS treatment on cardiac remodelling.
Remarkably, flow cytometry and immunohistochemistry showed an increase of
myocardial c-kit positive cells in treated mice (n = 12 in both groups).
CONCLUSION: Using the innovative method of micro-PET for non-invasive serial in
vivo measurements of metabolic myocardial processes in mice, we were able to
provide mechanistic evidence that GS therapy improves cardiac regeneration and
reduces adverse remodelling after AMI.
PMID- 26420289
TI - Perforated aortic valve aneurysm in infective endocarditis: from vegetation to
aneurysm.
PMID- 26420290
TI - Anomalous bilateral pulmonary veins with normal drainage into the left atrium.
PMID- 26420291
TI - Incremental predictive value for obstructive coronary artery disease by
combination of Duke Clinical Score and Agatston score.
AB - AIMS: Recent study suggests that algorithms such as the Duke Clinical score (DCS)
may overestimate the pretest probability. The Agatston score representing the
grade of coronary artery calcification can be simply calculated from low
radiation exposure ECG-gated plain CT. In this study, we investigated whether or
not more superior diagnostic performance for obstructive coronary artery disease
(CAD) can be obtained by combining DCS with the Agatston score. METHODS AND
RESULTS: Of 3939 consecutive patients suspected of having stable angina without
known CAD who underwent Coronary Computed Tomography Angiography (CCTA) as well
as calculation of the DCS and Agatston score at our hospital, 3688 patients were
selected as subjects. Obstructive CAD was defined as >50% diameter stenosis on
CCTA; we investigated the diagnostic performance based on the area under the
curve (AUC) of a receiver operating characteristic (ROC) curve, Net
Reclassification Improvement (NRI), and Integrated Discrimination Improvement
(IDI). The AUCs of ROCs prepared using the DCS alone and combination of the DCS
and Agatston score were 0.7137 and 0.8057, respectively, showing that the
diagnostic performance of the combination was significantly superior to DCS alone
(P < 0.001). NRI was 0.8132 and IDI was 0.1374, showing that the diagnostic
performance was improved by the combination of the DCS and Agatston score
compared with DCS alone (P < 0.001). NRI (0.3522) and IDI (0.0287) were improved
compared with those of the Agatston score alone (P < 0.001). CONCLUSION: The
combination of the DCS and Agatston score improved the diagnostic performance for
obstructive CAD compared with DCS alone and Agatston score.
PMID- 26420292
TI - FDG-PET/CT for driveline infection in a patient with implantable left ventricular
assist device.
PMID- 26420293
TI - Double-orifice mitral valve in Ebstein's anomaly.
PMID- 26420295
TI - Epigenetic analysis of regulatory T cells using multiplex bisulfite sequencing.
PMID- 26420294
TI - Sirtuins in Cancer: a Balancing Act between Genome Stability and Metabolism.
AB - Genomic instability and altered metabolism are key features of most cancers.
Recent studies suggest that metabolic reprogramming is part of a systematic
response to cellular DNA damage. Thus, defining the molecules that fine-tune
metabolism in response to DNA damage will enhance our understanding of molecular
mechanisms of tumorigenesis and have profound implications for the development of
strategies for cancer therapy. Sirtuins have been established as critical
regulators in cellular homeostasis and physiology. Here, we review the emerging
data revealing a pivotal function of sirtuins in genome maintenance and cell
metabolism, and highlight current advances about the phenotypic consequences of
defects in these critical regulators in tumorigenesis. While many questions
should be addressed about the regulation and context-dependent functions of
sirtuins, it appears clear that sirtuins may provide a promising, exciting new
avenue for cancer therapy.
PMID- 26420296
TI - Expression Profile Analysis of miR-221 and miR-222 in Different Tissues and Head
Kidney Cells of Cynoglossus semilaevis, Following Pathogen Infection.
AB - Half-smooth tongue sole (Cynoglossus semilaevis) is an important marine
commercial fish species in China, which suffers from widespread disease
outbreaks. Recently, in this regard, our group identified immune-related
microRNAs (miRNAs) of C. semilaevis following Vibrio anguillarum infection.
Furthermore, miRNA microarray was utilized to characterize the immune roles of
important miRNA candidates in response to bacterial infection. Therefore, in the
present study, we characterized miR-221 and miR-222 and profiled their expression
after challenge. Here, miR-221 and miR-222 precursors were predicted to have a
typical hairpin structure. Both miRNAs were expressed in a broad range of tissues
in C. semilaevis, while miR-221 and miR-222 were significantly differentially
expressed in the immune tissues of C. semilaevis among three small RNA libraries
[control group (CG), bacteria-challenged fish without obvious symptoms of
infection (NOSG), and bacteria-challenged fish with obvious symptoms of infection
(HOSG)]. In order to further characterize and understand the immune response of
miR-221 and miR-222, therefore, we profiled miR-221 and miR-222 expression in
selected immune tissues after challenge with V. anguillarum. Both miR-221 and miR
222 were upregulated in the liver and spleen, while different expression patterns
were observed in the head kidney. In addition, in half-smooth tongue sole head
kidney cell line after challenge with lipopolysaccharide (LPS),
polyinosinic:polycytidylic acid (poly I:C), peptidoglycan (PGN), and red-spotted
grouper nervous necrosis virus (RGNNV), both miR-221 and miR-222 showed
significant difference in expression response to pathogen. Meanwhile, the target
gene of miR-221 and miR-222 was predicted, which indicated that tumor necrosis
factor receptor-associated factor 6 (TRAF6) and interleukin-1 beta (IL-1beta)
were the target genes of miR-221 and miR-222, respectively. Collectively, these
findings indicated that miR-221 and miR-222 have putative roles in innate immune
response during C. semilaevis exposure to pathogens. Our findings could expand
the knowledge of immune function of C. semilaevis miRNA and guide future studies
on C. semilaevis immunity.
PMID- 26420297
TI - Multimodality Imaging of Cancer Superoxide Anion Using the Small Molecule
Coelenterazine.
AB - PURPOSE: We evaluated the small molecule coelenterazine as a potential reporter
of cancer-associated superoxide anion in cell culture and in mice. PROCEDURES:
The superoxide anion concentrations of various cancer cell lines were quantified
by coelenterazine chemiluminescence in vitro. Coelenteramide fluorescence was
detected via flow cytometry and fluorescent microscopy. Coelenterazine was used
for the in vivo detection of cancer-associated superoxide anion using the 4T1
breast adenocarcinoma mouse model. RESULTS: Various cell lines in culture
demonstrated different superoxide anion concentrations, with a signal range of
3.15 +/- 0.06 to 11.80 +/- 0.24 times that of background. In addition to
chemiluminescent detection of coelenterazine, we demonstrated fluorescent
detection of coelenteramide within the cytoplasm of cells. 4T1 murine mammary
adenocarcinoma tumors in mice demonstrated significantly higher 2.13 +/- 0.19
fold coelenterazine-based chemiluminescence than that of surrounding normal
tissues. CONCLUSIONS: Collectively, our results indicate that coelenterazine can
be used to assay superoxide anion concentrations in cultured cancer cells and in
tumors growing in mice.
PMID- 26420298
TI - Impaired processing of self-face recognition in anorexia nervosa.
AB - Body image disturbances and massive weight loss are major clinical symptoms of
anorexia nervosa (AN). The aim of the present study was to examine the influence
of body changes and eating attitudes on self-face recognition ability in AN.
Twenty-seven subjects suffering from AN and 27 control participants performed a
self-face recognition task (SFRT). During the task, digital morphs between their
own face and a gender-matched unfamiliar face were presented in a random
sequence. Participants' self-face recognition failures, cognitive flexibility,
body concern and eating habits were assessed with the Self-Face Recognition
Questionnaire (SFRQ), Trail Making Test (TMT), Body Shape Questionnaire (BSQ) and
Eating Disorder Inventory-2 (EDI-2), respectively. Subjects suffering from AN
exhibited significantly greater difficulties than control participants in
identifying their own face (p = 0.028). No significant difference was observed
between the two groups for TMT (all p > 0.1, non-significant). Regarding
predictors of self-face recognition skills, there was a negative correlation
between SFRT and body mass index (p = 0.01) and a positive correlation between
SFRQ and EDI-2 (p < 0.001) or BSQ (p < 0.001). Among factors involved,
nutritional status and intensity of eating disorders could play a part in
impaired self-face recognition.
PMID- 26420299
TI - Perceived vulnerability to disease and antifat attitudes in a sample of children
and teenagers.
AB - PURPOSE: Perceived vulnerability to disease (beliefs about personal
susceptibility to contracting an infectious disease) is usually related to the
expression of prejudice towards different stigmatized groups. In this study, the
relationship between this variable and the expression of the prejudice towards
obese people was analyzed. METHOD: The sample comprised a total of 137 children
and teenagers, aged between 12 and 17 years, from a Spanish high school who
fulfilled several scales which measure perceived vulnerability to disease,
antifat attitudes and perceived controllability of weight. Additionally, body
mass index (BMI) was calculated by means of the participants' height and weight.
RESULTS: Perceived infectability (one of the factors of the perceived
vulnerability to disease scale) was negatively related to controllability of
weight, and germ aversion (the second factor of the vulnerability scale), showed
a positive relationship with the antipathy towards obese people. Finally,
perceived controllability of weight was positively correlated with BMI.
CONCLUSIONS: The implications of these results in the field of the study of the
prejudice toward obese people are discussed. To our knowledge, no other studies
have investigated the relationship between perceived vulnerability to disease and
antifat attitudes in minors. Additionally, this is the first time that the
measured BMI has been used instead of the self-reported one.
PMID- 26420300
TI - Myhre syndrome: Clinical features and restrictive cardiopulmonary complications.
AB - Myhre syndrome, a connective tissue disorder characterized by deafness,
restricted joint movement, compact body habitus, and distinctive craniofacial and
skeletal features, is caused by heterozygous mutations in SMAD4. Cardiac
manifestations reported to date have included patent ductus arteriosus, septal
defects, aortic coarctation and pericarditis. We present five previously
unreported patients with Myhre syndrome. Despite varied clinical phenotypes all
had significant cardiac and/or pulmonary pathology and abnormal wound healing.
Included herein is the first report of cardiac transplantation in patients with
Myhre syndrome. A progressive and markedly abnormal fibroproliferative response
to surgical intervention is a newly delineated complication that occurred in all
patients and contributes to our understanding of the natural history of this
disorder. We recommend routine cardiopulmonary surveillance for patients with
Myhre syndrome. Surgical intervention should be approached with extreme caution
and with as little invasion as possible as the propensity to develop
fibrosis/scar tissue is dramatic and can cause significant morbidity and
mortality.
PMID- 26420301
TI - Hepatitis B surface gene variants isolated from blood donors with overt and
occult HBV infection in north eastern Egypt.
AB - BACKGROUND: Major hydrophilic region in genomic HBV extending from aa99 to aa169,
clustered with a highly conformational epitope, is critical to the antigenicity
of hepatitis B surface antigen (HBsAg) and may affect the diagnosis of HBV in HBV
screening test. So, this study aimed to characterize variants of S gene product
of hepatitis B virus (HBV) isolated from patients with overt or occult HBV
infection in north-eastern Egypt. METHODS: The study included sera of two
different groups of volunteer blood donors (VBDs), 82 with overt HBV that were
positive for HBsAg and anti-HBc and 343 donors negative for HBsAg eligible for
donation. Of the latter group, only 44 were positive for anti-HBc. All anti-HBc
positive sera were subjected to HBV DNA detection and partial sequence analysis
targeting the HBV S gene. RESULTS: HBV DNA was detected in 22.7 % of HBsAg-/anti
HBc + (10/44 patients) and in 90 % of HBsAg + donors (74/82 patients) with
significant statistical difference (P = 0.0001). Phylogenetic analysis showed
that HBV strains retrieved from both groups were of genotype D. Amino acid escape
mutation T125M was detected in only 2 samples of the occult infection group and
in none of the overt group (P = 0.01). Different amino acid substitutions were
identified in overt infection group: S143L/T (16.2 %, 12/74) and P120T/S (2.7 %,
2/74). Q129R was significantly more frequent in cases with occult HBV infection
(40 %, 4/10) than overt group (6.8 %, 5/74) (P = 0.01). CONCLUSIONS: HBV genotype
D predominated both in patients with overt and occult HBV infection. Different
profiles of amino acid substitutions in the major hydrophilic region were seen in
these two groups in Egypt.
PMID- 26420302
TI - Antibiotic use and resistance: a cross-sectional study exploring knowledge and
attitudes among school and institution personnel in Tbilisi, Republic of Georgia.
AB - BACKGROUND: The Republic of Georgia lacks regulations regarding drug
prescriptions. In pharmacies, all drugs except psychotropic medication are sold
legally without prescription anti-, including anti-tuberculosis agents. Due to
the lack of adequate policies and regulations, the big share of responsibility
regarding antibiotic education lies with the general public. This study examines
public knowledge and attitudes toward antibiotic use and resistance in the
Republic of Georgia among personnel from government schools and other public
institutions. METHODS: This cross-sectional study was conducted in June 2011
using a quantitative questionnaire. Convenience sampling method was used.
Participants included 250 individuals aged 21-80 years, from government schools
and public institutions. Participants were from Tbilisi as well as the
surrounding rural and urban areas. Respondents provided demographic data along
with statements on knowledge and attitudes towards antibiotic use and resistance.
Poisson and logistic regression models were used to study the relationship
between knowledge, attitude outcomes and socio-demographic characteristics.
RESULTS: The overall response rate was 75% (n = 187), of which 80% were female.
Approximately 91% of respondents had used antibiotics at least once and 55%
agreed that antibiotics speed up recovery from common colds. A number of
respondents (55%) reported having received antibiotics without previously
consulting a doctor and 62% reported having purchased antibiotics without a
prescription. Respondents demonstrated some misunderstanding around the terms
'bacteria' and 'virus.' About 52% of participants agreed that antibiotics are
effective against bacteria; however, 55% also agreed that antibiotics are
effective against viruses. Trust in doctors was high at 80%. More knowledge was
associated with a lower probability of having purchased antibiotics without
medical consultation. CONCLUSIONS: The study findings demonstrate that
respondents have several misconceptions and lack knowledge on proper antibiotic
use and resistance. High proportion of people use antibiotics without a medical
prescription or consultation, while having high trust in the medical personnel.
We believe that the high level of trust in doctors shown by our respondents
should be acknowledged by the Georgian government, health care providers and
public health policy professionals. Furthermore, the information should be
utilized in future educational and antibiotic resistance awareness raising
campaigns.
PMID- 26420303
TI - Efficacy of a pressure-sensing mattress cover system for reducing interface
pressure: study protocol for a randomized controlled trial.
AB - BACKGROUND: Interface pressure is a key risk factor in the development of
pressure ulcers. Visual feedback of continuous interface pressure between the
body and support surface could inform clinicians on repositioning strategies and
play a key role in an overall strategy for the prevention and management of
pressure ulcers. METHODS/DESIGN: A parallel two-group randomized controlled
clinical trial will be conducted to study the effect of continuous pressure
imaging on reducing interface pressure and on the incidence of pressure ulcers in
vulnerable hospital patients. A total of 678 eligible consenting inpatients at
risk of pressure ulcer development in a tertiary acute care institution will be
randomly allocated to either having the ForeSite PTTM system with the liquid
crystal display monitor turned on to provide visual feedback to the clinicians
while also collecting continuous interface pressure data (intervention group) or
to having the ForeSite PTTM system with monitor turned off (that is, not
providing visual feedback) but still collecting continuous interface pressure
data (control group), in a ratio of 1:1. Continuous interface pressure data will
be collected in both groups for 3 days (72 h). Data collection will continue
until discharge for a subset of approximately 60 patients. The primary outcome
will be the differences in the two groups' interface pressure analysis. Interface
pressure readings will be collected through hourly samplings of continuous
interface pressure recordings. Secondary outcomes will be the differences between
the two groups in pressure-related skin and soft tissue changes in areas at risk
of pressure ulcer (obtained at baseline within 24 h of admission) and on the
third day of the trial or at discharge and perceptions of the intervention by
patients and clinicians (obtained on the third day or at discharge). DISCUSSION:
This will be the first randomized controlled trial to investigate the effect of
visual feedback with continuous interface pressure of vulnerable hospital
patients across different care settings, and the association between interface
pressure and development of pressure-related skin and soft tissue changes. The
results could provide important information to guide clinical practice in the
prevention and management of pressure ulcers. TRIALS REGISTRATION:
ClinicalTrials.gov NCT02325388 (date of registration: 24 December 2014).
PMID- 26420305
TI - Synthesis and self-assembly of carbamoylmethylphosphonate acrylamide-based
diblock copolymers: new valuable thermosensitive materials.
AB - We report the synthesis by RAFT polymerization of well-defined diblock copolymers
bearing carbamoylmethylphosphonate moieties which proved to sorb gadolinium.
These poly(diethyl-6-(acrylamido)hexylcarbamoylmethylphosphonate-b-acrylic acid)
(P(CPAAm6C-b-AA)) copolymers were able to self-assemble as a function of
temperature, above their cloud point value.
PMID- 26420304
TI - Metabolomics in childhood diabetes.
AB - Recent increases in the incidence of both type 1 (T1D) and type 2 diabetes (T2D)
in children and adolescents point to the importance of environmental factors in
the development of these diseases. Metabolomic analysis explores the integrated
response of the organism to environmental changes. Metabolic profiling can
identify biomarkers that are predictive of disease incidence and development,
potentially providing insight into disease pathogenesis. This review provides an
overview of the role of metabolomic analysis in diabetes research and summarizes
recent research relating to the development of T1D and T2D in children.
PMID- 26420306
TI - Antibacterial Mechanism of (-)-Nortrachelogenin in Escherichia coli O157.
AB - (-)-Nortrachelogenin is a lignan belonging to group of polyphenolic compounds.
Its biological properties in mammalian cells are well-studied; however, its
biological effects in microorganisms remain poorly understood. Its efficacy
against pathogenic bacteria, including antibiotic-resistant strains, was
investigated and it was found that bacteria are highly susceptible to the
antibacterial effects of this compound. To investigate the antibacterial mode of
action(s) against Escherichia coli O157, its effect on the penetration of SYTOX
green into bacterial cells was assayed. The penetration of SYTOX Green into a
bacterial cell is a measure of permeability of the plasma membrane. An increase
in fluorescence intensity using bis-(1,3-dibutylbarbituric acid) trimethine
oxonol [DiBAC4(3)] and 3,3'-dipropylthiacarbocyanine iodide [DiSC3(5)] was also
observed, indicating membrane depolarization. Potassium ion efflux from the
cytosol into the extracellular matrix showed that cellular damage due to (-)
nortrachelogenin treatment resulted in the loss of intracellular components.
While cells were damaged by (-)-nortrachelogenin, large unilamellar vesicles
containing fluorescein isothiocyanate-dextran were perturbed to migrate molecules
between 3.3 and 4.8 nm. The release of calcein from giant unilamellar vesicles,
occurring as a result of disruption in artificial membranes, was visualized.
Taken together, our results indicate that (-)-nortrachelogenin exerts its
antibacterial effect by disorganizing and perturbing the cytoplasmic membrane,
demonstrating the potential of this compound as a candidate for antibiotic drug
development.
PMID- 26420309
TI - Pharmacist independent prescribing in critical care: results of a national
questionnaire to establish the 2014 UK position.
AB - OBJECTIVES: Clinical pharmacist practice is well established in the safe and
effective use of medicines in the critically ill patient. In the UK, independent
pharmacist prescribers are generally recognised as a valuable and desirable
resource. However, currently, there are only anecdotal reports of pharmacist
independent prescribing in critical care. The aim of this questionnaire was to
determine the current and proposed future independent prescribing practice of UK
clinical pharmacists working in adult critical care. METHODS: The questionnaire
was distributed electronically to UK Clinical Pharmacy Association members
(closed August 2014). KEY FINDINGS: There were 134 responses to the questionnaire
(response rate at least 33%). Over a third of critical care pharmacists were
practising independent prescribers in the specialty, and 70% intended to be
prescribers within the next 3 years. Pharmacists with >=5 years critical care
experience (P < 0.001) or worked in a team (P = 0.005) were more likely to be
practising independent prescribers. Pharmacists reported significant positives to
the use of independent prescribing in critical care both in patient care and job
satisfaction. Independently, prescribing was routine in: dose adjustment for
multi-organ failure, change in route or formulation, correction prescribing
errors, therapeutic drug monitoring and chronic medication. The majority of
pharmacist prescribers reported they spent <=5% of their clinical time
prescribing and accounted for <=5% of new prescriptions in critical care
patients. CONCLUSIONS: Most critical care pharmacists intend to be practising as
independent prescribers within the next 3 years. The extent and scope of critical
care pharmacist prescribing appear to be of relatively low volume and within
niche prescribing areas.
PMID- 26420310
TI - Hexaphenylbenzene-Stabilized Luminescent Silver Nanoclusters: A Potential
Catalytic System for the Cycloaddition of Terminal Alkynes with Isocyanides.
AB - A hexaphenylbenzene (HPB)-based derivative bearing thiol groups has been designed
and synthesized that undergoes aggregation-induced emission enhancement in mixed
aqueous media to form rodlike fluorescent aggregates. These rodlike aggregates
behave as a "not quenched" probe for the detection of silver ions and further act
as reactors and stabilizers for reducing-agent-free preparation of blue
luminescent silver nanoclusters at room temperature. The utilization of
fluorescent supramolecular aggregates for the preparation of Ag NCs in mixed
aqueous media is unprecedented in the literature. Moreover, the wet chemical
method that we are reporting in the present paper for the preparation of
luminescent silver nanoclusters is better than the other methods reported in the
literature. Further, these in situ generated Ag NCs showed exceptional catalytic
activity in the preparation of pyrroles involving cocyclization of isocyanides
and terminal alkynes. Interestingly, the catalytic efficiency of in situ
generated Ag NCs was found to be better than the other catalytic systems reported
in the literature.
PMID- 26420308
TI - Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT,
enlarge the parasite's food vacuole and alter drug sensitivities.
AB - Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT,
are the major determinant of chloroquine resistance in this lethal human malaria
parasite. Here, we describe P. falciparum lines subjected to selection by
amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing
the development of enlarged food vacuoles. These parasites also have increased
sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no
or minimal change in sensitivity to artemisinins, when compared with parental
strains. A transgenic parasite line expressing the L272F variant of PfCRT
confirmed this increased chloroquine sensitivity and enlarged food vacuole
phenotype. Furthermore, the introduction of the C101F or L272F mutation into a
chloroquine-resistant variant of PfCRT reduced the ability of this protein to
transport chloroquine by approximately 93 and 82%, respectively, when expressed
in Xenopus oocytes. These data provide, at least in part, a mechanistic
explanation for the increased sensitivity of the mutant parasite lines to
chloroquine. Taken together, these findings provide new insights into PfCRT
function and PfCRT-mediated drug resistance, as well as the food vacuole, which
is an important target of many antimalarial drugs.
PMID- 26420311
TI - Proximal humerus allograft prosthetic composites: technique, outcomes, and pearls
and pitfalls.
AB - The proximal humerus is the second most common location of primary bone sarcomas
and a frequent location of benign locally aggressive primary osseous tumors. In
contrast to other locations, tumors in this region impose significant challenges
for local control and reconstruction. This is due to glenohumeral joint anatomic
characteristics such as lack of intrinsic stability and dependence on dynamic and
static stabilizers. In addition, the close proximity of the axillary nerve and
axillary vascular bundle places these at risk of resection when attaining local
control. Allograft prosthetic composites (APCs) of the proximal humerus are one
of the methods for mobile reconstruction. This modality presents lower fracture
rates when compared to osteoarticular allografts and lower rates of subluxation
and instability than endoprosthesis. Recent literature documents a trend for
superior functional outcome at comparable complication rates. APC reconstruction
is an important tool in the orthopedic oncologist armamentarium.
PMID- 26420313
TI - [Anniversary symposium of the Israeli-German Dermatological Society].
PMID- 26420312
TI - Autoinducer-2 regulates Pseudomonas aeruginosa PAO1 biofilm formation and
virulence production in a dose-dependent manner.
AB - BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that is the
leading cause of iatrogenic infections in critically ill patients, especially
those undergoing mechanical ventilation. In this study, we investigated the
effects of the universal signaling molecule autoinducer-2 (AI-2) in biofilm
formation of P. aeruginosa PAO1. RESULTS: The addition of 0.1 nM, 1 nM, and 10 nM
exogenous AI-2 to P. aeruginosa PAO1 increased biofilm formation, bacterial
viability, and the production of virulence factors. However, compared to the 10
nM AI-2 group, higher concentrations of AI-2 (100 nM and 1 MUM) reduced biofilm
formation, bacterial viability, and the production of virulence factors.
Consistent with the changes in morphology, gene expression analysis revealed that
AI-2 up-regulated the expression of quorum sensing-associated genes and genes
encoding virulence factors at lower concentrations and down-regulated these genes
at higher concentrations. CONCLUSIONS: Our study demonstrated that exogenous AI-2
acted in a dose-dependent manner to regulate P. aeruginosa biofilm formation and
virulence factors secretion via modulating the expression of quorum sensing
associated genes and may be targeted to treat P. aeruginosa biofilm infections.
PMID- 26420315
TI - [Greater emphasis should be placed on exercise program of rehabilitation for
patients with coronary artery disease].
PMID- 26420316
TI - [Interpretation and assessment of Joint British Societies' consensus
recommendations for the prevention of cardiovascular disease (JBS3)].
PMID- 26420314
TI - An empirical comparison of the OPQoL-Brief, EQ-5D-3 L and ASCOT in a community
dwelling population of older people.
AB - BACKGROUND: This study examined the relationships between a newly developed older
person-specific non-preference-based quality of life (QoL) instrument (Older
People's Quality of Life brief questionnaire (OPQoL-brief)) and two generic
preference-based instruments (the EQ-5D-3L Level (EQ-5D-3 L) and the Adult Social
Care Outcomes Toolkit (ASCOT) in a community-dwelling population of Australian
older people receiving aged care services. METHODS: We formulated hypotheses
about the convergent validity between the instruments (examined by Wilcoxon-Mann
Whitney, Kruskal Wallis and Spearman's correlation tests) and levels of agreement
(assessed using intra class correlation (ICC) and modified Bland-Altman plots
based on normalized Z EQ-5D-3 L and ASCOT utilities and OPQoL-Brief summary
scores). RESULTS: The utilities/summary scores for 87 participants (aged 65-93
years) were moderately but positively correlated. Moderate convergent validity
was evident for a number of instrument dimensions with the strongest relationship
(r = 0.57) between 'enjoy life' (OPQoL-Brief) and 'social contact' (ASCOT). The
overall ICC was 0.54 and Bland-Altman scatter plots showed 3-6% of normalized Z
scores were outside the 95% limits of agreement suggesting moderate agreement
between all three instruments (agreement highest between the OPQoL-Brief and the
ASCOT). CONCLUSIONS: Our results suggest that the OPQoL-Brief, the ASCOT and the
EQ-5D_3L are suitable for measuring quality of life outcomes in community
dwelling populations of older people. Given the different constructs underpinning
these instruments, we recommend that choice of instrument should be guided by the
context in which the instruments are being applied. Currently, the OPQoL-Brief is
not suitable for use in cost-utility analyses as it is not preference-based.
Given their different perspectives, we recommend that both the ASCOT and the EQ
5D are applied simultaneously to capture broader aspects of quality of life and
health status within cost-utility analyses within the aged care sector. Future
research directed towards the development of a new single preference-based
instrument that incorporates both health status and broader aspects of quality of
life within quality adjusted life year calculations for older people would be
beneficial.
PMID- 26420317
TI - [Chinese expert consensus on exercise-based rehabilitation for patients with
coronary heart disease].
PMID- 26420318
TI - [Predictors of atrial fibrillation recurrence after catheter ablation in
hypertrophic cardiomyopathy patients with atrial fibrillation].
AB - OBJECTIVE: To evaluate the efficacy of catheter ablation in Chinese hypertrophic
cardiomyopathy (HCM) patients with atrial fibrillation (AF), and to determine the
risk factors of AF recurrence. METHODS: This study enrolled 40 HCM patients with
AF who underwent primary AF ablation at Beijing Anzhen Hospital from June 2005 to
June 2013. Ablation strategy included bilateral pulmonary vein isolation (PVI)
for paroxysmal AF (n = 27) and PVI plus left atrial roof, mitral isthmus and
tricuspid isthmus linear ablations for persistent AF (n = 13). AF recurrence was
followed-up by means of electrocardiography or Holter monitoring. Risk factors
associated with AF recurrence were determined by a Cox regression model and the
predictive power was evaluated by receiver operating characteristic (ROC) curve.
RESULTS: After (34 +/- 18) months follow-up, 30% (12/40) cases remained in sinus
rhythm off antiarrhythmic drug, most AF recurrence (18/28, 64.3%) occurred within
1 year post ablation. Multivariate Cox regression demonstrated that left atrial
dimension (LAD, HR = 1.124, 95% CI 1.051-1.202, P = 0.001) and female gender (HR
= 3.304, 95% CI 1.397-7.817, P = 0.007) were independent risk factors of AF
recurrence. The cut-off value of LAD at 43.5 mm predicted AF recurrence with
sensitivity of 93.5% and specificity of 60.0%. Every 1 mm enlargement in LAD was
associated with an increased risk of arrhythmia recurrence (HR = 1.095, 95% CI
1.031-1.163, P = 0.003). CONCLUSIONS: AF ablation in Chinese HCM patients is safe
and feasible. However, sinus rhythm maintenance rate is low at long-time follow
up. Most of the recurrent AF occurs within 1 year post AF ablation procedure.
Left atrial diameter and female gender are independent risk factors of AF
recurrence.
PMID- 26420319
TI - [Contribution of atrial activation to the segment of the typical atrial flutter
wave: an electro-anatomic insight into the electrocardiogram morphology].
AB - OBJECTIVE: To investigate how the intra-cardiac activation was translates into
the characterized flutter wave in patients with cavatricuspid isthmus-dependent
counter-clockwise atrial flutter (CTI-AFL). METHODS: A total of 15 hospitalized
CTI-AFL patients (mean age: (60 +/- 14) years old, 1 female) from October 2012 to
February 2014 were enrolled in the study. The activation map was re-constructed
during AFL rhythm for left atrium and right atrium using 3-dimensional mapping
system. The flutter wave in surface electrocardiogram was analyzed in combination
with the intra-cardiac activation. RESULTS: The mean left ventricular ejection
fraction was (60.8 +/- 6.6)%, and the left atrial diameter was (39.0 +/- 3.4) mm.
The mean tachycardia cycle length was (220 +/- 24) ms. The activation map was
completed in all cases. In inferior leads, the flutter wave was divided into
three parts: slowly downward part, sharp downward part and the terminal positive
part. The three parts corresponded to the fixed activation part of the macro
reentry. CONCLUSION: The distinctive flutter wave of CTI-AFL was determined by
the unique macro-reentry activation in the right atrium. The activation of left
atrium contributes to the downward part of the wave.
PMID- 26420320
TI - [Left ventricular systolic synchrony assessed by phase analysis of gated
myocardial perfusion imaging in patients with old myocardial infarction].
AB - OBJECTIVE: To assess the left ventricular (LV) systolic synchrony by phase
analysis of gated myocardial perfusion imaging (GMPI) with SPECT/CT in patients
with old myocardial infarction (OMI) and further to identify independent
predictors for LV dyssynchrony. METHODS: Seventy-six OMI patients and seventy
four healthy volunteers (control group) underwent resting GMPI from October 2010
to September 2013 in our hospital were included in this study. The left
ventricular systolic synchrony parameters including phase histogram bandwidth
(BW) and phase standard deviation (SD) were obtained by Cedars-Sinai quantitative
gated SPECT (QGS) phase analysis technique, and LV cardiac function was also
measured. The extent of myocardial perfusion defect was analyzed by the
Quantitative Perfusion SPECT (QPS) software. The value of BW and SD were compared
between OMI and the control groups, between LVEF <= 35% and LVEF > 35% groups in
OMI patients. Dyssynchrony was defined when the BW exceeded the abnormality
threshold derived from a normal control group (threshold = x +/- 2s for normal
BW). RESULTS: (1) The BW ((91.3 +/- 58.6) degrees vs. (37.2 +/- 11.7) degrees )
and SD ((27.3 +/- 20.8) degrees vs. (11.8 +/- 5.4) degrees ) were significantly
higher and the LVEF was significantly lower in OMI group than in the normal
control group (all P < 0.01). In addition, BW ((136.0 +/- 52.9) degrees vs.
(51.0 +/- 24.0) degrees ) and SD ((38.7 +/- 21.3) degrees vs. (17.1 +/- 14.0)
degrees ) were significantly higher in patients with LVEF <= 35% than in patients
with LVEF > 35% (all P < 0.001). (2) Dyssynchrony (BW > 60.6 degrees ) prevalence
was 57.9% (44/76) in OMI patients. Compared with the synchrony group, LVEF was
significantly lower, while the left ventricular end-diastolic volume, end
systolic volume, summed motion score, summed thickening score and extent were
significantly higher in dyssynchrony group (all P < 0.001). (3) Additionally,
dyssynchrony prevalence was significantly higher in patients with LVEF <= 35%
compared with patients with LVEF > 35% (91.7% (33/36) vs. 27.5% (11/40), P <
0.001). (4) Pearson correlation analysis showed that LVEF was negatively
correlated with BW (r = -0.807, P < 0.001). (5) Multivariate logistic regression
analysis revealed that the extent of myocardial perfusion defect was an
independent predictor for dyssynchrony in OMI patients (OR = 1.076, 95% CI: 1.015
1.141, P = 0.015). CONCLUSIONS: GMPI phase analysis can reliably reflect left
ventricular systolic synchrony. The left ventricular systolic dyssynchrony in OMI
patients is significantly increased. Left ventricular dyssynchrony is closely
related to LVEF. The extent of myocardial perfusion defect (Extent) is an
independent predictor for left ventricular systolic dyssynchrony in OMI patients.
PMID- 26420321
TI - [A qualitative research on the psychological experience of hospitalized patients
with acute myocardial infarction].
AB - OBJECTIVE: To observe the psychological experience of patients with acute
myocardial infarction (AMI) during hospitalization. METHODS: From November 2012
to February 2013, semi-structured interviews were conducted in 10 patients with
AMI in the Cardiovascular Department of First Affiliated Hospital of Henan
University of Science and Technology. Grounded theory approach was performed to
analyze the collected data. RESULTS: The 6 themes and 3 secondary themes during
their hospitalization were: helplessness and dependence when AMI was diagnosed
fear of immediate death induced by AMI, confusion on various problems such as
operation time, excretory after PCI and limited knowledge details, the feel of
safety after PCI, the fear of AMI, and the worry about overtreatment.
CONCLUSIONS: Hospitalized AMI patients have complicated psychological responses.
Medical staff should provide targeted strategies and timely communication with
AMI patients to reduce their psychological burden.
PMID- 26420322
TI - [Effect of ethanol and its metabolites on acetylcholine-sensitive K(+) channel
Kir3.1 protein expression of neonatal rat primary atrial cardiomyocytes].
AB - OBJECTIVE: To identify the effect of ethanol and its metabolite acetaldehyde on
acetylcholine-sensitive K(+) channel Kir3.1 protein expression, and explore the
potential role of this channel and acetaldehyde in arrhythmia caused by acute
alcoholic intoxication. METHODS: Primary atrial cardiomyocytes were isolated from
150 newborn SD rats by typsin and type II collagenase, cultured and troponin I
was determined by immunofluorescence. Cell survival in 200-800 mmol/L ethanol or
50-500 umol/L acetaldehyde treated cells for 24 hours was measured by CCK-8 assay
to determine the concentration of ethanol and acetaldehyde for inducing apoptosis
in cardiomyocytes. The highest non-apoptotic concentration (200 mmol/L) of
ethanol and acetaldehyde (100 umol/L) was used in the main study. Kir3.1 protein
expression was detected by Western blot. RESULTS: (1) Cellular immunofluorescence
results showed that cultured cells are cardiomyocytes, and more than 90% of these
cells are troponin I positive. (2) CCK-8 assay demonstrated that the survival
rate of cardiomyocytes in the groups treated by ethanol over 400 mmol/L for 24
hours or acetaldehyde over 400 umol/L was significantly lower than that of the
control group (P < 0.05), while the survival rate was similar in cardiomyocytes
treated by ethanol less than 200 mmol/L or acetaldehyde less than 350 umol/L for
24 hours and the control group (P > 0.05). (3) Western-bolt assay revealed that
ethanol and acetaldehyde treatment for 24 hours upregulated Kir3.1 protein
expression in primary atrial cardiomyocytes of newborn SD rats by (44.52 +/-
23.07)% and (45.04 +/- 22.01)% respectively compared with the control group (all
P < 0.01). CONCLUSIONS: Acute ethanol and acetaldehyde treatment could
significantly upregulate the protein expression of acetylcholine-sensitive K(+)
channel Kir3.1, this might serve as a potential mechanism for arrhythmia caused
by acute alcoholic intoxication.
PMID- 26420323
TI - [Nuclear factor-kappaB pathway mediates the effects of CD137 signaling on NFATc1
expression in mice vascular smooth muscle cells].
AB - OBJECTIVE: To observe whether CD137 signaling could affect the nuclear factor of
activated T cells c1 (NFATc1) expression through nuclear factor-kappaB (NF
kappaB) pathway in mice aortic vascular smooth muscle cells (VSMCs). METHODS:
Adherence methods for tissues explants were used for primary culture of mouse
aortic VSMCs. The mRNA expression of CD137 and NFATc1 was detected by real-time
quantitative PCR (RT-qPCR). The VSMCs protein expression of IkappaB-alpha, NF
kappaB p65, phospo-p65 and NFATc1 was determined by Western blot. The level of
CD137 was measured by Flow Cytometry (FCM). RESULTS: (1) The mRNA and protein
expression of CD137 in VSMCs was significantly upregulated at 24 h after co
culture with TNF-alpha (10 ng/ml, all P < 0.05). (2) Compared with the control
group, the level of p-NF-kappaB p65 in cytoplasm and nucleus was significantly
increased (8.34 +/- 0.28 vs. 1, P < 0.05, and 2.64 +/- 0.42 vs. 1, P < 0.05)
while the level of IkappaB-alpha was reduced (1 vs. 2.70 +/- 0.28, P < 0.05)
after co-treatment with agonist-CD137 mAb, above effects were partly blocked by
adding specific NF-kappaB inhibitor PDTC (30 umol/L: 1.15 +/- 0.14 vs. 8.34 +/-
0.28, P < 0.05, and 2.09 +/- 0.12 vs. 2.64 +/- 0.42, P < 0.05, and 1.78 +/- 0.74
vs. 1, P < 0.05). (3) The mRNA (2.07 +/- 0.09 vs. 1, P < 0.05) and protein (1.75
+/- 0.07 vs. 1, P < 0.05) expression of NFATc1 was significantly upregulated by
agonist CD137mAb compared with the control group, and these effects could be
reversed by PDTC (1.15 +/- 0.07 vs. 2.07 +/- 0.09, P < 0.05, and 0.90 +/- 0.11
vs. 1.75 +/- 0.07, P < 0.05). CONCLUSION: CD137 signaling could affect the
NFATc1expression in VSMCs through NF-kappaB pathway.
PMID- 26420324
TI - [MicroRNA-182 modulates high glucose-induced cardiomyocyte hypertrophy via
targeting Rac1].
AB - OBJECTIVE: To investigate the role and signalling of microRNA(miR)-182 on
regulating high glucose-induced cardiomyocyte hypertrophy. METHODS: The
candidates of miR which might potentially be involved on targeting Rac1 were
predicted by applying bioinformatics analysis. The expression of all related
candidates miRs was verified by real-time reverse transcription-PCR (RT-PCR) in
cardiac tissues of db/db mice and db/m mice. Then the relationship between
candidates miR and Rac1 was investigated with Pearson relevant analysis. Neonatal
mice cardiomyocytes were cultured and divided into 2 groups: normal glucose group
and high glucose group. The level of selected miR and Rac1 in two groups was
detected by RT-PCR. Neonatal mice cardiomyocytes were then randomly divided into
4 groups: normal glucose group, selected microRNA mimics control group, high
glucose group, high glucose plus selected miR mimics control group. The
morphology of cardiomyocyte in each group was detected under light microscope.
Furthermore, Rac1, beta-MHC and alpha-SMA expressions were detected in cultured
cardiomyocyte treated by high glucose for 48 h after transfecting selected miR
mimics by RT-PCR and Western blot. RESULTS: A total of 6 miR candidates
potentially targeting Rac1 were screened by bioinformatics, which were miR-182,
miR-142-3p, miR-140, miR-101a, miR-429 and miR-200b. Among these candidates, miR
182 and miR-142-3p expression was significantly downregulated in cardiac tissues
of db/db mice compared with db/m controls (P < 0.05). MiR-182 was negatively
correlated with Rac1 by person analysis (r = -0.891 02). Downregulation of miR
182 and upregulation of Rac1, beta-MHC, alpha-SMA were found in high glucose
induced cardiomyocyte. After transfection of miR-182 mimics, hypertrophic changes
were significantly reduced and Rac1 as well beta-MHC expression was significantly
downregulated in cardiomyocyte incubated with high glucose. CONCLUSION: MiR-182
might be involved in the regulation of high glucose-induced myocardial
hypertrophy process via targeting Rac1.
PMID- 26420325
TI - [Telmisartan reduces retina vessel endothelial cell apoptosis via upregulating
retinal ACE2-Ang-(1-7)-Mas axis in spontaneous hypertensive rats].
AB - OBJECTIVE: To investigate the effects of angiotensin II (Ang II) antagonist
telmisartan on retina vessel endothelial cell apoptosis and its impact on the
ACE2-Ang-(1-7)-Mas axis in spontaneous hypertensive rats (SHR). METHODS: Thirty
six SHR 16 week-old were randomly divided into 3 groups (n = 12 each): SHR, SHRT
(telmisartan 10 mg . kg-1 . d-1 by gastric gavage) and SHRTA group (telmisartan
10 mg . kg-1 . d-1 by gastric gavage plus intravenous injection of A-779 0.5 mg .
kg-1 . d-1), twelve WKY rats served as normotensive control group. Systolic blood
pressure was measured at pre-treatment and 8 weeks later. After 8 weeks, rats
were sacrificed, the expression of ACE2 and Mas in retina were analyzed by qRT
PCR, Western blot and Immunohistochemistry, the Ang-(1-7) concentration in serum
was measured by ELISA. Specimens were obtained and stained by hematoxylin and
eosin, and the morphology of retina vessel was observed. Apoptosis of vessel
endothelial cells were determined by using terminal deoxynucleotidyl transferase
mediated dUTP nick end labeling method. RESULTS: The systolic blood pressure of
SHR, SHRT and SHRTA groups at baseline were significantly higher than age-matched
WKY group (all P < 0.01). Eight weeks later, the systolic blood pressure group
was significantly lower in SHRT group than in the SHR group (P < 0.01), this
effect was partly reversed in SHRTA group. The retinal ACE2 mRNA and protein
expression was significantly lower in SHR group than in WKY and SHRT groups (P <
0.01), which was similar between SHRT group and SHRTA group (P > 0.05). The
retinal Mas mRNA and protein expression were significantly lower in SHR group
compared to WKY and SHRT groups (all P < 0.01), which was significantly lower in
SHRTA group than in the SHRT group (P < 0.05). ELISA results showed that serum
Ang-(1-7) protein level was significantly lower in SHR group than in WKY group
and SHRT group (both P < 0.05), which was lower in SHRTA group compared to SHRT
group. Retinal vessel endothelial cell apoptosis was higher in SHR group than in
WKY group, which could be reduced by cotreatment with telmisartan and this
beneficial effect could be reversed by A-779. CONCLUSION: Telmisartan can reduce
retinal vessel endothelial cell apoptosis via upregulating the ACE2-Ang-(1-7)-Mas
axis.
PMID- 26420326
TI - [A case of transcatheter closure of inferior vena cava type atrial septal defect
with patent ductus arteriosus occlusion device guided by 3D printing technology].
PMID- 26420328
TI - [Simultaneous transcatheter closure of right coronary artery fistula and
percutaneous coronary intervention of left coronary artery disease: a case
report].
PMID- 26420327
TI - [Prior transcatheter aortic valve implantation evaluation with 3D printing
technology: a case report].
PMID- 26420329
TI - [Natural evolution of pericardial cyst in a 32-year-old male patient].
PMID- 26420330
TI - [Progress on transcatheter aortic valve implantation strategy for severe aortic
regurgitation].
PMID- 26420331
TI - [Value of fractional flow reserve measurements in patients with coronary artery
bifurcation lesions underwent percutaneous coronary intervention].
PMID- 26420332
TI - [Research advances on the therapeutic role of ezetimibe in atherosclerotic
cardiovascular diseases].
PMID- 26420333
TI - Clinical course and complications following diagnostic bronchoalveolar lavage in
critically ill mechanically ventilated patients.
AB - BACKGROUND: Flexible, fibreoptic bronchoscopy (FFB) and bronchoalveolar lavage
(BAL) have been used for diagnostic purposes in critically ill ventilated
patients. The additional diagnostic value compared to tracheal aspirations in
ventilator-associated pneumonia (VAP) has been questioned. Nevertheless, BAL can
provide extra information for the differential diagnosis of respiratory disease
and good antibiotic stewardship. These benefits should outweigh potential hazards
caused by the invasiveness of this diagnostic technique. The focus of the present
study was on the clinical course and complications of patients following BAL
procedures up to 24 h. METHODS: Hundred sixty-four FFB guided BAL procedures for
suspected pneumonia were analysed in an observational study. The clinical course
of patients was monitored by respiratory and haemodynamic data before BAL, 1 and
24 h after BAL. Complications were defined and registered. Factors associated
with complications were analysed by logistic regression. RESULTS: CLINICAL
COURSE: a decrease in average pO2/FiO2 ratio 1 h after BAL from 29 kPa (218 mmHg)
to 25 kPa (189 mmHg) (p < 0.05) was observed which fully recovered within 24 h.
Respiratory complications: the incidence of procedure related hypo-oxygenation
(SaO2 <= 88 %) and/or bronchospasm was 9 %; a decrease of >25 % PaO2/FiO2 ratio 1
h after BAL was found in 29 % of patients; no bleeding or pneumothorax were
registered. Haemodynamic complications: there were no cases of hypertension and
cardiac rhythm disturbances; haemodynamic instability within the first 24 h after
BAL was recorded in 22 %; this was correlated with a cardiovascular diagnosis at
admission (OR 2.9; 95 % CI 1.2 - 6.7) and the presence of cardiovascular co
morbidity (OR 3.5; 95 % CI 1.5 - 8.3). The incidence of bacteraemia was 7 %.
There was no case of procedure related death. DISCUSSION: Frequently occurring
haemodynamic and respiratory instability but no cases of cardiac rhythm
disturbances, bleeding, pneumothorax or procedure related death were attributable
to diagnostic FFB and BAL. The procedures should be conducted under careful
supervision by experienced physicians. Only a randomized controlled trial that
compares diagnostic FFB and BAL with a non-invasive strategy could ultimately
establish the safety profile and clinical utility of these procedures in
critically ill ventilated patients.
PMID- 26420334
TI - Randomised controlled trial of the effect of long-term selenium supplementation
on plasma cholesterol in an elderly Danish population.
AB - Although cross-sectional studies have shown a positive association between Se and
cholesterol concentrations, a recent randomised controlled trial in 501 elderly
UK individuals of relatively low-Se status found that Se supplementation for 6
months lowered total plasma cholesterol. The Danish PRECISE (PREvention of Cancer
by Intervention with Selenium) pilot study (ClinicalTrials.gov ID: NCT01819649)
was a 5-year randomised, double-blinded, placebo-controlled trial with four
groups (allocation ratio 1:1:1:1). Men and women aged 60-74 years (n 491) were
randomised to 100 (n 124), 200 (n 122) or 300 (n 119) MUg Se-enriched yeast or
matching placebo-yeast tablets (n 126) daily for 5 years. A total of 468
participants continued the study for 6 months and 361 participants, equally
distributed across treatment groups, continued for 5 years. Plasma samples were
analysed for total and HDL-cholesterol and for total Se concentrations at
baseline, 6 months and 5 years. The effect of different doses of Se
supplementation on plasma lipid and Se concentrations was estimated by using
linear mixed models. Plasma Se concentration increased significantly and dose
dependently in the intervention groups after 6 months and 5 years. Total
cholesterol decreased significantly both in the intervention groups and in the
placebo group after 6 months and 5 years, with small and nonsignificant
differences in changes in plasma concentration of total cholesterol, HDL
cholesterol, non-HDL-cholesterol and total:HDL-cholesterol ratio between
intervention and placebo groups. The effect of long-term supplementation with Se
on plasma cholesterol concentrations or its sub-fractions did not differ
significantly from placebo in this elderly population.
PMID- 26420337
TI - Rapid quantitative analysis of adulterant Lonicera species in preparations of
Lonicerae Japonicae Flos.
AB - Lonicerae Japonicae Flos is often adulterated with Lonicerae Flos, which is
derived from the other four Lonicera species, in both the crude drug and
Lonicerae Japonicae Flos preparations. We proposed a methodology for the
quantitative analysis of adulterant Lonicerae Flos in Lonicerae Japonicae Flos
preparations. Taking macranthoidins A, B, dipsacoside B (saponins), sweroside
(iridoids), and luteolin-7-O-d-glucoside (flavonoids) as markers, a method of
ultra high performance liquid chromatography with triple quadrupole mass
spectrometry was employed to determine their amounts in Lonicerae Flos, Lonicerae
Japonicae Flos, and Lonicerae Japonicae Flos preparations. The proportion of
adulterant Lonicerae Flos in Lonicerae Japonicae Flos preparations was estimated
based on the saponin contents of Lonicerae Japonicae Flos and Lonicerae Flos. All
analytes separated under isocratic elution in 12 min with acceptable linearity,
precision, repeatability, and accuracy. Lonicerae Japonicae Flos was easily
distinguished from Lonicerae Flos by the total amount of saponins (0.067 and >
45.8 mg/g for Lonicerae Japonicae Flos and Lonicerae Flos, respectively).
Eighteen of twenty one Lonicerae Japonicae Flos preparation samples were
adulterated with Lonicerae Flos in proportions of 11.3-100%. The developed ultra
high performance liquid chromatography with triple quadrupole mass spectrometry
method could be used for the identification of Lonicerae Japonicae Flos and the
four species of Lonicerae Flos and for the analysis of Lonicerae Japonicae Flos
preparations adulterated with Lonicerae Flos.
PMID- 26420336
TI - Next Generation of SiFAlin-Based TATE Derivatives for PET Imaging of SSTR
Positive Tumors: Influence of Molecular Design on In Vitro SSTR Binding and In
Vivo Pharmacokinetics.
AB - The Silicon-Fluoride-Acceptor (SiFA)-(18)F-labeling strategy has been shown
before to enable the straightforward and efficient (18)F-labeling of complex
biologically active substances such as proteins and peptides. Especially in the
case of peptides, the radiolabeling proceeds kit-like in short reaction times and
without the need of complex product workup. SiFA-derivatized, (18)F-labeled
Tyr(3)-octreotate (TATE) derivatives demonstrated, besides strong somatostatin
receptor (SSTR) binding, favorable in vivo pharmacokinetics as well as excellent
tumor visualization by PET imaging. In this study, we intended to determine the
influence of the underlying molecular design and used molecular scaffolds of
SiFAlin-TATE derivatives on SSTR binding as well as on the in vivo
pharmacokinetics of the resulting (18)F-labeled peptides. For this purpose, new
SiFAlin-(Asp)n-PEG1-TATE analogs (where n = 1-4) were synthesized, efficiently
radiolabeled with (18)F in a kit-like manner and obtained in radiochemical yields
of 70-80%, radiochemical purities of >=97%, and nonoptimized specific activities
of 20.1-45.2 GBq/MUmol within 20-25 min starting from 0.7-1.5 GBq of (18)F. In
the following, the radiotracer's lipophilicities and stabilities in human serum
were determined. Furthermore, the SSTR-specific binding affinities were evaluated
by a competitive displacement assay on SSTR-positive AR42J cells. The obtained in
vitro results support the assumption that aspartic acids are able to considerably
increase the radiotracer's hydrophilicity and that their number does not affect
the SSTR binding potential of the TATE derivatives. The most promising tracer
(18)F-SiFAlin-Asp3-PEG1-TATE [(18)F]6 (LogD = -1.23 +/- 0.03, IC50 = 20.7 +/- 2.5
nM) was further evaluated in vivo in AR42J tumor-bearing nude mice via PET/CT
imaging against the clinical gold standard (68)Ga-DOTATATE as well as the
previously developed SiFAlin-TATE derivative [(18)F]3. The results of these
evaluations showed that [(18)F]6-although showing very similar chemical and in
vitro properties to [(18)F]3-exhibits not only a slowed renal clearance compared
to [(18)F]3, but also a higher absolute tumor uptake compared to (68)Ga-DOTATATE,
and furthermore enables excellent tumor visualization with high image resolution.
These results emphasize the importance of systematic study of the influence of
molecular design and applied structure elements of peptidic radiotracers, as
these may considerably influence in vivo pharmacokinetics while not affecting
other parameters such as radiochemistry, lipophilicity, serum stability, or
receptor binding potential.
PMID- 26420335
TI - A pain-inducing centipede toxin targets the heat activation machinery of
nociceptor TRPV1.
AB - The capsaicin receptor TRPV1 ion channel is a polymodal nociceptor that responds
to heat with exquisite sensitivity through an unknown mechanism. Here we report
the identification of a novel toxin, RhTx, from the venom of the Chinese red
headed centipede that potently activates TRPV1 to produce excruciating pain. RhTx
is a 27-amino-acid small peptide that forms a compact polarized molecule with
very rapid binding kinetics and high affinity for TRPV1. We show that RhTx
targets the channel's heat activation machinery to cause powerful heat activation
at body temperature. The RhTx-TRPV1 interaction is mediated by the toxin's highly
charged C terminus, which associates tightly to the charge-rich outer pore region
of the channel where it can directly interact with the pore helix and turret.
These findings demonstrate that RhTx binding to the outer pore can induce TRPV1
heat activation, therefore providing crucial new structural information on the
heat activation machinery.
PMID- 26420339
TI - Infant Feeding Websites and Apps: A Systematic Assessment of Quality and Content.
AB - BACKGROUND: Internet websites and smartphone apps have become a popular resource
to guide parents in their children's feeding and nutrition. Given the diverse
range of websites and apps on infant feeding, the quality of information in these
resources should be assessed to identify whether consumers have access to
credible and reliable information. OBJECTIVE: This systematic analysis provides
perspectives on the information available about infant feeding on websites and
smartphone apps. METHODS: A systematic analysis was conducted to assess the
quality, comprehensibility, suitability, and readability of websites and apps on
infant feeding using a developed tool. Google and Bing were used to search for
websites from Australia, while the App Store for iOS and Google Play for Android
were used to search for apps. Specified key words including baby feeding, breast
feeding, formula feeding and introducing solids were used to assess websites and
apps addressing feeding advice. Criteria for assessing the accuracy of the
content were developed using the Australian Infant Feeding Guidelines. RESULTS: A
total of 600 websites and 2884 apps were screened, and 44 websites and 46 apps
met the selection criteria and were analyzed. Most of the websites (26/44) and
apps (43/46) were noncommercial, some websites (10/44) and 1 app were commercial
and there were 8 government websites; 2 apps had university endorsement. The
majority of the websites and apps were rated poor quality. There were two
websites that had 100% coverage of information compared to those rated as fair or
poor that had low coverage. Two-thirds of the websites (65%) and almost half of
the apps (47%) had a readability level above the 8th grade level. CONCLUSIONS:
The findings of this unique analysis highlight the potential for website and app
developers to merge user requirements with evidence-based content to ensure that
information on infant feeding is of high quality. There are currently no apps
available to consumers that address a variety of infant feeding topics. To keep
up with the rapid turnover of the evolving technology, health professionals need
to consider developing an app that will provide consumers with a credible and
reliable source of information about infant feeding, using quality assessment
tools and evidence-based content.
PMID- 26420343
TI - Electric control of topological phase transitions in Dirac semimetal thin films.
AB - Dirac semimetals host three-dimensional (3D) Dirac fermion states in the bulk of
crystalline solids, which can be viewed as 3D analogs of graphene. Owing to their
relativistic spectrum and unique topological character, these materials hold
great promise for fundamental-physics exploration and practical applications.
Particularly, they are expected to be ideal parent compounds for engineering
various other topological states of matter. In this report, we investigate the
possibility to induce and control the topological quantum spin Hall phase in a
Dirac semimetal thin film by using a vertical electric field. We show that
through the interplay between the quantum confinement effect and the field
induced coupling between sub-bands, the sub-band gap can be tuned and inverted.
During this process, the system undergoes a topological phase transition between
a trivial band insulator and a quantum spin Hall insulator. Consequently, one can
switch the topological edge channels on and off by purely electrical means,
making the system a promising platform for constructing topological field effect
transistors.
PMID- 26420338
TI - Emerging platforms using liquid biopsy to detect EGFR mutations in lung cancer.
AB - Advances in target therapies for lung cancer have enabled detection of gene
mutations, specifically those of EGFR. Assays largely depend on the acquisition
of tumor tissue biopsy, which is invasive and may not reflect the genomic profile
of the tumor at treatment due to tumor heterogeneity or changes that occur during
treatment through acquired resistance. Liquid biopsy, a blood test that detects
evidence of cancer cells or tumor DNA, has generated considerable interest for
its ability to detect EGFR mutations. However, its clinical application is
limited by complicated collection methods and the need for technique-dependent
platforms. Recently, simpler techniques for EGFR mutant detection in urine or
saliva samples have been developed. This review focuses on advances in liquid
biopsy and discusses its potential for clinical implementation in lung cancer.
PMID- 26420344
TI - Two new ent-kaurane-type diterpene glycosides from zucchini (Cucurbita pepo L.)
seeds.
AB - Two new ent-kaurane diterpene glycosides; 12alpha-(beta-d-glucopyranosyloxy)
7beta-hydroxykaurenolide (1) and 7beta-(beta-d-glucopyranosyloxy)-12alpha
hydroxykaurenolide (2), a new steroid; (24S)-stigmasta-7,22E,25-trien-3-one (12),
and known compounds (3-11, 13-14) were isolated from zucchini (Cucurbita pepo L.)
seeds. The absolute structures of 1 and 2 were determined by acid hydrolysis and
application of a modified Moscher's method. Furthermore, isolated compounds (1
14), and a derivative, 1a, were evaluated for their inhibitory effects on
macrophage activation by an inhibitory assay of nitric oxide (NO) production.
PMID- 26420345
TI - A 3-year follow-up after anterior colporrhaphy compared with collagen-coated
transvaginal mesh for anterior vaginal wall prolapse: a randomised controlled
trial.
AB - OBJECTIVE: To compare the 1-year (previously published) and 3-year objective and
subjective cure rates, and complications, related to the use of a collagen-coated
transvaginal mesh for anterior vaginal wall prolapse against a conventional
anterior repair. DESIGN: Randomised controlled study. SETTING: Six departments of
obstetrics and gynaecology in Norway, Sweden, Finland, and Denmark. POPULATION: A
total of 138 women, of 55 years of age or older, admitted for stage >=2 anterior
vaginal wall prolapse. METHODS: The women scheduled for primary anterior vaginal
wall prolapse surgery were randomised between conventional anterior colporrhaphy
and surgery with a collagen-coated prolene mesh. All patients were evaluated
using the Pelvic Organ Prolapse Quantification (POP-Q) assessment before and
after surgery. Symptoms related to pelvic organ prolapse were evaluated using the
Pelvic Floor Impact Questionnaire (PFIQ-7) and the Pelvic Floor Distress
Inventory (PFDI-20). MAIN OUTCOME MEASURES: Objective cure, defined as POP-Q
stage <2 prolapse at the 1- and 3-year follow-ups. Furthermore, mesh exposure and
dyspareunia were also recorded. RESULTS: In total, 138 patients (70 from the mesh
group versus 68 from the conventional anterior colporrhaphy group) out of 160
(86.3%) participated in the 3-year follow-up. POP-Q revealed an objective
anatomic cure for 88.1 and 91.4%, respectively, in the mesh group at the 1- and 3
year follow-ups, compared with 39.9 and 41.2% in the colporrhaphy group. No
difference between the groups was observed regarding PFIQ-7, PFDI-20, and Pelvic
Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) scores. The
number of mesh exposures did not change during the study period and all exposures
were minor. CONCLUSION: Our study demonstrates that although the objective
outcome was superior in the mesh group, the use of mesh had no impact on the
subjective outcome. TWEETABLE ABSTRACT: POP-Q deteriorates after anterior
prolapse surgery but remains stable in women with mesh implantation.
PMID- 26420346
TI - Twenty-One Novel EGFR Kinase Domain variants in Patients with Nonsmall Cell Lung
Cancer.
AB - Somatic sequence variants in the epidermal growth factor receptor (EGFR) kinase
domain are associated with sensitivity to tyrosine kinase inhibitors (TKIs) in
patients with nonsmall cell lung cancer (NSCLC). Patients exhibiting sequence
variants in this domain that produce kinase activity enhancement, are more likely
to benefit from TKIs than patients with EGFR wild-type disease. Although most
NSCLC EGFR-related alleles are concentrated in a few positions, established
protocols recommend sequencing EGFR exons 18-21. In this study, 21 novel somatic
variants belonging to such exons in adult Argentinean patients affected with
NSCLC are reported. Of these, 18 were single amino acid substitutions (SASs),
occurring alone or in combination with another genetic alteration (complex
cases), one was a short deletion, one was a short deletion-short insertion
combination, and one was a duplication. New variants and different combinations
of previously reported variants were also found. Moreover, two of the reported
SASs occurred in previously unreported positions of the EGFR kinase domain. In
order to characterize the new sequence variants, physicochemical, sequence and
conformational analyses were also performed. A better understanding of sequence
variants in NSCLC may facilitate the most appropriate treatment choice for this
complex disease.
PMID- 26420347
TI - Transfer of Copper from an Amyloid to a Natural Copper-Carrier Peptide with a
Specific Mediating Ligand.
AB - The oxidative stress that arises from the catalytic reduction of dioxygen by
Cu(II/I)-loaded amyloids is the major pathway for neuron death that occurs in
Alzheimer's disease. In this work, we show that bis-8(aminoquinoline) ligands,
copper(II) specific chelators, are able to catalytically extract Cu(II) from Cu
Abeta1-16 and then completely release Cu(I) in the presence of glutathione to
provide a Cu(I)-glutathione complex, a biological intermediate that is able to
deliver copper to apo forms of copper-protein complexes. These data demonstrate
that bis-8(aminoquinolines) can perform the transfer of copper ions from the
pathological Cu-amyloid complexes to regular copper-protein complexes. These
copper-specific ligands assist GSH to recycle Cu(I) in an AD brain and
consequently slow down oxidative damage that is due to copper dysregulation in
Alzheimer's disease. Under the same conditions, we have shown that the copper
complex of PBT2, a mono(8-hydroxyquinoline) previously used as a drug candidate,
does not efficiently release copper in the presence of GSH. In addition, we
report that GSH itself was unable to fully abstract copper ions from Cu-beta
amyloid complexes.
PMID- 26420348
TI - The pattern of CD44 and matrix metalloproteinase 9 expression is a useful
predictor of ulcerative colitis-associated dysplasia and neoplasia.
AB - Ulcerative colitis (UC)-associated neoplasia presumably evolves through a chronic
inflammation-dysplasia-adenocarcinoma sequence in which a corporation of several
factors takes place. The grade of dysplasia is important in further development
of colorectal cancer. CD44 is a cell adhesion molecule and acts as a docking
receptor for matrix metalloproteinase 9 (MMP-9). The aims of this study are to
assess UC-associated dysplasia and to distinguish regenerative changes from
premalignant ones through detecting pattern of CD44 and MMP-9 expression in
different UC lesions. Fifty-four samples of UC and UC-associated carcinoma were
collected and examined for the immunohistochemical expression of CD44 and MMP-9
in the colon mucosa. Correlation between their expression and the severity of
dysplasia were also statistically analyzed. Homogenous membranous staining
pattern of CD44 was detected in all cases of regenerative atypia (negative for
dysplasia) and most of indefinite for dysplasia (IND) cases, whereas most
dysplastic (low-grade and high-grade dysplasia) cases showed irregular staining
pattern. CD44 expression pattern was significantly correlated with grade of
dysplasia in UC (P = .0001); on the other hand, MMP-9 expression was
significantly increased in the dysplastic and neoplastic cases than in
nondysplastic cases (regenerative atypia and IND) (P = .0001). Significant
correlation was found between irregular CD44 staining pattern and MMP-9
expression (P = .0001). Irregular staining pattern of CD44 together with
increased MMP-9 expression in UC-associated dysplasia predicts advanced disease
and aids in the differentiation of regenerative atypia from UC-associated
dysplasia as well as grading of IND cases.
PMID- 26420349
TI - Use of ultrasmall superparamagnetic iron oxide particles for imaging carotid
atherosclerosis.
AB - Based on the results of histopathological studies, inflammation within
atherosclerotic tissue is now widely accepted as a key determinant of the disease
process. Conventional imaging methods can highlight the location and degree of
luminal stenosis but not the inflammatory activity of the plaque. Iron oxide
based MRI contrast media particularly ultrasmall supermagnetic particles of iron
oxide have shown potential in assessing atheromatous plaque inflammation and in
determining efficacy of antiatherosclerosis pharmacological treatments. In this
paper, we review current data on the use of ultrasmall superparamagnetic iron
oxides in atherosclerosis imaging with focus on ferumoxtran-10 and ferumoxytol.
The basic chemistry, pharmacokinetics and dynamics, potential applications,
limitations and future perspectives of these contrast media nanoparticles are
discussed.
PMID- 26420350
TI - Effect of the type of silage on milk yield, intake and rumen metabolism of dairy
cows grazing swards with low herbage mass.
AB - The aim of this study was to evaluate the effect of herbage allowance (HA) and
type of silage supplemented (TS) on milk yield, dry matter intake (DMI) and
metabolism of dairy cows in early lactation. Thirty-six Holstein-Friesian dairy
cows were allocated to four treatments derived from an arrangement of two HA (LHA
= 17 or HHA = 25 kg of DM/cow/day) and two TS (grass (GS) or maize (MS)). Herbage
allowance had no effect on DMI or milk yield. Rumen pH and NH3 -N concentration
were not affected by HA. The efficiency of microbial protein synthesis in the
rumen (microbial protein (MP)) was affected by HA with 21.5 and 23.9 g microbial
nitrogen per kg ruminal digestible organic matter for LHA and HHA, respectively
(P < 0.05). Supplementation with MS showed higher values of milk yield by 2.4
kg/cow/day (P < 0.001), milk protein content by 0.10 % (P < 0.023) and herbage
DMI by 2.2 kg/cow/day, and showed lower values for milk urea compared to GS (P <
0.001). The former results suggest that TS had a greater effect on milk yield,
total feed intake and energy intake than increase in herbage allowance; however,
increase in HA had greater effects on MP than TS.
PMID- 26420351
TI - Effects of a feeding intervention in patients with Alzheimer's disease and
dysphagia.
AB - AIMS AND OBJECTIVES: This study aimed to investigate the effects of a feeding
intervention in patients with Alzheimer's disease with dysphagia. BACKGROUND: In
patients with Alzheimer's disease, inadequate food and fluid intake can result in
malnutrition, dehydration and increased morbidity and mortality. Patients may
lose self-care abilities such as self-feeding. DESIGN: A prospective cohort
study. METHODS: A three-month self-control feeding intervention was conducted
prospectively in 30 nursing home residents with Alzheimer's disease with
dysphagia. Pre- and post-intervention measures included the Kubota water swallow
test, type and amount of food intake and assessment of nutritional status by
triceps skinfold thickness, upper arm circumference, serum albumin and
haemoglobin. We used the Edinburgh Feeding Evaluation in Dementia scale to
evaluate eating compliance and the Mini- Mental State Examination to evaluate
cognitive function. Pre- and post-intervention results were compared to evaluate
the effects of nursing intervention. RESULTS: Patients' eating/feeding abilities
improved overall, including significantly increased food intake (p < 0.001),
decreased levels on the Kubota water swallow test (p < 0.001) and significant
differences in skinfold thickness, arm circumference, serum albumin and
haemoglobin (all p < 0.01), indicating improved nutritional status. Edinburgh
Feeding Evaluation in Dementia scale scores decreased significantly, showing
improved eating compliance. No changes were noted in cognition post-intervention.
Among 22 patients who initially required feeding, five patients resumed self
feeding after the intervention (p = 0.06). CONCLUSIONS: Results of this study
show that a feeding intervention can improve food intake, eating compliance and
nutritional status in patients with Alzheimer's disease with dysphagia and
prevent further decline in swallowing function. RELEVANCE TO CLINICAL PRACTICE:
The significant improvement in eating/feeding measures suggest that this feeding
intervention model could be developed as a feeding skills programme to improve
both the eating/feeding care by nursing staff and the eating/feeding abilities
and nutritional status of Alzheimer's disease patients.
PMID- 26420352
TI - Mothers' group participation: associations with social capital, social support
and mental well-being.
AB - AIM: To investigate the relationships between participation in mothers' groups
and social capital, social support and mental well-being measures for mothers
whose oldest child was 0-5 years. BACKGROUND: Evaluations of facilitated mothers'
groups have found positive benefits for information sharing and support. Mothers'
groups often continue as parent-led groups; however, little is known about the
potential benefits of ongoing participation compared with non-participation.
DESIGN: Cross-sectional survey. METHODS: Data were collected through a survey
from March 2013-January 2014 in Perth, Western Australia. The data from a
subgroup of mothers (N = 313) whose oldest child was 0-5 years of age were
analysed using multivariable regression. Participation in mothers' groups in the
previous 12 months was investigated for associations with social capital
{Neighbourhood Cohesion Index (NCI); Families, Social Capital and Citizenship
Survey (FSCCS) and Reciprocity}; social support {Medical Outcomes Study-Social
Support Survey (MOS-SSS) and Parent Support Outside Home Scale (PSOHS)}; and
mental well-being {Warwick Edinburgh Mental Well-Being Scale (WEMWBS)}.
Participation was measured as three groups - locally, outside area of residence
and non-participation. RESULTS: Mothers who participated in mothers' groups
locally scored significantly higher than those who had not participated in
mothers' group for 'social capital' (NCI, FSCCS, Reciprocity), 'social support'
(MOS-SSS, PSOHS) and 'mental well-being' (WEMWBS). Mothers who participated in
mothers' group outside the area scored significantly higher than those who had
not participated in mothers' groups for one measure of 'social support' (PSOHS).
CONCLUSIONS: Participation in mothers' group locally may provide support and
social capital benefits for mothers of children aged 0-5 years, which may
influence mental well-being.
PMID- 26420353
TI - Histone Acetyltransferase GCN5 Regulates Osteogenic Differentiation of
Mesenchymal Stem Cells by Inhibiting NF-kappaB.
AB - As the most well-studied histone acetyltransferase (HAT) in yeast and mammals,
general control nonderepressible 5 (GCN5) was documented to play essential roles
in various developmental processes. However, little is known about its role in
osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we detected
the critical function of GCN5 in osteogenic commitment of MSCs. In this role, the
HAT activity of GCN5 was not required. Mechanistically, GCN5 repressed nuclear
factor kappa B (NF-kappaB)-dependent transcription and inhibited the NF-kappaB
signaling pathway. The impaired osteogenic differentiation by GCN5 knockdown was
blocked by inhibition of NF-kappaB. Most importantly, the expression of GCN5 was
decreased significantly in the bone tissue sections of ovariectomized mice or
aged mice. Collectively, these results may point to the GCN5-NF-kappaB pathway as
a novel potential molecular target for stem cell mediated regenerative medicine
and the treatment of metabolic bone diseases such as osteoporosis.
PMID- 26420354
TI - Deficiency in apolipoprotein A-I ablates the pharmacological effects of metformin
on plasma glucose homeostasis and hepatic lipid deposition.
AB - Recently, we showed that deficiency in apolipoprotein A-I (ApoA-I) sensitizes
mice to diet-induced obesity, glucose intolerance and NAFLD. Here we investigated
the potential involvement of ApoA-I in the pharmacological effects of metformin
on glucose intolerance and NAFLD development. Groups of apoa1-deficient (apoa1(-/
)) and C57BL/6 mice fed western-type diet were either treated with a daily dose
of 300 mg/kg metformin for 18 weeks or left untreated for the same period. Then,
histological and biochemical analyses were performed. Metformin treatment led to
a comparable reduction in plasma insulin levels in both C57BL/6 and apoa1(-/-)
mice following intraperitoneal glucose tolerance test. However, only metformin
treated C57BL/6 mice maintained sufficient peripheral insulin sensitivity to
effectively clear glucose following the challenge, as indicated by a [(3)H]-2
deoxy-D-glucose uptake assay in isolated soleus muscle. Similarly, deficiency in
ApoA-I ablated the effect of metformin on hepatic lipid deposition and NAFLD
development. Gene expression analysis indicated that the effects of ApoA-I on
metformin treatment may be independent of adenosine monophosphate-activated
protein kinase (AMPK) activation and de novo lipogenesis. Interestingly,
metformin treatment reduced mitochondrial oxidative phosphorylation function only
in apoa1(-/-) mice. Our data show that the role of ApoA-I in diabetes extends to
the modulation of the pharmacological actions of metformin, a common drug for the
treatment of type 2 diabetes.
PMID- 26420355
TI - Impaired endothelial calcium signaling is responsible for the defective dilation
of mesenteric resistance arteries from db/db mice to acetylcholine.
AB - We aimed at assessing the role of endothelial cell calcium for the endothelial
dysfunction of mesenteric resistance arteries of db/db mice (a model of type 2
diabetes) and determine whether treatment with sulfaphenazole, improves
endothelial calcium signaling and function. Pressure myography was used to study
acetylcholine (ACh) -induced vasodilation. Intracellular calcium ([Ca(2+)]i)
transients was measured by confocal laser scanning microscopy and smooth muscle
membrane potential with sharp microelectrodes. The impaired dilation to ACh
observed in mesenteric resistance arteries from db/db mice was improved by
treatment of the mice with sulfaphenazole for 8 weeks. The impaired dilation to
ACh was associated with decreased endothelial [Ca(2+)]i and smooth muscle
hyperpolarization. Sulfaphenazole applied in vitro improved endothelial mediated
dilation of arteries from db/db mice both in the absence and the presence of
inhibitors of nitric oxide and cyclooxygenase. Sulfaphenazole also increased the
percentage of endothelial cells with ACh induced increases of [Ca(2+)]i. The
study shows that impaired endothelial [Ca(2+)]i control can explain the reduced
endothelial function in arteries from diabetic mice and that sulfaphenazole
treatment improves endothelial [Ca(2+)]i responses to ACh and consequently
endothelium-dependent vasodilation. These observations provide mechanistic
insight into endothelial dysfunction in diabetes.
PMID- 26420356
TI - Beneficial effect of magnesium lithospermate B on cerebral ischemia-reperfusion
injury in rats involves the regulation of miR-107/glutamate transporter 1
pathway.
AB - Recent studies uncovered that glutamate accumulation following cerebral ischemia
reperfusion (I/R) was related to the dysfunction of miR-107/glutamate transporter
1(GLT-1) pathway and magnesium lithospermate B (MLB) possesses the
pharmacological activity of anti-excitotoxicity. This study aims to explore
whether MLB is able to protect rat brain from excitatory neurotoxicity during I/R
by modulating miR-107/GLT-1 pathway. Rats were subjected to 2h of cerebral
ischemia following by 24h of reperfusion to establish an I/R injury model, which
showed an increase in neurological deficit score, infarct volume and cellular
apoptosis concomitant with glutamate accumulation, miR-107 elevation and GLT-1
down-regulation. Administration of MLB reduced I/R-induced cerebral injury
accompanied by a reverse in glutamate accumulation, miR-107 and GLT-1 expression.
Next, we examined the association of MLB with miR-107/GLT-1 pathway in a nerve
cell hypoxia/reoxygenation (H/R) injury model. H/R treatment increased the nerve
cells apoptosis concomitant with glutamate accumulation and miR-107 elevation,
and suppressed GLT-1 expression, mimicking our in vivo findings. All these
effects were reversed in the presence of MLB, confirming a strong correlation
between MLB and miR-107/GLT-1 pathway. Based on these observations, we conclude
that MLB is able to protect the rat brain from excitatory neurotoxicity during
I/R through the regulation of miR-107/GLT-1 pathway.
PMID- 26420361
TI - Depression: Evolutionary New Neural Circuitries Are Still Adjusting for
Cognition.
AB - Depression can be both normal and abnormal, and the balance of its expression
determines the behavioral outcome/diagnosis. It is a complex pathophysiology
based on a heterogeneous syndrome whose etiology is diverse as well. Within the
context of a central nervous system, the nervous system blueprint can be found in
single cells (sensory, motor, and integrative processes). These consolidated
functions provide for novel coping strategies for survival. The maintenance and
evolvement of this system into a central nervous system is based on conserving
these functions, including chemical messengers and functionality in having
specific cells medi-ate these primordial functions. Additionally, this neural
coping strategy provides advantages for DNA. Thus, with different neural cells at
work, pathways/networks would evolve, producing more complex behaviors and become
a very critical phenomenon for future advances. This evolvement has taken over 1
billion years to de-velop. In so doing, as with any new programming (e.g.,
cognition), errors will occur. Given the widespread qual-ities of depression, it
is surmised that this abnormality, and other psychiatric disorders, may emerge
due to in-herent neural weaknesses related to cognition being a recent
evolutionary development.
PMID- 26420362
TI - High volumetric uptake of ammonia using Cu-MOF-74/Cu-CPO-27.
AB - Cu-MOF-74 (also known as Cu-CPO-27) was identified as a sorbent having one of the
highest densities of Cu(ii) sites per unit volume. Given that Cu(ii) in the
framework can be thermally activated to yield a five-coordinate Cu(ii) species,
we identified this MOF as a potential candidate for maximal volumetric uptake of
ammonia. To that end, the kinetic breakthrough of ammonia in Cu-MOF-74/Cu-CPO-27
was examined under both dry and humid conditions. Under dry conditions the MOF
exhibited a respectable performance (2.6 vs. 2.9 NH3 per nm(3) for the current
record holder HKUST-1), and under 80% relative humidity, the MOF outperformed
HKUST-1 (5.9 vs. 3.9 NH3 per nm(3), respectively).
PMID- 26420363
TI - The Role of Flow-Independent Exhaled Nitric Oxide Parameters in the Assessment of
Airway Diseases.
AB - Nitric oxide (NO), the first gas known to act as a biological messenger, is one
of the most widely studied free radical/gas in medicine, both for its biological
function and therapeutic applications. The measurement of endogenous NO in
exhaled air is widely used in the evaluation of lung disorders. Partitioning of
exhaled nitric oxide (eNO) is of increasing interest because of the additional
information about lung pathology and distal lung inflammation that can be
obtained. Specifically, measuring exhaled NO at multiple flow rates allows
assessment of the flow-independent NO parameters: alveolar NO concentration
(CalvNO), bronchial NO flux (JNO), bronchial wall NO concentration (CWNO), and
bronchial diffusing capacity of NO (DNO). Several studies have reported that
there were different patterns of those parameters in different airway diseases
and/or in different severities of the same disease, mostly in asthma.
Specifically, while JNO seems to provide the same information as FeNO50, alveolar
NO concentration appears to be an independent parameter that is putatively
associated with increased distal lung inflammation and more severe disease.
However, despite much research interest in partitioning exhaled NO, clinical
usefulness has yet to be established.
PMID- 26420364
TI - Vascular Biomarkers in Asthma and COPD.
AB - Bronchial asthma and chronic obstructive pulmonary disease (COPD) remain a global
health problem with significant morbidity and mortality. The changes in bronchial
microvasculature that occurin asthma and COPD contribute to airway wall
remodeling. Angiogenesis seems to be more prevalent in asthma and vasodilatation
seemsmore relevant in COPD while vascular leak is present in both diseases.
Recently, there has been increased interest in the vascular component of airway
remodeling in chronic bronchial inflammation of asthma and COPD although its role
in the progression of the diseases has not been fully elucidated. Various cells
andmediators are involved in the vascular remodeling in asthma and COPD while
proinflammatory cytokines and growth factors exert angiogenic and antiangiogenic
effects. Vascular endothelial growth factor (VEGF) is a key regulator of blood
vessel growth mainly in asthma but also in COPD. In asthmatic airways VEGF
promotes proliferation and differentiation of endothelial cells and induces
vascular leakage and permeability. It has also been involved in enhanced allergic
sensitization, upregulated subsequent T-helper-2 type inflammatory responses,
chemotaxis for monocytes and eosinophils, and airway oedema. Impaired VEGF
signaling has been associated with emphysema in animal models. Studies on lung
biopsies have shown a decreasing effect of anti-asthma drugs to the vascular
component of airway remodeling. There is less available evidence on the effect of
the currently used drugs on airway microvascular network in COPD. This review
article explores the current knowledge regarding vascular biomarkers in asthma
and COPD as well as the therapeutic implications of these mediators.
PMID- 26420365
TI - Biomarkers in the Evaluation and Management of Idiopathic Pulmonary Fibrosis.
AB - Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, debilitating
disease of unknown etiology and a median survival from diagnosis of 3-5 years.
Despite extensive research efforts, its etiology in humans still remains largely
unknown, and no curative drug therapies are available. With a gradually
increasing worldwide incidence, IPF still presents a major challenge in clinical
research due to its appreciable heterogeneity among individual patients in
disease course and the lack of easily reproducible surrogate markers for patient
relevant outcomes. Currently clinicians and researchers apply a panel of
functional, radiological and histopathological indices to stratify patients into
distinct phenotypic patterns of disease progression. However, none of these
indicators can reliably predict not only treatment responsiveness but more
importantly disease behavior, thus allowing clinicians to promptly apply
aggressive therapeutic approaches to prevent or ameliorate acute exacerbation.
Furthermore, on the contrary to molecular biomarkers, physiologic prognosticators
provide no insights into disease mechanism and thus are unlikely to identify
distinct molecular phenotypes of the disease. In the dawn of the "fibromics" era
the need for disease stratification based on molecular phenotypes and
implementation of personalized medicine therapeutic approaches is still unmet.
Molecular biomarkers lie in the core of personalized medicine and therefore
represent the main focus of this review article. Limitations that hamper their
widespread clinical applicability along with future perspectives on how to
address these major caveats and launch IPF biomarkers to the same trajectory as
to tumor biomarkers in oncology are also discussed.
PMID- 26420366
TI - Phenotyping and Endotyping Asthma Based on Biomarkers.
AB - Asthma is a chronic inflammatory airways disorder mainly characterized by
heterogeneity. A phenotype is defined as a group of patients that present similar
clinically observable characteristics, without establishing a direct etiologic
relationship with a distinct pathophysiologic mechanism. An endotype, on the
other hand, describes a subgroup that shares the same pathophysiologic processes
that lead to the development, the progression and the presentation of a disease.
A biomarker has been defined as a characteristic that is objectively measured and
evaluated as an indicator of normal biological processes, pathogenic processes or
pharmacologic responses to a therapeutic intervention. Several inflammatory
phenotypes have been identified by the use of biomarkers. Most of them are based
on the predominant type of cells in different biological fluids with sputum to be
remained the most representative one. Eosinophilia represents the major
characteristic of what we called classic atopic asthma. This particular phenotype
usually responds well to corticosteroids, except for a small subgroup of severe
asthma where even in the presence of eosinophils the ICS seem to have a less
responsive role. Neutrophilic phenotype driven by the presence of neutrophils
shows inadequate response to corticosteroid treatment, even in mild asthma. The
major approach in order to define an endotype is driven by three main parameters.
The statistical clustering approach, use of advanced statistical mathematics to
create distinct patient clusters, the specific targeted immune therapies and
finally the application of omics' approach. Both phenotypes and endotypes are
trying to clarify mechanisms and processes that driven the complexity of asthma.
Both concepts could identify approaches which could establish new targeted to
specific biomarkers treatment therapies/strategies.
PMID- 26420367
TI - Surfactant Proteins in Smoking-Related Lung Disease.
AB - Pulmonary surfactant is a highly surface-active mixture of proteins and lipids
that is synthesized and secreted in the alveoli by type II epithelial cells and
is found in the fluid lining the alveolar surface. The protein part of surfactant
constitutes two hydrophilic proteins (SP-A and SP-D) that regulate surfactant
metabolism and have immunologic functions, and two hydrophobic proteins (SP-B and
SP-C), which play a direct role in the organization of the surfactant structure
in the interphase and in the stabilization of the lipid layers during the
respiratory cycle. Several studies have shown that cigarette smoke seems to
affect, in several ways, both surfactant homeostasis and function. The
alterations in surfactants' biophysical properties caused by cigarette smoking,
contribute to the development of several smoking related lung diseases. In this
review we provide information on biochemical and physiological aspects of the
pulmonary surfactant and on its possible association with the development of two
major chronic diseases of the lung known to be related to smoking, i.e. chronic
obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).
Additional information on the possible role of surfactant protein alterations
and/or dysfunction in the combination of these two conditions, recently described
as combined pulmonary fibrosis and emphysema (CPFE) are also provided.
PMID- 26420368
TI - Methodological Issues and Possible Clinical Implications for Exhaled Breath
Condensate pH in Asthma.
AB - Exhaled breath condensate (EBC) pH is a commonly studied biomarker which
represents the acidity of the whole airway tract, including the lower and upper
airways as well as oral cavity. Because neat, unprocessed EBC pH can be affected
by environmental and end-tidal carbon dioxide, two further reproducible
techniques have been developed to measure condensate acidity with several
methodological, pathophysiological and environmental factors which may influence
EBC pH. Airway acidification may contribute to various pathological features of
asthma, therefore EBC pH may be a non-invasive, but unspecific clinical biomarker
of this disorder. This review summarises the current knowledge on EBC pH in
asthma focusing on methodological aspects and possible clinical applications.
PMID- 26420369
TI - Cardiac Biomarkers in the Identification of Future Risk in Chronic Obstructive
Pulmonary Disease.
AB - Chronic obstructive pulmonary disease (COPD) is a common and disabling disease
and the third leading cause of global mortality behind ischemic heart disease and
stroke. Acute exacerbations of COPD accelerate lung function decline affecting
the quality of life of COPD patients and moreover, remain the major contributors
to morbidity and mortality of these patients. Cardiovascular comorbidities are
prevalent in COPD patients and of great importance since they have a negative
impact on patients' health status. During the past few years there is an
increasing interest in potential molecules that can be measured accurately and
reproducibly and that can be used in COPD as biomarkers to predict clinical
important outcomes such as exacerbations, hospitalizations and mortality. Such
molecules have been successfully used in cardiovascular diseases and therefore,
cardiac biomarkers have attracted attention for their potential use in COPD. The
present review summarizes the available evidence for the use of the most
important cardiac biomarkers in the evaluation of COPD severity, outcomes and
management.
PMID- 26420370
TI - Incidental Diagnosis of Asymptomatic Non-Small-Cell Lung Cancer: A Registry-Based
Analysis.
AB - INTRODUCTION: Clinical manifestation of non-small-cell lung cancer (NSCLC) mainly
occurs at advanced stages. Thus, the scientific community is evaluating different
screening programs in high-risk patients to detect NSCLC at an earlier stage to
improve survival. However, up to now patient selection and modalities have been
discussed controversially. In this analysis we aimed to focus on asymptomatic
NSCLC patients, whose disease was detected coincidentally and to elaborate the
significance and effect of incidentally detected NSCLC on survival. PATIENTS AND
METHODS: Medical files of 1279 consecutive NSCLC patients diagnosed between 2001
and 2009 were retrospectively analyzed. Incidentally detected asymptomatic NSCLC
patients were compared with patients with tumor-specific symptoms. RESULTS: In
117 of 1279 patients an asymptomatic diagnosis was ascertained by coincidence
(9.1%). A smoking history of >= 30 pack-years was documented in 41 (58.6%) of 70
evaluable patients with incidentally detected NSCLC. Patients with incidentally
diagnosed NSCLC were characterized by lower stages at diagnosis, a better
performance status, and a higher proportion of previous or present other
malignancies. Overall survival (OS) was significantly superior in patients with
an asymptomatic diagnosis compared with patients with symptoms (median OS, 38.9
months vs. 16.1 months; P < .001). In a Cox proportional hazard model, incidental
diagnosis proved to be an independent prognostic factor with regard to OS.
CONCLUSION: Our findings point to the advantage of asymptomatic detection of
NSCLC and might underline the benefit of screening programs. Further research on
the detection of lung cancer in asymptomatic patients outside of existing
screening criteria is warranted.
PMID- 26420371
TI - Mesenchymal stem cells stabilize the blood-brain barrier through regulation of
astrocytes.
AB - INTRODUCTION: The blood-brain barrier (BBB) protects the brain against
potentially neurotoxic molecules in the circulation, and loss of its integrity
may contribute to disease progression in neurodegenerative conditions. Recently,
the active role of reactive astrocytes in BBB disruption has become evident in
the inflamed brain. In the present study, we investigated whether mesenchymal
stem cell (MSC) treatment might modulate reactive astrocytes and thus stabilize
BBB integrity through vascular endothelial growth factor A (VEGF-A) signaling in
inflammatory conditions. METHODS: For the inflamed brain, we injected LPS using a
stereotaxic apparatus and MSCs were injected into the tail vein. At 6 hours and 7
days after LPS injection, we analyzed modulatory effects of MSCs on the change of
BBB permeability through VEGF-A signaling using immunochemistry and western blot.
To determine the effects of MSCs on VEGF-A-related signaling in cellular system,
we had used endothelial cells treated with VEGF-A and co-cultured astrocyte and
BV 2 cells treated with lipopolysaccharide (LPS) and then these cells were co
cultured with MSCs. RESULTS: In LPS-treated rats, MSCs restored Evans blue
infiltration and the number of endothelial-barrier antigen (EBA) and P
glycoprotein (p-gp)-expressing cells, which were significantly altered in LPS
treated animals. Additionally, MSC administration following LPS treatment
markedly increased the density of astrocytic filaments around vessels and
reversed LPS-induced elevations in VEGF-A levels as well as endothelial nitric
oxide synthase (eNOS)-dependent downregulation of tight junction proteins in the
endothelium. Consequently, MSC treatment reduced neutrophil infiltration and
enhanced survival of midbrain dopaminergic neurons in LPS-treated animals. In
cellular system, MSC treatment led to a significant reversion of VEGF-A-induced
eNOS and tight junction protein expression in endothelial cells, which led to
increased EBA expressing cells. Additionally, MSC treatment significantly
attenuated LPS-induced increased expressions of IL-1beta in microglia and VEGF-A
in astrocytes with an increase in IL-10 levels. CONCLUSION: The present study
indicated that MSCs may stabilize BBB permeability by modulating astrocytic
endfeet and VEGF-A signaling, which may be relevant to the treatment of
Parkinsonian diseases as a candidate for disease modifying therapeutics.
PMID- 26420373
TI - Bottom-up, hard template and scalable approaches toward designing nanostructured
Li2S for high performance lithium sulfur batteries.
AB - Li2S with a high theoretical capacity of 1166 mA h g(-1) and the capability to
pair with lithium free anodes has drawn much attention for lithium sulfur (Li-S)
battery applications. However, the fast battery decay and the low capacity
retention due to dissolution of intermediate polysulfides in electrolytes limit
its development. Designing a nanosized and nanostructured host for Li2S through
facile techniques is one of the ways to alleviate the dissolution and improve Li
S battery performance; nevertheless, it is technically difficult to synthesize
nanosized and nanostructured hosts for Li2S because Li2S is highly sensitive to
moisture and oxygen. Herein, a novel technique, i.e., a bottom-up, hard template
and scalable method, is proposed to engineer nanoLi2S composites with core-shell
structures as cathodes of Li-S batteries. The size of the as-prepared
nanostructured Li2S is around 100 nm. With the assistance of FETEM, HRTEM and
EFTEM elemental mapping, an excellent core-shell structure has been confirmed and
the outside carbon shell has a thickness of 20-50 nm, effectively retarding
polysulfide outflow and dissolution. A high initial capacity of 915 mA h g(-1) at
0.2 C has been achieved upon electrochemical cycling and the battery still has
exceptional capacity retention after prolonged 200 cycles with a limited decay of
0.18% per cycle. Also, at 0.5 C the electrode exhibits 60% capacity retention
with a long life of 300 cycles. We attribute these good performances to the nano
architecture constructed by the novel and facile method.
PMID- 26420372
TI - Characteristics of Travelers to Asia Requiring Multidose Vaccine Schedules:
Japanese Encephalitis and Rabies Prevention.
AB - BACKGROUND: Japanese encephalitis (JE) and rabies are serious vaccine preventable
diseases which are an important consideration for travelers to Asia. METHODS:
Five Boston-area travel clinics collected demographic data, trip information, and
interventions for travelers to Asia seen at pre-travel consultations from March
1, 2008, through July 31, 2010. We evaluated travelers for proportion vaccinated
for JE and rabies, those traveling for >1 month, and whether travelers had
adequate time to complete the JE series (clinic visit >=28 days before departure)
and rabies pre-exposure prophylaxis (clinic visit >=21 days before departure).
RESULTS: Among 15,440 travelers from five Boston Area Travel Medicine Network
travel clinics, Asia was the most common destination region, visited by 5,582
(36%) of travelers. Among these travelers, 4,810 (86%) planned to travel to only
one Asian subregion. Median trip duration was 17 days, with more than 20%
traveling for >1 month. The most common destinations were South (41%), Southeast
(26%), and East (23%) Asia. Of those traveling to South, Southeast, or East Asia,
over one-third with trips >1 month had insufficient time to complete a series for
either JE or rabies vaccine. Overall, only 10% of travelers were vaccinated (past
and pre-travel visit) for either JE or rabies, with lowest percentages among
travelers visiting friends and relatives. Most travelers received advice on
vector precautions (96%) and rabies prevention, which included avoiding animal
contact, washing wounds, and obtaining appropriate post-exposure prophylaxis
(88%). CONCLUSION: Given the insufficient time for completion and relatively low
vaccination rates, greater awareness of earlier pre-travel consultations, at
least 4-6 weeks before travel, and accurate risk assessment for travelers are
important. Effective counseling about vector avoidance, rabies, and animal bite
prevention and management remains critical.
PMID- 26420374
TI - The association of sleep-disordered breathing with high cerebral pulsatility
might not be related to diffuse small vessel disease. A pilot study.
AB - BACKGROUND: In a population-based sampling study conducted in community-dwelling
older adults living in rural Ecuador, we aimed to assess the relation among sleep
disordered breathing, cerebral pulsatility index, and diffuse small vessel
disease. METHODS: Of 25 participants, 9 (36%) had moderate-to-severe sleep
disordered breathing, characterized by an apnea/hypopnea index >=15 per hour, and
10 (40%) had moderate-to-severe white matter hyperintensities, graded according
to the modified Fazekas scale. Mean (SD) pulsatility index in the middle cerebral
artery was 1.18 (0.19) and positively correlated with the apnea/hypopnea index (R
= .445, P = .03, [Pearson's correlation coefficient]). The middle cerebral artery
pulsatility index was increased in persons with moderate-to-severe sleep
disordered breathing compared with persons who had none-to-mild sleep-disordered
breathing (mean [SD] 1.11 [0.12] vs. 1.3 [0.23], P = .01). No significant
differences were found in the prevalence of moderate-to-severe white matter
hyperintensities across groups of sleep-disordered breathing (P = .40) or in the
mean apnea/hypopnea index across groups of persons with none-to-mild or moderate
to-severe white matter hyperintensities (P = .16). CONCLUSIONS: This pilot study
shows that moderate-to-severe sleep-disordered breathing correlates with cerebral
pulsatility, but such association might be independent of diffuse small vessel
disease.
PMID- 26420375
TI - IL-18-induced expression of high-affinity IL-2R on murine NK cells is essential
for NK-cell IFN-gamma production during murine Plasmodium yoelii infection.
AB - Early production of pro-inflammatory cytokines, including IFN-gamma, is essential
for control of blood-stage malaria infections. We have shown that IFN-gamma
production can be induced among human natural killer (NK) cells by coculture with
Plasmodium falciparum infected erythrocytes, but the importance of this response
is unclear. To further explore the role of NK cells during malaria infection, we
have characterized the NK-cell response of C57BL/6 mice during lethal (PyYM) or
nonlethal (Py17XNL) P. yoelii infection. Ex vivo flow cytometry revealed that NK
cells are activated within 24 h of Py17XNL blood-stage infection, expressing CD25
and producing IFN-gamma; this response was blunted and delayed during PyYM
infection. CD25 expression and IFN-gamma production were highly correlated,
suggesting a causal relationship between the two responses. Subsequent in vitro
experiments revealed that IL-18 signaling is essential for induction of CD25 and
synergizes with IL-12 to enhance CD25 expression on splenic NK cells. In
accordance with this, Py17XNL-infected erythrocytes induced NK-cell CD25
expression and IFN-gamma production in a manner that is completely IL-18- and
partially IL-12-dependent, and IFN-gamma production is enhanced by IL-2. These
data suggest that IL-2 signaling via CD25 amplifies IL-18- and IL-12-mediated NK
cell activation during malaria infection.
PMID- 26420376
TI - Visible-light-accelerated oxygen vacancy migration in strontium titanate.
AB - Strontium titanate is a model transition metal oxide that exhibits versatile
properties of special interest for both fundamental and applied researches. There
is evidence that most of the attractive properties of SrTiO3 are closely
associated with oxygen vacancies. Tuning the kinetics of oxygen vacancies is then
highly desired. Here we reported on a dramatic tuning of the electro-migration of
oxygen vacancies by visible light illumination. It is found that, through
depressing activation energy for vacancy diffusion, light illumination remarkably
accelerates oxygen vacancies even at room temperature. This effect provides a
feasible approach towards the modulation of the anionic processes. The principle
proved here can be extended to other perovskite oxides, finding a wide
application in oxide electronics.
PMID- 26420378
TI - Neuronal circuits: Looking after your own.
PMID- 26420379
TI - Highlights from SelectBio 2015: Academic Drug Discovery Conference, Cambridge,
UK, 19-20 May 2015.
AB - The SelectBio 2015: Academic Drug Discovery Conference was held in Cambridge, UK,
on 19-20 May 2015. Building on the success of academic drug discovery events in
the USA, this conference aimed to showcase the exciting new research emerging
from academic drug discovery and to help bridge the gap between basic research
and commercial application. At the event the authors heard from a number of
speakers on a broad array of topics, from partnering models for academia and
industry to novel drug discovery approaches across various therapeutic areas,
with a few talks, such as those by Susanne Muller-Knapp (Structure Genomics
Consortium, Oxford University, Oxford, UK) and Julian Blagg (Institute of Cancer
Research, UK), covering both remits, by highlighting a number of such
partnerships and then delving into some case studies. The conference concluded
with a heated debate on whether phenotypic discovery should be favored over
targeted discovery in academia and pharma, in a panel discussion chaired by
Roland Wolkowicz (San Diego State University, USA).
PMID- 26420380
TI - Recurrent duplications of 17q12 associated with variable phenotypes.
AB - The ability to identify the clinical nature of the recurrent duplication of
chromosome 17q12 has been limited by its rarity and the diverse range of
phenotypes associated with this genomic change. In order to further define the
clinical features of affected patients, detailed clinical information was
collected in the largest series to date (30 patients and 2 of their siblings)
through a multi-institutional collaborative effort. The majority of patients
presented with developmental delays varying from mild to severe. Though
dysmorphic features were commonly reported, patients do not have consistent and
recognizable features. Cardiac, ophthalmologic, growth, behavioral, and other
abnormalities were each present in a subset of patients. The newly associated
features potentially resulting from 17q12 duplication include height and weight
above the 95th percentile, cataracts, microphthalmia, coloboma, astigmatism,
tracheomalacia, cutaneous mosaicism, pectus excavatum, scoliosis, hypermobility,
hypospadias, diverticulum of Kommerell, pyloric stenosis, and
pseudohypoparathryoidism. The majority of duplications were inherited with some
carrier parents reporting learning disabilities or microcephaly. We identified
additional, potentially contributory copy number changes in a subset of patients,
including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data
further define and expand the clinical spectrum associated with duplications of
17q12 and provide support for the role of genomic modifiers contributing to
phenotypic variability.
PMID- 26420382
TI - Increasing incidence of type 1 diabetes among Korean children and adolescents:
analysis of data from a nationwide registry in Korea.
AB - BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in children and
adolescents has increased worldwide. However, the epidemiology of T1DM among
Korean youth has not been reported since 2001. We investigated the incidence of
T1DM in Korean children and adolescents from 2012 to 2014 and compared it with
data from 1995 to 2000. PATIENTS AND METHODS: Data were obtained from the
National Health Insurance Service (NHIS) registry, and age- and sex-specific
incidence rates were calculated per 100 000 population. RESULTS: In total, 706
patients (326 boys and 380 girls, aged <15 yr) with T1DM were registered in the
NHIS during 2012-2014. The incidence rate per 100 000 population was 3.19 (95%
confidence interval [CI] 2.96-3.43). We found incidence rates of 1.68, 3.16, and
4.46 in children 0-4, 5-9, and 10-14 yr, respectively. The T1DM incidence was
2.84 in boys and 3.56 in girls. A higher T1DM incidence was seen during 2012-2014
than from 1995-2000 (incidence rate ratio 2.33; p < 0.001). The incidence rate
ratios between 1995-2000 and 2012-2014 were 2.31, 2.20, and 2.27 in children 0-4,
5-9, and 10-14 yr, respectively. The annual increase in T1DM incidence was 5.6%
(95% CI 5.0-6.3%) between 1995 and 2014. CONCLUSIONS: We observed a significant
increase in the T1DM incidence. This increase was higher in boys than in girls,
and was highest in children aged 0-4 yr. Studies are needed to evaluate the long
term epidemiological trend of T1DM incidence.
PMID- 26420377
TI - Proliferation control in neural stem and progenitor cells.
AB - Neural circuit function can be drastically affected by variations in the number
of cells that are produced during development or by a reduction in adult cell
number owing to disease. For this reason, unique cell cycle and cell growth
control mechanisms operate in the developing and adult brain. In Drosophila
melanogaster and in mammalian neural stem and progenitor cells, these mechanisms
are intricately coordinated with the developmental age and the nutritional,
metabolic and hormonal state of the animal. Defects in neural stem cell
proliferation that result in the generation of incorrect cell numbers or defects
in neural stem cell differentiation can cause microcephaly or megalencephaly.
PMID- 26420383
TI - Design, synthesis and structure-activity relationship studies of novel
phenoxyacetamide-based free fatty acid receptor 1 agonists for the treatment of
type 2 diabetes.
AB - The free fatty acid receptor 1 (FFA1) has attracted extensive attention as a
novel antidiabetic target in the last decade. Several FFA1 agonists reported in
the literature have been suffered from relatively high molecular weight and
lipophilicity. We have previously reported the FFA1 agonist 1. Based on the
common amide structural characteristic of SAR1 and NIH screened compound, we here
describe the continued structure-activity exploration to decrease the molecular
weight and lipophilicity of the compound 1 series by converting various amide
linkers. All of these efforts lead to the discovery of the preferable lead
compound 18, a compound with considerable agonistic activity, high LE and LLE
values, lower lipophilicity than previously reported agonists, and appreciable
efficacy on glucose tolerance in both normal and type 2 diabetic mice.
PMID- 26420384
TI - Molecular modeling studies and synthesis of novel quinoxaline derivatives with
potential anticancer activity as inhibitors of c-Met kinase.
AB - In an effort to develop potent anti-cancer agents, we have synthesized some
substituted quinoxaline derivatives. Reaction of 6-bromo-3-methylquinoxalin-2(1H)
one 1 with aromatic aldehydes furnished the styryl derivatives 2a-e. Alkylation
of 1 with ethyl chloroacetate produced the N-alkyl derivatives 3. Hydrazinolysis
of the ester derivative 3 with hydrazine hydrate afforded the hydrazide
derivative 4. In addition, chlorination of 1 with phosphorus oxychloride afforded
the 2-chloro derivative 5 which was used as a key intermediate for the synthesis
of substituted quinoxaline derivatives 6-8, N-pyrazole derivative 9,
tetrazolo[1,5-a]quinoxaline derivative 10 and Schiff base derivatives 13, 15 via
reaction with several nucleophiles reagents. Docking methodologies were used to
predict their binding conformation to explain the differences of their tested
biological activities. All the tested compounds were screened in vitro for their
cytotoxic effect on three tumor cell lines. Some new quinoxaline derivatives were
studied as inhibitors of c-Met kinase, a receptor associated with high tumor
grade and poor prognosis in a number of human cancers. Compounds 2e, 4, 7a, 12a,
12b and 13 showed the highest binding affinity with CDOCKER energy score, while
showed the lowest IC50 values against three types of cancer cell lines. It is
worth to mention that, compounds 2e, 7a, 12b and 13 showed comparable inhibition
activity to the reference drug, while compounds 4 and 12a showed a more potent
inhibition activity than Doxorubicin.
PMID- 26420385
TI - CARE OF A PATIENT'S VASCULAR ACCESS FOR HAEMODIALYSIS: A NARRATIVE LITERATURE
REVIEW.
AB - BACKGROUND: Patients requiring haemodialysis have diverse clinical needs
impacting on the longevity of their vascular access and their quality of life. A
clinical practice scenario is presented that raises the potential of unsafe
cannulation of a patient's vascular access as a result of minimal patient
empowerment. Vascular access care is the responsibility of everyone, including
the patient and carer. AIM: The aim of this narrative literature review (1997
2014) is to explore the current understanding of what factors influence the care
of vascular access for haemodialysis. METHOD: A narrative literature review
allows the synthesis of the known literature pertinent to the research question
into a succinct model or unique order to enable new understandings to emerge. The
bio-ecological model was used to guide the thematic analysis of the literature.
RESULTS: The narrative literature review revealed five themes related to care of
vascular access: patient experience; relationships-empowerment and shared
decision making; environment of healthcare; time; and quality of life as the
outcome of care. CONCLUSION: The management of vascular access is complicated.
Current available literature predominantly concentrates on bio-medical aspects of
vascular access care. Contextualised vascular access care in the complex ecology
of the patient and carer's lives has the potential to enhance nursing practice
and patient outcomes.
PMID- 26420386
TI - Islamist insurgency and the war against polio: a cross-national analysis of the
political determinants of polio.
AB - BACKGROUND: There is widespread agreement that civil war obstructs efforts to
eradicate polio. It is suggested that Islamist insurgents have a particularly
negative effect on vaccination programmes, but this claim is controversial.
METHODS: We analyse cross-national data for the period 2003-14 using negative
binomial regressions to investigate the relationship between Islamist and non
Islamist insurgency and the global distribution of polio. The dependent variable
is the annual number of polio cases in a country according to the WHO. Insurgency
is operationalized as armed conflict between the state and an insurgent
organization resulting in >=25 battle deaths per year according to the Uppsala
Conflict Data Programme. Insurgencies are divided into Islamist and non-Islamist
insurgencies. We control for other possible explanatory variables. RESULTS:
Islamist insurgency did not have a significant positive relationship with polio
throughout the whole period. But in the past few years - since the assassination
of Osama bin Laden in 2011- Islamist insurgency has had a strong effect on where
polio cases occur. The evidence for a relationship between non-Islamist
insurgency and polio is less compelling and where there is a relationship it is
either spurious or driven by ecological fallacy. CONCLUSIONS: Only particular
forms of internal armed conflict - those prosecuted by Islamist insurgents -
explain the current global distribution of polio. The variation over time in the
relationship between Islamist insurgency and polio suggests that Islamist
insurgent's hostility to polio vaccinations programmes is not the result of their
theology, as the core tenets of Islam have not changed over the period of the
study. Rather, our analysis indicates that it is a plausibly a reaction to the
counterinsurgency strategies used against Islamist insurgents. The assassination
of Osama bin Laden and the use of drone strikes seemingly vindicated Islamist
insurgents' suspicions that immunization drives are a cover for espionage
activities.
PMID- 26420389
TI - Using self-assessments to enhance business continuity programmes.
AB - Self-assessments have limitations and are no substitute for independent audits of
a business continuity programme. Nevertheless, they can be an economical way to
identify gaps, enhance the programme and create awareness. Self- assessments can
also help prepare the programme and team members for an independent audit. In a
resource-constrained environment, self-assessments can provide an opportunity to
obtain measurable outputs about current state that can be tracked over time to
capture improvement and maturity or identify deficiencies. Self-assessments can
have a valuable place in any business continuity programme.
PMID- 26420390
TI - The synergy needed for business resilience.
AB - This paper discusses best practices on where to strategically connect risk
management, business continuity, disaster recovery, crisis management, crisis
communications, physical security, cyber security and emergency planning within
the organisation.
PMID- 26420387
TI - Calcium intake and risk of fracture: systematic review.
AB - OBJECTIVE: To examine the evidence underpinning recommendations to increase
calcium intake through dietary sources or calcium supplements to prevent
fractures. DESIGN: Systematic review of randomised controlled trials and
observational studies of calcium intake with fracture as an endpoint. Results
from trials were pooled with random effects meta-analyses. DATA SOURCES: Ovid
Medline, Embase, PubMed, and references from relevant systematic reviews. Initial
searches undertaken in July 2013 and updated in September 2014. ELIGIBILITY
CRITERIA FOR SELECTING STUDIES: Randomised controlled trials or cohort studies of
dietary calcium, milk or dairy intake, or calcium supplements (with or without
vitamin D) with fracture as an outcome and participants aged >50. RESULTS: There
were only two eligible randomised controlled trials of dietary sources of calcium
(n=262), but 50 reports from 44 cohort studies of relations between dietary
calcium (n=37), milk (n=14), or dairy intake (n=8) and fracture outcomes. For
dietary calcium, most studies reported no association between calcium intake and
fracture (14/22 for total, 17/21 for hip, 7/8 for vertebral, and 5/7 for forearm
fracture). For milk (25/28) and dairy intake (11/13), most studies also reported
no associations. In 26 randomised controlled trials, calcium supplements reduced
the risk of total fracture (20 studies, n=58,573; relative risk 0.89, 95%
confidence interval 0.81 to 0.96) and vertebral fracture (12 studies, n=48,967.
0.86, 0.74 to 1.00) but not hip (13 studies, n=56,648; 0.95, 0.76 to 1.18) or
forearm fracture (eight studies, n=51,775; 0.96, 0.85 to 1.09). Funnel plot
inspection and Egger's regression suggested bias toward calcium supplements in
the published data. In randomised controlled trials at lowest risk of bias (four
studies, n=44,505), there was no effect on risk of fracture at any site. Results
were similar for trials of calcium monotherapy and co-administered calcium and
vitamin D. Only one trial in frail elderly women in residential care with low
dietary calcium intake and vitamin D concentrations showed significant reductions
in risk of fracture. CONCLUSIONS: Dietary calcium intake is not associated with
risk of fracture, and there is no clinical trial evidence that increasing calcium
intake from dietary sources prevents fractures. Evidence that calcium supplements
prevent fractures is weak and inconsistent.
PMID- 26420388
TI - TRPM2 protects against tissue damage following oxidative stress and ischaemia
reperfusion.
AB - TRPM channels are a subgroup of the transient receptor potential (TRP) channel
superfamily whose members have important roles in cell proliferation and
survival. TRPM2, the second subfamily member to be cloned, is expressed in many
tissues including brain, heart, vasculature and haematopoietic cells. TRPM2 is
activated by oxidative stress and several other extracellular signals including
tumour necrosis factor alpha (TNF-alpha) and amyloid beta-peptide, which increase
production of ADP-ribose (ADPR). ADPR binds to the TRPM2 C-terminal NUDT9-H
domain, activating the channel. Early studies support the paradigm that TRPM2
activation induces cell death by sustained Ca(2+) influx or by enhancing cytokine
production, aggravating inflammation and tissue injury. However, more recent data
show that for a number of physiological processes, TRPM2 is protective. TRPM2
protects lungs from endotoxin-induced injury by reducing reactive oxygen species
(ROS) production by phagocytes. It protects hearts from oxidative damage after
ischaemia-reperfusion or hypoxia-reoxygenation by maintaining better
mitochondrial bioenergetics and by decreasing ROS. Sustained Ca(2+) entry through
TRPM2 is required to maintain cellular bioenergetics and protect against hypoxia
reoxygenation injury. TRPM2 also protects neuroblastoma from moderate oxidative
stress by decreasing ROS through increased levels of forkhead box transcription
factor 3a (FOXO3a) and a downstream effector, superoxide dismutase 2. TRPM2 is
important for tumour growth and cell survival through modulation of hypoxia
inducible transcription factor expression, mitochondrial function and mitophagy.
These findings in cardiac ischaemia and in neuroblastoma suggest that TRPM2 has a
basic role in sustaining mitochondrial function and in cell survival that applies
to a number of physiological systems and pathophysiological processes including
ischaemia-reperfusion injury.
PMID- 26420391
TI - Changing the paradigm of emergency response: The need for first-care providers.
AB - There is a major gap in the security of the critical infrastructure - civilian
medical response to atypical emergencies. Clear evidence demonstrates that,
despite ongoing improvements to the first-responder system, there exists an
inherent delay in the immediate medical care at the scene of an emergency. This
delay can only be reduced through a societal shift in reliance on police and fire
response and by extending the medical system into all communities. Additionally,
through analysis of military data, it is known that immediately addressing the
common injury patterns following a traumatic event will save lives. The
predictable nature of these injuries, coupled with an unavoidable delay in the
arrival of first responders, necessitates the need for immediate care on scene.
Initial care is often rendered by bystanders, typically armed only with basic
first-aid training based on medical emergencies and does not adequately address
the traumatic injury patterns seen in disasters. Implementing an approach similar
to the American Cardiac Arrest Act can improve outcomes to traumatic events. This
paper analyses the latest data on active shooter incidents and proposes that the
creation of a network of trauma-trained medic extenders would improve all
communities' resilience to catastrophic disaster.
PMID- 26420392
TI - Black sky: Exposing electricity as the Achilles' heel of resilience.
AB - The national power grid is the most critical and the most vulnerable life-support
infrastructure in modern society. Electricity serves as the essential element in
sustaining every other sector of critical infrastructure including water, fuel
and communications. Collective experience with responding to and recovering from
widespread, long-duration power outages - known as black sky events - is nearly
non-existent. Understanding these risks and weaknesses requires a collaborative
planning effort with the public and private sectors to identify and protect
critical nodes within the interdependent infrastructure to ensure that recovery
from a catastrophic event is possible. This also requires a 'whole community'
approach to planning and execution to facilitate a response on an unprecedented
level.
PMID- 26420393
TI - Initial response to a range of physical threats in an office environment.
AB - The paper proposes that there are a number of low-probability, but not
insignificant, physical threat scenarios relating to the office environment that
warrant an initial response capability (in addition to fire evacuation drill).
Explosive, contamination and intruder scenarios are included in the threats'
scope. The term 'initial response' essentially refers to first actions relating
to how and where to direct people to preserve life safety. Given the likelihood
that an organisation would not have any emergency services support in the early
stages of an incident, it follows that it is likely that the organisation would
be 'on its own' to assess, decide and execute the initial response. Aside from
any moral obligations, the paper proposes that there are potential legal
obligations to compel an organisation to be so prepared. An important
consideration explored is the feasibility of having an effective initial response
capability. The relative simplicity and low cost of implementation and
maintenance of a response is described. Lastly, the point is made that, aside
from fire evacuation (which is a drill), all the other threat scenarios discussed
require some decision making. It is not possible to be 100 per cent correct 100
per cent of the time. A decision support matrix is described with the objective
of increasing the percentage chance of making the most appropriate decision most
of the time. In particular, this is seen as an area for further discussion.
PMID- 26420394
TI - Business continuity, emergency planning and special needs: How to protect the
vulnerable.
AB - Emergencies and disasters affect all segments of the population. Some segments
are more at risk during the emergency response and recovery efforts owing to
vulnerabilities that increase the risk of harm. These vulnerabilities are due to
individuals' disabilities, which must be incorporated into emergency and business
continuity planning. Some disabilities are obvious, such as impaired vision,
hearing or mobility, while other are less evident, but equally disabling, such as
cognitive disorders, geographical or language isolation, and numerous age-related
factors. Taken together when creating emergency or business continuity plans, the
issues identified as disabilities can be grouped by functionality and termed as
special needs. This paper will detail the identification of special needs
populations, explain how these persons are vulnerable during the emergency or
disaster response and recovery process, and provide examples of how to partner
with individuals within identified special needs populations to improve the
planning process.
PMID- 26420395
TI - Effective information management and assurance for a modern organisation during a
crisis.
AB - During a crisis, organisations face a major unpredictable event with potentially
negative consequences. Effective information management and assurance can assist
the organisation in making sure that they have the correct information in a
secure format to make decisions to recover their operations. The main elements of
effective information management and assurance are confidentiality, integrity and
availability, combined with non-repudiation. Should an element of effective
information management or assurance be removed it can have a detrimental effect
on the other elements and render the information management and assurance
practices of the organisation ineffectual.
PMID- 26420396
TI - The hexagon hypothesis: Six disruptive scenarios.
AB - This paper aims to bring a simple but effective and comprehensive approach to the
development, delivery and monitoring of business continuity solutions. To ensure
that the arguments and principles apply across the board, the paper sticks to
basic underlying concepts rather than sophisticated interpretations. First, the
paper explores what exactly people are defending themselves against. Secondly,
the paper looks at how defences should be set up. Disruptive events tend to
unfold in phases, each of which invites a particular style of protection, ranging
from risk management through to business continuity to insurance cover. Their
impact upon any business operation will fall into one of six basic scenarios. The
hexagon hypothesis suggests that everyone should be prepared to deal with each of
these six disruptive scenarios and it provides them with a useful benchmark for
business continuity.
PMID- 26420397
TI - Hedging against terrorism: Are US businesses prepared?
AB - Private US companies face risks in connection with financial matters, but are not
necessarily prepared to cope with risks that can seriously disrupt or even halt
their operations, notably terrorist attacks and natural disasters. Enhancing the
resilience of businesses when dealing with terrorism is especially challenging,
as these groups or individuals can adapt tactics to exploit the vulnerabilities
of companies they wish to target. Business managers need to formulate flexible
preparedness plans that reduce risks from large-scale natural disasters as well
as terrorist attacks. In doing so, they can take advantage of post-9/11 US
government guidance for these endeavours as well as programmes that eliminate
risks to private insurance entities so they can issue policies that cover
terrorist strikes of high consequences. Just as business executives use hedging
strategies in the world of finance, they also need operational hedging strategies
as a means of exploiting as well as lowering the risks surrounding future
uncertainties. Resources devoted to planning and hedging are investments that can
increase the odds of businesses surviving and thriving, even if they experience
high-impact terrorist attacks, threats or large-scale natural disasters, making
suppliers, customers and stakeholders happy. The purpose of this paper is to give
executives the incentive to take steps to do just that.
PMID- 26420398
TI - Community resilience assessment and literature analysis.
AB - Earlier and current disaster-related research emphasised the
sociological/behavioural perspective. This led to a significant amount of
literature devoted to descriptive context of natural, man-made and technological
disasters and sequelae. This paper considers a next step involving a more
expanded approach in research methodology. The phases include: (1) the
development of a comprehensive database of ideas provided by authors of scholarly
and scientific papers; (2) the development of computer-supported algorithms to
prepare an array of scenarios representing relationships, gaps and
inconsistencies in existing knowledge; (3) a process for evaluating the scenarios
to determine a feasible and interesting next research strategy or programmatic
action that will provide enhanced description of the problems as well as possible
insights to their correction by interventions. The intent is to develop
interventions as an essential component for better prevention, mitigation,
rehabilitation, reconstruction and problem-solving affected by disaster events.
To illustrate this approach, community resilience, a relatively new and important
idea was studied. The phrase was used to describe relationships and omissions.
The ideas associated with this central idea were considered in the building of a
new instrument for evaluation of community vulnerability and readiness. This
methodology addresses the time constraints realised by practitioners and
investigators. The methods should eliminate tedious, clerical functions and focus
on the intellectual functions representing optimal use of human energy.
PMID- 26420399
TI - Using self-assessments to enhance business continuity programmes.
AB - Self-assessments have limitations and are no substitute for independent audits of
a business continuity programme. Nevertheless, they can be an economical way to
identify gaps, enhance the programme and create awareness. Self- assessments can
also help prepare the programme and team members for an independent audit. In a
resource-constrained environment, self-assessments can provide an opportunity to
obtain measurable outputs about current state that can be tracked over time to
capture improvement and maturity or identify deficiencies. Self-assessments can
have a valuable place in any business continuity programme.
PMID- 26420400
TI - Novel Coumarin Substituted Water Soluble Cyclophosphazenes as "Turn-Off" Type
Fluorescence Chemosensors for Detection of Fe(3+) ions in Aqueous Media.
AB - In the present work, 3-[2-(diethylamino)ethyl]-7-oxy-4-methylcoumarin substituted
cyclotriphosphazene (4) and cyclotetraphosphazene (5) derivatives were
synthesized by the reactions of hexachlorocyclotriphosphazene (1) or
octachlorocyclotetraphosphazene (2) with 3-[2-(diethylamino)ethyl]-7-hydroxy-4
methylcoumarin (3) for the first time. The quaternized cationic (6 and 7) and
zwitterionic (8 and 9) derivatives of these compounds (4 and 5) were obtained by
the reactions of dimethyl sulfate and 1,3-propanesultone, respectively. All newly
synthesized cyclophosphazene compounds (4-9) were fully characterized by
elemental analysis and general spectroscopic techniques such as FT-IR, (31)P-NMR,
(1)H-NMR and MALDI-TOF mass. All these coumarin substituted cyclophosphazene
compounds (4-9) were soluble in most of organic solvents and quaternized ionic
and zwitterionic compounds (6-9) also showed excellent solubility in water. The
fluorescence behaviors of novel cyclophosphazene compounds were investigated in
methanol and water solutions. The chemosensor properties of newly synthesized
water soluble quaternized ionic and zwitterionic cyclotriphosphazene and
cyclotetraphosphazene derivatives (6-9) were investigated in aqueous media. These
cyclophosphazene derivatives showed fluorescence chemosensor behavior with high
selectivity for Fe(3+) ions in aqueous solution.
PMID- 26420401
TI - Depressive episodes, symptoms, and trajectories in women recently diagnosed with
breast cancer.
AB - Depression carries serious psychosocial, physical, and economic consequences for
cancer survivors. Study goals were to characterize patterns and predictors of
depressive symptoms and major depressive episodes in recently diagnosed breast
cancer patients. Consecutively recruited women (N = 460) completed a validated
interview (CIDI) and questionnaire measure (CES-D) of depression within 4 months
after invasive breast cancer diagnosis and at six additional assessments across
12 months. Outcomes were major depressive episodes, continuous symptom scores,
and latent symptom trajectory classes. Across 12 months, 16.6 % of women met
criteria for a major depressive episode. Unemployment predicted depressive
episodes after other correlates were controlled. Distinct trajectory classes were
apparent: an estimated 38 % of women had chronically elevated symptoms (High
trajectory), 20 % recovered from elevated symptoms (Recovery), and 43 % had lower
symptoms (Low and Very Low trajectories). Although 96 % of episodes occurred in
the High or Recovery classes, 66 % of women in the High trajectory did not have
an episode. Women in the Low (vs High) trajectory were more likely to be older,
retired, more affluent, and have fewer comorbid diseases and briefer oncologic
treatment. Women in the Recovery trajectory (vs High) were more likely to be
married and more affluent and have fewer comorbid diseases. Assuming available
therapeutic resources, assessment of both depressive symptoms and episodes over
several months after diagnosis is important. Identification of patients at risk
for persistently high depressive symptoms (e.g., younger, longer treatment
course) opens targeted opportunities to prevent and promote rapid recovery from
depression.
PMID- 26420402
TI - Pneumocystis jiroveci pneumonia (PCP) in patients receiving neoadjuvant and
adjuvant anthracycline-based chemotherapy for breast cancer: incidence and risk
factors.
AB - Opportunistic infection with Pneumocystis jiroveci pneumonia (PCP) has not been
recognized as a significant complication of early-stage breast cancer treatment.
However, we have observed an increase in PCP incidence among patients receiving
chemotherapy for early-stage breast cancer. Herein we identify risk factors for
and calculate incidence of PCP in this population. We identified all cases of PCP
at Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH) from
1/1/2000 to 12/31/2013 in patients with stage I-III breast cancer treated with an
adriamycin/cyclophosphamide (AC)-containing regimen. Nineteen cases of PCP in non
metastatic breast cancer patients were identified. All patients with PCP were
diagnosed after receipt of either three or four cycles of AC chemotherapy on a
dose-dense schedule. Patients who developed PCP were treated with median 16.4 mg
prednisone equivalents/day as nausea prophylaxis for a median 64 days. The
overall incidence of PCP among 2057 patients treated with neoadjuvant or adjuvant
dose-dense AC for three or more cycles was 0.6 % (95 % confidence interval 0.3
1.0 %). No PCP was diagnosed in 1001 patients treated with non-dose-dense AC.
There was one death from PCP. Women receiving dose-dense AC chemotherapy for
early-stage breast cancer are at risk for PCP. Administering the same
chemotherapy and corticosteroid dose over an 8-week versus 12-week non-dose-dense
schedule appears to have created a novel infectious vulnerability. Replacing
dexamethasone with alternative anti-emetics may mitigate this risk.
PMID- 26420403
TI - Is a higher boost dose of radiation necessary after breast-conserving therapy for
patients with breast cancer with final close or positive margins?
AB - To determine rates of loco-regional recurrence (LRR), distant failure and overall
survival for patients with breast cancer treated with breast-conserving therapy
(BCT) with a close or positive surgical margin (C/PM) treated with standard dose
boost radiation compared with a higher boost of radiation. We retrospectively
studied 1476 patients with T1-T3 invasive breast cancer treated with BCT between
1992 and 2009. Median age was 57 years. Patients were divided into three groups:
Group I included 1197 patients (81 %) with negative margins who received a
standard boost (median 60 Gy) total dose to the lumpectomy cavity; Group II
included 116 patients (8 %) with C/PM who received a standard boost (median 60
Gy); and Group III included 163 patients (11 %) with C/PM who received a higher
boost (median 68 Gy). Biological subtypes (e.g., ER, PR, HER2/neu) were available
for 858 patients (58 %) and were also assessed for any relationship to LRR rate.
The Kaplan-Meier, Cox-regression, and log-rank tests were used to estimate rates
of LRR and the significance of risk factors. Median follow-up was 8.6 years. The
overall 5- and 10-year cumulative incidences of LRR were 2.1 % (95 % CI 0.8-2.1
%) and 4.5 % (95 % CI 3.4-6.0 %), respectively. The 5- and 10-year cumulative
incidences of LRR for Group I (negative margins + standard boost) were 1.9 and
4.4 %; for Group II (C/PM + standard boost) were 3.9 and 7.0 %; and for Group III
(C/PM + higher boost) were 2.9 and 3.8 %, respectively. No statistically
significant differences in LRR rates were found among the three groups (p = 0.4).
Similar results were obtained for distant failure (p = 0.3) and overall survival
(p = 0.4). On multivariate analysis, tumor grade (p = 0.03), systemic-therapy (p
= 0.005), node positivity (p = 0.05), young age (p = 0.001), and biological
subtype (p = 0.04) were statistically significantly associated with higher LRR.
Higher boost dose and margin positivity were not significant. Our data suggest
that the 10-year risk of local recurrence for patients with close or positive
margins receiving a standard boost was 7 % compared to 3.8 % for those receiving
a higher boost; however, this difference was not significant. A higher boost dose
did not significantly improve local control, nor did margins impact LRR risk in
our cohort of patients.
PMID- 26420405
TI - Endurance, resistance and resilience in the South African health care system:
case studies to demonstrate mechanisms of coping within a constrained system.
AB - BACKGROUND: South Africa is at present undertaking a series of reforms to
transform public health services to make them more effective and responsive to
patient and provider needs. A key focus of these reforms is primary care and its
overburdened, somewhat dysfunctional and hierarchical nature. This comparative
case study examines how patients and providers respond in this system and cope
with its systemic demands through mechanisms of endurance, resistance and
resilience, using coping and agency literatures as the theoretical lenses.
METHODS: As part of a larger research project carried out between 2009 and 2010,
this study conducted semi-structured interviews and observations at health
facilities in three South African provinces. This study explored patient
experiences of access to health care, in particular, ways of coping and how
health care providers cope with the health care system's realities. From this
interpretive base, four cases (two patients, two providers) were selected as they
best informed on endurance, resistance and resilience. Some commentary from other
respondents is added to underline the more ubiquitous nature of these coping
mechanisms. RESULTS: The cases of four individuals highlight the complexity of
different forms of endurance and passivity, emotion- and problem-based coping
with health care interactions in an overburdened, under-resourced and, in some
instances, poorly managed system. Patients' narratives show the micro-practices
they use to cope with their treatment, by not recognizing victimhood and
sometimes practising unhealthy behaviours. Providers indicate how they cope in
their work situations by using peer support and becoming knowledgeable in
providing good service. CONCLUSIONS: Resistance and resilience narratives show
the adaptive power of individuals in dealing with difficult illness,
circumstances or treatment settings. They permit individuals to do more than
endure (itself a coping mechanism) their circumstances, though resistance and
resilience may be limited. These are individual responses to systemic forces. To
transform health care, mutually supportive interactions are required among and
between both patients and providers but their nature, as micro-practices, may
show a way forward for system change.
PMID- 26420404
TI - Black breast cancer survivors experience greater upper extremity disability.
AB - Over one-third of breast cancer survivors experience upper extremity disability.
Black women present with factors associated with greater upper extremity
disability, including: increased body mass index (BMI), more advanced disease
stage at diagnosis, and varying treatment type compared with Whites. No prior
research has evaluated the relationship between race and upper extremity
disability using validated tools and controlling for these factors. Data were
drawn from a survey study among 610 women with stage I-III hormone receptor
positive breast cancer. The disabilities of the arm, shoulder and hand
(QuickDASH) is an 11-item self-administered questionnaire that has been validated
for breast cancer survivors to assess global upper extremity function over the
past 7 days. Linear regression and mediation analysis estimated the relationships
between race, BMI and QuickDASH score, adjusting for demographics and treatment
types. Black women (n = 98) had 7.3 points higher average QuickDASH scores than
White (n = 512) women (p < 0.001). After adjusting for BMI, age, education,
cancer treatment, months since diagnosis, and aromatase inhibitor status, Black
women had an average 4-point (95 % confidence interval 0.18-8.01) higher
QuickDASH score (p = 0.04) than White women. Mediation analysis suggested that
BMI attenuated the association between race and disability by 40 %. Even several
years post-treatment, Black breast cancer survivors had greater upper extremity
disability, which was partially mediated by higher BMIs. Close monitoring of high
BMI Black women may be an important step in reducing disparities in cancer
survivorship. More research is needed on the relationship between race, BMI, and
upper extremity disability.
PMID- 26420407
TI - [A Study on the Chinese Name of Smallpox].
AB - The Zhou hou fang (Handbook of Formulae) is the earliest known ancient medical
book carrying the title of smallpox, called "lu chuan" (captive sore). Since
then, various names had been applied to this disorder, including "sheng chuang"
(holy sore), "tian chuang" (celestial sore), "wan dou chuang" (pea sore), "fu dou
chuang" (bran sore), and "dou zhen" (pox-rash). This frequent changes of disease
titles in its history is a significant mark of the evolution of TCM recognition
on smallpox related to its treatment and prevention, and folk-social customs. It
was not until the Republican period that the title of "pox-rash" was substituted
by smallpox, a specific title for this viral infection. This is also the outcome
showing the important position of TCM treatment and prevention for smallpox
replaced by the preventive method of modern smallpox vaccination.
PMID- 26420408
TI - [Patients' medical activities as viewed from medical case records of South
Ridge].
AB - There are plenty of materials recorded in the medical case records of the South
Ridge. Through these records, it is possible to understand the patients' idea of
their confidence toward the doctors, changing of invited doctors, pharmacological
views, religious behaviors for inviting doctors and giving prognosis, payment to
the doctors and their activities of public benefits. All these can offer help to
the overall understanding of therapeutic history.
PMID- 26420406
TI - Risk factors associated with the occurrence of proximal humerus fractures in
patients with rheumatoid arthritis: a custom strategy for preventing proximal
humerus fractures.
AB - To our knowledge, no prior report focused on the risk factors for proximal
humerus fractures in patients with rheumatoid arthritis. The purpose of this
study was to evaluate the association between potential risk factors and the
occurrence of proximal humerus fractures in patients with rheumatoid arthritis. A
total of 11,907 patients with rheumatoid arthritis were enrolled in our
observational cohort rheumatoid arthritis study between 2000 and 2012. Self
reported proximal humerus fractures were verified using the patients' medical
records. Cox proportional hazard models were used to analyze the independent
contribution of risk factors to the occurrence of proximal humerus fractures.
During follow-up (mean 5.6 years), 92 proximal humerus fractures were verified in
91 patients. Multivariate Cox regression analyses estimated that the hazard
ratios of sustaining a proximal humerus fracture were 1.37 for every 10-year
increase in age [95 % confidence interval (CI) 1.10-1.70; P < 0.01], 1.95 for
increases in serum C-reactive protein levels (mg/100 mL; 95 % CI 1.15-3.34; P <
0.05), 2.13 for a history of fractures (95 % CI 1.34-3.40; P < 0.01), 1.07 for
the daily prednisolone dose (per mg; 95 % CI 1.01-1.13; P < 0.05), and 1.97 for
oral bisphosphonate use (95 % CI 1.20-3.23; P < 0.01). Better control of
rheumatoid arthritis with a smaller daily prednisolone dose in elderly patients
with a history of fractures may be important for preventing proximal humerus
fractures.
PMID- 26420410
TI - [Studies on the doctor-patient relationship in early Chinese missionary
hospitals].
AB - During the 19th century, missionary hospitals were set up by the missionaries in
China, establishing a new doctor-patient relationship with doctors at the
dominant position. In the early Chinese missionary hospitals, the doctor-patient
relationship was relatively good, which could be seen from Chinese people's
feelings of gratitude to the medical missionaries. The early missionary hospitals
were totally controlled by the western Christians during the 1820-1860. Such good
doctor-patient relationship was the results of common action of multiple factors,
including Christianity, free medical charges, management idea based on humanism,
the idea of the hospitals to avoid medical risks, family concept in traditional
Chinese culture and so on.
PMID- 26420409
TI - [Contention on the theory of processing techniques of Chinese materia medica in
the Ming-Qing period].
AB - On the basis of the golden stage of development of processing techniques of
medicinals in the Song dynasty, the theory and techniques of processing in the
Ming-Qing dynasties developed and accomplished further. The knowledge of some
physicians on the processing of common medicinal, such as Radix rehmannia and
Radixophiopogonis, was questioned, with new idea of processing methods put
forward and argued against those insisting traditional ones, marking the progress
of the art of processing. By reviewing the contention of technical theory of
medicinal processing in the Ming-Qing period, useful references can be provided
for the inheritance and development of the traditional art of processing
medicinals.
PMID- 26420411
TI - [An introduction to the transmission of modern western medicine in southwestern
borderland].
AB - Yunnan is located in the southwestern border of China, neighboring South Asia and
Southeast Asia. Since the end ofthe 19th century, the western medicine was
introduced into Yunnan Province along with the arrival of missionaries, exerting
great influence on local medicine in Yunnan, even in inland China, and has become
an integral part of Chinese modern medical history. Initially, the missionaries
who knew only a little medical knowledge and treated the patients effectively
during their missionary work with the western medicines they carried, so as to
develop the believers. At the beginning of the 20th century, Catholic Church and
Christian Church began to establish Church Hospitals in Yunnan, including the
"Dafashi Hospital (French Consulate Hospital)" set up in 1901, and "Fudian
Hospital (French Government Hospital)" established in 1902, and many Hospitals
set up in Yunnan Province. The Church Hospitals also established medical schools
and nurse schools all over Yunnan, which promoted modern medical education in
Yunnan, and had profound influence on modern education of western medicine in
this Provence.
PMID- 26420412
TI - [On the formulation of TCM foreign exchange policy after the reform and opening
up].
AB - The foreign exchange activities of traditional Chinese medicine are conducted
under the guidance of the policy of the CPC and Chinese government. After the
carrying out of the reform and opening-up policy, foreign exchange policy of TCM
has experienced the process of growing up from nothing, from less to more, and
from coarse to fine, which is closely related to our country's foreign policy,
the cause of Chinese medicine development, and urgent need of international
communication. In the three decades after the reform and opening-up policy, the
formulation of foreign exchange policy of TCM can be divided into three stages:
viz., inclusion in the framework of national foreign policy (1978-1985),
embodiment in the policy of developing TCM cause (1986-1996), and appearance in
the special policy of foreign exchange of Chinese medicine (since 1997). From the
development process of these policies, the development of each policy gradually
complies with the process of the development of the times, with its contents
basically in line with the requirements of the times. The implementation of some
policies promotes the foreign exchanges and cooperation of Chinese medicine.
PMID- 26420413
TI - [Preliminary exploration on educational reform of general western medical history
in medical colleges and universities under new situations and circumstances].
AB - With the appearance of the "biological-psychological-social" medical model, the
purpose, value and significance of medicine are reviewed and reconsidered by the
people, and the history of medicine becomes one of the core subjects in the
medical humanist education, along with change of the teaching of general western
medical history. Medical history is no longer the accumulation of the
achievements of human knowledge and medical experience, the intellectual history
of theorytransformation, and the history of reformation of medical technologies,
but a concrete and colorful living situation, displayed by the scientists,
physicians and normal peoplecommunity during the process of their consistent
recognition and transformation on medicine. Therefore, the teaching of
generalwestern medical history should adjust the compilation of teaching
materials, update the educational concept, change the contents, methods of
teaching and examination in order to lay stress on the cultural viewpoint and the
function of humanity and quality of education.
PMID- 26420414
TI - [Textual research on circulation of the Ming edition of Li Heng's Xiu zhen fang
(Pocket Formulary)].
AB - Xiu zhen fang (Pocket Formulary) is a recipe book of the Ming Dynasty, inspired
and managed by Zhu Su, compiled by Li Heng of liangyisuo (good physician house)
in Zhou wangfu (Zhou's royal palace). The book was compiled and published twice
during the reigns of the Hongwu and Yongle Emperors of the Ming Dynasty. Because
of its high practicability, there were some editions in circulation, and the book
was published several times only in the Ming Dynasty. At present, the earliest
extanteditionwas the little character version of Yongle, and the version in the
4(th) year of Zhengde Emperor of the Ming Dynasty was a reprinting edition based
on the Yongle edition, sharingthe same edition system. Most of the editions
appeared after the reign of Zhengtong Emperor of the Ming Dynasty, titled by "kui
ben (head version)" and "da quan (complete edition)" were the editionspublished
in the local bookshops, which had rather distinct differences from the Yongle
edition system not only in the its format but also in its contents.
PMID- 26420415
TI - [Investigation on the number of ancient medical books collected in Haiyuan
Private Library].
AB - Yang's Haiyuan Private Library in Liaocheng City, Shandong Province, is the only
extant one among the four famous private libraries of the Qing dynasty in
Northern China. Its collection is ample and graceful and especially rich in rare
and secret versions, amounting to over 2 000 kinds, 200- thousand volumes. By
sorting out 5 kinds of such collections from the Yang's family catalogue of
Liaocheng in Shandong, plus 3 kinds of supplemented catalogue by Wang Shaozeng,
the Catalogue of Haiyuan Private Library Collected in Shandong Provincial
Library, and catalogues of modern scholars, it can be basically identified that
the number of medical collections of Yang's Haiyuan Private Library is 87 kinds.
Supposing all kinds contain 112 works, then Haiyuan Private Library totally has
1296 volumes according to the catalogues.
PMID- 26420416
TI - [Establishment and development of National Institutes of Health of the United
States].
AB - National Institutes of Health traces its root to a one-room laboratory created in
1887. Now it has become a federal agency including 27 institutes and centers,
also one of the world biggest centers of biomedical research.Throughout the
history of NIH, much experience is worth learning, for example: allocating
persistent and sufficient funds, basing on basic research and adjusting its focus
duly, expanding the scope of subsidizing and stressing talent cultivation.
PMID- 26420417
TI - Relation of serum 25-hydroxyvitamin D status with skeletal muscle mass by sex and
age group among Korean adults.
AB - The objective of this study was to examine whether high serum 25-hydroxyvitamin D
(25(OH)D) concentration was associated with high skeletal muscle mass, taking
into account the effects of sex and age among the participants of the Korea
National Health and Nutrition Examination Survey (KNHANES) aged 40 years or
older. This was a cross-sectional study using data from the 2009 to 2010 KNHANES;
a total of 8406 subjects (3671 men and 4735 women) were included. The
appendicular skeletal muscle mass index (ASMMI, kg/m2) was estimated to measure
the skeletal muscle mass. Hypovitaminosis was classified when the level of serum
25(OH)D was <20 ng/ml. The general linear model adjusted for confounding factors
was used to determine differences in means of ASMMI by 25(OH)D status. The mean
values of ASMMI were higher for men when compared with women. Women had a greater
proportion of hypovitaminosis (71.1%) compared with men (53.2%). After adjusting
for multiple factors, men were seen to have significant differences in ASMMI
based on 25(OH)D status regardless of age, showing a lower mean value of ASSMI in
those with hypovitaminosis. However, there was no difference in ASMMI by 25(OH)D
status among women in both younger and older age groups. In conclusion, we found
that there might be a positive relationship between 25(OH)D and skeletal muscle
mass in men, indicating that interventions to improve 25(OH)D levels that are
aimed at increasing muscle mass could be beneficial for men with more rapid
decreased rate of skeletal muscle mass.
PMID- 26420418
TI - Relief of obstructive jaundice from pancreatic cancer: the end of the plastic
stent era?
PMID- 26420419
TI - TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and
in vitro.
AB - OBJECTIVE: Cholestatic liver diseases in humans as well as bile acid (BA)-feeding
and common bile duct ligation (CBDL) in rodents trigger hyperplasia of
cholangiocytes within the portal fields. Furthermore, elevation of BA levels
enhances proliferation and invasiveness of cholangiocarcinoma (CCA) cells in
animal models, thus promoting tumour progression. TGR5 is a G-protein coupled BA
receptor, which is highly expressed in cholangiocytes and postulated to mediate
the proliferative effects of BA. DESIGN: BA-dependent cholangiocyte proliferation
was examined in TGR5-knockout and wild type mice following cholic acid (CA)
feeding and CBDL. TGR5-dependent proliferation and protection from apoptosis was
studied in isolated cholangiocytes and CCA cell lines following stimulation with
TGR5 ligands and kinase inhibitors. TGR5 expression was analysed in human CCA
tissue. RESULTS: Cholangiocyte proliferation was significantly reduced in TGR5
knockout mice in response to CA-feeding and CBDL. Taurolithocholic acid and TGR5
selective agonists induced cholangiocyte proliferation through elevation of
reactive oxygen species and cSrc mediated epidermal growth factor receptor
transactivation and subsequent Erk1/2 phosphorylation only in wild type but not
in TGR5-knockout-derived cells. In human CCA tissue TGR5 was overexpressed and
the pathway of TGR5-dependent proliferation via epidermal growth factor receptor
and extracellular signal-regulated kinase (ERK)1/2 activation also translated to
CCA cell lines. Furthermore, apoptosis was inhibited by TGR5-dependent CD95
receptor serine phosphorylation. CONCLUSIONS: TGR5 is an important mediator of BA
induced cholangiocyte proliferation in vivo and in vitro. Furthermore, TGR5
protects cholangiocytes from death receptor-mediated apoptosis. These mechanisms
may protect cholangiocytes from BA toxicity under cholestatic conditions,
however, they may trigger proliferation and apoptosis resistance in malignantly
transformed cholangiocytes, thus promoting CCA progression.
PMID- 26420420
TI - Endoplasmic reticulum protein 29 (ERp29) confers radioresistance through the DNA
repair gene, O(6)-methylguanine DNA-methyltransferase, in breast cancer cells.
AB - Resistance of cancer cells to radiotherapy is a major clinical problem in cancer
treatment. Therefore, understanding the molecular basis of cellular resistance to
radiotherapy and identification of novel targets are essential for improving
treatment efficacy for cancer patients. Our previous studies have demonstrated a
significant role of ERp29 in breast cancer cell survival against doxorubicin
induced genotoxic stress. We here reported that ERp29 expression in the triple
negative MDA-MB-231 breast cancer cells significantly increased cell survival
against ionizing radiation. Methylation PCR array analysis identified that ERp29
expression increased promoter hypomethylation of the DNA repair gene, O(6)
methylguanine DNA-methyltransferase (MGMT), by downregulating DNA
methyltransferase 1. Knockdown of MGMT in the ERp29-transfected cancer cells
increased radiosensitivity, leading to a decreased post-irradiation survival. In
addition, radiation treatment in the MGMT-knockdown cells elevated
phosphorylation of gamma-H2AX and cleavage of caspase 3, indicating that
depletion of MGMT facilitates DNA double strands breaks and increases cell
apoptosis. Hence, our studies prove a novel function of ERp29?MGMT in cancer cell
survival against radiation. Targeting ERp29?MGMT axis may be useful for providing
better treatment efficacy in combination with radiotherapy in breast cancer.
PMID- 26420421
TI - Opposing Effects of NGF and proNGF on HIV Induced Macrophage Activation.
AB - Macrophage and microglial activation by HIV in the central nervous system (CNS)
triggers the secretion of soluble factors which damage neurons. Therapeutic
approaches designed to restore cognitive function by suppressing this
inflammatory activity have not yet been successful. Recent studies have indicated
that the phenotype of macrophages is differentially controlled by the mature and
pro form of nerve growth factor. These cells therefore may be highly responsive
to the imbalance in pro versus mature neurotrophins often associated with
neurodegenerative diseases. In this study we evaluated the interactions between
neurotrophins and HIV induced macrophage activation. HIV stimulation of
macrophages induced a neurotoxic phenotype characterized by the expression of
podosomes, suppression of calcium spiking and increased neurotoxin production.
The secretome of the activated macrophages revealed a bias toward anti-angiogenic
like activity and increased secretion of MMP-9. Co-stimulation with NGF and HIV
suppressed neurotoxin secretion, increased calcium spiking, suppressed podosome
expression and reversed 86% of the proteins secreted in response to HIV,
including MMP-9 and many growth factors. In contrast, co-stimulation of
macrophages with proNGF not only failed to reverse the effects of HIV but
increased the neurotoxic phenotype. These differential effects of proNGF and NGF
on HIV activation provide a potential novel therapeutic avenue for controlling
macrophage activation in response to HIV.
PMID- 26420423
TI - Tele-health-care in the elderly living in nursing home: the first Sicilian
multimodal approach.
AB - BACKGROUND: The continued aging of the population is affecting the health of the
industrialized countries, with an increasing burden for the healthcare system.
Thus, during the last decade, we assisted to relevant progress in the medical
treatment and rehabilitation techniques and devices, including the development of
telemedicine for geriatric care. AIM: To demonstrate the effectiveness of a novel
tele-health-care model allowing a better management of elderly living in nursing
homes. METHODS: Fifty-nine elderly patients (19 males and 40 females; mean age
79.1 (+/-9.2), were randomly divided into two groups: the experimental group that
performed a proper telemonitoring with a multimodal approach (including
monitoring of the vital signs and neurological/psychological counseling), and the
control group, which underwent standard in-home nursing care. Neurobehavioral
symptoms and quality of life were assessed in both the groups at baseline, and
after the telecare protocol's end. RESULTS: The experimental group had a
statistically significant reduction in Geriatric Depression Scale (p < 0.01) and
Brief Psychiatric Rating Scale (p < 0.05) scores, and an improvement in their
quality of life. Moreover, mean blood pressure and heart rate were lower in the
experimental than in the control group (p < 0.05), and admission to health care
services was higher in the control than in the experimental group (p < 0.05).
CONCLUSIONS: Telemedicine can be considered as an important tool in improving
health and quality of life in the elderly living in nursing homes, and
potentially reducing healthcare service access, hospitalization, and costs.
PMID- 26420422
TI - The DNA structure and sequence preferences of WRN underlie its function in
telomeric recombination events.
AB - Telomeric abnormalities caused by loss of function of the RecQ helicase WRN are
linked to the multiple premature ageing phenotypes that characterize Werner
syndrome. Here we examine WRN's role in telomeric maintenance, by comparing its
action on a variety of DNA structures without or with telomeric sequences. Our
results show that WRN clearly prefers to act on strand invasion intermediates in
a manner that favours strand invasion and exchange. Moreover, WRN unwinding of
these recombination structures is further enhanced when the invading strand
contains at least three G-rich single-stranded telomeric repeats. These
selectivities are most pronounced at NaCl concentrations within the reported
intranuclear monovalent cation concentration range, and are partly conferred by
WRN's C-terminal region. Importantly, WRN's specificity for the G-rich telomeric
sequence within this precise structural context is particularly relevant to
telomere metabolism and strongly suggests a physiological role in telomeric
recombination processes, including T-loop dynamics.
PMID- 26420424
TI - Bullous pemphigoid and neurodegenerative diseases: a study in a setting of a
Central European university dermatology department.
AB - Bullous pemphigoid (BP) is an autoimmune blistering dermatosis of the elderly
mediated by IgG and IgE antibodies to skin hemidesmosomal proteins, BP180 and/or
BP230, that occur physiologically also in neuronal tissue. It was reported that
BP is associated with neurodegenerative diseases (ND). We performed a
retrospective study in a setting of a Central European university dermatology
department on prevalence of ND in 94 BP patients. 26 out of 94 BP patients had at
least one ND. ND included: Parkinson's disease, dementia, stroke, hear loss,
tinnitus, blindness, vertigo, neurosyphilis, systemic sclerosis, and epilepsy.
Since population aging is conceivably responsible for the rising number of BP
cases as a result of immunosenescence-related phenomena, the plausible BP
specific immunopathogenetic relationship between BP and ND deserves to be further
experimentally explored.
PMID- 26420425
TI - Assessment of the diagnostic efficacy of enolase as an indication of active
infection of Schistosoma japonicum.
AB - Schistosomiasis is a common zoonoses affecting humans. The atypical clinical
symptoms, low morbidity, and low degree of infection impede diagnosis and
assessment of epidemics. Detecting circulating antigens from adult worms in
patients' body fluids should be diagnostically superior to examining eggs in
feces. Herein, the excretory-secretory proteins of adult worms were analyzed by
using 2-D protein electrophoresis and mass spectrometry. The Schistosoma
japonicum enolase (Sj enolase) was identified as the most abundant excretory
secretory antigen. Purified recombinant Sj enolase was prepared, and specific
monoclonal and polyclonal antibodies were raised against it. A sandwich enzyme
linked immunoassay (sandwich ELISA) was established that used the monoclonal
antibody as a capture antibody and the polyclonal antibody as a detection
antibody. The linear detection range was 0.7-1000 ng/ml (minimum 700 pg/ml). Sj
enolase could be detected in the sera of infected rabbits and disappeared rapidly
postpraziquantel treatment. The sensitivity and specificity of this sandwich
ELISA to detect field serum samples of schistosomiasis were 84.61 and 95.83 %,
respectively. The cross-reaction rates for clonorchiasis and paragonimiasis were
3.33 and 5 %, respectively. This ELISA assay was used to test 45 matching sera of
schistosomiasis patients before treatment and at 3, 6, 9, and 12 months
posttreatment. Among the sera, 88.89 % were positive before treatment. At 3, 6,
9, and 12 months postpraziquantel treatment, 93.33, 97.78, 100, and 100 % tested
negative, respectively. Therefore, Sj enolase can be used to indicate active
Schistosoma infection, and detecting serum Sj enolase is important for diagnosis
and evaluating treatment effect.
PMID- 26420426
TI - The reciprocal effect of pain catastrophizing and satisfaction with participation
in the multidisciplinary treatment of patients with chronic back pain.
AB - BACKGROUND: The aim of the study was to examine the reciprocity between pain
catastrophizing, social participation and quality of life outcomes (pain
intensity, pain disability, negative affectivity) in patients with low back pain
in a multidisciplinary pain treatment. METHODS: Patients undergoing inpatient
rehabilitation were surveyed at the beginning and two weeks after the end of
rehabilitation. N = 262 low back pain patients participated (mean age: 52.2, 62.1
% female). A two-wave cross-lagged design and structural equation modeling were
used to analyze data. RESULTS: We found evidence of reciprocal relations with
regard to several outcomes. For example, pain catastrophizing at the beginning of
treatment is associated with negative affectivity after rehabilitation, and the
post-treatment value of pain catastrophizing is associated with pain disability
and satisfaction with participation at the start of treatment. Pain disability
and pain catastrophizing are predictors of lower treatment outcome while pain
intensity and negative affectivity are not risk factors. Participation stands in
a reciprocal relationship with some of the pain treatment outcomes. The
surprising result, namely, that those patients more satisfied with social
participation experience less improvement regarding catastrophizing, can be
explained by ceiling effects and the Communal Coping Model. CONCLUSIONS: This
study provides evidence of the importance of taking reciprocal relations among
pain catastrophizing, social participation and other pain outcomes into account.
Providers of multidisciplinary pain treatment need to play attention to patients
at risk with high disability and catastrophizing thoughts. Pain treatment would
benefit from closer integration of psychosocial measures to foster social
participation.
PMID- 26420427
TI - Analyses of acute kidney injury biomarkers by ultra-high performance liquid
chromatography with mass spectrometry.
AB - The newly developed acute kidney injury biomarkers are very important for the
early and timely detection of kidney diseases. This review contains details of
the analyses of several acute kidney injury biomarkers using ultra-high
performance liquid chromatography-mass spectrometry in urine and plasma samples.
In this review we attempt to discuss some aspects of the types of the biomarkers,
patents, sample preparation, and the analyses. Besides, efforts were also made to
discuss the possible uses of superficially porous (core-shell) columns in
traditional and inexpensive high-performance liquid chromatography instruments.
Additionally, the challenges and the future prospects are also highlighted. The
present review will be useful for the academicians, scientists, and clinicians
for the early detection of acute kidney injury biomarkers.
PMID- 26420428
TI - Clinical application of amplicon-based next-generation sequencing to therapeutic
decision making in lung cancer.
AB - BACKGROUND: The clinical implementation of genomic profiling for lung cancer with
high-throughput, multiplex tests is warranted to allow prioritization of
appropriate therapies for individual patients. We have now applied such testing
to detect actionable mutations that may inform treatment recommendations in lung
cancer. PATIENTS AND METHODS: We prospectively applied amplicon sequencing panels
that cover both mutational hotspots in 22 genes related to lung and colon
tumorigenesis as well as 72 major variants of ALK, RET, ROS1, and NTRK1 fusion
transcripts. We then determined the proportion of patients who received genotype
directed therapy and their overall survival (OS). RESULTS: Tumor specimens from
110 patients with lung cancer recruited between July 2013 and March 2015 were
analyzed. The most common genetic alterations were TP53 mutations in 42 patients,
followed by EGFR mutations in 25, STK11 mutations in 12, and KRAS mutations in
10. Potentially actionable mutations were identified in 44 patients including 50%
of those with adenocarcinoma and 14% of those with squamous cell carcinoma. The
OS of patients with advanced or recurrent cancer who had an actionable mutation
and received targeted therapy (median OS not achieved) was significantly longer
than that of those with no mutation (18.1 months, P = 0.041) or of those with a
mutation not so treated (6.1 months, P = 0.0027). CONCLUSIONS: Multiplex genomic
testing was performed on formalin-fixed, paraffin-embedded tumor specimens with a
success rate of >=95%. Such testing can assist physicians in matching patients
with approved or experimental targeted treatments. CLINICAL TRIAL REGISTRATION:
The University Medical Hospital Information Network (UMIN) Clinical Trials
Registry under the identifier UMIN000014782.
PMID- 26420429
TI - Glyma11g13220, a homolog of the vernalization pathway gene VERNALIZATION 1 from
soybean [Glycine max (L.) Merr.], promotes flowering in Arabidopsis thaliana.
AB - BACKGROUND: The precise timing of flowering is fundamental to successful
reproduction, and has dramatic significance for crop yields. Although prolonged
low temperatures are not required for flowering induction in soybean,
vernalization pathway genes have been retained during the evolution of this
species. Little information is currently available in regarding these genes in
soybean. RESULTS: We were able to detect the expression of Glyma11g13220 in
different organs at all monitored developmental stages in soybean. Glyma11g13220
expression was higher in leaves and pods than in shoot apexes and stems. In
addition, Glyma11g13220 was responsive to photoperiod and low temperature in
soybean. Furthermore, Glyma11g13220 was found to be a nuclear-localized protein.
Over-expression of Glyma11g13220 in an Arabidopsis Columbia-0 (Col-0) background
resulted in early flowering. Quantitative real-time PCR analysis revealed that
transcript levels of flower repressor FLOWERING LOCUS C (FLC), and FD decreased
significantly in transgenic Arabidopsis compared with wild-type Col-0, while the
expression of VERNALIZATION INSENSITIVE 3 (VIN3) and FLOWERING LOCUS T (FT)
noticeably increased. CONCLUSIONS: Our results suggest that Glyma11g13220, a
homolog of Arabidopsis VRN1, is a functional protein. Glyma11g13220, which is
responsive to photoperiod and low temperature in soybean, may participate in the
vernalization pathway in Arabidopsis and help regulate flowering time.
Arabidopsis VRN1 and Glyma11g13220 exhibit conserved as well as diverged
functions.
PMID- 26420433
TI - Mycobacterium gordonae-induced humidifier lung.
AB - BACKGROUND: Nontuberculous mycobacteria are well known to be a cause of hot tub
lung, however, to our knowledge, there exists no case report of humidifier lung
induced by mycobacteria. CASE PRESENTATION: A case of a nonimmunocompromised
female patient with Mycobacterium gordonae-induced humidifier lung is described.
She spontaneously recovered after discontinuing ultrasonic humidifier use. When
subjected to a provocation test, she demonstrated acute respiratory distress with
signs and symptoms, consistent with hypersensitivity pneumonitis. Before and
after the provocation test, water in the humidifier reservoir revealed only
Mycobacterium gordonae by the microbiologic analyses. CONCLUSION: To our
knowledge, this is the first report of humidifier lung induced by nontuberculous
mycobacteria. Although nontuberculous mycobacteria are well-known to be agents of
hot tub lung or metal working fluid lung, physicians should also consider the
pathogen as a cause of hypersensitivity lung reaction associated with humidifier
use.
PMID- 26420434
TI - A lncRNA to repair DNA.
AB - Long non-coding RNAs (lncRNAs) have emerged as regulators of various biological
processes, but to which extent lncRNAs play a role in genome integrity
maintenance is not well understood. In this issue of EMBO Reports, Sharma et al
[1] identify the DNA damage-induced lncRNA DDSR1 as an integral player of the DNA
damage response (DDR). DDSR1 has both an early role by modulating repair pathway
choices, and a later function when it regulates gene expression. Sharma et al [1]
thus uncover a dual role for a hitherto uncharacterized lncRNA during the
cellular response to DNA damage.
PMID- 26420435
TI - Possibility of monitoring granulation by analyzing the amount of
hydroxypropylcellulose, a binder on the surface of granules, using ToF-SIMS.
AB - The purpose of this study was to clarify the mechanism responsible for high-shear
wet granulation using time-of-flight secondary ion mass spectrometry (ToF-SIMS),
which can be used for surface chemical mapping. A total of 15 kinds of granules,
including hydroxypropylcellulose (HPC) as a binder, were obtained in a model
formulation using different granulation conditions, such as the amount of sprayed
water and the granulation time. Surface chemical mapping of these granules was
then performed using a ToF-SIMS analysis, which distinguishes each component by
detecting the specific mass-to-charge ratio (m/z). As a result, we found that HPC
got to appear on the surface of granule with proceeding wet granulation. By
considering this result, we concluded that the distributions of HPC might be
closely related to the progress of granule consolidation and growth in wet
granulation. Therefore, the progress of granulation can likely be understood by
measuring the content of HPC on the granule surface.
PMID- 26420436
TI - A descriptive review of cardiac tumours in dogs and cats.
AB - Cardiac tumours are uncommon in the canine and feline population and often an
incidental finding. Common types include haemangiosarcoma (HSA), aortic body
tumours (chemodectoma and paraganglioma) and lymphoma. These neoplasms can cause
mild to severe, life-threatening clinical signs that are independent of the
histological type and may be related to altered cardiovascular function or local
haemorrhage/effusion into the pericardial space. Cardiac tumours may require
symptomatic treatment aimed at controlling tumour bleeding and potential
arrhythmias, and other signs caused by the mass effect. Additional treatment
options include surgery, chemotherapy and radiotherapy. For all medical
therapies, complete remission is unlikely and medical management, beyond
adjunctive chemotherapy in HSA, requires further investigation but combination
chemotherapy is recommended for lymphoma. The aim of this report is to summarize
and critically appraise the current literature in a descriptive review. However,
interpretation is limited by the lack of definitive diagnosis and retrospective
nature of most studies.
PMID- 26420437
TI - Estimation of Recent and Ancient Inbreeding in a Small Endogamous Tunisian
Community Through Genomic Runs of Homozygosity.
AB - Runs of homozygosity (ROHs) are extended genomic regions of homozygous genotypes
that record populations' mating patterns in the past. We performed microarray
genotyping on 15 individuals from a small isolated Tunisian community. We
estimated the individual and population genome-wide level of homozygosity from
data on ROH above 0.5 Mb in length. We found a high average number of ROH per
individual (48.2). The smallest ROH category (0.5-1.49 Mb) represents 0.93% of
the whole genome, while medium-size (1.5-4.99 Mb) and long-size ROH (>=5 Mb)
cover 1.18% and 0.95%, respectively. We found that genealogical individual
inbreeding coefficients (Fped ) based on three- to four-generation pedigrees are
not reliable indicators of the current proportion of genome-wide homozygosity
inferred from ROH (FROH ) either for 0.5 or 1.5 Mb ROH length thresholds, while
identity-by-descent sharing is a function of shared coancestry. This study
emphasizes the effect of reproductive isolation and a prolonged practice of
consanguinity that limits the genetic heterogeneity. It also provides evidence of
both recent and ancient parental relatedness contribution to the current level of
genome-wide homozygosity in the studied population. These findings may be useful
for evaluation of long-term effects of inbreeding on human health and for future
applications of ROHs in identifying recessive susceptibility genes.
PMID- 26420438
TI - Erratum to: A new transcriptional variant and small azurophilic granules in an
acute promyelocytic leukemia case with NPM1/RARA fusion gene.
PMID- 26420439
TI - Mild to moderate increase of serum calcitonin levels only in presence of large
medullary thyroid cancer deposits.
AB - Many open questions remain to be elucidated about the diagnosis, treatment and
prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the
outcome of MTC patients after surgery. Great importance is usually given to serum
calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that
the higher are the levels of these tumor markers and their kinetics (double time
and velocity of markers levels) the worst is the prognosis. However, this is not
the rule, as there are huge MTC metastatic deposits characterized by low serum Ct
and CEA levels, and this condition is not closely related to the outcome of the
disease during post-surgical follow-up. A series is reported here of patients who
have these characteristics, as well as a description of their prognosis and
clinical outcome.
PMID- 26420440
TI - Long latency between GAD-antibody detection and development of limbic
encephalitis--a case report.
AB - BACKGROUND: In the pathogenesis of limbic encephalitis other promoting factors
besides the pure existence of autoantibodies are increasingly discussed to play a
significant role. This is to our knowledge the first described patient in whom
the presence of autoantibodies precedes the manifestation of limbic encephalitis
for many years. CASE PRESENTATION: At the age of 38 years, in the serum of a
patient with polyendocrine autoimmunity high titers of cytoplasmic islet cell
antibodies and of anti-glutamate decarboxylase (GAD) 65 antibodies were observed
as an incidential finding, GAD67 antibodies were negative at that time. After a
latency of 18 years, she manifested with refractory temporal lobe epilepsy most
likely due to autoimmune limbic encephalitis. After epilepsy onset, the patient
underwent magnetic resonance imaging (MRI), electroencephalography, cerebrospinal
fluid (CSF), serum and neuropsychological investigations during a follow-up
period of 8 years. A pharmacoresistent epilepsy with seizure onset from the right
temporal lobe and declarative memory deficits were observed affecting primarily
the recall of verbal informations. MRI showed a slightly increased signal in the
right amygdala without progression. GAD antibodies could be detected in serum
(titre 1: 1000) and CSF (titre 1:1) by immunofluorescence. Both, GAD65 and GAD67
antibodies were observed in cell-based assays. CONCLUSIONS: It can be assumed
that in addition to a pre-existing systemic T-cell response associated with the
longstanding polyendocrine autoimmunity, a delayed intrathecal autoimmunity
developed leading to limbic encephalitis. This change might be reflected by the
development of GAD67 antibodies in our patient. Besides the contribution of this
case report to a better understandig of the pathomechanisms for the development
of central nervous system (CNS) autoimmunity, it also has a clinical impact as
early treatment of GAD antibody-associated CNS disorders has a better prognosis.
Therefore, vigilance for symptoms indicating GAD antibody-associated CNS
autoimmunity is mandatory in patients with GAD antibody-associated endocrine
dysfunction.
PMID- 26420441
TI - Direct Evidence for Active Suppression of Salient-but-Irrelevant Sensory Inputs.
AB - Researchers have long debated whether attentional capture is purely stimulus
driven or purely goal driven. In the current study, we tested a hybrid account,
called the signal-suppression hypothesis, which posits that stimuli automatically
produce a bottom-up salience signal, but that this signal can be suppressed via
top-down control processes. To test this account, we used a new capture-probe
paradigm in which participants searched for a target shape while ignoring an
irrelevant color singleton. On occasional probe trials, letters were briefly
presented inside the search shapes, and participants attempted to report these
letters. Under conditions that promoted capture by the irrelevant singleton,
accuracy was greater for the letter inside the singleton distractor than for
letters inside nonsingleton distractors. However, when the conditions were
changed to avoid capture by the singleton, accuracy for the letter inside the
irrelevant singleton was reduced below the level observed for letters inside
nonsingleton distractors, an indication of active suppression of processing at
the singleton location.
PMID- 26420442
TI - Weight Discrimination and Risk of Mortality.
AB - Discrimination based on weight is a stressful social experience linked to
declines in physical and mental health. We examined whether this harmful
association extends to risk of mortality. Participants in the Health and
Retirement Study (HRS; N = 13,692) and the Midlife in the United States Study
(MIDUS; N = 5,079) reported on perceived discriminatory experiences and
attributed those experiences to a number of personal characteristics, including
weight. Weight discrimination was associated with an increase in mortality risk
of nearly 60% in both HRS participants (hazard ratio = 1.57, 95% confidence
interval = [1.34, 1.84]) and MIDUS participants (hazard ratio = 1.59, 95%
confidence interval = [1.09, 2.31]). This increased risk was not accounted for by
common physical and psychological risk factors. The association between mortality
and weight discrimination was generally stronger than that between mortality and
other attributions for discrimination. In addition to its association with poor
health outcomes, weight discrimination may shorten life expectancy.
PMID- 26420443
TI - Synthesis of Phenylene Vinylene Macrocycles through Acyclic Diene Metathesis
Macrocyclization and Their Aggregation Behavior.
AB - A series of phenylene vinylene macrocycles (PVMs) bearing substituents with
various sizes and electronic properties have been synthesized through a one-step
acyclic diene metathesis macrocyclization approach and their aggregation
behaviors have been investigated. In great contrast to the aggregation of the
analogous phenylene ethynylene macrocycles, which aggregate only when substituted
with electron-withdrawing groups, these PVMs undergo exceptionally strong
aggregation, regardless of the electron-donating or -withdrawing characters of
the substituents. The unusual aggregation behavior of the PVMs is further
investigated with thermodynamic and computer modeling studies, which show a good
agreement with the recently proposed direct through-space interaction model,
rather than the polar/pi model. The high aggregation tendency of PVMs suggests
the great potential of this novel class of shape-persistent macrocycles in a
variety of applications, such as ion channels, host-guest recognition, and
catalysis.
PMID- 26420444
TI - Experimental measurement and Monte Carlo assessment of Argon-41 production in a
PET cyclotron facility.
AB - In a medical cyclotron facility, (41)Ar (t1/2 = 109.34 m) is produced by the
activation of air due to the neutron flux during irradiation, according to the
(40)Ar(n,gamma)(41)Ar reaction; this is particularly relevant in widely diffused
high beam current cyclotrons for the production of PET radionuclides. While
theoretical estimations of the (41)Ar production have been published, no data are
available on direct experimental measurements for a biomedical cyclotron. In this
work, we describe a sampling methodology and report the results of an extensive
measurement campaign. Furthermore, the experimental results are compared with
Monte Carlo simulations performed with the FLUKA code. To measure (41)Ar
activity, air samples were taken inside the cyclotron bunker in sealed Marinelli
beakers, during the routine production of (18)F with a 16.5 MeV GE-PETtrace
cyclotron; this sampling thus reproduces a situation of absence of air changes.
Samples analysis was performed in a gamma-ray spectrometry system equipped with
HPGe detector. Monte Carlo assessment of the (41)Ar saturation yield was
performed directly using the standard FLUKA score RESNUCLE, and off-line by the
convolution of neutron fluence with cross section data. The average (41)Ar
saturation yield per one liter of air of (41)Ar, measured in gamma-ray
spectrometry, resulted to be 3.0 +/- 0.6 Bq/uA*dm(3) while simulations gave a
result of 6.9 +/- 0.3 Bq/uA*dm(3) in the direct assessment and 6.92 +/- 0.22
Bq/uA*dm(3) by the convolution neutron fluence-to-cross section.
PMID- 26420445
TI - Monte Carlo evaluation of the effect of inhomogeneities on dose calculation for
low energy photons intra-operative radiation therapy in pelvic area.
AB - The aim of this study was to evaluate the effect of inhomogeneities on dose
calculation for low energy photons intra-operative radiation therapy (IORT) in
pelvic area. A GATE Monte Carlo model of the INTRABEAM(r) was adapted for the
study. Simulations were performed in the CT scan of a cadaver considering a
homogeneous segmentation (water) and an inhomogeneous segmentation (5 tissues
from ICRU44). Measurements were performed in the cadaver using EBT3 Gafchromic(r)
films. Impact of inhomogeneities on dose calculation in cadaver was 6% for soft
tissues and greater than 300% for bone tissues. EBT3 measurements showed a better
agreement with calculation for inhomogeneous media. However, dose discrepancy in
soft tissues led to a sub-millimeter (0.65 mm) shift in the effective point dose
in depth. Except for bone tissues, the effect of inhomogeneities on dose
calculation for low energy photons intra-operative radiation therapy in pelvic
area was not significant for the studied anatomy.
PMID- 26420446
TI - Measuring skin dose in CT examinations under complex geometries: Instruments,
methods and considerations.
AB - OBJECTIVE: To investigate skin dose in Computed Tomography (CT) and its
dependence on scanning geometry. MATERIALS AND METHODS: Measurements of entrance
surface air kerma (ESAK) in free air and entrance skin dose (ESD) on an
anthropomorphic phantom were performed in a 64-slice CT scanner, using two
different instruments: the Dose Profiler (DP) and the QED skin diode (QEDSD).
Using DP and QEDSD, the ESAK rate profiles at the isocenter and at different
distances from it, were measured using axial scans. Using DP and helical scans
the ESAK rate profile in the Z-axis was acquired. The same profile was acquired
with the QEDSD also, using many axial scans and manual table translation. ESD
measurements were performed with the DP and QEDSD, in axial and helical scan
mode. RESULTS: ESAK measurements with DP and QEDSD were in good agreement, for
both point dose and profile measurements. The agreement was also good for ESD
measurements but not for helical scans, due to variable X-ray beam overlapping
and different tube angular positions at each scan start. It was observed that the
ESD values at different Y-axis offsets were comparable to the respective ESAK
values recorded at the same Y-axis offset distances without the phantom.
CONCLUSIONS: Both DP and QEDSD were proven suitable for performing point ESD
measurements. However, calculating the skin dose distribution in CT examinations
is a very challenging task. A practical approach would be for CT scanners to
provide a conservative estimate of the peak skin dose using the isocenter ESAK
value.
PMID- 26420447
TI - Did antepartum hypoxic insult caused by fetal vessel thrombosis influence the
procalcitonin level in umbilical blood? A case report.
AB - We report a case of marked elevation of the procalcitonin level in umbilical
blood and neonatal blood at birth. The mother did not perceive fetal motion.
Antepartum fetal heart rate monitoring showed a loss of variability and absence
of acceleration. No fetal breathing movement, fetal movement, or fetal tone were
observed by ultrasonography. The female neonate was delivered by cesarean section
at 25 weeks of gestation, with birthweight 774 g. The umbilical arterial pH value
at birth was 7.29. Mild elevation in interleukin-6 and tumor necrosis factor
alpha in umbilical blood were observed. Cytochrome c showed a high level in
umbilical and neonatal blood at birth. Placental histopathology revealed multiple
fetal vessel thrombosis in the large stem villi and chorionic vessels. The
neonate showed no infectious signs throughout the neonatal period. Computed
tomography at 3 months of age revealed atrophy in the cerebrum and cerebellum. At
1 year after birth, the infant showed spastic quadriplegia. In this case,
antepartum asphyxia due to fetal vessel thrombosis may have influenced the
elevation of procalcitonin level in umbilical blood and neonatal blood at birth.
PMID- 26420449
TI - Estimation of potassium and magnesium flows in animal production in Dianchi Lake
basin, China.
AB - The objectives of this study were to estimate and evaluate potassium (K) and
magnesium (Mg) budgets and flows of animal production in the basin of Dianchi
Lake, China. Feed sampling and farmer interviews were conducted in field surveys.
The supplies of K and Mg from local and external feeds and the retention,
production and excretion of animals were calculated individually for dairy cows,
fattening pigs, breeding sows, and broilers and laying hens. The K and Mg flows
on a regional level were estimated using the individual budgets. At the
individual level, in dairy cattle, the K and Mg supplied from local feeds
accounted for large parts of the total nutrient intakes, whereas in the other
animal categories most of the K and Mg in the feeds depended on external
resources. Our findings also suggested that excessive Mg intake resulted in high
Mg excretion and low use efficiency in dairy cattle and fattening pigs. At the
regional level, the K and Mg amounts of manure produced and applied in the area
(K: 339 and Mg: 143 t/year) exceeded those used as local feeds. Our results imply
the animal production potentially increased the K and Mg loads in the regional
agriculture system.
PMID- 26420448
TI - High specificity targeting and detection of human neuroblastoma using
multifunctional anti-GD2 iron-oxide nanoparticles.
AB - AIM: To develop biocompatible, tumor-specific multifunctional iron-oxide
nanoconstructs targeting neuroblastoma, an aggressive pediatric malignancy.
MATERIALS & METHODS: Clinical-grade humanized monoclonal antibody (hu14.18K322A),
designed to target GD2 antigen on neuroblastoma with reduced nonspecific immune
interactions, was conjugated to hydroxyethyl starch-coated iron-oxide
nanoparticles. Targeting capability in vitro and in vivo was assessed by
immunofluorescence, electron microscopy, analytical spectrophotometry,
histochemistry and magnetic resonance R2* relaxometry. RESULTS: The biocompatible
nanoconstructs demonstrated high tumor specificity in vitro and in vivo, and low
background uptake in a mouse flank xenograft model. Specific accumulation in
tumors enabled particle visualization and quantification by magnetic resonance
R2* mapping. CONCLUSION: Our findings support the further development toward
clinical application of this anti-GD2 iron-oxide nanoconstruct as diagnostic and
therapeutic scaffold for neuroblastoma and potentially other GD2-positive
malignancies.
PMID- 26420452
TI - Functional Conservation of Both CDS- and 3'-UTR-Located MicroRNA Binding Sites
between Species.
PMID- 26420450
TI - A web-based intervention to promote applications for rehabilitation: a study
protocol for a randomized controlled trial.
AB - BACKGROUND: The German welfare system follows the principle "rehabilitation
rather than pension," but more than the half of all disability pensioners did not
utilize medical rehabilitation before their early retirement. A major barrier is
the application procedure. Lack of information about the opportunity to utilize
rehabilitation services restricts the chance to improve work ability and to
prevent health-related early retirement by rehabilitation programs. The
establishment of new access paths to medical rehabilitation services was,
therefore, identified as a major challenge for rehabilitation research in a
recent expertise. Thus, a web-based information guide was developed to support
the application for a medical rehabilitation program. METHODS/DESIGN: For this
study, the development of a web-based information guide was based on the health
action process approach. Four modules were established. Three modules support
forming an intention by strengthening risk perception (module 1), positive
outcome expectancies (module 2) and self-efficacy (module 3). A fourth module
aims at the realization of actual behavior by offering instructions on how to
plan and to push the application process. The study on the effectiveness of the
web-based information guide will be performed as a randomized controlled trial.
Persons aged 40 to 59 years with prior sick leave benefits during the preceding
year will be included. A sample of 16,000 persons will be randomly drawn from the
registers of 3 pension insurance agencies. These persons will receive a
questionnaire to determine baseline characteristics. Respondents of this first
survey will be randomly allocated either to the intervention or the control
group. Both study groups will then receive letters with general information about
rehabilitation. The intervention group will additionally receive a link to the
web-based information guide. After 1 year, a second survey will be conducted.
Additionally, administrative data will be used to determine if participants apply
for rehabilitation and finally start a rehabilitation program. The primary
outcomes are the proportion of applied and utilized medical rehabilitation
services. Secondary outcomes are cognitions on rehabilitation, self-rated work
ability, health-related quality of life and perceived disability, as well as days
with sick leave benefits and days of regular employment. DISCUSSION: The
randomized controlled trial will provide highest ranked evidence to clarify
whether theory-driven web-based information supports access to rehabilitation
services for people with prior sickness benefits. TRIAL REGISTRATION: German
Clinical Trials Register (Identifier: DRKS00005658 , 16 January 2014).
PMID- 26420453
TI - Editorial: The public understanding of nursing--time for a step change?
PMID- 26420451
TI - Adaptive Evolution Favoring KLK4 Downregulation in East Asians.
AB - The human kallikrein (KLK) cluster, located at chromosome 19q13.3-13.4, encodes
15 serine proteases, including neighboring genes (KLK3, KLK2, KLK4, and KLK5)
with key roles in the cascades of semen liquefaction, tooth enamel maturation,
and skin desquamation. KLK2 and KLK3 were previously identified as targets of
adaptive evolution in primates through different mechanisms linked to
reproductive biology and, in humans, genome-wide scans of positive selection
captured, a yet unexplored, evidence for KLK neutrality departure in East Asians.
We perform a detailed evaluation of KLK3-KLK5 variability in the 1000 Genomes
samples from East Asia, Europe, and Africa, which was sustained by our own
sequencing. In East Asians, we singled out a 70-kb region surrounding KLK4 that
combined unusual low levels of diversity, high frequency variants with
significant levels of population differentiation (FST > 0.5) and fairly
homogenous haplotypes given the large local recombination rates. Among these
variants, rs1654556_G, rs198968_T, and rs17800874_A stand out for their location
on putative regulatory regions and predicted functional effects, namely the
introduction of several microRNA binding sites and a repressor motif. Our
functional assays carried out in different cellular models showed that rs198968_T
and rs17800874_A operate synergistically to reduce KLK4 expression and could be
further assisted by rs1654556_G. Considering the previous findings that KLK4
inactivation causes enamel malformations in humans and mice, and that this gene
is coexpressed in epidermal layers along with several substrates involved in
either cell adhesion or keratinocyte differentiation, we propose KLK4 as another
target of selection in East Asians correlated to tooth and epidermal
morphological traits.
PMID- 26420460
TI - Is the ventrogluteal site suitable for intramuscular injections in children under
the age of three?
AB - AIM: This study was conducted to determine whether the ventrogluteal site could
be used for intramuscular injections in children under the age of 3 and to
compare the subcutaneous and muscle layer thickness at the anterolateral, deltoid
and ventrogluteal site in the different age groups and in both sexes. BACKGROUND:
Although recent literature has reported that the ventrogluteal area can be an
alternative site for intramuscular injections in children <=12 months of age,
little research-based evidence has been found for the use of the ventrogluteal
site in infants and toddlers. DESIGN: A descriptive study which took place
between November 2013-August 2014. METHOD: A total of 142 children between the
ages of 1-36 months were selected by random sampling and ultrasound measurements
were made of subcutaneous and muscle thicknesses in the anterolateral, deltoid
and ventrogluteal areas. Measurements were analysed using one-way anova and
independent samples t-test. RESULTS: The subcutaneous tissue thicknesses in the
deltoid, anterolateral and ventrogluteal areas in children between 1-12 months
old (n = 56) were 5.20, 6.62 and 7.26 mm respectively, while in children between
13-24 months old (n = 42), these measurements were 4.35, 6.72 and 7.98 mm; in
children between 25-36 months old (n = 44), the measurements were 5.92, 7.97 and
13.5 mm. The muscle thicknesses in the deltoid, anterolateral and ventrogluteal
areas in children 1- 12 months old were 5.86, 9.10 and 8.17 respectively, while
in children between 13-24 months old, the measurements were 7.71, 12.92 and 17.32
mm; in children 25-36 months old, the measurements were 9.28, 18.81 and 19.62 mm.
CONCLUSION: This study found that the muscle in the ventrogluteal site is
adequately developed, even in infants between the ages of 1-12 months and that in
particular, in children 12-36 months old, the ventrogluteal site is even thicker
than the anterolateral.
PMID- 26420462
TI - N-heterocyclic carbene copper(I) catalysed N-methylation of amines using CO2.
AB - The N-methylation of amines using CO2 and PhSiH3 as source of CH3 was efficiently
performed using a N-heterocyclic carbene copper(i) complex. The methodology was
found compatible with aromatic and aliphatic primary and secondary amines.
Synthetic and computational studies have been carried out to support the proposed
reaction mechanism for this transformation.
PMID- 26420461
TI - Correlation between Echo-Tracking Parameters and In Vitro Measurements of
Arterial Contraction and Relaxation in Rats Fed a High-Cholesterol Diet.
AB - BACKGROUND: Echo-tracking (ET) is a new technique that allows the assessment of
arterial function and stiffness. This study aimed to ascertain the utility of the
echo-tracking (ET) technique to assess vascular stiffness in rats with
hypercholesterolemia and atherosclerosis. MATERIAL AND METHODS: ET was used to
measure the arterial stiffness of the aorta in cholesterol-fed Sprague-Dawley
rats (group T1, n=10, for 4 weeks; group T2, n=10, for 12 weeks) and normal
control rats (group C1, n=10; group C2, n=10). In vitro isometric tension
experiments were used to measure the maximum contractile tension (MCT) and
maximum relaxation percentage (MRR%) of aortic rings. Indicators of arterial
stiffness and aortic MCT and MRR% were compared between groups using linear
regression analysis. Light microscopic evaluation was used to demonstrate
atherosclerotic changes in the aorta. RESULTS: The rat models were successfully
induced; pathological examination of the aortas showed significant
atherosclerosis in group T2, but not in groups C1, C2, or T1. The arterial
stiffness parameters obtained using ET and aortic rings in vitro showed
significant impairments in T1 and T2 rats compared with C1 and C2 controls (all
P<0.05 vs. controls). In addition, these impairments were greater in the T2 group
than in the T1 group (all P<0.05). Finally, MRR% correlated with the
distensibility coefficient (r=0.396, P=0.012), arterial compliance (r=0.317,
P=0.047), stiffness parameter b (r=-0.406, P=0.009) and one-point pulse wave beta
(r=-0.434, P=0.005). CONCLUSIONS: These results suggest that ET could be used to
evaluate the changes in arterial wall elasticity associated with atherosclerosis
and hypercholesterolemia.
PMID- 26420463
TI - Reduction of conventional dendritic cells during Plasmodium infection is
dependent on activation induced cell death by type I and II interferons.
AB - Dendritic cells (DCs) play critical roles in innate and adaptive immunity and in
pathogenesis during the blood stage of malaria infection. The mechanisms
underlying DC homeostasis during malaria infection are not well understood. In
this study, the numbers of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in
the spleens after lethal rodent malaria infection were examined, and were found
to be significantly reduced. Concomitant with up-regulation of maturation
associated molecules, activation of caspase-3 was significantly increased,
suggesting induction of cell death. Studies using neutralizing antibody and gene
deficient mice showed that type I and II interferons were critically involved in
activation induced cell death of cDCs during malaria infection. These results
demonstrate that DCs rapidly disappeared following IFN-mediated DC activation,
and that homeostasis of DCs was significantly impaired during malaria infection.
PMID- 26420464
TI - Secondary structure of expansion segment D1 in LSU rDNA from Arachnida and its
phylogenetic application in Eriophyoid mites and in Acari.
AB - An increasing number of researchers have applied secondary-structure based
multiple alignments of rDNA genes in phylogeny. These studies mostly depended on
a few valuable divergent domains in LSU and SSU rDNA. Yet other divergent
domains, e.g. D1, were poorly investigated and rarely used. However, these
domains might contain additional evolutionary data and play a vital role in DNA
based phylogenetic study. Here, we investigated all available D1 sequences of
Arachnida taxa and predicted corresponding secondary structures to help identify
homologous positions in the D1 region. Long insertions were found exclusive to
Eriophyoidea and folded into three newly proposed helices. Non-Acari taxa were
all GC rich. In Acari, most Trombidiformes and all Mesostigmata (Parasitiformes)
taxa were AT rich and Ixodida (Parasitiformes) GC rich; however there was no
consistent base bias in Sarcoptiformes sequences. For Eriophyoid mites, genera
Cecidophyopsis and Aceria were both well supported in MP, NJ, ME and ML tress
based on D1 sequences, and clusters of Cecidophyopsis species were identical with
former study. This demonstrated that the D1 region could act as a valuable
molecular marker in phylogenetic reconstruction of Eriophyoidea. Additionally, D1
has been proven suitable in phylogenetic analysis at the family and genus level
in Acari, but not in Opiliones.
PMID- 26420465
TI - Digestion of glycogen by a glucosidase released by Trichomonas vaginalis.
AB - Trichomonas vaginalis is a protozoan parasite that is the causative agent of
trichomoniasis, a widespread sexually transmitted disease. In vitro culture of T.
vaginalis typically employs a medium supplemented with either maltose or glucose
and carbohydrates are considered essential for growth. Although the nature of the
carbohydrates utilized by T. vaginalis in vivo is undefined, the vaginal
epithelium is rich in glycogen, which appears to provide a source of carbon for
the vaginal microbiota. Here, we show that T. vaginalis grows equally well in
growth media supplemented with simple sugars or with glycogen. Analysis of
conditioned growth medium by thin layer chromatography indicates that growth on
glycogen is accompanied by glycogen breakdown to a mixture of products including
maltose, glucose, and oligosaccharides. Enzymatic assays with conditioned growth
medium show that glycogen breakdown is accomplished via the release of a
glucosidase activity having the properties of an alpha-amylase into the growth
medium. Furthermore, we find that released glucosidase activity increases upon
removal of carbohydrate from the growth medium, indicating regulation of
synthesis and/or secretion in response to environmental cues. Lastly, we show
that addition of T. vaginalis glucosidase activity to a growth medium containing
glycogen generates sufficient simple sugar to support the growth of lactobacilli
which, themselves, are unable to degrade glycogen. Thus, not only does the
glucosidase activity likely play an important role in allowing T. vaginalis to
secure simple sugars for its own use, it has the potential to impact the growth
of other members of the vaginal microbiome.
PMID- 26420466
TI - Ultrafast Fabrication of Flexible Dye-Sensitized Solar Cells by Ultrasonic Spray
Coating Technology.
AB - This study investigates novel deposition techniques for the preparation of TiO2
electrodes for use in flexible dye-sensitized solar cells. These proposed new
methods, namely pre-dye-coating and codeposition ultrasonic spraying, eliminate
the conventional need for time-consuming processes such as dye soaking and high
temperature sintering. Power conversion efficiencies of over 4.0% were achieved
with electrodes prepared on flexible polymer substrates using this new deposition
technology and N719 dye as a sensitizer.
PMID- 26420467
TI - Recombinant bacterial lipoproteins as vaccine candidates.
AB - Recombinant bacterial lipoproteins (RLP) with built-in immuno-stimulating
properties for novel subunit vaccine development are reviewed. This platform
technology offers the following advantages: easily converts antigens into highly
immunogenic RLP using a fusion sequence containing lipobox; the lipid moiety of
RLP is recognized as the danger signals in the immune system through the Toll
like receptor 2, so both innate and adaptive immune responses can be induced by
RLP; serves as an efficient and cost-effective bioprocess for producing RLP in
Escherichia coli and the feasibility and safety of this core platform technology
has been successfully demonstrated in animal model studies including
meningococcal group B subunit vaccine, dengue subunit vaccine, novel subunit
vaccine against Clostridium difficile-associated diseases and HPV-based
immunotherapeutic vaccines.
PMID- 26420468
TI - Wave-particle interaction in the Faraday waves.
AB - Wave motion in disordered Faraday waves is analysed in terms of oscillons or
quasi-particles. The motion of these oscillons is measured using particle
tracking tools and it is compared with the motion of fluid particles on the water
surface. Both the real floating particles and the oscillons, representing the
collective fluid motion, show Brownian-type dispersion exhibiting ballistic and
diffusive mean squared displacement at short and long times, respectively. While
the floating particles motion has been previously explained in the context of two
dimensional turbulence driven by Faraday waves, no theoretical description exists
for the random walk type motion of oscillons. It is found that the r.m.s velocity
?MU(osc)?(rms) of oscillons is directly related to the turbulent r.m.s. velocity
?MU?(rms) of the fluid particles in a broad range of vertical accelerations. The
measured ?MU(osc)?(rms) accurately explains the broadening of the frequency
spectra of the surface elevation observed in disordered Faraday waves. These
results suggest that 2D turbulence is the driving force behind both the
randomization of the oscillons motion and the resulting broadening of the wave
frequency spectra. The coupling between wave motion and hydrodynamic turbulence
demonstrated here offers new perspectives for predicting complex fluid transport
from the knowledge of wave field spectra and vice versa.
PMID- 26420469
TI - What Online Communities Can Tell Us About Electronic Cigarettes and Hookah Use: A
Study Using Text Mining and Visualization Techniques.
AB - BACKGROUND: The rise in popularity of electronic cigarettes (e-cigarettes) and
hookah over recent years has been accompanied by some confusion and uncertainty
regarding the development of an appropriate regulatory response towards these
emerging products. Mining online discussion content can lead to insights into
people's experiences, which can in turn further our knowledge of how to address
potential health implications. In this work, we take a novel approach to
understanding the use and appeal of these emerging products by applying text
mining techniques to compare consumer experiences across discussion forums.
OBJECTIVE: This study examined content from the websites Vapor Talk, Hookah
Forum, and Reddit to understand people's experiences with different tobacco
products. Our investigation involves three parts. First, we identified contextual
factors that inform our understanding of tobacco use behaviors, such as setting,
time, social relationships, and sensory experience, and compared the forums to
identify the ones where content on these factors is most common. Second, we
compared how the tobacco use experience differs with combustible cigarettes and e
cigarettes. Third, we investigated differences between e-cigarette and hookah
use. METHODS: In the first part of our study, we employed a lexicon-based
extraction approach to estimate prevalence of contextual factors, and then we
generated a heat map based on these estimates to compare the forums. In the
second and third parts of the study, we employed a text mining technique called
topic modeling to identify important topics and then developed a visualization,
Topic Bars, to compare topic coverage across forums. RESULTS: In the first part
of the study, we identified two forums, Vapor Talk Health & Safety and the
Stopsmoking subreddit, where discussion concerning contextual factors was
particularly common. The second part showed that the discussion in Vapor Talk
Health & Safety focused on symptoms and comparisons of combustible cigarettes and
e-cigarettes, and the Stopsmoking subreddit focused on psychological aspects of
quitting. Last, we examined the discussion content on Vapor Talk and Hookah
Forum. Prominent topics included equipment, technique, experiential elements of
use, and the buying and selling of equipment. CONCLUSIONS: This study has three
main contributions. Discussion forums differ in the extent to which their content
may help us understand behaviors with potential health implications. Identifying
dimensions of interest and using a heat map visualization to compare across
forums can be helpful for identifying forums with the greatest density of health
information. Additionally, our work has shown that the quitting experience can
potentially be very different depending on whether or not e-cigarettes are used.
Finally, e-cigarette and hookah forums are similar in that members represent a
"hobbyist culture" that actively engages in information exchange. These
differences have important implications for both tobacco regulation and smoking
cessation intervention design.
PMID- 26420470
TI - A promising way to open an energy gap in bilayer graphene.
AB - There has been huge research interest in the energy gap problem of monolayer and
bilayer graphene due to their great potential in practical applications. Herein,
based on first-principles calculations, we report a promising way to open a large
band gap in bilayer graphene (BLG) by sandwiching it between two substrates,
although this is not usually expected to occur due to the weak interlayer
interactions dominated by van der Waals forces. Taking surface-functionalized
boron-nitrides as substrates, we predict from first-principles calculations that
BLG can have energy gaps ranging from 0.35 eV to 0.55 eV, depending on the
substrates and stacking order. Compared to other methods of band-gap manipulation
in BLG, the structural integrity of BLG is well-preserved in our study, and the
predicted energy gap is suitable for electric devices. Since the proposed method
is easily realized in experiments, our results will hopefully accelerate the
application of graphene in semiconductor devices and promote the development of
graphene technology.
PMID- 26420471
TI - Measuring health-relevant businesses over 21 years: refining the National
Establishment Time-Series (NETS), a dynamic longitudinal data set.
AB - BACKGROUND: The densities of food retailers, alcohol outlets, physical activity
facilities, and medical facilities have been associated with diet, physical
activity, and management of medical conditions. Most of the research, however,
has relied on cross-sectional studies. In this paper, we assess methodological
issues raised by a data source that is increasingly used to characterize change
in the local business environment: the National Establishment Time Series (NETS)
dataset. DISCUSSION: Longitudinal data, such as NETS, offer opportunities to
assess how differential access to resources impacts population health, to
consider correlations among multiple environmental influences across the life
course, and to gain a better understanding of their interactions and cumulative
health effects. Longitudinal data also introduce new data management,
geoprocessing, and business categorization challenges. Examining geocoding
accuracy and categorization over 21 years of data in 23 counties surrounding New
York City (NY, USA), we find that health-related business environments change
considerably over time. We note that re-geocoding data may improve spatial
precision, particularly in early years. Our intent with this paper is to make
future public health applications of NETS data more efficient, since the size and
complexity of the data can be difficult to exploit fully within its 2-year data
licensing period. Further, standardized approaches to NETS and other "big data"
will facilitate the veracity and comparability of results across studies.
PMID- 26420472
TI - Computational Design of Oligopeptide Containing Poly(ethylene glycol) Brushes for
Stimuli-Responsive Drug Delivery.
AB - Stimuli-responsive biomaterials are used to facilitate drug and gene delivery by
shielding the drug/gene during circulation times and selectively releasing the
cargo at the desired target. Within stimuli-responsive materials, pH-responsive
materials are exploited for delivery to specific organs, intracellular
compartments, cancer cells, site of inflammation or infection as those sites are
characterized by pH that is different from the blood pH. In this paper we use
molecular dynamics (MD) simulations to design such pH-responsive biomaterials
where the balance between the various intermolecular interactions (e.g.,
electrostatics, van der Waals) within the biomaterials allow biofunctional
molecules to be reversibly shielded and exposed to the environment with change in
pH. In our model the shielding aspect is imparted by a polyethylene glycol (PEG)
brush and the pH-responsive component is a PEG-tethered oligopeptide that
undergoes changes in conformations via protonation of residues upon changes in
pH. Starting with a PEG-tethered peptide in a monodisperse short PEG brush, we
first vary the composition and sequence of histidine (H), lysine (K), and
glutamate (E) along the oligopeptide sequence to find the design parameters that
maximize the shielding and exposure of the oligopeptide at pH ~ 7.0 and pH < 7.0,
respectively. Then, we probe the effect of the PEG brush on the conformations of
the oligopeptides by simulating PEG-tethered peptide in a bimodal PEG brush
containing short PEG and long PEG chains. We characterize the intermolecular
interactions involving the PEG, peptide, and solvent that influence the shielded
and exposed conformations of the oligopeptides at the two different pHs. In a
short monodisperse PEG brush, with a longer PEG-tethered peptide containing large
blocks of histidines that undergo change in protonation state as a response to pH
change, placed between a protonated lysine and deprotonated glutamate, the PEG
brush exhibits maximum shielding and exposure with pH change. This change from
shielded to exposed state is driven by electrostatic repulsion upon H
protonation. The presence of long PEG chains in a bimodal PEG brush leads to
dominating PEG-peptide attractive interactions that reduces the contrast in
shielded and exposed conformations of the PEG-tethered peptide upon protonation
of histidines.
PMID- 26420473
TI - Preoperative transcutaneous electrical nerve stimulation for localizing
superficial nerve paths.
AB - During surgery, peripheral nerves are often seen to follow unpredictable paths
because of previous surgeries and/or compression caused by a tumor. Iatrogenic
nerve injury is a serious complication that must be avoided, and preoperative
evaluation of nerve paths is important for preventing it. In this study,
transcutaneous electrical nerve stimulation (TENS) was used for an in-depth
analysis of peripheral nerve paths. This study included 27 patients who underwent
the TENS procedure to evaluate the peripheral nerve path (17 males and 10
females; mean age: 59.9 years, range: 18-83 years) of each patient
preoperatively. An electrode pen coupled to an electrical nerve stimulator was
used for superficial nerve mapping. The TENS procedure was performed on patients'
major peripheral nerves that passed close to the surgical field of tumor
resection or trauma surgery, and intraoperative damage to those nerves was
apprehensive. The paths of the target nerve were detected in most patients
preoperatively. The nerve paths of 26 patients were precisely under the markings
drawn preoperatively. The nerve path of one patient substantially differed from
the preoperative markings with numbness at the surgical region. During surgery,
the nerve paths could be accurately mapped preoperatively using the TENS
procedure as confirmed by direct visualization of the nerve. This stimulation
device is easy to use and offers highly accurate mapping of nerves for surgical
planning without major complications. The authors conclude that TENS is a useful
tool for noninvasive nerve localization and makes tumor resection a safe and
smooth procedure.
PMID- 26420474
TI - Long-term outcome of free fibula osteocutaneous flap and massive allograft in the
reconstruction of long bone defect.
AB - Reconstruction of massive bone defects in bone tumors with allografts has been
shown to have significant complications including infection, delayed or nonunion
of allograft, and allograft fracture. Resection compounded with soft tissue
defects requires skin coverage. A composite osteocutaneous free fibula offers an
optimal solution where the allografts can be augmented mechanically and achieve
biological incorporation. Following resection, the cutaneous component of the
free osteocutaneous fibula flaps covers the massive soft tissue defect. In this
retrospective study, the long-term outcome of 12 patients, who underwent single
stage limb reconstruction with massive allograft and free fibula osteocutaneous
flaps instead of free fibula osteal flaps only, was evaluated. This study
included 12 consecutive patients who had primary bone tumors and had follow-up
for a minimum of 24 months. The mean age at the time of surgery was 19.8 years. A
total of eight patients had primary malignant bone tumors (five osteosarcomas,
two chondrosarcomas and one synovial sarcoma), and four patients had benign bone
tumors (two giant-cell tumors, one aneurysmal bone cyst, and one
neurofibromatosis). The mean follow-up for the 12 patients was 63 months (range
24-124 months). Out of the 10 patients, nine underwent lower-limb reconstruction
and ambulated with partial weight bearing and full weight bearing at an average
of 4.2 months and 8.2 months, respectively. In conclusion, augmentation of a
massive allograft with free fibula osteocutaneous flap is an excellent
alternative for reducing the long-term complication of massive allograft and
concurrently addresses the soft tissue coverage.
PMID- 26420476
TI - Resolving the conundrum of inbreeding depression but no inbreeding avoidance:
Estimating sex-specific selection on inbreeding by song sparrows (Melospiza
melodia).
AB - Inbreeding avoidance among interacting females and males is not always observed
despite inbreeding depression in offspring fitness, creating an apparent
"inbreeding paradox." This paradox could be resolved if selection against
inbreeding was in fact weak, despite inbreeding depression. However, the net
magnitude and direction of selection on the degree to which females and males
inbreed by pairing with relatives has not been explicitly estimated. We used long
term pedigree data to estimate phenotypic selection gradients on the degree of
inbreeding that female and male song sparrows (Melospiza melodia) expressed by
forming socially persistent breeding pairs with relatives. Fitness was measured
as the total numbers of offspring and grand offspring contributed to the
population, and as corresponding expected numbers of identical-by-descent allele
copies, thereby accounting for variation in offspring survival, reproduction, and
relatedness associated with variation in parental inbreeding. Estimated selection
gradients on the degree to which individuals paired with relatives were weakly
positive in females, but negative in males that formed at least one socially
persistent pairing. However, males that paired had higher mean fitness than males
that remained socially unpaired. These analyses suggest that net selection
against inbreeding may be weak in both sexes despite strong inbreeding
depression, thereby resolving the "inbreeding paradox."
PMID- 26420477
TI - Rare genomic rearrangement in a boy with Williams-Beuren syndrome associated to
XYY syndrome and intriguing behavior.
AB - Williams-Beuren syndrome (WBS) is caused by a hemizygous contiguous gene
microdeletion of 1.55-1.84 Mb at 7q11.23 region. Approximately, 28 genes have
been shown to contribute to classical phenotype of SWB with presence of
dysmorphic facial features, supravalvular aortic stenosis (SVAS), intellectual
disability, and overfriendliness. With the use of Microarray-based comparative
genomic hybridization and other molecular cytogenetic techniques, is possible
define with more accuracy partial or atypical deletion and refine the genotype
phenotype correlation. Here, we report on a rare genomic structural rearrangement
in a boy with atypical deletion in 7q11.23 and XYY syndrome with characteristic
clinical signs, but not sufficient for the diagnosis of WBS. Cytogenetic analysis
of G-banding showed a karyotype 47,XYY. Analysis of DNA with the technique of
MLPA (Multiplex Ligation-dependent Probe Amplification) using kits a combination
of kits (P064, P036, P070, and P029) identified an atypical deletion on 7q11.23.
In addition, high resolution SNP Oligonucleotide Microarray Analysis (SNP-array)
confirmed the alterations found by MLPA and revealed others pathogenic CNVs, in
the chromosomes 7 and X. The present report demonstrates an association not yet
described in literature, between Williams-Beuren syndrome and 47,XYY. The
identification of atypical deletion in 7q11.23 concomitant to additional
pathogenic CNVs in others genomic regions allows a better comprehension of
clinical consequences of atypical genomic rearrangements.
PMID- 26420475
TI - Gossypium barbadense genome sequence provides insight into the evolution of extra
long staple fiber and specialized metabolites.
AB - Of the two cultivated species of allopolyploid cotton, Gossypium barbadense
produces extra-long fibers for the production of superior textiles. We sequenced
its genome (AD)2 and performed a comparative analysis. We identified three bursts
of retrotransposons from 20 million years ago (Mya) and a genome-wide uneven
pseudogenization peak at 11-20 Mya, which likely contributed to genomic
divergences. Among the 2,483 genes preferentially expressed in fiber, a cell
elongation regulator, PRE1, is strikingly At biased and fiber specific, echoing
the A-genome origin of spinnable fiber. The expansion of the PRE members implies
a genetic factor that underlies fiber elongation. Mature cotton fiber consists of
nearly pure cellulose. G. barbadense and G. hirsutum contain 29 and 30 cellulose
synthase (CesA) genes, respectively; whereas most of these genes (>25) are
expressed in fiber, genes for secondary cell wall biosynthesis exhibited a
delayed and higher degree of up-regulation in G. barbadense compared with G.
hirsutum, conferring an extended elongation stage and highly active secondary
wall deposition during extra-long fiber development. The rapid diversification of
sesquiterpene synthase genes in the gossypol pathway exemplifies the chemical
diversity of lineage-specific secondary metabolites. The G. barbadense genome
advances our understanding of allopolyploidy, which will help improve cotton
fiber quality.
PMID- 26420479
TI - Interleukin-29 induces receptor activator of NF-kappaB ligand expression in
fibroblast-like synoviocytes via MAPK signaling pathways.
AB - AIM: We previously reported that interleukin-29 (IL-29) was highly expressed in
the blood and synovium of rheumatoid arthritis (RA) patients and contributed to
synovial inflammation by induction of proinflammatory cytokine production. Given
chronic inflammation can trigger the process of bone erosion, and receptor
activator of nuclear factor-kappaB ligand (RANKL) plays a crucial role in bone
erosion of RA, we hypothesize that IL-29 mediates bone erosion in RA by
regulation of RANKL expression. Here, we investigated the effect of IL-29 on
RANKL expression in RA fibroblast-like synoviocytes (FLS) and the relevant
signaling pathways involved in it. METHODS: Primary fibroblast cells isolated
from RA patients were stimulated by recombinant IL-29 in the presence or absence
of anti-IL-29 antibody, and the expression levels of RANKL were assessed using
real-time polymerase chain reaction and immunostaining. Furthermore, the IL-29
signaling pathway for regulation of RANKL was also examined by Western blotting
assay. RESULTS: IL-29 upregulated RANKL expression in a dose-dependent manner,
and blockade of IL-29 resulted in a significantly reduced RANKL expression in RA
FLS. Incubation RA-FLS with IL-29 (100 ng/mL) led to phosphorylation of ERK
(extracellular signal-regulated kinase), p38 and JNK (c-Jun N-terminal kinase).
The expression of RANKL induced by IL-29 could be completely blocked by the
inhibitors of mitogen-activated protein kinase (MAPK) signal pathway, including
PD98059 (ERK inhibitor), SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor).
CONCLUSION: These findings indicate, for the first time, that IL-29 could
directly induce RANKL expression in RA-FLS via MAPK signaling pathway, suggesting
IL-29 might be a new target in the prevention of joint destruction in RA.
PMID- 26420480
TI - Printable Bioelectronics To Investigate Functional Biological Interfaces.
AB - Thin-film transistors can be used as high-performance bioelectronic devices to
accomplish tasks such as sensing or controlling the release of biological species
as well as transducing the electrical activity of cells or even organs, such as
the brain. Organic, graphene, or zinc oxide are used as convenient printable
semiconducting layers and can lead to high-performance low-cost bioelectronic
sensing devices that are potentially very useful for point-of-care applications.
Among others, electrolyte-gated transistors are of interest as they can be
operated as capacitance-modulated devices, because of the high capacitance of
their charge double layers. Specifically, it is the capacitance of the biolayer,
being lowest in a series of capacitors, which controls the output current of the
device. Such an occurrence allows for extremely high sensitivity towards very
weak interactions. All the aspects governing these processes are reviewed here.
PMID- 26420481
TI - The Kaposi Sarcoma Herpesvirus Latency-associated Nuclear Antigen DNA Binding
Domain Dorsal Positive Electrostatic Patch Facilitates DNA Replication and
Episome Persistence.
AB - Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several
human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates
persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA
replication and segregates episomes to progeny nuclei. The structure of the LANA
DNA binding domain was recently solved, revealing a positive electrostatic patch
opposite the DNA binding surface, which is the site of BET protein binding. Here
we investigate the functional role of the positive patch in LANA-mediated episome
persistence. As expected, LANA mutants with alanine or glutamate substitutions in
the central, peripheral, or lateral portions of the positive patch maintained the
ability to bind DNA by EMSA. However, all of the substitution mutants were
deficient for LANA DNA replication and episome maintenance. Mutation of the
peripheral region generated the largest deficiencies. Despite these deficiencies,
all positive patch mutants concentrated to dots along mitotic chromosomes in
cells containing episomes, similar to LANA. The central and peripheral mutants,
but not the lateral mutants, were reduced for BET protein interaction as assessed
by co-immunoprecipitation. However, defects in BET protein binding were
independent of episome maintenance function. Overall, the reductions in episome
maintenance closely correlated with DNA replication deficiencies, suggesting that
the replication defects account for the reduced episome persistence. Therefore,
the electrostatic patch exerts a key role in LANA-mediated DNA replication and
episome persistence and may act through a host cell partner(s) other than a BET
protein or by inducing specific structures or complexes.
PMID- 26420482
TI - Structural Basis for Ligand Recognition and Functional Selectivity at Angiotensin
Receptor.
AB - Angiotensin II type 1 receptor (AT1R) is the primary blood pressure regulator.
AT1R blockers (ARBs) have been widely used in clinical settings as anti
hypertensive drugs and share a similar chemical scaffold, although even minor
variations can lead to distinct therapeutic efficacies toward cardiovascular
etiologies. The structural basis for AT1R modulation by different peptide and non
peptide ligands has remained elusive. Here, we report the crystal structure of
the human AT1R in complex with an inverse agonist olmesartan (Benicar(TM)), a
highly potent anti-hypertensive drug. Olmesartan is anchored to the receptor
primarily by the residues Tyr-35(1.39), Trp-84(2.60), and Arg-167(ECL2), similar
to the antagonist ZD7155, corroborating a common binding mode of different ARBs.
Using docking simulations and site-directed mutagenesis, we identified specific
interactions between AT1R and different ARBs, including olmesartan derivatives
with inverse agonist, neutral antagonist, or agonist activities. We further
observed that the mutation N111(3.35)A in the putative sodium-binding site
affects binding of the endogenous peptide agonist angiotensin II but not the beta
arrestin-biased peptide TRV120027.
PMID- 26420483
TI - Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in
an Amyloid-beta Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3
Kinase (PI3K)/Akt/Wnt/beta-Catenin Pathway.
AB - Neurogenesis involves generation of new neurons through finely tuned multistep
processes, such as neural stem cell (NSC) proliferation, migration,
differentiation, and integration into existing neuronal circuitry in the dentate
gyrus of the hippocampus and subventricular zone. Adult hippocampal neurogenesis
is involved in cognitive functions and altered in various neurodegenerative
disorders, including Alzheimer disease (AD). Ethosuximide (ETH), an
anticonvulsant drug is used for the treatment of epileptic seizures. However, the
effects of ETH on adult hippocampal neurogenesis and the underlying cellular and
molecular mechanism(s) are yet unexplored. Herein, we studied the effects of ETH
on rat multipotent NSC proliferation and neuronal differentiation and adult
hippocampal neurogenesis in an amyloid beta (Abeta) toxin-induced rat model of AD
like phenotypes. ETH potently induced NSC proliferation and neuronal
differentiation in the hippocampus-derived NSC in vitro. ETH enhanced NSC
proliferation and neuronal differentiation and reduced Abeta toxin-mediated
toxicity and neurodegeneration, leading to behavioral recovery in the rat AD
model. ETH inhibited Abeta-mediated suppression of neurogenic and Akt/Wnt/beta
catenin pathway gene expression in the hippocampus. ETH activated the PI3K.Akt
and Wnt.beta-catenin transduction pathways that are known to be involved in the
regulation of neurogenesis. Inhibition of the PI3K.Akt and Wnt.beta-catenin
pathways effectively blocked the mitogenic and neurogenic effects of ETH. In
silico molecular target prediction docking studies suggest that ETH interacts
with Akt, Dkk-1, and GSK-3beta. Our findings suggest that ETH stimulates NSC
proliferation and differentiation in vitro and adult hippocampal neurogenesis via
the PI3K.Akt and Wnt.beta-catenin signaling.
PMID- 26420484
TI - Histone Deacetylase 3 Coordinates Deacetylase-independent Epigenetic Silencing of
Transforming Growth Factor-beta1 (TGF-beta1) to Orchestrate Second Heart Field
Development.
AB - About two-thirds of human congenital heart disease involves second heart field
derived structures. Histone-modifying enzymes, histone deacetylases (HDACs),
regulate the epigenome; however, their functions within the second heart field
remain elusive. Here we demonstrate that histone deacetylase 3 (HDAC3)
orchestrates epigenetic silencing of Tgf-beta1, a causative factor in congenital
heart disease pathogenesis, in a deacetylase-independent manner to regulate
development of second heart field-derived structures. In murine embryos lacking
HDAC3 in the second heart field, increased TGF-beta1 bioavailability is
associated with ascending aortic dilatation, outflow tract malrotation,
overriding aorta, double outlet right ventricle, aberrant semilunar valve
development, bicuspid aortic valve, ventricular septal defects, and embryonic
lethality. Activation of TGF-beta signaling causes aberrant endothelial-to
mesenchymal transition and altered extracellular matrix homeostasis in HDAC3-null
outflow tracts and semilunar valves, and pharmacological inhibition of TGF-beta
rescues these defects. HDAC3 recruits components of the PRC2 complex,
methyltransferase EZH2, EED, and SUZ12, to the NCOR complex to enrich
trimethylation of Lys-27 on histone H3 at the Tgf-beta1 regulatory region and
thereby maintains epigenetic silencing of Tgf-beta1 specifically within the
second heart field-derived mesenchyme. Wild-type HDAC3 or catalytically inactive
HDAC3 expression rescues aberrant endothelial-to-mesenchymal transition and
epigenetic silencing of Tgf-beta1 in HDAC3-null outflow tracts and semilunar
valves. These findings reveal that epigenetic dysregulation within the second
heart field is a predisposing factor for congenital heart disease.
PMID- 26420485
TI - Retinal Degeneration Slow (RDS) Glycosylation Plays a Role in Cone Function and
in the Regulation of RDS.ROM-1 Protein Complex Formation.
AB - The photoreceptor-specific glycoprotein retinal degeneration slow (RDS, also
called PRPH2) is necessary for the formation of rod and cone outer segments.
Mutations in RDS cause rod and cone-dominant retinal disease, and it is well
established that both cell types have different requirements for RDS. However,
the molecular mechanisms for this difference remain unclear. Although RDS
glycosylation is highly conserved, previous studies have revealed no apparent
function for the glycan in rods. In light of the highly conserved nature of RDS
glycosylation, we hypothesized that it is important for RDS function in cones and
could underlie part of the differential requirement for RDS in the two
photoreceptor subtypes. We generated a knockin mouse expressing RDS without the N
glycosylation site (N229S). Normal levels of RDS and the unglycosylated RDS
binding partner rod outer segment membrane protein 1 (ROM-1) were found in N229S
retinas. However, cone electroretinogram responses were decreased by 40% at 6
months of age. Because cones make up only 3-5% of photoreceptors in the wild-type
background, N229S mice were crossed into the nrl(-/-) background (in which all
rods are converted to cone-like cells) for biochemical analysis. In N229S/nrl(-/
) retinas, RDS and ROM-1 levels were decreased by ~60% each. These data suggest
that glycosylation of RDS is required for RDS function or stability in cones, a
difference that may be due to extracellular versus intradiscal localization of
the RDS glycan in cones versus rods.
PMID- 26420488
TI - Biomarkers in Child Mental Health: a bio-psycho-social perspective is needed.
PMID- 26420486
TI - ATM-dependent Phosphorylation of the Fanconi Anemia Protein PALB2 Promotes the
DNA Damage Response.
AB - The Fanconi anemia protein PALB2, also known as FANCN, protects genome integrity
by regulating DNA repair and cell cycle checkpoints. Exactly how PALB2 functions
may be temporally coupled with detection and signaling of DNA damage is not
known. Intriguingly, we found that PALB2 is transformed into a
hyperphosphorylated state in response to ionizing radiation (IR). IR treatment
specifically triggered PALB2 phosphorylation at Ser-157 and Ser-376 in manners
that required the master DNA damage response kinase Ataxia telangiectasia
mutated, revealing potential mechanistic links between PALB2 and the Ataxia
telangiectasia mutated-dependent DNA damage responses. Consistently, dysregulated
PALB2 phosphorylation resulted in sustained activation of DDRs. Full-blown PALB2
phosphorylation also required the breast and ovarian susceptible gene product
BRCA1, highlighting important roles of the BRCA1-PALB2 interaction in
orchestrating cellular responses to genotoxic stress. In summary, our
phosphorylation analysis of tumor suppressor protein PALB2 uncovers new layers of
regulatory mechanisms in the maintenance of genome stability and tumor
suppression.
PMID- 26420487
TI - Innervating sympathetic neurons regulate heart size and the timing of
cardiomyocyte cell cycle withdrawal.
AB - Sympathetic drive to the heart is a key modulator of cardiac function and
interactions between heart tissue and innervating sympathetic fibres are
established early in development. Significant innervation takes place during
postnatal heart development, a period when cardiomyocytes undergo a rapid
transition from proliferative to hypertrophic growth. The question of whether
these innervating sympathetic fibres play a role in regulating the modes of
cardiomyocyte growth was investigated using 6-hydroxydopamine (6-OHDA) to abolish
early sympathetic innervation of the heart. Postnatal chemical sympathectomy
resulted in rats with smaller hearts, indicating that heart growth is regulated
by innervating sympathetic fibres during the postnatal period. In vitro
experiments showed that sympathetic interactions resulted in delays in markers of
cardiomyocyte maturation, suggesting that changes in the timing of the transition
from hyperplastic to hypertrophic growth of cardiomyocytes could underlie changes
in heart size in the sympathectomized animals. There was also an increase in the
expression of Meis1, which has been linked to cardiomyocyte cell cycle
withdrawal, suggesting that sympathetic signalling suppresses cell cycle
withdrawal. This signalling involves beta-adrenergic activation, which was
necessary for sympathetic regulation of cardiomyocyte proliferation and
hypertrophy. The effect of beta-adrenergic signalling on cardiomyocyte
hypertrophy underwent a developmental transition. While young postnatal
cardiomyocytes responded to isoproterenol (isoprenaline) with a decrease in cell
size, mature cardiomyocytes showed an increase in cell size in response to the
drug. Together, these results suggest that early sympathetic effects on
proliferation modulate a key transition between proliferative and hypertrophic
growth of the heart and contribute to the sympathetic regulation of adult heart
size.
PMID- 26420489
TI - The Effects of Interpreter Use on Agreement Between Clinician- and Self-Ratings
of Functioning in Hispanic Integrated Care Patients.
AB - This study explored whether concordance between self- and clinician- assessment
of functioning differs when an interpreter is used in therapy versus when there
is language congruence between the clinician and the patient, and whether
concordance is affected by patient distress. Participants were 418 Spanish
speaking patients seen at one of three primary care clinics. Patients were
primarily Hispanic (94 %), uninsured (65 %), and female (84 %), and ranged in age
from 18 to 73 years (M = 41.70, SD = 10.70). Pearson's correlation coefficients
assessed the association between self- and clinician- reports of patient
functioning with and without use of an interpreter. Fisher's z transformations
assessed the significance of the difference between the correlation coefficients.
Although interpreter use did not significantly disrupt communication of
functioning when the patient was highly distressed, there was significant
discordance in clinician and patient reports in patients experiencing milder
levels of distress communicating by means of an interpreter.
PMID- 26420490
TI - Disparities in Health Services Use Among Multiracial American Young Adults.
AB - Addressing disparities in health services utilization remains critical for
improving minority health; however, most studies do not report on the health
service use of multiracial young adults (age 22-34). This study compares past
year health service use of self-identified multiracial (two or more races) young
adults with monoracial White young adults. Weighted survey data from Add Health
(N = 7296) and multivariate logistic regression analyses were used. Compared to
monoracial White young adults, Black-White multiracial [OR 0.40, 95 % CI (0.17
0.90)] and Black-Native American multiracial [OR 0.23, 95 % CI (0.09-0.63)] young
adults are less likely to report primary care service use in the past year.
Multiracial young adults have different health care service utilization than
their White monoracial peers with Black-Native American young adults appearing to
be particularly vulnerable to under-utilization of primary care services. It is
important to examine multiracial subgroups when studying patterns of health
services utilization.
PMID- 26420492
TI - Caregiver Well-Being: Is it On Your Radar?
PMID- 26420491
TI - A low-dose, dual-phase cardiovascular CT protocol to assess left atrial appendage
anatomy and exclude thrombus prior to left atrial intervention.
AB - Assessment of the left atrial appendage (LAA) for thrombus and anatomy is
important prior to atrial fibrillation (AF) ablation and LAA exclusion. The use
of cardiovascular CT (CCT) to detect LAA thrombus has been limited by the high
incidence of pseudothrombus on single-pass studies. We evaluated the diagnostic
accuracy of a two-phase protocol incorporating a limited low-dose delayed
contrast-enhanced examination of the LAA, compared with a single-pass study for
LAA morphological assessment, and transesophageal echocardiography (TEE) for the
exclusion of thrombus. Consecutive patients (n = 122) undergoing left atrial
interventions for AF were assessed. All had a two-phase CCT protocol (first-past
scan plus a limited, 60-s delayed scan of the LAA) and TEE. Sensitivity,
specificity, diagnostic accuracy, positive (PPV) and negative predictive values
(NPV) were calculated for the detection of true thrombus on first-pass and
delayed scans, using TEE as the gold standard. Overall, 20/122 (16.4 %) patients
had filling defects on the first-pass study. All affected the full delineation of
the LAA morphology; 17/20 (85 %) were confirmed as pseudo-filling defects. Three
(15 %) were seen on late-pass and confirmed as true thrombi on TEE; a significant
improvement in diagnostic performance relative to a single-pass scan (McNemar Chi
square 17, p < 0.001). The sensitivity, specificity, diagnostic accuracy, PPV and
NPV was 100, 85.7, 86.1, 15.0 and 100 % respectively for first-pass scans, and
100 % for all parameters for the delayed scans. The median (range) additional
radiation dose for the delayed scan was 0.4 (0.2-0.6) mSv. A low-dose delayed
scan significantly improves the identification of true LAA anatomy and thrombus
in patients undergoing LA intervention.
PMID- 26420493
TI - Reply to the Letter to the Editor by O'Caoimh et al.
PMID- 26420494
TI - Pioneering a Nursing Home Quality Improvement Learning Collaborative: A Case
Study of Method and Lessons Learned.
AB - OBJECTIVES: To describe the development of a nursing home (NH) quality
improvement learning collaborative (QILC) that provides Lean Six Sigma (LSS)
training and infrastructure support for quality assurance performance improvement
change efforts. DESIGN: Case report. SETTING/PARTICIPANTS: Twenty-seven NHs
located in the Greater Rochester, NY area. INTERVENTION: The learning
collaborative approach in which interprofessional teams from different NHs work
together to improve common clinical and organizational processes by sharing
experiences and evidence-based practices to achieve measurable changes in
resident outcomes and system efficiencies. MEASUREMENTS: NH participation,
curriculum design, LSS projects. RESULTS: Over 6 years, 27 NHs from urban and
rural settings joined the QILC as organizational members and sponsored 47
interprofessional teams to learn LSS techniques and tools, and to implement
quality improvement projects. CONCLUSIONS: NHs, in both urban and rural settings,
can benefit from participation in QILCs and are able to learn and apply LSS tools
in their team-based quality improvement efforts.
PMID- 26420495
TI - Leucobacter zeae sp. nov., isolated from the rhizosphere of maize (Zea mays L.).
AB - A novel yellow-pigmented, aerobic, rod-shaped, non-motile bacterium, designated
strain CCMF41T, was isolated from rhizosphere soil of maize (Zea mays) collected
in Wufeng District, Taichung, Taiwan. Strain CC-MF41T exhibited 16S rRNA gene
sequence similarity of 97.5, 97.3, 97.2 and 97.1% to Leucobacter chironomi MM2LBT
(and 'Leucobacter kyeonggiensis'F3-P9 and 'L. humi' Re-6, the names of which have
not been validly published), Leucobactertardus K70/01T, L. komagatae IFO 15245T
and 'Leucobacter margaritiformis' A23. However,CC-MF41T and 'L. margaritiformis'
A23 formed a loosely bound phylogenetic lineage (with alow bootstrap value)
associated with species of the genus Leucobacter. In DNA-DNA reassociation
experiments, the relatedness of strain CC-MF41T to L. chironomi DSM 19883T was
57.1% (reciprocal value 29.1 %). The DNA G+C content of strain CC-MF41T was 72.1
mol% and the cell-wall peptidoglycan contained 2,4-diaminobutyric acid, alanine,
glycine,glutamic acid and threonine. The major menaquinone was MK-11 and the
predominant fatty acids were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0.
The polar lipid profile of strain CCMF41T contained major amounts of
diphosphatidylglycerol followed by an unidentified glycolipid,
phosphatidylglycerol and an unknown phospholipid. Based on its
phylogenetic,phenotypic and chemotaxonomic distinctiveness, strain CC-MF41T
represents a novel species of Leucobacter, for which the name Leucobacter zeae
sp. nov. is proposed. The type strain isCC-MF41T (=BCRC 80515T=LMG 27265T).
PMID- 26420496
TI - Effect of co-ingestion of amino acids with rice on glycaemic and insulinaemic
response.
AB - Consumption of high glycaemic index (GI) and glycaemic response (GR) food such as
white rice has been implicated in the development of type 2 diabetes. Previous
studies have reported the ability of individual amino acids to reduce GR of
carbohydrate-rich foods. Because of the bitter flavour of amino acids, they have
rarely been used to reduce GR. We now report the use of a palatable, preformed
amino acid mixture in the form of essence of chicken. In all, sixteen healthy
male Chinese were served 68 or 136 ml amino acid mixture together with rice, or
15 or 30 min before consumption of white rice. Postprandial blood glucose and
plasma insulin concentrations were measured at fasting and every 15 min after
consumption of the meal until 60 min after the consumption of the white rice.
Subsequent blood samples were taken at 30-min intervals until 210 min. The co
ingestion of 68 ml of amino acid mixture with white rice produced the best
results in reducing the peak blood glucose and GR of white rice without
increasing the insulinaemic response. It is postulated that amino acid mixtures
prime beta-cell insulin secretion and peripheral tissue uptake of glucose. The
use of ready-to-drink amino acid mixtures may be a useful strategy for lowering
the high-GI rice diets consumed in Asia.
PMID- 26420497
TI - Mandatory implementation of NICE Guidelines for the care of bipolar disorder and
other conditions in England and Wales.
AB - BACKGROUND: Bipolar disorder is a common long-term mental health condition
characterised by episodes of mania or hypomania and depression resulting in
disability, early death, and high health and society costs. Public money funds
the National Institute of Healthcare and Clinical Excellence (NICE) to produce
clinical guidelines by systematically identifying the most up to date research
evidence and costing its main recommendations for healthcare organisations and
professionals to follow in England and Wales. Most governments, including those
of England and Wales, need to improve healthcare but at reduced cost. There is
evidence, particularly in bipolar disorder, that systematically following
clinical guidelines achieves these outcomes. DISCUSSION: NICE clinical
guidelines, including those regarding bipolar disorder, remain variably
implemented. They give clinicians and patients a non-prescriptive basis for
deciding their care. Despite the passing of the Health and Social Care Act in
2012 in England requiring all healthcare organisations to consider NICE clinical
guidelines in commissioning, delivering, and inspecting healthcare services,
healthcare organisations in the National Health Service may ignore them with
little accountability and few consequences. There is no mechanism to ensure that
healthcare professionals know or consider them. Barriers to their implementation
include the lack of political and professional leadership, the complexity of the
organisation of care and policy, mistrust of some processes and recommendations
of clinical guidelines, and a lack of a clear implementation model, strategy,
responsibility, or accountability. Mitigation to these barriers is presented
herein. SUMMARY: The variability, safety, and quality of healthcare might be
improved and its cost reduced if the implementation of NICE clinical guidelines,
such as those for bipolar disorder, were made the minimum starting point for
clinical decision-making and mandatory responsibilities of all healthcare
organisations and professionals.
PMID- 26420498
TI - Characterization of DNA variants in the human kinome in breast cancer.
AB - Kinases play a key role in cancer biology, and serve as potential clinically
useful targets for designing cancer therapies. We examined nucleic acid
variations in the human kinome and several known cancer-related genes in breast
cancer. DNA was extracted from fine needle biopsies of 73 primary breast cancers
and 19 metastatic lesions. Targeted sequencing of 518 kinases and 68 additional
cancer related genes was performed using the SOLiD sequencing platform. We
detected 1561 unique, non-synonymous variants in kinase genes in the 92 cases,
and 74 unique variants in 43 kinases that were predicted to have major functional
impact on the protein. Three kinase groups--CMGC, STE and TKL--showed greater
mutational load in metastatic compared to primary cancer samples, however, after
correction for multiple testing the difference was significant only for the TKL
group (P = 0.04). We also observed that a higher proportion of histologic grade 1
and 2 cases had high functional impact variants in the SCYL2 gene compared with
grade 3 cases. Our findings indicate that individual breast cancers harbor a
substantial number of potentially functionally important nucleotide variations in
kinase genes, most of which are present in unique combinations and include both
somatic and germline functional variants.
PMID- 26420499
TI - Ultrasound Elastography for Differentiating Benign from Malignant Thickened
Greater Omentum.
AB - OBJECTIVES: To investigate whether ultrasound elastography (UE) is an effective
non-invasive diagnostic procedure for evaluating benign and malignant thickened
greater omentum. METHODS: Ultrasound elastographic images from 118 patients who
underwent ultrasound-guided biopsy for thickened greater omentum from May 2012 to
October 2013 were retrospectively analysed. The results were compared with the
pathological findings from the biopsies, and evaluated by ROC curve analysis.
RESULTS: A total of 93.6% of the benign thickened greater omentum had elasticity
scoring of 1 or 2, whereas 93.0% of the malignant thickened greater omentum had
elasticity scoring of 3 or 4. The elasticity strain ratios for malignant
thickened greater omenta were higher than for benign thickened greater omenta
using muscle or fat yielded as reference tissue (P < 0.01). The optimal cut-off
point for elasticity strain ratios using fat as reference was 2.6. The
sensitivity, specificity, accuracy, and positive and negative predictive values
for determining elasticity strain ratios using fat as reference were 83.3%,
90.6%, 86.5%, 92.1%, and 80.6%, respectively, and for elasticity scoring were
95.2%, 96.9%, 95.9%, 97.6%, and 93.9%, respectively. CONCLUSIONS: UE using
elasticity scoring or elasticity strain ratios is an effective new non-invasive
method for differentiating benign from malignant thickened greater omentum. KEY
POINTS: * Elasticity score is an objective method for differentiating greater
omentum lesions. * Elasticity strain ratio is another method for differentiating
greater omentum lesions. * Fat tissue is better than abdominal wall muscle as
reference in elasticity imaging. * UE is a new effective, non-invasive method for
diagnosing omental diseases.
PMID- 26420501
TI - Junior doctors pledge to continue action unless Hunt improves offer.
PMID- 26420500
TI - T2 black lesions on routine knee MRI: differential considerations.
AB - The majority of abnormal findings or lesions on T2-weighted fast spin-echo (FSE)
magnetic resonance imaging (MRI) are hyperintense due to increased perfusion or
fluid content, such as infections, tumours or synovitis. Hypointense lesions on
T2-weighted images (both fat-suppressed and non-fat-suppressed) are less common
and can sometimes be overlooked. Such lesions have limited differential
diagnostic possibilities, and include vacuum phenomenon, loose body, tenosynovial
giant cell tumour, rheumatoid arthritis, haemochromatosis, gout, amyloid,
chondrocalcinosis, hydroxyapetite deposition disease, lipoma arborescens,
arthrofibrosis and iatrogenic lesions. These lesions often show characteristic
appearances and predilections in the knee. In this article, the authors describe
the MRI features of hypointense T2 lesions on routine knee MRI and outline a
systematic diagnostic approach towards their evaluation. Key Points * Hypointense
lesions on T2 images (T2 Dark Lesions) encompass limited diagnostic
possibilities. * T2 Dark lesions often show characteristic appearances and
predilections in the knee. * A systematic diagnostic approach will help
radiologists make the correct diagnosis.
PMID- 26420504
TI - Parameter Estimation for Gene Regulatory Networks from Microarray Data: Cold
Shock Response in Saccharomyces cerevisiae.
AB - We investigated the dynamics of a gene regulatory network controlling the cold
shock response in budding yeast, Saccharomyces cerevisiae. The medium-scale
network, derived from published genome-wide location data, consists of 21
transcription factors that regulate one another through 31 directed edges. The
expression levels of the individual transcription factors were modeled using mass
balance ordinary differential equations with a sigmoidal production function.
Each equation includes a production rate, a degradation rate, weights that denote
the magnitude and type of influence of the connected transcription factors
(activation or repression), and a threshold of expression. The inverse problem of
determining model parameters from observed data is our primary interest. We fit
the differential equation model to published microarray data using a penalized
nonlinear least squares approach. Model predictions fit the experimental data
well, within the 95% confidence interval. Tests of the model using randomized
initial guesses and model-generated data also lend confidence to the fit. The
results have revealed activation and repression relationships between the
transcription factors. Sensitivity analysis indicates that the model is most
sensitive to changes in the production rate parameters, weights, and thresholds
of Yap1, Rox1, and Yap6, which form a densely connected core in the network. The
modeling results newly suggest that Rap1, Fhl1, Msn4, Rph1, and Hsf1 play an
important role in regulating the early response to cold shock in yeast. Our
results demonstrate that estimation for a large number of parameters can be
successfully performed for nonlinear dynamic gene regulatory networks using
sparse, noisy microarray data.
PMID- 26420505
TI - Mathematical Model for MRSA Nasal Carriage.
AB - An interesting biological phenomenon that is a factor for the spread of
antibiotic-resistant strains, such as MRSA, is human nasal carriage. Here, we
evaluate several biological hypotheses for this problem in an effort to better
understand and narrow the scope of the dominant factors that allow these bacteria
to persist in otherwise healthy individuals. First, we set up and analyze a
simple PDE model created to generally mimic the interactions of the microbes and
nasal immune response. This includes looking at different types of diffusion and
chemotaxis terms as well as different boundary conditions. Then, using
sensitivity analysis, we walk through several biological hypotheses and compare
to the model's results looking for persistent infection scenarios indicated by
the model's bacteria component surviving over time.
PMID- 26420506
TI - Acute aortic dissection mimicking acute abdomen in a 14-year-old boy.
AB - Aortic dissection is extremely rare in children. Although it usually presents
with severe chest pain, atypical clinical presentations mimicking various
illnesses may cause misdiagnosis. In this report, the case of a 14-year-old boy
with symptoms suggestive of acute abdomen, which was finally diagnosed as aortic
dissection, is discussed.
PMID- 26420502
TI - Structural basis of glycan specificity in neonate-specific bovine-human
reassortant rotavirus.
AB - Strain-dependent variation of glycan recognition during initial cell attachment
of viruses is a critical determinant of host specificity, tissue-tropism and
zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in
infants and children, display significant genotype-dependent variations in glycan
recognition resulting from sequence alterations in the VP8* domain of the spike
protein VP4. The structural basis of this genotype-dependent glycan specificity,
particularly in human RVs, remains poorly understood. Here, from crystallographic
studies, we show how genotypic variations configure a novel binding site in the
VP8* of a neonate-specific bovine-human reassortant to uniquely recognize either
type I or type II precursor glycans, and to restrict type II glycan binding in
the bovine counterpart. Such a distinct glycan-binding site that allows
differential recognition of the precursor glycans, which are developmentally
regulated in the neonate gut and abundant in bovine and human milk provides a
basis for age-restricted tropism and zoonotic transmission of G10P[11]
rotaviruses.
PMID- 26420507
TI - Genetic dissection of the maize kernel development process via conditional QTL
mapping for three developing kernel-related traits in an immortalized F2
population.
AB - Kernel development is an important dynamic trait that determines the final grain
yield in maize. To dissect the genetic basis of maize kernel development process,
a conditional quantitative trait locus (QTL) analysis was conducted using an
immortalized F2 (IF2) population comprising 243 single crosses at two locations
over 2 years. Volume (KV) and density (KD) of dried developing kernels, together
with kernel weight (KW) at different developmental stages, were used to describe
dynamic changes during kernel development. Phenotypic analysis revealed that
final KW and KD were determined at DAP22 and KV at DAP29. Unconditional QTL
mapping for KW, KV and KD uncovered 97 QTLs at different kernel development
stages, of which qKW6b, qKW7a, qKW7b, qKW10b, qKW10c, qKV10a, qKV10b and qKV7
were identified under multiple kernel developmental stages and environments.
Among the 26 QTLs detected by conditional QTL mapping, conqKW7a, conqKV7a,
conqKV10a, conqKD2, conqKD7 and conqKD8a were conserved between the two mapping
methodologies. Furthermore, most of these QTLs were consistent with QTLs and
genes for kernel development/grain filling reported in previous studies. These
QTLs probably contain major genes associated with the kernel development process,
and can be used to improve grain yield and quality through marker-assisted
selection.
PMID- 26420509
TI - Mass transfer in electromembrane extraction--The link between theory and
experiments.
AB - Electromembrane extraction was introduced in 2006 as a totally new sample
preparation concept for the extraction of charged analytes present in aqueous
samples. Electromembrane extraction is based on electrokinetic migration of the
analytes through a supported liquid membrane and into a MUL-volume of acceptor
solution under the influence of an external electrical field. To date,
electromembrane extraction has mostly been used for the extraction of drug
substances, amino acids, and peptides from biological fluids, and for organic
micropollutants from environmental samples. Electromembrane extraction has
typically been combined with chromatography, mass spectrometry, and
electrophoresis for analyte separation and detection. At the moment, close to 125
research papers have been published with focus on electromembrane extraction.
Electromembrane extraction is a hybrid technique between electrophoresis and
liquid-liquid extraction, and the fundamental principles for mass transfer have
only partly been investigated. Thus, although there is great interest in
electromembrane extraction, the fundamental principle for mass transfer has to be
described in more detail for the scientific acceptance of the concept. This
review summarizes recent efforts to describe the fundamentals of mass transfer in
electromembrane extraction, and aim to give an up-to-date understanding of the
processes involved.
PMID- 26420508
TI - Denticle-embedded ampullary organs in a Cretaceous shark provide unique insight
into the evolution of elasmobranch electroreceptors.
AB - Here, we report a novel type of dermal denticle (or placoid scale), unknown among
both living and fossil chondrichthyan fishes, in a Cretaceous lamniform shark. By
their morphology and location, these dermal denticles, grouped into clusters in
the cephalic region, appear to have been directly associated with the
electrosensory ampullary system. These denticles have a relatively enlarged (~350
MUm in diameter), ornamented crown with a small (~100 MUm) asterisk- or cross
shaped central perforation connected to a multi-alveolate internal cavity. The
formation of such a complex structure can be explained by the annular coalescence
and fusion, around an ampullary vesicle, of several developmental units still at
papillary stage (i.e. before mineralization), leading to a single denticle
embedding an alveolar ampulla devoid of canal. This differs from larger typical
ampullae of Lorenzini with a well-developed canal opening in a pore of the skin
and may represent another adaptive response to low skin resistance. Since it has
been recently demonstrated that ampullary organs arise from lateral line placodes
in chondrichthyans, this highly specialized type of dermal denticle (most likely
non-deciduous) may be derived from the modified placoid scales covering the
superficial neuromasts (pit organs) of the mechanosensory lateral line system of
many modern sharks.
PMID- 26420510
TI - Changes in biochemical, hemodynamic, and dialysis adherence parameters in
hemodialysis patients during Ramadan.
AB - This paper aimed to study the effect of Ramadan fasting on biochemical and
clinical parameters and compliance for dialysis. A prospective multicenter
observational cross-sectional study comparing fasting with a non-fasting stable
adult hemodialysis patients for demographic and biochemical parameters,
compliance with dialysis, inter-dialytic weight gain, pre- and post-blood
pressure, and frequency of intradialytic hypotensive episodes was carried out.
Six hundred thirty-five patients, of whom 64.1% fasted, were studied. The fasters
were younger (53.3 +/- 16.2 vs. 58.4 +/- 16.1 years; P = 0.001) but had similar
duration on dialysis (P = 0.35). More fasters worked (22.0% vs. 14.6%; P = 0.001)
and missed dialysis sessions during Ramadan. No differences were noted between
groups in sex, diabetic status, or dialysis shift or day. There were no
differences in the pre- and post-dialysis blood pressure; serum potassium,
albumin or weight gain; diabetic status; sex; and dialysis shift time or days.
However, serum phosphorous was significantly higher in the fasting group (2.78 +/
1.8 vs. 2.45 +/- 1.6 mmol/L; P = 0.045). There were no intragroup differences in
any of the parameters studied when comparing the findings during Ramadan with
those in the month before Ramadan. Fasters were significantly younger and more
likely to be working, to miss dialysis sessions, and to have higher serum
phosphorous levels. No other differences were observed.
PMID- 26420511
TI - Flexible nanoporous tunable electrical double layer biosensors for sweat
diagnostics.
AB - An ultra-sensitive and highly specific electrical double layer (EDL) modulated
biosensor, using nanoporous flexible substrates for wearable diagnostics is
demonstrated with the detection of the stress biomarker cortisol in synthetic and
human sweat. Zinc oxide thin film was used as active region in contact with the
liquid i.e. synthetic and human sweat containing the biomolecules. Cortisol
detection in sweat was accomplished by measuring and quantifying impedance
changes due to modulation of the double layer capacitance within the electrical
double layer through the application of a low orthogonally directed alternating
current (AC) electric field. The EDL formed at the liquid-semiconductor interface
was amplified in the presence of the nanoporous flexible substrate allowing for
measuring the changes in the alternating current impedance signal due to the
antibody-hormone interactions at diagnostically relevant concentrations. High
sensitivity of detection of 1 pg/mL or 2.75 pmol cortisol in synthetic sweat and
1 ng/mL in human sweat is demonstrated with these novel biosensors. Specificity
in synthetic sweat was demonstrated using a cytokine IL-1beta. Cortisol detection
in human sweat was demonstrated over a concentration range from 10-200 ng/mL.
PMID- 26420512
TI - Metabolites and Changes in Antioxidant Activity of A-Type and B-Type
Proanthocyanidin Dimers after Incubation with Rat Intestinal Microbiota.
AB - Metabolism of B-type EC dimer, A-type EC dimer, A-type ECG dimer, and A-type EGCG
dimer was compared in vitro after incubation with rat intestinal microbiota for 0
24 h. A "dimeric" catabolite (m/z 815.6) was detected in four procyanthocyanidin
dimers. Although the early cleavage of the C4-C8 interflavan bond and the
reductive cleavage of the C-ring occurred in both B-type and A-type dimers, the
degradation routes of these two types of dimers might somewhat differ. A dimeric
catabolite C1 and more low molecular weight phenolic acids were detected in the
metabolites of A-type EC dimer, but not in B-type EC dimer. The antioxidant
capabilities of the A-type dimers were enhanced significantly after incubation
for 6 h, whereas the antioxidant capacity of B-type EC dimer decreased. The
results suggested that changes in antioxidant activity of procyanidin dimers
after bioconversion by rat intestinal microbiota were not only structure
dependent but also incubation condition dependent.
PMID- 26420513
TI - Pacific Populations, Metabolic Disease and 'Just-So Stories': A Critique of the
'Thrifty Genotype' Hypothesis in Oceania.
AB - Pacific populations have long been observed to suffer a high burden of metabolic
disease, including obesity, type 2 diabetes and gout. The 'Thrifty Genotype'
hypothesis has frequently been used to explain this high prevalence of disease.
Here, the 'Thrifty Genotype' hypothesis and the evolutionary background of
Pacific populations are examined. We question its relevance not only in the
Pacific region but more generally. Not only has the hypothesis not been
explicitly tested, but most archaeological and anthropological data from the
Pacific fundamentally do not support its application.
PMID- 26420515
TI - Near-Infrared Phosphorus-Substituted Rhodamine with Emission Wavelength above 700
nm for Bioimaging.
AB - Phosphorus has been successfully fused into a classic rhodamine framework, in
which it replaces the bridging oxygen atom to give a series of phosphorus
substituted rhodamines (PRs). Because of the electron-accepting properties of the
phosphorus moiety, which is due to effective sigma*-pi* interactions and
strengthened by the inductivity of phosphine oxide, PR exhibits extraordinary
long-wavelength fluorescence emission, elongating to the region above 700 nm,
with bathochromic shifts of 140 and 40 nm relative to rhodamine and silicon
substituted rhodamine, respectively. Other advantageous properties of the
rhodamine family, including high molar extinction coefficient, considerable
quantum efficiency, high water solubility, pH-independent emission, great
tolerance to photobleaching, and low cytotoxicity, stay intact in PR. Given these
excellent properties, PR is desirable for NIR-fluorescence imaging in vivo.
PMID- 26420516
TI - [Cancer pain management: Systematic review and critical appraisal of clinical
practice guidelines].
AB - OBJECTIVE: Although several clinical practice guidelines have been developed in
the last decades, cancer pain management is still deficient. The purpose of this
work was to carry out a comprehensive and systematic literature review of current
clinical practice guidelines on cancer pain management, and critically appraise
their methodology and content in order to evaluate their quality and validity to
cope with this public health issue. MATERIALS AND METHODS: A systematic review
was performed in the main databases, using English, French and Spanish as
languages, from 2008 to 2013. Reporting and methodological quality was rated with
the Appraisal of Guidelines, Research and Evaluation II (AGREE-II) tool,
including an inter-rater reliability analysis. Guideline recommendations were
extracted and classified into several categories and levels of evidence, aiming
to analyse guidelines variability and evidence-based content comprehensiveness.
RESULTS: Six guidelines were included. A wide variability was found in both
reporting and methodological quality of guidelines, as well as in the content and
the level of evidence of their recommendations. The Scottish Intercollegiate
Guidelines Network guideline was the best rated using AGREE-II, while the
Sociedad Espanola de Oncologia Medica guideline was the worst rated. The Ministry
of Health Malaysia guideline was the most comprehensive, and the Scottish
Intercollegiate Guidelines Network guideline was the second one. CONCLUSIONS: The
current guidelines on cancer pain management have limited quality and content. We
recommend Ministry of Health Malaysia and Scottish Intercollegiate Guidelines
Network guidelines, whilst Sociedad Espanola de Oncologia Medica guideline still
needs to improve.
PMID- 26420514
TI - Models and methods for in vitro testing of hepatic gap junctional communication.
AB - Inherent to their pivotal roles in controlling all aspects of the liver cell life
cycle, hepatocellular gap junctions are frequently disrupted upon impairment of
the homeostatic balance, as occurs during liver toxicity. Hepatic gap junctions,
which are mainly built up by connexin32, are specifically targeted by tumor
promoters and epigenetic carcinogens. This renders inhibition of gap junction
functionality a suitable indicator for the in vitro detection of nongenotoxic
hepatocarcinogenicity. The establishment of a reliable liver gap junction
inhibition assay for routine in vitro testing purposes requires a cellular system
in which gap junctions are expressed at an in vivo-like level as well as an
appropriate technique to probe gap junction activity. Both these models and
methods are discussed in the current paper, thereby focusing on connexin32-based
gap junctions.
PMID- 26420517
TI - Attribution-Based Nocebo Effects. Perceived Effects of a Placebo Pill and a Sham
Magnetic Field on Cognitive Performance and Somatic Symptoms.
AB - BACKGROUND: Negative non-specific (nocebo-like) effects of medications and
electromagnetic fields are often described as results of mistaken attribution.
PURPOSE: The current study aimed to find empirical evidence supporting this
theory. METHOD: Participants completed questionnaires assessing modern health
worries, health anxiety, and somatosensory amplification, were assigned to one of
three conditions (placebo pill with sedative information, sham magnetic field, or
control), and completed a 14-min vigilance task. Changes in physiological arousal
(heart rate, heart rate variability, and skin conductance) and reported symptoms
were also measured. Finally, causal attributions concerning cognitive performance
and reported symptoms were assessed. RESULTS: No increase in symptom reports and
physiological arousal was measured in the two intervention groups. A perceived
negative effect on cognitive performance was attributed to both sham conditions,
and attributions were connected to modern health worries. A proportion of
reported symptoms was ascribed to the placebo pill but not to the sham magnetic
field. Symptom attributions were not related to any assessed psychological
variables. CONCLUSIONS: An aroused physiological state is not necessary for the
automatic causal attribution process. Negative effects attributed to medication
and environmental factors can be regarded as unavoidable side effects of human
cognitive-emotional functioning; they might be alleviated, but cannot be
completely eradicated.
PMID- 26420519
TI - The emergency medicine research priority setting partnership.
PMID- 26420518
TI - How many preterm births in England are due to excision of the cervical
transformation zone? Nested case control study.
AB - BACKGROUND: Preterm births (as a proportion of all births) have been increasing
in many countries. There is growing evidence of increased risk of preterm birth
following excisional treatment of the cervix. We estimate the number of preterm
births attributable to excisional treatments with a length of 10 mm or more in
England. METHODS: Case-control study nested in a record linkage cohort of women
with a histological sample at 13 hospitals in England. We combined observed age
at first excisional treatment in our cohort with the weighted distribution of
excision length from the case-control study to estimate the length distribution
by age at first treatment among the cohort. The number of births after excision
for each 5-year age group was estimated using national fertility data; published
absolute risks of preterm (<37 gestational weeks) and very preterm birth (<32
weeks) were applied to these to estimate the number of preterm births per 100
women treated. Excess preterm births were estimated assuming all treatments were
small. The attributable risk of preterm birth following excisional treatment in
England was estimated. RESULTS: The majority of first excisional treatments at
colposcopy were small (47.5%) or medium (39.1%), 9.5% were large and 4.1% were
very large excisions. 4.0% of women treated before birth had more than one
excisional treatment. Thus based on our cohort of 10,711 treated women and the
length of treatment observed in the case control study we estimate an excess of
240 preterm births (including 57 very preterm) or 2.2 (including 0.5 very
preterm) per 100 women treated. At a population level (for England) we estimate
that 39,101 women aged 20-39 would be treated each year and that these treatments
will lead to an excess of 840 preterm births (including 196 very preterm) in
England each year. CONCLUSIONS: Assuming associations between preterm birth and
treatment for cervical disease are causal; we estimate that an excess 840 (2.5%)
preterm birth in England each year are due to excisional treatments of 10 mm or
more. Those that go on to become pregnant should be closely monitored during
antenatal period to reduce their risk of preterm birth.
PMID- 26420520
TI - Integrative review of nurse-led follow-up after discharge from the ICU.
AB - AIM AND OBJECTIVES: To analyse and synthesise the structure, content, types of
outcome variables and advantages of nurse-led follow-up of adult patients after
discharge from intensive care units. BACKGROUND: Follow-up service after
discharge from the intensive care unit has been suggested as a way of supporting
recovery of patients. Nevertheless, varieties exist in the understanding and
content of nurse-led follow-up. DESIGN: An integrative review of nurse-led follow
up inspired by the framework of Whittemore and Knafl. METHODS: An integrative
method merged with the recommendations of the PRISMA statement was used to
structure the review and findings. Online databases PubMed, CINAHL, ScienceDirect
and Scopus were searched from the years 2003-2014. The retrieved articles were
independently assessed by two reviewers. Critical appraisal was conducted using
check lists from Johanna Briggs Institute. Emerging patterns were validated by
all the authors throughout the entire process of analysis. RESULTS: Seventeen
papers were included. Three patterns of nurse-led follow-up were identified: (1)
Ward visits--in the immediate time after discharge from intensive care unit, (2)
Ward visits and appointment(s) to an intensive care unit follow-up clinic and (3)
follow-up visit to an intensive care unit and phone call(s) after discharge.
Content of short-term nurse-led follow-up (1) ranged from clinical assessment to
supporting patients in articulating their subjective health concerns. Long-term
nurse-led follow-up (2, 3) included appointments, phone call(s) or information on
where advice could be sought. Types of outcome variables were primarily
descriptive. There were strong implications for patients' satisfaction with nurse
led follow-up up to six months after discharge. CONCLUSION: Nurse-led follow-up
might promote patients' health and enable use of adequate resources. RELEVANCE TO
CLINICAL PRACTICE: The findings of this review could be used to design, and test,
future interventions and their implementation.
PMID- 26420521
TI - [History of incompability among medicinals of "Glycyrrhiza antagonistic to
Sargassum, Euphorbia Pekinensis, Kansui, and Genkwa" and its modern recognition].
AB - The allegation of "Glycyrrhiza antagonistic to Sargassum, Euphorbia Pekinensis,
Kansui, and Genkwa", being one of the hypotheses of "18 antagonisms" in TCM
pharmacology, is referring to the antagonistic action among the Radix et Rhizoma
Glycyrrhiza and Radix Euphorbiae Kansui, Radix Euphorbiae Pekinensis, Flos
Genkwa, and Sargassum when compounded together in a single recipe. By reviewing
its history concerted with modern knowledge, it can be found that the theory of
"seven emotions" was originated from Shennong's Classic of Materia Medica; while
the Variorum of the Classic of Materia Medica firstly and definitely records that
Radix et Rhizoma Glycyrrhizae is forbidden to be used with Radix Kansui, Flos
Genkwa, Radix Euphorbiae Pekinensis, Sargassum together in a single formula. It
was summarized into a Chinese poetic sentence as above-mentioned later. In the
works of later ages, including Chinese Pharmacopoeia, A Great Dictionary of
Chinese Materia Medica, and China's Herbology, etc., all enhance the
understanding of the prohibited combination of Radix et Rhizoma Glycyrrhizae and
its incompatible herbs. Nevertheless, there are discrepancies between the results
of modern experimental and clinical studies on this problem, which, needless to
say, should be resolved by further investigations.
PMID- 26420522
TI - [Evolution of the origin of strain of Shancigu (Rhizoma Pleionis)].
AB - Shancigu (Rhizome Pleionis) was first recorded in the Ben cao shiyi (Supplements
to Chinese Materia Medica). The source of the strain of this medicinal was
unclear because of its too simple description in the medical books in the Tang
and Song dynasties. Its original plant could be Cremastra appendiculata (D.Don)
Makino, Tulipa edulis (Miq.) Baker and so on. The original plant of Shanciguwas
Tulipaedulis since the Ming dynasty to the Republican period. The name of
"Guangcigu" began to appear in the Republican period because of the changes of
its processing method. The original plants evolved into Cremastra appendiculata,
Pleione bulbocodioides (Franch.) Rolfe and Pleione yunnanensis Rolfe, with Tulipa
edulisas the original plant of Guangcigu (Bulbus of Tulipasedulis). It is found
that only the Tulipaedulis is the unequivocal origin with the longest medicinal
history through sorting out of the original plants of Shancigu. Hence, it is
suggested that Tulipa edulis should be recovered as the original strain of
Shancigu.
PMID- 26420523
TI - [Medical application of the art of supplication before the Tang dynasty].
AB - Ample materials on diseases treated with supplication were seen on excavated
texts, medical works from ancient time, and religious works before the Tang
dynasty (including Tang dynasty). Since the breaking up of witchcraft from
medicine, there are still supplication applied in the treatment and prevention of
diseases, including those of internal medicine, external medicine, women's and
children's diseases, disease of the sense organs, and infections. There are dual
reasons for this phenomena, one being the diseases caused by spirit and ghostss;
and the other being certain effectiveness of this art on some diseases not cured
by other regular treatments, hence, its acceptance by secular people.
PMID- 26420524
TI - [The significance of drawing on experience of experimental study on Chinese
materia medica during the Republican period].
AB - During the period of the Republic of China, researches of experiments on Chinese
materia medica developed extensively with the scientific process of Chinese
medicine. Although the technology standard was relatively low and the reference
value, limited. The experiences, positive or negative, obtained at that time
still has reference significance to today's Chinese medicine scientific research.
The notion that traditional Chinese medical and scientific research be conducted
under the guidance of TCM theory; valuable experience contained in the ancient
literature of traditional Chinese medicine be collected; and the transformation
capacity of scientific research be elevated, has been accepted by modern TCM
professionals. If you go back to the history, it can be seen that this notion was
summarized through repeated practice during the critical moment of traditional
Chinese medicine, which should be emphasized and its understanding deepened at
any time.
PMID- 26420525
TI - [Crisis and vitality: new evaluation of the development of the Chinese Medicine
in the Republican period].
AB - By investigating the development process of the Republic of China with
pluralistic perspective, it can be seen that contemporary TCM was undergoing the
crises of theory, value, and survival, and rights which were a necessary steps
when entering a new historical stage. The mainstream of the development of TCM
during this period included fighting for its existence and self-strengthening,
which had gained five achievements, including prevention of the attempts of
abolishing TCM; involvement into the modern national political system;
inheritance of the integrity of academic system; the formation of embryonic shape
of new business, and the experience attained in the integration of Chinese and
Western Medicine. All these manifested its strong vitality, though it was
somewhat limited in its developmental level. It had laid down the basis for the
embryonic stage of developmental model of Chinese medicine after the twentieth
century.
PMID- 26420526
TI - [Exploration on the appraisal of Chinese medical lawsuit cases in the Republican
period].
AB - Since the doctor-patient relationship was increasingly tense during the
Republican period, Chinese medical lawsuit cases happened frequently due to
various sorts of dispute, and had become the focus in both medical and judiciary
fields. During this period, the Chinese medical professionals were highly
concerned about the rights of medical appraisal and opposed the appraisal made
only by western medical professionals alone. Through the establishment of various
sorts of appraisal units by professional community, academic groups, and medical
colleges, endeavor were made to improve the appraisal level of
professionalization and objectivity.
PMID- 26420527
TI - [New merge of knowledge of the acu-moxibustion academic in the Republican
period].
AB - During the republican period, western science and technology as well as western
medicine spread quickly in China, and inevitably had a profound influence on the
academic of acu-moxibustion. The confluence of Chinese and western medicine with
the scientification of acu-moxibustion had left an obvious mark on the academic
of acu-moxibustion. No matter whether the theory involves science of channels and
collaterals, acupoints and methods of needling and moxibustion or the improvement
of acu-moxibustion apparatus and new therpy methods, all carrying remarkable
characteristic of new merge of knowledge, and providing solid foundation and
valuable reference for the development of contemporary academic of acu
moxibustion.
PMID- 26420528
TI - [Development of external medicine and dermatology of TCM in the Republican
period].
AB - The inheritance of the theory in external medicine in the Republican period was
mainly derived from Wai ke zheng zong (Orthodox Manual of External Medicine) and
Yi zong jin jian (Golden Mirror of Medicine) and the sorting out of medical
plasters, pills, and powders from Wai ke shi san fang (Thirteen Recipes of
External Medicine). Zhang Shanlei's Yang ke gang yao (Guidelines for
Ulcerations), based on the five-year experience of Zhu's family, offers new
experience and ideas for syndrome differentiation; Ding Ganren's diagnosis for
external medicine is exquisite with many well known formulae prescribed by
himself; Monographs on leprosy and syphilis were published by famous physicians.
Departments of external medicine and anal diseases, and classes on external
medicine and dermatology and venereal diseases were set up in TCM schools in
Guangdong and Zhejiang provinces with teaching materials compiled. All these mark
the development of external medicine in modern age.
PMID- 26420529
TI - [Textual research on relationship between traditional Chinese medicine and
medical prescriptions in the Sanskrit formulary Bower Manuscript excavated in
Xinjiang].
AB - This paper introduces the Bower Manuscript in Sanskrit written on birch bark
excavated in Xinjiang, which was bought in Kuqa by a British India army
lieutenant Bower, hence its title. Then, it was researched, annotated, and
published in 7 volumes by a German British lieutenant and orientalist Honer. The
first three volumes are devoted to medical prescriptions. It is first verified
that its "Dazi Xiangye San" is the "Dujuan Dachen San" in Tibetan medicine. By
comparing it with other traditional medical systems, such as Chinese, Tibetan,
Mongolian, and Uyghur medical systems, we found that Bower Manuscript is closer
to Tibetan medicine and Mongolian medicine, while it has less relation with
Chinese medicine and Uyghur medicine. However, it also exerts some influence on
TCM.
PMID- 26420530
TI - [Philological structure of Dan xi shou jing (Danxi's Hand Mirror)].
AB - Zhu Danxi, one of the four Major Schools of the Jin-Yuan Dynasties, had a lot of
works circulated with its authorship in disarray. Part of the works were compiled
by his disciples, while others were by his self-taught followers based on prior
circulated Danxi's originals, plus some apocryphal so-called Danxi's works
circulated posthumously. When sorting out Danxi's Hand Mirror, we found that some
of its contents are closely related to Bei ji qian jin yao fang (Essential
Prescriptions Worth a Thousand Gold for Emergencies), Qian jin yi fang
(Supplements to Qian jin yao fang), Tai ping sheng hui fang (Peaceful Holy
Benevolent Prescriptions), Zhu jie shang han lun (Annotated Treatises of Cold
Pathogenic Disease), Shang han ming li lun (Elucidation of Cold Pathogenic
Disease), Ge zhi yu lun (Treatise of Inquiring the Properties of Things), either
by transcription or with an identical origin. By clearing their relationships, it
can provide assistance to the research of the philological structure of Danxi's
hand Mirror.
PMID- 26420531
TI - [Research on TCM periodical Tong su yi shi yue kan (Popular Medical Monthly), a
magazinepublished in Peking in the Republican period].
AB - The Popular Medical Monthly, a periodical inaugurated by the Aiyou Society in
October, 1919, was the earliest TCM periodical published in Peking, the goal of
which was to spread common medical knowledgeand hygienic ideas. It included
discussion, translation, investigation, random talk, record, and corresponding,
featuring popularizing medical and hygienic conception to the populace, upgrading
people's knowledge on seasonal epidemic disases, etc.
PMID- 26420532
TI - [An introduction to the Institute of History of Medicine in Medical School of
Johns Hopkins University].
AB - The Institute of History of Medicine in Medical School of Johns Hopkins
University is a well-known institute in the world. It includes the department of
history of medicine, a historic collection, a library of history of medicine and
an Editorial Board of the Bulletin of History of Medicine, embodying the tasks of
teaching, researching and publication. The faculty members are active and
outstanding in lots of fields of history of medicine. It leads the latest
research on history of medicine with extensive research scope and active academic
activities.
PMID- 26420533
TI - Sarcoid-like reaction mimicking vaginal cancer recurrence.
AB - A sarcoid-like reaction is a development of non-caseating granuloma in patients
with underlying malignancy and represents a false positive finding on positron
emission tomography/computed tomography (PET/CT). A sarcoid-like reaction is a
benign condition; therefore, differentiating a sarcoid-like reaction from cancer
recurrence is necessary. Only uterine and ovarian cancer related cases have been
reported in the gynecological field and to the best of our knowledge, this is the
first case of a sarcoid-like reaction in vaginal cancer. A 59-year-old vaginal
cancer patient received concurrent chemoradiotherapy and achieved complete
remission. Recurrence of vaginal cancer was suspected because of the elevation of
serum squamous cell carcinoma antigen level. PET/CT revealed abnormal uptake at
the bilateral mediastinal and hilar lymph nodes. A non-caseating granuloma was
detected from the biopsy of the swollen lymph nodes. No evidence of cancer
recurrence was observed. A sarcoid-like reaction should be considered when
evaluating PET/CT in cancer patients to prevent unnecessary treatments.
PMID- 26420534
TI - Graphene oxides and the angiogenic process.
PMID- 26420542
TI - Identification of STAT3 and STAT5 proteins in the rat suprachiasmatic nucleus and
the Day/Night difference in astrocytic STAT3 phosphorylation in response to
lipopolysaccharide.
AB - Signal transducers and activators of transcription (STAT) proteins regulate many
aspects of cellular physiology from growth and differentiations to immune
responses. Using immunohistochemistry, we show the daily rhythm of STAT3 protein
in the rat suprachiasmatic nucleus (SCN), with low but significant amplitude
peaking in the morning. We also reveal the strong expression of STAT5A in
astrocytes of the SCN and the STAT5B signal in nonastrocytic cells.
Administration of lipopolysaccharide (LPS) acutely induced phosphorylation of
STAT3 on Tyr705 during both the day and the night and induced phosphorylation on
Ser727 but only after the daytime application. The LPS-induced phospho-STAT3
(Tyr705) remained elevated for 24 hr after the daytime application but declined
within 8 hr when LPS was applied at night.
PMID- 26420544
TI - Proposal for a Domain Wall Nano-Oscillator driven by Non-uniform Spin Currents.
AB - We propose a new mechanism and a related device concept for a robust, magnetic
field tunable radio-frequency (rf) oscillator using the self oscillation of a
magnetic domain wall subject to a uniform static magnetic field and a spatially
non-uniform vertical dc spin current. The self oscillation of the domain wall is
created as it translates periodically between two unstable positions, one being
in the region where both the dc spin current and the magnetic field are present,
and the other, being where only the magnetic field is present. The vertical dc
spin current pushes it away from one unstable position while the magnetic field
pushes it away from the other. We show that such oscillations are stable under
noise and can exhibit a quality factor of over 1000. A domain wall under dynamic
translation, not only being a source for rich physics, is also a promising
candidate for advancements in nanoelectronics with the actively researched
racetrack memory architecture, digital and analog switching paradigms as
candidate examples. Devising a stable rf oscillator using a domain wall is hence
another step towards the realization of an all domain wall logic scheme.
PMID- 26420543
TI - Molecular detection and characterization of Babesia bovis, Babesia bigemina,
Theileria species and Anaplasma marginale isolated from cattle in Kenya.
AB - BACKGROUND: Infections with Babesia bovis, Babesia bigemina, Theileria species
and Anaplasma marginale are endemic in Kenya yet there is a lack of adequate
information on their genotypes. This study established the genetic diversities of
the above tick-borne hemoparasites infecting cattle in Kenya. METHODS: Nested PCR
and sequencing were used to determine the prevalence and genetic diversity of the
above parasites in 192 cattle blood samples collected from Ngong and Machakos
farms. B. bovis spherical body protein 4, B. bigemina rhoptry-associated protein
1a, A. marginale major surface protein 5, Theileria spp. 18S rRNA, T. parva p104
and T. orientalis major piroplasm surface protein were used as the marker genes.
RESULTS: B. bovis, B. bigemina, T. parva, T. velifera, T. taurotragi, T. mutans
and A. marginale were prevalent in both farms, whereas T. ovis, Theileria sp.
(buffalo) and T. orientalis were found only in Ngong farm. Co-infections were
observed in more than 50 % of positive samples in both farms. Babesia parasites
and A. marginale sequences were highly conserved while T. parva and T. orientalis
were polymorphic. Cattle-derived T. parva was detected in Machakos farm. However,
cattle and buffalo-derived Theileria were detected in Ngong farm suggesting
interactions between cattle and wild buffaloes. Generally, the pathogens detected
in Kenya were genetically related to the other African isolates but different
from the isolates in other continents. CONCLUSIONS: The current findings reaffirm
the endemicity and co-infection of cattle with tick-borne hemoparasites, and the
role of wildlife in pathogens transmission and population genetics in Kenya.
PMID- 26420545
TI - Structural insights into the loss of catalytic competence in pectate lyase
activity at low pH.
AB - Pectate lyase, a family 1 polysaccharide lyase, catalyses cleavage of the alpha
1,4 linkage of the polysaccharide homogalacturonan via an anti beta-elimination
reaction. In the Michaelis complex two calcium ions bind between the C6
carboxylate of the d-galacturonate residue and enzyme aspartates at the active
centre (+1 subsite), they withdraw electrons acidifying the C5 proton
facilitating its abstraction by the catalytic arginine. Here we show that
activity is lost at low pH because protonation of aspartates results in the loss
of the two catalytic calcium-ions causing a profound failure to correctly
organise the Michaelis complex.
PMID- 26420547
TI - Hypopituitarism in Neurocritical Patients: A Case Report.
AB - BACKGROUND: Besides changes in pituitary hormones secretion observed during the
acute phase of stroke as an adaptive response to injury or an effect of drugs, a
true hypopituitarism due to ischemic and/or hemorrhagic damage at the
hypothalamus and/or pituitary gland can develop after a stroke. CASE REPORT: We
report a case of a 72-year-old woman showing clinical signs and laboratory data
suggesting a secondary adrenal insufficiency following a recent acute brain
ischemia. Cortisone therapy significantly improved this pituitary dysfunction.
CONCLUSIONS: Clinicians must pay attention to the hypothalamic-pituitary axis in
neurocritical patients because hormonal replacement therapy may be life-saving.
PMID- 26420546
TI - Decreased Serotonin Levels and Serotonin-Mediated Osteoblastic Inhibitory
Signaling in Patients With Ankylosing Spondylitis.
AB - Evidence suggests that serotonin is an inhibitor of bone formation. We aimed to
assess: 1) serum serotonin levels in patients with ankylosing spondylitis (AS), a
prototype bone-forming disease, compared with patients with rheumatoid arthritis
(RA) and healthy subjects; 2) the effect(s) of TNFalpha blockers on serum
serotonin levels in patients with AS and RA; and 3) the effect(s) of serum of AS
patients on serotonin signaling. Serum serotonin levels were measured in 47
patients with AS, 28 patients with RA, and 40 healthy subjects by
radioimmunoassay; t test was used to assess differences between groups. The
effect of serum on serotonin signaling was assessed using the human osteoblastic
cell line Saos2, evaluating levels of phospho-CREB by Western immunoblots.
Serotonin serum levels were significantly lower in patients with AS compared with
healthy subjects (mean +/- SEM ng/mL 122.9 +/- 11.6 versus 177.4 +/- 24.58, p =
0.038) and patients with RA (mean +/- SEM ng/mL 244.8 +/- 37.5, p = 0.0004).
Patients with AS receiving TNFalpha blockers had significantly lower serotonin
levels compared with patients with AS not on such treatment (mean +/- SEM ng/mL
95.8 +/- 14.9 versus 149.2 +/- 16.0, p = 0.019). Serotonin serum levels were
inversely correlated with pCREB induction in osteoblast-like Saos-2 cells.
Serotonin levels are low in patients with AS and decrease even further during
anti-TNFalpha treatment. Differences in serotonin levels are shown to have a
functional impact on osteoblast-like Saos-2 cells. Therefore, serotonin may be
involved in new bone formation in AS.
PMID- 26420548
TI - Evaluation of Thyroid Hormone Status in Children with Steroid Resistant Nephrotic
Syndrome: A North India Study.
AB - BACKGROUND: Steroid resistant nephrotic syndrome (SRNS) has a chronic and
progressive course. Limited data is available evaluating thyroid function
parameters in SRNS patients. The aim of the present study was to evaluate the
thyroid hormone status in Indian children with SRNS. MATERIALS & METHODS: The
present cross-sectional study included 50 patients aged 1-12 years with SRNS. As
per Up:Uc ratio divided into three groups: Group A) 16 patients of SRNS in
complete remission Group B) 14 patients of SRNS in partial remission Group C) 20
patients of SRNS in relapse. Serum levels of FT3, FT4 and TSH were measured in
all. RESULTS: 20% of the children (n=10) with SRNS had hypothyroidism (7
subclinical hypothyroidism and 3 with overt hypothyroidism). One child was found
to be in complete remission, 4 in partial remission and 5 in relapse phase. TSH
levels were found to be significantly elevated in children with relapse (p =
0.042). Serum albumin showed a significant negative correlation with Up:Uc ratio
( p < 0.0001) whereas total cholesterol showed a significant positive correlation
(p < 0.001). On correlating TSH level with Up:Uc ratio a significant positive
correlation ( p = 0.0098) was observed. CONCLUSION: Subclinical hypothyroidism in
SRNS is temporary and may improve with remission. However prolonged proteinuria
in SRNS patients may lead to progressive damage of the renal tubules and impaired
absorption of Low Molecular Weight (LMW) proteins which may further exhaust the
thyroid reserve and lead to overt hypothyroidism. Therefore thyroid examination
should be routinely advocated in these children.
PMID- 26420550
TI - Using the Program Evaluation Committee as a Dynamic Vehicle for Improvement in
Psychiatry Training.
PMID- 26420551
TI - The promise of open innovation in drug discovery: an industry perspective.
PMID- 26420552
TI - Adhesive hydrophobicity of Cu2O nano-columnar arrays induced by nitrogen ion
irradiation.
AB - Low energy nitrogen ions are used in this work to manipulate wetting properties
of the surface of the array of Cu2O nano-columns, which yields remarkable
results. The nano-columnar thin films were grown on a highly conductive silicon
surface by a sputter deposition technique. The films were irradiated at two
different fluences of 5 * 10(15) and 1 * 10(16) ions per cm(2), respectively.
With increasing fluence the shape of column tip changes, columns are bent and
porous channels between columns are clogged up. While the surface of the pristine
sample is hydrophilic, the irradiated surface turns into hydrophobic but having
adhesion properties. We have analysed the structural and chemical properties of
the surface in detail to understand the initial and modified wetting properties.
Furthermore, the temporal evolutions of different droplet parameters are
investigated to realize the interactions between the water droplet, the sample
surface and the atmosphere. We envisage that such modified surfaces can be
beneficial for transport of a small volume of liquids with minimum loss and
spectroscopic studies, where a small amount of water droplet is available for
measurements.
PMID- 26420553
TI - Evaluation of Social Media Utilization by Latino Adolescents: Implications for
Mobile Health Interventions.
AB - BACKGROUND: Trends in social media use, including sending/receiving short message
service (SMS) and social networking, are constantly changing, yet little is known
about adolescent's utilization and behaviors. This longitudinal study examines
social media utilization among Latino youths, and differences by sex and
acculturation. OBJECTIVES: The purpose of this study was to examine Latino
adolescents' social media utilization and behavior over a 16-month period, and to
assess whether changes in use differed by sex and acculturation. METHODS: This
study included 555 Latino youths aged 13-19 who completed baseline and 16-month
follow-up surveys. Prevalence of social media utilization and frequency, by sex
and acculturation categories, was examined using generalized estimating
equations. RESULTS: Women are more likely to use SMS, but men are significantly
more likely to SMS a girl/boyfriend (P=.03). The use of Internet by men and women
to research health information increased over time. Facebook use declined over
time (P<.001), whereas use of YouTube (P=.03) and Instagram (P<.001) increased,
especially among women and more US acculturated youths. CONCLUSION: Social media
is ubiquitous in Latino adolescents' lives and may be a powerful mode for public
health intervention delivery.
PMID- 26420555
TI - Overpaying morbidity adjusters in risk equalization models.
AB - Most competitive social health insurance markets include risk equalization to
compensate insurers for predictable variation in healthcare expenses. Empirical
literature shows that even the most sophisticated risk equalization models-with
advanced morbidity adjusters-substantially undercompensate insurers for selected
groups of high-risk individuals. In the presence of premium regulation, these
undercompensations confront consumers and insurers with incentives for risk
selection. An important reason for the undercompensations is that not all
information with predictive value regarding healthcare expenses is appropriate
for use as a morbidity adjuster. To reduce incentives for selection regarding
specific groups we propose overpaying morbidity adjusters that are already
included in the risk equalization model. This paper illustrates the idea of
overpaying by merging data on morbidity adjusters and healthcare expenses with
health survey information, and derives three preconditions for meaningful
application. Given these preconditions, we think overpaying may be particularly
useful for pharmacy-based cost groups.
PMID- 26420556
TI - Reduction of Eu(3+) due to a change of the topological structure of the BO3 unit
in borate glass.
AB - Adjusting and controlling an ion's chemical state has always been a focus of
researchers' attention. Herein, an intense long-lasting phosphorescence of Eu(2+)
is obtained without any sacrificial reductant. The remarkable self-reducing
process and the unique luminescence properties stem from a variation of the
topological structure of the BO3 triangle.
PMID- 26420554
TI - Mode of allocation and social demographic factors correlate with impaired quality
of life after liver transplantation.
AB - BACKGROUND: Health-related Quality of life (HRQoL) is a major goal of clinical
management after liver transplantation (LTx). There is still disagreement on the
effects of social-demographic factors and changes in the allocation system on
HRQoL. The aim of this study was to evaluate the impact of social-demographic
factors, mode of organ-allocation, waiting time and hepatocellular carcinoma
(HCC) on HRQoL after LTx. METHODS: HRQoL was assessed using the EORTC-QLQ-C30
questionnaire, which was sent to 238 recipients. Investigated parameters included
age, sex, distance to transplant center, follow-up at hospital, size of hometown,
highest education, marital status, having children, background liver disease,
waiting time, mode of allocation, HCC, hospitalization after LTx and diagnosis of
malignancy after LTx. All evaluated parameters were entered into multivariate
linear regression analysis. RESULTS: Completed questionnaire were returned by 73%
of the recipients. After LTx, the HRQoL-function scales increased over time. Age,
marital status, highest education, completed professional training, working
status, job position, duration of waiting time to LTx, distance to transplant
center, place offollow, HU-statuts, mode of organ allocation and duration of
hospitalization were associated with significantly worse function- and
significantly lower symptom scales. HCC as a primary disease did not affect
HRQoL. CONCLUSIONS: Low HRQoL correlated significantly with MELD-based organ
allocation, more than 28-day hospitalization, divorced status, lower education-
and non-working status, higher distance to transplant center, follow up at
transplant center, HU-status, shorter waiting time to LTx and younger age.
Improvement of HRQoL after LTx may require clinical management of pain,
psychotherapy and financial support.
PMID- 26420562
TI - Structure and energetics of graphene oxide isomers: ab initio thermodynamic
analysis.
AB - Graphene oxide (GO) holds significant promise for electronic devices and
nanocomposite materials. A number of models were proposed for the GO structure,
combining carboxyl, hydroxyl, carbonyl and epoxide groups at different locations.
The complexity and variety of GO isomers, whose thermodynamic stability and
formation kinetics depend on the applied conditions, make determination of the GO
structure with atomistic precision challenging. We report high level theoretical
investigation of multiple molecular configurations, which are anticipated in GO.
We conclude that all oxygen containing groups at the GO surface are
thermodynamically permitted, whereas the 'edge' positions are systematically more
favorable than the 'center' and 'side' positions. We discuss a potentially novel
type of chemical bond or bonding reinforcement in GO, which consists of a
covalent bond and a strong electrostatic contribution from a polarized graphene
plane. We observe and analyze significant modifications of the graphene geometry
and electronic structure upon oxidation. The reported thermodynamic data guide
experiments aimed at deciphering the GO chemical composition and structure, and
form the basis for predicting GO properties required for nano-technological
applications.
PMID- 26420557
TI - Transcriptional responses and flavor volatiles biosynthesis in methyl jasmonate
treated tea leaves.
AB - BACKGROUND: Tea (Camellia sinensis) has long been consumed worldwide for its
amazing flavor and aroma. Methyl jasmonate (MeJA), which acts as an effective
elicitor among the plant kingdom, could mostly improve the quality of tea aroma
by promoting flavor volatiles in tea leaves. Although a variety of volatile
secondary metabolites that contribute to aroma quality have been identified, our
understanding of the biosynthetic pathways of these compounds has remained
largely incomplete. Therefore, information aboaut the transcriptome of tea leaves
and, specifically, details of any changes in gene expression in response to MeJA,
is required for a better understanding of the biological mechanisms of MeJA
mediated volatiles biosynthesis. Moreover, MeJA treatment could exaggerate the
responses of secondary metabolites and some gene expression which offer a better
chance to figure out the mechanism. RESULTS: The results of two-dimensional gas
chromatograph mass-spectrometry showed that the terpenoids content in MeJA
treated tea leaves increased, especially linalool, geraniol, and phenylethyl
alcohol. More importantly, we carried out RNA-seq to identify the differentially
expressed genes (DEGs) related to volatiles biosynthesis pathways induced by MeJA
treatment (0 h, 12 h, 24 h and 48 h) in tea leaves. We identified 19245, 18614,
11890 DEGs respectively in the MeJA_12h, MeJA_24 h and MeJA_48 h samples. The
alpha-Lenolenic acid degradation pathway was firstly responded resulting in
activating the JA-pathway inner tea leaves, and the MEP/DOXP pathway
significantly exaggerated. Notably, the expression level of jasmonate O
methyltransferase, which is associated with the central JA biosynthesis pathway,
was increased by 7.52-fold in MeJA_24 h tea leaves. Moreover, the genes related
to the terpenoid backbone biosynthesis pathway showed different expression
patterns compared with the untreated leaves. The expression levels of 1-deoxy-D
xylulose-phosphate synthase (DXS), all-trans-nonaprenyl-diphosphate synthase,
geranylgeranyl reductase, geranylgeranyl diphosphate synthase (type II),
hydroxymethylglutaryl-CoA reductase and 4-hydroxy-3-methylbut-2-enyl diphosphate
reductase increased by approximately 2-4-fold. CONCLUSIONS: The results of two
dimension gas-chromatography mass-spectrometry analysis suggested that exogenous
application of MeJA could induce the levels of volatile components in tea leaves,
especially the geraniol, linalool and its oxides. Moreover, the transcriptome
analysis showed increased expression of genes in alpha-Lenolenic acid degradation
pathway which produced massive jasmonic acid and quickly activated holistic JA
pathway inner tea leaves, also the terpenoid backbones biosynthesis pathway was
significantly affected after MeJA treatment. In general, MeJA could greatly
activate secondary metabolism pathways, especially volatiles. The results will
deeply increase our understanding of the volatile metabolites biosynthesis
pathways of tea leaves in response to MeJA.
PMID- 26420563
TI - Giant sialolith of submandibular gland duct treated by excision and ductal
repair: a case report.
PMID- 26420565
TI - Targeting tumor glycolysis by a mitotropic agent.
AB - Metabolic reprogramming is one of the hallmarks of cancer. Altered metabolism in
cancer cells is exemplified by enhanced glucose utilization, a biochemical
signature that is clinically exploited for cancer diagnosis using positron
emission tomography and computed tomography imaging. Accordingly, disrupting the
glucose metabolism of cancer cells has been contemplated as a potential
therapeutic strategy against cancer. Experimental evidences indicate that
targeting glucose metabolism by inhibition of glycolysis or oxidative
phosphorylation promotes anticancer effects. Yet, successful clinical translation
of antimetabolites or energy blockers to treat cancer remains a challenge,
primarily due to lack of efficacy and/or systemic toxicity. Recently, using
nanotechnology, Marrache and Dhar have documented the feasibility of delivering a
glycolytic inhibitor through triphenylphosphonium (TPP), a mitotropic agent that
selectively targets mitochondria based on membrane potential. Furthermore, by
utilizing gold nanoparticles the investigators also demonstrated the potential
for simultaneous induction of photothermal therapy, thus facilitating an
additional line of attack on cancer cells. The report establishes that specific
inhibition of tumor glycolysis is achievable through TPP-dependent selective
targeting of cancer cells. This nanotechnological approach involving TPP-guided
selective delivery of an antiglycolytic agent complemented with photothermal
therapy provides a new window of opportunity for effective and specific targeting
of tumor glycolysis.
PMID- 26420564
TI - Complications of otitis media - a potentially lethal problem still present.
AB - INTRODUCTION: It is an erroneous but commonly held belief that intracranial
complications (ICCs) of chronic and acute otitis media (COM and AOM) are past
diseases or from developing countries. These problems remain, despite
improvements in antibiotic care. OBJECTIVE: This paper analyzes the occurrence
and clinical characteristics and course of the main ICCs of otitis media (OM).
METHODS: Retrospective cohort study of 51 patients with ICCs from OM, drawn from
all patients presenting with OM to the emergency room of a large inner-city
tertiary care hospital over a 22-year period. RESULTS: 80% of cases were
secondary to COM of which the incidence of ICC was 0.8%; 20% were due to AOM. The
death occurrence was 7.8%, hearing loss in 90%, and permanent neurological
sequelae in 29%. Patients were 61% male. In the majority, onset of ear disease
had occurred during childhood. Delay of diagnosis of both the initial infection
as well as the secondary ICC was significant. ICCs included brain abscess and
meningitis in 78%, and lateral sinus thrombosis, empyema and otitic hydrocephalus
in 13%, 8% and 1% of cases, respectively. Twenty-seven neurosurgical procedures
and 43 otologic surgery procedures were performed. Two patients were too ill for
surgical intervention. CONCLUSION: ICCs of OM, although uncommon, still occur.
These cases require expensive, complex and long-term inpatient treatment and
frequently result in hearing loss, neurological sequelae and mortality. It is
important to be aware of this potentiality in children with COM, especially, and
maintain a high index of suspicion in order to refer for otologic specialty care
before such complications occur.
PMID- 26420566
TI - Kinetic Insights into the Elongation Reaction of Actin Filaments as a Function of
Temperature, Pressure, and Macromolecular Crowding.
AB - Actin polymerization is an essential process in eukaryotic cells that provides a
driving force for motility and mechanical resistance for cell shape. By using
preformed gelsolin-actin nuclei and applying stopped-flow methodology, we
quantitatively studied the elongation kinetics of actin filaments as a function
of temperature and pressure in the presence of synthetic and protein crowding
agents. We show that the association of actin monomers to the pointed end of
double-stranded helical actin filaments (F-actin) proceeds via a transition state
that requires an activation energy of 56 kJ mol(-1) for conformational and
hydration rearrangements, but exhibits a negligible activation volume, pointing
to a compact transition state that is devoid of packing defects. Macromolecular
crowding causes acceleration of the F-actin elongation rate and counteracts the
deteriorating effect of pressure. The results shed new light on the combined
effect of these parameters on the polymerization process of actin, and help us
understand the temperature and pressure sensitivity of actin polymerization under
extreme conditions.
PMID- 26420567
TI - Reliability and validity of CDAI and SDAI indices in comparison to DAS-28 index
in Moroccan patients with rheumatoid arthritis.
AB - BACKGROUND: Clinical disease activity index (CDAI) and simplified disease
activity index (SDAI) are useful tools for the evaluation of disease activity in
patients with rheumatoid arthritis (RA), but have not been comparatively
validated in Moroccan population. Therefore, this study was designed to assess
validity and reliability of CDAI and SDAI in comparison to disease activity score
28 joints (DAS-28) in Moroccan patients with RA. METHODS: Patients with RA were
included in a cross-sectional study. Patient characteristics and RA were
collected. The disease activity was assessed by DAS-28, CDAI and SDAI. Patients
were splitted into groups of remission, low, moderate and high activity on the
basis of predefined cut-offs for DAS-28, CDAI, and SDAI. A Spearman correlation
between composite indexes and inter-group comparison of the indexes were
performed. Using DAS-28 as a gold standard, the Receiver operator characteristic
(ROC) curve was used to assess the performance of a screening test at different
levels. RESULTS: The study was conducted with 103 patients of female predominance
(87.4%). Mean age was 49.7 +/- 11.4 years. Median disease duration was in the
order of 8 years [3-14]. There was an excellent correlation between DAS-28 and
CDAI (r = 0.95, p <0.001), CDAI and SDAI (r = 0.90, p <0.001), and DAS-28 and
SDAI (r = 0.92, p <0.001). There was a good inter-rater alignment between the DAS
28 and CDAI (Weighted kappa =0.743) and there was a moderate inter-rater
alignment between the DAS-28 and SDAI (Weighted kappa =0.60), and also between
the SDAI and CDAI (Weighted kappa = 0.589). There was no statistically
significant difference between AUROC of CDAI and SDAI as both were performed
equally well. DISCUSSION: This study is the first Moroccan case study to compare
the performance of both CDAI and SDAI in evaluation of disease activity in
patients with RA. Our study showed that there was a direct and excellent
correlation between DAS-28 and CDAI, and SDAI and DAS-28. CONCLUSION: Our study
shows a strong positive correlation between DAS-28, CDAI and SDAI. The cut-off
values for CDAI and SDAI used in western literature can be used with minor
modifications in Moroccan scenario.
PMID- 26420568
TI - Work participation in adults with Marfan syndrome: Demographic characteristics,
MFS related health symptoms, chronic pain, and fatigue.
AB - Marfan syndrome (MFS) is a severe autosomal dominant connective tissue disorder
that might influence peoples work ability. This cross sectional study aims to
investigate work participation in adults with verified MFS diagnosis and to
explore how the health related consequences of MFS and other factors might
influence work participation. The prevalence of health problems in young adults
compared to older adults with MFS was examined in association to work
participation. A postal questionnaire including questions about work
participation, demographic characteristics, MFS related health problems, chronic
pain, and fatigue was sent to 117 adults with verified MFS (Ghent 1), and 62%
answered. Fifty-nine percent were employed or students, significantly lower work
participation than the General Norwegian Population (GNP), but higher than the
Norwegian population of people with disability. Most young adults worked full
time despite extensive health problems, but the average age for leaving work was
low. Few had received any work adaptations prior to retiring from work. In
multiple logistic regression analysis, only age, lower educational level and
severe fatigue were significantly associated with low work participation; not MFS
related health problems or chronic pain. Fatigue appears to be the most
challenging health problem to deal with in work, but the covariance is complex.
Focus on vocational guidance early in life, more appropriate work adaptations,
and psychosocial support might improve the possibility for sustaining in work for
adults with MFS. More research about work challenges in adults with MFS is
needed.
PMID- 26420569
TI - Identification of a major radiometabolite of [11C]PBB3.
AB - INTRODUCTION: [(11)C]PBB3 is a clinically used positron emission tomography (PET)
probe for in vivo imaging of tau pathology in the brain. Our previous study
showed that [(11)C]PBB3 was rapidly decomposed to a polar radiometabolite in the
plasma of mice. For the pharmacokinetic evaluation of [(11)C]PBB3 it is important
to elucidate the characteristics of radiometabolites. In this study, we
identified the chemical structure of a major radiometabolite of [(11)C]PBB3 and
proposed the metabolic pathway of [(11)C]PBB3. METHODS: Carrier-added [(11)C]PBB3
was injected into a mouse for in vivo metabolite analysis. The chemical structure
of a major radiometabolite was identified using LC-MS. Mouse and human liver
microsomes and liver S9 samples were incubated with [(11)C]PBB3 in vitro. In
silico prediction software was used to assist in the determination of the
metabolite and metabolic pathway of [(11)C]PBB3. RESULTS: In vivo analysis showed
that the molecular weight of a major radiometabolite of [(11)C]PBB3, which was
called as [(11)C]M2, was m/z 390 [M+H(+)]. In vitro analysis assisted by in
silico prediction showed that [(11)C]M2, which was not generated by cytochrome
P450 enzymes (CYPs), was generated by sulfated conjugation mediated by a
sulfotransferase. CONCLUSION: The major radiometabolite, [(11)C]M2, was
identified as a sulfated conjugate of [(11)C]PBB3. [(11)C]PBB3 was metabolized
mainly by a sulfotransferase and subsidiarily by CYPs.
PMID- 26420570
TI - Drug-induced hypersensitivity syndrome by liposomal amphotericin-B: a case
report.
AB - BACKGROUND: Liposomal amphotericin-B (Ambisome((r))) is widely used antifungal
drug for treatments of invasive fungal infections. The use of liposomal
amphotericin-B is increasing in medical setting because of its tolerability and
potent antifungal activity. CASE PRESENTATION: In a case of a 76 year-old
Japanese female was admitted with subarachnoid hemorrhage, the ethnicity of the
patient is Asian, we experienced that liposomal amphotericin-B was the culprit
drug for Drug-induced hypersensitivity syndrome, also known as drug rash with
eosinophilia and systemic symptoms in view of a clear temporal relationship
between liposomal amphotericin-B administration and the onset of symptoms, the
remission of the symptomatological pattern after liposomal amphotericin-B
withdrawal. CONCLUSION: The present case report shows that prolonged liposomal
amphotericin-B treatment can be associated with drug rash with eosinophilia and
systemic symptoms. We recommend careful monitoring of neutrophil counts in a
prolonged treatment course with liposomal amphotericin-B.
PMID- 26420572
TI - Effects of inorganic acids and divalent hydrated metal cations (Mg(2+), Ca(2+),
Co(2+), Ni(2+)) on gamma-AlOOH sol-gel process.
AB - In-depth understanding of the sol-gel process plays an essential role in guiding
the preparation of new materials. Herein, the effects of different inorganic
acids (HCl, HNO3 and H2SO4) and divalent hydrated metal cations (Mg(2+), Ca(2+),
Co(2+), Ni(2+)) on gamma-AlOOH sol-gel process were studied based on experiments
and density functional theory (DFT) calculations. In these experiments, the sol
originating from the gamma-AlOOH suspension was formed only with the addition of
HCl and HNO3, but not with H2SO4. Furthermore, the DFT calculations showed that
the strong adsorption of HSO4(-) on the surface of the gamma-AlOOH particles, and
the hydrogen in HSO4(-) pointing towards the solvent lead to an unstable
configuration of electric double layer (EDL). In the experiment, the gelation
time sequence of gamma-AlOOH sol obtained by adding metal ions changed when the
ionic strength was equal to or greater than 0.198 mol kg(-1). The DFT
calculations demonstrated that the adsorption energy of hydrated metal ions on
the gamma-AlOOH surface can actually make a difference in the sol-gel process.
PMID- 26420571
TI - Protocol for a systematic review on the effect of demand generation interventions
on uptake and use of modern contraceptives in LMIC.
AB - BACKGROUND: Despite a global increase in contraception use, its prevalence
remains low in low- and middle-income countries. One strategy to improve uptake
and use of contraception, as an essential complement to policies and supply-side
interventions, is demand generation. Demand generation interventions have
reportedly produced positive effects on uptake and use of family planning
services, but the evidence base remains poorly documented. To reduce this
knowledge gap, we will conduct a systematic review on the impact of demand
generation interventions on the use of modern contraception. The objectives of
the review will be as follows: (1) to synthesize evidence on the impacts and
costs of family planning demand generation interventions and on their
effectiveness in improving modern contraceptive use and (2) to identify the
indicators used to assess effectiveness, cost-effectiveness, and impacts of
demand generation interventions. METHODS/DESIGN: We will systematically review
the public health and health promotion literature in several databases (e.g.,
CINAHL, Medline, EMBASE) as well as gray literature. We will select articles from
1970 to 2015, in French and in English. The review will include studies that
assess the impact of family planning programs or interventions on changes in
contraception use. The studied interventions will be those with a demand
generation component, even if a supply component is implemented. Two members of
the team will independently search, screen, extract data, and assess the quality
of the studies selected. Different tools will be used to assess the quality of
the studies depending on the study design. If appropriate, a meta-analysis will
be conducted. The analysis will involve comparing odd ratios (OR) DISCUSSION: The
systematic review results will be disseminated to United Nations Population Fund
program countries and will contribute to the development of a guidance document
and programmatic tools for planning, implementing, and evaluating demand
generation interventions in family planning. Improving the effectiveness of
family planning programs is critical for empowering women and adolescent girls,
improving human capital, reducing dependency ratios, reducing maternal and child
mortality, and achieving demographic dividends in low- and middle-income
countries. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered in
PROSPERO (CRD 42015017549).
PMID- 26420573
TI - The effect of brain size evolution on feeding propensity, digestive efficiency,
and juvenile growth.
AB - One key hypothesis in the study of brain size evolution is the expensive tissue
hypothesis; the idea that increased investment into the brain should be
compensated by decreased investment into other costly organs, for instance the
gut. Although the hypothesis is supported by both comparative and experimental
evidence, little is known about the potential changes in energetic requirements
or digestive traits following such evolutionary shifts in brain and gut size.
Organisms may meet the greater metabolic requirements of larger brains despite
smaller guts via increased food intake or better digestion. But increased
investment in the brain may also hamper somatic growth. To test these hypotheses
we here used guppy (Poecilia reticulata) brain size selection lines with a
pronounced negative association between brain and gut size and investigated
feeding propensity, digestive efficiency (DE), and juvenile growth rate. We did
not find any difference in feeding propensity or DE between large- and small
brained individuals. Instead, we found that large-brained females had slower
growth during the first 10 weeks after birth. Our study provides experimental
support that investment into larger brains at the expense of gut tissue carries
costs that are not necessarily compensated by a more efficient digestive system.
PMID- 26420576
TI - Propane sigma-Complexes on PdO(101): Spectroscopic Evidence of the Selective
Coordination and Activation of Primary C-H Bonds.
AB - Achieving selective C-H bond cleavage is critical for developing catalytic
processes that transform small alkanes to value-added products. The present study
clarifies the molecular-level origin for an exceptionally strong preference for
propane to dissociate on the crystalline PdO(101) surface via primary C-H bond
cleavage. Using reflection absorption infrared spectroscopy (RAIRS) and density
functional theory (DFT) calculations, we show that adsorbed propane sigma
complexes preferentially adopt geometries on PdO(101) in which only primary C-H
bonds datively interact with the surface Pd atoms at low propane coverages and
are thus activated under typical catalytic reaction conditions. We show that a
propane molecule achieves maximum stability on PdO(101) by adopting a bidentate
geometry in which a H-Pd dative bond forms at each CH3 group. These results
demonstrate that structural registry between the molecule and surface can
strongly influence the selectivity of a metal oxide surface in activating alkane
C-H bonds.
PMID- 26420575
TI - Long noncoding RNAs could be potential key players in the pathophysiology of
Sjogren's syndrome.
AB - Long noncoding RNAs (lncRNAs) are a recently discovered class of noncoding
functional RNAs encoded by metazoan genomes. Recent studies suggest a larger
regulatory role for lncRNAs in critical biological and disease processes.
Mounting evidence on the role of lncRNAs in regulating key processes of the
immune system prompted us to hypothesize the role of lncRNAs as key regulators of
the pathophysiology of Sjogren's syndrome (SS). We used two similar approaches
based on reanalysis of microarray expression datasets and curation of lncRNA
protein coding gene interactions from literature to derive support for our
hypothesis. We also discuss potential caveats to our approach and suggest
approaches to validate the hypothesis. Our analysis suggests the potential larger
and hitherto unknown role of lncRNA regulatory networks in modulating the
expression of key genes involved in the pathogenesis of SS and thereby modulating
the pathophysiology of SS.
PMID- 26420574
TI - Amygdala and cingulate structure is associated with stereotype on sex-role.
AB - Sex-role egalitarianism (SRE) is the belief that the sex of an individual should
not influence the perception of his or her rights, abilities, obligations, and
opportunities. Thus, low SRE reflects a more conservative stereotypical view on
sex-role. Here we investigated anatomical correlates of individual differences in
SRE in the present study. We used voxel-based morphometry, a questionnaire to
determine an individual's SRE and associated psychological measures, and
determined the association of SRE with gray matter structures and their cognitive
nature in healthy individuals (375 men and 306 women; age, 20.6 +/- 1.8 years).
We demonstrated that higher SRE was associated with smaller regional gray matter
density (rGMD) in the anterior part of the posterior cingulate cortex (PCC) and
higher rGMD in the right amygdala. Post-hoc analyses revealed psychological
measures characterized by contentious interpersonal orientations, such as
contentious achievement motivation, were associated with lower SRE and higher
rGMD in the anterior part of PCC. Depressive tendencies were associated with
lower SRE and higher rGMD in the right amygdala. These findings suggest that
variations in stereotype on sex role have roots in the limbic brain structures
linked to contentious interpersonal orientation (cingulate) and negative mood
(amygdala).
PMID- 26420577
TI - Optimisation of a treat-to-target approach in rheumatoid arthritis: strategies
for the 3-month time point.
AB - BACKGROUND: Treat-to-target (T2T) is a widely accepted management strategy for
rheumatoid arthritis (RA) with a key decision point at 3 months after treatment
initiation. At this time point, it remains unclear which patients will benefit
from treatment adaptation or from continuation of existing treatment. METHODS: We
performed a pooled analysis of patient-level clinical trial data of patients with
RA. We used a diagnostic testing methodology and a probabilistic approach
employing logistic regression to investigate which levels of response at 3 months
can inform treatment decisions in regard to achieving the target at 6 months.
RESULTS: To be at least 80% sensitive for achieving the low disease activity
(LDA) target at 6 months, a change at 3 months in Simplified Disease Activity
Index/Clinical Disease Activity Index (SDAI or CDAI) of 58% needs to be observed
at 3 months. Higher changes are needed to sensitively predict remission (REM).
Not reaching the (minor) SDAI 50% response level is afflicted with very low
negative likelihood ratios (LRs) (0.28 for LDA and 0.07 for REM at 6 months).
Experiencing (major) SDAI 85% response has substantial positive LRs of 9.2 for
reaching LDA and 6.2 for reaching REM at 6 months. In logistic regression, the
change at 3 months is significantly associated with reaching of the target at 6
months. CONCLUSIONS: The 3-month time point is a critical decision point. Not
achieving minor responses at 3 months makes reaching of the treatment target at 6
months highly unlikely, while reaching major responses is highly predictive of
reaching the treatment target.
PMID- 26420578
TI - Response to: 'Role of nerve growth factor (NGF) and tropomyosin receptor kinase A
(TrkA) in the pathogenesis of osteoarthritis. Might NGF be the link interwinding
obesity and OA?' by Iannone et al.
PMID- 26420579
TI - Mutation in MMP2 gene may result in scleroderma-like skin thickening.
PMID- 26420580
TI - Influence of rice whole-crop silage diet on growth performance, carcass and meat
characteristics and muscle-related gene expression in Japanese Black steers.
AB - The present study investigated the influence of a diet largely comprising rice
whole-crop silage (rWCS) on growth performance, carcass and meat characteristics,
and expression of genes involved in muscle growth of Japanese Black steers.
Steers were randomly separated into rWCS-fed (rWCS ad libitum and restricted
feeding of concentrate) and concentrate-fed groups. Total digestible nutrient
intake and daily gain (DG) decreased in rWCS-fed steers in comparison with
concentrate-fed steers, whereas dressed carcass weight and final body weight did
not significantly differ between the groups. Decreases in drip loss in the muscle
of rWCS-fed steers may be caused by alpha-tocopherol and beta-carotene in muscle.
Feeding large amounts of rWCS to steers may maintain quantitative productivity of
beef steers equally to a concentrate-based diet, and improve the qualitative
productivity. Results of gene expression suggest that activation of skeletal
muscle growth in rWCS-fed steers may occur at the late fattening period owing to
a decrease in myostatin and increase in myosin heavy chain gene expression.
Preadipocyte factor-1 and myostatin genes may be strongly involved in the control
of lipid accumulation. This rearing system would allow beef production to switch
to rWCS-based diets from concentrate-based diets.
PMID- 26420581
TI - The enigma of 'harmful' alcohol consumption: evidence from a mixed methods study
involving female drinkers in Scotland.
AB - BACKGROUND/AIMS: An appreciation of the drinking patterns of population subgroups
may usefully inform tailored interventions. For this purpose, research has
highlighted a need to better describe the drinking behaviour of UK women. This
study aims to characterise the purchasing and consumption behaviour of female
heavy, harmed, drinkers in contact with Scottish health services in two cities
and to explore the factors that influence the link to harm. METHODS: Mixed
methods study involving cross-sectional survey questionnaires and one-to-one
interviews (5). The questionnaires documented (1) demographic data (including
derived deprivation score), last week's (or 'typical' weekly) consumption (type,
brand, volume, price, place of purchase), self-reported illnesses, and (2)
Alcohol-Related Problem Questionnaire score. A total of 181 patients with serious
health problems linked to alcohol were recruited within National Health Service
(NHS) hospital clinics (in- and outpatient settings), in two Scottish cities
during 2012. RESULTS: Median consumption was 157.6 UK units for the recorded
week, with almost exclusive purchase from 'off-sale' retail outlets. Preferred
drinks were white cider, vodka and white wine. Increasing problems was positively
associated with drinking more in the week, being younger and belonging to
Glasgow. CONCLUSION: For Scottish women, the current definition of 'harmful'
consumption likely captures a fourfold variation in alcohol intake, with gender
differences less apparent. While current alcohol-related harm is positively
associated with dose and being younger, there is clear evidence of an influence
of the less tangible 'Glasgow effect'. Future harm concerns are warranted by data
relating to pattern, alcohol dose and cigarette use.
PMID- 26420582
TI - Insomnia symptoms and mortality: a register-linked study among women and men from
Finland, Norway and Lithuania.
AB - Evidence on the association between insomnia symptoms and mortality is limited
and inconsistent. This study examined the association between insomnia symptoms
and mortality in cohorts from three countries to show common and unique patterns.
The Finnish cohort comprised 6605 employees of the City of Helsinki, aged 40-60
years at baseline in 2000-2002. The Norwegian cohort included 6236 participants
from Western Norway, aged 40-45 years at baseline in 1997-1999. The Lithuanian
cohort comprised 1602 participants from the City of Palanga, aged 35-74 years at
baseline in 2003. Mortality data were derived from the Statistics Finland and
Norwegian Cause of Death Registry until the end of 2012, and from the Lithuanian
Regional Mortality Register until the end of 2013. Insomnia symptoms comprised
difficulties initiating sleep, nocturnal awakenings, and waking up too early.
Covariates were age, marital status, education, smoking, alcohol, physical
inactivity, obesity, diabetes, cardiovascular diseases, depression, shift work,
sleep duration, and self-rated health. Cox regression analysis was used. Frequent
difficulties initiating sleep were associated with all-cause mortality among men
after full adjustments in the Finnish (hazard ratio 2.51; 95% confidence interval
1.07-5.88) and Norwegian (hazard ratio 3.42; 95% confidence interval 1.03-11.35)
cohorts. Among women and in Lithuania, insomnia symptoms were not statistically
significantly associated with all-cause mortality after adjustments. In
conclusion, difficulties initiating sleep were associated with mortality among
Norwegian and Finnish men. Variation and heterogeneity in the association between
insomnia symptoms and mortality highlights that further research needs to
distinguish between men and women, specific symptoms and national contexts, and
focus on more chronic insomnia.
PMID- 26420583
TI - Primary pulmonary neoplasia in cats: assessment of computed tomography findings
and survival.
AB - OBJECTIVE: To identify variables with a preoperative computed tomography scan
that influence survival of cats undergoing surgical removal of a primary lung
tumour. A secondary objective was to determine whether histologic type and or
grade of feline pulmonary tumours affects long term survival. METHODS: Medical
records were retrospectively reviewed for cats with preoperative computed
tomography scans and surgical resection of primary lung tumours. Pulmonary
carcinomas were reviewed for histologic diagnosis using two different approaches,
histologic grade as well as major histologic pattern. RESULTS: Median survival
time of all (n = 28) cats was 156 days. Median survival time for cats with lymph
node enlargement was 65 days versus 498 days for cats without lymph node
enlargement on preoperative computed tomography scan. Median survival time for
cats with preoperative pleural effusion was 2 . 5 days versus 467 days for cats
without pleural effusion. Cats with low or intermediate grade tumours had a
median survival time of 730 days versus 105 days for cats with high grade
tumours. CLINICAL SIGNIFICANCE: Cats with preoperative lymph node enlargement and
pleural effusion have shorter survival times than cats without.
PMID- 26420584
TI - Symbolism and ritual practices related to hunting in Maya communities from
central Quintana Roo, Mexico.
AB - BACKGROUND: Some Mayan peasant-hunters across the Yucatan Peninsula in Mexico
still carry out a hunting ritual -Loojil Ts'oon, Loj Ts'oon or Carbine Ceremony-
in which they renew the divine permission for hunting in order to continue
deserving the gift of prey after a period of hunt. Thus they are granted access
to game by the gods and the Lords of the Animals, particularly the spirit/evil
wind call. This paper focuses on the acts within the Loojil Ts'oon -which is
performed in the X-Pichil community and surrounding area- that make it unique
among the hunting rituals performed in other parts of the Peninsula. METHODS: The
Loojil Ts'oon hunting ritual was observed and registered in audiovisual format in
two different occasions in X-Pichil (Friday 04/29/2011 and Friday 07/29/2011).
Afterwards, we delivered digital videodisks (DVD) to hunters and their families
and to the j-men (the magic-medic-ritual specialist) who participated in these
ceremonies. This delivery produced confidence among participants to talk more
openly and in-depth about the Loojil Ts'oon, revealing symbolic, psychological,
and material details previously unknown to outsiders. Qualitative information was
obtained through the ethnographic method using techniques such as participant
observation and guided tours. Semi-structured interviews were carried out to
obtain complementary information. RESULTS AND DISCUSSION: On one hand, we
describe the preparation and cleansing of the "Sip soup", as well as its parading
and distribution -delivery to the spirit/evil-wind Sip- on the streets of the
community (highlingting the role of the rooster as a counter-gift). On the other
hand, the cleansing of the jaws (of deer: Odocoileus virginianus, Mazama spp.;
and peccaries: Tayassuidae) and their return to the Lords of Animals in the hills
so that they may give these animals new life. CONCLUSIONS: By performing the
Loojil Ts'oon, the act of killing an animal is legitimized. The kill transforms
into an exchange to perpetuate life, in which gods and Lords of animals grant the
hunter the solicited new game if he has completed his ritual duties and has not
broken the prescribed hunting rules. The Loojil Ts'oon does not only represent
the continuity and regeneration of animals, that is, fauna as a resource, but
also of the whole hunting cycle. The hunter does so to maintain and recreate
order and equilibrium in one's relationship with nature as a whole, with the rest
of one's social group, and with oneself. Thus, hunting transcends the exclusively
material dimension of a subsistence activity.
PMID- 26420585
TI - Computer-Aided Diagnosis of Parkinson's Disease Using Enhanced Probabilistic
Neural Network.
AB - Early and accurate diagnosis of Parkinson's disease (PD) remains challenging.
Neuropathological studies using brain bank specimens have estimated that a large
percentages of clinical diagnoses of PD may be incorrect especially in the early
stages. In this paper, a comprehensive computer model is presented for the
diagnosis of PD based on motor, non-motor, and neuroimaging features using the
recently-developed enhanced probabilistic neural network (EPNN). The model is
tested for differentiating PD patients from those with scans without evidence of
dopaminergic deficit (SWEDDs) using the Parkinson's Progression Markers
Initiative (PPMI) database, an observational, multi-center study designed to
identify PD biomarkers for diagnosis and disease progression. The results are
compared to four other commonly-used machine learning algorithms: the
probabilistic neural network (PNN), support vector machine (SVM), k-nearest
neighbors (k-NN) algorithm, and classification tree (CT). The EPNN had the
highest classification accuracy at 92.5% followed by the PNN (91.6%), k-NN
(90.8%) and CT (90.2%). The EPNN exhibited an accuracy of 98.6% when classifying
healthy control (HC) versus PD, higher than any previous studies.
PMID- 26420586
TI - Ventilation heterogeneity and the benefits and challenges of multiple breath
washout testing in patients with cystic fibrosis.
AB - Multiple breath inert gas washout tests offer a simple and non-invasive method of
measuring the effects of peripheral airway disease on ventilation efficiency, and
have been the subject of intense research and commercial interest in the last
decade. Although highly sensitive, these tests are not specific to disease in the
small airways and are not suited to all patients with cystic fibrosis. They are
harder to perform in subjects with more severe lung disease, with longer test
time and poorer reproducibility in this population. The clinical advantages are
more obvious in those with milder airways disease, where they are more sensitive
to early changes than spirometry. In this population they are also quicker to
complete and reproducible. A particular advantage in children is a stable range
of normal which does not change during adolescence. Different inert gases give
different washout results, and the technology to measure MBW is itself still
evolving. Newer technologies such as hyperpolarised gas MRI are now helping us to
understand how disease-related changes in lung ventilation influences inert gas
washout.
PMID- 26420587
TI - The Wnt inhibitor dickkopf-1: a link between breast cancer and bone metastases.
AB - Breast cancer is the second leading cause of cancer death in women and
metastasizes to bone in greater than 80 % of advanced-disease patients. Once
breast cancer bone metastases are established, the disease is incurable and
drives numerous complications that increase morbidity and diminish patients'
quality of life. Many mechanisms have been implicated in bone metastases of
breast cancer. The critical role of Wnt signalling pathway inhibition in
initiating bone lesions has been demonstrated in a variety of bone diseases and
tumours. Overexpression of dickkopf-1 (Dkk1) protein, a negative regulator of the
Wnt/beta-catenin pathway, has been found in breast cancer cell lines that form
osteolytic metastases preferentially and in serum from breast cancer patients
with osteolytic bone metastases. Further understanding of the mechanistic role of
Dkk1 as a link between primary breast tumours and secondary osteolytic bone
metastases may facilitate development of anti-Dkk1 antibody therapeutic tools.
PMID- 26420588
TI - Anthelmintic activity of trans-cinnamaldehyde and A- and B-type proanthocyanidins
derived from cinnamon (Cinnamomum verum).
AB - Cinnamon (Cinnamomum verum) has been shown to have anti-inflammatory and
antimicrobial properties, but effects on parasitic worms of the intestine have
not been investigated. Here, extracts of cinnamon bark were shown to have potent
in vitro anthelmintic properties against the swine nematode Ascaris suum.
Analysis of the extract revealed high concentrations of proanthocyanidins (PAC)
and trans-cinnamaldehyde (CA). The PAC were subjected to thiolysis and HPLC-MS
analysis which demonstrated that they were exclusively procyanidins, had a mean
degree of polymerization of 5.2 and 21% of their inter-flavan-3-ol links were A
type linkages. Purification of the PAC revealed that whilst they had activity
against A. suum, most of the potency of the extract derived from CA. Trichuris
suis and Oesophagostomum dentatum larvae were similarly susceptible to CA. To
test whether CA could reduce A. suum infection in pigs in vivo, CA was
administered daily in the diet or as a targeted, encapsulated dose. However,
infection was not significantly reduced. It is proposed that the rapid absorption
or metabolism of CA in vivo may prevent it from being present in sufficient
concentrations in situ to exert efficacy. Therefore, further work should focus on
whether formulation of CA can enhance its activity against internal parasites.
PMID- 26420589
TI - Localization of Hippo signalling complexes and Warts activation in vivo.
AB - Hippo signalling controls organ growth and cell fate by regulating the activity
of the kinase Warts. Multiple Hippo pathway components localize to apical
junctions in epithelial cells, but the spatial and functional relationships among
components have not been clarified, nor is it known where Warts activation
occurs. We report here that Hippo pathway components in Drosophila wing imaginal
discs are organized into distinct junctional complexes, including separate
distributions for Salvador, Expanded, Warts and Hippo. These complexes are
reorganized on Hippo pathway activation, when Warts shifts from associating with
its inhibitor Jub to its activator Expanded, and Hippo concentrates at Salvador
sites. We identify mechanisms promoting Warts relocalization, and using a phospho
specific antisera and genetic manipulations, identify where Warts activation
occurs: at apical junctions where Expanded, Salvador, Hippo and Warts overlap.
Our observations define spatial relationships among Hippo signalling components
and establish the functional importance of their localization to Warts
activation.
PMID- 26420590
TI - Acute effects of calcium supplements on blood pressure and blood coagulation:
secondary analysis of a randomised controlled trial in post-menopausal women.
AB - Recent evidence suggests that Ca supplements increase the risk of cardiovascular
events, but the mechanism(s) by which this occurs is uncertain. In a study
primarily assessing the effects of various Ca supplements on blood Ca levels, we
also investigated the effects of Ca supplements on blood pressure and their acute
effects on blood coagulation. We randomised 100 post-menopausal women to 1 g/d of
Ca or a placebo containing no Ca. Blood pressure was measured at baseline and
every 2 h up to 8 h after their first dose and after 3 months of supplementation.
Blood coagulation was measured by thromboelastography (TEG) in a subgroup of
participants (n 40) up to 8 h only. Blood pressure declined over 8 h in both the
groups, consistent with its normal diurnal rhythm. The reduction in systolic
blood pressure was smaller in the Ca group compared with the control group by >5
mmHg between 2 and 6 h (P<=0.02), and the reduction in diastolic blood pressure
was smaller at 2 h (between-groups difference 4.5 mmHg, P=0.004). Blood
coagulability, assessed by TEG, increased from baseline over 8 h in the calcium
citrate and control groups. At 4 h, the increase in the coagulation index was
greater in the calcium citrate group compared with the control group (P=0.03),
which appeared to be due to a greater reduction in the time to clot initiation.
These data suggest that Ca supplements may acutely influence blood pressure and
blood coagulation. Further investigation of this possibility is required.
PMID- 26420591
TI - Clostridium luticellarii sp. nov., isolated from a mud cellar used for producing
strong aromatic liquors.
AB - A strictly anaerobic, Gram-stain-positive bacterium, designated FW431T, was
isolated from a mud cellar used for producing strong aromatic Chinese liquors.
The strain was able to produce butanoic acid, an important component of the aroma
style of Chinese liquors. Cells of strain FW431T were straight or slightly curved
rods with a polar endospore and peritrichous flagella. The major cellular fatty
acids (>10 % of the total) were C16 : 0, C18 : 1omega9c and C18 : 0. Biolog
assays indicated that the strain preferably metabolizes palatinose, l-fucose,
beta-hydroxybutyric acid, l-rhamnose and alpha-ketobutyric acid among 95 carbon
sources tested. FW431T was related most closely to Clostridium ljungdahlii DSM
13528T and Clostridium kluyveri DSM 555T based on 16S rRNA gene sequence
similarities of 95.0 and 94.2 %, respectively. The DNA G+C content of the genomic
DNA was 44.4 mol%. Based on the evidence presented here, FW431T ( = CGMCC 1.5201T
= KCTC 15519T) is proposed as the type strain of a novel species, Clostridium
luticellarii sp. nov.
PMID- 26420592
TI - Cysteine Enhances Bioavailability of Copper to Marine Phytoplankton.
AB - Emiliania huxleyi, a ubiquitous marine algae, was cultured under replete and Cu
limiting conditions to investigate Cu uptake strategies involving thiols and
associated redox reactions; comparisons to a model diatom, Thalassiosira
pseudonana, were also drawn. Cu-limitation increased rates of cell surface
reduction of Cu(II) to Cu(I) in E. huxleyi but not in T. pseudonana. Furthermore,
Cu-limited E. huxleyi cells took up more Cu when cysteine was present compared to
when no ligand was added, although a dependence on cysteine concentration was not
observed. In contrast, Cu uptake by replete cells was dependent upon the relative
abundance of inorganic species [Cu(I)']. We also show that cysteine can increase
the bioavailability of Cu to Cu-limited cells, of both species, through the
reductive release of Cu(I) from fairly strong Cu(II) ligands such as EDTA.
Finally, support for a mechanism involving uptake of a Cys-Cu complex in E.
huxleyi is drawn from the observation that Cu-limitation significantly enhances
cysteine uptake by transporters that exhibit Michaelis-Menten kinetics. These Cu
uptake strategies help explain the presence and distribution of dissolved thiols
in surface seawater and have implications for the biogeochemical cycling of Cu in
low Cu environments.
PMID- 26420593
TI - Real-time characterization of risks of death associated with the Middle East
respiratory syndrome (MERS) in the Republic of Korea, 2015.
AB - BACKGROUND: An outbreak of the Middle East respiratory syndrome (MERS),
comprising 185 cases linked to healthcare facilities, occurred in the Republic of
Korea from May to July 2015. Owing to the nosocomial nature of the outbreak, it
is particularly important to gain a better understanding of the epidemiological
determinants characterizing the risk of MERS death in order to predict the
heterogeneous risk of death in medical settings. METHODS: We have devised a novel
statistical model that identifies the risk of MERS death during the outbreak in
real time. While accounting for the time delay from illness onset to death, risk
factors for death were identified using a linear predictor tied to a logit model.
We employ this approach to (1) quantify the risks of death and (2) characterize
the temporal evolution of the case fatality ratio (CFR) as case ascertainment
greatly improved during the course of the outbreak. RESULTS: Senior persons aged
60 years or over were found to be 9.3 times (95% confidence interval (CI), 5.3
16.9) more likely to die compared to younger MERS cases. Patients under treatment
were at a 7.8-fold (95% CI, 4.0-16.7) significantly higher risk of death compared
to other MERS cases. The CFR among patients aged 60 years or older under
treatment was estimated at 48.2% (95% CI, 35.2-61.3) as of July 31, 2015, while
the CFR among other cases was estimated to lie below 15%. From June 6, 2015,
onwards, the CFR declined 0.3-fold (95% CI, 0.1-1.1) compared to the earlier
epidemic period, which may perhaps reflect enhanced case ascertainment following
major contact tracing efforts. CONCLUSIONS: The risk of MERS death was
significantly associated with older age as well as treatment for underlying
diseases after explicitly adjusting for the delay between illness onset and
death. Because MERS outbreaks are greatly amplified in the healthcare setting,
enhanced infection control practices in medical facilities should strive to
shield risk groups from MERS exposure.
PMID- 26420594
TI - The prognostic role of pre-cystectomy hemoglobin levels in patients with invasive
bladder cancer.
AB - PURPOSE: To determine whether pre-treatment hemoglobin (Hb) levels in patients
with bladder cancer impact on oncological outcomes after radical cystectomy (RC).
METHODS: A consecutive, contemporary series of 246 patients undergoing RC and
pelvic lymph node dissection for bladder cancer. Decreased Hb level was defined
as <=12 g/dL. The Kaplan-Meier method was used to estimate recurrence-free (RFS),
cancer-specific (CSS) and overall survival (OS). The Fisher exact/Chi-square test
was used to investigate differences between both groups. Uni- and multivariable
Cox regression analysis addressed risk factors for recurrence, cancer-specific
death and overall death. The median follow-up was 30 months (2-116). RESULTS: Of
the 246 patients, 182 (74 %) had normal (>12 g/dL) and 64 decreased (<=12 g/dL)
preoperative Hb (26 %). In univariable analysis, decreased Hb was associated with
increased age, extravesical disease, hydronephrosis (all p < 0.001), node
positive disease and positive resection margins (both p = 0.01). Subanalyzed for
patients with organ-confined disease (defined as <=pT2bN0R0; N = 109), the 3-year
RFS, CSS and OS was significantly lower in patients with decreased (34.9, 35.5
and 19.8 %) compared to normal Hb level (69.7, 86.3 and 77.6 %; p = 0.01/p =
0.002/p < 0.001). In multivariable analysis, RFS, CSS and OS were significantly
lower in patients with decreased Hb (p = 0.007, p = 0.001 and p = 0.002),
pathologically locally advanced tumor (>=pT3a; p = 0.023, p = 0.036 and p =
0.065) and nodal stage (p < 0.001, p = 0.006 and p = 0.001) and positive soft
tissue surgical margins (p = 0.040, p = 0.004 and 0.012). CONCLUSIONS: Pre
cystectomy Hb levels are associated with adverse histopathologic characteristics
and provide additional prognostic information especially for patients with
pathologically localized bladder cancer.
PMID- 26420595
TI - PREDICT: model for prediction of survival in localized prostate cancer.
AB - PURPOSE: Current models for prediction of prostate cancer-specific survival do
not incorporate all present-day interventions. In the present study, a pre
treatment prediction model for patients with localized prostate cancer was
developed. METHODS: From 1989 to 2008, 3383 patients were treated with I-125
brachytherapy (n = 1694), external beam radiotherapy (>=74 Gy, n = 336) or
radical prostatectomy (n = 1353). Pre-treatment parameters (clinical T-stage,
biopsy grade, PSA and age) were related to the hazard of mortality by
multivariate Cox proportional hazard analysis. The PRetreatment Estimation of the
risk of Death In Cancer of the prosTate (PREDICT) model was developed. The
predictive accuracy of the model was assessed by calibration and discrimination
and compared to the Ash risk classification system. RESULTS: Of the 3383 patients
analyzed, 2755 patients (81 %) were alive at the end of follow-up, 149 patients
(4 %) died of prostate cancer and 365 patients (11 %) died of other causes, and
for 114 patients (3 %) cause of death was unknown. Median follow-up time was 7.6
years. After correction for overoptimism, the c-statistic of the prediction model
for prostate cancer-specific mortality was 0.78 (95 % CI 0.74-0.82), compared to
0.78 (95 % CI 0.75-0.81) for the risk classification system by Ash et al. The
PREDICT model showed better calibration than the Ash risk classification system.
CONCLUSIONS: The PREDICT model showed a good predictive accuracy and reliability.
The PREDICT model might be a promising tool for physicians to predict disease
specific survival prior to any generally accepted intervention in patients with
localized prostate cancer.
PMID- 26420596
TI - Extended versus limited pelvic lymph node dissection during bilateral nerve
sparing radical prostatectomy and its effect on continence and erectile function
recovery: long-term results and trifecta rates of a comparative analysis.
AB - PURPOSE: To assess continence and erectile function (EF) recovery of extended
pelvic lymph node dissection (ePLND) versus limited PLND (lPLND) after bilateral
nerve-sparing radical prostatectomy (BNSRP). METHODS: Consecutive prostate cancer
(PCa) patients undergoing BNSRP were stratified according to D'Amico into two
groups: low-risk-PCa lPLND (obturator) and intermediate-/high-risk-PCa ePLND
(obturator, external iliac artery, internal iliac artery, common iliac artery).
Continence (no pad/one safety pad) and EF (IIEF-5 >= 17) recovery were assessed.
Patients with phosphodiesterase type 5 inhibitors, neoadjuvant/adjuvant therapy,
positive lymph nodes or positive surgical margins were excluded. RESULTS: From
January 2007 to May 2012, a total 966 consecutive patients were included. Four
hundred and sixty patients met the inclusion/exclusion criteria: 262 patients had
ePLND and 198 patients had lPLND. Mean number of lymph nodes was 20.4 (range 10
65) and 4.7 (range 0-10), respectively (p < 0.001). Continence and spontaneous EF
recovery after 12 months were 89.7 versus 93.4 % and 40.4 versus 47.5 %,
respectively (all p > 0.05). Patient age at surgery (p = 0.001), preoperative EF
(p < 0.001) and pathological tumor stage (p = 0.008), but not ePLND (p = 0.561),
were independent predictors of EF recovery. No association was detected for
continence recovery. Seven-year BCR-free survival for pT2 PCa was 100 and 94.8 %
in lPLND and ePLND, respectively (p = 0.011). For pT3 PCa, this was 94.7 and 81.2
%, respectively (p = 0.287). At 2 years, the trifecta of continence, potency and
recurrence freedom was achieved in 47.5 and 44.1 % in lPLND and ePLND,
respectively (p = 0.451). CONCLUSIONS: ePLND is not associated with increased
risk of postoperative incontinence or erectile dysfunction. Only patient age at
surgery, preoperative EF and pathological tumor stage represent predictors of EF
recovery.
PMID- 26420597
TI - Is the smoke-free protections glass half full or half empty?
PMID- 26420598
TI - Calcium intake and bone mineral density: systematic review and meta-analysis.
AB - OBJECTIVE: To determine whether increasing calcium intake from dietary sources
affects bone mineral density (BMD) and, if so, whether the effects are similar to
those of calcium supplements. DESIGN: Random effects meta-analysis of randomised
controlled trials. DATA SOURCES: Ovid Medline, Embase, Pubmed, and references
from relevant systematic reviews. Initial searches were undertaken in July 2013
and updated in September 2014. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:
Randomised controlled trials of dietary sources of calcium or calcium supplements
(with or without vitamin D) in participants aged over 50 with BMD at the lumbar
spine, total hip, femoral neck, total body, or forearm as an outcome. RESULTS: We
identified 59 eligible randomised controlled trials: 15 studied dietary sources
of calcium (n=1533) and 51 studied calcium supplements (n=12,257). Increasing
calcium intake from dietary sources increased BMD by 0.6-1.0% at the total hip
and total body at one year and by 0.7-1.8% at these sites and the lumbar spine
and femoral neck at two years. There was no effect on BMD in the forearm. Calcium
supplements increased BMD by 0.7-1.8% at all five skeletal sites at one, two, and
over two and a half years, but the size of the increase in BMD at later time
points was similar to the increase at one year. Increases in BMD were similar in
trials of dietary sources of calcium and calcium supplements (except at the
forearm), in trials of calcium monotherapy versus co-administered calcium and
vitamin D, in trials with calcium doses of >= 1000 versus <1000 mg/day and <= 500
versus >500 mg/day, and in trials where the baseline dietary calcium intake was
<800 versus >= 800 mg/day. CONCLUSIONS: Increasing calcium intake from dietary
sources or by taking calcium supplements produces small non-progressive increases
in BMD, which are unlikely to lead to a clinically significant reduction in risk
of fracture.
PMID- 26420599
TI - Interaction type influences ecological network structure more than local abiotic
conditions: evidence from endophytic and endolichenic fungi at a continental
scale.
AB - Understanding the factors that shape community assembly remains one of the most
enduring and important questions in modern ecology. Network theory can reveal
rules of community assembly within and across study systems and suggest novel
hypotheses regarding the formation and stability of communities. However, such
studies generally face the challenge of disentangling the relative influence of
factors such as interaction type and environmental conditions on shaping
communities and associated networks. Endophytic and endolichenic symbioses,
characterized by microbial species that occur within healthy plants and lichen
thalli, represent some of the most ubiquitous interactions in nature. Fungi that
engage in these symbioses are hyperdiverse, often horizontally transmitted, and
functionally beneficial in many cases, and they represent the diversification of
multiple phylogenetic groups. We evaluated six measures of ecological network
structure for >4100 isolates of endophytic and endolichenic fungi collected
systematically from five sites across North America. Our comparison of these co
occurring interactions in biomes ranging from tundra to subtropical forest showed
that the type of interactions (i.e., endophytic vs. endolichenic) had a much more
pronounced influence on network structure than did environmental conditions. In
particular, endophytic networks were less nested, less connected, and more
modular than endolichenic networks in all sites. The consistency of the network
structure within each interaction type, independent of site, is encouraging for
current efforts devoted to gathering metadata on ecological network structure at
a global scale. We discuss several mechanisms potentially responsible for such
patterns and draw attention to knowledge gaps in our understanding of networks
for diverse interaction types.
PMID- 26420601
TI - Association between HIV infection and bone mineral density in climacteric women.
AB - A cross-sectional study was conducted with the purpose of evaluating bone mineral
density in HIV seropositive and seronegative climacteric women. HIV infection was
negatively associated with bone mineral density in the lumbar spine PURPOSE: To
assess bone mineral density (BMD) and its associated factors in HIV seropositive
and seronegative climacteric women METHODS: A cross-sectional study with 537
women (273 HIV seropositive and 264 HIV seronegative) aged between 40 and 60
years old receiving follow-up care at two hospitals in Brazil. A questionnaire on
clinical and sociodemographic characteristics was completed. Laboratory tests
were performed, and BMD was measured at the lumbar spine and hip. Statistical
analysis was carried out by Yates and Pearson chi-squared tests, Mann-Whitney
test, and multiple linear regression. RESULTS: The mean age was 47.7 years in HIV
seropositive women, and 75 % had nadir CD4 above 200, and 77.8 % had viral load
below the detection limit. The mean age in the HIV-seronegative women was 49.8
years. The prevalence of low spinal BMD was 14.6 % in the HIV-seropositive and
4.6 % in the HIV-seronegative women (p < 0.01). The prevalence of low BMD at the
femoral neck was 5.6 % in HIV-seropositive and 3.3 % in the HIV-seronegative
women (p = 0.38). Multiple analyses showed that the factors associated with lower
BMD at the spine were being postmenopausal and being HIV-seropositive. Being
overweight was associated with a higher BMD. At the femoral neck, factors
associated with lower BMD were being postmenopausal and being white. Being
overweight and having a greater number of pregnancies were associated with higher
BMD CONCLUSIONS: HIV-seropositive women on long-term antiretroviral treatment and
in good immunological conditions exhibited low BMD in the spine (L1-L4). However,
BMD in the femoral neck was similar to non-infected women.
PMID- 26420600
TI - [Kyphoplasty combined with intraoperative radiotherapy (Kypho-IORT). Alternative
therapy for patients with oligometastatic spinal metastases].
AB - BACKGROUND: Due to a more effective systemic therapy the survival of patients
suffering from malignant tumors has been significantly improved but a longer life
span is often associated with a higher incidence of osseous metastases. The
majority of these metastases are localized in the spine causing pain, instability
and neurological impairments. The interdisciplinary management of spinal
metastases previously consisted of stabilization followed by fractionated
external body radiation therapy. A reduction in procedural severity and morbidity
as well as consideration of self-sufficiency and hospitalization time are
important target parameters for these palliative patients. METHOD AND RESULTS:
Kyphoplasty combined with intraoperative radiotherapy (Kypho-IORT) is one of
several modern treatment options, which involves a minimally invasive procedure
with local high-dose transpedicular irradiation of the spine with low-energy (50
kV) X-rays. Immediately following irradiation, stabilization of the spine is
carried out using kyphoplasty via the same access route so that a single stage
procedure with excellent pain reduction and good local tumor control can be
achieved. This article presents clinical data for this procedure and the
different fields of indications are critically reviewed and compared to other
therapy options. Methodological improvements and options for further
individualization of therapy are demonstrated. CONCLUSION: The Kypho-IORT
procedure is a safe, feasible and beneficial modern treatment option for instant
stabilization and local tumor control in patients with spinal metastases. More
than 100 operations have been successfully performed so that the method can be
deemed suitable for inclusion in the clinical routine. A phase II dose escalation
study has now been completed and submitted for publication and a 2-arm non
inferiority trial (phase III study) for comparison with conventional irradiation
is in progress.
PMID- 26420602
TI - Assessment of susceptibility of mould isolates towards biocides.
AB - OBJECTIVES: The aim of this study was to determine the susceptibility of 77 mould
strains: Aspergillus fumigatus (20), Aspergillus flavus (8), Aspergillus niger
(4), Aspergillus ochraceus (2), Penicillium citrinum (15), Penicillium crysogenum
(14), Penicillium aurantiogriseum (1), Penicillium roquefortii (4), Penicillium
paneum (2), Rhizopus spp. (3), Tricoderma spp. (1) and Mucor spp. (3) to
biocides. METHODS: MIC determination was determined based on CLSI methodology.
RESULTS: For hospital acquired strains, MIC50 was 0.5mg/L, MIC90 was 1mg/L for
chlorhexidine (CHX); MIC50 was 0.5mg/L, and MIC90 was 1mg/L for benzalkonium
chloride (BZC); MIC50 was 1mg/L, and MIC90 was 2mg/L for triclosan (TRC); MIC50
was 1024mg/L, and MIC90 was 2048mg/L for sodium hypochloride (SHC). For feed and
food isolates MIC50 was 2mg/L, MIC90 was 8mg/L for CHX, MIC50 was 2mg/L, and
MIC90 was 4mg/L for BZC, MIC50 was 2mg/L, and MIC90 was 4mg/L for TRC, MIC50 was
256mg/L, and MIC90 was 512mg/L for SHC. CONCLUSION: We can conclude that food
isolates presented slightly higher MIC50 and MIC90 values for CHX, BNZ and TRC,
but not for SHC.
PMID- 26420603
TI - Targeted Gene Delivery to Macrophages by Biodegradable Star-Shaped Polymers.
AB - In this report, two biodegradable star-shaped polyasparamide derivatives and four
analogues modified with either mannose or folic acid moiety for preferential
targeting of a difficult-to-transfect immune cell type, i.e., macrophage, have
been synthesized. Each of the prepared star polymers complexes with plasmid DNA
to form nanosized particles featuring a core-shell-like morphology. Mannose or
folate functionalized star polymers can greatly improve the transfection
performance on a macrophage cell line RAW 264.7. As a result, a combination of
targeting ligand modification and topological structures of gene carriers is a
promising strategy for immune cells-based gene therapy.
PMID- 26420604
TI - Ochratoxin A in brewer's yeast used as food supplement.
AB - Brewer's yeasts are rich in vitamins of the B-group and contain other nutritive
factors; therefore, they are recommended as valuable food supplements for people
with special dietary requirements like pregnant women, children, and adolescents,
or for people with high physical activity. Additionally, certain strains of
brewer's yeast are known to be capable of adsorbing xenobiotics such as
mycotoxins. Because of that, these yeasts are regarded as having positive effects
in food, beverage, and feed technology. Their potential to bind mycotoxins such
as ochratoxin A (OTA), however, can subsequently lead to a contamination of such
brewer's yeasts used as food supplements. In the present study, we analyzed 46
samples of brewer's yeasts for the occurrence of OTA by HPLC with fluorescence
detector (HPLC-FLD) and for confirmatory measurements by liquid chromatography
tandem mass spectrometry (LC-MS/MS). Nearly 90% of the samples were contaminated
with OTA, the levels ranging from the limit of detection (LOD, 0.01 MUg/kg) to
4.2 MUg/kg. The mean and median levels of contamination were 0.49 and 0.27
MUg/kg, respectively. Based on these results, the additional weekly OTA exposure
by regularly consuming such supplements was assessed. Depending on different
subpopulations (adults, children) and levels of contamination used for
calculation, the additional OTA intake via brewer's yeast products ranged from
9.3% (mean case) to 114% (worst case) of the published mean weekly OTA intake in
Germany (adults 279.3 ng, children 195.3 ng). At present, maximum levels for OTA
in nutritional supplements like brewer's yeast do not exist. Based on our
results, however, it is recommended that producers of these dietary supplements
should include mycotoxin analyses in ongoing and future self-monitoring programs
and in product quality checks.
PMID- 26420605
TI - Effects of deoxynivalenol in naturally contaminated wheat on feed intake and
health status of horses.
AB - The present study examined the short-term effects of deoxynivalenol (DON),
administered at two different concentrations via a feed preparation using
naturally contaminated wheat, on feed intake, liver and kidney metabolism and
immunomodulatory properties in horses. Twelve geldings were randomly assigned to
one of three dietary treatments for 21 days. DON was provided via naturally
contaminated wheat (14.6 +/- 6.5 mg DON/kg dry matter). The daily feed intake was
adjusted to 4 kg of wheat and 1.7 kg of silage per 100 kg of body weight (BW).
Horses were fed one of the following diets: control wheat with 0% contaminated
wheat (CON), wheat mixture containing 53 +/- 2% of DON-contaminated wheat [low
DON intake (LDI)] or wheat mixture containing 78 +/- 4% of DON-contaminated wheat
[high DON intake (HDI)]. CON, LDI and HDI corresponded to a targeted daily DON
intake via the complete ration of <5, 50 and 75 MUg/kg BW, respectively. None of
the horses demonstrated any clinical signs commonly associated with the intake of
DON such as colic or depression. HDI was associated with lower daily wheat intake
on day 21. Serum DON concentrations increased with higher DON intake. The non
toxic DON metabolite, deepoxy-deoxynivalenol (DOM-1) was only detected on day 21
of the DON feeding period. No changes in haematological and serum parameters or
serum globulins or in the ex vivo proliferation response of peripheral blood
mononuclear cells were observed. These results suggest that horses are less
sensitive to DON exposure than other domestic species, for example, swine.
Therefore, the European Commission guidance value for critical DON concentrations
in swine feed (complete diet) of 0.9 mg/kg could be safely applied for rations
intended for feeding adult horses as well.
PMID- 26420606
TI - A Toxoplasma gondii vaccine encoding multistage antigens in conjunction with
ubiquitin confers protective immunity to BALB/c mice against parasite infection.
AB - BACKGROUND: Toxoplasma gondii is a widely prevalent intracellular parasite which
infects almost all warm-blooded animals including humans and causes serious
zoonotic toxoplasmosis. DNA vaccines have proved effective in the protection
against parasites. However, the problems of weak immunity and inefficient
delivery of DNA vaccine remain major issues. Therefore, comprehensive antigens
derived from all stages of the parasite, effective adjuvants and delivery systems
should be considered in the vaccine construction. METHODS: SAG3101-144,ROP18347
396, MIC6288-347, GRA7182-224, MAG158-125, BAG1156-211 and SPA142-200, derived
from antigens in tachyzoite, bradyzoite and sporozoite stages of T. gondii were
screened based on CD8(+) T cell epitope binding affinity to HLA and H-2. We
constructed a recombinant DNA vaccine and an adenovirus vaccine encoding multi
stage antigen of T. gondii linked to ubiquitin molecules and vaccinated BALB/c
mice with different strategies. Antibodies, cytokines, splenocytes proliferation,
as well as the percentage of CD4(+) and CD8(+) T cells in immunized mouse were
analyzed by the Enzyme-Linked Immunosorbent Assays (ELISA), Flow Cytometry (FCM).
Protective efficacy was evaluated by challenging immunized mice with type I and
type II parasite. RESULTS: Our results indicated that the DNA vaccine had the
advantage of inducing a stronger humoral response, whereas the adenovirus
vectored vaccine effectively improved the cellular immune response. Priming with
DNA vaccine and boosting with adenovirus-vectored vaccine induced Th1-type immune
responses with highest levels of IgG2a and secretion of cytokines IL-2 and IFN
gamma. Effective protection against type I and type II parasite with an increase
in survival rate and a decrease in brain cyst burden was achieved in immunized
mice. CONCLUSIONS: Priming vaccination with DNA vaccine and boosting with the
recombinant adenovirus vaccine encoding ubiquitin conjugated multi-stage antigens
of T. gondii was proved to be a potential strategy against the infection of type
I and type II parasite.
PMID- 26420609
TI - Integration, Networking, and Global Biobanking in the Age of New Biology.
AB - Scientific revolution is changing the world forever. Many new disciplines and
fields have emerged with unlimited possibilities and opportunities. Biobanking is
one of many that is benefiting from revolutionary milestones in human genome,
post-genomic, and computer and bioinformatics discoveries. The storage,
management, and analysis of massive clinical and biological data sets cannot be
achieved without a global collaboration and networking. At the same time,
biobanking is facing many significant challenges that need to be addressed and
solved including dealing with an ever increasing complexity of sample storage and
retrieval, data management and integration, and establishing common platforms in
a global context. The overall picture of the biobanking of the future, however,
is promising. Many population-based biobanks have been formed, and more are under
development. It is certain that amazing discoveries will emerge from this large
scale method of preserving and accessing human samples. Signs of a healthy
collaboration between industry, academy, and government are encouraging.
PMID- 26420607
TI - The association between temporal changes in the use of obstetrical intervention
and small-for-gestational age live births.
AB - BACKGROUND: The literature attributes secular declines in small-for-gestational
age (SGA) live births to changes in maternal smoking and other maternal
characteristics. However, there are reasons to believe that the observed
reductions in SGA may be a consequence of early delivery following obstetric
intervention. METHODS: We examined temporal trends in obstetrical intervention
and SGA among singleton live births in the United States from 1990 to 2010. The
modified Kitagawa decomposition, based on the fetuses-at-risk approach, was used
to assess the relative contribution of changes in the gestational age
distribution and gestational age-specific SGA to overall changes in SGA.
Reductions in SGA rates due to a left shift in the gestational age distribution
were assumed to primarily reflect increased obstetrical intervention, whereas
decreases in overall SGA due to decreases in gestational-age-specific SGA rates
were assumed to reflect declines in risk factors. RESULTS: Temporal trends in SGA
followed a non-linear pattern, with substantial declines from 10.1% in 1990-92 to
8.9% in 2002-04, followed by a small increase to 9.1% in 2008-10. Rates of
maternal smoking steadily decreased throughout the same time period and changes
in SGA rates were more consistent with changes in the gestational age
distribution. The modified Kitagawa decomposition analysis also attributed the
initial decline in SGA rates to changes in the gestational age distribution.
CONCLUSIONS: Complex temporal pattern in SGA rates cannot be explained by the
linear pattern of changes in factors like maternal smoking. Changes in the
gestational age distribution are more consistent with the observed secular trends
in SGA rates.
PMID- 26420608
TI - Granulosa cell apoptosis by impairing antioxidant defense system and cellular
integrity in caprine antral follicles post malathion exposure.
AB - Toxicological studies have demonstrated the exposure-risk relationship of several
pesticides on reproduction of living organisms. To evaluate the role of malathion
as a reproductive toxicant, this study aims at assessing the cytological and
biochemical changes in the granulosa cells after malathion exposure in dose (1
nM, 10 nM, 100 nM) and time (4 h, 6 h, 8 h) dependent manner. Histomorphological
analysis, fluorescence assay, apoptosis quantification, and terminal
deoxynucleotidyl transferase d-UTP mediated nick end labeling (TUNEL) assay were
done to determine cytological changes, whereas antioxidant enzyme assays were
done to measure the oxidative stress in malathion treated ovarian antral
follicles. Histological studies exhibited the occurrence of highly condensed or
marginated chromatin with fragmented nucleus, pyknosis, loss of membrane
integrity, increased empty spaces, and vacuolization in malathion treated
granulosa cells. Ethidium bromide/acridine orange (EB/AO) fluorescence staining
demonstrated a significant increase in incidence and percentage of apoptosis
after malathion exposure (p < 0.001), both between and within the groups.
Malathion exposure also resulted in increased DNA fragmentation and decline in
both antioxidant enzymes activity namely catalase (CAT) and superoxide dismutase
(SOD) in granulosa cells of antral follicles. Moreover, there was found a
significant negative correlation between the apoptosis incidence and the level of
antioxidant enzymes activity, SOD (r = -0.73 p < 0.01) and CAT (r = -0.80 p <
0.01), in malathion treated ovarian antral follicles. Thus, highlighting the role
of DNA fragmentation and declining antioxidant level as a possible mechanism
underlying malathion induced reproductive toxicity. (c) 2015 Wiley Periodicals,
Inc. Environ Toxicol 31: 1944-1954, 2016.
PMID- 26420610
TI - The Future of Biobanking: A Conceptual Look at How Biobanks Can Respond to the
Growing Human Biospecimen Needs of Researchers.
AB - Biobanking of human biological specimens has evolved from the simple private
collection of often poorly annotated residual clinical specimens, to well
annotated and organized collections setup by commercial and not-for-profit
organizations. The activities of biobanks is now the focus of international and
government agencies in recognition of the need to adopt best practices and
provide scientific, ethical and legal guidelines for the industry. The demand for
more, high quality and clinically annotated biospecimens will increase, primarily
due to the unprecedented level of genomic, post genomic and personalized medicine
research activities going on. Demand for more biospecimens provides new
challenges and opportunities for developing strategies to build biobanking into a
business that is better able to supply the biospecimen needs of the future. A
paradigm shift is required particularly in organization and funding, as well as
in how and where biospecimens are collected, stored and distributed. New
collection sites, organized as Research Ready Hospitals (RRHs) and new public
private partnership models are needed for sustainability and increased
biospecimen availability. Biobanks will need to adopt industry-wide standard
operating procedures, better and "non-destructive" methods for quality
assessment, less expensive methods for sample storage/distribution, and objective
methods to manage scarce biospecimens. Ultimately, the success of future biobanks
will rely greatly on the success of public-private partnerships, number and
diversity of available biospecimens, cost management and the realization that an
effective biobank is one that provides high quality and affordable biospecimens
to drive research that leads to better health and quality of life for all.
PMID- 26420611
TI - Sustainability of Biobanks in the Future.
AB - Human biorepositories are essential in providing high quality specimens that are
well characterized. Biospecimens are used in basic, clinical, and translational
research. However, as regulatory requirements and scientific demands increase the
complexity of the daily operations of a biorepository, the cost of maintaining a
biobank will increase. How can biobanks today maintain sustainability during the
current economic climate and changing landscape of operating a biorepository?
This is a brief review of how different biobanks have approached sustainability.
PMID- 26420612
TI - Biobanking: The Future of Cell Preservation Strategies.
AB - With established techniques cryopreservation is often viewed as an "old school"
discipline yet modern cryopreservation is undergoing another scientific and
technology development growth phase. In this regard, today's cryopreservation
processes and cryopreserved products are found at the forefront of research in
the areas of discovery science, stem cell research, diagnostic development and
personalized medicine. As the utilization of cryopreserved cells continues to
increase, the demands placed on the biobanking industry are increasing and
evolving at an accelerated rate. No longer are samples providing for high
immediate post-thaw viability adequate. Researchers are now requiring samples
where not only is there high cell recovery but that the product recovered is
physiologically and biochemically identical to its pre-freeze state at the
genominic, proteomic, structural, functional and reproductive levels. Given this,
biobanks are now facing the challenge of adapting strategies and protocols to
address these needs moving forward. Recent studies have shown that the control
and direction of the molecular response of cells to cryopreservation
significantly impacts final outcome. This chapter provides an overview of the
molecular stress responses of cells to cryopreservation, the impact of the
apoptotic and necrotic cell death continuum and how studies focused on the
targeted modulation of common and/or cell specific responses to freezing
temperatures provide a path to improving sample quality and utility. This line of
investigation has provided a new direction and molecular-based foundation guiding
new research, technology development and procedures. As the use of and the
knowledge base surrounding cryopreservation continues to expand, this path will
continue to provide for improvements in overall efficacy and outcome.
PMID- 26420613
TI - Biobanking for Personalized Medicine.
AB - A biobank is an entity that collects, processes, stores, and distributes
biospecimens and relevant data for use in basic, translational, and clinical
research. Biobanking of high-quality human biospecimens such as tissue, blood and
other bodily fluids along with associated patient clinical information provides a
fundamental scientific infrastructure for personalized medicine. Identification
of biomarkers that are specifically associated with particular medical conditions
such as cancer, cardiovascular disease and neurological disorders are useful for
early detection, prevention, and treatment of the diseases. The ability to
determine individual tumor biomarkers and to use those biomarkers for disease
diagnosis, prognosis and prediction of response to therapy is having a very
significant impact on personalized medicine and is rapidly changing the way
clinical care is conducted. As a critical requirement for personalized medicine
is the availability of a large collection of patient samples with well annotated
patient clinical and pathological data, biobanks thus play an important role in
personalized medicine advancement. The goal of this chapter is to explore the
role of biobanks in personalized medicine and discuss specific needs regarding
biobank development for translational and clinical research, especially for
personalized medicine advancement.
PMID- 26420614
TI - A Global View of Breast Tissue Banking.
AB - The importance of accessing high quality clinical samples for translational
research is now firmly recognised. Traditionally these samples were collected and
curated by individuals with an interest in a particular disease type. In recent
years the idea of centralising and storing tissue collections in the form of
tissue banks or biobanks has developed. As a result a number of biobanks have
been established in many different countries. These can be either single centres
or multi centre collaborations, often in the form of a federated network. This
chapter outlines the development of breast tissue banking in a global context and
discusses some of the challenges that lie ahead for the field, in particular how
to meet the growing needs of researchers, how to make the best use of donated
samples and how to increase the visibility of samples residing in biobanks to
researchers.
PMID- 26420615
TI - Biobanking of Cerebrospinal Fluid for Biomarker Analysis in Neurological
Diseases.
AB - Cerebrospinal fluid (CSF) reflects pathophysiological aspects of neurological
diseases, where neuroprotective strategies and biomarkers are urgently needed.
Therefore, biobanking is very relevant for biomarker discovery and evaluation for
these neurological diseases.An important aspect of CSF biobanking is quality
control, needed for e.g. consistent patient follow-up and the exchange of patient
samples between research centers. Systematic studies to address effects of pre
analytical and storage variation on a broad range of CSF proteins are needed and
initiated.Important features of CSF biobanking are intensive collaboration in
international networks and the tight application of standardized protocols. The
current adoption of standardized protocols for CSF and blood collection and for
biobanking of these samples, as presented in this chapter, enables biomarker
studies in large cohorts of patients and controls.In conclusion, biomarker
research in neurodegenerative diseases has entered a new era due to the
collaborative and multicenter efforts of many groups. The streamlining of
biobanking procedures, including sample collection, quality control, and the
selection of optimal control groups for investigating biomarkers is an important
improvement to perform high quality biomarker studies.
PMID- 26420616
TI - Biobanking in the Twenty-First Century: Driving Population Metrics into
Biobanking Quality.
AB - Biospecimens are the essential substrates for human biomarker research. Across
the globe, biobanks have developed the facilities and mechanisms to collect,
process, store and distribute those substrates to researchers. However, despite
some notable successes, less than one hundred of the tens of thousands of
purported biomarkers have been independently validated. We propose the need for a
new paradigm in biobanking; simply pursuing larger numbers of participants,
larger networks of biobanks and higher sample integrity will not, in itself,
transform the success rate or efficiency of biomarker research. We propose that
biobanks must embrace the intrinsic observational nature of biospecimens and
furnish the recipients of biospecimens with the population metrics (descriptive
statistics) that can facilitate the scientific rigor that is mandated in other
areas of observational research. In addition, we discuss the value of population
based ascertainment and recruitment and the importance of the timing of
biospecimen collections. Any assessment of biospecimen quality must go beyond the
sample itself and consider both the patient/participant selection and the most
appropriate and informative timing for specimen collection, particularly prior to
any treatment intervention in diseased populations. The examples and rationales
that we present are based largely on cancer-related collections because the
feasibility of population metrics is greatly assisted by the comprehensive
registries that are more common for cancer than other chronic diseases. Changing
the biobanking paradigm from tacitly 'experimental' to explicitly 'observational'
represents a profound but urgent methodological shift that will influence the
establishment, management, reporting and impact of biobanks in the twenty-first
century.
PMID- 26420617
TI - Challenges in Developing a Cancer Oriented-Biobank: Experience from a 17 Year-Old
Cancer Biobank in Sao Paulo, Brazil.
AB - Brazil and Latin America will face a cancer epidemic in the coming years. Efforts
towards cancer prevention, early detection and treatment must be associated with
active research that helps understanding the geographical variations of this
disease. The creation of cancer-oriented biobanks should be part of this
strategy. This article outlines the challenges of establishing a cancer-oriented
biobank at the A. C. Camargo Center, a private, non-profit institution located in
Sao Paulo, Brazil. We analyze important issues related to the day-to-day
operations of the biobank within an institutional and national context, as well
as the lessons learned over the years. It is hoped that the information contained
in this paper will be useful for the development of other biobanks in Brazil and
other countries in Latin America.
PMID- 26420618
TI - China Biobanking.
AB - Biobanks are playing increasingly important roles in clinical and translational
research nowadays. China, as a country with the largest population and abundant
clinical resources, attaches great importance to the development of biobanks. In
recent years, with the increasing support from the Chinese government, biobanks
are blooming across the country. This paper provides a detailed overview of China
biobanking, which is further divided in the following four parts: (i) general
introduction of the number, category and distribution of current biobanks; (ii)
summarization of the current development status, and issues that Chinese biobanks
are faced with; (iii) international cooperation between China and the global
biobanking community; (iv) prospect of the modern twenty-first century Chinese
biobanks, which would achieve standardized operation, systematic specimen
management, and extensive collaboration, and thus provide support for the robust
research discoveries and personalized medicine etc.
PMID- 26420619
TI - Establishing an Iso-Compliant Modern Cancer-Biobank in a Developing Country: A
Model for International Cooperation.
AB - King Hussein Cancer (KHCC) is a specialized cancer center that treats both adult
and pediatric cancer patients from Jordan and the neighboring countries. KHCC is
acknowledged as a leader in cancer treatment in the Middle East and its vision is
to maintain its leading position in cancer therapy and research. Hence, KHCC
embarked on establishing the first ISO compliant cancer biobank (KHCCBIO) in
Jordan.Currently, there are very few biobanks in the Middle East, hence, KHCC
wanted to change this situation by establishing an ISO-compliant cancer biobank
which would incorporate all current international guidelines and best-in class
practices under an approved quality management system for the benefit of
researchers in Jordan, its neighboring countries, and throughout the world. The
established biobank would follow the highest ethical standards in collecting,
processing, storing and distributing high-quality, clinically annotated
biospecimens.The strategy used in establishing KHCCBIO was based on taking
advantage of international networking and collaboration. This in essence led to
knowledge transfer between well established organizations, institutions and
individuals from Europe and Jordan, in existing technological innovation and
internationally recognized quality standards. KHCC efforts were facilitated by a
grant from the European Union under the seventh frame work program.Future aims of
KHCCBIO are to develop KHCC's research infrastructure, increase its scope and
visibility and improve its competitiveness throughout the biomedical science
arena. Moreover, KHCCBIO is aiming to establish a platform for future knowledge
transfer and collaborative research; develop partnerships between European and
Middle Eastern organizations.
PMID- 26420620
TI - Nursing and Biobanking.
AB - Nurses are a pivotal component of the translational research movement and apply
scientific discoveries to the healthcare and clinical practice fields. Biobanking
is also an important factor in furthering translational research by providing
biospecimens and related clinical data to the research community. The
effectiveness of any biobanking effort necessitates the enrollment of large
numbers of diverse participants, which signifies a need for the nursing
profession to secure the knowledge necessary to impact biobanking practices and
to promote participant advocacy. In addition, biobanks provide the volume,
variety, veracity, and velocity of data that can address the challenges of
nursing research. Nurse scientists, research nurse coordinators and clinical
research and practice nurses must be informed about the various benefits and
risks associated with biobanking in addition to ethical issues surrounding
informed consent, participant privacy, and the release of research results.
Ultimately, nurses need to possess competencies to facilitate biobanking
practices both at the research bench and at the point of care.
PMID- 26420621
TI - A Data-Centric Strategy for Modern Biobanking.
AB - Biobanking has been in existence for many decades and over that time has
developed significantly. Biobanking originated from a need to collect, store and
make available biological samples for a range of research purposes. It has
changed as the understanding of biological processes has increased and new sample
handling techniques have been developed to ensure samples were fit-for-purpose.As
a result of these developments, modern biobanking is now facing two substantial
new challenges. Firstly, new research methods such as next generation sequencing
can generate datasets that are at an infinitely greater scale and resolution than
previous methods. Secondly, as the understanding of diseases increases
researchers require a far richer data set about the donors from which the sample
originate.To retain a sample-centric strategy in a research environment that is
increasingly dictated by data will place a biobank at a significant disadvantage
and even result in the samples collected going unused. As a result biobanking is
required to change strategic focus from a sample dominated perspective to a data
centric strategy.
PMID- 26420622
TI - The Importance of Quality Patient Advocacy to Biobanks: A Lay Perspective from
Independent Cancer Patients Voice (ICPV), Based in the United Kingdom.
AB - Biobanking in the twentieth century will become of increasing importance in
health research. Regulation and governance of biobanks must be open and
transparent to ensure public trust and confidence and increase donation.
Effective Lay Involvement all levels in biobank organisations should be standard
practice helping ensure patient benefit remains the central aim and assisting the
Promotion of Biobanks and Recruitment of Donors. Properly selected, educated and
supported, they become valued members of the Biobank Team. This chapter is based
on the work of Independent Cancer Patients' Voice (ICPV) in the UK and recognises
that the National Health Service provides a framework which is not universal and
neither is the model of patient advocacy which has been developed particularly in
cancer research. However, although it has not been easy to find potential members
for ICPV, nor to attract funding, we have earned the respect of our professional
colleagues by our commitment in giving time and developing the skills necessary
to provide effective involvement. These colleagues have enthusiastically mentored
and supported us and have provided venues and tutoring for Educational Events. We
are sure that patient advocates in other countries would welcome the opportunity
for similar involvement and hope our experiences will be of interest.
PMID- 26420623
TI - Correction: Treatment Efficacy and Resistance Mechanisms Using the Second
Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell
Lymphoma.
PMID- 26420624
TI - Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate
Progressive beta-Cell Dysfunction and May Be Predictive for Development of Type 2
Diabetes.
AB - BACKGROUND: Elevated fasting intact proinsulin is a biomarker of late-stage beta
cell-dysfunction associated with clinically relevant insulin resistance. In this
pilot investigation, we explored the potential value of measuring intact
proinsulin as a functional predictor of beta-cell exhaustion during an oral
glucose tolerance test (OGTT). METHODS: The study was performed with 31
participants, 11 of whom were healthy subjects (7 female, age: 59 +/- 20 years),
10 had impaired glucose tolerance (IGT, 6 female, 62 +/- 10 years), and 10 had
known type 2 diabetes (T2DM, 5 female, 53 +/- 11 years, HbA1c: 7.0 +/- 0.6%,
disease duration: 8 +/- 5 years). During OGTT, blood was drawn after 0 hours, 1
hour, and 2 hours for determination of glucose and intact proinsulin. Five years
later, patients were again contacted to assess their diabetes status and the
association to the previous OGTT results was analyzed. RESULTS: The OGTT (0
hours/1 hour/2 hours) results were as follows: healthy subjects: glucose: 94 +/-
8 mg/dL/140 +/- 29 mg/dL/90 +/- 24 mg/dL, intact proinsulin: 3 +/- 2 pmol/L/10 +/
7 pmol/L/10 +/- 5 pmol/L); IGT: glucose: 102 +/- 9 mg/dL/158 +/- 57 mg/dL/149 +/
34 mg/dL, intact proinsulin: 7 +/- 4 pmol/L/23 +/- 8 pmol/L/28 +/- 6 pmol/L;
T2DM: glucose: 121 +/- 20 mg/dL/230 +/- 51 mg/dL/213 +/- 34 mg/dL; intact
proinsulin: 7 +/- 7 pmol/L/26 +/- 9 pmol/L/27 +/- 10 pmol/L). Five years later,
all of the IGT and 2 of the healthy subjects had developed T2DM and one had
devloped IGT. All of them had elevated 2-hour proinsulin values in the initial
OGTT, while patients with normal intact proinsulin results did not develop
diabetes. CONCLUSIONS: Elevated 2-hour intact proinsulin levels during OGTT were
predictive for later type 2 diabetes development. Further studies need to confirm
our findings in larger populations.
PMID- 26420625
TI - Using Remote Communication Technology in Insulin Pump Training: A Feasibility
Study.
AB - PURPOSE: This feasibility study was designed to examine if remote communication
technology can be used in the technical training of an insulin pump in adults
with diabetes who were familiar with insulin pump therapy. METHODS: Surveys were
emailed to 69 individuals who purchased an insulin pump and had been trained by
the manufacturer's diabetes educators. In consultation with providers,
participants were given the choice of receiving training in a face-to-face
meeting or via remote communication technology. The survey consisted of 27
questions asking participants' characteristics, device proficiency, confidence,
and their satisfaction with the insulin pump and the training method. Differences
between the 2 groups were examined using bivariate analyses. RESULTS: There were
17 participants in the remote group and 20 participants in the face-to-face
group. Participants had a mean age of 40.9 +/- 14.3 years, had diabetes for 24.3
+/- 13.8 years, and used an insulin pump for 9.8 +/- 4.9 years. The participants
in both groups were not statistically different in age, diabetes history, years
on insulin pump, device proficiency, confidence, or satisfaction with the
training method. The remote group reported less graduate-level education (P <
.05) and higher satisfaction scores with the insulin pump training (P < .05).
CONCLUSION: Although this study has limitations associated with the small sample
size and self-selection bias, the results suggest that remote communication
technology may be an effective tool to provide technical training to adults who
are familiar with insulin pump therapy. Additional research is required to
determine the effectiveness of the remote insulin pump training.
PMID- 26420626
TI - Are Systematic Reviews and Meta-Analyses Appropriate Tools for Assessing Evolving
Medical Device Technologies?
AB - Systematic reviews and meta-analyses (SRMAs) provide unique insights into
comparative effectiveness of diabetes treatments. However, use of these analyses
may be inappropriate for assessing the value and utility of technologies that
involve significant behavioral interventions and encompass rapidly evolving
technologies such as real-time continuous glucose monitoring (RT-CGM). The rapid
evolution of RT-CGM, compared with the time required for publication of clinical
studies used in SRMAs, may preclude differentiation between past and current
generations of devices. In addition, the effect of performance and usability
differences between the various commercial devices on possible clinical outcomes
associated with the devices are often not clearly discussed, and many of the RT
CGM studies assessed in SRMAs do not provide adequate information regarding
whether and/or to what degree study subjects and clinicians were trained to use
the RT-CGM and utilize the data to adjust therapy. Although numerous clinical
studies have shown that the glycemic benefit of RT-CGM is related to the
frequency and duration of use, a disproportionate number of RT-CGM studies
included in recent SRMAs are based on the results of the intention-to-treat
analyses and do not consider this fundamental behavioral component in their
conclusions. Given these limitations, the generalizability of SRMA conclusions
may be limited, and findings from these reports may significantly underestimate
the potential glycemic benefit of current and future devices, posing challenges
for coverage and reimbursement. We reviewed the potential limitations of the
recent Cochrane Collaboration report on CGM, focusing on the 12 studies that
assessed RT-CGM use in adults, children/adolescents or both.
PMID- 26420627
TI - Effect of nickel titanium file design on the root surface strain and apical
microcracks.
AB - The aim of this study was to determine the effect of nickel titanium file design
on the root surface strain generated and apical microcracks caused during canal
shaping. Thirty-three mandibular incisors were distributed into LightSpeed X,
FlexMaster and a control group. A strain gauge was fixed apically on the proximal
root surface to determine the maximum strain during canal shaping. Except for the
control group, all root canals were enlarged to size 50. Images were taken after
removing the apical 1 and 2 mm of the root end. Mean maximum strain values and
presence of microcracks were statistically compared using the t-test and chi
square test, respectively. During canal shaping, the strain increased
cumulatively with mean maximum strains of 808.2 +/- 228.8 and 525.1 +/- 168.9
microstrain in LightSpeed X and FlexMaster, respectively (P = 0.004). Both
systems caused comparable microcracks. Although LightSpeed X produced higher
maximum strain, no difference in microcrack development was found between both
systems.
PMID- 26420628
TI - Port type is a possible risk factor for implantable venous access port-related
bloodstream infections and no sign of local infection predicts the growth of gram
negative bacilli.
AB - BACKGROUND: Implantable venous access port (IVAP)-related blood stream infections
(BSIs) are one of the most common complications of implantable venous ports. The
risk factors and pathogens for IVAP-related BSIs are still controversial.
METHODS: We retrospectively reviewed all patients who received IVAPs at a
Hospital in Taiwan from January 1, 2011 to June 31, 2014. Two types of venous
port, BardPort(r) 6.6 fr (Bard port) and Autosuture Chemosite(r) 7.5 fr (TYCO
port) were used. All patients with clinically proven venous port-related BSIs
were enrolled. RESULTS: A total of 552 patients were enrolled. There were 34
episodes of IVAP-related BSIs during the study period for a total incidence of
0.177 events/1000 catheter days. Port type (TYCO vs. Bard, HR = 7.105 (95%
confidence interval (CI), 1.688-29.904), p = 0.0075), age > 65 years (HR = 2.320
(95 % CI, 1.179-4.564), p = 0.0148), and lung cancer (HR = 5.807 (95% CI, 2.946
11.447), p < 0.001) were risk factors for port infections. We also found that no
local sign of infection was significantly associated with the growth of gram
negative bacilli (p = 0.031). CONCLUSIONS: TYCO venous ports, age > 65 years, and
lung cancer were all significant risk factors for IVAP-related BSIs, and no sign
of infection was significantly associated with the growth of gram-negative
bacilli.
PMID- 26420630
TI - Theoretical and experimental studies on the performances of barbital-imprinted
systems.
AB - By using density functional theory, we studied the interaction process between
barbital and 2-vinyl-4,6-diamino-1,3,5-triazine in acetonitrile at 333 K.
Barbital and 2-vinyl-4,6-diamino-1,3,5-triazine were used as the template and
functional monomer, respectively. The molecularly imprinted polymer microspheres
containing barbital and 2-vinyl-4,6-diamino-1,3,5-triazine were synthesized
through precipitation polymerization. After removing the template molecule
barbital, the average diameter of the obtained molecularly imprinted polymers was
1.45 MUm. By optimizing the molar ratio of barbital and the 2-vinyl-4,6-diamino
1,3,5-triazine, the resulting molecularly imprinted polymers showed the highest
adsorption for the barbital. The analysis of the Scatchard plot revealed that the
dissociation constant (Kd ) and apparent maximum adsorption quantity (Qmax ) of
the molecularly imprinted polymers were 30.69 mg/L and 8.68 mg/g, respectively.
The study of selective adsorption showed that molecularly imprinted polymers
exhibited higher selectivity for barbtital than that for 1,3-dimethyl barbituric
acid and pentobarbital. Herein, the studies can provide theoretical and
experimental references for the barbital-imprinted system.
PMID- 26420629
TI - Risk of low bone mineral density in patients with rheumatoid arthritis treated
with biologics.
AB - BACKGROUND: Osteoporosis is a complication of rheumatoid arthritis (RA). We
identified risk factors for osteoporosis during treatment with biologics.
METHODS: Femoral neck bone mineral density (BMD) was measured in 186 patients
with biologics-treated RA. We compared the characteristics of those with BMD
>=70% of young adult mean (YAM) and those with BMD <70% of YAM, and undertook
multivariable logistic regression analysis to identify risk factors for bone
loss. RESULTS: Mean age and disease duration, the proportion of females, scores
in the Modified Health Assessment Questionnaire and history of vertebral fracture
were significantly greater in the BMD <70% of YAM group, but body mass index
(BMI) was significantly lower in the BMD <70% of YAM group. There was no
significant difference between the groups in terms of other biomarkers of RA
activity, the proportion treated with methylprednisolone, or the duration or
choice of biologics. The proportions of patients treated with anti-osteoporosis
drugs and parathyroid hormone were significantly higher in the BMD <70% of YAM
group. In the multivariable analysis, advanced age, female, longer disease
duration, history of past thoracic or lumbar vertebral fracture, higher
Steinbrocker classification and lower BMI were significant factors for BMD <70%
of YAM. DISCUSSION: We identified risk factors for bone loss in patients with RA
treated with biologics. Before suppression of disease activity by biologics, bone
loss might already be advanced. CONCLUSIONS: We recommend that patients with RA
who possess these risk factors be considered for earlier and more intense
treatment to prevent bone loss, as well as addressing RA disease progression.
PMID- 26420631
TI - Corrigendum: Unravelling the origin of the giant Zn deficiency in wurtzite type
ZnO nanoparticles.
PMID- 26420632
TI - Cardiac autonomic dysfunction in chronic stroke women is attenuated after
submaximal exercise test, as evaluated by linear and nonlinear analysis.
AB - BACKGROUND: We evaluated cardiac autonomic modulation in women with chronic
ischemic stroke (at least 4 years post-stroke) at rest and in response to
submaximal exercise test. METHODS: Fourteen post-stroke women (S group) and 10
healthy women (C group) participated in this study. Autonomic modulation (using
linear and nonlinear analysis), blood pressure and metabolic variables at rest
were evaluated immediately after the exercise test and during the recovery period
(20 min). All participants underwent submaximal exercise test on cycle ergometer
with gas analysis. RESULTS: At rest, the S group displayed higher lactate
concentration, systolic (SBP) and diastolic blood pressure (DBP) values when
compared to C group. Furthermore, the S group had lower heart rate variability
(HRV) in time domain (SDNN: S = 30 +/- 5 vs. 40 +/- 8 ms; rMSSD: S = 14 +/- 2 vs.
C = 34 +/- 3 ms), decreased high frequency band of pulse interval (S = 8.4 +/- 2
vs. 33.1 +/- 9 %) and 2V pattern of symbolic analysis (S = 17.3 +/- 1 vs. 30 +/-
3 %) (both indicators of cardiac vagal modulation) when compared to C group.
Immediately after exercise, S group presented higher values of lactate, SBP, DBP
and double product when compared to C group, as well as decreased heart rate
recovery (HRR) measured at the first, second and third minutes. At recovery time,
all HRV parameters in time and frequency domains improved in the S group;
however, HF band remained lower when compared to C group. CONCLUSIONS: After the
exercise test, women with chronic stroke presented reduced heart rate
variability, reduced cardiac vagal modulation, as well as reduced HRR, while
displayed an improvement of heart rate variability and cardiac vagal modulation
when compared to their baseline. These results reinforce the importance of a
physically active lifestyle for cardiovascular autonomic disorders observed in
chronic stroke women.
PMID- 26420633
TI - Fluorescence Polarization Based Nucleic Acid Testing for Rapid and Cost-Effective
Diagnosis of Infectious Disease.
AB - A new nucleic acid detection method was developed for a rapid and cost-effective
diagnosis of infectious disease. This approach relies on the three unique
elements: 1) detection probes that regulate DNA polymerase activity in response
to the complementary target DNA; 2) universal reporters conjugated with a single
fluorophore; and 3) fluorescence polarization (FP) detection. As a proof-of
concept, the assay was used to detect and sub-type Salmonella bacteria with
sensitivities down to a single bacterium in less than three hours.
PMID- 26420634
TI - Photoreduction of Hg(ii) and photodemethylation of methylmercury: the key role of
thiol sites on dissolved organic matter.
AB - This study examined the kinetics of photoreduction of Hg(ii) and
photodemethylation of methylmercury (MeHg(+)) attached to, or in the presence of,
dissolved organic matter (DOM). Both Hg(ii) and MeHg(+) are principally bound to
reduced sulfur groups associated with DOM in many freshwater systems. We propose
that a direct photolysis mechanism is plausible for reduction of Hg(ii) bound to
reduced sulfur groups on DOM while an indirect mechanism is supported for
photodemethylation of MeHg(+) bound to DOM. UV spectra of Hg(ii) and MeHg(+)
bound to thiol containing molecules demonstrate that the Hg(ii)-S bond is capable
of absorbing UV-light in the solar spectrum to a much greater extent than MeHg(+)
S bonds. Experiments with chemically distinct DOM isolates suggest that
concentration of DOM matters little in the photochemistry if there are enough
reduced S sites present to strongly bind MeHg(+) and Hg(ii); DOM concentration
does not play a prominent role in photodemethylation other than to screen light,
which was demonstrated in a field experiment in the highly colored St. Louis
River where photodemethylation was not observed at depths >= 10 cm. Experiments
with thiol ligands yielded slower photodegradation rates for MeHg(+) than in
experiments with DOM and thiols; rates in the presence of DOM alone were the
fastest supporting an intra-DOM mechanism. Hg(ii) photoreduction rates, however,
were similar in experiments with only DOM, thiols plus DOM, or only thiols
suggesting a direct photolysis mechanism. Quenching experiments also support the
existence of an intra-DOM photodemethylation mechanism for MeHg(+). Utilizing the
difference in photodemethylation rates measured for MeHg(+) attached to DOM or
thiol ligands, the binding constant for MeHg(+) attached to thiol groups on DOM
was estimated to be 10(16.7).
PMID- 26420636
TI - The effectiveness and safety of treatments used for polycystic ovarian syndrome
management in adolescents: a systematic review and network meta-analysis
protocol.
AB - BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine
disease that is seen among adolescent women. Currently, there is limited evidence
to support treatment options leading to considerable variation in practice among
healthcare specialists. The objective of this study is to review and synthesize
all the available evidence on treatment options for PCOS among adolescent women.
METHODS/DESIGN: We will conduct a systematic review of all randomized controlled
trials evaluating the use of metformin, oral contraceptive pills as monotherapy,
or as combination with pioglitazone, spironolactone, flutamide, and lifestyle
interventions in the treatment of PCOS in adolescent women ages 11 to 19 years.
The primary outcome measures are menstrual regulation and change hirsutism
scores. The secondary outcome measures include acne scores, prevalence of
dysglycaemia, BMI, lipid profile, total testosterone level, and adverse events.
We will perform literature searches through Ovid Medline, Ovid Embase, and
Cochrane Central Register of Controlled Trials (CENTRAL), and gray literature
resources. Two reviewers will independently screen titles and abstracts of
identified citations, review the full texts of potentially eligible trials,
extract information from eligible trials, and assess the risk of bias and quality
of the evidence independently. Results of this review will be summarized
narratively and quantitatively as appropriate. We will perform a multiple
treatment comparison using network meta-analysis to estimate the pooled direct
and indirect effects for all PCOS interventions on outcomes if adequate data is
available. DISCUSSION: PCOS treatment poses a clinical challenge to the patients
and physicians. This is the first systematic review and network meta-analysis for
PCOS treatment in adolescents. We expect that our results will help improve
patient care, unify the treatment approaches among specialists, and encourage
research for other therapeutic options. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
CRD42015016148.
PMID- 26420637
TI - Drug-induced lupus erythematosus associated with donepezil: a case report.
AB - The possibility that drug-induced lupus erythematosus (DILE) can be induced by
donepezil is presented in this clinical case. Donepezil is an inhibitor of
acetylcholinesterase used for the treatment of Alzheimer's disease. It is the
first time that donepezil causes DILE.
PMID- 26420638
TI - Dementia in older people admitted to hospital: a regional multi-hospital
observational study of prevalence, associations and case recognition.
AB - BACKGROUND: Previous studies have indicated a prevalence of dementia in older
admissions of ~42% in a single London teaching hospital, and 21% in four
Queensland hospitals. However, there is a lack of published data from any
European country on the prevalence of dementia across hospitals and between
patient groups. OBJECTIVE: To determine the prevalence and associations of
dementia in older patients admitted to acute hospitals in Ireland. METHODS: Six
hundred and six patients aged >=70 years were recruited on admission to six
hospitals in Cork County. Screening consisted of Standardised Mini-Mental State
Examination (SMMSE); patients with scores <27/30 had further assessment with the
Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Final
expert diagnosis was based on SMMSE, IQCODE and relevant medical and demographic
history. Patients were screened for delirium and depression, and assessed for co
morbidity, functional ability and nutritional status. RESULTS: Of 598 older
patients admitted to acute hospitals, 25% overall had dementia; with 29% in
public hospitals. Prevalence varied between hospitals (P < 0.001); most common in
rural hospitals and acute medical admissions. Only 35.6% of patients with
dementia had a previous diagnosis. Patients with dementia were older and frailer,
with higher co-morbidity, malnutrition and lower functional status (P < 0.001).
Delirium was commonly superimposed on dementia (57%) on admission. CONCLUSION:
Dementia is common in older people admitted to acute hospitals, particularly in
acute medical admissions, and rural hospitals, where services may be less
available. Most dementia is not previously diagnosed, emphasising the necessity
for cognitive assessment in older people on presentation to hospital.
PMID- 26420640
TI - Robotic surgery: It is a better mousetrap.
PMID- 26420641
TI - How to do (or not to do) ... translation of national health accounts data to
evidence for policy making in a low resourced setting.
AB - For more than a decade, the Organization for Economic Co-operation and
Development (OECD), the World Health Organization (WHO) and the World Bank have
promoted the international standardization of National Health Accounts (NHA) for
reporting global statistics on public, private and donor health expenditure and
improve the quality of evidence-based decision-making at country level. A 2010
2012 World Bank review of NHA activity in 50 countries found structural and
technical constraints (rather than cost) were key impediments to
institutionalizing NHA in many low- and middle-income countries (LMICs). Pilot
projects focused resources on data production, neglecting longer-term capacity
building for analysing the data, developing ownership among local stakeholders
and establishing routine production, utilization and dissemination of NHA data.
Hence, genuine institutionalization of NHA in most LMICs has been slow to
materialize. International manuals focus on the production of NHA data and do not
include practical, incremental and low-cost strategies to guide countries in
translating the data into evidence for policy-making. The main aim of this
article is to recommend strategies for bridging this divide between production
and utilization of NHA data in low-resource settings. The article begins by
discussing the origins and purpose of NHA, including factors currently
undermining their uptake. The focus then turns to the development and application
of strategies to assist LMICs in 'unlocking' the hidden value of their NHA. The
article draws on the example of Fiji, a country currently attempting to integrate
their NHA data into policy formulation, despite minimal resources, training and
familiarity with economic analysis of health systems. Simple, low cost
recommendations such as embedding health finance indicators in planning
documents, a user-friendly NHA guide for evaluating local health priorities, and
sharing NHA data for collaborative research have helped translate NHA from raw
data to evidence for policymaking.
PMID- 26420639
TI - Large national series of patients with Xq28 duplication involving MECP2:
Delineation of brain MRI abnormalities in 30 affected patients.
AB - Xq28 duplications encompassing MECP2 have been described in male patients with a
severe neurodevelopmental disorder associated with hypotonia and spasticity,
severe learning disability, stereotyped movements, and recurrent pulmonary
infections. We report on standardized brain magnetic resonance imaging (MRI) data
of 30 affected patients carrying an Xq28 duplication involving MECP2 of various
sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent
malformations and attempt to determine whether variations in imaging features
could be explained by differences in the size of the duplications. We showed that
93% of patients had brain MRI abnormalities such as corpus callosum abnormalities
(n = 20), reduced volume of the white matter (WM) (n = 12), ventricular
dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images
involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5).
The occipitofrontal circumference varied considerably between >+2SD in five
patients and <-2SD in four patients. Among the nine patients with dilatation of
the lateral ventricles, six had a duplication involving L1CAM. The only patient
harboring bilateral posterior subependymal nodular heterotopia also carried an
FLNA gene duplication. We could not demonstrate a correlation between
periventricular WM hyperintensities/delayed myelination and duplication of the
IKBKG gene. We thus conclude that patients with an Xq28 duplication involving
MECP2 share some similar but non-specific brain abnormalities. These imaging
features, therefore, could not constitute a diagnostic clue. The genotype
phenotype correlation failed to demonstrate a relationship between the presence
of nodular heterotopia, ventricular dilatation, WM abnormalities, and the
presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.
PMID- 26420642
TI - Quality at the centre of universal health coverage.
AB - The last decade of the MDG era witnessed substantial focus on reaching the bottom
economic quintiles in low and middle income countries. However, the inordinate
focus on reducing financial risk burden and increasing coverage without
sufficient focus on expanding quality of services may account for slow progress
of the MDGs in many countries. Human Resources for Health underlie quality and
service delivery improvements, yet remains under-addressed in many national
strategies to achieve Universal Health Coverage. Without adequate investments in
improving and expanding health professional education, making and sustaining
gains will be unlikely. The transition from the Millennium Development Goals
(MDG) to the Sustainable Development Goals (SDG), with exciting new financing
initiatives such as the Global Financing Facility brings the potential to enact
substantial gains in the quality of services delivered and upgrading human health
resources. This focus should ensure effective methodologies to improve health
worker competencies and change practice are employed and ineffective and harmful
ones eliminated (including undue influence of commercial interests).
PMID- 26420643
TI - Conformational Memory of a Protein Revealed by Single-Molecule Spectroscopy.
AB - Proteins are supramolecular machines that carry out a wide range of different
functions, many of which require flexibility. Up until now spontaneous
conformational fluctuations of proteins have always been assumed to reflect a
stochastic random process. However, if changing between different conformational
states was random, then it would be difficult to understand how conformational
control of protein function could have evolved. Here we demonstrate that a single
protein can show conformational memory. This is exactly the process that can
facilitate the evolution of control of switching between two conformational
states that can then be used to regulate protein function.
PMID- 26420644
TI - Professional translational research: a new hybrid paradigm in early drug
discovery.
AB - While industry makes cuts to early drug discovery research, the demand for
innovation in the pursuit of novel medicines continues to grow. Who should fill
this gap? Academia clearly is a rich source of innovation but how can new basic
research concepts find their way into industrial application? A new paradigm for
early drug discovery involves professional translational research centers, which
function as facilitators and translators at the academia-industry interface,
harnessing the strengths of both worlds and leveraging the high innovation
potential of academia by using the robustness and efficiency of industry. In this
article, the authors discuss the set-up and essential requirements for the
successful translation of new drug concepts.
PMID- 26420645
TI - Continuous activation of Nrf2 and its target antioxidant enzymes leads to
arsenite-induced malignant transformation of human bronchial epithelial cells.
AB - Long-term exposure to arsenite leads to human lung cancer, but the underlying
mechanisms of carcinogenesis remain obscure. The transcription factor of nuclear
factor-erythroid-2 p45-related factor (Nrf2)-mediated antioxidant response
represents a critical cellular defense mechanism and protection against various
diseases. Paradoxically, emerging data suggest that the constitutive activation
of Nrf2 is associated with cancer development, progression and chemotherapy
resistance. However, the role of Nrf2 in the occurrence of cancer induced by long
term arsenite exposure remains to be fully understood. By establishing
transformed human bronchial epithelial (HBE) cells via chronic low-dose arsenite
treatment, we showed that, in acquiring this malignant phenotype, continuous low
level of ROS and sustained enhancement of Nrf2 and its target antioxidant enzyme
levels were observed in the later-stage of arsenite-induced cell transformation.
The downregulation of Keap1 level may be responsible for the over-activation of
Nrf2 and its target enzymes. To validate these observations, Nrf2 was knocked
down in arsenite-transformed HBE cells by SiRNA transfection, and the levels of
Nrf2 and its target antioxidant enzymes, ROS, cell proliferation, migration, and
colony formation were determined following these treatments. Results showed that
blocked Nrf2 expression significantly reduced Nrf2 and its target antioxidant
enzyme levels, restored ROS levels, and eventually suppressed cell proliferation,
migration, and colony formation of the transformed cells. In summary, the results
of the study strongly suggested that the continuous activation of Nrf2 and its
target antioxidant enzymes led to the over-depletion of intracellular ROS levels,
which contributed to arsenite-induced HBE cell transformation.
PMID- 26420646
TI - The cost-effectiveness of grip on challenging behaviour: an economic evaluation
of a care programme for managing challenging behaviour.
AB - OBJECTIVE: The objective of the study was to evaluate the cost-effectiveness of
implementing the Grip on Challenging Behaviour care programme (GRIP) on dementia
special care units in comparison with usual care. METHODS: A stepped wedge design
was used. Challenging behaviour and quality of life were measured using the Cohen
Mansfield Agitation Inventory (CMAI) and the QUALIDEM. Quality-adjusted life
years (QALYs) were calculated using the EuroQol-5D. Psychoactive medication use
(range 0-5 per measurement) and sick leave were registered. Costs included
medication, time spent on challenging behaviour and education. Costs and effects
were analysed using linear multilevel regression. Incremental cost-effectiveness
ratios were calculated. Statistical uncertainty was estimated using
bootstrapping. RESULTS: Seventeen dementia special care units participated. GRIP
led to improvement on the QUALIDEM subscale social relations (1.6; 95% CI 0.18 to
3.4) and on the use of psychoactive medication (-0.73; 95% CI -1.1 to -0.46) and
to a decrease in QALYs (-0.02; 95% CI -0.06 to -0.003). No significant effects on
CMAI, sick leave and other QUALIDEM subscales were found. The intervention was
not cost-effective in comparison with usual care with regard to CMAI score, QALYs
and sick leave. The willingness to pay should be 320?/point improvement on the
QUALIDEM subscale social relations and 370?/psychoactive medication less to reach
a 0.95 probability of cost-effectiveness. CONCLUSION: It depends on how much
society is willing to pay whether GRIP can be considered cost-effective. Because
the appropriateness of the current methods for analysing cost-effectiveness in
this specific population is uncertain, the positive effects on behaviour,
medication and job satisfactions should also be taken in account in the decision
making.
PMID- 26420647
TI - Targeting danger-associated molecular patterns after myocardial infarction.
AB - INTRODUCTION: Myocardial infarction (MI) provokes an intense inflammatory
response that can lead to left ventricular adverse remodeling and heart failure
(HF). The prognosis of HF patients is poor and related to a decreased quality of
life and considerable health care costs. Hence, targeting the early inflammatory
response after MI provides an interesting target to attenuate left ventricular
remodeling and prevent HF. AREAS COVERED: In the current review, we discuss the
theory that our immune system does not distinguish between self and non-self, but
rather senses danger. So-called danger-associated molecular patterns (DAMPs)
serve as ligands for pattern recognition receptors (PRRs), which act as signal
transduction molecules to induce a pro-inflammatory state. Many different DAMPs
and PRRs have been identified recently. Here, we provide a concise overview of
their interactions as well as their role in the inflammatory response after MI.
EXPERT OPINION: Interference with Toll-like receptor (TLR) 2, TLR4 and NLRP3
inflammasome signaling has consistently shown to reduce infarct size and preserve
cardiac function post-MI in experimental animal models. Since clinically
applicable inhibitors have been developed for these pathways, the path has been
cleared to assess whether these promising results can be translated into the
human situation.
PMID- 26420648
TI - Comparative genomic analysis of human Chlamydia pneumoniae isolates from
respiratory, brain and cardiac tissues.
AB - Chlamydia pneumoniae is an obligate intracellular bacterium implicated in a wide
range of human diseases including atherosclerosis and Alzheimer's disease.
Efforts to understand the relationships between C. pneumoniae detected in these
diseases have been hindered by the availability of sequence data for non
respiratory strains. In this study, we sequenced the whole genomes for C.
pneumoniae isolates from atherosclerosis and Alzheimer's disease, and compared
these to previously published C. pneumoniae genomes. Phylogenetic analyses of
these new C. pneumoniae strains indicate two sub-groups within human C.
pneumoniae, and suggest that both recombination and mutation events have driven
the evolution of human C. pneumoniae. Further fine-detailed analyses of these new
C. pneumoniae sequences show several genetically variable loci. This suggests
that similar strains of C. pneumoniae are found in the brain, lungs and
cardiovascular system and that only minor genetic differences may contribute to
the adaptation of particular strains in human disease.
PMID- 26420649
TI - 'Watching an artist at work': aesthetic leadership in clinical nursing
workplaces.
AB - AIMS AND OBJECTIVES: To explore how clinical leaders enact aesthetic leadership
in clinical nursing workplaces. BACKGROUND: Clinical leadership is heralded as
vital for safe and effective nursing. Different leadership styles have been
applied to the clinical nursing workplace over recent years. Many of these styles
lack an explicit moral dimension, instead focusing on leader qualities and
developing leader competence around team building, quality and safety. Aesthetic
leadership, with its explicit moral dimension, could enhance clinical leadership
effectiveness and improve nursing workplaces. How aesthetic leadership is enacted
in clinical nursing settings requires exploration. DESIGN: A qualitative design,
employing conversation-style interviews with experienced registered nurses and
written responses gathered from an online descriptive survey. METHODS: Narrative
data were gathered from interviews with 12 registered nurses and written accounts
from 31 nurses who responded to an online survey. Together, transcribed interview
data and the written accounts were subject to thematic analysis. RESULTS: Three
main themes emerged: Leading by example: 'be seen in the clinical area'; Leading
with composure: 'a sense of calm in a hideous shift'; and Leading through nursing
values: 'create an environment just by your being'. CONCLUSIONS: Aesthetic
leadership was shown to enhance clinical leadership activities in the nursing
workplace. The capacity for clinical leaders to be self-reflective can positively
influence the nursing workplace. It was apparent that clinical leader
effectiveness can be enhanced with nursing values underpinning leadership
activities and by being a visible, composed role model in the clinical workplace.
RELEVANCE TO CLINICAL PRACTICE: Aesthetic leadership can enhance clinical nursing
workplaces with its explicit moral purpose and strong link to nursing values.
Clinical leaders who incorporate these attributes with being a visible, composed
role model have the capacity to improve the working lives of nurses across a
range of clinical settings.
PMID- 26420655
TI - Shielding Upconversion by Surface Coating: A Study of the Emission Enhancement
Factor.
AB - Surface coating is a commonly used strategy to enhance upconversion emissions by
shielding the luminescent core from surface quenching. In this work, we provide
insights into the effect of surface coating on upconversion by investigating
NaYF4 :Yb/Er nanoparticles and the corresponding NaYF4 :Yb/Er@NaYF4 core-shell
nanoparticles, as a function of dopant concentration of Yb(3+) and excitation
power. We observe declining emission enhancement factors with decreasing Yb(3+)
concentration and increasing excitation power. Our mechanistic investigations
suggest that the phenomenon originates from stepwise excitation in the
upconversion process, as well as energy hopping among the Yb(3+) dopants. This
increased understanding of the effect of surface coating on upconversion should
be important towards the rational design of lanthanide-doped core-shell
nanoparticles for various applications.
PMID- 26420656
TI - Erratum: An assessment of the cost-effectiveness of magnetic resonance, including
diffusion-weighted imaging, in patients with transient ischaemic attack and minor
stroke: a systematic review, meta-analysis and economic evaluation.
PMID- 26420657
TI - A covalent homodimer probing early oligomers along amyloid aggregation.
AB - Early oligomers are crucial in amyloid aggregation; however, due to their
transient nature they are among the least structurally characterized species. We
focused on the amyloidogenic protein beta2-microglobulin (beta2m) whose early
oligomers are still a matter of debate. An intermolecular interaction between D
strands of facing beta2m molecules was repeatedly observed, suggesting that such
interface may be relevant for beta2m dimerization. In this study, by mutating
Ser33 to Cys, and assembling the disulphide-stabilized beta2m homodimer (DimC33),
such DD strand interface was locked. Although the isolated DimC33 display a
stability similar to wt beta2m under native conditions, it shows enhanced amyloid
aggregation propensity. Three distinct crystal structures of DimC33 suggest that
dimerization through the DD interface is instrumental for enhancing DimC33
aggregation propensity. Furthermore, the crystal structure of DimC33 in complex
with the amyloid-specific dye Thioflavin-T pinpoints a second interface, which
likely participates in the first steps of beta2m aggregation. The present data
provide new insight into beta2m early steps of amyloid aggregation.
PMID- 26420658
TI - Surgical excision of ovarian endometriomas: Does it truly impair ovarian reserve?
Long term anti-Mullerian hormone (AMH) changes after surgery.
AB - AIM: The long-term effects of laparoscopic cystectomy on ovarian reserve in
patients with unilateral and bilateral ovarian endometriomas were evaluated.
METHODS: A total of 22 patients undergoing laparoscopic cystectomy for unilateral
endometrioma (n = 10) and bilateral endometriomas (n = 12) were included in the
study. RESULT(S): Serum anti-Mullerian hormone (AMH) levels significantly
decreased from the baseline value (3.98 +/- 3.27 ng/mL) one (1.67 +/- 1.56
ng/mL), three (2.01 +/- 1.70 ng/mL), and six months (2.43 +/- 2.39 ng/mL)
postoperatively. There was no difference between preoperative and 12 month
postoperative AMH levels (4.01 +/- 3.39 ng/mL) (P > 0.05). Patients with
bilateral endometriomas had a significantly higher rate of decline in AMH levels
12 months after surgery than patients with monolateral endometriomas (P = 0.035),
but in both groups there was no difference in AMH levels at one and 12 months
postoperatively (P > 0.05). CONCLUSION(S): AMH levels temporarily decreased after
laparoscopic cystectomy for ovarian endometriomas, with complete recovery of
preoperative AMH values at 12 months postoperatively. This pattern was equal in
patients with bilateral and unilateral ovarian involvement. Patients with
bilateral cysts have higher rates of decline of AMH levels compared to patients
with unilateral affection.
PMID- 26420659
TI - Effect of intra-membrane C60 fullerenes on the modulus of elasticity and the
mechanical resistance of gel and fluid lipid bilayers.
AB - Penetration and partition of C60 to the lipid bilayer core are both relevant to
C60 toxicity, and useful to realise C60 biomedical potential. A key aspect is the
effect of C60 on bilayer mechanical properties. Here, we present an experimental
study on the mechanical effect of the incorporation of C60 into the hydrophobic
core of fluid and gel phase zwitterionic phosphatidylcholine (PC) lipid bilayers.
We demonstrate its incorporation inside the hydrophobic lipid core and the effect
on the packing of the lipids and the vesicle size using a combination of infrared
(IR) spectroscopy, atomic force microscopy (AFM) and laser light scattering.
Using AFM we measured the Young's modulus of elasticity (E) of 1,2-dipalmitoyl-sn
glycero-3-phosphocholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine
(DMPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) in the absence
(presence) of intra-membranous C60 at 24.5 degrees C. E of fluid phase supported
bilayers is not altered by C60, but E increases with incorporation of C60 in gel
phase bilayers. The increase is higher for longer hydrocarbon chains: 1.6 times
for DPPC and 2 times for DSPC. However the mechanical resistance of gel phase
bilayers of curved bilayered structures decreases with the incorporation of C60.
Our combined results indicate that C60 causes a decrease in gel phase lipid
mobility, i.e. an increase in membrane viscosity.
PMID- 26420661
TI - Gene-gene interaction of ATG5, ATG7, BLK and BANK1 in systemic lupus
erythematosus.
AB - AIM: Autophagy-related gene 5 (ATG5), ATG7, B-lymphoid tyrosine kinase (BLK) and
B-cell scaffold protein with ankyrin repeats 1 (BANK1) are involved in B-cell
signaling; several genome-wide association studies detected these genes as
candidates involved in systemic lupus erythematosus (SLE). We aimed to replicate
the association of these genes with SLE in Chinese Han and to search for possible
gene-gene interactions. METHODS: TaqMan single-nucleotide polymorphism (SNP)
genotyping was used to detect rs548234, rs665791 in ATG5, rs11706903 in ATG7,
rs2736340 in BLK and rs10516487 in BANK1 in 382 SLE patients and 660 healthy
controls. The epistasis effect was analyzed by logistic regression, multifactor
dimensionality reduction (MDR) and linear regression analysis. RESULTS: SLE was
associated with frequency of rs548234 (P = 0.010; odds ratio [OR] = 1.298),
rs2736340 (P = 2.47 * 10-5 ; OR = 1.574) and rs10516487 (P = 0.002; OR = 0.642).
Although no epistasis effects were found among three autophagy-related gene loci
or with rs2736340 and rs10516487, BLK and BANK1 had the closest interaction
effect on logistic regression analysis (P = 0.013; OR = 1.205), MDR (P < 0.0001),
and linear regression analysis (P = 0.0017; R2 = 0.1806). The risk genotype TT of
rs2736340 was associated with decreased messenger RNA level of BLK; BLK
transcript level was lower in SLE patients than healthy controls. CONCLUSION: We
confirmed the association of rs548234, rs2736340 and rs10516487 with SLE in
Chinese Han and reinforced our hypothesis of their epistasis effect in regulating
B-cell signaling in SLE.
PMID- 26420662
TI - A pilot before-and-after study of a brief teaching programme for psychiatry
trainees in mentalizing skills.
AB - BACKGROUND AND AIMS: Negative attitudes in clinicians towards people with
personality disorder are common and associated with poor care. National
guidelines recommend developing interventions to improve attitudes. Mentalization
based treatment theory and techniques provide a plausible intervention. We
therefore evaluated the effect of teaching mentalizing skills on clinicians'
attitudes towards personality disorder. METHODS: Pilot before-and-after study of
trainee psychiatrists receiving four teaching sessions in mentalizing skills.
Self-report questionnaires were completed at baseline and post teaching
programme. MAIN OUTCOME MEASURE: Attitudes to Personality Disorder Questionnaire.
SECONDARY MEASURE: Knowledge and Application of Mentalization-based treatment
Questionnaire. RESULTS: Sixteen doctors were recruited with no study drop-out.
Mean Attitudes to Personality Disorder Questionnaire score was superior post
teaching programme versus baseline (135.3 vs. 124.5, standardised mean difference
= 0.72, 95% confidence interval = 0.01 to 1.44). Mean Knowledge and Application
of Mentalization-based treatment Questionnaire score was superior post teaching
programme versus baseline (112.5 vs. 97.1, standardised mean difference = 1.83,
95% confidence interval 0.98 to 2.67). CONCLUSIONS: As expected from a pilot
study, the estimate of effect is imprecise. Within this limitation, our findings
suggest that teaching in mentalizing skills improved attitudes and mentalization
based treatment knowledge to a clinically relevant degree. This has important
implications for patient outcomes and staff development. Our study paves the way
for a full-scale study to provide more precise and robust evidence.
PMID- 26420660
TI - Genetic diversity and evolutionary insights of respiratory syncytial virus A ON1
genotype: global and local transmission dynamics.
AB - Human respiratory syncytial virus (RSV) A ON1 genotype, first detected in 2010 in
Ontario, Canada, has been documented in 21 countries to date. This study
investigated persistence and transmission dynamics of ON1 by grouping 406
randomly selected RSV-positive specimens submitted to Public Health Ontario from
August 2011 to August 2012; RSV-A-positive specimens were genotyped. We
identified 370 RSV-A (181 NA1, 135 NA2, 51 ON1 3 GA5) and 36 RSV-B positive
specimens. We aligned time-stamped second hypervariable region (330 bp) of G-gene
sequence data (global, n = 483; and Ontario, n = 60) to evaluate transmission
dynamics. Global data suggests that the most recent common ancestor of ON1
emerged during the 2008-2009 season. Mean evolutionary rate of the global ON1 was
4.10 * 10(-3) substitutions/site/year (95% BCI 3.1-5.0 * 10(-3)), not
significantly different to that of Ontario ON1. The estimated mean reproductive
number (R0 = ~ 1.01) from global and Ontario sequences showed no significant
difference and implies stability among global RSV-A ON1. This study suggests that
local epidemics exhibit similar underlying evolutionary and epidemiological
dynamics to that of the persistent global RSV-A ON1 population. These findings
underscore the importance of continual molecular surveillance of RSV in order to
gain a better understanding of epidemics.
PMID- 26420664
TI - A Mechanochemically Triggered "Click" Catalyst.
AB - "Click" chemistry represents one of the most powerful approaches for linking
molecules in chemistry and materials science. Triggering this reaction by
mechanical force would enable site- and stress-specific "click" reactions--a
hitherto unreported observation. We introduce the design and realization of a
homogeneous Cu catalyst able to activate through mechanical force when attached
to suitable polymer chains, acting as a lever to transmit the force to the
central catalytic system. Activation of the subsequent copper-catalyzed "click"
reaction (CuAAC) is achieved either by ultrasonication or mechanical pressing of
a polymeric material, using a fluorogenic dye to detect the activation of the
catalyst. Based on an N-heterocyclic copper(I) carbene with attached polymeric
chains of different flexibility, the force is transmitted to the central
catalyst, thereby activating a CuAAC in solution and in the solid state.
PMID- 26420663
TI - Triplet-triplet annihilation upconversion followed by FRET for the red light
activation of a photodissociative ruthenium complex in liposomes.
AB - Upconversion is a promising way to trigger high-energy photochemistry with low
energy photons. However, combining upconversion schemes with non-radiative energy
transfer is challenging because bringing several photochemically active
components in close proximity results in complex multi-component systems where
quenching processes may deactivate the whole assembly. In this work, PEGylated
liposomes were prepared that contained three photoactive components: a porphyrin
dye absorbing red light, a perylene moiety emitting in the blue, and a light
activatable ruthenium prodrug sensitive to blue light. Time-dependent
spectroscopic studies demonstrate that singlet perylene excited states are non
radiatively transferred to the nearby ruthenium complex by Forster resonance
energy transfer (FRET). Under red-light irradiation of the three-component
membranes, triplet-triplet annihilation upconversion (TTA-UC) occurs followed by
FRET, which results in a more efficient activation of the ruthenium prodrug
compared to a physical mixture of two-component upconverting liposomes and
liposomes containing only the ruthenium complex. This work represents a rare
example where TTA-UC and Forster resonance energy transfer are combined to
achieve prodrug activation in the phototherapeutic window.
PMID- 26420665
TI - Frontal metabolic activity contributes to individual differences in vulnerability
toward total sleep deprivation-induced changes in cognitive function.
AB - Substantial individual differences characterize the changes induced by total
sleep deprivation on cognitive functions. Despite some progress having been
achieved, the mechanisms of individual differences in response to total sleep
deprivation have not been clearly elucidated. Cerebral metabolism in the resting
state is among the key physiological processes supporting the daily function of
the brain, and may play an important role in these individual differences. Twenty
two right-handed participants (nine females and 13 males) between 20 and 26 years
old completed a mathematical processing task both in resting wakefulness and
after 24 h of total sleep deprivation. Fluorine-18 fluorodeoxyglucose positron
emission tomography-computed tomography was used to investigate brain metabolism
changes. The mathematical task was performed after the positron emission
tomography scans were completed. Correlation analysis was used to investigate the
correlations between cognitive performance changes and brain metabolism changes.
Large inter-individual differences were found in the throughput changes, but
these inter-individual differences were not associated with baseline or post
deprivation performance levels. Specifically, deterioration of throughput on the
mathematical processing task was significantly correlated with metabolism changes
in the superior frontal medial gyrus. These findings suggested that frontal
metabolic activity contributes to individual differences in waking-induced
impairment of cognitive performance.
PMID- 26420666
TI - Neonatal Irradiation Leads to Persistent Proteome Alterations Involved in
Synaptic Plasticity in the Mouse Hippocampus and Cortex.
AB - Recent epidemiological data indicate that radiation doses as low as those used in
computer tomography may result in long-term neurocognitive side effects. The aim
of this study was to elucidate long-term molecular alterations related to memory
formation in the brain after low and moderate doses of gamma radiation. Female
C57BL/6J mice were irradiated on postnatal day 10 with total body doses of 0.1,
0.5, or 2.0 Gy; the control group was sham-irradiated. The proteome analysis of
hippocampus, cortex, and synaptosomes isolated from these brain regions indicated
changes in ephrin-related, RhoGDI, and axonal guidance signaling. Immunoblotting
and miRNA-quantification demonstrated an imbalance in the synapse morphology
related Rac1-Cofilin pathway and long-term potentiation-related cAMP response
element-binding protein (CREB) signaling. Proteome profiling also showed impaired
oxidative phosphorylation, especially in the synaptic mitochondria. This was
accompanied by an early (4 weeks) reduction of mitochondrial respiration capacity
in the hippocampus. Although the respiratory capacity was restored by 24 weeks,
the number of deregulated mitochondrial complex proteins was increased at this
time. All observed changes were significant at doses of 0.5 and 2.0 Gy but not at
0.1 Gy. This study strongly suggests that ionizing radiation at the neonatal
state triggers persistent proteomic alterations associated with synaptic
impairment.
PMID- 26420667
TI - Evaluation of the POSSUM, p-POSSUM, o-POSSUM, and APACHE II scoring systems in
predicting postoperative mortality and morbidity in gastric cancer patients.
AB - BACKGROUND/OBJECTIVE: Gastric cancer is the fourth most prevalent cancer
worldwide. The ability to accurately predict surgery-related morbidity and
mortality is critical in deciding both the timing of surgery and choice of
surgical procedure. The aim of this study is to compare the POSSUM, p-POSSUM, o
POSSUM, and APACHE II scoring systems for predicting surgical morbidity and
mortality in Chinese gastric cancer patients, as well as to create new scoring
systems to achieve better prediction. METHODS: Data from 612 gastric cancer
patients undergoing gastrectomy between January 2007 and December 2011 were
included in this study. The predictive abilities of the four scoring systems were
compared by examining observed-to-expected (O/E) ratios, the receiver operating
characteristic curve, Student t test, and chi2 test results. RESULTS: The
observed complication rate of 34% (n = 208) did not differ significantly from the
rate of 36.6% (n = 208) predicted by the POSSUM scoring system (O/E ratio =
0.93). The observed mortality rate was 2.9% (n = 18). For predicting mortality,
POSSUM had an O/E ratio of 0.34 as compared with p-POSSUM (O/E ratio = 0.91), o
POSSUM (O/E ratio = 1.26), and APACHE II (O/E ratio = 0.28). CONCLUSION: The
POSSUM scoring system performed well with respect to predicting morbidity risk
following gastric cancer resection. For predicting postoperative mortality, p
POSSUM and o-POSSUM exhibited superior performance relative to POSSUM and APACHE
II.
PMID- 26420668
TI - Spoof localized surface plasmons on ultrathin textured MIM ring resonator with
enhanced resonances.
AB - We numerically demonstrate that spoof localized surface plasmons (LSPs) resonant
modes can be enhanced based on ultrathin corrugated metal-insulator-metal (MIM)
ring resonator. Further enhancement of the LSPs modes has been achieved by
incorporating an efficient and ease-of-integration exciting method. Quality
factors of resonance peaks have become much larger and multipolar resonances
modes can be easily observed on the textured MIM ring resonator excited by a
microstrip line. Experimental results validate the high-efficiency excitation and
resonance enhancements of spoof LSPs modes on the MIM ring resonator in the
microwave frequencies. We have shown that the fabricated resonator is sensitive
to the variation of both the dielectric constant and the thickness of surrounding
materials under test. The spoof plasmonic resonator can be used as key elements
to provide many important device functionalities such as optical communications,
signal processing, and spectral engineering in the plasmonic integration
platform.
PMID- 26420669
TI - Is it worthwhile to screen patients with type 2 diabetes mellitus for subclinical
Cushing's syndrome?
AB - Variable prevalence of subclinical Cushing's syndrome (SCS) has been reported in
patients with type 2 diabetes mellitus (T2DM), making the need for screening in
this population uncertain. It is unknown if this variability is solely due to
study-related methodological differences or a reflection of true differences in
ethnic predisposition. The objective of this study is to explore the prevalence
of SCS in Asian Indian patients with T2DM. In this prospective single center
study conducted in a tertiary care referral center, 993 T2DM outpatients without
any discriminatory clinical features (easy bruising, facial plethora, proximal
muscle weakness, and/or striae) of hypercortisolism underwent an overnight 1 mg
dexamethasone suppression test (ODST). ODST serum cortisol >=1.8 MUg/dl was
considered positive, and those with positive results were subjected to 48 h, 2
mg/day low dose DST (LDDST). A stepwise evaluation for endogenous
hypercortisolism was planned for patients with LDDST serum cortisol >=1.8 MUg/dl.
Patients with positive ODST and negative LDDST were followed up clinically and re
evaluated a year later for the development of clinically evident Cushing's
syndrome (CS). In this largest single center study reported to date, we found 37
out of 993 (3.72%) patients had ODST serum cortisol >=1.8 MUg/dl. None of them
had LDDST cortisol >=1.8 MUg/dl, nor did they develop clinically evident CS over
a follow-up period of 1 year. Specificity of ODST for screening of CS was 96.3%
in our cohort. None of the T2DM outpatients in our cohort had SCS, hence
cautioning against routine biochemical screening for SCS in this cohort. We
suggest screening be based on clinical suspicion only.
PMID- 26420670
TI - Recombinant expression of a functional myo-inositol-1-phosphate synthase (MIPS)
in Mycobacterium smegmatis.
AB - Myo-inositol-1-phosphate synthase (MIPS, E.C. 5.5.1.4) catalyzes the first step
in inositol production-the conversion of glucose-6-phosphate (Glc-6P) to myo
inositol-1-phosphate. While the three dimensional structure of MIPS from
Mycobacterium tuberculosis has been solved, biochemical studies examining the in
vitro activity have not been reported to date. Herein we report the in vitro
activity of mycobacterial MIPS expressed in E. coli and Mycobacterium smegmatis.
Recombinant expression in E. coli yields a soluble protein capable of binding the
NAD(+) cofactor; however, it has no significant activity with the Glc-6P
substrate. In contrast, recombinant expression in M. smegmatis mc(2)4517 yields a
functionally active protein. Examination of structural data suggests that MtMIPS
expressed in E. coli adopts a fold that is missing a key helix containing two
critical (conserved) Lys side chains, which likely explains the inability of the
E. coli expressed protein to bind and turnover the Glc-6P substrate. Recombinant
expression in M. smegmatis may yield a protein that adopts a fold in which this
key helix is formed enabling proper positioning of important side chains, thereby
allowing for Glc-6P substrate binding and turnover. Detailed mechanistic studies
may be feasible following optimization of the recombinant MIPS expression
protocol in M. smegmatis.
PMID- 26420671
TI - See One, Do One, Order One: a study protocol for cluster randomized controlled
trial testing three strategies for implementing motivational interviewing on
medical inpatient units.
AB - BACKGROUND: General medical hospitals provide care for a disproportionate share
of patients who abuse or are dependent upon substances. This group is among the
most costly to treat and has the poorest medical and addiction recovery outcomes.
Hospitalization provides a unique opportunity to identify and motivate patients
to address their substance use problems in that patients are accessible, have
time for an intervention, and are often admitted for complications related to
substance use that renders hospitalization a "teachable moment." METHODS/DESIGN:
This randomized controlled trial will examine the effectiveness of three
different strategies for integrating motivational interviewing (MI) into the
practice of providers working within a general medical inpatient hospitalist
service: (1) a continuing medical education workshop that provides background and
"shows" providers how to conduct MI (See One); (2) an apprenticeship model
involving workshop training plus live supervision of bedside practice (Do One);
and (3) ordering MI from the psychiatry consultation-liaison (CL) service after
learning about it in a workshop (Order One). Thirty providers (physicians,
physician assistants, nurses) will be randomized to conditions and then assessed
for their provision of MI to 40 study-eligible inpatients. The primary aims of
the study are to assess (1) the utilization of MI in each condition; (2) the
integrity of MI when providers use it on the medical units; and (3) the relative
costs and cost-effectiveness of the three different implementation strategies.
DISCUSSION: If implementation of Do One and Order One is successful, the field
will have two alternative strategies for supporting medical providers' proficient
use of brief behavioral interventions, such as MI, for medical inpatients who use
substances problematically. TRIAL REGISTRATION: Clinical Trials.gov ( NCT01825057
).
PMID- 26420672
TI - Crisis Reliability Indicators Supporting Emergency Services (CRISES): A Framework
for Developing Performance Measures for Behavioral Health Crisis and Psychiatric
Emergency Programs.
AB - Crisis and emergency psychiatric services are an integral part of the healthcare
system, yet there are no standardized measures for programs providing these
services. We developed the Crisis Reliability Indicators Supporting Emergency
Services (CRISES) framework to create measures that inform internal performance
improvement initiatives and allow comparison across programs. The framework
consists of two components-the CRISES domains (timely, safe, accessible, least
restrictive, effective, consumer/family centered, and partnership) and the
measures supporting each domain. The CRISES framework provides a foundation for
development of standardized measures for the crisis field. This will become
increasingly important as pay-for-performance initiatives expand with healthcare
reform.
PMID- 26420674
TI - IMPAIRED FERTILITY AND PERCEIVED DIFFICULTIES CONCEIVING IN GHANA: MEASUREMENT
PROBLEMS AND PROSPECTS.
AB - What is the most appropriate measure of impaired fertility for understanding its
social consequences in sub-Saharan Africa? The dearth of subjective measures in
surveys in the region has prevented comparisons of subjective and objective
measures. Perceived difficulties conceiving may have a greater impact than
objective measures for social outcomes such as divorce, stigmatization and
distress. This study compares 12- (clinical) and 24- (epidemiological) month
measures from biomedicine and 5- and 7-year measures from demography with a
subjective measure of impaired fertility using correlations, random effects
models and test-retest models to assess relationships between measures, their
association with sociodemographic characteristics and the stability of measures
across time. Secondary panel data (1998-2004) from 1350 Ghanaian women aged 15-49
of all marital statuses are used. Longer waiting times to identification of
impaired fertility required by demographic measures result in more stable
measures, but perceived difficulties conceiving are most closely aligned with
clinical infertility (r=0.61; p<0.05). Epidemiological infertility is also
closely aligned with the subjective measure. A large proportion of those
identified as having impaired fertility based purely on waiting times are
successful contraceptors. Where subjective measures are not available,
epidemiological (24-month) measures may be most appropriate for studies of the
social consequences of impaired fertility. Accounting for contraceptive use is
important in order to avoid false positives. Future research should consider a
variety of measures of perceived difficulties conceiving and self-identified
infertility to assess which is most valid; in order to accomplish this, it is
imperative that subjective measures of infertility be included in social surveys
in sub-Saharan Africa.
PMID- 26420673
TI - Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated
genome stability and carcinogenesis.
AB - KLF4 is an important regulator of cell-fate decision, including DNA damage
response and apoptosis. We identify a novel interplay between protein
modifications in regulating KLF4 function. Here we show that arginine methylation
of KLF4 by PRMT5 inhibits KLF4 ubiquitylation by VHL and thereby reduces KLF4
turnover, resulting in the elevation of KLF4 protein levels concomitant with
increased transcription of KLF4-dependent p21 and reduced expression of KLF4
repressed Bax. Structure-based modelling and simulations provide insight into the
molecular mechanisms of KLF4 recognition and catalysis by PRMT5. Following
genotoxic stress, disruption of PRMT5-mediated KLF4 methylation leads to
abrogation of KLF4 accumulation, which, in turn, attenuates cell cycle arrest.
Mutating KLF4 methylation sites suppresses breast tumour initiation and
progression, and immunohistochemical stain shows increased levels of both KLF4
and PRMT5 in breast cancer tissues. Taken together, our results point to a
critical role for aberrant KLF4 regulation by PRMT5 in genome stability and
breast carcinogenesis.
PMID- 26420675
TI - Target-Catalyzed DNA Four-Way Junctions for CRET Imaging of MicroRNA,
Concatenated Logic Operations, and Self-Assembly of DNA Nanohydrogels for
Targeted Drug Delivery.
AB - Here we report a target-catalyzed DNA four-way junction (DNA-4WJ) on the basis of
toehold-mediated DNA strand displacement reaction (TM-SDR), which is readily
applied in enzyme-free amplified chemiluminescence resonance energy transfer
(CRET) imaging of microRNA. In this system, the introduction of target microRNA
let-7a (miR-let-7a) activates a cascade of assembly steps with four DNA hairpins,
followed by a disassembly step in which the target microRNA is displaced and
released from DNA-4WJ to catalyze the self-assembly of additional branched
junctions. As a result, G-quadruplex subunit sequences and fluorophore
fluorescein amidite (FAM) are encoded in DNA-4WJ in a close proximity,
stimulating a CRET process in the presence of hemin/K(+) to form horseradish
peroxidase (HRP)-mimicking DNAzyme that catalyzes the generation of luminol/H2O2
chemiluminescence (CL), which further transfers to FAM. The background signal is
easily reduced using magnetic graphene oxide (MGO) to remove unreacted species
through magnetic separation, which makes a great contribution to improve the
detection sensitivity and achieves a detection limit as low as 6.9 fM microRNA
let-7a (miR-let-7a). In addition, four-input concatenated logic circuits with an
automatic reset function have been successfully constructed relying on the
architecture of the proposed DNA-4WJ. More importantly, DNA nanohydrogels are
self-assembled using DNA-4WJs as building units after centrifugation, which are
driven by liquid crystallization and dense packaging of building units. Moreover,
the DNA nanohydrogels are readily functionalized by incorporating with aptamers,
bioimaging agents, and drug loading sites, which thus are served as efficient
nanocarriers for targeted drug delivery and cancer therapy with high loading
capacity and excellent biocompatibility.
PMID- 26420676
TI - [Impact of learning curve in renal transplantation].
AB - OBJECTIVES: Renal transplantation is performed only in university hospital
centres, in accredited transplanting centres. The aim of this study is to analyse
the learning curve of this operation and its impact on the graft survival.
PATIENTS-METHODS: Monocentric retrospective study in which 3 groups have been
defined: Juniors 1, Juniors 2 and Seniors corresponding respectively to the first
thirty transplantations and to the last thirty transplantations of 5 clinical
leaders, and 30 transplantation graft of referent seniors. Data have been
registered in a database. Operation times, lukewarm ischemic times and
postoperative complications have been compared within the 3 groups. RESULTS: A
clear difference of operation time has been noted within the 3 groups with an
average time of 202 minutes for Juniors 1, 173 minutes for Juniors 2 and 140
minutes for Seniors (P<0.0001). Likewise, concerning lukewarm ischemic time and
vascular anastomosis time respectively with an average time of 72, 59 and 40 min
(P<0.0001). Vascular complications occurred in 20% of cases in Juniors 1, 44.3%
of cases in Juniors 2 and 17% of cases in Seniors (P=0.65). There were no
significant differences of survival without urinary complications: 20% of
complications for Juniors 1, 10% for Juniors 2 and 17% for Seniors (P=0.63).
Similarly results have been obtained with analysing complications following
Clavien's order. CONCLUSION: This study reveals that renal transplantations
operated by young surgeons require longer operation and lukeward ischemic time
but without significant repercussions on the surgical complication rate and the
global survival. This stresses on the importance of surgical training during
medicine internship.
PMID- 26420677
TI - [Neoadjuvant chemotherapy with MVAC in bladder carcinoma: Is the feasibility
really established? Of: Benadiba et al.: Neoadjuvant chemotherapy in muscular
invasive bladder cancer: Complications and consequences on cystectomy, Pr Urol
2015; 25: 549-554].
PMID- 26420678
TI - Efficacy and safety of nicotinamide in the management of hyperphosphatemia in
pediatric patients on regular hemodialysis.
AB - BACKGROUND: Hyperphosphatemia is a common problem in patients with end-stage
renal disease (ESRD) who are on maintenance hemodialysis (HD) and contributes to
the development of secondary hyperparathyroidism and cardiovascular
complications. Nicotinamide (NAM) has been shown in some studies to inhibit
intestinal and renal sodium/phosphorus co-transporters and reduce serum
phosphorus levels. We have therefore evaluated the efficacy and safety of NAM as
adjunctive therapy to calcium-based phosphate binders to control
hyperphosphatemia in hemodialysis patients. METHODS: Sixty pediatric HD
outpatients were randomly divided into two equally sized groups (30 children
each). One group received calcium-based phosphate binder (control group), and the
other received both the calcium-based phosphate binder + NAM at a dose of 100 mg
twice or three times daily (nicotinamide group). Both groups were followed for a
6-month period. RESULTS: Over the 6-month treatment period, children in the NAM
group showed a significant decline in the levels of serum phosphorus (p =
0.0001), serum calcium-phosphorus (Ca * P; p = 0.0001) product and parathyroid
hormone (p = 0.02) versus baseline values and those of the control group. After 6
months of NAM treatment, the mean serum high-density lipoprotein cholesterol
levels had increased significantly (p = 0.01), and the median serum triglyceride
levels had decreased (p = 0.009). There was no significant change in any of these
parameters among the children of the control group. The major adverse events
associated with the NAM therapy were diarrhea, flushing and nausea. CONCLUSION:
The addition of NAM to therapy with phosphate binders is effective in lowering
phosphorus levels and has a beneficial effect on the lipid profile with only mild
side effects.
PMID- 26420680
TI - Effective use of the TSPY gene-specific copy number in determining fetal DNA in
the maternal blood of cynomolgus monkeys.
AB - Since the available concentration of single-copy fetal genes in maternal blood
DNA is sometimes lower than detection limits by PCR methods, the development of
specific and quantitative PCR detection methods for fetal DNA in maternal blood
is anticipated, which may broaden the methods that can be used to monitor
pregnancy. We used the TaqMan qPCR amplification for DYS14 multi-copy sequence
and the SRY gene in maternal blood plasma (cell-free DNA) and fractional
precipitated blood cells (cellular DNA) from individual cynomolgus monkeys at 22
weeks of pregnancy. The availability of cell-free fetal DNA was higher in
maternal blood plasma than that of cellular DNA from fractional precipitated
blood cells. There was a significantly higher (P < 0.001) mean copy number of
fetal male DYS14 from maternal plasma (4.4 * 10(4) copies/mL) than that of
detected fetal cellular DNA from fractional blood cell pellets. The sensitivity
of the DYS14 PCR assay was found to be higher than that of the SRY assay for the
detection of fetal DNA when its presence was at a minimum. The DYS14 assay is an
improved method for quantifying male fetal DNA in circulating maternal blood in
the primate model.
PMID- 26420679
TI - Gender and obesity modify the impact of salt intake on blood pressure in
children.
AB - BACKGROUND: Most modifiable risk factors for high blood pressure (BP), such as
obesity and salt intake, are imprinted in childhood and persist into adulthood.
The aim of our study was to evaluate the intake of salt in children and to assess
its impact on BP taking into account gender and nutritional status. METHODS: A
total of 298 children aged 8-9 years were evaluated in a cross-sectional study.
Anthropometric measurements and 24-h ambulatory monitoring were performed, and
salt intake was determined by 24-h urinary sodium excretion. RESULTS: The average
estimated salt intake among the entire cohort of children enrolled in the study
was 6.5 +/- 2.2 g/day, and it was significantly higher in boys than in girls (6.8
+/- 2.4 vs. 6.1 +/- 1.9 g/day, respectively; p = 0.018) and in overweight/obese
children than in normal weight children (6.8 +/- 2.4 vs. 6.1 +/- 2.0 g/day,
respectively; p = 0.006). Salt intake exceeded the upper limit of the US Dietary
Reference Intake in 72% of children. Daytime systolic BP increased by 1.00 mmHg
(95% confidence interval 0.40-1.59) per gram of daily salt intake in
overweight/obese boys, but not in normal weight boys or in girls. CONCLUSIONS:
Our results demonstrate an extremely high salt intake among 8- to 9-year-old
Portuguese children. Higher salt intake was associated with higher systolic BP in
boys, specifically in those who were overweight/obese. Longitudinal studies are
needed to further evaluate the causal relationship between obesity and high BP
and the mechanism by which salt intake modulates this relationship. Nonetheless,
based on our results, we urge that dietary salt reduction interventions, along
with measures to fight the global epidemic of obesity, be implemented as early in
life as possible.
PMID- 26420681
TI - [Diabetic maculopathy].
AB - Diabetic maculopathy is the result of multifactorial and complex alterations of
the retinal capillaries in association with diabetes mellitus and is divided into
two forms, ischemic maculopathy and diabetic macular edema. Diabetic macular
edema is the leading cause of blindness among people of working age. The
functional and morphological results of intravitreal pharmacotherapy in cases of
fovea-involving macular edema using vascular endothelial growth factor (VEGF)
inhibitors such as ranibizumab and aflibercept obtained in large randomized
clinical trials are excellent and are superior to results obtained with focal or
grid laser coagulation alone. Steroids including dexamethasone and fluocinolone
implants represent approved alternatives, although flucinolone is considered a
second-line therapy in refractory and chronic cases. VEGF inhibitors can be used
in different treatment strategies such as PRN and treat and extend strategies.
Focal laser photocoagulation remains the gold standard for macular edema not
involving the fovea (and therefore usually good visual acuity). Laser is also
still indicated as a panretinal photocoagulation of peripheral retinal ischemic
areas in order to prevent neovascular complications. It remains to be proven
whether panretinal photocoagulation can have an effect on the treatment intervals
of intravitreal pharmacotherapy, too. Surgical treatments such as vitrectomy are
today limited to cases of macular edema with concomitant obvious tractional
pathologies at the vitreoretinal interface.
PMID- 26420683
TI - Different modes of synergistic toxicities between metam/copper (II) and
metam/zinc (II) in HepG2 cells: apoptosis vs. necrosis.
AB - Both metam sodium and copper/zinc-containing compounds are widely used as
fungicides. They therefore may co-occur in the biosphere. Despite certain studies
of individual toxicity for either metam or copper (II)/zinc (II), their
synergistic toxicity has not been examined. In this paper, a remarkable
synergistic toxicity was observed in HepG2 cells when metam and copper (II)/zinc
(II) at non-toxic and sub-toxic levels were combined. Unexpectedly, cell death
modes between metam/copper (II) and metam/zinc (II) were different: For
metam/copper (II), apoptosis was evident from morphological characteristics
including cytoplasm-chromatin condensation, phosphatidylserine (PS) exposure,
SubG0 /G1 DNA fragmentation, mitochondrial membrane potential decrease, pro/anti
apoptotic protein activation, and cytochrome c release; for metam/zinc (II),
necrosis was evident from organelle swelling and uncontrolled collapse. To our
knowledge, this work first not only demonstrates the synergistic toxicities of
metam and both copper (II)/zinc (II), but also verifies the different modes of
apoptosis/necrosis between metam/copper (II) and metam/zinc (II). (c) 2015 Wiley
Periodicals, Inc. Environ Toxicol 31: 1964-1973, 2016.
PMID- 26420682
TI - The evolution of reduced antagonism--A role for host-parasite coevolution.
AB - Why do some host-parasite interactions become less antagonistic over evolutionary
time? Vertical transmission can select for reduced antagonism. Vertical
transmission also promotes coevolution between hosts and parasites. Therefore, we
hypothesized that coevolution itself may underlie transitions to reduced
antagonism. To test the coevolution hypothesis, we selected for reduced
antagonism between the host Caenorhabditis elegans and its parasite Serratia
marcescens. This parasite is horizontally transmitted, which allowed us to study
coevolution independently of vertical transmission. After 20 generations, we
observed a response to selection when coevolution was possible: reduced
antagonism evolved in the copassaged treatment. Reduced antagonism, however, did
not evolve when hosts or parasites were independently selected without
coevolution. In addition, we found strong local adaptation for reduced antagonism
between replicate host/parasite lines in the copassaged treatment. Taken
together, these results strongly suggest that coevolution was critical to the
rapid evolution of reduced antagonism.
PMID- 26420685
TI - Shaping ability of ProTaper NEXT, ProTaper Universal and iRace files in simulated
S-shaped canals.
AB - The aim of this study was to determine the shaping ability of three nickel
titanium endodontic file systems by comparing three parameters: canal deviation,
apical foramen position and instrumentation time. A glide path was established in
30 simulated S-shaped canal blocks that were randomly assigned into three groups
(n = 10): ProTaper Universal, ProTaper NEXT and iRace. Each group was
instrumented per its manufacturer's directions. Pre- and postoperative images
were superimposed to determine any canal deviation or change in apical foramen
position. The instrumentation times were recorded. The iRace system resulted in
the least mean canal deviation. The apical foramen position was least shifted by
the iRace system. The iRace system also required the least instrumentation time.
The iRace system demonstrated the most favourable shaping ability in all three
parameters.
PMID- 26420684
TI - Serum survivin predicts responses to treatment in active rheumatoid arthritis: a
post hoc analysis from the SWEFOT trial.
AB - BACKGROUND: The identification of biomarkers that predict optimal and individual
choices of treatment for patients with rheumatoid arthritis gains increasing
attention. The purpose of this study was to investigate if the proto-oncogene
survivin might aid in treatment decisions in early rheumatoid arthritis. METHODS:
Serum survivin levels were measured in 302 patients who completed the Swedish
pharmacotherapy (SWEFOT) trial at baseline, 3, 12, and 24 months. Survivin levels
> 0.45 ng/mL were considered positive. Based on the survivin status, core set
outcomes measuring disease activity, functional disability, as well as global
health and pain were evaluated after methotrexate (MTX) monotherapy at 3 months,
and at 12 and 24 months of follow-up. Treatment of non-responders was randomly
intensified with either a combination of disease-modifying antirheumatic drugs
(triple therapy: MTX, sulfasalazine, and hydroxychloroquine) or by adding
antibodies against tumor necrosis factor (anti-TNF). RESULTS: Antirheumatic
treatment resulted in an overall decrease of serum survivin levels. Survivin
positive patients at baseline who initially responded to MTX had a higher risk of
disease re-activation (OR 3.21 (95% CI 1.12-9.24), P = 0.032) and failed to
improve in their functional disability (P = 0.018) if having continued on MTX
monotherapy compared to survivin-negative patients. Ever-smokers who were
survivin-positive were less likely to respond to MTX than those who were survivin
negative (OR 1.91 (1.01-3.62), P = 0.045). In survivin-positive patients, triple
therapy led to better improvements in disease activity than did MTX + anti-TNF.
At 24 months, survivin-positive patients randomized to anti-TNF had a higher risk
of active disease than those randomized to triple therapy (OR 3.15 (1.09-9.10), P
= 0.037). DISCUSSION: We demonstrate for the first time that survivin is a
valuable serologic marker that can distinguish drug-specific clinical responses
in early rheumatoid arthritis through the pragmatic clinical setting of the care
based SWEFOT trial. Although treatment response cannot solely be attributable to
survivin status, per protocol sensitivity analyses confirmed the superior effect
of triple therapy on survivin-positive patients. CONCLUSIONS: Survivin-positive
patients have poor outcomes if treated with MTX monotherapy. A decrease of
survivin levels during treatment is associated with better clinical responses.
For survivin-positive patients who fail MTX, triple therapy is associated with
better outcomes than anti-TNF therapy. TRIAL REGISTRATION: WHO database at the
Karolinska University Hospital: CT20080004 ; ClinicalTrials.gov: NCT00764725,
registered 1 October 2008.
PMID- 26420686
TI - Supraclavicular skin temperature and BAT activity in lean healthy adults.
AB - The 'gold standard' for measuring brown adipose tissue (BAT) in humans is
[(18)F]FDG-PET/CT-imaging. With this technique subjects are exposed to ionizing
radiation and are therefore limited in the number of scans that can be performed.
We investigated the relation between supraclavicular skin temperatures and BAT
activity values using a strictly temperature-controlled air-cooling protocol.
Data of 36 male subjects was analyzed. BAT activity was evaluated by [(18)F]FDG
PET/CT-imaging and skin temperature was measured by means of wireless temperature
sensors. Supraclavicular skin temperature dropped less compared to skin
temperatures at other sites (all P values <0.01). A significant positive
correlation was found between the change in supraclavicular skin temperature with
BAT activity (R (2) 0.23), and the change in supraclavicular skin temperature and
non-shivering thermogenesis (R (2) 0.18, both P values <0.01). The correlations
indicate that supraclavicular skin temperature (changes) can potentially be used
as a qualitative measure of BAT activity and BAT thermogenesis.
PMID- 26420689
TI - Mycobacterium angelicum sp. nov., a non-chromogenic, slow-growing species
isolated from fish and related to Mycobacterium szulgai.
AB - The name 'Mycobacterium angelicum' dates back to 2003 when it was suggested for a
slowly growing mycobacterium isolated from freshwater angelfish. This name is
revived here and the novel species is proposed on the basis of the polyphasic
characterization of four strains including the original one. The four strains
presented 100 % 16S rRNA gene sequence similarity with Mycobacterium szulgai but
clearly differed from M. szulgai for the milky white aspect of the colonies. The
sequence similarity with the type strain of M. szulgai ranged, in eight
additionally investigated genetic targets, from 78.9 to 94.3 %, an evident
contrast with the close relatedness that emerged at the level of 16S rRNA gene.
The average nucleotide identity between the genomes of M. szulgai DSM 44166T and
strain 126/5/03T (type strain of the novel species) was 92.92 %, and supported
the status of independent species. The confirmation of the name Mycobacterium
angelicum sp. nov. is proposed, with strain 126/5/03T ( = CIP 109313T = DSM
45057T) as the type strain.
PMID- 26420688
TI - Dicalcin, a zona pellucida protein that regulates fertilization competence of the
egg coat in Xenopus laevis.
AB - Fertilization is a highly coordinated process whereby sperm interact with the egg
coating envelope (called the zona pellucida, ZP) in a taxon-restricted manner,
Fertilization triggers the resumption of the cell cycle of the egg, ultimately
leading to generation of a new organism that contains hereditary information of
the parents. The complete sperm-ZP interaction comprises sperm recognition of the
ZP, the acrosome reaction, penetration of the ZP, and fusion with the egg. Recent
evidence suggests that these processes involve oligosaccharides associated with a
ZP constituent (termed ZP protein), the polypeptide backbone of a ZP protein,
and/or the proper three-dimensional filamentous structure of the ZP. However, a
detailed description of the molecular mechanisms involved in sperm-ZP interaction
remains elusive. Recently, I found that dicalcin, a novel ZP protein-associated
protein, suppresses fertilization through its association with gp41, the frog
counterpart of the mammalian ZPC protein. This review focuses on molecular
aspects of sperm-ZP interaction and describes the fertilization-suppressive
function of dicalcin and associated molecular mechanisms. The amount of dicalcin
in the ZP significantly correlates with alteration of the lectin-staining pattern
within the ZP and the orientation pattern of ZP filaments, which may assist in
elucidating the complex molecular mechanisms that underlie sperm-ZP interaction.
PMID- 26420690
TI - Accuracy of optical coherence tomography (OCT) in pachymetry for glaucoma
patients.
AB - BACKGROUND: Central corneal thickness (CCT) measurement has become an important
test in the diagnosis and management of glaucoma. Currently, ultrasound corneal
thickness measurement (pachymetry) is the most frequently used clinical technique
and the gold standard to assess CCT. Newer instruments are currently available
including the optical coherence tomography (OCT) instrument. The aim of the
present study was therefore to evaluate the accuracy of the CCT measurements
performed by three different observers, both with the OCT and ultrasound
pachymetry (USP), in patients suffering from glaucoma. METHODS: Patients who had
been previously diagnosed with glaucoma participated in this cross-sectional
study. Glaucoma was defined as patients who had at least two repeatable Humphrey
visual fields showing glaucoma damage using the software 24-2, and with the optic
nerve showing typical glaucoma damage. The patients CCTs were measured with OCT
and USP by three different examiners. RESULTS: Seventy eyes of 35 patients were
included. The average age was 74 +/- standard deviation (SD) 10.88, the average
pachymetry value with OCT was 536 +/- 29 MUm, and the average pachymetry with USP
was 532 +/- 32 MUm. The differences between OCT and USP were not significant (t
test, p = 0.32). The intraclass correlation coefficients were, for OCT, 0.99
[confidence interval (CI): 0.98-0.996], and for USP, 0.97 (CI: 0.95-0.98).
CONCLUSIONS: Agreement among the three observers using OCT or USP for pachymetry
measurements was good. OCT might be used as an alternative method for pachymetry
in glaucoma patients.
PMID- 26420687
TI - Frontier studies on fatigue, autonomic nerve dysfunction, and sleep-rhythm
disorder.
AB - Fatigue is defined as a condition or phenomenon of decreased ability and
efficiency of mental and/or physical activities, caused by excessive mental or
physical activities, diseases, or syndromes. It is often accompanied by a
peculiar sense of discomfort, a desire to rest, and reduced motivation, referred
to as fatigue sensation. Acute fatigue is a normal condition or phenomenon that
disappears after a period of rest; in contrast, chronic fatigue, lasting at least
6 months, does not disappear after ordinary rest. Chronic fatigue impairs
activities and contributes to various medical conditions, such as cardiovascular
disease, epileptic seizures, and death. In addition, many people complain of
chronic fatigue. For example, in Japan, more than one third of the general adult
population complains of chronic fatigue. It would thus be of great value to
clarify the mechanisms underlying chronic fatigue and to develop efficient
treatment methods to overcome it. Here, we review data primarily from behavioral,
electrophysiological, and neuroimaging experiments related to neural dysfunction
as well as autonomic nervous system, sleep, and circadian rhythm disorders in
fatigue. These data provide new perspectives on the mechanisms underlying chronic
fatigue and on overcoming it.
PMID- 26420691
TI - Ingested cylindrical batteries in an incarcerated male: a caustic tale!
AB - A 37-year-old incarcerated man presented to the accident and emergency department
following the deliberate ingestion of eight cylindrical batteries. He also
admitted to inserting a razor blade wrapped in cling-film into his rectum; in
addition, he sustained a self-inflicted laceration to his left antecubital fossa,
using the metal casing from a battery. His medical history included a borderline
and emotionally unstable personality disorder. He had ingested several batteries
12 months previously and required an emergency laparotomy to retrieve them. On
the present admission, as there was no clinical evidence of small bowel
obstruction, he was treated conservatively with serial radiographs. Following
conservative management, the batteries failed to progress through the
gastrointestinal tract, hence a laparotomy was performed and all the batteries
were extricated. This paper discusses the management and associated sequelae of
patients presenting following the intentional ingestion of a battery.
PMID- 26420692
TI - Intussusception in gestational choriocarcinoma (not histologically proven),
resolving spontaneously with chemotherapy.
AB - We present a rare case of advanced gestational choriocarcinoma with small bowel
metastatic involvement and intussusception, which presented acutely as a lower
gastrointestinal bleed with symptomatic anaemia and haemoglobin 3.8 g/dL in a
young woman. A diagnosis of gestational choriocarcinoma was made without biopsy,
using a combination of clinical history, isolated elevated human chorionic
gonadotropin markers of 77,000 IU/mL and radiological findings. Surgical
intervention was too high risk due to the presence of active bleeding and
increased vascularity surrounding the intussusception. Owing to the highly
responsive nature of gestational choriocarcinoma to chemotherapy, frontline
chemotherapy alone was used to reduce the size of the metastatic small bowel
deposits, with subsequent resolution of the bleeding and intussusception. This is
the first time chemotherapy alone has been used to successfully resolve small
bowel intussusception secondary to metastatic choriocarcinoma that has been
documented according to PubMed searches.
PMID- 26420693
TI - Lens coloboma treated with lens surgery.
AB - A 5-year-old boy was referred to our clinic due to an abnormal visual acuity test
at school. His corrected visual acuity was counting fingers in the left eye. A
nasal side deficiency of the lens substituted by a membrane was found. Lens
coloboma was diagnosed. After making a 3 mm limbal incision, the colobomatous
lens was removed by anterior continuous curvilinear capsulorhexis and lens
aspiration. Posterior capsulorhexis and anterior vitrectomy on the side of the
lens was performed to prevent posterior capsular or anterior hyaloid opacity. As
the defect in the lens was very large, intracapsular placement of an intraocular
lens was not feasible. A three-piece acrylic soft intraocular lens was placed in
the ciliary sulcus. Since amblyopia was diagnosed by poor corrected visual acuity
as 20/800 1 month after the operation, occlusion therapy with correcting
eyeglasses was started at 6 h a day on the contralateral eye. The patient's
corrected visual acuity improved to 20/125 7 months after the operation.
PMID- 26420694
TI - Pott's puffy tumour: a forgotten diagnosis.
PMID- 26420695
TI - Endoscopic closure of a refractory gastrocutaneous fistula using a novel over-the
scope Padlock clip following de-epithelialisation of the fistula tract.
AB - Persistent gastrocutaneous fistula (GCF) is a difficult to manage complication
following gastrostomy tube removal, with leakage resulting in distressing
sequelae including cutaneous injury, infection and dehydration. Many such
patients are high-risk for invasive surgery and, to date, endoscopic closure
techniques, including clipping systems, have limitations. We present the case of
a 62-year-old woman with persistently leaking GCF 6 months postgastrostomy tube
removal, despite maximal antisecretory therapy and postpyloric feeding, and
describe failed attempted endoscopic closure with conventional clips. Treatment
options were discussed and informed consent was given for an attempt at
endoscopic closure using a novel radial closure device ('Padlock clip') combined
with surgical de-epithelialisation, with the understanding that this device has
never previously been used in this setting. At follow-up 2 weeks postprocedure,
the patient was asymptomatic with complete healing of the GCF. This approach has
advantages over other endoscopic closure techniques and can be considered as an
alternative approach to GCF closure.
PMID- 26420696
TI - ST segment elevation myocardial infarction of a rare aetiology: an unexpected
diagnosis.
AB - A 43-year-old man presenting with acute coronary syndrome with ST segment
elevation myocardial infarction underwent urgent coronary angiography. During the
intervention, the patient was found to have several multiple filling defects with
dynamic obstruction in the left coronary circulation. Thrombectomy was performed
on distal left anterior descending artery and 2nd diagonal artery lesions with
balloon angioplasty, which was unsuccessful. Considering the dynamic obstruction
in the angiogram, immediate imaging was performed for structural evaluation of
the heart. Cardiac CT revealed a circumferential groove on the heart, suggesting
an external compression leading to dynamic obstruction of the coronary arteries
on angiogram. Cardiac hernia, a very rare aetiology, was suspected to be the
culprit for the ST segment elevation myocardial infarction. Thoracoscopy was
performed, which revealed congenital cardiac hernia and a fibrous pericardial
band encircling the apex. A left mini thoracotomy was performed to release the
constriction imposed over the heart, with improvement in circulation.
PMID- 26420697
TI - Combined laparoscopic-assisted nephrectomy and complete mesocolic excision for
synchronous renal and colon cancers.
AB - Cancers of the colon and kidney are common malignancies, however, the occurrence
of primary synchronous neoplasms of these two organs is uncommon. To the best of
our knowledge, this is the first case report of a laparoscopic radical left
nephrectomy and extended right complete mesocolic excision (CME) for a patient
with synchronous renal and colon cancers. While a radical nephrectomy has long
been the standard of care for a renal malignancy, CME has only recently been
used. Combined surgeries provide the patient with various benefits such as
decreased hospital stay, less postoperative pain and morbidity, early return to
work and better cosmoses.
PMID- 26420698
TI - Upper gastrointestinal bleed associated with cholinesterase inhibitor use.
AB - An 86-year-old man was admitted with a 3-day history of melaena and syncope. He
was haemodynamically compromised and anaemic on presentation. His only medical
history was mild Alzheimer's disease diagnosed 6 months prior. For this, he was
on donepezil, a cholinesterase inhibitor (ChEI), with a recent dose increase 3
months earlier. After fluid resuscitation with packed red cells, an endoscopy was
performed, which showed an acute duodenal ulcer. This was treated with a high
dose proton pump inhibitor. The patient recovered well and was discharged on
donepezil with the addition of a gastro-protective proton pump inhibitor. In view
of other absent risk factors of upper gastrointestinal haemorrhage, donepezil was
the likely causative agent. ChEIs are associated with frequent side effects and
increased hospitalisation due to central and peripheral increase in
acetylcholine. With this case report, we review the literature of side effects
related to ChEIs, where the mechanisms of action, complications and appropriate
management are discussed.
PMID- 26420699
TI - Osteoblastoma of the coracoid process: an unusual location.
AB - Bone tumours arising from the coracoid process of the scapula are very rare. We
present a case of a 19-year-old man with left shoulder pain for 1 year, with
associated infraclavicular swelling for 8 months. Examination revealed a tender,
bony, hard swelling measuring 3*4 cm. Imaging revealed an expansile osteolytic
lesion arising from the coracoid process with loss of corticomedullary
differentiation. MRI showed altered signal in the adjacent soft tissues. The
patient underwent en bloc resection of the lesion. Histology was suggestive of
osteoblastoma. At the end of 2 years follow-up, the patient had no pain or
recurrence of the lesion. We present this case for its rare location and have
briefly discussed the difficulties in diagnosis of this condition.
PMID- 26420700
TI - Thrombocytopenia and absent radius (TAR) syndrome in pregnancy.
PMID- 26420701
TI - Unusual diagnosis of a solitary thyroid nodule in the paediatric population:
cervical thymic cyst.
AB - We present a case of an 8-year-old girl with a painless swelling in her neck. An
ultrasonogram revealed a cystic nodule with internal echoes, lying posterior to
right lobe of thyroid, and MRI confirmed it. Thyroid scintigraphy did not show
any uptake in the swelling. Intraoperatively, the lesion was densely adherent to
the thyroid gland, hence a hemithyroidectomy was performed. Histopathology showed
it to be an ectopic cervical thymic cyst with parathyroid tissue.
PMID- 26420702
TI - Landau-Kleffner syndrome: an uncommon dealt with case in Southeast Asia.
AB - An 11-year-old boy was admitted with fever followed by convulsions. He had
developed aphasia subsequent to this illness. His birth history was unremarkable,
and he had normal growth and development including of language, hearing and
vision. His neurological examination was normal except for aphasia.
Investigations including cerebrospinal fluid study and MRI were normal. However,
EEG was abnormal and the boy was diagnosed as a case of Landau-Kleffner syndrome
(LKS) and treated with sodium valproate, levetiracetam and steroids. He responded
well to treatment and has been on follow-up for the last 4 months. We present
this case of LKS to increase awareness about early diagnosis and to highlight the
importance of appropriate management for a better outcome.
PMID- 26420703
TI - Amino acids, peptides, and proteins as chemically bonded stationary phases--A
review.
AB - The selectivity of chromatographic separation depends mostly on the stationary
phase and mobile phase composition. Despite being a material with bonded simple
organic molecule, a wide group of stationary phases contain immobilized compound
that possesses biological activity. Stationary phases that contain amino acids
and peptides as well as enzymes and proteins are alternative materials that may
be used for liquid chromatographic separations and are reviewed in this work. In
the case of peptide-bonded stationary phases, most of these types of materials
were elaborated in the 1970s and 1980s; however, over the last few years a
growing interest has been observed which is connected with hydrophilic
interaction liquid chromatography. The most important application of amino acid
and peptide-bonded stationary phases is connected with separation of amino acids,
their derivatives, and peptides. The main advantage of such materials is the
ability for chiral separations.
PMID- 26420704
TI - Isolation of Lipid Rafts from Human Neutrophils by Density Gradient
Centrifugation.
AB - Neutrophils are present within minutes to the site of aggression in the body
making them one of the first cells of the immune system to be in contact with
incoming threats. The cell functions of neutrophils are elicited through the
engagement of surface receptors, some of which are located in a specific region
of the membrane called lipid rafts, a functionally segregated region of the
membrane enriched with cholesterol and distinct species of sphingomyelin and
glycerophospholipids. Lipid rafts are relatively resistant to detergent
extraction and this can be taken advantage of to isolate them from the rest of
the cell membrane. This chapter will describe a reliable method to obtain lipid
rafts from detergent-resistant membrane fractions of human neutrophils. Cells are
lysed in an HEPES solution containing 0.5% Triton X-100, supernatants are mixed
with a 42% sucrose solution, which is then overlaid with a 35% and 5% sucrose
solution. The gradient is centrifuged for 16 h and the resulting fractions can be
further analyzed by immunoblotting or subjected to immunoprecipitation.
PMID- 26420705
TI - Flow Cytometry Analysis of NK Cell Phenotype and Function in Aging.
AB - Natural killer (NK) cells represent a subpopulation of lymphocytes involved in
innate immunity, defined recently as group 1 of innate lymphoid cells (ILCs). NK
cells are cytotoxic lymphocytes with a relevant role in the destruction of
transformed cells as virus-infected or tumor cells, as well as the regulation of
the immune response through cytokine and chemokine production that activates
other cellular components of innate and adaptive immunity. In humans, NK cell
subsets have been defined according to the level of expression of CD56. Aging
differentially affects NK cell subsets and NK cell function. Here, we describe
protocols for the delineation of NK cell subsets and the analysis of their
functional capacity using multiparametric flow cytometry.
PMID- 26420706
TI - Flow Cytometric Identification of Fibrocytes in the Human Circulation.
AB - Because the incidence of organ fibrosis increases with age, various fibrosing
disorders are projected to account for significant increases in morbidity,
mortality, and healthcare costs in the years to come. Treatments for these
diseases are scarce and better understanding of the immunopathogenesis of
fibrosis and its relationship to aging are sorely needed. One area of interest in
this field is the role that fibrocytes might play in the development of tissue
remodeling and fibrosis. Fibrocytes are mesenchymal progenitor cells presumed to
be of monocyte origin that possess the tissue remodeling properties of tissue
resident fibroblasts such as extracellular matrix production and alpha-SMA
related contractile properties, as well as the immunologic functions typically
attributed to macrophages including production of cytokines and chemokines,
antigen presentation, regulation of leukocyte trafficking, and modulation of
angiogenesis. Fibrocytes could participate in the development of age-related
fibrosing disorders through any or all of these functions. This chapter presents
methods that have been developed for the study of circulating human fibrocytes.
Protocols for the quantification of fibrocytes in the human circulation will be
presented along with discussion of the technical challenges that are frequently
encountered in this field. It is hoped that this information will facilitate
further investigation of the relationship between fibrocytes, aging, and
fibrosis, and perhaps uncover new areas of study in these difficult-to-treat and
deadly diseases.
PMID- 26420707
TI - Experimental Approaches to Tissue Injury and Repair in Advanced Age.
AB - Cutaneous wound healing is a complex physiological process. This process can be
altered by multiple physiological and pathological factors. Multiple
pathophysiological disturbances act to impair resolution of cutaneous wound
injury, including obesity, diabetes, peripheral vascular disease, and advanced
age. As our longevity increases without a concomitant increase in healthy living
years, it is plausible to assume that problematic wound closure will continue to
consume a large portion of our health care resources. Furthermore, advanced age
is associated with numerous alterations in the innate and adaptive immune
responses that complicate outcomes following cutaneous injury, trauma, or
infection. Thus, models that examine the impact of advanced age on cutaneous
wound repair will be of great benefit to the development of potential
therapeutics that target age-related aberrancies in tissue repair. Herein, we
detail two animal models of tissue injury, excisional wound injury and burn
injury, that can be used to evaluate wound healing in the context of advanced
age. We also describe modifications of these methods to examine wound infection
following either excisional or burn injury. Lastly, we discuss methods of
subsequent tissue analysis following injury. Models described below can be
further adapted to genetically engineered murine strains to study the effects of
aging and other co-morbidities on wound healing.
PMID- 26420708
TI - Multicolor Digital Flow Cytometry in Human Translational Immunology.
AB - By facilitating the simultaneous analysis of parameters from diverse cell
lineages and biological pathways, multicolor flow cytometry is integral to many
studies in human immunology-particularly those in older individuals-where sample
amounts may be limiting. Studies in human cohorts require particular attention to
fluorochrome panel design and procedures to standardize instrument performance;
reproducible instrument conditions (over time and between centers) are crucial to
accurate comparisons and conclusions in the analysis of heterogeneous groups of
human subjects. Here, we describe procedures for multicolor digital flow
cytometry, our experience in flow cytometry panel design and our approach in
standardizing instrument performance using BD Biosciences hardware and software
(BD Biosciences, San Jose, CA). These techniques allow for the generation of
accurate and precise data in a variety of settings.
PMID- 26420709
TI - Flow Cytometry-Based Methods to Characterize Immune Senescence in Nonhuman
Primates.
AB - Flow cytometry is an invaluable technique that can be used to phenotypically and
functionally characterize immune cell populations ex vivo. This technology has
greatly advanced our ability to gain critical insight into age-related changes in
immune function, commonly known as immune senescence. Rodents have been
traditionally used to investigate the molecular mechanisms of immune senescence
because they offer the distinct advantages of an extensive set of reagents, the
presence of genetically modified strains, and a short lifespan that allows for
longevity studies of short duration. More recently, nonhuman primates (NHPs), and
specifically rhesus macaques, have emerged as a leading translational model to
study various aspects of human aging. In contrast to rodents, they share
significant genetic homology as well as physiological and behavioral
characteristics with humans. Furthermore, rhesus macaques are a long-lived
outbred species, which makes them an ideal translational model. Therefore, NHPs
offer a unique opportunity to carry out mechanistic studies under controlled
laboratory conditions (e.g., photoperiod, temperature, diet, and medications) in
a species that closely mimics human biology. Moreover similar techniques (e.g.,
activity recording and MRI) can be used to measure physiological parameters in
NHPs, making direct comparisons between NHP and human data sets possible. In
addition, the outbred genetics of NHPs enables rigorous validation of research
findings that goes beyond proof of principle. Finally, self-selection bias that
is often unavoidable in human clinical trials can be completely eliminated with
NHP studies. Here we describe flow cytometry-based methods to phenotypically and
functionally characterize innate immune cells as well as T and B lymphocyte
subsets from isolated peripheral blood mononuclear cells (PBMC) in rhesus
macaques.
PMID- 26420710
TI - Multiparameter Phenotyping of Human PBMCs Using Mass Cytometry.
AB - The standard for single-cell analysis of phenotype and function in recent decades
has been fluorescence flow cytometry. Mass cytometry is a newer technology that
uses heavy metal ions, rather than fluorochromes, as labels for probes such as
antibodies. The binding of these ion-labeled probes to cells is quantitated by
mass spectrometry. This greatly increases the number of phenotypic and functional
markers that can be probed simultaneously. Here, we review topics that must be
considered when adapting existing flow cytometry panels to mass cytometry
analysis. We present a protocol and representative panels for surface phenotyping
and intracellular cytokine staining (ICS) assays.
PMID- 26420711
TI - Imaging Immunosenescence.
AB - To demonstrate effects of aging visually requires a robust technique that can
reproducibly detect small differences in efficiency or kinetics between groups.
Investigators of aging will greatly appreciate the benefits of Amnis ImageStream
technology ( www.amnis.com/), which combines quantitative flow cytometry with
simultaneous high-resolution digital imaging. Imagestream is quantitative,
reproducible, feasible with limited samples, and it facilitates in-depth
examination of cellular mechanisms between cohorts of samples.
PMID- 26420712
TI - Activation-Induced Cytidine Deaminase and Switched Memory B Cells as Predictors
of Effective In Vivo Responses to the Influenza Vaccine.
AB - Aging impairs humoral immune responses, leading to increased frequency and
severity of infectious diseases and reduced protective effects of vaccination. We
have identified B-cell biomarkers that are reduced by aging and that can be used
as predictive markers of the response of an individual to vaccination. The
identification of these biomarkers will have an impact on the development of
effective vaccines to protect the elderly from infections and other debilitating
diseases.
PMID- 26420713
TI - Analyzing the Effect of Aging on CD8+ T-Cell Phenotype Using Flow Cytometry.
AB - One of the most noticeable changes in T-cell immunity with aging is the expansion
of memory CD8+ T cells, with a decline in naive phenotype T cells that reflects
both diminished thymopoiesis and the effects of chronic antigenic stimulation
with age. Flow cytometry is a useful tool in evaluating immune cells including
the phenotype characteristics of different T-cell subsets. Here, we show flow
cytometric methods measuring the different subsets of human CD8+ T cells that
change with aging.
PMID- 26420714
TI - Cell-Mediated Immune Response to Influenza Using Ex Vivo Stimulation and Assays
of Cytokine and Granzyme B Responses.
AB - The antibody response to vaccination has been the industry and regulatory
standard for evaluating influenza vaccine efficacy. Although antibodies are an
important defense mechanism providing sterilizing immunity, in older adults, the
cellular immune response is also needed for clinical protection against the
serious complications of influenza. Thus, the demonstration of enhanced antibody
responses as a strategy for advancing new influenza vaccines through the standard
clinical development pipeline may fail to translate to enhanced protection in the
older population. In peripheral blood mononuclear cells (PBMC) challenged with
live influenza virus, an increase in the interferon-gamma:interleukin-10 (IFN
gamma:IL-10) ratio and the level of the cytolytic mediator, granzyme B (GrzB),
correlates with protection against influenza in vaccinated older adults. This
chapter provides detailed methods for measuring these cell-mediated immune
responses, which have been validated according to the International Conference on
Harmonisation (ICH) guidelines. These immune correlates could be combined with
antibody responses to improve the prediction of enhanced protection in vaccine
trials in the older population.
PMID- 26420715
TI - Assays for Monitoring Macroautophagy Activity in T cells.
AB - Autophagy is an essential catabolic process that regulates a diverse array of
functions by targeting cellular components for degradation by lysosomes. Studies
in mammalian cells have shown that the regulation of autophagy is highly complex
and optimization of experimental approaches to analyze this process needs to be
developed for each model studied. This chapter provides an overview of two of the
most commonly used ways to monitor autophagy activity in T cell. It involves
description of common techniques, namely Western blot and cell immunostaining,
giving specific recommendations for working with T cells and monitoring
macroautophagy. We also discuss the analysis required for correct interpretation
of the results and quantification of macroautophagy activity.
PMID- 26420716
TI - Fluorescence-Based Approaches for Quantitative Assessment of Protein
Carbonylation, Protein Disulfides, and Protein Conformation in Biological
Tissues.
AB - Protein oxidation and misfolding have been considered as key players for
progression of aging and etiology of various pathological conditions. However,
few attempts have been made to develop sensitive and reproducible assays to
quantify the changes in protein oxidation and alteration in structure. Here we
describe three distinct fluorescence-based assays to quantify changes in protein
oxidation, namely carbonylation and disulfides and alteration in protein surface
hydrophobicity as a reporter for protein conformation. These techniques will
provide investigators the opportunity to address important biological questions
in their experimental models.
PMID- 26420717
TI - Monitoring the DNA Damage Response at Dysfunctional Telomeres.
AB - Telomeres are repetitive DNA repeats that cap the ends of all eukaryotic
chromosomes. Their proper maintenance is essential for genomic stability and
cellular viability. Dysfunctional telomeres could arise through natural attrition
of telomeric DNA or due to the removal of shelterin components. These uncapped
chromosomal ends are recognized as DSBs by the DDR pathway, leading to the
accumulation of DNA damage sensors at telomeres. The association of these DDR
proteins with dysfunctional telomeres forms telomere dysfunction induced DNA
damage foci (TIFs). Detection of TIFs at telomeres provides an opportunity to
quantify the extent of telomere dysfunction and monitor downstream DNA damage
signaling pathways. Here we describe a method for the detection of TIFs using a
fluorescent in situ hybridization (FISH) approach.
PMID- 26420718
TI - Single-Cell Analysis of T-Cell Receptor alphabeta Repertoire.
AB - The unbiased, paired analysis of T-cell receptor (TCR) alpha- and beta-chain
usage at the single-cell level provides a valuable window of understanding into
the TCR repertoire and the nature of the immune response. Earlier technologies
for TCR repertoire analysis were often limited to examining TCR complementarity
determining region 3 (CDR3) beta expression or required in vitro cloning
procedures that can artificially skew the TCR repertoire from its in vivo state.
We describe here a direct ex vivo, single-cell-based strategy for the clonotypic
analysis of TCRalphabeta repertoires that utilizes multiplexed panels of TCRalpha
and TCRbeta-specific primers in a nested PCR to amplify expressed transcripts
from individual, epitope-specific T cells. This strategy yields the paired
TCRalphabeta sequences of any given population of alphabeta T cells of interest.
PMID- 26420719
TI - Assessment of B Cell Repertoire in Humans.
AB - The B cell receptor (BCR) repertoire is highly diverse. Repertoire diversity is
achieved centrally by somatic recombination of immunoglobulin (Ig) genes and
peripherally by somatic hypermutation and Ig heavy chain class-switching.
Throughout these processes, there is selection for functional gene
rearrangements, selection against gene combinations resulting in self-reactive
BCRs, and selection for BCRs with high affinity for exogenous antigens after
challenge. Hence, investigation of BCR repertoires from different groups of B
cells can provide information on stages of B cell development and shed light on
the etiology of B cell pathologies. In most instances, the third complementarity
determining region of the Ig heavy chain (CDR-H3) contributes the majority of
amino acids to the antibody/antigen binding interface. Although CDR-H3
spectratype analysis provides information on the overall diversity of BCR
repertoires, this fairly simple technique analyzes the relative quantities of CDR
H3 regions of each size, within a range of approximately 10-80 bp, without
sequence detail and thus is limited in scope. High-throughput sequencing (HTS)
techniques on the Roche 454 GS FLX Titanium system, however, can generate a wide
coverage of Ig sequences to provide more qualitative data such as V, D, and J
usage as well as detailed CDR3 sequence information. Here we present protocols in
detail for CDR-H3 spectratype analysis and HTS of human BCR repertoires.
PMID- 26420720
TI - Laboratory and Data Analysis Methods for Characterization of Human B Cell
Repertoires by High-Throughput DNA Sequencing.
AB - High-throughput DNA sequencing techniques have greatly accelerated the pace of
research into the repertoires of antibody and T cell receptor gene rearrangements
that confer antigen specificity to adaptive immune responses. Studies of aging
related changes in human B cell repertoires have benefited from the ability to
detect and quantify thousands to millions of B cell clones in human samples, and
study the mutational lineages and isotype switching relationships within each
clonal lineage. Correlation of repertoire analysis with antibody gene data from
antigen-specific B cells is poised to give much greater insight into clinically
relevant B cell responses and memory storage. Here, we describe strategies for
preparing and analyzing human antibody gene libraries for studying B cell
repertoires.
PMID- 26420721
TI - Discovery of Novel microRNAs in Aging Caenorhabditis elegans.
AB - The rapid development of deep sequencing technologies over the last few years and
concomitant increases in sequencing depth and cost efficiencies have opened the
door to a ever-widening range of applications in biology-from whole-genome
sequencing, to ChIP-seq analysis, epigenomic and RNA transcriptome surveys. Here
we describe the application of deep sequencing to the discovery of novel
microRNAs and characterization of their differential expression during adulthood
in Caenorhabditis elegans.
PMID- 26420722
TI - Analysis of DNA Methylation by Pyrosequencing.
AB - Pyrosequencing is a technique that uses a sequencing-by-synthesis system which is
designed to quantify single-nucleotide polymorphisms (SNPs). Artificial C/T SNP
creation via bisulfite modification permits measurement of DNA methylation
locally and globally in real time. Alteration in DNA methylation has been
implicated in aging, as well as aging-related conditions such as cancer, as well
as cardiovascular, neurodegenerative, and autoimmune diseases. Considering its
ubiquitous presence in divergent clinical pathologies, quantitative analysis of
DNA CpG methylation both globally and at individual genes helps to elucidate the
regulation of genes involved in pathophysiological conditions. The ability to
detect and quantify the methylation pattern of DNA has the potential to serve as
an early detection marker and potential drug target for several diseases. Here,
we provide a detailed technical protocol for pyrosequencing supplemented by
critical information about assay design and nuances of the system that provides a
strong foundation for beginners in the field.
PMID- 26420724
TI - Synthetic Curcumin Analogs as Inhibitors of beta -Amyloid Peptide Aggregation:
Potential Therapeutic and Diagnostic Agents for Alzheimer's Disease.
AB - There is a crucial need to develop new effective drugs for Alzheimer's disease
(AD) as the currently available AD treatments provide only momentary and
incomplete symptomatic relief. Amongst natural products, curcumin, a major
constituent of turmeric, has been intensively investigated for its
neuroprotective effect against beta-amyloid (Abeta)-induced toxicity in cultured
neuronal cells. The ability of curcumin to attach to Abeta peptide and prevent
its accumulation is attributed to its three structural characteristics such as
the presence of two aromatic end groups and their co-planarity, the length and
rigidity of the linker region and the substitution conformation of these
aromatics. However, curcumin failed to reach adequate brain levels after oral
absorption in AD clinical trials due to its low water solubility and poor oral
bioavailability. A number of new curcumin analogs that mimic the active site of
the compound along with analogs that mimic the curcumin anti-amyloid effect
combined with anticholinesterase effect have been developed to enhance the
bioavailability, pharmacokinetics, water solubility, stability at physiological
conditions and delivery of curcumin. In this article, we have summarized all
reported synthetic analogs of curcumin showing effects on beta-amyloid and
discussed their potential as therapeutic and diagnostic agents for AD.
PMID- 26420725
TI - Systematic review and network meta-analysis comparing clinical outcomes and
effectiveness of surgical treatments for haemorrhoids.
AB - BACKGROUND: The aim was to compare the clinical outcomes and effectiveness of
surgical treatments for haemorrhoids. METHODS: Randomized clinical trials were
identified by means of a systematic review. A Bayesian network meta-analysis was
performed using the Markov chain Monte Carlo method in WinBUGS. RESULTS: Ninety
eight trials were included with 7827 participants and 11 surgical treatments for
grade III and IV haemorrhoids. Open, closed and radiofrequency
haemorrhoidectomies resulted in significantly more postoperative complications
than transanal haemorrhoidal dearterialization (THD), LigaSureTM and Harmonic(r)
haemorrhoidectomies. THD had significantly less postoperative bleeding than open
and stapled procedures, and resulted in significantly fewer emergency
reoperations than open, closed, stapled and LigaSureTM haemorrhoidectomies. Open
and closed haemorrhoidectomies resulted in more pain on postoperative day 1 than
stapled, THD, LigaSureTM and Harmonic(r) procedures. After stapled, LigaSureTM
and Harmonic(r) haemorrhoidectomies patients resumed normal daily activities
earlier than after open and closed procedures. THD provided the earliest time to
first bowel movement. The stapled and THD groups had significantly higher
haemorrhoid recurrence rates than the open, closed and LigaSureTM groups.
Recurrence of haemorrhoidal symptoms was more common after stapled
haemorrhoidectomy than after open and LigaSureTM operations. No significant
difference was identified between treatments for anal stenosis, incontinence and
perianal skin tags. CONCLUSION: Open and closed haemorrhoidectomies resulted in
more postoperative complications and slower recovery, but fewer haemorrhoid
recurrences. THD and stapled haemorrhoidectomies were associated with decreased
postoperative pain and faster recovery, but higher recurrence rates. The
advantages and disadvantages of each surgical treatment should be discussed with
the patient before surgery to allow an informed decision to be made.
PMID- 26420726
TI - Adenosquamous carcinoma of the ampulla of Vater: a case report and literature
review.
AB - BACKGROUND: Adenosquamous carcinoma of the ampulla of Vater is extremely rare,
and its clinicopathological features are limited and described in few previous
case reports. Here, we report curative resection of adenosquamous carcinoma of
the ampulla of Vater at an early stage. CASE PRESENTATION: An 81-year-old woman
was referred to our hospital for investigation of the frequent elevation of
hepatic and biliary enzymes and dilatation of the intrahepatic bile ducts.
Preoperative examinations revealed an exposed reddish tumor in the ampulla of
Vater, which was diagnosed on biopsy to be adenocarcinoma with squamous cell
carcinoma component. Pylorus-preserving pancreaticoduodenectomy with regional
lymph node dissection was performed. Pathological examinations revealed the
presence of two malignant components in the lesion, including poorly
differentiated tubular adenocarcinoma and squamous cell carcinoma, without
invasion beyond the sphincter of Oddi or into the duodenal submucosa. These
squamous cell carcinoma and adenocarcinoma components in the tumor comprised
approximately 30 and 70% of the lesion, respectively. No metastasis into regional
lymph nodes was observed, and the patient experienced no tumor recurrence or
metastasis until 20 months after surgery. CONCLUSION: We identified only six
reported cases of adenosquamous carcinoma of the ampulla of Vater in the English
literature, and all of these patients died of recurrence within 14 months after
surgery. To the best of our knowledge, this is the first report of adenosquamous
carcinoma of the ampulla of Vater that was curatively resected at an early stage.
Although more number of studies on clinicopathological findings are required to
determine the appropriate surgical indication, we suggest that surgery remains
the mainstay therapy for adenosquamous carcinoma of the ampulla of Vater detected
at an early stage.
PMID- 26420723
TI - Recent Advances in Discovering the Role of CCL5 in Metastatic Breast Cancer.
AB - A variety of therapeutic strategies are currently under investigation to inhibit
factors that promote tumor invasion, as metastasis is the most common cause of
mortality for cancer patients. Notably, considerable emphasis has been placed on
studying metastasis as a dynamic process that is highly dependent on the tumor
microenvironment. In regards to breast cancer, chemokine C-C motif ligand 5
(CCL5), which is produced by tumor-associated stromal cells, has been established
as an important contributor to metastatic disease. This review summarizes recent
discoveries uncovering the role of this chemokine in breast cancer metastasis,
including conditions that increase the generation of CCL5 and effects induced by
this signaling pathway. In particular, CCL-5-mediated cancer cell migration and
invasion are discussed in the context of intertwined feedback loops between
breast cancer cells and stromal cells. Moreover, the potential use of CCL5 and
its receptor chemokine C-C motif receptor 5 (CCR5) as targets for preventing
breast cancer metastasis is also reviewed.
PMID- 26420727
TI - Motor function benefits of visual restoration measured in age-related cataract
and simulated patients: Case-control and clinical experimental studies.
AB - The aim of the present study was to measure gait velocity in cataract and
simulated patients. The study was performed on 239 cataract patients, 115 age
matched subjects, and 11 simulated patients. We measured gait velocity and
analyzed gait using a three-dimensional motion analysis system. Mean gait
velocity before and 2 and 7 months after cataract surgery was 0.91 +/- 0.19, 1.04
+/- 0.21, and 1.06 +/- 0.21 m/s, respectively, for males and 0.84 +/- 0.22, 0.91
+/- 0.24, and 0.92 +/- 0.25 m/s, respectively, for females. The increase after
surgery was significant in both groups at 7 months (P < 0.05). Gait velocity was
significantly slower in cataract patients compared with controls before surgery,
but no longer different after surgery. In simulated patients, mean velocity was
87.0 +/- 11.4% of normal vision with a 3 degrees visual field and 92.4 +/- 12.3%
of normal when counting fingers. Initial velocity was 89.1 +/- 14.6% of normal
vision with a 3 degrees visual field and 92.7 +/- 11.6% of normal when counting
fingers. There was a significant difference between normal and impaired visual
function (P < 0.05). The results demonstrate the close relationship between
visual function and gait in cataract patients and simulated patients.
PMID- 26420729
TI - Cobalt(III)-Catalyzed C-H/N-O Functionalizations: Isohypsic Access to
Isoquinolines.
AB - C-H/N-O functionalizations by cobalt(III) catalysis allowed the expedient
synthesis of a broad range of isoquinolines. Thus, internal and challenging
terminal alkynes proved to be viable substrates for an isohypsic annulation,
which was shown to proceed by a facile C-H cobaltation.
PMID- 26420728
TI - Impact of ABO blood group on the prognosis of patients undergoing surgery for
esophageal cancer.
AB - BACKGROUND: ABO blood type is an established prognostic factor in several
malignancies, but its role in esophageal cancer (EC) is largely unknown. The aim
of this study is to determine whether ABO blood group is associated with survival
after esophagectomy for EC. METHODS: A total of 406 patients who underwent
surgery for EC were enrolled. The associations of ABO blood group with clinical
and pathological variables were assessed using chi-square test. Associations of
ABO blood group with the survival were estimated using univariable and
multivariable Cox proportional hazards regression models. RESULTS: The ABO blood
group proportionally associated with the grade of EC tumor (P = 0.049). The ABO
blood group status did not correlate with disease-free survival (DFS) in
univariable analysis or multivariable analysis (P > 0.05). And there was no
significant relationship between the ABO blood group and overall survival (OS) in
univariable analysis or multivariable analysis (P > 0.05). CONCLUSIONS: Our
results suggested that no association between ABO blood group and the survival
was observed in patients undergoing surgery for EC.
PMID- 26420730
TI - An integrated system for optical and electrical detection of single
molecules/particles inside a solid-state nanopore.
AB - Nanopore techniques have proven to be useful tools for single-molecule detection.
The combination of optical detection and ionic current measurements enables a new
possibility for the parallel readout of multiple nanopores without complex
nanofluidics and embedded electrodes. In this study, we developed a new
integrated system for the label-free optical and electrical detection of single
molecules based on a metal-coated nanopore. The entire system, containing a dark
field microscopy system and an ultralow current detection system with high
temporal resolution, was designed and fabricated. An Au-coated nanopore was used
to generate the optical signal. Light scattering from a single Au-coated nanopore
was measured under a dark-field microscope. A lab-built ultralow current
detection system was designed for the correlated optical and electrical readout.
This integrated system might provide more direct and detailed information on
single analytes inside the nanopore compared with classical ionic current
measurements.
PMID- 26420731
TI - Shortfalls in basic paediatric asthma education in healthcare professionals.
PMID- 26420732
TI - Effectiveness of a 5-year school-based intervention programme to reduce adiposity
and improve fitness and lifestyle in Indian children; the SYM-KEM study.
AB - DESIGN: Non-randomised non-blinded school-based intervention study. SETTING: Two
schools in the cities of Pune and Nasik, India. PARTICIPANTS: The intervention
group comprised children attending a Pune school from 7-10 years until 12-15
years of age. Two control groups comprised children of the same age attending a
similar school in Nasik, and children in the Pune intervention school but aged 12
15 years at the start of the study. INTERVENTION: A 5-year multi-intervention
programme, covering three domains: physical activity, diet and general health,
and including increased extracurricular and intracurricular physical activity
sessions; daily yoga-based breathing exercises; making physical activity a
'scoring' subject; nutrition education; healthier school meals; removal of fast
food hawkers from the school environs; and health and nutrition education for
teachers, pupils and families. MAIN OUTCOME MEASURES: Body mass index (BMI),
waist circumference, physical fitness according to simple tests of strength,
flexibility and endurance; diet; and lifestyle indicators (time watching TV,
studying and actively playing). RESULTS: After 5 years the intervention children
were fitter than controls in running, long jump, sit-up and push-up tests (p<0.05
for all). They reported spending less time sedentary (watching TV and studying),
more time actively playing and eating fruit more often (p<0.05). The intervention
did not reduce BMI or the prevalence of overweight/obesity, but waist
circumference was lower than in the Pune controls (p=0.004). CONCLUSIONS: It was
possible to achieve multiple health-promoting changes in an academically
competitive Indian school. These changes resulted in improved physical fitness,
but had no impact on the children's BMI or on the prevalence of
overweight/obesity.
PMID- 26420733
TI - Indocyanine green (ICG) fluorescence-guided laparoscopic adrenalectomy.
AB - OBJECTIVE: Laparoscopic adrenalectomy has become the standard of care for many
adrenal tumors. However, the success of the operation hinges on identifying the
adrenal vein and complete tumor resection. We demonstrate the use of a
commercially available near infrared fluorescent imaging system to clearly
delineate the vascular anatomy of adrenal neoplasms and enhance the border
between tumor and normal tissue. We hypothesize that this will increase the
safety of laparoscopic adrenalectomy. MATERIALS AND METHODS: We performed
laparoscopic adrenalectomy utilizing indocyanine green (ICG) and a specialized
laparoscopic fluorescence imaging system on four consecutive patients undergoing
laparoscopic adrenalectomy over a 4-month period. RESULTS: The adrenal arteries
and vein were vividly enhanced with ICG fluorescence guidance, and the border
between tumor and adjacent tissue was clearly demarcated. The operations were
performed safely with minimal blood loss and short operative times. There were no
complications. CONCLUSIONS: Adrenal neoplasms can be resected laparoscopically
under ICG fluorescence guidance and can be used to clearly identify vascular
structures and enhance the borders of the tumor. This technique allows for clear
identification of the adrenal vein and has the potential to improve the safety of
laparoscopic adrenalectomy.
PMID- 26420734
TI - Pathogenenic variant in the COL2A1 gene is associated with Spondyloepiphyseal
dysplasia type Stanescu.
PMID- 26420735
TI - Calcium supplements do not prevent fractures.
PMID- 26420737
TI - Alphabet Soup.
PMID- 26420736
TI - Diagnostic Accuracy of 2-Dimensional Computed Tomography for Articular
Involvement and Fracture Pattern of Posterior Malleolar Fractures.
AB - BACKGROUND: Up to 44% of ankle fractures have involvement of the posterior tibial
margin. Fracture size and morphology are important factors to guide treatment of
these fragments, but reliability of plain radiography in estimating size is low.
The aim of the current study was to evaluate the accuracy of 2-dimensional
computed tomography (2DCT) in the assessment of posterior malleolar fractures.
Additionally, the diagnostic accuracy of 2DCT and its value in preoperative
planning was evaluated. METHODS: Thirty-one patients with 31 ankle fractures
including a posterior malleolar fragment were selected. Preoperative CT scans
were analyzed by 50 observers from 23 countries. Quantitative 3-dimensional CT
(Q3DCT) reconstructions were used as a reference standard. RESULTS: Articular
involvement of the posterior fragment was overestimated on 2DCT by factors 1.6,
1.4, and 2.2 for Haraguchi types I, II, and III, respectively. Interobserver
agreement on operative management ("to fix, or not to fix?") was substantial
(kappa = 0.69) for Haraguchi type I fractures, fair (kappa = 0.23) for type II
fractures, and poor (kappa = 0.09) for type III fractures. 2DCT images led to a
change in treatment of the posterior malleolus in 23% of all fractures. Surgeons
would operatively treat type I fractures in 63%, type II fractures in 67%, and
type III fractures in 22%. CONCLUSION: Surgeons overestimated true articular
involvement of posterior malleolar fractures on 2DCT scans. 2DCT showed some
additional value in estimating the involved articular surface when compared to
plain radiographs; however, this seemed not yet sufficient to accurately read the
fractures. Analysis of the CT images showed a significant influence on choice of
treatment in 23% with a shift toward operative treatment in 12% of cases compared
to evaluating plain lateral radiographs alone. LEVEL OF EVIDENCE: Level III,
comparative study.
PMID- 26420738
TI - The effects of iodine blocking following nuclear accidents on thyroid cancer,
hypothyroidism, and benign thyroid nodules: design of a systematic review.
AB - BACKGROUND: One of the most efficient radiation protection methods to reduce the
risk of adverse health outcomes in case of accidental radioactive iodine release
is the administration of potassium iodine (KI). Although KI administration is
recommended by WHO's guidelines for iodine prophylaxis following nuclear
accidents and is also widely implemented in most national guidelines, the
scientific evidence for the guidelines lacks as the guidelines are mostly based
on expert opinions and recommendations. Therefore, this study will provide
evidence by systematically reviewing the effects of KI administration in case of
accidental radioactive iodine release on thyroid cancer, hypothyroidism, and
benign nodules. METHODS: We will apply standard systematic review methodology for
the identification of eligible studies, data extraction, assessment of risk of
biases, heterogeneity, and data synthesis. The electronic database search will be
conducted in MEDLINE (via PubMed) and EMBASE, and covers three search blocks with
terms related to the health condition, intervention, and occurrence/location. We
have no date or language restrictions, but restrictions to humans only. We will
include studies comparing the effects of KI administration on thyroid cancer,
hypothyroidism, and benign thyroid nodules in a population exposed to radioactive
iodine release. The quality of the studies will be graded. If feasible, a meta
analysis will be conducted. DISCUSSION: This proposed systematic review will
update the existing WHO guideline from 1999. New evidence on the efficacy of KI
administration to reduce thyroid cancer, hypothyroidism, and benign thyroid
nodules in the event of an accidental release of radioactive iodine to the
environment will provide the basis for an update of the WHO guideline for iodine
prophylaxis following nuclear accidents. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
CRD42015024340.
PMID- 26420739
TI - Computational models of visual attention.
PMID- 26420740
TI - Drainage of the Left Hepatic Vein into the Coronary Sinus, a Rare Intraoperative
Finding.
AB - In a 76-year-old female undergoing coronary artery bypass surgery, a persistent
left hepatic vein was observed. Draining of this vein into the coronary sinus is
an extremely rare embryological malformation and this is the first case to be
reported as a solitary malformation in absence of other cardiac malformations.
PMID- 26420742
TI - Construction and validation of a scale of assessment of self-care behaviours
anticipatory to creation of arteriovenous fistula.
AB - AIMS AND OBJECTIVES: We developed a scale to assess the self-care behaviours
developed by patients with end-stage renal disease to preserve the vascular
network prior to construction of arteriovenous fistula. BACKGROUND: The
possibility of creation of an arteriovenous fistula depends on the existence of
an arterial and venous network in good condition, namely the size and elasticity
of the vessels. It is essential to teach the person to develop self-care
behaviours for the preservation of the vascular network, regardless of the
modality of dialysis selected. DESIGN: Methodological study. METHODS: The scale
was developed based on clinical experience and research conducted by the
researcher in the area of the vascular access for haemodialysis. The content of
the scale was judged by two panels of experts for content validity. The revised
version of the scale was administered to a convenience sample of 90 patients with
end-stage renal disease. In the statistical analysis, we used the Cronbach's
alpha, the Kaiser-Meyer-Olkin and scree plot and the principal component analysis
with varimax rotation. RESULTS: A principal component analysis confirmed the
univariate structure of the scale (KMO = 0.759, Bartlett's sphericity test
approximate chi(2) 142.201, p < 0.000). Cronbach's alpha is 0.831, varying
between 0.711-0.879. CONCLUSION: This scale revealed properties that allow its
use to assess the patients self-care behaviours regarding the preservation of the
vascular network. RELEVANCE TO CLINICAL PRACTICE: This scale can be used to
evaluate educational programmes for the development of self-care behaviours in
the preservation of vascular network. This scale can identify not only the
patients that are able to take care of their vascular network but also the
proportion of patients who are not able to do it, that need to be educated.
PMID- 26420743
TI - Associations between allelic polymorphism of the BMP Binding Endothelial
Regulator and phenotypic variation of cattle.
AB - The BMP Binding Endothelial Regulator (BMPER) is an inhibitor of bone
morphogenetic proteins (BMPs), which play fundamental roles in adipocyte
differentiation, fat development and energy balance. The objectives of this study
were to detect polymorphisms of BMPER gene in four indigenous Chinese cattle
populations and to investigate their effects on body size traits. Initially,
three SNPs, namely G100597A (SNP1), C105331A (SNP2), and G105521A (SNP3) and
eight distinct haplotypes were identified. In a total of 12 SNP-SNP combinations,
SNP2-SNP3 had a strong linkage in Qinchuan cattle. These four cattle populations
belong to intermediate genetic diversity at three SNP loci except Shuxuan cattle
population in SNP3. At SNP1, genotype AA was associated with an increased body
size. For SNP2, the heterozygous genotype individuals had a greater rump length
than those of two other homozygotic genotypes. At SNP3, individuals with GG
genotype had smaller rump length and hip width. A total of seven haplotype
combinations were detected in Qinchuan cattle population and association analysis
results showed individuals with Haplotype combination 4/2 (AAA/CAA) had greater
rump length than those with Hap3/1 and Hap3/3 (P < 0.05). These results strongly
suggest that bovine BMPER gene may be used as a genetic marker for cattle
breeding.
PMID- 26420744
TI - Mechanochromic Fibers with Structural Color.
AB - Responsive photonic crystals have been widely developed to realize tunable
structural colors by manipulating the flow of light. Among them, mechanochromic
photonic crystals attract increasing attention due to the easy operation, high
safety and broad applications. Recently, mechanochromic photonic crystal fibers
were proposed to satisfy the booming wearable smart textile market. In this
Concept, the fundamental mechanism, fabrication, and recent progress on
mechanochromic photonic crystals, especially in fiber shape, are summarized to
represent a new direction in sensing and displaying.
PMID- 26420745
TI - Engaging cultural resources to promote mental health in Dutch LSES neighborhoods:
study of a community-based participatory media project.
AB - Community-based participatory media projects form a promising new strategy for
mental health promotion that can help address the mental health-gap identified by
the World Health Organization. (2008b) mhGAP, Mental Health Gap Action Programme:
Scaling Up Care for Mental, Neurological and Substance Use Disorders. World
Health Organization, Geneva. In this article we present an ethnographic study
about a participatory media project that was developed to promote mental health
in selected Dutch low socio-economic status neighborhoods. Through narrowcastings
(group film viewings), participant observation and interviews we mapped the ways
in which the media project effected and facilitated the collective sense-making
process of the audience with regard to sources of stress impacting mental health
and opportunities for action. These determinants of mental health are shaped by
cultural dimensions, since the cultural context shapes everyday experiences of
stress as well as the resources and skills to manage them. Our analysis shows
that the media project engaged cultural resources to challenge stressful social
scripts. We conclude that more attention should be paid to cultural narratives in
a community to understand how health promotion strategies can support social
resilience.
PMID- 26420746
TI - Annual report of the Committee on Gynecologic Oncology, the Japan Society of
Obstetrics and Gynecology.
AB - The Japan Society of Obstetrics and Gynecology collects and analyzes annual data
on gynecologic cancers from member institutions. Here we present the Treatment
Annual Report for 2007. Data on the prognosis of 3381 patients with cervical
cancer, 3681 with endometrial cancer, and 2367 with ovarian cancer for whom
treatment was initiated in 2007 were analyzed in the Treatment Annual Report. In
the 2007 Treatment Annual Report, stage I accounted for 53.1%, stage II for
24.4%, stage III for 14.2%, and stage IV for 8.3% of all patients with cervical
cancer. Stage I accounted for 64.8%, stage II for 8.2%, stage III for 20.2%, and
stage IV for 6.9% of all patients with endometrial cancer. Stage I accounted for
41.4%, stage II for 9.9%, stage III for 30.6%, and stage IV for 8.6% of all
patients with ovarian cancer. The 5-year overall survival rates for patients with
cervical cancer were 91.8% for stage I, 71.5% for stage II, 53.0% for stage III,
and 23.7% for stage IV; those for patients with endometrial cancer were 95.3%,
89.8%, 75.6%, and 29.1%, and those for patients with ovarian surface epithelial
stromal tumors were 91.5%, 76.1%, 46.9%, and 31.3%, respectively.
PMID- 26420747
TI - In situ associations between marine photosynthetic picoeukaryotes and potential
parasites - a role for fungi?
AB - Photosynthetic picoeukaryotes (PPEs) are important components of the marine
picophytoplankton community playing a critical role in CO2 fixation but also as
bacterivores, particularly in the oligotrophic gyres. Despite an increased
interest in these organisms and an improved understanding of the genetic
diversity of this group, we still know little of the environmental factors
controlling the abundance of these organisms. Here, we investigated the
quantitative importance of eukaryotic parasites in the free-living fraction as
well as in associations with PPEs along a transect in the South Atlantic. Using
tyramide signal amplification-fluorescence in situ hybridization (TSA-FISH), we
provide quantitative evidence of the occurrence of free-living fungi in open
ocean marine systems, while the Perkinsozoa and Syndiniales parasites were not
abundant in these waters. Using flow cytometric cell sorting of different PPE
populations followed by a dual-labelled TSA-FISH approach, we also demonstrate
fungal associations, potentially parasitic, occurring with both pico
Prymnesiophyceae and pico-Chrysophyceae. These data highlight the necessity for
further work investigating the specific role of marine fungi as parasites of
phytoplankton to improve understanding of carbon flow in marine ecosystems.
PMID- 26420748
TI - Electrocatalytic Dihydrogen Production with a Robust Mesoionic Pyridylcarbene
Cobalt Catalyst.
AB - A Co(III) complex with a mesoionic pyridylcarbene ligand is presented. This
complex is an efficient electrocatalyst for H2 production at very low
overpotential and high turnovers when using a (glassy carbon) GC electrode. The
corresponding triazole complexes display no catalytic activity whatsoever under
identical conditions. The remarkable robustness of the Co-C(carbene) bond towards
acids is likely responsible for the high efficiency of this catalyst. The present
results thus open new avenues for carbene-based ligands for generating functional
models for hydrogenases.
PMID- 26420749
TI - Leaving school: a comparison of the worries held by adolescents with and without
intellectual disabilities.
AB - BACKGROUND: Leaving school is an important time for adolescents, with increasing
autonomy and developing adult identities. The present study sought to shed light
on the content and emotional impact of worries amongst adolescents with and
without intellectual disabilities (IDs) at this time of change. METHODS: Twenty
five adolescents with mild to moderate IDs and 27 adolescents without IDs, aged
15 to 18 years, took part in the study. Participants' worries were elicited using
a structured interview. The levels of rumination and distress related to their
most salient worries were also examined, along with their self-reported levels of
anxiety. RESULTS: Content analysis of the interviews identified differences
between the worries of the two groups of participants, with the adolescents with
IDs expressing more general worries about failure and personal threat. Level of
distress about worries was positively correlated with anxiety in both groups. The
adolescents with IDs were significantly more anxious than their non-disabled
peers. CONCLUSIONS: The differences between the groups' worries may be linked to
differences in life experience and expectations. Consideration should be given to
the specific worries of adolescents at the stage of leaving school. Doing so may
allow solutions for their concerns to be identified, thus easing distress and
leading to a less stressful transition.
PMID- 26420750
TI - In Silico Modeling for the Prediction of Dose and Pathway-Related Adverse Effects
in Humans From In Vitro Repeated-Dose Studies.
AB - Long-term repeated-dose toxicity is mainly assessed in animals despite poor
concordance of animal data with human toxicity. Nowadays advanced human in vitro
systems, eg, metabolically competent HepaRG cells, are used for toxicity
screening. Extrapolation of in vitro toxicity to in vivo effects is possible by
reverse dosimetry using pharmacokinetic modeling. We assessed long-term repeated
dose toxicity of bosentan and valproic acid (VPA) in HepaRG cells under serum
free conditions. Upon 28-day exposure, the EC50 values for bosentan and VPA
decreased by 21- and 33-fold, respectively. Using EC(10) as lowest threshold of
toxicity in vitro, we estimated the oral equivalent doses for both test compounds
using a simplified pharmacokinetic model for the extrapolation of in vitro
toxicity to in vivo effect. The model predicts that bosentan is safe at the
considered dose under the assumed conditions upon 4 weeks exposure. For VPA,
hepatotoxicity is predicted for 4% and 47% of the virtual population at the
maximum recommended daily dose after 3 and 4 weeks of exposure, respectively. We
also investigated the changes in the central carbon metabolism of HepaRG cells
exposed to orally bioavailable concentrations of both drugs. These concentrations
are below the 28-day EC(10) and induce significant changes especially in glucose
metabolism and urea production. These metabolic changes may have a pronounced
impact in susceptible patients such as those with compromised liver function and
urea cycle deficiency leading to idiosyncratic toxicity. We show that the
combination of modeling based on in vitro repeated-dose data and metabolic
changes allows the prediction of human relevant in vivo toxicity with mechanistic
insights.
PMID- 26420752
TI - What positive encounters with healthcare and social insurance staff promotes
ability to return to work of long-term sickness absentees?
AB - AIMS: Previous studies suggest that positive encounters with healthcare and
social insurance staff may be important in promoting return to work among long
term sickness absentees. This study aimed to identify more specifically what
positive encounters are important for promoting ability to return to work.
METHODS: A questionnaire about different types of encounters was sent to 10,042
people in Sweden on sick leave for 6-8 months (58% responded). For each positive
encounter, we estimated the marginal probability difference (PD) of return to
work, adjusting for age, sex, education, sick-leave diagnosis, and the sum score
of all other encounters. Adjusting for the other encounters is important since of
the observed variables these were the strongest confounders. RESULTS: The
positive encounters with both healthcare and social insurance staff significantly
associated with promoting ability to return to work after adjusting for the other
positive encounters were "Believed in my work capacity" PD=16.9 (95% CI: 12.0,
21.9) and 12.0 (6.3, 17.7), respectively; "Supported my suggestions for
solutions": 9.5 (3.1, 15.9) and 11.6 (5.7, 17.4); "Was supportive and
encouraging": 10.1 (3.6, 16.7) and 7.3 (1.7, 12.8). Additionally, the encounter
with healthcare staff most strongly associated with promoting return to work was
"Let me take responsibility" 14.8 (7.2, 22.3); and with social security staff:
"Showed that she/he liked me" 10.4 (5.4, 15.4). CONCLUSIONS: Healthcare and
social security staff being supportive, encouraging, and believing in the
sickness absentee's work capacity may be very important for increasing the
probability for long-term sickness absentees' ability to return to work.
PMID- 26420753
TI - Cochlear involvement in patients with ulcerative colitis.
AB - OBJECTIVE: To investigate whether cochlear involvement is an extraintestinal
manifestation in patients with ulcerative colitis. METHOD: Forty-four ulcerative
colitis patients and 44 age-matched healthy subjects were included in the study.
Pure tone and speech audiometry, and distortion product otoacoustic emission
tests were performed on all participants. The audiometric test results were
compared between groups and their relationship with disease activity was
investigated. RESULTS: Pure tone threshold averages were significantly higher in
ulcerative colitis patients compared to controls (p 0.05). CONCLUSION: Even
though hearing thresholds may be within normal limits, decreased distortion
product otoacoustic emission amplitude values indicate a cochlear involvement in
ulcerative colitis patients.
PMID- 26420754
TI - The Temporal Dynamics of Spoken Word Recognition in Adverse Listening Conditions.
AB - This study examined the temporal dynamics of spoken word recognition in noise and
background speech. In two visual-world experiments, English participants listened
to target words while looking at four pictures on the screen: a target (e.g.
candle), an onset competitor (e.g. candy), a rhyme competitor (e.g. sandal), and
an unrelated distractor (e.g. lemon). Target words were presented in quiet, mixed
with broadband noise, or mixed with background speech. Results showed that
lexical competition changes throughout the observation window as a function of
what is presented in the background. These findings suggest that, rather than
being strictly sequential, stream segregation and lexical competition interact
during spoken word recognition.
PMID- 26420751
TI - Revealing Behavioral Learning Deficit Phenotypes Subsequent to In Utero Exposure
to Benzo(a)pyrene.
AB - To characterize behavioral deficits in pre-adolescent offspring exposed in utero
to Benzo(a)pyrene [B(a)P], timed-pregnant Long Evans Hooded rats were treated
with B(a)P (150, 300, 600, and 1200 ug/kg BW) or peanut oil (vehicle) on E14, 15,
16, and 17. Following birth, during the pre-weaning period, B(a)P metabolites
were examined in plasma and whole brain or cerebral cortex from exposed and
control offspring. Tissue concentrations of B(a)P metabolites were (1) dose
dependent and (2) followed a time-dependence for elimination with ~60% reduction
by PND5 in the 1200 ug/kg BW experimental group. Spatial discrimination-reversal
learning was utilized to evaluate potential behavioral neurotoxicity in P40-P60
offspring. Late-adolescent offspring exposed in utero to 600 and 1200 ug/kg BW
were indistinguishable from their control counterparts for ability to acquire an
original discrimination (OD) and reach criterion. However, a dose-dependent
effect of in utero B(a)P-exposure was evident upon a discrimination reversal as
exposed offspring perseverated on the previously correct response. This newly
characterized behavioral deficit phenotype for the first reversal was not
apparent in either the (1) OD or (2) subsequent reversal sessions relative to the
respective control offspring. Furthermore, the expression of activity related
cytoskeletal-associated protein (Arc), an experience-dependent cortical protein
marker known to be up-regulated in response to acquisition of a novel behavior,
was greater in B(a)P-exposed offspring included in the spatial discrimination
cohort versus home cage controls. Collectively, these findings support the
hypothesis that in utero exposure to B(a)P during critical windows of development
representing peak periods of neurogenesis results in behavioral deficits in later
life.
PMID- 26420755
TI - Effect of water-soluble carbohydrate content in orchardgrass pasture on grazing
time and rumen fermentation in dairy cows.
AB - Two experiments were conducted to clarify the effect of water-soluble
carbohydrate (WSC) content in orchardgrass pasture on the diurnal distribution of
grazing time. Six ruminally cannulated, non-lactating dairy cows were grazed on
either of two pastures with different orchardgrass cultivars containing low WSC
(LWSC; cultivar: 'Hokkai 28') or high WSC (HWSC; cultivar: 'Harunemidori'). The
cows were grazed in morning and evening sessions in experiment 1, whereas the
cows were grazed throughout the day in experiment 2. In experiment 1, grazing
time of the cows on HWSC was longer than that of the cows on LWSC (P < 0.01).
This difference was larger in the morning session than in the evening session
(pasture * grazing session: P < 0.05). Effects on herbage intake were similar to
those on grazing time. In experiment 2, daily total grazing time was longer for
the cows on HWSC than for those on LWSC (P < 0.05). The cows on HWSC spent a
longer time grazing than those on LWSC in the morning between 03.00 and 09.00
hours (P < 0.01). The results indicated that prolonged grazing time in the period
between dawn and early morning could increase daily herbage intake in cows grazed
on pastures of orchardgrass cultivars with high-WSC content.
PMID- 26420756
TI - Suppression of the migration and invasion is mediated by triptolide in B16F10
mouse melanoma cells through the NF-kappaB-dependent pathway.
AB - Melanoma cancer is one of the major causes of death in humans worldwide.
Triptolide is one of the active components of Tripterygium wilfordii Hook F, and
has biological activities including induced cell cycle arrest and induction of
apoptosis but its antimetastatic effects on murine melanoma cells have not yet
been elucidated. Herein, we investigated the effect of triptolide on the
inhibition of migration and invasion and possible associated signal pathways in
B16F10 murine melanoma cancer cells. Wound healing assay and Matrigel Cell
Migration Assay and Invasion System demonstrated that triptolide marked
inhibiting the migration and invasion of B16F10 cells. Gelatin zymography assay
demonstrated that triptolide significantly inhibited the activities of matrix
metalloproteinases-2 (MMP-2). Western blotting showed that triptolide markedly
reduced CXCR4, SOS1, GRB2, p-ERK, FAK, p-AKT, Rho A, p-JNK, NF-kappaB, MMP-9, and
MMP-2 but increased PI3K and p-p38 and COX2 after compared to the untreated
(control) cells. Real time PCR indicated that triptolide inhibited the gene
expression of MMP-2, FAK, ROCK-1, and NF-kappaB but did not significantly affect
TIMP-1 and -2 gene expression in B16F10 cells in vitro. EMSA assay also showed
that triptolide inhibited NF-kappaB DNA binding in a dose-dependent manner.
Confocal laser microscopy examination also confirmed that triptolide inhibited
the expression of NF-kappaB in B16F10 cells. Taken together, we suggest that
triptolide inhibited B16F10 cell migration and invasion via the inhibition of NF
kappaB expression then led to suppress MMP-2 and -9 expressions. (c) 2015 Wiley
Periodicals, Inc. Environ Toxicol 31: 1974-1984, 2016.
PMID- 26420757
TI - The effect of chloroform, orange oil and eucalyptol on root canal transportation
in endodontic retreatment.
AB - The purpose of the present study was to assess the effect of solvents on root
canal transportation in endodontic retreatment. Sixty extracted human permanent
mandibular first molars with curved root canals were selected. All of the root
canals were prepared using Twisted File Adaptive instruments (SybronEndo, Orange,
CA, USA) and filled with gutta-percha and AH Plus sealer (Dentsply DeTrey,
Konstanz, Germany) using the cold lateral compaction technique. The teeth were
assigned to four retreatment groups as follows (n = 15): eucalyptol, chloroform,
orange oil and control. The canals were scanned using cone-beam computed
tomography scanning before and after instrumentation. The chloroform group showed
a significantly higher mean transportation value than the orange oil and control
groups at the 3 and 5 mm levels (P = 0.011 and P = 0.003, respectively). There
was no significant difference among the orange oil, eucalyptol and control groups
in terms of canal transportation (P > 0.61). The chloroform led to more canal
transportation than the eucalyptol and orange oil during endodontic retreatment.
PMID- 26420758
TI - Sex differences in parental care: Gametic investment, sexual selection, and
social environment.
AB - Male and female parents often provide different type and amount of care to their
offspring. Three major drivers have been proposed to explain parental sex roles:
(1) differential gametic investment by males and females that precipitates into
sex difference in care, (2) different intensity of sexual selection acting on
males and females, and (3) biased social environment that facilitates the more
common sex to provide more care. Here, we provide the most comprehensive
assessment of these hypotheses using detailed parental care data from 792 bird
species covering 126 families. We found no evidence for the gametic investment
hypothesis: neither gamete sizes nor gamete production by males relative to
females was related to sex difference in parental care. However, sexual selection
correlated with parental sex roles, because the male share in care relative to
female decreased with both extra-pair paternity and frequency of male polygamy.
Parental sex roles were also related to social environment, because male parental
care increased with male-biased adult sex ratios (ASRs). Taken together, our
results are consistent with recent theories suggesting that gametic investment is
not tied to parental sex roles, and highlight the importance of both sexual
selection and ASR in influencing parental sex roles.
PMID- 26420759
TI - Multiwavelength excitation of photosensitizers interacting with gold
nanoparticles and its impact on optical properties of their hybrid mixtures.
AB - In a hybrid mixture of organic (dye) and inorganic (metallic nanoparticles)
components, the optical properties of a dye can be easily controlled by tailoring
the shape or the concentration of the noble metal nanoparticles (NPs). The
influences of multiexcitation (multiwavelength excitation) of photosensitizers
(pheophorbide a and hematoporphyrin) on the interactions with pegylated Au-NPs
and on the photophysical parameters of the dyes are studied. Detailed, systematic
fluorescence quenching studies were performed in the mixtures of different
contents of Au-NPs, and interpreted together with the results of quantum singlet
oxygen yield examinations. According to the results, the fluorescence of the two
dyes studied was effectively quenched in the presence of Au-NPs, mainly because
of the resonance energy transfer between the donor (dye) and the acceptor (Au
NPs). Stern-Volmer quenching constants were determined by a few orders of
magnitude higher than those describing the photochemical quenching process. In
hybrid mixtures analyzed, the mechanism of energy transfer between the donor and
the acceptor was nanometal surface energy transfer. Furthermore, different
behavior of the mixtures on excitation with the wavelengths from the Soret and Q
bands of the dyes and with those corresponding to the surface plasmon resonance
band of Au-NPs was analyzed. Moreover, for certain concentrations of Au-NPs and
for certain excitation wavelengths, an increase in singlet oxygen generation was
observed. The results obtained indicate the significance of further studies of
photosensitizers in hybrid mixtures with NPs.
PMID- 26420760
TI - Spatz 3 Adjustable Intragastric Balloon: Long-Term Safety Concerns.
PMID- 26420761
TI - The Effect of Intraoperative N-Acetylcysteine on Hepatocellular Injury During
Laparoscopic Bariatric Surgery. A Randomised Controlled Trial.
AB - BACKGROUND: The combination of pneumoperitoneum and intraoperative retraction of
the left lobe of the liver leads to hepatocellular injury during laparoscopic
gastric surgery. Fatty livers are more susceptible to ischaemic insults. This
trial investigated whether the antioxidant N-acetylcysteine (NAC) reduced liver
injury during laparoscopic sleeve gastrectomy (LSG). METHODS: Patients undergoing
LSG were randomised (single blinded) to receive intraoperative NAC infusion or
standard anaesthetic treatment. Blood samples were taken before and after surgery
(days 0 to 4). Primary endpoints included serum aminotransferases. Secondary
measures were C-reactive protein, weight cell count (WCC), cytokines (interleukin
6 and 10) and cytokeratin-18 as markers of apoptosis. Intraoperative liver biopsy
samples were assessed using a locally developed injury score. RESULTS: Twenty
patients (14 females, mean age 44.5 (SEM +/- 2.9) years, mean BMI 60.8 (SEM +/-
2.4) kg/m(2)) were recruited (NAC n = 10, control n = 10). The trial was stopped
early after a planned interim analysis. Baseline liver function was similar. The
peak rise in liver enzymes was on day 1, but levels were not significantly
different between the groups. Rates of complications and length of stay were not
significantly different. Secondary outcome measures, including white cell count
(WCC), cytokines and cytokeratin (CK)-18 fragments, were not different between
groups. Liver injury scores did not differ significantly. CONCLUSIONS: NAC did
not reduce intraoperative liver injury in this small number of patients. The
heterogenous nature of the study population, with differences in co-morbidities,
body mass index and intraabdominal anatomy, leads to a varied post-operative
inflammatory response. Significant hepatocyte injury occurs through both necrosis
and apoptosis.
PMID- 26420762
TI - Letter to "Predictive Factors of Type 2 Diabetes Mellitus Remission Following
Bariatric Surgery: a Meta-analysis".
PMID- 26420763
TI - Chronic Non-specific Pain After Gastric Bypass.
PMID- 26420764
TI - Metabolic Surgery Could Restore Hepatic Glucose Metabolism: Results from F-18
Fluorodeoxyglucose Positron Emission Tomography.
PMID- 26420765
TI - Outcomes of Bariatric Surgery in Patients with Inflammatory Bowel Disease.
AB - BACKGROUND: Obesity has become prevalent in patients with inflammatory bowel
disease (IBD). Bariatric surgery can be considered to be contraindicated in IBD
patients. We aimed to evaluate feasibility, safety, and efficacy of bariatric
surgery in IBD patients. METHODS: We retrospectively identified all morbidly
obese patients with a known diagnosis of IBD, who underwent bariatric surgery
between January 2005 and December 2012. Postoperative outcomes and status of IBD
in patients on maintenance therapy for their disease were assessed. RESULTS: We
identified 20 IBD patients including 13 ulcerative colitis (UC) and 7 Crohn's
disease (CD) patients with a mean age of 54.0 +/- 10.5 years, BMI of 50.1 +/- 9.0
kg/m(2), and duration of IBD of 11.3 +/- 5.2 years. Eleven patients were on
medication for IBD at baseline. Bariatric procedures included sleeve gastrectomy
(N = 9), gastric bypass (N = 7), gastric banding (N = 3), and one conversion of
band to gastric bypass. There were no intraoperative complications, but two
conversions to laparotomy due to adhesions. Mean BMI change and excess weight
loss at 1 year was 14.3 +/- 5.7 kg/m(2) and 58.9 +/- 21.1 %, respectively. Seven
early postoperative complications occurred including dehydration (N = 5),
pulmonary embolism (N = 1), and wound infection (N = 1). During a mean follow-up
of 34.6 +/- 21.7 months, five patients developed complications including
pancreatitis (N = 2), ventral hernia (N = 2), and marginal ulcer (N = 1). Nine
out of ten eligible patients experienced improvement in their IBD status.
CONCLUSIONS: Bariatric surgery is feasible and safe in morbidly obese patients
suffering from IBD. In addition to being an effective weight loss procedure,
bariatric surgery may help mitigate symptoms in this patient population.
PMID- 26420766
TI - Pseudorhodoplanes sinuspersici gen. nov., sp. nov., isolated from oil
contaminated soil.
AB - Strain RIPI 110T was isolated from a soil sample collected from an oil
contaminated site on Siri Island, Persian Gulf, Iran. Cells of the novel isolate
were Gram-stain-negative, facultatively anaerobic, non-motile and rod-shaped.
Cells divided asymmetrically by budding and formed rosette-like clusters. The
optimum pH and temperature for growth were pH 7 and 30 degrees C, while the
strain was able to grow at pH 5.5-8 and 15-35 degrees C. Strain RIPI 110T
utilized only complex carbon sources and pyruvate as the sole carbon source and
could not grow under photoautotrophic conditions. The highest 16S rRNA gene
sequence similarities, 93.9, 93.9 and 93.5 %, were obtained with Variibacter
gotjawalensis GJW-30T, Rhodoplanes roseus 941T and Rhodoplanes elegans AS130T,
respectively. The major cellular fatty acids were summed feature 8 (C18 :
1omega7c/omega6c), C16 : 0 and C19 : 0 cyclo omega8c. Polar lipid analyses
revealed that strain RIPI 110T contained phosphatidylethanolamine,
diphosphatidylglycerol, phosphatidylglycerol, an unknown aminophospholipid and
four unknown phospholipids. Ubiquinone-10 was the predominant quinone component.
The DNA G+C content was 59.4 mol%. On the basis of the 16S rRNA gene sequence
analysis, in combination with chemotaxonomic and physiological data, the novel
isolate could not be classified in any recognized genera. Strain RIPI 110T is
thus considered to represent a novel species of a new genus within the order
Rhizobiales, for which the name Pseudorhodoplanes sinuspersici gen. nov., sp.
nov. is proposed. The type strain of the type species is RIPI 110T ( = IBRC-M
10770T = CECT 8374T).
PMID- 26420767
TI - The importance of tissue handling of surgically removed breast cancer for an
accurate assessment of the Ki-67 index.
AB - AIM: Insufficient attention for the Ki-67 immunohistochemistry has been given to
the importance of tissue handling for surgical breast cancer specimens. We sought
to investigate the effect of fixation status on the Ki-67. METHODS: We examined
the effect of fixative, time to and duration of fixation using surgical
specimens, and finally, compared the paired Ki-67 index in the tumour between
core needle and surgical specimen. RESULTS: The Ki-67 was significantly higher
when 10% neutral buffered formalin was used (p=0.0276). Insufficient fixation
caused a drastic reduction in the Ki-67 index (p=0.0177), but not significant in
oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).
Sixteen hours delayed time to fixation also caused a reduction of the Ki-67
(p=0.0284), but not significant in ER. Prolonged fixation significantly led to a
gradual reduction in the Ki-67 in a time-dependent manner, but not in both ER and
HER2. Finally, cutting the tumour before fixation improved fixation status and
consequently caused an increased level of the Ki-67 index (p=0.0181), which
resulted in a strong correlation of the Ki-67 between core needle and surgical
specimen (r=0.8595). CONCLUSIONS: Tissue handling of surgical specimen is
critical for assessing the Ki-67 compared with ER and HER2. We should pay more
attention to tissue fixation status for the standard assessment of the Ki-67
index.
PMID- 26420769
TI - Preference pulses and the win-stay, fix-and-sample model of choice.
AB - Two groups of six rats each were trained to respond to two levers for a food
reinforcer. One group was trained on concurrent variable-ratio 20 extinction
schedules of reinforcement. The second group was trained on a concurrent variable
interval 27-s extinction schedule. In both groups, lever-schedule assignments
changed randomly following reinforcement; a light cued the lever providing the
next reinforcer. In the next condition, the light cue was removed and reinforcer
assignment strictly alternated between levers. The next two conditions
redetermined, in order, the first two conditions. Preference pulses, defined as a
tendency for relative response rate to decline to the just-reinforced alternative
with time since reinforcement, only appeared during the extinction schedule.
Although the pulse's functional form was well described by a reinforcer-induction
equation, there was a large residual between actual data and a pulse-as-artifact
simulation (McLean, Grace, Pitts, & Hughes, 2014) used to discern reinforcer
dependent contributions to pulsing. However, if that simulation was modified to
include a win-stay tendency (a propensity to stay on the just-reinforced
alternative), the residual was greatly reduced. Additional modifications of the
parameter values of the pulse-as-artifact simulation enabled it to accommodate
the present results as well as those it originally accommodated. In its revised
form, this simulation was used to create a model that describes response runs to
the preferred alternative as terminating probabilistically, and runs to the
unpreferred alternative as punctate with occasional perseverative response runs.
After reinforcement, choices are modeled as returning briefly to the lever
location that had been just reinforced. This win-stay propensity is hypothesized
as due to reinforcer induction.
PMID- 26420768
TI - Impact of the AYA HOPE Comorbidity Index on Assessing Health Care Service Needs
and Health Status among Adolescents and Young Adults with Cancer.
AB - BACKGROUND: Existing comorbidity indices were not developed for adolescent and
young adults (AYA) 15 to 39 years of age. The aim of this study was to assess
impact of comorbidities on health care service needs and health status among AYA
cancer survivors using the newly developed AYA HOPE comorbidity index in
comparison with the existing indices. METHODS: Data on comorbid conditions were
obtained from medical records and service needs and health status were from a
survey of AYA cancer survivors. Prevalence of comorbidities was based on the AYA
HOPE index. Charlson and NCI indices were compared. Multivariable logistic
regression was used. RESULTS: Of the 485 patients, 14.6% had >=2 comorbidities
based on the AYA HOPE Index. Prevalence of mental illness and obesity/overweight,
which were not included in existing indices, were 8.2% and 5.8%, respectively.
Prevalence of cardiovascular, endocrine, gastrointestinal, and neurologic
conditions were higher with the AYA HOPE Index than the other two indices. Forty
percent of AYA patients reported service needs, particularly for mental health
services (25.2%) and support groups (17.7%). Having >=2 comorbidities on the AYA
index was associated with higher mental health service needs [OR, 2.05; 95%
confidence interval (CI), 1.10-3.82] adjusting for demographic and clinical
factors. Comorbidities were associated with fair/poor self-reported health
status. CONCLUSION: The AYA HOPE Index is a more comprehensive comorbidity index
for AYA cancer patients than existing indices, and the number of comorbidities is
associated with service needs and health status. IMPACT: The AYA HOPE index could
identify patients' additional service needs early in therapy.
PMID- 26420770
TI - Effectiveness of individualised intervention on older residents with constipation
in nursing home: a randomised controlled trial.
AB - AIMS AND OBJECTIVES: To develop and examine the effectiveness of individualised
intervention to reduce constipation among older adults in nursing homes.
BACKGROUND: In long-term care facilities, approximately 60-80% of the residents
have symptoms of constipation. Constipation may lead to haemorrhoids, faecal
impaction, ulcers, intestinal bleeding and can also lead to a decrease in quality
of life. Although a high prevalence of constipation in older adults can be seen,
there is a lack of empirical evidence for delivering interventions based on
individual risk factors of constipation. Many factors cause constipation but the
risk factors are different for each individual. DESIGN: A prospective, randomised
control trial conducted in northern Taiwan. METHODS: Nursing home residents (n =
43) were randomly assigned to either the control group or the experimental group.
The control group received no extra care from the researcher while the
experimental group received an individualised intervention and an eight-week
follow-up. Participants were assessed using the Bristol Stool Form Scale, the
Patient Assessment of Constipation Symptoms, types and dosages of laxative, and
bowel sound observations. Data were taken at baseline, four weeks as well as
eight weeks after the intervention. RESULTS: The participants in the experimental
group had a significantly higher increase in the frequency of defecation (group
effect, p = 0.029) and in bowel sounds (interaction effect, p = 0.010) compared
to those in the control group. However, the two groups did not differ
significantly in symptoms and the severity of the constipation symptoms, Bristol
Stool Form and use of laxatives. CONCLUSIONS: The results of this trial suggest
that the individualised intervention may be appropriate for decreasing
constipation among nursing home residents and encourage further study and
confirmation. RELEVANCE TO CLINICAL PRACTICE: Using individualised intervention
to enhance the self-care ability related to constipation among older adults is
recommended.
PMID- 26420771
TI - Recording casualties of war.
PMID- 26420772
TI - Occurrence and severity of enamel decalcification adjacent to bracket bases and
sub-bracket lesions during orthodontic treatment with two different lingual
appliances.
AB - BACKGROUND: Using lingual enamel surfaces for bracket placement not only has
esthetic advantages, but may also be suitable in terms of reducing frequencies of
enamel decalcifications. OBJECTIVE: To test the null-hypothesis that there is no
significant difference in enamel decalcification or cavitation incidence adjacent
to and beneath bracket bases between two lingual multi-bracket (MB) appliances
that are different in terms of design, material composition, and manufacturing
technology (group A: WIN, DW-LingualSystems; group B: Incognito, 3M-Unitek),
taking into account patient- and treatment-related variables on white spot lesion
(WSL) formation. METHODS: Standardized, digital, top-view photographs of 630
consecutive subjects (16214 teeth; n Incognito = 237/6076 teeth; n WIN =
393/10138 teeth; mean age: 17.47+/-7.8; m/f 43.2/56.8%) with completed lingual MB
treatment of the upper and lower permanent teeth 1-7 were screened for
decalcification or cavitation adjacent to and beneath the bracket bases before
and after treatment, scored from 0 to 7. Non-parametric ANOVA was used for main
effects 'appliance type', 'gender', 'treatment complexity', 'grouped age'
(<=16/>16 years), and 'treatment duration' as covariable, at an alpha-level of
5%. RESULTS: About 2.57% [5.94%] of all teeth in group A [B] developed
decalcifications. Subject-related incidence was 9.59% [16.17%] for upper incisors
in group A [B], and 12.98% [25.74%] for all teeth 16-46. There were significant
effects by gender, age, and treatment duration. CONCLUSION: The null-hypothesis
was rejected: sub-bracket lesions were significantly less frequent in group A,
while frequencies of WSL adjacent to brackets were not significantly affected by
appliance type. In view of the overall low incidences of lingual post-orthodontic
white-spot lesions, the use of lingual appliances is advocated as a valid
strategy for a reduction of enamel decalcifications during orthodontic treatment.
PMID- 26420773
TI - Brachioplasty: A Personal Approach.
AB - Brachioplasty has become one of the most rapidly growing operations in plastic
surgery. There are a variety of arm presentations, due to either weight loss or
other reasons, and the extent of the defect can carry into the lateral chest wall
and the back. In this featured operative technique article, the author describes
indications, patient selection, and criteria for classifying brachioplasty, and
illustrates the surgical techniques of this procedure. Markings, scar
positioning, and the various operative steps are described along with the
intricacies of postoperative care, including scar control. A personal experience,
along with the limitations of brachioplasty, are discussed.
PMID- 26420774
TI - Challenging Breast Augmentations: The Influence of Preoperative Anatomical
Features on the Final Result.
AB - BACKGROUND: Achieving satisfactory results may be difficult in augmentation
mammaplasty patients in the presence of breast, chest wall, or vertebral
deformities. These deformities have not been classified previously, and the
impact of each deformity or combination of deformities has not been defined.
OBJECTIVES: The aims of this study are to determine the complicating factors in
augmentation mammaplasty, to classify these factors according to their influence
on surgical outcome, and to develop an identification system for simplifying the
recognition of challenging cases. METHODS: We retrospectively analyzed
photographs and records of 100 consecutive patients who underwent augmentation
mammaplasty. We observed suboptimal results in 18 cases. Preoperative deformities
of the breast, chest wall, and vertebra were recorded in order to determine which
factor or factors had complicated the surgeries. Eventually, the relationship
between suboptimal surgical results and complicating factors was evaluated.
RESULTS: We observed that some deformities alone caused suboptimal results,
whereas others did not. Deformities that caused suboptimal results alone were
called major complicating factors, and any others were called minor complicating
factors. We observed that suboptimal results were also obtained in patients who
had four minor complicating factors. Patients who had suboptimal results because
of major or minor complicating factors were considered challenging cases.
CONCLUSIONS: In this study, complicating factors for augmentation mammaplasty
were defined and classified as major or minor depending on their effect on the
surgical outcome. We suggest an identification system that simplifies the
recognition of challenging cases in breast augmentation.
PMID- 26420775
TI - A Personal Computer Freeware as a Tool for Surgeons to Plan Liver Resections.
AB - BACKGROUND AND AIMS: The increase in liver surgery and the proportion of
resections done on the margin to postoperative liver failure make preoperative
calculations regarding liver volume important. Earlier studies have shown good
correlation between calculations done with ImageJ and specimen weight as well as
volume calculations done with more robust systems. The correlation to actual
volumes of resected liver tissue has not been investigated, and this was the aim
of this study. MATERIAL AND METHODS: A total of 30 patients undergoing well
defined liver resections were included in this study. Volumes calculated with
ImageJ were compared to volume measurements done after the retrieval of resected
liver tissue. RESULTS AND CONCLUSIONS: A strong correlation between calculated
and measured liver volume was found with sample concordance correlation
coefficient (rhoc) = 0.9950. The knowledge on the nature of liver resections sets
liver surgeons in a unique position to be able to accurately predict the volumes
to be resected and, therefore, also the volume that will remain after surgery.
This becomes increasingly important with the evolvement of methods to extend the
boundaries of liver surgery. ImageJ is a reliable tool to preoperatively assess
liver volume.
PMID- 26420776
TI - Use of inhaled corticosteroids for the prevention and/or treatment of
bronchopulmonary dysplasia in preterm infants: a systematic review protocol.
AB - BACKGROUND: Inhaled steroids have been studied for both prevention and treatment
of bronchopulmonary dysplasia (BPD). Results have been inconsistent. Recently, a
large randomized controlled trial (RCT) has been reported. METHODS/DESIGN: We
will perform a comprehensive systematic literature search for randomized and
quasi-randomized controlled trials that studied the efficacy and safety of
inhaled corticosteroids administered to preterm infants (22-36 weeks) for either
the prevention or treatment of BPD diagnosed by both clinical and physiological
outcome criteria. We will assess potential risk of bias for each RCT meeting our
selection criteria using the Cochrane risk of bias tool for RCTs. The primary
outcome of interest will be mortality or BPD or both at 28 days postnatal age or
36 weeks postmenstrual age. Pooled estimates will be calculated using RevMan
software with a random effects model as primary analysis. We will assess the
quality of evidence using the Grading of Recommendations Assessment, Development
and Evaluation (GRADE) approach. DISCUSSION: Meta-analytic estimates of eligible
RCTs, potentially including a new large RCT, may significantly influence neonatal
practice in the prevention and treatment of respiratory problems in preterm
infants. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019628.
PMID- 26420777
TI - Current Usage of Traditional Chinese Medicine in the Management of Breast Cancer:
A Practitioner's Perspective.
AB - Introduction This qualitative study seeks to explore the role within the context
of Australian breast cancer oncology treatments that traditional Chinese medicine
(TCM) practitioners play in the treatment of breast cancer. Methods
Semistructured interviews were used on 2 groups: the first group was TCM
practitioners who were recognized experts in breast cancer, and the second group
consisted of TCM practitioners who treated breast cancer as part of their
practice but were not recognized experts. Data analysis was achieved through
grounded theory with open coding. Results The main themes reported on here are
the following: the role of TCM in the biomedical management of breast cancer, TCM
strategies for the management of breast cancer, and the perceived holistic
approach of the TCM practitioner and the importance of a TCM diagnosis in the
role of breast cancer care. Discussion The role of TCM in biomedical breast
cancer management is a supportive one; however, this role is difficult as there
is a lack of understanding of TCM by biomedical practitioners. The viewpoints of
practitioners differed on key strategies of TCM: diagnosis, and treatment
protocols. Patients sought the holistic approach of TCM practitioners as they
felt it addressed all aspects of their health and not just the symptoms relating
to breast cancer. Conclusion The lack of an integrated medicine approach in
relation to TCM makes it difficult to demonstrate the value of the contribution
TCM can make to biomedicine in the field of breast care oncology. Effectiveness
studies are needed that can accurately represent TCM in this field.
PMID- 26420778
TI - The Effectiveness of Group Intervention on Enhancing Cognitive Emotion Regulation
Strategies in Breast Cancer Patients: A 2-Year Follow-up.
AB - Purpose To evaluate the long-term effect of group intervention on enhancing
cognitive emotion regulation (CER) strategies in female patients with early-stage
breast cancer. Methods The sample included 174 patients who were diagnosed with
early-to-mid stage breast cancer, completed adjuvant therapy, and agreed to fill
out demographic and cognitive emotion regulation questionnaires (CERQ). About
half of the patients (86, 49.4%) chose to participate in an 8-session group
intervention (intervention group) while the others (88, 50.6%) did not
(comparison group). The structured intervention for enhancing coping strategies
with special emphasis on emotion regulation was conducted at the oncology unit at
Rabin Medical Center by 2 experienced therapists. Preliminary effects on CER
evaluated 6, 12, and 24 months postintervention were compared to the CER of a
group of patients that opted not to participate in the group intervention.
Results In the intervention group, the long-term effect (from baseline to 24
months) was assessed using the mix models module. Significant interaction effects
were found for both the Negative CER scales (F(3, 268 ,404) = 3.66, P = .01) and
for the Positive CER scales (F(3, 271 ,660) = 5.12, P = .002). No statistically
significant differences in socio-demographic characteristics and medical
variables were observed between the intervention and comparison groups.
Conclusion Our findings indicate that a group intervention aimed at empowerment
of coping strategies had positive long-term outcomes that reinforce adaptive
coping strategies and improve less effective strategies of cognitive emotion
regulation.
PMID- 26420779
TI - Bayesian multi-scale modeling for aggregated disease mapping data.
AB - In disease mapping, a scale effect due to an aggregation of data from a finer
resolution level to a coarser level is a common phenomenon. This article
addresses this issue using a hierarchical Bayesian modeling framework. We propose
four different multiscale models. The first two models use a shared random effect
that the finer level inherits from the coarser level. The third model assumes two
independent convolution models at the finer and coarser levels. The fourth model
applies a convolution model at the finer level, but the relative risk at the
coarser level is obtained by aggregating the estimates at the finer level. We
compare the models using the deviance information criterion (DIC) and Watanabe
Akaike information criterion (WAIC) that are applied to real and simulated data.
The results indicate that the models with shared random effects outperform the
other models on a range of criteria.
PMID- 26420780
TI - The digital revolution in phenotyping.
AB - Phenotypes have gained increased notoriety in the clinical and biological domain
owing to their application in numerous areas such as the discovery of disease
genes and drug targets, phylogenetics and pharmacogenomics. Phenotypes, defined
as observable characteristics of organisms, can be seen as one of the bridges
that lead to a translation of experimental findings into clinical applications
and thereby support 'bench to bedside' efforts. However, to build this
translational bridge, a common and universal understanding of phenotypes is
required that goes beyond domain-specific definitions. To achieve this ambitious
goal, a digital revolution is ongoing that enables the encoding of data in
computer-readable formats and the data storage in specialized repositories, ready
for integration, enabling translational research. While phenome research is an
ongoing endeavor, the true potential hidden in the currently available data still
needs to be unlocked, offering exciting opportunities for the forthcoming years.
Here, we provide insights into the state-of-the-art in digital phenotyping, by
means of representing, acquiring and analyzing phenotype data. In addition, we
provide visions of this field for future research work that could enable better
applications of phenotype data.
PMID- 26420782
TI - Anisotropy of Human Horizontal and Vertical Navigation in Real Space: Behavioral
and PET Correlates.
AB - Spatial orientation was tested during a horizontal and vertical real navigation
task in humans. Video tracking of eye movements was used to analyse the
behavioral strategy and combined with simultaneous measurements of brain
activation and metabolism ([18F]-FDG-PET). Spatial navigation performance was
significantly better during horizontal navigation. Horizontal navigation was
predominantly visually and landmark-guided. PET measurements indicated that
glucose metabolism increased in the right hippocampus, bilateral retrosplenial
cortex, and pontine tegmentum during horizontal navigation. In contrast, vertical
navigation was less reliant on visual and landmark information. In PET, vertical
navigation activated the bilateral hippocampus and insula. Direct comparison
revealed a relative activation in the pontine tegmentum and visual cortical areas
during horizontal navigation and in the flocculus, insula, and anterior cingulate
cortex during vertical navigation. In conclusion, these data indicate a
functional anisotropy of human 3D-navigation in favor of the horizontal plane.
There are common brain areas for both forms of navigation (hippocampus) as well
as unique areas such as the retrosplenial cortex, visual cortex (horizontal
navigation), flocculus, and vestibular multisensory cortex (vertical navigation).
Visually guided landmark recognition seems to be more important for horizontal
navigation, while distance estimation based on vestibular input might be more
relevant for vertical navigation.
PMID- 26420781
TI - Recent Advances and Emerging Applications in Text and Data Mining for Biomedical
Discovery.
AB - Precision medicine will revolutionize the way we treat and prevent disease. A
major barrier to the implementation of precision medicine that clinicians and
translational scientists face is understanding the underlying mechanisms of
disease. We are starting to address this challenge through automatic approaches
for information extraction, representation and analysis. Recent advances in text
and data mining have been applied to a broad spectrum of key biomedical questions
in genomics, pharmacogenomics and other fields. We present an overview of the
fundamental methods for text and data mining, as well as recent advances and
emerging applications toward precision medicine.
PMID- 26420783
TI - Basal Ganglia Activity Mirrors a Benefit of Action and Reward on Long-Lasting
Event Memory.
AB - The expectation of reward is known to enhance a consolidation of long-term memory
for events. We tested whether this effect is driven by positive valence or action
requirements tied to expected reward. Using a functional magnetic resonance
imaging (fMRI) paradigm in young adults, novel images predicted gain or loss
outcomes, which in turn were either obtained or avoided by action or inaction.
After 24 h, memory for these images reflected a benefit of action as well as a
congruence of action requirements and valence, namely, action for reward and
inaction for avoidance. fMRI responses in the hippocampus, a region known to be
critical for long-term memory function, reflected the anticipation of inaction.
In contrast, activity in the putamen mirrored the congruence of action
requirement and valence, whereas other basal ganglia regions mirrored overall
action benefits on long-lasting memory. The findings indicate a novel type of
functional division between the hippocampus and the basal ganglia in the
motivational regulation of long-term memory consolidation, which favors
remembering events that are worth acting for.
PMID- 26420784
TI - Characterizing VIP Neurons in the Barrel Cortex of VIPcre/tdTomato Mice Reveals
Layer-Specific Differences.
AB - Neocortical GABAergic interneurons have a profound impact on cortical circuitry
and its information processing capacity. Distinct subgroups of inhibitory
interneurons can be distinguished by molecular markers, such as parvalbumin,
somatostatin, and vasoactive intestinal polypeptide (VIP). Among these, VIP
expressing interneurons sparked a substantial interest since these neurons seem
to operate disinhibitory circuit motifs found in all major neocortical areas.
Several of these recent studies used transgenic Vip-ires-cre mice to specifically
target the population of VIP-expressing interneurons. This makes it necessary to
elucidate in detail the sensitivity and specificity of Cre expression for VIP
neurons in these animals. Thus, we quantitatively compared endogenous tdTomato
with Vip fluorescence in situ hybridization and alphaVIP immunohistochemistry in
the barrel cortex of VIPcre/tdTomato mice in a layer-specific manner. We show
that VIPcre/tdTomato mice are highly sensitive and specific for the entire
population of VIP-expressing neurons. In the barrel cortex, approximately 13% of
all GABAergic neurons are VIP expressing. Most VIP neurons are found in layer
II/III (~60%), whereas approximately 40% are found in the other layers of the
barrel cortex. Layer II/III VIP neurons are significantly different from VIP
neurons in layers IV-VI in several morphological and membrane properties, which
suggest layer-dependent differences in functionality.
PMID- 26420785
TI - Procedural Factors That Affect Psychophysical Measures of Spatial Selectivity in
Cochlear Implant Users.
AB - Behavioral measures of spatial selectivity in cochlear implants are important
both for guiding the programing of individual users' implants and for the
evaluation of different stimulation methods. However, the methods used are
subject to a number of confounding factors that can contaminate estimates of
spatial selectivity. These factors include off-site listening, charge
interactions between masker and probe pulses in interleaved masking paradigms,
and confusion effects in forward masking. We review the effects of these
confounds and discuss methods for minimizing them. We describe one such method in
which the level of a 125-pps masker is adjusted so as to mask a 125-pps probe,
and where the masker and probe pulses are temporally interleaved. Five
experiments describe the method and evaluate the potential roles of the different
potential confounding factors. No evidence was obtained for off-site listening of
the type observed in acoustic hearing. The choice of the masking paradigm was
shown to alter the measured spatial selectivity. For short gaps between masker
and probe pulses, both facilitation and refractory mechanisms had an effect on
masking; this finding should inform the choice of stimulation rate in interleaved
masking experiments. No evidence for confusion effects in forward masking was
revealed. It is concluded that the proposed method avoids many potential
confounds but that the choice of method should depend on the research question
under investigation.
PMID- 26420786
TI - Prevalence and compensation of academic leaders, professors, and trustees on
publicly traded US healthcare company boards of directors: cross sectional study.
AB - OBJECTIVE: To identify the prevalence, characteristics, and compensation of
members of the boards of directors of healthcare industry companies who hold
academic appointments as leaders, professors, or trustees. DESIGN: Cross
sectional study. SETTING: US healthcare companies publicly traded on the NASDAQ
or New York Stock Exchange in 2013. PARTICIPANTS: 3434 directors of
pharmaceutical, biotechnology, medical equipment and supply, and healthcare
provider companies. MAIN OUTCOME MEASURES: Prevalence, annual compensation, and
beneficial stock ownership of directors with affiliations as leaders, professors,
or trustees of academic medical and research institutions. RESULTS: 446
healthcare companies met the study search criteria, of which 442 (99%) had
publicly accessible disclosures on boards of directors. 180 companies (41%) had
one or more academically affiliated directors. Directors were affiliated with 85
geographically diverse non-profit academic institutions, including 19 of the top
20 National Institute of Health funded medical schools and all of the 17 US News
honor roll hospitals. Overall, these 279 academically affiliated directors
included 73 leaders, 121 professors, and 85 trustees. Leaders included 17 chief
executive officers and 11 vice presidents or executive officers of health systems
and hospitals; 15 university presidents, provosts, and chancellors; and eight
medical school deans or presidents. The total annual compensation to academically
affiliated directors for their services to companies was $54,995,786
(L35,836,000; ?49,185,900) (median individual compensation $193,000) and
directors beneficially owned 59,831,477 shares of company stock (median 50,699
shares). CONCLUSIONS: A substantial number and diversity of academic leaders,
professors, and trustees hold directorships at US healthcare companies, with
compensation often approaching or surpassing common academic clinical salaries.
Dual obligations to for profit company shareholders and non-profit clinical and
educational institutions pose considerable personal, financial, and institutional
conflicts of interest beyond that of simple consulting relationships. These
conflicts have not been fully addressed by professional societies or academic
institutions and deserve additional review, regulation, and, in some cases,
prohibition when conflicts cannot be reconciled.
PMID- 26420787
TI - Coupling Laser Diode Thermal Desorption with Acoustic Sample Deposition to
Improve Throughput of Mass Spectrometry-Based Screening.
AB - The move toward label-free screening in drug discovery has increased the demand
for mass spectrometry (MS)-based analysis. Here we investigated the approach of
coupling acoustic sample deposition (ASD) with laser diode thermal desorption
(LDTD)-tandem mass spectrometry (MS/MS). We assessed its use in a cytochrome P450
(CYP) inhibition assay, where a decrease in metabolite formation signifies CYP
inhibition. Metabolite levels for 3 CYP isoforms were measured as CYP3A4-1'-OH
midazolam, CYP2D6-dextrorphan, and CYP2C9-4'-OH-diclofenac. After incubation,
samples (100 nL) were acoustically deposited onto a stainless steel 384-LazWell
plate, then desorbed by an infrared laser directly from the plate surface into
the gas phase, ionized by atmospheric pressure chemical ionization (APCI), and
analyzed by MS/MS. Using this method, we achieved a sample analysis speed of 2.14
s/well, with bioanalytical performance comparable to the current online solid
phase extraction (SPE)-based MS method. An even faster readout speed was achieved
when postreaction sample multiplexing was applied, where three reaction samples,
one for each CYP, were transferred into the same well of the LazWell plate. In
summary, LDTD coupled with acoustic sample deposition and multiplexing
significantly decreased analysis time to 0.7 s/sample, making this MS-based
approach feasible to support high-throughput screening (HTS) assays.
PMID- 26420788
TI - Development of a Highly Sensitive Cell-Based Assay for Detecting Botulinum
Neurotoxin Type A through Neural Culture Media Optimization.
AB - Botulinum neurotoxin (BoNT) is the most lethal naturally produced neurotoxin. Due
to the extreme toxicity, BoNTs are implicated in bioterrorism, while the specific
mechanism of action and long-lasting effect was found to be medically applicable
in treating various neurological disorders. Therefore, for both public and
patient safety, a highly sensitive, physiologic, and specific assay is needed. In
this paper, we show a method for achieving a highly sensitive cell-based assay
for BoNT/A detection using the motor neuron-like continuous cell line NG108-15.
To achieve high sensitivity, we performed a media optimization study evaluating
three commercially available neural supplements in combination with retinoic
acid, purmorphamine, transforming growth factor beta1 (TGFbeta1), and ganglioside
GT1b. We found nonlinear combinatorial effects on BoNT/A detection sensitivity,
achieving an EC50 of 7.4 U +/- 1.5 SD (or ~7.9 pM). The achieved detection
sensitivity is comparable to that of assays that used primary and stem cell
derived neurons as well as the mouse lethality assay.
PMID- 26420789
TI - Global poplar root and leaf transcriptomes reveal links between growth and stress
responses under nitrogen starvation and excess.
AB - Nitrogen (N) starvation and excess have distinct effects on N uptake and
metabolism in poplars, but the global transcriptomic changes underlying
morphological and physiological acclimation to altered N availability are
unknown. We found that N starvation stimulated the fine root length and surface
area by 54 and 49%, respectively, decreased the net photosynthetic rate by 15%
and reduced the concentrations of NH4+, NO3(-) and total free amino acids in the
roots and leaves of Populus simonii Carr. in comparison with normal N supply,
whereas N excess had the opposite effect in most cases. Global transcriptome
analysis of roots and leaves elucidated the specific molecular responses to N
starvation and excess. Under N starvation and excess, gene ontology (GO) terms
related to ion transport and response to auxin stimulus were enriched in roots,
whereas the GO term for response to abscisic acid stimulus was overrepresented in
leaves. Common GO terms for all N treatments in roots and leaves were related to
development, N metabolism, response to stress and hormone stimulus. Approximately
30-40% of the differentially expressed genes formed a transcriptomic regulatory
network under each condition. These results suggest that global transcriptomic
reprogramming plays a key role in the morphological and physiological acclimation
of poplar roots and leaves to N starvation and excess.
PMID- 26420790
TI - Waterlogging in late dormancy and the early growth phase affected root and leaf
morphology in Betula pendula and Betula pubescens seedlings.
AB - The warmer winters of the future will increase snow-melt frequency and rainfall,
thereby increasing the risk of soil waterlogging and its effects on trees in
winter and spring at northern latitudes. We studied the morphology of roots and
leaves of 1-year-old silver birch (Betula pendula Roth) and pubescent birch
(Betula pubescens Ehrh.) seedlings exposed to waterlogging during dormancy or at
the beginning of the growing season in a growth-chamber experiment. The
experiment included 4-week dormancy (Weeks 1-4), a 4-week early growing season
(Weeks 5-8) and a 4-week late growing season (Weeks 9-12). The treatments were:
(i) no waterlogging, throughout the experiment ('NW'); (ii) 4-week waterlogging
during dormancy (dormancy waterlogging 'DW'); (iii) 4-week waterlogging during
the early growing season (growth waterlogging 'GW'); and (iv) 4-week DW followed
by 4-week GW during the early growing season ('DWGW'). Dormancy waterlogging
affected the roots of silver birch and GW the roots and leaf characteristics of
both species. Leaf area was reduced in both species by GW and DWGW. In pubescent
birch, temporarily increased formation of thin roots was seen in root systems of
GW seedlings, which suggests an adaptive mechanism with respect to excess soil
water. Additionally, the high density of non-glandular trichomes and their
increase in DWGW leaves were considered possible morphological adaptations to
excess water in the soil, as was the constant density of stem lenticels during
stem-diameter growth. The higher density in glandular trichomes of DWGW silver
birch suggests morphological acclimation in that species. The naturally low
density of non-glandular trichomes, low density of stem lenticels in waterlogged
seedlings and decrease in root growth seen in DWGW and DW silver birch seedlings
explain, at least partly, why silver birch grows more poorly relative to
pubescent birch in wet soils.
PMID- 26420791
TI - The influence of the soil on spring and autumn phenology in European beech.
AB - Tree phenology is a key discipline in forest ecology linking seasonal
fluctuations of photoperiod and temperature with the annual development of buds,
leaves and flowers. Temperature and photoperiod are commonly considered as main
determinants of tree phenology while little is known about interactions with soil
chemical characteristics. Seedlings of 12 European beech (Fagus sylvatica L.)
provenances were transplanted in 2011 to model ecosystems and grown for 4 years
on acidic or calcareous forest soil. Spring bud burst and autumnal leaf
senescence were assessed in the last 2 years, 2013 and 2014, which were
characterized by contrasting annual temperatures with a very warm spring and
autumn in 2014. In 2013, spring bud burst and autumnal leaf senescence were
advanced on acidic soil with a greater effect on leaf senescence. Hence, the
vegetation period 2013 was shorter on this soil type compared with that on
calcareous soil. In 2014, a similar soil effect was observed for spring bud burst
while autumnal leaf senescence and the length of the vegetation period were not
affected, probably due to interferences with the overall extension of the
vegetation period in this exceptionally warm year. A different soil
responsiveness was observed among the provenances with early bursting or
senescing provenances being more sensitive than late bursting or senescing
provenances. The findings of this study highlight the soil as an ecologically
relevant factor in tree phenology and might help explain existing uncertainties
in current phenology models.
PMID- 26420792
TI - Populus species from diverse habitats maintain high night-time conductance under
drought.
AB - We investigated the interspecific variability in nocturnal whole-plant stomatal
conductance under well-watered and drought conditions in seedlings of four
species of Populus from habitats characterized by abundant water supply (mesic
and riparian) or from drier upland sites. The study was carried out to determine
whether (i) nocturnal conductance varies across different species of Populus
according to their natural habitat, (ii) nocturnal conductance is affected by
water stress similarly to daytime conductance based on species habitat and (iii)
differences in conductance among species could be explained partly by differences
in stomatal traits. We measured whole-plant transpiration and conductance (G) of
greenhouse-grown seedlings using an automated high-resolution gravimetric
technique. No relationship was found between habitat preference and daytime G
(GD), but night-time G (GN) was on average 1.5 times higher in riparian and mesic
species (P. deltoides Bartr. ex Marsh. and P. trichocarpa Torr. & Gray) than in
those from drier environments (P. tremuloides Michx. and P. * petrowskyana
Schr.). GN was not significantly reduced under drought in riparian species.
Upland species restricted GN significantly in response to drought, but it was
still at least one order of magnitude greater that the cuticular conductance
until leaf death was imminent. Under both well-watered and drought conditions, GN
declined with increasing vapour pressure deficit (D). Also, a small increase in
GN towards the end of the night period was observed in P. deltoides and P. *
petrowskyana, suggesting the involvement of endogenous regulation. The anatomical
analyses indicated a positive correlation between G and variable stomatal pore
index among species and revealed that stomata are not likely to be leaky but
instead seem capable of complete occlusion, which raises the question of the
possible physiological role of the significant GN observed under drought. Further
comparisons among closely related species that occupy ecologically diverse
habitats may provide a better understanding of the genetic versus environmental
regulations of nocturnal water loss.
PMID- 26420793
TI - Phosphorus and nitrogen physiology of two contrasting poplar genotypes when
exposed to phosphorus and/or nitrogen starvation.
AB - Phosphorus (P) and nitrogen (N) are the two essential macronutrients for tree
growth and development. To elucidate the P and N physiology of woody plants
during acclimation to P and/or N starvation, we exposed saplings of the slow
growing Populus simonii Carr (Ps) and the fast-growing Populus * euramericana
Dode (Pe) to complete nutrients or starvation of P, N or both elements (NP). P. *
euramericana had lower P and N concentrations and greater P and N amounts due to
higher biomass production, thereby resulting in greater phosphorus use
efficiency/N use efficiency (PUE/NUE) compared with Ps. Compared with the roots
of Ps, the roots of Pe exhibited higher enzymatic activities in terms of acid
phosphatases (APs) and malate dehydrogenase (MDH), which are involved in P
mobilization, and nitrate reductase (NR), glutamate synthase (GOGAT) and
glutamate dehydrogenase (GDH), which participate in N assimilation. The
responsiveness of the transcriptional regulation of key genes encoding
transporters for phosphate, ammonium and nitrate was stronger in Pe than in Ps.
These results suggest that Pe possesses a higher capacity for P/N uptake and
assimilation, which promote faster growth compared with Ps. In both poplars, P or
NP starvation caused significant decreases in the P concentrations and increases
in PUE. Phosphorus deprivation induced the activity levels of APs,
phosphoenolpyruvate carboxylase and MDH in both genotypes. Nitrogen or NP
deficiency resulted in lower N concentrations, amino acid levels, NR and GOGAT
activities, and higher NUE in both poplars. Thus, in Ps and Pe, the mRNA levels
of PHT1;5, PHT1;9, PHT2;1, AMT2;1 and NR increased in the roots, while PHT1;9,
PHO1;H1, PHO2, AMT1;1 and NRT2;1 increased in the leaves during acclimation to P,
N or NP deprivation. These results suggest that both poplars suppress P/N uptake,
mobilization and assimilation during acclimation to P, N or NP starvation.
PMID- 26420794
TI - Modification of the tree root electrical capacitance method under laboratory
conditions.
AB - For many years, scientists have been searching for nondestructive methods for the
measurement of plant root system parameters. The measurement of electrical
capacitance (EC) across the root has been proposed as one such nondestructive
method. This article presents a study on the determination of relationships
between EC measurement and the shape and size of the electrodes immersed in
medium that are used for measurement. Measurement of EC and the parameters
characterizing root systems of 1-year-old seedlings of the common beech Fagus
sylvatica L. was conducted under laboratory conditions. The measurements of EC
were performed between seedling root systems and two different electrodes in the
form of a cylinder or a rectangular plate. Statistically significant correlations
were found between the capacitance and root system parameters in both the
variants; however, the correlations were higher in the case of the flat
rectangular plate. Correlation coefficient (r) between EC and total root length
was 0.688 for cylindrical electrode and 0.802 for rectangular plate, for total
root area 0.641 and 0.818, and for dry weight of root system 0.502 and 0.747. The
best-fitted linear regression relationships between the EC and the measured
parameters were characterized by low determination coefficients in variants with
cylindrical electrodes, and higher with flat rectangular plate electrodes. The
results indicated that a two-dielectric media concept is a better model than
Dalton's model when attempting to interpret the behavior of root and soil
capacitance. The different electrodes probably allow root capacitance
measurements to be interpreted from different aspects. However, this hypothesis
requires further verification.
PMID- 26420795
TI - Evolutionary Divergence of Aggregatibacter actinomycetemcomitans.
AB - Gram-negative facultative Aggregatibacter actinomycetemcomitans is an oral
pathogen associated with periodontitis. The genetic heterogeneity among A.
actinomycetemcomitans strains has been long recognized. This study provides a
comprehensive genomic analysis of A. actinomycetemcomitans and the closely
related nonpathogenic Aggregatibacter aphrophilus. Whole genome sequencing by
Illumina MiSeq platform was performed for 31 A. actinomycetemcomitans and 2 A.
aphrophilus strains. Sequence similarity analysis shows a total of 3,220 unique
genes across the 2 species, where 1,550 are core genes present in all genomes and
1,670 are variable genes (accessory genes) missing in at least 1 genome.
Phylogenetic analysis based on 397 concatenated core genes distinguished A.
aphrophilus and A. actinomycetemcomitans. The latter was in turn divided into 5
clades: clade b (serotype b), clade c (serotype c), clade e/f (serotypes e and
f), clade a/d (serotypes a and d), and clade e' (serotype e strains). Accessory
genes accounted for 14.1% to 23.2% of the A. actinomycetemcomitans genomes, with
a majority belonging to the category of poorly characterized by Cluster of
Orthologous Groups classification. These accessory genes were often organized
into genomic islands (n = 387) with base composition biases, suggesting their
acquisitions via horizontal gene transfer. There was a greater degree of
similarity in gene content and genomic islands among strains within clades than
between clades. Strains of clade e' isolated from human were found to be missing
the genomic island that carries genes encoding cytolethal distending toxins.
Taken together, the results suggest a pattern of sequential divergence, starting
from the separation of A. aphrophilus and A. actinomycetemcomitans through gain
and loss of genes and ending with the divergence of the latter species into
distinct clades and serotypes. With differing constellations of genes, the A.
actinomycetemcomitans clades may have evolved distinct adaptation strategies to
the human oral cavity.
PMID- 26420796
TI - Gene set differential analysis of time course expression profiles via sparse
estimation in functional logistic model with application to time-dependent
biomarker detection.
AB - High-throughput time course expression profiles have been available in the last
decade due to developments in measurement techniques and devices. Functional data
analysis, which treats smoothed curves instead of originally observed discrete
data, is effective for the time course expression profiles in terms of dimension
reduction, robustness, and applicability to data measured at small and
irregularly spaced time points. However, the statistical method of differential
analysis for time course expression profiles has not been well established. We
propose a functional logistic model based on elastic net regularization (F
Logistic) in order to identify the genes with dynamic alterations in case/control
study. We employ a mixed model as a smoothing method to obtain functional data;
then F-Logistic is applied to time course profiles measured at small and
irregularly spaced time points. We evaluate the performance of F-Logistic in
comparison with another functional data approach, i.e. functional ANOVA test (F
ANOVA), by applying the methods to real and synthetic time course data sets. The
real data sets consist of the time course gene expression profiles for long-term
effects of recombinant interferon beta on disease progression in multiple
sclerosis. F-Logistic distinguishes dynamic alterations, which cannot be found by
competitive approaches such as F-ANOVA, in case/control study based on time
course expression profiles. F-Logistic is effective for time-dependent biomarker
detection, diagnosis, and therapy.
PMID- 26420798
TI - Acute Chagas Disease and Risk of Congenital Infection.
PMID- 26420797
TI - Group association test using a hidden Markov model.
AB - In the genomic era, group association tests are of great interest. Due to the
overwhelming number of individual genomic features, the power of testing for
association of a single genomic feature at a time is often very small, as are the
effect sizes for most features. Many methods have been proposed to test
association of a trait with a group of features within a functional unit as a
whole, e.g. all SNPs in a gene, yet few of these methods account for the fact
that generally a substantial proportion of the features are not associated with
the trait. In this paper, we propose to model the association for each feature in
the group as a mixture of features with no association and features with non-zero
associations to explicitly account for the possibility that a fraction of
features may not be associated with the trait while other features in the group
are. The feature-level associations are first estimated by generalized linear
models; the sequence of these estimated associations is then modeled by a hidden
Markov chain. To test for global association, we develop a modified likelihood
ratio test based on a log-likelihood function that ignores higher order
dependency plus a penalty term. We derive the asymptotic distribution of the
likelihood ratio test under the null hypothesis. Furthermore, we obtain the
posterior probability of association for each feature, which provides evidence of
feature-level association and is useful for potential follow-up studies. In
simulations and data application, we show that our proposed method performs well
when compared with existing group association tests especially when there are
only few features associated with the outcome.
PMID- 26420799
TI - Reply to Henao-Martinez, et al.
PMID- 26420800
TI - Early, Real-Time Medical Diagnosis of Botulism by Endopeptidase-Mass
Spectrometry.
AB - Botulinum toxin was detected in patient serum using Endopeptidase-mass
spectrometry assay, although all conventional tests provided negative results.
Antitoxin was administered, resulting in patient improvement. Implementing this
highly sensitive and rapid assay will improve preparedness for foodborne botulism
and deliberate exposure.
PMID- 26420801
TI - Influenza Vaccine Effectiveness in a Low-Income, Urban Community Cohort.
AB - In this community-based cohort study of 275 primarily low-income, urban
households in New York City, overall 2013-2014 influenza vaccine effectiveness
(VE) was 62.5% (95% confidence interval, 21.7%-82.0%). VE point estimates were
highest against 2009 H1N1 and for those who were vaccinated in 2013-2014 but not
in 2012-2013.
PMID- 26420803
TI - Contagious equine metritis cases reported in France since 2006.
PMID- 26420802
TI - Combined Directional Atherectomy and Drug-Eluting Balloon Angioplasty for
Isolated Popliteal Artery Lesions in Patients With Peripheral Artery Disease.
AB - PURPOSE: To evaluate the midterm results of combined directional atherectomy (DA)
and drug-eluting balloon (DEB) angioplasty for atherosclerotic lesions of the
popliteal artery. METHODS: In a single-arm, prospective study, 21 patients (mean
age 63+/-16 years; 16 men) with isolated popliteal artery lesions were enrolled
and underwent treatment with combined DA and DEB angioplasty under filter
protection between October 2009 and February 2014. The majority (18, 86%)
presented with lifestyle-limiting intermittent claudication and 3 with critical
limb ischemia. Fifteen (71%) target sites were de novo lesions; 4 were
occlusions. The main outcome was primary patency; secondary outcomes were
technical success, secondary patency, and early and midterm morbidity and
mortality. RESULTS: The TurboHawk atherectomy device was used in 15 (71%)
patients and the SilverHawk peripheral plaque excision system in the remaining 6
patients. The In.Pact Admiral/Pacific DEB was used in the majority of cases (15,
71%). The technical success rate was 90% (n=19). One flow-limiting dissection was
treated with bailout stenting. Complications included a perforation of the
popliteal artery and 2 puncture site hematomas; there was no distal embolic
event. The mean follow-up was 18+/-12 months. Two restenoses were retreated
successfully. Kaplan-Meier estimates of primary patency at 12 and 18 months were
95% and 90%, respectively; the secondary patency was 100%. One (5%) patient died
in follow-up. None of the patients had an amputation. CONCLUSION: In this
prospective single-arm study, the combined therapy of DA and DEB angioplasty for
popliteal artery lesions showed promising midterm performance. The combination of
DA and DEB may, in highly selected patients, overcome the challenges presented by
the mobility of the knee joint.
PMID- 26420804
TI - Reduction in daily milk yield associated with subclinical bovine herpesvirus 1
infection.
AB - The aim of this observational cohort study was to investigate the potential
economic impact of subclinical bovine herpesvirus 1 (BoHV-1) infection in a
commercial UK dairy herd in terms of milk yield depression. Infection status of
cows (infected or not infected) was assigned from serology on a single occasion.
A multi-level linear model was used to evaluate the impact of infection status on
milk production, using milk records that were routinely collected over two years.
BoHV-1 seropositive cows produced 2.6 kg/day less milk over the study period
compared with cows that were seronegative. This result highlights the importance
of appropriate management of risks associated with subclinical infection with
BoHV-1 as part of proactive herd health and production management.
PMID- 26420805
TI - Foreword.
PMID- 26420806
TI - Early childhood development and the social determinants of health inequities.
AB - Children's health and development outcomes follow a social gradient: the further
up the socioeconomic spectrum, the better the outcomes. Based upon a review of
multiple forms of evidence, and with a specific focus upon Australia, this
article investigates the causes of these socially produced inequities, their
impact upon health and development during the early years and what works to
reduce these inequities. Using VicHealth's Fair Foundations framework, we report
upon child health inequity at three different levels: the socioeconomic,
political and cultural level; daily living conditions; the individual health
related behaviours. Although intensive interventions may improve the absolute
conditions of significantly disadvantaged children and families, interventions
that have been shown to effectively reduce the gap between the best and worst off
families are rare. Numerous interventions have been shown to improve some aspect
of prenatal, postnatal, family, physical and social environments for young
children; however, sustainable or direct effects are difficult to achieve.
Inequitable access to services has the potential to maintain or increase
inequities during the early years, because those families most in need of
services are typically least able to access them. Reducing inequities during
early childhood requires a multi-level, multi-faceted response that incorporates:
approaches to governance and decision-making; policies that improve access to
quality services and facilitate secure, stable, flexible workplaces for parents;
service systems that reflect the characteristics of proportionate universalism,
function collaboratively, and deliver evidence-based programs in inclusive
environments; strong, supportive communities; and information and timely
assistance for parents so they feel supported and confident.
PMID- 26420807
TI - Social innovation for the promotion of health equity.
AB - The role of social innovations in transforming the lives of individuals and
communities has been a source of popular attention in recent years. This article
systematically reviews the available evidence of the relationship between social
innovation and its promotion of health equity. Guided by Fair Foundations: The
VicHealth framework for health equity and examining four types of social
innovation--social movements, service-related social innovations, social
enterprise and digital social innovations--we find a growing literature on social
innovation activities, but inconsistent evaluative evidence of their impacts on
health equities, particularly at the socio-economic, political and cultural level
of the framework. Distinctive characteristics of social innovations related to
the promotion of health equity include the mobilization of latent or unrealised
value through new combinations of (social, cultural and material) resources;
growing bridging social capital and purposeful approaches to linking individual
knowledge and experience to institutional change. These have implications for
health promotion practice and for research about social innovation and health
equity.
PMID- 26420808
TI - Addressing social determinants of health inequities through settings: a rapid
review.
AB - Changing settings to be more supportive of health and healthy choices is an
optimum way to improve population health and health equity. This article uses the
World Health Organisation's (1998) (WHO Health Promotion Glossary. WHO
Collaborating Centre for Health Promotion, Department of Public Health and
Community Medicine, University of Sydney, NSW) definition of settings approaches
to health promotion as those focused on modifying settings' structure and nature.
A rapid literature review was undertaken in the period June-August 2014,
combining a systematically conducted search of two major databases with targeted
searches. The review focused on identifying what works in settings approaches to
address the social determinants of health inequities, using Fair Foundations: the
VicHealth framework for health equity. This depicts the social determinants of
health inequities as three layers of influence, and entry points for action to
promote health equity. The evidence review identified work in 12 settings
(cities; communities and neighbourhoods; educational; healthcare; online; faith
based; sports; workplaces; prisons; and nightlife, green and temporary settings),
and work at the socioeconomic, political and cultural context layer of the Fair
Foundations framework (governance, legislation, regulation and policy). It
located a relatively small amount of evidence that settings themselves are being
changed in ways which address the social determinants of health inequities.
Rather, many initiatives focus on individual behaviour change within settings.
There is considerable potential for health promotion professionals to focus
settings work more upstream and so replace or integrate individual approaches
with those addressing daily living conditions and higher level structures, and a
significant need for programmes to be evaluated for differential equity impacts
and published to provide a more solid evidence base.
PMID- 26420809
TI - Fair Foundations for health equity.
PMID- 26420810
TI - Addressing inequities in alcohol consumption and related harms.
AB - Social determinants, or the conditions in which individuals are born, grow, live,
work and age, can result in inequities in health and well-being. However, to-date
little research has examined alcohol use and alcohol-related problems from an
inequities and social determinants perspective. This study reviewed the evidence
base regarding inequities in alcohol consumption and alcohol-related health
outcomes in Australia and identified promising approaches for promoting health
equity. Fair Foundations: the VicHealth framework for health equity was used as
an organizing schema. The review found that social determinants can strongly
influence inequities in alcohol consumption and related harms. In general, lower
socioeconomic groups experience more harm than wealthier groups with the same
level of alcohol consumption. While Australia has implemented numerous alcohol
related interventions and policies, most do not explicitly aim to reduce
inequities, and some may inadvertently exacerbate existing inequities.
Interventions with the greatest potential to decrease inequities in alcohol
consumption and alcohol-related harms include town planning, zoning and licensing
to prevent disproportionate clustering of outlets in disadvantaged areas;
interventions targeting licensed venues; and interventions targeting vulnerable
populations. Interventions that may worsen inequities include national
guidelines, technological interventions and public drinking bans. There is a need
for further research into the best methods for reducing inequities in alcohol
consumption and related harms.
PMID- 26420811
TI - Promoting equity in the mental wellbeing of children and young people: a scoping
review.
AB - There is increasing emphasis on wellbeing as a target for mental health
promotion, especially during the formative period of childhood. Despite growing
research on the importance of mental wellbeing, there is little information on
how to effectively promote it or how to promote it equitably. This article
presents a scoping review of interventions which seek to promote mental wellbeing
and reduce inequities in children and young people living in high income
countries. We used Fair Foundations: The VicHealth framework for health equity
(VicHealth (2013) Melbourne, Australia: The Victorian Health Promotion
Foundation) to identify points of entry at three layers of influence: (i)
socioeconomic, cultural and political contexts, (ii) daily living conditions, and
(iii) individual and family health-related factors. We identified more than 1000
interventions which aimed to prevent or treat childhood mental illness, but there
were far fewer that aimed to promote children's or young people's mental
wellbeing. The interventions we studied were either universal or specifically
targeted children from disadvantaged families: none explicitly used an equity
framework to guide their design or evaluation or addressed social gradients in
wellbeing. Most interventions remained focused on proximate factors, although we
also identified a handful of interventions that sought to address children's
access to services and their educational and neighbourhood environments. However,
we found encouraging evidence that interventions in family and educational
settings were successful in building children's strengths and supporting positive
parenting, universally and within disadvantaged groups. Such positive programme
evaluations signal the potential for using a proportionate universalism approach
that emphasizes equity in the promotion of mental wellbeing.
PMID- 26420812
TI - Addressing inequities in healthy eating.
AB - What, when, where and how much people eat is influenced by a complex mix of
factors at societal, community and individual levels. These influences operate
both directly through the food system and indirectly through political, economic,
social and cultural pathways that cause social stratification and influence the
quality of conditions in which people live their lives. These factors are the
social determinants of inequities in healthy eating. This paper provides an
overview of the current evidence base for addressing these determinants and for
the promotion of equity in healthy eating.
PMID- 26420813
TI - Tobacco control approaches and inequity--how far have we come and where are we
going?
AB - Despite Australia's success in reducing smoking rates, substantial inequities
persist--with high smoking prevalence among disadvantaged groups. This article
uses Fair Foundations: The VicHealth framework for health equity to identify
promising strategies for promoting equity within tobacco control policies and
programmes. A rapid review of the Australian and international literature was
conducted in March 2014 using Pubmed, ISI web of Science and Scopus, Cochrane
library and Google Scholar. A search of the grey literature was conducted to
identify promising policy interventions. Population health surveys suggest that
tobacco-related inequities in Victoria are beginning to decline. Data from the
Victorian Smoking Survey shows that the inequity gap is narrowing, and in recent
years, the prevalence of regular smoking declined fastest among disadvantaged
smokers. Future approaches to accelerate reductions in tobacco-related inequities
include: (i) continue proven population-based tobacco control policies-
especially increasing the price of tobacco (while remaining cognisant of the
increased economic burden for those smokers who do not quit), and continuing mass
media campaigns; (ii) strengthening social policies to promote equity in early
child development; educational experiences; quality of local environments;
employment and working conditions; (iii) identifying and investing in targeted
approaches to influence social norms and more effectively identify and support
disadvantaged smokers to quit; (iv) within tobacco control programmes, give
greatest priority to interventions focused on adult smokers (including pregnant
women and their partners).
PMID- 26420816
TI - Correction.
AB - In the article by Quintavalle et al (Quintavalle C, Anselmi CV, De Micco F,
Roscigno G, Visconti G, Golia B, Focaccio A, Ricciardelli B, Perna E, Papa L,
Donnarumma E, Condorelli G, Briguori C. Neutrophil gelatinase-associated
lipocalin and contrast-induced acute kidney injury. Circ Cardiovasc Interv.
2015;8:e002673. DOI: 10.1161/CIRCINTERVENTIONS.115.002673.), which published
online September 2, 2015, and appears in the September 2015 issue of the journal,
a correction was needed. On page 1, the institutional affiliation for Elvira
Donnarumma, PhD, "SDN Foundation," has been changed to read, "IRCCS SDN, Naples,
Italy." The institutional affiliation for Laura Papa, PhD, "Institute for
Endocrinology and Experimental Oncology, National Research Council, Naples,
Italy," has been changed to read, "Institute of Genetics and Biomedical Research,
Milan Unit, Milan, Italy" and "Humanitas Research Hospital, Rozzano, Italy." The
authors regret this error.
PMID- 26420814
TI - Biomarker-driven stratification of disease-risk in non-metastatic
medulloblastoma: Results from the multi-center HIT-SIOP-PNET4 clinical trial.
AB - PURPOSE: To improve stratification of risk-adapted treatment for non-metastatic
(M0), standard-risk medulloblastoma patients by prospective evaluation of
biomarkers of reported biological or prognostic significance, alongside clinico
pathological variables, within the multi-center HIT-SIOP-PNET4 trial. METHODS:
Formalin-fixed paraffin-embedded tumor tissues were collected from 338 M0
patients (>4.0 years at diagnosis) for pathology review and assessment of the WNT
subgroup (MBWNT) and genomic copy-number defects (chromosome 17, MYC/MYCN, 9q22
(PTCH1) and DNA ploidy). Clinical characteristics were reviewed centrally.
RESULTS: The favorable prognosis of MBWNT was confirmed, however better outcomes
were observed for non-MBWNT tumors in this clinical risk-defined cohort compared
to previous disease-wide clinical trials. Chromosome 17p/q defects were
heterogeneous when assessed at the cellular copy-number level, and predicted poor
prognosis when they occurred against a diploid (ch17(im)/diploid(cen)), but not
polyploid, genetic background. These factors, together with post-surgical tumor
residuum (R+) and radiotherapy delay, were supported as independent prognostic
markers in multivariate testing. Notably, MYC and MYCN amplification were not
associated with adverse outcome. In cross-validated survival models derived for
the clinical standard-risk (M0/R0) disease group, (ch17(im)/diploid(cen); 14% of
patients) predicted high disease-risk, while the outcomes of patients without
(ch17(im)/diploid(cen)) did not differ significantly from MBWNT, allowing re
classification of 86% as favorable-risk. CONCLUSIONS: Biomarkers, established
previously in disease-wide studies, behave differently in clinically-defined
standard-risk disease. Distinct biomarkers are required to assess disease-risk in
this group, and define improved risk-stratification models. Routine testing for
specific patterns of chromosome 17 imbalance at the cellular level, and MBWNT,
provides a strong basis for incorporation into future trials.
PMID- 26420815
TI - Efficacy and safety of capecitabine-based first-line chemotherapy in advanced or
metastatic breast cancer: a meta-analysis of randomised controlled trials.
AB - We sought to evaluate the efficacy and safety of capecitabine-based therapy as
first-line chemotherapy in advanced breast cancer. Randomised controlled trials
of capecitabine monotherapy or combined treatment were included in the meta
analysis. PubMed, EMBASE, the Cochrane Library database and important meeting
summaries were searched systematically. Outcomes were progression-free survival
(PFS), overall survival (OS), overall response rate (ORR) and grades 3-4 drug
related adverse events.Nine trials with 1798 patients were included. The results
indicated a significant improvement with capecitabine-based chemotherapy compared
with capecitabine-free chemotherapy in ORR (relative risk [RR] 1.14, 95%
confidence interval [CI] 1.03 to 1.26, P = 0.013) and PFS (hazard ratio [HR]
0.77, 95% CI 0.69 to 0.87, P < 0.0001). Overall survival favoured capecitabine
based chemotherapy, but this was not significant. There were more incidences of
neutropenia and neutropenic fever in the capecitabine-free chemotherapy group and
more vomiting, diarrhoea and hand-foot syndrome in the capecitabine-based
chemotherapy group. There were no significant differences in nausea, fatigue,
cardiotoxicity or mucositis/stomatitis between the two treatment
regimens.Capecitabine-based chemotherapy significantly improves ORR and PFS in
patients with advanced breast cancer, but has no demonstrable impact on OS.
Capecitabine-based regimens are suitable as first-line treatment for patients
with advanced breast cancer.
PMID- 26420817
TI - Predictors of unstable distal radius fractures: a systematic review and meta
analysis.
AB - The aim of this study was to perform a systematic review in order to identify
predictors of secondary displacement in distal radius fractures. We performed a
systematic review and identified all studies that reported secondary displacement
following distal radius fractures. Where possible, we pooled the odds ratios of
predictors. The initial search yielded 3178 studies of which 27 were included.
Multiple studies found that age, shortening, volar comminution, loss of radial
inclination, the presence of a volar hook, AO type 3 fractures (A3, B3, C3) and
the Older classification were significant predictors of secondary displacement.
Pooling revealed a significantly increased risk of secondary displacement in
fractures with dorsal comminution, in women and in patients aged >60 years. An
associated ulna fracture or intra-articular involvement does not result in an
increased risk of secondary displacement. The overview provided in this study can
help surgeons to inform patients of the chances of success of closed treatment
regarding the radiological outcome and facilitate shared decision making. LEVEL
OF EVIDENCE: II.
PMID- 26420818
TI - Safe use of MRI in people with cardiac implantable electronic devices.
AB - MR scanning in patients with cardiac implantable electronic devices (CIEDs) was
formerly felt to be contraindicated, but an increasing number of patients have an
implanted MR conditional device, allowing them to safely undergo MR scanning,
provided the manufacturer's guidance is adhered to. In addition, some patients
with non-MR conditional devices may undergo MR scanning if no other imaging
modality is deemed suitable and there is a clear clinical indication for scanning
which outweighs the potential risk. The following guidance has been formulated by
the British Heart Rhythm Society and endorsed by the British Cardiovascular
Society and others. It describes protocols that should be followed for patients
with CIEDs undergoing MR scanning. The recommendations, principles and
conclusions are supported by the Royal College of Radiologists.
PMID- 26420819
TI - Rac1 GTPase in pancreatic cancer.
PMID- 26420820
TI - Improving Anticoagulation Measurement Novel Warfarin Composite Measure.
AB - BACKGROUND: Percent time in therapeutic range (TTR) and international normalized
ratio (INR) variability both measure warfarin control and are associated with
outcomes independently. Here, we examine the advantages of a warfarin composite
measure (WCM), which summarizes the 2 when measuring patient outcomes. We also
examine how the measure chosen would affect anticoagulation clinic performance
rankings. METHODS AND RESULTS: We constructed WCM using an equally weighted
method, adding standardized TTR to standardized log-transformed INR variability
using 103 897 warfarin-experienced patients from 100 anticoagulation clinics. We
examined the association of WCM with ischemic stroke, major bleeding, and fatal
bleeding, using a subset of patients with atrial fibrillation (n=40 404). We
divided patients into quintiles based on their level of control for TTR, log INR
variability, and WCM. We calculated the hazard ratios for ischemic stroke, major
bleeding, and fatal bleeding stratified by these quintiles. WCM hazard ratios for
stroke and fatal bleeding showed the largest difference between excellent control
and poorest control quintile compared with TTR and log INR variability, but not
for major bleeding. In addition, we compared site rankings obtained using each of
our 3 performance measures. Kappa scores for identifying outlier and nonoutlier
clinics between WCM and its components were moderate (kappa=0.56 for TTR and
kappa=0.62 for log INR variability) but was weak between TTR and log INR
variability (kappa=0.13). CONCLUSIONS: WCM produces the largest range of risk for
warfarin complications, widening the floor ceiling effects that limit the use of
TTR and INR variability as separate measures. Anticoagulation clinics ranking
changed considerably according to the anticoagulation measure that was selected.
PMID- 26420821
TI - Relaxation therapy and anxiety, self-esteem, and emotional regulation among
adults with intellectual disabilities: A randomized controlled trial.
AB - This pilot study is a randomized controlled trial on the effects of relaxation on
anxiety, self-esteem, and emotional regulation in adults with intellectual
disabilities (ID) working in a center of supported employment in France. We
studied 30 adults with mild or moderate ID who were split at random into a
relaxation group (RG, 15 subjects), who completed 10 sessions of relaxation
therapy, and a control group (CG, 15 subjects), who were on a waiting list. The
method used is the pretest and posttest. Variables were assessed by the State
Trait Anxiety Inventory form Y scale, the Rosenberg Self-Esteem scale, and the
Emotion Regulation Questionnaire. We found that in the RG, relaxation
significantly reduced state anxiety, t(14, 15) = 17.8***, d = -0.72, and improved
self-esteem, t(14, 15) = -7.7***, d = 1.03, and cognitive reappraisal, t(14, 15)
= -6.3***, d = 1.3, while the CG showed no change for these variables. We
conclude that relaxation seems to be an interesting therapeutic option for
reducing anxiety in people with ID in a supported employment setting.
PMID- 26420822
TI - AML treatment in older adults.
PMID- 26420823
TI - Sonic Hedgehog in SCLC.
PMID- 26420824
TI - Use of the Delphi process in paediatric cataract management.
AB - PURPOSE: To identify areas of consensus and disagreement in the management of
paediatric cataract using a modified Delphi approach among individuals recognised
for publishing in this field. DESIGN: A modified Delphi method. PARTICIPANTS:
International paediatric cataract experts with a publishing record in paediatric
cataract management. METHODS: The process consisted of three rounds of anonymous
electronic questionnaires followed by a face-to-face meeting, followed by a
fourth anonymous electronic questionnaire. The executive committee created
questions to be used for the electronic questionnaires. Questions were designed
to have unit-based, multiple choice or true-false answers. The questionnaire
included issues related to the preoperative, intraoperative and postoperative
management of paediatric cataract. MAIN OUTCOME MEASURE: Consensus based on 85%
of panellists being in agreement for electronic questionnaires or 80% for the
face-to-face meeting, and near consensus based on 70%. RESULTS: Sixteen of 22
invited paediatric cataract surgeons agreed to participate. We arrived at
consensus or near consensus for 85/108 (78.7%) questions and non-consensus for
the remaining 23 (21.3%) questions. CONCLUSIONS: Those questions where consensus
was not reached highlight areas of either poor evidence or contradicting
evidence, and may help investigators identify possible research questions.
PMID- 26420825
TI - Interobserver agreement using Goldmann applanation tonometry and dynamic contour
tonometry: comparing ophthalmologists, nurses and technicians.
AB - PURPOSE: To compare agreement between ophthalmologists and non-ophthalmologists
(nurses and ophthalmic technicians) when measuring the intraocular pressure (IOP)
using Goldmann applanation tonometry (GAT) and Pascal dynamic contour tonometry
(DCT). METHODS: Patients attending for their routine glaucoma outpatient
appointment were invited to participate. IOP was measured in one eye by either
two ophthalmologists (observer group 1), two non-ophthalmologists (observer group
2) or one ophthalmologist and one non-ophthalmologist (observer group 3). All
were experienced in using GAT and some experienced in using the DCT. The order of
tonometer and staff was randomised. Agreement was calculated by Bland-Altman
analysis, with the mean difference and 95% limits of agreement (LoA) of
measurements calculated for each observer group. RESULTS: One hundred eyes were
measured within each observer group. The mean difference (95% LoA) in IOP
measurements were GAT: group 1=-0.20 (4.9) mm Hg, group 2=0.6 (5.4) mm Hg and
group 3=0.0 (3.7) mm Hg; DCT: group 1=0.8 (7.7) mm Hg, group 2=0.3 (4.2) and
group 3=0.0 (5.2) mm Hg. The DCT consistently over-read the GAT for all observer
groups. DISCUSSION/CONCLUSIONS: Ophthalmologists show good levels of agreement
with each other when using GAT, while technicians/nursing staff show better
agreement when using the DCT. The DCT may be a better tonometer to use if
permanently delegating IOP measurements to non-ophthalmologists, but measurements
cannot be interchanged with the GAT.
PMID- 26420826
TI - Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated
proteins.
AB - Splicing factor 1 (SF1) recognizes the branch point sequence (BPS) at the 3'
splice site during the formation of early complex E, thereby pre-bulging the BPS
adenosine, thought to facilitate subsequent base-pairing of the U2 snRNA with the
BPS. The 65-kDa subunit of U2 snRNP auxiliary factor (U2AF65) interacts with SF1
and was shown to recruit the U2 snRNP to the spliceosome. Co-immunoprecipitation
experiments of SF1-interacting proteins from HeLa cell extracts shown here are
consistent with the presence of SF1 in early splicing complexes. Surprisingly
almost all U2 snRNP proteins were found associated with SF1. Yeast two-hybrid
screens identified two SURP domain-containing U2 snRNP proteins as partners of
SF1. A short, evolutionarily conserved region of SF1 interacts with the SURP
domains, stressing their role in protein-protein interactions. A reduction of A
complex formation in SF1-depleted extracts could be rescued with recombinant SF1
containing the SURP-interaction domain, but only partial rescue was observed with
SF1 lacking this sequence. Thus, SF1 can initially recruit the U2 snRNP to the
spliceosome during E complex formation, whereas U2AF65 may stabilize the
association of the U2 snRNP with the spliceosome at later times. In addition,
these findings may have implications for alternative splicing decisions.
PMID- 26420827
TI - Direct-Coupling Analysis of nucleotide coevolution facilitates RNA secondary and
tertiary structure prediction.
AB - Despite the biological importance of non-coding RNA, their structural
characterization remains challenging. Making use of the rapidly growing sequence
databases, we analyze nucleotide coevolution across homologous sequences via
Direct-Coupling Analysis to detect nucleotide-nucleotide contacts. For a
representative set of riboswitches, we show that the results of Direct-Coupling
Analysis in combination with a generalized Nussinov algorithm systematically
improve the results of RNA secondary structure prediction beyond traditional
covariance approaches based on mutual information. Even more importantly, we show
that the results of Direct-Coupling Analysis are enriched in tertiary structure
contacts. By integrating these predictions into molecular modeling tools,
systematically improved tertiary structure predictions can be obtained, as
compared to using secondary structure information alone.
PMID- 26420829
TI - GeoPCA: a new tool for multivariate analysis of dihedral angles based on
principal component geodesics.
PMID- 26420828
TI - DNA double-strand breaks with 5' adducts are efficiently channeled to the DNA2
mediated resection pathway.
AB - DNA double-strand breaks (DSBs) with 5' adducts are frequently formed from many
nucleic acid processing enzymes, in particular DNA topoisomerase 2 (TOP2). The
key intermediate of TOP2 catalysis is the covalent complex (TOP2cc), consisting
of two TOP2 subunits covalently linked to the 5' ends of the nicked DNA. In
cells, TOP2ccs can be trapped by cancer drugs such as etoposide and then
converted into DNA double-strand breaks (DSBs) that carry adducts at the 5' end.
The repair of such DSBs is critical to the survival of cells, but the underlying
mechanism is still not well understood. We found that etoposide-induced DSBs are
efficiently resected into 3' single-stranded DNA in cells and the major nuclease
for resection is the DNA2 protein. DNA substrates carrying model 5' adducts were
efficiently resected in Xenopus egg extracts and immunodepletion of Xenopus DNA2
also strongly inhibited resection. These results suggest that DNA2-mediated
resection is a major mechanism for the repair of DSBs with 5' adducts.
PMID- 26420830
TI - DnaC traps DnaB as an open ring and remodels the domain that binds primase.
AB - Helicase loading at a DNA replication origin often requires the dynamic
interactions between the DNA helicase and an accessory protein. In E. coli, the
DNA helicase is DnaB and DnaC is its loading partner. We used the method of
hydrogen/deuterium exchange mass spectrometry to address the importance of DnaB
DnaC complex formation as a prerequisite for helicase loading. Our results show
that the DnaB ring opens and closes, and that specific amino acids near the N
terminus of DnaC interact with a site in DnaB's C-terminal domain to trap it as
an open ring. This event correlates with conformational changes of the RecA fold
of DnaB that is involved in nucleotide binding, and of the AAA+ domain of DnaC.
DnaC also causes an alteration of the helical hairpins in the N-terminal domain
of DnaB, presumably occluding this region from interacting with primase. Hence,
DnaC controls the access of DnaB by primase.
PMID- 26420831
TI - ATM and KAT5 safeguard replicating chromatin against formaldehyde damage.
AB - Many carcinogens damage both DNA and protein constituents of chromatin, and it is
unclear how cells respond to this compound injury. We examined activation of the
main DNA damage-responsive kinase ATM and formation of DNA double-strand breaks
(DSB) by formaldehyde (FA) that forms histone adducts and replication-blocking
DNA-protein crosslinks (DPC). We found that low FA doses caused a strong and
rapid activation of ATM signaling in human cells, which was ATR-independent and
restricted to S-phase. High FA doses inactivated ATM via its covalent
dimerization and formation of larger crosslinks. FA-induced ATM signaling showed
higher CHK2 phosphorylation but much lower phospho-KAP1 relative to DSB inducers.
Replication blockage by DPC did not produce damaged forks or detectable amounts
of DSB during the main wave of ATM activation, which did not require MRE11.
Chromatin-monitoring KAT5 (Tip60) acetyltransferase was responsible for
acetylation and activation of ATM by FA. KAT5 and ATM were equally important for
triggering of intra-S-phase checkpoint and ATM signaling promoted recovery of
normal human cells after low-dose FA. Our results revealed a major role of the
KAT5-ATM axis in protection of replicating chromatin against damage by the
endogenous carcinogen FA.
PMID- 26420832
TI - The players may change but the game remains: network analyses of ruminal
microbiomes suggest taxonomic differences mask functional similarity.
AB - By mapping translated metagenomic reads to a microbial metabolic network, we show
that ruminal ecosystems that are rather dissimilar in their taxonomy can be
considerably more similar at the metabolic network level. Using a new network bi
partition approach for linking the microbial network to a bovine metabolic
network, we observe that these ruminal metabolic networks exhibit properties
consistent with distinct metabolic communities producing similar outputs from
common inputs. For instance, the closer in network space that a microbial
reaction is to a reaction found in the host, the lower will be the variability of
its enzyme copy number across hosts. Similarly, these microbial enzymes that are
nearby to host nodes are also higher in copy number than are more distant
enzymes. Collectively, these results demonstrate a widely expected pattern that,
to our knowledge, has not been explicitly demonstrated in microbial communities:
namely that there can exist different community metabolic networks that have the
same metabolic inputs and outputs but differ in their internal structure.
PMID- 26420833
TI - Reduced cohesin destabilizes high-level gene amplification by disrupting pre
replication complex bindings in human cancers with chromosomal instability.
AB - Gene amplification is a hallmark of cancer with chromosomal instability although
the underlying mechanism by which altered copy numbers are maintained is largely
unclear. Cohesin, involved in sister chromatid cohesion, DNA repair, cell cycle
progression and transcriptional regulation of key developmental genes, is
frequently overexpressed in human cancer. Here we show that cohesin-dependent
change in DNA replication controls the copy numbers of amplified genes in cancer
cells with chromosomal instability. We found that the down-regulation of elevated
cohesin leads to copy number-associated gene expression changes without
disturbing chromosomal segregation. Highly amplified genes form typical long
range chromatin interactions, which are stabilized by enriched cohesin. The
spatial proximities among cohesin binding sites within amplified genes are
decreased by RAD21-knockdown, resulting in the rapid decline of amplified gene
expression. After several passages, cohesin depletion inhibits DNA replication
initiation by reducing the recruitment of pre-replication complexes such as
minichromosome maintenance subunits 7 (MCM7), DNA polymerase alpha, and CDC45 at
replication origins near the amplified regions, and as a result, decreases the
DNA copy numbers of highly amplified genes. Collectively, our data demonstrate
that cohesin-mediated chromatin organization and DNA replication are important
for stabilizing gene amplification in cancer cells with chromosomal instability.
PMID- 26420835
TI - Ultra-fast local-haplotype variant calling using paired-end DNA-sequencing data
reveals somatic mosaicism in tumor and normal blood samples.
AB - Somatic mosaicism refers to the existence of somatic mutations in a fraction of
somatic cells in a single biological sample. Its importance has mainly been
discussed in theory although experimental work has started to emerge linking
somatic mosaicism to disease diagnosis. Through novel statistical modeling of
paired-end DNA-sequencing data using blood-derived DNA from healthy donors as
well as DNA from tumor samples, we present an ultra-fast computational pipeline,
LocHap that searches for multiple single nucleotide variants (SNVs) that are
scaffolded by the same reads. We refer to scaffolded SNVs as local haplotypes
(LH). When an LH exhibits more than two genotypes, we call it a local haplotype
variant (LHV). The presence of LHVs is considered evidence of somatic mosaicism
because a genetically homogeneous cell population will not harbor LHVs. Applying
LocHap to whole-genome and whole-exome sequence data in DNA from normal blood and
tumor samples, we find wide-spread LHVs across the genome. Importantly, we find
more LHVs in tumor samples than in normal samples, and more in older adults than
in younger ones. We confirm the existence of LHVs and somatic mosaicism by
validation studies in normal blood samples. LocHap is publicly available at
http://www.compgenome.org/lochap.
PMID- 26420834
TI - ANISEED 2015: a digital framework for the comparative developmental biology of
ascidians.
AB - Ascidians belong to the tunicates, the sister group of vertebrates and are
recognized model organisms in the field of embryonic development, regeneration
and stem cells. ANISEED is the main information system in the field of ascidian
developmental biology. This article reports the development of the system since
its initial publication in 2010. Over the past five years, we refactored the
system from an initial custom schema to an extended version of the Chado schema
and redesigned all user and back end interfaces. This new architecture was used
to improve and enrich the description of Ciona intestinalis embryonic
development, based on an improved genome assembly and gene model set, refined
functional gene annotation, and anatomical ontologies, and a new collection of
full ORF cDNAs. The genomes of nine ascidian species have been sequenced since
the release of the C. intestinalis genome. In ANISEED 2015, all nine new ascidian
species can be explored via dedicated genome browsers, and searched by Blast. In
addition, ANISEED provides full functional gene annotation, anatomical ontologies
and some gene expression data for the six species with highest quality genomes.
ANISEED is publicly available at: http://www.aniseed.cnrs.fr.
PMID- 26420839
TI - Molecular and biochemical alterations in tubular epithelial cells of patients
with isolated methylmalonic aciduria.
AB - Methylmalonic acidurias (MMAurias) are a group of inherited disorders in the
catabolism of branched-chain amino acids, odd-chain fatty acids and cholesterol
caused by complete or partial deficiency of methylmalonyl-CoA mutase (mut(0) and
mut(-) subtype respectively) and by defects in the metabolism of its cofactor 5'
deoxyadenosylcobalamin (cblA, cblB or cblD variant 2 type). A long-term
complication found in patients with mut(0) and cblB variant is chronic
tubulointerstitial nephritis. The underlying pathomechanism has remained unknown.
We established an in vitro model of tubular epithelial cells from patient urine
(hTEC; 9 controls, 5 mut(0), 1 cblB). In all human tubular epithelial cell (hTEC)
lines we found specific tubular markers (AQP1, UMOD, AQP2). Patient cells showed
disturbance of energy metabolism in glycolysis, mitochondrial respiratory chain
and Krebs cycle in concert with increased reactive oxygen species (ROS)
formation. Electron micrographs indicated increased autophagosome production and
endoplasmic reticulum stress, which was supported by positive acridine orange
staining and elevated levels of LC3 II, P62 and pIRE1. Screening mTOR signaling
revealed a release of inhibition of autophagy. Patient hTEC produced and secreted
elevated amounts of the pro-inflammatory cytokine IL8, which was highly
correlated with the acridine orange staining. Summarizing, hTEC of MMAuria
patients are characterized by disturbed energy metabolism and ROS production that
lead to increased autophagy and IL8 secretion.
PMID- 26420838
TI - Neuronopathic Gaucher disease: dysregulated mRNAs and miRNAs in brain
pathogenesis and effects of pharmacologic chaperone treatment in a mouse model.
AB - Defective lysosomal acid beta-glucosidase (GCase) in Gaucher disease causes
accumulation of glucosylceramide (GC) and glucosylsphingosine (GS) that distress
cellular functions. To study novel pathological mechanisms in neuronopathic
Gaucher disease (nGD), a mouse model (4L;C*), an analogue to subacute human nGD,
was investigated for global profiles of differentially expressed brain mRNAs
(DEGs) and miRNAs (DEmiRs). 4L;C* mice displayed accumulation of GC and GS,
activated microglial cells, reduced number of neurons and aberrant mitochondrial
function in the brain followed by deterioration in motor function. DEGs and
DEmiRs were characterized from sequencing of mRNA and miRNA from cerebral cortex,
brain stem, midbrain and cerebellum of 4L;C* mice. Gene ontology enrichment and
pathway analysis showed preferential mitochondrial dysfunction in midbrain and
uniform inflammatory response and identified novel pathways, axonal guidance
signaling, synaptic transmission, eIF2 and mammalian target of rapamycin (mTOR)
signaling potentially involved in nGD. Similar analyses were performed with mice
treated with isofagomine (IFG), a pharmacologic chaperone for GCase. IFG
treatment did not alter the GS and GC accumulation significantly but attenuated
the progression of the disease and altered numerous DEmiRs and target DEGs to
their respective normal levels in inflammation, mitochondrial function and axonal
guidance pathways, suggesting its regulation on miRNA and the associated mRNA
that underlie the neurodegeneration in nGD. These analyses demonstrate that the
neurodegenerative phenotype in 4L;C* mice was associated with dysregulation of
brain mRNAs and miRNAs in axonal guidance, synaptic plasticity, mitochondria
function, eIF2 and mTOR signaling and inflammation and provides new insights for
the nGD pathological mechanism.
PMID- 26420840
TI - A neural crest origin for cohesinopathy heart defects.
AB - Mutations in subunits or regulators of cohesin cause a spectrum of disorders in
humans known as the 'cohesinopathies'. Cohesinopathies, including the best known
example Cornelia de Lange syndrome (CdLS), are characterized by broad spectrum,
multifactorial developmental anomalies. Heart defects occur at high frequency and
can reach up to 30% in CdLS. The mechanisms by which heart defects occur are
enigmatic, but assumed to be developmental in origin. In this study, we depleted
cohesin subunit Rad21 by 70-80% in a zebrafish cohesinopathy model. The hearts of
Rad21-depleted animals were smaller, often failed to loop, and functioned less
efficiently than size-matched controls. Functional deficiency was accompanied by
valve defects and reduced ejection fraction. Interestingly, neural crest cells
failed to populate the heart and instead exhibited a wandering behavior.
Consequently, these cells also failed to condense correctly into pharyngeal
arches. Transcriptome analysis revealed that Wnt pathway, chemokine and cadherin
genes are dysregulated at the time of cardiac neural crest development. Our
results give insight into the etiology of heart defects in the cohesinopathies,
and raise the possibility that mild mutations in cohesin genes may be causative
of a fraction of congenital heart disease in human populations.
PMID- 26420841
TI - Mutsbeta generates both expansions and contractions in a mouse model of the
Fragile X-associated disorders.
AB - Fragile X-associated disorders are Repeat Expansion Diseases that result from
expansion of a CGG/CCG-repeat in the FMR1 gene. Contractions of the repeat tract
also occur, albeit at lower frequency. However, these contractions can
potentially modulate disease symptoms or generate an allele with repeat numbers
in the normal range. Little is known about the expansion mechanism and even less
about contractions. We have previously demonstrated that the mismatch repair
(MMR) protein MSH2 is required for expansions in a mouse model of these
disorders. Here, we show that MSH3, the MSH2-binding partner in the MutSbeta
complex, is required for 98% of germ line expansions and all somatic expansions
in this model. In addition, we provide evidence for two different contraction
mechanisms that operate in the mouse model, a MutSbeta-independent one that
generates small contractions and a MutSbeta-dependent one that generates larger
ones. We also show that MutSbeta complexes formed with the repeats have altered
kinetics of ATP hydrolysis relative to complexes with bona fide MMR substrates
and that MutSbeta increases the stability of the CCG-hairpins at physiological
temperatures. These data may have important implications for our understanding of
the mechanism(s) of repeat instability and for the role of MMR proteins in this
process.
PMID- 26420844
TI - Allee effects in tritrophic food chains: some insights in pest biological
control.
AB - Release of natural enemies to control pest populations is a common strategy in
biological control. However, its effectiveness is supposed to be impaired, among
other factors, by Allee effects in the biological control agent and by the fact
that introduced pest natural enemies interact with some native species of the
ecosystem. In this work, we devise a tritrophic food chain model where the
assumptions previously raised are proved correct when a hyperpredator attacks the
introduced pest natural enemy by a functional response type 2 or 3. Moreover,
success of pest control is shown to be related to the release of large amounts
(i.e., inundative releases) of natural enemies.
PMID- 26420842
TI - Improved dual AAV vectors with reduced expression of truncated proteins are safe
and effective in the retina of a mouse model of Stargardt disease.
AB - Stargardt disease (STGD1) due to mutations in the large ABCA4 gene is the most
common inherited macular degeneration in humans. We have shown that dual adeno
associated viral (AAV) vectors effectively transfer ABCA4 to the retina of Abca4
/- mice. However, they express both lower levels of transgene compared with a
single AAV and truncated proteins. To increase productive dual AAV
concatemerization, which would overcome these limitations, we have explored the
use of either various regions of homology or heterologous inverted terminal
repeats (ITR). In addition, we tested the ability of various degradation signals
to decrease the expression of truncated proteins. We found the highest levels of
transgene expression using regions of homology based on either alkaline
phosphatase or the F1 phage (AK). The use of heterologous ITR does not decrease
the levels of truncated proteins relative to full-length ABCA4 and impairs AAV
vector production. Conversely, the inclusion of the CL1 degradation signal
results in the selective degradation of truncated proteins from the 5'-half
without affecting full-length protein production. Therefore, we developed dual
AAV hybrid ABCA4 vectors including homologous ITR2, the photoreceptor-specific G
protein-coupled receptor kinase 1 promoter, the AK region of homology and the CL1
degradation signal. We show that upon subretinal administration these vectors are
both safe in pigs and effective in Abca4-/- mice. Our data support the use of
improved dual AAV vectors for gene therapy of STGD1.
PMID- 26420843
TI - A study of whirlin isoforms in the mouse vestibular system suggests potential
vestibular dysfunction in DFNB31-deficient patients.
AB - The DFNB31 gene plays an indispensable role in the cochlea and retina. Mutations
in this gene disrupt its various isoforms and lead to non-syndromic deafness,
blindness and deaf-blindness. However, the known expression of Dfnb31, the mouse
ortholog of DFNB31, in vestibular organs and the potential vestibular-deficient
phenotype observed in one Dfnb31 mutant mouse (Dfnb31(wi/wi)) suggest that DFNB31
may also be important for vestibular function. In this study, we find that full
length (FL-) and C-terminal (C-) whirlin isoforms are expressed in the vestibular
organs, where their stereociliary localizations are similar to those of
developing cochlear inner hair cells. No whirlin is detected in Dfnb31(wi/wi)
vestibular organs, while only C-whirlin is expressed in Dfnb31(neo/neo)
vestibular organs. Both FL- and C-whirlin isoforms are required for normal
vestibular stereociliary growth, although they may play slightly different roles
in the central and peripheral zones of the crista ampullaris. Vestibular sensory
evoked potentials demonstrate severe to profound vestibular deficits in
Dfnb31(neo/neo) and Dfnb31(wi/wi) mice. Swimming and rotarod tests demonstrate
that the two Dfnb31 mutants have balance problems, with Dfnb31(wi/wi) mice being
more affected than Dfnb31(neo/neo) mice. Because Dfnb31(wi/wi) and
Dfnb31(neo/neo) mice faithfully recapitulate hearing and vision symptoms in
patients, our findings of vestibular dysfunction in these Dfnb31 mutants raise
the question of whether DFNB31-deficient patients may acquire vestibular as well
as hearing and vision loss.
PMID- 26420845
TI - Utilizing community and voluntary sector partnerships to survey and compare the
health outcomes of hard-to- reach groups to the wider community-the EURO- URHIS 2
Hard-to-Reach Project.
AB - Background: This article describes the Hard-to-Reach (HtR) Project that was
developed to capture health and lifestyle data from groups who are HtR by postal
surveys within the larger EURO-URHIS 2 project. By collaborating with partner
organizations, data were collected using standard survey tools, allowing for
comparison with the wider population. Following a scoping exercise to determine
which groups were HtR in Greater Manchester, black and minority ethnic (BME)
groups and students were selected. BME groups were surveyed through partnership
with Community and Voluntary Sector Organizations (CVSOs). Language barriers were
addressed through the recruitment of volunteer interpreters. Students were
surveyed by accessing university premises. Fifteen survey visits took place at
nine CVSOs and five visits to University facilities. In total, 144 eligible
surveys were collected. There were significant differences for both HtR groups,
compared with Greater Manchester and the EURO-URHIS 2 mean. Both HtR groups had
worse outcomes than both Greater Manchester and EURO-URHIS 2 for psychological
problems. In addition, students had worse outcomes for passive smoking, binge
drinking, use of cannabis, lack of access to green spaces, less sense of
belonging and social cohesion and damp or mildewed homes, and better outcomes for
self-perceived health and overweight and obesity. BME had in addition worse
outcomes than both Greater Manchester and EURO-URHIS 2 for long-standing
restrictive illness. Despite the limitations of this study, the development of
this methodology allowed for the collection of comparable data, showing up
statistically significant differences between the HtR populations and the wider
population which merits further investigation.
PMID- 26420846
TI - Suicide mortality at time of armed conflict in Ukraine.
AB - The purpose of this review is to explore the dynamics of suicide mortality rates
in Ukraine during an ongoing armed conflict between 2014 and 2015. Suicide
mortality data were obtained by reviewing annual analytical releases from the
State Service for Emergent Situations of Ukraine and annual release of Russian
Federal Service of State Statistics. Suicide mortality in mainland Ukraine and in
the Crimea region demonstrated a mild decrease, whereas suicide mortality in the
regions directly involved in the armed conflict demonstrated a prominent
decrease. The results of this review support Durkheim theory. The limitation of
this review includes general concern about quality of data at time of armed
conflict in the country.
PMID- 26420847
TI - A retrospective evaluation of the intrauterine device in a patient population in
Buenos Aires, Argentina.
AB - BACKGROUND: The intrauterine device (IUD) is a long-acting reversible
contraceptive method that is safe for a wide range of women, including
adolescents and nulliparous women. Globally, it is often underutilised due to
misperceptions among patients. Examination of characteristics associated with IUD
discontinuation including adverse effects and IUD expulsion can inform provider
practices to improve contraception success and patient satisfaction with this
method. We studied IUD performance at a public family planning clinic in Buenos
Aires, Argentina, serving a predominantly immigrant, low-income population.
METHODS: We conducted a retrospective evaluation of 1047 IUD insertions between
2002 and 2007 with 5 years of follow-up data. We performed bivariate and survival
analysis to examine characteristics associated with IUD discontinuation: adverse
outcomes including pain, bleeding, and IUD expulsion, and time to removal.
FINDINGS: Of 1047 patients, only 188 (18%) had their IUD removed within 5 years.
The main causes of IUD discontinuation were involuntary (38%) reasons such as an
IUD expulsion and personal choice (34%) such as desiring pregnancy. CONCLUSIONS:
Findings suggest overall good long-term performance with IUD insertion, with
minimal complaints or adverse outcomes. These findings may help to support
providers serving similar populations in promoting this method.
PMID- 26420848
TI - Prioritization in Somali health system strengthening: a qualitative study.
AB - BACKGROUND: After years of decline and disintegration, the Somalia Federal
Government alongside international and domestic partners is beginning the process
of rebuilding its national health system. In this study, we aim to shed light on
the current approaches to health system strengthening, as viewed by stakeholders
closely involved in its development. METHODS: Key informant interviews were
undertaken with health and development professionals working within all three
administrative regions of Somalia, as well as with Somali ministry of health
officials, global health and policy specialists with interests in health system
reconstruction in fragile states. A review of published and grey literature on
Somalia, health systems, fragile and conflict-affected countries using PubMed and
Reliefweb was also conducted. Technical documents designed for Somali health
system building by external development partners were also reviewed. RESULTS: Key
priorities identified by participants were, strengthening of local governance and
management capacity, scaling-up efforts to structure a robust health financing
mechanism, engagement with the burgeoning and dynamic private sector, as well as
investing in the appropriate human resources for health. CONCLUSIONS: The study
found that there was widespread agreement among participants that health system
strengthening through a coordinated system would improve long-term capacity in
Somalia's health sector. Future research should focus on the evaluation of the
modalities by which health system strengthening interventions are implemented, on
neglected topics such as mental health within the Somali health system, as well
as on population-level barriers to accessing health systems.
PMID- 26420849
TI - Multitargeting of selected prostanoid receptors provides agents with enhanced
anti-inflammatory activity in macrophages.
AB - A polypharmacologic approach to prostanoid based anti-inflammatory therapeutics
was undertaken in order to exploit both the anti- and proinflammatory properties
attributed to the various prostanoid receptors. Multitargeting of selected
prostanoid receptors yielded a prototype compound, compound 1 (AGN 211377), that
antagonizes prostaglandin D2 receptors (DPs) DP1 (49) and DP2 (558),
prostaglandin E2 receptors (EPs) EP1 (266) and EP4 (117), prostaglandin F2alpha
receptor (FP) (61), and thromboxane A2 receptor (TP) (11) while sparing EP2, EP3,
and prostaglandin I2 receptors (IPs); Kb values (in nanomoles) are given in
parentheses. Compound 1 evoked a pronounced inhibition of cytokine/chemokine
secretion from lipopolysaccharide or TNF-alpha stimulated primary human
macrophages. These cytokine/chemokines included cluster of designation 40
receptor (CD40), epithelial-derived neutrophil-activating protein 78 (ENA-78),
granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony
stimulating factor (GM-CSF), IL-8, IL-18, monocyte chemotactic protein-1 (CCL2)
(MCP-1), tissue plasminogen activator inhibitor (PAI-1), and regulated on
activation, normal T cell expressed and secreted (RANTES). In contrast, the
inhibitory effects of most antagonists selective for a single receptor were
modest or absent, and selective EP2 receptor blockade increased cytokine release
in some instances. Compound 1 also showed clear superiority to the cyclooxygenase
inhibitors diclofenac and rofecoxib. These findings reveal that blockade of
multiple prostanoid receptors, with absent antagonism of EP2 and IP, may provide
more effective anti-inflammatory activity than global suppression of prostanoid
synthesis or highly selective prostanoid receptor blockade. These investigations
demonstrate the first working example of prostanoid receptor polypharmacology for
potentially safer and more effective anti-inflammatory therapeutics by blocking
multiple proinflammatory receptors while sparing those with anti-inflammatory
activity.
PMID- 26420851
TI - Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii
and Bifidobacterium adolescentis.
AB - Cross-feeding is an important metabolic interaction mechanism of bacterial groups
inhabiting the human colon and includes features such as the utilization of
acetate by butyrate-producing bacteria as may occur between Bifidobacterium and
Faecalibacterium genera. In this study, we assessed the utilization of different
carbon sources (glucose, starch, inulin and fructooligosaccharides) by strains of
both genera and selected the best suited combinations for evidencing this cross
feeding phenomenon. Co-cultures of Bifidobacterium adolescentis L2-32 with
Faecalibacterium prausnitzii S3/L3 with fructooligosaccharides as carbon source,
as well as with F. prausnitzii A2-165 in starch, were carried out and the
production of short-chain fatty acids was determined. In both co-cultures,
acetate levels decreased between 8 and 24 h of incubation and were lower than in
the corresponding B. adolescentis monocultures. In contrast, butyrate
concentrations were higher in co-cultures as compared to the respective F.
prausnitzii monocultures, indicating enhanced formation of butyrate by F.
prausnitzii in the presence of the bifidobacteria. Variations in the levels of
acetate and butyrate were more pronounced in the co-culture with
fructooligosaccharides than with starch. Our results provide a clear
demonstration of cross-feeding between B. adolescentis and F. prausnitzii.
PMID- 26420852
TI - Inhibiting NAD+-dependent DNA ligase activity with 2-(cyclopentyloxy)-5'
deoxyadenosine (CPOdA) offers a new tool for DNA replication and repair studies
in the model archaeon Haloferax volcanii.
AB - DNA ligases play an essential role in many aspects of DNA metabolism in all three
domains of life. The haloarchaeal organism Haloferax volcanii encodes both ATP-
and NAD(+)-dependent DNA ligase enzymes designated LigA and LigN, respectively.
Neither LigA nor LigN alone is required for cell viability but they share an
essential function, most likely the ligation of Okazaki fragments during
chromosome replication. Here we show that 2-(cyclopentyloxy)-5'-deoxyadenosine
(referred to as CPOdA), originally developed as a inhibitor of bacterial NAD(+)
dependent DNA ligases, is a potent inhibitor of the growth of Hfx. volcanii cells
expressing LigN alone, causing chromosome fragmentation and cell death, while
cells expressing LigA are unaffected. Growth inhibition occurs at significantly
lower CPOdA concentrations (MIC <= 50 ng ml(-1)) than those required for
inhibition of bacterial growth (>=2 MUg ml(-1)). CPOdA has the potential to
become a vital tool in DNA replication and repair studies in this important model
organism.
PMID- 26420853
TI - Spontaneous and on point: Do spontaneous mutations used for laboratory
experiments cause pleiotropic effects that might confound bacterial infection and
evolution assays?
AB - Many selectable phenotypes in microbial systems, including antibiotic resistance,
can be conferred by single point mutations. This is frequently exploited in
research, where the selection and use of microbial mutants that are spontaneously
resistant to antibiotics like rifampicin and streptomycin facilitate the recovery
and/or quantification of a target microbe. Such mutations are commonly employed
as genetic markers for in vitro and in vivo experiments, often with little
consideration as to the ultimate system-level impact of these single nucleotide
mutations on the physiology of the microbe. There is substantial literature on
the pleiotropic effects of point mutations conferring antibiotic resistance; yet,
it is unclear whether this work is considered by the research communities outside
of the discipline. This review examines some of the known pleiotropic effects of
point mutations that provide selectable resistance markers, and how these
mutations may impact general physiology and growth in host and non-host
environments.
PMID- 26420855
TI - Extent and Location of Tumor-Infiltrating Lymphocytes in Microsatellite-Stable
Colon Cancer Predict Outcome to Adjuvant Active Specific Immunotherapy.
AB - PURPOSE: To determine the prognostic and predictive value of tumor-infiltrating
lymphocytes (TIL) in colon cancer in a cohort of patients who previously took
part in a trial on adjuvant active specific immunotherapy (ASI). EXPERIMENTAL
DESIGN: We determined the number and location of CD3 and CD8 positive T cells in
archival tumor samples of 106 colon cancers. We correlated stromal and epithelial
TIL numbers with tumor stage and treatment and determined the effects on disease
specific survival (DSS) and recurrence-free interval (RFI). RESULTS: On the basis
of the data presented, we concluded that (i) high numbers of stromal CD3 T cells
have positive prognostic value measured as DSS for patients with stage II
microsatellite-stable tumors and (ii) high numbers of epithelial CD8-positive T
cells have positive prognostic value measured as RFI for the group of patients
with stage II microsatellite-stable tumors as well as for the whole group (so
stage II plus stage III together). Furthermore, we concluded that high numbers of
pre-existing stromal CD3-positive T cells are of positive predictive value in
adjuvant ASI treatment measured as DSS as well as RFI. CONCLUSIONS: ASI therapy
may contribute to an improved DSS and RFI in patients with microsatellite-stable
colon tumors harboring high numbers of pre-existing stromal CD3(+) TIL.
Validation in future clinical trials is awaited.
PMID- 26420854
TI - Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine
Enhances Local HPV-Specific CD8+ T-cell-Mediated Tumor Control in the Genital
Tract.
AB - PURPOSE: Two viral oncoproteins, E6 and E7, are expressed in all human
papillomavirus (HPV)-infected cells, from initial infection in the genital tract
to metastatic cervical cancer. Intramuscular vaccination of women with high-grade
cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine,
pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant
vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T-cell responses
that could traffic to the lesion and was associated with regression in some
patients (NCT00788164). EXPERIMENTAL DESIGN: Here, we examine whether alteration
of this vaccination regimen by administration of TA-HPV vaccination in the
cervicovaginal tract, rather than intramuscular (IM) delivery, can more
effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse
model of HPV16(+) cervical cancer (TC-1 luc). RESULTS: We found that pNGVL4a
sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA
HPV increased accumulation of total and E7-specific CD8(+) T cells in the
cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc
tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8(+) T
cells in the cervicovaginal tract generated through the cervicovaginal route of
vaccination expressed the alpha4beta7 integrin and CCR9, which are necessary for
the homing of the E7-specific CD8(+) T cells to the cervicovaginal tract.
Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent
local HPV-16 E7 antigen-specific CD8(+) T-cell immune responses regardless of
whether an HPV DNA vaccine priming vaccination was administered IM or within the
cervicovaginal tract. CONCLUSIONS: Our results support future clinical
translation using cervicovaginal TA-HPV vaccination.
PMID- 26420857
TI - Pan-HER Inhibitor Augments Radiation Response in Human Lung and Head and Neck
Cancer Models.
AB - PURPOSE: Aberrant regulation of the EGF receptor family (EGFR, HER2, HER3, HER4)
contributes to tumorigenesis and metastasis in epithelial cancers. Pan-HER
represents a novel molecular targeted therapeutic composed of a mixture of six
monoclonal antibodies against EGFR, HER2, and HER3. EXPERIMENTAL DESIGN: In the
current study, we examine the capacity of Pan-HER to augment radiation response
across a series of human lung and head and neck cancers, including EGFR inhibitor
resistant cell lines and xenografts. RESULTS: Pan-HER demonstrates superior
antiproliferative and radiosensitizing impact when compared with cetuximab. The
mechanisms underlying these effects appear to involve attenuation of DNA damage
repair, enhancement of programmed cell death, cell-cycle redistribution, and
induction of cellular senescence. Combined treatment of Pan-HER with single or
fractionated radiation in human tumor xenografts reveals a potent antitumor and
regrowth delay impact compared with Pan-HER or radiation treatment alone.
CONCLUSIONS: These data highlight the capacity of Pan-HER to augment radiation
response in lung and head and neck cancer models and support investigation of Pan
HER combined with radiation as a promising clinical therapeutic strategy.
PMID- 26420856
TI - Molecular Pathways: Targeting Diacylglycerol Kinase Alpha in Cancer.
AB - Lipid kinases have largely been neglected as targets in cancer, and an increasing
number of reports suggest diacylglycerol kinase alpha (DGKalpha) may be one with
promising therapeutic potential. DGKalpha is one of 10 DGK family members that
convert diacylglycerol (DAG) to phosphatidic acid (PA), and both DAG and PA are
critical lipid second messengers in the plasma membrane. A host of important
oncogenic proteins and pathways affect cancer cells in part through DGKalpha,
including the c-Met and VEGF receptors. Others partially mediate the effects of
DGKalpha inhibition in cancer, such as mTOR and HIF-1alpha. DGKalpha inhibition
can directly impair cancer cell viability, inhibits angiogenesis, and notably may
also boost T-cell activation and enhance cancer immunotherapies. Although two
structurally similar inhibitors of DGKalpha were established decades ago, they
have seen minimal in vivo usage, and it is unlikely that either of these older
DGKalpha inhibitors will have utility for cancer. An abandoned compound that also
inhibits serotonin receptors may have more translational potential as a DGKalpha
inhibitor, but more potent and specific DGKalpha inhibitors are sorely needed.
Other DGK family members may also provide therapeutic targets in cancer, but
require further investigation.
PMID- 26420858
TI - A Patient-Derived, Pan-Cancer EMT Signature Identifies Global Molecular
Alterations and Immune Target Enrichment Following Epithelial-to-Mesenchymal
Transition.
AB - PURPOSE: We previously demonstrated the association between epithelial-to
mesenchymal transition (EMT) and drug response in lung cancer using an EMT
signature derived in cancer cell lines. Given the contribution of tumor
microenvironments to EMT, we extended our investigation of EMT to patient tumors
from 11 cancer types to develop a pan-cancer EMT signature. EXPERIMENTAL DESIGN:
Using the pan-cancer EMT signature, we conducted an integrated, global analysis
of genomic and proteomic profiles associated with EMT across 1,934 tumors
including breast, lung, colon, ovarian, and bladder cancers. Differences in
outcome and in vitro drug response corresponding to expression of the pan-cancer
EMT signature were also investigated. RESULTS: Compared with the lung cancer EMT
signature, the patient-derived, pan-cancer EMT signature encompasses a set of
core EMT genes that correlate even more strongly with known EMT markers across
diverse tumor types and identifies differences in drug sensitivity and global
molecular alterations at the DNA, RNA, and protein levels. Among those changes
associated with EMT, pathway analysis revealed a strong correlation between EMT
and immune activation. Further supervised analysis demonstrated high expression
of immune checkpoints and other druggable immune targets, such as PD1, PD-L1,
CTLA4, OX40L, and PD-L2, in tumors with the most mesenchymal EMT scores. Elevated
PD-L1 protein expression in mesenchymal tumors was confirmed by IHC in an
independent lung cancer cohort. CONCLUSIONS: This new signature provides a novel,
patient-based, histology-independent tool for the investigation of EMT and offers
insights into potential novel therapeutic targets for mesenchymal tumors,
independent of cancer type, including immune checkpoints.
PMID- 26420860
TI - The Metabolic Regulator Histone Deacetylase 9 Contributes to Glucose Homeostasis
Abnormality Induced by Hepatitis C Virus Infection.
AB - Class IIa histone deacetylases (HDACs), such as HDAC4, HDAC5, and HDAC7, provide
critical mechanisms for regulating glucose homeostasis. Here we report that
HDAC9, another class IIa HDAC, regulates hepatic gluconeogenesis via
deacetylation of a Forkhead box O (FoxO) family transcription factor, FoxO1,
together with HDAC3. Specifically, HDAC9 expression can be strongly induced upon
hepatitis C virus (HCV) infection. HCV-induced HDAC9 upregulation enhances
gluconeogenesis by promoting the expression of gluconeogenic genes, including
phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, indicating a major
role for HDAC9 in the development of HCV-associated exaggerated gluconeogenic
responses. Moreover, HDAC9 expression levels and gluconeogenic activities were
elevated in livers from HCV-infected patients and persistent HCV-infected mice,
emphasizing the clinical relevance of these results. Our results suggest HDAC9 is
involved in glucose metabolism, HCV-induced abnormal glucose homeostasis, and
type 2 diabetes.
PMID- 26420861
TI - Protein Biomarkers for Insulin Resistance and Type 2 Diabetes Risk in Two Large
Community Cohorts.
AB - Insulin resistance (IR) is a precursor of type 2 diabetes (T2D), and improved
risk prediction and understanding of the pathogenesis are needed. We used a novel
high-throughput 92-protein assay to identify circulating biomarkers for HOMA of
IR in two cohorts of community residents without diabetes (n = 1,367) (mean age
73 +/- 3.6 years). Adjusted linear regression identified cathepsin D and
confirmed six proteins (leptin, renin, interleukin-1 receptor antagonist [IL
1ra], hepatocyte growth factor, fatty acid-binding protein 4, and tissue
plasminogen activator [t-PA]) as IR biomarkers. Mendelian randomization analysis
indicated a positive causal effect of IR on t-PA concentrations. Two biomarkers,
IL-1ra (hazard ratio [HR] 1.28, 95% CI 1.03-1.59) and t-PA (HR 1.30, 1.02-1.65)
were associated with incident T2D, and t-PA predicted 5-year transition to
hyperglycemia (odds ratio 1.30, 95% CI 1.02-1.65). Additional adjustment for
fasting glucose rendered both coefficients insignificant and revealed an
association between renin and T2D (HR 0.79, 0.62-0.99). LASSO regression
suggested a risk model including IL-1ra, t-PA, and the Framingham Offspring Study
T2D score, but prediction improvement was nonsignificant (difference in C-index
0.02, 95% CI -0.08 to 0.12) over the T2D score only. In conclusion, proteomic
blood profiling indicated cathepsin D as a new IR biomarker and suggested a
causal effect of IR on t-PA.
PMID- 26420862
TI - FGF1 Mediates Overnutrition-Induced Compensatory beta-Cell Differentiation.
AB - Increased insulin demand resulting from insulin resistance and/or overnutrition
induces a compensatory increase in beta-cell mass. The physiological factors
responsible for the compensation have not been fully characterized. In zebrafish,
overnutrition rapidly induces compensatory beta-cell differentiation through
triggering the release of a paracrine signal from persistently activated beta
cells. We identified Fgf1 signaling as a key component of the overnutrition
induced beta-cell differentiation signal in a small molecule screen. Fgf1 was
confirmed as the overnutrition-induced beta-cell differentiation signal, as
inactivation of fgf1 abolished the compensatory beta-cell differentiation.
Furthermore, expression of human FGF1 solely in beta-cells in fgf1(-/-) animals
rescued the compensatory response, indicating that beta-cells can be the source
of FGF1. Additionally, constitutive secretion of FGF1 with an exogenous signal
peptide increased beta-cell number in the absence of overnutrition. These results
demonstrate that fgf1 is necessary and FGF1 expression in beta-cells is
sufficient for the compensatory beta-cell differentiation. We further show that
FGF1 is secreted during prolonged activation of cultured mammalian beta-cells and
that endoplasmic reticulum stress acts upstream of FGF1 release. Thus, the
recently discovered antidiabetes function of FGF1 may act partially through
increasing beta-cell differentiation.
PMID- 26420863
TI - American Diabetes Association and JDRF Research Symposium: Diabetes and the
Microbiome.
AB - From 27-29 October 2014, more than 100 people gathered in Chicago, IL, to
participate in a research symposium titled "Diabetes and the Microbiome," jointly
sponsored by the American Diabetes Association and JDRF. The conference brought
together international scholars and trainees from multiple disciplines, including
microbiology, bioinformatics, endocrinology, metabolism, and immunology, to share
the current understanding of host-microbe interactions and their influences on
diabetes and metabolism. Notably, this gathering was the first to assemble
specialists with distinct expertise in type 1 diabetes, type 2 diabetes,
immunology, and microbiology with the goal of discussing and defining potential
pathophysiologies linking the microbiome and diabetes. In addition to reviewing
existing evidence in the field, speakers presented their own original research to
provide a comprehensive view of the current understanding of the topics under
discussion.Presentations and discussions throughout the conference reflected a
number of important concepts. The microbiota in any host represent a complex
ecosystem with a high degree of interindividual variability. Different microbial
communities, comprising bacteria, archaea, viruses, and fungi, occupy separate
niches in and on the human body. Individually and collectively, these microbes
provide benefits to the host-including nutrient harvest from food and protection
against pathogens. They are dynamically regulated by both host genes and the
environment, and they critically influence both physiology and lifelong health.
The objective of the symposium was to discuss the relationship between the host
and the microbiome-the combination of microbiota and their biomolecular
environment and ecology-specifically with regard to metabolic and immunological
systems and to define the critical research needed to understand and potentially
target the microbiome in the prevention and treatment of diabetes. In this
report, we present meeting highlights in the following areas: 1) relationships
between diabetes and the microbiome, 2) bioinformatic tools, resources, and study
design considerations, 3) microbial programming of the immune system, 4) the
microbiome and energy balance, 5) interventions, and 6) limitations, unanswered
questions, and resource and policy needs.
PMID- 26420865
TI - SPARC triggers a cell-autonomous program of synapse elimination.
AB - Elimination of the excess synaptic contacts established in the early stages of
neuronal development is required to refine the function of neuronal circuits.
Here we investigate whether secreted protein acidic and rich in cysteine (SPARC),
a molecule produced by glial cells, is involved in synapse removal. SPARC
production peaks when innervation of the rat superior cervical ganglion and the
tail of Xenopus tropicalis tadpoles are remodeled. The formation of new
cholinergic synapses in autaptic single-cell microcultures is inhibited by SPARC.
The effect resides in the C-terminal domain, which is also responsible for
triggering a concentration- and time-dependent disassembly of stable cholinergic
synapses. The loss of synaptic contacts is associated with the formation of
retracted axon terminals containing multivesicular bodies and secondary
lysosomes. The biological relevance of in vitro results was supported by
injecting the tail of Xenopus tropicalis tadpoles with peptide 4.2, a 20-aa
sequence derived from SPARC that mimics full-length protein effects. Swimming was
severely impaired at ~5 h after peptide application, caused by the massive
elimination of neuromuscular junctions and pruning of axonal branches. Effects
revert by 6 d after injection, as motor innervation reforms. In conclusion, SPARC
triggers a cell-autonomous program of synapse elimination in cholinergic neurons
that likely occurs when protein production peaks during normal development.
PMID- 26420864
TI - Discriminating direct and indirect connectivities in biological networks.
AB - Reverse engineering of biological pathways involves an iterative process between
experiments, data processing, and theoretical analysis. Despite concurrent
advances in quality and quantity of data as well as computing resources and
algorithms, difficulties in deciphering direct and indirect network connections
are prevalent. Here, we adopt the notions of abstraction, emulation,
benchmarking, and validation in the context of discovering features specific to
this family of connectivities. After subjecting benchmark synthetic circuits to
perturbations, we inferred the network connections using a combination of
nonparametric single-cell data resampling and modular response analysis.
Intriguingly, we discovered that recovered weights of specific network edges
undergo divergent shifts under differential perturbations, and that the
particular behavior is markedly different between topologies. Our results point
to a conceptual advance for reverse engineering beyond weight inference.
Investigating topological changes under differential perturbations may address
the longstanding problem of discriminating direct and indirect connectivities in
biological networks.
PMID- 26420866
TI - Structural and evolutionary relationships of "AT-less" type I polyketide synthase
ketosynthases.
AB - Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I PKS
paradigm. They lack the integrated AT domains within their modules and instead
use a discrete AT that acts in trans, whereas a type I PKS module minimally
contains AT, acyl carrier protein (ACP), and ketosynthase (KS) domains.
Structures of canonical type I PKS KS-AT didomains reveal structured linkers that
connect the two domains. AT-less type I PKS KSs have remnants of these linkers,
which have been hypothesized to be AT docking domains. Natural products produced
by AT-less type I PKSs are very complex because of an increased representation of
unique modifying domains. AT-less type I PKS KSs possess substrate specificity
and fall into phylogenetic clades that correlate with their substrates, whereas
canonical type I PKS KSs are monophyletic. We have solved crystal structures of
seven AT-less type I PKS KS domains that represent various sequence clusters,
revealing insight into the large structural and subtle amino acid residue
differences that lead to unique active site topologies and substrate
specificities. One set of structures represents a larger group of KS domains from
both canonical and AT-less type I PKSs that accept amino acid-containing
substrates. One structure has a partial AT-domain, revealing the structural
consequences of a type I PKS KS evolving into an AT-less type I PKS KS. These
structures highlight the structural diversity within the AT-less type I PKS KS
family, and most important, provide a unique opportunity to study the molecular
evolution of substrate specificity within the type I PKSs.
PMID- 26420867
TI - Regulation of calreticulin-major histocompatibility complex (MHC) class I
interactions by ATP.
AB - The MHC class I peptide loading complex (PLC) facilitates the assembly of MHC
class I molecules with peptides, but factors that regulate the stability and
dynamics of the assembly complex are largely uncharacterized. Based on initial
findings that ATP, in addition to MHC class I-specific peptide, is able to induce
MHC class I dissociation from the PLC, we investigated the interaction of ATP
with the chaperone calreticulin, an endoplasmic reticulum (ER) luminal, calcium
binding component of the PLC that is known to bind ATP. We combined computational
and experimental measurements to identify residues within the globular domain of
calreticulin, in proximity to the high-affinity calcium-binding site, that are
important for high-affinity ATP binding and for ATPase activity. High-affinity
calcium binding by calreticulin is required for optimal nucleotide binding, but
both ATP and ADP destabilize enthalpy-driven high-affinity calcium binding to
calreticulin. ATP also selectively destabilizes the interaction of calreticulin
with cellular substrates, including MHC class I molecules. Calreticulin mutants
that affect ATP or high-affinity calcium binding display prolonged associations
with monoglucosylated forms of cellular MHC class I, delaying MHC class I
dissociation from the PLC and their transit through the secretory pathway. These
studies reveal central roles for ATP and calcium binding as regulators of
calreticulin-substrate interactions and as key determinants of PLC dynamics.
PMID- 26420869
TI - Quantified abundance of magnetofossils at the Paleocene-Eocene boundary from
synchrotron-based transmission X-ray microscopy.
AB - The Paleocene-Eocene boundary (~55.8 million years ago) is marked by an abrupt
negative carbon isotope excursion (CIE) that coincides with an oxygen isotope
decrease interpreted as the Paleocene-Eocene thermal maximum. Biogenic magnetite
(Fe3O4) in the form of giant (micron-sized) spearhead-like and spindle-like
magnetofossils, as well as nano-sized magnetotactic bacteria magnetosome chains,
have been reported in clay-rich sediments in the New Jersey Atlantic Coastal
Plain and were thought to account for the distinctive single-domain magnetic
properties of these sediments. Uncalibrated strong field magnet extraction
techniques have been typically used to provide material for scanning and
transmission electron microscopic imaging of these magnetic particles, whose
concentration in the natural sediment is thus difficult to quantify. In this
study, we use a recently developed ultrahigh-resolution, synchrotron-based, full
field transmission X-ray microscope to study the iron-rich minerals within the
clay sediment in their bulk state. We are able to estimate the total
magnetization concentration of the giant biogenic magnetofossils to be only ~10%
of whole sediment. Along with previous rock magnetic studies on the CIE clay, we
suggest that most of the magnetite in the clay occurs as isolated, near
equidimensional nanoparticles, a suggestion that points to a nonbiogenic origin,
such as comet impact plume condensates in what may be very rapidly deposited CIE
clays.
PMID- 26420868
TI - Neurotransmission plays contrasting roles in the maturation of inhibitory
synapses on axons and dendrites of retinal bipolar cells.
AB - Neuronal output is modulated by inhibition onto both dendrites and axons. It is
unknown whether inhibitory synapses at these two cellular compartments of an
individual neuron are regulated coordinately or separately during in vivo
development. Because neurotransmission influences synapse maturation and circuit
development, we determined how loss of inhibition affects the expression of
diverse types of inhibitory receptors on the axon and dendrites of mouse retinal
bipolar cells. We found that axonal GABA but not glycine receptor expression
depends on neurotransmission. Importantly, axonal and dendritic GABAA receptors
comprise distinct subunit compositions that are regulated differentially by GABA
release: Axonal GABAA receptors are down-regulated but dendritic receptors are up
regulated in the absence of inhibition. The homeostatic increase in GABAA
receptors on bipolar cell dendrites is pathway-specific: Cone but not rod bipolar
cell dendrites maintain an up-regulation of receptors in the transmission
deficient mutants. Furthermore, the bipolar cell GABAA receptor alterations are a
consequence of impaired vesicular GABA release from amacrine but not horizontal
interneurons. Thus, inhibitory neurotransmission regulates in vivo postsynaptic
maturation of inhibitory synapses with contrasting modes of action specific to
synapse type and location.
PMID- 26420870
TI - Mutational analysis of Kaposica reveals that bridging of MG2 and CUB domains of
target protein is crucial for the cofactor activity of RCA proteins.
AB - The complement system has evolved to annul pathogens, but its improper regulation
is linked with diseases. Efficient regulation of the system is primarily provided
by a family of proteins termed regulators of complement activation (RCA). The
knowledge of precise structural determinants of RCA proteins critical for
imparting the regulatory activities and the molecular events underlying the
regulatory processes, nonetheless, is still limited. Here, we have dissected the
structural requirements of RCA proteins that are crucial for one of their two
regulatory activities, the cofactor activity (CFA), by using the Kaposi's sarcoma
associated herpesvirus RCA homolog Kaposica as a model protein. We have scanned
the entire Kaposica molecule by sequential mutagenesis using swapping and site
directed mutagenesis, which identified residues critical for its interaction with
C3b and factor I. Mapping of these residues onto the modeled structure of C3b
Kaposica-factor I complex supported the mutagenesis data. Furthermore, the model
suggested that the C3b-interacting residues bridge the CUB (complement C1r-C1s,
Uegf, Bmp1) and MG2 (macroglobulin-2) domains of C3b. Thus, it seems that
stabilization of the CUB domain with respect to the core of the C3b molecule is
central for its CFA. Identification of CFA-critical regions in Kaposica guided
experiments in which the equivalent regions of membrane cofactor protein were
swapped into decay-accelerating factor. This strategy allowed CFA to be
introduced into decay-accelerating factor, suggesting that viral and human
regulators use a common mechanism for CFA.
PMID- 26420871
TI - Estimation of solid-liquid interfacial tension using curved surface of a soft
solid.
AB - Unlike liquids, for crystalline solids the surface tension is known to be
different from the surface energy. However, the same cannot be said conclusively
for amorphous materials like soft cross-linked elastomers. To resolve this issue
we have introduced here a direct method for measuring solid-liquid interfacial
tension by using the curved surface of a solid. In essence, we have used the
inner surface of tiny cylindrical channels embedded inside a soft elastomeric
film for sensing the effect of the interfacial tension. When a liquid is inserted
into the channel, because of wetting-induced alteration in interfacial tension,
its thin wall deflects considerably; the deflection is measured with an optical
profilometer and analyzed using the Foppl-von Karman equation. We have used
several liquids and cross-linked poly(dimethylsiloxane) as the solid to show that
the estimated values of the solid-liquid interfacial tension matches with the
corresponding solid-liquid interfacial energy reasonably well.
PMID- 26420872
TI - Chemically tunable mucin chimeras assembled on living cells.
AB - Mucins are a family of secreted and transmembrane glycoproteins characterized by
a massive domain of dense O-glycosylation on serine and threonine residues.
Mucins are intimately involved in immunity and cancer, yet elucidation of the
biological roles of their glycodomains has been complicated by their massive
size, domain polymorphisms, and variable glycosylation patterns. Here we
developed a synthetic route to a library of compositionally defined, high
molecular weight, dual end-functionalized mucin glycodomain constructs via N
carboxyanhydride polymerization. These glycopolypeptides are the first synthetic
analogs to our knowledge to feature the native alpha-GalNAc linkage to serine
with molecular weights similar to native mucins, solving a nearly 50-year
synthetic challenge. Physical characterization of the mimics revealed insights
into the structure and properties of mucins. The synthetic glycodomains were end
functionalized with an optical probe and a tetrazine moiety, which allowed site
specific bioorthogonal conjugation to an engineered membrane protein on live
mammalian cells. This strategy in protein engineering will open avenues to
explore the biological roles of cell surface mucins.
PMID- 26420873
TI - Wrinkles and splay conspire to give positive disclinations negative curvature.
AB - Recently, there has been renewed interest in the coupling between geometry and
topological defects in crystalline and striped systems. Standard lore dictates
that positive disclinations are associated with positive Gaussian curvature,
whereas negative disclinations give rise to negative curvature. Here, we present
a diblock copolymer system exhibiting a striped columnar phase that
preferentially forms wrinkles perpendicular to the underlying stripes. In free
standing films this wrinkling behavior induces negative Gaussian curvature to
form in the vicinity of positive disclinations.
PMID- 26420874
TI - CD8 T-cell recognition of acquired alloantigen promotes acute allograft
rejection.
AB - Adaptive CD8 T-cell immunity is the principal arm of the cellular alloimmune
response, but its development requires help. This can be provided by CD4 T cells
that recognize alloantigen "indirectly," as self-restricted allopeptide, but this
process remains unexplained, because the target epitopes for CD4 and CD8 T-cell
recognition are "unlinked" on different cells (recipient and donor antigen
presenting cells (APCs), respectively). Here, we test the hypothesis that the
presentation of intact and processed MHC class I alloantigen by recipient
dendritic cells (DCs) (the "semidirect" pathway) allows linked help to be
delivered by indirect-pathway CD4 T cells for generating destructive cytotoxic
CD8 T-cell alloresponses. We show that CD8 T-cell-mediated rejection of murine
heart allografts that lack hematopoietic APCs requires host secondary lymphoid
tissue (SLT). SLT is necessary because within it, recipient dendritic cells can
acquire MHC from graft parenchymal cells and simultaneously present it as intact
protein to alloreactive CD8 T cells and as processed peptide alloantigen for
recognition by indirect-pathway CD4 T cells. This enables delivery of essential
help for generating cytotoxic CD8 T-cell responses that cause rapid allograft
rejection. In demonstrating the functional relevance of the semidirect pathway to
transplant rejection, our findings provide a solution to a long-standing
conundrum as to why SLT is required for CD8 T-cell allorecognition of graft
parenchymal cells and suggest a mechanism by which indirect-pathway CD4 T cells
provide help for generating effector cytotoxic CD8 T-cell alloresponses at late
time points after transplantation.
PMID- 26420875
TI - Extinction reverses olfactory fear-conditioned increases in neuron number and
glomerular size.
AB - Although much work has investigated the contribution of brain regions such as the
amygdala, hippocampus, and prefrontal cortex to the processing of fear learning
and memory, fewer studies have examined the role of sensory systems, in
particular the olfactory system, in the detection and perception of cues involved
in learning and memory. The primary sensory receptive field maps of the olfactory
system are exquisitely organized and respond dynamically to cues in the
environment, remaining plastic from development through adulthood. We have
previously demonstrated that olfactory fear conditioning leads to increased
odorant-specific receptor representation in the main olfactory epithelium and in
glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction
training specific to the conditioned odor stimulus reverses the conditioning
associated freezing behavior and odor learning-induced structural changes in the
olfactory epithelium and olfactory bulb in an odorant ligand-specific manner.
These data suggest that learning-induced freezing behavior, structural
alterations, and enhanced neural sensory representation can be reversed in adult
mice following extinction training.
PMID- 26420876
TI - Requirement of full TCR repertoire for regulatory T cells to maintain intestinal
homeostasis.
AB - The regulation of intestinal homeostasis by the immune system involves the
dynamic interplay between gut commensal microbiota and resident immune cells. It
is well known that a large and diverse lymphocyte antigen receptor repertoire
enables the immune system to recognize and respond to a wide range of invading
pathogens. There is also an emerging appreciation for a critical role the T-cell
receptor (TCR) repertoire serves in the maintenance of peripheral tolerance by
regulatory T cells (Tregs). Nevertheless, how the diversity of the TCR repertoire
in Tregs affects intestinal homeostasis remains unknown. To address this
question, we studied mice whose T cells express a restricted TCR repertoire. We
observed the development of spontaneous colitis, accompanied by the induction of
T-helper type 17 cells in the colon that is driven by gut commensal microbiota.
We provide further evidence that a restricted TCR repertoire causes a loss of
tolerogenicity to microbiota, accompanied by a paucity of peripherally derived,
Helios(-) Tregs and hyperactivation of migratory dendritic cells. These results
thus reveal a new facet of the TCR repertoire in which Tregs require a diverse
TCR repitoire for intestinal homeostasis, suggesting an additional driving force
in the evolutional significance of the TCR repertoire.
PMID- 26420877
TI - Connectivity Map-based discovery of parbendazole reveals targetable human
osteogenic pathway.
AB - Osteoporosis is a common skeletal disorder characterized by low bone mass leading
to increased bone fragility and fracture susceptibility. In this study, we have
identified pathways that stimulate differentiation of bone forming osteoblasts
from human mesenchymal stromal cells (hMSCs). Gene expression profiling was
performed in hMSCs differentiated toward osteoblasts (at 6 h). Significantly
regulated genes were analyzed in silico, and the Connectivity Map (CMap) was used
to identify candidate bone stimulatory compounds. The signature of parbendazole
matches the expression changes observed for osteogenic hMSCs. Parbendazole
stimulates osteoblast differentiation as indicated by increased alkaline
phosphatase activity, mineralization, and up-regulation of bone marker genes
(alkaline phosphatase/ALPL, osteopontin/SPP1, and bone sialoprotein II/IBSP) in a
subset of the hMSC population resistant to the apoptotic effects of parbendazole.
These osteogenic effects are independent of glucocorticoids because parbendazole
does not up-regulate glucocorticoid receptor (GR) target genes and is not
inhibited by the GR antagonist mifepristone. Parbendazole causes profound
cytoskeletal changes including degradation of microtubules and increased focal
adhesions. Stabilization of microtubules by pretreatment with Taxol inhibits
osteoblast differentiation. Parbendazole up-regulates bone morphogenetic protein
2 (BMP-2) gene expression and activity. Cotreatment with the BMP-2 antagonist
DMH1 limits, but does not block, parbendazole-induced mineralization. Using the
CMap we have identified a previously unidentified lineage-specific, bone anabolic
compound, parbendazole, which induces osteogenic differentiation through a
combination of cytoskeletal changes and increased BMP-2 activity.
PMID- 26420878
TI - ATP11C mutation is responsible for the defect in phosphatidylserine uptake in UPS
1 cells.
AB - Type IV P-type ATPases (P4-ATPases) translocate phospholipids from the exoplasmic
to the cytoplasmic leaflets of cellular membranes. We and others previously
showed that ATP11C, a member of the P4-ATPases, translocates phosphatidylserine
(PS) at the plasma membrane. Twenty years ago, the UPS-1 (uptake of fluorescent
PS analogs) cell line was isolated from mutagenized Chinese hamster ovary (CHO)
K1 cells with a defect in nonendocytic uptake of nitrobenzoxadiazole PS. Due to
its defect in PS uptake, the UPS-1 cell line has been used in an assay for PS
flipping activity; however, the gene(s) responsible for the defect have not been
identified to date. Here, we found that the mRNA level of ATP11C was dramatically
reduced in UPS-1 cells relative to parental CHO-K1 cells. By contrast, the level
of ATP11A, another PS-flipping P4-ATPase at the plasma membrane, or CDC50A, which
is essential for delivery of most P4-ATPases to the plasma membrane, was not
affected in UPS-1 cells. Importantly, we identified a nonsense mutation in the
ATP11C gene in UPS-1 cells, indicating that the intact ATP11C protein is not
expressed. Moreover, exogenous expression of ATP11C can restore PS uptake in UPS
1 cells. These results indicate that lack of the functional ATP11C protein is
responsible for the defect in PS uptake in UPS-1 cells and ATP11C is crucial for
PS flipping in CHO-K1 cells.
PMID- 26420879
TI - Quantitative GSL-glycome analysis of human whole serum based on an EGCase
digestion and glycoblotting method.
AB - Glycosphingolipids (GSLs) are lipid molecules linked to carbohydrate units that
form the plasma membrane lipid raft, which is clustered with sphingolipids,
sterols, and specific proteins, and thereby contributes to membrane physical
properties and specific recognition sites for various biological events. These
bioactive GSL molecules consequently affect the pathophysiology and pathogenesis
of various diseases. Thus, altered expression of GSLs in various diseases may be
of importance for disease-related biomarker discovery. However, analysis of GSLs
in blood is particularly challenging because GSLs are present at extremely low
concentrations in serum/plasma. In this study, we established absolute GSL-glycan
analysis of human serum based on endoglycoceramidase digestion and glycoblotting
purification. We established two sample preparation protocols, one with and the
other without GSL extraction using chloroform/methanol. Similar amounts of GSL
glycans were recovered with the two protocols. Both protocols permitted absolute
quantitation of GSL-glycans using as little as 20 MUl of serum. Using 10 healthy
human serum samples, up to 42 signals corresponding to GSL-glycan compositions
could be quantitatively detected, and the total serum GSL-glycan concentration
was calculated to be 12.1-21.4 MUM. We further applied this method to TLC
prefractionated serum samples. These findings will assist the discovery of
disease-related biomarkers by serum GSL-glycomics.
PMID- 26420880
TI - Site specificity analysis of Piccolo NuA4-mediated acetylation for different
histone complexes.
AB - We have a limited understanding of the site specificity of multi-subunit lysine
acetyltransferase (KAT) complexes for histone-based substrates, especially in
regards to the different complexes formed during nucleosome assembly. Histone
complexes could be a major factor in determining the acetylation specificity of
KATs. In the present study, we utilized a label-free quantitative MS-based method
to determine the site specificity of acetylation catalysed by Piccolo NuA4 on
(H3/H4)2 tetramer, tetramer bound DNA (tetrasome) and nucleosome core particle
(NCP). Our results show that Piccolo NuA4 can acetylate multiple lysine residues
on these three histone complexes, of which NCP is the most favourable, (H3/H4)2
tetramer is the second and tetrasome is the least favourable substrate for
Piccolo NuA4 acetylation. Although Piccolo NuA4 preferentially acetylates histone
H4 (H4K12), the site specificity of the enzyme is altered with different histone
complex substrates. Our results show that before nucleosome assembly is complete,
H3K14 specificity is almost equal to that of H4K12 and DNA-histone interactions
suppress the acetylation ability of Piccolo NuA4. These data suggest that the
H2A/H2B dimer could play a critical role in the increase in acetylation
specificity of Piccolo NuA4 for NCP. This demonstrates that histone complex
formation can alter the acetylation preference of Piccolo NuA4. Such findings
provide valuable insight into regulating Piccolo NuA4 specificity by modulating
chromatin dynamics and in turn manipulating gene expression.
PMID- 26420881
TI - Biological insights into the expression of translation initiation factors from
recombinant CHOK1SV cell lines and their relationship to enhanced productivity.
AB - Translation initiation is on the critical pathway for the production of
monoclonal antibodies (mAbs) by mammalian cells. Formation of a closed loop
structure comprised of mRNA, a number of eukaryotic initiation factors (eIFs) and
ribosomal proteins has been proposed to aid re-initiation of translation and
therefore increase global translational efficiency. We have determined mRNA and
protein levels of the key components of the closed loop, eIFs (eIF3a, eIF3b,
eIF3c, eIF3h, eIF3i and eIF4G1), poly(A)-binding protein (PABP) 1 and PABP
interacting protein 1 (PAIP1), across a panel of 30 recombinant mAb-producing GS
CHOK1SV cell lines with a broad range of growth characteristics and production
levels of a model recombinant mAb. We have used a multi-level statistical
approach to investigate the relationship between key performance indicators (cell
growth and recombinant antibody productivity) and the intracellular amounts of
target translation initiation factor proteins and the mRNAs encoding them. We
show that high-producing cell lines maintain amounts of the translation
initiation factors involved in the formation of the closed loop mRNA, maintaining
these proteins at appropriate levels to deliver enhanced recombinant protein
production. We then utilize knowledge of the amounts of these factors to build
predictive models for and use cluster analysis to identify, high-producing cell
lines. The present study therefore defines the translation initiation factor
amounts that are associated with highly productive recombinant GS-CHOK1SV cell
lines that may be targets for screening highly productive cell lines or to
engineer new host cell lines with the potential for enhanced recombinant antibody
productivity.
PMID- 26420882
TI - Predictive Value Tools as an Aid in Chemopreventive Agent Development.
AB - BACKGROUND: Over 25 years, the National Cancer Institute's Division of Cancer
Prevention has entered some 800 agents into a chemopreventive agent testing
program. Two critical steps involve: 1) in vitro/in vivo morphologic assays and
2) animal tumor assays (incidence/multiplicity reduction). We sought to determine
how accurately the earlier-stage (morphologic) assays predict efficacy in the
later-stage (animal tumor) assays. METHODS: Focusing on 210 agents tested in both
morphologic and animal tumor assays, we carried out statistical modeling of how
well the six most commonly used morphologic assays predicted drug efficacy in
animal tumor assays. Using multimodel inference, three statistical models were
generated to evaluate the ability of these six morphologic assays to predict
tumor outcomes in three different sets of animal tumor assays: 1) all tumor
types, 2) mammary cancer only, and 3) colon cancer only. Using this statistical
modeling approach, each morphologic assay was assigned a value reflecting how
strongly it predicted outcomes in each of the three different sets of animal
tumor assays. RESULTS: We demonstrated differences in the predictive value of
specific morphologic assays for positive animal tumor assay results. Some of the
morphologic assays were strongly predictive of meaningful positive efficacy
outcomes in animal tumor assays representing specific cancer types, particularly
the aberrant crypt focus (ACF) assay for colon cancer. Moreover, less strongly
predictive assays can be combined and sequenced, resulting in enhanced composite
predictive ability. CONCLUSIONS: Predictive models such as these could be used to
guide selection of preventive agents as well as morphologic and animal tumor
assays, thereby improving the efficiency of our approach to chemopreventive agent
development.
PMID- 26420883
TI - How to Rationally Identify Promising Cancer Chemoprevention Agents?
PMID- 26420884
TI - Strokes happen round the clock, but why is stroke care worse on weekends and
overnight?
PMID- 26420885
TI - Does age affect surgical outcomes in patients with degenerative cervical
myelopathy? Results from the prospective multicenter AOSpine International study
on 479 patients.
AB - BACKGROUND: In general, older patients with degenerative cervical myelopathy
(DCM) are felt to have lower recovery potential following surgery due to
increased degenerative pathology, comorbidities, reduced physiological reserves
and age-related changes to the spinal cord. This study aims to determine whether
age truly is an independent predictor of surgical outcome and to provide evidence
to guide practice and decision-making. METHODS: A total of 479 patients with DCM
were prospectively enrolled in the CSM-International study at 16 centres. Our
sample was divided into a younger group (<65 years) and an elderly (>=65 years)
group. A mixed model analytic approach was used to evaluate differences in the
modified Japanese Orthopaedic Association (mJOA), Nurick, Short Form-36 (SF-36)
and Neck Disability Index (NDI) scores between groups. We first created an
unadjusted model between age and surgical outcome and then developed two adjusted
models that accounted for variations in (1) baseline characteristics and (2) both
baseline and surgical factors. RESULTS: Of the 479 patients, 360 (75.16%) were
<65 years and 119 (24.84%) were >=65 years. Elderly patients had a worse
preoperative health status (p<0.0001) and were functionally more severe
(p<0.0001). The majority of younger patients (64.96%) underwent anterior surgery,
whereas the preferred approach in the elderly group was posterior (58.62%,
p<0.0001). Elderly patients had a greater number of decompressed levels than
younger patients (p<0.0001). At 24 months after surgery, younger patients
achieved a higher postoperative mJOA (p<0.0001) and a lower Nurick score
(p<0.0001) than elderly patients. After adjustments for patient and surgical
characteristics, these differences in postoperative outcome scores decreased but
remained significant. CONCLUSIONS: Older age is an independent predictor of
functional status in patients with DCM. However, patients over 65 with DCM still
achieve functionally significant improvement after surgical decompression.
PMID- 26420886
TI - IVIG treatment of mild cognitive impairment due to Alzheimer's disease: a
randomised double-blinded exploratory study of the effect on brain atrophy,
cognition and conversion to dementia.
AB - OBJECTIVE: To determine the effect of intravenous immunoglobulin (IVIG) on brain
atrophy and cognitive function in mild cognitive impairment (MCI) due to
Alzheimer's disease (AD). METHODS: 50 participant 50-84 years of age with
amnestic MCI were administered 0.4 g/kg 10% IVIG or 0.9% saline every 2 weeks for
a total of 5 infusions (2 g/kg total dose) in a randomised double-blinded design.
MRI brain was completed at baseline, 12 and 24 months. Cognitive testing was
completed at baseline and every 4 months. Participants were stratified into early
and late (LMCI) MCI stages. Average annualised per cent change in ventricular
volume was computed as a measure of brain atrophy. RESULTS: There was
significantly less brain atrophy (p=0.037, adjusted for MCI status) in the IVIG
group (5.87%) when compared with placebo (8.14%) at 12 months; at 24 months, the
reduction in brain atrophy no longer reached statistical significance. The LMCI
participants who received IVIG performed better on Alzheimer's Disease Assessment
Scale-cognitive subscale (ADAS-Cog; p=0.011) and Mini-Mental State Examination
(MMSE; p=0.004) at 1 year; these differences were not present after 2 years.
There was no difference in conversion to AD dementia between the treatment and
control groups after 2 years; however, at 1 year, there were fewer conversions
from LMCI to AD dementia in the IVIG group (33.3%) when compared with control
group (58.3%). CONCLUSIONS: This exploratory study provides limited evidence that
a short course of IVIG administered in the MCI stage of AD reduces brain atrophy,
prevents cognitive decline in LMCI and delays conversion to AD dementia for at
least 1 year; however, this effect of IVIG appears to wane by 2 years. TRIAL
REGISTRATION NUMBER: ClinicalTrials.gov, NCT01300728.
PMID- 26420887
TI - FRONTIER Executive Screen: a brief executive battery to differentiate
frontotemporal dementia and Alzheimer's disease.
AB - BACKGROUND AND OBJECTIVE: Executive dysfunctions are a key clinical feature of
behavioural-variant frontotemporal dementia (bvFTD). Such deficits are also found
in Alzheimer's disease (AD), making the differentiation between these two
diseases difficult at times, particularly in the absence of extensive cognitive
assessments. To address this issue, we developed the FRONTIER Executive Screen
(FES), which combines three abbreviated measures of verbal fluency, inhibitory
control and working memory. METHODS: We administered the FES to 28 patients with
dementia (14 bvFTD, 14 AD) matched for disease severity and 33 age-matched and
education-matched healthy controls. We also administered traditional tests of
executive function to establish the concurrent validity of the FES. RESULTS: Both
patient groups obtained lower FES scores (total and subscores) compared to
controls. Correct classification into patient or control groups was reached in
over 90% of study participants based on the FES total score. Only two patients
with bvFTD obtained FES scores within 2 SDs of the control group. Receiver
operating characteristic analyses on the patient groups showed that a cut-off FES
total score of 7/15 achieved 71% sensitivity and 73% specificity for a diagnosis
of bvFTD. In addition, the FES showed high correlations with traditional measures
of executive function. CONCLUSIONS: The FES is a brief (5-10 min) bedside
screening measure which is simple to administer and score, and demonstrates good
discriminative validity to differentiate bvFTD from AD. It is a useful addendum
to general cognitive screening measures and can help with the differential
diagnosis of dementia.
PMID- 26420888
TI - ReCAP: Comparison of Independent Error Checks for Oral Versus Intravenous
Chemotherapy.
AB - PURPOSE: Intravenous (IV) chemotherapy is routinely delivered to patients in
hospital settings, where safeguards such as independent checks and guidelines
govern their administration. In contrast, oral chemotherapy, which is typically
ordered in a cancer center but dispensed and administered in the community and
home, respectively, is subject to fewer controls. Research in the United States
has found that few safeguards in routine use for IV chemotherapy have been
adopted for oral chemotherapy; however, less is known about the Canadian context.
The objective of this study was to determine whether similar safeguards, in the
form of independent checks, existed to identify potential errors related to both
formulations. METHODS: Human factors specialists conducted observations and
interviews in cancer center clinics, a cancer center pharmacy, and four community
pharmacies across Nova Scotia. Processes were analyzed to determine if an
independent check was performed, which qualified provider completed the check,
and at what point of the process the check occurred. RESULTS: A total of 57
systematic checks were identified for IV chemotherapy, whereas only six
systematic checks were identified for oral chemotherapy. Community pharmacists
were the only qualified professionals involved in independent systematic checking
of oral chemotherapy, which occurred during ordering and dispensing. CONCLUSION:
There is an enormous opportunity for pharmacists and other qualified
professionals to take on an expanded role in improving patient safety for oral
chemotherapy. Greater involvement of pharmacists, in both the clinic environment
and the community, would facilitate increased systematic checking, which could
improve patient safety related to oral chemotherapy.
PMID- 26420889
TI - Oncology Care Delivery Reform: Carpe Diem.
PMID- 26420890
TI - ReCAP: Gaps in Insurance Coverage for Pediatric Patients With Acute Lymphoblastic
Leukemia.
AB - PURPOSE: Continuous insurance coverage is an important component of effective
health care. Evaluation of insurance gaps in pediatric cancer care is an
understudied area. METHODS: We conducted a retrospective analysis of payer data
from outpatient oncology encounters at Primary Children's Hospital (Salt Lake
City, UT) over the first 2 years of therapy for pediatric patients with acute
lymphoblastic leukemia diagnosed from 1998 to 2010 (N = 380). Using logistic
regression, we evaluated demographic and clinical predictors (age at diagnosis,
sex, ethnicity, high/standard acute lymphoblastic leukemia risk, and rural/urban
county of residence at diagnosis) of a gap in health insurance. RESULTS: The
median age at diagnosis was 4 years (interquartile range, 3 to 8 years), and 172
patients (45%) were girls. In the first 2 years of treatment, 45 patients (12%)
experienced a gap in health insurance. The odds of having a gap in insurance
coverage decreased by 16% each year from 1998 to 2010 (odds ratio, 0.84; 95% CI,
0.76 to 0.93; test for trend, P = .001). Public insurance at diagnosis was
associated with a four-fold increased likelihood of experiencing an insurance gap
(odds ratio, 4.09; 95% CI, 1.98 to 8.44; P < .001) compared with patients with
private insurance at diagnosis. CONCLUSION: Gaps in insurance coverage during
pediatric cancer treatment are not uncommon, which highlights the importance of
discussing insurance status at diagnosis and throughout a patient's treatment
course to help patients and their families prepare for any changes and avoid
unnecessary financial burden. Future research should focus on examining the
effect of insurance gaps on patient outcomes and evaluating likelihood of gaps in
insurance after health care reform.
PMID- 26420892
TI - Delivering Patient Value by Using Process Improvement Tools to Decrease Patient
Wait Time in an Outpatient Oncology Infusion Unit.
AB - PURPOSE: This study aimed to streamline workflow from arrival to premedication by
decreasing patient wait time to increase value in a high-volume academic
outpatient oncology infusion unit. The streamlining process involved identifying
and prioritizing patients for treatment by driving out waste in patient flow.
METHODS: The plan-do-check-act (PDCA) method and Lean Methodology were used in
completing a project to streamline a defined subset of patient experiences within
an outpatient oncology infusion unit in an academic comprehensive cancer center.
Wait time for patients whose labs were completed before treatment day and within
normal limits and whose orders were signed the day before treatment was collected
manually for a period of 5 months and tracked via value stream and control
charts. RESULTS: Postimplementation, patients experienced a decrease of 17
minutes in mean patient arrival to premedication start time (preimplementation 77
minutes, postimplementation 60 minutes). Additionally, a value stream analysis
demonstrated that in the new process, patient touch points were decreased by two,
and value-added time was increased by 17%. CONCLUSION: By using the systematic
PDCA tool, the team was able to identify opportunities to reduce waste in the
system and streamline patient care. The results demonstrated a significant
improvement in reducing patient wait time from arrival to premedication start
time and increasing percentage of total value added during a patient's treatment
cycle.
PMID- 26420891
TI - Lessons From Early Implementation of a Patient-Centered Care Model in Oncology.
AB - PURPOSE: Oncology practices may serve as the primary health provider for patients
with cancer and the so-called neighbor during periods of transition and
survivorship. New standards for patient-centered oncology practice articulate
expectations for the primary health provider and neighbor roles. We report the
implementation experiences of five oncology practices participating in a pilot of
these standards. METHODS: For each practice, auditors reviewed workflows and
documentation supporting the progress of the practice in meeting the oncology
medical home standards. We also observed clinical encounters and practice
workflow and interviewed clinicians, staff, and patients. RESULTS: Referral
coordination and care management were the most demonstrated functions. The least
commonly demonstrated functions related to tracking and coordination of tests and
medications, as well as quality measurement and improvement. Some opportunities
for structural and process improvement included improving the use of health
information technology, care coordination, quality improvement, telephone triage,
symptom management, patient education, financial counseling, and care team
communication. Making patient-centered care a priority and motivation to change
were cited as facilitators for transformation. CONCLUSION: The pilot oncology
practices had many structures and processes in common, many of which were
established during the early intervention period of this pilot. However, there
was little standardization within and across practices in the way these processes
were established and documented. Establishing structures for care coordination,
quality improvement, and quality measurement should be priorities for practices
considering transformation to a patient-centered model of care.
PMID- 26420893
TI - Teenage suicide today--the facts and figures.
PMID- 26420895
TI - Should chronic metabolic acidosis be treated in older people with chronic kidney
disease?
AB - Metabolic acidosis is common in advanced chronic kidney disease and has been
associated with a range of physiological derangements of importance to the health
of older people. These include associations with skeletal muscle weakness,
cardiovascular risk factors, and bone and mineral disorders that may lead to
fragility fractures. Although metabolic acidosis is associated with accelerated
decline in kidney function, end-stage renal failure is a much less common outcome
in older, frail patients than cardiovascular death. Correction of metabolic
acidosis using bicarbonate therapy is commonly employed, but the existing
evidence is insufficient to know whether such therapy is of net benefit to older
people. Bicarbonate is bulky and awkward to take, may impose additional sodium
load with effects on fluid retention and blood pressure, and may cause
gastrointestinal side effects. Trial data to date suggest potential benefits of
bicarbonate therapy on progression of renal disease and nutrition, but trials
have not as yet been published examining the effect of bicarbonate therapy across
a range of domains relevant to the health of older people. Fortunately, a number
of trials are now underway that should allow us to ascertain whether bicarbonate
therapy can improve physical function, quality of life, and vascular, bone and
kidney health in older people, and hence decide whether any benefits seen
outweigh adverse effects and additional treatment burden in this vulnerable group
of patients.
PMID- 26420894
TI - Genetic loci associated with renal function measures and chronic kidney disease
in children: the Pediatric Investigation for Genetic Factors Linked with Renal
Progression Consortium.
AB - BACKGROUND: Chronic kidney disease (CKD) in children is characterized by rapid
progression and a high incidence of end-stage renal disease and therefore
constitutes an important health problem. While unbiased genetic screens have
identified common risk variants influencing renal function and CKD in adults, the
presence and identity of such variants in pediatric CKD are unknown. METHODS: The
international Pediatric Investigation for Genetic Factors Linked with Renal
Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic
Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and
ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and
Cardiovascular Comorbidity in Children with CKD (4C). Clean genotype data from >
10 million genotyped or imputed single-nucleotide polymorphisms (SNPs) were
available for 1136 patients with measurements of serum creatinine at study
enrollment. Genome-wide association studies were conducted to relate the SNPs to
creatinine-based estimated glomerular filtration rate (eGFR crea) and proteinuria
(urinary albumin- or protein-to-creatinine ratio >= 300 and >= 500 mg/g,
respectively). In addition, European-ancestry PediGFR patients (cases) were
compared with 1347 European-ancestry children without kidney disease (controls)
to identify genetic variants associated with the presence of CKD. RESULTS: SNPs
with suggestive association P-values < 1 * 10(-5) were identified in 10 regions
for eGFR crea, four regions for proteinuria and six regions for CKD including
some plausible biological candidates. No SNP was associated at genome-wide
significance (P < 5 * 10(-8)). Investigation of the candidate genes for
proteinuria in adults from the general population provided support for a region
on chromosome 15 near RSL24D1/UNC13C/RAB27A. Conversely, targeted investigation
of genes harboring GFR-associated variants in adults from the general population
did not reveal significantly associated SNPs in children with CKD. CONCLUSIONS:
Our findings suggest that larger collaborative efforts will be needed to draw
reliable conclusions about the presence and identity of common variants
associated with eGFR, proteinuria and CKD in pediatric populations.
PMID- 26420896
TI - Prognostic relevance of epilepsy at presentation in glioblastoma patients.
AB - BACKGROUND: Epileptogenic glioblastomas are thought to convey a favorable
prognosis, either due to early diagnosis or potential antitumor effects of
antiepileptic drugs. We investigated the relationship between survival and
epilepsy at presentation, early diagnosis, and antiepileptic drug therapy in
glioblastoma patients. METHODS: Multivariable Cox regression was applied to
survival data of 647 consecutive patients diagnosed with de novo glioblastoma
between 2005 and 2013 in order to investigate the association between epilepsy
and survival in glioblastoma patients. In addition, we quantified the association
between survival and valproic acid (VPA) treatment. RESULTS: Epilepsy correlated
positively with survival (HR: 0.75 (95% CI: 0.61-0.92), P < .01). This effect is
independent of age, sex, performance status, type of surgery, adjuvant therapy,
tumor location, and tumor volume, suggesting that this positive correlation
cannot be attributed solely to early diagnosis. For patients who presented with
epilepsy, the use of the antiepileptic drug VPA did not associate with survival
when compared with patients who did not receive VPA treatment. CONCLUSION:
Epilepsy is an independent prognostic factor for longer survival in glioblastoma
patients. This prognostic effect is not solely explained by early diagnosis, and
survival is not associated with VPA treatment.
PMID- 26420898
TI - CPAP Devices for Emergency Prehospital Use: A Bench Study.
AB - BACKGROUND: CPAP is frequently used in prehospital and emergency settings. An air
flow output minimum of 60 L/min and a constant positive pressure are 2 important
features for a successful CPAP device. Unlike hospital CPAP devices, which
require electricity, CPAP devices for ambulance use need only an oxygen source to
function. The aim of the study was to evaluate and compare on a bench model the
performance of 3 orofacial mask devices (Ventumask, EasyVent, and Boussignac CPAP
system) and 2 helmets (Ventukit and EVE Coulisse) used to apply CPAP in the
prehospital setting. METHODS: A static test evaluated air-flow output, positive
pressure applied, and FIO2 delivered by each device. A dynamic test assessed
airway pressure stability during simulated ventilation. Efficiency of devices was
compared based on oxygen flow needed to generate a minimum air flow of 60 L/min
at each CPAP setting. RESULTS: The EasyVent and EVE Coulisse devices delivered
significantly higher mean air-flow outputs compared with the Ventumask and
Ventukit under all CPAP conditions tested. The Boussignac CPAP system never
reached an air-flow output of 60 L/min. The EasyVent had significantly lower
pressure excursion than the Ventumask at all CPAP levels, and the EVE Coulisse
had lower pressure excursion than the Ventukit at 5, 15, and 20 cm H2O, whereas
at 10 cm H2O, no significant difference was observed between the 2 devices.
Estimated oxygen consumption was lower for the EasyVent and EVE Coulisse compared
with the Ventumask and Ventukit. CONCLUSIONS: Air-flow output, pressure applied,
FIO2 delivered, device oxygen consumption, and ability to maintain air flow at 60
L/min differed significantly among the CPAP devices tested. Only the EasyVent and
EVE Coulisse achieved the required minimum level of air-flow output needed to
ensure an effective therapy under all CPAP conditions.
PMID- 26420899
TI - Perception of Asthma Symptoms as Assessed on the Visual Analog Scale in Subjects
With Asthma: A Real-Life Study.
AB - BACKGROUND: The perception of symptoms is a cornerstone in asthma management, but
studies concerning this aspect provide conflicting evidence. The visual analog
scale has been proposed as a useful tool for assessing perception of respiratory
symptoms. The present study investigated whether visual analog scale assessment
of perception of asthma symptoms was correlated to lung function or clinical
features. METHODS: This cross-sectional study enrolled 388 subjects with asthma
(159 males; mean age 39.7 y). Perception of asthma symptoms was assessed by the
visual analog scale; lung function was measured by spirometry. Asthma control was
evaluated by the asthma control test. Anxiety and depression were evaluated on
the Hospital Anxiety and Depression Scale questionnaire. RESULTS: Asthma was well
controlled in 46.6% of subjects. Asthma symptoms in the prior month were reported
by 59% of subjects; asthma signs were detected in 7.2%. The visual analog scale
score was moderately correlated to FEV1 (r = 0.43). Subjects with bronchial
obstruction had lower visual analog scale values than those without (P < .001). A
visual analog scale score of 6 was a reliable cutoff point to discriminate
subjects with bronchial obstruction (area under the curve = 0.71 at receiver
operating characteristic curve; odds ratio [OR] = 7.58). Reported asthma symptoms
(OR = 4.83), asthma signs (OR = 8.36), and anxiety (OR = 1.14) were predictive of
a visual analog scale score of <6. CONCLUSIONS: This real-life study found that
assessment of asthma symptoms by the visual analog scale might be a reliable tool
in managing patients with asthma.
PMID- 26420897
TI - Selective coexpression of VEGF receptor 2 in EGFRvIII-positive glioblastoma cells
prevents cellular senescence and contributes to their aggressive nature.
AB - BACKGROUND: In glioblastoma (GBM), the gene for epidermal growth factor receptor
(EGFR) is frequently amplified. EGFR mutations also are common, including a
truncation mutation that yields a constitutively active variant called EGFR
variant (v)III. EGFRvIII-positive GBM progresses rapidly; however, the reason for
this is not clear because the activity of EGFRvIII is attenuated compared with
EGF-ligated wild-type EGFR. We hypothesized that EGFRvIII-expressing GBM cells
selectively express other oncogenic receptors that support tumor progression.
METHODS: Mining of The Cancer Genome Atlas prompted us to test whether GBM cells
in culture, which express EGFRvIII, selectively express vascular endothelial
growth factor receptor (VEGFR)2. We also studied human GBM propagated as
xenografts. We then applied multiple approaches to test the effects of VEGFR2 on
GBM cell growth, apoptosis, and cellular senescence. RESULTS: In human GBM, EGFR
overexpression and EGFRvIII positivity were associated with increased VEGFR2
expression. In GBM cells in culture, EGFRvIII-initiated cell signaling increased
expression of VEGFR2, which prevented cellular senescence and promoted cell cycle
progression. The VEGFR-selective tyrosine kinase inhibitor cediranib decreased
tumor DNA synthesis, increased staining for senescence-associated beta
galactosidase, reduced retinoblastoma phosphorylation, and increased p27(Kip1),
all markers of cellular senescence. Similar results were obtained when VEGFR2 was
silenced. CONCLUSIONS: VEGFR2 expression by GBM cells supports cell cycle
progression and prevents cellular senescence. Coexpression of VEGFR2 by GBM cells
in which EGFR signaling is activated may contribute to the aggressive nature of
these cells.
PMID- 26420900
TI - Tolerance of Volume Control Noninvasive Ventilation in Subjects With Amyotrophic
Lateral Sclerosis.
AB - BACKGROUND: Noninvasive ventilation (NIV) tolerance has been identified as an
independent predictor of survival in amyotrophic lateral sclerosis (ALS). Volume
control continuous mandatory ventilation (VC-CMV) NIV has been associated with
poor tolerance. The aim of this study was to determine the tolerance of subjects
with ALS to VC-CMV NIV. METHODS: This was a prospective study involving subjects
with ALS who were treated with VC-CMV NIV. Respiratory and functional parameters
were recorded when the subjects began ventilatory support. NIV tolerance was
evaluated after 3 months. RESULTS: Eighty-seven subjects with ALS were included.
After 3 months, 80 subjects (92%) remained tolerant of NIV. Tolerant subjects
presented greater survival (median 22.0 months, 95% CI 14.78-29.21) than
intolerant subjects (median 6.0 months, 95% CI 0.86-11.13) (P = .03). The
variables that best predicted NIV tolerance were mechanically assisted cough peak
flow (P = .01) and percentage of time spent with SpO2 < 90% at night while on NIV
(P = .03) CONCLUSIONS: VC-CMV NIV provides high rates of NIV tolerance in
subjects with ALS. Mechanically assisted cough peak flow and percentage of time
spent with SpO2 < 90% at night while using NIV are the 2 factors associated with
tolerance of VC-CMV NIV in subjects with ALS.
PMID- 26420901
TI - Hypoxemia During Extreme Hyperleukocytosis: How Spurious?
AB - BACKGROUND: Spurious hypoxemia has been described in case reports during extreme
hyperleukocytosis and has led to recommendations for immediate cooling and
analysis of arterial blood gases (ABGs). We sought to determine, in samples
processed as recommended, the magnitude of spurious hypoxemia in acute leukemia
subjects with hyperleukocytosis. METHODS: A retrospective chart review was
conducted of all subjects admitted between 2003 and July 2014 for acute leukemia,
who presented with white blood cell (WBC) count > 50 * 10(9) cells/L and had ABGs
performed. For each ABG, we collected PaO2 , SaO2 , simultaneous WBC count, and
SpO2 when available. Bland and Altman analysis was used to assess the agreement
between SpO2 and SaO2 . RESULTS: One-hundred forty-six samples (from 45 subjects)
were included, of which 57 samples (from 18 subjects) had data available for
Bland and Altman analysis. Mean (SpO2 - SaO2 ) was 2.5%, and 95% CI for limits of
agreement between SpO2 and SaO2 was (-10.1,15.1)%. The mean (SpO2 - SaO2 ) was
significantly higher for WBC count > 100 * 10(9)/L as compared with WBC count <
100 * 10(9)/L (3.8% vs 0.4%, P = .04), and the 95% CIs for limits of agreement
were (-10.3,18)% versus (-7.9,8.6)%. SpO2 and SaO2 were poorly correlated (r(2) =
0.19), whereas the difference (SpO2 - SaO2 ) was fairly correlated with WBC count
(r(2) = 0.44). Overall, 11 of 19 samples with WBC count > 150 * 10(9)/L had PaO2
< 55 mm Hg whereas SpO2 was > 94%, the proportion being 5 of 62 samples for WBC
count < 150 * 10(9)/L (P < .001). Three subjects with WBC count > 150 * 10(9)/L
exhibited large SpO2 to SaO2 differences (10-20%) before leukapheresis, which
decreased to below 5% afterward. CONCLUSIONS: In subjects with acute leukemia and
hyperleukocytosis, despite cooling and quickly analyzing the samples, we observed
poor correlation and agreement between SpO2 and SaO2 , unacceptably low for WBC
count > 100 * 10(9)/L. Our results suggest that current guidelines may not
totally prevent the diagnosis of spurious hypoxemia.
PMID- 26420902
TI - Face Masks for Noninvasive Ventilation: Fit, Excess Skin Hydration, and Pressure
Ulcers.
AB - BACKGROUND: Pressure ulcers (stages III and IV) are serious safety events (ie,
never events). Healthcare institutions are no longer reimbursed for costs to care
for affected patients. Medical devices are the leading cause of pediatric
pressure ulcers. Face masks for noninvasive ventilation were associated with a
high percentage of pressure ulcers at our institution. METHODS: A prospective
cohort study investigated factors contributing to pressure ulcer development in
50 subjects using face masks for noninvasive ventilation. Color imaging, 3
dimensional surface imaging, and skin hydration measurements were used to
identify early skin compromise and evaluate 3 interventions to reduce trauma: (1)
a silicone foam dressing, (2) a water/polyethylene oxide hydrogel dressing, and
(3) a flexible cloth mask. A novel mask fit technique was used to examine the
impact of fit on the potential for skin compromise. RESULTS: Fifty subjects age
10.4 +/- 9.1 y participated with color images for 22, hydration for 34, and mask
fit analysis for 16. Of these, 69% had diagnoses associated with craniofacial
anomalies. Stage I pressure ulcers were the most common injury. Skin hydration
difference was 317 +/- 29 for sites with erythema versus 75 +/- 28 for sites
without erythema (P < .05) and smallest for the cloth mask (P < .05). Fit
distance metrics differed for the nasal, oronasal, and face shield interfaces,
with threshold distances being higher for the oronasal mask than the others (P <
.05). Areas of high contact were associated with skin erythema and pressure
ulcers. CONCLUSIONS: This fit method is currently being utilized to select best
fit masks from available options, to identify the potential areas of increased
tissue pressure, and to prevent skin injuries and their complications.
Improvement of mask fit is an important priority for improving respiratory
outcomes. Strategies to maintain normal skin hydration are important for
protecting tissue integrity.
PMID- 26420903
TI - EFFICIENCY STUDY OF A LEGe DETECTOR SYSTEM FOR THE ASSESSMENT OF 241Am IN SKULL
AT CIEMAT WHOLE BODY COUNTER.
AB - (241)Am incorporation due to an incident or chronic exposure causes an internal
dose, which can be evaluated from the total activity of this isotope in the
skeleton several months after the intake. For this purpose, it is necessary to
perform in vivo measurements of this bone-seeker radionuclide in appropriate
counting bone geometries with very low attenuation of surrounded tissue and to
extrapolate to total activity in the skeleton (ICRP 89, Basic anatomical and
physiological data for use in radiological protection: reference values. 2001.
265). The work here presented refers to direct measurements of americium in the
Cohen skull phantom at the CIEMAT Whole Body Counter (WBC) using low-energy
germanium (LEGe) detectors inside a shielding room. The main goal was to
determinate the most adequate head counting geometry for the in vivo detection of
americium in the bone. The calibration of the in vivo LEGe system was performed
with four detectors with 2 cm of distance to Cohen phantom. Two geometries were
measured, on junction of frontal to parietal bones and frontal bone. The
efficiencies are very similar in both geometries, the preferred counting geometry
is the most comfortable for the person, with the LEGe detectors in the highest
part of the frontal bone, near the junction with the parietal bone, CIEMAT WBC
participated in a skull intercomparison exercise organised by WG7 of EURADOS
(European Radiation Dosimetry Group e.V.). Efficiencies using three different
skull phantoms were obtained. Measurements were performed for different head
counting positions, four of them in the plane of symmetry and others over the
temporal bone. The detector was placed in parallel with the calibration phantom
at a distance of 1 cm. The main gamma emission of (241)Am, 59.5 keV (36 %), was
used for comparing efficiency values. The lower efficiency was obtained over the
frontal and occipital bones. Measurement with one LEGe detector over the parietal
bone is the most efficient. The activity of each skull phantom was calculated
using CIEMAT head calibration. Results of the EURADOS intercomparison are
presented here for discussion.
PMID- 26420904
TI - DEVELOPMENT OF AGE-SPECIFIC JAPANESE PHYSICAL PHANTOMS FOR DOSE EVALUATION IN
INFANT CT EXAMINATIONS.
AB - Secondary to the previous development of age-specific Japanese head phantoms, the
authors designed Japanese torso phantoms for dose assessment in infant computed
tomography (CT) examinations and completed a Japanese 3-y-old head-torso phantom.
For design of age-specific torso phantoms (0, 0.5, 1 and 3 y old), anatomical
structures were measured from CT images of Japanese infant patients. From the CT
morphometry, it was found that rib cages of Japanese infants were smaller than
those in Europeans and Americans. Radiophotoluminescence glass dosemeters were
used for dose measurement of a 3-y-old head-torso phantom. To examine the
validity of the developed phantom, organ and effective doses by the in-phantom
dosimetry system were compared with simulation values in a web-based CT dose
calculation system (WAZA-ARI). The differences in doses between the two systems
were <20 % at the doses of organs within scan regions and effective doses in
head, chest and abdominopelvic CT examinations.
PMID- 26420905
TI - Motivational Interviewing to Increase Cognitive Rehabilitation Adherence in
Schizophrenia.
AB - Adherence to treatment in psychiatric populations is notoriously low. In this
randomized, controlled, proof-of-concept study, we sought to examine whether
motivational interviewing (MI) could be used to enhance motivation for, adherence
to, and benefit obtained from cognitive rehabilitation. Dual diagnosis MI,
developed specifically for individuals with psychotic symptoms and
disorganization, was further adapted to focus on cognitive impairments and their
impact. Sixty-four outpatients diagnosed with schizophrenia spectrum disorders
completed baseline assessments and were randomized to receive either the 2
session MI focused on cognitive functioning or a 2-session sham control interview
focused on assessment and feedback about preferred learning styles. Next, all
participants were given 4 weeks during which they could attend up to 10 sessions
of a computer-based math training program, which served as a brief analog for a
full course of cognitive rehabilitation. As hypothesized, MI condition was
associated with greater increases in task-specific motivation along with greater
training program session attendance. Moreover, postinterview motivation level
predicted session attendance. There were no significant differences in
improvement on a measure of cognitive training content, which may have been due
to the abbreviated nature of the training. While the literature on the efficacy
of MI for individuals with psychosis has been mixed, we speculate that our
positive findings may have been influenced by the adaptations made to MI as well
as the focus on a nonpharmacological intervention.
PMID- 26420906
TI - Synapse and genome: An elusive tete-a-tete.
AB - Two recent papers center on the emerging intersection of DNA methylation and
homeostatic plasticity. To better appreciate the context of these studies, we
first briefly review the mechanistic connections between DNA methylation and
plasticity before delving into the ways in which these two papers fortify the
connection between synapse and nucleus but also highlight the need for studies
with a broader perspective.
PMID- 26420907
TI - The insulin response integrates increased TGF-beta signaling through Akt-induced
enhancement of cell surface delivery of TGF-beta receptors.
AB - Increased activity of transforming growth factor-beta (TGF-beta), which binds to
and stimulates cell surface receptors, contributes to cancer progression and
fibrosis by driving epithelial cells toward a migratory mesenchymal phenotype and
increasing the abundance of extracellular matrix proteins. The abundance of TGF
beta receptors at the cell surface determines cellular responsiveness to TGF
beta, which is often produced by the same cells that have the receptors, and thus
serves as an autocrine signal. We found that Akt-mediated phosphorylation of
AS160, a RabGAP [guanosine triphosphatase (GTPase)-activating protein], promoted
the translocation of TGF-beta receptors from intracellular stores to the plasma
membrane of mouse embryonic fibroblasts and NMuMG epithelial cells. Consequently,
insulin, which is commonly used to treat hyperglycemia and activates Akt
signaling, increased the amount of TGF-beta receptors at the cell surface,
thereby enhancing TGF-beta responsiveness. This insulin-induced increase in
autocrine TGF-beta signaling contributed to insulin-induced gene expression
responses, attenuated the epithelial phenotype, and promoted the migration of
NMuMG cells. Furthermore, the enhanced delivery of TGF-beta receptors at the cell
surface enabled insulin to increase TGF-beta-induced gene responses. The
enhancement of TGF-beta responsiveness in response to Akt activation may help to
explain the biological effects of insulin, the progression of cancers in which
Akt is activated, and the increased incidence of fibroses in diabetes.
PMID- 26420909
TI - Malignant glomus tumor of trachea: a case report with literature review.
AB - Glomus tumors of the trachea are extremely rare and generally benign, with very
few cases of malignant transformation reported in literature. We present the case
of a 74-year-old man explored for cough and dyspnea. Bronchoscopy showed a
polypoid mass arising from the posterolateral tracheal wall. Computed tomography
demonstrated a mid-tracheal tissular mass obliterating the tracheal lumen.
Resection and anastomosis of the trachea were performed. The histological and
immunohistochemical findings were consistent with malignant glomus tumor.
PMID- 26420908
TI - Glutamine-dependent alpha-ketoglutarate production regulates the balance between
T helper 1 cell and regulatory T cell generation.
AB - T cell activation requires that the cell meet increased energetic and
biosynthetic demands. We showed that exogenous nutrient availability regulated
the differentiation of naive CD4(+) T cells into distinct subsets. Activation of
naive CD4(+) T cells under conditions of glutamine deprivation resulted in their
differentiation into Foxp3(+) (forkhead box P3-positive) regulatory T (Treg)
cells, which had suppressor function in vivo. Moreover, glutamine-deprived CD4(+)
T cells that were activated in the presence of cytokines that normally induce the
generation of T helper 1 (TH1) cells instead differentiated into Foxp3(+) Treg
cells. We found that alpha-ketoglutarate (alphaKG), the glutamine-derived
metabolite that enters into the mitochondrial citric acid cycle, acted as a
metabolic regulator of CD4(+) T cell differentiation. Activation of glutamine
deprived naive CD4(+) T cells in the presence of a cell-permeable alphaKG analog
increased the expression of the gene encoding the TH1 cell-associated
transcription factor Tbet and resulted in their differentiation into TH1 cells,
concomitant with stimulation of mammalian target of rapamycin complex 1 (mTORC1)
signaling. Together, these data suggest that a decrease in the intracellular
amount of alphaKG, caused by the limited availability of extracellular glutamine,
shifts the balance between the generation of TH1 and Treg cells toward that of a
Treg phenotype.
PMID- 26420910
TI - Early-onset Streptomyces endocarditis in a prosthetic aortic valve.
AB - A 66-year-old Australian man underwent elective replacement of a severely
stenotic aortic valve with a 22-mm Medtronic-Hall valve. Six weeks later, he was
readmitted with worsening dyspnea, fever, and mild anemia. Investigations
confirmed pulmonary edema and moderate periprosthetic aortic regurgitation. The
pulmonary edema was managed conservatively, and a second 22-mm Medtronic-Hall
valve was implanted. Infective endocarditis was suspected in the aortic annulus
below the orifice of the right coronary artery. A bacteriological study revealed
a rare bacteria of Streptomyces species. The patient received intensive
antibiotic therapy over a 6-week period of hospitalization, and the aortic
regurgitation disappeared one week postoperatively.
PMID- 26420911
TI - The Collapse and Expansion of Liquid-Filled Elastic Channels and Cracks.
AB - The rate at which fluid drains from a collapsing channel or crack depends on the
interaction between the elastic properties of the solid and the fluid flow. The
same interaction controls the rate at which a pressurized fluid can flow into a
crack. In this paper, we present an analysis for the interaction between the
viscous flow and the elastic field associated with an expanding or collapsing
fluid-filled channel. We first examine an axisymmetric problem for which a
completely analytical solution can be developed. A thick-walled elastic cylinder
is opened by external surface tractions, and its core is filled by a fluid. When
the applied tractions are relaxed, a hydrostatic pressure gradient drives the
fluid to the mouth of the cylinder. The relationship between the change in
dimensions, time, and position along the cylinder is given by the diffusion
equation, with the diffusion coefficient being dependent on the modulus of the
substrate, the viscosity of the fluid, and the ratio of the core radius to the
exterior radius of the cylinder. The second part of the paper examines the
collapse of elliptical channels with arbitrary aspect ratios, so as to model the
behavior of fluid-filled cracks. The channels are opened by a uniaxial tension
parallel to their minor axes, filled with a fluid, and then allowed to collapse.
The form of the analysis follows that of the axisymmetric calculations, but is
complicated by the fact that the aspect ratio of the ellipse changes in response
to the local pressure. Approximate analytical solutions in the form of the
diffusion equation can be found for small aspect ratios. Numerical solutions are
given for more extreme aspect ratios, such as those appropriate for cracks. Of
particular note is that, for a given cross-sectional area, the rate of collapse
is slower for larger aspect ratios. With minor modifications to the initial
conditions and the boundary conditions, the analysis is also valid for cracks
being opened by a pressurized fluid.
PMID- 26420912
TI - Role of MALAT1 as a Prognostic Factor for Survival in Various Cancers: A
Systematic Review of the Literature with Meta-Analysis.
AB - OBJECTIVES: The expression of metastasis-associated lung adenocarcinoma
transcript 1 (MALAT1), a highly abundant and ubiquitously expressed long
noncoding RNA (lncRNA), influences clinical parameters and may have prognostic
value in cancer. This meta-analysis evaluated the prognostic role of MALAT1 in
various cancers. MATERIALS AND METHODS: Systematic literature searches of PubMed
and EMBASE databases were conducted for eligible studies of the prognostic role
of MALAT1 in cancer. Overall survival (OS), disease-specific survival (DSS), and
disease-free survival (DFS) were analyzed. Summary hazard ratios (HRs) and 95%
confidence intervals (95% CIs) were assessed to evaluate the influence of MALAT1
expression on patient prognosis. RESULTS: Nine studies with a total of 932
patients were included in the analysis. Elevated MALAT1 expression was
significantly correlated with poor OS (HR 2.02; 95% CI: 1.62-2.52; P < 0.001;
I(2) = 0%). Subgroup analysis indicated that tumor type, histology type,
ethnicity, and measurement technique did not affect the prognostic value of
MALAT1 for OS. The HR of elevated MALAT1 for DFS was 2.78 (95% CI: 1.87-4.15; P <
0.001; I(2) = 0%). CONCLUSIONS: Elevated MALAT1 expression is correlated with
poor OS in various types of cancer, suggesting that this gene is a prognostic
factor for different types of cancer.
PMID- 26420914
TI - Serum and Vitreous Concentrations of Omentin-1 in Diabetic Retinopathy.
AB - OBJECTIVE: Omentin, a new discovered adipokine, is implicated to inhibit
inflammation. Inflammation is one important mechanism of diabetic retinopathy
(DR). The purpose of this work was to evaluate serum and vitreous concentrations
of omentin-1 in patients with diabetic retinopathy (DR). METHODS: This study
enrolled 204 diabetic patients (60 without DR, 49 with NPDR, and 95 with PDR) and
65 control subjects. RESULTS: Serum and vitreous omentin-1 levels in PDR patients
were markedly decreased compared with those in the other three groups. NPDR
patients showed reduced vitreous omentin-1 compared with patients without DR. In
addition, control subjects had significantly higher levels of serum and vitreous
omentin-1 compared with diabetic patients without DR, NPDR patients, and PDR
patients. In addition, serum/vitreous omentin-1 ratio was positively correlated
with the development and severity of DR. CONCLUSION: Serum and vitreous omentin-1
levels, as well as serum/vitreous omentin-1 ratio, are correlated with the
presence and severity of DR.
PMID- 26420913
TI - Activated Complement Factors as Disease Markers for Sepsis.
AB - Sepsis is a leading cause of death in the United States and worldwide. Early
recognition and effective management are essential for improved outcome. However,
early recognition is impeded by lack of clinically utilized biomarkers.
Complement factors play important roles in the mechanisms leading to sepsis and
can potentially serve as early markers of sepsis and of sepsis severity and
outcome. This review provides a synopsis of recent animal and clinical studies of
the role of complement factors in sepsis development, together with their
potential as disease markers. In addition, new results from our laboratory are
presented regarding the involvement of the complement factor, mannose-binding
lectin, in septic shock patients. Future clinical studies are needed to obtain
the complete profiles of complement factors/their activated products during the
course of sepsis development. We anticipate that the results of these studies
will lead to a multipanel set of sepsis biomarkers which, along with currently
used laboratory tests, will facilitate earlier diagnosis, timely treatment, and
improved outcome.
PMID- 26420916
TI - The Surgical Management of Concomitant Gallbladder and Common Bile Duct Stones.
AB - Background. The management of choledocholithiasis has evolved from open common
bile duct exploration (OCBDE) to therapeutic endoscopic retrograde
cholangiopancreatography (ERCP) to laparoscopic common bile duct exploration
(LCBDE). Each entails a degree of difficulty. Aim. To review 5-year results of
bile duct exploration in an UGI unit. Methods. Common bile duct explorations
(CBDEs) performed between January 2008 and January 2013 were identified from a
prospectively collected clinical audit system and results reviewed
retrospectively. Results. 216 CBDEs were performed, 119 (55%) as an emergency and
52 (24%) following failed ERCP. Open CBDE (OCBDE) was performed primarily in
34/216 (16%) patients and attempted laparoscopically in 182 (84%). Fifty nine
(32%) Laparoscopic CBDEs (LCBDEs) were converted to OCBDE. Of the remaining 123
LCBDEs, 51 (41%) primary choledochotomies and 72 (59%) primary transcystic CBDEs
(TC-CBDEs) were performed. Forty nine (68%) TC-CBDEs were considered successful
and 23 (32%) failed. Fifteen failed TC-CBDEs were converted to a successful
laparoscopic choledochotomy. Ductal clearance was achieved in 187/216 (87%)
patients and retained stones were identified in 20/123 (16%) LCBDEs.
Complications occurred in 52/216 (24%) patients. There were 8/216 (4%) bile leaks
requiring further intervention. Postoperative ERCP was carried out in 32/216
(15%) patients and 9/216 (4%) required relaparoscopy/laparotomy. No patient died.
Conclusions. Successful management of choledocholithiasis requires a breadth of
laparoscopic and endoscopic expertise.
PMID- 26420917
TI - A molecular modeling based screening for potential inhibitors to alpha hemolysin
from Staphylococcus aureus.
AB - Staphylococcus aureus, a Gram-positive bacterium is pathogenic in nature. It is
known that secreted toxins remain active after antibiotic treatment. The alpha
hemolysin or alpha toxin damages cell membrane and induces apoptosis and
degradation of DNA. The titer of alphahemolysin increases and causes hemostasis
disturbances, thrombocytopenia, and pulmonary lesions during staphylococcal
infection. Therefore, it is of interest to inhibit alpha hemolysin using novel
compounds. We used the structure of alpha hemolysin(PDB: 7AHL) to screen
structures for 100,000 compounds from the ZINC database using molecular docking
with AutoDock VINA. Nine (9) successive hits were then subjected for
pharmacokinetic and toxicity properties by PROTOX (a webserver for the prediction
of oral toxicities of small molecules) and FAFDrugs (a tool for prediction of
ADME and Toxicity). This exercise further identified hit #1 ({[3a
(Dihydroxymethyl)-6-hydroxy-2,2-dimethyl-1,3,4-trioxatetrahydro-2H-pentalen-5-
yl]methyl}amino(9H-fluoren-9-yl)acetate with binding affinity: -10.3 kcal/mol)
and hit #2 (6-(Dihydroxymethyl)-2-{2-[3- (methylamino)propyl]-2
azatricyclo[9.4.0.03,8]pentadeca-1(11),3,5,7,12,14-hexaen-6-yloxy}tetrahydro-2H
pyran-3,4,5-triol with binding affinity: -9.6 kcal/mol) with acceptable toxicity
and ADME properties for potential predicted hemolysin inhibition. These compounds
should then be evaluated in vitro using inhibitory studies.
PMID- 26420918
TI - Molecular Docking and Pharmacological Investigations of Rivastigmine-Fluoxetine
and Coumarin-Tacrine hybrids against Acetyl Choline Esterase.
AB - The present AChE inhibitors have been successful in the treatment of Alzheimer's
Diseases however suffers serious side effects. Therefore in this view, the
present study was sought to identify compounds with appreciable pharmacological
profile targeting AChE. Analogue of Rivastigmine and Fluoxetine hybrid
synthesized by Toda et al, 2003 (dataset1), and Coumarin-Tacrine hybrids
synthesized by Qi Sun et al (dataset2) formed the test compounds for the present
pharmacological evaluation. p-cholorophenyl substituted Rivastigmine and
Fluoxetine hybrid compound (26d) from dataset 1 and -OCH3 substitute Coumarin
Tacrine hybrids (1h) from dataset 2 demonstrated superior pharmacological
profile. 26 d showed superior pharmacological profile comparison to the entire
compounds in either dataset owing to its better electrostatic interactions and
hydrogen bonding patterns. In order to identify still better compound with
pharmacological profile than 26 d and 1h, virtual screening was performed. The
best docked compound (PubCId: PubCid: 68874404) showed better affinity than its
parent 26 d, however showed poor ADME profile and AMES toxicity. CHEMBL2391475
(PubCid: 71699632) similar to 1h had reduced affinity in comparison to its parent
compound 1h. From, our extensive analysis involving binding affinity analysis,
ADMET properties predictions and pharmacophoric mappings, we report p
cholorophenyl substituted rivastigmine and fluoxetine hybrid (26d) to be a
potential candidate for AcHE inhibition which in addition can overcome narrow
therapeutic window of present AChE inhibitors in clinical treatment of
Alzheimer's disease. ABBREVIATIONS: AD - Alzheimer's Disease, AChE - Acetyl
Choline Estarase, OPLS - Optimized Potentials for Liquid Simulations, PDB -
Protein Data Bank.
PMID- 26420919
TI - Curcumin binds in silico to anti-cancer drug target enzyme MMP-3 (human
stromelysin-1) with affinity comparable to two known inhibitors of the enzyme.
AB - In silico interaction of curcumin with the enzyme MMP-3 (human stromelysin-1) was
studied by molecular docking using AutoDock 4.2 as the docking software
application. AutoDock 4.2 software serves as a valid and acceptable docking
application to study the interactions of small compounds with proteins.
Interactions of curcumin with MMP-3 were compared to those of two known
inhibitors of the enzyme, PBSA and MPPT. The calculated free energy of binding
(DeltaG binding) shows that curcumin binds with affinity comparable to or better
than the two known inhibitors. Binding interactions of curcumin with active site
residues of the enzyme are also predicted. Curcumin appears to bind in an
extendended conformation making extensive VDW contacts in the active site of the
enzyme. Hydrogen bonding and pi-pi interactions with key active site residues is
also observed. Thus, curcumin can be considered as a good lead compound in the
development of new inhibitors of MMP-3 which is a potential target of anticancer
drugs. The results of these studies can serve as a starting point for further
computational and experimental studies.
PMID- 26420920
TI - Modelling and Characterization of Glial Fibrillary Acidic Protein.
AB - Glial Fibrillary Acidic Protein (GFAP) is an intermediate-filament (IF) protein
that maintains the astrocytes of the Central Nervous System in Human. This is
differentially expressed during serological studies in inflamed condition such as
Rheumatoid Arthritis (RA). Therefore, it is of interest to glean molecular
insight using a model of GFAP (49.88 kDa) due to its crystallographic
nonavailability. The present study has been taken into consideration to construct
computational protein model using Modeller 9.11. The structural relevance of the
protein was verified using Gromacs 4.5 followed by validation through PROCHECK,
Verify 3D, WHAT-IF, ERRAT and PROVE for reliability. The constructed three
dimensional (3D) model of GFAP protein had been scrutinized to reveal the
associated functions by identifying ligand binding sites and active sites.
Molecular level interaction study revealed five possible surface cavities as
active sites. The model finds application in further computational analysis
towards drug discovery in order to minimize the effect of inflammation.
PMID- 26420915
TI - Syndecan-1 in Cancer: Implications for Cell Signaling, Differentiation, and
Prognostication.
AB - Syndecan-1, a cell surface heparan sulfate proteoglycan, is critically involved
in the differentiation and prognosis of various tumors. In this review, we
highlight the synthesis, cellular interactions, and the signalling pathways
regulated by syndecan-1. The basal syndecan-1 level is also crucial for
understanding the sequential changes involving malignant transformation, tumor
progression, and advanced or disseminated cancer stages. Moreover, we focus on
the cellular localization of this proteoglycan as cell membrane anchored and/or
shed, soluble syndecan-1 with stromal or nuclear accumulation and how this may
carry different, highly tissue specific prognostic information for individual
tumor types.
PMID- 26420921
TI - Pharmacophore Modeling and Molecular Docking Studies of potential inhibitors to
E6 PBM-PDZ from Human Papilloma Virus (HPV).
AB - High-risk human papillomaviruses (HPVs) are known to cause cervical cancer.
Vaccines are now available to prevent HPV infection. However, a clinically
approved drug is yet not available to treat HPV. The PDZ(PSD-95/Dlg/ZO-1)-binding
motif (PBM) in the E6 protein of HPVs targets the PDZ domain (known to be
associated with oncogenesis) for degradation. Therefore, it is of interest to
study PBM-PDZ interaction towards its possible inhibition with a potential
inhibitor. Thus, four pharmocophore models of PBM-PDZ complex were developed. In
order to obtain potent small molecules for its inhibition, a commercial compound
database was screened using both these pharmacophore models and molecule docking
method. These efforts identified four potential compounds (1-4) towards its
inhibition with the docking scores range -18.2 to -15.0.
PMID- 26420922
TI - Codon bias and gene expression of mitochondrial ND2 gene in chordates.
AB - BACKGROUND: Mitochondrial ND gene, which encodes NADH dehydrogenase, is the first
enzyme of the mitochondrial electron transport chain. Leigh syndrome, a
neurodegenerative disease caused by mutation in the ND2 gene (T4681C), is
associated with bilateral symmetric lesions in basal ganglia and subcortical
brain regions. Therefore, it is of interest to analyze mitochondrial DNA to glean
information for evolutionary relationship. This study highlights on the analysis
of compositional dynamics and selection pressure in shaping the codon usage
patterns in the coding sequence of MT-ND2 gene across pisces, aves and mammals by
using bioinformatics tools like effective number of codons (ENC), codon
adaptation index (CAI), relative synonymous codon usage (RSCU) etc. RESULTS: We
observed a low codon usage bias as reflected by high ENC values in MT-ND2 gene
among pisces, aves and mammals. The most frequently used codons were ending with
A/C at the 3(rd) position of codon and the gene was AT rich in all the three
classes. The codons TCA, CTA, CGA and TGA were over represented in all three
classes. The F1 correspondence showed significant positive correlation with G, T3
and CAI while the F2 axis showed significant negative correlation with A and T
but significant positive correlation with G, C, G3, C3, ENC, GC, GC1, GC2 and
GC3. CONCLUSIONS: The codon usage bias in MTND2 gene is not associated with
expression level. Mutation pressure and natural selection affect the codon usage
pattern in MT-ND 2 gene.
PMID- 26420923
TI - ADSBET2: Automated Determination of Salt-Bridge Energy-Terms version 2.
AB - Component (bridge: DeltaDeltaGbrd , background: DeltaDeltaGprot , desolvation:
DeltaDeltaGdsolv ) and net (DeltaDeltaGnet ) energy-terms of salt-bridge
structure (SBS) are auto-generated by the program ADSBET that makes use of
general purpose Adaptive Poison Boltzmann Solver (APBS) method. While the
procedure reports gross energy terms (Kcal Mol(-1) ), report on bond-multiplicity
corrected normalized energyterms (Kcal Mol(-1) Bond(-1) ) along with their
accessibility (ASA) in monomer, isolated-SBS (ISBS) and networked-SBS (NSBS)
format would be very useful for statistical comparison among SBSs and
understanding their location in protein structure. In this end, ADSBET2
potentially incorporates these features along with additional model for side
chain. Gross and normalized energy-terms are redirected in monomer, ISBS and NSBS
format along with their ASA informations. It works on any number of SBSs for any
number of structure files present in a database. Taken together, ADSBET2 has been
suitable for statistical analyses of SBSs energetics and finds applications in
protein engineering and structural bioinformatics. AVAILABILITY: ADSBET2 is
freely available at http://sourceforge.net/projects/ADSBET2/ for all users.
PMID- 26420924
TI - NNvPDB: Neural Network based Protein Secondary Structure Prediction with PDB
Validation.
AB - The predicted secondary structural states are not cross validated by any of the
existing servers. Hence, information on the level of accuracy for every sequence
is not reported by the existing servers. This was overcome by NNvPDB, which not
only reported greater Q3 but also validates every prediction with the homologous
PDB entries. NNvPDB is based on the concept of Neural Network, with a new and
different approach of training the network every time with five PDB structures
that are similar to query sequence. The average accuracy for helix is 76%, beta
sheet is 71% and overall (helix, sheet and coil) is 66%. AVAILABILITY:
http://bit.srmuniv.ac.in/cgi-bin/bit/cfpdb/nnsecstruct.pl.
PMID- 26420925
TI - Platelet-rich plasma therapy: A novel application in regenerative medicine.
PMID- 26420926
TI - Hemolysis: A positive agglutination reaction while studying titration of anti A/B
antibody for ABO-incompatible solid organ transplants.
PMID- 26420928
TI - Comprehensive analysis of changes in clinically significant divalent serum cation
levels during automated plateletpheresis in healthy donors in a tertiary care
center in North India.
AB - BACKGROUND: Adverse effects due to apheresis are unusual. The most common
apheresis-specific reaction is hypocalcemia due to citrate anticoagulation and
induces ionized hypocalcemia and hypomagnesemia by chelating effect during the
plateletpheresis; generally transient and self-limiting but has the potential of
severely injuring donor. We have investigated total calcium (tCa(++)) and
magnesium (tMg(++)) levels in sixty healthy plateletpheresis donors at different
intervals during the procedure and 30 min post-procedure. MATERIALS AND METHODS:
A total of 60 procedures were performed on healthy donors. Blood samples were
obtained from sterile diversion pouch placed on apheresis circuit. 5 ml sample in
plain vials was obtained at different intervals during each procedure and 30 min
after the end of the procedure. Samples were used for measurement of tCa(++) and
tMg(++) levels. RESULTS: There is continuous decrease in mean tCa(++) from
baseline levels (9.83 +/- 0.64 mg/dl) till end of procedure (8.33 +/- 0.78
mg/dl), but after 30 min, levels again reached near their respective baseline
values (9.42 +/- 0.54 mg/dl). Similarly, mean tMg(++) fell from baseline levels
(2.36 +/- 0.3 mg/dl) till the end of procedure (1.39 +/- 0.40 mg/dl). After 30
min, levels were again increased, their respective baseline values (2.25 +/- 0.25
mg/dl). CONCLUSION: There is continuous, gradual, and significant fall (P < 0.05)
in mean tCa(++) and mean tMg(++) from baseline levels to till the end of
procedure but after 30 min of completion of procedure, levels again reached near
their respective baseline values.
PMID- 26420927
TI - Current trends in platelet transfusions practice: The role of ABO-RhD and human
leukocyte antigen incompatibility.
AB - Platelet transfusions have contributed to the revolutionary modern treatment of
hypoproliferative thrombocytopenia. Despite the long-term application of platelet
transfusion in therapeutics, all aspects of their optimal use (i.e., in cases of
ABO and/or Rh (D incompatibility) have not been definitively determined yet. We
reviewed the available data on transfusion practices and outcome in ABO and RhD
incompatibility and platelet refractoriness due to anti-human leukocyte antigen
(HLA) antibodies. Transfusion of platelets with major ABO-incompatibility is
related to reduced posttransfusion platelet (PLT) count increments, compared to
ABO-identical and minor, but still are equally effective in preventing clinical
bleeding. ABO-minor incompatible transfusions pose the risk of an acute hemolytic
reaction of the recipient that is not always related to high anti-A, B donor
titers. ABO-identical PLT transfusion seems to be the most effective and safest
therapeutic strategy. Exclusive ABO-identical platelet transfusion policy could
be feasible, but alternative approaches could facilitate platelet inventory
management. Transfusion of platelets from RhD positive donors to RhD negative
patients is considered to be effective and safe though is associated with low
rate of anti-D alloimmunization due to contaminating red blood cells. The
prevention of D alloimmunization is recommended only for women of childbearing
age. HLA alloimmunization is a major cause of platelet refractoriness. Managing
patients with refractoriness with cross-matched or HLA-matched platelets is the
current practice although data are still lacking for the efficacy of this
practice in terms of clinical outcome. Leukoreduction contributes to the
reduction of both HLA and anti-D alloimmunization.
PMID- 26420929
TI - Bombay blood group: Is prevalence decreasing with urbanization and the decreasing
rate of consanguineous marriage.
AB - CONTEXT: Bombay blood group although rare is found to be more prevalent in the
Western and Southern states of India, believed to be associated with
consanguineous marriage. AIMS: To estimate the prevalence of the Bombay blood
group (Oh) in the urban population of Puducherry. To find the effect of
urbanization on consanguineous marriage and to establish whether consanguinity
plays a part in the prevalence of Oh group. To compare Oh group prevalence with
that of other neighboring states, where population is not predominantly urban.
SETTINGS AND DESIGN: This is a descriptive study in a tertiary care hospital in
Puducherry, over a period of 6 years. MATERIALS AND METHODS: All blood samples
showing 'O' group were tested with anti-H lectin. Specialized tests like
Adsorption Elution Technique, inhibition assay for determination of secretor
status were performed on Oh positive cases. Any history of consanguineous
marriage was recorded. STATISTICAL ANALYSIS USED: All variables were categorical
variable and percentage and proportions were calculated manually. RESULTS:
Analysis of the results of 35,497 study subjects showed that the most common
group was 'O' group constituting 14,164 (39.90%) of subjects. Only three "Oh"
that is, Bombay phenotype (0.008%) were detected. Consanguinity was observed in
two cases (66.66%). CONCLUSIONS: This study shows the prevalence of Bombay blood
group representing the urban population of Puducherry, to be high (0.008%) and
associated with consanguineous marriage (66.66%). Thus, consanguinity is still an
important risk factor present, even in an urban population in Southern India.
PMID- 26420930
TI - Frequencies of human neutrophil antigen-4 and human neutrophil antigen-5 among
Thai blood donors.
AB - CONTEXT: Antibodies against human neutrophil antigens (HNAs) are implicated in
immune-mediated neutropenia, transfusion-related acute lung injury and febrile
transfusion reactions. AIMS: This study aimed to determine HNA gene frequencies
of the HNA-4 and HNA-5 systems among Thai populations and compare these
frequencies with those previously reported for other populations. MATERIALS AND
METHODS: 800 DNA samples obtained from 500 unrelated healthy blood donors from
Bangkok and 300 samples from Chiang Mai, Thailand were included. Samples were
typed for each HNA allele including HNA-4a, HNA-4b, HNA-5a, and HNA-5b using an
in-house polymerase chain reaction with sequence-specific primer technique.
RESULTS: The frequencies of HNA-4a and HNA-4b alleles in central Thais were 0.975
and 0.025, respectively and for Northern Thais, their frequencies were 0.965 and
0.035, respectively. For HNA-5a and HNA-5b alleles, their frequencies were 0.771
and 0.229; 0.748, and 0.252 in central and Northern Thais, respectively. The
frequencies of HNA-4 and HNA-5 systems in central Thais are closely related to
those in Northern Thais (P > 0.05). However, their frequencies were different
from other populations (P < 0.001), except HNA-5a and HNA-5b gene frequencies in
Thais were similar to Caucasians (P > 0.05). CONCLUSION: This study could
contribute to predict the risk of alloimmunization to HNA-4 and HNA-5 systems,
especially in feto-maternal incompatibility in Thais.
PMID- 26420931
TI - Seroprevalence of hepatitis B virus infection and hepatitis B surface antibody
status among laboratory health care workers in Isfahan, Iran.
AB - BACKGROUND: Laboratory health care workers (HCWs) may become infected through
their occupation with blood-borne pathogens. The aims of this study were
determining the seroprevalence of hepatitis B virus (HBV) and the protection
offered by HBV vaccine in medical laboratory HCWs. MATERIALS AND METHODS: A
descriptive cross-sectional study was carried out on 203 employers of clinical
laboratories. Participant data were obtained through a questionnaire, and the
level of antigens and antibodies were measured by enzyme-linked immunosorbent
assay (ELISA). RESULTS: All of the subjects were negative for HBV infection.
Forty-seven (23.2%) were not immune, 126 (62.0%) were relatively immune, and 30
(14.8%) were highly immune. CONCLUSION: Hepatitis B infection is infrequent in
laboratory HCWs in Isfahan.
PMID- 26420932
TI - Unusual spontaneous cold auto-hemagglutination phenomenon in blood units stored
under blood bank condition: A retrospective analysis.
AB - BACKGROUND: Cold agglutinins (CA) are benign naturally occurring low titer
autoantibodies present in most individuals. Those with moderate strength are
found in infections, malignancies or autoimmune conditions with diagnostic
importance. AIM: Present report deals with CA that brought spontaneous
hemagglutination in blood units stored at 2-6 degrees C. STUDY DESIGN: Over 32
months period between July 1993 and December 1995, blood units were inspected for
spontaneous cold auto-hemagglutination (SpCA) phenomenon. The plasma from these
units was separated and investigated for serological specificity using in house
red cell panel and standard serological methods. RESULTS: Among 51,671 blood
units, 112 units showed SpCA phenomenon. A rising trend seen in first half of
study period significantly fell in remaining half. Specificities of the
antibodies detected include anti-I (27), anti-i (53), anti-Pr (21) with remaining
few being undetermined specificity. Absorption of serum using enzyme-treated red
cells revealed a presence of anti-Pr among the cases, the two of which with new
specificities that reacted preferentially with red cells from either new-born or
adults and were tentatively named as anti-Pr(Fetal) and anti-Pr(adult),
respectively. While 9 cases showed optimum reaction at neutral pH of 7, 68 (62%)
cases reacted at pH 5.8 through 8.0, 28 (26%) cases preferred an acidic pH 5.8
and 4 cases opted an alkaline pH 8. Of 28 cases with antibodies preferentially
reacting in acidic medium, 17 (60%) cases were anti-i and 7 (25%) cases were anti
Pr. CONCLUSION: Unique SpCA phenomenon observed in blood units stored under blood
bank conditions seems to be due to CA developed in response to vector-borne
infectious agents. Majority of the cases displayed their specificities, otherwise
are rare to be encountered.
PMID- 26420933
TI - Release of cytokines in stored whole blood and red cell concentrate: Effect of
leukoreduction.
AB - BACKGROUND: Storage time of blood components plays a major role in the
accumulation of cytokines causing adverse transfusion reactions. AIMS: The aim
was to study the trend in the levels of interleukin-6 (IL-6), IL-8, tumor
necrosis factor-alpha (TNF-alpha) and regulated upon activation, normal T-cells
expressed and secreted (RANTES) during storage of whole blood (WB) and red cell
concentrate (RCC) and to study the effect of leukoreduction (LR). MATERIALS AND
METHODS: WB sample was taken on 0, 7, 14, 21, and between 28 and 35 days and
plasma aliquots were frozen. Samples from RCC and buffy-coat depleted RCC
prepared using Optipress II were collected on 0, 7, 14, 21 and between 28 and 35
days. Cytokine estimation was done using ELISA development kits. Normal range of
cytokines was established using 0 day samples of WB. Statistical analysis was
done using nonparametric tests. RESULTS AND CONCLUSION: The normal range of IL-6
was 0-23 pg/ml, IL-8 0-12 pg/ml, TNF-alpha 0-3 pg/ml, and RANTES 1200-2000 pg/ml.
IL-6 was in normal range and showed a decreasing trend during storage. IL-8
levels increased significantly from 0 to 35 days. In RCC, the highest level was
480 pg/ml on 28(th) day. It was in the normal range in buffy-coat depleted RCC up
to 28 days. RANTES level was significantly low in buffy-coat depleted RCC
compared to RCC. We conclude that WB has high levels of IL-8 and RANTES. The
levels of cytokines are affected by storage period and LR. Comparison of WB and
buffy-coat depleted RCC shows significantly low levels of IL-6, IL-8, and RANTES
in buffy-coat depleted RCC. This study emphasizes the use of red cell components
instead of WB and buffy-coat depleted RCC instead of RCC.
PMID- 26420934
TI - Alloimmunization due to red cell antibodies in Rhesus positive Omani Pregnant
Women: Maternal and Perinatal outcome.
AB - OBJECTIVE: This study is aimed to determine the prevalence of alloimmunization
due to antibodies to red blood cell (RBC) antigens (other than rhesus [Rh]
antigen) and report the maternal, perinatal, and neonatal outcomes. MATERIALS AND
METHODS: A retrospective review of medical records of all patients with minor
RBCs antibodies alloimmunization who were followed and delivered at Sultan Qaboos
University Hospital, Oman from June 2011 to June 2013. Maternal characteristics,
antibody type, antibody titer in addition to perinatal and neonatal outcomes were
reviewed. RESULTS: There were 1160 patients with Rh positive status in the study.
The most common ABO blood group was O, followed by A, B, and AB. We found 33 out
of 1160 Rh positive women alloimmunized with minor RBCs antibodies that gave a
prevalence of minor RBCs alloimmunization of 2.7%. The most frequent antibody was
anti-E 38%, followed by anti-c 17% and anti-kell 17%. 6 of these 33 patients were
identified to have significant antibody titer, and two cases showed evidence of
fetal anemia. Only one case required an intrauterine blood transfusion. The most
common neonatal complication was jaundice in 53%, followed by respiratory
distress syndrome in 28%. Two cases complicated by neonatal anemia required a
postnatal blood transfusion. CONCLUSION: Alloimmunization with anti-E, anti-c,
and anti-kell were the most common antibodies among the study group. Minor RBCs
alloimmunization was an important cause of neonatal morbidity.
PMID- 26420935
TI - Platelet growth factors from allogeneic platelet-rich plasma for clinical
improvement in split-thickness skin graft.
AB - BACKGROUND AND OBJECTIVES: Platelets are a source of numerous growth factors
which facilitate repair and healing. Thus platelet rich plasma has been
increasingly used as a treatment modality in the field of reconstructive
surgeries for wound healing. This preliminary study was carried out to explore
whether platelet growth factors from platelet rich plasma could be used for
enhancement of split thickness skin graft survival. MATERIALS AND METHODS: Twenty
patients (13 males and 7 females) requiring split thickness skin graft for
various clinical reasons were enrolled in the study. Platelet rich plasma was
collected by apheresis and frozen at -80 degrees C. It was thawed at room
temperature immediately before its intended application. PRP was applied only on
one half of the wound, while another half served as control. Patient was followed
for 6 weeks. The effect was assessed at first dressing in terms of graft uptake
and subsequently as time taken for complete healing. RESULTS: There was 100%
uptake of the graft in the area where platelet rich plasma was applied. In the
control area, there was complete graft loss in 4 cases, partial loss in 7 cases
and complete uptake in 9 cases. CONCLUSION: This study demonstrated promising
results on application of PRP to split thickness skin grafts. Further randomized
studies with greater sample size may be undertaken to establish platelet rich
plasma as a validated treatment modality.
PMID- 26420936
TI - Efficacy of platelet-rich plasma in treatment of androgenic alopecia.
AB - BACKGROUND: Platelet-rich plasma (PRP) has shown remarkable beneficial effects
without any major adverse reactions in the treatment of androgenic alopecia. The
growth factors in activated autologous PRP induce the proliferation of dermal
papilla cells. OBJECTIVES: The objective was to investigate the clinical efficacy
of PRP in treatment of androgenic alopecia. MATERIALS AND METHODS: Ten patients
were given autologous PRP injections on the affected area of alopecia over a
period of 3 months at interval of 2-3 weeks and results were assessed. RESULTS:
Three months after the treatment, the patients presented clinical improvement in
the hair counts, hair thickness, hair root strength, and overall alopecia.
CONCLUSION: PRP appears to be a cheap, effective, and promising therapy for
androgenic alopecia with no major adverse effects.
PMID- 26420937
TI - Optimizing cord blood collections: Assessing the role of maternal and neonatal
factors.
AB - BACKGROUND: As processing and cryopreservation of cord blood is time consuming
and costly, it is essential to select units with optimal CD34+ cells, total
nucleated cell (TNC) number and colony forming units (CFUs). These are the most
important factors affecting outcome of UCB transplantation and are influenced by
various maternal and neonatal factors. AIM AND OBJECTIVES: To determine the
maternal and neonatal factors affecting TNC and CD34+ cell counts in cord blood
so as to aid in proper selection of cord blood units for cryopreservation.
MATERIALS AND METHODS: A total of 100 UCB units were collected from normal
vaginal deliveries, processed and assessed for volume, TNC, CD34+ cell count and
CFU-GM. These parameters were then analyzed to find out whether they correlated
with maternal and neonatal characteristics such as mother's age, parity,
gestational age, baby's birth weight, and sex. RESULTS: The volume of CB
collected significantly correlated with the TNC, CD34+ cell, and CFU-GM yields (P
< 0.02). A heavier placenta (P < 0.05), and a heavier baby (P < 0.002) were
associated with a significantly greater volume of CB whereas the age, parity of
mother and the sex of the baby had no significant effect. CONCLUSION: The only
factors found to affect the TNC and CD34+ cell counts significantly were weight
of the baby and placenta and the volume of cord blood collected. Since these
factors are of prognostic significance, their analysis will aid in deciding which
UCB unit should be processed and cryopreserved for UCB banking and subsequent
transplantation.
PMID- 26420938
TI - Tranexamic acid reduces blood loss and need of blood transfusion in total knee
arthroplasty: A prospective, randomized, double-blind study in Indian population.
AB - INTRODUCTION: For quite a few years, tranexamic acid (TEA) has been used during
total knee arthroplasty (TKA) to reduce blood loss. However, no consensus exits
regarding its timing and doses. MATERIALS AND METHODS: We conducted a
prospective, randomized double-blinded study of 56 patients in the Indian
population undergoing TKA from 2011 to 2012. A dose of 10 mg/kg body weight of
TEA (three doses) was given in one group and normal saline was administered in
the other. RESULTS: The mean blood loss in the TEA unilateral group was 295 mL +/
218 mL and in the placebo group was 482 mL +/- 186 mL (P < 0.005). In the
bilateral TEA group, the mean blood loss was 596 mL +/- 235 mL and in the placebo
group was 1349 mL +/- 41 mL (P < 0.005). CONCLUSION: The number of patients
requiring blood transfusion reduced substantially. There was no increase in the
risk of deep vein thrombosis (DVT) and pulmonary embolism. TEA reduces
intraoperative and postoperative blood loss and thus reduces the need of
allogenic blood transfusion.
PMID- 26420939
TI - Clinical and serological characterization of cold agglutinin syndrome in a
Tertiary Care Hospital in Eastern India.
AB - BACKGROUND AND AIM: Cold agglutinin syndrome (CAS) primary or secondary
represents approximately 16-32% of autoimmune hemolytic anemia cases. Most
patients present with mild, chronic hemolytic anemia with exacerbation of the
condition in the cold environment. Red cell transfusions are only indicated when
there is a life-threatening anemia causing crisis. We studied the clinical and
serological characterization of CAS with the aim that the information gained from
this study would help in proper diagnosis and management of these patients.
MATERIALS AND METHODS: The prospective study included nine patients who were
admitted with severe anemia. Detailed work-up were conducted to establish the
diagnosis, severity of in vivo hemolysis and transfusion management. RESULTS: All
patients presented with pallor, weakness, fatigue and painful fingers and toes
with exacerbation of symptoms in winter months. Secondary CAS was observed in
three patients suffering from malignant lymphoma. Red cells of all patients were
coated with complements (C3) more specifically C3d. In one patient suffering from
malignant lymphoma, the cold autoagglutinin titer was as high as 4096.
Autoantibody in seven patients was specific to "I" antigen and one to "i"
antigen. CONCLUSIONS: We conclude that detailed clinical and serological
characterization is needed to diagnose and manage CAS. Whereas avoidance of cold
exposure is the primary therapy, but no critical patient should be denied blood
transfusion due to serological complications. All transfusion services should
follow the correct protocol to maximize blood safety in CAS.
PMID- 26420940
TI - Dengue viremia in blood donors in Northern India: Challenges of emerging dengue
outbreaks to blood transfusion safety.
AB - BACKDROUND: Emerging infectious diseases pose threats to the general human
population; including recipients of blood transfusions. Dengue is spreading
rapidly to new areas and with increasing frequency of major outbreaks. Screening
blood for dengue antigens in dengue-endemic countries would be costly and should,
therefore, be recommended only after careful assessment of risk for infection and
cost. AIM: A prospective study was conducted to establish the magnitude of the
threat that dengue poses to blood safety where it is sporadic with seasonal
variations, to quantify risk and to assess that whether screening is feasible and
cost-effective. MATERIALS AND METHODS: Nonstructural protein 1 (NS1) antigen test
was done on 1709 donations during dengue outbreak in the months August to
November 2013 as an additional test using Bio-Rad Platelia Dengue NS1AG test kit
which is one step sandwich format microplate enzyme immunoassay using murine
monoclonal antibodies for capture and revelation. Chi-square test was used to
find statistical significance. RESULTS AND CONCLUSIONS: Majority cases were whole
blood, replacement, male donors with 76.10% donors in <35 years age group. About
17.85% were single donor platelet donations. NS1 antigen in all donors was
negative. In the past, dengue affected mainly children who do not donate blood.
With the changing trend, mean age of infection increased affecting the population
that does donate blood, further reducing blood donation pool. Further studies
need to be done in different geographic regions of the country during dengue
transmission season to establish maximum incidence of viremic donations, rates of
transfusion transmission and clinical consequences in recipients. If risk is
found to be substantial, decision will be taken by the policymakers at what
threshold screening should be instituted to ensure safe blood transfusion.
PMID- 26420941
TI - Clinico-serologic co-relation in bi-directional ABO incompatible hemopoietic stem
cell transplantation.
AB - BACKGROUND: The ABO blood group system is of prime significance in red cell
transfusion and organ transplantation. However, ABO compatibility is not critical
in allogenic hemopoietic stem cell transplantation (HSCT) and approximately 40
50% of hemopoietic stem cell transplants are ABO incompatible. This
incompatibility may be major, minor or bi-directional. Though there are
descriptions of transfusion practice and protocols in ABO incompatible HSCT,
there are considerable variations and transfusion support in these patients can
be very challenging. AIMS: The immunohematologic observations in two cases of bi
directional ABO incompatible HSCT have been described, and clinico-serologic
correlation has been attempted. MATERIALS AND METHODS: In both cases, peripheral
blood stem cell harvests were obtained using the Cobe spectra cell separator.
Immunohematologic assessments in the donor and recipient were done as a part of
pre HSCT evaluation. Both the standard tube technique and column agglutination
method (Ortho Biovue Micro Bead System) was used. Antibody screen was done by
column agglutination method using three cell panel (Surgiscreen cells).
Isoagglutinin titration was done by the master dilution method and standard
validated techniques were used. RESULTS: The pattern of laboratory findings in
the two cases was different and so were the clinical outcomes. Although there was
early engraftment in the first case, the second case developed pure red cell
aplasia and this was well-reflected in the immunohematologic assessments.
CONCLUSION: Immunohematologic assessment correlated well with the clinical
picture and could be used to predict clinical outcome and onset of complications
in ABO incompatible HSCT.
PMID- 26420942
TI - Establishing a sample-to cut-off ratio for lab-diagnosis of hepatitis C virus in
Indian context.
AB - INTRODUCTION: Lab-diagnosis of hepatitis C virus (HCV) is based on detecting
specific antibodies by enzyme immuno-assay (EIA) or chemiluminescence immuno
assay (CIA). Center for Disease Control reported that signal-to-cut-off (s/co)
ratios in anti-HCV antibody tests like EIA/CIA can be used to predict the
probable result of supplemental test; above a certain s/co value it is most
likely to be true-HCV positive result and below that certain s/co it is most
likely to be false-positive result. A prospective study was undertaken in
patients in tertiary care setting for establishing this "certain" s/co value.
MATERIALS AND METHODS: The study was carried out in consecutive patients
requiring HCV testing for screening/diagnosis and medical management. These
samples were tested for anti-HCV on CIA (VITROS((r)) Anti-HCV assay, Ortho
Clinical Diagnostics, New Jersey) for calculating s/co value. The supplemental
nucleic acid test used was polymerase chain reaction (PCR) (Abbott). PCR test
results were used to define true negatives, false negatives, true positives, and
false positives. Performance of different putative s/co ratios versus PCR was
measured using sensitivity, specificity, positive predictive value and negative
predictive value and most appropriate s/co was considered on basis of highest
specificity at sensitivity of at least 95%. RESULTS: An s/co ratio of >=6 worked
out to be over 95% sensitive and almost 92% specific in 438 consecutive patient
samples tested. CONCLUSION: The s/co ratio of six can be used for lab-diagnosis
of HCV infection; those with s/co higher than six can be diagnosed to have HCV
infection without any need for supplemental assays.
PMID- 26420943
TI - A comprehensive serological and supplemental evaluation of hepatitis B
"seroyield" blood donors: A cross-sectional study from a tertiary healthcare
center in India.
AB - BACKGROUND: The present study addressed the interesting findings of supplemental
evaluation of hepatitis B "seroyield" donors. MATERIALS AND METHODS: Each blood
donor sample was tested for anti-human immunodeficiency virus type I (HIV-I)/HIV
type II (HIV-II), HBsAg, and anti-hepatitis C virus (HCV) antibody by enhanced
chemiluminescence method and subjected to individual donor-nucleic acid testing
(NAT) for HIV-I, hepatitis B virus (HBV), and HCV. NAT test was performed using
the eSAS system, Procleix Ultrio Assay, Novartis Diagnostics, CA, US.
Confirmation of HBsAg was done using HBsAg Confirmatory Kit (Ortho Clinical
Diagnostics, Johnson & Johnson, USA) and viral load assessment was done using
Cobas TaqMan real time-polymerase chain reaction (RT-PCR) assay (Roche Molecular
Systems, Branchburg, NJ, USA). To provide information on the stage of infection,
specimens were tested for anti-HBc total (IgG + IgM), anti-HBc IgM and HBeAg.
HBeAg-negative samples were tested for anti-HBe antibody. RESULTS: A total of 60
hepatitis B seroyield donors which showed mean initial sample/cutoff of 1.6 with
enhanced chemiluminescence assay were investigated further for confirmation of
disease status. All 60 cases were confirmed positive with neutralization assay
(VITROS HBsAg Confirmatory Kit) while no target was detected on viral load
assessment with RT-PCR. Sixteen donors were HBeAg positive (4 IgM anti-HBc
positive and 12 IgM anti-HBc negative) and 44 were IgM anti-HBc negative, anti
HBc total positive, and anti-HBe positive. CONCLUSION: About 7.7% of HBsAg
positive and NAT nonreactive donors (nondetectable HBV DNA) could be potentially
infectious (HBeAg positive), whereas rest of the donors were consistent with
chronic HBV infection.
PMID- 26420944
TI - Evaluation of the pneumatic tube system for transportation of packed red cell
units.
AB - BACKGROUND: Pneumatic tube system (PTS) is commonly used in hospital settings to
transport blood samples to diagnostic laboratories. At our blood center, we
receive blood requisitions via the PTS, but units are carried to the ward by
human courier. Recently we considered using the PTS for transporting blood units.
Since, there are reports of hemolysis in blood samples sent through the PTS, we
evaluated this system for transporting red cell units. AIMS: The aim was to
assess the effect of PTS transport on the quality of packed red cell units.
MATERIALS AND METHODS: A total of 50 red blood cells units (RBC), (25 non
irradiated and 25 irradiated) were subjected to transportation through the PTS.
The control arm in the study was age-matched RBC units not subjected to PTS
transport. Each RBC unit was evaluated for hemoglobin (Hb), lactate
dehydrogenase, potassium and plasma hemoglobin (Hb). The paired t-test was used
to compare these parameters, and the P value was calculated. RESULTS AND
CONCLUSION: The percentage of hemolysis after transportation through PTS was
below the recommended guidelines. Delivery of the blood unit to the wrong
station, bags lying unattended at the destination were few of the problems that
had to be addressed. To conclude, though the PTS is a safe means of transporting
blood products with reduction in the turn-around-time, it must be validated
before use.
PMID- 26420945
TI - Individual donor-nucleic acid testing for human immunodeficiency virus-1,
hepatitis C virus and hepatitis B virus and its role in blood safety.
AB - BACKGROUND: Transfusion-transmitted infections (TTIs) are one of the biggest
threats to blood transfusion safety. Nucleic acid testing (NAT) in blood donor
screening has been implemented in many countries to reduce the risk of TTIs. NAT
shortens this window period, thereby offering blood centers a much higher
sensitivity for detecting viral infections. AIMS: The objective was to assess the
role of individual donor-NAT (ID-NAT) for human immunodeficiency virus-1 (HIV-1),
hepatitis C virus (HCV) and hepatitis B virus (HBV) and its role in blood safety.
MATERIALS AND METHODS: A total of 32978 donations were tested for all three
viruses using enzyme-linked immuno-sorbent assay (Vironostika((r)) HIV Ag-Ab,
Hepanostika((r)) HCV ultra and hepatitis B surface antigen ultra by Biomerieux)
and ID-NAT using Procleix Ultrio plus((r)) Assay (Novartis Diagnostic, USA). All
initial NAT reactive samples and serology nonreactive were retested in triplicate
and NAT discriminatory assay for HIV-1, HCV and HBV were performed. RESULTS: Of
the 32978 samples, 43 (0.13%) were found to be ID-NAT reactive but seronegative.
Out of 43, one for HIV-1, 13 for HCV and 27 for HBV were reactive by
discriminatory assays. There were two samples that were reactive for both HCV-HBV
and counted as HCV-HBV co-infection NAT yield. The prevalence of these viruses in
our sample, tested by ID-NAT is 0.06%, 0.71%, and 0.63% for HIV-1, HCV and HBV
respectively. The combined NAT yield among blood donors was 1 in 753. CONCLUSION:
ID-NAT testing for HIV-1, HCV and HBV can tremendously improve the efficacy of
screening for protecting blood recipient from TTIs. It enables detection of these
viruses that were undetected by serological test and thus helped in providing
safe blood to the patients.
PMID- 26420946
TI - Seroepidemiology of human T-cell lymphotropic virus type-I in blood donors of
Northeastern Iran, Sabzevar.
AB - BACKGROUND AND OBJECTIVES: Human T-cell lymphotropic virus type-I (HTLV-I)
infection is considered as a public health challenge in endemic areas. The virus
is associated with severe diseases, such as adult T-cell leukemia/lymphoma, and
HTLV-I-associated myelopathy/tropical spastic paraparesis. One of the major
routes of the HTLV-I transmission includes blood transfusion. Sabzevar is located
in the endemic region of HTLV-I infection. The aim of the present study was to
determine the seroprevalence of HTLV-I infection in the blood donors in Sabzevar.
MATERIALS AND METHODS: A total of 35,067 blood donors in Sabzevar from March 2009
to April 2012 who were screened with HTLV-I on the enzyme-linked immunosorbent
assay screening test were included in this survey. Reactive samples that
confirmed by western blot were considered to be seropositive cases. The required
data were obtained from blood donors' database of blood transfusion service.
RESULTS: The overall prevalence of HTLV-1 based on the positive result of western
blot test was 0.14%. The seropositive donors aged 17-59 years with a mean age of
38.10 +/- 11.82. The prevalence rates of HTLV-I infection in 3 years of study
were 0.19%, 0.14%, and 0.09%, respectively. A significant relation between age,
sex, educational level, and history of blood donation was observed with
seropositivity of HTLV-I. CONCLUSION: The improvement of donor selection and
laboratory screening caused a decline in the prevalence of infection in blood
donors. Given the lower prevalence of infection in regular donors with lower age
and higher educational level, more efforts should be done to attract blood donors
from these populations.
PMID- 26420947
TI - Successful use of the cell separator hemonetics multicomponent collection system+
for therapeutic thrombocytapheresis in a low body weight child of essential
thrombocythemia.
AB - In children, essential thrombocythemia (ET) is extremely rare with an incidence
of 1/million. Since thromboembolic complications are more common than hemorrhagic
manifestation, immediate thromboctyapheresis by an automated cell separator can
prevent untoward consequences in the form of cerebrovascular, coronary or
peripheral vascular occlusive events. Due to varied options of automated cell
separators, selecting an appropriate cell separator in such acute emergency
situation can be confusing for a treating physician, especially if the patient is
a child of low body weight. We present here the successful use of hemonetics
multicomponent collection system (MCS+) for therapeutic platelet reduction (TPR)
in a 12-year-old male child of 28 kg with extreme thrombocytosis (TS) (3072 *
10(9)/l) due to ET. A total of three procedures were performed without priming of
the machine with allogenic blood. We observed hemonetics MCS+, best suited for
TPR even in children with low body weight.
PMID- 26420948
TI - Anti-G antibody in alloimmunized pregnant women: Report of two cases.
AB - Anti-G has been reported as a possible cause of hemolytic disease of the fetus
and newborn (HDFN), either independently or in association with anti-D, anti-C or
both. The antibody mimics the pattern of anti-C and anti-D reactivity in the
identification panel and is often present along with either or both of these
antibodies. The differentiation of anti-D, -C and-G in routine pretransfusion
workup is particularly essential in antenatal cases. We report two antenatal
cases where anti-G was identified on advanced immunohematological workup, in
addition to other alloantibodies.
PMID- 26420949
TI - An acute hemolytic transfusion reaction due to the "anti-c" rhesus antibody: A
case report emphasizing the role of transfusion medicine.
AB - Rhesus (Rh) mediated hemolytic transfusion reactions (HTR) are usually
immunoglobulin G mediated and delayed onset. Rh antibodies being the cause of
acute HTR (AHTR) and intravascular hemolysis are still under debate. We report
here a case of a 53-year-old male who developed AHTR due to "anti-c" antibodies
within 3 h of blood transfusion, precipitating fatal acute liver failure in a
patient with hepatitis C related chronic liver disease. This case emphasizes the
need of inclusion of antibody screening in routine pretransfusion testing as well
as a critical role of transfusion medicine specialists for early diagnosis and
minimizing transfusion-related morbidity and mortality.
PMID- 26420950
TI - An incident of incorrect blood component transfusion: The need for constant
hemovigilance.
PMID- 26420951
TI - CAPA analysis of clotted red cell unit detected during leukodepletion process:
Importance of quality check on blood collection monitors.
PMID- 26420952
TI - Evidence for an influence of secretor status on levels of the ABO-isoantibodies
in serum.
PMID- 26420953
TI - Mesenchymal stem cell therapy for cirrhosis: Present and future perspectives.
AB - Cirrhosis occurs as a result of various chronic liver injuries, which may be
caused by viral infections, alcohol abuse and the administration of drugs and
chemicals. Recently, bone marrow cells (BMCs), hematopoietic stem cells (HSCs)
and mesenchymal stem cells (MSCs) have been used for developing treatments for
cirrhosis. Clinical trials have investigated the therapeutic potential of BMCs,
HSCs and MSCs for the treatment of cirrhosis based on their potential to
differentiate into hepatocytes. Although the therapeutic mechanisms of BMC, HSC
and MSC treatments are still not fully characterized, the evidence thus far has
indicated that the potential therapeutic mechanisms of MSCs are clearer than
those of BMCs or HSCs with respect to liver regenerative medicine. MSCs suppress
inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte
regeneration, reverse liver fibrosis and enhance liver functionality. This paper
summarizes the clinical studies that have used BMCs, HSCs and MSCs in patients
with liver failure or cirrhosis. We also present the potential therapeutic
mechanisms of BMCs, HSCs and MSCs for the improvement of liver function.
PMID- 26420954
TI - Molecular prognostic prediction in liver cirrhosis.
AB - The natural history of cirrhosis varies and therefore prognostic prediction is
critical given the sizable patient population. A variety of clinical prognostic
indicators have been developed and enable patient risk stratification although
their performance is somewhat limited especially within relatively earlier stage
of disease. Molecular prognostic indicators are expected to refine the
prediction, and potentially link a subset of patients with molecular targeted
interventions that counteract poor prognosis. Here we overview clinical and
molecular prognostic indicators in the literature, and discuss critical issues to
successfully define, evaluate, and deploy prognostic indicators as clinical
scores or tests. The use of liver biopsy has been diminishing due to sampling
variability on fibrosis assessment and emergence of imaging- or lab test-based
fibrosis assessment methods. However, recent rapid developments of genomics
technologies and selective molecular targeted agents has highlighted the need for
biopsy tissue specimen to explore and establish molecular information-guided
personalized/stratified clinical care, and eventually achieve "precision
medicine".
PMID- 26420956
TI - Change of strategies and future perspectives against hepatitis B virus recurrence
after liver transplantation.
AB - A few decades ago, liver transplantation in patients with chronic hepatitis B
virus (HBV) infection was considered a relative contraindication because of the
high rate of graft infections and poor prognosis. Since then, remarkable progress
was introduced by using nucleos(t)ide analogues and/or hepatitis B immunoglobulin
(HBIg) and liver transplantation for HBV-related disease is now becoming one of
the good indication. However, high cost burden is the main problem for this
combination prophylaxis for a long time use, and this issue should be emerged to
be resolved. In this review, we show the progress of post anti-HBV strategies
showing the history from introduction of HBIg and nucleos(t)ide analogues to
recent new strategies with hepatitis B vaccine or saving or stopping protocols of
HBIg, and clarify and discuss how to do for further improvement of prevention
strategies with better quality.
PMID- 26420955
TI - Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and
prophylaxis recommendations.
AB - Accompanying the increased use of biological and non-biological antirheumatic
drugs, a greater number of cases of hepatitis B virus (HBV) reactivation have
been reported in inactive hepatitis B surface antigen (HBsAg) carriers and also
in HBsAg-negative patients who have resolved HBV infection. The prevalence of
resolved infection varies in rheumatic disease patients, ranging from 7.3% to
66%. Through an electronic search of the PubMed database, we found that among 712
patients with resolved infection in 17 observational cohort studies, 12
experienced HBV reactivation (1.7%) during biological antirheumatic therapy.
Reactivation rates were 2.4% for etanercept therapy, 0.6% for adalimumab, 0% for
infliximab, 8.6% for tocilizumab, and 3.3% for rituximab. Regarding non
biological antirheumatic drugs, HBV reactivation was observed in 10 out of 327
patients with resolved infection from five cohort studies (3.2%). Most of these
patients received steroids concomitantly. Outcomes were favorable in rheumatic
disease patients. A number of recommendations have been established, but most of
the supporting evidence was derived from the oncology and transplantation fields.
Compared with patients in these fields, rheumatic disease patients continue
treatment with multiple immunosuppressants for longer periods. Optimal frequency
and duration of HBV-DNA monitoring and reliable markers for discontinuation of
nucleoside analogues should be clarified for rheumatic disease patients with
resolved HBV infection.
PMID- 26420957
TI - Chronic hepatitis C virus infection and lipoprotein metabolism.
AB - Hepatitis C virus (HCV) is a hepatotrophic virus and a major cause of chronic
liver disease, including hepatocellular carcinoma, worldwide. The life cycle of
HCV is closely associated with the metabolism of lipids and lipoproteins. The
main function of lipoproteins is transporting lipids throughout the body.
Triglycerides, free cholesterol, cholesteryl esters, and phospholipids are the
major components of the transported lipids. The pathway of HCV assembly and
secretion is closely linked to lipoprotein production and secretion, and the
infectivity of HCV particles largely depends on the interaction of lipoproteins.
Moreover, HCV entry into hepatocytes is strongly influenced by lipoproteins. The
key lipoprotein molecules mediating these interactions are apolipoproteins.
Apolipoproteins are amphipathic proteins on the surface of a lipoprotein
particle, which help stabilize lipoprotein structure. They perform a key role in
lipoprotein metabolism by serving as receptor ligands, enzyme co-factors, and
lipid transport carriers. Understanding the association between the life cycle of
HCV and lipoprotein metabolism is important because each step of the life cycle
of HCV that is associated with lipoprotein metabolism is a potential target for
anti-HCV therapy. In this article, we first concisely review the nature of
lipoprotein and its metabolism to better understand the complicated interaction
of HCV with lipoprotein. Then, we review the outline of the processes of HCV
assembly, secretion, and entry into hepatocytes, focusing on the association with
lipoproteins. Finally, we discuss the clinical aspects of disturbed
lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in
chronic HCV infection with regard to abnormal apolipoproteins.
PMID- 26420958
TI - Potentiality of immunotherapy against hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is
the fifth most common cancer worldwide and the second leading cause of cancer
related death. Despite the high incidence, treatment options remain limited for
advanced HCC, and as a result prognosis continues to be poor. Current therapeutic
options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New
treatment modalities to prolong survival and to minimize the risk of adverse
response are desperately needed for patients with advanced HCC. Tumor
immunotherapy is a promising, novel treatment strategy that may lead to
improvements in both treatment-associated toxicity and outcome. The strategies
have developed in part through genomic studies that have yielded candidate target
molecules and in part through basic biology studies that have defined the
pathways and cell types regulating immune response. Here, we summarize the
various types of HCC immunotherapy and argue that the new-found field of HCC
immunotherapy might provide critical advantages in the effort to improve
prognosis of patients with advanced HCC. Already several immunotherapies, such as
tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer
immunotherapy, have demonstrated safety and feasibility in HCC patients.
Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC
patients; overcoming this challenge will place immunotherapy at the forefront of
HCC treatment, possibly in the near future.
PMID- 26420959
TI - Transarterial chemoembolization in hepatocellular carcinoma treatment: Barcelona
clinic liver cancer staging system.
AB - Hepatocellular carcinoma (HCC), the fifth most common cancer that predominantly
occurs in liver cirrhosis patients, requires staging systems to design
treatments. The barcelona clinic liver cancer staging system (BCLC) is the most
commonly used HCC management guideline. For BCLC stage B (intermediate HCC),
transarterial chemoembolization (TACE) is the standard treatment. Many studies
support the use of TACE in early and advanced HCC patients. For BCLC stage 0
(very early HCC), TACE could be an alternative for patients unsuitable for
radiofrequency ablation (RFA) or hepatic resection. In patients with BCLC stage
A, TACE plus RFA provides better local tumor control than RFA alone. TACE can
serve as bridge therapy for patients awaiting liver transplantation. For patients
with BCLC B, TACE provides survival benefits compared with supportive care
options. However, because of the substantial heterogeneity in the patient
population with this stage, a better patient stratification system is needed to
select the best candidates for TACE. Sorafenib represents the first line
treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a
demonstrable effect in delaying tumor progression. Additionally, TACE plus
radiotherapy has yielded better survival in patients with HCC and portal venous
thrombosis. Considering these observations together, TACE clearly has a critical
role in the treatment of HCC as a stand-alone or combination therapy in each
stage of HCC. Diverse treatment modalities should be used for patients with HCC
and a better patient stratification system should be developed to select the best
candidates for TACE.
PMID- 26420960
TI - Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma:
Are we getting there?
AB - Sorafenib is the current standard treatment for advanced hepatocellular carcinoma
(HCC), but its efficacy is modest with low response rates and short response
duration. Predictive biomarkers for sorafenib efficacy are necessary. However,
efforts to determine biomarkers for sorafenib have led only to potential
candidates rather than clinically useful predictors. Studies based on patient
cohorts identified the potential of blood levels of angiopoietin-2, hepatocyte
growth factor, insulin-like growth factor-1, and transforming growth factor-beta1
for predicting sorafenib efficacy. Alpha-fetoprotein response, dynamic contrast
enhanced magnetic resonance imaging, and treatment-related side effects may serve
as early surrogate markers. Novel approaches based on super-responders or
experimental mouse models may provide new directions in biomarker research. These
studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression
of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await
validation. A group effort that considers various prognostic factors and proper
collection of tumor tissues before treatment is imperative for the success of
future biomarker research in advanced HCC.
PMID- 26420961
TI - Laparoscopic sleeve gastrectomy and gastroesophageal reflux.
AB - Bariatric surgery is the only effective procedure that provides long-term
sustained weight loss. Sleeve gastrectomy (SG) has emerged over the last few
years to be an ideal bariatric procedure because it has several advantages
compared to more complex bariatric procedures, including avoiding an intestinal
bypass. However, several published follow-up studies report an increased rate of
gastroesophageal reflux (GERD) after a SG. GERD is described as either de novo or
as being caused by aggravation of preexisting symptoms. However, the literature
on this topic is ambivalent despite the potentially increased rate of GERDs that
may occur after this common bariatric procedure. This article reviews the
mechanisms responsible for GERD in obese subjects as well as the results after a
SG with respect to GERD. Future directions for clinical research are discussed
along with the current surgical options for morbidly obese patients with GERD and
undergoing bariatric surgery.
PMID- 26420962
TI - TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for
inflammatory bowel disease development.
AB - AIM: To investigate the association between tumor protein 53 (TP53) codon 72
polymorphisms and the risk for inflammatory bowel disease (IBD) development.
METHODS: Numerous genetic and epigenetic drivers have been identified for IBD
including the TP53 gene. Pathogenic mutations in TP53 gene have only been
reported in 50% of colorectal cancer (CRC) patients. A single nucleotide
polymorphism (SNP) in the TP53 gene resulting in the presence of either arginine
(Arg) or proline (Pro) or both at codon 72 was shown to alter TP53 tumor
suppressor properties. This SNP has been investigated as a risk factor for
numerous cancers, including CRC. In this study we analyzed TP53 codon 72
polymorphism distribution in 461 IBD, 181 primary sclerosing cholangitis patients
and 62 healthy controls. Genotyping of TP53 was performed by sequencing and
restriction fragment length polymorphism analysis of genomic DNA extracted from
peripheral blood. RESULTS: The most frequent TP53 genotype in IBD patients was
Arg/Arg occurring in 54%-64% of cases (and in only 32% of controls). Arg/Pro was
the most prevalent genotype in controls (53%) and less common in patients (31%
40%). Pro/Pro frequency was not significantly different between controls and IBD
patients. CONCLUSION: The data suggests that the TP53 codon 72 Arg/Arg genotype
is associated with increased risk for IBD development.
PMID- 26420963
TI - Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in
mice.
AB - AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a
chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC).
METHODS: BALB/c nude mice were randomized into four groups 24 h before
subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate
buffered saline (PBS) into the right flank. The control group (n = 10) was fed a
standard diet while treatment groups (n = 10 each) were fed a standard daily diet
supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day)
for 21 d. Tumor growth was measured once each week, and tumor volume (V) was
calculated with the following equation: V = (L * W(2)) * 0.52, where L is the
length and W is the width of the xenograft. After 21 d, mice were killed under
ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated
through detection of DNA fragmentation with gel electrophoresis and the terminal
deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)
assay. Western blot analysis was performed to determine the expression of
apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved
caspase-3. RESULTS: UDCA suppressed tumor growth relative to controls. The mean
tumor volumes were the following: control, 1090 +/- 89 mm(3); 30 mg/kg per day,
612 +/- 46 mm(3); 50 mg/kg per day, 563 +/- 38 mm(3); and 70 mg/kg per day, 221
+/- 26 mm(3). Decreased tumor volumes reached statistical significance relative
to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70
mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA
fragmentation observed on gel electrophoresis and in the TUNEL assay (control,
1.6% +/- 0.3%; 30 mg/kg per day, 2.9% +/- 0.5%; 50 mg/kg per day, 3.15% +/- 0.7%,
and 70 mg/kg per day, 4.86% +/- 0.9%). Western blot analysis revealed increased
expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which
induce apoptosis, but decreased expression of BCL2 protein, which is an inhibitor
of apoptosis, following administration of UDCA. CONCLUSION: UDCA suppresses
growth of BEL7402 hepatocellular carcinoma cells in vivo, in part through
apoptosis induction, and is thus a candidate for therapeutic treatment of HCC.
PMID- 26420964
TI - Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury
in mice.
AB - AIM: To investigate the effects of Recql5 deficiency on liver injury induced by
lipopolysaccharide/D-galactosamine (LPS/D-Gal). METHODS: Liver injury was induced
in wild type (WT) or Recql5-deficient mice using LPS/D-Gal, and assessed by
histological, serum transaminases, and mortality analyses. Hepatocellular
apoptosis was quantified by transferase dUTP nick end labeling assay and Western
blot analysis of cleaved caspase-3. Liver inflammatory chemokine and cytochrome
P450 expression was analyzed by quantitative reverse transcription-PCR.
Neutrophil infiltration was evaluated by myeloperoxidase activity. Expression and
phosphorylation of ERK, JNK, p65, and H2A.X was determined by Western blot.
Oxidative stress was evaluated by measuring malondialdehyde production and nitric
oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and
glutathione reductase activity. RESULTS: Following LPS/D-Gal exposure, Recql5
deficient mice exhibited enhanced liver injury, as evidenced by more severe
hepatic hemorrhage, higher serum aspartate transaminase and alanine transaminase
levels, and lower survival rate. As compared to WT mice, Recql5-deficient mice
showed an increased number of apoptotic hepatocytes and higher cleaved caspase-3
levels. Recql5-deficient mice exhibited increased DNA damage, as evidenced by
increased gamma-H2A.X levels. Inflammatory cytokine levels, neutrophil
infiltration, and ERK phosphorylation were also significantly increased in the
knockout mice. Additionally, Recql5-deficient mice exhibited increased
malondialdehyde production and elevated inducible nitric oxide synthase,
superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase
activity, indicative of enhanced oxidative stress. Moreover, CYP450 expression
was significantly downregulated in Recql5-deficient mice after LPS/D-Gal
treatment. CONCLUSION: Recql5 protects the liver against LPS/D-Gal-induced injury
through suppression of hepatocyte apoptosis and oxidative stress and modulation
of CYP450 expression.
PMID- 26420966
TI - Liver resection for hepatocellular carcinoma using a microwave tissue coagulator:
Experience of 1118 cases.
AB - AIM: To present our extensive experience of hepatectomy for hepatocellular
carcinoma using a microwave tissue coagulator to demonstrate the effectiveness of
this device. METHODS: A total of 1118 cases (1990-2013) were reviewed, with an
emphasis on intraoperative blood loss, postoperative bile leakage and
fluid/abscess formation, and adaptability to anatomical resection and hepatectomy
with hilar dissection. RESULTS: The median intraoperative blood loss was 250 mL;
postoperative bile leakage and fluid/abscess formation were seen in 3.0% and 3.3%
of cases, respectively. Anatomical resection was performed in 275 cases,
including 103 cases of hilar dissection that required application of microwave
coagulation near the hepatic hilum. There was no clinically relevant biliary
tract stricture or any vascular problems due to heat injury. Regarding the
influence of cirrhosis on intraoperative blood loss, no significant difference
was seen between cirrhotic and non-cirrhotic patients (P = 0.38), although
cirrhotic patients tended to have smaller tumors and underwent less invasive
operations. CONCLUSION: This study demonstrated outcomes of an extensive
experience of hepatectomy using heat coagulative necrosis by microwave tissue
coagulator.
PMID- 26420965
TI - Equol inhibits proliferation of human gastric carcinoma cells via modulating Akt
pathway.
AB - AIM: To investigate the anti-tumor effects of equol in gastric cancer cells and
the underlying molecular mechanisms. METHODS: MGC-803 cells were employed for in
vitro experiments in this study. Cells were treated with control (vehicle, 0.1%
DMSO) or equol under specified dose titration or time courses. Cell viability was
examined by MTS assay, and the levels of Ki67 were determined by qPCR and
immunofluorescent assay. Changes in cell cycle distribution and apoptosis rate
were detected by flow cytometry. The mRNA expression of cyclin E1 and P21(WAF1)
was determined by qPCR. The protein levels of cell cycle regulators, PARP and
Caspase-3 cleavage, and the phosphorylation of Akt were examined by Western blot.
In addition, to characterize the role of elevated Akt activation in the anti
tumor effect exerted by equol, Ly294002, a PI3K/AKT pathway inhibitor, was used
to pretreat MGC-803 cells. RESULTS: Equol (5, 10, 20, 40, or 80 MUmol/L)
inhibited viability of MGC-803 cells in a dose- and time-dependent manner after
treatment for 24, 36, or 48 h (P < 0.05 for all). Equol also decreased the mRNA
(P < 0.05 for 12 and 24 h treatment) and protein levels of Ki67. Equol treatment
significantly induced G0/G1 cell cycle arrest (P < 0.05), with the percentages of
G0/G1 cells of 32.23% +/- 3.62%, 36.31% +/- 0.24%, 45.58% +/- 2.29%, and 65.10%
+/- 2.04% for equol (0, 10, 20, or 30 MUmol/L) treatment, respectively,
accompanied by a significant decrease of CDK2/4 (P < 0.05 for 24 and 48 h
treatment) and Cyclin D1/Cyclin E1 (P < 0.05), and an increased level of
P21(WAF1) (P < 0.05). A marked increase of apoptosis was observed, with the
percentages of apoptotic cells of 5.01% +/- 0.91%, 14.57% +/- 0.99%, 37.40% +/-
0.58%, and 38.46% +/- 2.01% for equol (0, 5, 10, or 20 MUmol/L) treatment,
respectively, accompanied by increased levels of cleaved PARP and caspase-3. In
addition, we found that equol treatment increased P-Akt (Ser473 and Thr308) at 12
and 24 h compared to vehicle-treated control; longer treatment for 48 h decreased
P-Akt (Ser473 and Thr308). P-Akt at Thr450, however, was decreased by equol
treatment at all time points examined (P < 0.05 for all). Moreover, Akt
inhibition by Ly294002 could not prevent but led to enhanced G0/G1 arrest and
apoptosis. CONCLUSION: Equol inhibits MGC-803 cells proliferation by induction of
G0/G1 arrest and apoptosis. Its anti-cancer effects are likely mediated by
dephosphorylation of Akt at Thr450.
PMID- 26420967
TI - Pathogen profile and drug resistance analysis of spontaneous peritonitis in
cirrhotic patients.
AB - AIM: To investigate the microbiological characteristics and drug resistance in
liver cirrhosis patients with spontaneous peritonitis. METHODS: We analyzed the
data of patients with liver cirrhosis and abdominal infection at the First
Affiliated Hospital of Zhejiang University between January 2011 and December
2013. Pathogens present in the ascites were identified, and their sensitivity to
various antibiotics was determined. RESULTS: We isolated 306 pathogenic bacteria
from 288 cases: In 178 cases, the infection was caused by gram-negative strains
(58.2%); in 85 cases, gram-positive strains (27.8%); in 9 cases, fungi (2.9%);
and in 16 cases, more than one pathogen. The main pathogens were Escherichia coli
(E. coli) (24.2%), Klebsiella pneumoniae (18.9%), Enterococcus spp. (11.1%), and
Staphylococcus aureus (7.5%). Of the 306 isolated pathogens, 99 caused nosocomial
infections and 207 caused community-acquired and other infections. The E. coli
and K. pneumoniae strains produced more extended-spectrum beta-lactamases in
cases of nosocomial infections than non-nosocomial infections (62.5% vs 38%, P <
0.013; 36.8% vs 12.8%, P < 0.034, respectively). The sensitivity to individual
antibiotics differed between nosocomial and non-nosocomial infections:
Piperacillin/tazobactam was significantly more effective against non-nosocomial
E. coli infections (4% vs 20.8%, P < 0.021). Nitrofurantoin had stronger
antibacterial activity against Enterococcus species causing non-nosocomial
infections (36.4% vs 86.3%, P < 0.009). CONCLUSION: The majority of pathogens
that cause abdominal infection in patients with liver cirrhosis are gram
negative, and drug resistance is significantly higher in nosocomial infections
than in non-nosocomial infections.
PMID- 26420968
TI - Predictive value of quantitative contrast-enhanced ultrasound in hepatocellular
carcinoma recurrence after ablation.
AB - AIM: To investigate the relationship between contrast-enhanced ultrasound (CEUS),
basic fibroblast growth factor (bFGF), endothelin-1 (ET-1), and hepatocellular
carcinoma (HCC) recurrence after ablation. METHODS: A total of 51 HCC patients
(38 males and 13 females) who received radiofrequency ablation in our hospital
from June 2012 to July 2014 were enrolled in this study. The patients were
divided into two groups: recurrence group and non-recurrence group. Routine
abdominal examination was first performed in the horizontal position. Then the
patients underwent CEUS and immunohistochemical staining before receiving
radiofrequency ablation. All patients were followed-up every three months for one
year. The results of CEUS and serum tumor marker levels were evaluated and
combined together to estimate HCC recurrence and metastasis. Patients were
divided into two groups: recurrence group and non-recurrence group. Quantitative
parameters of CEUS and tumor expression levels of bFGF and ET-1 were compared
between the two groups, respectively. Binary logistic regression analysis was
used to analyze the relationship between CEUS quantitative parameters, expression
levels of ET-1 and bFGF, and HCC recurrence after ablation. RESULTS: Based on the
quantitative parameters of CEUS before patients received radiofrequency ablation,
the levels of tumor rise time (tRT), tumor time to peak (tTTP), tumor peak
intensity (tPI) and tumor-parenchymal peak intensity (t-pPI) in the recurrence
group were significantly lower than those in the non-recurrence group (16.6 +/-
6.1 vs 23.2 +/- 7.0, P = 0.000; 41.2 +/- 10.2 vs 59.6 +/- 14.2, P = 0.000; 23.8
+/- 6.7 vs 31.4 +/- 6.4, P = 0.000; 7.1 +/- 3.4 vs 14.6 +/- 7.4, P = 0.000;
respectively). The expression levels of bFGF in the recurrence group were
significantly higher than those in the non-recurrence group (P < 0.05). Levels of
tTTP showed a significant inverse correlation with the level of bFGF in tumors (r
= -0.312, P = 0.037). The Binary logistic regression analysis results revealed
that the levels of tRT, tTTP, tPI and the level of bFGF were associated with HCC
recurrence after radiofrequency ablation (P < 0.05). CONCLUSION: CEUS is a
noninvasive and effective method for evaluating the angiogenesis of HCC, and
predicting its recurrence and prognosis.
PMID- 26420969
TI - Early endoscopic ultrasonography in acute biliary pancreatitis: A prospective
pilot study.
AB - AIM: To investigate the clinical usefulness of early endoscopic ultrasonography
(EUS) in the management of acute biliary pancreatitis (ABP). METHODS: All
consecutive patients entering the emergency department between January 2010 and
December 2012 due to acute abdominal pain and showing biochemical and/or
radiological findings consistent with possible ABP were prospectively enrolled.
Patients were classified as having a low, moderate, or high probability of common
bile duct (CBD) stones, according to the established risk stratification.
Exclusion criteria were: gastrectomy or patient in whom the cause of biliary
obstruction was already identified by ultrasonography. All enrolled patients
underwent EUS within 48 h of their admission. Endoscopic retrograde
cholangiopancreatography was performed immediately after EUS only in those cases
with proven CBD stones or sludge. The following parameters were investigated: (1)
clinical: age, sex, fever; (2) radiological: dilated CBD; and (3) biochemical:
bilirubin, AST, ALT, gGT, ALP, amylase, lipasis, PCR. Association between
presence of CBD stone at EUS and the individual predictors were assessed by
univariate logistic regression. Predictors significantly associated with CBD
stones (P < 0.05) were entered in a multivariate logistic regression model.
RESULTS: A total of 181 patients with pancreatitis were admitted to the emergency
department between January 2010 and December 2012. After exclusion criteria a
total of 71 patients (38 females, 53.5%, mean age 58 +/- 20.12 years, range 27-89
years; 33 males, 46.5%, mean age 65 +/- 11.86 years, range 41-91 years) were
included in the present study. The probability of CBD stones was considered low
in 21 cases (29%), moderate in 26 (37%), and high in the remaining 24 (34%). The
71 patients included in the study underwent EUS, which allowed for a complete
evaluation of the target sites in all the cases. The procedure was completed in a
mean time of 14.7 min (range 9-34 min), without any notable complications.The
overall CBD stone frequency was 44% (31 of 71), with a significant increase from
the group at low pretest probability to that at moderate (OR = 5.79, P = 0.01)
and high (OR = 4.25, P = 0.03) pretest probability. CONCLUSION: Early EUS in ABP
allows, if appropriate, immediate endoscopic treatment and significant spare of
unnecessary operative procedures thus reducing possible related complications.
PMID- 26420970
TI - Hybrid vs sequential therapy for eradication of Helicobacter pylori in Taiwan: A
prospective randomized trial.
AB - AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with
Helicobacter pylori (H. pylori) infection. METHODS: From March 2013 to May 2014,
one hundred and seventy-five H. pylori infected patients who had not been treated
for H. pylori before were randomized to receive either sequential therapy
(rabeprazole 20 mg and amoxicillin 1 g twice daily for 5 d, followed by
rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg twice daily for
5 d) or hybrid therapy (rabeprazole 20 mg and amoxicillin 1 g for 7 d, followed
by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole
500 mg twice daily for 7 d). H. pylori status was confirmed by positive results
of both rapid urease test and histology examination or a positive result of
culture. Eradication efficacy was assessed by follow-up endoscopy with rapid
urease test and histological examination 8 wk after the end of anti-H. pylori
therapy, or (13)C-urea breath test at least 4 wk after completion of treatment.
The primary outcome was H. pylori eradication by intention-to-treat (ITT) and per
protocol (PP) analyses. RESULTS: One hundred and sixty-seven patients (83
patients in the sequential group and 84 patients in the hybrid group) completed
the study. The compliance rates were 97.6% and 97.7% for the two groups,
respectively. The eradication rate was 78.2% for the sequential group and 92% for
the hybrid group by ITT analysis (P = 0.01). The eradication rate was 81.9% for
the sequential group and 96.4% for the hybrid group by PP analysis (P = 0.01).
Univariate analysis for the clinical and bacterial factors did not identify any
risk factors associated with treatment failure. Severe adverse events were
observed in 2.3% of patients in the sequential group and 2.4% of those in the
hybrid group. CONCLUSION: Due to a grade A (> 95%) success rate for H. pylori
eradication by PP analysis, similar compliance and adverse events, hybrid therapy
seems to be an appropriate eradication regimen in Taiwan.
PMID- 26420972
TI - Prognostic value of Muc5AC in gastric cancer: A meta-analysis.
AB - AIM: To assess the correlation between decreased Muc5AC expression and patients'
survival and clinicopathological characteristics by conducting a meta-analysis.
METHODS: Literature searches were performed in PubMed and EMBASE, and 11 studies
met our criteria. Summary hazard ratios or odds ratios (ORs) with 95% confidence
intervals (CIs) were calculated to estimate the effect. For the pooled analysis
of the correlation between decreased Muc5AC expression and clinicopathological
characteristics (tumour invasion depth, lymph node metastasis, tumour-node
metastasis stage, tumour size, venous invasion and lymphatic invasion), ORs and
their variance were combined to estimate the effect. RESULTS: Eleven
retrospective cohort studies comprising 2135 patients were included to assess the
association between Muc5AC expression and overall survival and/or
clinicopathological characteristics. Decreased Muc5AC expression was
significantly correlated with poor overall survival of gastric cancer patients
(pooled HR = 1.35, 95%CI: 1.08-1.7). Moreover, decreased Muc5AC expression was
also significantly associated with tumour invasion depth (pooled OR = 2.12,
95%CI: 1.56-2.87) and lymph node metastasis (pooled OR = 1.56, 95%CI: 1.00-2.44)
in gastric cancer. CONCLUSION: Decreased Muc5AC expression might be a poor
prognostic predictor for gastric cancer.
PMID- 26420971
TI - Chemoembolization alone vs combined chemoembolization and hepatic arterial
infusion chemotherapy in inoperable hepatocellular carcinoma patients.
AB - AIM: To compare the efficacy and safety of chemoembolization alone or
chemoembolization combined with hepatic arterial infusion chemotherapy (HAIC),
including oxaliplatin (OXA), 5-fluorouracil (5-FU) and folinic acid (CF), in
inoperable hepatocellular carcinoma (HCC) without distant metastasis. METHODS:
Eighty-four inoperable HCC patients were enrolled. Thirty-nine patients underwent
chemoembolization alone, and the other 45 patients underwent chemoembolization +
HAIC (OXA/5-FU/CF) treatment non-randomly. The progression free survival (PFS),
objective response rate (ORR), disease control rate (DCR) and adverse reactions
were compared between the two groups. RESULTS: A significant difference in the
ORR was observed between the chemoembolization alone and chemoembolization + HAIC
groups. There was no statistically significant difference in DCR between the two
groups. The median PFS (mPFS) showed a significant difference between the two
groups. For patients with BCLC stage A/B disease, with or without vessel
invasion, the chemoembolization + HAIC group showed better mPFS when compared to
chemoembolization alone, but no significant difference was found in patients with
BCLC stage C disease. The parameter of pain (grade III-IV) in the
chemoembolization + HAIC group was increased statistically. CONCLUSION:
Chemoembolization combined with HAIC with OXA/5-FU/CF may be safe and more
effective than chemoembolization alone for inoperable HCC patients without
distant metastasis.
PMID- 26420973
TI - Jejunitis and brown bowel syndrome with multifocal carcinogenesis of the small
bowel.
AB - This is the first report describing a case where prolonged, severe malabsorption
from brown bowel syndrome progressed to multifocally spread small bowel
adenocarcinoma. This case involves a female patient who was initially diagnosed
with chronic jejunitis associated with primary diffuse lymphangiectasia at the
age of 26 years. The course of the disease was clinically, endoscopically, and
histologically followed for 21 years until her death at the age 47 due to
multifocal, metastasizing adenocarcinoma of the small bowel. Multiple lipofuscin
deposits (so-called brown bowel syndrome) and severe jejunitis were observed
microscopically, and sections of the small bowel showed dense lymphoplasmacytic
infiltration of the lamina propria as well as blocked lymphatic vessels. After
several decades, multifocal nests of adenocarcinoma cells and extensive, flat,
neoplastic mucosal proliferations were found only in the small bowel, along with
a loss of the mismatch repair protein MLH1 as a long-term consequence of chronic
jejunitis with malabsorption. No evidence was found for hereditary nonpolyposis
colon carcinoma syndrome. This article demonstrates for the first time multifocal
carcinogenesis in the small bowel in a malabsorption syndrome in an enteritis
dysplasia-carcinoma sequence.
PMID- 26420974
TI - Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the
literature.
AB - Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare form of
undifferentiated carcinoma of the liver characterized by the presence of an
abundant lymphoid infiltrate. Here, a case of LEL-HCC is described. An 81-year
old woman with a chronic hepatitis C infection was referred to the general
surgery department of our hospital in August 2013 with a diagnosis of HCC. A past
ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third
segment of the liver. After a needle biopsy, the lesion was diagnosed as HCC. The
patient underwent surgery with a liver segmentectomy. Two additional nodes on the
gastric wall were detected during the surgical operation. The histology of the
removed specimen showed a poorly differentiated HCC with significant lymphoid
stroma. Immunohistochemical studies revealed that the epithelial component was
reactive for CK CAM5.2, CK8, CK18, CEA (polyclonal) and was focally positive for
hepar-1 and that the lymphoid infiltrate was positive for CD3, CD4 and CD8. The
tumor cells were negative for Epstein-Barr virus. The gastric nodes were
ultimately determined to be two small gastrointestinal stromal tumors (GISTs).
The synchronous occurrence of HCC and GIST is another very uncommon finding
rarely described in the literature. Here, we report the clinicopathological
features of our case, along with a review of the few cases present in the
literature.
PMID- 26420975
TI - Autoimmune-like hepatitis during masitinib therapy in an amyotrophic lateral
sclerosis patient.
AB - We report a case of acute severe hepatitis resulting from masitinib in a young
amyotrophic lateral sclerosis patient. Hepatotoxicity induced by masitinib, a
tyrosine kinase inhibitor, is usually transient with mild elevation of
transaminases, although acute hepatitis has been not reported to date. The
hepatitis was resolved after masitinib was discontinued and a combination of
prednisone and azathioprine was started. The transaminases returned to baseline
normal values five months later. This is the first case in the hepatitis
literature associated with masitinib. The autoimmune role of this drug-induced
liver injury is discussed. Physicians should be aware of this potential
complication.
PMID- 26420976
TI - Small bowel volvulus with jejunal diverticulum: Primary or secondary?
AB - Small bowel volvulus, which is torsion of the small bowel and its mesentery, is a
medical emergency, and is categorized as primary or secondary type. Primary type
often occurs without any apparent intrinsic anatomical anomalies, while the
secondary type is common clinically and could be caused by numerous factors
including postoperative adhesions, intestinal diverticulum, and/or tumors. Here,
we report a rare case of a 60-year-old man diagnosed with small bowel volvulus
using multidetector computed tomography (MDCT) angiography. Further discovery by
laparotomy showed one jejunal diverticulum, longer corresponding mesentery with a
narrower insertion, and a lack of mesenteric fat. This case report includes
several etiological factors of small bowel volvulus, and we discuss the possible
cause of small bowel volvulus in this patient. We also highlight the importance
of MDCT angiography in the diagnosis of volvulus and share our experience in
treating this disease.
PMID- 26420977
TI - Corticosteroid and nucleoside analogue for hepatitis B virus-related acute liver
failure.
AB - The early introduction of combination therapy of high-dose corticosteroid and
nucleoside analogue is beneficial for the rescue of severe acute exacerbation of
chronic hepatitis B.
PMID- 26420978
TI - Relationships Between Caregiver Violence Exposure, Caregiver Depression, and
Youth Behavioral Health Among Homeless Families.
AB - Homelessness affects a large and increasing number of families in the United
States, and exposure to violence and other potentially traumatic events is common
among homeless families. It is important to understand more about this population
and, more specifically, about the relationship between youth mental health and
caregiver mental health and trauma exposure among homeless families, in order to
better serve the needs of this vulnerable population. The objective of this study
is to explore the relationships between caregiver exposure to violence, caregiver
depression, and youth depression and behavioral problems among homeless families.
Preliminary findings indicate that among this sample of homeless families,
caregiver violence exposure has statistically significant relationships with both
youth behavioral problems and youth depression symptoms, as mediated by caregiver
depression. These findings indicate that youth behavioral health is associated
with caregiver mental health, which, in turn, is associated with caregiver trauma
exposure. This highlights the importance of taking into account adult mental
health while treating youth externalizing and internalizing behaviors and
ensuring that caregivers, too, have access to adequate treatment and supports.
Furthermore, this treatment should be trauma informed, given the link between
trauma and mental health.
PMID- 26420979
TI - Comparison of Capsule Endoscopy Findings to Subsequent Double Balloon
Enteroscopy: A Dual Center Experience.
AB - Background. There has been a growing use of both capsule endoscopy (CE) and
double balloon enteroscopy (DBE) to diagnose and treat patients with obscure
gastrointestinal blood loss and suspected small bowel pathology. Aim. To compare
and correlate sequential CE and DBE findings in a large series of patients at two
tertiary level hospitals in Wisconsin. Methods. An IRB approved retrospective
study of patients who underwent sequential CE and DBE, at two separate tertiary
care academic centers from May 2007 to December 2011, was performed. Results. 116
patients were included in the study. The mean age +/- SD was 66.6 +/- 13.2 years.
There were 56% males and 43.9% females. Measure of agreement between prior
capsule and DBE findings was performed using kappa statistics, which gave kappa
value of 0.396 with P < 0.001. Also contingency coefficient was calculated and
was found to be 0.732 (P < 0.001). Conclusions. Our study showed good overall
agreement between DBE and CE. Findings of angioectasia had maximum agreement of
69%.
PMID- 26420980
TI - Rhabdomyosarcoma: Advances in Molecular and Cellular Biology.
AB - Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and
adolescence. The two major histological subtypes of RMS are alveolar RMS, driven
by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually
genetically heterogeneous. The prognosis of RMS has improved in the past several
decades due to multidisciplinary care. However, in recent years, the treatment of
patients with metastatic or refractory RMS has reached a plateau. Thus, to
improve the survival rate of RMS patients and their overall well-being, further
understanding of the molecular and cellular biology of RMS and identification of
novel therapeutic targets are imperative. In this review, we describe the most
recent discoveries in the molecular and cellular biology of RMS, including
alterations in oncogenic pathways, miRNA (miR), in vivo models, stem cells, and
important signal transduction cascades implicated in the development and
progression of RMS. Furthermore, we discuss novel potential targeted therapies
that may improve the current treatment of RMS.
PMID- 26420982
TI - Not for the Last Time that I do Something for the First Time: A Time to Padhy!
PMID- 26420981
TI - Toxicity of polymeric nanoparticles in vivo and in vitro.
AB - Polybutylcyanoacrylate nanoparticles (PBCA NPs) are candidates for a drug
delivery system, which can cross the blood-brain barrier (BBB). Because little is
known about their toxicity, we exposed cells to PBCA NPs in vitro and in vivo and
monitored their life and death assays. PBCA NPs were fabricated with different
surfactants according to the mini-emulsion technique. Viabilities of HeLa and
HEK293 cells after NP incubation were quantified by analysing cellular metabolic
activity (MTT-test). We then repetitively injected i.v. rhodamine-labelled PBCA
NP variations into rats and monitored the survival and morphology of retrogradely
labelled neurons by in vivo confocal neuroimaging (ICON) for five weeks. To test
for carrier-efficacy and safety, PBCA NPs loaded with Kyotorphin were injected in
rats, and a hot plate test was used to quantify analgesic effects. In vitro, we
found dose-dependent cell death which was, however, only detectable at very high
doses and mainly seen in the cultures incubated with NPs fabricated with the
tensids SDS and Tween. However, the in vivo experiments did not show any NP
induced neuronal death, even with particles which were toxic at high dose in
vitro, i.e. NPs with Tween and SDS. The increased pain threshold at the hot plate
test demonstrated that PBCA NPs are able to cross the BBB and thus comprise a
useful tool for drug delivery into the central nervous system (CNS). Our findings
showing that different nanoparticle formulations are non-toxic have important
implications for the value of NP engineering approaches in medicine.
PMID- 26420984
TI - Development of Scintillators in Nuclear Medicine.
AB - High-quality image is necessary for accurate diagnosis in nuclear medicine. There
are many factors in creating a good image and detector is the most important one.
In recent years, several detectors are studied to get a better picture. The aim
of this paper is comparison of some type of these detectors such as thallium
activated sodium iodide bismuth germinate cesium activated yttrium aluminum
garnet (YAG: Ce) YAP: Ce "lutetium aluminum garnet activated by cerium" CRY018
"CRY019" lanthanum bromide and cadmium zinc telluride. We studied different
properties of these crystals including density, energy resolution and decay times
that are more important factors affecting the image quality.
PMID- 26420983
TI - Radioiodine Remnant Ablation: A Critical Review.
AB - Radioiodine remnant ablation (RRA) is considered a safe and effective method for
eliminating residual thyroid tissue, as well as microscopic disease if at all
present in thyroid bed following thyroidectomy. The rationale of RRA is that in
the absence of thyroid tissue, serum thyroglobulin (Tg) measurement can be used
as an excellent tumor marker. Other considerations are like the presence of
significant remnant thyroid tissue makes detection and treatment of nodal or
distant metastases difficult. Rarely, microscopic disease in the thyroid bed if
not ablated, in the future, could be a source of anaplastic transformation. On
the other hand, microscopic tumor emboli in distant sites could be the cause of
distant metastasis too. The ablation of remnant tissue would in all probability
eliminate these theoretical risks. It may be noted that all these are unproven
contentious issues except postablation serum Tg estimation that could be a good
tumor marker for detecting early biochemical recurrence in long-term follow-up
strategy. Radioactive iodine is administered as a form of "adjuvant therapy" for
remnant ablation. There have been several reports with regard to the administered
dose for remnant ablation. The first report of a prospective randomized clinical
trial was published from India by a prospective randomized study conducted at the
All India Institute of Medical Sciences, New Delhi in the year 1996. The study
reported that increasing the empirical (131)I initial dose to more than 50 mCi
results in plateauing of the dose-response curve and thus, conventional high-dose
remnant ablation needs critical evaluation. Recently, two important studies were
published: One from French group and the other from UK on a similar line.
Interestingly, all three studies conducted in three different geographical
regions of the world showed exactly similar conclusion. The new era of low-dose
remnant ablation has taken a firm scientific footing across the continents.
PMID- 26420985
TI - The Effect of Parallel-hole Collimator Material on Image and Functional
Parameters in SPECT Imaging: A SIMIND Monte Carlo Study.
AB - The collimator in single-photon emission computed tomography (SPECT) is a
critical component of the imaging system and plays an impressive role in the
imaging quality. In this study, the effect of the collimator material on the
radioisotopic image and its functional parameters was studied. The simulating
medical imaging nuclear detectors (SIMIND) Monte Carlo program was used to
simulate a Siemens E.CAM SPECT (Siemens Medical Solutions, Erlangen, Germany)
system equipped with a low-energy high-resolution (LEHR) collimator. The
simulation and experimental data from the SPECT imaging modality using (99m)Tc
were obtained on a point source and Jaszczak phantom. Seventeen high atomic
number materials were considered as LEHR collimator materials. In order to
determine the effect of the collimator material on the image and functional
parameters, the energy resolution, spatial resolution, contrast, and collimator
characteristics parameters such as septal penetration and scatter-to-primary
ratio were investigated. Energy spectra profiles, full width at half maximums
(FWHMs) (mm) of the point spread function (PSF) curves, system sensitivity, and
contrast of cold spheres of the Jaszczak phantom for the simulated and experiment
systems have acceptability superimposed. The results of FWHM and energy
resolution for the 17 collimators showed that the collimator made of 98% lead and
2% antimony could provide the best FWHM and energy resolution, 7.68 mm and 9.87%,
respectively. The LEHR collimator with 98% lead and 2% antimony offers the best
resolution and contrast when compared to other high atomic number metals and
alloys.
PMID- 26420986
TI - Dose Calibrator Linearity Testing: Radioisotope (99m)Tc or (18)F? An Alternative
for Reducing Costs in Nuclear Medicine Quality Control.
AB - Dose calibrator linearity testing is indispensable for evaluating the capacity of
this equipment in measuring radioisotope activities at different magnitudes, a
fundamental aspect of the daily routine of a nuclear medicine department, and
with an impact on patient exposure. The main aims of this study were to evaluate
the feasibility of substituting the radioisotope Fluorine-18 ((18)F) with
Technetium-99m ((99m)Tc) in this test, and to indicate it with the lowest
operational cost. The test was applied with sources of (99m)Tc (62 GBq) and (18)F
(12 GBq), the activities of which were measured at different times, with the
equipment preadjusted to measuring sources of (99m)Tc, (18)F, Gallium-67
((67)Ga), and Iodine-131 ((131)I). Over time, the average deviation between
measured and expected activities from (99m)Tc and (18)F were, respectively, 0.56
(+/-1.79)% and 0.92 (+/-1.19)%. The average ratios for 99(m)Tc source
experimental activity, when measured with the equipment adjusted for measuring
(18)F, (67)Ga, and (131)I sources, in real values, were, respectively, 3.42 (+/
0.06), 1.45 (+/-0.03), and 1.13 (+/-0.02), and those for the (18)F source
experimental activity, measured through adjustments of (99m)Tc, (67)Ga, and
(131)I, were, respectively, 0.295 (+/-0.004), 0.335 (+/-0.007), and 0.426 (+/
0.006). The adjustment of a simple exponential function for describing (99m)Tc
and (18)F experimental activities facilitated the calculation of the physical
half-lives of the radioisotopes, with a difference of about 1% in relation to the
values described in the literature. Linearity test results, when using (99m)Tc,
through being compatible with those acquired with (18)F, imply the possibility of
using both radioisotopes during linearity testing. Nevertheless, this
information, along with the high potential of exposure and the high cost of
(18)F, implies that (99m)Tc should preferably be employed for linearity testing
in clinics that normally use (18)F, without the risk of prejudicing either the
procedure itself or the guarantee of a high-quality nuclear medicine service.
PMID- 26420987
TI - Improving (18)F-Fluoro-D-Glucose-Positron Emission Tomography/Computed Tomography
Imaging in Alzheimer's Disease Studies.
AB - The goal was to improve Alzheimer's 2-deoxy-2-(18)F-fluoro-D-glucose ((18)F FDG)
positron emission tomography (PET)/computed tomography (CT) imaging through
application of a novel, hybrid Fourier-wavelet windowed Fourier transform (WFT)
restoration technique, in order to provide earlier and more accurate clinical
results. General Electric Medical Systems downward-looking sonar PET/CT 16 slice
system was used to acquire studies. Patient data were acquired according the
Alzheimer's disease Neuroimaging Initiative (ADNI) protocol. Here, we implemented
Fourier-wavelet regularized restoration, with a Butterworth low-pass filter,
order n = 6 and a cut-off frequency f = 0.35 cycles/pixel and wavelet
(Daubechies, order 2) noise suppression. The original (PET-O) and restored (PET
R) ADNI subject PET images were compared using the Alzheimer's discrimination
analysis by dedicated software. Forty-two PET/CT scans were used in the study.
They were performed on eleven ADNI subjects at intervals of approximately 6
months. The final clinical diagnosis was used as a gold standard. For three
subjects, the final clinical diagnosis was mild cognitive impairment and those 13
PET/CT studies were not included in the final comparison, as the result was
considered as inconclusive. Using the reminding 29 PET/CT studies (23 AD and 6
normal), the sensitivity and specificity of the PET-O and PET-R were calculated.
The sensitivity was 0.65 and 0.96 for PET-O and PET-R, respectively, and the
specificity was 0.67 and 0.50 for PET-O and PET-R. The accuracy was 0.66 and 0.86
for PET-O and PET-R, respectively. The results of the study demonstrated that the
accuracy of three-dimensional brain F-18 FDG PET images was significantly
improved by Fourier-wavelet restoration filtering.
PMID- 26420988
TI - Modified PISAPED Criteria in Combination with Ventilation Scintigraphic Finding
for Predicting Acute Pulmonary Embolism.
AB - This prospective clinical study aimed at assessing three pulmonary scintigraphic
algorithms to detect acute pulmonary embolism (PE): Lung ventilation/perfusion
(V/Q) scintigraphy along with modified prospective investigation of pulmonary
embolism diagnosis (PIOPED) criteria; lung perfusion scintigraphy along with
prospective investigative study of acute pulmonary embolism diagnosis (PISAPED)
criteria; and lung perfusion scan in combination with ventilation scan, along
with modified PISAPED criteria, which were newly developed. Patients with
suspicion of PE were eligible for this study if they had no abnormal chest x-ray.
Their diagnostic workup included a clinical assessment, a pulmonary V/Q
scintigraphy, and CT pulmonary angiography (CTPA), as well as a clinical outcome
assessment over a period of 24 weeks. Referred to the final clinical diagnosis of
patients, the sensitivity and specificity of each algorithm were evaluated. The
diagnostic performance of each algorithm by the area under the maximum likelihood
fitted receiver operating characteristic (ROC) curve was determined. With respect
to the PISAPED criteria, the sensitivity was 60.8% and specificity was 87.3%. No
patient was classified into nondiagnostic category. The PIOPED criteria showed
that the sensitivity was 95.0% and specificity was 88.2%, while 57.4% of the
patients were in nondiagnostic category. The areas under the ROC curve
constructed from the PISAPED criteria results and the modified PIOPED criteria
results were 0.734 and 0.859 (P < 0.01), respectively. The modified PISAPED
criteria demonstrated that the sensitivity was 83.8% and specificity was 89.1%.
No patient was classified into nondiagnostic category. The area under the ROC
curve constructed from modified PISAPED criteria was 0.864 (P < 0.01). Perfusion
scans used with ventilation scans and modified PISAPED criteria may increase the
diagnostic accuracy of pulmonary scintigraphy for acute PE, compared with the two
major algorithms.
PMID- 26420989
TI - Is there a Role for Gallium-67 Citrate SPECT/CT, in Patients with Renal
Impairment or Who are Renal Transplant Recipients, in Identifying and Localizing
Suspected Infection?
AB - To assess the added value of single-photon emission computed tomography/computed
tomography (SPECT/CT) in patients with end-stage renal failure (ESRF) or renal
transplant recipients in whom focal infection was suspected. Gallium-67 (Ga-67)
citrate scintigrams of 18 patients (10 in ESRF and eight with renal transplants)
were reviewed. Sites of abnormal uptake seen on the whole body and SPECT were
noted. A SPECT/CT was also reviewed to see if additional information could be
obtained. Imaging results were compared with the final diagnosis. Overall, 14 out
of 18 (78%) patients had a proven cause to explain symptoms while four patients
did not have a final cause identified. Infection was proven in the final
diagnosis in 12 out of 14 (86%) patients. Of the 10 patients with ESRF, six had
confirmed infection with the Ga-67 citrate study correctly identifying five out
of six (83%) patients, and SPECT/CT providing additional information in four out
of five (80%) patients. In the eight renal transplant recipients, six had a
confirmed source of infection (all identified by the Ga-67 citrate study).
SPECT/CT provided additional information in two out of six (33%) patients. Ga-67
citrate imaging had an overall sensitivity of 13/14 (93%), with one false
negative. SPECT/CT provided an additional contribution in eight out of 18 (44%)
patients by better defining the location/extent of infection and differentiating
the physiological from the pathological uptake.
PMID- 26420990
TI - Designing of High-Volume PET/CT Facility with Optimal Reduction of Radiation
Exposure to the Staff: Implementation and Optimization in a Tertiary Health Care
Facility in India.
AB - Positron emission tomography (PET) has been in use for a few decades but with its
fusion with computed tomography (CT) in 2001, the new PET/CT integrated system
has become very popular and is now a key influential modality for patient
management in oncology. However, along with its growing popularity, a growing
concern of radiation safety among the radiation professionals has become evident.
We have judiciously developed a PET/CT facility with optimal shielding, along
with an efficient workflow to perform high volume procedures and minimize the
radiation exposure to the staff and the general public by reducing unnecessary
patient proximity to the staff and general public.
PMID- 26420991
TI - The Relationship Between Some Complete Blood Count Parameters and Myocardial
Perfusion: A Scintigraphic Approach.
AB - Recent studies have shown that there is a relationship between some inflammatory
and biochemical markers derived from complete blood count (CBC) such as
neutrophil/lymphocyte (N/L) ratio, platelet/lymphocyte (P/L) ratio, platelet
distribution width (PDW), red blood cell distribution width (RDW), and coronary
artery disease (CAD). The aim of this study was to determine N/L ratio, P/L
ratio, PDW values, and RDW values, which are associated with myocardial perfusion
in patients diagnosed with CAD. This study included 262 patients (149 with
myocardial ischemia/infarction and 113 with normal myocardial perfusion)
undergoing myocardial perfusion scintigraphy (MPS) with CBC within 90 days of
MPS. Myocardial perfusion parameters such as summed stress score and summed
difference score (SDS) were compared with N/L ratio, P/L ratio, PDW values, and
RDW values. Neutrophil counts and N/L ratios were significantly higher in
patients diagnosed with myocardial ischemia and/or infarct. However, there was no
statistically significant relationship between myocardial perfusion abnormalities
and P/L ratio, PDW values, and RDW values. This study showed that N/L ratio is
related to myocardial ischemia/infarction and correlated to left ventricular
ejection fraction (LVEF).
PMID- 26420992
TI - V/Q Matched Defect Larger than Hiatal Hernia Itself.
AB - We present the case report of a patient 83 year old female who developed
progressive shortness of breath and subsequently underwent scintigraphic
evaluation of her symptoms with a ventilation/perfusion scintigraphic exam. A
matched perfusion defect was seen involving the basal segments of the left lower
lobe. Following this, the patient was examined with a contrast enhanced CT of the
chest to further investigate the defect, which revealed compression of the
bronchi and vasculature of the left lower lobe basal segments by the hernia
larger than the actual hernia. To our knowledge there has not been a case report
of a large hiatal hernia as a cause of matched lower lobe defect.
PMID- 26420993
TI - Os Trigonum - Sheer Incidental or Quite Significant? Single Photon Emission
Computed Tomography/Computed Tomography's Role in a Case of Ankle Impingement.
AB - Accessory ossicles are widely prevalent in the ankle and foot. Although they are
often asymptomatic, they can present clinically with symptoms at times. When they
occur bilaterally in a patient who presents with unilateral complaints, it is
clinically difficult to attribute the symptoms to the presence of these common
anatomic variants. One needs specific imaging to assess the clinical relevance of
the accessory ossicles, in order to tailor the treatment plan. The case presented
in this article is one such example, where the patient presented with chronic
unilateral ankle pain and initial radiographs revealed bilateral os trigonum and
os subtibiale. He underwent a technetium-99m methyl diphosphonate (Tc-99m MDP)
bone scan and single photon emission computed tomography/computed tomography
(SPECT/CT). The Tc-99m MDP scan showed a focal uptake in the ankle of concern.
SPECT/CT complemented the finding by exactly localizing the uptake to the
posterior subtalar joint and around the os trigonum, thereby pointing to the
diagnosis of os trigonum syndrome.
PMID- 26420994
TI - Indium-111 Capromab Pendetide (ProstaScint((r))) Demonstrates Renal Cell
Carcinoma and Aortocaval Nodal Metastases from Prostate Adenocarcinoma.
AB - A 62-year-old male with a history of radical prostatectomy for a Gleason 9 (4 +
5) pT3N0Mx prostate cancer presented with rising prostate-specific antigen of 9.0
ng/dl. A contrast-enhanced computerized tomography (CT) revealed an enhancing
left upper pole renal mass and aortocaval lymph nodes. Indium (In)-111 Capromab
Pendetide (ProstaScint((r))) single-photon emission computerized tomography-CT
showed abnormal increased uptake in left renal mass and aortocaval lymph nodes
with no uptake in the prostate bed or pelvic lymph nodes. He underwent left
radical nephrectomy and dissection of aortocaval lymph nodes. Pathology showed
renal clear cell carcinoma and metastatic prostate adenocarcinoma involving
aortocaval lymph nodes. Our case demonstrates a rare combination of two different
malignancies, prostate cancer and clear cell renal cell cancer, showing In-111
ProstaScint((r)) uptake. Though ProstaScint((r)) uptake in renal cell carcinoma
and in metastatic aortocaval lymph nodes from prostate cancer may be seen in
clinical practice, this combination has not been reported previously.
PMID- 26420995
TI - Nuclear Medicine to Evaluate Complications of Cerebral Shunts: Two Cases and
Review of Literature.
AB - We present two cases of cerebral shunts - a ventriculopleural shunt and a
ventriculoperitoneal shunt, with their associated complications. We also hope to
provide a comprehensive literature review on various imaging modalities,
including nuclear medicine studies in evaluating cerebral shunt complications.
PMID- 26420996
TI - Radiosynovectomy of Proximal Interphalangeal Joint Synovitis in Rheumatoid
Arthritis Treated with Rhenium-188 Labeled Tin-colloid and Imaging with Single
photon Emission Computerized Tomography/Computed Tomography: A First Case Report.
AB - Rheumatoid arthritis (RA) is a chronic disease that is mainly characterized by
the asymmetric erosive synovitis, particularly affecting peripheral joints.
Radiation synovectomy or radiosynovectomy (RSV), also known as
radiosynoviorthesis was first described in 1950's as an adjuvant treatment for
RA. RSV is based on the irradiation of the joint synovium by the intra-articular
administration of various beta-emitting radiopharmaceuticals. As a generator
produced beta-emitting radionuclide, the importance of rhenium-188 (Re-188) for
radionuclide therapy is increasing rapidly. There are previous reports which used
Re-188 tin colloid in knee joint synovitis, but use of Re-188 tin colloid in
small joint is not yet reported. We describe the use of Re-188 tin colloid in a
45-year-old female who presented with right 4(th) proximal interphalangeal joint
synovitis due to rheumatoid arthritis.
PMID- 26420997
TI - Colorectal Cancer with Uncommon Metastatic Spread.
AB - The prevalence of bone metastases from colorectal cancer (CRC) is quite low and
the presence of isolated osseous metastases at the time of diagnosis or the onset
of bone metastases without other organ involvement during follow-up is even
lower. Here, we present an interesting case of diffuse skeletal metastases from
CRC in which both the atypical presentation of the metastatic spread and the
presence of infective comorbidities created some troubles in getting the final
diagnosis.
PMID- 26420998
TI - Lynch Syndrome Associated Colon Adenocarcinoma Resembling Lymphoma on Fluoro
Deoxyglucose-Positron Emission Tomography/Computed Tomography.
AB - The patient was a 46-year-old Asian male diagnosed with lynch syndrome associated
colon adenocarcinoma in the right ascending colon. A presurgical staging 18
fluoro-deoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)
found increased metabolic activity in the cervical, axillary, mediastinal,
supraclavicular, para-aortic and mesenteric lymph nodes. This pattern of
metastasis was very unusual for lynch syndrome associated colon adenocarcinoma
and the involvement of those lymph nodes resembles the pattern of spread of
lymphoma. He underwent right hemicolectomy and he was subsequently treated with
12 cycles of folinic acid (leucovorin), fluorouracil (5-FU), irinotecan. A
restaging FDG-PET/CT at the end of the chemotherapy showed interval decrease in
size and metabolic activity in the affected lymph nodes. FDG-PET/CT is a useful
imaging modality in following-up the treatment response in colon adenocarcinoma.
PMID- 26420999
TI - Segmental Considerations in Colonoscopy Recommendations for Investigating Focal
Colonic FDG Activity on PET/CT.
PMID- 26421000
TI - Conversion of Saccharides into Formic Acid using Hydrogen Peroxide and a
Recyclable Palladium(II) Catalyst in Aqueous Alkaline Media at Ambient
Temperatures.
AB - We have developed an effective method that converts a variety of mono- and
disaccharides into formic acid predominantly. Our recyclable NHC-amidate
palladium(II) catalyst facilitated oxidative degradation of carbohydrates without
using excess oxidant. Stoichiometric amounts of hydrogen peroxide and sodium
hydroxide were employed at ambient temperatures.
PMID- 26421001
TI - Jacaric acid inhibits the growth of murine macrophage-like leukemia PU5-1.8 cells
by inducing cell cycle arrest and apoptosis.
AB - BACKGROUND: Conjugated linolenic acids (CLN) refer to the positional and
geometric isomers of octadecatrienoic acids with three conjugated double bonds
(C18:3). Previous researches have demonstrated that CLN can inhibit the growth of
a wide variety of cancer cells, whereas the modulatory effect of CLN on various
myeloid leukemia cells remains unclear. This study aims at demonstrating the in
vitro anti-tumor effect and action mechanisms of jacaric acid, a CLN isomer which
is present in jacaranda seed oil, on the murine macrophage-like leukemia PU5-1.8
cells. METHODS AND RESULTS: It was found that jacaric acid inhibited the
proliferation of PU5-1.8 cells in a time- and concentration-dependent manner, as
determined by the MTT reduction assay and by using CyQUANT((r)) NF Cell
Proliferation Assay Kit, while it exerted minimal cytotoxicity on normal murine
cells. Besides, the reactive oxygen species production in jacaric acid-treated
PU5-1.8 cells was elevated in a concentration-dependent mannar. Flow cytometric
analysis revealed the induction of G0/G1 cell cycle arrest, accompanied by a
decrease in CDK2 and cyclin E proteins. Jacaric acid also triggered apoptosis as
reflected by induction of DNA fragmentation, phosphatidylserine externalization,
mitochondrial membrane depolarization, up-regulation of pro-apoptotic Bax protein
and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL proteins. CONCLUSIONS: Our
results demonstrated the growth-inhibitory effect of jacaric acid on PU5-1.8
cells through inducing cell cycle arrest and apoptosis, while exhibiting minimal
cytotoxicity to normal murine cells. Therefore, jacaric acid is a potential
candidate for the treatment of some forms of myeloid leukemia with minimal
toxicity and fewer side effects.
PMID- 26421002
TI - PDK1-mTOR signaling pathway inhibitors reduce cell proliferation in MK2206
resistant neuroblastoma cells.
AB - PURPOSE: AKT plays a pivotal role in the signal transduction of cancer cells.
MK2206, an AKT inhibitor, has been shown to be an effective anti-cancer drug to a
variety of cancer cell lines. However, some cancer cells acquire resistance to
MK2206 and new strategies to suppress these cell lines remain to be developed.
EXPERIMENTAL DESIGN: Acquired MK-2206-resistant neuroblastoma (NB) cell sublines
were induced by stepwise escalation of MK-2206 exposure (4-12 weeks). MTT assay
was used to validate cell proliferation. Flow cytometry was performed for cell
cycle analysis. Western blot assay was used for cell signaling study. RESULTS:
MK2206 (5-10 umol) significantly suppressed cell growth of MK2206 non-resistant
NB cells (LAN-1, KP-N-SIFA, NB-19 and SK-N-DZ), but is less efficient in
inhibiting that of resistant sublines, even after 2-week MK2206-free incubation.
MK2206 acted in mTOR-S6K dependent and independent methods. MK-2206 resistant
sublines (LAN-1-MK, KP-N-SIFA-MK, and SK-N-DZ-MK) showed lower IC50 of GSK2334470
(PDK1 inhibitor). The cell growth of all sublines was prohibited by AZD8805 (mTOR
inhibitor), with IC50 of AZD8805 3-10 times lower than MK2206 non-resistant
cells. The signaling profiles of these resistant sublines were characterized by
elevated PDK1-mTOR-S6K activity, accompanying by low phosphorylation of AKT
compared with non-resistant counterparts. GSK2334470 and AZD8055 effectively
inhibited phosphorylation of PDK1 and mTOR, respectively, and induced higher G0
G1 ratio in LAN-1-MK than that in LAN-1 as well. PDK1 and mTOR inhibitors
effected on phosphorylation of GSK3beta in some of resistant sublines.
CONCLUSION: NB cells can acquire MK2206 resistance after exposure for 4-12 weeks.
Resistant cells feature reliance on PDK1-mTOR-S6K pathway and are more sensitive
to PDK1 and mTOR inhibitors than the non-resistant counterparts. Thus,
suppression of PDK1-mTOR-S6K signaling pathway is an effective way to overcome
the MK2206 resistance, and this may be a promising strategy for targeted therapy.
PMID- 26421003
TI - Evaluation in medical education: A topical review of target parameters, data
collection tools and confounding factors.
AB - BACKGROUND AND OBJECTIVE: Evaluation is an integral part of education in German
medical schools. According to the quality standards set by the German Society for
Evaluation, evaluation tools must provide an accurate and fair appraisal of
teaching quality. Thus, data collection tools must be highly reliable and valid.
This review summarises the current literature on evaluation of medical education
with regard to the possible dimensions of teaching quality, the psychometric
properties of survey instruments and potential confounding factors. METHODS: We
searched Pubmed, PsycINFO and PSYNDEX for literature on evaluation in medical
education and included studies published up until June 30, 2011 as well as
articles identified in the "grey literature". RESULTS are presented as a
narrative review. RESULTS: We identified four dimensions of teaching quality:
structure, process, teacher characteristics, and outcome. Student ratings are
predominantly used to address the first three dimensions, and a number of
reliable tools are available for this purpose. However, potential confounders of
student ratings pose a threat to the validity of these instruments. Outcome is
usually operationalised in terms of student performance on examinations, but
methodological problems may limit the usability of these data for evaluation
purposes. In addition, not all examinations at German medical schools meet
current quality standards. CONCLUSION: The choice of tools for evaluating medical
education should be guided by the dimension that is targeted by the evaluation.
Likewise, evaluation results can only be interpreted within the context of the
construct addressed by the data collection tool that was used as well as its
specific confounding factors.
PMID- 26421005
TI - Nonlinear Inertia Weighted Teaching-Learning-Based Optimization for Solving
Global Optimization Problem.
AB - Teaching-learning-based optimization (TLBO) algorithm is proposed in recent years
that simulates the teaching-learning phenomenon of a classroom to effectively
solve global optimization of multidimensional, linear, and nonlinear problems
over continuous spaces. In this paper, an improved teaching-learning-based
optimization algorithm is presented, which is called nonlinear inertia weighted
teaching-learning-based optimization (NIWTLBO) algorithm. This algorithm
introduces a nonlinear inertia weighted factor into the basic TLBO to control the
memory rate of learners and uses a dynamic inertia weighted factor to replace the
original random number in teacher phase and learner phase. The proposed algorithm
is tested on a number of benchmark functions, and its performance comparisons are
provided against the basic TLBO and some other well-known optimization
algorithms. The experiment results show that the proposed algorithm has a faster
convergence rate and better performance than the basic TLBO and some other
algorithms as well.
PMID- 26421006
TI - CDMBE: A Case Description Model Based on Evidence.
AB - By combining the advantages of argument map and Bayesian network, a case
description model based on evidence (CDMBE), which is suitable to continental law
system, is proposed to describe the criminal cases. The logic of the model adopts
the credibility logical reason and gets evidence-based reasoning quantitatively
based on evidences. In order to consist with practical inference rules, five
types of relationship and a set of rules are defined to calculate the credibility
of assumptions based on the credibility and supportability of the related
evidences. Experiments show that the model can get users' ideas into a figure and
the results calculated from CDMBE are in line with those from Bayesian model.
PMID- 26421004
TI - Guillain-Barre syndrome: clinical profile and management.
AB - INTRODUCTION: Guillain-Barre syndrome (GBS) is a fulminant polyradiculoneuropathy
that is acute, frequently severe and autoimmune in nature. Etiology of GBS is
incompletely understood, prognosis is usually good with early detection and
prompt treatment. This retrospective study was done to evaluate clinical profile,
epidemiological, laboratory, and electrodiagnostic features of patients with GBS
and mode of management, complications and prognostic factors. METHODS: Data of
1,166 patients admitted with GBS or presented to outpatient department (previous
medical records) with GBS between January 2003 and January 2014 were analyzed.
RESULTS: No difference in genders noted. Around 35% of patients are above 50
years of age. Poor control of diabetes with mean HbA1c of 8.1 +/- 2.11 is found
on analysis. Seasonal occurrence in GBS is prominent in winter 484 (41.50%) and
mechanically ventilated were 449 (38.50%) patients. 48 (4.11%) deaths were
attributed to GBS. Neurological analysis revealed cranial nerve involvement in
407 (34.90%) patients, facial palsy in 401 (34.39%) and ataxia in 88 (7.54%)
patients. Most patients in plasma exchange group belonged to the lower socio
economic status. Mean cerebrospinal fluid (CSF) protein levels was (n=962) 113.8
+/- 11.8 mg/dl. Conduction block determined indirectly by absent H-reflex was
noted in 891 (90.64%) patients. No difference in complications and outcome is
found in treatment regimens of intravenous immunoglobulin (IVIG) and plasma
exchange. CONCLUSION: Seasonal occurrence predominantly in winter is noted. Peak
flow test may be a predictor of assessing requirement of mechanical ventilation
and prognosis. Conduction block is the major abnormality noted in
electrophysiological studies and proximal nerve segment assessing with Erb's
point stimulation has high predictive value. IVIG treatment is more expensive but
is associated with less duration of hospital stay.
PMID- 26421007
TI - BF3.Et2O Catalysed 4-Aryl-3-phenyl-benzopyrones, Pro-SERMs, and Their
Characterization.
AB - We have synthesized the novel 4-(4-hydroxy-benzyl)-3-phenyl-chromen-2-one which
is a precursor of SERMs with a smaller number of steps and good yield. Two
methodologies for the synthesis have been worked out. Anhydrous BF3.Et2O
catalyzed reaction was found to be selective for product formation while
anhydrous AlCl3, FeCl3, and SnCl4 catalyzed ones were nonselective.
PMID- 26421008
TI - Validated HPTLC Method for Quantification of Luteolin and Apigenin in Premna
mucronata Roxb., Verbenaceae.
AB - A simple, rapid, and precise high-performance thin-layer chromatographic method
was developed for quantitative estimation of luteolin and apigenin in Premna
mucronata Roxb., family Verbenaceae. Separation was performed on silica gel 60
F254 HPTLC plates using toluene : ethyl acetate : formic acid (6 : 4 : 0.3) as
mobile phase for elution of markers from extract. The determination was carried
out in fluorescence mode using densitometric absorbance-reflection mode at 366 nm
for both luteolin and apigenin. The methanolic extract of Premna mucronata was
found to contain 10.2 mg/g % luteolin and 0.165 mg/g % of apigenin. The method
was validated in terms of linearity, LOD and LOQ, accuracy, precision, and
specificity. The calibration curve was found to be linear between 200 and 1000
ng/band for luteolin and 50 and 250 ng/band for apigenin. For luteolin and
apigenin, the limit of detection was found to be 42.6 ng/band and 7.97 ng/band
while the limit of quantitation was found to be 129.08 ng/band and 24.155
ng/band, respectively. This developed validated method is capable of quantifying
and resolving luteolin and apigenin and can be applicable for routine analysis of
extract and plant as a whole.
PMID- 26421009
TI - Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7
after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats.
AB - Background. The accompanied role of Mas receptor (MasR), bradykinin (BK), and
female sex hormone on renal blood flow (RBF) response to angiotensin 1-7 is not
well defined. We investigated the role of MasR antagonist (A779) and BK on RBF
response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods.
Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV) for two
weeks. Catheterized animals were subjected to BK and A799 infusion and mean
arterial pressure (MAP), RBF, and renal vascular resistance (RVR) responses to
Ang 1-7 (0, 100, and 300 ng kg(-1) min(-1)) were determined. Results. Percentage
change of RBF (%RBF) in response to Ang1-7 infusion increased in a dose-dependent
manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1
7 in OVE group was greater than OV group significantly (P < 0.05). Infusion of
300 ng kg(-1) min(-1) Ang 1-7 increased RBF by 6.9 +/- 1.9% in OVE group versus
0.9 +/- 1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7
in OV group was greater than OVE group insignificantly. Conclusion.
Coadministration of BK and A779 compared to BK alone increased RBF response to
Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol
treated rats.
PMID- 26421010
TI - Low Growth Hormone Levels in Short-Stature Children with Pituitary Hyperplasia
Secondary to Primary Hypothyroidism.
AB - Objective. The follow-up of GH levels in short-stature children with pituitary
hyperplasia secondary to primary hypothyroidism (PPH) is reported in a few cases.
We aimed to observe changes in GH secretion in short-stature children with PPH.
Methods. A total of 11 short-stature children with PPH accompanied by low GH
levels were included. They received levothyroxine therapy after diagnosis. Their
thyroid hormones, IGF-1, PRL, and pituitary height were measured at baseline and
3 months after therapy. GH stimulation tests were performed at baseline and after
regression of thyroid hormones and pituitary. Results. At baseline, they had
decreased GH peak and FT3 and FT4 levels and elevated TSH levels. Decreased IGF-1
levels were found in seven children. Elevated PRL levels and positive thyroid
antibodies were found in 10 children. The mean pituitary height was 14.3 +/- 3.8
mm. After 3 months, FT3, FT4, and IGF-1 levels were significantly increased (all
p < 0.01), and values of TSH, PRL, and pituitary height were significantly
decreased (all p < 0.001). After 6 months, pituitary hyperplasia completely
regressed. GH levels returned to normal in nine children and were still low in
two children. Conclusion. GH secretion can be resolved in most short-stature
children with PPH.
PMID- 26421011
TI - Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action.
AB - In the last decade, ample evidence has demonstrated the growing importance of
androgen receptor (AR) CAG repeat polymorphism in andrology. This genetic
parameter is able to condition the peripheral effects of testosterone and
therefore to influence male sexual function and fertility, cardiovascular risk,
body composition, bone metabolism, the risk of prostate and testicular cancer,
the psychiatric status, and the onset of neurodegenerative disorders. In this
review, we extensively discuss the literature data and identify a role for AR CAG
repeat polymorphism in conditioning the systemic testosterone effects. In
particular, our main purpose was to provide an updated text able to shed light on
the many and often contradictory findings reporting an influence of CAG repeat
polymorphism on the targets of testosterone action.
PMID- 26421013
TI - Some Rare Earth Elements Analysis by Microwave Plasma Torch Coupled with the
Linear Ion Trap Mass Spectrometry.
AB - A sensitive mass spectrometric analysis method based on the microwave plasma
technique is developed for the fast detection of trace rare earth elements (REEs)
in aqueous solution. The plasma was produced from a microwave plasma torch (MPT)
under atmospheric pressure and was used as ambient ion source of a linear ion
trap mass spectrometer (LTQ). Water samples were directly pneumatically nebulized
to flow into the plasma through the central tube of MPT. For some REEs, the
generated composite ions were detected in both positive and negative ion modes
and further characterized in tandem mass spectrometry. Under the optimized
conditions, the limit of detection (LOD) was at the level 0.1 ng/mL using MS(2)
procedure in negative mode. A single REE analysis can be completed within 2~3
minutes with the relative standard deviation ranging between 2.4% and 21.2% (six
repeated measurements) for the 5 experimental runs. Moreover, the recovery rates
of these REEs are between the range of 97.6%-122.1%. Two real samples have also
been analyzed, including well and orange juice. These experimental data
demonstrated that this method is a useful tool for the field analysis of REEs in
water and can be used as an alternative supplement of ICP-MS.
PMID- 26421014
TI - Modulation Effects of Curcumin on Erythrocyte Ion-Transporter Activity.
AB - Curcumin ((1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione),
the yellow biphenolic pigment isolated from turmeric (Curcuma longa), has various
medicinal benefits through antioxidation, anti-inflammation, cardiovascular
protection, immunomodulation, enhancing of the apoptotic process, and
antiangiogenic property. We explored the effects of curcumin in vitro (10(-5) M
to 10(-8) M) and in vivo (340 and 170 mg/kg b.w., oral) on Na(+)/K(+) ATPase
(NKA), Na(+)/H(+) exchanger (NHE) activity, and membrane lipid hydroperoxides
(ROOH) in control and experimental oxidative stress erythrocytes of Wistar rats.
As a result, we found that curcumin potently modulated the membrane transporters
activity with protecting membrane lipids against hydro-peroxidation in control as
well as oxidatively challenged erythrocytes evidenced by stimulation of NKA,
downregulation of NHE, and reduction of ROOH in the membrane. The observed
results corroborate membrane transporters activity with susceptibility of
erythrocyte membrane towards oxidative damage. Results explain the protective
mechanism of curcumin against oxidative stress mediated impairment in ions
transporters activity and health beneficial effects.
PMID- 26421015
TI - Predictors of Outcome and Severity in Adult Filipino Patients with Febrile
Neutropenia.
AB - Aim. The study aimed to describe the profile of Filipino febrile neutropenia
patients and to determine parameters associated with severe outcomes. Methods.
This is a retrospective study of Filipino febrile neutropenia patients admitted
to the Philippine General Hospital. Patients were described in terms of clinical
presentation and stratified according to the presence or absence of severe
outcomes. Prognostic factors were then identified using regression analysis.
Results. 115 febrile episodes in 102 patients were identified. Regression
analysis yielded prolonged fever >7 days prior to admission (OR 2.43; 95% CI,
0.77-7.74), isolation of a pathogen on cultures (OR 2.69; 95% CI, 1.04-6.98), and
nadir absolute neutrophil count (ANC) < 100 during admission (OR 1.96; 95% CI,
0.75-5.12) as significant predictors of poor outcome. Factors that significantly
correlated with better outcome were granulocyte colony-stimulating factor (G-CSF)
use (OR 0.31; 95% CI, 0.11-0.85) and completeness of antibiotic therapy (OR 0.26;
95% CI, 0.10-0.67). Conclusion. Prolonged fever >7 days prior to admission,
positive pathogen on cultures, and nadir ANC < 100 during admission predicted
severe outcomes, whereas G-CSF use and complete antibiotic therapy were
associated with better outcomes. These prognostic variables might be useful in
identifying patients that need more intensive treatment and monitoring.
PMID- 26421012
TI - Gallbladder Cancer in the 21st Century.
AB - Gallbladder cancer (GBC) is an uncommon disease in the majority of the world
despite being the most common and aggressive malignancy of the biliary tree.
Early diagnosis is essential for improved prognosis; however, indolent and
nonspecific clinical presentations with a paucity of pathognomonic/predictive
radiological features often preclude accurate identification of GBC at an early
stage. As such, GBC remains a highly lethal disease, with only 10% of all
patients presenting at a stage amenable to surgical resection. Among this select
population, continued improvements in survival during the 21st century are
attributable to aggressive radical surgery with improved surgical techniques.
This paper reviews the current available literature of the 21st century on PubMed
and Medline to provide a detailed summary of the epidemiology and risk factors,
pathogenesis, clinical presentation, radiology, pathology, management, and
prognosis of GBC.
PMID- 26421016
TI - The Relationship of the Facial Nerve to the Condylar Process: A Cadaveric Study
with Implications for Open Reduction Internal Fixation.
AB - Introduction. The mandibular condyle is the most common site of mandibular
fracture. Surgical treatment of condylar fractures by open reduction and internal
fixation (ORIF) demands direct visualization of the fracture. This project aimed
to investigate the anatomic relationship of the tragus to the facial nerve and
condylar process. Materials and Methods. Twelve fresh hemicadavers heads were
used. An extended retromandibular/preauricular approach was utilized, with the
incision being based parallel to the posterior edge of the ramus. Measurements
were obtained from the tragus to the facial nerve and condylar process. Results.
The temporozygomatic division of the facial nerve was encountered during each
approach, crossing the mandible at the condylar neck. The mean tissue depth
separating the facial nerve from the condylar neck was 5.5 mm (range: 3.5 mm-7
mm, SD 1.2 mm). The upper division of the facial nerve crossed the posterior
border of the condylar process on average 2.31 cm (SD 0.10 cm) anterior to the
tragus. Conclusions. This study suggests that the temporozygomatic division of
the facial nerve will be encountered in most approaches to the condylar process.
As visualization of the relationship of the facial nerve to condyle is often
limited, recognition that, on average, 5.5 mm of tissue separates condylar
process from nerve should help reduce the incidence of facial nerve injury during
this procedure.
PMID- 26421017
TI - Bilateral Spontaneous Perirenal Hemorrhage due to Initial Presentation of
Polyarteritis Nodosa.
AB - Spontaneous perirenal hemorrhage (SPH) is uncommon but can be a life-threatening
condition which is associated with flank or abdominal pain and hypovolemia. The
etiologies of SPH include tumor, vascular disease, and infection. Among the
vascular diseases, polyarteritis nodosa (PAN) is common cause of the SPH.
However, patients with PAN usually complain of nonspecific symptoms and the
incidence of PAN is relatively rare. So, diagnosis is difficult even though
tissue biopsy and angiography help to confirm the PAN. Particularly bilateral
perirenal hemorrhage is very rare complication in patients with PAN. We reported
a case of bilateral perirenal hemorrhage in the patients with PAN who have
continued to take exogenous sex hormone.
PMID- 26421018
TI - New-Onset Myocarditis in an Immunocompetent Adult with Acute Metapneumovirus
Infection.
AB - Introduction. A number of viruses have been implicated in viral myocarditis;
however, there has been no previous report of human metapneumovirus (hMPV)
causing this condition. Discovered in 2001, hMPV is typically associated with
upper respiratory illness, mainly affecting children. Case Presentation. We
report the case of a 25-year-old man with acute systolic heart failure from viral
myocarditis secondary to the hMPV. The patient was initially admitted to the
general medical ward but developed increasing oxygen requirements resulting in
transfer to the cardiac intensive care unit. Cardiac magnetic resonance imaging
was used to help confirm the diagnosis. He was treated with intravenous
diuretics, and afterload and preload agents, and he was subsequently discharged
home after seven days of hospitalization. Discussion. hMPV is typically a
respiratory pathogen; however, it was associated with in myocarditis in our
patient. Due to the recent ability to detect this virus, we may see more cases of
this, particularly during peak months of infection. Conclusion. This is the first
case description of myocarditis associated with hMPV infection.
PMID- 26421019
TI - Health-related quality of life in patients with primary immunodeficiency disease.
AB - Primary immunodeficiency disease (PIDD) with hypogammaglobulinemia is
characterized by recurrent and severe bacterial infections and IgG replacement is
the standard of care in many of these patients. Health-related quality of life
(HRQOL) is becoming increasingly recognized as a factor that affects patient well
being and treatment preferences. In an effort to better understand what factors
affect HRQOL in patients with PIDD, we reviewed the published literature that
used standardized instruments for the measurement of HRQOL. We investigated HRQOL
in PIDD patients compared with normal controls and patients with other chronic
diseases; we also investigated the impact of treatment administration on patient
satisfaction. The most commonly encountered health-related quality of life
instruments were the child heath questionnaire parental form 50, short form 36,
PedsQL 4.0, Lansky's play performance scale, and Life Quality Index. Patients
with PIDD scored significantly lower on many of the instruments compared with
normal controls. Also, while it appears that many patients appreciate home-based
and subcutaneous IgG replacement therapy, patient satisfaction ultimately
involves various clinical factors and individual patient preferences. By further
analyzing what factors impact HRQOL, therapy adjustments can be made to maximize
patient well-being and minimize disease impact on daily functioning.
PMID- 26421021
TI - Liver Transplantation in Liver Cirrhosis Patients Accompanied by Portal Vein
Thrombosis.
AB - Benign portal vein thrombosis (PVT) is a challenging complication of an otherwise
successful liver transplantation. PVT is caused by various conditions and results
in pathologic hemodynamics of hepatofugal diversion of porto-mesenteric blood
flow. Thus, adequate restoration of portal blood flow to the liver graft is a
major concern when trying to achieve successful liver transplantation in patients
with PVT. This letter describes the surgical view point of PVT in liver
transplantation.
PMID- 26421020
TI - Ideal Experimental Rat Models for Liver Diseases.
AB - There are many limitations for conducting liver disease research in human beings
due to the high cost and potential ethical issues. For this reason, conducting a
study that is difficult to perform in humans using appropriate animal models, can
be beneficial in ascertaining the pathological physiology, and in developing new
treatment modalities. However, it is difficult to determine the appropriate
animal model which is suitable for research purposes, since every patient has
different and diverse clinical symptoms, adverse reactions, and complications due
to the pathological physiology. Also, it is not easy to reproduce identically
various clinical situations in animal models. Recently, the Guide for the Care
and Use of Laboratory Animals has tightened up the regulations, and therefore it
is advisable to select the appropriate animals and decide upon the appropriate
quantities through scientific and systemic considerations before conducting
animal testing. Therefore, in this review article the authors examined various
white rat animal testing models and determined the appropriate usable rat model,
and the pros and cons of its application in liver disease research. The authors
believe that this review will be beneficial in selecting proper laboratory
animals for research purposes.
PMID- 26421022
TI - Risk Factors for Intrahepatic Recurrence after Resection of Hepatocellular
Carcinomas in Patients with Hepatitis B Virus Infection.
AB - PURPOSE: Although surgical resection offers patients with HCC the chance of a
cure, the post-resection tumor recurrence rate is high, with reported cumulative
5-year tumor recurrence rates ranging from 40 to 70%. The objective of this study
was to investigate risk factors for intrahepatic recurrence after resection of
hepatocellular carcinoma, especially in patients with hepatitis B virus
infection. METHODS: Between January 1999 and December 2003, 59 patients in our
Hospital with hepatitis B virus infection underwent liver resection for
hepatocellular carcinoma. Clinical, biological, and histopathological
characteristics of these patients were collected and tested for their prognostic
significance using a Chi-square test and a Student's t-test. Time to recurrence
and survival rate were analyzed by the Kaplan-Meier method. RESULTS: Of the 59
patients who underwent liver resection, 24 (41%) experienced intrahepatic
recurrence. The 1-, 3-, and 5-year overall survival rates of total enrolled
patients were 83%, 63%, and 42%, respectively. The 1-, 3-, and 5-year overall
survival rates after recurrence were 87%, 52%, and 20%, respectively. The risk
factors for early recurrence were elevated serum aspartate aminotransferase (AST)
level (p=0.044) and larger tumor size (p=0.049). For late recurrence, greater
tumor size (p=0.039) was the only risk factor. CONCLUSION: Tumor size and serum
aspartate aminotransferase are risk factors of intrahepatic recurrence after
resection of HCC in patients with chronic hepatitis B virus infection. This
finding indicates that patients who have these risk factors should be under more
careful supervision and have more aggressive follow-up.
PMID- 26421023
TI - Outcome of Hepatectomy for Huge Hepatocellular Carcinoma.
AB - PURPOSE: In spite of the recent improved results of hepatectomy for huge
hepatocellular carcinomas (HCC), the prognosis of patients with huge HCCs is
still poor compared to that of patients with small HCCs. This study was performed
to compare the results of hepatectomy between patients with huge HCCs and those
with small HCCs, to identify the prognostic factors in patients with huge HCCs,
and to determine the preoperative selection criteria. METHODS: We retrospectively
analyzed 51 patients who underwent hepatectomy, between July 1994 and February
2009 at Dankook University Hospital. Patients with HCC>=10 cm were classified in
large (L) group and others were classified in small (S) group. The
clinicopathological features, operative procedures, and postoperative outcome
were compared between both groups and various prognostic factors were
investigated in group L. RESULTS: Eleven patients were classified in group L.
Tumor size, vascular invasion, and tumor stage were higher in group L.
Postoperative morbidity was higher in group L, but mortality was not different
between the groups. Disease-free survivals were significantly lower in group L
than in group S (36.4%, and 24.2% vs. 72.0%, and 44.0% for 1- and 3-year), but
overall survival rates were similar in both groups (45.5%, and 15.2% in group L
vs. 60.3%, and 41.3% in group S for 3- and 5-year). Presence of satellite nodules
was the only prognostic factor in multivariate analysis after surgery for huge
HCC. CONCLUSION: Regardless of tumor size, huge HCCs deserve consideration for
surgery in patients with preserved liver function. Furthermore, the effect of
surgery could be maximized with appropriate selection criteria, such as huge HCC
without satellite nodules.
PMID- 26421024
TI - Anatomical Variation of the Glissonean Pedicle of the Right Liver.
AB - PURPOSE: Many studies have been conducted to date regarding whether the right
hepatic vein is the accurate border that divides the anterior and posterior
section of the right liver. It has been reported that the Glisson pedicle of the
right liver may be an anatomical variation that does not have a consistent
morphology. We analyzed the relationship between the true borders of the anterior
and posterior sections, and the right hepatic vein, based on cadaver dissection
and MD-CT image analysis of the anatomical variation of the Glisson pedicle of
the right liver. METHODS: Sixteen cadaver livers were available for dissection
from the Department of Anatomy, and pre-operative MD-CTs of 20 donor livers who
underwent living donor liver transplantation prior to December 2009, were
obtained. We analyzed the 3D-relationship between the branches of the Glisson
pedicles and the right hepatic vein of the right liver. They were divided into 3
groups according to the sliding pattern of the branches of the Glisson pedicle
origin. When all segmental branches of the anterior pedicle arise from the main
trunk of the anterior pedicle and all branches of posterior pedicle arise from
the main trunk of posterior pedicle, it was designated as Group A (Normal Group).
When a portion of the segmental branches of the anterior pedicle arises from the
main trunk of the posterior pedicle, it was designated as Group B (Posterior
dominant group). When a portion of the branches of the posterior pedicle arises
from the main trunk of the anterior pedicle, it was designated as Group C
(Anterior dominant group). RESULTS: Among the 16 cadaver liver dissections, 6
cases were in Group A, 5 in Group B, and 3 in Group C. Two cases were excluded
from the study because the inferior right hepatic vein was the main draining vein
of the right liver. The analysis of preoperative MD-CT of the 20 donor livers
showed that there were 13, 4, and 3 patients in Groups A, B, and C, respectively.
CONCLUSION: According to Couinaud's theory of anatomy, the right hepatic vein
serves as the border between the anterior and posterior sections of the right
liver. But, due to the frequent anatomical variations, an adequate understanding
of the anatomical variations of the right Glisson pedicle should be necessary for
liver surgery.
PMID- 26421025
TI - Effect of Liver Cell Transplantation on Acute Hepatic Failure Induced by Massive
Liver Resection in the Rat.
AB - PURPOSE: This study is designed to ascertain the most effective quantity and
injection route of hepatocytes in an acute liver failure model induced by massive
liver resection in rats. METHODS: Rats weighing 450 to 650 gm underwent partial
hepatectomy that was 80% of their liver weight, resulting in acute liver failure.
Hepatocytes were obtained by perfusing collagenase (Wako, Japan) solution through
portal vein into liver of the allogenic rat. These hepatocytes were injected into
different places with different dosage. The experimental groups were divided into
the Control group, Splenic group I (2*10(6) cells into splenic capsule), Splenic
group II (2*10(7) cells into splenic capsule), Portal vein group (2*10(7) cells
into portal vein), Subperitoneal group (2*10(7) cells into subperitoneum). The
experimental animals were observed carefully for 5 days for assessment of
survival and regeneration of liver. Liver function tests including serum alanine
aminotransferase (ALT), total bilirubin, gamma-glutamyl transferase (gamma-GTP)
on postoperative 1, 2, 3, 5th days and histologic examinations of specimens
obtained from each respective groups on postoperative 5th day were performed.
RESULTS: Serum ALT level on postoperative day 1 peaked and then gradually
normalized showing statistical significance (p=0.035). Study groups showing
statistically significant difference under repeated anova analysis were between
the Splenic group II and Control (p=0.035), and between the Splenic group II and
Portal vein group (p=0.001) with respect to serum ALT levels. Also, progression
of each study group showed statistical significance. (p=0.02). Serum total
bilirubin and r-GTP did not show any significant difference. CONCLUSION:
Hepatocyte transplantation of 2*10(7) cells into spleen showed the best results
in the acute hepatic failure rat.
PMID- 26421026
TI - Comparison of Bile Drainage Methods after Laparoscopic CBD Exploration.
AB - PURPOSE: T-tube is a major procedure that prevents complication by biliary
decompression, but which is accompanied by complications. Therefore, several
procedures such as ENBD, PTBD, and antegrade biliary stent have been attempted,
but with controversies as to which procedure is superior. Also, there are no
standard procedures after laparoscopic CBD exploration. We performed this study
to ascertain the most appropriate biliary drainage procedure after laparoscopic
CBD exploration. METHODS: From March 2001 to December 2009, 121 patients who
underwent Laparoscopic CBD exploration in Gunyang University were included for
retrospective analysis. The patients were divided to 4 groups according to type
of procedure, and we compared clinical parameters including age and gender,
operation time, hospital stay, start of post-operative diet, and complications.
RESULTS: There was no difference in age, gender, mean operation time,
postoperative diet between the 4 groups. Hospital stay in the Stent group was
shorter than T-tube group. There were 10 (7%) complications that occurred. Two 2
occurred in the T-tube, 3 in PTBD, and 5 in the Antegrade stent group. There were
more complications in Stent group but no significant statistical difference. In 5
cases with remnant CBD stone, a total of 4 (3 PTBD, 1 Stent) was performed by
endoscopic CBD stone removal. One T-tube case was removed easily by
choledochoscopy through the T-tube. Three migrated and the impacted stents were
removed by additional endoscopy. Perioperative biliary leakage (1) and
peritonitis (1) post t-tube removal were resolved by conservative treatment.
CONCLUSION: T-tube appears to be an appropriate method to patients who are
suspected to have remnant CBD stones. Multiple procedures may be performed on a
case by case basis such as performing PTBD first in a suspected cholangitis
patient.
PMID- 26421027
TI - Pancreatic Diabetes after Distal Pancreatectomy: Incidence Rate and Risk Factors.
AB - PURPOSE: Pancreatectomy can impair production of endocrine and exocrine hormones.
In this study, we evaluated: 1) the incidence rate of diabetes in patients
undergoing distal pancreatectomy; 2) the correlation between the occurrence of
pancreatic diabetes and the extent of the resected pancreas; and 3) factors
associated with the development of pancreatic diabetes. METHODS: We
retrospectively reviewed the cases of 26 patients who could be compared in
abdominal computed tomography before and after distal pancreatectomy for benign
or malignant lesions between January, 1999 to June, 2010. RESULTS: The incidence
of pancreatic diabetes was 19.2%. Obese patients (BMI>25.0 kg/m(2)) had a higher
incidence (p=0.029) of pancreatic diabetes after distal pancreatectomy than non
obese patients. The diabetes group had larger volumes of resected pancreas, but
the difference was not statistically significant (p=0.105). CONCLUSION: Several
factors may be associated with the development of pancreatic diabetes after
distal pancreatectomy. It is necessary to closely follow-up development of
pancreatic diabetes regardless of the extent of resection.
PMID- 26421028
TI - Fat Tissue Infiltration into the Pancreas Parenchyme and Its Effect on the Result
of Surgery.
AB - PURPOSE: In Korea, there are few reports regarding the infiltration of fat tissue
in pancreatic parenchyma in surgically resected organs. It is necessary to
ascertain the correlation between the presence of fat tissue in the resection
margin of the pancreas and the surgery outcome. METHODS: Fifty four patients who
underwent pancreatic resection from Jan. 2007 to Nov. 2008 were enrolled in this
study. Pathologic examination was performed to determine the presence of fat
tissue in resected pancreatic parenchyma. Statistical correlation between the
presence of fat tissue with clinical parameters and postoperative complication
rates was analyzed. RESULTS: Among the specimens of all fifty four patients, fat
tissue was found in 32 specimens of patients (59.3%). Female gender and patients
whose body mass index exceeded 24 kg/m(2) were statistically correlated with the
presence of the fat tissue in pancreatic parenchyma. There was no statistical
relationship between infiltration of fat tissue with postoperative complications.
CONCLUSION: This study may serve as the base data for study in radiological
imaging in detecting pancreatic tissue. A further larger scaled study is needed
to validate the result of this study.
PMID- 26421029
TI - Serous Cystic Neoplasm: Do We Have to Wait Till It Causes Trouble?
AB - Serous cystic neoplasm (SCN) of the pancreas is considered a benign tumor with
almost no malignant potential. Most surgeons agree that asymptomatic SCN requires
only regular observation. However, several complexities and interference with
organ preservation during the operation, may develop when a huge symptomatic
tumor is treated with surgery. So, the purpose of this study is to develop a
potential management plan based on a literature review and by describing three
recent cases of SCN of the pancreas. We suggest that SCNs be responded to with a
timely and appropriate surgical intervention - before they require clinical
attention.
PMID- 26421031
TI - Scoring of prognostic factors that influence long-term survival in patients with
hepatic metastasis of colorectal cancer.
AB - BACKGROUNDS/AIMS: To find independent predictors that affect the survival in
patients with hepatic metastasis of colorectal cancer after surgery and to devise
a risk scoring system. METHODS: Among 150 patients who underwent hepatic
resection after diagnosis of colorectal cancer with hepatic metastasis between
March 1994 and February 2009, we analyzed clinical, pathologic and outcome data
retrospectively. RESULTS: The 1-year survival rate was 83%, and the 5-year
survival rate was 35%. Nine factors were found to be independent predictors of
adverse outcome by univariate analysis: stage of primary tumor, CA19-9 >36 U/ml,
extrahepatic disease, distribution of the hepatic tumor, number of hepatic tumors
>3, largest hepatic tumor >5 cm, total size >10 cm, CEA >10 ng/ml, and
metachronous cancer. The last two of these criteria were also significant risk
factors on multivariate analysis. When these criteria were used as a risk scoring
system, assigning one point for each criterion and dividing the cases into A, B
and C groups, the total score was highly predictive of outcomes (p<0.001). No
patients in group C (6 to 9 points) were long-term survivors. CONCLUSIONS: Long
term outcome can be predicted from nine criteria that are readily available for
all patients. Patients meeting up to two criteria (group A) are more likely to
have a favorable outcome compared to the three or over (groups B and C). This
scoring system may offer an easy, rapid, and reliable prognostic indicator of
survival outcome after hepatic resection in patients with hepatic metastasis from
colorectal cancer.
PMID- 26421030
TI - Selection of surgical treatment types for intrahepatic duct stones.
AB - BACKGROUNDS/AIMS: Complete elimination of intrahepatic duct (IHD) stones is
difficult and IHD stone disease is frequently associated with various
complications, recurrence and sometimes cholangiocarcinoma. Therefore, we
analyzed the long-term surgical results and evaluated the management currently
considered appropriate. METHODS: Overall 110 patients who had been diagnosed with
benign IHD stone disease and who underwent surgical treatment were enrolled in
this study. The patients were categorized into three groups according to the type
of surgery performed; liver resection (LR) group, intrahepatic duct exploration
(IHDE) group and hepaticoenterostomy (HE) group. We compared and analyzed the
results of these three groups. RESULTS: The number of cases in the LR group, IHDE
group and HE group were 77, 25 and 8 respectively. The LR group required a longer
operation time (p=0.000), more frequent transfusion (p=0.028) and had higher
morbidity (p=0.049). However, the LR group had a higher clearance rate (90.9%)
(p=0.000) than the other groups. In addition, there were a total of 22 cases of
IHD stone recurrence during the follow-up, but there was no statistically
significant difference among the three groups. The location of IHD stones was
related to a risk factor for incomplete stone removal, but not for recurrence.
CONCLUSIONS: The fundamental principle for the treatment of IHD stone disease
should be liver resection. However, it can lead to a longer operative time and
higher rate of complications than the other procedures. There is also no
difference in the IHD stone recurrence rate among the procedures. Therefore,
these alternative and minor procedures could also be taken into account for
patients with poor preoperative condition.
PMID- 26421032
TI - Treatment outcomes and prognostic factors of gallbladder cancer patients after
postoperative radiation therapy.
AB - BACKGROUNDS/AIMS: To investigate survival rates and prognostic factors of
patients with gallbladder cancer who were treated with surgery and postoperative
radiation therapy. METHODS: Seventeen gallbladder cancer patients who received
surgery and postoperative radiotherapy from October 1989 to April 1998 were
included in this retrospective study. Five patients had stage II, 8 patients had
stage III, and 4 patients had stage IV disease according to the 1997 American
Joint Committee on Cancer (AJCC) staging. All patients received >=40 Gy of
postoperative radiotherapy with a daily dose of 2.0 Gy/fraction and 15 patients
received concurrent chemotherapy. An analysis was performed for the end-points of
overall and disease-free survival. RESULTS: Of the 17 patients, 13 had no
residual disease (R0), 1 had microscopic residual disease (R1), and 3 had
macroscopic residual disease (R2) after surgery. Among patients with no residual
disease, 4 had locoregional recurrences during the follow-up period. One patient
with microscopic residual disease had local recurrence. The 5-year overall
survival rate was 38.2%. The median overall survival time was 21 months and the
median disease-free survival time was 12 months. Old age (>=60 years old), female
gender, a high pathological stage (>=IVA), and the presence of residual disease
after surgery were significant prognostic factors for disease-free survival.
CONCLUSIONS: Despite a high proportion of patients with advanced disease and
macroscopic residual disease, the prognosis of gallbladder patients who had
postoperative radiotherapy is encouraging. Additional investigation to improve
the loco-regional control of gallbladder cancer patients with adverse prognostic
factors is warranted.
PMID- 26421033
TI - Clinical comparison of choledochal cysts between children and adults.
AB - BACKGROUNDS/AIMS: Choledochal cyst of the bile duct is characterized by cystic
dilatation of the intra- or extrahepatic bile ducts. It is a relatively uncommon
disease and there is still much controversy regarding its etiology as being
congenital or acquired. METHODS: The medical records of 60 patients who underwent
surgical treatments for choledochal cyst between April 1995 and April 2009 at the
Gachon University Gil Hospital were reviewed retrospectively. To compare the
clinical characteristics, patients under 19 years of age were grouped into
children and the others were grouped into adults. RESULTS: Of the overall 60
patients, 24 were grouped into children and 36 were grouped into adults. Female
predominance was common in both groups (M : F=1 : 6.5). The most common clinical
symptom was abdominal pain (73.3%) in both groups. Children had remarkable
jaundice (33.3% vs. 0%) and gastrointestinal symptoms including nausea and
vomiting. Fever and chills were more common in children because of the associated
complications of cholangitis. According to the Todani classification, type I was
the most common form of choledochal cyst in both groups, and type IVa was
significantly more common in children than adults (45.3% vs. 16.7%). Thirty
patients (50%) had anomalous pancreaticobiliary ductal union which was confirmed
by preoperative imaging studies or intraoperative cholangiography. All patients
except for one child underwent cyst excision with hepaticojejunostomy.
CONCLUSION: There was no significant difference in the clinical characteristics
of choledochal cysts between children and adults. However, combined diseases
especially bile duct malignancy were common in aged patients, early detection and
more aggressive surgery is necessary for patients with choledochal cysts.
PMID- 26421034
TI - Risk factors for the clinical course of cholecystitis in patients who undergo
cholecystectomy.
AB - BACKGROUNDS/AIMS: The aims of this study were to evaluate risk factors for acute
cholecystitis that have been previously acknowledged and to evaluate several co
morbidities, such as hypertension, diabetes mellitus, cardiovascular disease,
cerebrovascular accident and end-stage renal disease for which the prevalence
rate has increased in the elderly. METHODS: We retrospectively reviewed 611
patients who underwent laparoscopic or open cholecystectomy for cholecystitis
between January 2005 and January 2010. The relationships between the clinical
outcomes and the clinico-demographic factors were analyzed by univariate and
multivariate analyses. RESULTS: The diagnoses of the 611 patients who underwent
laparoscopic cholecystectomy were acute cholecystitis (n=258; 42.2%) and chronic
cholecystitis (n=353; 57.8%). Male gender (p<0.000), age >50 (p<0.000), fever
(p<0.000), leukocytosis (p<0.000), AST elevation (p=0.009), alkaline phosphatase
elevation (p<0.000) and an elevation of total bilirubin (p<0.000) were identified
as risk factors for acute cholecystitis. The presence of diabetes mellitus
(p=0.002) and hypertension (p=0.019) may be risk factors for acute cholecystitis.
CONCLUSIONS: For patients with risk factors for acute cholecystitis, early
management, that is, early checkup and diagnosis following early cholecystectomy,
is recommended before the disease progresses to an acute form of cholecystitis.
PMID- 26421035
TI - Adenocarcinoma of the ampulla of Vater: predictors of survival and recurrence
after curative radical resection.
AB - BACKGROUNDS/AIMS: Because of low incidence rates, there have been few reports on
the patterns of and risk factors for recurrence after curative resection of the
ampulla of Vater (AoV) cancer. The aim of this study was to characterize patterns
of recurrence and to evaluate risk factors affecting survival rates and
recurrence after curative resection. METHODS: Medical records of 181 patients who
had undergone pancreaticoduodenectomy with curative intent for AoV adenocarcinoma
between December 1994 and March 2010 at Samsung Medical Center were
retrospectively reviewed. Factors influencing on overall survival rate,
recurrence rates, and recurrence patterns were analyzed. RESULTS: Lymph node
metastases and high preoperative serum carcinoembryonic antigen (CEA) level >5
ng/ml were identified as independent factors affecting overall survival (p=0.006,
p<0.001, respectively). Among the 181 patients, 69 developed local or distant
recurrence within 3 years after curative resection. Lymph node metastasis,
preoperative serum CEA level >5 ng/ml, and total bilirubin level >1.5 mg/dl were
identified as independent prognostic factors of recurrence after curative
resection (p=0.008, p<0.001, p=0.003, respectively). CONCLUSIONS: AoV
adenocarcinoma has a better prognosis than other periampullary carcinomas, but
still has a high recurrence rate, especially during the first three years after
curative radical resection. Therefore, careful follow-up is needed during the
first 3 years, especially for the higher risk group. Further study of adjuvant
therapy to decrease recurrence after curative resection is now warranted.
PMID- 26421036
TI - Solitary percutaneous transhepatic biliary drainage tract metastasis after
curative resection of perihilar cholangiocarcinoma: report of a case.
AB - Percutaneous transhepatic biliary drainage (PTBD) has been widely used, but it
has a potential risk of tumor spread along the catheter tract. We herein present
a case of solitary PTBD tract metastasis after curative resection of perihilar
cholangiocarcinoma. Initially, endoscopic nasobiliary drainage was done on a 65
year-old female patient, but the cholangitis did not resolve. Thus a PTBD
catheter was inserted into the right posterior duct. Right portal vein
embolization was also performed. Curative surgery including right hepatectomy and
bile duct resection was performed 16 days after PTBD. After 12 months, serum CA19
9 had increased gradually without any symptoms. Finally, a small right pleural
metastasis was found through strict tumor surveillance for 6 months.
Chemoradiation therapy was performed, but there was no response to treatment. As
the tumor progressed, she complained of severe dyspnea and finally died from
tumor dissemination to the chest and bones 18 months after the first detection of
PTBD tract recurrence and 36 months after surgery. No intra-abdominal recurrence
was found until the terminal stage. This PTBD tract recurrence was attributed to
the PTBD even though it was in place for only 16 days. Although such recurrence
is rare, its risk should be taken into account during follow-up of patients who
have received PTBD before.
PMID- 26421037
TI - Cavo-caval intervention stent insertion after deceased-donor liver
transplantation using side-to-side piggyback technique: report of a case.
AB - Liver transplantation with preservation of the recipient vena cava (piggyback
technique) has been performed as an alternative to the conventional method.
Outflow disturbance or obstruction of the vena cava in the early period after
liver transplantation is associated with high morbidity and mortality. We used
side-to-side cavo-caval anastomosis (modified piggyback technique) in a deceased
donor liver transplantation (DDLT) for venous outflow reconstruction. On
postoperative day 9, the patient developed abdominal discomfort, and abnormal
liver function showing serum total bilirubin of 6.2 mg/dl and serum AST/ALT of
297/597 IU/L. Doppler ultrasound showed mono-phasic wave forms of the hepatic
vein. Computed tomography showed focal narrowing of 9.5 mm*12 mm in diameter at
the cavo-caval anastomosis site. Liver biopsy was showed that there was no
evidence of acute allograft rejection. Direct venogram showed stenosis of the
cavo-caval anastomosis with a pressure gradient of 12 mmHg. An interventional
stent was inserted in the stenotic site of the inferior vena cava, and the
pressure gradient decreased to 2 mmHg. He was discharged from hospital on
postoperative day 23 without any other complications. Herein we report a case of
deceased-donor liver transplantation using the modified piggyback technique, who
received an inferior vena cava stent due to stricture of the reconstructed
orifice of the vena cava.
PMID- 26421038
TI - Therapeutic induction of hepatic atrophy for isolated injury of the right
posterior sectoral duct following laparoscopic cholecystectomy.
AB - Laparoscopic cholecystectomy has resulted in various bile duct injuries.
Treatment of these injuries is usually difficult and often leads to an
intractable clinical course. We herein present a case of isolated right anterior
sector (RAS) duct injury induced by laparoscopic cholecystectomy. The bile duct
injury was successfully treated by hepatic atrophy induction. Imaging studies
revealed that the RAS duct was severed, probably due to rare anatomical
variations. Considering the difficulty in surgical reconstruction, atrophy
induction of the involved hepatic parenchyma was attempted. This treatment
consisted of embolization of the RAS portal branch to inhibit bile production,
induction of heavy adhesion at the bile leak site to ensure percutaneous pigtail
clamping, and sequential clamping and removal of pigtail catheters. This
procedure took 3 months prior to pigtail catheter removal. She was free from
other complications during the first 12 months and to date. She will be followed
up for 5 years overall including surveillance for hepatobiliary complications.
Although this therapeutic induction of atrophy approach is not universally
applicable, it can be considered to be a feasible option in unique situations
such as this one.
PMID- 26421039
TI - Partial gastric outlet obstruction caused by a huge submucosal tumor originating
in the heterotopic pancreas.
AB - A 21-year-old woman presented gastrointestinal manifestation showing intermittent
abdominal pain, nausea, and vomiting. An upper endoscopic examination showed
round, elevated mucosa at the antrum of the stomach anterior wall. After CT
scanning, a huge degenerated gastrointestinal stromal tumor was suspected.
Subtotal gastrectomy with Billroth II anastomosis was performed. Histologically,
pseudocystic degeneration of the heterotopic pancreas was confirmed. The patient
showed eventful postoperative course except temporary dilated gastric emptying.
The patient is doing well without any abnormal symptom at 8-month follow-up. This
report is a rare case of gastric outlet obstruction caused by a pseudocyst
originating from a heterotopic pancreas in the gastric antrum.
PMID- 26421040
TI - Long-term outcome after liver resection and clinicopathological features in
patients with small hepatocellular carcinoma.
AB - BACKGROUNDS/AIMS: Surveillance programs and imaging modality developments have
increased the detection rate of small hepatocellular carcinoma (HCC). In
particular, liver transplantation produces good results and is now regarded an
alternative to liver resection. However, optimal treatment for small HCC is still
debated, and thus, the authors designed this study to document
clinicopathological characteristics, to identify the prognostic factors of small
HCC, and to determine the effectiveness of surgery. METHODS: A total of 507
patients underwent curative liver resection for HCC between January 1996 and
August 2006 in our institution. One hundred and thirty four of these patients
with a single HCC of less than 3 cm and no gross vascular invasion were enrolled.
RESULTS: Major resection was performed in 32 (23.9%) patients; there was no
postoperative mortality. Fifty-eight (43.3%) patients experienced recurrence, 53
developed intrahepatic recurrence alone, and 50 (94.3%) of 53 had tumors within
the Milan criteria. Five-year disease-free and overall survival rates were 51.0%
and 77.3%, respectively. Microscopic vascular invasion, positivity for hepatitis
B surface antigen or antibody to hepatitis C, and an indocyanine green retention
test at 15 minutes of more than 10% were found to be significantly correlated
with disease-free overall survival. A platelet count of less than 100,000/mm(3)
was the only independent prognostic factors of overall survival identified.
CONCLUSIONS: This study showed favorable outcome comparable to the survival after
liver transplantation, thus that liver resection appears to be the primary
treatment option for small HCC, even in cases with poor prognostic factors.
PMID- 26421041
TI - Is neoadjuvant chemotherapy necessary for patients with initially resectable
colorectal liver metastases in the era of effective chemotherapy?
AB - BACKGROUNDS/AIMS: Hepatic resection has only guaranteed long-term survival in
patients with colorectal liver metastasis (CRLM) even in the era of effective
chemotherapy. The definite role of neoadjuvant chemotherapy (NCT) is to improve
outcomes of unresectable CRLMs, but it its role has not been defined for
initially resectable CRLMs (IR-CRLMs). METHODS: We reviewed the medical records
of 226 patients, who had been diagnosed and treated for IR-CRLM between 2003 and
2008; the patients had the following pathologies: 10% had more than 4 nodules,
11% had tumors larger than 5 cm, and 61% had synchronous CRMLs. Among these
patients, 20 patients (Group Y) were treated with NCT, and 206 (Group N) did not
receive NCT according to their physician's preference. The median follow-up time
was 34.1 months. RESULTS: The initial surgical plans were changed after NCT to
further resection in 20% and to limited resection in 10% of 20 patients.
Complication rates of Groups Y (30%) were indifferent from Group N (23%)
(p=0.233), but intraoperative transfusions were more frequent in Group N (15%)
than in Group Y (5%) (p=0.006). There was one case of hospital mortality (0.44%).
Disease-free survival rates in Groups Y and N were 23% and 39%, respectively, and
patient survival rates were 42% and 66% (p>0.05). By multivariate analysis, old
age (>=60 years), differentiation of primary tumor (poorly/mucinous), resection
margin involvement, and no adjuvant chemotherapy were associated with poor
patient survival; the number of CRLMs (>=4) was associated with poor disease-free
survival. CONCLUSIONS: NCT had neither a positive impact nor a negative impact on
survival, even with intraoperative transfusion, as observed on operative outcomes
for patients with IR-CRLM. Further study is required to elucidate the role of NCT
for treatment of patient with IR-CRLMs.
PMID- 26421042
TI - What we learned from difficult hepatectomies in patients with advanced hepatic
malignancy.
AB - BACKGROUNDS/AIMS: By reviewing difficult resections for advanced hepatic
malignancies, we discuss the effectiveness and extended indications for
hepatectomy in such patients. METHODS: We reviewed 7 patients who underwent
extensive surgery between July 2008 and March 2011 for advanced hepatic
malignancies. They had stage IV disease, except for in one case that was a stage
IIIC (T4N0M0) hepatocellular carcinoma (HCC). RESULTS: Patient 1 with
intrahepatic cholangiocarcinoma (IHCC) underwent right hemihepatectomy and
resection of the bile duct and left portal vein. At 39 months after surgery, she
had no recurrence or metastasis. Patient 2 with HCC underwent palliative right
trisectionectomy. At 38 months after surgery, he is alive despite residual
pulmonary metastases. Patient 3 with HCC invading the hepatic vein and diaphragm
underwent right trisectionectomy and caval venoplasty. At 12 months after
surgery, he had no recurrence or metastasis. Patient 4, who had 2 large HCCs and
pulmonary thromboembolism, underwent a right trisectionectomy. At 7 months after
surgery, he had no evidence of recurred HCC. Patient 5, who had IHCC invading her
inferior vena cava and main portal vein, underwent preoperative radiotherapy,
left hemihepatectomy, and caval resection. At 20 months after surgery, she is
well despite a caval thrombus. Patient 6 and 7 underwent repeated surgery due to
a recurred IHCC and metastatic colon cancer, respectively. In addition, they are
alive during each 20 and 17 months after surgery. CONCLUSIONS: Despite
macroscopic extrahepatic metastases or major vessel involvement, extensive
surgery for advanced hepatic malignancy may result in relatively favorable
outcomes and be important modality for improving of survival in such patients.
PMID- 26421043
TI - Efficacy and feasibility of laparoscopic subtotal cholecystectomy for acute
cholecystitis.
AB - BACKGROUNDS/AIMS: For patients with acute cholecystitis, conversion from
laparoscopic cholecystectomy to open surgery is not uncommon due to possibilities
of serious hemorrhage at the liver bed and bile duct injury. Recent studies
reported successful laparoscopic subtotal cholecystectomy for acute
cholecystitis. The purpose of this study was to determine the efficacy and
feasibility of such an operation based on the experience of surgeons at our
facility. METHODS: In this study, we enrolled 144 patients who had received
either laparoscopic subtotal cholecystectomy (LSC), laparoscopic cholecystectomy
(LC), or open cholecystectomy (OC) for acute cholecystitis from January 2004 to
December 2009 at the Department of Surgery of our hospital. Their symptoms,
signs, operative findings, pathologic results and postoperative results were
compared and analyzed. RESULTS: There were 26 patients in the LSC group 80 in the
LC group and 38 in the OC group. There were no differences in mean age, sex, and
symptoms of acute cholecystitis. The LSC group showed higher CRP levels (p<0.001)
and a higher grade according to the Tokyo criteria (p=0.001). The mean operative
time was 115.6 minutes and mean blood loss was 158.9 ml without intra-operative
or postoperative transfusion. There weren't any bile duct injuries during the
operation. No group suffered bile leakage. Drains were removed 3.3 days after the
operation in the LC group, the shortest time compared to the other groups
(p<0.001). LC and LSC groups demonstrated shorter postoperative hospital days and
time to diet resumption than the OC group (p<0.001). CONCLUSIONS: LSC appears to
be a safe and effective treatment in cases of severe acute cholecystitis that
require consideration of conversion to open surgery.
PMID- 26421044
TI - Effectiveness of external drainage of the bile duct in pancreaticoduodenectomy: a
single surgeon's experience.
AB - BACKGROUNDS/AIMS: The rates of surgery-related complications during and after
pancreaticoduodenectomy (PD) remain very high, reaching up to 41%. They were
primarily caused by leakage of pancreatic juice. We evaluated the effectiveness
of external drainage of the bile duct using a pigtail drain to prevent pancreatic
leakage in patients undergoing PD. METHODS: We evaluated 79 patients who
underwent PD using a single-layer continuous suture between the pancreatic
parenchyma and jejunum after duct-to-mucosa anastomosis by a single surgeon from
April 2005 to December 2008. Of the 79, 44 underwent external drainage (ED) of
the bile duct using a pigtail drain, performed in the intraoperative field via a
retrograde transhepatic approach, whereas 35 did not undergo ED. RESULTS: Age,
sex distribution, number of total complications, pancreatic duct size, pancreatic
texture and duration of hospital stay did not differ between patients who did and
did not undergo ED. In groups with or without ED, 0 and 4 patients, respectively,
showed leakage of pancreatic juice and the difference was statistically
significant (p=0.02). CONCLUSIONS: The fact that none of the patients who
underwent external drainage experienced pancreatic leakage, suggests that
external drainage of the bile duct with a pigtail drain to decompress the jejunum
and to drain pancreatic and bile juice is useful in preventing the complications
of pancreatic leakage.
PMID- 26421046
TI - Complication analysis of distal pancreatectomy based on early personal
experience.
AB - BACKGROUNDS/AIMS: The objective of this study was to evaluate the relationship
between initial personal experiences with distal pancreatectomy and perioperative
risk factors, outcomes, and management of pancreatic fistulas. METHODS: Between
May, 2007 and May, 2010, a total of 28 patients who had undergone elective distal
pancreatectomy were evaluated for this study. Perioperative factors and the
occurrence of pancreatic fistula were analyzed on the basis of International
Study Group of Pancreatic Fistula (ISGPF) criteria. RESULTS: There were sixteen
cases of benign neoplasms and twelve cases of malignant tumors. The remnant
pancreas was manually sutured with ligation of the pancreatic duct (n=14), auto
suture stapling along with manual sutures (n=12), or stapling alone (n=2).
According to the ISGPF classification, morbidity and mortality associated with
pancreatic fistulas was 42.9% (n=12) and 0%, respectively. These pancreatic
fistulae were classified as grade A in 8 cases (28.6%), grade B in 3 cases
(10.7%), and grade C in one case (3.6%). All patients with pancreatic fistula
were treated conservatively. CONCLUSIONS: Perioperative factors do not affect the
risk of pancreatic fistula. Adequate drainage is the most effective method for
management of a pancreatic fistula after distal pancreatectomy.
PMID- 26421045
TI - Predictive factors for invasive intraductal papillary mucinous neoplasm of the
pancreas.
AB - BACKGROUNDS/AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas
has malignant potential. Predicting invasive IPMN has proven difficult and
controversial. We tried to identify predictive factors for invasive IPMN.
METHODS: Thirty six patients underwent resection for IPMN from February 2001 to
July 2011. Clinicopathological features including demographic, imaging,
microscopic, and serological findings were retrospectively reviewed. Receiver
operating characteristic (ROC) curve analysis was used to analyze sensitivity and
specificity of all possible cut-off values for the diameter of the main
pancreatic duct and mass size predicting invasive IPMN. Student t-test, chi
square test, and logistic regression were used for univariate and multivariate
analysis. RESULTS: The mean age was 63.5+/-8.4 years. Males were more commonly
affected (58.3% vs 41.7%). Pancreaticoduodenectomy was performed in 55.6% of
patients, distal pancreatectomy in 36.1%, and central pancreatic resection in
8.3%. Non-invasive IPMNs were present in 80.6% (n=29), whereas invasive IPMNs
were present in 19.4% (n=7). In univariate analysis, tumor location (p=0.036),
Kuroda classification (p=0.048), mural nodule (p=0.016), and main duct dilatation
(>=8 mm) (p=0.006) were statistically significant variables. ROC curve analysis
showed that a value of 8 mm for the main duct dilatation and a value of 35 mm for
the size of the mass lesion have 80% sensitivity and 75% specificity and 100%
sensitivity and 82.6% specificity, respectively. However, in multivariate
analysis, main ductal dilatation (>=8 mm) was identified to be the only
independent factor for invasive IPMN (p=0.049). CONCLUSIONS: Main duct dilatation
appears to be a useful indicator for predicting invasive IPMN.
PMID- 26421047
TI - The impact of old age on surgical outcomes after pancreaticoduodenectomy for
distal bile duct cancer.
AB - BACKGROUNDS/AIMS: To compare surgical results and survival of two groups of
patients, age >=70 vs. age <70, who underwent pancreaticoduodenectomy and to
identify the safety of this procedure for elderly patients for the treatment of
distal common bile duct (CBD) cancer. METHODS: Between January 2003 and December
2009, 55 patients who underwent pancreaticoduodenectomy for the treatment of
distal CBD cancer at Keimyung University Dong San Medical Center were enrolled in
our study. RESULTS: Of 55 patients, 28 were male and 27 female. Nineteen were
over 70 years old (older group) and 36 were below 70 years (younger group). The
mean ages of the two groups of patients were 73.5 years and 60.5 years
respectively. Although patients of the older group had significantly more
comorbid diseases, perioperative results including operation time, amount of
intraoperative bleeding, duration of postoperative hospital stay and
postoperative complications were not significantly different. A higher level
(more than 5 mg/dl) of preoperative initial bilirubin showed significant
correlations with operative morbidity by univariate analysis, and age was not an
independent risk factor of operative morbidity. Overall 5 year survival of older
and younger groups were 45.9% and 39.5% respectively (p=0.671) and disease-free 5
year survival were 31.7% and 31.1%, respectively (p=0.942). CONCLUSIONS: Surgical
outcomes of elderly patients were similar to those of younger patients, despite a
higher incidence of comorbid disease. This results shows that
pancreaticoduodenectomy can be applied safely to elderly patients.
PMID- 26421048
TI - Self-Care Practices for Common Colds by Primary Care Patients: Study Protocol of
a European Multicenter Survey-The COCO Study.
AB - Background. Self-care for common colds is frequent, yet little is known about the
spectrum, regional differences, and potential risks of self-care practices in
patients from various European regions. Methods/Design. We describe the study
protocol for a cross-sectional survey in 27 primary care centers from 14 European
countries. At all sites, 120 consecutive adult patients, who visit their general
practitioner for any reason, filled in a self-administered 27-item questionnaire.
This addresses patients' self-care practices for common colds. Separately, the
subjective level of discomfort when having a common cold, knowing about the
diseases' self-limited nature, and medical and sociodemographic data are
requested. Additionally, physicians are surveyed on their use of and
recommendations for self-care practices. We are interested in investigating which
self-care practices for common colds are used, whether the number of self-care
practices used is influenced by knowledge about the self-limited nature of the
disease, and the subjective level of discomfort when having a cold and to
identify potential adverse interactions with chronic physician-prescribed
medications. Further factors that will be considered are, for example,
demographic characteristics, chronic conditions, and sources of information for
self-care practices. All descriptive and analytical statistics will be performed
on the pooled dataset and stratified by country and site. Discussion. To our
knowledge, COCO is the first European survey on the use of self-care practices
for common colds. The study will provide new insight into patients' and general
practitioners' self-care measures for common colds across Europe.
PMID- 26421049
TI - Effect of Lepidium meyenii Walp. on Semen Parameters and Serum Hormone Levels in
Healthy Adult Men: A Double-Blind, Randomized, Placebo-Controlled Pilot Study.
AB - Background/Aims. Products of Lepidium meyenii Walp. (maca) are touted worldwide
as an alimentary supplement to enhance fertility and restore hormonal balance.
Enhancing properties of maca on semen parameters in animals were previously
reported by various authors, but we present to the best of our knowledge the
first double-blind, randomized, placebo-controlled pilot trial in men. The aim of
this study was to evaluate the effects of maca on semen parameters and serum
hormone levels in healthy adult men. Methods. A group of 20 volunteers aged 20-40
years was supplied by milled hypocotyl of maca or placebo (1.75 g/day) for 12
weeks. Negative controls of semen were compared to the samples after 6 and 12
weeks of maca administration; negative blood controls were compared to the
samples after 12 weeks of treatment. Results. Sperm concentration and motility
showed rising trends compared to placebo even though levels of hormones did not
change significantly after 12 weeks of trial. Conclusion. Our results indicate
that maca possesses fertility enhancing properties in men. As long as men prefer
to use alimentary supplement to enhance fertility rather than prescribed
medication or any medical intervention, it is worth continuing to assess its
possible benefits.
PMID- 26421050
TI - A Novel Pharmacological Method to Study the Chinese Medicinal Formula Hua-Zheng
Hui-Sheng-Dan.
AB - Objectives. Hua-Zheng-Hui-Sheng-Dan (HZHSD) was used as an experimental model to
explore research methods of large formulae in traditional Chinese medicine (TCM)
using current molecular biology approaches. Materials and Methods. The trypan
blue exclusion assay was used to determine cell viability and cell numbers. Flow
cytometry was used to assess cell cycle distribution and apoptosis. The
concentration of cyclin D1 was analyzed by enzyme-linked immunosorbent assay. The
median effect principle was used in drug combination studies. An orthogonal
experimental design was used to estimate the effects of each herb at different
concentrations. The HeLa xenograft mouse model was used to compare the antitumor
activity of drugs in vivo. Results. Among the 35 herbs that comprise HZHSD, Radix
Rehmanniae Preparata (RRP), Caesalpinia sappan (CS), Evodia rutaecarpa (ER),
Folium Artemisiae Argyi (FAA), Leonurus japonicus Houtt (LJH), Tumeric (Tu),
Radix Paeoniae Alba (RPA), and Trogopterus Dung (TD) effectively inhibited the
proliferation of HeLa and SKOV3 cells. Only RRR had an effect on HeLa and SKOV3
cell viability. According to the median effect principle, Angelica sinensis
(Oliv.) (AS), Tabanus (Ta), and Pollen Typhae (PT), which were proven to have a
significant synergistic inhibitory effect on the proliferation of HeLa cells,
were added to the original eight positive herbs. The combination of RPA and AS
had a synergistic effect on inducing cell cycle S phase arrest and decreasing
intracellular cyclin D1 in HeLa cells. By orthogonal experimental design, LJH and
Tu were considered unnecessary herbs. The small formula (SHZHSD) consisted of
RPA, AS, RRR, Ta., TD, PT, ER, CS, and FAA and was able to inhibit cell
proliferation and induce cell apoptosis. The antitumor effects of HZHSD and
SHZHSD were also compared in vivo. Conclusions. Through molecular biology
approaches both in vitro and in vivo, research into single drugs, and analysis
using the median effect principle and orthogonal experimental design, the small
formula (SHZHSD) was determined from the original formula (HZHSD). SHZHSD
exhibited superior antitumor activity compared with the original formula both in
vitro and in vivo.
PMID- 26421051
TI - Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of (60)Cobalt-Gamma
Irradiated Mice by Regulating Apoptosis and Tissue Regeneration.
AB - A single dose (30 mg/kg body weight) of standardized sea buckthorn leaf extract
(SBL-1), administered 30 min before whole body (60)Co-gamma-irradiation (lethal
dose, 10 Gy), protected >90% of mice population. The purpose of this study was to
investigate the mechanism of action of SBL-1 on jejunum and bone marrow, quantify
key bioactive compounds, and analyze chemical composition of SBL-1. Study with 9
week-old inbred male Swiss albino Strain 'A' mice demonstrated that SBL-1
treatment before (60)Co-gamma-irradiation (10 Gy) significantly (p < 0.05)
countered radiation induced decreases in jejunum crypts (1.27-fold), villi number
(1.41-fold), villus height (1.25-fold), villus cellularity (2.27-fold), cryptal
Paneth cells (1.89-fold), and Bcl2 level (1.54-fold). It countered radiation
induced increases in cryptal apoptotic cells (1.64-fold) and Bax levels (1.88
fold). It also countered radiation (2 Gy and 3 Gy) induced bone marrow apoptosis
(1.59-fold and 1.85-fold) and micronuclei frequency (1.72-fold and 2.6-fold). SBL
1 rendered radiation protection by promoting cryptal stem cells proliferation, by
regulating apoptosis, and by countering radiation induced chromosomal damage.
Quercetin, Ellagic acid, Gallic acid, high contents polyphenols, tannins, and
thiols detected in SBL-1 may have contributed to radiation protection by
neutralization of radiation induced oxidative species, supporting stem cell
proliferation and tissue regeneration.
PMID- 26421052
TI - Overcome Cancer Cell Drug Resistance Using Natural Products.
AB - Chemotherapy is one of the major treatment methods for cancer. However, failure
in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated
with drug resistance. Management of drug resistance is important towards
successful chemotherapy. There are many reports in the Chinese literature that
natural products can overcome cancer cell drug resistance, which deserve sharing
with scientific and industrial communities. We summarized the reports into four
categories: (1) in vitro studies using cell line models; (2) serum pharmacology;
(3) in vivo studies using animal models; and (4) clinical studies. Fourteen
single compounds were reported to have antidrug resistance activity for the first
time. In vitro, compounds were able to overcome drug resistance at nontoxic or
subtoxic concentrations, in a dose-dependent manner, by inhibiting drug
transporters, cell detoxification capacity, or cell apoptosis sensitivity.
Studies in vivo showed that single compounds, herbal extract, and formulas had
potent antidrug resistance activities. Importantly, many single compounds, herbal
extracts, and formulas have been used clinically to treat various diseases
including cancer. The review provides comprehensive data on use of natural
compounds to overcome cancer cell drug resistance in China, which may facilitate
the therapeutic development of natural products for clinical management of cancer
drug resistance.
PMID- 26421053
TI - Validation of a RP-HPLC-DAD Method for Chamomile (Matricaria recutita)
Preparations and Assessment of the Marker, Apigenin-7-glucoside, Safety and Anti
Inflammatory Effect.
AB - Chamomile is a medicinal plant, which presents several biological effects,
especially the anti-inflammatory effect. One of the compounds related to this
effect is apigenin, a flavonoid that is mostly found in its glycosylated form,
apigenin-7-glucoside (APG), in natural sources. However, the affectivity and
safety of this glycoside have not been well explored for topical application. In
this context, the aim of this work was to develop and validate a reversed-phase
high-performance liquid chromatography (RP-HPLC-DAD) method to quantify APG in
chamomile preparations. Additionally, the safety and the anti-inflammatory
potential of this flavonoid were verified. The RP-HPLC-DAD method was developed
and validated with linearity at 24.0-36.0 MUg/mL range (r = 0.9994). Intra- and
interday precision (RSD) were 0.27-2.66% and accuracy was 98.27-101.21%. The
validated method was applied in the analysis of chamomile flower heads, glycolic
extract, and Kamillen cream, supporting the method application in the quality
control of chamomile preparations. Furthermore, the APG safety was assessed by
MTT cytotoxicity assay and mutagenic protocols and the anti-inflammatory activity
was confirmed by a diminished TNF-alpha production showed by mice macrophages
treated with APG following LPS treatment.
PMID- 26421054
TI - A sustained high fat diet for two years decreases IgM and IL-1 beta in ageing
Wistar rats.
AB - BACKGROUND: The immune system undergoes several alterations of innate and
adaptive immunity during ageing. The main features of the aged immune system are
a reduced diversity of T cell receptors and a reduced activity of innate immune
cells with subsequent changes in adaptive immunity resulting in a less effective,
less specific, and dys-regulated immune response and in an increased
susceptibility towards infection, malignancy, and autoimmunity. The process is
referred to as immunosenescence and is also modulated by environmental modifiers,
such as dietary factors. High fat diet (HFD), via direct modulation of immune
cell function by fatty acids and/or increased body fat mass, influences immune
function. However, it is not clear whether HFD is beneficial or detrimental for
the functioning of the ageing immune system. METHODS: Male Wistar rats fed with
either a high fat diet (HFD 43 en% of fat) or control diet (SD, 25 en% of fat)
over up to 24 month and were analyzed for plasma IL-1beta, IL-6, TNF, IgM, IgG1,
IgA, IgG2a, IgG2b, IgG2c, light chains lambda and kappa, testosterone, prolactin
and percentage of splenic B cells and apoptosis rate, respectively. RESULTS: In
general, all analyzed immunoglobuline isotypes increased with age, except for
IgA. This increase was attenuated by HFD. In HFD and SD rats the percentage of B
cells in the spleen and also their apoptotic rate was lower in aged as compared
to young animals with no additional diet-induced effect. Testosterone and
prolactin levels were lower in old animals, as expected. There was a statistical
trend towards an increased prolactin/testosterone ratio in middle aged (6-12
monthsnth) HFD rats as compared to SD. IL-6 was neither affected by HFD nor age.
On the other hand, HFD rats showed a decrease in IL-1beta as compared to SD,
which correlated with the above-mentioned suppressive effect on immunoglobulin
isotypes, especially IgM. CONCLUSION: In Wistar rats, HFD reveals an
immunosuppressive effect in ageing animals by decreasing immunoglobulins,
especially IgM, and IL-1beta when compared to SD.
PMID- 26421055
TI - Reconstruction Method for Optical Tomography Based on the Linearized Bregman
Iteration with Sparse Regularization.
AB - Optical molecular imaging is a promising technique and has been widely used in
physiology, and pathology at cellular and molecular levels, which includes
different modalities such as bioluminescence tomography, fluorescence molecular
tomography and Cerenkov luminescence tomography. The inverse problem is ill-posed
for the above modalities, which cause a nonunique solution. In this paper, we
propose an effective reconstruction method based on the linearized Bregman
iterative algorithm with sparse regularization (LBSR) for reconstruction.
Considering the sparsity characteristics of the reconstructed sources, the
sparsity can be regarded as a kind of a priori information and sparse
regularization is incorporated, which can accurately locate the position of the
source. The linearized Bregman iteration method is exploited to minimize the
sparse regularization problem so as to further achieve fast and accurate
reconstruction results. Experimental results in a numerical simulation and in
vivo mouse demonstrate the effectiveness and potential of the proposed method.
PMID- 26421056
TI - Numerical Methods and Applications in Biomechanical Modeling 2014.
PMID- 26421057
TI - Suicidality among adolescents engaging in nonsuicidal self-injury (NSSI) and
firesetting: the role of psychosocial characteristics and reasons for living.
AB - BACKGROUND: Co-occurrence of problem behaviors, particularly across internalizing
and externalizing spectra, increases the risk of suicidality (i.e., suicidal
ideation and attempt) among youth. METHODS: We examined differences in
psychosocial risk factors across levels of suicidality in a sample of 77 school
based adolescents engaging in both nonsuicidal self-injury (NSSI) and repeated
firesetting. Participants completed questionnaires assessing engagement in
problem behaviors, mental health difficulties, negative life events, poor coping,
impulsivity, and suicidality. RESULTS: Adolescents endorsing suicidal ideation
reported greater psychological distress, physical and sexual abuse, and less
problem solving/goal pursuit than those with no history of suicidality;
adolescents who had attempted suicide reported more severe NSSI, higher rates of
victimization and exposure to suicide, relative to those with suicidal ideation
but no history of attempt. Additional analyses suggested the importance of coping
beliefs in protecting against suicidality. CONCLUSIONS: Clinical implications and
suggestions for future research relating to suicide prevention are discussed.
PMID- 26421059
TI - The functions of nonsuicidal self-injury: converging evidence for a two-factor
structure.
AB - Research has identified more than a dozen functions of non-suicidal self-injury
(NSI), but the conceptual and empirical overlap among these functions remains
unclear. The present study examined the structure of NSI functions in two large
samples of patients receiving acute-care treatment for NSI. Two different
measures of NSI functions were utilized to maximize generalizability of findings:
one sample (n = 946) was administered the Inventory of Statements About Self
injury (ISAS; Klonsky and Glenn in J Psychopathol Behav Assess 31:215-219, 2009),
and a second sample (n = 211) was administered the Functional Assessment of Self
Mutilation (FASM; Lloyd et al. in Self-mutilation in a community sample of
adolescents: descriptive characteristics and provisional prevalence rates. Poster
session at the annual meeting of the Society for Behavioral Medicine, New
Orleans, LA, 1997). Exploratory factor analyses revealed that both measures
exhibited a robust two-factor structure: one factor represented Intrapersonal
functions, such as affect regulation and anti-dissociation, and a second factor
represented Social functions, such as interpersonal influence and peer bonding.
In support of the two-factor structure's construct validity, the factors
exhibited a pattern of correlations with indicators of NSI severity that was
consistent with past research and theory. Findings have important implications
for theory, research, and treatment. In particular, the two-factor framework
should guide clinical assessment, as well as future research on the implications
of NSI functions for course, prognosis, treatment, and suicide risk.
PMID- 26421058
TI - Parents of youth who self-injure: a review of the literature and implications for
mental health professionals.
AB - Non-suicidal self-injury (NSSI) is a common mental health concern among youth,
and parents can be valuable supports for these youth. However, youth NSSI can
have a significant impact on parents' wellbeing, which may in turn alter parents'
ability to support the youth. To date, no single article has consolidated the
research on parents of youth who self-injure. This review synthesizes the
literature on parent factors implicated in youth NSSI risk, the role of parents
in help-seeking and intervention for youth NSSI, and the impact of youth NSSI on
parent wellbeing and parenting. Clinical implications for supporting parents as
they support the youth are also discussed, and recommendations for future
research are outlined.
PMID- 26421060
TI - Microdeletions in 9q33.3-q34.11 in five patients with intellectual disability,
microcephaly, and seizures of incomplete penetrance: is STXBP1 not the only
causative gene?
AB - BACKGROUND: Most microdeletions involving chromosome sub-bands 9q33.3-9q34.11 to
this point have been detected by analyses focused on STXBP1, a gene known to
cause early infantile epileptic encephalopathy 4 and other seizure phenotypes.
Loss-of-function mutations of STXBP1 have also been identified in some patients
with intellectual disability without epilepsy. Consequently, STXBP1 is widely
assumed to be the gene causing both seizures and intellectual disability in
patients with 9q33.3-q34.11 microdeletions. RESULTS: We report five patients with
overlapping microdeletions of chromosome 9q33.3-q34.11, four of them previously
unreported. Their common clinical features include intellectual disability,
psychomotor developmental delay with delayed or absent speech, muscular
hypotonia, and strabismus. Microcephaly and short stature are each present in
four of the patients. Two of the patients had seizures. De novo deletions range
from 1.23 to 4.13 Mb, whereas the smallest deletion of 432 kb in patient 3 was
inherited from her mother who is reported to have mild intellectual disability.
The smallest region of overlap (SRO) of these deletions in 9q33.3 does not
encompass STXBP1, but includes two genes that have not been previously associated
with disease, RALGPS1 and GARNL3. Sequencing of the two SRO genes RALGPS1 and
GARNL3 in at least 156 unrelated patients with mild to severe idiopathic
intellectual disability detected no causative mutations. Gene expression analyses
in our patients demonstrated significantly reduced expression levels of GARNL3,
RALGPS1 and STXBP1 only in patients with deletions of the corresponding genes.
Thus, reduced expression of STXBP1 was ruled out as a cause for seizures in our
patient whose deletion did not encompass STXBP1. CONCLUSIONS: We suggest that
microdeletions of this region on chromosome 9q cause a clinical spectrum
including intellectual disability, developmental delay especially concerning
speech, microcephaly, short stature, mild dysmorphisms, strabismus, and seizures
of incomplete penetrance, and may constitute a new contiguous gene deletion
syndrome which cannot completely be explained by deletion of STXBP1.
PMID- 26421061
TI - Dose-dependent alcohol-induced alterations in chromatin structure persist beyond
the window of exposure and correlate with fetal alcohol syndrome birth defects.
AB - BACKGROUND: In recent years, we have come to recognize that a multitude of in
utero exposures have the capacity to induce the development of congenital and
metabolic defects. As most of these encounters manifest their effects beyond the
window of exposure, deciphering the mechanisms of teratogenesis is incredibly
difficult. For many agents, altered epigenetic programming has become suspect in
transmitting the lasting signature of exposure leading to dysgenesis. However,
while several chemicals can perturb chromatin structure acutely, for many agents
(particularly alcohol) it remains unclear if these modifications represent
transient responses to exposure or heritable lesions leading to pathology.
RESULTS: Here, we report that mice encountering an acute exposure to alcohol on
gestational Day-7 exhibit significant alterations in chromatin structure (histone
3 lysine 9 dimethylation, lysine 9 acetylation, and lysine 27 trimethylation) at
Day-17, and that these changes strongly correlate with the development of
craniofacial and central nervous system defects. Using a neural cortical stem
cell model, we find that the epigenetic changes arising as a consequence of
alcohol exposure are heavily dependent on the gene under investigation, the dose
of alcohol encountered, and that the signatures arising acutely differ
significantly from those observed after a 4-day recovery period. Importantly, the
changes observed post-recovery are consistent with those modeled in vivo, and
associate with alterations in transcripts encoding multiple homeobox genes
directing neurogenesis. Unexpectedly, we do not observe a correlation between
alcohol-induced changes in chromatin structure and alterations in transcription.
Interestingly, the majority of epigenetic changes observed occur in marks
associated with repressive chromatin structure, and we identify correlative
disruptions in transcripts encoding Dnmt1, Eed, Ehmt2 (G9a), EzH2, Kdm1a, Kdm4c,
Setdb1, Sod3, Tet1 and Uhrf1. CONCLUSIONS: These observations suggest that the
immediate and long-term impacts of alcohol exposure on chromatin structure are
distinct, and hint at the existence of a possible coordinated epigenetic response
to ethanol during development. Collectively, our results indicate that alcohol
induced modifications to chromatin structure persist beyond the window of
exposure, and likely contribute to the development of fetal alcohol syndrome
associated congenital abnormalities.
PMID- 26421062
TI - Prenatal ethanol exposure alters adult hippocampal VGLUT2 expression with
concomitant changes in promoter DNA methylation, H3K4 trimethylation and miR-467b
5p levels.
AB - BACKGROUND: Maternal consumption of alcohol during pregnancy is associated with a
range of physical, cognitive and behavioural outcomes in the offspring which are
collectively called foetal alcohol spectrum disorders. We and others have
proposed that epigenetic modifications, such as DNA methylation and post
translational histone modifications, mediate the effects of prenatal alcohol
exposure on gene expression and, ultimately, phenotype. Here we use an inbred
C57BL/6J mouse model of early gestational ethanol exposure equivalent,
developmentally, to the first 3-4 weeks of pregnancy in humans to examine the
long-term effects on gene expression and epigenetic state in the hippocampus.
RESULTS: Gene expression analysis in the hippocampus revealed sex- and age
specific up-regulation of solute carrier family 17 member 6 (Slc17a6), which
encodes vesicular glutamate transporter 2 (VGLUT2). Transcriptional up-regulation
correlated with decreased DNA methylation and enrichment of histone H3 lysine 4
trimethylation, an active chromatin mark, at the Slc17a6 promoter. In contrast to
Slc17a6 mRNA levels, hippocampal VGLUT2 protein levels were significantly
decreased in adult ethanol-exposed offspring, suggesting an additional level of
post-transcriptional control. MicroRNA expression profiling in the hippocampus
identified four ethanol-sensitive microRNAs, of which miR-467b-5p was predicted
to target Slc17a6. In vitro reporter assays showed that miR-467b-5p specifically
interacted with the 3'UTR of Slc17a6, suggesting that it contributes to the
reduction of hippocampal VGLUT2 in vivo. A significant correlation between
microRNA expression in the hippocampus and serum of ethanol-exposed offspring was
also observed. CONCLUSIONS: Prenatal ethanol exposure has complex transcriptional
and post-transcriptional effects on Slc17a6 (VGLUT2) expression in the mouse
hippocampus. These effects are observed following a relatively moderate exposure
that is restricted to early pregnancy, modelling human consumption of alcohol
before pregnancy is confirmed, and are only apparent in male offspring in
adulthood. Our findings are consistent with the idea that altered epigenetic
and/or microRNA-mediated regulation of glutamate neurotransmission in the
hippocampus contributes to the cognitive and behavioural phenotypes observed in
foetal alcohol spectrum disorders. Although further work is needed in both mice
and humans, the results also suggest that circulating microRNAs could be used as
biomarkers of early gestational ethanol exposure and hippocampal dysfunction.
PMID- 26421063
TI - Transgelin gene is frequently downregulated by promoter DNA hypermethylation in
breast cancer.
AB - BACKGROUND: CpG hypermethylation in gene promoters is a frequent mechanism of
tumor suppressor gene silencing in various types of cancers. It usually occurs at
early steps of cancer progression and can be detected easily, giving rise to
development of promising biomarkers for both detection and progression of cancer,
including breast cancer. 5-aza-2'-deoxycytidine (AZA) is a DNA demethylating and
anti-cancer agent resulting in induction of genes suppressed via DNA
hypermethylation. RESULTS: Using microarray expression profiling of AZA- or DMSO
treated breast cancer and non-tumorigenic breast (NTB) cells, we identified for
the first time TAGLN gene as a target of DNA hypermethylation in breast cancer.
TAGLN expression was significantly and frequently downregulated via promoter DNA
hypermethylation in breast cancer cells compared to NTB cells, and also in 13/21
(61.9 %) of breast tumors compared to matched normal tissues. Analyses of public
microarray methylation data showed that TAGLN was also hypermethylated in 63.02 %
of tumors compared to normal tissues; relapse-free survival of patients was worse
with higher TAGLN methylation; and methylation levels could discriminate between
tumors and healthy tissues with 83.14 % sensitivity and 100 % specificity.
Additionally, qRT-PCR and immunohistochemistry experiments showed that TAGLN
expression was significantly downregulated in two more independent sets of breast
tumors compared to normal tissues and was lower in tumors with poor prognosis.
Colony formation was increased in TAGLN silenced NTB cells, while decreased in
overexpressing BC cells. CONCLUSIONS: TAGLN gene is frequently downregulated by
DNA hypermethylation, and TAGLN promoter methylation profiles could serve as a
future diagnostic biomarker, with possible clinical impact regarding the
prognosis in breast cancer.
PMID- 26421064
TI - Analysis of DNA methylation landscape reveals the roles of DNA methylation in the
regulation of drug metabolizing enzymes.
AB - BACKGROUND: Drug metabolizing enzymes (DMEs) exhibit dramatic inter- and intra
individual variability in expression and activity. However, the mechanisms
determining this variability have not been fully elucidated. The aim of this
study was to evaluate the biological significance of DNA methylation in the
regulation of DME genes by genome-wide integrative analysis. RESULTS: DNA
methylation and mRNA expression profiles of human tissues and hepatoma cells were
examined by microarrays. The data were combined with GEO datasets of liver
tissues, and integrative analysis was performed on selected DME genes. Detailed
DNA methylation statuses at individual CpG sites were evaluated by DNA
methylation mapping. From analysis of 20 liver tissues, highly variable DNA
methylation was observed in 37 DME genes, 7 of which showed significant inverse
correlations between DNA methylation and mRNA expression. In hepatoma cells,
treatment with a demethylating agent resulted in upregulation of 5 DME genes,
which could be explained by DNA methylation status. Interestingly, some DMEs were
suggested to act as tumor-suppressor or housekeeper based on their unique DNA
methylation features. Moreover, tissue-specific and age-dependent expression of
UDP-glucuronosyltransferase 1A splicing variants was associated with DNA
methylation status of individual first exons. CONCLUSIONS: Some DME genes were
regulated by DNA methylation, potentially resulting in inter- and intra
individual differences in drug metabolism. Analysis of DNA methylation landscape
facilitated elucidation of the role of DNA methylation in the regulation of DME
genes, such as mediator of inter-individual variability, guide for correct
alternative splicing, and potential tumor-suppressor or housekeeper.
PMID- 26421065
TI - Is Endovascular Aneurysm Repair a Relative Contraindication for Patients with
Preoperative Renal Dysfunction?
AB - Whether endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA)
is a relative contraindication in patients with preoperative renal dysfunction
(Pre-RD), remains controversial because the contrast medium may induce
nephrotoxicity. In this study 1658 patients were treated at ten Japanese medical
centers between January 2005 and March 2011 (Open surgery (OS) vs. EVAR: n = 1270
vs. n = 388). They were retrospectively analyzed. Multiple logistic regression
analysis (MLRA) with pre- and intra-operative variables was applied to all
patients. The endpoints induced onset of new dialysis and postoperative renal
dysfunction (Post-RD), were defined as a 50% decrease or more from the
preoperative estimated glomerular filtration rate (eGFR) level. RESULTS: Early
mortality, Post-RD, incidence of new dialysis in all patients were 1.6% (OS: EVAR
= 1.9%:0.8%), 6% (OS: EVAR = 8%:2.3%) and 1.4% (OS: EVAR = 1.5%:1.0%)
respectively. MLRA identified operation time, clamp of renal artery as risk
factors for Post-RD, and operation time and Pre-eGFR level as risk factors for
new dialysis. CONCLUSION: Although Post-RD was more frequently observed in the OS
group, MLRA showed that the choice of OS or EVAR was not a risk factor for Post
RD and new dialysis. It was strongly suggested that using contrast medium during
EVAR is not a contraindication to AAA repair in patients with Pre-RD. (This
article is a translation of J Jpn Coll Angiol 2014; 54: 13-18.).
PMID- 26421066
TI - Long-Term Results of Treatment for Critical Limb Ischemia.
AB - From 2001 to 2012, arterial reconstruction was performed in 306 out of 497 limbs
(62%) with critical limb ischemia. The reasons for non-vascularization include
high operative risk (36%), extended necrosis or infection (20%), and technical
issues (15%). Cumulative patency and limb salvage in collagen disease were
significantly worse compared to arteriosclerosis obliterans. Cumulative limb
salvage, amputation free survival (AFS), and major adverse limb event and
perioperative death (MALE + POD) in patients with end-stage renal disease (ESRD)
were significantly worse compared to patients without ESRD, but not significant
with regards to graft patency. Our finding suggests that aggressive arterial
reconstruction provides satisfactory long-term results in critical limb ischemia
so long as case selection for revascularization is properly made. (This article
is a translation of J Jpn Coll Angiol 2014; 54: 5-11.).
PMID- 26421067
TI - Efficacy of Ultrasonography at the Ankle Level for Estimation of Pedal
Microcirculation.
AB - Chronic wounds due to diabetes mellitus (DM) and/or peripheral arterial disease
(PAD) often occur in the pedal region peripheral to the ankle. To predict wound
healing potential of limb ulcers, skin perfusion pressure (SPP) and
transcutaneous oxygen tension (TcPO2) have recently become popular as the
parameters that reflect skin microcirculation. On the other hand, ultrasonography
for the macrocirculatory vessels has already prevailed widely as the standard
vascular investigation. The skin microcirculation peripheral to the ankle
probably depends on the macrocirculatory blood flow at the ankle level. Thus,
this study aims to estimate whether the blood flow of the anterior tibial artery
(ATA) and the posterior tibial artery, at the ankle level, reflect the values of
SPP and TcPO2 on the foot. The protocol enrolled 88 patients (122 limbs) with
foot ulcers due to DM and/or PAD. The statistical analysis revealed that the sum
of blood flow of the ATA and the PTA (posterior tibial artery), at the ankle
level, significantly correlated with SPP on the foot. The findings support the
availability of conventional ultrasonographic investigation to estimate
microcirculation of the foot crucial for wound healing. (This article is a
translation of J Jpn Coll Angiol 2014; 54: 45-50.).
PMID- 26421068
TI - Occurrence of Deep Vein Thrombosis among Hospitalized Non-Surgical Japanese
Patients.
AB - OBJECTIVE: To estimate the frequency of deep vein thrombosis (DVT) among non
surgical inpatients, and to evaluate the D-dimer assay as a screening tool for
DVT. METHODS: Subjects were non-surgical inpatients aged 20 years or older who
had been bedridden for at least 24 hours and had moderate-to-high risk factors
for DVT. We assessed the presence of DVT by venous ultrasonography. Patients who
received a diagnosis of venous thromboembolism (VTE) before admission, who had
symptoms or findings of VTE at admission, or who had surgery or trauma within the
past 3 months before admission were excluded. RESULTS: DVT was confirmed in 96 of
525 patients (18.3%). In a logistic regression analysis, longer duration of
hospitalization, higher D-dimer value, and history of cancer surgery were
significantly associated with the occurrence of DVT. The D-dimer assay showed
high sensitivity (96.1%) and high negative predictive value (97.6%). CONCLUSION:
Non-surgical inpatients with a long-term hospitalization or history of cancer
surgery have a risk for DVT, and need to be considered for added DVT preventive
measures as recommended in the prevention guidelines. In addition, the D-dimer
assay is beneficial for the screening of DVT in medical practice.
PMID- 26421069
TI - Open Surgical Repair Can Be One Option for the Treatment of Persistent Type II
Endoleak after EVAR.
AB - PURPOSES: Endovascular abdominal aortic aneurysm repair (EVAR) is an increasingly
used method of repairing abdominal aortic aneurysm (AAA). However, the treatment
of persistent type II endoleak is still a controversial issue. Five cases are
reported here in which we performed open surgical repair of growing aneurysm due
to persistent type II endoleak. METHOD: Totally 128 EVAR cases were
retrospectively reviewed, which were operated in our hospital from April 2008 to
October 2013. These cases were followed by periodical contrast-enhanced computed
tomography (CT) after EVAR. When persistent type II endoleak caused aneurysm sac
growth, we performed surgical repair method for the first line treatment. In the
operation, we incised the aneurysm sac by abdominal small median incision
approach and sutured lumber arteries from inside of aneurysm sac and tied
inferior mesenteric artery (IMA) in addition to aneurysmorrhaphy. Contrast
enhanced CT scanning was performed in a week after open repair for the
confirmation of complete treatment. RESULTS: Five of 128 cases (3.9%) were needed
to be surgically repaired because of aneurysm sac growth (>5 mm), including two
ruptured AAA cases. All patients recovered uneventfully. Contrast-enhanced CT
scanning performed a week after these operations showed no endoleak and intact
stent grafts and reduction of the aneurysm size. CONCLUSION: We believe open
surgical repair method of persistent type II endoleak with aneurysm expansion is
secure method, and can be one of the preferable options for this life threatening
complication after EVAR.
PMID- 26421070
TI - Pre- and Intraoperative Predictors of Delirium after Open Abdominal Aortic
Aneurysm Repair.
AB - OBJECTIVES: We reviewed our series of patients who underwent open abdominal
aortic aneurysm (AAA) repair and constructed a prediction model for postoperative
delirium. METHODS: 397 patients who underwent open AAA repair at our institution
between April 2005 and June 2013 were retrospectively reviewed. Postoperative
delirium was diagnosed from the patients' medical records according to the
Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV)
criteria. Mental alterations resulting from postoperative cerebrovascular events
or preexisting mental disorders were excluded. Parameters with significant
differences on univariate analysis were subjected to a logistic regression
analysis. RESULTS: There were 46 patients (11.5%) diagnosed with postoperative
delirium. The following parameters were significant in the univariate analysis:
age, history of stroke, hyperlipidemia, forced expiratory volume in 1 s (FEV1),
percent vital capacity (%VC), and blood urea nitrogen (BUN) level. A logistic
regression analysis revealed that an age >=70 years (odds ratio [95% confidence
interval], 3.342 [1.437-7.774]), blood loss >=1517 mL (2.707 [1.359-5.391]), and
the absence of hyperlipidemia (2.154 [1.060-4.374]) were significant risk
factors. CONCLUSIONS: Older patients with substantial intraoperative blood loss
require highly vigilant postoperative care. Further studies are necessary to
elucidate the relationship between cholesterol and delirium.
PMID- 26421071
TI - Popliteal Retrograde Approach is Effective and Safe for Superficial Femoral
Artery Chronic Total Occlusion.
AB - OBJECTIVE: Endovascular treatment (EVT) using a popliteal approach is effective
for superficial femoral artery (SFA) chronic total occlusion (CTO); however, its
effectiveness, safety, and consequent complications are unclear. MATERIALS AND
METHODS: We studied 324 consecutive EVTs (in 187 patients) performed at three
centers between April 2008 and March 2013, and selected all EVTs that included
SFA CTO regions. A total of 91 EVTs (in 65 patients) were included and divided
into two groups; "with popliteal approach" (WPA) and "without popliteal approach"
(WOPA). RESULTS: Despite higher rates of hypertension (WPA, 88.9% vs. WOPA,
69.1%; p = 0.04) and CTO length >200 mm (55.6% vs. 28.3%, respectively; p <0.01),
the primary success rate was better in the WPA group (97.2% vs. 78.2%,
respectively; p <0.01); however, both total complication rate and major
complication rate were not significantly different. We compared popliteal
puncture using a sheath and using a microcatheter alone. There were no
significant differences between sheath and microcatheter use in terms of primary
success rates (95.5% vs. 100%, respectively; p = 0.61) and puncture site
complications (22.7% vs. 14.2%, respectively; p = 0.53). CONCLUSION: A popliteal
approach improved the primary success rate of EVT for SFA CTO.
PMID- 26421072
TI - Ankle-Brachial Index, Toe-Brachial Index, and Pulse Volume Recording in Healthy
Young Adults.
AB - OBJECTIVE: To clarify the characteristics of ankle-brachial index (ABI), toe
brachial index (TBI), and pulse volume recording (PVR) of the ankle with brachial
ankle pulse wave velocity (baPWV) in healthy young adults. MATERIAL AND METHODS:
We analyzed ABI, TBI, baPWV, and PVR in the ankle of healthy adults aged 20 to 25
years (median, 20 years) using an automatic oscillometric device between 2002 and
2013. The ABI, baPWV, and PVR in 1282 legs of 641 subjects (301 men and 340
women) and the TBI in 474 toes of 237 subjects (117 men and 120 women) were
evaluated. RESULTS: The measured values showed no bilateral differences. ABI and
baPWV were higher in men than in women, but TBI was similar in both sexes. ABI
<1.0 was observed in 18.1% of the legs in men and in 25.6% in women. TBI <0.7 was
observed in 16.2% of the toes in men and 19.1% in women. For ankle PVR, the %
mean arterial pressure was higher in women than in men. The upstroke time was
<180 ms in most subjects. CONCLUSIONS: For young people, ABI <1.0 or TBI <0.7 may
not always indicate vascular abnormalities. When evaluating circulatory indexes,
age and sex should be considered.
PMID- 26421073
TI - Accuracy of Venous Filling Index on Standing (VFIst) and Pure Regurgitation Index
(PRI), a Novel Index Obtained by Air Plethysmography, for Detecting Venous
Reflux.
AB - OBJECTIVE: To evaluate the accuracy of venous filling index on standing (VFIst)
and a new index named pure regurgitation index (PRI), obtained by air
plethysmography, for detecting venous reflux. MATERIALS AND METHODS: One hundred
and sixty-one healthy subjects (161 limbs) and 180 varicose vein patients (180
limbs) were investigated. All subjects underwent duplex ultrasonography for
verifying venous reflux and air plethysmography to obtain hemodynamic parameters
such as VFIst, VFI in the supine position (VFIsu), and the maximum arterial
inflow rate. To evaluate the accuracy of VFIst and PRI (= (VFIst - VFIsu)/body
mass index), receiver operating characteristics curves were created. RESULTS: The
optimal cut-off value, sensitivity, specificity, and area under the curve,
obtained from analyzing the receiver operating characteristics curves, of VFIst
vs. PRI were 2.058 mL/s vs. 0.059 mL . m(2)/s . kg, 93.3% vs. 90.3%, 88.8% vs.
91.3%, and 0.954 vs. 0.964, respectively. CONCLUSIONS: This study indicates that
while both VFIst and PRI are highly accurate indicators of venous reflux, PRI,
which is not affected by the arterial inflow rate and body mass index, is
slightly superior to VFIst, especially in subjects with greater body mass index.
PMID- 26421074
TI - Operative Management of Hilar Renal Artery Aneurysm in a Pregnant Patient.
AB - Complications of renal artery aneurysms (RAAs) can be life threatening and
include the spontaneous rupture which may lead to severe retroperitoneal
hemorrhage, loss of the kidney, or death. As the incidence and diagnosis of RAAs
is expected to rise, it is becoming increasingly important to enhance our
awareness and knowledge of this rare clinical entity. Here, we present the case
of a hilar right RAA and the surgical approach for primary repair during the
postpartum period. Additionally, we discuss current pathophysiologic mechanisms,
associated symptoms as well as current treatment modalities for RAAs.
PMID- 26421075
TI - Extra-Anatomic Bypass Operation for an Infected Aortic Arch Aneurysm with Broad
Mediastinal Abscess: A Case Report.
AB - We encountered an informative case of infected aortic arch aneurysm. The proximal
descending aorta, left common carotid artery, and left subclavian artery were
severely involved in an abscess; thus, typical in situ reconstruction of the arch
was considered impossible. Therefore, to secure more distal branches appropriate
for anastomosis, a modified extra-anatomic arch repair was performed through
additional incisions. The patient developed renal and respiratory failure and
died of septicemia five and a half months after the operation. However,
postoperative computed tomograms demonstrated that the abscess had disappeared.
PMID- 26421076
TI - Effectiveness of the Use of Near-Infrared Spectroscopy to Treat Acute Type A
Aortic Dissection Complicated with Limb Ischemia: Report of a Case.
AB - We report an effectiveness of the use of near-infrared spectroscopy to evaluate
the limb perfusion, which helps to continuously measure the tissue oxygen index
of bilateral legs in treating acute type A aortic dissection complicated with
limb ischemia. A 62-year-old man underwent total arch replacement for acute type
A aortic dissection with limb ischemia. Intraoperative retrograde true lumen
perfusion via bilateral femoral arteries during cardiopulmonary bypass improved
ischemic condition of bilateral legs before the resection of primary intimal
tear, and the use of near-infrared spectroscopy made it possible to assess
additional revascularizations to the lower limbs were required or not.
PMID- 26421077
TI - Repair of Acute Type B Aortic Dissection Complicated by Aortic Rupture with
Debranching Thoracic Endovascular Aortic Repair and Left Subclavian Artery
Occlusion Using Amplatzer Vascular Plug II.
AB - An 88-year-old man with severe chest pain and syncope was admitted to our
hospital. Contrast-enhanced computed tomography (CT) revealed acute type B aortic
dissection with rupture. Considering age and operative risk, we performed
emergency thoracic aortic endovascular repair with two-debranching of the left
common carotid and left subclavian arteries. To prevent type II endoleak, we used
Amplatzer Vascular Plug (AVP) II for left subclavian artery embolization.
Postoperative contrast-enhanced CT showed no type II endoleak and rupture site
exclusion. As postoperative persistent blood flow to the primary entry or rupture
site causes re-rupture, AVP II was crucial in preventing type II endoleak.
PMID- 26421078
TI - Delayed Intestinal Ischemia after Surgery for Type A Acute Aortic Dissection.
AB - We report a rare case of delayed intestinal ischemia after total arch replacement
for type A acute aortic dissection. At the onset of acute aortic dissection,
computed tomography (CT) angiography revealed celiac trunk occlusion and
progressive dissection into the superior mesenteric artery without stenosis.
However, following total arch replacement, visceral malperfusion was not detected
by exploratory laparotomy. On postoperative day 12, the patient developed
paralytic ileus without an elevated lactate level. CT angiography revealed new
superior mesenteric artery stenosis by a thrombosed false lumen with persistent
celiac trunk occlusion. Endovascular treatment including stent implantation
resolved intestinal ischemia.
PMID- 26421079
TI - Open Surgical Bypass for Superficial Femoral Artery Occlusion Caused by Blunt
Trauma.
AB - Blunt vascular trauma of the lower extremities brings about a high amputation
rate, because other organ injuries disturb revascularization. We experienced a
case of a superficial femoral artery occlusion caused by blunt trauma. The
patient also had a femoral bone fracture and a large skin defect with deep
muscular injuries of the thigh. We performed a femoropopliteal (FP) bypass using
a saphenous vein which was routed through the contaminated wound. Postoperative
vacuum-assisted closure therapy was used to prevent graft infection. Surgical
bypasses using saphenous veins are approved treatments for arterial occlusions
from blunt trauma if the grafts go through contaminated wounds.
PMID- 26421080
TI - Unusual Cases of Hypothenar Hammer Syndrome.
AB - OBJECTIVE: Hypothenar hammer syndrome (HHS) is a rare occupational disease. The
risk group of HHS is patient whose dominate hand used as a hammer. Our study
report unusually cases in Chiang Mai University Hospital. RESULT: 19 year-old
basketball player had right ulnar artery aneurysm for two months. After
operation, his symptom was relieved and returned to play basketball again. 65
year-old housekeeper had non-dominated hand ulnar artery aneurysm for two years.
After operation she still had hand claudication due to poor run-off vessel.
CONCLUSION: HHS is previously state in risk group. But from our report there was
a risk in different occupation.
PMID- 26421081
TI - Open Surgery for Giant Bilateral Internal Iliac Artery Aneurysms with Compression
of Neighboring Abdominal Structures: A Case Report.
AB - We describe a patient with successfully treated giant bilateral internal iliac
artery aneurysms that were associated with acute renal failure secondary to
bilateral hydronephrosis, lumbosacral plexopathy, and ileus. After hemodialysis
for 1 month, the patient underwent graft replacement of the abdominal aorta and
iliac arteries, including complete obliteration of the internal iliac artery
branches, reconstruction of the inferior mesenteric artery, and ureterolysis.
Weaning from hemodialysis was achieved and postoperative renal function improved.
Although the patient had serious preoperative co-morbidities, emergency
traditional open surgery should be the gold standard for securely releasing
compression of the neighboring organs instead of endovascular treatment.
PMID- 26421082
TI - Early Stent Graft Perforation after Endovascular Repair for Pseudoaneurysm That
Was Associated with Clavicle Nonunion.
AB - We report the case of a 62-year-old man who experienced a left axillary artery
pseudoaneurysm that was secondary to nonunion of a 30-year-old left midshaft
clavicle fracture. He initially underwent endovascular repair using a self
expanding nitinol stent graft, which was perforated at postoperative day 5.
Therefore, we performed open repair with concomitant clavicle resection, and no
complications were observed during an approximately 6-year follow-up. We
recommend performing clavicle resection with vascular repair to prevent
recurrence in similar cases.
PMID- 26421083
TI - Surgical Treatment of a Giant Right Hepatic Artery Aneurysm with an Aberrant Left
Hepatic Artery: Report of a Case.
AB - Hepatic artery aneurysms are rare. We describe a case of a successful surgical
treatment of a giant hepatic aneurysm without revascularization. A 63-year-old
female was admitted to our department complaining of abdominal pain. Computed
tomography showed a thrombosed hepatic artery aneurysm measuring 5.5 cm in
diameter. A celiac angiography revealed an aberrant left hepatic artery and a
right hepatic aneurysm. Liver blood flow and the right hepatic aneurysm were
visualized via collateral pathway from the aberrant left hepatic artery. We
performed an aneurysmorrhaphy without revascularization. Postoperative course was
uneventful and the patient is doing well 3 months after surgery.
PMID- 26421084
TI - Embodied Information in Cognitive Tasks: Haptic Weight Sensations Affect Task
Performance and Processing Style.
AB - Research in the field of embodied cognition showed that incidental weight
sensations influence peoples' judgments about a variety of issues and objects.
Most studies found that heaviness compared to lightness increases the perception
of importance, seriousness, and potency. In two experiments, we broadened this
scope by investigating the impact of weight sensations on cognitive performance.
In Experiment 1, we found that the performance in an anagram task was reduced
when participants held a heavy versus a light clipboard in their hands. Reduced
performance was accompanied by an increase in the perceived effort. In Experiment
2, a heavy clipboard elicited a specific response heuristic in a two-alternative
forced-choice task. Participants showed a significant right side bias when
holding a heavy clipboard in their hands. After the task, participants in the
heavy clipboard condition reported to be more frustrated than participants in the
light clipboard condition. In both experiments, we did not find evidence for
mediated effects that had been proposed by previous literature. Overall, the
results indicate that weight effects go beyond judgment formation and highlight
new avenues for future research.
PMID- 26421085
TI - The Influence of Motor Imagery on Postural Sway: Differential Effects of Type of
Body Movement and Person Perspective.
AB - The present study examined the differential effects of kinesthetic imagery (first
person perspective) and visual imagery (third person perspective) on postural
sway during quiet standing. Based on an embodied cognition perspective, the
authors predicted that kinesthetic imagery would lead to activations in movement
relevant motor systems to a greater degree than visual imagery. This prediction
was tested among 30 participants who imagined various motor activities from
different visual perspectives while standing on a strain gauge plate. The results
showed that kinesthetic imagery of lower body movements, but not of upper body
movements, had clear effects on postural parameters (sway path length and
frequency contents of sway). Visual imagery, in contrast, had no reliable effects
on postural activity. We also found that postural effects were not affected by
the vividness of imagery. The results suggest that during kinesthetic motor
imagery participants partially simulated (re-activated) the imagined movements,
leading to unintentional postural adjustments. These findings are consistent with
an embodied cognition perspective on motor imagery.
PMID- 26421086
TI - Preface to Special Topic: Microfluidics in Drug Delivery.
AB - In this special topic of Biomicrofluidics, the importance of microfluidics in the
field of drug delivery is highlighted. Different aspects from cell-drug carrier
interactions, delivery vehicle assembly to novel drug delivery devices are
considered. The contributing reviews and original articles illustrate the
synergistic outcomes between these two areas of research with the aim to have a
positive impact on biomedical applications.
PMID- 26421087
TI - An off-the-shelf integrated microfluidic device comprising self-assembled
monolayers for protein array experiments.
AB - Microfluidic-based protein arrays are promising tools for life sciences, with
increased sensitivity and specificity. One of the drawbacks of this technology is
the need to create fresh surface chemistry for protein immobilization at the
beginning of each experiment. In this work, we attempted to include the process
of surface functionalization as part of the fabrication of the device, which
would substitute the time consuming step of surface functionalization at the
beginning of each protein array experiment. To this end, we employed a novel
surface modification using self-assembled monolayers (SAMs) to immobilize
biomolecules within the channels of a polydimethylsiloxane (PDMS) integrated
microfluidic device. As a model, we present a general method for depositing
siloxane-anchored SAMs, with 1-undecyl-thioacetate-trichlorosilane (C11TA) on the
silica surfaces. The process involved developing PDMS-compatible conditions for
both SAM deposition and functional group activation. We successfully demonstrated
the ability to produce, within an integrated microfluidic channel, a C11TA
monolayer with a covalently conjugated antibody. The antibody could then bind its
antigen with a high signal to background ratio. We further demonstrated that the
antibody was still active after storage of the device for a week. Integration of
the surface chemistry into the device as part of its fabrication process has
potential to significantly simplify and shorten many experimental procedures
involving microfluidic-based protein arrays. In turn, this will allow for broader
dissemination of this important technology.
PMID- 26421088
TI - Microfluidic sampling system for tissue analytics.
AB - We have developed a microfluidics based sampling system for tissue analytics. The
proof-of-concept of the sampling system was demonstrated by extracting lipid
samples from tissue biopsies. The sample collection system consists of a
disposable silicon based multiport microneedle integrated with polymer
microfluidics. The polymethyl methacrylate polymer microfluidic chip has a 10 MUl
sample reservoir and actuation membranes for liquid pumping. A special automated
robotic system was developed to control the positioning of the needle and the
sampling procedure on preselected spots on the tissue. Real breast cancer tissue
samples were used to test the feasibility of the sampling system. We successfully
measured indicative cancer biomarkers from the tissue surface.
Phosphatidylcholine and phosphoethanolamine were extracted from the tissue
membrane with methyl tert-butyl ether solvent and detected by mass spectrometry.
In the future, this tool could be used in characterization of preoperative
biopsies and tumour tissues removed during surgery.
PMID- 26421089
TI - An On-Site Thermoelectric Cooling Device for Cryotherapy and Control of Skin
Blood Flow.
AB - Cryotherapy involves the surface application of low temperatures to enhance the
healing of soft tissue injuries. Typical devices embody a remote source of
chilled water that is pumped through a circulation bladder placed on the
treatment site. In contrast, the present device uses thermoelectric refrigeration
modules to bring the cooling source directly to the tissue to be treated, thereby
achieving significant improvements in control of therapeutic temperature while
having a reduced size and weight. A prototype system was applied to test an
oscillating cooling and heating protocol for efficacy in regulating skin blood
perfusion in the treatment area. Data on 12 human subjects indicate that
thermoelectric coolers (TECs) delivered significant and sustainable changes in
perfusion for both heating (increase by (+/-SE) 173.0 +/- 66.0%, P < 0.005) and
cooling (decrease by (+/-SE) 57.7 +/- 4.2%, P < 0.0005), thus supporting the
feasibility of a TEC-based device for cryotherapy with local temperature
regulation.
PMID- 26421090
TI - Design of Novel Mixer and Applicator for Two-Component Surgical Adhesives.
AB - Current mixer and applicator devices on the market are not able to properly and
efficiently mix two-component surgical adhesives in small volumes necessary to
achieve economic viability. Furthermore, in these devices a significant amount of
adhesive is wasted during the application process, as material within the dead
space of the mixing chamber must be discarded. We have designed and demonstrated
a new active mixer and applicator system capable of rapidly and efficiently
mixing two components of an adhesive and applying it to the surgical site.
Recently, Messersmith et al. have developed a tissue adhesive inspired by the
mussel byssus and have shown that it is effective as a surgical sealant, and is
especially suited for wet environments such as in fetal surgery. Like some other
tissue sealants, this one requires that two components of differing viscosities
be thoroughly mixed within a specified and short time period. Through a
combination of compression and shear testing, we demonstrated that our device
could effectively mix the adhesive developed by Messersmith et al. and improve
its shear strength to significantly higher values than what has been reported for
vortex mixing. Overall, our mixer and applicator system not only has potential
applications in mixing and applying various adhesives in multiple surgical fields
but also makes this particular adhesive viable for clinical use.
PMID- 26421091
TI - Atypical Spitz Nevi: A Case Report and Review of the Literature.
AB - A case of atypical ("pagetoid") compound Spitz nevus on the face of a 2-year-old
girl is reported with a review of the literature. The nevus was composed of broad
but laterally demarcated compound proliferation of enlarged fusiform and
epithelioid melanocytes, with florid pagetoid scatter above the junction.
Immunohistochemical analyses revealed the Ki-67 proliferation index to be
relatively low. Given the histomorphological overlap with melanoma, an array
based comparative genomic hybridization approach revealed a subthreshold gain in
chromosome 1q and gain in distal chromosome 17q, with no other associated
chromosomal gains or losses. These molecular aberrations suggested a partially
transformed tumor, without adequate evidence for a molecular diagnosis of
melanoma. Because of the diagnostic dilemma posed by these lesions, recent
research has focused on molecular alterations that may help differentiate Spitz
tumors from malignant melanomas.
PMID- 26421092
TI - Intraoperative Chemosis During Resection of Lower Eyelid Lesion.
PMID- 26421093
TI - Unilateral Swollen Hand: A Rare Case of Primary Lymphedema Tarda.
PMID- 26421094
TI - [Neurological complication in rheumatoid arthritis: tetraparesia by C1-C2
dislocation].
PMID- 26421095
TI - [Angiographic appearance of angioid streaks complicated by bilateral choroidal
neovascularization].
PMID- 26421096
TI - Designing text-messaging (SMS) in HIV programs: ethics-framed recommendations
from the field.
AB - Text messages (SMS) are being increasingly integrated into HIV programs across
Southern Africa to improve patient adherence, linkage to care and provide psycho
social support. Careful attention needs to be paid to the design of SMS-based
interventions for clients of HIV-care services to ensure that any potential harm,
such as unwanted disclosure of HIV status, is minimized. In this article we
propose a set of best practice recommendations to ensure that any SMS-based
intervention considers ethical principles to safeguard safety, autonomy and
confidentiality of its targeted HIV-positive beneficiaries. This analysis draws
from our operational experience in Southern Africa in the design and conduct of
mHealth interventions in the frame of HIV projects. The recommendations, framed
in the context of the Belmont Report's three ethical pillars, may contribute to
more safely operationalize any SMS service integrated into an HIV program if
adopted by mHealth planners and implementers. We encourage actors to report on
the ethical and methodological pathways followed when conducting SMS-based
innovations to improve the wellbeing and quality provision of HIV-care for their
targeted clients.
PMID- 26421097
TI - Pneumothorax complicating isolated clavicle fracture.
AB - Isolated clavicle fractures are among the commonest of traumatic fractures in the
emergency department. Complications of isolated clavicle fractures are rare.
Pneumothorax has been described as a complication of a fractured clavicle only
rarely in English literature. In all the reported cases, the pneumothorax was
treated by a thoracostomy and the clavicle fracture was treated conservatively.
In our case, the pneumothorax required a chest drain insertion and the clavicle
fracture was treated surgically with good result.
PMID- 26421098
TI - [Sickle cell disease and biliary lithiasis - about two observations in Lubumbashi
(DR Congo)].
PMID- 26421099
TI - [Secondary pathological fractures of benign tumors in children: about 20 cases].
PMID- 26421100
TI - The clinical pattern of renal diseases in the nephrology in-patient unit of the
Yaounde General Hospital in Cameroon: a five-year audit.
AB - INTRODUCTION: Kidney diseases are a growing worldwide problem and one of the
major public health threats. We analyzed the spectrum of kidney diseases seen
over a five-year period in the nephrology in-patient unit of the Yaounde general
hospital. METHODS: This was a retrospective analysis of 225 medical records of
patients admitted from January 2005 to December 2009 in the unit with a discharge
diagnosis of kidney and urinary tract diseases. The first hospitalization was
considered for patients admitted several times for the same disease. Socio
demographic and clinical patient data were recorded. RESULTS: The patients mean
age was 44.8+/-16 years with 135 (60%) males and 211 (93.8%) emergency
admissions. All 139 (61.8%) patients with chronic kidney disease (CKD) had
chronic renal failure. Acute kidney injury (AKI) (28%), nephrotic syndrome
(7.6%), renal colic (1.3%) and acute pyelonephritis (1.3%) were other patterns
observed. Chronic glomerulonephritis (25.9%), hypertension (22.3%) and diabetes
(20.1%) were the main etiological factors of CKD. All AKI patients were in stage
RIFLE-F. AKI was secondary to parenchymal (58.7%), functional (25.4%) and
obstructive (15.9%) etiologies. Black water fever (36.4%), sepsis (22.7%), drugs
(18.2%), eclampsia (13.6%) and herbal concoctions (9.1%) were the etiologies of
acute tubular necrosis while enterocolitis (56.2%), heart failure (31.3%) and
digestive hemorrhage (12.5%) were the etiologies of functional AKI. CONCLUSION:
The clinical pattern of renal diseases is dominated by advanced CKD and AKI
secondary to preventable causes. This study suggests a need for an array of
actions including sensitization, continuous medical education and strengthening
of the health system.
PMID- 26421101
TI - Acute carpal tunnel syndrome of the hand following a cat bite.
AB - Cat bites at the hand are common situation in emergency departments. Neglected or
poorly supported, these lesions sometimes lead to serious injuries that may
compromise the function of the hand. Pasteurellamultocida is the most offending
germ in these lesions, despite their sensitivity to antibiotics; it can sometimes
lead to deep infections involving the skin, bones and joints. Acute carpal tunnel
syndrome is exceptional after cat bite. We report a case of a 56 Year old female
presenting with an acute carpal tunnel syndrome associated with compartment
syndrome of the right hand 6 days after a cat bite of her right thumb. The
patient was treated by surgery to relieve the median nerve. Microbiology
identified PasteurellaMultocida.
PMID- 26421102
TI - Knee megaprosthesis: a salvage solution for severe open and complex distal
femoral fracture associated with an ipsilateral brachial plexus injury (a case
report with literature review).
AB - Complex distal femoral fractures in the young patient often occur as a result of
high velocity trauma. Timely recognition and treatment is everything in such a
situation, and it needs a robust staged management pathway to optimize the chance
of limb preservation. We report a case of a motorcyclist admitted to the
department of orthopedics at Chambery hospital, France, with a complex comminuted
and open distal femoral fracture of the left leg, associated with a brachial
plexus injury to the ipsilateral upper limb. On arrival to the emergency
department, damage control stabilization and surgery was commenced, debridement
of contaminated non-viable tissue, abundant antiseptic lavage and application of
external fixation coupled with the use of antibiotic spacer. Following
normalization of inflammatory markers and ensuring no clinical signs of
infection, subsequent management consisted of joint reconstruction to achieve a
functional knee. The external fixator and femoral spacer was removed and a
modular megaprosthesis was implanted with a lateral gastrocnemius flap to cover
the exposed knee joint and reinforce the extensor apparatus. Nerve graft to the
left brachial plexus injury was performed at University Hospital of Grenoble. Our
patient entered an intensive rehabilitation program and at 1 year follow-up
achieved good knee function and sensation to the left upper limb.
PMID- 26421103
TI - Genome sequence of a native-feather degrading extremely thermophilic Eubacterium,
Fervidobacterium islandicum AW-1.
AB - Fervidobacterium islandicum AW-1 (KCTC 4680) is an extremely thermophilic
anaerobe isolated from a hot spring in Indonesia. This bacterium could degrade
native chicken feathers completely at 70 degrees C within 48 h, which is of
potential importance on the basis of relevant environmental and agricultural
issues in bioremediation and development of eco-friendly bioprocesses for the
treatment of native feathers. However, its genomic and phylogenetic analysis
remains unclear. Here, we report the high-quality draft genome sequence of an
extremely thermophilic anaerobe, F. islandicum AW-1. The genome consists of
2,359,755 bp, which encodes 2,184 protein-coding genes and 64 RNA-encoding genes.
This may reveal insights into anaerobic metabolism for keratin degradation and
also provide a biological option for poultry waste treatments.
PMID- 26421104
TI - High-resolution anoscopy: Unchartered territory for gastroenterologists?
AB - High-resolution anoscopy (HRA) is a procedure where patients with an increased
risk of anal cancer, like men who have sex with men, human immunodeficiency virus
infected individuals, transplant patients and women with a history of lower
genital tract neoplasia, with abnormal anal cytology results, are submitted to
anal and perianal visualization under magnification. This will allow for a better
detection of anal high-grade lesions that can be treated, in an effort to prevent
anal cancer. Anal cancer screening follows the same principles that cervical
cancer screening. During this procedure, an anoscope is inserted and a colposcope
is used to examine systematically the squamocolumnar junction, the transformation
zone and the perianal skin. Initially the observation is done with no staining
and then with the application of acetic acid and Lugol's iodine solution,
allowing for better lesion identification and characterization. Any suspicious
lesion seen should be carefully evaluated and biopsied. Without HRA only a small
percentage of suspicious lesions are identified. High-grade lesions that are
detected can be ablated under HRA. This is a challenging exam to perform, with a
long learning curve and the number of clinicians performing it is limited,
although the growing number of patients that need to been screened. Specific
equipment is required, with these patients ideally been followed by a
multidisciplinary team, in a reference centre. HRA remains unfamiliar for many
gastroenterologists.
PMID- 26421105
TI - Upper non-variceal gastrointestinal bleeding - review the effectiveness of
endoscopic hemostasis methods.
AB - Upper non-variceal gastrointestinal bleeding is a condition that requires
immediate medical intervention and has a high associated mortality rate
(exceeding 10%). The vast majority of upper gastrointestinal bleeding cases are
due to peptic ulcers. Helicobacter pylori infection, non-steroidal anti
inflammatory drugs and aspirin are the main risk factors for peptic ulcer
disease. Endoscopic therapy has generally been recommended as the first-line
treatment for upper gastrointestinal bleeding as it has been shown to reduce
recurrent bleeding, the need for surgery and mortality. Early endoscopy (within
24 h of hospital admission) has a greater impact than delayed endoscopy on the
length of hospital stay and requirement for blood transfusion. This paper aims to
review and compare the efficacy of the types of endoscopic hemostasis most
commonly used to control non-variceal gastrointestinal bleeding by pooling data
from the literature.
PMID- 26421106
TI - Hospitalization for esophageal achalasia in the United States.
AB - AIM: To assess the outcome of different treatments in patients admitted for
esophageal achalasia in the United States. METHODS: This is a retrospective
analysis using the Nationwide Inpatient Sample over an 8-year period (2003-2010).
Patients admitted with a primary diagnosis of achalasia were divided into 3
groups based on their treatment: (1) Group 1: patients who underwent Heller
myotomy during their hospital stay; (2) Group 2: patients who underwent
esophagectomy; and (3) Group 3: patients not undergoing surgical treatment.
Primary outcome was in-hospital mortality. Secondary outcomes included length of
stay (LOS), discharge destination and total hospital charges. RESULTS: Among
27141 patients admitted with achalasia, nearly half (48.5%) underwent Heller
myotomy, 2.5% underwent esophagectomy and 49.0% had endoscopic or other
treatment. Patients in group 1 were younger, healthier, and had the lowest
mortality when compared with the other two groups. Group 2 had the highest LOS
and hospital charges among all groups. Group 3 had the highest mortality (1.2%, P
< 0.001) and the lowest home discharge rate (78.8%) when compared to the other
groups. The most frequently performed procedures among group 3 were esophageal
dilatation (25.9%) and injection (13.3%). Among patients who died in this group
the most common associated morbidities included acute respiratory failure, sepsis
and aspiration pneumonia. CONCLUSION: Surgery for achalasia carries exceedingly
low mortality in the modern era; however, in complicated patients, even less
invasive treatments are burdened by significant mortality and morbidity.
PMID- 26421107
TI - Triradiate caecal fold: Is it a useful landmark for caecal intubation in
colonoscopy?
AB - AIM: To determine the frequency of identification of the triradiate fold during
colonoscopy and evaluate its reliability as a marker of caecal intubation.
METHODS: One hundred consecutive patients undergoing colonoscopy in a tertiary
hospital colorectal unit from May to September 2013 were studied. Video
documentation of the caecum was recorded and shown to consultant colorectal
surgeons on the unit. Each reviewer was asked through a series of questions to
independently identify the triradiate fold. The main outcome was the frequency of
visualisation of the triradiate fold in the caecum. RESULTS: The triradiate fold
was seen on average in 18% of cases, but inter-observer agreement was poor. There
were only four patients (4%) in which all reviewers agreed on the presence of a
triradiate fold. In patients who had undergone previous appendicectomy, the
appendiceal orifice was less frequently seen compared with patients who had not
undergone appendicectomy. CONCLUSION: The triradiate fold is infrequently seen
during colonoscopy and is therefore an unreliable landmark of caecal intubation.
PMID- 26421108
TI - Endoscopic ultrasound guided thrombin injection of angiographically occult
pancreatitis associated visceral artery pseudoaneurysms: Case series.
AB - Pseudoaneurysm is a known complication of pancreatitis associated with
significant mortality and morbidity. Imaging plays an important role in the
diagnosis and management. Computed tomography (CT) helps localize the lesion and
the severity of the background pancreatitis but digital subtraction angiography
with coil embolization is recommended to avoid bleeding and inadvertent surgery.
However, in cases where angiographic coil embolization is not feasible due to
technical reasons, thrombin injection via CT or ultrasound guidance remains a
viable option and often described in literature. In this series, effort has been
made to highlight the role of endoscopic ultrasound guided thrombin instillation
especially in patients with poorly visualized pseudoaneurysm on ultrasound
thereby avoiding surgery and the associated mortality and morbidity.
PMID- 26421109
TI - Medical Errors: Why Now and What's Next?
PMID- 26421110
TI - Applicability of the Existing CVD Risk Assessment Tools to Type II Diabetics in
Oman: A Review.
AB - Patients with type II diabetes (T2DM) have an elevated risk for cardiovascular
disease (CVD), and it is considered to be a leading cause of morbidity and
premature mortality in these patients. Many traditional risk factors such as age,
male sex, hypertension, dyslipidemia, glycemic control, diabetes duration, renal
dysfunction, obesity, and smoking have been studied and identified as independent
factors for CVD. Quantifying the risk of CVD among diabetics using the common
risk factors in order to plan the treatment and preventive measures is important
in the management of these patients as recommended by many clinical guidelines.
Therefore, several risk assessment tools have been developed in different parts
of the world for this purpose. These include the tools that have been developed
for general populations and considered T2DM as a risk factor, and the tools that
have been developed for T2DM populations specifically. However, due to the
differences in sociodemographic factors and lifestyle patterns, as well as the
differences in the distribution of various CVD risk factors in different diabetic
populations, the external applicability of these tools on different populations
is questionable. This review aims to address the applicability of the existing
CVD risk models to the Omani diabetic population.
PMID- 26421111
TI - Stopping Oxytocin in Active Labor Rather Than Continuing it until Delivery: A
Viable Option for the Induction of Labor.
AB - OBJECTIVE: Induction of labor (IOL), using intravenous oxytocin, is the
artificial initiation of labor before its spontaneous onset for the purpose of
delivery of the fetoplacental unit. Although there are various studies looking at
dosages of oxytocin, only a few have addressed the issue of discontinuation of
oxytocin in the active stage of labor. Thus, our study was conducted to evaluate
the need for continuation versus discontinuation of oxytocin during active labor.
METHODS: This prospective, randomized controlled trial included 106 women who
needed IOL. Oxytocin infusion was initiated at a rate of 3mIU/min and was
incremental until 4-6cm cervical dilation. At this point the patients were
randomly assigned into one of two groups. In group one, oxytocin was
discontinued, and infusion was continued with 0.9% sodium chloride solution. In
group two, oxytocin was continued at the same dose until delivery. RESULTS: The
duration of oxytocin infusion was 5.5 hours in the oxytocin discontinuation group
and 11.0 hours in oxytocin continuation group (p<0.001). The total dose of
oxytocin was significantly higher in group two (6.1 units vs. 16.5 units;
p=<0.001). The induction-delivery interval was significantly less in group one
(9.1 and 11.2 hours in group one and group two, respectively; p=0.023).
CONCLUSION: Oxytocin discontinuation in the active stage of labor did not prolong
the active stage. The total duration of labor and total oxytocin dose were
significantly less in the oxytocin discontinuation group. Our results suggest
that oxytocin discontinuation is an alternative and viable option particularly in
resource poor and economically challenged settings. It not only reduces the need
for intense monitoring and prolonged oxytocin use-associated dangers but reduces
the total cost of labor management.
PMID- 26421112
TI - Association of Hyperglycemia with In-Hospital Mortality and Morbidity in Libyan
Patients with Diabetes and Acute Coronary Syndromes.
AB - OBJECTIVE: Hyperglycemia on admission and during hospital stay is a well
established predictor of short-term and long-term mortality in patients with
acute myocardial infarction. Our study investigated the impact of blood glucose
levels on admission and in-hospital hyperglycemia on the morbidity and mortality
of Libyan patients admitted with acute coronary syndromes (acute myocardial
infarction and unstable angina). METHODS: In this retrospective study, the
records of patients admitted with acute coronary syndrome to The 7th Of October
Hospital, Benghazi, Libya, between January 2011 and December 2011 were reviewed.
The level of blood glucose on admission, and the average blood glucose during the
hospital stay were recorded to determine their effects on in-hospital
complications (e.g. cardiogenic shock, acute heart failure, arrhythmias, and/or
heart block) and mortality. RESULTS: During the study period, 121 patients with
diabetes were admitted with acute coronary syndrome. The mortality rate in
patients with diabetes and acute coronary syndrome was 12.4%. Patients with a
mean glucose level greater than 200mg/dL had a higher in-hospital mortality and a
higher rate of complications than those with a mean glucose level <=200mg/dL
(27.5% vs. 2.6%, p<0.001 and 19.7% vs. 45.5%, p=0.004, respectively). There was
no difference in in-hospital mortality between patients with a glucose level at
admission <=140mg/dL and those admitted with a glucose level >140mg/dL (6.9% vs.
14.3%; p=0.295), but the rate of complications was higher in the latter group
(13.8% vs. 34.1%; p=0.036). Patients with admission glucose levels >140mg/dL also
had a higher rate of complications at presentation (26.4% vs. 6.9%; p=0.027).
CONCLUSION: In patients with diabetes and acute coronary syndrome, hyperglycemia
during hospitalization predicted a worse outcome in terms of the rates of in
hospital complications and in-hospital mortality. Hyperglycemia at the time of
admission was also associated with higher rate of complications particularly at
the time of presentation.
PMID- 26421113
TI - Sociodemographic and Clinical Determinants of Time to Care-Seeking Among Febrile
Children Under-Five in North-Central Nigeria.
AB - OBJECTIVES: Our study sought to determine the time parents of febrile children
under the age of five took to seek competent medical care. We also looked at the
possible sociodemographic/ clinical factors that influenced this presentation.
METHODS: Four hundred and nine under-fives presenting at the emergency unit with
a history of fever in the last 48 hours along with their mothers were recruited
over four months. Relevant sociodemographic information as well as symptoms and
duration of illness were obtained. Multinomial regression analysis was performed
to determine the predictors of early and late presentation. RESULTS: Over half
(57%) of patients presented within 24 hours of onset of fever. The mean age of
the children and mothers were 22+/-15 months and 30+/-5 years, respectively. High
social class (odds ratio (OR) 6.5, 95% CI 1.6-26.4), Hausa ethnic group (OR 19.3,
95% CI 5.7-65.6), convulsions (OR 3.2, 95% CI 1.6-6.5) and appearance of other
symptoms (OR 6.0, 95% CI 3.0-12.0) were significant predictors of early
presentation. Secondary school education, belonging to another ethnic group, and
non-resolution of fever were significant predictors of late presentation.
CONCLUSION: The majority of febrile under-fives came to the hospital to seek
competent medical care within the first 24 hours of illness. However, there is a
need for more parental education on early hospital presentation for parents of
low socioeconomic status and educational background.
PMID- 26421114
TI - A Comparison of Continuous Subcutaneous Insulin Infusion vs. Multiple Daily
Insulin Injection in Children with Type I Diabetes in Kuwait: Glycemic Control,
Insulin Requirement, and BMI.
AB - OBJECTIVE: Continuous subcutaneous insulin infusion (CSII) and multiple daily
insulin injections (MDI) are two methods currently used to manage type I diabetes
mellitus (T1DM). Here we compare our experiences with CSII and MDI in a large
cohort of pediatric patients in Kuwait. METHODS: Data on 326 patients with T1DM
who were started on CSII between 2007 and 2012 were retrospectively compared with
those of 326 patients on MDI. They were matched for sex, age at diagnosis, T1DM
duration, glycemic control, insulin requirement, and body mass index (BMI). Data
were collected at baseline and every three months and included glycated
hemoglobin (HbA1c), insulin dose, and adverse events (severe hypoglycemia,
diabetic ketoacidosis, and skin problems). RESULTS: The main reason for switching
to CSII was to achieve better glycemic control (37%), followed by reducing
hypoglycemia, and improving the quality of life (13.3% each). Although HbA1c
decrease was most significant in the first year, it continued to be significantly
lower in the CSII group compared to the MDI throughout the study period. Total
daily insulin requirements were significantly lower in the CSII group. BMI
increased in both groups, but the difference was significant only at the end of
the fifth year. There was no significant change in the rate of diabetic
ketoacidosis in either group. The CSII patients had more severe hypoglycemic
episodes at baseline; however, it significantly decreased throughout the study
period. Only five patients discontinued CSII therapy and two of these restarted
within three months. CONCLUSION: CSII is a safe intensive insulin therapy in
youngsters with T1DM and achieved markedly fewer severe hypoglycemic episodes and
lower daily insulin requirements.
PMID- 26421115
TI - Survival Impact of Secondary Cytoreductive Surgery for Recurrent Ovarian Cancer
in an Asian Population.
AB - OBJECTIVE: The aim of this study was to evaluate the role of secondary
cytoreductive surgery in Asian patients with recurrent ovarian cancer and to
assess prognostic variables on overall post-recurrence survival time. METHODS: We
conducted a retrospective review of patients with recurrent ovarian cancer who
underwent secondary cytoreduction at the Gynaecological Cancer Center at the KK
Women's and Children's Hospital, Singapore, between 1999 and 2009. Eligible
patients included those who had been firstly treated by primary cytoreductive
surgery and followed by adjuvant chemotherapy and had a period of clinical
remission of at least six months and subsequently underwent secondary
cytoreductive surgery for recurrence. Univariate analysis was performed to
evaluate various variables influencing the overall survival. RESULTS: Twenty-five
patients met our eligibility criteria. The median age was 52 years (range=31-78
years). The median time from completion of primary treatment to recurrence was
25.1 months (range=6.4-83.4). Secondary cytoreduction was optimal in 20 of 25
patients (80%). The median follow-up duration was 38.9 months (range=17.8-72.4)
and median overall survival time was 33.1 months (95% confidence interval, 15.3
undefined.). Ten (40.0%) patients required bowel resection, but no end colostomy
was performed. One (4.0%) patient had wedge resection of the liver, one (4.0%)
had a distal pancreatectomy, one (4.0%) had a unilateral nephrectomy, and one
(4.0%) had adrenalectomy. There were no operative deaths. The overall survival of
patients who responded to secondary cytoreductive surgery and adjuvant
chemotherapy was significantly longer than those patients who did not respond to
the treatment. Of those patients who responded to the surgical management,
patients with clear cell carcinoma fared well compared to those with the
endometrioid, mucinous adenocarcinoma, and papillary serous type (p<0.001).
Complete secondary cytoreductive surgery appeared to have some relationship to
overall survival but was not statistically significant. CONCLUSION: In carefully
selected patients with recurrent ovarian cancer, optimal cytoreductive surgery is
possible and in a subgroup of patients who respond to surgery and chemotherapy
survival is significantly longer.
PMID- 26421116
TI - The Valuable Role of Measuring Serum Lipid Profile in Cancer Progression.
AB - OBJECTIVE: Serum lipid levels are not only associated with etiology, but also
with prognosis in cancer. To investigate this issue further, we aimed to evaluate
the serum levels of lipids in association with the most important prognostic
indicators in cancer patients at the start of chemotherapy. METHODS: In a
retrospective cross-sectional study, using existing medical records obtained from
2009-2014, the data of all incident cancer cases in Iranian patients referred to
the Semnan oncology clinic for chemotherapy were analyzed. Data on demographics,
cancer type, prognostic indicators (e.g. lymph node involvement, metastasis, and
stage of disease), as well as the patient's lipid profile were collected. We used
multiple logistic regression models to show the relationship between prognosis
indicators and lipid profile adjusting for age, gender, and type of cancer.
RESULTS: The data of 205 patients was gathered. We found a significant difference
in the lipid profile between different types of cancers (breast, colon, gastric,
and ovarian). With the exception of high-density lipoprotein levels in women,
which were higher than in men, the means of other lipid profiles were similar
between the genders. There was a significant association between higher levels of
low-density lipoprotein (LDL >110mg/dL) in the serum and metastasis (adjusted
odds ratio=2.4, 95% CI 1.2-3.5). No significant association was reported between
lipid profile and lymph nodes involvement and stage of the disease. CONCLUSION:
Our study suggested a benefit of measuring serum levels of lipids for predicting
cancer progression. Increased LDL levels can be considered a predictive factor
for increasing the risk of metastasis.
PMID- 26421117
TI - Prevalence of Chronic Suppurative Otitis Media (CSOM) and Associated Hearing
Impairment Among School-aged Children in Yemen.
AB - BACKGROUND: Chronic suppurative otitis media (CSOM) is one of the leading causes
of preventable disabling hearing impairment (DHI) in developing countries. Early
detection and management complements advances made in other survival programs,
improves work capacity, and enhances learning opportunities for school children.
We aimed to determine the prevalence of CSOM and associated DHI among school
children aged six to 16 years in Socotra Island, Yemen. METHODS: We conducted a
cross-sectional community-based survey, from 20 April 2011 to 20 June 2011. The
study procedures involved completing a questionnaire, an otoscopic ear
examination, an audiometric test of hearing, and tuning fork tests for the type
of DHI. RESULTS: A total of 686 children were interviewed and examined for CSOM
and associated DHI of CSOM cases. The prevalence of CSOM was 7.4%, (95% CI 5.5
9.4). CSOM status was significantly associated with DHI (p=0.001), but no
significant associations were found between demographic characteristics and CSOM
status. Logistic regression identified four significant independent contributing
factors: history of ear discharge in the last 12 months (odds ratio (OR) 7.8, 95%
CI 3.9-15.6); swimming in local pools (OR 6.0, 95% CI 1.4-25.4); recurrent
respiratory tract infection more than three times per year (OR 5.3, 95% CI 2.5
11.0); and overcrowding with more than three families per house (OR 4.4, 95% CI
1.7-11.5). . CONCLUSION: The burden of CSOM in the children studied indicates a
high level of DHI in these communities within Yemen. A history of ear discharge,
swimming in local pools, recurrent respiratory infections, and overcrowded
housing were the strongest predictors for CSOM. There is a need for better ear
care and screening programs for early detection and management of this disease.
PMID- 26421118
TI - Non-steroidal Anti-inflammatory Drugs (NSAIDs) Use in Primary Health Care Centers
in A'Seeb, Muscat: A Clinical Audit.
AB - OBJECTIVE: We sought to assess the trend of non-steroidal anti-inflammatory drug
(NSAID) use in primary health care institutions located in A'Seeb, a province in
the capital city of Oman, Muscat. Additionally, we evaluated the relationship
between a physician's years of experience and the number of prescription issued,
as well as the presence of risk factors and side effects in the patients who
received these prescriptions. METHOD: A clinical audit was conducted in four
primary health care centers in the Muscat region over a one-week period in April
2014. The target population included patients aged 18 years or over who attended
one of the four health centers and were prescribed NSAIDs. Overall, 272 patients
were recruited by systematic random sampling. The data were collected by two
methods: direct face-to-face interviews and evaluations of the patient's
electronic medical file. The prescribing doctors were blind to the audit. The
collected information included patients demographics, past and current medical
history of related comorbidities, NSAID type, dose, duration and indications for
use, concomitant warfarin or/and aspirin prescriptions, and co-prescription of
gastroprotective agents. RESULTS: In total, 15% of patients received an NSAID
prescription: females were issued more prescriptions than males. The percentage
of patients who received an NSAID prescription across the health centers ranged
from 9% to 24%. The main reason for prescribing NSAIDs was musculoskeletal
problems. The most frequently prescribed NSAID was ibuprofen. Sixteen percent of
patients who received an NSAID prescription had a risk factor related to its use.
The mean and median duration of the NSAID prescriptions of all types were 5.6 and
5.0 days, respectively. Physicians with a greater number of years experience
prescribed more NSAIDs. CONCLUSION: Our study showed that the number of
prescriptions of NSAIDs among various institutes varied, which could reflect the
level of awareness concerning NSAID risks among the prescribing doctors. NSAIDs
were prescribed for patients with comorbidities and patients with previously
documented side effects without considering protective agents. Therefore, we
suggest that the use of these medications is controlled, especially in high-risk
populations.
PMID- 26421119
TI - Unusual Cause of Swelling in the Upper Limb: Kimura Disease.
AB - Kimura disease is a rare chronic inflammatory disease of unknown etiology. The
disease typically presents in young Asian males with single or multiple slowly
progressing painless subcutaneous lumps in the head and neck region; regional
lymphadenopathy is commonly accompanied. The disease is associated with
peripheral blood eosinophilia and elevated serum immunoglobulin E levels. This
gives an important clinical clue to the diagnosis and implies a possible immune
mediated pathophysiology. Although the disease commonly affects the head and neck
region, it may also affect the extremities, axilla, groin, and abdomen. Upper
limb involvement in Kimura's disease is rare and few cases have been reported in
the literature. We describe the case of a man who presented with a history of
progressive upper limb swelling. He was diagnosed with Kimura's disease based on
concordant clinical, laboratory, radiological, and histopathological grounds.
Although rare in the upper limb, the possibility of Kimura's disease has to be
considered in young males presenting with painless swelling in the medial
epitrochlear region with compatible imaging appearance, particularly if
associated with lymph node enlargement and increased blood eosinophils.
Characteristic imaging findings of Kimura's disease of the upper limb include
specific location along the neuro-lymphovascular structures, the absence of
necrosis or calcification, mutliple flow voids representing vascular structures,
a varying amount of edema of subcutaneous fat plane overlying the lesion;
displacement of adjacent muscles; and neurovascular structures without signs of
direct invasion. Clinicians should be aware of this distinct entity in order to
avoid misdiagnosis and to tailor appropriate management.
PMID- 26421120
TI - Dermatofibrosarcoma Protuberans: A Rare Malignancy of the Breast.
AB - Dermatofibrosarcoma protuberans (DFSP) of the breast is a rare skin cancer with
only a few cases reported in the literature. It corresponds to approximately 1%
of all soft tissue sarcomas and to less than 0.1% of all malignancies with annual
incidence of 0.8-4.5 cases per million. DFSP usually affects young and middle
aged adults and it can affect any site, but most commonly the trunk and
extremities. This tumor arises from the deep dermis and subcutaneous tissues and
is usually locally aggressive, but rarely metastasizes. Surgery including wide
local excision with free margins remains the main modality of treatment. We
report a case in a 28-year-old Omani woman who presented with a right breast lump
to a local secondary hospital. She was offered excision biopsy of the lump and
the histology came as DFSP with involved margins. The patient was then referred
to the Breast Unit at the Royal Hospital where she was reviewed by
multidisciplinary team including breast surgeons, oncologists, radiation
oncologists, pathologists, and breast radiologists. Her laboratory and
radiological investigations did not show any signs of distal metastasis and
breast ultrasound did not reveal any residual breast lesions. We performed a wide
re-excision of the previous surgical scar with the underlying breast tissues down
to the level of the pectoral fascia followed by treatment with radiotherapy. The
final histology report showed the presence of a 4*5mm residual tumor, and all
resection margins were tumor-free. At six months follow-up, she had no signs of
local recurrence. We publish this case report because of its rarity.
PMID- 26421121
TI - A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical
Presentation: ?A Case Report and Literature Review.
AB - A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital,
Oman with right upper abdominal pain and backache that had lasted 10 days. She
had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The
patient's history revealed that she had a similar incidence of abdominal pain two
months prior, which was a "dull ache" in nature and somewhat associated with
headache. The pain was relieved using a mild analgesic drug. Abdominal
ultrasonography showed a right adrenal mass, and both computed tomography and
magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass
consistent with adrenal pheochromocytoma. However, clinical biochemistry tests
revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and
epinephrine) and metanephrine, which are unusual findings in adrenal
pheochromocytoma. Meanwhile, the patient had markedly raised plasma
normetanephrine (10-fold) which, together with the normal metanephrine,
constitutes a metabolic profile that is compatible with extra-adrenal
pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold),
consistent with the presence of a neuroendocrine tumor. Laparoscopic right
adrenalectomy was done and the adrenal tumor was excised and retrieved in total.
Histopathology and immunohistochemistry confirmed the diagnosis of adrenal
pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin,
and S-100 protein. Following surgery, the patient did well and showed full
recovery at follow-up after three months. Molecular genetic testing showed no
pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC,
SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the
pathophysiology and any previous reports of such case. To our knowledge, this is
the first report in Oman of the extremely rare entity of pheochromocytoma with an
unusual clinical and biochemical scenario.
PMID- 26421122
TI - Ensuring Clinical Competence in Oman.
PMID- 26421123
TI - Right-sided Pleuritic Chest Pain in a 36-year-old Male.
PMID- 26421124
TI - Nasopharyngeal Carcinoma in Oman and Malaysia: Is There Any Difference?
PMID- 26421125
TI - Letter in Reply: Comparing Nasopharyngeal Carcinoma in Oman and Malaysia.
PMID- 26421126
TI - Epidemiology of Cyclospora Species in Humans in Malatya Province in Turkey.
AB - BACKGROUND: Cyclospora species are rare among other Coccidia parasites and can
cause recurrent gastroenteritis. Cyclospora spp. can infect reptiles, insects,
rodents, and mammals. OBJECTIVES: The present study aimed to determine the
epidemiology of Cyclospora spp. in Malatya province and its neighboring
provinces. PATIENTS AND METHODS: Totally, 2281 stool samples taken from patients
with digestive system complaints who referred to the polyclinics affiliated with
Inonu University, Faculty of Medicine in Malatya Province and its neighboring
provinces, in 2006, and whose stool specimens were submitted to the parasitology
department were examined. A questionnaire was developed to determine the
epidemiology of Cyclospora spp. in the patients as the dependent variable of the
study. All the participants signed an informed written consent. The samples were
coated with EntellanTM after staining via acid-fast staining and were examined on
an immersion microscope objective. The data are presented as mean, standard
deviation, or number/percentage. The chi-square test was used for the statistical
analyses. Statistically, a P value < 0.05 was accepted as meaningful. RESULTS:
The stool samples were examined via direct microscopic examination and acid-fast
staining. Positivity was determined in 129 (5.7%) cases. In the overall
assessment of the patients with respect to general body itching, rectal itching,
allergy, immunosuppression plus cancer, shortness of breath, ulcerative colitis,
diarrhea, abdominal pain, salivation, constipation, nausea, vomiting, growth
retardation, and anemia, there was no significant relationship. However, in the
statistical evaluations among the positive cases, the difference was found to be
significant. CONCLUSIONS: The study was conducted in Malatya Province, but
patients from the neighboring provinces were also included in the evaluation
during the study. Of all the positive cases, 5.6% were those from Malatya
Province and its surrounding areas. Additionally, Cyclospora spp. were observed
among the patients referring to the polyclinics with digestive system complaints
in 8.1% of those from the Adiyaman province and in 6.9% of those from the
Kahramanmaras region. The incidence of Cyclospora cayetanensis may be higher in
these regions if an epidemiological study is performed. Consequently, we suggest
that Cyclospora spp. be investigated in digestive system disorders, especially in
immunosuppressed patients.
PMID- 26421127
TI - Use of Padlock Probes and Rolling Circle Amplification (RCA) for Rapid
Identification of Trichophyton Species, Related to Human and Animal Disorder.
AB - BACKGROUND: The high degree of phenotypic similarity among Trichophyton species
makes their identification difficult. OBJECTIVES: The current study aims to
establish the use of rolling circle amplification (RCA) based on internal
transcribed spacer ribosomal DNA (ITS rDNA) as a powerful, simple, and rapid
procedure for distinguishing closely related organisms, and specifically to
identify Trichophyton species, which cause human and animal disorders. MATERIALS
AND METHODS: A total of sixty-one isolates belonging to three species of
Trichophyton were identified to the species level based on microscopic and
macroscopic examinations and their ITS rDNA regions were sequenced. Three
specific circular oligonucleotide probes targeting the ITS1 and ITS2 regions were
designed to differentiate Trichophyton rubrum, T. mentagrophytes, and T.
tonsurans. RESULTS: Of the 61 putative Trichophyton clinical isolates, 52 were
identified to the species level. The most common species was T. mentagrophytes
var. interdigitale (31 isolates), followed by T. rubrum (11 isolates), T.
tonsurans (9 isolates), and T. violaceum (1 isolates); moreover, 9 isolates were
identified as non-Trichophyton species. The RCA method correctly identified four
Trichophyton species and was 100% specific for each species. Neither cross
reaction between the examined species of Trichophyton nor false positive or false
negative results were observed. CONCLUSIONS: Species identification of
Trichophyton is crucially important for epidemiological and phylogenetic purposes
and for genotype delineation. RCA based on ITS polymorphisms can be used to
generate identification barcodes and as an alternative to DNA sequencing; it is a
very fast, specific, and economical tool for species identification.
PMID- 26421128
TI - Dissemination of Extended-Spectrum beta-Lactamases and Quinolone Resistance Genes
Among Clinical Isolates of Uropathogenic Escherichia coli in Children.
AB - BACKGROUND: Urinary tract infection (UTI) is one of the most common childhood
bacterial infections and Escherichia coli is the major pathogen. Producing beta
lactamase enzymes are the most common mechanism of bacterial resistance.
OBJECTIVES: This study aimed to determine the prevalence of Extended-Spectrum
beta-Lactamases (ESBLs) and Quinolone Resistance (qnr) genes in E. coli strains
isolated from UTIs. MATERIALS AND METHODS: In this study, a total of 120 isolates
of E. coli from urinary tract infections of the children were collected at Besat
Hospital in Hamadan, Iran, from October 2010 to October 2011. The bacterial
isolates were identified by standard biochemical methods. Antimicrobial
susceptibilities were determined by disk diffusion method, and ESBLs-producing
was confirmed phenotypically using the double-disk synergy (DDS) test. The
presence and identification of ESBLs and qnr genes were determined by Polymerase
Chain Reaction (PCR). RESULTS: The highest sensitivity was seen to imipenem
(96.7%), amikacin (92.5%), nitrofurantoin (93.3%), ofloxacin (81.7%), gentamicin
norfloxacin (70.8%), and ciprofloxacin (79.2%). In contrast, the highest rate of
resistance was seen to co-trimoxazole (77%) and nalidixic acid (40.9%). The
results showed that 6 (2.18%) and 4 (1.12%) isolates of ESBL-producing E. coli
were positive with respect to having qnrB and qnrS genes, respectively. No
isolates was found to have qnrA. CONCLUSIONS: CTX-M was the most prevalent ESBL
genotype in uropathogenic E. coli (UPEC) isolated from UTI. In addition, a high
frequency of qnr genes among ESBL-producing E. coli was identified in this study.
In order to avoid treatment failures, we recommend using phenotypic and molecular
methods to diagnose these enzymes and qnr genes.
PMID- 26421129
TI - Characteristics and Antibiotic Resistance of Urinary Tract Pathogens Isolated
From Punjab, Pakistan.
AB - BACKGROUND: Urinary tract infection (UTI) is deemed the most prevalent infectious
disease in that it has now touched the overall incidence of 18/1000 persons per
year in the general population. OBJECTIVES: This study sought to determine the
characteristics of isolates from patients with UTI and their susceptibility to
commonly used antibiotics in Punjab, Pakistan. PATIENTS AND METHODS: Totally,
1429 urine samples were analyzed from UTI patients for the isolation of
uropathogens at Chughtai's Lahore Lab, Lahore, Pakistan, during a period of 14
months. The antimicrobial susceptibility test was performed via the disc
diffusion method for the isolates obtained from 392 (26%) positive cultures.
RESULTS: The highest percentage (67%) of isolates was from females in comparison
to males (33%). The frequency of Escherichia coli was the highest (62%) in
culture-positive urine samples, followed by E. faecalis (15%), Candida (14%),
Pseudomonas (6%), Klebsiella spp. (1%), Proteus (1%), and Staphylococcus aureus
(1%). E. coli was highly resistant to antimicrobial drugs, viz. cephalexin (95%),
cephradine (95%), pipemidic acid (92%), amikacin (91%), and nalidixic acid (91%).
Most of the routine beta-lactam antibiotics like amoxicillin/clavulanic acid,
ampicillin, and aztreonam were also ineffective against E. coli, with resistance
rates of 84%, 84%, and 72%, correspondingly. This pathogen showed maximum
susceptibility (97%) against three drugs, namely imipenem, meropenem, and
cefoperazone. Piperacillin and fosfomycin also provided significant results
against E. coli with respective susceptibility rates of 96% and 90%. CONCLUSIONS:
Our results showed that broad-spectrum antibiotics such as imipenem, meropenem,
fosfomycin, cefoperazone/sulbactam, and vancomycin would be the first line and
the most effective drugs for the empirical treatment of urinary tract pathogens
due to their higher resistance rates against other drugs like cephalexin,
cephradine, ciprofloxacin, levofloxacin, and norfloxacin.
PMID- 26421130
TI - Seroprevalence of Hepatitis A and E Virus Infections Among Healthy Population in
Shiraz, Southern Iran.
AB - BACKGROUND: Enterically-transmitted acute viral hepatitis is caused predominantly
by hepatitis A virus (HAV) and hepatitis E virus (HEV). The prevalence of HEV and
HAV infections varies in different geographical regions. OBJECTIVES: This study
was conducted to determine the prevalence of HEV and HAV infections among Iranian
healthy individuals in southern Iran. PATIENTS AND METHODS: Totally, 1030 samples
were collected from healthy subjects in schools, those referred to tertiary
outpatient clinics and health centers in Shiraz between November 2011 and May
2012. Their ages ranged between six months and 95 years. The presence of total
anti-HAV and anti-HEV immunoglobulin M (IgM) in plasma was assessed by ELISA.
RESULTS: The results showed that 66.2% and 0.6% of the general population in this
area were positive for total anti-HAV and IgM antibodies by ELISA, respectively.
As seen, 13.4% and 0.9% were positive for total anti-HEV and IgM antibodies,
respectively. The difference in total anti-HAV and anti-HEV antibodies was
significant among the age groups (P < 0.001). CONCLUSIONS: This study showed that
the prevalence rates of HAV and HEV antibodies were positively correlated with
age. The results demonstrated that the infection with these two viruses in the
region was high and some high-risk individuals including females at child-bearing
age were more susceptible. HAV vaccination could be recommended for antibody
negative adults.
PMID- 26421131
TI - Biochemical Fingerprinting of Methicillin-Resistant Staphylococcus aureus
Isolated From Sewage and Hospital in Iran.
AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is known as a
common pathogen in nosocomial and community-acquired infections. Sewage acts as
an environmental reservoir and may have a significant role in development and
dissemination of antibiotic resistance. OBJECTIVES: This study was undertaken to
determine the epidemiological relatedness between the MRSA isolated from sewage
and human infections. MATERIALS AND METHODS: Samples were collected from a
referral hospital and also a sewage treatment plant in Tehran, Iran, during 2010.
All the MRSA isolates were identified at the species level and typed using Phene
plate (PhP) system and SCCmec typing. Antibiotic susceptibility tests were also
performed. RESULTS: Of the 1142 isolates, 200 MRSA strains from the sewage (n =
100) and the clinic (n = 100) were isolated. Distinct PhP types, consisting of 16
common types and 13 single types, and also 3 different staphylococcal cassette
chromosome mec (SCCmec) types (III, IVa and IVc) were found amongst the MRSA
isolated from the two different sources. The results of antibiotic susceptibility
testing showed an increased resistance to penicillin, ciprofloxacin,
erythromycin, clindamycin and tetracycline. In addition, none of the isolates
showed resistance to vancomycin, quinupristin -dalfopristin and linezolid.
CONCLUSIONS: The presence of common PhP types and also SCCmec type III, as an
indicator for hospital strains, among the isolates, may indicate an
epidemiological link between clinical and sewage MRSA isolates in Tehran.
PMID- 26421132
TI - Sulfonamide Resistance Genes (sul) M in Extended Spectrum Beta Lactamase (ESBL)
and Non-ESBL Producing Escherichia coli Isolated From Iranian Hospitals.
AB - BACKGROUND: Extensive use of cotrimoxazole has been associated with increasing
level of Escherichia coli resistance. OBJECTIVES: In the current study, we
focused on assessing the prevalence of E. coli resistance to cotrimoxazole and
frequency of its associated genes. MATERIALS AND METHODS: One-hundred and forty
four E. coli isolates were identified during March 2007 to April 2012 at Ilam
hospitals and Milad (Tehran) hospital. Antibiotic susceptibility for screening of
resistance isolates was done by the Kirby-Bauer method. The sul1, sul2, sul3,
dfrA1, dfrA5, int1, blaTEM, blaSHV and CTX-M genes were detected by polymerase
chain reaction (PCR) amplification. Plasmid curing was done for identifying
correlations between resistance genes and plasmids. RESULTS: Amongst the 144 E.
coli isolates, seventy-two (50%) Extended Spectrum Beta Lactamase (ESBL)
producing and seventy-two (50%) non-ESBL-producing E. coli isolates were
identified; eighty-seven isolates (60.41%) were resistant to cotrimoxazole.
Frequencies of sul1, sul2 and sul3, were 81% (116 isolates), 67% (96 isolates)
and 2.29% (three isolates), respectively. Furthermore, 50.57% (72 isolates) had
sul1 and sul2, 2.29% (3 isolates) contained sul2 and sul3, and 2.29% (three
isolates) contained sul1, sul2 and sul3 genes, simultaneously. Thirty-four
(39.1%) of the isolates had the dfrA1 gene. Five (5.7%) of the isolates had the
dfrA5 gene. Sixty-eight (78.2%) strains contained the int1 gene. Furthermore,
dfrA1 and dfrA5 were present in three (3.4%) of the isolates. The results showed
that of the ESBL-producing isolates, 85.2% (n = 122), 53.2% (n = 76) and 26.1% (n
= 37) were blaTEM, blaSHV and CTX-M harboring isolates, respectively.
CONCLUSIONS: Our study indicated a high frequency of cotrimoxazole resistance
gene in E. coli isolates from Ilam and Tehran (Milad) hospitals, and sul genes
had a major role in cotrimoxazole resistance of these isolates.
PMID- 26421133
TI - Antibiotic Susceptibility Pattern of Aerobic and Anaerobic Bacteria Isolated From
Surgical Site Infection of Hospitalized Patients.
AB - BACKGROUND: Surgical Site Infections (SSIs) are infections of incision or deep
tissue at operation sites. These infections prolong hospitalization, delay wound
healing, and increase the overall cost and morbidity. OBJECTIVES: This study
aimed to investigate anaerobic and aerobic bacteria prevalence in surgical site
infections and determinate antibiotic susceptibility pattern in these isolates.
MATERIALS AND METHODS: One hundred SSIs specimens were obtained by needle
aspiration from purulent material in depth of infected site. These specimens were
cultured and incubated in both aerobic and anaerobic condition. For detection of
antibiotic susceptibility pattern in aerobic and anaerobic bacteria, we used disk
diffusion, agar dilution, and E-test methods. RESULTS: A total of 194 bacterial
strains were isolated from 100 samples of surgical sites. Predominant aerobic and
facultative anaerobic bacteria isolated from these specimens were the members of
Enterobacteriaceae family (66, 34.03%) followed by Pseudomonas aeruginosa (26,
13.4%), Staphylococcus aureus (24, 12.37%), Acinetobacter spp. (18, 9.28%),
Enterococcus spp. (16, 8.24%), coagulase negative Staphylococcus spp. (14, 7.22%)
and nonhemolytic streptococci (2, 1.03%). Bacteroides fragilis (26, 13.4%), and
Clostridium perfringens (2, 1.03%) were isolated as anaerobic bacteria. The most
resistant bacteria among anaerobic isolates were B. fragilis. All Gram-positive
isolates were susceptible to vancomycin and linezolid while most of
Enterobacteriaceae showed sensitivity to imipenem. CONCLUSIONS: Most SSIs
specimens were polymicrobial and predominant anaerobic isolate was B. fragilis.
Isolated aerobic and anaerobic strains showed high level of resistance to
antibiotics.
PMID- 26421134
TI - The Dynamic of Staphylococcus aureus Nasal Carriage in Central Iran.
AB - BACKGROUND: Nasal carriage of Staphylococcus aureus plays an important role in
the pathogenesis of staphylococcal infections. Anterior nasal region is a primary
origin of S. aureus. In longitudinal studies, three types of S. aureus nasal
carriers can be distinguished: persistent carriers, intermittent or transient
carriers, and noncarriers. OBJECTIVES: This study was designed to determine the
dynamic of S. aureus nasal carriage in healthy carriers of central Iran. PATIENTS
AND METHODS: A total of 813 healthy adults were subjected to this cross-sectional
study from November 2011 to January 2012 in Arak University of Medical Sciences.
Two anterior nasal swabs were taken with a week interval from each participant.
All the isolates were identified as S. aureus phenotypically by standard
laboratory methods. The isolates were reconfirmed by amplification of sa442 gene
as the identification marker. All the isolates were screened for the presence of
the PVL (Panton-Valentine leukocidin) virulence genes and arginine catabolic
mobile element (ACME-arc). RESULTS: Among the 813 subjects screened, 83 (10.2%)
were persistent carriers, 86 (10.6%) were transient carriers and 644 (79.2%)
cases were found as noncarriers. A total of 169 (20.8%) participants had
colonized S. aureus. The frequency of ACME-arc A and PVL genes in S. aureus
strains were 17% and 20%, respectively. CONCLUSIONS: Carriage of PVL-positive S.
aureus is common in this region, even in the low frequency of MRSA colonization.
The detection of ACME-arcA gene in S. aureus isolates is a public-health concern
and demands continued surveillance and close monitoring.
PMID- 26421135
TI - Antibiotic Sensitivity of Clostridium perfringens Isolated From Faeces in Tabriz,
Iran.
AB - BACKGROUND: Clostridium perfringens, a Gram-positive, anaerobic bacterium that
produces at least 16 virulence factors including 12 toxins (alpha-nu),
enterotoxin, hemolysin and neuraminidase, can create variable pathogenic
condition, ranging from a food poisoning to life-threatening myonecrosis. Among
C. perfringens strains, resistance to the drug choices such as penicillin as well
as to alternatives of penicillin like metronidazole and clindamycin has also been
observed. OBJECTIVES: The aim of this study was to determine the resistance of
isolated toxigenic and non-toxigenic C. perfringens strains against common
antimicrobial agents. MATERIALS AND METHODS: In this descriptive study, a total
of 136 stool specimens were collected. At first, cooked meat medium enrichment
method was performed on samples at 45 degrees C. Thereafter, a loopful of the
enriched culture was transferred to blood agar and incubated anaerobically at 37
degrees C for 24-72 hours. Colonies with double zone of hemolysis were identified
by different biochemical tests such as phospholipase C (lecithinase) test, indole
and urease production. The Minimum Inhibitory Concentration (MIC) for common
antibiotics was determined by Etests (Epsilometer) and duplex Polymerase Chain
Reaction (PCR) reaction was performed with specific primers for amplification of
cpe (426 bp) and plc (283 bp) Genes. RESULTS: Of 136 stool samples including
diarrhea [48] and non-diarrhea [88] ones, 83 (61.02%) C. perfringens were
cultured. Of these 83, 79 C. perfringens isolates showed the alpha-toxin
(phospholipase C) production gene by PCR. Respectively, 3 (9.09%) and 2 (4.34%)
cpe genes were present in diarrhea and non-diarrhea samples. Of 79 isolates of C.
perfringens, 34 (43.03%) cases showed no resistance, 18 (22.78%) had one
resistance and 27 (34.17%) isolates had multiple resistance to imipenem,
metronidazole, ceftriaxone, clindamycin, chloramphenicol, and penicillin.
CONCLUSIONS: Periodic evaluation of antimicrobial susceptibility for C.
perfringens should be performed. Harboring of enterotoxigenic C. perfringens in
individuals not necessarily results in diarrhea.
PMID- 26421136
TI - An Ultra-Violet Tolerant Wild-Type Strain of Melanin-Producing Bacillus
thuringiensis.
AB - BACKGROUND: Bacillus thuringiensis is the most successful biological control
agent used in agriculture, forestry and mosquito control. However, the
insecticidal activity of the B. thuringiensis formulation is not very stable and
rapidly loses its biological activity under field conditions, due to the
ultraviolet radiation in sunlight. Melanin is known to absorb radiation therefore
photo protection of B. thuringiensis based on melanin has been extensively
studied. OBJECTIVES: The aim of this study was to find a wild type strain of
naturally melanin-producing B. thuringiensis to avoid any mutation or
manipulation that can affect the Cry protein content. MATERIALS AND METHODS:
Bacillus thuringiensis strains were isolated from soils of different States of
Mexico and pigment extraction was followed by lowering the pH to 2 using 1N HCl.
Pigment was characterized by some chemical tests based on its solubility,
bleaching by H2O2 and flocculation with FeCl3, and using an Infrared (IR)
spectrum. Ultraviolet (UV) irradiation experiment was performed to probe the
melanin efficacy. RESULTS: ELI52 strain of B. thuringiensis was confirmed to
naturally produce melanin. The Cry protein analysis suggested that ELI52 is
probably a B. thuringiensis subsp. israelensis strain with toxic activity against
the Diptera order of insects. Ultra Violet protection efficacy of melanin was
probed counting total viable colonies after UV radiation and comparing the
results with the non-producing melanin strain L-DOPA (L-3, 4
dihydroxyphenylalanine) was also detected in the culture. ELI52 strain showed an
antagonistic effect over some common bacteria from the environment. CONCLUSIONS:
ELI52 wild-type strain of B. thuringiensis is a good bio-insecticide that
produces melanin with UV-resistance that is probably toxic against the Diptera
order of insects and can inhibit the growth of other environmental bacteria.
PMID- 26421137
TI - Prevalence and Clonal Dissemination of Metallo-Beta-Lactamase-Producing
Pseudomonas aeruginosa in Kermanshah.
AB - BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen associated with
nosocomial infections. The emergence and dissemination of metallo-beta-lactamases
(MBLs) has contributed to the high rate of resistance among P. aeruginosa
isolates. OBJECTIVES: The purpose of this study was to describe the prevalence
and the clonal dissemination of MBL- producing P. aeruginosa isolates collected
from major hospitals in Kermanshah. MATERIALS AND METHODS: Antibiotic
susceptibility testing was performed using the minimal inhibitory concentrations.
The MBLs were investigated using the Double-Disk Synergy Test (DDST) and
Polymerase Chain Reaction. Molecular typing was performed by Pulsed-Field Gel
Electrophoresis (PFGE). RESULTS: Of the 60 P. aeruginosa isolates included in
this study, 30 (50%) were resistant to Gentamicin, 38 (63.3%) to Piperacillin, 42
(70%) to Ceftazidime, and 45 (75%) to Cefepime. Twenty-nine (48.3%) isolates were
MBL producers in the DDST test. Five (8.3%) isolates were positive for the VIM
gene. PFGE analysis among the MBL producers revealed 12 distinct clonal patterns.
CONCLUSIONS: The inter- and intra-hospital dissemination of resistant clones is a
matter of concern and is an indicator of the level of the improvement and
surveillance of standard hygiene, particularly disinfection and hand washing
before and after contact with patients. Given the emergence of MBL-producing
strains, surveillance has become an important procedure to control the
transmission of resistant strains.
PMID- 26421138
TI - Analysis of Subcellular Prefoldin 1 Redistribution During Rabies Virus Infection.
AB - BACKGROUND: Rabies virus (RABV) is one of the old deadly zoonotic viruses. It
attacks the central nervous system and causes acute encephalitis in humans and
animals. Host factors are known to be essential for virus infection and
replication in cells. The identification of the key host factors required for
RABV infection may provide important information on RABV replication and may
provide new potential targets for RABV drug discovery. OBJECTIVES: This study
aimed to investigate the change in the subcellular distribution and expression of
the host protein Prefoldin subunit 1 (PFDN1) in RABV-infected cells and the viral
expression of plasmids in the transfected cells. MATERIALS AND METHODS: Mouse
Neuro-2a (N2a) cells were infected by RABV or transfected with the plasmids of
the nucleoprotein (N) and/or phosphoprotein (P) gene of RABV. The subcellular
distribution of PFDN1 was analyzed by confocal microscopy, and the transcription
levels of PFDN1 in the N and/or P gene of the RABV-transfected or RABV-infected
N2a cells were assessed via real-time quantitative polymerase chain reaction.
RESULTS: Confocal microscopy showed that PFDN1 was colocalized with the N protein
of RABV in the infected N2a cells and was mainly recruited to the characteristic
Negri-Body-Like (NBL) structures in the cytoplasm, as well as the cotransfection
of the N and P genes of RABV. The transcription of PFDN1 in the RABV-infected N2a
cells was upregulated, whereas the transfection of the N and/or P genes did not
result in the upregulation of PFDN1. CONCLUSIONS: The results of this work
demonstrated that the subcellular distribution of PFDN1 was altered in the RABV
infected N2a cells and colocalized with the N protein of RABV in the NBL
structures.
PMID- 26421139
TI - A Case of Recurrent Kikuchi-Fujimoto Disease.
AB - INTRODUCTION: Kikuchi-Fujimoto Disease (KFD) is a benign, self-limited,
inflammatory disorder, first reported in Japan. This condition is more prevalent
among women and typically occurs in the third decade of life. It normally
manifests as persistent, isolated cervical adenopathy with a recurrence rate of
3%. The identification of this condition is of high significance, given the risk
of misdiagnosis with other disorders such as malignant lymphoma and extensive
necrosis. CASE PRESENTATION: The patient was a 32-year-old female diagnosed with
Kikuchi-Fujimoto disease via neck lymph node biopsy in August 2006 in the city of
Mashhad, Iran. The disease regressed with proper follow-up, although after eight
years the patient was readmitted to the hospital with severe weight loss, high
fever, and uncommon symptoms of generalized adenopathy in cervical, axillary and
inguinal regions. CONCLUSIONS: Although KFD is an uncommon condition, it should
be featured in the list of differential diagnoses of tender lymphadenopathy,
especially lymphadenopathy localized to the cervical region. We reported a case
of KFD with a prolonged relapse of eight years. Full recovery with a good
response to corticosteroid regimen was achieved after the recurrence.
PMID- 26421140
TI - Molecular Identification of Resistance Determinants, Integrons and Genetic
Relatedness of Extensively Drug Resistant Acinetobacter baumannii Isolated From
Hospitals in Tehran, Iran.
AB - BACKGROUND: Acinetobacter baumannii has emerged as an important nosocomial
pathogen. Hospital outbreaks of extensively drug resistant (XDR) A. baumannii are
a great concern. OBJECTIVES: Aims of this study were to characterize the
resistance determinants and genetic relatedness of (XDR) A. baumannii isolates in
hospitals in Tehran, Iran. MATERIALS AND METHODS: During a three-year study,
clinical isolates of A. baumannii were collected from two hospitals in Tehran,
Iran. Susceptibility testing to antibiotics was performed by disk diffusion
method and XDR A. baumannii isolates were identified. Genes' encoding for
carbapenemase production and integrons were identified by PCR. MICs of imipenem
and meropenem were determined by agar dilution. Multiple locus variable-number
tandem repeat analysis (MLVA) typing was used to determine genetic relationships
of XDR isolates. RESULTS: Using PCR for amplification of bla OXA-51 , 93.9%
(123.131) of isolates were identified as A. baumannii and 24.4% (30.123) were
XDR. These isolates were resistant to gentamicin, ciprofloxacin, amikacin,
cotrimoxazole, cefepime, cefotaxime, aztreonam and ceftazidime. Thirty percent of
the isolates were resistant to tigecycline. All isolates were susceptible to
colistin and polymyxin-B, while 93.3% (28.30) possessed bla OXA-23 -like and 6.7%
(2.30) possessed bla OXA-24 -like. All isolates possessed insertion sequence
(ISAba1) in the upstream region of the OXA-23-like gene. Almost 96.7% (29.30) of
the isolates were positive for class I integron and 43.3% (13.30) for class II.
These isolates were also positive for class I. Class III integron was not
detected. MLVA typing of XDR isolates showed seven clonally complexes and 16
singletons. CONCLUSIONS: The population structure of the A. baumannii isolates in
our hospitals was genetically diverse. A significant association between XDR
pattern and presence of class 1 integron (P < 0.001) was found indicating that
many antibiotic resistance determinants are involved in development of XDR
strains.
PMID- 26421141
TI - Determination of the Genetic Diversity of Different Bioluminescent Bacteria by
Pulsed-Field Gel Electrophoresis (PFGE).
AB - BACKGROUND: There are 4 different genera (i.e. Vibrio, Aliivibrio,
Photobacterium, and Shewanella) in the new classification of bioluminescent
bacteria. The mechanism of bioluminescence has yet to be fully elucidated.
Therefore, the determination of physiological and genetic characteristics of
bioluminescent bacteria isolated from different sources is very important. Pulsed
Field Gel Electrophoresis (PFGE) has the highest discriminatory power among the
different molecular typing methods for the investigation of the clonal
relationships between bacteria. For the PFGE analysis of bioluminescent bacteria,
the NotI-HFTM is the method of choice among the restriction enzymes. OBJECTIVES:
The present study aimed to determine genetic relatedness via PFGE in 41
bioluminescent bacteria (belonging to 10 different species) isolated and
identified from various marine sources. MATERIALS AND METHODS: Different
bioluminescent bacteria (i.e. Vibrio gigantis, V. azureus, V. harveyi, V. lentus,
V. crassostreae, V. orientalis, Aliivibrio logei, A. fischeri, Shewanella woodyi,
and Photobacterium kishitanii) were analyzed by PFGE using the NotI-HFTM
restriction enzyme. The whole DNA of the strains embedded into the agarose plugs
was digested with enzyme at 37 degrees C for 30 minutes. CHEF-Mapper PFGE system
was used for electrophoresis and band profile of the strains for the NotI-HFTM
restriction enzyme were analyzed by Bio-Profil-1D++ software (Vilber Lourmat) at
10% homology coefficient. RESULTS: Although all experiments were performed three
times, four of forty-one bioluminescent strains (V. gigantis E-16, H-16 and S3W46
strains and A. fischeri E-4 strain) could not be typed by PFGE technique with
NotI-HFTM enzyme. While only two strains (V. crassostreae H-12 and H-19 strains)
were exhibiting same band pattern profiles (100% genome homology), thirty-six
different PFGE band patterns were obtained. Pattern homologies changed between
66% - 92%, 73% - 83% and 49% - 100% for V. gigantis, V. harveyi and other
strains, respectively. CONCLUSIONS: The obtained results revealed that there has
been a high rate of genetic diversity in bioluminescent strains isolated from
Gulf of Izmir and V. lentus and V. crassostreae strains could be also
bioluminescent for the first report. At the same time, PFGE analysis of
bioluminescent bacteria including four different genera and ten different species
were shown for the first time by this study. It is considered that data acquired
by this study will contribute evolution and mechanism of bioluminescence to
further works to be done.
PMID- 26421142
TI - Metformin as an anticancer drug: A Commentary on the metabolic determinants of
cancer cell sensitivity to glucose limitation and biguanides.
PMID- 26421143
TI - Epidermal growth factor receptor signaling and the progression of diabetic
nephropathy.
PMID- 26421145
TI - Highly reliable behaviors.
AB - A lack of respect between nursing and medical disciplines can lead to a lack of
trust and disruptive behaviors that are a significant part of the culture of
health care today. In order to ensure the best care for all patients, a
systematic approach to defining desired and undesired behaviors is a place to
begin. A systems view requires an appreciation of local culture and operations.
Understanding the underlying root causes in different departments and specialties
allows for the development and implementation of sustainable solutions which will
ultimately change and transform an organization. Leadership action and commitment
at the highest strategic level is essential for this to occur.
PMID- 26421144
TI - Comparative expression of the four enamel matrix protein genes, amelogenin,
ameloblastin, enamelin and amelotin during amelogenesis in the lizard Anolis
carolinensis.
AB - BACKGROUND: In a recent study, we have demonstrated that amelotin (AMTN) gene
structure and its expression during amelogenesis have changed during tetrapod
evolution. Indeed, this gene is expressed throughout enamel matrix deposition and
maturation in non-mammalian tetrapods, while in mammals its expression is
restricted to the transition and maturation stages of amelogenesis. Previous
studies of amelogenin (AMEL) gene expression in a lizard and a salamander have
shown similar expression pattern to that in mammals, but to our knowledge there
are no data regarding ameloblastin (AMBN) and enamelin (ENAM) expression in non
mammalian tetrapods. The present study aims to look at, and compare, the
structure and expression of four enamel matrix protein genes, AMEL, AMBN, ENAM
and AMTN during amelogenesis in the lizard Anolis carolinensis. RESULTS: We
provide the full-length cDNA sequence of A. carolinensis AMEL and AMBN, and show
for the first time the expression of ENAM and AMBN in a non-mammalian species.
During amelogenesis in A. carolinensis, AMEL, AMBN and ENAM expression in
ameloblasts is similar to that described in mammals. It is noteworthy that AMEL
and AMBN expression is also found in odontoblasts. CONCLUSIONS: Our findings
indicate that AMTN is the only enamel matrix protein gene that is differentially
expressed in ameloblasts between mammals and sauropsids. Changes in AMTN
structure and expression could be the key to explain the structural differences
between mammalian and reptilian enamel, i.e. prismatic versus non-prismatic.
PMID- 26421146
TI - High-coverage sequencing and annotated assembly of the genome of the Australian
dragon lizard Pogona vitticeps.
AB - BACKGROUND: The lizards of the family Agamidae are one of the most prominent
elements of the Australian reptile fauna. Here, we present a genomic resource
built on the basis of a wild-caught male ZZ central bearded dragon Pogona
vitticeps. FINDINGS: The genomic sequence for P. vitticeps, generated on the
Illumina HiSeq 2000 platform, comprised 317 Gbp (179X raw read depth) from 13
insert libraries ranging from 250 bp to 40 kbp. After filtering for low-quality
and duplicated reads, 146 Gbp of data (83X) was available for assembly.
Exceptionally high levels of heterozygosity (0.85 % of single nucleotide
polymorphisms plus sequence insertions or deletions) complicated assembly;
nevertheless, 96.4 % of reads mapped back to the assembled scaffolds, indicating
that the assembly included most of the sequenced genome. Length of the assembly
was 1.8 Gbp in 545,310 scaffolds (69,852 longer than 300 bp), the longest being
14.68 Mbp. N50 was 2.29 Mbp. Genes were annotated on the basis of de novo
prediction, similarity to the green anole Anolis carolinensis, Gallus gallus and
Homo sapiens proteins, and P. vitticeps transcriptome sequence assemblies, to
yield 19,406 protein-coding genes in the assembly, 63 % of which had intact open
reading frames. Our assembly captured 99 % (246 of 248) of core CEGMA genes, with
93 % (231) being complete. CONCLUSIONS: The quality of the P. vitticeps assembly
is comparable or superior to that of other published squamate genomes, and the
annotated P. vitticeps genome can be accessed through a genome browser available
at https://genomics.canberra.edu.au.
PMID- 26421147
TI - Tip of the iceberg: Extra-haematological consequences of early iron deficiency.
PMID- 26421148
TI - Osteogenic programs during zebrafish fin regeneration.
AB - Recent advances in genomic, screening and imaging technologies have provided new
opportunities to examine the molecular and cellular landscape underlying human
physiology and disease. In the context of skeletal research, technologies for
systems genetics, high-throughput screening and high-content imaging can aid an
unbiased approach when searching for new biological, pathological or therapeutic
pathways. However, these approaches necessitate the use of specialized model
systems that rapidly produce a phenotype, are easy to manipulate, and amenable to
optical study, all while representing mammalian bone physiologies at the
molecular and cellular levels. The emerging use of zebrafish (Danio rerio) for
modeling human disease highlights its potential to accelerate therapeutic and
pathway discovery in the mammalian skeleton. In this review, we consider the
potential value of zebrafish fin ray regeneration (a rapid, genetically tractable
and optically transparent model of intramembranous ossification) as a
translational model for such studies.
PMID- 26421149
TI - Preparation for teacher collaboration in inclusive classrooms - stress reduction
for special education students via acceptance and commitment training: A
controlled study.
AB - BACKGROUND: The education system in Germany is beginning to witness a sea change,
lately, owing to the country's ratification of the United Nation's Convention on
the Rights of Persons with Disabilities. The enactment is aiming at making
provision for special education teachers to share the same teaching platform and
institution with other teachers for teaching children from all backgrounds,
irrespective of their needs. While promoting the benefits of collaborative
teaching, this provision would also effectively establish role demarcation among
teachers. However, the level of participation and adaptiveness displayed by
individual teachers would play a major role in determining the success or failure
of the intended collaborative framework. Collaboration also becomes challenging
due to the level of stress involved in the teaching profession. The fact that
only 65 % of teachers in Germany reach retirement age while still in service,
primarily due to psychiatric illness, has posed questions on adopting the
collaborative framework for teachers from diverse backgrounds. In other words, it
can be stated that the process of collaborating with teachers from different
professional backgrounds and with varying levels of skills will potentially lead
to further stress. The stress-related psychological states, developed through the
collaborative processes, might affect the biological stress-response systems of
the participating teachers. With stress-response contributing directly to the
pathogenesis of stress-related diseases and disorders in the long term, it would
be important to contain the ripple effect of collaborative framework that the
enactment intends to establish between SEN (special educational needs) teachers
and others. METHODS: In addition to impacting the long-term health of teachers,
the collaborative framework is also suggestive of having similar effects on
students studying special education (SEN students). A study was conducted to
examine the stress levels associated with the collaborative framework. An
expression in terms of two (group affiliation) * 2 (measurement time) between
subjects design was implemented to examine the effects of an Acceptance and
Commitment Training on the subjective tension of a sample (N = 68) of SEN
students. The sample was split into an intervention and a control group (IG and
CG). The effects of the training on collaborative competence were examined using
the Chi-square test. Questionnaire and role plays were used to assess the
collaborative competence and the subjective tension. RESULTS: The participants
had significant stress levels and displayed an uncooperative attitude during the
initial assessment. However, these results reversed after the Acceptance and
Commitment Training. Significant decrease in stress levels and improved
cooperation were evident among the participants in the intervention group, as
opposed to the participants of the control group. CONCLUSIONS: The findings of
this study show that the Acceptance and Commitment Training is an appropriate
medium to establish and develop collaboration skills, and an effective technique
to reduce high levels of subjective stress. Furthermore, the training evaluation
and feedback indicate that it is well-accepted by all participants. The training
is also endorsed as a practically relevant medium to help SEN students
collaborate and combat stress.
PMID- 26421150
TI - The metabolomics of asthma control: a promising link between genetics and
disease.
AB - Short-acting beta agonists (e.g., albuterol) are the most commonly used
medications for asthma, a disease that affects over 300 million people in the
world. Metabolomic profiling of asthmatics taking beta agonists presents a new
and promising resource for identifying the molecular determinants of asthma
control. The objective is to identify novel genetic and biochemical predictors of
asthma control using an integrative "omics" approach. We generated lipidomic data
by liquid chromatography tandem mass spectrometry (LC-MS), - using plasma samples
from 20 individuals with asthma. The outcome of interest was a binary indicator
of asthma control defined by the use of albuterol inhalers in the preceding week.
We integrated metabolomic data with genome-wide genotype, gene expression, and
methylation data of this cohort to identify genomic and molecular indicators of
asthma control. A Conditional Gaussian Bayesian Network (CGBN) was generated
using the strongest predictors from each of these analyses. Integrative and
metabolic pathway over-representation analyses (ORA) identified enrichment of
known biological pathways within the strongest molecular determinants. Of the 64
metabolites measured, 32 had known identities. The CGBN model based on four SNPs
(rs9522789, rs7147228, rs2701423, rs759582) and two metabolites-monoHETE_0863 and
sphingosine-1-phosphate (S1P) could predict asthma control with an AUC of 95%.
Integrative ORA identified 17 significantly enriched pathways related to cellular
immune response, interferon signaling, and cytokine-related signaling, for which
arachidonic acid, PGE2 and S1P, in addition to six genes (CHN1, PRKCE, GNA12,
OASL, OAS1, and IFIT3) appeared to drive the pathway results. Of these
predictors, S1P, GNA12, and PRKCE were enriched in the results from integrative
and metabolic ORAs. Through an integrative analysis of metabolomic, genomic, and
methylation data from a small cohort of asthmatics, we implicate altered
metabolic pathways, related to sphingolipid metabolism, in asthma control. These
results provide insight into the pathophysiology of asthma control.
PMID- 26421151
TI - Reproductive constraints influence habitat accessibility, segregation, and
preference of sympatric albatross species.
AB - BACKGROUND: The spatiotemporal distribution of animals is dependent on a suite of
factors, including the distribution of resources, interactions within and between
species, physiological limitations, and requirements for reproduction, dispersal,
or migration. During breeding, reproductive constraints play a major role in the
distribution and behavior of central place foragers, such as pelagic seabirds. We
examined the foraging behavior and marine habitat selection of Laysan
(Phoebastria immutabilis) and black-footed (P. nigripes) albatrosses throughout
their eight month breeding cycle at Tern Island, Northwest Hawaiian Islands to
evaluate how variable constraints of breeding influenced habitat availability and
foraging decisions. We used satellite tracking and light-based geolocation to
determine foraging locations of individuals, and applied a biologically realistic
null usage model to generate control locations and model habitat preference under
a case-control design. Remotely sensed oceanographic data were used to
characterize albatross habitats in the North Pacific. RESULTS: Individuals of
both species ranged significantly farther and for longer durations during
incubation and chick-rearing compared to the brooding period. Interspecific
segregation of core foraging areas was observed during incubation and chick
rearing, but not during brooding. At-sea activity patterns were most similar
between species during brooding; neither species altered foraging effort to
compensate for presumed low prey availability and high energy demands during this
stage. Habitat selection during long-ranging movements was most strongly
associated with sea surface temperature for both species, with a preference for
cooler ocean temperatures compared to overall availability. During brooding,
lower explanatory power of habitat models was likely related to the narrow range
of ocean temperatures available for selection. CONCLUSIONS: Laysan and black
footed albatrosses differ from other albatross species in that they breed in an
oligotrophic marine environment. During incubation and chick-rearing, they travel
to cooler, more productive waters, but are restricted to the low-productivity
environment near the colony during brooding, when energy requirements are
greatest. Compared to other albatross species, Laysan and black-footed
albatrosses spend a greater proportion of time in flight when foraging,
especially during the brooding period; this strategy may be adaptive for locating
dispersed prey in an oligotrophic environment.
PMID- 26421152
TI - Investigation of potential genotoxic activity using the SOS Chromotest for real
paracetamol wastewater and the wastewater treated by the Fenton process.
AB - BACKGROUND: The potential genotoxic activity associated with high strength real
paracetamol (PCT) wastewater (COD = 40,000 mg/L, TOC = 12,000 mg/L, BOD5 = 19,320
mg/L) from a large-scale drug-producing plant in the Marmara Region, was
investigated in pre- and post- treated wastewater by the Fenton process (COD =
2,920 mg/L, TOC = 880 mg/L; BOD5 = 870 mg/L). METHODS: The SOS Chromotest, which
is based on Escherichia coli PQ37 activities, was used for the assessment of
genotoxicity. The corrected induction factors (CIF) values used as quantitative
measurements of the genotoxic activity were obtained from a total of four
different dilutions (100, 50, 6.25, and 0.078 % v/v.) for two samples, in
triplicate, to detect potentially genotoxic activities with the SOS Chromotest.
RESULTS: The results of the SOS Chromotest demonstrated CIFmax value of 1.24,
indicating that the PCT effluent (non-treated) is genotoxic. The results of the
SOS Chromotest showed an CIFmax value of 1.72, indicating that the wastewater
treated by Fenton process is genotoxic. CONCLUSIONS: The findings of this study
clearly reveal that the PCT wastewater (non-treated) samples have a potentially
hazardous impact on the aquatic environment before treatment, and in the
wastewater that was treated by the Fenton process, genotoxicity generally
increased.
PMID- 26421153
TI - A survey on parasite management by equine veterinarians highlights the need for a
regulation change.
AB - INTRODUCTION: In-depth knowledge of the use of anthelminthics in the field,
especially by veterinarians, is required to design more sustainable parasite
control strategies. MATERIALS AND METHODS: An online survey was sent by e-mail to
940 equine veterinary practitioners to describe their equine practice, their
awareness about parasites and the management strategies they apply. RESULTS:
Gastrointestinal parasites were generally considered (68%) as an issue of
moderate importance. Drug efficacy failure was a minor or moderate issue for 47%
and 48% of responders, respectively. Parasite management mostly relied on the use
of systematic calendar treatments across a wide variety of horse owners (ie,
riding schools, studs or hobby horse owners). Almost half of the practitioners
(42%) never performed Faecal Egg Count (FEC) before drenching. Horse owners or
their employees in charge of equines were reported to be the only person managing
drenching in 59% of the collected answers. This was associated with the report of
many off-label uses of anthelmintics and the frequent buying of drugs using the
internet. CONCLUSIONS: Given the critical situation regarding anthelmintic
resistance, it seems necessary for veterinarians to reclaim parasite management
and prevention as a specific topic. Implementation of stricter regulations for
use of anthelmintics, like the one applied in Denmark, may make parasitic
management in equids more sustainable.
PMID- 26421154
TI - Cardiac device-associated lead infection: a diagnosis not to be missed.
AB - A 66-year-old gentleman was admitted to hospital with a history of general
malaise for 5 months. His symptoms worsened 2 weeks prior to presentation. He
experienced swinging pyrexia, night sweats and shortness of breath on exertion.
Initial evaluation did not reveal any source of infection. Subsequent
investigation revealed infection with vegetation affecting the intra-cardiac
leads of cardiac resynchronization therapy device (CRT-D). The patient was
treated with prolonged intravenous antibiotics and removal of the device and
indwelling leads. The patient made a full recovery and a new device was
implanted.
PMID- 26421155
TI - Allergic angina following wasp sting: Kounis syndrome.
AB - Kounis syndrome is defined as an acute coronary syndrome triggered by the release
of inflammatory mediators following an allergic insult characterized by acute
onset of breathlessness, palpitations, diaphoresis and chest tightness (Gazquez
V, Dalmau G, Gaig P, Gomez C, Navarro S, Merce J. Kounis syndrome: report of 5
cases. J Investig Allergol Clin Immunol 2010;20:162-5). We report a 20-year-male
patient who presented with acute myocardial infarction following a wasp sting at
our institute. ECG showed non-ST-elevation myocardial infarction. Symptoms
settled with hydrocortisone and adrenaline. Coronary angiogram revealed normal
epicardial coronaries.
PMID- 26421156
TI - Acute renal vein thrombosis and nephrotic syndrome in the setting of
retroperitoneal fibrosis.
AB - Idiopathic retroperitoneal fibrosis (RPF) is a rare disease that involves non
specific inflammation and fibrosis surrounding the aorta. As a result, RPF is a
challenging diagnosis to make; patients often seek medical attention after
complications arise, such as nephrotic syndrome. The patient in our case report
initially complained of flank pain. Laboratory evaluation revealed acute renal
failure and nephrotic syndrome with substantial proteinuria. Multiple imaging
modalities demonstrated a large, ill-defined, infiltrative retroperitoneal soft
tissue mass that encased the great vessels. The patient was also noted to have
acute left renal vein thrombosis. Although the patient was eventually diagnosed
with RPF of unknown etiology, his clinical course is particularly unique given
the rarity of the renal vein thrombosis. This case report adds a value to the
medical community by helping to elucidate RPF and exposing its potentially life
threatening complications.
PMID- 26421157
TI - Neuro-Behcet's: a diagnostic challenge.
AB - Behcet's disease (BD) is characterized by recurrent oral and genital ulcers and
uveitis. It is also known to affect various organs; however, central nervous
system involvement is rare and may cause parenchymal or vascular lesions with
distinct clinical syndromes. Various viral encephalitides are important
differential diagnoses. MRI may aid the correct diagnosis. This case report
describes a patient with acute severe neurological involvement due to neuro-BD.
PMID- 26421158
TI - Spontaneous oesophageal rupture: a diagnostic challenge in resource-limited
setting.
AB - Spontaneous oesophageal rupture after swallowing a bolus of food is a very rare
condition. In resource-limited settings, it is very challenging to diagnose this
condition especially when its presentation is atypical. Its prognosis is very
poor when diagnosis is delayed due to risk of mediastinitis. We report a case of
37-year-old man who was admitted to our hospital complaining of sudden onset of
chest tightness and pain after a meal 8 h prior to admission. Urgent chest
radiograph revealed right hydropneumothorax with collapsed lung. Water-seal
drainage was established gushing 1200 ml of food materials. Definitive diagnosis
of oesophageal rupture was reached after post-mortem.
PMID- 26421159
TI - Complete stent fracture 1 year after LIMA PCI due to LIMA and subclavian artery
dissection.
AB - Stent platforms are prone to fracture while incidental data are demonstrating a
potential unfavorable outcome. Predisposing factors usually involve long lesions
and tortuous vessels requiring more than one stent. This issue is magnified when
it involves a periprocedural iatrogenic left internal mammary artery (LIMA) and
subclavian artery dissection. In such complex clinical scenarios, the risk of
potential complications including stent fractures is thought to be higher, though
there is no data to determine the prognosis or to outline the outcomes of any
management option. We present a case of complete stent fracture 1 year after LIMA
percutaneous coronary intervention due to LIMA and subclavian artery dissection
highlighting the circumstantial evidence in the literature that guided our
management decisions.
PMID- 26421160
TI - Corticosteroid induced hyperosmolar hyperglycaemic state and hemiballismus.
AB - We present an 89-year-old man with new onset of left-sided hemiballismus
affecting his face, arm and leg. He was found to have hyperglycaemia with a
glucose level of 20.2 mmol/l and had started prednisolone 3 months earlier for
polymyalgia rheumatica. A T 2-weighted magnetic resonance scan of the brain
showed a hypointense lesion of the right lentiform nucleus. At follow-up, his
symptoms had improved with treatment for diabetes mellitus. To our knowledge,
this is the first patient to develop hemiballismus after starting
corticosteroids.
PMID- 26421161
TI - An unusual cause of suicidal ideations.
AB - While the differential for suicidal ideations is broad, it is known that
pathologic brain issues are a cause. Here, a case is presented of a gentleman who
had an unusual growth into his frontal lobe leading to the suicidal ideations.
The fact that he is chronically immunosuppressed likely led to this unique
situation.
PMID- 26421162
TI - Diseases Led to Refer Iranian Pilgrims From Hajj in 2012.
AB - BACKGROUND: Some Iranian pilgrims are referred to Iran because of catching a new
disease or exacerbation of their disease during the Hajj ceremony. These diseases
need prolonged and specialized treatments. Investigation of the reasons led to
their return to Iran is useful and effective in policy-making and planning of
preventive health services. OBJECTIVES: This study aimed to investigate the
causes of referring Iranian patients to Iran during Hajj in 2010. PATIENTS AND
METHODS: In this cross-sectional study, all Iranian pilgrim cases in Hajj (2012)
who referred to Iran were studied, and data analysis was performed. Demographic
data and the causes of return to Iran during and after Hajj rituals were
analyzed. RESULTS: A total of 106 cases were referred Iran during Hajj 2012.
Psychiatric problems, with 26.4% allocated the highest rate of return to Iran
during Hajj days, and significant difference was observed in the reasons before
and after performing Hajj rituals (P = 0.001). CONCLUSIONS: Psychiatric,
neurological, gastrointestinal, and respiratory diseases are the most frequent
reasons of referring patients to Iran. More accuracy in screening and care of
patients are recommended before Hajj in order to prevent references to Iran and
its complications.
PMID- 26421163
TI - Impact of Oral Sensory Motor Stimulation on Feeding Performance, Length of
Hospital Stay, and Weight Gain of Preterm Infants in NICU.
AB - BACKGROUND: One of the limiting factors for early hospital discharge in preterm
infants is their inability to feed sufficiently to obtain consistent weight gain.
Therefore, feeding difficulty is one of the most significant issues with which a
preterm infant is faced. OBJECTIVES: The purpose of this study was to examine the
effect of oral sensory motor stimulation on feeding performance, length of
hospital stay, and weight gain in preterm infants at 30 - 32 weeks of gestational
age. PATIENTS AND METHODS: Premature infants (n = 20) were randomly assigned to
experimental and control groups. The experimental group received oral sensory
motor stimulation of the oral structures (15 minutes / day) for 10 successive
days, while these stimulations were not offered to the control group. Days
elapsed to achieve oral feeding, length of hospital stay, and weight gain in the
two groups were assessed. RESULTS: Transition to oral feeding was acquired
significantly earlier in the infants in the experimental group than in the
controls: 13 and 26 days, respectively (P < 0.001). Likewise, the length of
hospitalization was significantly shorter in the experimental group than in the
control group: 32 days and 38 days, correspondingly (P < 0.05). The two groups
showed no significant difference in terms of weight gain in the first, second,
third, and fourth weeks of birth: first week: 100 vs. 110; second week: 99 vs.
111; third week: 120 vs. 135; and fourth week: 129 vs. 140. CONCLUSIONS: The
present research revealed that the number of days to reach oral feeding in our
preterm babies was decreased by oral motor stimulation, which in turn conferred
earlier hospital discharge.
PMID- 26421164
TI - Epidemiology and Management Cost of Myocardial Infarction in North Punjab,
Pakistan.
AB - BACKGROUND: Coronary heart disease (CHD) is an important cause of morbidity and
mortality in Pakistan. The temporal trends in the risk factors for myocardial
infarction (MI) and the impact of socioeconomic status on these risk factors
remain ambiguous. OBJECTIVES: The objectives of the present analysis were to
investigate the potential association between various risk factors and MI in
North Punjab, Pakistan, and to assess the status of the control of the risk
factors associated with MI in this population. PATIENTS AND METHODS: The present
study included 515 patients admitted to the coronary care units or equivalent
cardiology wards of the participating hospitals between 2011 and 2012 in North
Punjab, Pakistan. The analysis was focused on identifying the socioeconomic
status, lifestyle, family history of MI, and risk factors (i.e. hypertension,
diabetes, smoking, and hyperlipidemia). A structured questionnaire was designed
to collect data. The lipid profile was recorded from the investigation chart of
every patient. For statistical analysis, the Kruskal Wallis, Mann-Whitney U,
Wilcoxon, and chi-square tests were used. RESULTS: MI was common in the males at
the age of 41 - 60 years as compared to the females (P = 0.015). Patients with a
positive parental history of CHD experienced MI at a younger age (P = 0.0001) at
a body mass index (BMI) <= 25 kg/m(2). Sedentary lifestyle (70%) and smoking
(60%) had a male predominance. Hypertension accounted for nearly 37%,
hyperlipidemia 26%, and diabetes 19.4% of the rural and urban subjects (P <
0.01). High-density lipoprotein cholesterol decreased (up to 34 mg/dl), while low
density lipoprotein cholesterol and hypertension increased with age. The mean
monthly cost of medicines and physicians' fees per patient was 2381.132 Pakistani
Rupees (24.24 USD). CONCLUSIONS: Higher BMI, positive family history, smoking,
hypertension, hyperlipidemia, and diabetes were the strong predictors of MI in
North Punjab, Pakistan. Preventive efforts are needed to start early in life and
continue throughout the life course.
PMID- 26421165
TI - Traumatic Lumbosacral Spondylolisthesis: A Case Report.
AB - INTRODUCTION: Traumatic lumbar spondylolisthesis is rare disease and in the
literature, different surgical approaches, including anterior, posterior, or
combined approaches (posterior and anterior) are used to treat the lesion. CASE
PRESENTATION: We treated a case of traumatic lumbosacral spondylolisthesis using
posterior approach and the patient showed a satisfactory outcome. At the final
follow-up, he was completely asymptomatic, and radiographic images revealed
normal lumbar alignment and a solid interbody fusion. CONCLUSIONS: Traumatic
lumbosacral spondylolisthesis can be treated using posterior approach alone to
obtain reduction, decompression, and solid fusion.
PMID- 26421166
TI - Desmopressin, Imipramine, and Oxybutynin in the Treatment of Primary Nocturnal
Enuresis: A Randomized Clinical Trial.
AB - BACKGROUND: Nocturnal enuresis is the most common pediatric urologic problem in
outpatient clinics. OBJECTIVES: To assess the effect of various monotherapies,
and comparing the effects of desmopressin, imipramine, and oxybutynin in children
with enuresis, as well as the influence of socioeconomic and cultural factors of
their families on the response and relapse rates. PATIENTS AND METHODS: The study
was a randomized clinical trial conducted on 92 children aged 5 - 14 years,
referred to the pediatric clinic of Semnan University Hospital in Semnan, Iran.
Children with primary nocturnal enuresis were randomly allocated to three
different treatment groups: desmopressin (n = 30), imipramine (n = 31), and
oxybutynin (n = 31) all for 6 weeks. The socioeconomic and demographic
characteristics of all participants were recorded. The number of wet nights per
week was noted at the end of the 6-week-trial, and children were followed up to
three months for relapse. RESULTS: Children in the oxybutynin group showed a
slightly higher response rate (71.0% success) and a lower relapse rate (31.8%),
while in the desmopressin group the response and relapse rates were 63.3% and
57.9%, respectively, and in the imipramine group 61.3% and 63.2%, respectively.
However, the difference between the 3 groups in terms of response (P = 0.701) and
relapse rates (P = 0.095) was not statistically significant. CONCLUSIONS: There
is no significant difference between monotherapy with desmopressin, imipramine or
oxybutynin in children with enuresis. However, oxybutynin showed a higher
response rate and a lower relapse rate compared to other medications. More
clinical trials with a larger sample size are needed to clarify these
uncertainties.
PMID- 26421167
TI - Clinical Assessment of Nursing Care Regarding Hemovigilance in Neonatal Wards and
Neonatal Intensive Care Units in Selected Hospitals Affiliated to Shahid Beheshti
University of Medical Sciences (2013 - 2014).
AB - BACKGROUND: Hemovigilance is a series of surveillance procedures encompassing the
entire transfusion chain from the collection of blood and its components to the
follow-up of its recipients. It is intended to collect and access information on
unanticipated or adverse effects stemming from the therapeutic use of labile
blood products. Blood transfusion, particularly in neonates, requires meticulous
clinical assessment to ensure safety before, during, and after the procedure.
Therefore, it is essential to investigate how nurses and other health care
providers implement hemovigilance with a view to elevating the standards of care.
OBJECTIVES: The aim of this study, conducted between 2013 and 2014, was to assess
nursing care regarding hemovigilance in the neonatal wards and neonatal intensive
care units (NICUs) of selected hospitals affiliated to Shahid Beheshti University
of Medical Sciences. MATERIALS AND METHODS: This descriptive study assessed
nursing care concerning hemovigilance in 144 neonates. Data were collected using
a checklist at the neonatal wards and NICUs of Mahdiyeh, Mofid, and Imam Hussain
hospitals affiliated to Shahid Beheshti University of Medical Sciences. The
checklist contained information on the standard of care in relation to neonatal
hemovigilance in three components of request, transfusion, and documentation.
Descriptive statistics with the Statistical Package for the Social Sciences
(version 21) were used to analyze the collected data. RESULTS: The rates of
compliance with the hemovigilance guidelines in terms of request, transfusion,
and documentation were 47%, 63.2%, and 68%, correspondingly, with a total score
of 59.6% in all areas of research. Accordingly, compliance with hemovigilance
guidelines was highest in documentation (68%), followed by transfusion (63.2%)
and request (47%). CONCLUSIONS: The overall score of nursing care as regards
adherence to the neonatal hemovigilance guidelines was 59.6% in the present
study, indicating a lack of care and failure in training in this regard.
PMID- 26421168
TI - Prevalence of Hepatitis B Surface Antigen in Pregnant Women in Beheshti Hospital
of Kashan, Isfahan.
AB - BACKGROUND: The transmission of hepatitis B virus (HBV) is parenteral, sexual and
prenatal. Prevention of vertical transmission of HBV is extremely important,
because HBV infection in early life usually results in a chronic carrier state.
There has been so much debate about hepatitis B surface antigen (HBsAg) screening
in pregnant women. OBJECTIVES: The aim of this study was to determine the
prevalence of HBsAg+ among pregnant women referred to Beheshti hospital in Kashan
in 2012. PATIENTS AND METHODS: This descriptive study was carried out on 768
pregnant women, hospitalized in Beheshti Hospital of Kashan in 2012. After
obtaining consent forms, the questionnaires including demographic and HBV
infection-associated risk factors were filled through interview and then 5 mL
blood was taken from each patient and HBsAg was examined by the enzyme-linked
immunosorbent assay (ELISA) method. These data were analyzed by statistical
package for the social science (SPSS) software. RESULTS: A total of 12 (1.56%)
out of 768 pregnant women were HBsAg+. The mean age of HBsAg+ cases was 24.5 +/-
4 years. Most of the HBsAg+ cases (66.6%) were uneducated; 17.7% of the pregnant
women were not Iranian, of which 7.4% were HBsAg+. There was no high-risk job,
recent dentistry interruption or skin tattoo among the HBsAg+ cases. CONCLUSIONS:
In this study, 1.56% of pregnant women were HBsAg+, which was higher than the
previous studies. This increasing prevalence may be due to the increase of non
Iranians' migrations to Iran. Control of migration and screening and vaccination
of these groups should be considered by health policy makers.
PMID- 26421169
TI - Study of Psycho-Social Factors Affecting Traffic Accidents Among Young Boys in
Tehran.
AB - BACKGROUND: Unprecedented growth of fatalities due to traffic accidents in the
recent years has raised great concerns and efforts of authorities in order to
identify and control the causes of these accidents. OBJECTIVES: In the present
study, the contribution of psychological, social, demographic, environmental and
behavioral factors on traffic accidents was studied for young boys in Tehran,
emphasizing the importance of psychosocial factors. PATIENTS AND METHODS: The
design of the present study was quantitative (correlational) in which a sample
population including 253 boys from Tehran (Iran) with an age range of 18 to 24
who had been referred to insurance institutions, hospitals, correctional
facilities as well as prisons, were selected using stratified cluster sampling
during the year 2013.The subjects completed the following questionnaires:
demographic, general health, lifestyle, Manchester Driving Behavior Questionnaire
(MDBQ), young parenting, and NEO-Five Factor Inventory (NEO-FFI). For data
analysis, descriptive statistics, correlation coefficient, and inferential
statistics including simultaneous regression, stepwise regression, and structural
equations modeling were used. RESULTS: The findings indicated that in the
psychosocial model of driving behavior (including lapses, mistakes, and
intentional violations) and accidents, psychological factors, depression (P <
0.02), personality trait of conscientiousness (P < 0.02), failure schema due to
the parenting style of mother (P = 0.001), and perception of police commands (P <
0.002), played an important role in predicting driving behavior. Among social
factors, perception of police regulations (P = 0.003), had an important effect on
violations and mistakes. Among environmental and behavioral factors, major
factors such as driving age (P = 0.001), drug and alcohol use (P = 0.001), having
driver's license (P = 0.013), records of imprisonment or committing a crime (P =
0.012) were also able to predict occurrence of accidents. CONCLUSIONS: As the
results of this study show, different factors contribute to different driving
behaviors and accidents. The broad scope of these factors links accidents to
other social issues and damages.
PMID- 26421170
TI - Prognostic Significance of Nuclear beta-Catenin Expression in Patients with
Colorectal Cancer from Iran.
AB - BACKGROUND: Beta catenin plays a key role in cancer tumorigenesis. However, its
prognostic significance in patients with colorectal cancer (CRC) remains
controversial. It has been demonstrated that 90% of all tumors have a mutation in
individual components of multiple oncogenes in Wnt/beta-catenin pathway.
Accumulation of nuclear beta-catenin in cytoplasm leads to uncontrolled cell
proliferation. Thus, nuclear beta-catenin accumulation may be a valuable
biomarker associated with invasion, metastasis and poor prognosis of CRC.
OBJECTIVES: In this study the prognostic value of beta catenin expression in 165
Iranian CRC patients was evaluated. PATIENTS AND METHODS: In this cross sectional
retrospective study immunohistochemistry analyses of formalin-fixed paraffin
embedded (FFPE) tumor tissues were performed to characterize the expression of
nuclear beta-catenin in a series of 165 Iranian patients with colorectal
carcinoma. Heat-induced antigen retrieval using the microwave method was applied
for all staining procedures. Staining was scored independently by two observers,
and a high level of concordance (90%) was achieved. Statistical analysis was done
using the SPSS software for Windows, version 13.0.0 (SPSS Inc., Chicago, IL). Two
tailed P < 0.05 was considered statistically significant. RESULTS: The patients
consisted of 85 males and 80 females. Eighty-eight patients had primary tumor of
the rectum and sigmoid, while 77 patients had primary tumor of the colon. The
mean period of follow-up was 47.2 +/- 10 months and the median period of follow
up was 38 months (range 6 - 58) for each patient. Of 165 tumors, 32 tumors (19.39
%) showed expression of beta-catenin and 133 (80.6 %) were negative for beta
catenin expression. Based on our findings the distribution of Microsatellite
Instability (MSI) status differed between patients with nuclear beta-catenin
positive and negative tumors and this difference was significant (P = 0.001).
Patients with nuclear beta-catenin positive expression profile were found to be
younger than patients with negative nuclear beta-catenin expression (P = 0.010).
Univariate and multivariate analysis showed that tumors with beta-catenin
expression had a poorer prognosis compared to tumors without beta-catenin
expression. CONCLUSIONS: According to our findings, the distribution of nuclear b
catenin expression is a poor prognostic marker in patients with colon cancer.
PMID- 26421171
TI - Factors Influencing the Successful Aging of Iranian Old Adult Women.
AB - BACKGROUND: Aging is an irreversible natural process characterized by a decline
in both the physical and mental status of individuals. Because of multiple
factors, this process and its consequences vary greatly between individuals. A
successful aging (SA) is the target of current health policies and well-being of
individuals. Knowing the factors that contribute to SA and its barriers would
translate in measurements that increase the quality of life of elderly and reduce
health costs. OBJECTIVES: The aim of this study was to explore barriers and
facilitators to Iranian elderly women's SA. PATIENTS AND METHODS: A purposive
sample of 16 elderly women, aged 61 - 96 years, was recruited for this
qualitative content analysis study. Study data were collected during 2012 -.2013
by conducting 16 face-to-face semi-structured in-depth interviews. We continued
the data collection until reaching saturation. Study data were analyzed
concurrently with data collection, by using the conventional qualitative content
analysis approach. RESULTS: Barriers and facilitators to Iranian elderly women's
SA fell into five main categories, including availability of support systems,
state of health, personal capabilities, personality characteristics, and
lifestyle. CONCLUSIONS: Availability of support systems, state of health,
personal capabilities, personality characteristics, and lifestyle were the main
interrelated factors affecting Iranian elderly women's SA. Accordingly, providing
elderly women with strong educational, emotional, financial, cultural, and social
supports can help facilitate their SA.
PMID- 26421172
TI - Resiliency Improvements in Medical Emergency Staff in Burn Missions: A
Qualitative Study in an Iranian Context.
AB - BACKGROUND: Medical emergency staff complete understanding of the nature of
resiliency in burn events is a prerequisite for improving the quality of clinical
service delivery in pre-hospital burn events. OBJECTIVES: The present study aimed
to describe resiliency in view of medical emergency staff in burn events.
MATERIALS AND METHODS: The present qualitative study was performed using a
content analysis method. In total, 18 Iranian emergency care personnel
participated in the study. A purposeful sampling method was applied until
reaching data saturation. Data was collected using semi-structured interviews and
field observations. Afterwards, data was analyzed by face content analysis.
RESULTS: By analyzing 456 primary codes, four main concepts including: 1) scene
safety/security, 2) effective clinical decision making, 3) self-efficacy and 4)
religious support were extracted through content analysis from experiences of pre
hospital emergency personnel during burn care. CONCLUSIONS: Different factors
affect resiliency improvements in medical emergency staff and consequently the
quality of pre-hospital burn care. This study showed that various factors such as
scene security/safety, effective decision making, self-efficacy and religious
support are effective in the improvement of resiliency and the quality of pre
hospital emergency care.
PMID- 26421173
TI - Caloric Restriction and Formalin-Induced Inflammation: An Experimental Study in
Rat Model.
AB - BACKGROUND: Acute and chronic inflammations are difficult to control. Using
chemical anti-inflammatory medications along with their complications
considerably limit their use. According to Traditional Iranian Medicine (TIM),
there is an important relation between inflammation and Imtila (food and blood
accumulation in the body); food reduction or its more modern equivalent Caloric
Restriction (CR) may act against both Imtila and inflammation. OBJECTIVES: This
experimental study aimed to investigate the effect of 30% reduction in daily
calorie intake on inflammation in rats. MATERIALS AND METHODS: A total of 18 male
rats (Rattus rattus) weighing 220 to 270 g were obtained. Then, the inflammation
was induced by injecting formalin in their paws. Next, the rats were randomized
by generating random numbers into two equal groups (9 + 9) putting on either
normal diet (controls) or a similar diet with 30% reduction of calorie (cases).
Paw volume changes were recorded twice per day by one observer in both groups
using a standard plethysmometer for 8 consecutive days. Serum C-reactive protein
(CRP), Erythrocyte Sedimentation Rate (ESR), complete blood count (erythrocyte,
platelet, and white blood cell) and hemoglobin were compared between the groups.
RESULTS: Decline of both body weight and paw volume was significantly more
prominent in the case than in the control rats within the study period (P < 0.001
and < 0.001, respectively). Paw volume decrease was more prominent after day 3.
On day 8, serum CRP-positive (1 or 2 +) rats were more frequent in ad libitum fed
group comparing with those received CR (33.3% vs. 11.1%). This difference,
however, was insignificant (P = 0.58). At the same time, mean ESR was
significantly higher in the control rats comparing with that in the case group
(29.00 +/- 2.89 h vs. 14.00 +/- 1.55 h; P = 0.001). Other serum parameters were
not significantly different between the two groups at endpoint. CONCLUSIONS: Rats
fed with a 30% calorie-restricted diet in comparison with to ad libitum fed
controls for 8 days had significantly more prominent regression of inflammation.
PMID- 26421174
TI - A Semi-Experimental Study to Assess Whether the Current Recommended Protocol for
Treating Vitamin D Deficiency is Enough?
AB - BACKGROUND: Urbanization and diet change have increased the prevalence of Vitamin
D deficiency. Unfortunately, none of the suggested treatments is widely accepted.
OBJECTIVES: Therefore, we evaluated the most used and suggested protocol for
treating Vitamin D deficiency in Percutaneous coronary intervention (PCI)
candidate patients referred to our hospital in a short-term clinical trial.
PATIENTS AND METHODS: All patients with coronary artery disease, referred to our
hospital and candidates for PCI (drug eluted stents) were included. Deficient
patients were randomly assigned to treatment (Vitamin D3 pearls of 50,000 IU; one
per week for 10 weeks then one pearl every month for maintenance) and non
treatment groups. Vitamin D was measured after nine months. RESULTS: After
initial evaluation, 116 cases were found to be deficient, and were divided into
two equal groups of 58. No significant difference was found between the normal,
treated and non-treated groups regarding age and gender. Thirty-two out of 58
(55.1%) subjects were vitamin D deficient and reached normal levels by taking
supplements and seven out of 58 (12%) were deficient and reached normal levels
without taking supplements, with the difference being significant (P < 0.001).
CONCLUSIONS: The used protocol is not enough for treating Vitamin D deficiency.
Furthermore, the protocol should be revised according to baseline Vitamin D
classification.
PMID- 26421175
TI - No Evidence for Association Between Norepinephrine Transporter-3081 (A/T)
Polymorphism and Attention Deficit Hyperactivity Disorder in Iranian Population.
AB - BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) can lead to drastic
problems for the patient and its worldwide prevalence is 5%-12%. It also has many
comorbidities with other disorders, and the genetic contribution seems the most
significant cause. OBJECTIVES: The current study was conducted to investigate the
association between norepinephrine transporter-3081 (A/T) polymorphisms and ADHD
in Iranian population. PATIENTS AND METHODS: Participants were chosen from
children and adolescents diagnosed with ADHD referred to Imam Hoseyn Hospital. A
child and adolescent psychiatrist confirmed the diagnosis using the Kiddie-Sads
Present and Lifetime Version (K-SADS-PL) semi-structural interview. The control
group was from pupils of schools in Tehran (capital city of Iran) who had no
history or presence of psychiatric and medical complications. Also, a child and
adolescent psychiatrist confirmed their health using the K-SADS-PL semi
structural interview. Genetic examinations were DNA distraction, Polymerase Chain
Reaction (PCR), and Restricted Fragment Length Polymorphism (RFLP), which were
conducted according to standard protocols. The statistical analysis was performed
using chi-square and Fisher's exact test in SPSS version 21. RESULTS: The
percentages of ADHD subtypes for combined, inattentive, and hyperactive/impulsive
were 72.2%, 17.2%, and 11.9%, respectively. There was no significant association
between norepinephrine transporter polymorphism and ADHD (P = 0.81). Moreover, no
significant relationship was found between gender [male (P = 0.92) and female (P
= 0.63)] and polymorphism. No significant association was found between subtypes
of ADHD [combined (P = 0.46), inattentive (P = 0.41), hyperactive/impulsive (P =
0.32)] and polymorphism SCL6A2. This lack of association can also be seen in
gender in every subtype. CONCLUSIONS: The results of the study show no
significant association between norepinephrine transporter polymorphism SCL6A2
and ADHD.
PMID- 26421176
TI - Spontaneous Nontraumatic Pneumocephalus: A Case Report.
AB - INTRODUCTION: Spontaneous pneumocephalus without any pathological condition is
very rare. We described a patient with spontaneous pneumocephalus probably
arising from the relatively enlarged air-filling sphenoid sinus. CASE
PRESENTATION: A 51-year-old woman admitted Imam Reza Hospital, Mashhad, Iran with
a sudden onset of severe headache and nausea without any neurological deficit.
Brain computed tomography (CT) scan was performed to role out any pathology in
the brain. Brain CT revealed large ethmoidal and sphenoid sinuses and
disseminated intracranial pneumocephalus. A Cerebrospinal Fluid (CSF) examination
was performed to rule out meningitis. Further evaluation confirmed a small defect
in the sphenoid sinus. She has no recurrent headache or other symptoms after
about six-month follow-up. CONCLUSIONS: An extremely rare condition, a
spontaneous intracranial pneumocephalus with skull base defect origin could be
considered as a possible diagnosis in patients with sudden and severe headache.
We can safely conclude that medical treatment and close follow-up is an effective
mode of therapy in this patient.
PMID- 26421177
TI - A Meta-Analysis of Randomized Clinical Trials Comparing Shorter (Less or Equal
Than 6 Months) and Longer (More or Equal Than 12 Months) Dual Anti-Platelet
Therapy Following Drug-Eluting Coronary Stents.
AB - CONTEXT: The optimal duration of dual anti-platelet therapy (DAPT) after the
implantation of drug-eluting coronary stents (DES) is still the subject of
ongoing debate. This meta-analysis was performed to investigate the optimal
duration between <= 6 months and >= 12 months for DAPT after implantation of DES.
EVIDENCE ACQUISITION: This study was conducted at the department of cardiology,
the first college of clinical medical sciences, institute of cardiovascular
diseases of Three Gorges university during December 2014. Pub-med, Cochrane,
Scopus and clinicaltrials.gov databases were searched for papers published until
December 2014. Searches of the above databases included terms "dual anti-platelet
therapy" and "myocardial infarction (MI)" and "drug-eluting stents (DES)". All
the searched literatures were limited to Randomized Controlled Trials (RCTs).
Quality assessments were evaluated with the Jadad quality scale. Data were
extracted by two independent observers (FZ and YC). For all analyses, the 95%
confidence interval (CI) was calculated and heterogeneity of the studies was
analyzed using I2 statistics. RESULTS: Five RCTs with 9979 participants
satisfying the inclusion criteria were finally analyzed. Overall, there were 4993
patients with shorter duration of DAPT and 4986 patients with a longer treatment.
Clopidogrel was the used P2Y12 receptor inhibitor in all five RCTs. On one hand
compared to shorter duration (<= 12 months) DAPT, longer duration (>= 12 months)
did not reduce risk of mortality, cardiac death, cerebrovascular accidents,
myocardial infarction and stent thrombosis (pooled OR 1.03, 95% Confidence
Interval (CI) 0.80 - 1.32, P = 0.85, I(2) = 0%; pooled OR 0.91, 95% CI 0.64 -
1.29, P = 0.60, I(2) = 0%; pooled OR 0.84, 95% CI 0.50 - 1.42, P = 0.51, I(2) =
0%; pooled OR 1.17, 95% CI 0.87 - 1.58, P = 0.29, I(2) = 0%; pooled OR 1.36, 95%
CI 0.81 - 2.29, P = 0.24, I(2) = 0%). On the other hand, longer duration (>= 12
months) could also increase the risk of thrombolysis in myocardial infarction
(TIMI) major bleeding (pooled OR 0.50, 95% CI 0.29 - 0.85, P = 0.01, I(2) = 0%).
CONCLUSIONS: Regarding the efficacy outcomes of the patients after DES
implantation, no differences were found between shorter (<= 6 months) and longer
(>= 12 months) duration of DAPT. What is worse is that longer duration (>= 12
months) was associated with increased risk of bleeding complications.
PMID- 26421178
TI - Thyroid Hormone Profile in Patients With Acute Coronary Syndrome.
AB - BACKGROUND: Thyroid hormone has the a major role in the cardiovascular system
function and cardiac a As well as to maintain the cardiovascular homeostasis A
slightly change ind thyroid status actually affects cardiovascular mortality
hemodynamic. The background of this study was to define the prevalence of thyroid
dysfunction in acute coronary syndrome (ACS). OBJECTIVES: The primary objective
was to define the prevalence of thyroid dysfunction in acute coronary syndrome,
including Non-ST Segment Elevation Myocardial Infarction (NSTEMI), ST-segment
Elevation Myocardial Infarction (STEMI), and unstable angina groups. The
secondary objective was to determine any associations of thyroids function tests
with cardiac catheterization and mortality. PATIENTS AND METHODS: In a
prospective, observational, and cross section study, we enrolled 400 patients
admitted at the coronary care unit of King Abdulaziz University Hospital in
Jeddah, Saudi Arabia. Venous blood samples were collected from patients for the
evaluation of thyroid function (thyroids stimulating hormones, free
triiodothyronine, and free thyroxin). RESULTS: Excluding those taking thyroid
hormone preparations, 76.7% of patients admitted with acute coronary heart
disease (ST-segment elevation myocardial infarction and Non-ST segment elevation
myocardial infarction), and unstable angina had euthyroidism. Thyroid dysfunction
was reported in 23.3% of patients with coronary heart disease. Overall
hypothyroidism prevalence was 7.8%, while subclinical hyperthyroidism in our
study was 2.7%. Overt hyperthyroidism and subclinical hyperthyroidism was
reported 2.0% and 0.5%, respectively. Euthyroid sick syndrome was noticed in 41
(10.2%) of critically ill patients. The mortality rate was 9.8%; all death
patients had low triiodothyronine (T3) syndrome and were associated with
statistically significant low free triiodothyronine (FT3) (P > 0.001).
CONCLUSIONS: No significant variance was observed among patients underwent for
cardiac catheterization, STEMI, NSTEMI, unstable angina, and atrial fibrillation
with respect to FT4, FT3, and TSH levels during coronary care unit
hospitalization based on their profile data.
PMID- 26421179
TI - Relationship Between Serum Hepcidin and Ferritin Levels in Patients With
Thalassemia Major and Intermedia in Southern Iran.
AB - BACKGROUND: Hepcidin is a key regulator of iron absorption in humans. It is
mainly affected by hypoxia and iron stores. OBJECTIVES: The current study aimed
to determine the correlation between serum hepcidin and ferritin levels in
patients with Thalassemia Major (TM) and Thalassemia Intermedia (TI). PATIENTS
AND METHODS: The current cross-sectional study investigated 88 randomly selected
patients with Thalassemia, 48 TM and 40 TI, registered at the Thalassemia Clinic
of Shiraz University of Medical Sciences, a referral center for Thalassemia in
Southern Iran in 2013. All patients with TI were receiving Hydroxyurea (HU) 10 -
15 mg/kg/day for at least 10 years. The serum hepcidin, ferritin levels,
hemoglobin (Hb) and nucleated Red Blood Cell (RBC) of the two groups were
measured. RESULTS: No statistically significant correlation was observed between
serum hepcidin and ferritin levels in any of the two groups of patients with TM
(rs = 0.02, P = 0.892) or TI (rs = 0.055, P = 0.734). The median Interquartile
Range (IQR) for serum hepcidin and ferritin levels were significantly higher in
TM compared to TI group, (hepcidin: 87.6 (43.9) vs. 51.8 (23.4), P < 0.001;
ferritin: 2208 (3761) vs. 465 (632), P < 0.001). CONCLUSIONS: There was
insignificant correlation between serum hepcidin and ferritin levels in the two
groups of patients with TM and TI. It seems that regulation of hepcidin in
patients with Thalassemia is more affected by erythropoeitic activity than iron
stores. Also, hepcidin levels were significantly higher in patients with TM than
TI, possibly due to higher erythropoeitic activity in TI. In TI, it seems that
low dose HU increases Hb levels and leads to transfusion-independence, but it is
not high enough to suppress bone marrow activity and ineffective erythropoiesis.
Consequently, serum hepcidin level decreases.
PMID- 26421180
TI - Effect of Nasal Calcitonin on the Health-Related Quality of Life in Postmenopause
Women Affected With Low Bone Density.
AB - BACKGROUND: Physical activity and mental health could be affected by osteoporosis
and various therapeutic options such as calcitonin may influence Quality Of Life
(QOL) of these patients with Low Bone Density (LBD). OBJECTIVES: This study aimed
to evaluate the effect of nasal calcitonin on QOL in post menopause women with
LBD. PATIENTS AND METHODS: This clinical trial study was performed on one hundred
and fifteen menopause women with LBD less than 1 SD in Bone Mineral Densitometry
(BMD) referred to Baqiyatallah Hospital in Tehran, Iran, during 2009 - 2010. They
were assigned to receive 200 IU calcitonin nasal spray along with calcium (1000
mg) and vitamin D (400 IU) for 6 months. Quality of life was assessed by Short
Form 36 (SF-36) questionnaire (Persian-validated version). RESULTS: The mean age
(+/- SD) of the participants was 58.75 +/- 8.15 years. Intranasal spray of
calcitonin increased QOL scores significantly (88.05 +/- 15.63 vs. 92.15 +/-
13.22, P value = 0.000). Bone mineral density of spine was increased from 0.834
+/- 0.11 to 0.12 +/- 0.852 and this difference in BMD of lumbar spine was
statistically significant (P value: 0.003) but not significant in femur's BMD (P
value = 0.061). In comparison with BMD indexes, The QOL scores especially Mental
Health domain changes had only a significant correlation with the changes of
total T score in BMD (P = 0.031, Coefficient Correlation = 0.248). CONCLUSIONS:
It seems that nasal spray of calcitonin can effectively improve QOL of women with
LBD and QOL changes were not influenced by clinical or para-clinical alteration.
Mental health domain must be more considered in further studies as a predicting
domain for Health-Related Quality of Life (HR-QOL) changes.
PMID- 26421181
TI - Alternative Living Kidney Donation Programs Boost Genetically Unrelated Donation.
AB - Donor-recipient ABO and/or HLA incompatibility used to lead to donor decline.
Development of alternative transplantation programs enabled transplantation of
incompatible couples. How did that influence couple characteristics? Between 2000
and 2014, 1232 living donor transplantations have been performed. In conventional
and ABO-incompatible transplantation the willing donor becomes an actual donor
for the intended recipient. In kidney-exchange and domino-donation the donor
donates indirectly to the intended recipient. The relationship between the donor
and intended recipient was studied. There were 935 conventional and 297
alternative program transplantations. There were 66 ABO-incompatible, 68 domino
paired, 62 kidney-exchange, and 104 altruistic donor transplantations. Waiting
list recipients (n = 101) were excluded as they did not bring a living donor.
1131 couples remained of whom 196 participated in alternative programs.
Genetically unrelated donors (486) were primarily partners. Genetically related
donors (645) were siblings, parents, children, and others. Compared to
genetically related couples, almost three times as many genetically unrelated
couples were incompatible and participated in alternative programs (P < 0.001).
62% of couples were genetically related in the conventional donation program
versus 32% in alternative programs (P < 0.001). Patient and graft survival were
not significantly different between recipient programs. Alternative donation
programs increase the number of transplantations by enabling genetically
unrelated donors to donate.
PMID- 26421182
TI - Functional and Morphological Correlations before and after Video-Documented 23
Gauge Pars Plana Vitrectomy with Membrane and ILM Peeling in Patients with
Macular Pucker.
AB - Purpose. To assess functional and morphological alterations following video
documented surgery for epiretinal membranes. Methods. Forty-two patients
underwent video-documented 23-gauge vitrectomy with peeling of epiretinal (ERM)
and inner limiting membrane (ILM). Patient assessment was performed before and 3
and 6 months including best corrected visual acuity (BCVA), slit lamp
biomicroscopy, SD-OCT, and central 2 degrees and 18 degrees microperimetry. In
addition, all video-documented areas of peeling on the retinal surface were
evaluated postoperatively using an additional focal 2 degrees microperimetry.
Retinal sensitivity and BCVA were correlated with morphological changes (EZ and
ELM) in the foveal region and in regions of membrane peeling. Results. Overall,
BCVA increased from 0.6 (+/-0.2) to 0.2 (+/-0.2) logMAR after 6 months with an
increase in retinal sensitivity (17.9 +/- 2.7 dB to 26.8 +/- 3.1 dB, p < 0.01).
We observed a significant correlation between the integrity of the EZ but not of
the ELM and the retinal sensitivity, overall and in peeling areas (p < 0.05).
However, no significant correlation between alterations in the area of peeling
and overall retinal sensitivity regarding visual acuity gain could be observed
after 6 months (p > 0.05). In contrast, overall postoperative retinal sensitivity
was significantly decreased in patients with a visual acuity gain lower than 2
lines (p < 0.05) correlating with EZ defects seen in OCT. Conclusions. Mechanical
trauma of epiretinal membrane and ILM peeling due to the use of intraocular
forceps may affect the outer retinal structure. Nevertheless, these changes seem
to have no significant impact on postoperative functional outcome.
PMID- 26421184
TI - Hepatic but Not CNS-Expressed Human C-Reactive Protein Inhibits Experimental
Autoimmune Encephalomyelitis in Transgenic Mice.
AB - We recently demonstrated that human C-reactive protein (CRP), expressed
hepatically in transgenic mice (CRPtg), improved the outcome of experimental
autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS).
The liver is the primary site of CRP synthesis in humans and in CRPtg mice but is
also expressed by both at low levels in the CNS. To determine if CNS expression
of human CRP is sufficient to impact EAE, we generated neuronal CRP transgenic
mice (nCRPtg) wherein human CRP expression is driven by the neuron-specific
Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) gene promoter.
We found that hepatically expressed/blood-borne CRP, but not CNS expressed CRP,
lessened EAE severity. These outcomes indicate that the protective actions of
human CRP in EAE are manifested in the periphery and not in the CNS and reveal a
previously unappreciated site specificity for the beneficial actions of CRP in
CNS disease.
PMID- 26421183
TI - Retinal Changes Induced by Epiretinal Tangential Forces.
AB - Two kinds of forces are active in vitreoretinal traction diseases: tangential and
anterior-posterior forces. However, tangential forces are less characterized and
classified in literature compared to the anterior-posterior ones. Tangential
epiretinal forces are mainly due to anomalous posterior vitreous detachment
(PVD), vitreoschisis, vitreopapillary adhesion (VPA), and epiretinal membranes
(ERMs). Anomalous PVD plays a key role in the formation of the tangential
vectorial forces on the retinal surface as consequence of gel liquefaction
(synchysis) without sufficient and fast vitreous dehiscence at the vitreoretinal
interface. The anomalous and persistent adherence of the posterior hyaloid to the
retina can lead to vitreomacular/vitreopapillary adhesion or to a formation of
avascular fibrocellular tissue (ERM) resulting from the proliferation and
transdifferentiation of hyalocytes resident in the cortical vitreous remnants
after vitreoschisis. The right interpretation of the forces involved in the
epiretinal tangential tractions helps in a better definition of diagnosis,
progression, prognosis, and surgical outcomes of vitreomacular interfaces.
PMID- 26421185
TI - Green Space and Child Weight Status: Does Outcome Measurement Matter? Evidence
from an Australian Longitudinal Study.
AB - OBJECTIVE: To examine whether neighbourhood green space is beneficially
associated with (i) waist circumference (WC) and (ii) waist-to-height ratio
(WtHR) across childhood. METHODS: Gender-stratified multilevel linear regressions
were used to examine associations between green space and objective measures of
weight status in the Longitudinal Study of Australian Children, a nationally
representative source of data on 4,423 children aged 6 y to 13 y. WC and WtHR
were measured objectively. Percentage green space within the local area of
residence was calculated. Effect modification by age was explored, adjusting for
socioeconomic confounding. RESULTS: Compared to peers with 0-5% green space
locally, boys and girls with >40% green space tended to have lower WC (beta boys
-1.15, 95% CI -2.44, 0.14; beta girls -0.21, 95% CI -1.47, 1.05) and WtHR (beta
boys -0.82, 95% CI -1.65, 0.01; beta girls -0.32, 95% CI -1.13, 0.49).
Associations among boys were contingent upon age (p valuesage*green space <
0.001) and robust to adjustment for socioeconomic variables. The benefits of
greener neighbourhoods appeared from age 7, with mean WC and WtHR for boys aged
13 y with >40% green space at 73.85 cm and 45.75% compared to those with 0-5%
green space at 75.18 cm and 46.62%, respectively. CONCLUSIONS: Greener
neighbourhoods appear beneficial to alternative child weight status measures,
particularly among boys.
PMID- 26421186
TI - Development of Delirium in the Intensive Care Unit in Patients after Endovascular
Aortic Repair: A Retrospective Evaluation of the Prevalence and Risk Factors.
AB - Delirium is an acute form of nervous system dysfunction often observed in
patients in the intensive care unit. Endovascular aortic repair (EVAR) is
considered a minimally invasive surgical treatment for abdominal aortic aneurysm.
Although the operation method is widely used, there are few investigations of the
rate and risk factors of delirium development after the operation. In this study,
we retrospectively examined the rate of delirium development in the intensive
care unit (ICU) after EVAR, as well as the associated preoperative risk factors
and effects on the lengths of ICU and hospital stays. We examined the 81
consecutive patients who underwent elective EVAR between November 2013 and August
2014. The Intensive Care Delirium Screening Checklist was used to diagnose
delirium. Twenty patients (24.7%) were diagnosed with delirium in this study. The
ICU and hospital length of stays of patients with delirium were 3.3 +/- 2.4 days
and 14.5 +/- 11.9 days, respectively, the latter of which was significantly
longer than that of patients without delirium (p = 0.019). Additionally, renal
dysfunction, preoperative benzodiazepine use, and intraoperative transfusion were
found to be risk factors for the development of delirium after elective EVAR.
PMID- 26421187
TI - Soft Tissue Masses of Hand: A Radio-Pathological Correlation.
AB - Aim. To evaluate soft tissue masses of the hand with magnetic resonance imaging
(MRI) and ultrasonography (USG) and to correlate imaging findings with
pathological findings. Material and Methods. Thirty-five patients with soft
tissue masses of the hand were evaluated with high resolution USG and contrast
enhanced MRI of the hand, prospectively over a period of 2.5 years. The
radiological diagnosis was then compared with cytology/histopathology. Results.
There were a total of 19 (55%) females. The mean age was 27.45 +/- 14.7 years.
Majority (45%) of cases were heteroechoic. Four cases were predominantly
hyperechoic. These were later diagnosed as lipomas. Four cases were anechoic
(diagnosed as ganglions). Only four lesions showed hyperintense signal on T1
weighted images. Out of these, 3 were lipomas and one was cavernous haemangioma.
Three lesions were hypointense on T2-weighted images. All these lesions were
diagnosed as giant cell tumor of the tendon sheath. A correct diagnosis was
possible on MRI in 80% of cases (n = 28). Conclusion. MRI provides specific
findings for diagnosis of certain soft tissue lesions of the hand.
Ultrasonography allows accurate diagnosis of hemangioma/vascular malformations.
However, in most conditions, imaging findings are nonspecific and diagnosis rests
on pathologic evaluation.
PMID- 26421188
TI - Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as
Shown by Quantitative Proteomics of HeLa Cells.
AB - Hypoxia is an important and common characteristic of many human tumors. It is a
challenge clinically due to the correlation with poor prognosis and resistance to
radiation and chemotherapy. Understanding the biochemical response to hypoxia
would facilitate the development of novel therapeutics for cancer treatment.
Here, we investigate alterations in gene expression in response to hypoxia by
quantitative proteome analysis using stable isotope labeling with amino acids in
cell culture (SILAC) in conjunction with LCMS/MS. Human HeLa cells were kept
either in a hypoxic environment or under normoxic conditions. 125 proteins were
found to be regulated, with maximum alteration of 18-fold. In particular, three
clusters of differentially regulated proteins were identified, showing
significant upregulation of glycolysis and downregulation of mitochondrial
ribosomal proteins and translocases. This interaction is likely orchestrated by
HIF-1. We also investigated the effect of hypoxia on the cell cycle, which shows
accumulation in G1 and a prolonged S phase under these conditions. Implications.
This work not only improves our understanding of the response to hypoxia, but
also reveals proteins important for malignant progression, which may be targeted
in future therapies.
PMID- 26421189
TI - Favorable Outcomes after Implantation of Biodegradable Polymer Coated Sirolimus
Eluting Stents in Diabetic Population: Results from INDOLIMUS-G Diabetic
Registry.
AB - Objective. The main aim is to evaluate safety, efficacy, and clinical performance
of the Indolimus (Sahajanand Medical Technologies Pvt. Ltd., Surat, India)
sirolimus-eluting stent in high-risk diabetic population with complex lesions.
Methods. It was a multicentre, retrospective, non-randomized, single-arm study,
which enrolled 372 diabetic patients treated with Indolimus. The primary endpoint
of the study was major adverse cardiac events (MACE), which is a composite of
cardiac death, target lesion revascularization (TLR), target vessel
revascularization (TVR), myocardial infarction (MI), and stent thrombosis (ST).
The clinical follow-ups were scheduled at 30 days, 6 months, and 9 months.
Results. The mean age of the enrolled patients was 53.4 +/- 10.2 years. A total
of 437 lesions were intervened successfully with 483 stents (1.1 +/- 0.3 per
lesion). There were 256 (68.8%) male patients. Hypertension and totally occluded
lesions were found in 202 (54.3%) and 45 (10.3%) patients, respectively. The
incidence of MACE at 30 days, 6 months and 9 months was 0 (0%), 6 (1.6%), and 8
(2.2%), respectively. The event-free survival at 9-month follow-up by Kaplan
Meier method was found to be 97.8%. Conclusion. The use of biodegradable polymer
coated sirolimus-eluting stent is associated with favorable outcomes. The results
demonstrated in our study depict its safety and efficacy in diabetic population.
PMID- 26421190
TI - Medical History of Elderly Patients in the Emergency Setting: Not an Easy Point
of-Care Diagnostic Marker.
AB - Background. Medical histories are a crucially important diagnostic tool. Elderly
patients represent a large and increasing group of emergency patients. Due to
cognitive deficits, taking a reliable medical history in this patient group can
be difficult. We sought to evaluate the medical history-taking in emergency
patients above 75 years of age with respect to duration and completeness.
Methods. Anonymous data of consecutive patients were recorded. Times for the
defined basic medical history-taking were documented, as were the availability of
other sources and times to assess these. Results. Data of 104 patients were
included in the analysis. In a quarter of patients (25%, n = 26) no complete
basic medical history could be obtained. In the group of patients where complete
data could be gathered, only 16 patients were able to provide all necessary
information on their own. Including other sources like relatives or GPs prolonged
the time until complete medical history from 7.3 minutes (patient only) to 26.4
(+relatives) and 56.3 (+GP) minutes. Conclusions. Medical histories are important
diagnostic tools in the emergency setting and are prolonged in the elderly,
especially if additional documentation and third parties need to be involved. New
technologies like emergency medical cards might help to improve the availability
of important patient data but implementation of these technologies is costly and
faces data protection issues.
PMID- 26421191
TI - An Additive Effect of Oral N-Acetyl Cysteine on Eradication of Helicobacter
pylori.
AB - Background. Helicobacter pylori is highly adapted to the gastric environment
where it lives within or beneath the gastric mucous layer. The aim of this study
was to evaluate whether the addition of N-acetyl cysteine to the treatment
regimen of H. pylori infection would affect eradication rates of the disease.
Methods. A total of 79 H. pylori positive patients were randomized to two
therapeutic groups. Both groups received a 14-day course of three-drug regimen
including amoxicillin/clarithromycin/omeprazole. Experimental group (38 subjects)
received NAC, and control group (41 subjects) received placebo, besides three
drug regimen. H. pylori eradication was evaluated by urea breath test at least 4
weeks after the cessation of therapy. Results. The rate of H. pylori eradication
was 72.9% and 60.9% in experimental and control groups, respectively (P = 0.005).
By logistic regression modeling, female gender (OR 3.68, 95% CI: 1.06-5.79; P =
0.040) and treatment including NAC (OR 1.88, 95% CI: 0.68-3.15; P = 0.021) were
independent factors associated with H. pylori eradication. Conclusion. The
results of the present study show that NAC has an additive effect on the
eradication rates of H. pylori obtained with three-drug regimen and appears to be
a promising means of eradicating H. pylori infection.
PMID- 26421192
TI - Effect of Perioperative beta-Blockers on Pulmonary Complications among Patients
with Chronic Obstructive Pulmonary Disease Undergoing Lung Resection Surgery.
AB - The aim of this study is to determine if COPD patients undergoing lung resection
with perioperative beta-blocker use are more likely to suffer postoperative COPD
exacerbations than those that did not receive perioperative beta-blockers.
Methods. A historical cohort study of COPD patients, undergoing lung resection
surgery at Memorial Sloan-Kettering Cancer Center between 2002 and 2006. Primary
outcomes were the rate of postoperative COPD exacerbations, defined as any
initiation or increase of glucocorticoids for documented bronchospasm. Results.
520 patients with COPD were identified who underwent lung resection. Of these,
205 (39%) received perioperative beta-blockers and 315 (61%) did not. COPD was
mild among 361 patients (69% of all patients), moderate in 117 patients (23%),
and severe in 42 patients (8%). COPD exacerbations occurred among 11 (5.4%)
patients who received perioperative beta-blockers and among 20 (6.3%) patients
who did not. Secondary outcomes, which included respiratory failure, 30-day
mortality, and the presence or absence of any cardiovascular complication, ICU
transfer, cardiovascular complication, or readmission within 30 days, did not
differ in prevalence between the two groups. Conclusions. This study implies that
perioperative beta-blockers use among COPD patients undergoing lung resection
surgery does not impact the rate of exacerbations.
PMID- 26421193
TI - Retrospective Clinical and Radiological Outcomes after Robotic Assisted
Bicompartmental Knee Arthroplasty.
AB - Purpose. Bicompartmental knee arthroplasty (BiKA) is a favorable alternative to
total knee arthroplasty for degenerative disease limited to two knee
compartments. Recently developed robotic-assisted systems improved the clinical
efficacy of unicompartmental knee arthroplasty by providing enhanced component
positioning with dynamic ligament balancing. The purpose of this study was to
evaluate the short-term outcomes of patients, undergoing bicompartmental knee
arthroplasty at a single institution by a single surgeon using a robotic-assisted
system. It was hypothesized that robotic assisted BiKA is a prevailing choice for
degenerative disease limited to two knee compartments with good functional
results. Methods. A search of the institution's joint registry was conducted to
identify patients that underwent robotic-assisted BiKA of the patellofemoral
compartment and the medial or lateral compartment. Results. A total number of 29
patients (30 BiKA) with a mean age of 63.6 years were identified who received a
patellofemoral resurfacing in combination with medial or lateral compartment
resurfacing. Twenty-four out of 29 patients had good to excellent outcome.
Conclusion. Robotic assisted bicompartmental arthroplasty using broad indications
and only excluding patients with severe deformity and those that have less than 4
mm of joint space in the surviving compartment demonstrated 83% good to excellent
results.
PMID- 26421194
TI - Brain and Behavior Plasticity: From Fundamental Science to Health Outcomes.
PMID- 26421195
TI - Isolated Right Ventricular Myocarditis: Rarely Reported Pathology.
AB - Objective. Preventing the morbidity and mortality from isolated right ventricular
myocarditis by its early recognition and treatment. Background. The clinical
presentation of myocarditis ranges from nonspecific systemic symptoms (fever,
myalgia, palpitations, or exertional dyspnea) to fulminant cardiac failure and
sudden death. In our case, echocardiography raised the possibility of myocarditis
at an early stage, although the signs and symptoms did not indicate right
ventricular disease. Review of the literature showed only 4 previous reports, all
diagnosed at autopsy, in which diagnosis was not suspected in vivo.
Design/Methods. We are reporting case of a 23-year-old male with no past medical
history who presented to emergency room with a nonexertional sharp left sided
chest pain. Diagnostic tests were conducted, which revealed elevated troponins,
decreased right ventricular ejection function but preserved left ventricular
function, and no evidence of coronary artery disease. Results. A diagnosis of
isolated right ventricular myocarditis was made on the basis of clinical,
echocardiographic, and cardiac MRI findings. Conclusions. Isolated right
ventricular myocarditis should be suspected in a patient with depressed right
ventricular function without left ventricular involvement on echocardiography and
cardiac MRI, elevated cardiac enzymes, and no evidence of coronary artery
disease.
PMID- 26421196
TI - Riga-Fede Disease Associated with Natal Teeth: Two Different Approaches in the
Same Case.
AB - Natal teeth are those present in the oral cavity at the child's birth. These
teeth can cause ulcers on the ventral surface of the tongue, lip, and the
mother's breast characterizing the Riga-Fede Disease. The treatment depends on
the tooth's mobility and the risk of aspiration or swallowing; whether it is
supernumerary or regular primary teeth; whether it is causing interference in
breastfeeding; breast and oral soft tissue injuries; and the general state of
child's health. A 1-month-old female infant was diagnosed with two natal teeth
and an ulcerated lesion on the ventral surface of the tongue, leading to the
clinical diagnosis of Riga-Fede Disease. The treatment performed consisted of the
maintenance of the natal tooth that showed no increased mobility, adding a small
increment of glass ionomer cement to its incisal edge, and orientation for
hygiene with saline solution. Due to the increased mobility of the other natal
tooth, surgical removal was performed. There was regular monitoring of the
patient and complete wound healing was observed after 15 days. The proposed
treatment was successful and the patient is still in follow-up without recurrence
of the lesion after one year.
PMID- 26421197
TI - Management of a Periodontal Pocket Using a Removable Orthodontic Appliance and
Nonsurgical Periodontal Therapy.
AB - Purpose. As documented in the literature, bony defects can be managed by an
orthodontic approach. Methods. This case report describes the treatment of a bony
defect caused by orthodontic malposition through phase I periodontal therapy and
a simple removable orthodontic appliance used for the first time in a 20-year-old
girl. Results. The periodontal pocket was reduced from 8 mm to 3 mm shortly after
treatment. Conclusion. This case report concludes that orthodontic therapy can be
used successfully in treatment of bony defects caused by mesially tilted molars.
PMID- 26421198
TI - Solitary Peripheral Osteoma of the Angle of the Mandible.
AB - Solitary peripheral osteoma is a benign, slow-growing osteogenic tumor arising
from craniofacial bones such as the sinus, temporal, or jaw bones but rarely
originating from the mandible. Osteoma consists of compact or cancellous bone
that may be of peripheral, central, or extraskeletal type. Peripheral osteoma
arises from the periosteum and is commonly a unilateral, pedunculated mushroom
like mass. Solitary peripheral osteomas are characterized by well-defined,
rounded, or oval radiopaque mass in the computed tomography. Although multiple
osteomas of the jaws are a hallmark of Gardner's syndrome (familial adenomatous
polyposis), nonsyndromic cases are typically solitary. Herein, we report a rare
case of solitary peripheral osteoma of the angle of the mandible in a 27-year-old
female with clinical, radiologic, and histopathologic findings.
PMID- 26421199
TI - Recurrent Episodes of Thyrotoxicosis in a Man following Pregnancies of his Spouse
with Hashimoto's Thyroiditis.
AB - Over an 8-year period, a male patient presented three times to an endocrinologist
with strikingly similar presentations, including palpitations, anxiety, and
tremors. Each of his presentations occurred following either the birth of one of
his two children or his wife's late termination of pregnancy. This patient's
illness followed the typical time course of silent thyroiditis: hyperthyroidism,
followed by euthyroidism, a late hypothyroid phase, and then a complete
resolution of symptoms and normalization of thyroid function tests over a period
of several months. We discuss the curious clinical presentation, diagnostic
evaluation, and a literature review of alternate explanations for this patient's
condition, including a discussion of the impact of seasonal shift, spousal's
autoimmune disease, stress, and evolutionary changes in males postpartum.
Although the differential diagnosis is broad in this case and the thyrotoxicosis
could have coincidentally followed pregnancies of the patient's wife, documented
hormonal changes in men during postpartum period in conjunction with the timeline
of the patient's condition are suggestive of recurrent "sympathetic" postpartum
thyroiditis. To our knowledge, this is the first case report of recurrent
painless thyroiditis in a man following pregnancies of his wife with Hashimoto's
thyroiditis.
PMID- 26421200
TI - Bilateral Intracranial Vertebral Artery Stenosis Presenting as Recurrent
Prolonged Presyncopal Episodes.
AB - Amongst various mechanisms of presyncopal events, posterior circulation disease
needs to be considered. This particular mechanism has been underrecognized. We
describe a case of a 76-year-old patient with recurrent posterior circulation
TIAs, presenting as recurrent prolonged presyncopal events.
PMID- 26421201
TI - Modulation of the Left Prefrontal Cortex with High Frequency Repetitive
Transcranial Magnetic Stimulation Facilitates Gait in Multiple Sclerosis.
AB - Multiple Sclerosis (MS) is a chronic central nervous system (CNS) demyelinating
disease. Gait abnormalities are common and disabling in patients with MS with
limited treatment options available. Emerging evidence suggests a role of
prefrontal attention networks in modulating gait. High-frequency repetitive
transcranial magnetic stimulation (rTMS) is known to enhance cortical
excitability in stimulated cortex and its correlates. We investigated the effect
of high-frequency left prefrontal rTMS on gait parameters in a 51-year-old
Caucasian male with chronic relapsing/remitting MS with residual disabling
attention and gait symptoms. Patient received 6 Hz, rTMS at 90% motor threshold
using figure of eight coil centered on F 3 location (using 10-20
electroencephalography (EEG) lead localization system). GAITRite gait analysis
system was used to collect objective gait measures before and after one session
and in another occasion three consecutive daily sessions of rTMS. Two-tailed
within subject repeated measure t-test showed significant enhancement in
ambulation time, gait velocity, and cadence after three consecutive daily
sessions of rTMS. Modulating left prefrontal cortex excitability using rTMS
resulted in significant change in gait parameters after three sessions. To our
knowledge, this is the first report that demonstrates the effect of rTMS applied
to the prefrontal cortex on gait in MS patients.
PMID- 26421202
TI - Coincidence of Incomplete Pentalogy of Cantrell and Meningomyelocele in a
Dizygotic Twin Pregnancy.
AB - Pentalogy of Cantrell is an extremely rare and lethal syndrome. Ectopia cordis is
frequently found in fetuses with POC but not required for incomplete forms.
Likewise, meningomyelocele is a relatively uncommon neural tube defect affecting
central nervous system and associated with neurological problems. Herein, we
presented a woman with dizygotic twin pregnancy having coincidence of incomplete
POC and MMC in each individual fetus, which has never been reported previously.
PMID- 26421203
TI - Benign Lymphoid Hyperplasia Presenting as Bilateral Scleral Nodules.
AB - Purpose. To report a case of transient lymphoid hyperplasia presenting as
bilateral nodular scleral mass in a young male patient. Design. Observational
case report. Methods. Chart review. Causes of scleritis were considered and
excluded based on detailed history, physical examination, and laboratory
investigations. Results. Excisional biopsy of scleral lesions indicated lymphoid
tissue. Immunohistochemical studies revealed a polyclonal population of T and B
cells consistent with a benign reactive process. Conclusions. Chronic exposure of
the ocular adnexa to many allergens and irritants may lead to activation of the
inflammatory cascade. In severely allergic patients activation may be exponential
and elicit an immune-mediated response resulting in a transient lymphoid reactive
process.
PMID- 26421204
TI - Adie's Tonic Pupil in Systemic Sclerosis: A Rare Association.
AB - We report a rare association of Adie's tonic pupil in a patient with systemic
sclerosis who was otherwise systemically stable. This paper is an effort to
unravel whether the tonic pupil and systemic sclerosis are an association by
chance (which may be the case) or systemic sclerosis is the source of the tonic
pupil.
PMID- 26421205
TI - Iliac Crest Avulsion Fracture in a Young Sprinter.
AB - Avulsion fracture of the iliac crest is an uncommon pathology. It usually occurs
in teenagers during sport activities, more common in boys. We report a case of 16
year-old male competitive sprinter, who had an avulsion of a part of the iliac
crest and the anterior-superior iliac spine during a competition. The traumatism
occurred during the period of acceleration phase out of the blocks which
corresponds to the maximum traction phase on the tendons. Then a total loss of
function of the lower limb appears forcing him to stop the run. X-ray and CT scan
confirmed the rare diagnosis of avulsion of the quasitotality of the iliac crest
apophysis, corresponding to Salter 2 fracture. We performed an open reduction and
internal fixation with two screws, allowing a return to sport after 3 months and
his personal best record in the 100 meters at the 6th postoperative month.
PMID- 26421206
TI - Mucinous Bladder Adenocarcinoma: Case Report and Literature Review.
AB - Primary mucinous adenocarcinoma is an extremely rare type of bladder cancer, with
aggressive behavior and poor response to chemotherapy and radiotherapy. The
symptoms are similar to those of other bladder tumors. Surgery is the main
treatment and remains the only curative option. There may be a progression from
mucinous metaplasia to mucinous adenoma and then mucinous adenocarcinoma. We
present the case of a 40-year-old woman with recurrent lower urinary tract
infections, submitted to imaging tests, which showed a bladder tumor. After
transurethral resection, pathology showed intestinal mucinous carcinoma.
Metastatic work-up was negative. New surgical procedure showed metaplasia but no
recurrence of the carcinoma. The patient is now using antibiotic prophylaxis and
will undergo a cystoscopy every 3 months and computed tomography in one year.
PMID- 26421207
TI - Successful Treatment of Acute on Chronic Mesenteric Ischaemia by Common Iliac to
Inferior Mesenteric Artery Bypass.
AB - Chronic mesenteric ischaemia is a rare and potentially fatal condition most
commonly due to atherosclerotic stenosis or occlusion of two or more mesenteric
arteries. Multivessel revascularisation of both primary mesenteric vessels, the
celiac artery and superior mesenteric artery (SMA), is the current mainstay of
treatment; however, in a certain cohort of patients, revascularisation one or
both vessels may not be possible. Arteries may be technically unreconstructable
or the patient may be surgically unfit for the prolonged aortic cross clamping
times required. Here we present a case involving a 72-year-old woman with acute
on chronic mesenteric ischaemia. She was a high risk surgical patient with severe
unreconstructable stenotic disease of the SMA and celiac arteries. She was
successfully treated with single vessel revascularisation of the inferior
mesenteric artery (IMA) via a common iliac to IMA reversed vein bypass. At two
year follow-up, the graft remains patent and the patient continues to be symptom
free and is maintaining her weight.
PMID- 26421209
TI - MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in
Parkinson's Disease.
AB - Background. Thalamotomy is effective in alleviating tremor in Parkinson's disease
(PD). Methods. Seven PD patients, mean age 59.4 +/- 9.8 years (range, 46-74) with
a mean disease duration of 5.4 +/- 2.8 years (range, 2-10) suffering from severe
refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI
guided focused ultrasound (MRgFUS), an innovative technology that enables
noninvasive surgery. Results. Tremor stopped in the contralateral upper extremity
in all patients immediately following treatment. Total UPDRS decreased from 37.4
+/- 12.2 to 18.8 +/- 11.1 (p = 0.007) and PDQ-39 decreased from 42.3 +/- 16.4 to
21.6 +/- 10.8 (p = 0.008) following MRgFUS. These effects were sustained (mean
follow-up 7.3 months). Adverse events during MRgFUS included headache (n = 3),
dizziness (n = 2), vertigo (n = 4), and lip paresthesia (n = 1) and following
MRgFUS were hypogeusia (n = 1), unsteady feeling when walking (n = 1, resolved),
and disturbance when walking tandem (n = 1, resolved). Conclusions. Thalamotomy
using MRgFUS is safe and effective in PD patients. Large randomized studies are
needed to assess prolonged efficacy and safety.
PMID- 26421210
TI - Effect of GBA Mutations on Phenotype of Parkinson's Disease: A Study on Chinese
Population and a Meta-Analysis.
AB - GBA has been identified as a genetic risk factor for PD. Whether the clinical
manifestations of PD patients with or without GBA mutations are different has
still not reached a consensus. We firstly detected the GBA mutation L444P in 1147
Chinese PD patients and simultaneously evaluated their corresponding clinical
data. Then we compared the phenotypes between 646 PD patients with GBA mutations
and 10344 PD patients without GBA mutations worldwide through meta-analysis.
Through the method of meta-analysis, there was significant difference in age at
onset (MD = -3.10 [95% CI: -4.88, -1.32]), bradykinesia as an initial symptom (OR
= 1.49 [95% CI: 1.15, 1.94]), having family history (OR = 1.50 [95% CI: 1.18,
1.91]), and dementia (OR = 3.21 [95% CI: 1.97, 5.24]) during the comparison
between PD patients with and without GBA mutations. While, in the aspect of
tremor as an initial symptom (OR = 0.81 [95% CI: 0.64, 1.03]), the severity of
motor symptoms such as H-Y (MD = 0.06 [95% CI: -0.06, 0.17]) and UPDRS-III (MD =
1.61 [95% CI: -0.65, 3.87]) and having dyskinesia (OR = 1.60 [95% CI: 0.90,
2.84]) during the comparison between the two groups revealed no statistical
differences. Our results suggested that the phenotypes of PD patients with GBA
mutations are different from GBA noncarriers.
PMID- 26421208
TI - Evolutionary Consequences of Male Driven Sexual Selection and Sex-Biased Fitness
Modifications in Drosophila melanogaster and Members of the simulans Clade.
AB - Males have evolved a variety of behavioral, morphological, and physiological
traits to manipulate their mates in order to maximize their chances of success.
These traits are bound to influence how females respond to male behaviors and
influence the nature of sexual selection/conflict. A common consequence of
aggressive male mating strategies in Drosophila melanogaster is the reduction of
female lifespan. Our study shows that this is common across members of the
simulans clade. Reduced life expectancy of females implies that female
contribution to a population is less than that of males per generation. Fitness
differences between the sexes in every generation will invariably affect overall
population fitness. How natural selection responds to the female deaths and
thereby the unequal fitness of the sexes has rarely been addressed. We shed light
on this issue and provide evidence, which suggests that additional gains of
fitness by males due to their longevity and continued mating may provide one
explanation as to why the loss of female fitness may be "invisible" (effectively
neutral) to natural selection. Male driven sexual selection and additional,
transgenerational gains of male fitness can be an important force of evolutionary
change and need to be tested with other organisms.
PMID- 26421211
TI - A Novel Analytical Method for Trace Ammonium in Freshwater and Seawater Using 4
Methoxyphthalaldehyde as Fluorescent Reagent.
AB - A novel fluorescent reagent for determination of ammonium, 4
methoxyphthalaldehyde (MOPA), was successfully synthesized in this study. Under
alkaline conditions, MOPA could reacted with ammonium rapidly at room
temperature, producing fluorescent substance which had maximum excitation at 370
nm and emission wavelength at 454 nm. Based on this, a novel fluorescence
analysis method was established for the determination of trace ammonium in
natural water. Experimental parameters including reagent concentration, pH,
reaction equilibrium time, and metal ions masking agent were optimized. The
results showed that the optimized MOPA concentration was 0.12 g/L, pH was in the
range of 11.2-12.0, and sulfite concentration was 0.051 g/L, respectively. Metal
ions masking agent had no obvious effect on the fluorescence signal. With the
reaction time of 15 minutes, linear range of this method was between 0.025 and
0.300 MUmol/L, and the method detecting limit was 0.0058 MUmol/L. The matrix
recovery of the proposed method was in the range of 93.6-108.1%. Compared with
the OPA method, this method was much more sensitive and rapid without the
interference of background peak and would be more suitable for developing a
portable fluorescence detection system.
PMID- 26421212
TI - Ex vivo 3D osteocyte network construction with primary murine bone cells.
AB - Osteocytes reside as three-dimensionally (3D) networked cells in the
lacunocanalicular structure of bones and regulate bone and mineral homeostasis.
Despite of their important regulatory roles, in vitro studies of osteocytes have
been challenging because: (1) current cell lines do not sufficiently represent
the phenotypic features of mature osteocytes and (2) primary cells rapidly
differentiate to osteoblasts upon isolation. In this study, we used a 3D
perfusion culture approach to: (1) construct the 3D cellular network of primary
murine osteocytes by biomimetic assembly with microbeads and (2) reproduce ex
vivo the phenotype of primary murine osteocytes, for the first time to our best
knowledge. In order to enable 3D construction with a sufficient number of viable
cells, we used a proliferated osteoblastic population of healthy cells outgrown
from digested bone chips. The diameter of microbeads was controlled to: (1)
distribute and entrap cells within the interstitial spaces between the microbeads
and (2) maintain average cell-to-cell distance to be about 19 um. The entrapped
cells formed a 3D cellular network by extending and connecting their processes
through openings between the microbeads. Also, with increasing culture time, the
entrapped cells exhibited the characteristic gene expressions (SOST and FGF23)
and nonproliferative behavior of mature osteocytes. In contrast, 2D-cultured
cells continued their osteoblastic differentiation and proliferation. This 3D
biomimetic approach is expected to provide a new means of: (1) studying flow
induced shear stress on the mechanotransduction function of primary osteocytes,
(2) studying physiological functions of 3D-networked osteocytes with in vitro
convenience, and (3) developing clinically relevant human bone disease models.
PMID- 26421213
TI - Urine Club Cell 16-kDa Secretory Protein and Childhood Wheezing Illnesses After
Lower Respiratory Tract Infections in Infancy.
AB - Background: Infants with lower respiratory tract infections (LRTIs) are at an
increased risk of developing childhood wheezing illnesses (including asthma), but
it is not currently possible to predict those at risk for these long-term
outcomes. The current objective was to examine whether urine levels of club cell
16-kDa secretory protein (CC16) at the time of an infant LRTI are associated with
the development of childhood wheezing illnesses. Methods: Prospective study of
133 previously healthy infants enrolled during a healthcare visit for a LRTI and
followed longitudinally for childhood wheezing illnesses. Urine levels of CC16 at
the time of enrollment were measured after validating a commercially available
enzyme-linked immunosorbent assay kit for serum. The outcome of interest was
parental report of subsequent childhood wheeze (defined as >=1 episode of
wheezing following the initial LRTI) at the 1-year follow-up visit. Logistic
regression was used for the main analysis. Results: The median (interquartile
range) urine levels of CC16 (ng/mg of creatinine) at the time of an infant LRTI
were 11.1 (7.7-20.1) for infants with subsequent childhood wheeze and 13.4 (8.3
61.1) for those without (p = 0.11). In the main multivariate analysis using a
logarithmic transformation of the urine levels of CC16, a twofold increase in
urine levels of CC16 was associated with ~30% decreased odds (OR = 0.74 [95%
confidence interval (CI) 0.56-0.98], p = 0.04) of subsequent childhood wheeze
after adjustment for potential confounders. Conclusions: An inverse association
was found between urine levels of CC16 at the time of an infant LRTI and the odds
of subsequent childhood wheeze. Urine CC16 may be a useful biomarker of the
development of childhood wheezing illnesses after LRTIs in infancy.
PMID- 26421214
TI - Application of an Asthma Screening Questionnaire in Children with Sickle Cell
Disease.
AB - Objective: Asthma in sickle cell disease (SCD) patients is associated with
elevated morbidity and mortality. Early detection and initiation of treatment may
therefore lead to improved outcome. Utility of an asthma screening questionnaire
to identify obstructive airway disease and physician diagnosed asthma in children
with SCD at an outpatient setting as an effective, easy-to-administer screening
tool has not previously been evaluated in this population. Methods: A previously
validated asthma screening questionnaire and spirometry were prospectively
administered to 41 SCD children at a routine clinic visit. Results: Prevalence of
obstructive airway was 51.2% (n = 21) and physician diagnosis of asthma 33.3% (n
= 13). Sensitivity (40%) and specificity (75%) of the questionnaire was poor in
detecting obstructive airway disease, but sensitivity (77%), specificity (100%),
positive predictive value (100%), and negative predictive value (90%) were high
in detecting physician diagnosis of asthma. Conclusion: An asthma screening
questionnaire could be a useful tool in identifying at-risk SCD children who may
benefit from further management.
PMID- 26421215
TI - Adolescent Asthma Pharmacotherapy in a State of Flux.
AB - Recently, the United States Food and Drug Administration (FDA) elected not to
approve a once-daily inhaled corticosteroid/long-acting beta2 agonist combination
product in 12-17-year-old patients due to lack of sufficient data, despite
approval of previous combination products with similar levels of supporting
evidence. As the FDA's stance toward adolescent data is changing, the opportunity
to learn about their response to asthma medication has now arisen. A review of
the relevant issues pertinent to pharmacotherapy of asthma in the 12-17-year-old
population is discussed in this review.
PMID- 26421216
TI - A case of intravascular lymphoma presenting as myelopathy diagnosed with a skin
biopsy.
AB - BACKGROUND: Intravascular lymphoma (IVL) is a rare subtype of non-Hodgkin
lymphoma with exclusively or predominantly intravascular proliferation. Without
therapeutic intervention, the neurologic involvement is rapidly progressive and
inevitably fatal. Most of the IVL patients have prominent or exclusive
manifestations in the nervous system and there are several reports of patients
presenting with spinal symptoms. CASE DESCRIPTION: A 68-year-old male patient
admitted with the complaints of progressive paraparesis. T2-weighted magnetic
resonance imaging (MRI) of the spinal cord showed hyperintense lesions in the
thoracic cord. A diagnosis of myelitis of unknown etiology was assumed, and
steroid pulse therapy was administered, which temporarily improved the patient's
symptoms. However, the paraparesis recurred, and other symptoms, such as vertigo,
psychosis, and seizures, developed 1-month after the initial treatment. Multiple
high-intensity lesions were detected in the bilateral subcortical white matter on
DW MRI. Based on the patient's clinical course, IVL was suspected; however,
obtaining histological confirmation was not possible, as no Gd-enhanced brain or
spinal lesions were identified and repeated cerebrospinal fluid examinations were
negative for tumor cells. Therefore, a random skin biopsy was performed, and IVL
was diagnosed. Obtaining a comparatively favorable outcome was possible owing to
the subsequent administration of R-CHOP chemotherapy. CONCLUSION: IVL should be
included in the differential diagnosis of atypical case of presumed myelitis. An
early diagnosis and chemotherapy is crucial for improving the patient's outcome.
When obtaining a diagnosis based on tissues other than skin is difficult, a
random skin biopsy should be considered in patients with suspected IVL.
PMID- 26421217
TI - Treatment of giant congenital cysts of the midline in adults: Report of two cases
and review of the literature.
AB - BACKGROUND: Giant cysts of the midline, not associated to a tumor, are
exceptional finding in the brain of adults. Here we present two cases of
symptomatic giant cerebral cysts of the midline occurred in an elderly and in a
young adult patients both treated with mini-invasive unilateral neuroendoscopic
procedure. In the recent literature (since 1999) similar cases have not been
reported. Beside the clinical report, review of literature and major anatomical
features of the region are described. CASE DESCRIPTION: These two adults (82 and
41 years old respectively) had a slow progressive development of headache, gait
disturbances, memory impairment and urinary incontinence. Magnetic resonance
imaging showed giant cyst of the midline and hydrocephalus. Surgery with the
endoscopic procedure, through a right frontal burr hole, was followed by clinical
and radiological improvement. CONCLUSION: Giant cerebral cysts of the midline in
adults can be successfully treated through a neuroendoscopic monolateral approach
that comprehends multiple openings, diffuse coagulation of the capsule, and
careful releasing of capsule-ependyma adherences. Knowledge of major anatomical
and developmental details of the septal region is necessary to avoid complication
in a mini-invasive surgical procedure.
PMID- 26421218
TI - Cavernous hemangioma of the dura mater mimicking meningioma.
AB - BACKGROUND: Cavernomas are benign lesions that most commonly occur intra
parenchymally, but occasionally they have been described as arising from the dura
mater. Extra-axial cavernous angiomas (or hemangiomas) account for 0.4-2% of all
intracranial vascular malformations, and they usually occur in the middle cranial
fossa, associated with the cavernous sinus. Other possible localizations (e.g.
tentorium, convexity, anterior cranial fossa, cerebellopontine angle, Meckel's
cave, sella turcica and internal auditory meatus) are rare, and they account only
for 0.2-0.5%. CASE DESCRIPTION: We report a case of a 30-year-old female
presenting with a 2 years history of headache unresponsive to drug therapy. The
magnetic resonance imaging showed a dural-based lesion in the left frontal
region; the lesion size was: 1.5 cm * 3.5 cm. The appearance suggested a
convexity meningioma. A left frontal craniotomy was performed, and the
histopathological diagnosis deposed for a cavernous hemangioma of the dura mater.
The follow-up at 1-year was good without any neurologic deficit. CONCLUSIONS:
Dural-based cavernous hemangiomas of the convexity are uncommon lesions. Up to
now, only 13 cases have been described in the literature. The authors have
discussed clinical aspects, radiological features, surgical treatment, and
operative findings.
PMID- 26421219
TI - We Don't Know What We Don't Know About Adolescent and Young Adult Patients with
Familial Adenomatous Polyposis-Related Colorectal Cancer.
PMID- 26421221
TI - Exercise and Fatigue in Adolescent and Young Adult Survivors of Hodgkin Lymphoma:
A Report from the Children's Oncology Group.
AB - Fatigue is a significant problem for adolescent and young adult (AYA) Hodgkin
lymphoma (HL) survivors. The relationship between exercise and fatigue is
complex. This study explored the trajectory of and the relationship between
exercise and fatigue over 36 months post-therapy in a cohort of 103 AYA-aged HL
survivors treated on Children's Oncology Group (COG) study AHOD0031. Descriptive
statistics and generalized estimating equations were used in this secondary data
analysis. Exercise and fatigue improved over time but were unrelated; amount of
exercise at end of therapy predicted amount of exercise at 12 (p = 0.02) and 36
(p = 0.0008) months post-therapy.
PMID- 26421220
TI - Best Practices in Adolescent and Young Adult Patients with Acute Lymphoblastic
Leukemia: A Focus on Asparaginase.
AB - The inclusion of asparaginase in chemotherapy regimens to treat acute
lymphoblastic leukemia (ALL) has had a positive impact on survival in pediatric
patients. Historically, asparaginase has been excluded from most treatment
protocols for adolescent and young adult (AYA) patients because of perceived
toxicity in this population, and this is believed to have contributed to poorer
outcomes in these patients. However, retrospective analyses over the past 12
years have shown that 2-, 5-, and 7-year overall survival of AYA patients is
significantly improved with pediatric versus adult protocols. The addition of
asparaginase to adult protocols yielded high rates of first remission and
improved survival. However, long-term survival remains lower compared with what
has been seen in pediatrics. The notion that asparaginase is poorly tolerated by
AYA patients has been challenged in multiple studies. In some, but not all,
studies, the incidences of hepatic and pancreatic toxicities were higher in AYA
patients, whereas the rates of hypersensitivity reactions did not appear to
differ with age. There is an increased risk of venous thromboembolic events, and
management with anti-coagulation therapy is recommended. Overall, the risk of
therapy-related mortality is low. Together, this suggests that high-intensity
pediatric protocols offer an effective and tolerable approach to treating ALL in
the AYA population.
PMID- 26421223
TI - Novel Nut and Bolt Task Quantifies Motor Deficits in Premanifest and Manifest
Huntington's Disease.
AB - BACKGROUND: We investigated the use of a simple novel nut and bolt task in
premanifest and manifest Huntington's disease (HD) patients to detect and
quantify motor impairments at all stages of the disease. METHODS: Premanifest HD
(n=24), manifest HD (n=27) and control (n=32) participants were asked to screw a
nut onto a bolt in one direction, using three different sized bolts with their
left and right hand in turn. RESULTS: We identified some impairments at all
stages of HD and in the premanifest individuals, deficits in the non-dominant
hand correlated with disease burden scores. CONCLUSION: This simple, cheap motor
task was able to detect motor impairments in both premanifest and manifest HD and
as such might be a useful quantifiable measure of motor function for use in
clinical studies.
PMID- 26421222
TI - Who Treats Adolescents and Young Adults with Cancer? A Report from the AYA HOPE
Study.
AB - PURPOSE: Physicians play a critical role in delivering effective treatment and
enabling successful transition to survivorship among adolescent and young adult
(AYA) cancer patients. However, with no AYA cancer medical specialty, information
on where and by whom AYAs with cancer are treated is limited. METHODS: Using the
National Cancer Institute's population-based AYA HOPE Study, 464 AYAs aged 15-39
at diagnosis treated by 903 physicians were identified. Differences in physician
and hospital characteristics were examined by age at diagnosis and cancer type
(germ cell cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, acute lymphocytic
leukemia [ALL], and sarcoma) using chi-square tests. RESULTS: Treating physicians
were predominately 51-64 years old, male, United States-trained in non-pediatric
specialties, and in group practices within large metropolitan areas. Older
patients were less often treated by pediatric physicians (p < 0.01) and more
likely to be treated by United States-trained physicians without
research/teaching responsibilities and in hospitals without residency programs (p
< 0.05). The majority of the few pediatricians (n = 44) treated ALL patients.
Physicians with research/teaching responsibilities and those based in medical
schools were more likely to treat patients with ALL and sarcoma compared with
other cancer types (p < 0.01). Of HL patients, 73% were treated at a cancer
center compared with 56% of patients with germ cell cancer (p < 0.01), while ALL
(85%) and sarcoma (87%) patients were more likely to be treated in hospitals with
residency programs (p < 0.01). CONCLUSIONS: Most AYAs with cancer were treated by
non-pediatric physicians in community settings, although physician
characteristics varied significantly by patient cancer type and age at diagnosis.
PMID- 26421224
TI - Acousto-plasmofluidics: Acoustic modulation of surface plasmon resonance in
microfluidic systems.
AB - We acoustically modulated the localized surface plasmon resonances (LSPRs) of
metal nanostructures integrated within microfluidic systems. An acoustically
driven micromixing device based on bubble microstreaming quickly and
homogeneously mixes multiple laminar flows of different refractive indices. The
altered refractive index of the mixed fluids enables rapid modulation of the
LSPRs of gold nanodisk arrays embedded within the microfluidic channel. The
device features fast response for dynamic operation, and the refractive index
within the channel is tailorable. With these unique features, our "acousto
plasmofluidic" device can be useful in applications such as optical switches,
modulators, filters, biosensors, and lab-on-a-chip systems.
PMID- 26421225
TI - The Wellbeing of the Workforce-In Healthcare and Beyond.
PMID- 26421226
TI - Resilience, Empathy, and Wellbeing in the Health Professions: An Educational
Imperative.
PMID- 26421227
TI - In Name and Concept: The Global Uptake of the Movement for Integrative Medicine
and Health.
PMID- 26421228
TI - Caring for People Behind the Numbers: Measurement and Accountability for Health.
PMID- 26421229
TI - Weaving Elders of the Andes.
PMID- 26421230
TI - Prioritizing Clinician Wellbeing: The University of Virginia's Compassionate Care
Initiative.
AB - BACKGROUND: Working in healthcare is increasingly challenging for nurses,
physicians, and other health professionals. Ongoing high stress takes a toll on
clinicians and interferes with the quality of their patient care. Fostering
clinician wellbeing needs to be a priority; if not, the human and financial
consequences are significant. OBJECTIVE: To describe the University of Virginia
(UVA) School of Nursing's Compassionate Care Initiative (CCI) as an example of an
organizational case study that is engaged in multipronged efforts to cultivate a
resilient healthcare workforce committed to high-quality, compassionate,
relationship-based care. METHODS: This case report describes the development,
implementation, and evaluation of the CCI at UVA. Various elements of the program
are reviewed, which include harnessing talents and interests of the larger
institution in the establishment of Compassionate Care Ambassadors, outreach to
the community, innovative student-specific educational activities, and a national
media program. CONCLUSION: The UVA CCI is a successful model of an organizational
effort to promote clinician wellbeing and resilience. Aspects from this program
can be adapted to other organizations that are committed to addressing this
critical issue in US healthcare today.
PMID- 26421231
TI - Preventing Chronic Pain: A Human Systems Approach-Results From a Massive Open
Online Course.
AB - Chronic pain conditions are the top reason patients seek care, the most common
reason for disability and addiction, and the biggest driver of healthcare costs;
their treatment costs more than cancer, heart disease, dementia, and diabetes
care. The personal impact in terms of suffering, disability, depression, suicide,
and other problems is incalculable. There has been much effort to prevent many
medical and dental conditions, but little effort has been directed toward
preventing chronic pain. To address this deficit, a massive open online course
(MOOC) was developed for students and healthcare professionals. "Preventing
Chronic Pain: A Human Systems Approach" was offered by the University of
Minnesota through the online platform Coursera. The first offering of this free
open course was in the spring of 2014 and had 23 650 participants; 53% were
patients or consumers interested in pain. This article describes the course
concepts in preventing chronic pain, the analytic data from course participants,
and postcourse evaluation forms.
PMID- 26421232
TI - Interprofessional Competencies in Integrative Primary Healthcare.
AB - In October 2014, the National Center for Integrative Primary Healthcare (NCIPH)
was launched as a collaboration between the University of Arizona Center for
Integrative Medicine and the Academic Consortium for Integrative Health and
Medicine and supported by a grant from the Health Resources and Services
Administration. A primary goal of the NCIPH is to develop a core set of
integrative healthcare (IH) competencies and educational programs that will span
the interprofessional primary care training and practice spectra and ultimately
become a required part of primary care education. This article reports on the
first phase of the NCIPH effort, which focused on the development of a shared set
of competencies in IH for primary care disciplines. The process of development,
refinement, and adoption of 10 "meta-competencies" through a collaborative
process involving a diverse interprofessional team is described. Team members
represent nursing, the primary care medicine professions, pharmacy, public
health, acupuncture, naturopathy, chiropractic, nutrition, and behavioral
medicine. Examples of the discipline-specific sub-competencies being developed
within each of the participating professions are provided, along with initial
results of an assessment of potential barriers and facilitators of adoption
within each discipline. The competencies presented here will form the basis of a
45-hour online curriculum produced by the NCIPH for use in primary care training
programs that will be piloted in a wide range of programs in early 2016 and then
revised for wider use over the following year.
PMID- 26421233
TI - Aligning Theory and Design: The Development of an Online Learning Intervention to
Teach Evidence-based Practice for Maximal Reach.
AB - BACKGROUND: Online educational interventions to teach evidence-based practice
(EBP) are a promising mechanism for overcoming some of the barriers to
incorporating research into practice. However, attention must be paid to aligning
strategies with adult learning theories to achieve optimal outcomes. METHODS: We
describe the development of a series of short self-study modules, each covering a
small set of learning objectives. Our approach, informed by design-based research
(DBR), involved 6 phases: analysis, design, design evaluation, redesign,
development/implementation, and evaluation. Participants were faculty and
students in 3 health programs at a complementary and integrative educational
institution. RESULTS: We chose a reusable learning object approach that allowed
us to apply 4 main learning theories: events of instruction, cognitive load, dual
processing, and ARCS (attention, relevance, confidence, satisfaction). A
formative design evaluation suggested that the identified theories and
instructional approaches were likely to facilitate learning and motivation.
Summative evaluation was based on a student survey (N=116) that addressed how
these theories supported learning. Results suggest that, overall, the selected
theories helped students learn. CONCLUSION: The DBR approach allowed us to
evaluate the specific intervention and theories for general applicability. This
process also helped us define and document the intervention at a level of detail
that covers almost all the proposed Guideline for Reporting Evidence-based
practice Educational intervention and Teaching (GREET) items. This thorough
description will facilitate the interpretation of future research and
implementation of the intervention. Our approach can also serve as a model for
others considering online EBP intervention development.
PMID- 26421236
TI - Scanning the Global Literature.
PMID- 26421234
TI - Advancing One Health Policy and Implementation Through the Concept of One
Medicine One Science.
AB - Numerous interspecies disease transmission events, Ebola virus being a recent and
cogent example, highlight the complex interactions between human, animal, and
environmental health and the importance of addressing medicine and health in a
comprehensive scientific manner. The diversity of information gained from the
natural, social, behavioral, and systems sciences is critical to developing and
sustainably promoting integrated health approaches that can be implemented at the
local, national, and international levels to meet grand challenges. The Concept
of One Medicine One Science (COMOS) as outlined herein describes the interplay
between scientific knowledge that underpins health and medicine and efforts
toward stabilizing local systems using 2 linked case studies: the food system and
emerging infectious disease. Forums such as the International Conference of One
Medicine One Science (iCOMOS), where science and policy can be debated together,
missing pieces identified, and science-based collaborations formed among
industry, governmental, and nongovernmental policy makers and funders, is an
essential step in addressing global health. The expertise of multiple disciplines
and research foci to support policy development is critical to the implementation
of one health and the successful achievement of global health security goals.
PMID- 26421235
TI - Immediate Effect of Therapeutic Massage on Pain Sensation and Unpleasantness: A
Consecutive Case Series.
AB - BACKGROUND: Musculoskeletal pain is a common condition that poses a significant
burden to its sufferers and costs the US economy billions of dollars each year in
lost productivity. Individuals complaining of musculoskeletal pain make up a
large proportion of clients treated by massage therapists in community practices,
yet few studies have examined the immediate effect of therapeutic massage on this
type of pain in the practice setting. PURPOSE: To assess the immediate effect of
therapeutic massage on musculoskeletal pain sensation and unpleasantness in a
community setting. SETTING: Solo private practice in central Virginia, United
States. PARTICIPANTS: One hundred sixteen first-time clients who complained of
musculoskeletal pain as a presenting symptom. RESEARCH DESIGN: Prospective,
consecutive practice-based case series. INTERVENTION: A single 60-minute session
of individualized therapeutic massage; techniques used included Swedish massage
employing effleurage, petrissage, and friction,;deep tissue; myofascial;
positional release; passive and resisted joint mobilization; and biofield
modalities. MAIN OUTCOME MEASURES: Visual Analog Scales for pain sensation and
unpleasantness. RESULTS: Both pain sensation and unpleasantness were
significantly reduced by a single session of therapeutic massage. Mean pain
sensation decreased from 3.76 (SD=1.87) prior to massage to .89 (SD=1.35)
following massage, with t=18.87, P<.001. Mean pain unpleasantness decreased from
5.21 (SD=2.48) prior to massage to .64 (SD=1.23) following massage, with t
=20.45, P<.001. Effect sizes were 1.76 and 1.90, respectively. CONCLUSIONS: In
this case series, therapeutic massage appeared to be an effective intervention
for common musculoskeletal pain that influenced both the physical and affective
dimension of the pain experience. Although care was taken to reduce potential
bias through limiting eligibility to first time clients and use of a standardized
script, practice-based case series have inherent limitations. Issues in
conducting practice-based research by massage therapists and recommendations for
future research are discussed.
PMID- 26421237
TI - Modeling historical tuberculosis epidemics among Canadian First Nations: effects
of malnutrition and genetic variation.
AB - Late 19th century epidemics of tuberculosis (TB) in Western Canadian First
Nations resulted in peak TB mortality rates more than six times the highest rates
recorded in Europe. Using a mathematical modeling approach and historical TB
mortality time series, we investigate potential causes of high TB mortality and
rapid epidemic decline in First Nations from 1885 to 1940. We explore two
potential causes of dramatic epidemic dynamics observed in this setting: first,
we explore effects of famine prior to 1900 on both TB and population dynamics.
Malnutrition is recognized as an individual-level risk factor for TB progression
and mortality; its population-level effects on TB epidemics have not been
explored previously. Second, we explore effects of heterogeneity in
susceptibility to TB in two ways: modeling heterogeneity in susceptibility to
infection, and heterogeneity in risk of developing disease once infected. Our
results indicate that models lacking famine-related changes in TB parameters or
heterogeneity result in an implausibly poor fit to both the TB mortality time
series and census data; the inclusion of these features allows for the
characteristic decline and rise in population observed in First Nations during
this time period and confers improved fits to TB mortality data.
PMID- 26421238
TI - Prediction of junior faculty success in biomedical research: comparison of
metrics and effects of mentoring programs.
AB - Measuring and predicting the success of junior faculty is of considerable
interest to faculty, academic institutions, funding agencies and faculty
development and mentoring programs. Various metrics have been proposed to
evaluate and predict research success and impact, such as the h-index, and
modifications of this index, but they have not been evaluated and validated side
by-side in a rigorous empirical study. Our study provides a retrospective
analysis of how well bibliographic metrics and formulas (numbers of total, first-
and co-authored papers in the PubMed database, numbers of papers in high-impact
journals) would have predicted the success of biomedical investigators (n = 40)
affiliated with the University of Nevada, Reno, prior to, and after completion of
significant mentoring and research support (through funded Centers of Biomedical
Research Excellence, COBREs), or lack thereof (unfunded COBREs), in 2000-2014.
The h-index and similar indices had little prognostic value. Publishing as mid-
or even first author in only one high-impact journal was poorly correlated with
future success. Remarkably, junior investigators with >6 first-author papers
within 10 years were significantly (p < 0.0001) more likely (93%) to succeed than
those with <=6 first-author papers (4%), regardless of the journal's impact
factor. The benefit of COBRE-support increased the success rate of junior faculty
approximately 3-fold, from 15% to 47%. Our work defines a previously neglected
set of metrics that predicted the success of junior faculty with high fidelity
thus defining the pool of faculty that will benefit the most from faculty
development programs such as COBREs.
PMID- 26421239
TI - The influence of arbuscular mycorrhizal fungi inoculation on yam (Dioscorea spp.)
tuber weights and secondary metabolite content.
AB - Arbuscular mycorrhizal fungi (AMF) are widely distributed in nature. They live in
the roots of higher plants, in a symbiotic relationship. In this study, five
commercial species of yams (Dioscorea spp.) were inoculated with six species of
AMF, Glomus clarum, G. etunicatum, G. fasciculatum, Gigaspora sp., G. mosseae,
and Acaulospora sp., in field cultivation conditions to investigate the influence
of AMF inoculation on tuber weights and secondary metabolite content in yam
tubers. The results showed that mycorrhizae formation rates ranged from 63.33% to
90%. G. etunicatum inoculation treatment increased the tube weights of the five
species of yam tubers by 39%, 35%, 20%, 56%, and 40% for Tainung 1, Tainung 2,
Ercih, Zihyuxieshu, and Tainung 5, respectively. The content of secondary
metabolites, such as polyphenols, flavonoids, and anthocyanin, was significantly
increased by the AMF treatment in tuber flesh and peel of all the tested yam
species. Specifically, the maximums exchange of secondary metabolite contents
increased to 40%, 42%, and 106% for polyphenols, flavonoids, and anthocyanin,
respectively, in the tuber fresh. This study revealed that different species of
yam had varying degrees of affinity with various AMF species; selecting effective
AMF species is necessary to facilitate yam growth and improve the quality and
quantity of yam tubers.
PMID- 26421240
TI - Looking for a generic inhibitor of amyloid-like fibril formation among flavone
derivatives.
AB - A range of diseases is associated with amyloid fibril formation. Despite
different proteins being responsible for each disease, all of them share similar
features including beta-sheet-rich secondary structure and fibril-like protein
aggregates. A number of proteins can form amyloid-like fibrils in vitro,
resembling structural features of disease-related amyloids. Given these generic
structural properties of amyloid and amyloid-like fibrils, generic inhibitors of
fibril formation would be of interest for treatment of amyloid diseases.
Recently, we identified five outstanding inhibitors of insulin amyloid-like
fibril formation among the pool of 265 commercially available flavone
derivatives. Here we report testing of these five compounds and of epi
gallocatechine-3-gallate (EGCG) on aggregation of alpha-synuclein and beta
amyloid. We used a Thioflavin T (ThT) fluorescence assay, relying on halftimes of
aggregation as the measure of inhibition. This method avoids large numbers of
false positive results. Our data indicate that four of the five flavones and EGCG
inhibit alpha-synuclein aggregation in a concentration-dependent manner. However
none of these derivatives were able to increase halftimes of aggregation of beta
amyloid.
PMID- 26421241
TI - The impact of Docker containers on the performance of genomic pipelines.
AB - Genomic pipelines consist of several pieces of third party software and, because
of their experimental nature, frequent changes and updates are commonly necessary
thus raising serious deployment and reproducibility issues. Docker containers are
emerging as a possible solution for many of these problems, as they allow the
packaging of pipelines in an isolated and self-contained manner. This makes it
easy to distribute and execute pipelines in a portable manner across a wide range
of computing platforms. Thus, the question that arises is to what extent the use
of Docker containers might affect the performance of these pipelines. Here we
address this question and conclude that Docker containers have only a minor
impact on the performance of common genomic pipelines, which is negligible when
the executed jobs are long in terms of computational time.
PMID- 26421242
TI - Temporal stability of an endemic Mexican treefrog.
AB - The demographic characteristics of an amphibian population fluctuate
independently over time, mainly in response to the temporal variation of
environmental factors, especially precipitation and temperature. These temporal
fluctuations may contribute to the size of an amphibian population and could be
used to determine the current conservation status of a species. During a five
year (2004-2008) period, we studied the relative abundance, sex ratio, and age
sex structure of a population of metamorphosed individuals of the endemic
treefrog Hyla eximia in Central Mexico. We also studied the species' relationship
with climatic variables such as temperature and precipitation. We found an
interannual constant abundance during the study period. However, interannual
differences were observed in the population structure by age-sex category (males,
females, or juveniles), with decreased abundance of males and juveniles during
the rainy months (August-November). The annual abundance of H. eximia was
positively correlated with rainfall, but negatively with monthly temperature. We
found the sex ratio was male-biased (2:1), except for year 2008. Also,
differences in snout-vent length (SVL) were found between years, suggesting
changes in recruitment of new individuals. We conclude that variations in
abundance, and frequencies by age-sex category, of H. eximia are related to
seasonal variations in temperature and precipitation characteristics of temperate
zones. However, this temporal stability may suggest that anurans have an unusual
capacity to persist even in the face of human-induced habitat change.
PMID- 26421243
TI - Pair formation, home range, and spatial variation in density, size and social
status in blotched foxface Siganus unimaculatus on an Okinawan coral reef.
AB - The present study examined pair formation, spatial pattern of home range and
spatial variation in density, size and social status of blotched foxface Siganus
unimaculatus (family Siganidae) on an Okinawan coral reef. Of 32 pairs sampled
for sexing, 31 (96.9%) were heterosexual and showed size-assortative pairing.
Developed ovaries were found in April and July, whereas oocytes were immature in
August, September and February. Heterosexual pairing was found in both
reproductive and non-reproductive periods. Home range size tended to be
positively related to fork length (FL). The degree of home range overlap for same
size class pairs was smaller than that for different size class pairs. The
intraspecific behavior when two pairs approached each other was categorized as
'attack,' 'agonistic display' and 'no interactions,' and the frequency of
agonistic behaviors ("attack" or "agonistic display") was significantly greater
than "no interactions." Underwater observations at a seagrass bed, a rocky reef
flat and a sheltered reef slope revealed that the mean FL was significantly
smaller at the sheltered reef slope (4-13 cm) than at the rocky reef flat (>13
cm). No individuals were found in the seagrass bed. Most individuals less than 6
cm FL were solitary, whereas most individuals over 7 cm FL were paired. Density
was significantly greater on the sheltered reef slope than on the rocky reef
flat.
PMID- 26421244
TI - Acute effects of anterior thigh foam rolling on hip angle, knee angle, and rectus
femoris length in the modified Thomas test.
AB - Background. Foam rolling has been shown to acutely increase range of motion (ROM)
during knee flexion and hip flexion with the experimenter applying an external
force, yet no study to date has measured hip extensibility as a result of foam
rolling with controlled knee flexion and hip extension moments. The purpose of
this study was to investigate the acute effects of foam rolling on hip extension,
knee flexion, and rectus femoris length during the modified Thomas test. Methods.
Twenty-three healthy participants (male = 7; female = 16; age = 22 +/- 3.3 years;
height = 170 +/- 9.18 cm; mass = 67.7 +/- 14.9 kg) performed two, one-minute
bouts of foam rolling applied to the anterior thigh. Hip extension and knee
flexion were measured via motion capture before and after the foam rolling
intervention, from which rectus femoris length was calculated. Results. Although
the increase in hip extension (change = +1.86 degrees (+0.11, +3.61); z(22) =
2.08; p = 0.0372; Pearson's r = 0.43 (0.02, 0.72)) was not due to chance alone,
it cannot be said that the observed changes in knee flexion (change = -1.39
degrees (-5.53, +2.75); t(22) = -0.70; p = 0.4933; Cohen's d = - 0.15 (-0.58,
0.29)) or rectus femoris length (change = -0.005 (-0.013, +0.003); t(22) = -1.30;
p = 0.2070; Cohen's d = - 0.27 (-0.70, 0.16)) were not due to chance alone.
Conclusions. Although a small change in hip extension was observed, no changes in
knee flexion or rectus femoris length were observed. From these data, it appears
unlikely that foam rolling applied to the anterior thigh will improve passive hip
extension and knee flexion ROM, especially if performed in combination with a
dynamic stretching protocol.
PMID- 26421245
TI - An examination of disparities in cancer incidence in Texas using Bayesian random
coefficient models.
AB - Disparities in cancer risk exist between ethnic groups in the United States.
These disparities often result from differential access to healthcare,
differences in socioeconomic status and differential exposure to carcinogens.
This study uses cancer incidence data from the population based Texas Cancer
Registry to investigate the disparities in digestive and respiratory cancers from
2000 to 2008. A Bayesian hierarchical regression approach is used. All models are
fit using the INLA method of Bayesian model estimation. Specifically, a spatially
varying coefficient model of the disparity between Hispanic and Non-Hispanic
incidence is used. Results suggest that a spatio-temporal heterogeneity model
best accounts for the observed Hispanic disparity in cancer risk. Overall, there
is a significant disadvantage for the Hispanic population of Texas with respect
to both of these cancers, and this disparity varies significantly over space. The
greatest disparities between Hispanics and Non-Hispanics in digestive and
respiratory cancers occur in eastern Texas, with patterns emerging as early as
2000 and continuing until 2008.
PMID- 26421246
TI - Laparoscopic Gastric Plication: An Emerging Bariatric Procedure with High
Surgical Revision Rate.
AB - Introduction: Laparoscopic gastric plication (LGCP) reduces gastric volume
without resecting or implanting a foreign body. Although still considered
investigational, it could be appropriate for young patients with a low body mass
index (BMI) and for those unwilling to undergo sleeve gastrectomy, gastric
banding, or bypass. Objectives: The aim of this study was to assess the mid-term
results (2 years) of LGCP in terms of safety and efficacy. Methods: A total of 56
obese patients (47 female; mean age=30.5+/-11.7 years; mean BMI=40.31+/-4.7
kg/m2) were candidates for LGCP from January 2011 to October 2013. Early and late
complications, BMI, and excess BMI loss (EBL) were prospectively recorded at 3,
6, 9, 12, 18, and 24 months follow-up. Results: Mean operative time was 72.4+/
15.6 minutes. No conversion was required. Mean hospital stay was 3 days. Mean
%EBL was 34.3+/-18.40%, 40.1+/-24.5%, 47.4+/-30.2%, 46.5+/-34.6%, 47.8+/-43.2%,
and 55.3+/-53.6% at 3, 6, 9, 12, 18, and 24 months, respectively. The overall
complication rate was 32.14%. Perioperative mortality was zero. Surgical revision
was needed in 30 patients: 12 for unsatisfactory weight loss and 18 for gastric
prolapse (one acute within 30 days), respectively. Conclusion: LGCP showed high
complication rates requiring surgical revision.
PMID- 26421247
TI - Medication Use Among Patients Prior to Bariatric Surgery.
AB - Purpose: The aims of this study were to describe the most common medications
reported by candidates for weight loss surgery and to consider the potential
implications for patient care. Methods: A secondary data analysis of data from
bariatric surgery patients enrolled in a randomized, controlled trial. At study
entry, participants recorded their use of prescription medications they had taken
in the previous 90 days. The Anatomical Therapeutic Chemical (ATC)/Defined Daily
Dose (DDD) Index 2014 was used to classify medications. Results: Participants
(n=265) were 85.7% female and 83.0% white. Mean body mass index was 47.9+/-6.5
kg/m2, and age was 45.1+/-11 years. The average number of medications was 4.4+/
4.1, and the median was 3. The top three anatomical main groups were the
cardiovascular system, alimentary tract and metabolism, and nervous system
(28.2%, 21.6%, and 21.3% of all medications, respectively). The top therapeutic
subgroups were drugs used in diabetes, psychoanaleptics, and agents acting on the
renin-angiotensin system (12%, 11.3%, and 8.2% of all medications, respectively).
Conclusions: Candidates for weight loss surgery report taking medications
associated with obesity-related comorbidities such as diabetes, depression, and
hypertension. Although many may be able to eliminate these medications, others
will require close monitoring and dosage adjustment after surgery.
PMID- 26421248
TI - Does Preoperative Weight Change Predict Postoperative Weight Loss After
Laparoscopic Sleeve Gastrectomy?
AB - Background: Some institutions and insurance companies mandate a preoperative
weight loss regimen prior to bariatric surgery. Previous studies suggest little
to no correlation between preoperative and postoperative weight loss for
laparoscopic Roux-en-Y gastric bypass (RNYGB). This study examined the impact of
preoperative weight change for patients undergoing laparoscopic sleeve
gastrectomy (LSG). Materials and Methods: A retrospective analysis was performed
on patients undergoing LSG at the authors' institution from 2010 to 2012.
Patients were grouped based on preoperative weight gain or loss. The correlation
between preoperative BMI change and postoperative BMI change was studied, as well
as length of surgery. Results: Of 141 patients with 1-year follow-up, 72 lost,
six maintained, and 64 gained weight preoperatively. Percentage of excess BMI
loss at 1 year was not statistically different between those who lost weight and
those who gained weight. Percent change in BMI from initial visit to surgery does
not correlate with change in BMI at 1 year postoperatively or with length of
surgery. Conclusions: Preoperative weight loss is not a reliable predictor of
postoperative weight loss or shorter operative time after LSG. Potential patients
who otherwise meet indications for LSG should not be denied based on inability to
lose weight.
PMID- 26421249
TI - Characterization of 14 microsatellite markers for Silene acaulis
(Caryophyllaceae)(1).
AB - PREMISE OF THE STUDY: Fifty candidate microsatellite markers, generated using 454
shotgun sequencing, were tested for the widespread arctic/alpine herb Silene
acaulis (Caryophyllaceae). METHODS AND RESULTS: Fourteen out of 50 markers
resulted in polymorphic products with profiles that enabled interpretation. The
numbers of alleles per locus ranged from two to six, and the expected
heterozygosity per locus ranged from 0.06 to 0.68. Analysis of F0 and F1 samples
proved that one allele was always inherited maternally. Four multiplex mixes have
been developed. CONCLUSIONS: Microsatellite markers for this species will be a
valuable tool to study detailed small-scale genetic patterns in an arctic/alpine
herb and to relate them to demographic parameters.
PMID- 26421250
TI - Development of 23 novel polymorphic EST-SSR markers for the endangered relict
conifer Metasequoia glyptostroboides.
AB - PREMISE OF THE STUDY: Metasequoia glyptostroboides is an endangered relict
conifer species endemic to China. In this study, expressed sequence tag-simple
sequence repeat (EST-SSR) markers were developed using transcriptome mining for
future genetic and functional studies. METHODS AND RESULTS: We collected 97,565
unigene sequences generated by 454 pyrosequencing. A bioinformatics analysis
identified 2087 unique and putative microsatellites, from which 96 novel
microsatellite markers were developed. Fifty-three of the 96 primer sets
successfully amplified clear fragments of the expected sizes; 23 of those loci
were polymorphic. The number of alleles per locus ranged from two to eight, with
an average of three, and the observed and expected heterozygosity values ranged
from 0 to 1.0 and 0.117 to 0.813, respectively. CONCLUSIONS: These microsatellite
loci will enrich the genetic resources to develop functional studies and
conservation strategies for this endangered relict species.
PMID- 26421251
TI - Bioinformatic identification and expression analysis of Nelumbo nucifera microRNA
and their targets.
AB - PREMISE OF THE STUDY: Sacred lotus (Nelumbo nucifera) is a perennial aquatic
herbaceous plant of ecological, ornamental, and economic importance. MicroRNAs
(miRNAs) play an important role in plant development. However, reports of miRNAs
and their role in sacred lotus have been limited. METHODS: Using the homology
search of known miRNAs with genome and transcriptome contig sequences, we
employed a pipeline to identify miRNAs in N. nucifera. We also predicted the
targets of these miRNAs. RESULTS: We found 106 conserved miRNAs in N. nucifera,
and 456 of their miRNA targets were annotated. Quantitative real-time PCR (qRT
PCR) analysis revealed the different expression levels of the 10 selected
conserved miRNAs in tissues of young leaves, stems, and flowers of N. nucifera.
Negative correlation of expression level between five miRNAs and their target
genes was also revealed. DISCUSSION: Combining bioinformatics and experiment
analysis, we identified the miRNAs in N. nucifera. The results can be used as a
workbench for further investigation of the roles of miRNAs in N. nucifera.
PMID- 26421252
TI - Development and characterization of microsatellite loci in the pantropical fern
Hypolepis punctata (Dennstaedtiaceae).
AB - PREMISE OF THE STUDY: Microsatellite loci were isolated in Hypolepis punctata
(Dennstaedtiaceae) to further study the reproductive ecology of this species.
METHODS AND RESULTS: We developed 16 microsatellite loci from one sample of H.
punctata using an enriched genomic library. These loci were characterized in 28
individuals. The number of alleles per locus ranged from two to 10, and the
expected heterozygosity ranged from 0.036 to 0.845. CONCLUSIONS: The results
indicate that the microsatellite markers can facilitate further studies on
inferring the phylogeography and population genetics of H. punctata and related
species.
PMID- 26421253
TI - Chloroplast microsatellite markers for Artocarpus (Moraceae) developed from
transcriptome sequences.
AB - PREMISE OF THE STUDY: Chloroplast microsatellite loci were characterized from
transcriptomes of Artocarpus altilis (breadfruit) and A. camansi (breadnut). They
were tested in A. odoratissimus (terap) and A. altilis and evaluated in silico
for two congeners. METHODS AND RESULTS: Fifteen simple sequence repeats (SSRs)
were identified in chloroplast sequences from four Artocarpus transcriptome
assemblies. The markers were evaluated using capillary electrophoresis in A.
odoratissimus (105 accessions) and A. altilis (73). They were also evaluated in
silico in A. altilis (10), A. camansi (6), and A. altilis * A. mariannensis (7)
transcriptomes. All loci were polymorphic in at least one species, with all 15
polymorphic in A. camansi. Per species, average alleles per locus ranged between
2.2 and 2.5. Three loci had evidence of fragment-length homoplasy. CONCLUSIONS:
These markers will complement existing nuclear markers by enabling confident
identification of maternal and clone lines, which are often important in
vegetatively propagated crops such as breadfruit.
PMID- 26421254
TI - Development and characterization of 11 microsatellite primers for the sedge
Trichophorum planifolium (Cyperaceae).
AB - PREMISE OF THE STUDY: Microsatellite loci were developed for Trichophorum
planifolium (Cyperaceae), an endangered woodland sedge protected under federal
and provincial legislation in Canada, to explore patterns of population genetic
diversity and differentiation in the species. METHODS AND RESULTS: Sixty-three
primer pairs were evaluated for amplification consistency and screened for
polymorphisms in 96 samples collected from 12 populations of T. planifolium
distributed through the range of the species. Of these, 11 loci were shown to be
polymorphic, displaying two to six alleles. Mean observed heterozygosity across
loci ranged from 0.00 to 0.06 among populations tested. CONCLUSIONS: The results
suggest that the 11 primer pairs developed in this study will be useful for
future studies of broad-scale genetic variation in T. planifolium and in guiding
management protocols for the species in Canada.
PMID- 26421255
TI - Development of microsatellite loci for the endangered seagrass Zostera japonica
(Zosteraceae).
AB - PREMISE OF THE STUDY: New microsatellite markers were developed for the Asian
endangered seagrass Zostera japonica (Zosteraceae) to assess genetic diversity
and population structure of this species. In China, Z. japonica populations have
drastically decreased since the 1970s. METHODS AND RESULTS: A total of 12
polymorphic tetranucleotide microsatellite loci were isolated and characterized
in Z. japonica. The number of alleles per locus ranged from one to 11. The
expected and observed heterozygosity ranged from 0 to 0.772 and from 0 to 1.000,
respectively. CONCLUSIONS: The new microsatellites will be useful in evaluating
clonality and population structure of Z. japonica and aiding in conservation and
management of the endangered seagrass in Asia.
PMID- 26421257
TI - Correction: Hypersexuality Addiction and Withdrawal: Phenomenology, Neurogenetics
and Epigenetics.
AB - [This corrects the article DOI: 10.7759/cureus.290.].
PMID- 26421256
TI - Digitization workflows for flat sheets and packets of plants, algae, and fungi.
AB - Effective workflows are essential components in the digitization of biodiversity
specimen collections. To date, no comprehensive, community-vetted workflows have
been published for digitizing flat sheets and packets of plants, algae, and
fungi, even though latest estimates suggest that only 33% of herbarium specimens
have been digitally transcribed, 54% of herbaria use a specimen database, and 24%
are imaging specimens. In 2012, iDigBio, the U.S. National Science Foundation's
(NSF) coordinating center and national resource for the digitization of public,
nonfederal U.S. collections, launched several working groups to address this
deficiency. Here, we report the development of 14 workflow modules with 7-36
tasks each. These workflows represent the combined work of approximately 35
curators, directors, and collections managers representing more than 30 herbaria,
including 15 NSF-supported plant-related Thematic Collections Networks and
collaboratives. The workflows are provided for download as Portable Document
Format (PDF) and Microsoft Word files. Customization of these workflows for
specific institutional implementation is encouraged.
PMID- 26421258
TI - Limitations on the detection rate of high-risk HPV by hybrid capture 2
methodology in high grade intraepithelial (HSIL) or atypical squamous cells
cannot exclude HSIL (ASC-H) cytological lesions with proved CIN2.
AB - Recent literature data suggest that the high-risk human papillomaviruses (HR
HPVs) testing with several molecular techniques could be an alternative to
cytology in the detection of cervical intraepithelial neoplasias of grade 2 or
worse (CIN2+). However, any molecular techniques have its own limits and may give
false negative results which must be clearly known before undertaking a primary
HPV screening. This study aims to evaluate the performance of the high-risk HPV
hybrid capture II detection kit (HCII) which is considered as a "gold standard
technique" in a series of 100 women having proved both cytological lesions of
atypical squamous cells-cannot exclude an HSIL (ASC-H) or high-grade squamous
intraepithelial lesion (HSIL) and histological lesions of CIN2+. The clinical
sensitivity of HCII in women with a cytological diagnosis of ASC-H/HSIL and a
diagnosis of CIN2+ is high but not absolute and estimated at 96% (95,6% and 100%
of women with a diagnosis of CIN2/3 or invasive squamous cell carcinoma, resp.).
These data although they are infrequent must be clearly referred before to start
an HPV primary screening of CIN2+ especially with HCII methodology.
PMID- 26421259
TI - Minimization vs tailoring: Where do we stand with personalized immunosuppression
during renal transplantation in 2015?
AB - The introduction of novel immunosuppressive agents over the last two decades and
the improvement of our diagnostic tools for early detection of antibody-mediated
injury offer us an opportunity, if not a mandate, to better match the
immunosuppression needs of the individual patients with side effects of the
therapy. However, immunosuppressive regimens in the majority of programs remain
mostly protocol-driven, with relatively little inter-program heterogeneity in
certain areas of the world. Emerging data showing different outcomes with a
particular immunosuppressive strategy in populations with varying immunological
risks underscore a real potential for "personalized medicine" in renal
transplantation. Studies demonstrating marked differences in the adverse-effect
profiles of individual drugs including the risk for viral infections, malignancy
and renal toxicity call for a paradigm shift away from a "one size fits all"
approach to an individually tailored immunosuppressive therapy for renal
transplant recipients, assisted by both screening for predictors of graft loss
and paying close attention to dose or class-related adverse effects. Our paper
explores some of the opportunities during the care of these patients. Potential
areas of improvements may include: (1) a thorough assessment of immunological and
metabolic risk profile of each renal transplant recipient; (2) screening for
predictors of graft loss and early signs of antibody-mediated rejection with
donor-specific antibodies, protocol biopsies and proteinuria (including close
follow up of adverse effects with dose adjustments or conversions as necessary);
and (3) increased awareness of the possible link between poor tolerance of a
given drug at a given dose and non-adherence with the prescribed regimen.
Altogether, these considerations may enable the most effective use of the drugs
we already have.
PMID- 26421260
TI - Recent advances in post autologous transplantation maintenance therapies in B
cell non-Hodgkin lymphomas.
AB - Lymphomas constitute the second most common indication for high dose therapy
(HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The
intent of administering HDT in these heterogeneous disorders varies from cure
(e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent
lymphomas). Regardless of the underlying histology or remission status at
transplantation, disease relapse remains the number one cause of post auto-HCT
therapy failure and mortality. The last decade has seen a proliferation of
clinical studies looking at prevention of post auto-HCT therapy failure with
various maintenance strategies. The benefit of such therapies is in turn
dependent on disease histology and timing of transplantation. In relapsed,
chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT
maintenance rituximab seems to be safe and feasible, it does not provide improved
survival outcomes and is not recommended. The preliminary results with anti-
programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL
is promising but requires randomized validation. Similarly in follicular
lymphoma, maintenance therapies including rituximab following auto-HCT should be
considered investigational and offered only on a clinical trial. Rituximab
maintenance results in improved progression-free survival but has not yet shown
to improve overall survival in mantle cell lymphoma (MCL), but given the poor
prognosis with post auto-HCT failure in MCL, maintenance rituximab can be
considered on a case-by-case basis. Ongoing trials evaluating the efficacy of
post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1
inhibitors, proteasome inhibitors and bruton's tyrosine kinase inhibitors) will
likely change the practice landscape in the near future for B cell non-Hodgkin
lymphomas patients following HDT and auto-HCT.
PMID- 26421261
TI - Split liver transplantation: What's unique?
AB - The intraoperative management of split liver transplantation (SLT) has some
unique features as compared to routine whole liver transplantations. Only the
liver has this special ability to regenerate that confers benefits in survival
and quality of life for two instead of one by splitting livers. Primary graft
dysfunction may result from small for size syndrome. Graft weight to recipient
body weight ratio is significant for both trisegmental and hemiliver grafts.
Intraoperative surgical techniques aim to reduce portal hyperperfusion and
decrease venous portal pressure. Ischemic preconditioning can be instituted to
protect against ischemic reperfusion injury which impacts graft regeneration.
Advancement of the technique of SLT is essential as use of split cadaveric grafts
expands the donor pool and potentially has an excellent future.
PMID- 26421262
TI - Obesity and liver transplantation.
AB - The percentage of overweight and obese patients (OPs) waiting for a liver
transplant continues to increase. Despite the significant advances occurred in
bariatric medicine, obesity is still considered a relative contraindication to
liver transplantation (LT). The main aim of this review is to appraise the
literature on the outcomes of OPs undergoing LT, treatments that might reduce
their weight before, during or after surgery, and discuss some of the
controversies and limitations of the current knowledge with the intent of
highlighting areas where future research is needed.
PMID- 26421263
TI - Role of steroid maintenance in sensitized kidney transplant recipients.
AB - AIM: To evaluate whether there is a threshold sensitization level beyond which
benefits of chronic steroid maintenance (CSM) emerge. METHODS: Using Organ
Procurement and Transplant Network/United Network of Organ Sharing database, we
compared the adjusted graft and patient survivals for CSM vs early steroid
withdrawal (ESW) among patients who underwent deceased-donor kidney (DDK)
transplantation from 2000 to 2008 who were stratified by peak-panel reactive
antibody (peak-PRA) titers (0%-30%, 31%-60% and > 60%). All patients received
perioperative induction therapy and maintenance immunosuppression based on
calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF). RESULTS: The study
included 42851 patients. In the 0%-30% peak-PRA class, adjusted over-all graft
failure (HR 1.11, 95%CI: 1.03-1.20, P = 0.009) and patient-death (HR 1.29, 95%CI:
1.16-1.43, P < 0.001) risks were higher and death-censored graft-failure risk (HR
1.06, 95%CI: 0.98-1.14, P = 0.16) similar for CSM (n = 25218) vs ESW (n = 7399).
Over-all (HR 1.04, 95%CI: 0.85-1.28, P = 0.70) and death-censored (HR 0.97,
95%CI: 0.78-1.21, P = 0.81) graft-failure risks were similar and patient-death
risk (HR 1.39, 95%CI: 1.03-1.87, P = 0.03) higher for CSM (n = 3495) vs ESW (n =
850) groups for 31%-60% peak-PRA class. In the > 60% peak-PRA class, adjusted
overall graft-failure (HR 0.90, 95%CI: 0.76-1.08, P = 0.25) and patient-death (HR
0.92, 95%CI: 0.71-1.17, P = 0.47) risks were similar and death-censored graft
failure risk lower (HR 0.84, 95%CI: 0.71-0.99, P = 0.04) for CSM (n = 4966) vs
ESW (n = 923). CONCLUSION: In DDK transplant recipients who underwent
perioperative induction and CNI/MMF maintenance, CSM appears to be associated
with increased risk for death with functioning graft in minimally-sensitized
patients and improved death-censored graft survival in highly-sensitized
patients.
PMID- 26421264
TI - Effectiveness of repeated transplantations of hematopoietic stem cells in spinal
cord injury.
AB - AIM: To evaluate the short and long-term effects of the complex cell therapy of
202 cases of spinal cord injury (SCI). METHODS: The main arm included 202 cases
of SCI and the control arm included 20 SCI cases. For the therapy the
hematopoietic stem cells (HSCs) and progenitor cells (PCs) were mobilized to
peripheral blood by 8 subcutaneous injections of granulocyte colony-stimulating
factor (G-CSF) for 4 d and are harvested at day 5. The cells were administered to
the main arm intrathecally every 3 mo for a long term (3-5 years) according to
the internal research protocol international medical institute of tissue
engineering. Magnetic resonance imaging of the site of injury and urodynamic
tests were performed every 6 mo. Motor evoked potentials (MEP), somatosensory
evoked potentials (SSEP) were evaluated every 3 mo. The patients were evaluated
with american spianl injury association (ASIA) index, functional independence
measure index, the Medical Research Council Scale, the International Standards
for Neurological Classification of Spinal Cord Injury (ISCSCI-92) and
specifically developed scales. The function of bladder was evaluated by a
specifically developed clinical scale. The long-term clinical outcomes were
assessed for the SCI patients who received no less than 20 intrathecal
transplantations of HSCs and hematopoietic precursors (HPs). RESULTS: The
restoration of neurologic deficit after HSCs and HPs transplantations was proved
stable and evident in 57.4% of the cases. In 42.6% cases no neurologic
improvement has been observed. In 50% of the cases the motor restoration began
after the first transplantation, which is confirmed in average by 9.9 points
improvement in neurologic impairment as compared to the baseline (P < 0.05).
Repair of the urinary system was observed in 47.7% of the cases. The sensitivity
improved from baseline 124.3 points to 138.4 after the first and to 153.5 points
after the second transplantations of HSCs and HPs (P < 0.05, between the stages
of research). The evaluation with ASIA index demonstrated regress of neurologic
symptoms in 23 cases. Motor progress was also assessed with the ISCISCI-92 motor
and sensory scores, and the data coincided with those received with the
specifically developed scale. The number of the patients with the signs of
locomotive repair was 56.9%. No life threatening complications or adverse effects
have been observed. CONCLUSION: The method is safe, effective and considerably
improves the life quality of SCI patients. The therapy is approved for clinical
use as the treatment of choice.
PMID- 26421266
TI - Weight trends in United States living kidney donors: Analysis of the UNOS
database.
AB - AIM: To analyze the national trends associated with body mass index (BMI) and
living kidney donation. METHODS: Forty-seven thousand seven hundred and five
adult living kidney donors as reported to the Organ Procurement and
Transplantation Network from 1999 to 2011 were analyzed using their pre-donation
BMI. Predictor variables of interest included age, gender, ethnicity,
relationship, education status, and transplant region. RESULTS: Sixteen thousand
nine hundred and seventy-one of the living kidney donors were normal weight
(35.6%); 19337 were overweight (40.5%); 9007 were mildly obese (18.9%); 1992 were
moderate to morbidly obese (4.2%). Overweight and mildly obese kidney donors have
increased through time by 12% and 20% every 5 years, respectively (P < 0.05).
Donors 35-49 years of age, hispanic males or females and black females, those
with high school diploma or general Education Degree, and biologically related or
partner/spouses were more likely to be obese. CONCLUSION: Over the past 13 years,
the majority of living kidney donors have spanned the overweight to obese
categories. Paralleling the national rise is an increase in overweight and mildly
obese kidney donors. A fair number of moderate to morbidly obese living kidney
donors are still allowed to donate.
PMID- 26421265
TI - Cytomegalovirus reactivation after autologous stem cell transplantation in
myeloma and lymphoma patients: A single-center study.
AB - AIM: To determine the incidence of and the risk factors for cytomegalovirus (CMV)
symptomatic infection and end-organ disease after autologous stem cell
transplantation (ASCT). METHODS: A total of 327 consecutive non CD34(+) selected
autografts performed from the Hematology and Stem Cell Transplantation Unit of
Regina Elena National Cancer Institute of Rome (Italy) in the period comprised
between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201
were performed in patients with multiple myeloma, whereas the remaining 126 in
patients affected by non-Hodgkin's lymphoma and Hodgkin's lymphoma. The patients
who underwent an ASCT for an acute leukemia (n = 20) in the same period were
excluded from this analysis. CMV DNA load in the blood has been determined by
polymerase-chain reaction in the case of a clinical suspicion of reactivation,
therefore, no routine monitoring strategy was adopted. In the presence of signs
and symptoms of CMV reactivation an antiviral treatment was performed. RESULTS:
Overall, 36 patients (11%) required a specific antiviral treatment for a
symptomatic CMV reactivation (n = 32) or an end-organ disease (n = 4). We
observed 20 and 16 cases of CMV reactivation among lymphoma (16%) and myeloma
patients (8%), respectively. Among cases of end-organ disease, 3 were diagnosed
as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All
cases of CMV reactivation were observed in IgG seropositive patients, with no
documented cases of primary CMV infection. All patients were treated with a
specific antiviral therapy, with a global rate of hospitalization of 55%; four
patients received intravenous immunoglobulins. Transplant-related mortality was
significantly higher in patients who experienced a CMV reactivation (8.4% +/-
4.7% vs 1.7% +/- 0.8%; P = 0.047). In univariate analysis, a pre-transplant
HBcIgG seropositivity, a diagnosis of T-cell non-Hodgkin's lymphoma and higher
median age at transplant were significantly associated with the risk of
developing a clinically relevant CMV infection requiring specific antiviral
therapy (P < 0.001, P = 0.042 and P = 0.004, respectively). In multivariate
analysis, only a pre-transplant HBcIgG seropositivity (OR = 8.928, 95%CI: 1.991
33.321; P = 0.023) and a diagnosis of T-cell non-Hodgkin's lymphoma (OR = 4.739,
95%CI: 1.511-11.112; P = 0.042) proved to be independent predictors of a post
transplant clinically relevant CMV reactivation. CONCLUSION: A symptomatic CMV
infection can occur in about 11% of adult patients with lymphoma or myeloma
undergoing ASCT. A pre-transplant HBcIgG seropositivity and a diagnosis of T-cell
non-Hodgkin's lymphoma should be considered as independent predictor factors of
CMV reactivation.
PMID- 26421267
TI - Serum levels of soluble vascular cell adhesion molecules may correlate with the
severity of dengue virus-1 infection in adults.
AB - The damage of vascular endothelial cells has been speculated to be involved in
the pathogenesis of dengue virus (DENV) infection. However, little is known about
the role of soluble vascular cell adhesion molecule-1 (sVCAM-1) in predicting the
severity of dengue infection in adults. In this study, 51 adults with DENV-1
infection (21 with severe dengue and 30 with dengue fever (DF) were included, and
their serum levels of sVCAM-1 and other parameters were determined. The results
indicated that the levels of sVCAM-1 were elevated on days 1-3 to 16.75 (11.55
34.74) ng/mL in the severe dengue patients. These levels increased rapidly to
peak values of 43.53 (37.15-47.02) ng/mL on days 10-12 and then declined;
however, the values were maintained at a high level (38.07 (26.06-39.63) ng/mL).
Other parameters, including reduced platelet (PLT) counts, neutrophil (NEU)
counts and increased levels of alanine aminotransferase (ALT), aspartate
aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK),
were also observed in the severe dengue group but not in the DF group. The levels
of cytokines, such as interleukin (IL)-6, IL-10, interferon gamma (IFNgamma), and
tumor necrosis factor alpha (TNF-alpha), were transiently increased in the severe
dengue patients. Among the aforementioned parameters, only sVCAM-1 levels were
significantly elevated earlier and more persistently in the severe dengue
patients than in the DF patients. sVCAM-1 positively correlated with the levels
of ALT, AST, LDH, TNF-alpha, and IL-6 and negatively correlated with the levels
of PLT, NEU, and viremia. Notably, the high levels of sVCAM-1 were closely
associated with the severe dengue patients. In conclusion, sVCAM-1 may be a
superior indicator for monitoring the severity of dengue.
PMID- 26421269
TI - Large Dengue virus type 1 outbreak in Taiwan.
PMID- 26421268
TI - A sensitive and specific antigen detection assay for Middle East respiratory
syndrome coronavirus.
AB - Since its emergence in 2012, more than 900 laboratory-confirmed cases of Middle
East respiratory syndrome (MERS) have been reported with a fatality rate of more
than 30%. However, no antigen detection assay for commercial use is available for
diagnosis. In this study, the full-length nucleocapsid protein (NP) gene of MERS
coronavirus (MERS-CoV) was cloned and expressed in Escherichia coli. A MERS-CoV
NP capture enzyme-linked immunosorbent assay (ELISA) using two MERS-CoV-NP
specific monoclonal antibodies (MAbs) generated was developed. The ELISA was
evaluated using 129 nasopharyngeal aspirates (NPAs) positive for various
respiratory viruses and simulated positive NPAs by adding serial dilutions of
MERS-CoV. Using a cutoff OD of 0.19, all 129 NPAs positive for respiratory
viruses showed very low OD, with a specificity of 100%. For the two simulated
MERS-CoV-positive NPAs with serial dilutions of live MERS-CoV, all samples with
>=10 50% tissue culture infective dose (TCID50)/0.1 mL showed positive results.
For the 10 additional NPAs with 20 and 200 TCID50/0.1 mL of live MERS-CoV added,
all were positive. A highly sensitive and specific MAbs-based antigen capture
ELISA has been developed for MERS. This sensitive and specific antigen capture
ELISA should be useful for detection of MERS-CoV in human and dromedaries and in
field studies.
PMID- 26421270
TI - Outbreaks of enterovirus D68 in Malaysia: genetic relatedness to the recent US
outbreak strains.
PMID- 26421271
TI - Only a subset of C. canimorsus strains is dangerous for humans.
AB - Capnocytophaga canimorsus are gram-negative bacteria living as commensals in the
mouth of dogs and cats. C. canimorsus cause rare but life-threatening generalized
infections in humans that have been in contact with a dog or a cat. Over the last
years we collected 105 C. canimorsus strains from different geographical origins
and from severe human infections or healthy dogs. All these strains were analyzed
by 16S rDNA sequencing and a phylogenetic tree revealed two main groups of
bacteria instead of one with no relation to the geographical origin. This
branching was confirmed by the whole-genome sequencing of 10 strains, supporting
the evidence of a new Capnocytophaga species in dogs. Interestingly, 19 out of 19
C. canimorsus strains isolated from human infections belonged to the same
species. Furthermore, most strains from this species could grow in heat
inactivated human serum (HIHS) (40/46 tested), deglycosylate IgM (48/66) and were
cytochrome-oxidase positive (60/66) while most strains from the other species
could not grow in HIHS (22/23 tested), could not deglycosylate IgM (33/34) and
were cytochrome-oxidase negative (33/34). Here, we propose to call Capnocytophaga
canis (Latin: dog) the novel, presumably less virulent dog-hosted Capnocytophaga
species and to keep the name C. canimorsus for the species including human
pathogens.
PMID- 26421272
TI - Characterization of Listeria monocytogenes isolated from human Listeriosis cases
in China.
PMID- 26421273
TI - Persister mechanisms in Borrelia burgdorferi: implications for improved
intervention.
PMID- 26421276
TI - Advances in MRI Techniques and Applications.
PMID- 26421275
TI - Genomic Copy Number Variation Affecting Genes Involved in the Cell Cycle Pathway:
Implications for Somatic Mosaicism.
AB - Somatic genome variations (mosaicism) seem to represent a common mechanism for
human intercellular/interindividual diversity in health and disease. However,
origins and mechanisms of somatic mosaicism remain a matter of conjecture.
Recently, it has been hypothesized that zygotic genomic variation naturally
occurring in humans is likely to predispose to nonheritable genetic changes
(aneuploidy) acquired during the lifetime through affecting cell cycle
regulation, genome stability maintenance, and related pathways. Here, we have
evaluated genomic copy number variation (CNV) in genes implicated in the cell
cycle pathway (according to Kyoto Encyclopedia of Genes and Genomes/KEGG) within
a cohort of patients with intellectual disability, autism, and/or epilepsy, in
which the phenotype was not associated with genomic rearrangements altering this
pathway. Benign CNVs affecting 20 genes of the cell cycle pathway were detected
in 161 out of 255 patients (71.6%). Among them, 62 individuals exhibited >2 CNVs
affecting the cell cycle pathway. Taking into account the number of individuals
demonstrating CNV of these genes, a support for this hypothesis appears to be
presented. Accordingly, we speculate that further studies of CNV burden across
the genes implicated in related pathways might clarify whether zygotic genomic
variation generates somatic mosaicism in health and disease.
PMID- 26421274
TI - An Omics Perspective on Molecular Biomarkers for Diagnosis, Prognosis, and
Therapeutics of Cholangiocarcinoma.
AB - Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy arising from
the epithelial bile duct. The lack of early diagnostic biomarkers as well as
therapeutic measures results in severe outcomes and poor prognosis. Thus,
effective early diagnostic, prognostic, and therapeutic biomarkers are required
to improve the prognosis and prolong survival rates in CCA patients. Recent
advancement in omics technologies combined with the integrative experimental and
clinical validations has provided an insight into the underlying mechanism of CCA
initiation and progression as well as clues towards novel biomarkers. This work
highlights the discovery and validation of molecular markers in CCA identified
through omics approaches. The possible roles of these molecules in various
cellular pathways, which render CCA carcinogenesis and progression, will also be
discussed. This paper can serve as a reference point for further investigations
to yield deeper understanding in the complex feature of this disease, potentially
leading to better approaches for diagnosis, prognosis, and therapeutics.
PMID- 26421278
TI - mmnet: An R Package for Metagenomics Systems Biology Analysis.
AB - The human microbiome plays important roles in human health and disease. Previous
microbiome studies focused mainly on single pure species function and overlooked
the interactions in the complex communities on system-level. A metagenomic
approach introduced recently integrates metagenomic data with community-level
metabolic network modeling, but no comprehensive tool was available for such kind
of approaches. To facilitate these kinds of studies, we developed an R package,
mmnet, to implement community-level metabolic network reconstruction. The package
also implements a set of functions for automatic analysis pipeline construction
including functional annotation of metagenomic reads, abundance estimation of
enzymatic genes, community-level metabolic network reconstruction, and integrated
network analysis. The result can be represented in an intuitive way and sent to
Cytoscape for further exploration. The package has substantial potentials in
metagenomic studies that focus on identifying system-level variations of human
microbiome associated with disease.
PMID- 26421277
TI - Prognostic Outcomes and Risk Factors for Patients with Renal Cell Carcinoma and
Venous Tumor Thrombus after Radical Nephrectomy and Thrombectomy: The Prognostic
Significance of Venous Tumor Thrombus Level.
AB - INTRODUCTION: To evaluate the prognostic outcomes and risk factors for renal cell
carcinoma (RCC) patients with venous tumor thrombus in China. MATERIALS AND
METHODS: We reviewed the clinical information of 169 patients who underwent
radical nephrectomy and thrombectomy. Overall and cancer-specific survival rates
were analyzed. Univariate and multivariate analyses were used to investigate the
potential prognostic factors. RESULTS: The median survival time was 63 months.
The five-year overall survival and cancer-specific survival rate were 53.6% and
54.4% for all patients. For all patients, significant survival difference was
only observed between early (below hepatic vein) and advanced (above hepatic
vein) tumor thrombus. However, significant differences existed between both
RV/IVC and early/advanced tumor thrombus groups in N0M0 patients. Multivariate
analysis demonstrated that higher tumor thrombus level (p = 0.016, RR = 1.58), N
(p = 0.013, RR = 2.60), and M (p < 0.001, RR = 4.14) stages and adrenal gland
invasion (p = 0.001, RR = 4.91) were the most significant negative prognostic
predictors. CONCLUSIONS: In this study, we reported most cases of RCC patients
with venous extension in China. We proved that patients with RCC and venous tumor
thrombus may have relative promising long-term survival rate, especially those
with early tumor thrombus.
PMID- 26421279
TI - A Population-Based Model to Consider the Effect of Seasonal Variation on Serum
25(OH)D and Vitamin D Status.
AB - BACKGROUND: We elaborated a model that predicts the centiles of the 25(OH)D
distribution taking into account seasonal variation. METHODS: Data from two Swiss
population-based studies were used to generate (CoLaus) and validate (Bus Sante)
the model. Serum 25(OH)D was measured by ultra high pressure LC-MS/MS and
immunoassay. Linear regression models on square-root transformed 25(OH)D values
were used to predict centiles of the 25(OH)D distribution. Distribution functions
of the observations from the replication set predicted with the model were
inspected to assess replication. RESULTS: Overall, 4,912 and 2,537 Caucasians
were included in original and replication sets, respectively. Mean (SD) 25(OH)D,
age, BMI, and % of men were 47.5 (22.1) nmol/L, 49.8 (8.5) years, 25.6 (4.1)
kg/m(2), and 49.3% in the original study. The best model included gender, BMI,
and sin-cos functions of measurement day. Sex- and BMI-specific 25(OH)D centile
curves as a function of measurement date were generated. The model estimates any
centile of the 25(OH)D distribution for given values of sex, BMI, and date and
the quantile corresponding to a 25(OH)D measurement. CONCLUSIONS: We generated
and validated centile curves of 25(OH)D in the general adult Caucasian
population. These curves can help rank vitamin D centile independently of when
25(OH)D is measured.
PMID- 26421280
TI - Constructing a Genome-Wide LD Map of Wild A. gambiae Using Next-Generation
Sequencing.
AB - Anopheles gambiae is the major malaria vector in Africa. Examining the molecular
basis of A. gambiae traits requires knowledge of both genetic variation and
genome-wide linkage disequilibrium (LD) map of wild A. gambiae populations from
malaria-endemic areas. We sequenced the genomes of nine wild A. gambiae
mosquitoes individually using next-generation sequencing technologies and
detected 2,219,815 common single nucleotide polymorphisms (SNPs), 88% of which
are novel. SNPs are not evenly distributed across A. gambiae chromosomes. The low
SNP-frequency regions overlay heterochromatin and chromosome inversion domains,
consistent with the lower recombinant rates at these regions. Nearly one million
SNPs that were genotyped correctly in all individual mosquitoes with 99.6%
confidence were extracted from these high-throughput sequencing data. Based on
these SNP genotypes, we constructed a genome-wide LD map for wild A. gambiae from
malaria-endemic areas in Kenya and made it available through a public Website.
The average size of LD blocks is less than 40 bp, and several large LD blocks
were also discovered clustered around the para gene, which is consistent with the
effect of insecticide selective sweeps. The SNPs and the LD map will be valuable
resources for scientific communities to dissect the A. gambiae genome.
PMID- 26421281
TI - Expression Signatures of Long Noncoding RNAs in Adolescent Idiopathic Scoliosis.
AB - PURPOSE: Adolescent idiopathic scoliosis (AIS), the most common pediatric spinal
deformity, is considered a complex genetic disease. Causing genes and
pathogenesis of AIS are still unclear. This study was designed to identify
differentially expressed long noncoding RNAs (lncRNAs) involving the pathogenesis
of AIS. METHODS: We first performed comprehensive screening of lncRNA and mRNA in
AIS patients and healthy children using Agilent human lncRNA + mRNA Array V3.0
microarray. LncRNAs expression in different AIS patients was further evaluated
using quantitative PCR. RESULTS: A total of 139 lncRNAs and 546 mRNAs were
differentially expressed between AIS patients and healthy control. GO and Pathway
analysis showed that these mRNAs might be involved in bone mineralization,
neuromuscular junction, skeletal system morphogenesis, nucleotide and nucleic
acid metabolism, and regulation of signal pathway. Four lncRNAs
(ENST00000440778.1, ENST00000602322.1, ENST00000414894.1, and TCONS_00028768)
were differentially expressed between different patients when grouped according
to age, height, classification, severity of scoliosis, and Risser grade.
CONCLUSIONS: This study demonstrates the abnormal expression of lncRNAs and mRNAs
in AIS, and the expression of some lncRNAs was related to clinical features. This
study is helpful for further understanding of lncRNAs in pathogenesis, treatment,
and prognosis of AIS.
PMID- 26421282
TI - Functional Outcomes: One Year after a Cardiac Arrest.
AB - OBJECTIVE: The study aim was to characterize the time-course of recovery in
impairments, activity limitations, participation restrictions, disability, and
quality of life during the first year after cardiac arrest. Secondarily, the
study described the associations between the instruments used to measure each of
these domains. METHODS: Measures of global disability (Cerebral Performance
Category, CPC, Modified Rankin Scale, mRS), quality of life, activity
limitations, participation restrictions, and affective and cognitive impairments
were administered to 29 participants 1, 6, and 12 months after cardiac arrest.
RESULTS: Global measures of disability indicated recovery between one month and
one year after cardiac arrest (mean CPC: 2.1 versus 1.69, P < 0.05; mean mRS:
2.55 versus 1.83, P < 0.05). While global measures of disability were moderately
associated with participation, they were poorly associated with other measures.
The cohort endorsed depressive symptomatology throughout the year but did not
have detectable cognitive impairment. CONCLUSIONS: Recovery from cardiac arrest
is multifaceted and recovery continues for months depending upon the measures
being used. Measures of global disability, reintegration into the community, and
quality of life yield different information. Future clinical trials should
include a combination of measures to yield the most complete representation of
recovery after cardiac arrest.
PMID- 26421283
TI - Prevention of Nausea and Vomiting in Patients Undergoing Oral Anticancer
Therapies for Solid Tumors.
AB - Chemotherapy-induced nausea and vomiting (CINV) is still a common and
debilitating side effect despite recent advances in its prevention and treatment.
The intrinsic emetogenicity of chemotherapy agents allowed grouping into four
risk groups (high, moderate, low, and minimal risk of emetogenicity). The
prevention of acute and delayed CINV for intravenous agents and one day regimens
is well studied, although, there are few data about management of CINV induced by
oral cytotoxic agents and targeted therapies, usually administered in extended
regimens of daily oral use. Until now treatment of nausea and vomiting caused by
oral antineoplastic agents remains largely empirical. The level of evidence of
prophylactic antiemetics recommended for these agents is low. There are
differences in the classification of emetogenic potential of oral antineoplastic
agents between the international guidelines and different recommendations for
prophylactic antiemetic regimens. Herein we review the evidence for antiemetic
regimens for the most used oral antineoplastic agents for solid tumors and
propose antiemetic regimens for high to moderate risk and low to minimal risk of
emetogenicity.
PMID- 26421285
TI - Effects of a Particular Heptapeptide on the IFN-alpha-Sensitive CML Cells.
AB - Using the phage display biopanning technique, we have previously identified a
heptapeptide KLWVIPQ which specifically binds to the surface of the IFN-alpha
sensitive but not the IFN-alpha-resistant CML cells. The effects of this
heptapeptide on the IFN-alpha-sensitive CML cells were investigated in the
present study. IFN-alpha-sensitive KT-1/A3 and IFN-alpha-resistant KT-1/A3R CML
cells were transfected by pEGFP-KLWVIPQ expression vector and/or induced by IFN
alpha. WST-1 cell proliferation assay, flow cytometry, and western blotting were
performed to determine the effects of this heptapeptide and/or IFN-alpha on CML
cells. The viability of the KT-1/A3 cells was inhibited and apoptosis was induced
by either expression of the heptapeptide KLWVIPQ or IFN-alpha treatment with
concurrent upregulation of P53 and downregulation of P210(bcr/abl). However,
these effects were not observed in the IFN-alpha-resistant KT-1/A3R cells. These
results suggest that the heptapeptide KLWVIPQ shares a similar mechanism with IFN
alpha in the regulation of CML cell growth and apoptosis, implying that the
heptapeptide KLWVIPQ could be a novel target to go further into mechanisms of IFN
alpha sensitivity and/or resistance in CML.
PMID- 26421284
TI - Myocardial Dysfunction and Shock after Cardiac Arrest.
AB - Postarrest myocardial dysfunction includes the development of low cardiac output
or ventricular systolic or diastolic dysfunction after cardiac arrest. Impaired
left ventricular systolic function is reported in nearly two-thirds of patients
resuscitated after cardiac arrest. Hypotension and shock requiring vasopressor
support are similarly common after cardiac arrest. Whereas shock requiring
vasopressor support is consistently associated with an adverse outcome after
cardiac arrest, the association between myocardial dysfunction and outcomes is
less clear. Myocardial dysfunction and shock after cardiac arrest develop as the
result of preexisting cardiac pathology with multiple superimposed insults from
resuscitation. The pathophysiology involves cardiovascular ischemia/reperfusion
injury and cardiovascular toxicity from excessive levels of inflammatory cytokine
activation and catecholamines, among other contributing factors. Similar
mechanisms occur in myocardial dysfunction after cardiopulmonary bypass, in
sepsis, and in stress-induced cardiomyopathy. Hemodynamic stabilization after
resuscitation from cardiac arrest involves restoration of preload, vasopressors
to support arterial pressure, and inotropic support if needed to reverse the
effects of myocardial dysfunction and improve systemic perfusion. Further
research is needed to define the role of postarrest myocardial dysfunction on
cardiac arrest outcomes and identify therapeutic strategies.
PMID- 26421286
TI - Biomarkers of Brain Damage: S100B and NSE Concentrations in Cerebrospinal Fluid-
A Normative Study.
AB - NSE and S100B belong among the so-called structural proteins of the central
nervous system (CNS). Lately, this group of structural proteins has been
profusely used as specific biomarkers of CNS tissue damage. So far, the majority
of the research papers have focused predominantly on the concentrations of these
proteins in blood in relation to CNS damage of various origins. Considering the
close anatomic and functional relationship between the brain or spinal cord and
cerebrospinal fluid (CSF), in case of a CNS injury, a rapid and pronounced
increase of the concentrations of structural proteins specifically in CSF takes
place. This study inquires into the physiological concentrations of NSE and S100B
proteins in CSF, carried out on a sufficiently large group of 601 patients. The
detected values can be used for determination of a normal reference range in CSF
in a clinical laboratory diagnostics.
PMID- 26421288
TI - Biomarkers of Brain Function and Injury: Biological and Clinical Significance.
PMID- 26421287
TI - Evaluation of Liver Fibrosis Using Texture Analysis on Combined-Contrast-Enhanced
Magnetic Resonance Images at 3.0T.
AB - PURPOSE: To noninvasively assess liver fibrosis using combined-contrast-enhanced
(CCE) magnetic resonance imaging (MRI) and texture analysis. MATERIALS AND
METHODS: In this IRB-approved, HIPAA-compliant prospective study, 46 adults with
newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI
following intravenous administration of superparamagnetic iron oxides
(ferumoxides) and gadolinium DTPA (gadopentetate dimeglumine). The image texture
of the liver was quantified in regions-of-interest by calculating 165 texture
features. Liver biopsy specimens were stained with Masson trichrome and assessed
qualitatively (METAVIR fibrosis score) and quantitatively (% collagen stained
area). Using L 1 regularization path algorithm, two texture-based multivariate
linear models were constructed, one for quantitative and the other for
quantitative histology prediction. The prediction performance of each model was
assessed using receiver operating characteristics (ROC) and correlation analyses.
RESULTS: The texture-based predicted fibrosis score significantly correlated with
qualitative (r = 0.698, P < 0.001) and quantitative (r = 0.757, P < 0.001)
histology. The prediction model for qualitative histology had 0.814-0.976 areas
under the curve (AUC), 0.659-1.000 sensitivity, 0.778-0.930 specificity, and
0.674-0.935 accuracy, depending on the binary classification threshold. The
prediction model for quantitative histology had 0.742-0.950 AUC, 0.688-1.000
sensitivity, 0.679-0.857 specificity, and 0.696-0.848 accuracy, depending on the
binary classification threshold. CONCLUSION: CCE MRI and texture analysis may
permit noninvasive assessment of liver fibrosis.
PMID- 26421289
TI - Molecular Epidemiology of Human Norovirus in Korea in 2013.
AB - Norovirus is a major cause of acute gastroenteritis. The molecular epidemiology
of norovirus exhibits temporal and geographical fluctuations, and new variants of
the GII.4 genotype emerge every 2-3 years to cause global epidemics of acute
gastroenteritis. We investigated GI and GII genotypes of human norovirus strains
isolated from patients with acute gastroenteritis in Korea in 2013. Norovirus
antigen test was performed on 2,980 fecal specimens from January to December
2013. RNA was extracted from norovirus antigen-positive fecal suspensions, and
the norovirus capsid (VP1) and polymerase (RdRp) genes were characterized by RT
PCR and sequencing. Of the 230 genotyped strains, GII.4 (77.3%) was the most
frequently observed capsid genotype, followed by GII.3 (6.1%) and GII.13 (3.9%).
A norovirus GII.4 variant, GII.Pe/GII.4 Sydney 2012, was the most frequently
found polymerase/capsid genotype (65.7%), followed by GII.P17/GII.17 (2.1%) and
GII.P21/GII.3 (2.1%). Phylogenetic, similarity, and capsid epitope analyses of
GII.Pe/GII.4 Sydney 2012 strains were performed. We concluded that the norovirus
GII.4 variant, GII.Pe/GII.4 Sydney 2012, was the main cause of norovirus-related
gastroenteritis in Korea in 2013.
PMID- 26421290
TI - Cholesteryl Pullulan Encapsulated TNF-alpha Nanoparticles Are an Effective
Mucosal Vaccine Adjuvant against Influenza Virus.
AB - We encapsulated tumor necrosis factor-alpha (TNF-alpha), a major proinflammatory
cytokine, into cholesteryl pullulan (CHP) to prepare TNF/CHP nanoparticles. In
this report, we describe the immune-enhancing capability of the nanoparticles to
act as a vaccine adjuvant. TNF/CHP nanoparticles showed excellent storage
stability and enhanced host immune responses to external immunogens. The
nanoparticles were effective via the nasal route of administration for inducing
systemic IgG1 as well as mucosal IgA. We applied the nanoparticles in a model
experimental influenza virus infection to investigate their adjuvant ability.
TNF/CHP nanoparticles combined with a conventional split vaccine protected mice
via nasal administration against a lethal challenge of A/PR/8/34 (H1N1) influenza
virus. Mechanistic studies showed that the nanoparticles enhanced antigen uptake
by dendritic cells (DCs) and moderately induced the expression of inflammation
related genes in nasopharynx lymphoid tissue (NALT), leading to the activation of
both B and T cells. Preliminary safety study revealed no severe toxicity to
TNF/CHP nanoparticles. Slight-to-moderate influences in nasal mucosa were
observed only in the repeated administration and they seemed to be reversible.
Our data show that TNF/CHP nanoparticles effectively enhance both humoral and
cellular immunity and could be a potential adjuvant for vaccines against
infectious diseases, especially in the mucosa.
PMID- 26421292
TI - A Randomized, Double-Blind Pilot Study of Dose Comparison of Ramosetron to
Prevent Chemotherapy-Induced Nausea and Vomiting.
AB - PURPOSE: This study was conducted to determine the optimal dose titration of
ramosetron to prevent the Rhodes Index of Nausea, Vomiting, and Retching (RINVR).
METHODS: Patients treated with folic acid, 5-fluorouracil, and oxaliplatin were
randomized into three groups (0.3 mg, 0.45 mg, and 0.6 mg ramosetron before
chemotherapy). The pharmacokinetics and pharmacodynamics using RINVR were
evaluated. RESULTS: Seventeen, 15, and 18 patients received ramosetron at doses
of 0.3 mg, 0.45 mg, and 0.6 mg, respectively. T max (h), C max (ng/mL), and
AUClast (ng.h/mL) were associated with dose escalation significantly, showing a
reverse correlation with the RINVR during chemotherapy. Acute CINV was observed
in four patients (22.2%), two patients (14.3%), and one (5.6%) patient and a
delayed CINV on day 7 was found in eight (47%), three (21.4%), and five (27.8%)
patients in each group. The complete response rate was increased with dose
escalation (35.3%, 50.0%, and 72.2% in each group) and also showed the tendency
for decreasing moderate-to-severe CINV. CONCLUSIONS: This study shows a trend
regarding the dose-response relationship for ramosetron to prevent CINV,
including delayed emesis. It suggested that dose escalation should be considered
in patients with CINV in a subsequent cycle of chemotherapy, and an individual
approach using RINVR could be useful to monitor CINV.
PMID- 26421291
TI - Biological and Pharmacological Aspects of the NK1-Receptor.
AB - The neurokinin 1 receptor (NK-1R) is the main receptor for the tachykinin family
of peptides. Substance P (SP) is the major mammalian ligand and the one with the
highest affinity. SP is associated with multiple processes: hematopoiesis, wound
healing, microvasculature permeability, neurogenic inflammation, leukocyte
trafficking, and cell survival. It is also considered a mitogen, and it has been
associated with tumorigenesis and metastasis. Tachykinins and their receptors are
widely expressed in various human systems such as the nervous, cardiovascular,
genitourinary, and immune system. Particularly, NK-1R is found in the nervous
system and in peripheral tissues and are involved in cellular responses such as
pain transmission, endocrine and paracrine secretion, vasodilation, and
modulation of cell proliferation. It also acts as a neuromodulator contributing
to brain homeostasis and to sensory neuronal transmission associated with
depression, stress, anxiety, and emesis. NK-1R and SP are present in brain
regions involved in the vomiting reflex (the nucleus tractus solitarius and the
area postrema). This anatomical localization has led to the successful clinical
development of antagonists against NK-1R in the treatment of chemotherapy-induced
nausea and vomiting (CINV). The first of these antagonists, aprepitant (oral
administration) and fosaprepitant (intravenous administration), are prescribed
for high and moderate emesis.
PMID- 26421293
TI - How to Isolate a Plant's Hypomethylome in One Shot.
AB - Genome assembly remains a challenge for large and/or complex plant genomes due to
their abundant repetitive regions resulting in studies focusing on gene space
instead of the whole genome. Thus, DNA enrichment strategies facilitate the
assembly by increasing the coverage and simultaneously reducing the complexity of
the whole genome. In this paper we provide an easy, fast, and cost-effective
variant of MRE-seq to obtain a plant's hypomethylome by an optimized methyl
filtration protocol followed by next generation sequencing. The method is
demonstrated on three plant species with knowingly large and/or complex
(polyploid) genomes: Oryza sativa, Picea abies, and Crocus sativus. The
identified hypomethylomes show clear enrichment for genes and their flanking
regions and clear reduction of transposable elements. Additionally, genomic
sequences around genes are captured including regulatory elements in introns and
up- and downstream flanks. High similarity of the results obtained by a de novo
assembly approach with a reference based mapping in rice supports the
applicability for studying and understanding the genomes of nonmodel organisms.
Hence we show the high potential of MRE-seq in a wide range of scenarios for the
direct analysis of methylation differences, for example, between ecotypes,
individuals, within or across species harbouring large, and complex genomes.
PMID- 26421294
TI - Treatment of Breakthrough and Refractory Chemotherapy-Induced Nausea and
Vomiting.
AB - Despite significant progress in the prevention of chemotherapy-induced nausea and
vomiting (CINV) with the introduction of new antiemetic agents, 30-50% of
patients receiving moderately or highly emetogenic chemotherapy (MEC or HEC) and
guideline directed prophylactic antiemetics develop breakthrough CINV.
International guidelines recommend the treatment of breakthrough CINV with an
agent from a drug class that was not used in the prophylactic antiemetic regimen
and recommend using the breakthrough medication continuously rather than using it
on an as needed basis. There have been very few studies on the treatment of
breakthrough CINV. A recent double-blind, randomized, phase III study suggested
that olanzapine may be an effective agent for the treatment of breakthrough CINV.
Refractory CINV occurs when patients develop CINV during subsequent cycles of
chemotherapy when antiemetic prophylaxis has not been successful in controlling
CINV in earlier cycles. Patients who develop refractory CINV should be considered
for a change in their prophylactic antiemetic regimen. If significant anxiety
exists, a benzodiazepine may be added to the prophylactic regimen. If a
refractory patient is receiving HEC, olanzapine may be added to the prophylactic
regimen. If the patient is receiving MEC, olanzapine or an NK-1 receptor
antagonist may be added to the prophylactic regimen.
PMID- 26421295
TI - Growth Pattern of Clear Cell Renal Cell Carcinoma in Patients with Delayed
Surgical Intervention: Fast Growth Rate Correlates with High Grade and May Result
in Poor Prognosis.
AB - OBJECTIVES: Previous studies revealed an unclear correlation between the growth
rate of renal cell carcinoma (RCC) and tumor grade and did not focus on certain
histological subtype. This report investigated the correlation between the growth
rate and tumor grade in clear cell RCC (ccRCC). METHODS: We reviewed 60 patients
with 61 ccRCC confirmed by delayed surgeries after at least 12 months of active
surveillance. The linear growth rate (LGR), volumetric growth rate (VGR), and
volume doubling time (VDT) were calculated, and their correlations with
clinicopathologic characteristics were analyzed. RESULTS: The mean LGR, VGR, and
VDT were 0.86 (range 0-4.74) cm/year, 20.96 (range 0.31-211.93) cm(3)/year, and
667 (range 33-3321) days, respectively. ccRCCs with high grade had greater LGR (P
< 0.001) and VGR (P = 0.001) and lower VDT (P = 0.017) than ccRCCs with low
grade. Grade (OR = 5.185, P = 0.004) was the only independent risk factor of LGR
>0.5 cm/year, and grade (OR = 3.006, P = 0.046) and initial size (OR = 0.392, P =
0.004) were independent risk factors of VDT <1 year. Five patients developed
metastasis after surgery with LGR >0.5 cm/yr altogether; of them, four had cancer
related death by the last follow-up. CONCLUSIONS: Fast growth rate of ccRCC is
significantly correlated with high tumor grade and may result in poor prognosis,
especially for those with LGR >0.5 cm/yr.
PMID- 26421296
TI - Initial Experience of Sorafenib Neoadjuvant Therapy Combined with
Retroperitoneoscopy in Treating T2 Large Renal Carcinoma.
AB - OBJECTIVES: To investigate the safety and feasibility of sorafenib neoadjuvant
therapy combined with retroperitoneoscopic radical nephrectomy (RRN) in treating
T2 large renal cell carcinoma (RCC). METHODS: Retrospectively analyzed 5 cases (2
males and 3 females, aged 52-73 years) of T2 stage large RCC who receive
preoperative sorafenib targeted treatment (400 mg bid for 1-3 months) and RRN
between March, 2013, and July, 2014. Patient information, therapeutic regimen,
drug adverse effect, tumor changes before and after surgery, and perioperative
parameters were recorded. RESULTS: During the sorafenib therapy adverse effects
included 2 cases of hypertension (Grade I toxicity), 1 case of hand-foot syndrome
(Grade I), and 1 case of diarrhea (Grade II), which were all tolerable for
patients. CT scan and histopathological tests confirmed significant reduction in
the longest dimension (LD) and medium density (MD) of the tumor after therapy as
well as tumor hemorrhage, necrosis, and cystic degeneration. All 5 patients
received RRN surgery successfully around 2 weeks after drug discontinuation with
only 1 case of perioperative complication. CONCLUSIONS: Sorafenib neoadjuvant
therapy could significantly reduce the size and aggressiveness of T2 large renal
tumors, thus reducing the operative challenge and enabling patients who were
previously disqualified for operation to receive surgical treatment.
PMID- 26421297
TI - Age-Specific Gene Expression Profiles of Rhesus Monkey Ovaries Detected by
Microarray Analysis.
AB - The biological function of human ovaries declines with age. To identify the
potential molecular changes in ovarian aging, we performed genome-wide gene
expression analysis by microarray of ovaries from young, middle-aged, and old
rhesus monkeys. Microarray data was validated by quantitative real-time PCR.
Results showed that a total of 503 (60 upregulated, 443 downregulated) and 84
(downregulated) genes were differentially expressed in old ovaries compared to
young and middle-aged groups, respectively. No difference in gene expression was
found between middle-aged and young groups. Differentially expressed genes were
mainly enriched in cell and organelle, cellular and physiological process,
binding, and catalytic activity. These genes were primarily associated with KEGG
pathways of cell cycle, DNA replication and repair, oocyte meiosis and
maturation, MAPK, TGF-beta, and p53 signaling pathway. Genes upregulated were
involved in aging, defense response, oxidation reduction, and negative regulation
of cellular process; genes downregulated have functions in reproduction, cell
cycle, DNA and RNA process, macromolecular complex assembly, and positive
regulation of macromolecule metabolic process. These findings show that monkey
ovary undergoes substantial change in global transcription with age. Gene
expression profiles are useful in understanding the mechanisms underlying ovarian
aging and age-associated infertility in primates.
PMID- 26421298
TI - Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2
according to the Intrinsic Subtypes in Southern Han Chinese Women.
AB - GWAS have identified variation in the FGFR2 locus as risk factors for breast
cancer. Validation studies, however, have shown inconsistent results by ethnics
and pathological characteristics. To further explore this inconsistency and
investigate the associations of FGFR2 variants with breast cancer according to
intrinsic subtype (Luminal-A, Luminal-B, ER-&PR-&HER2+, and triple negative)
among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946,
rs2981579, and rs2981582 polymorphisms in 609 patients and 882 controls.
Significant associations with breast cancer risk were observed for rs2420946,
rs2981579, and rs2981582 with OR (95% CI) per risk allele of 1.19 (1.03-1.39),
1.24 (1.07-1.43), and 1.17 (1.01-1.36), respectively. In subtype specific
analysis, above three SNPs were significantly associated with increased Luminal-A
risk in a dose-dependent manner (P trend < 0.01); however, only rs2981579 was
associated with Luminal-B, and none were linked to ER-&PR- subtypes (ER-&PR
&HER2+ and triple negative). Haplotype analyses also identified common haplotypes
significantly associated with luminal-like subtypes (Luminal-A and Luminal-B),
but not with ER-&PR- subtypes. Our results suggest that associations of FGFR2
SNPs with breast cancer were heterogeneous according to intrinsic subtype. Future
studies stratifying patients by their intrinsic subtypes will provide new
insights into the complex genetic mechanisms underlying breast cancer.
PMID- 26421299
TI - Genetic Interactions Explain Variance in Cingulate Amyloid Burden: An AV-45 PET
Genome-Wide Association and Interaction Study in the ADNI Cohort.
AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder. Using
discrete disease status as the phenotype and computing statistics at the single
marker level may not be able to address the underlying biological interactions
that contribute to disease mechanism and may contribute to the issue of "missing
heritability." We performed a genome-wide association study (GWAS) and a genome
wide interaction study (GWIS) of an amyloid imaging phenotype, using the data
from Alzheimer's Disease Neuroimaging Initiative. We investigated the genetic
main effects and interaction effects on cingulate amyloid-beta (Abeta) load in an
effort to better understand the genetic etiology of Abeta deposition that is a
widely studied AD biomarker. PLINK was used in the single marker GWAS, and
INTERSNP was used to perform the two-marker GWIS, focusing only on SNPs with p <=
0.01 for the GWAS analysis. Age, sex, and diagnosis were used as covariates in
both analyses. Corrected p values using the Bonferroni method were reported. The
GWAS analysis revealed significant hits within or proximal to APOE, APOC1, and
TOMM40 genes, which were previously implicated in AD. The GWIS analysis yielded 8
novel SNP-SNP interaction findings that warrant replication and further
investigation.
PMID- 26421300
TI - A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for
Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced
Nausea and Vomiting.
AB - Combination antiemetic regimens targeting multiple molecular pathways associated
with emesis have become the standard of care for prevention of chemotherapy
induced nausea and vomiting (CINV) related to highly and moderately emetogenic
chemotherapies. Antiemetic consensus guidelines from several professional
societies are widely available and updated regularly as new data emerges.
Unfortunately, despite substantial research supporting the notion that guideline
conformity improves CINV control, adherence to antiemetic guidelines is
unsatisfactory. While studies are needed to identify specific barriers to
guideline use and explore measures to enhance adherence, a novel approach has
been taken to improve clinician adherence and patient compliance, with the
development of a new combination antiemetic. NEPA is an oral fixed combination of
a new highly selective NK1 receptor antagonist (RA), netupitant, and the
pharmacologically and clinically distinct 5-HT3 RA, palonosetron. This convenient
antiemetic combination offers guideline-consistent prophylaxis by targeting two
critical pathways associated with CINV in a single oral dose administered only
once per cycle. This paper will review and discuss the NEPA data in the context
of how this first combination antiemetic may overcome some of the barriers
interfering with adherence to antiemetic guidelines, enhance patient compliance,
and offer a possible advance in the prevention of CINV for patients.
PMID- 26421302
TI - Sex Differences in Immunology: More Severe Development of Experimental Pulmonary
Hypertension in Male Rats Exposed to Vascular Endothelial Growth Factor Receptor
Blockade.
AB - BACKGROUND: The epidemiology of pulmonary hypertension (PH) is characterized by a
female preponderance, whereas males share higher severity of the disease.
OBJECTIVE: To compare the severity of experimental PH between male and female
athymic rats. METHODS: PH was induced in 11 male and 11 female athymic rats
(resp., SU_M and SU_F groups) using an inhibitor of VEGF-receptors I and II,
semaxanib (40 mg/kg). After 28 days, right ventricular (RV) remodeling, systolic
function, and hemodynamics were measured using echocardiography and a pressure
volume admittance catheter. Morphometric analyses of lung vasculature and RV
myocardium were performed. RESULTS: Four weeks after semaxanib injection, RV end
systolic pressure was higher in SU_M than in SU_F. Males developed marked RV
enlargement and systolic dysfunction compared to females. Impairment of RV-PA
coupling efficiency was observed only in SU_M. The smooth muscle cells of the
pulmonary arteries switched from a contractile state to a dedifferentiated state
only in males. CONCLUSIONS: Female athymic rats were protected against the
development of severe PH. RV-PA coupling was preserved in females through
limitation of pulmonary artery muscularization. Control of smooth muscle cells
plasticity may be a promising therapeutic approach to reverse established
vascular remodeling in PH patients.
PMID- 26421301
TI - Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis.
AB - The procedure of neurogenesis has made numerous achievements in the past decades,
during which various molecular biomarkers have been emerging and have been
broadly utilized for the investigation of embryonic and adult neural stem cell
(NSC). Nevertheless, there is not a consistent and systematic illustration to
depict the functional characteristics of the specific markers expressed in
distinct cell types during the different stages of neurogenesis. Here we gathered
and generalized a series of NSC biomarkers emerging during the procedures of
embryonic and adult neural stem cell, which may be used to identify the
subpopulation cells with distinguishing characters in different timeframes of
neurogenesis. The identifications of cell patterns will provide applications to
the detailed investigations of diverse developmental cell stages and the extents
of cell differentiation, which will facilitate the tracing of cell time-course
and fate determination of specific cell types and promote the further and literal
discoveries of embryonic and adult neurogenesis. Meanwhile, via the utilization
of comprehensive applications under the aiding of the systematic knowledge
framework, researchers may broaden their insights into the derivation and
establishment of novel technologies to analyze the more detailed process of
embryogenesis and adult neurogenesis.
PMID- 26421303
TI - Usefulness of Nonenhanced Computed Tomography for Diagnosing Urolithiasis without
Pyuria in the Emergency Department.
AB - We compared the clinical utility of nonenhanced computed tomography (NECT) and
intravenous urography (IVU) in patients with classic symptoms of renal colic
without evidence of a urine infection. This was a retrospective analysis of IVU
and NECT performed in adult patients with suspected renal colic at an emergency
department between January 2005 and December 2013. The records of all patients in
NECT and IVU groups were reviewed, and the patients were categorized according to
the cause of their symptoms. A total of 2218 patients were enrolled. Of these
patients, 1525 (68.8%) underwent IVU and 693 (31.2%) underwent NECT. The patients
in NECT group were older (45.48 +/- 14.96 versus 42.37 +/- 13.68 years, p <
0.001), had less gross hematuria (7.6 versus 2.9%, p < 0.001), and were admitted
more often (18.6 versus 12.0%, p < 0.001) than the patients in IVU group. Urinary
stones were detected in 1413 (63.7%) patients. NECT had a higher detection rate
of urolithiasis than IVP (74.0 versus 59.0%, p < 0.001). No significant
difference was observed in the incidence of urinary stones greater than 4mm
between groups from the radiologic findings (p = 0.79) or the full medical record
review (p = 0.87).
PMID- 26421304
TI - Survey of Programs Used to Detect Alternative Splicing Isoforms from Deep
Sequencing Data In Silico.
AB - Next-generation sequencing techniques have been rapidly emerging. However, the
massive sequencing reads hide a great deal of unknown important information.
Advances have enabled researchers to discover alternative splicing (AS) sites and
isoforms using computational approaches instead of molecular experiments. Given
the importance of AS for gene expression and protein diversity in eukaryotes,
detecting alternative splicing and isoforms represents a hot topic in systems
biology and epigenetics research. The computational methods applied to AS
prediction have improved since the emergence of next-generation sequencing. In
this study, we introduce state-of-the-art research on AS and then compare the
research methods and software tools available for AS based on next-generation
sequencing reads. Finally, we discuss the prospects of computational methods
related to AS.
PMID- 26421305
TI - POD-1/TCF21 Reduces SHP Expression, Affecting LRH-1 Regulation and Cell Cycle
Balance in Adrenocortical and Hepatocarcinoma Tumor Cells.
AB - POD-1/TCF21 may play a crucial role in adrenal and gonadal homeostasis and
represses Sf-1/SF-1 expression in adrenocortical tumor cells. SF-1 and LRH-1 are
members of the Fzt-F1 subfamily of nuclear receptors. LRH-1 is involved in
several biological processes, and both LRH-1 and its repressor SHP are involved
in many types of cancer. In order to assess whether POD-1 can regulate LRH-1 via
the same mechanism that regulates SF-1, we analyzed the endogenous mRNA levels of
POD-1, SHP, and LRH-1 in hepatocarcinoma and adrenocortical tumor cells using qRT
PCR. Hereafter, these tumor cells were transiently transfected with pCMVMycPod-1,
and the effect of POD-1 overexpression on E-box elements in the LRH-1 and SHP
promoter region were analyzed by ChIP assay. Also, Cyclin E1 protein expression
was analyzed to detect cell cycle progression. We found that POD-1 overexpression
significantly decreased SHP/SHP mRNA and protein levels through POD-1 binding to
the E-box sequence in the SHP promoter. Decreased SHP expression affected LRH-1
regulation and increased Cyclin E1. These findings show that POD-1/TCF21
regulates SF-1 and LRH-1 by distinct mechanisms, contributing to the
understanding of POD-1 involvement and its mechanisms of action in adrenal and
liver tumorigenesis, which could lead to the discovery of relevant biomarkers.
PMID- 26421306
TI - 454-Pyrosequencing Analysis of Bacterial Communities from Autotrophic Nitrogen
Removal Bioreactors Utilizing Universal Primers: Effect of Annealing Temperature.
AB - Identification of anaerobic ammonium oxidizing (anammox) bacteria by molecular
tools aimed at the evaluation of bacterial diversity in autotrophic nitrogen
removal systems is limited by the difficulty to design universal primers for the
Bacteria domain able to amplify the anammox 16S rRNA genes. A metagenomic
analysis (pyrosequencing) of total bacterial diversity including anammox
population in five autotrophic nitrogen removal technologies, two bench-scale
models (MBR and Low Temperature CANON) and three full-scale bioreactors (anammox,
CANON, and DEMON), was successfully carried out by optimization of primer
selection and PCR conditions (annealing temperature). The universal primer 530F
was identified as the best candidate for total bacteria and anammox bacteria
diversity coverage. Salt-adjusted optimum annealing temperature of primer 530F
was calculated (47 degrees C) and hence a range of annealing temperatures of 44
49 degrees C was tested. Pyrosequencing data showed that annealing temperature of
45 degrees C yielded the best results in terms of species richness and diversity
for all bioreactors analyzed.
PMID- 26421307
TI - Molecular Detection of Equine Herpesvirus Types 1 and 4 Infection in Healthy
Horses in Isfahan Central and Shahrekord Southwest Regions, Iran.
AB - This study was undertaken to investigate molecularly the occurrence of EHV-1 and
EHV-4 infection among equine population in regions, Iran. Blood samples from 53
and 37 randomly selected horses settled in Isfahan and Shahrekord, Iran,
respectively, were collected. Detection of EHV-1 and EHV-4 genes in the blood
samples was done using polymerase chain reaction (PCR). Out of 53 and 37 samples
from Isfahan and Shahrekord, 4 (18.18%) and 3 (8.10%) were positive for PCR of
EHV-1, respectively. Nine (16.98%) and 6 (16.21%) were positive for PCR of EHV-4,
while 6 (11.32%) and 3 (8.10%) were positive for PCR of both EHV-1 and EHV-4, in
Isfahan and Shahrekord, respectively. Of the 7 blood samples positive for EHV-1,
4 (16.66%) and 3 (8.10%) were from horses >3 years old while 2 (18.18%) and 1
(16.66%) were from 2-3 years old horses, in Isfahan and Shahrekord, respectively.
Out of the 7 and 3 samples positive for PCR of EHV-1 in Isfahan and Shahrekord, 4
(22.2%) and 1 (7.69%) were Standardbred, while 3 (14.28%) and 2 (13.33%) were
Thoroughbreds, respectively. EHV-4 was detected in blood of 4 (22.22%) and 2
(15.83%) Standardbreds and from 4 (19.04%) and 4 (26.66%) Thoroughbred horses in
Isfahan and Shahrekord, respectively. This study has shown that horses settled in
Isfahan central and Shahrekord southwest regions, Iran, are infected by EHV-1 and
EHV-4 and thus serve as potential reservoirs and disseminators of the viruses.
PMID- 26421308
TI - Nailfold Capillaroscopy in Rheumatic Diseases: Which Parameters Should Be
Evaluated?
AB - Video nailfold capillaroscopy (NFC), considered as an extension of the widefield
technique, allows a more accurate measuring and storing of capillary data and a
better defining, analyzing, and quantifying of capillary abnormalities.
Capillaroscopic study is often performed on the patients suspected of having
microcirculation problems such as Raynaud's phenomenon as the main indication for
nailfold capillaroscopy. Capillaroscopic findings based on microcirculation
studies can provide useful information in the fields of pathophysiology,
differential diagnosis, and monitoring therapy. Nailfold capillaroscopy provides
a vital assessment in clinical practices and research; for example, its
reputation in the early diagnosis of systemic sclerosis is well established and
it is also used as a classification criterion in this regard. This review focuses
on the manner of performing video nailfold capillaroscopy and on a common
approach for measuring capillary dimensions in fingers and toes.
PMID- 26421310
TI - Phylogenetic Group Determination of Escherichia coli Isolated from Animals
Samples.
AB - This study analyzes the occurrence and distribution of phylogenetic groups of 391
strains of Escherichia coli isolated from poultry, cattle, and water buffalo. The
frequency of the phylogroups was A = 19%, B1 = 57%, B2 = 2.3%, C = 4.6%, D =
2.8%, E = 11%, and F = 3.3%. Phylogroups A (P < 0.001) and F (P = 0.018) were
associated with E. coli strains isolated from poultry, phylogroups B1 (P < 0.001)
and E (P = 0.002) were associated with E. coli isolated from cattle, and
phylogroups B2 (P = 0.003) and D (P = 0.017) were associated with E. coli
isolated from water buffalo. This report demonstrated that some phylogroups are
associated with the host analyzed and the results provide knowledge of the
phylogenetic composition of E. coli from domestic animals.
PMID- 26421311
TI - Computer Simulation and Field Experiment for Downlink Multiuser MIMO in Mobile
WiMAX System.
AB - The transmission performance for a downlink mobile WiMAX system with multiuser
multiple-input multiple-output (MU-MIMO) systems in a computer simulation and
field experiment is described. In computer simulation, a MU-MIMO transmission
system can be realized by using the block diagonalization (BD) algorithm, and
each user can receive signals without any signal interference from other users.
The bit error rate (BER) performance and channel capacity in accordance with
modulation schemes and the number of streams were simulated in a spatially
correlated multipath fading environment. Furthermore, we propose a method for
evaluating the transmission performance for this downlink mobile WiMAX system in
this environment by using the computer simulation. In the field experiment, the
received power and downlink throughput in the UDP layer were measured on an
experimental mobile WiMAX system developed in Azumino City in Japan. In
comparison with the simulated and experimented results, the measured maximum
throughput performance in the downlink had almost the same performance as the
simulated throughput. It was confirmed that the experimental mobile WiMAX system
for MU-MIMO transmission successfully increased the total channel capacity of the
system.
PMID- 26421309
TI - Potential Renoprotective Agents through Inhibiting CTGF/CCN2 in Diabetic
Nephropathy.
AB - Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD).
The development and progression of DN might involve multiple factors. Connective
tissue growth factor (CCN2, originally known as CTGF) is the one which plays a
pivotal role. Therefore, increasing attention is being paid to CCN2 as a
potential therapeutic target for DN. Up to date, there are also many drugs or
agents which have been shown for their protective effects against DN via
different mechanisms. In this review, we only focus on the potential
renoprotective therapeutic agents which can specifically abolish CCN2 expression
or nonspecifically inhibit CCN2 expression for retarding the development and
progression of DN.
PMID- 26421312
TI - Calibration of Smartphone-Based Weather Measurements Using Pairwise Gossip.
AB - Accurate and reliable daily global weather reports are necessary for weather
forecasting and climate analysis. However, the availability of these reports
continues to decline due to the lack of economic support and policies in
maintaining ground weather measurement systems from where these reports are
obtained. Thus, to mitigate data scarcity, it is required to utilize weather
information from existing sensors and built-in smartphone sensors. However, as
smartphone usage often varies according to human activity, it is difficult to
obtain accurate measurement data. In this paper, we present a heuristic-based
pairwise gossip algorithm that will calibrate smartphone-based pressure sensors
with respect to fixed weather stations as our referential ground truth. Based on
actual measurements, we have verified that smartphone-based readings are unstable
when observed during movement. Using our calibration algorithm on actual
smartphone-based pressure readings, the updated values were significantly closer
to the ground truth values.
PMID- 26421313
TI - Investigations into Recycling Zinc from Used Metal Oxide Varistors via pH
Selective Leaching: Characterization, Leaching, and Residue Analysis.
AB - Metal oxide varistors (MOVs) are a type of resistor with significantly nonlinear
current-voltage characteristics commonly used in power lines to protect against
overvoltages. If a proper recycling plan is developed MOVs can be an excellent
source of secondary zinc because they contain over 90 weight percent zinc oxide.
The oxides of antimony, bismuth, and to a lesser degree cobalt, manganese, and
nickel are also present in varistors. Characterization of the MOV showed that
cobalt, nickel, and manganese were not present in the varistor material at
concentrations greater than one weight percent. This investigation determined
whether a pH selective dissolution (leaching) process can be utilized as a
starting point for hydrometallurgical recycling of the zinc in MOVs. This
investigation showed it was possible to selectively leach zinc from the MOV
without coleaching of bismuth and antimony by selecting a suitable pH, mainly
higher than 3 for acids investigated. It was not possible to leach zinc without
coleaching of manganese, cobalt, and nickel. It can be concluded from results
obtained with the acids used, acetic, hydrochloric, nitric, and sulfuric, that
sulfate leaching produced the most desirable results with respect to zinc
leaching and it is also used extensively in industrial zinc production.
PMID- 26421315
TI - A Study on Suitability of EAF Oxidizing Slag in Concrete: An Eco-Friendly and
Sustainable Replacement for Natural Coarse Aggregate.
AB - Environmental and economic factors increasingly encourage higher utility of
industrial by-products. The basic objective of this study was to identify
alternative source for good quality aggregates which is depleting very fast due
to fast pace of construction activities in India. EAF oxidizing slag as a by
product obtained during the process in steel making industry provides great
opportunity to utilize it as an alternative to normally available coarse
aggregates. The primary aim of this research was to evaluate the physical,
mechanical, and durability properties of concrete made with EAF oxidizing slag in
addition to supplementary cementing material fly ash. This study presents the
experimental investigations carried out on concrete grades of M20 and M30 with
three mixes: (i) Mix A, conventional concrete mix with no material substitution,
(ii) Mix B, 30% replacement of cement with fly ash, and (iii) Mix C, 30%
replacement of cement with fly ash and 50% replacement of coarse aggregate with
EAF oxidizing slag. Tests were conducted to determine mechanical and durability
properties up to the age of 90 days. The test results concluded that concrete
made with EAF oxidizing slag and fly ash (Mix C) had greater strength and
durability characteristics when compared to Mix A and Mix B. Based on the overall
observations, it could be recommended that EAF oxidizing slag and fly ash could
be effectively utilized as coarse aggregate replacement and cement replacement in
all concrete applications.
PMID- 26421314
TI - Biological Events in Periodontal Ligament and Alveolar Bone Associated with
Application of Orthodontic Forces.
AB - Orthodontic force-induced stresses cause dynamic alterations within the
extracellular matrix and within the cytoskeleton of cells in the periodontal
ligament and alveolar bone, mediating bone remodelling, ultimately enabling
orthodontic tooth movement. In the periodontal ligament and alveolar bone, the
mechanically induced tensile strains upregulate the expression of osteogenic
genes resulting in bone formation, while mechanically induced compressive strains
mediate predominantly catabolic tissue changes and bone resorption. In this
review article we summarize some of the currently known biological events
occurring in the periodontal ligament and in the alveolar bone in response to
application of orthodontic forces and how these facilitate tooth movement.
PMID- 26421316
TI - Family Planning Knowledge, Attitudes, and Practices among Married Men and Women
in Rural Areas of Pakistan: Findings from a Qualitative Need Assessment Study.
AB - This paper presents the findings of a qualitative assessment aimed at exploring
knowledge, attitudes, and practices regarding family planning and factors that
influence the need for and use of modern contraceptives. A descriptive
exploratory study was conducted with married women and men aged between 15 and
40. Overall, 24 focus group discussions were conducted with male and female
participants in three provinces of Pakistan. The findings reveal that the
majority knew about some modern contraceptive methods, but the overall
contraceptive use was very low. Knowledge and use of any contraceptive method
were particularly low. Reasons for not using family planning and modern
contraception included incomplete family size, negative perceptions, in-laws'
disapproval, religious concerns, side-effects, and lack of access to quality
services. The majority preferred private facilities over the government health
facilities as the later were cited as derided. The study concluded the need for
qualified female healthcare providers, especially for long term family planning
services at health facilities instead of camps arranged occasionally. Addressing
issues around access, affordability, availability, and sociocultural barriers
about modern contraception as well as involving men will help to meet the needs
and ensure that the women and couples fulfill their childbearing and reproductive
health goals.
PMID- 26421318
TI - Evaluation of Factor VIII as a Risk Factor in Indian Patients with DVT.
AB - Introduction. Elevated factor VIII population in the Indian population has not
been studied as a possible risk factor for deep vein thrombosis (DVT). High
factor VIII level is considered a predisposing factor for DVT and its recurrence.
However it is known to vary between populations and its exact role in the
etiopathogenesis of thrombophilia remains unknown. Material and Methods. Factor
VIII levels of patients with DVT who had undergone a prothrombotic workup as a
part of their workup was compared to normal age matched controls in a 1 : 3
ratio. Results. There were 75 patients with DVT who had undergone a prothrombotic
workup in the course of their treatment for lower limb DVT. In these, 64% had
levels of factor VIII more than 150 as compared to 63% of normal controls (p >
0.05, not significant). Conclusion. Elevated factor VIII in the Indians may not
be associated with the same thrombotic risk as seen in the West. We find a
variation in the levels of factor VIII with a different "normal" than what is
reported in other populations. This needs further study to elucidate the role of
factor VIII in the evaluation and treatment of thrombophilia.
PMID- 26421317
TI - Normal Pregnancy Is Associated with Changes in Central Hemodynamics and Enhanced
Recruitable, but Not Resting, Endothelial Function.
AB - Introduction. Flow-mediated dilation (FMD), low flow-mediated constriction (L
FMC), and reactive hyperemia-related changes in carotid-to-radial pulse wave
velocity (DeltaPWVcr%) could offer complementary information about both
"recruitability" and "resting" endothelial function (EF). Carotid-to-femoral
pulse wave velocity (PWVcf) and pulse wave analysis-derived parameters (i.e.,
AIx@75) are the gold standard methods for noninvasive evaluation of aortic
stiffness and central hemodynamics. If healthy pregnancy is associated with both
changes in resting and recruitable EF, as well as in several arterial parameters,
it remains unknown and/or controversial. Objectives. To simultaneously and
noninvasively assess in healthy pregnant (HP) and nonpregnant (NP) women central
parameters in conjunction with "basal and recruitable" EF, employing new
complementary approaches. Methods. HP (n = 11, 34.2 +/- 3.3 weeks of gestation)
and age- and cardiovascular risk factors-matched NP (n = 22) were included.
Aortic blood pressure (BP), AIx@75, PWVcf, common carotid stiffness, and intima
media thickness, as well as FMD, L-FMC, and DeltaPWVcr %, were measured. Results.
Aortic BP, stiffness, and AIx@75 were reduced in HP. DeltaPWVcr% and FMD were
enhanced in HP in comparison to NP. No differences were found in L-FMC between
groups. Conclusion. HP is associated with reduced aortic stiffness, central BP,
wave reflections, and enhanced recruitable, but not resting, EF.
PMID- 26421319
TI - Recent progress in luminescence tuning of Ce(3+) and Eu(2+)-activated phosphors
for pc-WLEDs.
AB - Nowadays, phosphor converted white light-emitting diodes (pc-WLEDs) have been
widely used in solid-state lighting and display areas due to their superior
lifetime, efficiency, and reliability as well as significant reduction in power
consumption. Phosphors are indispensable components of pc-WLED devices, and their
luminescence properties determine the quality of WLED lighting and displays. In
order to further achieve high luminous efficacy, chromatic stability, and color
rending properties in pc-WLEDs, much effort has been focused on improving current
pc-WLED phosphors and developing novel pc-WLED phosphors recently. This review
article concerns commonly used rare earth ion (Eu(2+) and Ce(3+)) activated
inorganic phosphors, highlighting the important effect of spectral tuning via
local structural variations on improving the luminescence performance of
phosphors. The main spectral tuning strategies are discussed in detail and
summarized, including (1) doping level control; (2) cationic substitution; (3)
anionic substitution; (4) cationic-anionic substitution; (5) the crystal-site
engineering approach; (6) mixing of nanophases.
PMID- 26421321
TI - Photoinduced electron transfer as a design concept for luminescent redox
indicators.
AB - The general design principle for developing luminescent redox indicators based on
photoinduced electron transfer is described. The first part of the review
introduces colorimetric and fluorimetric redox indicators. The second part of the
review highlights recent developments regarding molecular luminescent redox
switches and logic gates. Potential future applications in biology, environmental
analysis, biomedical diagnostics, corrosion science and materials science are
mentioned.
PMID- 26421320
TI - Phage & phosphatase: a novel phage-based probe for rapid, multi-platform
detection of bacteria.
AB - Genetic engineering of bacteriophages allows for the development of rapid, highly
specific, and easily manufactured probes for the detection of bacterial
pathogens. A challenge for novel probes is the ease of their adoption in real
world laboratories. We have engineered the bacteriophage T7, which targets
Escherichia coli, to carry the alkaline phosphatase gene, phoA. This inclusion
results in phoA overexpression following phage infection of E. coli. Alkaline
phosphatase is commonly used in a wide range of diagnostics, and thus a signal
produced by our phage-based probe could be detected using common laboratory
equipment. Our work demonstrates the successful: (i) modification of T7 phage to
carry phoA; (ii) overexpression of alkaline phosphatase in E. coli; and (iii)
detection of this T7-induced alkaline phosphatase activity using commercially
available colorimetric and chemilumiscent methods. Furthermore, we demonstrate
the application of our phage-based probe to rapidly detect low levels of bacteria
and discern the antibiotic resistance of E. coli isolates. Using our
bioengineered phage-based probe we were able to detect 10(3) CFU per mL of E.
coli in 6 hours using a chemiluminescent substrate and 10(4) CFU per mL within
7.5 hours using a colorimetric substrate. We also show the application of this
phage-based probe for antibiotic resistance testing. We were able to determine
whether an E. coli isolate was resistant to ampicillin within 4.5 hours using
chemiluminescent substrate and within 6 hours using a colorimetric substrate.
This phage-based scheme could be readily adopted in labs without significant
capital investments and can be translated to other phage-bacteria pairs for
further detection.
PMID- 26421322
TI - Magnetic nanoparticles-cooperated fluorescence sensor for sensitive and accurate
detection of DNA methyltransferase activity coupled with exonuclease III-assisted
target recycling.
AB - A fluorescence magnetic biosensor for the DNA methyltransferase activity was
developed based on the cooperative amplification by combining the magnetic
nanoparticles synergistic exonuclease III (Exo III)-assisted circular exponential
amplification and a supramolecular structure ZnPPIX/G-quadruplex. First, a duplex
DNA probe, which was constructed by the hybridization of a quadruplex-forming
oligomer with a molecular beacon, was assembled on the magnetic nanoparticles
(MNPs) as a reporter. A hairpin probe (HP)-containing sequence of GATC was used
as the methylation substrate of DNA adenine methyltransferase (DAM). Once HP was
methylated by DAM, it could be recognized and cleaved by Dpn I, which allows the
release of a single-stranded DNA. The DNA (tDNA1) then hybridizes to the MNP
probe, which then triggers the exonuclease III-mediated target exponential
recycling reaction. Simultaneously, numerous quadruplex forming oligomers are
liberated and folded into the G-quadruplex-ZnPPIX complexes with the help of
zinc(ii)-protoporphyrin IX(ZnPPIX) on the MNP surface to give a remarkable
fluorescence response. In the developed sensor, a small amount of target DAM can
be converted to a large number of stable DNA triggers, leading to remarkable
amplification of the target. Moreover, using MNPs as a vector of the sensor may
reduce the interference from the real samples, which increases the anti
interference of the sensing system. Based on this unique amplification strategy,
a very low detection limit down to 2.0 * 10(-4) U mL(-1) was obtained.
Furthermore, the sensor could be used to evaluate the DAM activity in different
growth stages of E. coli cells and screen Dam MTase inhibitors. Therefore, the
strategy proposed here provides a promising platform for monitoring the activity
and inhibition of DNA MTases and has great potential to be applied further in
early clinical diagnostics and medical research.
PMID- 26421323
TI - An upconversion fluorescent resonant energy transfer biosensor for hepatitis B
virus (HBV) DNA hybridization detection.
AB - A novel fluorescent resonant energy transfer (FRET) biosensor was fabricated for
the detection of hepatitis B virus (HBV) DNA using poly(ethylenimine) (PEI)
modified upconversion nanoparticles (NH2-UCNPs) as energy donor and gold
nanoparticles (Au NPs) as acceptor. The PEI modified upconversion nanoparticles
were prepared directly with a simple one-pot hydrothermal method, which provides
high quality amino-group functionalized UCNPs with uniform morphology and strong
upconversion luminescence. Two single-stranded DNA strands, which were partially
complementary to each other, were then conjugated with NH2-UCNPs and Au NPs. When
DNA conjugated NH2-UCNPs and Au NPs are mixed together, the hybridization between
complementary DNA sequences on UCNPs and Au NPs will lead to the quenching of the
upconversion luminescence due to the FRET process. Meanwhile, upon the addition
of target DNA, Au NPs will leave the surface of the UCNPs and the upconversion
luminescence can be restored because of the formation of the more stable double
stranded DNA on the UCNPs. The sensor we fabricated here for target DNA detection
shows good sensitivity and high selectivity, which has the potential for clinical
applications in the analysis of HBV and other DNA sequences.
PMID- 26421325
TI - Photocatalytic CO2 reduction using visible light by metal-monocatecholato species
in a metal-organic framework.
AB - Metal-organic frameworks (MOFs) with isolated metal-monocatecholato groups have
been synthesized via postsynthetic exchange (PSE) for CO2 reduction photocatalyst
under visible light irradiation in the presence of 1-benzyl-1,4
dihydronicotinamide and triethanolamine. The Cr-monocatecholato species are more
efficient than the Ga-monocatecholato species.
PMID- 26421326
TI - A dinuclear Ru(II) complex capable of photoinduced ligand exchange at both metal
centers.
AB - {[Ru(CH3CN)3]2(tppz)}(4+) (tppz = tetra-2-pyridylpyrazine) undergoes photoinduced
CH3CN exchange with lambdairr >= 610 nm in H2O. In contrast, cis
{[Ru(tpy)(L)]2(bpm)}(4+) (tpy = 2,2':6',2''-terpyridine, bpm = 2,2'-bipyrimidine,
L = CH3CN) is not reactive, but the complex with L = DMSO is photoactive. These
complexes are potentially useful for the release of multiply caged drugs.
PMID- 26421324
TI - New supercharging reagents produce highly charged protein ions in native mass
spectrometry.
AB - The effectiveness of two new supercharging reagents for producing highly charged
ions by electrospray ionization (ESI) from aqueous solutions in which proteins
have native structures and reactivities were investigated. In aqueous solution, 2
thiophenone and 4-hydroxymethyl-1,3-dioxolan-2-one (HD) at a concentration of 2%
by volume can increase the average charge of cytochrome c and myoglobin by up to
163%, resulting in even higher charge states than those that are produced from
water/methanol/acid solutions in which these proteins are denatured. The greatest
extent of supercharging occurs in pure water, but these supercharging reagents
are also highly effective in aqueous solutions containing 200 mM ammonium acetate
buffer commonly used in native mass spectrometry (MS). These reagents are less
effective supercharging reagents than m-nitrobenzyl alcohol (m-NBA) and propylene
carbonate (PC) when ions are formed from water/methanol/acid. The extent to which
loss of the heme group from myoglobin occurs is related to the extent of
supercharging. Results from guanidine melts of cytochrome c monitored with
tryptophan fluorescence show that the supercharging reagents PC, sulfolane and HD
are effective chemical denaturants in solution. These results provide additional
evidence for the role of protein structural changes in the electrospray droplet
as the primary mechanism for supercharging with these reagents in native MS.
These results also demonstrate that for at least some proteins, the formation of
highly charged ions from native MS is no longer a significant barrier for
obtaining structural information using conventional tandem MS methods.
PMID- 26421327
TI - Lanthanide luminescent logic gate mimics in soft matter: [H(+)] and [F(-)] dual
input device in a polymer gel with potential for selective component release.
AB - The non-covalent incorporation of responsive luminescent lanthanide, Ln(III),
complexes with orthogonal outputs from Eu(III) and Tb(III) in a gel matrix allows
for in situ logic operation with colorimetric outputs. Herein, we report an
exemplar system with two inputs ([H(+)] and [F(-)]) within a p(HEMA-co-MMA)
polymer organogel acting as a dual-responsive device and identify future
potential for such systems.
PMID- 26421328
TI - Facile fabrication of cross-linked vesicle via "surface clicking" of calixarene
based supra-amphiphiles.
AB - A dynamic vesicle was constructed by the complexation of
(dodecyloxybenzyl)tripropargylammonium and p-sulfonatocalix[4]arene, then the
dynamic vesicle was cross-linked by a "click" reaction. The cross-linked vesicle
presents improved stability over the dynamic one. Meanwhile, it can be disrupted
with specific chemical stimuli to give the controlled release.
PMID- 26421329
TI - Chemical labeling of intracellular proteins via affinity conjugation and strain
promoted cycloadditions in live cells.
AB - A versatile chemical labeling approach was developed, where intracellular
proteins were first incorporated with a bioorthogonal group via affinity
conjugation, and subsequently labeled via strain-promoted cycloaddition reactions
in live cells.
PMID- 26421330
TI - Disseminated blastic plasmacytoid dendritic cell neoplasm.
PMID- 26421331
TI - Pseudoplatelets in acute myeloid leukemia.
PMID- 26421332
TI - Current Management of Fetal and Neonatal Tumors.
PMID- 26421333
TI - What Is the Optimal Duration of Advanced Physician Training?
PMID- 26421335
TI - Abstracts of the 11th International Congress on Systemic Lupus Erythematosus,
September 2-6, 2015, Vienna, Austria.
PMID- 26421336
TI - Nuts to You!--Every Day.
PMID- 26421337
TI - Animal Testing Ban Not for EU.
PMID- 26421338
TI - A Cure for Color Blindness? Stand by Buck Rogers!
PMID- 26421334
TI - Advances in the Science, Treatment, and Prevention of the Disease of Obesity:
Reflections From a Diabetes Care Editors' Expert Forum.
AB - As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular
disease, and numerous other detrimental conditions. The prevalence of obesity in
U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although
this trend may be leveling off, obesity and its individual, societal, and
economic costs remain of grave concern. In June 2014, a Diabetes Care Editors'
Expert Forum convened to review the state of obesity research and discuss the
latest prevention initiatives and behavioral, medical, and surgical therapies.
This article, an outgrowth of the forum, offers an expansive view of the obesity
epidemic, beginning with a discussion of its root causes. Recent insights into
the genetic and physiological factors that influence body weight are reviewed, as
are the pathophysiology of obesity-related metabolic dysfunction and the concept
of metabolically healthy obesity. The authors address the crucial question of how
much weight loss is necessary to yield meaningful benefits. They describe the
challenges of behavioral modification and predictors of its success. The effects
of diabetes pharmacotherapies on body weight are reviewed, including potential
weight-neutral combination therapies. The authors also summarize the evidence for
safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The
article concludes with an impassioned call for researchers, clinicians,
governmental agencies, health policymakers, and health-related industries to
collectively embrace the urgent mandate to improve prevention and treatment and
for society at large to acknowledge and manage obesity as a serious disease.
PMID- 26421340
TI - Withdrawal: Asymmetric Dimethylarginine and Endothelial Progenitor Cells After
Renal Transplantation: the Effect of Exercise Training.
PMID- 26421339
TI - Moderate Market Growth Predicted for Glaucoma Treatments.
PMID- 26421341
TI - The Social Origins of Networks and Diffusion.
AB - Recent research on social contagion has demonstrated significant effects of
network topology on the dynamics of diffusion. However, network topologies are
not given a priori. Rather, they are patterns of relations that emerge from
individual and structural features of society, such as population composition,
group heterogeneity, homophily, and social consolidation. Following Blau and
Schwartz, the author develops a model of social network formation that explores
how social and structural constraints on tie formation generate emergent social
topologies and then explores the effectiveness of these social networks for the
dynamics of social diffusion. Results show that, at one extreme, high levels of
consolidation can create highly balkanized communities with poor integration of
shared norms and practices. As suggested by Blau and Schwartz, reducing
consolidation creates more crosscutting circles and significantly improves the
dynamics of social diffusion across the population. However, the author finds
that further reducing consolidation creates highly intersecting social networks
that fail to support the widespread diffusion of norms and practices, indicating
that successful social diffusion can depend on moderate to high levels of
structural consolidation.
PMID- 26421342
TI - Go with Your Gut: Emotion and Evaluation in Job Interviews.
AB - This article presents hiring as an emotional process rooted in interpersonal
evaluation. Drawing from Randall Collins's theory of interaction ritual, the
author offers a qualitative case study of elite professional service firms to
unpack how employers' emotional reactions to applicants in job interviews affect
hiring evaluations. She finds that employers use subjective feelings of
excitement and enthusiasm toward candidates-akin to Collins's concept of
emotional energy--to-evaluate applicants and make hiring decisions. With these
data, she constructs an original theoretical framework of emotional energy
development, which highlights the qualities that tend to produce or inhibit the
subjective experience of emotional energy in job interviews. Additionally, she
outlines the particular phases of an encounter where energy gains and losses are
most consequential for influencing hiring outcomes and inequalities. She
discusses the implications of these findings for research on hiring, labor market
stratification, and interaction rituals.
PMID- 26421343
TI - Do Reputation Systems Undermine Trust? Divergent Effects of Enforcement Type on
Generalized Trust and Trustworthiness.
AB - Research shows that enforcing cooperation using contracts or tangible sanctions
can backfire, undermining people's intrinsic motivation to cooperate: when the
enforcement is removed, people are less trusting or trustworthy than when there
is no enforcement to begin with. The author examines whether reputation systems
have similar consequences for generalized trust and trustworthiness. Using a web
based experiment simulating online market transactions (studies 1 and 2), he
shows that reputation systems can reinforce generalized trust and
trustworthiness, unlike contractual enforcement or relational enforcement based
on repeated interactions. In a survey experiment (study 3), he finds that
recalling their eBay feedback scores made participants more trusting and
trustworthy. These results are predicated on the diffuse nature of reputational
enforcement to reinforce perceptions of trust and trustworthiness. These results
have implications for understanding how different forms of governance affect
generalized trust and trustworthiness.
PMID- 26421344
TI - Why Do Liberals Drink Lattes?
AB - Popular accounts of "lifestyle politics" and "culture wars" suggest that
political and ideological divisions extend also to leisure activities,
consumption, aesthetic taste, and personal morality. Drawing on a total of 22,572
pairwise correlations from the General Social Survey (1972-2010), the authors
provide comprehensive empirical support for the anecdotal accounts. Moreover,
most ideological differences in lifestyle cannot be explained by demographic
covariates alone. The authors propose a surprisingly simplesolution to the puzzle
of lifestyle politics. Computational experiments show how the self-reinforcing
dynamics of homophily and influence dramatically amplify even very small elective
affinities between lifestyle and ideology, producing a stereotypical world of
"latte liberals" and "bird-hunting conservatives" much like the one in which we
live.
PMID- 26421345
TI - Stress and Hardship after Prison.
AB - The historic increase in U.S. incarceration rates made the transition from prison
to community common for poor, prime-age men and women. Leaving prison presents
the challenge of social integration--of connecting with family and finding
housing and a means of subsistence. The authors study variation in social
integration in the first months after prison release with data from the Boston
Reentry Study, a unique panel survey of 122 newly released prisoners. The data
indicate severe material hardship immediately after incarceration. Over half of
sample respondents were unemployed, two-thirds received public assistance, and
many relied on female relatives for financial support and housing. Older
respondents and those with histories of addiction and mental illness were the
least socially integrated, with weak family ties, unstable housing, and low
levels of employment. Qualitative interviews show that anxiety and feelings of
isolation accompanied extreme material insecurity. Material insecurity combined
with the adjustment to social life outside prison creates a stress of transition
that burdens social relationships in high-incarceration communities.
PMID- 26421346
TI - Decreased baseline variability on fetal heart rate pattern in a fetus with
heterotaxy syndrome.
AB - In a fetus with suspected heterotaxy syndrome, a decreased/absent baseline
variability of fetal heart rate pattern developed at gestational week 36(+5) and
continued for 5 days until birth at gestational week 37(+2), while repeat
biophysical profile scorings with ultrasound were consistently unremarkable. This
neonate weighing 2404 g with Apgar scores of 7 (1-min) and 8 (5-min) and
umbilical arterial cord blood pH of 7.28 with base deficit of 3.9 mmol/L, showed
a heart rate of 120 b.p.m. for 3 h after birth, but subsequently developed sinus
bradycardia (84 b.p.m.) unresponsive to crying. Isoproterenol initiated 9 h after
birth was effective in the increase of heart rate to 120 b.p.m. in this neonate.
Brain magnetic resonance imaging at 16 days of age was unremarkable. The
decreased/absent baseline variability of fetal heart rate pattern was speculated
to have been caused by sinus node dysfunction, and not by reduced fetal
oxygenation in this case.
PMID- 26421347
TI - Editorial: Innovative practice.
PMID- 26421349
TI - Exploring Elements of Fun to Motivate Youth to Do Cognitive Bias Modification.
AB - OBJECTIVE: Heavy drinking among young adults poses severe health risks, including
development of later addiction problems. Cognitive retraining of automatic
appetitive processes related to alcohol (so-called cognitive bias modification
[CBM]) may help to prevent escalation of use. Although effective as a treatment
in clinical patients, the use of CBM in youth proves more difficult, as
motivation in this group is typically low, and the paradigms used are often
viewed as boring and tedious. This article presents two separate studies that
focused on three approaches that may enhance user experience and motivation to
train: a serious game, a serious game in a social networking context, and a
mobile application. MATERIALS AND METHODS: In the Game Study, 77 participants
performed a regular CBM training, aimed at response matching, a gamified version,
or a placebo version of that training. The gamified version was presented as a
stand-alone game or in the context of a social network. In the Mobile Study, 64
participants completed a different CBM training, aimed at approach bias, either
on a computer or on their mobile device. RESULTS: Although no training effects
were found in the Game Study, adding (social) game elements did increase aspects
of the user experience and motivation to train. The mobile training appeared to
increase motivation to train in terms how often participants trained, but this
effect disappeared after controlling for baseline motivation to train.
CONCLUSIONS: Adding (social) game elements can increase motivation to train, and
mobile training did not underperform compared with the regular training in this
sample, which warrants more research into motivational elements for CBM training
in younger audiences.
PMID- 26421350
TI - Stress and resolution in mothers of children with cerebral palsy.
AB - Parental resolution of diagnosis represents coming to terms with and accepting
the diagnosis of a serious condition in their child. As risk factors for
achieving resolution, we investigated: a child's functional status, cumulative
stress, and maternal depression. The current study tested the hypothesis that
mothers who are unresolved to their child's diagnosis would have considerably
higher levels of risk factors, compared to resolved mothers. We also examined
whether the observed risk factors could predict the resolution status. Maternal
resolution was assessed by means of the Reaction to Diagnosis Interview. The
sample consisted of 100 mothers of children aged 2-7, diagnosed with cerebral
palsy. The results showed that unresolved mothers had children with poorer
functional status, experienced more stressful life events, and were more
depressed compared to resolved ones. The functional status of a child and
maternal depression were shown to be significant resolution predictors.
Importantly, they were more successful in predicting the resolved than the
unresolved status. Further research is needed in order to investigate more
extensively the unresolved parental status.
PMID- 26421351
TI - Dissatisfaction with maintenance of certification in academic pediatrics.
PMID- 26421352
TI - Embodied Energy and GHG Emissions from Material Use in Conventional and
Unconventional Oil and Gas Operations.
AB - Environmental impacts embodied in oilfield capital equipment have not been
thoroughly studied. In this paper, we present the first open-source model which
computes the embodied energy and greenhouse gas (GHG) emissions associated with
materials consumed in constructing oil and gas wells and associated
infrastructure. The model includes well casing, wellbore cement, drilling mud,
processing equipment, gas compression, and transport infrastructure. Default case
results show that consumption of materials in constructing oilfield equipment
consumes ~0.014 MJ of primary energy per MJ of oil produced, and results in ~1.3
gCO2-eq GHG emissions per MJ (lower heating value) of crude oil produced, an
increase of 15% relative to upstream emissions assessed in earlier OPGEE model
versions, and an increase of 1-1.5% of full life cycle emissions. A case study of
a hydraulically fractured well in the Bakken formation of North Dakota suggests
lower energy intensity (0.011 MJ/MJ) and emissions intensity (1.03 gCO2-eq/MJ)
due to the high productivity of hydraulically fractured wells. Results are
sensitive to per-well productivity, the complexity of wellbore casing design, and
the energy and emissions intensity per kg of material consumed.
PMID- 26421353
TI - Seroprevalence and Serointensity of Latent Toxoplasma gondii in a Sample of
Elderly Adults With and Without Alzheimer Disease.
AB - INTRODUCTION: Latent infection with Toxoplasma gondii has been associated with
behavioral and cognitive changes in animal models and in humans. Early findings
have suggested an association between latent toxoplasmosis and Alzheimer disease
(AD). On the basis of these factors, we sought to determine whether there is an
association between latent toxoplasmosis and AD using a large, well-characterized
sample of subjects with AD and age-matched and sex-matched controls without
dementia. METHODS: Using ELISA, we determined anti-T. gondii IgG antibody titers
in 114 control subjects and in 105 subjects diagnosed with AD through an
Alzheimer's Disease Research Center. RESULTS: There were no group differences
between groups in age, ethnicity, or sex. Education and socioeconomic status was
slightly higher in the control group. Neither the prevalence of anti-T. gondii
IgG antibodies (33% in the nondemented control group compared with 41% in the AD
group, P=0.25) nor log-transformed antibody concentration (106.6 IU/mL in the
control group compared with 140.9 IU/mL in the AD group, P=0.85) differed between
the control and AD groups. DISCUSSION: In this sample, we found neither a higher
prevalence of latent toxoplasmosis in the AD group compared with the control
group nor differences in serum anti-T. gondii IgG titers between groups.
PMID- 26421354
TI - Heteronormativity and practitioner-patient interaction.
AB - Heteronormativity is the presumption of heterosexuality as the default sexual
orientation and can result in discrimination against the lesbian, gay, and
bisexual (LGB) population. This study serves as one of the first experimental
studies to examine heteronormative perceptions in communication and their effects
on practitioner-patient relationships. LGB participants were randomly assigned to
read either heteronormative or non-heteronormative vignettes of a doctor-patient
interaction. They then indicated how much health-relevant information they would
disclose to the doctor in the vignette and their level of trust in the doctor. In
the heteronormative condition, participants were less likely to disclose health
relevant information to the doctor in the vignette and were less trustful of the
doctor as compared to those in the non-heteronormative condition. These results
have important health implications, as lack of disclosure and trust may prevent
people from getting needed care and prevent doctors from giving the best health
advice possible. The results of this study provide further evidence that there is
a need for more education for all health care professionals to feel comfortable
while respectfully communicating with and treating patients who do not identify
as heterosexual in order to ensure the best health care experience.
PMID- 26421355
TI - Nonaqueous Dispersion Formed by an Emulsion Solvent Evaporation Method Using
Block-Random Copolymer Surfactant Synthesized by RAFT Polymerization.
AB - As surfactants for preparation of nonaqueous microcapsule dispersions by the
emulsion solvent evaporation method, three copolymers composed of stearyl
methacrylate (SMA) and glycidyl methacrylate (GMA) with different monomer
sequences (i.e., random, block, and block-random) were synthesized by reversible
addition-fragmentation chain transfer (RAFT) polymerization. Despite having the
same comonomer composition, the copolymers exhibited different functionality as
surfactants for creating emulsions with respective dispersed and continuous
phases consisting of methanol and isoparaffin solvent. The optimal monomer
sequence for the surfactant was determined based on the droplet sizes and the
stabilities of the emulsions created using these copolymers. The block-random
copolymer led to an emulsion with better stability than obtained using the random
copolymer and a smaller droplet size than achieved with the block copolymer.
Modification of the epoxy group of the GMA unit by diethanolamine (DEA) further
decreased the droplet size, leading to higher stability of the emulsion. The DEA
modified block-random copolymer gave rise to nonaqueous microcapsule dispersions
after evaporation of methanol from the emulsions containing colored dyes in their
dispersed phases. These dispersions exhibited high stability, and the particle
sizes were small enough for application to the inkjet printing process.
PMID- 26421356
TI - Social Welfare Expenditures and Infant Mortality.
AB - This study examines the effects of social welfare expenditures on infant
mortality (deaths younger than age 1 per 1,000 live births) across 19
Organisation for Economic Co-operation and Development (OECD) countries from 1980
to 2010. Data are obtained from various sources including the OECD, World Health
Organization, and World Bank. The findings indicate that among three social
welfare expenditure measures for families, the expenditures on family cash
allowances are predicted to reduce infant mortality. However, the other two
measures-the expenditures on parental and maternity leave and expenditures on
family services-have no significant effects on infant mortality.
PMID- 26421358
TI - Let's talk about society: A Critical Discourse Analysis of sociology courses in
pre-registration nursing.
AB - BACKGROUND: The discussion of teaching and learning in nursing has been prolific.
Whereas most of the debate tends to focus on core contents of nursing programmes,
little has been discussed about the teaching in 'supporting subjects' with
relevance to both nursing education and nursing practice. This article offers a
perspective on sociology scholarship for applied professions by using the case of
nursing programmes. METHODOLOGY: Syllabus is a rich source of data, and in its
representational capacity it becomes both a discursive construction and a vehicle
of ideology. Accordingly, we present a Critical Discourse Analysis of syllabi of
nursing schools in Chile as to identify core contents and ideologies, and implied
challenges for nursing education. FINDINGS AND DISCUSSION: We argue that while
the syllabus as a discourse discloses a significant cleavage, the biggest
challenge is precisely to challenge the ideologies constructed by and embedded in
the syllabi. Our reflection thus points to a better interdisciplinary dialogue as
to enhance the actual contribution of sociology to nursing.
PMID- 26421357
TI - Tris DBA palladium overcomes hypoxia-mediated drug resistance in multiple
myeloma.
AB - Despite recent progress in novel and targeted therapies, multiple myeloma (MM)
remains a therapeutically challenging incurable disease. The regulation of
important cellular processes and its link to cancer presented Src as an
attractive target for MM. We suggest a novel strategy to improve the treatment of
MM and overcome the drug resistance for the current therapeutic agents by
specific inhibition of Src in MM cells by Tris (Dibenzylideneacetone) dipalladium
(Tris DBA). Tris DBA reduces proliferation, induces G1 arrest and apoptosis in MM
cells. Tris DBA showed additive effect with proteasome inhibitors reducing
proliferation, cell cycle signaling, and increasing apoptosis more than each drug
alone. Tris DBA overcame hypoxia-induced effects such as enhanced chemotaxis or
drug resistance to proteasome inhibitors by inhibition of HIF1alpha expression.
Moreover, we found that Tris DBA is an effective anti-myeloma agent alone or in
combination with other targeted drugs and that it reverses hypoxia-induced drug
resistance in myeloma.
PMID- 26421359
TI - Protective effect of resveratrol against neuronal damage following transient
global cerebral ischemia in mice.
AB - Resveratrol (3,5,4'-trihydroxystilbene) is a natural polyphenol which is rich in
grape seeds and skin. Several studies have revealed that resveratrol possesses
neuroprotective effects. In the case of global brain ischemia, there are few
reports regarding the protective effect of resveratrol. Therefore, the influence
of resveratrol on neuronal damage after transient global brain ischemia remains
to be clarified. In the current study, C57BL/6 black mice were subjected to 20
min of transient global brain ischemia and followed by 72 h of reperfusion.
Resveratrol (20 or 40 mg/kg, once daily, dissolved in 0.5%
carboxymethylcellulose) was administered orally for 7 days before ischemia and
daily until the mice were euthanized. The effect of lower or higher dose of
resveratrol on neuronal damage, matrix metalloproteinase (MMP) activity and in
situ DNA fragmentation (TUNEL) assay in the hippocampus after global ischemia was
examined. Neuronal damages were remarkable in CA1 and CA2 pyramidal cell layers
after global ischemia. In resveratrol-treated mice (40 mg/kg), neuronal damage
was significantly reduced compared with vehicle-treated mice. Mice treated with
resveratrol showed reduced MMP-9 activity. Resveratrol also inhibited TUNEL
staining. These data suggest that resveratrol, a natural polyphenol, reduces
hippocampal neuronal cell damage following transient global ischemia by reducing
MMP-9 activity.
PMID- 26421360
TI - In situ synthesis of TiO2(B) nanotube/nanoparticle composite anode materials for
lithium ion batteries.
AB - Titania nanotubes were prepared by a simple hydrothermal route. Their
electrochemical performance has been examined in detail and compared to TiO2(B)
nanoparticles, TiO2 anatase and P25 titania nanoparticles. The cycling and rate
performance of TiO2 nanotubes is superior to both types of nanoparticles, and it
can be further improved by an in situ titanium precursor treatment, which results
in the formation of TiO2 nanoparticles on/between the nanotubes. The obtained
specific capacity after 200 cycles at 0.2 A g(-1) charge/discharge rate remained
above 130 mAh g(-1). The enhanced lithium storage properties of these samples can
be attributed to their unique morphology and crystal structure.
PMID- 26421361
TI - Women's views and knowledge regarding healthcare seeking for gestational diabetes
in the postpartum period: A systematic review of qualitative/survey studies.
AB - AIM: To identify factors influencing postpartum healthcare seeking, from the
perspective of women who have experienced gestational diabetes mellitus (GDM).
METHODS: Systematic review that searched PubMed, Web of Science, EMBASE and
CINAHL on 27th February 2013. Qualitative studies and surveys, with women as
participants, which reported pre-specified outcomes, including barriers and
facilitators to healthcare seeking for GDM after birth, were included. Two
authors independently extracted data and assessed quality. Results were
thematically synthesised. RESULTS: Forty-two studies were included, with data
from 7949 women in several countries. The diagnosis of GDM was sometimes a
concerning or upsetting experience. A need for more specific information about
GDM to be available around the time of diagnosis was identified. Women had varied
experiences of antenatal GDM care and management, ranging from very positive to
difficult and confusing. Non-judgemental and positively focussed care was
preferred. While women were often knowledgeable about type 2 diabetes risk and
prevention, they faced multiple barriers to undertaking preventive behaviours. A
need for lifestyle change support and more pro-active postpartum care was
identified. CONCLUSIONS: Provision of improved GDM education, as well as positive
and pro-active care from diagnosis until postpartum follow-up may increase
healthcare seeking by women with recent GDM.
PMID- 26421362
TI - mTOR inhibitors and diabetes.
AB - The mammalian target of rapamycin (mTOR) inhibitors are drugs, primarily used as
immunosuppressors that are now frequently used as antineoplastic therapies in
various cancers (such as advanced renal cell carcinoma, advanced breast cancer,
progressive pancreatic neuroendocrine tumors). They act on mTOR signaling pathway
which plays a key role in regulating cell growth as well as lipid and glucose
metabolism. Treatment with mTOR inhibitors is associated with a high incidence of
hyperglycemia and new-onset diabetes, ranging from 13% to 50% in the clinical
trials in which they have been used as anticancer therapies. The rate of severe
hyperglycemia is also increased, ranging from 4 to 12% in the main phase III
clinical trials. Due to limited human studies, the pathophysiology of mTOR
inhibitor-induced hyperglycemia has not yet been totally clarified. However, data
from animal studies suggest that the mechanisms responsible for hyperglycemia
with mTOR inhibitors are likely due to the combination of impaired insulin
secretion and insulin resistance. Due to the high rate of hyperglycemia
associated with the use of mTOR inhibitors, a close and personalized follow-up of
blood glucose is recommended in all patients.
PMID- 26421363
TI - How does thiol/disulfide homeostasis change in prediabetic patients?
AB - AIMS: Our aim was to examine thiol/disulfide homeostasis, which has a critical
role in many cellular activities such as antioxidant protection, detoxification,
cell growth and apoptosis, in prediabetic patients. METHODS: The study population
was formed of a total of 250 participants; 125 (54 males, 71 females) of which
were newly diagnosed with prediabetes, aged over 18 and who had not received any
prior treatment and 125 (52 males, 73 females) healthy volunteers. Prediabetic
patients were diagnosed using a glucose tolerance test. In both groups, native
thiol-disulfide exchanges were examined using the automated measurement method
newly developed by Erel and Neselioglu. RESULTS: When compared to the control
group, the native thiol (p<0.001) and total thiol (p=0.008) levels, and the
native thiol/total thiol (p=0.022) ratio was lower; while disulfide (p=0.001)
level and, disulfide/native thiol (p=0.003) and disulfide/total thiol (p=0.022)
ratios were higher in prediabetic patients. A positive correlation was determined
between disulfide and the fasting blood glucose levels (r=0.394, p=0.017) and
glycolysed hemoglobin (HbA1c) (r=0.307, p=0.011). On the other hand, a negative
correlation was determined between native thiol and fasting blood glucose levels
(r=-0.335, p=0.004). CONCLUSION: With this study, we have shown for the first
time that thiol oxidation increases in prediabetic patients and that there is a
positive correlation between the disulfide and blood glucose and HbA1c levels.
PMID- 26421364
TI - Comparison between indexes of insulin resistance for risk prediction of
cardiovascular diseases or development of diabetes.
AB - AIM: The predictive effect of various insulin resistance indexes for risk of
cardiovascular diseases (CVD) or type 2 diabetes (T2DM) is still unclear.
METHODS: One thousand and forty-nine 71-years-old male subjects from the Swedish
ULSAM study, mean follow-up 9 years. All subjects performed the euglycemic
insulin clamp for M/I [glucose disposal/mean insulin], and 75-g oral glucose
tolerance test for Ceder-IR: 1/glucose uptake rate/[mean glucose*log mean
insulin]; Matsuda-IR: 1/10,000/square root
[glucose0*insulin0*glucose120*insulin120]; Belfiore-IR:
1/([glucose0+glucose120]/normal mean glucose*[insulin0+insulin120]/normal mean
insulin)+1); and HOMA-IR: [glucose0*insulin0]/22.5. RESULTS: Bland-Altman plots
showed best agreement between M/I versus Belfiore-IR and Ceder-IR with mean
difference near zero, -0.21 to -0.46, while -0.68 to -0.77 for the other indexes.
ISI-Ceder was the strongest predictor for incident nonfatal/fatal ischemic heart
disease (CHD) or CVD at Cox regression in all subjects, and for incident T2DM at
logistic regression in 1024 subjects with no baseline T2DM, with significantly
higher hazard ratios or odds ratios than with all other indexes, also with best
model fit, after adjusting for clinical characteristics and the traditional
cardiovascular risk factors, including metabolic syndrome for CVD risk.
CONCLUSION: Ceder-IR performed strongest as independent predictor for incidences
of CHD/CVD and T2DM.
PMID- 26421365
TI - H7N9 Influenza Virus Is More Virulent in Ferrets than 2009 Pandemic H1N1
Influenza Virus.
AB - The novel H7N9 influenza virus has been infecting humans in China since February
2013 and with a mortality rate of about 40%. This study compared the
pathogenicity of the H7N9 and 2009 pandemic H1N1 influenza viruses in a ferret
model, which shows similar symptoms to those of humans infected with influenza
viruses. The H7N9 influenza virus caused a more severe disease than did the 2009
pandemic H1N1 influenza virus. All of the ferrets infected with the H7N9
influenza virus had died by 6 days after infection, while none of those infected
with the 2009 pandemic H1N1 influenza virus died. Ferrets infected with the H7N9
influenza virus had higher viral titers in their lungs than did those infected
with the 2009 pandemic H1N1 influenza virus. Histological findings indicated that
hemorrhagic pneumonia was caused by infection with the H7N9 influenza virus, but
not with the 2009 pandemic H1N1 influenza virus. In addition, the lung tissues of
ferrets infected with the H7N9 influenza virus contained higher levels of
chemokines than did those of ferrets infected with the 2009 pandemic H1N1
influenza virus. This study suggests that close monitoring is needed to prevent
human infection by the lethal H7N9 influenza virus.
PMID- 26421367
TI - A comparative study of APLI and APCI in IMS at atmospheric pressure to reveal and
explain peak broadening effects by the use of APLI.
AB - The details of the ionization mechanism in atmospheric pressure are still not
completely known. In order to obtain further insight into the occurring processes
in atmospheric pressure laser ionization (APLI) a comparative study of
atmospheric pressure chemical ionization (APCI) and APLI is presented in this
paper. This study is carried out using similar experimental condition at
atmospheric pressure employing a commercial ion mobility spectrometer (IMS). Two
different peak broadening mechanisms can then be assigned, one related to a range
of different species generated and detected, and furthermore for the first time a
power broadening effect on the signals can be identified.
PMID- 26421368
TI - Doxycycline sclerotherapy in children with head and neck lymphatic malformations.
AB - OBJECTIVE: This is a systematic review of the literature describing doxycycline
sclerotherapy (DS) to treat pediatric head and neck lymphatic malformations and
examine patient factors associated with treatment success. DATA SOURCES: PubMed,
EMBASE, and Ovid. REVIEW METHODS: A query of PubMed, EMBASE, and Ovid search
engines (1995-2014) for studies examining outcomes for doxycycline sclerotherapy
(DS) as primary treatment strategy for children with head and neck lymphatic
malformations was undertaken. Successful outcome was defined as clinical
resolution of symptoms or greater than 50% reduction in radiographic involvement.
RESULTS: Five studies met the inclusion criteria for review. All were
retrospective case series reports with high risk of bias. The dose of doxycycline
used in all but one of the studies was 10mg/mL, and the highest concentration
administered was 20mg/mL. Thirty-eight children met the inclusion criteria for
analysis. Thirty-two (84.2%) children were successfully treated with DS, with 23
(60.5%) utilizing only one treatment session. Average follow-up was 9.7months.
Age, gender, de Serres stage 1, and type of lymphatic malformation were not
related to successful treatment outcome (p=0.23, 1, 1, and 0.13, respectively).
CONCLUSIONS: DS is very effective for treatment of macrocystic and mixed head and
neck lymphatic malformations in children. Overall success with DS treatment in
children with lymphatic malformation of the head and neck was 84.2%. DS has
distinct advantages over other sclerotherapy agents including that it is
inexpensive and widely available, and has minimal side effects. No associated
patient characteristics were found to predict improved success.
PMID- 26421366
TI - PGC-1alpha/ERRalpha-Sirt3 Pathway Regulates DAergic Neuronal Death by Directly
Deacetylating SOD2 and ATP Synthase beta.
AB - AIMS: Parkinson's disease (PD) heavily affects humans and little is known about
its cause and pathogenesis. Sirtuin 3 (Sirt3) plays a key role in regulating
mitochondrial dysfunction, which is the main cause of DAergic neuronal loss in
PD. We investigated the mechanisms of neuroprotective role of Sirt3 in DAergic
neuronal survival. RESULTS: Sirt3 was reduced in 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine (MPTP)-treated neurons with its overexpression being
neuroprotective. We identified that Sirt3 interacted with manganese superoxide
dismutase (SOD2) and adenosine triphosphate (ATP) synthase beta and modulated
their activities by deacetylating SOD2 (K130) and ATP synthase beta (K485) to
prevent reactive oxygen species accumulation and ATP depletion, and to alleviate
DAergic neuronal death upon MPTP treatment. Peroxisome proliferator-activated
receptor-gamma coactivator 1alpha (PGC-1alpha) interacted with estrogen-related
receptor alpha (ERRalpha) that bound to the Sirt3 promoter as its transcription
factor to regulate Sirt3 expression and DAergic neuronal death. In the mouse
midbrain, MPTP administration led to the loss of PGC-1alpha and Sirt3, high
acetylation level of SOD2 and ATP synthase beta, and the specific loss of DAergic
neurons, while Sirt3 overexpression could protect against DAergic neuronal loss.
Sirt3 knockout mice exhibited more sensitive and more DAergic neuronal loss to
MPTP treatment. INNOVATION: The study provides new insights into a critical PGC
1alpha/ERRalpha-Sirt3 pathway, linking regulation of mitochondrial protein
acetylation and DAergic neuronal death in PD pathogenesis, which provide a
potential therapeutic strategy and target in PD treatment. CONCLUSION: These
results provide a vital PGC-1alpha/ERRalpha-Sirt3 pathway that protects against
DAergic neuronal death by directly deacetylating SOD2 (K130) and ATP synthase
beta (K485) in PD.
PMID- 26421369
TI - Crowdsourcing to Assess Surgical Skill.
PMID- 26421371
TI - Psoriasis and the Risk of Depression in the US Population: National Health and
Nutrition Examination Survey 2009-2012.
AB - IMPORTANCE: Psoriasis is a risk factor for depression. Depression may also
trigger or exacerbate psoriasis. The relationship between psoriasis and
depression, however, remains to be fully explored. OBJECTIVE: To investigate the
association between psoriasis and major depression in the US population. DESIGN,
SETTING, AND PARTICIPANTS: Population-based study using participants in the
National Health and Nutrition Examination Survey from 2009 through 2012. MAIN
OUTCOMES AND MEASURES: Diagnosis of major depression based on the Patient Health
Questionnaire-9. RESULTS: We identified 351 (2.8%) cases of psoriasis and 968
(7.8%) cases of major depression among 12,382 US citizens included in our study.
Fifty-eight (16.5%) patients with psoriasis met criteria for a diagnosis of major
depression. The mean (SD) Patient Health Questionnaire-9 score was significantly
higher among patients with a history of psoriasis than those without psoriasis
(4.54 [5.7] vs 3.22 [4.3], P < .001). Psoriasis was significantly associated with
major depression, even after adjustment for sex, age, race, body mass index,
physical activity, smoking history, alcohol use, history of myocardial infarction
(MI), history of stroke, and history of diabetes mellitus (OR, 2.09 [95% CI, 1.41
3.11], P < .001). Interaction term analyses involving patients with a history of
both psoriasis and a cardiovascular event, specifically MI or stroke, did not
reveal a synergistically increased risk of major depression (psoriasis and MI:
OR, 1.09 [95% CI, 0.28-3.60], P = .91; psoriasis and stroke: OR, 0.67 [95% CI,
0.12-3.66], P = .63). In adjusted multivariable models, the risk of major
depression was not significantly different between patients with limited vs
extensive psoriasis (OR, 0.66 [95% CI, 0.18-2.44], P = .53). CONCLUSIONS AND
RELEVANCE: Self-reported history of psoriasis was independently associated with
major depression as assessed by a validated screening tool, even when controlling
for comorbidities. History of cardiovascular event did not modify the risk of
major depression for patients with psoriasis. The severity of psoriasis was
unrelated to the risk of major depression. Therefore, all patients with
psoriasis, regardless of severity, may be at risk for major depression.
PMID- 26421370
TI - Motility of liquid stored ram spermatozoa is altered by dilution rate independent
of seminal plasma concentration.
AB - The fertility after use of liquid stored ram semen following cervical AI rapidly
decreases if semen is stored beyond 12h. The dilution of seminal plasma is often
cited as a key contributor to the diminished motility and fertility of ram
spermatozoa subjected to liquid preservation. Two experiments were conducted to
assess the effect of spermatozoa concentration (i.e. dilution rate) and
percentage of seminal plasma on the motility and viability of liquid stored ram
spermatozoa. In Experiment 1, semen was diluted to one of seven concentrations
ranging from 0.2 to 1.4*10(9)spermatozoa/ml with milk and assessed for motility
after 3 or 24h of storage at 15 degrees C. In Experiment 2, semen was collected
and washed to remove seminal plasma before re-dilution to 0.2
1.4*10(9)spermatozoa/ml with milk containing 0%, 20% or 40% (final v/v ratio)
seminal plasma and assessed for viability and motility after 3 or 24h of storage
at 15 degrees C. Whereas motility was not affected by spermatozoa concentration
after 3h of storage, the proportion of progressive spermatozoa decreased after
24h of storage when spermatozoa concentration was greater than
1.0*10(9)spermatozoa/ml. The duration of preservation and the spermatozoa
concentration affected spermatozoa motility but had no impact on spermatozoa
viability. This negative effect of greater spermatozoa concentrations on motility
was independent of the presence and the concentration of seminal plasma. The
seminal plasma at both concentrations (20% and 40%) had a protective effect on
spermatozoa motility after 24h of storage. These findings have the potential to
improve the efficiency of cervical AI with liquid stored ram semen.
PMID- 26421372
TI - Mortality Risk Prediction: Can Comorbidity Indices Be Improved With Psychosocial
Data?
AB - BACKGROUND: Predicting risk of premature death is one of the most basic tasks in
medicine and public health, but has proven to be difficult over the long term
even with the best prognostic models. One popular strategy has been to improve
prognostic models with candidate genes and other novel biomarkers. However, the
gains in predictive power have been modest and the costs have been high, leading
to a demand for cost-effective alternatives. We conducted a proof-of-principle
investigation to examine whether simple, cheap, and noninvasive paper-and-pencil
measures of social class and personality phenotype could improve the performance
of one of the most widely used prediction models for all-cause mortality, the
Charlson Comorbidity Index (CCI). METHODS: We used data from baseline and 25-year
mortality follow-up of the UK Health and Lifestyle Study cohort. In a subset of
the cohort, we first identified 5 psychosocial factors highly predictive of
mortality: income, education, type A personality, communalism (preference for the
company of others), and "lie" scale (a measure of denial, putatively associated
with ill health). We then examined the predictive performance of the CCI with and
without these measures in a validation subsample. RESULTS: Across 5-, 10-, 15-,
20-, and 25-year time horizons, the psychosocially augmented CCI showed
substantially better discrimination [area under the receiver-operating curves
(95% confidence interval) from 0.83 (0.81-0.85) to 0.84 (0.83-0.86)] than the CCI
[area under the receiver-operating curves from 0.74 (0.71-0.76) to 0.77 (0.76
0.79)]. These translated into net reclassification improvements from 27% (23%
31%) to 35% (32%-38%) of survivors and from 23% (17%-30%) to 34% (17%-30%) of
decedents; and 23%-42% reductions in the Number Needed to Screen. Calibration
improved at all time horizons except 25 years, where it was decreased.
CONCLUSION: Widespread attempts to improve prognostic models might consider not
only novel biomarkers, but also psychosocial questionnaire measures.
PMID- 26421373
TI - Have Racial Disparities in Ambulatory Care Sensitive Admissions Abated Over Time?
AB - BACKGROUND: Racial disparities in access to care and access to high-quality care
have been persistent over many decades. They have been documented in all areas of
health care, including ambulatory care. Policy initiatives have been implemented
to address disparities and close the gaps in care that minorities face. Less is
known about the effectiveness of these polices. OBJECTIVES: To evaluate whether
disparities in quality of ambulatory care have abated during the decade of 2000
by answering 2 questions: (1) were there differences in ambulatory care sensitive
hospital admissions rates by race?; (2) have these differences been declining
over time? RESEARCH DESIGN: Multivariable linear regressions with fixed county
effects and robust SEs of longitudinal panel data. SUBJECTS: A total of 4,032,322
discharges in 172 counties in 6 states during 2003-2009. MEASURES: Prevention
Quality Indicators (PQIs) developed by the Agency for Healthcare Research and
Quality, by county, and race calculated from the Healthcare Cost and Utilization
Project dataset. RESULTS: In 2003 the overall PQI admission rates were higher for
African Americans (around 16.5/1000) than for whites (around 15/1000). By 2009,
the overall and the chronic PQI admission rates declined significantly (P<0.01)
for whites. They either did not decline or increased for African Americans. Acute
PQI rates declined significantly for whites and remained stable for African
Americans. CONCLUSIONS: Policies addressing persisting racial disparities in
quality of ambulatory care for African Americans should focus on the chronic
PQIs. In addition, efforts should be made to improve data quality for race and
ethnicity information on hospital discharge data to enable informed policy
evaluation and planning.
PMID- 26421374
TI - Experimental Realization of Two Decoupled Directional Couplers in a Subwavelength
Packing by Adiabatic Elimination.
AB - On-chip optical data processing and photonic quantum integrated circuits require
the integration of densely packed directional couplers at the nanoscale. However,
the inherent evanescent coupling at this length scale severely limits the
compactness of such on-chip photonic circuits. Here, inspired by the adiabatic
elimination in a N-level atomic system, we report an experimental realization of
a pair of directional couplers that are effectively isolated from each other
despite their subwavelength packing. This approach opens the way to ultradense
arrays of waveguide couplers for integrated optical and quantum logic gates.
PMID- 26421376
TI - Systemic sclerosis: a rare cause of heart failure?
AB - Systemic sclerosis (SS) is a chronic disease in which there may be multisystem
involvement. It is rare (estimated prevalence: 0.5-2/10000) with high morbidity
and mortality, and there is as yet no curative treatment. We report the case of a
young woman newly diagnosed with SS, in whom decompensated heart failure was the
main manifestation.
PMID- 26421377
TI - High-sensitivity C-reactive protein in obese children: too complex a marker to
use?
PMID- 26421378
TI - Iron metabolism in heart failure: mechanisms and therapeutic approaches.
PMID- 26421379
TI - A 75-year-old woman with chest pain and transient severe left ventricular
systolic dysfunction.
AB - INTRODUCTION: Coronary spasm can cause myocardial ischemia and angina in both
patients with and without obstructive coronary artery disease. However,
provocation tests using intracoronary acetylcholine (ACh) have been rarely
performed in the Western world. CASE REPORT: We report a case of a 75-year-old
woman with a history of hypertension and a mechanical aortic prosthesis who
presented in the emergency room with acute-onset chest pain, widespread ST
segment depression and severe left ventricular systolic dysfunction, with no
signs of prosthesis dysfunction. Emergent coronary angiography excluded
obstructive coronary artery disease. Pain relief and normalization of ST segment
and systolic function occurred within six hours. The patient was treated for a
possible thromboembolic myocardial infarction and was discharged home
asymptomatic. Two weeks later, cardiac magnetic resonance was performed showing
inferoseptal transmural infarct scar, inferior and inferolateral subendocardial
infarct and mid-basal ischemia in the anterior and anterolateral walls. She was
readmitted with recurrence of chest pain and it was decided to perform a
provocation test with ACh. After injection of ACh into the left anterior
descending artery, chest pain, ST-segment depression, blood flow impairment (TIMI
1) and transient grade 3 atrioventricular (AV) block occurred. Intracoronary
administration of nitrates reversed the coronary spasm and AV conduction
disturbances. Twenty minutes later, chest pain and ischemic ST changes recurred;
there was no response to vasodilators and the patient developed cardiac arrest
with pulseless electrical activity. Advanced life support was maintained for 32
minutes without return of spontaneous circulation. CONCLUSIONS: Provocation tests
have a high sensitivity and specificity for the diagnosis of vasospastic angina.
Although it is rare, these tests have the potential risk of irreversible spasm
leading to arrhythmia and death.
PMID- 26421380
TI - Synthesis of beta-C-Glycopyranosyl Aldehydes and 2,6-Anhydro-heptitols.
AB - A convenient route has been developed for the diastereoselective synthesis of
beta-C-glycopyranosyl aldehydes from D-glucose, D-mannose, and D-galactose. The
key step in the synthesis of C-glycosyl aldehydes is the aryl driven reductive
dehydration on 1-phenyl-2-(2',3',4',6'-tetra-O-acetyl-beta-D
glycopyranosyl)ethanone to afford alkenes, which on oxidation afford the desired
compounds in good yield. beta-C-Glycopyranosyl aldehydes have been converted to
2,6-anhydro-heptitols in quantitative yields. The 2,6-anhydro-heptitols derived
from D-mannose and D-galactose are enantiomeric and are useful linkers for the
synthesis of macrocycles/amphiphiles of complementary chirality.
PMID- 26421381
TI - Spectroscopic and MD simulation studies on unfolding processes of mitochondrial
carbonic anhydrase VA induced by urea.
AB - Carbonic anhydrase VA (CAVA) is primarily expressed in the mitochondria and
involved in numerous physiological processes including lipogenesis, insulin
secretion from pancreatic cells, ureagenesis, gluconeogenesis and neuronal
transmission. To understand the biophysical properties of CAVA, we carried out a
reversible urea-induced isothermal denaturation at pH 7.0 and 25 degrees C.
Spectroscopic probes, [theta]222 (mean residue ellipticity at 222 nm), F344 (Trp
fluorescence emission intensity at 344 nm) and Deltaepsilon280 (difference
absorption at 280 nm) were used to monitor the effect of urea on the structure
and stability of CAVA. The urea-induced reversible denaturation curves were used
to estimate [Formula: see text], Gibbs free energy in the absence of urea; Cm,
the mid-point of the denaturation curve, i.e. molar urea concentration ([urea])
at which DeltaGD = 0; and m, the slope (=?DeltaGD/?[urea]). Coincidence of
normalized transition curves of all optical properties suggests that
unfolding/refolding of CAVA is a two-state process. We further performed 40 ns
molecular dynamics simulation of CAVA to see the dynamics at different urea
concentrations. An excellent agreement was observed between in silico and in
vitro studies.
PMID- 26421382
TI - Sodium-Ion Storage in Pyroprotein-Based Carbon Nanoplates.
AB - Pyroprotein-based carbon nanoplates are fabricated from self-assembled silk
proteins as a versatile platform to examine sodium-ion storage characteristics in
various carbon environments. It is found that, depending on the local carbon
structure, sodium ions are stored via chemi-/physisorption, insertion, or
nanoclustering of metallic sodium.
PMID- 26421383
TI - Dynamics of pelvic floor muscle functional parameters and their correlations with
urinary incontinence in men after radical prostatectomy.
AB - AIMS: To evaluate the dynamics of pelvic floor muscle strength, endurance, and
urinary incontinence in a 6-month period in men after radical prostatectomy and
to determine correlations between pelvic floor muscle strength, endurance, and
urinary incontinence. METHODS: Forty-two men with prostate cancer treated with
radical prostatectomy participated in the study. Pelvic floor muscles parameters
were evaluated using the anal perineometer. An 8-hour pad test was used with the
catheter removed. RESULTS: The greatest change in strength occurred during the
last 3 months, i.e., from the third to the sixth month following surgery (P <=
0.05). The average amount of urinary incontinence on the day of catheter removal
was approximately 311 g per 8 hr. Urinary incontinence decreased by 93.6% from
the day of catheter removal 6 months later. A strong correlation (P <= 0.001) of
reverse dependence was determined between pelvic floor muscle strength before
surgery and the amount of urinary incontinence 6 months following surgery.
CONCLUSION: The greatest change of pelvic floor muscles strength and endurance
occurred during the third to the sixth month following surgery. The greatest
change in urinary incontinence occurred during the first month following surgery.
Pelvic floor muscle strength causes a greater decrease in urinary incontinence
than endurance. The greater the pelvic floor muscle strength before surgery, the
lower the amount of urinary incontinence. Age also affects pelvic floor muscle
strength and endurance; this relation gradually weakens and with age disappears.
Neurourol. Urodynam. 36:126-131, 2017. (c) 2015 Wiley Periodicals, Inc.
PMID- 26421384
TI - Effect of breakfast omission on subjective appetite, metabolism, acylated ghrelin
and GLP-17-36 during rest and exercise.
AB - OBJECTIVES: Breakfast omission induces compensatory eating behaviour at lunch,
but often reduces daily energy intake. This study investigated the effect of
breakfast omission on within-day subjective appetite, energy expenditure,
substrate utilisation, and appetite hormone profiles, in response to standardised
feeding and exercise. METHODS: Eight male, habitual breakfast eaters completed
two randomised trials. Subjects arrived overnight fasted (0 h), and either
consumed (BC) or omitted (BO) a standardized breakfast (mean standard deviation
[SD]) (3085 [217] kJ). Lunch (4162 [510] kJ) and dinner (4914 [345] kJ) were
provided at 4.5 and 10 h, respectively and subjects performed 60 min fixed
intensity cycling (50% VO2 peak) at 8 h. Blood samples were collected at 0, 4.5,
6, and 8 h, with expired air and subjective appetite sensations (hunger,
fullness, desire to eat (DTE), and prospective food consumption [PFC]) collected
throughout. Heart rate and perceived exertion were measured during exercise.
RESULTS: Hunger, DTE and PFC were greater and fullness lower during BO (P < 0.05)
between breakfast and lunch, with no differences after lunch (P > 0.193). Resting
energy expenditure was greater at 2.5 h during BC (P < 0.05) with no other
differences between trials (P > 0.156). Active glucogon-like peptide-1 (GLP-17
36) was greater (P < 0.05) and acylated ghrelin tended to be greater (P = 0.078)
at 4.5 h during BC. Heart rate was greater on BO (P < 0.05) during exercise.
CONCLUSIONS: The results of this laboratory-controlled study suggest that the
effects of breakfast omission are transient and do not extend beyond lunch, even
when the negative energy balance created by breakfast omission is sustained via
standardised feeding and exercise.
PMID- 26421386
TI - Predicted versus measured resting energy expenditure in patients requiring home
parenteral nutrition.
PMID- 26421385
TI - omega-3 fatty acids as an adjuvant therapy ameliorates methotrexate-induced
hepatotoxicity in children and adolescents with acute lymphoblastic leukemia: A
randomized placebo-controlled study.
AB - OBJECTIVES: Methotrexate (MTX)-induced hepatotoxicity is a significant clinical
problem that may affect overall prognosis and disease outcome. Oxidative stress
is a key player in its pathogenesis. The aim of this study was to investigate the
role of omega-3 fatty acids as an adjuvant therapy in children and adolescents
with acute lymphoblastic leukemia (ALL) during the maintenance phase of
chemotherapy and the effect of omega-3 on MTX-induced hepatotoxicity. METHODS:
This randomized, double-blind, placebo-controlled trial included 70 patients with
ALL who were in the maintenance phase. The participants were divided into two
groups: group A received oral MTX and omega-3 fatty acids (1000 mg/d) and group B
(received MTX and placebo). Both groups were followed-up for 6 mo with assessment
of liver enzymes, total antioxidant capacity (TAC), uric acid, malondialdhyde,
superoxide dismutase (SOD), and glutathione peroxidase. The trial was registered
at ClinicalTrials.gov (NCT02373579). RESULTS: Baseline clinical and laboratory
parameters were consistent between the two groups (P > 0.05). After 6 mo, liver
enzymes and malondialdhyde increased, whereas TAC, uric acid, SOD, and
glutathione peroxidase decreased in group B (MTX and placebo) compared with
baseline levels or with group A ALL patients receiving omega-3 fatty acids (P <
0.001). The addition of omega-3 to MTX maintained normal liver function and
oxidant-antioxidant levels among group A patients at the end of treatment
compared with pretherapy levels (P > 0.05). No adverse reactions due to omega-3
supplementation were reported. ALT was inversely correlated to TAC and SOD in the
MTX group. CONCLUSIONS: The study determined that omega-3 fatty acids ameliorated
MTX-induced hepatotoxicity and could be safely used during the maintenance phase
of ALL.
PMID- 26421387
TI - Micronutrient deficiencies in early childhood can lower a country's GDP: The
Myanmar example.
AB - Myanmar (Burma) is a developing country in South East Asia. While Myanmar is
among the 20 countries where 80% of the world's malnourished children live, its
military consumes the majority of the national budget. Children who are
malnourished between conception and age two are at high risk for impaired
physical and mental development, which adversely affects the country's
productivity and growth. Myanmar is facing three major micronutrient deficiencies
which are iodine, iron and vitamin A deficiencies. The three micronutrient
deficiencies can cost about 2.4% of the country's GDP. Children are the future of
Myanmar and persistent micronutrient deficiencies will hamper its economic growth
and lower its GDP.
PMID- 26421389
TI - Interventional trials in atypical parkinsonism.
AB - Atypical parkinson disorders (APD) are rapidly progressive neurodegenerative
diseases with a variable clinical presentation that may even mimic Parkinson's
disease. Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and
corticobasal degeneration (CBD) are commonly summarized under this umbrella term.
Significant developments in research have expanded knowledge and have broadened
available symptomatic treatments, particularly for the treatment of neurogenic
orthostatic hypotension. Nonetheless, symptomatic support still remains limited
in all of these disorders. Currently, there exists no effective treatment to
delay disease progression and disease-modifying trials have failed to provide
coherent and convincing results. Recent trials of rasagiline (in MSA), rifampicin
(in MSA), tideglusib (in PSP) and davunetide (in PSP) reported negative results.
Nevertheless, large cohorts of patients were recruited for interventional studies
in the last few years which improved our understanding of trial methodology in
APDs immensely. In addition, remarkable progress in basic research has been
reported recently and will provide a solid foundation for future therapeutic
trials. In this review, we will summarize published randomized, placebo
controlled clinical trials (RCTs) in APDs. Additionally, the design of ongoing
and unpublished interventions will be presented.
PMID- 26421388
TI - Expression of inflammation-related miRNAs in white blood cells from subjects with
metabolic syndrome after 8 wk of following a Mediterranean diet-based weight loss
program.
AB - OBJECTIVES: The aim of this study was to evaluate the influence of a dietary
strategy for weight loss (the RESMENA [reduction of metabolic syndrome in
Navarra, Spain] diet) on the expression of inflammation-related microRNAS
(miRNAs) and genes in white blood cells (WBC) from individuals with metabolic
syndrome (MetS). METHODS: The clinical, anthropometric, and biochemical
characteristics of 40 individuals with MetS (20 men and 20 women; age: 48.84 +/-
10.02 y; body mass index: 35.41 +/- 4.42 kg/m(2)) were evaluated before and after
an 8-wk hypocaloric diet based on the Mediterranean dietary pattern. Nutrient
intake was assessed with a food frequency questionnaire and 48-h weighed food
records. Total RNA was isolated from WBC and the expression of some inflammation
related miRNAs and mRNAs (IL-6, TNF-alpha, ICAM-1, IL-18, SERPINE1, VCAM-1,
GAPDH) was assessed by quantitative polymerase chain reaction. RESULTS: The
RESMENA nutritional intervention improved most anthropometric and biochemical
features. The expression of miR-155-3p was decreased in WBC, whereas Let-7b was
strongly upregulated as a consequence of the dietary treatment. However, they
were not correlated with the expression of the proinflammatory genes in the same
cells. The changes in the expression of let-7b, miR-125b, miR-130a, miR-132-3p,
and miR-422b were significantly associated with changes in diet quality when
assessed by the Healthy Eating Index. Moreover, low consumption of lipids and
saturated fat (g/d) were associated with higher expression of let-7b after the
nutritional intervention. CONCLUSIONS: The Mediterranean-based nutritional
intervention was able to induce changes in the expression of let-7b and miR-155
3p in WBC from patients with MetS after 8 wk. Moreover, the quality of the diet
has an important effect on the miRNAs expression changes. These results should be
highlighted because these miRNAs have been associated with inflammatory gene
regulation and important human diseases.
PMID- 26421390
TI - Juvenile dystonia-parkinsonism syndrome caused by a novel p.S941Tfs1X ATP13A2
(PARK9) mutation.
PMID- 26421392
TI - The phenotypic spectrum of progressive supranuclear palsy.
AB - Traditionally, the clinical picture of progressive supranuclear palsy (PSP) was
defined by early postural instability with falls, supranuclear vertical gaze
palsy, symmetric akinesia and rigidity, frontal and subcortical dementia, and
pseudobulbar palsy, leading to death after a mean disease duration of
approximately six years. A definite diagnosis of PSP depends on neuropathological
confirmation. In recent years, clinico-pathological studies have drawn attention
to various "atypical" clinical manifestations of PSP. In these, a clinical
diagnosis of PSP is delayed or never accomplished. Comprehensive understanding of
the natural history of PSP is required to permit an early and accurate diagnosis.
Based on current evidence, this review provides an update on the clinical
spectrum of PSP.
PMID- 26421391
TI - Speech discrimination is impaired in parkinsonian patients: Expanding the
audiologic findings of Parkinson's disease.
AB - BACKGROUND AND OBJECTIVES: Hearing impairment (HI) has been previously
demonstrated in patients with Parkinson's disease (PD). Pure Tone Audiometry
(PTA) gives no information about patients' ability to hear and understand speech.
To find out hearing ability and speech discrimination of PD patients, we expanded
audiological evaluation by means of speech audiometry (SA). PATIENTS AND METHODS:
We screened a series of consecutive PD patients. Severity of motor symptoms and
staging were measured by the UPDRS-III and the H&Y scales. Audiometric evaluation
consisted of a standardized audiological examination, PTA and SA. Healthy age-
and sex-matched subjects were selected as controls. RESULTS: 45 PD patients and
45 healthy controls were enrolled. PTA confirmed our previous finding of high
frequency HI in PD patients. The mean values for the Speech Recognition Threshold
were higher in PD patients as compared with controls. PD patients were more
likely to have impaired speech discrimination profiles and higher disease stages.
Neither the patients nor the controls showed a significant speech-tone
dissociation and rollover phenomenon. CONCLUSION: Our results confirmed
sensorineural HI in PD patients. Moreover, SA showed impaired speech
discrimination abilities in PD patients as compared with control group thus
expanding the audiologic findings of PD.
PMID- 26421393
TI - Syndromic associations and RNF216 mutations.
PMID- 26421395
TI - Promoting the science and art of veterinary medicine.
PMID- 26421396
TI - A second glance at financial expectations of first-year veterinary students.
PMID- 26421397
TI - Understanding companion animal practitioners' attitudes toward antimicrobial
stewardship.
PMID- 26421398
TI - What Is Your Diagnosis? Dilated cardiomyopathy.
PMID- 26421399
TI - Theriogenology Question of the Month. Twins in an alpaca.
PMID- 26421400
TI - Pathology in Practice. Cerebellar coenurosis in a sheep.
PMID- 26421401
TI - Pathology in Practice. Dermatitis, cellulitis, and myositis caused by S
marcescens infection in a cat.
PMID- 26421402
TI - Injuries and illnesses among Federal Emergency Management Agency-certified search
and-recovery and search-and-rescue dogs deployed to Oso, Washington, following
the March 22, 2014, State Route 530 landslide.
AB - OBJECTIVE: To establish types and rates of injuries and illnesses among search
and-recovery and search-and-rescue dogs deployed to Oso, Wash, following the
March 22, 2014, State Route 530 landslide. DESIGN: Medical records review and
cross-sectional survey. ANIMALS: 25 Federal Emergency Management Agency-certified
search dogs. PROCEDURES: On-site medical records and postdeployment laboratory
test results were reviewed and an electronic survey was distributed to handlers
within 8 days after demobilization. RESULTS: Dogs worked a total of 244 search
shifts totaling 2,015 hours. Injuries and illnesses were reported in 21 (84%)
dogs. Wounds (abrasions, pad wear, paw pad splits, and lacerations) were the most
common injury, with an incidence rate of 28.3 wounds/1,000 hours worked.
Dehydration was the most common illness, with an incidence rate of 10.4 cases of
dehydration/1,000 hours worked. Total incidence rate for all health events was
66.5 events/1,000 hours worked. Two search dogs were removed from search
operations for 2 days because of health issues. All others continued search
operations while receiving treatment for their medical issues. All health issues
were resolved during the deployment or within 2 weeks after demobilization.
CONCLUSIONS AND CLINICAL RELEVANCE: Results revealed that search dogs deployed to
the Oso, Wash, landslide incurred injuries and illnesses similar to those
reported following other disasters (dehydration, wounding, vomiting, and
diarrhea) but also incurred medical issues not previously documented (acute
caudal myopathy, cutaneous mass ruptures, and fever). The reported medical issues
were minor; however, prompt veterinary care helped prevent them from developing
into more serious conditions.
PMID- 26421403
TI - Association between methicillin-resistant Staphylococcus pseudintermedius
carriage and the development of surgical site infections following tibial plateau
leveling osteotomy in dogs.
AB - OBJECTIVE: To evaluate the association between preoperative carriage of
methicillin-resistant Staphylococcus pseudintermedius (MRSP) and the development
of surgical site infections (SSIs) following tibial plateau leveling osteotomy
(TPLO) in dogs. DESIGN: Prospective multicenter study. ANIMALS: 549 dogs.
PROCEDURES: At 7 veterinary hospitals, swab specimens were obtained from the
pharynx, nares, rectum, and skin of dogs admitted for TPLO. Specimens were
submitted for culture of MRSP. For each dog, information regarding preoperative
and postoperative antimicrobial administration, comorbidities, contact with other
dogs, and whether the dog developed an SSI was obtained. Univariable and
multivariable analyses were performed to identify variables associated with
preoperative and postoperative MRSP colonization and the development of an SSI.
RESULTS: Of the 549 study dogs, 24 (4.4%) were identified as MRSP carriers before
TPLO and 37 (6.7%) developed an SSI after TPLO. Bacteriologic culture was
performed on specimens obtained from 32 of the 37 SSIs, and MRSP was isolated
from 11 (34%). Carriers of MRSP (OR, 6.72; 95% confidence interval [CI], 2.12 to
21.4) and Bulldogs (OR, 11.1; 95% CI, 2.07 to 59.3) were at risk for development
of an SSI after TPLO, whereas postoperative administration of antimicrobials (OR,
0.36; 95% CI, 0.15 to 0.91) appeared to protect against development of an SSI.
CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that carriage of MRSP were
a risk factor for development of an SSI after TPLO and measures to rapidly
identify and treat MRSP carriers are warranted. Postoperative administration of
antimicrobials protected against development of an SSI after TPLO.
PMID- 26421404
TI - Factors associated with pathological fractures in dogs with appendicular primary
bone neoplasia: 84 cases (2007-2013).
AB - OBJECTIVE: To determine the incidence of pathological fractures associated with
appendicular primary bone tumors in dogs managed medically and to identify
potential risk factors at the time of radiographic diagnosis that may be
associated with eventual pathological fracture. DESIGN: Retrospective case
series. ANIMALS: 84 dogs with primary long bone neoplasia treated medically.
PROCEDURES: Medical records for dogs with a diagnosis of primary long bone
neoplasia based on results of radiography that was confirmed subsequently at
necropsy were reviewed. Owners elected medical treatment at a pain clinic. Data
regarding clinical signs, diagnostic testing, pathological findings, and outcome
were evaluated. RESULTS: 84 dogs met study inclusion criteria with 85 limbs
affected. Osteosarcoma was the most common tumor and was identified in 78 of 85
(91.8%) limbs. The median time from diagnosis to euthanasia was 111 days (range,
28 to 447 days). Pathological fractures were identified in 33 of 85 limbs (38%),
with the femur most commonly affected, (8/14 [57.1%]), followed by the tibia
(9/17 [52.9%]), humerus (10/27 [37%]), radius (5/25 [20%]), and ulna (1/2 [50%]).
Logistic regression analysis indicated that tumors arising from long bones other
than the radius had odds of eventual fracture 5.05 as great as the odds for
tumors of the radius, and lytic tumors had odds of eventual fracture 3.22 as
great as the odds for tumors that appeared blastic or mixed lytic-blastic.
CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that radial primary bone
tumors were less likely and lytic tumors were more likely to fracture. The
overall incidence of pathological fractures secondary to appendicular primary
bone neoplasia in this study with patients treated by means of intensive
management for bone pain was higher than previously reported.
PMID- 26421405
TI - Subcutaneous ureteral bypass device for treatment of iatrogenic ureteral ligation
in a kitten.
AB - CASE DESCRIPTION: A 17-week-old spayed female Sphinx was evaluated after a 3-day
history of inappetence, lethargy, and vomiting. Three weeks prior, the kitten had
undergone routine elective ovariohysterectomy. CLINICAL FINDINGS: Abdominal
ultrasonography revealed moderate hydronephrosis of the left kidney, and the left
ureter was tortuous and dilated from the kidney to the level of the midureter,
where it abruptly tapered. No discrete cause of obstruction could be identified.
Clinicopathologic analyses revealed that the kitten was nonazotemic. TREATMENT
AND OUTCOME: Exploratory laparotomy revealed that the distal portion of the left
ureter was irregular with ill-defined margins and abundant scar tissue, likely
secondary to iatrogenic ureteral ligation during the ovariohysterectomy (suture
was not observed). Intraoperative antegrade pyelography confirmed complete left
ureteral obstruction extending distally from the level of the midureter. A
subcutaneous ureteral bypass device was placed to allow for renal decompression.
No complications were encountered in the perioperative period, and the kitten
recovered well after anesthesia. The kitten was discharged from the hospital 7
days after initial evaluation and continued to do well after surgery. At long
term follow-up, abdominal ultrasonography confirmed resolution of hydronephrosis
and ureteral dilation. CLINICAL RELEVANCE: A subcutaneous ureteral bypass device
successfully allowed renal decompression in a kitten with iatrogenic ureteral
ligation. A subcutaneous ureteral bypass device may be an alternative to
historical surgical options in cases of unilateral ureteral obstruction and may
result in a good long-term outcome.
PMID- 26421406
TI - Prevalence of and risk factors associated with ovine progressive pneumonia in
Wyoming sheep flocks.
AB - OBJECTIVE: To determine the prevalence of antibodies against small ruminant
lentivirus (SRLV), the causative agent of ovine progressive pneumonia (OPP), and
to identify risk factors associated with OPP in Wyoming sheep flocks. DESIGN:
Cross-sectional study. ANIMALS: 1,415 sheep from 54 flocks in Wyoming.
PROCEDURES: Flocks were surveyed as part of the National Animal Health Monitoring
System (NAHMS) 2011 sheep study. Serum samples obtained from sheep in Wyoming
were analyzed for anti-SRLV antibodies by use of a competitive-inhibition ELISA.
The prevalence of seropositive animals overall and within each flock was
calculated. Respective associations between flock OPP status and various
demographic and management variables were assessed. RESULTS: The estimated
prevalence of sheep seropositive for anti-SRLV antibodies and OPP-infected flocks
in Wyoming was 18.0% and 47.5%, respectively. Within OPP-infected flocks, the
prevalence of seropositive sheep ranged from 3.9% to 96%. Flocks maintained on
nonfenced range were more likely to be infected with OPP than were flocks
maintained on fenced range (OR, 3.4; 95% confidence interval, 1.1 to 10.7). The
estimated prevalence of OPP-infected flocks in Wyoming did not vary substantially
from that at the regional or national level reported in the NAHMS 2001 sheep
study. Compared with results of the NAHMS 2011 sheep study, Wyoming producers
were more familiar with OPP than were other US sheep producers, but only 61% of
Wyoming producers surveyed reported being very or somewhat familiar with the
disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that OPP is
prevalent in many Wyoming sheep flocks, which suggested that continued efforts
are necessary to increase producer knowledge about the disease and investigate
practices to minimize economic losses associated with OPP.
PMID- 26421407
TI - Opinions of clinical veterinarians at a US veterinary teaching hospital regarding
antimicrobial use and antimicrobial-resistant infections.
AB - OBJECTIVE: To determine opinions of faculty members with clinical appointments,
clinical veterinarians, residents, and interns at a US veterinary teaching
hospital regarding antimicrobial use and antimicrobial-resistant infections.
DESIGN: Cross-sectional survey. SAMPLE: 71 veterinarians. PROCEDURES: An online
questionnaire was sent to all veterinarians with clinical service
responsibilities at the North Carolina State University veterinary teaching
hospital (n = 167). The survey included 23 questions regarding demographic
information, educational experiences, current prescribing practices, and personal
opinions related to antimicrobial selection, antimicrobial use, restrictions on
antimicrobial use, and antimicrobial resistance. RESULTS: Of the 167
veterinarians eligible to participate, 71 (43%) responded. When respondents were
asked to rate their level of concern (very concerned = 1; not concerned = 5)
about antimicrobial-resistant infections, most (41/70 [59%]) assigned a score of
1, with mean score for all respondents being 1.5. Most survey participants rated
their immediate colleagues (mean score, 1.9) as more concerned than other
veterinary medical professionals (mean score, 2.3) and their clients (mean score,
3.4). Fifty-nine of 67 (88%) respondents felt that antimicrobials were
overprescribed at the hospital, and 32 of 69 (46%) respondents felt uncomfortable
prescribing at least one class of antimicrobials (eg, carbapenems or
glycopeptides) because of public health concerns. CONCLUSIONS AND CLINICAL
RELEVANCE: Findings indicated that veterinarians at this teaching hospital were
concerned about antimicrobial resistance, thought antimicrobials were
overprescribed, and supported restricting use of certain antimicrobial classes in
companion animals. Findings may be useful in educating future veterinarians and
altering prescribing habits and antimicrobial distribution systems in veterinary
hospitals.
PMID- 26421408
TI - Risk factors for suicide, attitudes toward mental illness, and practice-related
stressors among US veterinarians.
AB - OBJECTIVE: To evaluate the prevalence of suicide risk factors, attitudes toward
mental illness, and practice-related stressors among US veterinarians. DESIGN:
Cross-sectional survey. SAMPLE: 11,627 US veterinarians. PROCEDURES: Between July
1 and October 20, 2014, a Web-based questionnaire was made available through the
Veterinary Information Network (VIN), VIN News Service, JAVMA News, and email
messages to US veterinarians sent by a veterinary medical association,
agriculture or livestock department, or health department of each state (except
Maine) and Puerto Rico. RESULTS: Of 11,627 respondents, 3,628 (31%) were male.
Modal age category was 30 to 39 years, and modal range for years practicing
veterinary medicine was 10 to 19 years. There were 7,460 (64%) respondents who
primarily practiced small animal medicine, and 4,224 (36%) who were practice
owners. There were 1,077 (9%) respondents with current serious psychological
distress. Since leaving veterinary school, 3,655 (31%) respondents experienced
depressive episodes, 1,952 (17%) experienced suicidal ideation, and 157 (1%)
attempted suicide. Currently, 2,228 (19%) respondents were receiving treatment
for a mental health condition. Only 3,250 of 10,220 (32%) respondents somewhat or
strongly agreed that people are sympathetic toward persons with mental illness.
The most commonly reported practice-related stressor was demands of practice.
CONCLUSIONS AND CLINICAL RELEVANCE: In this survey, approximately 1 in 11
veterinarians had serious psychological distress and 1 in 6 experienced suicidal
ideation since leaving veterinary school. Implementing measures to help
veterinarians cope with practice-related stressors and reducing barriers
veterinarians face in seeking mental health treatment might reduce the risk for
suicide among veterinarians.
PMID- 26421409
TI - The efficacy of hydroxychloroquine in altering pregnancy outcome in women with
antiphospholipid antibodies. Evidence and clinical judgment.
AB - The use of low-dose aspirin and heparinoids has improved the pregnancy outcome in
obstetric antiphospholipid syndrome (APS). However, current treatment fails in 20
30% of APS pregnancies, raising the need to explore other treatments to improve
obstetrical outcome. Hydroxychloroquine (HCQ) is widely used in patients with
autoimmune diseases, mainly systemic lupus erythematous (SLE), due to its anti
inflammatory, anti-aggregant and immune-regulatory properties. Evidence from in
vitro and animal models suggests a potential protective effect of HCQ in
obstetric APS. Pending the availability of prospective trials, we aimed to
systematically review the available evidence and to assess the clinical judgment
of a panel of experts regarding the use of HCQ in improving pregnancy outcome in
women with antiphospholipid antibodies (aPL). Clinical data on the ability of HCQ
to improve pregnancy outcome in women with aPL are very limited in the available
literature. Only one cohort study evaluating maternal and fetal outcome of
pregnancy in patients with SLE who were exposed to HCQ was identified. Four of 14
(29%) treated with HCQ patients had pregnancy failure, compared with six of 24
(25%) of patients not treated with HCQ. However, the effect of HCQ was not
adjusted for the use of other medications such as aspirin, heparins or steroids.
Selected experts were contacted by e-mail and asked to review the summary of the
evidence provided by the working group and to briefly answer each of the proposed
questions. Overall, the panel of experts agreed that adding HCQ could be
considered in selected cases or after failure of standard treatment with aspirin
and a heparin agent. Specifically, the majority of experts considered adding HCQ
in specific scenarios, such as women with previous thrombosis (either arterial
and/or venous), and/or with previous ischaemic placenta-mediated complications.
Prospective studies are necessary before the use of HCQ during pregnancy in women
with aPL should be routinely recommended for clinical practice.
PMID- 26421410
TI - Nonmotor disabilities in patients with facial palsy measured by patient-reported
outcome measures.
AB - OBJECTIVES/HYPOTHESIS: To describe changes of motor and nonmotor disabilities in
patient with peripheral facial palsy (FP) during treatment using the patient
reported outcome measures (PROMs) Facial Clinimetric Evaluation (FaCE), Facial
Disability Index (FDI), and Short Form 36-Item Questionnaire (SF-36) and to
analyze predictors for these changes STUDY DESIGN: Prospective, single-center
longitudinal study. METHODS: One hundred twenty patients with FP underwent at
least two PROMs between 2012 and 2015. Predictors for changes of the PROMs were
analyzed univariately using Pearson's correlation and multivariately using linear
regression models. RESULTS: The mean interval between onset of FP to first
presentation was 29 +/- 64 months and between first and final assessment 8.7 +/-
7.2 months. Initial House-Brackmann grading was 4.0 +/- 1.3 and final House
Brackmann grading was 2.8 +/- 1.6 (P < .001). All mean FaCE and FDI but only some
SF-36 subscores improved over time (all P < .05). Adjuvant treatment was an
independent predictor for improvement of the FaCE Facial Comfort subscore (P =
.015) and a malignant tumor as primary disease for improvement of the FaCE Oral
Function subscore (P = .044). Unemployment was a predictor for improvement of the
FDI Social/Well-Being Function (P = .035). First assessment <90 days after onset
was a predictor for improvement of the SF-36 Bodily Pain subscore (P = .025), a
primary malignant disease for improvement of the SF-36 General Health perception
(P = .004), and idiopathic FP for improvement of the SF-36 Social Functioning
subscore (P = .017). CONCLUSIONS: Changes of motor function revealed by classical
grading systems mostly do not correlate with changes of nonmotor disabilities
during treatment of FP. Many other factors are associated with changes of PROMs
during the FP treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1516-1523, 2016.
PMID- 26421411
TI - A Quasi-Solid-State Sodium-Ion Capacitor with High Energy Density.
AB - A quasi-solid-state sodium-ion capacitor is demonstrated with nanoporous
disordered carbon and macroporous graphene as the negative and positive
electrodes, respectively, using a sodium-ion-conducting gel polymer electrolyte.
It can operate at a cell voltage as high as 4.2 V with an energy density of
record high 168 W h kg(-1).
PMID- 26421412
TI - Postoperative prognostic nutritional index change is an independent predictor of
survival in patients with small hepatocellular carcinoma.
AB - BACKGROUND: There is limited information concerning the postoperative prognostic
nutritional index change (DeltaPNI) in hepatocellular carcinoma (HCC). This study
was designed to evaluate the prognostic value of DeltaPNI in patients with small
HCC who underwent liver resection. METHODS: A retrospective cohort study was
performed to analyze 243 patients with small HCC who underwent liver resection.
Patients were divided into prognostic nutritional index (PNI)-increased group (n
= 161) and PNI-decreased group (n = 82) according to postoperative PNI change.
Clinical data, overall survival (OS), and recurrence-free survival (RFS) were
statistically compared between the 2 groups, and a multivariate analysis was used
to identify prognostic factors. RESULTS: Multivariable analysis revealed that
DeltaPNI as independent predictors of OS and RFS in patients with small HCC after
liver resection (P < .01 for both). CONCLUSIONS: Decreased PNI, but not low
preoperative PNI was an independent risk factor for OS and RFS in patients with
small HCC who underwent liver resection.
PMID- 26421413
TI - Complicated breast cancer-related lymphedema: evaluating health care resource
utilization and associated costs of management.
AB - BACKGROUND: Lymphedema can become a disabling condition necessitating inpatient
care. This study aimed to estimate complicated lymphedema incidence after breast
cancer surgery and calculate associated hospital resource utilization. METHODS:
We identified adult women undergoing lumpectomy and/or mastectomy with axillary
lymph node surgery between 2006 and 2012 using 5-state inpatient databases.
Patients were grouped according to the development of complicated lymphedema. The
primary outcomes were all-cause hospitalizations and health care charges within 2
years of surgery. Multivariate regression models were used to compare outcomes.
RESULTS: Of 56,075 women included, 2.3% had at least 1 hospital admission for
complicated lymphedema within 2 years of surgery. Despite confounder adjustment,
women with complicated lymphedema experienced 5 fold more all-cause (incidence
rate ratio = 5.02, 95% confidence interval: 4.76 to 5.29) admissions compared
with women without lymphedema. This resulted in substantially higher health care
charges ($58,088 vs $31,819 per patient, P < .001). Although axillary dissection
and certain comorbidities were associated with complicated lymphedema, breast
reconstruction appeared unrelated. CONCLUSIONS: Complicated lymphedema develops
in a quantifiable number of patients. The health care burden of lymphedema
underscored here mandates further investigation into targeted, anticipatory
management strategies for breast cancer-related lymphedema.
PMID- 26421414
TI - Elucidation of the binding mechanism of renin using a wide array of computational
techniques and biological assays.
AB - We investigate the binding mechanism in renin complexes, involving three drugs
(remikiren, zankiren and enalkiren) and one lead compound, which was selected
after screening the ZINC database. For this purpose, we used ab initio methods
(the effective fragment potential, the variational perturbation theory, the
energy decomposition analysis, the atoms-in-molecules), docking, molecular
dynamics, and the MM-PBSA method. A biological assay for the lead compound has
been performed to validate the theoretical findings. Importantly, binding free
energy calculations for the three drug complexes are within 3 kcal/mol of the
experimental values, thus further justifying our computational protocol, which
has been validated through previous studies on 11 drug-protein systems. The main
elements of the discovered mechanism are: (i) minor changes are induced to renin
upon drug binding, (ii) the three drugs form an extensive network of hydrogen
bonds with renin, whilst the lead compound presented diminished interactions,
(iii) ligand binding in all complexes is driven by favorable van der Waals
interactions and the nonpolar contribution to solvation, while the lead compound
is associated with diminished van der Waals interactions compared to the drug
bound forms of renin, and (iv) the environment (H2O/Na(+)) has a small effect on
the renin-remikiren interaction.
PMID- 26421415
TI - Profile of interferon-gamma response to latency-associated and novel in vivo
expressed antigens in a cohort of subjects recently exposed to Mycobacterium
tuberculosis.
AB - Recently some latency-associated antigens (LAA) of Mycobacterium tuberculosis
were described, as Rv2029c, Rv2031c, Rv2034, Rv2628 and Rv3353c. Of which, the
Rv2034 and Rv3353c also demonstrated in vivo expression. Therefore evaluating the
immune response to these antigens may help to understand their role in latent TB
infection. In a 1-year longitudinal study, IFN-gamma response by in vitro
peripheral blood mononuclear cells stimulation with LAA was investigated in
subjects recently exposed to TB, classified by IFN-gamma release assay (IGRA)
using RD1 antigens (ESAT-6:CFP-10) and tuberculin skin test (TST) response.
Except for Rv3353c, all the LAA triggered higher mean IFN-gamma response in IGRA
RD1(+) groups (p < 0.05). Combining the IFN-gamma-responders to Rv2029c, Rv2031c
plus Rv2034 detected 90.3% (28/31) of IGRA-RD1(+) and 66.7% (24/36) of TST(+)
contacts, while 95% (19/20) and 11% (2/17) were identified by classifying them
according to a TST and IGRA-RD1 double-positive or double-negative response,
respectively. In the follow-up, the TST convertors (negative to positive) also
demonstrated an IFN-gamma conversion to Rv2029c and Rv2031c, whereas the unique
TB incident case was exclusively detected via IGRA-Rv2029c and TST before
developing TB. A reversion rate to LAA (60%-100%) after prophylactic treatment
was observed at TST(+)/IGRA-RD1(+) group. Further studies into the performance of
these antigens are thus warranted.
PMID- 26421416
TI - Just What the Doctor Ordered: Using Parks to Improve Children's Health.
PMID- 26421417
TI - Spatiotemporally Controlled Reorganization of Signaling Complexes in the Plasma
Membrane of Living Cells.
AB - Triggered immobilization of proteins in the plasma membrane of living cells into
functional micropatterns is established by using an adaptor protein, which is
comprised of an antiGFP nanobody fused to the HaloTag protein. Efficient in situ
reorganization of the type I interferon receptor subunits as well as intact,
fully functional signaling complexes in living cells are achieved by this method.
PMID- 26421418
TI - Flavored Tobacco Product Use Among Middle and High School Students--United
States, 2014.
AB - The 2009 Family Smoking Prevention and Tobacco Control Act prohibits
"characterizing flavors" (e.g., candy, fruit, and chocolate) other than tobacco
and menthol in cigarettes; however, characterizing flavors are not currently
prohibited in other tobacco products. Analyses of retail sales data suggest that
U.S. consumption of flavored noncigarette tobacco products, including flavored
cigars and flavored e-cigarettes, has increased in recent years. There is growing
concern that widely marketed varieties of new and existing flavored tobacco
products might appeal to youths (2) and could be contributing to recent increases
in the use of tobacco products, including e-cigarettes and hookah, among youths.
CDC and the Food and Drug Administration (FDA) analyzed data from the 2014
National Youth Tobacco Survey (NYTS) to determine the prevalence of past 30 day
use (current use) of flavored e-cigarette, hookah tobacco, cigar, pipe tobacco or
smokeless tobacco products, and menthol cigarettes among middle and high school
students, and the proportion of current tobacco product users who have used
flavored products. An estimated 70.0% (3.26 million) of all current youth tobacco
users had used at least one flavored tobacco product in the past 30 days. Among
current users, 63.3%, (1.58 million) had used a flavored e-cigarette, 60.6%,
(1.02 million) had used flavored hookah tobacco, and 63.5% (910,000) had used a
flavored cigar in the past 30 days. Given the millions of current youth tobacco
users, it is important for comprehensive tobacco prevention and control
strategies to address all forms of tobacco use, including flavored tobacco
products, among U.S. youths.
PMID- 26421421
TI - Naringin Mitigates Cardiac Hypertrophy by Reducing Oxidative Stress and
Inactivating c-Jun Nuclear Kinase-1 Protein in Type I Diabetes.
AB - Cardiac hypertrophy (CH) in type 1 diabetes mellitus is attributed to increased
oxidative stress-associated activation of c-Jun Nuclear Kinase (JNK). We
investigated the effects of naringin on hyperglycemia-associated oxidative
stress, activation of JNK-1, and CH. Male Sprague-Dawley rats (225-250 g) (n = 7)
were divided into 6 groups. Groups I and II were orally treated with distilled
water [3.0 mL/kg body weight/day (BW)] and naringin (50 mg/kg BW), respectively.
Groups III-VI were rendered diabetic by a single intraperitoneal injection of 65
mg/kg BW of streptozotocin. Groups III, IV, and V were further treated with
insulin (4.0 I.U, s.c, twice daily), naringin (50 mg/kg BW), and ramipril (3.0
mg/kg BW), respectively. After 56 days, the animals were sacrificed and then
plasma and cardiac tissues obtained for further analysis. Naringin treatment of
diabetic rats significantly reversed oxidative stress, lipid peroxidation,
proteins oxidation, CH indices, and JNK protein activation compared with
untreated diabetic animals. Our results do suggest that naringin mitigates CH by
inhibiting oxidative stress leading to inactivation of JNK-1. Naringin
supplements could therefore ameliorate CH in diabetic patients.
PMID- 26421419
TI - Postoperative hepatitis B virus reactivation and surgery-induced
immunosuppression in patients with hepatitis B-related hepatocellular carcinoma.
AB - BACKGROUND: Hepatectomy in hepatocellular carcinoma (HCC) patients lead to
postoperative hepatitis B virus (HBV) reactivation (PHR) as well as
immunosuppression. METHODS: This prospective study involved 135 HBV-related HCC
patients and 42 control hepatic hemangioma patients. RESULTS: Among HCC patients,
26 (19.3%) suffered PHR. Risk factors for PHR were HBV-cAg S1 positivity [hazard
ratio (HR) = 404.82, P = 0.004], high preoperative total bilirubin level (HR =
186.38, P = 0.036), small preoperative proportions of CD3-CD16 + CD56 + cells (HR
= 0.01, P = 0.014) and CD19 + B cells (HR = 0.02, P = 0.016), blood transfusion
(HR = 157.03, P = 0.006) and high liver cirrhosis S score (HR = 270.45, P =
0.004). On postoperative day (POD) 3, PHR patients showed much greater
immunosuppression than non-PHR patients based on proportions of T cells (CD3+,
CD3 + CD4+, CD3 + CD8+), B cells (CD19+) and on levels of IgG, IgA antibodies,
complement proteins C3, and C4. By POD 7, PHR patients had partially recovered
but not as quickly as non-PHR patients: PHR patients still showed deficits in T
cells (CD3+, CD3 + CD4+), CD3-CD16 + CD56+ cells and in levels of IgM, C3, C4,
and C-reactive protein. CONCLUSION: PHR may be associated with resection-induced
immunosuppression in patients with HBV-related HCC.
PMID- 26421422
TI - Animal toxins and renal ion transport: Another dimension in tropical nephrology.
AB - Renal vascular and tubular ion channels and transporters involved in toxin injury
are reviewed. Vascular ion channels modulated by animal toxins, which result in
haemodynamic alterations and changes in blood pressure, include
ENaC/Degenerin/ASIC, ATP sensitive K channels (KATP ), Ca activated K channels
(Kca) and voltage gated Ca channels, mostly L-type. Renal tubular Na channels and
K channels are also targeted by animal toxins. NHE3 and ENaC are two important
targets. NCC and NKCC may be involved indirectly by vasoactive mediators induced
by inflammation. Most renal tubular K channels including voltage gated K channels
(Kv1), KATP , ROMK1, BK and SK are blocked by scorpion toxins. Few are inhibited
by bee, wasp and spider venoms. Due to small envenoming, incomplete block and
several compensatory mechanisms in renal tubules, serum electrolyte charges are
not apparent. Changes in serum electrolytes are observed in injury by large
amount of venom when several channels or transporters are targeted. Envenomings
by scorpions and bees are examples of toxins targeting multiple ion channels and
transporters.
PMID- 26421423
TI - WITHDRAWN: Metformin monotherapy for type 2 diabetes mellitus.
PMID- 26421424
TI - Glycerin laxatives for prevention or treatment of feeding intolerance in very low
birth weight infants.
AB - BACKGROUND: Feeding intolerance is a common clinical problem among preterm
infants. It may be an early sign of necrotising enterocolitis, sepsis or other
serious gastrointestinal conditions, or it may result from gut immaturity with
delayed passage of meconium. Glycerin laxatives stimulate passage of meconium by
acting as an osmotic dehydrating agent and increasing osmotic pressure in the
gut; they stimulate rectal contraction, potentially reducing the incidence of
feeding intolerance. OBJECTIVES: To assess the effectiveness and safety of
glycerin laxatives (enemas/suppositories) for prevention or treatment of feeding
intolerance in very low birth weight (VLBW) infants. SEARCH METHODS: We searched
the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 4),
MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature
(CINAHL). We restricted our search to all randomised controlled trials and
applied no language restrictions. We searched the references of identified
studies and reviews on this topic and handsearched for additional articles. We
searched the database maintained by the US National Institutes of Health
(www.clinicaltrials.gov) and European trial registries to identify ongoing
trials. SELECTION CRITERIA: We considered only randomised or quasi-randomised
controlled trials that enrolled preterm infants < 32 weeks' gestational age (GA)
and/or < 1500 g birth weight. We included trials if they administered glycerin
laxatives and measured at least one prespecified clinical outcome. DATA
COLLECTION AND ANALYSIS: We used standard methods of The Cochrane Collaboration
and its Neonatal Group to assess methodological quality of trials, to collect
data and to perform analyses. MAIN RESULTS: We identified three trials that
evaluated use of prophylactic glycerin laxatives in preterm infants. We
identified no trials that evaluated therapeutic use of glycerin laxatives for
feeding intolerance. Our review showed that prophylactic administration of
glycerin laxatives did not reduce the time required to achieve full enteral feeds
and did not influence secondary outcomes, including duration of hospital stay,
mortality and weight at discharge. Prophylactic administration of glycerin
laxatives resulted in failure of fewer infants to pass stool over the first 48
hours. Included trials reported no adverse events. AUTHORS' CONCLUSIONS: Our
review of available evidence for glycerin laxatives does not support the routine
use of prophylactic glycerin laxatives in clinical practice. Additional studies
are needed to confirm or refute the effectiveness and safety of glycerin
laxatives for prevention or treatment of feeding intolerance in VLBW infants.
PMID- 26421425
TI - Anticalins directed against the fibronectin extra domain B as diagnostic tracers
for glioblastomas.
AB - The standard of care for diagnosis and therapy monitoring of gliomas is magnetic
resonance imaging (MRI), which however, provides only an indirect and incomplete
representation of the tumor mass, offers limited information for patient
stratification according to WHO-grades and may insufficiently indicate tumor
relapse after antiangiogenic therapy. Anticalins are alternative binding proteins
obtained via combinatorial protein design from the human lipocalin scaffold that
offer novel diagnostic reagents for histology and imaging applications. Here, the
Anticalins N7A, N7E and N9B, which possess exquisite specificity and affinity for
oncofetal fibronectin carrying the extra domain B (ED-B), a well-known
proangiogenic extracellular matrix protein, were applied for immunohistochemical
studies. When investigating ED-B expression in biopsies from 41 patients with
confirmed gliomas of WHO grades I to IV, or in non-neoplastic brain samples, we
found that Anticalins specifically detect ED-B in primary glioblastoma multiforme
(GBM; WHO IV) but not in tumors of lower histopathological grade or in tumor-free
brain. In primary GBM samples, ED-B specific Anticalins locate to fibronectin
rich perivascular areas that are associated with angiogenesis. Anticalins
specifically detect ED-B both in fixed tumor specimen and on vital cells, as
evidenced by cytofluorometry. Beyond that, we labeled an Anticalin with the gamma
emitter (123) I and demonstrated specific binding to GBM-tissue samples using in
vitro autoradiography. Overall, our data indicate that ED-B specific Anticalins
are useful tools for the diagnosis of primary GBM and related angiogenic sites,
presenting them as promising tracers for molecular tumor imaging.
PMID- 26421426
TI - The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic
Colorectal Cancer.
AB - BACKGROUND: Tumoral heterogeneity is a major determinant of resistance in solid
tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions
within the whole body tumor load. This prospective multicentric proof-of-concept
study explores intra-individual metabolic response (mR) heterogeneity as a
treatment efficacy biomarker in chemorefractory metastatic colorectal cancer
(mCRC). METHODS: Standardized FDG-PET/CT was performed at baseline and after the
first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and
capecitabine (1700 mg/m2/day administered D1-14 every 21 days). MR assessment was
categorized according to the proportion of metabolically non-responding (non-mR)
lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable
lesions. RESULTS: Ninety-two patients were included. The median overall survival
(OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8-10.5) and
4.2 months (95% CI: 3.4-4.8) respectively. In the 79 assessable patients, early
PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with
at least one non-mR lesion in 32%, and a consistent non-mR or early disease
progression in 21%. On exploratory analysis, patients without any non-mR lesion
showed a significantly longer PFS (HR 0.34; 95% CI: 0.21-0.56, P-value <0.001)
and OS (HR 0.58; 95% CI: 0.36-0.92, P-value 0.02) compared to the other patients.
The proportion of non-mR lesions within the tumor load did not impact PFS/OS.
CONCLUSION: The presence of at least one metabolically refractory lesion is
associated with a poorer outcome in advanced mCRC patients treated with combined
sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may
represent an important predictive efficacy biomarker in mCRC. TRIAL REGISTRATION:
ClinicalTrials.gov NCT01290926.
PMID- 26421427
TI - Higher Lipoprotein (a) Levels Are Associated with Better Pulmonary Function in
Community-Dwelling Older People - Data from the Berlin Aging Study II.
AB - Reduced pulmonary function and elevated serum cholesterol levels are recognized
risk factors for cardiovascular disease. Currently, there is some controversy
concerning relationships between cholesterol, LDL-cholesterol, HDL-cholesterol,
serum triglycerides and lung function. However, most previous studies compared
patients suffering from chronic obstructive pulmonary disease (COPD) with healthy
controls, and only a small number examined this relationship in population-based
cohorts. Moreover, lipoprotein a [Lp(a)], another lipid parameter independently
associated with cardiovascular diseases, appears not to have been addressed at
all in studies of lung function at the population level. Here, we determined
relationships between lung function and several lipid parameters including Lp(a)
in 606 older community-dwelling participants (55.1% women, 68+/-4 years old) from
the Berlin Aging Study II (BASE-II). We found a significantly lower forced
expiration volume in 1 second (FEV1) in men with low Lp(a) concentrations (t
test). This finding was further substantiated by linear regression models
adjusting for known covariates, showing that these associations are statistically
significant in both men and women. According to the highest adjusted model, men
and women with Lp(a) levels below the 20th percentile had 217.3ml and 124.2ml
less FEV1 and 239.0ml and 135.2ml less FVC, respectively, compared to
participants with higher Lp(a) levels. The adjusted models also suggest that the
known strong correlation between pro-inflammatory parameters and lung function
has only a marginal impact on the Lp(a)-pulmonary function association. Our
results do not support the hypothesis that higher Lp(a) levels are responsible
for the increased CVD risk in people with reduced lung function, at least not in
the group of community-dwelling older people studied here.
PMID- 26421428
TI - Clinical Considerations of Preimplantation Genetic Diagnosis for Monogenic
Diseases.
AB - PURPOSE: The aim of this study was to explore factors contribute to the success
of PGD cycles for monogenic diseases. METHODS: During a 3-year period (January
2009 to December 2012), 184 consecutive ICSI-PGD cycles for monogenic diseases
reaching the ovum pick-up and fresh embryo-transfer stage performed at the
Reproductive Medicine Center of The First Affiliated Hospital Of Sun Yat-sen
University were evaluated. RESULTS: ICSI was performed on 2206 metaphase II
oocytes, and normal fertilization and cleavage rates were 83.4% (1840/2206) and
96.2% (1770/1840), respectively. In the present study, 60.5% (181/299) of day 3
good-quality embryos developed into good-quality embryos on day 4 after biopsy.
Collectively, 42.9% clinical pregnancy rate (79/184) and 28.5% implantation rate
(111/389) were presented. In the adjusted linear regression model, the only two
significant factors affecting the number of genetically unaffected embryos were
the number of biopsied embryos (coefficient: 0.390, 95%CI 0.317-0.463, P = 0.000)
and basal FSH level (coefficient: 0.198, 95%CI 0.031-0.365, P = 0.021). In the
adjusted binary logistic regression model, the only two significant factors
affecting pregnancy outcome were the number of genetically available transferable
embryos after PGD (adjusted OR 1.345, 95% CI 1.148-1.575, P = 0.000) and number
of oocyte retrieved (adjusted OR 0.934, 95% CI 0.877-0.994, P = 0.031).
CONCLUSION: There should be at least four biopsied embryos to obtain at least one
unaffected embryos in a PGD system for patients with single gene disorder and
under the condition of basal FSH level smaller than 8.0mmol/L. Moreover, if only
a low number (< 4) of biopsied embryos are available on day 3, the chance of
unaffected embryos for transfer was small, with poor outcome.
PMID- 26421429
TI - Non-Linear Characterisation of Cerebral Pressure-Flow Dynamics in Humans.
AB - Cerebral metabolism is critically dependent on the regulation of cerebral blood
flow (CBF), so it would be expected that vascular mechanisms that play a critical
role in CBF regulation would be tightly conserved across individuals. However,
the relationships between blood pressure (BP) and cerebral blood velocity
fluctuations exhibit inter-individual variations consistent with heterogeneity in
the integrity of CBF regulating systems. Here we sought to determine the nature
and consistency of dynamic cerebral autoregulation (dCA) during the application
of oscillatory lower body negative pressure (OLBNP). In 18 volunteers we recorded
BP and middle cerebral artery blood flow velocity (MCAv) and examined the
relationships between BP and MCAv fluctuations during 0.03, 0.05 and 0.07Hz
OLBNP. dCA was characterised using project pursuit regression (PPR) and locally
weighted scatterplot smoother (LOWESS) plots. Additionally, we proposed a
piecewise regression method to statistically determine the presence of a dCA
curve, which was defined as the presence of a restricted autoregulatory plateau
shouldered by pressure-passive regions. Results show that LOWESS has similar
explanatory power to that of PPR. However, we observed heterogeneous patterns of
dynamic BP-MCAv relations with few individuals demonstrating clear evidence of a
dCA central plateau. Thus, although BP explains a significant proportion of
variance, dCA does not manifest as any single characteristic BP-MCAv function.
PMID- 26421430
TI - Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and
Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma.
AB - BACKGROUND & AIMS: We evaluated the relationship between the early clinical
response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor
response in patients with advanced hepatocellular carcinoma. METHODS: Fifty-seven
patients who had intrahepatic hypervascular hepatocellular carcinoma and Child
Pugh (CP) class A disease at baseline were enrolled in this prospective,
multicenter, observational, non-interventional study. As an early clinical
response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on
contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels,
and remnant liver function were investigated. RESULTS: After 2 weeks of sorafenib
therapy, there were 26 patients (45.6%) without disappearance of arterial tumor
enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven
patients (12.3%) with two or more increments in the CP score. Multivariate
analysis showed that the absence of disappearance of arterial tumor enhancement
on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2
weeks of sorafenib therapy were significant and independent predictors of worse
survival. Upon scoring these three variables as "poor prognostic factors",
patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse
outcomes and a significantly higher progressive disease (PD) rate based on
modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib
therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall
survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p =
0.0003, respectively). CONCLUSIONS: Changes in intra-tumor blood flow on CE-CT,
AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be
useful for predicting the outcomes and anti-tumor response to sorafenib in
patients with advanced hepatocellular carcinoma.
PMID- 26421431
TI - Angiogenic Factors and Doppler Evaluation in Normally Growing Fetuses at Routine
Third-Trimester Scan: Prediction of Subsequent Low Birth Weight.
AB - OBJECTIVE: To evaluate in normally growing fetuses at routine 32-36 weeks scan
the performance of maternal angiogenic factors, Doppler and ultrasound indices in
predicting smallness for gestational age (SGA) at birth. METHODS: A cohort of
1,000 singleton pregnancies with normal estimated fetal weight (EFW, >=10th
centile) at 32-36 weeks scan was included. At inclusion, Doppler indices (mean
uterine artery pulsatility index [mUtA-PI], cerebroplacental ratio and normalized
umbilical vein blood flow by EFW (ml/min/kg) were evaluated, and blood samples
were collected and frozen. Nested in this cohort, maternal circulating placental
growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed
by enzyme-linked immunosorbent assay in all cases with a birth weight <10th
centile by customized standards and in an equivalent number of controls (birth
weight >=10th centile). RESULTS: 160 cases were included (80 SGA and 80
controls). EFW (2,128 vs. 2,279 g, p < 0.001), mUtA-PI z-values (-0.25 vs. -0.65,
p = 0.034) and sFlt-1/PlGF ratio (11.10 vs. 6.74, p < 0.005) were lower in SGA.
The combination of sFlt-1/PlGF ratio and EFW resulted in a 66.3% detection rate
for subsequent SGA, with 20% of false-positives. Fetal Doppler indices were not
predictive of SGA. CONCLUSIONS: In normally growing fetuses, maternal angiogenic
factors add to ultrasound parameters in predicting subsequent SGA at birth. This
supports further research to investigate composite scores in order to improve the
definition and identification of fetal growth restriction.
PMID- 26421432
TI - An Extremely Peramorphic Newt (Urodela: Salamandridae: Pleurodelini) from the
Latest Oligocene of Germany, and a New Phylogenetic Analysis of Extant and
Extinct Salamandrids.
AB - We describe an Oligocene newt specimen from western Germany that has gone
practically unnoticed in the literature despite having been housed in the Museum
fur Naturkunde (Berlin) for a century. It is referable to the coeval Chelotriton,
but is unusually peramorphic; for many characters it is more peramorphic than all
other caudates or even all other lissamphibians. Most noticeable are the position
of the jaw joints far caudal to the occiput, the honeycombed sculpture on the
maxilla, and the possible presence of a septomaxilla (which would be unique among
salamandrids). Referral to a species would require a revision of the genus, but
the specimen likely does not belong to the type species. A phylogenetic analysis
of nonmolecular characters of Salamandridae, far larger than all predecessors,
confirms the referral to Chelotriton. It further loosely associates the Oligocene
Archaeotriton and the Miocene Carpathotriton with the extant Lissotriton, though
the former may alternatively lie outside Pleurodelinae altogether. The Miocene?
I. randeckensis may not belong to the extant Ichthyosaura. The Miocene "Triturus"
roehrsi is found neither with the extant Ommatotriton nor with Lissotriton, but
inside an Asian/aquatic clade or, when geographic distribution is included as a
character, as the sister-group to all other European molgins. The main cause for
discrepancies between the results and the molecular consensus is not
heterochrony, but adaptations to a life in mountain streams; this is the most
likely reason why the Paleocene Koalliella from western Europe forms the sister
group to some or all of the most aquatic extant newts in different analyses. We
would like to urge neontologists working on salamandrids to pay renewed attention
to the skeleton, not limited to the skull, as a source of diagnostic and
phylogenetically informative characters.
PMID- 26421433
TI - A Conservation-Based Approach to Compensation for Livestock Depredation: The
Florida Panther Case Study.
AB - Calf (Bos taurus) depredation by the federally endangered Florida panther (Puma
concolor coryi) on ranches in southwest Florida is an important issue because
ranches represent mixed landscapes that provide habitat critical to panther
recovery. The objectives of this study were to (1) quantify calf depredation by
panthers on two ranches in southwest Florida, and (2) develop a habitat
suitability model to evaluate the quality of panther hunting habitat on
ranchlands, assess whether the model could predict predation risk to calves, and
discuss its potential to be incorporated into an incentive-based compensation
program. We ear-tagged 409 calves with VHF transmitters on two ranches during
2011-2013 to document calf mortality. We developed a model to evaluate the
quality of panther hunting habitat on private lands in southwest Florida using
environmental variables obtained from the Florida Natural Areas Inventory (FNAI)
Cooperative Landcover Database and nocturnal GPS locations of panthers provided
by the Florida Fish and Wildlife Conservation Commission (FWC). We then tested
whether the model could predict the location of calf depredation sites. Tagged
calf loss to panthers varied between the two ranches (0.5%/yr to 5.3%/yr) and may
have been influenced by the amount of panther hunting habitat on each ranch as
the ranch that experienced higher depredation rates contained a significantly
higher probability of panther presence. Depredation sites of tagged calves had a
significantly greater probability of panther presence than depredation sites of
untagged calves that were found by ranchers in open pastures. This suggests that
there may be more calves killed in high risk environments than are being found
and reported by ranchers and that panthers can hunt effectively in open
environments. It also suggests that the model may provide a means for evaluating
the quality of panther hunting habitat and the corresponding risk of depredation
to livestock across the landscape. We suggest that our approach could be applied
to prioritize and categorize private lands for participation in a Payment for
Ecosystem Services program that compensates landowners for livestock loss and
incentivizes conserving high quality habitat for large carnivores where livestock
depredation is a concern.
PMID- 26421434
TI - Hormetic Effect of Berberine Attenuates the Anticancer Activity of
Chemotherapeutic Agents.
AB - Hormesis is a phenomenon of biphasic dose response characterized by exhibiting
stimulatory or beneficial effects at low doses and inhibitory or toxic effects at
high doses. Increasing numbers of chemicals of various types have been shown to
induce apparent hormetic effect on cancer cells. However, the underlying
significance and mechanisms remain to be elucidated. Berberine, one of the major
active components of Rhizoma coptidis, has been manifested with notable
anticancer activities. This study aims to investigate the hormetic effect of
berberine and its influence on the anticancer activities of chemotherapeutic
agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 MUM)
promoted cell proliferation to 112% ~170% of the untreated control in various
cancer cells, while berberine at high dose rage (10 ~ 80 MUM) inhibited cell
proliferation. Further, we observed that co-treatment with low dose berberine
could significantly attenuate the anticancer activity of chemotherapeutic agents,
including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX). The
hormetic effect and thereby the attenuated anticancer activity of
chemotherapeutic drugs by berberine may attributable to the activated protective
stress response in cancer cells triggered by berberine, as evidenced by up
regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided
important information to understand the potential side effects of hormesis, and
suggested cautious application of natural compounds and relevant herbs in
adjuvant treatment of cancer.
PMID- 26421435
TI - The Influence of Infective Dose on the Virulence of a Generalist Pathogen in
Rainbow Trout (Oncorhynchus mykiss) and Zebra Fish (Danio rerio).
AB - Pathogen density and genetic diversity fluctuate in the outside-host environment
during and between epidemics, affecting disease emergence and the severity and
probability of infections. Although the importance of these factors for pathogen
virulence and infection probability has been acknowledged, their interactive
effects are not well understood. We studied how an infective dose in an
environmentally transmitted opportunistic fish pathogen, Flavobacterium
columnare, affects its virulence both in rainbow trout, which are frequently
infected at fish farms, and in zebra fish, a host that is not naturally infected
by F. columnare. We used previously isolated strains of confirmed high and low
virulence in a single infection and in a co-infection. Infection success
(measured as host morbidity) correlated positively with dose when the hosts were
exposed to the high-virulence strain, but no response for the dose increase was
found when the hosts were exposed to the low-virulence strain. Interestingly, the
co-infection resulted in poorer infection success than the single infection with
the high-virulence strain. The rainbow trout were more susceptible to the
infection than the zebra fish but, in both species, the effects of the doses and
the strains were qualitatively similar. We suggest that as an increase in dose
can lead to increased host morbidity, both the interstrain interactions and
differences in infectivity in different hosts may influence the severity and
consequently the evolution of disease. Our results also confirm that the zebra
fish is a good laboratory model to study F. columnare infection.
PMID- 26421436
TI - Local Pain Dynamics during Constant Exhaustive Exercise.
AB - The purpose of this study was to delineate the topological dynamics of pain and
discomfort during constant exercise performed until volitional exhaustion. Eleven
physical education students were tested while cycling and running at a "hard"
intensity level (e.g., corresponding to Borg's RPE (6-20) = 15). During the
tests, participants reported their discomfort and pain on a body map every 15s.
"Time on task" for each participant was divided into five equal non-overlapping
temporal windows within which their ratings were considered for analysis. The
analyses revealed that the number of body locations with perceived pain and
discomfort increased throughout the five temporal windows until reaching the mean
(+/- SE) values of 4.2 +/- 0.7 and 4.1 +/- 0.6 in cycling and running,
respectively. The dominant locations included the quadriceps and hamstrings
during cycling and quadriceps and chest during running. In conclusion, pain
seemed to spread throughout the body during constant cycling and running
performed up to volitional exhaustion with differences between cycling and
running in the upper body but not in the lower body dynamics.
PMID- 26421437
TI - Sputtering Yields for Mixtures of Organic Materials Using Argon Gas Cluster Ions.
AB - The sputtering yield volumes of binary mixtures of Irganox 1010 with either
Irganox 1098 or Fmoc-pentafluoro-L-phenylalanine (FMOC) have been measured for 5
keV Ar2000(+) ions incident at 45 degrees to the surface normal. The sputtering
yields are determined from the doses to sputter through various compositions of
100 nm thick, intimately mixed, layers. Because of matrix effects, the profiles
for secondary ions are distorted, and profile shifts in depth of 15 nm are
observed leading to errors above 20% in the deduced sputtering yield. Secondary
ions are selected to avoid this. The sputtering yield volumes for the mixtures
are shown to be lower than those deduced from a linear interpolation from the
pure materials. This is shown to be consistent with a simple model involving the
changing energy absorbed for the sputtering of intimate mixtures. Evidence to
support this comes from the secondary ion data for pairs of the different
molecules. Both binary mixtures behave similarly, but matrix effects are stronger
for the Irganox 1010/FMOC system.
PMID- 26421438
TI - EPR Distance Measurements in Native Proteins with Genetically Encoded Spin
Labels.
AB - The genetic encoding of nitroxide amino acids in combination with electron
paramagnetic resonance (EPR) distance measurements enables precise structural
studies of native proteins, i.e. without the need for mutations to create unique
reactive sites for chemical labeling and thus with minimal structural
perturbation. We here report on in vitro DEER measurements in native E. coli
thioredoxin (TRX) that establish the nitroxide amino acid SLK-1 as a
spectroscopic probe that reports distances and conformational flexibilities in
the enzyme with nonmutated catalytic centers that are not accessible by the use
of the traditional methanethiosulfonate spin label (MTSSL). We generated a
rotamer library for SLK-1 that in combination with molecular dynamics (MD)
simulation enables predictions of distance distributions between two SLK-1 labels
incorporated into a target protein. Toward a routine use of SLK-1 for EPR
distance measurements in proteins and the advancement of the approach to
intracellular environments, we study the stability of SLK-1 in E. coli cultures
and lysates and establish guidelines for protein expression and purification that
offer maximal nitroxide stability. These advancements and insights provide new
perspectives for facile structural studies of native, endogenous proteins by EPR
distance measurements.
PMID- 26421439
TI - A Journey toward Sulfolane Microemulsions Suggested as Inert, Nonaqueous Reaction
Media.
AB - Recently, it turned out that nanostructured reaction media containing highly
inert solvents as tetrahydrothiophen-1,1-dioxide (sulfolane) are beneficial for
strongly oxidizing or reductive reactions. Because of their ability of
solubilizing polar and nonpolar solvents with a large nanostructured interface in
particular microemulsions provide such interesting reaction media. Starting from
the pseudoternary microemulsion H2O-n-octane-C12E4/C12E5 (polyoxyethylene n-alkyl
ether), water was successively replaced by the highly inert tetrahydrothiophen
1,1-dioxide (sulfolane). We found that an increasing sulfolane content drives the
system beyond the tricritical point. Replacing the already long chain surfactants
C12E4 and C12E5 by a mixture of the even longer chain surfactants C18E6 and
C18E8, we were able to prepare nonaqueous sulfolane microemulsions for the first
time. We also teach how in a second step the phase behavior of the hydrophilic
sulfolane-n-octane-C18E8 system can be tuned at constant temperature (as required
by the reaction conditions) by addition of the hydrophobic cosurfactant 1-octanol
(C8E0). The change in curvature that occurs by adding 1-octanol is demonstrated
measuring the size of reverse micelles by DLS. We found that the radius varies
from at least 8 to 16 nm, a suitable sizes for inverse nanoreaction vessels.
PMID- 26421440
TI - The combination of gold nanorods and nanoparticles with DNA nanodevices for logic
gates construction.
AB - In this work, two DNA nanodevices were constructed utilizing a DNA strand
displacement reaction. With the assistance of gold nanoparticles (AuNPs) and gold
nanorods (AuNRs), the autonomous reactions can be reflected from the aggregation
states of nanoparticles. By sequence design and the two non-overlapping double
hump-like UV-vis spectral peaks of AuNPs and AuNRs, two logic gates with multiple
inputs and outputs were successfully run with expected outcomes. This method not
only shows how to achieve computing with multiple logic calculations but also has
great potential for multiple targets detection.
PMID- 26421441
TI - Crystallographic Characterization of II-VI Semiconducting Nanostructures via
Optical Second Harmonic Generation.
AB - We demonstrate the utility of optical second harmonic generation (SHG)
polarimetry to perform structural characterization of noncentrosymmetric, single
crystalline II-VI semiconducting nanowires, nanobelts, and nanoflakes. By
analyzing anisotropic SHG polarimetric patterns, we distinguish between wurtzite
and zincblende II-VI semiconducting crystal structures and determine their growth
orientation. The crystallography of these nanostructures was then confirmed via
transmission electron microscopy measurements performed on the same system. In
addition, we show that some intrinsic material properties such as nonlinear
coefficients and geometry-dependent optical in-coupling coefficients can also be
determined from the SHG experiments in WZ nanobelts. The ability to perform SHG
based structural characterization and crystallographic study of II-VI
semiconducting single-crystalline nanomaterials will be useful to correlate
structure-property relationships of nanodevices on which transmission electron
microscopy measurements cannot be typically performed.
PMID- 26421442
TI - Coordinate Activation of Redox-Dependent ASK1/TGF-beta Signaling by a
Multiprotein Complex (MPK38, ASK1, SMADs, ZPR9, and TRX) Improves Glucose and
Lipid Metabolism in Mice.
AB - AIMS: To explore the molecular connections between redox-dependent apoptosis
signal-regulating kinase 1 (ASK1) and transforming growth factor-beta (TGF-beta)
signaling pathways and to examine the physiological processes in which
coordinated regulation of these two signaling pathways plays a critical role.
RESULTS: We provide evidence that the ASK1 and TGF-beta signaling pathways are
interconnected by a multiprotein complex harboring murine protein serine
threonine kinase 38 (MPK38), ASK1, Sma- and Mad-related proteins (SMADs), zinc
finger-like protein 9 (ZPR9), and thioredoxin (TRX) and demonstrate that the
activation of either ASK1 or TGF-beta activity is sufficient to activate both the
redox-dependent ASK1 and TGF-beta signaling pathways. Physiologically, the
restoration of the downregulated activation levels of ASK1 and TGF-beta signaling
in genetically and diet-induced obese mice by adenoviral delivery of SMAD3 or
ZPR9 results in the amelioration of adiposity, hyperglycemia, hyperlipidemia, and
impaired ketogenesis. INNOVATION AND CONCLUSION: Our data suggest that the
multiprotein complex linking ASK1 and TGF-beta signaling pathways may be a
potential target for redox-mediated metabolic complications.
PMID- 26421443
TI - alpha-Quaternary Proline Derivatives by Intramolecular Diastereoselective
Arylation of N-Carboxamido Proline Ester Enolates.
AB - Pyrrolidine-2-carboxylate esters substituted in the 3-, 4- or 5-positions were
converted to their N'-aryl urea derivatives. Deprotonation at the 2-position to
form a potassium enolate led to migration of the N'-aryl substituent to the 2
position of the pyrrolidine ring, followed by cyclization of the resulting urea
to give bicyclic alpha-aryl hydantoin derivatives of substituted prolines.
Depending on the substitution pattern of the starting material, high
diastereoselectivity was observed in the aryl migration, allowing formation of
the products in enantiomerically enriched form, despite the intermediacy of a
planar enolate. The hydrolysis of the bicyclic hydantoins under basic conditions
gave a range of enantiopure and enantioenriched quaternary alpha-aryl proline
derivatives.
PMID- 26421444
TI - Examining the Process of Responding to Circumplex Scales of Interpersonal Values
Items: Should Ideal Point Scoring Methods Be Considered?
AB - The Circumplex Scales of Interpersonal Values (CSIV) is a 64-item self-report
measure of goals from each octant of the interpersonal circumplex. We used item
response theory methods to compare whether dominance models or ideal point models
best described how people respond to CSIV items. Specifically, we fit a
polytomous dominance model called the generalized partial credit model and an
ideal point model of similar complexity called the generalized graded unfolding
model to the responses of 1,893 college students. The results of both graphical
comparisons of item characteristic curves and statistical comparisons of model
fit suggested that an ideal point model best describes the process of responding
to CSIV items. The different models produced different rank orderings of high
scoring respondents, but overall the models did not differ in their prediction of
criterion variables (agentic and communal interpersonal traits and implicit
motives).
PMID- 26421445
TI - The impact of intrauterine infection on fetal brain damage assessed by S100B
protein concentrations in umbilical cord arteries.
AB - OBJECTIVE: To assess the impact of intrauterine infection on fetal brain damage
by measuring S100B protein concentration in umbilical cord arteries. METHODS: In
the intrauterine infection cases determined by pathology of 25 deliveries (Group
I) and non-infection cases of 35 deliveries as control (Group C), we compared
gestational age at delivery, birth weight, fetal heart rate monitoring during
labor, Apgar score, umbilical cord artery pH and S100B protein concentrations in
umbilical arteries measured by two-site immunoradiometric assay kit. RESULTS: (1)
There was no significant correlation between pH and concentration of S100B
protein. (2) Gestational age at delivery was found to be earlier in Group I,
resulting in lower birth weights, when compared with Group C. (3) There was no
significant difference between two groups concerning Apgar scores, pH. (4) S100B
protein concentrations in Group I was significantly higher than those of Group C
(3.9 7 +/- 0.66 versus 1.8 9 +/- 0.56 MUg/L, p < 0.05). (5) The concentration of
S100B protein in severe chorioamnionitis (CAM) cases were significantly higher
than those of mild CAM and control cases. CONCLUSION: Higher concentration of
S100B protein in Group I suggests that intrauterine infection itself has a
serious risk factor on fetal brain damage.
PMID- 26421446
TI - The use and safety of medications known to affect driving in Jordan: A cross
sectional study.
AB - OBJECTIVES: The aim of this study was to estimate the main driving-impairing
medications used by drivers in Jordan, the reported frequency of medication side
effects, the frequency of motor vehicle crashes (MVCs) while using driving
impairing medicines, as well as factors associated with MVCs. METHODS: A cross
sectional study involving 1,049 individuals (age 18-75 years) who are actively
driving vehicles and taking at least one medication known to affect driving
(anxiolytics, antidepressants, hypnotics, antiepileptics, opioids, sedating
antihistamines, hypoglycemic agents, antihypertensives, central nervous system
[CNS] stimulants, and herbals with CNS-related effects) was conducted in Amman,
Jordan, over a period of 8 months (September 2013-May 2014) using a structured
validated questionnaire. RESULTS: Sixty-three percent of participants noticed a
link between a medicine taken and feeling sleepy and 57% stated that they
experience at least one adverse effect other than sleepiness from their
medication. About 22% of the participants reported having a MVC while on
medication. Multiple logistic regression analysis showed that among the
participants who reported having a crash while taking a driving-impairing
medication, the odds ratios were significantly higher for the use of inhalant
substance (odds ratio [OR] = 2.787, P = .014), having chronic conditions (OR =
1.869, P = .001), and use of antiepileptic medications (OR = 2.348, P = .008) and
significantly lower for the use of antihypertensives (OR = 0.533, P = .008).
CONCLUSION: The study results show high prevalence of adverse effects of
medications with potential for driving impairment, including involvement in MVCs.
Our findings highlight the types of patient-related and medication-related
factors associated with MVCs in Jordan, such as inhalant use, presence of chronic
conditions, and use of antiepileptics.
PMID- 26421447
TI - The Stimulatory Effect of Notochordal Cell-Conditioned Medium in a Nucleus
Pulposus Explant Culture.
AB - OBJECTIVES: Notochordal cell-conditioned medium (NCCM) has previously shown to
have a stimulatory effect on nucleus pulposus cells (NPCs) and bone marrow
stromal cells (BMSCs) in alginate and pellet cultures. These culture methods
provide a different environment than the nucleus pulposus (NP) tissue, in which
the NCCM ultimately should exert its effect. The objective of this study is to
test whether NCCM stimulates NPCs within their native environment, and whether
combined stimulation with NCCM and addition of BMSCs has a synergistic effect on
extracellular matrix production. METHODS: Bovine NP tissue was cultured in an
artificial annulus in base medium (BM), porcine NCCM, or BM supplemented with 1
MUg/mL Link N. Furthermore, BM and NCCM samples were injected with 10(6) BMSCs
per NP sample. Samples were cultured for 4 weeks, and analyzed for biochemical
contents (water, glycosaminoglycan [GAG], hydroxyproline, and DNA), gene
expression (COL1A1, COL2A1, ACAN, and SOX9), and histology by Safranin O/Fast
Green staining. RESULTS: Culture in NCCM resulted in increased proteoglycan
content compared to day 0 and BM, similar to Link N. However, only minor
differences in gene expression compared to day 0 were observed. Addition of BMSCs
did not result in increased GAG content, and surprisingly, DNA content in BMSC
injected groups was not higher than in the other groups after 4 weeks of culture.
DISCUSSION: This study shows that, indeed, NCCM is capable of stimulating NPC
matrix production within the NP environment. The lack of increased DNA content in
the BMSC-injected groups indicates that BMSCs have died over time. Identification
of the bioactive factors in NCCM is crucial for further development of an NCCM
based treatment for intervertebral disc regeneration.
PMID- 26421448
TI - The Influence of Social and Nonsocial Variables on the Simon Effect.
AB - Recently, the Simon effect (SE) has been observed in social contexts when two
individuals share a two-choice task. This joint SE (JSE) has been interpreted as
evidence that people co-represent their actions. However, it is still not clear
if the JSE is driven by social factors or low-level mechanisms. To address this
question, we applied a common paradigm to a joint Simon task (Experiments 1 and
4), a standard Simon task (Experiment 2), and a go/no-go task (Experiment 3). The
results showed that both the JSE and the SE were modulated by the repetition/non
repetition of task features. Moreover, the JSE was differently modulated by the
gender composition of the two individuals involved in the shared task and by
their interpersonal relationship. Taken together, our results do not support a
pure social explanation of the JSE, nevertheless, they show the independent role
of different social factors in modulating the effect.
PMID- 26421449
TI - Change Detection in Visual Short-Term Memory: The Relative Impact of Pairwise
Switches and Identity Substitutions.
AB - Numerous kinds of visual event challenge our ability to keep track of the objects
that populate our visual environment from moment to moment. These include blinks,
occlusion, shifting visual attention, and changes to object's visual and spatial
properties over time. These visual events may lead to objects falling out of our
visual awareness, but can also lead to unnoticed changes, such as undetected
object replacements and positional exchanges. Current visual memory models do not
predict which visual changes are likely to be the most difficult to detect. We
examine the accuracy with which switches (where two objects exchange locations)
and substitutions (where one or two objects are replaced) are detected. Inferior
performance for one-object substitutions versus two-objects switches, along with
superior performance for two-object substitutions versus two-object switches was
found. Our results are interpreted in terms of object file theory, trade-offs
between diffused and localized attention, and net visual change.
PMID- 26421450
TI - Tactile Stimuli Increase Effects of Modality Compatibility in Task Switching.
AB - Modality compatibility refers to the similarity of stimulus modality and modality
of response-related sensory consequences. Previous dual-task studies found
increased switch costs for modality incompatible tasks (auditory-manual/visual
vocal) compared to modality compatible tasks (auditory-vocal/visual-manual). The
present task-switching study further examined modality compatibility and
investigated vibrotactile stimulation as a novel alternative to visual
stimulation. Interestingly, a stronger modality compatibility effect on switch
costs was revealed for the group with tactile-auditory stimulation compared to
the visual-auditory stimulation group. We suggest that the modality compatibility
effect is based on crosstalk of central processing codes due to ideomotor
"backward" linkages between the anticipated response effects and the stimuli
indicating this response. This crosstalk is increased in the tactile-auditory
stimulus group compared to the visual-auditory stimulus group due to a higher
degree of ideomotor-compatibility in the tactile-manual tasks. Since crosstalk
arises between tasks, performance is only affected in task switching and not in
single tasks.
PMID- 26421452
TI - Additional Post-Concussion Impact Exposure May Affect Recovery in Adolescent
Athletes.
AB - Repeat concussion has been associated with risk for prolonged and pronounced
clinical recovery in athletes. In this study of adolescent athletes, we examined
whether an additional head impact within 24 h of a sports-related concussion
(SRC) is associated with higher symptom burden and prolonged clinical recovery
compared with a single-injury group. Forty-two student-athletes (52% male, mean
age = 14.9 years) diagnosed with an SRC in a concussion clinic were selected for
this study: (1) 21 athletes who sustained an additional significant head impact
within 24 h of the initial injury (additional-impact group); (2) 21 single-injury
athletes, age and gender matched, who sustained only one discrete concussive blow
to the head (single-injury group). Groups did not differ on initial injury
characteristics or pre-injury risk factors. The effect of injury status (single-
vs. additional-impact) was examined on athlete- and parent-reported symptom
burden (at first clinic visit) and length of recovery (LOR). Higher symptom
burden was reported by the athletes and parents in the additional-impact group at
the time of first visit. The additional-impact group also had a significantly
longer LOR compared with the single-injury group. These findings provide
preliminary, hypothesis-generating evidence for the importance of immediate
removal from play following an SRC to protect athletes from re-injury, which may
worsen symptoms and prolong recovery. The retrospective study design from a
specialized clinical sample points to the need for future prospective studies of
the relationship between single- and additional-impact injuries on symptom burden
and LOR.
PMID- 26421454
TI - Protein extraction methods of tomato, environmental changes of the Amazon Forest
in Roraima (northernmost part of Brazil) for the last 1000 years, and
histological characteristics of a dolphin species.
PMID- 26421453
TI - Clinicopathologic features and outcomes of lymphoplasmacytic lymphoma patients
with monoclonal IgG or IgA paraprotein expression.
AB - Lymphoplasmacytic lymphoma secreting IgG or IgA (non-IgM LPL) is rarely seen.
Systematic studies of the clinical features and treatment outcomes are lacking in
these patients. This study evaluated 17 patients with non-IgM LPL. The
paraprotein secreted by these tumors was IgA (n=8; 47%) and IgG (n=9; 53%). The
median serum level of paraprotein was 2,475 mg/dl (range=747-5260) for IgA and
2580 mg/dl (range=1900-7100) for IgG. The IgA-LPL group was more likely to
present with B symptoms, a high beta2-microglobulin level and extramedullary
involvement. Compared with patients with Waldenstrom macroglobulinemia (WM),
patients with non-IgM LPL showed similar clinical and pathologic features, but a
higher mortality within the first year after diagnosis (p<0.001) and worse
overall survival (p=0.024), with no difference in progression-free survival and
disease-specific survival. Rituximab alone or rituximab-based therapy was used
frequently and was effective as either first-line or salvage therapy.
PMID- 26421455
TI - Infinitesimal Hartman-Grobman Theorem in Dimension Three.
AB - In this paper we give the main ideas to show that a real analytic vector field in
R3 with a singular point at the origin is locally topologically equivalent to its
principal part defined through Newton polyhedra under non-degeneracy conditions.
PMID- 26421456
TI - An Analysis of Total Phosphorus Dispersion in Lake Used As a Municipal Water
Supply.
AB - In Belem city is located the potable water supply system of its metropolitan
area, which includes, in addition to this city, four more municipalities. In this
water supply complex is the Agua Preta lake, which serves as a reservoir for the
water pumped from the Guama river. Due to the great importance of this lake for
this system, several works have been devoted to its study, from the monitoring of
the quality of its waters to its hydrodynamic modeling. This paper presents the
results obtained by computer simulation of the phosphorus dispersion within this
reservoir by the numerical solution of two-dimensional equation of advection
diffusion-reaction by the method theta/SUPG. Comparing these results with data
concentration of total phosphorus collected from November 2008 to October 2009
and from satellite photos show that the biggest polluters of the water of this
lake are the domestic sewage dumps from the population living in its vicinity.
The results obtained indicate the need for more information for more precise
quantitative analysis. However, they show that the phosphorus brought by the
Guama river water is consumed in an area adjacent to the canal that carries this
water into the lake. Phosphorus deposits in the lake bottom should be monitored
to verify their behavior, thus preventing the quality of water maintained
therein.
PMID- 26421457
TI - Linking environmental drivers with amphibian species diversity in ponds from
subtropical grasslands.
AB - Amphibian distribution patterns are known to be influenced by habitat diversity
at breeding sites. Thus, breeding sites variability and how such variability
influences anuran diversity is important. Here, we examine which characteristics
at breeding sites are most influential on anuran diversity in grasslands
associated with Araucaria forest, southern Brazil, especially in places at risk
due to anthropic activities. We evaluate the associations between habitat
heterogeneity and anuran species diversity in nine body of water from September
2008 to March 2010, in 12 field campaigns in which 16 species of anurans were
found. Of the seven habitat descriptors we examined, water depth, pond surface
area and distance to the nearest forest fragment explained 81% of total species
diversity. Water depth, margin vegetation type, surface area and distance to the
next body of water explained between 31-74% of the variance in abundance of nine
of the 16 species. Thus, maintenance of body of water, of the vegetation along
the water edge and natural forest fragments in the grasslands, along with fire
control (used to renovation of pasture), are fundamentally important for the
maintenance of anuran species diversity through the conservation of their
breeding sites.
PMID- 26421458
TI - Antioxidant status in women with uterine leiomyoma: relation with sex hormones.
AB - Uterine leiomyomas are benign soft-tissues tumors that arise from uterine smooth
muscle tissue. Etiopathogenesis of leiomyomas is not well understood. We aimed to
examine whether antioxidant enzyme activities and lipid hydroperoxides level in
patients with leiomyoma are influenced by changes in sex hormones and
gonadotropins (estradiol (E2), progesterone, FSH, and LH) during menstrual cycle
and in postmenopause. The material consisted of blood and uterine tissue
specimens. Hormone concentrations were determined and assays for superoxide
dismutase, catalase, glutathione peroxidase and glutathione reductase activities
and lipid hydroperoxides concentration were performed. In blood of examined
women, a significant difference in catalase, glutathione peroxidase and
glutathione reductase activity was recorded among the phases. There was also a
positive correlation between the estradiol/progesterone concentration and the
catalase activity. Progesterone negatively correlated with lipid hydroperoxides
level. In myoma tissue, we recorded a phase-related difference in lipid
hydroperoxides level and activities of superoxide dismutase, glutathione
peroxidase activities, and glutathione reductase. Negative correlation was
observed between FSH and glutathione peroxidase. The results suggest that
antioxidant status in patients with uterine leiomyoma is influenced by the
changes in sex hormones during the menstrual cycle and in postmenopause,
indicating a role of the observed relationship in the leiomyoma etiology.
PMID- 26421459
TI - Growing a New Study: Environmental Influences on Child Health Outcomes.
PMID- 26421460
TI - Q Fever Outbreak Among Travelers to Germany Who Received Live Cell Therapy-
United States and Canada, 2014.
AB - During September-November 2014, the New York State Department of Health (NYSDOH)
was notified of five New York state residents who had tested seropositive for
Coxiella burnetii, the causative agent of Q fever. All five patients had symptoms
compatible with Q fever (e.g., fever, fatigue, chills, and headache) and a
history of travel to Germany to receive a medical treatment called "live cell
therapy" (sometimes called "fresh cell therapy") in May 2014. Live cell therapy
is the practice of injecting processed cells from organs or fetuses of nonhuman
animals (e.g., sheep) into human recipients. It is advertised to treat a variety
of health conditions. This practice is unavailable in the United States; however,
persons can travel to foreign locations to receive injections. Local health
departments interviewed the patients, and NYSDOH notified CDC and posted a report
on CDC's Epidemic Information Exchange to solicit additional cases. Clinical and
exposure information for each patient was reported to the Robert Koch Institute
in Germany, which forwarded the information to local health authorities. A Canada
resident who also received live cell therapy in May 2014 was diagnosed with Q
fever in July 2014. Clinicians should be aware of health risks, such as Q fever
and other zoonotic diseases, among patients with a history of receiving treatment
with live cell therapy products.
PMID- 26421461
TI - Effectiveness, Good Tolerability, and High Compliance of Doses of Risperidone
Long-Acting Injectable Higher Than 75 mg in People With Severe Schizophrenia: A 3
Year Follow-Up.
AB - Tolerability and effectiveness of antipsychotics are important to increase
treatment compliance in people with schizophrenia. The aim of this study was to
evaluate effectiveness, tolerability, and adherence to treatment with high doses
of risperidone long-acting injectable (RLAI) in patients with severe
schizophrenia.It is a 3-year prospective, observational study of patients with
severe (Clinical Global Impression Severity scale [CGI-S] score of >=5)
schizophrenia according to International Classification of Diseases (ICD-10)
criteria. Subjects were the consecutive 60 who first underwent treatment with
RLAI with doses of 75 mg or higher every 14 days to get clinical
stabilization.Assessment included the following: CGI-S, World Health Organization
Disability Assessment Schedule, Camberwell Assessment of Need (CAN), Medication
Adherence Rating Scale, laboratory tests, weight, and hospital admissions.The
mean (SD) dose of RLAI was 111.2 (9.1) mg per 14 days. Tolerability was good and
there were almost no interruptions due to adverse effects or to relevant
biological parameters alterations. Also, weight gain was not
significant.Retention rate in treatment after 3 years was 95%. Clinical Global
Impression Severity (P < 0.01) and Camberwell Assessment of Need (P < 0.01)
decreased and also Disability Assessment Schedule in the 4 areas (P < 0.01).
Medication Adherence Rating Scale score increased from 3.6 (0.7) to 8.9 (0.9) (P
< 0.001). There were significantly few hospital admissions than during the
previous 36 months (1.9 [1.3] vs 0.31 [0.2], P < 0.001).As a conclusion, we
highlight that the effectiveness and tolerability of 75 mg or higher every 14
days of RLAI were high, being useful in improving treatment adherence in patients
with severe schizophrenia, getting good clinical and functional outcomes.
PMID- 26421462
TI - Treatment of relapsed urothelial bladder cancer with vinflunine: real-world
evidence by the Hellenic Genitourinary Cancer Group.
AB - Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a
third-generation antimicrotubuline inhibitor and is currently the only approved
drug for second-line treatment across the European Union. We conducted a
retrospective analysis assessing the efficacy and safety of vinflunine in 71
Greek patients with relapsed urothelial cancer who were treated between 2005 and
2014. An overall 84% of our patients received vinflunine as second-line
treatment, 77% had a performance status of Eastern Cooperative Oncology Group
scale 0 or 1, and 30% had liver metastasis at the time of vinflunine
administration. A median of four cycles of vinflunine were administered (range 1
16). The most common reported adverse events were constipation, fatigue, and
anemia. Median progression-free survival was 6.2 months (95% confidence interval:
4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21).
Two patients (3%) achieved a complete remission, seven a partial remission (10%),
and 22 (31%) had stable disease according to an intention-to-treat analysis.
Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group
performance status greater than 1 were independent adverse prognostic factors.
Stratification according to the Bellmunt risk model was also associated with
progression-free survival and overall survival in our population. Vinflunine
appears to be a safe and effective treatment modality for relapsed urothelial
cancer. More effective therapies and more accurate prognostic algorithms should
be sought.
PMID- 26421463
TI - Glycodendrimersomes from Sequence-Defined Janus Glycodendrimers Reveal High
Activity and Sensor Capacity for the Agglutination by Natural Variants of Human
Lectins.
AB - A library of eight amphiphilic Janus glycodendrimers (Janus-GDs) presenting D
lactose (Lac) and a combination of Lac with up to eight methoxytriethoxy (3EO)
units in a sequence-defined arrangement was synthesized via an iterative modular
methodology. The length of the linker between Lac and the hydrophobic part of the
Janus-GDs was also varied. Self-assembly by injection from THF solution into
phosphate-buffered saline led to unilamellar, monodisperse glycodendrimersomes
(GDSs) with dimensions predicted by Janus-GD concentration. These GDSs provided a
toolbox to measure bioactivity profiles in agglutination assays with sugar
binding proteins (lectins). Three naturally occurring forms of the human
adhesion/growth-regulatory lectin galectin-8, Gal-8S and Gal-8L, which differ by
the length of linker connecting their two active domains, and a single amino acid
mutant (F19Y), were used as probes to study activity and sensor capacity.
Unpredictably, the sequence of Lac on the Janus-GDs was demonstrated to determine
bioactivity, with the highest level revealed for a Janus-GD with six 3EO groups
and one Lac. A further increase in Lac density was invariably accompanied by a
substantial decrease in agglutination, whereas a decrease in Lac density resulted
in similar or lower bioactivity and sensor capacity. Both changes in topology of
Lac presentation of the GDSs and seemingly subtle alterations in protein
structure resulted in different levels of bioactivity, demonstrating the presence
of regulation on both GDS surface and lectin. These results illustrate the
applicability of Janus-GDs to dissect structure-activity relationships between
programmable cell surface models and human lectins in a highly sensitive and
physiologically relevant manner.
PMID- 26421464
TI - Isolated sphenoid sinus disease: An overlooked cause of headache.
AB - OBJECTIVES: The aim of this study was to evaluate patients who underwent
endoscopic sphenoid sinus surgery for isolated sphenoid sinus disease. We also
investigated the impact of sphenoid sinus surgery on headache intensity. MATERIAL
AND METHODS: Twenty-one consecutive patients who underwent endoscopic
sphenoidotomy for isolated sphenoid sinus disease were included in the study.
Diagnosis of isolated sphenoid sinus pathology was based on history, physical
examination, and radiologic evaluation. All patients had headache with various
localizations. Pre- and postoperative headache intensity of patients was scored
using a visual analogue scale (VAS). RESULTS: The most common location of
headache was the vertex (24%). The preoperative and postoperative mean VAS scores
for headache were 8.24 +/- 0.94 and 2.67 +/- 1.49, respectively. Statistical
comparison revealed a significant improvement in headache intensity (p < 0.01).
Polyps (33.3%) were the most common pathology, followed by inflammation (23.8%).
CONCLUSIONS: The most common presenting symptom of isolated sphenoid sinus
disease is headache. In this study, we demonstrated that headache induced by
isolated sphenoid disease can be relieved by endoscopic sphenoidotomy. Sphenoid
sinus disease should be considered in the differential diagnosis of patients
presenting with subacute or chronic headache.
PMID- 26421465
TI - Ibandronate treatment of diffuse sclerosing osteomyelitis of the mandible: Pain
relief and insight into pathogenesis.
AB - PURPOSE: Diffuse sclerosing osteomyelitis of the mandible (DSO) is a rare and
poorly understood disease. Current treatment protocols, including steroid or
analgesic medication and corticotomies, show poor or frustrating outcome results
and are accompanied by potentially severe side effects. The aim of this study was
to determine whether there is a beneficial role of infusions with nitrogen
containing bisphosphonates (ibandronate) in acute conditions of DSO. MATERIAL AND
METHODS: Eleven patients were enrolled in the study. In acute conditions of
treatment-resistant DSO, single-shot infusions of ibandronate (6 mg) were
administered. Pain levels were documented 10 days before and after the infusion
on a visual analogue scale (VAS). Patients were monitored regularly. RESULTS: Of
the 11 patients, 10 showed a distinct improvement in pain (based on VAS scores)
within 48-72 h after infusion. The pain levels of the patients were significantly
lower after ibandronate infusions (p < 0.01). The majority of patients were free
or almost free of complaints over the following months. Four of the 11 patients
returned for repeated infusions. At the time of writing, no severe side effects
have been observed, and in particular there has been no case of medication
related jaw osteonecrosis. CONCLUSION: We conclude that single-shot
bisphosphonate infusions on demand are promising treatment alternatives in acute
DSO. Single-shot bisphosphonate infusions of ibandronate were well tolerated and
resulted in distinct, long lasting improvement in subjective pain levels based on
VAS scores.
PMID- 26421466
TI - The association of cleft severity and cleft palate repair technique on hearing
outcomes in children in northern Finland.
AB - BACKGROUND: The consequences of cleft lip and palate include scaring, dental
malformations, tooth misalignment, speech problems, and hearing loss. Otitis
media with effusion causing hearing loss is a problem for many cleft palate
patients. METHODS: This study examines the association among cleft severity,
palate repair technique, and hearing outcomes in children from northern Finland
with clefts, aged 3-9 years. The study included 90 cleft patients who were
treated at the Oulu University Hospital Cleft Lip and Palate Center between 1998
and 2011. The severity of the cleft, the surgical technique used to repair the
palate, audiogram configuration data, and the need for ventilation tube placement
were determined retrospectively from patient records. RESULTS: Only 3.3% of cleft
patients had an abnormal pure tone average hearing threshold representing
abnormal hearing. Neither the surgical technique used to repair the cleft palate
nor the severity of the cleft was a significant factor related to hearing loss or
to the number of ventilation tubes required. Hearing improved significantly with
increasing age over a span of 6 years. CONCLUSIONS: Continuous follow-up with
proactive placement of ventilation tubes before or at the time of palatoplasty
results in hearing outcomes in cleft children that are similar to those reported
in non-cleft children.
PMID- 26421467
TI - Surgical learning curve in performing palatoplasty: A retrospective study in 200
patients.
AB - OBJECTIVES: The aim of the study was to assess the influence of the experience of
the surgeon on the occurrence of fistulas following palatoplasty. MATERIALS AND
METHODS: A retrospective review was performed of consecutive children treated
between 2006 and 2013 for cleft palate by a single surgeon. Cleft palate repair
was performed using the von Langenbeck technique, Furlow palatoplasty, buccal
flap or Vomer flap. Data was collected for age, sex, date of birth, syndrome,
adoption, cleft palate type, type of repair, cleft width, fistula occurrence and
location of fistula. RESULTS: A total of 276 operations were performed in 200
children (Veau I, II, III, IV). Mean age at surgery was 21.9 months (range: 6.2
months to 26 years 8.3 months). Postoperatively, palatal fistulas occurred in
eight patients (4.0%), however, the incidence was 3.0% in the non-adoption group
and 9.7% in the adoption population. In this study there was no statistically
significant evidence of a surgical learning curve, and no significant
associations between fistula rate and sex, adoption, syndrome, cleft type, cleft
width, or type of repair. CONCLUSION AND CLINICAL RELEVANCE: This study
demonstrates a fistula formation rate of 3.0% for the non-adoption population and
9.7% for the adoption population. There was no statistically significant evidence
of a learning curve during the first few years of performing cleft palate repair.
No other independent risk factors for postoperative fistula formation were
identified; however, the benefit of a vomer flap and subsequent reduction in
fistula incidence was demonstrated.
PMID- 26421468
TI - Three-dimensional quantitative evaluation of midfacial skeletal changes after
trans-sutural distraction osteogenesis for midfacial hypoplasia in growing
patients with cleft lip and palate.
AB - PURPOSE: Trans-sutural distraction osteogenesis (TSDO) is an alternative method
for the early treatment of midfacial hypoplasia in growing patients with cleft
lip and palate (CLP). The purpose of this study was to analyze three-dimensional
(3D) midfacial skeletal changes after TSDO and to explore the mechanism in this
process. MATERIAL AND METHODS: All patients with nonsyndromic CLP who underwent
bone-borne TSDO for midfacial hypoplasia from 2005 to 2014 were reviewed in this
retrospective study. 3D morphological and quantitative measurement analyses were
performed to evaluate midfacial skeletal changes by superimposition of
preoperative and postoperative computed tomographic images. RESULTS: Twenty-six
patients with mean age of 11.5 years met the inclusion criteria. The 3D
morphological findings exhibited the most significant suture stress changes at
the pterygomaxillary suture area, with obvious bone generation in all patients.
The whole midfacial skeleton had progressively increased advancement in a
craniocaudal direction along the midface segment, associated with morphological
changes in skeleton itself. The 3D quantitative measurement findings showed
differential advancement of each landmark at the maxillary alveolar, zygomatic
bone, orbital rim, and nasal bone, which was consistent with morphological
findings. CONCLUSIONS: TSDO allows rotation advancement of the midfacial skeleton
to achieve occlusal correction and facial harmony through the mechanism of both
suture remodeling and bone remodeling.
PMID- 26421469
TI - Quality of life after different oncologic interventions in head and neck cancer
patients.
AB - Patient reported outcomes following head and neck cancer are of great importance,
given the functional, psychological, and social impacts of the disease and its
treatment. In addition, not only is the number of publications on health-related
quality of life (HRQOL) increasing in a variety of specialties, but there is also
a growing awareness of the potential role of HRQOL in practice. Therefore, we
aimed to investigate the HRQOL of head and neck cancer patients following
different oncologic interventions, using an internationally established test. In
this cross-sectional study, we included three different groups of 32 patients
each. Participants had histologically confirmed invasive oral squamous cell
carcinoma (OSCC) in the anterior floor of the mouth. Group allocation was based
on treatment modality, as follows: only surgery (group 1), operation and adjuvant
radiotherapy (XRT) (group 2), and the additional presence of osteoradionecrosis
(ORN) (group 3). All patients were questioned about their HRQOL, using the
standardized University of Washington Quality of Life Questionnaire (UW-QOL).
Surveys for groups 1 and 2 were conducted at least 24 months after the end of
tumor-related treatment, in cases of ORN (group 3) 12 months after completion of
disease-related treatment. A total of 96 patients were included into this study.
The mean age was 62.79 +/- 8.93 years. The patients in groups 1 and 2 revealed a
reduced quality of life, of a greater magnitude after radiation therapy. Patients
felt that radiotherapy was much worse than surgery; however, half of the patients
stated that they would repeat radiation therapy if necessary. The subjective
evaluation of the HRQOL after surgery and radiotherapy was a valuable instrument
for assessing the rehabilitation of patients in the context of their function and
quality of life. Radiation therapy can be considered a trigger of functional
limitations and emotional distress that contributes to decreased HRQOL in
patients with head and neck cancer.
PMID- 26421470
TI - The 3dMD photogrammetric photo system in cranio-maxillofacial surgery: Validation
of interexaminer variations and perceptions.
AB - BACKGROUND: Three-dimensional photography of the face is increasingly used to
overcome the downsides of conventional photography or anthropometry regarding
reliable evaluation. However, the precision of such a system has to be validated
before it can be implemented for clinical use. MATERIAL AND METHODS: Eight people
were photographed with the 3dMDface system using lighting from sets of 2 * 4
compact fluorescent lights in a clinical photography room without natural light
sources. Two different operators then individually, and without interaction,
marked 27 different anatomical landmarks using the 3dMD Patient software. During
this process, the operators were fully blinded against each other. The purpose of
the study was to determine the repeatability and accuracy of the system when used
by different operators and at different times. The 3D differentiation was
analyzed using mixed ANOVA with person as the random factor, and operator,
repetition, and landmark as the fixed factors. The ANOVA was followed by a Ryan
Einot-Gabriel-Welsch F post-hoc test for landmarks. RESULTS: Statistical analysis
grouped the landmarks into three subgroups: high precision, medium precision and
low precision. CONCLUSIONS: Virtual 3D models derived from the 3dMDface system
not only provide a high level of technical precision but also of intra- and
interobserver reliability regarding landmark identification. However, some of the
classical landmarks are not reliable when it comes to virtual models; these are
generally landmarks that examiners of real patients would tend to identify using
palpation of underlying bony structures, such as the soft gonion.
PMID- 26421471
TI - The relationship between changes in the expression of growth associated protein
43 and functional recovery of the injured inferior alveolar nerve following
transection without repair in adult rats.
AB - OBJECTIVE: The objective of this study was to analyze the changes in the
expression of growth associated protein-43 (GAP-43) in trigeminal ganglions (TGs)
and in the distal stumps of transected inferior alveolar nerves (IANs), and to
clarify the relationship between these changes and functional recovery of the
transected IAN without repair using a rat IAN axotomy model. MATERIAL AND
METHODS: Following transection, GAP-43 expression was measured at multiple time
points. The functional recovery of the transected IAN was evaluated based on the
compound muscle action potentials recorded from the digastric muscle. RESULTS:
GAP-43 expression in TGs was significantly higher at 2, 7, 14, 28, and 56 days
following IAN transection compared to that in samples from sham-operated rats (p
< 0.0005, p < 0.0005, p < 0.0005, p = 0.007, and p = 0.023, respectively). GAP-43
expression in the distal stumps of transected IANs was significantly higher at 2,
7, 14, and 28 days following IAN transection compared to that in samples taken
from sham rats (p < 0.0005, p < 0.0005, p < 0.0005, and p = 0.009, respectively).
GAP-43 expression in the distal stumps of transected IANs returned nearly to sham
levels by day 56 following IAN transection. On days 7, 14, 28, and 56 following
transection, the amplitude of the compound muscle action potential gradually
increased, the latency gradually decreased, and the duration gradually increased.
The amplitude, latency, and duration of the compound muscle action potentials
nearly returned to sham levels on post-transection day 56. CONCLUSIONS: Time
dependent changes in the expression of GAP-43 in both TGs and distal stumps of
transected IANs without repair are synchronously consistent with the regeneration
and functional recovery of the transected IAN. The recovery of the amplitude,
latency, and duration of the compound muscle action potentials indicates
increased myelination and increased axon density of the regenerated nerve fibers.
PMID- 26421472
TI - Approach to intraoperative electromagnetic navigation in orthognathic surgery: A
phantom skull based trial.
AB - INTRODUCTION: Intraoperative guidance using electromagnetic navigation is an
upcoming method in maxillofacial surgery. However, due to their unwieldy
structures, especially the line-of-sight problem, optical navigation devices are
not used for daily orthognathic surgery. Therefore, orthognathic surgery was
simulated on study phantom skulls, evaluating the accuracy and handling of a new
electromagnetic tracking system. MATERIAL AND METHODS: Le-Fort I osteotomies were
performed on 10 plastic skulls. Orthognathic surgical planning was done in the
conventional way using plaster models. Accuracy of the gold standard, splint
based model surgery versus an electromagnetic tracking system was evaluated by
measuring the actual maxillary deviation using bimaxillary splints and
preoperative and postoperative cone beam computer tomography imaging. The
distance of five anatomical marker points were compared pre- and postoperatively.
RESULTS: The electromagnetic tracking system was significantly more accurate in
all measured parameters compared with the gold standard using bimaxillary splints
(p < 0.01). The data shows a discrepancy between the model surgical plans and the
actual correction of the upper jaw of 0.8 mm. Using the electromagnetic tracking,
we could reduce the discrepancy of the maxillary transposition between the
planned and actual orthognathic surgery to 0.3 mm on average. DISCUSSION: The
data of this preliminary study shows a high level of accuracy in surgical
orthognathic performance using electromagnetic navigation, and may offer greater
precision than the conventional plaster model surgery with bimaxillary splints.
CONCLUSION: This preliminary work shows great potential for the establishment of
an intraoperative electromagnetic navigation system for maxillofacial surgery.
PMID- 26421473
TI - Predictive Significance of Tumor Grade Using 256-Slice CT Whole-Tumor Perfusion
Imaging in Colorectal Adenocarcinoma.
AB - RATIONALE AND OBJECTIVES: The preoperative assessment of tumor grade has
important clinical implications for the treatment and prognosis of patients with
colorectal adenocarcinomas. The purpose of this study is to investigate the
predictive significance of colorectal adenocarcinoma grade using 256-slice whole
tumor computed tomography (CT) perfusion. MATERIALS AND METHODS: Fifty-three
patients with proven colorectal adenocarcinomas were enrolled. All of them
underwent 256-slice whole-tumor CT perfusion. They were divided into two
different subgroups according to postoperative pathological results: low grade
and high grade. The Kruskal-Wallis test or one-way analysis of variance was used
for comparison of CT perfusion parameters between different tumor grades.
Multivariant correlation between pathologic tumor stage, histologic tumor
differentiation, and whole-tumor CT perfusion parameters was evaluated by
Spearman rank correlation coefficient. According to receiver operating
characteristic (ROC) curves, perfusion parameters including blood flow (BF), peak
enhancement index (PEI), blood volume (BV), and time to peak (TTP) of 53 patients
were analyzed, and the sensitivity, specificity, and accuracy of these parameters
in predicting tumor grade were calculated. RESULTS: There were significant
differences in BF and TTP between low-grade and high-grade tumors. According to
the ROC curve, BF and TTP were of diagnostic significance, with the area under
the curve values of 0.828 and 0.736, respectively. The diagnostic threshold of BF
was 32.12 mL/min/100 g and that of TTP was 18.10 seconds. CONCLUSIONS: The CT
perfusion parameters (BF, TTP) of first-pass 256-slice whole-tumor CT perfusion
imaging can reflect tumor grade in colorectal adenocarcinoma.
PMID- 26421475
TI - The basis, ethics and provision of palliative care for dementia: A review.
AB - Interest in palliative care for people with dementia has been around for over two
decades. There are clinical and ethical challenges and practical problems around
the implementation of good quality palliative care in dementia. This narrative
review of the literature focuses on the rationale or basis for services, some of
the ethical issues that arise (particularly to do with artificial nutrition and
hydration) and on the provision and implementation of services. We focus on the
most recent literature. The rationale for palliative care for people with
dementia is based on research and on an identified need for better clinical care.
But the research largely demonstrates a paucity of good quality evidence, albeit
particular interventions (and non-interventions) can be justified in certain
circumstances. Numerous specific clinical challenges in end-of-life care for
people with dementia are ethical in nature. We focus on literature around
artificial nutrition and hydration and conclude that good communication,
attention to the evidence and keeping the well-being of the person with dementia
firmly in mind will guide ethical decision-making. Numerous challenges surround
the provision of palliative care for people with dementia. Palliative care in
dementia has been given definition, but can still be contested. Different
professionals provide services in different locations. More research and
education are required. No single service can provide palliative care for people
with dementia.
PMID- 26421474
TI - Vaginal atrophy of women in postmenopause. Results from a multicentric
observational study: The AGATA study.
AB - OBJECTIVES: Prevalence of vulvar-vaginal atrophy (VVA) has been always
investigated by phone or web interview without any objective evaluation.
Objective signs associated with symptoms of VVA are now termed genitourinary
syndrome of menopause (GSM). This multi-centric study was performed in order to
provide nation-wide data on the prevalence and management of GSM. METHODS: Nine
hundred thirteen females, 59.3 +/- 7.4 years old asking for a routine
gynecological examination were recruited. Diagnosis of GSM was based on patient
sensation of vaginal dryness, any objective sign of VVA and a pH > 5. RESULTS: A
722/913 (79.1%) women were diagnosed with GSM with a prevalence ranging from
64.7% to 84.2%, starting from 1 to 6 years after menopause. Sedentary women were
at higher risk of GSM (OR 1.8, 95% CI: 1.3-2.5; p = 0.0005). Recent vaginal
infection was more likely in women with GSM (OR 2.48, 95% CI: 1.33-4.62; p =
0.0041). Symptoms reported by women with GSM were vaginal dryness (100%),
dyspareunia (77.6%), burning (56.9%), itching (56.6%) and dysuria (36.1%). Signs
detected by gynecologists were mucosal dryness (99%), thinning of vaginal rugae
(92.1%), pallor of the mucosa (90.7%), mucosal fragility (71.9%) and petechiae
(46.7%). Only 274 (30%) of women had had a previous diagnosis of VVA/GSM. These
were treated either with no therapy (9.8%), systemic hormone (9.2%), local
hormone (44.5%) or local non-hormonal (36.5%) therapy. At the time of our
investigation 266 of them (97.1%) still had the disorder. CONCLUSIONS: GSM is a
common, under-diagnosed and under-treated disorder. Measures to improve its early
detection and its appropriate management are needed.
PMID- 26421476
TI - Does repeated palpation-digitization of pelvic landmarks for measurement of
innominate motion introduce a systematic error?--A psychometric investigation.
AB - BACKGROUND: Palpation-digitization technique for measurement of innominate motion
involves repeated manual palpation-digitization of pelvic landmarks, which could
introduce a systematic variation between subsequent trials and thereby influence
final innominate angular measurement. OBJECTIVES: The aim of this study is to
quantify the effect of repeated palpation-digitization errors on overall
variability of innominate vector length measurements; and to determine if there
is a systematic variation between subsequent repeated trials. METHOD: A single
group repeated measures study, using four testers and fourteen healthy
participants, was conducted. Four pelvic landmarks, left and right posterior
superior iliac spine and anterior superior iliac spine, were palpated and
digitized using 3D digitizing stylus of Polhemus electromagnetic tracking device,
for ten consecutive trials by each tester in their random order. The ten
individual trials of innominate vector lengths measured by each tester for each
participant were used for the analysis. RESULTS AND CONCLUSIONS: Repeated
measures ANOVA demonstrated a very small effect of repeated trial factor
(<=0.66%) as well as error component (<=0.32%) on innominate vector length
variability. Further, residual versus order plots demonstrated a random pattern
of errors across zero; thus indicating no systematic variation between subsequent
trials of innominate vector length measurements.
PMID- 26421477
TI - Complications after intraoral vertical ramus osteotomy: relationship to the shape
of the osteotomy line.
AB - Intraoral vertical ramus osteotomy (IVRO) is used widely to correct mandibular
prognathism. However, several disadvantages of this procedure have been reported,
such as condylar luxation and bony interference at the osteotomy site. The aim of
this study was to survey the incidence of complications (condylar luxation and
bony interference) based on the shape of the osteotomy line. One hundred and
eighty-five rami in 118 patients with jaw deformities, which were treated with
IVRO, were examined retrospectively. The shape of the osteotomy line and the
postoperative complications were examined on panoramic radiographs. Osteotomy
lines were classified into three types: vertical, C-shaped, and oblique. Of the
185 osteotomy sites, 98 were vertical, 37 C-shaped, and 50 oblique. Condylar
luxation was found in six rami (3.2%); four had undergone vertical osteotomy and
two had undergone C-shaped osteotomy. Bony interference occurred in seven rami
(3.8%), all with vertical type osteotomy lines. Most complications occurred in
the vertical type cases and no complications were found in oblique type cases.
Condylar luxation was found mainly in unilateral IVRO cases and bony interference
was found in bilateral IVRO cases. These results suggest that the oblique type of
osteotomy line has the advantage of avoiding complications.
PMID- 26421478
TI - The use of free flaps in skull base reconstruction.
AB - Skull base tumours are rare, comprising less than 1% of all tumours of the head
and neck. Surgical treatment of these tumours involves the approach, the
resection, and the reconstruction of the defect, which present a challenge due to
the technical difficulty and anatomical complexity. A retrospective study of 17
patients with tumours involving the skull base, treated by resection and
immediate reconstruction using microsurgical free flaps, is presented; 11 were
men and six were women. The following types of flap were used: osteocutaneous
fibula flaps, fasciocutaneous anterolateral thigh flaps, and myocutaneous
latissimus dorsi flaps. The most common histology of the tumours was squamous
cell carcinoma. The most frequent point of origin was the paranasal sinuses
(58.8%). All of the free flaps used for reconstruction were viable. A
cerebrospinal fluid fistula occurred in two patients, and in one of these cases,
meningoencephalitis led to death. In conclusion, the reconstruction of large
defects of the skull base after ablation requires a viable tissue that in many
cases can be obtained only through the use of microvascular free flaps. The type
of flap to be selected depends on the anatomical structures and size of the
defect to be restored.
PMID- 26421479
TI - Correction to Molecular Umbrella-Amphotericin B Conjugates.
PMID- 26421480
TI - Municipal solid waste characterization and quantification as a measure towards
effective waste management in Ghana.
AB - Reliable national data on waste generation and composition that will inform
effective planning on waste management in Ghana is absent. To help obtain this
data on a regional basis, selected households in each region were recruited to
obtain data on rate of waste generation, physical composition of waste, sorting
and separation efficiency and per capita of waste. Results show that rate of
waste generation in Ghana was 0.47 kg/person/day, which translates into about
12,710 tons of waste per day per the current population of 27,043,093.
Nationally, biodegradable waste (organics and papers) was 0.318 kg/person/day and
non-biodegradable or recyclables (metals, glass, textiles, leather and rubbers)
was 0.096 kg/person/day. Inert and miscellaneous waste was 0.055 kg/person/day.
The average household waste generation rate among the metropolitan cities, except
Tamale, was high, 0.72 kg/person/day. Metropolises generated higher waste
(average 0.63 kg/person/day) than the municipalities (0.40 kg/person/day) and the
least in the districts (0.28 kg/person/day) which are less developed. The waste
generation rate also varied across geographical locations, the coastal and forest
zones generated higher waste than the northern savanna zone. Waste composition
was 61% organics, 14% plastics, 6% inert, 5% miscellaneous, 5% paper, 3% metals,
3% glass, 1% leather and rubber, and 1% textiles. However, organics and plastics,
the two major fractions of the household waste varied considerably across the
geographical areas. In the coastal zone, the organic waste fraction was highest
but decreased through the forest zone towards the northern savanna. However,
through the same zones towards the north, plastic waste rather increased in
percentage fraction. Households did separate their waste effectively averaging
80%. However, in terms of separating into the bin marked biodegradables, 84%
effectiveness was obtained whiles 76% effectiveness for sorting into the bin
labeled other waste was achieved.
PMID- 26421481
TI - Anaerobic digestion of pre-fermented potato peel wastes for methane production.
AB - This study investigated the feasibility of anaerobic digestion (AD) of potato
peel waste (PPW) and its lactic acid fermentation residue (PPW-FR) for methane
(CH4) production. The experimental results showed that about 60-70% CH4 content
was obtained. The digester using PPW-FR as feedstock exhibited better performance
and produced a highest cumulative CH4 production of 273 L/kg VS fed, followed by
239 L/kg VS fed using PPW under the same conditions. However, with increasing
solid loadings of PPW-FR feedstock from 6.4% to 9.1%, the CH4 production was
inhibited. The generation, accumulation, and degradation of volatile fatty acids
(VFAs) in digesters were also investigated in this research.
PMID- 26421482
TI - Estimating travel and service times for automated route planning and service
certification in municipal waste management.
AB - Nowadays, route planning algorithms are commonly used to generate detailed work
schedules for solid waste collection vehicles. However, the reliability of such
schedules relies heavily on the accuracy of a number of parameters, such as the
actual service time at each collection location and the traversal times of the
streets (which depend on the specific day of the week and the time of day). In
this paper, we propose an automated classification and estimation algorithm that,
based on Global Positioning System data collected by the fleet, estimates such
parameters in a timely and accurate fashion. In particular, our approach is able
to classify automatically events like stops due to traffic jams, stops at traffic
lights and stops at collection sites. The system can also be used for automated
fleet supervision and in order to notify on a web site whether certain services
have been actually provided on a certain day, thus making waste management more
accountable to citizens. An experimentation carried out in an Italian
municipality shows the advantages of our approach.
PMID- 26421483
TI - MR imaging of cavernous sinus lesions: Pictorial review.
AB - The main purpose of this pictorial review is to highlight the important MR
imaging findings of various conditions involving the cavernous sinus in addition
to brief description of normal anatomy. The pathological conditions that can
involve the cavernous sinus can be categorized into infective, inflammatory,
granulomatous, vascular and neoplastic causes. Imaging, especially with MRI,
plays an important role not only in detection but also in definition of disease
extent and in characterization of the pathology. Currently, high-resolution MR
images clearly show various components of cavernous sinus which help in making a
proper diagnosis and thus appropriate further management.
PMID- 26421484
TI - Controlled release of cytokines using silk-biomaterials for macrophage
polarization.
AB - Polarization of macrophages into an inflammatory (M1) or anti-inflammatory (M2)
phenotype is important for clearing pathogens and wound repair, however chronic
activation of either type of macrophage has been implicated in several diseases.
Methods to locally control the polarization of macrophages is of great interest
for biomedical implants and tissue engineering. To that end, silk protein was
used to form biopolymer films that release either IFN-gamma or IL-4 to control
the polarization of macrophages. Modulation of the solubility of the silk films
through regulation of beta-sheet (crystalline) content enabled a short-term
release (4-8 h) of either cytokine, with smaller amounts released out to 24 h.
Altering the solubility of the films was accomplished by varying the time that
the films were exposed to water vapor. The released IFN-gamma or IL-4 induced
polarization of THP-1 derived macrophages into the M1 or M2 phenotypes,
respectively. The silk biomaterials were able to release enough IFN-gamma or IL-4
to repolarize the macrophage from M1 to M2 and vice versa, demonstrating the well
established plasticity of macrophages. High beta-sheet content films that are not
soluble and do not release the trapped cytokines were also able to polarize
macrophages that adhered to the surface through degradation of the silk protein.
Chemically conjugating IFN-gamma to silk films through disulfide bonds allowed
for longer-term release to 10 days. The release of covalently attached IFN-gamma
from the films was also able to polarize M1 macrophages in vitro. Thus, the
strategy described here offers new approaches to utilizing biomaterials for
directing the polarization of macrophages.
PMID- 26421485
TI - Secular Trends of Overweight and Obesity in Young Southern Californians 2008
2013.
AB - OBJECTIVE: To investigate secular trends in pediatric obesity in Southern
California between 2008 and 2013. STUDY DESIGN: In a population-based cohort
study, measured weight and height were extracted from electronic health records
of 1,331,931 patients aged 2-19 years who were enrolled in an integrated prepaid
health plan between 2008 and 2013. Outcomes were the prevalence of overweight and
obesity (body mass index-for-age >=85th percentile). RESULTS: The prevalence of
obesity was 19.1% in 2008 and decreased by 1.6% (95% CI, 1.7%-1.5%) by 2013,
corresponding to a relative decline of 8.4%. A significant decline was observed
across all ages, sexes, races, and socioeconomic groups, but the magnitude of the
decrease varied. The relative decline in obesity was stronger in boys (-9.3%)
than in girls (-7.2%), in children aged 2-5 years (-15.4%) and 6-11 years (
11.8%) than in adolescents aged 12-19 years (-4.5%), and in whites (-12.6%) and
Asians (-12.2%) than in Hispanics (-6.9%) and African Americans (-7.5%).
CONCLUSION: Secular trends from this large population-based cohort suggest that
overweight and obesity in boys and girls are declining across age and
racial/ethnic groups. However, the declines are less pronounced in adolescents
compared with children, in girls, and in some minority groups. Programs
addressing childhood obesity may need to be targeted.
PMID- 26421487
TI - Histologic Evidence of Intrapulmonary Bronchopulmonary Anastomotic Pathways in
Neonates with Meconium Aspiration Syndrome.
AB - We examined lung histology from 8 infants who died with meconium aspiration
syndrome in order to determine the presence of intrapulmonary bronchopulmonary
anastomotic pathways. Each infant required mechanical ventilation to treat
hypoxemic respiratory distress. Lung histology from each infant shows evidence of
prominent bronchopulmonary vascular connections.
PMID- 26421486
TI - Pollution, Poverty, and Potentially Preventable Childhood Morbidity in Central
California.
AB - OBJECTIVE: To measure ecological relationships between neighborhood pollution
burden, poverty, race/ethnicity, and pediatric preventable disease
hospitalization rates. STUDY DESIGN: Preventable disease hospitalization rates
were obtained from the 2012 California Office of Statewide Health Planning and
Development database, for 8 Central Valley counties. US Census Data was used to
incorporate zip code level factors including racial diversity and poverty rates.
The pollution burden score was calculated by the California Office of
Environmental Health Hazard Assessment using 11 indicators. Poisson-based
negative binomial regression was used for final analysis. Stratification of
sample by age, race/ethnicity, and insurance coverage was also incorporated.
RESULTS: Children experiencing potentially preventable hospitalizations are
disproportionately low income and under the age of 4 years. With every unit
increase in pollution burden, preventable disease hospitalizations rates increase
between 21% and 32%, depending on racial and age subgroups. Although living in a
poor neighborhood was not associated with potentially avoidable hospitalizations,
children enrolled in Medi-Cal who live in neighborhoods with lower pollution
burden and lower levels of poverty, face 32% lower risk for ambulatory care
sensitive condition hospitalization. Children living in primary care shortage
areas are at increased risk of preventable hospitalizations. Preventable disease
hospitalizations increase for all subgroups, except white/non-Hispanic children,
as neighborhoods became more racially diverse. CONCLUSIONS: Understanding the
geographic distribution of disease and impact of individual and community level
factors is essential to expanding access to care and preventive resources to
improve the health of children in California's most polluted and underserved
region.
PMID- 26421488
TI - Preparing Pediatric Patients for Adult Care: Are We Ready?
PMID- 26421489
TI - The Challenges of Adolescence, Mood Disorders, and Chronic Illness.
PMID- 26421490
TI - Recent advances in genomics and transcriptomics of cnidarians.
AB - The advent of the genomic era has provided important and surprising insights into
the deducted genetic composition of the common ancestor of cnidarians and
bilaterians. This has changed our view of how genomes of metazoans evolve and
when crucial gene families arose and diverged in animal evolution. Sequencing of
several cnidarian genomes showed that cnidarians share a great part of their gene
repertoire as well as genome synteny with vertebrates, with less gene losses in
the anthozoan cnidarian lineage than for example in ecdysozoans like Drosophila
melanogaster or Caenorhabditis elegans. The Hydra genome on the other hand has
evolved more rapidly indicated by more divergent sequences, more cases of gene
losses and many taxonomically restricted genes. Cnidarian genomes also contain a
rich repertoire of transcription factors, including those that in bilaterian
model organisms regulate the development of key bilaterian traits such as
mesoderm, nervous system development and bilaterality. The sea anemone
Nematostella vectensis, and possibly cnidarians in general, does not only share
its complex gene repertoire with bilaterians, but also the regulation of crucial
developmental regulatory genes via distal enhancer elements. In addition,
epigenetic modifications on DNA and chromatin are shared among eumetazoans. This
suggests that most conserved genes present in our genomes today, as well as the
mechanisms guiding their expression, evolved before the divergence of cnidarians
and bilaterians about 600 Myr ago.
PMID- 26421491
TI - Effects of CYP3A4/5 and ABCB1 genetic polymorphisms on carbamazepine metabolism
and transport in Chinese patients with epilepsy treated with carbamazepine in
monotherapy and bitherapy.
AB - OBJECTIVE: To examine the effects of cytochrome P450 3A4 (CYP3A4), cytochrome
P450 3A5 (CYP3A5) and ATP-binding cassette sub-family B member 1 (ABCB1) genetic
polymorphisms on carbamazepine (CBZ) plasma concentrations in Chinese patients
with epilepsy using CBZ as monotherapy and bitherapy with phenytoin (PHT),
phenobarbital (PB), or valproic acid (VPA). METHODS: Eighty-eight Chinese
patients with epilepsy were recruited from Xiangya Hospital Central South
University, of whom 66 patients were placed in the CBZ monotherapy group, 10
patients were placed in the CBZ bitherapy group combined with one enzyme-inducing
anti-seizure medications (PHT or PB), and 12 patients were placed in the CBZ
bitherapy group combined with VPA. Carbamazepine and carbamazepine-10,11-epoxide
(CBZ-E) plasma concentration of these patients were measured. In addition, the
genetic polymorphisms of rs4646440 and rs2242480 in the CYP3A4 gene, rs15524 and
rs776746 in the CYP3A5 gene, and rs1045642, rs2032582, rs10234411 and rs1128503
in the ABCB1 gene of the cohort were genotyped. Subsequently, the associations
between CBZ plasma concentrations and target single-nucleotide polymorphisms
(SNPs), as well as haplotypes, were analysed. RESULTS: In the CBZ monotherapy
group, dose-adjusted CBZ concentrations were not associated with the eight SNPs
and haplotypes. In the CBZ+PHT/PB group, rs776746, rs15524 and rs15524-rs776746
GT, AC haplotype were significantly associated with dose-adjusted CBZ plasma
concentration (P=0.006, 0.006, 0.003, 0.003, respectively) and CBZ plus CBZ-E
concentrations (P=0.006, 0.006, 0.006, 0.006, respectively); rs2032582,
rs10234411 and rs2032582-rs10234411 AT, and CA haplotype were associated with the
CBZ-E/CBZ ratio (P=0.007, 0.004, 0.004, 0.007, respectively). CONCLUSIONS:
rs776746 and rs15524 in the CYP3A5 gene tend to affect CBZ metabolism, and
rs2032582, rs10234411 in the ABCB1 gene may contribute to inter-individual
variation in CBZ and in CBZ-E transport among patients with epilepsy using CBZ in
combination with PHT or PB.
PMID- 26421492
TI - Machine learning classification of mesial temporal sclerosis in epilepsy
patients.
AB - BACKGROUND AND PURPOSE: Novel approaches applying machine-learning methods to
neuroimaging data seek to develop individualized measures that will aid in the
diagnosis and treatment of brain-based disorders such as temporal lobe epilepsy
(TLE). Using a large cohort of epilepsy patients with and without mesial temporal
sclerosis (MTS), we sought to automatically classify MTS using measures of
cortical morphology, and to further relate classification probabilities to
measures of disease burden. MATERIALS AND METHODS: Our sample consisted of high
resolution T1 structural scans of 169 adults with epilepsy collected across five
different 1.5T and four different 3T scanners at UCLA. We applied a multiple
support vector machine recursive feature elimination algorithm to morphological
measures generated from FreeSurfer's automated segmentation and parcellation in
order to classify Epilepsy patients with MTS (n=85) from those without MTS
(N=84). RESULTS: In addition to hippocampal volume, we found that alterations in
cortical thickness, surface area, volume and curvature in inferior frontal and
anterior and inferior temporal regions contributed to a classification accuracy
of up to 81% (p=1.3*10(-17)) in identifying MTS. We also found that MTS
classification probabilities were associated with a longer duration of disease
for epilepsy patients both with and without MTS. CONCLUSIONS: In addition to
implicating extra-hippocampal involvement of MTS, these findings shed further
light on the pathogenesis of TLE and may ultimately assist in the development of
automated tools that incorporate multiple neuroimaging measures to assist
clinicians in detecting more subtle cases of TLE and MTS.
PMID- 26421493
TI - Evaluation of multiple putative risk alleles within the 15q13.3 region for
genetic generalized epilepsy.
AB - The chromosome 15q13.3 region has been implicated in epilepsy, intellectual
disability and neuropsychiatric disorders, especially schizophrenia. Deficiency
of the acetylcholine receptor gene CHRNA7 and the partial duplication, CHRFAM7A,
may contribute to these phenotypes and we sought to comprehensively analyze these
genes in genetic generalized epilepsy. We analyzed using DHPLC, Sanger sequencing
and long range PCR, 174 probands with genetic generalized epilepsy with or
without intellectual disability or psychosis, including 8 with the recurrent
15q13.3 microdeletion. We searched CHRNA7 and CHRFAM7A for single sequence
variants, small copy number variants, and the common 2-bp deletion in CHRFAM7A.
We identified two novel and one reported missense variants. The common 2-bp
deletion was not enriched in patients compared to controls. Our data suggest that
missense mutations in CHRNA7 contribute to complex inheritance in genetic
generalized epilepsy in a similar fashion to the 15q13.3 microdeletion. They do
not support a pathogenic role for the common 2-bp CHRFAM7A deletion.
PMID- 26421494
TI - A "turn-on" fluorescent chemosensor for aluminum ion and cell imaging
application.
AB - A simple and efficient fluorescent chemosensor for Al(3+) is reported in the
paper. The chemosensor is obtained by dehydration reaction of 2-hydroxy-1
naphthaldehyde and 2-aminophenol. The chemosensor has high selectivity and
sensitivity for Al(3+) and displays fluorescence "off-on" switch signal. The
detection limit of the chemosensor for Al(3+) can reach 1.0*10(-7) M in DMSO/H2O
(1:9, v/v) solution. The mass spectra and Job's plot analysis confirm the 1:1
stoichiometry between chemosensor and Al(3+). Potential utilization of the probe
as an intracellular sensor of Al(3+) in human cancer (HiSa) cells is also
examined by confocal fluorescence microscopy.
PMID- 26421495
TI - Tyrosyl-DNA-phosphodiesterase I (TDP1) participates in the removal and repair of
stabilized-Top2alpha cleavage complexes in human cells.
AB - Tyrosyl-DNA-phosphodiesterase 1 (TDP1) is a DNA repair enzyme that removes
irreversible protein-linked 3' DNA complexes, 3' phosphoglycolates, alkylation
damage-induced DNA breaks, and 3' deoxyribose nucleosides. In addition to its
extended spectrum of substrates, TDP1 interacts with several DNA damage response
factors. To determine whether TDP1 participates in the repair of topoisomerase II
(Top2) induced DNA lesions, we generated TDP1 depleted (TDP1kd) human tumoral
cells. We found that TDP1kd cells are hypersensitive to etoposide (ETO).
Moreover, we established in a chromatin context that following treatment with
ETO, TDP1kd cells accumulate increased amounts of Top2alpha cleavage complexes,
removing them with an altered kinetics. We also showed that TDP1 depleted cells
accumulate increased gammaH2AX and pS296Chk1 signals following treatment with
ETO. Similarly, cytogenetics analyses following Top2 poisoning revealed increased
amounts of chromatid and chromosome breaks and exchanges on TDP1kd cells in the
presence or not of the DNA-PKcs inhibitor NU7026. However, the levels of sister
chromatid exchanges were similar in both TDP1kd and control non-silenced cell
lines. This suggests a role of TDP1 in both canonical non-homologous end joining
and alternative end joining, but not in the homologous recombination repair
pathway. Finally, micronucleus analyses following ETO treatment revealed a higher
frequency of micronucleus containing gammaH2AX signals on TDP1kd cells. Together,
our results highlight an active role of TDP1 in the repair of Top2-induced DNA
damage and its relevance on the genome stability maintenance in human cells.
PMID- 26421496
TI - Twenty-Seven-Year Experience With the St. Jude Medical Biocor Bioprosthesis in
the Aortic Position.
AB - BACKGROUND: The aim of this study was to evaluate the long-term performance of
the St. Jude Medical Biocor porcine stented bioprosthesis in the aortic position.
METHODS: From January 1985 to December 1996, 455 patients underwent aortic valve
replacement with the St. Jude Medical Biocor prosthesis at the German Heart
Center Munich. Mean age at time of operation was 72.5 +/- 9 years. In all, 172
patients (37.8%) underwent concomitant coronary artery bypass grafting and 20
patients (4.4%) had had previous cardiac surgery. Event-free rates are given as
mean +/- SD. Adverse events were recorded according to the guidelines for
reporting morbidity and mortality after cardiac valvular operations. RESULTS:
Follow-up was complete in 93.4%. Mean follow-up time was 8.4 +/- 5.6 years, with
a total of 3,834 patient-years and a maximum of 27.4 years. Thirty patients were
lost to follow-up after a mean of 9.2 +/- 4.1 years. Overall survival rate at 10
and 15 years was 43.3% +/- 2.4% and 19.2% +/- 2.0%, respectively. Freedom from
structural valve deterioration at 10 and 15 years was 92.1% +/- 1.7% and 84.8% +/
3.0%, respectively. Freedom from valve-related reoperation at 10 and 15 years
was 90.6 +/- 1.7% and 86.3 +/- 2.5%, respectively. Twenty-four patients needed
reoperation for structural valve deterioration, 9 patients for endocarditis, 3
patients for paravalvular leakage, and 2 patients for aortic root aneurysm. At 15
years, freedom from major bleeding was 91.0% +/- 2.0% and freedom from
thromboembolism was 72.2% +/- 2.8%. CONCLUSIONS: This study represents the
longest follow-up for the St. Jude Medical Biocor prosthesis and shows an
excellent durability with a low incidence of valve-related complications.
PMID- 26421497
TI - Energetic and topological determinants of a phosphorylation-induced disorder-to
order protein conformational switch.
AB - We show that the phosphorylation of 4E-BP2 acts as a triggering event to shape
its folding-function landscape that is delicately balanced between conflicting
favorable energetics and intrinsically unfavorable topological connectivity. We
further provide first evidence that the fitness landscapes of proteins at the
threshold of disorder can differ considerably from ordered domains.
PMID- 26421498
TI - Efficacy of laparoscopically assisted high ligation of patent processus vaginalis
in children.
AB - INTRODUCTION: Laparoscopic hernia repairs have been proven to be efficient and
safe for children, despite the slightly higher recurrence rate compared with the
classic surgical repair. They have the advantage of easy and precise
identification of the type of defect and its correction, both in ipsilateral and
contralateral sides. OBJECTIVES: The objectives of this study were to evaluate
the efficacy, safety and outcome of the laparoscopically assisted piecemeal high
ligation of a patent processus vaginalis (PPV) in children. METHODS: A total of
40 children were enrolled into this prospective study; they were aged >= 6 months
and had an inguinal hernia. The peritoneal cavity, including the contralateral
side, was inspected for the possibility of bilateral hernias using a 3-mm 30
degrees telescope. Another 3-mm port was introduced through the same infra
umbilical incision. The hernia was manually reduced or with the aid of a working
infra-umbilical grasper. A prolene or vicryl 2/0 or 3/0 suture on a curved
semicircle round-bodied taper-ended 25-30 mm needle was introduced through a very
small inguinal skin-crease incision. It was passed through the abdominal wall
layers to the peritoneum and was manipulated by the laparoscopic grasper to pick
up the peritoneum in piecemeal all around the internal ring. The needle was then
pushed to the outside near to the entrance site, thus forming a semicircle around
the internal ring. The suture was then tied and the knot was subcutaneously
buried. The primary outcome of the procedure was the incidence of intraoperative
diagnosis and surgical repair of contralateral hernias in pre-operatively
diagnosed unilateral cases. The secondary outcomes were defined as the incidence
of complications and hernia recurrence. RESULTS: DISCUSSION: The exploratory
laparoscopy found contralateral patent processus vaginalis (CPPV) with a
detection rate of 28.1%. Chan et al., Esposito et al., Toufique et al. and Niyogi
et al. reported similar figures for laparoscopic contralateral hernia detection
rates of 28%, 39%, 39.7% and 29.2%, respectively. The limitations of this study
were the small sample size, plus the risk factors and clinical significance for
CPPV. CONCLUSION: Laparascopically assisted piecemeal closure of the internal
inguinal ring in children is a safe and effective procedure. It helps in
detecting a contralateral hernia without prolonging the operative time.
PMID- 26421499
TI - Implications of a Biosignature Study of the Placebo Response in Major Depressive
Disorder.
PMID- 26421500
TI - Distinct Packings of Supramolecular Building Blocks in Metal-Organic Frameworks
Based on Imidazoledicarboxylic Acid.
AB - When the supramolecular building block packings (face-centered, body-centered,
and primitive cubic) with different interactions (hydrogen and coordination
bonding) were controlled, four new structures based on octahedral M(II) (M = Zn,
Ni, Mn) and imidazoledicarboxylate were constructed. The interaction modes
between the supramolecular building blocks affect the water stability of the
structures. Furthermore, with uncoordinated carboxylate O atoms in the
structures, these compounds demonstrate a strong capability of capturing metal
ions in the solution.
PMID- 26421502
TI - Detection of thiocyanate through limiting growth of AuNPs with C-dots acting as
reductant.
AB - We have found that hydroxyl-rich carbon dots (C-dots) have the ability to reduce
Au(3+) to form gold nanoparticles (AuNPs). Thiocyanate (SCN(-)) can be absorbed
on the surface of the AuNPs due to its high affinity toward the AuNPs, which
inhibits the growth of the AuNPs. Meanwhile, SCN(-) has the ability to etch the
as-synthesized big AuNPs to small AuNPs, which can also cause the absorption peak
of the AuNPs to decrease. Therefore, an optical sensor is developed for the
detection of SCN(-) based on measuring the plasmon resonance absorption peak
change of the AuNPs. Under optimal conditions, this method yields excellent
sensitivity (the limit of detection is 0.16 MUM) and selectivity toward SCN(-).
This method can detect SCN(-) in raw milk with satisfactory results. This work
gives new insight into monitoring the quality of milk.
PMID- 26421501
TI - The Recognition of Identical Ligands by Unrelated Proteins.
AB - The binding of drugs and reagents to off-targets is well-known. Whereas many off
targets are related to the primary target by sequence and fold, many ligands bind
to unrelated pairs of proteins, and these are harder to anticipate. If the
binding site in the off-target can be related to that of the primary target, this
challenge resolves into aligning the two pockets. However, other cases are
possible: the ligand might interact with entirely different residues and
environments in the off-target, or wholly different ligand atoms may be
implicated in the two complexes. To investigate these scenarios at atomic
resolution, the structures of 59 ligands in 116 complexes (62 pairs in total),
where the protein pairs were unrelated by fold but bound an identical ligand,
were examined. In almost half of the pairs, the ligand interacted with unrelated
residues in the two proteins (29 pairs), and in 14 of the pairs wholly different
ligand moieties were implicated in each complex. Even in those 19 pairs of
complexes that presented similar environments to the ligand, ligand superposition
rarely resulted in the overlap of related residues. There appears to be no single
pattern-matching "code" for identifying binding sites in unrelated proteins that
bind identical ligands, though modeling suggests that there might be a limited
number of different patterns that suffice to recognize different ligand
functional groups.
PMID- 26421503
TI - Evidence-Based Clinical Prevention in the Era of the Patient Protection and
Affordable Care Act: The Role of the US Preventive Services Task Force.
PMID- 26421504
TI - Performance Enhancement of Dye-Sensitized Solar Cells Based on TiO2 Thick
Mesoporous Photoanodes by Morphological Manipulation.
AB - This study is an attempt to give an account of the preparation of mesoporous TiO2
thick templated films of nonsimilar pore architecture and their use in dye
sensitized solar cells (DSSCs). Highly crystallized mesoporous titania thick
templated films with four different morphologies including hexagonal, wormlike,
cubic, and gridlike mesostructure, have been successfully synthesized through an
evaporation-induced self-assembly (EISA) route followed by layer-by-layer
deposition. Stabilization, followed by each coating, and calcinations, carried
out after every five layers, were used to produce crack-free thick films. These
mesoporous templated titanium dioxide samples were characterized by TEM, XRD,
SEM, BET, and UV-vis measurements and used as a photoelectrode material in DSSCs.
The mesostructured films with a thickness of about 7 MUm demonstrated better
performance in comparison to nanocrystalline TiO2 films (NC-TiO2) at a film
thickness of 13 MUm as the most typical films utilized in DSSCs. The findings
reveal that a surfactant/Ti ratio change undergone for developing cubic
mesostructures can enhance the crystallinity and roughness factor and therefore
increase the energy conversion efficiency of DSSC. The cell performances derived
from these mesofilms were enhanced compared to the efficiencies reported thus
far. The best photovoltaic performance of 8.73% came from DSSC using the cubic
mesoporous TiO2 photoelectrode with the following properties: open circuit
voltage of 743 mV, short circuit photocurrent density of 16.35 mA/cm(2), and fill
factor of 0.72.
PMID- 26421505
TI - Carrier Recombination Dynamics in Sulfur-Doped InP Nanowires.
AB - Measuring lifetime of photogenerated charges in semiconductor nanowires (NW) is
important for understanding light-induced processes in these materials and is
relevant for their photovoltaic and photodetector applications. In this paper, we
investigate the dynamics of photogenerated charge carriers in a series of as
grown InP NW with different levels of sulfur (S) doping. We observe that
photoluminescence (PL) decay time as well as integrated PL intensity decreases
with increasing S doping. We attribute these observations to hole trapping with
the trap density increased due to S-doping level followed by nonradiative
recombination of trapped charges. This assignment is proven by observation of the
trap saturation in three independent experiments: via excitation power and
repetition rate PL lifetime dependencies and by PL pump-probe experiment.
PMID- 26421506
TI - Changes in fetal myocardial performance index following intravascular
transfusion: preliminary report.
AB - OBJECTIVE: To investigate the changes in fetal left ventricle myocardial
performance index (MPI) following intrauterine intravascular transfusion (IUT).
METHODS: Prospective study, including 25 IUT performed in 13 singleton
pregnancies with maternal Rh D alloimmune disease. Left ventricle MPI was
evaluated prior to transfusion and repeated 24 h after each procedure. Delta MPI
was calculated as the difference between post- and pre-transfusion MPI z-scores.
Multilevel regression analysis was used to examine the association between delta
MPI and gestational age at procedure, fetal middle cerebral artery peak velocity
MoM, pre- and post-MPI and hemoglobin z-score values, the volume of blood
transfused and feto-placental volume percentage expansion. Adjustments were made
for repeated measurements within the same fetus, and across different time
points. The significance level was set as 0.05. RESULTS: MPI z-score values
increased significantly following transfusion (delta MPI = 1.10 +/- 2.47,
p=0.036). Delta MPI showed a significant correlation with gestational age at
transfusion (r= -0.47, p=0.018), pre-transfusion MPI z-score (r= -0.50, p=0.012)
and feto-placental volume percentage expansion (r= -0.41, p=0.044). CONCLUSION:
Left ventricle MPI increases significantly after intrauterine blood transfusion
and greater changes are associated with procedures at an earlier gestational age,
lower pre-transfusion MPI z-scores and smaller feto-placental volume expansion.
PMID- 26421507
TI - Detecting lateral composition modulation in dilute Ga(As,Bi) epilayers.
AB - The ability to characterize a structure into the finest details in a quantitative
manner is a key issue to understanding and controlling nanoscale phase separation
in novel nanomaterials. In this work, we consider the detectability of lateral
composition modulation (LCM), a type of nanoscale phase separation in GaAs(1
x)Bix epilayers, by x-ray diffraction (XRD). We show that the satellite peaks due
to LCM are hardly detectable in reasonable time with a lab x-ray diffractometer
for GaAs(1-x)Bix samples with an average x up to 25% and relative modulation up
to 50%. This is in contrast to LCM reported in other III-V combinations, where
the intensity of the satellite peak is relatively high and can be easily
detected. Our theoretical considerations are complemented experimentally using
highly brilliant synchrotron radiation. The results are in good agreement with
the predictions. This work provides a guideline for the systematic
characterization of LCM in zincblende III-V semiconductor epilayers and points to
the critical role of quantitative characterization of nanoscale phase separation.
PMID- 26421508
TI - Adult Daughters' Descriptions of Their Mother-Daughter Relationship in the
Context of Chronic Conflict.
AB - The purpose of this article is to describe, from the perspective of the adult
daughter, the mother-daughter relationship in the context of chronic conflict.
Grounded theory methodology was used. An online recruitment strategy was used to
identify a sample of adult daughters (N = 13) who self-identified as having an
abusive relationship with their aging mother. Data collection was completed
through semi-structured telephone interviews. Daughters framed their relationship
around their perceptions of past childhood injustices. These injustices invoked
strong negative emotions. Daughters had equally strong motivations for sustaining
the relationship, driven by desire to reconcile their negative experience through
seeking validation and futile-hoping as well as a sense of obligation to do due
diligence. Together these factors created an environment of inevitable
confrontation and a relationship defined by chronic conflict. Findings from the
study provide theoretical insights to the conceptualization of aggression, power
relationships, and the development of elder abuse and neglect.
PMID- 26421509
TI - The Genetics of Nitrogen Use Efficiency in Crop Plants.
AB - In the past 50 years, the application of synthetic nitrogen (N) fertilizer to
farmland resulted in a dramatic increase in crop yields but with considerable
negative impacts on the environment. New solutions are therefore needed to
simultaneously increase yields while maintaining, or preferably decreasing,
applied N to maximize the nitrogen use efficiency (NUE) of crops. In this review,
we outline the definition of NUE, the selection and development of NUE crops, and
the factors that interact with NUE. In particular, we emphasize the challenges of
developing crop plants with enhanced NUE, using more classical genetic approaches
based on utilizing existing allelic variation for NUE traits. The challenges of
phenotyping, mapping quantitative trait loci (QTLs), and selecting candidate
genes for NUE improvement are described. In addition, we highlight the importance
of different factors that lead to changes in the NUE components of nitrogen
uptake efficiency (NUpE) and nitrogen utilization efficiency (NUtE).
PMID- 26421510
TI - Centromere Associations in Meiotic Chromosome Pairing.
AB - Production of gametes of halved ploidy for sexual reproduction requires a
specialized cell division called meiosis. The fusion of two gametes restores the
original ploidy in the new generation, and meiosis thus stabilizes ploidy across
generations. To ensure balanced distribution of chromosomes, pairs of homologous
chromosomes (homologs) must recognize each other and pair in the first meiotic
division. Recombination plays a key role in this in most studied species, but it
is not the only actor and particular chromosomal regions are known to facilitate
the meiotic pairing of homologs. In this review, we focus on the roles of
centromeres and in particular on the clustering and pairwise associations of
nonhomologous centromeres that precede stable pairing between homologs. Although
details vary from species to species, it is becoming increasingly clear that
these associations play active roles in the meiotic chromosome pairing process,
analogous to those of the telomere bouquet.
PMID- 26421513
TI - Scaffolded Active Learning: Nine Pedagogical Principles for Building a Modern
Veterinary Curriculum.
AB - Veterinary discipline experts unfamiliar with the broader educational literature
can find the adoption of an evidence-based approach to curriculum development
challenging. However, greater societal and professional demands for achieving and
verifying Day One knowledge and skills, together with continued progress in
information generation and technology, make it all the more important that the
defined period for initial professional training be well used. This article
presents and discusses nine pedagogical principles that have been used in modern
curricular development in Australia, the United Kingdom, and the United States:
(1) outcomes-based curriculum design; (2) valid and reliable assessments; (3)
active learning; (4) integrated knowledge for action; (5) tightly controlled core
curriculum; (6) "just-in-time" rather than "just-in-case" knowledge; (7) vertical
integration, the spiral curriculum, and sequential skills development; (8)
learning skills support; and (9) bridges from classroom to workplace. Crucial to
effective educational progress is active learning that embraces the skills
required by the modern professional, made possible by tight control of curricular
content. In this information age, professionals' ability to source information on
a "just-in-time" basis to support high quality reasoning and decision making is
far more important than the memorization of large bodies of increasingly
redundant information on a "just-in-case" basis. It is important that those with
responsibility for veterinary curriculum design ensure that their programs fully
equip the modern veterinary professional for confident entry into the variety of
roles in which society needs their skills.
PMID- 26421511
TI - The Behavioral Definitions of "Having Sex With a Man" and "Having Sex With a
Woman" Identified by Women Who Have Engaged in Sexual Activity With Both Men and
Women.
AB - A sizable minority of women report lifetime sexual behavior with both men and
women. In the present study, a multinational sample of women who reported genital
contact with at least one man and one woman in their lifetime (N = 2,751) were
asked to provide their behavioral definitions of "having sex with a woman" and
"having sex with a man." Replicating previous research, participants were asked
"Would you say you 'had sex' with a woman/man if the most intimate behavior you
engaged in with her/him was ..." followed by a list of behaviors that differed
based on the hypothetical partner gender. While most participants indicated that
they would consider "having had sex" if they engaged in a variety of behaviors,
behaviors involving genital contact were most often included within the
participants' definitions of having sex, regardless of partner gender. The
percentage of behaviors included in the participants' definitions of having sex
with a woman (M = 59.40%, SD = 20.77%) was higher than the percentage of
behaviors included in their definition of having sex with a man (M = 37.26%, SD =
28.97%). Broadening our understanding of "having sex" for individuals with
diverse sexual experiences may have important implications for clinicians and
researchers.
PMID- 26421514
TI - Final-Year Students' and Clinical instructors' Experience of Workplace-Based
Assessments Used in a Small-Animal Primary-Veterinary-Care Clinical Rotation.
AB - Final-year veterinary students must meet baseline clinical competency upon
completion of their training for entry to practice. Workplace-based assessments
(WBAs), widely used in human medical training to assess post-graduate students'
professionalism and clinical performance, have recently been adopted in
undergraduate veterinary clinical teaching environments. WBAs should support
veterinary trainees' learning in a clinical teaching environment, though utility
of WBAs within veterinary education may differ from that in medical training due
to differences in context and in learners' stage of clinical development. We
conducted focus groups with final-year veterinary students and clinical
instructors following the implementation of three WBAs (Direct Observation of
Procedural Skills [DOPS], the Mini-Clinical evaluation exercise [Mini-CEX], and
the In-Training Evaluation Report [ITER]) during a small-animal primary
veterinary-care rotation. Students and clinical instructors viewed the DOPS and
Mini-CEX as feasible and valuable learning and assessment tools that offered an
overall opportunity for timely in-the-moment feedback. Instructors viewed the
ITER as less feasible in the context of a service-oriented veterinary clinical
teaching environment. Students believed the ITER had potential to be informative,
although in its existing application the ITER had limited utility due to time
constraints on instructors that prevented them from providing students with
individualized and specific feedback. In service-oriented veterinary clinical
teaching environments, successful implementation of WBAs requires balancing
provision of feedback to students, time demands on clinical instructors, and
flexibility of assessment tools.
PMID- 26421515
TI - Clients and Veterinarians as Partners in Problem Solving during Cancer
Management: Implications for Veterinary Education.
AB - This research explores client satisfaction with veterinarian interactions and
support during cancer management. Ninety-four members of the online Pet Cancer
Support group completed the electronic communication and support questionnaire.
Results show that 77% of respondents (n=72) are satisfied with their
veterinarian; 71% (n=67) are satisfied with the information their veterinarian
provides about treatment options; and 70% percent (n=66) are satisfied with the
support they receive from their veterinarian. Strong, positive correlations exist
between level of satisfaction and information about treatment options (rs=.795,
n=91, p<.001) and between level of satisfaction and support received from the
veterinarian (rs=.759, n=90, p<.001). Problem-focused informational support and
tangible support dominated clients' descriptions of support and affected their
support satisfaction. Emotion-focused support was not as important, and in some
cases was not expected of the veterinarian. Results suggested that clients'
overall satisfaction with their veterinarian is related to their satisfaction
with information about treatment options and satisfaction with the support the
veterinarian provides. By providing problem-focused support, veterinarians can
empower clients and enhance their sense of control, thus positively affecting
satisfaction and the likelihood of a long-lasting relationship. Taken together,
these findings have implications for our understanding of veterinarian-client
communication related to relationship-centered care and client empowerment, as
well as implications for veterinary medical education and communication
curricula.
PMID- 26421516
TI - Closing the Loop: Using Evidence to Inform Refinements to an Admissions Process.
AB - Substantive changes in our evaluation of applicants have been implemented in
response to the findings of the various phases of outcomes assessment. This
article will describe the changes that have been implemented as a result of
analyzing the association of pre-veterinary academic, subjective, and behavioral
event interview scores with veterinary students' performance in the DVM program,
including clinical competencies, and their performance on the North American
Veterinary Licensing Examination. Pre-veterinary academic performance predicted
academic performance in veterinary school. Subjective measures did not, and we
have reduced the faculty workload associated with that part of the evaluation of
applicants. Interview scores provide additional but small value in predicting
performance on clinical competencies.
PMID- 26421517
TI - Monitoring the Veterinary Medical Student Experience: An Institutional Pilot
Study.
AB - Veterinary medical school challenges students academically and personally, and
some students report depression and anxiety at rates higher than the general
population and other medical students. This study describes changes in veterinary
medical student self-esteem (SE) over four years of professional education,
attending to differences between high and low SE students and the characteristics
specific to low SE veterinary medical students. The study population was students
enrolled at the Michigan State University College of Veterinary Medicine from
2006 to 2012. We used data from the annual anonymous survey administered college
wide that is used to monitor the curriculum and learning environment. The survey
asked respondents to rate their knowledge and skill development, learning
environment, perceptions of stress, skill development, and SE. Participants also
provided information on their academic performance and demographics. A
contrasting groups design was used: high and low SE students were compared using
logistic regression to identify factors associated with low SE. A total of 1,653
respondents met inclusion criteria: 789 low SE and 864 high SE students. The
proportion of high and low SE students varied over time, with the greatest
proportion of low SE students during the second-year of the program. Perceived
stress was associated with low SE, whereas perceived supportive learning
environment and skill development were associated with high SE. These data have
provided impetus for curricular and learning environment changes to enhance
student support. They also provide guidance for additional research to better
understand various student academic trajectories and their implications for
success.
PMID- 26421518
TI - Zebrafish Database: Customizable, Free, and Open-Source Solution for Facility
Management.
AB - Zebrafish Database is a web-based customizable database solution, which can be
easily adapted to serve both single laboratories and facilities housing thousands
of zebrafish lines. The database allows the users to keep track of details
regarding the various genomic features, zebrafish lines, zebrafish batches, and
their respective locations. Advanced search and reporting options are available.
Unique features are the ability to upload files and images that are associated
with the respective records and an integrated calendar component that supports
multiple calendars and categories. Built on the basis of the Joomla content
management system, the Zebrafish Database is easily extendable without the need
for advanced programming skills.
PMID- 26421519
TI - S-Nitrosylation of Sarcomeric Proteins Depresses Myofilament Ca2+)Sensitivity in
Intact Cardiomyocytes.
AB - AIMS: The heart responds to physiological and pathophysiological stress factors
by increasing its production of nitric oxide (NO), which reacts with
intracellular glutathione to form S-nitrosoglutathione (GSNO), a protein S
nitrosylating agent. Although S-nitrosylation protects some cardiac proteins
against oxidative stress, direct effects on myofilament performance are unknown.
We hypothesize that S-nitrosylation of sarcomeric proteins will modulate the
performance of cardiac myofilaments. RESULTS: Incubation of intact mouse
cardiomyocytes with S-nitrosocysteine (CysNO, a cell-permeable low-molecular
weight nitrosothiol) significantly decreased myofilament Ca(2+) sensitivity. In
demembranated (skinned) fibers, S-nitrosylation with 1 MUM GSNO also decreased
Ca(2+) sensitivity of contraction and 10 MUM reduced maximal isometric force,
while inhibition of relaxation and myofibrillar ATPase required higher
concentrations (>= 100 MUM). Reducing S-nitrosylation with ascorbate partially
reversed the effects on Ca(2+) sensitivity and ATPase activity. In live
cardiomyocytes treated with CysNO, resin-assisted capture of S-nitrosylated
protein thiols was combined with label-free liquid chromatography-tandem mass
spectrometry to quantify S-nitrosylation and determine the susceptible cysteine
sites on myosin, actin, myosin-binding protein C, troponin C and I, tropomyosin,
and titin. The ability of sarcomere proteins to form S-NO from 10-500 MUM CysNO
in intact cardiomyocytes was further determined by immunoblot, with actin,
myosin, myosin-binding protein C, and troponin C being the more susceptible
sarcomeric proteins. INNOVATION AND CONCLUSIONS: Thus, specific physiological
effects are associated with S-nitrosylation of a limited number of cysteine
residues in sarcomeric proteins, which also offer potential targets for
interventions in pathophysiological situations.
PMID- 26421520
TI - Dual expression of MYC and BCL2 proteins predicts worse outcomes in diffuse large
B-cell lymphoma.
AB - Recent studies suggested that MYC and BCL2 protein co-expression is an
independent indicator of poor prognosis in diffuse large B-cell lymphoma.
However, the immunohistochemistry protocols for dual-expression staining and the
scoring cut-offs vary by study. Sixty-nine cases of diffuse large B-cell lymphoma
were evaluated for MYC and BCL2 protein expression using various cut-offs that
have been recommended in prior studies. Independent of the International
Prognostic Index risk group, cases with dual protein expression of BCL2 and MYC
using >=50%/40% cut-offs and >=70%/40% had significantly shorter overall survival
than cases without. It was verified in this patient population that the use of
BCL2 and MYC immunohistochemistry, performed with available in vitro diagnostic
cleared antibodies, provides rapid prognostic information in patients with de
novo diffuse large B-cell lymphoma. This study has practical implications for
diagnostic laboratories and serves as a guide for implementation in the setting
of future clinical trials.
PMID- 26421521
TI - Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patients with
Traumatic Brain Injury Is Dependent on Baseline Cerebral Lactate/Pyruvate Ratio.
AB - Energy dysfunction is associated with worse prognosis after traumatic brain
injury (TBI). Recent data suggest that hypertonic sodium lactate infusion (HL)
improves energy metabolism after TBI. Here, we specifically examined whether the
efficacy of HL (3h infusion, 30-40 MUmol/kg/min) in improving brain energetics
(using cerebral microdialysis [CMD] glucose as a main therapeutic end-point) was
dependent on baseline cerebral metabolic state (assessed by CMD lactate/pyruvate
ratio [LPR]) and cerebral blood flow (CBF, measured with perfusion computed
tomography [PCT]). Using a prospective cohort of 24 severe TBI patients, we found
CMD glucose increase during HL was significant only in the subgroup of patients
with elevated CMD LPR >25 (n = 13; +0.13 [95% confidence interval (CI) 0.08-0.19]
mmol/L, p < 0.001; vs. +0.04 [-0.05-0.13] in those with normal LPR, p = 0.33,
mixed-effects model). In contrast, CMD glucose increase was independent from
baseline CBF (coefficient +0.13 [0.04-0.21] mmol/L when global CBF was <32.5
mL/100 g/min vs. +0.09 [0.04-0.14] mmol/L at normal CBF, both p < 0.005) and
systemic glucose. Our data suggest that improvement of brain energetics upon HL
seems predominantly dependent on baseline cerebral metabolic state and support
the concept that CMD LPR - rather than CBF - could be used as a diagnostic
indication for systemic lactate supplementation following TBI.
PMID- 26421523
TI - A One-Two Punch to Bone: Assessing the Combined Impact of Lead and a High-Fat
Diet.
PMID- 26421522
TI - Low-Intensity Pulsed Ultrasound Stimulation Enhances Heat-Shock Protein 90 and
Mineralized Nodule Formation in Mouse Calvaria-Derived Osteoblasts.
AB - Low-intensity pulsed ultrasound (LIPUS) has demonstrated its positive effects on
osteogenic differentiation of mesenchymal stem cells and the proliferation and
differentiation of osteoblasts, negative effects on osteoclast growth, and
promotion of angiogenesis, leading to improvement of the tissue perfusion. Heat
shock proteins (HSPs) are initially identified as molecules encouraged and
expressed by heat stress or chemical stress to cells and involved in the balance
between differentiation and apoptosis of osteoblasts. However, it remains unclear
if the effect of LIPUS on osteoblast differentiation could involve HSP expression
and contribution. In this study, mouse calvarial osteoblasts were exposed to
LIPUS at a frequency of 3.0 MHz by 30 mW/cm(2) for 15 min or to 42 degrees C heat
shock for 20 min at day 3 of cell culture and examined for osteogenesis with
pursuing induction of HSP27, HSP70, and HSP90. LIPUS as well as heat shock
initially upregulated HSP90 and phosphorylation of Smad1 and Smad5, encouraging
cell viability and proliferation at 24 h, enhancing mineralized nodule formation
stronger by LIPUS after 10 days. However, HSP27, associated with BMP2-stimulated
p38 mitogen-activated protein kinase during osteoblast differentiation, was
downregulated by both stimulations at this early time point. Notably, these two
stimuli maintained Smad1 phosphorylation with mineralized nodule formation even
under BMP2 signal blockage. Therefore, LIPUS might be a novel inducer of
osteoblastic differentiation through a noncanonical signal pathway. In
conclusion, LIPUS stimulation enhanced cell viability and proliferation as early
as 24 h after treatment, and HSP90 was upregulated, leading to dense
mineralization in the osteoblast cell culture after 10 days.
PMID- 26421524
TI - Interface Promoted Reversible Mg Insertion in Nanostructured Tin-Antimony Alloys.
AB - An interface promoted approach is developed for guiding the design of stable and
high capacity materials for Mg batteries using SnSb alloys as model materials.
Experimental and theoretical studies reveal that the SnSb alloy has exceptionally
high reversible capacity (420 mA h g(-1)), excellent rate capability, and good
cyclic stability for hosting Mg ions due to the stabilization/promotion effects
of the interfaces between the multicomponent phases generated during repeated
magnesiation-demagnesiation.
PMID- 26421526
TI - Retrieval of the equivalent acoustic constitutive parameters of an inhomogeneous
fluid-like object by nonlinear full waveform inversion.
AB - This study addresses the problem of the acoustic characterization of an
inhomogeneous object such as a soft-tissue organ containing a cyst or tumor whose
size and/or composition evolve either negatively due to increased disease or
positively due to increased response to treatment. The so-called 'corrupted'
binary object, probed by a transient, acoustic plane wave, is a tube composed of
a homogenous fluid-like (or assumed as such) mantle (medium 1: three acoustic
constitutive parameters, one geometric parameter) surrounding a homogeneous fluid
like (or assumed as such) core (medium 2: three acoustic constitutive parameters,
one geometric parameter), immersed in a spatially-infinite, homogeneous fluid
(host medium 0: two acoustic parameters). The complete inversion of the
diffracted acoustic field response of this object involves the retrieval of seven
(six acoustic and one geometric) parameters, assuming we know beforehand the
outer radius of the tube and acoustic parameters of the host. An alternative to
this time-consuming, hazardous (due to the ill-posed nature of the) procedure, is
to minimize the discrepancy, between the full waveform response of the binary
object to a transient plane wave and the response of a homogeneous cylinder
(medium characterized by three acoustic parameters, one geometric parameter) to
the same transient plane wave, so as to retrieve the (three so-called equivalent)
acoustic parameters of the homogeneous object. Thus, the first inverse problem is
replaced by a second one (same assumptions concerning the outer radius of the
objects, the host medium, the probe radiation and the sensing configuration as
the first one) involving the retrieval of only three (instead of six) acoustic
parameters. This procedure is potentially useful if the variation of at least one
of the three equivalent parameters is sensitive to the variation of a key
parameter of the inhomogeneous body (usually the characteristic dimension or the
wavespeed of the core) and this variation can be expressed in a simple algebraic
form (such as by a mixing formula). It is shown that this situation can arise if
the average frequency of the acoustic probe radiation is sufficiently low. A
sidelight of this investigation is the discovery that the equivalent constitutive
parameters of the homogeneous cylinder are dispersive even when the component
materials of the tube are not dispersive.
PMID- 26421525
TI - Effect of low-intensity laser treatment on pain after extraction of impacted
mandibular third molars: a randomised, controlled, clinical trial.
AB - Extraction of impacted third molars is painful, so we have evaluated whether low
intensity laser could reduce the pain. Sixty patients were randomly allocated to
five groups that were treated with laser immediately after extraction.
Postoperative pain was evaluated after two and seven days. The Shapiro-Wilk test
was used to assess whether the distribution was normal, and as it was skewed, the
Kruskal-Wallis test, ANOVA and the Student-Newman-Keuls test for multiple
comparisons were used to compare the groups. The Wilcoxon test was used for
comparisons of pain (measured by visual analogue scale (VAS) and numerical rating
scale (NRS) 101 between the second and seventh postoperative days). Probabilities
of less than 0.05 were accepted as significant. We conclude that a single session
of low intensity laser had no significant effect on the amount of pain under the
conditions investigated.
PMID- 26421527
TI - Spatiotemporal Changes of Built-Up Land Expansion and Carbon Emissions Caused by
the Chinese Construction Industry.
AB - China is undergoing rapid urbanization, enlarging the construction industry,
greatly expanding built-up land, and generating substantial carbon emissions. We
calculated both the direct and indirect carbon emissions from energy consumption
(anthropogenic emissions) in the construction sector and analyzed built-up land
expansion and carbon storage losses from the terrestrial ecosystem. According to
our study, the total anthropogenic carbon emissions from the construction sector
increased from 3,905*10(4) to 103,721.17*10(4) t from 1995 to 2010, representing
27.87%-34.31% of the total carbon emissions from energy consumption in China.
Indirect carbon emissions from other industrial sectors induced by the
construction sector represented approximately 97% of the total anthropogenic
carbon emissions of the sector. These emissions were mainly concentrated in seven
upstream industry sectors. Based on our assumptions, built-up land expansion
caused 3704.84*10(4) t of carbon storage loss from vegetation between 1995 and
2010. Cropland was the main built-up land expansion type across all regions. The
study shows great regional differences. Coastal regions showed dramatic built-up
land expansion, greater carbon storage losses from vegetation, and greater
anthropogenic carbon emissions. These regional differences were the most obvious
in East China followed by Midsouth China. These regions are under pressure for
strong carbon emissions reduction.
PMID- 26421528
TI - Prediction of susceptible biomarkers for end stage renal disease among North
Indians.
AB - AIM: Involvement of pro-inflammatory genes has been correlated with basic kidney
diseases and end stage renal disease (ESRD). However, results at odds were often
noted from such independent association studies. This study proposes a genome
wide analysis approach to predict ESRD risk associated genes. METHODS: We
included 42 single nucleotide polymorphisms (SNPs) showing association among
north Indian ESRD cases and controls. ESRD cases comprised chronic
glomerulonephritis (CGN), chronic interstitial nephritis (CIN), hypertension
(HTN) and autosomal dominant polycystic kidney disease (ADPKD). Genotyping data
obtained from our prior published reports were compared with Genome-Wide
Association Studies (GWAS) SNPs retrieved from HapMap and GWASCentral databases
using R-statistical package SNPAssoc. Linkage disequilibrium (LD), gene-gene
interaction, classification and regression tree (CART) and pathway analysis were
carried out in the present study supplemented with IL-6 and TNF-alpha levels
estimation using enzyme linked immunosorbent assay (ELISA). RESULTS: Comparison
of genotyping data with GWAS SNPs revealed significant associations for
interleukin (IL)1-RN, IL-6, MTHFR, tumour necrosis factor-alpha (TNF-alpha) and
CCR3 genes with ESRD. Nine SNPs were commonly associated with CGN, CIN, HTN,
ADPKD and ESRD. LD (D = 0.9) and gene-gene interaction (P = 0.0002) analyses
revealed significant associations for IL-6 and TNF-alpha genes. In a consistent
manner, CART analysis and functional analysis servers predict predisposing
effects for TNF-alpha and IL-6 with ESRD. Finally, higher body circulating levels
were observed for mutant TNF-alpha and IL-6 alleles among ESRD. CONCLUSION: The
study indicates significance for IL-6 and TNF-alpha gene with basic kidney
diseases and ESRD. Extensive statistical tests, pathway analysis and functional
assays also reflect attenuated level of significance for these SNPs. In future
these may be brought from bench side to clinical practice as diagnostic
biomarkers upon external and prospective replication and confirmation among other
cohorts.
PMID- 26421529
TI - A Solution-Processed Resonance Host for Highly Efficient Electrophosphorescent
Devices with Extremely Low Efficiency Roll-off.
AB - Solution-processible N-P=O resonance-host molecules are applied successfully in
spin-coated phosphorescent light-emitting diodes (PHOLEDs) to selectively and
self-adaptively tune the electrical properties for balanced charge
transportation. The resonance-molecule-hosted PHOLEDs exhibit a high maximum
quantum efficiency of 16.5% and a low efficiency roll-off down to 0.7%,
highlighting the significant progress of these solution-processed PHOLEDs with
high efficiency and flat efficiency roll-off achieved simultaneously.
PMID- 26421530
TI - Estimated Lifetime Medical and Work-Loss Costs of Fatal Injuries--United States,
2013.
AB - Injury-associated deaths have substantial economic consequences. In 2013,
unintentional injury was the fourth leading cause of death, suicide was the
tenth, and homicide was the sixteenth; these three causes accounted for
approximately 187,000 deaths in the United States. To assess the economic impact
of fatal injuries, CDC analyzed death data from the National Vital Statistics
System for 2013, along with cost of injury data using the Web-Based Injury
Statistics Query and Reporting System. This report updates a previous study that
analyzed death data from the year 2000, and employs recently revised methodology
for determining the costs of injury outcomes, which uses the most current
economic data and incorporates improvements for estimating medical costs
associated with injury. Number of deaths, crude and age-specific death rates, and
total lifetime work-loss costs and medical costs were calculated for fatal
injuries by sex, age group, intent (intentional versus unintentional), and
mechanism of injury. During 2013, the rate of fatal injury was 61.0 per 100,000
population, with combined medical and work-loss costs exceeding $214 billion.
Costs from fatal injuries represent approximately one third of the total $671
billion medical and work-loss costs associated with all injuries in 2013. The
magnitude of the economic burden associated with injury-associated deaths
underscores the need for effective prevention.
PMID- 26421531
TI - Babies, Bathwater, and Screening for Autism Spectrum Disorder: Comments on the
USPSTF Recommendations for Autism Spectrum Disorder Screening.
AB - Current guidelines for developmental screening and screening for autism spectrum
disorders (ASDs) recommend screening of all children for ASD at ages 18 and 24
months. In a draft recommendation, the United States Preventive Services Task
Force finds insufficient evidence to support this practice. Some of the
assumptions behind these recommendations fail to consider other benefits of
developmental surveillance and screening that ensue from periodic formal
screening of all children. Primary care clinicians should err on the side of
discovery and advocate for continued formal screening at designated intervals.
PMID- 26421532
TI - Dipyridamole stress myocardial perfusion by computed tomography in patients with
left bundle branch block.
AB - BACKGROUND: Functional tests have limited accuracy for identifying myocardial
ischemia in patients with left bundle branch block (LBBB). OBJECTIVE: To assess
the diagnostic accuracy of dipyridamole-stress myocardial computed tomography
perfusion (CTP) by 320-detector CT in patients with LBBB using invasive
quantitative coronary angiography (QCA) (stenosis >= 70%) as reference; to
investigate the advantage of adding CTP to coronary computed tomography
angiography (CTA) and compare the results with those of single photon emission
computed tomography (SPECT) myocardial perfusion scintigraphy. METHODS: Thirty
patients with LBBB who had undergone SPECT for the investigation of coronary
artery disease were referred for stress tomography. Independent examiners
performed per-patient and per-coronary territory assessments. All patients gave
written informed consent to participate in the study that was approved by the
institution's ethics committee. RESULTS: The patients' mean age was 62 +/- 10
years. The mean dose of radiation for the tomography protocol was 9.3 +/- 4.6
mSv. With regard to CTP, the per-patient values for sensitivity, specificity,
positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%,
and 83%, respectively (p = 0.001). The per-territory values were 63%, 86%, 65%,
84%, and 79%, respectively (p < 0.001). In both analyses, the addition of CTP to
CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than
SPECT (p < 0.001). CONCLUSION: The use of the stress tomography protocol is
feasible and has good diagnostic accuracy for assessing myocardial ischemia in
patients with LBBB.
PMID- 26421536
TI - 750 nm 1.5 W frequency-doubled semiconductor disk laser with a 44 nm tuning
range.
AB - We demonstrate 1.5 W of output power at the wavelength of 750 nm by intracavity
frequency doubling a wafer-fused semiconductor disk laser diode-pumped at 980 nm.
An optical-to-optical efficiency of 8.3% was achieved using a bismuth borate
crystal. The wavelength of the doubled emission could be tuned from 720 to 764 nm
with an intracavity birefringent plate. The beam quality parameter M2
of the laser output was measured to be below 1.5 at all pump powers. The laser is
a promising tool for biomedical applications that can take advantage of the large
penetration depth of light in tissue in the 700-800 nm spectral range.
PMID- 26421535
TI - Incidence and Predictors of Cardiovascular Complications and Death after Vascular
Surgery.
AB - BACKGROUND: Patients undergoing arterial vascular surgery are considered at
increased risk for post-operative complications. OBJECTIVE: To assess the
incidence and predictors of complications and death, as well as the performance
of two models of risk stratification, in vascular surgery. METHODS: This study
determined the incidence of cardiovascular complications and deaths within 30
days from surgery in adults. Univariate comparison and logistic regression
assessed the risk factors associated with the outcomes, and the receiver
operating characteristic (ROC) curve assessed the discriminatory capacity of the
revised cardiac risk index (RCRI) and vascular study group of New England cardiac
risk index (VSG-CRI). RESULTS: 141 patients (mean age, 66 years; 65% men)
underwent the following surgeries: carotid (15); lower limbs (65); abdominal
aorta (56); and others (5). Cardiovascular complications and death occurred
within 30 days in 28 (19.9%) and 20 (14.2%) patients, respectively. The risk
predictors were: age, obesity, stroke, poor functional capacity, altered
scintigraphy, surgery of the aorta, and troponin change. The scores RCRI and VSG
CRI had area under the curve of 0.635 and 0.639 for early cardiovascular
complications, and 0.562 and 0.610 for death in 30 days. CONCLUSION: In this
small and selected group of patients undergoing arterial vascular surgery, the
incidence of adverse events was elevated. The risk assessment indices RCRI and
VSG-CRI did not perform well for complications within 30 days.
PMID- 26421537
TI - High-resolution chalcogenide fiber bundles for infrared imaging.
AB - An ordered chalcogenide fiber bundle with a high resolution for infrared imaging
was fabricated using a stack-and-draw approach. The fiber bundle consisted of
about 810,000 single fibers with an As2S3 glass core of 9 MUm in diameter and a
polyetherimide (PEI) polymer cladding of 10 MUm in diameter. The As2S3/PEI fibers
showed good transparency in the 1.5-6.5 MUm spectral region. It presented a
resolution of ~45 lp/mm and a crosstalk of ~2.5%. Fine thermal images of a hot
soldering iron tip were delivered through the fiber bundle.
PMID- 26421538
TI - Critical-angle-based sensor with improved figure of merit using dip detection.
AB - It is demonstrated theoretically and experimentally that a one-dimensional
photonic crystal (1D-PC) made of quarter waves stacked on top of a prism exhibits
both TE and TM resonances that coincide with the critical angle theta(c) when the
1D-PC is semi-infinite and with very little deviation from theta(c) for a finite
1D-PC. As a refractive index (RI) sensor, it behaves as a total internal
reflection sensor at theta(c) with the advantage of detecting a narrow dip rather
than an edge and enhanced figure of merit by increasing the number of periods in
the 1D-PC. Using the diverging beam approach on an optical bench, a two channel
sensor is demonstrated with a sensitivity of 120.9 deg/RIU and a detection limit
of 1.9*10(-5) RIU.
PMID- 26421539
TI - Photoswitchable and dye-doped bubble domain texture of cholesteric liquid
crystals.
AB - We demonstrate control of the transmittance of the naturally formed bubble domain
(BD) texture of cholesteric liquid crystals (CLC) with negative dielectric
anisotropy confined into a cell with homeotropic surface anchoring. By using a
photosensitive chiral dopant with variable helical twisting power under light
irradiation, control of packing density of bubbles, spatial patterning, and all
optical switching between bistable states with different optical densities is
achieved. By introducing dichroic dye into the CLC mixture, a bistable and
switchable by applied electric field guest-host system is obtained. The light
dimming properties of dye-doped BD CLC systems may lead to development of a wide
range of applications.
PMID- 26421540
TI - SU-8 nanoimprint fabrication of wire-grid polarizers using deep-UV interference
lithography.
AB - We describe a new fabrication method for making wire-grid polarizers for the
visible and near-IR based on deep-UV interference lithography, nanoimprint, and
glancing angle deposition. We fabricated aluminum wire grids with periods ranging
from 375 to 230 nm with heights from 145 to 110 nm, respectively. The measured
extinction ratio was as high as 220:1 at 1064 nm. The performance of the
polarizer is limited by the roughness and porosity of the Al film and the
underlying SU-8 structure. This method allows patterning of wire grids on any
substrate material, which makes this an attractive method for fabricating wire
grid micropolarizers in a timely and cost-effective manner.
PMID- 26421541
TI - Speed optimized linear-mode high-voltage CMOS avalanche photodiodes with high
responsivity.
AB - Two different speed optimized avalanche photodiodes (APDs) fabricated in a 0.35
MUm standard high-voltage (HV) complementary metal-oxide-semiconductor (CMOS)
process with a high unamplified responsivity (avalanche gain M=1) of 0.41 A/W at
670 nm are presented. These APDs differ regarding the effective doping of the
deep p well (90% and 75%), using lateral well modulation doping. Compared to the
3 dB bandwidth of the unmodulated APD with 100% doping (850 MHz), this
optimization leads to an improved bandwidth of 1.02 and 1.25 GHz for the 75% APD
and 90% APD, respectively, both at a gain of M=50.
PMID- 26421542
TI - Superluminal propagation through 500 m optical fiber via stimulated Brillouin
scattering.
AB - We have experimentally demonstrated superluminal propagation through a 500 m
optical fiber using stimulated Brillouin scattering (SBS), which is the longest
superluminal propagating distance reported so far, to the best of our knowledge.
Brillouin-induced loss resonance for fast light generation of pump signals is
achieved in a single frequency Brillouin lasing oscillator with a highly
nonlinear fiber as the SBS medium. The single frequency operation is realized by
embedding the saturable absorber fiber loop with an unpumped erbium-doped fiber.
Consequently, signals with a pulse width of 710 ns experience a maximum
advancement of 1330 ns. Furthermore, the effects of pulse width and the duty
cycle of pump signals are also investigated.
PMID- 26421543
TI - Electrically controllable extraordinary optical transmission in gold gratings on
vanadium dioxide.
AB - Highly tunable optical transmission through one-dimensional gold gratings
patterned on top of a film of the phase transition material, vanadium dioxide
(VO2), is demonstrated. Dense electrical integration is enabled by grating
features that also function as electrical contacts to the VO2. Extraordinary
optical transmission is observed in the VO2 insulator phase, and the optical
transmission is extinguished by up to about 6 dB in a 170 nm thick VO2 film.
Measurements of gratings with varying duty cycles demonstrate the dependence of
the optical transmission and tuning on the device geometry.
PMID- 26421544
TI - Phase measurement of soft x-ray multilayer mirrors.
AB - We propose a new model enabling the extraction of the phase of a multilayer
mirror from photocurrent measurements in the soft x rays. In this range, the
effects of the mean free path of the electrons inside the stack can no longer be
neglected, which prevents the phase reconstruction by conventional photocurrent
measurements. The new model takes into account this phenomenon and thus extends
up to the x rays the applicability range of the technique. This approach has been
validated through a numerical and experimental study of chromium/scandium
multilayers used near 360 eV. To our knowledge, this work constitutes the first
measurement of the phase of a multilayer mirror in the soft x-ray range.
PMID- 26421545
TI - Time-delay concealment and complexity enhancement of an external-cavity laser
through optical injection.
AB - The concealment of the time-delay signature (TDS) of chaotic external-cavity
lasers is necessary to ensure the security of optical chaos-based cryptosystems.
We show that this signature can be removed simply by optically injecting an
external-cavity laser with a large linewidth-enhancement factor into a second,
noninjection-locked, semiconductor laser. Concealment is ensured both in the
amplitude and in the phase of the optical field, satisfying a sought-after
property of optical chaos-based communications. Meanwhile, enhancement of the
dynamical complexity, characterized by permutation entropy, coincides with strong
TDS suppression over a wide range of parameters, the area for which depends
sensitively on the linewidth-enhancement factor.
PMID- 26421546
TI - Wide-field optical coherence microscopy of the mouse brain slice.
AB - The imaging capability of optical coherence microscopy (OCM) has great potential
to be used in neuroscience research because it is able to visualize anatomic
features of brain tissue without labeling or external contrast agents. However,
the field of view of OCM is still narrow, which dilutes the strength of OCM and
limits its application. In this study, we present fully automated wide-field OCM
for mosaic imaging of sliced mouse brains. A total of 308 segmented OCM images
were acquired, stitched, and reconstructed as an en-face brain image after
intensive imaging processing. The overall imaging area was 11.2*7.0 mm
(horizontal*vertical), and the corresponding pixel resolution was 1.2*1.2 MUm.
OCM images were compared to traditional histology stained with Nissl and Luxol
fast blue (LFB). In particular, the orientation of the fibers was analyzed and
quantified in wide-field OCM.
PMID- 26421548
TI - Widely tunable telecom MEMS-VCSEL for terahertz photomixing.
AB - We report frequency-tunable terahertz (THz) generation with a photomixer driven
by an ultra-broadband tunable micro-electro-mechanical system vertical-cavity
surface-emitting laser (MEMS-VCSEL) and a fixed-wavelength VCSEL, as well as a
tunable MEMS-VCSEL mixed with a distributed feedback (DFB) diode. A total
frequency span of 3.4 THz is covered in direct detection mode and 3.23 THz in the
homodyne mode. The tuning range is solely limited by the dynamic range of the
photomixers and the Schottky diode/photoconductor used in the experiment.
PMID- 26421547
TI - Cryogenic-temperature profiling of high-power superconducting lines using local
and distributed optical-fiber sensors.
AB - This contribution presents distributed and multipoint fiber-optic monitoring of
cryogenic temperatures along a superconducting power transmission line down to 30
K and over 20 m distance. Multipoint measurements were conducted using fiber
Bragg gratings sensors coated with two different functional overlays (epoxy and
poly methyl methacrylate (PMMA)) demonstrating cryogenic operation in the range
300-4.2 K. Distributed measurements exploited optical frequency-domain
reflectometry to analyze the Rayleigh scattering along two concatenated fibers
with different coatings (acrylate and polyimide). The integrated system has been
placed along the 20 m long cryostat of a superconducting power transmission line,
which is currently being tested at the European Organization for Nuclear Research
(CERN). Cool-down events from 300-30 K have been successfully measured in space
and time, confirming the viability of these approaches to the monitoring of
cryogenic temperatures along a superconducting transmission line.
PMID- 26421549
TI - Prediction of multiple resonance characteristics by an extended resistor-inductor
capacitor circuit model for plasmonic metamaterials absorbers in infrared.
AB - The resonance characteristics of plasmonic metamaterials absorbers (PMAs) are
strongly dependent on geometric parameters. A resistor-inductor-capacitor (RLC)
circuit model has been extended to predict the resonance wavelengths and the
bandwidths of multiple magnetic polaritons modes in PMAs. For a typical metallic
dielectric-metallic structure absorber working in the infrared region, the
developed model describes the correlation between the resonance characteristics
and the dimensional sizes. In particular, the RLC model is suitable for not only
the fundamental resonance mode, but also for the second- and third-order
resonance modes. The prediction of the resonance characteristics agrees fairly
well with those calculated by the finite-difference time-domain simulation and
the experimental results. The developed RLC model enables the facilitation of
designing multi-band PMAs for infrared radiation detectors and thermal emitters.
PMID- 26421550
TI - High-finesse sub-GHz-resolution spectrometer employing VIPA etalons of different
dispersion.
AB - We report a novel configuration of a two-stage virtually imaged phased array
spectrometer that enables high-throughput sub-GHz spectroscopy at a high finesse
(>750). Two etalons with different free spectral range and different dispersion
are arranged in an orthogonal direction and spread the spectrum across two
dimensions, with a greatly improved rejection ratio of white-light background
noise. A proof-of-concept application for Brillouin spectroscopy is demonstrated.
PMID- 26421551
TI - Complementary metal-oxide-semiconductor compatible 1060 nm photodetector with
ultrahigh gain under low bias.
AB - Falling on the tail of the absorption spectrum of silicon, 1060 nm Si detectors
often suffer from low responsivity unless an exceedingly thick absorption layer
is used, a design that requires high operation voltage and high purity epitaxial
or substrate material. We report an all-silicon 1060 nm detector with ultrahigh
gain to allow for low operation voltage (<4 V) and thin (200 nm) effective
absorption layer, using the recently discovered cycling excitation process. With
1% external quantum efficiency, a responsivity of 93 A/W was demonstrated in a
p/n junction device compatible with the complementary metal-oxide-semiconductor
process.
PMID- 26421552
TI - Unveiling the photonic spin Hall effect of freely propagating fan-shaped
cylindrical vector vortex beams.
AB - An intriguing photonic spin Hall effect (SHE) for a freely propagating fan-shaped
cylindrical vector (CV) vortex beam in a paraxial situation is theoretically and
experimentally studied. A developed model to describe this kind of photonic SHE
is proposed based on angular spectrum diffraction theory. With this model, the
close dependences of spin-dependent splitting on the azimuthal order of
polarization, the topological charge of the spiral phase, and the propagation
distance are accurately revealed. Furthermore, it is demonstrated that the
asymmetric spin-dependent splitting of a fan-shaped CV beam can be consciously
managed, even with a constant azimuthal order of polarization. Such a
controllable photonic SHE is experimentally verified by measuring the Stokes
parameters.
PMID- 26421553
TI - Fast subcellular optical coherence photoacoustic microscopy for pigment cell
imaging.
AB - We developed a fast ultrahigh resolution optical coherence photoacoustic
microscopy (FU-OCPAM) system by combining two complementary imaging modes of
optical coherence microscopy (OCM) and photoacoustic microscopy (PAM) for
cellular/subcellular imaging. The system used optical scanning to realize fast
imaging speed and provided ultrahigh resolution of 1.24 and 0.59 MUm for OCM and
PAM, respectively. We imaged the retinal pigment epithelium (RPE) to demonstrate
the subcellular imaging capability of the FU-OCPAM system. The OCM and PAM images
clearly showed the RPE cell morphology and reflected the complementary optical
properties of scattering and absorption. A quantitative analysis of the RPE cells
was made based on photoacoustic (PA) signals. The cell area mainly ranged from 80
to 300 MUm2, and had a linear relationship with the sum intensity of PA signals
which mainly reflected the melanin content of the cells. The morphology and the
PA signal could be used to identify qualitatively and quantitatively the aging
and healthy states of the RPE cells. The results show the potential applications
in studying the real-time cellular response to external stimulations and the
progress of aging and diseases at the cellular level with FU-OCPAM.
PMID- 26421554
TI - Distributed fiber surface plasmon resonance sensor based on the incident angle
adjusting method.
AB - We propose and demonstrate a distributed surface plasmon resonance (SPR) fiber
sensor based on a novel, simple, and effective incident angle adjusting method.
For normal fiber SPR sensors, it is hard to realize distributed sensing because
it is hard to produce two dynamic ranges (resonance wavebands) with a great
difference. The dynamic range depends on the incident angle, and therefore, we
propose an incident angle adjusting method that is implemented by grinding an
eccentric-core fiber to different angles, which helps to produce different SPR
wavebands with great difference, thus realizing distributed sensing. In our two
cascaded distributed configuration, with the refractive index range of 1.333
1.385, the fiber grind angles are 9 degrees and 17 degrees , the testing
wavelength ranges are 613-760 nm and 745-944 nm, and the average testing
sensitivities are 2826 nm/RIU and 4738 nm/RIU, respectively. Larger resonance
wavelengths are associated with larger testing sensitivities. This distributed
fiber sensor has important significance in the fields of multichannel liquid
refractive indices and temperature self-reference measurements.
PMID- 26421555
TI - Measurement of beam profiles by terahertz sensor card with cholesteric liquid
crystals.
AB - We demonstrate a sensor card with cholesteric liquid crystals (CLCs) for
terahertz (THz) waves generated from a nonlinear crystal pumped by a table-top
laser. A beam profile of the THz waves is successfully visualized as color change
by the sensor card without additional electronic devices, power supplies, and
connecting cables. Above the power density of 4.3 mW/cm2, the approximate beam
diameter of the THz waves is measured using the hue image that is digitalized
from the picture of the sensor card. The sensor card is low in cost, portable,
and suitable for various situations such as THz imaging and alignment of THz
systems.
PMID- 26421556
TI - Shaping of light beams by 3D direct laser writing on facets of nonlinear
crystals.
AB - We demonstrate experimentally spatial-mode conversions of light beams generated
in a quadratic nonlinear process by micron-scale structures placed on the facets
of nonlinear crystals. These structures were printed on the crystal facets using
a three-dimensional (3D) direct laser writing system. The functional structures
were designed to modify the phase of the beam at specific wavelengths, thereby
enabling conversion of a fundamental Gaussian laser beam into different high
order Hermite-Gaussian modes, Laguerre-Gaussian modes, and zeroth-order Bessel
beams of the second harmonic. This facet functionalization opens exciting new
opportunities for robust and compact beam shaping in a nonlinear interaction
without compromising the conversion efficiency.
PMID- 26421557
TI - Compressive correlation imaging with random illumination.
AB - Achieving high rates and high resolution in noisy conditions is a main desiderate
for computational imaging. Here, we demonstrate both numerically and
experimentally that binary illumination based on spatially random distributions
provides superior imaging capabilities at high compression ratios while operating
in noisy environments. The proposed method permits decreasing the time for image
formation without adding complexity to the imaging system or compromising the
resolution.
PMID- 26421558
TI - Mechanoluminescence of ZnS:Mn phosphors and its correlation to impact energy and
contact geometry.
AB - The influence of the impulsive mechanical energy and the contact geometrical
parameters on stress-induced light emission of ZnS-based phosphors dispersed in
polymeric matrix is investigated using modified impact test equipment. At a low
to moderate energy region, luminescent pulses consist of two distinguishable
peaks that can be assigned to a loading and unloading sequence, respectively.
Transient characteristics are found to be independent of the external excitation.
An increment of peak emission intensity with higher impact energy and smaller tip
diameter indicates a significant relationship of mechanoluminescence to the
geometry of contact. Intense emission deviating from the linearity and an absence
of the secondary peak are suggested to be the consequence of fractoluminescence.
PMID- 26421559
TI - Stabilized phase detection of heterodyne sum frequency generation for interfacial
studies.
AB - We present a collinear-geometry heterodyne sum frequency generation (HD-SFG)
method for interfacial studies. The HD detection is based on a collinear SFG
configuration, in which picosecond visible and femtosecond IR beams are used to
first produce a strong local oscillator and then to generate weak SFG signals
from an interface. A time-delay compensator, consisting of an MgF2 window, is
placed before the sample to introduce the time delay between the local oscillator
and the interfacial SFG signals for spectral interferometry. Our HD-SFG method
exhibits advantages of long-time phase stability. It is not sensitive to sample
heights, does not require reflection correction, and is easy to implement.
PMID- 26421560
TI - Robust postfabrication trimming of ultracompact resonators on silicon on
insulator with relaxed requirements on resolution and alignment.
AB - One of the main drawbacks of the high-index-contrast silicon-on-insulator
platform in integrated photonics is the high sensitivity of the resonance
wavelength of resonators to dimensional variations caused by fabrication
imperfection. In this work, we experimentally demonstrate an accurate
postfabrication trimming technique for compensating the fabrication-induced
variations in the resonance properties of nanophotonic devices. Using this
technique, we reduce the variation of the resonance wavelength of 4 MUm diameter
microdonut resonators by more than 1 order of magnitude to about 25 pm, which is
adequate for most interconnect, optical signal processing, and sensing
applications. In addition, our proposed technique has improved misalignment
toleration and throughput compared to previous reports.
PMID- 26421561
TI - Proposed high-speed micron-scale spatial light valve based on a silicon-graphene
hybrid structure.
AB - We propose a new ultracompact CMOS-compatible variable-transmission spatial light
valve based on a silicon-graphene hybrid structure. Normally incident ~1560 nm
light can be coupled to a silicon-graphene-based 1D photonic crystal cavity
through a perturbation-based diffractive coupling scheme. The lightwave
modulation is achieved by tuning the Fermi level of the graphene, which can
change both the loss and the resonant wavelength of the cavity. Based on finite
difference time-domain simulation, the modulation depth is larger than 10 dB with
driving voltage of about 4.8 V(pp) while the modulation speed is estimated to be
higher than 45 GHz.
PMID- 26421562
TI - Noncollinear third-harmonic generation with large angular acceptance by
noncritical phase matching in KDP crystal.
AB - The scheme of prefocusing to focus sum frequency generation (SFG) without a lens
is proposed and experimentally verified in this study. Noncollinear type-I
noncritical phase-matching SFG to generate a third-harmonic wave with large
angular acceptance is presented. The principle of broad angular acceptance and
the advantages of this PM configuration are also described in detail. External
angular bandwidth of 7.33 degrees for noncollinear SFG was measured in a 2 mm
long KH2PO4 (KDP) crystal, which is in reasonably good agreement with the
theoretical calculation. The mechanism of broadband SFG and the prefocusing
scheme make it possible for the realization of convergent third-harmonic
generation without involving a lens, which provides a promising way to avoid
damage to optical components during the focusing of high-energy UV light in high
power laser facilities.
PMID- 26421563
TI - Dispersion of coupled mode-gap cavities.
AB - The dispersion of a coupled resonator optical waveguide made of photonic crystal
mode-gap cavities is pronouncedly asymmetric. This asymmetry cannot be explained
by the standard tight binding model. We show that the fundamental cause of the
asymmetric dispersion is the inherent dispersive cavity mode profile; i.e., the
mode wave function depends on the driving frequency, not the eigenfrequency. This
occurs because the photonic crystal cavity resonances do not form a complete set.
We formulate a dispersive mode coupling model that accurately describes the
asymmetric dispersion without introducing any new free parameters.
PMID- 26421564
TI - Self temperature regulation of photothermal therapy by laser-shared photoacoustic
feedback.
AB - This article describes a laser-shared photothermal system that achieves tight
temperature regulation by frequency-domain photoacoustic (FD-PA) feedback. To
this end, a continuous-wave laser system was designed with arbitrarily
modulatable laser intensity. And, by fast alternating in the time domain between
a constant laser intensity for photothermal heating and a modulated laser
intensity for FD-PA temperature measurement, photothermal temperature variations
are captured by FD-PA in real time. A proportional-integral-derivative (PID)
controller monitors the feedback from FD-PA measurements and controls
photothermal heating dose accordingly, thus stabilizing the temperature at preset
values. The proposed system is demonstrated to achieve ultrafast temperature
measurement at a 4 kHz rate, and with proper averaging, the measurement and
regulation accuracy are 0.75 deg and 0.9 deg respectively.
PMID- 26421565
TI - Two-frequency pulsed YLiF4:Nd lasing out of the principal axes and THz
generation.
AB - Thanks to a propagation direction at 50.3 degrees from the c axis in a LiYF4:Nd
crystal, we have equalized the emission cross-sections at 1047 and 1053 nm,
respectively, for extraordinary and ordinary waves. The double refraction is used
to balance the "o" and "e" pumping. Actively Q-switching the laser cavity leads
to simultaneous pulses with duration less than 10 ns. Frequency conversion to THz
radiation was performed through difference frequency mixing in two nonlinear
crystals: GaSe and OH1. In the first case, we obtained 132 nW and in the second
case we obtained 51 nW THz power at 6.67 kHz repetition rate.
PMID- 26421566
TI - Coherence enhancement of a chirped DFB laser for frequency-modulated continuous
wave reflectometry using a composite feedback loop.
AB - We demonstrate efficient coherence enhancement of a chirped distributed feedback
(DFB) laser for frequency-modulated continuous-wave (FMCW) reflectometry. Both
sweep nonlinearity and broadband stochastic frequency noises during the laser
chirp are efficiently suppressed by a composite feedback loop. The residual
frequency error relative to a perfect linear chirp is shown to be about 89 kHz
for a laser chirp of 50 GHz in 100 ms, compared with 44 MHz with the loop open.
The broadband frequency noise suppression of the frequency-swept laser greatly
improves its coherence, leading to a higher signal-to-noise ratio and a
significantly extended measurement range in FMCW reflectometry ranging. We
demonstrate a 2 mm transform-limited spatial resolution at a range window of 50 m
and a 17.5 cm spatial resolution at an extended measurement range of 750 m, which
is about 15 times the intrinsic laser round-trip coherence length.
PMID- 26421567
TI - Twisted Schell-model beams with axial symmetry.
AB - The problem of when a twist can be impressed on a partially coherent beam is
solved for Schell-model fields endowed with axial symmetry. A modal analysis can
be performed for any such beam, thus permitting evaluation of whether it will
withstand the twisting process. Beyond exemplifying some twistable beams, it is
shown that, for certain correlation functions, the beam cannot be twisted, no
matter how the numerical parameters are chosen.
PMID- 26421568
TI - Generation of hyper-parametric oscillations in silica microbubbles.
AB - Cavity resonant enhanced stimulated Raman scattering (SRS), four-wave mixing, and
broadband hyper-parametric oscillation in silica microbubble whispering gallery
mode resonators (WGMR) in forward and backward directions are reported in this
Letter. We show that microbubbles can operate not only in a highly ideal two
photon emission regime, but also generate combs, both natively and multi-mode
spaced. The nonlinear process is phase matched because of the interaction of
different mode families of the resonator.
PMID- 26421569
TI - Tuning nanosecond transient absorption in a-Ge25As10Se65 thin films via
background illumination.
AB - In this Letter, we report for the first time, to the best of our knowledge,
continuous-wave laser background illumination (BGI) as a simple and yet useful
tool to tune nanosecond transient absorption (TA) in a-Ge25As10Se65 thin films.
In our experiments, we observed remarkable blueshift in TA as a function of the
BGI intensity. Strikingly, relaxations of TA in background-illuminated samples
are much faster than the as-prepared samples. This observation provides new
insights into the bond-breaking mechanism. Further, decay time constants of TA
are wavelength dependent, which signifies that excited carriers have a longer
lifetime in deep traps than in shallow traps.
PMID- 26421570
TI - Polarization properties of the Airy beam.
AB - Polarization of paraxial Airy beam solutions of Maxwell's equations and its
evolution with propagation have been studied. We experimentally demonstrate the
existence of the cross-polarization component of the Airy beam, typical of
nonplanar phase fronts, and study its evolution with propagation.
PMID- 26421571
TI - Dual-period tunable phase grating using polymer stabilized blue phase liquid
crystal.
AB - Dual-period tunable phase grating using polymer stabilized blue phase liquid
crystal is demonstrated by controlling its driving scheme. High efficiencies of
35.3% for the small-period phase grating and 28.7% for the large-period phase
grating have been achieved because of the rectangular-like phase profile which
shows good agreement with the simulation results. The diffraction angle can be
alternatively tuned, as well as the diffraction efficiency. Moreover, this device
also possesses polarization independency and fast response with a rise time of
826 MUs and a decay time of 1.143 ms which shows great potential for diffractive
optics.
PMID- 26421572
TI - Coupling of plasmon and photon modes in a graphene-based multilayer structure.
AB - We propose a graphene-based plasmonic heterostructure in which a new class of
plasmon polariton modes can be realized via fundamental coupling of conventional
graphene plasmons (GPs) and spoof surface plasmons or radiation modes. We name
these electromagnetic modes coupled graphene plasmon polaritons (CGPPs). It is
found that the properties of the CGPPs can be tuned by the geometry of the
heterostructure, the material used to fill the holes, and the electron density in
graphene. Most interestingly, we show that it is possible to achieve CGPPs with
about 10 times enhancement of wave localization or about 300 times enhancement of
propagation length, compared to usual GPs through varying device parameters.
These features can be applied to tunable terahertz and infrared plasmonic
devices.
PMID- 26421573
TI - Four-wave-mixing in the loss low submicrometer Ta2O5 channel waveguide.
AB - A degenerate four-wave-mixing (FWM) operation in the Ta2O5 submicrometer channel
waveguide has been successfully demonstrated. The propagation loss of 1.5 dB/cm
and total insertion loss of 5.1 dB are realized in a 12.6 mm long waveguide with
inverse taper structure. The wavelength and quadratic pumping power-dependent
measurements on optical transmission confirm FWM performance and characterize the
nonlinearity of waveguide. The conversion efficiency of -50 dB at coupled pump
power of 40 mW is observed, suggesting that the nonlinear refractive index of
Ta2O5 waveguide at 1550 nm is estimated to be 1*10(-14) cm2/W. Our primary
results indicate that the Ta2O5 submicrometer channel waveguide has great
potential in developing nonlinear waveguide applications.
PMID- 26421574
TI - Near-field radiative transfer between magneto-dielectric uniaxial anisotropic
media.
AB - We investigate the near-field radiative heat transfer between two semi-infinite
magneto-dielectric uniaxial anisotropic media (MDUAM). SiC nanowires embedded in
metamaterials are used to implement electric and magnetic anisotropy, which leads
to the hyperbolic dispersion relation for both TE and TM waves. The results show
that the TM and TE waves can support both hyperbolic modes and surface modes and
that there exist additional modes contributing to the heat transfer for TE waves.
Moreover, the MDUAM exhibit super-Planckian thermal emission at ultra-broad
bandwidths. This work paves the way for applying the near-field radiative heat
transfer in the area of thermal management and energy harvesting.
PMID- 26421575
TI - Spectral modification of whispering-gallery-mode resonances in spheroidal
resonators due to interaction with ultra-small particles.
AB - The recently developed general ab initio theory of nanoparticle-induced
modifications of the spectrum of whispering gallery modes of optical spheroidal
resonators is applied to the case in which distinct particle-induced resonances
overlap and cannot be resolved. This situation occurs in the case of resonances
with low Q-factors and/or ultra-small particles. The position of the single
resonance observed in these situations depends on the strengths and widths of the
overlapping resonances. We determine this position by considering the spectral
characteristics of the total power scattered by the resonator. The obtained
theoretical results are compared against the available experimental data and
heuristic theories.
PMID- 26421576
TI - Continuous wave terahertz radiation from antennas fabricated on C12-irradiated
semi-insulating GaAs.
AB - We demonstrate continuous wave (CW) terahertz generation from antennas fabricated
on C12-irradiated semi-insulating (SI) GaAs substrates. The dark current drawn by
the antennas fabricated on irradiated substrates is ~3 to 4 orders of magnitude
lower compared to antennas fabricated on un-irradiated substrates, while the
photocurrents decrease by only ~1.5 orders of magnitude. This can be attributed
to the strong reduction of the carrier lifetime that is 2.5 orders of magnitude,
with values around tau(rec)=0.2 ps. Reduced thermal heating allows for higher
bias voltages to the irradiated antenna devices resulting in higher CW terahertz
power, just slightly lower than that of low-temperature grown GaAs (LT GaAs)at
similar excitation conditions.
PMID- 26421577
TI - Fluorescence intensity ratio method for temperature sensing.
AB - A thermometry method based on the ratio between the valley intensity formed by
fluorescence peak overlap and the peak fluorescence intensity has been developed.
Excited by a 405 nm laser, the valley to peak ratio (VPR) of the emissions
originating from 5D0 to 7F2 Stark sublevels in Eu3+-doped CaWO4 shows a monotonic
change with temperature. Spectrum analysis indicates that this monotonic increase
is caused by the homogeneous broadening of the spectral lines as the temperature
increases. The relative sensitivity S(r) is in the magnitude of 10(-4) K(-1) in
the experimental temperature range of 303-573 K.
PMID- 26421578
TI - Angular dependence of filament-induced plasma emission from a GaAs surface.
AB - Quantitative measurements of the angular distribution of the plasma line emission
from a gallium arsenide (GaAs) target irradiated by a single laser-air filament
are reported. These enable reliable estimates of the stand-off ranges possible
with single-filament-induced laser-induced breakdown spectroscopy materials
detection.
PMID- 26421579
TI - Linear response, multi-order grating interferometry using a reversal shearing
imaging system.
AB - Linear response, multi-order grating interferometry is proposed to measure
grating displacement. The system, a combination of a reversal shearing
interferometer and an imaging system, enables calculating multi-order, integrated
intensity signals with a linear waveform response. A theoretical multi-order
model for the linear response signal analysis is presented with a Fourier series
expansion. The results of the experiment, which prove the validity of the
theoretical model, indicate a linear response to displacement with a linearity of
98.7% and a resolution of 10 nm. We conclude that the proposed method enables the
development of a new class of potent linear response grating interferometry for
displacement metrology.
PMID- 26421580
TI - Error probability performance of a short-reach multicore fiber optical
interconnect transmission system.
AB - A standalone module for rectangular array multicore fiber (MCF)-based optical
interconnect (OI) is realized that includes inherent intercore crosstalk and
provides space division multiplexed coupling/decoupling of optical power. The
module is integrated in a short-reach communication system to provide bit error
probability (BEP). Next, a closed-form equation for BEP applicable to MCF OI with
intercore crosstalk is derived. For characteristic parameters of the module,
results obtained by two approaches agree within 1% for 40 Gbps per channel and
predict an error-free transmission of aggregated data rate of 2.5 Tbps through
the MCF OI under consideration.
PMID- 26421581
TI - Real-time multiplexed digital cavity-enhanced spectroscopy.
AB - Cavity-enhanced spectroscopy is a sensitive optical absorption technique but one
where the practical applications have been limited to studying small wavelength
ranges. This Letter shows that wideband operation can be achieved by combining
techniques usually reserved for the communications community with that of cavity
enhanced spectroscopy, producing a multiplexed real-time cavity-enhanced
spectrometer. We use multiple collinear laser sources operating asynchronously
and simultaneously while being detected on a single photodetector. This is
synonymous with radio frequency (RF) cellular systems in which signals are
detected on a single antenna but decoded uniquely. Here, we demonstrate results
with spectra of methyl salicylate and show parts-per-billion per root hertz
sensitivity measured in real-time.
PMID- 26421582
TI - 10 m/25 Gbps LiFi transmission system based on a two-stage injection-locked 680
nm VCSEL transmitter.
AB - A 10 m/25 Gbps light-based WiFi (LiFi) transmission system based on a two-stage
injection-locked 680 nm vertical-cavity surface-emitting laser (VCSEL)
transmitter is proposed. A LiFi transmission system with a data rate of 25 Gbps
is experimentally demonstrated over a 10 m free-space link. To the best of our
knowledge, it is the first time a two-stage injection-locked 680 nm VCSEL
transmitter in a 10 m/25 Gbps LiFi transmission system has been employed.
Impressive bit error rate performance and a clear eye diagram are achieved in the
proposed systems. Such a 10 m/25 Gbps LiFi transmission system provides the
advantage of a communication link for higher data rates that could accelerate the
deployment of visible laser light communication.
PMID- 26421583
TI - Polarization sensitive phase-shifting Mirau interferometry using a liquid crystal
variable retarder.
AB - We present all-optical motionless arrangement for polarization sensitive phase
shifting (P-S) interferometry, where the phase shifts are accurately implemented
by a liquid crystal variable retarder (LCVR). The LCVR is used as a polarization
selective device capable of introducing a computer-controlled phase retardance
between signal and reference waves with orthogonal linear polarizations. The
proposed optical P-S is deployed in a polarization adapted common-path Mirau
interferometer. Application of the method to a setup using the Michelson
interference objective or Linnik interference module is also outlined. The
accuracy of the quantitative phase reconstruction is examined theoretically, and
a possibility to reduce the optical path difference error below 1/200 wavelength
is demonstrated experimentally. Benefits and application potential of the
polarization P-S interferometry supported by versatile liquid crystal devices are
also discussed.
PMID- 26421584
TI - Conscientious Objection or Dishonorable Disobedience?
PMID- 26421585
TI - Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft
tissue sarcoma patients.
AB - BACKGROUND: Alkylating agents, such as cyclophosphamide and ifosfamide, play a
major role in the improved survival of children and young adults with bone and
soft tissue sarcoma. However, there is still controversy as to their comparative
anti-tumour efficacy and possible adverse effects. This is the second update of
the first systematic review evaluating the state of evidence on the effectiveness
of cyclophosphamide as compared to ifosfamide for paediatric and young adult
patients with sarcoma. OBJECTIVES: The primary obective was to compare the
effectiveness, that is response rate, event-free survival and overall survival,
of cyclophosphamide with that of ifosfamide for paediatric and young adult
patients with sarcoma. Secondary objectives were to determine effects of these
agents on toxicities (including late effects) and quality of life. SEARCH
METHODS: We searched CENTRAL (The Cochrane Library 2015, issue 2), MEDLINE/PubMed
(from 1966 to March 2015) and EMBASE/Ovid (from 1980 to March 2015) with
prespecified terms. In addition, we searched reference lists of relevant
articles, conference proceedings and ongoing trial databases (www.controlled
trials.com; searched June 2015). SELECTION CRITERIA: Randomised controlled trials
(RCTs) or controlled clinical trials (CCTs) comparing cyclophosphamide and
ifosfamide for the treatment of different types of sarcoma in paediatric and
young adult patients (aged less than 30 years at diagnosis). Chemotherapy other
than either cyclophosphamide or ifosfamide should have been the same in both
treatment groups. DATA COLLECTION AND ANALYSIS: Two authors independently
performed the study selection. MAIN RESULTS: No studies meeting the inclusion
criteria of the review were identified. AUTHORS' CONCLUSIONS: No RCTs or CCTs
comparing the effectiveness of cyclophosphamide and ifosfamide in the treatment
of bone and soft tissue sarcoma in children and young adults were identified.
Therefore no definitive conclusions can be made about the effects of
cyclophosphamide and ifosfamide in these patients. Based on the currently
available evidence, we are not able to give recommendations for clinical
practice. More high-quality research is needed.
PMID- 26421586
TI - Outcome of patients with clinically node-positive bladder cancer undergoing
consolidative surgery after preoperative chemotherapy: The M.D. Anderson Cancer
Center Experience.
AB - PURPOSE: Patients with urothelial cancer with nodal metastasis have a poor
prognosis, with many deemed incurable. We report outcomes of a prospective
clinical protocol of patients with clinically node-positive disease treated via a
multimodality treatment approach. PATIENTS AND METHODS: A total of 55 patients
with bladder urothelial carcinoma with concurrent node-positive disease including
pelvic nodal and retroperitoneal lymph node (RPLN) involvement underwent
preoperative chemotherapy followed by consolidative surgery between 1995 and
2010. Associations between clinicopathologic factors and outcomes were analyzed
using log-rank test and Cox regression analysis. RESULTS: Median cancer-specific
survival (CSS) was 26 months (95% CI: 12.9-not applicable) for all patients. A
total of 30 (55%) patients had pN0 category disease at the time of surgical
extirpation. Despite radiologic complete response after chemotherapy, 6 of 21
patients (29%) had pN+category disease. The 5-year CSS rate was 66% for pN0
category disease vs. 12% for pN+category disease (P<0.001). Radiologic complete
response to chemotherapy was associated with a 5-year CSS rate of 60% vs. 33% for
a partial response (P = 0.038). Although no recurrences occurred within the
lymphadenectomy template, 2 (14%) patients with cM1 RPLN disease who did not
undergo RPLN dissection had recurrences in the RPLN basin and died within 6
months. CONCLUSION: Multimodality treatment approach with upfront chemotherapy
followed by surgery can result in a 66% 5-year CSS rate for patients rendered as
having pN0 category disease despite initially presenting with node-positive
disease. However, as those with residual disease do so poorly, further efforts in
refining selection of patients for surgical consolidation are needed.
PMID- 26421587
TI - Targeted p21(WAF1/CIP1) activation by miR-1236 inhibits cell proliferation and
correlates with favorable survival in renal cell carcinoma.
AB - BACKGROUND: microRNA's function to silence gene expression by targeting 3'UTR
regions has been widely studied. And microRNAs, similar to small double-stranded
RNAs, have also been implicated to gene activation triggered by promoter
targeted, which is known as RNA activation (RNAa). p21(WAF1/CIP1) (p21), as a key
negative regulator of cell proliferation, is frequently down-regulated in various
cancers, making it an ideal target for RNAa-based activation to restore its tumor
suppressor function in renal cell carcinoma (RCC). METHODS: Real-time polymerase
chain reaction was used to identify the expression of miR-1236 and p21 in RCC
cell lines and clinical specimens. Protein expression and signaling pathway
modulation were validated through Western blot analysis, whereas p21, direct
target of miR-1236, was validated by using chromatin immunoprecipitation assay.
The Kaplan-Meier method and the log-rank test were used to calculate overall
survival. The CellTiter 96((r)) AQueous One Solution Cell Proliferation Assay,
colony formation assay, and 5-ethynyl-2'-deoxyuridine assays were used to
evaluate the effect of miR-1236 on RCC cell proliferation. RESULTS: In this
study, we found that miR-1236 and p21 were both significantly down-regulated in
RCC tissues and cell lines. Combined low expression of both miR-1236 and p21
emerged as an independent prognostic factor for poor clinical survival in 45
patients with RCC. Chromatin immunoprecipitation assay in the human RCC cell
lines 786-O and ACHN showed that miR-1236 directly targeted the p21 promoter and
that its activation may provide a plausible link between the positive correlation
of miR-1236 and p21 in RCC specimens. Functional experiments showed that
increased miR-1236 expression inhibited cell proliferation, and decreased CDK4/6
and cyclin D1 expression. Furthermore, knockdown of p21 using small interfering
RNA reversed the antiproliferation function of miR-1236, whereas silencing the
p21 expression attenuated the function of miR-1236 in RCC cells. CONCLUSION: Our
findings provide insight into the specific RNAa of miR-1236-targeted p21 promoter
activation in suppressing RCC cell proliferation. Considering the poor prognostic
outcomes associated with reduced miR-1236 and p21 expression, our data imply that
these factors likely play important antitumor effects in RCC progression.
PMID- 26421588
TI - Variation in Patient Characteristics and Outcomes Between Early and Delayed
Surgery in Poor-Grade Aneurysmal Subarachnoid Hemorrhage.
AB - BACKGROUND: There is no consensus regarding the optimal timing for surgery for
poor-grade aneurysmal subarachnoid hemorrhage. OBJECTIVE: To retrospectively
evaluate variation in patient characteristics and outcomes between early and
delayed surgery groups. METHODS: Poor-grade aneurysmal subarachnoid hemorrhage
was defined as a World Federation of Neurosurgical Societies grade of IV or V
after resuscitation. Early surgery was defined as surgery performed within 72
hours of ictus, and delayed surgery was defined as surgery after 72 hours.
Outcomes were assessed by modified Rankin score. The mean time of follow-up was
12.5 +/- 3.4 months. RESULTS: Of the 118 patients included in the study, 80 (68%)
underwent early surgery and 38 (32%) underwent delayed surgery. Patients with
brain herniation (P < .001) and a lower Fisher grade (P = .02) more often
underwent early surgery. Patients in the early group more often underwent
decompressive craniectomy (P < .001). Postoperative complications and length of
hospital stay did not differ, and outcomes were similar between the 2 groups.
Forty (34%) patients had an excellent outcome (modified Rankin score 0-1).
Multivariate analysis showed a slight trend toward an excellent outcome in the
early surgery group. Younger age, World Federation of Neurosurgical Societies
grade IV after resuscitation, and middle cerebral artery aneurysms were
independent predictors of an excellent outcome. CONCLUSION: Although patients
with brain herniation and a lower Fisher grade were more likely to undergo early
surgery, there was a slight trend toward an excellent outcome in the early
surgery group. Patients with a younger age, World Federation of Neurosurgical
Societies grade IV after resuscitation, and middle cerebral artery aneurysms were
more likely to experience an excellent outcome.
PMID- 26421589
TI - Detection of Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage
Using Motor Evoked Potentials.
AB - BACKGROUND: Early detection of vasospasm (VS) following aneurysmal subarachnoid
hemorrhage (aSAH) is vital to trigger therapy and to prevent infarction and
subsequent permanent neurological deficit. Although motor evoked potentials
(MEPs) are a well-established method for intraoperative detection of cerebral VS
and cerebral ischemia during aneurysm surgery, there are no studies investigating
the diagnostic value of MEPs for detecting delayed VS following aSAH in an
intensive care unit. OBJECTIVE: A prospective study was conceived to assess the
diagnostic accuracy of MEPs in comparison with digital subtraction angiography.
METHODS: MEP threshold changes were determined in patients both with and without
angiographic VS following high-grade aSAHs. Sensitivity, specificity, and the
positive and negative predictive values of significant MEP threshold increases,
which indicate angiographic VS, were calculated. RESULTS: In all patients
experiencing VS of the arteries supplying cerebral motor areas, a minimal MEP
threshold increase of 50 mA (mean 66.25 mA) was observed, whereas a maximum MEP
threshold increase of 30 mA was observed in patients without VS. Therefore, an
increase from a baseline of >=50 mA was considered significant and resulted in a
sensitivity of 0.83, a specificity of 0.92, a positive predictive value of 0.83,
and a negative predictive value of 0.92. CONCLUSION: VS following aSAH can be
detected accurately by using MEPs. MEPs are a feasible bedside tool for online VS
detection in an intensive care unit and, therefore, may complement existing
diagnostic tools.
PMID- 26421590
TI - Predictors of Poor Quality of Life 1 Year After Subarachnoid Hemorrhage.
AB - BACKGROUND: Risk factors for poor quality of life (QOL) after subarachnoid
hemorrhage (SAH) remain poorly described. OBJECTIVE: To identify the frequency
and predictors of poor QOL 1 year after SAH. METHODS: We studied 1-year QOL in a
prospectively collected cohort of 1181 consecutively admitted SAH survivors
between July 1996 and May 2013. Patient clinical, radiographic, surgical, and
acute clinical course information was recorded. Reduced QOL (overall, physical,
and psychosocial) at 1 year was assessed with the Sickness Impact Profile and
defined as 2 SD below population-based normative Sickness Impact Profile values.
Logistic regression leveraging multiple imputation to handle missing data was
used to evaluate reduced QOL. RESULTS: Poor overall QOL was observed in 35% of
patients. Multivariable analysis revealed that nonwhite ethnicity, high school
education or less, history of depression, poor clinical grade (Hunt-Hess Grade
>=3), and delayed infarction were predictors of poor overall and psychosocial
QOL. Poor physical QOL was additionally associated with older age, hydrocephalus,
pneumonia, and sepsis. At 1 year, patients with poor QOL had increased difficulty
concentrating, cognitive dysfunction, depression, and reduced activities of daily
living. More than 91% of patients with poor QOL failed to fully return to work.
These patients frequently received physical rehabilitation, but few received
cognitive rehabilitation or emotional-behavioral support. CONCLUSION: Reduced QOL
affects as many as one-third of SAH survivors 1 year after SAH. Delayed
infarction is the most important in-hospital modifiable factor that affects QOL.
Increased attention to cognitive and emotional difficulties after hospital
discharge may help patients achieve greater QOL.
PMID- 26421592
TI - Long-Term Results of Stereotactic Radiosurgery for Skull Base Meningiomas.
AB - BACKGROUND: Gamma knife radiosurgery (GKRS) is well established in the management
of inaccessible, recurrent, or residual benign skull base meningiomas. Most
series report clinical outcome parameters and complications in the short
intermediate period after radiosurgery. Reports of long-term tumor control and
neurological status are still lacking. OBJECTIVE: To report the presentation,
treatment, and long-term outcome of skull base meningiomas after GKRS. METHODS:
From a prospectively collected institutional review board-approved database, we
selected patients with a World Health Organization grade I skull base meningioma
treated with a single-session GKRS and a minimum of 60 months follow-up. One
hundred thirty-five patients, 54.1% males (n = 73), form the cohort. Median age
was 54 years (19-80). Median tumor volume was 4.7 cm (0.5-23). Median margin dose
was 15 Gy (7.5-36). Median follow-up was 102.5 months (60.1-235.4). Patient and
tumor characteristics were assessed to determine the predictors of neurological
function and tumor progression. RESULTS: At last follow-up, tumor volume control
was achieved in 88.1% (n = 119). Post-GKRS clinical improvement or stability was
reported in 61.5%. The 5-, 10-, and 15-year actuarial progression-free survival
rates were 100%, 95.4%, and 68.8%, respectively. Favorable outcome (both tumor
control and clinical preservation/improvement) was attained in 60.8% (n = 79).
Pre-GKRS performance status (Karnofsky Performance Scale) was shown to influence
tumor progression (P = .001) and post-GKRS clinical improvement/preservation (P =
.003). CONCLUSION: GKRS offers a highly durable rate of tumor control for World
Health Organization grade I skull base meningiomas, with an acceptably low
incidence of neurological deficits. The Karnofsky Performance Scale at the time
of radiosurgery serves as a reliable long-term predictor of overall outcome.
ABBREVIATIONS: ARE, adverse radiation effectGKRS, Gamma knife radiosurgeryKPS,
Karnofsky Performance ScaleWHO, World Health Organization.
PMID- 26421593
TI - Lung cancer treatment is influenced by income, education, age and place of
residence in a country with universal health coverage.
AB - Selection of lung cancer treatment should be based on tumour characteristics,
physiological reserves and preferences of the patient. Our aims were to identify
and quantify other factors associated with treatment received. Lung cancer
patient data from 2002 to 2011 were obtained from the national population-based
Cancer Registry of Norway, Statistics Norway and the Norwegian Patient Register.
Multivariable logistic regression examined whether year of diagnosis, age, sex,
education, income, health trust, smoking status, extent of disease, histology and
comorbidities were associated with choice of treatment; surgery or radical or
palliative radiotherapy, within 1 year of diagnosis. Among the 24,324 lung cancer
patients identified, the resection rate remained constant while the proportion of
radical radiotherapy administered increased from 8.6 to 14.1%. Older patients,
those with lower household incomes and certain health trusts were less likely to
receive any treatment. Lower education and the male gender were identified as
negative predictors for receiving surgery. Smoking history was positively
associated with both radical and palliative radiotherapy, while comorbidity and
symptoms were independently associated with receiving surgery and palliative
radiotherapy. Although Norway is a highly egalitarian country with a free,
universal healthcare system, this study indicates that surgery and radical and
palliative radiotherapy were under-used among the elderly, those with a lower
socioeconomic status and those living in certain health trusts.
PMID- 26421594
TI - Correlation of minimal extrathyroidal extension with pathologic features of lymph
node metastasis in patients with papillary thyroid carcinoma.
AB - BACKGROUND: The impact of minimal extrathyroidal extension (mETE) to the
prognosis of patients with papillary thyroid carcinoma (PTC) is controversial. In
this study, we investigated whether mETE is related to the aggressive biology of
metastatic lymph node (LN) in patients with PTC. METHODS: A retrospective review
of 369 patients who had biopsy-confirmed cervical LN metastasis after initial
surgery for PTC was conducted. The correlations of mETE with the specific
features of metastatic LNs such as the LN size, number, LN ratio, and presence of
extranodal extension (ENE) were statistically analyzed. RESULTS: Size of the
primary tumor (>=1 cm) had independent correlations to mETE (HR = 5.750). While
mETE was related to number of metastatic LNs (>=5), LN ratio (>=0.31) and ENE in
univariate analysis, only ENE (HR = 2.322) was independently correlated to mETE
in our series. Along with mETE, size of primary tumor (>=1 cm) had significant
impact on ENE (HR = 2.107). CONCLUSION: Minimal ETE particularly those with
larger primary tumor (>=1 cm) may be still considered as a significant factor
regarding the management of cervical LNs in patients with PTC.
PMID- 26421595
TI - Trauma-induced schwannoma of the recurrent laryngeal nerve after thyroidectomy.
AB - Laryngeal schwannomas are rare, benign tumors, most often arising from the
superior laryngeal nerve. We describe a case of a 68-year-old female with a
laryngeal schwannoma of the recurrent laryngeal nerve after traumatic injury. We
postulate that trauma to the recurrent laryngeal nerve during thyroidectomy or
thyroplasty incited growth of a nerve sheath tumor. This is the first reported
case of a trauma-induced schwannoma of the recurrent laryngeal nerve and second
case of a recurrent laryngeal nerve schwannoma. Although rare, this case
demonstrates that these tumors should be considered during workup of vocal cord
paresis after surgery or failed thyroplasty. Laryngoscope, 126:1408-1410, 2016.
PMID- 26421596
TI - Protective immunity against acute toxoplasmosis in BALB/c mice induced by a DNA
vaccine encoding Toxoplasma gondii 10 kDa excretory-secretory antigen (TgESA10).
AB - Toxoplasma gondii 10 kDa excretory-secretory antigen (TgESA10) is involved in the
early stages of host invasion. The aim of this study was to evaluate the immune
protective efficacy of a DNA vaccine encoding TgESA10 gene against acute T.
gondii infection in mice. The gene sequence encoding TgESA10 was inserted into
the eukaryotic expression vector pVAX I, and the efficacy of intramuscular
vaccination of BALB/c mice with pVAX-ESA10 was analyzed. Mice immunized with pVAX
ESA10 elicited high titers of total IgG, IgG1, IgG2a, IgA and IgM antibodies,
while IgE showed no changes. Analysis of cytokine profiles revealed significant
increases of IFN-gamma, IL-4 and IL-17, while no significant changes were
detected in TGF-beta1. Additionally, we found that pVAX-ESA10 enhanced the
activation of CD4(+) and CD8(+) T cells and the expression of MHC-I and MHC-II
molecules in spleen in mice. Immunization with pVAX-ESA10 significantly prolonged
survival time (14.3 +/- 1.7 days) after challenge infection with the virulent T.
gondii RH strain, compared with the control groups which died within 8 days.
These results suggested that TgESA10 DNA vaccine could trigger strong humoral and
cellular responses and induce partial protection against acute toxoplasmosis.
PMID- 26421597
TI - Preferences for end-of-life care among community-dwelling older adults and
patients with advanced cancer: A discrete choice experiment.
AB - Singapore is in the midst of several healthcare reforms in efforts to finance and
deliver health services for a rapidly aging population. The primary focus of
these reforms is to make healthcare services, including those at the end of life
(EOL), affordable. Given the increasingly high health care costs at the EOL,
policy makers need to consider how best to allocate resources. One strategy is to
allocate resources based on the preferences of sub-populations most likely to be
affected. This paper thus aims to quantify preferences for EOL care both among
community dwelling older adults (CDOAs) and among patients with a life-limiting
illness. A discrete choice experiment was administered to CDOAs and advanced
cancer patients in Singapore and willingness to pay (WTP) for specific EOL
improvements was estimated. We find that patients have a higher WTP for nearly
all EOL attributes compared with CDOAs. We also show that, for both groups,
moderate life extension is not the most important consideration; WTP for one
additional life year is lower than common thresholds for cost-effectiveness.
Irrespective of whose preference are considered, the results highlight the
importance of pain management and supporting home deaths at the EOL, perhaps at
the expense of public funding for costly but only marginally effective
treatments.
PMID- 26421598
TI - Health workforce planning and service expansion during an economic crisis: A case
study of the national breast screening programme in Ireland.
AB - This article aims to estimate the workforce and resource implications of the
proposed age extension of the national breast screening programme, under the
economic constraints of reduced health budgets and staffing levels in the Irish
health system. Using a mixed method design, a purposive sample of 20 participants
were interviewed and data were analysed thematically (June-September 2012).
Quantitative data (programme-level activity data, screening activity, staffing
levels and screening plans) were used to model potential workload and resource
requirements. The analysis indicates that over 90% operational efficiency was
achieved throughout the first six months of 2012. Accounting for maternity leave
(10%) and sick leave (3.5%), 16.1 additional radiographers (whole time
equivalent) would be required for the workload created by the age extension of
the screening programme, at 90% operational efficiency. The results suggest that
service expansion is possible with relatively minimal additional radiography
resources if the efficiency of the skill mix and the use of equipment are
improved. Investing in the appropriate skill mix should not be limited to
clinical groups but should also include administrative staff to manage and
support the service. Workload modelling may contribute to improved health
workforce planning and service efficiency.
PMID- 26421599
TI - First-Trimester Placental Growth Factor in Screening for Gestational Diabetes.
AB - OBJECTIVE: The aim of this study was first to assess whether first-trimester
serum concentrations of placental growth factor (PlGF) differ between patients
with and without gestational diabetes (GDM) and second to test whether there is a
correlation between glycosylated hemoglobin (HbA1c), a factor recently shown to
be useful in predicting GDM, and PlGF. METHODS: PlGF was measured at 8-14 weeks
with the Kryptor Immunoassay Analyzer (Brahms, Berlin, Germany). Absolute values
were converted to multiples of the median using the software provided by the
Fetal Medicine Foundation London. GDM was diagnosed using internationally
accepted criteria. HbA1c levels were quantified using the TOSOH G7 automated
hemoglobin analyzer. RESULTS: From January to December 2014, 328 women were
included in the study, 51 (15.5%) of whom developed GDM. First-trimester PlGF
quantification does not discriminate between women at risk to develop GDM and
controls, while HbA1c is able to do so. No correlation was found between PlGF and
HbA1c. CONCLUSION: Our findings do not lend support to the hypothesis that early
PlGF values are different in women who later develop GDM.
PMID- 26421600
TI - Irrigation and Debridement Before a 2-Stage Revision Total Knee Arthroplasty Does
Not Increase Risk of Failure.
AB - BACKGROUND: Studies have suggested that the success of 2-stage revision total
knee arthroplasty (rTKA) may be compromised by a prior failed irrigation and
debridement (I&D). The purpose of this study was to use 2 large state inpatient
databases to compare the 2-stage rTKA failure rates for those patients with and
without a prior I&D. METHODS: This retrospective, longitudinal study used
inpatient discharge data from the State Inpatient Database of 2 states
(California and New York) from 2005 to 2011. A combination of International
Classification of Diseases, Ninth Revision, diagnosis and procedure codes was
used to identify rTKA patients and compare failure rates for rTKA patients with
and without prior I&D. The primary outcome was failure of the staged revision,
which was defined as subsequent surgery due to infection within 4 years of the 2
stage rTKA. RESULTS: Of the 750 patients who underwent 2-stage rTKA, 57 had
undergone a prior I&D. In all, 126 patients failed rTKA. After 4 years, the
estimated failure rate was 8.7% (95% confidence interval [CI], 1.9%-16.9%) in the
group with prior I&D and 17.5% (95% CI, 14.7%-20.4%) in the group without prior
I&D. After adjusting for sex, race, insurance, median household income, and
comorbidities, the hazard ratio for the group with a failed I&D was 0.49 (P =
.122; 95% CI, 0.20-1.20), which indicated a lower risk of failure compared to the
group without prior I&D. CONCLUSION: These findings indicate that the failure
rate of 2-stage rTKA is not increased by prior failed I&D.
PMID- 26421601
TI - The Use of Hyaluronic Acid and Corticosteroid Injections Among Medicare Patients
With Knee Osteoarthritis.
AB - INTRODUCTION: Hyaluronic acid (HA) and corticosteroid (CS) injections are
frequently used in the management of osteoarthritis (OA) of the knee, despite a
lack of strong evidence supporting their efficacy in the literature. The purpose
of this study is to evaluate trends in HA and CS usage in Medicare patients over
the past 15 years. METHODS: The Medicare 5% national sample database was used to
identify 581,022 patients (representing an estimated 11.6 million) with a
diagnosis of knee OA between 1999 and 2013. RESULTS: The percentage of newly
diagnosed knee OA patients who received any injection trended from 39% in 1999 to
47% in 2006 and then declined to 37.5% in 2013. However, the mean number of
injections per newly diagnosed OA patient nearly doubled from 0.27 to 0.45 for CS
and from 0.18 to 0.36 for HA. Among those having both HA and CS injections, 69%
had CS as first-line treatment, whereas 31% had HA first. CONCLUSION: The
percentage of newly diagnosed knee OA patients receiving injections peaked in
2007 and then decreased steadily through 2013, as did the proportion of patients
receiving HA injections as first-line therapy. However, the number of injections
per patient has increased significantly over the past 15 years in both groups.
PMID- 26421602
TI - Editorial overview: Pharmaceutical biotechnology: Expanding horizons for
pharmaceutical biotechnology in industry and academia.
PMID- 26421603
TI - Social casino gaming and adolescents: Should we be concerned and is regulation in
sight?
AB - While gambling has traditionally been viewed as an adult activity, there is a
growing body of research that a significant number of adolescents are not only
gambling but are experiencing gambling related problems. As ease of access via
Internet wagering has increased, so too have some of the concomitant problems.
Social casino gambling, often thought of gambling without risking one's money
through the use of virtual currency, has become increasingly popular. The current
review examines whether we should be concerned over its widespread use and
whether such social games should be regulated.
PMID- 26421604
TI - Biomechanical investigations of the expanded platform-switching concept in
immediately loaded small diameter implants.
AB - STATEMENT OF PROBLEM: Use of a small diameter implant may increase the stress on
bone around the implant neck; however, an expanded platform design may mitigate
these stress concentrations. To date, no study has compared the biomechanical
effect of regular platform and extended platform designs on an implant. PURPOSE:
The purpose of this in vitro study was to evaluate the biomechanical effects of
an expanded platform-switching design for immediately loaded small diameter
implants on bone strains. MATERIAL AND METHODS: Three groups of artificial
jawbone models were prepared for small diameter (3.25-mm) and standard diameter
(4.0-mm) implants with expanded or regular platform designs. Platform-switching
implant design was implemented by assembling implants with a smaller connected
abutment. Specimens were tested under both vertical and lateral static loads at
190 N. Peak values of the principal microstrain of bone were recorded and
analyzed statistically with Kruskal-Wallis test and multiple comparisons
Bonferroni test (alpha=.05). The initial stability of each implant was also
measured for 3 types of implant. RESULTS: Under vertical loading, the bone strain
was lowest for the regular type of immediately loaded small diameter implant.
Under lateral loading, peak bone strain around the expanded platform small
diameter implant with platform switched abutment was up to 74.9% lower than that
of the regular type of small diameter implant. Increasing the implant diameter
from 3.25 mm to 4.0 mm on the expanded platform implants reduced the bone strain
by approximately 10% and 30% under lateral and vertical loading, respectively.
The initial implant stability did not vary significantly among the implants
tested. CONCLUSIONS: Using the expanded platform small diameter implant with a
platform-switched abutment may decrease the marginal bone strains around
immediately loaded small-diameter implants under lateral loading.
PMID- 26421606
TI - Study of lip print types among Nigerians.
AB - Lip prints in a narrow sense are normal lines and fissures in the form of
wrinkles and grooves present in the zone of transition of lips. The aims of this
study were to determine the types and association of lip prints as well as the
role of the lip print as genetic marker in ethnic differentiation in multi-ethnic
population of Nigeria. A total of 820 individuals (414 males and 406 females)
participated. The study sample was drawn from different ethnic groups of Nigeria.
The three major ethnic groups were identified and the minor groups were lumped
together. This was to provide clear evidence on the ethnic differentiation based
on lip print types among Nigerians. The lip prints were collected on microscopic
glass slides and developed using carbon black powder. Each print was then divided
into 10 compartments and analyzed using a magnifying lens. Chi-squared test was
used for association between ethnicity and lip print types; p<0.05 was set as a
level of significance. The result of the study showed the following lip print
pattern in Nigerian population where Type V (31.39%) was predominant, followed by
Type III (24.18%), Type IV (18.70%), Type I (14.87%), Type II (10.29%) and least
frequent was Type I' (0.57%). Statistically significant association (p<0.05) of
lip print types with ethnicity was found in upper left lateral compartments
(ULL). It was concluded that lip prints show ethnic differences. Hence, they may
hold potential promise as a supplementary tool in ethnic differentiation and in
personal identification.
PMID- 26421605
TI - Characterization of Vertical Accelerations Experienced by Older People Attending
an Aerobics Class Designed to Produce High Impacts.
AB - The purpose of this study was to establish the feasibility of using an aerobics
class to produce potentially bone protective vertical impacts of >= 4g in older
adults and to determine whether impacts can be predicted by physical function.
Participants recruited from older adult exercise classes completed an SF-12
questionnaire, short physical performance battery, and an aerobics class with
seven different components, performed at low and high intensity. Maximum g and
jerk values were identified for each activity. Forty-one participants (mean 69
years) were included. Mean maximal values approached or exceeded the 4g threshold
for four of the seven exercises. In multivariate analyses, age (-0.53; -0.77,
0.28) (standardized beta coefficient; 95% CI) and 4-m walk time (-0.39; -0.63,
0.16) were inversely related to maximum g. Aerobics classes can be used to
produce relatively high vertical accelerations in older individuals, although the
outcome is strongly dependent on age and physical function.
PMID- 26421607
TI - A case of semi-combusted pregnant female in the Phoenician-Punic necropolis of
Monte Sirai (Carbonia, Sardinia, Italy).
AB - We present a case of a pregnant woman with the fetus skeletal remains in situ,
belonging to the Phoenician-Punic necropolis of Monte Sirai (Sardinia, Italy).
The burial dates back to the late 6th to early 5th century BCE. Of the unborn
fetal cases documented in the literature this is amongst the oldest four and it
represents the first documented case of a pregnant woman in the Phoenician and
Punic necropolis literature. A physico-chemical investigation of bones combining
X-ray diffraction and Fourier transform-infrared spectroscopy suggests that the
female skeleton and fetus were subjected to an incomplete heat treatment
according to a funerary practice, perhaps limited to the period of early 5th
century BCE, that appears to be peculiar to this site.
PMID- 26421609
TI - Copper-Catalyzed Electrophilic Amination of Heteroarenes via C-H Alumination.
AB - A highly efficient Cu-catalyzed electrophilic amination reaction of readily
available heteroarenes with O-benzoyl hydroxylamines via a one-pot C-H
alumination is reported. The reactions were catalyzed using 1 mol % of CuCl to
afford various heteroaryl amines in good to excellent yields. The direct C-H
lithiation/transalumination of heteroarenes and catalytic amination sequence can
be performed in a single vessel on gram scales.
PMID- 26421608
TI - Arthroscopic treatment of septic arthritis of the knee in children.
AB - INTRODUCTION: Childhood septic arthritis of the knee is a serious disease that
can impair growth and cause serious functional sequelae. There are few data on
arthroscopic treatment in children, and series were always less than 20 cases.
HYPOTHESIS: The objective of this study was to assess clinical and radiographic
results of arthroscopic drainage combined with antibiotic therapy for the
treatment of childhood septic arthritis of the knee. The hypothesis was that
arthroscopic treatment is also effective in children. MATERIALS AND METHODS: A
retrospective study, conducted between January 2003 and December 2012, included
patients under 15 years of age with septic arthritis of the knee treated by
arthroscopic drainage with a minimum of 2 years' follow-up. RESULTS: Fifty-six
patients, with a mean age at surgery of 3.4 years (range, 3 months to 12 years),
were included. Staphylococcus aureus was the most common causative organism. Two
patients (3.6%) had recurrence, successfully treated by repeat arthroscopic
drainage. Mean Lysholm score was 96.9 (range, 70-100) and mean KOOS-Child pain,
symptoms, daily life, sports and quality of life scores were respectively 97 (81
100), 95 (75-100), 98 (89-100), 93 (71-100) and 95 (70-100) at a mean 65 months'
follow-up. Ranges of motion were normal. Radiology found no joint damage.
DISCUSSION AND CONCLUSION: Arthroscopic drainage combined with antibiotic
treatment is a simple and effective treatment for childhood septic arthritis of
the knee and is for our reference attitude. It can also be indicated in case of
recurrence. LEVEL OF EVIDENCE: IV, retrospective study.
PMID- 26421610
TI - Optimization of the steam explosion and enzymatic hydrolysis for sugars
production from oak woods.
AB - Fermentable sugars production from three kind of steam-exploded oak wood was
optimized by Response Surface Methodology (RSM), using the severity factor (R0),
the pretreated total solids (TS%) and the enzyme loading (EL%) as variables of a
central composite design. A total of 17 experiments for each biomass were carried
out. The optimal conditions established with RSM were: severity, 4.46 for holm,
4.03 for turkey oak and 3.92 for downey oak; total solids, 5.4% for holm, 5.0%
for turkey oak and 12.7% for downey oak; and enzyme concentration, 9.6% for holm,
15.0% for turkey oak and 15.0% for downey oak. Under these conditions, the model
predicted an overall sugar yield of 67.1% for holm, 79.9% for turkey oak and
68.4% for downey oak. The results of the confirmation experiments under optimal
conditions agreed well with model predictions. Oak wood species may be a good
feedstock for the production of reducing sugars.
PMID- 26421611
TI - The Origin and Diversity of Cpt1 Genes in Vertebrate Species.
AB - The Carnitine palmitoyltransferase I (Cpt1) gene family plays a crucial role in
energy homeostasis since it is required for the occurrence of fatty acid beta
oxidation in the mitochondria. The exact gene repertoire in different vertebrate
lineages is variable. Presently, four genes are documented: Cpt1a, also known as
Cpt1a1, Cpt1a2; Cpt1b and Cpt1c. The later is considered a mammalian innovation
resulting from a gene duplication event in the ancestor of mammals, after the
divergence of sauropsids. In contrast, Cpt1a2 has been found exclusively in
teleosts. Here, we reassess the overall evolutionary relationships of Cpt1 genes
using a combination of approaches, including the survey of the gene repertoire in
basal gnathostome lineages. Through molecular phylogenetics and synteny studies,
we find that Cpt1c is most likely a rapidly evolving orthologue of Cpt1a2. Thus,
Cpt1c is present in other lineages such as cartilaginous fish, reptiles,
amphibians and the coelacanth. We show that genome duplications (2R) and variable
rates of sequence evolution contribute to the history of Cpt1 genes in
vertebrates. Finally, we propose that loss of Cpt1b is the likely cause for the
unusual energy metabolism of elasmobranch.
PMID- 26421612
TI - Characterization of Bacterial, Archaeal and Eukaryote Symbionts from Antarctic
Sponges Reveals a High Diversity at a Three-Domain Level and a Particular
Signature for This Ecosystem.
AB - Sponge-associated microbial communities include members from the three domains of
life. In the case of bacteria, they are diverse, host specific and different from
the surrounding seawater. However, little is known about the diversity and
specificity of Eukarya and Archaea living in association with marine sponges.
This knowledge gap is even greater regarding sponges from regions other than
temperate and tropical environments. In Antarctica, marine sponges are abundant
and important members of the benthos, structuring the Antarctic marine ecosystem.
In this study, we used high throughput ribosomal gene sequencing to investigate
the three-domain diversity and community composition from eight different
Antarctic sponges. Taxonomic identification reveals that they belong to families
Acarnidae, Chalinidae, Hymedesmiidae, Hymeniacidonidae, Leucettidae,
Microcionidae, and Myxillidae. Our study indicates that there are different
diversity and similarity patterns between bacterial/archaeal and eukaryote
microbial symbionts from these Antarctic marine sponges, indicating inherent
differences in how organisms from different domains establish symbiotic
relationships. In general, when considering diversity indices and number of phyla
detected, sponge-associated communities are more diverse than the planktonic
communities. We conclude that three-domain microbial communities from Antarctic
sponges are different from surrounding planktonic communities, expanding previous
observations for Bacteria and including the Antarctic environment. Furthermore,
we reveal differences in the composition of the sponge associated bacterial
assemblages between Antarctic and tropical-temperate environments and the
presence of a highly complex microbial eukaryote community, suggesting a
particular signature for Antarctic sponges, different to that reported from other
ecosystems.
PMID- 26421613
TI - Temporal Structure of Human Gaze Dynamics Is Invariant During Free Viewing.
AB - We investigate the dynamic structure of human gaze and present an experimental
study of the frequency components of the change in gaze position over time during
free viewing of computer-generated fractal images. We show that changes in gaze
position are scale-invariant in time with statistical properties that are
characteristic of a random walk process. We quantify and track changes in the
temporal structure using a well-defined scaling parameter called the Hurst
exponent, H. We find H is robust regardless of the spatial complexity generated
by the fractal images. In addition, we find the Hurst exponent is invariant
across all participants, including those with distinct changes to higher order
visual processes due to neural degeneration. The value we find for H of 0.57
shows that the gaze dynamics during free viewing of fractal images are consistent
with a random walk process with persistent movements. Our research suggests the
human visual system may have a common strategy that drives the dynamics of human
gaze during exploration.
PMID- 26421614
TI - Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is
Associated with Poor Prognosis.
AB - BACKGROUND: The epithelioid and sarcomatoid histologic variants of malignant
pleural mesothelioma (MPM) can be considered as E- and M-parts of the epithelial
mesenchymal transition (EMT) axis; the biphasic being an intermediate. EMT is
associated with an increase of stem cell (SC) traits. We correlated the neural
crest SC marker nestin and the EMT marker periostin with histology, type of neo
adjuvant chemotherapy (CT) and overall survival (OS) of MPM patients. PATIENTS
AND METHODS: Tumor tissues of a historic cohort 1 (320 patients) and an intended
induction chemotherapy followed by extrapleural pneumonectomy (EPP) cohort 2 (145
patients) were immunohistochemically H-scored (intensity of immunoreactivity
multiplied by frequency of stained cells). Paired chemo-naive biopsies and
treated surgical specimens were available for 105/145 patients. CT included
platinum/gemcitabine (Pla/Gem) or platinum/pemetrexed (Pla/Pem). RESULTS:
Expression of any cytosolic nestin progressively increased from epithelioid to
biphasic to sarcomatoid MPM in cohort 1, whereas the diagnostic markers
calretinin and podoplanin decreased. In cohort 2, Pla/Pem CT increased the
expression level of nestin in comparison to Pla/Gem, whereas the opposite was
found for periostin. In Pla/Pem treated patients, nestin was higher in biphasic
MPM compared to epithelioid. In addition to non-epithelioid histology, any
expression of nestin in chemo-naive biopsies (median overall survival: 22 vs. 17
months) and chemo-treated surgical specimens (18 vs. 12 months) as well as high
periostin in biopsies (23 vs. 15 months) were associated with poor prognosis. In
the multivariate survival analysis, any nestin expression in chemo-naive biopsies
proved to be an independent prognosticator against histology. In both pre- and
post-CT situations, the combination of nestin or periostin expression with non
epithelioid histology was particularly/ dismal (all p-values <0.05). CONCLUSIONS:
The SC marker nestin and the EMT marker periostin allow for further prognostic
stratification among histologic variants of MPM. Their expression level is
influenced by neo-adjuvant chemotherapy.
PMID- 26421616
TI - Probabilistic Analysis of Pattern Formation in Monotonic Self-Assembly.
AB - Inspired by biological systems, self-assembly aims to construct complex
structures. It functions through piece-wise, local interactions among component
parts and has the potential to produce novel materials and devices at the
nanoscale. Algorithmic self-assembly models the product of self-assembly as the
output of some computational process, and attempts to control the process of
assembly algorithmically. Though providing fundamental insights, these
computational models have yet to fully account for the randomness that is
inherent in experimental realizations, which tend to be based on trial and error
methods. In order to develop a method of analysis that addresses experimental
parameters, such as error and yield, this work focuses on the capability of
assembly systems to produce a pre-determined set of target patterns, either
accurately or perhaps only approximately. Self-assembly systems that assemble
patterns that are similar to the targets in a significant percentage are "strong"
assemblers. In addition, assemblers should predominantly produce target patterns,
with a small percentage of errors or junk. These definitions approximate notions
of yield and purity in chemistry and manufacturing. By combining these
definitions, a criterion for efficient assembly is developed that can be used to
compare the ability of different assembly systems to produce a given target set.
Efficiency is a composite measure of the accuracy and purity of an assembler.
Typical examples in algorithmic assembly are assessed in the context of these
metrics. In addition to validating the method, they also provide some insight
that might be used to guide experimentation. Finally, some general results are
established that, for efficient assembly, imply that every target pattern is
guaranteed to be assembled with a minimum common positive probability, regardless
of its size, and that a trichotomy exists to characterize the global behavior of
typical efficient, monotonic self-assembly systems in the literature.
PMID- 26421617
TI - Fourier Spot Volatility Estimator: Asymptotic Normality and Efficiency with
Liquid and Illiquid High-Frequency Data.
AB - The recent availability of high frequency data has permitted more efficient ways
of computing volatility. However, estimation of volatility from asset price
observations is challenging because observed high frequency data are generally
affected by noise-microstructure effects. We address this issue by using the
Fourier estimator of instantaneous volatility introduced in Malliavin and Mancino
2002. We prove a central limit theorem for this estimator with optimal rate and
asymptotic variance. An extensive simulation study shows the accuracy of the spot
volatility estimates obtained using the Fourier estimator and its robustness even
in the presence of different microstructure noise specifications. An empirical
analysis on high frequency data (U.S. S&P500 and FIB 30 indices) illustrates how
the Fourier spot volatility estimates can be successfully used to study intraday
variations of volatility and to predict intraday Value at Risk.
PMID- 26421615
TI - Ammonia Affects Astroglial Proliferation in Culture.
AB - Primary cultures of rat astroglial cells were exposed to 1, 3 and 5 mM NH4Cl for
up to 10 days. Dose- and time-dependent reductions in cell numbers were seen,
plus an increase in the proportion of cells in the S phase. The DNA content was
reduced in the treated cells, and BrdU incorporation diminished. However, neither
ammonia nor ammonia plus glutamine had any effect on DNA polymerase activity.
iTRAQ analysis showed that exposure to ammonia induced a significant reduction in
histone and heterochromatin protein 1 expression. A reduction in cell viability
was also noted. The ammonia-induced reduction of proliferative activity in these
cultured astroglial cells seems to be due to a delay in the completion of the S
phase provoked by the inhibition of chromatin protein synthesis.
PMID- 26421618
TI - The Role of Electrostatic Interactions in Binding of Histone H3K4me2/3 to the
Sgf29 Tandem Tudor Domain.
AB - Several reader domain proteins that specifically recognize methyllysine
containing histones contain the negatively-charged aspartate or glutamate
residues as part of the aromatic cage. Herein, we report thermodynamic analyses
for the recognition of histone H3K4me3 and H3K4me2 by the tandem tudor domain of
Sgf29 and its recognition site variants. Small uncharged and large aromatic
substitutions on the Asp266 site resulted in a significant decrease in binding
affinities for both H3K4me3 and H3K4me2, demonstrating the role of the negative
charge of Asp266 in the readout process by Sgf29. This study emphasizes the
essential contribution of electrostatic interactions to the overall binding
affinity, and reveals that the underlying mechanisms for the recognition of
Kme2/3 depend on the composition and arrangement of the aromatic cage.
PMID- 26421619
TI - Evolutionary Changes of Hepatitis B Virus Pre-S Mutations Prior to Development of
Hepatocellular Carcinoma.
AB - BACKGROUND AND AIMS: Deletions/mutations in the hepatitis B virus (HBV) pre-S
region have been associated with hepatocellular carcinoma (HCC). We aimed to
study the evolutionary changes of pre-S mutations prior to HCC development.
METHODS: We studied the HBV pre-S sequences at 1 to 10 years preceding diagnosis
of HCC in 74 patients with HBV-related HCC (HCC group). 148 chronic hepatitis B
patients matched for sex and age in 2:1 ratio, who had been followed up for at
least 3 years without HCC (HCC-free group) were recruited as controls. 56 and 47
patients of HCC and HCC-free groups respectively had serially stored sera for
longitudinally examination at 1-3 years, 4-6 years, 7-9 years and >=10 years
prior to the recruitment of the study. RESULTS: Compared to the HCC-free group,
higher frequencies of pre-S deletions and point mutations (at 11 codons) were
observed in the HCC group (p<0.05). Multiple logistic regression analysis showed
that pre-S deletions, point mutations at codon 51 and 167 were independent
factors associated with HCC. Longitudinal observation showed that pre-S deletions
and most of the 11 HCC-associated pre-S point mutations existed at least 10 years
before HCC development, and were more prevalent preceding HCC development in
patients from HCC groups than HCC-free group. The number of HCC-associated pre-S
point mutations increased over time preceding HCC development, and correlated
positively with the time to HCC diagnosis (r = 0.220, p = 0.005). CONCLUSIONS:
High prevalence and cumulative evolution of pre-S mutations preceding HCC
development suggested a possible carcinogenic role of pre-S mutations and their
potential application in HCC risk prediction.
PMID- 26421620
TI - Risk of Major Cardiovascular Events in People with Down Syndrome.
AB - BACKGROUND: Improved medical care over more than five decades has markedly
increased life expectancy, from 12 years to approximately 60 years, in people
with Down syndrome (DS). With increased survival into late adulthood, there is
now a greater need for the medical care of people with DS to prevent and treat
aging-related disorders. In the wider population, acquired cardiovascular
diseases such as stroke and coronary heart disease are common with increasing
age, but the risks of these diseases in people with DS are unknown. There are no
population-level data on the incidence of acquired major cerebrovascular and
coronary diseases in DS, and no data examining how cardiovascular comorbidities
or risk factors in DS might impact on cardiovascular event incidence. Such data
would be also valuable to inform health care planning for people with DS. Our
objective was therefore to conduct a population-level matched cohort study to
quantify the risk of incident major cardiovascular events in DS. METHODS AND
FINDINGS: A population-level matched cohort study compared the risk of incident
cardiovascular events between hospitalized patients with and without DS,
adjusting for sex, and vascular risk factors. The sample was derived from
hospitalization data within the Australian state of Victoria from 1993-2010. For
each DS admission, 4 exact age-matched non-DS admissions were randomly selected
from all hospitalizations within a week of the relevant DS admission to form the
comparison cohort. There were 4,081 people with DS and 16,324 without DS, with a
total of 212,539 person-years of observation. Compared to the group without DS,
there was a higher prevalence in the DS group of congenital heart disease,
cardiac arrhythmia, dementia, pulmonary hypertension, diabetes and sleep apnea,
and a lower prevalence of ever-smoking. DS was associated with a greater risk of
incident cerebrovascular events (Risk Ratio, RR 2.70, 95% CI 2.08, 3.53)
especially among females (RR 3.31, 95% CI 2.21, 4.94) and patients aged <= 50
years old. The association of DS with ischemic strokes was substantially
attenuated on adjustment for cardioembolic risk (RR 1.93, 95% CI 1.04, 3.20), but
unaffected by adjustment for atherosclerotic risk. DS was associated with a 40
70% reduced risk of any coronary event in males (RR 0.58, 95% CI 0.40, 0.84) but
not in females (RR 1.14, 95% CI 0.73, 1.77). CONCLUSIONS: DS is associated with a
high risk of stroke, expressed across all ages. Ischemic stroke risk in DS
appears mostly driven by cardioembolic risk. The greater risk of hemorrhagic
stroke and lower risk of coronary events (in males) in DS remain unexplained.
PMID- 26421621
TI - Organophosphate pesticide method development and presence of chlorpyrifos in the
feet of nearctic-neotropical migratory songbirds from Canada that over-winter in
Central America agricultural areas.
AB - Recent modeling analysis suggests that numerous birds may be at risk of acute
poisoning in insecticide-treated fields. Although the majority of avian field
studies on pesticides have focused on treated seed, granule, insect or vegetation
(oral exposure) ingestion, dermal exposure is an important exposure route when
birds come into contact with deposited pesticides on foliage and other surfaces.
Some nearctic-neotropical migratory songbirds are likely exposed to pesticides on
their non-breeding habitats and include treated crops, plantations or farmlands.
In the present study, we developed a method for four environmentally-relevant
organophosphate (OP) pesticides (fenthion, fenamiphos, chlorpyrifos and diazinon)
in the feet of migratory songbirds (i.e. Common yellowthroat, Gray catbird,
Indigo bunting, America redstart, Northern waterthrush, Northern parula, and an
additional 12 species of warblers). A total of 190 specimens of the 18 species of
songbirds were sampled from available window-killed birds (spring of 2007 and
2011) in downtown Toronto, Canada. The species that were available most likely
over-wintered in Mexican/Central American crops such as citrus, coffee and cacao.
The feet of the dead birds were sampled and where OP foot exposure likely
occurred during over-wintering foraging on pesticide-treated crops. Chlorpyrifos
was the only measurable OP (pg mg feet weight(-1)) and in the 2011-collected feet
of Black throated blue warbler (0.5), Tennessee warbler (1.0), Northern parula
(1.2), Northern waterthrush (0.6), Common yellowthroat (1.0) and the Blue winged
warbler (0.9). Dermal contact with OP pesticides during over-wintering in
agricultural areas resulted in low levels of chlorpyrifos and long time retention
on the feet of a subset of songbirds.
PMID- 26421622
TI - Degradation of organic dyes by Si/SiOx core-shell nanowires: Spontaneous
generation of superoxides without light irradiation.
AB - Recently, silicon nanowires (SiNWs) have been proven to be highly active in the
photocatalysis of dye degradation. However, the unstable hydrogen-terminated
surface and the need for constant light irradiation hinder their extensive use.
In this work, a stable silica shell was intentionally formed on the surface of
SiNWs to produce Si/SiOx core-shell silicon nanowires (S-SiNWs). Light
illuminated or not, S-SiNWs showed almost identical degradation ability for the
degradation of indigo carmine (IC) in both conditions, which meant neither
hydrogen termination nor light irradiation was a prerequisite for the degradation
activity of S-SiNWs. UV/Vis spectroscopy and liquid chromatography/mass
spectrometry showed that IC was converted into isatin sulfonic acid in this
process. Quenching studies and electron paramagnetic resonance spectroscopy
revealed that this bleaching ability was highly dependent on superoxides. A
possible mechanism was accordingly suggested. In addition, the recently
discovered reductase-like activity of SiNWs can be explained by the superoxides
generation.
PMID- 26421624
TI - Low dietary levels of Al, Pb and Cd may affect the non-enzymatic antioxidant
capacity in caged honey bees (Apis mellifera).
AB - Several hypotheses have been proposed to explain the abnormally high mortality
rate observed in bee populations in Europe and North America. While studies based
on the effects of pesticides are paramount, the metals present in agroecosystems
are often overlooked. Sources of metals are linked to the nature of soils and to
agricultural practices, namely the use of natural or chemical nutrients as well
as residual materials from waste-water treatment sludge. The aim of this study
was to investigate the effects of metals on honey bees exposed for 10 days to
environmentally realistic concentrations of Al, Pb and Cd (dissolved in syrup).
The monitoring of syrup consumption combined with the quantification of metals in
bees revealed the following order for metal bioconcentration ratios: Cd > Pb >
Al. Alpha-tocopherol, metallothionein-like proteins (MTLPs) and lipid
peroxidation were quantified. When bees were exposed to increasing amounts of Cd,
a marked augmentation of MTLPs levels was found. Lead (Pb) and Cd caused an
increase in alpha-tocopherol content, while alteration of lipid peroxidation was
observed only with Al exposure. These findings raise concerns about the
bioavailability and the additional threat posed by metals for pollinators in
agricultural areas while providing new insights for potential use of the honey
bee as a sentinel species for metal exposure.
PMID- 26421623
TI - Potential application of a bioemulsifier-producing actinobacterium for treatment
of vinasse.
AB - Vinasse is a complex effluent created during production of ethyl alcohol, which
can present serious pollution hazard in areas where it is discharged. A variety
of technologies, many based upon recovery of the effluent via microbial pathways,
are continually being evaluated in order to mitigate the pollution potential of
vinasse. The present work reports on initial advances related to the
effectiveness of the actinobacterium Streptomyces sp. MC1 for vinasse treatment.
Alternative use of raw vinasse as a substrate for producing metabolites of
biotechnological interest such as bioemulsifiers, was also evaluated. The strain
was able to grow at very high vinasse concentrations (until 50% v/v) and remove
over 50% of the biodegradable organic matter in a time period as short as 4 d.
Potentially toxic metals such as Mn, Fe, Zn, As, and Pb were also effectively
removed during bacterial growth. Decrease in the pollution potential of treated
vinasse compared to raw effluent, was reflected in a significant increase in the
vigour index of Lactuca sativa (letucce) used as bioremediation indicator.
Finally, significant bioemulsifier production was detected when this strain was
incubated in a vinasse-based culture medium. These results represent the first
advances on the recovery and re-valuation of an actual effluent, by using an
actinobacterium from our collection of cultures.
PMID- 26421625
TI - Degradation of triclosan in aqueous solution by dielectric barrier discharge
plasma combined with activated carbon fibers.
AB - The degradation of triclosan (TCS) in aqueous solution by dielectric barrier
discharge (DBD) plasma with activated carbon fibers (ACFs) was investigated. In
this study, ACFs and DBD plasma coexisted in a planar DBD plasma reactor, which
could synchronously achieve degradation of TCS, modification and in situ
regeneration of ACFs, enhancing the effect of recycling of ACFs. The properties
of ACFs before and after modification by DBD plasma were characterized by BET and
XPS. Various processing parameters affecting the synergetic degradation of TCS
were also investigated. The results exhibited excellent synergetic effects in DBD
plasma-ACFs system on TCS degradation. The degradation efficiency of 120 mL TCS
with initial concentration of 10 mg L(-1) could reach 93% with 1 mm thick ACFs in
18 min at input power of 80 W, compared with 85% by single DBD plasma. Meanwhile,
the removal rate of total organic carbon increased from 12% at pH 6.26-24% at pH
3.50. ACFs could ameliorate the degradation efficiency for planar DBD plasma when
treating TCS solution at high flow rates or at low initial concentrations. A
possible degradation pathway of TCS was investigated according to the detected
intermediates, which were identified by liquid chromatography-hybrid quadrupole
time-of-flight mass spectrometry (LC-QTOF-MS) combined with theoretical
calculation of Gaussian 09 program.
PMID- 26421626
TI - Ecotoxicological analysis during the removal of carbofuran in fungal bioaugmented
matrices.
AB - Biomixtures are used for the removal of pesticides from agricultural wastewater.
As biomixtures employ high content of lignocellulosic substrates, their
bioaugmentation with ligninolytic fungi represents a novel approach for their
enhancement. Nonetheless, the decrease in the concentration of the pesticide may
result in sublethal concentrations that still affect ecosystems. Two matrices, a
microcosm of rice husk (lignocellulosic substrate) bioaugmented with the fungus
Trametes versicolor and a biomixture that contained fungally colonized rice husk
were used in the degradation of the insecticide/nematicide carbofuran (CFN).
Elutriates simulating lixiviates from these matrices were used to assay the
ecotoxicological effects at sublethal level over Daphnia magna (Straus) and the
fish Oreochromis aureus (Steindachner) and Oncorhynchus mykiss (Walbaum).
Elutriates obtained after 30 d of treatment in the rice husk microcosms at
dilutions over 2.5% increased the offspring of D. magna as a trade-off stress
response, and produced mortality of neonates at dilutions over 5%. Elutriates
(dilution 1:200) obtained during a 30 d period did not produce alterations on the
oxygen consumption and ammonium excretion of O. mykiss, however these
physiological parameters were affected in O. aureus at every time point of
treatment, irrespective of the decrease in CFN concentration. When the fungally
colonized rice husk was used to prepare a biomixture, where more accelerated
degradation is expected, similar alterations on the responses by O. aureus were
achieved. Results suggest that despite the good removal of the pesticide, it is
necessary to optimize biomixtures to minimize their residual toxicity and
potential chronic effects on aquatic life.
PMID- 26421627
TI - Copper toxicity and the influence of water quality of Dongnai River and Mekong
River waters on copper bioavailability and toxicity to three tropical species.
AB - The present study investigated copper (Cu) toxicity and the influence of water
quality characteristics of Dongnai River and Mekong River (Vietnam) surface
waters to three tropical species; Daphnia lumholtzi, Ceriodaphnia cornuta, and
Danio rerio. The river waters had a range of water quality parameters that modify
Cu bioavailability and toxicity. The range of total hardness, alkalinity, pH and
dissolved organic carbon were 15-64 mg/L as CaCO3, 18-58 mg/L as CaCO3, 6.62
7.88, and 6.9-14.7 mg/l, respectively. The US EPA acute toxicity test method with
a modification to the light photoperiod and temperature for tropical organisms
was used to investigate Cu toxicity. Result of the present study found that Cu
produced toxic effect to the studied organisms at low concentrations. The 48-h
LC50 ranged from 3.92 to 8.61 ug/l, 2.92-9.56 ug/l, and 15.71-68.69 ug/l
dissolved Cu for D. lumholtzi, C. cornuta, and D. rerio, respectively. In
general, water quality had an influence on Cu bioavailability and toxicity to the
studied organisms. The toxicity of Cu was higher in water with lower hardness,
DOC, and/or pH. The present study indicates a contribution of Cu hydroxide and
carbonate to Cu bioavailability to Mekong organisms. Results of the present study
will be used for calibrating the US Cu Biotic Ligand Model (BLM) to Mekong River
water and organisms in support of application of the BLM for setting site
specific Cu water quality guidelines in the ecosystem of the Lower Mekong River
Basin.
PMID- 26421628
TI - Sorption of hydrophobic organic compounds to a diverse suite of carbonaceous
materials with emphasis on biochar.
AB - Carbonaceous materials like biochars are increasingly recognized as effective
sorbent materials for sequestering organic pollutants. Here, we study sorption
behavior of two common hydrophobic organic contaminants 2,2',5,5'
tetrachlorobiphenyl (CB52) and phenanthrene (PHE), on biochars and other
carbonaceous materials (CM) produced at a wide range of conditions and
temperatures from various feedstocks. The primary aim was to establish structure
reactivity relationships responsible for the observed variation in CM and biochar
sorption characteristics. CM were characterized for their elemental composition,
surface area, pore size distribution, aromaticity and thermal stability.
Freundlich sorption coefficients for CB52 and PHE (i.e. LogK(F,CB52) and
K(F,PHE), respectively) to CM showed a variation of two to three orders of
magnitude, with LogK(F,CB52) ranging from 5.12 +/- 0.38 to 8.01 +/- 0.18 and
LogK(F,PHE) from 5.18 +/- 0.09 to 7.42 +/- 1.09. The highest LogK(F) values were
observed for the activated CM, however, non-activated biochars produced at high
temperatures (>700 degrees C) sorbed almost as strongly (within 0.2-0.5 Log
units) as the activated ones. Sorption coefficients significantly increased with
pyrolysis temperature, CM surface area and pore volume, aromaticity, and thermal
stability, and decreased with H/C, O/C, (O + N)/C content. The results of our
study contribute to the understanding of processes underlying HOC sorption to CM
and explore the potential of CM as engineered sorbents for environmental
applications.
PMID- 26421629
TI - A facile and novel strategy to synthesize reduced TiO2 nanotubes photoelectrode
for photoelectrocatalytic degradation of diclofenac.
AB - TiO2 nano-materials have been considered as a versatile candidate for the
photoelectrochemical (PECH) applications. In this study, we reported a facile and
novel strategy to synthesize reduced TiO2 nanotubes (TiO2 NTs) photoelectrode.
The microwave reduction could introduce oxygen vacancy in the lattice of TiO2,
while the rapid-production of oxygen vacancy facilitated the generation of
impurity level between the forbidden band and greatly enhancement of visible
light absorption, thereby resulting in an improved separation efficiency of
photogenerated charge carriers and photocatalytic (PC) performance. Additionally,
the derived valence band X-ray photoelectron spectroscopy (VBXPS) and
photoluminescence (PL) spectra confirmed the existence of oxygen vacancy in the
lattice of TiO2 NTs photoelectrode, in which the valence bond maximum (VBM) and
charge carriers concentration of reduced TiO2 NTs photoelectrode was determined
to be 1.75 eV and 5.36 * 10(19) cm(-3), respectively. Furthermore, the scavenging
experiments revealed that .OH radical was the dominated species for the
degradation of diclofenac. The enhanced-visible-light PC mechanism could mainly
be attributed to the generation of oxygen vacancy, which can provide not only the
visible light absorption capacity but also charge separation efficiency.
PMID- 26421630
TI - Characteristics and influencing factors of tetrachloroethylene sorption
desorption on soil and its components.
AB - To investigate the effects of soil structure, soil organic carbon (SOC),
minerals, initial tetrachloroethylene (PCE) concentration (C0), and ionic
strength (Ci) on PCE sorption-desorption, six types of soil were adopted as
adsorbents, including two types of natural soil and four types of soil with most
of the "soft carbon" pre-treated by H2O2 or with all SOC removed from the
original soil by 600 degrees C ignition. The results showed that all of the
sorption-desorption isotherms of PCE were non-linear within the experimental
range, and the H2O2-treated samples exhibited higher non-linear sorption
isotherms than those of the original soils. The hysteresis index of PCE sorption
to original soil is less pronounced than that of the H2O2-treated and 600
degrees C-heated samples due to the entrapment of sorbate molecules in the "hard
carbon" domain, together with the meso- and microporous structures within the 600
degrees C-heated samples. Both SOC and minerals have impacts on the sorption
desorption of PCE, and the sorption-desorption contribution rate of minerals
increased with decreasing SOC content. C0 has almost no influence on the sorption
to minerals of the soils, but the contribution rate of minerals decreased with
increasing C0 in the desorption stage. As a result of the salting-out effect, PCE
sorption capacity was increased by increasing Ci, especially when Ci >= 0.1 M.
Moreover, desorption increased and hysteresis weakened with increasing Ci, except
for the 600 degrees C-heated samples. In addition, no significant effect of Ci
on desorption of PCE and no hysteresis was observed in this experimental range
for the 600 degrees C-heated samples.
PMID- 26421631
TI - Surface doping of La ions into ZnO nanocrystals to lower the optimal working
temperature for HCHO sensing properties.
AB - Lowering the working temperature without sacrificing other good gas-sensing
properties is of particular interest to gas sensors for an excellent performance.
In this work, La surface doped ZnO nanocrystals were successfully prepared by a
facile thermal treatment with lanthanum nitrate (La(NO3)3) solution injected into
ZnO thick films, which exhibited a remarkable decrease in the optimal working
temperature for formaldehyde (HCHO) sensing properties. This was probably
attributed to the formation of surface LaZn defects in the ZnO nanocrystals which
was evidenced by XRD, XPS results and DFT calculations. The surface LaZn defects
can introduce a shallower donor level than oxygen vacancies, and probably
facilitate the charge transfer from oxygen species to ZnO for producing
chemisorbed oxygen species more easily. This was in good agreement with the DFT
results that the absorption energy of oxygen molecules on the surface of La doped
ZnO was only -10.61 eV, much lower than that of pure ZnO. Moreover, the optimal
working temperature of the La doped ZnO based sensor was significantly decreased
from 350 to 250 degrees C without sacrificing the high and quick response to
HCHO gas as the content of surface LaZn defects was increased gradually.
Therefore, the behavior of the surface LaZn defects in the optimal working
temperature revealed a HCHO response mechanism in ZnO, which can provide new
insights into the enhanced HCHO sensing performance of gas sensors.
PMID- 26421632
TI - Human fetal cardiac progenitors: The role of stem cells and progenitors in the
fetal and adult heart.
AB - The human fetal heart is formed early during embryogenesis as a result of cell
migrations, differentiation, and formative blood flow. It begins to beat around
gestation day 22. Progenitor cells are derived from mesoderm (endocardium and
myocardium), proepicardium (epicardium and coronary vessels), and neural crest
(heart valves, outflow tract septation, and parasympathetic innervation). A
variety of molecular disturbances in the factors regulating the specification and
differentiation of these cells can cause congenital heart disease. This review
explores the contribution of different cardiac progenitors to the embryonic heart
development; the pathways and transcription factors guiding their expansion,
migration, and functional differentiation; and the endogenous regenerative
capacity of the adult heart including the plasticity of cardiomyocytes. Unfolding
these mechanisms will become the basis for understanding the dynamics of specific
congenital heart disease as well as a means to develop therapy for fetal as well
as postnatal cardiac defects and heart failure.
PMID- 26421633
TI - Relativistic and Solvation Effects on the Stability of Gold(III) Halides in
Aqueous Solution.
AB - The redox stability of gold halide complexes in aqueous solution has been
examined quantum-chemically by a systematic comparison of scalar- and
nonrelativistic pseudopotential calculations, using both COSMO and D-COSMO-RS
solvent models for water. After a computational benchmarking of density
functional methods against CCSD(T) results for the gas phase decomposition AuX4(
) -> AuX2(-) + X2, B3LYP calculations have been used to establish solvent
contributions. While relativity clearly enhances the stability of AuX4(-) (X = F,
Cl, Br, I) complexes against X2 elimination, solvation favors the lower oxidation
state. Solvation and relativity are nonadditive, due to the relativistic
reduction of bond polarity. At scalar relativistic D-COSMO-RS level, the reaction
AuX4(-) ? AuX2(-) + X2 is computed to be endergonic, except for X = I, where it
is slightly exergonic. Under the chosen conditions, partial hydrolysis of AuCl4(
) to AuCl3OH(-) is exergonic. The latter complex in turn is stable against Cl2
elimination. The disproportionation 3 AuCl2(-) ? AuCl4(-) + 2 Au(s) + 2 Cl(-) is
clearly exergonic. All of the computed reaction energies at scalar relativistic D
COSMO-RS level agree well with the observed speciation in dilute pH-neutral
solutions at ambient temperatures.
PMID- 26421635
TI - Correlative Synchrotron Fourier Transform Infrared Spectroscopy and Single
Molecule Super Resolution Microscopy for the Detection of Composition and
Ultrastructure Alterations in Single Cells.
AB - Single molecule localization microscopy (SMLM) and synchrotron Fourier transform
infrared (S-FTIR) spectroscopy are two techniques capable of elucidating unique
and valuable biological detail. SMLM provides images of the structures and
distributions of targeted biomolecules at spatial resolutions up to an order of
magnitude better than the diffraction limit, whereas IR spectroscopy objectively
measures the holistic biochemistry of an entire sample, thereby revealing any
variations in overall composition. Both tools are currently applied extensively
to detect cellular response to disease, chemical treatment, and environmental
change. Here, these two techniques have been applied correlatively at the single
cell level to probe the biochemistry of common fixation methods and have detected
various fixation-induced losses of biomolecular composition and cellular
ultrastructure. Furthermore, by extensive honing and optimizing of fixation
protocols, many fixation artifacts previously considered pervasive and regularly
identified using IR spectroscopy and fluorescence techniques have been avoided.
Both paraformaldehyde and two-step glutaraldehyde fixation were identified as
best preserving biochemistry for both SMLM and IR studies while other
glutaraldehyde and methanol fixation protocols were demonstrated to cause
significant biochemical changes and higher variability between samples. Moreover,
the potential complementarity of the two techniques was strikingly demonstrated
in the correlated detection of biochemical changes as well as in the detection of
fixation-induced damage that was only revealed by one of the two techniques.
PMID- 26421636
TI - Cancer screening via infrared spectral cytopathology (SCP): results for the upper
respiratory and digestive tracts.
AB - Instrumental advances in infrared micro-spectroscopy have made possible the
observation of individual human cells and even subcellular structures. The
observed spectra represent a snapshot of the biochemical composition of a cell;
this composition varies subtly but reproducibly with cellular effects such as
progression through the cell cycle, cell maturation and differentiation, and
disease. The aim of this summary is to provide a synopsis of the progress
achieved in infrared spectral cytopathology (SCP) - the combination of infrared
micro-spectroscopy and multivariate methods of analysis - for the detection of
abnormalities in exfoliated human cells of the upper respiratory and digestive
tract, namely the oral and nasopharyngeal cavities, and the esophagus.
PMID- 26421642
TI - Optimizing Pin-Printed and Hydrosilylated Microarray Spot Density on Porous
Silicon Platforms.
AB - Microarrays of spatially isolated chemistries on planar surfaces are powerful
tools. An important factor in microarray technology is the density of chemically
unique spots that can be formed per unit area. In this paper, we use contact pin
printing and evaluate how to decrease contact pin-printed spot diameters on
porous silicon (pSi) platforms. Using hydrosilylation chemistry to covalently
attach chemistries to the pSi surface, the variables studied included pSi
porosity and surface polarity, active agent viscosity, and pin diameter. The spot
characteristics were assessed by Fourier transform infrared spectroscopy (FT-IR)
microscopy and X-ray photoelectron spectroscopy (XPS). Spot size decreased as pSi
porosity increased in accordance with molecular kinetic theory and Darcy's law of
imbibition. Increasing active agent viscosity and pin diameter (volume of printed
agent) led to larger spot diameters in accordance with molecular kinetic theory
and Darcy's law. Oxidizing the pSi with H2O2 increased the surface polarity but
had no detectable impact on the spot size. This is consistent with formation of
an oxide layer atop an unoxidized pSi sublayer.
PMID- 26421634
TI - Association Between Placebo-Activated Neural Systems and Antidepressant
Responses: Neurochemistry of Placebo Effects in Major Depression.
AB - IMPORTANCE: High placebo responses have been observed across a wide range of
pathologies, severely impacting drug development. OBJECTIVE: To examine
neurochemical mechanisms underlying the formation of placebo effects in patients
with major depressive disorder (MDD). DESIGN, SETTING, AND PARTICIPANTS: In this
study involving 2 placebo lead-in phases followed by an open antidepressant
administration, we performed a single-blinded 2-week crossover randomized
clinical trial of 2 identical oral placebos (described as having either active or
inactive fast-acting antidepressant-like effects) followed by a 10-week open
label treatment with a selective serotonin reuptake inhibitor or, in some cases,
another agent as clinically indicated. The volunteers (35 medication-free
patients with MDD at a university health system) were studied with positron
emission tomography and the u-opioid receptor-selective radiotracer
[11C]carfentanil after each 1-week inactive and active oral placebo treatment. In
addition, 1 mL of isotonic saline was administered intravenously within sight of
the volunteer during positron emission tomographic scanning every 4 minutes over
20 minutes only after the 1-week active placebo treatment, with instructions that
the compound may be associated with the activation of brain systems involved in
mood improvement. This challenge stimulus was used to test the individual
capacity to acutely activate endogenous opioid neurotransmision under
expectations of antidepressant effect. MAIN OUTCOMES AND MEASURES: Changes in
depressive symptoms in response to active placebo and antidepressant. Baseline
and activation measures of u-opioid receptor binding. RESULTS: Higher baseline u
opioid receptor binding in the nucleus accumbens was associated with better
response to antidepressant treatment (r = 0.48; P = .02). Reductions in
depressive symptoms after 1 week of active placebo treatment, compared with the
inactive, were associated with increased placebo-induced u-opioid
neurotransmission in a network of regions implicated in emotion, stress
regulation, and the pathophysiology of MDD, namely, the subgenual anterior
cingulate cortex, nucleus accumbens, midline thalamus, and amygdala (nucleus
accumbens: r = 0.6; P < .001). Placebo-induced endogenous opioid release in these
regions was associated with better antidepressant treatment response, predicting
43% of the variance in symptom improvement at the end of the antidepressant
trial. CONCLUSIONS AND RELEVANCE: These data demonstrate that placebo-induced
activation of the u-opioid system is implicated in the formation of placebo
antidepressant effects in patients with MDD and also participate in
antidepressant responses, conferring illness resiliency, during open
administration. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT02178696.
PMID- 26421643
TI - Catalytic Asymmetric Synthesis of Tertiary Alcohols and Oxetenes Bearing a
Difluoromethyl Group.
AB - The catalytic asymmetric ene reaction with difluoropyruvate as an electrophile in
the presence of a dicationic palladium complex is shown. This is the reliable and
practical catalytic asymmetric synthesis for various alpha-CF2H tertiary alcohols
in high yields and enantioselectivities. The reaction with isobutene can be
catalyzed efficiently under solvent-free conditions with low catalyst loading (up
to S/C 2000). Furthermore, difluoropyruvate is applicable to the [2 + 2]
cycloaddition reaction in high yields and enantioselectivities.
PMID- 26421644
TI - Does metoclopramide exposure alter endometrial receptivity and decrease pregnancy
rates?
AB - OBJECTIVE: The aim of this study was to investigate the effect of metoclopramide
on endometrial receptivity with an immunohistochemical investigation of integrin
beta3 expression in pregnant rats. MATERIALS AND METHODS: In the present study,
the pregnant mice administrated by different doses of metoclopramide were used to
explore the effect of metoclopramide on embryo implantation, especially on the
endometrial receptivity. RESULTS: The statistical results showed that the number
of implanted embryos was gradually declining along the increasing dose of
metoclopramide. When the administrated dose of metoclopramide was 3 mg/kg per
day, great changes were observed in the exposed uterine morphology and down
regulated integrin beta3 were also found in high dose metoclopramide-exposed
mice. CONCLUSION: Metoclopramide exposure, especially in high doses may alter
endometrial receptivity by effecting integrin expression on decidual tissue which
can decrease pregnancy rates. This drug should only be recommended for use during
pregnancy when benefit outweighs the risk.
PMID- 26421645
TI - Electronic levels in silicon MaWCE nanowires: evidence of a limited diffusion of
Ag.
AB - Deep level transient spectroscopy (DLTS) was performed on lowly n-doped silicon
nanowires grown by metal-assisted wet chemical etching (MaWCE) with silver as the
catalyst in order to investigate the energetic scheme inside the bandgap. To
observe the possible diffusion of atoms into the bulk, DLTS investigation was
also performed on the samples after removing the nanowires. Two of the four
energy levels observed in the nanowires were also detected inside the substrate.
Based on these results and on literature data about deep levels in bulk silicon,
some hypotheses are advanced regarding the identification of the defects
responsible for the energy levels revealed.
PMID- 26421646
TI - Financial Exploitation of Older Women: A Case Analysis Using the Struggle for
Recognition Theory.
AB - This article aims to make a theoretical contribution to the field of mistreatment
of older adults by introducing Honneth's Struggle for Recognition theory in order
to document financial mistreatment of older women. Through a case analysis of an
older woman financially exploited by her son, considering self-agency and
structure, it shows how financial mistreatment disrespects the three components
of Honneth's theory, primary relationships, legal relations, and community of
value. Personal integrity, social integrity, and honor and dignity are threatened
by mistreatment. This case analysis opens for further theoretical exploration of
the Struggle for Recognition theory in the understanding of mistreatment of older
adults.
PMID- 26421647
TI - Partner Type, Sexual Double Standard Endorsement, and Ambivalence Predict
Abdication and Unprotected Sex Intentions in a Community Sample of Young Women.
AB - In-the-moment ambivalence about having sex may influence sexual decisions but has
rarely been examined. We investigated how ambivalence about sex might be related
to intentions to abdicate sexual decisions to a male partner and to engage in
unprotected sex in a community sample of young women. Predictors of abdication
and unprotected sex intentions included partner type (new casual versus previous
relationship), sexual double standard (SDS) endorsement, and two types of
ambivalence. After completing a SDS endorsement measure, women (N = 360)
projected themselves into a hypothetical sexual situation and completed dependent
measures. In the new casual partner condition, SDS endorsement indirectly
negatively predicted unprotected sex intentions through its associations with
ambivalence and abdication. In both partner conditions SDS endorsement positively
predicted abdication, which then positively predicted unprotected sex intentions.
Ambivalence indirectly predicted unprotected sex intentions through its negative
association with abdication intentions. Results suggest the importance of
ambivalence for sexual decisions and the complexity of understanding the sexual
decision making processes for women who endorse the SDS.
PMID- 26421648
TI - Comment on "Using Satellite-Based Spatiotemporal Resolved Air Temperature
Exposure to Study the Association between Ambient Air Temperature and Birth
Outcomes in Massachusetts".
PMID- 26421651
TI - Distant peer-tutoring for developing countries.
PMID- 26421650
TI - The hydatidiform mole.
AB - The hydatidiform mole (HM) is a placental pathology of androgenetic origin.
Placental villi have an abnormal hyperproliferation event and hydropic
degeneration. Three situations can be envisaged at its origin: 1. The
destruction/expulsion of the female pronucleus at the time of fertilization by 1
or 2 spermatozoa with the former being followed by an endoreplication of the male
pronucleus leading to a complete hydatidiform mole (CHM) 2. A triploid zygote
(fertilization by 2 spermatozoa) leading to a partial hydatidiform mole (PHM) but
can also lead to haploid and diploid clones. The diploid clone may produce a
normal fetus while the haploid clone after endoreplication generates a CHM 3. A
nutritional defect during the differentiation of the oocytes or the deterioration
of the limited oxygen pressure during the first trimester of gestation may lead
to the formation of a HM. In countries with poor medical health care system,
moles (mainly the CHM) can become invasive or, in rare cases, lead to gestational
choriocarcinomas.
PMID- 26421652
TI - Obesogen Holdover: Prenatal Exposure Predicts Cardiometabolic Risk Factors in
Childhood.
PMID- 26421654
TI - Biomechanical assessment of the stabilization capacity of monolithic spinal rods
with different flexural stiffness and anchoring arrangement.
AB - BACKGROUND: Spinal disorders can be treated by several means including fusion
surgery. Rigid posterior instrumentations are used to obtain the stability needed
for fusion. However, the abrupt stiffness variation between the stabilized and
intact segments leads to proximal junctional kyphosis. The concept of spinal rods
with variable flexural stiffness is proposed to create a more gradual transition
at the end of the instrumentation. METHOD: Biomechanical tests were conducted on
porcine spine segments (L1-L6) to assess the stabilization capacity of spinal
rods with different flexural stiffness. Dual-rod fusion constructs containing
three kinds of rods (Ti, Ti-Ni superelastic, and Ti-Ni half stiff-half
superelastic) were implanted using two anchor arrangements: pedicle screws at all
levels or pedicle screws at all levels except for upper instrumented vertebra in
which case pedicle screws were replaced with transverse process hooks. Specimens
were loaded in forward flexion, extension, and lateral bending before and after
implantation of the fusion constructs. The effects of different rods on specimen
stiffness, vertebra mobility, intradiscal pressures, and anchor forces were
evaluated. FINDING: The differences in rod properties had a moderate impact on
the biomechanics of the instrumented spine when only pedicle screws were used.
However, this effect was amplified when transverse process hooks were used as
proximal anchors. INTERPRETATION: Combining transverse hooks and softer (Ti-Ni
superelastic and Ti-Ni half stiff-half superelastic) rods provided more motion at
the upper instrumented level and applied less force on the anchors, potentially
improving the load sharing capacity of the instrumentation.
PMID- 26421653
TI - Self-Propelled Micro-/Nanomotors Based on Controlled Assembled Architectures.
AB - Synthetic micro-/nanomotors (MNMs) are capable of performing self-propelled
motion in fluids through harvesting different types of energies into mechanical
movement, with potential applications in biomedicine and other fields. To address
the challenges in these applications, a promising strategy that combines
controlled assembly (bottom-up approaches) with top-down approaches for
engineering autonomous, multifunctionalized MNMs is under investigation,
beginning in 2012. These MNMs, derived from layer-by-layer assembly or molecular
self-assembly, display the advantages of: i) mass production, ii) response to the
external stimuli, and iii) access to multifunctionality, biocompatibility, and
biodegradability. The advance on how to integrate diverse functional components
into different architectures based on controlled assemblies, to realize
controlled fabrication, motion control (including the movement speed, direction,
and state), and biomedical applications of MNMs, directed by the concept of
nanoarchitectonics, are highlighted here. The remaining challenges and future
research directions are also discussed.
PMID- 26421657
TI - Study of Reciprocal Effects between Mandatory Pollutant Emissions Reduction
Policy and Structural Change within the Manufacturing Sector in a Chinese Coastal
Area.
AB - We develop a multicriteria decision-making model coupled with scenario analysis
to quantitatively elucidate the reciprocal effect between a mandatory pollutant
emissions reduction policy and industrial structure change within the
manufacturing sector on the basis of an in-depth study of a well-developed
coastal area in East China, Ningbo City, toward 2020. First, 18 two-digit level
industries (TDLIs) in the manufacturing sector are screened out due to intensive
emissions of the four pollutants (COD, NH3-N, SO2, and NOx). Second, a model is
established to identify the optimal solution for the industrial structure
adjustment of the 18 TDLIs under two scenarios, the "business-as-usual" scenario
and the "industrial structure adjustment" scenario. Both scenarios are expanded
into three subscenarios. Quantitative constraint conditions and two criteria are
formulated to screen out the optimal solutions. We propose a coefficient of
industrial structure adjustment, Ki, which could clearly reflect the policy
preference in terms of industrial development and reallocate the quota of the
four-pollutant emission among the 18 TDLIs with regards to the different
expectations of economy development in 2020. The model will help local
authorities make tailored policies to reduce pollution emissions effectively
through industrial structure change by delicately allocating the pollutant
emission quota and setting reasonable targets of emission intensity reduction
among TDLIs.
PMID- 26421658
TI - Temporal and Regional Expression of Glucose-Dependent Insulinotropic Peptide and
Its Receptor in Spinal Cord Injured Rats.
AB - Spinal cord injury (SCI) results in loss of movement, sensibility, and autonomic
control at the level of the lesion and at lower parts of the body. Several
experimental strategies have been used in attempts to increase endogenous
mechanisms of neuroprotection, neuroplasticity, and repair, but with limited
success. It is known that glucose-dependent insulinotropic peptide (GIP) and its
receptor (GIPR) can enhance synaptic plasticity, neurogenesis, and axonal
outgrowth. However, their role in the injury has never been studied. The aim of
this study was to evaluate the changes in expression levels of both GIP and GIPR
in acute and chronic phases of SCI in rats. Following SCI (2 to 24 h after
damage), the rat spinal cord showed a lesion in which the epicenter had a cavity
with hemorrhage and necrosis. Furthermore, the lesion cavity also showed
ballooned cells 14 and 28 days after injury. We found that SCI induced increases
in GIPR expression in areas neighboring the site of injury at 6 h and 28 days
after the injury. Moreover, higher GIP expression was observed in these regions
on day 28. Neuronal projections from the injury epicenter showed an increase in
GIP immunoreactivity 24 h and 14 and 28 days after SCI. Interestingly, GIP was
also found in progenitor cells at the spinal cord canal 24 h after injury,
whereas both GIP and GIPR were present in progenitor cells at the injury
epicenter 14 days after in SCI animals. These results suggest that GIP and its
receptor might be implicated with neurogenesis and the repair process after SCI.
PMID- 26421659
TI - Estimation of surface-level PM concentration from satellite observation taking
into account the aerosol vertical profiles and hygroscopicity.
AB - Surface-level PM10 distribution was estimated from the satellite aerosol optical
depth (AOD) products, taking the account of vertical profiles and hygroscopicity
of aerosols over Jeju, Korea during March 2008 and October 2009. In this study,
MODIS AOD data from the Terra and Aqua satellites were corrected with aerosol
extinction profiles and relative humidity data. PBLH (Planetary Boundary Layer
Height) was determined from MPLNET lidar-derived aerosol extinction coefficient
profiles. Through statistical analysis, better agreement in correlation (R =
0.82) between the hourly PM10 concentration and hourly average Sunphotometer AOD
was the obtained when vertical fraction method (VFM) considering Haze Layer
Height (HLH) and hygroscopic growth factor f(RH) was used. The validity of the
derived relationship between satellite AOD and surface PM10 concentration clearly
demonstrates that satellite AOD data can be utilized for remote sensing of
spatial distribution of regional PM10 concentration.
PMID- 26421660
TI - Regenerative Electrode Interfaces for Neural Prostheses.
AB - Neural prostheses are electrode arrays implanted in the nervous system that
record or stimulate electrical activity in neurons. Rapid growth in the use of
neural prostheses in research and clinical applications has occurred in recent
years, but instability and poor patency in the tissue-electrode interface
undermines the longevity and performance of these devices. The application of
tissue engineering strategies to the device interface is a promising approach to
improve connectivity and communication between implanted electrodes and local
neurons, and several research groups have developed new and innovative
modifications to neural prostheses with the goal of seamless device-tissue
integration. These approaches can be broadly categorized based on the strategy
used to maintain and regenerate neurons at the device interface: (1) redesign of
the prosthesis architecture to include finer-scale geometries and/or provide
topographical cues to guide regenerating neural outgrowth, (2) incorporation of
material coatings and bioactive molecules on the prosthesis to improve neuronal
growth, viability, and adhesion, and (3) inclusion of cellular grafts to
replenish the local neuron population or provide a target site for reinnervation
(biohybrid devices). In addition to stabilizing the contact between neurons and
electrodes, the potential to selectively interface specific subpopulations of
neurons with individual electrode sites is a key advantage of regenerative
interfaces. In this study, we review the development of regenerative interfaces
for applications in both the peripheral and central nervous system. Current and
future development of regenerative interfaces has the potential to improve the
stability and selectivity of neural prostheses, improving the patency and
resolution of information transfer between neurons and implanted electrodes.
PMID- 26421661
TI - "Mind the Gap": Raman Evidence for Rapid Inactivation of CTX-M-9 beta-Lactamase
Using Mechanism-Based Inhibitors that Bridge the Active Site.
AB - CTX-M beta-lactamases are one of the fastest growing extended-spectrum beta
lactamase (ESBL) families found in Escherichia coli rendering this organism
extremely difficult to treat with beta-lactam antibiotics. Although they are
grouped in class A beta-lactamases, the CTX-M family possesses low sequence
identity with other enzymes. In addition, they have high hydrolytic activity
against oxyimino-cephalosporins, despite having smaller active sites compared to
other ESBLs in class A. Similar to most class A enzymes, most of the CTX-M beta
lactamases can be inhibited by the clinical inhibitors (clavulanic acid,
sulbactam, and tazobactam), but the prevalence of inhibitor resistance is an
emerging clinical threat. Thus, the mechanistic details of inhibition pathways
are needed for new inhibitor development. Here, we use Raman microscopy to study
the CTX-M-9 inactivation reaction with the three commercially available
inhibitors and compare these findings to the analysis of the S130G variant.
Characterization of the reactions in CTX-M-9 single crystals and solution show
the formation of a unique cross-linked species, probably involving Ser70 and
Ser130, with subsequent hydrolysis leading to an acrylate species linked to
Ser130. In solution, a major population of this species is seen at 25 ms after
mixing. Support for this finding comes from the CTX-M-9 S130G variant that reacts
with clavulanic acid, sulbactam, and tazobactam in solution, but lacks the
characteristic spectroscopic signature for the Ser130-linked species.
Understanding the mechanism of inactivation of this clinically important ESBL
type class A lactamase permits us to approach the challenge of inhibitor
resistance using knowledge of the bridging species in the inactivation pathway.
PMID- 26421662
TI - Dipstick albuminuria and acute kidney injury recovery in critically ill septic
patients.
AB - AIM: Acute kidney injury (AKI) is a frequent complication of sepsis, a pro
inflammatory state that alters tubular handling of filtered albumin. We
hypothesized that dipstick albuminuria (DA) is associated with a lower rate of
AKI recovery in septic patients. METHODS: This was a single-centre, retrospective
cohort study of adults with sepsis-associated AKI in an urban academic intensive
care unit (ICU). Patients with unknown baseline serum creatinine (SCr), absent
urinalysis, and those with estimated glomerular filtration rate (eGFR) <15 mL/min
per 1.73m(2) or receiving chronic renal replacement therapy (RRT) were excluded.
The independent variable was DA (negative or trace, 30 mg/dL, and >=100 mg/dL)
within the first 72 h of ICU stay. The outcome variable was AKI recovery at 30
days following hospital discharge, defined as the last SCr returning to a level
less than 1.5 times the baseline SCr level and independence of RRT. RESULTS: A
total of 988 patients were included in the study. The median length of
hospitalization was 11 days. The patients with higher degree of DA had worse
critical illness scores. After adjustment for several confounders, DA >=30 mg/dL
was independently associated with "no AKI recovery" at 30 days post-discharge
(adjusted OR 1.40, 95% CI, 1.01-1.95 for DA =30 mg/dL and 1.67, 1.15-2.42 for DA
>=100 mg/dL, P = 0.02). Other independent predictors of "no AKI recovery" were
cumulative fluid balance, Sequential Organ Failure Assessment (SOFA) score,
exposure to diuretics, and the need for mechanical ventilation. CONCLUSION:
Dipstick albuminuria >=30 mg/dL is independently associated with lower rate of
AKI recovery at 30 days post-discharge. Our findings emphasize the potential
utility of a simple routine test of DA in the risk-stratification of AKI recovery
in ICU septic patients.
PMID- 26421663
TI - Estimated Lifetime Medical and Work-Loss Costs of Emergency Department-Treated
Nonfatal Injuries--United States, 2013.
AB - A large number of nonfatal injuries are treated in U.S. emergency departments
(EDs) every year. CDC's National Center for Health Statistics estimates that
approximately 29% of all ED visits in 2010 were for injuries. To assess the
economic impact of ED-treated injuries, CDC examined injury data from the
National Electronic Injury Surveillance System--All Injury Program (NEISS-AIP)
for 2013, as well as injury-related lifetime medical and work-loss costs from the
Web-Based Injury Statistics Query and Reporting System (WISQARS). NEISS-AIP
collects data from a nationally representative sample of EDs, using specific
guidelines for recording the primary diagnosis and mechanism of injury. Number of
injuries, crude- and age-specific injury rates, and total lifetime work-loss
costs and medical costs were calculated for ED-treated injuries, stratified by
sex, age groups, and intent and mechanism of injury. ED-treated injuries were
further classified as those that were subsequently hospitalized or treated and
released. The rate of hospitalized injuries was 950.8 per 100,000, and the rate
of treated and released injuries was 8,549.8 per 100,000. Combined medical and
work-loss costs for all ED-treated injuries (both hospitalized and treated and
released) were $456.9 billion, or approximately 68% of the total costs of $671
billion associated with all fatal and ED-treated injuries. The substantial
economic burden associated with nonfatal injuries underscores the need for
effective prevention strategies.
PMID- 26421664
TI - The c.63A>G polymorphism in the NKX2.5 gene is associated with thyroid hypoplasia
in children with thyroid dysgenesis.
AB - OBJECTIVE: To search for genetic alteration in NKX2.5 gene in patients presenting
both congenital heart disease (CHD) and TD. SUBJECTS AND METHODS: Individual
phenotypes were carefully analyzed in 86 children with thyroid dysgenesis (TD)
using thyroid function tests, scintigraphy, ultrasound and echocardiography. DNA
was extracted and NKX2.5 gene coding region was amplified by polymerase chain
reaction (PCR) and sequenced. RESULTS: CHD were found in 8.1% of patients with
TD. The mutation screening revealed two known polymorphisms in patients with
isolated TD or TD associated with CHD. None of them are predicted to result in
codon change in conserved domain. The c.63A>G polymorphism was detected in 54/86
patients (49 with isolated TD and 5 with TD combined with CHD). There was a
significant association of c.63A>G polymorphism with hypoplasia (p < 0.036). The
c.541G>A polymorphism was observed in only one patient with isolated thyroid
hypoplasia. CONCLUSION: NKX2.5 mutations were not found. The c.63A>G polymorphism
might be associated with thyroid hypoplasia.
PMID- 26421665
TI - Low iodine diet does not improve the efficacy of radioiodine for the treatment of
Graves' disease.
AB - OBJECTIVE: Consuming a low-iodine diet (LID) is a widely accepted practice before
administering radioiodine (131I) to evaluate and to treat thyroid disease.
Although this procedure is well established for the management of patients with
differentiated thyroid cancer, its use in patients with benign disease is
unclear. So, we aimed to evaluate the influence of a LID on the outcome in
patients with Graves' disease (GD) treated with 131I. SUBJECTS AND METHODS: We
evaluated 67 patients with GD who were divided into 2 groups: one group (n = 31)
consumed a LID for 1-2 weeks, and the second group (n = 36) was instructed to
maintain a regular diet (RD). RESULTS: The LID group experienced a 23% decrease
in urinary iodine after 1 week on the diet and a significant 42% decrease after 2
weeks on the diet. The majority (53%) of the patients in the LID group had
urinary iodine levels that were consistent with deficient iodine intake. However,
there was no difference in the rate of hyperthyroidism's cure between the LID and
the RD groups 6 months after 131I therapy. Furthermore, the therapeutic efficacy
did not differ in patients with varying degrees of sufficient iodine intake
(corresponding urinary iodine levels: < 10 MUg/dL is deficient; 10-29.9 MUg/dL is
sufficient; and > 30 MUg/dL is excessive). CONCLUSION: In the present study, we
demonstrated that although a LID decreased urinary iodine levels, those levels
corresponding with sufficient or a mild excess in iodine intake did not
compromise the therapeutic efficacy of 131I for the treatment of GD.
PMID- 26421666
TI - Effects of thyroid hormone replacement on glycated hemoglobin levels in non
diabetic subjects with overt hypothyroidism.
AB - OBJECTIVE: Glycated hemoglobin (HbA1c) may not accurately reflect the level of
glycemia in conditions of altered erythrocyte turnover. Hypothyroidism is one
condition associated with sluggish erythropoesis. To assess changes in HbA1c,
independent of changes in plasma glucose after initiation of thyroxine
replacement in patients with overt hypothyroidism. MATERIALS AND METHODS: In this
prospective longitudinal study carried out in a tertiary care centre, adult non
diabetic patients with overt hypothyroidism recruited between March 2012 to
August 2013 were rendered euthyroid on thyroxine. They underwent testing for
hemoglobin, HbA1c, reticulocyte count, thyroxine, thyrotropin and a standard oral
glucose tolerance test, both before and at 3 months after restoration to the
euthyroid state. Main outcome assessed was the change in HbA1c independent of the
change in glucose parameters. RESULTS: Thirty eight patients (35 female and 3
male) aged 37.8 +/- 10.2 years with overt hypothyroidism (thyroxine 12.6 +/- 13.4
ng/mL and thyrotropin -98.1 +/- 63.7 uIU/mL respectively) were recruited. While
HbA1c fell from 5.8 +/- 0.7% to 5.6 +/- 0.5% (p = 0.009) at 3 months following
the correction of hypothyroidism, there were no changes in the fasting and the 2
hr post oral glucose tolerance test glucose (p = 0.67 and 0.56 respectively). The
number of patients with dysglycemia diagnosed by HbA1c (i.e HbA1c >= 5.7%) fell
from 25 (65.78%) to 17 (44.7%) after treatment (p = 0.008). There were 7 (18.4%)
patients with HbA1c >= 6.5% at baseline, but this fell to just 4 (10.5%) (p <
0.001) after 3 months of euthyroidism. CONCLUSION: HbA1c is not a reliable
diagnostic test for diabetes in the presence of hypothyroidism.
PMID- 26421667
TI - Atkins diet program rapidly decreases atherogenic index of plasma in trained
adapted overweight men.
AB - BACKGROUND: The Atkins diet program is a great example of the application of low
carbohydrate diets for obesity, with the intention of weight loss and improvement
in cardiovascular risk (CV risk). A good CV risk predictor is the atherogenic
index of plasma (AIP) calculated as log (TG/HDL [mmol]), which is strongly
affected by serum triglycerides, which in turn is associated with the
carbohydrate intake. This study determined the effect of the initial phase of
Atkins diet program, consisting in 20 g/day of carbohydrate intake with positive
urinary ketones measure, in AIP of 12 adult overweight trained adapted men. The
AIP was calculated before and after intervention. RESULTS: After 14 days, BMI and
triglycerides decreased significantly, while HDL-C increased. No alterations were
described in LDL plasmatic concentration. Prior to the diet, 58.3% of subjects
presented high CV risk and after 14 days of the diet program only 33.3% of
subjects were classified as high CV risk, while more than 66% were low CV risk.
The intervention was effective in 11 of 12 participants. However, in one person
the dietary intervention increased AIP index. CONCLUSION: The initial phase of
Atkins diet program could significantly decrease the AIP in 11 of 12 adult
overweight trained adapted men. Dietary individual responses need to be more
studied.
PMID- 26421669
TI - Anti-thyroid drug-induced lupus: a case report and review of the literature.
AB - We report a case of drug-induced lupus (DIL) on a Chinese woman caused by
methimazole (MMI). This report discusses DIL associated with MMI and briefly
reviewed the literature concerning to anti-thyroid DIL.
PMID- 26421668
TI - Evaluation of central precocious puberty treatment with GnRH analogue at the
Triangulo Mineiro Federal University (UFTM).
AB - OBJECTIVE: To report our experience of treating central precocious puberty (CPP)
with a GnRH analogue with respect to the final heights (FH) attained in patients
who completed treatment. SUBJECTS AND METHODS: Among 105 records of children
diagnosed with precocious puberty, 62 cases (54 girls and 8 boys), who were
treated with leuprolide acetate/3.75 mg/monthly, were selected, and divided into
4 groups: group 1 (G1), 25 girls who attained FH; group 2 (G2), 18 girls who
completed treatment but did not reach FH; group 3 (G3), 11 girls still under
treatment; and group 4 (G4), 8 boys, 5 of which attained FH. Treatment was
concluded at a bone age of 12 years, and follow-up continued until FH was
achieved. RESULTS: In both G1 and G2 groups, height standard deviation score
(SDS), weight-SDS and percentile of body mass index (PBMI) did not show
intra/intergroup differences at the beginning and at interruption of treatment,
but when added, G1+G2, height-SDS and weight-SDS differed significantly (p =
0.002 and 0.0001, respectively). In G1, 19 of 25 cases attained TH, and average
height gain was 16.7 cm (7.7- 27.1); there was significant difference between FH
and prediction of FH at the start (PFH at start) (p = 0.0001), as well as between
PFH at interruption vs TH and vs FH (p = 0.007) with FH higher than TH (p =
0.004). Significant correlation was identified between FH and height gain after
treatment. CONCLUSION: As shown by some studies, GnRH analogue treatment was
effective in children with CPP reaching FH near the genetic target.
PMID- 26421670
TI - Effect of the consumption on buriti oil on the metabolism of rats induced by iron
overload.
AB - OBJECTIVES: To compare the effect of the consumption of buriti oil and soybean
oil on the metabolism of rats under stress induced by iron overload. MATERIALS
AND METHODS: A total of 28 rats were randomized into control groups who consumed
diet added of soybean (CS) or buriti oil (CB) and gavage with saline and two
experimental groups who consumed diet added of soybean (ES) or buriti oil (EB)
and daily gavage with iron II sulfate as stress inducer. The fatty acid profile
of diets was analyzed. Body weight and diet consumption were evaluated every two
days. The lipid profile and liver weight of animals were evaluated at the end of
the experiment. RESULTS: Diet added of soybean oil showed higher percentage of
polyunsaturated fatty acids (45.6%) and diet with buriti oil was rich in
monounsaturated fatty acids (66.9%). There were no differences in food intake,
total cholesterol, HDL-cholesterol and LDL-cholesterol among groups (p > 0.05).
However, animals fed with diet supplemented with buriti oil showed intermediate
triglyceride levels (CB: 65 mg/dL; EB: 68.7 mg/dL) compared to ES group (102.5
mg/dL). The liver of rats from the CS group had higher weight (2.06 +/- 0.2 g)
compared to the CB group (1.56 +/- 0.1 g). CONCLUSION: Buriti oil consumption was
able to minimize some changes related to iron overload.
PMID- 26421671
TI - Painless thyroiditis associated to thyroid carcinoma: role of initial
ultrasonography evaluation.
AB - Even though it is a rare event, most associations of thyroid carcinoma with
subacute thyroiditis described in the literature are related to its granulomatous
form (Quervain's thyroiditis). We present a patient with subacute lymphocytic
thyroiditis (painless thyroiditis) and papillary thyroid cancer that was first
suspected in an initial ultrasound evaluation. A 30-year old female patient who
was referred to the emergency room due to hyperthyroidism symptoms was diagnosed
with painless thyroiditis established by physical examination and laboratory
findings. With the presence of a palpable painless thyroid nodule an ultrasound
was prescribed and the images revealed a suspicious thyroid nodule,
microcalcification focus in the heterogeneous thyroid parenquima and cervical
lymphadenopathy. Fine needle aspiration biopsy was taken from this nodule;
cytology was assessed for compatibility with papillary thyroid carcinoma.
Postsurgical pathology evaluation showed a multicentric papillary carcinoma and
lymphocytic infiltration. Subacute thyroiditis, regardless of type, may produce
transitory ultrasound changes that obscure the coexistence of papillary
carcinoma. Due to this, initial thyroid ultrasound evaluation should be delayed
until clinical recovery. We recommended a thyroid ultrasound exam for initial
evaluation of painless thyroiditis, particularly in patients with palpable
thyroid nodule. Further cytological examination is recommended in cases
presenting with suspect thyroid nodule and/or non-nodular hypoechoic (> 1 cm) or
heterogeneous areas with microcalcification focus.
PMID- 26421672
TI - Six-week anaerobic training improves proteolytic profile of diabetic rats.
AB - OBJECTIVE: To evaluate the effect of six-week anaerobic training on the mRNA
expression of genes related to proteolysis Ubb (Ubiquitin), E2-14kDa, Trim63
(MuRF1 protein) and Nfkb1 in the skeletal muscle of diabetic rats. MATERIALS AND
METHODS: Four groups were established: DE (DiabetesExercised), DS (Diabetes
Sedentary), CE (Control Exercised) and CS (Control Sedentary). The training
consisted of 3 sets of 12 jumps in the liquid mean with load equivalent to 50% of
BW for 6 weeks. Euthanasia occurred under ip anesthesia, and blood, adipose
tissue and skeletal muscles were collected. Gene expression was quantified by RT
PCR in the gastrocnemius muscle. ANOVA one-way was used for comparison among
groups, with post-hoc (Tukey) when necessary, considering p < 0.05. RESULTS: We
observed reduction in the body weight and adipose tissue in the diabetic groups.
The muscle mass was reduced in DS, which could be reversed by training (DE).
Although DS and DE have presented similar body weight, the training protocol in
DE promoted reduction in the adipose tissue, and increase of muscle mass.
Anaerobic training was efficient to reduce glycaemia only in the diabetic animals
until 6 hours after the end of training. The Trim63 gene expression was increased
in DS; decreased Ubb gene level was observed in trained rats (CE and DE) compared
to sedentary (CS and DS), and DE presented the lowest level of E2-14kDa gene
expression. CONCLUSION: Six-week anaerobic training promoted muscle mass gain,
improved glycemic control, and exerted inhibitory effect on the proteolysis of
gastrocnemius muscle of diabetic rats.
PMID- 26421673
TI - Genetic and environmental influence on thyroid gland volume and thickness of
thyroid isthmus: a twin study.
AB - OBJECTIVES: Decreased thyroid volume has been related to increased prevalence of
thyroid cancer. SUBJECTS AND METHODS: One hundred and fourteen Hungarian adult
twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders
underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at
the thickest portion of the gland in the midline using electronic calipers at the
time of scanning. Volume of the thyroid lobe was computed according to the
following formula: thyroid height*width*depth*correction factor (0.63). RESULTS:
Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness
of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither
left nor right thyroid volume showed additive genetic effects, but shared
environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%),
respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were
not substantially impacted by the correction of covariates of body mass index and
smoking. Unshared environmental effects showed a moderate influence on dependent
parameters (24-50%). CONCLUSIONS: Our analysis support that familial factors are
important for thyroid measures in a general twin population. A larger sample size
is needed to show whether this is because of common environmental (e.g.
intrauterine effects, regional nutrition habits, iodine supply) or genetic
effects.
PMID- 26421674
TI - Association between atypical parathyroid adenoma and neurofibromatosis.
AB - Primary hyperparathyroidism is a disease characterized by excessive production of
parathyroid hormone (PTH), which is due to a parathyroid adenoma in 85% of cases.
An atypical parathyroid adenoma, with some histopathological features of
parathyroid carcinoma, may be found in some of the cases, although it may not
fulfill all the criteria for this diagnosis. Neurofibromatosis type 1 (NF1) is an
autosomal dominant systemic disease that may be associated with
hyperparathyroidism. We report here the rare combination of a patient with NF1
and clinical manifestations of hyperparathyroidism due to an atypical parathyroid
adenoma.
PMID- 26421675
TI - The Clinical Practice of Assessing Cognitive Function in Adults Receiving
Electroconvulsive Therapy: Whom Are We Missing?
AB - BACKGROUND: Cognition can be affected by electroconvulsive therapy (ECT). Good
clinical practice includes neuropsychological assessment, although this is seldom
a part of routine clinical practice. It looks like a substantial part of patients
fail to complete cognitive assessments. This constitutes a problem in the
generalizability of published clinical research on cognitive side effects. Most
studies of ECT-related cognitive adverse effects do not discuss this important
issue of so-called cognitive test nonparticipants. Recent findings suggest that
cognitive test nonparticipants are more severely ill, and probably more
vulnerable to cognitive side effects. OBJECTIVES: To examine the feasibility of a
neuropsychological test battery in daily clinical practice, in an adult
population referred for ECT. METHODS: We reviewed the clinical records of 84
patients referred for ECT. Demographic and clinical characteristics of those
patients who were able to complete our routine cognitive testing at baseline are
compared with those who could not complete the assessment. RESULTS: From 84 ECT
patients, 60 (71%) completed a pre-ECT cognitive assessment, whereas 24 (29%) did
not. Patients with a unipolar depression, with psychotic symptoms, who started
their treatment with a bitemporal electrode placement were more likely to be test
noncompleters than test completers. CONCLUSIONS: Patients with a unipolar
depression, with psychotic features, who are treated with a bitemporal electrode
placement, have a higher likelihood of not completing a pre-ECT cognitive
assessment. These patients probably represent a subgroup more vulnerable to
cognitive side effects.
PMID- 26421676
TI - Current Resources for Evidence-Based Practice, September/October 2015.
PMID- 26421677
TI - Buprenorphine for neuropathic pain in adults.
AB - BACKGROUND: Opioid drugs, including buprenorphine, are commonly used to treat
neuropathic pain, and are considered effective by some professionals. Most
reviews have examined all opioids together. This review sought evidence
specifically for buprenorphine, at any dose, and by any route of administration.
Other opioids are considered in separate reviews. OBJECTIVES: To assess the
analgesic efficacy of buprenorphine for chronic neuropathic pain in adults, and
the adverse events associated with its use in clinical trials. SEARCH METHODS: We
searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
and EMBASE from inception to 11 June 2015, together with reference lists of
retrieved papers and reviews, and two online study registries. SELECTION
CRITERIA: We included randomised, double-blind studies of two weeks' duration or
longer, comparing any oral dose or formulation of buprenorphine with placebo or
another active treatment in chronic neuropathic pain. DATA COLLECTION AND
ANALYSIS: Two review authors independently searched for studies, extracted
efficacy and adverse event data, and examined issues of study quality. We did not
carry out any pooled analyses. MAIN RESULTS: Searches identified 10 published
studies, and one study with results in ClinicalTrials.gov. None of these 11
studies satisfied our inclusion criteria, and so we included no studies in the
review. AUTHORS' CONCLUSIONS: There was insufficient evidence to support or
refute the suggestion that buprenorphine has any efficacy in any neuropathic pain
condition.
PMID- 26421678
TI - Food Ingredients as Anti-Obesity Agents.
AB - Brown adipose tissue (BAT) is a site of adaptive non-shivering thermogenesis
after cold exposure, and is involved in the regulation of energy expenditure and
body fatness. BAT can be activated and recruited by not only cold exposure but
also by various food ingredients including capsaicin in chili pepper and
catechins in green tea, which would be easily and safely applicable to our daily
life for preventing obesity.
PMID- 26421681
TI - The clinical presentation of acute bacterial meningitis varies with age, sex and
duration of illness.
AB - AIM: This Swedish study reviewed differences in clinical presentation and
laboratory findings of acute bacterial meningitis in children aged one month to
17 years in Vasterbotten County, Sweden. METHODS: A register-based study was
performed for the period 1986 to 2013 using the Vasterbotten County Council's
patient registration and laboratory records at the Department of Laboratory
Medicine at Umea University Hospital. The medical records were reviewed to
extract data and confirm the diagnosis. RESULTS: We found 103 cases of acute
bacterial meningitis, and Haemophilus influenzae was the most common pathogen,
causing 40.8% of all cases, followed by Streptococcus pneumoniae at 30.1% and
Neisseria meningitidis at 9.7%. Significant differences in clinical presentation
and laboratory findings were found. Younger children were more unwell than older
ones and had more diffuse symptoms on admission. In addition, important sex
related differences were found that might explain the higher case fatality rates
for boys than girls. For example, boys tended to have a higher disturbance in the
blood-brain barrier, which is known to be a negative prognostic factor.
CONCLUSION: This study showed that clinical presentation for acute bacterial
meningitis varied with age and sex and, to a lesser extent, on the duration of
the illness.
PMID- 26421679
TI - Ty3 Retrotransposon Hijacks Mating Yeast RNA Processing Bodies to Infect New
Genomes.
AB - Retrotransposition of the budding yeast long terminal repeat retrotransposon Ty3
is activated during mating. In this study, proteins that associate with Ty3 Gag3
capsid protein during virus-like particle (VLP) assembly were identified by mass
spectrometry and screened for roles in mating-stimulated retrotransposition.
Components of RNA processing bodies including DEAD box helicases Dhh1/DDX6 and
Ded1/DDX3, Sm-like protein Lsm1, decapping protein Dcp2, and 5' to 3' exonuclease
Xrn1 were among the proteins identified. These proteins associated with Ty3
proteins and RNA, and were required for formation of Ty3 VLP retrosome assembly
factories and for retrotransposition. Specifically, Dhh1/DDX6 was required for
normal levels of Ty3 genomic RNA, and Lsm1 and Xrn1 were required for association
of Ty3 protein and RNA into retrosomes. This role for components of RNA
processing bodies in promoting VLP assembly and retrotransposition during mating
in a yeast that lacks RNA interference, contrasts with roles proposed for
orthologous components in animal germ cell ribonucleoprotein granules in turnover
and epigenetic suppression of retrotransposon RNAs.
PMID- 26421680
TI - A study of stromal riboflavin absorption in ex vivo porcine corneas using new and
existing delivery protocols for corneal cross-linking.
AB - PURPOSE: To indirectly measure stromal riboflavin penetration using commercially
available riboflavin solutions and new and existing epithelium-off, trans
epithelial and iontophoresis-assisted delivery protocols. METHODS: Forty porcine
eyes were divided into eight groups. Group 1: Ricrolin applied to the de
epithelialised cornea for 30 min; Group 2: epithelium-intact, no treatment;
Groups 3-5: epithelium-intact, 30-min application of Ricrolin TE, Mediocross TE
or ParaCel/Vibex, respectively. Group 6: epithelium-intact, Ricrolin(+)
iontophoresis-assisted delivery for 5 min; Group 7: epithelium-intact,
Ricrolin(+) iontophoresis-assisted delivery for 5 min with a 20-min riboflavin
soak; and Group 8: epithelium-intact, Ricrolin(+) iontophoresis-assisted delivery
for 5 min, 15-min soak and another 5 min of iontophoresis. After a saline wash,
light transmission spectra were obtained from each cornea, before and after
epithelial removal. RESULTS: Corneas in groups 1 and 8 showed a distinct
riboflavin absorption peak between 400 and 520 nm. The optical density of the
corneas in groups 3-7 did not differ significantly from that of the untreated
corneas (group 2). CONCLUSIONS: A modification to the standard iontophoresis
trans-epithelial technique resulted in successful penetration of riboflavin into
the stroma and appears to offer the most promise for epithelium-on cross-linking.
PMID- 26421682
TI - Diagnostic Dilemma in Sequential Branch Retinal Vein and Artery Occlusion.
AB - PURPOSE: To report on an unusual case of a branch retinal vein occlusion followed
by occlusion of the respective branch retinal artery of the same eye 7 years
later, in a young, otherwise healthy man with marginal elevation of
antiphospholipid antibodies. CASE REPORT: On first presentation, a 30-year-old
male patient was diagnosed as having a branch retinal vein occlusion with the
sole risk factor of slightly increased diastolic pressure. On second
presentation, 7 years later, a transient occlusion of the respective branch
retinal artery was diagnosed on the same patient. Extensive ophthalmologic and
general medical evaluations were performed including cardiovascular, coagulation,
and immunology testing. Coagulopathy screening revealed slightly elevated titers
of anticardiolipin IgM and anti-beta 2 glycoprotein-I IgM antibodies, and aspirin
prophylaxis was initiated. CONCLUSIONS: Retinal vascular occlusions are typically
associated with well-defined, classical risk factors in older people. In younger,
otherwise healthy patients, further autoimmune hypercoagulable disorders are
often causal. Our case suggests the contribution of slightly elevated
antiphospholipid IgM antibodies, although this remains to be proven.
PMID- 26421683
TI - Head-Eye Coordination Increases with Age and Varies across Countries.
AB - PURPOSE: Head movements in older people may contribute to their dizziness and
equilibrium problems. Head gain is the ratio of head movement to total movement
(head + eye) when executing a saccade to an eccentric target. Two studies have
investigated the relationship between head gain and age but have provided
conflicting results. METHODS: We report head gain data collected from research
laboratories and optician stores. Our sample sizes are much larger (n = 657 for
laboratory, n = 64,458 for optician stores), permitting more detailed analyses.
RESULTS: The head-eye coefficient, expressed as 100 times the square root of head
gain, was bimodal with one mode of primarily eye movers and one mode of eye-and
head movers. Head-eye coefficient increased with age and was invariant with eye
correction and gender. We also found an effect of nation that seemed associated
with gross domestic product or by latitude (in the northern hemisphere) and log
population density. DISCUSSION: Assuming that head movements and visual
distortions contribute to dizziness and equilibrium problems, our study suggests
that customizing eyewear based on age and country may help in reducing the
prevalence of problems associated with head and/or eye movements.
PMID- 26421685
TI - A Pragmatic Approach to Dry Eye Diagnosis: Evidence into Practice.
AB - Dry eye disease (DED) is a common, multifactorial disease of the tears and
anterior ocular surface. The clinical diagnosis of DED is complex, requiring the
consideration of both patient symptoms and signs, which can be apparently
contradictory. Misdiagnosis can lead to suboptimal clinical management. Studies
of the practice behaviors of optometrists suggest that there is the potential to
improve the translation of research evidence relating to the diagnosis of DED
into primary ophthalmic care. This review describes an evidence-based, pragmatic
approach to the contemporary clinical diagnosis of DED, as a means for guiding
best practice for the care of dry eye patients.
PMID- 26421684
TI - Accommodative Gain in Relation to Perceived Target Clarity.
AB - PURPOSE: The purpose of this study is to determine the relationship between
target clarity and the magnitude of accommodative lag using the metric
accommodative gain (AG). METHODS: Monocular accommodative responses were measured
with Grand Seiko autorefraction using both proximal and minus lens techniques in
139 subjects aged 5 to 35 years. Subjects viewed a 1.5-mm letter at 13 discrete
distances (range, 40 to 3.33 cm) for the proximal technique and fixed at 33 cm
through minus lenses of increasing power for the lens technique. Subjects were
instructed to keep the target clear and report when it blurred. The AG was
calculated (accommodative response/accommodative demand) for the four greatest
consecutive demands perceived clear (termed conditions 1 to 4) and the first
demand perceived blurry (termed condition 5). RESULTS: Multivariate planned
contrast, including age as a predictor, revealed that mean AG was significantly
larger when the target was clear (range, 0.71 to 0.77 for conditions 1 to 4
across techniques) versus blurry (0.59 and 0.68 for condition 5 across
techniques) (p < 0.001 for proximal and p < 0.036 for lens). Age was only a
contributing factor for the proximal technique, with the youngest subjects having
the largest decrease in AG when the target changed from clear to blurry (p =
0.017). CONCLUSIONS: These data suggest that across age and technique, the AG is
relatively constant when the target is perceived clear but drops below
approximately 70%, on average, once the target is perceived as blurry for
subjects aged 5 to 35 years. The AG may be a useful metric to compare
accommodative responses across a range of demands and to identify accommodative
responses that may not be sufficient to perceive a clear target.
PMID- 26421686
TI - Association of IOP with Systemic Factors in a Korean Cohort.
AB - PURPOSE: To assess the relationship of intraocular pressure (IOP) to age, sex,
and other demographic and health characteristics in a Korean cohort. METHODS:
This retrospective cross-sectional study included subjects (n = 155,198) without
glaucoma. All participants underwent health screening at the Kangbuk Samsung
Hospital from August 2012 to July 2013. Anthropometric measurements, systemic
health characteristics, and ocular examination including noncontact tonometry
were performed on all participants. Additionally, sociodemographic and behavioral
questionnaires were obtained. The systemic variables were analyzed by multiple
regression analysis to identify their relationship with IOP. RESULTS: The mean
IOP tended to be highest in subjects in their 50s and lowest in subjects in their
20s and 60s for both Korean men and women. This pattern remained the same after
adjusting for several demographic and health characteristics. The mean IOP for
men was significantly higher than that for women (p < 0.001), but the difference
between sexes decreased with increasing age. In the univariate analysis, almost
all systemic factors showed a positive association with IOP except for high
density lipoprotein cholesterol. By multiple regression analysis, IOP was
positively associated with sex (male), current smoking status, systolic blood
pressure, fasting plasma glucose, body mass index, total cholesterol, and high
density lipoprotein (p <= 0.001). CONCLUSIONS: In a Korean cohort, the mean IOP
was highest in subjects in their 50s. The mean IOP for men was significantly
higher than that for women. Several systemic factors were significantly
correlated with IOP.
PMID- 26421687
TI - The APC I1307K allele conveys a significant increased risk for cancer.
AB - This study is the first attempt to evaluate the association between the APC
I1307K variant and overall cancer risk. It is unique in both its large sample
size and in the reliability of data in the control group. The findings described
in this article have major implications in terms of identifying asymptomatic
individuals who are at increased risk to harbor cancer and therefore targeted to
be enrolled in specific early detection and prevention programs. The prevalence
of the APC I1307K missense mutation among Ashkenazi Jews is ~ 6%. Carriers are at
an increased risk for colorectal neoplasia. In this study, we examined the
association of this variant with non-colorectal cancers. Consecutive 13,013
healthy subjects who underwent screening at the Integrated Cancer Prevention
Center between 2006 and 2014 were enrolled. This population was supplemented with
1,611 cancer patients from the same institution. Demographics, medical history,
and pathological data were recorded. Mortality data were obtained from the
Ministry of Health's registry. The prevalence of APC I1307K in cancer patients
and healthy subjects was compared. The APC I1307K variant was detected in 189
(11.8%) cancer patients compared to 614 (4.7%) healthy subjects, reflecting an
adjusted age and sex odds ratio (OR) of 2.53 (p < 0.0001). History of two or more
cancer types was associated with a positive carrier prevalence (OR = 4.38 p <
0.0001). Males had significantly increased carrier prevalence in lung, urologic,
pancreatic, and skin cancers. The carrier prevalence among females was
significantly higher only in breast and skin cancers. Female carriers developed
cancer at a significantly older age compared to non-carriers (average 62.7 years
vs. 57.8, respectively, p = 0.027), had better survival rates (HR = 0.58, p =
0.022) and overall increased longevity (average age of death 78.8 vs. 70.4 years,
respectively, p = 0.003). In conclusion, the APC I1307K variant is a reliable
marker for overall cancer risk (OR 2.53). Further studies are needed to evaluate
its use for specific cancer types-particularly in males. Female carriers have
better prognosis and increased lifespan.
PMID- 26421688
TI - Missed Opportunity: Laparoscopic Colorectal Resection Is Associated With Lower
Incidence of Small Bowel Obstruction Compared to an Open Approach.
AB - OBJECTIVE: To investigate the effect of a laparoscopic approach on the rate of
adhesion-related small bowel obstruction (SBO) following colorectal resection.
BACKGROUND: Currently, there is little compelling evidence with regard to rates
of SBO after laparoscopic versus open abdominal surgery. Few studies have
compared risk-adjusted rates of SBO following laparoscopic and open colorectal
resection. METHODS: The Statewide Planning and Research Cooperative System was
queried for elective colorectal resections in New York State from 2003 to 2010. A
propensity score was calculated to account for selection bias between choice of
laparoscopic versus open resection. Bivariate and multivariable competing-risks
models were constructed to assess patient, hospital, surgeon, and operative
characteristics associated with SBO and operation for SBO within 3 years of
resection. RESULTS: Among 69,303 patients who underwent elective colorectal
resection (26% laparoscopic, 74% open), 5.3% of patients developed SBO and 2% of
patients underwent an operation for SBO. After controlling for other risk factors
and conducting an intention-to-treat analysis, open resection was associated with
a higher risk of both SBO [hazard ratio (HR) 1.14, 95% confidence interval (CI)
1.03-1.26] and operation for SBO (HR 1.12, 95% CI 0.94-1.32). This effect was
even greater when characterizing laparoscopic-to-open conversions as an open
approach (SBO: HR 1.34, 95% CI 1.20-1.49; SBO operation: HR 1.35, 95% CI 1.12
1.63). Most other independent risk factors were nonmodifiable and included age
<60, female sex, black race, higher comorbidity burden, previous surgery,
inflammatory bowel disease, and procedure type. CONCLUSIONS: Open colorectal
resection increases the risk of SBO compared with laparoscopy. Increased
utilization of a laparoscopic approach has the potential to achieve a significant
reduction in the incidence of SBO following colorectal resection.
PMID- 26421689
TI - In response to A new theory on the pathogenesis of acquired cholesteatoma:
Mucosal traction.
PMID- 26421690
TI - Paternal and maternal ages have contrasting associations with self-reported
schizophrenia liability.
AB - BACKGROUND: Older paternal age predicts schizophrenia diagnosis in offspring. If
this relationship reflects a pathogenic process, paternal age should predict the
expression of subclinical schizophrenia liability (schizotypy). We hypothesized
that paternal and maternal ages predict positive, negative, and disorganized
features of schizotypy, that family history of psychosis moderates the
relationship of paternal age with schizotypy, and that stress sensitivity
mediates the relationship of maternal age with schizotypy. METHOD: Two studies
are reported, each of undergraduates (n=500 and n=211) who completed the
Schizotypal Personality Questionnaire. The second was designed to replicate and
extend the first and included assessment of stress sensitivity. RESULTS: In Study
1, older paternal age and younger maternal age predicted greater positive
schizotypy (beta=.13 and beta=-.19, respectively). Parental ages did not predict
negative or disorganized features and family history did not moderate the
paternal age association. In Study 2, the same pattern of associations between
parental ages and schizotypy components was observed. Additionally, stress
sensitivity partially mediated the association of maternal age with positive
schizotypy whereas it did not contribute to the paternal age association.
CONCLUSION: The association between older paternal age and schizophrenia extends
to self-reported positive features of schizophrenia liability, consistent with
the notion that this relationship arises from a pathogenic process, such as de
novo mutations. Importantly, younger maternal age was an equally potent predictor
of positive schizotypy, with its association partially mediated by stress
sensitivity.
PMID- 26421691
TI - Linkage and whole genome sequencing identify a locus on 6q25-26 for formal
thought disorder and implicate MEF2A regulation.
AB - Formal thought disorder is a major feature of schizophrenia and other psychotic
disorders. It is heritable, found in healthy relatives of patients with
schizophrenia and other mental disorders but knowledge of specific genetic
factors is lacking. The aim of this study was to search for biologically relevant
high-risk variants. Formal thought disorder was assessed in participants in the
Copenhagen Schizophrenia Linkage Study (N=236), a unique high-risk family study
comprised of six large pedigrees. Microsatellite linkage analysis of formal
thought disorder was performed and subsequent haplotype analysis of the
implicated region using phased microsatellite and SNP genotypes. Whole genome
sequencing (N=3) was used in the attempt to identify causative variants in the
linkage region. Linkage analysis of formal thought disorder resulted in a single
peak at chromosome 6(q26-q27) centred on marker D6S1277, with a maximum LOD score
of 4.0. Phasing and fine mapping of the linkage peak identified a 5.5Mb haplotype
(chr6:162242322-167753547, hg18) in 31 individuals, all belonging to the same
pedigree sharing the haplotype from a common ancestor. The haplotype segregated
with increased total thought disorder index score (P=4.9 * 10(-5)) and
qualitatively severe forms of thought disturbances. Whole genome sequencing
identified a novel nucleotide deletion (chr6:164377205 AG>A, hg18) predicted to
disrupt the potential binding of the transcription factor MEF2A. The MEF2A
binding site is located between two genes previously reported to associate with
schizophrenia, QKI (HGNC:21100) and PDE10A (HGNC:8772). The findings are
consistent with MEF2A deregulation conferring risk of formal thought disorder.
PMID- 26421692
TI - Computerised working-memory focused cognitive remediation therapy for psychosis-
A preliminary study.
AB - BACKGROUND: Cognitive deficits are a core feature of schizophrenia and related
psychotic disorders and are associated with decreased levels of functioning.
Behavioural interventions have shown success in remediating these deficits;
determining how best to maximise this benefit while minimising the cost is an
important next step in optimising this intervention for clinical use. AIMS: To
examine the effects of a novel working-memory focused cognitive remediation (CR)
training on cognitive difficulties based on internet delivery of training and
weekly telephone support. METHOD: Participants with a diagnosis of psychosis
(n=56) underwent either 8 weeks of CR (approximately 20 h) or 8 weeks of
treatment as usual (TAU). General cognitive ability, working memory and episodic
memory were measured both pre and post intervention for all participants.
RESULTS: In addition to improvements on trained working memory tasks, CR training
was associated with significant improvements in two tests of verbal episodic
memory. No association between CR and changes in general cognitive ability was
observed. Effect sizes for statistically significant changes in memory were
comparable to those reported in the literature based primarily on 1:1 training.
CONCLUSIONS: The cognitive benefits observed in this non-randomised preliminary
study indicate that internet-based working memory training can be an effective
cognitive remediation therapy. The successes and challenges of an internet-based
treatment are discussed.
PMID- 26421693
TI - Measuring the impact of burn scarring on health-related quality of life:
Development and preliminary content validation of the Brisbane Burn Scar Impact
Profile (BBSIP) for children and adults.
AB - INTRODUCTION: No burn-scar specific, health-related quality of life (HRQOL)
measure exists. This study aimed to develop a patient-reported, evaluative HRQOL
measure to assess the impact of burn scarring in children and adults. METHOD:
Semi-structured interviews, content validation surveys, and cognitive interviews
were used to develop and test content validity of a new measure - the Brisbane
Burn Scar Impact Profile (BBSIP). RESULTS: Participants comprised Australian
adults (n=23) and children (n=19) with burn scarring; caregivers of children with
burn scarring (n=28); and international scar management experts (n=14). Items
distinct from other burn scar measures emerged. Four versions of the BBSIP were
developed; one for children aged 8-18 years, one for adults, one for caregivers
(as proxies for children aged less than 8-years), and one for caregivers of
children aged 8-18 years. Preliminary content validity of the BBSIP was
supported. Final items covered physical and sensory symptoms; emotional
reactions; impact on social functioning and daily activities; impact of
treatment; and environmental factors. CONCLUSION: The BBSIP was developed to
assess burn-scar specific HRQOL and will be available at
http://www.coolburns.com.au under a creative commons license. Further testing is
underway.
PMID- 26421694
TI - A comparison of non-invasive imaging modalities: Infrared thermography,
spectrophotometric intracutaneous analysis and laser Doppler imaging for the
assessment of adult burns.
AB - BACKGROUND: Currently, the only evidence-based adjunct to clinical evaluation of
burn depth is laser Doppler imaging (LDI), although preliminary studies of
alternative imaging modalities with instant image acquisition are promising. This
is a study to investigate the accuracy of infrared thermography (IRT) and
spectrophotometric intracutaneous analysis (SIA) for burn depth assessment, and
compare this to the current gold standard: LDI. We include a comparison of the
three modalities in terms of cost, reliability and usability. METHODS: We
recruited 20 patients with burns presenting to the Chelsea and Westminster Adult
Burns Service. Between 48h and 5 days afterburn we recorded imaging using
moorLDI2-BI-VR (LDI), FLIR E60 (IRT) and ScanoskinTM (SIA). Subsequent clinical
management and outcome was as normal, and not affected by the extra images taken.
RESULTS: 24 burn regions were grouped according to burn wound healing: group A
healed within 14 days, group B within 14-21 days, and group C took more than 21
days or underwent grafting. Both LDI and IRT accurately determined healing
potential in groups A and C, but failed to distinguish between groups B and C
(p>0.05). ScanoskinTM interpretation of SIA was 100% consistent with clinical
outcome. CONCLUSION: FLIR E60 and ScanoskinTM both present advantages to moorLDI2
BI-VR in terms of cost, ease-of-use and acceptability to patients. IRT is
unlikely to challenge LDI as the gold standard as it is subject to the systematic
bias of evaporative cooling. At present, the LDI colour-coded palette is the
easiest method for image interpretation, whereas ScanoskinTM monochrome colour
palettes are more difficult to interpret. However the additional analyses of
pigment available using SIA may help more accurately indicate the depth of burn
compared with perfusion alone. We suggest development of ScanoskinTM software to
include a simplified colour-palette similar to LDI and additional work to further
investigate the potential of SIA as an alternative to the current gold standard.
PMID- 26421695
TI - The effect of lower body burns on physical function.
AB - OBJECTIVE: To attenuate burn-induced catabolism, patients are often enrolled in a
resistance exercise program as part of their physical rehabilitation. This study
assessed how lower body burn locations affected strength and cardiopulmonary
function. METHODS: Children enrolled in an exercise study between 2003 and 2013,
were 7-18 years of age, and burned >=30% of their total body surface area were
included. Analysis of variance was used to model the relationship of lower body
strength (PTW) and cardiopulmonary function (VO2peak) due to burns which traverse
the subject's lower body joints. RESULTS: There was a significant relationship
between PTW and burns at the hip and toe joints, showing a 26 N m/kg (p=0.010)
and 33 N m/kg (p=0.013) decrease in peak torque, respectively. Burns at the hip
joint corresponded to a significant decrease in VO2peak by 4.9 ml kg(-1) min(-1)
(p=0.010) in peak cardiopulmonary function. CONCLUSION: Physical function and
performance are detrimentally affected by burns that traverse specific lower body
joints. The most significant relationship on exercise performance was that of hip
joint burns as it affected both strength and cardiopulmonary measurements.
Ultimately, burns at hip and toe joints need to be considered when interpreting
exercise test results involving the lower body.
PMID- 26421696
TI - Quantitative breast lesion classification based on multichannel distributions in
shear-wave imaging.
AB - BACKGROUND AND OBJECTIVES: A computer-aided diagnosis (CAD) system based on the
quantified color distributions in shear-wave elastography (SWE) was developed to
evaluate the malignancies of breast tumors. METHODS: For 57 benign and 31
malignant tumors, 18 SWE features were extracted from regions of interest (ROI),
including the tumor and peritumoral areas. In the ROI, a histogram in each color
channel was described using moments such as the mean, variance, skewness, and
kurtosis. Moreover, three color channels were combined as a vector to evaluate
tissue elasticity. The SWE features were then combined in a logistic regression
classifier for breast tumor classification. RESULTS: The performance of the CAD
system achieved an accuracy of 81%. Combining the CAD system with a BI-RADS
assessment obtained an Az improvement from 0.77 to 0.89 (p-value <0.05).
CONCLUSIONS: The combination of the proposed CAD system based on SWE features and
the BI-RADS assessment would provide a promising diagnostic suggestion.
PMID- 26421697
TI - Whole-blood neutrophil gelatinase-associated lipocalin to predict adverse events
in acute kidney injury: A prospective observational cohort study.
AB - PURPOSE: Acute kidney injury is common in intensive care units and is associated
with increased morbidity and mortality. We evaluated the ability of whole-blood
neutrophil gelatinase-associated lipocalin (wbNGAL) to predict mortality and need
for renal replacement therapy (RRT) in critically ill patients with kidney
dysfunction. METHODS: We prospectively enrolled adult patients in 5 Canadian
intensive care units. We measured wbNGAL at the time of enrollment to determine
whether NGAL concentration could predict the primary composite outcome of death
or need for RRT by day 30 in addition to other secondary outcomes. RESULTS: We
recruited 234 patients; 227 were included in the analysis. In a multivariable
model, wbNGAL did not predict 30-day mortality or need for RRT (odds ratio, 1.05;
95% confidence interval, 0.99-1.12). Neutrophil gelatinase-associated lipocalin
was similar in patients who died (654 [303-1180] ng/mL) vs those who survived
(541.5 [255.5-1080] ng/mL, P=.26) by 90 days. Whole-blood NGAL poorly predicted
the primary outcome (area under receiver operator curve, 0.65; 95% confidence
interval, 0.58-0.73). CONCLUSIONS: In a cohort of critically ill patients with
abnormal kidney function, wbNGAL was not effective in the prediction of death or
RRT within 30 days. These data do not support the use of this biomarker for the
detection of clinical outcomes in this population.
PMID- 26421698
TI - Complications of 761 short-term intrathecal macrocatheters in obstetric patients:
a retrospective review of cases over a 12-year period.
AB - BACKGROUND: A continuous spinal catheter is a reliable alternative to standard
neuraxial techniques in obstetric anesthesia. Despite the potential advantages of
intrathecal catheters, they remain underutilized due to fear of infection, nerve
damage or post-dural puncture headache. In our tertiary care center, intrathecal
catheters are either placed intentionally in high-risk obstetric patients or
following inadvertent dural puncture using a 19-gauge macrocatheter passed
through a 17-gauge epidural needle. METHODS: A retrospective review of 761
intrathecal catheters placed from 2001 to 2012 was conducted. An institutional
obstetric anesthesia database was used to identify patients with intrathecal
catheters. Medical records were reviewed for procedural details and
complications. RESULTS: There were no serious complications, including
meningitis, epidural or spinal abscess, hematoma, arachnoiditis, or cauda equina
syndrome, associated with intrathecal catheters. The failure rates were 2.8%
(3/108) for intentional placements and 6.1% (40/653) for placements following
accidental dural puncture. The incidence of post-dural puncture headache was 41%
(312/761) and the epidural blood patch rate was 31% (97/312). CONCLUSIONS: This
review demonstrates that intrathecal catheters are dependable and an option for
labor analgesia and surgical anesthesia for cesarean delivery. Serious long
lasting complications are rare.
PMID- 26421699
TI - Management of the obstetric airway - time for a paradigm shift (or two)?
PMID- 26421700
TI - A randomised controlled trial of the effect of a head-elevation pillow on
intrathecal local anaesthetic spread in caesarean section.
AB - BACKGROUND: A head-elevation pillow places a patient in a ramped posture, which
maximises the view of the larynx during laryngoscopy, particularly in obese
parturients. In our institution an elevation pillow is used pre-emptively for
neuraxial anaesthesia. We hypothesised that head-elevation may impair cephalad
spread of local anaesthetic before caesarean section resulting in a lower block
or longer time to achieve a T6 level. We aimed to investigate the effect of head
elevation on spread of intrathecal local anaesthetics during anaesthesia for
caesarean section. METHODS: One-hundred parturients presenting for caesarean
section under combined spinal-epidural anaesthesia were randomised to either the
standard supine position with lateral displacement or in the supine position with
lateral displacement on an head-elevation pillow. Each patient received
intrathecal hyperbaric bupivacaine 11 mg, morphine 100 MUg and fentanyl 15 MUg.
Patients were assessed for adequacy of sensory block (T6 or higher) at 10 min.
RESULTS: Sensory block to T6 was achieved within 10 min in 65.9% of parturients
in the Elevation Pillow Group compared to 95.7% in the Control Group (P<0.05).
Compared to the Control Group, patients in the Elevation Pillow Group had greater
requirements for epidural supplementation (43.5% vs 2.1%, P<0.001) or conversion
to general anaesthesia (9.3% vs 0%, P<0.04). CONCLUSIONS: Use of a ramped
position with an head-elevation pillow following injection of the intrathecal
component of a combined spinal-epidural anaesthetic for scheduled caesarean
section was associated with a significantly lower block height at 10min.
PMID- 26421701
TI - Effects of prophylactic ondansetron on spinal anesthesia-induced hypotension: a
meta-analysis.
AB - BACKGROUND: A range of strategies including physical interventions, intravenous
fluids and vasopressor drugs have been used to minimize or prevent spinal
anesthesia-induced hypotension. Recent studies suggest that ondansetron, a
commonly used antiemetic, also affects hypotension. This systematic review
investigated the effects of prophylactic ondansetron on hemodynamic changes
following spinal anesthesia. METHODS: Medline, Embase, Cochrane Library databases
and www.clinicaltrials.gov were searched for randomized controlled trials
studying the effects of ondansetron on hemodynamic changes induced by spinal
anesthesia. The primary outcome was hypotension. Relative risk (RR) or mean
difference, with 95% confidence intervals (CI), were used to analyze outcomes.
RESULTS: Ten randomized controlled trials with 863 patients were included in the
analysis. Prophylactic ondansetron reduced the incidence of spinal anesthesia
induced hypotension in both obstetric and non-obstetric patients. The RR of
spinal anesthesia-induced hypotension after ondansetron administration was 0.53
(95% CI 0.32 to 0.86) in obstetric patients and 0.16 (95% CI 0.05 to 0.51) in non
obstetric patients. There was significant heterogeneity among obstetric studies
(I(2) = 71%). Ondansetron also reduced the incidence of bradycardia, nausea and
vomiting after spinal anesthesia with RRs of 0.27 (95% CI 0.16 to 0.47), 0.24
(95% CI 0.14 to 0.42) and 0.48 (95% CI 0.08 to 3.08), respectively. The doses of
ephedrine and phenylephrine required to treat hypotension were reduced by
ondansetron with mean differences of -2.35 mg (95% CI -4.14 to -0.55 mg) and
31.16 MUg (95% CI -57.46 to -4.87 MUg), respectively. CONCLUSION: This review
suggests that prophylactic ondansetron reduces the incidence of spinal anesthesia
induced hypotension and vasopressor consumption in both obstetric and non
obstetric patients. In addition, ondansetron can also reduce related adverse
outcomes such as bradycardia, nausea and vomiting. However, given the relatively
large heterogeneity and small sample sizes in current studies, further large and
strict randomized clinical trials investigating the effects of ondansetron on
spinal anesthesia-induced hemodynamic changes and side effects are still needed,
especially among obstetric patients.
PMID- 26421702
TI - The use of phenylephrine to obtund oxytocin-induced hypotension and tachycardia
during caesarean section.
AB - BACKGROUND: Oxytocin causes clinically significant hypotension and tachycardia.
This study examined whether prior administration of phenylephrine obtunds these
unwanted haemodynamic effects. METHODS: Forty pregnant women undergoing elective
caesarean section under spinal anaesthesia were randomised to receive either an
intravenous 50 MUg bolus of phenylephrine (Group P) or saline (Group S)
immediately before oxytocin (3U over 15s). Systolic blood pressure, diastolic
blood pressure, mean arterial pressure and heart rate were recorded using a
continuous non-invasive arterial pressure device. Baseline values were averaged
for 20s post-delivery. Between-group comparisons were made of the mean peak
changes in blood pressure and heart rate, and the mean percentage changes from
baseline, during the 150s after oxytocin administration. RESULTS: The mean +/- SD
peak percentage change in systolic blood pressure was -16.9 +/- 2% in Group P,
and -19.0 +/- 1.9% in Group S and the estimated mean difference was 2.1% (95% CI
3.5% to 7.8%; P=0.44); corresponding changes in heart rate were 13.5 +/- 2.3% and
14.0+/-1.5% and the mean estimated difference was 0.5% (95% CI -6.0% to 5%;
P=0.87). The mean percentage change from the baseline measurements during the
150s period of measurement was greater for Group S than Group P: systolic blood
pressure -5.9% vs -3.4% (P=0.149); diastolic blood pressure -7.2% vs -1.5%
(P=0.014); mean arterial pressure -6.8% vs -1.5% (P=0.007); heart rate 2.1% vs
2.4% (P=0.033). CONCLUSION: Intravenous phenylephrine 50 MUg immediately before
3U oxytocin during elective caesarean section does not prevent maternal
hypotension and tachycardia.
PMID- 26421703
TI - The extension of epidural blockade for emergency caesarean section: a survey of
Scandinavian practice.
AB - BACKGROUND: Little is known about drugs and safety precautions used during
epidural top-ups for emergency caesarean section in Scandinavia. We surveyed
Scandinavian practice of epidural top-up regimens for emergency caesarean
sections. METHODS: Anaesthetic departments in Denmark, Norway and Sweden were
identified via National Boards of Health. An electronic questionnaire was sent to
Scandinavian specialist anaesthesiologists performing obstetric anaesthesia
asking for information on anaesthetic practice for emergency caesarean section.
RESULTS: The response rate was 80% (n=145). One hundred and twenty (83%)
specialists reported the existence of local guidelines for epidural top-ups.
Fourteen (9.7%) specialists gave a full-dose top-up in the delivery room, 34
(23.4%) initiated the top-up with a test-dose, and 87 (60%) only administered
local anaesthetics in the operating theatre. Twenty-five different drug
combinations for epidural top-ups were reported. Lidocaine was used by 67 (47.9%)
and ropivacaine was used by 53 (37.9%). Seventy (50%) specialists added opioid to
the top-up, 15 (10.7%) added bicarbonate and 53 (37.9%) supplemented with
adrenaline. Median top-up volume ranged from 16 to 19mL for lidocaine,
ropivacaine and chloroprocaine. One-hundred-and-eighteen (81%) specialists
recommended trainees use the same regimen. Forty (83%) of 48 specialists topping
up in the labour unit had ephedrine readily available. During transport, pulse
oximetry was used by nine (19%) and non-invasive blood pressure monitoring by
eight (17%). CONCLUSIONS: Epidural top-ups for emergency caesarean section in
Scandinavia are used frequently but normally performed in the operating theatre.
Drugs used differ greatly between countries and departments although top-up
volumes appear similar. During transport, available equipment and drugs were
limited. Best practice guidelines and national guidelines present little
information on epidural top-ups that could explain the variation found.
PMID- 26421704
TI - Phenylephrine infusion test to evaluate alpha blockade in a pregnant patient with
pheochromocytoma.
PMID- 26421705
TI - Checklists and multidisciplinary team performance during simulated obstetric
hemorrhage.
AB - BACKGROUND: Checklists can optimize team performance during medical crises.
However, there has been limited examination of checklist use during obstetric
crises. In this simulation study we exposed multidisciplinary teams to checklist
training to evaluate checklist use and team performance during a severe
postpartum hemorrhage. METHODS: Fourteen multidisciplinary teams participated in
a postpartum hemorrhage simulation occurring after vaginal delivery. Before
participating, each team received checklist training. The primary study outcome
was whether each team used the checklist during the simulation. Secondary
outcomes were the times taken to activate our institution-specific massive
transfusion protocol and commence red blood cell transfusion, and whether a
designated checklist reader was used. RESULTS: The majority of teams (12/14
(86%)) used the checklist. Red blood cell transfusion was administered by all
teams. The median [IQR] times taken to activate the massive transfusion protocol
and transfuse red blood cells were 5min 14s [3:23-6:43] and 14min 40s [12:56
17:28], respectively. A designated checklist reader was used by 7/12 (58%) teams
that used the checklist. Among teams that used a checklist with versus without a
designated reader, we observed no differences in the times to activate the
massive transfusion protocol or to commence red blood cell transfusion (P>0.05).
CONCLUSIONS: Although checklist training was effective in promoting checklist
use, multidisciplinary teams varied in their scope of checklist use during a
postpartum hemorrhage simulation. Future studies are required to determine
whether structured checklist training can result in more standardized checklist
use during a postpartum hemorrhage.
PMID- 26421706
TI - The Psychosocial and Clinical Outcomes of Orbital Decompression Surgery for
Thyroid Eye Disease and Predictors of Change in Quality of Life.
AB - PURPOSE: Thyroid eye disease (TED) has been found to reduce quality of life for
many patients because of changes in their appearance and vision, although some
seem to adjust better than others. This study was designed to investigate whether
a patient's quality of life changes after having orbital decompression for
improvement of appearance, vision, or both, and whether any demographic,
clinical, or psychosocial factors can predict which patients might benefit from
this surgery. DESIGN: This study used a within-subjects repeated-measures design,
in which patients were assessed before and at 6 weeks and 6 months after surgery.
PARTICIPANTS: A total of 123 adults (aged >18 years) with TED and undergoing
orbital decompression surgery were recruited at Moorfields Eye Hospital. METHODS:
Participants received lateral wall, medial wall, 2.5 wall, or 3 wall
decompression and were followed up after surgery with a range of psychosocial and
clinical assessments. MAIN OUTCOME MEASURES: The Graves' Ophthalmopathy Quality
of Life (GO-QOL) scale was completed at each time point, and this was used as the
dependent variable in each hierarchical multiple regression model. RESULTS:
Significant improvements were found in all clinical characteristics after orbital
decompression and in most psychosocial variables. The GO-QOL visual function
scores did not change significantly until 6 months after surgery. In contrast, GO
QOL appearance scores changed significantly by 6 weeks after surgery and
continued to increase to 6 months, reaching a minimal clinically important
difference for this scale. None of the changes in clinical or psychosocial
outcomes significantly predicted change in GO-QOL visual function. However, the
hierarchical regression model explained 79% of the variance in change in GO-QOL
appearance, with change in subjective evaluation of appearance being the only
unique predictor of change in appearance-related quality of life. CONCLUSIONS:
This study highlights the importance of appearance-related cognitions in
predicting quality of life outcomes after surgery. Implications for clinical
practice need to be considered in light of the limitations of this study, but it
is suggested that psychosocial interventions targeting appearance-related
cognitive processes, in particular personal evaluation of appearance, could
enhance the quality of life outcomes for patients with TED undergoing orbital
decompression surgery.
PMID- 26421707
TI - Importance of Normal Aging in Estimating the Rate of Glaucomatous Neuroretinal
Rim and Retinal Nerve Fiber Layer Loss.
AB - PURPOSE: To describe longitudinal rates of change of neuroretinal parameters in
patients with glaucoma and healthy controls, and to evaluate the influence of
covariates. DESIGN: Prospective longitudinal study. PARTICIPANTS: Treated
patients with glaucoma (n = 192) and healthy controls (n = 37). METHODS: Global
disc margin-based neuroretinal rim area (DMRA) was measured with confocal
scanning laser tomography, while Bruch's membrane opening-minimum rim width (BMO
MRW), BMO area (BMOA), and peripapillary retinal nerve fiber layer thickness
(RNFLT) were measured with optical coherence tomography at 6-month intervals.
Individual rates of change were estimated with ordinary least-squares regression,
and linear mixed effects modeling was used to estimate the average rate of change
and differences between the groups, and to evaluate the effects of baseline
measurement and baseline age on rates of change. MAIN OUTCOME MEASURES: Rates of
change for each parameter. RESULTS: Subjects were followed for a median (range)
of 4 (2-6) years. The proportion of controls who had significant reduction of
neuroretinal parameters was 35% for BMO-MRW, 31% for RNFLT, and 11% for DMRA. The
corresponding figures for patients with glaucoma were not statistically different
(42%, P = 0.45; 31%, P = 0.99; 14%, P = 0.99, respectively). Controls had a
significant reduction of BMO-MRW (mean: -1.92 MUm/year, P < 0.01) and RNFLT
(mean: -0.44 MUm/year, P = 0.01), but not DMRA (mean: -0.22*10(-2) mm(2)/year, P
= 0.41). After adjusting for covariates, patients with glaucoma had faster, but
not statistically different, rates of deterioration compared with controls, by
1.26 MUm/year (P = 0.07) for BMO-MRW, -0.40 MUm/year (P = 0.11) for RNFLT, and
0.38*10(-2) mm(2)/year (P = 0.23) for DMRA. Baseline BMO-MRW and RNFLT
significantly influenced the respective rates of change, with higher baseline
values relating to faster reductions. Older age at baseline was associated with a
slower reduction in rates of BMO-MRW. Reductions in intraocular pressure were
related to increases in BMO-MRW and DMRA. There was a tendency for BMOA to
decrease over time (-0.38*10(-2) mm(2)/year; P = 0.04). CONCLUSIONS: Age-related
loss of neuroretinal parameters may explain a large proportion of the
deterioration observed in treated patients with glaucoma and should be carefully
considered in estimating rates of change.
PMID- 26421708
TI - Short-term outcomes of intracorporeal esophagojejunostomy using the transorally
inserted anvil versus extracorporeal circular anastomosis during laparoscopic
total gastrectomy for gastric cancer: a propensity score matching analysis.
AB - BACKGROUND: To assess the short-term outcomes of intracorporeal Roux-en-Y
esophagojejunostomy using the transorally inserted anvil (OrVil) compared with
extracorporeal circular Roux-en-Y anastomosis during laparoscopic total
gastrectomy (LTG) for gastric cancer. METHODS: From January 2011-April 2014, a
total of 165 consecutive patients with gastric cancer underwent either
intracorporeal Roux-en-Y esophagojejunostomy (n = 25) using the Orvil or
extracorporeal circular anastomosis (n = 140) during LTG. After generating
propensity scores with six covariates, including gender, age, body mass index
(BMI), Eastern Cooperative Oncology Group performance status, tumor location, and
tumor size, 25 patients undergoing the OrVil method (intracorporeal group) were
one-to-one matched with 25 patients undergoing the extracorporeal method
(extracorporeal group). The short-term outcomes were compared between the two
groups. RESULTS: Both groups were balanced regarding baseline variables. The
total operative time was not significantly different between the two groups
(216.5 +/- 24.9 min versus 224.0 +/- 30.5 min, P = 0.344), whereas either the
duration of anvil insertion (9.9 +/- 2.4 min versus 12.9 +/- 2.0 min, P < 0.001)
or reconstruction completion (44.4 +/- 9.4 min versus 50.1 +/- 5.4 min, P =
0.012) in the intracorporeal group was less. The mean length of minilaparotomy in
the intracorporeal group was shorter (5.6 +/- 0.4 cm versus 7.2 +/- 1.7 cm, P <
0.001). No significant differences were observed in intraoperative complication
rate, estimated blood loss, length of proximal margin, or postoperative recovery
course (including the time to first flatus, liquid resumption, liquid, and soft
diet) between the two groups. No patients suffered from anastomosis-related
complications. The overall morbidity rates of 28.0% in the intracorporeal group
and 32.0% in the extracorporeal group were comparable (P = 0.758). CONCLUSIONS:
Intracorporeal Roux-en-Y esophagojejunostomy using the transorally inserted anvil
system may be a safe procedure during LTG for gastric cancer. However, a longer
follow-up in a well-designed randomized controlled trial is necessary to more
thoroughly evaluate this technique.
PMID- 26421709
TI - Decellularized amniotic membrane attenuates postinfarct left ventricular
remodeling.
AB - BACKGROUND: Placenta and amnion have been suggested as sources of juvenile cells
and tissues for use in surgical regenerative medicine. We previously determined
the impact of amniotic epithelial cells induced to undergo epithelial-to
mesenchymal transition (EMT) on myocardial remodeling processes and now evaluated
the effects of naive and processed amniotic membrane (AM) on postischemic left
ventricular (LV) geometry and function. METHODS: Human AM was used in unmodified
form (AM), after EMT induction by transforming growth factor beta (EMT-AM), and
after decellularization (Decell-AM). After characterization by histology,
electron microscopy, splenocyte proliferation assay, and cytokine release,
myocardial infarction was induced in 6-8-week old male BALB/c mice by permanent
left anterior descending coronary occlusion, and AM patches were sutured to the
anterior LV surface (n = 10 per group). Infarcted hearts without AM or sham
operated mice were used as controls (n = 10 each). After 4 weeks, LV pressure
volume curves were recorded using a conductance catheter before the animals were
sacrificed and the hearts analyzed by histology. RESULTS: TGF-beta treatment
induced EMT-like changes in amniotic epithelial cells but increased AM
xenoreactivity in vitro (splenocyte proliferation) and in vivo (CD4+ cell
invasion). Moreover, in vitro interleukin-6 release from AM and from cardiac
fibroblasts co-incubated with AM was 300- or 100-fold higher than that of
interleukin-10, whereas Decell-AM did not release any cytokines. AM- and Decell
AM-treated hearts had smaller infarct size and greater infarct scar thickness
than infarct control hearts, but there was no difference in myocardial capillary
density or the number of TUNEL positive apoptotic cells. LV contractile function
was better in the AM and EMT-AM groups than in infarcted control hearts, but
dP/dt max, dP/dt min, stroke work, and cardiac output were best preserved in mice
treated with Decell-AM. Volume-based parameters (LV end-systolic and end
diastolic volume as well as LV ejection fraction) did not differ between AM and
Decell-AM. CONCLUSIONS: Decellularized AM supports postinfarct ventricular
dynamics independent of the actual regeneration processes. As a cell-free
approach to support the infarcted heart, this concept warrants further
investigation.
PMID- 26421710
TI - High mitochondrial mass identifies a sub-population of stem-like cancer cells
that are chemo-resistant.
AB - Chemo-resistance is a clinical barrier to more effective anti-cancer therapy. In
this context, cancer stem-like cells (CSCs) are thought to be chemo-resistant,
resulting in tumor recurrence and distant metastasis. Our hypothesis is that
chemo-resistance in CSCs is driven, in part, by enhanced mitochondrial function.
Here, we used breast cell lines and metastatic breast cancer patient samples to
begin to dissect the role of mitochondrial metabolism in conferring the CSC
phenotype. More specifically, we employed fluorescent staining with MitoTracker
(MT) to metabolically fractionate these cell lines into mito-high and mito-low
sub-populations, by flow-cytometry. Interestingly, cells with high mitochondrial
mass (mito-high) were specifically enriched in a number of known CSC markers,
such as aldehyde dehydrogenase (ALDH) activity, and they were ESA+/CD24-/low and
formed mammospheres with higher efficiency. Large cell size is another
independent characteristic of the stem cell phenotype; here, we observed a >2
fold increase in mitochondrial mass in large cells (>12-MUm), relative to the
smaller cell population (4-8-MUm). Moreover, the mito-high cell population showed
a 2.4-fold enrichment in tumor-initiating cell activity, based on limiting
dilution assays in murine xenografts. Importantly, primary human breast CSCs
isolated from patients with metastatic breast cancer or a patient derived
xenograft (PDX) also showed the co-enrichment of ALDH activity and mitochondrial
mass. Most significantly, our investigations demonstrated that mito-high cells
were resistant to paclitaxel, resulting in little or no DNA damage, as measured
using the comet assay. In summary, increased mitochondrial mass in a sub
population of breast cancer cells confers a stem-like phenotype and chemo
resistance. As such, our current findings have important clinical implications
for over-coming drug resistance, by therapeutically targeting the mito-high CSC
population.
PMID- 26421713
TI - The design and implementation of an accelerometer-assisted velocity observer.
AB - This paper presents a dynamically compensated velocity observer (DCVO), in which
acceleration measurement is employed to estimate velocity. Its sensitivity to the
noise that is associated with the acceleration measurement is formulated and
compared with that of a conventional state-space velocity observer (SSVO). Unlike
the SSVO, the DCVO is completely insensitive to an accelerometer offset. The
DCVO, the SSVO and a common ITM-based estimator are all realized in a linear
motion stage, to determine their effectiveness. A sliding-mode controller is also
implemented with different velocity observers, and it is shown that the DCVO
enables high-frequency switching of the sliding-mode controller and also
practically improves the positioning accuracy.
PMID- 26421712
TI - The MTHFR C677T Polymorphism Is Related to Plasma Concentration of Oxidized Low
Density Lipoprotein in Adolescents with Cardiovascular Risk Factors.
AB - AIM: The aim of this study was to investigate possible relationships among the
A1298C (rs1801131) and C677T (rs1801133) polymorphisms in the
methylenetetrahydrofolate reductase (MTHFR) gene and levels of homocysteine,
vitamins B6, B12, folic acid and lipid profile, including oxidized low-density
lipoprotein (ox-LDL), of adolescents at cardiovascular risk. METHODS: We
recruited 115 adolescents (10-19 years old), 58.3% (n = 67) female, from a public
school in Brazil who underwent anthropometric, biochemical and genetic tests as
well as food consumption evaluation. RESULTS: An important prevalence of
hyperhomocysteinemia (19.1%) and alterations in triacylglycerol (17.4%), total
cholesterol (26.9%) and high-density lipoprotein (HDL) cholesterol (48.0%)
concentrations were observed, as well as low vitamin B6 concentrations (23.5%).
The categorization of homocysteine concentrations into tertiles revealed
significant differences in serum concentrations of folate, vitamin B12 and HDL,
waist circumference and intake of total and saturated fat among the tertiles. The
presence of variant alleles regarding the MTHFR C677T polymorphism interfered
with vitamin B6 and ox-LDL cholesterol concentrations. There was a trend for
higher waist circumference values in T carriers (C677T), but not in C carriers
(A1298C). CONCLUSIONS: The MTHFR C677T allele was associated with higher plasma
vitamin B6 and ox-LDL compared to the CC genotype.
PMID- 26421714
TI - Coarctate and Pseudocoarctate Reactions: Stereochemical Rules.
AB - Coarctate reactions are a distinct class of concerted reactions. They differ from
other concerted reactions, such as S(N)2, E2, or pericyclic reactions, in such a
way that atoms are involved in the transition state at which two bonds are made
and two bonds are broken simultaneously. Similar to pericyclic reactions, an
electron count can be used to predict reactivity and stereochemistry. The
"coarctate rules" are derived from a topological variant of the aromaticity of
the transition state principle. Pseudocoarctate transition states exhibit
disconnections in the topology of orbital overlap and do not necessarily follow
the coarctate rules.
PMID- 26421711
TI - Mitochondrial mass, a new metabolic biomarker for stem-like cancer cells:
Understanding WNT/FGF-driven anabolic signaling.
AB - Here, we developed an isogenic cell model of "stemness" to facilitate protein
biomarker discovery in breast cancer. For this purpose, we used knowledge gained
previously from the study of the mouse mammary tumor virus (MMTV). MMTV initiates
mammary tumorigenesis in mice by promoter insertion adjacent to two main
integration sites, namely Int-1 (Wnt1) and Int-2 (Fgf3), which ultimately
activates Wnt/beta-catenin signaling, driving the propagation of mammary cancer
stem cells (CSCs). Thus, to develop a humanized model of MMTV signaling, we over
expressed WNT1 and FGF3 in MCF7 cells, an ER(+) human breast cancer cell line. We
then validated that MCF7 cells over-expressing both WNT1 and FGF3 show a 3.5-fold
increase in mammosphere formation, and that conditioned media from these cells is
also sufficient to promote stem cell activity in untransfected parental MCF7 and
T47D cells, as WNT1 and FGF3 are secreted factors. Proteomic analysis of this
model system revealed the induction of i) EMT markers, ii) mitochondrial
proteins, iii) glycolytic enzymes and iv) protein synthesis machinery, consistent
with an anabolic CSC phenotype. MitoTracker staining validated the expected
WNT1/FGF3-induced increase in mitochondrial mass and activity, which presumably
reflects increased mitochondrial biogenesis. Importantly, many of the proteins
that were up-regulated by WNT/FGF-signaling in MCF7 cells, were also
transcriptionally over-expressed in human breast cancer cells in vivo, based on
the bioinformatic analysis of public gene expression datasets of laser-captured
patient samples. As such, this isogenic cell model should accelerate the
discovery of new biomarkers to predict clinical outcome in breast cancer,
facilitating the development of personalized medicine.Finally, we used
mitochondrial mass as a surrogate marker for increased mitochondrial biogenesis
in untransfected MCF7 cells. As predicted, metabolic fractionation of parental
MCF7 cells, via MitoTracker staining, indicated that high mitochondrial mass is a
new metabolic biomarker for the enrichment of anabolic CSCs, as functionally
assessed by mammosphere-forming activity. This observation has broad implications
for understanding the role of mitochondrial biogenesis in the propagation of stem
like cancer cells. Technically, this general metabolic approach could be applied
to any cancer type, to identify and target the mitochondrial-rich CSC
population.The implications of our work for understanding the role of
mitochondrial metabolism in viral oncogenesis driven by random promoter
insertions are also discussed, in the context of MMTV and ALV infections.
PMID- 26421715
TI - Histological and morphological observations on tongue of Scincella tsinlingensis
(Reptilia, Squamata, Scincidae).
AB - The histology and morphology characteristics of the tongue in Scincella
tsinlingensis were studied by light and electronic microscopy. Under light
microscopy, the tongue consists of tip, lingual body and radix in sequence.
Numerous lingual papillae widely distribute on the surface of the dorsal and
ventral flanks in the tongue, in addition to some regions of the tip. The
papillae's surface is covered with the epithelial layer. The lamina propria and
dense connective tissue are distinct existing under the epithelial layer. There
are many lingual glands spread over the lamina propria. Tongue muscle is
developed and composed of distinct intrinsic muscle, hyoglossus and genioglossus.
By scanning electron microscopy, at higher magnification, the epithelial cells of
the dorsal surface in the divaricate tongue tips show numerous microvilli, micro
ridges and micro-pores. The surface of dorsal side of the papillae in lingual
body is covered with abundant of micro-ridges and taste bud lacuna. On the
surface of the papillae in radix, micro-facets and micro-ridges are compactly
distributed, as well as scattered mucilage-pores. The lingual epithelium is
divided into four layers observed by the transmission electron microscope. Cells
of basal layer are irregularly elliptical in shape, with sparse organelles in the
cytoplasm. The deep intermediate layer is not always distinct. Small numbers of
organelles are scattered into the cytoplasm. The cells of the superficial
intermediate layer gradually flatten, as do their nuclei. The cytoplasm contains
many keratohyalin granules. Cell membranes are formed processes around cells and
joined by abundant desmosomes to the cell membranes of adjacent cells. The cells
located on the extreme free-surface side of the keratinized layer have fallen
off. The basal lamina is intercalated between the basal layer and the lamina
propria. The lamina propria of lingual body contains lingual gland. A large part
of the cytoplasm is occupied by mucus granules which located in the distal part
of the cell. The connective tissue contains myelinated nerve fibers, vessel and
muscle cells.
PMID- 26421716
TI - Microbiological Evaluation of Household Drinking Water Treatment in Rural China
Shows Benefits of Electric Kettles: A Cross-Sectional Study.
AB - BACKGROUND: In rural China ~607 million people drink boiled water, yet little is
known about prevailing household water treatment (HWT) methods or their
effectiveness. Boiling, the most common HWT method globally, is microbiologically
effective, but household air pollution (HAP) from burning solid fuels causes
cardiovascular and respiratory disease, and black carbon emissions exacerbate
climate change. Boiled water is also easily re-contaminated. Our study was
designed to identify the HWT methods used in rural China and to evaluate their
effectiveness. METHODS: We used a geographically stratified cross-sectional
design in rural Guangxi Province to collect survey data from 450 households in
the summer of 2013. Household drinking water samples were collected and assayed
for Thermotolerant Coliforms (TTC), and physicochemical analyses were conducted
for village drinking water sources. In the winter of 2013-2104, we surveyed 120
additional households and used remote sensors to corroborate self-reported
boiling data. FINDINGS: Our HWT prevalence estimates were: 27.1% boiling with
electric kettles, 20.3% boiling with pots, 34.4% purchasing bottled water, and
18.2% drinking untreated water (for these analyses we treated bottled water as a
HWT method). Households using electric kettles had the lowest concentrations of
TTC (73% lower than households drinking untreated water). Multilevel mixed
effects regression analyses showed that electric kettles were associated with the
largest Log10TTC reduction (-0.60, p<0.001), followed by bottled water (-0.45,
p<0.001) and pots (-0.44, p<0.01). Compared to households drinking untreated
water, electric kettle users also had the lowest risk of having TTC detected in
their drinking water (risk ratio, RR = 0.49, 0.34-0.70, p<0.001), followed by
bottled water users (RR = 0.70, 0.53-0.93, p<0.05) and households boiling with
pots (RR = 0.74, 0.54-1.02, p = 0.06). CONCLUSION: As far as we are aware, this
is the first HWT-focused study in China, and the first to quantify the
comparative advantage of boiling with electric kettles over pots. Our results
suggest that electric kettles could be used to rapidly expand safe drinking water
access and reduce HAP exposure in rural China.
PMID- 26421717
TI - Calmodulin Interacts with the Sodium/Calcium Exchanger NCX1 to Regulate Activity.
AB - Changes in intracellular Ca2+ concentrations ([Ca2+]i) are an important signal
for various physiological activities. The Na+/Ca2+ exchangers (NCX) at the plasma
membrane transport Ca2+ into or out of the cell according to the electrochemical
gradients of Na+ and Ca2+ to modulate [Ca2+]i homeostasis. Calmodulin (CaM)
senses [Ca2+]i changes and relays Ca2+ signals by binding to target proteins such
as channels and transporters. However, it is not clear how calmodulin modulates
NCX activity. Using CaM as a bait, we pulled down the intracellular loops
subcloned from the NCX1 splice variants NCX1.1 and NCX1.3. This interaction
requires both Ca2+ and a putative CaM-binding segment (CaMS). To determine
whether CaM modulates NCX activity, we co-expressed NCX1 splice variants with CaM
or CaM1234 (a Ca2+-binding deficient mutant) in HEK293T cells and measured the
increase in [Ca2+]i contributed by the influx of Ca2+ through NCX. Deleting the
CaMS from NCX1.1 and NCX1.3 attenuated exchange activity and decreased membrane
localization. Without the mutually exclusive exon, the exchange activity was
decreased and could be partially rescued by CaM1234. Point-mutations at any of
the 4 conserved a.a. residues in the CaMS had differential effects in NCX1.1 and
NCX1.3. Mutating the first two conserved a.a. in NCX1.1 decreased exchange
activity; mutating the 3rd or 4th conserved a.a. residues did not alter exchange
activity, but CaM co-expression suppressed activity. Mutating the 2nd and 3rd
conserved a.a. residues in NCX1.3 decreased exchange activity. Taken together,
our results demonstrate that CaM senses changes in [Ca2+]i and binds to the
cytoplasmic loop of NCX1 to regulate exchange activity.
PMID- 26421718
TI - Whole Genomic Analysis of an Unusual Human G6P[14] Rotavirus Strain Isolated from
a Child with Diarrhea in Thailand: Evidence for Bovine-To-Human Interspecies
Transmission and Reassortment Events.
AB - An unusual rotavirus strain, SKT-27, with the G6P[14] genotypes (RVA/Human
wt/THA/SKT-27/2012/G6P[14]), was identified in a stool specimen from a
hospitalized child aged eight months with severe diarrhea. In this study, we
sequenced and characterized the complete genome of strain SKT-27. On whole
genomic analysis, strain SKT-27 was found to have a unique genotype
constellation: G6-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. The non-G/P genotype
constellation of this strain (I2-R2-C2-M2-A3-N2-T6-E2-H3) is commonly shared with
rotavirus strains from artiodactyls such as cattle. Phylogenetic analysis
indicated that nine of the 11 genes of strain SKT-27 (VP7, VP4, VP6, VP2-3, NSP1,
NSP3-5) appeared to be of artiodactyl (likely bovine) origin, while the remaining
VP1 and NSP2 genes were assumed to be of human origin. Thus, strain SKT-27 was
found to have a bovine rotavirus genetic backbone, and thus is likely to be of
bovine origin. Furthermore, strain SKT-27 appeared to be derived through
interspecies transmission and reassortment events involving bovine and human
rotavirus strains. Of note is that the VP7 gene of strain SKT-27 was located in
G6 lineage-5 together with those of bovine rotavirus strains, away from the
clusters comprising other G6P[14] strains in G6 lineages-2/6, suggesting the
occurrence of independent bovine-to-human interspecies transmission events. To
our knowledge, this is the first report on full genome-based characterization of
human G6P[14] strains that have emerged in Southeast Asia. Our observations will
provide important insights into the origin of G6P[14] strains, and into dynamic
interactions between human and bovine rotavirus strains.
PMID- 26421720
TI - Utilization of bone impedance for age estimation in postmortem cases.
AB - In the field of Forensic Medicine the number of unidentified cadavers has
increased due to natural disasters and international terrorism. The age
estimation is very important for identification of the victims. The degree of
sagittal closure is one of such age estimation methods. However it is not widely
accepted as a reliable method for age estimation. In this study, we have examined
whether measuring impedance value (z-values) of the sagittal suture of the skull
is related to the age in men and women and discussed the possibility to use bone
impedance for age estimation. Bone impedance values increased with aging and
decreased after the age of 64.5. Then we compared age estimation through the
conventional visual method and the proposed bone impedance measurement technique.
It is suggested that the bone impedance measuring technique may be of value to
forensic science as a method of age estimation.
PMID- 26421719
TI - Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in
Mice and Modulation by Rikkunshito.
AB - Abdominal surgery inhibits food intake and induces c-Fos expression in the
hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine
improves anorexia. We assessed the alterations in meal microstructure and c-Fos
expression in brain nuclei induced by abdominal surgery and the modulation by RKT
in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access
to food for 6-7 h and were treated twice with RKT or vehicle. Abdominal surgery
(laparotomy-cecum palpation) was performed 1-2 h before the dark phase. The food
intake and meal structures were monitored using an automated monitoring system
for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after
abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency,
size and duration, and time spent on meals, and increased inter-meal interval and
satiety ratio resulting in 92-86% suppression of food intake at 2-24 h post
surgery compared with control group (no surgery). RKT significantly increased
bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal
surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and
autonomic nuclei, such as the bed nucleus of the stria terminalis, central
amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei,
Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral
parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus
solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and
E-W of control mice, and in mice with surgery there was an increase in the
lateral PAG and a decrease in the NTS. These findings indicate that abdominal
surgery inhibits food intake by increasing both satiation (meal duration) and
satiety (meal interval) and activates brain circuits involved in pain, feeding
behavior and stress that may underlie the alterations of meal pattern and food
intake inhibition. RKT improves food consumption post-surgically that may involve
modulation of pain pathway.
PMID- 26421721
TI - Geographic Distribution of Radiologists and Utilization of Teleradiology in
Japan: A Longitudinal Analysis Based on National Census Data.
AB - BACKGROUND: Japan has the most CT and MRI scanners per unit population in the
world, and as these technologies spread, their geographic distribution is
becoming equalized. In contrast, the number of radiologists per unit population
in Japan is the lowest among OECD countries and their geographic distribution is
unknown. Likewise, little is known about the use of teleradiology, which can
compensate for the uneven distribution of radiologists. METHODS: Based on the
Survey of Physicians, Dentists and Pharmacists and the Static Survey of Medical
Institutions by the Ministry of Health, Labour and Welfare, a dataset of
radiologists and CT and MRI utilizations in each of Japan's 1811 municipalities
was created. The inter-municipality equity of the number of radiologists was
evaluated using Gini coefficient. Logistic regression analysis, based on Static
Survey data, was performed to evaluate the association between hospital location
and teleradiology use. RESULTS: Between 2006 and 2012 the number of radiologists
increased by 21.7%, but the Gini coefficient remained unchanged. The number of
radiologists per 1,000 CT (MRI) utilizations decreased by 17.9% (1.0%); the
number was highest in metropolis and lowest in town/village and the disparity has
widened from 1.9 to 2.2 (1.6 to 2.0) times. The number of hospitals and clinics
using teleradiology has increased (by 69.6% and 18.1%, respectively). Hospitals
located in towns/villages (odds ratio 1.61; 95% confidence interval 1.26-2.07)
were more likely to use teleradiology than those in metropolises. CONCLUSIONS:
Contrary to the CT and MRI distributions, radiologist distribution has not been
evened out by the increase in their number; in other words, the distribution of
radiologists was not affected by market-derived spatial competition force. As a
consequence, the gap of the radiologist shortage between urban and rural areas is
increasing. Teleradiology, which is one way to ameliorate this gap, should be
encouraged.
PMID- 26421723
TI - Probing Microenvironment in Ionic Liquids by Time-Resolved EPR of Photoexcited
Triplets.
AB - Unusual physicochemical properties of ionic liquids (ILs) open vistas for a
variety of new applications. Herewith, we investigate the influence of
microviscosity and nanostructuring of ILs on spin dynamics of the dissolved
photoexcited molecules. We use two most common ILs [Bmim]PF6 and [Bmim]BF4 (with
its close analogue [C10mim]BF4) as solvents and photoexcited Zn
tetraphenylporphyrin (ZnTPP) as a probe. Time-resolved electron paramagnetic
resonance (TR EPR) is employed to investigate spectra and kinetics of spin
polarized triplet ZnTPP in the temperature range 100-270 K. TR EPR data clearly
indicate the presence of two microenvironments of ZnTPP in frozen ILs at 100-200
K, being manifested in different spectral shapes and different spin relaxation
rates. For one of these microenvironments TR EPR data is quite similar to those
obtained in common frozen organic solvents (toluene, glycerol, N-methyl-2
pyrrolidone). However, the second one favors the remarkably slow relaxation of
spin polarization, being much longer than in the case of common solvents.
Additional experiments using continuous wave EPR and stable nitroxide as a probe
confirmed the formation of heterogeneities upon freezing of ILs and complemented
TR EPR results. Thus, TR EPR of photoexcited triplets can be effectively used for
probing heterogeneities and nanostructuring in frozen ILs. In addition, the
increase of polarization lifetime in frozen ILs is an interesting finding that
might allow investigation of short-lived intermediates inaccessible otherwise.
PMID- 26421722
TI - Agent-Based Model Forecasts Aging of the Population of People Who Inject Drugs in
Metropolitan Chicago and Changing Prevalence of Hepatitis C Infections.
AB - People who inject drugs (PWID) are at high risk for blood-borne pathogens
transmitted during the sharing of contaminated injection equipment, particularly
hepatitis C virus (HCV). HCV prevalence is influenced by a complex interplay of
drug-use behaviors, social networks, and geography, as well as the availability
of interventions, such as needle exchange programs. To adequately address this
complexity in HCV epidemic forecasting, we have developed a computational model,
the Agent-based Pathogen Kinetics model (APK). APK simulates the PWID population
in metropolitan Chicago, including the social interactions that result in HCV
infection. We used multiple empirical data sources on Chicago PWID to build a
spatial distribution of an in silico PWID population and modeled networks among
the PWID by considering the geography of the city and its suburbs. APK was
validated against 2012 empirical data (the latest available) and shown to agree
with network and epidemiological surveys to within 1%. For the period 2010-2020,
APK forecasts a decline in HCV prevalence of 0.8% per year from 44(+/- 2)% to
36(+/- 5)%, although some sub-populations would continue to have relatively high
prevalence, including Non-Hispanic Blacks, 48(+/- 5)%. The rate of decline will
be lowest in Non-Hispanic Whites and we find, in a reversal of historical trends,
that incidence among non-Hispanic Whites would exceed incidence among Non
Hispanic Blacks (0.66 per 100 per years vs 0.17 per 100 person years). APK also
forecasts an increase in PWID mean age from 35(+/- 1) to 40(+/- 2) with a
corresponding increase from 59(+/- 2)% to 80(+/- 6)% in the proportion of the
population >30 years old. Our studies highlight the importance of analyzing
subpopulations in disease predictions, the utility of computer simulation for
analyzing demographic and health trends among PWID and serve as a tool for
guiding intervention and prevention strategies in Chicago, and other major
cities.
PMID- 26421725
TI - A Magnetic Bead-Based Sensor for the Quantification of Multiple Prostate Cancer
Biomarkers.
AB - Novel biomarker assays and upgraded analytical tools are urgently needed to
accurately discriminate benign prostatic hypertrophy (BPH) from prostate cancer
(CaP). To address this unmet clinical need, we report a piezeoelectric/magnetic
bead-based assay to quantitate prostate specific antigen (PSA; free and total),
prostatic acid phosphatase, carbonic anhydrase 1 (CA1), osteonectin, IL-6 soluble
receptor (IL-6sr), and spondin-2. We used the sensor to measure these seven
proteins in serum samples from 120 benign prostate hypertrophy patients and 100
Gleason score 6 and 7 CaP using serum samples previously collected and banked.
The results were analyzed with receiver operator characteristic curve analysis.
There were significant differences between BPH and CaP patients in the PSA, CA1,
and spondin-2 assays. The highest AUC discrimination was achieved with a spondin
2 OR free/total PSA operation--the area under the curve was 0.84 with a p value
below 10(-6). Some of these data seem to contradict previous reports and
highlight the importance of sample selection and proper assay building in the
development of biomarker measurement schemes. This bead-based system offers
important advantages in assay building including low cost, high throughput, and
rapid identification of an optimal matched antibody pair.
PMID- 26421724
TI - Interactions of L-3,5,3'-Triiodothyronine [corrected], Allopregnanolone, and
Ivermectin with the GABAA Receptor: Evidence for Overlapping Intersubunit Binding
Modes.
AB - Structural mechanisms of modulation of gamma-aminobutyric acid (GABA) type A
receptors by neurosteroids and hormones remain unclear. The thyroid hormone L
3,5,3'-triiodothyronine (T3) inhibits GABAA receptors at micromolar
concentrations and has common features with neurosteroids such as
allopregnanolone (ALLOP). Here we use functional experiments on alpha2beta1gamma2
GABAA receptors expressed in Xenopus oocytes to detect competitive interactions
between T3 and an agonist (ivermectin, IVM) with a crystallographically
determined binding site at subunit interfaces in the transmembrane domain of a
homologous receptor (glutamate-gated chloride channel, GluCl). T3 and ALLOP also
show competitive effects, supporting the presence of both a T3 and ALLOP binding
site at one or more subunit interfaces. Molecular dynamics (MD) simulations over
200 ns are used to investigate the dynamics and energetics of T3 in the
identified intersubunit sites. In these simulations, T3 molecules occupying all
intersubunit sites (with the exception of the alpha-beta interface) display
numerous energetically favorable conformations with multiple hydrogen bonding
partners, including previously implicated polar/acidic sidechains and a
structurally conserved deformation in the M1 backbone.
PMID- 26421726
TI - Legacy of Pre-Disturbance Spatial Pattern Determines Early Structural Diversity
following Severe Disturbance in Montane Spruce Forests.
AB - BACKGROUND: Severe canopy-removing disturbances are native to many temperate
forests and radically alter stand structure, but biotic legacies (surviving
elements or patterns) can lend continuity to ecosystem function after such
events. Poorly understood is the degree to which the structural complexity of an
old-growth forest carries over to the next stand. We asked how pre-disturbance
spatial pattern acts as a legacy to influence post-disturbance stand structure,
and how this legacy influences the structural diversity within the early-seral
stand. METHODS: Two stem-mapped one-hectare forest plots in the Czech Republic
experienced a severe bark beetle outbreak, thus providing before-and-after data
on spatial patterns in live and dead trees, crown projections, down logs, and
herb cover. RESULTS: Post-disturbance stands were dominated by an advanced
regeneration layer present before the disturbance. Both major species, Norway
spruce (Picea abies) and rowan (Sorbus aucuparia), were strongly self-aggregated
and also clustered to former canopy trees, pre-disturbance snags, stumps and
logs, suggesting positive overstory to understory neighbourhood effects. Thus,
although the disturbance dramatically reduced the stand's height profile with
~100% mortality of the canopy layer, the spatial structure of post-disturbance
stands still closely reflected the pre-disturbance structure. The former upper
tree layer influenced advanced regeneration through microsite and light
limitation. Under formerly dense canopies, regeneration density was high but
relatively homogeneous in height; while in former small gaps with greater herb
cover, regeneration density was lower but with greater heterogeneity in heights.
CONCLUSION: These findings suggest that pre-disturbance spatial patterns of
forests can persist through severe canopy-removing disturbance, and determine the
spatial structure of the succeeding stand. Such patterns constitute a subtle but
key legacy effect, promoting structural complexity in early-seral forests as well
as variable successional pathways and rates. This influence suggests a continuity
in spatial ecosystem structure that may well persist through multiple forest
generations.
PMID- 26421728
TI - Maintenance Therapy in Colorectal Cancer: Moving the Artillery Down While Keeping
an Eye on the Enemy.
AB - The survival improvement in metastatic colorectal cancer, achieved with more
intensive chemotherapy regimens, has recently led clinicians to question the
optimal duration of therapies and to consider the role of maintenance. Indeed,
patients whose disease is controlled after induction chemotherapy may benefit
from continuing a less intensive regimen in order to reinforce the results
achieved with up-front treatment. In addition, the more favorable toxicity
profile of maintenance approaches would ensure a better quality of life. After
discussing the rationale and the difference of pursuing a maintenance strategy
with chemotherapeutic and/or biologic agents, we present significant available
data from the literature and comment on the current implications and future
directions of maintenance therapy. The current roles of depotentiated treatment
schedules, antiangiogenic compounds, epidermal growth factor receptor inhibitors,
and novel targeted therapies are also reviewed. Finally, we address elements that
may foster clinical and social debate on this topic, suggesting potential aspects
that need to be further investigated.
PMID- 26421727
TI - Acute Biphasic Effects of Ayahuasca.
AB - Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in
syncretic religions in Brazil, is rapidly growing around the world. Because of
this internationalization, a comprehensive understanding of the pharmacological
mechanisms of action of the brew and the neural correlates of the modified states
of consciousness it induces is important. Employing a combination of
electroencephalogram (EEG) recordings and quantification of ayahuasca's compounds
and their metabolites in the systemic circulation we found ayahuasca to induce a
biphasic effect in the brain. This effect was composed of reduced power in the
alpha band (8-13 Hz) after 50 minutes from ingestion of the brew and increased
slow- and fast-gamma power (30-50 and 50-100 Hz, respectively) between 75 and 125
minutes. Alpha power reductions were mostly located at left parieto-occipital
cortex, slow-gamma power increase was observed at left centro-parieto-occipital,
left fronto-temporal and right frontal cortices while fast-gamma increases were
significant at left centro-parieto-occipital, left fronto-temporal, right frontal
and right parieto-occipital cortices. These effects were significantly associated
with circulating levels of ayahuasca's chemical compounds, mostly N,N
dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of
their metabolites. An interpretation based on a cognitive and emotional framework
relevant to the ritual use of ayahuasca, as well as it's potential therapeutic
effects is offered.
PMID- 26421729
TI - Models of the Ni-L and Ni-SIa States of the [NiFe]-Hydrogenase Active Site.
AB - A new class of synthetic models for the active site of [NiFe]-hydrogenases are
described. The Ni(I/II)(SCys)2 and Fe(II)(CN)2CO sites are represented with
(RC5H4)Ni(I/II) and Fe(II)(diphos)(CO) modules, where diphos = 1,2
C2H4(PPh2)2(dppe) or cis-1,2-C2H2(PPh2)2(dppv). The two bridging thiolate ligands
are represented by CH2(CH2S)2(2-) (pdt(2-)), Me2C(CH2S)2(2-) (Me2pdt(2-)), and
(C6H5S)2(2-). The reaction of Fe(pdt)(CO)2(dppe) and [(C5H5)3Ni2]BF4 affords
[(C5H5)Ni(pdt)Fe(dppe)(CO)]BF4 ([1a]BF4). Monocarbonyl [1a]BF4 features an S = 0
Ni(II)Fe(II) center with five-coordinated iron, as proposed for the Ni-SIa state
of the enzyme. One-electron reduction of [1a](+) affords the S = 1/2 derivative
[1a](0), which, according to density functional theory (DFT) calculations and
electron paramagnetic resonance and Mossbauer spectroscopies, is best described
as a Ni(I)Fe(II) compound. The Ni(I)Fe(II) assignment matches that for the Ni-L
state in [NiFe]-hydrogenase, unlike recently reported Ni(II)Fe(I)-based models.
Compound [1a](0) reacts with strong acids to liberate 0.5 equiv of H2 and
regenerate [1a](+), indicating that H2 evolution is catalyzed by [1a](0). DFT
calculations were used to investigate the pathway for H2 evolution and revealed
that the mechanism can proceed through two isomers of [1a](0) that differ in the
stereochemistry of the Fe(dppe)CO center. Calculations suggest that protonation
of [1a](0) (both isomers) affords Ni(III)-H-Fe(II) intermediates, which represent
mimics of the Ni-C state of the enzyme.
PMID- 26421730
TI - Determination of cytotoxicity of traditional Chinese medicine herbs, Rhizoma
coptidis, Radix scutellariae, and Cortex phellodendri, by three methods.
AB - BACKGROUND: Many herbs are used in traditional Chinese medicine TCM) for
treatment of infections but their properties, in particular, their effects on
normal cells have received little attention. This study investigated the
cytotoxic properties of three TCM herbs with potential use in prevention and
treatment of ocular infections, including Acanthamoeba keratitis. METHOD: The
study investigated cytotoxic effects of the herbal extracts of Rhizoma coptidis,
Radix scutellariae, and Cortex phellodendri on human corneal epithelial cells
using trypan blue staining, MTT production, and flow cytometry. Differences
between herbs were determined using repeated measures one-way analysis of
variance, followed by paired t-tests where appropriate. RESULTS: These three
herbs appeared to lack cytotoxicity when tested with trypan blue and MTT, but
flow cytometry revealed that R. coptidis led to cell membrane damage. CONCLUSION:
Lack of cytotoxicity of R. scutellariae and C. phellodendri extracts suggest that
these are potentially suitable for use in ocular preparations. Only flow
cytometry was able to accurately predict cytotoxic effects of extracts of TCM
herbs on HCEC, demonstrating the importance of using a sensitive method of
detection of cytotoxicity.
PMID- 26421731
TI - Opportunities for New Drug Development in Psychiatry: A Glass Half-Full.
PMID- 26421732
TI - Harnessing the Synergistic and Complementary Properties of Fullerene and
Transition-Metal Compounds for Nanomaterial Applications.
PMID- 26421733
TI - Feroxyhyte nanoflakes coupled to up-converting carbon nanodots: a highly active,
magnetically recoverable, Fenton-like photocatalyst in the visible-NIR range.
AB - We demonstrate the enhanced photocatalytic response of a novel Fenton-like
heterogeneous catalyst obtained through the assembly of superparamagnetic
feroxyhyte nanoflakes synthesized by continuous gas-slug microfluidics and carbon
nanodots obtained by pyrolysis from a natural organic source. The novel
nanohybrids enable the utilization of the visible and near-infrared ranges due to
the active role of the carbon nanodots as up-converting photo-sensitizers. This
novel photocatalyst is magnetically recoverable and maintains an excellent
response after multiple reutilization cycles. In addition, its synthesis is based
on inexpensive and abundant raw materials and its photocatalytic response is
evaluated in the presence of energy efficient, affordable light-emitting diodes
(LEDs), thereby providing a promising and feasible alternative to the homogeneous
Fenton process.
PMID- 26421734
TI - Biofilm formation on polystyrene in detached vs. planktonic cells of
polyhydroxyalkanoate-accumulating Halomonas venusta.
AB - Biofilm development is characterized by distinct stages of initial attachment,
microcolony formation and maturation (sessile cells), and final detachment
(dispersal of new, planktonic cells). In this work we examined the influence of
polyhydroxyalkanoate (PHA) accumulation on bacterial surface properties and
biofilm formation on polystyrene in detached vs. planktonic cells of an
environmental strain isolated from microbial mats, Halomonas venusta MAT28. This
strain was cultured either in an artificial biofilm in which the cells were
immobilized on alginate beads (sessile) or as free-swimming (planktonic) cells.
For the two modes of growth, conditions allowing or preventing PHA accumulation
were established. Cells detached from alginate beads and their planktonic
counterparts were used to study cell surface properties and cellular adhesion on
polystyrene. Detached cells showed a slightly higher affinity than planktonic
cells for chloroform (Lewis-acid) and a greater hydrophobicity (affinity for
hexadecane and hexane). Those surface characteristics of the detached cells may
explain their better adhesion on polystyrene compared to planktonic cells.
Adhesion to polystyrene was not significantly different between H. venusta cells
that had accumulated PHA vs. those that did not. These observations suggest that
the surface properties of detached cells clearly differ from those of planktonic
cells and that for at least the first 48 h after detachment from alginate beads
H. venusta retained the capacity of sessile cells to adhere to polystyrene and to
form a biofilm.
PMID- 26421735
TI - Transforming activities of Chlamydia pneumoniae in human mesothelial cells.
AB - Knowledge in viral oncology has made considerable progress in the field of cancer
fight. However, the role of bacteria as mediators of oncogenesis has not yet been
elucidated. As cancer still is the leading cause of death in developed countries,
understanding the long-term effects of bacteria has become of great importance as
a possible means of cancer prevention. This study reports that Chlamydia
pneumoniae infection induces transformation of human mesothelial cells. Mes1
cells infected with C. pneumoniae at a multiplicity of infection of 4 inclusion
forming units/cell showed many intracellular inclusion bodies. After a 7-day
infection an increased proliferative activity was also observed. Real-time PCR
analysis revealed a strong induction of calretinin, Wilms' tumour gene 1,
osteopontin, matrix metalloproteinases-2, and membrane-type 1 metalloproteinases
gene expression in Mes1 cell, infected for a longer period (14 days). The results
were confirmed by western blot analysis. Zymography analysis showed that C.
pneumoniae modulated the in-vitro secretion of MMP-2 in Mes1 cells both at 7 and
14 days. Cell invasion, as measured by matrigel-coated filter, increased after 7
and 14 days infection with C. pneumoniae, compared with uninfected Mes1 cells.
The results of this study suggest that C. pneumoniae infection might support
cellular transformation, thus increasing lung cancer risk.
PMID- 26421736
TI - Impact of formate on the growth and productivity of Clostridium ljungdahlii PETC
and Clostridium carboxidivorans P7 grown on syngas.
AB - The current energy model based on fossil fuels is coming to an end due to the
increase in global energy demand. Biofuels such as ethanol and butanol can be
produced through the syngas fermentation by acetogenic bacteria. The present work
hypothesizes that formate addition would positively impact kinetic parameters for
growth and alcohol production in Clostridium ljungdahlii PETC and Clostridium
carboxidivorans P7 by diminishing the need for reducing equivalents. Fermentation
experiments were conducted using completely anaerobic batch cultures at different
pH values and formate concentrations. PETC cultures were more tolerant to formate
concentrations than P7, specially at pH 5.0 and 6.0. Complete growth inhibition
of PETC occurred at sodium formate concentrations of 30.0 mM; however, no
differences in growth rates were observed at pH 7.0 for the two strains.
Incubation at formate concentrations lower than 2.0 mM resulted in increased
growth rates for both strains. The most recognizable effects of formate addition
on the fermentation products were the increase in the total carbon fixed into
acids and alcohols at pH 5.0 and pH 6.0, as well as, a higher ethanol to total
products ratio at pH 7.0. Taken all together, these results show the ability of
acetogens to use formate diminishing the energy demand for growth, and enhancing
strain productivity.
PMID- 26421737
TI - Stabilization process in Saccharomyces intra and interspecific hybrids in
fermentative conditions.
AB - We evaluated the genetic stabilization of artificial intra- (Saccharomyces
cerevisiae) and interspecific (S. cerevisiae * S. kudriavzevii) hybrids under
wine fermentative conditions. Large-scale transitions in genome size and genome
reorganizations were observed during this process. Interspecific hybrids seem to
need fewer generations to reach genetic stability than intraspecific hybrids. The
largest number of molecular patterns recovered among the derived clones was
observed for intraspecific hybrids, particularly for those obtained by rare
mating. Molecular marker analyses revealed that unstable clones could change
during the industrial process to obtain active dry yeast. When no changes in
molecular markers and ploidy were observed after this process, no changes in
genetic composition were confirmed by comparative genome hybridization,
considering the clone as a stable hybrid. According to our results, under these
conditions, fermentation steps 3 and 5 (30-50 generations) would suffice to
obtain genetically stable interspecific and intraspecific hybrids, respectively.
PMID- 26421738
TI - Comparative microbial ecology of the water column of an extreme acidic pit lake,
Nuestra Senora del Carmen, and the Rio Tinto basin (Iberian Pyrite Belt).
AB - The Iberian Pyrite Belt, located in Southwestern Spain, represents one of the
world's largest accumulations of mine wastes and acid mine drainages. This study
reports the comparative microbial ecology of the water column of Nuestra Senora
del Carmen acid pit lake with the extreme acidic Rio Tinto basin. The canonical
correspondence analysis identified members of the Leptospirillum, Acidiphilium,
Metallibacterium, Acidithiobacillus, Ferrimicrobium and Acidisphaera genera as
the most representative microorganisms of both ecosystems. The presence of
archaeal members is scarce in both systems. Only sequences clustering with the
Thermoplasmata have been retrieved in the bottom layer of Nuestra Senora del
Carmen and one station of Rio Tinto. Although the photosynthetically active
radiation values measured in this lake upper layer were low, they were sufficient
to activate photosynthesis in acidophilic microorganisms. All identified
photosynthetic microorganisms in Nuestra Senora del Carmen (members of the
Chlamydomonas, Zygnemopsis and Klebsormidium genera) are major members of the
photosynthetic eukaryotic community characterized in Rio Tinto basin. This study
demonstrates a close relationship between the microbial diversity of Nuestra
Senora del Carmen pit lake and the diversity detected in the Rio Tinto basin,
which underlain the influence of the shared mineral substrates in the microbial
ecology of these ecosystems.
PMID- 26421739
TI - Ignimbrite textural properties as determinants of endolithic colonization
patterns from hyper-arid Atacama Desert.
AB - This study explores the photosynthetic microbial colonization of rhyolitic
ignimbrites in Lomas de Tilocalar, a hyper-arid region of the Atacama Desert,
Chile. Colonization appeared in the form of a green layer a few millimeters
beneath the ignimbrite surface. Some ignimbrite rocks revealed two distinct
micromorphological areas of identical mineralogical and chemical composition but
different textural properties. According to texture, colonization patterns varied
in terms of the extension and depth of colonization. The diversity of
photosynthetic microorganisms was assessed by denaturing gradient gel
electrophoresis (DGGE) of the 23S rRNA gene and by generating clone libraries of
the 16S rRNA gene. We observed a low diversity of photosynthetic microorganisms
colonizing the ignimbrite microhabitat. Most rRNA gene sequences recovered
greatly resembled those of Chroococcidiopsis hypolith clones from arid deserts.
These results point to highly restrictive conditions of the hyper-arid Atacama
Desert conditioning the diversity of cyanobacteria, and suggest that microbial
colonization and composition patterns might be determined by the microscale
physico-chemical properties of the ignimbrite rocks.
PMID- 26421740
TI - ALLEA Statement on Enhancement of Open Access to Scientific Publications in
Europe.
PMID- 26421741
TI - Small Molecules in the Cone Snail Arsenal.
AB - Cone snails are renowned for producing peptide-based venom, containing
conopeptides and conotoxins, to capture their prey. A novel small-molecule
guanine derivative with unprecedented features, genuanine, was isolated from the
venom of two cone snail species. Genuanine causes paralysis in mice, indicating
that small molecules and not just polypeptides may contribute to the activity of
cone snail venom.
PMID- 26421743
TI - Postpartum duodenal perforation after acute fatty liver of pregnancy.
PMID- 26421742
TI - Submicrometric Films of Surface-Attached Polymer Network with Temperature
Responsive Properties.
AB - Temperature-responsive properties of surface-attached poly(N-isopropylacrylamide)
(PNIPAM) network films with well-controlled chemistry are investigated. The
synthesis consists of cross-linking and grafting preformed ene-reactive polymer
chains through thiol-ene click chemistry. The formation of surface-attached and
cross-linked polymer films has the advantage of being well-controlled without any
caution of no-oxygen atmosphere or addition of initiators. PNIPAM hydrogel films
with same cross-link density are synthesized on a wide range of thickness, from
nanometers to micrometers. The swelling-collapse transition with temperature is
studied by using ellipsometry, neutron reflectivity, and atomic force microscopy
as complementary surface-probing techniques. Sharp and high amplitude temperature
induced phase transition is observed for all submicrometric PNIPAM hydrogel
films. For temperature above LCST, surface-attached PNIPAM hydrogels collapse
similarly but without complete expulsion of water. For temperature below LCST,
the swelling of PNIPAM hydrogels depends on the film thickness. It is shown that
the swelling is strongly affected by the surface attachment for ultrathin films
below ~150 nm. For thicker films above 150 nm (to micrometers), surface-attached
polymer networks with the same cross-link density swell equally. The density
profile of the hydrogel films in the direction normal to the substrate is
confronted with in-plane topography of the free surface. It results that the free
interface width is much larger than the roughness of the hydrogel film,
suggesting pendant chains at the free surface.
PMID- 26421744
TI - Manipulating the kinetics and mechanism of phase separation in dynamically
asymmetric LCST blends by nanoparticles.
AB - The addition of nanoparticles in dynamically asymmetric LCST blends is used to
induce preferred phase-separating morphology by tuning the dynamic asymmetry, and
to control the kinetics of phase separation by slowing down (or even arresting)
the domain growth. For this purpose, we used hydrophobic and hydrophilic fumed
silica, which self-assemble during phase separation into the bulk of the slow (PS
rich) and fast (PVME-rich) dynamic phases, respectively. Both types of
nanoparticles slow down considerably nucleation and growth (NG), spinodal
decomposition (SD), and viscoelastic phase separation (VPS) at volume fractions
as low as 0.5%. Remarkably, beyond a critical volume fraction of hydrophobic
nanosilica thermodynamically controlled phase separation mechanisms (NG and SD)
change to the VPS mechanism due to enhanced dynamic asymmetry. However, in the
presence of hydrophilic nanosilica dynamic asymmetry decreases and beyond a
critical particle volume fraction a transition from the VPS to the SD mechanism
is observed. Phase separation is arrested at 2% nanoparticle loading, and VPS
percolating networks as well as co-continuous SD structures are completely
stabilized by hydrophobic silica or hydrophilic silica, respectively. Electron
microscopy images confirm that double percolated structures are induced in the
presence of 2 vol% of either hydrophobic or hydrophilic nanoparticles.
PMID- 26421745
TI - Analysis of the stability of InGaN/GaN multiquantum wells against ion beam
intermixing.
AB - Ion-induced damage and intermixing was evaluated in InGaN/GaN multi-quantum wells
(MQWs) using 35 keV N(+) implantation at room temperature. In situ ion channeling
measurements show that damage builds up with a similar trend for In and Ga atoms,
with a high threshold for amorphization. The extended defects induced during the
implantation, basal and prismatic stacking faults, are uniformly distributed
across the quantum well structure. Despite the extremely high fluences used (up
to 4 * 10(16) cm(-2)), the InGaN MQWs exhibit a high stability against ion beam
mixing.
PMID- 26421746
TI - Silent Victims: A Brief Report on Abused Older Women in Taiwan.
AB - Around the world, previous research on elder abuse has consistently neglected
abused older women; in many countries, older women often "fall through the
cracks" in elder protection practice as well. This is true in Taiwan, where
traditional cultural concepts cause many older women to suffer as silent victims
of abuse.
PMID- 26421747
TI - A Database of Formation Enthalpies of Nitrogen Species by Compound Methods (CBS
QB3, CBS-APNO, G3, G4).
AB - Accurate thermochemical data for compounds containing C/H/N/O are required to
underpin kinetics simulation and modeling of the reactions of these species in
different environments. There is a dearth of experimental data so computational
quantum chemistry has stepped in to fill this breach and to verify whether
particular experiments are in need of revision. A number of composite model
chemistries (CBS-QB3, CBS-APNO, G3, and G4) are used to compute theoretical
atomization energies and hence enthalpies of formation at 0 and 298.15 K, and
these are benchmarked against the best available compendium of values, the Active
Thermochemical Tables or ATcT. In general the agreement is very good for some 28
species with the only discrepancy being for hydrazine. It is shown that, although
individually the methods do not perform that well, collectively the mean unsigned
error is <1.7 kJ mol(-1); hence, this approach provides a useful tool to screen
published values and validate new experimental results. Using multiple model
chemistries does have some drawbacks but can produce good results even for
challenging molecules like HOON and CN2O2. The results for these smaller
validated molecules are then used as anchors for determining the formation
enthalpies of larger species such as methylated hydrazines and diazenes, five-
and six-membered heterocyclics via carefully chosen isodesmic working reactions
with the aim of resolving some discrepancies in the literature and establishing a
properly validated database. This expanded database could be useful in testing
the performance of computationally less-demanding density function methods with
newer functionals that have the capacity to treat much larger systems than those
tested here.
PMID- 26421748
TI - In Memoriam: Louis J. Guillette, Jr.
PMID- 26421749
TI - Extradyadic Sexual Involvement and Sexual Compulsivity in Male and Female Sexual
Abuse Survivors.
AB - We tested a mediation model in which the relationship between child sexual abuse
(CSA) severity and extradyadic sexual involvement (ESI) is explained through
sexual compulsivity. Participants were 669 adults currently involved in an
intimate relationship who completed self-report questionnaires. Prevalence of ESI
was 32% in women and 57% in men survivors, more than twice the rates among
participants with no CSA history. Sexual compulsivity was significantly higher in
participants with multiple extradyadic partners as compared to participants
reporting only one extradyadic relationship, who nevertheless scored higher than
participants reporting no extradyadic partner. The hypothesized structural
equation model (SEM) was invariant across men and women and indicated CSA
severity was positively and significantly associated with sexual compulsivity,
which, in turn, predicted ESI. However, there was also a direct association
between CSA and ESI. High CSA severity, directly and through high sexual
compulsivity, led to the highest probability of ESI.
PMID- 26421751
TI - OSCE circuit performance effects: Does circuit order influence scores?
AB - It is not uncommon for medical students to raise concerns over the difficulty of
a single station within an Objective Structured Clinical Examination (OSCE),
particularly when they feel they were subject to an unfair situation. Indeed,
test developers also share these concerns about the possibility that a single
extremely difficult station may impact student performance on the station that
follows. As a reaction to the concerns of both students and examiners, we
conducted a study, analyzing the scores of multiple OSCEs. Although our analyses
did not support the complaints of unfairness targeted at the OSCE, we feel it is
a rather enlightening story nevertheless, and one worth sharing.
PMID- 26421752
TI - Antibody Engineering & Therapeutics 2015: The Antibody Society's annual meeting
December 7-10, 2015, San Diego, CA.
AB - Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society,
will be held in San Diego, CA in early December 2015. In this meeting preview,
the chairs provide their thoughts on the importance of their session topics,
which include antibody effector functions, reproducibility of research and
diagnostic antibodies, new developments in antibody-drug conjugates (ADCs),
preclinical and clinical ADC data, new technologies and applications for
bispecific antibodies, antibody therapeutics for non-cancer and orphan
indications, antibodies to harness the cellular immune system, overcoming
resistance to clinical immunotherapy, and building comprehensive IGVH-gene
repertoires through discovering, confirming and cataloging new germline IGVH
genes. The Antibody Society's special session will focus on "Antibodies to watch"
in 2016, which are a subset of the nearly 50 antibodies currently in Phase 3
clinical studies. Featuring over 100 speakers in total, the meeting will commence
with keynote presentations by Erica Ollmann Saphire (The Scripps Research
Institute), Wayne A. Marasco (Dana-Farber Cancer Institute/Harvard Medical
School), Joe W. Gray (Oregon Health & Science University), and Anna M. Wu
(University of California Los Angeles), and it will conclude with workshops on
the promise and challenges of using next-generation sequencing for antibody
discovery and engineering from synthetic and in vivo libraries and on
computational antibody design.
PMID- 26421753
TI - POPs and Pubertal Timing: Evidence of Delayed Development.
PMID- 26421754
TI - Ultra-thin Solid-State Li-Ion Electrolyte Membrane Facilitated by a Self-Healing
Polymer Matrix.
AB - Thin solid membranes are formed by a new strategy, whereby an in situ derived
self-healing polymer matrix that penetrates the void space of an inorganic solid
is created. The concept is applied as a separator in an all-solid-state battery
with an FeS2 -based cathode and achieves tremendous performance for over 200
cycles. Processing in dry conditions represents a paradigm shift for
incorporating high active-material mass loadings into mixed-matrix membranes.
PMID- 26421755
TI - Opioid Use in Hemodialysis Patients.
PMID- 26421756
TI - Phosphorus flows and balances of the European Union Member States.
AB - Global society faces serious "phosphorus challenges" given the scarcity,
essentiality, unequal global distribution and, at the same time, regional excess
of phosphorus (P). Phosphorus flow studies can be used to analyze these
challenges, providing insight into how society (re)uses and loses phosphorus,
identifying potential solutions. Phosphorus flows were analyzed in detail for EU
27 and its Member States. To quantify food system and non-food flows, country
specific data and historical context were considered. The sectors covered were
crop production (CP), animal production (AP), food processing (FP), non-food
production (NF) and consumption (HC). The results show that the EU-27 imported
2392 Gg P in 2005, half of which accumulated in agricultural soils (924 Gg) and
half was lost as waste (1217 Gg). Net accumulation was 4.9 kg P/ha/year ranging
between +23.2 (Belgium) and -2.8 (Slovakia). From the system losses, 54% was lost
from HC in diverse waste flows and 28% from FP, mainly through incinerated
slaughter residues. The largest HC losses (655 Gg) were wastewater (55%), food
waste (27%), and pet excreta (11%). Phosphorus recycling rates were 73% in AP,
29% in FP, 21% in HC and ~0% in NF. The phosphorus use efficiencies showed that,
relative to sector input, about 70% was taken up by crops (CP), 24% was retained
in animals (AP), 52% was contained in food products (FP), 76% was stored in non
food materials (NF), and 21% was recycled (HC). Although wide-ranging variation
between countries, generally phosphorus use in EU-27 was characterized by
relatively (1) large dependency on (primary) imports, (2) long-term accumulation
in agricultural soils, especially in west European countries, (3) leaky losses
throughout entire society, especially emissions to the environment and
sequestered waste, (4) little recycling with the exception of manure, and (5) low
use efficiencies, because of aforementioned issues, providing ample opportunities
for improvement.
PMID- 26421757
TI - Manufacture of Clinical-Grade Human Clonal Mesenchymal Stem Cell Products from
Single Colony Forming Unit-Derived Colonies Based on the Subfractionation
Culturing Method.
AB - Stem cell products derived from mesenchymal stem cells (MSCs) have been widely
used in clinical trials, and a few products have been already commercialized.
However, the therapeutic effects of clinical-grade MSCs are still controversial
owing to mixed results from recent clinical trials. A potential solution to
overcome this hurdle may be to use clonal stem cells as the starting cell
material to increase the homogeneity of the final stem cell products. We have
previously developed an alternative isolation and culture protocol for
establishing a population of clonal MSCs (cMSCs) from single colony forming unit
(CFU)-derived colonies. In this study, we established a good manufacturing
practice (GMP)-compatible procedure for the clinical-grade production of human
bone marrow-derived cMSCs based on the subfractionation culturing method. We
optimized the culture procedures to expand and obtain a clonal population of
final MSC products from single CFU-derived colonies in a GMP facility. The
characterization results of the final cMSC products met our preset criteria.
Animal toxicity tests were performed in a good laboratory practice facility, and
showed no toxicity or tumor formation in vivo. These tests include single
injection toxicity, multiple injection toxicity, biodistribution analysis, and
tumorigenicity tests in vivo. No chromosomal abnormalities were detected by in
situ karyotyping using oligo-fluorescence in situ hydridization (oligo-FISH),
providing evidence of genetic stability of the clinical-grade cMSC products. The
manufacture and quality control results indicated that our GMP methodology could
produce sufficient clonal population of MSC products from a small amount of bone
marrow aspirate to treat a number of patients.
PMID- 26421758
TI - Comparison of Over-the-Rail and Rail Yard Measurements of Diesel Locomotives.
AB - Locomotive prime mover engine emission rates are typically measured at steady
state for discrete throttle notches using an engine dynamometer weighted by a
standard duty cycle. However, this method may not represent real-world locomotive
emissions. A method for in-use measurement of passenger locomotives, using a
portable emissions measurement system (PEMS), was developed to estimate duty
cycle average emission rates. We conducted 48 measurements of one-way trips
between Raleigh and Charlotte, NC, on 7 locomotives and 18 sets of measurements
in the rail yard (RY). Real-world duty cycles differed from those used for
regulatory analyses, leading to statistically significant lower cycle average NOx
and HC emission rates. Compared to RY measurements, notch average NOx emission
rates measured over-the-rail (OTR) at the highest two notch settings were, on
average, 19% lower for four locomotives. At the highest notch, OTR CO2 emission
rates were, on average, 12% lower than RY rates for five locomotives. For a more
accurate representation of real-world emission rates, OTR measurements are
preferred. However, using steady-state notch average RY emission rates and
standard duty cycles may be tolerable for some applications. OTR versus RY cycle
average emission rates typically differed by less than 10%.
PMID- 26421760
TI - Potatoes - A crop resistant against input of heavy metals from the metallicaly
contaminated soil.
AB - The objective of our study was to assess the extent of accumulation of cadmium,
lead and zinc in potato tubers depending on the concentration of these heavy
metals in soil and to evaluate the resistance of 11 cultivars of potato
cultivated in 5 localities of the Slovakia against input of these heavy metals
into the consumption part of potato. Contents of Cd (Pb, Zn) in soil were 0.94
2.54 (18.03-24.90, 35.71-72.40) mg/kg in soil extract by aqua regia and 0.030
0.188 (0.149-0.356, 0.052-0.238) mg/kg in soil extract by NH4NO3. The contents of
Cd, Pb, and Zn were determined in potatoes in extracts of freeze-dried samples
and expressed in mg/kg of fresh matter (FM). Determined contents of heavy metals
were in the range of ND-0.058 mg Cd/kg FM, 0.020-0.630 mg Pb/kg FM, 1.836-3.457
mg Zn/kg FM, resp. The statistically significant correlation between heavy metal
content in soil and its content in potato tubers were confirmed only: cv. Laura -
Spissky Stvrtok (Cd), cv. Red Anna - Odorin (Pb) and Marabel, Red Anna - Odorin,
cv. Marabel - Belusa, cv. Volumia - Imel (Zn).
PMID- 26421759
TI - Combinatorial Motor Training Results in Functional Reorganization of Remaining
Motor Cortex after Controlled Cortical Impact in Rats.
AB - Cortical reorganization subsequent to post-stroke motor rehabilitative training
(RT) has been extensively examined in animal models and humans. However, similar
studies focused on the effects of motor training after traumatic brain injury
(TBI) are lacking. We previously reported that after a moderate/severe TBI in
adult male rats, functional improvements in forelimb use were accomplished only
with a combination of skilled forelimb reach training and aerobic exercise, with
or without nonimpaired forelimb constraint. Thus, the current study was designed
to examine the relationship between functional motor cortical map reorganization
after experimental TBI and the behavioral improvements resulting from this
combinatorial rehabilitative regime. Adult male rats were trained to proficiency
on a skilled reaching task, received a unilateral controlled cortical impact
(CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post
CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control
procedures (n = 13). The RT group participated in daily skilled reach training,
voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen
significantly improved impaired forelimb reaching success and normalized reaching
strategies, consistent with previous findings. RT also enlarged the area of motor
cortical wrist representation, derived by intracortical microstimulation,
compared to NoRT. These findings indicate that sufficient RT can greatly improve
motor function and improve the functional integrity of remaining motor cortex
after a moderate/severe CCI. When compared with findings from stroke models,
these findings also suggest that more intense RT may be needed to improve motor
function and remodel the injured cortex after TBI.
PMID- 26421761
TI - Ebola Virus Disease in Health Care Workers--Guinea, 2014.
AB - An outbreak of Ebola virus disease (Ebola) began in Guinea in December 2013 and
has continued through September 2015. Health care workers (HCWs) in West Africa
are at high risk for Ebola infection owing to lack of appropriate triage
procedures, insufficient equipment, and inadequate infection control practices.
To characterize recent epidemiology of Ebola infections among HCWs in Guinea,
national Viral Hemorrhagic Fever (VHF) surveillance data were analyzed for HCW
cases reported during January 1-December 31, 2014. During 2014, a total of 162
(7.9%) of 2,210 laboratory-confirmed or probable Ebola cases among Guinean adults
aged >=15 years occurred among HCWs, resulting in an incidence of Ebola infection
among HCWs 42.2 times higher than among non-HCWs. The disproportionate burden of
Ebola infection among HCWs taxes an already stressed health infrastructure,
underscoring the need for increased understanding of transmission among HCWs and
improved infection prevention and control measures to prevent Ebola infection
among HCWs.
PMID- 26421762
TI - Contents of constituents and antioxidant activity of seed and pulp extracts of
Annona coriacea and Annona sylvatica.
AB - The antioxidant potential of fruit pulp and seeds of extracts of the Annona
coriacea, and A. sylvatica (Annonaceae) were investigated, as well contents total
phenolics, flavonoids, condensed tannins and ascorbic acid. Was used to determine
the antioxidant activity the 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH),
beta-carotene bleaching and ABTS radical cation method. The total phenol, total
flavonoid, condensed tannin, and ascorbic acid contents were measured
spectrophotometrically. In this study, the pulp and seeds of the fruits were
extracted using methanol/water (8:2) for maceration. The seed extracts of A.
coriacea demonstrated a moderate antioxidant effect with free radical scavenging
activity of 31.53%, by the DPPH test, 51.59% by the beta-carotene bleaching test
and 159.50 uM trolx/g of extract in the ABTS assay. We found that the
hydromethanolic seed extract of A. coriacea had high total phenol (147.08 +/-
4.20 mg of GAE/g of extract) and flavonoid (131.18 +/- 2.31 mg of QE/g of
extract) content. This indicated that the antioxidant activity of the extracts
was related to the contents of these constituents.
PMID- 26421763
TI - Gastrointestinal parasites of maned wolf (Chrysocyon brachyurus, Illiger 1815) in
a suburban area in southeastern Brazil.
AB - We examined 42 maned wolf scats in an unprotected and disturbed area of Cerrado
in southeastern Brazil. We identified six helminth endoparasite taxa, being
Phylum Acantocephala and Family Trichuridae the most prevalent. The high
prevalence of the Family Ancylostomatidae indicates a possible transmission via
domestic dogs, which are abundant in the study area. Nevertheless, our results
indicate that the endoparasite species found are not different from those
observed in protected or least disturbed areas, suggesting a high resilience of
maned wolf and their parasites to human impacts, or a common scenario of disease
transmission from domestic dogs to wild canid whether in protected or unprotected
areas of southeastern Brazil.
PMID- 26421764
TI - Vertical stratification and effect of petiole and dry leaf size on arthropod
feeding guilds in Cecropia pachystachya (Urticaceae).
AB - This study aimed to test for vertical stratification and the effects of dry leaf
size on herbivore and predator arthropods and petiole length on insect borers in
Cecropia pachystachya. The leaves were sampled in three strata: attached to the
plant, suspended on the vegetation and on the ground. We detected vertical
stratification only in the guild of predator arthropods associated with dry
leaves, with lower richness and abundance in the attached stratum. In addition,
larger leaves positively affected the insect herbivore fauna, whereas the
richness and abundance of insect borers increased with petiole length. The
greater isolation of leaves attached to trees relative to the surrounding
vegetation likely creates greater difficulty for dispersal and colonization by
non-winged predators such as spiders. Larger dry leaves provide more shelter
against predators and climate variations for insect herbivores. Moreover, larger
petioles increase the availability of resources and nesting sites for insect
borers. These results are consistent with other studies that found a similarity
in the structure of feeding guilds across vertical strata and with studies that
showed an increase in species richness and abundance of free-feeding insect
herbivores with increasing structural complexity of their host.
PMID- 26421765
TI - Jaguar (Panthera onca Linnaeus, 1758) roadkill in Brazilian Atlantic Forest and
implications for species conservation.
AB - We report the roadkill of a jaguar in one of the longest highways in Brazil (BR
101), in the stretch where this road crosses one of the most important Atlantic
Forest remnants in the country: the Linhares-Sooretama block. The jaguar
population present in this area represents the very last in entire Espirito Santo
state. There is an approved project to the lines duplication of the entire BR-101
Highway and the company responsible by the work has already started the first
activities in the state. However, there is no environmental impact assessment
already done neither planning for the implementation of measures to avoid or
reduce the roadkill risk in the region. Thus, to minimize the impacts associated
with the BR-101, we do not recommend its lines duplication along the 15 km
stretch traversing the Linhares-Sooretama block. In addition, alternatively, we
suggest the deviation of the current route of the BR-101 Highway or the
construction of overpasses to fauna in the most critical points, interspersing
these overpasses with electronic speed monitoring devices and warning and
educational plates.
PMID- 26421766
TI - Jaw musculature of Cyclarhis gujanensis (Aves: Vireonidae).
AB - Cyclarhis gujanensis is a little bird which feeds on high number of large preys,
such frogs, lizards, snakes, bats and birds. As there are few studies on the
cranial anatomy of this species, we aimed to describe the cranial myology to
contribute to the anatomical knowledge of this species and to make some
assumptions about functional anatomy. Thus, we described the muscles from the jaw
apparatus (external and internal adductor muscles, the muscles of the pterygoid
system and the depressor muscles of the mandible). The adductor system is the
greatest and multipinulated, particularly in its origin in the caudal portion of
the temporal fossa. The depressor jaw muscles systems are enlarged with many
components in complexity. The most of jaw apparatus muscles are short, but the
strength (biting or crushing forces) from short feeding apparatus fibers probably
is increased by high number of components and pinnulation. These anatomical
aspects of the muscles indicate a considerable force in the jaws, without which
C. gujanensis probably could not cut their prey into smaller pieces. However,
functional approaches to analysis of forces of the muscle fibers are needed to
corroborate / refute the hypotheses mentioned above.
PMID- 26421767
TI - Feather mites (Acari, Astigmata) associated with birds in an Atlantic Forest
fragment in Northeastern Brazil.
AB - The present study reports associations between feather mites (Astigmata) and
birds in an Atlantic Forest fragment in Rio Grande do Norte state, in Brazil. In
the laboratory, mites were collected through visual examination of freshly killed
birds. Overall, 172 individuals from 38 bird species were examined, between
October 2011 and July 2012. The prevalence of feather mites was 80.8%,
corresponding to 139 infested individuals distributed into 30 species and 15
families of hosts. Fifteen feather mite taxa could be identified to the species
level, sixteen to the genus level and three to the subfamily level, distributed
into the families Analgidae, Proctophyllodidae, Psoroptoididae, Pteronyssidae,
Xolalgidae, Trouessartiidae, Falculiferidae and Gabuciniidae. Hitherto unknown
associations between feather mites and birds were recorded for eleven taxa
identified to the species level, and nine taxa were recorded for the first time
in Brazil. The number of new geographic records, as well as the hitherto unknown
mite-host associations, supports the high estimates of diversity for feather
mites of Brazil and show the need for research to increase knowledge of plumicole
mites in the Neotropical region.
PMID- 26421768
TI - Growth of Paecilomyces variotii in B0 (diesel), B100 (biodiesel) and B7 (blend),
degradation and molecular detection.
AB - The introduction of biodiesel to diesel may allow the fuel to be more susceptible
to microorganism growth, especially during incorrect storage. To evaluate the
effect of adding biodiesel in pure diesel on the growth of Paecilomyces variotii,
microcosms containing pure diesel (B0), blend diesel/biodiesel (B7) and pure
biodiesel (B100) were used. In microcosm with minimal mineral medium and B0, B7
or B100, after 60 days, the biomass (dry weight) formed at interface oil-water in
B7 and B100 was significantly higher when compared to that of B0. Infrared
analysis showed reduction of the carbonile fraction in B7 and B100 suggesting
formation of intermediate compounds in B7. To monitor possible contamination of
fuel storage tank by P. variotii samples were collected and analysed by specific
PCR assay for detection of P. variotii spores in the aqueous phase. This method
was able to detect a minimum of 103 spores ml-1, corresponding to 0.0144 ng ul-1
of DNA. Specificity was tested against Aspergillus fumigatus and Pseudallescheria
boydii.
PMID- 26421770
TI - Variations of Salminus hilarii diet (Ostariophysi, Characidae): seasonal and
ontogenetic effects.
AB - This study described the variations seasonal and ontogenetic of Salminus hilarii
diet. Samples were collected in the Sorocaba River, Sao Paulo, Brazil, one of the
few rivers where individuals of the species still occur in a higher frequency.
The preys consumed were analyzed by Importance Alimentary Index (AIi). To
determine similarities between year seasons, the AIi data were analyzed by the
Morisita-Horn index and reduced in cluster analysis, along with a statistical
comparison made by one-way ANOSIM test (5%). The feeding activity was analyzed
according to the stomach repletion index and compared among the year seasons
using non parametric variance analysis Kruskal-Wallis test (5%). Comparison of
prey consumed between immature and adult individuals was made by Spearman
correlation (5%). A Pearson correlation (5%) was applied between the standard
length of the fish and prey consumed, as well as between the mouth and prey
heights. The analyzes of stomach contents showed that the diet of this species
was exclusively piscivorous, with significant difference of prey consumption
during the period, the same happening among adult and immature individuals. It
was observed that these fishes use to swallow their prey whole and that
significant correlations between size of predator and prey size can be observed.
There is also correlation between the mouth height and the maximum prey depth.
Salminus hilarii feeds on the available prey, and the species food composition
and feeding activity depends on prey's abundance, their size and morphology, as
do the water temperatures.
PMID- 26421769
TI - The hyporheic zone and its functions: revision and research status in Neotropical
regions.
AB - The hyporheic zone (HZ), as the connecting ecotone between surface- and
groundwater, is functionally part of both fluvial and groundwater ecosystems. Its
hydrological, chemical, biological and metabolic features are specific of this
zone, not belonging truly neither to surface- nor to groundwater. Exchanges of
water, nutrients, and organic matter occur in response to variations in discharge
and bed topography and porosity. Dynamic gradients exist at all scales and vary
temporally. Across all scales, the functional significance of the HZ relates to
its activity and connection with the surface stream. The HZ is a relatively rich
environment and almost all invertebrate groups have colonized this habitat. This
fauna, so-called hyporheos, is composed of species typical from interstitial
environment, and also of benthic epigean and phreatic species. The hyporheic
microbiocenose consists in bacteria, archaea, protozoa and fungi. The HZ provides
several ecosystem services, playing a pivotal role in mediating exchange
processes, including both matter and energy, between surface and subterranean
ecosystems, functioning as regulator of water flow, benthic invertebrates refuge
and place of storage, source and transformation of organic matter. The hyporheic
zone is one of the most threatened aquatic environments, being strongly
influenced by human activities, and the least protected by legislation worldwide.
Its maintenance and conservation is compelling in order to preserve the
ecological interconnectivity among the three spatial dimensions of the aquatic
environment. Although several researchers addressed the importance of the
hyporheic zone early, and most contemporary stream ecosystem models explicitly
include it, very little is known about the HZ of Neotropical regions. From a
biological standpoint, hyporheos fauna in Neotropical regions are still largely
underestimated. This review focuses on a brief presentation of the hyporheic zone
and its functions and significance as an ecotone. We also highlighted the key
aspects considering also the current status of research in Neotropical regions.
PMID- 26421771
TI - Impacts of artificial reservoirs on floristic diversity and plant functional
traits in dry forests after 15 years.
AB - Dams are of paramount importance to a wide variety of human services and many of
their environmental problems are known; however, there are few studies in the
world addressing the impacts on the native vegetation previously distant from
water bodies which became close to the lakeshore created by a dam. Thus, this
paper aims to analyze the responses of a dry forest to a dam after 15 years. For
this, 20 random samples of 40 trees were made, 10 close to the lakeshore and 10
distant from it, by applying the central square point method. Close to the dam,
we found higher values regarding basal area, number of trees, number of evergreen
trees, and zoochoric syndrome, but there were lower values of Shannon's diversity
index. Therefore, the impacts of the dam after 15 years caused several changes to
the tree community. The greater basal area close to the dam suggests that water
deficit during the dry season was decreased and plants have thicker trunks. On
the other hand, this sector had much more zoochoric syndrome and a larger number
of evergreen trees than plots which are distant from water, suggesting changes
with regard to the community's ecological functions. Furthermore, structural
floristic data shows that the sector close to the dam is less similar to other
deciduous forests within the same geographical region than the sector distant
from water, thus providing evidence of the impacts of dams on the tree community.
PMID- 26421772
TI - Does the habitat structure control the distribution and diversity of the
Odonatofauna?
AB - The statement that the habitat complexity and structure govern the abundance and
diversity of biological communities has been widely investigated. In this
context, we assumed the hypothesis of habitat heterogeneity, that is, the higher
habitat complexity leads to greater diversity of Odonata. In addition, we
analyzed the influence of habitat structure on the distribution of this
community, and evaluated the effects of abiotic variables. Odonata larvae were
collected with sieves and by electrofishing in ten neotropical streams belonging
to the Pirapo River basin. Forty species of Odonata were registered, which were
distributed in eight families, Libellulidae stood out with the highest richness.
The high gamma diversity and distribution of Odonata were associated with habitat
heterogeneity in these streams. However, the abiotic variables also seem to
affect the distribution of Odonata species, in view of the impact of the land use
in the vicinity of streams.
PMID- 26421773
TI - First record of Hysterothylacium sp. Moravec, Kohn et Fernandes, 1993 larvae
(Nematoda: Anisakidae) infecting the ornamental fish Hyphessobrycon eques
Steindachner, 1882 (Characiformes, Characidae).
AB - This study reports for the first time infection with Hysterothylacium sp. larvae
in the ornamental fish Hyphessobrycon eques from the Paranapanema River,
Jurumirim Reservoir, Sao Paulo State, Brazil. A sample of 33 specimens of H.
eques was collected in October, 2011. Four specimens of H. eques were parasitized
by Hysterothylacium sp. larvae in the intestine and coelomic cavity, with
prevalence of 12.1%, mean intensity of infection of 1, and mean abundance of
0.121 +/- 0.05. A total of 40 unidentified free-living nematodes were found in
the stomach content of 17 fish. This fish species is introduced in the
Paranapanema River. Invasive species may affect the native fauna given the
introduction of pathogens and parasites. This study also complements data on the
diet of H. eques due to the records of free-living nematode as part of the
stomach content. Infections with Hysterothylacium sp. larvae may affect the
biology of this fish and bring about profit losses to aquarists.
PMID- 26421774
TI - The effects of rainfall and vegetation on litterfall production in the semiarid
region of northeastern Brazil.
AB - Litterfall has a strong influence on biodiversity and on the chemical and
physical characteristics of the soil. Its production can be quite variable over
time and space, and can be influenced by both natural and anthropogenic factors.
We evaluated litterfall production and its relationship with rainfall, species
richness, and the densities of the arboreal vegetation. Thirty litter traps were
constructed with 1.0 m2 nylon mesh (1.0 mm) and randomly installed within a 2000
m * 500 m area of arboreal/shrub Caatinga (dryland) vegetation. Litter samples
were collected monthly from November/2010 to June/2012, and the collected
material was classified, dried, and weighted. Species richness and tree densities
were determined by conducting phytosociological surveys in 20 m * 20 m plots
surrounding each of the litter traps. The litterfall accumulation rate was 3.673
Mgha-1yr-1, similar to values from other seasonally dry tropical forests.
Litterfall production was continuous, and principally accompanied the rainfall
rate, but with a time interval of 2 to 3 months, with the greatest accumulation
at the beginning of the dry season and the least during the rainy season. The
different fractions of materials demonstrated distinct accumulation rates, with
leaves being the principal category. Litterfall production was found to be
related to tree density, but no link was found to species richness. The observed
temporal heterogeneity of litterfall production demonstrated a strong link
between rainfall and the dynamics of nutrient cycling in the semiarid region of
Brazil.
PMID- 26421775
TI - Nursing Home Registered Nurses' and Licensed Practical Nurses' Knowledge of
Causes of Falls.
AB - Reducing falls in nursing homes requires a knowledgeable nursing workforce. To
test knowledge, 8 validated vignettes representing multifactorial fall causes
were administered to 47 nurses from 3 nursing homes. Although licensed practical
nurses scored higher than registered nurses in individual categories of falls,
when we computed the average score of all 8 categories between groups of
registered nurses and licensed practical nurses, registered nurses scored higher
(F = 4.106; P < .05) in identifying 8 causal reasons for older adults to fall.
PMID- 26421776
TI - Global Mental Health: What is Your Role in This Movement?
PMID- 26421777
TI - The Future of the Portuguese Health System.
PMID- 26421778
TI - [Regulation of Parental Leave Among Parents of Very Preterm Infants].
PMID- 26421780
TI - Clinical and Radiological Characterization of Progressive Multifocal
Leukoencephalopathy in HIV-Infected Patients: A Retrospective Analysis and Review
of the Literature.
AB - INTRODUCTION: Progressive multifocal leukoencephalopathy is a demyelinating
disease of the central nervous system caused by John Cunningham virus, mostly
associated with immunodeficiency conditions, such as the human immunodeficiency
virus infection. Progressive multifocal leukoencephalopathy can have multiple
clinical features and usually presents a typical lesion pattern on brain magnetic
resonance imaging. Its course may be rapidly progressive, although immunological
responsiveness can be associated with an improved prognosis. MATERIAL AND
METHODS: We performed a retrospective analysis of the clinical and radiological
data from patients admitted in our institution between January 2005 and April
2014 with the diagnosis of definitive progressive multifocal leukoencephalopathy
(ICD10:A81.2) in the setting of human immunodeficiency virus infection. RESULTS:
Twenty-one patients were included in our study, mostly men (n = 20, 95.2%). Mean
age at diagnosis was 39 years. Motor deficits were the most common clinical
finding. John Cunningham virus-DNA was detected in the cerebral spinal fluid in
20 patients (95.2%). Brain imaging studies most commonly disclosed bilateral
supratentorial, asymmetric lesions. Four (19%) patients developed immune
reconstitution inflammatory syndrome in the follow-up. Therapeutic approach
included initiation and continuation/optimization of antiretroviral therapy, with
adjunctive therapy with corticosteroids in four patients. Seventeen (81%)
patients died during the study period; median survival time following progressive
multifocal leukoencephalopathy diagnosis was 3 months (range 1 - 13). DISCUSSION:
The results of our study are in accordance with the data previously published on
progressive multifocal leukoencephalopathy in human immunodeficiency virus
patients. Progressive multifocal leukoencephalopathy is predominantly associated
with severe immunosuppression, particularly in patients who are not under anti
retroviral therapy, and usually presents with motor and cognitive symptoms and
signs. A typical bilateral asymmetric pattern in conventional magnetic resonance
imaging is present in the majority of the patients. There is no specific therapy
for progressive multifocal leukoencephalopathy and it is usually fatal, although
outcomes can improve with highly active anti-retroviral therapy. Immune
reconstitution inflammatory syndrome is also an important complication related
with progressive multifocal leukoencephalopathy, usually associated with anti
retroviral therapy. Progressive multifocal leukoencephalopathy-immune
reconstitution inflammatory syndrome presents with different imaging
characteristics from progressive multifocal leukoencephalopathy and treatment
with steroids can improve survival. CONCLUSION: The mortality rate and long-term
neurological morbidity associated with progressive multifocal leukoencephalopathy
are quite high. These data should increase clinician awareness to the occurrence
of progressive multifocal leukoencephalopathy among human immunodeficiency virus
patients and highlight the important role of magnetic resonance imaging, as early
diagnosis may beassociated with better outcome.
PMID- 26421779
TI - [Analysis of the Cochrane Review: Angiotensin Converging Enzyme Inhibitors Versus
Angiotensin Receptor Blockers for Primary Hypertension. Cochrane Database Syst
Rev. 2014,8: CD009096].
AB - Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are
first line drugs in the treatment of hypertension. The aim of this review was to
assess if there are differences between these drug classes regarding the
prevention of total mortality, occurrence of cardiovascular events and of adverse
effects. A systematic review and metanalysis was performed, searching for studies
that compare angiotensin converting enzyme inhibitors and angiotensin receptor
blockers face-to-face, in several databases until July 2014. The study selection
and data extraction were performed by 2 independent researchers. Nine studies
were included, with a total of 10 963 participants, 9 398 of which participated
in the same study and had high cardiovascular risk. No differences were observed
regarding total mortality, cardiovascular mortality or total cardiovascular
events. A slightly smaller risk was observed with angiotensin receptor blockers
regarding withdrawal due to adverse effects (55 people were needed to be treated
with angiotensin receptor blockers for 4.1 years to avoid one withdrawal due to
adverse effect), mainly due to the occurrence of dry cough with angiotensin
converting enzyme inhibitors. Thus, no differences were observed between
angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the
prevention of total mortality and cardiovascular events, and angiotensin receptor
blockers were better tolerated. Given the large proportion of participants with a
high cardiovascular risk, the generalization of these results to other
populations is limited.
PMID- 26421781
TI - Off-Label and Unlicensed Drug Use in Neonatology: Reality in a Portuguese
University Hospital.
AB - INTRODUCTION: This study aims to characterize the drugs used in a Portuguese
Neonatal Intensive Unit Care, assess the rate of off-label or unlicensed drugs
use according to the information available in the Summary of Product
Characteristics and compare results between preterm and full-term neonates.
MATERIAL AND METHODS: A 6-month period retrospective cross-sectional study was
conducted in our Neonatal Intensive Unit Care in 2013. Prescribed drugs data were
recorded and compared with the paediatric information contained in drugs Summary
of Product Characteristics. RESULTS: We analyzed 1011 prescriptions of 84 active
substances, made in 218 admissions. In 42.9% of the cases, medicines were used
according to Summary of Product Characteristics information; 27.9% of drugs were
approved for neonatal period but used in an off-label manner; off-label drugs for
neonates were used in 10.1%, whereas those with undetermined approval state and
contraindicated were used 6.0% and 8.7% of the cases, respectively. Unlicensed
prescriptions accounted for 4.4% of total. Preterm received a higher rate of
drugs used according to Summary of Product Characteristics (p < 0.0001), whereas
full-term received more off-label drugs for dose/frequency (p < 0.0001) and
contra-indicated for neonates (p < 0.012). DISCUSSION: Preterm neonates received
a higher median number of drugs, since they stayed longer in the unit. The main
reason for off-label prescribing was the use of doses/frequencies of
administration different from those stated in the Summary of Product
Characteristics, suggesting that updating these documents is necessary.
Manipulation of medicines is one of the causes for unlicensed drugs use,
emphasizing the lack of appropriate formulations for neonatal age. CONCLUSION:
Progresses have been made to reduce the risks of off-label/unlicensed
prescriptions, but competent authorities must continue their efforts to develop
safer and more effective drugs for neonatal period.
PMID- 26421782
TI - The Role of Haemoglobin A1c in Screening Obese Children and Adolescents for
Glucose Intolerance and Type 2 Diabetes.
AB - INTRODUCTION: In 2012, an international expert committee in diabetes wrote in
favor of screening adult and paediatric patients for glucose intolerance and type
2 diabetes using glycated haemoglobin. The aim of this study was to evaluate
glycated haemoglobin utility as a screening tool in a young obese mainly
Caucasian population. MATERIAL AND METHODS: Children [(n = 266), body mass index
z-score 3.35 +/- 0.59, 90% Caucasian 90%, 55% female, median age 12.3 (range: 8.9
- 17.6) years old] recently referred to a tertiary hospital-based obesity clinic
underwent a routine oral glicose tolerance test and glycated haemoglobin
measurement. EXCLUSION CRITERIA: abnormal forms of haemoglobin and conditions
linked to increased erythrocyte turnover. RESULTS: The oral glicose tolerance
test diagnosed 13 (4.9%) subjects as prediabetic but none as diabetic. According
to glycated haemoglobin, 32 would be prediabetic (29 false positives) and one
would be diabetic (when he was only glucose intolerant). On the other hand, 10
prediabetic patients would not have been identified (false negatives). Glycated
haemoglobin receiver operator characteristic analysis area under the curve was
0.59 (CI 95% 0.40 - 0.78), confirming its reduced capacity to identify
prediabetes. Better results were achieved when calculating receiver operator
characteristic analysis area under the curve for fasting glucose (0.76;CI 95%
0.66 - 0.87), homeostasis model assessment for insulin resistance (0.77; CI 95%
0.64 - 0.90) and triglycerides:HDL cholesterol ratio (0.81; CI 95% 0.66 - 0.96).
DISCUSSION: In Paediatric populations, especially when mainly Caucasian, glycated
haemoglobin does not seem to be a useful screening tool for prediabetes.
CONCLUSION: For this reason, it would appear premature to advise it as a
diagnostic tool until significantly more data is available. Homeostasis model
assessment for insulin resistance and triglycerides: HDL cholesterol have higher
precision and can be calculated using a fasting blood sample.
PMID- 26421783
TI - Cephalometric Evaluation of Children with Allergic Rhinitis and Mouth Breathing.
AB - INTRODUCTION: Orthodontists frequently treat children with mouth breathing. The
purpose of the present study was to examine dental positions, skeletal effects
and the pharyngeal airway space of children with chronic allergic rhinitis, when
compared with a control group exhibiting a normal breathing pattern. MATERIAL AND
METHODS: Seventy Caucasian children from Santa Maria University Hospital - North
Lisbon Hospital Center were evaluated, between September 2009 and February 2013.
The study group comprised of 35 children with chronic allergic rhinitis, both
genders, aged 5 - 14, with positive reaction to allergens, mouth breathing and
malocclusion. The control group was composed of 35 children, both genders,
displaying normal nasal breathing and malocclusion, who resorted to the
orthodontic department. Measures of Ricketts, Steiner and McNamara's analysis
were used and the t- Student test was applied to the data obtained. RESULTS:
Statistically significant differences were observed between the oral and nasal
breathers, respectively: lower facial height (49.1/45.9 mm), Frankfurt a
mandibular plane angle (30.1/26.9o) and Sela-Nasion - oclusal plane angle
(17.3/15o), maxillary length (78.4/82.4 mm), mandibular length (102.4/107 mm),
overbite (0.8/3.1mm) and overjet (4/4.7 mm). DISCUSSION: Comparison between the
allergic rhinitis and control group showed that there is an increased lower
facial height, larger Frankfurt a mandibular plane angle and Sela-Nasion oclusal
plane angle in children with chronic allergic rhinitis. This group also had a
shorter maxillary and mandibular length, less overbite and decreased upper airway
space. CONCLUSIONS: Children with allergic rhinitis and mouth breathing have
longer faces, shorter maxillas and mandibles and a narrowed pharyngeal airway
space. No statistical differences between the groups in sagital relationships or
in dental inclinations were found.
PMID- 26421784
TI - Parathyroid Hormone as a Predictor of Post-Thyroidectomy Hipocalcemia: A
Prospective Evaluation of 100 Patients.
AB - INTRODUCTION: Hypocalcemia is a frequent complication after total thyroidectomy
and the main reason for prolonged hospitalization of these patients. MATERIAL AND
METHODS: We studied prospectively 112 patients who underwent total or
completation thyroidectomy between June 2012 and November 2013. Twelve patients
with preoperative changes in parathyroid function were excluded. Parathyroid
hormone and calcium levels were determined pre-operatively, immediately after
surgery, on 1st day and on 14th day after surgery. RESULTS: Of the 100 patients
enrolled, 60 have developed hypocalcaemia (60%) but only 14 patients had
symptomatic hypocalcaemia. It mostly occurs 24 hours after surgery (76.7%). It
was permanent in 3 patients and temporary in the others. In the 60 patients with
hypocalcaemia, it has been found hypoparathyroidism in 19 patients immediately
after surgery, in 14 patients on 1st day but only 3 had hypoparathyroidism
(patients with permanent hypocalcaemia). Comparing the group of patients with and
without hypocalcaemia we found a decrease of parathyroid hormone in both
(immediately after surgery and on 1st day) but was more important in the
hypocalcaemia group (p = 0.004 and p < 0.001). The decrease of PTH levels was
more pronounced in the hypocalcaemia group, with significance on the first day
(22.29% vs 50.29%, p < 0.001). The best predictor of hypocalcaemia identified was
the decrease of parathyroid hormone levels > 19.4% determined on the 1st day
(sensitivity = 82%; specificity = 63%). DISCUSSION: In our study there was a high
incidence of hypocalcemia (60%), expressed predominantly 24 hours after surgery
and conditioned, in these patients, a longer hospital stay. However, only 3
patients (3%) had permanent hypocalcemia. We still found a match in the
oscillation of serum calcium levels and parathyroid hormone which identified the
decrease in parathyroid hormone on the first day after surgery as a reliable
predictor of hypocalcemia. CONCLUSION: Decrease of parathyroid hormone levels >
19.4% determined on 1st day is a good predictor of hypocalcemia after total /
completation thyroidectomy, allowing to identify patients at higher risk of
hypocalcemia, medicate them prophylactically and get early and safe discharges.
PMID- 26421785
TI - Hansen Neuropathy: Still a Possible Diagnosis in the Investigation of a
Peripheral Neuropathy.
AB - INTRODUCTION: Leprosy is still one of the most frequent causes of peripheral
neuropathy. Although regarded as eradicated in Portugal, is still documented in
neuropathological study of patients with clinical peripheral neuropathy without
proper diagnosis. MATERIAL AND METHODS: Review of the cases of Hansen disease
neuropathy diagnosed in Neuropathology Unit of Centro Hospitalar do Porto between
1978 and 2013, atending to gender, age, clinical manifestations and
neuropathological findings. RESULTS: Twenty one patients were identified with
neuropathological diagnosis of Hansenas disease neuropathy, predominantly male.
The mean age at diagnosis was 52 years, and sensory symptoms predominate as
neurological manifestation of disease. Interval between symptoms and diagnosis
was 1-38 years. In most nerve samples tuberculoid type of disease was identified.
Bacilli were detected in skin and nerve in 44% of cases. DISCUSSION: Mononeuritis
is the most common presentation of leprosy but other clinical manifestations are
possible, including skin lesions. Infection with M. leprae injures myelinated and
unmyelinated fibres, with replacement of nerve tissue by collagen fibrosis. The
diagnosis of leprosy is only achieved by neuropathological study of skin lesions
and / or peripheral nerve, supported by the identification of the bacillus.
CONCLUSION: Hansen disease remains a public health problem in tropical areas and,
although rare, still described in Western countries reason why should still be
considered as a diagnostic possibility in the investigation of peripheral
neuropathy.
PMID- 26421787
TI - Invasive Meningococcal Disease: Application of Base Excess and Platelets Score in
a Portuguese Paediatric Intensive Care Unit.
AB - INTRODUCTION: Meningococcal infection has a high mortality and morbidity.
Recently a new prognostic scoring system was developed for paediatric invasive
meningococcal disease, based on platelet count and base excess a base excess and
platelets score. The main objective of this study was to evaluate the accuracy of
base excess and platelets score to predict mortality in children admitted to
intensive care due to invasive meningococcal disease. MATERIAL AND METHODS:
Observational study, with retrospective data collection, during a 13.5 years
period (01/2000 to 06/2013). Mortality by invasive meningococcal disease and
related factors (organ dysfunction and multi-organ failure) were analysed. The
base excess and platelets score was calculated retrospectively, to evaluate its
accuracy in predicting mortality and compared with Paediatric Risk of Mortality
and Paediatric Index of Mortality2. RESULTS: Were admitted 76 children with
invasive meningococcal disease. The most frequent type of dysfunction was
cardiovascular (92%), followed by hematologic (55%). Of the total, 47 patients
(62%) had criteria for multi-organ failure. The global mortality was 16%.
Neurologic and renal dysfunction showed the strongest association with mortality,
adjusted odds ratio 315 (26 - 3 804) and 155 (20 - 1 299). After application of
receiver operating characteristic curves, Base Excess and Platelets score had an
area under curve of 0.81, Paediatric Index of Mortality2 of 0.91 and Paediatric
Risk of Mortality of 0.96. DISCUSSION: The Base Excess and Platelets score showed
good accuracy, although not as high as Paediatric Risk of Mortality or Paediatric
Index of Mortality2. CONCLUSIONS: The Base Excess and Platelets score may be
useful tool in invasive meningococcal disease because is highly sensitive and
specific and is objectively measurable and readily available at presentation.
PMID- 26421786
TI - Cystatin C: A Promising Marker of Renal Function in Patients with Systemic Lupus
Erythematosus?
AB - PURPOSE: Cystatin C has a higher correlation with glomerular filtration rate and
a more significant clinical prognosis than creatinine. We sought to determine
whether it is a marker of renal function different from creatinine (cystatin C
potentially superior to creatinine), in patients with systemic lupus
erythematosus. MATERIAL AND METHODS: 37 patients with systemic lupus
erythematosus were evaluated. Serum cystatin C was determined by nephelometry and
creatinine by modified Jaffe method. We compared five formulas: Chronic Kidney
Disease a Epidemiology Collaboration cystiatin; Chronic Kidney Disease a
Epidemiology Collaboration creatinine-cystatin; Cockcroft-Gault; Modification of
Diet in Renal Disease and Chronic Kidney Disease a Epidemiology Collaboration
creatinine, using the latter as a reference. We analyzed the influence of
clinical and laboratory factors in cystatin C variation, using multivariate
linear regression. RESULTS: Cystatin C was singly elevated in ten participants,
versus none isolated creatinine elevation, and this difference was significant (p
= 0.002). There was a difference between the estimated glomerular filtration rate
by Chronic Kidney Disease a Epidemiology Collaboration cystatin and by Chronic
Kidney Disease a Epidemiology Collaboration creatinine (-6.0541 mL/min/1.73 m2, p
= 0.07), more pronounced for lower glomerular filtration rate. Consequently,
Chronic Kidney Disease a Epidemiology Collaboration cystatin reclassified 4
patients as having chronic kidney disease de novo and 1 patient as not having
chronic kidney disease (p = 0.375). Cystatin C was only significantly influenced
by age (p < 0.001). DISCUSSION: Several reports showed cystatin C as a better
marker to define chronic kidney disease, allowing more accurate classification
and risk stratification, compared with creatinine. In this study, Cystatin C
revealed as a promisor marker of renal function in patient with lupus, mainly in
patients with lower glomerular filtration rates. The correlation between age and
cystatin C seems to be a confounding factor, as glomerular filtration rate
physiologically declines with ageing. CONCLUSION: Cystatin C was potentially
superior to creatinine and in this study and cystatin C seems to detect changes
in glomerular filtration rate earlier than creatinine and may be a better
screening method for chronic kidney disease in systemic lupus erythematosus.
PMID- 26421788
TI - Validation of the Portuguese Version of EHP-30 (The Endometriosis Health Profile
30).
AB - INTRODUCTION: Endometriosis Health Profile Questionnaire-30 is currently the most
used questionnaire for quality of life measurement in women with endometriosis.
The aim of this study is to evaluate the psychometric properties and to validate
the Portuguese Endometriosis Health Profile Questionnaire-30 version. MATERIAL
AND METHODS: A sequential sample of 152 patients with endometriosis, followed in
a Portugal reference center, were asked to complete a questionnaire on social and
demographic features, the Portuguese version of the Endometriosis Health Profile
Questionnaire-30 and of the Short Form Health Survey 36 Item a version 2.
Appropriate statistical analysis was performed using descriptive statistics,
factor analysis, internal consistency, item-total correlation and convergent
validity. RESULTS: Factorial analysis confirmed the validity of the five
dimension structure of the Endometriosis Health Profile Questionnaire-30 core
questionnaire, which explained 83.2% of the total variance. All item-total
correlations presented acceptable results and high internal consistency, with
Cronbach's alpha ranging between 0.876 and 0.981 for the core questionnaire and
between 0.863 and 0.951 for the modular questionnaire. Significant negative
associations between similar scales of Endometriosis Health Profile Questionnaire
30 and Short Form Health Survey 36 Item a version 2 were demonstrated. Data
completeness achieved was high for all dimensions. The emotional well-being scale
in the core questionnaire and the infertility scale in the modular section had
the highest median scores, and therefore the most negative impact on the quality
of life of participating women. DISCUSSION: The test-retest reliability and
responsiveness of the questionnaire should be evaluated in future studies.
CONCLUSION: The present study demonstrates that the Portuguese version of the
Endometriosis Health Profile Questionnaire-30 is a valid, reliable and acceptable
tool for evaluating the health-related quality of life of Portuguese women with
endometriosis.
PMID- 26421790
TI - Genetic Heterogeneity in Colorectal Cancer and its Clinical Implications.
AB - Despite the recent advances in the development of complementary diagnostic exams
and modern targeted therapies, colorectal cancer remains a major cause of
morbidity and mortality worldwide. In this context, a lot of research has been
conducted in the last years to find new markers of poor prognosis. The existence
of a complex tumour architecture formed by multiple subclones genetically
heterogeneous has been increasingly considered in recent studies as an element of
particular importance. This feature seems to influence factors as relevant as the
representativeness of tumour biopsies for genetic diagnosis and the efficacy of
targeted therapies.There is growing evidence suggesting a relation between
genetic heterogeneity and the patientsa prognosis. The widespread use of next
generation sequencing techniques will allow a better understanding of the true
degree of genetic heterogeneity in colorectal tumours, its causes and impact on
the course of the disease. In this review we intend to analyse the recent
findings related to the genetic heterogeneity of colorectal cancer, as well as
its major clinical implications.
PMID- 26421789
TI - Prognostic Factors after Liver Resection for Colorectal Liver Metastasis.
AB - INTRODUCTION: Surgery is the only potentially curative treatment for patients
with colorectal liver metastases, resulting in 5-year survival rates of 36 -??
58. Although many studies have been performed to determine prognostic factors for
tumor recurrence and survival after resection of colorectal liver metastases,
there are few prognostic scoring systems stratifying patients undergoing surgery
for colorectal liver metastases into risk group models. OBJECTIVES: To identify,
evaluate and compare the existing prognostic scores for survival after surgery
for resection of colorectal liver metastases. MATERIAL AND METHODS: Electronic
search in PubMed, Cochrane and Embase from 1990 to 2013 using the terms
'??hepatic resection', '??colorectal cancer'??, 'liver metastasis',
'??hepatectomy', '??prognostic'??, and '??score'??. Only studies proposing a
prognostic model or risk stratification based on clinical and/or pathological
variables were included. RESULTS: From 1996 to June 2013, 19 scoring systems were
identified, including one nomogram. Thirty prognostic factors were identified
although none of the factors was common to all prognostic models. The 4 factors
most often included were: number of liver metastases, regional lymph node
metastization of primary tumor, preoperative CEA level and maximum size of
metastases. The median study sample size was 305 patients (81-1 568 patients) and
median follow-up was 33 months (16-54 months). All studies were retrospective and
used the Cox proportional hazards model for multi-variable analysis. CONCLUSION:
Several factors have been constantly reported as having prognostic value after
liver resection of colorectal livermetastases, although there is no consensus on
the ideal scoring system.
PMID- 26421791
TI - Cancer-Related Pain Management and the Optimal Use of Opioids.
AB - Pain relief is vital to the treatment of cancer. Despite the widespread use and
recognition of clinical recommendations for the management of cancer-related
pain, avoidable suffering is still prevalent in patients with malignant disease.
A gap exists between what is known about pain medical management and actual
practices of patients, caregivers, healthcare professionals and institutions.
Opioids are the pillar of the medical management of moderate to severe pain. The
prescription of opioid analgesics - by a registered medical practitioner for
absolute pain control - is a legitimate practice. In this article we look at
patients' fears and physicians' general hesitations towards morphine and alike.
We examine misconceptions that yield fallacies on the therapeutically use of
opioids and, therefore, sustain inadequate pain management.
PMID- 26421792
TI - [Urinary Tuberculosis: Serious Complications May Occur when Diagnosis is
Delayed].
AB - Genitourinary tuberculosis is the third most common form of extrapulmonary
tuberculosis, comprising 4 - 17% of extrapulmonary forms. The authors describe
the case of a patient with recurrent urinary tract infections, without isolation
of an infectious agent and without symptomatic resolution, despite antibiotic
treatment. Imaging exams showed left ureteral stenosis with moderate
hydronephrosis. The attempt of retrograde catheterization was impossible so we
opted for percutaneous nephrostomy to renal relief. Microbiological urine
analysis colleted by that way was positive for Mycobacterium tuberculosis
complex. The patient started therapy with classical quadruple therapy and
underwent nephrostomy for catheter placement. Despite therapeutic measures the
patient required nephrectomy due to nonfunctioning kidney. Genitourinary
tuberculosis is a diagnosis that should be considered in the presence of a
persistent sterile pyuria.
PMID- 26421794
TI - [Superwarfarine Poisoning].
AB - The superwarfarin-type anticoagulant rodenticides are used throughout the world
and distinguish themselves from warfarin for its high potency and long acting
anticoagulant activity. Easy access to these products enables the accidental or
deliberate human poisoning. A case of voluntary rodenticide poisoning (RATIBRONA)
by a woman who ingested an estimated 27.5 mg of bromadiolone total quantity for
two weeks, with minor bleeding episodes, whose reversal of the anticoagulant
effect with the correction of the abnormal values of the clotting tests took
about one month to reverse is reported here. The correction of the haemostasis
defects takes usually a long time and there are no treatment guidelines, but a
gradually vitamin K dosage reduction, as out patients, along with the monitoring
of the International Normalized Ratio levels, allows a safe evaluation of the
therapeutic response.
PMID- 26421793
TI - [Metallosis: A Rare Cause of Autoimmune Hemolytic Anemia].
AB - INTRODUCTION: Hemolytic anemia may be associated with multiple etiologies,
including toxic substances, such as metals, which is a rare cause. CASE STUDY: 55
year-old male, who underwent a total arthroplasty of the right hip (uncemented
prostheses with ceramic-ceramic articulation with an acetabular component
consisting of a dome composed of an alloy of titanium, aluminum and vanadium into
which fitted a ceramic 'insert'). Approximately 4 years after surgery the patient
complained of noise originating from the prosthesis which occurred on movement. A
surgical revision was performed and showed the presence of dark thick
intracapsular fluid, fracture of the ceramic acetabular 'insert' and signs of
wear of the acetabular metal dome. Extensive washing was carried out and the
fractured ceramic 'insert' was replaced for a polyethylene 'insert'. Two months
later he was referred to the Emergency Room due to worsening of his general
health, floating in the right hip and mucocutaneous jaundice. Laboratory tests
suggested autoimmune hemolytic anemia. Arthrocentesis was performed and a large
volume of metal fluid was drained off. The CT scan showed a large heterogeneous
pelvic cystic collection seeded with prosthesis fragments, suggestive of
metallosis. Hemolytic anemia was explained as toxicity of the particles and metal
ions caused by the wear of the prosthesis. The patient was started on a high-dose
steroid treatment. Afterwards, when he was stable, prosthesis components
replacement and drainage of pelvic debris fluid were carried out. DISCUSSION:
After the fracture of the ceramic 'insert' the ceramic head began to articulate
directly with the metallic acetabular component, causing noise and wear with
release of particles and ions. This caused a cystic pelvic abscess, which went
unnoticed on the first surgical revision. Surgical debridement lead to the cystic
collection extending into the adjacent tissues and the systemic circulation,
triggering serious systemic effects, such as autoimmune hemolytic anemia. The
potential toxicity of each of the metal elements of this prosthesis is unknown,
and there are still no available laboratory tests for its detection. CONCLUSION:
Metallosis is a rare cause of autoimmune hemolytic anemia.
PMID- 26421795
TI - Lingua Villosa Nigra Associated with the Use of Electronic Cigarette.
PMID- 26421796
TI - "Apple Jelly" Sign: Diascopy in Cutaneous Sarcoidosis.
PMID- 26421797
TI - [Clinical Guidelines 2.0: Translation of Tables 2 and 3 and Apendix 1 of
Schunemann HJ et al. CMAJ. 2014; 186:E123-42].
AB - Clinical Practice Guidelines are instruments to support decision to improve the
quality of clinical care. An expert group from McMaster University (Canada) has
developed - from high-quality literature sources - a guidance on the practical
steps for their development, dissemination, implementation and evaluation. This
is the 1st time anyone seeks to bring together in one document all information
regarding the Clinical Practice Guidelines. Due to the interest of this paper,
the Centre for Evidence Based Medicine at the University of Lisbon School of
Medicine contacted the authors of the article and the journal where it was
published (the Canadian Medical Association Journal) in order to translate the
most relevant parts of the article (including the practice tables), which was
agreed. This guide should be useful to those who, being interested in the
development, dissemination and implementation of Clinical Practice Guidelines,
want to ensure their intrinsic quality based on relevant and updated evidence.
PMID- 26421798
TI - [On Tentacoes de Santo Antao: The Way Things Mean].
PMID- 26421800
TI - Defining the role of radiofrequency ablation and stereotactic ablative
radiotherapy in patients with high-risk, early-stage non-small cell lung cancer.
PMID- 26421799
TI - Dopamine impairs functional integrity of rat hepatocytes through nuclear factor
kappa B activity modulation: An in vivo, ex vivo, and in vitro study.
AB - Dopamine (DA) is commonly used to maintain the hemodynamic stability of brain
dead donors despite its controversial effects on organ functions. This study
aimed at examining the hemodynamic effect of DA in a rat brain-dead model in
vivo, alteration of hepatocyte integrity in liver grafts after ex vivo
preservation, and changes in cultured clone-9 hepatocytes including cellular
viability, cell cycle, apoptotic regulators, and lipopolysaccharide (LPS)
stimulated nuclear factor kappa B (NF-kappaB) signaling machinery. Although in
vivo findings demonstrated enhanced portal venous blood flow and hepatic
microcirculatory perfusion after DA infusion, no apparent advantage was noted in
preserving hepatocyte integrity ex vivo. In vitro, prolonged exposure to high
dose DA reduced proliferation and induced G1 growth arrest of clone-9 hepatocytes
with concomitant decreases in B cell lymphoma 2 (BCL2)/B cell lymphoma 2
associated X protein (BAX) and heat shock protein 70/BAX protein ratios and
intracellular NF-kappaB p65. Moreover, DA pretreatment suppressed LPS-elicited
inhibitor of kappaBalpha phosphorylation and subsequent NF-kappaB nuclear
translocation, suggesting that DA may down-regulate NF-kappaB signaling, thereby
reducing expression of antiapoptotic regulators, such as BCL2. In conclusion,
despite augmentation of hepatic perfusion, DA infusion failed to preserve
hepatocyte integrity both in vivo and ex vivo. In vitro findings demonstrated
that high-dose DA may hamper the function of NF-kappaB signaling machinery and
eventually undermine functional integrity of hepatocytes in liver grafts.
PMID- 26421801
TI - Carbon dioxide insufflation during colonoscopy can significantly decrease post
interventional abdominal discomfort in deeply sedated patients: A prospective,
randomized, double-blinded, controlled trial.
AB - BACKGROUND AND AIM: CO2 has been reported to be absorbed from the bowel more
rapidly than air, resulting in a discomfort reduction after colonoscopy. Its role
in deeply sedated patients is limited. This study was designed to investigate the
efficacy and safety of CO2 insufflation during colonoscopy in patients deeply
sedated with propofol. METHODS: A total of 125 continuous patients were randomly
assigned to receive either CO2 (n = 63) or air (n = 62) insufflation during
propofol-sedated colonoscopy. Postcolonoscopy abdominal pain, distention, and
satisfaction were assessed at 1, 3, and 24 h after the procedure, and the
proportions of pain-free and distention-free patients were compared. Residual
bowel gas in the colon and small bowel was evaluated at 1 h after colonoscopy.
End-tidal CO2 and O2 saturation was measured for safety analysis. RESULTS: There
was a significant difference between the two groups regarding the postcolonoscopy
abdominal pain, distention, and subjective satisfaction at 1 h (P < 0.001) and 3
h (P < 0.01) after the procedure. Patients' pain and distention at 1 and 3 h
after the procedure were significantly lower in the CO2 group (P < 0.01).
Residual bowel gas in the colon and small bowel was significantly less in the CO2
group (P < 0.001). There was no significant difference in end-tidal CO2 levels
between two groups before, during, and after the procedure. CONCLUSIONS: Compared
with air, CO2 insufflation during colonoscopy reduced postcolonoscopy abdominal
discomfort and improved patients' satisfaction. It was safe to use CO2
insufflation in deeply sedated colonoscopy.
PMID- 26421802
TI - Novel RAB3GAP1 compound heterozygous mutations in Japanese siblings with Warburg
Micro syndrome.
AB - BACKGROUND: Warburg Micro syndrome (WARBM) is a rare autosomal recessive disease
characterized by postnatal growth retardation, microcephaly, severely delayed
motor and intellectual development, microcornea, congenital cataracts, optic
atrophy, and hypogonadism. While WARBM is a genetically heterogeneous condition,
RAB3GAP1 mutations account for ~40% of WARBM patients, and 69 different mutations
of various types (nonsense, missense, frameshift, and splice site mutations) have
been identified to date. PATIENTS: Japanese siblings (a 7 years 3 months old male
and a 2 years 1month old female) were found to have WARBM-compatible phenotypes.
Direct sequencing of RAB3GAP1 revealed novel compound heterozygous mutations in
the siblings: a paternally inherited missense mutation (c.560G>C; p.Arg187Pro) in
exon 7 and a maternally derived nonsense mutation (c.1009C>T; p.Arg337Ter) in
exon 12. CONCLUSION: The siblings had WARBM caused by novel mutations in
RAB3GAP1. Since molecular diagnosis permits adequate genetic counseling and
appropriate management for predicted complications such as adequate sex steroid
supplementation therapy for hypogonadism, in addition to standard supportive
therapies for developmental delay and visual dysfunction, we recommend molecular
studies for this rare condition.
PMID- 26421803
TI - Lack of Impact of Body Mass Index at Young Age on Otitis Media Occurrence During
Preschool Years: Wheezing Illnesses Study Leidsche Rijn Cohort Study.
AB - Using data on weight and height at 6 and 11 months of age and primary care
electronic health records data from 1960 children participating in the Wheezing
Illnesses Study Leidsche Rijn birth cohort study, we found that body mass index
at 6 and 11 months of age was not associated with otitis media occurrence during
the first 4 years of life.
PMID- 26421804
TI - High Prevalence of Dyslipidemia and Insulin Resistance in HIV-infected
Prepubertal African Children on Antiretroviral Therapy.
AB - BACKGROUND: Data describing the true extent of antiretroviral therapy (ART)
induced dyslipidemia and insulin resistance in perinatally infected children on
ART in Africa are sparse. METHODS: Fasting total cholesterol, low-density
lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, insulin and
glucose were performed on the first 100 of 190 pediatric ART clinic attendees.
Diet assessment was performed by a trained dietician. Lipoatrophy was formally
graded by consensus between 2 expert HIV pediatricians. Durations of previous ART
exposures, clinical stage, pre-ART viral load, nadir and current CD4 were
recorded. Dual-energy X-ray absorptiometry was performed on a subset of 42
patients selected semi-randomly. RESULTS: Prevalences of insulin resistance,
abnormal total cholesterol, LDL, HDL and triglyceride were 10%, 13%, 12%, 13% and
9%, respectively. Overall, 40% had at least 1 lipid abnormality or insulin
resistance. Adjusted mean LDL cholesterol increased by 0.24 mmol/L for each
additional year of cumulative lopinavir/r exposure (P = 0.03) after correcting
for age, gender, body mass index, previous stavudine exposure, age at ART
initiation, dietary fat and refined carbohydrate, whereas adjusted mean LDL
cholesterol was 0.9 mmol/L higher in children exposed to efavirenz within the
previous 6 months (P = 0.02). Adjusting for age, gender and ethnicity, dual
energy X-ray absorptiometry revealed that greater trunk fat and lower peripheral
subcutaneous fat were associated with elevated triglycerides but not with total
cholesterol, LDL, HDL or homeostatic model assessment. Similarly, the presence of
visually obvious lipoatrophy was associated with elevated triglycerides but not
with total cholesterol, LDL, HDL, homeostatic model assessment or lactate.
CONCLUSIONS: Prevalences of insulin resistance and dyslipidemia were high.
Cumulative lopinavir is an independent risk factor for dyslipidemia, with
efavirenz exposure having only transitory effect.
PMID- 26421805
TI - Burden of Influenza and Influenza-associated Pneumonia in the First Year of Life
in a Prospective Cohort Study in Managua, Nicaragua.
AB - BACKGROUND: Influenza is a major public health problem worldwide; however,
relatively little is known about influenza in tropical regions, especially for
infants. Additional information is required to inform public health policy
making, in particular vaccination guidelines. METHODS: Between September 2011 and
July 2013, we enrolled newborns into the Nicaraguan Birth Cohort Study. Infants
were provided primary medical care and actively followed for reverse
transcription polymerase chain reaction-confirmed influenza virus infection when
presenting with influenza-like illness or undifferentiated fever. This report
presents data pertaining to the first year of life. RESULTS: Of the 518 children
enrolled in the study, 441 participated throughout their first year of life, 71
were withdrawn, and 6 died. Overall, 13% of the participants experienced at least
1 laboratory-confirmed influenza virus infection. The overall incidence of
influenza was 15.5 cases per 100 person-years [95% confidence interval (CI): 12.2
19.5]. Infants aged 6-11 months experienced significantly higher rates of
laboratory-confirmed influenza than infants aged 0-5 months (incidence rate
ratio: 2.1; 95% CI: 1.3-3.4). The overall incidence of pneumonia was 52.6 cases
per 100 person-years (95% CI: 46.3-59.6). Three percent of the pneumonia cases
were influenza associated, and the incidence of influenza-associated pneumonia
and hospitalization was 1.7 (95% CI: 0.9-3.5) and 0.22 (95% CI: 0.03-1.55) cases
per 100 person-years, respectively. CONCLUSIONS: We found a significant burden of
influenza and influenza-associated severe respiratory outcomes in infants. Our
results support the need to explore the potential value of vaccinating pregnant
women and infants aged >6 months, as recommended by the World Health Organization
in 2012.
PMID- 26421806
TI - Disease Burden of Rotavirus Gastroenteritis in Children Residing in Germany: A
Retrospective, Hospital-based Surveillance.
AB - BACKGROUND: Representative, population-based epidemiologic data for
gastroenteritis caused by rotavirus (RV) are rare. RV vaccines were first
licensed in Europe in 2006 and recommended in 5 western federal states in 2008 or
thereafter. This study establishes a baseline for assessing the impact of
vaccination and delineates the RV disease burden in Germany today. METHODS:
Nationwide data obtained from hospitals for children 0 to 10 years of age and
transferred to the Federal Statistical Office were analyzed retrospectively.
Acute gastroenteritis cases because of RV were identified by the International
Classification of Diseases code (ICD-10) combined with the referring diagnosis
related group code. Coding quality was validated by random sampling the patient
records (n=1003). Crude and age-standardized rates per 100,000 person-years were
calculated. The rate ratios of seasonal effects and recommended immunization
adjusted for year, federal state and age were estimated using Poisson regression.
RESULTS: Between 2005 and 2010, 5,843,730 children were hospitalized; 520,606
cases were hospitalized because of acute gastroenteritis. RV caused 152,636 of
these cases or an age-standardized rate of 302 hospitalizations per 100,000
person-years. Rates were slightly higher in boys than girls, decreased with age,
and differed by federal state, year and season. Rate ratios decreased in those
western federal states that recommended immunization and were inversely
associated with vaccine doses sold. CONCLUSIONS: With an average of 25,440
children hospitalized yearly, RV infection has a great impact on the German
healthcare system. Our findings indicate that RV immunization will lead to a
decline in in-patient treatment and associated costs.
PMID- 26421807
TI - Effectiveness of novel, lower cost molecular human papillomavirus-based tests for
cervical cancer screening in rural china.
AB - This study examined the efficacy of the OncoE6TM Cervical Test, careHPVTM and
visual inspection with acetic acid (VIA) in identifying women at risk for
cervical cancer and their capability to detect incident cervical precancer and
cancer at 1-year follow-up. In a population of 7,543 women living in rural China,
women provided a self-collected and two clinician-collected specimens and
underwent VIA. All screen positive women for any of the tests, a ~ 10% random
sample of test-negative women that underwent colposcopy at baseline, and an
additional ~ 10% random sample of test-negative women who did not undergo
colposcopy at baseline (n = 3,290) were recruited. 2,904 women were rescreened 1
year later using the same tests, colposcopic referral criteria, and procedures.
Sensitivities of baseline tests to detect 1-year cumulative cervical
intraepithelial neoplasia Grade 3 or cancer (CIN3+) were 96.5% and 81.6% for
careHPVTM on clinician-collected and self-collected specimens, respectively, and
54.4% for OncoE6TM test. The OncoE6TM test was very specific (99.1%) and had the
greatest positive predictive value (PPV; 47.7%) for CIN3+. Baseline and 1-year
follow-up cervical specimens testing HPV DNA positive was sensitive (88.0%) but
poorly predictive (5.5-6.0%) of incident CIN2+, whereas testing repeat HPV16, 18
and 45 E6 positive identified only 24.0% of incident CIN2+ but had a predictive
value of 33.3%. This study highlights the different utility of HPV DNA and E6
tests, the former as a screening and the latter as a diagnostic test, for
detection of cervical precancer and cancer.
PMID- 26421808
TI - Understanding Heterogeneity in the Impact of National Neglected Tropical Disease
Control Programmes: Evidence from School-Based Deworming in Kenya.
AB - BACKGROUND: The implementation of soil-transmitted helminth (STH) treatment
programmes occurs in varied environmental, social and economic contexts.
Programme impact will be influenced by factors that affect the reduction in the
prevalence and intensity of infections following treatment, as well as the
subsequent rate of reinfection. To better understand the heterogeneity of
programme impact and its underlying reasons, we investigated the influence of
contextual factors on reduction in STH infection as part of the national school
based deworming (SBD) programme in Kenya. MATERIALS AND METHODS: Data on the
prevalence and intensity of infection were collected within the monitoring and
evaluation component of the SBD programme at baseline and after delivery of two
annual treatment rounds in 153 schools in western Kenya. Using a framework that
considers STH epidemiology and transmission dynamics, capacity to deliver
treatment, operational feasibility and financial capacity, data were assembled at
both school and district (county) levels. Geographic heterogeneity of programme
impact was assessed by descriptive and spatial analyses. Factors associated with
absolute reductions of Ascaris lumbricoides and hookworm infection prevalence and
intensity were identified using mixed effects linear regression modelling
adjusting for baseline infection levels. PRINCIPAL FINDINGS: The reduction in
prevalence and intensity of A. lumbricoides and hookworms varied significantly by
county and within counties by school. Multivariable analysis of factors
associated with programme impact showed that absolute A. lumbricoides reductions
varied by environmental conditions and access to improved sanitation at schools
or within the community. Larger reduction in prevalence and intensity of
hookworms were found in schools located within areas with higher community level
access to improved sanitation and within counties with higher economic and health
service delivery indicator scores. CONCLUSIONS: The study identifies factors
associated with the impact of school-based deworming and in particular highlights
how access to water, sanitation and hygiene and environmental conditions
influence the impact of deworming programmes.
PMID- 26421809
TI - Modification of Bupivacaine-Induced Myotoxicity with Dantrolene and Caffeine In
Vitro.
AB - BACKGROUND: Local anesthetics, especially bupivacaine, have myotoxic effects in
clinically used concentrations and context. Detailed mechanisms of these effects
are unknown, but an increase in intracellular calcium levels is suspected to be
the most important trigger. Dantrolene and caffeine modify cellular calcium
release from the sarcoplasmic reticulum. The aim of our study was to investigate
the effect of dantrolene and caffeine on bupivacaine-induced myotoxicity in
vitro. METHODS: A cell culture model of primary muscle cells of BALB/c AnNCrl
mice was established. Cells were incubated simultaneously with increasing
concentrations of bupivacaine, dantrolene, and caffeine. The fraction of dead
cells was calculated after staining with propidium iodide and analysis by flow
cytometry. The half-maximal inhibitory concentration of bupivacaine was
calculated for each concentration. Group differences were determined by using 1
way analysis of variances with subsequent post hoc 1-way Dunnett t test. RESULTS:
Both dantrolene and caffeine alone had no effect on muscle cell survival.
Increasing concentrations of bupivacaine caused increasing cell death. Dantrolene
dose-dependently reduced the fraction of necrotic cells, whereas caffeine dose
dependently increased the fraction of dead cells. CONCLUSIONS: Dantrolene
attenuated, and caffeine enhanced, bupivacaine-induced myotoxicity, presumably by
modifying sarcoplasmic calcium release. This indicates that intracellular calcium
release is an important factor for local anesthetic-induced cell death.
PMID- 26421810
TI - Perioperative Duloxetine to Improve Postoperative Recovery After Abdominal
Hysterectomy: A Prospective, Randomized, Double-Blinded, Placebo-Controlled
Study.
AB - BACKGROUND: Postsurgical quality of recovery is worse in female than that in male
patients. Duloxetine has been used successfully for the treatment of chronic pain
conditions, but its use for preventing acute postoperative pain has been limited
to a single previous study. More importantly, the effect of preoperative
duloxetine on global postoperative quality of recovery has yet to be evaluated.
The main objective of the current investigation was to evaluate the effect of
perioperative duloxetine on postoperative quality of recovery in women undergoing
abdominal hysterectomy. METHODS: The study was a prospective, randomized, placebo
controlled, double-blinded trial. Female patients undergoing abdominal
hysterectomy were randomized to receive duloxetine (60 mg orally 2 hours before
surgery and 24 hours after surgery) or an identical placebo pill. The primary
outcome was the quality of recovery-40 score at 24 hours. Secondary outcomes
included opioid consumption and postoperative pain scores. A P value <0.05 was
used to reject type I error. RESULTS: Seventy patients were recruited, and 63
completed the study. The median difference (95% confidence interval) in global
recovery scores (quality of recovery-40) at 24 hours after surgery between the
duloxetine and the placebo group was 9 (4-20) (P < 0.001). Total opioid
consumption was reduced at 24 hours in the duloxetine group compared with the
placebo group, median (interquartile range) of 1 (0-5) mg IV morphine compared
with 5.5 (0.5-9) mg IV morphine (P = 0.004). Nausea, vomiting, and time to
postanesthesia care unit discharge were not significantly reduced in the
duloxetine group compared with placebo. CONCLUSIONS: Duloxetine improves
postoperative quality of recovery after abdominal hysterectomy. In addition,
duloxetine reduces postoperative opioid consumption, even in the presence of a
robust multimodal analgesic strategy. Duloxetine seems to be a viable
pharmacologic strategy to improve postoperative quality of recovery in female
patients undergoing abdominal hysterectomy.
PMID- 26421811
TI - In reference to endoscope-assisted transoral removal of a thyroglossal duct cyst
using a frenotomy incision: A prospective clinical trial.
PMID- 26421812
TI - X-linked ichthyosis in a patient with a novel nonsense mutation in the STS gene.
PMID- 26421814
TI - Cancer survival in Europe, 1999-2007: Doing better, feeling worse?
PMID- 26421813
TI - Intermediate and long-term adverse effects of radioiodine therapy for
differentiated thyroid carcinoma--a systematic review.
AB - BACKGROUND: Treatment of differentiated thyroid carcinoma (DTC) often involves
administration of radioactive iodine (I-131) for remnant ablation or adjuvant
therapy. As DTC has favorable outcome and the incidence is increasing, concerns
have been raised about the possible adverse effects of I-131 therapy. We
systematically reviewed the literature to examine the risk of intermediate and
long-term adverse effects of I-131 therapy in DTC patients. METHODS: Multiple
electronic databases were searched up to November 2014 for English-language,
controlled studies that reported on the risk of salivary gland dysfunction,
lacrimal gland dysfunction, gonadal dysfunction, female reproductive outcomes or
second primary malignancies (SPM) after I-131 exposure. The certainty of the
evidence found was assessed using GRADE. RESULTS: In total, 37 articles met all
inclusion criteria, no studies reporting on adverse effects after I-131 treatment
focused solely on children. After exposure to I-131 for DTC, patients experienced
significantly more frequently salivary gland dysfunction (prevalence range: 16
54%, moderate-level evidence), lacrimal gland dysfunction (prevalence: 11%, low
level evidence), transient male gonadal dysfunction (prevalence: 35-100%, high
level evidence), transient female gonadal dysfunction (prevalence: 28%, low-level
evidence) and SPM (prevalence: 2.7-8.7%, moderate-level evidence) compared to
unexposed patients. I-131 therapy seems to have no deleterious effects on female
reproductive outcomes (very-low level evidence). The prevalence and severity of
adverse effects were correlated to increasing cumulative I-131 activity.
CONCLUSION: Treatment with I-131 for DTC may have significant adverse effects,
which seem to be dose dependent. These adverse effects of treatment must be
balanced when choosing for I-131 therapy in patients with DTC.
PMID- 26421815
TI - The EUROCARE-5 study on cancer survival in Europe 1999-2007: Database, quality
checks and statistical analysis methods.
AB - BACKGROUND: Since 25years the EUROCARE study monitors the survival of cancer
patients in Europe through centralised collection, quality check and statistical
analysis of population-based cancer registries (CRs) data. The European
population covered by the study increased remarkably in the latest round. The
study design and statistical methods were also changed to improve timeliness and
comparability of survival estimates. To interpret the EUROCARE-5 results on adult
cancer patients better here we assess the impact of these changes on data quality
and on survival comparisons. METHODS: In EUROCARE-5 the survival differences by
area were studied applying the complete cohort approach to data on nearly nine
million cancer patients diagnosed in 2000-2007 and followed up to 2008. Survival
time trends were analysed applying the period approach to data on about 10
million cancer cases diagnosed from 1995 to 2007 and followed up to 2008.
Differently from EUROCARE-4, multiple primary cancers were included and relative
survival was estimated with the Ederer II method. RESULTS: EUROCARE-5 covered a
population of 232 million resident persons, corresponding to 50% of the 29
participating countries. The population coverage increased particularly in
Eastern Europe. Cases identified from death certificate only (DCO) were on
average 2.9%, range 0-12%. Microscopically confirmed cases amounted to over 85%
in most CRs. Compared to previous methods, including multiple cancers and using
the Ederer II estimator reduced survival estimates by 0.4 and 0.3 absolute
percentage points, on average. CONCLUSIONS: The increased population size and
registration coverage of the EUROCARE-5 study ensures more robust and comparable
estimates across European countries. This enlargement did not impact on data
quality, which was generally satisfactory. Estimates may be slightly inflated in
countries with high or null DCO proportions, especially for poor prognosis
cancers. The updated methods improved the comparability of survival estimates
between recently and long-term established registries and reduced biases due to
informative censoring.
PMID- 26421816
TI - Age and case mix-standardised survival for all cancer patients in Europe 1999
2007: Results of EUROCARE-5, a population-based study.
AB - BACKGROUND: Overall survival after cancer is frequently used when assessing a
health care service's performance as a whole. It is mainly used by the public,
politicians and the media, and is often dismissed by clinicians because of the
heterogeneous mix of different cancers, risk factors and treatment modalities.
Here we give survival details for all cancers combined in Europe, correlating it
with economic variables to suggest reasons for differences. METHODS: We computed
age and cancer site case-mix standardised relative survival for all cancers
combined (ACRS) for 29 countries participating in the EUROCARE-5 project with
data on more than 7.5million cancer cases from 87 population-based cancer
registries, using complete and period approach. RESULTS: Denmark, United Kingdom
(UK) and Eastern European countries had lower survival than neighbouring
countries. Five-year ACRS has been increasing throughout Europe, and substantial
increases, between 1999-2001 and 2005-2007, have been achieved in countries where
survival was lower in the past. Five-year ACRS for men and women are positively
correlated with macro-economic variables like the Gross Domestic Product (GDP)
and Total National Expenditure on Health (TNEH) (R2 about 70%). Countries with
recent larger increases in GDP and TNEH had greater increases in cancer survival.
CONCLUSIONS: ACRS serves to compare all cancer survival in Europe taking account
of the geographical variability in case-mixes. The EUROCARE-5 data on ACRS
confirm previous EUROCARE findings. Survival appears to correlate with macro
economic determinants, particularly with investments in the health care system.
PMID- 26421817
TI - Prognoses and improvement for head and neck cancers diagnosed in Europe in early
2000s: The EUROCARE-5 population-based study.
AB - BACKGROUND: Head and neck (H&N) cancers are a heterogeneous group of
malignancies, affecting various sites, with different prognoses. The aims of this
study are to analyse survival for patients with H&N cancers in relation to tumour
location, to assess the change in survival between European countries, and to
investigate whether survival improved over time. METHODS: We analysed about
250,000 H&N cancer cases from 86 cancer registries (CRs). Relative survival (RS)
was estimated by sex, age, country and stage. We described survival time trends
over 1999-2007, using the period approach. Model based survival estimates of
relative excess risks (RERs) of death were also provided by country, after
adjusting for sex, age and sub-site. RESULTS: Five-year RS was the poorest for
hypopharynx (25%) and the highest for larynx (59%). Outcome was significantly
better in female than in male patients. In Europe, age-standardised 5-year
survival remained stable from 1999-2001 to 2005-2007 for laryngeal cancer, while
it increased for all the other H&N cancers. Five-year age-standardised RS was low
in Eastern countries, 47% for larynx and 28% for all the other H&N cancers
combined, and high in Ireland and the United Kingdom (UK), and Northern Europe
(62% and 46%). Adjustment for sub-site narrowed the difference between countries.
Fifty-four percent of patients was diagnosed at advanced stage (regional or
metastatic). Five-year RS for localised cases ranged between 42% (hypopharynx)
and 74% (larynx). CONCLUSIONS: This study shows survival progresses during the
study period. However, slightly more than half of patients were diagnosed with
regional or metastatic disease at diagnosis. Early diagnosis and timely start of
treatment are crucial to reduce the European gap to further improve H&N cancers
outcome.
PMID- 26421819
TI - On-going improvement and persistent differences in the survival for patients with
colon and rectum cancer across Europe 1999-2007 - Results from the EUROCARE-5
study.
AB - BACKGROUND: Previous population-based studies revealed major variation in
survival for patients with colorectal cancer (CRC) in Europe by age and between
different countries and regions, but also a sustained improvement in survival for
patients with CRC in recent years. This EUROCARE-5 paper aims to update available
knowledge from previous studies and to provide the latest survival estimates for
CRC patients from Europe. METHODS: The study analysed data of patients diagnosed
with CRC from population-based cancer registries diagnosed in 29 European
countries. Estimates of 1-year and 5-year relative survival (RS) were derived for
patients diagnosed in 2000-2007 by European region, country and age at diagnosis.
Additionally to these cohort estimates, time trends in 5-year RS were obtained
for the calendar periods 1999-2001 and 2005-2007, using the period analysis
methodology. RESULTS: European average 5-year RS for patients diagnosed with
colon and rectum cancer was 57% and 56%, respectively. The analyses showed
persistent differences in cancer survival across Europe with lowest survival for
CRC patients observed in Eastern Europe. The analyses further showed a strong
gradient in age-specific survival. Even though the study revealed sustained
improvement in patient survival between 1999-2001 and 2005-2007 (absolute
increase of 4 and 6 percentage points for colon and rectum, respectively), the
differences in the survival for CRC patients observed at the beginning of the
millennium persisted over time. CONCLUSION: Although survival for CRC patients in
Europe improved markedly in the study period, significant geographic variations
and a strong age gradient still persisted. Enhanced access to effective
diagnostic procedures and treatment options might be the keys to reducing the
existing disparities in the survival of CRC patients across Europe.
PMID- 26421820
TI - Survival in patients with primary liver cancer, gallbladder and extrahepatic
biliary tract cancer and pancreatic cancer in Europe 1999-2007: Results of
EUROCARE-5.
AB - BACKGROUND: The EUROCARE study collects and analyses survival data from
population-based cancer registries (CRs) in Europe in order to provide data on
between-country differences in survival and time trends in survival. METHODS:
This study analyses data on liver cancer, gallbladder and extrahepatic biliary
tract cancers ("biliary tract cancers"), and pancreatic cancer diagnosed in 2000
2007 from 88 CRs in 29 countries. Relative survival (RS) was estimated overall,
by region, sex, age and period of diagnosis using the complete approach. Time
trends in 5-year RS over 1999-2007 were also analysed using the period approach.
RESULTS: The prognosis of the studied cancers was poor. Age-standardised 5-year
RS was 12% for liver cancer, 17% for biliary tract cancers and 7% for pancreatic
cancer. There were some between-country differences in survival. In general, RS
was low in Eastern Europe and high in Central and Southern Europe. For all sites,
5-year RS was similar in men and women and decreased with advancing age. No
substantial changes in survival were reported for pancreatic cancer over the
period 1999-2007. On average, there was a crude increase in 5-year RS of 3
percentage points between the periods 1999-2001 and 2005-2007 for liver cancer
and biliary tract cancers. CONCLUSIONS: The major changes in imaging techniques
over the study period for the diagnosis of the three studied cancers did not
result in an improvement in the prognosis of these cancers. In the near future,
new innovative treatments might be the best way to improve the prognosis in these
cancers.
PMID- 26421821
TI - Survival of patients with skin melanoma in Europe increases further: Results of
the EUROCARE-5 study.
AB - BACKGROUND: In Europe skin melanoma (SM) survival has increased over time. The
aims were to evaluate recent trends and differences between countries and regions
of Europe. METHODS: Relative survival (RS) estimates and geographical comparisons
were based on 241,485 patients aged 15years and over with a diagnosis of invasive
SM in Europe (2000-2007). Survival time trends during 1999-2007 were estimated
using the period approach, for 213,101 patients. Age, gender, sub-sites and
morphology subgroups were considered. RESULTS: In European patients, estimated 5
year RS was 83% (95% confidence interval, CI 83-84%). The highest values were
found for patients resident in Northern (88%; 87-88%) and Central (88%; 87-88%)
Europe, followed by Ireland and United Kingdom (UK) (86%; 85-86%) and Southern
Europe (83%; 82-83%). The lowest survival was in Eastern Europe (74%; 74-75%).
Within regions the intercountry absolute difference in percentage points of RS
varied from 4% (North) to 34% (East). RS decreased markedly with patients' age
and was higher in women than men. Differences according to SM morphology and skin
sub-sites also emerged. Survival has slightly increased from 1999 to 2007, with a
small improvement in Northern and the most pronounced improvement in Eastern
Europe. DISCUSSION: SM survival is high and still increasing in European
patients. The gap between Northern and Southern and especially Eastern European
countries, although still present, diminished over time. Differences in stage
distribution at diagnosis may explain most of the geographical differences.
However, part of the improvement in survival may be attributed to overdiagnosis
from early diagnosis practices.
PMID- 26421818
TI - Survival for oesophageal, stomach and small intestine cancers in Europe 1999
2007: Results from EUROCARE-5.
AB - BACKGROUND: European regional variation in cancer survival was reported in the
EUROCARE-4 study for patients diagnosed in 1995-1999. Relative survival (RS)
estimates are here updated for patients diagnosed with cancer of the oesophagus,
stomach and small intestine from 2000 to 2007. Trends in RS from 1999-2001 to
2005-2007 are presented to monitor and discuss improvements in patient survival
in Europe. MATERIALS AND METHODS: EUROCARE-5 data from 29 countries (87 cancer
registries) were used to investigate 1- and 5-year RS. Using registry-specific
life-tables stratified by age, gender and calendar year, age-standardised
'complete analysis' RS estimates by country and region were calculated for
Northern, Southern, Eastern and Central Europe, and for Ireland and United
Kingdom (UK). Survival trends of patients in periods 1999-2001, 2002-2004 and
2005-2007 were investigated using the 'period' RS approach. We computed the 5
year RS conditional on surviving the first year (5-year conditional survival), as
the ratio of age-standardised 5-year RS to 1-year RS. RESULTS: Oesophageal cancer
1- and 5-year RS (40% and 12%, respectively) remained poor in Europe. Patient
survival was worst in Eastern (8%), Northern (11%) and Southern Europe (10%).
Europe-wide, there was a 3% improvement in oesophageal cancer 5-year survival by
2005-2007, with Ireland and the UK (3%), and Central Europe (4%) showing large
improvements. Europe-wide, stomach cancer 5-year RS was 25%. Ireland and UK (17%)
and Eastern Europe (19%) had the poorest 5-year patient survival. Southern Europe
had the best 5-year survival (30%), though only showing an improvement of 2% by
2005-2007. Small intestine cancer 5-year RS for Europe was 48%, with Central
Europe having the best (54%), and Ireland and UK the poorest (37%). Five-year
patient survival improvement for Europe was 8% by 2005-2007, with Central,
Southern and Eastern Europe showing the greatest increases (?9%). CONCLUSIONS:
Survival for these cancer sites, particularly oesophageal cancer, remains poor in
Europe with wide variation. Further investigation into the wide variation,
including analysis by histology and anatomical sub-site, will yield insights to
better monitor and explain the improvements in survival observed over time.
PMID- 26421822
TI - Survival of women with cancers of breast and genital organs in Europe 1999-2007:
Results of the EUROCARE-5 study.
AB - BACKGROUND: Survival differences across Europe for patients with cancers of
breast, uterus, cervix, ovary, vagina and vulva have been documented by previous
EUROCARE studies. In the present EUROCARE-5 study we update survival estimates
and investigate changes in country-specific and over time survival, discussing
their relationship with incidence and mortality dynamics for cancers for which
organised screening programs are ongoing. METHODS: We analysed cases archived in
over 80 population-based cancer registries in 29 countries grouped into five
European regions. We used the cohort approach to estimate 5-year relative
survival (RS) for adult (?15years) women diagnosed 2000-2007, by age, country and
region; and the period approach to estimate time trends (1999-2007) in RS for
breast and cervical cancers. RESULTS: In 2000-2007, 5-year RS was 57% overall,
82% for women diagnosed with breast, 76% with corpus uteri, 62% with cervical,
38% with ovarian, 40% with vaginal and 62% with vulvar cancer. Survival was low
for patients resident in Eastern Europe (34% ovary-74% breast) and Ireland and
the United Kingdom [Ireland/UK] (31-79%) and high for those resident in Northern
Europe (41-85%) except Denmark. Survival decreased with advancing age: markedly
for women with ovarian (71% 15-44years; 20% ?75years) and breast (86%; 72%)
cancers. Survival for patients with breast and cervical cancers increased from
1999-2001 to 2005-2007, remarkably for those resident in countries with initially
low survival. CONCLUSIONS: Despite increases over time, survival for women's
cancers remained poor in Eastern Europe, likely due to advanced stage at
diagnosis and/or suboptimum access to adequate care. Low survival for women
living in Ireland/UK and Denmark could indicate late detection, possibly related
also to referral delay. Poor survival for ovarian cancer across the continent and
over time suggests the need for a major research effort to improve prognosis for
this common cancer.
PMID- 26421823
TI - Survival of male genital cancers (prostate, testis and penis) in Europe 1999
2007: Results from the EUROCARE-5 study.
AB - BACKGROUND: We provide updated estimates of survival and survival trends of male
genital tumours (prostate, testicular and penis cancers), in Europe and across
European areas. METHODS: The complete approach was used to obtain relative
survival estimates for patients diagnosed in 2000-2007, and followed up through
2008 in 29 countries. Data came from 87 cancer registries (CRs) for prostate
tumours and from 86 CRs for testis and penis tumours. Relative survival time
trends in 1999-2007 were estimated by the period approach. Data came from 49 CRs
in 25 countries. RESULTS: We analysed 1,021,275 male genital cancer cases. Five
year relative survival was high and decreased with increasing age for all tumours
considered. We found limited variation in survival between European regions with
Eastern Europe countries having lower survival than the others. Survival for
penile cancer patients did not improve from 1999 to 2007. Survival for testicular
cancer patients remained stable at high levels since 1999. Survival for prostate
cancer patients increased over time. CONCLUSIONS: Treatment standardisation and
centralisation for very rare diseases such as penile cancers or advanced
testicular tumours should be supported. The high survival of testicular cancer
makes long-term monitoring of testicular cancer survivors necessary and CRs can
be an important resource. Prostate cancer patients' survival must be interpreted
considering incidence and mortality data. The follow-up of the European
Randomised Study of Screening for Prostate Cancer should continue to clarify the
impact of screening on prostate cancer mortality together with population based
studies including information on stage and treatments.
PMID- 26421824
TI - Urinary tract cancer survival in Europe 1999-2007: Results of the population
based study EUROCARE-5.
AB - BACKGROUND: This work presents relative survival estimates regarding urinary
tract tumours among adult patients (age?15years) diagnosed in Europe. It reports
on survival estimates of cases diagnosed in 2000-2007, and on survival time
trends from 1999-2001 to 2005-2007. METHODS: Data on 677,340 adult urinary tract
tumour patients, (429,154 cases of invasive and non-invasive bladder and 248,186
cases of invasive kidney cancers) diagnosed between 2000 and 2007 were provided
by 86 population-based cancer registries from 29 European countries. The complete
approach was used to estimate survival in 2000-2007; the period approach was used
to estimate survival over time. RESULTS: The age-standardised 5-year relative
survival for patients with kidney tumours diagnosed in Europe during 2000-2007
was 60%. The best prognosis was observed in Southern and Central Europe and
prognosis improved in all regions along the time period. For invasive and non
invasive patients with bladder tumours combined the age-standardised 5-year
relative survival in Europe was 68%. The best prognosis was observed in Southern
and Northern Europe. However, in Scotland and The Netherlands the relative
survival was significantly lower, although the survival estimates for these two
countries were based on invasive tumours only. CONCLUSIONS: Differences in
registration practices affect comparisons of survival values between European
countries, especially in patients with urinary bladder cancers. The between
country variation in survival is influenced by the varying use of diagnostic
investigation in urinary tract tumours. Further data on stage at diagnosis can
help to elucidate the influence of diagnostic intensity or early diagnosis on the
survival patterns.
PMID- 26421825
TI - Survival of adults with primary malignant brain tumours in Europe; Results of the
EUROCARE-5 study.
AB - BACKGROUND: Primary malignant brain tumours are rare but represent a serious
health burden due to their poor survival. This manuscript describes the survival
of malignant brain tumours in adults diagnosed 2000-2007 in Europe. METHODS: For
this study we analysed patients archived in 86 European population-based cancer
registries, followed up to 31st December 2008. Only primary malignant
neuroepithelial brain tumours (with pathological confirmation) and primary
malignant unspecified brain tumours without pathological confirmation were
included. We estimated 1-year and 5-year relative survival (RS) weighted by age
group and country. We also estimated country-specific and age-specific survival,
together with survival differences between time periods (for 1999-2001, 2002-2004
and 2005-2007). RESULTS: Glioblastoma represents 49% of all brain tumours,
followed by other/unspecified astrocytoma (18%),
oligodendroglioma/oligoastrocytoma (9%), ependymoma (1.5%) and embryonal tumours
(1%). Five-year RS was 20% for all tumours combined, but ranged from 58% for
ependymoma to only 6% for glioblastoma and sharply decreased with increasing age.
Differences between countries were relatively small, but generally RS in
Ireland/United Kingdom (UK) and Eastern Europe was below the average. An increase
in 1-year RS (up to 10-12%) was noted over time, being largest in Central and
Northern Europe in patients between 45 and 74years of age. CONCLUSIONS: Despite
an increase in 1-year RS in most European regions, the survival of primary
malignant brain tumours is still poor. Disparities between countries were
evident, being even larger at the end of the study period than at the beginning,
suggesting differences in availability of the latest treatment modalities.
PMID- 26421828
TI - Aluminum induces inflammatory and proteolytic alterations in human monocytic cell
line.
AB - The increasing exposure to aluminum has been linked with the development of
different human pathologies (e.g., breast cancer, myofasciitis, neurodegenerative
diseases), probably due to the consistent presence of aluminum salts in widely
diffused cosmetic products and vaccines. However, the mechanisms underlying
immunologic and proliferative alterations still remain unknown. In the present
study we investigated the ability of different aluminum compounds (i.e., aluminum
chloride vs Imject(r) Alum, a mixture of aluminum and magnesium hydroxide) to
trigger both inflammatory and proteolytic responses in U-937 human monocytic cell
line. We demonstrated, by multiplex immunoassay analyses, that monocytic cells
treated with both Imject Alum and aluminum chloride showed different and peculiar
expression profiles of 27 inflammatory mediators and 5 matrix metalloproteinases,
with respect to untreated control cells. In particular, we found dose-dependent
significantly increased levels of pro-inflammatory cytokines, growth factors, and
chemoattractant chemokines; whereas among metalloproteinases, only collagenolytic
protease showed a significant dose-dependent increase in Imject-treated cells
with respect to controls and Al-chloride treated cells. Noteworthy, we found only
in Imject Alum-treated cells the significant positive correlations among
collagenolytic metalloproteinase and increased expression of pro-inflammatory
chemokines, suggesting a possible involvement of aluminum in regulating the acute
inflammatory responses. In agreement to emerging evidences, for the first time we
demonstrated that the treatment of monocyte cells with aluminum-based adjuvant is
able to induce an inflammatory status and a proteolytic cascade activation. In
fact, the cell treatment with Imject Alum induced increased levels of several
cytokines and proteinases, suggesting these monocyte mediators as possible
biomarkers for aluminum-linked diseases. The identification of the biochemical
pathways involved in Al-induced cell injury pave the way for improving the
knowledge on the potential impact of aluminum in human physio-pathology.
PMID- 26421829
TI - Tremor in multiple sclerosis: The intriguing role of the cerebellum.
AB - Tremor is frequently encountered in multiple sclerosis (MS) patients. However,
its underlying pathophysiological mechanisms remain poorly understood. Our aim
was to assess the potential role of the cerebellum and brain stem structures in
the generation of MS tremor.We performed accelerometric (ACC) and
electromyographic(EMG) assessment of tremor in 32MS patients with manual
clumsiness. In addition to clinical examination, patients underwent a
neurophysiological exploration of the brainstem and cerebellar functions,which
consisted of blink and masseter inhibitory reflexes, cerebello-thalamo-cortical
inhibition (CTCi), and somatosensory evoked potentials. Tremor was clinically
visible in 18 patients and absent in 14. Patients with visible tremor had more
severe score of ataxia and clinical signs of cerebellar dysfunction, as well as a
more reduced CTCi on neurophysiological investigation. However, ACC and EMG
recordings confirmed the presence of a real rhythmic activity in only one
patient. In most MS patients, the clinically visible tremor corresponded to a
pseudorhythmic activity without coupling between ACC and EMG recordings.
Cerebellar dysfunction may contribute to the occurrence of this pseudorhythmic
activity mimicking tremor during posture and movement execution.
PMID- 26421830
TI - Effects of long-term whole-body vibration training on mobility in patients with
multiple sclerosis: A meta-analysis of randomized controlled trials.
AB - BACKGROUND: This meta-analysis evaluated feasibility and efficacy of long-term
whole-body vibration (WBV) training in improving mobility of multiple sclerosis
(MS) patients. METHODS: The primary search of this meta-analysis was conducted
from four electronic databases (PubMed, Sport, CINAHL and Cochrane) in order to
find all relevant randomized, controlled WBV intervention trials of MS patients
published between January 2000 and October 2013. The primary search was
complemented by a recent (Aug 2015) PubMed search. Data on patients'
characteristics and type of WBV intervention were extracted from the published
reports and supplementary material. Two researchers independently assessed the
methodological quality of these studies and outcomes. Standardized mean
differences based on the baseline-adjusted follow-up results were calculated as
indicators of the effect size (ES) of WBV training. RESULTS: Seven randomized
controlled trials (RCTs) involving 250 MS patients were found. Relevant group
based data for analysis were available from 109 patients in WBV groups and from
100 control patients; 41 patients withdrew from the studies. Quality assessment
revealed that the WBV training protocols were heterogeneous and the
methodological quality of the studies was generally poor. We found borderline
indication for improved 2-6 min walking endurance [ES=0.25 (95% CI=-0.06-0.0.55)]
favoring WBV training whereas no benefits were indicated for short-distance (20m
or less) walking speed or balance. CONCLUSION: This meta-analysis suggests that
WBV training has potential in improving walking endurance in MS patients with low
disability status. However, evidence for more severely disabled MS patients is
lacking, and further well-designed, long-term RCTs with adequate sample sizes are
needed.
PMID- 26421826
TI - Survival patterns in lung and pleural cancer in Europe 1999-2007: Results from
the EUROCARE-5 study.
AB - BACKGROUND: Survival of patients diagnosed with lung and pleura cancer is a
relevant health care indicator which is related to the availability and access to
early diagnosis and treatment facilities. Aim of this paper is to update lung and
pleural cancer survival patterns and time trends in Europe using the EUROCARE-5
database. METHODS: Data on adults diagnosed with lung and pleural cancer from 87
European cancer registries in 28 countries were analysed. Relative survival (RS)
in 2000-2007 by country/region, age and gender, and over time trends in 1999-2007
were estimated. RESULTS: Lung cancer survival is poor everywhere in Europe, with
a RS of 39% and 13% at 1 and 5years since diagnosis, respectively. A geographical
variability is present across European areas with a maximum regional difference
of 12 and 5 percentage points in 1-year and 5-year RS respectively. Pleural
cancer represents 4% of cases included in the present study with 7% 5-year RS
overall in Europe. Most pleural cancers (83%) are microscopically verified
mesotheliomas. Survival for both cancers decreases with advancing age at
diagnosis for both cancers. Slight increasing trends are described for lung
cancer. Survival over time is higher for squamous cell carcinoma and
adenocarcinomas than for small and large cell carcinoma; and better among women
than men. CONCLUSIONS: Despite the generalised although slight increase, survival
of lung and pleural cancer patients still remains poor in European countries.
Priority should be given to prevention, with tobacco control policies across
Europe for lung cancer and banning asbestos exposure for pleural cancer, and in
early diagnosis and better treatment. The management of mesothelioma needs a
multidisciplinary team and standardised health care strategies.
PMID- 26421827
TI - Survival variations by country and age for lymphoid and myeloid malignancies in
Europe 2000-2007: Results of EUROCARE-5 population-based study.
AB - BACKGROUND: Significant advances in the management of patients with lymphoid and
myeloid malignancies entered clinical practice in the early 2000's. The EUROCARE
5 study database provides an opportunity to assess the impact of these changes at
the population level by country in Europe. We provide survival estimates for
clinically relevant haematological malignancies (HM), using the International
Classification of Diseases for Oncology 3, by country, gender and age in Europe.
METHODS: We estimated age-standardised relative survival using the complete
cohort approach for 625,000 adult patients diagnosed in 2000-2007 and followed up
to 2008. Survival information was provided by 89 participating cancer registries
from 29 European countries. Mean survival in Europe was calculated as the
population weighted average of country-specific estimates. RESULTS: On average in
Europe, 5-year relative survival was highest for Hodgkin lymphoma (81%; 40,625
cases), poorest for acute myeloid leukaemia (17%; 57,026 cases), and intermediate
for non-Hodgkin lymphoma (59%; 329,204 cases), chronic myeloid leukaemia (53%;
17,713 cases) and plasma cell neoplasms (39%; 94,024 cases). Survival was
generally lower in Eastern Europe and highest in Central and Northern Europe.
Wider between country differences (>10%) were observed for malignancies that
benefited from therapeutic advances, such as chronic myeloid leukaemia, chronic
lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma and
multiple myeloma. Lower differences (<10%) were observed for Hodgkin lymphoma.
CONCLUSIONS: Delayed or reduced access to innovative and appropriate therapies
could plausibly have contributed to the observed geographical disparities between
European regions and countries. Population based survival by morphological sub
type is important for measuring outcomes of HM management. To better inform
quality of care research, the collection of detailed clinical information at the
population level should be prioritised.
PMID- 26421831
TI - Decreased regional cerebral blood flow in the bilateral thalami and medulla
oblongata determined by an easy Z-score (eZIS) analysis of (99m)Tc-ECD-SPECT
images in a case of MM2-thalamic-type sporadic Creutzfeldt-Jakob disease.
AB - We report a case of autopsy-verified MM2-thalamic-type sporadic Creutzfeldt-Jakob
disease (sCJD) in a 46-year-old patient with a 16-month history of abnormal
behavior, progressive dementia, insomnia, and speech disturbances without family
history. Neurological examination revealed progressive dementia, frontal signs,
insomnia, speech disturbance, gait disturbance and bilaterally exaggerated tendon
reflexes. Both brain MRI and cerebrospinal fluid examinations, including 14-3-3
protein, yielded normal results. An easy Z-score (eZIS) analysis for (99m)Tc
ethyl cysteinate dimer-single photon emission computed tomography ((99m)Tc-ECD
SPECT) revealed decreased regional cerebral blood flow in the bilateral thalami
and medulla oblongata. PRNP gene analysis revealed methionine homozygosity at
codon 129 without mutation. Neuropathological examinations revealed severe
neuronal loss, gliosis, and hypertrophic astrocytosis in the medial thalamus and
inferior olivary nucleus. A slight depletion of Purkinje cells was observed. PrP
immunostaining showed no obvious PrP deposits in the basal ganglia, thalamus,
cerebellum, or brainstem; however, mild synaptic-type PrP deposits with some
smaller plaque-like structures were only partially observed in the localized
region of the frontal lobe with the spongiform change. Western blot analyses of
protease-resistant PrP showed a type 2 pattern. In conclusion, eZIS analysis of
(99m)Tc-ECD-SPECT images is useful for detecting both thalamic and medullary
lesions. This is the first case of medullary lesions detected in a live patient
with MM2-thalamic-type sCJD using SPECT.
PMID- 26421832
TI - Detection of viable Mycobacterium avium subspecies paratuberculosis in powdered
infant formula by phage-PCR and confirmed by culture.
AB - Surveys from different parts of the world have reported that viable Mycobacterium
avium subsp. paratuberculosis (MAP) can be cultured from approximately 2% of
samples of retail pasteurised milk samples. Pasteurised milk is used for the
production of powdered infant formula (PIF) and therefore there is a concern that
MAP may also be present in these products. Several studies have previously
reported the detection of MAP in PIF using PCR-based assays. However, culture
based surveys of PIF have not detected viable MAP. Here we describe a phage
amplification assay coupled with PCR (page-PCR) that can rapidly detect viable
MAP in PIF. The results of a small survey showed that the phage-PCR assay
detected viable MAP in 13% (4/32) of PIF samples. Culture detected viable MAP in
9% (3/32) PIF samples, all of which were also phage-PCR positive. Direct IS900
PCR detected MAP DNA in 22% (7/32) of PIF samples. The presence of viable MAP in
PIF indicates that MAP either survived PIF manufacturing or that post-production
contamination occurred. Irrespective of the route of MAP contamination, the
presence of viable MAP in PIF is a potential public health concern.
PMID- 26421833
TI - A meta-analysis of dehydroepiandrosterone supplementation among women with
diminished ovarian reserve undergoing in vitro fertilization or intracytoplasmic
sperm injection.
AB - BACKGROUND: Evidence for the efficacy of dehydroepiandrosterone (DHEA) in
improving ovarian responsiveness among poor responders, especially women with
diminished ovarian reserve (DOR), remains inconsistent. OBJECTIVES: To evaluate
the effectiveness of DHEA in women with DOR undergoing in vitro fertilization
(IVF)/intracytoplasmic sperm injection (ICSI). SEARCH STRATEGY: PubMed and Embase
were searched for reports published in any language before October 31, 2014,
using keywords such as "DHEA," "poor ovarian response," "diminished ovarian
reserve," and "premature ovarian aging." SELECTION CRITERIA: Studies that
explored the effects of DHEA in women with DOR undergoing IVF/ICSI were included
if they evaluated the number of oocytes retrieved and/or the rates of clinical
pregnancy, implantation, and spontaneous abortion. DATA COLLECTION AND ANALYSIS:
Risk ratios (RRs) and standardized mean differences with 95% confidence intervals
(CIs) were calculated, combined with subgroup and sensitivity analyses. MAIN
RESULTS: Eight studies were included. The use of DHEA increased the clinical
pregnancy rate (RR 2.13; 95% CI 1.12-4.08). Similar results were obtained in
subgroup analyses including randomized controlled trials and case-control studies
(RR 2.57; 95% CI 1.43-4.63) and self-controlled studies (RR 3.95; 95% CI 1.28
12.19). However, the effects of DHEA on oocyte retrieval, implantation, and
abortion were not significant. CONCLUSIONS: Supplementation with DHEA has a
positive effect in women undergoing IVF/ICSI treatment for DOR.
PMID- 26421834
TI - Overview of 3-year experience with large-scale electronic portal imaging device
based 3-dimensional transit dosimetry.
AB - PURPOSE: To assess the usefulness of electronic portal imaging device (EPID)
based 3-dimensional (3D) transit dosimetry in a radiation therapy department by
analyzing a large set of dose verification results. METHODS AND MATERIALS: In our
institution, routine in vivo dose verification of all treatments is performed by
means of 3D transit dosimetry using amorphous silicon EPIDs. The total 3D dose
distribution is reconstructed using a back-projection algorithm and compared with
the planned dose distribution using 3D gamma evaluation. Dose reconstruction and
gamma evaluation software runs automatically in our clinic, and analysis results
are (almost) immediately available. If a deviation exceeds our alert criteria,
manual inspection is required. If necessary, additional phantom measurements are
performed to separate patient-related errors from planning or delivery errors.
Three-dimensional transit dosimetry results were analyzed per treatment site
between 2012 and 2014 and the origin of the deviations was assessed. RESULTS: In
total, 4689 of 15,076 plans (31%) exceeded the alert criteria between 2012 and
2014. These alerts were patient-related and attributable to limitations of our
back-projection and dose calculation algorithm or to external sources. Clinically
relevant deviations were detected for approximately 1 of 430 patient treatments.
Most of these errors were because of anatomical changes or deviations from the
routine clinical procedure and would not have been detected by pretreatment
verification. Although cone beam computed tomography scans yielded information
about anatomical changes, their effect on the dose delivery was assessed
quantitatively by means of 3D in vivo dosimetry. CONCLUSIONS: EPID-based transit
dosimetry is a fast and efficient dose verification technique. It provides more
useful information and is less time-consuming than pretreatment verification
measurements of intensity modulated radiation therapy and volumetric modulated
arc therapy. Large-scale implementation of 3D transit dosimetry is therefore a
powerful method to guarantee safe dose delivery during radiation therapy.
PMID- 26421835
TI - Patient-reported outcomes after electron radiation treatment for early-stage
palmar and plantar fibromatosis.
AB - PURPOSE: Palmar and plantar fibromatosis (PPF) is a progressive connective tissue
disorder of the hand/foot that often leads to debilitating functional impairment.
In Europe, orthovoltage radiation therapy (RT) has been demonstrated to prevent
local disease progression for up to 80% of patients with early-stage PPF. There
are limited data reporting outcomes for populations outside of Europe or using
electron RT. METHODS AND MATERIALS: Between 2008 and 2013, 44 early-stage PPF
cases received RT. RT fields involved clinically defined targets encompassing
involved areas (skin changes, cords, nodules) with at least 1.5-cm margins. En
face electrons (6-12 MeV) and bolus (0.5-1 cm) were selected individually.
Outcomes are reported for patients who participated in an institutional review
board-approved standardized questionnaire and chart review. RESULTS: Thirty-three
patients received 66 treatments (45 hands/15 feet and 6 reirradiations). Most
frequent dose schemes were 21 Gy (3 Gy in 7 fractions) and 30 Gy (3 Gy in 10
fractions with 6- to 8-week breaks after 15 Gy). Median time to follow-up survey
was 31 months. Disease progression at any location within or outside the RT
treatment field occurred in 20 of 33 patients (61%). Fourteen of 60 sites (23%)
developed in-field progression, but 4 sites were successfully reirradiated with
final local control in 50 of 60 sites (83%). RT improved pretreatment symptoms of
pain with strain at 30 of 37 sites (81%) and itch/burn sensations at 17 of 21
sites (81%). There were no reported grade >=2 late toxicities even with
reirradiation. Patient reported overall success with treatment was 31 of 33
patients (94%). CONCLUSION: PPF is a progressive disease. En face electron RT is
an effective therapy that stabilizes or improves symptoms in the majority of
patients. Reirradiation can be considered as a treatment option for in-field
progression. Patients report minimal toxicity and a high rate of satisfaction
with treatment.
PMID- 26421836
TI - Stereoselective Chlorination and Bromination of Enamides and Enamines via an
Electrostatic Attraction Effect Using (1,1-Diacetoxyiodo)benzene and a Halide
Source.
AB - The direct chlorination and bromination of (E)-enamines and (Z)-enamides to the
corresponding (Z)-configurated alpha-chloroenamines, alpha-bromoenamines, and
alpha-chloroenamides have been realized using NiCl2.6H2O or tetrabutyl ammonium
bromide as a halide source and (1,1-diacetoxyiodo)benzene as an oxidant. The high
stereoselective reactions which produce products with only (Z)-configurations can
be attributed to the structure of the intermediates, the conformations of which
are controlled by the electrostatic attractions between the positively charged
nitrogen atoms and the oxygen atoms of the carbonyl group. This type of
electrostatic effect has never been reported in olefin halogenations. For this
reason, the three-membered bromonium ion is only a minor intermediate in the
enamine bromination pathway. These methods open pathways to prepare alpha
chloroenamines and alpha-chloroenamides, which are not accessible via the
currently used methods.
PMID- 26421838
TI - Seasonal Differences in Relative Gene Expression of Putative Central Appetite
Regulators in Arctic Charr (Salvelinus alpinus) Do Not Reflect Its Annual Feeding
Cycle.
AB - The highly seasonal anadromous Arctic charr (Salvelinus alpinus) was used to
investigate the possible involvement of altered gene expression of brain
neuropeptides in seasonal appetite regulation. Pro-opiomelanocortin (POMCA1,
POMCA2), Cocaine and amphetamine regulated transcript (CART), Agouti related
Peptide (AgRP), Neuropeptide Y (NPY) and Melanocortin Receptor 4 (MC4-R) genes
were examined. The function of centrally expressed Leptin (Lep) in fish remains
unclear, so Lep (LepA1, LepA2) and Leptin Receptor (LepR) genes were included in
the investigation. In a ten months study gene expression was analysed in
hypothalamus, mesencephalon and telencephalon of immature charr held under
natural photoperiod (69 degrees 38'N) and ambient temperature and given excess
feed. From April to the beginning of June the charr did not feed and lost weight,
during July and August they were feeding and had a marked increase in weight and
condition factor, and from November until the end of the study the charr lost
appetite and decreased in weight and condition factor. Brain compartments were
sampled from non-feeding charr (May), feeding charr (July), and non-feeding charr
(January). Reverse transcription real-time quantitative PCR revealed temporal
patterns of gene expression that differed across brain compartments. The non
feeding charr (May, January) had a lower expression of the anorexigenic LepA1,
MC4-R and LepR in hypothalamus and a higher expression of the orexigenic NPY and
AgRP in mesencephalon, than the feeding charr (July). In the telencephalon, LepR
was more highly expressed in January and May than in July. These results do not
indicate that changes in central gene expression of the neuropeptides
investigated here directly induce seasonal changes in feeding in Arctic charr.
PMID- 26421837
TI - Hair and Scalp Disorders in a Tuscan Pediatric Dermatological Outpatient Clinic:
A Clinical and Epidemiological Evaluation.
AB - OBJECTIVES: The aim of this study was to evaluate the clinical and
epidemiological profile of hair and scalp disorders in children referred to the
Pediatric Dermatology Outpatient Clinic. MATERIALS AND METHODS: We performed a
retrospective study of children with hair loss problems or scalp diseases who
turned to the Pediatric Dermatology Service, Anna Meyer Pediatric Hospital,
Florence, Italy, from January 1, 2009, to December 31, 2009. Demographics,
personal and familial medical history, laboratory tests, clinical examination,
final diagnosis and therapeutic interventions were obtained from the manual chart
review. RESULTS: Of the 2,640 children who had access to the Pediatric
Dermatology Service, 190 (7.19%) had a hair or scalp disorder. Among the 190
children, 60 (31.57%) presented with nonscarring alopecia, 56 (29.47%) had benign
neoplasias, hamartomas or vascular malformations of the scalp, 51 (26.84%) had
scalp inflammatory diseases, 14 (7.36%) had scarring alopecia, 5 (2.63%) had
infections and 2 (1.05%) had infestation of the scalp. A case of constitutional
hypertrichosis (0.52%) and also a case (0.52%) of lamellar ichthyosis were
diagnosed. CONCLUSIONS: Our results underline that hair and scalp diseases
represent an important percentage of admittances to a dermatological pediatric
outpatient clinic. The variety and complexity of the diseases observed in this
study included diseases commonly found also in adulthood.
PMID- 26421839
TI - Incidence, Characteristics and Risk Factors of Acute Kidney Injury among Dengue
Patients: A Retrospective Analysis.
AB - BACKGROUND: Dengue induced acute kidney injury (AKI) imposes heavy burden of
illness in terms of morbidity and mortality. A retrospective study was conducted
to investigate incidence, characteristics, risk factors and clinical outcomes of
AKI among dengue patients. METHODOLOGY: A total 667 dengue patients (2008-2013)
were retrospectively evaluated and were stratified into AKI and non-AKI groups by
using AKIN criteria. Two groups were compared by using appropriate statistical
methods. RESULTS: There were 95 patients (14.2%) who had AKI, with AKIN-I, AKIN
II and AKIN-III in 76.8%, 16.8% and 6.4% patients, respectively. Significant
differences (P<0.05) in demographics and clinico-laboratory characteristics were
observed between patients with and without AKI. Presence of dengue hemorrhagic
fever [OR (95% CI): 8.0 (3.64-17.59), P<0.001],rhabdomyolysis [OR (95% CI): 7.9
(3.04-20.49)], multiple organ dysfunction OR (95% CI):17.9 (9.14-35.12),
P<0.001], diabetes mellitus [OR (95% CI): 4.7 (1.12-19.86), P = 0.034], late
hospitalization [OR (95% CI): 2.1 (1.12-19.86), P = 0.033] and use of nephrotoxic
drugs [OR(95% CI): 2.9 (1.12-19.86), P = 0.006] were associated with AKI. Longer
hospital stay (>3days) was also observed among AKI patients (OR = 1.3, P = 0.044)
[corrected].Additionally, 48.4% AKI patients had renal insufficiencies at
discharge that were signicantly associated with severe dengue, secondary
infection and diabetes mellitus. Overall mortality was 1.2% and all fatal cases
had AKI. CONCLUSIONS: The incidence of AKI is high at 14.2% among dengue
patients, and those with AKI portended significant morbidity, mortality, longer
hospital stay and poor renal outcomes. Our findings suggest that AKI in dengue is
likely to increase healthcare burden that underscores the need of clinicians'
alertness to this highly morbid and potentially fatal complication for optimal
prevention and management.
PMID- 26421840
TI - Thyroid metastasis from renal cell carcinoma-A case report after 9 years.
AB - INTRODUCTION: The thyroid gland is a rare site of clinically detectable tumor
metastasis. As thyroid tumors are usually assumed to be primary in origin, its
recognition as a secondary is difficult. PRESENTATION OF CASE: We report a case
of an 80-year old female who was referred to the Department of Surgery for a
symptomatic thyroid nodule. Her medical history included a radical nephrectomy
for renal cell carcinoma (RCC) nine years ago. During follow-up a pancreatic
nodule was noted suggestive of a neuroendocrine tumor and the von Hippel-Lindau
syndrome had to be ruled out. The fine-needle aspiration biopsy (FNAB) guided by
ultrasound (US) of the thyroid nodule was inconclusive and a hemithyroidectomy
and isthmectomy were performed. Histological examination revealed metastasis of a
clear cell carcinoma. DISCUSSION: RCC disseminates in an unpredictable manner and
can show late recurrences. Although secondary involvement of the thyroid gland by
RCC is rare, it is still one of the more common neoplasms to metastasize to this
site. There are no specific clinical features and few characteristic findings of
metastatic thyroid carcinoma on imaging studies. FNAB is a useful procedure to
diagnose metastatic thyroid cancer, but one should remain suspicious when the
result for malignant cells is negative or indeterminate. After thyroidectomy the
diagnosis of RCC is confirmed immunohistochemically. There is a clear survival
benefit if a surgical approach to the thyroid metastasis is chosen. CONCLUSION:
Thyroid metastasis should be considered in patients with a thyroid nodule and
positive history for RCC.
PMID- 26421841
TI - The Association between Maternal Reproductive Age and Progression of Refractive
Error in Urban Students in Beijing.
AB - PURPOSE: To investigate the association between maternal reproductive age and
their children' refractive error progression in Chinese urban students. METHODS:
The Beijing Myopia Progression Study was a three-year cohort investigation.
Cycloplegic refraction of these students at both baseline and follow-up vision
examinations, as well as non-cycloplegic refraction of their parents at baseline,
were performed. Student's refractive change was defined as the cycloplegic
spherical equivalent (SE) of the right eye at the final follow-up minus the
cycloplegic SE of the right eye at baseline. RESULTS: At the final follow-up, 241
students (62.4%) were reexamined. 226 students (58.5%) with completed refractive
data, as well as completed parental reproductive age data, were enrolled. The
average paternal and maternal age increased from 29.4 years and 27.5 years in
1993-1994 to 32.6 years and 29.2 years in 2003-2004, respectively. In the
multivariate analysis, students who were younger (beta = 0.08 diopter/year/year,
P<0.001), with more myopic refraction at baseline (beta = 0.02
diopter/year/diopter, P = 0.01), and with older maternal reproductive age (beta =
-0.18 diopter/year/decade, P = 0.01), had more myopic refractive change. After
stratifying the parental reproductive age into quartile groups, children with
older maternal reproductive age (trend test: P = 0.04) had more myopic refractive
change, after adjusting for the children's age, baseline refraction, maternal
refraction, and near work time. However, no significant association between
myopic refractive change and paternal reproductive age was found. CONCLUSIONS: In
this cohort, children with older maternal reproductive age had more myopic
refractive change. This new risk factor for myopia progression may partially
explain the faster myopic progression found in the Chinese population in recent
decades.
PMID- 26421842
TI - Hydration of Caffeine at High Temperature by Neutron Scattering and Simulation
Studies.
AB - The solvation of caffeine in water is examined with neutron diffraction
experiments at 353 K. The experimental data, obtained by taking advantage of
isotopic H/D substitution in water, were analyzed by empirical potential
structure refinement (EPSR) in order to extract partial structure factors and
site-site radial distribution functions. In parallel, molecular dynamics (MD)
simulations were carried out to interpret the data and gain insight into the
intermolecular interactions in the solutions and the solvation process. The
results obtained with the two approaches evidence differences in the individual
radial distribution functions, although both confirm the presence of caffeine
stacks at this temperature. The two approaches point to different accessibility
of water to the caffeine sites due to different stacking configurations.
PMID- 26421843
TI - Using Trust to Establish a Secure Routing Model in Cognitive Radio Network.
AB - Specific to the selective forwarding attack on routing in cognitive radio
network, this paper proposes a trust-based secure routing model. Through
monitoring nodes' forwarding behaviors, trusts of nodes are constructed to
identify malicious nodes. In consideration of that routing selection-based model
must be closely collaborative with spectrum allocation, a route request
piggybacking available spectrum opportunities is sent to non-malicious nodes. In
the routing decision phase, nodes' trusts are used to construct available path
trusts and delay measurement is combined for making routing decisions. At the
same time, according to the trust classification, different responses are made
specific to their service requests. By adopting stricter punishment on malicious
behaviors from non-trusted nodes, the cooperation of nodes in routing can be
stimulated. Simulation results and analysis indicate that this model has good
performance in network throughput and end-to-end delay under the selective
forwarding attack.
PMID- 26421844
TI - WormGender - Open-Source Software for Automatic Caenorhabditis elegans Sex Ratio
Measurement.
AB - Fast and quantitative analysis of animal phenotypes is one of the major
challenges of current biology. Here we report the WormGender open-source
software, which is designed for accurate quantification of sex ratio in
Caenorhabditis elegans. The software functions include, i) automatic recognition
and counting of adult hermaphrodites and males, ii) a manual inspection feature
that enables manual correction of errors, and iii) flexibility to use new
training images to optimize the software for different imaging conditions. We
evaluated the performance of our software by comparing manual and automated
assessment of sex ratio. Our data showed that the WormGender software provided
overall accurate sex ratio measurements. We further demonstrated the usage of
WormGender by quantifying the high incidence of male (him) phenotype in 27 mutant
strains. Mutants of nine genes (brc-1, C30G12.6, cep-1, coh-3, him-3, him-5, him
8, skr-1, unc-86) showed significant him phenotype. The WormGender is written in
Java and can be installed and run on both Windows and Mac platforms. The source
code is freely available together with a user manual and sample data at
http://www.QuantWorm.org/. The source code and sample data are also available at
http://dx.doi.org/10.6084/m9.figshare.1541248.
PMID- 26421845
TI - Electrostatic Charge on Flying Hummingbirds and Its Potential Role in
Pollination.
AB - Electrostatic phenomena are known to enhance both wind- and insect-mediated
pollination, but have not yet been described for nectar-feeding vertebrates. Here
we demonstrate that wild Anna's Hummingbirds (Calypte anna) can carry positive
charges up to 800 pC while in flight (mean +/- s.d.: 66 +/- 129 pC).
Triboelectric charging obtained by rubbing an isolated hummingbird wing against
various plant structures generated charges up to 700 pC. A metal hummingbird
model charged to 400 pC induced bending of floral stamens in four plants
(Nicotiana, Hemerocallis, Penstemon, and Aloe spp.), and also attracted falling
Lycopodium spores at distances of < 2 mm. Electrostatic forces may therefore
influence pollen transfer onto nectar-feeding birds.
PMID- 26421846
TI - The Prediction and Validation of Small CDSs Expand the Gene Repertoire of the
Smallest Known Eukaryotic Genomes.
AB - The proper prediction of the gene catalogue of an organism is essential to obtain
a representative snapshot of its overall lifestyle, especially when it is not
amenable to culturing. Microsporidia are obligate intracellular, sometimes hard
to culture, eukaryotic parasites known to infect members of every animal phylum.
To date, sequencing and annotation of microsporidian genomes have revealed a poor
gene complement with highly reduced gene sizes. In the present paper, we
investigated whether such gene sizes may have induced biases for the
methodologies used for genome annotation, with an emphasis on small coding
sequence (CDS) gene prediction. Using better delineated intergenic regions from
four Encephalitozoon genomes, we predicted de novo new small CDSs with sizes
ranging from 78 to 255 bp (median 168) and corroborated these predictions by RACE
PCR experiments in Encephalitozoon cuniculi. Most of the newly found genes are
present in other distantly related microsporidian species, suggesting their
biological relevance. The present study provides a better framework for
annotating microsporidian genomes and to train and evaluate new computational
methods dedicated at detecting ultra-small genes in various organisms.
PMID- 26421848
TI - Relationship between Cerebral Microbleeds and Liver Stiffness Determined by
Transient Elastography.
AB - BACKGROUND & AIMS: Liver fibrosis is a multifactorial disease that can affect the
development of cerebral small vessel diseases (SVDs) including cerebral
microbleeds (CMBs), leukoaraiosis, and silent infarctions. Transient elastography
can accurately assess the degree of liver fibrosis by measuring liver stiffness
(LS). In the present study, we investigated the association between SVDs and LS
values. METHODS: We recruited 300 participants (mean age 56 years, 170 men) who
underwent a comprehensive medical health check-up between January 2011 and
December 2012. Transient elastography was taken on the right lobe of the liver
through intercostal space with patients lying in the dorsal decubitus position
with the right arm in maximal abduction. Mild and significant fibrosis were
defined as LS values >5.6 and >8.0 kPa, respectively. The presence of each SVD
was determined using the FLAIR, GRE MR imaging as well as T1-, T2-weighted MR
images. We tested whether the presence and burden of each type of SVD were
different by LS values. RESULTS: Of the different types of SVDs, only the
presence (p = 0.001) and number of CMBs (p<0.001) were positively associated with
LS values. Multivariate analysis revealed that significant fibrosis (>8.0 kPa)
was an independent predictor of CMBs (odds ratio 6.079, 95% confidence interval
1.489-24.819, p = 0.012). However, leukoaraiosis and silent infarctions were not
associated with LS values (all p>0.05). CONCLUSIONS: The degree of liver
fibrosis, as assessed using transient elastography, was independently associated
with the presence and burden of CMBs in healthy, asymptomatic participants.
Understanding the link between the brain and liver may advance future research on
the pathomechanisms of CMBs.
PMID- 26421847
TI - High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype
Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry
Program.
AB - Allogeneic hematopoietic stem cell transplantation is a widely used and effective
therapy for hematopoietic malignant diseases and numerous other disorders. High
resolution human leukocyte antigen (HLA) haplotype frequency distributions not
only facilitate individual donor searches but also determine the probability with
which a particular patient can find HLA-matched donors in a registry. The
frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were
estimated among 169,995 Chinese volunteers using the sequencing-based typing
(SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA
DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and
7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16
Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995
individuals, nine distinct haplotypes displayed significant regionally specific
distributions. Among these, three were predominant in the South China region
(i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the
Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was
predominant in the South and Southwest China regions (the 18th haplotype), one
was relatively common in the Northeast and North China regions (the 94th
haplotype), and one was common in the Northeast, North and Northwest China (the
40th haplotype). In conclusion, this is the first to analyze high-resolution HLA
diversities across the entire country of China, based on a detailed and complete
data set that covered 31 provinces, autonomous regions, and municipalities.
Specifically, we also evaluated the HLA matching probabilities within and between
geographic regions and analyzed the regional differences in the HLA diversities
in China. We believe that the data presented in this study might be useful for
unrelated HLA-matched donor searches, donor registry planning, population genetic
studies, and anthropogenesis studies.
PMID- 26421849
TI - Quality of Animal Experiments in Anti-Angiogenic Cancer Drug Development--A
Systematic Review.
AB - Translation from preclinical animal research to clinical bedside has proven to be
difficult to impossible in many fields of research (e.g. acute stroke, ALS and
HIV vaccination development) with oncology showing particularly low translation
rates (5% vs. 20% for cardiovascular diseases). Several investigations on
published preclinical animal research have revealed that apart from plain species
differences, translational problems can arise from low study quality (e.g. study
design) or non-representative experimental conditions (e.g. treatment schedule).
This review assessed the published experimental circumstances and quality of anti
angiogenic cancer drug development in 232 in vivo studies. The quality of study
design was often insufficient; at least the information published about the
experiments was not satisfactory in most cases. There was no quality improvement
over time, with the exception of conflict of interest statements. This increase
presumably arose mainly because journal guidelines request such statements more
often recently. Visual inspection of data and a cluster analysis confirmed a
trend described in literature that low study quality tends to overestimate study
outcome. It was also found that experimental outcome was more favorable when a
potential drug was investigated as the main focus of a study, compared to drugs
that were used as comparison interventions. We assume that this effect arises
from the frequent neglect of blinding investigators towards treatment arms and
refer to it as hypothesis bias. In conclusion, the reporting and presumably also
the experimental performance of animal studies in drug development for oncology
suffer from similar shortcomings as other fields of research (such as stroke or
ALS). We consider it necessary to enforce experimental quality and reporting that
corresponds to the level of clinical studies. It seems that only clear journal
guidelines or guidelines from licensing authorities, where failure to fulfill
prevents publication or experimental license, can help to improve this situation.
PMID- 26421850
TI - Targeted gamma-Secretase Inhibition To Control the Notch Pathway in Renal
Diseases.
AB - Notch is a membrane inserted protein activated by the membrane-inserted gamma
secretase proteolytic complex. The Notch pathway is a potential therapeutic
target for the treatment of renal diseases but also controls the function of
other cells, requiring cell-targeting of Notch antagonists. Toward selective
targeting, we have developed the gamma-secretase inhibitor-based prodrugs 13a and
15a as substrates for gamma-glutamyltranspeptidase (gamma-GT) and/or gamma
glutamylcyclotransferase (gamma-GCT) as well as aminopeptidase A (APA), which are
overexpressed in renal diseases, and have evaluated them in experimental in vitro
and in vivo models. In nondiseased mice, the cleavage product from Ac-gamma-Glu
gamma-secretase inhibitor prodrug 13a (gamma-GT-targeting and gamma-GCT
targeting) but not from Ac-alpha-Glu-gamma-secretase inhibitor prodrug 15a (APA
targeting) accumulated in kidneys when compared to blood and liver. Potential
nephroprotective effects of the gamma-secretase inhibitor targeted prodrugs were
investigated in vivo in a mouse model of acute kidney injury, demonstrating that
the expression of Notch1 and cleaved Notch1 could be selectively down-regulated
upon treatment with the Ac-gamma-Glu-gamma-secretase-inhibitor 13a.
PMID- 26421851
TI - Structured Reporting and Communication.
PMID- 26421852
TI - Impact of Interactive e-Learning Modules on Appropriateness of Imaging Referrals:
A Multicenter, Randomized, Crossover Study.
AB - PURPOSE: Health care expenditure on diagnostic imaging investigations is
increasing, and many tests are ordered inappropriately. Validated clinical
decision rules (CDRs) for certain conditions are available to aid in assessing
the need for imaging. However, awareness and utilization of CDRs are lacking.
This study compared the efficacy and perceived impact of interactive e-learning
modules versus static versions of CDRs, for learning about appropriate imaging
referrals. METHODS: A multicenter, randomized, crossover trial was performed;
participants were volunteer medical students and recent graduates. In week 1,
group 1 received an e-learning module on appropriate imaging referrals for
pulmonary embolism; group 2 received PDF versions of relevant CDRs, and an online
quiz with feedback. In week 2, the groups crossed over, focusing on imaging
referrals for cervical spine trauma in adults. Online assessments were
administered to both groups at the end of each week, and participants completed
an online questionnaire at the end of the trial. RESULTS: Group 1 (e-learning
module) performed significantly better on the pulmonary embolism knowledge
assessment. After the crossover, participants in group 2 (e-learning module) were
significantly more likely to improve their scores in the assessment of cervical
spine trauma knowledge. Both groups gave positive evaluations of the e-learning
modules. CONCLUSIONS: Interactive e-learning was significantly more effective for
learning in this cohort, compared with static CDRs. We believe that the authentic
clinical scenarios, feedback, and integration provided by the e-learning modules
contributed to their impact. This study has implications for implementation of e
learning tools to facilitate appropriate referrals for imaging investigations in
clinical practice.
PMID- 26421853
TI - Insignificant Findings: Don't Leave Them Questioning the Significance.
PMID- 26421854
TI - Simulation for Teaching and Assessment of Nodule Perception on Chest Radiography
in Nonradiology Health Care Trainees.
AB - PURPOSE: Simulation has been used as an educational and assessment tool in
several fields, generally involving training of physical skills. To date,
simulation has found limited application in teaching and assessment of skills
related to image perception and interpretation. The goal of this pilot study was
to evaluate the feasibility of simulation as a tool for teaching and assessment
of skills related to perception of nodules on chest radiography. METHODS: This
study received an exemption from the institutional review board. Subjects
consisted of nonradiology health care trainees. Subjects underwent training and
assessment of pulmonary nodule identification skills on chest radiographs at
simulated radiology workstations. Subject performance was quantified by changes
in area under the localization receiver operating characteristic curve. At the
conclusion of the study, all subjects were given a questionnaire with five
questions comparing learning at a simulated workstation with training using
conventional materials. Statistical significance for questionnaire responses was
tested using the Wilcoxon signed rank test. RESULTS: Subjects demonstrated
statistically significant improvement in nodule identification after training at
a simulated radiology workstation (change in area under the curve, 0.1079; P =
.015). Subjects indicated that training on simulated radiology workstations was
preferable to conventional training methods for all questions; P values for all
questions were less than .01. CONCLUSIONS: Simulation may be a useful tool for
teaching and assessment of skills related to medical image perception and
interpretation. Further study is needed to determine which skills and trainee
populations may be most amenable to training and assessment using simulation.
PMID- 26421855
TI - [New Developments in Pharmacotherapy of Vertigo and Balance Disorders].
PMID- 26421856
TI - [Pharmacotherapy of Vestibular Disorders, Nystagmus and Cerebellar Disorders].
AB - There are currently different groups of drugs for the pharmacotherapy of vertigo,
nystagmus and cerebellar disorders: antiemetics; anti-inflammatories,
antimenieres, and antimigraineous medications and antidepressants,
anticonvulsants, aminopyridines as well as acetyl-DL-leucine. In acute unilateral
vestibulopathy, corticosteroids improve the recovery of peripheral vestibular
function, but currently there is not sufficient evidence for a general
recommendation. There is insufficient evidence to support the view that 16 mg t.
i. d. or 48 mg t. i. d. betahistine has an effect in Meniere's disease.
Therefore, higher dosages are recommended. In animal studies, it was shown that
betahistine increases cochlear blood flow. In vestibular paroxysmia,
oxcarbazepine was effective (one randomized controlled trial (RCT)).
Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs)
and episodic ataxia type 2 (EA2, one RCT). There has been no RCT on the efficacy
of beta-blockers or topiramate but one RCT on flunarizine in vestibular migraine.
Based on clinical experience, a treatment analogous to that for migraine without
aura can be recommended. Acetyl-DL-leucine improved cerebellar ataxia (two
observational studies); it also accelerated central compensation in an animal
model of acute unilateral lesion, but RCTs were negative. There are ongoing RCTs
on treatment of vestibular paroxysmia with carbamazepine (VESPA), acute
unilateral vestibulopathy with betahistine (BETAVEST), vestibular migraine with
metoprolol (PROVEMIG), benign paroxysmal positional vertigo with vitamin D
(VitD@BPPV), EA2 with 4-aminopyridine versus acetazolamide (EAT-2-TREAT), and
cerebellar ataxias with acetyl-DL-leucine (ALCAT).
PMID- 26421857
TI - [Evaluation of Psychiatric Disorders on the Basis of a SCID Screening].
AB - BACKGROUND: Psychiatric symptoms/syndromes such as depression, apathy, anxiety or
psychotic episodes are present in a range of neurological disorders including
Parkinson's disease. The Structured Clinical Interview for DSM-IV (SCID)
represents the gold standard for the assessment of psychiatric disorders but is
often too time-consuming for application in clinical practice. METHODS: 66
participants were examined using the screening items and the first two questions
of section A of the SCID as well as the complete version of the SCID, part I. The
accuracy of the screening and the complete SCID was evaluated, and logistic
regression was conducted to analyze factors associated with measure disagreement
between the two procedures. RESULTS: Overall, psychiatric disorders were
identified by screening in 40/66 (60.6%), as against 31/66 (47.0%) using the
complete SCID. Compared to the complete SCID, the sensitivity and specificity of
the screening items were 88% and 59%, respectively. CONCLUSION: Based on its good
sensitivity, the SCID screening may be used in clinical practice to yield an
overview of psychiatric disorders that may require treatment. Due to its moderate
specificity, however, the complete version of the SCID should be subsequently
used in cases whenever the SCID screening is positive. In any case, the SCID
screening must be regarded as inadequate for the detection of psychotic symptoms.
PMID- 26421858
TI - [Hallucinogen Persisting Perception Disorder (HPPD) and Flashback Phenomena -
Differential Diagnosis and Explanation Models].
AB - OBJECTIVE: The purpose of this article is to provide an overview of the current
research on "Hallucinogen Persisting Perception Disorder" (HPPD) and "Flashback"
phenomena. The definition and diagnostic features of "Flashback" and HPPD
remained often unclear and since the 1960 s interchangeable. METHODS: Relevant
literature was identified by means of a computerized MEDLINE search including the
years 1994-2014. Finally 75 journal articles out were included in the review.
RESULTS: Consistent with the ICD-10 (F16.70) definition "Flashback" is often used
to describe brief visual perceptual, mood, and altered states of consciousness
effects reminiscent of acute hallucinogen intoxication effects. Many users regard
flashback phenomena as benign and even pleasant. HPPD is described in DSM-5 as a
visual perceptual disorder, sometimes persisting for months or years causing
severe individual distress. The prevalence of flashback and HPPD is unknown. It
is considered to be remarkable in view of the relatively few case reports
published out of millions of hallucinogen users since the 1960 s and 1970 s.
Despite a multitude of etiological and therapeutic approaches the exact
pathophysiological mechanisms underlying HPPD remain elusive. At present HPPD
appears to be further a DSM-5-genuine but still puzzling disorder. The different
consequences including new therapeutic approaches are discussed in clinical
context.
PMID- 26421859
TI - [Willingness of Psychotherapists in Private Practice to Treat Patients With
Complex Post-Traumatic Stress and Dissociative Disorders].
AB - OBJECTIVE: Analyses of patient care with severe mental disorders. METHODS:
Psychotherapists in private praxis were interviewed about their willingness to
treat patients with a range of diagnoses in the context of post-traumatic
disorders. RESULTS: Therapists were found more willing to treat "less severe"
disorders, independent of years in practice, school of psychotherapy, a rural or
urban practice setting. Therapists criticized the quality of their training and
the health insurance review process. CONCLUSIONS: Therapists are generally
willing to treat patients with severe mental disorders, but experience limits of
competency attributed to training deficits. They further experience the
bureaucratic procedures of the health insurance review process as barriers to
accepting these patients into treatment.These results indicate that recently
developed concepts of psychotherapy for these patient groups should be more
intensively integrated into the existing training curricula. Furthermore, a
simplified health insurance review process ought to be considered.
PMID- 26421860
TI - [Relevance of Magnet Resonance Tomography in the Diagnosis and Assessment of
Course of Disease in Patients with Multiple Sclerosis].
AB - Multiple sclerosis (MS) is an inflammatory disease of the central nervous system
(CNS) with a substantial destructive axonal component that is responsible for the
permanent disability accumulating during the course of the disease. Magnetic
resonance imaging (MRI) has become the most important method in the diagnosis of
MS. The high sensitivity of the MRI permits to detect focal and diffuse
inflammatory disease involvement in vivo. In clinical routine the detection and
quantification of focal pathology contributes substantially to an early diagnosis
of MS. The detection of a substantial lesion load at the beginning of the disease
increases the probability of an early conversion to clinically definite MS and
the risk of accumulating disability in the first years of the disease. In 2001
this diagnostic and prognostic gain of information at an early stage of the
disease resulted in a conceptual shift regarding diagnostic criteria. This
concept comprises clinical and MRI criteria. The current 2010 revised criteria
follow the concept of substituting a clinical relapse by subclinical MRI activity
and allow the diagnosis of MS from one single MRI after the first relapse. This
diagnostic approach using MRI allows an early treatment within an appropriate
window of treatment opportunity.
PMID- 26421862
TI - Studies on human papillomavirus (HPV) 16 E2, E5 and E7 mRNA in HPV-positive
tonsillar and base of tongue cancer in relation to clinical outcome and
immunological parameters.
AB - OBJECTIVES: Three-year survival is 80% for human papillomavirus (HPV) positive
tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) and higher
(95-100%) in patients with tumors without HLA class I expression, or with high
CD8(+) tumor-infiltrating lymphocyte (TIL) counts. The former paradoxical, the
latter expected, but it is known that E5 and E7 can downregulate HLA class I
expression. Furthermore, upon HPV integration, E2, sometimes in combination with
E5 is lost. Here, HPV16 E2, E5 and E7 mRNA was therefore examined in relation to
HLA class I expression, TIL counts and survival. PATIENTS AND METHODS: HPV16 DNA
positive TSCC and BOTSCC biopsies, analyzed for HLA class I and CD8(+) TILs, of
133 patients, treated curatively between 2000 and 2011, were tested for HPV16 E2,
E5 and E7 mRNA expression. Totally 127 samples could be evaluated and of these
117 patients, all with HPV16/E7-mRNA-positive tumors, were included in the final
analysis. RESULTS: Most tumors (92%) expressed E7 mRNA, and of these 64% also
expressed E2 and E5 mRNA. Patients with tumors lacking E2 mRNA had worse 3-year
relapse and progression free survival (p<0.01 and p<0.05), while presence of E5
had no impact on clinical outcome. Furthermore, HLA class I expression and TILs
were not correlated to E5 or to E2 mRNA expression. CONCLUSION: Lack of E2 but
not E5 mRNA in HPV16 positive TSCC and BOTSCC was a negative prognostic marker.
Presence of HPV16 E2, E5 and E7 mRNA expression was not correlated to HLA class I
expression or CD8(+) TILs.
PMID- 26421861
TI - Effect of a Cognitive-Behavioral Prevention Program on Depression 6 Years After
Implementation Among At-Risk Adolescents: A Randomized Clinical Trial.
AB - IMPORTANCE: Adolescents whose parents have a history of depression are at risk
for developing depression and functional impairment. The long-term effects of
prevention programs on adolescent depression and functioning are not known.
OBJECTIVE: To determine whether a cognitive-behavioral prevention (CBP) program
reduced the incidence of depressive episodes, increased depression-free days, and
improved developmental competence 6 years after implementation. DESIGN, SETTING,
AND PARTICIPANTS: A 4-site randomized clinical trial compared the effect of CBP
plus usual care vs usual care, through follow-up 75 months after the intervention
(88% retention), with recruitment from August 2003 through February 2006 at a
health maintenance organization, university medical centers, and a community
mental health center. A total of 316 participants were 13 to 17 years of age at
enrollment and had at least 1 parent with current or prior depressive episodes.
Participants could not be in a current depressive episode but had to have
subsyndromal depressive symptoms or a prior depressive episode currently in
remission. Analysis was conducted between August 2014 and June 2015.
INTERVENTIONS: The CBP program consisted of 8 weekly 90-minute group sessions
followed by 6 monthly continuation sessions. Usual care consisted of any family
initiated mental health treatment. MAIN OUTCOMES AND MEASURES: The Depression
Symptoms Rating scale was used to assess the primary outcome, new onsets of
depressive episodes, and to calculate depression-free days. A modified Status
Questionnaire assessed developmental competence (eg, academic or interpersonal)
in young adulthood. RESULTS: Over the 75-month follow-up, youths assigned to CBP
had a lower incidence of depression, adjusting for current parental depression at
enrollment, site, and all interactions (hazard ratio, 0.71 [95% CI, 0.53-0.96]).
The CBP program's overall significant effect was driven by a lower incidence of
depressive episodes during the first 9 months after enrollment. The CBP program's
benefit was seen in youths whose index parent was not depressed at enrollment, on
depression incidence (hazard ratio, 0.54 [95% CI, 0.36-0.81]), depression-free
days (d = 0.34, P = .01), and developmental competence (d = 0.36, P = .04); these
effects on developmental competence were mediated via the CBP program's effect on
depression-free days. CONCLUSIONS AND RELEVANCE: The effect of CBP on new onsets
of depression was strongest early and was maintained throughout the follow-up
period; developmental competence was positively affected 6 years later. The
effectiveness of CBP may be enhanced by additional booster sessions and
concomitant treatment of parental depression. TRIAL REGISTRATION:
clinicaltrials.gov Identifier:NCT00073671.
PMID- 26421863
TI - Clinical implications of epigenetic regulation in oral cancer.
AB - Oral cancer is a high incidence cancer which is of major public health concern in
India being the most common cancer in males and fifth most common cancer in
females in India, contributing to 26% of the global oral cancer burden. The major
risk factors of oral cancer are tobacco, alcohol and high risk Human Papilloma
Virus type 16/18. However, only 3-12% of the high risk individuals with dysplasia
develop oral cancer. Thus, individual genomic variants representing the genomic
constitution and epigenetic alterations play a critical role in the development
of oral cancer. Extensive epigenetic studies on the molecular lesions including
oncogenes, tumor suppressor genes, genes associated with apoptosis, DNA damage
repair have been reported. The current review highlights epigenetic regulation
with a focus on molecular biomarkers and epidrug therapy in oral cancer.
Epigenetic regulation by hypermethylation, histone modifications and specific
microRNAs are often associated with early events and advanced stages in oral
cancer, and thus indicate epidrug therapy for intervention. The presence of
epigenetic marks in oral lesions, cancers and tumor associated mucosa emphasizes
indications as biomarkers and epidrugs with therapeutic potential for better
patient management.
PMID- 26421864
TI - Osteonecrosis of the jaw a new complication related to Ipilimumab.
PMID- 26421865
TI - Effect of Poor Access to Water and Sanitation As Risk Factors for Soil
Transmitted Helminth Infection: Selectiveness by the Infective Route.
AB - BACKGROUND: Soil-transmitted helminth (STH) infections are a public health
problem in resource-limited settings worldwide. Chronic STH infection impairs
optimum learning and productivity, contributing to the perpetuation of the
poverty-disease cycle. Regular massive drug administration (MDA) is the cardinal
recommendation for its control; along with water, sanitation and hygiene (WASH)
interventions. The impact of joint WASH interventions on STH infections has been
reported; studies on the independent effect of WASH components are needed to
contribute with the improvement of current recommendations for the control of
STH. The aim of this study is to assess the association of lacking access to
water and sanitation with STH infections, taking into account the differences in
route of infection among species and the availability of adequate water and
sanitation at home. METHODS AND FINDINGS: Cross-sectional study, conducted in
Salta province, Argentina. During a deworming program that enrolled 6957
individuals; 771 were randomly selected for stool/serum sampling for
parasitological and serological diagnosis of STH. Bivariate stratified analysis
was performed to explore significant correlations between risk factors and STH
infections grouped by mechanism of entry as skin-penetrators (hookworms and
Strongyloides stercoralis) vs. orally-ingested (Ascaris lumbricoides and
Trichuris trichiura). After controlling for potential confounders, unimproved
sanitation was significantly associated with increased odds of infection of skin
penetrators (adjusted odds ratio [aOR] = 3.9; 95% CI: 2.6-5.9). Unimproved
drinking water was significantly associated with increased odds of infection of
orally-ingested (aOR = 2.2; 95% CI: 1.3-3.7). CONCLUSIONS: Lack of safe water and
proper sanitation pose a risk of STH infections that is distinct according to the
route of entry to the human host used by each of the STH species. Interventions
aimed to improve water and sanitation access should be highlighted in the
recommendations for the control of STH.
PMID- 26421866
TI - Association between NOx exposure and deaths caused by respiratory diseases in a
medium-sized Brazilian city.
AB - Exposure to nitrogen oxides (NOx) emitted by burning fossil fuels has been
associated with respiratory diseases. We aimed to estimate the effects of NOx
exposure on mortality owing to respiratory diseases in residents of Taubate, Sao
Paulo, Brazil, of all ages and both sexes. This time-series ecological study from
August 1, 2011 to July 31, 2012 used information on deaths caused by respiratory
diseases obtained from the Health Department of Taubate. Estimated daily levels
of pollutants (NOx, particulate matter, ozone, carbon monoxide) were obtained
from the Centro de Previsao de Tempo e Estudos Climaticos Coupled Aerosol and
Tracer Transport model to the Brazilian developments on the Regional Atmospheric
Modeling System. These environmental variables were used to adjust the
multipollutant model for apparent temperature. To estimate association between
hospitalizations owing to asthma and air pollutants, generalized additive Poisson
regression models were developed, with lags as much as 5 days. There were 385
deaths with a daily mean (+/-SD) of 1.05+/-1.03 (range: 0-5). Exposure to NOx was
significantly associated with mortality owing to respiratory diseases: relative
risk (RR)=1.035 (95% confidence interval [CI]: 1.008-1.063) for lag 2, RR=1.064
(95%CI: 1.017-1.112) lag 3, RR=1.055 (95%CI: 1.025-1.085) lag 4, and RR=1.042
(95%CI: 1.010-1.076) lag 5. A 3 ug/m3 reduction in NOx concentration resulted in
a decrease of 10-18 percentage points in risk of death caused by respiratory
diseases. Even at NOx concentrations below the acceptable standard, there is
association with deaths caused by respiratory diseases.
PMID- 26421867
TI - POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat
adrenal cells.
AB - During gonad and adrenal development, the POD-1/capsulin/TCF21transcription
factor negatively regulates SF-1/NR5A1expression, with higher SF-1 levels being
associated with increased adrenal cell proliferation and tumorigenesis. In
adrenocortical tumor cells, POD-1 binds to the SF-1 E-box promoter region,
decreasing SF-1 expression. However, the modulation of SF-1 expression by POD-1
has not previously been described in normal adrenal cells. Here, we analyzed the
basal expression of Pod-1 and Sf-1 in primary cultures of glomerulosa (G) and
fasciculata/reticularis (F/R) cells isolated from male Sprague-Dawley rats, and
investigated whether POD-1 overexpression modulates the expression of endogenous
Sf-1 and its target genes in these cells. POD-1 overexpression, following the
transfection of pCMVMycPod-1, significantly decreased the endogenous levels of Sf
1 mRNA and protein in F/R cells, but not in G cells, and also decreased the
expression of the SF-1 target StAR in F/R cells. In G cells overexpressing POD-1,
no modulation of the expression of SF-1 targets, StAR and CYP11B2, was observed.
Our data showing that G and F/R cells respond differently to ectopic POD-1
expression emphasize the functional differences between the outer and inner zones
of the adrenal cortex, and support the hypothesis that SF-1 is regulated by POD
1/Tcf21 in normal adrenocortical cells lacking the alterations in cellular
physiology found in tumor cells.
PMID- 26421868
TI - Optical coherence tomography imaging of the basal ganglia: feasibility and brief
review.
AB - Optical coherence tomography (OCT) is a promising medical imaging technique that
uses light to capture real-time cross-sectional images from biological tissues in
micrometer resolution. Commercially available optical coherence tomography
systems are employed in diverse applications, including art conservation and
diagnostic medicine, notably in cardiology and ophthalmology. Application of this
technology in the brain may enable distinction between white matter and gray
matter, and obtainment of detailed images from within the encephalon. We present,
herein, the in vivo implementation of OCT imaging in the rat brain striatum. For
this, two male 60-day-old rats (Rattus norvegicus, Albinus variation, Wistar)
were stereotactically implanted with guide cannulas into the striatum to guide a
2.7-French diameter high-definition OCT imaging catheter (DragonflyTM, St. Jude
Medical, USA). Obtained images were compared with corresponding histologically
stained sections to collect imaging samples. A brief analysis of OCT technology
and its current applications is also reported, as well as intra-cerebral OCT
feasibility on brain mapping during neurosurgical procedures.
PMID- 26421869
TI - Effects of exercise and metformin on the prevention of glucose intolerance: a
comparative study.
AB - We aimed to evaluate the effects of aerobic exercise training (4 days) and
metformin exposure on acute glucose intolerance after dexamethasone treatment in
rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into
four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX),
training dexamethasone-treated (DPE), and dexamethasone and metformin treated
group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken
on fasting rats to obtain glucose profiles. The DPE group displayed a significant
decrease in glucose values compared with the SDX group. Average glucose levels in
the DPE group did not differ from those of the DMT group, so we suggest that
exercise training corrects dexamethasone-induced glucose intolerance and improves
glucose profiles in a similar manner to that observed with metformin. These data
suggest that exercise may prevent the development of glucose intolerance induced
by dexamethasone in rats to a similar magnitude to that observed after metformin
treatment.
PMID- 26421870
TI - Correlation of cadherin-17 protein expression with clinicopathological features
and prognosis of patients with sporadic gastric cancer.
AB - This study aimed to explore the correlations between cadherin-17 (CDH17) protein
expression and the clinicopathological features and prognosis of patients with
sporadic gastric cancer (GC). Nine relevant studies of 1,960 patients were
identified using electronic database searches supplemented with a manual search
in strict accordance with inclusion and exclusion criteria. Statistical analyses
were conducted using STATA 12.0 statistical software. Relative risks and 95%
confidence intervals were determined, and Z test was used to measure the
significance of the overall effect size. A total of nine eligible cohort studies
were included in this meta-analysis. The expression of CDH17 in patients with
diffuse GC was significantly higher than in those with intestinal-type GC.
Moreover, the tumor depth of invasion differed significantly between patients
with positive CDH17 (CDH17+) and negative CDH17 (CDH17-) GC. However, there were
no significant differences between CDH17+ and CDH17- GC patients with respect to
tumor node metastasis clinical stages, histological grades, or lymph node
metastasis. Despite the differences in invasive depth, there was no significant
difference in 5-year survival rates between CDH17+ and CDH17- GC patients. Our
meta-analysis provides evidence that CDH17 protein expression may be associated
with the development of GC, suggesting that CDH17 is an important biomarker that
could be useful for the early diagnosis of GC. However, CDH17 levels do not
appear to impact overall survival.
PMID- 26421872
TI - Glycan-based diagnostic devices: current progress, challenges and perspectives.
AB - Diagnosis is an essential launching point for accurate medical treatment, and
rapid and accurate diagnostic approaches have become the increasingly vital goal
inspiring developments in a variety of analytical methods. With increasing
attention in the area of glycosciences, the roles that carbohydrates play in many
diseases have been elucidated, and the use of carbohydrates as disease biomarkers
has become an emerging diagnostics strategy. This review article does not intend
to comprehensively include all carbohydrate-related diagnostics studies. We do,
however, wish to describe carbohydrate recognition and the design of sensitive
detecting devices, especially those developed recently, so that readers might
better grasp the principles behind such devices and relevant detection
strategies, particularly those favoring inexpensive, rapid, and point-of-care
(POC) approaches.
PMID- 26421871
TI - Activation of endogenous angiotensin converting enzyme 2 prevents early injuries
induced by hyperglycemia in rat retina.
AB - Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that may
result in blindness. We evaluated the effects of activation of endogenous
angiotensin converting enzyme (ACE) 2 on the early stages of DR. Rats were
administered an intravenous injection of streptozotocin to induce hyperglycemia.
The ACE2 activator 1-[[2-(dimethylamino) ethyl] amino]-4-(hydroxymethyl)-7-[[(4
methylphenyl) sulfonyl] oxy]-9H-xanthone 9 (XNT) was administered by daily
gavage. The death of retinal ganglion cells (RGC) was evaluated in histological
sections, and retinal ACE2, caspase-3, and vascular endothelial growth factor
(VEGF) expressions were analyzed by immunohistochemistry. XNT treatment increased
ACE2 expression in retinas of hyperglycemic (HG) rats (control: 13.81+/-2.71
area%; HG: 14.29+/-4.30 area%; HG+XNT: 26.87+/-1.86 area%; P<0.05). Importantly,
ACE2 activation significantly increased the RCG number in comparison with HG
animals (control: 553.5+/-14.29; HG: 530.8+/-10.3 cells; HG+XNT: 575.3+/-16.5
cells; P<0.05). This effect was accompanied by a reduction in the expression of
caspase-3 in RGC of the HG+XNT group when compared with untreated HG rats
(control: 18.74+/-1.59; HG: 38.39+/-3.39 area%; HG+XNT: 27.83+/-2.80 area%;
P<0.05). Treatment with XNT did not alter the VEGF expression in HG animals
(P>0.05). Altogether, these findings indicate that activation of ACE2 reduced the
death of retinal ganglion cells by apoptosis in HG rats.
PMID- 26421874
TI - Sc2O@C(2v)(5)-C80: Dimetallic Oxide Cluster Inside a C80 Fullerene Cage.
AB - A new oxide cluster fullerene, Sc2O@C(2v)(5)-C80, has been isolated and
characterized by mass spectrometry, UV-vis-NIR absorption spectroscopy, cyclic
voltammetry, (45)Sc NMR, DFT calculations, and single crystal X-ray diffraction.
The crystallographic analysis unambiguously elucidated that the cage symmetry was
assigned to C(2v)(5)-C80 and suggests that the Sc2O cluster is ordered inside the
cage. The crystallographic data further reveals that the Sc1-O-Sc2 angle is much
larger than that found in Sc2O@T(d)(19151)-C76 but almost comparable to that in
Sc2O@Cs(6)-C82, suggesting that the endohedral Sc2O unit is flexible and can
display large variation in the Sc-O-Sc angle, which depends on the size and shape
of the cage. Computational studies show that there is a formal transfer of four
electrons from the Sc2O unit to the C80 cage, i.e., (Sc2O)(4+)@(C80)(4-), and the
HOMO and LUMO are mainly localized on the C80 framework. Moreover, thermal and
entropic effects are seen to be relevant in the isomer selection. Comparative
studies between the recently reported Sc2C2@C(2v)(5)-C80 and Sc2O@C(2v)(5)-C80
reveal that, despite their close structural resemblance, subtle differences exist
on the crystal structures, and the clusters exert notable impact on their
spectroscopic properties as well as interactions between the clusters and
corresponding cages.
PMID- 26421873
TI - pH Responsiveness of Multilayered Films and Membranes Made of Polysaccharides.
AB - We investigated the pH-dependent properties of multilayered films made of
chitosan (CHI) and alginate (ALG) and focused on their postassembly response to
different pH environments using a quartz crystal microbalance with dissipation
monitoring (QCM-D), swelling studies, zeta potential measurements, and dynamic
mechanical analysis (DMA). In an acidic environment, the multilayers presented
lower dissipation values and, consequently, higher moduli when compared with the
values obtained for the pH used during the assembly (5.5). When the multilayers
were exposed to alkaline environments, the opposite behavior occurred. These
results were further corroborated by the ability of this multilayered system to
exhibit a reversible swelling-deswelling behavior within the pH range from 3 to
9. The changes in the physicochemical properties of the multilayer system were
gradual and different from those of individual solubilized polyelectrolytes. This
behavior is related to electrostatic interactions between the ionizable groups
combined with hydrogen bonding and hydrophobic interactions. Beyond the pH range
of 3-9, the multilayers were stabilized by genipin cross-linking. The
multilayered films also became more rigid while the pH responsiveness conferred
by the ionizable moieties of the polyelectrolytes was preserved. This work
demonstrates the versatility and feasibility of LbL methodology to generate
inherently pH stimulus-responsive nanostructured films. Surface functionalization
using pH responsiveness endows several biomedical applications with abilities
such as drug delivery, diagnostics, microfluidics, biosensing, and biomimetic
implantable membranes.
PMID- 26421875
TI - Multicomponent Coculture System of Cancer Cells and Two Types of Stromal Cells
for In Vitro Evaluation of Anticancer Drugs.
AB - In vitro evaluation of anticancer drugs using cancer cells has long been
performed for the development of novel drugs and the selection of effective drugs
for different patients. Recent studies have suggested that tumor stromal cells
affect the drug sensitivity of cancer cells; however, most conventional culture
systems for drug evaluation lack stromal cells. In this study, we fabricated a
multicomponent coculture system that takes account of cancer-stroma interactions
for drug evaluation. In this system, small-cell and nonsmall-cell lung cancer
cells embedded in collagen gel were cocultured with two types of stromal cells,
including stromal fibroblasts and proinflammatory cytokine-secreting monocytes,
thus recreating the in vivo cancer microenvironment. Cancer drug sensitivity was
significantly altered by the presence of stromal cells. Fibroblasts induced
resistance of cancer cells to anticancer drugs. Monocytes induced the
upregulation of thymidine phosphorylase in cancer cells, promoting the conversion
of an anticancer prodrug to a cytotoxic drug, and consequently enhanced the
sensitivity of cancer cells to the anticancer prodrug. These results clearly show
the importance of incorporating stromal cells into culture systems for drug
evaluation. Our system will help to improve the accuracy of in vitro drug
evaluation and provide useful information for the in vitro recreation of cancer
microenvironments.
PMID- 26421876
TI - Thermal and magnetic properties of iron oxide colloids: influence of surfactants.
AB - Iron oxide nanoparticles (NPs) have been extensively studied in the last few
decades for several biomedical applications such as magnetic resonance imaging,
magnetic drug delivery and hyperthermia. Hyperthermia is a technique used for
cancer treatment which consists in inducing a temperature of about 41-45 degrees
C in cancerous cells through magnetic NPs and an external magnetic field.
Chemical precipitation was used to produce iron oxide NPs 9 nm in size coated
with oleic acid and trisodium citrate. The influence of both stabilizers on the
heating ability and in vitro cytotoxicity of the produced iron oxide NPs was
assessed. Physicochemical characterization of the samples confirmed that the used
surfactants do not change the particles' average size and that the presence of
the surfactants has a strong effect on both the magnetic properties and the
heating ability. The heating ability of Fe3O4 NPs shows a proportional increase
with the increase of iron concentration, although when coated with trisodium
citrate or oleic acid the heating ability decreases. Cytotoxicity assays
demonstrated that both pristine and trisodium citrate Fe3O4 samples do not reduce
cell viability. However, oleic acid Fe3O4 strongly reduces cell viability, more
drastically in the SaOs-2 cell line. The produced iron oxide NPs are suitable for
cancer hyperthermia treatment and the use of a surfactant brings great advantages
concerning the dispersion of NPs, also allowing better control of the
hyperthermia temperature.
PMID- 26421879
TI - Activation of Manganese Oxidants with Bisulfite for Enhanced Oxidation of Organic
Contaminants: The Involvement of Mn(III).
AB - MnO4(-) was activated by HSO3(-), resulting in a process that oxidizes organic
contaminants at extraordinarily high rates. The permanganate/bisulfite (PM/BS)
process oxidized phenol, ciprofloxacin, and methyl blue at pHini 5.0 with rates
(kobs ~ 60-150 s(-1)) that were 5-6 orders of magnitude faster than those
measured for permanganate alone, and ~5 to 7 orders of magnitude faster than
conventional advanced oxidation processes for water treatment. Oxidation of
phenol was fastest at pH 4.0, but still effective at pH 7.0, and only slightly
slower when performed in tap water. A smaller, but still considerable (~3 orders
of magnitude) increase in oxidation rates of methyl blue was observed with MnO2
activated by HSO3(-) (MO/BS). The above results, time-resolved spectroscopy of
manganese species under various conditions, stoichiometric analysis of pH
changes, and the effect of pyrophosphate on UV absorbance spectra suggest that
the reactive intermediate(s) responsible for the extremely rapid oxidation of
organic contaminants in the PM/BS process involve manganese(III) species with
minimal stabilization by complexation. The PM/BS process may lead to a new
category of advanced oxidation technologies based on contaminant oxidation by
reactive manganese(III) species, rather than hydroxyl and sulfate radicals.
PMID- 26421880
TI - Presentation, Endoscopic Management, and Significance of Hemostatic Clip
Migration into the Lower Urinary Tract Following Radical Prostatectomy.
AB - OBJECTIVES: Hemostatic clip migration into the lower urinary tract is a potential
complication of radical prostatectomy that may cause symptoms, anxiety, and
functional concern. Our objective was to evaluate initial presentation,
endoscopic management, and outcomes of patients with hemostatic clip migration
following radical prostatectomy. PATIENTS AND METHODS: We retrospectively
identified all patients with hemostatic clip migration at our institution from
1977 to 2012. Patient records were then reviewed to identify causative factors,
presentation, and long-term functional outcomes. RESULTS: Seventeen patients were
identified with clip migration following radical prostatectomy. Eight (47%)
patients had undergone open retropubic radical prostatectomy, and 9 (53%) had
received robot-assisted radical prostatectomy. Hemostatic clip migration was
diagnosed at a median of 8 (range, 1-252) months after prostatectomy. The
majority of patients (n = 16, 94%) were symptomatic upon the diagnosis of clip
migration. Symptoms included irritative urinary symptoms (n = 14, 82%), perineal
pain (n = 3, 18%), hematuria (n = 2, 12%), and infection (n = 2, 12%). Five (29%)
had concomitant bladder neck contracture. Fifteen (88%) underwent successful
endoscopic clip removal, whereas 2 (13%) patients required a repeat operation for
recurrent clip erosion. With a median follow-up of 1.6 years, the majority (n =
13, 87%) had complete symptom resolution after clip removal, although 2 patients
had recurrent bladder neck contracture. CONCLUSIONS: Hemostatic clip migration
after prostatectomy is often symptomatic with irritative voiding complaints,
perineal pain, hematuria, infection, or bladder neck contracture. Fortunately,
clips can be removed endoscopically with expected symptom resolution in the vast
majority of patients.
PMID- 26421877
TI - Role of Species-Specific Primary Structure Differences in Abeta42 Assembly and
Neurotoxicity.
AB - A variety of species express the amyloid beta-protein (Abeta (the term "Abeta"
refers both to Abeta40 and Abeta42, whereas "Abeta40" and "Abeta42" refer to each
isoform specifically). Those species expressing Abeta with primary structure
identical to that expressed in humans have been found to develop amyloid deposits
and Alzheimer's disease-like neuropathology. In contrast, the Abeta sequence in
mice and rats contains three amino acid substitutions, Arg5Gly, His13Arg, and
Tyr10Phe, which apparently prevent the development of AD-like neuropathology.
Interestingly, the brush-tailed rat, Octodon degus, expresses Abeta containing
only one of these substitutions, His13Arg, and does develop AD-like pathology. We
investigate here the biophysical and biological properties of Abeta peptides from
humans, mice (Mus musculus), and rats (Octodon degus). We find that each peptide
displays statistical coil -> beta-sheet secondary structure transitions,
transitory formation of hydrophobic surfaces, oligomerization, formation of
annuli, protofibrils, and fibrils, and an inverse correlation between rate of
aggregation and aggregate size (faster aggregation produced smaller aggregates).
The rank order of assembly rate was mouse > rat > Abeta42. The rank order of
neurotoxicity of assemblies formed by each peptide immediately after preparation
was Abeta42 > mouse ~ rat. These data do not support long-standing hypotheses
that the primary factor controlling development of AD-like neuropathology in
rodents is Abeta sequence. Instead, the data support a hypothesis that assembly
quaternary structure and organismal responses to toxic peptide assemblies mediate
neuropathogenetic effects. The implication of this hypothesis is that a valid
understanding of disease causation within a given system (organism, tissue, etc.)
requires the coevaluation of both biophysical and cell biological properties of
that system.
PMID- 26421881
TI - An Anomalous Formation Pathway for Dislocation-Sulfur Vacancy Complexes in
Polycrystalline Monolayer MoS2.
AB - Two-dimensional (2D) molybdenum disulfide (MoS2) has attracted significant
attention recently due to its direct bandgap semiconducting characteristics.
Experimental studies on monolayer MoS2 show that S vacancy concentration varies
greatly; while recent theoretical studies show that the formation energy of S
vacancy is high and thus its concentration should be low. We perform density
functional theory calculations to study the structures and energetics of vacancy
and interstitial in both grain boundary (GB) and grain interior (GI) in monolayer
MoS2 and uncover an anomalous formation pathway for dislocation-double S vacancy
(V2S) complexes in MoS2. In this pathway, a (5|7) defect in an S-polar GB
energetically favorably converts to a (4|6) defect, which possesses a duality:
dislocation and double S vacancy. Its dislocation character allows it to glide
into GI through thermal activation at high temperatures, bringing the double
vacancy with it. Our findings here not only explain why VS is predominant in
exfoliated 2D MoS2 and V2S is predominant in chemical vapor deposition (CVD)
grown 2D MoS2 but also reproduce GB patterns in CVD-grown MoS2. The new pathway
for sulfur vacancy formation revealed here provides important insights and
guidelines for controlling the quality of monolayer MoS2.
PMID- 26421882
TI - Exploring a Little-Known Pathway: Dermal Exposure to Phthalates in Indoor Air.
PMID- 26421883
TI - Electrochemical Imprinted Polycrystalline Nickel-Nickel Oxide Half-Nanotube
Modified Boron-Doped Diamond Electrode for the Detection of L-Serine.
AB - This paper presents a novel and versatile method for the fabrication of half
nanotubes (HNTs) using a flexible template-based nanofabrication method denoted
as electrochemical imprinting. With use of this method, polycrystalline nickel
and nickel(II) oxide (Ni-NiO) HNTs were synthesized using pulsed
electrodeposition to transfer Ni, deposited by radio frequency magnetron
sputtering on a porous polytetrafluoroethylene template, onto a boron-doped
diamond (BDD) film. The Ni-NiO HNTs exhibited semicircular profiles along their
entire lengths, with outer diameters of 50-120 nm and inner diameters of 20-50
nm. The HNT walls were formed of Ni and NiO nanoparticles. A biosensor for the
detection of L-serine was fabricated using a BDD electrode modified with Ni-NiO
HNTs, and the device demonstrated satisfactory analytical performance with high
sensitivity (0.33 MUA MUM(-1)) and a low limit of detection (0.1 MUM). The
biosensor also exhibited very good reproducibility and stability, as well as a
high anti-interference ability against amino acids such as L-leucine, L
tryptophan, L-cysteine, L-phenylalanine, L-arginine, and L-lysine.
PMID- 26421884
TI - Synthesis of 6- and 7-Membered N-Heterocycles Using alpha-Phenylvinylsulfonium
Salts.
AB - A concise synthesis of stereodefined C-substituted morpholines, piperazines,
azepines, and oxazepines in moderate to excellent yields (27% to 75%) is reported
by reaction of 1,2- or 1,3-amino alcohol/1,2- or 1,3-diamine with an alpha
phenylvinylsulfonium salt. High levels of regio- and diastereoselectivity (from
2:1 to >20:1) are observed through judicious choice of base (Cs2CO3) and solvent
(CH2Cl2). Reactions are performed at ambient temperature and open to air and do
not require anhydrous solvent. The deprotection of the N-sulfonamide protecting
groups (N-Ts and N-Ns) is also demonstrated. Factors affecting regio- and
diastereocontrol are discussed.
PMID- 26421886
TI - Community Professionals' Response to Intimate Partner Violence Against Rural
Older Women.
AB - The purpose of this study was to examine rural community professionals'
awareness, perceptions, and experience with intimate partner violence (IPV) in
late life. Using standard focus group methodology, 87 community professionals
were engaged in discussions about IPV in late life and their experience in
providing support to victims. Responses were analyzed using an open coding
process. Most professionals were not aware that IPV against older women was a
problem in their communities, although were willing to offer support if asked.
Support for older victims was provided within the purview of each profession.
Referrals to other support services were made, although collaboration did not
occur unless a health-related emergency arose in which professionals were
mandated to work together. Findings provide the groundwork for further research
on the education and training of community professionals on IPV in late life and
the development of more integrated community-based service protocols to address
this hidden, but widespread concern.
PMID- 26421887
TI - Rheumatoid arthritis in elderly and young patients.
PMID- 26421888
TI - Successful management of mad honey intoxication in a pregnant woman.
PMID- 26421890
TI - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AND WIDEFIELD FUNDUS AUTOFLUORESCENCE IN
PUNCTATE INNER CHOROIDOPATHY.
AB - PURPOSE: To present the optical coherence tomography angiography and widefield
fundus autofluorescence (FAF) imaging findings of a 34-year-old woman with
punctate inner choroidopathy and Type 2 neovascularization. METHODS: In the
retrospective case report, optical coherence tomography angiography imaging was
performed with the RTVue XR Avanti (Optovue Inc, Fremont, CA) platform, which
uses split spectrum amplitude decorrelation angiography to detect flow. PATIENTS:
Single patient with the diagnosis of punctate inner choroidopathy. RESULTS:
Spectral domain optical coherence tomography of the macula showed an inactive
submacular scar but optical coherence tomography angiography demonstrated the
fine detailed structure of a Type 2 neovascular membrane. Peripheral FAF
abnormalities were detected despite the notable absence of these lesions with
clinical examination and color fundus photography. These FAF findings were
important in guiding clinical follow-up and response to therapy. The FAF lesions
resolved with normal follow-up and treatment with oral naproxen. DISCUSSION: This
is the first case report of optical coherence tomography angiography imaging of
choroidal neovascularization associated with punctate inner choroidopathy and the
first report of widefield FAF abnormalities in punctate inner choroidopathy.
Optical coherence tomography angiography may provide a more noninvasive and
sensitive imaging system for the evaluation of choroidal neovascularization than
traditional fluorescein angiography and may provide a direct gauge of response to
therapy. Widefield FAF may improve detection of inflammatory activity of retinal
disease and monitoring of disease activity.
PMID- 26421891
TI - MULTIMODAL IMAGING OF THE RETINA AND CHOROID IN SYSTEMIC AMYLOIDOSIS.
AB - PURPOSE: To present the multimodal imaging findings of four patients with
systemic amyloidosis, renal failure, and chorioretinopathy. METHODS:
Retrospective analysis of four patients presenting to four institutions with
evidence of amyloid induced chorioretinopathy. Fundus photography,
autofluorescence, and spectral domain optical coherence tomography findings were
studied and are presented. RESULTS: Four patients with biopsy-proven systemic
amyloidosis demonstrated progressive chorioretinal degeneration with color fundus
photography and autofluorescent imaging. With spectral domain optical coherence
tomography analysis, amyloidosis-induced chorioretinopathy was characterized by a
widened choriocapillaris band, choroidal infiltration, diffuse photoreceptor
dysfunction, and thinning of the outer nuclear layer. CONCLUSION: Multimodal
imaging including spectral domain optical coherence tomography analysis in eyes
of patients with systemic amyloidosis shows deposition in the choroid. The
deposition may cause a secondary toxic and or barrier effect resulting in diffuse
retinal pigment epithelium and photoreceptor dysfunction.
PMID- 26421889
TI - Determinants of outcome among patients with acute liver failure listed for liver
transplantation in the United States.
AB - Analyses of outcomes after acute liver failure (ALF) have typically included all
ALF patients regardless of whether they were listed for liver transplantation
(LT). We hypothesized that limiting analysis to listed patients might provide
novel insights into factors associated with outcome, focusing attention on
disease evolution after listing. Listed adult ALF patients enrolled in the US
Acute Liver Failure Study Group registry between 2000 and 2013 were analyzed to
determine baseline factors associated with 21-day outcomes after listing. We
classified 617 patients (36% of overall ALF group) by 3-week outcome after study
admission: 117 were spontaneous survivors (SSs; survival without LT), 108 died
without LT, and 392 underwent LT. Only 22% of N-acetyl-p-aminophenol (APAP) ALF
patients were listed; however, this group of 173 patients demonstrated greater
illness severity: higher coma grades and more patients requiring ventilator,
vasopressor, or renal replacement therapy support. Only 62/173 (36%) of APAP
patients received a graft versus 66% for drug-induced liver injury patients, 86%
for autoimmune-related ALF, and 71% for hepatitis B-related ALF. APAP patients
were more likely to die than non-APAP patients (24% versus 17%), and the median
time to death was sooner (2 versus 4.5 days). Despite greater severity of
illness, the listed APAP group still had a SS rate of 40% versus 11% for non-APAP
causes (P < 0.001). APAP outcomes evolve rapidly, mainly to SS or death. Patients
with APAP ALF listed for LT had the highest death rate of any etiology, whereas
more slowly evolving etiologies yielded higher LT rates and, consequently, fewer
deaths. Decisions to list and transplant must be made early in all ALF patients,
particularly in those with APAP ALF.
PMID- 26421892
TI - MULTIMODAL IMAGING OF GEOGRAPHIC AREAS OF RETINAL DARKENING.
AB - PURPOSE: To describe the clinical and multimodal imaging characteristics of a
patient with unilateral asymptomatic dark retinal lesions corresponding to
ellipsoid zone hyporeflectivity on optical coherence tomography (OCT). METHODS:
The authors report a case of a 35-year-old man with HIV who presents with
asymptomatic dark geographic retinal lesions corresponding to ellipsoid zone
hyporeflectivity on OCT. Multimodal imaging techniques, including fundus color
and widefield photographs, autofluorescence, spectral domain OCT (Spectralis,
Heidelberg, Germany), prototype spectral domain OCT (Carl Zeiss Meditec, Dublin,
CA) with OCT angiography, and en face images, were performed to evaluate and
characterize the morphology of these lesions. RESULTS: Clinical examination and
multimodal imaging reveal geographic darkening of the retina. Optical coherence
tomography conveys hyporeflectivity of the ellipsoid zone band, which occurs
abruptly and is present only in the areas of geographic retinal darkening.
Optical coherence tomographic angiography shows a qualitatively similar
appearance of the vasculature from the superficial retina through the avascular
retina and the choriocapillaris, on both sides of the demarcation of retinal
darkening, and also as compared to the unaffected eye. En face images from
spectral domain OCT reveal an abrupt darkening of the tissue that localizes and
is limited to the ellipsoid zone, with similar topographic appearance across the
demarcation line. CONCLUSION: Geographic areas of darkening with photoreceptor
hyporeflectivity have been described previously as "dark without pressure." In
this case, the authors demonstrate photoreceptor hyporeflectivity that localizes
to the clinically darkened areas, without topographic qualitative differences on
en face spectral domain OCT images. The authors term these dark areas as
geographic areas of retinal darkening because of ellipsoid nonreflectivity
(GARDEN) spots.
PMID- 26421893
TI - CHIKUNGUNYA-ASSOCIATED UVEITIS AND EXUDATIVE RETINAL DETACHMENT: A CASE REPORT.
AB - PURPOSE: To report the first known case of bilateral granulomatous panuveitis
secondary to chikungunya fever in the United States, acquired by a U.S. citizen
traveling from an endemic region. METHODS: Case report. RESULTS: A 47-year-old
woman presented with 10 days of bilateral decreased vision and photophobia
concurrent with a febrile illness contracted while visiting the Dominican
Republic. She presented with bilateral granulomatous panuveitis and exudative
retinal detachments. Extensive workup was negative with the exception of positive
chikungunya virus immunoglobulin G and immunoglobulin M titers. Initially, she
responded to corticosteroid treatment but developed recurrent inflammation 3
months after completing the initial treatment. Immunomodulatory therapy was
initiated at the time of recurrence, and with immunomodulatory therapy alone her
inflammation has been controlled for 6 months. CONCLUSION: The prevalence of
chikungunya fever-related uveitis is increasing with the recent epidemics
throughout the Americas. Inflammation can occur during the febrile illness or
months later and can manifest in a variety of ways. Posterior segment
inflammation is more commonly a delayed presentation. Previous reports suggest
that chikungunya fever-related uveitis responds well to corticosteroid therapy.
This is the first reported case of recurrent inflammation. Given the wide variety
of presentations, chikungunya fever-related uveitis should be included in the
differential diagnosis of all at-risk patients presenting with acute ocular
inflammation, particularly those traveling from endemic regions.
PMID- 26421894
TI - CONGENITAL MACROVESSEL ASSOCIATED WITH CYSTOID MACULAR EDEMA AND AN IPSILATERAL
INTRACRANIAL VENOUS MALFORMATION.
AB - BACKGROUND/PURPOSE: To report a case of congenital retinal macrovessel associated
with cystoid macular edema and an ipsilateral intracranial venous malformation.
METHODS: Case report. RESULTS: A 58-year-old woman with decreased vision was
found to have a congenital retinal venous macrovessel associated with cystoid
macular edema because of tributary venous occlusion. The patient underwent
neuroimaging and an ipsilateral venous malformation of the frontal lobe was
discovered. CONCLUSION: Congenital retinal macrovessel can occasionally be
complicated by vascular occlusion and macular edema. The authors report a case of
congenital retinal macrovessel associated with an intracranial venous
malformation. Clinicians should be aware of this potential association, and
further studies are warranted.
PMID- 26421895
TI - Molecular-Scale Tools for Studying Mechanotransduction.
AB - Mechanical stimuli are known to be potent regulators of the form and function of
cells and organisms. Although biological regulation has classically been
understood in terms of principles from solution biochemistry, advancements in
many fields have led to the development of a suite of techniques that are able to
reveal the interplay between mechanical loading and changes in the biochemical
properties of proteins in systems ranging from single molecules to living
organisms. Here, we review these techniques and highlight the emergence of a new
molecular-scale understanding of the mechanisms mediating the detection and
response of cells to mechanical stimuli, a process termed mechanotransduction.
Specifically, we focus on the role of subcellular adhesion structures in sensing
the stiffness of the surrounding environment because this process is pertinent to
applications in tissue engineering as well the onset of several mechanosensitive
disease states, including cancer.
PMID- 26421897
TI - Acute Epidural Hematoma Following Acute Subdural Hematoma Evacuation in a Child
With Glanzmann Thrombasthenia.
PMID- 26421898
TI - Smoking and reverse causation create an obesity paradox in cardiovascular
disease.
AB - OBJECTIVE: Many studies find that excess weight is associated with better
survival among individuals with cardiovascular disease (CVD). Investigations were
carried out to see whether this "obesity paradox" can be explained by biases.
METHODS: The association between weight status and mortality in the US population
ages 35 and above with CVD was investigated. Data were obtained from the National
Health and Nutrition Examination Survey, 1988-2010, linked to mortality records
through 2011. To minimize biases resulting from illness-induced weight loss, a
reference category consisting of individuals who have always maintained normal
weight was used. Age-standardized mortality rates and Cox models were estimated,
comparing overweight/obesity (body mass index (BMI) >=25.0 kg m(-2) ) to normal
weight (BMI 18.5-24.9 kg m(-2) ). RESULTS: The paradox was present among those
with overweight/obesity at the time of survey (hazard ratio (HR) = 0.89; 95%
confidence interval (CI) 0.78-1.01). However, when the reference category was
limited to the always-normal-weight, the paradox disappeared (HR = 1.16; 95% CI
0.95-1.41). When analysis was additionally confined to never-smokers, mortality
risks were significantly higher in the overweight/obesity group (HR = 1.51; 95%
CI 1.07-2.15; P = 0.021). CONCLUSIONS: The findings provide support for the
hypothesis that lower mortality among individuals with CVD and overweight/obesity
is a product of biases involving reverse causation and confounding by smoking.
PMID- 26421899
TI - Reply to defining the role of radiofrequency ablation and stereotactic ablative
radiotherapy in patients with high-risk, early-stage non-small cell lung cancer.
PMID- 26421896
TI - Biomaterial Strategies for Immunomodulation.
AB - Strategies to enhance, suppress, or qualitatively shape the immune response are
of importance for diverse biomedical applications, such as the development of new
vaccines, treatments for autoimmune diseases and allergies, strategies for
regenerative medicine, and immunotherapies for cancer. However, the intricate
cellular and molecular signals regulating the immune system are major hurdles to
predictably manipulating the immune response and developing safe and effective
therapies. To meet this challenge, biomaterials are being developed that control
how, where, and when immune cells are stimulated in vivo, and that can finely
control their differentiation in vitro. We review recent advances in the field of
biomaterials for immunomodulation, focusing particularly on designing
biomaterials to provide controlled immunostimulation, targeting drugs and
vaccines to lymphoid organs, and serving as scaffolds to organize immune cells
and emulate lymphoid tissues. These ongoing efforts highlight the many ways in
which biomaterials can be brought to bear to engineer the immune system.
PMID- 26421900
TI - A decrease in protein level and a missense polymorphism of KIF17 are associated
with schizophrenia.
AB - It has been shown that the dysfunction of N-methyl-d-asparate (NMDA) receptors
mediated neurotransmission plays a role in the pathophysiology of schizophrenia.
Especially, GluN2B, a subunit of NMDA receptors, associated trafficking complex
is altered in the prefrontal cortex of schizophrenia. The kinesin superfamily
motor protein 17 (KIF17) is known as a transporter of NR2B.Previous studies
showed that a structural variant of KIF17 gene is associated with a schizophrenic
phenotype. Therefore, here we investigated KIF17 levels in postmortem prefrontal
cortex in schizophrenia and the association of a missense polymorphism
(Ile341Val) in KIF17 with schizophrenia. The protein expression of KIF17 in
schizophrenic postmortem brains was significantly lower than that in controls.
Next, the association of missense polymorphisms (rs631375, rs13375609, rs522496
and rs2296225) of KIF17 gene in 567 schizophrenia and 710 healthy subjects was
examined. Both genotypic distribution and allelic frequency of rs2296225
polymorphism were significantly different between the chronic schizophrenia
subjects and controls. However, our findings described above were not replicated
with the independent subjects (555 schizophrenia and 814 healthy controls).
Furthermore, the two alleles of rs2296225 polymorphism did not affect the mRNA
expression of KIF17. These results suggest that the dysfunction of KIF17 might be
involved in the pathophysiology of schizophrenia.
PMID- 26421901
TI - Relationship between personality traits and perceived internalized stigma in
bipolar patients and their treatment partners.
AB - Internalized stigma of mental disorders has significant negative outcomes for
patients with bipolar disorder and their families. The aim of this study is to
evaluate the association between personality traits and internalized stigma of
mental disorders in bipolar patients and their treatment partners. Five different
questionnaires were utilized in this study: (1) Demographic data questionnaire,
(2) Millon Clinical Multiaxial Inventory-III (MCMI-III) for personality traits,
(3) Internalized Stigma of Mental Illness (ISMI) for stigma, (4) Self Report
Manic Inventory (SRMI) for mania and (5) Center for Epidemiological Studies
Depression Scale (CES-D) for depression. The scores of personality traits were
combined to create externalizing and internalizing personality trait scores.
Results showed that patients with bipolar disorder and their treatment partners
both experienced internalized stigma of mental health disorders. There was a
significant positive correlation between internalized stigma and internalizing
personality traits, but not externalizing traits. In a multi-variate regression
analysis, internalizing personality trait score was found to be a significant
predictor of internalized stigma. In conclusion, patients with bipolar disorder
and their treatment partners perceive higher level of internalized stigma of
mental disorders if they have internalizing personality traits.
PMID- 26421902
TI - A Tunable Dispersion-Free Terahertz Metadevice with Pancharatnam-Berry-Phase
Enabled Modulation and Polarization Control.
AB - It is extremely challenging to control the phase of light at will in free space.
Here, Pancharatnam-Berry-phase-enabled, tunable phase control of free-space light
is experimentally demonstrated in an ultrathin flexible dispersion-free
metadevice. This metadevice enables the broadband conversion of linearly
polarized light into any desired output polarization.
PMID- 26421903
TI - Measles Outbreak Associated with Vaccine Failure in Adults--Federated States of
Micronesia, February-August 2014.
AB - On May 15, 2014, CDC was notified of two laboratory-confirmed measles cases in
the Federated States of Micronesia (FSM), after 20 years with no reported
measles. FSM was assisted by the World Health Organization (WHO), the United
Nations Children's Fund (UNICEF), and CDC in investigating suspected cases,
identify contacts, conduct analyses to guide outbreak vaccination response, and
review vaccine cold chain practices. During February-August, three of FSM's four
states reported measles cases: Kosrae (139 cases), Pohnpei (251), and Chuuk (3).
Two thirds of cases occurred among adults aged >=20 years; of these, 49% had
received >=2 doses of measles-containing vaccine (MCV). Apart from infants aged
<12 months who were too young for routine vaccination, measles incidence was
lower among children than adults. A review of current cold chain practices in
Kosrae revealed minor weaknesses; however, an absence of historical cold chain
maintenance records precluded an evaluation of earlier problems. Each state
implemented vaccination campaigns targeting children as young as age 6 months
through adults up to age 57 years. The preponderance of cases in this outbreak
associated with vaccine failure in adults highlights the need for both thorough
case investigation and epidemiologic analysis to guide outbreak response
vaccination. Routine childhood vaccination coverage achieved in recent years
limited the transmission of measles among children. Even in areas where
transmission has not occurred for years, maintaining high 2-dose MCV coverage
through routine and supplemental immunization is needed to prevent outbreaks
resulting from increased measles susceptibility in the population.
PMID- 26421904
TI - Creation of a head and neck Keloid quality of life questionnaire.
AB - OBJECTIVES: Create a head-and-neck keloid quality of life (QOL) questionnaire.
Demonstrate the reliability of the keloid-specific QOL scale according to test
retest and internal consistency standards. STUDY DESIGN: Prospective cohort
study. METHODS: Patients presenting to a keloid clinic in a tertiary referral
institution between April 2012 and February 2013 were enrolled on their first
visit. They were administered a questionnaire assessing demographics and a 21
item Likert keloid-specific survey assessing symptomatology, self-esteem, social
functioning, and therapeutic motivation during their first three visits.
Reliability of the keloid questionnaire was assessed for internal consistency
(Cronbach's alpha) and test-retest correlations. Patients were treated with
Kenalog steroid injections at each visit. The 126-point total score from the
questionnaire was then compared to each subscale (physical symptoms, self-esteem,
social function, and medical motivation) using a Pearson coefficient. RESULTS:
The keloid QOL questionnaire showed a Cronbach's alpha of 0.87 for the overall
questionnaire and ranged from 0.66 to 0.86 for individual questions. The test
retest Pearson's R was 0.70 between visits 1 and 2 and 0.77 between visits 2 and
3. The Pearson correlation between symptoms, self-esteem, social functioning, and
medical motivation subscales and the overall scale were 0.77, 0.73, 0.72, and
0.57, respectively. CONCLUSION: This head and neck keloid-specific QOL
questionnaire proved to be a reproducible method of reliably assessing QOL burden
on patients with head and neck keloids. LEVEL OF EVIDENCE: N/A.
PMID- 26421905
TI - Psychometric properties of the Turkish version of the Internet Addiction Test
(IAT).
AB - OBJECTIVE: Of many instruments developed to assess Internet addiction, the
Internet Addiction Test (IAT), an expanded version of the Internet Addiction
Diagnostic Questionnaire (IADQ), has been the most widely used scale in English
and non-English speaking populations. In this study, our aim was to investigate
the psychometric properties of short and expanded versions of the IAT in a
Turkish undergraduate sample. METHOD: Overall, 455 undergraduate students from
Turkey aged between 18 and 30 participated in the study (63.53% were females).
Explanatory and confirmatory factor analytic procedures investigated factor
structures of the IADQ and IAT. The Internet Addiction Scale (IAS), Coping
Inventory for Stressful Situations (CISS), Obsessive Compulsive Inventory-Revised
(OCI-R) and Dissociative Experiences Scale (DES) were administered to assess
convergent and divergent validities of the IADQ and IAT. Internal consistency and
15-day test-retest reliability were computed. RESULTS: In the factorial analytic
investigation, we found a unidimensional factor structure for each measure fit
the current data best. Significant but weak to moderate correlations of the IADQ
and the IAT with the CISS, OCI-R and DES provided empirical evidence for
divergent validity, whereas strong associations with the subscales of the IAS
pointed to the convergent validity of Young's Internet addiction construct.
Internal consistency of the IADQ was weak (alpha=0.67) and of the IAT was high
(alpha=0.93). Temporal reliability of both instruments was very high (alpha=0.81
and alpha=0.87; respectively). CONCLUSION: The IAT revealed promising and sound
psychometric properties in a Turkish sample.
PMID- 26421906
TI - Reactions to Participating in Intimate Partner Violence and Minority Stress
Research: A Mixed Methodological Study of Self-Identified Lesbian and Gay
Emerging Adults.
AB - The purpose of this study was to examine lesbian and gay (LG) young adults'
reactions to participating in intimate partner violence (IPV) and minority stress
research using a mixed methodological design. Participants were 277 U.S. college
students currently involved in same-sex relationships and self-identified
cisgender LG who completed an online questionnaire that included closed- and open
ended questions. Results suggested that IPV research was well tolerated by the
vast majority of participants; close to one in 10 participants reported being
upset by the study questions, yet 75% of upset individuals reported some level of
personal benefit. Reasons for upset as identified in the open-ended responses
included thinking about personal experiences with IPV, as the perpetrator or
friend of a victim, as well as thinking about the uncertainty of their future
with their current partner. The correlates of emotional reactions and personal
benefits to research participation were also examined, and these varied among gay
men and lesbian women. Implications of these findings underscore the importance
of accurate reflection of risk and benefits in informed consent documents as well
as systematic evaluation of sexual minority participants' reactions to research
participation in an effort to conduct ethically sound sexual science research.
PMID- 26421907
TI - Single-Molecule Force Spectroscopy of an Artificial DNA Duplex Comprising a
Silver(I)-Mediated Base Pair.
AB - Single-molecule force spectroscopy measurements of a DNA duplex comprising an
artificial metal-mediated base pair are reported. The measurements reveal that
DNA duplexes comprising one central imidazole:imidazole mispair rupture at lower
forces than a related duplex with canonical base pairs only. In contrast, DNA
duplexes with one central imidazole-Ag(+)-imidazole base pair (formed by the
addition of Ag(+) to the aforementioned duplex with the mispair) rupture at
higher forces. These measurements indicate for the first time that the increase
in thermal stability of a nucleic acid duplex that is observed upon the formation
of a metal-mediated base pair is accompanied by a concomitant mechanical
stabilization. In fact, the mechanical stabilization even exceeds the thermal
one. This result indicates that nucleic acids with metal-mediated base pairs
should be ideal building blocks for rigid functionalized DNA nano-objects.
PMID- 26421908
TI - In reference to A new theory on the pathogenesis of acquired cholesteatoma:
mucosal traction.
PMID- 26421909
TI - A clinical score to rule out the concomitant presence of deep vein thrombosis in
patients presenting with superficial vein thrombosis: The ICARO study.
AB - BACKGROUND: Superficial vein thrombosis (SVT) is commonly encountered in clinical
practice. Recent studies have suggested that the concomitant presence of deep
vein thrombosis (DVT) or pulmonary embolism (PE) at the time of SVT diagnosis is
not uncommon, thus increasing the interest on this disease. Whether this
coexistence is predicted by specific risk factors remains unknown. AIM OF THE
STUDY: To evaluate potential risk factors for DVT coexistence in patients
presenting with acute objectively diagnosed SVT of the lower limbs and to develop
a simple score entirely based on clinical variables to define the pre-test
probability of DVT in these patients. METHODS: A multicenter, retrospective
cohort study on SVT patients was conducted. Information was collected on clinical
signs and on risk factors for venous thrombosis. RESULTS: 494 patients (mean age
56.3 +/- 17.9 years, 64.2% women) were included. Concomitant DVT was found in
16.0% of patients. After multivariate analysis, we identified 5 independent
variables that were used to develop the ICARO score: active malignancy (1.5
points), limb edema (1.5 points), rope-like sign (-1 point), age >= 50 years (1
point), unprovoked SVT (-1 point). The prevalence of concomitant DVT was 1.1% in
the low-probability category (< 0 points), 12.0% in the intermediate-probability
category (0 to 1 points), and 32.3% in the high probability category (>= 1.5
points). CONCLUSIONS: The concomitant presence of major DVT is not negligible in
patients with SVT. Our prediction score entirely based on simple clinical
variables may be useful in assessing the risk of concomitant DVT in these
patients.
PMID- 26421911
TI - The role of high-involvement work practices and professional self-image in
nursing recruits' turnover: A three-year prospective study.
AB - BACKGROUND: The retention of young graduate nurses has become a major management
challenge among hospitals in Western countries, which is amplified in a context
of aging of populations and an increasing demand for services from patients.
Moreover, as it has been reported that 50% of experienced nurses do not recommend
a career in nursing, it is likely that retention problems occur not only at the
level of the organization, but also at the level of the nursing profession.
Although research has identified some predictors of nurse turnover, it is unclear
which factors influence nurses' turnover from the organization and from the
profession and how these factors interrelate with one another over time.
OBJECTIVE: The present study extends previous research on nurse turnover by
looking at the combined effects of nurses' pre-entry expectations, perceived high
involvement work practices, and professional self-image, on intended and actual
turnover from the organization and the profession. DESIGN AND METHODS: A
prospective, longitudinal study of a sample of 160 graduated nurses affiliated
with the Quebec Nurses' Association, Canada, was conducted. Participants were
surveyed at three points in time, spread over a 3-year period. Graduated nurses'
pre-entry expectations and professional self-image were surveyed at graduation
(Time 1), while perceived high-involvement work practices, professional self
image, and intention to leave the organization and the profession were captured
six months following nurses' entry into the labor market (Time 2). Finally,
participants were surveyed with respect to organizational and professional
turnover three years after the Time 2 survey (Time 3). Structural equations
modeling was used to examine the structure of the measures and the relationships
among the constructs. RESULTS: Although pre-entry expectations had no effect,
perceived high-involvement work practices were positively related to Time 2,
professional self-image (controlling for pre-entry professional self-image).
Moreover, high-involvement work practices exerted an indirect, negative effect on
organizational and professional turnover through intention to leave the
organization, and an indirect negative effect on intention to leave the
profession through professional self-image. Nonetheless, professional self-image
did not affect turnover. CONCLUSIONS: The current study indicates that hospitals
and nurse directors can take advantage of developing high-involvement work
practices as these practices foster a stronger professional self-image among
nurses, thereby contributing to their sense of value as care providers, and
indirectly reduce intended and actual turnover from the organization and the
profession.
PMID- 26421910
TI - Impact of a person-centred dementia care training programme on hospital staff
attitudes, role efficacy and perceptions of caring for people with dementia: A
repeated measures study.
AB - BACKGROUND: People with dementia occupy up to one quarter of acute hospital beds.
However, the quality of care delivered to this patient group is of national
concern. Staff working in acute hospitals report lack of knowledge, skills and
confidence in caring for people with dementia. There is limited evidence about
the most effective approaches to supporting acute hospital staff to deliver more
person-centred care. OBJECTIVES: This study aimed to evaluate the efficacy of a
specialist training programme for acute hospital staff regarding improving
attitudes, satisfaction and feelings of caring efficacy, in provision of care to
people with dementia. DESIGN: A repeated measures design, with measures completed
immediately prior to commencing training (T1), after completion of Foundation
level training (T2: 4-6 weeks post-baseline), and following Intermediate level
training (T3: 3-4 months post-baseline). SETTING: One NHS Trust in the North of
England, UK. PARTICIPANTS: 40 acute hospital staff working in clinical roles, the
majority of whom (90%) were nurses. METHODS: All participants received the 3.5
day Person-centred Care Training for Acute Hospitals (PCTAH) programme, comprised
of two levels, Foundation (0.5 day) and Intermediate (3 days), delivered over a 3
4 months period. Staff demographics and previous exposure to dementia training
were collected via a questionnaire. Staff attitudes were measured using the
Approaches to Dementia Questionnaire (ADQ), satisfaction in caring for people
with dementia was captured using the Staff Experiences of Working with Demented
Residents questionnaire (SEWDR) and perceived caring efficacy was measured using
the Caring Efficacy Scale (CES). RESULTS: The training programme was effective in
producing a significant positive change on all three outcome measures following
intermediate training compared to baseline. A significant positive effect was
found on the ADQ between baseline and after completion of Foundation level
training, but not for either of the other measures. CONCLUSIONS: Training acute
hospital staff in Intermediate level person-centred dementia care is effective in
producing significant improvements in attitudes towards and satisfaction in
caring for people with dementia and feelings of caring efficacy. Foundation level
training is effective in changing attitudes but does not seem to be sufficient to
bring about change in satisfaction or caring efficacy.
PMID- 26421912
TI - The influence of hormone therapies on type I and II endometrial cancer: A
nationwide cohort study.
AB - The influence of hormone therapy (HT) on risk for endometrial cancer is still
casting which type of HT the clinicians recommend. It is unrevealed if HT has a
differential influence on Type I versus Type II endometrial tumors, and little is
known about the influence of, e.g., different routes of administration and about
the influence of tibolone. We followed all Danish women aged 50-79 years without
previous cancer or hysterectomy (n = 914,595) during 1995-2009. From the National
Prescription Register, we computed HT exposures as time-dependent covariates.
Incident endometrial cancers (n = 6,202) were identified from the National Cancer
Registry: 4,972 Type I tumors and 500 Type II tumors. Incidence rate ratios (RRs)
and 95% confidence intervals (Cls) were estimated by Poisson regression. Compared
with women never on HT, the RR of endometrial cancer was increased with
conjugated estrogen: 4.27 (1.92-9.52), nonconjugated estrogen: 2.00 (1.87-2.13),
long cycle combined therapy: 2.89 (2.27-3.67), cyclic combined therapy: 2.06
(1.88-2.27), tibolone 3.56 (2.94-4.32), transdermal estrogen: 2.77 (2.12-3.62)
and vaginal estrogen: 1.96 (1.77-2.17), but not with continuous combined therapy:
1.02 (0.87-1.20). In contrast, the risk of Type II tumors appeared decreased with
continuous combined therapy: 0.45 (0.20-1.01), and estrogen therapy implied a
nonsignificantly altered risk of 1.43 (0.85-2.41). Our findings support that
continuous combined therapy is risk free for Type I tumors, while all other
hormone therapies increase risk. In contrast, Type II endometrial cancer was less
convincingly associated with hormone use, and continuous combined therapy
appeared to decrease the risk.
PMID- 26421913
TI - A (210)Pb-based chronological model for recent sediments with random entries of
mass and activities: Model development.
AB - Unsupported (210)Pb ((210)Pbexc) vs. mass depth profiles do not contain enough
information as to extract a unique chronology when both, (210)Pbexc fluxes and
mass sediment accumulation rates (SAR) independently vary with time. Restrictive
assumptions are needed to develop a suitable dating tool. A statistical
correlation between fluxes and SAR seems to be a quite general rule. This paper
builds up a new (210)Pb-based dating tool by using such a statistical
correlation. It operates with SAR and initial activities that closely follow
normal distributions, what leads to the expected correlation between fluxes and
SAR. An intelligent algorithm solves their best arrangement downcore to fit the
experimental (210)Pbexc vs. mass depth profile, generating then solutions for the
chronological line, and for the histories of SAR and fluxes. Parametric maps of a
chi-function serve to find out the solution and to support error estimates.
Optionally, the model's answers can be better constrained through the use of time
markers. The performance of the model is illustrated with a synthetic core, and
with real cases using published data for varved sediment cores.
PMID- 26421914
TI - Children With ADHD Show Impairments in Multiple Stages of Information Processing
in a Stroop Task: An ERP Study.
AB - This study investigated the role of impaired inhibitory control as a factor
underlying attention deficit hyperactivity disorder (ADHD). Children with ADHD
and typically developing children completed an animal Stroop task while
electroencephalogram (EEG) was recorded. The lateralized readiness potential and
event-related brain potentials associated with perceptual and conflict processing
were analyzed. Children with ADHD were slower to give correct responses
irrespective of congruency, and slower to prepare correct responses in the
incongruent condition. This delay could result from enhanced effort allocation at
earlier processing stages, indicated by differences in P1, N1, and conflict
sustained potential. Results suggest multiple deficits in information processing
rather than a specific response inhibition impairment.
PMID- 26421915
TI - Photochemical Oxidation of Thioketones by Singlet Molecular Oxygen Revisited:
Insights into Photoproducts, Kinetics, and Reaction Mechanism.
AB - Photosensitized oxidation of trimethyl[2.2.1]bicycloheptane thioketones by (1)O2
can yield more photoproducts than exclusively ketones and sulfines. Moreover, the
ketone/sulfine ratio can be reversed when protic conditions and high thioketone
concentrations are used, conversely to earlier results reporting ketones as the
main photoproducts. A new mechanistic proposal for sulfine formation is suggested
following intermolecular oxygen transfer from a peroxythiocarbonyl intermediate
to a second thioketone molecule. Reaction quantum yields (10(-5)-10(-2)) depend
on the reaction conditions and time. Sulfine production reaches a maximum at
short irradiation times, whereas decomposition to the corresponding ketone is
observed at long reaction times. When the thioketone substrate has a hydrogen
atom at the alpha position a peroxyvinylsulfenic acid intermediate can be formed
by proton transfer. Reaction of this intermediate with another thioketone
molecule can yield more sulfine and its tautomeric vinylsulfenic acid, which
dimerizes in situ to the thiosulfinate. The hydroperoxyl group of the
peroxyvinylsulfenic acid can also rearrange to the alpha position, and by
reaction with the starting thioketone, alpha-hydroxy thioketone and additional
sulfine can be formed, while dehydration yields the alpha-oxo thioketone. In situ
[2 + 2] and [4 + 2] self-cycloaddition of the alpha-oxo thioketone yields
significant amounts of the corresponding adducts at prolonged irradiation times.
PMID- 26421916
TI - Layer-by-layer assembly for biomedical applications in the last decade.
AB - In the past two decades, the design and manufacture of nanostructured materials
has been of tremendous interest to the scientific community for their application
in the biomedical field. Among the available techniques, layer-by-layer (LBL)
assembly has attracted considerable attention as a convenient method to fabricate
functional coatings. Nowadays, more than 1000 scientific papers are published
every year, tens of patents have been deposited and some commercial products
based on LBL technology have become commercially available. LBL presents several
advantages, such as (1): a precise control of the coating properties; (2)
environmentally friendly, mild conditions and low-cost manufacturing; (3)
versatility for coating all available surfaces; (4) obtainment of homogeneous
film with controlled thickness; and (5) incorporation and controlled release of
biomolecules/drugs. This paper critically reviews the scientific challenge of the
last 10 years--functionalizing biomaterials by LBL to obtain appropriate
properties for biomedical applications, in particular in tissue engineering (TE).
The analysis of the state-of-the-art highlights the current techniques and the
innovative materials for scaffold and medical device preparation that are opening
the way for the preparation of LBL-functionalized substrates capable of modifying
their surface properties for modulating cell interaction to improve substitution,
repair or enhancement of tissue function.
PMID- 26421917
TI - Mechanism of One-to-Many Molecular Recognition Accompanying Target-Dependent
Structure Formation: For the Tumor Suppressor p53 Protein as an Example.
AB - The new type of molecular recognition, in which an intrinsically disordered
region (IDR) of a protein binds to many different target proteins with target
dependent structure formation, is indispensable to the expression of life
phenomena and also implicated in a number of diseases. According to the
prevailing view, the physicochemical factors responsible for the binding are also
target dependent. Here we consider an IDR of the tumor suppressor p53 protein,
p53CTD, as an important example related to carcinogenesis and analyze its binding
to four targets accompanying the formation of target-dependent structures (i.e.,
helix, sheet, and two different coils) using our statistical-mechanical method
combined with molecular models for water. We find that all of the seemingly
different binding processes are driven by a large gain of the translational,
configurational entropy of water in the system. The gain originates from
sufficiently high shape complementarity on the atomic level within the p53CTD
target interface. It is also required that the electrostatic complementarity be
ensured as much as possible to compensate for the dehydration. Such
complementarities are achieved in harmony with the portion of the target to which
p53CTD binds, leading to a large diversity of structures of p53CTD formed upon
binding: If they are not achievable, the binding does not occur. This finding is
made possible only by calculating the changes in thermodynamic quantities upon
binding and decomposing them into physically insightful components.
PMID- 26421918
TI - Genome-Wide Analysis and Expression Profiling of the Phospholipase C Gene Family
in Soybean (Glycine max).
AB - Phosphatidylinositol-specific phospholipase C (PI-PLC) hydrolyses
phosphatidylinositol-4,5-bisphosphate to produce diacylglycerol and inositol
1,4,5-trisphosphate. It plays an important role in plant development and abiotic
stress responses. However, systematic analysis and expression profiling of the
phospholipase C (PLC) gene family in soybean have not been reported. In this
study, 12 putative PLC genes were identified in the soybean genome. Soybean PLCs
were found on chromosomes 2, 11, 14 and 18 and encoded 58.8-70.06 kD proteins.
Expression pattern analysis by RT-PCR demonstrated that expression of the GmPLCs
was induced by PEG, NaCl and saline-alkali treatments in roots and leaves. GmPLC
transcripts accumulated specifically in roots after ABA treatment. Furthermore,
GmPLC transcripts were analyzed in various tissues. The results showed that
GmPLC7 was highly expressed in most tissues, whereas GmPLC12 was expressed in
early pods specifically. In addition, subcellular localization analysis was
carried out and confirmed that GmPLC10 was localized in the plasma membrane in
Nicotiana benthamiana. Our genomic analysis of the soybean PLC family provides an
insight into the regulation of abiotic stress responses and development. It also
provides a solid foundation for the functional characterization of the soybean
PLC gene family.
PMID- 26421919
TI - Association of High-Resolution Manometry Metrics with the Symptoms of Achalasia
and the Symptomatic Outcomes of Peroral Esophageal Myotomy.
AB - BACKGROUND: High-resolution manometry (HRM) has improved the accuracy of
manometry in detecting achalasia and has helped distinguish between clinically
relevant subtypes. This study investigated whether HRM metrics correlate with the
achalasia symptoms and symptomatic outcomes of peroral esophageal myotomy (POEM).
METHODS: Of the 30 patients who were enrolled, 25 were treated with POEM, 12 of
who underwent HRM after 3 months. All the patients completed the Eckardt score
questionnaires, and those who underwent POEM were followed up for about 6 months.
Pearson correlation was used to assess the relationship between the HRM metrics
and symptoms and outcomes. KEY RESULTS: The integrated relaxation pressure (IRP)
score positively correlated with the total Eckardt score, regurgitation score and
weight loss score in all the patients, and with the weight loss score in type I
achalasia. In 25 patients (10 patients, type I; 15 patients, type II) who
underwent POEM, the total Eckardt scores and individual symptom scores
significantly decreased after surgery. Changes in the Eckardt scores were similar
between type I and type II. Further, the Eckardt scores and weight loss score
changes were positively correlated with baseline IRP. Twelve patients (4
patients, type I; 8 patients, type II) underwent HRM again after POEM. IRP
changed significantly after POEM, as did the DEP in type II. The IRP changes
after POEM were positively correlated with the Eckardt score changes. CONCLUSIONS
& INFERENCES: IRP is correlated with the symptoms and outcomes of achalasia
patients. Thus, HRM is effective for assessing the severity of achalasia and can
predict the efficacy of POEM.
PMID- 26421920
TI - A Simple "Blood-Saving Bundle" Reduces Diagnostic Blood Loss and the Transfusion
Rate in Mechanically Ventilated Patients.
AB - INTRODUCTION: Aim of this study was to reduce blood loss caused by diagnostic
blood sampling and to minimize the development of anemia in a high-risk group of
mechanically ventilated medical intensive care patients. We therefore implemented
a "blood-saving bundle" (BSB) combining a closed-loop arterial blood sampling
system, smaller sampling tubes, reduced frequency of blood drawings, and reduced
sample numbers. METHODS: The study included all patients from our medical ICU who
were ventilated for more than 72 hours. Exclusion criteria were: acute or chronic
anemia on admission, bleeding episode(s) during the ICU stay, or end-of-life
therapy. The BSB was introduced in 2009 with training and educational support.
Patients treated in 2008, before the introduction of the BSB, served as a control
group (n = 41, 617 observation days), and were compared with patients treated in
2010 after the introduction of the BSB (BSB group, n = 50, 559 observation days).
Primary endpoints were blood loss per day, and development of anemia. Secondary
endpoints were numbers of blood transfusions, number of days on mechanical
ventilation, and length of the ICU stay. RESULTS: Mean blood loss per ICU day was
decreased from 43.3 ml (95% CI: 41.2 to 45.3 ml) in the controls to 15.0 ml (14.3
to 15.7 ml) in the BSB group (P < 0.001). The introduction of a closed-loop
arterial blood sampling system was the major contributor to this effect. Mean
hemoglobin concentrations showed no significant differences in both groups during
the ICU stay. Hemoglobin values <9 g/dl, however, were recorded in 21.2% of
observation days in the controls versus 15.4% in the BSB group (P = 0.01). Units
of transfused red blood cells per 100 observation days decreased from 7 to 2.3 (P
< 0.001). The mean number of ventilation days was 7.1 days (6.1 to 8.3 days) in
the controls and 7.5 days (6.6 to 8.5 days) in the BSB group (P = NS). In total,
patients in the BSB group stayed in ICU for a mean of 9.9 days (8.6 to 11.3
days), compared to a mean ICU stay of 13.0 days (10.9 to 15.4 days) in the
control group (P = 0.014). Due to the longitudinal study design, however, we
cannot exclude uncontrolled confounders affecting the transfusion frequency and
mean ICU stay. CONCLUSION: Our BSB could be easily implemented and was able to
reduce diagnostic blood loss.
PMID- 26421921
TI - Design, Synthesis, and Pharmacological Evaluation of 5,6-Disubstituted Pyridin
2(1H)-one Derivatives as Phosphodiesterase 10A (PDE10A) Antagonists.
AB - We report the design and synthesis of novel 5,6-diarylated pyridin-2(1H)-one
derivatives as pharmacophoric PDE10A inhibitors. This highly potent molecular
scaffold was developed from an inactive diarylpyridine-2-amine derivative 3b by
extensive and systematic analogue synthesis and SAR analysis. Further
optimization of the scaffold resulted in identification of pyridin-2(1H)-one 18b
as a lead compound with good potency (IC50 = 1.6 nM) and selectivity (>6000-fold)
over other related PDEs but with a poor pharmacokinetic profile. Careful
metabolite profiling of 18b revealed that poor systemic exposure in rats (Cmax =
44 ng/mL; AUC0-t = 359 ng . h/mL) at 10 mg/kg was due to the formation of O
glucuronide conjugate by phase 2 metabolism. The structure of the glucuronide
metabolite was confirmed by retention time and LC-MS/MS fragmentation matching
with the synthetic glucuronide 26. The problem of low exposure of 18b was
effectively addressed by its conversion to an acetate prodrug 25b, which upon
oral dosing resulted in an improved pharmacokinetic profile (Cmax = 359 ng.h/mL;
AUC0-t = 2436 ng.h/mL) and a desirable brain to plasma ratio of 1.2. The prodrug
25b showed good efficacy in selected rodent models of psychosis.
PMID- 26421922
TI - Endocytosed 2-Microglobulin Amyloid Fibrils Induce Necrosis and Apoptosis of
Rabbit Synovial Fibroblasts by Disrupting Endosomal/Lysosomal Membranes: A Novel
Mechanism on the Cytotoxicity of Amyloid Fibrils.
AB - Dialysis-related amyloidosis is a major complication in long-term hemodialysis
patients. In dialysis-related amyloidosis, beta2-microglobulin (beta2-m) amyloid
fibrils deposit in the osteoarticular tissue, leading to carpal tunnel syndrome
and destructive arthropathy with cystic bone lesions, but the mechanism by which
these amyloid fibrils destruct bone and joint tissue is not fully understood. In
this study, we assessed the cytotoxic effect of beta2-m amyloid fibrils on the
cultured rabbit synovial fibroblasts. Under light microscopy, the cells treated
with amyloid fibrils exhibited both necrotic and apoptotic changes, while the
cells treated with beta2-m monomers and vehicle buffer exhibited no morphological
changes. As compared to beta2-m monomers and vehicle buffer, beta2-m amyloid
fibrils significantly reduced cellular viability as measured by the lactate
dehydrogenase release assay and the 3-(4,5-di-methylthiazol-2-yl)-2,5
diphenyltetrazolium bromide reduction assay and significantly increased the
percentage of apoptotic cells as measured by the terminal deoxynucleotidyl
transferase-mediated dUTP nick end labeling method. beta2-m amyloid fibrils added
to the medium adhered to cell surfaces, but did not disrupt artificial plasma
membranes as measured by the liposome dye release assay. Interestingly, when the
cells were incubated with amyloid fibrils for several hours, many
endosomes/lysosomes filled with amyloid fibrils were observed under confocal
laser microscopy and electron microscopy, Moreover, some endosomal/lysosomal
membranes were disrupted by intravesicular fibrils, leading to the leakage of the
fibrils into the cytosol and adjacent to mitochondria. Inhibition of actin
dependent endocytosis by cytochalasin D attenuated the toxicity of amyloid
fibrils. These results suggest that endocytosed beta2-m amyloid fibrils induce
necrosis and apoptosis by disrupting endosomal/lysosomal membranes, and this
novel mechanism on the cytotoxicity of amyloid fibrils is described.
PMID- 26421923
TI - Extensive Hair-Shaft Elongation by Isolated Mouse Whisker Follicles in Very Long
Term Gelfoam(r) Histoculture.
AB - We have previously studied mouse whisker follicles in Gelfoam(r) histoculture to
determine the role of nestin-expressing plutipotent stem cells, located within
the follicle, in the growth of the follicular sensory nerve. Long-term Gelfoam(r)
whisker histoculture enabled hair follicle nestin-expressing stem cells to
promote the extensive elongation of the whisker sensory nerve, which contained
axon fibers. Transgenic mice in which the nestin promoter drives green
fluorescent protein (ND-GFP) were used as the source of the whiskers allowing
imaging of the nestin-expressing stem cells as they formed the follicular sensory
nerve. In the present report, we show that Gelfoam(r)-histocultured whisker
follicles produced growing pigmented and unpigmented hair shafts. Hair-shaft
length increased rapidly by day-4 and continued growing until at least day-12
after which the hair-shaft length was constant. By day-63 in histoculture, the
number of ND-GFP hair follicle stem cells increased significantly and the
follicles were intact. The present study shows that Gelfoam(r) histoculture can
support extensive hair-shaft growth as well as hair follicle sensory-nerve growth
from isolated hair follicles which were maintained over very long periods of
time. Gelfoam(r) histoculture of hair follicles can provide a very long-term
period for evaluating novel agents to promote hair growth.
PMID- 26421924
TI - Conserved Motifs within Hepatitis C Virus Envelope (E2) RNA and Protein
Independently Inhibit T Cell Activation.
AB - T cell receptor (TCR) signaling is required for T-cell activation, proliferation,
differentiation, and effector function. Hepatitis C virus (HCV) infection is
associated with impaired T-cell function leading to persistent viremia, delayed
and inconsistent antibody responses, and mild immune dysfunction. Although
multiple factors appear to contribute to T-cell dysfunction, a role for HCV
particles in this process has not been identified. Here, we show that incubation
of primary human CD4+ and CD8+ T-cells with HCV RNA-containing serum, HCV-RNA
containing extracellular vesicles (EVs), cell culture derived HCV particles
(HCVcc) and HCV envelope pseudotyped retrovirus particles (HCVpp) inhibited TCR
mediated signaling. Since HCVpp's contain only E1 and E2, we examined the effect
of HCV E2 on TCR signaling pathways. HCV E2 expression recapitulated HCV particle
induced TCR inhibition. A highly conserved, 51 nucleotide (nt) RNA sequence was
sufficient to inhibit TCR signaling. Cells expressing the HCV E2 coding RNA
contained a short, virus-derived RNA predicted to be a Dicer substrate, which
targeted a phosphatase involved in Src-kinase signaling (PTPRE). T-cells and
hepatocytes containing HCV E2 RNA had reduced PTPRE protein levels. Mutation of 6
nts abolished the predicted Dicer interactions and restored PTPRE expression and
proximal TCR signaling. HCV RNA did not inhibit distal TCR signaling induced by
PMA and Ionomycin; however, HCV E2 protein inhibited distal TCR signaling. This
inhibition required lymphocyte-specific tyrosine kinase (Lck). Lck phosphorylated
HCV E2 at a conserved tyrosine (Y613), and phospho-E2 inhibited nuclear
translocation of NFAT. Mutation of Y613 restored distal TCR signaling, even in
the context of HCVpps. Thus, HCV particles delivered viral RNA and E2 protein to
T-cells, and these inhibited proximal and distal TCR signaling respectively.
These effects of HCV particles likely aid in establishing infection and
contribute to viral persistence.
PMID- 26421925
TI - Dynamic FDG-PET Imaging to Differentiate Malignancies from Inflammation in
Subcutaneous and In Situ Mouse Model for Non-Small Cell Lung Carcinoma (NSCLC).
AB - BACKGROUND: [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)
has been widely used in oncologic procedures such as tumor diagnosis and staging.
However, false-positive rates have been high, unacceptable and mainly caused by
inflammatory lesions. Misinterpretations take place especially when non
subcutaneous inflammations appear at the tumor site, for instance in the lung.
The aim of the current study is to evaluate the use of dynamic PET imaging
procedure to differentiate in situ and subcutaneous non-small cell lung carcinoma
(NSCLC) from inflammation, and estimate the kinetics of inflammations in various
locations. METHODS: Dynamic FDG-PET was performed on 33 female mice inoculated
with tumor and/or inflammation subcutaneously or inside the lung. Standardized
Uptake Values (SUVs) from static imaging (SUVmax) as well as values of influx
rate constant (Ki) of compartmental modeling from dynamic imaging were obtained.
Static and kinetic data from different lesions (tumor and inflammations) or
different locations (subcutaneous, in situ and spontaneous group) were compared.
RESULTS: Values of SUVmax showed significant difference in subcutaneous tumor and
inflammation (p<0.01), and in inflammations from different locations (p<0.005).
However, SUVmax showed no statistical difference between in situ tumor and
inflammation (p = 1.0) and among tumors from different locations (subcutaneous
and in situ, p = 0.91). Values of Ki calculated from compartmental modeling
showed significant difference between tumor and inflammation both subcutaneously
(p<0.005) and orthotopically (p<0.01). Ki showed also location specific values
for inflammations (subcutaneous, in situ and spontaneous, p<0.015). However, Ki
of tumors from different locations (subcutaneous and in situ) showed no
significant difference (p = 0.46). CONCLUSION: In contrast to static PET based
SUVmax, both subcutaneous and in situ inflammations and malignancies can be
differentiated via dynamic FDG-PET based Ki. Moreover, Values of influx rate
constant Ki from compartmental modeling can offer an assessment for inflammations
at different locations of the body, which also implies further validation is
necessary before the replacement of in situ inflammation with its subcutaneous
counterpart in animal experiments.
PMID- 26421926
TI - Exploiting Human Resource Requirements to Infer Human Movement Patterns for Use
in Modelling Disease Transmission Systems: An Example from Eastern Province,
Zambia.
AB - In this research, an agent-based model (ABM) was developed to generate human
movement routes between homes and water resources in a rural setting, given
commonly available geospatial datasets on population distribution, land cover and
landscape resources. ABMs are an object-oriented computational approach to
modelling a system, focusing on the interactions of autonomous agents, and aiming
to assess the impact of these agents and their interactions on the system as a
whole. An A* pathfinding algorithm was implemented to produce walking routes,
given data on the terrain in the area. A* is an extension of Dijkstra's algorithm
with an enhanced time performance through the use of heuristics. In this example,
it was possible to impute daily activity movement patterns to the water resource
for all villages in a 75 km long study transect across the Luangwa Valley,
Zambia, and the simulated human movements were statistically similar to empirical
observations on travel times to the water resource (Chi-squared, 95% confidence
interval). This indicates that it is possible to produce realistic data regarding
human movements without costly measurement as is commonly achieved, for example,
through GPS, or retrospective or real-time diaries. The approach is transferable
between different geographical locations, and the product can be useful in
providing an insight into human movement patterns, and therefore has use in many
human exposure-related applications, specifically epidemiological research in
rural areas, where spatial heterogeneity in the disease landscape, and space-time
proximity of individuals, can play a crucial role in disease spread.
PMID- 26421927
TI - Methicillin Resistant Staphylococcus aureus among HIV Infected Pediatric Patients
in Northwest Ethiopia: Carriage Rates and Antibiotic Co-Resistance Profiles.
AB - BACKGROUND: MRSA infections are becoming more prevalent throughout the HIV
community. MRSA infections are a challenge to both physicians and patients due to
limited choice of therapeutic options and increased cost of care. OBJECTIVES:
This study was aimed to determine the prevalence of colonization and co
resistance patterns of MRSA species among HIV positive pediatric patients in the
Amhara National Regional State, Northwest Ethiopia. METHODS: Culture swabs were
collected from the anterior nares, the skin and the perineum of 400 participants.
In vitro antimicrobial susceptibility testing was done on Muller Hinton Agar by
the Kirby-Bauer disk diffusion method, using 30 MUg cefoxitin (OXOID, ENGLAND)
according to the recommendations of the Clinical and Laboratory Standards
Institute. Methicillin sensitivity/resistance was tested using cefoxitin. Data
was analyzed by descriptive statistics and logistic regression model using Epi
Info 7. RESULTS: S. aureus was detected in 206 participants (51.5%). The
prevalence of MRSA colonization in this study was 16.8%. Colonization by S.
aureus was associated with male gender (OR = 0.5869; 95% CI: 0.3812-0.9036; p
value = 0.0155), history of antibiotic use over the previous 3 months (OR =
2.3126; 95% CI: 1.0707-4.9948; p-value = 0.0329) and having CD4 T-cell counts of
more than 350 x 10(6) cells / L (OR = 0.5739; 95% CI = 0.3343-0.9851; p-value =
0.0440). Colonization by MRSA was not associated with any one of the variables.
Concomitant resistance of the MRSA to clindamycin, chloramphenicol, co
trimoxazole, ceftriaxone, erythromycin and tetracycline was 7.6%, 6%, 5.25%,
20.9%, 23.9% and 72.1%, respectively. CONCLUSION: High rates of colonization by
pathogenic MRSA strains is observed among HIV positive pediatric patients in the
Amhara National Regional state.
PMID- 26421928
TI - Survival Tactics and Strategies of Methamphetamine-Using HIV-Positive Men Who
Have Sex with Men in San Diego.
AB - In this article, two ways that HIV-positive drug users survive under the
supervision of law enforcement agencies, community health organizations, and
social welfare offices are differentiated. First, strategies are long-ranging and
often carefully planned, and they involve conscious utilization and manipulation
of bureaucratic processes. Second, tactics are short-ranging and often haphazard,
and they are used to survive on daily or weekly bases, with entrenched problems
and structural solutions avoided or ignored. Data from three years of
ethnographic fieldwork with 14 methamphetamine-using HIV-positive men who have
sex with men in San Diego, California is used to expand upon these two
categories, explaining the different, often ineffectual, ways these men accessed
care, services, shelter, drugs, and companionship. This article also examines the
policy implications of taking in consideration these different kinds of survival
methods, arguing for intensive client-specific interventions when working with
long-term addicts with multiple health problems.
PMID- 26421929
TI - A 1-year videoconferencing-based psychoeducational group intervention following
bariatric surgery: results of a randomized controlled study.
AB - BACKGROUND: For severely obese patients, bariatric surgery has been recommended
as an effective therapy. OBJECTIVES: The Bariataric Surgery and Education (BaSE)
study aimed to assess the efficacy of a videoconferencing-based psychoeducational
group intervention in patients after bariatric surgery. SETTING: The BaSE study
is a randomized, controlled multicenter clinical trial involving 117 patients
undergoing bariatric surgery (mean preoperative body mass index [BMI] 49.9
kg/m(2), SD 6.4). Patients were enrolled between May 2009 and November 2012 and
were randomly assigned to receive either conventional postsurgical visits or, in
addition, a videoconferencing-based 1-year group program. METHODS: Primary
outcome measures were weight in kilograms, health-related quality of life
(HRQOL), and general self-efficacy (GSE). Secondary outcome measures were
depression symptoms and eating behavior. RESULTS: 94% of the patients completed
the study. Mean weight loss for all patients was 45.9 kg (SD 16.4) 1 year after
surgery (mean excess weight loss [EWL] 63%). Intention-to-treat analyses revealed
no differences in weight loss, EWL, HRQOL, or self-efficacy between study groups
at 1 year after surgery. However, patients with clinically significant depression
symptoms (CSD) at baseline assigned to the intervention group (n = 29) had a
significantly better HRQOL (P = .03), lower depression scores (P = .02), and a
trend for a better EWL (.06) 1 year after surgery compared with the control group
(n = 20). CONCLUSION: We could not prove the efficacy of the group program for
the whole study sample. However, results indicate that the intervention is
effective for the important subgroup of patients with CSD.
PMID- 26421931
TI - How to deal with the "Gordian knot" of evidence base?
PMID- 26421930
TI - Trends of Mycobacterium bovis Isolation and First-Line Anti-tuberculosis Drug
Susceptibility Profile: A Fifteen-Year Laboratory-Based Surveillance.
AB - BACKGROUND: Mycobacterium tuberculosis causes the majority of tuberculosis (TB)
cases in humans; however, in developing countries, human TB caused by M. bovis
may be frequent but undetected. Human TB caused by M. bovis is considered a
zoonosis; transmission is mainly through consumption of unpasteurized dairy
products, and it is less frequently attributed to animal-to-human or human-to
human contact. We describe the trends of M. bovis isolation from human samples
and first-line drug susceptibility during a 15-year period in a referral
laboratory located in a tertiary care hospital in Mexico City.
METHODOLOGY/PRINCIPAL FINDINGS: Data on mycobacterial isolates from human
clinical samples were retrieved from the laboratory's database for the 2000-2014
period. Susceptibility to first-line drugs: rifampin, isoniazid, streptomycin
(STR) and ethambutol was determined. We identified 1,165 isolates, 73.7% were M.
tuberculosis and 26.2%, M. bovis. Among pulmonary samples, 16.6% were M. bovis.
The proportion of M. bovis isolates significantly increased from 7.8% in 2000 to
28.4% in 2014 (X(2)trend, p<0.001). Primary STR resistance was higher among M.
bovis compared with M. tuberculosis isolates (10.9% vs.3.4%, p<0.001). Secondary
multidrug resistance (MDR) rates were 38.5% and 34.4% for M. bovis and M.
tuberculosis, respectively (p = 0.637). A rising trend of primary STR
monoresistance was observed for both species (3.4% in 2000-2004 vs. 7.6% in 2010
2014; p = 0.02). CONCLUSIONS/SIGNIFICANCE: There is a high prevalence and a
rising trend of M. bovis isolates in our region. The proportion of pulmonary M.
bovis isolates is higher than in previous reports. Additionally, we report high
rates of primary anti-tuberculosis resistance and secondary MDR in both M.
tuberculosis and M. bovis. This is one of the largest reports on drug
susceptibility of M. bovis from human samples and shows a significant proportion
of first-line anti-tuberculosis drug resistance.
PMID- 26421932
TI - A lack of evidence for neurophysiological intraoperative monitoring?
PMID- 26421933
TI - Glycan-Dependent Mutual and Reversible Sequestration of Two Thyroid Cancer
Biomarkers.
AB - BACKGROUND: Thyroglobulin (Tg), the major thyroidal protein, plays important
roles in thyroid hormone biosynthesis and in autoimmune thyroid diseases (AITD).
Tg also serves as a pre- and postoperative biomarker of differentiated thyroid
cancer (DTC). The endogenous beta-galactoside binding lectin galectin-3 (Gal-3),
secreted by transformed thyroid cells, has been shown to be another useful
biomarker of DTC. Tg contains covalently linked complex-type glycans that can
serve as binding epitopes of Gal-3. The objective of the study is to investigate
the interaction between Tg and Gal-3 and discuss its potential consequences.
METHODS: Binding interaction between Tg and Gal-3 was first studied by
hemagglutination inhibition assays. Subsequently, a detailed analysis of binding
thermodynamics was carried out by isothermal titration calorimetry. Quantitative
precipitation was performed to study the complex formation between Tg and Gal-3
and to determine the binding stoichiometry. The concentration-dependent rate and
amount of complex formation between Tg and Gal-3 was examined
spectrophotometrically. A similar approach was taken to study the effect of free
Tg and Gal-3 on preformed Tg-Gal-3 complex. RESULTS: Quantitative biochemical and
biophysical data show that these two biomarkers produced by thyroid cancer cells
interact with each other with submicromolar affinity and form an insoluble
complex at their stoichiometric concentration. One Tg molecule could bind up to
14 molecules of Gal-3. Such complex formation mutually sequestered both Tg and
Gal-3, decreasing the concentration of their freely available forms. Formation of
the Tg-Gal-3 complex was reversible as the preformed complex was dissolved by
free Tg as well as free Gal-3. While free Tg rapidly dissolved preformed Tg-Gal-3
complex in a concentration-dependent manner, Gal-3 was found to be much less
efficient and slowly dissolved only a fraction of the preformed complex at a
relatively higher Gal-3 concentration. CONCLUSIONS: Complex formation between Tg
and Gal-3 through high affinity binding and the sensitivity of the complex to
free Tg and Gal-3 can potentially influence their biological functions.
Interactions between Tg and Gal-3 might also interfere with their clinical
detection, the same way Tg autoantibody (TgAb) is reported to interfere with Tg
assays. The data support a model of Gal-3-mediated homeostatic process of Tg.
PMID- 26421934
TI - Association of interleukin-10 levels with age of onset and duration of illness in
patients with major depressive disorder.
AB - OBJECTIVE: To investigate peripheral levels of interleukin-10 (IL-10) in patients
with major depressive disorder (MDD) and bipolar disorder (BD) and evaluate the
relationship between IL-10, age of disease onset, and duration of illness.
METHODS: Case-control study nested in a population-based cohort of 231
individuals (age 18-24 years) living in Pelotas, state of Rio Grande do Sul,
Brazil. Participants were screened for psychopathology using the Mini
International Neuropsychiatric Interview (MINI) and the Structured Clinical
Interview for DSM-IV (SCID-I). Serum IL-10 was measured using commercially
available immunoassay kits. RESULTS: Peripheral levels of IL-10 were not
significantly different in individuals with MDD or BD as compared to controls.
However, higher IL-10 levels were found in MDD patients with a later disease
onset as compared with controls or early-onset patients. In addition, IL-10
levels correlated negatively with illness duration in the MDD group. In the BD
group, age of onset and duration of illness did not correlate with IL-10 levels.
CONCLUSION: Higher levels of IL-10 are correlated with late onset of MDD
symptoms. Moreover, levels of this cytokine might decrease with disease
progression, suggesting that an anti-inflammatory balance may be involved in the
onset of depressive symptoms and disease progression in susceptible individuals.
PMID- 26421935
TI - Serpentine diffusion trajectories and the Ouzo effect in partially miscible
ternary liquid mixtures.
AB - This work investigates the transient equilibration process when partially
miscible ternary liquid mixtures of two different compositions are brought into
contact with each other. Diffusional coupling effects are shown to become
increasingly significant as the mixture compositions approach the meta-stable
regions of the phase equilibrium diagrams. The proper modelling of coupled
diffusion phenomena requires the use of a Fick diffusivity matrix [D], with
inclusion of non-zero off-diagonal elements. The primary objective of this
article is to develop a simple, robust, procedure for the estimation of the
matrix [D], using the Maxwell-Stefan (M-S) formulation as a convenient starting
point. In the developed simplified approach, the Fick diffusivity matrix [D] is
expressed as the product of a scalar diffusivity and the matrix of thermodynamic
correction factors [Gamma]. By detailed examination of experimental data for the
matrix [D] in a wide variety of ternary mixtures, it is deduced that the major
contribution of diffusional coupling arises from the contributions of non-ideal
solution thermodynamics, quantified by the matrix of thermodynamic correction
factors [Gamma]. An important consequence of strong thermodynamic coupling is
that equilibration trajectories are serpentine in shape and may exhibit
incursions into meta-stable zones opening up the possibility of spontaneous
emulsification and the Ouzo effect. If diffusional coupling effects are ignored,
the equilibration trajectory is linear in composition space. For a wide variety
of partially miscible ternary mixtures, it is demonstrated that the corresponding
linear equilibration trajectories do not anticipate the possibility of
emulsification.
PMID- 26421936
TI - A Study of the Monohydrate and Dihydrate Complexes of Perfluoropropionic Acid
Using Chirped-Pulse Fourier Transform Microwave (CP-FTMW) Spectroscopy.
AB - This work reports the first known spectroscopic observation of the monohydrate
and dihydrate complexes of perfluoropropionic acid (PFPA). The spectra have been
observed using a chirped-pulse Fourier transform microwave (CP-FTMW) spectrometer
in the 7750 to 14,250 MHz region. The structures of the species have been
confirmed with the aid of ab initio quantum chemical calculations. Rotational
constants A, B, and C have been determined and reported for both species along
with centrifugal distortion constants DeltaJ, DeltaJK, DeltaK, deltaJ, deltaK for
H2O-PFPA and DeltaJ, DeltaJK, and deltaJ for (H2O)2-PFPA. Effects due to large
amplitude motions were not observable in these experiments. Structures of the
complexes have been determined using a combination of experimental second moment
values and ab initio results. The complexation of the -OH of one or two water
molecules has been found to occur in the plane of the carboxylic acid group
forming a six- or eight-member ring.
PMID- 26421937
TI - A rapid and efficient one-pot method for the reduction of N-protected alpha-amino
acids to chiral alpha-amino aldehydes using CDI/DIBAL-H.
AB - N-Protected amino acids can be easily converted into chiral alpha-amino aldehydes
in a one-pot reaction by activation with CDI followed by reduction with DIBAL-H.
This method delivers Boc-, Cbz- and Fmoc-protected amino aldehydes from
proteinogenic amino acids in very good isolated yields and complete
stereointegrity.
PMID- 26421938
TI - In Situ ATR FTIR Spectroscopic Study of the Formation and Hydration of a
Fucoidan/Chitosan Polyelectrolyte Multilayer.
AB - The formation of fucoidan/chitosan-based polyelectrolyte multilayers (PEMs) has
been studied with in situ Fourier transform infrared (FTIR) spectroscopy.
Attenuated total reflectance (ATR) FTIR spectroscopy has been used to follow the
sequential build-up of the multilayer, with peaks characteristic of each polymer
being seen to increase in intensity with each respective adsorption stage. In
addition, spectral processing has allowed for the extraction of spectra from
individual adsorbed layers, which have been used to provide unambiguous
determination of the adsorbed mass of the PEM at each stage of formation. The PEM
was seen to undergo a transition in growth regimes during build-up: from supra
linear to linear. In addition, the wettability of the PEM has been probed at each
stage of the build-up, using the captive bubble contact angle technique. The
contact angles were uniformly low, but showed variation in value depending on the
nature of the outer polymer layer, and this variation correlated with the overall
percentage hydration of the PEM (determined from FTIR and quartz crystal
microbalance data). The nature of the hydration water within the polyelectrolyte
multilayer has also been studied with FTIR spectroscopy, specifically in situ
synchrotron ATR FTIR microscopy of the multilayer confined between two solid
surfaces. The acquired spectra have enabled the hydrogen bonding environment of
the PEM hydration water to be determined. The PEM hydration water is seen to have
an environment in which it is subject to fewer hydrogen bonding interactions than
in bulk electrolyte solution.
PMID- 26421939
TI - Poly(ionic liquid)s as phase splitting promoters in aqueous biphasic systems.
AB - Aqueous biphasic systems (ABSs) provide a sustainable and efficient alternative
to conventional liquid-liquid extraction techniques with volatile organic
solvents, and can be used for the extraction, recovery, and purification of
diverse solutes. In this work, and for the first time, ABSs composed of
poly(ionic liquid)s (PILs) and inorganic salts were measured at 25 degrees C and
atmospheric pressure. New PILs having pyrrolidinium polycations combined with
different counter-anions, namely acetate [Ac](-), trifluoroacetate [TFAc](-),
hexanoate [Hex](-), adipate [Adi](-), and citrate [Cit](-) were synthesized, by a
simple and environmentally-friendly procedure, and characterized. The effect of
the PIL features, namely molecular weight and anionic character, and other
experimental variables, such as temperature, on the phase splitting ability was
researched. The aptitude of the studied ABS to be implemented as separation
technologies was also evaluated through the use of a model biomolecule,
tryptophan.
PMID- 26421940
TI - Pediatric Venous Thromboembolism--Like Adult Clots, Only Smaller.
PMID- 26421942
TI - Balanced Ambipolar Poly(diketopyrrolopyrrole-alt-tetrafluorobenzene)
Semiconducting Polymers Synthesized via Direct Arylation Polymerization.
AB - The synthesis of an ambipolar pi-conjugated copolymer consisting of alternating
diketopyrrolopyrrole and tetrafluorobenzene via direct arylation polymerization
(DAP) is reported. Two different combinations of monomers are investigated under
various catalytic conditions for DAP. The target polymer obtained under an
optimized catalytic condition shows minimal structural defects, a number-average
molecular weight of 33.2 kDa, and balanced electron and hole mobility of 1 * 10(
2) cm(2) V(-1) S(-1) in the organic field-effect transistors fabricated and
tested under ambient conditions.
PMID- 26421941
TI - Known-component 3D-2D registration for quality assurance of spine surgery pedicle
screw placement.
AB - A 3D-2D image registration method is presented that exploits knowledge of
interventional devices (e.g. K-wires or spine screws-referred to as 'known
components') to extend the functionality of intraoperative
radiography/fluoroscopy by providing quantitative measurement and quality
assurance (QA) of the surgical product. The known-component registration (KC-Reg)
algorithm uses robust 3D-2D registration combined with 3D component models of
surgical devices known to be present in intraoperative 2D radiographs. Component
models were investigated that vary in fidelity from simple parametric models
(e.g. approximation of a screw as a simple cylinder, referred to as
'parametrically-known' component [pKC] registration) to precise models based on
device-specific CAD drawings (referred to as 'exactly-known' component [eKC]
registration). 3D-2D registration from three intraoperative radiographs was
solved using the covariance matrix adaptation evolution strategy (CMA-ES) to
maximize image-gradient similarity, relating device placement relative to 3D
preoperative CT of the patient. Spine phantom and cadaver studies were conducted
to evaluate registration accuracy and demonstrate QA of the surgical product by
verification of the type of devices delivered and conformance within the
'acceptance window' of the spinal pedicle. Pedicle screws were successfully
registered to radiographs acquired from a mobile C-arm, providing TRE 1-4 mm and
<5 degrees using simple parametric (pKC) models, further improved to <1 mm and
<1 degrees using eKC registration. Using advanced pKC models, screws that did
not match the device models specified in the surgical plan were detected with an
accuracy of >99%. Visualization of registered devices relative to surgical
planning and the pedicle acceptance window provided potentially valuable QA of
the surgical product and reliable detection of pedicle screw breach. 3D-2D
registration combined with 3D models of known surgical devices offers a novel
method for intraoperative QA. The method provides a near-real-time independent
check against pedicle breach, facilitating revision within the same procedure if
necessary and providing more rigorous verification of the surgical product.
PMID- 26421943
TI - Design Strategies for CeO2-MoO3 Catalysts for DeNOx and Hg(0) Oxidation in the
Presence of HCl: The Significance of the Surface Acid-Base Properties.
AB - A series of CeMoOx catalysts with different surface Ce/Mo ratios was synthesized
by a coprecipitation method via changing precipitation pH value. The surface
basicity on selective catalytic reduction (SCR) catalysts (CeMoOx and VMo/Ti) was
characterized and correlated to the durability and activity of catalyst for
simultaneous elimination of NOx and Hg(0). The pH value in the preparation
process affected the surface concentrations of Ce and Mo, the Brunauer-Emmett
Teller (BET) specific surface area, and the acid-base properties over the CeMoOx
catalysts. The O 1s X-ray photoelectron spectroscopy (XPS) spectra and CO2
temperature programmed desorption (TPD) suggested that the surface basicity
increased as the pH value increased. The existence of strong basic sites
contributed to the deactivation effect of HCl over the VMo/Ti and CeMoOx
catalysts prepared at pH = 12. For the CeMoOx catalysts prepared at pH = 9 and 6,
the appearance of surface molybdena species replaced the surface -OH, and the
existence of appropriate medium-strength basic sites contributed to their
resistance to HCl poisoning in the SCR reaction. Moreover, these sites
facilitated the adsorption and activation of HCl and enhanced Hg(0) oxidation. On
the other hand, the inhibitory effect of NH3 on Hg(0) oxidation was correlated
with the competitive adsorption of NH3 and Hg(0) on acidic surface sites.
Therefore, acidic surface sites may play an important role in Hg(0) adsorption.
The characterization and balance of basicity and acidity of an SCR catalyst is
believed to be helpful in preventing deactivation by acid gas in the SCR reaction
and simultaneous Hg(0) oxidation.
PMID- 26421944
TI - Health impacts due to particulate air pollution in Volos City, Greece.
AB - There is great consensus among the scientific community that suspended
particulate matter is considered as one of the most harmful pollutants,
particularly the inhalable particulate matter with aerodynamic diameter less than
10 MUm (PM10) causing respiratory health problems and heart disorders. Average
daily concentrations exceeding established standard values appear, among other
cases, to be the main cause of such episodes, especially during Saharan dust
episodes, a natural phenomenon that degrades air quality in the urban area of
Volos. In this study the AirQ2.2.3 model, developed by the World Health
Organization (WHO) European Center for Environment and Health, was used to
evaluate adverse health effects by PM10 pollution in the city of Volos during a 5
year period (2007-2011). Volos is a coastal medium size city in the Thessaly
region. The city is located on the northern side of the Gulf of Pagassitikos, on
the east coast of Central Greece. Air pollution data were obtained by a fully
automated monitoring station, which was established by the Municipal Water Supply
and Sewage Department in the Greater Area of Volos, located in the centre of the
city. The results of the current study indicate that when the mean annual PM10
concentration exceeds the corresponding European Union (EU) threshold value, the
number of hospital admissions for respiratory disease (HARD) is increased by 25%
on average. There is also an estimated increase of about 2.5% in HARD compared to
the expected annual HARD cases for Volos. Finally, a strong correlation was found
between the number of days exceeding the EU daily threshold concentration ([PM10]
>= 50 MUg m(-3)) and the annual HARD cases.
PMID- 26421945
TI - Optimizing 1-MUs-Resolution Single-Molecule Force Spectroscopy on a Commercial
Atomic Force Microscope.
AB - Atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) is
widely used to mechanically measure the folding and unfolding of proteins.
However, the temporal resolution of a standard commercial cantilever is 50-1000
MUs, masking rapid transitions and short-lived intermediates. Recently, SMFS with
0.7-MUs temporal resolution was achieved using an ultrashort (L = 9 MUm)
cantilever on a custom-built, high-speed AFM. By micromachining such cantilevers
with a focused ion beam, we optimized them for SMFS rather than tapping-mode
imaging. To enhance usability and throughput, we detected the modified
cantilevers on a commercial AFM retrofitted with a detection laser system
featuring a 3-MUm circular spot size. Moreover, individual cantilevers were
reused over multiple days. The improved capabilities of the modified cantilevers
for SMFS were showcased by unfolding a polyprotein, a popular biophysical assay.
Specifically, these cantilevers maintained a 1-MUs response time while
eliminating cantilever ringing (Q ? 0.5). We therefore expect such cantilevers,
along with the instrumentational improvements to detect them on a commercial AFM,
to accelerate high-precision AFM-based SMFS studies.
PMID- 26421946
TI - A comparison of the effectiveness of an adult nutrition education program for
Aboriginal and non-Aboriginal Australians.
AB - BACKGROUND: Adult nutrition education is an important component of broader
societal efforts to address the high prevalence of nutrition-related diseases. In
Australia, Aboriginal people are a critical target group for such programs
because of their substantially higher rates of these diseases. OBJECTIVE: The aim
of this study was to assess the relative effectiveness of an adult nutrition
education program for Aboriginal and non-Aboriginal participants. METHODS: Pre
and post-course evaluation data were used to assess changes in confidence in
ability to buy healthy foods on a budget, nutrition knowledge, and dietary
behaviours among individuals attending FOODcents nutrition education courses. The
total sample of 875 Western Australians included 169 who self-identified as
Aboriginal or Torres Strait Islander. RESULTS: Perceptions of course usefulness
were very high and comparable between Aboriginal and non-Aboriginal participants.
Significantly larger improvements in confidence, nutrition knowledge, and
reported consumption behaviours were evident among Aboriginal participants.
CONCLUSION: The findings suggest that adult nutrition education programs that
address specific knowledge and skill deficits that are common among disadvantaged
groups can be effective for multiple target groups, and may also assist in
reducing nutrition-related inequalities.
PMID- 26421947
TI - Happiness and longevity in the United States.
AB - This is the first study to our knowledge to examine the relationship between
happiness and longevity among a nationally representative sample of adults. We
use the recently-released General Social Survey-National Death Index dataset and
Cox proportional hazards models to reveal that overall happiness is related to
longer lives among U.S. adults. Indeed, compared to very happy people, the risk
of death over the follow-up period is 6% (95% CI 1.01-1.11) higher among
individuals who are pretty happy and 14% (95% CI 1.06-1.22) higher among those
who are not happy, net of marital status, socioeconomic status, census division,
and religious attendance. This study provides support for happiness as a stand
alone indicator of well-being that should be used more widely in social science
and health research.
PMID- 26421948
TI - Trauma and Chinese heroin users.
AB - This qualitative study explores the traumas of Chinese heroin users. The results
showed that the Chinese experience traumas during (childhood, later in life but
prior to heroin-use onset, and throughout their heroin-use career. Themes related
to the traumas include the historical economic transition, the value of family
orientation, an emphasis on scholarly pursuits, the shame orientation, and a
scarcity of resources conducive to recovery. This article provides a framework to
understand the traumas experienced by Chinese people and offers insights on how
macrofactors may impact the trauma and its treatment in different societies.
PMID- 26421949
TI - Photo Lewis acid generators: photorelease of B(C6F5)3 and applications to
catalysis.
AB - A series of molecules capable of releasing of the strong organometallic Lewis
acid B(C6F5)3 upon exposure to 254 nm light have been developed. These photo
Lewis acid generators (PhLAGs) can now serve as photoinitiators for several
important B(C6F5)3-catalyzed reactions. Herein is described the synthesis of the
triphenylsulfonium and diphenyliodonium salts of carbamato- and hydridoborates,
their establishment as PhLAGs, and studies aimed at defining the mechanism of
borane release. Factors affecting these photolytic reactions and the application
of this concept to photoinduced hydrosilylation reactions and construction of
siloxane scaffolds are also discussed.
PMID- 26421950
TI - [Tubulointerstitial rejection of renal allografts].
AB - Tubulo-intersticial rejection represents T-cell mediated rejection of kidney
allografts with the morphology of immune-mediated interstitial nephritis.
Diagnosis is dependent on the histopathological evaluation of a graft biopsy
sample. The key morphological features are interstitial inflammatory infiltrate
and damage to tubular epithelial cell which in severe cases can result in the
ruptures of the tubular basement membranes. The differential diagnosis of tubulo
interstitial rejection includes acute interstitial nephritis and viral
inflammatory kidney diseases, mainly polyomavirus nephropathy.
PMID- 26421952
TI - [Infections after kidney transplantation].
AB - Immunosuppressed kidney transplant recipients are at risk for a variety of
infectious complications and more than half of them suffered from this
complication in the early post-transplant period. Despite the fact that the long
term risk of serious infectious complications in the early postoperative period
decreased, remain the infection the most frequent cause of morbidity in the first
6 months after transplant. It is important to realize that the clinical
manifestations of infection in the compromised host are variable and often
atypical. In the later period, infections that affect the kidney graft become
clinically important, and some of them occur only in immunosuppressed patients.
Here we will discuss polyomavirus nephropathy which represents the most important
and most frequent viral disease of renal allografts.
PMID- 26421951
TI - [Antibody-mediated rejection of renal allograft and the update Banff
classification 2013].
AB - The view on the role of donor-specific antibodies in organ transplantation has
been changed during the last several decades. Today, it is considered that the
majority of cases of the late renal allograft dysfunction and loss are caused by
the presence of donor-specific antibodies to HLA antigens. The real breakthrough
in the diagnosis of antibody-mediated rejection was represented by the discovery
of C4d, which enabled the determination of the diagnostic criteria of acute and
later chronic antibody-mediated rejection. Although detection of C4d has been the
cornerstone in the diagnosis of antibody-mediated rejection for over 10 years, it
has become clear that some cases with similar morphological and clinical features
do not have detectable C4d. Outcomes of key studies concerning presence of donor
specific antibodies and morphological features in the graft biopsy samples
resulted in the modification of Banff classification of 2013, which includes
integrating C4d negative antibody-mediated rejection and also that acute vascular
rejection (v1, v2) can be a part of the antibody-mediated rejection.
PMID- 26421953
TI - Shadow cell differentiation in endometrioid carcinomas of the uterus. Its
frequent occurrence and beta-catenin expression.
AB - Shadow cell differentiation (SCD) is typical for pilomatrixoma and related
follicular tumors of the skin. However, it has been described rarely in some
extra-cutaneous lesions such as gonadal teratoma, craniopharyngioma, odontogenic
cyst, and in rare visceral carcinomas (lung, bladder, gallbladder, uterus, ovary,
and colon). In our practice, we have noticed that the occurrence of shadow cells
is not very rare in endometrioid carcinoma (EC) of the uterus. For exact
determination of SCD in these tumors, we reviewed 59 consecutive cases of uterine
EC. The series included curettage and hysteroscopic specimens. We have found SCD
in 9 (15.3 %) of the tumors. In these cases, the age of the patients and FIGO
grade did not differ significantly from other ECs. Immunohistochemically, all ECs
with SCD showed nuclear expression of beta-catenin in areas of SCD, indicating a
possible role of the Wnt signaling pathway in tumorigenesis as well as a role of
nuclear accumulation of beta-catenin by trans-differentiation from glandular
toward squamous and shadow cell phenotypes. We have found that the relatively
frequent presence of SCD in ECs can assists in the diagnosis of these tumors.
PMID- 26421954
TI - [Neuroendocrine tumor of the breast--metastasis or primary breast carcinoma? Case
report].
AB - A 74-year-old women with a history of neuroendocrine tumor in the terminal ileum
presented on screening mammography with an irregular hypoechogenic mass in the
upper outer quadrant of the left breast. A core biopsy showed a neuroendocrine
tumor, interpreted as a probable metastasis from the intestinal primary. Other
masses were found in the right lobe of the liver. Resection of the masses in the
breast and liver was performed at the same time. Morphological and
immunohistochemical findings (positive neuroendocrine markers, estrogene
receptors and negative cytokeratine 7, mammaglobin, GCDFP-15, cytokeratine 20 and
progesterone receptors) were consistent with a diagnosis of a metastatic well
differentiated neuroendocrine tumor, despite some estrogen receptor positivity.
Issues of primary and metastatic breast neuroendocrine tumors are discussed in
detail.
PMID- 26421955
TI - [Melanocytic matricoma--a case report].
AB - A rare skin tumor (melanocytic matricoma), 6 mm in diameter, was diagnosed on the
skin of the back in a 66-year-old man. It was composed of two cellular types: 1.
epithelial cells with hair follicle differentiation and 2. dendritic melanocytes.
After two years of follow-up there are no signs of a relapse or generalisation of
the tumor.
PMID- 26421956
TI - Pyloric gland adenoma: a histologic, immunohistochemical and molecular genetic
study of 23 cases.
AB - Pyloric gland adenoma is a rare neoplasm with a gastric epithelial
differentiation. We report 23 cases of pyloric gland adenoma in older persons,
with a mean age of 74 years (range 52 - 87 years). They occurred in the esophagus
(3 cases), corporal gastric mucosa (7 cases), duodenum (10 cases), gallbladder (2
cases), and choledochus (one case). Histologically, they were characterized by
closely packed pyloric gland-type tubules with a monolayer of cuboidal to low
columnar epithelial cells containing basally located round nuclei, and a
superficial layer of tall, columnar, foveolar-type epithelium.
Immunohistochemically, most tumor glands expressed pyloric gland mucin MUC6,
whereas MUC5AC was positive in superficial gastric foveolar epithelium, and in a
minority of glands. In addition, scattered neuroendocrine cells positive for
chromogranin A and/or synaptophysin were seen in all cases. In 3 cases (two cases
in the gallbladder and one case in the esophagus), areas of intestinal metaplasia
with CK20, CDX2, and MUC2 positivity were found. Focal low-grade dysplasia was
found in five cases (21.7%), and diffuse high-grade dysplasia was seen in one
adenoma (4.4%), i.e., 6 of 23 PGAs (26.1%) showed dysplastic features. In one
esophageal case, an invasive adenocarcinoma was diagnosed. Scattered p53 positive
cells were found in all cases. Their number was higher in lesions with low-grade
dysplasia and it was substantially increased in adenoma with high-grade dysplasia
and in adenocarcinoma. Our molecular genetic results indicate that pyloric gland
adenomas neoplastic nature is associated with p53 accumulation, mutations in
oncogenes GNAS, KRAS, CTTNB1 and tumor suppressor genes SMAD4, and TP53. Pyloric
gland adenoma can evolve into dysplasia and adenocarcinoma.
PMID- 26421957
TI - A two-centre, open-label, randomised study of ovulation inhibition with three
transdermal contraceptive patches, each containing different amounts of ethinyl
estradiol and gestodene in healthy, young women.
AB - Here we report the findings of a two-centre, open-label, randomised, Phase IIa
study designed to investigate whether an ethinyl estradiol (EE)/gestodene (GSD)
patch that has been developed (referred to herein as the 'EE/GSD patch') reliably
inhibits ovulation in comparison with patches delivering lower doses of these
hormones. The study rationale was to provide justification of the doses of EE and
GSD selected for the EE/GSD patch. Healthy women, aged 18-35 years, were
randomised to receive treatment with either the EE/GSD patch, a 'reduced-GSD
patch' (delivering similar amounts of EE and approximately half the amount of
GSD) or a 'reduced-EE/GSD patch' (delivering half the amount of EE and GSD).
Treatment was administered for three 28-day cycles (three * 7 patch-wearing days,
plus a 7-day patch-free interval). The primary pharmacodynamic variable was the
percentage of women with ovulation in at least one of Cycles 2 and/or 3, as
indicated by Hoogland score. Pharmacokinetic parameters for EE and GSD were also
measured. Results indicated that the EE/GSD patch effectively suppressed
ovulation, while patches delivering lower doses of EE and GSD were less effective
for this purpose. All three patches showed comparable tolerability.
PMID- 26421958
TI - A preliminary investigation into the psychometric properties of the Dublin
Extrapersonal Neglect Assessment (DENA): A novel screening tool for extrapersonal
neglect.
AB - Extrapersonal neglect is one clinical manifestation that can occur following
stroke. Existing neglect assessment procedures have been criticised for lengthy
administration and do not assess how extrapersonal space is affected. This study
investigated the psychometric properties of a new, time-efficient screening tool
for extrapersonal neglect. Full ethical approval was granted and consent obtained
from 50 participants with first-time stroke. Participants were screened for
extrapersonal neglect on two consecutive days by two raters using the Dublin
Extrapersonal Neglect Assessment (DENA) to test inter-rater reliability.
Construct validity of the DENA was investigated by comparing the DENA to the
Catherine Bergego Scale (CBS). Additional analyses were calculated between the
DENA and the extrapersonal items of the CBS (CBS-E). The kappa statistic,
intraclass correlation coefficients (ICCs) and Bland Altman analyses were
calculated to determine excellent inter-rater reliability (ICC 0.971, kappa =
.876) and significant correlation between the DENA and the CBS and CBS-E (ICC
0.870, 0.934, kappa = .793, .833, respectively). Bland Altman analyses
demonstrated acceptable levels of agreement between the DENA raters, and the DENA
and CBS, with no systematic differences evident. The DENA provides clinicians
with a quick and psychometrically sound screening tool for extrapersonal neglect
to ensure this impairment is addressed in stroke rehabilitation.
PMID- 26421959
TI - Mast cells phagocyte Candida albicans and produce nitric oxide by mechanisms
involving TLR2 and Dectin-1.
AB - Candida albicans (C. albicans) is a fungus commonly found in the human mucosa,
which may cause superficial and systemic infections, especially in
immunosuppression. Until now, the main actors in the defense against this fungus
are the epithelial cells, neutrophils, macrophages/monocytes and dendritic cells.
However, mast cells are strategically located to play a first line of anti
Candida defense and it has appropriate mechanisms to do it. As with other cells,
the recognition of C. albicans occurs meanly via TLR2 and Dectin-1. We assess the
TLR2/Dectin-1 involvement in phagocytosis and production of nitric oxide (NO) and
reactive oxygen species (ROS) by mast cells challenged with C. albicans. Bone
marrow-derived mast cells (MC) from wild type (Wt) or knockout (TLR2-/-) mice
C57BL/6 were subjected to in vitro Dectin-1 blockade. After challenged with FITC
labeled C. albicans or zymosan, phagocytosis was analyzed by microscopy. The
intracellular production of NO and ROS was measured by DAF-FM diacetate and
CellROX Deep/Red Reagent kits. The nitrite formation and hydrogen peroxide
release were analyzed by Griess reaction and Amplex Red Hydrogen
Peroxide/Peroxidase Assay Kit. Wt/MC phagocytose C. albicans with production of
intracellular NO, but not ROS. Moreover, increased levels of nitrite were also
observed. The absence and/or blockade of TLR2/Dectin-1 caused significant
decreased in C. albicans phagocytosis and NO production. Our results showed that
mast cells are able to phagocytose and produce NO against C. albicans via
TLR2/Dectin-1. Therefore, mast cells could be important during the course of
Candida infection and as a therapeutic target.
PMID- 26421961
TI - Simultaneous Phase Transfer and Surface Modification of TiO2 Nanoparticles Using
Alkylphosphonic Acids: Optimization and Structure of the Organosols.
AB - An original protocol of simultaneous surface modification and transfer from
aqueous to organic phases of anatase TiO2 nanoparticles (NPs) using
alkylphosphonic acids (PAs) is studied. The influence of the solvent, the nature
and concentration of the PA, and the size, concentration, and aggregation state
of the TiO2 NPs was investigated. Complete transfer was observed for linear alkyl
chains (5, 8, 12, and 18 C atoms), even at very high sol concentrations. After
transfer, the grafted NPs were characterized by (31)P solid-state MAS NMR. The
dispersion state of NPs before and after phase transfer was monitored by dynamic
light scattering (DLS). Small-angle neutron scattering (SANS) was used to
characterize the structure of PA-grafted NPs in the organic solvent. Using a
quantitative core-shell model cross-checked under different contrast conditions,
it is found that the primary particles making up the NPs are homogeneously
grafted with a solvated PA-layer. The nanometric thickness of the latter is shown
to increase with the length of the linear carbon chain of the PA, independent of
the size of the primary TiO2 NP. Interestingly, a reversible temperature
dependent aggregation was evidenced visually for C18PA, and confirmed by DLS and
SANS: heating the sample induces the breakup of aggregates, which reassemble upon
cooling. Finally, in the case of NPs agglomerated by playing with the pH or the
salt concentration of the sols, the phase transfer with PA is capable of
redispersing the agglomerates. This new and highly versatile method of NP surface
modification with PAs and simultaneous transfer is thus well suited for obtaining
well-dispersed grafted NPs.
PMID- 26421960
TI - Expression of surfactant proteins SP-A and SP-D in murine decidua and
immunomodulatory effects on decidual macrophages.
AB - Surfactant proteins SP-A and SP-D are pattern recognition innate immune molecules
that belong to the C-type lectin family. In lungs, they play an important role in
the clearance of pathogens and control of inflammation. SP-A and SP-D are also
expressed in the female reproductive tract where they play an important role in
pregnancy and parturition. However, the role of SP-A and SP-D expressed at the
feto-maternal interface (decidua) remains unclear. Here, we have examined the
expression of SP-A and SP-D in the murine decidua at 17.5 (pre-parturition) and
19.5dpc (near parturition) and their effect on lipopolysaccharide (LPS)-treated
decidual macrophages. SP-A and SP-D were localized to stromal cells in the murine
decidua at 17.5 and 19.5dpc in addition to cells lining the maternal spiral
artery. Purified pre-parturition decidual cells were challenged with LPS with and
without SP-A or SP-D, and expression of F4/80 and TNF-alpha were measured by flow
cytometry. On their own, SP-A or SP-D did not affect the percentage of F4/80
positive cells while they suppressed the percentage of TNF-alpha positive cells.
However, simultaneous addition of SP-A or SP-D, together with LPS, reduced TNF
alpha secreting F4/80 positive cells. It is likely that exogenous administration
of SP-A and SP-D in decidua can potentially control infection and inflammation
mediators during spontaneous term labor and infection-induced preterm labor.
Thus, the presence of SP-A and SP-D in the murine decidua is likely to play a
protective role against intrauterine infection during pregnancy.
PMID- 26421962
TI - Quantification of 4'-geranyloxyferulic acid (GOFA) in honey samples of different
origin by validated RP-HPLC-UV method.
AB - Natural honey has been employed as a nutraceutical agent with benefits and
therapeutic promises for humans for many centuries. It has been largely used as
food and medicine by all generations, traditions, and civilizations, both ancient
and modern. Several chemicals having beneficial effects for human health have
been reported as components of natural honey and these include sugars, organic
acids, aminoacids, minerals, and vitamins. Also some important phytochemicals
have been described and these comprise tannins, flavonoids, terpenes, saponins,
and alkaloids. In this note it is described the successful application of a RP
HPLC-UV-vis method for the separation and quantification of 4'-geranyloxyferulic
acid (GOFA) in four honey samples of different origin. Concentration values
showed a great variation between the four samples tested, being chestnut honey
the one richest in GOFA (7.87 mg/g). The findings described herein represent the
first example reported in the literature of the characterization of an
oxyprenylated phenylpropanoid in honey.
PMID- 26421963
TI - PARACENTRAL ACUTE MIDDLE MACULOPATHY IN BIRDSHOT CHORIORETINOPATHY: A NOVEL
ASSOCIATION.
AB - BACKGROUND/PURPOSE: To present a novel case of paracentral acute middle
maculopathy in association with birdshot chorioretinopathy. METHODS: Case report.
RESULTS: A patient presented with decreased vision and findings of uveitis,
vasculitis and a paracentral scotoma. Multimodal imaging was consistent with
paracentral acute middle maculopathy in the setting of a multifocal
chorioretinopathy and a laboratory workup was consistent with birdshot
chorioretinopathy. CONCLUSION: Paracentral acute middle maculopathy is a newly
described entity that may be associated with birdshot chorioretinopathy, and
clinicians should be aware of it when patients present with new paracentral
scotoma and signs of intraocular inflammation.
PMID- 26421964
TI - SPONTANEOUS RESOLUTION OF MACULAR EPIRETINAL MEMBRANES AFTER FLUORESCEIN
POTENTIATED ARGON LASER TREATMENT OF VON HIPPEL-LINDAU ASSOCIATED RETINAL
HEMANGIOMAS: CASE REPORT AND REVIEW OF LITERATURE.
AB - PURPOSE: To illustrate spontaneous resolution of macular epiretinal membranes and
inactivation of retinal hemangioma exudation after fluorescein potentiated argon
laser treatment of bilateral capillary hemangiomas in a patient with a de novo
heterozygous deletion in Exon 2 of the von Hippel-Lindau gene. METHODS:
Interventional case report. RESULTS: A 23-year-old man with subjective complaints
of blurry vision, photophobia, and glare. On presentation, visual acuity was
20/20 in the right eye and 20/25 in the left eye with metamorphopsia. On the
basis of bilateral retinal hemangiomas on clinical examination and
characterization with multimodal imaging, a diagnosis of von Hippel-Lindau
disease was made. Genetic testing identified a de novo, disease-causing
heterozygous deletion in Exon 2 of the von Hippel-Lindau gene. The patient
underwent 4 sessions of fluorescein potentiated 532 nm argon green laser
treatment directed at retinal hemangiomas. No adverse sequelae of laser treatment
were noted. Seven months after the initial presentation, the patient's vision was
20/20 in both eyes with interval resolution of metamorphopsia. There was
spontaneous resolution of a macular epiretinal membrane with normalization of the
macular retinal microstructure. The retinal hemangiomas in both eyes appeared
inactive, and no new lesions were noted. CONCLUSION: Fluorescein potentiated
argon laser successfully treated bilateral retinal hemangiomas in our patient
with von Hippel-Lindau disease. Additional studies to characterize the full
clinical potential of fluorescein potentiated argon laser therapy may be
warranted.
PMID- 26421965
TI - Resolution of fibrinogen deficiency in a patient with congenital afibrinogenemia
after liver transplantation.
PMID- 26421969
TI - Are There Differences in Central Coherence and Set Shifting Across the Subtypes
of Anorexia Nervosa?: A Systematic Review.
AB - Anorexia nervosa (AN) has been associated with weaknesses in central coherence
and set shifting. In this line, it has been proposed to directly address these
neuropsychological features in treatment (e.g., cognitive remediation therapy).
It is not clear, however, whether the 2 subtypes of AN, the restricting (AN-R)
and bingeing/purging (AN-BP) type, have the same amount of problems in these
domains. A systematic search of the literature was conducted, using the databases
Web of Science and PubMed, looking for studies on the comparison of AN-R and AN
BP in performing central coherence/set-shifting tasks. Notably, very few authors
describe the results of a direct comparison of the performance of patients with
AN-R and AN-BP. In summary, the available indications for possible group
differences are not strong enough to draw definitive conclusions.
PMID- 26421970
TI - Sex Bias in Classifying Borderline and Narcissistic Personality Disorder.
AB - This study investigated sex bias in the classification of borderline and
narcissistic personality disorders. A sample of psychologists in training for a
post-master degree (N = 180) read brief case histories (male or female version)
and made DSM classification. To differentiate sex bias due to sex stereotyping or
to base rate variation, we used different case histories, respectively: (1) non
ambiguous case histories with enough criteria of either borderline or
narcissistic personality disorder to meet the threshold for classification, and
(2) an ambiguous case with subthreshold features of both borderline and
narcissistic personality disorder. Results showed significant differences due to
sex of the patient in the ambiguous condition. Thus, when the diagnosis is not
straightforward, as in the case of mixed subthreshold features, sex bias is
present and is influenced by base-rate variation. These findings emphasize the
need for caution in classifying personality disorders, especially borderline or
narcissistic traits.
PMID- 26421971
TI - The Need for Vigilance in the Marketing of Genomic Tests in Psychiatry.
PMID- 26421972
TI - The efficacy of sugar labeling formats: Implications for labeling policy.
AB - OBJECTIVE: To examine knowledge of sugar recommendations and test the efficacy of
formats for labeling total and added sugar on pre-packaged foods. METHODS: Online
surveys were conducted among 2008 Canadians aged 16-24. Participants were asked
to identify recommended limits for total and added sugar consumption. In
Experiment 1, participants were randomized to one of six labeling conditions with
varying information for total sugar for a high- or low-sugar product and were
asked to identify the relative amount of total sugar in the product. In
Experiment 2, participants were randomized to one of three labels with different
added sugar formats and were asked if the product contained added sugar and the
relative amount of added sugar. RESULTS: Few young people correctly identified
recommendations for total sugar (5%) or added sugar (7%). In Experiment 1, those
who were shown percent daily value information were more likely to correctly
identify the relative amount of total sugar (P < 0.05). In Experiment 2, those
shown added sugar information were more likely to correctly identify that the
product contained added sugar and the relative amount of added sugar in the
product (P < 0.05). CONCLUSIONS: Improved labeling may improve consumer
understanding of the amount of sugars in food products.
PMID- 26421974
TI - Speech processing in children with cochlear implant.
AB - Cochlear implants (CIs) can be used effectively in the profoundly impaired
children individuals. OBJECTIVES: This work was designed to assess speech
processing at brainstem and cortical level in children fitted with CIs to
investigate the possible influence of brainstem processing of speech on the
cortical processing in those children. METHOD: Twenty children fitted with CIs
underwent aided sound-field audiologic evaluation, speech evoked cortical
auditory evoked potentials (S-CAEPs) and according to the results, children were
classified into two groups: group I with good cortical response and group II with
poor cortical response. This was followed by speech evoked ABR (S-ABR) recoding.
RESULTS: P1 component of CAEPs was recorded in all children while other component
showed variable results. S-ABR was recorded in all children even those with poor
S-CAEPs response who showed delayed D, E, F and O latencies. However, S-ABR
amplitudes did not show any significant difference between both groups.
CONCLUSIONS: Children fitted with CI showed immediate cortical activation
following device programming and this activity depends on the age of implantation
as well as the child's age. S-ABR provides a new clinical tool that showed an
important role of brainstem in complex sound processing that contribute to
cortical processing.
PMID- 26421973
TI - Concept-elicitation phase for the development of the pediatric patient-reported
outcome version of the Common Terminology Criteria for Adverse Events.
AB - BACKGROUND: Symptoms arising from disease or treatment are subjective
experiences. Insight into pediatric oncology treatment side effects or symptoms
is ideally obtained from direct inquiry to the ill child. A concept-elicitation
phase in a patient-reported outcome (PRO) instrument design provides an
opportunity to elicit children's voices to shape cancer symptom selection and
terminology. METHODS: Through semistructured, one-on-one, voice-recorded
interviews, symptom data were collected from 96 children with cancer between the
ages of 7 and 20 years who were undergoing oncologic treatment at 7 pediatric
oncology sites in the United States and Canada. RESULTS: The mean number of
symptoms reported per child over the prior 7 days was 1.49 (range, 0-7; median,
1; standard deviation, 1.56). The most common symptoms across all age groups were
tiredness or fatigue, nausea or vomiting, aches or pains, and weakness. There was
not a statistically significant correlation between self-reported wellness and
the number of reported symptoms (r = -0.156, n = 65, P = .215) or the number of
symptoms reported by age group or diagnosis type. Forty participants reported
experiencing a change in their body in the past week, with one-third of these
changes unanticipated. Only through direct questions about feelings were
emotional symptoms revealed because 90.6% of interviewees who discussed feelings
(48 of 53) did so only in the context of direct questioning on feelings.
Adolescents were more likely than younger children to discuss feelings as part of
the interview. CONCLUSIONS: Concept elicitation from children and adolescents has
the potential to enable researchers to develop age-appropriate, accurately
representative PRO measures.
PMID- 26421975
TI - Polarization-Mediated Thermal Stability of Metal/Oxide Heterointerface.
AB - A polarization-mediated heterointerface is designed to research the thermal
stability of magnetic metal/oxide interfaces. Using polarization engineering, the
thermal stability of the interface between BiFeO3 and CoFeB can be improved by
about 100 degrees C. This finding provides new insight into the chemistry of the
metal/oxide heterointerface.
PMID- 26421977
TI - Ossicular calisthenics: Pneumomassage of the tympanic membrane.
AB - OBJECTIVES/HYPOTHESIS: Throughout the latter portion of the 19th and early 20th
centuries, pneumomassage devices were widely used by otologists to treat a
variety of ear diseases. The so-called eardrum massagers produced a regular,
repetitive, oscillatory movement through modifying the air pressure in the ear
canal. The goal of this study was to trace the invention, clinical use,
technological diversification, abandonment, and ultimate resurrection of tympanic
pneumomassage. METHOD: Review of the 19th- and early 20th-century medical
journals, texts, and trade catalogs concerning the tympanic pneumomassage.
RESULTS: In 1884, the Belgian otologist Charles Delstanche introduced what he
called a rarefacteur, and 5 years later he introduced the masseur du tympan. This
lead to a frenzied development of imaginative mechanical and electrical
pneumassagers with a goal to exercise the tympanic membrane and ossicles to
overcome contraction and rigidity. Tympanic pneumomassage rose to prominence in
mainstream otology as a treatment for otitis media, chronic deafness, and
tinnitus. After gradually fading out of the otological practice by the 1930s,
pneumomassage was reintroduced in the 1980s after a half century of obscurity,
this time as a novel invention notably for the treatment of Meniere's disease.
CONCLUSION: The golden era of pneumomassage illustrates the ingenuity of
otologists and medical instrument makers in creating a proliferation of clever
devices, as well as how highly touted treatment methods may become widely adopted
by practitioners despite the lack of efficacy. It also noteworthy that historic
therapeutic methods are sometimes reintroduced for purposes not envisioned by
their original makers. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:1180-1186, 2016.
PMID- 26421978
TI - Vascular restoration: Is there a window of opportunity?
AB - The usage of drug eluting stents (DES) has markedly reduced the rates of coronary
revascularization procedures compared with bare metal stents (BMS). However, this
technology still faces challenges in terms of the prevention of late stent
thrombosis, major adverse cardiac events (MACE) progression, and the catch-up
phenomenon of restenosis. Restoration of endothelial function upon after
stenting, therefore, is the key to mitigating the risk of these toxicities and
determining the level of the efficacy and safety of an implant. Review of the
clinical studies of multiple DES, has suggested that there exists a window of
opportunity, within the first two to three months after stent implantation, for
restoring vascular function. If re-endothelialization reaches sufficient level
within this period, vascular restoration can occur; however, if this opportunity
is missed, re-endothelialization is unlikely to reach the level of endothelial
maturation necessary to prevent the late stent thrombosis, MACE progression and
the catch-up on restenosis. This hypothesis could aid in explaining variable
clinical responses for revascularization treatments such as plain old balloon
angioplasty (POBA), BMS, or DES. Patients could be grouped according to responses
to the different treatment modalities: for Type 1 patients, POBA is sufficient
and safe because they possess the capacity with effective endothelial response;
for Type 2 patients, re-endothelialization occurs within the window but BMS are
needed to maintain the arterial lumen open; for Type 3 individuals, overly
accelerated vascular smooth muscle proliferation render sufficient re
endothelialization impossible. Designing based on this principle predicts that
the next technology advancement for the interventional cardiology will not be
biodegradable DES by default, but rather a DES that can spur early restoration of
the endothelial function within the window period.
PMID- 26421979
TI - Growth hormone signaling pathways.
AB - Over 20years ago, our laboratory showed that growth hormone (GH) signals through
the GH receptor-associated tyrosine kinase JAK2. We showed that GH binding to its
membrane-bound receptor enhances binding of JAK2 to the GHR, activates JAK2, and
stimulates tyrosyl phosphorylation of both JAK2 and GHR. The activated JAK2/GHR
complex recruits a variety of signaling proteins, thereby initiating multiple
signaling pathways and cellular responses. These proteins and pathways include:
1) Stat transcription factors implicated in the expression of multiple genes,
including the gene encoding insulin-like growth factor 1; 2) Shc adapter proteins
that lead to activation of the grb2-SOS-Ras-Raf-MEK-ERK1,2 pathway; 3) insulin
receptor substrate proteins implicated in the phosphatidylinositol-3-kinase and
Akt pathway; 4) signal regulatory protein alpha, a transmembrane scaffold protein
that recruits proteins including the tyrosine phosphatase SHP2; and 5) SH2B1, a
scaffold protein that can activate JAK2 and enhance GH regulation of the actin
cytoskeleton. Our recent work has focused on the function of SH2B1. We have shown
that SH2B1beta is recruited to and phosphorylated by JAK2 in response to GH.
SH2B1 localizes to the plasma membrane, cytoplasm and focal adhesions; it also
cycles through the nucleus. SH2B1 regulates the actin cytoskeleton and promotes
GH-dependent motility of RAW264.7 macrophages. Mutations in SH2B1 have been found
in humans exhibiting severe early-onset childhood obesity and insulin resistance.
These mutations impair SH2B1 enhancement of GH-induced macrophage motility. As
SH2B1 is expressed ubiquitously and is also recruited to a variety of receptor
tyrosine kinases, our results raise the possibility that effects of SH2B1 on the
actin cytoskeleton in various cell types, including neurons, may play a role in
regulating body weight.
PMID- 26421980
TI - Sexual Behavior Among Young Carers in the Context of a Kenyan Empowerment Program
Combining Cash-Transfer, Psychosocial Support, and Entrepreneurship.
AB - This study examined associations between sexual initiation, unprotected sex, and
having multiple sex partners in the past year with participation in a three-year
empowerment program targeting orphan and vulnerable children (OVC). The Kenya
based program combines community-conditioned cash transfer, psychosocial
empowerment, health education, and microenterprise development. Program
participants (n = 1,060) were interviewed in a cross-sectional design. Analyses
used gender-stratified hierarchical logit models to assess program participation
and other potential predictors. Significant predictors of increased female sexual
activity included less program exposure, higher age, younger age at most recent
parental death, fewer years of schooling, higher food consumption, higher
psychological resilience, and lower general self-efficacy. Significant predictors
of increased male sexual activity included more program exposure, higher age,
better food consumption, not having a living father, and literacy. Findings
support a nuanced view of current cash transfer programs, where female sexual
activity may be reduced through improved financial status but male sexual
activity may increase. Targeting of OVC sexual risk behaviors would likely
benefit from being tailored according to associations found in this study. Data
suggest involving fathers in sexual education, targeting women who lost a parent
at a younger age, and providing social support for female OVC may decrease risk
of human immunodeficiency virus (HIV) transmission.
PMID- 26421981
TI - In vitro activity against Mycobacterium tuberculosis of levofloxacin,
moxifloxacin and UB-8902 in combination with clofazimine and pretomanid.
AB - Multidrug resistance has become a problem in the management of tuberculosis, with
an urgent need for research into new drugs as well as the development of
efficacious drug combinations and regimens. The main objective of this study was
to assess and compare the efficacy of three antituberculous combinations
(clofazimine/pretomanid/levofloxacin, clofazimine/pretomanid/moxifloxacin and
clofazimine/pretomanid/UB-8902) against multidrug-resistant (MDR) and drug
susceptible clinical isolates of Mycobacterium tuberculosis using an in vitro
adaptation of the chequerboard assay. A total of 7 MDR and 11 drug-susceptible
clinical isolates were studied. The fractional inhibitory concentration index
(FICI) was interpreted as synergism when the value was <0.75, antagonism when it
was >4 and additive activity between these two values. The FICI of all of the
combinations ranged from 1.2 to 2.3, showing additive activity against all of the
isolates. No differences were found between MDR and drug-susceptible isolates. In
conclusion, the three combinations are effective against M. tuberculosis with
equal effects. Moreover, in vitro testing of drug combinations could be useful to
predict their clinical use.
PMID- 26421982
TI - Plenary presentations and public citations from The American Association for
Thoracic Surgery.
AB - OBJECTIVE: We examined the impact of work presented in the plenary sessions at
the meeting of The American Association for Thoracic Surgery (AATS), by
determining how frequently the published papers corresponding to the session
presentations during the past 20 years, were cited; those that were most cited
were identified. METHODS: We reviewed the AATS meeting programs from the 20-year
period from 1994 to 2014 and identified the corresponding publications in the
Journal of Thoracic and Cardiovascular Surgery (JTCVS) from all abstracts
presented at the plenary sessions. Papers were categorized as cardiac, thoracic,
or congenital. References were evaluated for subsequent citation in the Web of
Science (WoS), and Google Scholar (GS). We determined both the median number of
citations overall, and per year. For comparison, we evaluated numbers of
citations in WoS from current JTCVS papers in issues containing the 3 most-cited
plenary session papers. RESULTS: Among 195 published plenary papers, the median
number of citations in WoS and GS was 49 and 76, respectively. The median total
number of citations in WoS was as follows: 51 for cardiac-category papers (n =
105); 61 for thoracic (n = 55), and 41 for congenital (n = 35). These values were
higher than the median total number of citations for contemporary nonplenary
JTCVS papers: cardiac (22, n = 55; P < .001); thoracic (31.5, n = 8; P = .183);
and congenital (15.5, n = 24; P = .002) papers published in JTCVS. The median
number of citations per year since publication for plenary publications was 5.9
(cardiac), 6 (thoracic), and 3.7 (congenital), respectively. CONCLUSIONS:
Publications corresponding to the plenary sessions of the AATS are highly cited
and include some of the seminal studies in our field in the past 20 years.
PMID- 26421983
TI - Periportal fibrosis without cirrhosis does not affect outcomes after continuous
flow ventricular assist device implantation.
AB - OBJECTIVE: This study investigates the relationship of periportal fibrosis on
postoperative outcomes after ventricular assist device (VAD) implantation.
METHODS: Between July 2005 and August 2014, a total of 233 patients were
implanted with continuous flow VADs. Liver biopsy was performed on 16 patients
with concern for liver disease. Survival was evaluated using the Kaplan-Meier
method. The effect of fibrosis on length of stay (LOS) in the intensive care unit
was modeled using Poisson regression. Adjustments were made for age, profile from
the Interagency Registry for Mechanically Assisted Circulatory Support, biopsy,
and model for end-stage liver disease score. RESULTS: Fourteen of the 16 patients
who underwent biopsy had periportal fibrosis without cirrhosis. One-year survival
for the groups with and without biopsy-proven fibrosis was 93% +/- 7% and 86% +/-
2% (P = .97), respectively. The intensive care unit LOS was not different for
those with (median, 7 days; interquartile range: 3-14 days) versus without
fibrosis (median, 6 days; interquartile range 4-10 days; P = .65). Fibrosis (P =
.42), age (0.95), model for end-stage liver disease excluding internal normalized
ratio-XI score (P = .64), performance of a biopsy (P = .28), and Interagency
Registry for Mechanically Assisted Circulatory Support class (P = .70) were not
associated with intensive care unit LOS. Risk was increased of gastrointestinal
bleeding (14% vs 4%; P = .026) in the first year among patients with fibrosis.
CONCLUSIONS: The presence of periportal fibrosis did not affect survival or
outcomes in patients undergoing VAD implantation. These findings suggest that
carefully selected patients with advanced heart failure and hepatic fibrosis
without cirrhosis may achieve acceptable outcomes with VAD implantation.
PMID- 26421984
TI - Will transcatheter valve-in-valve become the standard for replacing the
degenerative aortic valve bioprosthesis? Hold your horses, the jury is still out.
PMID- 26421985
TI - One-year clinical and angiographic results of hybrid myocardial
revascularization: Still a long way to go.
PMID- 26421986
TI - Discussion.
PMID- 26421987
TI - The Incidence of Postconcussion Syndrome Remains Stable Following Mild Traumatic
Brain Injury in Children.
AB - BACKGROUND: Improving our knowledge about the natural history and persistence of
symptoms following mild traumatic brain injury is a vital step in improving the
provision of health care to children with postconcussion syndrome. The purposes
of this study were to (1) determine the incidence and persistence of symptoms
after mild traumatic brain injury and (2) ascertain whether Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), symptom criteria
for postconcussion syndrome in adults are appropriate for use in children.
METHODS: A tertiary care pediatric emergency department was the setting for this
study. This was a prospective observational follow-up cohort study of children
(ages 2 to 18 years) with mild traumatic brain injury. Data were collected in
person during the acute presentation, and subsequent follow-up was performed by
telephone at 7-10 days and 1, 2, and 3 months postinjury. Postconcussion Symptom
Inventory for parents and children was used. The DSM-IV diagnostic criteria for
postconcussion syndrome were explored using receiver operating characteristic
curve analysis. RESULTS: A total of 467 children (62.5% boys, median age 12.04,
range 2.34-18.0) with mild traumatic brain injury participated. The median time
until symptom resolution was 29.0 days (95% confidence intervals: 26.09-31.91).
Three months after injury, 11.8% of children with mild traumatic brain injury
remained symptomatic. Receiver operating curve characteristic analysis of the
postconcussion syndrome criteria successfully classified symptomatic participants
at three months postinjury; the adolescent receiver operating characteristic
curve was excellent with the area under the curve being 0.928 (P < 0.001,
standard error 0.019). CONCLUSIONS: Consistent with our previous study, 11.8% of
children presenting to the emergency room with a mild traumatic brain injury
remain symptomatic at 3 months postinjury. This is the first study to demonstrate
stable incidence rates of postconcussion syndrome in children and that modified
DSM-IV criteria can be used to successfully classify postconcussion syndrome in
children. Although most children report a decay in symptoms over time, 10% of
children develop symptoms even though they initially had a good outcome. Caution
should be used when using only parent report as a surrogate for childhood
outcomes following a concussion.
PMID- 26421988
TI - Recurrent Stroke-Like Episodes in FBXL4-Associated Early-Onset Mitochondrial
Encephalomyopathy.
PMID- 26421990
TI - Spinal Subdural Hematoma in Nonaccidental Trauma.
PMID- 26421989
TI - Successful Treatment of Electrographic Status Epilepticus of Sleep With Felbamate
in a Patient With SLC9A6 Mutation.
AB - BACKGROUND: Mutations of SLC9A6 may cause an X-linked clinical syndrome first
described by Christianson in 1999 in which affected males exhibited profound
intellectual disability, autism, drug-resistant epilepsy, ophthalmoplegia, mild
craniofacial dysmorphism, microcephaly, and ataxia. METHODS: We describe a child
with an SLC9A6 mutation and an electroencephalographic pattern consistent with
electrographic status epilepticus of sleep. RESULTS: Our patient's electrographic
status epilepticus of sleep resolved after treatment with felbamate. Following
treatment, he remained seizure-free but did not make significant or lasting gains
in language. CONCLUSION: Our report extends the clinical epilepsy phenotype in
children with SLC9A6 mutations to include electrographic status epilepticus of
sleep. In addition, felbamate was an effective treatment for electrographic
status epilepticus of sleep in our patient.
PMID- 26421991
TI - Highly efficient and fast pre-activation cyclization of the long peptide:
Succinimidyl ester-amine reaction revisited.
AB - A new method for the pre-activation cyclization of a long peptide is described.
The approach involves the formation of a pre-activated succinimidyl ester species
in advance of amidation, which completely eliminates the potentially troublesome
amine end-capping side reaction. The cyclization reactions proceed with high
efficiency and fast reaction kinetics for the long peptide with 25 residues. The
exploration and large-scale preparation of synthetic cyclic peptides should
become more accessible and feasible with this approach. This method has a
potential to be further applied for the synthesis of much longer and more complex
cyclic peptides.
PMID- 26421992
TI - Synthesis and preliminary biological evaluation of a small library of hybrid
compounds based on Ugi isocyanide multicomponent reactions with a marine natural
product scaffold.
AB - A mixture-based combinatorial library of five Ugi adducts (4-8) incorporating
known antitubercular and antimalarial pharmacophores was successfully
synthesized, starting from the naturally occurring diisocyanide 3, via parallel
Ugi four-center three-component reactions (U-4C-3CR). The novel alpha-acylamino
amides obtained were evaluated for their antiinfective potential against
laboratory strains of Mycobacterium tuberculosis H37Rv and chloroquine
susceptible 3D7 Plasmodium falciparum. Interestingly, compounds 4-8 displayed
potent in vitro antiparasitic activity with higher cytotoxicity in comparison to
their diisocyanide precursor 3, with the best compound exhibiting an IC50 value
of 3.6 nM. Additionally, these natural product inspired hybrids potently
inhibited in vitro thromboxane B2 (TXB2) and superoxide anion (O2(-)) generation
from Escherichia coli lipopolysaccharide (LPS)-activated rat neonatal microglia,
with concomitant low short-term toxicity.
PMID- 26421994
TI - Site-specific incorporation of a fluorescent terphenyl unnatural amino acid.
AB - The site-specific incorporation of unnatural amino acids into proteins has a wide
range of biological implications. Of particular interest is the incorporation of
fluorescent probes as a mechanism to track protein function, transport, and
folding. Thus, the development of a novel system for the incorporation of new
fluorescent unnatural amino acids has significant utility. Specifically, we have
elucidated an aminoacyl-tRNA synthetase capable of recognizing a terphenyl UAA
derivative, and charging a cognate tRNA with this amino acid for protein
incorporation. Moreover, we have successfully incorporated this fluorescent UAA
into GFP at several key residues, demonstrating a novel means to modulate
fluorescence within the protein.
PMID- 26421993
TI - Structure-guided discovery of 2-aryl/pyridin-2-yl-1H-indole derivatives as potent
and selective hepsin inhibitors.
AB - Hepsin, a type II transmembrane serine protease, is upregulated in prostate
cancer and known to be involved in the progression of metastasis. Here we report
a structure-guided approach, which resulted in the discovery of 2-aryl/pyridin-2
yl-1H-indole derivatives as potent and selective inhibitors of hepsin. Potent and
selective inhibition of hepsin by compound 8 is likely due to interactions of the
amidine group at the S1 site with the cyclohexyl ring from the 2-aryl group
projecting towards the S1' site and the tert-hydroxyl group interacting with
His57 side-chain as revealed by X-ray crystallography. Compounds 8 and 10, showed
Ki of 0.1 MUM for hepsin, and exhibited inhibition of invasion and migration of
hepsin-overexpressing cell line. Compounds described here could serve as useful
tool reagents to investigate the role of hepsin as a potential therapeutic target
in cancer.
PMID- 26421995
TI - Design, synthesis and biological evaluation of 3-aryl-rhodanine benzoic acids as
anti-apoptotic protein Bcl-2 inhibitors.
AB - A new class of 3-aryl-rhodanine benzoic acid derivatives were designed,
synthesized, and evaluated for their inhibition activities against anti-apoptotic
Bcl-2 proteins. The potent compounds 33 and 41 bound to Bcl-2 with submicromolar
Ki values and had selectivities to Bcl-2/Mcl-1 over Bcl-xL. In addition, they
exhibited obvious antiproliferative activities in three human tumor cell lines
(MDA-MB-231, K562 and PC-3).
PMID- 26421997
TI - Unpaid work in health economic evaluations.
AB - Given its societal importance, unpaid work should be included in economic
evaluations of health care technology aiming to take a societal perspective.
However, in practice this does not often appear to be the case. This paper
provides an overview of the current place of unpaid work in economic evaluations
in theory and in practice. It does so first by summarizing recommendations
regarding the inclusion of unpaid labor reported in health economic textbooks and
national guidelines for economic evaluations. In total, three prominent health
economic text-books were studied and 28 national health economic guidelines. The
paper, moreover, provides an overview of the instruments available to measure
lost unpaid labor and reports on a review of the place of unpaid labor in applied
economic evaluations in the area of rheumatoid arthritis. The review was
conducted by examining methodology of evaluations published between 1 March 2008
and 1 March 2013. The results of this study show that little guidance is offered
regarding the inclusion of unpaid labor in economic evaluations in textbooks and
guidelines. The review identified five productivity costs instruments including
questions about unpaid work and 33 economic evaluations of treatments for
rheumatoid arthritis of which only one included unpaid work. The results indicate
that unpaid work is rarely included in applied economic evaluations of treatments
for rheumatoid arthritis, despite this disease expecting to be associated with
lost unpaid work. Given the strong effects of certain diseases and treatments on
the ability to perform unpaid work, unpaid work currently receives less attention
in economic evaluations than it deserves.
PMID- 26421996
TI - Panaxydol, a component of Panax ginseng, induces apoptosis in cancer cells
through EGFR activation and ER stress and inhibits tumor growth in mouse models.
AB - We reported previously that panaxydol, a component of Panax ginseng roots,
induced mitochondria-mediated apoptosis preferentially in transformed cells. This
study demonstrates that EGFR activation and the resulting ER stress mediate
panaxydol-induced apoptosis, and that panaxydol suppresses in vivo tumor growth
in syngeneic and xenogeneic mouse tumor models. In addition, we elucidated that
CaMKII and TGF-beta-activated kinase (TAK1) participate in p38/JNK activation by
elevated cytoplasmic Ca(2+) concentration ([Ca(2+)]c). In MCF-7 cells, EGFR was
activated immediately after exposure to panaxydol, and this activation was
necessary for induction of apoptosis, suggesting that panaxydol might be a
promising anticancer candidate, especially for EGFR-addicted cancer. Activation
of PLCgamma followed EGFR activation, resulting in Ca(2+) release from the
endoplasmic reticulum (ER) via inositol triphosphate and ryanodine receptors. ER
Ca(2+) release triggered mitochondrial Ca(2+) uptake indirectly through oxidative
stress and ensuing ER stress. Elevated [Ca(2+)]c triggered sequential activation
of calmodulin/CaMKII, TAK1 and p38/JNK. As shown previously, p38 and JNK activate
NADPH oxidase. Here, it was shown that the resulting oxidative stress triggered
ER stress. Among the three signaling branches of the unfolded protein response,
protein kinase R-like ER kinase (PERK), but not inositol-requiring enzyme 1 or
activating transcription factor 6, played a role in transmitting the apoptosis
signal. PERK induced C/EBP homologous protein (CHOP), and CHOP elevated Bim
expression, initiating mitochondrial Ca(2+) uptake and apoptosis. In summary, we
identified roles of EGFR, the CAMKII-TAK1-p38/JNK pathway, and ER stress in
panaxydol-induced apoptosis and demonstrated the in vivo anticancer effect of
panaxydol.
PMID- 26421999
TI - Sustained Increased Entry of Medical Students into Surgical Careers: A Student
Led Approach.
AB - OBJECTIVE: To determine whether a surgical interest group run entirely by
preclinical students can influence medical students to enter general surgery
residency programs. DESIGN: Matriculation rates into general surgery and
affiliated subspecialties from Columbia University College of Physicians and
Surgeons residency match lists were compared to National Residency Match Program
data for all U.S. senior students from 2006 to 2014. SETTING: The Columbia
University College of Physicians and Surgeons. RESULTS: After establishing the
interest group, entrance rates into general surgery programs tripled from the
early 2000s to more than 12% of 2006 Columbia University College of Physicians
and Surgeons graduates. After 8 years, our data illustrate sustained results,
with more than 8% of students entering surgical residencies, significantly higher
than the National Residency Match Program's average (p < 0.025). CONCLUSIONS:
Surgical interest groups spark early and lasting interest in surgery that may
influence residency decisions. Moreover, these programs can be successfully run
entirely by preclinical students and implemented in other institutions.
PMID- 26422000
TI - Attending Surgeons' Leadership Style in the Operating Room: Comparing Junior
Residents' Experiences and Preferences.
AB - PURPOSE: Recent studies have focused on surgeons' nontechnical skills in the
operating room (OR), especially leadership. In an attempt to identify trainee
preferences, we explored junior residents' opinions about the OR leadership style
of teaching faculty. METHODS: Overall, 20 interns and 20 mid-level residents
completed a previously validated survey on the style of leadership they
encountered, the style they preferred to receive, and the style they personally
employed in the OR. In all, 4 styles were explored; authoritative: leader makes
decisions and communicates them firmly; explanatory: leader makes decisions
promptly, but explains them fully; consultative: leader consults with trainees
when important decisions are made, and delegative: leader puts the problem before
the group and makes decisions by majority opinion. Comparisons were completed
using chi-square analysis. RESULTS: Junior resident preference for leadership
style of attending surgeons in the OR differed from what they encountered.
Overall, 62% of residents encountered an authoritative leadership style; however,
only 9% preferred this (p < 0.001). Instead, residents preferred explanatory
(53%) or consultative styles (41%). Preferences differed by postgraduate year.
Although 40% of interns preferred a consultative style, 50% of mid-level
residents preferred explanatory leadership. CONCLUSIONS: Junior resident
preference of leadership style in the OR differs from what they actually
encounter. This has the potential to create unwanted tension and may erode team
performance. Awareness of this difference provides an opportunity for an
educational intervention directed at both attendings and trainees.
PMID- 26422001
TI - The Effect of Instrumentation on Suture Tensile Strength and Knot Pullout
Strength of Common Suture Materials.
AB - OBJECTIVE: To determine the effect of instrumentation of suture material on knot
security and tensile strength. STUDY DESIGN: In all, 5 types of suture material
were used; 10 knots were tied without any instrumentation and 10 knots were tied
with a hemostat holding tension on the first throw while the second throw was
made for each suture type. Each group was tested to failure with the maximum load
and mode of failure recorded. The maximum load between groups of each suture type
was compared; frequency of failure through knot slippage vs material fracture was
also compared between groups. RESULTS: There was no significant difference
observed in the maximum load to failure for any suture type between instrumented
and noninstrumented groups. Additionally, there was no difference between any
instrumented and noninstrumented groups for material failure vs failure due to
knot slippage. CONCLUSIONS: Instrumentation of suture material during two-hand
tying does not affect the strength of suture material or knot security.
PMID- 26421998
TI - Site-Directed Mutagenesis of Surface-Exposed Lysine Residues Leads to Improved
Transduction by AAV2, But Not AAV8, Vectors in Murine Hepatocytes In Vivo.
AB - The ubiquitin-proteasome pathway plays a critical role in the intracellular
trafficking of recombinant adeno-associated virus 2 (AAV2) vectors, which
negatively impacts the transduction efficiency of these vectors. Because
ubiquitination occurs on lysine (K) residues, we performed site-directed
mutagenesis where we replaced each of 10 surface-exposed K residues (K258, K490,
K507, K527, K532, K544, K549, K556, K665, and K706) with glutamic acid (E)
because of similarity of size and lack of recognition by modifying enzymes. The
transduction efficiency of K490E, K544E, K549E, and K556E scAAV2 vectors
increased in HeLa cells in vitro up to 5-fold compared with wild-type (WT) AAV2
vectors, with the K556E mutant being the most efficient. Intravenous delivery of
WT and K-mutant ssAAV2 vectors further corroborated these results in murine
hepatocytes in vivo. Because AAV8 vectors transduce murine hepatocytes
exceedingly well, and because some of the surface-exposed K residues are
conserved between these serotypes, we generated and tested two single mutants
(K547E and K569E), and one double-mutant (K547 + 569E) AAV8 vector. However, no
significant increase in the transduction efficiency of any of these mutant AAV8
vectors was observed in murine hepatocytes in vivo. These studies suggest that
although targeting the surface-exposed K residues is yet another strategy to
improve the transduction efficiency of AAV vectors, phenotypic outcome is
serotype specific.
PMID- 26422002
TI - Reducing involuntary memory by interfering consolidation of stressful auditory
information: A pilot study.
AB - BACKGROUND AND OBJECTIVES: Intrusive emotional memories were induced by aversive
auditory stimuli and modulated with cognitive tasks performed post-encoding
(i.e., during consolidation). METHOD: A between-subjects design was used with
four conditions; three consolidation-interference tasks (a visuospatial and two
verbal interference tasks) and a no-task control condition. Forty-one
participants listened to a soundtrack depicting traumatic scenes (e.g., police
brutality, torture and rape). Immediately after listening to the soundtrack, the
subjects completed a randomly assigned task for 10 min. Intrusions from the
soundtrack were reported in a diary during the following seven-day period.
RESULTS: In line with a modality-specific approach to intrusion modulation,
auditory intrusions were reduced by verbal tasks compared to both a no-task and a
visuospatial interference task.. LIMITATIONS: The study did not control for
individual differences in imagery ability which may be a feature in intrusion
development. CONCLUSIONS: The results provide an increased understanding of how
intrusive mental images can be modulated which may have implications for
preventive treatment..
PMID- 26422003
TI - Multifunctional Fe2O3@PPy-PEG nanocomposite for combination cancer therapy with
MR imaging.
AB - In recent years, magnetic hyperthermia nanoparticles have drawn great attention
for cancer therapy because they have no limitation of tissue penetration during
the therapy process. In this study, cubic nanoporous Fe2O3 nanoparticles derived
from cubic Prussian blue nanoparticles were used as magnetic cores to generate
heat by alternating the current magnetic field (AMF) for killing cancer cells. In
addition, polypyrrole (PPy) was coated on the surfaces of the cubic Fe2O3
nanoparticles to load doxorubicin hydrochloride (DOX). The PEG component was then
physically adsorbed onto the surfaces of the nanoparticles, resulting in a
Fe2O3@PPy-DOX-PEG nanocomposite. The nanocomposite was triggered by acid stimulus
and AMF to release DOX, resulting in a remarkable combination therapeutic effect
via chemotherapy and magnetic hyperthermia. Furthermore, the nanocomposite could
realize magnetic resonance imaging (MRI) due to the magnetic core structure. The
study provides an alternative for the development of new nanocomposites for
combination cancer therapy with MR imaging in vivo.
PMID- 26422004
TI - Prenatal Cannabis and Tobacco Exposure in Relation to Brain Morphology: A
Prospective Neuroimaging Study in Young Children.
AB - BACKGROUND: Cannabis use during pregnancy has been associated with negative
behavioral outcomes and psychopathology in offspring. However, there has been
little research evaluating alterations in brain structure as a result of maternal
cannabis use. In this prospective study, we investigated the association between
prenatal cannabis exposure and brain morphology in young children. METHODS: We
matched 96 children prenatally exposed to tobacco only (without cannabis) with
113 unexposed control subjects on the basis of age and gender and subsequently
selected 54 children exposed to prenatal cannabis (mostly combined with tobacco
exposure). These children (aged 6 to 8 years) were part of a population-based
study in the Netherlands, the Generation R Study, and were followed from
pregnancy onward. We assessed brain volumetric measures and cortical thickness in
magnetic resonance imaging scans using FreeSurfer. We performed vertexwise
analyses in FreeSurfer and linear regression analyses adjusting for relevant
covariates using Statistical Package for the Social Sciences. RESULTS: Prenatal
cannabis exposure was not associated with global brain volumes, such as total
brain volume, gray matter volume, or white matter volume. However, prenatal
cannabis exposure was associated with differences in cortical thickness: compared
with nonexposed control subjects, cannabis-exposed children had thicker frontal
cortices. Prenatal tobacco exposure compared with nonexposed control subjects was
associated with cortical thinning, primarily in the superior frontal and superior
parietal cortices. CONCLUSIONS: Our findings suggest an association between
prenatal cannabis exposure and cortical thickness in children. Further research
is needed to explore the causal nature of this association.
PMID- 26422006
TI - Inhibiting the Inflammasome: A Chemical Perspective.
AB - Inflammasomes are high molecular weight complexes that sense and react to injury
and infection. Their activation induces caspase-1 activation and release of
interleukin-1beta, a pro-inflammatory cytokine involved in both acute and chronic
inflammatory responses. There is increasing evidence that inflammasomes,
particularly the NLRP3 inflammasome, act as guardians against noninfectious
material. Inappropriate activation of the NLRP3 inflammasome contributes to the
progression of many noncommunicable diseases such as gout, type II diabetes, and
Alzheimer's disease. Inhibiting the inflammasome may significantly reduce
damaging inflammation and is therefore regarded as a therapeutic target.
Currently approved inhibitors of interleukin-1beta are rilonacept, canakinumab,
and anakinra. However, these proteins do not possess ideal pharmacokinetic
properties and are unlikely to easily cross the blood-brain barrier. Because
inflammation can contribute to neurological disorders, this review focuses on the
development of small-molecule inhibitors of the NLRP3 inflammasome.
PMID- 26422007
TI - The 4th Bi-annual international African-Caribbean Cancer Consortium conference:
building capacity to address cancer health disparities in populations of African
descent.
AB - This is a brief summary of the 4(th) International Meeting of the African
Caribbean Cancer Consortium (AC3), organized and sponsored by Fox Chase Cancer
Center (FCCC), and held on July 21-22, 2012 at the Lincoln University Graduate
Center, Lincoln Plaza, Philadelphia, Pennsylvania. AC3 investigators gathered in
Philadelphia, PA to present the results of our ongoing collaborative research
efforts throughout the African Diaspora. The general theme addressed cancer
health disparities and presentations represented all cancer types. However, there
was particular emphasis on women's cancers, related to human papillomavirus (HPV)
and human immunodeficiency virus (HIV) infections.
PMID- 26422005
TI - Neuroanatomic Differences Associated With Stress Susceptibility and Resilience.
AB - BACKGROUND: We examined the neurobiological mechanisms underlying stress
susceptibility using structural magnetic resonance imaging and diffusion tensor
imaging to determine neuroanatomic differences between stress-susceptible and
resilient mice. We also examined synchronized anatomic differences between brain
regions to gain insight into the plasticity of neural networks underlying stress
susceptibility. METHODS: C57BL/6 mice underwent 10 days of social defeat stress
and were subsequently tested for social avoidance. For magnetic resonance
imaging, brains of stressed (susceptible, n = 11; resilient, n = 8) and control
(n = 12) mice were imaged ex vivo at 56 um resolution using a T2-weighted
sequence. We tested for behavior-structure correlations by regressing social
avoidance z-scores against local brain volume. For diffusion tensor imaging,
brains were scanned with a diffusion-weighted fast spin echo sequence at 78 MUm
isotropic voxels. Structural covariance was assessed by correlating local volume
between brain regions. RESULTS: Social avoidance correlated negatively with local
volume of the cingulate cortex, nucleus accumbens, thalamus, raphe nuclei, and
bed nucleus of the stria terminals. Social avoidance correlated positively with
volume of the ventral tegmental area (VTA), habenula, periaqueductal gray,
cerebellum, hypothalamus, and hippocampal CA3. Fractional anisotropy was
increased in the hypothalamus and hippocampal CA3. We observed synchronized
anatomic differences between the VTA and cingulate cortex, hippocampus and VTA,
hippocampus and cingulate cortex, and hippocampus and hypothalamus. These
correlations revealed different structural covariance between brain regions in
susceptible and resilient mice. CONCLUSIONS: Stress-integrative brain regions
shape the neural architecture underlying individual differences in susceptibility
and resilience to chronic stress.
PMID- 26422008
TI - Molecular Binding Mechanism of TtgR Repressor to Antibiotics and Antimicrobials.
AB - A disturbing phenomenon in contemporary medicine is the prevalence of multidrug
resistant pathogenic bacteria. Efflux pumps contribute strongly to this
antimicrobial drug resistance, which leads to the subsequent failure of clinical
treatments. The TtgR protein of Pseudomonas putida is a HTH-type transcriptional
repressor that controls expression of the TtgABC efflux pump, which is the main
contributor to resistance against several antimicrobials and toxic compounds in
this microbe. One of the main strategies to modulate the bacterial resistance is
the rational modification of the ligand binding target site. We report the design
and characterization of four mutants-TtgRS77A, TtgRE78A, TtgRN110A and TtgRH114A
at the active ligand binding site. The biophysical characterization of the
mutants, in the presence and in the absence of different antimicrobials, revealed
that TtgRN110A is the variant with highest thermal stability, under any of the
experimental conditions tested. EMSA experiments also showed a different
dissociation pattern from the operator for TtgRN110A, in the presence of several
antimicrobials, making it a key residue in the TtgR protein repression mechanism
of the TtgABC efflux pump. We found that TtgRE78A stability is the most affected
upon effector binding. We also probe that one mutation at the C-terminal half of
helix-alpha4, TtgRS77A, provokes a severe protein structure distortion,
demonstrating the important role of this residue in the overall protein structure
and on the ligand binding site. The data provide new information and deepen the
understanding of the TtgR-effector binding mechanism and consequently the TtgABC
efflux pump regulation mechanism in Pseudomonas putida.
PMID- 26422009
TI - Effects of Dietary Crude Protein Levels and Cysteamine Supplementation on Protein
Synthetic and Degradative Signaling in Skeletal Muscle of Finishing Pigs.
AB - Dietary protein levels and cysteamine (CS) supplementation can affect growth
performance and protein metabolism of pigs. However, the influence of dietary
protein intake on the growth response of CS-treated pigs is unclear, and the
mechanisms involved in protein metabolism remain unknown. Hence, we investigated
the interactions between dietary protein levels and CS supplementation and the
effects of dietary crude protein levels and CS supplementation on protein
synthetic and degradative signaling in skeletal muscle of finishing pigs. One
hundred twenty barrows (65.84 +/- 0.61 kg) were allocated to a 2 * 2 factorial
arrangement with five replicates of six pigs each. The primary variations were
dietary crude protein (CP) levels (14% or 10%) and CS supplemental levels (0 or
700 mg/kg). The low-protein (LP) diets (10% CP) were supplemented with enough
essential amino acids (EAA) to meet the NRC AA requirements of pigs and maintain
the balanced supply of eight EAA including lysine, methionine, threonine,
tryptophan, valine, phenylalanine, isoleucine, and leucine. After 41 days, 10
pigs per treatment were slaughtered. We found that LP diets supplemented with EAA
resulted in decreased concentrations of plasma somatostatin (SS) (P<0.01) and
plasma urea nitrogen (PUN) (P<0.001), while dietary protein levels did not affect
other traits. However, CS supplementation increased the average daily gain
(P<0.001) and lean percentage (P<0.05), and decreased the feed conversion ratio
(P<0.05) and back fat (P<0.05). CS supplementation also increased the
concentrations of plasma insulin-like growth factor 1 (IGF-1) (P<0.001), and
reduced the concentrations of leptin, SS, and PUN (P<0.001). Increased mRNA
abundance of Akt1 and IGF-1 signaling (P<0.001) and decreased mRNA abundance of
Forkhead Box O (FOXO) 4 (P<0.01) and muscle atrophy F-box (P<0.001) were observed
in pigs receiving CS. Additionally, CS supplementation increased the protein
levels for the phosphorylated mammalian target of rapamycin (mTOR), eIF-4E
binding protein 1, and ribosomal protein S6 kinase 1 (P<0.001). There were no
interactions between dietary protein levels and CS supplementation for all
traits. In conclusion, dietary protein levels and CS supplementation influenced
growth and protein metabolism through independent mechanisms in pigs. In
addition, LP diets supplemented with EAA did not affect growth performance and
other traits except the concentrations of SS and PUN probably through maintenance
of protein synthesis and degradation signaling. Moreover, CS supplementation
improved growth performance by increasing plasma IGF-1 concentrations possibly
through alterations of mTOR and Akt/FOXO signaling pathways in skeletal muscle of
finishing pigs.
PMID- 26422010
TI - Evaluation of the Anti-Inflammatory, Antioxidant and Immunomodulatory Effects of
the Organic Extract of the Red Sea Marine Sponge Xestospongia testudinaria
against Carrageenan Induced Rat Paw Inflammation.
AB - Marine sponges are found to be a rich source of bioactive compounds which show a
wide range of biological activities including antiviral, antibacterial, and anti
inflammatory activities. This study aimed to investigate the possible anti
inflammatory, antioxidant and immunomodulator effects of the methanolic extract
of the Red Sea marine sponge Xestospongia testudinaria. The chemical composition
of the Xestospongia testudinaria methanolic extract was determined using Gas
chromatography-mass spectroscopy (GC-MS) analysis. DPPH (2, 2-diphenyl-1-picryl
hydrazyl) was measured to assess the antioxidant activity of the sponge extract.
Carrageenan-induced rat hind paw edema was adopted in this study. Six groups of
rats were used: group1: Control, group 2: Carrageenan, group 3: indomethacin (10
mg/kg), group 4-6: Xestospongia testudinaria methanolic extract (25, 50, and 100
mg/kg). Evaluation of the anti-inflammatory activity was performed by both
calculating the percentage increase in paw weight and hisopathologically.
Assessment of the antioxidant and immunomodulatory activity was performed. GC-MS
analysis revealed that there were 41 different compounds present in the
methanolic extract. Sponge extract exhibited antioxidant activity against DPPH
free radicals. Xestospongia testudinaria methanolic extract (100 mg/kg)
significantly decreased % increase in paw weight measured at 1, 2, 3 and 4 h
after carrageenan injection. Histopathologically, the extract caused a marked
decrease in the capillary congestion and inflammatory cells infiltrate. The
extract decreased paw malondialdehyde (MDA) and nitric oxide (NO) and increased
the reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT)
activity. It also decreased the inflammatory cytokines, tumor necrosis factor
alpha (TNF-alpha), interleukin-1 beta(IL-1beta) and IL-6. The results of this
study demonstrated the anti-inflammatory, antioxidant, and immunomodulatory
effects of the methanolic extract of the Red Sea sponge Xestospongia testudinaria
(100 mg/kg).
PMID- 26422013
TI - Nonfamilial Chronic Serum Alpha-Fetoprotein Increase in a Patient With Clinical
Stage I Seminoma.
PMID- 26422012
TI - Modelling Future Coronary Heart Disease Mortality to 2030 in the British Isles.
AB - OBJECTIVE: Despite rapid declines over the last two decades, coronary heart
disease (CHD) mortality rates in the British Isles are still amongst the highest
in Europe. This study uses a modelling approach to compare the potential impact
of future risk factor scenarios relating to smoking and physical activity levels,
dietary salt and saturated fat intakes on future CHD mortality in three
countries: Northern Ireland (NI), Republic of Ireland (RoI) and Scotland.
METHODS: CHD mortality models previously developed and validated in each country
were extended to predict potential reductions in CHD mortality from 2010
(baseline year) to 2030. Risk factor trends data from recent surveys at baseline
were used to model alternative future risk factor scenarios: Absolute decreases
in (i) smoking prevalence and (ii) physical inactivity rates of up to 15% by
2030; relative decreases in (iii) dietary salt intake of up to 30% by 2030 and
(iv) dietary saturated fat of up to 6% by 2030. Probabilistic sensitivity
analyses were then conducted. RESULTS: Projected populations in 2030 were 1.3,
3.4 and 3.9 million in NI, RoI and Scotland respectively (adults aged 25-84). In
2030: assuming recent declining mortality trends continue: 15% absolute
reductions in smoking could decrease CHD deaths by 5.8-7.2%. 15% absolute
reductions in physical inactivity levels could decrease CHD deaths by 3.1-3.6%.
Relative reductions in salt intake of 30% could decrease CHD deaths by 5.2-5.6%
and a 6% reduction in saturated fat intake might decrease CHD deaths by some 7.8
9.0%. These projections remained stable under a wide range of sensitivity
analyses. CONCLUSIONS: Feasible reductions in four cardiovascular risk factors
(already achieved elsewhere) could substantially reduce future coronary deaths.
More aggressive polices are therefore needed in the British Isles to control
tobacco, promote healthy food and increase physical activity.
PMID- 26422011
TI - Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk.
AB - Environmental exposure to heavy metals is a potentially modifiable risk factor
for preeclampsia (PE). Toxicologically, there are known interactions between the
toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc
(Zn), as these metals can protect against the toxicity of Cd. As they relate to
preeclampsia, the interaction between Cd and these essential metals is unknown.
The aims of the present study were to measure placental levels of Cd, Se, and Zn
in a cohort of 172 pregnant women from across the southeast US and to examine
associations of metals levels with the odds of PE in a nested case-control
design. Logistic regressions were performed to assess odds ratios (OR) for PE
with exposure to Cd controlling for confounders, as well as interactive models
with Se or Zn. The mean placental Cd level was 3.6 ng/g, ranging from 0.52 to
14.5 ng/g. There was an increased odds ratio for PE in relationship to placental
levels of Cd (OR = 1.5; 95% CI: 1.1-2.2). The Cd-associated OR for PE increased
when analyzed in relationship to lower placental Se levels (OR = 2.0; 95% CI: 1.1
3.5) and decreased with higher placental Se levels (OR = 0.98; 95% CI: 0.5-1.9).
Similarly, under conditions of lower placental Zn, the Cd-associated OR for PE
was elevated (OR = 1.8; 95% CI: 0.8-3.9), whereas with higher placental Zn it was
reduced (OR = 1.3; 95% CI: 0.8-2.0). Data from this pilot study suggest that
essential metals may play an important role in reducing the odds of Cd-associated
preeclampsia and that replication in a larger cohort is warranted.
PMID- 26422014
TI - Tumor Vascularity in Renal Masses: Correlation of Arterial Spin-Labeled and
Dynamic Contrast-Enhanced Magnetic Resonance Imaging Assessments.
AB - Arterial spin-labeled (ASL) and dynamic contrast-enhanced (DCE) magnetic
resonance imaging (MRI) have been proposed to quantitatively assess vascularity
in renal cell carcinoma (RCC). However, there are intrinsic differences between
these 2 imaging methods, such as the relative contribution of vascular
permeability and blood flow to signal intensity for DCE MRI. We found a
correlation between ASL perfusion and the DCE-derived volume transfer constant
and rate constant parameters in renal masses > 2 cm in size and these measures
correlated with microvessel density in clear cell RCC. BACKGROUND: The objective
of this study was to investigate potential correlations between perfusion using
arterial spin-labeled (ASL) magnetic resonance imaging (MRI) and dynamic contrast
enhanced (DCE) MRI-derived quantitative measures of vascularity in renal masses >
2 cm and to correlate these with microvessel density (MVD) in clear cell renal
cell carcinoma (ccRCC). PATIENTS AND METHODS: Informed written consent was
obtained from all patients before imaging in this Health Insurance Portability
and Accountability Act-compliant, institutional review board-approved,
prospective study. Thirty-six consecutive patients scheduled for surgery of a
known renal mass > 2 cm underwent 3T ASL and DCE MRI. ASL perfusion measures
(PASL) of mean, peak, and low perfusion areas within the mass were correlated to
DCE-derived volume transfer constant (K(trans)), rate constant (Kep), and
fractional volume of the extravascular extracellular space (Ve) in the same
locations using a region of interest analysis. MRI data were correlated to MVD
measures in the same tumor regions in ccRCC. Spearman correlation was used to
evaluate the correlation between PASL and DCE-derived measurements, and MVD. P <
.05 was considered statistically significant. RESULTS: Histopathologic diagnosis
was obtained in 36 patients (25 men; mean age 58 +/- 12 years). PASL correlated
with K(trans) (rho = 0.48 and P = .0091 for the entire tumor and rho = 0.43 and P
= .03 for the high flow area, respectively) and Kep (rho = 0.46 and P = .01 for
the entire tumor and rho = 0.52 and P = .008 for the high flow area,
respectively). PASL (rho = 0.66; P = .0002), K(trans) (rho = 0.61; P = .001), and
Kep (rho = 0.64; P = .0006) also correlated with MVD in high and low perfusion
areas in ccRCC. CONCLUSION: PASL correlated with the DCE-derived measures of
vascular permeability and flow, K(trans) and Kep, in renal masses > 2 cm in size.
Both measures correlated to MVD in clear cell histology.
PMID- 26422015
TI - Epidemiological Characteristics and Spatial-Temporal Clusters of Hand, Foot, and
Mouth Disease in Zhejiang Province, China, 2008-2012.
AB - Hand, foot and mouth disease (HFMD) is one of the major public health concerns in
China. Being the province with high incidence rates of HFMD, the epidemiological
features and the spatial-temporal patterns of Zhejiang Province were still
unknown. The objective of this study was to investigate the epidemiological
characteristics and the high-incidence clusters, as well as explore some
potential risk factors. The surveillance data of HFMD during 2008-2012 were
collected from the communicable disease surveillance network system of Zhejiang
Provincial Center for Disease Control and Prevention. The distributions of age,
gender, occupation, season, region, pathogen's serotype and disease severity were
analyzed to describe the epidemiological features of HFMD in Zhejiang Province.
Seroprevalence survey for human enterovirus 71 (EV71) in 549 healthy children of
Zhejiang Province was also performed, as well as 27 seroprevalence publications
between 1997 and 2015 were summarized. The spatial-temporal methods were
performed to explore the clusters at county level. Furthermore, pathogens'
serotypes such as EV71 and coxsackievirus A16 (Cox A16) and meteorological
factors were analyzed to explore the potential factors associated with the
clusters. A total of 454,339 HFMD cases were reported in Zhejiang Province during
2008-2012, including 1688 (0.37%) severe cases. The annual average incidence rate
was 172.98 per 100,000 (ranged from 72.61 to 270.04). The male-to-female ratio
for mild cases was around 1.64:1, and up to 1.87:1 for severe cases. Of the total
cases, children aged under three years old and under five years old accounted for
almost 60% and 90%, respectively. Among all enteroviruses, the predominant
serotype was EV71 (49.70%), followed by Cox A16 (26.05%) and other enteroviruses
(24.24%) for mild cases. In severe cases, EV71 (82.85%) was the major causative
agent. EV71 seroprevalence survey in healthy children confirmed that occult
infection was common in children. Furthermore, literature summary for 26
seroprevalence studies during 1997-2015 confirmed that 0-5 years group showed
lowest level of EV71 seroprevalence (29.1% on average) compared to the elder
children (6-10 years group: 54.6%; 11-20 years group: 61.8%). Global positive
spatial autocorrelation patterns (Moran's Is>0.25, P<0.05) were discovered not
only for mild cases but also for severe cases, and local positive spatial
autocorrelation patterns were revealed for counties from the eastern coastal and
southern regions. The retrospective space-time cluster analysis also confirmed
these patterns. Risk factors analyses implied that more EV71 and less sunshine
were associated with the clusters of HFMD in Zhejiang Province. Our study
confirmed that Zhejiang Province was one of the highly epidemic provinces in
China and that the epidemiological characteristics of HFMD were similar to other
provinces. Occult infection in elder children and adults was one of the important
reasons why most HFMD cases were children aged under-five. Combining the results
of spatial autocorrelation analysis and the space-time cluster analysis, the
major spatial-temporal clusters were from the eastern coastal and southern
regions. The distribution of pathogens' serotypes and the level of sunshine could
be risk factors for, and serve as an early warning of, the outbreak of HFMD in
Zhejiang Province.
PMID- 26422016
TI - Detecting Lung Diseases from Exhaled Aerosols: Non-Invasive Lung Diagnosis Using
Fractal Analysis and SVM Classification.
AB - BACKGROUND: Each lung structure exhales a unique pattern of aerosols, which can
be used to detect and monitor lung diseases non-invasively. The challenges are
accurately interpreting the exhaled aerosol fingerprints and quantitatively
correlating them to the lung diseases. OBJECTIVE AND METHODS: In this study, we
presented a paradigm of an exhaled aerosol test that addresses the above two
challenges and is promising to detect the site and severity of lung diseases.
This paradigm consists of two steps: image feature extraction using sub-regional
fractal analysis and data classification using a support vector machine (SVM).
Numerical experiments were conducted to evaluate the feasibility of the breath
test in four asthmatic lung models. A high-fidelity image-CFD approach was
employed to compute the exhaled aerosol patterns under different disease
conditions. FINDINGS: By employing the 10-fold cross-validation method, we
achieved 100% classification accuracy among four asthmatic models using an ideal
108-sample dataset and 99.1% accuracy using a more realistic 324-sample dataset.
The fractal-SVM classifier has been shown to be robust, highly sensitive to
structural variations, and inherently suitable for investigating aerosol-disease
correlations. CONCLUSION: For the first time, this study quantitatively linked
the exhaled aerosol patterns with their underlying diseases and set the stage for
the development of a computer-aided diagnostic system for non-invasive detection
of obstructive respiratory diseases.
PMID- 26422017
TI - Marital Quality and Stress in Pregnancy Predict the Risk of Infectious Disease in
the Offspring: The Norwegian Mother and Child Cohort Study.
AB - OBJECTIVES: The aim of this study was to explore the degree to which couples'
relationship dissatisfaction and stressful life events during pregnancy predict
the risk of infectious disease in the offspring during their first year of life.
METHODS: Data were obtained from the Norwegian Mother and Child Cohort Study,
conducted by the Norwegian Institute of Public Health. Pregnant women completed
questionnaires in week 30 of pregnancy concerning the couples' relationship
satisfaction and stressful life events. In follow-up questionnaires, the women
reported whether their children (n = 74,801) had been subject to various
categories of infectious disease: the common cold, throat infection, bronchitis,
RS virus, pneumonia, pseudocroup, gastric flu, ear infection, conjunctivitis and
urinary tract infection. Reports from two age groups of infants were used.
Associations between the predictor and outcome variables were assessed via
logistic regression and linear regression analyses. RESULTS: Separate logistic
regression analyses for each disease and age group showed that prenatal
relationship dissatisfaction and stressful life events were significantly
associated with all reported categories of infectious disease. After controlling
for socioeconomic factors, social support, smoking, breastfeeding, maternal
depression, the sex of the offspring, and use of child care, 29 out of 32 tested
associations were statistically significant. Finally, multivariate linear
regression analyses showed that prenatal relationship dissatisfaction and
stressful life events were significantly associated with the frequency, as well
as the variety, of infectious disease in the offspring.
PMID- 26422018
TI - Cloud-Based Service Information System for Evaluating Quality of Life after
Breast Cancer Surgery.
AB - OBJECTIVE: Although recent studies have improved understanding of quality of life
(QOL) outcomes of breast conserving surgery, few have used longitudinal data for
more than two time points, and few have examined predictors of QOL over two
years. Additionally, the longitudinal data analyses in such studies rarely apply
the appropriate statistical methodology to control for censoring and inter
correlations arising from repeated measures obtained from the same patient pool.
This study evaluated an internet-based system for measuring longitudinal changes
in QOL and developed a cloud-based system for managing patients after breast
conserving surgery. METHODS: This prospective study analyzed 657 breast cancer
patients treated at three tertiary academic hospitals. Related hospital personnel
such as surgeons and other healthcare professionals were also interviewed to
determine the requirements for an effective cloud-based system for surveying QOL
in breast cancer patients. All patients completed the SF-36, Quality of Life
Questionnaire (QLQ-C30) and its supplementary breast cancer measure (QLQ-BR23) at
baseline, 6 months, 1 year, and 2 years postoperatively. The 95% confidence
intervals for differences in responsiveness estimates were derived by bootstrap
estimation. Scores derived by these instruments were interpreted by generalized
estimating equation before and after surgery. RESULTS: All breast cancer surgery
patients had significantly improved QLQ-C30 and QLQ-BR23 subscale scores
throughout the 2-year follow-up period (p<0.05). During the study period, QOL
generally had a negative association with advanced age, high Charlson comorbidity
index score, tumor stage III or IV, previous chemotherapy, and long post
operative LOS. Conversely, QOL was positively associated with previous
radiotherapy and hormone therapy. Additionally, patients with high scores for
preoperative QOL tended to have high scores for QLQ-C30, QLQ-BR23 and SF-36
subscales. Based on the results of usability testing, the five constructs were
rated on a Likert scale from 1-7 as follows: system usefulness (5.6+/-1.8), ease
of use (5.6+/-1.5), information quality (5.4+/-1.4), interface quality (5.5+/
1.4), and overall satisfaction (5.5+/-1.6). CONCLUSIONS: The current trend in
clinical medicine is applying therapies and interventions that improve QOL.
Therefore, a potentially vast amount of internet-based QOL data is available for
use in defining patient populations that may benefit from therapeutic
intervention. Additionally, before undergoing breast conserving surgery, patients
should be advised that their postoperative QOL depends not only on the success of
the surgery, but also on their preoperative functional status.
PMID- 26422019
TI - Ictal bruxism treated with temporal lobectomy.
PMID- 26422021
TI - Renal sympathetic denervation in uncontrolled arterial hypertension after
successful repair for aortic coarctation.
AB - BACKGROUND: Uncontrolled arterial hypertension is a frequent problem after
successful repair of CoA and has been attributed to increased central sympathetic
drive as well as a blunted baroreceptor reflex. RSD is a promising therapy to
reduce central sympathetic drive and improve baroreflex sensitivity. METHODS: 8
patients (age: 27+/-6 years) with previous surgical and/or percutaneous repair of
CoA, absence of any relevant restenosis (invasive gradient across the site of
previous treatment 3+/-4 mmHg) and resistant arterial hypertension (daytime
SBP>=140 mmHg on 24 hour ambulatory blood pressure measurements [ABPM] in spite
of the concurrent use of 3 antihypertensive agents of different classes or
intolerance to BP medications) were included. Bilateral RSD was performed using
the Symplicity FlexTM catheter (Medtronic, MN, USA). RESULTS: RSD was successful
in all patients with no procedural complications and no evidence for renal artery
stenosis 6 months post procedure. From baseline to 6 month follow-up, RSD was
followed by a significant reduction in average daytime systolic BP (150.4+/-7.8
to 143.1+/-8.0 mmHg; p=0.0117) as well as systolic BP throughout 24 h (146.8+/
7.3 vs. 140.5+/-7.8, p=0.04). CONCLUSION: The BP reductions observed in these
patients justify engaging in a larger clinical trial on the efficacy of RSD in
this specific type of secondary hypertension and bares the hope that RSD might
extend the currently very limited armory against arterial hypertension in young
adults with previous repair of CoA.
PMID- 26422022
TI - Physical activity and diet on quality of life and mortality: The importance of
meeting one specific or both behaviors.
PMID- 26422020
TI - Localization of CD8 T cell epitope within cardiac myosin heavy chain-alpha334-352
that induces autoimmune myocarditis in A/J mice.
AB - BACKGROUND: Cardiac myosin heavy chain-alpha (Myhc), an intracellular protein
expressed in the cardiomyocytes, has been identified as a major autoantigen in
cardiac autoimmunity. In our studies with Myhc334-352-induced experimental
autoimmune myocarditis in A/J mice (H-2a), we discovered that Myhc334-352,
supposedly a CD4 T cell epitope, also induced antigen-specific CD8 T cells that
transfer disease to naive animals. METHODS AND RESULTS: In our efforts to
identify the CD8 T cell determinants, we localized Myhc338-348 within the full
length-Myhc334-352, leading to four key findings. (1) By acting as a dual
epitope, Myhc338-348 induces both CD4 and CD8 T cell responses. (2) In a major
histocompatibility complex (MHC) class I-stabilization assay, Myhc338-348 was
found to bind H-2Dd-but not H-2Kk or H-2Ld-alleles. (3) The CD8 T cell response
induced by Myhc338-348 was antigen-specific, as evaluated by MHC class I/H-2Dd
dextramer staining. The antigen-sensitized T cells predominantly produced
interferon-gamma, the critical cytokine of effector cytotoxic T lymphocytes. (4)
Myhc338-348 was found to induce myocarditis in immunized animals as determined by
histology and magnetic resonance microscopy imaging. CONCLUSIONS: Our data
provide new insights as to how different immune cells can recognize the same
antigen and inflict damage through different mechanisms.
PMID- 26422023
TI - Histopathologic and Clinical Characterization of Thyroid Tumors Carrying the
BRAF(K601E) Mutation.
AB - BACKGROUND: While the association of the BRAF(V600E) mutation with aggressive
histopathological tumor features and clinical behavior has been extensively
studied in papillary thyroid carcinoma (PTC), the BRAF(K601E) mutation has not
been well characterized. This study reports what is currently the largest series
of BRAF(K601E) mutated thyroid nodules. METHODS: Histopathologic, cytologic, and
molecular reports over a period of seven years (June 2007 to June 2014) were
reviewed to identify thyroid cases with various types of BRAF mutations. All
cases positive for the BRAF(K601E) mutation were reviewed to confirm
histopathologic diagnosis and establish tumor variant, and clinical charts were
reviewed to obtain clinical characteristics and follow-up information. RESULTS:
The BRAF(K601E) mutation was identified in 39 patients and comprised 5.3% of all
BRAF mutations noted in thyroidectomy specimens. Twenty-seven out of 29 nodules
(93%) with BRAF(K601E) mutated tumors with surgical pathology results available
for review were PTC, one (3.4%) was a follicular thyroid carcinoma, and one
(3.4%) was a follicular adenoma. The majority of K601E-mutant PTCs (20 cases)
were follicular variant PTC. Encapsulation was present in all but one case, and
one case showed capsular invasion. Coexisting mutations overall were not
identified in BRAF(K601E) mutated thyroid nodules except in a case that exhibited
a complex K601E + T599I mutation and had a classic PTC phenotype. The majority of
K601E mutant nodules were T1 lesions (69%) and T2 lesions (28%) by TNM staging.
With a median follow-up of 19.6 months, no structural or biochemical recurrence
or metastases were found in patients with an isolated BRAF(K601E) mutation.
CONCLUSIONS: The BRAF(K601E) mutation is the second most common BRAF mutation
found in thyroid nodules. Unlike BRAF(V600E), the most common mutation, K601E is
strongly associated with follicular-patterned cancer, particularly with the
encapsulated follicular variant of PTC, and may also be found in follicular
thyroid carcinomas. Overall, BRAF(K601E) mutant tumors show better clinical
outcomes than BRAF(V600E) positive tumors, and preoperative BRAF(K601E) analysis
may provide important prognostic information for use in clinical management.
PMID- 26422024
TI - Research in nursing and new pathways based on SENPE.
PMID- 26422025
TI - Considerations about the manuscript published. Re: Chinese auriculotherapy to
improve quality of life of nursing team.
PMID- 26422026
TI - AUTHORS'S ANSWER.
PMID- 26422027
TI - Beliefs of older adults about their vulnerability to HIV/Aids, for the
construction of nursing diagnoses.
AB - OBJECTIVE: to know the beliefs of older adults about their vulnerability to
HIV/Aids, and to identify nursing diagnoses. METHOD: a field research implemented
in Family Health Units, in Joao Pessoa, Brazil. The sample included 250 older
adults of both genders with data collected from April to July of 2011. A Test of
Free Word Association was applied using the term HIV/Aids. A content analysis and
cross-mapping of the most frequent terms with the International Classification
for Nursing Practice, 2011 were performed. RESULTS: 202 terms were identified in
terms, with an overall frequency of 1156. Of the 202 terms, 16 were more frequent
and were used to construct the nursing diagnoses. The diagnoses identified were
knowledge about appropriate sexual behavior, ability for partial protection, fear
of death and hopelessness. CONCLUSION: understanding these beliefs drew from
knowledge about factors related to, vulnerability to HIV/Aids aimed at planning
health care actions for this population segment.
PMID- 26422028
TI - Multiprofessional residency in health: a document analysis of political
pedagogical projects.
AB - The object of the present study was collaborative education in multiprofessional
residency in health (MPRH) through interprofessional education (IPE). OBJECTIVE:
To analyze MPRH political pedagogical projects (PPP) developed in the state of
Sao Paulo and identify scenarios that are highly favorable to IPE. METHOD: This
was a descriptive exploratory study conducted through document analysis. RESULTS:
The analysis revealed a heterogeneous scenario regarding the curricula, didactic
and pedagogical organization, educational objectives, pedagogical matrices and
evaluation systems employed. One of the programs was identified as providing a
highly favorable setting for IPE. CONCLUSION: The analysis adequately evaluated
IPE in educational settings and found a highly favorable scenario for it,
identifying didactic, pedagogical, political and organizational MPRH elements.
PMID- 26422029
TI - The family living the child recovery process after hospital discharge.
AB - OBJECTIVE: to understand the meaning attributed by the family to its experience
in the recovery process of a child affected by an acute disease after discharge,
and to develop a theoretical model of this experience. Symbolic interactionism
was adopted as a theoretical reference, and grounded theory was adopted as a
methodological reference. METHOD: data were collected through interviews and
participant observation with 11 families, totaling 15 interviews. A theoretical
model consisting of two interactive phenomena was formulated from the analysis:
Mobilizing to restore functional balance and Suffering from the possibility of a
child's readmission. RESULTS: the family remains alert to identify early changes
in the child's health, in an attempt to avoid rehospitalization. CONCLUSION: the
effects of the disease and hospitalization continue to manifest in family
functioning, causing suffering even after the child's discharge and recovery.
PMID- 26422030
TI - Prevalence and factors associated with smoking among tobacco growers in southern
Brazil.
AB - OBJECTIVE: identify the prevalence and factors associated with smoking in tobacco
growers. METHOD: descriptive, cross-sectional research. Data collection occurred
in 2012 through household survey and interviews, including application of a
structured instrument and scale Fargestrom. RESULTS: there were 100 growers
included, average age of 46,9 +/- 10,8 years; 90(90%) married; 72(72%) white,
average family composition 3,7+/-1,1 people; median number of children 3(1-3),
and the average study time 6+/-2,5. The prevalence of smoking among tobacco
growers was 17%, which had less education (p=0.010) and fewer people in the
household (p=0.049). CONCLUSION: the prevalence of smoking among tobacco growers
was higher than the national average, but the nicotine dependence was low, which
can facilitate the smoking cessation process. Highlights the need to implement a
program to control smoking among tobacco growers.
PMID- 26422031
TI - Social representations about religion and spirituality.
AB - OBJECTIVE: to identify the social representations about the concepts of
spirituality and religion of of health teachers. METHOD: exploratory and
descriptive study, based on a qualitative approach. 25 subjects participated in
it. The following instruments were used to collect data: questionnaire to
identify the profile; questionnaire of free association, whose inducing words
were religion and spirituality, and an interview based on the scale FICA
(Puchalski, 2006). RESULTS: the representations about religion and spirituality,
for professors, are forged around the faith in God and it gives them meaning and
purpose to deal with the challenges of personal and professional living.
CONCLUSION: there are still barriers that need to be overcome with a view to a
comprehensive care. For this, it is essential to incorporate spirituality in the
process in the curricula of health courses.
PMID- 26422032
TI - Violence in the eye of adolescents: education intervention with Culture Circles.
AB - OBJECTIVE: to apply the methodology of Culture Circles on adolescents as a
strategy for health education of nurses in the construction of the collective
knowledge of the thematic violence. METHOD: action research type and qualitative
study. Participants were 11 adolescents from a public school in Recife, PE,
Brazil. Data production in Culture Circles included the participant observation
with field diary, photographic recording and filming, as well as the photovoice
technique. The analysis was performed by triangulating data in dialogue with the
literature. RESULTS: it was shown that the problematizing action provided by the
Culture Circle made possible to create situations in which adolescents felt
invited to critically refl ect on the phenomenon of violence in all its
complexity. CONCLUSION: the health education intervention, performed by Culture
Circles, added learning and mutual growth subsidizing nursing care actions that
excel at leadership and autonomy of adolescents.
PMID- 26422033
TI - Hypertension and Diabetes Mellitus Program evaluation on user's view.
AB - OBJECTIVES: to evaluate the program proposed by the Reorganization Care Plan for
Hypertension and Diabetes Mellitus on user's view, and describe aspects of the
trajectory of the participants correlating with the program's evaluation. METHOD:
evaluative study with a qualitative approach conducted in health units with the
Family Health Strategy, in a city of the metropolitan region of Curitiba, in the
period from September to March, 2012. A total of 30 adults with hypertension
and/or Diabetes mellitus were interviewed. Data were analyzed through content
analysis. RESULTS: Four categories were identified: Disease diagnosis; Reasons
for the program need; Knowledge of the program, and program evaluation.
CONCLUSION: there was the recognition of the orientations, and the monitoring of
activities developed, with emphasis in cost reduction for users.
PMID- 26422034
TI - Functional disability and socioeconomic and demographic factors in elderly.
AB - OBJECTIVE: to verify the prevalence of functional disability and associated
socioeconomic and demographic factors in elderly patients of Campina Grande/PB.
METHOD: cross-sectional study with elderly patients of both genders. The
variables associated with functional disability were assessed using Poisson
regression. RESULTS: A total of 420 elderly patients were included (68.1% women).
The highest prevalence of functional disability were found among females aged 80
or older, white, widowed, of economic classes D/E , who lived alone, with
frequency of contacts of up to 224 people and diversity of contacts of up to 14
people. After multivariate analysis, statistically significant association was
observed between functional disability, gender and age group. CONCLUSION: the
association between functional disability gender and age group is shown to be an
important guidance for health interventions since it will allow health services
to plan actions aiming to improve, maintain or restore the functional capacity of
the elderly population.
PMID- 26422035
TI - Nursing care management for children hospitalized with chronic conditions.
AB - OBJECTIVE: to understand the interactions of nurses managing nursing care for the
hospitalized child with a chronic condition. METHOD: Theoretical and
methodological references were used, Complex Thought and grounded theory,
respectively. In the study 18 subjects have participated arranged in three
groups: nurses, nursing technicians and family members. A semi-structured
interview was used as technique for data collection. The data analysis followed
three stages of coding: open, axial and selective. RESULTS: the category "Needing
to manage nursing care to the hospitalized child with chronic condition in
Pediatric Inpatient Unit" and their subcategories show the complex inter
subjective bindings established by nurses that support the practice of nursing
care management. CONCLUSION: There are difficulties for nursing professionals to
interact with the child's family and the dialogical
order/disorder/interaction/organization in the implementation of the management
process of care is.
PMID- 26422036
TI - Social support towards the necessity of caring after myocardial infarction.
AB - OBJECTIVE: to know the received or assisted social support by the family towards
the necessity of care after acute myocardial infarction. METHOD: qualitative and
exploratory research. Data collection was carried out through observation and
interviews with six families, from February to May, 2012. Data were also analyzed
based on the thematic analysis. RESULTS: three categories emerged: Immediate
social support; Mediate social support; Late social support. CONCLUSION: social
support follows the infarction trajectory, which attains the family members and
favors the support according to the needs of care in each lived moments by the
patient.
PMID- 26422037
TI - Post-accident work behavior in caring for people with HIV/Aids.
AB - OBJECTIVE: To identify post-accident conduct in the workplace by health
professionals in caring for people with HIV/Aids. METHOD: A qualitative and
descriptive research study with a socio-historical perspective (1986-2006),
performed in a reference hospital for infectious diseases in the State of Santa
Catarina. To collect data, interviews were conducted with oral history among 23
health workers and, for the treatment of data, Bardin's content analysis was
used. RESULTS: Post-accident behaviors emerged that included assessment, accident
records, chemoprophylaxis when necessary, support, monitoring of the injured
worker, and mainly psychological support. CONCLUSION: In situations in which the
accident could not be avoided, post-exposure behaviors were important biosecurity
strategies mentioned by health workers caring for patients with HIV/Aids, in the
sense of minimizing the possible transmission of the HIV virus.
PMID- 26422038
TI - Social representations of sexuality for the elderly.
AB - OBJECTIVE: to know the social representations of sexuality for the elderly, based
on the Social Representation Theory. METHOD: study performed in a Basic Family
Health Unit in Maracanau-CE, Brazil, with 30 elderly adults. Data were collected
from March through April of 2013, using the free word evocation technique. Data
were organized and processed using the EVOC 2000.software RESULTS: the subjects
evoked 150 words associated with the evocator word "sexuality". Out of these, 43
were different. At the possible core of the representation of sexuality for the
elderly, the following words were found: love, affection and respect. Sex,
companionship, understanding and coexistence composed the intermediate elements
of representation. CONCLUSION: the performed analyses pointed to love, respect
and affection as central elements that structured and organized the social
representation of sexuality in the elder years for the group studied.
PMID- 26422039
TI - Analysis of the decision-making process of nurse managers: a collective
reflection.
AB - OBJECTIVE: to analyze the decision-making model adopted by nurses from the
perspective of some decision-making process theories. METHOD: qualitative
approach, based on action research. Semi-structured questionnaires and seminars
were conducted from April to June 2012 in order to understand the nature of
decisions and the decision-making process of nine nurses in position of managers
at a public hospital in Southern Brazil. Data were subjected to content analysis.
RESULTS: data were classified in two categories: the current situation of
decision-making, which showed a lack of systematization; the construction and
collective decision-making, which emphasizes the need to develop a decision
making model. CONCLUSION: the decision-making model used by nurses is limited
because it does not consider two important factors: the limits of human
rationality, and the external and internal organizational environments that
influence and determine right decisions.
PMID- 26422040
TI - Health status and mental health in patients after percutaneous coronary
intervention.
AB - OBJECTIVE: to assess the association between perceived health status and the
mental health of patients submitted to percutaneous coronary intervention after
hospital discharge. METHOD: a quantitative and cross-sectional study involving
101 participants. The following instruments were used: a sociodemographic and
clinical characterization instrument, the Medical Outcomes Study 36-Item Short
Form Health Survey (SF-36), and the Hospital Anxiety and Depression Scale (HADS).
Participants were divided into three groups: no anxiety and no depression (G1);
anxiety or depression (G2); and both (G3). The ANOVA test was used for the
intergroup comparison of means on the SF-36 domains. RESULTS: There was an
association between perceived health status and mental health. The participants
in G1 presented higher scores in all SF-36 domains in comparison with
participants in G2 and G3. CONCLUSION: Participants with no anxiety and
depression presented better-perceived health status in comparison with those with
anxiety or depression, or both.
PMID- 26422041
TI - Direct cost of development and documentation of the nursing process.
AB - OBJECTIVE: identify the average direct cost (ADC) of the activities performed by
nursing professionals in the nursing process development and documentation at the
medical clinic of a teaching hospital. METHOD: 1040 activities were observed and
the ADC was calculated by multiplying the time spent by professionals by the unit
cost of direct labor. RESULTS: the ADC of patient admission was R$ 55.57
(SD=19.44); among the activities of patient follow-up, the assessment phase
documentation had the most significant ADC (R$ 17.70 - SD=14.60); the ADC of
descriptive records corresponded to R$ 1.21 (SD=1.21) and the ADC of the nursing
team for shift change was R$ 54.23 (SD=28.95). CONCLUSION: the study promotes
visibility of the work performed by nursing professionals in the development of
the nursing process, providing financial data to ensure consistent arguments for
proper resources to its feasibility.
PMID- 26422042
TI - Accuracy in inference of nursing diagnoses in heart failure patients.
AB - Heart failure (HF) is a common cause of hospitalization and requires accuracy in
clinical judgment and appropriate nursing diagnoses. OBJECTIVE: to determine the
accuracy of nursing diagnoses of fatigue, intolerance to activity and decreased
cardiac output in hospitalized HF patients. METHOD: descriptive study applied to
nurses with experience in NANDA-I and/or HF nursing diagnoses. Evaluation and
accuracy were determined by calculating efficacy (E), false negative (FN), false
positive (FP) and trend (T) measures. Nurses who showed acceptable inspection for
two diagnoses were selected. RESULTS: the nursing diagnosis of fatigue was the
most commonly mistaken diagnosis identified by the nursing evaluators.
DISCUSSION: the search for improving diagnostic accuracy reaffirms the need for
continuous and specific training to improve the diagnosis capability of nurses.
CONCLUSION: the training allowed the exercise of clinical judgment and better
accuracy of nurses.
PMID- 26422043
TI - Longevity according to life histories of the oldest-old.
AB - OBJECTIVE: to interpret life histories of the oldest-old in a community, grounded
on the perspective of the Active Aging and Life Course. METHOD: this is a
qualitative research. Participants included twenty seniors 80 years and older,
users of a Basic Health Unit. Life histories were collected and analyzed
according to the proposition of the Autobiographical Narrative Interview.
RESULTS: during the analytic process, elements found in the elders' present and
past arose, contributing to the development of a theoretical model: "Building
longevity along the life course." CONCLUSION: longevity is rooted in the past,
strongly influenced by the family culture and life course; assumptions of the
Active Aging are more meaningful in the informants' present trajectory. The
content of the narratives pointed to new possibilities of Gerontology Nursing
intervention in Primary Care, aiming at health promotion and intervention,
specially grounded on the respect to the oldest-elders' culture.
PMID- 26422044
TI - Nursing scientific production on health promotion, chronic condition, and aging.
AB - OBJECTIVE: to characterize the scientific production of Postgraduate Programs
Nursing in Brazil on health promotion with a focus on elderly people with chronic
conditions in the period from 2006 to 2010. METHOD: integrative research
developed by searching for dissertations and theses in the database of the Center
for Nursing Studies and Research of the Brazilian Nursing Association published
in the period from 2006 to 2010 and which focused on health promotion for elderly
people with chronic conditions. RESULTS: five themes emerged: "Living with the
disease"; "Technologies of care", "Potential for self-care" "Psycho-spiritual
dimension", and "Family caregiver". CONCLUSION: it was possible to identify
nursing care as a key element to promote the health of elderly people and make
them more independent in their care so as to live with their limitations or
disabilities, even when affected by chronic diseases.
PMID- 26422045
TI - Using the theory of meaningful learning in nursing education.
AB - OBJECTIVE: to synthesize the scientific literature about the Theory of Meaningful
Learning in the process of teaching and learning in nursing. METHOD: this is an
integrative review conducted in the databases MEDLINE, LILACS, SciELO, BDENF and
CINAHL with studies addressing the subject or aspects of the theory of meaningful
learning of David Ausubel. Ten studies were included, from which six were written
in Portuguese and four in English, published from 1998 to 2013. RESULTS: five
studies used the theory of meaningful learning, four studies cited Ausubel as the
author of this theory and only two studies followed the framework for the
application of the theory completely. There are only a few studies on this
subject and those which explore it are not correlated with Ausubel's theory.
CONCLUSION: it is necessary to break with the dichotomy between theory and
practice and promote the articulation of content with action, introducing the
student as the author of their own knowledge.
PMID- 26422046
TI - [Research lines in nursing: phylosophical and epistemological highlights].
AB - In this paper scientific investigation is explained as related to the Nursing
Research Lines and Priorities based on the theory of knowledge application and as
tangible to Subjectivity and Objectivity on what relates to the integrated
categorical terms in the literature as professional, caring and organizational.
OBJECTIVE: to elucidate philosophical and epistemological highlights in the face
of meaningful, essential considerations, in favor of question causalities of
interest to Nursing. METHOD: the reality approach is founded on the theoretical
propositions of Johannes Hessen, with held attention to conceptions of other
recognized authors. RESULTS: one can state the exposition value to clarify
substantive aspects and adjective implications, not only of interest to
investigation, but just to pinpoint the essential meanings on the subject related
to elaborated thesis and dissertations (Marters' and Doctoral). CONCLUSION:
represents a valuable contribution to better clarify details on knowledge
construction and on the subject theme under discussion.
PMID- 26422048
TI - Full-Dimensional Potential Energy Surface and Ro-vibrational Levels of Dioxirane.
AB - A full-dimensional potential energy surface is developed for dioxirane based on a
high-fidelity fit of ~46,000 ab initio points at the CCSD(T)-F12a/AVTZ level. The
ro-vibrational levels of dioxirane were computed using the MULTIMODE method on
this potential energy surface, and the agreement with the available experimental
microwave spectrum is quite satisfactory. In addition, dipole moment surfaces
have been constructed from ab initio data, and they allow the prediction of the
infrared (IR) spectrum.
PMID- 26422050
TI - Effect of Modified Phospholipid Bilayers on the Electrochemical Activity of a
Membrane-Spanning Conjugated Oligoelectrolyte.
AB - The incorporation and electrochemical activity of a conjugated oligoelectrolyte
(COE) in model phospholipid bilayers have been characterized using cyclic
voltammetry and UV-vis absorption measurements. Several other modifiers were also
incorporated into the phospholipid membranes to alter properties such as charge
and alkyl chain disorder. Using potassium ferricyanide to measure charge
transport, it was observed that bilayers that contained cholic acid, a negatively
charged additive that also promotes alkyl chain disorder, had higher COE uptake
and charge permeability than unmodified bilayers. In contrast, when the
positively charged choline was incorporated, charge permeability decreased and
COE uptake was similar to that of unmodified bilayers. The incorporation of
cholesterol at low concentrations within the phospholipid membranes was shown to
enhance the COE's effectiveness at increasing membrane charge permeability
without increasing the COE concentration in the bilayer. Higher concentrations of
cholesterol reduce membrane fluidity and membrane charge permeability.
Collectively, these results demonstrate that changes in phospholipid membrane
charge permeability upon COE incorporation depend not only on the concentration
in the membrane but also on interactions with the phospholipid bilayer and other
additives present in the membranes. This approach of manipulating the properties
of phospholipid membranes to understand COE interactions is applicable to
understanding the behavior of a wide range of molecules that impart useful
properties to phospholipid membranes.
PMID- 26422051
TI - Effects of Exercise Intervention on Habitual Physical Activity Above Lactate
Threshold Under Free-living Conditions: A Randomized Controlled Trial.
AB - The purpose of the present investigation was to examine the effects of an
exercise-based intervention on the daily physical activity (PA) above the lactate
threshold under free-living conditions. A total of 81 middle-aged to older males
(51+/-7 years) were randomly assigned into one of 2 groups. The subjects' body
weight, visceral fat area, lactate threshold (LT), and PA levels were measured
before and after the 8-week lifestyle intervention. The PA levels were assessed
using a pedometer with a uni-axial accelerometer (Lifecorder, Kenz, Nagoya).
During the intervention, 300 min/week of exercise at LT was targeted in the
exercise group. The LT was determined by the log-log transformation method. The
subjects in the control group were instructed to maintain their usual lifestyles.
In the exercise group, the body weight, visceral fat area and LT significantly
improved after the intervention. In contrast, the duration of PA at an intensity
of LT, >3 METs and >6 METs did not differ significantly. The present
investigation did not find significant changes in the PA at LT under free-living
conditions as a result of an 8-week exercise-based intervention, although the
participants successfully improved their aerobic capacity and body composition.
PMID- 26422049
TI - A Social-Ecological View of Barriers and Facilitators for HIV Treatment
Adherence: Interviews with Puerto Rican HIV Patients.
AB - PURPOSE: To identify perceived barriers and facilitators for HAART adherence
among people living with HIV/AIDS in Southern Puerto Rico using a Social
Ecological framework. PATIENTS AND METHODS: Individual in-depths interviews were
conducted with 12 HIV patients with a history of HAART non-adherence. Interviews
were audio-taped and transcribed. Content analysis was performed for each
transcribed interview by three independent coders using a codebook. Using Atlas
TI, super-codes and families were generated to facilitate the categorization tree
as well as grounded analyses and density estimates. RESULTS: Most participants
reported a monthly income of $500 or less (n = 7), a high school education level
(n = 7), being unemployed (n = 9) and being recipients of government health
insurance (n = 11). Three out of six women reported living alone with their
children and most men informed living with their parents or other relatives (n =
4). For the grounded analyses, the top four sub-categories linked to high number
of quotations were mental health barriers (G = 32) followed by treatment regimen
(G = 28), health system (G = 24) and interpersonal relations (G = 16). The top
four sub-categories linked to high number of codes are treatment regimen (D = 4),
health status perception (D = 3), interpersonal relations (D = 3) and health
system (D = 3). CONCLUSION: The results of this study suggest the interconnection
of HIV treatment adherence barriers at various system levels. Future studies on
HIV treatment barriers should explore these interactions and investigate the
possible synergistic effect on non-adherent behavior.
PMID- 26422052
TI - Strength and Pain Threshold Handheld Dynamometry Test Reliability in
Patellofemoral Pain.
AB - Patellofemoral pain syndrome (PFPS), characterized by peri- and retropatellar
pain, is a common disorder in young, active people. The etiology is unclear;
however, quadriceps strength seems to be a contributing factor, and sensitization
might play a role. The study purpose is determining the inter-rater reliability
of handheld dynamometry to test both quadriceps strength and pressure pain
threshold (PPT), a measure for sensitization, in patients with PFPS. This cross
sectional case-control study comprises 3 quadriceps strength and one PPT
measurements performed by 2 independent investigators in 22 PFPS patients and 16
matched controls. Inter-rater reliability was analyzed using intraclass
correlation coefficients (ICC) and Bland-Altman plots. Inter-rater reliability of
quadriceps strength testing was fair to good in PFPS patients (ICC=0.72) and
controls (ICC=0.63). Bland-Altman plots showed an increased difference between
assessors when average quadriceps strength values exceeded 250 N. Inter-rater
reliability of PPT was excellent in patients (ICC=0.79) and fair to good in
controls (ICC=0.52). Handheld dynamometry seems to be a reliable method to test
both quadriceps strength and PPT in PFPS patients. Inter-rater reliability was
higher in PFPS patients compared to control subjects. With regard to quadriceps
testing, a higher variance between assessors occurs when quadriceps strength
increases.
PMID- 26422053
TI - Functional Fatigue Alters Lower-extremity Neuromechanics during a Forward-side
Jump.
AB - Neuromuscular fatigue impairs neuromuscular control of the lower extremity. The
purpose of the study was to investigate the effect of functional fatiguing
exercises on sagittal-plane lower-extremity neuromechanics during a forward-side
jump. 21 participants performed 5 forward-side jump tasks before and after
functional fatiguing exercises. A functional analysis of variance (FANOVA)
evaluated differences between 2 different conditions (pre- vs. post-fatigue) for
joint angle, moment, and EMG amplitude during stance of a forward-side jump.
FANOVA compared variables as polynomial functions, and differences between
functions with 95% confidence interval bands were plotted to determine
significant differences. Plantar, knee, and hip flexion decreased during the
initial stages of landing following fatigue. Plantarflexion moment decreased
during 10-20% of stance in post-fatigue. Knee extension moment initially
increased while decreased during 20-30% of stance following fatigue. Hip
extension moment initially decreased while increased at 20% of stance. Tibialis
anterior EMG decreased during 30-40% of stance, vastus lateralis EMG increased at
15% of stance, hamstring EMG decreased at foot contact and during 25-60% of
stance, and gluteus maximus EMG decreased at foot contact and 35% of stance. The
functional fatiguing exercises resulted in a more upright landing position,
potentially indicating a greater reliance upon skeletal structures for support.
PMID- 26422054
TI - Alterations in Body Fluid Balance During Fin Swimming in 29 degrees C Water in a
Population of Special Forces Divers.
AB - Highly trained "combat swimmers" encounter physiological difficulties when
performing missions in warm water. The aim of this study was to assess the
respective roles of immersion and physical activity in perturbing fluid balance
of military divers on duty in warm water. 12 trained divers performed 2 dives
each (2 h, 3 m depth) in fresh water at 29 degrees C. Divers either remained
Static or swam continuously (Fin) during the dive. In the Fin condition, oxygen
consumption and heart rate were 2-fold greater than during the Static dive. Core
and skin temperatures were also higher (Fin: 38.5+/-0.4 degrees C and 36.2+/-0.3
degrees C and Static: 37.2+/-0.3 degrees C and 34.3+/-0.3 degrees C;
respectively p=0.0002 and p=0.0003). During the Fin dive, the average mass loss
was 989 g (39% urine loss, 41% sweating and 20% insensible water loss and blood
sampling); Static divers lost 720 g (84% urine loss, 2% sweating and 14%
insensible water loss and blood sampling) (p=0.003). In the Fin condition, a
greater decrease in total body mass and greater sweating occurred, without
effects on circulating renin and aldosterone concentrations; diuresis was
reduced, and plasma volume decreased more than in the Static condition.
PMID- 26422055
TI - Running-based Anaerobic Sprint Test as a Procedure to Evaluate Anaerobic Power.
AB - The aim of this study was to evaluate the use of the running anaerobic sprint
test (RAST) as a predictor of anaerobic capacity, compare it to the maximal
accumulated oxygen deficit (MAOD) and to compare the RAST's parameters with the
parameters of 30-s all-out tethered running on a treadmill. 39 (17.0+/-1.4 years)
soccer players participated in this study. The participants underwent an
incremental test, 10 submaximal efforts [50-95% of velocity correspondent to
VO(2MAX) (vVO(2MAX))] and one supramaximal effort at 110% of vVO(2MAX) for the
determination of MAOD. Furthermore, the athletes performed the RAST. In the
second stage the 30-s all-out tethered running was performed on a treadmill (30-s
all-out), and compared with RAST. No significant correlation was observed between
MAOD and RAST parameters. However, significant correlations were found between
the power of the fifth effort (P5) of RAST with peak and mean power of 30-s all
out (r=0.73 and 0.50; p<0.05, respectively). In conclusion, the parameters from
RAST do not have an association with MAOD, suggesting that this method should not
be used to evaluate anaerobic capacity. Although the correlations between RAST
parameters with 30-s all-out do reinforce the RAST as an evaluation method of
anaerobic metabolism, such as anaerobic power.
PMID- 26422056
TI - The Power of Advanced Capability and Informed Policy.
PMID- 26422057
TI - Excited Biexcitons in Transition Metal Dichalcogenides.
AB - The Stochastic Variational Method (SVM) is used to show that the effective mass
model correctly estimates the binding energies of excitons and trions but fails
to predict the experimental binding energy of the biexciton. Using high-accuracy
variational calculations, it is demonstrated that the biexciton binding energy in
transition metal dichalcogenides is smaller than the trion binding energy,
contradicting experimental findings. It is also shown that the biexciton has
bound excited states and that the binding energy of the L = 0 excited state is in
very good agreement with experimental data. This excited state corresponds to a
hole attached to a negative trion and may be a possible resolution of the
discrepancy between theory and experiment.
PMID- 26422058
TI - Pain grade and sleep disturbance in older adults: evaluation the role of pain,
and stress for depressed and non-depressed individuals.
AB - OBJECTIVE: The aim of this paper was to assess the relationship between pain and
sleep in older adults taking depression, stress, and medical comorbidities into
account. METHODS: A cross-sectional analysis was performed using Einstein Aging
Study, a community-based cohort study of adults aged 70 years and older. Ratings
of pain intensity and interference from the Medical Outcomes Study (MOS) Short
Form 36 were used to assign individuals to low-pain versus high-pain severity.
Sleep disturbance was assessed using the nine-item sleep problems index from the
Medical Outcomes Study Sleep Scale. Other measures included the Geriatric
Depression Scale and Perceived Stress Scale (PSS). Linear regression models were
used to assess the association between pain grade and sleep disturbance adjusted
for demographics, PSS, Geriatric Depression Scale, and other comorbidities.
RESULTS: Five hundred sixty-two eligible participants with a mean age of 78.22
years (standard deviation = 5.43) were included; 64% were women. Pain grade [beta
= 5.40, 95% confidence interval (CI) 2.56-8.21, p < 0.001] was associated with
sleep disturbance after adjusting for demographic variables. In models including
pain grade (beta = 3.08, 95% CI 0.32-5.85, p = 0.03) and PSS (beta = 0.57, 95% CI
0.39-0.75, p < 0.001), both were associated with sleep disturbance, although the
PSS attenuated the relationship between pain and sleep by 34%. Depression, when
added to previous model, was also associated with sleep (beta = 2.17, 95% CI 1.48
2.85, p < 0.001) and attenuated the relationship between pain (beta = 2.41, 95%
CI -0.25 to 5.08, p = 0.07) and sleep by 22%. Stratified for depression, we found
that pain, stress, and other medical comorbidities were significantly associated
with sleep disturbance in non-depressed individuals but not individuals with
depression. CONCLUSIONS: Pain, stress, and medical comorbidities are associated
with sleep disturbance, especially in non-depressed older adults.
PMID- 26422059
TI - Material identification in x-ray microscopy and micro CT using multi-layer, multi
color scintillation detectors.
AB - We demonstrate that a dual-layer, dual-color scintillator construct for
microscopic CT, originally proposed to increase sensitivity in synchrotron
imaging, can also be used to perform material quantification and classification
when coupled with polychromatic illumination. We consider two different
approaches to data handling: (1) a data-domain material decomposition whose
estimation performance can be characterized by the Cramer-Rao lower bound
formalism but which requires careful calibration and (2) an image-domain material
classification approach that is more robust to calibration errors. The data
domain analysis indicates that useful levels of SNR (>5) could be achieved in one
second or less at typical bending magnet fluxes for relatively large amounts of
contrast (several mm path length, such as in a fluid flow experiment) and at
typical undulator fluxes for small amount of contrast (tens of microns path
length, such as an angiography experiment). The tools introduced could of course
be used to study and optimize parameters for a wider range of potential
applications. The image domain approach was analyzed in terms of its ability to
distinguish different elemental stains by characterizing the angle between the
lines traced out in a two-dimensional space of effective attenuation coefficient
in the front and back layer images. This approach was implemented at a
synchrotron and the results were consistent with simulation predictions.
PMID- 26422060
TI - Distribution of trace elements in sediment and soil from river Vardar Basin,
Macedonia/Greece.
AB - A systematic study was carried out to investigate the distribution of 59 elements
in the sediment and soil samples collected from the river Vardar (Republic of
Macedonia and Greece) and its major tributaries. The samples were collected from
28 sampling sites. Analyses were performed by inductively coupled plasma-mass
spectrometry. R-mode factor analysis (FA) was used to identify and characterise
element associations. Seven associations of elements were determined by the
method of multivariate statistics. Every factor (Factors 1-3 and 6 and 7 as
geogenic and Factors 4 and 5 as anthropogenic associations of elements) are
examined and explained separately. The distribution of various elements showed
that there is a presence of anthropogenic elements (Ag, Cd, Cu, Ge, Pb, Sn and
Zn) introduced in the river sediments and soils from the mining, metallurgical,
industrial and agricultural activities in Vardar River Basin, which covers most
of the Republic of Macedonia and Central-northern part of Greece.
PMID- 26422061
TI - Zinc Isotope Variability in Three Coal-Fired Power Plants: A Predictive Model for
Determining Isotopic Fractionation during Combustion.
AB - The zinc (Zn) isotope compositions of feed materials and combustion byproducts
were investigated in three different coal-fired power plants, and the results
were used to develop a generalized model that can account for Zn isotopic
fractionation during coal combustion. The isotope signatures in the coal
(delta(66)ZnIRMM) ranged between +0.73 and +1.180/00, values that fall well
within those previously determined for peat (+0.6 +/-2.00/00). We therefore
propose that the speciation of Zn in peat determines the isotope fingerprint in
coal. All of the bottom ashes collected in these power plants were isotopically
depleted in the heavy isotopes relative to the coals, with delta(66)ZnIRMM values
ranging between +0.260/00 and +0.640/00. This suggests that the heavy isotopes,
possibly associated with the organic matter of the coal, may be preferentially
released into the vapor phase. The fly ash in all of these power plants was, in
contrast, enriched in the heavy isotopes relative to coal. The signatures in the
fly ash can be accounted for using a simple unidirectional fractionation model
with isotope fractionation factors (alphasolid-vapor) ranging between 1.0003 and
1.0007, and we suggest that condensation is the controlling process. The model
proposed allows, once the isotope composition of the feed coal is known, the
constraining of the Zn signatures in the byproducts. This will now enable the
integration of Zn isotopes as a quantitative tool for the source apportionment of
this metal from coal combustion in the atmosphere.
PMID- 26422062
TI - Growth of Cu2ZnSnS4 Nanocrystallites on TiO2 Nanorod Arrays as Novel Extremely
Thin Absorber Solar Cell Structure via the Successive-Ion-Layer-Adsorption
Reaction Method.
AB - Cu2ZnSnS4 (CZTS) is an environmentally benign semiconductor with excellent
optoelectronic properties that attracts a lot of interest in thin film
photovoltaics. In departure from that conventional configuration, we fabricate
and test a novel absorber-conductor structure featuring in situ successive-ion
layer-adsorption-reaction (SILAR)-deposited CZTS nanocrystallites as a light
absorber on one-dimensional TiO2 (rutile) nanorods as an electron conductor. The
effectiveness of the nanoscale heterostructure in visible light harvesting and
photoelectron generation is demonstrated with an initial short circuit current
density of 3.22 mA/cm(2) and an internal quantum efficiency of ~60% at the blue
light region, revealing great potential in developing CZTS extremely thin
absorber (ETA) solar cells.
PMID- 26422063
TI - [Lengthening temporalis myoplasty: Technical refinements].
AB - First described by Labbe in 1997, the lengthening temporalis myoplasty (LTM)
ensures the transfer of the entire temporal muscle from the coronoid process to
the upper half of the lip without interposition of aponeurotic tissue. Thanks to
brain plasticity, the temporal muscle is able to change its function because it
is entirely mobilized towards another effector: the labial commissure. After 6
months of speech rehabilitation, the muscle loses its chewing function and it
acquires its new smiling function. We describe as far as possible all the
technical points to guide surgeons who would like to perform this powerful
surgical procedure. We show the coronoid process approaches both through an upper
temporal fossa approach and a lower nasolabial fold approach. Rehabilitation
starts 3 weeks after the surgery following a standardized protocol to move from a
mandibular smile to a voluntary smile, and then a spontaneous smile in 3 steps.
The LTM is the main part of a one-stage global treatment of the paralyzed face.
It constitutes a dynamic palliative treatment usually started at the sequelae
stage, 18 months after the outcome of a peripheral facial paralysis. This one
stage procedure is a reproducible and relevant surgical technique in the
difficult treatment of peripheral facial paralysis. An active muscle is
transferred to reanimate the labial commissure and to recreate a mobile
nasolabial fold.
PMID- 26422065
TI - Synthesis of tin oxide nanospheres under ambient conditions and their strong
adsorption of As(III) from water.
AB - The development of highly efficient As(iii) adsorbents is critical to largely
simplify the arsenic treatment process and lower its cost. For the first time,
SnO2 nanospheres were demonstrated to possess a highly efficient As(iii)
adsorption capability from water in a near neutral pH environment as predicted by
the material criterion we recently developed for the selection of highly
efficient arsenic adsorbents. These SnO2 nanospheres were synthesized by a simple
and cost-effective hydrolysis process with the assistance of ethyl acetate under
ambient conditions, which had a good dispersity, a narrow size distribution, a
relatively large specific surface area, and a porous structure. A fast As(iii)
adsorption was observed in the kinetics study on these SnO2 nanospheres, and
their Langmuir adsorption capacity was determined to be ~112.7 mg g(-1) at pH ~7.
The As(iii) adsorption mechanism on SnO2 nanospheres was examined by both
macroscopic and microscopic techniques, which demonstrated that it followed the
inner-sphere complex model. These SnO2 nanospheres demonstrated effective As(iii)
adsorption even with exceptionally high concentrations of co-existing ions, and a
good regeneration capability by washing with NaOH solution.
PMID- 26422064
TI - Cultural differences and shame in an expressive writing alcohol intervention.
AB - The present study evaluates the relationships between shame, culture, and
drinking behavior in predicting drinking intentions in the context of an
expressive writing intervention. Theory and empirical findings have generally
found that shame is maladaptive and can lead to anxiety, depression, and
problematic alcohol use. However, research on cultural differences suggests that
shame may be differentially damaging to individuals of collectivist, Asian
cultures. Previous research evaluating expressive writing as a brief alcohol
intervention has shown promising results such as reduced drinking intentions and
increased readiness to change drinking behavior. The present study tested the
hypothesis that feelings of shame after writing about a negative heavy drinking
event would be associated with greater alcohol use generally and that this effect
would differ for Caucasian compared to Asian individuals. We also explored
whether this differed for light and heavy drinkers. Two hundred sixty-four
undergraduates (74% female) who drank at least one alcoholic beverage in the past
month completed measures of demographics, baseline drinking, event-related shame
and guilt, pre- and postwriting affect, and drinking intentions. Results revealed
that, independent of affect, social desirability, and event-related guilt, shame
was generally negatively associated with drinking intentions for Caucasians and
light drinking Asians. However, for heavy drinking Asians, shame was associated
with increased drinking intentions. Results suggest that interventions that
elicit shame are differentially effective and should be targeted accordingly.
PMID- 26422066
TI - A Versatile Cell Death Screening Assay Using Dye-Stained Cells and Multivariate
Image Analysis.
AB - A novel dye-based method for measuring cell death in image-based screens is
presented. Unlike conventional high- and medium-throughput cell death assays that
measure only one form of cell death accurately, using multivariate analysis of
micrographs of cells stained with the inexpensive mix, red dye nonyl acridine
orange, and a nuclear stain, it was possible to quantify cell death induced by a
variety of different agonists even without a positive control. Surprisingly,
using a single known cytotoxic agent as a positive control for training a
multivariate classifier allowed accurate quantification of cytotoxicity for
mechanistically unrelated compounds enabling generation of dose-response curves.
Comparison with low throughput biochemical methods suggested that cell death was
accurately distinguished from cell stress induced by low concentrations of the
bioactive compounds Tunicamycin and Brefeldin A. High-throughput image-based
format analyses of more than 300 kinase inhibitors correctly identified 11 as
cytotoxic with only 1 false positive. The simplicity and robustness of this dye
based assay makes it particularly suited to live cell screening for toxic
compounds.
PMID- 26422067
TI - [General practitioners are the first to observe psychoses].
PMID- 26422068
TI - [Psychotherapy: sitting or reclining?].
PMID- 26422069
TI - [CME. Patient advance directives in family medicine].
PMID- 26422071
TI - [Endocrine causes of delirium].
AB - Delirium is common in hospitalized patients and apart from well known vascular,
infectious and toxic causes there are many endocrine diseases which may also
present as an acute confusional state. The review provides an overview of the
different endocrine etiologies of delirium and the prompt diagnosis and
treatment.
PMID- 26422072
TI - [Psychotic disorders: special aspects in general practice].
AB - In emergency situations the general practitioner is often the first professional
contact psychotic patients have. The following article conveys basic knowledge
about psychotic disorders and their clinical features typically seen in general
practice.
PMID- 26422074
TI - Pyogenic Hepatic Abscess--Less is More. A Review for General Internists.
AB - Pyogenic hepatic abscesses are rare, and fatal if untreated. Recent progresses in
diagnostic and interventional radiology facilitated their management. However,
abscesses located in the caudate lobe are still a diagnostic and therapeutic
challenge, especially to general internists, who tend to overtreatment.
Literature of this specific form of hepatic abscess is scarce. The aim of this
article was to review the existing literature on caudate lobe abscesses, as well
as to provide a brief overview over pyogenic liver abscesses in order to draw
attention of general internists to this important differential diagnosis and
facilitate the decision-making on therapy. We underline that current evidence
suggests a less is more position, so as to warrant a quality approach.
PMID- 26422073
TI - [How healthy are and behave men? Differences in health status and health behavior
between the two sexes in the Canton of Zurich].
AB - Men have not been the focus of health monitoring and reporting in German-speaking
Switzerland so far and are a largely neglected target group of governmental
preventive efforts. Without good reason. Men have a substantial preventive
potential regarding health, health behavior and use of health and medical
services, as can be seen in the recently published global health report of the
Canton Zurich. Men have a shorter life expectancy compared to women and a
significantly higher mortality with regard to strongly behavior-related chronic
diseases as well as fatal traffic accidents and suicides. Men also show
comparably unfavourable health behavior and a reduced utilization of health
services. The stronger, but also less healthy and less healthy behaving sex
should increasingly be the focus of health reporting and health monitoring in the
future.
PMID- 26422075
TI - [Mass on the neck].
AB - Malignant peripheral nerve sheath tumors (MPNST) are rare. But especially in
patients with known neurofibromatosis type 1 (von Recklinghausen), this entity of
tumors should not be forgotten. The indication for open biopsy or excision should
be made generously. In the following, we report a rare case of MPNST, which
highlights the importance of rapid diagnosis and treatment.
PMID- 26422076
TI - [Liraglutide for weight loss in overweight and obese adults].
PMID- 26422077
TI - [Cannabinoids in medical procedures - Review and Meta-analysis].
PMID- 26422082
TI - Primary autoimmune myelofibrosis as etiology of pancytopenia mimicking
myelodysplastic syndrome.
PMID- 26422081
TI - Living in biological soil crust communities of African deserts-Physiological
traits of green algal Klebsormidium species (Streptophyta) to cope with
desiccation, light and temperature gradients.
AB - Green algae of the genus Klebsormidium (Klebsormidiales, Streptophyta) are
typical members of biological soil crusts (BSCs) worldwide. The phylogeny and
ecophysiology of Klebsormidium has been intensively studied in recent years, and
a new lineage called superclade G, which was isolated from BSCs in arid southern
Africa and comprising undescribed species, was reported. Three different African
strains, that have previously been isolated from hot-desert BSCs and molecular
taxonomically characterized, were comparatively investigated. In addition,
Klebsormidium subtilissimum from a cold-desert habitat (Alaska, USA, superclade
E) was included in the study as well. Photosynthetic performance was measured
under different controlled abiotic conditions, including dehydration and
rehydration, as well as under a light and temperature gradient. All Klebsormidium
strains exhibited optimum photosynthetic oxygen production at low photon fluence
rates, but with no indication of photoinhibition under high light conditions
pointing to flexible acclimation mechanisms of the photosynthetic apparatus.
Respiration under lower temperatures was generally much less effective than
photosynthesis, while the opposite was true for higher temperatures. The
Klebsormidium strains tested showed a decrease and inhibition of the effective
quantum yield during desiccation, however with different kinetics. While the
single celled and small filamentous strains exhibited relatively fast inhibition,
the uniserate filament forming isolates desiccated slower. Except one, all other
strains fully recovered effective quantum yield after rehydration. The presented
data provide an explanation for the regular occurrence of Klebsormidium strains
or species in hot and cold deserts, which are characterized by low water
availability and other stressful conditions.
PMID- 26422083
TI - Donor-specific HLA alloantibodies: Impact on cardiac allograft vasculopathy,
rejection, and survival after pediatric heart transplantation.
AB - BACKGROUND: There is increasing evidence that donor-specific anti-HLA antibodies
(DSA) are associated with poor outcomes after cardiac transplantation in adults,
but data are limited in children. The objective of this study was to examine the
development and consequences of de novo DSA in pediatric recipients of heart
transplants. METHODS: We analyzed 105 pediatric patients who received heart
transplants at our center from January 2002 to December 2012. All patients had
negative T-cell and B-cell post-transplant crossmatches. Patients underwent HLA
antibody screening at 1, 2, 3, 6, and 12 months post-transplant and annually
thereafter unless there was suspicion for rejection. HLA class I and II
antibodies were identified using Luminex assay. Coronary angiography was
performed at 1 year and annually thereafter. Acute cellular rejection, antibody
mediated rejection, and treated clinical rejections were included together as
rejection events. RESULTS: Of 105 patients, 45 (43%) developed de novo DSA. DSA
positive patients had significantly higher rates of coronary artery vasculopathy
(CAV) compared with DSA-negative patients (36% vs 13%). CAV-free survival at 1
year and 5 years post-transplant for DSA-negative patients was 90% and 25%,
respectively, compared with 70% and 0%, respectively, for DSA-positive patients
(p < 0.01). DSA-positive patients had 2.5 times more rejection events per year
than DSA-negative patients. The 5-year graft survival rate was 72.4% for DSA
negative patients and 21% for DSA-positive patients (p < 0.001). CONCLUSIONS: De
novo DSA has a strong negative impact on CAV, rejection, and graft survival in
pediatric recipients of heart transplants.
PMID- 26422084
TI - The Effectiveness of Interventions for Improving the Research Literacy of Nurses:
A Systematic Review.
AB - BACKGROUND: Internationally, a considerable body of research exists examining why
nurses do not use evidence in practice. Consistently, the research finds that
lack of knowledge about research or discomfort with understanding research
terminology are among the chief reasons given. Research education is commonly
included in undergraduate nursing degree programs, but this does not seem to
translate into a strong understanding of research following graduation, or an
ability to use it in practice. AIM: The objective of this review was to identify
the effectiveness of workplace, tertiary-level educational, or other
interventions designed to improve or increase postregistration nurses'
understanding of research literature and ability to critically interact with
research literature with the aim of promoting the use of research evidence in
practice in comparison to no intervention, other intervention, or usual practice.
METHODS: A wide range of databases were searched for quantitative studies of
registered nurses receiving educational interventions designed to increase or
improve their understanding of research literature in tertiary or workplace
settings. Two reviewers working independently critically appraised the relevant
papers and extracted the data using Joanna Briggs Institute instruments. Data are
presented as a narrative summary as no meta-analysis was possible. RESULTS:
Searching identified 4,545 potentially relevant papers, and after the sifting of
titles and abstracts, 96 papers were selected for retrieval. On examination of
full-text versions, 10 of the 96 retrieved papers were found to meet the
inclusion criteria. Included studies were low to moderate quality. Interactive or
activity-based learning seems to be effective in terms of improving research
knowledge, critical appraisal ability, and research self-efficacy. Utilizing a
program with a strong base in an appropriate theory also seems to be associated
with greater effectiveness, particularly for workplace interventions. LINKING
EVIDENCE TO ACTION: The included studies strongly favored interactive
interventions, and those utilizing theory in their construction. Therefore, these
types of interventions should be implemented to improve the effectiveness of
research education for nurses as well as their research literacy.
PMID- 26422085
TI - Diagnosis of pulmonary and extrapulmonary tuberculosis based on detection of
mycobacterial antigen 85B by immuno-PCR.
AB - We developed a novel indirect sandwich immuno-polymerase chain reaction (I-PCR)
assay for the detection of mycobacterial antigen 85B (Ag85B, 30kDa, Rv1886c) in
pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) patients. The
amino-modified reporter DNA was covalently attached with the antidetection
antibody through a heterobifunctional cross-linking agent succinimidyl 4-[N
maleimidomethyl]-cyclohexane-1-carboxylate. The detection limit of Ag85B by I-PCR
was found to be 1 femtogram (fg)/mL, which was 10(6)-fold lower than an analogous
enzyme-linked immunosorbent assay (ELISA). The sensitivities of 85% and 77% with
I-PCR and 77.6% and 62.5% with ELISA were observed in smear-positive and smear
negative PTB patients, respectively, with high specificity. On the other hand,
sensitivities of 84% and 63.7% with I-PCR and 68% and 47.5% with ELISA were
observed in confirmed and clinically suspected EPTB cases, respectively, with
high specificity.
PMID- 26422086
TI - Bacteremia caused by a mecA-positive oxacillin-susceptible Staphylococcus aureus
strain with inducible resistance.
PMID- 26422087
TI - Outcomes of Prolonged Laparoscopic Bariatric Operations Compared With Shorter
Open Procedures.
AB - PURPOSE: Prolonged operative time (ORT) is a drawback of laparoscopic bariatric
surgery due to concerns for increased morbidity. This study aims to identify the
ORT when open procedures are superior to laparoscopic procedures. METHODS: Thirty
day outcomes for bariatric procedures in the NSQIP database were analyzed
comparing laparoscopic ORT to equal or shorter open ORT. Multivariate regression
was utilized to control for patient demographics and comorbidities. RESULTS:
Among 48,274 cases, laparoscopic procedures reduced morbidity and mortality
compared with open procedures of similar ORT. Laparoscopic procedures <=3 hours
were equal or superior to shorter open procedures. Laparoscopic procedures >6
hours had worse outcomes than open operations <3 hours. Open operations >3 hours
had no benefit regardless of ORT. CONCLUSIONS: Laparoscopic bariatric operations
have less mortality and morbidity compared with open procedures of similar ORT.
The advantages of laparoscopic procedures are eliminated when ORT exceeds 6 hours
compared with shorter open procedures.
PMID- 26422088
TI - Postoperative Pain After Robotic Thyroidectomy by a Gasless Unilateral Axillo
Breast or Axillary Approach.
AB - The aim of this study was to compare postoperative pain after robotic
thyroidectomy with that after conventional open thyroidectomy. We analyzed 123
patients who underwent robotic thyroidectomy and 170 patients who underwent
conventional open thyroidectomy. Postoperative pain was evaluated on a visual
analogue scale rating of 0 to 10, 1 day to 1 month after surgery. Mean pain
visual analogue scale scores for the robotic and open groups were 3.33 and 3.57
(P=0.476) on day 1, 2.29 and 2.58 (P=0.285) on day 3, 2.19 and 1.74 (P=0.057)
after 1 week, and 0.98 and 1.01 (P=0.843) after 1 month, respectively. There was
no difference between the 2 groups in the doses of parenteral analgesic
medication administered (robotic vs. open, mean 174 vs. 194 mg, P=0.189). In
conclusion, postoperative pain and the dose of analgesic medication in both
groups are similar.
PMID- 26422089
TI - Laparoscopic Splenectomy in Patients With Spleen Injuries.
AB - INTRODUCTION: Spleen injury appears in 10% to 30% of abdominal trauma patients.
Mortality among the patients in the last 20 years remains high (6% to 7%) and
shows no tendency to decline. Nowadays nonoperative management is widely accepted
management of patients with low-grade spleen injury, whereas management of
patients with high-grade spleen injury (III and higher) is not so obvious. There
are 3 methods exist in treatment of such patients: conservative (with or without
angioembolization), spleen-preserving operations, and splenectomy. Today
laparoscopic splenectomy is not a widely used operation and only few studies
reported about successful use of laparoscopic splenectomy in patients with spleen
injury.The aim of the study was to determine indications and contraindications
for laparoscopic splenectomy in abdominal trauma patients and to analyze results
of the operations. PATIENTS AND METHODS: The study involved 42 patients with
spleen injury grade III who were admitted in our institute in the years of 2010
to 2014. The patients were divided in 2 groups. Laparoscopic splenectomy was
performed in 23 patients (group I) and "traditional" splenectomy was carried out
in 19 patients (group II). There was no difference in the demographic data and
trauma severity between the 2 groups. Noninvasive investigations, such as
laboratory investigations, serial abdominal ultrasound examinations, x-ray in
multiple views, and computed tomography had been performed before the decision
about necessity of an operation was made. RESULTS: Patients after laparoscopic
operations had better recovering conditions compared with patients with the same
injury after "traditional" splenectomy. Neither surgery-related complications nor
mortalities were registered in both groups. Laparoscopic splenectomy was more
time-consuming operation than "traditional" splenectomy. We suggest that as
experience of laparoscopic splenectomy is gained the operation time will be
reduced. CONCLUSIONS: Laparoscopic splenectomy is a safe feasible operation in
patients with spleen injury. The operation is indicated in patients with spleen
laceration >3 cm of parenchymal depth with moderate continuing bleeding or
expanding hematoma and contraindicated in patients with hemodynamic instability
and high bleeding rate (>500 mL/h on serial ultrasound examinations).
PMID- 26422090
TI - Infectious disease, injection practices, and risky sexual behavior among anabolic
steroid users.
AB - Anabolic-androgenic steroids (AAS) and other performance-enhancing drugs (PEDs)
are commonly misused to increase muscle size and strength, as well as improve
physical appearance. Many AAS and certain PEDs are administered via injection and
therefore pose a risk for transmission of infectious diseases such as human
immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV),
and skin and soft tissue infections (SSTIs). Further, AAS users may be more
likely to take part in high-risk sexual behaviors than non-AAS users. This review
explores the prevalence of infectious diseases as well as risky injection
practices and sexual behaviors of AAS users in the current literature. A
comprehensive MEDLINE search (1984-17 April 2015) for English language reports
was performed on AAS users. Ten studies analyzed the prevalence of HIV infection,
6 studies analyzed HBV infection, and 6 studies analyzed HCV infection; 20
studies analyzed injection practices and 7 studies analyzed high-risk sexual
behaviors of AAS users. HIV, HBV, HCV, and SSTIs have been associated with AAS
users. In particular, HIV infection seems much higher among homosexual male AAS
users. AAS users also take part in high-risk injection practices but to a much
lower extent than intravenous drug users. AAS users are also more likely to
engage in high-risk sexual behaviors than the general population. Clinicians and
health-policy leaders may utilize these findings to implement strategies to
decrease the spread of infectious diseases.
PMID- 26422091
TI - X-linked moyamoya syndrome associated with severe haemophilia A.
PMID- 26422092
TI - Introduction.
PMID- 26422093
TI - Safety and Tolerability of Esomeprazole in Children With Gastroesophageal Reflux
Disease.
AB - OBJECTIVES: To evaluate safety, tolerability, and symptom improvement with once
daily esomeprazole in children with endoscopically proven gastroesophageal reflux
disease (GERD). PATIENTS AND METHODS: In this 8-week, multicenter, randomized,
uncontrolled, double-blind study, children ages 1 to 11 years were stratified by
weight to receive esomeprazole 5 or 10 mg (children < 20 kg) or 10 or 20 mg
(children >= 20 kg) once daily. Safety and tolerability was assessed by
evaluating adverse events (AEs; both treatment- and non-treatment-related AEs)
and changes from baseline in medical history, physical examinations, and clinical
laboratory tests. Investigators scored symptom severity every 2 weeks using the
Physician's Global Assessment (PGA). Patients' parents rated GERD symptoms of
heartburn, acid regurgitation, and epigastric pain (none to severe, 0-3) at
baseline (based on past 72 hours) and daily (from past 24 hours). RESULTS: Of 109
patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2%
of children <20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9%
and 82.8% of children >= 20 kg receiving esomeprazole 10 and 20 mg, respectively,
regardless of causality. Overall, only 9.3% of patients reported 13 treatment
related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9%
[2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients,
was not judged by the investigator to be related to treatment. At the final
visit, PGA scores improved significantly from baseline (P < 0.001). Of 58
patients with moderate to severe baseline PGA symptom scores, 91.4% had lower
scores by the final visit. GERD symptom scores were significantly improved from
baseline to the final week of the study in all of the treatment groups (P < 0.01)
CONCLUSIONS:: In children ages 1 to 11 years with endoscopically proven GERD,
esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated.
The frequency and severity of GERD-related symptoms were significantly reduced
during the active treatment period.
PMID- 26422094
TI - Pharmacokinetics and Acid-suppressive Effects of Esomeprazole in Infants 1-24
Months Old With Symptoms of Gastroesophageal Reflux Disease.
AB - OBJECTIVES: To evaluate the pharmacokinetics and acid-suppressive effects of
esomeprazole in infants with gastroesophageal reflux disease (GERD). PATIENTS AND
METHODS: In this single-blind, randomized, parallel-group study, 50 infants 1 to
24 months old with symptoms of GERD, and >= 5% of time with intraesophageal pH <4
during 24-hour dual pH monitoring, received oral esomeprazole 0.25 mg/kg (n = 26)
or 1 mg/kg (n = 24) once daily for 1 week. Intraesophageal and intragastric pH
were recorded at 1 week, and blood samples were taken for pharmacokinetic
analysis. RESULTS: At baseline, mean percentages of time with intragastric pH >4
and intraesophageal pH <4 were 30.5% and 11.6%, respectively, in the esomeprazole
0.25 mg/kg group and 28.6% and 12.5% in the esomeprazole 1 mg/kg group. After 1
week of treatment, times with intragastric pH >4 were 47.9% and 69.3% in the
esomeprazole 0.25 mg/kg and 1 mg/kg groups, respectively (P < 0.001 vs baseline),
and times with intraesophageal pH <4 were 8.4% (P < 0.05 vs baseline) and 5.5% (P
< 0.001 vs. baseline), respectively. The mean number of acid reflux episodes of
>5 minutes duration decreased from 6 at baseline to 3 and 2 with esomeprazole
0.25 mg/kg and 1 mg/kg, respectively. The geometric mean AUC0-t of esomeprazole
were 0.24 and 1.79 MUmol . h/L for the 0.25 mg/kg and 1 mg/kg dosages of
esomeprazole, respectively. Both esomeprazole dosages were well tolerated.
CONCLUSIONS: Oral treatment with esomeprazole 0.25 mg/kg and 1 mg/kg was well
tolerated and provided dose-related acid suppression, dose-related exposure to
esomeprazole, and decreased esophageal acid exposure in infants 1-24 months old
with GERD.
PMID- 26422095
TI - Esomeprazole for the Treatment of Erosive Esophagitis in Children: An
International, Multicenter, Randomized, Parallel-Group, Double-Blind (for Dose)
Study.
AB - BACKGROUND: Acid suppression with a proton pump inhibitor is standard treatment
for gastroesophageal reflux disease and erosive esophagitis in adults and
increasingly is becoming first-line therapy for children aged 1-17 years. We
evaluated endoscopic healing of erosive esophagitis with esomeprazole in young
children with gastroesophageal reflux disease and described esophageal histology.
METHODS: Children aged 1-11 years with endoscopically or histologically confirmed
gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily
(<20 kg) or 10 or 20 mg daily (>= 20 kg) for 8 weeks. Patients with erosive
esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions.
RESULTS: Of 109 patients, 49% had erosive esophagitis and 51% had histologic
evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients
who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced
erosion resolution. Dilation of intercellular space was reported in 24% of
patients with histologic examination. CONCLUSIONS: Esomeprazole (0.2-1.0 mg/kg)
effectively heals macroscopic and microscopic erosive esophagitis in this
pediatric population with gastroesophageal reflux disease. Dilation of
intercellular space may be an important histologic marker of erosive esophagitis
in children.
PMID- 26422096
TI - Healing of Erosive Esophagitis and Improvement of Symptoms of Gastroesophageal
Reflux Disease After Esomeprazole Treatment in Children 12 to 36 Months Old.
AB - OBJECTIVES: The aim of the study was to evaluate erosive esophagitis healing and
symptom improvement with once-daily esomeprazole in children ages 12 to 36 months
with endoscopically or histologically proven gastroesophageal reflux disease
(GERD). PATIENTS AND METHODS: Data from children ages 12 to 36 months were
included in a post-hoc analysis of an 8-week, multicenter, randomized, and double
blind by dose strata study of patients ages 1 to 11 years with endoscopically or
histologically confirmed GERD. Children were randomized to receive esomeprazole 5
or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal
biopsy at baseline. Patients who had erosive esophagitis (graded using the Los
Angeles classification system) at baseline underwent a follow-up endoscopy at
final study visit to assess healing of erosive esophagitis. Investigators scored
severity of GERD symptoms at baseline and every 2 weeks using the Physician
Global Assessment. RESULTS: Thirty-one of 109 primary study patients ages 12 to
36 months were included in the post hoc analysis. At baseline, 15 patients
(48.4%) had erosive esophagitis, underwent follow-up endoscopy, and were healed
after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate-to
severe baseline Physician Global Assessment symptom scores, 84.2% had lower
scores by the final visit. Following esomeprazole treatment, GERD symptoms were
significantly improved from baseline to final visit (P <= 0.0018). CONCLUSIONS:
Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and
symptoms of GERD in children as young as 1 year.Moreover, although not yet
validated in pediatric patients, the Los Angeles classification system was useful
in grading erosive esophagitis in children ages 12 to 36 months.
PMID- 26422097
TI - Esomeprazole for the Treatment of GERD in Infants Ages 1-11 Months.
AB - OBJECTIVES: Gastroesophageal reflux disease (GERD) is present in pediatric
patients when reflux of gastric contents causes troublesome symptoms and/ or
complications. The present study evaluates the efficacy and safety of
esomeprazole in infants ages 1 to 11 months with GERD. METHODS: In this
multicenter randomized, double-blind, placebo-controlled, parallel-group,
treatment-withdrawal study, infants received open-label, weight-adjusted doses of
esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement
were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo
for 4 weeks. The primary endpoint was time to discontinuation owing to symptom
worsening based on global assessments by the parent/guardian and physician.
Adverse events were recorded. RESULTS: Of the 98 patients enrolled, 81 (82.7%)
experienced symptom improvement determined by physician global assessment (PGA)
during open-label esomeprazole treatment; 80 entered the double-blind phase.
During this phase, discontinuation rates owing to symptom worsening were 48.8%
(20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated
patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with
symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to
discontinuation was significantly longer with esomeprazole than placebo (hazard
ratio 0.24; P = 0.01); the complementary subgroup difference was not significant
(hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS: The
discontinuation rate owing to symptom worsening did not differ significantly
between infants receiving esomeprazole versus those receiving placebo. Improved
diagnostic criteria in this age group are needed to identify infants with GERD
who may benefit from acid suppression therapy.
PMID- 26422098
TI - Has Afirma gene expression classifier testing refined the indeterminate thyroid
category in cytology?
AB - BACKGROUND: Thyroid fine-needle aspiration (FNA) plays a pivotal role in the
evaluation of thyroid nodules. Up to 30% of cases are diagnosed as indeterminate
by FNA, including atypia of undetermined significance, follicular lesion of
undetermined significance, suspicious for a follicular neoplasm, and follicular
neoplasm, with approximately two-thirds having a benign outcome. The gene
expression classifier (GEC) test is a molecular test for cases with indeterminate
cytology. The purpose of the current study was to examine the refining role of
the GEC test within a single institution. METHODS: Retrospective analysis of all
thyroid FNAs during a 20-month period after implementation of GEC was performed.
Cases of indeterminate cytology with concomitant GEC testing were selected and
divided further in 4 subgroups. Correlation with surgical follow-up, when
available, was performed. The results were compared with previously published
data from the study institution before the implementation of GEC testing.
RESULTS: Among the 217 cases, there were 189 with indeterminate cytology, 42% of
which were benign and 50% of which were suspicious by GEC. The excisional rate of
atypia of undetermined significance-follicular lesion of undetermined
significance in the pre-GEC category was 63%, which decreased to 35% in the post
GEC category, whereas the malignancy rate in the excised thyroids increased from
35% in the pre-GEC category to 47% in the post-GEC category. Similar findings
also were obtained for suspicious for a follicular neoplasm-follicular neoplasm
lesions. CONCLUSIONS: The strength of the GEC test appears to lie in its ability
to reclassify 42% of indeterminate cytology cases as benign, thereby decreasing
the number of unnecessary surgical procedures.
PMID- 26422099
TI - Hormonal impact on tumor growth and progression.
AB - In this review, current knowledge of hormones impact on prostate, breast and
endometrium cancer growth and transition to hormone therapy resistant phenotype
is summarized. A special consideration is given to genetic alterations and
hormone responsive signa-ling pathways. Estrogen, androgen and progesterone are
the key drivers in these cancer variants. Hormone receptors and their interplay
with plenty of growth factors generated by the tumor microenvironment contribute
greatly to carcinogenesis and cancer cell proliferation. The tumor cell
plasticity that could explain a loss of responsiveness to hormone deprivation
therapy and aggressive course of the diseases has been addressed.
PMID- 26422100
TI - Application of serex-analysis for identification of human colon cancer antigens.
AB - BACKGROUND: Colorectal, lung and breast tumors are the most devastating and
frequent malignances in clinical oncology. SEREX-analysis of colon cancer leads
to identification of more than hundred antigens which are potential tumor
markers. With idea that immunoscreening with pool of allogeneic sera is more
productive for antigen isolation, SEREX-analysis was applied to four cases of
stages II-IV primary colon tumor and 22 new antigens were isolated. OBJECTIVE: To
characterize 22 primary colon cancer antigens isolated by SEREX-technique.
MATERIALS AND METHODS: Allogenic screening, real-time PCR analysis. RESULTS:
After allogeneic immunoscreening, for 5 of 22 (22%) isolated antigens were
confirmed colon cancer restricted serological profile solely positive for 14% of
tested colon cancer sera. Through these five antigens, KY-CC-17/beta-actin has
cytoskeleton function; KY-CC-14/ACTR1A and KY-CC-19/TSGA2 participate in
chromosome segregation; KY-CC-12/FKBP4 regulates steroid receptor function and KY
CC-15/PLRG1 is a component of spliceosome complex. For the last four antigens
tested were found aberrant mRNA expression in some cases of colon tumor.
CONCLUSION: The exploration of identified antigens may define suitable targets
for immunotherapy or diagnostic of colon cancer.
PMID- 26422101
TI - Modifying effects of lactoferrin in vitro on molecular phenotype of human breast
cancer cells.
AB - AIM: To assess the role of endogenous lactoferrin (LF) in the formation of the
molecular phenotype of human breast cancer (BC) cell lines with varying degrees
of malignancy, including cisplatin/doxorubicin resistant cell lines, and identify
possible impact of exogenous LF. MATERIALS AND METHODS: 5 breast cell lines of
different origin - MCF-10 A, MCF-7, including doxorubicin/cisplatin resistant
ones, T47D, MDA-MB-231, and MDA-MB-468. Immunocytochemistry: expression of LF, Ki
67, adhesion molecules E- and N-cadherin, CD44, CD24 rating the invasive
potential of cells. RESULTS: Expression of LF in human BC cell lines varies. It
is associated with the heterogeneity of molecular profiles of cell lines in terms
of adhesion. A link has been established between the level of LF expression in
the resistant cell line MCF-7/CP and MCF-7/Dox, features of their molecular
profile and invasive properties. Exogenous LF was shown to be capable of
modifying the molecular profile and invasive properties of all the studied cell
lines including resistant ones (MCF-7/CP and MCF-7/Dox). CONCLUSIONS: The
sensitivity of cytostatic-resistant cell lines (MCF-7/CP and MCF-7/Dox) tends to
increase under the influence of exogenous LF. It is likely that this effect is
due to LF-mediated inhibition of the expression of proteins associated with drug
resistance.
PMID- 26422102
TI - Enhanced cytotoxicity of photoexcited fullerene C60 and cisplatin combination
against drug-resistant leukemic cells.
AB - AIM: To evaluate the viability of leukemic cells sensitive (L1210S) and resistant
(L1210R) to cisplatin, ROS production and free cytosolic Ca(2+) concentration
under treatment with cisplatin or its combination with photoexcited fullerene
C60. METHODS: Cell viability was assessed by the MTT reduction assay. Light
emitting diode lamp (2.45 J/cm(2)) was used for photoexcitation of intracellular
accumulated fullerene C60. Free cytosolic calcium concentration ([Ca(2+)]i) and
ROS production in cells were estimated with the use of fluorescent probes Indo-1
and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), respectively. RESULTS:
It is shown that viability of L1210R cells wasn't changed under treatment with
cisplatin in concentration range 0.1-10 MUg/ml. 50% and 30% decrease of L1210S
cells were observed after 24 h of incubation with cisplatin at concentrations 5
and 1 MUg/ml, respectively. Intensification of extranuclear cytotoxic effects
(ROS production and [Ca(2+)]i increase) after treatment with 1 MUg/ml was
detected in L1210S, but not in L1210R cells. The most strongly pronounced
increase of ROS production and [Ca(2+)]i in both L1210 cell lines was revealed in
dynamics after combined treatment with cisplatin (1 MUg/ml) and photoexcited
fullerene C60 (10(-5) M) and was followed by decreased viability of not only
L1210S, but of L1210R cells as well.. CONCLUSION: Combined treatment with
photoexcited C60 and cisplatin allowed to decrease effective concentration of
cisplatin against parental L1210 cells and to increase sensibility of resistant
cells to the drug.
PMID- 26422103
TI - Aconitine-containing agent enhances antitumor activity of dichloroacetate against
Ehrlich carcinoma.
AB - Significant variability of anticancer efficacy of dichloroacetate (DCA)
stimulated an active search for the agents capable to enhance it antitumor
action. Therefore, the aim of this work is the study of capability of aconitine
containing antiangiogenic agent BC1 to enhance anticancer activity of DCA against
Ehrlich carcinoma. MATERIALS AND METHODS: DCA (total dose was 1.3 g/kg of b.w.)
and BC1 (total dose was 0.9 mg/kg of b.w.) were administered per os starting from
the 2(nd) and 3(rd) days, respectively (8 admini-strations for each agent).
Antitumor efficacy of agents was estimated. Lactate level, LDH activity and the
state of mitochondrial electron transport chain in tumor cells as well as
phagocytic activity and reactive oxygen species (ROS) production of tumor
associated macrophages (TAM) were studied. RESULTS: Combined administration of
DCA and VS1 resulted in 89.8% tumor growth inhibition (p < 0.001), what is by
22.5% (p < 0.05) higher that that of DCA alone. This combined treatment was
accompanied with a decrease of lactate level in tumor tissue by 30% (p < 0.05)
and significant elevation of LDH activity by 70% (p < 0.01). Increased level of
NO-Fe-S clusters and 2-fold reduction of Fe-S cluster content were revealed in
tumor tissue of mice after DCA and BC1 administration. It was shown that combined
therapy did not effect TAM quantity and their phagocytic activity but stimulated
ROS production by TAMs by 78% (p < 0.05) compared to this index in control
animals. CONCLUSION: Antiangiogenic agent VS1 in combination with DCA
considerably enhances antitumor activity of DCA via significant decrease of Fe-S
containing protein level resulted from substantial elevation of nitrosylation of
these proteins.
PMID- 26422104
TI - Anticancer effectiveness of vaccination based on xenogeneic embryo proteins
applied in different schedules.
AB - THE AIM: To evaluate anticancer activity of vaccination with chicken embryo
proteins (CEP) applied in different schedules. MATERIALS AND METHODS: C57Bl mice
were vaccinated with CEP before (prophylactic schedule) or after (different
therapeutic schedules with or without preliminary tumor removal) the Lewis lung
carcinoma cells transplantation. The latent period of tumor development, tumor
volume and metastasis rate were evaluated. RESULTS: Potent antimetastatic effect
of CEP-based vaccination was seen in case of therapeutic regimen after primary
tumor removal. The metastasis inhibition index (MII) reached 96.9 and 97.8% on
18(th) and 34(th) day after tumor removal, respectively. When CEP vaccination was
performed in the settings of therapeutic regimen without primary tumor removal
the anticancer effect was evident only if vaccinations started as early as 24 h
after the cancer cells injections. The highest MII achieved in such condition was
77.6%, tumor volume in the group of vaccinated animals was by 53.1-42.1% lower
than in the control tumor-bearing mice. CEP vaccination before tumor challenge
(prophylactic immunization) led to a statistically significant prolongation of
the latent period of tumor development, a reduction of tumor volume (35.8-48.8%
compared to control unvaccinated mice) and a marked inhibition of metastasis (MII
was 71.1%). CONCLUSION: Vaccination based on CEP exhibited both prophylactic and
therapeutic anticancer effects. The last one is more pronounced when the
vaccination starts shortly after the primary tumor resection.
PMID- 26422105
TI - Anticancer efficacy of allogeneic vaccine modified with progenitor neural cells
supernatant in rats with glioma 101.8.
AB - The aim of the work was to investigate the antitumor efficacy of allogeneic tumor
vaccine (ATV) modified with rat progenitor neural cell supernatant (RPNS) in rats
with glioma 101.8. MATERIALS AND METHODS: The study was performed on 74 white
random-bred rats. ATV was developed on the basis of glioma 101.8 cell suspension
modified with RPNS (0.02 or 0.10 mg/ml). RPNS was prepared from suspension made
from whole rat brain tissue on 14(th) (E14) day of gestation. Model of brain
glioma 101.8 was reproduced by intracerebral injection of glioma 101.8 cell
suspension. ATV was injected intraperitoneally in a volume of 0.2 ml per animal
once on the 10(th) day after tumor transplantation. For survival analysis Kaplan
Mayer multiple assessments method was used. Cytotoxic activity of rat
lymphocytes (effector cells) was evaluated in MTT-colorimetric test by
determining the state of mitochondrial dehydrogenase enzymes in target cells
(allogeneic glioma 101.8 cells). RESULTS: Intraperitoneal administration of ATV
modified with 0.10 mg/ml RPNS significantly increased mean survival time and
median survival of glioma-bearing rats compared with unvaccinated group (MST
(19.9 +/- 2.4), 21.4 days; versus MST (14.6 +/- 2.8); 14 days; p = 0.0002,
Gehan's - Wilcoxon test). Intraperitoneal administration of ATV modified with
0.10 mg/ml RPNS resulted in increased cytotoxic activity of immune cells of rats
with glioma in vitro compared with this index in unvaccinated group (p = 0.026, U
Mann - Whitney test). CONCLUSION: Antitumor effect of vaccination with RPNS
modified ATV is realized via increased cytotoxic activity of immune cells, what
could be used for further optimization of whole tumor cell vaccine.
PMID- 26422106
TI - TRP genes family expression in colorectal cancer.
AB - Colorectal cancer (CRC) is the most common cancer of the gastrointestinal tract.
Different factors are responsible for the development of CRC. Transient Receptor
Potential (TRP) which is an important component of calcium channel is associated
with several pathological conditions like cancer, neurodegenerative and
cardiovascular diseases. Thirty members of the family of TRP ion channel in
mammals have been determined till now. The aim of this study is to investigate
TRPM, TRPV and TRPC gene expression levels in tumor tissues of CRC patients and
to analyze the relationship of expression in tumor tissue of CRC with other known
prognostic factors. MATERIAL AND METHODS: In this study, 93 CRC patients were
included. The level of TRP gene expression in paraffin blocks of normal and
cancerous colorectal tissue samples were studied at the level of mRNA with Real
time PCR. RESULTS: The mRNA expression level of TRPV3, TRPV4, TRPV5, TRPM4 and
TRPC6 genes in 37 female and 56 male patients diagnosed with CRC was revealed
lower in tumor tissue as compared to normal tissue (p < 0.05). No statistically
significant differences of mRNA expression levels of other TRP genes were found.
CONCLUSIONS: TRP gene family like TRPV3, TRPV4, TRPV5, TRPM4 and TRPC6 may be
thought as potential genes contributing to tumorigenesis as their expression
decreases in CRC as compared to normal tissues.
PMID- 26422107
TI - Role of vascular endothelial growth factor in non-small cell lung cancer
pathogenesis.
AB - The angiogenesis is an important process in the pathogenesis of malignancies. It
is regulated by various growth factors, with the vascular endothelial growth
factor (VEGF) playing the central role. The aim of the present study was to
evaluate possible associations of functional VEGF -2578C>A, -634G>C, and +936C>T
polymorphisms with the risk for occurrence and progression of non-small cell lung
cancer (NSCLC) in patients living in Republic of Belarus. MATERIALS AND METHODS:
A total of 202 patients (147 males and 55 females) diagnosed as having the NSCLC.
The control group consisted of 336 individuals (245 males and 91 females) without
an oncopathology. The total DNA was isolated from peripheral blood. We
investigated the single nucleotide polymorphisms of VEGF (rs 2010963), (rs
699947), (rs 3025039). The genotyping was performed by PCR-RFLP analysis.
RESULTS: Our results revealed a marginally significant association of the -2578CC
genotype (p=0.002) with a greater degree of tumor spread (T2-T4). Heterozygous
genotypes -2578SA and +936ST carriers were included into the follow-up group
significantly more often (r=0.021 and r=0.012, respectively). Our study
demonstrate that VEGF -2578A/C and +936C/T polymorphisms are among the factors
determining the individual peculiarities of NSCLC course in this population and
can be used for clarifying the prognosis of the disease.
PMID- 26422108
TI - Plasma homocysteine, folate and vitamin B12 levels in patients with lung cancer.
AB - AIM: Disorders in the metabolism of homocysteine and B vitamins, which are
involved in a one-carbon transfer reaction and important for DNA synthesis and
methylation, have been hypothesized to be associated with carcinogenesis. The
purpose of this study is to evalu-ate the levels of homocysteine, vitamin B12 and
folic acid in patients with newly diagnosed lung cancer and determines whether
they might be used as an accurate tumor marker for monitoring the patients if
they are found to be elevated in lung cancer. MATERIALS AND METHODS: Forty male
patients with lung cancer were included in this study. Age-matched forty healthy
males who had not malignant disease or had not received any drug affecting plasma
homocysteine levels were selected as control group. Homocysteine, vitamin B12 and
folate levels were measured in the samples obtained from the patients and
controls. RESULTS: Mean age of the patients with lung cancer was 58.7 +/- 9.9
years. All the patients were cigarettes smokers. Mean daily consumption of
cigarettes was 2.0+/-0.7 packs and mean duration of smoking was 30 +/- 11 years.
Histologic type of carcinoma was found to be squamous cell carcinoma in 55%,
adenocarcinoma - in 35%, and small cell carcinoma - in 10% of the cases. Clinical
stage was stage IA in 20%, stage IB - in 20%, stage IIA - in 2.5%, stage IIB - in
10%, stage IIIA - in 12.5%, stage IIIB - in 20%, and stage IV - in 15% of the
cases. Mean homocysteine level was 15.3 +/- 7.3 umol/l in the patients with lung
cancer while 9.8 +/- 2.6 umol/l in controls. Homocysteine level was significantly
higher in the patients with lung cancer compared to control group (p < 0.001).
Mean folate level was 4.3 +/- 1.8 pg/ml in cancer cases while 6.1 +/- 2.3 pg/ml
in controls. That is to say, plasma folate levels were significantly lower in
cases of lung cancer compared to controls (p < 0.001). There was no significantly
difference between groups with regard to B12 levels (mean B12 level was 234 +/-
99 and 240 +/- 104 ng/ml in the patients with lung cancer and controls,
respectively, p = 0.78). Plasma homocysteine, vitamin B12 and folate levels did
not show significant difference with respect to histologic type of carcinoma. No
significant correlation was found between plasma homocysteine, vitamin B12,
folate levels and number of cigarettes smoked per day, duration of smoking, age
of the patient, and clinical stage of carcinoma. There was also no correlation
between number of cigarettes smoked per day, duration of smoking, age of the
patient and clinical stage of carcinoma. A possible inverse correlation between
plasma homocysteine, vitamin B12 and folate levels was not observed. CONCLUSION:
In conclusion, high plasma homocysteine and low folate levels could be associated
with lung cancer. However, further studies performed on large patient population
are needed.
PMID- 26422109
TI - Primary testicular lymphoma: a single centre experience.
AB - AIM: Primary testicular lymphoma (PTL) is an uncommon and aggressive form of
extranodal non-Hodgkin's lymphoma (NHL). We aimed to analyse the
clinicopathological characteristics and outcomes of our PTL cases. MATERIALS AND
METHODS: A review was made of the medical records of 339 NHL patients who were
treated in the Medical Oncology Department between January 2005 and December
2013. RESULTS: 8 PTL patients were identified from the 339 NHL patients. The
average age of the patients was 67.7 +/- 7.9 years (range 53-79 years). The mean
follow-up time was 24.8 months (range 7-98 months). Inguinal orchiectomy was
performed as a diagnostic and initial therapy and all the patients underwent 4-6
cycles of chemoimmunotherapy consisting of cyclophosphamide, doxorubicin,
vincristine and prednisone plus rituximab. 4 of 8 patients received intrathecal
prophylactic chemotherapy and 6 of 8 patients continued contralateral testis
irradiation. Relapse occured in only 1 patient in central nervous system after 6
months who had not received intrathecal prophylaxis. No contralateral testis
relapse was observed. CONCLUSIONS: Primary testicular NHL is an uncommon entity
and we evaluated 8 patients; with one relapse in central nervous system and no
relapse in the contralateral testis.
PMID- 26422110
TI - Rare case of intraintestinal stromal tumors in the patient with familial
adenomatous polyposis.
AB - AIM: To describe the case of metachronous gastrointestinal stromal tumors in a
proband with familial adenomatous polyposis (FAP), carrier of APC gene mutation
in codon 1309. MATERIAL AND METHODS: The physical examination, genealogical
analysis and molecular genetic analysis of peripheral blood in 15-years-old girl
with FAP and her sister, were carried out. Macroscopic, standard histological and
immunohistochemical study of surgical specimens - intraintestinal tumors of the
small intestine in proband was performed. RESULTS: Extraintestinal
manifestations, including congenital abnormalities of facial skeleton, typical
for Gardner's syndrome, were observed in the sisters with FAP as the addition
symptoms of the disease. Frameshift mutation in codon 1309 in the APC gene was
detected in these patients. A rare neoplasia - metachronous gastrointestinal
stromal tumor was found in proband 15 months after total colectomy for FAP. This
is the third case described in the accessible medical literature. CONCLUSION: The
possible role of APC gene mutation in the development of mesenchymal neoplasms is
discussed. The study of stromal tumors is important for understanding of their
pathogenesis that will enable to develop effective targeted therapy.
PMID- 26422111
TI - Intercorrelated Superhybrid of AgBr Supported on Graphitic-C3N4-Decorated
Nitrogen-Doped Graphene: High Engineering Photocatalytic Activities for Water
Purification and CO2 Reduction.
AB - AgBr nanoparticles supported on graphitic-C3N4-decorated nitrogen-doped graphene
intercorrelated ternary superhybrid composites (ACNNG-x) acting as a novel
visible-light driven photocatalyst are reported. Because of the fast interfacial
charge separation and photoelectrochemical performance, the representative of
ACNNG-50 superhybrid structure achieves high efficiency and stable photocatalytic
capability for organic contaminant degradation and CO2 reduction.
PMID- 26422113
TI - The role of surgery in the management of phantosmia.
PMID- 26422114
TI - Gastrointestinal Stromal Tumors: Imaging Features Before and After Treatment.
AB - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
the gastrointestinal tract, with most occurring in the stomach. GISTs may present
with clinical symptoms (eg, gastrointestinal bleeding) or may be found
incidentally at surgery, endoscopy, or imaging. At initial staging, GISTs often
appear as well-circumscribed, round, solid masses. Small tumors may appear solid,
whereas larger tumors may demonstrate central areas of necrosis. At follow-up
imaging, decreasing tumor attenuation at computed tomographic indicates treatment
response even in the setting of stable tumor size. Localized tumors are treated
with resection. Imatinib mesylate, a tyrosine kinase inhibitor, is typically
prescribed for metastatic disease and increasingly in a neoadjuvant role before
resection. Imaging plays a key role in the identification of GISTs, evaluation of
tumor extent and presence or absence of metastatic disease, and in assessing
response to therapy.
PMID- 26422112
TI - The impact of HLA class I and EBV latency-II antigen-specific CD8(+) T cells on
the pathogenesis of EBV(+) Hodgkin lymphoma.
AB - In 40% of cases of classical Hodgkin lymphoma (cHL), Epstein-Barr virus (EBV)
latency-II antigens [EBV nuclear antigen 1 (EBNA1)/latent membrane protein
(LMP)1/LMP2A] are present (EBV(+) cHL) in the malignant cells and antigen
presentation is intact. Previous studies have shown consistently that HLA-A*02 is
protective in EBV(+) cHL, yet its role in disease pathogenesis is unknown. To
explore the basis for this observation, gene expression was assessed in 33 cHL
nodes. Interestingly, CD8 and LMP2A expression were correlated strongly and, for
a given LMP2A level, CD8 was elevated markedly in HLA-A*02(-) versus HLA-A*02(+)
EBV(+) cHL patients, suggesting that LMP2A-specific CD8(+) T cell anti-tumoral
immunity may be relatively ineffective in HLA-A*02(-) EBV(+) cHL. To ascertain
the impact of HLA class I on EBV latency antigen-specific immunodominance, we
used a stepwise functional T cell approach. In newly diagnosed EBV(+) cHL, the
magnitude of ex-vivo LMP1/2A-specific CD8(+) T cell responses was elevated in HLA
A*02(+) patients. Furthermore, in a controlled in-vitro assay, LMP2A-specific
CD8(+) T cells from healthy HLA-A*02 heterozygotes expanded to a greater extent
with HLA-A*02-restricted compared to non-HLA-A*02-restricted cell lines. In an
extensive analysis of HLA class I-restricted immunity, immunodominant
EBNA3A/3B/3C-specific CD8(+) T cell responses were stimulated by numerous HLA
class I molecules, whereas the subdominant LMP1/2A-specific responses were
confined largely to HLA-A*02. Our results demonstrate that HLA-A*02 mediates a
modest, but none the less stronger, EBV-specific CD8(+) T cell response than non
HLA-A*02 alleles, an effect confined to EBV latency-II antigens. Thus, the
protective effect of HLA-A*02 against EBV(+) cHL is not a surrogate association,
but reflects the impact of HLA class I on EBV latency-II antigen-specific CD8(+)
T cell hierarchies.
PMID- 26422115
TI - From rare to common and back again: 60years of lysosomal dysfunction.
AB - Sixty years after its discovery, the lysosome is no longer considered as cell's
waste bin but as an organelle playing a central role in cell metabolism. Besides
its well known association with lysosomal storage disorders (mostly rare and life
threatening diseases), recent data have shown that the lysosome is also a player
in some of the most common conditions of our time; and, perhaps even most
important, it is not only a target for orphan drugs (rare disease therapeutic
approaches) but also a putative target to treat patients suffering from common
complex diseases worldwide. Here we review the striking associations linking rare
lysosomal storage disorders such as the well-known Gaucher disease, or even the
recently discovered, extremely rare Neuronal Ceroid Lipofuscinosis-11 and some of
the most frequent, multifaceted and complex disorders of modern society such as
cancer, Parkinson's disease and frontotemporal lobar degeneration.
PMID- 26422117
TI - Characterising intra- and inter-intrinsic network synchrony in combat-related
post-traumatic stress disorder.
AB - Soldiers with post-traumatic stress disorder (PTSD) exhibit elevated gamma-band
synchrony in left fronto-temporal cortex, and connectivity measures in these
regions correlate with comorbidities and PTSD severity, which suggests increased
gamma synchrony is related to symptomology. However, little is known about the
role of intrinsic, phase-synchronised networks in the disorder. Using
magnetoencephalography (MEG), we characterised spectral connectivity in the
default-mode, salience, visual, and attention networks during resting-state in a
PTSD population and a trauma-exposed control group. Intrinsic network
connectivity was examined in canonical frequency bands. We observed increased
inter-network synchronisation in the PTSD group compared with controls in the
gamma (30-80 Hz) and high-gamma range (80-150 Hz). Analyses of connectivity and
symptomology revealed that PTSD severity was positively associated with beta
synchrony in the ventral-attention-to-salience networks, and gamma synchrony
within the salience network, but also negatively correlated with beta synchrony
within the visual network. These novel results show that frequency-specific,
network-level atypicalities may reflect trauma-related alterations of ongoing
functional connectivity, and correlations of beta synchrony in attentional-to
salience and visual networks with PTSD severity suggest complicated network
interactions mediate symptoms. These results contribute to accumulating evidence
that PTSD is a complicated network-based disorder expressed as altered neural
interactions.
PMID- 26422116
TI - Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to
failed secondary ossification in mucopolysaccharidosis VII dogs.
AB - Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by
deficient beta-glucuronidase activity, which leads to the accumulation of
incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with
severe skeletal abnormalities, which are particularly prevalent in the spine.
Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal
development is associated with progressive spinal deformity and spinal cord
compression. The objectives of this study were to determine the earliest
postnatal developmental stage at which vertebral bone disease manifests in MPS
VII and to identify the underlying cellular basis of impaired cartilage-to-bone
conversion, using the naturally-occurring canine model. Control and MPS VII dogs
were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification
centers analyzed using micro-computed tomography, histology, qPCR, and protein
immunoblotting. Imaging studies and mRNA analysis of bone formation markers
established that secondary ossification commences between 9 and 14 days in
control animals, but not in MPS VII animals. mRNA analysis of differentiation
markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully
transition from proliferation to hypertrophy during this critical developmental
window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS
VII cells between 9 and 14 days-of-age, and biochemical assays revealed
abnormally high intra and extracellular GAG content in MPS VII epiphyseal
cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral
growth plates and primary ossification centers revealed no significant
abnormalities at either age. The results of this study establish that failed
vertebral bone formation in MPS VII can be traced to the failure of epiphyseal
chondrocytes to undergo hypertrophic differentiation at the appropriate
developmental stage, and suggest that aberrant processing of Sox9 protein may
contribute to this cellular dysfunction. These results also highlight the
importance of early diagnosis and therapeutic intervention to prevent the
progression of debilitating skeletal disease in MPS patients.
PMID- 26422118
TI - The Short French Internet Addiction Test Adapted to Online Sexual Activities:
Validation and Links With Online Sexual Preferences and Addiction Symptoms.
AB - The goal of this study was to investigate the psychometric properties of a French
version of the short Internet Addiction Test adapted to online sexual activities
(s-IAT-sex). The French version of the s-IAT-sex was administered to a sample of
401 men. The participants also completed a questionnaire that screened for sexual
addiction (PATHOS). The relationships of s-IAT-sex scores with time spent online
for online sexual activities (OSAs) and the types of OSAs favored were also
considered. Confirmatory analyses supported a two-factor model of s-IAT-sex,
corresponding to the factorial structure found in earlier studies that used the
short IAT. The first factor regroups loss of control and time management, whereas
the second factor regroups craving and social problems. Internal consistency for
each factor was evaluated with Cronbach's alpha coefficient, resulting in .87 for
Factor 1, .76 for Factor 2, and .88 for the global scale. Concurrent validity was
supported by relationships with symptoms of sexual addiction, types of OSAs
practiced, and time spent online for OSAs. The prevalence of sexual addiction
(measured by PATHOS) was 28.1% in the current sample of self-selected male OSA
users. The French version of the s-IAT-sex presents good psychometric properties
and constitutes a useful tool for researchers and practitioners.
PMID- 26422119
TI - Progressive cranial nerve involvement and grading of facial paralysis in gelsolin
amyloidosis.
AB - INTRODUCTION: Hereditary gelsolin amyloidosis (GA) is a rare condition caused by
the gelsolin gene mutation. The diagnostic triad includes corneal lattice
dystrophy (type 2), progressive bilateral facial paralysis, and cutis laxa.
Detailed information on facial paralysis in GA and the extent of cranial nerve
injury is lacking. METHODS: 29 GA patients undergoing facial corrective surgery
were interviewed, examined, and studied electroneurophysiologically. RESULTS: All
showed dysfunction of facial (VII) and trigeminal (V) nerves, two-thirds of
oculomotor (III) and hypoglossal (XII) nerves, and half of vestibulocochlear
(acoustic) (VIII) nerve. Clinical involvement of frontal, zygomatic, and buccal
facial nerve branches was seen in 97%, 83%, and 52% of patients, respectively.
Electromyography showed marked motor unit potential loss in facial musculature.
CONCLUSIONS: Cranial nerve involvement in GA is more widespread than previously
described, and correlates with age, severity of facial paralysis, and
electromyographic findings. We describe a grading method for bilateral facial
paralysis in GA, which is essential for evaluation of disease progression and the
need for treatment.
PMID- 26422120
TI - Sagittal range of motion of the thoracic spine using inertial tracking device and
effect of measurement errors on model predictions.
AB - Range of motion (ROM) of the thoracic spine has implications in patient
discrimination for diagnostic purposes and in biomechanical models for
predictions of spinal loads. Few previous studies have reported quite different
thoracic ROMs. Total (T1-T12), lower (T5-T12) and upper (T1-T5) thoracic, lumbar
(T12-S1), pelvis, and entire trunk (T1) ROMs were measured using an inertial
tracking device as asymptomatic subjects flexed forward from their neutral
upright position to full forward flexion. Correlations between body height and
the ROMs were conducted. An effect of measurement errors of the trunk flexion
(T1) on the model-predicted spinal loads was investigated. Mean of peak voluntary
total flexion of trunk (T1) was 118.4 +/- 13.9 degrees , of which 20.5 +/- 6.5
degrees was generated by flexion of the T1 to T12 (thoracic ROM), and the
remaining by flexion of the T12 to S1 (lumbar ROM) (50.2 +/- 7.0 degrees ) and
pelvis (47.8 +/- 6.9 degrees ). Lower thoracic ROM was significantly larger than
upper thoracic ROM (14.8 +/- 5.4 degrees versus 5.8 +/- 3.1 degrees ). There
were non-significant weak correlations between body height and the ROMs.
Contribution of the pelvis to generate the total trunk flexion increased from
~20% to 40% and that of the lumbar decreased from ~60% to 42% as subjects flexed
forward from upright to maximal flexion while that of the thoracic spine remained
almost constant (~16% to 20%) during the entire movement. Small uncertainties (+/
5 degrees ) in the measurement of trunk flexion angle resulted in considerable
errors (~27%) in the model-predicted spinal loads only in activities involving
small trunk flexion.
PMID- 26422121
TI - Metabarcoding approach for nonindigenous species surveillance in marine coastal
waters.
AB - In this study, high-throughput sequencing (HTS) metabarcoding was applied for the
surveillance of plankton communities within the southeastern (SE) Baltic Sea
coastal zone. These results were compared with those from routine monitoring
survey and morphological analyses. Four of five nonindigenous species found in
the samples were identified exclusively by metabarcoding. All of them are
considered as invasive in the Baltic Sea with reported impact on the ecosystem
and biodiversity. This study indicates that, despite some current limitations,
HTS metabarcoding can provide information on the presence of exotic species and
advantageously complement conventional approaches, only requiring the same
monitoring effort as before. Even in the currently immature status of HTS, this
combination of HTS metabarcoding and observational records is recommended in the
early detection of marine pests and delivery of the environmental status metrics
of nonindigenous species.
PMID- 26422122
TI - Bioassessment of marine sediment quality using meiofaunal assemblages in a semi
enclosed bay.
AB - In order to assess marine sediment quality of a semi-enclosed bay, sediment and
meiofaunal samples were analyzed at 35 stations in coastal waters of Bohai Bay,
China. Concentrations of heavy metals (Cd, Cr, Cu, Ni, Pb, Zn, Co and Mn) in
sediment were measured and the Hakanson potential ecological risk index coupled
with the ratio of nematodes to copepods (N/C ratio) was used. Results showed that
the concentration of Mn was the highest while Cd was the main risk contributor.
The Hakanson potential ecological risk index indicated that all pollutants posed
low risks in the study area. However, the N/C ratio exhibited different results
compared with Hakanson potential ecological risk index. BIOENV analysis
identified the concentration of Ni and sediment grain size as the most important
environmental variables influencing meiofaunal assemblages. The present study
indicated that, in marine sediment quality assessments, meiofaunal assemblages
should be involved besides pollutant concentrations.
PMID- 26422123
TI - Application of baited remote underwater video stations to assess benthic coverage
in the Persian Gulf.
AB - A baited remote underwater video station (BRUVS) is generally considered an
appropriate sampling tool for fish. The applicability of BRUVS to determine the
substrate coverage was assessed by comparing stills from BRUVS videos to
traditional point intercept transect (PIT) data to estimate percentage cover (PC)
of different benthic substrate categories. Mean PCs of hard corals, rock, sand,
and coral growth forms yielded statistically identical values with the two survey
methods, while PCs of motile epibenthic invertebrates were underestimated by
BRUVS in areas of both high and moderate relief. Yet, multivariate analyses
revealed that the two methods yield similar substrate assemblage in an area of
moderate relief. Results of our study suggest that the BRUVS can be effectively
used to quantify both the presence/absence of a basic set of benthic habitat
characteristics and diversity of coral growth forms on coral reefs in the Persian
Gulf.
PMID- 26422124
TI - Dry eyes and AIs: If you don't ask you won't find out.
AB - OBJECTIVES: Our objective was to investigate the hypothesis that women on
adjuvant aromatase inhibitors (AIs) for treatment of breast cancer have a higher
prevalence of dry eye syndrome (DES) compared with controls. MATERIALS AND
METHODS: Exposure and control groups were recruited. A cross sectional
questionnaire-based study was performed. Demographic data and medical histories
were collected. The presence of dry eye syndrome was determined by the ocular
surface disease index (OSDI). The Functional Assessment of Cancer Treatment -
Endocrine Subscale (FACT-ES) was performed to investigate correlations with other
side effects of AIs. RESULTS: 93 exposure group and 100 control group
questionnaires were included. The groups were similar in all demographic
variables. The prevalence of dry eye syndrome was 35% (exposure) and 18%
(control) (p < 0.01, OR 2.5). AIs were the only factor associated with dry eyes.
The OSDI score was negatively correlated with the total FACT-ES score and
positively correlated with duration of treatment. CONCLUSION: Our study is the
first to use a validated questionnaire to assess for DES in this population. DES
is significantly more prevalent in women on AIs compared with controls. This is a
newly emerging, and easily treated side effect of AIs. Self-reporting of dry eye
symptoms underestimates the prevalence of DES with AIs. We recommend routine
screening of patients on AIs with the OSDI with the aim of improving patient
quality of life and possibly adherence.
PMID- 26422125
TI - Exploring information provision in reconstructive breast surgery: A qualitative
study.
AB - OBJECTIVE: Women considering reconstructive breast surgery (RBS) require adequate
information to make informed treatment decisions. This study explored patients'
and health professionals' (HPs) perceptions of the adequacy of information
provided for decision-making in RBS. METHODS: Semi-structured interviews with a
purposive sample of patients who had undergone RBS and HPs providing specialist
care explored participants' experiences of information provision prior to RBS.
RESULTS: Professionals reported providing standardised verbal, written and
photographic information about the process and outcomes of surgery. Women, by
contrast, reported varying levels of information provision. Some felt fully
informed but others perceived they had received insufficient information about
available treatment options or possible outcomes of surgery to make an informed
decision. CONCLUSIONS: Women need adequate information to make informed decisions
about RBS and current practice may not meet women's needs. Minimum agreed
standards of information provision, especially about alternative types of
reconstruction, are recommended to improve decision-making in RBS.
PMID- 26422127
TI - Othering the Chronically Ill: A Discourse Analysis of New Zealand Health Policy
Documents.
AB - It is widely recognized that chronic illnesses pose significant challenges for
health care systems around the world. In response, most governments have set
health policies in order to manage (or better, reduce) demand and improve the
health of their populations. A discourse analysis of four policy documents that
shape these strategies in New Zealand reveals that the policies construct the
chronically ill as "others," that is, as deviant or different from the "normal"
population. The discourse further serves to blame the chronically ill both for
being sick, and for placing a serious financial burden on society. We identify
problems that arise from this discourse. They relate to (a) the fact that chronic
illnesses are so prevalent, (b) the fallacy of categorizing all chronic illnesses
as the same,
PMID- 26422126
TI - Development of hyperdynamic circulation and response to beta-blockers in
compensated cirrhosis with portal hypertension.
AB - Nonselective beta-blockers are useful to prevent bleeding in patients with
cirrhosis and large varices but not to prevent the development of varices in
those with compensated cirrhosis and portal hypertension (PHT). This suggests
that the evolutionary stage of PHT may influence the response to beta-blockers.
To characterize the hemodynamic profile of each stage of PHT in compensated
cirrhosis and the response to beta-blockers according to stage, we performed a
prospective, multicenter (tertiary care setting), cross-sectional study. Hepatic
venous pressure gradient (HVPG) and systemic hemodynamic were measured in 273
patients with compensated cirrhosis before and after intravenous propranolol
(0.15 mg/kg): 194 patients had an HVPG >=10 mm Hg (clinically significant PHT
[CSPH]), with either no varices (n = 80) or small varices (n = 114), and 79 had
an HVPG >5 and <10 mm Hg (subclinical PHT). Patients with CSPH had higher liver
stiffness (P < 0.001), worse Model for End-Stage Liver Disease score (P < 0.001),
more portosystemic collaterals (P = 0.01) and splenomegaly (P = 0.01) on
ultrasound, and lower platelet count (P < 0.001) than those with subclinical PHT.
Patients with CSPH had lower systemic vascular resistance (1336 +/- 423 versus
1469 +/- 335 dyne . s . cm(-5) , P < 0.05) and higher cardiac index (3.3 +/- 0.9
versus 2.8 +/- 0.4 L/min/m(2) , P < 0.01). After propranolol, the HVPG decreased
significantly in both groups, although the reduction was greater in those with
CSPH (-16 +/- 12% versus -8 +/- 9%, P < 0.01). The HVPG decreased >=10% from
baseline in 69% of patients with CSPH versus 35% with subclinical PHT (P < 0.001)
and decreased >=20% in 40% versus 13%, respectively (P = 0.001). CONCLUSION:
Patients with subclinical PHT have less hyperdynamic circulation and
significantly lower portal pressure reduction after acute beta-blockade than
those with CSPH, suggesting that beta-blockers are more suitable to prevent
decompensation of cirrhosis in patients with CSPH than in earlier stages.
PMID- 26422128
TI - Prorating WAIS - IV summary scores for patients with relapsing-remitting multiple
sclerosis.
AB - We evaluated the utility of prorating appropriate combinations of two, six and
eight Wechsler Adult Intelligence Scale - Fourth Edition (WAIS - IV) subtests for
estimating the Verbal Comprehension Index (VCI), Perceptual Reasoning Index
(PRI), Full Scale IQ (FSIQ) and General Ability Index (GAI) in a sample of
individuals diagnosed with multiple sclerosis (MS). Forty-eight outpatients
completed the WAIS - IV and Wechsler Memory Scale - Fourth Edition (WMS - IV) as
part of a comprehensive neuropsychological battery. Means for age, education and
duration of diagnosis were 42.35, 14.21 and 8.30 years, respectively. Paired t
tests showed no significant differences between prorated and standard means for
VCI (93.46 vs. 93.73), PRI (90.19 vs. 89.44), FSIQ (88.53 vs. 88.47) or GAI
(90.56 vs. 90.65). Correlations between prorated and standard composites were
>=0.89 in every instance. Correlations between the standard and prorated
composites and education, disability status and WMS - IV indexes did not reveal a
single contrast, where the correlations were significantly different. The present
findings support the use of the two-subtest VCI and PRI composites and the eight
subtest FSIQ and four-subtest GAI in the assessment of patients with MS.
PMID- 26422130
TI - A NIR-remote controlled upconverting nanoparticle: an improved tool for living
cell dye-labeling.
AB - In living cells, due to the selective permeability and complicated cellular
environment, the uptake efficiency and fluorescence decay of organic dyes during
dye-labeling may be influenced, which may eventually result in poor fluorescent
imaging. In this work, a protocol of UCNs@mSiO2-(FA and Azo) core-shell
nanocarriers was designed and prepared successfully. The core-shell nanocarriers
were assembled from two parts, including a mesoporous silica shell surface
modified by folate (FA) and azobenzene (Azo), and an upconverting nanocrystal
(UCN) core. The mesoporous silica shell is used for loading organic dyes and
conjugating folate which helps to enhance the cellular uptake of nanocarriers.
The UCN core works as a transducer to convert near infrared (NIR) light to local
UV and visible light to activate a back-and-forth wagging motion of azobenzene
molecules on the surface, while the azobenzene acts as a molecular impeller for
propelling the release of organic dyes. The nanocarriers of loading organic dyes
can maintain the stability of the fluorescent imaging effect better than free
organic dyes. The experimental results show that with the help of the
nanoparticle, cell uptake efficiency of the model dyes of rhodamine and 4', 6
diamidino-2-phenylindole (DAPI) was significantly improved. The release of dyes
can only be triggered by NIR light exposure and their quantity is highly
dependent on the duration of NIR light exposure, thus realizing NIR-regulated dye
release spatiotemporally. Our work may open a novel avenue for precisely
controlling UCN-based living cell imaging in biotechnology and diagnostics, as
well as studying cell dynamics, cell-cell interactions, and tissue morphogenesis.
PMID- 26422129
TI - Noise-Enhanced Vestibular Input Improves Dynamic Walking Stability in Healthy
Subjects.
AB - BACKGROUND: White noise galvanic vestibular stimulation (GVS) is thought to
enhance the sensitivity of vestibular organs. OBJECTIVE: To examine the effects
of noise-enhanced vestibular input on the walking performance in healthy subjects
walking with eyes closed. METHODS: Walking performance of 17 healthy subjects
(mean age 28.8 +/- 1.7 years) at slow, preferred, and fast speeds was examined
during three different conditions: (1) walking with eyes open (EO) as baseline
condition, (2) walking with eyes closed and sham noisy GVS (EC), and (3) walking
with eyes closed and non-zero amplitude noisy GVS set to 80% of the individual
sensory threshold for GVS (EC-GVS). Ten gait parameters were examined: stride
time, stride length, base of support, swing time percentage, double support time
percentage as well as gait asymmetry, bilateral phase coordination and the
coefficient of variation (CV) of stride time, stride length and base of support.
RESULTS: Noisy GVS improved stride time CV by 36% (p < 0.034), stride length CV
by 31% (p < 0.037), base of support CV by 14% (p < 0.009), and bilateral phase
coordination by 23% (p < 0.034). The ameliorating effects of noisy GVS on
locomotion function were primarily observable during slow walking speeds.
CONCLUSION: Noise-enhanced vestibular input is effective in improving locomotion
function and is accompanied by a subjectively felt improvement of walking
balance. It predominantly targets the variability and bilateral coordination
characteristics of the walking pattern, which are critically linked to dynamic
walking stability. Noisy GVS might present an effective treatment option to
improve walking performance in patients with bilateral vestibular dysfunction.
PMID- 26422131
TI - Cytotoxic Barrigenol-like Triterpenoids from an Extract of Cyrilla racemiflora
Housed in a Repository.
AB - Two new [(+)-cyrillins A (1) and B (2)] and four known barrigenol-like
triterpenoids (3-6), along with betulinic acid and (+)-3beta-O-trans
feruloylbetulinic acid, were isolated from a sample-restricted CH2Cl2-soluble
extract of the bark of Cyrilla racemiflora, collected in Dominica. The structures
of the new compounds were elucidated by interpretation of their spectroscopic
data, and the absolute configuration of the cyclic 1,2-diol unit of (+)-cyrillin
A (1) was ascertained by analysis of the electronic circular dichroism (ECD)
spectrum induced with [Mo2(OAc)4]. In the case of (+)-cyrillin B (2), which was
found to contain a diangeloylated glucose residue, the structure proposed was
supported by analysis of its MS(2) and MS(3) spectra. All compounds isolated were
evaluated for their cytotoxicity against HT-29 human colon cancer cells, and the
known compound, (+)-barringtogenol B (3), was found to be the most potent,
exhibiting an IC50 value of 1.7 MUM. This compound also showed inhibitory
activity toward the CCD-112CoN human normal colon cell line, with an IC50 value
of 5.9 MUM, indicating a lack of cytotoxic selectivity.
PMID- 26422133
TI - Histone modification and chromatin remodeling during NER.
AB - Here we review our developments of and results with high resolution studies on
global genome nucleotide excision repair (GG-NER) in Saccharomyces cerevisiae.
Technologies were developed to examine NER at nucleotide resolution in yeast
sequences of choice and to determine how these related to local changes in
chromatin. We focused on how GG-NER relates to histone acetylation for its
functioning and we identified the histone acetyltransferase Gcn5 and acetylation
at lysines 9/14 of histone H3 as a major factor in enabling efficient repair.
Factors influencing this Gcn5-mediated event are considered which include Rad16,
a GG-NER specific SWI/SNF factor and the yeast histone variant of H2AZ (Htz1). We
describe results employing primarily MFA2 as a model gene, but also those with
URA3 located at subtelomeric sequences. In the latter case we also see a role for
acetylation at histone H4. We then consider the development of a high resolution
genome-wide approach that enables one to examine correlations between histone
modifications and the NER of UV-induced cyclobutane pyrimidine dimers throughout
entire yeast genome. This is an approach that will enable rapid advances in
understanding the complexities of how compacted chromatin in chromosomes is
processed to access DNA damage before it is returned to its pre-damaged status to
maintain epigenetic codes.
PMID- 26422132
TI - DNA excision repair at telomeres.
AB - DNA damage is caused by either endogenous cellular metabolic processes such as
hydrolysis, oxidation, alkylation, and DNA base mismatches, or exogenous sources
including ultraviolet (UV) light, ionizing radiation, and chemical agents.
Damaged DNA that is not properly repaired can lead to genomic instability,
driving tumorigenesis. To protect genomic stability, mammalian cells have evolved
highly conserved DNA repair mechanisms to remove and repair DNA lesions.
Telomeres are composed of long tandem TTAGGG repeats located at the ends of
chromosomes. Maintenance of functional telomeres is critical for preventing
genome instability. The telomeric sequence possesses unique features that
predispose telomeres to a variety of DNA damage induced by environmental
genotoxins. This review briefly describes the relevance of excision repair
pathways in telomere maintenance, with the focus on base excision repair (BER),
nucleotide excision repair (NER), and mismatch repair (MMR). By summarizing
current knowledge on excision repair of telomere damage and outlining many
unanswered questions, it is our hope to stimulate further interest in a better
understanding of excision repair processes at telomeres and in how these
processes contribute to telomere maintenance.
PMID- 26422136
TI - DNA damage mediated transcription arrest: Step back to go forward.
AB - The disturbance of DNA helix conformation by bulky DNA damage poses hindrance to
transcription elongating due to stalling of RNA polymerase at transcription
blocking lesions. Stalling of RNA polymerase provokes the formation of R-loops,
i.e. the formation of a DNA-RNA hybrid and a displaced single stranded DNA strand
as well as displacement of spliceosomes. R-loops are processed into DNA single
and double strand breaks by NER factors depending on TC-NER factors leading to
genome instability. Moreover, stalling of RNA polymerase induces a strong signal
for cell cycle arrest and apoptosis. These toxic and mutagenic effects are
counteracted by a rapid recruitment of DNA repair proteins to perform
transcription coupled nucleotide excision repair (TC-NER) to remove the blocking
DNA lesions and to restore transcription. Recent studies have highlighted the
role of backtracking of RNA polymerase to facilitate TC-NER and identified novel
factors that play key roles in TC-NER and in restoration of transcription. On the
molecular level these factors facilitate stability of the repair complex by
promotion and regulation of various post-translational modifications of NER
factors and chromatin substrate. In addition, the continuous flow of new factors
that emerge from screening assays hints to several regulatory levels to safeguard
the integrity of transcription elongation after disturbance by DNA damage that
have yet to be explored.
PMID- 26422135
TI - XPC: Going where no DNA damage sensor has gone before.
AB - XPC has long been considered instrumental in DNA damage recognition during global
genome nucleotide excision repair (GG-NER). While this recognition is crucial for
organismal health and survival, as XPC's recognition of lesions stimulates global
genomic repair, more recent lines of research have uncovered many new non
canonical pathways in which XPC plays a role, such as base excision repair (BER),
chromatin remodeling, cell signaling, proteolytic degradation, and cellular
viability. Since the first discovery of its yeast homolog, Rad4, the involvement
of XPC in cellular regulation has expanded considerably. Indeed, our
understanding appears to barely scratch the surface of the incredible potential
influence of XPC on maintaining proper cellular function. Here, we first review
the canonical role of XPC in lesion recognition and then explore the new world of
XPC function.
PMID- 26422134
TI - Facilitation of base excision repair by chromatin remodeling.
AB - Base Excision Repair (BER) is a conserved, intracellular DNA repair system that
recognizes and removes chemically modified bases to insure genomic integrity and
prevent mutagenesis. Aberrant BER has been tightly linked with a broad spectrum
of human pathologies, such as several types of cancer, neurological degeneration,
developmental abnormalities, immune dysfunction and aging. In the cell, BER must
recognize and remove DNA lesions from the tightly condensed, protein-coated
chromatin. Because chromatin is necessarily refractory to DNA metabolic
processes, like transcription and replication, the compaction of the genomic
material is also inhibitory to the repair systems necessary for its upkeep.
Multiple ATP-dependent chromatin remodelling (ACR) complexes play essential roles
in modulating the protein-DNA interactions within chromatin, regulating
transcription and promoting activities of some DNA repair systems, including
double-strand break repair and nucleotide excision repair. However, it remains
unclear how BER operates in the context of chromatin, and if the chromatin
remodelling processes that govern transcription and replication also actively
regulate the efficiency of BER. In this review we highlight the emerging role of
ACR in regulation of BER.
PMID- 26422137
TI - Histone ubiquitylation and its roles in transcription and DNA damage response.
AB - DNA in human cells is constantly assaulted by endogenous and exogenous DNA
damaging agents. It is vital for the cell to respond rapidly and precisely to DNA
damage to maintain genome integrity and reduce the risk of mutagenesis.
Sophisticated reactions occur in chromatin surrounding the damaged site leading
to the activation of DNA damage response (DDR), including transcription
reprogramming, cell cycle checkpoint, and DNA repair. Histone proteins around the
DNA damage play essential roles in DDR, through extensive post-translational
modifications (PTMs) by a variety of modifying enzymes. One PTM on histones, mono
ubiquitylation, has emerged as a key player in cellular response to DNA damage.
In this review, we will (1) briefly summarize the history of histone H2A and H2B
ubiquitylation (H2Aub and H2Bub, respectively), (2) discuss their roles in
transcription, and (3) their functions in DDR.
PMID- 26422138
TI - In vitro Autoradiographic Analysis of Regional Changes in Estrogen Receptor Alpha
in the Brains of Cycling Female Rats.
AB - BACKGROUND/AIMS: The contributions of the three principal ovarian steroid
hormones (estradiol, progesterone and testosterone) to the regulation of estrogen
receptor alpha (ERalpha) levels in the rat brain were examined during the estrous
cycle. METHODS: Receptor concentrations were measured using an in vitro
autoradiographic technique designed to separately quantify free, unoccupied
receptors and receptors 'occupied' by (bound to) endogenous hormone. RESULTS:
ERalpha occupation increased at proestrus and declined at estrus, reflecting
changes in circulating estradiol and testosterone levels. Total ERalpha content
followed a pattern that was the inverse of the occupation data, falling over the
night of proestrus. Between 2.00 and 10.00 a.m. on the day of estrus, total
ERalpha concentrations recovered in all brain regions except the ventromedial
nucleus (VMN), in which ERalpha binding remained depressed at estrus.
Administration of the progesterone antagonist mifepristone on the afternoon of
proestrus resulted in recovery of ERalpha levels in the VMN by the morning of
estrus, consistent with the hypothesis that the preovulatory progesterone surge
selectively inhibits VMN ERalpha expression. Residual ERalpha occupation observed
at estrus, when estradiol is not detectable in the serum, likely reflects
intracranial aromatization of circulating androgens, since the pattern of
receptor occupation observed at this stage of the cycle could be reproduced in
ovariectomized rats by replacement with testosterone. CONCLUSION: These findings
indicate that ERalpha binding in the brain fluctuates during the rat estrous
cycle in a region-specific manner and suggest that local aromatization of
testosterone may contribute significantly to ERalpha occupation when circulating
estradiol levels are low.
PMID- 26422140
TI - Analysis of Chaotic Resonance in Izhikevich Neuron Model.
AB - In stochastic resonance (SR), the presence of noise helps a nonlinear system
amplify a weak (sub-threshold) signal. Chaotic resonance (CR) is a phenomenon
similar to SR but without stochastic noise, which has been observed in neural
systems. However, no study to date has investigated and compared the
characteristics and performance of the signal responses of a spiking neural
system in some chaotic states in CR. In this paper, we focus on the Izhikevich
neuron model, which can reproduce major spike patterns that have been
experimentally observed. We examine and classify the chaotic characteristics of
this model by using Lyapunov exponents with a saltation matrix and Poincare
section methods in order to address the measurement challenge posed by the state
dependent jump in the resetting process. We found the existence of two
distinctive states, a chaotic state involving primarily turbulent movement and an
intermittent chaotic state. In order to assess the signal responses of CR in
these classified states, we introduced an extended Izhikevich neuron model by
considering weak periodic signals, and defined the cycle histogram of neuron
spikes as well as the corresponding mutual correlation and information. Through
computer simulations, we confirmed that both chaotic states in CR can sensitively
respond to weak signals. Moreover, we found that the intermittent chaotic state
exhibited a prompter response than the chaotic state with primarily turbulent
movement.
PMID- 26422139
TI - DJ-1 Protects Pancreatic Beta Cells from Cytokine- and Streptozotocin-Mediated
Cell Death.
AB - A hallmark feature of type 1 and type 2 diabetes mellitus is the progressive
dysfunction and loss of insulin-producing pancreatic beta cells, and inflammatory
cytokines are known to trigger beta cell death. Here we asked whether the anti
oxidant protein DJ-1 encoded by the Parkinson's disease gene PARK7 protects islet
cells from cytokine- and streptozotocin-mediated cell death. Wild type and DJ-1
knockout mice (KO) were treated with multiple low doses of streptozotocin (MLDS)
to induce inflammatory beta cell stress and cell death. Subsequently, glucose
tolerance tests were performed, and plasma insulin as well as fasting and random
blood glucose concentrations were monitored. Mitochondrial morphology and number
of insulin granules were quantified in beta cells. Moreover, islet cell damage
was determined in vitro after streptozotocin and cytokine treatment of isolated
wild type and DJ-1 KO islets using calcein AM/ethidium homodimer-1 staining and
TUNEL staining. Compared to wild type mice, DJ-1 KO mice became diabetic
following MLDS treatment. Insulin concentrations were substantially reduced, and
fasting blood glucose concentrations were significantly higher in MLDS-treated DJ
1 KO mice compared to equally treated wild type mice. Rates of beta cell
apoptosis upon MLDS treatment were twofold higher in DJ-1 KO mice compared to
wild type mice, and in vitro inflammatory cytokines led to twice as much beta
cell death in pancreatic islets from DJ-1 KO mice versus those of wild type mice.
In conclusion, this study identified the anti-oxidant protein DJ-1 as being
capable of protecting pancreatic islet cells from cell death induced by an
inflammatory and cytotoxic setting.
PMID- 26422141
TI - An Alternative Method to Facilitate cDNA Cloning for Expression Studies in
Mammalian Cells by Introducing Positive Blue White Selection in Vaccinia
Topoisomerase I-Mediated Recombination.
AB - One of the most basic techniques in biomedical research is cDNA cloning for
expression studies in mammalian cells. Vaccinia topoisomerase I-mediated cloning
(TOPO cloning by Invitrogen) allows fast and efficient recombination of PCR
amplified DNAs. Among TOPO vectors, a pcDNA3.1 directional cloning vector is
particularly convenient, since it can be used for expression analysis immediately
after cloning. However, I found that the cloning efficiency was reduced when RT
PCR products were used as inserts (about one-quarter). Since TOPO vectors accept
any PCR products, contaminating fragments in the insert DNA create negative
clones. Therefore, I designed a new mammalian expression vector enabling positive
blue white selection in Vaccinia topoisomerase I-mediated cloning. The method
utilized a short nontoxic LacZalpha peptide as a linker for GFP fusion. When
cDNAs were properly inserted into the vector, minimal expression of the fusion
proteins in E. coli (harboring lacZDeltaM15) resulted in formation of blue
colonies on X-gal plates. This method improved both cloning efficiency (75%) and
directional cloning (99%) by distinguishing some of the negative clones having
non-cording sequences, since these inserts often disturbed translation of
lacZalpha. Recombinant plasmids were directly applied to expression studies using
GFP as a reporter. Utilization of the P2A peptide allowed for separate expression
of GFP. In addition, the preparation of Vaccinia topoisomerase I-linked vectors
was streamlined, which consisted of successive enzymatic reactions with a single
precipitation step, completing in 3 hr. The arrangement of unique restriction
sites enabled further modification of vector components for specific
applications. This system provides an alternative method for cDNA cloning and
expression in mammalian cells.
PMID- 26422143
TI - Why Robots Should Be Social: Enhancing Machine Learning through Social Human
Robot Interaction.
AB - Social learning is a powerful method for cultural propagation of knowledge and
skills relying on a complex interplay of learning strategies, social ecology and
the human propensity for both learning and tutoring. Social learning has the
potential to be an equally potent learning strategy for artificial systems and
robots in specific. However, given the complexity and unstructured nature of
social learning, implementing social machine learning proves to be a challenging
problem. We study one particular aspect of social machine learning: that of
offering social cues during the learning interaction. Specifically, we study
whether people are sensitive to social cues offered by a learning robot, in a
similar way to children's social bids for tutoring. We use a child-like social
robot and a task in which the robot has to learn the meaning of words. For this a
simple turn-based interaction is used, based on language games. Two conditions
are tested: one in which the robot uses social means to invite a human teacher to
provide information based on what the robot requires to fill gaps in its
knowledge (i.e. expression of a learning preference); the other in which the
robot does not provide social cues to communicate a learning preference. We
observe that conveying a learning preference through the use of social cues
results in better and faster learning by the robot. People also seem to form a
"mental model" of the robot, tailoring the tutoring to the robot's performance as
opposed to using simply random teaching. In addition, the social learning shows a
clear gender effect with female participants being responsive to the robot's
bids, while male teachers appear to be less receptive. This work shows how
additional social cues in social machine learning can result in people offering
better quality learning input to artificial systems, resulting in improved
learning performance.
PMID- 26422142
TI - Entamoeba histolytica Dmc1 Catalyzes Homologous DNA Pairing and Strand Exchange
That Is Stimulated by Calcium and Hop2-Mnd1.
AB - Meiosis depends on homologous recombination (HR) in most sexually reproducing
organisms. Efficient meiotic HR requires the activity of the meiosis-specific
recombinase, Dmc1. Previous work shows Dmc1 is expressed in Entamoeba
histolytica, a eukaryotic parasite responsible for amoebiasis throughout the
world, suggesting this organism undergoes meiosis. Here, we demonstrate Dmc1
protein is expressed in E. histolytica. We show that purified ehDmc1 forms
presynaptic filaments and catalyzes ATP-dependent homologous DNA pairing and DNA
strand exchange over at least several thousand base pairs. The DNA pairing and
strand exchange activities are enhanced by the presence of calcium and the
meiosis-specific recombination accessory factor, Hop2-Mnd1. In combination,
calcium and Hop2-Mnd1 dramatically increase the rate of DNA strand exchange
activity of ehDmc1. The biochemical system described herein provides a basis on
which to better understand the role of ehDmc1 and other HR proteins in E.
histolytica.
PMID- 26422145
TI - Development and implementation of a remote-sensing and in situ data-assimilating
version of CMAQ for operational PM2.5 forecasting. Part 1: MODIS aerosol optical
depth (AOD) data-assimilation design and testing.
AB - This two-part paper reports on the development, implementation, and improvement
of a version of the Community Multi-Scale Air Quality (CMAQ) model that
assimilates real-time remotely-sensed aerosol optical depth (AOD) information and
ground-based PM2.5 monitor data in routine prognostic application. The model is
being used by operational air quality forecasters to help guide their daily
issuance of state or local-agency-based air quality alerts (e.g. action days,
health advisories). Part 1 describes the development and testing of the initial
assimilation capability, which was implemented offline in partnership with NASA
and the Visibility Improvement State and Tribal Association of the Southeast
(VISTAS) Regional Planning Organization (RPO). In the initial effort, MODIS
derived aerosol optical depth (AOD) data are input into a variational data
assimilation scheme using both the traditional Dark Target and relatively new
"Deep Blue" retrieval methods. Evaluation of the developmental offline version,
reported in Part 1 here, showed sufficient promise to implement the capability
within the online, prognostic operational model described in Part 2. In Part 2,
the addition of real-time surface PM2.5 monitoring data to improve the
assimilation and an initial evaluation of the prognostic modeling system across
the continental United States (CONUS) is presented. IMPLICATIONS: Air quality
forecasts are now routinely used to understand when air pollution may reach
unhealthy levels. For the first time, an operational air quality forecast model
that includes the assimilation of remotely-sensed aerosol optical depth and
ground based PM2.5 observations is being used. The assimilation enables
quantifiable improvements in model forecast skill, which improves confidence in
the accuracy of the officially-issued forecasts. This helps air quality
stakeholders be more effective in taking mitigating actions (reducing power
consumption, ride-sharing, etc.) and avoiding exposures that could otherwise
result in more serious air quality episodes or more deleterious health effects.
PMID- 26422144
TI - Sternal Wound Infection after Cardiac Surgery: Management and Outcome.
AB - BACKGROUND: Sternal Wound Infection (SWI) is a severe complication after cardiac
surgery. Debridement associated with primary closure using Redon drains (RD) is
an effective treatment, but data on RD management and antibiotic treatment are
scarce. METHODS: We performed a single-center analysis of consecutive patients
who were re-operated for SWI between 01/2009 and 12/2012. All patients underwent
a closed drainage with RD (CDRD). Patients with endocarditis or those who died
within the first 45 days were excluded from management analysis. RD fluid was
cultured twice weekly. Variables recorded were clinical and biological data at
SWI diagnosis, severity of SWI based on criteria for mediastinitis as defined by
the Centers for Disease Control (CDC), antibiotic therapy, RD management and
patient's outcome. RESULTS: 160 patients developed SWI, 102 (64%) fulfilled CDC
criteria (CDC+) and 58 (36%) did not (CDC- SWI). Initial antibiotic treatment and
surgical management were similar in CDC+ and CDC- SWI. Patients with CDC+ SWI had
a longer duration of antibiotic therapy and a mortality rate of 17% as compared
to 3% in patients with CDC- SWI (p = 0.025). Rates of superinfection (10% and 9%)
and need for second reoperation (12% and 17%) were similar. Failure (death or
need for another reoperation) was associated with female gender, higher EuroScore
for prediction of operative mortality, and stay in the ICU. CONCLUSION: In
patients with SWI, initial one-stage surgical debridement with CDRD is associated
with favorable outcomes. CDC+ and CDC- SWI received essentially the same
management, but CDC+ SWI has a more severe outcome.
PMID- 26422146
TI - Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit
Hyperactivity Disorder.
AB - It is unclear whether attention deficit hyperactive disorder (ADHD) is a
hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest
either hyperactive or hypoactive dopamine system. Since indirect methods used in
earlier studies have arrived at contradictory conclusions, we directly measured
the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in
ADHD and healthy control volunteers was measured and compared using dynamic
molecular imaging technique. The phasic release during performance of Eriksen's
flanker task was measured in the two groups using single scan dynamic molecular
imaging technique. In these experiments volunteers were positioned in a positron
emission tomography (PET) camera and administered a dopamine receptor ligand
(11)C-raclopride intravenously. After the injection PET data were acquired
dynamically while volunteers either stayed still (tonic release experiments) or
performed the flanker task (phasic release experiments). PET data were analyzed
to measure dynamic changes in ligand binding potential (BP) and other receptor
kinetic parameters. The analysis revealed that at rest the ligand BP was
significantly higher in the right caudate of ADHD volunteers suggesting reduced
tonic release. During task performance significantly lower ligand BP was observed
in the same area, indicating increased phasic release. In ADHD tonic release of
dopamine is attenuated and the phasic release is enhanced in the right caudate.
By characterizing the nature of dysregulated dopamine neurotransmission in ADHD,
the results explain earlier findings of reduced or increased dopaminergic
activity.
PMID- 26422148
TI - Distribution and Feeding Behavior of Omorgus suberosus (Coleoptera: Trogidae) in
Lepidochelys olivacea Turtle Nests.
AB - Omorgus suberosus (Fabricius, 1775) has been identified as a potential predator
of the eggs of the turtle Lepidochelys olivacea (Eschscholtz, 1829) on one of the
main turtle nesting beaches in the world, La Escobilla in Oaxaca, Mexico. This
study presents an analysis of the spatio-temporal distribution of the beetle on
this beach (in areas of high and low density of L. olivacea nests over two
arrival seasons) and an evaluation, under laboratory conditions, of the
probability of damage to the turtle eggs by this beetle. O. suberosus adults and
larvae exhibited an aggregated pattern at both turtle nest densities; however,
aggregation was greater in areas of low nest density, where we found the highest
proportion of damaged eggs. Also, there were fluctuations in the temporal
distribution of the adult beetles following the arrival of the turtles on the
beach. Under laboratory conditions, the beetles quickly damaged both dead eggs
and a mixture of live and dead eggs, but were found to consume live eggs more
slowly. This suggests that O. suberosus may be recycling organic material;
however, its consumption of live eggs may be sufficient in some cases to
interrupt the incubation period of the turtle. We intend to apply these results
when making decisions regarding the L. olivacea nests on La Escobilla Beach, one
of the most important sites for the conservation of this species.
PMID- 26422147
TI - Rice-Infecting Pseudomonas Genomes Are Highly Accessorized and Harbor Multiple
Putative Virulence Mechanisms to Cause Sheath Brown Rot.
AB - Sheath rot complex and seed discoloration in rice involve a number of pathogenic
bacteria that cannot be associated with distinctive symptoms. These pathogens can
easily travel on asymptomatic seeds and therefore represent a threat to rice
cropping systems. Among the rice-infecting Pseudomonas, P. fuscovaginae has been
associated with sheath brown rot disease in several rice growing areas around the
world. The appearance of a similar Pseudomonas population, which here we named P.
fuscovaginae-like, represents a perfect opportunity to understand common genomic
features that can explain the infection mechanism in rice. We showed that the
novel population is indeed closely related to P. fuscovaginae. A comparative
genomics approach on eight rice-infecting Pseudomonas revealed heterogeneous
genomes and a high number of strain-specific genes. The genomes of P.
fuscovaginae-like harbor four secretion systems (Type I, II, III, and VI) and
other important pathogenicity machinery that could probably facilitate rice
colonization. We identified 123 core secreted proteins, most of which have strong
signatures of positive selection suggesting functional adaptation. Transcript
accumulation of putative pathogenicity-related genes during rice colonization
revealed a concerted virulence mechanism. The study suggests that rice-infecting
Pseudomonas causing sheath brown rot are intrinsically diverse and maintain a
variable set of metabolic capabilities as a potential strategy to occupy a range
of environments.
PMID- 26422149
TI - SIXTEEN YEARS OF PITYRIASIS VERSICOLOR IN METROPOLITAN AREA OF PORTO ALEGRE,
SOUTHERN BRAZIL.
AB - Pityriasis versicolor is the most common of the diseases caused by Malassezia
yeasts. The aim of this study is to determine the prevalence of pityriasis
versicolor and its etiological aspects in the metropolitan area of Porto Alegre,
Brazil. A retrospective cross-sectional study with data from patients of a
reference hospital from 1996 to 2011 was performed. Collected data included:
date, age, gender, ethnicity, anatomical region of lesion and the direct
mycological examination results. Among the positive results in the direct
mycological examination, 5.8% (2,239) were positive for pityriasis versicolor.
The angular coefficient (B) was -0.3%/year, showing a decrease over the years.
The disease was more prevalent in men (7.1% of men versus 5.1% of women that
underwent the direct mycological examination); younger age (median 31 years old);
"pardo" and black people (3.7% more than expected in the sample); trunk (73.44%
of the affected anatomic sites). Lesions in rare sites (groin, genitals, legs,
feet and hands) were also observed in this study. In conclusion, due to the
decrease in the prevalence of pityriasis versicolor, long-term epidemiological
studies in the metropolitan area of Porto Alegre, Brazil, are needed to continue
the monitoring of this disease.
PMID- 26422150
TI - COMPARISON BETWEEN FOUR USUAL METHODS OF IDENTIFICATION OF Candida SPECIES.
AB - Infection by Candida spp. is associated with high mortality rates, especially
when treatment is not appropriate and/or not immediate. Therefore, it is
necessary to correctly identify the genus and species of Candida. The aim of this
study was to compare the identification of 89 samples of Candida spp. by the
manual methods germ tube test, auxanogram and chromogenic medium in relation to
the ID 32C automated method. The concordances between the methods in ascending
order, measured by the Kappa index were: ID 32C with CHROMagar Candida(kappa =
0.38), ID 32C with auxanogram (kappa = 0.59) and ID 32C with germ tube (kappa =
0.9). One of the species identified in this study was C. tropicalis,which
demonstrated a sensitivity of 46.2%, a specificity of 95.2%, PPV of 80%, NPV of
81.1%, and an accuracy of 80.9% in tests performed with CHROMagar Candida;and a
sensitivity of 76.9%, a specificity of 96.8%, PPV of 90.9%, NPV of 91%, and an
accuracy of 91% in the auxanogram tests. Therefore, it is necessary to know the
advantages and limitations of methods to choose the best combination between them
for a fast and correct identification of Candida species.
PMID- 26422151
TI - Sporothrix schenckii COMPLEX:SUSCEPTIBILITIES TO COMBINED ANTIFUNGAL AGENTS AND
CHARACTERIZATION OF ENZYMATIC PROFILES.
AB - Sporothrix schenckii was reclassified as a complex encompassing six cryptic
species, which calls for the reassessment of clinical and epidemiological data of
these new species. We evaluated the susceptibility of Sporothrix albicans(n = 1)
, S. brasiliensis(n = 6) , S. globosa(n = 1), S. mexicana(n = 1) and S.
schenckii(n = 36) to terbinafine (TRB) alone and in combination with itraconazole
(ITZ), ketoconazole (KTZ), and voriconazole (VRZ) by a checkerboard microdilution
method and determined the enzymatic profile of these species with the API-ZYM
kit. Most interactions were additive (27.5%, 32.5% and 5%) or indifferent (70%,
50% and 52.5%) for TRB+KTZ, TRB+ITZ and TRB+VRZ, respectively. Antagonisms were
observed in 42.5% of isolates for the TRB+VRZ combination. Based on enzymatic
profiling, the Sporothrix schenckii strains were categorized into 14 biotypes.
Leucine arylamidase (LA) activity was observed only for S. albicans and S.
mexicana. The species S. globosa and S. Mexicana were the only species without
beta-glucosidase (GS) activity. Our results may contribute to a better
understanding of virulence and resistance among species of the genus Sporothrix
in further studies.
PMID- 26422152
TI - ISOLATION OF Cryptococcus neoformans FROM ENVIRONMENTAL SAMPLES COLLECTED IN
SOUTHEASTERN NIGERIA.
AB - Cryptococcosis caused by Cryptococcus neoformans is the second most common fungal
opportunistic pathogen and a life-threatening infection with serious clinical
manifestations especially in HIV/AIDS and other immunocompromised patients. In
Nigeria, HIV/AIDS infection has reached an alarming level. Despite this,
information on the presence of this fungus in clinical and environmental samples
is very scanty in Nigeria and many other parts of Africa. We set out to evaluate
the presence of Cryptococcus neoformans or C. gattiiin pigeon droppings obtained
from Southeastern Nigeria. One hundred and seventy-seven samples of pigeon
droppings from six sample types were collected. The area covered comprised of ten
cities and other locations spanning across five States in Nigeria. Using
established techniques, Cryptococcus neoformans was isolated from 39 of the 177
(22.0%) samples overall. No C. gattiiwas isolated. Most of the isolates (32.4%)
were recovered from dovecotes (11 of 34) followed closely by samples taken from
markets (31.8%; seven of 22) and least from the church (4.0%; one of 25). The
highest isolation rate (38.9%) was found in samples from Enugu-Ezike(seven of 23)
while the least came from Afikpo and the other locations each with 9.1% isolation
rate. This is the first large-scale screening of Cryptococcus neoformans from
pigeon droppings in Nigeria. The ecological and epidemiological significance of
these findings are discussed.
PMID- 26422153
TI - QUANTITATIVE VS. CONVENTIONAL PCR FOR DETECTION OF HUMAN ADENOVIRUSES IN WATER
AND SEDIMENT SAMPLES.
AB - Human Adenoviruses (HAdV) are notably resistant in the environment. These agents
may serve as effective indicators of fecal contamination, and may act as
causative agents of a number of different diseases in human beings. Conventional
polymerase chain reaction (PCR) and, more recently, quantitative PCR (qPCR) are
widely used for detection of viral agents in environmental matrices. In the
present study PCR and SYBR(r)Green qPCR assays were compared for detection of
HAdV in water (55) and sediments (20) samples of spring and artesian wells, ponds
and streams, collected from dairy farms. By the quantitative methodology HAdV
were detected in 87.3% of the water samples and 80% of the sediments, while by
the conventional PCR 47.3% and 35% were detected in water samples and sediments,
respectively.
PMID- 26422154
TI - ROTAVIRUS GENOTYPES CIRCULATING IN BRAZIL, 2007-2012: IMPLICATIONS FOR THE
VACCINE PROGRAM.
AB - Regarding public health in Brazil, a new scenario emerged with the establishment
of universal rotavirus (RV) vaccination programs. Herein, the data from the five
years of surveillance (2007-2012) of G- and P-type RV strains isolated from
individuals with acute gastroenteritis in Brazil are reported. A total of 6,196
fecal specimens were investigated by ELISA and RT-PCR. RVs were detected in 19.1%
(1,181/6,196). The peak of RV incidence moved from June-August to September. RV
was detected less frequently (19.5%) among children <= 5 years than in older
children and adolescents (6-18 years) (40.6%). Genotype distribution showed a
different profile for each year: G2P[4] strains were most prevalent during 2007
2010, G9P[8] in 2011, and G12P[8] in 2012. Mixed infections (G1+G2P[4],
G2+G3P[4]+P[8], G2+G12P[8]), unusual combinations (G1P[4], G2P[6]), and rare
strains (G3P[3]) were also identified throughout the study period. Widespread
vaccination may alter the RV seasonal pattern. The finding of RV disease
affecting older children and adolescents after vaccine implementation has been
reported worldwide. G2P[4] emergence most likely follows a global trend seemingly
unrelated to vaccination, and G12, apparently, is emerging in the Brazilian
population. The rapidly changing RV genotype patterns detected during this study
illustrate a dynamic population of co-circulating wildtype RVs in Brazil.
PMID- 26422155
TI - SERUM LEVELS OF COPPER AND IRON IN DENGUE FEVER.
AB - The role of trace elements in dengue virulence is not yet known. The present
study assessed the serum levels of two micronutrients, copper and iron, in cases
of dengue fever. The study involved 96 patients of whom 48 had either severe or
non-severe forms of dengue (with and without warning signs), and the remaining 48
were patients with other febrile illnesses (OFI), used as controls. Serum levels
of copper and iron were evaluated at admission and by the time of defervescence
using commercially available kits. At admission, no difference in the level of
serum copper was observed between cases and controls. In the group of dengue
cases, the copper level was found to be significantly decreased in severe and non
severe cases with warning signs, compared to non-severe cases without warning
signs. In contrast, by the time of defervescence the copper level was found to be
increased in all dengue cases compared to OFI controls, but no difference was
observed among dengue cases. Unlike OFI controls, dengue cases showed an
increasing pattern of copper levels from admission until defervescence. On the
other hand, no such significant differences were observed in the serum level of
iron in the clinical groups, except for a decreased iron level found in severe
cases, compared to non-severe dengue without warning signs. The results show that
copper is associated with dengue severity and this finding emphasizes the need to
investigate the involvement of trace elements in disease severity so as to
improve the prognosis of dengue.
PMID- 26422156
TI - IDENTIFICATION OF SANDFLIES (Diptera: Psychodidae: Phlebotominae) BLOOD MEALS IN
AN ENDEMIC LEISHMANIASIS AREA IN BRAZIL.
AB - The aim of this study was to identify blood meals of female sandflies captured in
the municipality of Governador Valadares, an endemic area of visceral and
cutaneous leishmaniasis, in the State of Minas Gerais, Brazil. From May 2011 to
January 2012, captures were performed using HP light traps in four districts.
There were 2,614 specimens (2,090 males and 524 females) captured; 97 engorged
females were identified belonging to the species Lutzomyia longipalpis(82.1%) and
Lutzomyia cortelezzii(17.9%). Considering simple and mixed feeding, the enzyme
linked immunosorbent assay revealed a predominance of chicken blood (43.6%) in
Lutzomyia longipalpis, showing the important role that chickens exert around the
residential areas of Governador Valadares. This finding increases the chances of
sandflies contact with other vertebrates and consequently the risk of
leishmaniasis transmission.
PMID- 26422158
TI - WATER FROM DIFFERENT SOURCES USED FOR THE IRRIGATION OF VEGETABLES TO BE
MARKETED: RESEARCH ON Cryptosporidium spp., Giardia spp., AND COLIFORMS IN
PARANA, BRAZIL.
AB - The aim of this work was to compare, from a parasitological ( Cryptosporidium
spp. and Giardia duodenalis), bacteriological (total and thermotolerants
coliforms) and physicochemical perspective, water sources used for drinking and
irrigation of vegetables intended to be sold for human consumption. From January
2010 to May 2011, samples of different water sources from vegetable producing
properties were collected; 100 liters for parasitological analysis, 200 mL for
bacteriological analysis, and five liters for physicochemical analysis. Water
samples were filtered under vacuum with a kit containing a cellulose acetate
membrane filter, 1.2 um (Millipore(r), Barueri, SP, Brazil). The material
retained on the membrane was mechanically extracted and analyzed by direct
immunofluorescence (Merifluor(r)kit). From 20 rural properties investigated, 10
had artesian wells (40 samples), 10 had common wells (40 samples), and one had a
mine (four samples), the latter contaminated by Cryptosporidium spp. In samples
from artesian wells, 90 to 130 meters depth, 42.5% were positive for total
coliforms and 5.0% were identified to have abnormal coloration. From the samples
of common wells, 14 to 37 meters depth, 87.5% were contaminated with total
coliforms, 82.5% were positive for thermotolerant coliforms, and 12.5% had color
abnormalities. We did not detect the presence of Giardia spp. or Cryptosporidium
spp. in artesian and common wells. The use of artesian or common wells is an
important step in the control of the spreading of zoonoses, particularly
Cryptosporidium spp. and Giardia spp., as well as artesian wells for coliform
control in local production of vegetables to be marketed.
PMID- 26422157
TI - CANINE VISCERAL LEISHMANIASIS CASE INVESTIGATION IN THE JACARE REGION OF NITEROI,
RIO DE JANEIRO, BRAZIL.
AB - American visceral leishmaniasis is a vector-borne zoonosis in expansion in
Brazil. Dogs are the main urban reservoir. Departing from a case of canine
visceral leishmaniasis (CVL) in Jacare, Niteroi, Rio de Janeiro State, an
epidemiological canine and entomological study was performed to assess the
extension of the disease at the location. Sample was collected around the case
and the dogs identified by serological tests (rapid double platform
immunochromatographic exams, immunoenzymatic assay/ELISA, indirect
immunofluorescence/IFAT). The parasitological diagnosis was performed in animals
positive in at least one of these tests. The entomological study was carried out
by using light traps and manual collection. The associations between canine
variables and outcome (ELISA and IFAT reagents) were assessed by the chi-square
test and adjusted by multivariate logistic regression for those associations with
p < 0.1 in the bivariate analysis. Seventeen cases of CVL were detected among 110
evaluated dogs (prevalence of 15.5%). Presence of ectoparasites (OR 6.5; 95% CI
1.1-37.4), animals with clinical signs (OR 9.5; 95% CI 1.2-76.6), and previous
cases of CVL in the same house (OR 17.9; 95% CI 2.2-147.1) were associated with
the outcome. Lutzomyia longipalpis was not detected. Our results are indicative
of an ongoing transmission in the area.
PMID- 26422159
TI - EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL
IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE.
AB - The efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an
experimental murine model and results were compared to those obtained using
mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided
into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T.
canis and grouped as follows, G I: infected untreated mice; G II: infected mice
treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice
treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60
dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising
uninfected mice. Mice were bled via retro-orbital plexus on four occasions
between 30 and 120 dpi. Sera were processed using the ELISA technique to detect
IgG anti- Toxocara antibodies. At 120 dpi, mice were sacrificed for larval
recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed
similar levels of anti- Toxocara IgG antibodies among mice infected but not
submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval
recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ
showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load
compared with NTZ, which showed only 46.5% reduction. We conclude that
administration of these anthelmintics did not modify the humoral response in
experimental infection by T. canis. No parasitological cure was observed with
either drug; however, a greater reduction in parasite load was achieved following
treatment with MBZ.
PMID- 26422160
TI - MOLECULAR CHARACTERIZATION OF AMERICAN CUTANEOUS LEISHMANIASIS IN THE TRI-BORDER
AREA OF ASSIS BRASIL, ACRE STATE, BRAZIL.
AB - In this study, Leishmania species were identified by Polymerase Chain Reaction
(PCR). The epidemiology of patients suspected of having American Cutaneous
Leishmaniasis in the municipality of Assis Brasil, Acre State, located in the
Brazil/Peru/Bolivia tri-border was also investigated. By PCR, the DNA of
Leishmania was detected in 100% of the cases (37 samples) and a PCR-Restriction
Fragment Length Polymorphism (RFLP) of the hsp 70 gene identified the species in
32 samples: Leishmania (Viannia) braziliensis (65.6%) , L. (V.) shawi (28.1%) ,
L. (V.) guyanensis (3.1%) and mixed infection L. (V.) guyanensis and L.
(Leishmania) amazonensis(3.1%)This is the first report of L. (V.) shawi and L.
(L.) amazonensis in Acre. The two predominant species were found in patients
living in urban and rural areas. Most cases were found in males living in rural
areas for at least three years and involved in rural work. This suggests, in most
cases, a possible transmission of the disease from a rural/forest source,
although some patients had not engaged in activities associated with permanence
in forestall areas, which indicate a possible sandflies adaptation to the
periurban setting.
PMID- 26422161
TI - DIARRHEA OUTBREAK IN PERNAMBUCO, BRAZIL, ASSOCIATED WITH A HEAT-STABLE CYTOTOXIC
ENTEROTOXIN PRODUCED BY Aeromonas caviae.
AB - In the present study enterotoxic and cytotoxic activities of twenty Aeromonas
caviae strains were examined. They originated from fecal specimens of patients
with acute diarrhea during an outbreak in Brazil in 2004. Culture supernatants of
fourteen strains (70%) caused fluid accumulation in rabbit ileal intestinal loops
and in suckling mice assays, and also showed a cytotoxic activity in Vero and
Caco-2 cells. The enterotoxic and cytotoxic factors were heat-stable after
culture supernatants treatment at 100 oC. The results revealed that A. caviae
strains produce a putative diarrheagenic virulence factor, a heat-stable
cytotoxic enterotoxin that could be linked to the diarrhea outbreak that took
place in Brazil.
PMID- 26422163
TI - PROBABLE RECOGNITION OF HUMAN ANISAKIASIS IN BRAZIL?
PMID- 26422164
TI - KPC-PRODUCING Serratia marcescens IN A HOME-CARE PATIENT FROM RECIFE, BRAZIL.
AB - In this brief communication we describe the occurrence of a KPC-producing
Serratia marcescens isolate in a home-care patient from Recife, Brazil. The
blaKPC, blaSPM, blaIMP, blaVIM, blaOXA, blaCTX-M, blaSHV, blaTEM and blaGES genes
were investigated by Polymerase Chain Reaction (PCR) and DNA sequencing. The
isolate was positive for blaKPC-2 and blaTEM-1 and was resistant to aztreonam,
cefepime, cefotaxime, imipenem, meropenem, gentamicin, ciprofloxacin and
cefazidime, and susceptible only to amikacin, tigecycline and gatifloxacin. This
is the first report in Brazil of KPC-producing S. marcescens clinical isolate
outside of a hospital environment. Caregivers should be alert for the presence of
this isolate in the community setting.
PMID- 26422162
TI - MOLECULAR INVESTIGATION OF HEMOTROPIC MYCOPLASMAS IN HUMAN BEINGS, DOGS AND
HORSES IN A RURAL SETTLEMENT IN SOUTHERN BRAZIL.
AB - The aims of this study were to determine the prevalence of hemoplasmas in a rural
Brazilian settlement's population of human beings, their dogs and horses, highly
exposed to tick bites; to identify the tick species parasitizing dogs and horses,
and analyze factors associated with their infection. Blood samples from 132 dogs,
16 horses and 100 humans were screened using a pan-hemoplasma SYBR green real
time PCR assay followed by a species-specific TaqMan real-time PCR. A total of
59/132 (44.7%) dog samples were positive for hemoplasmas (21 Mycoplasma
haemocanis alone, 12 ' Candidatus Mycoplasma haematoparvum' alone and 21 both).
Only 1/100 (1.0%) human sample was positive by qPCR SYBR green, with no
successful amplification of 16S rRNA or 23 rRNA genes despite multiple attempts.
All horse samples were negative. Dogs >1 year of age were more likely to be
positive for hemoplasmas ( p= 0.0014). In conclusion, although canine hemoplasma
infection was highly prevalent, cross-species hemoplasma transmission was not
observed, and therefore may not frequently occur despite overexposure of agents
and vectors.
PMID- 26422165
TI - FIRST REPORT OF ACUTE CHAGAS DISEASE BY VECTOR TRANSMISSION IN RIO DE JANEIRO
STATE, BRAZIL.
AB - Chagas disease (CD) is an endemic anthropozoonosis from Latin America of which
the main means of transmission is the contact of skin lesions or mucosa with the
feces of triatomine bugs infected by Trypanosoma cruzi. In this article, we
describe the first acute CD case acquired by vector transmission in the Rio de
Janeiro State and confirmed by parasitological, serological and PCR tests. The
patient presented acute cardiomyopathy and pericardial effusion without cardiac
tamponade. Together with fever and malaise, a 3 cm wide erythematous, non
pruritic, papule compatible with a "chagoma" was found on his left wrist. This
case report draws attention to the possible transmission of CD by non-domiciled
native vectors in non-endemic areas. Therefore, acute CD should be included in
the diagnostic workout of febrile diseases and acute myopericarditis in Rio de
Janeiro.
PMID- 26422166
TI - FATAL DISSEMINATED CRYPTOCOCCOSIS WITH RENAL INVOLVEMENT IN AN HIV-INFECTED
PATIENT.
AB - INTRODUCTION: We present a fatal case of disseminated cryptococcosis in a young
man whose diagnosis of HIV infection was made at the time of admission to the
emergency room. CASE REPORT: The patient was a twenty-three-year-old man, with a
history of daily fever during one month associated with diarrhea, weight loss,
headache, vomiting and generalized seizures. He also had a history of diabetes
mellitus, alcoholism and drug addiction. Upon physical examination the patient
was pale, disoriented and had periods of agitation. White blood cells count was
3,440/mm3 (5% lymphocytes), hemoglobin was 10 g/dL, platelets were 83,000/ mm3.
Creatinine was 0.7 mg/dL; urea 19 mg/dL; Na, K, and liver enzymes were within
normal limits. Lactic dehydrogenase was 494 IU/L. Cerebrospinal fluid (CSF)
analysis revealed 10 white blood cells/mm3 (58% neutrophils, 31% lymphocytes, 11%
monocytes) and 2 red blood cells/mm3. India ink test revealed six Cryptococcus
yeasts/mm3. CSF glucose was 122 mg/dL and protein was 36 mg/ dL. VDRL test was
negative and anti-HIV test was positive. Intravenous hydration, insulin,
phenytoin, fluconazole, pyrimethamine, sulfadiazine, folinic acid, and
amphotericin B were started. The patient did not improve and became obtunded and
hypotensive. He was intubated and put on mechanical respiration. He received
vasoactive drugs and died less than 24 hours after admission. A postmortem
examination was performed and revealed disseminated cryptococcosis, with severe
involvement of the kidneys. CONCLUSION: Cryptococcosis, as a rule, is a systemic
disease that affects mostly immunocompromised individuals, especially patients
with AIDS. When diagnosed late in its course it has a very high mortality.
PMID- 26422167
TI - EMPHYSEMATOUS PYELONEPHRITIS.
PMID- 26422169
TI - A Practical Diabatisation Scheme for Use with the Direct-Dynamics Variational
Multi-Configuration Gaussian Method.
AB - A method for diabatising multiple electronic states on-the-fly within the direct
dynamics variational multi-configuration Gaussian method for calculating quantum
nuclear dynamics is presented. The method is based upon the propagation of the
adiabatic-diabatic transformation matrix along the paths followed by the Gaussian
basis functions that constitute the nuclear wave function, by use of a well-known
differential equation relating the matrix and the nonadiabatic vector coupling
terms between the electronic states. The implementation of the method is
described, and test calculations are presented using the ground and first-excited
states of the butatriene cation as an example, allowing comparison to the earlier
regularisation diabatisation scheme as well as to full nuclear dynamics on a
precomputed potential energy surface. The new scheme is termed propagation
diabatisation.
PMID- 26422168
TI - Linkage-specific conformational ensembles of non-canonical polyubiquitin chains.
AB - Polyubiquitination is a critical protein post-translational modification involved
in a variety of processes in eukaryotic cells. The molecular basis for selective
recognition of the polyubiquitin signals by cellular receptors is determined by
the conformations polyubiquitin chains adopt; this has been demonstrated for K48-
and K63-linked chains. Recent studies of the so-called non-canonical chains
(linked via K6, K11, K27, K29, or K33) suggest they play important regulatory
roles in growth, development, and immune system pathways, but biophysical studies
are needed to elucidate the physical/structural basis of their interactions with
receptors. A first step towards this goal is characterization of the
conformations these chains adopt in solution. We assembled diubiquitins (Ub2)
comprised of every lysine linkage. Using solution NMR measurements, small-angle
neutron scattering (SANS), and in silico ensemble generation, we determined
population-weighted conformational ensembles that shed light on the structure and
dynamics of the non-canonical polyubiquitin chains. We found that polyubiquitin
is conformationally heterogeneous, and each chain type exhibits unique
conformational ensembles. For example, K6-Ub2 and K11-Ub2 (at physiological salt
concentration) are in dynamic equilibrium between at least two conformers, where
one exhibits a unique Ub/Ub interface, distinct from that observed in K48-Ub2 but
similar to crystal structures of these chains. Conformers for K29-Ub2 and K33-Ub2
resemble recent crystal structures in the ligand-bound state. Remarkably, a
number of diubiquitins adopt conformers similar to K48-Ub2 or K63-Ub2, suggesting
potential overlap of biological function among different lysine linkages. These
studies highlight the potential power of determining function from elucidation of
conformational states.
PMID- 26422170
TI - Dynamics of Electrically Modulated Colloidal Droplet Transport.
AB - Electrically actuated transport dynamics of colloidal droplets, on a hydrophobic
dielectric film covering an array of electrodes, is studied here. Specifically,
the effects of the size and electrical properties (zeta-potential) of the
colloidal particles on such transport characteristics are investigated. For the
colloidal droplets, the application of an electrical voltage leads to additional
attenuation of the local dielectric-droplet interfacial tension. This is due to
the electrically triggered enhanced colloidal particle adsorption at the
dielectric-droplet interface, in the immediate vicinity of the droplet three
phase contact line (TPCL). The extent of such interfacial particle adsorption,
and hence, the extent of the consequential reduction in the interfacial tension,
is dictated by the combined effects of the three-phase contact line spreading,
particle size, the interfacial electrostatic interaction between the colloidal
particles (if charged) and the charged dielectric surface above the activated
electrode, and the interparticle electrostatic repulsion. The electrical driving
force of varying magnitude, stemming from this altered solid-liquid interfacial
tension gradient in the presence of the colloidal particles, culminates in
different droplet transport velocity and droplet transfer frequency for different
colloidal droplets. We substantiate the inferences from our experimental results
by a quasi-steady state force balance model for colloidal droplet transport. We
believe that the present work will provide an accurate framework for determining
the optimal design and operational parameters for digital microfluidic chips
handling colloidal droplets, as encountered in a plethora of applications.
PMID- 26422171
TI - Effect of Media Usage Selection on Social Mobilization Speed: Facebook vs E-Mail.
AB - Social mobilization is a process that enlists a large number of people to achieve
a goal within a limited time, especially through the use of social media. There
is increasing interest in understanding the factors that affect the speed of
social mobilization. Based on the Langley Knights competition data set, we
analyzed the differences in mobilization speed between users of Facebook and e
mail. We include other factors that may influence mobilization speed (gender,
age, timing, and homophily of information source) in our model as control
variables in order to isolate the effect of such factors. We show that, in this
experiment, although more people used e-mail to recruit, the mobilization speed
of Facebook users was faster than that of those that used e-mail. We were also
able to measure and show that the mobilization speed for Facebook users was on
average seven times faster compared to e-mail before controlling for other
factors. After controlling for other factors, we show that Facebook users were
1.84 times more likely to register compared to e-mail users in the next period if
they have not done so at any point in time. This finding could provide useful
insights for future social mobilization efforts.
PMID- 26422172
TI - Indocyanine Green Lymphography Findings in Limb Lymphedema.
AB - BACKGROUND AND METHODS: Indocyanine green (ICG) lymphography is one of several
methods of lymphography to detect lymphatic channels and evaluate patients
clinically with limb lymphedema. ICG imaging is made possible by the use of a
near-infrared camera device. The fluorescence images were digitalized for real
time display. RESULTS: ICG lymphography findings are largely classifiable into
two patterns: normal linear pattern and abnormal dermal backflow (DB) pattern.
ICG lymphography pattern changes from the normal linear pattern to abnormal DB
patterns in obstructive peripheral lymphedema; with progression of lymphedema, DB
patterns change from splash pattern, to stardust pattern, and finally to diffuse
pattern. We classify ICG lymphography progression into 0 to V stages for the
upper extremity, the lower extremity and into 0 to IV stages for the genital
area. CONCLUSION: In DB stage II, most patients are symptomatic; thus, aggressive
treatments, such as lymphaticovenular anastomosis, are indicated. In DB stages
III to V, lymphaticovenular anastomosis is recommended because most patients are
refractory to conservative therapies.
PMID- 26422173
TI - The V-Plasty: A Novel Microsurgical Technique for Anastomosis of Vessels with
Marked Size Discrepancy.
AB - BACKGROUND: The art of reconstructive microsurgery is still progressing after
Carrel's original description of "vascular repair" in 1902. Reports of the
successful repair of vessels smaller than 1 mm in diameter are currently
commonplace. However, the technique of microvascular anastomosis to connect
vessels with large diameter discrepancy, greater than 1 mm, has not yet been
perfected. This article reports a novel option to anastomose two vessels of
different sizes by adapting the diameters of the two stumps and creating a gentle
slope that dramatically reduces turbulences in the blood stream. METHODS: The "V
plasty" consists in designing a v-shaped flap on the wall of the large vessel and
a longitudinal incision on the small one. The V-flap is then introduced into the
V-defect of the small vessel, creating a smooth transition of the diameters
between the two vessels. Mathematical calculation of the dimensions of the V-flap
was conducted with different ratios' discrepancies of the two vessels ranging
from 1.5 to 4. Clinically, 14 microvascular V-plasty were performed in 8
patients. RESULTS: The theoretical simulation and our clinical experience of 14
cases allowed us to propose the different dimensions (length and width) of the V
plasty according to the ratio of vessels discrepancies. CONCLUSION: The V-plasty
microanastomosis is an alternative method to attach vessels with size
discrepancy. It simply equalizes the donor and recipient vessels' diameters. Its
main advantage is to maintain a linear axis between the two vessels whatever the
discrepancy ratio is.
PMID- 26422174
TI - Effect of Vascular Endothelial Growth Factor Administration on Nerve Regeneration
after Autologous Nerve Grafting.
AB - BACKGROUND: The aim of this study was to evaluate the effect of vascular
endothelial growth factor (VEGF) administration around the autologous nerve graft
on nerve recovery in a rat model. METHODS: A total of 69 rats were randomly
divided into three experimental groups. A 10-mm sciatic nerve defect was made and
reconstructed with the reversed nerve segment. Group I received an osmotic pump
with saline, group II received an osmotic pump with VEGF, and group III added a
silicone tube around the nerve graft to decrease the surrounding blood supply.
Nine animals in each group were sacrificed on day 3 to evaluate improvement in
new vessel formation. In each group 14 animals were sacrificed at 16 weeks after
the initial procedure to evaluate the functional motor nerve regeneration using
compound muscle action potential, isometric tetanic force, wet muscle weight, and
nerve histomorphometry. RESULTS: The average vascular density on day 3 was 10.7%
in group I, 21.4% in group II, and 0.9% in group III. These differences were
significant. However, the average maximum isometric tetanic force at 16 weeks was
54.4% in group I, 57.5% in group II, and 47.6% in group III. No difference was
found with or without VEGF administration. Histomorphometric analysis was also
not significantly different between the groups. CONCLUSIONS: New vessel formation
on autologous nerve graft was enhanced by VEGF administration. However, the
neovascularization effect of VEGF administration did not translate into better
motor nerve recovery.
PMID- 26422175
TI - Use of Model for End-Stage Liver Disease Scoring Dynamics in Critically Ill
Cirrhotic Trauma Patients.
PMID- 26422176
TI - Analysis of heavy metals from water, sediment, and tissues of Labeo angra
(Hamilton, 1822), from an Ox-box lake- an wetland site from Assam, India.
AB - The aim of this study was to assess the regional impacts of heavy metals (Mn, Fe,
Mg, Ca, Cu, Zn, Cd, Cr, Pb and Ni) on water, sediment and a native, teleost fish
species, Labeo angra, inhabiting a flood plain wetland of Barak River in Assam,
India. Heavy metal concentrations in the water, sediments and fish were measured;
bioaccumulation factor, metal pollution index as well as condition indices were
calculated, to assess the pollution load and health status of the fish.
Multivariate statistical analysis was used on wetland water and sediment heavy
metals to ascertain the possible sources and seasonal variations of the
pollutants. Results showed that most heavy metals in the wetland water and
sediments exceeded the water (drinking and irrigation) and sediment quality
guidelines, respectively. Seasonal variations were observed for geogenic heavy
metals, Mn, Fe, Mg and Ca while no seasonal variations were observed for
anthropogenic heavy metals, Cu, Cd, Cr, Pb and Ni. Multivariate statistical
analysis showed that there was strong correlation between geogenic and
anthropogenic heavy metals in water and sediment, both originating from the
common anthropogenic sources. Accumulation of most of the metals in all the
tissues was above the safe limits as recommended by the Food and Agriculture
Organization. High bioaccumulation factors and metal pollution index for these
metals in the different tissues revealed that metals were extensively bio
accumulated and bioconcentrated. Condition indices in fish from the wetland
suggested metabolic abnormalities.
PMID- 26422177
TI - Region specific optimization of continuous linear attenuation coefficients based
on UTE (RESOLUTE): application to PET/MR brain imaging.
AB - The reconstruction of PET brain data in a PET/MR hybrid scanner is challenging in
the absence of transmission sources, where MR images are used for MR-based
attenuation correction (MR-AC). The main challenge of MR-AC is to separate bone
and air, as neither have a signal in traditional MR images, and to assign the
correct linear attenuation coefficient to bone. The ultra-short echo time (UTE)
MR sequence was proposed as a basis for MR-AC as this sequence shows a small
signal in bone. The purpose of this study was to develop a new clinically
feasible MR-AC method with patient specific continuous-valued linear attenuation
coefficients in bone that provides accurate reconstructed PET image data. A total
of 164 [(18)F]FDG PET/MR patients were included in this study, of which 10 were
used for training. MR-AC was based on either standard CT (reference), UTE or our
method (RESOLUTE). The reconstructed PET images were evaluated in the whole
brain, as well as regionally in the brain using a ROI-based analysis. Our method
segments air, brain, cerebral spinal fluid, and soft tissue voxels on the
unprocessed UTE TE images, and uses a mapping of R(*)2 values to CT Hounsfield
Units (HU) to measure the density in bone voxels. The average error of our method
in the brain was 0.1% and less than 1.2% in any region of the brain. On average
95% of the brain was within +/-10% of PETCT, compared to 72% when using UTE. The
proposed method is clinically feasible, reducing both the global and local errors
on the reconstructed PET images, as well as limiting the number and extent of the
outliers.
PMID- 26422178
TI - High Trap Formation and Low Metabolite Production by Disruption of the Polyketide
Synthase Gene Involved in the Biosynthesis of Arthrosporols from Nematode
Trapping Fungus Arthrobotrys oligospora.
AB - A group of morphology regulatory arthrosporol metabolites have been recently
characterized from carnivorous fungus Arthrobotrys oligospora that can develop
trapping networks to capture their prey. A combination of genetic manipulation
and chemical analyses was applied to characterize the function of one polyketide
synthase (PKS) gene AOL_s00215g283 in A. oligospora, which was putatively
involved in the production of 6-methylsalicylic acid. High-performance liquid
chromatography analysis showed that the disruption of the PKS gene not only led
to the total loss of the arthrosporol A but also resulted in significant
reduction in the production of secondary metabolites in the cultural broth of the
mutant DeltaAOL_s00215g283 strain. Interestingly, the mutant strain displayed
significant increases in the trap formation and the nematicidal activity by 10
and 2 times, respectively, higher than the wild-type strain. These findings
revealed a pathogenicity-related biosynthetic gene of this agriculturally
important biological agent and have implications for establishment of efficient
fungal biocontrol agents.
PMID- 26422179
TI - Mechanism and Mitigation of the Decomposition of an Oxorhenium Complex-Based
Heterogeneous Catalyst for Perchlorate Reduction in Water.
AB - A biomimetic heterogeneous catalyst combining palladium nanoparticles and an
organic ligand-coordinated oxorhenium complex on activated carbon, Re(hoz)2-Pd/C,
was previously developed and shown to reduce aqueous perchlorate (ClO4-) with H2
at a rate ~100 times faster than the first generation ReOx-Pd/C catalyst prepared
from perrhenate (ReO4-). However, the immobilized Re(hoz)2 complex was shown to
partially decompose and leach into water as ReO4-, leading to an irreversible
loss of catalytic activity. In this work, the stability of the immobilized
Re(hoz)2 complex is shown to depend on kinetic competition between three
processes: (1) ReV(hoz)2 oxidation by ClO4- and its reduction intermediates ClOx
, (2) ReVII(hoz)2 reduction by Pd-activated hydrogen, and (3) hydrolytic
ReVII(hoz)2 decomposition. When ReV(hoz)2 oxidation is faster than ReVII(hoz)2
reduction, the ReVII(hoz)2 concentration builds up and leads to hydrolytic
decomposition to ReO4- and free hoz ligand. Rapid ReV(hoz)2 oxidation is mainly
promoted by highly reactive ClOx- formed from the reduction of ClO4-. To mitigate
Re(hoz)2 decomposition and preserve catalytic activity, ruthenium (Ru) and
rhodium (Rh) were evaluated as alternative H2 activators to Pd. Rh showed
superior activity for reducing the ClO3- intermediate to Cl-, thereby preventing
ClOx- buildup and lowering Re complex decomposition in the Re(hoz)2-Rh/C
catalyst. In contrast, Ru showed the lowest ClO3- reduction activity and resulted
in the most Re(hoz)2 decomposition among the Re(hoz)2-M/C catalysts. This work
highlights the importance of using mechanistic insights from kinetic and
spectroscopic tests to rationally design water treatment catalysts for enhanced
performance and stability.
PMID- 26422180
TI - Dissemination of antibiotic resistance in methicillin-resistant Staphylococcus
aureus and vancomycin-resistant S aureus strains isolated from hospital
effluents.
AB - Vancomycin-resistant Staphylococcus aureus (VRSA) and methicillin-resistant S
aureus (MRSA) strains were examined in hospital effluents. Most S aureus strains
are resistant to methicillin (MRSA), followed by tetracycline. Approximately 15%
of MRSA strains are also resistant to vancomycin (VRSA). All VRSA strains
developed a VanR/VanS-regulated 2-component system of VanA-type resistance in
their genome. Results indicate that there is a possibility of developing
resistance to aminoglycosides by VRSA strains in the near future.
PMID- 26422181
TI - Sociocognitive determinants of self-reported compliance with standard
precautions: Development and preliminary testing of a questionnaire with French
health care workers.
AB - BACKGROUND: Inconsistent compliance of health care workers with standard
precautions has already been documented. The objective of this study was to
develop a questionnaire to investigate the sociocognitive determinants of
compliance with standard precautions based on the theory of planned behavior.
METHODS: To construct the Standard Precautions Questionnaire (SPQ), items were
selected using a systematic review of literature and semistructured interviews
with 54 health care workers. Thirty-five items were selected for a draft
questionnaire. These questionnaires were sent to 649 health care workers in 3
medical specialties (pediatrics, geriatrics, and intensive care) in a French
University hospital. A total of 331 valid questionnaires were analyzed. RESULTS:
Factor analysis yielded a final 7-factor solution with an explained variance of
66.51%, with 24 items. The 7 dimensions were the following: attitude toward
standard precautions, social influence facilitating organization, exemplary
behavior of colleagues, organizational constraints, individual constraints, and
intention to perform standard precautions. Some differences were observed between
medical specialties on attitude toward standard precautions, social influence,
and individual constraints. CONCLUSION: The SPQ met the conditions of reliability
and validity in accordance with psychometric demands and could be used to
evaluate attitudes and intention to perform standard precautions among medical
and nursing staff.
PMID- 26422182
TI - Effects of a catheter-associated urinary tract infection prevention campaign on
infection rate, catheter utilization, and health care workers' perspective at a
community safety net hospital.
AB - Preventing catheter-associated urinary tract infections is in the forefront of
health care quality. However, nurse and physician engagement is a common barrier
in infection prevention efforts. After implementation of a multidisciplinary
catheter-associated urinary tract infection (CAUTI) prevention campaign, we
studied the impact of our campaign and showed its association with reducing the
CAUTI rate and catheter utilization and the positive effect on health care
workers' engagement and perspectives. CAUTI prevention campaigns can lead to
lower infection rates and change health care workers' perspective.
PMID- 26422183
TI - Non-invasive ventilation: Has it been forgotten in the diagnosis-related groups?
PMID- 26422184
TI - Pleural empyema in a pneumonectomized patient as a complication of colonoscopy.
PMID- 26422185
TI - Pulmonary Embolism Detection with Three-dimensional Ultrashort Echo Time MR
Imaging: Experimental Study in Canines.
AB - PURPOSE: To demonstrate the feasibility of free-breathing three-dimensional (3D)
radial ultrashort echo time (UTE) magnetic resonance (MR) imaging in the
simultaneous detection of pulmonary embolism (PE) and high-quality evaluation of
lung parenchyma. MATERIALS AND METHODS: The institutional animal care committee
approved this study. A total of 12 beagles underwent MR imaging and computed
tomography (CT) before and after induction of PE with autologous clots. Breath
hold 3D MR angiography and free-breathing 3D radial UTE (1.0-mm isotropic spatial
resolution; echo time, 0.08 msec) were performed at 3 T. Two blinded radiologists
independently marked and graded all PEs on a four-point scale (1 = low
confidence, 4 = absolutely certain) on MR angiographic and UTE images. Image
quality of pulmonary arteries and lung parenchyma was scored on a four-point
scale (1 = poor, 4 = excellent). Locations and ratings of emboli were compared
with reference standard CT images by using an alternative free-response receiver
operating characteristic curve (AFROC) method. Areas under the curve and image
quality ratings were compared by using the F test and the Wilcoxon signed-rank
test. RESULTS: A total of 48 emboli were detected with CT. Both readers showed
higher sensitivity for PE detection with UTE (83% and 79%) than with MR
angiography (75% and 71%). The AFROC area under the curve was higher for UTE than
for MR angiography (0.95 vs 0.89), with a significant difference in area under
the curve of 0.06 (95% confidence interval: 0.01, 0.11; P = .018). UTE image
quality exceeded that of MR angiography for subsegmental arteries (3.5 +/- 0.7 vs
2.9 +/- 0.5, P = .002) and lung parenchyma (3.8 +/- 0.5 vs 2.2 +/- 0.2, P <
.001). The apparent signal-to-noise ratio in pulmonary arteries and lung
parenchyma was significantly higher for UTE than for MR angiography (41.0 +/- 5.2
vs 24.5 +/- 6.2 [P < .001] and 10.2 +/- 1.8 vs 3.5 +/- 0.8 [P < .001],
respectively). The apparent contrast-to-noise ratio between arteries and PEs was
higher for UTE than for MR angiography (20.3 +/- 5.2 vs 15.4 +/- 6.7, P = .055).
CONCLUSION: In a canine model, free-breathing 3D radial UTE performs better than
breath-hold 3D MR angiography in the detection of PE and yields better image
quality for visualization of small vessels and lung parenchyma. Free-breathing 3D
radial UTE for detection of PE is feasible and warrants evaluation in human
subjects.
PMID- 26422186
TI - A pilot study of what African American maternal caregivers and their adolescent
daughters talk about when asked to discuss tobacco together.
AB - Parents play a critical role in shaping their children's substance use behaviors,
yet few studies have examined the messages that caregivers give their adolescents
about tobacco. In this study, we identify tobacco-related messages discussed by
African American maternal caregivers and their adolescent daughters. Twenty-five
African American maternal caregivers and their adolescent daughters participated
in a video-taped discussion about tobacco. Discussions were transcribed and coded
thematically. Seven themes emerged, which were grouped into tobacco-messages and
communication strategies. Messages included health risks, non-health-related
reasons to stop smoking, reasons people smoke, and tobacco products and
marijuana. Strategies caregivers used to communicate their tobacco-related
messages included sharing personal or their families' experience with smoking,
using humor, and role-playing. Finally, embedded within all of the themes,
participants expressed their disapproval of tobacco use, whether it was directed
at their own use, their adolescents' use, a family members' use, or peers' use.
African American maternal caregivers and their daughters openly talk about a
variety of tobacco-related topics, and caregivers are open to sharing their own
and their families' experience with substance use. Findings also suggest that
having caregivers and their adolescents participate in discussions tasks could be
potentially beneficial in facilitating discussions and could identify areas in
which caregivers could use help in discussing sensitive topics.
PMID- 26422187
TI - The Association of Human Cytomegalovirus with Biomarkers of Inflammation and
Immune Activation in HIV-1-Infected Women.
AB - Three groups of cytomegalovirus (CMV)-seropositive women (total n = 164) were
selected from the Chicago Women's Interagency HIV-1 Study to investigate the
association between CMV coinfection and immune activation: (1) HIV-1 viremic, (2)
HIV-1 aviremic, and (3) HIV-1 uninfected. Quantitative measures of CMV serum IgG,
CMV DNA, and serum biomarkers interleukin (IL)-6, soluble CD163 (sCD163), soluble
CD14 (sCD14), and interferon gamma-induced protein (IP10) were obtained. Levels
of CMV IgG and the serum biomarkers were significantly higher in the HIV-1
viremic group compared to the aviremic and uninfected groups (p < 0.001). No
significant associations with CMV IgG levels were found for HIV-uninfected women.
When each of the HIV-infected groups was analyzed, sCD14 levels in the viremic
women were significantly associated with CMV IgG levels with p < 0.02 when
adjusted for age, CD4 count, and HIV viral load. There was also a modest
association (p = 0.036) with IL-6 from plasma and cervical vaginal lavage
specimens both unadjusted and adjusted for CD4 count and HIV viral load. The
association of CMV IgG level with sCD14 implicates the monocyte as a potential
site for interaction of the two viruses, which eventually may lead to non-AIDS
defining pathological conditions.
PMID- 26422188
TI - EBV-associated Burkitt lymphoma in Taiwan is not age-related.
AB - This study retrospectively investigated 54 cases of sporadic Burkitt lymphoma in
Taiwan with histopathology review, immunohistochemistry, Epstein-Barr virus (EBV)
in situ hybridization (EBER) and fluorescence in situ hybridization (FISH). The
great majority revealed typical immunophenotype and 89% (47/53) cases expressed
myc protein. EBER was positive in 20% (11/54) of cases, more frequently with
nodal presentation, but not significantly associated with age (pediatric vs.
adult), abdominal vs. extra-abdominal presentation or overall survival (OS). MYC
and IGH were rearranged in 94% (46/49) and 85% (41/48) of cases, respectively.
The concordance rate between myc expression and MYC translocation was 83%
(40/48). By univariate analysis, OS was statistically associated with age, with
or without chemotherapy, central nervous system (CNS) involvement, CNS
prophylaxis and leukemic transformation, but not gender, nodal vs. extranodal
involvement, stage, immunohistochemistry, EBER, myc expression, MYC translocation
or radiotherapy. By multivariate analysis, CNS involvement at presentation and
administration of chemotherapy were statistically associated with OS.
PMID- 26422189
TI - Using the Program Logic Model to Evaluate !Cuidate!: A Sexual Health Program for
Latino Adolescents in a School-Based Health Center.
AB - BACKGROUND: Addressing the disparities in pregnancy and sexually transmitted
infection (STI) rates for Latino youth in the United States requires an evidence
based approach. Although randomized controlled trials for sexual risk reduction
interventions have shown promise in improving short-term outcomes, program
sustainability has not been extensively examined in school settings where teens
spend time. Latina teen pregnancy rates are nearly twice the national average.
Adolescents comprise only 17% of the U.S. population, yet they account for 50% of
STIs. !Cuidate! is a high-impact sexual health group program endorsed by the
Centers for Disease Control and Prevention that has not been replicated in a real
world setting. AIMS: The program logic model (PLM) was used as the systematic
approach to plan, implement, and evaluate a sustainable model of sexual health
group programing (!Cuidate!) in a U.S. high school with a large Latino student
population. METHODS: The PLM provided the framework for the evaluation of
outputs, outcome, and impact. A multivariate repeated measures analysis of
variance was used as the means to evaluate the participant outcomes immediately
postprogram and at 8-12 weeks. RESULTS: !Cuidate! was executed within an existing
school structure and time constraints, below cost projections, and with high
participant retention (95.8%). Three cohorts (N = 24) of female teens
demonstrated significant increases in STI or HIV knowledge, self-efficacy, and
intention to use condoms (p < .01). Condom use increased postprogram. No
participants initiated sexual behavior, nor were there any reported pregnancies
or STIs. CONCLUSIONS: An evidence-based intervention previously tested in
randomized controlled trials can be sustained in a school-based health center
with similar results of efficacy. LINKING EVIDENCE TO ACTION: Our success served
as a platform for a sustainable program. We continue to extend the impact of the
program by delivering !Cuidate! in the school setting using a community health
worker.
PMID- 26422190
TI - The options of reversal of a dabigatran effect.
PMID- 26422191
TI - Synthetic cannabinoid hyperemesis resulting in rhabdomyolysis and acute renal
failure.
AB - Synthetic cannabinoid usage has increased in the past decade. Concurrently,
emergency management of associated adverse effects due to synthetic cannabinoid
usage has also risen. Reported toxicities include psychosis, seizures,
cardiotoxicity, acute kidney injury, and death. While cannabis was first
described as a cause of acute hyperemesis in 2004, a more recent case series also
describes the association between cannabinoid hyperemesis and risk of acute renal
failure. Synthetic cannabinoids have also been reported to cause acute
hyperemesis and acute renal failure; however, the risk of rhabdomyolysis-induced
renal failure has yet to be elucidated. In this article, we report the first
known case of synthetic cannabinoid hyperemesis leading to rhabdomyolysis and
acute renal failure.
PMID- 26422192
TI - Are physicians overlooking the clinical assessment of hypovolemia?
PMID- 26422193
TI - Basal Joint Arthroplasty and Radial-sided Carpal Tunnel Release Using a Single
Incision.
AB - PURPOSE: The purpose of our study was to determine in vivo outcomes and
consistency of relief of symptoms attributable to carpal tunnel syndrome in
patients who underwent radial-sided carpal tunnel release in conjunction with
basal joint arthroplasty through a single incision. MATERIALS AND METHODS: A
retrospective chart review identified all patients who had undergone radial-sided
carpal tunnel release in combination with basal joint arthroplasty at 1
institution from February 2011 through April 2014. Both preoperative and
postoperative symptoms attributable to carpal tunnel syndrome were documented.
Patient outcomes were assessed using the QuickDASH (Disabilities of the Arm,
Shoulder, and Hand) questionnaire. The mean length of follow-up was 16 months
(range, 2 to 37 mo). RESULTS: Eight patients (7 women; 10 extremities) were
available for follow-up. There was complete resolution of all symptoms
attributable to carpal tunnel syndrome in 9 of 10 extremities. There was complete
relief of paresthesias in the remaining extremity (and the patient reported
complete relief of night waking), as well as improvement but not resolution of
hypoesthesia and pain. CONCLUSIONS: Radial-sided carpal tunnel release performed
with basal joint arthroplasty through a single incision provided reliable
improvement or resolution of carpal tunnel syndrome symptoms.
PMID- 26422194
TI - Duration of dual antiplatelet therapy following drug-eluting coronary stents:
Longer or shorter?
PMID- 26422195
TI - Suicide attempts and completions in Veterans Affairs nursing home care units and
long-term care facilities: a review of root-cause analysis reports.
AB - OBJECTIVE: Suicide was the 10th leading cause of death for Americans in 2010. The
suicide rate is highest among men who are aged 75 and older. The prevalence of
suicidal behavior in nursing homes and long-term care (LTC) facilities was
estimated to be 1%. This study describes the systemic vulnerabilities found after
suicidal behavior in LTC facilities as well as steps to decrease or mitigate the
risk. METHOD: This is a retrospective review of root-cause analysis (RCA) reports
of suicide attempts and completions between 1 January 2000 and 31 December 2013
in the Veterans Health Administration LTC and nursing home care units. The RCA
reports of suicide attempts and completions were coded for patient demographics,
method of attempt or completion, root causes, and actions developed to address
the root cause. RESULTS: Thirty-five RCA reports were identified. The average age
was 65 years, 11 had a previous suicide attempt, and the primary mental health
diagnoses were depression, posttraumatic stress disorder, and schizophrenia. The
primary methods of self-harm were cutting with a sharp object, overdose, and
strangulation. CONCLUSIONS: It is recommended that all staff members are aware of
the signs and risk factors for depression and suicide in this population and
should systematically assess and treat mental disorders. In addition, LTC
facilities should have a standard protocol for evaluating the environment for
suicide hazards and use interdisciplinary teams to promote good communication
about risk factors identified among patients. Finally, staff should go beyond
staff education and policy to make clinical changes at the bedside. Published
2015. This article is a U.S. Government work and is in the public domain in the
USA.
PMID- 26422196
TI - Saying 'No' to PrEP research in Malawi: what constitutes 'failure' in offshored
HIV prevention research?
AB - Between 2004 and 2005, the first multi-sited clinical trial tested whether an
existing, marketed antiretroviral drug, Tenofovir (TDF), could prevent HIV
transmission. Referred to as pre-exposure prophylaxis (PrEP), most of these trial
sites prematurely closed down. Two sites located in Cambodia and Cameroon
received international media attention. But little attention was drawn to sites
in Malawi and Nigeria, where university ethicists and research scientists
extensively debated PrEP. This article focuses on events that took place in
Malawi where there was a prolonged dispute over the scientific rationales of PrEP
and not trial specific ethics referred to as 'bioethics'. Specifically, the
article discusses debates pertaining to three PrEP trial protocols that were
refused ethics approval in Malawi between 2004 and 2009. It is argued that HIV
science debates in Malawi are embedded in postcolonial politics--geopolitical
histories and state and household economic dispossessions that have created the
structural possibilities for Malawi to become an offshore destination for HIV
clinical research. As such, ethics in this case does not pertain to trial or
bioethical 'failures'. Rather, ethics is located at the scale of imperial
relations that give rise to multiple, often invisible, research concerns and
constraints.
PMID- 26422198
TI - Toward Highly Efficient Large-Area ITO-Free Organic Solar Cells with a
Conductance-Gradient Transparent Electrode.
AB - Highly efficient large-area organic solar cells (OSCs) with power conversion
efficiency up to 7.09%, and device area of 4 cm(2) are demonstrated on flexible
substrates. A conductance- or thickness-gradient ultra-thin Ag-based transparent
electrode is developed to better balance the light trapping and energy loss,
owing to the inhomogeneous energy-loss density on the large OSC sheet.
PMID- 26422197
TI - A Phase II Randomized Trial of Lycopene-Rich Tomato Extract Among Men with High
Grade Prostatic Intraepithelial Neoplasia.
AB - A diverse body of evidence suggests that lycopene might inhibit prostate cancer
development. We conducted a 6-mo repeat biopsy randomized trial among men with
high-grade prostatic intraepithelial neoplasia (HGPIN). Here we report results
for serum lycopene, prostate specific antigen (PSA) and insulin-like growth
factor (IGF) proteins, histopathological review, and tissue markers for
proliferation [minichromosome maintenance protein 2 (MCM-2)] and cell cycle
inhibition (p27). Participants consumed placebo or tomato extract capsules
containing 30 mg/day lycopene. Pre- and posttreatment biopsies were immunostained
and digitally scored. Serum lycopene was determined by LC-MS-MS. In secondary
analyses, pathologists blindly reviewed each biopsy to score histological
features. Fifty-eight men completed the trial. Serum lycopene increased 0.55
MUmol/L with treatment and declined 0.29 MUmol/L with placebo. We observed no
meaningful differences in PSA, IGF-1, or IGF binding protein 3 concentrations
between groups, nor any differences in expression of MCM-2 or p27 in epithelial
nuclei. Prevalences of cancer, HGPIN, atrophy, or inflammation posttreatment were
similar; however, more extensive atrophy and less extensive HGPIN was more common
in the lycopene group. Despite large differences in serum lycopene following
intervention, no treatment effects were apparent on either the serum or benign
tissue endpoints. Larger studies are warranted to determine whether changes
observed in extent of HGPIN and focal atrophy can be replicated.
PMID- 26422199
TI - Gamma-index method sensitivity for gauging plan delivery accuracy of volumetric
modulated arc therapy.
AB - PURPOSE: The aim of this study was to investigate the sensitivity of the gamma
index method according to various gamma criteria for volumetric modulated arc
therapy (VMAT). METHODS: Twenty head and neck (HN) and twenty prostate VMAT plans
were retrospectively selected for this study. Both global and local 2D gamma
evaluations were performed with criteria of 3%/3 mm, 2%/2 mm, 1%/2 mm and 2%/1
mm. In this study, the global and local gamma-index calculated the differences in
doses relative to the maximum dose and the dose at the current measurement point,
respectively. Using log files acquired during delivery, the differences in
parameters at every control point between the VMAT plans and the log files were
acquired. The differences in dose-volumetric parameters between reconstructed
VMAT plans using the log files and the original VMAT plans were calculated. The
Spearman's rank correlation coefficients (rs) were calculated between the passing
rates and those differences. RESULTS: Considerable correlations with statistical
significances were observed between global 1%/2 mm, local 1%/2 mm and local 2%/1
mm and the MLC position differences (rs = -0.712, -0.628 and -0.581). The numbers
of rs values with statistical significance between the passing rates and the
changes in dose-volumetric parameters were largest in global 2%/2 mm (n = 16),
global 2%/1 mm (n = 15) and local 2%/1 mm (n = 13) criteria. CONCLUSION: Local
gamma-index method with 2%/1 mm generally showed higher sensitivity to detect
deviations between a VMAT plan and the delivery of the VMAT plan.
PMID- 26422200
TI - Ultrasound versus Cone-beam CT image-guided radiotherapy for prostate and post
prostatectomy pretreatment localization.
AB - PURPOSE: To evaluate the accuracy of an intra-modality trans-abdominal ultrasound
(TA-US) device against soft-tissue based Cone-Beam Computed tomography (CBCT)
registration for prostate and post-prostatectomy pre-treatment positioning.
METHODS: The differences between CBCT and US shifts were calculated on 25
prostate cancer patients (cohort A) and 11 post-prostatectomy patients (cohort
B), resulting in 284 and 106 paired shifts for cohorts A and B, respectively. As
a second step, a corrective method was applied to the US registration results to
decrease the systematic shifts observed between TA-US and CBCT results. This
method consisted of subtracting the mean difference obtained between US and CBCT
registration results during the first 3 sessions from the US registration results
of the subsequent sessions. Inter-operator registration variability (IOV) was
also investigated for both modalities. RESULTS: After initial review, about 20%
of the US images were excluded because of insufficient quality. The average
differences between US and CBCT were: 2.8 +/- 4.1 mm, -0.9 +/- 4.2 mm, 0.4 +/-
3.4 mm for cohort A and 1.3 +/- 5.0 mm, -2.3 +/- 4.6 mm, 0.5 +/- 2.9 mm for
cohort B, in the anterior-posterior (AP), superior-inferior (SI) and lateral (LR)
directions, respectively. After applying the corrective method, only the
differences in the AP direction remained significant (p < 0.05). The IOV values
were between 0.6-2.0 mm and 2.1-3.5 mm for the CBCT and TA-US modalities,
respectively. CONCLUSIONS: Based on the obtained results and on the image
quality, the TA-US imaging modality is not safely interchangeable with CBCT for
pre-treatment repositioning. Treatment margins adaptation based on the correction
of the systematic shifts should be considered.
PMID- 26422202
TI - Equivalent Porous Media (EPM) Simulation of Groundwater Hydraulics and
Contaminant Transport in Karst Aquifers.
AB - Karst aquifers have a high degree of heterogeneity and anisotropy in their
geologic and hydrogeologic properties which makes predicting their behavior
difficult. This paper evaluates the application of the Equivalent Porous Media
(EPM) approach to simulate groundwater hydraulics and contaminant transport in
karst aquifers using an example from the North Coast limestone aquifer system in
Puerto Rico. The goal is to evaluate if the EPM approach, which approximates the
karst features with a conceptualized, equivalent continuous medium, is feasible
for an actual project, based on available data and the study scale and purpose.
Existing National Oceanic Atmospheric Administration (NOAA) data and previous
hydrogeological U. S. Geological Survey (USGS) studies were used to define the
model input parameters. Hydraulic conductivity and specific yield were estimated
using measured groundwater heads over the study area and further calibrated
against continuous water level data of three USGS observation wells. The water
table fluctuation results indicate that the model can practically reflect the
steady-state groundwater hydraulics (normalized RMSE of 12.4%) and long-term
variability (normalized RMSE of 3.0%) at regional and intermediate scales and can
be applied to predict future water table behavior under different hydrogeological
conditions. The application of the EPM approach to simulate transport is limited
because it does not directly consider possible irregular conduit flow pathways.
However, the results from the present study suggest that the EPM approach is
capable to reproduce the spreading of a TCE plume at intermediate scales with
sufficient accuracy (normalized RMSE of 8.45%) for groundwater resources
management and the planning of contamination mitigation strategies.
PMID- 26422201
TI - Improved Estimation of Human Lipoprotein Kinetics with Mixed Effects Models.
AB - CONTEXT: Mathematical models may help the analysis of biological systems by
providing estimates of otherwise un-measurable quantities such as concentrations
and fluxes. The variability in such systems makes it difficult to translate
individual characteristics to group behavior. Mixed effects models offer a tool
to simultaneously assess individual and population behavior from experimental
data. Lipoproteins and plasma lipids are key mediators for cardiovascular disease
in metabolic disorders such as diabetes mellitus type 2. By the use of
mathematical models and tracer experiments fluxes and production rates of
lipoproteins may be estimated. RESULTS: We developed a mixed effects model to
study lipoprotein kinetics in a data set of 15 healthy individuals and 15
patients with type 2 diabetes. We compare the traditional and the mixed effects
approach in terms of group estimates at various sample and data set sizes.
CONCLUSION: We conclude that the mixed effects approach provided better estimates
using the full data set as well as with both sparse and truncated data sets.
Sample size estimates showed that to compare lipoprotein secretion the mixed
effects approach needed almost half the sample size as the traditional method.
PMID- 26422203
TI - Salicylic Acid Induces Changes in Mango Fruit that Affect Oviposition Behavior
and Development of the Oriental Fruit Fly, Bactrocera dorsalis.
AB - The Oriental fruit fly, Bactrocera dorsalis (Hendel) is an important quarantine
pest around the globe. Although measures for its control are implemented
worldwide through IPM and male annihilation, there is little effect on their
population. Hence, there is a need for new strategies to control this minacious
pest. A strategy that has received negligible attention is the induction of
'natural plant defenses' by phytohormones. In this study, we investigated the
effect of salicylic acid (SA) treatment of mango fruit (cv. Totapuri) on
oviposition and larval development of B. dorsalis. In oviposition choice assays,
gravid females laid significantly less eggs in SA treated compared to untreated
fruit. Headspace volatiles collected from SA treated fruit were less attractive
to gravid females compared to volatiles from untreated fruit. GC-MS analysis of
the headspace volatiles from SA treated and untreated fruit showed noticeable
changes in their chemical compositions. Cis-ocimene and 3-carene (attractants to
B. dorsalis) were reduced in the headspace volatiles of treated fruit. Further,
reduced pupae formation and adult emergence was observed in treated fruit
compared to control. Increased phenol and flavonoid content was recorded in
treated fruit. We also observed differential expression of anti-oxidative enzymes
namely catalase (CAT), polyphenoloxidase (PPO) and peroxidase (POD). In summary,
the results indicate that SA treatment reduced oviposition, larval development
and adult emergence of B. dorsalis and suggest a role of SA in enhancing mango
tolerance to B. dorsalis.
PMID- 26422204
TI - Strategies for Primary Prevention of Coronary Heart Disease Based on Risk
Stratification by the ACC/AHA Lipid Guidelines, ATP III Guidelines, Coronary
Calcium Scoring, and C-Reactive Protein, and a Global Treat-All Strategy: A
Comparative--Effectiveness Modeling Study.
AB - BACKGROUND: Several approaches have been proposed for risk-stratification and
primary prevention of coronary heart disease (CHD), but their comparative and
cost-effectiveness is unknown. METHODS: We constructed a state-transition
microsimulation model to compare multiple approaches to the primary prevention of
CHD in a simulated cohort of men aged 45-75 and women 55-75. Risk-stratification
strategies included the 2013 American College of Cardiology/American Heart
Association (ACC/AHA) guidelines on the treatment of blood cholesterol, the Adult
Treatment Panel (ATP) III guidelines, and approaches based on coronary artery
calcium (CAC) scoring and C-reactive protein (CRP). Additionally we assessed a
treat-all strategy in which all individuals were prescribed either moderate-dose
or high-dose statins and all males received low-dose aspirin. Outcome measures
included CHD events, costs, medication-related side effects, radiation
attributable cancers, and quality-adjusted-life-years (QALYs) over a 30-year
timeframe. RESULTS: Treat-all with high-dose statins dominated all other
strategies for both men and women, gaining 15.7 million QALYs, preventing 7.3
million myocardial infarctions, and saving over $238 billion, compared to the
status quo, far outweighing its associated adverse events including bleeding,
hepatitis, myopathy, and new-onset diabetes. ACC/AHA guidelines were more cost
effective than ATP III guidelines for both men and women despite placing 8.7
million more people on statins. For women at low CHD risk, treat-all with high
dose statins was more likely to cause a statin-related adverse event than to
prevent a CHD event. CONCLUSIONS: Despite leading to a greater proportion of the
population placed on statin therapy, the ACC/AHA guidelines are more cost
effective than ATP III. Even so, at generic prices, treating all men and women
with statins and all men with low-dose aspirin appears to be more cost-effective
than all risk-stratification approaches for the primary prevention of CHD.
Especially for low-CHD risk women, decisions on the appropriate primary
prevention strategy should be based on shared decision making between patients
and healthcare providers.
PMID- 26422205
TI - Statistical Mechanics and Thermodynamics of Viral Evolution.
AB - This paper uses methods drawn from physics to study the life cycle of viruses.
The paper analyzes a model of viral infection and evolution using the "grand
canonical ensemble" and formalisms from statistical mechanics and thermodynamics.
Using this approach we enumerate all possible genetic states of a model virus and
host as a function of two independent pressures-immune response and system
temperature. We prove the system has a real thermodynamic temperature, and
discover a new phase transition between a positive temperature regime of normal
replication and a negative temperature "disordered" phase of the virus. We
distinguish this from previous observations of a phase transition that arises as
a function of mutation rate. From an evolutionary biology point of view, at
steady state the viruses naturally evolve to distinct quasispecies. This paper
also reveals a universal relationship that relates the order parameter (as a
measure of mutational robustness) to evolvability in agreement with recent
experimental and theoretical work. Given that real viruses have finite length RNA
segments that encode proteins which determine virus fitness, the approach used
here could be refined to apply to real biological systems, perhaps providing
insight into immune escape, the emergence of novel pathogens and other results of
viral evolution.
PMID- 26422206
TI - Efferent Vestibular Neurons Show Homogenous Discharge Output But Heterogeneous
Synaptic Input Profile In Vitro.
AB - Despite the importance of our sense of balance we still know remarkably little
about the central control of the peripheral balance system. While previous work
has shown that activation of the efferent vestibular system results in modulation
of afferent vestibular neuron discharge, the intrinsic and synaptic properties of
efferent neurons themselves are largely unknown. Here we substantiate the
location of the efferent vestibular nucleus (EVN) in the mouse, before
characterizing the input and output properties of EVN neurons in vitro. We made
transverse serial sections through the brainstem of 4-week-old mice, and
performed immunohistochemistry for calcitonin gene-related peptide (CGRP) and
choline acetyltransferase (ChAT), both expressed in the EVN of other species. We
also injected fluorogold into the posterior canal and retrogradely labelled
neurons in the EVN of ChAT:: tdTomato mice expressing tdTomato in all cholinergic
neurons. As expected the EVN lies dorsolateral to the genu of the facial nerve
(CNVII). We then made whole-cell current-, and voltage-clamp recordings from
visually identified EVN neurons. In current-clamp, EVN neurons display a
homogeneous discharge pattern. This is characterized by a high frequency burst of
action potentials at the onset of a depolarizing stimulus and the offset of a
hyperpolarizing stimulus that is mediated by T-type calcium channels. In voltage
clamp, EVN neurons receive either exclusively excitatory or inhibitory inputs, or
a combination of both. Despite this heterogeneous mixture of inputs, we show that
synaptic inputs onto EVN neurons are predominantly excitatory. Together these
findings suggest that the inputs onto EVN neurons, and more specifically the
origin of these inputs may underlie EVN neuron function.
PMID- 26422207
TI - VEP Responses to Op-Art Stimuli.
AB - Several types of striped patterns have been reported to cause adverse sensations
described as visual discomfort. Previous research using op-art-based stimuli has
demonstrated that spurious eye movement signals can cause the experience of
illusory motion, or shimmering effects, which might be perceived as
uncomfortable. Whilst the shimmering effects are one cause of discomfort, another
possible contributor to discomfort is excessive neural responses: As striped
patterns do not have the statistical redundancy typical of natural images, they
are perhaps unable to be encoded efficiently. If this is the case, then this
should be seen in the amplitude of the EEG response. This study found that
stimuli that were judged to be most comfortable were also those with the lowest
EEG amplitude. This provides some support for the idea that excessive neural
responses might also contribute to discomfort judgements in normal populations,
in stimuli controlled for perceived contrast.
PMID- 26422209
TI - The hydrochloride and hydrobromide salt forms of (S)-amphetamine.
AB - Despite the high profile of amphetamine, there have been relatively few
structural studies of its salt forms. The lack of any halide salt forms is
surprising as the typical synthetic route for amphetamine initially produces the
chloride salt. (S)-Amphetamine hydrochloride [systematic name: (2S)-1
phenylpropan-2-aminium chloride], C9H14N(+).Cl(-), has a Z' = 6 structure with
six independent cation-anion pairs. That these are indeed crystallographically
independent is supported by different packing orientations of the cations and by
the observation of a wide range of cation conformations generated by rotation
about the phenyl-CH2 bond. The supramolecular contacts about the anions also
differ, such that both a wide variation in the geometry of the three N-H...Cl
hydrogen bonds formed by each chloride anion and differences in C-H...Cl contacts
are apparent. (S)-Amphetamine hydrobromide [systematic name: (2S)-1-phenylpropan
2-aminium bromide], C9H14N(+).Br(-), is broadly similar to the hydrochloride in
terms of cation conformation, the existence of three N-H...X hydrogen-bond
contacts per anion and the overall two-dimensional hydrogen-bonded sheet motif.
However, only the chloride structure features organic bilayers and Z' > 1.
PMID- 26422208
TI - Magnitude of Treatment Abandonment in Childhood Cancer.
AB - BACKGROUND: Treatment abandonment (TxA) is recognized as a leading cause of
treatment failure for children with cancer in low-and-middle-income countries
(LMC). However, its global frequency and burden have remained elusive due to lack
of global data. This study aimed to obtain an estimate using survey and
population data. METHODS: Childhood cancer clinicians (medical oncologists,
surgeons, and radiation therapists), nurses, social workers, and psychologists
involved in care of children with cancer were approached through an online survey
February-May 2012. Incidence and population data were obtained from public
sources. Descriptive, univariable, and multivariable analyses were conducted.
RESULTS: 602 responses from 101 countries were obtained from physicians (84%),
practicing pediatric hematology/oncology (83%) in general or children's hospitals
(79%). Results suggested, 23,854 (15%) of 155,088 children <15 years old newly
diagnosed with cancer annually in the countries analyzed, abandon therapy.
Importantly, 83% of new childhood cancer cases and 99% of TxA were attributable
to LMC. The annual number of cases of TxA expected in LMC worldwide (26,166) was
nearly equivalent to the annual number of cancer cases in children <15 years
expected in HIC (26,368). Approximately two thirds of LMC had median TxA >= 6%,
but TxA >= 6% was reported in high- (9%), upper-middle- (41%), lower-middle-
(80%), and low-income countries (90%, p<0.001). Most LMC centers reporting TxA >
6% were outside the capital. Lower national income category, higher reliance on
out-of-pocket payments, and high prevalence of economic hardship at the center
were independent contextual predictors for TxA >= 6% (p<0.001). Global survival
data available for more developed and less developed regions suggests TxA may
account for at least a third of the survival gap between HIC and LMC. CONCLUSION:
Results show TxA is prevalent (compromising cancer survival for 1 in 7 children
globally), confirm the suspected high burden of TxA in LMC, and illustrate the
negative impact of poverty on its occurrence. The present estimates may appear
small compared to the global burden of child death from malnutrition and
infection (measured in millions). However, absolute numbers suggest the burden of
TxA in LMC is nearly equivalent to annually losing all kids diagnosed with cancer
in HIC just to TxA, without even considering deaths from disease progression,
relapse or toxicity-the main causes of childhood cancer mortality in HIC. Results
document the importance of monitoring and addressing TxA as part of childhood
cancer outcomes in at-risk settings.
PMID- 26422210
TI - Two different anionic manganese(II) coordination polymers constructed through
dicyanamide coordination bridges.
AB - In order to explore new metal coordination polymers and to search for new types
of ferroelectrics among hybrid coordination polymers, two manganese dicyanamide
complexes, poly[tetramethylammonium [di-MU3-dicyanamido-kappa(6)N(1):N(3):N(5)
tri-MU2-dicyanamido-kappa(6)N(1):N(5)-dimanganese(II)]],
{[(CH3)4N][Mn2(NCNCN)5]}n, (I), and catena-poly[bis(butyltriphenylphosphonium)
[[(dicyanamido-kappaN(1))manganese(II)]-di-MU2-dicyanamido-kappa(4)N(1):N(5)]],
{[(C4H9)(C6H5)3P]2[Mn(NCNCN)4]}n, (II), were synthesized in aqueous solution. In
(I), one Mn(II) cation is octahedrally coordinated by six nitrile N atoms from
six anionic dicyanamide (dca) ligands, while the second Mn(II) cation is
coordinated by four nitrile N atoms and two amide N atoms from six anionic dca
ligands. Neighbouring Mn(II) cations are linked together by MU-1,5- and MU-1,3,5
bridging dca anions to form a three-dimensional polymeric structure. The anionic
framework exhibits a solvent-accessible void of 289.8 A(3), amounting to 28.0% of
the total unit-cell volume. Each of the cavities in the network is occupied by
only one tetramethylammonium cation. In (II), each Mn(II) cation is octahedrally
coordinated by six nitrile N atoms from six dca ligands. Neighbouring Mn(II)
cations are linked together by double dca bridges to form a one-dimensional
polymeric chain, and C-H...N hydrogen-bonding interactions are involved in the
formation of the one-dimensional layer structure.
PMID- 26422211
TI - A moderate distortion of the 'picket-fence' porphyrin (cryptand-222)potassium
chlorido[meso-alpha,alpha,alpha,alpha-tetrakis(o
pivalamidophenyl)porphyrinato]ferrate(II) n-hexane monosolvate.
AB - As representative porphyrin model compounds, the structures of 'picket-fence'
porphyrins have been studied intensively. The title solvated complex salt
{systematic name: (4,7,13,16,21,24-hexaoxa-1,10
diazabicyclo[8.8.8]hexacosane)potassium(I) [5,10,15,20-tetrakis(2-tert
butanamidophenyl)porphyrinato]iron(II) n-hexane monosolvate},
[K(C18H36N2O6)][Fe(C64H64N8O4)Cl].C6H14 or [K(222)][Fe(TpivPP)Cl].C6H14 [222 is
cryptand-222 or 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane, and
TpivPP is meso-alpha,alpha,alpha,alpha-tetrakis(o-pivalamidophenyl)porphyrinate(2
)], [K(222)][Fe(TpivPP)Cl].C6H14, is a five-coordinate high-spin iron(II) picket
fence porphyrin complex. It crystallizes with a potassium cation chelated inside
a cryptand-222 molecule; the average K-O and K-N distances are 2.81 (2) and 3.05
(2) A, respectively. One of the protecting tert-butyl pickets is disordered. The
porphyrin plane presents a moderately ruffled distortion, as suggested by the
atomic displacements. The axial chloride ligand is located inside the molecular
cavity on the hindered porphyrin side and the Fe-Cl bond is tilted slightly off
the normal to the porphyrin plane by 4.1 degrees . The out-of-plane displacement
of the metal centre relative to the 24-atom mean plane (Delta24) is 0.62 A,
indicating a noticeable doming of the porphyrin core.
PMID- 26422212
TI - Structure and packing of aminoxyl and piperidinyl acrylamide monomers.
AB - The closely related title compounds, 4-acrylamido-2,2,6,6-tetramethylpiperidine-1
oxyl, C12H21N2O2, (I), and N-(2,2,6,6-tetramethylpiperidin-4-yl)acrylamide
monohydrate, C12H22N2O.H2O, (II), are important monomers in the preparation of
redox-active polymers. They comprise an acrylamide group of the usual s-cis
configuration appended to a 2,2,6,6-tetramethyl-substituted piperidine-1-oxyl
radical or a piperidinyl chair, respectively. The adjacent amide and piperidinyl
H atoms are approximately trans across the C-N bond. The packing in (I) is
dominated by N-H...O hydrogen bonds; these are supported by C-H...O contacts to
form an R2(1)(6) ring repeat, a motif which has been observed in other acrylamide
structures. In (II), hydrogen bonds are again key to the packing arrangements. In
this case, the incorporated solvent water molecule acts as an acceptor through
its O atom and as a donor through both H atoms, binding three adjacent
piperidinylacrylamide molecules into layers. In both structures, weak C-H...O
contacts involving the piperidinyl methyl H atoms and a proximal acrylamide
carbonyl O atom extend the structure in the third dimension.
PMID- 26422213
TI - Unusual centrosymmetric structure of [M(18-crown-6)](+) (M = Rb, Cs and NH4)
complexes stabilized in an environment of hexachloridoantimonate(V) anions.
AB - In (1,4,7,10,13,16-hexaoxacyclooctadecane)rubidium hexachloridoantimonate(V),
[Rb(C12H24O6)][SbCl6], (1), and its isomorphous caesium {(1,4,7,10,13,16
hexaoxacyclooctadecane)caesium hexachloridoantimonate(V), [Cs(C12H24O6)][SbCl6]},
(2), and ammonium {ammonium hexachloridoantimonate(V)-1,4,7,10,13,16
hexaoxacyclooctadecane (1/1), (NH4)[SbCl6].C12H24O6}, (3), analogues, the
hexachloridoantimonate(V) anions and 18-crown-6 molecules reside across -3 axes
passing through the Sb atoms and the centroids of the 18-crown-6 groups, both of
which coincide with centres of inversion. The Rb(+) [in (1)], Cs(+) [in (2)] and
NH4(+) [in (3)] cations are situated inside the cavity of the 18-crown-6 ring;
they are situated on -3 axes and are equally disordered about centres of
inversion, deviating from the centroid of the 18-crown-6 molecule by 0.4808 (13),
0.9344 (7) and 0.515 (8) A, respectively. Interaction of the ammonium cation and
the 18-crown-6 group is supported by three equivalent hydrogen bonds [N...O =
2.928 (3) A and N-H...O = 162 degrees ]. The centrosymmetric structure of [Cs(18
crown-6)](+), with the large Cs(+) cation approaching the centre of the ligand
cavity, is unprecedented and accompanied by unusually short Cs-O bonds [2.939 (2)
and 3.091 (2) A]. For all three compounds, the [M(18-crown-6)](+) cations and
[SbCl6](-) anions afford linear stacks along the c axis, with the cationic
complexes embedded between pairs of inversion-related anions.
PMID- 26422214
TI - Polymorphism in 3-acetyl-4-hydroxy-2H-chromen-2-one.
AB - A new polymorph (denoted polymorph II) of 3-acetyl-4-hydroxy-2H-chromen-2-one,
C11H8O4, was obtained unexpectedly during an attempt to recrystallize the
compound from salt-melted ice, and the structure is compared with that of the
original polymorph (denoted polymorph I) [Lyssenko & Antipin (2001). Russ. Chem.
Bull. 50, 418-431]. Strong intramolecular O-H...O hydrogen bonds are observed
equally in the two polymorphs [O...O = 2.4263 (13) A in polymorph II and 2.442
(1) A in polymorph I], with a slight delocalization of the hydroxy H atom towards
the ketonic O atom in polymorph II [H...O = 1.32 (2) A in polymorph II and 1.45
(3) A in polymorph I]. In both crystal structures, the packing of the molecules
is dominated and stabilized by weak intermolecular C-H...O hydrogen bonds.
Additional pi-pi stacking interactions between the keto-enol hydrogen-bonded
rings stabilize polymorph I [the centres are separated by 3.28 (1) A], while
polymorph II is stabilized by interactions between alpha-pyrone rings, which are
parallel to one another and separated by 3.670 (5) A.
PMID- 26422215
TI - Two new cadmium(II) coordination polymers based on bis(1,2,4-triazol-1-yl)alkane
ligands and pyrazine-2,3-dicarboxylic acid.
AB - Assemblies of pyrazine-2,3-dicarboxylic acid and Cd(II) in the presence of
bis(1,2,4-triazol-1-yl)butane or bis(1,2,4-triazol-1-yl)ethane under ambient
conditions yielded two new coordination polymers, namely poly[[tetraaqua[MU2-1,4
bis(1,2,4-triazol-1-yl)butane-kappa(2)N(4):N(4')]bis(MU2-pyrazine-2,3
dicarboxylato-kappa(3)N(1),O(2):O(3))dicadmium(II)] dihydrate],
{[Cd2(C6H2N2O4)2(C8H12N6)(H2O)4].2H2O}n, (I), and poly[[diaqua[MU2-1,2-bis(1,2,4
triazol-1-yl)ethane-kappa(2)N(4):N(4')]bis(MU3-pyrazine-2,3-dicarboxylato
kappa(4)N(1),O(2):O(3):O(3'))dicadmium(II)] dihydrate],
{[Cd2(C6H2N2O4)2(C6H8N6)(H2O)2].2H2O}n, (II). Complex (I) displays an interesting
two-dimensional wave-like structure and forms a distinct extended three
dimensional supramolecular structure with the help of O-H...N and O-H...O
hydrogen bonds. Complex (II) has a three-dimensional framework structure in which
hydrogen bonds of the O-H...N and O-H...O types are found.
PMID- 26422216
TI - A structural study of Si6-ring-containing [Si6Cl14](2-) chlorosilicates.
AB - The crystal structures of four substituted-ammonium dichloride
dodecachlorohexasilanes are presented. Each is crystallized with a different
cation and one of the structures contains a benzene solvent molecule:
bis(tetraethylammonium) dichloride dodecachlorohexasilane, 2C8H20N(+).2Cl(
).Cl12Si6, (I), tetrabutylammonium tributylmethylammonium dichloride
dodecachlorohexasilane, C16H36N(+).C13H30N(+).2Cl(-).Cl12Si6, (II),
bis(tetrabutylammonium) dichloride dodecachlorohexasilane benzene disolvate,
2C16H36N(+).2Cl(-).Cl12Si6.2C6H6, (III), and bis(benzyltriphenylphosphonium)
dichloride dodecachlorohexasilane, 2C25H22P(+).2Cl(-).Cl12Si6, (IV). In all four
structures, the dodecachlorohexasilane ring is located on a crystallographic
centre of inversion. The geometry of the dichloride dodecachlorohexasilanes in
the different structures is almost the same, irrespective of the cocrystallized
cation and solvent. However, the crystal structure of the parent
dodecachlorohexasilane molecule shows that this molecule adopts a chair
conformation. In (IV), the P atom and the benzyl group of the cation are
disordered over two sites, with a site-occupation factor of 0.560 (5) for the
major-occupied site.
PMID- 26422217
TI - A new Co(II) complex of diniconazole: synthesis, crystal structure and antifungal
activity.
AB - A new Co(II) complex of diniconazole, namely diaqua[(E)-(RS)-1-(2,4
dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl-kappaN(4))pent-1-en-3
ol]cobalt(II) dinitrate dihydrate, [Co(C15H17Cl2N3O)3(H2O)2](NO3)2.2H2O, was
synthesized and characterized by elemental analysis, IR spectroscopy and single
crystal X-ray diffraction. Crystal structural analysis shows that the
centrosymmetric Co(II) cation is coordinated by four diniconazole ligands and two
water molecules, forming a six-coordinated octahedral structure. There are also
two free nitrate counter-anions and two additional solvent water molecules in the
structure. Intermolecular O-H...O hydrogen bonds link the complex cations into a
one-dimensional chain. In addition, the antifungal activity of the complex
against Botryosphaeria ribis, Gibberella nicotiancola, Botryosphaeria berengriana
and Alternariasolani was studied. The results indicate that the complex shows a
higher antifungal activity for Botryosphaeria ribis and Botryosphaeria
berengriana than diniconazole, but a lower antifungal activity for Gibberella
nicotiancola and Alternariasolani.
PMID- 26422218
TI - Synthesis and structure determination of seven ternary bismuthides: crystal
chemistry of the RELi3Bi2 family (RE = La-Nd, Sm, Gd, and Tb).
AB - Zintl phases are renowned for their diverse crystal structures with rich
structural chemistry and have recently exhibited some remarkable heat- and charge
transport properties. The ternary bismuthides RELi3Bi2 (RE = La-Nd, Sm, Gd, and
Tb) (namely, lanthanum trilithium dibismuthide, LaLi3Bi2, cerium trilithium
dibismuthide, CeLi3Bi2, praseodymium trilithium dibismuthide, PrLi3Bi2, neodymium
trilithium dibismuthide, NdLi3Bi2, samarium trilithium dibismuthide, SmLi3Bi2,
gadolinium trilithium dibismuthide, GdLi3Bi2, and terbium trilithium
dibismuthide, TbLi3Bi2) were synthesized by high-temperature reactions of the
elements in sealed Nb ampoules. Single-crystal X-ray diffraction analysis shows
that all seven compounds are isostructural and crystallize in the LaLi3Sb2 type
structure in the trigonal space group P-3m1 (Pearson symbol hP6). The unit-cell
volumes decrease monotonically on moving from the La to the Tb compound, owing to
the lanthanide contraction. The structure features a rare-earth metal atom and
one Li atom in a nearly perfect octahedral coordination by six Bi atoms. The
second crystallographically unique Li atom is surrounded by four Bi atoms in a
slightly distorted tetrahedral geometry. The atomic arrangements are best
described as layered structures consisting of two-dimensional layers of fused
LiBi4 tetrahedra and LiBi6 octahedra, separated by rare-earth metal cations. As
such, these compounds are expected to be valance-precise semiconductors, whose
formulae can be represented as (RE(3+))(Li(1+))3(Bi(3-))2.
PMID- 26422219
TI - Halogen-bonded adduct of 1,2-dibromo-1,1,2,2-tetrafluoroethane and 1,4
diazabicyclo[2.2.2]octane.
AB - Halogen bonding is an intermolecular interaction capable of being used to direct
extended structures. Typical halogen-bonding systems involve a noncovalent
interaction between a Lewis base, such as an amine, as an acceptor and a halogen
atom of a halofluorocarbon as a donor. Vapour-phase diffusion of 1,4
diazabicyclo[2.2.2]octane (DABCO) with 1,2-dibromotetrafluoroethane results in
crystals of the 1:1 adduct, C2Br2F4.C6H12N2, which crystallizes as an infinite
one-dimensional polymeric structure linked by intermolecular N...Br halogen bonds
[2.829 (3) A], which are 0.57 A shorter than the sum of the van der Waals radii.
PMID- 26422220
TI - The first three-dimensional Fe(III)-Sr(II) heterometallic coordination polymer:
poly[[diaquatetrakis(MU3-pyridine-2,3-dicarboxylato)diiron(III)strontium(II)]
dihydrate].
AB - The title compound, poly[[diaqua-1kappa(2)O-tetrakis(MU3-pyridine-2,3
dicarboxylato)
2:1:2'kappa(10)N,O(2):O(2'),O(3):O(3');2:1:2'kappa(8)O(3):O(3'):N,O(2)
diiron(III)strontium(II)] dihydrate], {[Fe2Sr(C7H3O4)4(H2O)2].2H2O}n, which has
triclinic (P-1) symmetry, was prepared by the reaction of pyridine-2,3
dicarboxylic acid, SrCl2.6H2O and Fe(OAc)2(OH) (OAc is acetate) in the presence
of imidazole in water at 363 K. In the crystal structure, the pyridine-2,3
dicarboxylate (pydc(2-)) ligand exhibits MU3-eta(1),eta(1):eta(1):eta(1) and MU3
eta(1),eta(1):eta(1),eta(1):eta(1) coordination modes, bridging two Fe(III)
cations and one Sr(II) cation. The Sr(II) cation, which is located on an
inversion centre, is eight-coordinated by six O atoms of four pydc(2-) ligands
and two water molecules. The coordination geometry of the Sr(II) cation can be
best described as distorted dodecahedral. The Fe(III) cation is six-coordinated
by O and N atoms of four pydc(2-) ligands in a slightly distorted octahedral
geometry. Each Fe(III) cation bridges two neighbouring Fe(III) cations to form a
one-dimensional [Fe2(pydc)4]n chain. The chains are connected by Sr(II) cations
to form a three-dimensional framework. The topology type of this framework is
tfj. The structure displays O-H...O and C-H...O hydrogen bonding.
PMID- 26422221
TI - Photoluminescence properties of a cationic trinuclear zinc(II) complex with the
tetradentate Schiff base ligand 6-methyl-2-({[(pyridin-2
yl)methyl]imino}methyl)phenolate.
AB - Metal complexes with Schiff base ligands have been suggested as potential
phosphors in electroluminescent devices. In the title complex, tetrakis[6-methyl
2-({[(pyridin-2-yl)methyl]imino}methyl)phenolato
1:2kappa(8)N,N',O:O;3:2kappa(8)N,N',O:O]trizinc(II) hexafluoridophosphate
methanol monosolvate, [Zn3(C14H13N2O)4](PF6)2.CH3OH, the Zn(II) cations adopt
both six- and four-coordinate geometries involving the N and O atoms of
tetradentate 6-methyl-2-({[(pyridin-2-yl)methyl]imino}methyl)phenolate ligands.
Two terminal Zn(II) cations adopt distorted octahedral geometries and the central
Zn(II) cation adopts a distorted tetrahedral geometry. The O atoms of the
phenolate ligands bridge three Zn(II) cations, forming a dicationic trinuclear
metal cluster. The title complex exhibits a strong emission at 469 nm with a
quantum yield of 15.5%.
PMID- 26422222
TI - 5-Iodouracil: structure of a reflection twin.
AB - The crystal structure of 5-iodouracil, C4H3IN2O2, has been determined in the
noncentrosymmetric space group P21 on a nonmerohedrally twinned crystal. Both
twin components are enantiomorphically pure, but the twin element is a mirror
plane perpendicular to c*. The molecular structure is discussed and stacking
faults in the two-dimensional packing are proposed as a reason for the twinning.
PMID- 26422223
TI - Methods of space-group determination - a supplement dealing with twinned crystals
and metric specialization.
AB - Tables for the determination of space group for single crystals, twinned crystals
and crystals with a specialized metric are presented in the form of a spreadsheet
for use on a computer. There are 14 tables, one for each of the Bravais-lattice
types. The content of the tables is arranged so that at the intersection of rows,
displaying the conditions for reflection, and of columns, displaying the Laue and
crystal classes, one finds those space groups compatible with the observed
Bravais-lattice type, the conditions for reflection and the Laue and crystal
classes. The tables are intended to be of direct use to an experimentalist
working with an unknown structure.
PMID- 26422224
TI - Crystal structures of four delta-keto esters and a Cambridge Structural Database
analysis of cyano-halogen interactions.
AB - The revived interest in halogen bonding as a tool in pharmaceutical cocrystals
and drug design has indicated that cyano-halogen interactions could play an
important role. The crystal structures of four closely related delta-keto esters,
which differ only in the substitution at a single C atom (by H, OMe, Cl and Br),
are compared, namely ethyl 2-cyano-5-oxo-5-phenyl-3-(piperidin-1-yl)pent-2
enoate, C19H22N2O3, (1), ethyl 2-cyano-5-(4-methoxyphenyl)-5-oxo-3-(piperidin-1
yl)pent-2-enoate, C20H24N2O4, (2), ethyl 5-(4-chlorophenyl)-2-cyano-5-oxo-3
(piperidin-1-yl)pent-2-enoate, C19H21ClN2O3, (3), and the previously published
ethyl 5-(4-bromophenyl)-2-cyano-5-oxo-3-(piperidin-1-yl)pent-2-enoate,
C19H21BrN2O3, (4) [Maurya, Vasudev & Gupta (2013). RSC Adv. 3, 12955-12962]. The
molecular conformations are very similar, while there are differences in the
molecular assemblies. Intermolecular C-H...O hydrogen bonds are found to be the
primary interactions in the crystal packing and are present in all four
structures. The halogenated derivatives have additional aromatic-aromatic
interactions and cyano-halogen interactions, further stabilizing the molecular
packing. A database analysis of cyano-halogen interactions using the Cambridge
Structural Database [CSD; Groom & Allen (2014). Angew. Chem. Int. Ed. 53, 662
671] revealed that about 13% of the organic molecular crystals containing both
cyano and halogen groups have cyano-halogen interactions in their packing. Three
geometric parameters for the C-X...N[triple-bond]C interaction (X = F, Cl, Br or
I), viz. the N...X distance and the C-X...N and C-N...X angles, were analysed.
The results indicate that all the short cyano-halogen contacts in the CSD can be
classified as halogen bonds, which are directional noncovalent interactions.
PMID- 26422225
TI - One-dimensional Cu(II) coordination polymers containing C2h-symmetric 1,1':4',1''
terphenyl-3,3'-dicarboxylate linkers.
AB - Two new one-dimensional Cu(II) coordination polymers (CPs) containing the C2h
symmetric terphenyl-based dicarboxylate linker 1,1':4',1''-terphenyl-3,3'
dicarboxylate (3,3'-TPDC), namely catena-poly[[bis(dimethylamine
kappaN)copper(II)]-MU-1,1':4',1''-terphenyl-3,3'-dicarboxylato
kappa(4)O,O':O'':O'''] monohydrate], {[Cu(C20H12O4)(C2H7N)2].H2O}n, (I), and
catena-poly[[aquabis(dimethylamine-kappaN)copper(II)]-MU-1,1':4',1''-terphenyl
3,3'-dicarboxylato-kappa(2)O(3):O(3')] monohydrate],
{[Cu(C20H12O4)(C2H7N)2(H2O)].H2O}n, (II), were both obtained from two different
methods of preparation: one reaction was performed in the presence of 1,4
diazabicyclo[2.2.2]octane (DABCO) as a potential pillar ligand and the other was
carried out in the absence of the DABCO pillar. Both reactions afforded crystals
of different colours, i.e. violet plates for (I) and blue needles for (II), both
of which were analysed by X-ray crystallography. The 3,3'-TPDC bridging ligands
coordinate the Cu(II) ions in asymmetric chelating modes in (I) and in monodenate
binding modes in (II), forming one-dimensional chains in each case. Both
coordination polymers contain two coordinated dimethylamine ligands in mutually
trans positions, and there is an additional aqua ligand in (II). The solvent
water molecules are involved in hydrogen bonds between the one-dimensional
coordination polymer chains, forming a two-dimensional network in (I) and a three
dimensional network in (II).
PMID- 26422226
TI - Self-Compassion as a Resource in the Self-Stigma Process of Overweight and Obese
Individuals.
AB - OBJECTIVE: Self-stigma in overweight and obese individuals has strong
associations with impairment in mental and global health. This study sought to
explore self-compassion as a psychological resource in the self-stigma process.
METHODS: In a 2012 representative German population survey of N = 1,158
overweight and obese individuals, self-compassion was examined as a mediator
between self-stigma and mental and physical health outcomes, including BMI
(kg/m2), using structural equation modeling and controlling for sociodemographic
factors. RESULTS: Psychological variables were assessed using validated self
report questionnaires. Self-compassion partially mediated the relationships
between self-stigma and depression, somatic symptoms, and health status/quality
of life, lowering the predictive effect of self-stigma on the outcomes by
approximately one-third. In contrast, self-compassion, because it was unrelated
to BMI, did not mediate the association between self-stigma and BMI. CONCLUSION:
Self-compassion has the potential to act as a buffer against the mental and
global health detriments of self-stigma in overweight and obesity and could thus
represent a target for interventions to reduce self-stigma and prevent these
health impairments. In order to influence the association between self-stigma and
BMI, self-compassion should conceptually be linked to weight management.
PMID- 26422227
TI - Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system.
AB - The microbial adaptive immune system CRISPR mediates defense against foreign
genetic elements through two classes of RNA-guided nuclease effectors. Class 1
effectors utilize multi-protein complexes, whereas class 2 effectors rely on
single-component effector proteins such as the well-characterized Cas9. Here, we
report characterization of Cpf1, a putative class 2 CRISPR effector. We
demonstrate that Cpf1 mediates robust DNA interference with features distinct
from Cas9. Cpf1 is a single RNA-guided endonuclease lacking tracrRNA, and it
utilizes a T-rich protospacer-adjacent motif. Moreover, Cpf1 cleaves DNA via a
staggered DNA double-stranded break. Out of 16 Cpf1-family proteins, we
identified two candidate enzymes from Acidaminococcus and Lachnospiraceae, with
efficient genome-editing activity in human cells. Identifying this mechanism of
interference broadens our understanding of CRISPR-Cas systems and advances their
genome editing applications.
PMID- 26422228
TI - Lung function comparison between two decades in cystic fibrosis children: A
single centre study.
AB - OBJECTIVES: The purpose of this study was to compare two cohorts of cystic
fibrosis (CF) patients born and treated in two different decades, diagnosed
through a CF neonatal screening program. METHODOLOGY: We compared pulmonary
function decline from 10 to 15 years of age in patients with cystic fibrosis born
between 1979 and 1984 (Cohort 1) and between 1991 and 1996 (Cohort 2). Forced
expiratory volume in 1 sec (FEV1%) and forced expiratory flow from 25% to 75%
(FEF 25-75%) were analyzed by a linear mixed model approach. The differences
between the two cohorts were estimated and the overall cohort effect was tested.
RESULTS: Ninety-two patients (51 males, 41 females) fulfilled the selection
criteria. Pancreatic insufficiency and CF related diabetes were present in 91%
and 20% of patients, respectively. The mean absolute decrement of FEV1% was 9.2
(standard deviation [SD] 11.2) in Cohort 1 and 0.6 (SD 10.4) in Cohort 2 (P <
0.001). The mean decrement of FEF 25-75% was 16.3 (SD 19.5) in Cohort 1 and 1.3
(SD 16.8) in Cohort 2 (P < 0.001) and the Pseudomonas aeruginosa (Pa)
colonization was 28% and 15% respectively (P = 0.1). CONCLUSIONS: Our results
show that pulmonary function has clearly ameliorated over a decade in young CF
patients, in a period during which several significant therapeutic changes have
been introduced, such as dornase alfa, tobramycin and hypertonic saline. To our
knowledge this is the first study showing a cohort effect in patients diagnosed
after neonatal screening.
PMID- 26422229
TI - Tissue-Specific Enrichment of Lymphoma Risk Loci in Regulatory Elements.
AB - Though numerous polymorphisms have been associated with risk of developing
lymphoma, how these variants function to promote tumorigenesis is poorly
understood. Here, we report that lymphoma risk SNPs, especially in the non
Hodgkin's lymphoma subtype chronic lymphocytic leukemia, are significantly
enriched for co-localization with epigenetic marks of active gene regulation.
These enrichments were seen in a lymphoid-specific manner for numerous ENCODE
datasets, including DNase-hypersensitivity as well as multiple segmentation
defined enhancer regions. Furthermore, we identify putatively functional SNPs
that are both in regulatory elements in lymphocytes and are associated with gene
expression changes in blood. We developed an algorithm, UES, that uses a Monte
Carlo simulation approach to calculate the enrichment of previously identified
risk SNPs in various functional elements. This multiscale approach integrating
multiple datasets helps disentangle the underlying biology of lymphoma, and more
broadly, is generally applicable to GWAS results from other diseases as well.
PMID- 26422230
TI - Intratumor Heterogeneity of ALK-Rearrangements and Homogeneity of EGFR-Mutations
in Mixed Lung Adenocarcinoma.
AB - BACKGROUND: Non Small Cell Lung Cancer is a highly heterogeneous tumor.
Histologic intratumor heterogeneity could be 'major', characterized by a single
tumor showing two different histologic types, and 'minor', due to at least 2
different growth patterns in the same tumor. Therefore, a morphological
heterogeneity could reflect an intratumor molecular heterogeneity. To date, few
data are reported in literature about molecular features of the mixed
adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK
rearrangements in different intratumor subtypes and/or growth patterns in a
series of mixed adenocarcinomas and adenosquamous carcinomas. METHODS: 590 Non
Small Cell Lung Carcinomas tumor samples were revised in order to select mixed
adenocarcinomas with available tumor components. Finally, only 105 mixed
adenocarcinomas and 17 adenosquamous carcinomas were included in the study for
further analyses. Two TMAs were built selecting the different intratumor
histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR
mutations were detected through IHC and confirmed by RT-PCR. RESULTS: 10/122
cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity
of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the
EGFR-mutated protein in all histologic components. CONCLUSION: Our data suggests
that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK
rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas
and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements
could lead to a possible impact on the therapeutic responses and the disease
outcomes.
PMID- 26422231
TI - Narrative Exposure Therapy: A Proposed Model to Address Intimate Partner Violence
Related PTSD in Parenting and Pregnant Adolescents.
AB - Pregnant and parenting adolescents experience high rates of intimate partner
violence (IPV) and its sequelae posttraumatic stress disorder (PTSD) and
depression. Narrative exposure therapy (NET) is an innovative intervention that
has demonstrated strong preliminary evidence in improving mental health. The
specific aims of this article are 3-fold: (1) provide a brief background about
IPV-related PTSD and depression among pregnant and parenting adolescents; (2)
describe NET's theoretical principles, its therapeutic process, and provide a
review of existing evidence; and (3) discuss NET as a potential treatment to
address the mental health burden among adolescents experiencing IPV-related PTSD
and depression.
PMID- 26422232
TI - Particulate Matter Contributions from Agricultural Tilling Operations in an
Irrigated Desert Region.
AB - Sources of regional particulate matter (PM), particularly agricultural
operations, must be understood in order to manage the air quality in irrigated
dry climates. Direct monitoring measurements alone are useful, but not
sufficient, to estimate regional PM source concentrations. This paper combines
modeling with ground (point) and airplane (spatial) measurement methods to
estimate regional PM10 (PM diameter<=10 MUm) contributions from agricultural
operations. Hourly data from three air quality monitoring stations positioned at
a 2-m height located on the west and east mesas of New Mexico's Mesilla Valley
and in the valley at Anthony, NM were acquired from the New Mexico Air Quality
Bureau. The study spanned the agricultural tilling season, March 1 to April 30,
for the years 2008 to 2012. One- second spatial PM10 concentrations at 200 m
above the valley floor were measured during a two-hour controlled field tilling
operation on April 1, 2008. The HYSPLIT 4.0 (Hybrid Single-Particle Lagrangian
Integrated Trajectory version 4) model was run at the corresponding times and
heights, outputting PM10 concentrations from all potential agricultural tilling
operations. The calculated percentage contribution (modeled PM10
concentration/measured PM10 concentration) indicated that the near-surface (2-m
height) proportion from the agricultural operations for five seasonal averages
ranged from 0.7% to 1.5% on the west and east mesas and 1.3% for the valley site
at Anthony. There were 71 hourly high values of contribution ratios ranging from
30 to 100% at the three sites, depending on the wind speed and direction.
PMID- 26422234
TI - PATBox: A Toolbox for Classification and Analysis of P-Type ATPases.
AB - P-Type ATPases are part of the regulatory system of the cell where they are
responsible for transporting ions and lipids through the cell membrane. These
pumps are found in all eukaryotes and their malfunction has been found to cause
several severe diseases. Knowing which substrate is pumped by a certain P-Type
ATPase is therefore vital. The P-Type ATPases can be divided into 11 subtypes
based on their specificity, that is, the substrate that they pump. Determining
the subtype experimentally is time-consuming. Thus it is of great interest to be
able to accurately predict the subtype based on the amino acid sequence only. We
present an approach to P-Type ATPase sequence classification based on the k
nearest neighbors, similar to a homology search, and show that this method
provides performs very well and, to the best of our knowledge, better than any
existing method despite its simplicity. The classifier is made available as a web
service at http://services.birc.au.dk/patbox/ which also provides access to a
database of potential P-Type ATPases and their predicted subtypes.
PMID- 26422233
TI - Vitamin A Deficiency Impairs Mucin Expression and Suppresses the Mucosal Immune
Function of the Respiratory Tract in Chicks.
AB - The chicken immune system is immature at the time of hatching. The development of
the respiratory immune system after hatching is vital to young chicks. The aim of
this study was to investigate the effect of dietary vitamin A supplement levels
on respiratory mucin and IgA production in chicks. In this study, 120 one-day-old
broiler chicks were randomly divided into 4 groups consisting of three replicates
of 10 broilers and subjected to dietary vitamin A supplement levels of 0, 1,500,
6,000, or 12,000 IU/kg for seven days. Compared with control birds, vitamin A
supplementation significantly increased the mucin and IgA levels in the
bronchoalveolar lavage fluid (BALF) as well as the IgA level in serum. In the
lungs, vitamin A supplementation downregulated TNF-alpha and EGFR mRNA
expression. The TGF-beta and MUC5AC mRNA expression levels were upregulated by
vitamin A supplementation at a dose of 6,000 IU/kg, and the IL-13 mRNA expression
level was increased at the 12,000 IU/kg supplement level. Vitamin A deficiency
(control) significantly decreased the mRNA expression levels of MUC2, IgA, EGFR,
IL-13 and TGF-beta in trachea tissue. Histological section analysis revealed that
the number of goblet cells in the tracheal epithelium was less in the 0 and
12,000 IU/kg vitamin A supplement groups than in the other groups. In conclusion,
vitamin A deficiency suppressed the immunity of the airway by decreasing the IgA
and mucin concentrations in neonatal chicks. This study suggested that a suitable
level of vitamin A is essential for the secretion of IgA and mucin in the
respiratory tract by regulating the gene expression of cytokines and epithelial
growth factors.
PMID- 26422235
TI - Responding to Young People's Health Risks in Primary Care: A Cluster Randomised
Trial of Training Clinicians in Screening and Motivational Interviewing.
AB - OBJECTIVE: To evaluate the effectiveness of a complex intervention implementing
best practice guidelines recommending clinicians screen and counsel young people
across multiple psychosocial risk factors, on clinicians' detection of health
risks and patients' risk taking behaviour, compared to a didactic seminar on
young people's health. DESIGN: Pragmatic cluster randomised trial where volunteer
general practices were stratified by postcode advantage or disadvantage score and
billing type (private, free national health, community health centre), then
randomised into either intervention or comparison arms using a computer generated
random sequence. Three months post-intervention, patients were recruited from all
practices post-consultation for a Computer Assisted Telephone Interview and
followed up three and 12 months later. Researchers recruiting, consenting and
interviewing patients and patients themselves were masked to allocation status;
clinicians were not. SETTING: General practices in metropolitan and rural
Victoria, Australia. PARTICIPANTS: General practices with at least one interested
clinician (general practitioner or nurse) and their 14-24 year old patients.
INTERVENTION: This complex intervention was designed using evidence based
practice in learning and change in clinician behaviour and general practice
systems, and included best practice approaches to motivating change in adolescent
risk taking behaviours. The intervention involved training clinicians (nine
hours) in health risk screening, use of a screening tool and motivational
interviewing; training all practice staff (receptionists and clinicians) in
engaging youth; provision of feedback to clinicians of patients' risk data; and
two practice visits to support new screening and referral resources. Comparison
clinicians received one didactic educational seminar (three hours) on engaging
youth and health risk screening. OUTCOME MEASURES: Primary outcomes were patient
report of (1) clinician detection of at least one of six health risk behaviours
(tobacco, alcohol and illicit drug use, risks for sexually transmitted infection,
STI, unplanned pregnancy, and road risks); and (2) change in one or more of the
six health risk behaviours, at three months or at 12 months. Secondary outcomes
were likelihood of future visits, trust in the clinician after exit interview,
clinician detection of emotional distress and fear and abuse in relationships,
and emotional distress at three and 12 months. Patient acceptability of the
screening tool was also described for the intervention arm. Analyses were
adjusted for practice location and billing type, patients' sex, age, and
recruitment method, and past health risks, where appropriate. An intention to
treat analysis approach was used, which included multilevel multiple imputation
for missing outcome data. RESULTS: 42 practices were randomly allocated to
intervention or comparison arms. Two intervention practices withdrew post
allocation, prior to training, leaving 19 intervention (53 clinicians, 377
patients) and 21 comparison (79 clinicians, 524 patients) practices. 69% of
patients in both intervention (260) and comparison (360) arms completed the 12
month follow-up. Intervention clinicians discussed more health risks per patient
(59.7%) than comparison clinicians (52.7%) and thus were more likely to detect a
higher proportion of young people with at least one of the six health risk
behaviours (38.4% vs 26.7%, risk difference [RD] 11.6%, Confidence Interval [CI]
2.93% to 20.3%; adjusted odds ratio [OR] 1.7, CI 1.1 to 2.5). Patients reported
less illicit drug use (RD -6.0, CI -11 to -1.2; OR 0.52, CI 0.28 to 0.96), and
less risk for STI (RD -5.4, CI -11 to 0.2; OR 0.66, CI 0.46 to 0.96) at three
months in the intervention relative to the comparison arm, and for unplanned
pregnancy at 12 months (RD -4.4; CI -8.7 to -0.1; OR 0.40, CI 0.20 to 0.80). No
differences were detected between arms on other health risks. There were no
differences on secondary outcomes, apart from a greater detection of abuse (OR
13.8, CI 1.71 to 111). There were no reports of harmful events and intervention
arm youth had high acceptance of the screening tool. CONCLUSIONS: A complex
intervention, compared to a simple educational seminar for practices, improved
detection of health risk behaviours in young people. Impact on health outcomes
was inconclusive. Technology enabling more efficient, systematic health-risk
screening may allow providers to target counselling toward higher risk
individuals. Further trials require more power to confirm health benefits. TRIAL
REGISTRATION: ISRCTN.com ISRCTN16059206.
PMID- 26422236
TI - Cytologic and Immunophenotypic Features of Malignant Cells in Pediatric Body
Fluids.
AB - OBJECTIVE: Cytospin preparations and immunocytochemistry are common methods in
hospitals to evaluate malignancies in body fluids. Characteristics of malignant
cells in pediatric body fluids have not been adequately evaluated. STUDY DESIGN:
183 pleural, peritoneal and pericardial pediatric fluid specimens were examined
by cytospin preparations and immunocytochemistry from two hospitals using similar
procedural techniques. Cytologic diagnoses were correlated with the results of
clinical history, histology and ancillary studies. RESULTS: Forty cases with
malignancy were identified (21.9%); the most common diagnoses were
rhabdomyosarcoma and acute lymphoblastic lymphoma (9 and 8 cases, respectively).
Small round cell tumors revealed similar morphology as clusters of small round
cells with central nuclei and scant cytoplasm with frequent small vacuoles.
Twenty-one cases were evaluated by immunocytochemistry, 12 by flow cytometry and
5 by cytogenetic analysis. CD3, CD20, TdT, CD10, desmin and myogenin were the
most common markers. Staining artifacts causing interpretation difficulties were
noted in 5 cases that were resolved by molecular studies and deferral for
surgical specimens. CONCLUSIONS: Small round cell tumors are the most common
malignancies encountered in pediatric body fluids and share a nonspecific
morphology. Although immunocytochemistry is helpful to arrive at the correct
diagnosis, other ancillary studies may be necessary, particularly in hematologic
malignancies and other difficult cases.
PMID- 26422237
TI - Seasonal Preservation Success of the Marine Dinoflagellate Coral Symbiont,
Symbiodinium sp.
AB - Coral reefs are some of the most diverse and productive ecosystems on the planet,
but are threatened by global and local stressors, mandating the need for
incorporating ex situ conservation practices. One approach that is highly
protective is the development of genome resource banks that preserve the species
and its genetic diversity. A critical component of the reef are the endosymbiotic
algae, Symbiodinium sp., living within most coral that transfer energy-rich
sugars to their hosts. Although Symbiodinium are maintained alive in culture
collections around the world, the cryopreservation of these algae to prevent loss
and genetic drift is not well-defined. This study examined the quantum yield
physiology and freezing protocols that resulted in survival of Symbiodinium at 24
h post-thawing. Only the ultra-rapid procedure called vitrification resulted in
success whereas conventional slow freezing protocols did not. We determined that
success also depended on using a thin film of agar with embedded Symbiodinium on
Cryotops, a process that yielded a post-thaw viability of >50% in extracted and
vitrified Symbiodinium from Fungia scutaria, Pocillopora damicornis and Porites
compressa. Additionally, there also was a seasonal influence on vitrification
success as the best post-thaw survival of F. scutaria occurred in winter and
spring compared to summer and fall (P < 0.05). These findings lay the foundation
for developing a viable genome resource bank for the world's Symbiodinium that,
in turn, will not only protect this critical element of coral functionality but
serve as a resource for understanding the complexities of symbiosis, support
selective breeding experiments to develop more thermally resilient strains of
coral, and provide a 'gold-standard' genomics collection, allowing for full
genomic sequencing of unique Symbiodinium strains.
PMID- 26422238
TI - The effect of noninvasive brain stimulation on neural connectivity in Tinnitus: A
randomized trial.
AB - OBJECTIVES/HYPOTHESIS: To explore neural connectivity changes associated with
repetitive transcranial magnetic stimulation (rTMS) to the temporoparietal
junction for patients with bothersome tinnitus. STUDY DESIGN: Randomized, double
blind, controlled clinical trial. METHODS: Thirty patients with subjective,
nonpulsatile tinnitus for 6 months duration or longer and a score of 36 or
greater on the Tinnitus Handicap Inventory completed the study. Participants were
randomized to receive either sham or active treatment with rTMS to the
temporoparietal junction for either 2 or 4 weeks of therapy. Participants
underwent resting state functional connectivity magnetic resonance imaging before
therapy and immediately following treatment. Functional connectivity changes
between active and sham treatment groups were compared using regions of interest
in auditory, default mode, ventral attention, and executive attention networks.
RESULTS: Sixteen patients received active rTMS treatment; 14 patients received
sham treatment. There were no differences between the active and sham groups in
baseline functional connectivity. Neither treatment with rTMS nor sham therapy
resulted in statistically significant functional connectivity changes in the
examined brain networks. CONCLUSIONS: The analysis did not identify any changes
in neural connectivity following treatment in patients with bothersome tinnitus.
These results are consistent with our findings of lack of symptom changes
previously reported in the same group of patients. Measures of neural
connectivity may inform future work using rTMS to better understand the possible
benefits of neural stimulation for tinnitus. LEVEL OF EVIDENCE: 1b. Laryngoscope,
126:1201-1206, 2016.
PMID- 26422239
TI - Physical Functional Limitations among Aboriginal and Non-Aboriginal Older Adults:
Associations with Socio-Demographic Factors and Health.
AB - BACKGROUND: Australian Aboriginal people are disproportionately affected by
physical disability; the reasons for this are unclear. This study aimed to
quantify associations between severe physical functional limitations and socio
demographic and health-related factors among older Aboriginal and non-Aboriginal
adults. METHODS: Questionnaire data from 1,563 Aboriginal and 226,802 non
Aboriginal participants aged >=45 years from the Sax Institute's 45 and Up Study
(New South Wales, Australia) were used to calculate age- and sex-adjusted
prevalence ratios (aPRs) for severe limitation [MOS-PF score <60] according to
socio-demographic and health-related factors. RESULTS: Overall, 26% (410/1563) of
Aboriginal participants and 13% (29,569/226,802) of non-Aboriginal participants
had severe limitations (aPR 2.8, 95%CI 2.5-3.0). In both Aboriginal and non
Aboriginal participants, severe limitation was significantly associated with:
being >=70 vs <70 years old (aPRs 1.8, 1.3-2.4 and 5.3, 5.0-5.5, within
Aboriginal and non-Aboriginal participants, respectively), none vs tertiary
educational qualifications (aPRs 2.4, 1.7-3.3 and 3.1, 3.0-3.2), lower vs higher
income (aPRs 6.6, 4.2-10.5 and 5.5, 5.2-5.8), current vs never-smoking (aPRs 2.0,
1.6-2.5 and 2.2, 2.1-2.3), obese vs normal weight (aPRs 1.7, 1.3-2.2 and 2.7, 2.7
2.8) and sitting for >=7 vs <7 hours/day (aPRs 1.6, 1.2-2.0 and 1.6, 1.6-1.7).
Severe limitations increased with increasing ill-health, with aPRs rising to 5-6
for >=5 versus no chronic conditions. It was significantly higher in those with
few vs many social contacts (aPRs 1.7, 1.4-2.0 and 1.4, 1.4-1.4) and with very
high vs low psychological distress (aPRs 4.4, 3.6-5.4 and 5.7, 5.5-5.9).
CONCLUSIONS: Although the prevalence of severe physical limitation among
Aboriginal people in this study is around three-fold that of non-Aboriginal
people, the factors related to it are similar, indicating that Aboriginal people
have higher levels of risk factors for and consequences of severe limitations.
Effective management of chronic disease and reducing the prevalence of obesity
and smoking are important areas for attention.
PMID- 26422240
TI - Pyrocarbon Proximal Interphalangeal Joint Arthroplasty: Minimum Five-Year Follow
Up.
AB - PURPOSE: To report the outcomes, complications, and survivorship of pyrocarbon
proximal interphalangeal joint arthroplasty at a minimum of 5-year follow-up.
METHODS: A review of 97 implants in 72 consecutive patients from our joint
arthroplasty database was undertaken. Patient demographics, complications,
further surgery, and implant revision were recorded. Objective outcome was
assessed by grip strength, range of motion, and radiological assessment of
alignment, loosening, and subsidence. Subjective outcome was assessed by Patient
Evaluation Measure; Quick Disabilities of the Arm, Shoulder, and Hand score; and
visual analog scores (0, best; 10, worst) for appearance, satisfaction, and pain.
RESULTS: Diagnosis was osteoarthritis in 60 joints, rheumatoid arthritis in 12
joints, psoriatic arthritis in 11 joints, and trauma in 14 joints. The average
follow-up was 118 months (range, 60-164 months). The mean arc of motion was 35
degrees (range, 0 degrees to 90 degrees ). There was no difference in grip
strength between operated and nonoperated side. Of the 97 implants, 36 required
additional surgery, of which 14 were revised and 22 required reconstruction
around a retained implant. The average Patient Evaluation Measure and Quick
Disabilities of the Arm, Shoulder and Hand scores were 33 (range, 10-69) and 35
(range, 0-93), respectively. Mean visual analog scores for pain, satisfaction,
and appearance were 2 (range, 0-8), 7 (0-10), and 8 (0-10), respectively. All
implants had a lucent line with nearly all classified as either Herren grade 2 or
3. Progressive loosening was seen in 48% of implants. Implant survival as
assessed by Kaplan-Meier was 85% at both 5 and 10 years. CONCLUSIONS: Good pain
relief and maintenance of preoperative arc of motion was achieved with no major
deterioration over time. Most implant revisions were performed within 24 months
of the index procedure. Currently progressive loosening was not translated into
revision surgery. Implant revision rate was higher than with other prostheses.
TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 26422242
TI - Chronic Disease Prevalence and Healthy Lifestyle Behaviors Among US Health Care
Professionals.
AB - Although health care professionals may be assumed to make healthier lifestyle
choices and have better health outcomes than others because of their greater
health literacy, little is known about how actual health outcomes of health care
professionals compare with those of the overall population. We analyzed how
trends in obesity, diabetes, hypertension, and coronary artery disease prevalence
as well as several health behaviors (smoking, alcohol use, and exercise) varied
between health care professionals and the general US population from 2002 to
2013, using nationally representative data collected by the National Health
Interview Survey. We estimated multivariate logistic regressions of each disease
and behavior adjusted for age, race, sex, geographic region, and year. Although
rates of obesity, diabetes, and hypertension were lower among health care
professionals compared with the overall population, disease was still common
among health care professionals and increased over time at a rate similar to that
of the overall population. For example, obesity prevalence was lower among health
care professionals but increased similarly from 2002 to 2013 (health care
professionals, 20.5% in 2002 to 22.1% in 2013; other occupations, 28.4% to 31.7%;
P=.64 for difference in trend). Diabetes prevalence was modestly lower among
health care professionals but increased at a similar rate (health care
professionals, 7.4% in 2005 to 8.6% in 2013; other occupations, 8.7% to 9.9%;
P=.67 for difference in trend). Similar patterns were noted in hypertension.
Coronary artery disease prevalence declined over time among health care
professionals but increased for others. Health care professionals reported better
health behaviors than others in smoking and physical activity but not in moderate
to heavy alcohol use.
PMID- 26422243
TI - Standing, Obesity, and Metabolic Syndrome: Findings From the Cooper Center
Longitudinal Study.
AB - OBJECTIVE: To examine the cross-sectional relationships between standing time,
obesity, and metabolic syndrome alongside and independent of leisure-time
physical activity (LTPA). PARTICIPANTS AND METHODS: The primary study sample
consisted of 7075 adult patients (aged 20-79 years) from Cooper Clinic (Dallas,
Texas). In this cross-sectional study we assessed the associations between
reported standing time and directly measured obesity (body mass index >= 30),
elevated waist circumference (men: >= 102 cm; women: >= 88 cm), body fat
percentage (men: >= 25%; women >= 30%), and metabolic syndrome (yes/no). In
addition, the joint associations of standing and LTPA on each outcome were
examined. Multivariable logistic regression adjusting for confounders was used
for statistical analyses. RESULTS: Standing a quarter of the time or more was
significantly associated with reduced odds of an elevated body fat percentage in
men (P < .001) and a reduced likelihood of obesity (P < .009) and abdominal
obesity (P=.04) in women. In addition, joint association analyses indicated that
compared with the reference group (ie, not meeting the physical activity
guidelines/standing almost none of the time), men and women who met the physical
activity guidelines had lower odds of all obesity outcomes and metabolic syndrome
with incremental additions of standing time (ie, a dose-response relationship).
CONCLUSION: Standing a quarter of the time per day or more is associated with
reduced odds of obesity. The inverse relationship of standing to obesity and
metabolic syndrome is more robust when combined with health-promoting LTPA.
Prospective studies are warranted to confirm these findings and establish a
causal relationship.
PMID- 26422241
TI - Loss of Hif-2alpha Rescues the Hif-1alpha Deletion Phenotype of Neonatal
Respiratory Distress In Mice.
AB - Hypoxia is a state of decreased oxygen reaching the tissues of the body. During
prenatal development, the fetus experiences localized occurrences of hypoxia that
are essential for proper organogenesis and survival. The response to decreased
oxygen availability is primarily regulated by hypoxia-inducible factors (HIFs), a
family of transcription factors that modulate the expression of key genes
involved in glycolysis, angiogenesis, and erythropoiesis. HIF-1alpha and HIF
2alpha, two key isoforms, are important in embryonic development, and likely are
involved in lung morphogenesis. We have recently shown that the inducible loss of
Hif-1alpha in lung epithelium starting at E4.5 leads to death within an hour of
parturition, with symptoms similar to neonatal respiratory distress syndrome
(RDS). In addition to Hif-1alpha, Hif-2alpha is also expressed in the developing
lung, although the overlapping roles of Hif-1alpha and Hif-2alpha in this context
are not fully understood. To further investigate the independent role of Hif
2alpha in lung epithelium and its ability to alter Hif-1alpha-mediated lung
maturation, we generated two additional lung-specific inducible Hif-alpha
knockout models (Hif-2alpha and Hif-1alpha+Hif-2alpha). The intrauterine loss of
Hif-2alpha in the lungs does not lead to decreased viability or observable
phenotypic changes in the lung. More interestingly, survivability observed after
the loss of both Hif-1alpha and Hif-2alpha suggests that the loss of Hif-2alpha
is capable of rescuing the neonatal RDS phenotype seen in Hif-1alpha-deficient
pups. Microarray analyses of lung tissue from these three genotypes identified
several factors, such as Scd1, Retlngamma, and Il-1r2, which are differentially
regulated by the two HIF-alpha isoforms. Moreover, network analysis suggests that
modulation of hormone-mediated, NF-kappaB, C/EBPalpha, and c-MYC signaling are
central to HIF-mediated changes in lung development.
PMID- 26422244
TI - Less Sitting, More Physical Activity, or Higher Fitness?
AB - Epidemiological studies have found that time spent in sedentary behaviors, levels
of physical activity, and cardiorespiratory fitness are all associated with
mortality rates. They are also related to the risks of obesity, type 2 diabetes
mellitus, hypertension, cardiovascular disease, aging-associated frailty, and
cancer. The evidence is such that the National Institutes of Health recently
launched a new Common Fund initiative aimed at identifying the molecular
transducers of adaptation to physical activity in various tissues and organs. It
has been estimated that 9.4% of all 57 million deaths in the world in 2008 could
be attributed to physical inactivity, which translates into more than 5 million
deaths worldwide. Physical inactivity has a deleterious effect that is comparable
to smoking and obesity. Importantly, this global estimate relates to levels of
physical activity and does not take into account sedentary behavior and
cardiorespiratory fitness. Currently, there are national and international
guidelines for physical activity level that are highly concordant. The weekly
recommendations include 150 minutes of moderate-intensity activity, 75 minutes of
vigorous-intensity activity, or some combination of moderate and vigorous
activity with 2 days of resistance exercise. However, these guidelines offer no
recommendations regarding sedentary time or goals for cardiorespiratory fitness
levels. It will be increasingly important for disease prevention, successful
aging, and reduction of premature mortality to broaden the focus of the public
health message to include not only more physical activity but also less sitting
and higher cardiorespiratory fitness. We briefly review the evidence and discuss
key issues to be addressed to make this approach a reality.
PMID- 26422245
TI - Synthesis of Triazole Schiff's Base Derivatives and Their Inhibitory Kinetics on
Tyrosinase Activity.
AB - In the present study, new Schiff's base derivatives: (Z)-4-amino-5-(2-(3-
fluorobenzylidene)hydrazinyl)-4H-1,2,4-triazole-3-thiol (Y1), (Z)-3-((2-(4-amino
5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y2), (Z)-2-((2-(4
amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y3) and 3-((Z)
(2-(4- (((E)-3-hydroxybenzylidene)amino)-5-mercapto-4H-1,2,4-triazol-3
yl)hydrazono)methyl)phenol (Y4) were synthesized and their structures were
characterized by LC-MS, IR and 1H NMR. The inhibitory effects of these compounds
on tyrosinase activites were evaluated. Compounds Y1, Y2 and Y3 showed potent
inhibitory effects with respective IC50 value of 12.5, 7.0 and 1.5 MUM on the
diphenolase activities. Moreover, the inhibition mechanisms were determined to be
reversible and mixed types. Interactions of the compounds with tyrosinase were
further analyzed by fluorescence quenching, copper interaction, and molecular
simulation assays. The results together with the anti-tyrosinase activities data
indicated that substitution on the second position of benzene ring showed
superior ant-ityrosinase activities than that on third position, and that
hydroxyl substitutes were better than fluorine substitutes. In addition, two
benzene rings connecting to the triazole ring would produce larger steric
hindrance, and affect the bonding between tyrosinase and inhibitors to decrease
the inhibitory effects. The anti-tyrosinase effects of these compounds were in
contrast to their antioxidant activities. In summary, this research will
contribute to the development and design of antityrosinase agents.
PMID- 26422246
TI - Pneumocystis Pneumonia in Patients with Autoimmune Diseases: A Retrospective
Study Focused on Clinical Characteristics and Prognostic Factors Related to
Death.
AB - BACKGROUND: With the increasing use of immunosuppressive agents, the number of
opportunistic infections has risen in patients with autoimmune diseases.
Pneumocystis pneumonia (PCP) is one of these opportunistic infections that have a
high mortality rate. However, only a few studies have described PCP in these
patients, and these studies are limited in scope. We conducted this retrospective
study to describe the clinical characteristics and factors associated with
outcomes of PCP in patients with autoimmune diseases. METHODS: A retrospective
study was performed in laboratory diagnosed PCP patients with autoimmune diseases
in an academic hospital over a 10-year period. Patients with human
immunodeficiency virus (HIV) infection were not included. Clinical
characteristics were collected and the factors related to death were analysed.
RESULTS: A total of 69 patients with PCP during the study period were included.
Common clinical features included fever (81%), cough (56%), and dyspnea (35%).
Ground glass opacity (81%) and reticulation (52%) were the most common
radiological findings. Concurrent pulmonary infections including bacterium,
aspergillus and cytomegalovirus were found in 34% of the patients. The overall in
hospital mortality rate was 32%. High mortality was associated with lower
PaO2/FiO2 ratios and albumin levels. The lymphocyte count, CD4+ T cell count,
previous usage of immunosuppressive agents, the duration and dose of
glucocorticoids did not affect the outcome. CONCLUSIONS: The mortality rate in
PCP patients with autoimmune diseases is high. Low PaO2/FiO2 ratios and albumin
levels are independent prognostic factors of mortality.
PMID- 26422248
TI - Determinants of False-Negative Fine-Needle Aspirates of Axillary Lymph Nodes in
Women with Breast Cancer: Lymph Node Size, Cortical Thickness and Hilar Fat
Retention.
AB - OBJECTIVE: Ultrasound-guided fine-needle aspiration (UG-FNA) is utilized to
sample axillary lymph nodes in breast cancer patients. Diagnostic sensitivity is
good but few data exist regarding the causes of false-negative results. STUDY
DESIGN: Fifty-four UG-FNAs of sentinel lymph nodes with histologic follow-up were
identified. Gross and radiographic lymph node size, the percentage replaced by
carcinoma and the cortical thickness were correlated with false-negative rates.
RESULTS: Thirty-seven aspirates were negative, 5 of these being false-negative
(9%). True-positive lymph nodes averaged 1.3 cm in dimension while false
negatives averaged 0.92 cm. Percentage involvement by carcinoma for true-positive
FNAs averaged 69% while false-negatives averaged 25%. Cortical thickness averaged
5.6 mm in true-positive FNAs but 2.9 mm in false-negatives. CONCLUSION: A
relationship exists between lymph node size and the likelihood of a false
negative FNA. Lymph nodes <1.2 cm have a higher incidence of false-negative
results. Lymph nodes with <30% involvement demonstrated a higher percentage of
false-negatives than those with >30% replacement. Sentinel lymph nodes <1 cm
appear to be relatively poor candidates for UG-FNA. Lymph nodes with a cortical
thickness <3.5 mm are more often associated with a false-negative result than
nodes with a thicker cortex.
PMID- 26422247
TI - Human Polyclonal Antibodies Produced through DNA Vaccination of Transchromosomal
Cattle Provide Mice with Post-Exposure Protection against Lethal Zaire and Sudan
Ebolaviruses.
AB - DNA vaccination of transchromosomal bovines (TcBs) with DNA vaccines expressing
the codon-optimized (co) glycoprotein (GP) genes of Ebola virus (EBOV) and Sudan
virus (SUDV) produce fully human polyclonal antibodies (pAbs) that recognize both
viruses and demonstrate robust neutralizing activity. Each TcB was vaccinated by
intramuscular electroporation (IM-EP) a total of four times and at each
administration received 10 mg of the EBOV-GPco DNA vaccine and 10 mg of the SUDV
GPco DNA vaccine at two sites on the left and right sides, respectively. After
two vaccinations, robust antibody responses (titers > 1000) were detected by
ELISA against whole irradiated EBOV or SUDV and recombinant EBOV-GP or SUDV-GP
(rGP) antigens, with higher titers observed for the rGP antigens. Strong, virus
neutralizing antibody responses (titers >1000) were detected after three
vaccinations when measured by vesicular stomatitis virus-based pseudovirion
neutralization assay (PsVNA). Maximal neutralizing antibody responses were
identified by traditional plaque reduction neutralization tests (PRNT) after four
vaccinations. Neutralizing activity of human immunoglobulins (IgG) purified from
TcB plasma collected after three vaccinations and injected intraperitoneally (IP)
into mice at a 100 mg/kg dose was detected in the serum by PsVNA up to 14 days
after administration. Passive transfer by IP injection of the purified IgG (100
mg/kg) to groups of BALB/c mice one day after IP challenge with mouse adapted
(ma) EBOV resulted in 80% protection while all mice treated with non-specific
pAbs succumbed. Similarly, interferon receptor 1 knockout (IFNAR(-/-)) mice
receiving the purified IgG (100 mg/kg) by IP injection one day after IP challenge
with wild type SUDV resulted in 89% survival. These results are the first to
demonstrate that filovirus GP DNA vaccines administered to TcBs by IM-EP can
elicit neutralizing antibodies that provide post-exposure protection.
Additionally, these data describe production of fully human IgG in a large animal
system, a system which is capable of producing large quantities of a clinical
grade therapeutic product.
PMID- 26422249
TI - Design and Development of Micro-Power Generating Device for Biomedical
Applications of Lab-on-a-Disc.
AB - The development of micro-power generators for centrifugal microfluidic discs
enhances the platform as a green point-of-care diagnostic system and eliminates
the need for attaching external peripherals to the disc. In this work, we present
micro-power generators that harvest energy from the disc's rotational movement to
power biomedical applications on the disc. To implement these ideas, we developed
two types of micro-power generators using piezoelectric films and an
electromagnetic induction system. The piezoelectric-based generator takes
advantage of the film's vibration during the disc's rotational motion, whereas
the electromagnetic induction-based generator operates on the principle of
current generation in stacks of coil exposed to varying magnetic flux. We have
successfully demonstrated that at the spinning speed of 800 revolutions per
minute (RPM) the piezoelectric film-based generator is able to produce up to 24
microwatts using 6 sets of films and the magnetic induction-based generator is
capable of producing up to 125 milliwatts using 6 stacks of coil. As a proof of
concept, a custom made localized heating system was constructed to test the
capability of the magnetic induction-based generator. The heating system was able
to achieve a temperature of 58.62 degrees C at 2200 RPM. This development of lab
on-a-disc micro power generators preserves the portability standards and enhances
the future biomedical applications of centrifugal microfluidic platforms.
PMID- 26422250
TI - The Role of beta-Catenin in Bcr/Abl Negative Myeloproliferative Neoplasms: An
Immunohistochemical Study.
AB - INTRODUCTION: beta-Catenin is a multifunctional protein that acts as a central
effector molecule in the Wnt signaling pathway. Aberrant activation of the
Wnt/beta-catenin signaling pathway causes various diseases including cancer. In
this study we evaluated beta-catenin expression in bcr/abl-negative
myeloproliferative neoplasms (MPNs). MATERIALS AND METHODS: The expression of
beta-catenin was evaluated in bone marrow using immunohistochemical methods in 66
patients with bcr/abl-negative myeloproliferative neoplasms (MPNs) and in 30
healthy control subjects. Immunreactive score (IRS; staining intensity *
percentage of positive stained cells) was used for the evaluation of the cell
staining reaction. RESULTS: IRS of megakaryocytes (IRSmega) was higher in
essential thrombocytemia (ET) compared with the control group (P = .022) and
primary myelofibrosis (PMF; P = .001). IRS of vascular endothelial cells (IRSvas)
was higher in the bcr/abl negative MPN compared with the control group (P =
.024). Also, IRSvas was higher in the PMF compared with the control group (P =
.001), policythemia vera (PV; P = .005), and ET (P = .006). A positive
correlation was detected between IRSmega and platelet counts (P = .019).
CONCLUSION: Results of this study suggest that the Wnt/beta-catenin signaling
pathway has a role in the angiogenesis of PMF and in the thrombopoiesis of PV and
ET. Hence, targeting the Wnt/beta-catenin signaling pathway could open new
avenues for novel therapeutic approaches in bcr/abl-negative MPNs.
PMID- 26422251
TI - Impact of Alemtuzumab Therapy and Route of Administration in T-Prolymphocytic
Leukemia: A Single-Center Experience.
AB - OBJECTIVE: We conducted a single-center retrospective analysis to determine the
impact of the anti-CD52 monoclonal antibody alemtuzumab including route of
administration compared to non-alemtuzumab-containing regimens in T
prolymphocytic leukemia (T-PLL). PATIENTS AND METHODS: The study was a
retrospective analysis of a consecutive cohort of adult patients diagnosed with T
PLL at Mayo Clinic Rochester from January 1, 1997, through September 30, 2014.
RESULTS: A total of 41 patients were diagnosed with T-PLL per the World Health
Organization 2008 classification. The median age was 66 years, and 23 (56%) were
male. After a median follow-up of 18 months (range, 0.4-66.1 months), 32 patients
(78%) had died, with a median overall survival of 16.9 months. Approximately half
the cohort was treated with alemtuzumab, almost exclusively after 2004. Median
survival for patients receiving intravenous alemtuzumab-based therapy was 40.5
versus 10.3 months for all other therapies (P = .0004). A significant survival
difference between intravenous versus subcutaneous alemtuzumab administration of
40.5 versus 13.7 months was noted (P = .0014). Only 4 (14%) of 28 patients aged <
70 years underwent hematopoietic stem cell transplantation, with a median
survival after transplantation of 4 months. CONCLUSION: In this large series of T
PLL patients treated at a single tertiary-care center, we confirmed the prior
observation of the superiority of intravenous alemtuzumab over other therapies.
Hematopoietic stem cell transplantation was feasible in a minority of potentially
eligible patients. Early transplant referral should be considered for all
eligible patients.
PMID- 26422253
TI - Unclassified bleeding disorders: outcome of haemostatic challenges following
tranexamic acid and/or desmopressin.
AB - INTRODUCTION: In a minority of patients with a significant bleeding history no
cause is found despite extensive testing and we diagnose such cases as
unclassified bleeding disorders (UBD). UBDs may have diverse underlying causes
and currently no standard management strategy exists in the event of a
haemorrhage or to cover surgery. AIM: To document the clinical characteristics
and response to treatment of UBDs. METHODS: We performed a retrospective chart
review of all patients with UBDs who had an invasive procedure at our centre
between 1998 and 2014. RESULTS: The commonest symptoms were menorrhagia (89%) and
bleeding at the time of surgery (88%) or dental extraction (85%). A total of 33
patients underwent 78 minor and major haemostatic challenges. Haemostatic cover
was provided in 28 procedures with tranexamic acid alone, two with desmopressin
and 45 with both agents in combination. A successful haemostatic outcome was
observed in 70/78 (90%) cases. No patient required additional surgical
intervention to achieve haemostasis, but one patient required a platelet
transfusion to control postoperative bleeding. CONCLUSIONS: This is the first
study to report on the investigation and treatment of UBD. Future studies are
needed to further our understanding of the bleeding phenotype and identify any
underlying causes.
PMID- 26422252
TI - Treatment of Patients With Myelodysplastic Syndrome With Lenalidomide in Clinical
Routine in Austria.
AB - BACKGROUND: Lenalidomide has demonstrated remarkable efficacy for therapy of
lower-risk myelodysplastic syndromes (MDS) associated with 5q(-). The present
evaluation aimed to describe the characteristics and outcomes of low-risk MDS
patients treated with lenalidomide in Austria. PATIENTS AND METHODS: For this
retrospective, multicenter, observational analysis of MDS patients who received
lenalidomide, data were collected at various hospitals in Austria over a period
of 3 years. MDS classification, previous and current MDS therapies, and outcome
and safety of lenalidomide were evaluated. RESULTS: Forty-six percent of the
patients (n = 23) had a 5q(-) syndrome, while 12% (n = 6) exhibited 5q(-) plus
additional aberrations or isolated 5q(-) but >= 5% blasts in the bone marrow
(10%, n = 5). The remaining 32% of patients (n = 16) had MDS with other World
Health Organization classifications. Seventy percent belonged to lower
International Prognostic Scoring System risk classes. Sixteen centers
participated, involving a total of 50 patients. Most frequently used lenalidomide
doses were 10 mg and 5 mg on days 1 to 21 of a 28-day cycle. Seventy-five percent
of the patients received 11 months of treatment, with a median therapy period of
3.5 months; median follow-up was 3.9 months (range, 0-26 months). Response rate,
defined as transfusion independence during the 2 months after lenalidomide
therapy, was 64%. Median overall survival was not reached. CONCLUSION:
Lenalidomide was well tolerated and is an effective and well-tolerated option for
therapy of patients with 5q(-) syndrome but also lower-risk MDS patients with
other World Health Organization classifications in clinical practice.
PMID- 26422255
TI - Dependency of Phytoprostane Fingerprints of Must and Wine on Viticulture and
Enological Processes.
AB - Wine is one of the most consumed alcoholic beverages around the world. Red wine
has demonstrated several benefits for health maintenance. One group of potential
anti-inflammatory compounds is the phytoprostanes, oxidative degradation products
of linolenic acid. The aim of the present study was to measure, for the first
time, the phytoprostane content in wine and must by an UHPLC-QqQ-MS/MS method
after solid-phase extraction. The data showed two predominant classes of
phytoprostanes: F1- and D1-phytoprostane series. In wines, the total
phytoprostane concentration ranged from 134.1 +/- 2.3 to 216.2 +/- 3.06 ng/mL.
Musts showed concentrations between 21.4 +/- 0.8 and 447.1 +/- 15.8 ng/mL. The
vinification and aging procedures for the production of wine seem to influence
the final phytoprostane levels in red wine and to modify the phytoprostane
profile. The high concentrations observed and previous reports on anti
inflammatory effects of phytoprostanes make further research on the benefits of
phytoprostanes more important.
PMID- 26422254
TI - Hemorrhage Exacerbates Radiation Effects on Survival, Leukocytopenia,
Thrombopenia, Erythropenia, Bone Marrow Cell Depletion and Hematopoiesis, and
Inflammation-Associated microRNAs Expression in Kidney.
AB - Exposure to high-dose radiation results in detrimental effects on survival. The
effects of combined trauma, such as radiation in combination with hemorrhage, the
typical injury of victims exposed to a radiation blast, on survival and
hematopoietic effects have yet to be understood. The purpose of this study was to
evaluate the effects of radiation injury (RI) combined with hemorrhage (i.e.,
combined injury, CI) on survival and hematopoietic effects, and to investigate
whether hemorrhage (Hemo) enhanced RI-induced mortality and hematopoietic
syndrome. Male CD2F1 mice (10 weeks old) were given one single exposure of gamma-
radiation (60Co) at various doses (0.6 Gy/min). Within 2 hr after RI, animals
under anesthesia were bled 0% (Sham) or 20% (Hemo) of total blood volume via the
submandibular vein. In these mice, Hemo reduced the LD50/30 for 30-day survival
from 9.1 Gy (RI) to 8.75 Gy (CI) with a DMF of 1.046. RI resulted in
leukocytopenia, thrombopenia, erythropenia, and bone marrow cell depletion, but
decreased the caspase-3 activation response. RI increased IL-1beta, IL-6, IL-17A,
and TNF-alpha concentrations in serum, bone marrow, ileum, spleen, and kidney.
Some of these adverse alterations were magnified by CI. Erythropoietin production
was increased in kidney and blood more after CI than RI. Furthermore, CI altered
the global miRNAs expression in kidney and the ingenuity pathway analysis showed
that miRNAs viz., let-7e, miR-30e and miR-29b that were associated with
hematopoiesis and inflammation. This study provides preliminary evidence that non
lethal Hemo exacerbates RI-induced mortality and cell losses associated with high
dose gamma-radiation. We identified some of the initial changes occurring due to
CI which may have facilitated in worsening the injury and hampering the recovery
of animals ultimately resulting in higher mortality.
PMID- 26422256
TI - RF inhomogeneity and how it controls CPMAS.
AB - In this report we discuss the effect of radiofrequency field (RF) inhomogeneity
on cross-polarization (CP) under magic-angle spinning (MAS) by reviewing the
dependence of the CP-detected signal intensity as a function of the position in
the sample space. We introduce a power-function model to quantify the position
dependent RF-amplitude profile. The applicability of this model is experimentally
verified by nutation spectra obtained by direct signal detection, as well as by
CPMAS signal detection, in two commercial MAS probes with different degrees of RF
inhomogeneity. A conclusion is that substantial sections of a totally filled
rotor, even in a probe with rather good homogeneity, do not contribute at all to
the detected spectra. The consequence is that in CPMAS-based recoupling
experiments, such as the CP-with-variable-contact-time (CPVC), spatial
selectivity of the Hartmann-Hahn matching condition overcomes complications that
could be caused by RF inhomogeneity permitting determination of accurate spectral
parameters even in cases with high inhomogeneity.
PMID- 26422257
TI - Methionine bound to Pd/gamma-Al2O3 catalysts studied by solid-state (13)C NMR.
AB - The chemisorption and breakdown of methionine (Met) adsorbed on Pd/gamma-Al2O3
catalysts were investigated by solid-state NMR. (13)C-enriched Met (ca. 0.4mg)
impregnated onto gamma-Al2O3 or Pd/gamma-Al2O3 gives NMR spectra with
characteristic features of binding to gamma-Al2O3, to Pd nanoparticles, and
oxidative or reductive breakdown of Met. The SCH3 groups of Met showed
characteristic changes in chemical shift on gamma-Al2O3 (13ppm) vs. Pd (19ppm),
providing strong evidence for preferential binding to Pd, while the NC carbon
generates a small resonance at 96ppm assigned to a distinct nonprotonated species
bound to O or Pd. Additionally, NMR shows that the SCH3 groups of Met are mobile
on gamma-Al2O3 but immobilized by binding to Pd particles; on small Pd particles
(ca. 4nm), the NCH groups undergo large-amplitude motions. In a reducing
environment, Met breaks down by C-S bond cleavage followed by formation of C2-C4
organic acids. The SCH3 signal shifts to 22ppm, which is likely the signature of
the principal species responsible for strong catalyst inhibition. These
experiments demonstrate that solid-state magic-angle spinning NMR of (13)C
enriched Met can be a sensitive probe to investigate catalyst surfaces and
characterize catalyst inhibition both before reaction and postmortem.
PMID- 26422258
TI - Oseltamivir Resistance in Influenza A(H6N2) Caused by an R292K Substitution in
Neuraminidase Is Not Maintained in Mallards without Drug Pressure.
AB - BACKGROUND: Wild waterfowl is the natural reservoir of influenza A virus (IAV);
hosted viruses are very variable and provide a source for genetic segments which
can reassort with poultry or mammalian adapted IAVs to generate novel species
crossing viruses. Additionally, wild waterfowl act as a reservoir for highly
pathogenic IAVs. Exposure of wild birds to the antiviral drug oseltamivir may
occur in the environment as its active metabolite can be released from sewage
treatment plants to river water. Resistance to oseltamivir, or to other
neuraminidase inhibitors (NAIs), in IAVs of wild waterfowl has not been
extensively studied. AIM AND METHODS: In a previous in vivo Mallard experiment,
an influenza A(H6N2) virus developed oseltamivir resistance by the R292K
substitution in the neuraminidase (NA), when the birds were exposed to
oseltamivir. In this study we tested if the resistance could be maintained in
Mallards without drug exposure. Three variants of resistant H6N2/R292K virus were
each propagated during 17 days in five successive pairs of naive Mallards, while
oseltamivir exposure was decreased and removed. Daily fecal samples were analyzed
for viral presence, genotype and phenotype. RESULTS AND CONCLUSION: Within three
days without drug exposure no resistant viruses could be detected by NA
sequencing, which was confirmed by functional NAI sensitivity testing. We
conclude that this resistant N2 virus could not compete in fitness with wild type
subpopulations without oseltamivir drug pressure, and thus has no potential to
circulate among wild birds. The results of this study contrast to previous
observations of drug induced resistance in an avian H1N1 virus, which was
maintained also without drug exposure in Mallards. Experimental observations on
persistence of NAI resistance in avian IAVs resemble NAI resistance seen in human
IAVs, in which resistant N2 subtypes do not circulate, while N1 subtypes with
permissive mutations can circulate without drug pressure. We speculate that the
phylogenetic group N1 NAs may easier compensate for NAI resistance than group N2
NAs, though further studies are needed to confirm such conclusions.
PMID- 26422259
TI - The Cost-Effectiveness of Emergency Hormonal Contraception with Ulipristal
Acetate versus Levonorgestrel for Minors in France.
AB - OBJECTIVE: To evaluate the cost-effectiveness of ulipristal acetate and
levonorgestrel in minors in France, and analyze whether it is worthwhile to
provide ulipristal acetate to minors free of charge. METHODS: The cost
effectiveness of two emergency contraceptive methods was compared based on a
decision-analytical model. Pregnancy rates, outcomes of unintended pregnancies,
and resource utilization were derived from the literature. Resources and their
costs were considered until termination or a few days after delivery.
Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The
cost of an unintended pregnancy in a French minor is estimated to be 1,630 ?
(range 1,330 ? - 1,803 ?). Almost 4 million ? (3.1 ? - 13.7 ? million) in
unintended pregnancy spending in 2010 could have been saved by the use of
ulipristal acetate instead of levonorgestrel. The incremental cost of ulipristal
acetate compared to levonorgestrel is 3.30 ? per intake, or 418 ? per pregnancy
avoided (intake within 72 hours). In the intake within 24 hours subgroup,
ulipristal acetate was found to be more efficacious at a lower cost compared to
levonorgestrel. CONCLUSIONS: Ulipristal acetate dominates levonorgestrel when
taken within 24 hours after unprotected intercourse, i.e., it is more effective
at a lower cost. When taken within 72 hours, ulipristal acetate is a cost-
effective alternative to levonorgestrel, given that the cost of avoiding an
additional pregnancy with ulipristal acetate is less than the average cost of
these pregnancies. In the light of these findings, it is worthwhile to provide
free access to minors.
PMID- 26422261
TI - Modeling conformational redox-switch modulation of human succinic semialdehyde
dehydrogenase.
AB - Succinic semialdehyde dehydrogenase (SSADH) converts succinic semialdehyde (SSA)
to succinic acid in the mitochondrial matrix and is involved in the metabolism of
the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The molecular
structure of human SSADH revealed the intrinsic regulatory mechanism--redox
switch modulation--by which large conformational changes are brought about in the
catalytic loop through disulfide bonding. The crystal structures revealed two
SSADH conformations, and computational modeling of transformation between them
can provide substantial insights into detailed dynamic redox modulation. On the
basis of these two clear crystal structures, we modeled the conformational motion
between these structures in silico. For that purpose, we proposed and used a
geometry-based coarse-grained mathematical model of long-range protein motion and
the related modeling algorithm. The algorithm is based on solving the special
optimization problem, which is similar to the classical Monge-Kantorovich mass
transportation problem. The modeled transformation was supported by another
morphing method based on a completely different framework. The result of the
modeling facilitates better interpretation and understanding of the SSADH
biological role.
PMID- 26422260
TI - Bird Richness and Abundance in Response to Urban Form in a Latin American City:
Valdivia, Chile as a Case Study.
AB - There is mounting evidence that urban areas influence biodiversity.
Generalizations however require that multiple urban areas on multiple continents
be examined. Here we evaluated the role of urban areas on avian diversity for a
South American city, allowing us to examine the effects of urban features common
worldwide, using the city of Valdivia, Chile as case study. We assessed the
number of birds and their relative abundance in 152 grid cells of equal size (250
m2) distributed across the city. We estimated nine independent variables: land
cover diversity (DC), building density (BD), impervious surface (IS),municipal
green space (MG),non-municipal green space (NG), domestic garden space (DG),
distance to the periphery (DP), social welfare index (SW), and vegetation
diversity (RV). Impervious surface represent 41.8% of the study area, while
municipal green, non-municipal green and domestic garden represent 11.6%, 23.6%
and 16% of the non- man made surface. Exotic vegetation species represent 74.6%
of the total species identified across the city. We found 32 bird species, all
native with the exception of House Sparrow and Rock Pigeon. The most common
species were House Sparrow and Chilean Swallow. Total bird richness responds
negatively to IS and MG, while native bird richness responds positively to NG and
negatively to BD, IS DG and, RV. Total abundance increase in areas with higher
values of DC and BD, and decrease in areas of higher values of IS, SW and VR.
Native bird abundance responds positively to NG and negatively to BD, IS MG, DG
and RV. Our results suggest that not all the general patterns described in
previous studies, conducted mainly in the USA, Europe, and Australia, can be
applied to Latin American cities, having important implications for urban
planning. Conservation efforts should focus on non-municipal areas, which harbor
higher bird diversity, while municipal green areas need to be improved to include
elements that can enhance habitat quality for birds and other species. These
findings are relevant for urban planning in where both types of green space need
to be considered, especially non-municipal green areas, which includes wetlands,
today critically threatened by urban development.
PMID- 26422262
TI - Using Multitouch Collaboration Technology to Enhance Social Interaction of
Children with High-Functioning Autism.
AB - AIMS: Children with high-functioning Autism Spectrum Disorder (HFASD) have major
difficulties in social communication skills, which may impact their performance
and participation in everyday life. The goal of this study was to examine whether
the StoryTable, an intervention paradigm based on a collaborative narrative,
multitouch tabletop interface, enhanced social interaction for children with
HFASD, and to determine whether the acquired abilities were transferred to
behaviors during other tasks. METHODS: Fourteen boys with HFASD, aged 7-12 years,
participated in a 3-week, 11-session intervention. Social interactions during two
nonintervention tasks were videotaped at three points in time, one prior to the
intervention (pre), a second immediately following the intervention (post) and a
third three weeks after the intervention (follow-up). The video-recorded files
were coded using the Friendship Observation Scale to ascertain the frequencies of
positive and negative social interactions and collaborative play. Differences in
these behaviors were tested for significance using nonparametric statistical
tests. RESULTS: There were significantly higher rates of positive social
interactions and collaborative play, and lower rates of negative social
interactions following the intervention suggesting generalization of the social
skills learned during the intervention. Improvement was maintained when tested
three weeks later. CONCLUSION: These findings provide support for the use of
collaborative technology-based interventions within educational settings to
enhance social interaction of children with HFASD.
PMID- 26422263
TI - A Content Analysis of Organ Donation Stories Printed in U.S. Newspapers:
Application of Newsworthiness.
AB - The current study applied a theory of newsworthiness to the topic of organ
donation. Specifically, content analysis of newspaper stories published in the
United States (N = 1,988) was performed to identify whether deviance and
significance of a story predicted story prominence, measured as story length and
placement in the newspaper. Results indicated support for study hypotheses:
Longer stories and front-page stories pertaining to organ donation were more
deviant and more significant in content. Analyses also indicated stories more
negative in nature were more likely given front-page coverage, represented
international events, and were high on deviance and significance. Higher
circulating newspapers were more likely to publish stories recounting negative
events in organ donation. Results indicated organ donation coverage represents a
valid application of newsworthiness theory, and implications of study findings
are discussed in relation to the agenda-setting function of news stories.
PMID- 26422264
TI - Aqueous Emulsion Droplets Stabilized by Lipid Vesicles as Microcompartments for
Biomimetic Mineralization.
AB - Mineral deposition within living cells relies on control over the distribution
and availability of precursors as well as the location and rates of nucleation
and growth. This control is provided in large part by biomolecular chelators,
which bind precursors and regulate their availability, and compartmentalization
within specialized mineralizing vesicles. Biomimetic mineralization in self
assembled lipid vesicles is an attractive means of studying the mineralization
process, but has proven challenging due to vesicle heterogeneity in lamellarity,
contents, and size across a population, difficulties encapsulating high and
uniform precursor concentrations, and the need to transport reagents across an
intact lipid bilayer membrane. Here, we report the use of liposome-stabilized all
aqueous emulsion droplets as simple artificial mineralizing vesicles (AMVs).
These biomimetic microreactors allow the entry of precursors while retaining a
protein catalyst by equilibrium partitioning between internal and external
polymer-rich phases. Small molecule chelators with intermediate binding affinity
were employed to control Ca(2+) availability during CaCO3 mineralization,
providing protection against liposome aggregation while allowing CaCO3 formation.
Mineral deposition was limited to the AMV interior, due to localized production
of CO3(2-) by compartmentalized urease. Particle formation was uniform across the
entire population of AMVs, with multiple submicrometer amorphous CaCO3 particles
produced in each one. The all-aqueous emulsion-based approach to biomimetic giant
mineral deposition vesicles introduced here should be adaptable for enzyme
catalyzed synthesis of a wide variety of materials, by varying the metal ion,
enzyme, and/or chelator.
PMID- 26422265
TI - Kinetics and Thermodynamics of Reserpine Adsorption onto Strong Acidic Cationic
Exchange Fiber.
AB - The kinetics and thermodynamics of the adsorption process of reserpine adsorbed
onto the strong acidic cationic exchange fiber (SACEF) were studied by batch
adsorption experiments. The adsorption capacity strongly depended on pH values,
and the optimum reserpine adsorption onto the SACEF occurred at pH = 5 of
reserpine solution. With the increase of temperature and initial concentration,
the adsorption capacity increased. The equilibrium was attained within 20 mins.
The adsorption process could be better described by the pseudo-second-order model
and the Freundlich isotherm model. The calculated activation energy Ea was 4.35
kJ/mol. And the thermodynamic parameters were: 4.97=1000 ng/mL). The
prevalence of iron overload in subjects with a history of allogeneic HSCT was
25.9% (95% CI, 9.4%-42.5%) compared with only 3.7% (95% CI, 0%-10.8%) in subjects
treated without HSCT and 0% in subjects treated with autologous HSCT. No
association was found between serum ferritin levels and the presence of cardiac,
liver, or endocrine dysfunction. The prevalence of iron overload in subjects who
received no HSCT or autologous HSCT is low in our study. A higher prevalence was
found in patients receiving allogeneic HSCT, reiterating the importance of
screening these patients for iron overload in accordance with the current
Children's Oncology Group Long Term Follow-Up Guidelines.
PMID- 26422287
TI - Hypothalamic Glioma in a Patient With Sturge-Weber Syndrome.
AB - Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by
vascular malformations involving brain, skin, and occasionally eyes. There is no
recognized tumor predisposition in patients with SWS as there is with some other
phakomatoses. We present a patient with SWS who developed a low-grade glioma
(LGG). We hypothesize that there could be an association between SWS and LGG
formation, noting that GNAQ mutations have been implicated in the underlying
biology of both SWS and a subset of pediatric LGG. It is suggested that SWS may
be a cancer predisposition syndrome.
PMID- 26422288
TI - Pulmonary Functions in Children With Thalassemia Major.
AB - BACKGROUND: Thalassemia major (TM) is a chronic disease requiring regular
transfusions that may result in generalized iron loading, such as in the heart,
the liver, endocrine organs, and the lungs. We aimed to determine pulmonary
function abnormalities in children with TM in our center. PATIENTS AND METHODS:
In this study, pulmonary function tests (PFTs) of 49 patients with TM who
received regular blood transfusion and had no history of chronic respiratory
disease were evaluated. The relationship between PFTs and the age, the body
surface area, pretransfusional hemoglobin, and serum ferritin was evaluated.
RESULTS: Among the beta-TM patients included in this study, 61% were male and 39%
were female, with a mean age of 10.8+/-3 years (range, 5 to 17 y). The patients'
mean level of ferritin was 3873+/-2011 ng/dL (range, 676 to 9476 ng/dL). A
reduced forced vital capacity (FVC) was found in 33 patients (67%). A reduced
forced expiratory volume in 1 second (FEV1) was found in 15 patients (30%). A
forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratio of
>80% was found in all patients. The peak expiratory flow (PEF) was decreased in
23 patients (46.9%). The forced mid-expiratory flow between 25% and 75% of the
exhaled vital capacity (MEF25%-75%) was decreased in 5 patients (10%). FVC and
FEV1 values in patients with a high ferritin level (>2500 ng/dL) were decreased
compared with patients with a low ferritin level (<2500 ng/dL) (P=0.04, 0.03).
FVC, FEV1, and PEF parameters were negatively correlated with the age and the
body surface area. Age was a predictor of FVC (beta=-0.450, P<0.001), FEV1 (beta=
0.419, P<0.001), and PEF (beta=-0.505, P<0.001), and hemoglobin was a predictor
of FEV1/FVC (beta=0.366, P=0.01) and MEF25%-75% (beta=0.323, P=0.003).
CONCLUSIONS: Our results concluded that the respiratory system should be
evaluated by PFTs even in asymptomatic patients with high serum ferritin levels
during the adolescent period annually to prevent the squeal of pulmonary disease
in TM. Patients who have abnormal PFTs should be reevaluated for compliance with
chelation therapy and the transfusion program.
PMID- 26422289
TI - A Practitioner's Guide to Electronic Cigarettes in the Adolescent Population.
AB - We present guidance on electronic nicotine delivery systems (ENDS) for health
care professionals who care for adolescents. ENDS provide users with inhaled
nicotine in an aerosolized mist. Popular forms of ENDS include e-cigarettes and
vape-pens. ENDS range in disposability, customization, and price. Growth of ENDS
usage has been particularly rapid in the adolescent population, surpassing that
of conventional cigarettes in 2014. Despite surging use throughout the United
States, little is known about the health risks posed by ENDS, especially in the
vulnerable adolescent population. These products may potentiate nicotine
addiction in adolescents and have been found to contain potentially harmful
chemicals. The growth in these products may be driven by relaxed purchasing
restrictions for minors, lack of advertising regulations, and youth friendly
flavors. Taken together, ENDS represent a new and growing health risk to the
adolescent population, one that health care professionals should address with
their patients. We suggest a patient centered strategy to incorporate ENDS use
into routine substance counseling.
PMID- 26422290
TI - Avoidant/Restrictive Food Intake Disorder: Illness and Hospital Course in
Patients Hospitalized for Nutritional Insufficiency.
AB - PURPOSE: Avoidant/restrictive food intake disorder (ARFID), a recently defined
Diagnostic and Statistical Manual of Mental Disorders-5 eating disorder
diagnosis, has not been extensively studied in the inpatient population. This
study compares hospitalized ARFID and anorexia nervosa (AN) patients, including
differences in presentation, treatment response, and 1-year outcomes. METHODS: We
conducted a retrospective chart review of ARFID and AN patients hospitalized
between 2008 and 2014 for acute medical stabilization at an academic medical
center. Data, including characteristics on admission, during hospitalization, and
1 year after discharge, were recorded for each patient and compared between ARFID
and AN patients. RESULTS: On presentation, ARFID patients (n = 41) were younger
with fewer traditional eating disorder behaviors and less weight loss,
comorbidity, and bradycardia than AN patients (n = 203). During hospitalization,
although ARFID and AN patients had similar caloric intake, ARFID patients relied
on more enteral nutrition and required longer hospitalizations than AN patients
(8 vs. 5 days; p = .0006). One year after discharge, around half of ARFID and AN
patients met criteria for remission (62% vs. 46%; p = .18), and less than one
quarter required readmission (21% vs. 24%; p = .65). CONCLUSIONS: The findings
from this study reveal several differences in hospitalized eating disorder
patients and emphasize the need for further research on ARFID patients, including
research on markers of illness severity and optimal approaches to refeeding.
Similar remission and readmission rates among ARFID and AN patients highlight
both the success and the continued need for improvement in eating disorder
treatment regardless of diagnosis.
PMID- 26422292
TI - Magnetic resonance imaging of the small bowel in Crohn disease: A systematic
review and meta-analysis.
PMID- 26422291
TI - Somatic p.T771R KDR (VEGFR2) Mutation Arising in a Sporadic Angioma During
Ramucirumab Therapy.
AB - IMPORTANCE: Inhibition of angiogenesis is an effective anticancer strategy
because neoplasms require a rich blood supply. Ramucirumab, approved by the US
Food and Drug Administration in 2014 to treat gastric adenocarcinomas and non
small cell lung carcinomas, targets vascular endothelial growth factor 2
(VEGFR2). We identified a patient prescribed a regimen of irinotecan
hydrochloride, cetuximab, and ramucirumab for metastatic rectal cancer (diagnosed
in November 2013 and treated through early January 2015) who developed a new
onset, expanding vascular lesion on his right leg. Via exome sequencing, we found
that the lesion contained a single somatic mutation in KDR (encodes VEGFR2),
possibly in response to ramucirumab. Vascular tumors are not a known complication
of antiangiogenic therapeutics. OBSERVATIONS: Exome sequencing of the well
demarcated, blanching vascular lesion on the lateral right shin revealed a
somatic p.T771R mutation in KDR, without evidence of other somatic mutations or
loss of heterozygosity. Histological features included lobules of small vessels
within the dermis, resembling a tufted angioma. CONCLUSIONS AND RELEVANCE: A
potential adverse effect of ramucirumab in combination therapy is the development
of sporadic angiomas. The p.T771R mutation was previously implicated in
autophosphorylation of VEGFR2 and reported in angiosarcomas alongside other
driver mutations. Our observations suggest that this mutation confers a
proliferative advantage in the setting of ramucirumab therapy. Patients receiving
ramucirumab should be monitored for the development of new vascular lesions.
PMID- 26422293
TI - Celiac disease and gluten-free oats: A Canadian position based on a literature
review.
PMID- 26422294
TI - Development Trends in Porous Adsorbents for Carbon Capture.
AB - Accumulation of greenhouse gases especially CO2 in the atmosphere leading to
global warming with undesirable climate changes has been a serious global
concern. Major power generation in the world is from coal based power plants.
Carbon capture through pre- and post- combustion technologies with various
technical options like adsorption, absorption, membrane separations, and chemical
looping combustion with and without oxygen uncoupling have received considerable
attention of researchers, environmentalists and the stake holders. Carbon capture
from flue gases can be achieved with micro and meso porous adsorbents. This
review covers carbonaceous (organic and metal organic frameworks) and
noncarbonaceous (inorganic) porous adsorbents for CO2 adsorption at different
process conditions and pore sizes. Focus is also given to noncarbonaceous micro
and meso porous adsorbents in chemical looping combustion involving insitu CO2
capture at high temperature (>400 degrees C). Adsorption mechanisms, material
characteristics, and synthesis methods are discussed. Attention is given to
isosteric heats and characterization techniques. The options to enhance the
techno-economic viability of carbon capture techniques by integrating with CO2
utilization to produce industrially important chemicals like ammonia and urea are
analyzed. From the reader's perspective, for different classes of materials, each
section has been summarized in the form of tables or figures to get a quick
glance of the developments.
PMID- 26422295
TI - The Effect of Tissue Entrapment on Screw Loosening at the Implant/Abutment
Interface of External- and Internal-Connection Implants: An In Vitro Study.
AB - PURPOSE: To compare the removal of torque values of machined implant abutment
connections (internal and external) with and without soft tissue entrapment using
an in vitro model. MATERIALS AND METHODS: Thirty external- and 30 internal
connection implants were embedded in urethane dimethacrylate. Porcine tissue was
prepared and measured to thicknesses of 0.5 and 1.0 mm. Six groups (n = 10) were
studied: External- and internal-connection implants with no tissue (control),
0.5, and 1.0 mm of tissue were entrapped at the implant/abutment interface.
Abutments were inserted to 20 Ncm for all six groups. Insertion torque values
were recorded using a digital torque gauge. All groups were then immersed in 1 M
NaOH for 48 hours to dissolve tissue. Subsequent reverse torque measurements were
recorded. Mean and standard deviation were determined for each group, and one-way
ANOVA and Bonferroni test were used for statistical analysis. RESULTS: All 60
specimens achieved a 20-Ncm insertion torque, despite tissue entrapment. Reverse
torque measurements for external connection displayed a statistically significant
difference (p < 0.05) between all groups with mean reverse torque values for the
control (13.71 +/- 1.4 Ncm), 0.5 mm (7.83 +/- 2.4 Ncm), and 1.0 mm tissue
entrapment (2.29 +/- 1.4 Ncm) groups. Some statistically significant differences
(p < 0.05) were found between internal-connection groups. In all specimens,
tissue did not completely dissolve after 48 hours. CONCLUSIONS: External
connection implants were significantly affected by tissue entrapment; the thicker
the tissue, the lower the reverse torque values noted. Internal-connection
implants were less affected by tissue entrapment.
PMID- 26422296
TI - Highly Improved Efficiency of Deep-Blue Fluorescent Polymer Light-Emitting Device
Based on a Novel Hole Interface Modifier with 1,3,5-Triazine Core.
AB - We present an investigation of deep-blue fluorescent polymer light-emitting
diodes (PLEDs) with a novel functional 1,3,5-triazine core material (HQTZ)
sandwiched between poly(3,4-ethylene dioxythiophene):poly(styrene sulfonic acid)
layer and poly(vinylcarbazole) layer as a hole injection layer (HIL) without
interface intermixing. Ultraviolet photoemission spectroscopy and Kelvin probe
measurements were carried out to determine the change of anode work function
influenced by the HQTZ modifier. The thin HQTZ layer can efficiently maximize the
charge injection from anode to blue emitter and simultaneously enhance the hole
mobility of HILs. The deep-blue device performance is remarkably improved with
the maximum luminous efficiency of 4.50 cd/A enhanced by 80% and the maximum
quantum efficiency of 4.93%, which is 1.8-fold higher than that of the
conventional device without HQTZ layer, including a lower turn-on voltage of 3.7
V and comparable Commission Internationale de L'Eclairage coordinates of (0.16,
0.09). It is the highest efficiency ever reported to date for solution-processed
deep-blue PLEDs based on the device structure of ITO/HILs/poly(9,9-dialkoxyphenyl
2,7-silafluorene)/CsF/AL. The results indicate that HQTZ based on 1,3,5-triazine
core can be a promising candidate of interfacial materials for deep-blue
fluorescent PLEDs.
PMID- 26422297
TI - Postsynthetic conjugation of RNA to carboxylate and dicarboxylate molecules.
AB - Carboxylates and dicarboxylates are important phosphate mimics. Herein, we
present a simple synthetic route for the preparation of RNA
carboxylate/dicarboxylate conjugates, starting from suitably protected NH2- and
COOH-containing molecules that are coupled to the RNA on the solid support. The
key point in our method was the use of trimethylsilylethanol (TMSE-OH) protecting
group, which is removed simultaneously with the silyl protecting group on the 2'
OH of the RNA ribose (e.g. t-Butyldimethylsilyl) during the final RNA
cleavage/deprotection steps. The usefulness of this method was demonstrated by
preparing different RNA-phosphate mimics oligos.
PMID- 26422299
TI - Paroxysmal nocturnal hemoglobinuria and hematopoietic stem cell transplantation:
Better results in 2015?
PMID- 26422298
TI - A quantitative benefit-risk assessment approach to improve decision making in
drug development: Application of a multicriteria decision analysis model in the
development of combination therapy for overactive bladder.
AB - A multicriteria decision analysis (MCDA) approach was developed and used to
estimate the benefit-risk of solifenacin and mirabegron and their combination in
the treatment of overactive bladder (OAB). The objectives were 1) to develop an
MCDA tool to compare drug effects in OAB quantitatively, 2) to establish
transparency in the evaluation of the benefit-risk profile of various dose
combinations, and 3) to quantify the added value of combination use compared to
monotherapies. The MCDA model was developed using efficacy, safety, and
tolerability attributes and the results of a phase II factorial design
combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron
25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and
supported combination therapy development of solifenacin and mirabegron for phase
III clinical development at these dose regimens. This case study underlines the
benefit of using a quantitative approach in clinical drug development programs.
PMID- 26422300
TI - Usefulness of scheduled follow-up CT in discharged patients with acute
pancreatitis.
AB - BACKGROUND AND AIM: Follow-up computed tomography (CT) in patients with acute
pancreatitis has been advocated but rarely studied. The aim of this study was to
determine whether follow-up CT for acute pancreatitis might be helpful in
establishing the prognosis or complications, and in determining a selected
subgroup of patients for whom computed tomography could be beneficial. METHODS:
Between January 2010 and December 2012, patients with acute pancreatitis who
underwent follow-up CT in the outpatient department between one and three months
after discharge were retrospectively enrolled. Events discovered on follow-up CT
were defined as newly developed or increased pancreatic collection such as
pseudocyst or walled off necrosis, and diagnosis of pancreatic cancer. RESULTS:
Ultimately, 106 asymptomatic patients were enrolled (mean age 50.24 +/- 16, 74.5%
male, 31.1% moderately severe and severe acute pancreatitis). The median duration
of follow-up CT was 69 (31-90) days. On follow-up CT, 23 patients showed events
(2 pancreatic cancer, 21 increasing or developed pancreatic collections). In
multivariate analysis, the predictive factors for events on follow-up CT were
CTSI >=3 (OR 4.46, CI 1.08-18.43, p = 0.039) and BISAP >= 2 (OR 4.83, CI 1.08
21.55, p = 0.039). CONCLUSIONS: Follow-up CT within three months after discharge
may be helpful for acute pancreatitis patients with CTSI >= 3 points or BISAP
score >= 2 points.
PMID- 26422302
TI - Direct electrokinetic injection of inorganic cations from whole fruits and
vegetables for capillary electrophoresis analysis.
AB - A novel approach for the direct injection from plant tissues without any sample
pre-treatment has been developed by simply placing a small piece of the tissue
into a capillary electrophoresis vial followed by application of a voltage for
electrokinetic injection. Separations of sodium, potassium, calcium and magnesium
were achieved using a BGE comprising 10mM imidazole and 2.5mM 18-crown-6-ether at
pH 4.5. The addition of 2% (m/v) hydroxypropylmethyl cellulose to the separation
buffer allowed for precise and accurate electrokinetic injection of ions from the
plant material by halting the movement of tissue fluid into the capillary. This
method provides both qualitative and quantitative data of inorganic cations, with
quantitation in zucchini, mushroom and apple samples in agreement with Sector
Field Inductively Coupled Plasma Mass Spectrometric analysis (r(2)=0.98, n=9).
This method provides a new way for rapid, quantitative analysis by eliminating
sample preparation procedures, and has great potential for a range of
applications in plant science and food chemistry.
PMID- 26422303
TI - Use of MiniColumns for linear isotherm parameter estimation and prediction of
benchtop column performance.
AB - In this paper, a comparison between experimental chromatography data and column
simulations is carried out to determine the efficacy of using miniaturized
chromatography columns (MiniColumns) for both column modeling parameter
estimation and process development. Normalization of the data with respect to
column volumes along with appropriate translations to account for system
differences is shown to result in comparability of the experimental data for the
MiniColumn and benchtop systems. A parameter estimation protocol is then employed
to determine the linear steric mass-action (SMA) isotherm and lumped mass
transport parameters for two cation exchange resins. The models are then
validated and simulations using different parameter sets from the MiniColumn and
benchtop systems are shown to result in similar predicted chromatography profiles
and calculated retention volumes. The parameters generated from the MiniColumn
system are demonstrated to be well suited for predicting experimental data from
the benchtop system. These simulation results, the ability to operate MiniColumns
in parallel, and the significantly lower material requirements per experiment
support an industry trend toward increased usage of miniaturized chromatography
columns as a scale-down model for process development.
PMID- 26422305
TI - Feasibility of correlating separation of ternary mixtures of neutral analytes via
thin layer chromatography with supercritical fluid chromatography in support of
green flash separations.
AB - Method development for normal phase flash liquid chromatography traditionally
employs preliminary screening using thin layer chromatography (TLC) with
conventional solvents on bare silica. Extension to green flash chromatography via
correlation of TLC migration results, with conventional polar/nonpolar liquid
mixtures, and packed column supercritical fluid chromatography (SFC) retention
times, via gradient elution on bare silica with a suite of carbon dioxide mobile
phase modifiers, is reported. Feasibility of TLC/SFC correlation is individually
described for eight ternary mixtures for a total of 24 neutral analytes. The
experimental criteria for TLC/SFC correlation was assumed to be as follows:
SFC/UV/MS retention (tR) increases among each of the three resolved mixture
components; while, TLC migration (Rf) decreases among the same resolved mixture
components. Successful correlation of TLC to SFC was observed for most of the
polar organic solvents tested, with the best results observed via SFC on bare
silica with methanol as the CO2 modifier and TLC on bare silica with a
methanol/dichloromethane mixture.
PMID- 26422304
TI - Comparison of sodium dodecyl sulfate depletion techniques for proteome analysis
by mass spectrometry.
AB - In proteomics, sodium dodecyl sulfate (SDS) is favored for protein solubilization
and mass-based separation (e.g. GELFrEE or SDS PAGE). Numerous SDS depletion
techniques are available to purify proteins ahead of mass spectrometry. The
effectiveness of the purification has a controlling influence on the success of
the analysis. Here we quantitatively assess eight approaches to SDS depletion: in
gel digestion; protein precipitation in acetone or with TCA; detergent
precipitation with KCl; strong cation exchange; protein level and peptide level
purification with Pierce detergent removal cartridges; and FASP II. Considering
protein purity, FASP II showed the highest degree of SDS removal, matching that
of in-gel digestion (over 99.99% depleted). Other methods (acetone, strong cation
exchange, Pierce cartridges) also deplete SDS to levels amenable to LC-MS (>99%).
Accounting for protein recovery, FASP II revealed significant sample loss (<40%
yield); other approaches show even greater protein loss. We further assessed
acetone precipitation, having the highest protein recovery relative to FASP II,
to process GELFrEE fractionated Escherichia coli ahead of bottom-up mass
spectrometry. Acetone precipitation yielded a 17% average increase in identified
proteins, and 40% increase in peptides, indicating this approach as a favored
strategy for SDS depletion in a proteomics workflow.
PMID- 26422306
TI - Mild and cost-effective green fluorescent protein purification employing small
synthetic ligands.
AB - The green fluorescent protein (GFP) is a useful indicator in a broad range of
applications including cell biology, gene expression and biosensing. However, its
full potential is hampered by the lack of a selective, mild and low-cost
purification scheme. In order to address this demand, a novel adsorbent was
developed as a generic platform for the purification of GFP or GFP fusion
proteins, giving GFP a dual function as reporter and purification tag. After
screening a solid-phase combinatorial library of small synthetic ligands based on
the Ugi-reaction, the lead ligand (A4C7) selectively recovered GFP with 94% yield
and 94% purity under mild conditions and directly from Escherichia coli extracts.
Adsorbents containing the ligand A4C7 maintained the selectivity to recover other
proteins fused to GFP. The performance of A4C7 adsorbents was compared with two
commercially available methods (immunoprecipitation and hydrophobic interaction
chromatography), confirming the new adsorbent as a low-cost viable alternative
for GFP purification.
PMID- 26422307
TI - Online post-column solvent assisted and direct solvent-assisted electrospray
ionization for chiral analysis of propranolol enantiomers in plasma samples.
AB - An Online post-column solvent-assisted ionization (OPSAI) method was developed
for enhancing the ionization of the beta-blocker propranolol utilizing normal
phase LC-MS/MS. Solvent-assisted electrospray ionization (SAESI) was studied by
the introduction of the assistant solvents A: 0.5% Formic acid in Isopropanolol,
B: 0.5% Formic acid in Isopropanolol-Water (1:1), and C: 0.5% Formic acid in
water into the electrospray ionization chamber using a spray needle. Analyte
molecules can be directly ionized by the aid of the assistant solvent spray. Both
methods were applied to the chiral separation of propranolol enantiomers using
normal phase analysis on cellulose-based chiral column. Interestingly, both
methods are easy to handle and offer a wide range of assistant solvents that can
be used in order to gain the optimum ionization of the analyte molecules. The
both methods considerably improved the analyte signal and the peak area greatly
increased. The propranolol average signal-to-noise (S/N) ratio was enhanced from
26+/-1 and 42+/-1 to 2341+/-61 and 1725+/-29 for R-propranolol and S-propranolol,
respectively, when the post-column solvent method (OPSAI) was used with
isopropanol-assistant solvent (A). While in case of solvent-assisted electrospray
ionization method (SAESI) signal was enhanced from 26+/-1 and 42+/-1 to 2223+/-72
and 2155+/-58 for R-propranolol and S-propranolol, respectively, with water as an
assistant solvent. The limit of detection was 10ng/mL and the method was linear
in the range 50-2000ng/mL. The NPLC-MS method was applied for the determination
of propranolol enantiomers in human plasma after microextraction by packed C18
sorbent.
PMID- 26422308
TI - Electronic cigarette solutions and resultant aerosol profiles.
AB - Electronic cigarettes (e-cigarettes) are growing in popularity exponentially.
Despite their ever-growing acceptance, their aerosol has not been fully
characterized. The current study focused on evaluating e-cigarette solutions and
their resultant aerosol for potential differences. A simple sampling device was
developed to draw e-cigarette aerosol into a multi-sorbent thermal desorption
(TD) tube, which was then thermally extracted and analyzed via a gas
chromatography (GC) mass spectrometry (GC-MS) method. This novel application
provided detectable levels of over one hundred fifteen volatile organic compounds
(VOCs) and semivolatile organic compounds (SVOCs) from a single 40mL puff. The
aerosol profiles from four commercially available e-cigarettes were compared to
their respective solution profiles with the same GC-MS method. Solution profiles
produced upwards of sixty four unidentified and identified (some only
tentatively) constituents and aerosol profiles produced upwards of eighty two
compounds. Results demonstrated distinct analyte profiles between liquid and
aerosol samples. Most notably, formaldehyde, acetaldehyde, acrolein, and
siloxanes were found in the aerosol profiles; however, these compounds were never
present in the solutions. These results implicate the aerosolization process in
the formation of compounds not found in solutions; have potential implications
for human health; and stress the need for an emphasis on electronic cigarette
aerosol testing.
PMID- 26422309
TI - A resolution approach of racemic phenylalanine with aqueous two-phase systems of
chiral tropine ionic liquids.
AB - Aqueous two-phase systems (ATPS) based on tropine type chiral ionic liquids and
inorganic salt solution were designed and prepared for the enantiomeric
separation of racemic phenylalanine. The phase behavior of IL-based ATPS was
comprehensive investigated, and phase equilibrium data were correlated by Merchuk
equation. Various factors were also systematically investigated for their
influence on separation efficiency. Under the appropriate conditions (0.13g/g
[C8Tropine]pro, 35mg/g Cu(Ac)2, 20mg/g d,l-phenylalanine, 0.51g/g H2O and 0.30g/g
K2HPO4), the enantiomeric excess value of phenylalanine in solid phase (mainly
containing l-enantiomer) was 65%. Finally, the interaction mechanism was studied
via 1D and 2D NMR. The results indicate that d-enantiomer of phenylalanine
interacts more strongly with chiral ILs and Cu(2+) based on the chiral ion-pairs
space coordination mechanism, which makes it tend to remain in the top IL-rich
phase. By contrast, l-enantiomer is transferred into the solid phase. Above
chiral ionic liquids aqueous two-phase systems have demonstrated obvious
resolution to racemic phenylalanine and could be promising alterative resolution
approach for racemic amino acids in aqueous circumstance.
PMID- 26422310
TI - [Which Articles are Favored by Readers of the PPmP?].
PMID- 26422311
TI - [Work Life Participation of Mentally Ill Individuals--Implications for Research
and Best Practice].
AB - Participation in working life improves the health outcome of mentally ill
individuals. The paper reviews the current situation of mentally ill individuals
and barriers to enter the open labour market. Barriers are discussed and the
contribution of mental health professionals is outlined. Implications for
research and best practice are considered.
PMID- 26422312
TI - [Psychotherapy in Palliative Care].
PMID- 26422313
TI - [In Process Citation].
PMID- 26422314
TI - Racial matching and adolescent self-disclosure of substance use and mental health
symptoms.
AB - Obtaining accurate assessment data from adolescents in treatment aids clinical
decision making and facilitates more accurate outcome evaluations. However,
findings could be biased due to underreported substance use and mental health
symptoms. This article compares self-reports of youth in non-White matched client
assessor dyads and those in nonmatched dyads. There were no differences on self
reported substance use, but matched youth reported significantly fewer attention
deficit/hyperactivity disorder symptoms versus the comparison group. One possible
reason for these findings is the effect of in-group stereotype threat. Future
studies should examine the potential effect that in-group stereotyping and
perceived racism have on the therapeutic relationship.
PMID- 26422315
TI - Isolation and identification of a novel peptide from zein with antioxidant and
antihypertensive activities.
AB - The aim of this study is to isolate and identify a novel corn peptide (CP) from
zein with antioxidant and antihypertensive activities based on bioactive-guided
isolation procedures. Zein was hydrolyzed by using double enzymes immobilized
with calcium alginate-chitosan beads and then fractionated and purified. The
antioxidant and antihypertensive activities of the CP fractions were screened by
in vitro and in vivo assays. The in vivo animal studies using spontaneously
hypertensive rats (SHRs) confirmed the antihypertensive effects of the CP, and
its angiotensin I-converting enzyme (ACE) inhibitory activity was retained after
thermal treatment and simulated gastrointestinal digestion. The primary structure
of CP-2-1 was identified by RP-HPLC-MS/MS and the amino acid sequence was
determined as M-I/L-P-P with the molecular weight of 452.3 Da. CP-2-1 showed
effective antioxidant and ACE inhibitory activities (IC50 values of 220 MUg mL(
1) and 70.32 MUg mL(-1), respectively) and it might be a potential candidate for
antioxidant functional food or pharmaceuticals for hypertension.
PMID- 26422316
TI - Irisin: A true, circulating hormone.
PMID- 26422317
TI - Cyclic Deformation in Metallic Glasses.
AB - Despite the utmost importance and decades of experimental studies on fatigue in
metallic glasses (MGs), there has been so far little or no atomic-level
understanding of the mechanisms involved. Here we perform molecular dynamics
simulations of tension-compression fatigue in Cu50Zr50 MGs under strain
controlled cyclic loading. It is shown that the shear band (SB) initiation under
cyclic loading is distinctly different from that under monotonic loading. Under
cyclic loading, SB initiation takes place when aggregates of shear transformation
zones (STZs) accumulating at the MG surface reach a critical size comparable to
the SB width, and the accumulation of STZs follows a power law with rate
depending on the applied strain. It is further shown that almost the entire
fatigue life of nanoscale MGs under low cycle fatigue is spent in the SB
initiation stage, similar to that of crystalline materials. Furthermore, a
qualitative investigation of the effect of cycling frequency on the fatigue
behavior of MGs suggests that higher cycling frequency leads to more cycles to
failure. The present study sheds light on the fundamental fatigue mechanisms of
MGs that could be useful in developing strategies for their engineering
applications.
PMID- 26422318
TI - Forsythoneosides A-D, Neuroprotective Phenethanoid and Flavone Glycoside
Heterodimers from the Fruits of Forsythia suspensa.
AB - Forsythoneosides A-D (1-4), four unusual adducts of a flavonoid unit fused to a
phenylethanoid glycoside through a pyran ring or carbon-carbon bond, and four new
phenylethanoid glycosides (5-8) were isolated from the fruits of Forsythia
suspensa, together with nine known compounds. The structures of 1-8, including
their absolute configurations, were elucidated by spectroscopic data as well as
experimental and calculated electronic circular dichroism analysis. Compounds 2
and 4 inhibited PC12 cell damage induced by rotenone, and increased cell
viability from 53.9 +/- 7.1% to 70.1 +/- 4.0% and 67.9 +/- 5.2% at 0.1 MUM,
respectively.
PMID- 26422319
TI - Association of P-Wave Dispersion with Overall and Cardiovascular Mortality in
Hemodialysis Patients.
AB - BACKGROUND/AIMS: The P-wave parameters that are measured using a 12-lead
electrocardiogram are commonly used as noninvasive tools for assessing left
atrial enlargement. This study was designed to assess whether P-wave dispersion
is associated with overall and cardiovascular mortality in hemodialysis patients.
METHODS: This study enrolled 209 hemodialysis patients. We measured the P-wave
dispersion corrected by heart rate, that is, the corrected P-wave dispersion
(PWdisperC), and assessed its correlation with overall and cardiovascular
mortalities. RESULTS: The mean PWdisperC of all the patients was 93.3 +/- 21.1
ms. During the follow-up period (mean 5.4 years), 58 deaths and 37 cardiovascular
deaths were recorded. The adjusted value of PWdisperC was also associated with
overall (hazards ratio (HR) 1.018, 95% CI 1.004-1.033, p = 0.014) and
cardiovascular (HR 1.032, 95% CI 1.012-1.053, p = 0.002) mortalities.
Multivariate Cox regression analysis identified tertile 3 of PWdisperC (vs.
tertile 1) to be associated with overall (HR 2.472, 95% CI 1.181-5.174, p =
0.016) and cardiovascular (HR 3.896, 95% CI 1.463-10.376, p = 0.007) mortalities,
after adjustment for demographic, clinical and biochemical parameters. Adding
PWdisperC to a model of clinical features could significantly improve the
predictive value for overall (p = 0.044) and cardiovascular (p = 0.002)
mortalities. CONCLUSIONS: We concluded that PWdisperC was positively associated
with overall and cardiovascular mortalities in hemodialysis patients and could
provide additional prognostic values. Screening hemodialysis patients by using
PWdisperC may facilitate identifying a group of patients with poor prognosis.
PMID- 26422320
TI - [Clinical problems in medical mycology: Problem number 49].
AB - The case of a 59-year-old female born in Buenos Aires (Argentina) is presented.
She had been diagnosed with HIV in 2007 and received highly active antiretroviral
therapy until 2011; she also suffered from diabetes type 2. She had received
empirical treatment (pyrimethamine-clindamycin) for cerebral toxoplasmosis.
Fifteen days later she suffered a drug-induced skin disorder and was treated in
the Dermatology Service of the Hospital Muniz with corticosteroids. After five
weeks she was readmitted to the Infectious Disease Unit due to asthenia, weight
loss, left hip pain and weakness in all four limbs. Septic arthritis and aseptic
hip necrosis were ruled out. Blood cultures were positive for Staphylococcus
aureus and Escherichia coli. The patient received intravenous antibiotics, but
before being discharged Acinetobacter baumannii was isolated from blood, catheter
and urine cultures, and a new series of antibiotics were prescribed. On the 3rd
day she presented encephalic facies, changes of behaviour and disorientation,
without nuchal rigidity, Kernig and Brudzinski signs or focal signs. An X-ray
computed tomography did not show parenchymal lesions. A yeast identified as
Candida albicans was isolated in a cerebrospinal fluid culture. The same yeast
was recovered in a new cerebrospinal fluid sample. The isolate was susceptible to
amphotericin B and susceptible dose dependent to fluconazole. The patient was
treated with amphotericin B (0.7mg/kg plus 800mg fluconazole daily). Three weeks
later, new cerebrospinal fluid cultures were negative. Unfortunately, the patient
died soon afterwards.
PMID- 26422321
TI - Antifungal stewardship in a tertiary hospital.
AB - BACKGROUND: The inappropriate use of antifungals is an important health problem
related to increasing adverse effects, unnecessary cost and promotion of
resistant and emerging fungal infections. Despite its relevance, many health
institutions assign few resources to improve prescribing practices. AIMS: To
evaluate the efficiency of an antifungal stewardship programme (ASP) centered on
restricted antifungal agents. METHODS: The main activity during the eight-month
study was to perform a programmed review of restricted antifungals (lipid
formulations of amphotericin B, echinocandins and voriconazole) prescribed in
hospitalized patients. In the case of amendable antifungal treatment, a
recommendation was included in the electronic medical record. RESULTS: A total of
280 antifungal prescriptions for 262 patients were revised during the study
period. The indications were prophylactic in 85 cases (30.4%), pre-emptive in 10
cases (3.5%), empiric in 122 cases (43.6%), and directed in 63 cases (22.5%). A
total of 70 prescriptions (25%) in 61 patients were considered to be amendable.
In most of these cases, treatment could have been reduced considering the
patient's clinical improvement and microbiological results. The most common
advice was antifungals change (70%), antifungal withdrawal (21%), removal of one
antifungal drug in cases of combined therapy (7%), and switching to oral route
(1%). Proposed recommendations were addressed in 28 cases (40%). There was no
significant difference in adherence with respect to the type of recommendation
(p=0.554). There was a 42% lower use of antifungals during the period of the
study compared to that observed during a similar previous period. Mortality among
patients who were treated according to the recommendations of the ASP was 17% and
in whom treatment was not modified it was 30% (p=0.393). CONCLUSIONS: ASPs
centered on hospitalized patients may be an efficient strategy to ameliorate
antifungal use in hospitals.
PMID- 26422322
TI - Cutaneous blastomycosis. An imported case with good response to itraconazole.
AB - BACKGROUND: Blastomycosis is a subacute or chronic deep mycosis caused by a
dimorphic fungus called Blastomyces dermatitidis, which generally produces a
pulmonary form of the disease and, to a lesser extent, extra-pulmonary forms such
as cutaneous, osteoarticular and genitourinary, among others. Cutaneous
blastomycosis is the second clinical presentation in frequency. It is considered
as primary when it begins by inoculation of the fungus due to traumas, and
secondary when the lung fails to contain the infection. CASE-REPORT: We present
the case of a 57 year-old male who had a 5 year-history of an irregularly shaped
verrucous infiltrative plaque related to and insect bite and posterior trauma due
to the manipulation of the lesion. B. dermatitidis was identified using direct
examination, stains, isolation in culture media, histopathology, and molecular
studies. An antifungal susceptibility test was performed using method M38-A2
(CLSI). Clinical and mycological cure was achieved with itraconazole.
CONCLUSIONS: This cutaneous blastomycosis case acquired in the United States
(Indianapolis) is rather interesting and looks quite similar to other mycoses
such as coccidioidomycosis or sporotrichosis. The presented case shows one of the
multiple issues concerning migration between neighboring countries.
PMID- 26422323
TI - Vacuolar proteases from Candida glabrata: Acid aspartic protease PrA, neutral
serine protease PrB and serine carboxypeptidase CpY. The nitrogen source
influences their level of expression.
AB - BACKGROUND: The Saccharomyces cerevisiae vacuole is actively involved in the
mechanism of autophagy and is important in homeostasis, degradation, turnover,
detoxification and protection under stressful conditions. In contrast, vacuolar
proteases have not been fully studied in phylogenetically related Candida
glabrata. AIMS: The present paper is the first report on proteolytic activity in
the C. glabrata vacuole. METHODS: Biochemical studies in C. glabrata have
highlighted the presence of different kinds of intracellular proteolytic
activity: acid aspartyl proteinase (PrA) acts on substrates such as albumin and
denatured acid hemoglobin, neutral serine protease (PrB) on collagen-type hide
powder azure, and serine carboxypeptidase (CpY) on N-benzoyl-tyr-pNA. RESULTS:
Our results showed a subcellular fraction with highly specific enzymatic activity
for these three proteases, which allowed to confirm its vacuolar location.
Expression analyses were performed in the genes CgPEP4 (CgAPR1), CgPRB1 and
CgCPY1 (CgPRC), coding for vacuolar aspartic protease A, neutral protease B and
carboxypeptidase Y, respectively. The results show a differential regulation of
protease expression depending on the nitrogen source. CONCLUSIONS: The proteases
encoded by genes CgPEP4, CgPRB1 and CgCPY1 from C. glabrata could participate in
the process of autophagy and survival of this opportunistic pathogen.
PMID- 26422324
TI - [Effects of pesticides and plant bio-stimulants on the germination of
chlamydospores and in vitro development of the nematophagous fungus Pochonia
chlamydosporia].
AB - BACKGROUND: The effects of pesticides and plant bio-stimulants used in protected
vegetable production systems on the fungus Pochonia chlamydosporia are unknown.
AIMS: The effectiveness of P. chlamydosporia against Meloidogyne spp. could be
affected by products used in protected vegetable production systems. Two in vitro
assays were carried out to evaluate any potential effect that pesticides and bio
stimulants often used in these systems could have on the fungus. METHODS: The
effect on chlamydospore germination was evaluated in a first assay, and mycelia
growth and sporulation in a second. With these results, the compatibility of each
product with the fungus was determined. RESULTS: Chlamydospores germination was
over 50% with the control, FitoMas E, Biobras-16 and Amidor. Lower results were
observed with other products, with some of them even inhibiting germination
completely. Fungal growth was potentiated by Biobras-16 to 106.23%, promoted up
to 50-100% by the control, FitoMas E and Cuproflow, and was below 50% with the
rest of the products.Cipermetrina, Benomilo, Zineb, Mitigan, Karate, FitoMas E
and Amidor promoted fungal sporulation, which was below 50% with Cuproflow and
completely inhibited by the other products. Fifty-four percent of the products
evaluated were compatible with P. chlamydosporia, while 8% were toxic and 38%,
very toxic. CONCLUSIONS: Cipermetrina, Karate, Amidor, Benomilo, Zineb, Mitigan
and FitoMas E were compatible with P. chlamydosporia. If it is necessary to use
any of the other products for integrated pest management in protected vegetable
production systems, it is recommended to avoid direct contact with P.
chlamydosporia.
PMID- 26422325
TI - [Clinical problems in medical mycology: Problem number 48].
AB - We present the case of a 42-year-old man, HIV-positive, with low CD4(+) T cell
count (31 cells/MUl), who was admitted to Hospital de Infecciosas F. J. Muniz in
Buenos Aires (Argentina) due to a severe lower back pain. He had a history of
several highly active antiretroviral therapy treatments and he also had diabetes
and chronic B and C viral hepatitis. A spinal cord CT scan showed two lytic bone
lesions in L2 and L3. A bone biopsy was carried out and its microbiological study
allowed the isolation of a methicillin-resistant Staphylococcus aureus.
Intravenous vancomycin was prescribed, together with a corset and physical rest.
A few days later the patient presented with acute dermatitis with papules,
vesicles, scales and erythema, which spread over the whole lumbar region. The
mycological study of the scales led to the isolation in culture of Candida
albicans and Candida parapsilosis. With the diagnosis of decubitus candidiasis he
was initially treated with a topical ointment containing 3% salicylic acid and 6%
benzoic acid, but only slow, partial improvement was observed. The treatment was
changed to oral fluconazole at a daily dose of 200mg. With the latter the patient
showed a rapid, complete clinical response.
PMID- 26422326
TI - Intravenous Morphine Sulfate versus Intravenous Tramadol for Acute Pain in the
Afghan National Security Forces.
PMID- 26422327
TI - Family Presence During Resuscitation Benefits-Risks Scale (FPDR-BRS): Instrument
Development and Psychometric Validation.
AB - Family presence during resuscitation (FPDR) is a growing health care practice;
nevertheless, countless controversies surround this medical principle. Several
studies have investigated the perceptions of health care professionals toward
FPDR, yet psychometrically sound instruments assessing family members'
perceptions of FPDR are scarce. Hence we aimed to develop and psychometrically
validate the Family Presence During Resuscitation Benefits-Risks Scale (FPDR
BRS). METHODS: Using a methodological design, an initial 27-item questionnaire
was developed after extensive literature and theoretical review. Psychometric
validation assessed content validity through a 2-step process involving expert
nurses and doctors, basic item analysis, internal consistency using Cronbach's
alpha, and construct validity via exploratory factor analysis. After acquiring
Ethics Review Board approval, the FPDR-BRS was tested on 130 randomly selected
eligible family members from a tertiary government hospital in the Philippines.
RESULTS: The initial 27-item questionnaire was reduced to 23 items after content
validation, yielding an item content validity index and scale content validity
index/Ave rage of 1.00. Basic item analysis revealed acceptable inter-item and
item-scale correlations. Exploratory factor analysis extracted 4 factors, namely,
personnel risks, personal risks, insight-building benefits, and connection
forming benefits. Cronbach's alpha for the entire scale was 0.90, with high
subscale reliability coefficients. DISCUSSION: The 23-item FPDR-BRS exhibited
satisfactory psychometric properties and may be used to quantitatively measure a
family member's perception towards witnessing the resuscitation of his or her
significant other. Further comprehensive psychometric evaluations are warranted
to ensure robust cross-cultural comparisons.
PMID- 26422328
TI - A cost and time analysis of laryngology procedures in the endoscopy suite versus
the operating room.
AB - OBJECTIVES/HYPOTHESIS: To assess the costs, charges, reimbursement, and
efficiency of performing awake laryngology procedures in an endoscopy suite (ES)
compared with like procedures performed in the operating room (OR). STUDY DESIGN:
Retrospective review of billing records. METHODS: Cost, charges, and
reimbursements for the hospital, surgeon, and anesthesiologist were compared
between ES injection laryngoplasty and laser excision procedures and matched case
controls in the OR. Time spent in 1) the preoperative unit, 2) the operating or
endoscopy suite, and 3) recovery unit were compared between OR and ES procedures.
RESULTS: Hospital expenses were significantly less for ES procedures when
compared to OR procedures. Reimbursement was similar for ES and OR injection
laryngoplasty, though greater for OR laser excisions. Net balance (reimbursement
expenses) was greater for ES procedures. A predictive model of payer costs over a
3-year period showed similar costs for ES and OR laser procedures and reduced
costs for ES compared to OR injection laryngoplasty. Times spent preoperatively
and the procedure were significantly less for ES procedures. CONCLUSIONS: For
individual laryngology procedures, the ES reduces time and costs compared to the
OR, increasing otolaryngologist and hospital efficiency. This reveals cost and
time savings of ES injection laryngoplasty, which occurs at a similar frequency
as OR injection laryngoplasty. Given the increased frequency for ES laser
procedures, total costs are similar for ES and OR laser excision of papilloma,
which usually require repeated procedures. When regulated office space is
unavailable, endoscopy rooms represent an alternative setting for unsedated
laryngology procedures. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1385-1389, 2016.
PMID- 26422329
TI - Rate and duration of hospitalization for deep vein thrombosis and pulmonary
embolism in real-world clinical practice.
AB - BACKGROUND: Current guidelines recommend initial treatment with anticoagulants at
home in patients with acute deep vein thrombosis (DVT) and in patients with low
risk pulmonary embolism (PE) with adequate home circumstances. However, most of
the patients with acute venous thromboembolism (VTE) are currently hospitalized
regardless of their risk of short-term complications. AIM OF THE STUDY: To assess
the proportion of outpatients with acute VTE initially treated in hospitals, to
assess the mean duration of hospitalization, and to identify predictors for in
hospital or home treatment. METHODS: Data of Italian patients enrolled in the
RIETE registry from January 2006 to December 2013 were included. RESULTS:
Altogether 766 PE and 1,452 isolated DVT were included. Among PE patients, mean
PESI score was 84 points (SD 35), and 56% of patients had a low-risk PESI score
(<85). In all, 53.7% of DVT and 17.0% of PE were entirely treated at home, and
38.2% of DVT patients and 19.9% of PE patients were hospitalized for <=5 days. On
multivariate analysis, low PESI score was not independently associated with the
hospitalization of PE patients. CONCLUSIONS: One in every two patients with DVT
and five in every six with PE are still hospitalized.
PMID- 26422330
TI - Validation of the Brazilian version of the childhood asthma control test (c-ACT).
AB - BACKGROUND: Children's perception of their symptoms has proved reliable and
relevant to disease management and should be considered when assessing their
asthma control. The aim of the study is to validate the Brazilian Portuguese
version of the Childhood Asthma Control Test (c-ACT) in children aged 4-11 years.
METHODS: This is a cross-sectional study in children diagnosed with asthma
undergoing treatment in a pediatric pulmonology outpatient clinic in Porto
Alegre, Brazil. The translation and linguistic adaptation of the instrument were
performed in accordance with international recommendations for questionnaire
validation. RESULTS: A total of 105 participants were included, aged 4-11 years.
VALIDITY: all correlations between the total score and items on the questionnaire
were significant and obtained values of r >= 0.3, and c-ACT means showed
statistically significant differences between the GINA categories (P < 0.01). The
controlled asthma group showed significantly higher c-ACT scores than those of
uncontrolled asthma group (controlled 22.0 +/- 2.9 vs. uncontrolled 16.3 +/- 5.3
P < 0.01); and partially controlled asthma group showed significantly higher c
ACT scores than those of uncontrolled asthma group (partially controlled 20.0 +/-
4.0 vs. uncontrolled 16.3 +/- 5.3 P = 0.03). Correlations between the c-ACT total
score and spirometry and nitric oxide were poor (r = 0.020; P = 0.866 and r =
0.035; P = 0.753, respectively). Reliability: the alpha-C coefficient for the c
ACT total score was 0.677 (95%CI 0.573-0763). Sensitivity to change had an effect
size of 0.8 and an intraclass correlation coefficient of 0.598. No floor or
ceiling effects were observed. CONCLUSION: The Brazilian version of the Childhood
Asthma Control Test proved to be valid and reliable in children aged 4-11 years.
PMID- 26422332
TI - The pathway of collagen secretion.
AB - COPII vesicles mediate export of secretory cargo from the endoplasmic reticulum
(ER). However, a standard COPII vesicle with a diameter of 60-90 nm is too small
to export collagens that are composed of rigid triple helices of up to 400 nm in
length. How do cells pack and secrete such bulky molecules? This issue is
fundamentally important, as collagens constitute approximately 25% of our dry
body weight and are essential for almost all cell-cell interactions. Recently, a
potential mechanism for the biogenesis of mega-transport carriers was identified,
involving packing collagens and increasing the size of COPII coats. Packing is
mediated by TANGO1, which binds procollagen VII in the lumen and interacts with
the COPII proteins Sec23/Sec24 on the cytoplasmic side of the ER. Cullin3, an E3
ligase, and its specific adaptor protein, KLHL12, ubiquitinate Sec31, which could
increase the size of COPII coats. Recruitment of these proteins and their
specific interactors into COPII-mediated vesicle biogenesis may be all that is
needed for the export of bulky collagens from the ER. Nonetheless, we present an
alternative pathway in which TANGO1 and COPII cooperate to export collagens
without generating a mega-transport carrier.
PMID- 26422331
TI - The marriage of surgical simulation and telementoring for damage-control surgical
training of operational first responders: A pilot study.
AB - BACKGROUND: Hemorrhage is the leading cause of preventable posttraumatic death.
Many such deaths may be potentially salvageable with remote damage-control
surgical interventions. As recent innovations in information technology enable
remote specialist support to point-of-care providers, advanced interventions,
such as remote damage-control surgery, may be possible in remote settings.
METHODS: An anatomically realistic perfused surgical training mannequin with
intrinsic fluid loss measurements (the "Cut Suit") was used to study perihepatic
packing with massive liver hemorrhage. The primary outcome was loss of simulated
blood (water) during six stages, namely, incision, retraction, direction,
identification, packing, and postpacking. Six fully credentialed surgeons
performed the same task as 12 military medical technicians who were randomized to
remotely telementored (RTM) (n = 7) or unmentored (UTM) (n=5) real-time guidance
by a trauma surgeon. RESULTS: There were no significant differences in fluid loss
between the surgeons and the UTM group or between the UTM and RTM groups.
However, when comparing the RTM group with the surgeons, there was significantly
more total fluid loss (p = 0.001) and greater loss during the identification (p =
0.002), retraction (p = 0.035), direction (p = 0.014), and packing(p = 0.022)
stages. There were no significant differences in fluid loss after packing between
the groups despite differences in the number of sponges used; RTM group used more
sponges than the surgeons and significantly more than the UTM group (p = 0.048).
However, mentoring significantly increased self-assessed nonsurgeon procedural
confidence (p = 0.004). CONCLUSION: Perihepatic packing of an exsanguinating
liver hemorrhage model was readily performed by military medical technicians
after a focused briefing. While real-time telementoring did not improve fluid
loss, it significantly increased nonsurgeon procedural confidence, which may
augment the feasibility of the concept by allowing them to undertake
psychologically daunting procedures.
PMID- 26422333
TI - Development of dendritic form and function.
AB - The nervous system is populated by numerous types of neurons, each bearing a
dendritic arbor with a characteristic morphology. These type-specific features
influence many aspects of a neuron's function, including the number and identity
of presynaptic inputs and how inputs are integrated to determine firing
properties. Here, we review the mechanisms that regulate the construction of cell
type-specific dendrite patterns during development. We focus on four aspects of
dendrite patterning that are particularly important in determining the function
of the mature neuron: (a) dendrite shape, including branching pattern and
geometry of the arbor; (b) dendritic arbor size;
PMID- 26422334
TI - Optical Biopsy of Bladder Cancer Using Crowd-Sourced Assessment.
PMID- 26422335
TI - Older type 2 diabetic patients are more likely to achieve glycaemic and
cardiovascular risk factors targets than younger patients: analysis of a primary
care database.
AB - BACKGROUND: Older subjects with type 2 diabetes mellitus (T2DM) have differential
characteristics compared with middle-aged or younger populations, and require
tailored management of the disease. AIMS: To evaluate how clinical
characteristics, degree of control of glycaemia and cardiovascular risk factors,
presence of chronic complications and treatments differ between older T2DM
patients and younger adults. METHODS: Cross-sectional study using data from a
population-based electronic database. We retrieved data from 318,020 patients >=
30 years diagnosed with T2DM, attended during 2011 in primary care centres in
Catalonia, Spain. We performed descriptive and comparative analyses stratified by
gender and age subgroups: <= 65, 66-75, 76-85 and >85 years. RESULTS: Both men
and women across older age subgroups (> 65 years) had longer diabetes duration
than younger adults (8.0 vs. 5.6 in men and 8.4 vs. 6.9 years in women; p <
0.001), but better glycaemic control (mean glycated haemoglobin 7.1 vs. 7.7 in
men and 7.1 vs. 7.4 in women; p < 0.001), and better combined control of
different cardiovascular risk factors (p < 0.001). Moreover, older patients were
more likely to achieve glycaemic targets irrespective of having cardiovascular
disease. The use of oral antidiabetics decreased with increasing age, and insulin
in monotherapy was more frequently prescribed among patients in the older age
subgroups. Diabetes-related complications were more frequent in men of all group
ages. In the older age subgroups, patients of both sexes had a longer duration of
T2DM but better glycaemic control. In this context, the prevalence of diabetic
retinopathy decreased unexpectedly with increasing age. CONCLUSION: Control of
glycaemia and cardiovascular risk factors was better among older T2DM patients.
There is a need for prospective studies to quantify the weight of risk factors in
each complication to adapt the therapeutic and care approaches in elderly people.
PMID- 26422336
TI - Improved child behavioural and emotional functioning after Circle of Security 20
week intervention.
AB - This study examined the efficacy of the attachment-based Circle of Security 20
week intervention in improving child behavioural and emotional functioning.
Participants were 83 parents of children (1-7 years) referred to a clinical
service with concerns about their young children's behaviour. Parents (and
teachers, when available) completed questionnaires assessing child protective
factors, behavioural concerns, internalizing and externalizing problems, prior to
and immediately after the intervention. The following were considered as
potential moderators: child gender and age, parent representations, reflective
functioning, child attachment indices and severity of presenting problems, prior
to treatment. Results showed significant improvement for parent ratings of child
protective factors, behavioural concerns, internalizing and externalizing
symptoms, all ps < .05, and children with more severe problems showed most
improvement. Teachers also reported improvements, but change was significant only
for externalizing problems (p = .030). Findings suggest Circle of Security is
effective in improving child behavioural and emotional functioning in clinically
referred children aged 1-7 years.
PMID- 26422337
TI - Transforming Quality Improvement Into Evidence-Based Quality Improvement: A Key
Solution to Improve Healthcare Outcomes.
PMID- 26422338
TI - Pulmonary sarcoidosis in the context of a telaprevir-based triple therapy for
hepatitis C.
PMID- 26422340
TI - Functional outcomes of arthroscopic treatment of lateral epicondylitis.
AB - OBJECTIVE: The aim of this study is to evaluate the functional results of
arthroscopic lateral epicondylitis (LE) treatment in patients in whom
conservative treatment proved insufficient. METHODS: Between 2011-2014, 29
patients with LE (15 women, 14 men; mean age: 46 years; range: 33-79) who
received at least 6 months of conservative treatment methods and did not achieve
full recovery and thus underwent arthroscopic surgery were included in this
study. RESULTS: One patient was excluded from the functional assessment. Mean
follow-up was 20.5 months (range: 7-42). Mean preoperative and postoperative
Disabilities of the Arm, Shoulder and Hand (DASH) scores were 81.1+/-17.5 and
34.7+/-26.8 (p<0.0001), respectively, and Mayo Elbow Performance Scores (MEPS)
were 48.5+/-11.5 and 101.2+/-22.9 (p<0.0001), respectively. Twenty-one patients
(75%) were satisfied with the functional outcome. CONCLUSION: As a result, LE
treated with the arthroscopic method, with its low complication rate, successful
degenerated tendon debridement, and decortication of the lateral epicondyle, is a
useful method for intervention in pathologies such as annular plica, loose body,
synovial hypertrophy, and radiocapitellar chondropathy.
PMID- 26422339
TI - Comparison of extracorporeal shock wave therapy in acute and chronic lateral
epicondylitis.
AB - OBJECTIVE: The aim of this study is to evaluate and compare the results of
extracorporeal shock wave therapy (ESWT) in the treatment of acute (<3 months)
lateral epicondylitis (LE) and chronic (>6 months) LE groups. METHODS: Fifty-four
patients who were diagnosed with LE and treated with BTL-5000 SWT Power (BTL
Turkiye Medikal Cihazlar, Ankara, Turkey) ESWT were included in the study. Twenty
four patients who had symptoms for <3 months were defined as the acute LE group
(Group A), and 30 patients who had symptoms for >6 months were defined as the
chronic LE group (Group B). All cases were evaluated pretherapy and at Weeks 2,
12, and 24 posttherapy according to pain while resting, pain while stretching,
pain when pressed, pain while lifting chair, pain while working, nighttime pain
on LE zone. RESULTS: Almost all values in both Group A and Group B were
significantly improved at Weeks 2, 12, and 24 compared to the baseline values.
CONCLUSION: ESWT is equally effective in the treatment of acute LE and chronic
LE. In addition, the current data suggest the progression of LE cases from acute
phase to chronic phase may be prevented by treatment with ESWT.
PMID- 26422341
TI - The triangle between the anterior and posterior cruciate ligaments: an
arthroscopic anatomy study.
AB - OBJECTIVE: The goal of anterior cruciate ligament (ACL) reconstruction is to
place the graft in closest proximity to the native ACL anatomy. This study aims
to examine the angular relation between intact anterior and posterior cruciate
ligaments (PCL) from an arthroscopic perspective. METHODS: Forty patients (20
male, 20 female) with a mean age of 35.12 (range: 18-40) years that underwent
knee arthroscopy for reasons other than ACL rupture were included in the study.
Following diagnostic examination and repair of the primary pathology, the
triangle between ACL and PCL was seen at different flexion degrees of the knee
joint (120, 90, 60, and 30 degrees ) through standard anterolateral (AL) and
anteromedial (AM) portals. The narrow top angle of the triangle between the long
intersecting axes of ACL and PCL was measured using recorded images by 3 blind
observers. RESULTS: The average ACL-PCL angle was 61 degrees , (standard
deviation+/-2 degrees ) at 90 degrees of knee flexion. The angles were narrower
when viewed through the AM portal. The degree of the angles was not affected by
age, sex, body mass index (BMI), or the side (right or left) on which the
procedure was performed. There was good-to-excellent intra- and interobserver
reliability. CONCLUSION: The angular relation between intact ACL and PCL has the
potential to provide a better view of the anatomy during arthroscopic ACL
surgery. To perform better anatomic reconstructions, it is important to create a
60 degrees angle between the ACL graft and PCL (as viewed through AL portal) at
90 degrees of knee flexion.
PMID- 26422342
TI - Does the anteromedial portal provide clinical superiority compared to the
transtibial portal in anterior cruciate ligament reconstruction in
nonprofessional athletes in short-term follow-up?
AB - OBJECTIVE: Two drilling techniques of the femoral tunnel are commonly used in
anterior cruciate ligament (ACL) reconstruction: through the transtibial (TT)
portal or through the anteromedial (AM) portal. The aim of the present study is
to investigate the radiological and clinical outcomes of arthroscopic single
bundle ACL reconstruction using AM and TT portal techniques for drilling the
femoral tunnel in nonprofessional athletes. METHODS: A retrospective review was
made of 44 nonprofessional athletes undergoing ACL reconstruction using AM and TT
techniques between 2011-2013. The femoral tunnel clock position on axial magnetic
resonance imaging (MRI) and the anterior-posterior position of the tibial tunnel
on sagittal-cut MRI scan were measured. Radiological femoral tunnel and tibial
tunnel anterior-posterior inclination angles were assessed. At final follow-up,
the Lachman test and pivot-shift test were used in the evaluation of the anterior
posterior stability of the knee and the rotational stability of the knee. For
clinical and functional evaluation, the modified Cincinnati knee grading system,
Lysholm knee scoring scale, and International Knee Documentation Committee (IKDC)
form were used. RESULTS: No statistically significant difference was determined
between the groups in terms of patient age, follow-up period, gender, and
affected side distribution. There were 6 outliers in the TT group due to the
clock face position. The mean femoral tunnel inclination angle was 31.07 degrees
+/-8.44 degrees in the AM group and 19.02 degrees +/-8.93 degrees in the TT
group. The tibial tunnel inclination angle was 21.08 degrees +/-5.42 degrees in
the TT group and 16.58 degrees +/-7.02 degrees in the AM group. A statistically
significant difference was determined between the 2 groups. No statistically
significant difference was observed between the 2 groups in terms of Lachman
test, pivot-shift test, Lysholm score, IKDC score, and modified Cincinnati score
results. CONCLUSION: The AM technique has no clinical superiority compared to the
TT technique in ACL reconstruction in nonprofessional athletes.
PMID- 26422343
TI - Psychiatric and functional evaluation of professional athletes following anterior
cruciate ligament reconstruction.
AB - OBJECTIVE: The aim of this study is to evaluate early phase depression and
anxiety in the proffessional athletes who underwent anterior cruciate ligament
(ACL) reconstruction and compare them with the functional improvement of knee.
METHODS: Thirty-eight patients (35 males, 3 females; mean age+/-SD: 26.84+/-8.03)
were included in this study. Measurements were obtained immediately following the
operation and at Week 6 of postoperative rehabilitation. Depression and anxiety
symptoms were evaluated by the Hospital Anxiety and Depression Scale (HADS), and
knee function was evaluated by Lysholm Knee Scoring Scale (LKSS). RESULTS: Change
in total LKSS scores from the time of admission (56.4+/-20.2) to the end of the
sixth week (78.7+/-13.8) was significant (t=-8.21, p<0.001). Neither the HADS
depression nor the HADS anxiety scores were above the cutoff values in the 2
assessments. Significant difference was noted in HADS anxiety scores between the
time of admission (6.21+/-3.50) and at the sixth week (5.33+/-3.33) (t=2.02,
p=0.05). However, HADS depression scores were not statistically different between
the 2 evaluations (5.95+/-3.68 and 5.35+/-3.50 at admission and Week 6 week,
respectively) (t=1.07, p=0.29). Changes between the 2 LKSS and HADS anxiety
assessments were negatively correlated (r=-0.49, p=0.002), but there no
correlation was detected between the total LKSS and HADS score changes.
CONCLUSION: The decline of the signs of anxiety and depression at the sixth week
of rehabilitation indicate that proper rehabilitation positively affects the
emotional status of ACL reconstruction patients.
PMID- 26422344
TI - Effects of two different continuous passive motion protocols on the functional
activities of total knee arthroplasty inpatients.
AB - OBJECTIVE: The aim of this study was to compare the effects of two different
continuous passive motion (CPM) application protocols (low- and high-angle) on
the early phase functional activities of total knee arthroplasty inpatients.
METHODS: The study included 170 patients who underwent primary TKA. While 84 of
the TKA patients underwent low-angle CPM application, 86 of the patients
underwent high-angle CPM application. The patients' functional activities were
compared using the Iowa Level of Assistance Scale (ILAS), gait speeds using the
Iowa Ambulation Velocity Scale (IAVS), knee scores using the Hospital for Special
Surgery (HSS) Knee Score, and the duration of hospital stays with the Visual
Analog Scale (VAS) preoperatively and on postoperative Day 2, Day 6, and at
discharge. RESULTS: It was found that patients in the high-angle group had lower
pain levels than did the patients in the low-angle group postsurgery (p<0.05).
Patients in the high-angle group achieved their functional activities more
independently on postoperative Day 2, Day 6, and at discharge than did the
patients in the low-angle group (p<0.05). However, gait speed of patients in the
former group was lower than that of the patients in the latter group (p<0.05).
CONCLUSION: Although low-angle CPM application produced better results in terms
of gait speed following TKA, the high-angle CPM application was superior in terms
of independence levels of functional activities in the early postsurgery period.
This result suggests that the appropriate use of rehabilitation methods such as
CPM applications may guide clinicians to increase patients' level of
independence.
PMID- 26422345
TI - Total knee arthroplasty after osseous ankylosis of the knee joint.
AB - OBJECTIVE: A knee fusion is associated with considerable restrictions, including
the inability to sit properly, use public transportation, and climb stairs. The
purpose of this study is to report and discuss our cases of spontaneous ankylosed
knees which were taken down and underwent total knee arthroplasty (TKA). METHODS:
Six patients who experienced spontaneous ankylosis of the knee undergoing
conversion to TKA between 2003-2012 were enrolled retrospectively in this study.
The etiology was childhood pyogenic arthritis in 2 patients, intraarticular
fractures in 2, gunshot in 1, and juvenile rheumatoid arthritis in 1. The
clinical data were recorded with the use of the Hospital for Special Surgery
(HSS) knee rating system, Western Ontario and McMaster Questionnaire (WOMAC), and
Visual Analog Scale (VAS), preoperatively and postoperatively at final follow-up.
RESULTS: The average follow-up time was 86 months (range: 22-126 months). At the
final follow-up, the average range of active flexion was 85 degrees (range: 75
95 degrees ). Postoperative average HSS knee rating system was improved from 19.5
(range: 18-22) to 57.49 (range: 46-80), WOMAC was improved from 39.75 (range:
36.4-43) to 62.41 (range: 50.8-74.5). VAS was improved from 9.5 (range: 7-9) to
2.8 (range: 2-4). A pyogenic infection developed in 2 patients; 1 was managed by
debridement, and 1 was managed by arthrodesis 2 years later. CONCLUSION: The
ability to walk and sit in a normal fashion is of great importance for patients.
With good preoperative planning and careful handling, gratifying results are
possible with TKA.
PMID- 26422346
TI - Analysis of the reliability and validity of the Turkish version of the
intermittent and constant osteoarthritis pain questionnaire.
AB - OBJECTIVE: The aim of this study was to analyze the validity and reliability of
the Turkish version (ICOAP-TR) of the intermittent and constant osteoarthritis
pain (ICOAP) questionnaire in patients with knee osteoarthritis (OA). METHODS:
Thirty-eight volunteer patients diagnosed with knee OA answered the questionnaire
twice with an interval of 2-4 days. The reliability of the measurement was
assessed using Cronbach's alpha coefficient and intraclass correlation (ICC) for
test-retest reliability. Criterion validity was tested against the Western
Ontario and McMaster Universities Arthritis Index (WOMAC) pain score and visual
analog scale (VAS) designed to assess the perceived discomfort rated by the
patient. RESULTS: Test-retest reliability was found to be ICC=0.942 for total
score, 0.902 for constant pain subscale, and 0.945 for intermittent pain
subscale. Internal consistency was tested using Cronbach's alpha and was found to
be 0.970 for total score, 0.948 for constant pain subscale, and 0.972 for
intermittent pain subscale. For criterion validity, the correlation between the
total score of ICOAP-TR and WOMAC pain subscale was r=0.779 (p<0.05), and
correlation between total score of ICOAP-TR and VAS was r=0.570 (p<0.05).
CONCLUSION: The ICOAP-TR is a reliable and valid instrument to be used with
patients with knee OA.
PMID- 26422347
TI - Single-stage posterior transforaminal lumbar interbody fusion, debridement,
limited decompression, 3-column reconstruction, and posterior instrumentation in
surgical treatment for single-segment lumbar spinal tuberculosis.
AB - OBJECTIVE: The aim of this study is to determine the feasibility and efficacy of
surgical management of single-segment lumbar spinal tuberculosis (TB) by using
single-stage posterior transforaminal lumbar interbody fusion, debridement,
limited decompression, 3-column reconstruction, and posterior instrumentation.
METHODS: Seventeen cases of single-segment lumbar TB were treated with single
stage posterior transforaminal lumbar interbody fusion, debridement, limited
decompression, 3-column reconstruction, and posterior instrumentation. The mean
follow-up was 36.9 months (range: 24-62 months). The kyphotic angle ranged from
15.2-35.1 degrees preoperatively, with an average measurement of 27.8 degrees .
The American Spinal Injury Association (ASIA) score system was used to evaluate
the neurological deficits and erythrocyte sedimentation rate (ESR) used to judge
the activity of TB. RESULTS: Spinal TB was completely cured in all 17 patients.
There was no recurrent TB infection. The postoperative kyphotic angle was 6.6
10.2 degrees , 8.1 degrees in average, and there was no significant loss of the
correction at final follow-up. Solid fusion was achieved in all cases.
Neurological condition in all patients was improved after surgery. CONCLUSION:
Single-stage posterior transforaminal lumbar interbody fusion, debridement,
limited decompression, 3-column reconstruction, and posterior instrumentation can
be a feasible and effective method the in treatment of single-segment lumbar
spinal TB.
PMID- 26422348
TI - Safety and feasibility of lumbar spine for intralaminar screw fixation: a
computed tomography-based morphometric study.
AB - OBJECTIVE: The use of intralaminar screws (ILS) in spinal surgery has experienced
a recent increase in popularity. The aim of this study is to define the
morphological parameters of the lumbar laminas so that guidance may be defined
for ILS placement. METHODS: The study involved the evaluation of lumbar computed
tomography (CT) images of patients. Two hundred thirty-five patients (127 male,
108 female) were included in the study. The mean patient age was 44.2 years (19
78 years). The measured parameters of the lamina were the transverse inner
diameter, transverse outer diameter (lamina width), lamina length, subdural space
(safe zone), and spinolaminar angle for each lumbar level (L1-L5). RESULTS: The
mean transverse outer diameter (L1-L5) ranged from 7.2-7.8 mm, and mean
transverse inner diameter ranged from 2.5-3.0 mm. The lamina of L3 had the
largest width and the lamina of L1 and L5 the smallest. The mean lamina length
was 26.6 mm, ranging from 21.0-34.0 mm, and the mean spinolaminar angle was 124.7
degrees , ranging from 111-135 degrees . The L1 level had the shortest mean
lamina length and L4 the lowest spinolaminar angle. Mean subdural space (safe
zone), which was narrowest at the L5 level, was 2.4 mm, ranging from 1.3-3.6 mm.
CONCLUSION: ILS of the appropriate size (3.5-4.5 mm) and length (20 and 25 mm)
can be used safely in the lumbar spine. However, further biomechanical studies
should be performed to measure strength of the fixation.
PMID- 26422349
TI - A combined procedure for irreducible dislocation of patella in children with
ligamentous laxity: a preliminary report.
AB - OBJECTIVE: Irreducible patellar dislocation accompanying ligamentous laxity is
rarely seen in pediatric patients. The most common complaints due to this
condition are inability to walk, delayed walking, and difficulties with
orthotics. The purpose of this retrospective study is to describe a novel
surgical technique to treat dislocated patella in patients with symptomatic
ligamentous laxity. METHODS: Fourteen knees of 9 patients operated on by a single
surgeon between 2009-2012 were included in the study. The tensor fascia was
divided into 2 strips, and these strips were passed via the joint and sutured to
themselves. The combined procedure additionally includes lateral capsular
release, vastus lateralis (VL) resection, medial capsular plication, and Z-plasty
of the rectus femoris (RF) tendon. RESULTS: Mean age at the time of surgery was
6.9+/-3.3 years (range: 4-13 years). The mean follow-up was 37.6+/-0.9 months
(range: 26-49 months). Patellofemoral instability was restored for all patients
by using combined surgical technique. Patellar lateralization developed in 2
patients, in whom stability was obtained via secondary medial plication.
CONCLUSION: Our results show that this combined surgical procedure stabilizes the
knee and treats patellar dislocation accompanying ligamentous laxity in pediatric
patients.
PMID- 26422350
TI - Comparison between knot and Winograd techniques on ingrown nail treatment.
AB - OBJECTIVE: The aim of this study was to compare the Winograd and knot techniques
based on efficiency, complication rate, surgery time, and amount of local
anesthetic required. This study also aimed to determine the etiology of ingrown
nails, whether due to involvement of the nail or soft tissue. METHODS: Seventy
five patients with a total of 90 ingrown nails (stages 2 and 3) who presented at
our clinic between 2012-2014 were included in this study. Patients were divided
into 2 groups: those treated with the knot technique and those treated with the
Winograd technique. Patients in both groups were evaluated for the amount of
local anesthetic required, intraoperative pain, effectiveness of
preventing/stopping hemorrhage, surgery time, complications, postoperative nail
size, recurrence, nail deformities, and secondary surgery rates. RESULTS: The
mean surgical time, relapse rate, number of additional surgeries required, and
amount of local anesthetic were significantly greater in the Winograd group than
in the knot group. The mean nail diameter was significantly decreased, with a
mean of 3 mm in the Winograd group. No statistically significant differences were
found between the groups in the incidence of infection, intraoperative pain,
hematoma, or nail deformity. CONCLUSION: This study demonstrated that the knot
technique, consisting of wedge excision of soft tissue without affecting the nail
itself, is a simple technique to treat ingrown nails with a lower complication
rate and shorter surgical time. We believe that successful treatment of ingrown
nails depends only on excision of soft tissue, with no need to operate on the
nail bed.
PMID- 26422351
TI - Effect of platelet-rich plasma for treatment of Achilles tendons in free-moving
rats after surgical incision and treatment.
AB - OBJECTIVE: The purpose of this study is to investigate, both histopathologically
and biomechanically, the effect of platelet-rich plasma (PRP) on surgically
repaired Achilles tendon rupture recovery in rats. METHODS: The study included 25
17-month-old male Sprague-Dawley rats with an average weight of 500-550 g. Five
rats were used as donors, while 20 rats were separated as PRP group (n=10) and
control group (n=10). The Achilles tendons of the rats were cut transversely, and
PRP was administered to the PRP group, while the control group received serum
physiologically to create the same surgical effect. In previous studies, it was
shown that this serum does not affect tendon recovery. Fifteen and 30 days post
treatment, the rats were sacrificed, and their Achilles tendons were extracted
and examined histopathologically and biomechanically. RESULTS: Based on the
obtained findings, it was observed that the histopathologic Movin and Bonar
scores of PRP group on the 15th and 30th day post-treatment were significantly
lower than those of the control group (p=0.019, p=0.017, respectively), while no
significant difference was found in maximum force (Fmax) values in biomechanical
measures on the 15th and 30th day post-treatment. CONCLUSION: It is thought that
PRP use in Achilles tendon ruptures positively affects histopathological recovery
in the early period, but that it does not produce the same biomechanical effect.
We believe that PRP use for qualified tendon recovery is histopathologically
beneficial.
PMID- 26422352
TI - Reliability of threaded locking screws.
AB - OBJECTIVE: A frequent problem for interlocking nailing that affects the treatment
of the fracture is locking screw deformation. The aim of this study is to
determine whether bending resistance is different between high, low, and
unthreaded locking screws of interlocking femoral nails. METHODS: Ninety screws
were used in this experimental study, with 10 screws used in each of 9 groups.
Three-point bending tests were performed on 6 groups of 5 mm screws (titanium,
stainless steel, crossed with unthreaded, low threaded, and high threaded) and
the same 3 thread types of 5.5 mm stainless steel screws in a 30-mm inner
diameter steel tube, imitating the level of the lesser trochanter. An axial
compressor was used to determine the yield points for permanent deformation in
the locking screws by way of 3-point bending tests. RESULTS: The mean yield point
value of the 3-point bending tests of 5-mm low threaded stainless steel locking
screws was 2071 N, 53% less than that of unthreaded screws (3169 N). The mean
yield point value of 5-mm high threaded stainless steel locking screws was 556 N,
272% less than that of low threaded screws (2071 N). CONCLUSION: To avoid locking
screw deformation, high threaded screws must not be used as locking screws. In
cases of unreliable patients, 5-mm low threaded screws should not be used in the
nailing of comminuted or oblique femur shaft fractures. All 5-mm unthreaded
screws and 5.5-mm low threaded stainless steel screws can be used safely in full
weight-bearing conditions of unreliable patients.
PMID- 26422353
TI - Effects of intraperitoneal hydrogen injection on nitric oxide synthase mRNA and
malondialdehyde following limb ischemia-reperfusion in rabbits.
AB - OBJECTIVE: The purpose of this study was to investigate the effects of
intraperitoneal hydrogen (H2) injection on the mRNA expression levels of
inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase
(eNOS) as well as the serum malondialdehyde (MDA) level in a rabbit model of limb
ischemia-reperfusion (I/R)-induced skeletal muscle injury. METHODS: To establish
the hind limb I/R animal model, 30 rabbits were randomly assigned to one of 3
groups: sham, I/R, and ischemia-reperfusion + H2 (IRH). An intraperitoneal
injection of H2 was given to the IRH group, while an equivalent amount of air was
given to the sham and I/R groups. At 3, 6, 12, and 24 h after reperfusion, serum
MDA level as well as skeletal muscle iNOS and eNOS mRNA expression levels were
determined. RESULTS: Both iNOS mRNA expression and serum MDA levels were higher
in the I/R group than the sham group (p<0.01) and lower in the IRH group than the
I/R group (p<0.01, p<0.05, respectively) at various time points after
reperfusion. The eNOS mRNA expression level exhibited no significant difference
between the I/R and sham groups after reperfusion but was significantly higher in
the IRH group than in the sham group (p<0.01, p<0.05, respectively). CONCLUSION:
During the I/R process, the expression of iNOS mRNA was up-regulated along with
an increase in MDA. Intraperitoneal injection of H2 can down-regulate iNOS mRNA
expression and up-regulate eNOS mRNA expression in the I/R process, suggesting a
protective effect of H2 in I/R-induced skeletal muscle injury.
PMID- 26422354
TI - A mechanically locked knee joint due to free-floating flake-shaped rice bodies: a
case report.
AB - Originating from the synovium, multiple free-floating intra-articular particles,
called rice bodies, typically resemble cartilage and have a fibrin structure.
While the etiology of rice body formation is unclear, they often occur in
rheumatoid arthritis and other seronegative arthropathies; they also occur in
tuberculosis, though the incidence is much lower. They are often encountered by
rheumatologists or clinical orthopedists. A 33-year-old female who suffered from
occasional swelling and pain of her left knee for 3 months was admitted with a
mechanically locked knee. Free-floating rice bodies were identified on magnetic
resonance imaging (MRI), and arthroscopic intervention was performed for
diagnostic and therapeutic purposes. After the removal of all bodies and effusion
with mechanical irrigation, an arthroscopic subtotal synovectomy was performed.
PMID- 26422355
TI - Parvovirus B19-induced acute bilateral carpal tunnel syndrome in twin girls.
AB - We describe 2 cases of 6-year-old twin girls presenting with acute carpal tunnel
syndrome (CTS) associated with human parvovirus B19 (HPV-B19) infection, as
evidenced by serological data and detection of HPV-B19 DNA in blood with use of
polymerase chain reaction (PCR). To our knowledge, this is the first time that
HPV-B19 infection has been suggested as the causal agent of simultaneous acute
bilateral CTS in twins, thus presenting the possibility that similar immunologic
responses can be observed in twins during viral infections.
PMID- 26422356
TI - Omentum and reverse turnover latissimus dorsi musculocutaneous flap for the
treatment of cerebrospinal fluid fistula.
AB - Conventional procedures can usually prevent cerebrospinal fluid (CSF) leakages,
but they may not work for complicated cases. In this case presentation, we
demonstrated the effectiveness of combined omental and latissimus dorsi
musculocutaneous flaps for management of difficult CSF fistula. A reverse
turnover latissimus dorsi musculocutaneous flap and omental flap were transferred
for reconstruction of the posterior wound and CSF leakage. The omental flap
component was used for CSF absorption, and the latissimus dorsi muscle component
was used for obliteration of the dead space, covering of the exposed bone, and
tension-free closure of the wound. The wound healed dramatically, with no
observed severe donor site morbidity. The patient has been followed for 30 months
with no evidence of CSF leakage and no pseudomeningocele formation, which was
confirmed by magnetic resonance imaging (MRI). Although this is a case
presentation, we can say that the combination of the omental and musculocutaneous
flaps allow effective treatment and prevention of CSF fistulas in selected high
risk patients and provide durable coverage of complex spinal wounds.
PMID- 26422357
TI - Comment on: Functional outcomes of minimal invasive percutaneous plate
osteosynthesis (MIPPO) in humerus shaft fractures: a clinical study.
PMID- 26422358
TI - Authors' reply.
PMID- 26422360
TI - Impact of glucocerebrosidase mutations on motor and nonmotor complications in
Parkinson's disease.
AB - Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease
(GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's
disease (PD). This study examined the impact of GBA mutations on the longitudinal
clinical course of PD patients by retrospective cohort design. GBA-coding regions
were fully sequenced in 215 PD patients and GD-associated GBA mutations were
identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to
develop dementia, psychosis, wearing-off, and dyskinesia were examined. Survival
time analysis followed a maximum 12-year observation (median 6.0 years),
revealing that PD patients with GD-associated mutations developed dementia and
psychosis significantly earlier than those without mutations (p < 0.001 and p =
0.017, respectively). Adjusted hazard ratios of GBA mutations were 8.3 for
dementia (p < 0.001) and 3.1 for psychosis (p = 0.002). No statistically
significant differences were observed for wearing-off and dyskinesia between the
groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography
pixel-by-pixel analysis revealed that regional cerebral blood flow was reduced in
the bilateral parietal cortex, including the precuneus of GD-associated mutant PD
patients, compared with matched PD controls without mutations.
PMID- 26422359
TI - Suspected non-AD pathology in mild cognitive impairment.
AB - We aim to better characterize mild cognitive impairment (MCI) patients with
suspected non-Alzheimer's disease (AD) pathology (SNAP) based on their
longitudinal outcome, cognition, biofluid, and neuroimaging profile. MCI
participants (n = 361) from ADNI-GO/2 were designated "amyloid positive" with
abnormal amyloid-beta 42 levels (AMY+) and "neurodegeneration positive" (NEU+)
with abnormal hippocampal volume or hypometabolism using fluorodeoxyglucose
positron emission tomography. SNAP was compared with the other MCI groups and
with AMY- controls. AMY-NEU+/SNAP, 16.6%, were older than the NEU- groups but not
AMY- controls. They had a lower conversion rate to AD after 24 months than
AMY+NEU+ MCI participants. SNAP-MCI participants had similar amyloid-beta 42
levels, florbetapir and tau levels, but larger white matter hyperintensity
volumes than AMY- controls and AMY-NEU- MCI participants. SNAP participants
performed worse on all memory domains and on other cognitive domains, than AMY
NEU- participants but less so than AMY+NEU+ participants. Subthreshold levels of
cerebral amyloidosis are unlikely to play a role in SNAP-MCI, but pathologies
involving the hippocampus and cerebrovascular disease may underlie the
neurodegeneration and cognitive impairment in this group.
PMID- 26422361
TI - DNA methylation levels of alpha-synuclein intron 1 in the aging brain.
AB - DNA methylation patterns change with age, and aging itself is a major confounding
risk factor for Parkinson's disease (PD). Duplication and triplication, that is,
increased expression of the alpha-synuclein (SNCA) gene, cause familial PD, and
demethylation of SNCA intron 1 has been shown to result in increased expression
of SNCA. We thus hypothesized that age-related alterations of SNCA methylation
might underly the increased susceptibility toward PD in later life. The present
study sought to determine (1) whether alterations of SNCA intron 1 methylation
occurred during aging, (2) whether the methylation pattern differed between men
and women, and (3) whether purified neurons compared with non-neuronal cells
exhibited different methylation patterns. The analysis of DNA from brain tissue
and fluorescence activated cell sorting-sorted purified neurons of 41 individuals
revealed only a minor increase of SNCA intron 1 DNA methylation levels in
presumably healthy individuals during aging but no significant difference between
men and women. Interestingly enough, methylation of SNCA intron 1 was higher in
neurons compared with non-neuronal cells, although non-neuronal cells express
lower levels of SNCA. Therefore, the normal pattern of SNCA methylation during
aging should not result in increased expression of alpha-synuclein protein. It is
thus likely that additional, yet not identified, mechanisms contribute to the
tissue specificity of SNCA expression and the presumed dysregulation in PD.
PMID- 26422362
TI - Probable novel PSEN2 Pro123Leu mutation in a Chinese Han family of Alzheimer's
disease.
AB - We describe a probably novel mutation in exon 5 of the presenilin 2 gene
(Pro123Leu) in a Chinese familial early-onset Alzheimer's disease, which
clinically manifests as progressive memory loss, cognitive impairment,
parkinsonism, and myoclonic jerks. Clinical and neuroimaging examination, target
region capture, and high-throughput sequencing were performed in a family of 4
generations. Cerebral perfusion and glucose metabolism were evaluated using
arterial spin labeling perfusion magnetic resonance imaging and (18)F
fludeoxyglucose positron emission tomography, respectively. Target region capture
sequencing yielded a novel missense mutation at codon 123 (P123L) which is a
heterozygous C to T point mutation at position 368 (c.368C>T) in exon 5 of the
presenilin 2 leading to a proline-to-leucine substitution. The results were also
identified by Sanger sequencing in 7 family members but not in the other 9
unaffected family members and 100 control subjects. This mutation is probably
pathogenic and is the first of its kind reported in an early-onset familial AD
associated with atypical symptom presentation.
PMID- 26422363
TI - Rapid and Versatile Photonic Annealing of Graphene Inks for Flexible Printed
Electronics.
AB - Intense pulsed light (IPL) annealing of graphene inks is demonstrated for rapid
post-processing of inkjet-printed patterns on various substrates. A conductivity
of ~25,000 S m(-1) is achieved following a single printing pass using a
concentrated ink containing 20 mg mL(-1) graphene, establishing this strategy as
a practical and effective approach for the versatile and high-performance
integration of graphene in printed and flexible electronics.
PMID- 26422364
TI - The effect of animal health compensation on 'positive' behaviours towards exotic
disease reporting and implementing biosecurity: A review, a synthesis and a
research agenda.
AB - With an increasing burden on public sector budgets, increased responsibility and
cost sharing mechanisms for animal diseases are being considered. To achieve
this, fiscal and non-fiscal intervention policies need to be designed such that
they consistently promote positive disease risk management practices by animal
keepers. This paper presents a review of the available evidence towards whether
and how the level and type of funding mechanism affects change within biosecurity
behaviours and the frequency of disease reporting. A Nuffield Health Ladder of
Interventions approach is proposed as a way to frame the debate surrounding both
current compensation mechanisms and how it is expected to change behaviour.
Results of the review reveal a division between economic modelling approaches,
which implicitly assume a causal link between payments and positive behaviours,
and socio-geographic approaches which tend to ignore the influence of
compensation mechanisms on influencing behaviours. Generally, economic studies
suggest less than full compensation rates will encourage positive behaviours, but
the non-economic literature indicate significant variation in response to
compensation reflecting heterogeneity of livestock keepers in terms of their
values, goals, risk attitudes, size of operation, animal species and production
chain characteristics. This may be of encouragement to Western Governments
seeking to shift cost burdens as it may induce greater targeting of non-fiscal
mechanisms, or suggest more novel ways to augment current compensation mechanisms
to both increase responsibility sharing and reduce this cost burden. This review
suggests that a range of regulatory, fiscal and nudging policies are required to
achieve socially optimal results with respect to positive behaviour change.
However, the lack of directly available evidence which proves these causal links
may hinder progress towards this optimal mixture of choice and non-choice based
interventions.
PMID- 26422365
TI - [Customized and non-customized French intrauterine growth curves. I -
Methodology].
AB - OBJECTIVES: We developed intrauterine growth references, called EPOPe curves, in
line with recommendations for screening of intra-uterine growth restriction
issued in 2013 by the French College of Obstetricians and Gynecologists.
POPULATION AND METHODS: Using the French Perinatal Survey (FPS) 2010, we adapted
the methodology developed by Gardosi (1) to model intrauterine growth and its
distribution and (2) to adjust for physiological fetal and maternal factors
influencing fetal weight. Based on this model, 3 reference curves (unadjusted,
adjusted for fetal sex, and adjusted for fetal sex, and maternal height, weight
and parity) were proposed. We applied these models to births in the 2010 FPS and
the French hospital discharge database (PMSI) in 2011-2012. RESULTS: Among
singleton live births in the FPS and the PMSI, the model adjusted for fetal sex
identified 3.2 and 3.3% of births below the 3rd centile respectively, and 10.0
and 10.2% below the 10th. In model adjusted for maternal factors, 4.0% of births
from the FPS 2010 were reclassified, but population rates remained at 3.0 and
10.0%. CONCLUSION: This growth model is appropriate for French births, and allows
for the implementation of a homogeneous definition of small for gestational age
infants during pregnancy and at birth.
PMID- 26422366
TI - A light fingertip touch reduces postural sway in children with autism spectrum
disorders.
AB - This study examined the effects of a light fingertip touch on postural control in
children with autism spectrum disorders (ASD) and typically developing children
(TDC). METHODS: We recruited 16 children with ASD (age=11.041+/-1.275), and 16
TDC (age=10.966+/-1.166 years). A force platform measured postural sway in the
anteroposterior (AP) and mediolateral (ML) directions under light fingertip touch
(LT) and no touch (NT) conditions, with both eyes open (EO) and both eyes closed
(EC). As a summary of the experimental conditions, ML sway was significantly
greater in the ASD group than in the TDC group. Also, results showed a
significant reduction in postural sway in the ML direction in the LT condition
compared with the NT condition. These effects applied to both the EO and EC
conditions. Lastly, the reduction in ML sway between the NT and LT conditions was
significantly greater in the ASD than the TDC group. CONCLUSION: The effects of a
light fingertip touch on reducing postural sway appear more efficient in children
with ASD compared with TDC. These findings suggest that a light fingertip touch
may be of clinical and practical importance, and provides a useful means of
enhancing postural stability in children with ASD.
PMID- 26422367
TI - Gradual Reduction in Sodium Content in Cooked Ham, with Corresponding Change in
Sensorial Properties Measured by Sensory Evaluation and a Multimodal Machine
Vision System.
AB - The European diet today generally contains too much sodium (Na(+)). A partial
substitution of NaCl by KCl has shown to be a promising method for reducing
sodium content. The aim of this work was to investigate the sensorial changes of
cooked ham with reduced sodium content. Traditional sensorial evaluation and
objective multimodal machine vision were used. The salt content in the hams was
decreased from 3.4% to 1.4%, and 25% of the Na(+) was replaced by K(+). The salt
reduction had highest influence on the sensory attributes salty taste, after
taste, tenderness, hardness and color hue. The multimodal machine vision system
showed changes in lightness, as a function of reduced salt content. Compared to
the reference ham (3.4% salt), a replacement of Na(+)-ions by K(+)-ions of 25%
gave no significant changes in WHC, moisture, pH, expressed moisture, the sensory
profile attributes or the surface lightness and shininess. A further reduction of
salt down to 1.7-1.4% salt, led to a decrease in WHC and an increase in
expressible moisture.
PMID- 26422368
TI - Harmony Search Algorithm for Word Sense Disambiguation.
AB - Word Sense Disambiguation (WSD) is the task of determining which sense of an
ambiguous word (word with multiple meanings) is chosen in a particular use of
that word, by considering its context. A sentence is considered ambiguous if it
contains ambiguous word(s). Practically, any sentence that has been classified as
ambiguous usually has multiple interpretations, but just one of them presents the
correct interpretation. We propose an unsupervised method that exploits knowledge
based approaches for word sense disambiguation using Harmony Search Algorithm
(HSA) based on a Stanford dependencies generator (HSDG). The role of the
dependency generator is to parse sentences to obtain their dependency relations.
Whereas, the goal of using the HSA is to maximize the overall semantic similarity
of the set of parsed words. HSA invokes a combination of semantic similarity and
relatedness measurements, i.e., Jiang and Conrath (jcn) and an adapted Lesk
algorithm, to perform the HSA fitness function. Our proposed method was
experimented on benchmark datasets, which yielded results comparable to the state
of-the-art WSD methods. In order to evaluate the effectiveness of the dependency
generator, we perform the same methodology without the parser, but with a window
of words. The empirical results demonstrate that the proposed method is able to
produce effective solutions for most instances of the datasets used.
PMID- 26422369
TI - The Jebsen Taylor Test of Hand Function: A Pilot Test-Retest Reliability Study in
Typically Developing Children.
AB - AIMS: The aim of this pilot study was to evaluate reproducibility of the Jebsen
Taylor Test of Hand Function (JTTHF) in children. METHODS: Eighty-seven typically
developing children 5 to 10 years old were included from five Outside School
Hours Care centers in the Greater Brisbane Region, Australia. Hand function was
assessed on two occasions with a modified JTTHF, then reproducibility was
assessed using Intraclass Correlation Coefficient (ICC [3,1]) and the Standard
Error of Measurement (SEM). RESULTS: Total scores for male and female children
were not significantly different. Five-year-old children were significantly
different to all other age groups and were excluded from further analysis.
Results for 71 children, 6 to 10 years old were analyzed (mean age 8.31 years (SD
1.32); 33 males). Test-retest reliability for total scores on the dominant and
nondominant hands were ICC 0.74 (95% CI 0.61, 0.83) and ICC 0.72 (95% CI 0.59,
0.82), respectively. 'Writing' and 'Simulated Feeding' subtests demonstrated poor
reproducibility. The Smallest Real Difference was 5.09 seconds for total score on
the dominant hand. CONCLUSIONS: Findings indicate good test-retest reliability
for the JTTHF total score to measure hand function in typically developing
children aged 6 to 10 years.
PMID- 26422370
TI - Crystal structures of halohydrin hydrogen-halide-lyases from Corynebacterium sp.
N-1074.
AB - Halohydrin hydrogen-halide-lyase (H-Lyase) is a bacterial enzyme that is involved
in the degradation of halohydrins. This enzyme catalyzes the intramolecular
nucleophilic displacement of a halogen by a vicinal hydroxyl group in halohydrins
to produce the corresponding epoxides. The epoxide products are subsequently
hydrolyzed by an epoxide hydrolase, yielding the corresponding 1, 2-diol. Until
now, six different H-Lyases have been studied. These H-Lyases are grouped into
three subtypes (A, B, and C) based on amino acid sequence similarities and
exhibit different enantioselectivity. Corynebacterium sp. strain N-1074 has two
different isozymes of H-Lyase, HheA (A-type) and HheB (B-type). We have
determined their crystal structures to elucidate the differences in
enantioselectivity among them. All three groups share a similar structure,
including catalytic sites. The lack of enantioselectivity of HheA seems to be due
to the relatively wide size of the substrate tunnel compared to that of other H
Lyases. Among the B-type H-Lyases, HheB shows relatively high enantioselectivity
compared to that of HheBGP1 . This difference seems to be due to amino acid
replacements at the active site tunnel. The binding mode of 1, 3-dicyano-2
propanol at the catalytic site in the crystal structure of the HheB-DiCN complex
suggests that the product should be (R)-epichlorohydrin, which agrees with the
enantioselectivity of HheB. Comparison with the structure of HheC provides a clue
for the difference in their enantioselectivity.
PMID- 26422371
TI - Effects of Dexamethasone and Insulin Alone or in Combination on Energy and
Protein Metabolism Indicators and Milk Production in Dairy Cows in Early
Lactation - A Randomized Controlled Trial.
AB - OBJECTIVES: This study investigated the effects of dexamethasone and insulin,
when administered at 3rd or 10th day of lactation on energy and protein
metabolism in dairy cows. MATERIALS AND METHODS: Two hundred Holstein cows were
enrolled in a randomized controlled clinical trial. The cows were randomly
assigned to receive 1 of 4 treatments at 3 or 10 days in milk: control group, 10
mL i.m. injection of sterile water, group insulin, s.c. injection of 100 units of
insulin, group dexamethasone, i.m. injection of 20 mg of dexamethasone, group
insulin plus dexamethasone, i.m. injection of 20 mg of dexamethasone and 100
units of insulin. The cows randomly assigned to receive the treatments on 3 or 10
days of lactation. Serum samples obtained at the time of enrollment, time of
treatment and at 2, 4, 7 and 14 days after intervention. The sera were analyzed
for beta-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), glucose,
cholesterol, albumin, urea, and aspartate amino transferase (AST). Data were
analyzed using a repeated measures mixed model that accounted for the effects of
parity, body condition score, dystocia, retained placenta, metritis and the
random effect of cow. RESULTS: There was no significant interaction of group of
treatment and time of intervention (day 3 or 10 post-partum) on serum components.
Cows that received insulin or dexamethasone alone or in combination, had lower
BHBA 2 days after treatment compared with control cows, whereas concentrations of
NEFA, were unaffected suggesting that glucocorticoids lipolytic effects do not
appear to be important in healthy cows. AST activities significantly reduced in
cows that received dexamethasone with or without insulin at 2 and 4 days after
treatment. Albumin and urea concentrations 2 days after treatment were higher for
cows that received dexamethasone only or dexamethasone plus insulin compared with
control and Ins received cows. There were no treatment effects on test-day milk
production, milk fat and protein percentages. CONCLUSIONS: The results suggested
that administration of glucocorticoids in early lactation resulted in short-term
improvement of metabolism in postpartum dairy cows in biochemical terms.
PMID- 26422372
TI - Social Support for First-Time Chinese Mothers in Contexts of Provider-Recipient
Relationships.
AB - This study examined the influence of social support on perceived stress and
online support activities in two relationship contexts. In 2013, we surveyed 366
first-time mothers between the ages of 26 and 30 years from mainland China about
their social support experiences with their mothers and mothers-in-law in regard
to child rearing. Women who received higher levels of support from their mothers
reported lower levels of perceived stress and higher levels of online support
activities. Receiving support from mothers-in-law was not associated with either
perceived stress or online support activities. The findings demonstrate the
importance of considering relationship contexts when examining social support
outcomes. Implications for future research on social support and interpersonal
relationships are discussed.
PMID- 26422373
TI - Co-delivery of Pirarubicin and Paclitaxel by Human Serum Albumin Nanoparticles to
Enhance Antitumor Effect and Reduce Systemic Toxicity in Breast Cancers.
AB - In our study, we aimed to develop a codelivery nanoparticulate system of
pirarubicin (THP) and paclitaxel (PTX) (Co-AN) using human serum albumin to
improve the therapeutic effect and reduce systemic toxicities. The prepared Co-AN
demonstrated a narrow size distribution around 156.9 +/- 3.2 nm (PDI = 0.16 +/-
0.02) and high loading efficiency (87.91 +/- 2.85% for THP and 80.20 +/- 2.21%
for PTX) with sustained release profiles. Significantly higher drug accumulation
in tumors and decreased distribution in normal tissues were observed for Co-AN in
xenograft 4T1 murine breast cancer bearing BALB/c mice. Cytotoxicity test against
4T1 cells in vitro and antitumor assay on 4T1 breast cancer in vivo demonstrated
that the antitumor effect of Co-AN was superior to that of the single drug or
free combination. Also, Co-AN induced increased apoptosis and G2/M cell cycle
arrest against 4T1 cells compared to that of the single drug formulation.
Remarkably, Co-AN exhibited significantly lower side effects regarding bone
marrow suppression and organ and gastrointestinal toxicities. This human serum
albumin-based codelivery system represents a promising platform for combination
chemotherapy in breast cancers.
PMID- 26422374
TI - Sequence Factorization with Multiple References.
AB - The success of high-throughput sequencing has lead to an increasing number of
projects which sequence large populations of a species. Storage and analysis of
sequence data is a key challenge in these projects, because of the sheer size of
the datasets. Compression is one simple technology to deal with this challenge.
Referential factorization and compression schemes, which store only the
differences between input sequence and a reference sequence, gained lots of
interest in this field. Highly-similar sequences, e.g., Human genomes, can be
compressed with a compression ratio of 1,000:1 and more, up to two orders of
magnitude better than with standard compression techniques. Recently, it was
shown that the compression against multiple references from the same species can
boost the compression ratio up to 4,000:1. However, a detailed analysis of using
multiple references is lacking, e.g., for main memory consumption and optimality.
In this paper, we describe one key technique for the referential compression
against multiple references: The factorization of sequences. Based on the notion
of an optimal factorization, we propose optimization heuristics and identify
parameter settings which greatly influence 1) the size of the factorization, 2)
the time for factorization, and 3) the required amount of main memory. We
evaluate a total of 30 setups with a varying number of references on data from
three different species. Our results show a wide range of factorization sizes
(optimal to an overhead of up to 300%), factorization speed (0.01 MB/s to more
than 600 MB/s), and main memory usage (few dozen MB to dozens of GB). Based on
our evaluation, we identify the best configurations for common use cases. Our
evaluation shows that multi-reference factorization is much better than single
reference factorization.
PMID- 26422375
TI - Assessment of Bacterial Community Assembly Patterns and Processes in Pig Manure
Slurry.
AB - The bacterial community assembly patterns and processes are poorly understood in
pig manure slurry. We collected pig manure slurry samples during the winter and
summer seasons from eight commercial pig farms in South Korea. The V3 region of
16S rRNA genes was PCR amplified and sequenced using paired-end Illumina
technology for in-depth characterization of bacterial community. Firmicutes,
Bacteroidetes, Proteobacteria, Spirochaetes, and Tenericutes were the predominant
bacterial phyla present in slurry samples. Bacterial taxonomic community
composition was not influenced by the season; however, phylogenetic community
composition was affected by seasonal variations. The community composition and
diversity patterns were strongly influenced by pH. The bacterial diversity
indices showed a unimodal relationship with pH. Phylogenetic signals were
detected over only short phylogenetic distances, revealing that closely related
bacterial operational taxonomic units (OTUs) tend to co-occur in the same
environment; hence, they are ecologically similar. Across all samples, a niche
based process, through strong environmental filtering imposed by pH, primarily
governed bacterial community assembly; however, in samples close to the neutral
pH range, the role of environmental filtering was decreased due to neutral
community assembly. In summary, pH emerged as the major physico-chemical variable
in pig manure slurry that regulates the relative importance of niche-based and
neutral processes in shaping the community assembly of bacteria.
PMID- 26422377
TI - Enhanced recovery: Minimally aggressive perioperative practice.
PMID- 26422376
TI - Gut Microbiome of an 11th Century A.D. Pre-Columbian Andean Mummy.
AB - The process of natural mummification is a rare and unique process from which
little is known about the resulting microbial community structure. In the present
study, we characterized the microbiome of paleofeces, and ascending, transverse
and descending colon of an 11th century A.D. pre-Columbian Andean mummy by 16S
rRNA gene high-throughput sequencing and metagenomics. Firmicutes were the most
abundant bacterial group, with Clostridium spp. comprising up to 96.2% of the
mummified gut, while Turicibacter spp. represented 89.2% of the bacteria
identified in the paleofeces. Microbiome profile of the paleofeces was unique
when compared to previously characterized coprolites that did not undergo natural
mummification. We identified DNA sequences homologous to Clostridium botulinum,
Trypanosoma cruzi and human papillomaviruses (HPVs). Unexpectedly, putative
antibiotic-resistance genes including beta-lactamases, penicillin-binding
proteins, resistance to fosfomycin, chloramphenicol, aminoglycosides, macrolides,
sulfa, quinolones, tetracycline and vancomycin, and multi-drug transporters, were
also identified. The presence of putative antibiotic-resistance genes suggests
that resistance may not necessarily be associated with a selective pressure of
antibiotics or contact with European cultures. Identification of pathogens and
antibiotic-resistance genes in ancient human specimens will aid in the
understanding of the evolution of pathogens as a way to treat and prevent
diseases caused by bacteria, microbial eukaryotes and viruses.
PMID- 26422379
TI - Validity of Self-Reported Psoriasis in a General Population: The HUNT Study,
Norway.
PMID- 26422380
TI - Desmoglein 3-Dependent Signaling Regulates Keratinocyte Migration and Wound
Healing.
AB - The desmosomal transmembrane adhesion molecules desmoglein 3 (Dsg3) and
desmocollin 3 (Dsc3) are required for strong keratinocyte cohesion. Recently, we
have shown that Dsg3 associates with p38MAPK and suppresses its activity. Here,
we further investigated the role of Dsg3-dependent control of p38MAPK function.
Dsg3-deficient mice display recurrent spontaneously healing skin erosions. In
lesional and perilesional biopsies, p38MAPK activation was detectable compared to
control animals. This led us to speculate that Dsg3 regulates wound repair in a
p38MAPK-dependent manner. Indeed, scratch wounded keratinocyte monolayers
exhibited p38MAPK activation and loss of Dsg3 in cells lining the wound edge.
Human keratinocytes after silencing of Dsg3 as well as primary cells isolated
from Dsg3 knockout animals exhibited accelerated migration, which was further
corroborated in an ex vivo skin outgrowth assay. Importantly, migration was
efficiently blocked by inhibition of p38MAPK, indicating that p38MAPK mediates
the effects observed upon loss of Dsg3. In line with this, we show that levels of
active p38MAPK associated with Dsc3 are increased in Dsg3-deficient cells. These
data indicate that Dsg3 controls a switch from an adhesive to a migratory
keratinocyte phenotype via p38MAPK inhibition. Thus, loss of Dsg3 adhesion may
foster wound closure by allowing p38MAPK-dependent migration.Journal of
Investigative Dermatology accepted article preview online, 30 September 2015.
doi:10.1038/jid.2015.380.
PMID- 26422378
TI - The GADD45A (1506T>C) Polymorphism Is Associated with Ovarian Cancer
Susceptibility and Prognosis.
AB - GADD45A (growth arrest and DNA damage 45 A) is the first stress-inducible gene
identified to be a target of p53. However, no studies to date have assessed
variants of the GADD45 gene and their potential relationship to tumor
susceptibility. We investigated the association of the GADD45A (1506T>C)
polymorphism with ovarian cancer development in 258 ovarian cancer patients and
332 age-matched healthy women as controls using sequence analysis. We found a
statistically significant difference in the GADD45A (1506T>C) genotype
distributions between the case and control groups (TT vs. TC vs. CC, P = 0.0021)
and found that variant 1506T>C was significantly associated with an increased
risk of ovarian cancer (P<0.001, OR = 1.71, 95% CI [1.28-2.29]). We observed a
statistically significant effect between tumor histology (P = 0.032) and CA125
status (P = 0.021). Carrying the C allele (TC+CC) was associated with an
increased risk of positive CA125 (OR = 3.20, 95% CI [1.15-8.71). Carrying the T
allele (TT+TC) showed a significant correlation with both higher GADD45A mRNA
expression and longer ovarian cancer RFS (relapse-free survival) and OS (overall
survival). We are the first group to demonstrate that the GADD45A (1506T>C)
polymorphism is associated with ovarian cancer susceptibility and prognosis.
These data suggest that GADD45A (1506T>C) is a new tumor susceptibility gene and
could be a useful molecular marker for assessing ovarian cancer risk and for
predicting ovarian cancer patient prognosis.
PMID- 26422381
TI - Immunomodulatory Activities of the Benzoxathiole Derivative BOT-4-One Ameliorate
Pathogenic Skin Inflammation in Mice.
AB - T cell-mediated immune responses play an important role in body protection.
However, aberrantly activated immune responses are responsible for inflammatory
and autoimmune diseases. The regulation of pathological immune responses may be a
potential therapeutic strategy for the treatment of these diseases. Despite
multiple pharmacological properties of benzoxathiole derivatives have been
defined, the molecular mechanisms underlying these properties remain to be
clarified. Here, we demonstrated the benzoxathiole derivative 2-cyclohexylimino-6
methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one) regulated immune
responses and ameliorated experimentally induced inflammatory skin diseases both
in vitro and in vivo. BOT-4-one inhibited the differentiation of CD4+ T-cell
subsets by regulating the expression and production of T cell lineage-specific
master transcription factors and cytokines and activating the signal transducer
and activator of transcription (STAT) proteins. In addition, BOT-4-one inhibited
T-cell receptor (TCR)-mediated Akt and nuclear factor-kappaB (NF-kappaB)
signaling. Topical application of BOT-4-one ameliorated experimentally induced
inflammatory skin diseases in mice models such as TNCB-induced contact and atopic
dermatitis and IL-23-induced psoriasis-like skin inflammation. Our study
demonstrated that BOT-4-one ameliorates inflammatory skin diseases by suppressing
the pathogenic CD4+ T cell differentiation and the overall immune
responses.Journal of Investigative Dermatology accepted article preview online,
30 September 2015. doi:10.1038/jid.2015.384.
PMID- 26422382
TI - Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of
Barrier-Deficient Mice with Reduced Cancer Susceptibility.
AB - Mice lacking three epidermal barrier proteins-envoplakin, periplakin and
involucrin-(EPI-/- mice) have a defective cornified layer, reduced epidermal
gammadelta T cells, increased dermal CD4+ T cells and are resistant to developing
skin tumours. The tumour-protective mechanism involves signalling between Rae-1
expressing keratinocytes and the Natural Killer Group 2D (NKG2D) receptor on
immune cells, which also plays a role in host defences against infection. Given
the emerging link between bacteria and cancer, we investigated whether EPI-/-
mice have an altered skin microbiota. The bacterial phyla were similar in wild
type and EPI-/- skin. However, bacteria were 3-fold more abundant in EPI-/- skin
and penetrated deeper into the epidermis. The major epithelial defense mechanism
against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin
exhibited enhanced expression of antimicrobial peptides. However, reducing the
bacterial load by antibiotic treatment or breeding mice under specific pathogen
free conditions did not reduce AMP expression or alleviate the abnormalities in T
cell populations. We conclude that the atopic characteristics of EPI-/- skin are
a consequence of the defective barrier rather than a response to the increased
bacterial load. It is therefore unlikely that the increase in skin microbiota
contributes directly to the observed cancer resistance.Journal of Investigative
Dermatology accepted article preview online, 30 September 2015.
doi:10.1038/jid.2015.383.
PMID- 26422383
TI - Spleen Tyrosine Kinase Mediates EGFR Signaling to Regulate Keratinocyte Terminal
Differentiation.
AB - Spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase, was initially
identified as a crucial regulator in proximal immunoreceptor signaling.
Additional studies have revealed its pleiotropic roles, and drugs targeting Syk
are under development for inflammatory diseases. Syk expression in the skin has
been detected, but its functions in the skin are still unknown. Here, we found
that Syk phosphorylation and expression in primary human keratinocytes decrease
gradually along with terminal differentiation. Human skin specimens showed
similar in vivo patterns. Syk inhibitors or knockdown of Syk increased the
expression of differentiation markers under in vitro differentiation models.
Furthermore, EGFR activation prominently induced Syk phosphorylation, which could
be inhibited by the EGFR inhibitor gefitinib or knockdown of EGFR. The Src
inhibitor also partially attenuated EGF-induced phosphorylation of Syk. However,
Syk inhibition suppressed EGF-induced phosphorylation of EGFR.
Immunoprecipitation and confocal microscopy further revealed the increased
molecular interaction between EGFR and Syk after EGF stimulation. This study
unravels the role of Syk in EGFR-mediated signaling and reveals regulatory roles
of Syk in keratinocyte differentiation, suggesting the clinical potential of
topical or systemic Syk inhibitors in the treatment of skin diseases with
aberrant differentiation.Journal of Investigative Dermatology accepted article
preview online, 30 September 2015. doi:10.1038/jid.2015.381.
PMID- 26422386
TI - In vitro Characterization of the Rapid Cytotoxicity of Anticancer Peptide HPRP-A2
through Membrane Destruction and Intracellular Mechanism against Gastric Cancer
Cell Lines.
AB - In this study, HPRP-A2, a synthetic 15-mer cationic peptides with all D-amino
acids, effectively inhibited the survival of gastric cell lines in a dose
dependent manner. Gastric tumor cells killing by HPRP-A2 involves a rapid
collapse of the membrane integrity and intracellular pathways. Propidium iodide
(PI) and lactate dehydrogenase (LDH) assays demonstrated that one-hour treatment
with HPRP-A2 led to membrane permeability changes of BGC-823 cells in a dose
dependent manner. Moreover, HPRP-A2 induced apoptosis in BGC-823 cells involves a
marked increase in generation of reactive oxygen species (ROS),caspase-3, -8 and
9 activation, a reduction of mitochondrial membrane potential (MMP), and cell
cycle arrest in G1 phase. In addition to its inherent cytotoxicity, HPRP-A2
synergized strongly with doxorubicin (DOX) to enhance the efficacy of killing
gastric tumor cells in vitro. We believe that HPRP-A2 with all D-amino acids
could be a potent candidate of anticancer therapeutics, especially in combination
therapy.
PMID- 26422387
TI - Spotting 2D atomic layers on aluminum nitride thin films.
AB - Substrates for 2D materials are important for tailoring their fundamental
properties and realizing device applications. Aluminum nitride (AIN) films on
silicon are promising large-area substrates for such devices in view of their
high surface phonon energies and reasonably large dielectric constants. In this
paper epitaxial layers of AlN on 2" Si wafers have been investigated as a
necessary first step to realize devices from exfoliated or transferred atomic
layers. Significant thickness dependent contrast enhancements are both predicted
and observed for monolayers of graphene and MoS2 on AlN films as compared to the
conventional SiO2 films on silicon, with calculated contrast values approaching
100% for graphene on AlN as compared to 8% for SiO2 at normal incidences.
Quantitative estimates of experimentally measured contrast using reflectance
spectroscopy show very good agreement with calculated values. Transistors of
monolayer graphene on AlN films are demonstrated, indicating the feasibility of
complete device fabrication on the identified layers.
PMID- 26422388
TI - Intragroup genetic relatedness in two howler monkey species (Alouatta pigra and
A. palliata): Implications for understanding social systems and dispersal.
AB - The degree of genetic relatedness among group members is influenced by dispersal,
group formation and composition, mating systems, and other socioecological
factors. Making inferences about differences between species in their socio
genetic structure is difficult because studies rarely compare multiple species.
In this study, we use multilocus microsatellite genotype data to analyze
intragroup genetic relatedness in two howler monkey species (Alouatta palliata
and A. pigra). We test the prediction that their patterns of intragroup genetic
relatedness will be distinct based on expectations derived from their distinct
social systems. Alouatta palliata is expected to have low levels of intragroup
relatedness, given that both males and females are reported to disperse from
their natal groups, and to join groups with no close kin. Levels of relatedness
among A. pigra group members are expected to be variable according to the history
of group formation, with new groups formed by unrelated individuals and well
established groups having close kin due to female nepotism and sometimes by
takeovers by coalitions of related males. Our results indicate that in both
species, most groups contain closely related same-sex and/or inter-sex dyads.
This suggests that philopatry in A. palliata may be more common than reported or
that individuals are using alternative strategies to reside with close kin. We
found greater variation among groups in female-female relatedness in A. palliata
than in A. pigra, implying that these species have distinct socio-genetic
structures. Further studies including both long-term observational and genetic
data are necessary to understand the mechanisms that determine the degree of
variation in intragroup genetic relatedness within and among populations for both
species. Ecological and demographic data are also necessary to determine the
importance of other factors, especially habitat loss and fragmentation, in
determining the degree of relatedness in howler monkey groups.
PMID- 26422390
TI - The Impact of Conservation Management on the Community Composition of Multiple
Organism Groups in Eutrophic Interconnected Man-Made Ponds.
AB - Ponds throughout the world are subjected to a variety of management measures for
purposes of biodiversity conservation. Current conservation efforts typically
comprise a combination of multiple measures that directly and indirectly impact a
wide range of organism groups. Knowledge of the relative impact of individual
measures on different taxonomic groups is important for the development of
effective conservation programs. We conducted a field study of 28 man-made ponds,
representing four management types differing in the frequency of periodic pond
drainage and the intensity of fish stock management. We disentangled the relative
importance of direct and indirect effects of pond management measures on the
community composition of phytoplankton, zooplankton, aquatic macro-invertebrates,
submerged and emergent vascular plants. With the exception of phytoplankton, pond
management had strong effects on the community composition of all investigated
biota. Whether management affected communities directly or indirectly through its
impact on fish communities or local environmental conditions in the pond varied
between organism groups. Overall, the impact of pond drainage regime and fish
community characteristics on the community composition of target organism groups
were more important than local environmental conditions. The majority of taxa
were negatively associated with fish density, whereas multiple emergent plant
species and several taxa of aquatic macro-invertebrates were positively affected
by increased drainage frequency. The effects of fish community and drainage
tended to be largely independent. The present study indicates that pond drainage
is an important element for biodiversity conservation in eutrophicated shallow
and interconnected man-made ponds.
PMID- 26422389
TI - High HER2 protein levels correlate with increased survival in breast cancer
patients treated with anti-HER2 therapy.
AB - INTRODUCTION: Current methods to determine HER2 (human epidermal growth factor
receptor 2) status are affected by reproducibility issues and do not reliably
predict benefit from anti-HER2 therapy. Quantitative measurement of HER2 may more
accurately identify breast cancer (BC) patients who will respond to anti-HER2
treatments. METHODS: Using selected reaction monitoring mass spectrometry (SRM
MS), we quantified HER2 protein levels in formalin-fixed, paraffin-embedded
(FFPE) tissue samples that had been classified as HER2 0, 1+, 2+ or 3+ by
immunohistochemistry (IHC). Receiver operator curve (ROC) analysis was conducted
to obtain optimal HER2 protein expression thresholds predictive of HER2 status
(by standard IHC or in situ hybridization [ISH]) and of survival benefit after
anti-HER2 therapy. RESULTS: Absolute HER2 amol/MUg levels were significantly
correlated with both HER2 IHC and amplification status by ISH (p < 0.0001). A
HER2 threshold of 740 amol/MUg showed an agreement rate of 94% with IHC and ISH
standard HER2 testing (p < 0.0001). Discordant cases (SRM-MS-negative/ISH
positive) showed a characteristic amplification pattern known as double minutes.
HER2 levels >2200 amol/MUg were significantly associated with longer disease-free
survival (DFS) and overall survival (OS) in an adjuvant setting and with longer
OS in a metastatic setting. CONCLUSION: Quantitative HER2 measurement by SRM-MS
is superior to IHC and ISH in predicting outcome after treatment with anti-HER2
therapy.
PMID- 26422391
TI - Candidate Loci are Revealed by an Initial Genome-wide Association Study of
Juvenile Osteochondritis Dissecans.
AB - BACKGROUND: Osteochondritis dissecans (OCD) is a condition that oftentimes causes
significant knee pain in pediatric patient populations. If left untreated, OCD
significantly increases the risk of developing degenerative osteoarthritis along
with its associated consequences and costs. Although a genetic component has been
suggested to play a role in this disorder, few studies have been carried out in
order to determine the underlying genetic etiology of this relatively common
complex trait. The goal of our study was to perform an initial genome-wide
association study (GWAS) to uncover candidate loci associated with the
pathogenesis of OCD. METHODS: Blood samples were acquired from 2 cohorts, aged 0
to 18 years old, consisting of 209 OCD cases and 1855 population-matched
controls. Agencourt Genfind DNA isolation technology was used to isolate high
quality DNA from each sample. Genotype data was then generated utilizing the
Illumina Infinium BeadChip array to examine single-nucleotide polymorphisms
(SNPs). RESULTS: In an initial GWAS analysis of our cohort, where a SNP was
excluded if the Hardy-Weinberg Equilibrium test P<0.0001, the minor allele
frequency<5%, and the genotyping call rate<90%, we obtained our first results for
OCD. Although there was no SNP strictly reaching the threshold for genome-wide
significance at this early stage, multiple SNPs (35) at several loci revealed
evidence of suggestive association with OCD (P<5.0*10). CONCLUSIONS: The results
from our preliminary study are encouraging. Herein we not only discuss the
relevance and applicability of GWAS in studying a genetic basis for OCD, but have
also identified top signals that may suggest loci involved in coordinated
expression as well as a transcription factor involved in development that may be
highly relevant to this trait. CLINICAL RELEVANCE: If genetic predispositions for
OCD are detected early enough in life, attempts at activity modification,
counseling, and orthopaedic monitoring may successfully reduce progression of
this condition, which may lead to progressive osteoarthritis in the third to
fourth decade in at-risk patients.
PMID- 26422392
TI - Successful Pavlik Harness Treatment for Developmental Dysplasia of the Hip and
Normal X-Ray at the Age of 2 Years: Is a Longer Follow-up Necessary?
AB - BACKGROUND: Management of developmental dysplasia of the hip (DDH) with a Pavlik
harness is a well-known treatment.Follow-up until skeletal maturity is
recommended as long-term studies mention late sequelae.The purpose of this study
was to determine whether such a follow-up is necessary in patients treated
successfully under a strict protocol. METHODS: A retrospective review of a
consecutive series of normal infants treated for DDH between January 1995 and
July 2004 was undertaken.Only normal infants with frankly pathologic hips treated
successfully with a Pavlik harness were included, and with a normal
anteroposterior (AP) pelvis x-ray at the age of 2 years.All infants with any type
of neurological disease, syndrome, other form of treatment for DDH, and failure
of the Pavlik harness were excluded.At the last follow-up, a clinical examination
and a standing AP pelvis x-ray were performed. RESULTS: A total of 109 hips in 83
children were available for review. The mean follow-up was of 10 years and 2
months. All 109 hips had a normal clinical examination and a normal AP pelvis x
ray: a mean center-edge angle (CEA) of 29.5 degrees, SD+/-4.1 degrees, a mean
acetabular index (AI) of 1457+/-3.74 degrees, a mean Sharp's angle of 41.92+/
3.42 degrees, a Seringe-Severin score of IA, a normal teardrop figure, no signs
of avascular necrosis, and Moses circles <2. CONCLUSION: This study strongly
suggests that in a selected group of patients treated for DDH with a Pavlik
harness, under a strict protocol, and a normal x-ray at 2 years of age, a long
term follow-up is not necessary. LEVEL OF EVIDENCE: Level III-therapeutic.
PMID- 26422393
TI - Spontaneous Fatal Intraoperative Rupture of Great Vessel During Growing Rod
Lengthening: Do Children With Ehlers-Danlos Syndrome Require the Availability of
Vascular Expertise? A Case Report and Review of the Literature.
AB - BACKGROUND: Ehlers-Danlos syndrome (EDS) is a family of inherited connective
tissue diseases. Kyphoscoliotic EDS (kEDS) is associated with severe and early
spinal deformity. Very little has been reported regarding the orthopaedic
surgical care of kEDS likely due to its rare incidence. A more common subtype is
the vascular-type EDS (vEDS, previously labeled type IV), which is associated
with reports of vascular complications in the literature. METHODS: The case
report of a single, fatal complication of spontaneous rupture of the superior
vena cava, after extubation, subsequent to revision minimal growing rod
lengthening in a child with kEDS. We additionally review prior reported cases of
kEDS for pediatric spine surgery and the sentinel event of spontaneous vascular
rupture in all EDS patients. RESULTS: The anterior thoracoabdominal approach in
children with kEDS has been associated with severe intravascular complications,
with no deaths reported to date. Posterior spinal procedures were associated with
frequent overall complications, but no events of perioperative or spontaneous
vascular injury were identified before our case.Reports of spontaneous vessel
rupture (n=39) appear more frequently in vEDS, but have been documented in
patients with EDS type I (classic EDS or cEDS) and kEDS disease. The 30-day
mortality in these patients was 59%. The majority of the deaths occurred on the
day of the vascular event. Surviving patients overwhelmingly received
intraoperative consultation and treatment from either general or vascular
surgeons at their respective institutions for assistance. CONCLUSIONS: Providers
should consider their proximity to available emergent consultation before
operating on patients with EDS of any subtype. LEVEL OF EVIDENCE: Level V-expert
opinion.
PMID- 26422394
TI - Bivalved Versus Circumferential Cast Immobilization for Displaced Forearm
Fractures: A Randomized Clinical Trial to Assess Efficacy and Safety.
AB - BACKGROUND: The purpose of this study was to determine the effects of bivalved
versus circumferential cast immobilization on maintenance of reduction and
associated complications after closed reduction (CR) of radius and/or ulna
fractures in children. METHODS: Two hundred two children with displaced radius
and/or ulna fractures were randomized to either circumferential (n=101) or
bivalved (n=101) long-arm casts after CR. The mean age was 10+/-3 years. There
were no significant differences between groups in terms of age, sex, or initial
fracture displacement or angulation. Clinical and radiographic evaluations were
performed at 1, 2, 4, and 6 weeks postreduction. Radiographic loss of reduction
(LOR), need for remanipulation or surgery, and associated complications of
compartment syndrome, cast saw injury, and neurovascular compromise were
recorded. RESULTS: Overall, the median angulation of the radius and ulna
fractures improved from 20 and 18 degrees to 3 and 2 degrees after CR,
respectively. The median cast index after reduction was 0.78 in the bivalved
group and 0.80 in the circumferential group. The median angulation of the radius
and ulna was 8 and 1 degrees at 4 weeks, with no significant difference between
groups. By the fourth week of follow-up, 70 patients (34%)-35 bivalved and 35
circumferential-had radiographic LOR. Forty-seven patients (23%)-23 bivalved and
24 circumferential-underwent remanipulation or surgical reduction and fixation.
There were no significant differences between groups with respect to LOR rate or
need for surgical treatment. One bivalved patient sustained a cast saw injury,
and 3 bivalved patients had transient neurological abnormalities. No patients
developed compartment syndrome. CONCLUSIONS: Cast immobilization is effective in
the majority of patients after CR of displaced forearm fractures. There were no
significant differences in maintenance of reduction, need for surgery, or
complications between bivalved or circumferential long-arm casts. LEVEL OF
EVIDENCE: Level I-therapeutic.
PMID- 26422395
TI - SIRT1 and insulin resistance.
AB - Sirtuin 1 (SIRT1) is a prototype mammalian NAD(+)-dependent protein deacetylase
that has emerged as a key metabolic sensor in various metabolic tissues. Growing
evidence suggests that SIRT1 regulates glucose and lipid metabolism through its
deacetylase activity. In this review, we have summarized the recent progress in
SIRT1 research with a particular focus on the role of SIRT1 in insulin resistance
at different metabolic tissues. Recent data indicate that activated SIRT1
improves the insulin sensitivity of liver, skeletal muscle and adipose tissues
and protects the function and cell mass of pancreatic beta-cells. These findings
suggest that SIRT1 might be a new therapeutic target for the prevention of
disease related to insulin resistance, such as metabolic syndrome and type 2
diabetes mellitus.
PMID- 26422396
TI - The relationship between carbohydrate and the mealtime insulin dose in type 1
diabetes.
AB - A primary focus of the nutritional management of type 1 diabetes has been on
matching prandial insulin therapy with carbohydrate amount consumed. Different
methods exist to quantify carbohydrate including counting in one gram increments,
10g portions or 15g exchanges. Clinicians have assumed that counting in one gram
increments is necessary to precisely dose insulin and optimize postprandial
control. Carbohydrate estimations in portions or exchanges have been thought of
as inadequate because they may result in less precise matching of insulin dose to
carbohydrate amount. However, studies examining the impact of errors in
carbohydrate quantification on postprandial glycemia challenge this commonly held
view. In addition it has been found that a single mealtime bolus of insulin can
cover a range of carbohydrate intake without deterioration in postprandial
control. Furthermore, limitations exist in the accuracy of the nutrition
information panel on a food label. This article reviews the relationship between
carbohydrate quantity and insulin dose, highlighting limitations in the evidence
for a linear association. These insights have significant implications for
patient education and mealtime insulin dose calculations.
PMID- 26422398
TI - A Case Report of Unresectable Cutaneous Squamous Cell Carcinoma Responsive to
Pembrolizumab, a Programmed Cell Death Protein 1 Inhibitor.
PMID- 26422397
TI - SATB1 Mediates Long-Range Chromatin Interactions: A Dual Regulator of Anti
Apoptotic BCL2 and Pro-Apoptotic NOXA Genes.
AB - Aberrant expression of special AT-rich binding protein 1 (SATB1), a global
genomic organizer, has been associated with various cancers, which raises the
question of how higher-order chromatin structure contributes to carcinogenesis.
Disruption of apoptosis is one of the hallmarks of cancer. We previously
demonstrated that SATB1 mediated specific long-range chromosomal interactions
between the mbr enhancer located within 3'-UTR of the BCL2 gene and the promoter
to regulate BCL2 expression during early apoptosis. In the present study, we used
chromosome conformation capture (3C) assays and molecular analyses to further
investigate the function of the SATB1-mediated higher-order chromatin structure
in co-regulation of the anti-apoptotic BCL2 gene and the pro-apoptotic NOXA gene
located 3.4Mb downstream on Chromosome 18. We demonstrated that the mbr enhancer
spatially juxtaposed the promoters of BCL2 and NOXA genes through SATB1-mediated
chromatin-loop in Jurkat cells. Decreased SATB1 levels switched the mbr-BCL2 loop
to mbr-NOXA loop, and thus changed expression of these two genes. The SATB1
mediated dynamic switch of the chromatin loop structures was essential for the
cooperative expression of the BCL2 and NOXA genes in apoptosis. Notably, the role
of SATB1 was specific, since inhibition of SATB1 degradation by caspase-6
inhibitor or caspase-6-resistant SATB1 mutant reversed expression of BCL-2 and
NOXA in response to apoptotic stimulation. This study reveals the critical role
of SATB1-organized higher-order chromatin structure in regulating the dynamic
equilibrium of apoptosis-controlling genes with antagonistic functions and
suggests that aberrant SATB1 expression might contribute to cancer development by
disrupting the co-regulated genes in apoptosis pathways.
PMID- 26422399
TI - Facile Preparation of Graphene/SnO2 Xerogel Hybrids as the Anode Material in Li
Ion Batteries.
AB - SnO2 has been considered as one of the most promising anode materials for Li-ion
batteries due to its theoretical ability to store up to 8.4 Li(+). However, it
suffers from poor rate performance and short cycle life due to the low intrinsic
electrical conductivity and particle pulverization caused by the large volume
change upon lithiation/delithiation. Here, we report a facile synthesis of
graphene/SnO2 xerogel hybrids as anode materials using epoxide-initiated gelation
method. The synthesized hybrid materials (19% graphene/SnO2 xerogel) exhibit
excellent electrochemical performance: high specific capacity, stable
cyclability, and good rate capability. Even cycled at a high current density of 1
A/g for 300 cycles, the hybrid electrode can still deliver a specific capacity of
about 380 mAh/g, corresponding to more than 60% capacity retention. The
incorporation of graphene sheets provides fast electron transfer between the
interfaces of the graphene nanosheets and the SnO2 and a short lithium ion
diffusion path. The porous structure of graphene/xerogel and the strong
interaction between SnO2 and graphene can effectively accommodate the volume
change and tightly confine the formed Li2O and Sn nanoparticles, thus preventing
the irreversible capacity degradation.
PMID- 26422400
TI - Update on nonsurgical lung volume reduction procedures.
PMID- 26422402
TI - Clinical outcomes associated with home mechanical ventilation: A systematic
review.
PMID- 26422401
TI - Investigation of occupational asthma: Do clinicians fail to identify relevant
occupational exposures?
AB - BACKGROUND: Specific inhalation challenges (SIC) enable the identification of the
agent responsible of occupational asthma (OA). A clinician may fail to identify a
specific agent in the workplace, which may potentially lead to a misdiagnosis.
The expert assessment method performed by an occupational hygienist has been used
to evaluate occupational exposures in epidemiological studies. OBJECTIVE: The
broad aim of the present study was to evaluate the contribution of an expert
assessment performed by an occupational hygienist to the diagnosis of OA. The
specific aim was to compare workplace exposures identified by an occupational
hygienist and by chest physicians in subjects with positive SICs and subjects
with asthma, but with a negative SIC. METHODS: SICs were performed in 120 cases:
67 were positive and 53 were negative. A clinician assessed occupational
exposures to sensitizers during a routine clinical evaluation preceding the
performance of the SIC. An expert assessment of occupational exposures was
performed by an occupational hygienist blind to the result of the SIC. RESULTS:
The occupational hygienist identified the causal agent in 96.7% of the 61 cases
of positive SIC. In 33 (62.3%) cases of negative SICs, the occupational hygienist
identified >=1 sensitizing agent(s) that had not been identified by the
clinician. CONCLUSION: The hygienist identified the causal agent in almost all
subjects with OA. In contrast, the clinician failed to identify potential
exposures to sensitizers in >60% of the negative SIC subjects, which may have
resulted in some subjects being misdiagnosed as not having OA.
PMID- 26422403
TI - MgtE From Rhizobium leguminosarum Is a Mg2+ Channel Essential for Growth at Low
pH and N2 Fixation on Specific Plants.
AB - MgtE is predicted to be a Rhizobium leguminosarum channel and is essential for
growth when both Mg2+ is limiting and the pH is low. N2was only fixed at 8% of
the rate of wild type when the crop legume Pisum sativum was inoculated with an
mgtE mutant of R. leguminosarum and, although bacteroids were present, they were
few in number and not fully developed. R. leguminosarum MgtE was also essential
for N2fixation on the native legume Vicia hirsuta but not when in symbiosis with
Vicia faba. The importance of MgtE and the relevance of the contrasting
phenotypes is discussed.
PMID- 26422404
TI - Sinorhizobium meliloti Controls Nitric Oxide-Mediated Post-Translational
Modification of a Medicago truncatula Nodule Protein.
AB - Nitric oxide (NO) is involved in various plant-microbe interactions. In the
symbiosis between soil bacterium Sinorhizobium meliloti and model legume Medicago
truncatula, NO is required for an optimal establishment of the interaction but is
also a signal for nodule senescence. Little is known about the molecular
mechanisms responsible for NO effects in the legume-rhizobium interaction. Here,
we investigate the contribution of the bacterial NO response to the modulation of
a plant protein post-translational modification in nitrogen-fixing nodules. We
made use of different bacterial mutants to finely modulate NO levels inside M.
truncatula root nodules and to examine the consequence on tyrosine nitration of
the plant glutamine synthetase, a protein responsible for assimilation of the
ammonia released by nitrogen fixation. Our results reveal that S. meliloti
possesses several proteins that limit inactivation of plant enzyme activity via
NO-mediated post-translational modifications. This is the first demonstration
that rhizobia can impact the course of nitrogen fixation by modulating the
activity of a plant protein.
PMID- 26422405
TI - Effects of Elevated CO2and Temperature on Pathogenicity Determinants and
Virulence of Potato virus X/Potyvirus-Associated Synergism.
AB - Infections of plants by multiple viruses are common in nature and may result in
synergisms in pathologies. Several environmental factors influence plant-virus
interactions and act on virulence and host defense responses. Mixed viral
infections may be more frequent under environmental conditions associated with
global warming. Here, we address how changes in the two main parameters behind
global warming, carbon dioxide concentrations ([CO2]) and temperature, may affect
virulence of Potato virus X (PVX)/potyvirus-associated synergism compared with
single infections in Nicotiana benthamiana. Elevated [CO2] resulted in attenuated
virulence of single infection by PVX, which correlated with a lower accumulation
of virus. In contrast, virulence of PVX/potyvirus-associated synergism was
maintained at elevated [CO2]. On the other hand, elevated temperature decreased
markedly both virulence and virus titers in the synergistic infection. We also
show that the HR-like response elicited by transient coexpression of PVX P25
together with the potyviral helper component-proteinase protein was significantly
enhanced by elevated temperature, whereas it was reduced by elevated [CO2]. Both
proteins are main pathogenicity determinants in PVX-associated synergisms. These
findings indicate that, under environmental conditions associated with global
warming, virulence of PVX/potyvirus-associated synergisms is expected to vary
relative to single infections and, thus, may have pathological consequences in
the future.
PMID- 26422406
TI - Changes in Upper Airway Volume in Edentulous Obstructive Sleep Apnea Patients
Treated with Modified Mandibular Advancement Device.
AB - PURPOSE: This study was an attempt to verify the utility of complete dentures
modified as a mandibular advancement device (MAD) in effecting expansion in
pharyngeal volume to treat obstructive sleep apnea (OSA) in edentulous patients.
MATERIALS AND METHODS: The sample consisted of 17 patients (12 male, 5 female,
average age 61 +/- 4 years; BMI, 22 +/- 5; apnea hypopnea index [AHI] 15 to 30).
All patients had worn complete dentures for at least 1 year; all patients had the
dentures modified to a MAD. Five variables were assessed preoperatively and 6
months after wearing the modified MADs. These variables were: sleep efficiency,
AHI, oxygen desaturation events/hr., mean oxygen saturation, snoring index, and
airway volume. This assessment was done by subjecting the patients to all-night
polysomnography. RESULTS: Without any prosthesis or device in the edentulous
patients, the mean velopharyngeal volume was 8.05 +/- 0.58 cm(3) , oropharyngeal
volume was 2.14 +/- 0.38 cm(3) , and hypopharyngeal volume was 3.26 +/- 0.78
cm(3) . With complete dentures (unaltered) in the edentulous patients, the mean
velopharyngeal, oropharyngeal, and hypopharyngeal volumes were 10.73 +/- 0.98
cm(3) , 2.60 +/- 0.48 cm(3) , and 4.31 +/- 0.89 cm(3) , respectively. There was a
statistically significant change in the airway volume following insertion of the
complete dentures modified as MADs with velopharyngeal, oropharyngeal, and
hypopharyngeal volume recorded as 11.76 +/- 1.07 cm(3) , 3.33 +/- 0.51 cm(3) ,
and 4.94 +/- 0.83 cm(3) , respectively. CONCLUSION: From the results obtained in
this limited small sample study, it was inferred that the pharyngeal expansion
induced by complete dentures modified as MADs effectively reduced symptoms of
OSA. Increased volume was most pronounced in the velopharynx region followed by
hypopharynx and oropharynx.
PMID- 26422407
TI - Serological survey of Bartonella spp., Borrelia burgdorferi, Brucella spp.,
Coxiella burnetii, Francisella tularensis, Leptospira spp., Echinococcus, Hanta-,
TBE- and XMR-virus infection in employees of two forestry enterprises in North
Rhine-Westphalia, Germany, 2011-2013.
AB - We initiated a survey to collect basic data on the frequency and regional
distribution of various zoonoses in 722 employees of forestry enterprises in the
German state of North Rhine-Westphalia (NRW) from 2011 to 2013. Exposures
associated with seropositivity were identified to give insight into the possible
risk factors for infection with each pathogen. 41.2% of participants were found
to be seropositive for anti-Bartonella IgG, 30.6% for anti-Borrelia burgdorferi
IgG, 14.2% for anti-Leptospira IgG, 6.5% for anti-Coxiella burnetii IgG, 6.0% for
anti-Hantavirus IgG, 4.0% for anti-Francisella tularensis IgG, 3.4% for anti-TBE
virus IgG, 1.7% for anti-Echinococcus IgG, 0.0% for anti-Brucella IgG and anti
XMRV IgG. Participants seropositive for B. burgdorferi were 3.96 times more
likely to be professional forestry workers (univariable analysis: OR 3.96; 95% CI
2.60-6.04; p<0.001); and participants seropositive for Hantavirus 3.72 times more
likely (univariable analysis: OR 3.72; 95% CI 1.44-9.57; p=0.007). This study
found a surprisingly high percentage of participants seropositive for anti-B.
henselae IgG and for anti-F. tularensis IgG. The relatively high seroprevalence
for anti-Leptospira IgG seen in this study could be related to living conditions
rather than to exposure at work. No specific risk for exposure to C. burnetii and
Echinococcus was identified, indicating that neither forestry workers nor office
workers represent a risk population and that NRW is not a typical endemic area.
Forestry workers appear to have higher risk for contact with B. burgdorferi
infected ticks and a regionally diverse risk for acquiring Hantavirus-infection.
The regional epidemiology of zoonoses is without question of great importance for
public health. Knowledge of the regional risk factors facilitates the development
of efficient prevention strategies and the implementation of such prevention
measures in a sustainable manner.
PMID- 26422408
TI - Lymph nodes can accurately be measured on PET-CT for lymphoma staging/restaging
without a concomitant contrast enhanced CT scan.
AB - Dual imaging with both contrast enhanced CT scan and PET-CT is recommended for
evaluation of lymphoma. We compared the performance in identification and size
measurements of involved lymph nodes in FDG-avid lymphomas on the low dose non
contrast enhanced CT of a PET-CT scan with those on a diagnostic contrast
enhanced CT scan. The size of FDG-avid lymph nodes was measured in both the short
and long axis on both the low dose non-contrast CT of the PET-CT and the contrast
enhanced CT by two independent readers. A total of 307 FGD avid lymph nodes were
identified in 52 patients. There was no statistically significant differences in
the measured size of the nodes on the non-contrast and contrast enhanced scans
(p=0.21). Baseline staging and restaging of FDG-avid lymphomas can be performed
with one test, PET-CT, without an accompanying contrast enhanced CT scan, with no
effect on the measured nodal size.
PMID- 26422409
TI - Reassessing the Efficiency Penalty from Carbon Capture in Coal-Fired Power
Plants.
AB - This paper examines thermal efficiency penalties and greenhouse gas as well as
other pollutant emissions associated with pulverized coal (PC) power plants
equipped with postcombustion CO2 capture for carbon sequestration. We find that,
depending on the source of heat used to meet the steam requirements in the
capture unit, retrofitting a PC power plant that maintains its gross power output
(compared to a PC power plant without a capture unit) can cause a drop in plant
thermal efficiency of 11.3-22.9%-points. This estimate for efficiency penalty is
significantly higher than literature values and corresponds to an increase of
about 5.3-7.7 USc/kWh in the levelized cost of electricity (COE) over the 8.4
USc/kWh COE value for PC plants without CO2 capture. The results follow from the
inclusion of mass and energy feedbacks in PC power plants with CO2 capture into
previous analyses, as well as including potential quality considerations for safe
and reliable transportation and sequestration of CO2. We conclude that PC power
plants with CO2 capture are likely to remain less competitive than natural gas
combined cycle (without CO2 capture) and on-shore wind power plants, both from a
levelized and marginal COE point of view.
PMID- 26422411
TI - NMR-based investigation of the Drosophila melanogaster metabolome under the
influence of daily cycles of light and temperature.
AB - We utilized an NMR-based metabolomic approach to profile the metabolites in
Drosophila melanogaster that cycle with a daily rhythm. 1H 1D and 2D NMR
experiments were performed on whole-body extracts sampled from flies that
experienced strong time cues in the form of both light and temperature cycles.
Multivariate and univariate statistical analysis was used to identify those
metabolites whose concentrations oscillate diurnally. We compared metabolite
levels at two time points twelve hours apart, one close to the end of the day and
the other close to the end of the night, and identified metabolites that differed
significantly in their relative concentrations. We were able to identify 14 such
metabolites whose concentrations differed significantly between the two time
points. The concentrations of metabolites such as sterols, fatty acids, amino
acids such as leucine, valine, isoleucine, alanine and lysine as well as other
metabolites such as creatine, glucose, AMP and NAD were higher close to the end
of the night, whereas the levels of lactic acid, and a few amino acids such as
histidine and tryptophan were higher close to the end of the day. We compared
signal intensities across 12 equally spaced time points for these 14 metabolites,
in order to profile the changes in their levels across the day, since the NMR
metabolite peak intensity is directly proportional to its molar concentration.
Through this report we establish NMR-based metabolomics combined with
multivariate statistical analysis as a useful method for future studies on the
interactions between circadian clocks and metabolic processes.
PMID- 26422412
TI - Simultaneous Occurrence of Pancreatic Adenocarcinoma and Brunner's Gland Adenoma
in a Siberian Tiger (Panthera tigris altaica).
AB - We describe a case of pancreatic adenocarcinoma and Brunner's gland adenoma in an
18-year-old male Siberian tiger (Panthera tigris altaica) from the Ljubljana Zoo.
The tiger was humanely destroyed due to weakness and progressive weight loss.
Necropsy examination revealed a large, grey, predominantly necrotic mass
replacing the major part of the pancreatic body. Microscopically, the mass was
unencapsulated, poorly demarcated, highly cellular and composed of highly
pleomorphic, cuboidal to tall columnar cells with basal, round or oval,
moderately anisokaryotic nuclei with prominent nucleoli and moderate to large
amounts of eosinophilic cytoplasm. The tumour was diagnosed as pancreatic tubular
adenocarcinoma with infiltration into the duodenum and mesentery. There were
tumour emboli in mesenteric blood vessels and hepatic metastases. The non
affected part of the pancreas exhibited severe chronic pancreatitis. In addition,
one firm white neoplastic nodule was observed in the duodenal wall. The nodule
was set in the tunica muscularis and was unencapsulated, well demarcated and
highly cellular, and consisted of a closely packed layer of normal Brunner's
glands and a centrally positioned group of irregularly branched tubules with
small amounts of debris in the lumen. The neoplastic nodule was diagnosed as
Brunner's gland adenoma. The present case is, to the best of our knowledge, the
first report of concurrent pancreatic adenocarcinoma and Brunner's gland adenoma,
most probably induced by chronic pancreatitis, either in man or animals.
PMID- 26422413
TI - Disease Risk Assessments Involving Companion Animals: an Overview for 15 Selected
Pathogens Taking a European Perspective.
AB - Prioritization of companion animal transmissible diseases was performed by the
Companion Animals multisectoriaL interprofessionaL Interdisciplinary Strategic
Think tank On zoonoses (CALLISTO) project. The project considered diseases
occurring in domesticated species commonly kept as pets, such as dogs and cats,
but also included diseases occurring in captive wild animals and production
animal species. The prioritization process led to the selection of 15 diseases of
prime public health relevance, agricultural economic importance, or both. An
analysis was made of the current knowledge on the risk of occurrence and
transmission of these diseases among companion animals, and from companion
animals to man (zoonoses) or to livestock. The literature was scanned for risk
assessments for these diseases. Studies were classified as import risk
assessments (IRAs) or risk factor analyses (RFAs) in endemic areas. For those
pathogens that are absent from Europe, only IRAs were considered; for pathogens
present throughout Europe, only RFAs were considered. IRAs were identified for
seven of the eight diseases totally or partially absent from Europe. IRAs for
classical rabies and alveolar echinococcosis found an increased risk for
introduction of the pathogen into officially disease-free areas as a consequence
of abandoning national rules and adopting the harmonized EU rules for pet travel.
IRAs for leishmaniosis focused on risk associated with the presence of
persistently infected dogs in new geographical areas, taking into consideration
the risk of disease establishment should a competent vector arise. IRAs for
Crimean-Congo haemorrhagic fever and West Nile fever indicated that the
likelihood of introduction via companion animals was low. IRAs for bluetongue
paid no attention to the risk of introduction via companion animals, which was
also the case for IRAs for foot-and-mouth disease, the only disease considered to
be absent from Europe. RFAs dealing with the risk factors for companion animals
to become infected were identified for eight of the 14 diseases found in Europe
or parts of it. RFAs for leptospirosis were most numerous (four studies). The
host related risk factor 'age' was identified as significant for dogs in at least
two RFAs for cystic echinococcosis and giardiasis. Among husbandry and healthcare
related factors, 'eating (uncooked) offal', 'being free roaming' and 'poor
deworming practice' were associated with risk for dogs in at least two RFAs for
cystic echinococcosis, while 'having received recent veterinary treatment' was
identified as a risk factor in at least two studies on infection with extended
spectrum beta lactamase-producing bacteria, one in horses and the other in dogs
and cats. Finally, although the environmental factors 'season' and 'hydrological
density' were identified as significant risk factors for dogs in at least two
RFAs for leptospirosis, the inconsistent case definitions used in those studies
made comparison of study results problematic. RFAs considering the risk of people
becoming infected from companion animals were identified for eight of the 14
diseases found in Europe or parts of it. RFAs for human campylobacteriosis were
the most numerous (n = 6). Most studies made an assessment as to whether keeping
a pet per se, or keeping a pet with supposed or known risk factors, was a risk
factor for people relative to other risks. This allowed some studies to report
the population attributable risk or population attributable fraction of the
incidence of human disease due to companion animals (for campylobacteriosis,
salmonellosis and toxoplasmosis), which is a measure that is easy to perceive for
laymen and policy makers. No RFAs were found that dealt with the risk to food
animals from companion animals for any of the 15 pathogens investigated. Few risk
method-based studies were identified that provided information on risk factors
for companion animals and on their role as a source of these 15 selected
diseases, indicating a clear knowledge gap. There were not enough assessments for
any of the 15 diseases to allow meta-analyses, whether these assessments dealt
with companion animal disease risk or companion animal-associated human disease
risk. Important method and technology gaps were the lack of harmonization in the
case definitions used for a given disease and the lack of good diagnostics
allowing pathogen identification to taxonomic levels that are meaningful for risk
analysis. Molecular epidemiology studies on zoonotic pathogens, which included
companion animals among the potential human risk factors, were not found,
although such studies would provide good preliminary insights without requiring
any tracing of people or any interviews. In addition to performing further risk
studies that take into account these issues, there is a need for responsible pet
ownership and continued education of professionals in companion animal zoonoses.
Additional risk assessment studies should allow more targeted actions to reduce
the risk of zoonotic diseases transferred via companion animals and provide
information that will promote risk-awareness in healthy human-animal
relationships.
PMID- 26422414
TI - Swiss Feline Cancer Registry: A Retrospective Study of the Occurrence of Tumours
in Cats in Switzerland from 1965 to 2008.
AB - Cancer is one of the leading causes of death in companion animals. Information on
the epidemiology of cancer is instrumental for veterinary practitioners in
patient management; however, spontaneously arising tumours in companion animals
also resemble those in man and can provide useful data in combating cancer.
Veterinary cancer registries for cats are few in number and have often remained
short-lived. This paper presents a retrospective study of tumours in cats in
Switzerland from 1965 to 2008. Tumour diagnoses were coded according to
topographical and morphological keys of the International Classification of
Oncology for Humans (ICD-O-3). Correlations between breed, sex and age were then
examined using a multiple logistic regression model. A total of 18,375 tumours
were diagnosed in 51,322 cats. Of these, 14,759 (80.3%) tumours were malignant.
Several breeds had significantly lower odds ratios for developing a tumour
compared with European shorthair cats. The odds of a cat developing a tumour
increased with age, up to the age of 16 years, and female cats had higher risk of
developing a tumour compared with male cats. Skin (4,970; 27.05%) was the most
frequent location for tumours, followed by connective tissue (3,498; 19.04%),
unknown location (2,532; 13.78%) and female sexual organs (1,564; 8.51%). The
most common tumour types were epithelial tumours (7,913; 43.06%), mesenchymal
tumours (5,142; 27.98%) and lymphoid tumours (3,911; 21.28%).
PMID- 26422416
TI - Can Contrast-Enhanced Multi-Detector Computed Tomography Replace Transesophageal
Echocardiography for the Detection of Thrombogenic Milieu and Thrombi in the Left
Atrial Appendage: A Prospective Study with 124 Patients.
AB - PURPOSE: To assess the diagnostic value of contrast-enhanced multi-detector
computed tomography (MD-CT) for identifying patients with left atrial appendage
(LAA) thrombus or circulatory stasis. MATERIALS AND METHODS: 124 patients with a
history of atrial fibrillation and/or cerebral ischemia (83 men, mean age 58.6 +/
12.4 years) and with a clinical indication for MD-CT of the heart and for
transesophageal echocardiography (TEE) were included in the study. LAA thrombus
or thrombogenic milieu was visually identified in TEE and MD-CT. In addition, MD
CT was analyzed quantitatively measuring the Hounsfield units (HU) of the left
atrium (LA), the LAA and the ascending aorta (AA), and calculating the HU ratios
LAA/AA (HU [LAA/AA]) und LAA/LA (HU [LAA/LA]). Sensitivity, specificity, negative
predictive value (NPV) and positive predictive value (PPV) were calculated.
RESULTS: The prevalence of a thrombus or thrombogenic milieu as assessed by TEE
was 21.8 %. The HU ratio was lower in patients with thrombus or thrombogenic
milieu (HU [LAA/AA]: 0.590 +/- 0.248 vs. 0.909 +/- 0.141; p < 0.001 und HU
[LAA/LA] 0.689 +/- 0.366 vs. 1.082 +/- 0.228; p < 0.001). For the diagnosis of
thrombus or a thrombogenic milieu, visual analysis yielded a sensitivity of 81.5
%, a specificity of 96.9 %, a PPV of 87.5 % and a NPV of 95.2 %. By combining
visual and quantitative analysis with one criterion being positive, the
specificity decreased to 91.8 %, the sensitivity to 77.8 %, the PPV to 72.4 %,
and the NPV to 94.9 %. CONCLUSION: Visual analysis of the LAA in the evaluation
of thrombus or thrombogenic milieu yields a high NPV of 95.1 % and may especially
be useful to rule out LAA thrombi in patients with contraindications for TEE.
Additional calculation of HU ratios did not improve the diagnostic performance of
MD-CT. KEY POINTS: * MD-CT can reliably exclude atrial appendage
thrombi/thrombogenic milieu. * MD-CT is an alternative method in patients with
contraindications to TEE. * Calculation of relative HU ratios does not improve
the diagnostic value of MD-CT.
PMID- 26422415
TI - Racial differences in adherence and response to combined treatment for full and
subthreshold post-traumatic stress disorder and alcohol use disorders: A
secondary analysis.
AB - We conducted a secondary data analysis to examine whether there were racial
differences in adherence and treatment outcomes for participants with co
occurring full and subthreshold post-traumatic stress disorder (PTSD) and
alcohol/substance use disorders (A/SUD) who were treated with Seeking Safety (a
cognitive-behavioral therapy) and sertraline or Seeking Safety and placebo as
part of a clinical trial. Bivarate analyses examined the association between race
and adherence, and generalized estimating equations assessed whether race
moderated the effect of combination treatment on PTSD and alcohol use outcomes.
Except for education, there were no statistically significant racial differences
in baseline demographic and psychiatric characteristics. African Americans and
Caucasians were equally adherent in number of psychotherapy and medication
sessions attended and medication compliance. After controlling for baseline
demographics and psychiatric symptoms, however, a race by treatment condition
interaction emerged suggesting that African Americans who received the Seeking
Safety and sertraline treatment had significantly lower PTSD symptom severity
posttreatment and at six months follow-up compared to their counterparts who
received Seeking Safety and placebo. No differential effect of treatment
condition was found for Caucasians. Moreover, results indicated that a diagnosis
of major depressive disorder negatively impacted PTSD symptom recovery for
African American participants but not for Caucasians. In conclusion, no
differences emerged between African Americans and Caucasians in adherence to
combination treatments for PTSD and A/SUD. Findings also suggest assessment and
treatment of MDD among African Americans may improve treatment outcomes. More
research is needed to determine whether the differential response to Seeking
Safety and sertraline among African Americans compared to Caucasians can be
replicated.
PMID- 26422417
TI - Implementation of Dose Monitoring Software in the Clinical Routine: First
Experiences.
AB - PURPOSE: Radiation exposure of the public as a result of medical imaging has
significantly increased during the last decades. To have a tool to register and
control patient dose exposure, we implemented dose monitoring software at our
institution and first connected our computed tomography (CT) scanners. MATERIALS
AND METHODS: CT dose data from July 2014 to February 2015 was retrospectively
analyzed using dose monitoring software. We evaluated a number of scans above
predefined dose thresholds ("alerts"), assessed reasons for alerts and compared
data of two CT scanners, one located close to the emergency room ("emergency CT
scanner") and one mainly used on an outpatient basis ("clinical routine CT
scanner"). To check for statistically significant differences between scanners,
chi-square-tests were performed. RESULTS: A total of 8883 scans were acquired
(clinical routine CT scanner, n = 3415; emergency CT scanner, n = 5468) during
which 316 alerts were encountered (alert quota, 4 %). The overall alert quota
ranged from 2 - 5 % with significantly higher values for the clinical routine CT
scanner. Reasons for alerts were high BMI (51 %), patient off-centering (24 %),
scan repetition (11 %), orthopedic hardware (9 %), or other (5 %). Scan
repetition was necessary significantly more often with the emergency CT scanner
(p = 0.019), while high BMI, off-centering and orthopedic hardware were more
frequently seen with the clinical routine CT scanner (for all, p < 0.05). There
was a good correlation between high body weight and dose above threshold (r =
0.585). CONCLUSION: Implementation of dose monitoring software in the clinical
routine was successfully accomplished and provides important information
regarding patient radiation protection. KEY POINTS: ? Implementation of dose
monitoring software in the clinical routine can be successfully accomplished. .
Dose notifications are due to human error or patient-specific factors. . Dose
monitoring software provides important information regarding radiation protection
of patients.
PMID- 26422418
TI - Texture-Based Analysis of 100 MR Examinations of Head and Neck Tumors - Is It
Possible to Discriminate Between Benign and Malignant Masses in a Multicenter
Trial?
AB - AIM: To evaluate whether texture-based analysis of standard MRI sequences can
help in the discrimination between benign and malignant head and neck tumors.
MATERIALS AND METHODS: The MR images of 100 patients with a histologically
clarified head or neck mass, from two different institutions, were analyzed.
Texture-based analysis was performed using texture analysis software, with region
of interest measurements for 2 D and 3 D evaluation independently for all axial
sequences. COC, RUN, GRA, ARM, and WAV features were calculated for all ROIs. 10
texture feature subsets were used for a linear discriminant analysis, in
combination with k-nearest-neighbor classification. Benign and malignant tumors
were compared with regard to texture-based values. RESULTS: There were
differences in the images from different field-strength scanners, as well as from
different vendors. For the differentiation of benign and malignant tumors, we
found differences on STIR and T2-weighted images for 2 D, and on contrast
enhanced T1-TSE with fat saturation for 3 D evaluation. In a separate analysis of
the subgroups 1.5 and 3 Tesla, more discriminating features were found.
CONCLUSION: Texture-based analysis is a useful tool in the discrimination of
benign and malignant tumors when performed on one scanner with the same protocol.
We cannot recommend this technique for the use of multicenter studies with
clinical data. KEY POINTS: 2 D/3 D texture-based analysis can be performed in
head and neck tumors. Texture-based analysis can differentiate between benign and
malignant masses. Analyzed MR images should originate from one scanner with an
identical protocol.
PMID- 26422419
TI - [Not Available].
PMID- 26422420
TI - [Ectopic ductus Bellini carcinoma of the adrenal gland: a rare differential
malignant adrenal gland tumors diagnosis].
PMID- 26422421
TI - Learning to decode human emotions with Echo State Networks.
AB - The aim of this paper is to identify the common neural signatures based on which
the positive and negative valence of human emotions across multiple subjects can
be reliably discriminated. The brain activity is observed via Event Related
Potentials (ERPs). ERPs are transient components in the Electroencephalography
(EEG) generated in response to a stimulus. ERPs were collected while subjects
were viewing images with positive or negative emotional content. Building inter
subject discrimination models is a challenging problem due to the high ERPs
variability between individuals. We propose to solve this problem with the aid of
the Echo State Networks (ESN) as a general framework for extracting the most
relevant discriminative features between multiple subjects. The original feature
vector is mapped into the reservoir feature space defined by the number of the
reservoir equilibrium states. The dominant features are extracted iteratively
from low dimensional combinations of reservoir states. The relevance of the new
feature space was validated by experiments with standard supervised and
unsupervised machine learning techniques. From one side this proof of concept
application enhances the usability context of the reservoir computing for high
dimensional static data representations by low-dimensional feature transformation
as functions of the reservoir states. From other side, the proposed solution for
emotion valence detection across subjects is suitable for brain studies as a
complement to statistical methods. This problem is important because such
decision making systems constitute "virtual sensors" of hidden emotional states,
which are useful in psychology science research and clinical applications.
PMID- 26422422
TI - Neuromorphic implementations of neurobiological learning algorithms for spiking
neural networks.
AB - The application of biologically inspired methods in design and control has a long
tradition in robotics. Unlike previous approaches in this direction, the emerging
field of neurorobotics not only mimics biological mechanisms at a relatively high
level of abstraction but employs highly realistic simulations of actual
biological nervous systems. Even today, carrying out these simulations
efficiently at appropriate timescales is challenging. Neuromorphic chip designs
specially tailored to this task therefore offer an interesting perspective for
neurorobotics. Unlike Von Neumann CPUs, these chips cannot be simply programmed
with a standard programming language. Like real brains, their functionality is
determined by the structure of neural connectivity and synaptic efficacies.
Enabling higher cognitive functions for neurorobotics consequently requires the
application of neurobiological learning algorithms to adjust synaptic weights in
a biologically plausible way. In this paper, we therefore investigate how to
program neuromorphic chips by means of learning. First, we provide an overview
over selected neuromorphic chip designs and analyze them in terms of neural
computation, communication systems and software infrastructure. On the
theoretical side, we review neurobiological learning techniques. Based on this
overview, we then examine on-die implementations of these learning algorithms on
the considered neuromorphic chips. A final discussion puts the findings of this
work into context and highlights how neuromorphic hardware can potentially
advance the field of autonomous robot systems. The paper thus gives an in-depth
overview of neuromorphic implementations of basic mechanisms of synaptic
plasticity which are required to realize advanced cognitive capabilities with
spiking neural networks.
PMID- 26422423
TI - Circadian Kisspeptin expression in human term placenta.
AB - Kisspeptin is an essential gatekeeper of reproductive function. During pregnancy
high circulating levels of kisspeptin have been described, however the clear role
of this neuropeptide in pregnancy remains unknown. We tested the existence of
rhythmic kisspeptin expression in human full-term placenta from healthy pregnant
women at six different time points during the day. The data obtained by Western
blotting were fitted to a mathematical model (Fourier series), demonstrating, for
the first time, the existence of a circadian rhythm in placental kisspeptin
expression.
PMID- 26422424
TI - Chemotherapy-Related Reticulate Hyperpigmentation: A Case Series and Review of
the Literature.
AB - BACKGROUND: Inherited or acquired reticulate hyperpigmentation represents a
heterogeneous group of infrequent dermatological conditions. The development of
reticulate hyperpigmentation has so far been rarely reported to be associated
with chemotherapeutic agents, including fluorouracil, bleomycin or a combination
of cytarabine and idarubicin. CASE REPORTS: We describe 5 cases of chemotherapy
related reticulate hyperpigmentation in patients treated with different
chemotherapeutic regimens, in particular paclitaxel or cytarabine. The lesions
were similar in all cases, with reticulate and/or linear hyperpigmented streaks,
which were mainly located to the back and buttocks. Histology showed increased
melanogenesis, which suggests a direct toxic effect of chemotherapy on
melanocytes. Reflectance confocal microscopy was performed in 2 patients showing
a similar pattern, with an increased amount of melanin in basal keratinocytes.
These features have been compared with the available data through a literature
review. CONCLUSION: Reticulate hyperpigmentation is an underestimated but
characteristic complication of chemotherapy. Neither specific management nor
discontinuation of the chemotherapeutic regimen is required.
PMID- 26422425
TI - Obesity: a key component of psoriasis.
AB - Psoriasis has been associated with several cardiometabolic comorbidities as well
as clinically significant increased risk of cardiovascular disease and mortality.
Obesity seems to have a key role in linking psoriasis and cardiovascular disease.
There are a growing number of epidemiological studies associating psoriasis and
obesity. The mechanism responsible for this association is not certain, but it is
probably multifactorial, involving genetic, environmental and immune-mediated
factors. Nonetheless, the chronic inflammatory state associated with obesity
appears to be a key component of this relationship. Obesity is, therefore, a
major factor in the management of psoriatic patients, with implications in
treatment efficacy and safety. Moreover, weight loss has been shown to have a
positive effect on psoriasis severity and response to treatment. The aim of this
review is to synthesize the current evidence on the association between psoriasis
and obesity, exploring the physiopathological mechanisms that link both diseases
and highlighting the importance of obesity control in the efficacy and safety of
systemic treatment of psoriasis. All clinicians must be aware of this
association, so they can recognize it and provide the patients a proper follow-up
and multidisciplinary approach when needed.
PMID- 26422426
TI - Systematic review on safety and drug interaction of herbal therapy in
hyperlipidemia: a guide for internist.
AB - Because of reporting high side effects related to biosynthetic drugs, recent
attention has been paid to the use of herbs instead of chemical drugs to balance
serum lipids. The present systematic review aimed to evaluate the safety of
herbal medicines and also to assess drug interaction in herbal therapy in
treating hyperlipidemia. The international research databases including MEDLINE;
Google scholar, Web of Science SciVerse Scopus (SCOPUS); EBSCO Academic Search;
Cochrane Central Register of Controlled Trials (CENTRAL); and a Chinese database
(China Network Knowledge Infrastructure [CNKI]) were searched from their
respective inceptions up to September 2014 with the search terms of
"hyperlipidemia", "herbal medicine", "medicine traditional", "extract plant",
"Traditional Medicine" and "Chinese Herbal Medicine" without narrowing or
limiting search elements. A total of 85 randomized clinical trials (RCTs) studies
were finally assessed on human subjects. A notable number of herbal drugs that
are commonly used as an anti-hyperlipidemia agent may be interacted with a
variety of biosynthetic drugs. In this regard, the most common reported herb-drug
reactions were related to anticoagulants, antidepressants, anti-epileptic, anti
inflammatory, and/or even antihypertension and anti-lipidemic drugs. Also, a
considerable number of anti-lipidemic drugs of plants origin may be accompanied
with metabolic disturbances and serious complications within pregnancy and breast
feeding. The main fundamental principles for administration of these drugs
include physicians' complete awareness of the effects and interactions of these
drugs, educating people not taking these drugs arbitrarily, and closely
monitoring the verification and distribution of the drugs in the society.
PMID- 26422427
TI - In children with Hashimoto's thyroiditis the evolution over time of thyroid
status may differ according to the different presentation patterns.
AB - AIM: to report the salient literature news concerning the relationships between
thyroid function presenting patterns and subsequent biochemical evolution of
Hashimoto's thyroiditis (HT) in pediatric age. DESIGN: the most recent reports
from pediatric literature concerning biochemical thyroid function patterns at HT
presentation and their spontaneous changes over time were analyzed and shortly
commented. RESULTS: from the analysis of pediatric literature on this theme, it
emerges that HT in children may present with a very heterogeneous biochemical
picture ranging from overt hypothyroidism to overt hyperthyroidism. The
presenting biochemical pattern may also condition its subsequent evolution over
time. CONCLUSIONS: a) the most common biochemical pattern at HT diagnosis in
children is euthyroidism, followed by overt hypothyroidism, subclinical
hypothyroidism (SH) and hyperthyroidism; b) the association with HT negatively
affects the evolution over time of SH; c) in the cases with either Turner
syndrome or Down syndrome the evolution over time of SH is more severe than in
those without these chromosomopathies.
PMID- 26422428
TI - Quality of life and functional disability in patients with interstitial lung
disease related to Systemic Sclerosis.
AB - BACKGROUND: Systemic Sclerosis (SSc) is a connective disease impairing
respiratory function. SSc worsens patients' Health Assessment Questionnaire (HAQ
DI), Short Form 36 Physical and Mental Component Summary (SF36-PCS and SF36-MCS).
The aim of this work is to verify whether there is correlation between quality of
life and lung interstitiopathy in SSc patients. METHODS: SF36 and HAQ-DI were
given to each patient (48 in all). Lung involvement was evaluated with Baseline
Dyspnea Index (BDI), spirometry and pulmonary fibrosis radiological assessment
(PFRA). Correlations between SF36, HAQ-DI and lung involvement severity were
investigated with Spearman's rank test. A p-value<0.05 was considered
statistically significant. RESULTS: SF36-PCS and SF36-MCS correlate with BDI
(respectively rho=0.553 p=0.0001; rho=0.357 p=0.0150). The best correlating SF36
subsets are Physical Role (rho =0.566 p<0.0001) and Bodily Pain (rho=0.444
p=0.0020). BDI correlates with HAQ-DI (rho=-0.655 p<0.0001). No statistically
significant correlation was found between SF36, HAQ-DI and spirometrical values
nor PFRA. CONCLUSIONS: The SSc patients enrolled have an impaired quality of life
as widely demonstrated in literature. Quality of life reduction and functional
ability decrease are only related to respiratory subjective impairment (assessed
by BDI). Actually no correlation with objective lung damage (assessed by
spirometry and PFRA) was detected.
PMID- 26422429
TI - Chronic pain treatment and scrambler therapy: a multicenter retrospective
analysis.
AB - BACKGROUND AND AIM: Scrambler Therapy is a novel neuromodulation that works by
electrocutaneous stimulation in a non-invasive manner through C fibers surface
receptors. It substitutes pain information with synthetic "non pain" information.
The primary aim of this study was to analyze the efficacy and safety of Scrambler
Therapy after ten sessions related to different usage conditions and different
learning curves that occur in a multi-center study. METHODS: 201 patients have
been treated with Scrambler Therapy. All the patients were suffering from chronic
pain with a mean pain NRS of 7.41 (SD 2.06) before treatment. Main causes of
chronic pain: post herpetic neuralgia 18.40 %, chronic low back pain (LBP)
37.31%, polyneuropathy 10.94%, and peripheral neuropathy 14.42 %. The remaining
18.93 % included chronic pain due to other causes. RESULTS: The difference
between pre-treatment NRS 7.41 (SD 2.06) and post-treatment 1.60 (SD 2.22) was
statistically significant (P< 0.0001). The mean number of sessions per patient
was 10, but 39 had complete absence of pain sooner and used fewer sessions. Only
7 patients stopped treatment due to lack of results, and 2 for personal reasons
not ascribable to the treatment. Stimulation pain score of 0 during treatment,
and not just pain reduction, predicts long term effectiveness, so this must be
pursued by optimizing electrode positioning and correct fine-tuning of
stimulation intensity. CONCLUSION: Scrambler Therapy is an efficient and safe
alternative for several different types of refractory chronic neuropathic pain,
with a very rare possibility of adverse events.
PMID- 26422430
TI - Metabolic syndrome and its association with left ventricular dysfunction in
patients with left bundle branch block.
AB - BACKGROUND: The present study and for the first time hypothesizes that the
patients with left bundle branch block (LBBB) suffer considerably from metabolic
syndrome (MetS) and this metabolic phenomenon can be associated with cardiac
dysfunction status such as ventricular dilation and reduced left ventricular
ejection fraction (LVEF) in these patients. METHODS: A retrospective study was
conducted on 220 consecutive patients with diagnosed LBBB. MetS status was
diagnosed using the Adult Treatment Panel III of the National Cholesterol
Education Program criteria. Systolic function state was assessed using two
dimensional echocardiography. RESULTS: The overall prevalence of MetS among
studied LBBB patients was 16.8%. Regarding left ventricular functional status in
the two groups, the mean LVEF in the groups with and without MetS was 37.03 +/-
9.09% and 43.43 +/- 15.62% with a significant difference (p = 0.017). However,
left ventricular dilation was similarly detected in both groups with and without
MetS (21.6% versus 30.6%, p = 0.273). Multivariable linear regression model
showed subjects with MetS had lower LVEF in the presence of confounders (Beta =
6.915, p = 0.039). CONCLUSION: A notable number of LBBB patients suffered from
MetS and this metabolic phenomenon is significantly associated with lowering left
ventricular function in LBBB patients.
PMID- 26422431
TI - Prevalence, main determinants, and early outcome of patients with atrial
fibrillation hospitalized with ischemic stroke: evaluation of the value of risk
assessment scores for predicting risk of stroke or major bleeding following
anticoagulation therapy.
AB - BACKGROUND: Despite controllable nature of atrial fibrillation in most patients,
it increases the risk of atrial thrombosis leading to ischemic stroke. The
researchers assessed the underlying risk factors for brain stroke and also major
bleeding in patients with ischemic stroke and atrial fibrillation. METHODS: Among
900 patients hospitalized with the diagnosis of ischemic brain stroke between
2013 and 2014, 100 patients had atrial fibrillation that included into this cross
sectional study. The risk of stroke and major bleeding was assessed using CHA2DS2
VASc and HAS-BLED risk scores, respectively; but new stroke was not considered.
RESULTS: Of 900 patients with evidences of ischemic stroke, 100 had atrial
fibrillation with an overall prevalence of 11.1%. Mean CHA2DS2-VASc score was
4.35 +/- 1.76 that the total score was >= 2 points in 93% of subjects showing
necessity to anticoagulation therapy in 93% of the patients before recent stroke.
Mean HAS-BLED score was 2.83 +/- 1.30 that was >= 3 in 61% indicating risk of
bleeding in 61% of all patients. 31% of the patients had previous history of
atrial fibrillation, but only less than half of them (51%) were under treatment
with warfarin, and also the measured INR was lower than the therapeutic range in
95.5% of individuals on warfarin therapy. In-hospital mortality was reported in
9% of all study subjects. The main determinants of early mortality included
history of stroke, renal failure, presence of coronary artery disease,
acetylsalicylic acid use, and Clopidogrel use. The analysis using the ROC curve
showed that both CHA2DS2-VASc score (AUC = 0.788) and HAS-BLED score (AUC =
0.960) could strongly predict in-hospital mortality. CONCLUSION: The patients
with atrial fibrillation hospitalized with ischemic stroke showed an important
absolute risk of further stroke and early mortality. Despite substantiated
advantages of warfarin prophylaxis, its limited application is still very common.
PMID- 26422432
TI - Overcrowding and clinical risk in Emergency Departments. A model for the
reduction in NEDOCS: preliminary results.
AB - Overcrowding in Emergency Departments represents one of the main concerns in
effective hospital management today. In order to reduce this phenomenon, this
study experimented with a new organizational model that exploited available
resources, without incurring additional costs. Through the redistribution of
hospital beds, it was possible to reduce access blocks in the Emergency
Department of the test hospital. The observational period of this study was of
120 days, and daily surveys of crowding were performed at predetermined
intervals. The measurement of overcrowding was calculated utilizing the National
Emergency Department Overcrowding Score. The findings reveal a significant
reduction in overcrowding due to an increase of only 6 beds in the Emergency
Department. Currently, it is known that the principle cause of overcrowding is
attributed to a lack of hospital beds for inpatients. Numerous studies have shown
that through the lengthening of inpatient hospitalizations it is possible to
improve crowding levels in Emergency Department. This findings of this study
robustly demonstrate that a small increase in the number of available beds
available in emergency department leads to a decrease in all variables of the
NEDOCS, and in particular, that of the severely and dangerous overcrowding score.
PMID- 26422433
TI - Tubal ectopic pregnancy: our experience from 2000 to 2013.
AB - In this paper we summarize our experience in diagnosis and treatment of 402
retrospectively collected tubal EP and review the most recent topics from the
literature. Systemic Methotrexate (MTX) was effective in 56 out of 65 patients
(failure rate 13.8%), in whom hCG level was significantly lower when compared to
the failure group (p<0,05); we performed 299 salpingectomies, 297 of whom through
laparoscopic approach. MTX single-dose is safe and effective in eligible
patients; surgery represents the treatment of most of the EPs, mainly through
laparoscopic approach.
PMID- 26422434
TI - Immunization practices in athletes.
AB - INTRODUCTION: Immunization practices of athletes is a topic of growing interest
in preventive medicine. Several reasons contribute to support such statement
including: the demonstrated decrease of the immune response of athletes, the
recent increase in vaccine-preventable diseases, the increasing mobility of
professional athletes and coaches and sports doctors' frequent lack of awareness
of on the issue of athletes' immune prophylaxis. RESULTS: This review offers a
concise and schematic framework to the immunization practices in athletes, based
on the most recent scientific evidences and the vaccine schedules proposed by
international organizations and scientific societies including the recent "Life
Vaccination Schedule" proposed by four Italian Scientific Societies and
Professional Associations. CONCLUSION: vaccination in athletes, if correctly
managed, represents a powerful, costly and long lasting tool for athletes sport
teams.
PMID- 26422435
TI - Hypoglicemia related to big Haemangiopericitoma: a difficult diagnostic
definition.
AB - We describe the case of a 91 years old woman admitted to our department for
dyspnea associated with drowsiness. At the admission to the Emergency Room the
patient stay in a comatose state and blood tests performed showing severe
hypoglycemia (38 mg/dl at admission in non diabetic patient). Anamnestic history:
multifactorial anemia; frequent hospitalizations for heart failure; AMI treated
with stenting; in 1986 Haemangiopericytoma resection in the right iliac region;
in 2006 palliative surgery for recurrence with residual mass. Blood tests showed
lower levels of insulin and normal C- peptide serum concentration in
correspondence of low glucose concentration (in relation to continuous and
adequate parenteral nutrition), IGF 1 and GH level was respectively suppressed
(IGF1=47 ng/ml whit normal range 97-331 ng/ml) and normal/low (GH 0.43 uUI/mL
whit normal range 0.06-14.00 uUI/mL).Therefore hypoglycemia appeared related to
paraneoplastic production of IGF -2.
PMID- 26422436
TI - Occult nasolacrimal duct ectasia in a child with acute sinusitis:
clinicopathological considerations and literature review.
AB - BACKGROUND: Enlargement of the nasolacrimal duct (NLD) in the absence of neoplasm
is rare. As there are few reports on this condition in the literature, its
pathologic significance and proper management remain unclear. We report a case of
asymptomatic NLD enlargement incidentally discovered on high resolution computed
tomography scan performed for a complicated acute sinusitis. METHODOLOGY: Case
report and literature review. RESULTS AND CONCLUSIONS: NLD enlargement, defined
as a truly isolated asymptomatic dilatation of the NLD, is rarely encountered.
Etiology and clinical significance are unclear although the absence of
nasolacrimal pathway or sinonasal disease and radiological findings of bone
remodelling suggest that it may be congenital. In such cases, diagnosis may be
incidental and based on imaging studies, and the term NLD ectasia seems to be
more appropriate to describe this distinct entity. NLD enlargement may favour
osteomeatal complex obstruction, thus leading to severe acute sinusitis.
PMID- 26422437
TI - Fall from height: a case report.
AB - The manuscript reports the case of a 16-year-old boy who fell from a height of 15
meters while having a cellphone conversation. Surprisingly, only minor injuries
were reported. Prognostic factors related to falls from height are still debated;
the present case is a further contribution to the discussion.
PMID- 26422438
TI - Integrated treatment of the severely injured patient with coexistent
comorbidities. A case report and literature review.
AB - Major trauma represents a paradigmatic clinical condition, needing
multidisciplinary and structured approach. When a patient is affected by
significant comorbidities such as diabetes mellitus and other conditions that
compromise the immune competence the risk of infections in the presence of
exposed fractures is remarkably high. Although usually managed by
multidisciplinary teams, these patients often have unfavorable functional
outcomes. We describe here the case of a young diabetic and immunosuppressed man,
treated for a destroying injury of the left lower limb, with more than 60
centimeters of multiple fractures exposition. The prompt and fast integration of
several different competences led to favorable functional outcome, without any
severe local or systemic complication. Therefore, in severely injured patients,
especially when affected by significant comorbidities, a quick and highly
integrated treatment, provided by a polyspecialistic team, is crucial for
reducing unfavorable outcomes and improving the recovery rate.
PMID- 26422439
TI - The "atrial dancing": echocardiographic diagnosis of electrocardiographic query.
AB - The direct observation of the cardiac structure through the echocardiographic
exam offers, in some cases, the advantage to resolve difficult diagnostic
definition. In this paradigmatic case we emphasize as an accurate observation of
the echocardiographic figures and movies can resolve also an electrocardiographic
query.
PMID- 26422440
TI - The Italian Code of Medical Deontology: characterizing features of its 2014
edition.
AB - The latest edition of the Italian Code of Medical Deontology has been released by
the Italian Federation of the Registers of Physicians and Dentists in May 2014
(1). The previous edition of the Italian Code dated back to 2006 (2), and it has
been integrated and updated by a multi-professional and inter-disciplinary panel
involving, besides physicians, representatives of scientific societies and trade
unions, jurisconsults and experts in bioethics....
PMID- 26422441
TI - Informed consent: Do not be afraid.
AB - Informed consent is the cornerstone of the doctor-patient relationship. At least
this is how it is presented in theory. In practice, doctors struggle with their
obligation to inform their patient before obtaining their approval prior to a
medical intervention. In Taiwan, the culture is often mentioned to justify the
doctor's reluctance to speak openly with their patient. Invoking the importance
of the family in the society, doctors tend to rely less on their patients and
more on their relatives to make important decisions. Yet, the cultural argument
for not seeking the patients' informed consent sounds more like a mere excuse
than the real cause of the difficulties doctors face today in obtaining their
patients' consent. This paper argues that today the doctors in Taiwan are mostly
governed by the same fear that was the rule in the USA and Europe until the
1980s. It may be time for changing the paradigm, admitting that patients are able
to handle even the most dramatic diagnosis. It seems also important to get away
from the sterile opposition of doctor's paternalism versus patient's autonomy and
to introduce a true partnership between doctors and patients.
PMID- 26422443
TI - Geriatric polypharmacy in Taiwan.
PMID- 26422442
TI - Quality of life and its determinants for heroin addicts receiving a methadone
maintenance program: Comparison with matched referents from the general
population.
AB - BACKGROUND/PURPOSE: Quality of life (QoL) is found to be lower in heroin addicts;
however, few studies examine detailed QoL performance and related factors in
heroin patients attending a methadone maintenance treatment program (MMTP). The
study thus aimed to explore QoL and its determinants for publicly-funded and self
paid patients attending an MMTP. METHODS: Participants were recruited in Jianan
Psychiatric Center, Tainan, Taiwan, during their first clinic visit for the MMTP.
Age-, sex-, education-, and municipality-matched referents were collected from
the 2001 Taiwan National Health Interview Survey database. The participants had a
mean age of 38.29 years [standard deviation (SD) = 7.65 years] for publicly
funded (n = 129) and 37.97 years (SD = 7.16 years) for self-paid (n = 105) MMTP
patients. Matched referents (n = 217) were 37.74 years (SD = 7.44 years). All
participants were measured with the brief version of the World Health
Organization's Quality of Life (WHOQOL-BREF) assessment. MMTP patients
additionally went through tests for the hepatitis B virus, hepatitis C virus, and
human immunodeficiency virus (HIV). RESULTS: Both publicly-funded and self-paid
MMTP patients had lower QoL scores than their matched counterparts in the
physical and psychological domains (p < 0.05) after control for confounding by
age, sex, education, and municipality. Detailed individual item analyses showed
that publicly-funded MMTP patients had lower scores for almost all items related
to the physical, psychological, and social domains as compared to the referents
because of HIV infection (p < 0.05). CONCLUSION: To improve the QoL of heroin
users coming for MMTP, we recommend that clinicians pay attention to the
comorbidity of HIV infection and individual items/facets.
PMID- 26422445
TI - Emotional Aspects of Never Events.
PMID- 26422444
TI - The role of Smad3 in the fibrotic phenotype in human vocal fold fibroblasts.
AB - OBJECTIVES/HYPOTHESIS: To investigate the role of Smad3 as a regulator of
transforming growth factor (TGF)-beta1-mediated cell activities associated with
fibrosis in normal human vocal fold fibroblasts. We also sought to confirm the
temporal stability of Smad3 knockdown via small inhibitor ribonucleic acid
(siRNA). Vocal fold fibroblasts were employed to determine the effects of Smad3
knockdown on TGF-beta1-mediated migration and contraction, as well as regulation
of connective tissue growth factor (CTGF). We hypothesized that Smad3 is an ideal
candidate for therapeutic manipulation in vivo based on its role in fibrosis.
STUDY DESIGN: In vitro. METHODS: Knockdown of Smad3 via siRNA was performed in
our normal human vocal fold cell line. Three-dimensional collagen gel contraction
and scratch assays were employed to determine the role of Smad3 on TGF-beta1
mediated contraction and migration, respectively. The role Smad3 in the induction
of CTGF was characterized via sodium dodecyl sulfate polyacrylamide gel
electrophoresis. The effects of Smad3 signaling on Smad7 messenger (m)RNA and
protein were also quantified. RESULTS: Smad3 knockdown was temporally-stable up
to 72 hours (P < 0.001), diminished TGF-beta1-mediated collagen gel contraction
and migration, and blunted induction of CTGF, but it had no effect on TGF-beta1
mediated Smad7 mRNA or protein induction. CONCLUSION: Transforming growth factor
beta1 stimulated profibrotic cell activities in our cell line and these actions
were largely reduced with Smad3 knockdown. These data provide continued support
for therapeutic targeting of Smad3 for vocal fold fibrosis because it appears to
regulate the fibrotic phenotype. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:1151
1156, 2016.
PMID- 26422446
TI - Offering statins to a population attending health checks with a 10-year
cardiovascular disease risk between 10% and 20.
AB - BACKGROUND: In 2014 the UK National Institute for Health and Care Excellence
recommended reducing the threshold for offering statin therapy to patients from a
10-year modelled risk of cardiovascular disease (CVD) of 20% to 10%. AIM: To
describe the response of patients in UK primary care with a CVD risk between 10%
and 20% to an invitation to attend a consultation to discuss statins. DESIGN AND
SETTING: Review of electronic medical records at one GP practice in the East of
England. METHOD: We invited all patients who had attended an NHS Health Check at
the practice, had a QRisk((r)) score between 10% and 20%, and were not prescribed
statins to attend designated clinics in the practice to discuss starting statins.
We reviewed the medical records to identify those who had attended the clinics
and those who had chosen to start a statin. RESULTS: Of 410 patients invited, 100
(24.4%) patients attended the designated clinics and 45 (11%) chose to start a
statin. Those who chose to start a statin were older and with a higher QRisk((r))
than those who did not. Among those who attended, individuals who started a
statin had a higher QRisk((r)) than those who did not and were more likely to be
current or ex-smokers. CONCLUSIONS: The proportion choosing to start a statin was
substantially lower than previously estimated. Large population-based studies
with long-term follow-up are needed to assess the impact on health and workload
of this change in guidance.
PMID- 26422447
TI - Development and evaluation of alginate-chitosan gastric floating beads loading
with oxymatrine solid dispersion.
AB - Oxymatrine (OM) can be metabolized to matrine in gastrointestinal ileocecal valve
after oral administration, which affects pharmacological activity and reduce
bioavailability of OM. A type of multiple-unit alginate-chitosan (Alg-Cs)
floating beads was prepared by the ionotropic gelation method for gastroretention
delivery of OM. A solid dispersion technique was applied and incorporated into
beads to enhance the OM encapsulation efficiency (EE) and sustain the drug
release. The surface morphology and internal hollow structure of beads were
evaluated using optical microscopy and scanning electron microscopy (SEM). The
developed Alg-Cs beads were spherical in shape with hollow internal structure and
had particle size of 3.49 +/- 0.09 mm and 1.33 +/- 0.09 mm for wet and dried
beads. Over 84% of the optimized OM solid dispersion-loaded Alg-Cs beads were
able to continuously float over the simulated gastric fluid for 12 h in vitro.
The OM solid dispersion-loaded Alg-Cs beads showed drug EE of 67.07%, which was
much higher than that of beads loading with pure OM. Compared with the immediate
release of OM capsules and pure OM-loaded beads, the release of OM from solid
dispersion-loaded Alg-Cs beads was in a sustained-release manner for 12 h.
Prolonged gastric retention time of over 8.5 h was achieved for OM solid
dispersion-loaded Alg-Cs floating beads in healthy rabbit in in vivo floating
ability evaluated by X-ray imaging. The developed Alg-Cs beads loading with OM
solid dispersion displayed excellent performance features characterized by
excellent gastric floating ability, high drug EE and sustained-release pattern.
The study illustrated the potential use of Alg-Cs floating beads combined with
the solid dispersion technique for prolonging gastric retention and sustaining
release of OM, which could provide a promising drug delivery system for gastric
specific delivery of OM for bioavailability enhancement.
PMID- 26422448
TI - Campylobacter species in animal, food, and environmental sources, and relevant
testing programs in Canada.
AB - Campylobacter species, particularly thermophilic campylobacters, have emerged as
a leading cause of human foodborne gastroenteritis worldwide, with Campylobacter
jejuni, Campylobacter coli, and Campylobacter lari responsible for the majority
of human infections. Although most cases of campylobacteriosis are self-limiting,
campylobacteriosis represents a significant public health burden. Human illness
caused by infection with campylobacters has been reported across Canada since the
early 1970s. Many studies have shown that dietary sources, including food,
particularly raw poultry and other meat products, raw milk, and contaminated
water, have contributed to outbreaks of campylobacteriosis in Canada.
Campylobacter spp. have also been detected in a wide range of animal and
environmental sources, including water, in Canada. The purpose of this article is
to review (i) the prevalence of Campylobacter spp. in animals, food, and the
environment, and (ii) the relevant testing programs in Canada with a focus on the
potential links between campylobacters and human health in Canada.
PMID- 26422449
TI - Diagnostic accuracy of capnography during high-frequency ventilation in neonatal
intensive care units.
AB - BACKGROUND AND OBJECTIVE: High-frequency ventilation (HFV) is a powerful tool for
CO2 elimination, and thus requires careful monitoring of CO2 . Our aim was to
assess the diagnostic accuracy (correlation, agreement, and trending) of
continuous distal capnography (dCap) with PaCO2 in infants ventilated with HFV.
DESIGN: This was a prospective, observational, multicenter study. dCap was
compared with simultaneous PaCO2 ("gold standard") drawn from indwelling arterial
line for patient care in term and preterm infants ventilated with HFV. dCap was
obtained via the side-port of a double-lumen endotracheal-tube by a Microstream
capnograph with specially designed software for HFV. RESULTS: Twenty-four infants
participated in the study (median [range] gestational age [GA]: 26.8 [23.6-38.6]
weeks). Analysis included 332 measurements. dCap was in correlation (r = 0.70, P
< 0.001) but with less than adequate agreement (mean difference +/- SD of the
differences: -11.7 +/- 10.3 mmHg) with PaCO2 . Comparable findings were found in
the subgroup of infants <1,000 g (n = 240 measurements). Correlations were
maintained in severe lung disease. Changes in dCap and in PaCO2 for consecutive
measurements within each patient were correlated (r = 0.63, P < 0.001). Area
under the receiver operating curves (ROC) for dCap to detect high (>60 mmHg) or
low (<30 mmHg) PaCO2 was 0.83 (CI: 0.76-0.90) and 0.88 (CI: 0.79-0.97),
respectively; P < 0.001. CONCLUSIONS: Our prospective study suggests that
continuous dCap in infants ventilated with HFV may be helpful for trends and
alarm for unsafe levels of PaCO2 . dCap is only a complimentary tool and cannot
replace PaCO2 sampling because the agreement between these measurements was less
than adequate.
PMID- 26422450
TI - A Technical Assistance Framework to Facilitate the Delivery of Integrated
Behavioral Health Services in Federally Qualified Health Centers (FQHCs).
AB - An implementation approach, featuring direct, onsite technical assistance is
described, and findings from a pilot study assessing the capability of Federally
Qualified Health Centers to provide integrated behavioral health services are
presented. Investigators used the Behavioral Health Integration in Medical Care
(BHIMC) index to measure integration at baseline and follow-up at four FQHCs in
New Jersey. Results indicate that the average baseline capability score of 1.95
increased to 2.44 at follow-up, almost one-half point on the five-point BHIMC
index. This pilot project demonstrates that co-occurring capability can be
assessed, and system-wide technical assistance can be delivered to assist FQHCs
in integrating behavioral health services. Future research should test technical
assistance as an implementation strategy to promote the integration of medical
care and behavioral health treatment on a wider scale.
PMID- 26422451
TI - Heterogeneity of biomaterial-induced multinucleated giant cells: Possible
importance for the regeneration process?
AB - Biomaterial-associated multinucleated giant cells (BMGCs) have been found within
the implantation beds of many different biomaterials. However, their exact
differentiation and their involvement in the inflammatory and healing events of
the foreign body response still remain mostly unclear. Silk fibroin (SF)
scaffolds, which induces a tissue reaction involving both macrophages and BMGCs,
was implanted in the subcutaneous connective tissue of four CD-1 mice for 15 days
using an established subcutaneous implantation model. Analysis of macrophage
polarization and BMGCs was performed by immunohistochemcial detection of pro-
(cyclooxygenase-2 (COX-2), C-C chemokine receptor type 7 (CCR7), nuclear factor
"kappa-light-chain-enhancer" (NF-kappaB)) and anti-(heme oxygenase-1 (HO-1) and
mannose receptor (MR, also known as CD206)). Furthermore, histochemical detection
of tartrate-resistant acid phosphatase (TRAP) was conducted to test its
predictive efficiency for the pro-inflammatory differentiation of cells. An
established system for histomorphometrical analysis was used for counting of
BMGCs expressing these molecules. The results show that BMGCs express both pro-
and anti-inflammatory molecules within the implantation beds of SF scaffolds in
comparable numbers, while only statistically significantly lower numbers of TRAP
positive BMGCs were measured in comparison to the BMGCs expressing the above
mentioned molecules. As these data substantiate the heterogeneity of BMGCs, the
question arises to what extent BMGCs can "support" the process of tissue
regeneration. Furthermore, the data prompt the question to what extent TRAP
expression within a biomaterial implantation bed can be seen as a predictive
marker for an inflammatory condition, as in this study no obvious correlation
between TRAP-expression and other pro-inflammatory markers could be observed.
PMID- 26422452
TI - The National Cancer Institute's Dietary Assessment Primer: A Resource for Diet
Research.
AB - This monograph describes the National Cancer Institute's Dietary Assessment
Primer, a web resource developed to help researchers choose the best available
dietary assessment approach to achieve their research objective. All self-report
instruments have error, but understanding the nature of that error can lead to
better assessment, analysis, and interpretation of results. The Primer includes
profiles of the major self-report dietary assessment instruments, including
guidance on the best uses of each instrument; discussion of validation and
measurement error generally and with respect to each instrument; guidance for
choosing a dietary assessment approach for different research questions; and
additional resources, such as a glossary, references, and overviews of
specific/important issues in the field. This monograph also describes some future
research needs in the field of dietary assessment.
PMID- 26422453
TI - Variant Neurogenic Stunned Myocardium in a Young Female After Subarachnoid
Hemorrhage.
AB - Neurogenic stunned myocardium is a significant complication of subarachnoid
hemorrhage. Diagnosis of neurogenic stunned myocardium is complicated by variable
presentation. We present a case of a 23-year-old woman admitted with a
subarachnoid hemorrhage from an arteriovenous malformation and associated
aneurysm. Postoperatively, she developed pulmonary edema and mildly elevated
cardiac biomarkers. Echocardiography showed hypokinesis of the basal left
ventricular segments and normal contraction of the apical left ventricular
segments consistent with a variant form of neurogenic stunned myocardium. We
describe characteristics and outcomes of neurogenic stunned myocardium in this
young patient with arteriovenous malformation-associated aneurysmal subarachnoid
hemorrhage.
PMID- 26422454
TI - Anesthesia in an Aging Infant: Neonatal Progeroid Syndrome.
AB - Neonatal progeroid syndrome is a unique condition wherein features of aging are
apparent in a newborn at birth. It is a very rare genetic disorder. The first
case in India was reported in December 2011. The anesthetic management of any
infant with this condition could not be found in the medical literature.
Independently described by Rautenstrauch and Wiedemann, neonatal progeroid
syndrome poses significant challenges to the anesthesiologist for a variety of
anatomic and physiologic reasons. Coronary and cerebrovascular atherosclerosis
pose significant concerns in such children. Here, we present the successful
anesthetic management of a 6-month-old male infant with neonatal progeroid
syndrome operated on for bilateral inguinoscrotal swellings.
PMID- 26422455
TI - Liver Transplantation Using Dexmedetomidine in a Patient with a History of
Takotsubo Cardiomyopathy.
AB - Takotsubo cardiomyopathy has been described in patients undergoing liver
transplantation. However, the ideal anesthetic management of patients with a
history of takotsubo cardiomyopathy remains unclear, especially in patients
undergoing liver transplantation. We describe the use of dexmedetomidine in a
patient with a history of takotsubo cardiomyopathy undergoing living-donor liver
transplantation.
PMID- 26422456
TI - First Job Search of Residents in the United States: A Survey of Anesthesiology
Trainees' Interest in Academic Positions in Cities Distant from Previous
Residences.
AB - We surveyed anesthesiology residents to evaluate the predictive effect of prior
residence on desired location for future practice opportunities. One thousand
five hundred United States anesthesiology residents were invited to participate.
One question asked whether they intend to enter academic practice when they
graduate from their residency/fellowship training. The analysis categorized the
responses into "surely yes" and "probably" versus "even," "probably not," and
"surely no." "After finishing your residency/fellowship training, are you
planning to look seriously (e.g., interview) at jobs located more than a 2-hour
drive from a location where you or your family (e.g., spouse or
partner/significant other) have lived previously?" Responses were categorized
into "very probably" and "somewhat probably" versus "somewhat improbably" and
"not probable." Other questions explored predictors of the relationships
quantified using the area under the receiver operating characteristic curve (area
under the curve) +/- its standard error. Among the 696 respondents, 36.9% (N =
256) would "probably" consider an academic practice. Fewer than half of those (P
< 0.0001) would "very probably" consider a distant location (31.6%, 99% CI 24.4%
39.6%). Respondents with prior formal research training (e.g., PhD or Master's)
had greater interest in academic practice at a distant location (AUC 0.63 +/-
0.03, P = 0.0002). Except among respondents with formal research training, a good
question to ask a job applicant is whether the applicant or the applicant's
family has previously lived in the area.
PMID- 26422457
TI - Carbon/Silicon Heterojunction Solar Cells: State of the Art and Prospects.
AB - In the last few decades, advances and breakthroughs of carbon materials have been
witnessed in both scientific fundamentals and potential applications. The
combination of carbon materials with traditional silicon semiconductors to
fabricate solar cells has been a promising field of carbon science. The power
conversion efficiency has reached 15-17% with an astonishing speed, and the
diversity of systems stimulates interest in further research. Here, the
historical development and state-of-the-art carbon/silicon heterojunction solar
cells are covered. Firstly, the basic concept and mechanism of carbon/silicon
solar cells are introduced with a specific focus on solar cells assembled with
carbon nanotubes and graphene due to their unique structures and properties.
Then, several key technologies with special electrical and optical designs are
introduced to improve the cell performance, such as chemical doping, interface
passivation, anti-reflection coatings, and textured surfaces. Finally, potential
pathways and opportunities based on the carbon/silicon heterojunction are
envisaged. The aspects discussed here may enable researchers to better understand
the photovoltaic effect of carbon/silicon heterojunctions and to optimize the
design of graphene-based photodevices for a wide range of applications.
PMID- 26422458
TI - Asp1 from Schizosaccharomyces pombe binds a [2Fe-2S](2+) cluster which inhibits
inositol pyrophosphate 1-phosphatase activity.
AB - Iron-sulfur (Fe-S) clusters are widely distributed protein cofactors that are
vital to cellular biochemistry and the maintenance of bioenergetic homeostasis,
but to our knowledge, they have never been identified in any phosphatase. Here,
we describe an iron-sulfur cluster in Asp1, a dual-function kinase/phosphatase
that regulates cell morphogenesis in Schizosaccharomyces pombe. Full-length Asp1,
and its phosphatase domain (Asp1(371-920)), were each heterologously expressed in
Escherichia coli. The phosphatase activity is exquisitely specific: it hydrolyzes
the 1-diphosphate from just two members of the inositol pyrophosphate (PP-InsP)
signaling family, namely, 1-InsP7 and 1,5-InsP8. We demonstrate that Asp1 does
not hydrolyze either InsP6, 2-InsP7, 3-InsP7, 4-InsP7, 5-InsP7, 6-InsP7, or 3,5
InsP8. We also recorded 1-phosphatase activity in a human homologue of Asp1,
hPPIP5K1, which was heterologously expressed in Drosophila S3 cells with a
biotinylated N-terminal tag, and then isolated from cell lysates with avidin
beads. Purified, recombinant Asp1(371-920) contained iron and acid-labile
sulfide, but the stoichiometry (0.8 atoms of each per protein molecule) indicates
incomplete iron-sulfur cluster assembly. We reconstituted the Fe-S cluster in
vitro under anaerobic conditions, which increased the stoichiometry to
approximately 2 atoms of iron and acid-labile sulfide per Asp1 molecule. The
presence of a [2Fe-2S](2+) cluster in Asp1(371-920) was demonstrated by UV
visible absorption, resonance Raman spectroscopy, and electron paramagnetic
resonance spectroscopy. We determined that this [2Fe-2S](2+) cluster is unlikely
to participate in redox chemistry, since it rapidly degraded upon reduction by
dithionite. Biochemical and mutagenic studies demonstrated that the [2Fe-2S](2+)
cluster substantially inhibits the phosphatase activity of Asp1, thereby
increasing its net kinase activity.
PMID- 26422460
TI - Mechanism of dynamic reorientation of cortical microtubules due to mechanical
stress.
AB - Directional growth caused by gravitropism and corresponding bending of plant
cells has been explored since 19th century, however, many aspects of mechanisms
underlying the perception of gravity at the molecular level are still not well
known. Perception of gravity in root and shoot gravitropisms is usually
attributed to gravisensitive cells, called statocytes, which exploit
sedimentation of macroscopic and heavy organelles, amyloplasts, to sense the
direction of gravity. Gravity stimulus is then transduced into distal elongation
zone, which is several mm far from statocytes, where it causes stretching. It is
suggested that gravity stimulus is conveyed by gradients in auxin flux. We
propose a theoretical model that may explain how concentration gradients and/or
stretching may indirectly affect the global orientation of cortical microtubules,
attached to the cell membrane and induce their dynamic reorientation
perpendicular to the gradients. In turn, oriented microtubule arrays direct the
growth and orientation of cellulose microfibrils, forming part of the cell
external skeleton and determine the shape of the cell. Reorientation of
microtubules is also observed in reaction to light in phototropism and mechanical
bending, thus suggesting universality of the proposed mechanism.
PMID- 26422459
TI - Quantitative proteomics unveiled: Regulation of DNA double strand break repair by
EGFR involves PARP1.
AB - BACKGROUND: EGFR inhibition blocks DNA double strand break (DSB) repair but the
detailed mechanisms are still unclear. We asked whether EGFR inhibition blocks
DSB repair by reducing the X-ray-induced phosphorylation of repair proteins using
a phosphoproteomic approach. MATERIALS AND METHODS: Using UT-SCC5 and SAS head
and neck cancer cells we established a differential phosphoproteomic approach for
quantitative analysis of DNA repair proteins by stable isotope labeling with
amino acids. Nuclear phosphoproteins were isolated and analyzed by liquid
chromatography/tandem mass spectrometry. Erlotinib, PD98059 and olaparib were
used to inhibit EGFR, MEK1/2 and PARP1, respectively. PARP1 was knocked down by
siRNA. DSB repair was measured by quantifying residual 53BP1 foci. RESULTS: Over
150 nuclear phosphoproteins were quantified after irradiation, including 24 DNA
repair proteins. Two of these, including PARP1, were consistently reduced in both
cell lines upon erlotinib treatment. PARP1 inhibition or knock-down and EGFR
inhibition resulted in an analog number of residual foci which was not further
increased by combination of both strategies. MEK1/2 inhibition with or without
blockage of EGFR or PARP1 caused similar effects. CONCLUSION: We have established
a powerful, quantitative phosphoproteomic approach to investigate regulatory
mechanisms in DSB repair, dependent on protein phosphorylation after irradiation.
Using this approach we have identified PARP1 as a mediator of EGFR/MEK-dependent
regulation of DSB repair.
PMID- 26422461
TI - Establishing Australian Norms for the Jebsen Taylor Test of Hand Function in
Typically Developing Children Aged Five to 10 Years: A Pilot Study.
AB - AIMS: The aim of this study was to present preliminary normative data for the
Jebsen Taylor Test of Hand Function test (JTTHF) in Australian children.
Normative data provide reference values for comparison of upper limb capacity
when evaluating and planning treatment. METHODS: The JTTHF administration
procedures and materials were standardized. One hundred and two typically
developing children aged 5 to 10 years in Brisbane, Australia, were then assessed
using the JTTHF. RESULTS: Five-year-old children were significantly different to
all other groups (one year age bands), and 6-year-old children were significantly
different from 9-year-old children in the dominant hand. Regression modeling
showed improvements of 0.9 and 0.89 s in JTTHF total time for the dominant and
nondominant hands, respectively, for every 12 months of maturation in 6- to 10
year-old children. CONCLUSIONS: This paper presents preliminary JTTHF norms for
Australian typically developing children 5 years, 6 to 7 years, 8 to 9 years, and
10 years of age.
PMID- 26422462
TI - Patterns of cannabis use in patients with Inflammatory Bowel Disease: A
population based analysis.
AB - BACKGROUND: Tobacco use patterns and effects in patients with Inflammatory Bowel
Disease have been extensively studied, however the role and patterns of cannabis
use remains poorly defined. Our aim was to evaluate patterns of marijuana use in
a large population based survey. METHODS: Cases were identified from the NHANES
database from the National Center for Health Statistics for the time period from
January, 2009 through December, 2010 as having ulcerative colitis or Crohn's
disease, and exact matched with controls using the Propensity Score Module of
SPSS, based on age, gender, and sample weighted using the nearest neighbor
method. RESULTS: After weighting, 2084,895 subjects with IBD and 2013,901 control
subjects were identified with no significant differences in demographic
characteristics. Subjects with IBD had a higher incidence of ever having used
marijuana/hashish (M/H) (67.3% vs. 60.0%) and an earlier age of onset of M/H use
(15.7 years vs. 19.6 years). Patients with IBD were less likely to have used M/H
every month for a year, but more likely to use a heavier amount per day (64.9%
subjects with IBD used three or more joints per day vs. 80.5% of subjects without
IBD used two or fewer joints per day). In multivariable logistic regression,
presence of IBD, male gender, and age over 40 years predicted M/H use.
CONCLUSION: Our study is the first to evaluate marijuana patterns in a large
scale population based survey. Older, male IBD patients have the highest odds of
marijuana use.
PMID- 26422463
TI - Engineering Microbiomes to Improve Plant and Animal Health.
AB - Animal and plant microbiomes encompass diverse microbial communities that
colonize every accessible host tissue. These microbiomes enhance host functions,
contributing to host health and fitness. A novel approach to improve animal and
plant fitness is to artificially select upon microbiomes, thus engineering
evolved microbiomes with specific effects on host fitness. We call this
engineering approach host-mediated microbiome selection, because this method
selects upon microbial communities indirectly through the host and leverages host
traits that evolved to influence microbiomes. In essence, host phenotypes are
used as probes to gauge and manipulate those microbiome functions that impact
host fitness. To facilitate research on host-mediated microbiome engineering, we
explain and compare the principal methods to impose artificial selection on
microbiomes; discuss advantages and potential challenges of each method; offer a
skeptical appraisal of each method in light of these potential challenges; and
outline experimental strategies to optimize microbiome engineering. Finally, we
develop a predictive framework for microbiome engineering that organizes research
around principles of artificial selection, quantitative genetics, and microbial
community-ecology.
PMID- 26422465
TI - Dated Plant Phylogenies Resolve Neogene Climate and Landscape Evolution in the
Cape Floristic Region.
AB - In the context of molecularly-dated phylogenies, inferences informed by ancestral
habitat reconstruction can yield valuable insights into the origins of biomes,
palaeoenvironments and landforms. In this paper, we use dated phylogenies of 12
plant clades from the Cape Floristic Region (CFR) in southern Africa to test
hypotheses of Neogene climatic and geomorphic evolution. Our combined dataset for
the CFR strengthens and refines previous palaeoenvironmental reconstructions
based on a sparse, mostly offshore fossil record. Our reconstructions show
remarkable consistency across all 12 clades with regard to both the types of
environments identified as ancestral, and the timing of shifts to alternative
conditions. They reveal that Early Miocene land surfaces of the CFR were wetter
than at present and were dominated by quartzitic substrata. These conditions
continue to characterize the higher-elevation settings of the Cape Fold Belt,
where they have fostered the persistence of ancient fynbos lineages. The Middle
Miocene (13-17 Ma) saw the development of perennial to weakly-seasonal arid
conditions, with the strongly seasonal rainfall regime of the west coast arising
~6.5-8 Ma. Although the Late Miocene may have seen some exposure of the
underlying shale substrata, the present-day substrate diversity of the CFR
lowlands was shaped by Pliocene-Pleistocene events. Particularly important was
renewed erosion, following the post-African II uplift episode, and the reworking
of sediments on the coastal platform as a consequence of marine transgressions
and tectonic uplift. These changes facilitated adaptive radiations in some, but
not all, lineages studied.
PMID- 26422467
TI - Cultural Beliefs Underlying Medication Adherence in People of Chinese Descent in
the United States.
AB - This article examines the meanings, practices, and cultural beliefs underlying
medication adherence in people of Chinese descent living in the United States.
The narratives were analyzed using interpretive phenomenology, resulting in the
following themes that influenced the communication and behaviors around
medication adherence of the participants: (a) cultural concepts of yin yang
balance and "qi," (b) understandings of Western and Chinese medicine's efficacy
profiles, (c) importance of family and social support, and (d) level of
acculturation. This article discusses the influence of these themes on medication
adherence and proposes that health communication campaigns, interventions, and
doctor-patient communication about increasing medication adherence with people of
Chinese descent should engage these understandings.
PMID- 26422464
TI - Dopamine D3 receptor binding of (18)F-fallypride: Evaluation using in vitro and
in vivo PET imaging studies.
AB - Identification of dopamine D3 receptors (D3R) in vivo is important to understand
several brain functions related to addiction. The goal of this work was to
identify D3R binding of the dopamine D2 receptor (D2R)/D3R imaging agent, (18)F
fallypride. Brain slices from male Sprague-Dawley rats (n = 6) and New Zealand
White rabbits (n = 6) were incubated with (18)F-fallypride and D3R selective
agonist (R)-7-OH-DPAT (98-fold D3R selective). Rat slices were also treated with
BP 897 (68-fold D3R selective partial agonist) and NGB 2904 (56-fold D3R
selective antagonist). In vivo rat studies (n = 6) were done on Inveon PET using
18-37 MBq (18)F-fallypride and drug-induced displacement by (R)-7-OH-DPAT, BP 897
and NGB 2904. PET/CT imaging of wild type (WT, n = 2) and D2R knock-out (KO, n =
2) mice were carried out with (18)F-fallypride. (R)-7-OH-DPAT displaced binding
of (18)F-fallypride, both in vitro and in vivo. In vitro, at 10 nM (R)-7-OH-DPAT,
(18)F-fallypride binding in the rat ventral striatum (VST) and dorsal striatum
(DST) and rabbit nucleus accumbens were reduced by ~10-15%. At 10 MUM (R)-7-OH
DPAT all regions in rat and rabbit were reduced by >=85%. In vivo reductions for
DST and VST before and after (R)-7-OH-DPAT were: low-dose (0.015 mg kg(-1)) DST
22%, VST -29%; high-dose (1.88 mg kg(-1)) DST -58%, VST -77%, suggesting D3R/D2R
displacement. BP 897 and NGB 2904 competed with (18)F-fallypride in vitro, but
unlike BP 897, NGB 2904 did not displace (18)F-fallypride in vivo. The D2R KO
mice lacked (18)F-fallypride binding in the DST. In summary, our findings suggest
that up to 20% of (18)F-fallypride may be bound to D3R sites in vivo.
PMID- 26422466
TI - Patient-Provider Interactions Affect Symptoms in Gastroesophageal Reflux Disease:
A Pilot Randomized, Double-Blind, Placebo-Controlled Trial.
AB - BACKGROUND: It is unclear whether the benefits that some patients derive from
complementary and integrative medicine (CIM) are related to the therapies
recommended or to the consultation process as some CIM provider visits are more
involved than conventional medical visits. Many patients with gastrointestinal
conditions seek out CIM therapies, and prior work has demonstrated that the
quality of the patient-provider interaction can improve health outcomes in
irritable bowel syndrome, however, the impact of this interaction on
gastroesophageal reflux disease (GERD) is unknown. We aimed to assess the safety
and feasibility of conducting a 2 x 2 factorial design study preliminarily
exploring the impact of the patient-provider interaction, and the effect of an
over-the-counter homeopathic product, Acidil, on symptoms and health-related
quality of life in subjects with GERD. METHODS: 24 subjects with GERD-related
symptoms were randomized in a 2 x 2 factorial design to receive 1) either a
standard visit based on an empathic conventional primary care evaluation or an
expanded visit with questions modeled after a CIM consultation and 2) either
Acidil or placebo for two weeks. Subjects completed a daily GERD symptom diary
and additional measures of symptom severity and health-related quality of life.
RESULTS: There was no significant difference in GERD symptom severity between the
Acidil and placebo groups from baseline to follow-up (p = 0.41), however,
subjects who received the expanded visit were significantly more likely to report
a 50% or greater improvement in symptom severity compared to subjects who
received the standard visit (p = 0.01). Total consultation length, perceived
empathy, and baseline beliefs in CIM were not associated with treatment outcomes.
CONCLUSION: An expanded patient-provider visit resulted in greater GERD symptom
improvement than a standard empathic medical visit. CIM consultations may have
enhanced placebo effects, and further studies to assess the active components of
this visit-based intervention are warranted. TRIAL REGISTRATION:
ClinicalTrials.gov NCT01915173.
PMID- 26422468
TI - Identify Beta-Hairpin Motifs with Quadratic Discriminant Algorithm Based on the
Chemical Shifts.
AB - Successful prediction of the beta-hairpin motif will be helpful for understanding
the of the fold recognition. Some algorithms have been proposed for the
prediction of beta-hairpin motifs. However, the parameters used by these methods
were primarily based on the amino acid sequences. Here, we proposed a novel model
for predicting beta-hairpin structure based on the chemical shift. Firstly, we
analyzed the statistical distribution of chemical shifts of six nuclei in not
beta-hairpin and beta-hairpin motifs. Secondly, we used these chemical shifts as
features combined with three algorithms to predict beta-hairpin structure.
Finally, we achieved the best prediction, namely sensitivity of 92%, the
specificity of 94% with 0.85 of Mathew's correlation coefficient using quadratic
discriminant analysis algorithm, which is clearly superior to the same method for
the prediction of beta-hairpin structure from 20 amino acid compositions in the
three-fold cross-validation. Our finding showed that the chemical shift is an
effective parameter for beta-hairpin prediction, suggesting the quadratic
discriminant analysis is a powerful algorithm for the prediction of beta-hairpin.
PMID- 26422471
TI - High-throughput determination of octanol/water partition coefficients using a
shake-flask method and novel two-phase solvent system.
AB - A high-throughput method for determining the octanol/water partition coefficient
(P(o/w)) of a large variety of compounds exhibiting a wide range in
hydrophobicity was established. The method combines a simple shake-flask method
with a novel two-phase solvent system comprising an acetonitrile-phosphate buffer
(0.1 M, pH 7.4)-1-octanol (25:25:4, v/v/v; AN system). The AN system partition
coefficients (K(AN)) of 51 standard compounds for which log P(o/w) (at pH 7.4;
log D) values had been reported were determined by single two-phase partitioning
in test tubes, followed by measurement of the solute concentration in both phases
using an automatic flow injection-ultraviolet detection system. The log K(AN)
values were closely related to reported log D values, and the relationship could
be expressed by the following linear regression equation: log D=2.8630 log K(AN)
0.1497(n=51). The relationship reveals that log D values (+8 to -8) for a large
variety of highly hydrophobic and/or hydrophilic compounds can be estimated
indirectly from the narrow range of log K(AN) values (+3 to -3) determined using
the present method. Furthermore, log K(AN) values for highly polar compounds for
which no log D values have been reported, such as amino acids, peptides,
proteins, nucleosides, and nucleotides, can be estimated using the present
method. The wide-ranging log D values (+5.9 to -7.5) of these molecules were
estimated for the first time from their log K(AN) values and the above regression
equation.
PMID- 26422470
TI - Novel Vitamin D Receptor Mutations in Hereditary Vitamin D Resistant Rickets in
Chinese.
AB - Hereditary 1, 25-dihydroxyvitamin D-resistant rickets (HVDRR), a rare recessive
disease, is caused by mutation in the VDR gene encoding the vitamin D receptor
leading to the resistance to vitamin D. We described a female toddler with
initial presentation of leg tenderness and clinical features of HVDRR including
severe rickets, hypocalcemia and hypophosphatemia without alopecia. Genetic
analysis revealed novel compound heterozygous mutations of p.M4I and p.H229Q in
patient's VDR gene. In cis p.M4I with FOKI-F eliminated both translation start
sites of the VDR protein. The p.H229Q VDR exhibited significantly reduced VDR
transactivation activity with intact dimerization with RXR. Our report expanded
the mutation spectrum of HVDRR, and provided the first case of a benign variant
p.M4I plus a common p.M1T polymorphism leading to a pathogenic allele.
PMID- 26422472
TI - Using Fish Population Metrics to Compare the Effects of Artificial Reef Density.
AB - Artificial reefs continue to be added as habitat throughout the world, yet
questions remain about how reef design affects fish diversity and abundance. In
the present study, the effects of reef density were assessed for fish communities
and sizes of economically valuable Lutjanus campechanus 13 km off Port Mansfield,
Texas, at a reef composed of more than 4000 concrete culverts. The study spanned
from May to June in 2013 and 2014, and sites sampled included natural reefs, bare
areas, and varying culvert patch density categories, ranging from 1-190 culverts.
Abundances of adults and species evenness of juvenile populations differed
between the years. Fish communities did not significantly differ among density
categories; however, highest species richness and total abundances were observed
at intermediate culvert densities and at natural reefs. Whereas the abundance of
L. campechanus did not differ among density categories, mean total lengths of L.
campechanus were greatest at the lower density. Our findings suggest that reefs
should be deployed with intermediate patch density of 71-120 culverts in a 30-m
radius to yield the highest fish abundances.
PMID- 26422469
TI - Adaptation in Toxic Environments: Arsenic Genomic Islands in the Bacterial Genus
Thiomonas.
AB - Acid mine drainage (AMD) is a highly toxic environment for most living organisms
due to the presence of many lethal elements including arsenic (As). Thiomonas
(Tm.) bacteria are found ubiquitously in AMD and can withstand these extreme
conditions, in part because they are able to oxidize arsenite. In order to
further improve our knowledge concerning the adaptive capacities of these
bacteria, we sequenced and assembled the genome of six isolates derived from the
Carnoules AMD, and compared them to the genomes of Tm. arsenitoxydans 3As
(isolated from the same site) and Tm. intermedia K12 (isolated from a sewage
pipe). A detailed analysis of the Tm. sp. CB2 genome revealed various
rearrangements had occurred in comparison to what was observed in 3As and K12 and
over 20 genomic islands (GEIs) were found in each of these three genomes. We
performed a detailed comparison of the two arsenic-related islands found in CB2,
carrying the genes required for arsenite oxidation and As resistance, with those
found in K12, 3As, and five other Thiomonas strains also isolated from Carnoules
(CB1, CB3, CB6, ACO3 and ACO7). Our results suggest that these arsenic-related
islands have evolved differentially in these closely related Thiomonas strains,
leading to divergent capacities to survive in As rich environments.
PMID- 26422473
TI - Emotional Dynamics in the Age of Misinformation.
AB - According to the World Economic Forum, the diffusion of unsubstantiated rumors on
online social media is one of the main threats for our society. The
disintermediated paradigm of content production and consumption on online social
media might foster the formation of homogeneous communities (echo-chambers)
around specific worldviews. Such a scenario has been shown to be a vivid
environment for the diffusion of false claim. Not rarely, viral phenomena trigger
naive (and funny) social responses-e.g., the recent case of Jade Helm 15 where a
simple military exercise turned out to be perceived as the beginning of the civil
war in the US. In this work, we address the emotional dynamics of collective
debates around distinct kinds of information-i.e., science and conspiracy news
and inside and across their respective polarized communities. We find that for
both kinds of content the longer the discussion the more the negativity of the
sentiment. We show that comments on conspiracy posts tend to be more negative
than on science posts. However, the more the engagement of users, the more they
tend to negative commenting (both on science and conspiracy). Finally, zooming in
at the interaction among polarized communities, we find a general negative
pattern. As the number of comments increases-i.e., the discussion becomes longer
the sentiment of the post is more and more negative.
PMID- 26422476
TI - A measurement of the maximal forces in plasmonic tweezers.
AB - Plasmonic tweezers that are designed to trap nanoscale objects create many new
possibilities for single-molecule targeted studies. Numerous novel designs of
plasmonic nanostructures are proposed in order to attain stronger forces and
weaker laser intensity. Most experiments have consisted only of immobilization
observations--that is, particles stick when the laser is turned on and fall away
when the laser is turned off. Studies of the exertable forces were only
theoretical. A few studies have experimentally measured trap stiffness. However,
as far as we know, no studies have addressed maximal forces. In this paper, we
present a new experimental design in which the motion of the trapped particle can
be monitored in either parallel or orthogonal directions to the plasmonic
structure's symmetric axis. We measured maximal trapping force through such
monitoring. Although stiffness would be useful for force-calibration or
immobilization purposes, for which most plasmonic tweezers are used, we believe
that the maximal endurable force is significant and thus, this paper presents
this aspect.
PMID- 26422475
TI - Multiresidue Method for Analysis of beta Agonists in Swine Urine by Enzyme Linked
Receptor Assay Based on beta2 Adrenergic Receptor Expressed in HEK293 Cells.
AB - A novel enzyme-linked receptor assay (ELRA) based on beta2-adrenergic receptor
(beta2-AR) has been developed for rapid and high-throughput detection of beta
adrenergic agonists (beta-agonists) in urine. Human embryonic kidney cells
(HEK293) were introduced as the expression system to enhance the functionality of
the recombinant beta2-AR, and the attempt to detect beta-agonists in swine urine
using such approaches was accomplished unprecedentedly. In this article, a
recombinant porcine beta2-AR was produced in the inner membrane of HEK293 cells
and purified from crude membrane protein by nickel-nitrilotriacetic acid affinity
chromatography. After activity identification, the recombinant receptor was used
in the development of direct competitive ELRA. Several parameters such as
blocking buffer and blocking process were optimized and the performance of the
system was determined. The IC50 concentrations of clenbuterol, salbutamol, and
ractopamine were 34, 53 and 63 MUg/L, and the average recovery rates were 68.2%,
60.3% and 65.5%, respectively. ELRA based on beta2-AR shows a series of
advantages such as safety, easy operation, and high efficiency, making it
promising for the rapid screening of beta-agonists in animal urine.
PMID- 26422477
TI - Rebooting Our Boots on the Ground.
PMID- 26422474
TI - High Treatment Retention Rate in HIV-Infected Patients Receiving Antiretroviral
Therapy at Two Large HIV Clinics in Hanoi, Vietnam.
AB - BACKGROUND: Loss to follow-up (LTFU) is viewed as a major challenge in improving
retention in HIV treatment. In Vietnam, the reasons for disengagement from
clinics and the effect of injection drug use (IDU) on LTFU with unknown outcome
(true LTFU) are not well known. METHODS: Patients receiving antiretroviral
therapy (ART) from two HIV clinics in Hanoi were included in this observational
study between 2007 and 2012, and followed up every 6 months until the end of
2013. The reasons for disengagement from the clinic, and ART status during
imprisonment were investigated in patients with a history of IDU to identify true
LTFU. The retention rate at 6-54 months and true LTFU rate were calculated. Cox
proportional hazards regression models were performed to identify factors
associated with true LTFU. RESULTS: There were 1,431 patients, with a follow-up
time of 4,371 person-years (median 2.49 years). At the end of the follow-up
period, 71 (5.0%) patients died, 79 (5.5%) transferred to other clinics, 16
(1.1%) disengaged from the clinics, and the calculated true LTFU was 45 (3.1%),
with 12-month ART retention rate of 95.3% for the entire study population.
Imprisonment was the most frequent reason for disengagement from the clinics.
True LTFU correlated significantly with low CD4 count and high plasma viral load,
but not history of IDU. CONCLUSION: Imprisonment is a major cause of
disengagement from HIV care among patients with a history of IDU.
PMID- 26422478
TI - Knowing Where Public Health Is Going: Levels and Determinants of Workforce
Awareness of National Public Health Trends.
AB - CONTEXT: Several recent developments are trending in public health, providing an
important window into the future of policy and practice in the field. The extent
to which public health workforce is aware of these trends has not been assessed.
OBJECTIVE: This research examined the extent to which the public health workforce
is familiar with 8 important developments and trends in public health and
explored factors associated with variation in awareness levels. DESIGN: This
study characterizes an observational cross-sectional design, based on analysis of
secondary data collected by the Association of State and Territorial Health
Officials through the Public Health Workforce Interests and Needs Survey (PH
WINS). SETTING: Our study used data from those states for which representative
samples for the local health department (LHD) employees were also available.
PARTICIPANTS: We included survey responses from employees of state health
agencies' central offices and LHDs. MAIN OUTCOME MEASURE: The primary outcome
variable for the analysis was the level of awareness about emerging public health
trends in the public health workforce. RESULTS: Awareness of emerging trends was
lowest for Public Health Systems and Services Research; roughly 1 in 4 employees
were aware of this trend. The second least heard of trends were Health in All
Policies, and cross-jurisdictional sharing. The public health trends about which
the highest proportion of public health employees had heard were implementation
of the Patient Protection and Affordable Care Act and evidence-based public
health practice. Awareness about public health trends was generally higher among
state health agency employees than among LHD employees. Work environment,
supervisory status, employee education, and female gender were significantly
associated with higher awareness levels for both state health agency and LHD
employees. CONCLUSIONS: Public health trends that are important for health
agencies should be brought to the spotlight in national dialogue in order to
increase practitioner involvement in those initiatives.
PMID- 26422479
TI - Not So Strange Bedfellows: How Practice and Academia Together Will Ensure the
Future of the Public Health Workforce.
PMID- 26422480
TI - The Work Experiences of Community Health Professionals: Implications for the
Continued Rollout of the Affordable Care Act.
AB - OBJECTIVE: State health reform (Patient Protection and Affordable Care Act [ACA])
policies may impact the work experiences of community health professionals. We
examine the extent to which community health professional work experiences differ
depending on state Medicaid expansion and health insurance exchange policies.
DESIGN: Public Health Workforce Interests and Needs Survey (PH WINS) (2014)
responses from public health nurses, community health workers, health educators,
and other public health professionals were merged with state ACA Medicaid
expansion and health insurance exchange operations data. We used multivariate
regression to examine the extent to which community health professionals in
states without Medicaid expansion, or expansion states without a state-run health
insurance exchange, reported lower-quality work experiences and less leadership
support than did community health professionals working in Medicaid expansion
states with state-run health insurance exchanges, controlling for worker
characteristics. SETTING: Local and state health departments (SHD) in 37 states.
PARTICIPANTS: 10,246 state health department and 6450 local health department
(LHD) workers. MAIN OUTCOMES: Work satisfaction (job, organization, pay, and job
security), quality of work experiences, leadership support, and impact of the ACA
on work. RESULTS: In adjusted analyses, LHD community health professionals in
states without Medicaid expansion reported worse experiences of leadership
support (beta = -9.83; P < .05). LHD community health professionals in Medicaid
expansion states without state-run health insurance exchange operations reported
lower-quality work experiences (beta = -13.06; P < .01), less leadership support
(beta = -11.52; P < .001), and perceived greater impacts of the ACA on their work
(beta = 9.18; P < .001) than did LHD community health professionals in expansion
states with state-run health insurance exchanges. CONCLUSIONS: Less state control
over health insurance exchange operations or state inaction with respect to
Medicaid expansion may negatively impact LHD community health professional work
experiences and perceptions of leadership support.
PMID- 26422481
TI - Successful Academic-Public Health Practice Collaboration: What Works From the
Public Health Workforce's Perspective.
AB - CONTEXT: Public health departments and academic institutions engage in a range of
cooperative activities that can greatly benefit a public health department and
can often be mutually beneficial. Yet, little is known regarding practitioners'
views of successful academic collaborations. OBJECTIVE: The purpose of this study
was to explore predictors and correlates of beneficial academic collaboration
from the perspective of those on the front lines--the practitioners constituting
the public health workforce. DESIGN: Analysis of the Public Health Workforce
Interests and Needs Survey (PH WINS), a cross-sectional survey of state health
department practitioners, conducted in 2014. PARTICIPANTS: PH WINS is a
nationally representative survey of state health department practitioners. Data
were available for a total of 8718 respondents in 37 states. MAIN OUTCOME
MEASURES: Two main outcome measures were used--(a) whether a respondent reported
collaborating with an academic entity (including faculty/staff/students) in the
past year, and (b) when collaboration did occur, the success of the collaboration
insofar as the respondent perceived the engagement as very helpful. RESULTS:
Health department practitioners (27.2%) reported participating in an academic
practice collaboration. Factors associated with partnering included respondents'
supervisory status, positional duties, and public health background. Of these
respondents, 46.6% reported a successful collaboration. Factors associated with a
successful collaboration included respondents' self-reported job skills and
public health background. CONCLUSION: While characteristics related to a public
health practitioner's position are most significant in predicting whether a
collaboration will occur, characteristics of the individual him- or herself are
more relevant in predicting whether a collaboration will be successful. Public
health managers interested in fostering an environment that promotes a successful
academic-practice collaboration may benefit from ensuring that the public health
practitioners involved in such collaborations are themselves trained in public
health.
PMID- 26422482
TI - The Public Health Workforce Interests and Needs Survey: The First National Survey
of State Health Agency Employees.
AB - CONTEXT: Public health practitioners, policy makers, and researchers alike have
called for more data on individual worker's perceptions about workplace
environment, job satisfaction, and training needs for a quarter of a century. The
Public Health Workforce Interests and Needs Survey (PH WINS) was created to
answer that call. OBJECTIVE: Characterize key components of the public health
workforce, including demographics, workplace environment, perceptions about
national trends, and perceived training needs. DESIGN: A nationally
representative survey of central office employees at state health agencies (SHAs)
was conducted in 2014. Approximately 25,000 e-mail invitations to a Web-based
survey were sent out to public health staff in 37 states, based on a stratified
sampling approach. Balanced repeated replication weights were used to account for
the complex sampling design. SETTING AND PARTICIPANTS: A total of 10,246
permanently employed SHA central office employees participated in PH WINS (46%
response rate). MAIN OUTCOME MEASURES: Perceptions about training needs;
workplace environment and job satisfaction; national initiatives and trends; and
demographics. RESULTS: Although the majority of staff said they were somewhat or
very satisfied with their job (79%; 95% confidence interval [CI], 78-80), as well
as their organization (65%; 95% CI, 64-66), more than 42% (95% CI, 41-43) were
considering leaving their organization in the next year or retiring before 2020;
4% of those were considering leaving for another job elsewhere in governmental
public health. The majority of public health staff at SHA central offices are
female (72%; 95% CI, 71-73), non-Hispanic white (70%; 95% CI, 69-71), and older
than 40 years (73%; 95% CI, 72-74). The greatest training needs include
influencing policy development, preparing a budget, and training related to the
social determinants of health. CONCLUSIONS: PH WINS represents the first
nationally representative survey of SHA employees. It holds significant potential
to help answer previously unaddressed questions in public health workforce
research and provides actionable findings for SHA leaders.
PMID- 26422483
TI - Characterizing Informatics Roles and Needs of Public Health Workers: Results From
the Public Health Workforce Interests and Needs Survey.
AB - OBJECTIVE: To characterize public health workers who specialize in informatics
and to assess informatics-related aspects of the work performed by the public
health workforce. METHODS (DESIGN, SETTING, PARTICIPANTS): Using the nationally
representative Public Health Workforce Interests and Needs Survey (PH WINS), we
characterized and compared responses from informatics, information technology
(IT), clinical and laboratory, and other public health science specialists
working in state health agencies. MAIN OUTCOME MEASURES: Demographics, income,
education, and agency size were analyzed using descriptive statistics. Weighted
medians and interquartile ranges were calculated for responses pertaining to job
satisfaction, workplace environment, training needs, and informatics-related
competencies. RESULTS: Of 10,246 state health workers, we identified 137 (1.3%)
informatics specialists and 419 (4.1%) IT specialists. Overall, informatics
specialists are younger, but share many common traits with other public health
science roles, including positive attitudes toward their contributions to the
mission of public health as well as job satisfaction. Informatics specialists
differ demographically from IT specialists, and the 2 groups also differ with
respect to salary as well as their distribution across agencies of varying size.
All groups identified unmet public health and informatics competency needs,
particularly limited training necessary to fully utilize technology for their
work. Moreover, all groups indicated a need for greater future emphasis on
leveraging electronic health information for public health functions.
CONCLUSIONS: Findings from the PH WINS establish a framework and baseline
measurements that can be leveraged to routinely monitor and evaluate the
ineludible expansion and maturation of the public health informatics workforce
and can also support assessment of the growth and evolution of informatics
training needs for the broader field. Ultimately, such routine evaluations have
the potential to guide local and national informatics workforce development
policy.
PMID- 26422484
TI - Perceptions Regarding Importance and Skill at Policy Development Among Public
Health Staff.
AB - CONTEXT: Policy development is recognized as a core function of public health and
a core competency in formal public health education. However, relatively little
is known nationally about worker perceptions and competencies related to policy
development in the governmental public health workforce. OBJECTIVE: To
characterize perceived importance and presence or absence of competency gaps
related to policy development. DESIGN: As part of the Public Health Workforce
Interests and Needs Survey (PH WINS), a nationally representative stratified
sample of permanently employed state health agency (SHA) central office staff was
created. Descriptive and inferential analyses examined correlates of perceived
importance and competency gaps related to policy development. SETTING AND
PARTICIPANTS: Permanently employed central office employees of SHAs. MAIN OUTCOME
MEASURE: Analyses focus on 2 self-reported measures of perceived importance and
ability related to policy development skills, as well as awareness and
perceptions regarding Health in All Policies (HiAP). RESULTS: Seventy-two percent
of SHA central office staff (95% confidence interval, 71-73) indicated
"influencing policy development" was somewhat or very important to their day-to
day work. Among that group, 35% (95% confidence interval, 34-36) reported that
they were unable to perform this or they considered themselves to be a beginner
at this skill. Approximately three-fourths of staff indicated "understanding the
relationship between a new policy and many types of public health problems" was
somewhat or very important, and 30% of those who did said they were unable to
perform this skill or were a beginner at it. Nationally, one-half of staff have
not heard of HiAP. Among those who have, 86% indicated it was somewhat or very
important to public health, and 41% reported they would like to see more emphasis
on HiAP. CONCLUSIONS: Workforce development, both formal education and on-the-job
training, may benefit from placing a greater emphasis on the development of
policy skills. HiAP is an important approach to policy development.
PMID- 26422485
TI - Perception of Workforce Skills Needed Among Public Health Professionals in Local
Health Departments: Staff Versus Top Executives.
AB - OBJECTIVES: To examine how top executives and staff from local health departments
(LHDs) perceive the importance of various types of workforce skills, and to
assess the differences in the perception of the importance of these workforce
skills between these 2 groups and among LHDs serving different-sized
jurisdictions. DESIGN: Data for this study were drawn from the 2014 Public Health
Workforce Interests and Needs Survey (PH WINS) and the 2015 Forces of Change
survey. While PH WINS collected data from LHD staff, the Forces of Change survey
was administered to LHD top executives. Ratings of perceived importance of
workforce skills from LHD staff and top executives were compared. RESULTS:
Overall, LHD workers at all levels believe that core competencies are important
for their jobs. The perceived importance of these skills differed somewhat across
supervisory level (nonsupervisory staff vs supervisory staff vs top executives).
Communication was rated as one of the most important skills by all groups. For
top executives, ensuring that programs are managed within budget constraints was
the most important skill for their employees. However, this skill was rated much
lower among staff. Policy development skills were rated to be of lowest
importance by LHD leaders and staff. CONCLUSIONS: LHD leaders and staff agree on
the relative importance of some competencies, although they also show some clear
differences in the relative importance that they place on other competencies. It
is essential to strengthen the communication between public health leaders and
staff regarding the importance of workforce skills. More investigation is needed
to assess whether and how gaps in staff competencies are addressed in the
workforce development strategies.
PMID- 26422486
TI - Characterizing the Business Skills of the Public Health Workforce: Practical
Implications From the Public Health Workforce Interests and Needs Survey (PH
WINS).
AB - CONTEXT: Public health financial competencies are often overlooked or
underrepresented in public health training programs. These skills are important
for public health workforce members who are involved in managing resources and
strategic planning and have been defined as key competencies by several national
entities. OBJECTIVE: To characterize business skills among state health agency
employees and examine self-reported skill levels and their association with job
satisfaction, worksite training and development opportunities, and annual salary.
DESIGN: A cross-sectional survey, the Public Health Workforce Interests and Needs
Survey (PH WINS), of state health agency central office employees was conducted
in 2014. Multivariable logistic regression analyses, controlling for job
classification, supervisory status, years of public health practice, annual
compensation, educational attainment, geographic region, and sociodemographic
status, were used to assess the relationship between business skills and training
environment and job satisfaction. Linear regression was used to correlate
business skills and annual compensation. SETTING AND PARTICIPANTS: A total of
10,246 state health agency staff completed a Web-based survey. MAIN OUTCOME
MEASURE: Self-reported proficiency in business skills, job satisfaction,
opportunities for training, and annual salary. RESULTS: The workforce reported
high levels of proficiency in applying quality improvement concepts and managing
change (67.5% and 69.2%, respectively). Half of the respondents reported
proficiency in budget skills (49.3%). Participants who were proficient in
applying quality improvement concepts were significantly more likely to report
job satisfaction (OR = 1.27). A supportive training environment was significantly
associated with business competencies (range of OR = 1.08-1.11). Managing change
(beta = .15) and budget skill proficiency (beta = .37) were significantly
associated with increased yearly compensation. CONCLUSIONS: Public health workers
who self-report proficiency with business skills report increased job
satisfaction, higher annual salary, and a supportive training environment. These
findings support the need for the development of appropriately designed business
skill training opportunities to increase competencies in this critical domain.
PMID- 26422487
TI - ASTHO Affiliates Find Value in PH WINS.
PMID- 26422488
TI - Public Health Wins When We Use Data to Drive Decision Making.
PMID- 26422489
TI - When We Have Data We Can Count on, Everyone WINS.
PMID- 26422490
TI - The Methods Behind PH WINS.
AB - The Public Health Workforce Interests and Needs Survey (PH WINS) has yielded the
first-ever nationally representative sample of state health agency central office
employees. The survey represents a step forward in rigorous, systematic data
collection to inform the public health workforce development agenda in the United
States. PH WINS is a Web-based survey and was developed with guidance from a
panel of public health workforce experts including practitioners and researchers.
It draws heavily from existing and validated items and focuses on 4 main areas:
workforce perceptions about training needs, workplace environment and job
satisfaction, perceptions about national trends, and demographics. This article
outlines the conceptualization, development, and implementation of PH WINS, as
well as considerations and limitations. It also describes the creation of 2 new
data sets that will be available in public use for public health officials and
researchers--a nationally representative data set for permanently employed state
health agency central office employees comprising over 10,000 responses, and a
pilot data set with approximately 12,000 local and regional health department
staff responses.
PMID- 26422491
TI - A Strong Public Health Workforce for Today and Tomorrow.
PMID- 26422492
TI - Application of a Taxonomy to Characterize the Public Health Workforce.
AB - OBJECTIVE: A public health workforce taxonomy was published in 2014 to provide a
standardized mechanism for describing public health worker characteristics. The
Public Health Workforce Interests and Needs Survey (PH WINS) used 7 of the
taxonomy's 12 axes as a basis for its survey response choices, 3 of which are the
focus of this analysis. The purpose of this study was to determine the relative
utility, reliability, and accuracy of the public health workforce taxonomy in
categorizing local and state public health workers using a survey tool. This
specifically included the goal of reducing the number of responses classified as
"other" occupation, certification, or program area by recoding responses into
taxonomy categories and determining potential missing categories for
recommendation to the advisory committee that developed the taxonomy. DESIGN:
Survey questions associated with the occupation, certification, and program area
taxonomy axes yielded qualitative data from respondents who selected "other." The
"other" responses were coded by 2 separate research teams at the University of
Michigan Center of Excellence in Public Health Workforce Studies and NORC at the
University of Chicago. MAIN OUTCOME MEASURES: Researchers assigned taxonomy
categories to all analyzable qualitative responses and assessed the percentage of
PH WINS responses that could be successfully mapped to taxonomy categories.
RESULTS: Between respondent self-selection and research team recoding, the public
health workforce taxonomy successfully categorized 95% of occupation responses,
75% of credential responses, and 83% of program area responses. Occupational
categories that may be considered for inclusion in the taxonomy in the future
include disease intervention specialists and occupations associated with
regulation, certification, and licensing. CONCLUSIONS: The public health
workforce taxonomy performed remarkably well in categorizing worker
characteristics in its first use in a national survey. The analysis provides some
recommendations for future taxonomy refinement.
PMID- 26422493
TI - Job Satisfaction: A Critical, Understudied Facet of Workforce Development in
Public Health.
AB - CONTEXT: The field of public health faces multiple challenges in its efforts to
recruit and retain a robust workforce. Public health departments offer salaries
that are lower than the private sector, and government bureaucracy can be a
deterrent for those seeking to make a difference. OBJECTIVE: The objective of
this research was to explore the relationship between general employee
satisfaction and specific characteristics of the job and the health agency and to
make recommendations regarding what health agencies can do to support recruitment
and retention. DESIGN: This is a cross-sectional study using data collected from
the 2014 Public Health Workforce Interests and Needs Survey (PH WINS). A
nationally representative sample was constructed from 5 geographic (paired
adjacent HHS [US Department of Health and Human Services]) regions and stratified
by population and state governance type. Descriptive and inferential statistics
were analyzed using the balanced repeated replication method to account for the
complex sampling design. A multivariate linear regression was used to examine job
satisfaction and factors related to supervisory and organizational support
adjusting for relevant covariates. SETTING AND PARTICIPANTS: PH WINS data were
collected from state health agency central office employees using an online
survey. MAIN OUTCOME MEASURE: Level of job satisfaction using the Job in General
Scale (abridged). RESULTS: State health agency central office staff (n = 10,246)
participated in the survey (response rate 46%). Characteristics related to
supervisory and organizational support were highly associated with increased job
satisfaction. Supervisory status, race, organization size, and agency tenure were
also associated with job satisfaction. CONCLUSIONS: Public health leaders aiming
to improve levels of job satisfaction should focus on workforce development and
training efforts as well as adequate supervisory support, especially for new
hires and nonsupervisors.
PMID- 26422494
TI - Addressing Urgent Public Health Workforce Needs: Building Informatics Competency
and Strengthening Management and Leadership Skills.
PMID- 26422495
TI - Educational Attainment of the Public Health Workforce and Its Implications for
Workforce Development.
AB - CONTEXT: Educational attainment is a critical issue in public health workforce
development. However, relatively little is known about the actual attainment of
staff in state health agencies (SHAs). OBJECTIVE: Ascertain the levels of
educational attainment among SHA employees, as well as the correlates of
attainment. DESIGN: Using a stratified sampling approaching, staff from SHAs were
surveyed using the Public Health Workforce Interests and Needs Survey (PH WINS)
instrument in late 2014. A nationally representative sample was drawn across 5
geographic (paired adjacent HHS) regions. Descriptive and inferential statistics
were analyzed using balanced repeated replication weights to account for complex
sampling. A logistic regression was conducted with attainment of a bachelor's
degree as the dependent variable and age, region, supervisory status,
race/ethnicity, gender, and staff type as independent variables. SETTING AND
PARTICIPANTS: Web-based survey of SHA central office employees. MAIN OUTCOME
MEASURE: Educational attainment overall, as well as receipt of a degree with a
major in public health. RESULTS: A total of 10,246 permanently-employed SHA
central office staff participated in the survey (response rate 46%). Seventy-five
percent (95% confidence interval [CI], 74-77) had a bachelor's degree, 38% (95%
CI, 37-40) had a master's degree, and 9% (95% CI, 8%-10%) had a doctoral degree.
A logistic regression showed Asian staff had the highest odds of having a
bachelor's degree (odds ratio [OR] = 2.8; 95% CI, 2.2-3.7) compared with non
Hispanic whites, and Hispanic/Latino staff had lower odds (OR = 0.6; 95% CI, 0.4
0.8). Women had lower odds of having a bachelor's degree than men (OR = 0.5; 95%
CI, 0.4-0.6). About 17% of the workforce (95% CI, 16-18) had a degree in public
health at any level. CONCLUSIONS: Educational attainment among SHA central office
staff is high, but relatively few have formal training of any sort in public
health. This makes efforts to increase availability of on-the-job training and
distance learning all the more critical.
PMID- 26422497
TI - Data, Workforce, Action!
PMID- 26422496
TI - Does Money Matter: Earnings Patterns Among a National Sample of the US State
Governmental Public Health Agency Workforce.
AB - CONTEXT: Earnings have been shown to be a critical point in workforce recruitment
and retention. However, little is known about how much governmental public health
staff are paid across the United States. OBJECTIVE: To characterize earnings
among state health agency central office employees. DESIGN: A cross-sectional
survey was conducted of state health agency central office employees in late
2014. The sampling approach was stratified by 5 (paired HHS) regions. Balanced
repeated replication weights were used to correctly calculate variance estimates,
given the complex sampling design. Descriptive and bivariate statistical
comparisons were conducted. A linear regression model was used to examine
correlates of earnings among full-time employees. SETTING AND PARTICIPANTS: A
total of 9300 permanently employed, full-time state health agency central office
staff who reported earnings information. MAIN OUTCOME MEASURE: Earnings are the
main outcomes examined in this article. RESULTS: Central office staff earn
between $55,000 and $65,000 on average annually. Ascending supervisory status,
educational attainment, and tenure are all associated with greater earnings.
Those employed in clinical and laboratory positions and public health science
positions earn more than their colleagues in administrative positions.
Disparities exist between men and women, with men earning more, all else being
equal (P < .001). Racial/ethnic disparities also exist, after accounting for
other factors. CONCLUSIONS: This study provides baseline information to
characterize the workforce and key challenges that result from earnings levels,
including disparities in earnings that persist after accounting for education and
experience. Data from the survey can inform strategies to address earnings issues
and help reduce disparities.
PMID- 26422498
TI - Building and Sustaining Strong Public Health Agencies: Determinants of Workforce
Turnover.
AB - CONTEXT: Workforce shortages have been identified as a priority for US public
health agencies. Voluntary turnover results in loss of expertise and
institutional knowledge as well as high costs to recruit and train replacement
workers. OBJECTIVE: To analyze patterns and predictors of voluntary turnover
among public health workers. DESIGN: Descriptive analysis and linear probability
regression models. PARTICIPANTS: Employees of state health agencies in the United
States who participated in the Public Health Workforce Interests and Needs Survey
(PH WINS). MAIN OUTCOME MEASURES: Intended retirement and voluntary departure;
pay satisfaction; job satisfaction. RESULTS: Nearly 25% of workers reported plans
to retire before 2020, and an additional 18% reported the intention to leave
their current organization within 1 year. Four percent of staff are considering
leaving their organization in the next year for a job at a different health
department. There was significant heterogeneity by demographic, socioeconomic,
and job characteristics. Areas such as administration/management, health
education, health services, social services, and epidemiology may be particularly
vulnerable to turnover. The strongest predictors of voluntary departure were pay
and job satisfaction, which were associated with 9 (P < .001) and 24 (P < .001)
percentage-point decreases, respectively, in the probability to report the
intention to leave. Our findings suggest that if all workers were satisfied with
their job and pay, intended departure would be 7.4%, or less than half the
current 18% rate. Controlling for salary levels, higher levels of education and
longer work experience were associated with lower pay satisfaction, except for
physicians, who were 11 percentage points (P = .02) more likely to be satisfied
with their pay than employees with doctoral degrees. Several workplace
characteristics related to relationships with supervisors, workplace environment,
and employee motivation/morale were significantly associated with job
satisfaction. CONCLUSIONS: Our findings suggest that public health agencies may
face significant pressure from worker retirement and voluntary departures in
coming years. Although retirement can be addressed through recruitment efforts,
addressing other voluntary departures will require focusing on improving pay and
job satisfaction.
PMID- 26422499
TI - Health Resources and Services Administration Perspective on the Public Health
Workforce Interests and Needs Survey.
PMID- 26422500
TI - Loving and Leaving Public Health: Predictors of Intentions to Quit Among State
Health Agency Workers.
AB - CONTEXT: State health agencies play a critical role in protecting and promoting
the health and well-being of the people they serve. To be effective, they must
maintain a highly skilled, diverse workforce of sufficient size and with proper
training. OBJECTIVE: The goal of this study was to examine demographics, job and
workplace environment characteristics, job satisfaction, and reasons for
initially joining the public health workforce as predictors of an employee's
intentions to leave an organization within the next year. DESIGN: This study used
a cross-sectional design. Respondents were selected on the basis of a stratified
sampling approach, with 5 geographic (paired Health and Human Services [HHS]
regions) as the primary strata. Balanced repeated replication was used as a
resampling method for variance estimation. A logistic regression model was used
to examine the correlates of intentions to leave one's organization within the
next year. The independent variables included several measures of satisfaction,
perceptions about the workplace environment, initial reasons for joining public
health, gender, age, education, salary, supervisory status, program area, and
paired HHS region. SETTING AND PARTICIPANTS: The sample for this study consisted
of 10,246 permanently employed state health agency central office employees who
responded to the Public Health Workforce Interests and Needs Survey (PH WINS).
MAIN OUTCOME MEASURE: Considering leaving one's organization within the next
year. RESULTS: Being a person of color, living in the West (HHS regions 9 and
10), and shorter tenure in one's current position were all associated with higher
odds of intentions to leave an organization within the next year. Conversely,
greater employee engagement, organizational support, job satisfaction,
organization satisfaction, and pay satisfaction were all significant predictors
of lower intentions to leave one's organization within the next year.
CONCLUSIONS: Results from this study suggest several variables related to
demographics, job characteristics, workplace environment, and job satisfaction
that are predictive of intentions to leave. Future researchers and state health
agencies should explore how these findings can be used to help with retention of
employees in the state health agency workforce.
PMID- 26422501
TI - Deletion of mineralocorticoid receptors in smooth muscle cells blunts renal
vascular resistance following acute cyclosporine administration.
AB - Calcineurin inhibitors such as cyclosporine A (CsA) are still commonly used after
renal transplantation, despite CsA--induced nephrotoxicity (CIN), which is partly
related to vasoactive mechanisms. The mineralocorticoid receptor (MR) is now
recognized as a key player in the control of vascular tone, and both endothelial
cell- and vascular smooth muscle cell (SMC)-MR modulate the vasoactive responses
to vasodilators and vasoconstrictors. Here we tested whether vascular MR is
involved in renal hemodynamic changes induced by CsA. The relative contribution
of vascular MR in acute CsA treatment was evaluated using mouse models with
targeted deletion of MR in endothelial cell or SMC. Results indicate that MR
expressed in SMC, but not in endothelium, contributes to the increase of plasma
urea and creatinine, the appearance of isometric tubular vacuolization, and
overexpression of a kidney injury biomarker (neutrophil gelatinase--associated
lipocalin) after CsA treatment. Inactivation of MR in SMC blunted CsA--induced
phosphorylation of contractile proteins. Finally, the in vivo increase of renal
vascular resistance induced by CsA was blunted when MR was deleted from SMC
cells, and this was associated with decreased L-type Ca2D channel activity. Thus,
our study provides new insights into the role of vascular MR in renal
hemodynamics during acute CIN, and provides rationale for clinical studies of MR
antagonism to manage the side effects of calcineurin inhibitors.
PMID- 26422502
TI - Relationship of dietary phosphate intake with risk of end-stage renal disease and
mortality in chronic kidney disease stages 3-5: The Modification of Diet in Renal
Disease Study.
AB - KDIGO guidelines recommend dietary phosphate restriction to lower serum phosphate
levels in CKD stages 3-5. Recent studies suggest that dietary phosphate intake is
only weakly linked to its serum concentration, and the relationship of phosphate
intake with adverse outcomes is uncertain. To evaluate this, we used Cox
proportional hazards models to assess associations of baseline 24-h urine
phosphate excretion with risk of end-stage renal disease (ESRD), all-cause
mortality, and mortality subtypes (cardiovascular disease [CVD] and non-CVD)
using the Modification of Diet in Renal Disease data. Models were adjusted for
demographics, CVD risk factors, iothalamate GFR, and urine protein and nitrogen
excretion. Phosphate excretion was modestly inversely correlated with serum
phosphate concentrations. There was no association of 24-h urinary phosphate
excretion with risk of ESRD, CVD, non-CVD, or all-cause mortality. For
comparison, higher serum phosphate concentrations were associated with all-cause
mortality (hazard ratio per 0.7 mg/dl higher, 1.15 [95% CI 1.01, 1.30]). Thus,
phosphate intake is not tightly linked with serum phosphate concentrations in CKD
stages 3-5, and there was no evidence that greater phosphate intake, assessed by
24-h phosphate excretion, is associated with ESRD, CVD, non-CVD, or all-cause
mortality in CKD stages 3-5. Hence, factors other than dietary intake may be key
determinants of serum phosphate concentrations and require additional
investigation.
PMID- 26422503
TI - Proximal tubule-derived colony stimulating factor-1 mediates polarization of
renal macrophages and dendritic cells, and recovery in acute kidney injury.
AB - Infiltrating cells play an important role in both the development of and recovery
from acute kidney injury (AKI). Macrophages and renal dendritic cells are of
particular interest because they can exhibit distinctly different functional
phenotypes, broadly characterized as proinflammatory (M1) or tissue reparative
(M2). Resident renal macrophages and dendritic cells participate in recovery from
AKI in response to either ischemia/reperfusion or a model of selective proximal
tubule injury induced by diphtheria-toxin-induced apoptosis in transgenic mice
expressing the human diphtheria toxin receptor on proximal tubule cells. Colony
stimulating factor-1 (CSF-1) is an important factor mediating the recovery from
AKI, and CSF-1 can stimulate macrophage and dendritic cell proliferation and
polarization during the recovery phase of AKI. The kidney, and specifically the
proximal tubule, is a major source of intrarenal CSF-1 production in response to
AKI. We induced selective deletion of proximal tubule CSF-1 to determine its role
in expansion and proliferation of renal macrophages and dendritic cells and in
recovery from AKI. In both models of AKI, there was decreased M2 polarization,
delayed functional and structural recovery, and increased tubulointerstitial
fibrosis. Thus, intrarenal CSF-1 is an important mediator of macrophage/dendritic
cell polarization and recovery from AKI.
PMID- 26422504
TI - Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate
potassium homeostasis.
AB - Dietary potassium deficiency activates thiazide-sensitive sodium chloride
cotransport along the distal nephron. This may explain, in part, the hypertension
and cardiovascular mortality observed in individuals who consume a low-potassium
diet. Recent data suggest that plasma potassium affects the distal nephron
directly by influencing intracellular chloride, an inhibitor of the with-no
lysine kinase (WNK)-Ste20p-related proline- and alanine-rich kinase (SPAK)
pathway. As previous studies used extreme dietary manipulations, we sought to
determine whether the relationship between potassium and NaCl cotransporter (NCC)
is physiologically relevant and clarify the mechanisms involved. We report that
modest changes in both dietary and plasma potassium affect NCC in vivo. Kinase
assay studies showed that chloride inhibits WNK4 kinase activity at lower
concentrations than it inhibits activity of WNK1 or WNK3. Also, chloride
inhibited WNK4 within the range of distal cell chloride concentration. Mutation
of a previously identified WNK chloride-binding motif converted WNK4 effects on
SPAK from inhibitory to stimulatory in mammalian cells. Disruption of this motif
in WNKs 1, 3, and 4 had different effects on NCC, consistent with the three WNKs
having different chloride sensitivities. Thus, potassium effects on NCC are
graded within the physiological range, which explains how unique chloride-sensing
properties of WNK4 enable it to mediate effects of potassium on NCC in vivo.
PMID- 26422505
TI - Development and validation of a prognostic index for allograft outcome in kidney
recipients with transplant glomerulopathy.
AB - We studied 92 patients with transplant glomerulopathy to develop a prognostic
index based on the risk factors for allograft failure within five years of
diagnosis (Development cohort). During 60 months (median) follow-up, 64 patients
developed allograft failure. A chronic-inflammation score generated by combining
Banff ci, ct and ti scores, serum creatinine and proteinuria at biopsy, were
independent risk factors for allograft failure. Based on the Cox model, we
developed a prognostic index and classified patients into risk groups. Compared
to the low-risk group (median allograft survival over 60 months from diagnosis),
patients in the medium risk group had a hazard ratio of 2.83 (median survival 25
months), while those in the high-risk group had a hazard ratio of 5.96 (median
survival 3.7 months). We next evaluated the performance of the prognostic index
in an independent external cohort of 47 patients with transplant glomerulopathy
(Validation cohort). The hazard ratios were 2.18 (median survival 19 months) and
16.27 (median survival 1.6 months), respectively, for patients in the medium and
high-risk groups, compared to the low-risk group (median survival 47 months). Our
prognostic index model did well in measures of discrimination and calibration.
Thus, risk stratification of transplant glomerulopathy based on our prognostic
index may provide informative insight for both the patient and physician
regarding prognosis and treatment.
PMID- 26422506
TI - Clinical and molecular significance of microvascular inflammation in transplant
kidney biopsies.
AB - The diagnostic criteria for antibody-mediated rejection (AMR) are continuously
evolving. Here we investigated the clinical and molecular significance of
different Banff microvascular inflammation (MVI) scores in transplant kidney
biopsies. A total of 356 patients with clinically indicated kidney transplant
biopsies were classified into three groups based on MVI scores of 0, 1, 2, or
more for Groups 1-3, respectively. Gene expression profiles were assessed using
arrays on a representative subset of 93 patients. The incidence of donor-specific
anti-HLA antibodies was increased from 25% in Group 1 to 36% in Group 2 and to
54% in Group 3. Acute and chronic AMR were significantly more frequent in Group 3
(15% and 35%) compared with the Group 2 (3% and 15%) and Group 1 (0% and 5%),
respectively. Gene expression profiles showed increased interferon-gamma and
rejection-induced, cytotoxic and regulatory T-cell, natural killer cell
associated and donor-specific antibody (DSA)-selective transcripts in Group 3
compared with Groups 1 and 2. There was no significant difference in gene
expression profiles between the Groups 1 and 2. Increased intragraft expression
of DSA-selective transcripts was found in the biopsies of C4d- Group 3 patients.
Thus, an MVI score of 2 or more was significantly associated with a histological
diagnosis of acute and chronic antibody-mediated rejection. Hence, increased
intragraft DSA-selective gene transcripts may be used as molecular markers for
AMR, especially in C4d- biopsies.
PMID- 26422508
TI - Compensatory Growth in Juveniles of Freshwater Redclaw Crayfish Cherax
quadricarinatus Reared at Three Different Temperatures: Hyperphagia and Food
Efficiency as Primary Mechanisms.
AB - Feeding restriction, as a trigger for compensatory growth, might be considered an
alternative viable strategy for minimizing waste as well as production costs. The
study assessed whether juvenile redclaw crayfish Cherax quadricarinatus (initial
weight 0.99 +/- 0.03 g) was able to compensate for feeding restriction at
different temperatures (23 +/- 1, 27 +/- 1 and 31 +/- 1 degrees C).
Hyperphagia, food utilization efficiency, energetic reserves, and hepatopancreas
structure were analyzed. Three temperatures and two feeding regimes (DF-daily fed
throughout the experiment and CF- 4 days food deprivation followed by 4 days of
feeding, intermittently) were tested. The restriction period was from day 1 to
45, and the recovery period was from day 45 to 90. The previously restricted
crayfish held at 23, 27, and 31 +/- 1 degrees C displayed complete body weight
catch-up through compensatory growth following the restriction period with
depressed growth. The mechanisms that might explain this response were higher
feed intake (hyperphagia), and increased food utilization efficiency.
Hepatopancreatic lipids were used as a metabolic fuel and hepatosomatic index was
reduced in the previously restricted crayfish, but recovery at the same level of
unrestricted crayfish occurred after the shift to daily feeding. The highest
temperature affected adversely growth, feed intake, food efficiency, and
metabolism of crayfish, whereas the lowest temperature and feeding restriction
induced a more efficient growth of the crayfish.
PMID- 26422507
TI - Integrated transcriptomic and proteomic analyses uncover regulatory roles of Nrf2
in the kidney.
AB - The transcription factor Nrf2 exerts protective effects in numerous experimental
models of acute kidney injury, and is a promising therapeutic target in chronic
kidney disease. To provide a detailed insight into the regulatory roles of Nrf2
in the kidney, we performed integrated transcriptomic and proteomic analyses of
kidney tissue from wild-type and Nrf2 knockout mice treated with the Nrf2 inducer
methyl-2-cyano-3,12-dioxooleano-1,9-dien-28-oate (CDDO-Me, also known as
bardoxolone methyl). After 24 h, analyses identified 2561 transcripts and 240
proteins that were differentially expressed in the kidneys of Nrf2 knockout mice,
compared with those of wild-type counterparts, and 3122 transcripts and 68
proteins that were differentially expressed in wild-type mice treated with CDDO
Me, compared with those of vehicle control. In the light of their sensitivity to
genetic and pharmacological modulation of renal Nrf2 activity, genes/proteins
that regulate xenobiotic disposition, redox balance, the intra/extracellular
transport of small molecules, and the supply of NADPH and other cellular fuels
were found to be positively regulated by Nrf2 in the kidney. This was verified by
qPCR, immunoblotting, pathway analysis, and immunohistochemistry. In addition,
the levels of NADPH and glutathione were found to be significantly decreased in
the kidneys of Nrf2 knockout mice. Thus, Nrf2 regulates genes that coordinate
homeostatic processes in the kidney, highlighting its potential as a novel
therapeutic target.
PMID- 26422509
TI - [French-Mexican Strategic Partnership for Liver Transplantation].
PMID- 26422511
TI - Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH)
repertoires.
AB - Processes that define immunoglobulin repertoires are commonly presumed to be the
same for all murine B cells. However, studies here that couple high-dimensional
FACS sorting with large-scale quantitative IgH deep-sequencing demonstrate that B
1a IgH repertoire differs dramatically from the follicular and marginal zone B
cells repertoires and is defined by distinct mechanisms. We track B-1a cells from
their early appearance in neonatal spleen to their long-term residence in adult
peritoneum and spleen. We show that de novo B-1a IgH rearrangement mainly occurs
during the first few weeks of life, after which their repertoire continues to
evolve profoundly, including convergent selection of certain V(D)J rearrangements
encoding specific CDR3 peptides in all adults and progressive introduction of
hypermutation and class-switching as animals age. This V(D)J selection and AID
mediated diversification operate comparably in germ-free and conventional mice,
indicating these unique B-1a repertoire-defining mechanisms are driven by
antigens that are not derived from microbiota.
PMID- 26422512
TI - Food odors trigger Drosophila males to deposit a pheromone that guides
aggregation and female oviposition decisions.
AB - Animals use olfactory cues for navigating complex environments. Food odors in
particular provide crucial information regarding potential foraging sites. Many
behaviors occur at food sites, yet how food odors regulate such behaviors at
these sites is unclear. Using Drosophila melanogaster as an animal model, we
found that males deposit the pheromone 9-tricosene upon stimulation with the food
odor apple cider vinegar. This pheromone acts as a potent aggregation pheromone
and as an oviposition guidance cue for females. We use genetic, molecular,
electrophysiological, and behavioral approaches to show that 9-tricosene
activates antennal basiconic Or7a receptors, a receptor activated by many
alcohols and aldehydes such as the green leaf volatile E2-hexenal. We demonstrate
that loss of Or7a positive neurons or the Or7a receptor abolishes aggregation
behavior and oviposition site-selection towards 9-tricosene and E2-hexenal. 9
Tricosene thus functions via Or7a to link food-odor perception with aggregation
and egg-laying decisions.
PMID- 26422513
TI - Mapping the conformational landscape of a dynamic enzyme by multitemperature and
XFEL crystallography.
AB - Determining the interconverting conformations of dynamic proteins in atomic
detail is a major challenge for structural biology. Conformational heterogeneity
in the active site of the dynamic enzyme cyclophilin A (CypA) has been previously
linked to its catalytic function, but the extent to which the different
conformations of these residues are correlated is unclear. Here we compare the
conformational ensembles of CypA by multitemperature synchrotron crystallography
and fixed-target X-ray free-electron laser (XFEL) crystallography. The
diffraction-before-destruction nature of XFEL experiments provides a radiation
damage-free view of the functionally important alternative conformations of CypA,
confirming earlier synchrotron-based results. We monitored the temperature
dependences of these alternative conformations with eight synchrotron datasets
spanning 100-310 K. Multiconformer models show that many alternative
conformations in CypA are populated only at 240 K and above, yet others remain
populated or become populated at 180 K and below. These results point to a
complex evolution of conformational heterogeneity between 180--240 K that
involves both thermal deactivation and solvent-driven arrest of protein motions
in the crystal. The lack of a single shared conformational response to
temperature within the dynamic active-site network provides evidence for a
conformation shuffling model, in which exchange between rotamer states of a large
aromatic ring in the middle of the network shifts the conformational ensemble for
the other residues in the network. Together, our multitemperature analyses and
XFEL data motivate a new generation of temperature- and time-resolved experiments
to structurally characterize the dynamic underpinnings of protein function.
PMID- 26422515
TI - Identification of Clinical and Genetic Parameters Associated with Hidradenitis
Suppurativa in Inflammatory Bowel Disease.
AB - BACKGROUND: Hidradenitis suppurativa (HS) has recently been associated with
inflammatory bowel disease (IBD). The objective of this study is to investigate
the prevalence of HS in IBD and to identify clinical and genetic parameters
associated with HS in IBD. METHODS: A questionnaire, validated for HS, was sent
to 1969 patients suffering from IBD. RESULTS: The prevalence of HS in our IBD
cohort (1260 participating patients) was significantly higher than in the general
population (6.8%-10.6% versus 1%-2%). IBD patients with HS were affected by IBD
significantly earlier and more often treated with anti-TNF-alpha therapy and
surgical resection compared to IBD without HS. Female gender, smoking, a higher
body mass index, and younger age were independent associated parameters for HS.
Within cases allelic association analysis was performed for 59 cases (IBD with
HS) and 293 controls (IBD without HS). We observed 2 promising new associations
in genomic regions harboring ELOVL7 (rsnumber 10057395 P = 7.15 * 10, odds ratio
= 0.4), and in the intergenic region between SULT1B1 and SULT1E1 (rsnumber
2014777 P = 7.48 * 10, odds ratio = 2.3). CONCLUSIONS: HS is present in 6.8% to
10.6% of IBD patients. Co-morbid HS is associated with an early onset of IBD in
which anti-tumor necrosis factor-alpha therapy and surgical resections are often
needed. We identified a suggestive protective association with ELOVL7 and
suggestive risk association with the genes SULT1B1 and SULT1E1 for HS, in the
context of IBD. These genetic associations need further exploration and
replication in additional independent cohorts.
PMID- 26422514
TI - Protein biogenesis machinery is a driver of replicative aging in yeast.
AB - An integrated account of the molecular changes occurring during the process of
cellular aging is crucial towards understanding the underlying mechanisms. Here,
using novel culturing and computational methods as well as latest analytical
techniques, we mapped the proteome and transcriptome during the replicative
lifespan of budding yeast. With age, we found primarily proteins involved in
protein biogenesis to increase relative to their transcript levels. Exploiting
the dynamic nature of our data, we reconstructed high-level directional networks,
where we found the same protein biogenesis-related genes to have the strongest
ability to predict the behavior of other genes in the system. We identified
metabolic shifts and the loss of stoichiometry in protein complexes as being
consequences of aging. We propose a model whereby the uncoupling of protein
levels of biogenesis-related genes from their transcript levels is causal for the
changes occurring in aging yeast. Our model explains why targeting protein
synthesis, or repairing the downstream consequences, can serve as interventions
in aging.
PMID- 26422517
TI - Increasing Patient Activation Could Improve Outcomes for Patients with
Inflammatory Bowel Disease.
AB - Inflammatory bowel disease (IBD) is a complex disease process that often requires
the integration of skills from various health care providers to adequately meet
the needs of patients with IBD. The medical and surgical treatment options for
IBD have become more complicated and are frequently a source of angst for both
the patient and provider. However, it has become more important than ever to
engage patients in navigating the treatment algorithm. Although novel in the IBD
world, the concept of patients' becoming more active and effective managers of
their care has been well studied in other disease processes such as diabetes
mellitus and mental illness. This idea of patient activation refers to a patient
understanding his or her role in the care process and having the skill sets and
self-reliance necessary to manage his or her own health care. Over the past
decade, evidence supporting the role of patient activation in chronic illness has
grown, revealing improved health outcomes, enhanced patient experiences, and
lower overall costs. Patient activation can be measured, and interventions have
been shown to improve levels of activation over time and influence outcomes. A
focus on patient activation is very appropriate for patients with IBD because
this may potentially serve as a tool for IBD providers to not only improve
patient outcomes and experience but also reduce health care costs.
PMID- 26422516
TI - Anti-Tumor Necrosis Factor-alpha Antibody Therapy Management Before and After
Intestinal Surgery for Inflammatory Bowel Disease: A CCFA Position Paper.
AB - Biologic therapy with anti-tumor necrosis factor (TNF)-alpha antibody medications
has become part of the standard of care for medical therapy for patients with
inflammatory bowel disease and may help to avoid surgery in some. However, many
of these patients will still require surgical intervention in the form of bowel
resection and anastomosis or ostomy formation for the treatment of their disease.
Postsurgical studies suggest up to 30% of patients with inflammatory bowel
disease may be on or have used anti-TNF-alpha antibody medications for disease
management preoperatively. Significant controversy exists regarding the potential
deleterious impact of these medications on the outcomes of surgery, specifically
overall and/or infectious complications. In this position statement, we
systematically reviewed the literature regarding the potential risk of anti-TNF
alpha antibody use in the perioperative period, offer recommendations based both
on the best-available evidence and expert opinion on the use and timing of anti
TNF-alpha antibody therapy in the perioperative period, and discuss whether or
not the presence of these medications should lead to an alteration in surgical
technique such as temporary stoma formation.
PMID- 26422518
TI - Pustular Skin Reaction to Tumor Necrosis Factor Alpha Antagonists in Patients
with Inflammatory Bowel Diseases.
PMID- 26422519
TI - Surgery for Crohn's Disease: An Emerging Surgical Specialty.
PMID- 26422520
TI - "Blindly" ADA Dose Escalation to 80 mg Weekly in Crohn's Disease Patients with
LOR: Is It Cost Effective or Not?
PMID- 26422521
TI - Mechanical and Electrical Anisotropy of Few-Layer Black Phosphorus.
AB - We combined reflection difference microscopy, electron transport measurements,
and atomic force microscopy to characterize the mechanical and electrical
anisotropy of few-layer black phosphorus. We were able to identify the lattice
orientations of the two-dimensional material and construct suspended structures
aligned with specific crystal axes. The approach allowed us to probe the
anisotropic mechanical and electrical properties along each lattice axis in
separate measurements. We measured the Young's modulus of few-layer black
phosphorus to be 58.6 +/- 11.7 and 27.2 +/- 4.1 GPa in zigzag and armchair
directions. The breaking stress scaled almost linearly with the Young's modulus
and was measured to be 4.79 +/- 1.43 and 2.31 +/- 0.71 GPa in the two directions.
We have also observed highly anisotropic transport behavior in black phosphorus
and derived the conductance anisotropy to be 63.7%. The test results agreed well
with theoretical predictions. Our work provided very valuable experimental data
and suggested an effective characterization means for future studies on black
phosphorus and anisotropic two-dimensional nanomaterials in general.
PMID- 26422523
TI - Mandibular Overdentures Retained by Two Mini-Implants: A Seven-Year Retention and
Satisfaction Study.
AB - PURPOSE: Patients with atrophic edentulous ridges generally have problems with
retention, therapeutic satisfaction, and comfort with their complete dentures. An
alternative treatment to assist in improving retention and stability involves the
use of mini-implants. The aim of this study was to evaluate the retention of
mandibular overdentures connected to two mini-implants and overall patient
satisfaction with them. MATERIALS AND METHODS: Seven patients with atrophic
mandibular ridges (Type 4D Misch classification), aged 62 to 74 years old were
rehabilitated with complete dentures. In each patient, two mini-implants
measuring 15 or 13 mm in length and 1.8 mm in diameter were placed. After 15
days, overdentures were connected to the mini-implants with O-ring attachments.
In each patient, retention of the overdentures was measured, and a survey of
therapeutic satisfaction before and after connection to the mini-implants was
administered. Prosthesis retention was measured with a digital dynamometer at 1
month, 6 months, and 2, 3, 5, and 7 years after mini-implant placement. Patient
satisfaction was assessed with a survey. Data were analyzed with Student's t-test
(satisfaction survey) and the Friedman test (retention measurements and
satisfaction survey). RESULTS: The initial retention values (0.34 to 0.63 N
without mini-implants) varied significantly (p <= 0.050). These values were less
than the subsequent measurements of 3.92 to 9.64 N, taken after placement of the
mini-implants and connecting them to the dentures. Satisfaction was good to very
good over the 7-year observation period. Mucosa and peri-implant bone showed no
pathological changes. CONCLUSIONS: In this limited sample size clinical study the
results indicated that after connecting mandibular overdentures to two mini
implants, patient satisfaction significantly increased and retention
significantly improved during the 7-year observation period.
PMID- 26422522
TI - Compensatory processing during rule-based category learning in older adults.
AB - Healthy older adults typically perform worse than younger adults at rule-based
category learning, but better than patients with Alzheimer's or Parkinson's
disease. To further investigate aging's effect on rule-based category learning,
we monitored event-related potentials (ERPs) while younger and
neuropsychologically typical older adults performed a visual category-learning
task with a rule-based category structure and trial-by-trial feedback. Using
these procedures, we previously identified ERPs sensitive to categorization
strategy and accuracy in young participants. In addition, previous studies have
demonstrated the importance of neural processing in the prefrontal cortex and the
medial temporal lobe for this task. In this study, older adults showed lower
accuracy and longer response times than younger adults, but there were two
distinct subgroups of older adults. One subgroup showed near-chance performance
throughout the procedure, never categorizing accurately. The other subgroup
reached asymptotic accuracy that was equivalent to that in younger adults,
although they categorized more slowly. These two subgroups were further
distinguished via ERPs. Consistent with the compensation theory of cognitive
aging, older adults who successfully learned showed larger frontal ERPs when
compared with younger adults. Recruitment of prefrontal resources may have
improved performance while slowing response times. Additionally, correlations of
feedback-locked P300 amplitudes with category-learning accuracy differentiated
successful younger and older adults. Overall, the results suggest that the
ability to adapt one's behavior in response to feedback during learning varies
across older individuals, and that the failure of some to adapt their behavior
may reflect inadequate engagement of prefrontal cortex.
PMID- 26422524
TI - Mechanism of Decarboxylation of Pyruvic Acid in the Presence of Hydrogen
Peroxide.
AB - The purpose of this work was to probe the rate and mechanism of rapid
decarboxylation of pyruvic acid in the presence of hydrogen peroxide (H2O2) to
acetic acid and carbon dioxide over the pH range 2-9 at 25 degrees C, utilizing
UV spectrophotometry, high performance liquid chromatography (HPLC), and proton
and carbon nuclear magnetic resonance spectrometry ((1)H, (13)C-NMR). Changes in
UV absorbance at 220 nm were used to determine the kinetics as the reaction was
too fast to follow by HPLC or NMR in much of the pH range. The rate constants for
the reaction were determined in the presence of molar excess of H2O2 resulting in
pseudo first-order kinetics. No buffer catalysis was observed. The calculated
second-order rate constants for the reaction followed a sigmoidal shape with pH
independent regions below pH 3 and above pH 7 but increased between pH 4 and 6.
Between pH 4 and 9, the results were in agreement with a change from rate
determining nucleophilic attack of the deprotonated peroxide species, HOO(-), on
the alpha-carbonyl group followed by rapid decarboxylation at pH values below 6
to rate-determining decarboxylation above pH 7. The addition of H2O2 to ethyl
pyruvate was also characterized.
PMID- 26422525
TI - The minimal clinically important difference for function and strength in patients
undergoing reverse shoulder arthroplasty.
AB - HYPOTHESIS: Despite a statistically significant improvement in functional scores
after receiving a reverse shoulder arthroplasty (RSA) in a cuff-deficient
shoulder, not all patients perceive a minimal clinically important difference
(MCID) in every functional domain of the score. METHODS: This was a prospective
longitudinal study including 60 consecutive patients with a cuff-deficient
shoulder treated with a RSA. The Constant score was recorded before surgery and
at a 1-year follow-up assessment. At the 1-year follow-up, all patients also
filled out a 15-item anchor questionnaire to assess their perception of change in
their overall function, forward elevation, lateral rotation, internal rotation,
and strength to determine the MCID. RESULTS: The mean Constant score was 30.1
(standard deviation, 10.7) before surgery and was 58.4 (standard deviation, 16.2)
at the 1-year follow-up, with statistically significant improvement (P < .001). A
statistically significant improvement was found in the domains of forward
elevation (P < .001), lateral rotation (P < .001), and strength (P < .001) except
for internal rotation (P = .15). The MCID for overall function, forward
elevation, lateral rotation, internal rotation, and strength in the Constant
score increased by 8, 6, 2, 2, and 11.5 points, respectively; only 46.7%, 20%,
50%, 45.8%, and 33.3% of the patients, respectively, exceeded the MCID on each
domain after surgery. CONCLUSIONS: A statistically significant improvement in the
Constant score is expected after receiving an RSA in a cuff-deficient shoulder,
but a considerable number of patients do not reach the MCID in the function and
strength domains. A small improvement in rotation is perceived to be beneficial
by patients, whereas large improvements in forward elevation are required for the
improvement to be perceived to be beneficial.
PMID- 26422526
TI - Radiographic and clinical outcomes of total shoulder arthroplasty with an all
polyethylene pegged bone ingrowth glenoid component: prospective short- to medium
term follow-up.
AB - BACKGROUND: Glenoid components often cause total shoulder arthroplasty failure.
This study examines short-term to midterm radiographic and clinical results of a
hybrid glenoid component with 3 cemented peripheral pegs and a central peg, which
allows biologic fixation with use of native humeral head autograft. METHODS: In 4
years, 80 glenoid components were implanted during primary total shoulder
arthroplasty with at least 2-year follow-up data. Within 12 months, 4 shoulders
were revised and excluded from final analyses. Seven patients did not complete
their questionnaires. Outcomes data included the American Shoulder and Elbow
Surgeons (ASES) questionnaire, Constant score, and satisfaction score. A shoulder
and elbow fellowship-trained surgeon, not involved in the care of these patients,
analyzed radiographs for radiolucent lines, glenoid seating, and radiodensity in
between the flanges of the central peg. RESULTS: Only 1 of 80 shoulders was
revised for aseptic glenoid loosening. At final follow-up, 81.6% had a
radiolucency grade of 0 or 1. Nearly 90% had a glenoid seating grade of A or B.
Grade 2 or 3 bone around the central peg was seen in 88.2%. No statistical
association existed between Walch glenoid types and radiolucency grades, bone
grades around the central peg, perfect radiolucency grade, seating grade, and
grade 3 bone around the central peg. There was significant improvement in mean
ASES score, adjusted ASES pain score, Constant score, and satisfaction score as
well as in forward flexion, abduction, and external rotation. CONCLUSIONS: The
hybrid glenoid can produce stable radiographic and clinical outcomes at short- to
medium-term follow-up.
PMID- 26422527
TI - In vivo three-dimensional elbow biomechanics during forearm rotation.
AB - BACKGROUND: It is unclear how elbow kinematics changes during forearm rotation.
This study investigated in vivo 3-dimensional elbow kinematics during forearm
rotation. METHODS: We studied 12 normal elbows using in vivo 3-dimensional
computed tomography data in maximum forearm supination, neutral, and maximum
pronation with the elbows in extension. We measured the motion of the radius and
ulna relative to the humerus using a markerless bone registration technique and
the contact area of the radiocapitellar joint, proximal radioulnar joint, and
ulnohumeral joint using a proximity mapping method. RESULTS: When the forearm
rotated from the supinated position to the pronated position, the radius showed
significant varus rotation, internal rotation, and extension relative to the
humerus. The center of the radial head significantly translated anteriorly,
proximally, and laterally. The ulna significantly rotated in valgus, and the
deepest point on the sagittal ridge of the trochlear notch translated medially
with forearm pronation. The contact area of the radiocapitellar joint was largest
in pronation. The contact area of the proximal radioulnar joint was largest in
supination. The contact area of the ulnohumeral joint showed no significant
change during forearm rotation. CONCLUSIONS: In pronation, because of the
proximal migration of the radial head, the radiocapitellar joint was most
congruent compared with other positions. The proximal radioulnar joint was most
congruent in supination. The ulnohumeral joint congruency was not affected by
forearm rotation. This study provides useful information for understanding 3
dimensional elbow motion and joint osseous stability related to forearm rotation.
PMID- 26422528
TI - Abrasiveness of high-strength sutures used in rotator cuff surgery: are they all
the same?
AB - BACKGROUND: The suture-tendon interface remains the most common point of failure
in rotator cuff repairs via suture pullout. Several high-strength braided sutures
are available for rotator cuff surgery and are more abrasive than monofilaments.
However, a comparison of these sutures has not been performed in a tissue model.
METHODS: Ninety infraspinatus sheep tendons were randomized among 9 groups of
sutures (n = 10), including FiberWire (Arthrex, Naples, FL, USA), Collagen Coated
FiberWire (Arthrex), Orthocord (DePuy Mitek, Raynham, MA, USA), MaxBraid (Biomet,
Warsaw, IN, USA), Force Fiber (Teleflex, Research Triangle Park, NC, USA),
ULTRABRAID (Smith & Nephew, Memphis, TN, USA), Phantom Fiber BioFiber (Tornier,
Bloomington, MN, USA), and Ti-Cron (Syneture, Mansfield, MA), with Surgipro
(Syneture) monofilament as a control. Each suture was cycled 50 times through the
tendon, which was fixed to a mechanical testing system under a constant load in
saline solution. The distance cut through the tendon was measured and divided by
the distance of suture sliding to determine displacement (mm/cm). Twist angle and
picks per inch of each suture were measured using digital photography. One-way
analysis of variance was used to compare the displacement and twist angle between
sutures. RESULTS: Collagen Coated FiberWire was the most abrasive of the high
strength sutures. Four of the sutures (Collagen Coated FiberWire, Phantom Fiber
BioFiber, FiberWire, Ti-Cron) had a mean displacement rate greater than 0.150
mm/cm. The remainder of the sutures had a mean displacement rate less than 0.050
mm/cm (Orthocord, Force Fiber, MaxBraid, ULTRABRAID). The difference in the
displacement rates between these 2 groups was significant (P < .0001) and was
related to both the twist angle and the picks per inch. CONCLUSION: Significant
differences in suture abrasiveness were identified among high-strength braided
sutures and correlated with lower twist angle and lower picks per inch.
PMID- 26422530
TI - Selective, Spontaneous One-Way Oil-Transport Fabrics and Their Novel Use for
Gauging Liquid Surface Tension.
AB - Thin porous materials that can spontaneously transport oil fluids just in a
single direction have great potential for making energy-saving functional
membranes. However, there is little data for the preparation and functionalities
of this smart material. Here, we report a novel method to prepare one-way oil
transport fabrics and their application in detecting liquid surface tension. This
functional fabric was prepared by a two-step coating process to apply flowerlike
ZnO nanorods, fluorinated decyl polyhedral oligomeric silsesquioxanes, and
hydrolyzed fluorinated alkylsilane on a fabric substrate. Upon one-sided UV
irradiation, the coated fabric shows a one-way transport feature that allows oil
fluid transport automatically from the unirradiated side to the UV-irradiated
surface, but it stops fluid transport in the opposite direction. The fabric still
maintains high superhydrophobicity after UV treatment. The one-way fluid
transport takes place only for the oil fluids with a specific surface tension
value, and the fluid selectivity is dependent on the UV treatment time. Changing
the UV irradiation time from 6 to 30 h broadened the one-way transport for fluids
with surface tension from around 22.3 mN/m to a range of 22.3-56.7 mN/m. We
further proved that this selective one-way oil transport can be used to estimate
the surface tension of a liquid simply by observing its transport feature on a
series of fabrics with different one-way oil-transport selectivities. To our
knowledge, this is the first example to use one-way fluid-transport materials for
testing the liquid surface tension. It may open up further theoretical studies
and the development of novel fluid sensors.
PMID- 26422529
TI - Compensatory hypertrophy of the teres minor muscle after large rotator cuff tear
model in adult male rat.
AB - BACKGROUND: Rotator cuff tear (RCT) is a common musculoskeletal disorder in the
elderly. The large RCT is often irreparable due to the retraction and
degeneration of the rotator cuff muscle. The integrity of the teres minor (TM)
muscle is thought to affect postoperative functional recovery in some surgical
treatments. Hypertrophy of the TM is found in some patients with large RCTs;
however, the process underlying this hypertrophy is still unclear. The objective
of this study was to determine if compensatory hypertrophy of the TM muscle
occurs in a large RCT rat model. METHODS: Twelve Wistar rats underwent
transection of the suprascapular nerve and the supraspinatus and infraspinatus
tendons in the left shoulder. The rats were euthanized 4 weeks after the surgery,
and the cuff muscles were collected and weighed. The cross-sectional area and the
involvement of Akt/mammalian target of rapamycin (mTOR) signaling were examined
in the remaining TM muscle. RESULTS: The weight and cross-sectional area of the
TM muscle was higher in the operated-on side than in the control side. The
phosphorylated Akt/Akt protein ratio was not significantly different between
these sides. The phosphorylated-mTOR/mTOR protein ratio was significantly higher
on the operated-on side. CONCLUSION: Transection of the suprascapular nerve and
the supraspinatus and infraspinatus tendons activates mTOR signaling in the TM
muscle, which results in muscle hypertrophy. The Akt-signaling pathway may not be
involved in this process. Nevertheless, activation of mTOR signaling in the TM
muscle after RCT may be an effective therapeutic target of a large RCT.
PMID- 26422531
TI - Global Quantitative Techniques for Positron Emission Tomographic Assessment of
Disease Activity in Cutaneous T-Cell Lymphoma and Response to Treatment.
PMID- 26422532
TI - Risk of multiple myeloma in a case-spouse study.
AB - This study examined lifestyle, occupation, medical history and medication use
with multiple myeloma risk in a case-spouse study (481 patients, 351 spouses).
Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using
logistic regression. Compared to spouse controls, cases were more likely to have
a family history of multiple myeloma (OR = 2.8, 95% CI = 1.2-6.4) and smoked
cigarettes (OR = 1.7, 95% CI = 1.2-2.5), but less likely to have consumed alcohol
(OR = 0.6, 95% CI = 0.4-0.9). Nurse/health practitioners (OR = 2.8, 95% CI = 1.3
6.2) and production workers (OR = 3.7, 95% CI = 1.0-13.7) had significantly
increased risks; and some occupations linked to diesel exhaust had elevated, but
non-significant, risks. History of herpes simplex (OR = 1.7, 95% CI = 1.2-2.4),
shingles (OR = 1.7, 95% CI = 1.1-2.7), sexually transmitted diseases (OR = 2.0,
95% CI = 1.0-3.7) and medication allergies (OR = 1.7, 95% CI = 1.2-2.4) were
associated with higher risks. Use of angiotensin-converting enzyme inhibitors,
anti-convulsants, antidepressants, statins and diuretics were associated with
reduced risks. The results are consistent with previous population-based studies
and support the utility of patient databanks and spouse controls as a resource in
epidemiologic research.
PMID- 26422533
TI - Characteristics and Clinical Course of STEMI Patients who Received no Reperfusion
in the Australia and New Zealand SNAPSHOT ACS Registry.
AB - BACKGROUND: Cohort studies of STEMI patients have reported that over 30% receive
no reperfusion. Barriers to greater use of reperfusion in STEMI patients require
further elucidation. METHODS: We collected data on STEMI patients with no
reperfusion as part of the SNAPSHOT ACS Registry, which recruited consecutive ACS
patients in 478 hospitals throughout Australia and New Zealand during 14-27 May
2012. RESULTS: Of 4387 patients enrolled, 419 were diagnosed with STEMI. Primary
PCI (PPCI) was performed in 160 (38.2%), fibrinolysis was used in 105 (25.1%),
and 154 (36.7%) had no reperfusion. Patients with no reperfusion had a mean age
of 70.3+/-15.0 years compared with 63.1+/-13.5 in the reperfusion group
(p<0.0001). There were more females in the no reperfusion group (37.1% v 23.0%
p=0.002) and they were significantly more likely to have prior PCI or CABG, heart
failure, atrial fibrillation, chronic kidney disease and other vascular disease,
and to be nursing home residents (all p<0.05). Patients without reperfusion had a
significantly higher mortality in hospital (11.7% v 4.9%, p=0.011). In 370
patients who presented within 12hours, 28 had early angiography without PCI,
which was considered an attempt at reperfusion. Therefore reperfusion was
attempted in 293 of 370 eligible patients (79.2%). CONCLUSION: Of consecutive
STEMI patients, 36.7% did not receive any reperfusion and they had a higher risk
of death in hospital. In eligible patients, reperfusion was attempted in 79.2%.
National strategies to encourage earlier medical contact and greater use of
reperfusion in eligible patients may lead to better outcomes.
PMID- 26422534
TI - Retrograde Type A Aortic Dissection Treated with Continuous Perfusion "Branch
First" Aortic Arch Replacement Technique.
AB - The development of thoracic endovascular aortic repair in recent years has
revolutionised the way aortic disease is treated. However, there are potential
complications associated with this which can be life threatening and pose a
difficult challenge to manage. We present a case of retrograde ascending aortic
dissection complicating thoracic endovascular aortic repair, and its repair using
a technique of continuous perfusion "branch-first" aortic arch replacement. We
discuss the complication of retrograde ascending aortic dissection and the issues
that affect its surgical management.
PMID- 26422535
TI - Association of Sleep Duration with the Morbidity and Mortality of Coronary Artery
Disease: A Meta-analysis of Prospective Studies.
AB - PURPOSE: Insufficient and excessive sleep duration have become increasingly
common in modern society. Published literatures report controversial results
about the association of sleep duration with coronary artery disease (CAD).
METHODS: A comprehensive search was performed to identify related prospective
studies providing quantitative estimates between sleep duration and CAD. Meta
analysis was applied to calculate the combined relative risks (RRs) with 95%
confidence intervals (CI) for sleep with morbidity and mortality of CAD. The risk
of bias was assessed by the Egger regression asymmetry test. RESULTS: Fifteen
studies conformed to the criteria. Compared with normal sleep duration, the
pooled RRs (95%CI) of short sleep duration were 1.10(1.04-1.17) and 1.25(1.06
1.47) for the morbidity and mortality of CAD, and the pooled RRs (95%CI) of long
sleep duration were 1.03(0.92-1.16) and 1.26(1.11-1.42) for the morbidity and
mortality of CAD, respectively. The effect of short and long sleep duration on
mortality of CAD were always significantly greater than the morbidity of CAD.
CONCLUSIONS: Short sleep duration was associated with higher morbidity of CAD,
and short sleepers and long sleepers had higher risk for CAD mortality. Keeping
normal sleep duration is an appropriate recommendation to prevent and control
CAD.
PMID- 26422536
TI - Particle- and Gaseous Emissions from an LNG Powered Ship.
AB - Measurements of particle number and mass concentrations and number size
distribution of particles from a ship running on liquefied natural gas (LNG) were
made on-board a ship with dual-fuel engines installed. Today there is a large
interest in LNG as a marine fuel, as a means to comply with sulfur and NOX
regulations. Particles were studied in a wide size range together with
measurements of other exhaust gases under different engine loads and different
mixtures of LNG and marine gas oil. Results from these measurements show that
emissions of particles, NOX, and CO2 are considerably lower for LNG compared to
present marine fuel oils. Emitted particles were mainly of volatile character and
mainly had diameters below 50 nm. Number size distribution for LNG showed a
distinct peak at 9-10 nm and a part of a peak at diameter 6 nm and below.
Emissions of total hydrocarbons and carbon monoxide are higher for LNG compared
to present marine fuel oils, which points to the importance of considering the
methane slip from combustion of LNG.
PMID- 26422538
TI - Ageism in Health Care?
PMID- 26422539
TI - Advances in the Molecular Profiling of Tumor Tissue.
PMID- 26422540
TI - Mutation Profiling of Clinically Advanced Cancers Using Next-Generation
Sequencing for Targeted Therapy: A Lifespan Experience.
AB - The application of modern molecular tests such as next-generation sequencing
(NGS) to human malignancies has led to better understanding of tumor biology and
the design of targeted molecular therapies. In the research setting, important
genomic alterations in tumors have been discovered with potential therapeutic
implications but data regarding the impact of this technology in a real world
oncology practice is limited. As a result, we decided to review the results of
NGS in 144 advanced-stage cancer patients referred to the oncology practices of
Lifespan-affiliated centers in Rhode Island. Most cancers revealed genomic
alterations in genes commonly mutated in cancer. However, several unexpected
genomic alterations were discovered in certain cancers with potential therapeutic
intervention. Most cancers contained "actionable" genomic alterations despite
being of advanced stage. Our experience demonstrates that application of NGS in
the clinical setting contributes both to increasing the therapeutic armamentarium
as well as our understanding of tumor biology.
PMID- 26422541
TI - Updates in Tumor Profiling in Gastrointestinal Cancers.
AB - In the last decade there has been a focus on biomarkers that play a critical role
in understanding molecular and cellular mechanisms which drive tumor initiation,
maintenance and progression of cancers. Characterization of genomes by next
generation sequencing (NGS) has permitted significant advances in
gastrointestinal cancer care. These discoveries have fueled the development of
novel therapeutics and have laid the groundwork for the development of new
treatment strategies. Work in colorectal cancer (CRC) has been in the forefront
of these advances. With the continued development of NGS technology and the
positive clinical experience in CRC, genome work has begun in esophagogastric,
pancreatic, and hepatocellular carcinomas as well.
PMID- 26422542
TI - NSCLC: An Update of Driver Mutations, Their Role in Pathogenesis and Clinical
Significance.
AB - Lung cancer is the most common malignancy in the US and causes the most cancer
related deaths. Non-small-cell lung carcinoma (NSCLC) accounts for the majority
of cases. NSCLC historically was considered one entity, reflected by platinum
based therapy as the standard of care; however, with the discovery of EGFR
mutations and ALK rearrangements, the landscape of treatment has become more
personalized reflecting genomic heterogeneity. The molecular basis for tumor
genesis was recognized and became a new method of classification. The
availability of tumor sequencing and testing for these mutations is also becoming
more accessible outside of major academic institutions. Targeted therapies offer
alternatives to dangerous cytotoxic chemotherapy with equal or better efficacy.
With these changes, driver mutations will play an increasing role in the
diagnosis and treatment of NSCLC. In this review we will examine the
characteristics of several NSCLC driver mutations and gene rearrangements and
emerging data on therapies directed against them.
PMID- 26422543
TI - Primary Care Physicians' Use of Electronic Health Records in Rhode Island: 2009
2014.
AB - We used data from the mandatory statewide Rhode Island (RI) Health Information
Technology (HIT) Survey to characterize office-based PCPs' adoption and use of
EHRs from 2009-2014. We found accelerated adoption of EHRs in the five years
since state and federal incentive programs began targeting PCPs' adoption of HIT.
There was room for improvement, however; for example, when asked to indicate the
proportion of patients with whom they used various functionalities, only 13.4% of
office-based PCPs said they "almost always" communicated with patients using
secure messaging and 22.3% "almost always" used secure clinical messaging with
outside providers. Results suggest uneven use of EHR functionalities, with low
rates and slower uptake in some areas. These findings highlight opportunities to
increase use of functionalities related to improved patient care and quality
based payment models.
PMID- 26422544
TI - Recurrent Mixed Cryoglobulinemia (MCS): A Case Report and Literature Review.
AB - We report a case of recurrent mixed type II cryoglobulinemia with difficult
diagnosis and treatment dilemma and uncertain prognosis in view of limited
studies. A 60-year-old male with history of essential mixed cryoglobulinemia 12
years ago treated successfully with six months of cyclophosphamide and prednisone
presented with bilateral lower extremity pupuric rash and swelling. He was found
to have proteinuria, hematuria, RBC casts, low serum complement levels, and acute
kidney injury (AKI). Initial therapy with methylprednisone and oral
cyclophosphamide was ineffective (patient developed respiratory failure due to
alveolar hemorrhage). Additional labs revealed positive type II cryoglobulins,
high free Kappa/Lambda, UPEP with minimal urine protein, SPEP with marked
hypogammaglobulinemia, and negative tests for HIV, HCV, ANA, and ANCA. More
aggressive therapy with daily plasmapheresis and rituximab was instituted with
very good clinical response. He achieved clinical remission but developed another
flare 8 months later. Kidney biopsy showed membranoproliferatve
glomerulonephritis with cryoglobulin deposits. Flow cytometry and biopsy of bone
marrow was consistent with lymphoplasmacytic lymphoma. His diagnosis was
eventually confirmed and responded clinically to another course of rituximab and
plasmapheresis, but prognosis is yet to be seen.
PMID- 26422545
TI - Understanding the Disparities of Citizen Health Preparedness - Can Providers Help
Close the Gaps?
PMID- 26422546
TI - van der Waals force-induced loading of proangiogenic nanoparticles on
microbubbles for enhanced neovascularization.
AB - Nanoparticles emerged as carriers of promising diagnostic and therapeutic
molecules due to their unique size, injectability, and potential to sustainably
release molecular cargos. However, with local injection of particles into target
tissue, the significant particle loss caused by external biomechanical forces is
a great challenge yet to be resolved to date. We hypothesized that nanoparticles
associated with tissue-adherent microbubbles in the form of core-shell particles
due to van der Waals attractive forces would stably remain on an implanted site
and significantly increase therapeutic efficacy of drug cargos. To examine this
hypothesis, we used 100 nm diameter nanoparticles made of poly(lactide-co
glycolic acid) (PLGA) as a model nanoparticle and 50 MUm diameter microbubbles
made of poly(2-hydroxyethyl aspartamide) (PHEA) grafted with octadecyl chains,
PHEA-g-C18, as a model microbubble. Simple mixing of PLGA nanoparticles and PHEA
g-C18 microbubbles resulted in the core-shell particles. Following implantation,
the PHEA-g-C18 microbubbles acted as glue to minimize the displacement of PLGA
nanoparticles, because of the association between the octadecyl chains on PHEA-g
C18 and the epithelium of the tissue. As a consequence, the core-shell particles
prepared with Angiopoietin-1 (Ang1)-encapsulated PLGA nanoparticles significantly
promoted vascularization in the implanted tissue. Overall, the results of this
study provide a simple but advanced strategy for improving therapeutic efficacy
of drug-carrying nanoparticles without altering their surface chemistry and
potential.
PMID- 26422547
TI - In memoriam: A tribute to the work and lives of Ron Selvester and Rory Childers.
AB - At the April, 2015 International Society for Computerized Electrocardiology
(ISCE) Annual Conference in San Jose, CA, a special session entitled Remembering
Ron & Rory was held to pay tribute to the extraordinary work and lives of two
experts in electrocardiology. The session was well attended by conference
attendees, Childers' family members and friends, and additional colleagues who
traveled to San Jose solely to participate in this session. The purpose of the
present paper is to document the spirit of this special session as faithfully as
possible using the words of the session speakers.
PMID- 26422548
TI - Correlates of health-related quality of life in Thai patients with alcohol
dependence.
AB - This study aimed to examine the correlates of health related quality of life in
Thai patients with alcohol dependence. The amount of alcohol intake was
calculated by timeline followback chart and the health related quality of life
was determined by Short Form-36 Health Survey. The means of the Short Form-36
Physical Component and Mental Component Summary were 67.43 (18.74) and 64.45
(20.90), respectively. Stepwise linear regression models showed the number of
heavy drinking days was significantly correlated with the Physical Component
Summary and Mental Component Summary. Such moderate correlations suggest that
drinking and health related quality of life measures might tap different aspects
of alcohol outcomes and should be concurrently administered.
PMID- 26422549
TI - Can electrodynamic interaction between a molecule and metal dominate a continuum
background in surface-enhanced Raman scattering?
AB - A continuum background is always coincident with the Raman spectrum enhanced by
metallic nanostructures and still remains elusive. Not only does it constitute a
stymied mystery in the origin per se, but also it reduces the useful quantifiable
range of detection based on surface-enhanced Raman scattering (SERS). We examined
theoretically near-field molecule-metal interaction to reveal its contribution to
the SERS background. The results show that the spectral broadening of
fluorescence and Raman scattering due to a nearby metal object is insignificant
compared with experimental findings. This study abnegates the role of near-field
interaction in the SERS continuum background and elucidates the microscopic
molecule-metal electromagnetic interaction, despite being unable to pinpoint the
primary source of the SERS background.
PMID- 26422550
TI - Effect of kinesiotaping, non-elastic taping and bracing on segmental foot
kinematics during drop landing in healthy subjects and subjects with chronic
ankle instability.
AB - OBJECTIVE: To evaluate the effects of kinesiotape, non-elastic tape, and soft
brace on segmental foot kinematics during drop landing in subjects with chronic
ankle instability and healthy subjects. DESIGN: Controlled study with repeated
measurements. SETTING: Three-dimensional motion analysis laboratory.
PARTICIPANTS: Twenty participants with chronic ankle instability and 20 healthy
subjects. INTERVENTIONS: The subjects performed drop landings with 17
retroreflective markers on the foot and lower leg in four conditions: barefoot,
with kinesiotape, with non-elastic tape and with a soft brace. MAIN OUTCOME
MEASURES: Ranges of motion of foot segments using a foot measurement method.
RESULTS: In participants with chronic ankle instability, midfoot movement in the
frontal plane (inclination of the medial arch) was reduced significantly by non
elastic taping, but kinesiotaping and bracing had no effect. In healthy subjects,
both non-elastic taping and bracing reduced that movement. In both groups, non
elastic taping and bracing reduced rearfoot excursion in inversion/eversion
significantly, which indicates a stabilisation effect. No such effect was found
with kinesiotaping. All three methods reduced maximum plantar flexion
significantly. CONCLUSIONS: Non-elastic taping stabilised the midfoot best in
patients with chronic ankle instability, while kinesiotaping did not influence
foot kinematics other than to stabilise the rearfoot in the sagittal plane.
CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01810471.
PMID- 26422552
TI - How Can Relation Between Pericardial Effusion and Acute Kidney Injury Be
Explained?
PMID- 26422551
TI - Musculoskeletal pain, depression, and stress among Latino manual laborers in
North Carolina.
AB - The jobs of Latino manual laborers place their mental and physical health at
risk. This study evaluates the associations among musculoskeletal pain, mental
health, and work organization in Latino manual laborers. Farmworkers and
nonfarmworkers (n = 189) in North Carolina were interviewed for self-reported
musculoskeletal pain, depressive symptoms, stress, work safety climate, and
precarious job status. More nonfarmworkers than farmworkers had neck and shoulder
pain, but they did not differ in other areas of musculoskeletal pain. Depressive
symptoms had a significant association with neck and shoulder pain (p < .05).
Precariousness had a significant association with back pain (p < .05). Farmworker
participants had H-2A visas and were afforded some protection compared to
nonfarmworker manual workers. Research is needed to improve policy that relieves
pain and improves mental health for all Latino manual workers.
PMID- 26422553
TI - Previously Complicated Nuss Procedure Does Not Preclude Blind Removal of the Bar.
AB - BACKGROUND: Nuss procedure has become the procedure of choice for well-selected
patients with pectus excavatum. Perioperative complications may pose difficulty
during the subsequent bar removal due to adhesions and tissue plane disruptions
during the initial surgery and repair. This report describes bar removal
experience in patients whose Nuss procedures were complicated by cardiac injury,
pericardial breach, and lung parenchyma/diaphragm injury during the initial
procedure. METHODS: A total of 529 patients who underwent Nuss procedure between
2007 and 2014 were recorded in a prospective database. Twenty patients with
complications (cardiac injury [n = 1], pericardial breach [n = 3], and lung
parenchyma/diaphragm injury [n = 16]) were identified. All bars were removed via
subcutaneous tissue dissection, without intrathoracic visualization. RESULTS:
Average duration of bars was 36 months (+/-16 months). All bar removal procedures
were completed without any need for extra interventions with negligible blood
loss. Eighteen patients were able to be discharged within 2 postoperative days.
CONCLUSION: Blind bar removal in patients with previously complicated Nuss
procedure seems safe and no other interventions (videothoracoscopy, subxiphoid
incision, etc.) during bar removal seem to be necessary.
PMID- 26422554
TI - Reply by the Authors of the Original Article.
PMID- 26422555
TI - Doppler Systolic Signal Void in Hypertrophic Cardiomyopathy: Apical Aneurysm and
Severe Obstruction without Elevated Intraventricular Velocities.
AB - BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), akinetic apical
aneurysms are associated with ventricular tachycardia, heart failure, apical
thrombus, and mortality. The cause of apical aneurysms remains unresolved, and
there is controversy about prevalence and significance of mid-left ventricular
(LV) obstruction, often present in these patients. The aim of this study was to
test the hypothesis that low velocities in patients with aneurysms are due to
near complete cessation of mid-LV flow, characteristically marked by a Doppler
signal void. METHODS: This was a retrospective analysis of 39 patients with HCM
with segmental hypertrophy of the mid left ventricle and complete systolic
emptying at the mid-LV level. The severity of dynamic obstruction was evaluated
by measuring the time during which cross-sectional mid-LV cavity area was <1
cm(2). Presence or absence of an LV Doppler midsystolic signal void was
determined. RESULTS: Akinetic apical aneurysms were present in 21 patients. The
duration of two-dimensional mid-LV short-axis complete emptying was longer in
patients with akinetic apical aneurysms (194 +/- 45 vs 148 +/- 63 msec, P =
.013), nearly 50% of systole. Midsystolic signal voids were seen only in patients
with akinetic apical aneurysms (P < .001), present in 86%. In patients with
akinetic aneurysms, there was a strong correlation between the duration of the
systolic signal void and the proportion of systole with complete emptying < 1
cm(2) (r = 0.704; P = .001). Complete emptying < 1 cm(2) for >= 38% of systole
was associated with akinetic aneurysm (odds ratio, 9.35; P < .004). CONCLUSION:
Patients with akinetic apical aneurysm HCM have near complete cessation of flow
across severe dynamic mid-LV obstruction for nearly 50% of systole. This explains
how the adverse effects of obstruction may occur without high velocities on
echocardiography.
PMID- 26422557
TI - The presence of low-count chronic lymphocytic leukemia-like monoclonal B
lymphocytosis in patients with Ph-myeloproliferative neoplasms: A random event or
a shared causal pathobiology?
PMID- 26422556
TI - Reconstitution of lymphocyte subpopulations after hematopoietic stem cell
transplantation: comparison of hematologic malignancies and donor types in event
free patients.
AB - The reconstitution of different immunocyte subsets after hematopoietic stem cell
transplantation (HSCT), follows different timelines. We prospectively
investigated changes in lymphocyte subsets after HSCT and their associations with
primary diagnosis, conditioning regimen, and HSCT type in event-free patients. A
total of 95 patients (48 with acute myeloid leukemia, 22 with acute lymphoid
leukemia, and 25 with myelodysplastic syndrome) who underwent allogeneic HSCT (34
sibling matched, 37 unrelated matched, and 24 haploidentical HSCT) but did not
experience any events such as relapse or death were enrolled in this study.
Lymphocyte subpopulations (T cells, helper/inducer T cells, cytotoxic/suppressor
T cells, memory T cells, regulatory T cells, natural killer (NK) cells, NK-T
cells, and B cells) were quantified by flow cytometry of peripheral blood from
recipients 7 days before and 1, 2, 3, 6, and 12 months after HSCT. Leukocyte
counts recovered within 1 month after HSCT. However, the number of T and B
lymphocytes recovered at 2 months after HSCT. NK cell counts recovered shortly
after haploidentical HSCT. However, T lymphocytes and their subpopulations showed
delayed recovery after haploidentical HSCT. Lymphocyte subsets showed different
sequential patterns according to HSCT type but no differences were seen according
to primary diagnosis or conditioning regimen.
PMID- 26422558
TI - Flow cytometry in immunoglobulin light chain amyloidosis: Short review.
AB - Flow cytometry (FCM) has found its application in clinical diagnosis and
evaluation of monoclonal gammopathies (MG). Although, research has been mainly
focused on multiple myeloma (MM), nowadays FCM becomes to be potential tool in
the field of AL amyloidosis. Clonal plasma cells identification and specific
phenotype profile detection is important for diagnosis, monitoring and prognosis
of AL amyloidosis. Therefore, FCM could be a perspective method for study not
only MM but also AL amyloidosis. This review provides an overview and
possibilities of FCM application in AL amyloidosis.
PMID- 26422559
TI - High-Quality InAsSb Nanowires Grown by Catalyst-Free Selective-Area Metal-Organic
Chemical Vapor Deposition.
AB - We report on the first demonstration of InAs1-xSbx nanowires grown by catalyst
free selective-area metal-organic chemical vapor deposition (SA-MOCVD). Antimony
composition as high as 15 % is achieved, with strong photoluminescence at all
compositions. The quality of the material is assessed by comparing the
photoluminescence (PL) peak full-width at half-max (fwhm) of the nanowires to
that of epitaxially grown InAsSb thin films on InAs. We find that the fwhm of the
nanowires is only a few meV broader than epitaxial films, and a similar trend of
relatively constant fwhm for increasing antimony composition is observed.
Furthermore, the PL peak energy shows a strong dependence on temperature,
suggesting wave-vector conserving transitions are responsible for the observed PL
in spite of lattice mismatched growth on InAs substrate. This study shows that
high-quality InAsSb nanowires can be grown by SA-MOCVD on lattice mismatched
substrate, resulting in material suitable for infrared detectors and high
performance nanoelectronic devices.
PMID- 26422560
TI - Unveiling the Atomic-Level Determinants of Acylase-Ligand Complexes: An
Experimental and Computational Study.
AB - The industrial production of higher-generation semisynthetic cephalosporins
starts from 7-aminocephalosporanic acid (7-ACA), which is obtained by deacylation
of the naturally occurring antibiotic cephalosporin C (CephC). The enzymatic
process in which CephC is directly converted into 7-ACA by a cephalosporin C
acylase has attracted industrial interest because of the prospects of simplifying
the process and reducing costs. We recently enhanced the catalytic efficiency on
CephC of a glutaryl acylase from Pseudomonas N176 (named VAC) by a protein
engineering approach and solved the crystal structures of wild-type VAC and the
H57betaS-H70betaS VAC double variant. In the present work, experimental
measurements on several CephC derivatives and six VAC variants were carried out,
and the binding of ligands into the VAC active site was investigated at an
atomistic level by means of molecular docking and molecular dynamics simulations
and analyzed on the basis of the molecular geometry of encounter complex
formation and protein-ligand potential of mean force profiles. The observed
significant correlation between the experimental data and estimated binding
energies highlights the predictive power of our computational method to identify
the ligand binding mode. The present experimental-computational study is well
suited both to provide deep insight into the reaction mechanism of cephalosporin
C acylase and to improve the efficiency of the corresponding industrial process.
PMID- 26422561
TI - Sarcoidosis and risk of venous thromboembolism: A systematic review and meta
analysis.
AB - BACKGROUND: Several chronic inflammatory disorders, such as rheumatoid arthritis,
inflammatory myositis and systemic lupus erythematosus, have been linked to an
increased risk of venous thromboembolism (VTE). However, the data on sarcoidosis
is unclear. OBJECTIVES: To evaluate the risk of VTE among patients with
sarcoidosis. METHODS: We conducted a systematic review and meta-analysis of
observational studies that reported odds ratio, relative risk, hazard ratio or
standardized incidence ratio comparing risk of VTE in patients with sarcoidosis
versus non-sarcoidosis participants. Estimated effects were extracted from each
study and were pooled together using the random-effect, generic inverse variance
method of DerSimonian and Laird. RESULT: Out of 772 potentially relevant
articles, three eligible studies were identified and included in the data
analysis. The pooled risk ratio of VTE in patients with sarcoidosis was 1.42 (95%
CI, 1.12-1.79). The statistical heterogeneity of this study was moderate with an
I2 of 72%. CONCLUSION: Our study demonstrated a statistically significant
increased VTE risk among patients with sarcoidosis.
PMID- 26422562
TI - Diagnostic efficacy of ultrasound-guided core-needle biopsy of peripheral lymph
nodes in sarcoidosis.
AB - BACKGROUND: Core-needle biopsy guided by ultrasound can be performed for
investigating peripheral lymph node (PLN). The aim of this study was to determine
the efficacy of this technique in sarcoidosis. METHODS: Retrospective review of
files of all patients in the database of the radiology department of Avicenne
university hospital who underwent PLN biopsies guided by ultrasound from January
2008 to June 2011 (n=292). Cases with either granulomas at histology with the
procedure or with a final diagnosis of sarcoidosis were included in the study.
RESULTS: The histological specimens were adequate in 282 out of 292 cases (96%)
showing non-caseating granulomas in 22 cases (n=20 patients with a final
diagnosis of sarcoidosis and n=2 patients with tuberculosis). After reviewing
clinical files of the 282 patient, 22 were confirmed to have sarcoidosis, at
initial presentation (n=19) or later during flare-up or relapse (n=3) with only 2
patients having no granuloma on PLN biopsy. PLN were palpable in 18 cases and
only detected by (18F)FDG-PET/CT showing increased PLN uptake in 4 cases. The
sensitivity and specificity of adequate biopsy were 91 and 99% and the positive
and negative predictive values were 91 and 99%, respectively. CONCLUSION: Core
needle biopsy guided by ultrasound has a high efficacy for evidencing granulomas
in sarcoidosis patients with PLN involvement either clinically palpable or in the
presence of (18F)FDG-PET/CT uptake.
PMID- 26422563
TI - Common chitotriosidase duplication gene polymorphism and clinical outcome status
in sarcoidosis.
AB - BACKGROUND: Chitotriosidase has been found to be useful as a sarcoidosis
biomarker. In patients with better outcome lower values were observed. Some
subjects have 24-base pair duplication in the chitotriosidase gene (CHIT1) that
results in the production of inactive enzyme. This might influence the outcome of
sarcoidosis and account for described observations. OBJECTIVES: The aim of this
study was to correlate common CHIT1 duplication polymorphism and clinical outcome
status in sarcoidosis (COS). METHODS: This retrospective study comprised 180
patients with sarcoidosis. COS at 3, 5 and 10 years was determined and correlated
with CHIT1 24-base pair duplication polymorphism. CHIT1 genotyping was done by
the PCR method. RESULTS: There was no significant correlation between CHIT1 24
base pair duplication polymorphism and COS at 3, 5 or 10 years but a subgroup
analysis showed higher frequency of patients with Loefgren's syndrome (50% vs.
17.1%) and better COS in CHIT1 24-base pair duplication homozygotes vs. all other
subjects in major COS groups (no, minimal and persistent disease) at 3 years
(p=0.025) and borderline significant at 5 years (p = 0.090). CONCLUSIONS: In this
study no correlation between CHIT1 24-base pair duplication polymorphism and COS
was shown, but possible protective role of homozygous condition for CHIT1 24-base
pair duplication polymorphism is suggested.
PMID- 26422564
TI - Sarcoid in cancer patients: clinical characteristics and associated disease
status.
AB - BACKGROUND: The increased risk of cancer in patients with sarcoidosis is well
established, but there is little information regarding sarcoid diagnosed during
or following cancer. The purpose of this study is to describe and analyze the
disease status and events associated with the diagnosis of sarcoid in cancer
patients. METHODS: At a large cancer center, we identified 64 patients with a
pathologic diagnosis of sarcoid-like granuloma during or following a diagnosis of
malignancy. Pathology specimens were re-examined by experts, and clinical and
imaging information were reviewed. Disease-related events including recurrence,
progression, death, and second malignancy were analyzed. RESULTS: The most common
primary malignancies were breast (17%), lymphoma (16%), lung (13%), and
testicular cancer (11%). Thirty-six out of 64 patients (56%) were diagnosed with
sarcoid within 10 months of their primary malignancy, whereas 28 (44%) were
diagnosed with sarcoid in follow-up, including 15/28 without evidence of disease,
6 with associated diagnosis of recurrence, 5 with associated diagnosis of second
malignancy, 1 with stable disease, and 1 with progressive disease. Sarcoid biopsy
sites included mediastinal nodes (59%), hilar nodes (13%), lung (30%), and other
nodes (17%), and the reason for biopsy was usually abnormal imaging (66%).
Sarcoid and tumor were co-localized in 34%. Including long-term follow-up events,
sarcoid was present in association with 10 of 19 recurrences (53%) and 8 of 12
second malignancies (67%). CONCLUSION: While sarcoid often presents at initial
diagnosis or staging of cancer, in a significant number of patients, it appears
in association with recurrence or second malignancy.
PMID- 26422565
TI - Heart transplantation for advanced heart failure due to cardiac sarcoidosis.
AB - BACKGROUND: Selected patients with cardiac sarcoidosis undergo heart
transplantation, but outcomes may be adversely affected by recurrent cardiac
sarcoidosis or progressive extra-cardiac sarcoidosis. OBJECTIVES: We present our
single-center experience of patients with cardiac sarcoidosis who underwent heart
transplantation. METHODS: Consecutive patients that underwent heart
transplantation between 1990 and 2012 were assessed. Cardiac sarcoidosis was
defined by the presence of multiple non-caseating epithelioid cell granulomata in
the explanted heart. Baseline characteristics and clinical outcomes were compared
with a control group without cardiac sarcoidosis that underwent heart
transplantation during this period. RESULTS: 901 patients underwent heart
transplantation during the study period, of whom 4 patients had a pre-transplant
diagnosis of cardiac sarcoidosis and 8 patients had sarcoidosis identified in the
explanted heart. Patients with cardiac sarcoidosis had excellent post-transplant
outcomes with survival of 92% at one year and 83% at five years. Survival was
similar to patients that underwent heart transplantation for an alternate
diagnosis. We did not encounter recurrent cardiac sarcoidosis or progressive
extra-cardiac sarcoidosis during 1001 months of follow-up. CONCLUSIONS: Carefully
selected patients with advanced heart failure due to cardiac sarcoidosis have an
acceptable outcome after transplantation. Cardiologists should be aware that
reported experience of transplantation for cardiac sarcoidosis mostly represents
isolated cardiac sarcoidosis that was only diagnosed at pathological examination
of the explanted heart.
PMID- 26422566
TI - Efficacy and Safety of Rituximab in Connective Tissue Disease related
Interstitial Lung Disease.
AB - BACKGROUND: Pulmonary complications of connective tissue disease are being
identified more frequently with the advent of more sophisticated radiological
investigations. Limited previous studies have suggested Rituximab (RTX), a
chimeric monoclonal antibody with activity against CD-20, may benefit connective
tissue disease patients with pulmonary complications. We performed a
retrospective analysis of the efficacy and safety of RTX in patients attending a
tertiary referral centre. METHODS: Ten patients treated with RTX for pulmonary
complications of CTD in our institution were identified. Baseline demographics,
pre- and post-treatment investigations and adverse events were documented with an
average follow up time-frame of 12.3 months (range: 3 - 27). Statistical analysis
was performed using the Wilcoxan Signed-Rank test in SPSS. RESULTS: There was a
statistically significant improvement in pulmonary function, with a mean increase
of 19% in DLCO (median DLCO (ml/min/mmHg) pre-treatment vs. post-treatment: 13.94
vs. 19.34, p=0.028) and a mean increase of 13% in FVC (median FVC (L) pre
treatment vs. post-treatment: 3.47 vs.3.6, p=0.28). For patients with pulmonary
fibrosis (n=7), CT severity was improved on post-treatment scan, though this did
not reach statistical significance. There was a reduction in the number of
nodules seen on the follow-up scans of two patients without fibrosis. No patient
had a severe adverse reaction to RTX. CONCLUSIONS: Treatment with RTX resulted in
an objective, measurable improvement in pulmonary function and/or radiological
severity for the majority of patients included in the series. This was
statistically significant despite the small numbers included. These results
indicate a positive response to RTX with few complications of treatment.
PMID- 26422567
TI - Cathelicidin as a link between sarcoidosis and tuberculosis.
AB - SETTING: Sarcoidosis and tuberculosis share notable clinical, radiological,
histological, and immunological similarities. The importance of vitamin D has
long been investigated in these two granulomatous lung diseases. Cathelicidin is
an antimicrobial peptide of the innate immune system, directly induced by vitD3.
OBJECTIVE: To evaluate the role of cathelicidin in sarcoidosis and tuberculosis
development. DESIGN: The study included 30 consecutive patients with active lung
tuberculosis, 30 patients with sarcoidosis, and 20 healthy controls. 25
hydroxyvitamin D [25(OH)D] and cathelicidin levels were measured in blood
samples. RESULTS: Vitamin D levels were significantly higher (p<0.001) in
tuberculosis patients (22.5 +/- 9.96 ng/ml) than in sarcoidosis patients (11.75
+/- 8.92 ng/ml). Severe vitamin D deficiency was as frequent as 47% in
sarcoidosis patients compared to only 3% in tuberculosis patients. Cathelicidin
levels were significantly higher in the control group (120.37 +/- 41.03 pg/ml)
than in sarcoidosis (67.68 +/- 38.03 pg/ml) and tuberculosis (68.74 +/- 39.44
pg/ml) patients (p<0.001). However, no significant difference in cathelicidin
levels was observed between tuberculosis and sarcoidosis patients (p=0.966). The
optimum cathelicidin cut-off value to distinguish sarcoidosis patients from
healthy controls was 107.14 pg/ml (sensitivity 81.5%, specificity 71.2%).
CONCLUSION: Cathelicidin appears to play different roles in the development of
granulomatous lung disease.
PMID- 26422568
TI - Biomarkers to identify ILD and predict lung function decline in scleroderma lung
disease or idiopathic pulmonary fibrosis.
AB - BACKGROUND: SSc-ILD and IPF demonstrate significant morbidity and mortality.
Predicting disease progression is challenging in both diseases. OBJECTIVES: We
sought a serum biomarker that could identify patients with SSc-ILD or IPF and
prospectively predict short-term decline in lung function in these patients.
METHODS: 10 healthy controls, 5 SSc w/o ILD, 6 SSc-ILD and 13 IPF patients
underwent venesection. An array of cytokines including KL-6, SP-D and MMP7 were
measured. PFTs were obtained at baseline and six months. Cytokine measurements
were correlated with PFTs. RESULTS: KL-6 in IPF patients (633 ng/ml, IQR 492
1675) was significantly elevated compared to controls (198 ng/ml, IQR 52-360,
p<0.01) and SSc w/o ILD patients (192 ng/ml, IQR 0-524, p<0.05); KL-6 in SSc-ILD
patients (836 ng/ml, IQR 431-1303) was significantly higher than in controls
(p<0.05). SP-D was significantly higher in IPF patients (542 ng/ml, IQR 305-577)
compared to controls (137 ng/ml, IQR 97-284, p<0.01) or to SSc w/o ILD patients
(169 ng/ml, IQR 137-219, p<0.05). In comparison with controls (0.0 ng/ml, IQR 0.0
0.6), MMP7 was significantly higher in both IPF patients (2.85 ng/ml, IQR 1.5
3.6, p<0.05) and SSc-ILD patients (5.41 ng/ml, IQR 2.6-7.2, p<0.001). Using a cut
off level of 459ng/ml for KL-6 and of 1.28 ng/ml for MMP7, 18 out of 19 patients
with ILD had a serum value of either KL-6 or MMP7 above these thresholds. For all
ILD patients, baseline serum SP-D correlated with DeltaFVC %pred over six months
(r=-0.63, p=0.005, 95% CI -0.85 to -0.24). CONCLUSIONS: Combining KL-6 with MMP7
may be a useful screening tool for patients at risk of ILD. SP-D may predict
short-term decline in lung function.
PMID- 26422569
TI - Ocular and systemic features of sarcoidosis and correlation with the
International Workshop for Ocular Sarcoidosis diagnostic criteria.
AB - PURPOSE: To describe the ocular and systemic features in biopsy proven (definite)
and non-biopsy proven (clinical) ocular sarcoidosis and to compare the ocular
features with those proposed by the International Workshop for Ocular Sarcoidosis
(IWOS). METHODS: Retrospective chart review of 83 patients who attended a
tertiary referral uveitis clinic and were diagnosed with sarcoidosis. Patients
were divided into two groups based on the type of diagnosis: those who had tissue
biopsy confirmed diagnosis 'definite sarcoidosis' (n= 42; 50.60 %) and those who
had 'clinical sarcoidosis' (n= 41; 49.40%). Ocular and systemic manifestations,
including lung function tests and bronchoalveolar lavage findings were compared
in the two groups. The ocular features were also compared with the categories
laid down by the International Workshop on Ocular Sarcoidosis (IWOS). RESULTS:
The mean age at presentation was 38.75 years (SD=12.33), 55.42% patients were
female and mean follow-up was 24.35 months (SD=18.35). Trabecular meshwork
nodules and/or tent-shaped PAS (category II of IWOS) were observed more
frequently in patients with biopsy proven sarcoidosis (26.19 % v/s 9.76%;
p=0.08). After logistic regression analysis, the predictor coefficient curve
showed area under curve of 0.7262. Lymphocytosis (38.61% and 28.02%, p=0.93) and
monocytosis (55.11% and 53.83%, p=0.56) on bronchoalveolar lavage analysis was
present in both the groups, highlighting presence of granulomatous disease.
CONCLUSION: This study suggests high reliability for the clinical diagnosis of
ocular sarcoidosis in patients with signs recommended by IWOS and that our
diagnostic criteria are consistent with that of the IWOS.
PMID- 26422570
TI - Fibrosing interstitial lung diseases involve different pathogenic pathways with
similar outcomes.
AB - Fibrosing interstitial lung diseases (ILDs) are a large group of diseases
triggered by external or internal stimuli that can have similar outcomes, i.e.
lung fibrosis. Some ILDs are primarily fibro-proliferative disorders in which
alveolar loss and epithelial/fibroblastic proliferation and dysplasia lead to
lung fibrosis and architectural derangement, while other ILDs are considered
inflammatory disorders in which specific underlying conditions (with either an
external or an internal origin) can shift the pathogenic process to the fibro
proliferative pathway. The treatment of primarily inflammatory ILDs, regardless
of their tendency to switch to lung fibrosis usually consists of anti
inflammatory drugs (e.g. corticosteroids, cytostatic + immunosuppressive agents),
targeted 'biologic treatment' (e.g. anti TNF-alpha, anti CD20) and combinations
thereof. However, we have entered an era in which new drugs that specifically
target fibrosing ILDs, namely IPF, have emerged. Continuing laboratory research
and clinical studies will hopefully provide us with a more complete understanding
of the pathogenesis of fibrosing ILDs. Additionally, we are optimistic about the
discovery of new pharmacological targets for the treatment of these serious
diseases.The complex issues concerning fibrosing ILDs were addressed and
passionately discussed during the Prague postgraduate course and conference
devoted to these diseases (June 19th - 21th, 2014).
PMID- 26422571
TI - Efficacy and safety of surgical lung biopsy for interstitial disease. Experience
of 161 consecutive patients from a single institution in Italy.
AB - BACKGROUND: The role of surgical biopsy for interstitial lung disease (ILD) is
controversial, because of possible postoperative morbidity and mortality. We
aimed to assess the efficacy and safety of surgical biopsy for ILD. METHODS: We
retrospectively analysed the diagnostic performance and the postoperative
complications of 161 consecutive surgical lung biopsy procedures carried out in
suspected ILD cases that were undefined after multidisciplinary clinico
radiological evaluation. In 151 cases (93.8%) the biopsy was performed by video
assisted thoracoscopic surgery (VATS), in 6.2% by limited thoracotomy. RESULTS: A
specific histological diagnosis was obtained in 154 (95.7%) of the surgically
biopsied patients, while 4.3% remained histologically unclassified. The
predominant histological patterns were sarcoidosis (29.8 %), usual interstitial
pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) (24.2%), cryptogenic organizing
pneumonia (18.6%) and nonspecific interstitial pneumonia (8.1%). The
postoperative course was uneventful in 142 cases. In 19 patients (11.8%) we
observed postoperative complications, predominantly prolonged air leakage (5.0%
of all cases). Thirty-day postoperative mortality was 3.1%, mostly due to acute
exacerbation of respiratory insufficiency. Postoperative mortality independently
correlated with preoperative need of oxygen therapy (OR, 5.21; 95% CI, 1.19
22.95) and with UIP/IPF histology (OR, 5.67; 95% CI, 1.27-25.25). CONCLUSIONS:
Lung biopsy was performed mostly by VATS, with limited morbidity, and was
effective in yielding a specific histologic diagnosis in the vast majority of
undefined ILD cases. To optimize the outcome of surgical biopsy for specific
diagnosis of ILD, this procedure should be performed only exceptionally in
patients with critical respiratory illness as postoperative mortality risk in
these subjects is exceedingly high.
PMID- 26422572
TI - Long-term stable lung function and second uncomplicated pregnancy on sirolimus in
lymphangioleiomyomatosis (LAM).
AB - We present a patient with lymphangioleiomyomatosis (LAM) on long-term sirolimus
(now 79 months) who has had a second successful pregnancy. The second pregnancy
on uninterrupted low-dose sirolimus (plasma levels 3-5 mg/L) was uncomplicated
both with respect to mother and child suggesting that low-dose sirolimus might be
safe in selected pregnant patients with stable LAM. The long-term time course in
this patient is in agreement with recent reports of a long-term beneficial effect
of sirolimus in LAM. In this patient, the pregnancies did not seem to impair the
long-term improvement of lung-function on sirolimus.
PMID- 26422573
TI - Early detection of colon cancer by increased serum level of Krebs von den Lungen
6 in a patient with dermatomyositis-associated interstitial pneumonia.
AB - Krebs von den Lungen-6 (KL-6) is a high-molecular-weight glycoprotein which is
elevated in serum of patients with interstitial pneumonia (IP). Serum KL-6 level
is clinically used for the diagnosis of IP as well as the evaluation of its
disease activity. KL-6 is originally identified when exploring novel soluble
antigens in patients with lung cancer, and is known to be elevated in patients
with several malignant tumors. The risk of malignant tumors is high in IP
patients with polymyositis and dermatomyositis (PM/DM), and follow-up of KL-6
levels may allow earlier detection of such tumors. However, to date, there are
only a few reports showing the usefulness of following-up serum KL-6 levels for
finding malignant tumors in IP patients with PM/DM. Here, we described the first
patient in whom increased serum KL-6 led to the diagnosis of colon cancer during
follow-up of DM-associated IP.
PMID- 26422574
TI - Propionibacterium acnes isolated from lymph nodes of patients with sarcoidosis.
AB - Propionibacterium acnes has been repeatedly suggested as a candidate causative
agent of sarcoidosis. It is the only microorganism that has been isolated from
sarcoid lesions by bacterial culture so far and this has been described in
Japanese patients only. We report two non-Japanese patients in whom
mediastinoscopy was performed in order to obtain lymph node tissue for
histopathology, which was suggestive for sarcoidosis. Bacterial culture of these
uncontaminated mediastinal lymph nodes revealed P. acnes in both patients. As
shown in these two cases, P. acnes can be isolated from sterile biopsied sarcoid
lymph nodes of non-Japanese patients and supports the belief that there is an
etiologic link between P. acnes sarcoidosis. Further elucidation could provide an
opening to novel strategies using antibiotics for treating sarcoidosis.
PMID- 26422575
TI - Pulmonary manifestations revealing Rosai-Dorfman disease.
AB - Rosai-Dorfman disease is a rare non-Langerhans cell histiocytosis, mainly
involving cervical nodes. We present the case of a patient with a pulmonary form
of Rosai-Dorfman disease without peripheral or intra-thoracic lymph nodes,
characterized by the presence of pulmonary nodules and cysts associated with
bilateral pleural effusions.
PMID- 26422576
TI - Improved dose calculation accuracy for low energy brachytherapy by optimizing
dual energy CT imaging protocols for noise reduction using sinogram affirmed
iterative reconstruction.
AB - The goal of this study was to evaluate the noise reduction achievable from dual
energy computed tomography (CT) imaging (DECT) using filtered backprojection
(FBP) and iterative image reconstruction algorithms combined with increased
imaging exposure. We evaluated the data in the context of imaging for
brachytherapy dose calculation, where accurate quantification of electron density
rhoe and effective atomic number Zeff is beneficial. A dual source CT scanner was
used to scan a phantom containing tissue mimicking inserts. DECT scans were
acquired at 80 kVp/140Sn kVp (where Sn stands for tin filtration) and 100
kVp/140Sn kVp, using the same values of the CT dose index CTDIvol for both
settings as a measure for the radiation imaging exposure. Four CTDIvol levels
were investigated. Images were reconstructed using FBP and sinogram affirmed
iterative reconstruction (SAFIRE) with strength 1,3 and 5. From DECT scans two
material quantities were derived, Zeff and rhoe. DECT images were used to assign
material types and the amount of improperly assigned voxels was quantified for
each protocol. The dosimetric impact of improperly assigned voxels was evaluated
with Geant4 Monte Carlo (MC) dose calculations for an (125)I source in numerical
phantoms. Standard deviations for Zeff and rhoe were reduced up to a factor ~2
when using SAFIRE with strength 5 compared to FBP. Standard deviations on Zeff
and rhoe as low as 0.15 and 0.006 were achieved for the muscle insert
representing typical soft tissue using a CTDIvol of 40 mGy and 3mm slice
thickness. Dose calculation accuracy was generally improved when using SAFIRE.
Mean (maximum absolute) dose errors of up to 1.3% (21%) with FBP were reduced to
less than 1% (6%) with SAFIRE at a CTDIvol of 10 mGy. Using a CTDIvol of 40mGy
and SAFIRE yielded mean dose calculation errors of the order of 0.6% which was
the MC dose calculation precision in this study and no error was larger than +/
2.5% as opposed to errors of up to -4% with FPB. This phantom study showed that
the SAFIRE image reconstruction algorithm provided reduced standard deviations of
Zeff and rhoe in uniform regions of interest while preserving mean Zeff and rhoe
values. This resulted in improved material type assignment. The use of SAFIRE
improved brachytherapy dose calculations for the materials from the phantom
investigated in this study using (125)I.
PMID- 26422577
TI - [Benchmark experiment to verify radiation transport calculations for dosimetry in
radiation therapy].
AB - Monte Carlo simulations are regarded as the most accurate method of solving
complex problems in the field of dosimetry and radiation transport. In (external)
radiation therapy they are increasingly used for the calculation of dose
distributions during treatment planning. In comparison to other algorithms for
the calculation of dose distributions, Monte Carlo methods have the capability of
improving the accuracy of dose calculations - especially under complex
circumstances (e.g. consideration of inhomogeneities). However, there is a lack
of knowledge of how accurate the results of Monte Carlo calculations are on an
absolute basis. A practical verification of the calculations can be performed by
direct comparison with the results of a benchmark experiment. This work presents
such a benchmark experiment and compares its results (with detailed consideration
of measurement uncertainty) with the results of Monte Carlo calculations using
the well-established Monte Carlo code EGSnrc. The experiment was designed to have
parallels to external beam radiation therapy with respect to the type and energy
of the radiation, the materials used and the kind of dose measurement. Because
the properties of the beam have to be well known in order to compare the results
of the experiment and the simulation on an absolute basis, the benchmark
experiment was performed using the research electron accelerator of the
Physikalisch-Technische Bundesanstalt (PTB), whose beam was accurately
characterized in advance. The benchmark experiment and the corresponding Monte
Carlo simulations were carried out for two different types of ionization chambers
and the results were compared. Considering the uncertainty, which is about 0.7 %
for the experimental values and about 1.0 % for the Monte Carlo simulation, the
results of the simulation and the experiment coincide.
PMID- 26422578
TI - Incorporation of local dependent reliability information into the Prior Image
Constrained Compressed Sensing (PICCS) reconstruction algorithm.
AB - PURPOSE: The reduction of dose in cone beam computer tomography (CBCT) arises
from the decrease of the tube current for each projection as well as from the
reduction of the number of projections. In order to maintain good image quality,
sophisticated image reconstruction techniques are required. The Prior Image
Constrained Compressed Sensing (PICCS) incorporates prior images into the
reconstruction algorithm and outperforms the widespread used Feldkamp-Davis-Kress
algorithm (FDK) when the number of projections is reduced. However, prior images
that contain major variations are not appropriately considered so far in PICCS.
We therefore propose the partial-PICCS (pPICCS) algorithm. This framework is a
problem-specific extension of PICCS and enables the incorporation of the
reliability of the prior images additionally. MATERIAL AND METHODS: We assumed
that the prior images are composed of areas with large and small deviations.
Accordingly, a weighting matrix considered the assigned areas in the objective
function. We applied our algorithm to the problem of image reconstruction from
few views by simulations with a computer phantom as well as on clinical CBCT
projections from a head-and-neck case. All prior images contained large local
variations. The reconstructed images were compared to the reconstruction results
by the FDK-algorithm, by Compressed Sensing (CS) and by PICCS. To show the gain
of image quality we compared image details with the reference image and used
quantitative metrics (root-mean-square error (RMSE), contrast-to-noise-ratio
(CNR)). RESULTS: The pPICCS reconstruction framework yield images with
substantially improved quality even when the number of projections was very
small. The images contained less streaking, blurring and inaccurately
reconstructed structures compared to the images reconstructed by FDK, CS and
conventional PICCS. The increased image quality is also reflected in large RMSE
differences. CONCLUSIONS: We proposed a modification of the original PICCS
algorithm. The pPICCS algorithm incorporates prior images as well as information
about location dependent uncertainties of the prior images into the algorithm.
The computer phantom and experimental data studies indicate the potential to
lowering the radiation dose to the patient due to imaging while maintaining good
image quality.
PMID- 26422579
TI - Effects of chemotherapy on gene expression of lingual taste receptors in patients
with head and neck cancer.
AB - OBJECTIVES/HYPOTHESIS: We aimed to test the hypothesis that chemotherapy changes
the gene expression of taste receptors in the tongue to induce dysgeusia in
patients with head and neck cancer. STUDY DESIGN: Prospective observation study.
METHODS: We enrolled 21 patients who received chemoradiotherapy and five patients
who underwent radiotherapy for head and neck cancer. The messenger RNA (mRNA)
levels of the taste receptor subunits T1R1, T1R2, T1R3, and T2R5 were measured in
lingual mucosa scrapings obtained with a small spatula. The perception thresholds
of umami, sweet, and bitter tastes were assessed by the whole mouth gustatory
test. RESULTS: In four patients with severe stomatitis induced by
chemoradiotherapy, the mRNA levels of T1R1, T1R2, T1R3, and T2R5 in the lingual
mucosa were significantly decreased. However, in 17 patients with mild/moderate
stomatitis, the mRNA levels of T1R3 were significantly and transiently decreased,
whereas those of T1R1 and T1R2 remained unchanged and those of T2R5 mRNA were
significantly and transiently increased after chemotherapy. There was a
significant negative correlation between the perception thresholds of umami or
sweet tastes and lingual mRNA levels of T1R3 in patients with mild/moderate
stomatitis after chemotherapy. Although the perception threshold of bitter taste
remained unchanged, lingual mRNA levels of T2R5 were significantly increased in
patients who complained of phantogeusia after chemotherapy. CONCLUSION:
Chemotherapy specifically changed the gene expression of T1R3 and T2R5 in head
and neck cancer patients with mild/moderate stomatitis, resulting in both
dysgeusia of umami and sweet tastes as well as phantogeusia. LEVEL OF EVIDENCE:
4. Laryngoscope, 126:E103-E109, 2016.
PMID- 26422580
TI - Remission of Type 2 Diabetes Mellitus in Patients After Different Types of
Bariatric Surgery: A Population-Based Cohort Study in the United Kingdom.
AB - IMPORTANCE: To our knowledge, an observational study on the remission of type 2
diabetes mellitus (T2DM) after different types of bariatric surgery based on data
from general practice has not been carried out. OBJECTIVE: To assess the effect
of different types of bariatric surgery in patients with T2DM on diabetes
remission compared with matched control patients, and the effect of the type of
bariatric surgery on improvement of glycemic control and related clinical
parameters. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study
conducted from May 2013 to May 2014 within the Clinical Practice Research
Datalink involving 2978 patients with a record of bariatric surgery (2005-2012)
and a body mass index (calculated as weight in kilograms divided by height in
meters squared) of 35 or greater. We identified 569 patients with T2DM and
matched them to 1881 patients with diabetes without bariatric surgery. Data on
the use of medication and laboratory results were evaluated. EXPOSURES: Bariatric
surgery, stratified by type of surgery (gastric banding, Roux-en-Y gastric
bypass, sleeve gastrectomy, or other/unknown). MAIN OUTCOMES AND MEASURES:
Remission of T2DM (complete discontinuation of glycemic therapy, accompanied with
a subsequently recorded hemoglobin A1c level<6.0%). RESULTS: Among patients
undergoing bariatric surgery, we found a prevalence of 19.1% for T2DM. Per 1000
person-years, 94.5 diabetes mellitus remissions were found in patients who
underwent bariatric surgery compared with 4.9 diabetes mellitus remissions in
matched control patients. Patients with diabetes who underwent bariatric surgery
had an 18-fold increased chance for T2DM remission (adjusted relative rate [RR],
17.8; 95% CI, 11.2-28.4) compared with matched control patients. The greatest
effect size was observed for gastric bypass (adjusted RR, 43.1; 95% CI, 19.7
94.5), followed by sleeve gastrectomy (adjusted RR, 16.6; 95% CI, 4.7-58.4) and
gastric banding (adjusted RR, 6.9; 95% CI, 3.1-15.2). Body mass index and
triglyceride, blood glucose, and hemoglobin A1c levels sharply decreased during
the first 2 years after bariatric surgery. CONCLUSIONS AND RELEVANCE: Population
based data show that bariatric surgery strongly increases the chance for
remission of T2DM. Gastric bypass and sleeve gastrectomy have a greater effect
than gastric banding. Although the risks and possible adverse effects of surgery
should be weighed against its benefits, bariatric surgery and, in particular,
gastric bypass or sleeve gastrectomy may be considered as new treatment options
for T2DM.
PMID- 26422581
TI - Variable asialoglycoprotein receptor 1 expression in liver disease: Implications
for therapeutic intervention.
AB - AIM: One of the most promising strategies for the treatment of liver diseases is
targeted drug delivery via the asialoglycoprotein receptor (ASGPR). The success
of this approach heavily depends on the ASGPR expression level on parenchymal
liver cells. In this study, we assessed the mRNA and protein expression levels of
the major receptor subunit, ASGR1, in hepatocytes both in vitro and in vivo.
METHODS: In vitro, various liver cancer-derived cell lines were evaluated. In
vivo, we screened the ASGR1 mRNA on 59 hepatocellular carcinoma and matched non
neoplastic tissue using RNA microarray. In addition, 350 human liver specimens of
patients with hepatocellular carcinoma or non-neoplastic liver diseases were
screened for ASGR1 protein level using tissue microarray analysis. RESULTS: Our
data reveal that the ASGR1 mRNA expression directly correlates with the protein
level. We demonstrate that the ASGR1 expression is upregulated in cirrhotic
specimens and is significantly decreased with increasing hepatocellular carcinoma
grade. CONCLUSION: Because the ASGR1 expression levels are variable between
patients, our findings suggest that ASGPR-based targeting strategies should be
combined with ASGPR-companion diagnostics to maximize clinical benefit.
PMID- 26422582
TI - Intracellular delivery of 10-hydroxycamptothecin with targeted nanostructured
lipid carriers against multidrug resistance.
AB - 10-Hydroxycamptothecin (HCPT) is a clinical therapy agent against hepatoma. The
chemotherapy of HCPT is strongly obstructed by the emergence of multidrug
resistance (MDR), serious systemic toxicity, malfunction of rapid phagocytic and
renal clearance disorder which are undesirable for its chemotherapy. In this
paper, a drug delivery system (DDS) for HCPT has been developed in order to
overcome MDR. Nanostructured lipid carriers (NLC) coated with xyloglucan (XG) was
prepared by soya oil and XG consisting of side chains with galactose residues, a
terminal moiety that can be used to target HCPT to hepatoma. The therapeutic
potential of XG-NLC/HCPT was investigated on HepG2/HCPT cells and on human tumor
xenograft nude mouse model (implanted with HepG2/HCPT cells). XG-NLC/HCPT not
only indicated superior cytotoxicity against the drug resistant HepG2 cells but
also in vivo, generated a higher therapeutic effect. Systemic toxicity study
demonstrated that the carrier reduced systemic toxicity. XG-NLC/HCPT proved a
great potential to serve as DDS to overcome MDR of HepG2/HCPT cells. These
results suggested that XG NLC/HCPT represent a promising carrier for drug
delivery to the hepatoma and reverse the drug resistant of HepG2 cells and XG
could be exploited as a potential targeting device for liver tissue.
PMID- 26422583
TI - Persuasive appeals in road safety communication campaigns: Theoretical frameworks
and practical implications from the analysis of a decade of road safety campaign
materials.
AB - Communication campaigns are employed as an important tool to promote road safety
practices. Researchers maintain road safety communication campaigns are more
effective when their persuasive appeals, which are central to their communicative
strategy, are based on explicit theoretical frameworks. This study's main
objectives were to develop a detailed categorization of persuasive appeals used
in road safety communication campaigns that differentiate between appeals that
appear to be similar but differ conceptually, and to indicate the advantages,
limitations and ethical issues associated with each type, drawing on behavior
change theories. Materials from over 300 campaigns were obtained from 41
countries, mainly using road safety organizations' websites. Drawing on the
literature, five types of main approaches were identified, and the analysis
yielded a more detailed categorizations of appeals within these general
categories. The analysis points to advantages, limitations, ethical issues and
challenges in using different types of appeals. The discussion summarizes
challenges in designing persuasive-appeals for road safety communication
campaigns.
PMID- 26422584
TI - Multidisciplinary care of children with repaired esophageal atresia and
tracheoesophageal fistula.
AB - OBJECTIVES: Children with congenital esophageal atresia with tracheoesophageal
fistula (TEF) require complex medical and surgical care, but few guidelines exist
to guide the long term care of this population. The purpose of this study is to
describe the findings and initial management of a comprehensive aerodigestive
team in order to understand the ongoing needs of children with repaired TEF.
METHODS: A retrospective chart review was performed on children with TEF who were
seen in the multidisciplinary Aerodigestive Clinic at Children's Hospital
Colorado. Diagnostic studies were ordered based on physician discretion. RESULTS:
Twenty-nine children with TEF were evaluated (mean age 3.8 years) between 2010
and 2014. All children had symptoms attributed to breathing, swallowing, and
digestive difficulties. Less than half of the children had seen a pulmonary or
gastrointestinal specialist in the past year. Tracheomalacia was diagnosed in all
children who had a bronchoscopy (23/23), and the presence of dysphagia was
correlated with severe tracheomalacia. 7/25 children who had a swallow study had
aspiration. 7/25 children had a diagnosis of active reflux despite current
management. Four patients were diagnosed with bronchiectasis as a result of the
multidisciplinary evaluation. CONCLUSION: Although all children had persistent
aerodigestive symptoms, over 50% had not been seen by an appropriate
subspecialist in the year prior to the clinic visit. The multidisciplinary
evaluation resulted in new diagnoses of bronchiectasis and active reflux, which
can both lead to long-term morbidity and mortality. Children with TEF require
evaluation by multiple subspecialists to manage not only current symptoms but
also long term risks. Ongoing care should be guided by protocols based on known
risks. Pediatr Pulmonol. 2016;51:576-581. (c) 2015 Wiley Periodicals, Inc.
PMID- 26422586
TI - Understanding the surgical pitfalls in total mesorectal excision: Investigating
the histology of the perirectal fascia and the pelvic autonomic nerves.
AB - AIM: Excellent understanding of fasciae and nerves surrounding the rectum is
necessary for total mesorectal excision (TME). However, fasciae anterolateral to
the rectum and surrounding the low rectum are still poorly understood. We studied
the perirectal fascia enfolding the extraperitoneally located part of the rectum
in en-bloc cadaveric specimens and the University Medical Center Utrecht (UMCU)
pelvic dataset, and describe implications for TME. METHODS: Four donated human
adult cadaveric specimens (two males, two females) were obtained through the
Leeds GIFT Research Tissue Programme. Paraffin-embedded blocks were produced and
serially sectioned at 50 and 250 MUm intervals. Whole mount sections were stained
with haematoxylin & eosin, Masson's trichrome and Millers' elastin. Additionally,
the UMCU pelvic dataset including digitalised cryosections of a female pelvis in
three axes was studied. RESULTS: The mid and lower rectum were surrounded by a
multi-layered perirectal fascia, of which the mesorectal fascia (MRF) and
parietal fascia bordered the 'holy plane'. There was no extra constant fascia
forming a potential surgical plane. Nerves ran laterally to the MRF. More
caudally, the mesorectal fat strongly reduced and the MRF approached the rectal
muscularis propria. The MRF had a variable appearance in terms of thickness and
completeness, most prominently at the anterolateral lower rectum. CONCLUSION:
Dissection onto the MRF allows nerve preservation in TME. Rectal surgeons are
challenged in doing so as the MRF varies in thickness and shows gaps, most
prominently at the anterolateral lower rectum. At this site, the risk of entering
the mesorectum is great and may result in an incomplete specimen.
PMID- 26422587
TI - HER2 expression in oesophageal carcinoma and Barrett's oesophagus associated
adenocarcinoma: An Australian study.
AB - BACKGROUND: Several studies have evaluated the prognostic value of HER2 in
oesophageal cancer, but the prognostic influence of HER2 overexpression in
oesophageal cancer remains uncertain. The aim of this study was to assess the
incidence of HER2 positivity and relationship with clinicopathological features
in patients with oesophageal cancer. DESIGN: The study cohort consisted of 269
patients diagnosed with oesophageal carcinoma in a single institution. HER2
expression was analysed by immunohistochemistry (IHC) and silver in situ
hybridization (SISH) in 152 archival oesophageal cancer specimens. Survival
analysis was assessed using Hazard models. RESULTS: HER2 expression was IHC3+ in
14 (9.2%), IHC2+ in 14 (9.2%), IHC1+ in 57 (37.5%), and IHC0 in 67 (44.1%) cases.
SISH results confirmed that 15 specimens (9.9%) were HER2 gene amplified. Among
27 squamous cell carcinomas (SCCs) only 3.7% were HER2 positive whereas 11.2% of
125 adenocarcinomas were HER2 positive. The HER2 positive tumours were more
likely to occur in men (OR: 5.00, 95% CI: 1.69-14.29), smokers (OR: 10.00, 95%
CI: 4.17-25) and in patients with Barrett's oesophagus (OR: 8.33, 95% CI: 3.71
20.00). There was no significant difference in survival between the (HER2 +ve,
14.3 months vs HER2 -ve, 24.6 months, p = 0.42) CONCLUSION: A HER2 prevalence
rate of 9.9% was found among patients with oesophageal cancer and no correlation
with survival was detected overall.
PMID- 26422589
TI - Asymptomatic gingival nodule in the anterior maxilla.
PMID- 26422588
TI - Injectable hydrogel provides growth-permissive environment for human nucleus
pulposus cells.
AB - Degeneration of intervertebral discs (IVDs) results in an overall alteration of
the biomechanics of the spinal column and becomes a major cause of low back pain.
In this study, an injectable hydrogel composite is fabricated and characterized
as a potential scaffold for the treatment of degenerated IVDs. Crosslinking of
type II collagen-hyaluronic acid (HA) hydrogel with 1-ethyl-3(3-dimethyl
aminopropyl) carbodiimide (EDC) increases the gel stability against collagenase
digestion and reduces water uptake in comparison with non-crosslinked gel. Cell
viability assay exhibits the proliferation of human nucleus pulposus (HNP) cells
in hydrogels. The cells in non-crosslinked gel and the gel crosslinked with a low
concentration of EDC (0.1 mM) show superior cell viability and morphology
compared with cells in gels crosslinked with higher concentration of EDC.
Quantitative PCR assay demonstrates the gene expression of extracellular matrix
(ECM) by cells cultured in the gels. The expression of ECM genes by HNP cells in
the gels demonstrated the phenotypic change of the cells. This study suggests
that the type II collagen-HA hydrogel and crosslinked hydrogel (0.1 mM EDC) are
permissive matrix for the growth of HNP cells and can be potentially applied in
NP repair.
PMID- 26422590
TI - Human SAS-6 C-Terminus Nucleates and Promotes Microtubule Assembly in Vitro by
Binding to Microtubules.
AB - Centrioles are essential components of the animal centrosome and play crucial
roles in the formation of cilia and flagella. They are cylindrical structures
composed of nine triplet microtubules organized around a central cartwheel.
Recent studies have identified spindle assembly abnormal protein SAS-6 as a
critical component necessary for formation of the cartwheel. However, the
molecular details of how the cartwheel participates in centriolar microtubule
assembly have not been clearly understood. In this report, we show that the C
terminal tail (residues 470-657) of human SAS-6, HsSAS-6 C, the region that has
been shown to extend toward the centriolar wall where the microtubule triplets
are organized, nucleated and induced microtubule polymerization in vitro. The N
terminus (residues 1-166) of HsSAS-6, the domain known to be involved in
formation of the central hub of the cartwheel, did not, however, exert any effect
on microtubule polymerization. HsSAS-6 C bound to the microtubules and localized
along the lengths of the microtubules in vitro. Microtubule pull-down and
coimmunoprecipitation (Co-IP) experiments with S-phase synchronized HeLa cell
lysates showed that the endogenous HsSAS-6 coprecipitated with the microtubules,
and it mediated interaction with tubulin. Isothermal calorimetry titration and
size exclusion chromatography showed that HsSAS-6 C bound to the alphabeta
tubulin dimer in vitro. The results demonstrate that HsSAS-6 possesses an
intrinsic microtubule assembly promoting activity and further implicate that its
outer exposed C-terminal tail may play critical roles in microtubule assembly and
stabilizing microtubule attachment with the centriolar cartwheel.
PMID- 26422591
TI - The Association Between Premedical Curricular and Admission Requirements and
Medical School Performance and Residency Placement: A Study of Two Admission
Routes.
AB - PURPOSE: The curricular elements of undergraduate premedical education are the
subject of an ongoing debate. The Warren Alpert Medical School of Brown
University (AMS) matriculates students via the traditional premedical route (TPM)
and an eight-year baccalaureate/MD program-the Program in Liberal Medical
Education (PLME)-which provides students with a broad and liberal education.
Using the juxtaposition of these two admission routes, the authors aimed to
determine whether there is an association between highly distinct premedical
curricular and admission requirements and medical school performance and
residency placement. METHOD: The cohorts studied included all of the PLME (n =
295) and TPM (n = 215) students who graduated from the AMS between 2010 and 2015.
Outcome variables consisted of multiple measures of medical school performance,
including standardized multiple-choice examination scores and honors grades, and
residency placement. The authors employed unadjusted tests of averages and
proportions (independent t tests and chi-square tests) to compare variables.
RESULTS: The TPM students attained marginally, but statistically significantly,
higher average scores on standardized multiple-choice examinations than their
PLME counterparts. The number of undergraduate premedical science courses
completed by PLME students accounted for less than 4% of the variance in key
metrics of medical school performance. The residency placement record of the PLME
and TPM cohorts proved comparable. CONCLUSIONS: These findings suggest that the
association between medical school performance and residency placement and
undergraduate premedical curricular and admission requirements is weak. Further
study is needed to determine the optimal premedical preparation of students.
PMID- 26422592
TI - Health Reform and Academic Health Centers: Commentary on an Evolving Paradigm.
AB - The Patient Protection and Affordable Care Act (ACA), both directly and
indirectly, has had a demonstrable impact on academic health centers. Given the
highly cross-subsidized nature of institutional funds flows, the impact of health
reform is not limited to the clinical care mission but also extends to the
research and education missions of these institutions. This Commentary discusses
how public policy and market-based health reforms have played out relative to
expectations. The authors identify six formidable challenges facing academic
health centers in the post-ACA environment: finding the best mission balance;
preparing for the era of no open-ended funding; developing an integrated,
interprofessional vision; broadening the institutional perspective; addressing
health beyond clinical care; and finding the right leadership for the times.
Academic health centers will be well positioned for success if they can focus on
21st-century realities, reengineer their business models, and find
transformational leaders to change institutional culture and behavior.
PMID- 26422593
TI - From Impairment to Empowerment: A Longitudinal Medical School Curriculum on
Disabilities.
AB - PROBLEM: All physicians will care for individuals with disabilities; however,
education about disabilities is lacking at most medical schools. Most of the
schools that do include such education exclusively teach the medical model, in
which disability is viewed as an impairment to be overcome. Disability advocates
contest this approach because it overlooks the social and societal contexts of
disability. A collaboration between individuals with disabilities, educators, and
physicians to design a medical school curriculum on disabilities could overcome
these differences. APPROACH: A curriculum on disabilities for first- and second
year medical students was developed during the 2013-2014 academic year and
involved a major collaboration between a medical student, medical educators,
disability advocates, and academic disability specialists. The guiding principle
of the project was the Disability Rights Movement motto, "Nothing about us
without us." Two small-group sessions were created, one for each medical school
class. They included discussions about different models of disability, video and
in-person narratives of individuals with disabilities, and explorations of
concepts central to social perceptions of disability, such as power
relationships, naming and stigmatization, and disability as identity. OUTCOMES:
According to evaluations conducted after each session, students reported positive
feedback about both sessions. NEXT STEPS: Through this curriculum, first- and
second-year medical students learned about the obstacles faced by individuals
with disabilities and became better equipped to understand and address the
concerns, hopes, and societal challenges of their future patients. This inclusive
approach may be used to design additional curricula about disabilities for the
clinical and postgraduate years.
PMID- 26422594
TI - A Diversity 3.0 Update: Are We Moving the Needle Enough?
AB - Five years ago, in a previous Academic Medicine Commentary, the author asserted
that the move toward health reform and a more equitable health system required a
transformation of more than how we finance, deliver, and evaluate health care. It
also required a new role for diversity and inclusion as a solution to our
problems, rather than continuing to see it as just another problem to be fixed.
In this update, the author assesses the collective progress made by the nation's
medical schools and teaching hospitals in integrating diversity into their core
strategic activities, as well as highlighting areas for continued improvement.The
author identifies five new trends in diversity and inclusion within academic
medicine: broader definitions of diversity to include lesbian, gay, bisexual, and
transgender people and those who have disabilities; elevated roles for diversity
leaders in medical school administration; growing use of a holistic approach to
evaluating medical school applicants; recognition of diversity and inclusion as a
core marker of excellence; and appreciation of the significance of subpopulations
within minority and underrepresented groups.More work remains to be done, but
institutional initiatives to foster and prioritize diversity and inclusion
coupled with national efforts by organizations such as the Association of
American Medical Colleges are working to build the capacity of U.S. medical
schools and teaching hospitals to move diversity from a peripheral initiative to
a core strategy for improving the education of medical students and, ultimately,
the care delivered to all of our nation's people.
PMID- 26422595
TI - [Effects of a physical restraint removal program on older people with dementia in
residential care].
AB - OBJECTIVE: To analyse the results of removing physical restraints from elderly
patients with dementia living in nursing homes. This objective is part of a wider
process of change in residential care. METHODS: Quasi-experimental study
conducted in two residences from May 2010 to May 2012. Information was collected
at 7 time points and longitudinal analyses were performed. After training staff,
the physical restraints in El Puig centre were phased out, while in the Conarda
centre, restraints were still applied to elderly people. The main variables
studied were: falls, psychotropic medication prescriptions, different indicators
of mental impairment, and degree of dependence (Norton, NPI, Mini-mental,
Tinetti, Barthel). RESULTS: In the El Puig centre all the physical restraints
were removed. A slight improvement was seen in the number of falls, and their
consequences. The ANOVA showed significant improvements in the centre that
removed restraints in prescribing psychotropic medications, cognitive impairment,
and behavioural changes. DISCUSSION: It is shown that removing physical
restraints do not cause negative effects as regards the number of falls, and also
positively affects the welfare and independence of elderly people (through
changes in behaviour and mental impairment). Furthermore, it is demonstrated that
this program must be accompanied by the reduction and control of medicines
(withdrawal of the number of psychotropic prescriptions).
PMID- 26422597
TI - Conductive Inorganic-Organic Hybrid Distributed Bragg Reflectors.
AB - A conductive hybrid distributed Bragg reflector (DBR) is demonstrated, consisting
of inorganic and organic semiconductor films and assembled by a thermal
deposition technique. A maximum reflectance of 92.2% and a wide spectral width of
more than 70 nm are achieved. The hybrid DBR shows good electrical conductivity,
which provides the possibility of practical applications in novel optoelectronic
devices, such as electrically pumped organic vertical-cavity surface-emitting
lasers.
PMID- 26422596
TI - Nitroxide malonate methanofullerene as biomimetic model of interaction of
nitroxide species with antioxidants.
AB - Bis-nitroxide malonate methanofullerene (NO)2-MF was studied as a biomimetic
model of reduction-oxidation activity with natural compounds-cytochrome c (cyt
c), dihydroquercetin (DHQ), ascorbic acid (AA) and synthetic drug-1-(beta
oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine (xymedon((r))). (NO)2-MF may
be used as the component of Langmuir monolayers on an aqueous subphase and as the
adsorbate on silica gel. The activity of (NO)2-MF in the reaction with cyt c was
compared with the effect of nitroxide species such as gaseous nitric oxide,
2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) by using UV-vis and EPR
spectra. It has been shown, that iron(III) in cyt c(3+) under action (NO)2-MF was
reduced up to iron(II), similar effect was observed under the influence of
gaseous NO in aqueous solution, but reduction of iron(III) in heme cyt c was
reversible in the presence of TEMPO. Therefore, the state of Fe-heme in cyt c can
be used as the indicator of the interaction of cyt c with nitroxide species in
vitro. The interaction of cyt c, DHQ, xymedon((r)) with (NO)2-MF monolayers was
confirmed by the increasing of limiting area A0 from 0.88 nm(2) up to 1.70 nm(2)
of (NO)2-MF on the aqueous subphase, by the paramagnetism and UV-vis spectral
data changes. These results can be explained by appearance of oxoammonium ion
(NO(+))2-MF adlayers and monolayers. The antioxidant and regenerating effects
were shown when treating wounds by xymedon((r)) in the presence of additives
(0.001%) of (NO)2-MF in the experiments on the rats.
PMID- 26422598
TI - Sensory Processing and Its Relationship with Children's Daily Life Participation.
AB - AIMS: To investigate whether children with probable or definite differences in
sensory processing (SP) had participation restrictions, and the relationship
between Short Sensory Profile (SSP) scores and children's participation. METHODS:
The participants were parents of 64 children (mean age 8 years 1 month); 36 with
potential impairments in regulating sensory input and filtering out unnecessary
stimuli (29 boys, 7 girls) and 28 with typical SP abilities (25 boys, 3 girls).
Parents' completed the SSP and Participation in Childhood Occupations
Questionnaire (PICO-Q). The SSP score was used to categorize children as
potential SP impairment group and typical SP ability group. RESULTS: Children
categorized as having probable or definite differences in SP exhibited
significantly lower participation levels and enjoyment than children categorized
as having typical SP abilities. However, participation frequency between both
groups was similar. Six out of the seven SP impairment types had small to
moderate correlations with children's participation (r = 0.25-0.48, p < 0.05).
Multiple regression analyses indicated that only three impairment types
(Underresponsive/Seeks Sensation, Low Energy/Weak, and Visual/Auditory
Sensitivity) were significant predictors of PICO-Q participation domains.
CONCLUSIONS: The results suggest that children with potential SP impairments have
restrictions in the degree of participation and enjoyment. Three SP types were
related to specific participation domains, but they explained a small amount of
variance or none in some participation domains. Other variables should be
considered to identify determinants of children's participation.
PMID- 26422599
TI - Studies on the ultrastructure in Anacardium occidentale L. leaves from Amazon in
northern Brazil by scanning microscopy.
AB - Leaves surfaces have various structures with specific functions and contribute to
the relationship with the environment. On morphological studies are analyzed
various parameters, ranging from macro scale through the micro scale to the
nanometer scale, which contribute to the study of taxonomy, pharmacognosy, and
ecology, among others. Functional structures found in leaves are responsible for
the wide variety of surfaces and some behaviors are given in terms of cellular
adaptation and the presence or absence of wax. This study reports the
characterization of Anacardium occidentale L. leaf surface and the techniques
used therein. A set of scanning electron microscope (SEM) and atomic force
microscope (AFM) images performed on fresh leaf allowed observation of textured
and heterogeneous profiles on both sides. SCANNING 38:329-335, 2016. (c) 2015
Wiley Periodicals, Inc.
PMID- 26422600
TI - Outcomes of percutaneous pedicle screw fixation for spinal trauma and tumours.
AB - We investigated the clinical and radiological results of percutaneous pedicle
screw fixation in the management of spinal trauma and metastatic tumours. A
retrospective analysis was performed on a series of 14 patients who were operated
on from March 2009 to November 2011 by a single surgeon (RJM). Following a
radiological review (CT scan/MRI), six patients underwent short segment fixation,
while the remaining underwent long segment fixation. All patients had routine
follow-ups at 4, 6, 12months, and annually thereafter. Clinical examinations were
conducted preoperatively and postoperatively, and the length of operation, blood
loss, and postoperative pain relief were recorded. There was a single patient
with an incision site complication. The mean blood loss was 269mL. All of the
parameters demonstrated no significant differences between the trauma and the
tumour groups (p=0.10). The neurological power scores improved for all patients,
with the largest increase being from a score of 2 to 4. At follow-up, the
majority of patients had returned to their previous activities and had reduced
pain scores. One patient suffered high pain levels from other medical conditions
that were not related to the operation. Minimally invasive pedicle screw fixation
is a suitable option for patients with spinal tumours and fractures, with
acceptable safety and efficacy in this small retrospective patient series. We
have seen favourable results in our patients, who have experienced an increased
quality of life following their surgery.
PMID- 26422601
TI - Synthesis, Structural Characterization, and Chiroptical Studies of Bidentate
Salen-Type Lanthanide (III) Complexes.
AB - The salen-type ligand prepared with (R,R) diphenylethan-1,2-diamine and
salicylaldehyde provides stable and inert complexes KLnL2 upon simple reaction
with lanthanide halides or pseudohalides LnX3 (Ln = Tb(3+) -Lu(3+) ; X = Cl(-) or
TfO(-) ) of its potassium salt. All the complexes were completely characterized
through nuclear magnetic resonance (NMR), electronic circular dichroism (ECD) in
the UV and some (Er(3+) , Tm(3+) , Yb(3+) ) also with Near-IR ECD (NIR-ECD) and
luminescence (Tb(3+) , Tm(3+) ). Careful analysis of the NMR shifts demonstrated
that the complexes are isostructural in solution and afforded an accurate
geometry. This was further confirmed by means of Density Functional Theory (DFT)
optimization of the Lu(3+) complex, and by comparing the ligand-centered
experimental and time-dependent TD-DFT computed UV-ECD spectra. As final
validation, we used the NIR-ECD spectrum of the Yb(3+) derivative calculated by
means of Richardson's equations. The excellent match between calculated and
experimental ECD spectra confirm the quality of the NMR structure.
PMID- 26422602
TI - What do high school students say when they talk to their friends about substance
use? Exploring the content of substance-use-specific communication with friends.
AB - In this study, we examined the content of adolescents' conversations with their
friends about substance use, adolescents' reactions to such conversations, and
reasons why some adolescents did not engage in such conversations. Based on 25
semistructured interviews with high school students, we identified three themes:
informational, persuasive, and relational messages. Informational messages
included discussing how many peers use substances and clarifying rumors about a
friend's substance use. Persuasive messages involved direct anti-substance-use
messages (e.g., warning), direct pro-substance-use messages (e.g., legalizing
marijuana), indirect anti-substance-use messages (e.g., disliking their substance
use experience), and indirect pro-substance-use messages (e.g., intentions to use
substances). Relational messages included joking about substance use and
establishing code words for use. Adolescents reacted to their conversations in
several ways, such as shock and increased relational closeness. When adolescents
did not talk about substance use with their friend, they offered several reasons,
including low response efficacy and fear of ruining the friendship.
PMID- 26422603
TI - Bioinformatics Analyses of the Role of Vascular Endothelial Growth Factor in
Patients with Non-Small Cell Lung Cancer.
AB - PURPOSE: This study was aimed to identify the expression pattern of vascular
endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC) and to
explore its potential correlation with the progression of NSCLC. METHODS: Gene
expression profile GSE39345 was downloaded from the Gene Expression Omnibus
database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were
analyzed to identify the differentially expressed genes (DEGs). Then pathway
enrichment analysis of the DEGs was performed and protein-protein interaction
networks were constructed. Particularly, VEGF genes and the VEGF signaling
pathway were analyzed. The sub-network was constructed followed by functional
enrichment analysis. RESULTS: Total 1666 up-regulated and 1542 down-regulated
DEGs were identified. The down-regulated DEGs were mainly enriched in the
pathways associated with cancer. VEGFA and VEGFB were found to be the initiating
factor of VEGF signaling pathway. In addition, in the epidermal growth factor
receptor (EGFR), VEGFA and VEGFB associated sub-network, kinase insert domain
receptor (KDR), fibronectin 1 (FN1), transforming growth factor beta induced
(TGFBI) and proliferating cell nuclear antigen (PCNA) were found to interact with
at least two of the three hub genes. The DEGs in this sub-network were mainly
enriched in Gene Ontology terms related to cell proliferation. CONCLUSION: EGFR,
KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC
tumorigenesis. These genes and corresponding proteins may have the potential to
be used as the targets for either diagnosis or treatment of patients with NSCLC.
PMID- 26422604
TI - Does Publication Bias Inflate the Apparent Efficacy of Psychological Treatment
for Major Depressive Disorder? A Systematic Review and Meta-Analysis of US
National Institutes of Health-Funded Trials.
AB - BACKGROUND: The efficacy of antidepressant medication has been shown empirically
to be overestimated due to publication bias, but this has only been inferred
statistically with regard to psychological treatment for depression. We assessed
directly the extent of study publication bias in trials examining the efficacy of
psychological treatment for depression. METHODS AND FINDINGS: We identified US
National Institutes of Health grants awarded to fund randomized clinical trials
comparing psychological treatment to control conditions or other treatments in
patients diagnosed with major depressive disorder for the period 1972-2008, and
we determined whether those grants led to publications. For studies that were not
published, data were requested from investigators and included in the meta
analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not
result in publications, and two others never started. Among comparisons to
control conditions, adding unpublished studies (Hedges' g = 0.20; CI95%
0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the
psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover,
these findings may overestimate the "true" effect of psychological treatment for
depression as outcome reporting bias could not be examined quantitatively.
CONCLUSION: The efficacy of psychological interventions for depression has been
overestimated in the published literature, just as it has been for
pharmacotherapy. Both are efficacious but not to the extent that the published
literature would suggest. Funding agencies and journals should archive both
original protocols and raw data from treatment trials to allow the detection and
correction of outcome reporting bias. Clinicians, guidelines developers, and
decision makers should be aware that the published literature overestimates the
effects of the predominant treatments for depression.
PMID- 26422605
TI - Defining treatment response in trichotillomania: a signal detection analysis.
AB - The Massachusetts General Hospital Hairpulling Scale (MGH-HPS) and the NIMH
Trichotillomania Severity Scale (NIMH-TSS) are two widely used measures of
trichotillomania severity. Despite their popular use, currently no empirically
supported guidelines exist to determine the degrees of change on these scales
that best indicate treatment response. Determination of such criteria could aid
in clinical decision-making by defining clinically significant treatment
response/recovery and producing accurate power analyses for use in clinical
trials research. Adults with trichotillomania (N=69) participated in a randomized
controlled trial of psychotherapy and were assessed before and after treatment.
Response status was measured via the Clinical Global Impressions-Improvement
Scale, and remission status was measured via the Clinical Global Impressions
Severity Scale. For treatment response, a 45% reduction or 7-point raw score
change on the MGH-HPS was the best indicator of clinically significant treatment
response, and on the NIMH-TSS, a 30-40% reduction or 6-point raw score difference
was most effective cutoff. For disorder remission, a 55-60% reduction or 7-point
raw score change on the MGH-HPS was the best predictor, and on the NIMH-TSS, a
65% reduction or 6-point raw score change was the best indicator of disorder
remission. Implications of these findings are discussed.
PMID- 26422608
TI - Ordered FePdCu nanoisland arrays made by templated solid-state dewetting.
AB - Ordered FePdCu nanoisland arrays were formed by annealing at 600 degrees C,
which caused solid state dewetting of [Cu/Fe/Pd] multilayers deposited on self
assembled SiO2 nanospheres with a size of 100 nm. A single FePdCu island was
formed on the top of each SiO2 nanosphere. The structure of the obtained system
was studied by x-ray diffraction (XRD), while its magnetic properties were
studied by SQUID magnetometry. A partially ordered L10 alloy appeared in the
annealed films, leading to magnetic hardening of the material. The paper presents
the influence of the patterning on the system properties. It is shown that
templated dewetting is a method providing nanoislands with well-controlled sizes
and positions. The role of copper admixture in controlling the structural and
magnetic properties is also discussed.
PMID- 26422607
TI - Replication Inhibition of Hepatitis B Virus and Hepatitis C Virus in Co-Infected
Patients in Chinese Population.
AB - BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infections
contributes to a substantial proportion of liver disease worldwide. The aim of
this study was to assess the clinical and virological features of HBV-HCV co
infection. METHODS: Demographic data were collected for 3238 high-risk people
from an HCV-endemic region in China. Laboratory tests included HCV antibody and
HBV serological markers, liver function tests, and routine blood analysis. Anti
HCV positive samples were analyzed for HCV RNA levels and subgenotypes. HBsAg
positive samples were tested for HBV DNA. RESULTS: A total of 1468 patients had
chronic HCV and/or HBV infections. Among them, 1200 individuals were classified
as HCV mono-infected, 161 were classified as HBV mono-infected, and 107 were
classified as co-infected. The HBV-HCV co-infected patients not only had a lower
HBV DNA positive rate compared to HBV mono-infected patients (84.1% versus 94.4%,
respectively; P < 0.001). The median HCV RNA levels in HBV-HCV co-infected
patients were significantly lower than those in the HCV mono-infected patients
(1.18[Interquartile range (IQR) 0-5.57] versus 5.87[IQR, 3.54-6.71] Log10 IU/mL,
respectively; P < 0.001). Furthermore, co-infected patients were less likely to
have detectable HCV RNA levels than HCV mono-infected patients (23.4% versus
56.5%, respectively; P < 0.001). Those HBV-HCV co-infected patients had
significantly lower median HBV DNA levels than those mono-infected with HBV
(1.97[IQR, 1.3-3.43] versus 3.06[IQR, 2-4.28] Log10 IU/mL, respectively; P <
0.001). The HBV-HCV co-infection group had higher ALT, AST, ALP, GGT, APRI and
FIB-4 levels, but lower ALB and total platelet compared to the HBV mono-infection
group, and similar to that of the HCV mono-infected group. CONCLUSION: These
results suggest that co-infection with HCV and HBV inhibits the replication of
both viruses. The serologic results of HBV-HCV co-infection in patients suggests
more liver injury compared to HBV mono-infected patients, but is similar to HCV
mono-infection.
PMID- 26422606
TI - Analysis of Transmission of MRSA and ESBL-E among Pigs and Farm Personnel.
AB - Livestock-associated bacteria with resistance to two or more antibiotic drug
classes have heightened our awareness for the consequences of antibiotic
consumption and spread of resistant bacterial strains in the veterinary field. In
this study we assessed the prevalence of concomitant colonization with livestock
associated methicillin-resistant Staphylococcus aureus (LA-MRSA) and
enterobacteriaceae expressing extended-spectrum betalactamases (ESBL-E) in farms
at the German-Dutch border region. Nasal colonization of pigs with MRSA (113/547
(20.7%)) was less frequent than rectal colonization with ESBL-E (163/540
(30.2%)). On the individual farm level MRSA correlated with ESBL-E recovery. The
data further provide information on prevalence at different stages of pig
production, including abattoirs, as well as in air samples and humans living and
working on the farms. Notably, MRSA was detected in stable air samples of 34 out
of 35 pig farms, highlighting air as an important MRSA transmission reservoir.
The majority of MRSA isolates, including those from humans, displayed
tetracycline resistance and spa types t011 and t034 characteristic for LA-MRSA,
demonstrating transmission from pigs to humans. ESBL-E positive air samples were
detected on 6 out of 35 farms but no pig-to-human transmission was found.
Detection of ESBL-E, e.g. mostly Escherichia coli with CTX-M-type ESBL, was
limited to these six farms. Molecular typing revealed transmission of ESBL-E
within the pig compartments; however, related strains were also found on
unrelated farms. Although our data suggest that acquisition of MRSA and ESBL-E
might occur among pigs in the abattoirs, MRSA and ESBL-E were not detected on the
carcasses. Altogether, our data define stable air (MRSA), pig compartments (ESBL
E) and abattoir waiting areas (MRSA and ESBL-E) as major hot spots for
transmission of MRSA and/or ESBL-E along the pig production chain.
PMID- 26422609
TI - The Association of Maternal Lifestyle with Birth Defects in Shaanxi Province,
Northwest China.
AB - BACKGROUND: The main objective was to investigate the burden of birth defects
among alive infants and explore the impact of maternal lifestyle during pregnancy
on the burden of birth defects in Northwest China. METHODS: A stratified multi
stage sampling method was used to study infants born during 2010-2013 (and their
mothers) in Shaanxi province of Northwest China. Socio-demographic information
was collected using a structured questionnaire, and medical records from the
local hospitals were used to determine the final diagnosis of birth defects.
Poisson regression analysis was performed to assess the association between
maternal lifestyles during pregnancy and the burden of birth defects, while
adjusting for potential confounders. RESULTS: We sampled 29098 infants, of whom
629 (i.e. 216.17 per 10000) were observed to have congenital defects.
Cardiovascular system defects (77.32 per 10000) were found to be the most common.
Mothers who had ever consumed alcohol during pregnancy were found to have infants
with a higher prevalence of some categories of birth defects, including nervous
system (Prevalence Rate Ratio, PRR:14.67, 95% CI: 1.94, 110.92), cardiovascular
system (PRR:3.22, 95% CI: 1.02, 10.16) and oral clefts (PRR:9.02, 95% CI: 2.08,
39.10) in contrast to infants of mothers without any alcohol consumption.
Maternal passive smoking during pregnancy lead to the increased burden of
malformations of eye, ear, face and neck (PRR:1.95, 95% CI: 1.15, 3.33),
cardiovascular system (PRR:1.70, 95% CI: 1.25, 2.31) and respiratory system
(PRR:9.94, 95% CI: 2.37, 41.76) in their newborns. Further, tea or coffee
consumption during pregnancy was positively correlated with the burden of
specific birth defects, such as cardiovascular system (PRR: 2.44, 95% CI: 1.33,
4.46) and genital organs (PRR:14.72, 95% CI: 1.87, 116.11) among infants.
CONCLUSIONS: The prevalence of birth defects was high in Shaanxi province of
Northwest China. The unhealthy lifestyles of mothers during pregnancy may
increase the prevalence of congenital malformations. These findings in future may
have some important implications for prevention of birth defects in Northwest
China.
PMID- 26422610
TI - Activation of Spinal Stabilizers and Shoulder Complex Muscles During an Inverted
Row Using a Portable Pull-up Device and Body Weight Resistance.
AB - Youdas, JW, Keith, JM, Nonn, DE, Squires, AC, and Hollman, JH. Activation of
spinal stabilizers and shoulder complex muscles during an inverted row using a
portable pull-up device and body weight resistance. J Strength Cond Res 30(7):
1933-1941, 2016-We recorded muscle activation normalized to a maximum voluntary
isometric contraction (% MVIC) during an inverted body weight row using a
commercially available portable pull-up device. Surface electromyographic (EMG)
analysis was conducted on 13 male and 13 female subjects performing 4 inverted
row exercises: (a) pronated grip both feet weight-bearing (WB); (b) supinated
grip both feet WB; (c) pronated grip one leg WB; and (d) supinated grip single
leg WB. Nine muscles were analyzed: (a) posterior deltoid (PD), (b) latissimus
dorsi (LD), (c) biceps brachii (BB), (d) lower trapezius (LT), (e) upper
trapezius (UT), (f) lumbar multifidus (LM), (g) middle trapezius (MT), (h) lumbar
thoracis (LTh), and (i) rectus abdominis (RA). Normalized peak EMG activity was
examined separately for each muscle with 9 repeated measures analysis of variance
(ANOVA) at alpha = 0.05. Post hoc comparisons of EMG activation across exercises
for statistically significant ANOVAs were conducted with Bonferroni corrections
for multiple comparisons. We observed statistically significant differences in
EMG activation of the LD between supinated and pronated double-leg WB (p = 0.001)
condition. Additionally, we found statistical significance in the UT between
pronated and supinated single-leg WB (p = 0.007). No statistically significant
differences in muscle activation existed between single- and double-leg WB in any
muscles. Four muscles (BB, LD, LT, and PD) demonstrated very high (>61% MVIC) EMG
activation during all 4 exercise conditions. Three muscles (UT, MT, and LM)
demonstrated high (41-60% MVIC) activation, whereas 2 muscles (LTh and RA)
demonstrated moderate (21-40% MVIC) activation. Four inverted row exercises
activated the LD, UT, MT, LT, and BB at levels conducive to strengthening.
PMID- 26422611
TI - The 400- and 800-m Track Running Induces Inspiratory Muscle Fatigue in Trained
Female Middle-Distance Runners.
AB - Inspiratory muscle fatigue (IMF) may limit exercise performance. A few studies
have reported that IMF occurs after short-duration swimming exercise, but whether
short-duration running can induce IMF remains unclear. Intra-abdominal pressure
is increased during running through diaphragmatic activation to stabilize the
spine during movements of the upper limbs. This occurs along with the increased
inspiratory muscle effort associated with increased respirations during exercise;
thus, we hypothesized that short-duration running exercise would induce IMF. To
test this hypothesis, we measured maximal inspiratory pressure (MIP) before and
after 400- and 800-m track running sessions. Eight female middle-distance (400,
800 m) runners performed a 400- and 800-m running test. Maximal inspiratory
pressure was measured before and after each test using a portable autospirometer.
The mean MIPs were significantly lower after running than before running; values
obtained were 107 +/- 25 vs. 97 +/- 27 cmH2O (p = 0.01, effect size [ES] = 0.65)
and 108 +/- 26 vs. 92 +/- 27 cmH2O (p = 0.01, ES = 0.74) before vs. after the 400
and 800-m tests, respectively. The mean MIP after the 800-m test was
significantly lower than after the 400-m test (p = 0.04, ES = 0.48). There was no
correlation between IMF value and running time (r = 0.53 and r = -0.28 for either
the 400- and 800-m tests, respectively; p > 0.05). In conclusion, IMF occurs
after short-duration running exercise. Coaches could consider prescribing
inspiratory muscle training or warm-up in an effort to reduce the inevitable IMF
associated with maximal effort running.
PMID- 26422612
TI - Changes in Sprint and Jump Performances After Traditional, Plyometric, and
Combined Resistance Training in Male Youth Pre- and Post-Peak Height Velocity.
AB - The purpose of this study was to compare the effectiveness of 6-week training
interventions using different modes of resistance (traditional strength,
plyometric, and combined training) on sprinting and jumping performances in boys
before and after peak height velocity (PHV). Eighty school-aged boys were
categorized into 2 maturity groups (pre- or post-PHV) and then randomly assigned
to (a) plyometric training, (b) traditional strength training, (c) combined
training, or (d) a control group. Experimental groups participated in twice
weekly training programs for 6 weeks. Acceleration, maximal running velocity,
squat jump height, and reactive strength index data were collected pre- and
postintervention. All training groups made significant gains in measures of
sprinting and jumping irrespective of the mode of resistance training and
maturity. Plyometric training elicited the greatest gains across all performance
variables in pre-PHV children, whereas combined training was the most effective
in eliciting change in all performance variables for the post-PHV cohort.
Statistical analysis indicated that plyometric training produced greater changes
in squat jump and acceleration performances in the pre-PHV group compared with
the post-PHV cohort. All other training responses between pre- and post-PHV
cohorts were not significant and not clinically meaningful. The study indicates
that plyometric training might be more effective in eliciting short-term gains in
jumping and sprinting in boys who are pre-PHV, whereas those who are post-PHV may
benefit from the additive stimulus of combined training.
PMID- 26422613
TI - Influence of Load Carriage on High-Intensity Running Performance Estimation.
AB - Load carriage is a necessary burden for tactical athletes. A combination of
training modes, including aerobic conditioning and progressive load carriage, may
lead to improved performance. The critical speed (CS) concept enables the
practitioner to prescribe high-intensity interval training (HIIT) time limits
(TLIMs) from a single 3-minute all-out exercise test (3 MT). We sought to examine
the effect of a standard load carriage (18.86 kg) on CS and the finite running
capacity > CS (D'). A group of trained subjects (age: 26 +/- 5 years, height: 181
+/- 4 cm, body mass [BM]: 90 +/- 14 kg) completed a loaded and unloaded (UL) 3
MT. The CS was reduced by 0.66 +/- 0.24 m.s (p < 0.01) in the loaded condition.
There was a small nonsignificant increase in D' (21.25 +/- 39.53 m, p = 0.07).
The higher the % load carriage relative to BM is, the greater decline in CS (r =
0.83, p < 0.01). A revised CS with load carriage from the UL 3 MT may be
calculated using: adjusted CS = original CS + ([-0.0638 * %load]) + 0.6982. Our
results indicate that revised CS and TLIMs for fixed distance, fixed time, or
fixed speed HIIT prescriptions may be derived from a UL 3 MT. Such calculations
would enable more expeditious training for tactical athletes. We recommend
further research involving implementation of HIIT using this new method.
PMID- 26422614
TI - Modeling and Analyzing the Transmission Dynamics of HBV Epidemic in Xinjiang,
China.
AB - Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) which
affects livers. In this paper, we formulate a hepatitis B model to study the
transmission dynamics of hepatitis B in Xinjiang, China. The epidemic model
involves an exponential birth rate and vertical transmission. For a better
understanding of HBV transmission dynamics, we analyze the dynamic behavior of
the model. The modified reproductive number sigma is obtained. When sigma < 1,
the disease-free equilibrium is locally asymptotically stable, when sigma > 1,
the disease-free equilibrium is unstable and the disease is uniformly persistent.
In the simulation, parameters are chosen to fit public data in Xinjiang. The
simulation indicates that the cumulated HBV infection number in Xinjiang will
attain about 600,000 cases unless there are stronger or more effective control
measures by the end of 2017. Sensitive analysis results show that enhancing the
vaccination rate for newborns in Xinjiang is very effective to stop the
transmission of HBV. Hence, we recommend that all infants in Xinjiang receive the
hepatitis B vaccine as soon as possible after birth.
PMID- 26422616
TI - Clarification of the Identity of the Tea Green Leafhopper Based on Morphological
Comparison between Chinese and Japanese Specimens.
AB - Tea green leafhopper is one of the most dominant pests in major tea production
regions of East Asia. This species has been variously identified as Empoasca
vitis (Goethe), Jacobiasca formosana (Paoli) and Empoasca onukii Matsuda in
Mainland China, Taiwan and Japan, respectively. Recent study of DNA sequence data
suggested that treatment of this pest as different species in these three
adjacent regions is incorrect and that they were a single species; but the
correct scientific name for the species has remained unclear. Consistent with the
prior molecular evidence, morphological study shows that the male genital
characters of Chinese specimens are the same as those of specimens from Japan, so
the correct scientific name of tea green leafhopper in China is Empoasca
(Matsumurasca) onukii Matsuda.
PMID- 26422615
TI - The Influence of Second-Hand Cigarette Smoke Exposure during Childhood and Active
Cigarette Smoking on Crohn's Disease Phenotype Defined by the Montreal
Classification Scheme in a Western Cape Population, South Africa.
AB - BACKGROUND: Smoking may worsen the disease outcomes in patients with Crohn's
disease (CD), however the effect of exposure to second-hand cigarette smoke
during childhood is unclear. In South Africa, no such literature exists. The aim
of this study was to investigate whether disease phenotype, at time of diagnosis
of CD, was associated with exposure to second-hand cigarette during childhood and
active cigarette smoking habits. METHODS: A cross sectional examination of all
consecutive CD patients seen during the period September 2011-January 2013 at 2
large inflammatory bowel disease centers in the Western Cape, South Africa was
performed. Data were collected via review of patient case notes, interviewer
administered questionnaire and clinical examination by the attending
gastroenterologist. Disease phenotype (behavior and location) was evaluated at
time of diagnosis, according to the Montreal Classification scheme. In addition,
disease behavior was stratified as 'complicated' or 'uncomplicated', using
predefined definitions. Passive cigarette smoke exposure was evaluated during 3
age intervals: 0-5, 6-10, and 11-18 years. RESULTS: One hundred and ninety four
CD patients were identified. Cigarette smoking during the 6 months prior to, or
at time of diagnosis was significantly associated with ileo-colonic (L3) disease
(RRR = 3.63; 95% CI, 1.32-9.98, p = 0.012) and ileal (L1) disease (RRR = 3.54;
95% CI, 1.06-11.83, p = 0.040) compared with colonic disease. In smokers,
childhood passive cigarette smoke exposure during the 0-5 years age interval was
significantly associated with ileo-colonic CD location (RRR = 21.3; 95% CI, 1.16
391.55, p = 0.040). No significant association between smoking habits and disease
behavior at diagnosis, whether defined by the Montreal scheme, or stratified as
'complicated' vs 'uncomplicated', was observed. CONCLUSION: Smoking habits were
associated with ileo-colonic (L3) and ileal (L1) disease at time of diagnosis in
a South African cohort.
PMID- 26422618
TI - Reusing and recycling dialysis reverse osmosis system reject water.
PMID- 26422620
TI - Klotho upregulation by rapamycin protects against vascular disease in CKD.
AB - Medial arterial calcification involves chondrogenic/osteogenic
transdifferentiation of vascular smooth muscle cells (VSMCs). Zhao et al. report
that phosphate activates the mammalian target of rapamycin (mTOR) cascade in
VSMCs, leading to downregulation of Klotho. Furthermore, rapamycin was shown to
halt medial calcification. This effect was blunted in the absence of Klotho.
Given the concomitant anti-atherosclerotic effects of the mTOR inhibitor, this
agent has clinical potential as an inhibitor of intimal atherosclerosis and
medial calcification.
PMID- 26422621
TI - Relevance of TNF-alpha in the context of other inflammatory cytokines in the
progression of diabetic nephropathy.
AB - An ancillary paradigm that has evolved recently in the pathogenesis of diabetic
nephropathy includes subclinical microinflammation with influx of macrophages and
consequent generation of myriad proinflammatory cytokines and ensuing kidney
damage. Among various proinflammatory cytokines, tumor necrosis factor-alpha (TNF
alpha) has attracted the most attention, since it amplifies the inflammatory
network of cytokines, leading to worsening of the progression of diabetic
nephropathy. The article by Awad et al. examines the role of TNF-alpha in the
pathogenesis of experimental diabetic nephropathy.
PMID- 26422622
TI - Epigenetic regulation in acute kidney injury: new light in a dark area.
AB - Epigenetic mechanisms have been implicated in the pathogenesis of renal diseases,
including acute kidney injury (AKI). Mar et al. now unravel the acetylation and
methylation at histones that are associated with the transcription of key genes
in AKI. Notably, histone modifications display a remarkable heterogeneity in
ischemic and endotoxic AKI. Targeting epigenetic programs may offer novel
strategies to protect kidneys from AKI and enhance kidney repair and recovery.
PMID- 26422623
TI - Epigenetic control of podocyte differentiation: a new target of the renin
angiotensin system in kidney disease.
AB - Glomerular podocyte integrity is essential to limit protein filtration in the
urine. Hayashi et al. report that epigenetic mechanisms control podocyte
differentiation and that activation of the renin-angiotensin system in kidney
disease affects podocyte differentiation and proteinuria by resetting the
podocyte epigenome. These findings suggest that modulation of DNA methylation
could be a promising target for the control of proteinuric kidney disease.
PMID- 26422624
TI - Does early-start renal replacement therapy improve outcomes for patients with
acute kidney injury?
AB - There is a paucity of high-quality evidence to guide clinicians on thresholds for
commencement of renal replacement therapy (RRT) in critically ill patients with
acute kidney injury (AKI), and wide international practice variation. Wald et al.
report a pilot randomized trial examining accelerated use of RRT for moderate AKI
in the intensive care unit, providing a workable design for a definitive trial
examining the timing of RRT in critical illness.
PMID- 26422625
TI - Oral or intravenous iron for anemia correction in chronic kidney disease?
AB - Iron deficiency in patients with chronic kidney disease (CKD) can be corrected by
the oral or intravenous route. The natural intestinal barrier against iron
overload is circumvented by intravenous iron. The balance between benefit and
risk of high iron doses remains unclear. In a randomized controlled trial in CKD
patients, Agarwal et al. find similar effects of oral and intravenous iron on
hemoglobin levels and kidney function decline but more serious cardiovascular
events and infections with intravenous iron.
PMID- 26422626
TI - Re: Microparticles: markers and mediators of sepsis-induced microvascular
dysfunction, immunosuppression, and AKI.
PMID- 26422627
TI - The Authors Reply.
PMID- 26422628
TI - The bumpy lumpy kidney that dumped protein: granulomatous glomerular and
tubulointerstitial nephritis.
PMID- 26422629
TI - Pincer nails following arteriovenous fistula creation.
PMID- 26422630
TI - Oxalate nephropathy: a three-dimensional view.
PMID- 26422631
TI - Hyponatremia in a patient with obstructive jaundice.
PMID- 26422632
TI - Acute kidney injury after Chernobyl.
PMID- 26422633
TI - APACHE III Outcome Prediction in Patients Admitted to the Intensive Care Unit
with Sepsis Associated Acute Lung Injury.
AB - BACKGROUND AND OBJECTIVE: Acute Physiology and Chronic Health Evaluation (APACHE)
III score has been widely used for prediction of clinical outcomes in mixed
critically ill patients. However, it has not been validated in patients with
sepsis-associated acute lung injury (ALI). The aim of the study was to explore
the calibration and predictive value of APACHE III in patients with sepsis
associated ALI. METHOD: The study was a secondary analysis of a prospective
randomized controlled trial investigating the efficacy of rosuvastatin in sepsis
associated ALI (Statins for Acutely Injured Lungs from Sepsis, SAILS). The study
population was sepsis-related ALI patients. The primary outcome of the current
study was the same as in the original trial, 60-day in-hospital mortality,
defined as death before hospital discharge, censored 60 days after enrollment.
Discrimination of APACHE III was assessed by calculating the area under the
receiver operating characteristic (ROC) curve (AUC) with its 95% CI. Hosmer
Lemeshow goodness-of-fit statistic was used to assess the calibration of APACHE
III. The Brier score was reported to represent the overall performance of APACHE
III in predicting outcome. MAIN RESULTS: A total of 745 patients were included in
the study, including 540 survivors and 205 non-survivors. Non-survivors were
significantly older than survivors (59.71 +/- 16.17 vs 52.00 +/- 15.92 years, p <
0.001). The primary causes of ALI were also different between survivors and non
survivors (p = 0.017). Survivors were more likely to have the cause of sepsis
than non-survivors (21.2% vs. 15.1%). APACHE III score was higher in non
survivors than in survivors (106.72 +/- 27.30 vs. 88.42 +/- 26.86; p < 0.001).
Discrimination of APACHE III to predict mortality in ALI patients was moderate
with an AUC of 0.68 (95% confidence interval: 0.64-0.73). CONCLUSION: this study
for the first time validated the discrimination of APACHE III in sepsis
associated ALI patients. The result shows that APACHE III score has moderate
predictive value for in-hospital mortality among adults with sepsis-associated
acute lung injury.
PMID- 26422634
TI - Profile and Determinants of Neurocognitive Dysfunction in a Sample of Adult
Nigerians With Heart Failure.
AB - BACKGROUND: Heart failure (HF) in Africans is peculiar because subjects are
younger than whites and have lower socioeconomic and educational level in
addition to the high prevalence of hypertension-related etiology and increased
mortality. Whereas cognitive dysfunction have been demonstrated among whites with
HF, the prevalence and pattern of cognitive dysfunction among sub-Saharan African
patients with HF have not been evaluated against this background. OBJECTIVES: The
aim of this study is to determine the 1-year prevalence and the factors
contributing to cognitive dysfunction in a cohort of Nigerian patients with HF.
MATERIALS AND METHODS: In this cross-sectional case-control study, cognitive
performance was evaluated in 111 consecutive individuals (60 HF patients and 51
controls matched for age, gender, and level of education) using the Community
Screening Interview for Dementia, Word List Learning Delayed Recall, Boston
Naming Test, and Modified Token Test. Other clinical and disease-specific
variables were collated and correlated with cognitive performance. RESULTS: The
mean total Community Screening Interview for Dementia, Word List Learning Delayed
Recall, Boston Naming Test, and Modified Token Test scores were significantly
lower among HF patients (P = < .001). The prevalence of global cognitive
dysfunction was 90.0% in HF and 5.9% among controls (odds ratio, 15.3; 95%
confidence interval, 5.08-46.01). Elevated systolic blood pressure, increased
comorbidity index, and wide pulse pressure were significantly associated with
poorer performance on at least 1 neuropsychological test. Using a multivariate
linear regression analysis, pulse pressure retained its significance (P = .029;
95% confidence interval, -0.117 to -0.007) as the most important predictor of
cognitive dysfunction in the cohort of HF patients. CONCLUSION: Cognitive
dysfunction is prevalent among this sample of Nigerians with HF. Regular
cognitive screening is therefore advocated among this high-risk group.
Controlling comorbidities as well as blood pressure may improve cognitive
performance among patients with HF.
PMID- 26422635
TI - Is Knowledge Level of Coronary Heart Disease and Risk Factors Among Post
Percutaneous Coronary Intervention Patients Adequate?
AB - BACKGROUND: Percutaneous coronary intervention (PCI) is now commonly used in the
treatment of coronary heart disease. However, shorter hospital stays after
intervention may affect patients' knowledge and subsequent required lifestyle
changes. OBJECTIVE: The aim of this study is to investigate participants' risk
factor profile, knowledge of coronary heart disease, and the influence of
demographic and risk factors on this knowledge. METHODS: This prospective, cross
sectional 1-site study recruited both elective and emergency PCI patients
postdischarge. The questionnaire collected data on demographics, risk factor
profile, and coronary heart disease knowledge as measured on the Bergman Heart
Disease Knowledge Questionnaire. Bivariate and multivariate analyses were used to
analyze the influence of 11 risk and sociodemographic factors on knowledge.
RESULTS: The response rate was 67% (n = 84). The sample was mostly male and aged
65.79 +/- 9.9 years, and 59% had an elective PCI. Risk factor burden was high; 2
or more risk factors were seen in 66% of participants. Mean knowledge score
overall was 51%, with the highest score achieved in the risk factor domain (61%).
Lowest scores were in the medical and symptoms domains (both 46%). Neither the
bivariate nor the multivariate analyses were significant. A large proportion of
patients believed that coronary heart disease was no longer a concern for them
after PCI. CONCLUSIONS: As expected, the risk factor profile of post-PCI patients
was high. However, their knowledge levels and awareness were unrelated to risk
factor profile and poor in comparison with studies in other cardiac patients.
This, in addition to the short stay in hospital and the low attendance of this
cohort at cardiac rehabilitation, identifies this group of patients as a priority
for further targeted education. Innovations are needed to increase knowledge and
begin behavioral change predischarge after PCI. This should include target and
goal setting for lifestyle change to avail of this critical education
opportunity.
PMID- 26422636
TI - Falls in Patients With Heart Failure: A Systematic Review.
AB - BACKGROUND: Many heart failure patients show fall-related signs/symptoms
including postural hypotension, cerebellar injury, and cognitive impairments.
Falls contribute to injuries, increased healthcare use, and death, but falls have
been understudied in this population. OBJECTIVE: The purpose of this review is to
identify fall rates, fall injuries, and risk factors for falls in heart failure
patients. METHODS: A systematic literature review was conducted using MEDLINE,
CINAHL, PubMed, PsycINFO, and Cochrane Library to identify publications from
August 1973 to June 2013. Keywords were accidental falls, heart failure, fall
rates, fall injuries, and fall risk. Inclusion criteria were publications that
were primary data based, included heart failure sample, had falls/fall risk as
study variables, and were written in English language. Exclusion criteria were
quality improvement/evaluation, case reports/studies, news, opinions, narrative
reviews, meeting reports, reflections, and letters to editors. Data were
abstracted using a standardized data collection form. RESULTS: Four publications
met the inclusion criteria. In the first study, fall rate was 43%, which is
higher than the fall rates among community-dwelling older adults. Fall-related
injuries were not examined in any of studies. Benzodiazepines and digoxin were
identified as medications that increased risk of falls in 1 case-control study.
Loop diuretics were not significantly associated with falls in 1 cohort study. In
the fourth study, patients who had poor gait and balance were at greater risk of
falling. CONCLUSIONS: Future studies are needed to determine factors associated
with falls, characterize injuries resulting from falls, and most importantly
design testable interventions to prevent falls in heart failure patients.
PMID- 26422637
TI - A Ventricular Assist Device Recipient and Suicidality: Multidisciplinary
Collaboration With a Psychiatrically Distressed Patient.
AB - BACKGROUND: Ventricular assist device (VAD) recipients are at high risk of
depression and anxiety, and poor psychosocial functioning is associated with
worse medical outcomes. PURPOSE: We present a case of a 31-year-old depressed
patient who demonstrated passive suicidal behavior through multiple episodes of
noncompliance, including temporarily discontinuing warfarin (Coumadin) several
months after VAD implantation. The patient's psychosocial and medical histories
and outcomes are presented. CONCLUSIONS: This case underscores the importance of
pre-VAD as well and ongoing psychosocial evaluation and management for this
unique patient population. CLINICAL IMPLICATIONS: Medical teams who are treating
patients with cardiovascular disease who are under consideration for VAD or heart
transplantation need to be aware of the multitude of ways in which patients can
express depressed and suicidal mood and work with a multidisciplinary team to
treat such symptoms to optimize patients' success with VAD/heart transplantation.
PMID- 26422638
TI - Cardiac Rehabilitation Online Pilot: Extending Reach of Cardiac Rehabilitation.
AB - BACKGROUND: While cardiac rehabilitation (CR) is recommended for all patients
after an acute cardiac event, limitations exist in reach. OBJECTIVE: The purpose
of the current study was to develop and pilot a flexible online CR program based
on self-management principles "Help Yourself Online." METHODS: The program was
designed as an alternative to group-based CR as well as to complement traditional
CR. The program was based on existing self-management resources developed
previously by the Heart Research Centre. Twenty-one patients admitted to Cabrini
Health for an acute cardiac event were recruited to test the program. The program
was evaluated using qualitative and quantitative methods. RESULTS: Quantitative
results demonstrated that patients believed the program would assist them in
their self-management. Qualitative evaluation, using focus group and interview
methods with 15 patients, showed that patients perceived the online CR approach
to be a useful instrument for self-management. CONCLUSIONS: Broader implications
of the data include the acceptability of the intervention, timing of intervention
delivery, and patients' desire for additional online community support.
PMID- 26422639
TI - Comorbidities and Psychosocial Characteristics as Determinants of Dropout in
Outpatient Cardiac Rehabilitation.
AB - BACKGROUND: Despite the clear benefits of cardiac rehabilitation (CR), a
considerable number of patients drop out early. OBJECTIVE: Therefore, we wanted
to evaluate dropout in CR with a special focus on comorbidities and psychosocial
background. METHODS: Patients who attended CR after acute coronary syndrome,
cardiac surgery, or heart failure (N = 489) were prospectively included. Dropout
was defined as attending 50% of the training sessions or less (n = 96 [20%]).
Demographic and clinical characteristics, exercise parameters, and psychosocial
factors were analyzed according to dropout, and those with a trend toward a
significant difference (P < .10) were entered in a multivariate logistic model.
RESULTS: The presence of a cerebrovascular accident (4.18 [1.39-12.52]) involved
a higher risk of dropout, and a comparable trend was seen for the presence of
chronic obstructive pulmonary disease (2.55 [0.99-6.54]). Attending the training
program only twice per week also implicated a higher risk of an early withdrawal
(3.76 [2.23-6.35]). In contrast, patients on beta-blockers were less likely to
withdraw prematurely (0.47 [0.22-0.98]). Singles were more likely to drop out
(2.89 [1.56-5.35]), as well as those patients who were dependent on others to get
to CR (2.01 [1.16-3.47]). Finally, the reporting of severe problems on the
anxiety/depression subscale of the EuroQOL-5D questionnaire involved a higher
odds for dropout (7.17 [1.46-35.29]). CONCLUSIONS: Neither demographic
characteristics nor clinical status or exercise capacity could independently
identify patients who were at risk of dropout. The presence of comorbidities and
a vulnerable psychosocial background rather seem to play a key role in dropout.
PMID- 26422641
TI - Synthesis of alpha,beta-Unsaturated N-Sulfonyl Imides through Zinc-Catalyzed
Intermolecular Oxidation of N-Sulfonyl Ynamides.
AB - A novel zinc-catalyzed intermolecular oxidation of N-sulfonyl ynamides has been
developed. A variety of functionalized alpha,beta-unsaturated N-sulfonyl imides
are readily accessed by utilizing this approach, thus providing a viable
alternative to synthetically useful alpha,beta-unsaturated imides. Importantly,
the reaction is proposed to proceed by a vinyligous E2-type elimination pathway,
but not metal carbene pathway.
PMID- 26422640
TI - A Randomized Feasibility Trial of a New Lifestyle Referral Assessment Versus
Usual Assessment in an Acute Cardiology Setting.
AB - BACKGROUND: A healthy diet, taking exercise, and not smoking or consuming alcohol
in excess are important to reduce the risk of cardiovascular disease either alone
or in combination with statin medication. Health education, including providing
information to patients on healthy living and guidance on how to achieve it, is a
key nursing function. OBJECTIVES: This study aims first to assess the feasibility
of conducting a full-scale trial of lifestyle referral assessment as shown by
recruitment rate, data collection, and follow-up and second to assess proof of
concept and explore possible mechanisms of change. METHODS: This was a single
center, randomized, 2-arm, parallel-group, unblinded feasibility trial conducted
in an acute teaching hospital trust. Participants were followed up at 3 and 6
months after randomization. RESULTS: Eight hundred eighty-seven patients were
screened for eligibility, of whom 132 (15%) were randomized into the trial. Of
the patients allocated to the individualized assessment, 27% accepted referral or
self-referred by 3 months in comparison to 5% allocated to the usual assessment.
CONCLUSIONS: We demonstrated that a full-scale trial is feasible and that an
individualized approach increased the number of patients accepting referral to a
formal program and initiating lifestyle change. However, we should consider the
aim of the assessment and ways in which the process of change can be optimized in
order to produce long-term benefit for patients. TRIAL REGISTRATION: current
controlled trials ISRCTN41781196.
PMID- 26422642
TI - Dynamic Cross-Linking of Polymeric Binders Based on Host-Guest Interactions for
Silicon Anodes in Lithium Ion Batteries.
AB - We report supramolecular cross-linking of polymer binders via dynamic host-guest
interactions between hyperbranched beta-cyclodextrin polymer and a dendritic
gallic acid cross-linker incorporating six adamantane units for high-capacity
silicon anodes. Calorimetric analysis in the solution phase indicates that the
given host-guest complexation is a highly spontaneous and enthalpically driven
process. These findings are further verified by carrying out gelation experiments
in both aqueous and organic media. The dynamic cross-linking process enables
intimate silicon-binder interaction, structural stability of electrode film, and
controlled electrode-electrolyte interface, yielding enhanced cycling
performance. Control experiments using both alpha, gamma-CDp with different
cavity sizes and a guest molecule incorporating a single adamantane unit verified
that the enhanced cycle life originates from the host-guest interaction between
beta-cyclodextrin and adamantane. The impact of the dynamic cross-linking is
maximized at an optimal stoichiometry between the two components. Importantly,
the present investigation proves that the molecular-level tuning of the host
guest interactions can be translated directly to the cycling performance of
silicon anodes.
PMID- 26422643
TI - Interaction at the silicon/transition metal oxide heterojunction interface and
its effect on the photovoltaic performance.
AB - The interfacial reaction and energy level alignment at the Si/transition metal
oxide (TMO, including MoO3-x, V2O5-x, WO3-x) heterojunction are systematically
investigated. We confirm that the interfacial reaction appears during the thermal
deposition of TMO, with the reaction extent increasing from MoO3-x, to V2O5-x,
and to WO3-x. The reaction causes the surface oxidation of silicon for faster
electron/hole recombination, and the reduction of TMO for effective hole
collection. The photovoltaic performance of the Si/TMO heterojunction devices is
affected by the interface reaction. MoO3-x are the best hole selecting materials
that induce least surface oxidation but strongest reduction. Compared with H
passivation, methyl group passivation is an effective way to reduce the interface
reaction and improve the interfacial energy level alignment for better electron
and hole collection.
PMID- 26422644
TI - Reforming the Veterans Health Administration--Beyond Palliation of Symptoms.
PMID- 26422645
TI - Challenges for Medicare at 50.
PMID- 26422646
TI - Hypoxia Differentially Modulates the Genomic Stability of Clinical-Grade ADSCs
and BM-MSCs in Long-Term Culture.
AB - Long-term cultures under hypoxic conditions have been demonstrated to maintain
the phenotype of mesenchymal stromal/stem cells (MSCs) and to prevent the
emergence of senescence. According to several studies, hypoxia has frequently
been reported to drive genomic instability in cancer cells and in MSCs by
hindering the DNA damage response and DNA repair. Thus, we evaluated the
occurrence of DNA damage and repair events during the ex vivo expansion of
clinical-grade adipose-derived stromal cells (ADSCs) and bone marrow (BM)-derived
MSCs cultured with platelet lysate under 21% (normoxia) or 1% (hypoxia) O2
conditions. Hypoxia did not impair cell survival after DNA damage, regardless of
MSC origin. However, ADSCs, unlike BM-MSCs, displayed altered gammaH2AX signaling
and increased ubiquitylated gammaH2AX levels under hypoxic conditions, indicating
an impaired resolution of DNA damage-induced foci. Moreover, hypoxia specifically
promoted BM-MSC DNA integrity, with increased Ku80, TP53BP1, BRCA1, and RAD51
expression levels and more efficient nonhomologous end joining and homologous
recombination repair. We further observed that hypoxia favored mtDNA stability
and maintenance of differentiation potential after genotoxic stress. We conclude
that long-term cultures under 1% O2 were more suitable for BM-MSCs as suggested
by improved genomic stability compared with ADSCs.
PMID- 26422647
TI - Freeze-Drying of L-Arginine/Sucrose-Based Protein Formulations, Part 2:
Optimization of Formulation Design and Freeze-Drying Process Conditions for an L
Arginine Chloride-Based Protein Formulation System.
AB - We recently reported that the presence of chloride counter ions in freeze-dried l
arginine/sucrose formulations provided the greatest protein stability, but led to
low collapse temperatures and glass transition temperatures of the freeze
concentrates. The objectives of this study were to identify l-arginine chloride
based formulations and optimize freeze-drying process conditions to deliver a
freeze-dried product with good physical quality attributes (including cake
appearance, residual moisture, and reconstitution time). Additional properties
were tested such as thermal properties, cake microstructure, and protein physical
stability. Excipient concentrations were varied with and without a model protein
(bovine serum albumin, BSA). Formulations were frozen with and without annealing
or with and without controlled nucleation. Primary drying was conducted at high
and low shelf temperature. Cakes with least defects and optimum physical
attributes were achieved when protein to excipient ratios were high. Controlled
nucleation led to elegant cakes for most systems at a low shelf temperature.
Replacing BSA by a monoclonal antibody showed that protein (physical) stability
was slightly improved under stress storage temperature (i.e., 40 degrees C) in
the presence of a low concentration of l-arginine in a sucrose-based formulation.
At higher l-arginine concentrations, cake defects increased. Using optimized
formulation design, addition of l-arginine chloride to a sucrose-based
formulation provided elegant cakes and benefits for protein stability.
PMID- 26422648
TI - Clinic and Emergency Room Evaluation and Testing of Headache.
AB - BACKGROUND: Evaluation of the headache patient in the outpatient clinic and
emergency department (ED) has different focuses and goals. The focus of this
paper is to review the evaluation of patients in both settings with mention of
evaluation in the pediatric and pregnant patient population. The patient's
history should drive the practitioner's decision and evaluation choices. We
review recommendations made by the American Board of Internal Medicine and
American Headache Society through the Choosing Wisely Campaign, which has an
emphasis on choosing the right imaging modality for the clinical situation and
elimination/prevention of medication overuse headache, as well as the US Headache
Consortium guidelines for migraine headache. We will also review focusing on ED
evaluation of the pediatric patient and pregnant patient presenting with
headache. CONCLUSION: At the end of the review we hope to have provided you with
a framework to think about the headache patient and what is the appropriate test
in the given clinical setting in order to ensure that the patient gets the right
diagnosis and is set on a path to the appropriate management plan.
PMID- 26422649
TI - Fentanyl Patches to Supplement Ultrasound-Guided Nerve Blocks for Improving Pain
Control After Foot and Ankle Surgery: A Prospective Study.
AB - The analgesic effects of preoperative ultrasound-guided nerve blocks wear off
after about 12 hours, leaving some patients in substantial pain. Transdermal
fentanyl concentrations peak at 12 to 24 hours after application and maintain
this concentration for approximately 72 hours. We sought to determine whether
combining the use of a transdermal fentanyl patch with either a sciatic or
femoral-sciatic nerve block would improve pain control in patients undergoing
foot and/or ankle surgery. Consecutive patients in the no-patch control group (n
= 104) were enrolled from July 2011 to October 2011, and those in the treatment
group (n = 232) were enrolled from November 2011 to May 2012 and received a
transdermal patch (4.125 mg/7.5 cm(2) releasing 25 MUg of fentanyl per hour)
applied to their chest postoperatively. Pain was assessed using a visual analog
scale at 6, 12, 24, and 48 hours after surgery. The primary outcome measure was
the number of requests for additional postoperative pain medication. Additional
postoperative analgesia was requested by 49 of the 104 control patients (47.1%)
and 63 of the 232 treated patients (27.1%; p = .002). The mean pain scores were
also lower in the treatment group, with a statistically significant difference (p
< .05) at 12, 24, and 48 hours. Thus, patients receiving a fentanyl patch
combined with an ultrasound-guided nerve block required less supplemental
analgesia to maintain adequate pain control than did those receiving a nerve
block alone. In conclusion, a fentanyl patch is a useful adjunct to an ultrasound
guided nerve block in foot and ankle surgery.
PMID- 26422650
TI - The Gift Box Open Achilles Tendon Repair Method: A Retrospective Clinical Series.
AB - Previous biomechanical studies have shown that the gift box technique for open
Achilles tendon repair is twice as strong as a Krackow repair. The technique
incorporates a paramedian skin incision with a midline paratenon incision, and a
modification of the Krackow stitch is used to reinforce the repair. The wound is
closed in layers such that the paratenon repair is offset from paramedian skin
incision, further protecting the repair. The present study retrospectively
reviews the clinical results for a series of patients who underwent the gift box
technique for treatment of acute Achilles tendon ruptures from March 2002 to
April 2007. The patients completed the Foot Function Index and the American
Orthopaedic Foot and Ankle Society ankle-hindfoot scale. The tendon width and
calf circumference were measured bilaterally and compared using paired t tests
with a 5% alpha level. A total of 44 subjects, mean age 37.5 +/- 8.6 years,
underwent surgery approximately 10.8 +/- 6.5 days after injury. The response rate
was 35 (79.54%) patients for the questionnaire and 20 (45.45%) for the
examination. The mean follow-up period was 35.7 +/- 20.1 months. The
complications included one stitch abscess, persistent pain, and keloid formation.
One (2.86%) respondent reported significant weakness. Five (14.29%) respondents
indicated persistent peri-incisional numbness. The range of motion was full or
adequate. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot
scale score was 93.2 +/- 6.8) and the mean Foot Function Index score was 7.0 +/-
10.5. The calf girth and tendon width differences were statistically
significantly between the limbs. The patients reported no repeat ruptures, sural
nerve injuries, dehiscence, or infections. We present the outcomes data from
patients who had undergone this alternative technique for Achilles tendon repair.
The technique is reproducible, with good patient satisfaction and return to
activity. The results compared well with the historical repeat rupture rates and
incidence of nerve injury and dehiscence for open and percutaneous Achilles
tendon repairs.
PMID- 26422651
TI - MAP4K4 Is a Threonine Kinase That Phosphorylates FARP1.
AB - Mitogen-activated protein kinase 4 (MAP4K4) regulates the MEK kinase cascade and
is implicated in cytoskeletal rearrangement and migration; however, identifying
MAP4K4 substrates has remained a challenge. To ascertain MAP4K4-dependent
phosphorylation events, we combined phosphoproteomic studies of MAP4K4 inhibition
with in vitro assessment of its kinase specificity. We identified 235
phosphosites affected by MAP4K4 inhibition in cells and found that pTP and pSP
motifs were predominant among them. In contrast, in vitro assessment of kinase
specificity showed that MAP4K4 favors a pTL motif. We showed that MAP4K4 directly
phosphorylates and coimmunoprecipitates with FERM, RhoGEF, and pleckstrin domain
containing protein 1 (FARP1). MAP4K4 inhibition in SH-SY5Y cells increases
neurite outgrowth, a process known to involve FARP1. As FARP1 and MAP4K4 both
contribute to cytoskeletal rearrangement, the results suggest that MAP4K4 exerts
some of its effects on the cytoskeleton via phosphorylation of FARP1.
PMID- 26422653
TI - The effect of late infection and antibiotic treatment on capsular contracture in
silicone breast implants: A rat model.
AB - BACKGROUND: The effect of late infection on capsular contracture has yet to be
established, leaving a gap in clinical guidelines for the treatment patients with
breast implants. This trial is the first to assess if the treatment of these
infections can reverse this effect in an in vivo rat model and whether late
distant infections increase the incidence of capsular contracture. MATERIALS AND
METHODS: Three groups of female Wistar rats (n = 42) received two silicone
implants in separate dorsal, subcutaneous pockets. All groups except control
underwent injection of a human strain of methicillin-sensitive Staphylococcus
aureus (MSSA) at least 30 days after implantation, allowing for physiologic
capsule formation. The infection group received a peritoneal injection, inducing
a transient bacteremia, the treated group received a course of antibiotics
following bacterial inoculation, and a final group received no intervention and
served as control. RESULTS: Implants were removed 4 months after insertion, and
capsules measured for thickness and sent for bacterial quantification. Compared
to both the control and treated groups, capsule thickness in the infection group
was statistically greater (p < 0.05), a difference not observed between treated
and control groups. In addition, a statistically significant positive correlation
was found between capsule thickness and bacterial count (R = 0.614, p < 0.01).
CONCLUSIONS: The difference in thickness between the control capsules and those
from the infection group is an indication that bacterial contamination of a
capsule from a remote late infection may increase the incidence of capsular
contracture suggesting that treating late infections could in fact prevent
capsular contracture.
PMID- 26422652
TI - Nanotechnology and regenerative therapeutics in plastic surgery: The next
frontier.
AB - The rapid ascent of nanotechnology and regenerative therapeutics as applied to
medicine and surgery has seen an exponential rise in the scale of research
generated in this field. This is evidenced not only by the sheer volume of papers
dedicated to nanotechnology but also in a large number of new journals dedicated
to nanotechnology and regenerative therapeutics specifically to medicine and
surgery. Aspects of nanotechnology that have already brought benefits to these
areas include advanced drug delivery platforms, molecular imaging and materials
engineering for surgical implants. Particular areas of interest include nerve
regeneration, burns and wound care, artificial skin with nanoelectronic sensors
and head and neck surgery. This study presents a review of nanotechnology and
regenerative therapeutics, with focus on its applications and implications in
plastic surgery.
PMID- 26422654
TI - Analysis of the vertical mammaplasty design in skin-sparing mastectomy and
immediate autologous reconstruction.
AB - BACKGROUND: Skin-sparing mastectomy designs for immediate autologous breast
reconstruction include racquet, Wise, and vertical mammaplasty incisions. The
vertical design addresses ptosis while maintaining viable skin flaps. This study
compares the racquet to the vertical incision. METHODS: Immediate skin-sparing
autologous breast reconstructions by a single surgeon using either vertical or
racquet incisions from August 2006 to September 2011 were analyzed. Aesthetic
scoring was based on a Likert-scale assessment of scar appearance, shape,
preoperative versus postoperative aesthetic comparison, and overall aesthetic
outcome. Responses were analyzed using the Mann-Whitney test. RESULTS: Seventy
seven patients (48 racquets and 29 vertical) were included. Patient demographics
and complications did not differ. Vertical design reconstructions were used for
patients with higher-grade ptosis (p < 0.001). Significantly better-appearing
scars (3.8 vs. 3.5; p = 0.04) were observed in the vertical group. Vertical
reconstructions showed a trend toward significance in cosmetic improvement
compared with preoperative appearance (3.2 vs. 3.0; p = 0.06). There was no
difference in shape (vertical 3.6, racquet 3.6; p = 0.86) or in postoperative
aesthetic result (vertical 3.6, racquet 3.4; p = 0.41). CONCLUSIONS: Shape and
overall postoperative aesthetic appearance did not significantly differ despite
greater ptosis preoperatively in the vertical group, demonstrating the efficacy
of the vertical design in reconstruction. Vertical design reconstructions were
rated aesthetically superior to their pre-mastectomy appearance. Significantly
better scar scores in the vertical group reflect the camouflaged nature of
vertical incisions. These results demonstrate that the aesthetic outcome of the
vertical design reconstruction in ptotic breasts is as good as and potentially
superior to the racquet design reconstruction in non-ptotic breasts.
PMID- 26422655
TI - Sorafenib-Induced Eruption Mimicking Erythema Multiforme.
PMID- 26422656
TI - Protein profiles distinguish stable and progressive chronic lymphocytic leukemia.
AB - Patients with a stable chronic lymphocytic leukemia (CLL) double their blood
lymphocyte count in >5 years, but may develop progressive disease with
lymphocytes doubling in <12 months. To identify a protein signature for
progressive CLL, whole cell extracts of peripheral blood mononuclear cells from
patients with CLL (n=27) were screened using iTRAQ (isobaric tags for relative
and absolute quantification) analysis. A total of 84 differentially abundant
proteins were identified from patients with stable and progressive CLL.
Subsequently, 32 of these proteins were quantified by SRM (selected reaction
monitoring) using extracts of purified CD19+ CLL cells from patients (n=50).
Hierarchical clustering of these protein profiles showed two clusters of patients
that correlated with progressive and stable CLL, providing signatures that should
be useful for triaging patients. Some of the proteins in the progressive cluster
have not been linked with CLL, for example, glutamate dehydrogenase 1 and
transcription intermediary factor 1-beta.
PMID- 26422657
TI - Quantitative activation suppression assay to evaluate human bone marrow-derived
mesenchymal stromal cell potency.
AB - BACKGROUND AIMS: With the increasing use of cell therapies involving immune
modulatory cells, there is a need for a simple standardized method to evaluate
and compare the suppressive potency of different cell products. We used the
Karpas 299 (K299) cell line as the reference suppressor cell to develop a
standardized suppression assay to quantify the immune-modulatory capacity of bone
marrow-derived mesenchymal stromal cells (BM-MSCs). METHODS: Healthy donor CD4 T
cells were co-cultured with the K299 cell line or with third-party BM-MSCs. After
stimulation with anti-CD3/CD28 beads, CD154 activation and proliferation of CD4 T
cells were measured to calculate suppression. RESULTS: The K299 cell line
reproducibly suppressed both the activation and proliferation of healthy donor
CD4 T cells in a dose-dependent manner. A rapid (16-h) assay that was based on
activation-suppression was selected for development. In replicate testing, there
was an inherent variability of suppression of 11% coefficient of variation
between different responder T cells. Suppression by BM-MSCs on different
responders correlated with suppression by K299. We therefore used K299
suppression as the reference to define suppression potency of BM-MSCs in K299
Suppression Units. We found that inter-donor variability, passage number, method
of manufacture and exposure of BM-MSCs to steroids or interferon-gamma all
affected BM-MSC potency of suppression. CONCLUSIONS: This method provides a
platform for standardizing suppressor function to facilitate comparisons between
laboratories and for use as a cell product release assay.
PMID- 26422658
TI - Proteolytically active ADAM10 and ADAM17 carried on membrane microvesicles in
human abdominal aortic aneurysms.
AB - The intraluminal thrombus (ILT) of human abdominal aortic aneurysm (AAA) has been
suggested to damage the underlying aortic wall, but previous work found scant
activity of soluble proteases in the abluminal layer of the ILT, adjacent to the
aneurysm. We hypothesised that transmembrane proteases carried by membrane
microvesicles (MV) from dying cells remain active in the abluminal ILT. ILTs and
AAA segments collected from 21 patients during surgical repair were assayed for
two major transmembrane proteases, ADAM10 (a disintegrin and metalloprotease-10)
and ADAM17. We also exposed cultured cells to tobacco smoke and assessed ADAM10
and ADAM17 expression and release on MVs. Immunohistochemistry showed abundant
ADAM10 and ADAM17 protein in the ILT and underlying aneurysmal aorta. Domain
specific antibodies indicated both transmembrane and shed ADAM17. Importantly,
ADAM10 and ADAM 17 in the abluminal ILT were enzymatically active. Electron
microscopy of abluminal ILT and aortic wall showed MVs with ADAM10 and ADAM17. By
flow cytometry, ADAM-positive microvesicles from abluminal ILT carried the
neutrophil marker CD66, but not the platelet marker CD61. Cultured HL60
neutrophils exposed to tobacco smoke extract showed increased ADAM10 and ADAM17
content, cleavage of these molecules into active forms, and release of MVs
carrying mature ADAM10 and detectable ADAM17. In conclusion, our results
implicate persistent, enzymatically active ADAMs on MVs in the abluminal ILT,
adjacent to the aneurysmal wall. The production of ADAM10- and ADAM17-positive
MVs from smoke-exposed neutrophils provides a novel molecular mechanism for the
vastly accelerated risk of AAA in smokers.
PMID- 26422660
TI - Preparation, optical and electrical properties of PTCDA nanostructures.
AB - Film, nanorods (NRs), nanowires (NWs), and nanoparticles (NPs) of perylene
3,4,9,10-tetracarboxylic dianhydride (PTCDA) were prepared by organic molecular
beam deposition (OMBD) on porous anodic alumina oxide (AAO) at different
substrate temperatures (Ts). Scanning electron microscopy (SEM) study showed that
the morphologies of the nanostructures (NS) formed on AAO strongly depend on the
Ts. The absorption spectra of different PTCDA NS present strong absorbance in the
wavelength range of 400-600 nm, and the photoluminescence (PL) spectra show a
blue shift as Ts increases. The current versus voltage (I-V) characteristic
illustrates that the electrical conductivity of the single-crystal NW is about 3
+/- 0.1 S m(-1), which is much higher than the conductivity of PTCDA film
reported previously.
PMID- 26422659
TI - Mitochondrial Dysfunction Due to Lack of Manganese Superoxide Dismutase Promotes
Hepatocarcinogenesis.
AB - AIMS: One of the cancer hallmarks is mitochondrial dysfunction associated with
oxidative stress. Among the first line of defense against oxidative stress is the
dismutation of superoxide radicals, which in the mitochondria is carried out by
manganese superoxide dismutase (MnSOD). Accordingly, carcinogenesis would be
associated with a dysregulation in MnSOD expression. However, the association
studies available so far are conflicting, and no direct proof concerning the role
of MnSOD as a tumor promoter or suppressor has been provided. Therefore, we
investigated the role of MnSOD in carcinogenesis by studying the effect of MnSOD
deficiency in cells and in the livers of mice. RESULTS: We found that loss of
MnSOD in hepatoma cells contributed to their conversion toward a more malignant
phenotype, affecting all cellular properties generally associated with metabolic
transformation and tumorigenesis. In vivo, hepatocyte-specific MnSOD-deficient
mice showed changed organ architecture, increased expression of tumor markers,
and a faster response to carcinogenesis. Moreover, deficiency of MnSOD in both
the in vitro and in vivo model reduced beta-catenin and hypoxia-inducible factor
1alpha levels. INNOVATION: The present study shows for the first time the
important correlation between MnSOD presence and the regulation of two major
pathways involved in carcinogenesis, the Wnt/beta-catenin and hypoxia signaling
pathway. CONCLUSION: Our study points toward a tumor suppressive role of MnSOD in
liver, where the Wnt/beta-catenin and hypoxia pathway may be crucial elements.
PMID- 26422662
TI - Distinguishing shyness and sociability in children: An event-related potential
study.
AB - Shyness and sociability are independent personality dimensions, each with
distinct behavioral and psychophysiological correlates that are conserved across
development, culture, and phylogeny. However, relatively little is known
regarding how shyness and sociability are instantiated in the brain, particularly
during childhood and during the processing of nonsocial stimuli. Using a three
stimulus auditory oddball task, we examined whether variations in shyness and
sociability were related to the N200 and P300 event-related potential (ERP) brain
responses to processing task-relevant, novel, and standard auditory tones in 53
typically developing 10-year-old children. ERP amplitudes were measured at four
midline scalp sites: Fz, FCz, Cz, and Pz. We found that increases in shyness were
correlated with increases in target P300 amplitudes across all four head sites,
increases in standard P300 amplitudes, and decreases in target P300 latencies in
anterior sites. No relations were found for sociability and P300 responses. We
also found that P300 amplitude in the frontal region to standard tones mediated
the relation between conflicted shyness (i.e., high shyness and high sociability)
and emotional instability. These results suggest that shyness and sociability are
distinguishable on neurocognitive measures and that these neurocognitive measures
may be putative mechanisms in understanding risk for emotional instability and a
broad range of dysregulated behavioral problems observed in individuals
characterized by conflicted shyness.
PMID- 26422661
TI - Maternal negative affect during infancy is linked to disrupted patterns of
diurnal cortisol and alpha asymmetry across contexts during childhood.
AB - Maternal negative affect in the early environment is believed to sensitize long
term coping capacities in children. Yet, little work has identified physiological
systems associated with coping responses, which may serve as mechanisms for links
between early maternal negativity and child outcomes. Using a longitudinal twin
sample (N=89), we found that high levels of maternal negative affect during
infancy were associated with dysregulation of diurnal cortisol and
electroencephalograph (EEG) asymmetry, two physiological systems that may support
active approach-oriented coping when children are 7years old. Flattened slopes of
diurnal cortisol were also associated with greater numbers of concurrent
overanxious behaviors in children. A mediation analysis supported the role of
dysregulated diurnal cortisol as a mediator of the link between maternal negative
affect in the early environment and childhood risk for anxiety problems.
PMID- 26422663
TI - Understanding differences in alcohol consumption and depressed mood between U.S.-
and foreign-born Asian and Caucasian college students.
AB - The number and proportion of foreign-born individuals in the U.S. population has
increased in recent decades. From 1970 to 2007, the foreign-born population more
than tripled to approximately 37 million (U.S. Census Bureau, 1997 , 2008 ).
Foreign-born students are a key subpopulation of college students. About 23% of
U.S. undergraduate college students in 2007-2008 were either born outside of the
United States (10%) or were children of at least one first-generation immigrant
parent (13%; National Center for Education Statistics, U.S. Department of
Education [NCES], 2012 ). Asian students constitute the majority (30%) of foreign
born undergraduates. Although foreign-born Asian students compose nearly one
quarter of the college population, limited research has examined how rates of
alcohol use and depression differ between foreign-born and U.S.-born Asian
college students (Gonzalez, Reynolds, & Skewes, 2011 ; Ralston & Palfai, 2012 ).
The limited research is worrisome given their increasing rates of college
enrollment (U.S. Census Bureau, 2011 ), alcohol consumption (Aud, Fox, &
KewalRamani, 2010 ), alcohol abuse and dependence (Grant et al., 2004 ), and
underutilization of mental health services (U.S. Department of Health and Human
Services, 2001 ). Collectively, these factors point to the need for further
research tailored to Asian college drinkers.
PMID- 26422664
TI - Chemistry of Urban Grime: Inorganic Ion Composition of Grime vs Particles in
Leipzig, Germany.
AB - Deposition of atmospheric constituents--either gas phase or particulate--onto
urban impervious surfaces gives rise to a thin "urban grime" film. The area
exposed by these impervious surfaces in a typical urban environment is comparable
to, or greater than, that of particles present in the urban boundary layer;
however, it is largely overlooked as a site for heterogeneous reactions. Here we
present the results of a field campaign to determine and compare the chemical
composition of urban grime and of particles collected simultaneously during the
autumn of 2014 at an urban site in central Leipzig, Germany. We see dramatically
reduced ammonium and nitrate levels in the film as compared to particles,
suggesting a significant loss of ammonium nitrate, thus enhancing the mobility of
these species in the environment. Nitrate levels are 10% lower for films exposed
to sunlight compared to those that were shielded from direct sun, indicating a
possible mechanism for recycling nitrate anion to reactive nitrogen species.
Finally, chloride levels in the film suggest that urban grime could represent an
unrecognized source of continental chloride available for ClNO2 production even
in times of low particulate chloride. Such source and recycling processes could
prove to be important to local and regional air quality.
PMID- 26422666
TI - [Dissection of the wired endotracheal tube's lumen during general anesthesia: a
case report].
AB - OBJECTIVE: The aim of this study is to report a case of a clinically significant
obstruction during mechanical ventilation caused by the dissection of the wired
endotracheal tube's lumen during general anesthesia in a pediatric patient. CASE
REPORT: A12-years old patient undergoing general anesthesia for open appendectomy
was intubated with a wired endotracheal tube and difficult removal of the guide.
After starting the mechanical ventilation, there was increased expiratory
fraction of CO2 and need for increased inspiratory pressure. Chance of
complications with higher incidences were raised and treated unsuccessfully.
Finally, during patient reintubation, the dissection of the endotracheal tube
lumen was observed, and ventilation was restored to normal. CONCLUSION:
Anesthesia involves numerous possible complications. Suspicion and constant
vigilance are essential for early diagnosis and treatment of any threat to the
individual integrity. This case is relevant for emphasizing a possible very rare
complication related to airway, which can quickly cause hypoxia and irreversible
damage. Thus, this case contributes to the detection of this complication more
frequently.
PMID- 26422667
TI - The Effect of the Pressure Exerted on the Maternal Abdominal Wall by the US Probe
on Fetal MCA Peak Systolic Velocity.
AB - Purpose To quantify the pressure exerted on the maternal abdominal wall during
ultrasound examination and evaluate its effect on the fetal middle cerebral
artery (MCA) peak systolic velocity (PSV). Materials and Method Gravid women with
singleton pregnancies in their 2nd-3 rd trimester undergoing fetal sonographic
evaluation for various indications were recruited. Each subject underwent
transabdominal US measuring fetal distance from the probe, abdominal thickness,
amniotic fluid index and biophysical profile. The applied pressure was measured
simultaneously using an electronic pressure sensor attached directly to the US
probe. For each subject baseline values of the pressure required for proper
visualization were obtained. Fetal MCA was then demonstrated using color Doppler
US. The PSV was measured at different pressure ranges with each subject used as
her own control. Care was taken not to exceed the baseline pressure for each
subject. Results 29 women were recruited. 24 subjects (82.7 %) demonstrated a
statistically significant positive correlation between the pressure exerted and
MCA-PSV (R-0.37, p < 0.0001). Of these, 4 subjects (13.8 % of study population)
demonstrated elevation of PSV values above 1.29 MOM and 5 subjects (17.2 %)
demonstrated elevation of PSV values above 1.5 MOM for gestational age with
increasing pressure. In total, 9 subjects (31 %) demonstrated significant changes
in the MCA-PSV measurements (owing to increase in pressure applied) that could
potentially falsely influence clinical obstetric diagnosis and management.
Conclusion The pressure exerted on the maternal abdominal wall during US
examination is an important parameter, producing clinically significant
measurable changes in fetal MCA hemodynamics. Further study is needed in order to
demonstrate the potential effect of pressure as a parameter influencing the
diagnostic accuracy of the MCA-PSV in the setting of fetal anemia.
PMID- 26422668
TI - Optimized Sonographic Weight Estimation of Fetuses over 3500 g Using Biometry
Guided Formula Selection.
AB - Purpose The Hadlock et al. formula tends to underestimate fetal weight, in
particular > 3500 g. At the high end of the range, the Merz et al. formula is
more accurate, but becomes less so in smaller fetuses. This study was designed to
improve fetal weight estimation in fetuses > 3500 g by identifying the fetal
biometric parameter providing the most reliable guidance to optimal formula
selection. Materials and Methods Regression analysis of 12 032 pregnancies showed
that multiplication of abdominal circumference by femur length (AC * FL) gave the
best choice of appropriate formula: Hadlock for AC * FL < 24 600, Merz for those
>= 24 600. We then tested this rule, ('Zurich method'), prospectively in 4073
pregnancies, comparing it with the Hadlock, Merz and the Kehl formulas. Birth
weights were merged into 7 categories (< 1500 to >= 4000 g, interval of 500 g).
The percentage error (PE) and absolute percentage error (APE) were calculated.
Results The PE using the Zurich method was lower in both > 3500 g groups than
with the Hadlock formula alone (3500 - 3999 g: 0.9 % vs. - 5.3 %, > 4000 g: - 3.2
% vs. - 8.6 %), similar to that with the Merz formula alone, and lower than with
the Kehl formulas (3500 - 3999 g: - 9.0 % vs. - 3.2 %, > 4000g: - 5.1 % vs. 0.9
%). The Zurich method and Hadlock formula also shared the lowest PE in the < 1500
g group: 0.2 % vs. 6.8 % (Kehl) vs. 9.6 % (Merz). In terms of APE the Zurich
method performed almost as well as the Merz formula in the > 4000 g group, while
sharing the lowest value with the Hadlock formula in the < 1500 g group (8.2 %
vs. 10.5 % [Kehl], 23.6 % [Merz]). Conclusion The Zurich method uses a pivotal
value of the biometry parameter AC * FL to switch between formulas and corrects
for the errors of the Hadlock formula in fetuses >= 3500 g and those of the Merz
formula in fetuses < 3500 g.
PMID- 26422665
TI - Miniature and Fieldable Mass Spectrometers: Recent Advances.
PMID- 26422669
TI - Doppler Audio Signal Analysis as an Additional Tool in Evaluation of Umbilical
Artery Circulation.
AB - Purpose To investigate the predictive capacity of a new method for sound spectrum
analysis of Doppler signals recorded from the umbilical artery in high-risk
pregnancies. Material and Methods The retrospective study comprised 127 pregnant
women with various pregnancy complications between 23 and 39 gestational weeks.
Umbilical artery blood flow velocity waveforms were recorded with Doppler
ultrasound and characterized by pulsatility index (PI) and blood flow class
(BFC). Doppler audio signals were stored on a digital video recorder and the
sound frequency at the energy level 15 dB below its peak (MAXpeak-15 dB) was
estimated off-line. The prediction of probability for composite adverse pregnancy
outcome (operative delivery for fetal distress, admission to neonatal intensive
care unit, perinatal death) was evaluated using the area under the curve (AUC) of
the receiver operating characteristics (ROC) curve. Results With increasing
umbilical artery BFC, the MAXpeak-15 dB frequencies decreased (p < 0.0001) and
the PI increased (p < 0.0001). The ROC AUCs for adverse outcome for MAXpeak-15 dB
and for PI were 0.842 and 0.836 (p = 0.88), respectively. For the combination of
MAXpeak-15 dB and PI, the corresponding AUC was 0.894, significantly higher than
that of PI (p < 0.03) and of MAXpeak-15 dB (p < 0.05). Conclusion Umbilical
artery Doppler sound spectrum analysis might be a useful supplement to PI in the
clinical evaluation of fetoplacental circulation.
PMID- 26422670
TI - A Cu25 Nanocluster with Partial Cu(0) Character.
AB - Atomically precise copper nanoclusters (NCs) are of immense interest for a
variety of applications, but have remained elusive. Herein, we report the
isolation of a copper NC, [Cu25H22(PPh3)12]Cl (1), from the reaction of Cu(OAc)
and CuCl with Ph2SiH2, in the presence of PPh3. Complex 1 has been fully
characterized, including analysis by X-ray crystallography, XANES, and XPS. In
the solid state, complex 1 is constructed around a Cu13 centered-icosahedron and
formally features partial Cu(0) character. XANES of 1 reveals a Cu K-edge at
8979.6 eV, intermediate between the edge energies of Cu(0) and Cu(I), confirming
our oxidation state assignment. This assignment is further corroborated by
determination of the Auger parameter for 1, which also falls between those
recorded for Cu(0) and Cu(I).
PMID- 26422671
TI - Mg(2+)-dependent facilitation and inactivation of L-type Ca(2+) channels in
guinea pig ventricular myocytes.
AB - This study aimed to investigate the intracellular Mg(2+) regulation of the L-type
Ca(2+) channels in guinea pig ventricular myocytes. By adopting the inside-out
configuration of the patch clamp technique, single channel currents of the L-type
Ca(2+) channels were recorded at different intracellular Mg(2+) concentrations
([Mg(2+)]i). At free [Mg(2+)]i of 0, 10(-9), 10(-7), 10(-5), 10(-3), and 10(-1)
M, 1.4 MUM CaM + 3 mM ATP induced channel activities of 44%, 117%, 202%, 181%,
147%, and 20% of the control activity in cell-attached mode, respectively,
showing a bell-shaped concentration-response relationship. Moreover, the
intracellular Mg(2+) modulated the Ca(2+) channel gating properties, accounting
for alterations in channel activities. These results imply that Mg(2+) has a dual
effect on the L-type Ca(2+) channels: facilitation and inhibition. Lower
[Mg(2+)]i maintains and enhances the basal activity of Ca(2+) channels, whereas
higher [Mg(2+)]i inhibits channel activity. Taken together, our data from the
application of an [Mg(2+)]i series suggest that the dual effect of Mg(2+) upon
the L-type Ca(2+) channels exhibits long open-time dependence.
PMID- 26422672
TI - Mitogen-activated protein kinases regulate expression of neuronal nitric oxide
synthase and neurite outgrowth via non-classical retinoic acid receptor signaling
in human neuroblastoma SH-SY5Y cells.
AB - We have previously shown that retinoic acid receptor (RAR) stimulation by an
agonist Am80 recruits nitric oxide-dependent signaling via increased expression
of neuronal nitric oxide synthase (nNOS) in rat midbrain slice cultures. Using
neuroblastoma SH-SY5Y cells, here we investigated the mechanisms of RAR-induced
nNOS expression, together with relationship between nNOS expression and neurite
outgrowth. Am80 promoted neurite outgrowth, which was attenuated by inhibitors of
phosphoinositide 3-kinase (PI3K; LY294002), c-Jun N-terminal kinase (JNK;
SP600125) and p38 mitogen-activated protein kinase (p38 MAPK; SB203580). A
selective nNOS inhibitor 3-bromo-nitroindazole also suppressed Am80-induced
neurite outgrowth. Am80-induced increase in nNOS protein expression was
attenuated by LY294002, SP600125 and SB203580, whereas increase in nNOS mRNA
expression was attenuated only by LY294002. Am80-induced activation of JNK and
p38 MAPK was blocked by LY294002, suggesting that these kinases acted downstream
of PI3K. We also confirmed that DAX1, a nuclear receptor reported to regulate
nNOS expression, was up-regulated in response to Am80. siRNA-mediated knockdown
of DAX1 abrogated Am80-induced nNOS expression and neurite outgrowth. These
results reveal for the first time that nNOS expression is crucial for RAR
mediated neurite outgrowth, and that non-genomic signaling such as JNK and p38
MAPK is involved in RAR-mediated nNOS expression.
PMID- 26422673
TI - Labor induction in the patient with preterm premature rupture of membranes.
AB - Preterm premature rupture of membranes (PPROM) affects up to one-third of all
preterm births and confers serious maternal risks, including intra-amniotic
infection, and an increased risk of neonatal complications, including respiratory
distress and intraventricular hemorrhage. Management of PPROM is a highly
individualized process that requires an accurate determination of gestational age
and causal factors, as well as the balancing of maternal and fetal risks. In this
review of the existing literature on induction of labor in PPROM, we examine the
differences in appropriate management of patients with early (32 weeks 0 days to
33 weeks 6 days) and near term (34 weeks 0 days to 36 weeks 6 days) PPROM, and
compare the safety and efficacy of available treatment options. This review of
previous research findings provides general guidelines for clinical decision
making and highlights the need for future research on management of PPROM.
PMID- 26422674
TI - Magnetic Field-Controlled Lithium Polysulfide Semiliquid Battery with
Ferrofluidic Properties.
AB - Large-scale energy storage systems are of critical importance for electric grids,
especially with the rapid increasing deployment of intermittent renewable energy
sources such as wind and solar. New cost-effective systems that can deliver high
energy density and efficiency for such storage often involve the flow of redox
molecules and particles. Enhancing the mass and electron transport is critical
for efficient battery operation in these systems. Herein, we report the design
and characterization of a novel proof-of-concept magnetic field-controlled flow
battery using lithium metal-polysulfide semiliquid battery as an example. A
biphasic magnetic solution containing lithium polysulfide and magnetic
nanoparticles is used as catholyte, and lithium metal is used as anode. The
catholyte is composed of two phases of polysulfide with different concentrations,
in which most of the polysulfide molecules and the superparamagnetic iron oxide
nanoparticles can be extracted together to form a high-concentration polysulfide
phase, in close contact with the current collector under the influence of applied
magnetic field. This unique feature can help to maximize the utilization of the
polysulfide and minimize the polysulfide shuttle effect, contributing to enhanced
energy density and Coulombic efficiency. Additionally, owing to the effect of the
superparamagnetic nanoparticles, the concentrated polysulfide phase shows the
behavior of a ferrofluid that is flowable with the control of magnetic field,
which can be used for a hybrid flow battery without the employment of any pumps.
Our innovative design provides new insight for a broad range of flow battery
chemistries and systems.
PMID- 26422675
TI - Cardiovascular Safety of beta3-adrenoceptor Agonists for the Treatment of
Patients with Overactive Bladder Syndrome.
AB - CONTEXT: Mirabegron, the first beta3-adrenoceptor agonist in clinical practice,
is approved for treatment of overactive bladder (OAB) syndrome symptoms. Because
beta3-adrenoceptors are expressed in cardiovascular (CV) tissues, there are
concerns that OAB treatment with beta3-adrenoceptor agonists may affect the heart
and vasculature. OBJECTIVE: To provide a summary of CV effects of beta3
adrenoceptor agonists in clinical studies. EVIDENCE ACQUISITION: A systematic
literature search from inception until November 2014 was performed on studies in
PubMed and Medline. EVIDENCE SYNTHESIS: Twenty papers, published between 1994 and
2014, were identified: mirabegron (16), solabegron (2), AK-677 (1), and BRL35135
(1). More detailed CV data from mirabegron studies were available in online
regulatory documents filed with the US Food and Drug Administration and the UK
National Institute for Health and Care Excellence. CONCLUSIONS: The CV safety of
mirabegron appears to be acceptable at therapeutic doses and comparable with that
of antimuscarinic agents, currently first-line therapy for OAB. PATIENT SUMMARY:
In this review we looked at the cardiovascular (CV) effects of beta3-adrenoceptor
agonists used for the treatment of overactive bladder (OAB). The CV safety of
mirabegron (the only clinically approved beta3-adrenoceptor agonist) appears to
be acceptable at therapeutic doses and comparable with that of antimuscarinic
agents, the current first-line therapy for OAB.
PMID- 26422676
TI - Addition of Docetaxel to Androgen Deprivation Therapy for Patients with Hormone
sensitive Metastatic Prostate Cancer: A Systematic Review and Meta-analysis.
AB - CONTEXT: Several randomized clinical trials (RCTs) have recently tested the early
addition of docetaxel to androgen deprivation therapy (ADT) in hormone-sensitive
metastatic prostate cancer (PCa). OBJECTIVE: To perform a systematic review and
meta-analysis of RCTs evaluating the combination of docetaxel and ADT in hormone
sensitive metastatic PCa. The primary end point was overall survival (OS).
Secondary end point was progression-free survival. Exploratory subgroup analysis
according to high-volume versus low-volume disease was performed. EVIDENCE
ACQUISITION: A systematic review of PubMed/Medline, Embase, and the proceedings
of major international meetings was performed in June 2015 and updated in August
2015. Three trials were selected for inclusion. EVIDENCE SYNTHESIS: Overall, 2951
patients were included in the three trials. Two trials enrolled only metastatic
patients; in the third trial, 61% were metastatic. A total of 2262 patients (951
docetaxel and ADT; 1311 ADT alone) were metastatic. Most patients had a good
performance status. In metastatic patients, the addition of docetaxel was
associated with improved OS (hazard ratio [HR]: 0.73; 95% confidence interval
[CI], 0.60-0.90; p=0.002), with nonsignificant heterogeneity among the three
trials. Considering the whole study population (2951 patients), the addition of
docetaxel was associated with a similar OS improvement (HR: 0.74; 95% CI, 0.61
0.91; p=0.003). Although with limited statistical power, no significant
interaction was demonstrated between the addition of docetaxel and the high or
low volume of disease (p=0.5). The addition of docetaxel was associated with
improvement in progression-free survival (metastatic patients: HR: 0.63; 95% CI,
0.57-0.70; p<0.001). CONCLUSIONS: This meta-analysis shows a significant OS
benefit from concomitant administration of docetaxel and ADT in patients with
metastatic hormone-sensitive PCa. PATIENT SUMMARY: We synthesized the evidence
available about the early administration of docetaxel in patients starting
hormonal treatment for metastatic prostate cancer. Based on the results of this
meta-analysis, we believe the combination of chemotherapy and hormonal treatment
should be considered in fit patients.
PMID- 26422677
TI - Chronic lead poisoning magnifies bone detrimental effects in an ovariectomized
rat model of postmenopausal osteoporosis.
AB - Lead (Pb) is a persistent environmental contaminant that is mainly stored in
bones being an important source of endogenous lead exposure during periods of
increased bone resorption as occurs in menopause. As no evidence exists of which
bone biomechanical properties are impaired in those elderly women who had been
exposed to Pb during their lifetime, the aim of the present study is to discern
whether chronic lead poisoning magnifies the deterioration of bone biology that
occurs in later stages of life. We investigated the effect of Pb in the femora of
ovariectomized (OVX) female Wistar rats who had been intoxicated with 1000 ppm of
Pb acetate in drinking water for 8 months. Structural properties were determined
using a three-point bending mechanical test, and geometrical and material
properties were evaluated after obtaining the load/deformation curve. Areal Bone
Mineral Density (BMD) was estimated using a bone densitometer. Femoral
histomorphometry was carried out on slices dyed with H&E (Hematoxylin and Eosin).
Pb and OVX decreased all structural properties with a higher effect when both
treatments were applied together. Medullar and cortical area of femurs under OVX
increased, allowing the bone to accommodate its architecture, which was not
observed under Pb intoxication. Pb and OVX significantly decreased BMD, showing
lead treated ovariectomized rats (PbOVX) animals the lowest BMD levels.
Trabecular bone volume per total volume (BV/TV%) was decreased in OVX and PbOVX
animals in 54% compared to the control animals (p<0.001). Pb femurs also showed
28% less trabeculae than the control (p<0.05). We demonstrated that Pb
intoxication magnifies the impairment in bone biomechanics of OVX rats with a
consequent enhancement of the risk of fracture. These results enable the
discussion of the detrimental effects of lead intoxication in bone biology in
elderly women.
PMID- 26422678
TI - A Clinical Tool for the Prediction of Venous Thromboembolism in Pediatric Trauma
Patients.
AB - IMPORTANCE: Although rare, the incidence of venous thromboembolism (VTE) in
pediatric trauma patients is increasing, and the consequences of VTE in children
are significant. Studies have demonstrated increasing VTE risk in older pediatric
trauma patients and improved VTE rates with institutional interventions. While
national evidence-based guidelines for VTE screening and prevention are in place
for adults, none exist for pediatric patients, to our knowledge. OBJECTIVES: To
develop a risk prediction calculator for VTE in children admitted to the hospital
after traumatic injury to assist efforts in developing screening and prophylaxis
guidelines for this population. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
review of 536,423 pediatric patients 0 to 17 years old using the National Trauma
Data Bank from January 1, 2007, to December 31, 2012. Five mixed-effects logistic
regression models of varying complexity were fit on a training data set. Model
validity was determined by comparison of the area under the receiver operating
characteristic curve (AUROC) for the training and validation data sets from the
original model fit. A clinical tool to predict the risk of VTE based on
individual patient clinical characteristics was developed from the optimal model.
MAIN OUTCOME AND MEASURE: Diagnosis of VTE during hospital admission. RESULTS:
Venous thromboembolism was diagnosed in 1141 of 536,423 children (overall rate,
0.2%). The AUROCs in the training data set were high (range, 0.873-0.946) for
each model, with minimal AUROC attenuation in the validation data set. A
prediction tool was developed from a model that achieved a balance of high
performance (AUROCs, 0.945 and 0.932 in the training and validation data sets,
respectively; P = .048) and parsimony. Points are assigned to each variable
considered (Glasgow Coma Scale score, age, sex, intensive care unit admission,
intubation, transfusion of blood products, central venous catheter placement,
presence of pelvic or lower extremity fractures, and major surgery), and the
points total is converted to a VTE risk score. The predicted risk of VTE ranged
from 0.0% to 14.4%. CONCLUSIONS AND RELEVANCE: We developed a simple clinical
tool to predict the risk of developing VTE in pediatric trauma patients. It is
based on a model created using a large national database and was internally
validated. The clinical tool requires external validation but provides an initial
step toward the development of the specific VTE protocols for pediatric trauma
patients.
PMID- 26422679
TI - Proximal bronchial balloon dilation for embedded distal airway foreign bodies.
PMID- 26422680
TI - Efficacy of entecavir therapy for hepatitis B e-antigen positive chronic
hepatitis B patients with prior exposure to interferon or nucleoside/nucleotide
analogues.
PMID- 26422681
TI - Life-Threatening Contraceptive-Related Pulmonary Embolism in a 14-Year-Old Girl
with Hereditary Thrombophilia.
AB - BACKGROUND: The prothrombotic effect of combined oral contraceptives (COCs) is
well-established, with a 3-6-fold increased risk of VTE compared to non-users.
When initiation of COCs is considered, it is therefore of paramount importance to
carefully evaluate all other potential risk factors for VTE. Based on a case of
life-threatening COC-associated pulmonary embolism in a girl heterozygous for the
prothrombin G20210A mutation and with a family history of thrombotic disease, we
discuss the importance of assessing not just the genotype but also the phenotype
when considering initiation of COCs in patients with thrombophilia. CASE REPORT:
A 14-year-old girl presented with acute onset of chest pain and dyspnea followed
by syncope. She was hypoxic and hemodynamically compromised at admission.
Computed tomography pulmonary angiography revealed a large central "saddle"
pulmonary embolism causing nearly total occlusion of the right pulmonary artery,
and several minor peripheral embolisms bilaterally. She was successfully treated
with thrombolysis (alteplase) followed by aPTT-adjusted heparin infusion until
adequate anticoagulation with warfarin was achieved. Two years earlier, the
patient had been found heterozygote for the prothrombin G20210A mutation, and 9
months before admission she had initiated use of second-generation COCs.
CONCLUSIONS: Hereditary thrombophilia and a family history of early-onset venous
thromboembolism (VTE) each pose an increased risk of VTE and should be considered
as separate, irreversible risk factors. Other contraceptive methods should be
used when treatment with COCs is expected to result in an unacceptable high risk
of VTE.
PMID- 26422682
TI - Sex Steroid Hormone Levels May Not Explain Gender Differences in Development of
Nephrolithiasis.
AB - OBJECTIVES: To determine whether serum sex steroid hormone levels, or the
subsequent change in those levels over time, represent a risk factor for the
development of nephrolithiasis in men. METHODS: We retrospectively identified
patients participating in a long-term cohort study (Rochester Epidemiology
Project) in Olmsted County, Minnesota. Patients had previously undergone baseline
detailed clinical examination and sex steroid hormone studies, including
estradiol, testosterone, and bioavailable testosterone. Patients were followed on
a biennial basis. Records were then reviewed to assess for formation of
nephrolithiasis. RESULTS: We identified 684 patients, with a median follow-up for
stone formation of 12.8 years. All 684 patients had measurement of testosterone,
of which 78.9% were in normal range. Five hundred eighteen men had baseline-free
testosterone, of whom 88.6% were normal. Three hundred seventy-one patients had
baseline estradiol, of whom 88.7% were normal. One hundred two men (14.9%) were
found to have stones, with 61 of those (59.8%) occurring before first hormone
measurement and 41 (40.2%) occurring after. On multivariate analysis, there was
no significant association of serum hormones with nephrolithiasis, although a
trend toward higher baseline testosterone and stones was seen (odds ratio [OR]
1.29; 95% confidence intervals [CI] 0.71, 2.33). Using a time-to-event for
incident stone formation, we found no significant association of baseline
hormones or percentage change in hormone levels over time with risk of stones.
CONCLUSION: We found no significant association of sex steroid hormone levels
with the risk of nephrolithiasis formation in men, although a weak trend toward
an increased risk with elevated testosterone was seen.
PMID- 26422683
TI - High-visfatin levels in women with polycystic ovary syndrome: evidence from a
meta-analysis.
AB - OBJECTIVE: Previous studies regarding visfatin levels in women with polycystic
ovary syndrome (PCOS) showed conflicting results. To evaluate the visfatin levels
in PCOS, a meta-analysis was performed. METHODS: A comprehensive literature
search of eligible studies in Embase, Pubmed and the Cochrane Library was
undertaken through November 2014. Standardized mean differences (SMDs) with 95%
confidence intervals (CIs) were calculated to estimate the strength of the
association. RESULTS: A total of 1341 subjects (695 cases and 646 controls) were
included in this meta-analysis. The pooled analysis results indicated that the
visfatin levels were significantly higher in PCOS patients than that of controls
(SMD = 1.19, 95% CI 0.77-1.60, p = 0.000). The results from stratified analysis
and univariate analysis suggested that high-visfatin levels were not related to
body mass index (BMI), insulin resistance (IR) and total testosterone ratio.
Significant heterogeneity was observed in all analysis. CONCLUSION: Our results
indicate that high-circulating visfatin level is an intrinsic characteristic of
PCOS, which suggests visfatin could be a potential biomarker for PCOS.
PMID- 26422684
TI - Habitat Effects on the Breeding Performance of Three Forest-Dwelling Hawks.
AB - Habitat loss causes population declines, but the mechanisms are rarely known. In
the European Boreal Zone, loss of old forest due to intensive forestry is
suspected to cause declines in forest-dwelling raptors by reducing their breeding
performance. We studied the boreal breeding habitat and habitat-associated
breeding performance of the northern goshawk (Accipiter gentilis), common buzzard
(Buteo buteo) and European honey buzzard (Pernis apivorus). We combined long-term
Finnish bird-of-prey data with multi-source national forest inventory data at
various distances (100-4000 m) around the hawk nests. We found that breeding
success of the goshawk was best explained by the habitat within a 2000-m radius
around the nests; breeding was more successful with increasing proportions of old
spruce forest and water, and decreasing proportions of young thinning forest.
None of the habitat variables affected significantly the breeding success of the
common buzzard or the honey buzzard, or the brood size of any of the species. The
amount of old spruce forest decreased both around goshawk and common buzzard
nests and throughout southern Finland in 1992-2010. In contrast, the area of
young forest increased in southern Finland but not around hawk nests. We
emphasize the importance of studying habitats at several spatial and temporal
scales to determine the relevant species-specific scale and to detect
environmental changes. Further effort is needed to reconcile the socioeconomic
and ecological functions of forests and habitat requirements of old forest
specialists.
PMID- 26422685
TI - Effective Linkages of Continuum of Care for Improving Neonatal, Perinatal, and
Maternal Mortality: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Continuum of care has the potential to improve maternal, newborn, and
child health (MNCH) by ensuring care for mothers and children. Continuum of care
in MNCH is widely accepted as comprising sequential time (from pre-pregnancy to
motherhood and childhood) and space dimensions (from community-family care to
clinical care). However, it is unclear which linkages of care could have a
greater effect on MNCH outcomes. The objective of the present study is to assess
the effectiveness of different continuum of care linkages for reducing neonatal,
perinatal, and maternal mortality in low- and middle-income countries. METHODS:
We searched for randomized and quasi-randomized controlled trials that addressed
two or more linkages of continuum of care and attempted to increase mothers'
uptake of antenatal care, skilled birth attendance, and postnatal care. The
outcome variables were neonatal, perinatal, and maternal mortality. RESULTS: Out
of the 7,142 retrieved articles, we selected 19 as eligible for the final
analysis. Of these studies, 13 used packages of intervention that linked
antenatal care, skilled birth attendance, and postnatal care. One study each used
packages that linked antenatal care and skilled birth attendance or skilled birth
attendance and postnatal care. Four studies used an intervention package that
linked antenatal care and postnatal care. Among the packages that linked
antenatal care, skilled birth attendance, and postnatal care, a significant
reduction was observed in combined neonatal, perinatal, and maternal mortality
risks (RR 0.83; 95% CI 0.77 to 0.89, I2 79%). Furthermore, this linkage reduced
combined neonatal, perinatal, and maternal mortality when integrating the
continuum of care space dimension (RR 0.85; 95% CI 0.77 to 0.93, I2 81%).
CONCLUSIONS: Our review suggests that continuous uptake of antenatal care,
skilled birth attendance, and postnatal care is necessary to improve MNCH
outcomes in low- and middle-income countries. The review was conclusive for the
reduction of neonatal and perinatal deaths. Although maternal deaths were not
significantly reduced, composite measures of all mortality were. Thus, the
evidence is sufficient to scale up this intervention package for the improvement
of MNCH outcomes.
PMID- 26422686
TI - Thermodynamics of Rev-RNA interactions in HIV-1 Rev-RRE assembly.
AB - The HIV-1 protein Rev facilitates the nuclear export of intron-containing viral
mRNAs by recognizing a structured RNA site, the Rev-response-element (RRE),
contained in an intron. Rev assembles as a homo-oligomer on the RRE using its
alpha-helical arginine-rich-motif (ARM) for RNA recognition. One unique feature
of this assembly is the repeated use of the ARM from individual Rev subunits to
contact distinct parts of the RRE in different binding modes. How the individual
interactions differ and how they contribute toward forming a functional complex
is poorly understood. Here we examine the thermodynamics of Rev-ARM peptide
binding to two sites, RRE stem IIB, the high-affinity site that nucleates Rev
assembly, and stem IA, a potential intermediate site during assembly, using NMR
spectroscopy and isothermal titration calorimetry (ITC). NMR data indicate that
the Rev-IIB complex forms a stable interface, whereas the Rev-IA interface is
highly dynamic. ITC studies show that both interactions are enthalpy-driven, with
binding to IIB being 20-30 fold tighter than to IA. Salt-dependent decreases in
affinity were similar at both sites and predominantly enthalpic in nature,
reflecting the roles of electrostatic interactions with arginines. However, the
two interactions display strikingly different partitioning between enthalpy and
entropy components, correlating well with the NMR observations. Our results
illustrate how the variation in binding modes to different RRE target sites may
influence the stability or order of Rev-RRE assembly and disassembly, and
consequently its function.
PMID- 26422687
TI - How Can Childbirth Care for the Rural Poor Be Improved? A Contribution from
Spatial Modelling in Rural Tanzania.
AB - INTRODUCTION: Maternal and perinatal mortality remain a challenge in resource
limited countries, particularly among the rural poor. To save lives at birth
health facility delivery is recommended. However, increasing coverage of
institutional deliveries may not translate into mortality reduction if shortage
of qualified staff and lack of enabling working conditions affect quality of
services. In Tanzania childbirth care is available in all facilities; yet
maternal and newborn mortality are high. The study aimed to assess in a high
facility density rural context whether a health system organization with fewer
delivery sites is feasible in terms of population access. METHODS: Data on health
facilities' location, staffing and delivery caseload were examined in Ludewa and
Iringa Districts, Southern Tanzania. Geospatial raster and network analysis were
performed to estimate access to obstetric services in walking time. The present
geographical accessibility was compared to a theoretical scenario with a 40%
reduction of delivery sites. RESULTS: About half of first-line health facilities
had insufficient staff to offer full-time obstetric services (45.7% in Iringa and
78.8% in Ludewa District). Yearly delivery caseload at first-line health
facilities was low, with less than 100 deliveries in 48/70 and 43/52 facilities
in Iringa and Ludewa District respectively. Wide geographical overlaps of
facility catchment areas were observed. In Iringa 54% of the population was
within 1-hour walking distance from the nearest facility and 87.8% within 2
hours, in Ludewa, the percentages were 39.9% and 82.3%. With a 40% reduction of
delivery sites, approximately 80% of population will still be within 2 hours'
walking time. CONCLUSIONS: Our findings from spatial modelling in a high facility
density context indicate that reducing delivery sites by 40% will decrease
population access within 2 hours by 7%. Focused efforts on fewer delivery sites
might assist strengthening delivery services in resource-limited settings.
PMID- 26422689
TI - The GroEL-GroES Chaperonin Machine: A Nano-Cage for Protein Folding.
AB - The bacterial chaperonin GroEL and its cofactor GroES constitute the paradigmatic
molecular machine of protein folding. GroEL is a large double-ring cylinder with
ATPase activity that binds non-native substrate protein (SP) via hydrophobic
residues exposed towards the ring center. Binding of the lid-shaped GroES to
GroEL displaces the bound protein into an enlarged chamber, allowing folding to
occur unimpaired by aggregation. GroES and SP undergo cycles of binding and
release, regulated allosterically by the GroEL ATPase. Recent structural and
functional studies are providing insights into how the physical environment of
the chaperonin cage actively promotes protein folding, in addition to preventing
aggregation. Here, we review different models of chaperonin action and discuss
issues of current debate.
PMID- 26422688
TI - [Smoking prevalence in hospital workers: meta-analysis in 45 Catalan hospitals].
AB - OBJECTIVE: To estimate the prevalence of smoking in workers from hospitals within
the Catalan Network for Smoke-free hospitals from 2009 to 2012 according to
workers' sociodemographic characteristics and the type of hospital. METHOD: A
meta-analysis was performed of prevalence surveys from representative samples of
workers from 45 hospitals. The combined prevalence for all hospitals was
calculated using a regression model with a random effects model weighted by
sample size. RESULTS: The overall prevalence of smoking was 28.1% (95%CI: 26.1 to
30.0%) with a maximum and minimum of 40.3% and 19.1%, respectively. The health
professionals with the lowest prevalence of smoking were physicians (16.4%;
95%CI: 12.9 to 19.9) and nurses (25.4%; 95%CI 21.6 to 29.2). CONCLUSION: The
prevalence of smoking in hospital health workers was lower than in the general
population of working age. Physicians were the group with the lowest smoking
prevalence. Smoking cessation should be promoted among other professional groups.
PMID- 26422690
TI - Demethylation of Circulating Estrogen Receptor Alpha Gene in Cerebral Ischemic
Stroke.
AB - BACKGROUND: Estrogen is involved in neuron plasticity and can promote neuronal
survival in stroke. Its actions are mostly exerted via estrogen receptor alpha
(ERalpha). Previous animal studies have shown that ERalpha is upregulated by DNA
demethylation following ischemic injury. This study investigated the methylation
levels in the ERalpha promoter in the peripheral blood of ischemic stroke
patients. METHODS: The study included 201 ischemic stroke patients, and 217 age-
and sex-comparable healthy controls. The quantitative methylation level in the 14
CpG sites of the ERalpha promoter was measured by pyrosequencing in each
participant. Multivariate regression model was used to adjust for stroke
traditional risk factors. Stroke subtypes and sex-specific analysis were also
conducted. RESULTS: The results demonstrated that the stroke cases had a lower
ERalpha methylation level than controls in all 14 CpG sites, and site 13 and site
14 had significant adjusted p-values of 0.035 and 0.026, respectively. Stroke
subtypes analysis showed that large-artery atherosclerosis and cardio-embolic
subtypes had significantly lower methylation levels than the healthy controls at
CpG site 5, site 9, site 12, site 13 and site 14 with adjusted p = 0.039, 0.009,
0.025, 0.046 and 0.027 respectively. However, the methylation level for the
patients with small vessel subtype was not significant. We combined the
methylation data from the above five sites for further sex-specific analysis. The
results showed that the significant association only existed in women (adjusted p
= 0.011), but not in men (adjusted p = 0.300). CONCLUSIONS: Female stroke cases
have lower ERalpha methylation levels than those in the controls, especially in
large-artery and cardio-embolic stroke subtypes. The study implies that women
suffering from ischemic stroke of specific subtype may undergo different
protective mechanisms to reduce the brain injury.
PMID- 26422692
TI - Wingspan Stenting for Severe Symptomatic Intracranial Atherosclerotic Stenosis in
433 Patients Treated at a Single Medical Center.
AB - PURPOSE: To investigate the safety and outcome of intracranial stenting for
intracranial atherosclerotic stenosis (IAS). MATERIALS AND METHODS: Between July
2007 and April 2013, 433 consecutive patients with IAS > 70% underwent
intracranial Wingspan stenting, and the data were prospectively analyzed.
RESULTS: Intracranial stenting was successful in 429 patients (99.1%), and the
mean stenosis rate was improved from prestenting (82.3 +/- 7.6)% to poststenting
(16.6 +/- 6.6)%. During the 30-day perioperative period, 29 patients (6.7%)
developed stroke. The total perioperative stroke rate was significantly (P <
0.01) higher in the basilar artery area than in others, whereas the hemorrhagic
stroke rate was significantly (P < 0.05) greater in the middle cerebral artery
area than in others. The experience accumulation stage (13%) had a significantly
(P < 0.05) higher stroke rate than the technical maturation stage (4.8%).
Clinical follow-up 6-69 months poststenting revealed ipsilateral stroke in 20
patients (5.5%). The one- and two-year cumulative stroke rates were 9.5% and
11.5%, respectively; the two-year cumulative stroke rate was significantly (P <
0.05) greater in the experience accumulation stage (18.8%) than in the technical
maturation stage (9.1%). CONCLUSION: Wingspan stenting for intracranial
atherosclerotic stenosis is safe and the long-term stroke rate after stenting is
low in a Chinese subpopulation.
PMID- 26422693
TI - Double-Door or "French-Door" Cervical Laminoplasty.
AB - PURPOSE: Cervical spondylotic myelopathy (CSM) is a condition resulting from
cervical stenosis. Manifestations of CSM include paresthesia in the extremities,
loss of fine motor skills, balance problems, and bowel and bladder dysfunction in
advanced disease. Laminoplasty is one surgical treatment option. The goal of
laminoplasty is to reposition the laminae to expand the spinal canal, allowing
the spinal cord to migrate posteriorly. There are various laminoplasty
techniques; the main ones being open-door laminoplasty and double-door
laminoplasty. This manuscript demonstrates a double-door laminoplasty otherwise
known as a "French-door" laminoplasty discusses the indications and outcomes of
this procedure. METHODS: The double-door laminoplasty creates an opening in the
midline of the spinous processes and a symmetrical expansion with hinges on both
laminae. Bilateral troughs are drilled on each laminae using a bur, and opened
liked a French-door, allowing the spinal cord to move posteriorly in the enlarged
spinal canal. The space between the gapped laminae are then stabilized by
allograft. RESULTS: This manuscript presents the case of a 56-year-old man with
CSM caused by multilevel cervical stenosis. The patient had classic signs and
symptoms of CSM including problems with fine motor skills and walking difficulty.
The video demonstrates the spinal cord decompression achieved with the French
door technique from C4 to C6 with a dome laminectomy at C3. CONCLUSIONS: There
are many surgical treatments for cervical stenosis including anterior cervical
discectomy and fusions and posterior procedures such as laminoplasty or
laminectomy and fusion. The indications and technical pearls for French-door
laminoplasty are presented as an effective option for the treatment of multilevel
cervical stenosis.
PMID- 26422691
TI - Evidence that beta7 Integrin Regulates Hematopoietic Stem Cell Homing and
Engraftment Through Interaction with MAdCAM-1.
AB - alpha4beta7 integrin is a cell adhesion receptor that is crucial for the
migration of hematopoietic progenitors and mature effector cells in the
periphery, but its role in adult hematopoiesis is controversial. We identified a
subset of hematopoietic stem cells (HSCs) in the bone marrow (BM) that expressed
beta7 integrin. These beta7(+) HSCs were capable of multilineage, long-term
reconstitution and had an inherent competitive advantage over beta7(-) HSCs. On
the other hand, HSCs that lacked beta7 integrin (beta7KO) had reduced engraftment
potential. Interestingly, quantitative RT-PCR and flow cytometry revealed that
beta7KO HSCs expressed lower levels of the chemokine receptor CXCR4. Accordingly,
beta7KO HSCs exhibited impaired migration abilities in vitro and BM homing
capabilities in vivo. Lethal irradiation induced expression of the alpha4beta7
integrin ligand-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on BM
endothelial cells. Moreover, blocking MAdCAM-1 reduced the homing of HSCs and
impaired the survival of recipient mice. Altogether, these data indicate that
beta7 integrin, when expressed by HSCs, interacted with its endothelial ligand
MAdCAM-1 in the BM microenvironment, thereby promoting HSC homing and
engraftment.
PMID- 26422694
TI - Tracking Public Beliefs About Anthropogenic Climate Change.
AB - A simple question about climate change, with one choice designed to match
consensus statements by scientists, was asked on 35 US nationwide, single-state
or regional surveys from 2010 to 2015. Analysis of these data (over 28,000
interviews) yields robust and exceptionally well replicated findings on public
beliefs about anthropogenic climate change, including regional variations, change
over time, demographic bases, and the interacting effects of respondent education
and political views. We find that more than half of the US public accepts the
scientific consensus that climate change is happening now, caused mainly by human
activities. A sizable, politically opposite minority (about 30 to 40%) concede
the fact of climate change, but believe it has mainly natural causes. Few (about
10 to 15%) say they believe climate is not changing, or express no opinion. The
overall proportions appear relatively stable nationwide, but exhibit place-to
place variations. Detailed analysis of 21 consecutive surveys within one fairly
representative state (New Hampshire) finds a mild but statistically significant
rise in agreement with the scientific consensus over 2010-2015. Effects from
daily temperature are detectable but minor. Hurricane Sandy, which brushed New
Hampshire but caused no disaster there, shows no lasting impact on that state's
time series-suggesting that non-immediate weather disasters have limited effects.
In all datasets political orientation dominates among individual-level predictors
of climate beliefs, moderating the otherwise positive effects from education.
Acceptance of anthropogenic climate change rises with education among Democrats
and Independents, but not so among Republicans. The continuing series of surveys
provides a baseline for tracking how future scientific, political, socioeconomic
or climate developments impact public acceptance of the scientific consensus.
PMID- 26422696
TI - Tin Nanodots Encapsulated in Porous Nitrogen-Doped Carbon Nanofibers as a Free
Standing Anode for Advanced Sodium-Ion Batteries.
AB - Ultrasmall Sn nanodots (1-2 nm) are homogeneously encapsulated in porous N-doped
carbon nanofibers using a simple and scalable electrospinning method. The
composite nanofibers weave into flexible free-standing membrane and can be
directly used as binder- and current collector-free anode for Na-ion batteries,
exhibiting excellent electrochemical performance with high reversible capacity,
exceptional rate capability, and ultralong cycle life.
PMID- 26422697
TI - Thin-dielectric-layer engineering for 3D nanostructure integration using an
innovative planarization approach.
AB - Three-dimensional (3D) nanostructures are emerging as promising building blocks
for a large spectrum of applications. One critical issue in integration regards
mastering the thin, flat, and chemically stable insulating layer that must be
implemented on the nanostructure network in order to build striking nano
architectures. In this letter, we report an innovative method for nanoscale
planarization on 3D nanostructures by using hydrogen silesquioxane as a spin-on
glass (SOG) dielectric material. To decouple the thickness of the final layer
from the height of the nanostructure, we propose to embed the nanowire network in
the insulator layer by exploiting the planarizing properties of the SOG approach.
To achieve the desired dielectric thickness, the structure is chemically etched
back with a highly diluted solution to control the etch rate precisely. The
roughness of the top surface was less than 2 nm. There were no surface defects
and the planarity was excellent, even in the vicinity of the nanowires. This
newly developed process was used to realize a multilevel stack architecture with
sub-deca-nanometer-range layer thickness.
PMID- 26422695
TI - MicroRNA expression profiling in children with different asthma phenotypes.
AB - An improved understanding of the molecular mechanisms in asthma through exploring
the role of microRNAs may offer promise to reveal new approaches for primary
prevention and identification of new therapeutic targets in childhood asthma. The
primary goal of this study is to identify the microRNAs that play a role in the
pathogenesis of asthma in pediatric age group. The secondary goal is to analyze
these microRNAs according to the asthma phenotype, atopic status, and severity of
the disease exacerbation. To our knowledge, this is the first research project in
the literature which studies the relationship between microRNA expression and the
severity of childhood asthma. One hundred children between 6 and 18 years old
with a diagnosis of asthma, and 100 age-matched healthy children were enrolled in
this study, and the analyses of microRNA expression profiles were performed in
the Medical Genetics Laboratories of Ege University between November 2009 and
June 2010. The expression of 10 microRNAs were shown to be higher in patients
with more severe asthma, and the expression of these microRNAs were also found to
be higher in patients who present with more severe acute asthma exacerbation
symptoms (P < 0.001). Also, five microRNAs were found to be expressed more than
twofold in allergic patients when compared to non-allergic participants (P
<0.001). Asthma is one of the best examples of complex genetic diseases, and
further studies, which will investigate the relationship between these microRNA's
and their target genes, are needed to learn more about the specific roles of
microRNAs in respiratory diseases. Pediatr Pulmonol. 2016;51:582-587. (c) 2015
Wiley Periodicals, Inc.
PMID- 26422698
TI - Effect of Risk of Bias on the Effect Size of Meta-Analytic Estimates in
Randomized Controlled Trials in Periodontology and Implant Dentistry.
AB - BACKGROUND: Risk of bias (ROB) may threaten the internal validity of a clinical
trial by distorting the magnitude of treatment effect estimates, although some
conflicting information on this assumption exists. OBJECTIVE: The objective of
this study was evaluate the effect of ROB on the magnitude of treatment effect
estimates in randomized controlled trials (RCTs) in periodontology and implant
dentistry. METHODS: A search for Cochrane systematic reviews (SRs), including
meta-analyses of RCTs published in periodontology and implant dentistry fields,
was performed in the Cochrane Library in September 2014. Random-effect meta
analyses were performed by grouping RCTs with different levels of ROBs in three
domains (sequence generation, allocation concealment, and blinding of outcome
assessment). To increase power and precision, only SRs with meta-analyses
including at least 10 RCTs were included. Meta-regression was performed to
investigate the association between ROB characteristics and the magnitudes of
intervention effects in the meta-analyses. RESULTS: Of the 24 initially screened
SRs, 21 SRs were excluded because they did not include at least 10 RCTs in the
meta-analyses. Three SRs (two from periodontology field) generated information
for conducting 27 meta-analyses. Meta-regression did not reveal significant
differences in the relationship of the ROB level with the size of treatment
effect estimates, although a trend for inflated estimates was observed in domains
with unclear ROBs. CONCLUSION: In this sample of RCTs, high and (mainly) unclear
risks of selection and detection biases did not seem to influence the size of
treatment effect estimates, although several confounders might have influenced
the strength of the association.
PMID- 26422699
TI - Low-energy structures of benzene clusters with a novel accurate potential
surface.
AB - The benzene-benzene (Bz-Bz) interaction is present in several chemical systems
and it is known to be crucial in understanding the specificity of important
biological phenomena. In this work, we propose a novel Bz-Bz analytical potential
energy surface which is fine-tuned on accurate ab initio calculations in order to
improve its reliability. Once the Bz-Bz interaction is modeled, an analytical
function for the energy of the Bzn clusters may be obtained by summing up over
all pair potentials. We apply an evolutionary algorithm (EA) to discover the
lowest-energy structures of Bzn clusters (for n=2-25), and the results are
compared with previous global optimization studies where different potential
functions were employed. Besides the global minimum, the EA also gives the
structures of other low-lying isomers ranked by the corresponding energy.
Additional ab initio calculations are carried out for the low-lying isomers of
Bz3 and Bz4 clusters, and the global minimum is confirmed as the most stable
structure for both sizes. Finally, a detailed analysis of the low-energy isomers
of the n = 13 and 19 magic-number clusters is performed. The two lowest-energy
Bz13 isomers show S6 and C3 symmetry, respectively, which is compatible with the
experimental results available in the literature. The Bz19 structures reported
here are all non-symmetric, showing two central Bz molecules surrounded by 12
nearest-neighbor monomers in the case of the five lowest-energy structures.
PMID- 26422700
TI - High incidence of metachronous advanced adenoma and cancer after endoscopic
resection of colon polyps >=20 mm in size.
AB - BACKGROUND AND AIM: There are limited studies on incidence rates of metachronous
neoplastic lesions after resecting large colorectal polyps. In the present study,
we analyzed metachronous lesions after endoscopic resection of colorectal polyps
>=20 mm in size. METHODS: We retrospectively analyzed consecutive patients who
underwent endoscopic resection of polyps from 2006 to 2013 at two affiliated
hospitals. All patients underwent at least two total colonoscopies before follow
up to ensure minimal missed polyps. Only patients who had follow-up colonoscopy
annually after resection were recruited. We separated patients according to size
of polyp resected; there were 239 patients in the >=20-mm group and 330 patients
in the <20-mm group. Clinical characteristics and cumulative rates of
metachronous advanced adenoma and cancer in both groups were analyzed. Advanced
adenoma was defined as a neoplastic lesion >=10 mm in size and adenoma with a
villous component. RESULTS: Cumulative rate of development of metachronous
advanced adenoma and cancer in the >=20-mm group was significantly higher than in
the <20-mm group (22.9% vs. 9.5%, P < 0.001) at 36 months. There was also more
development of small polyps 5-9 mm in the >=20-mm group than in the <20-mm group
(45.2% vs. 28.8%, P < 0.001). With respect to metachronous lesions, there were
more right-sided colonic lesions in the >=20-mm group than in the <20-mm group
(78.8% vs. 50.0%, P = 0.015). CONCLUSION: High incidence rates of development of
metachronous neoplastic lesions were detected after resection of colorectal
polyps >=20 mm in size.
PMID- 26422702
TI - Motivating contributions to online forums: can locus of control moderate the
effects of interface cues?
AB - In an effort to encourage users to participate rather than lurk, online health
forums provide authority badges (e.g., guru) to frequent contributors and
popularity indicators (e.g., number of views) to their postings. Studies have
shown the latter to be more effective, implying that bulletin-board users are
motivated by external validation of their contributions. However, no
consideration has yet been given to individual differences in the influence of
such popularity indicators. Personality psychology suggests that individuals with
external, rather than internal, locus of control are more likely to be other
directed and therefore more likely to be motivated by interface cues showing the
bandwagon effect of their online posts. We investigate this hypothesis by
analyzing data from a 2 (high vs. low authority cue) * 2 (strong vs. weak
bandwagon cue) experiment with an online health community. Results show that
strong bandwagon cues promote sense of community among users with internal,
rather than external, locus of control. When bandwagon cues are weak, bestowal of
high authority serves to heighten their sense of agency. Contrary to prediction,
weak bandwagon cues appear to promote sense of community and sense of agency
among those with external locus of control. Theoretical and practical
implications are discussed.
PMID- 26422701
TI - ANXIOUS AND AGGRESSIVE: THE CO-OCCURRENCE OF IED WITH ANXIETY DISORDERS.
AB - BACKGROUND: Evidence suggests that impulsive aggression and explosive anger are
common among individuals with anxiety disorders; yet, the influence of
intermittent explosive disorder (IED) on the onset, course, consequences, and
patterns of comorbidity among those with anxiety disorders is unknown. METHODS:
Data were drawn from the National Comorbidity Survey Replication (N = 9,282) and
Adolescent Supplement (N = 9,632), nationally representative surveys conducted
between 2001 and 2004. Diagnoses were based on structured lay-administered
interviews. Lifetime diagnoses were assessed with structured instruments.
Outcomes included comorbidity, functional and role impairment, and treatment
utilization. RESULTS: Adolescents with a lifetime anxiety disorder had a higher
prevalence of a lifetime anger attacks (68.5%) and IED (22.9%) than adolescents
without a lifetime anxiety disorder (48.6 and 7.8%, respectively), especially
social phobia and panic disorders. Similar elevation was found for adults. Age of
onset and course of anxiety disorders did not differ by IED. Severe functional
impairment associated with anxiety was higher among adolescents (39.3%) and
adults (45.7%) with IED than those without IED (29.2 and 28.2%, respectively).
Comorbidity for all other disorders was elevated. However, individuals with
anxiety disorders and IED were no more likely to use treatment services than
those with anxiety disorders without IED. CONCLUSIONS: Individuals with IED
concomitant to anxiety disorder, especially social phobia and panic, are at
marked risk for worse functional impairment and a higher burden of comorbidity,
but onset and course of anxiety disorder do not differ, and those with anxiety
and IED are no more likely to utilize treatment services. Assessment,
identification, and specialized treatment of anger in the context of anxiety
disorders are critical to reducing burden.
PMID- 26422703
TI - High-affinity selective inhibitor against phospholipase A2 (PLA2): a
computational study.
AB - Phospholipase A2 (PLA2) is the most abundant protein found in snake venom. PLA2
induces a variety of pharmacological effects such as neurotoxicity, myotoxicity
and cardiotoxicity as well as anticoagulant, hemolytic, anti-platelet,
hypertensive, hemorrhagic and edema inducing effects. In this study, the three
dimensional structure of PLA2 of Naja sputatrix (Malayan spitting cobra) was
modeled by I-TASSER, SWISS-MODEL, PRIME and MODELLER programs. The best model was
selected based on overall stereo-chemical quality. Further, molecular dynamics
simulation was performed to know the stability of the modeled protein using
Gromacs software. Average structure was generated during the simulation period of
10 ns. High throughput virtual screening was employed through different databases
(Asinex, Hit finder, Maybridge, TOSLab and ZINC databases) against PLA2. The top
seven compounds were selected based on the docking score and free energy binding
calculations. These compounds were analyzed by quantum polarized ligand docking,
induced fit docking and density functional theory calculation. Furthermore, the
stability of lead molecules in the active site of PLA2 was employed by MD
simulation. The results show that selected lead molecules were highly stable in
the active site of PLA2.
PMID- 26422704
TI - A Morphologic and Quantitative Study of Mechanoreceptors in the Remnant Stump of
the Human Anterior Cruciate Ligament.
AB - PURPOSE: To investigate the morphology and quantity of mechanoreceptors in the
remnant stumps of injured anterior cruciate ligaments (ACLs) and the association
of the number of mechanoreceptors with the time from injury to surgery. METHODS:
Complete ACL stump specimens were collected from 40 volunteer patients who
underwent arthroscopic ACL reconstruction surgery. Serial sections, 20 MUm in
thickness, were prepared from each specimen. After H&E staining and
immunohistochemical labeling, the morphology, type, size, and quantity of the
mechanoreceptors were observed under an optical microscope. RESULTS: A total of
176 Ruffini corpuscles, 61 pacinian corpuscles, 15 Golgi-like tendon organs, and
66 atypical mechanoreceptors were observed. Free nerve endings were commonly
present in the specimens. The time from injury to surgery (log10 days) was
negatively correlated with the number of total mechanoreceptors (r = -0.43, P <
.006), Ruffini corpuscles (r = -0.45, P < .003), and the volume of the ACL stump
(r = -0.52, P < .01), and these correlations were independent of age, gender,
injury side, and career. CONCLUSIONS: The number of mechanoreceptors in an ACL
stump and the volume of the stump decreased with the time from injury to surgery.
CLINICAL RELEVANCE: This study provides a further theoretical basis for ACL
reconstruction with remnant preservation.
PMID- 26422705
TI - Comparison of Femoral Tunnel Length and Obliquity Between Transtibial,
Anteromedial Portal, and Outside-In Surgical Techniques in Single-Bundle Anterior
Cruciate Ligament Reconstruction: A Meta-analysis.
AB - PURPOSE: It is unclear whether femoral tunnel length and obliquity differ after
transtibial and independent femoral drilling techniques of anterior cruciate
ligament (ACL) reconstruction. This meta-analysis therefore compared femoral
tunnel length and obliquity in patients who underwent ACL reconstruction by the
transtibial, anteromedial (AM) portal, and outside-in (OI) techniques. METHODS:
In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and
Meta-Analyses) guidelines, all studies comparing femoral tunnel length and
obliquity with various measurement tools-from direct measurement to imaging
methods such as plain radiography, computed tomography, or magnetic resonance
imaging-in patients who underwent reconstruction by the transtibial or
independent femoral drilling (AM portal or OI) techniques were included. RESULTS:
Fourteen studies were included in the meta-analysis. The femoral tunnel length
was 7.8 to 11.0 mm longer (P < .05) and coronal obliquity was 7.5 degrees to
29.1 degrees more vertical (P < .05) with the transtibial technique than with
the AM portal or OI technique. Femoral tunnel and graft obliquity in the sagittal
plane, however, did not differ significantly (P > .05). CONCLUSIONS: ACL
reconstruction using the AM portal and OI femoral drilling techniques resulted in
a shorter length and greater coronal obliquity of the femoral tunnel than did the
transtibial technique. However, these 3 femoral drilling techniques resulted in
similar obliquities of the femoral tunnel and graft in the sagittal plane. LEVEL
OF EVIDENCE: Level III, meta-analysis.
PMID- 26422706
TI - Risk of Infection After Intra-articular Steroid Injection at the Time of Ankle
Arthroscopy in a Medicare Population.
AB - PURPOSE: To employ a national database to evaluate the association between
intraoperative corticosteroid injection at the time of ankle arthroscopy and
postoperative infection rates in Medicare patients. METHODS: A national insurance
database was queried for Medicare patients who underwent ankle arthroscopy,
including arthroscopic removal of loose body, synovectomy, and limited or
extensive debridement. Two groups were created: ankle arthroscopy with
concomitant local steroid injection (n = 459) and a control group of patients who
underwent ankle arthroscopy without intraoperative local steroid injection (n =
9,327). The demographics and Charlson Comorbidity Index of each group were
compared. Infection rates within 6 months postoperatively were assessed using
International Classification of Diseases, 9th revision, and Current Procedural
Terminology codes and compared between groups using chi(2)-tests. RESULTS: A
total of 9,786 unique patients who underwent ankle arthroscopy were included in
the study. There were no statistically significant differences between the
steroid injection study group and controls for the assessed infection-related
variables, including gender, age group, obesity, smoking, and average Charlson
Comorbidity Index. The infection rate for patients who had a local steroid
injection at the time of surgery was 3.9% (18/459 patients), compared with 1.8%
(168/9,327 patients) in the control group (odds ratio, 2.2; 95% confidence
interval, 1.4 to 3.7; P = .002.) The majority of this difference was noted
between the 65 and 79 years age groups. CONCLUSIONS: The use of intraoperative
intraarticular corticosteroid injection at the time of ankle arthroscopy in
Medicare patients is associated with significantly increased rates of
postoperative infection compared with controls without intraoperative steroid
injections.
PMID- 26422707
TI - Repair of the Posterior Third of the Meniscus During Meniscus Allograft
Transplantation: Conventional Inside-Out Repair Versus FasT-Fix All-Inside
Repair.
AB - PURPOSE: To compare conventional inside-out (IO) repair and all-inside (AI)
repair for the posterior third of the meniscus during meniscus allograft
transplantation (MAT). METHODS: Among the 64 enrolled patients, 31 patients
underwent MAT with conventional IO repair, and 33 patients underwent MAT with AI
repair using the FasT-Fix instrument for the posterior third of the meniscus
allograft. All of the patients were retrospectively evaluated through clinical
assessment at the last follow-up (54.3 months in the IO group and 55.4 months in
the AI group) and through magnetic resonance imaging assessment for meniscal
extrusion at 1 year postoperatively. Thirty patients (15 in each group) were
evaluated through second-look arthroscopy at 1 year postoperatively. RESULTS:
There was no significant difference in the mean Lysholm score (91.3 in the IO
group and 92.3 in the AI group; P = .358) or the mean Tegner activity scale (7.1
in each group; P = .885) between the 2 groups. There was no significant
difference in the mean meniscal extrusion (2.6 mm in the IO group and 2.8 mm in
the AI group; P = .454), relative percentage of extrusion value (25.6% in the IO
group and 24.7% in the AI group; P = .721), or meniscal healing on second-look
arthroscopy (P = .796) between the 2 groups. The difference in operative time
between the 2 groups was found to be statistically significant (169.9 minutes in
the IO group and 123.3 minutes in the AI group; P < .001). CONCLUSIONS: Our
comparative study on the different techniques for posterior repair of meniscus
allograft suggested that AI posterior repair using FasT-Fix could be an
alternative method to conventional IO repair as it gives a similar postoperative
result and requires a shorter operative time.
PMID- 26422708
TI - Allograft Use in Arthroscopic Labral Reconstruction of the Hip With Front-to-Back
Fixation Technique: Minimum 2-Year Follow-up.
AB - PURPOSE: To present minimum 2-year outcomes in patients who underwent a modified
technique for arthroscopic labral reconstruction using iliotibial band allograft
tissue and a front-to-back fixation. METHODS: From April 2011 to July 2012, all
consecutive arthroscopic labral reconstruction patients were included in this
Institutional Review Board-approved, prospective case series study. Inclusion
criteria were arthroscopic iliotibial band allograft labral reconstruction
performed by a single surgeon, age >=16 years at the time of arthroscopy, and a
minimum of 2 years of follow-up. Patients completed subjective questionnaires
both preoperatively and postoperatively, including Modified Harris Hip Score
(MHHS), the Lower Extremity Function Score (LEFS), Visual Analogue Scale (VAS)
pain scores, and patient satisfaction. A modified front-to-back fixation
technique for labral reconstruction was used. RESULTS: One hundred fifty-two hips
(142 patients) met the inclusion criteria for this study; 131 hips (86.2%) had
complete follow-up at a minimum of 2 years, and 21 hips (13.8%) were lost to
follow-up or had incomplete data during the study period. Seventy hips had
concomitant procedures performed; 27 microfracture, 30 chondroplasty, 26 psoas
release, 5 os acetabuli resection, and 3 Ganz osteotomy. Overall, 18 hips (13.7%)
required revision procedures at a mean of 17 months (range, 1 to 37 months) after
the labral reconstruction. In the remaining 113 hips, there was significant
improvement in all outcome measures from preoperative to most recent follow-up (P
< .0001). The mean MHHS improved by 34 points (P < .0001), and the mean LEFS
improved by 27 points (P < .0001). The mean VAS pain score improved by 3 points
at rest (P < .0001), 4 points with average pain with daily activities (P <
.0001), and 5 points with sport (P < .0001). Patients reported an overall
satisfaction of 9 (range, 1 to 10). CONCLUSIONS: Arthroscopic iliotibial band
allograft labral reconstruction of the hip shows promising outcomes at minimum 2
year follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic case series.
PMID- 26422709
TI - Medial Meniscal Root Avulsion: A Biomechanical Comparison of 4 Different Repair
Constructs.
AB - PURPOSE: To evaluate the time-zero load-to-failure strength of 4 different
constructs used to repair medial meniscal root avulsions. METHODS: Sixty fresh
frozen cadaveric knees with a mean age of 74 years were used for this study. Each
knee was dissected to isolate the attachment of the posterior root of the medial
meniscus to the tibial plateau. An Instron machine (Instron, Norwood, MA) with a
custom-designed clamp was used to avulse the intact posterior meniscal root in 12
control specimens. An additional 48 specimens were tested after transection of
the native meniscal root to evaluate the pullout strength of 4 different repair
constructs using No. 0 FiberWire suture (Arthrex, Naples, FL): a single suture (n
= 12), a double suture (n = 12), a loop stitch (n = 12), and a locking loop
stitch (n = 12). Analysis of variance was used to compare load to failure and
stiffness of all 4 groups; pair-wise, between-group differences were also
assessed. RESULTS: Repair failure occurred most commonly by suture pullout in 94%
of the specimens in the repair groups. For the controls, failure occurred most
commonly at the meniscus-clamp interface. Failure load was highest for the
control group (mean, 359.5 +/- 168 N), followed in descending order by the
locking loop stitch (191.4 +/- 45.1 N), loop stitch (119.6 +/- 55.0 N), double
suture (96.2 +/- 51.4 N), and single suture (58.2 +/- 29.6 N). The control group
was significantly stronger than 3 of the experimental groups (single suture [95%
CI, 3.8 to 11.3], double suture [95% CI, 2.1 to 6.4], and loop stitch [95% CI,
2.0 to 4.5]; P < .0001) but not the locking loop stitch (P = .003; 95% CI, 1.2 to
3.2). The locking loop stitch was significantly stronger than the single suture
(P < .0001; 95% CI, 2.0 to 5.4) and double suture (P = .003; 95% CI, 1.2 to 2.9).
The locking loop stitch was significantly stiffer than the single suture (P <
.0001; 95% CI, 3.8 to 20.3), double suture (P < .0001; 95% CI, 2.0 to 9.8), and
loop stitch (P = .03; 95% CI, 1.1 to 5.5) but not significantly different from
the control group (P = .93; 95% CI, 0.3 to 1.9). Age and gender had no effect on
pullout strength. CONCLUSIONS: The results of this study show that the locking
loop stitch provided time-zero load-to-failure strength that most closely
approximated the strength of the native meniscal root in addition to being
significantly stronger and stiffer than 3 other commonly used repair methods. The
true strength of the native meniscal root is unknown based on limitations with
our testing methodology. CLINICAL RELEVANCE: The locking loop stitch exhibited
the highest load to failure and stiffness of the 4 fixation methods tested,
despite the fact that none of the fixation methods replicated the strength of the
intact meniscal root. It is currently unknown what strength of fixation is
required for healing of meniscal root repairs.
PMID- 26422710
TI - Failures and Reoperations After Matrix-Assisted Cartilage Repair of the Knee: A
Systematic Review.
AB - PURPOSE: To quantify the reported failures and reoperations for the emerging
technique of matrix-assisted cartilage repair at short-term and midterm follow
up. METHODS: We conducted a systematic review of 3 databases from March 2004 to
February 2014 using keywords important for articular cartilage repair. Two
authors reviewed the articles, the study exclusion criteria were applied, and
articles were determined to be relevant (or not) to the research question. All
studies with a minimum of 2 years' clinical follow-up were reviewed for all
reported reoperations. The reasons for reoperations were recorded. RESULTS: We
reviewed 66 articles from the 301 articles identified in the original systematic
search. There were 60 articles on matrix-assisted cartilage transplantation and 6
articles on matrix-induced chondrogenesis. The matrix-assisted cartilage
transplantation studies reported on a total of 1,380 patients at 2 to 5 years'
follow-up. Among these, there were 72 reoperations (5%) including 46 treatment
failures (3%). These numbers increased to an 11% reoperation rate and 9%
treatment failure rate at minimum 5-year follow-up of 961 patients. The most
common procedures performed other than revision cartilage surgery or arthroplasty
were manipulation under anesthesia for arthrofibrosis (0.7%) and debridement for
graft hypertrophy (1.2%). The matrix-induced chondrogenesis studies reported on
163 patients. Among these, there were 15 reoperations (9%) that included 4
treatment failures (2%), 9 manipulations under anesthesia (6%), and 2
debridements for graft hypertrophy (1%). CONCLUSIONS: Treatment failure rates for
matrix-assisted cartilage repair increase from short-term to midterm follow-up,
with 11% of patients having undergone further surgery at a minimum of 5 years'
follow-up. These data can be used to counsel patients on the potential need for
further operative intervention after this emerging cartilage repair technique.
PMID- 26422711
TI - Panel manipulation in social stress testing: The Bath Experimental Stress Test
for Children (BEST-C).
AB - BACKGROUND: Whilst acute stress paradigms in adults make use of adult panel
members, similar paradigms modified for child participants have not manipulated
the panel. Most work has utilised an audience of adult confederates, regardless
of the age of the population being tested. The aim of this study was to trial a
social stress test for children that provided a meaningful environment using age
matched child peers as panel actors. METHODS: Thirty-three participants (7-11
years) underwent the Bath Experimental Stress Test for Children (BEST-C). Based
on the Trier Social Stress Test (TSST), it comprises a shortened six-minute
public speaking task and four-minute maths challenge. It differs from previous
stress tests by using age-matched children on the panel, pre-recorded and
presented as a live feed, and includes an expanded manipulation check of
subjective experience. Salivary cortisol was assessed at four time points, pre
post stress testing; life events, daily hassles and coping strategies were
measured through questionnaires. A simple numerical coding scheme was applied to
post-test interview data. RESULTS: The BEST-C generated a typical stress and
adaptation response in salivary cortisol (p=.032). Age and gender differences
were observed during recovery. Cortisol responses mapped directly onto three
distinct subjective response patterns: (i) expected response and recovery; (ii)
expected response, no recovery; (iii) no response. CONCLUSIONS: The BEST-C,
utilising child confederates of participant target age is a meaningful social
stress test for children. This is the first social stress test developed
specifically for children that manipulates panel characteristics by using child
confederates and a pre-recorded sham panel. Greater cortisol responses to the
test were also found to match subjective verbal accounts of the experience. It
offers a meaningful acute stress paradigm with potential applications to other
child and adolescent age groups. Furthermore, it leads the way in the use of
panel manipulation in social stress testing.
PMID- 26422712
TI - Efficacy of combined vaccination against Mycoplasma hyopneumoniae and porcine
reproductive and respiratory syndrome virus in dually infected pigs.
AB - Porcine respiratory disease complex (PRDC) is one of the main causes of economic
losses for swine producers. This complex is due to a combination of different
pathogens and their interactions. Two major pathogens involved in PRDC are
Mycoplasma hyopneumoniae (Mhp) and porcine reproductive and respiratory syndrome
virus (PRRSV). The objectives of this study were (i) to develop an experimental
model of dual Mhp/PRRSV infection in SPF pigs with European strains of Mhp and
PRRSV and (ii) to assess and compare the effects of single Mhp, single PRRSV or
combined Mhp/PRRSV vaccination against this dual infection. Pigs dually infected
with Mhp and PRRSV showed a combination of symptoms characteristic of each
pathogen but no significant exacerbation of pathogenicity. Thus, the co-infected
pigs displayed coughing and pneumonia typical of Mhp infection in addition to
PRRSV-related hyperthermia and decrease in average daily gain (ADG). Hyperthermia
was reduced in PRRSV vaccinated animals (single or combined vaccination), whereas
ADG was restored in Mhp/PRRSV vaccinated pigs only. Regarding respiratory
symptoms and lung lesions, no vaccine decreased coughing. However, all vaccines
reduced the pneumonia score but more so in animals receiving the Mhp vaccine,
whether single or combined. This vaccine also decreased the Mhp load in the
respiratory tract. In conclusion, combined vaccination against both Mhp and PRRSV
efficiently pooled the efficacy of each single PRRSV and Mhp vaccination and
could be an interesting tool to control PRDC in European swine production.
PMID- 26422713
TI - CD25 expression on residual leukemic blasts at the time of allogeneic
hematopoietic stem cell transplant predicts relapse in patients with acute
myeloid leukemia without complete remission.
AB - Recent studies have shown that CD25 expression at the time of diagnosis of acute
myeloid leukemia (AML) may be associated with an unfavorable outcome. We focus on
patients with AML without complete remission (CR) and examine the clinical
correlation between surface CD25 expression at the time of transplant and
subsequent transplant outcomes. We observed a significant difference in overall
survival (OS), disease-free survival (DFS) and cumulative incidence of relapse
(CIR) between CD25 positive (+) (n = 22) and negative (-) groups (n = 44) (2-year
OS; CD25 (+) group: 5% vs. CD25 (-) group: 40%, p < 0.0001, 2-year DFS; 5% vs.
29%, p < 0.0001, 2-year CIR; 77% vs. 52%, p = 0.03). Multivariate analysis showed
that CD25 expression was an independent adverse factor for OS (p = 0.002) and
relapse (p = 0.001). Patients with AML with residual CD25 positive blasts at the
time of transplant may require additional therapy before or after transplant to
improve survival.
PMID- 26422714
TI - [Adipocytic tumors of the salivary glands: A retrospective study].
AB - INTRODUCTION: Adipocytic tumors are the most common soft tissue mesenchymal
tumors. Their occurrence in salivary glands is rare. We studied the epidemiology,
the diagnostic and the therapeutic features of the salivary adipocytic tumors
followed in our department. PATIENTS AND METHODS: A retrospective study was
conducted in our department between January 1997 and December 2011. Nine cases of
adipocytic tumors of the salivary glands were found. Data were collected from
medical records and processed by Excel. RESULTS: Mean age was 44 with a clear
predominance of males (sex ratio: 3.5). In 8 cases the tumors were benign (7
lipomas and 1 lipofibroma). The only malignant tumor was a metastatic myxoid
liposarcoma. Parotid was the main location (8 cases/9). Ultrasonography and MRI
were prescribed. The treatment was tumor and parotid gland removal with
conservation of the facial nerve excepted in the malignant case. One transient
facial palsy, two earlobe dysesthesia and one retromandibular depression were
observed. No recurrence was noted. DISCUSSION: Our study confirmed the
epidemiological profile of these adipocytic salivary gland tumors, which are
rarely observed, but mainly in the parotid gland. They are often benign and
lipoma is the main histological type.
PMID- 26422715
TI - Characteristics of Consecutive Esophageal Motility Diagnoses After a Decade of
Change.
AB - BACKGROUND AND AIMS: Combined multichannel intraluminal impedance and esophageal
manometry (MII-EM) measures concomitantly bolus transit and pressure changes
allowing determination of the functional impact of esophageal motility
abnormalities. Ten years ago our laboratory reported MII-EM results in 350
consecutive patients. Since then high-resolution impedance manometry (HRIM)
became available and the definitions of ineffective esophageal motility (IEM) and
nutcracker esophagus were revised. The aim of this study was to assess the impact
of these developments on esophageal function testing. METHODS: From August 2012
through May 2013, HRIM was performed in 350 patients referred for esophageal
function testing. Each patient received 10 liquid and 10 viscous swallows. While
taking advantage of the new technology and revised criteria, HRIM findings were
classified according to the conventional criteria to allow more appropriate
comparison with our earlier analysis. RESULTS: Compared with the study performed
10 years ago, the prevalence of normal manometry (36% vs. 35%), achalasia (7% vs.
8%), scleroderma (1% vs. 1%), hypertensive lower esophageal sphincter (LES) (7%
vs. 7%), and hypotensive LES (1% vs. 2%) remained the same, whereas the
prevalence of distal esophageal spasm (9% vs. 3%), nutcracker esophagus (9% vs.
3%), and poorly relaxing LES (10% vs. 3%) decreased and the prevalence of IEM
increased (20% vs. 31%) significantly. Compared with the early study, normal
liquid bolus transit was significantly different in patients with hypertensive
LES (96% vs. 57%) and poorly relaxing LES (55% vs. 100%). CONCLUSIONS: This study
brings to light the increase in prevalence of IEM. In addition, it suggests that
the hypertensive LES and poorly relaxing LES may each affect bolus transit in
about half of these patients.
PMID- 26422716
TI - Zinc Triflate Catalyzed C-Benzylation: Chemo- and Regioselective Route to Amido
Substituted Diaryl and Arylheteroarylmethanes.
AB - An unprecedented zinc triflate catalyzed selective C-benzylation of anilides and
heteroaryl amides with benzyl chlorides having electron-donating group at para
position is reported. The protocol offers moderate to high yield of para-amido
substituted diaryl and arylheteroarylmethanes, uses cheap and easily available
benzyl chlorides as the benzylating agent, catalytic amount of zinc triflate, and
takes place under ambient conditions. Aminodiarylmethane derivatives can be
obtained by hydrolysis of the corresponding amides. The methodology has also been
applied for preparing dimethoxydiarylmethanes in good yields, which are the key
precursors for synthesis of phenolic natural products.
PMID- 26422717
TI - Allergic Contact Dermatitis Due to Dittrichia viscosa.
PMID- 26422718
TI - Risk Analysis of Pneumonitis in Taxane Therapy After Chemoradiotherapy for
Patients With Metastatic or Recurrent Esophageal Cancer.
AB - OBJECTIVES: Taxane chemotherapy for esophageal cancer causes pneumonitis, not
only by itself but also by radiation recall. This study aimed to clarify the risk
of pneumonitis in patients with esophageal cancer who receive taxane therapy
after chemoradiotherapy. METHODS: The data of 129 patients with metastatic or
recurrent esophageal cancer who initiated taxane therapy between September 2002
and June 2013 were retrospectively analyzed. Patient selection criteria were as
follows: performance status <=2, preserved organ functions, previous
chemoradiotherapy with a radiation dose of >=50 Gy, grade 0 or 1 pneumonitis at
taxane initiation, and no concomitant malignancy. Logistic regression analysis
was performed to identify risk factors for pneumonitis. RESULTS: Patient
characteristics were as follows: males/females, 116/13; median age, 63 years
(range, 44 to 80 y); performance status of 0/1/2, 61/60/8; smoking history, 112
(88%); location of the primary tumor Ce/Ut/Mt/Lt/Ae 12/30/66/20/1; median
radiation dose, 60 Gy; history of radiation pneumonitis, 39 (30%); history of
other pulmonary disease, 4 (3%); and median duration between the last radiation
therapy (RT) exposure and taxane initiation, 6.1 months (range, 1.0 to 71 mo).
During the median observation period of 7.8 months from taxane initiation, the
incidence of grade 2 and 3 pneumonitis was observed in 7 (5.4%) and 3 (2.3%)
patients, respectively. No patient died of pneumonitis. The only independent risk
factor for pneumonitis was a <=4-month period between the last RT exposure and
taxane initiation (P=0.03). CONCLUSIONS: A short period between the last RT
exposure and taxane initiation is an independent risk factor for pneumonitis
development.
PMID- 26422719
TI - Transforming Turkey's Health System--Lessons for Universal Coverage.
PMID- 26422720
TI - Reduced-Nicotine Cigarettes--A Promising Regulatory Pathway.
PMID- 26422721
TI - Cardiometabolic Risks and Severity of Obesity in Children and Young Adults.
AB - BACKGROUND: The prevalence of severe obesity among children and young adults has
increased over the past decade. Although the prevalence of cardiometabolic risk
factors is relatively low among children and young adults who are overweight or
obese, those with more severe forms of obesity may be at greater risk. METHODS:
We performed a cross-sectional analysis of data from overweight or obese children
and young adults 3 to 19 years of age who were included in the National Health
and Nutrition Examination Survey from 1999 through 2012 to assess the prevalence
of multiple cardiometabolic risk factors according to the severity of obesity.
Weight status was classified on the basis of measured height and weight. We used
standard definitions of abnormal values for total cholesterol, high-density
lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol,
triglycerides, blood pressure, glycated hemoglobin, and fasting glucose and
report the prevalence of abnormal values in children and young adults according
to weight status. RESULTS: Among 8579 children and young adults with a body-mass
index at the 85th percentile or higher (according to the Centers for Disease
Control and Prevention growth charts), 46.9% were overweight, 36.4% had class I
obesity, 11.9% had class II obesity, and 4.8% had class III obesity. Mean values
for some, but not all, cardiometabolic variables were higher with greater
severity of obesity in both male and female participants, and the values were
higher in male participants than in female participants; for HDL cholesterol, the
mean values were lower with greater severity of obesity. Multivariable models
that controlled for age, race or ethnic group, and sex showed that the greater
the severity of obesity, the higher the risks of a low HDL cholesterol level,
high systolic and diastolic blood pressures, and high triglyceride and glycated
hemoglobin levels. CONCLUSIONS: Severe obesity in children and young adults was
associated with an increased prevalence of cardiometabolic risk factors,
particularly among boys and young men.
PMID- 26422722
TI - Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis.
AB - BACKGROUND: Early clinical studies suggested that the anti-interleukin-17
receptor A monoclonal antibody brodalumab has efficacy in the treatment of
psoriasis. METHODS: In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients
with moderate-to-severe psoriasis were randomly assigned to receive brodalumab
(210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body
weight <=100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients
receiving brodalumab were randomly assigned again to receive a brodalumab
maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks,
or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab
every 12 weeks, and patients receiving placebo received 210 mg of brodalumab
every 2 weeks. The primary aims were to evaluate the superiority of brodalumab
over placebo at week 12 with respect to at least a 75% reduction in the psoriasis
area-and-severity index score (PASI 75) and a static physician's global
assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the
superiority of brodalumab over ustekinumab at week 12 with respect to a 100%
reduction in PASI score (PASI 100). RESULTS: At week 12, the PASI 75 response
rates were higher with brodalumab at the 210-mg and 140-mg doses than with
placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%,
respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1
were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates
were significantly higher with 210 mg of brodalumab than with ustekinumab (44%
vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response
rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison
with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were
higher with brodalumab and with ustekinumab than with placebo. Mild or moderate
candida infections were more frequent with brodalumab than with ustekinumab or
placebo. Through week 52, the rates of serious infectious episodes were 1.0
(AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab.
CONCLUSIONS: Brodalumab treatment resulted in significant clinical improvements
in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and
AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).
PMID- 26422725
TI - Maintenance Intravenous Fluids in Acutely Ill Patients.
PMID- 26422726
TI - IMAGES IN CLINICAL MEDICINE. Pseudoaneurysm after Transradial Coronary
Angiography.
PMID- 26422723
TI - Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis.
AB - BACKGROUND: In a phase 2 study, the inhibition of the interleukin-17A receptor
improved signs and symptoms of psoriatic arthritis. We sought to evaluate the
efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody,
in such patients. METHODS: In this double-blind, phase 3 study, 606 patients with
psoriatic arthritis were randomly assigned in a 1:1:1 ratio to receive
intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4,
followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4
weeks, or placebo. Patients in the placebo group were switched to subcutaneous
secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical
response. The primary end point was the proportion of patients with an American
College of Rheumatology 20 (ACR20) response at week 24, defined as a 20%
improvement from baseline in the number of tender and swollen joints and at least
three other important domains. RESULTS: ACR20 response rates at week 24 were
significantly higher in the group receiving secukinumab at doses of 150 mg
(50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for
both comparisons with placebo). Secondary end points, including the ACR50
response and joint structural damage, were significantly better in the
secukinumab groups than in the placebo group. Improvements were sustained through
52 weeks. Infections, including candida, were more common in the secukinumab
groups. Throughout the study (mean secukinumab exposure, 438.5 days; mean placebo
exposure, 128.5 days), four patients in the secukinumab groups had a stroke (0.6
per 100 patient-years; 95% confidence interval [CI], 0.2 to 1.5), and two had a
myocardial infarction (0.3 per 100 patient-years; 95% CI, 0.0 to 1.0), as
compared with no patients in the placebo group. CONCLUSIONS: Secukinumab was more
effective than placebo in patients with psoriatic arthritis, which validates
interleukin-17A as a therapeutic target. Infections were more common in the
secukinumab groups than in the placebo group. The study was neither large enough
nor long enough to evaluate uncommon serious adverse events or the risks
associated with long-term use. (Funded by Novartis Pharma; ClinicalTrials.gov
number, NCT01392326.).
PMID- 26422724
TI - Randomized Trial of Reduced-Nicotine Standards for Cigarettes.
AB - BACKGROUND: The Food and Drug Administration can set standards that reduce the
nicotine content of cigarettes. METHODS: We conducted a double-blind, parallel,
randomized clinical trial between June 2013 and July 2014 at 10 sites.
Eligibility criteria included an age of 18 years or older, smoking of five or
more cigarettes per day, and no current interest in quitting smoking.
Participants were randomly assigned to smoke for 6 weeks either their usual brand
of cigarettes or one of six types of investigational cigarettes, provided free.
The investigational cigarettes had nicotine content ranging from 15.8 mg per gram
of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome
was the number of cigarettes smoked per day during week 6. RESULTS: A total of
840 participants underwent randomization, and 780 completed the 6-week study.
During week 6, the average number of cigarettes smoked per day was lower for
participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of
nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than
for participants randomly assigned to their usual brand or to cigarettes
containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001).
Participants assigned to cigarettes with 5.2 mg per gram smoked an average of
20.8 cigarettes per day, which did not differ significantly from the average
number among those who smoked control cigarettes. Cigarettes with lower nicotine
content, as compared with control cigarettes, reduced exposure to and dependence
on nicotine, as well as craving during abstinence from smoking, without
significantly increasing the expired carbon monoxide level or total puff volume,
suggesting minimal compensation. Adverse events were generally mild and similar
among groups. CONCLUSIONS: In this 6-week study, reduced-nicotine cigarettes
versus standard-nicotine cigarettes reduced nicotine exposure and dependence and
the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse
and the Food and Drug Administration Center for Tobacco Products;
ClinicalTrials.gov number, NCT01681875.).
PMID- 26422727
TI - CLINICAL PROBLEM-SOLVING. Springing a Leak.
PMID- 26422728
TI - Hardly Tendentious--Repairing Like with Like.
PMID- 26422730
TI - High-Flow Nasal Cannula Oxygen in Respiratory Failure.
PMID- 26422729
TI - High-Flow Nasal Cannula Oxygen in Respiratory Failure.
PMID- 26422731
TI - High-Flow Nasal Cannula Oxygen in Respiratory Failure.
PMID- 26422732
TI - High-Flow Nasal Cannula Oxygen in Respiratory Failure.
PMID- 26422733
TI - High-Flow Nasal Cannula Oxygen in Respiratory Failure.
PMID- 26422734
TI - Efficacy of a Sexual Assault Resistance Program for University Women.
PMID- 26422735
TI - Efficacy of a Sexual Assault Resistance Program for University Women.
PMID- 26422736
TI - ClinGen and Genetic Testing.
PMID- 26422737
TI - ClinGen and Genetic Testing.
PMID- 26422738
TI - ClinGen and Genetic Testing.
PMID- 26422739
TI - ClinGen and Genetic Testing.
PMID- 26422740
TI - ClinGen and Genetic Testing.
PMID- 26422741
TI - HIV Outbreak in Indiana.
PMID- 26422742
TI - HIV Outbreak in Indiana.
PMID- 26422744
TI - IMAGES IN CLINICAL MEDICINE. An Acute Dystonic Reaction after Treatment with
Metoclopramide.
PMID- 26422743
TI - Ibrutinib in Refractory Classic Hodgkin's Lymphoma.
PMID- 26422745
TI - Influence of Quality of Relationship Between Patient With Melanoma and Partner on
Partner-Assisted Skin Examination Education: A Randomized Clinical Trial.
AB - IMPORTANCE: Melanoma has a high survival rate if it is detected early. Training
patients with early-stage melanoma who are at risk of developing new melanomas to
perform skin self-examination (SSE) may improve survival. OBJECTIVE: To examine
for whom the intervention works best in a sample composed of dyads of patients
with melanoma and skin-check partners who received an SSE intervention vs
customary care. DESIGN, SETTING, AND PARTICIPANTS: For 494 patients with stage 0
to IIB melanoma (mean age, 55 years; 253 [51.2%] females) and their skin-check
partners (mean age, 55 years; 280 [56.7%] females), a randomized clinical trial
was conducted in ambulatory care dermatologic offices from June 6, 2011, to April
14, 2014. Follow-up assessments were performed at 12 months. Analysis was
performed between March 23 and June 25, 2015. METHODS: Dyads of 494 patients and
their partners were randomly assigned to receive the intervention (395 patients)
or customary care (control) (99 patients). The main outcome was patient SSE self
efficacy. Partner motivation to assist with SSE and relationship quality (eg,
agreeability, activities with partner, and happiness) were assessed for
moderation of the influence of the intervention's effect on SSE self-efficacy.
RESULTS: Relationship quality, defined by activities with the partner (beta =
0.892, SE = 0.432, t = -2.066; P = .001) and happiness (beta = -4.586, SE =
2.044, t = -2.24; P = .001), significantly moderated the intervention effects on
patients' SSE self-efficacy. In contrast, patient-partner agreeability (beta =
0.262, SE = 0.148, t = -1.773; P = .09) and partner motivation (beta = -0.328, SE
= 1.024, t = -0.320; P = .10) did not significantly moderate the intervention
effects on patients' SSE self-efficacy. Differences between the conditions were
highest when activities performed with the partner were below average (mean
difference, 6.652; P = .001) and when happiness was below average (mean
difference, 7.000; P = .001). Although everyone receiving the intervention
experienced some benefit, the findings indicate the greatest increases in self
efficacy were observed for those with below-average activities performed with the
partner and happiness. CONCLUSIONS AND RELEVANCE: The training of patients with
melanoma and their partners in early-detection SSE benefited some more than
others. Pairs who have low relationship quality, as determined by activities
performed with the partner and happiness, may have received the greatest benefits
from the training intervention because they were given an activity to perform
together. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01432860.
PMID- 26422747
TI - Firearm Injury in the United States: An Overview of an Evolving Public Health
Problem.
PMID- 26422746
TI - Frailty for Surgeons: Review of a National Institute on Aging Conference on
Frailty for Specialists.
PMID- 26422748
TI - Coupling Underwater Superoleophobic Membranes with Magnetic Pickering Emulsions
for Fouling-Free Separation of Crude Oil/Water Mixtures: An Experimental and
Theoretical Study.
AB - Oil/water separations have become an area of great interest, as growing oil
extraction activities are increasing the generation of oily wastewaters as well
as increasing the risk of oil spills. Here, we demonstrate a membrane-based and
fouling-free oil/water separation method that couples carbon nanotube-poly(vinyl
alcohol) underwater superoleophobic ultrafiltration membranes with magnetic
Pickering emulsions. We demonstrate that this process is insensitive to low water
temperatures, high ionic strength, or crude oil loading, while allowing operation
at high permeate fluxes and producing high quality permeate. Furthermore, we
develop a theoretical framework that analyzes the stability of Pickering
emulsions under filtration mechanics, relating membrane surface properties and
hydrodynamic conditions in the Pickering emulsion cake layer to membrane
performance. Finally, we demonstrate the recovery and recyclability of the
nanomagnetite used to form the Pickering emulsions through a magnetic separation
step, resulting in an environmentally friendly, continuous process for oil/water
separation.
PMID- 26422749
TI - A combined binding mechanism of nonionic ethoxylated surfactants to bovine serum
albumin revealed by fluorescence and circular dichroism.
AB - The study systematically investigates aqueous mixtures of fixed bovine serum
albumin (BSA) and various ethoxylated nonionic surfactants belonging to a
homologous series or not. Mono-disperse tetra-(C12E4), hexa-(C12E6) and octa
ethyleneglycol mono-n-dodecyl ether (C12E8), and poly-disperse eicosa
ethyleneglycol mono-n-tetradecyl ether (C14EO20) are respectively employed.
Fluorescence and circular dichroism measurements are performed at
surfactant/protein molar ratios (rm)s lower and higher than one. We aim to get
new insights into the binding mechanism of these species and to differentiate
among the interaction abilities of these surfactants. The relative magnitude of
the binding thermodynamic parameters by fluorescence, and the increase of alpha
helix prove that hydrogen bonding drives the interaction next to the hydrophobic
attraction. C12En (n=4,6,8) develop more H bonds with the albumin than C14EO20
owing to a zigzag conformation of their short ethyleneoxide chains. Among the
homologous surfactants, C12E6 has a slightly stronger interaction with BSA due to
a maximal number of H bonds at a minimal hindering. Static fluorescence and
dynamic fluorescence indicate an inter-conversion between the tryptophan (Trp)
rotamers which happens around the surfactants critical micellar concentration.
For C14EO20, the meander conformation of the polar group determines a less
evident conversion of the Trp rotamers and smaller alpha-helix rise. Binding
isotherms of the homologous surfactants and the fluorescence quenching mechanism
by C12E6 are also provided.
PMID- 26422750
TI - Remarkable Role of C-I...N Halogen Bonding in Thixotropic 'Halo'gel Formation.
AB - Halogen-bonding-induced self-assembly in the solution of equimolar mixtures of
certain pyridyl-ended oligo p-phenylenevinylene (OPV)-derivatives with 1,4
diiodotetrafluorobenzene is reported. The mode of self-assembly, that is,
cocrystallization, thixotropic gelation, or precipitation, depends strongly on
the nature of chains (n-alkyl chains as a function of length or short oxyethylene
chain) appended to the OPV-backbone as well as on the cooling rate of the
corresponding hot solution. Single-crystal X-ray diffraction studies of the
cocrystals reveal the "infinite" chain formation via C-I...N halogen-bonding
interactions between the two components. In addition, multiple noncovalent
interactions induce cross-links among these halogen-bonded "infinite" chains.
Interestingly, the molecular packing in the "Cogel" bearing OPV-derivative with
oxyethylene chains is found to be very similar to that of the cocrystal of the
same.
PMID- 26422751
TI - Phoniatry: otorhinolaryngology expands its limits.
PMID- 26422752
TI - Effects of Tris(1,3-dichloro-2-propyl) Phosphate on Growth, Reproduction, and
Gene Transcription of Daphnia magna at Environmentally Relevant Concentrations.
AB - The synthetic flame retardant tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has
been frequently detected in natural waters, and its maximum concentration ever
reported is 377 ng/L. However, information on the adverse effects of
environmentally relevant concentrations of TDCIPP on aquatic organisms are
totally unknown. In this study, <12-h old water fleas, D. magna, were exposed to
concentrations of 0, 65+/-7.1, 550+/-33, or 6500+/-1400 ng/L TDCIPP, and dose-
and time-dependent effects on reproduction and development were evaluated.
Sequences of genes of D. magna were obtained from the National Center for
Biotechnology Information and were used to develop PCR arrays for D. magna.
Arrays were then used to study transcriptional responses of D. magna to TDCIPP.
Exposure to environmentally relevant concentrations of TDCIPP significantly
decreased fecundity as well as length of F0 and F1 generations. Transcriptional
responses showed that, of the 155 genes tested, expressions of 57 genes were
significantly changed, and some changes occurred following exposure to
environmentally relevant concentrations (i.e., 65+/-7.1 and 550+/-23 ng/L).
Furthermore, pathways related to protein synthesis and metabolism and endocytosis
were considered to be significantly affected in a dose- and time-dependent manner
and might be responsible for TDCIPP-induced reproductive and developmental
toxicities.
PMID- 26422755
TI - Alice in Wonderland Syndrome, Burning Mouth Syndrome, Cold Stimulus Headache, and
HaNDL: Narrative Review.
AB - BACKGROUND: Unusual headache syndromes are not as infrequent in clinical practice
as was generally believed. About three fourths of the classified headache
disorders found in the ICHD-II can be considered rare. OBJECTIVE: The aim of this
narrative review was to perform a literature review of the pathophysiology,
clinical presentation, diagnostic criteria, and treatment of the following
unusual headache disorders: Alice in Wonderland syndrome, burning mouth syndrome,
cold stimulus headache, and the syndrome of transient headache and neurologic
deficits with cerebrospinal fluid lymphocytosis. METHOD: A literature review was
performed using PubMed for each of the abovementioned headache disorders.
CONCLUSION: The unusual headache syndromes as a distinct group of disorders are
not as infrequent in clinical practice as was generally believed. Some of them,
albeit considered as unusual, may occur with relative frequency, such as cold
stimulus headache and burning mouth syndrome.
PMID- 26422753
TI - CD11b immunophenotyping identifies inflammatory profiles in the mouse and human
lungs.
AB - The development of easily accessible tools for human immunophenotyping to
classify patients into discrete disease endotypes is advancing personalized
therapy. However, no systematic approach has been developed for the study of
inflammatory lung diseases with often complex and highly heterogeneous disease
etiologies. We have devised an internally standardized flow cytometry approach
that can identify parallel inflammatory alveolar macrophage phenotypes in both
the mouse and human lungs. In mice, lung innate immune cell alterations during
endotoxin challenge, influenza virus infection, and in two genetic models of
chronic obstructive lung disease could be segregated based on the presence or
absence of CD11b alveolar macrophage upregulation and lung eosinophilia.
Additionally, heightened alveolar macrophage CD11b expression was a novel feature
of acute lung exacerbations in the SHIP-1(-/-) model of chronic obstructive lung
disease, and anti-CD11b antibody administration selectively blocked inflammatory
CD11b(pos) but not homeostatic CD11b(neg) alveolar macrophages in vivo. The
identification of analogous profiles in respiratory disease patients highlights
this approach as a translational avenue for lung disease endotyping and suggests
that heterogeneous innate immune cell phenotypes are an underappreciated
component of the human lung disease microenvironment.
PMID- 26422754
TI - Social stress-enhanced severity of Citrobacter rodentium-induced colitis is CCL2
dependent and attenuated by probiotic Lactobacillus reuteri.
AB - Psychological stressors are known to affect colonic diseases but the mechanisms
by which this occurs, and whether probiotics can prevent stressor effects, are
not understood. Because inflammatory monocytes that traffic into the colon can
exacerbate colitis, we tested whether CCL2, a chemokine involved in monocyte
recruitment, was necessary for stressor-induced exacerbation of infectious
colitis. Mice were exposed to a social disruption stressor that entails repeated
social defeat. During stressor exposure, mice were orally challenged with
Citrobacter rodentium to induce a colonic inflammatory response. Exposure to the
stressor during challenge resulted in significantly higher colonic pathogen
levels, translocation to the spleen, increases in colonic macrophages, and
increases in inflammatory cytokines and chemokines. The stressor-enhanced
severity of C. rodentium-induced colitis was not evident in CCL2(-/-) mice,
indicating the effects of the stressor are CCL2-dependent. In addition, we tested
whether probiotic intervention could attenuate stressor-enhanced infectious
colitis by reducing monocyte/macrophage accumulation. Treating mice with
probiotic Lactobacillus reuteri reduced CCL2 mRNA levels in the colon and
attenuated stressor-enhanced infectious colitis. These data demonstrate that
probiotic L. reuteri can prevent the exacerbating effects of stressor exposure on
pathogen-induced colitis, and suggest that one mechanism by which this occurs is
through downregulation of the chemokine CCL2.
PMID- 26422757
TI - Neuron-like differentiation of mesenchymal stem cells on silicon nanowires.
AB - The behavior of mammalian cells on vertical nanowire (NW) arrays, including cell
spreading and the dynamic distribution of focal adhesions and cytoskeletal
proteins, has been intensively studied to extend the implications for cellular
manipulations in vitro. Prompted by the result that cells on silicon (Si) NWs
showed morphological changes and reduced migration rates, we have explored the
transition of mesenchymal stem cells into a neuronal lineage by using SiNWs with
varying lengths. When human mesenchymal stem cells (hMSCs) were cultured on the
longest SiNWs for 3 days, most of the cells exhibited elongated shapes with
neurite-like extensions and dot-like focal adhesions that were prominently
observed along with actin filaments. Under these circumstances, the cell motility
analyzed by live cell imaging was found to decrease due to the presence of SiNWs.
In addition, the slowed growth rate, as well as the reduced population of S phase
cells, suggested that the cell cycle was likely arrested in response to the
differentiation process. Furthermore, we measured the mRNA levels of several
lineage-specific markers to confirm that the SiNWs actually induced neuron-like
differentiation of the hMSCs while hampering their osteogenic differentiation.
Taken together, our results implied that SiNWs were capable of inducing active
reorganization of cellular behaviors, collectively guiding the fate of hMSCs into
the neural lineage even in the absence of any inducing reagent.
PMID- 26422756
TI - SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells.
AB - AIM: Oxidative stress is a key contributor to endothelial dysfunction and
associated cardiovascular pathogenesis. Hydrogen sulfide (H2S) is an antioxidant
gasotransmitter that protects endothelial cells against oxidative stress.
Sirtuin3 (SIRT3), which belongs to the silent information regulator 2 (SIR2)
family, is an important deacetylase under oxidative stress. H2S is able to
regulate the activity of several sirtuins. The present study aims to investigate
the role of SIRT3 in the antioxidant effect of H2S in endothelial cells. RESULTS:
Cultured EA.hy926 endothelial cells were exposed to hydrogen peroxide (H2O2) as a
model of oxidative stress-induced cell injury. GYY4137, a slow-releasing H2S
donor, improved cell viability, reduced oxidative stress and apoptosis, and
improved mitochondrial function following H2O2 treatment. H2S reversed the
stimulation of MAPK phosphorylation, downregulation of SIRT3 mRNA and reduction
of the superoxide dismutase 2 and isocitrate dehydrogenase 2 expression which
were induced by H2O2. H2S also increased activator protein 1 (AP-1) binding
activity with SIRT3 promoter and this effect was absent in the presence of the
specific AP-1 inhibitor, SR11302 or curcumin. Paraquat administration to mice
induced a defected endothelium-dependent aortic vasodilatation and increased
oxidative stress in both mouse aorta and small mesenteric artery, which were
alleviated by GYY4137 treatment. This vasoprotective effect of H2S was absent in
SIRT3 knockout mice. INNOVATION: The present results highlight a novel role for
SIRT3 in the protective effect of H2S against oxidant damage in the endothelium
both in vitro and in vivo. CONCLUSION: H2S enhances AP-1 binding activity with
the SIRT3 promoter, thereby upregulating SIRT3 expression and ultimately reducing
oxidant-provoked vascular endothelial dysfunction. Antioxid. Redox Signal. 24,
329-343.
PMID- 26422758
TI - Biophysical Characterization of the Type III Secretion System Translocator
Proteins and the Translocator Proteins Attached to Bacterium-Like Particles.
AB - Diarrhea caused by Shigella, Salmonella, and Yersinia is an important public
health problem, but development of safe and effective vaccines against such
diseases is challenging. A new antigen delivery platform called bacterium-like
particles (BLPs) was explored as a means for delivering protective antigens from
the type III secretion systems (T3SS) of these pathogens. BLPs are peptidoglycan
skeletons derived from Lactococcus lactis that are safe for newborns and can
carry multiple antigens. Hydrophobic T3SS translocator proteins were fused to a
peptidoglycan anchor (PA) for BLP attachment. The proteins and protein-BLP
complexes associated with BLPs were characterized and the resulting data used to
create three-index empirical phase diagrams (EPDs). On the basis of these EPDs,
IpaB (Shigella) and SipB (Salmonella) behave distinctly from YopB (Yersinia)
under different environmental stresses. Adding the PA domain appears to enhance
the stability of both the PA and translocator proteins, which was confirmed using
differential scanning calorimetry, and although the particles dominated the
spectroscopic signals in the protein-loaded BLPs, structural changes in the
proteins were still detected. The protein-BLPs were most stable near neutral pH,
but these proteins' hydrophobicity made them sensitive to environmental stresses.
PMID- 26422759
TI - Music as a mediator between ethnicity and substance use among college students.
AB - The current study examined the relationship between substance use references
contained in music lyrics and videos and the attitudes and behaviors regarding
substance use of White non-Hispanic, African American, and Hispanic emerging
adults from a cultivation and social norms framework by assessing 425 male and
female college students. It was hypothesized that there would be ethnic
variations in perceived harm from substance use and reported recent substance use
and that exposure to substance use references contained in music could mediate
this relationship. Results confirmed ethnic differences in perceived risk
associated with substance use as well as reported substance use with White non
Hispanic college students reporting the least perceived risk and the most
substance use. African American college students reported the most perceived risk
associated with substance use and the least amount of reported substance use.
Results of the Test of Joint Significance confirmed the mediational model in that
participant ethnicity was associated with exposure to substance use references in
music lyrics and music videos. Substance use references in music lyrics, then,
was able to predict actual reported substance use of participants but not
perceived risk associated with substance use.
PMID- 26422760
TI - Controlled Lateral Positioning of Microparticles Inside Droplets Using
Acoustophoresis.
AB - In this paper, we utilize bulk acoustic waves to control the position of
microparticles inside droplets in two-phase microfluidic systems and demonstrate
a method to enrich the microparticles. In droplet microfluidics, different unit
operations are combined and integrated on-chip to miniaturize complex biochemical
assays. We present a droplet unit operation capable of controlling the position
of microparticles during a trident shaped droplet split. An acoustic standing
wave field is generated in the microchannel, and the acoustic forces direct the
encapsulated microparticles to the center of the droplets. The method is generic,
requires no labeling of the microparticles, and is operated in a noncontact
fashion. It was possible to achieve 2+-fold enrichment of polystyrene beads (5
MUm in diameter) in the center daughter droplet with an average recovery of 89%
of the beads. Red blood cells were also successfully manipulated inside droplets.
These results show the possibility to use acoustophoresis in two-phase systems to
enrich microparticles and open up the possibility for new droplet-based assays
that are not performed today.
PMID- 26422761
TI - The Morphology of TiO2 (B) Nanoparticles.
AB - The morphology of a nanomaterial (geometric shape and dimension) has a
significant impact on its physical and chemical properties. It is, therefore,
essential to determine the morphology of nanomaterials so as to link shape with
performance in specific applications. In practice, structural features with
different length scales are encoded in a specific angular range of the X-ray or
neutron total scattering pattern of the material. By combining small- and wide
angle scattering (typically X-ray) experiments, the full angular range can be
covered, allowing structure to be determined accurately at both the meso- and the
nanoscale. In this Article, a comprehensive morphology analysis of lithium-ion
battery anode material, TiO2 (B) nanoparticles (described in Ren, Y.; Liu, Z.;
Pourpoint, F.; Armstrong, A. R.; Grey, C. P.; Bruce, P. G. Angew. Chem. Int. Ed.
2012, 51, 2164), incorporating structure modeling with small-angle X-ray
scattering (SAXS), pair distribution function (PDF), and X-ray powder diffraction
(XRPD) techniques, is presented. The particles are oblate-shaped, contracted
along the [010] direction, this particular morphology providing a plausible
rationale for the excellent electrochemical behavior of these TiO2(B)
nanoparticles, while also provides a structural foundation to model the strain
driven distortion induced by lithiation. The work demonstrates the importance of
analyzing various structure features at multiple length scales to determine the
morphologies of nanomaterials.
PMID- 26422762
TI - Discussion.
PMID- 26422763
TI - Discussion.
PMID- 26422764
TI - Early outcome of thoracoscopic and hybrid esophagectomy: Propensity-matched
comparative analysis.
AB - BACKGROUND: Transthoracic esophagectomy remains the current therapeutic standard
for localized esophageal carcinoma. Minimally invasive surgery has proven at
least equivalent to open surgery regarding the early outcomes, but only 1
randomized study has compared the thoracoscopic with the thoracotomy approach.
The primary objective of this study was to assess the early outcome of the
thoracoscopic prone esophagectomy (TPE) and the hybrid Ivor Lewis (HIL)
esophagectomy in 2 concurrent patient cohorts. METHODS: We compared the 1-year
outcome of 3-stage TPE and 2-stage HIL done over the same time period in a single
center. The propensity score matching method was used to reduce selection bias by
creating 2 groups of patients similarly likely to receive a treatment on the
basis of measured baseline characteristics. After generating propensity scores
using the covariates of age, sex, body mass index, forced expiration volume at 1
second, Charlson comorbidity index, American Society of Anesthesiologists score,
histologic tumor type, tumor site, pTNM stage, and neoadjuvant therapy, 93 TPE
patients were matched with 197 HIL patients using a 1:1 ratio and the nearest
neighbor score matching. Main outcome measure was the incidence of postoperative
complications. RESULTS: Operative time was longer in TPE patients (P < .01). All
postoperative outcomes, including morbidity, mortality, nodal harvest, R0
resection rate, and 1-year survival rates were similar in the 2 matched groups.
CONCLUSION: Both operative approaches are safe and effective; using 1 or the
other depends on the tumor site, surgeon experience and preference, and patient
expectations.
PMID- 26422765
TI - A novel lateral-approach laryngeal ultrasonography for vocal cord evaluation.
AB - BACKGROUND: Laryngeal ultrasonography (LUS) is a new method of vocal cord (VC)
evaluation in patients with risk of vocal cord palsy (VCP). The previously
described anterior-approach LUS reportedly, however, has high failure rate of VC
visualization in male patients. We devised a novel lateral-approach LUS to
overcome this limitation. METHODS: A total of 382 (82 male, 300 female)
consecutive LUS and direct laryngoscopy (DL) examinations were performed on
perioperative thyroidectomy and parathyroidectomy patients. The anterior-approach
LUS was used for female patients whereas the lateral-approach LUS was used for
male patients. Findings were cross-validated independently with DL examinations.
RESULTS: Both anterior and lateral LUS methods had 100% visualization rate (no
failed visualization) with an overall sensitivity of 100% (23/23) and specificity
of 99.2% (356/359) for VCP. Among the 300 female patients, 18 patients had VCP.
Sensitivity and specificity of anterior-approach LUS were 100% (18/18) and 99.3%
(280/282), respectively. Among the 80 male patients, 5 patients had VCP.
Sensitivity and specificity of lateral-approach LU were 100% (5/5) and 98.7%
(76/77), respectively. CONCLUSION: The new LUS approach significantly enhances
the visualization of vocal cords and, therefore, overall diagnostic efficacy of
LUS in male patients.
PMID- 26422766
TI - Cosyntropin stimulation testing on postoperative day 1 allows for selective
glucocorticoid replacement therapy after adrenalectomy for hypercortisolism:
Results of a novel, multidisciplinary institutional protocol.
AB - BACKGROUND: Secondary adrenal insufficiency (AI) can occur after unilateral
adrenalectomy for adrenal-dependent hypercortisolism. Postoperative
glucocorticoid replacement (GR), although given routinely, may not be necessary.
We sought to identify factors that, in combination with postoperative day 1
cosyntropin stimulation testing (POD1-CST), would predict the need for GR.
METHODS: We reviewed 31 consecutive patients who underwent unilateral
adrenalectomy for hypercortisolism (study patients) or hyperaldosteronism
(control patients). A standard POD1-CST protocol was used. Hydrocortisone was
started for clinical evidence of AI, basal plasma cortisol <= 5 (MUg/dL), or a
stimulated plasma cortisol <18. RESULTS: A normal POD1-CST was found in all nine
control patients and 11 of 22 patients (50%) with Cushing's syndrome; the other
11 study patients (50%) received GR based on the POD1-CST. These patients were
younger (51 vs 62 years; P = .017), had a higher body mass index (BMI; 31 vs 29
kg/m(2)), and smaller adrenal neoplasms (16.9 vs 33.0 g; P = .009) than non-GR
study patients. CONCLUSION: After unilateral adrenalectomy for hypercortisolism,
only 50% of patients received GR. No preoperative biochemical characteristics
were associated with postoperative AI, although patients who received GR were
younger, and tended to have a higher BMI and smaller adrenal nodules. Use of this
novel protocol for postoperative dynamic adrenal function testing prevented
unnecessary GR in 50% of patients and allowed for individualized patient care.
PMID- 26422768
TI - A case of epidermoid cyst in an intrapancreatic accessory spleen mimicking
pancreas neoplasms: MRI with DWI.
AB - We report on a rare case of an epidermoid cyst in an intrapancreatic accessory
spleen (ECIAS) that presented as a cystic lesion in the tail of the pancreas, in
a 21-year-old woman. ECIAS is very rare; thus, accurate diagnosis before surgery
is difficult. When a wall within the lesion presents with similar imaging
features to accessory splenic tissues on magnetic resonance imaging with
diffusion-weighted imaging, ECIAS should be considered in the differential
diagnosis of cystic lesions in the tail of the pancreas.
PMID- 26422769
TI - MRI safety: a report of current practice and advancements in patient preparation
and screening.
AB - MRI offers detailed diagnostic images without ionizing radiation; however, there
are considerable safety concerns associated with high electromagnetic field
strength. With increasing use of high and ultra high (7T) magnetic field
strength, adequate patient preparation and screening for ferrous material is
increasingly important. We review current safety standards for patient screening
and preparation and how they are implemented at our institution. In addition, we
describe a novel supplemental screening technique wherein the lights are dimmed
in response to detected ferrous metal at the threshold of Zone IV.
PMID- 26422770
TI - Influence of sonication conditions on the efficiency of ultrasonic cleaning with
flowing micrometer-sized air bubbles.
AB - This paper describes the sizes of cleaned areas under different sonication
conditions with the addition of flowing micrometer-sized air bubbles. The
differences in the cleaned area of a glass plate pasted with silicon grease as a
dirty material under different sonication conditions were investigated after tiny
bubbles were blown on the dirty plate placed in an underwater sound field. The
ultrasound was applied perpendicular to the bubble flow direction. The shape of
the cleaned areas was nearly elliptical, so the lengths of the minor and major
axes were measured. The length of the minor axis under sweep conditions
(amplitude modulation), for which the average power was lower than that for
continuous wave (CW) irradiation, was comparable to that for CW irradiation and
was slightly larger than under bubble flow only. Not only the relatively high
power for CW irradiation, but also the larger angular change of the bubble flow
direction under sweep conditions contributed to the enlargement of the cleaned
area in the direction of the minor axis. The combination of bubble flow and
sonication under sweep or CW conditions produced a larger cleaned area compared
with bubble flow only, although the increase was not higher than 20%. A rapid
change from an air to water interface caused by the bubble flow and water jets
caused by the collapse of bubbles due to violent pulsation is the main cleaning
mechanism under a combination of ultrasound and bubble flow.
PMID- 26422771
TI - Is Caenorhabditis elegans the Magic Bullet for Anthelminthic Drug Discovery?
AB - Recent advances in handling and readout have facilitated high-throughput screens
with Caenorhabditis elegans. A new study demonstrates that C. elegans is a useful
tool in high-throughput anthelminthic drug discovery. Despite challenges, drug
discovery using C. elegans offers opportunities that might lead the way to novel
anthelminthic drugs.
PMID- 26422767
TI - A therapeutic-only versus prophylactic platelet transfusion strategy for
preventing bleeding in patients with haematological disorders after
myelosuppressive chemotherapy or stem cell transplantation.
AB - BACKGROUND: Platelet transfusions are used in modern clinical practice to prevent
and treat bleeding in thrombocytopenic patients with bone marrow failure.
Although considerable advances have been made in platelet transfusion therapy in
the last 40 years, some areas continue to provoke debate, especially concerning
the use of prophylactic platelet transfusions for the prevention of
thrombocytopenic bleeding.This is an update of a Cochrane review first published
in 2004 and updated in 2012 that addressed four separate questions: therapeutic
only versus prophylactic platelet transfusion policy; prophylactic platelet
transfusion threshold; prophylactic platelet transfusion dose; and platelet
transfusions compared to alternative treatments. We have now split this review
into four smaller reviews looking at these questions individually; this review is
the first part of the original review. OBJECTIVES: To determine whether a
therapeutic-only platelet transfusion policy (platelet transfusions given when
patient bleeds) is as effective and safe as a prophylactic platelet transfusion
policy (platelet transfusions given to prevent bleeding, usually when the
platelet count falls below a given trigger level) in patients with haematological
disorders undergoing myelosuppressive chemotherapy or stem cell transplantation.
SEARCH METHODS: We searched for randomised controlled trials (RCTs) in the
Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 6),
MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion
Evidence Library (from 1950) and ongoing trial databases to 23 July 2015.
SELECTION CRITERIA: RCTs involving transfusions of platelet concentrates prepared
either from individual units of whole blood or by apheresis, and given to prevent
or treat bleeding in patients with malignant haematological disorders receiving
myelosuppressive chemotherapy or undergoing HSCT. DATA COLLECTION AND ANALYSIS:
We used standard methodological procedures expected by The Cochrane
Collaboration. MAIN RESULTS: We identified seven RCTs that compared therapeutic
platelet transfusions to prophylactic platelet transfusions in haematology
patients undergoing myelosuppressive chemotherapy or HSCT. One trial is still
ongoing, leaving six trials eligible with a total of 1195 participants. These
trials were conducted between 1978 and 2013 and enrolled participants from fairly
comparable patient populations. We were able to critically appraise five of these
studies, which contained separate data for each arm, and were unable to perform
quantitative analysis on one study that did not report the numbers of
participants in each treatment arm.Overall the quality of evidence per outcome
was low to moderate according to the GRADE approach. None of the included studies
were at low risk of bias in every domain, and all the studies identified had some
threats to validity. We deemed only one study to be at low risk of bias in all
domains other than blinding.Two RCTs (801 participants) reported at least one
bleeding episode within 30 days of the start of the study. We were unable to
perform a meta-analysis due to considerable statistical heterogeneity between
studies. The statistical heterogeneity seen may relate to the different methods
used in studies for the assessment and grading of bleeding. The underlying
patient diagnostic and treatment categories also appeared to have some effect on
bleeding risk. Individually these studies showed a similar effect, that a
therapeutic-only platelet transfusion strategy was associated with an increased
risk of clinically significant bleeding compared with a prophylactic platelet
transfusion policy. Number of days with a clinically significant bleeding event
per participant was higher in the therapeutic-only group than in the prophylactic
group (one RCT; 600 participants; mean difference 0.50, 95% confidence interval
(CI) 0.10 to 0.90; moderate-quality evidence). There was insufficient evidence to
determine whether there was any difference in the number of participants with
severe or life-threatening bleeding between a therapeutic-only transfusion policy
and a prophylactic platelet transfusion policy (two RCTs; 801 participants; risk
ratio (RR) 4.91, 95% CI 0.86 to 28.12; low-quality evidence). Two RCTs (801
participants) reported time to first bleeding episode. As there was considerable
heterogeneity between the studies, we were unable to perform a meta-analysis.
Both studies individually found that time to first bleeding episode was shorter
in the therapeutic-only group compared with the prophylactic platelet transfusion
group.There was insufficient evidence to determine any difference in all-cause
mortality within 30 days of the start of the study using a therapeutic-only
platelet transfusion policy compared with a prophylactic platelet transfusion
policy (two RCTs; 629 participants). Mortality was a rare event, and therefore
larger studies would be needed to establish the effect of these alternative
strategies. There was a clear reduction in the number of platelet transfusions
per participant in the therapeutic-only arm (two RCTs, 991 participants;
standardised mean reduction of 0.50 platelet transfusions per participant, 95% CI
-0.63 to -0.37; moderate-quality evidence). None of the studies reported quality
of life. There was no evidence of any difference in the frequency of adverse
events, such as transfusion reactions, between a therapeutic-only and
prophylactic platelet transfusion policy (two RCTs; 991 participants; RR 1.02,
95% CI 0.62 to 1.68), although the confidence intervals were wide. AUTHORS'
CONCLUSIONS: We found low- to moderate-grade evidence that a therapeutic-only
platelet transfusion policy is associated with increased risk of bleeding when
compared with a prophylactic platelet transfusion policy in haematology patients
who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT. There is
insufficient evidence to determine any difference in mortality rates and no
evidence of any difference in adverse events between a therapeutic-only platelet
transfusion policy and a prophylactic platelet transfusion policy. A therapeutic
only platelet transfusion policy is associated with a clear reduction in the
number of platelet components administered.
PMID- 26422772
TI - Releasing the Brake on IFN-gamma Signaling on Infection.
AB - Toxoplasma gondii effectively inhibits the responsiveness of its host cell to
interferon gamma (IFN-gamma). Using a genome-wide genetic screen, Beiting and
colleagues have recently identified coactivators of the transcription factor
STAT1 that can diminish this inhibitory effect. One of these coactivators, TLX,
enhances type 1 helper (Th1) immune responses and restricts parasite replication
during chronic toxoplasmosis.
PMID- 26422773
TI - Climate and Population Immunity in Malaria Dynamics: Harnessing Information from
Endemicity Gradients.
AB - It is clear that climate variability and climate change influence malaria in low
transmission regions. Much less understood is how climate forcing interacts with
population immunity as one moves towards higher transmission intensity. The same
transmission model confronted to time series data from two contrasting
intensities helps unravel this interaction.
PMID- 26422774
TI - Time trends and case fatality rate of in-hospital treated pulmonary embolism
during 11 years of observation in Northwestern Italy.
AB - Pulmonary embolism (PE) is a common disorder with high mortality and morbidity
rates. However, population-based information on its incidence and prognosis
remains limited. We conducted a large epidemiology study collecting data on
hospitalisation for PE (from 2002 to 2012) in a population of about 13 million
people in Northwestern Italy. Patients were identified using the ICD-9-CM codes:
415.11, 415.19; gender and age specific incidence rate of PE during the study
period were estimated using the resident population for each year of the study.
Furthermore, time trends in the in-hospital PE-related mortality and case
fatality rate were calculated. Results were adjusted for possible confounders. A
total of 60,853 patients (mean age 72.8 years, +/- 14.1, 59.6% females) with PE
were included; the overall crude incidence rate for the entire study period was
55.4 and 40.6 events per year per 100,000 inhabitants for women and men,
respectively (p <0.001). However, this difference was completely lost after
standardisation for age. The incidence of PE significantly increased in both
genders during the study period. In-hospital case fatality rate significantly
decreased throughout the study period (p < 0.001) in women (from 15.6% to 10.2%)
and in men (from 17.6% to 10.1%). The observed decrease of the in-hospital case
fatality throughout the study period remained significant also after adjustment
for possible confounders. In conclusion, time trends over an 11-year period show
an increasing incidence of PE, but a significant reduction in mortality during
hospitalisation. Reduction in the case fatality rate remained significant after
adjustment for these possible confounders.
PMID- 26422775
TI - Nano-sized polystyrene affects feeding, behavior and physiology of brine shrimp
Artemia franciscana larvae.
AB - Nano-sized polymers as polystyrene (PS) constitute one of the main challenges for
marine ecosystems, since they can distribute along the whole water column
affecting planktonic species and consequently disrupting the energy flow of
marine ecosystems. Nowadays very little knowledge is available on the impact of
nano-sized plastics on marine organisms. Therefore, the present study aims to
evaluate the effects of 40nm anionic carboxylated (PS-COOH) and 50nm cationic
amino (PS-NH2) polystyrene nanoparticles (PS NPs) on brine shrimp Artemia
franciscana larvae. No signs of mortality were observed at 48h of exposure for
both PS NPs at naplius stage but several sub-lethal effects were evident. PS-COOH
(5-100MUg/ml) resulted massively sequestered inside the gut lumen of larvae (48h)
probably limiting food intake. Some of them were lately excreted as fecal pellets
but not a full release was observed. Likewise, PS-NH2 (5-100ug/ml) accumulated in
larvae (48h) but also adsorbed at the surface of sensorial antennules and
appendages probably hampering larvae motility. In addition, larvae exposed to PS
NH2 undergo multiple molting events during 48h of exposure compared to controls.
The activation of a defense mechanism based on a physiological process able to
release toxic cationic NPs (PS-NH2) from the body can be hypothesized. The
general observed accumulation of PS NPs within the gut during the 48h of exposure
indicates a continuous bioavailability of nano-sized PS for planktonic species as
well as a potential transfer along the trophic web. Therefore, nano-sized PS
might be able to impair food uptake (feeding), behavior (motility) and physiology
(multiple molting) of brine shrimp larvae with consequences not only at organism
and population level but on the overall ecosystem based on the key role of
zooplankton on marine food webs.
PMID- 26422776
TI - Distinguishing the Photothermal and Photoinjection Effects in Vanadium Dioxide
Nanowires.
AB - Vanadium dioxide (VO2) has drawn significant attention for its unique metal-to
insulator transition near the room temperature. The high electrical resistivity
below the transition temperature (~68 degrees C) is a result of the strong
electron correlation with the assistance of lattice (Peierls) distortion.
Theoretical calculations indicated that the strong interelectron interactions
might induce intriguing optoelectronic phenomena, such as the multiple exciton
generation (MEG), a process desirable for efficient optoelectronics and
photovoltaics. However, the resistivity of VO2 is quite temperature sensitive,
and therefore, the light-induced conductivity in VO2 has often been attributed to
the photothermal effects. In this work, we distinguished the photothermal and
photoinjection effects in VO2 nanowires by varying the chopping frequency of the
optical illumination. We found that, in our VO2 nanowires, the relatively slow
photothermal processes can be well suppressed when the chopping frequency is >2
kHz, whereas the fast photoinjection component (direct photoexcitation of charge
carriers) remains constant at all chopping frequencies. By separating the
photothermal and photoinjection processes, our work set the basis for further
studies of carrier dynamics under optical excitations in strongly correlated
materials.
PMID- 26422777
TI - Anesthetic management of patients undergoing resection of carcinoid metastasis to
the brain.
AB - BACKGROUND: Carcinoid tumors are derived from enterochromaffin cells and may
release physiologically active compounds into the systemic circulation, leading
to the development of carcinoid syndrome. Occasionally, these tumors metastasize
to the brain, warranting biopsy or resection. In these surgical patients, the
perioperative implications for anesthetic management are not heretofore defined
in the indexed literature. METHODS: Patients who had craniotomy for biopsy or
resection of intracranial carcinoid tumors were retrospectively identified at a
single medical center. Patient demographics, perioperative anesthetic management,
adverse events, and outcome were summarized in this case series. RESULTS: Eleven
patients were identified; median age was 60 years (range = 42-78 years), and 45%
were male. Immediately before surgery, 4 patients (36%) were receiving a
somatostatin analog drug, and no patient had unchecked carcinoid syndrome. All
patients received general anesthesia that included inhaled isoflurane and nitrous
oxide, and all had invasive arterial blood pressure monitoring. One patient
developed sustained hypotension after induction of anesthesia, likely related to
hypovolemia and anesthetic drugs, but the possibility of carcinoid mediator
release cannot be excluded. There were no other signs or symptoms of carcinoid
syndrome in this or any other patient. Of all 11 patients, 10 (91%) experienced
either significant disease progression (n = 2; 18%) or death (n = 8; 73%) from
carcinoid disease, its sequelae, or an undetermined cause within 3 years after
surgery. Of note, 3 of the deaths occurred shortly after surgery, on
postoperative days 3, 7, and 8. CONCLUSIONS: In our experience, carcinoid tumor
metastasis to the brain-whether because of tumor makeup or prior treatment-is
unlikely to produce symptoms of new-onset carcinoid syndrome intraoperatively;
however, the risk cannot be completely excluded. Postsurgical prognosis was poor,
both within the hospital and after hospital discharge.
PMID- 26422778
TI - The Effect of a Golden Hour Policy on the Morbidity and Mortality of Combat
Casualties.
AB - IMPORTANCE: The term golden hour was coined to encourage urgency of trauma care.
In 2009, Secretary of Defense Robert M. Gates mandated prehospital helicopter
transport of critically injured combat casualties in 60 minutes or less.
OBJECTIVES: To compare morbidity and mortality outcomes for casualties before vs
after the mandate and for those who underwent prehospital helicopter transport in
60 minutes or less vs more than 60 minutes. DESIGN, SETTING, AND PARTICIPANTS: A
retrospective descriptive analysis of battlefield data examined 21,089 US
military casualties that occurred during the Afghanistan conflict from September
11, 2001, to March 31, 2014. Analysis was conducted from September 1, 2014, to
January 21, 2015. MAIN OUTCOMES AND MEASURES: Data for all casualties were
analyzed according to whether they occurred before or after the mandate. Detailed
data for those who underwent prehospital helicopter transport were analyzed
according to whether they occurred before or after the mandate and whether they
occurred in 60 minutes or less vs more than 60 minutes. Casualties with minor
wounds were excluded. Mortality and morbidity outcomes and treatment capability
related variables were compared. RESULTS: For the total casualty population, the
percentage killed in action (16.0% [386 of 2411] vs 9.9% [964 of 9755]; P < .001)
and the case fatality rate ([CFR] 13.7 [469 of 3429] vs 7.6 [1344 of 17,660]; P <
.001) were higher before vs after the mandate, while the percentage died of
wounds (4.1% [83 of 2025] vs 4.3% [380 of 8791]; P = .71) remained unchanged.
Decline in CFR after the mandate was associated with an increasing percentage of
casualties transported in 60 minutes or less (regression coefficient, -0.141; P <
.001), with projected vs actual CFR equating to 359 lives saved. Among 4542
casualties (mean injury severity score, 17.3; mortality, 10.1% [457 of 4542])
with detailed data, there was a decrease in median transport time after the
mandate (90 min vs 43 min; P < .001) and an increase in missions achieving
prehospital helicopter transport in 60 minutes or less (24.8% [181 of 731] vs
75.2% [2867 of 3811]; P < .001). When adjusted for injury severity score and time
period, the percentage killed in action was lower for those critically injured
who received a blood transfusion (6.8% [40 of 589] vs 51.0% [249 of 488]; P <
.001) and were transported in 60 minutes or less (25.7% [205 of 799] vs 30.2% [84
of 278]; P < .01), while the percentage died of wounds was lower among those
critically injured initially treated by combat support hospitals (9.1% [48 of
530] vs 15.7% [86 of 547]; P < .01). Acute morbidity was higher among those
critically injured who were transported in 60 minutes or less (36.9% [295 of 799]
vs 27.3% [76 of 278]; P < .01), those severely and critically injured initially
treated at combat support hospitals (severely injured, 51.1% [161 of 315] vs
33.1% [104 of 314]; P < .001; and critically injured, 39.8% [211 of 530] vs 29.3%
[160 of 547]; P < .001), and casualties who received a blood transfusion (50.2%
[618 of 1231] vs 3.7% [121 of 3311]; P < .001), emphasizing the need for timely
advanced treatment. CONCLUSIONS AND RELEVANCE: A mandate made in 2009 by
Secretary of Defense Gates reduced the time between combat injury and receiving
definitive care. Prehospital transport time and treatment capability are
important factors for casualty survival on the battlefield.
PMID- 26422779
TI - Age: An effect modifier of the association between allergic rhinitis and Otitis
media with effusion.
AB - OBJECTIVES/HYPOTHESIS: 1) To determine whether there is a significant
relationship between allergic rhinitis and otitis media with effusion (OME),
Eustachian tube dysfunction (ETD), or tympanic membrane retraction (TMR) in
children in a nationally representative population; and 2) to determine whether
age is an effect modifier of any such association because this hypothesis has yet
to be tested. STUDY DESIGN: Retrospective analysis of cross-sectional national
databases with limited potential for referral bias. SETTING AND SUBJECTS:
National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical
Care Survey, 2005-2010. METHODS: Univariate, multivariate, stratified, and
subgroup analyses were performed as defined a priori. The primary outcomes were
OME, ETD, or TMR; the primary predictor variable was allergic rhinitis, with age
evaluated as an effect modifier. RESULTS: Data representing 1,491,045,375
pediatric visits were examined and demonstrated that age was an effect modifier
of the assessed association. More specifically, in children 6 years of age or
older, the presence of allergic rhinitis significantly increased the odds of OME,
ETD, or TMR (odds ratio [OR] 4.20; 95% confidence interval [CI] 2.17, 8.09; P <
0.001), whereas in children less than 6 years of age there was no significant
association (OR 1.13; 95% CI 0.53, 2.46; P = 0.745). CONCLUSION: Age is an effect
modifier of the association between allergic rhinitis and OME; a significant
relationship is observed in children 6 years of age and older, whereas there is
no significant association in younger children. LEVEL OF EVIDENCE: 2c.
Laryngoscope, 126:1687-1692, 2016.
PMID- 26422780
TI - A Concise and Highly Enantioselective Total Synthesis of (+)-anti- and (-)-syn
Mefloquine Hydrochloride: Definitive Absolute Stereochemical Assignment of the
Mefloquines.
AB - A concise asymmetric (>99:1 e.r.) total synthesis of (+)-anti- and (-)-syn
mefloquine hydrochloride from a common intermediate is described. The key
asymmetric transformation is a Sharpless dihydroxylation of an olefin that is
accessed in three steps from commercially available materials. The Sharpless
derived diol is converted into either a trans or cis epoxide, and these are
subsequently converted into (+)-anti- and (-)-syn-mefloquine, respectively. The
synthetic (+)-anti- and (-)-syn-mefloquine samples were derivatized with (S)-(+)
mandelic acid tert-butyldimethylsilyl ether, and a crystal structure of each
derivative was obtained. These are the first X-ray structures for mefloquine
derivatives that were obtained by coupling to a known chiral, nonracemic
compound, and provide definitive confirmation of the absolute stereochemistry of
(+)-anti- as well as (-)-syn-mefloquine.
PMID- 26422781
TI - Frequency of Tobacco Use Among Middle and High School Students--United States,
2014.
AB - The use of tobacco products during adolescence increases the risk for adverse
health effects and lifelong nicotine addiction. In 2014, an estimated 4.6 million
middle and high school students were current users of any tobacco product, of
whom an estimated 2.2 million were current users of two or more types of tobacco
products. Symptoms of nicotine dependence are increased for multiple tobacco
product users compared with single-product users. CDC and the Food and Drug
Administration (FDA) analyzed data from the 2014 National Youth Tobacco Survey
(NYTS) to determine how frequently (the number of days in the preceding 30 days)
U.S. middle school (grades 6-8) and high school (grades 9-12) students used
cigarettes, e-cigarettes, cigars, and smokeless tobacco products. Among current
users (>=1 day during the preceding 30 days) in high school, frequent use (>=20
days during the preceding 30 days) was most prevalent among smokeless tobacco
users (42.0%), followed by cigarette smokers (31.6%), e-cigarette users (15.5%),
and cigar smokers (13.1%); a similar pattern was observed for those who used
during all 30 days. Among current users in middle school, frequent use was
greatest among smokeless tobacco users (29.2%), followed by cigarette smokers
(20.0%), cigar smokers (13.2%) and e-cigarette users (11.8%). Current use of two
or more types of tobacco products was common, even among students who used
tobacco products 1-5 days during the preceding 30 days: 77.3% for cigar smokers,
76.9% for cigarette smokers, 63.4% for smokeless tobacco users, and 54.8% for e
cigarettes users. Preventing youths from initiating the use of any tobacco
product is important to tobacco use prevention and control strategies in the
United States. Monitoring the frequency and patterns of tobacco use among youths,
including the use of two or more tobacco products, is important to inform
evidence-based interventions to prevent and reduce all forms of tobacco use among
youths.
PMID- 26422782
TI - Risk of hematological toxicities in patients with solid tumors treated with
ramucirumab: a meta-analysis.
AB - BACKGROUND: We performed a meta-analysis of the risk of hematological adverse
events associated with ramucirumab. METHODS: Eligible studies included randomized
Phase II and III trials of patients with solid tumors on ramucirumab, describing
events of anemia, leucopenia, neutropenia, febrile neutropenia and
thrombocytopenia. RESULTS: A total of 11 clinical trials were considered eligible
for the meta-analysis. The relative risks of all-grade anemia, leucopenia,
neutropenia, febrile neutropenia and thrombocytopenia were 0.88 (95% CI: 0.80
0.96; p = 0.007), 1.13 (95% CI: 0.85-1.49; p = 0.41), 1.25 (95% CI: 1.08-1.44; p
= 0.002), 1.63 (95% CI: 1.30-2.06; p < 0.0001), 1.91 (95% CI: 1.52-2.42; p <
0.00001), respectively. CONCLUSION: Our meta-analysis has demonstrated an
increased risk of febrile neutropenia, all-grade and high-grade neutropenia and
thrombocytopenia with ramucirumab-based treatment compared with control.
PMID- 26422783
TI - Classic PCOS phenotype is not associated with deficiency of endogenous vitamin D
and VDR gene polymorphisms rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI),
rs10735810 (FokI): a case-control study of lower Silesian women.
AB - CONTEXT: The role of endogenous vitamin D and vitamin D receptor (VDR) gene
polymorphism in polycystic ovary syndrome (PCOS) is still controversial.
OBJECTIVE: The objective of this study was to investigate for the first time in
women with "classic" PCOS phenotype and healthy controls the role of the serum
endogenous vitamin D level and VDR gene polymorphisms in PCOS etiology. DESIGN:
Ninety-two women with "classic" PCOS phenotype and 85 controls from lower Silesia
with comparable body mass index (BMI) were studied. In all women the waist
circumference, android/gynoid fat deposit, parameters of lipid and glucose
metabolism, testosterone, free androgen index, sex hormone binding globulin
(SHBG) and vitamin D were evaluated. Also, VDR gene polymorphisms rs731236,
rs7975232, rs1544410 and rs10735810 were assessed. RESULTS: Serum vitamin D
levels in both groups were comparable. Also high, comparable frequencies of
hypovitaminosis and vitamin D deficiency in both groups were observed. Women with
"classic" PCOS phenotype had statistically significantly higher values of all
measured parameters, except serum SHBG and high-density lipoprotein (HDL)
cholesterol, which were lower. The frequency of VDR genotype polymorphism was
also comparable in both groups. CONCLUSIONS: For the first time, we show that
endogenous vitamin D deficiency and VDR polymorphisms are not associated with
homogeneous "classic" PCOS phenotype.
PMID- 26422784
TI - [Normal pressure hydrocephalus: A review and practical aspects].
AB - Idiopathic normal pressure hydrocephalus is a chronic disorder affecting the
elderly. It is defined by Adams and Hakim's triad in addition to ventricular
dilation visible by brain imaging and normal cerebrospinal fluid pressure during
lumbar puncture. The objective of this review was to propose a standard of care
for idiopathic normal pressure hydrocephalus based on an extensive literature
review conducted on 459 articles published over the last 10 years. Those articles
were obtained by searching for the keywords "normal pressure hydrocephalus" in
the PubMed database and selecting all the articles published in English or in
French. The diagnosis of idiopathic normal pressure hydrocephalus is difficult
because of commonly associated diseases, such as Alzheimer's disease and
microangiopathy. Brain MRI is one of the key procedures to assist in the
diagnosis of idiopathic normal pressure hydrocephalus. Indeed, the presence of
certain MRI features is highly predictive of a positive tap test and shunt
responsiveness. Nevertheless, tap test remains the standard of care for
diagnosis. Continuous cerebrospinal fluid drainage test is an alternative because
it improves the sensitivity of diagnosis (but is a more complicated test to
perform). Alzheimer's biomarkers dosing in the cerebrospinal fluid seems
interesting when diagnosis remains uncertain: the presence of Alzheimer's profile
of the biological markers is predictive of a lower response to the tap test.
PMID- 26422785
TI - Is there still a place for "old therapies" in the management of immune
thrombocytopenia?
AB - New molecules such as rituximab or thrombopoietin receptor agonists (romiplostim
and eltrombopag) have changed the management of immune thrombocytopenia.
Therefore, old drugs which are less expensive and with a well-known benefit/risk
ratio are being underused. We aim to define the place of dapsone, danazol,
hydroxychloroquine and vinca-alkaloids at the era of targeted therapy in immune
thrombocytopenia. With a response rate around 30% to 50%, dapsone is an
interesting second-line therapy to be used just after corticosteroids. Patients
with positive antinuclear antibodies can benefit from hydroxychloroquine with a
50% response rate. Because of its side effects, mostly virilization, danazol will
be preferentially used in the elderly. Vinca-alkaloids could be temporarily used
in patients that do not respond to intravenous immunoglobulins or to limit their
use to avoid shortage periods.
PMID- 26422786
TI - Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7
carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the
treatment of cancer.
AB - A series of imidazo[4,5-c]pyridine-7-carboxamide derivatives as poly(ADP-ribose)
polymerase (PARP) inhibitors have been developed. All target compounds were
evaluated for their PARP-1 inhibitory activity and some were further assessed for
cellular potency. These efforts led to identification of a novel PARP-1 inhibitor
2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide 11a (XZ
120312). 11a displayed strong inhibition against the PARP-1 enzyme with an IC50
of 8.6+/-0.6 nM and excellent potentiation of temozolomide cytotoxicity in cancer
cell lines SW-620, MDA-MB-468 and A549 by 4.0, 3.0 and 7.7 times, respectively.
PMID- 26422787
TI - Synthesis of novel acridine bis-sulfonamides with effective inhibitory activity
against the carbonic anhydrase isoforms I, II, IX and XII.
AB - By using a multi component reaction system (MCR), nitro acridine sulfonamides
were obtained from cyclic-1,3-diketones, 4-aminobenzene sulfonamide and aromatic
aldehydes. Some novel acridine bis-sulfonamides 6a-l were then synthesized by the
reaction between sulfonyl chlorides and the novel amino-acridine sulfonamides 5a
and 5b, obtained by reduction of nitro-acridine sulfonamide derivatives 4a and
4b. The newly synthesized compounds were investigated as inhibitors of 4 human
carbonic anhydrase isoforms (hCA, EC 4.2.1.1). Several of the compounds showed
low micromolar inhibition against the medically relevant isoforms hCA I, II, IX,
and XII.
PMID- 26422788
TI - Mucin-drugs interaction: The case of theophylline, prednisolone and cephalexin.
AB - The binding of mucin with three commercially available drugs (theophylline,
cephalexin and prednisolone) belonging to different pharmaceutical classes was
investigated. The studied drugs are normally used to treat the symptomatology of
cystic fibrosis. The interaction between drugs and mucin has been investigated
using fluorescence and UV-Vis absorption spectroscopy; quenching mechanism,
binding constants, binding sites, thermodynamic parameters and binding distance
of the interaction were obtained.
PMID- 26422789
TI - In Vitro and In Vivo Plant Growth Promoting Activities and DNA Fingerprinting of
Antagonistic Endophytic Actinomycetes Associates with Medicinal Plants.
AB - Endophytic actinomycetes have shown unique plant growth promoting as well as
antagonistic activity against fungal phytopathogens. In the present study forty
two endophytic actinomycetes recovered from medicinal plants were evaluated for
their antagonistic potential and plant growth-promoting abilities. Twenty-two
isolates which showed the inhibitory activity against at least one pathogen were
subsequently tested for their plant-growth promoting activities and were compared
genotypically using DNA based fingerprinting, including enterobacterial
repetitive intergenic consensus (ERIC) and BOX repetitive elements. Genetic
relatedness based on both ERIC and BOX-PCR generates specific patterns
corresponding to particular genotypes. Exponentially grown antagonistic isolates
were used to evaluate phosphate solubilization, siderophores, HCN, ammonia,
chitinase, indole-3-acetic acid production, as well as antifungal activities. Out
of 22 isolates, the amount of indole-3-acetic acid (IAA) ranging between 10-32
MUg/ml was produced by 20 isolates and all isolates were positive for ammonia
production ranging between 5.2 to 54 mg/ml. Among 22 isolates tested, the amount
of hydroxamate-type siderophores were produced by 16 isolates ranging between 5.2
to 36.4 MUg/ml, while catechols-type siderophores produced by 5 isolates ranging
from 3.2 to 5.4 MUg/ml. Fourteen isolates showed the solubilisation of inorganic
phosphorous ranging from 3.2 to 32.6 mg/100ml. Chitinase and HCN production was
shown by 19 and 15 different isolates, respectively. In addition, genes of indole
acetic acid (iaaM) and chitinase (chiC) were successively amplified from 20 and
19 isolates respectively. The two potential strains Streptomyces sp. (BPSAC34)
and Leifsonia xyli (BPSAC24) were tested in vivo and improved a range of growth
parameters in chilli (Capsicum annuum L.) under greenhouse conditions. This study
is the first published report that actinomycetes can be isolated as endophytes
from within these plants and were shown to have antagonistic and plant growth
promoting abilities. These results clearly suggest the possibility of using
endophytic actinomycetes as bioinoculant for plant growth promotion, nutrient
mobilization or as biocontrol agent against fungal phytopathogens for sustainable
agriculture.
PMID- 26422790
TI - Action in Perception: Prominent Visuo-Motor Functional Symmetry in Musicians
during Music Listening.
AB - Musical training leads to sensory and motor neuroplastic changes in the human
brain. Motivated by findings on enlarged corpus callosum in musicians and
asymmetric somatomotor representation in string players, we investigated the
relationship between musical training, callosal anatomy, and interhemispheric
functional symmetry during music listening. Functional symmetry was increased in
musicians compared to nonmusicians, and in keyboardists compared to string
players. This increased functional symmetry was prominent in visual and motor
brain networks. Callosal size did not significantly differ between groups except
for the posterior callosum in musicians compared to nonmusicians. We conclude
that the distinctive postural and kinematic symmetry in instrument playing cross
modally shapes information processing in sensory-motor cortical areas during
music listening. This cross-modal plasticity suggests that motor training affects
music perception.
PMID- 26422791
TI - Organic Solar Cells Based on a 2D Benzo[1,2-b:4,5-b']difuran-Conjugated Polymer
with High-Power Conversion Efficiency.
AB - A novel 2D benzodifuran (BDF)-based copolymer (PBDF-T1) is synthesized. Polymer
solar cells fabricated with PBDF-T1 show high power conversion efficiency of
9.43% and fill factor of 77.4%, which is higher than the performance of its
benzothiophene (BDT) counterpart (PBDT-T1). These results provide important
progress for BDF-based copolymers and demonstrate that BDF-based copolymers can
be competitive with the well-studied BDT counterparts via molecular structure
design and device optimization.
PMID- 26422792
TI - On the mechanism and optimization of triboelectric nanogenerators.
AB - The mechanism for a triboelectric nanogenerator (TENG) with contacting materials
being different conductors is essentially the same as that of a Kelvin probe. The
difference between the two is that the former is designed for harvesting
mechanical energy while the latter is used for measuring contact potential
differences. The formalism developed for the conductor-conductor TENG can be
equivalently applied to conductor-dielectric and dielectric-dielectric TENGs
under appropriate approximations. The phenomenological parameter of tribo-charge
surface density used in the previous model can also be accounted for in the
current formalism. The dependence of average output power on load resistance and
motion speed is analyzed, and the optimal output power and corresponding
resistance are calculated for different motions. The formula that relates output
power to charge and displacement is given, and based on this formula different
ways to improve output power and load resistance matching have been conceived.
PMID- 26422793
TI - N-acteyl-beta-D-glucosaminidase and kidney injury molecule-1: New predictors for
long-term progression of chronic kidney disease in patients with heart failure.
AB - AIM: Patients with chronic heart failure (CHF) are often characterized by the
cardiorenal syndrome (CRS). The aim of the present study was to assess whether
novel markers of kidney injury are able to predict progression of chronic kidney
disease (CKD) in patients with CHF. METHODS: New renal biomarkers, N-acteyl-beta
D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1) and Neutrophil
Gelatinase-Associated Lipocalin (NGAL), were assessed from urine samples of 149
patients with chronic heart failure. During a 5-year-follow-up, renal function
was assessed by creatinine and estimated glomerular filtration rate (eGFR CKD
EPI) and was available for 138 patients. Further, data regarding all-cause
mortality was obtained. RESULTS: Twenty-six patients (18.8%) developed a
progression of CKD during the follow-up period, as defined by decline in eGFR
category accompanied by a >=25% drop in eGFR form baseline. No difference
regarding age, sex, body mass index, hypertension, diabetes or EF was present
between patients with and without CKD progression (each P = n.s.). At baseline,
creatinine concentrations and eGFR were significantly different between both
groups (sCr: 1.50 +/- 0.67 vs 1.04 +/- 0.37, P = < 0.001; eGFR: 47.8 +/- 12.3 vs.
77.3 +/- 23.5 mL/min per 1.73m(2) , each P < 0.001). In a Kaplan-Meier-analysis,
KIM-1 and NAG were significant predictors for CKD progression (both P < 0.05). In
Cox regression analysis, NAG > median (OR 3.25,P = 0.013), initial eGFR (OR 0.94,
P < 0.001) and diuretic use (OR 3.92, P = 0.001) were independent predictors of
CKD progression. Further, KIM-1 and NAG were also independent predictors of a
combined endpoint of CKD progression and all-cause mortality by Cox regression
analysis (each P < 0.05). The combination of both markers showed additive value
regarding both endpoints. NGAL showed no association with CKD progression.
CONCLUSIONS: During long-term follow-up chronic heart failure patients with CKD
show a relevant disease progression. The current study emphasizes a strong
association of the tubular biomarkers NAG and KIM-1 with CKD progression in
chronic heart failure and suggests their usefulness as cardiorenal markers.
PMID- 26422794
TI - Cloning, expression and biochemical characterization of recombinant superoxide
dismutase from Antarctic psychrophilic bacterium Pseudoalteromonas sp. ANT506.
AB - In this study, a superoxide dismutase gene (PsSOD) from Pseudoalteromonas sp.
ANT506 was cloned and over expressed in Escherichia coli. The PsSOD has an open
reading frame of 582 bp with a putative product of 193 amino acid residue and an
estimated molecular size of 21.4 kDa. His-tagged PsSOD was subsequently purified
12.6-fold by Ni-affinity chromatography and the yield of 22.9%. The
characterization of the purified rPsSOD exhibited maximum activity at 30 degrees
C and pH 8.0. The enzyme exhibited 13.9% activity at 0 degrees C and had high
thermo lability at higher than 50 degrees C. rPsSOD exhibited well capability to
2.5 M NaCl (62.4%). These results indicated that rPsSOD exhibited special
catalytic properties.
PMID- 26422795
TI - Palladium-Based Nanomaterials: A Platform to Produce Reactive Oxygen Species for
Catalyzing Oxidation Reactions.
AB - Oxidation reactions by molecular oxygen (O2 ) over palladium (Pd)-based
nanomaterials are a series of processes crucial to the synthesis of fine
chemicals. In the past decades, investigations of related catalytic materials
have mainly been focused on the synthesis of Pd-based nanomaterials from the
angle of tailoring their surface structures, compositions and supporting
materials, in efforts to improve their activities in organic reactions. From the
perspective of rational materials design, it is imperative to address the
fundamental issues associated with catalyst performance, one of which should be
oxygen activation by Pd-based nanomaterials. Here, the fundamentals that account
for the transformation from O2 to reactive oxygen species over Pd, with a focus
on singlet O2 and its analogue, are introduced. Methods for detecting and
differentiating species are also presented to facilitate future fundamental
research. Key factors for tuning the oxygen activation efficiencies of catalytic
materials are then outlined, and recent developments in Pd-catalyzed oxygen
related organic reactions are summarized in alignment with each key factor. To
close, we discuss the challenges and opportunities for photocatalysis research at
this unique intersection as well as the potential impact on other research
fields.
PMID- 26422796
TI - Serum microRNA-221 functions as a potential diagnostic and prognostic marker for
patients with osteosarcoma.
AB - BACKGROUND: Upregulation of microRNA-221 (miR-221) has been reported to induce
the malignant phenotype of human osteosarcoma, suggesting its potential as a
therapeutic target for this malignancy. However, the role of miR-221 in diagnosis
and prognosis of osteosarcoma has been well less elaborated. Our aim was to
investigate the clinicopathological, diagnostic, and prognostic value of miR-221
in human osteosarcoma. METHODS: Expression levels of miR-221 in tumor tissues and
patients' sera obtained from 108 cases of primary osteosarcomas were detected by
quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR).
RESULTS: Compared with normal controls, the expression levels of miR-221 in
osteosarcoma tissues and patients' sera were both dramatically upregulated (both
P=0.001). Then, receiver operating characteristics (ROC) analysis showed that
serum miR-221 level could efficiently distinguish osteosarcoma patients from
healthy controls (Area Under ROC Curve, AUC=0.844). Additionally, the serum level
of miR-221 in osteosarcoma patients with positive distance metastasis (P=0.01)
and advanced clinical stage (P=0.006) was significantly higher than those without
distance metastasis and with early clinical stage. Moreover, we found that high
serum miR-221 level was correlated with shorter recurrence-free survival (RFS)
and overall survival (OS) than low level (both P=0.001). Multivariate survival
analysis confirmed that serum miR-221 level was an independent prognostic factor
influencing the survival of patients with osteosarcoma. CONCLUSION: These
findings reveal that miR-221 may play a crucial role in the occurrence and the
progression of human osteosarcoma. More importantly, miR-221 may function as a
promising marker for screening individuals with osteosarcoma and for identifying
individuals with poor prognostic potentials.
PMID- 26422797
TI - Challenging integration: clinicians' perspectives of communicating collaboration
in a center for integrative medicine.
AB - A shift has occurred in the provision of health care to include a focus not just
on biology and disease but also on the whole person, preventative care, and an
array of healing modalities based on systems of beliefs and values not typically
included within biomedical practice. This approach to health care, termed
integrative medicine (IM), blends biomedicine with a broader understanding of
patients and their illnesses, including elements of mind, body, and spirit that
may be contributing to an ailment. While the use of integrative medicine has
increased and centers for integrative medicine have proliferated within
conventional health care organizations, distinct tensions arise from this
amalgamation. The tensions between IM and biomedical clinicians often center on
their differing training and philosophies, as well as on a larger system of
health care that privileges biomedicine. As a result, this research is designed
to explore the challenges IM clinicians face in collaborating with conventional
practitioners to provide patient care. Analysis of interviews with 14 clinicians
at one center for integrative medicine revealed four specific challenges they
face in their attempt to co-practice IM with conventional medicine. The four
challenges include (a) challenges to collaboration, (b) challenges to legitimacy,
(c) challenges to consistency, and (d) challenges to unification. Future research
should investigate the ways in which these challenges can be addressed so that
collaboration throughout the system is facilitated. The professional training of
clinicians, the structuring and institutionalization of integrative medicine, and
enhanced systems for communicating patient information all play a significant
role in this transformation.
PMID- 26422798
TI - The influence of thermal processing on the fatty acid profile of pork and lamb
meat fed diet with increased levels of unsaturated fatty acids.
AB - The research was carried out on 32 crossbred pigs of Polish Large White * Danish
Landrace with Duroc and 80 rams, crossbreds of the Prolific-Dairy Koludzka Sheep
with the Ile de France, a meat sheep. The fodder for the animals was enriched
with the unsaturated fatty acids originated mainly from linseed and rapeseed
oils. The fatty acid profile was determined in cooked longissimus lumborum,
roasted triceps brachii and raw ripened rump from pigs as well as in grilled
lambs' legs and their corresponding raw materials. Roasting caused the most
pronounced increase of the saturated fatty acids and decrease in the
polyunsaturated fatty acids of heated pork muscles. The smallest changes were
observed in grilled lamb legs. The heating processes applied in this study, in
most cases, did not cause essential changes in the indices of pro-health
properties of fatty acid, therefore meat in the majority fulfil the latest
recommendations of EFSA and FAO/WHO according to human health.
PMID- 26422799
TI - Neural circuits underlying motor facilitation during observation of implied
motion.
AB - In the present study we used single and paired-pulse Transcranial Magnetic
Stimulation (TMS) to evaluate the effect of implied motion on primary motor
cortex microcircuits. We found that observation of the implied motion of a static
image increases MEP amplitude and reduces short-interval intracortical inhibition
(SICI), without significant modulation of intracortical facilitation and sensory
motor integration. Our results add to the existing literature on the activation
of the observation-execution matching system and describe a selective modulation
of GABAergic cortical microcircuits during observation of implied motion.
PMID- 26422800
TI - Effect of Time after Anterior Cruciate Ligament Tears on Proprioception and
Postural Stability.
AB - This study was designed to compare proprioception and postural stability in
patients with acute (time from injury <= 3 months) and chronic (time from injury
> 3 months) ACL tears, and to evaluate the correlation between time interval
after ACL injury and proprioception. Thigh muscle strength, postural stability,
and joint position sense were compared in 48 patients with acute ACL tears and in
28 with chronic ACL tears. Maximal torque (60 degrees /sec) of the quadriceps and
hamstring was evaluated using an isokinetic testing device. Postural stability
was determined from the anterior-posterior (APSI), medial-lateral (MLSI), and
overall (OSI) stability indices using stabilometry. Joint position sense was also
tested by reproduction of passive positioning (RPP). Muscle strengths and
stability indices on both the involved and uninvolved sides were similar in the
acute and chronic ACL tear groups. RPP on the involved side was significantly
greater in the chronic than in the acute ACL tear group (7.8 degrees vs. 5.6
degrees , P = 0.041). Two of three stability indices (APSI, OSI) and RPP were
significantly greater on the involved than the uninvolved side in the chronic ACL
tear group.
PMID- 26422801
TI - Neurobehavioral development prior to term-age of preterm infants and acute
stressful events during neonatal hospitalization.
AB - BACKGROUND: Neonatal Intensive Care Units (NICUs) protect preterm infants;
otherwise, this is a stressful environment including painful stimuli. AIMS: To
compare early neurobehavioral development prior to term-age in preterm infants at
34-36weeks of post-conceptional age in different gestational ages, and to examine
the effects of prematurity level and acute stressful events during NICU
hospitalization on neurobehavioral development. STUDY DESIGN: Cross-sectional
design. SUBJECTS: Forth-five preterm infants, 34-36weeks of post-conceptional
age, were distributed into groups: extreme preterm (EPT; 23-28weeks of
gestational age; n=10), moderate preterm (MPT; 29-32weeks of gestational age;
n=10), late preterm (LPT; 34-36weeks of gestational age; n=25). OUTCOME MEASURES:
All of the neonates were evaluated using the Neurobehavioral Assessment of
Preterm Infant (NAPI) prior to 37weeks of post-conceptional age. The Neonatal
Infant Stressor Scale (NISS) was applied for EPT and MPT infants during NICU
hospitalization, and medical charts were analyzed. RESULTS: The EPT group
experienced significantly more acute stressful events during NICU hospitalization
than the MPT group. The MPT group had lower scores in motor development and vigor
than the EPT and LPT group, and they exhibited poorer quality crying than the LPT
group. Motor development and vigor and alertness and orientation in preterm
infants were predicted by prematurity level and acute stressful events.
CONCLUSION: The extreme preterm was exposed to higher stressful experiences than
moderate and late preterm infants. However, the moderate preterm infants
presented more vulnerable than the other counterparts in motor and vigor
outcomes.
PMID- 26422802
TI - Bacterial membrane vesicles, an overlooked environmental colloid: Biology,
environmental perspectives and applications.
AB - Phospholipid vesicles play important roles in biological systems. Bacteria are
one of the most abundant organisms on Earth, and bacterial membrane vesicles
(MVs) were first observed 50 years ago. Many bacteria release MVs to the
environment that mainly consist of the cell membrane and typically range from 20
to 400 nm in size. Bacterial MVs are involved in several biological functions,
such as delivery of cargo, virulence and gene transfer. MVs can be isolated from
laboratory culture and directly from the environment, indicating their high
abundance in and impact on ecosystems. Many colloidal particles in the
environment ranging in size from 1 nm to 1 MUm have been reported but not
characterized at the molecular level, and MVs remain to be explored. Hence, MVs
can be considered terra incognita in environmental colloid research. Although MV
biogenesis and biological roles are yet to be fully understood, the accumulation
of knowledge has opened new avenues for their applications. Via genetic
engineering, the MV yield can be greatly increased, and the components of MVs can
be tailored. Recent studies have demonstrated that MVs have promising potential
for applications such as drug delivery systems and nanobiocatalysts. For
instance, MV vaccines have been extensively studied and have already been
approved in Europe. Recent MV studies have evoked great interest in the fields of
biology and biotechnology, but fundamental questions, such as their transport in
the environment or physicochemical features of MVs, remain to be addressed. In
this review, we present the current understanding of bacterial MVs and
environmental perspectives and further introduce their applications.
PMID- 26422803
TI - Airway Covered Metallic Stent Based on Different Fistula Location and Size in
Malignant Tracheoesophageal Fistula.
AB - BACKGROUND: Malignant tracheoesophageal fistula (MTEF) is a devastating
complication of esophageal cancer, lung cancer or other carcinoma with a shorter
life-span and poor life quality. The aim of this study was to assess the effect
of airway stent insertion on MTEF patients. METHODS: A total of 63 MTEF patients
were included, 12 patients with lung cancer and 46 patients with esophageal
cancers. Eight zones were proposed to classify various fistula locations. Airway
stents were selected based on the various zones and fistula size. RESULTS: Airway
stents were successfully inserted in all patients, and both airway and esophageal
stents in 8 patients. Most fistula were located in locations II (18/63, 28.6%),
III (22/63, 34.9%), then VII (9/63, 14.3%). The stents included 10 (15.9%) I
shaped, 8 (12.7%) L shaped and 45 (71.4%) Y shaped. Different stents were placed
based on different locations and sizes of fistulas. Overall, mean survival time
was 163 days (2-270 days). Most symptoms relieved after stent insertion. Mean
Karnofsky score jumped from 43.0 +/- 10.7 before stent placement to 66.7 +/- 10.8
after stent insertion (P = 0.000). Complete closure was achieved in 45 patients
(71.4%), and incomplete closure and leakage were found in 18 patients.
CONCLUSIONS: Airway stent insertion provides an effective approach to improve
symptoms and quality of life. The choice of stent based on different fistula
location and size may be a reasonable way in clinical practice.
PMID- 26422804
TI - Severe Azotemia and Hyperchloremic Metabolic Acidosis Associated With Reverse
Flow Enterovesical Fistula.
PMID- 26422805
TI - Future directions in human-environment research.
AB - Human-environment research in the 21st century will need to change in major ways.
It will need to integrate the natural and the social sciences; it will need to
engage stakeholders and citizens in the design of research and in the delivery of
science for the benefit of society; it will need to address ethical and
democratic goals; and it will need to address a myriad of important theoretical
and methodological challenges that continue to impede progress in the advance of
sustainability science.
PMID- 26422806
TI - Erratum: "Pollinator Power: Nutrition Security Benefits of an Ecosystem Service".
PMID- 26422808
TI - Properties of noncovalent tetraphenylporphine...C60 dyads as studied by different
long-range and dispersion-corrected DFT functionals.
AB - The noncovalent dyad of tetraphenylporphine and C60 fullerene (H2TPP...C60) and
the tetraphenylporphine dimer (H2TPP...H2TPP) were studied by density functional
theory (DFT), using functionals that incorporate empirical dispersion correction
(DFT-D), functionals that use a long-range correction (LC) scheme, a hybrid
functional (B3LYP) and a highly parametrized empirical exchange-correlation
functional (M05-2X). The results were compared to X-ray structures and
interaction energies reported in previous experimental and theoretical studies.
It was found that B3LYP and CAM-B3LYP functionals fail to reproduce the X-ray
structures and binding energies of the TPP...C60 system. DFT-D functionals
overestimated the pi...pi energy interactions for both systems, however, the
optimized structures agree well with those observed experimentally. The LC-BLYP
functional predicts geometries similar to X-ray structures; nevertheless, due to
the lack of correction in the dispersion energy, the predicted energies for both
model systems are low. On the other hand, the M05-2X functional exhibited the
best performance. Both the structures and binding energies calculated with M05-2X
are consistent with experimental and theoretical evidence reported by other
authors, as well as with our experimental results obtained by means of atomic
force microscopy on H2TPP thin films grown on the HOPG/C60 substrate by physical
vapor deposition.
PMID- 26422807
TI - Weight gain and changes in plasma adiponectin and leptin concentrations after 12
month insulin intensive therapy for Chinese male patients with newly diagnosed
type 2 diabetes.
AB - AIM: To examine the effects of intensive insulin therapy (IIT) in Chinese male
patients with newly diagnosed type 2 diabetes in 12 months on plasma adiponectin
and leptin levels and to assess whether changes in plasma adiponectin and leptin
could be associated with subsequent weight gain or not. METHODS: Overall 84
patients were taken IIT. Total, and high-, and low-molecular-weight (HMW, LMW)
adiponectin and leptin concentrations were measured at the time of study
inclusion, days 7, and 1, 3, 6 and 12 months after IIT, respectively. Patients'
body weight was recorded every time when adiponectin and leptin were measured.
RESULTS: With improvement of diabetes control, plasma total and HMW adiponectin
and leptin concentrations increased from inclusion to 3 months significantly and
progressively, but remained steady after 6 months. Weight increased relatively
modestly with a mean gain of 2kg for 12 months. Moreover, higher increments of
total and HMW adiponectin from inclusion to 12 months were associated with
significantly less subsequent weight gain after adjustment for confounding
factors: the patients in the lowest tertile of total adiponectin increased by
2.47kg compared to patients in the highest tertile who increased by 0.56kg (P
value=0.006). Whereas, the higher increments of leptin levels under the same
condition were linked with more subsequent weight gain significantly (P
value=0.003). CONCLUSIONS: Our researches suggest that glycaemic control with IIT
increases total and HMW adiponectin and leptin in newly diagnosed type 2 diabetes
male patients, the elevation of total and HMW adiponectin and leptin levels may
predict weight gain after IIT.
PMID- 26422810
TI - Late-Breaking Abstracts: 57th Annual Scientific Meeting of the American Headache
Society.
PMID- 26422809
TI - Role of Lipid Blooming and Crystallite Size in the Performance of Highly Soluble
Drug-Loaded Microcapsules.
AB - Hot-melt coating is of growing interest, because it does not require solvents,
resulting in reduced process times and costs. However, excipients for this
technology are mainly triacylglycerides (TAGs) or their derivatives, which
exhibit polymorphism, surface disruption, and complex crystallite networks,
affecting the release profile of produced microcapsules. In this work, anhydrous
citric acid crystals were coated with molten tristearin using conventional inlet
air temperatures (microcapsules A) and temperatures above the melting point of
alpha-form (microcapsules B). Additionally, microcapsules A were tempered to
achieve polymorphic stability (microcapsules AB). The product yield and coating
efficacy were above 90% and 97%, respectively, demonstrating the feasibility and
efficacy of the process. Small angle X-ray scattering analysis confirmed that the
tristearin shell of microcapsules B is in the beta-form with a larger average
crystallite size than microcapsules A and AB. Scanning electron microscopy images
revealed a nonbloomed surface of microcapsules B. We showed that blooming does
not play a critical role in the drug release, but the apparent diffusion
coefficient of drug is dramatically reduced by increasing TAGs crystallite size
and resulting tortuosity. This work brings new insights on the micrometric
properties of solid lipid dosage forms, being an important step to prevent the
overuse of excipients with unknown toxicity.
PMID- 26422811
TI - Interventions for preventing and treating low-back and pelvic pain during
pregnancy.
AB - BACKGROUND: More than two-thirds of pregnant women experience low-back pain and
almost one-fifth experience pelvic pain. The two conditions may occur separately
or together (low-back and pelvic pain) and typically increase with advancing
pregnancy, interfering with work, daily activities and sleep. OBJECTIVES: To
update the evidence assessing the effects of any intervention used to prevent and
treat low-back pain, pelvic pain or both during pregnancy. SEARCH METHODS: We
searched the Cochrane Pregnancy and Childbirth (to 19 January 2015), and the
Cochrane Back Review Groups' (to 19 January 2015) Trials Registers, identified
relevant studies and reviews and checked their reference lists. SELECTION
CRITERIA: Randomised controlled trials (RCTs) of any treatment, or combination of
treatments, to prevent or reduce the incidence or severity of low-back pain,
pelvic pain or both, related functional disability, sick leave and adverse
effects during pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors
independently assessed trials for inclusion and risk of bias, extracted data and
checked them for accuracy. MAIN RESULTS: We included 34 RCTs examining 5121
pregnant women, aged 16 to 45 years and, when reported, from 12 to 38 weeks'
gestation. Fifteen RCTs examined women with low-back pain (participants = 1847);
six examined pelvic pain (participants = 889); and 13 examined women with both
low-back and pelvic pain (participants = 2385). Two studies also investigated low
back pain prevention and four, low-back and pelvic pain prevention. Diagnoses
ranged from self-reported symptoms to clinicians' interpretation of specific
tests. All interventions were added to usual prenatal care and, unless noted,
were compared with usual prenatal care. The quality of the evidence ranged from
moderate to low, raising concerns about the confidence we could put in the
estimates of effect. For low-back painResults from meta-analyses provided low
quality evidence (study design limitations, inconsistency) that any land-based
exercise significantly reduced pain (standardised mean difference (SMD) -0.64;
95% confidence interval (CI) -1.03 to -0.25; participants = 645; studies = seven)
and functional disability (SMD -0.56; 95% CI -0.89 to -0.23; participants = 146;
studies = two). Low-quality evidence (study design limitations, imprecision) also
suggested no significant differences in the number of women reporting low-back
pain between group exercise, added to information about managing pain, versus
usual prenatal care (risk ratio (RR) 0.97; 95% CI 0.80 to 1.17; participants =
374; studies = two). For pelvic painResults from a meta-analysis provided low
quality evidence (study design limitations, imprecision) of no significant
difference in the number of women reporting pelvic pain between group exercise,
added to information about managing pain, and usual prenatal care (RR 0.97; 95%
CI 0.77 to 1.23; participants = 374; studies = two). For low-back and pelvic
painResults from meta-analyses provided moderate-quality evidence (study design
limitations) that: an eight- to 12-week exercise program reduced the number of
women who reported low-back and pelvic pain (RR 0.66; 95% CI 0.45 to 0.97;
participants = 1176; studies = four); land-based exercise, in a variety of
formats, significantly reduced low-back and pelvic pain-related sick leave (RR
0.76; 95% CI 0.62 to 0.94; participants = 1062; studies = two).The results from a
number of individual studies, incorporating various other interventions, could
not be pooled due to clinical heterogeneity. There was moderate-quality evidence
(study design limitations or imprecision) from individual studies suggesting that
osteomanipulative therapy significantly reduced low-back pain and functional
disability, and acupuncture or craniosacral therapy improved pelvic pain more
than usual prenatal care. Evidence from individual studies was largely of low
quality (study design limitations, imprecision), and suggested that pain and
functional disability, but not sick leave, were significantly reduced following a
multi-modal intervention (manual therapy, exercise and education) for low-back
and pelvic pain.When reported, adverse effects were minor and transient. AUTHORS'
CONCLUSIONS: There is low-quality evidence that exercise (any exercise on land or
in water), may reduce pregnancy-related low-back pain and moderate- to low
quality evidence suggesting that any exercise improves functional disability and
reduces sick leave more than usual prenatal care. Evidence from single studies
suggests that acupuncture or craniosacral therapy improves pregnancy-related
pelvic pain, and osteomanipulative therapy or a multi-modal intervention (manual
therapy, exercise and education) may also be of benefit.Clinical heterogeneity
precluded pooling of results in many cases. Statistical heterogeneity was
substantial in all but three meta-analyses, which did not improve following
sensitivity analyses. Publication bias and selective reporting cannot be ruled
out.Further evidence is very likely to have an important impact on our confidence
in the estimates of effect and change the estimates. Studies would benefit from
the introduction of an agreed classification system that can be used to
categorise women according to their presenting symptoms, so that treatment can be
tailored accordingly.
PMID- 26422812
TI - A molecular simulation study on the adhesion behavior of a functionalized
polyethylene-functionalized graphene interface.
AB - Molecular dynamics simulations were applied to investigate interfacial adhesion
between functionalized polyethylene (fPE) and functionalized graphene (fG)
surfaces. In order to functionalize the PE and graphene surfaces, various types
of functional groups were covalently bonded on the surfaces in a random manner.
Adhesion between fPE and fG surfaces was evaluated by the calculation of work of
separation (Wsep), while the interfaces were not allowed to relax. According to
the simulation results, the combination of the atomic roughness effect and the
electronic properties of the functional groups had influence on the adhesion
between PE and graphene. The effect of surface reorganization was also
investigated by devoting sufficient time for relaxation of the interface. The
adhesion in the relaxed interfaces was evaluated via the work of adhesion (Wadh).
Relaxation of the interface caused to decrease the atomic roughness of the PE
surface, which enhanced adhesion in all of the systems compared to their
unrelaxed models. In addition to surface flattening, relaxation also brought
about an increase in the atomic density at the interface, which led to enhance
the van der Waals interaction and increase interfacial adhesion.
PMID- 26422813
TI - We're all in this together: Midwifery student peer mentoring.
AB - Many higher education institutions have adopted mentoring programs for students
as a means of providing support, improve learning and enhance the student
experience. The aim of this project was to improve midwifery students experience
by offering a peer mentoring program to commencing students to assist with the
transition to university life and the rigours of the midwifery program. This
paper reports the evaluation of this specific mentoring program and the ongoing
development and implementation of a sustainable program within an Australian
University. A survey design was adopted to gather feedback from both mentees to
evaluate if the peer mentoring program enhanced the first year midwifery student
experience and ascertain how the program could be further developed. Fifty-five
students engaged with the peer mentors and completed the questionnaire regarding
the mentoring program. Specifically valuable was the positive impact that
mentoring had on midwifery student confidence, managing the demands of the
program and being motivated to keep going when the program requirements were
challenging. The success of this program rested largely with mentoring students
sharing their own experiences and providing reassurance that other students could
also succeed.
PMID- 26422814
TI - Development and validation of a tool for patient reporting of symptoms and signs
of the post-thrombotic syndrome.
AB - Post-thrombotic syndrome (PTS) is a long-term complication of deep-vein
thrombosis (DVT). The Villalta scale is the recommended tool for diagnosing PTS,
but requires a clinician's assessment in addition to patient self-assessment. In
the present study, we validated a self-administered tool for patient reporting of
leg symptoms and signs as a mean to assess PTS. We first validated a form for
patient self-reported Villalta (PRV1), then developed and validated a visually
assisted form (PRV2). The validity of PRV1 and PRV2 was assessed in patients
diagnosed with DVT between 2004 and 2012. Median time from DVT to inclusion was
5.1 and 3.5 years for PRV1 (n=162) and PRV2 (n=94), respectively. Patients were
requested to complete the PRV form before a scheduled visit. PTS diagnosed by the
original Villalta scale during the visit served as the reference method. PRV1
showed only moderate agreement for diagnosing PTS compared with the original
Villalta scale (kappa agreement 0.60, 95% CI 0.48-0.72), whereas PRV2 showed very
good agreement (0.82, 95% CI 0.71-0.94). In the validation of PRV2, PTS was
diagnosed in 54 (57%) patients according to the original Villalta scale and in 60
(64%) by PRV2. The sensitivity of PRV2 to detect PTS was 98% and the specificity
was 83%. We conclude that the visually assisted form for PRV is a valid and
sensitive tool for diagnosing PTS. Such a tool could be applied in further
clinical studies of PTS, making studies less resource demanding by reducing the
need for in-person clinic visits.
PMID- 26422815
TI - Flow dynamics in pediatric rigid bronchoscopes using computer-aided design
modeling software.
AB - OBJECTIVES/HYPOTHESIS: Observed complications during rigid bronchoscopy,
including hypercarbia and hypoxemia, prompted us to assess how well rigid
bronchoscopes serve as an airway device. We performed computer-aided design flow
analysis of pediatric rigid bronchoscopes to gain insight into flow dynamics.
STUDY DESIGN: We made accurate three-dimensional computer models of pediatric
rigid bronchoscopes and endotracheal tubes. SOLIDWORKS (Dassault Systemes, Velizy
Villacoublay, France) flow analysis software was used to analyze fluid dynamics
during pressure-controlled and volume-controlled ventilation. METHODS: Flow
analysis was performed on rigid bronchoscopes and similar outer diameter
endotracheal tubes comparing resistance, flow, and turbulence during two
ventilation modalities and in common surgical scenarios. RESULTS: Increased
turbulent flow was observed in bronchoscopes compared to more laminar flow in
endotracheal tubes of similar outer diameter. Flow analysis displayed higher
resistances in all pediatric bronchoscope sizes except one (3.0 bronchoscope)
compared to similar-sized endotracheal tubes. Loss of adequate ventilation was
observed if the bronchoscope was not assembled correctly or if increased peak
inspiratory pressures were needed. Anesthesia flow to the patient was reduced by
63% during telescope insertion. CONCLUSIONS: Flow analysis illustrates increased
turbulent flow and increased airflow resistance in all but one size of pediatric
bronchoscopes compared to endotracheal tubes. This increased turbulence and
resistance, along with the unanticipated gas distal exit pattern, may contribute
to the documented hypercarbia and hypoxemia during procedures. These findings may
explain why hypoxemia and hypercarbia are commonly observed during rigid
bronchoscopy, especially when positive pressure ventilation is needed. LEVEL OF
EVIDENCE: NA Laryngoscope, 126:1940-1945, 2016.
PMID- 26422816
TI - Copper-transporting ATPases: The evolutionarily conserved machineries for
balancing copper in living systems.
AB - Copper ATPases (Cu-ATPases) are ubiquitous transmembrane proteins using energy
from ATP to transport copper across different biological membranes of prokaryotic
and eukaryotic cells. As they belong to the P-ATPase family, Cu-ATPases contain a
characteristic catalytic domain with an evolutionarily conserved aspartate
residue phosphorylated by ATP to form a phosphoenzyme intermediate, as well as
transmembrane helices containing a cation-binding cysteine-proline
cysteine/histidine/serine (CPx) motif for catalytic activation and cation
translocation. In addition, most Cu-ATPases possess the N-terminal Cu-binding
CxxC motif required for regulation of enzyme activity. In cells, the Cu-ATPases
receive copper from soluble chaperones and maintain intracellular copper
homeostasis by efflux of copper from the cell or transport of the metal into the
intracellular compartments. In addition, copper pumps play an essential role in
cuproprotein biosynthesis by the uptake of copper into the cell or delivery of
the metal into the chloroplasts and thylakoid lumen or into the lumen of the
secretory pathway, where the metal ion is incorporated into copper-dependent
enzymes. In the recent years, significant progress has been made toward
understanding the function and regulation of Cu-transporting ATPases in archaea,
bacteria, yeast, humans, and plants, providing new insights into the specific
physiological roles of these essential proteins in various organisms and
revealing some conservative regulatory mechanisms of Cu-ATPase activity. In this
review, the structural, biochemical, and functional properties of Cu-ATPases from
phylogenetically different organisms are summarized and discussed, with
particular attention given to the recent insights into the molecular biology of
copper pumps in plants.
PMID- 26422817
TI - Association of Model for End-Stage Liver Disease Score and Mortality in Trauma
Patients With Chronic Liver Disease.
AB - IMPORTANCE: The Model for End-Stage Liver Disease (MELD) score is predictive of
trauma outcomes. OBJECTIVE: To determine whether a decrease in MELD score is
associated with improved mortality in critically ill trauma patients. DESIGN,
SETTING, AND PARTICIPANTS: We performed a retrospective registry study of
critically ill trauma patients 18 years or older with chronic liver disease
treated between August 3, 1998, and January 5, 2012, at 2 level I trauma centers
in Boston, Massachusetts. The consecutive sample included 525 patients (male, 373
[71.0%]; white, 399 [76.0%]; mean [SD] age, 55.0 [12.4] years). EXPOSURES: Change
in MELD score from intensive care unit (ICU) admission to 48 to 72 hours later.
MAIN OUTCOMES AND MEASURES: Thirty-day all-cause mortality. RESULTS: The mean
(SD) MELD score at ICU admission was 19.3 (9.7). The 30-day mortality was 21.9%.
The odds of 30-day mortality with a change in MELD score of less than -2, -2 to
1, +1 to +4, and greater than +4 were 0.23 (95% CI, 0.10-0.51), 0.30 (95% CI,
0.10-0.85), 0.57 (95% CI, 0.27-1.20), and 1.31 (95% CI, 0.58-2.96), respectively,
relative to a change in MELD score of 0 and adjusted for age, sex, race,
Charlson/Deyo Index, sepsis, number of acute organ failures, International
Classification of Diseases, Ninth Revision-based injury severity score, and ICU
admission MELD score. CONCLUSIONS AND RELEVANCE: A decrease in MELD score within
72 hours of ICU admission is associated with improved mortality.
PMID- 26422819
TI - On-chip supercapacitors with ultrahigh volumetric performance based on
electrochemically co-deposited CuO/polypyrrole nanosheet arrays.
AB - We introduce a new method for fabricating unique on-chip supercapacitors based on
CuO/polypyrrole core/shell nanosheet arrays by means of direct electrochemical co
deposition on interdigital-like electrodes. The prepared all-solid-state device
demonstrates exceptionally high specific capacitance of 1275.5 F cm(-3) (~40
times larger than that of CuO-only supercapacitors) and high-energy-density of
28.35 mWh cm(-3), which are both significantly greater than other solid-state
supercapacitors. More importantly, the device maintains approximately 100%
capacity retention at 2.5 A cm(-3) after 3000 cycles. The in situ co-deposition
of CuO/polypyrrole nanosheets on interdigital substrate enables effective charge
transport, electrode fabrication integrity, and device integration. Because of
their high energy, power density, and stable cycling stability, these newly
developed on-chip supercapacitors permit fast, reliable applications in portable
and miniaturized electronic devices.
PMID- 26422818
TI - Multifunctional Pristine Chemically Modified Graphene Films as Strong as
Stainless Steel.
AB - Pristine chemically modified graphene films with light weights and excellent
mechanical properties can be prepared by chemically engineering the structure of
the graphene oxide sheets and the microstructures of the films. Particularly,
these reduced graphene oxide films are as strong as stainless steel, ultra-tough,
and have high electrical and thermal conductivities.
PMID- 26422820
TI - Recombinational DNA repair is regulated by compartmentalization of DNA lesions at
the nuclear pore complex.
AB - The nuclear pore complex (NPC) is emerging as a center for recruitment of a class
of "difficult to repair" lesions such as double-strand breaks without a repair
template and eroded telomeres in telomerase-deficient cells. In addition to such
pathological situations, a recent study by Su and colleagues shows that also
physiological threats to genome integrity such as DNA secondary structure-forming
triplet repeat sequences relocalize to the NPC during DNA replication. Mutants
that fail to reposition the triplet repeat locus to the NPC cause repeat
instability. Here, we review the types of DNA lesions that relocalize to the NPC,
the putative mechanisms of relocalization, and the types of recombinational
repair that are stimulated by the NPC, and present a model for NPC-facilitated
repair.
PMID- 26422821
TI - A S-Layer Protein of Bacillus anthracis as a Building Block for Functional
Protein Arrays by In Vitro Self-Assembly.
AB - S-layer proteins create a cell-surface layer architecture in both bacteria and
archaea. Because S-layer proteins self-assemble into a native-like S-layer
crystalline structure in vitro, they are attractive building blocks in
nanotechnology. Here, the potential use of the S-layer protein EA1 from Bacillus
anthracis in constructing a functional nanostructure is investigated, and apply
this nanostructure in a proof-of-principle study for serological diagnosis of
anthrax. EA1 is genetically fused with methyl parathion hydrolase (MPH), to
degrade methyl parathion and provide a label for signal amplification. EA1 not
only serves as a nanocarrier, but also as a specific antigen to capture anthrax
specific antibodies. As results, purified EA1-MPH forms a single layer of
crystalline nanostructure through self-assembly. Our chimeric nanocatalyst
greatly improves enzymatic stability of MPH. When applied to the detection of
anthrax-specific antibodies in serum samples, the detection of our EA1-MPH
nanostructure is nearly 300 times more sensitive than that of the unassembled
complex. Together, it is shown that it is possible to build a functional and
highly sensitive nanosensor based on S-layer protein. In conclusion, our present
study should serve as a model for the development of other multifunctional
nanomaterials using S-layer proteins.
PMID- 26422822
TI - Disorder-specific versus transdiagnostic and clinician-guided versus self-guided
treatment for major depressive disorder and comorbid anxiety disorders: A
randomized controlled trial.
AB - Disorder-specific cognitive behavior therapy (DS-CBT) is effective at treating
major depressive disorder (MDD) while transdiagnostic CBT (TD-CBT) addresses both
principal and comorbid disorders by targeting underlying and common symptoms. The
relative benefits of these two models of therapy have not been determined.
Participants with MDD (n=290) were randomly allocated to receive an internet
delivered TD-CBT or DS-CBT intervention delivered in either clinician-guided (CG
CBT) or self-guided (SG-CBT) formats. Large reductions in symptoms of MDD
(Cohen's d>=1.44; avg. reduction>=45%) and moderate-to-large reductions in
symptoms of comorbid generalised anxiety disorder (Cohen's d>=1.08; avg.
reduction>=43%), social anxiety disorder (Cohen's d>=0.65; avg. reduction>=29%)
and panic disorder (Cohen's d>=0.45; avg. reduction>=31%) were found. No marked
or consistent differences were observed across the four conditions, highlighting
the efficacy of different forms of CBT at treating MDD and comorbid disorders.
PMID- 26422823
TI - Treatment of Hypercholesterolemia in 2015.
AB - Randomized, double-blind, placebo-controlled secondary prevention and primary
prevention studies and observational studies have documented that statins reduce
cardiovascular events in high-risk patients with hypercholesterolemia. The 2013
American College of Cardiology/American Heart Association guidelines on treatment
of hypercholesterolemia support the use of statins in 4 major groups that will be
discussed. The Expert Panel of these guidelines could find no data supporting the
routine use of nonstatin drugs combined with statins to further reduce
cardiovascular events. Since these guidelines were published, a double-blind
randomized trial of 18,144 patients with an acute coronary syndrome demonstrated
at a 7-year follow-up that the incidence of cardiovascular events was 34.7% in
patients randomized to simvastatin plus placebo versus 32.7% in patients
randomized to simvastatin plus ezetimibe (hazard ratio = 0.936; P = 0.016).
Proprotein convertase subtilisin/kexin type 9 inhibitors further lower serum low
density lipoprotein cholesterol by 50%-70% in patients treated with statins and 4
phase 3 trials including more than 70,000 patients are investigating whether
these monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 will
lower cardiovascular events.
PMID- 26422824
TI - Challenges of LADA Diagnosis and Treatment: Lessons From 2 Case Reports.
AB - Latent autoimmune diabetes in adults (LADA) is a subtype of autoimmune diabetes,
which shares characteristics of both Type 1 and 2 diabetes (T1D and T2D), and for
this reason, it is often confused with other types of diabetes, misdiagnosed, and
inappropriately treated. Two cases were presented (41-year-old and 50-year-old
females), one occasionally diagnosed during routine health checkup, the other one
identified as having T2D, and as far as misclassified and not optimally treated.
Now, after approximately 9 months of LADA diagnosis, the first patient has an
optimal metabolic control while maintaining the values of glycated hemoglobin to
around 7% with small doses of analogue insulin (lispro 4-6 UI) before meals and
long acting insulin (glargine 4-6 UI) at bedtime. The second patient, after
approximately 2 years from the LADA diagnosis, has an optimal metabolic control,
with maintenance of glycated hemoglobin to around 6.5%, and stable C-peptide
level (around 1.5 ng/mL), only with dietary and exercise habits. To avoid
misclassification, any patient who does not fit the typical T2D profile, or with
poor glycemic control, and who does not follow the expected clinical course, as
become insulin dependent sooner than expected, should be investigated to exclude
LADA. To define the best therapeutic approach, each patient must be evaluated and
therapy tailored on his/her specific profile, considering as very low insulin
doses may be effective to maintain a successful metabolic control and the only
dietary approach may be sufficient until the insulin-secretory capacity remains
good.
PMID- 26422825
TI - Economic analyses of stress urinary incontinence surgical procedures in women.
AB - INTRODUCTION: To evaluate the quality of economic analysis (EA) of surgical
procedures for stress urinary incontinence (SUI) in women. METHODS: A MEDLINE
search on EA for SUI surgical procedures for the years 2000-2014 included the
MeSH terms "tension-free vaginal tape," "TVT," "trans-obturator tape," "TOT,"
"Burch colposuspension" (BC), "stress urinary incontinence," "economic analysis,"
and "cost-effectiveness analysis." Important criteria for evaluating articles
were selected from panels that set out criteria to evaluate EA [Scales CD, Jr.,
Christopher SS, American Urological Association 32:121-128, 2013], [Hsieh MH,
Maxwell MV, J Urol 178 1867-1874, 2007], [Wu JM, Catherine CM, Conover MM, et
al., Obstet Gynecol 123 1201-1206, 2014]. RESULTS: Thirteen articles were
identified: TVT compared to BC (6), to other surgical procedures for SUI (1), to
TOT (3) and to the mini-sling (1); open BC compared to laparoscopic BC (1), and
analysis of various slings and meshes for various types of incontinence (1).
Articles originated from: United States (3), Europe (4), United Kingdom (4), and
Canada (2). Eight described cost-effectiveness analysis (CEA), two cost-utility
analysis, and three cost comparison. Follow-up time for patients ranged from 6 to
24 months in eight articles, with four having a minimum of 24 months follow-up.
Studies mostly adhered to the criteria, however indirect costs, sensitivity
analysis, and efficacy parameters varied. Long-term synthetic sling-related
complications were not included. CONCLUSION: Although CEA for SUI surgery is a
burgeoning field, study comparisons remain difficult due to some variability,
including health care delivery systems. As women live longer, long-term data will
become critical as complications and reoperations can affect the real cost of SUI
corrective procedures. Neurourol. Urodynam. 35:1040-1045, 2016. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26422826
TI - Activation of Prodrug Treosulfan at pH 7.4 and 37 degrees C Accompanied by
Hydrolysis of Its Active Epoxides: Kinetic Studies with Clinical Relevance.
AB - Treosulfan (TREO), originally registered for treatment of ovarian cancer, is
currently being investigated for conditioning prior to hematopoietic stem cell
transplantation. TREO is a prodrug, which undergoes a pH- and temperature
dependent two-step conversion to active monoepoxide [S,S-EBDM, (2S,3S)-1,2
epoxybutane-3,4-diol-4-methanesulfonate] and diepoxide [S,S-DEB, (2S,3S)-1,2:3,4
diepoxybutane]. In this paper, the kinetics of the nonenzymatic transformation of
TREO at pH 7.4 and 37 degrees C were studied for the first time including the
effects of the TREO concentration, buffer concentration, ionic strength, and the
presence of NaCl. Transformation of TREO was well described by a kinetic model,
which included first-order reactions for TREO activation, that is, TREO -> S,S
EBDM -> S,S-DEB, and pseudo-first-order reactions for the hydrolytic
decomposition of S,S-EBDM and S,S-DEB. In contrast to the two-step activation of
TREO, the hydrolysis of epoxides was influenced by electrolytes. In phosphate
buffered saline, decomposition of S,S-EBDM and S,S-DEB (mean half-lives 25.7 and
15.4 h) proceeded much slower than their formation (mean half-lives 1.5 and 3.5
h). In conclusion, the kinetics of the nonenzymatic transformation of TREO in the
presence of plasma electrolytes cannot contribute to the very low levels of S,S
EBDM and S,S-DEB observed in patient plasma. The results also indicate that
elimination of TREO proceeds primarily via conversion to S,S-EBDM.
PMID- 26422827
TI - Alterations in cellular metabolome after pharmacological inhibition of Notch in
glioblastoma cells.
AB - Notch signaling can promote tumorigenesis in the nervous system and plays
important roles in stem-like cancer cells. However, little is known about how
Notch inhibition might alter tumor metabolism, particularly in lesions arising in
the brain. The gamma-secretase inhibitor MRK003 was used to treat glioblastoma
neurospheres, and they were subdivided into sensitive and insensitive groups in
terms of canonical Notch target response. Global metabolomes were then examined
using proton magnetic resonance spectroscopy, and changes in intracellular
concentration of various metabolites identified which correlate with Notch
inhibition. Reductions in glutamate were verified by oxidation-based colorimetric
assays. Interestingly, the alkylating chemotherapeutic agent temozolomide, the
mTOR-inhibitor MLN0128, and the WNT inhibitor LGK974 did not reduce glutamate
levels, suggesting that changes to this metabolite might reflect specific
downstream effects of Notch blockade in gliomas rather than general sequelae of
tumor growth inhibition. Global and targeted expression analyses revealed that
multiple genes important in glutamate homeostasis, including glutaminase, are
dysregulated after Notch inhibition. Treatment with an allosteric inhibitor of
glutaminase, compound 968, could slow glioblastoma growth, and Notch inhibition
may act at least in part by regulating glutaminase and glutamate.
PMID- 26422828
TI - Reply: To PMID 25747677.
PMID- 26422829
TI - The Effects of Cataract Surgery on Patients With Wet Macular Degeneration.
PMID- 26422830
TI - Spectral-Domain Optical Coherence Tomography of Subretinal Hyperreflective
Exudation in Myopic Choroidal Neovascularization.
PMID- 26422832
TI - Epidural Cortical Stimulation as a Treatment for Poststroke Aphasia: A Systematic
Review of the Literature and Underlying Neurophysiological Mechanisms.
AB - BACKGROUND: Nearly 15 million people suffer from stroke every year worldwide,
with about 20% of the survivors retaining chronic aphasic symptoms. Spontaneous
recovery is limited to 3 to 6 months. Cortical stimulation techniques have been
proposed to enhance the recovery process. OBJECTIVE: The goal of this study was
to evaluate the benefit of epidural cortical stimulation for the treatment of
poststroke aphasia, based on a systematic review of the literature. METHODS: An
extensive PubMed search was performed for English language articles published
from 1990 to 2014 with the keywords (cortical OR epidural) AND stimulation AND
stroke AND (aphasia OR language OR speech). The criteria analyzed included the
type of study, epidemiology of patients, stroke, aphasia, stimulation protocol,
concurrent rehabilitation therapies, language evaluations, results observed, and
follow-up. RESULTS: Seven cases were reported to date (3 case reports, 1
randomized controlled trial). All patients experienced nonfluent aphasia
following an ischemic stroke. All four studies reported encouraging effects of
the stimulation with improved lexical access and fluency for all patients. The
effects were specific, independent of the motor recovery or of the pain reported
by the patients, and they were linked to the stimulation parameters. CONCLUSIONS:
Due to the small number of existing cases in the literature, the strength of the
evidence is still low. Two main hypotheses of neurobiological mechanisms have
been explored: either using continuous stimulation to modify cortical
perilesional inhibition or using intermittent stimulation during the speech and
language therapy sessions to explore synaptic plasticity and long-term
potentiation or depression. To establish the role of epidural stimulation and the
relevant stimulation protocols and parameters, large randomized controlled trials
are mandatory. We suggest avenues of investigation.
PMID- 26422831
TI - Reply: To PMID 26314663.
PMID- 26422834
TI - Distance education: Not for PAs, yet.
PMID- 26422833
TI - The role of MAGT1 in genetic syndromes.
AB - Disturbances in magnesium homeostasis, often linked to altered expression and/or
function of magnesium channels, have been implicated in a plethora of diseases.
This review focuses on magnesium transporter 1 (MAGT1), as recently described
changes in this gene have further extended our understanding of the role of
magnesium in human health and disease. The identification of genetic changes and
their functional consequences in patients with immunodeficiency revealed that
magnesium and MAGT1 are key molecular players for T cell-mediated immune
responses. This led to the description of XMEN (X-linked immunodeficiency with
magnesium defect, Epstein Barr Virus infection, and neoplasia) syndrome, for
which Mg2+ supplementation has been shown to be beneficial. Similarly, the
identification of a copy-number variation (CNV) leading to dysfunctional MAGT1 in
a family with atypical ATRX syndrome and skin abnormalities, suggested that the
MAGT1 defect could be responsible for the cutaneous problems. On the other hand,
recent genetic investigations question the previously proposed role for MAGT1 in
intellectual disability. Understanding the molecular basis of the involvement of
magnesium and its channels in human pathogenesis will improve opportunities for
Mg2+ therapies in the clinic.
PMID- 26422835
TI - Patient-derived orthotopic xenografts: better mimic of metastasis than
subcutaneous xenografts.
AB - The majority of human solid tumours do not metastasize when grown subcutaneously
in immunocompromised mice; this includes patient-derived xenograft (PDX) models.
However, orthotopic implantation of intact tumour tissue can lead to metastasis
that mimics that seen in patients. These patient-derived orthotopic xenograft
(PDOX) models have a long history and might better recapitulate human tumours
than PDX models.
PMID- 26422836
TI - Medical Devices; Cardiovascular Devices; Classification of the Steerable
Cardiac Ablation Catheter Remote Control System. Final order.
AB - The Food and Drug Administration (FDA) is classifying the steerable cardiac
ablation catheter remote control system into class II (special controls). The
special controls that will apply to the device are identified in this order and
will be part of the codified language for the steerable cardiac ablation catheter
remote control system's classification. The Agency is classifying the device into
class II (special controls) in order to provide a reasonable assurance of safety
and effectiveness of the device.
PMID- 26422837
TI - Preventing falls and fall-related injuries in health care facilities.
PMID- 26422839
TI - Equitable and inequitable healthcare.
PMID- 26422840
TI - The evaluation of transient hypothyroidism in patients diagnosed with congenital
hypothyroidism.
AB - BACKGROUND/AIM: Congenital hypothyroidism (CH) is divided into two groups as
'permanent' and 'transient' We aimed to determine the rate of transient and
permanent congenital hypothyroidism of the newborns referred to our clinic.
MATERIALS AND METHODS: Of the newborns who were referred to our clinic from the
neonatal screening program, those who were diagnosed with CH and started
treatment were included in the study. The treatments of the patients whose
required daily treatment dose was reduced to under 1 ug/kg were terminated and
those who were followed monthly and whose fT4 and thyroid-stimulating hormone
(TSH) levels were normal at least 3 times without treatment were considered to
have transient hypothyroidism. RESULTS: Of the 256 newborns referred to our
clinic from the neonatal screening program, 114 (44.5%) were diagnosed with CH.
Of the CH patients, 70% (n = 58) were evaluated to have permanent and 30% (n =
25) transient hypothyroidism. Neonatal and serum TSH levels and treatment doses
were found to be significantly lower in the transient hypothyroidism patients.
CONCLUSION: Initial measurements of the serum TSH level and the required doses of
L-thyroxine therapy for maintaining normal thyroid hormone levels, growth, and
development may have a predictive role for differentiating permanent forms of CH
from transient forms.
PMID- 26422838
TI - Italian guidelines for the use of antiretroviral agents and the diagnostic
clinical management of HIV-1 infected persons. Update December 2014.
PMID- 26422841
TI - Cardiac factors affecting the success of vardenafil in erectile dysfunction.
AB - BACKGROUND/AIM: To evaluate the predictability of vardenafil success in patients
with erectile dysfunction (ED) by using cardiological tests. MATERIALS AND
METHODS: Patients diagnosed with ED who did not benefit from lifestyle changes (n
= 68) were evaluated with an abridged 5-item version of the International Index
of Erectile Function (IIEF-5). The pretreatment and posttreatment IIEF-5 scores
were compared with pretreatment data obtained from cardiological examinations.
RESULTS: When pretreatment scores were compared with test parameters, mitral flow
E/A ratio and tissue Doppler imaging (TDI) E'/ A', exercise test duration,
exercise capacity in MET, and percentage of maximum heart rate were found to be
statistically significant. Furthermore, there was a significant negative
correlation between mitral flow E/A ratio, TDI E'/A', exercise test duration,
exercise capacity in MET, and the difference in post- and pretreatment IIEF-5
scores. CONCLUSION: As a diastolic function indicator, TDI E'/A' positively
correlates with pretreatment IIEF-5 scores and negatively correlates with the
beneficial effect of vardenafil treatment. As a result, the cardiological status
of the patient correlates with individual IIEF-5 scores, and it seems to be
useful in predicting vardenafil success.
PMID- 26422842
TI - Sexuality and sexual dysfunction in spinal cord-injured men in Turkey.
AB - BACKGROUND/AIM: To provide a comprehensive evaluation of sexual function and
dysfunction in spinal cord-injured men based on self-reports of patients.
MATERIALS AND METHODS: Forty-seven spinal cord-injured men who completed the
spinal shock and rehabilitation period were included. Patients were asked to
complete a questionnaire developed to assess social status, sexual activities,
abilities, and sexuality education after injury. Neurologic levels of patients
were classified according to American Spinal Cord Injury Association protocol.
Erectile function was evaluated by International Index of Erectile Function-5
(IIEF-5) questionnaire. RESULTS: Patients were aged between 20 and 62 years
(mean: 35.2). Twenty-eight patients had T10 and above, 15 between T11 and L2, and
4 cauda conus injury. While 61.7% of the patients declared sexual activity, 93.6%
declared some degree of erection. Mean IIEF-5 score was 5.3 and 87.3% of the
patients had moderate to severe erectile dysfunction. CONCLUSION: Continuation of
sexual activity after injury is very important and has a great impact on quality
of life and interpersonal relationships for spinal cord-injured men. More
attention must be given to sexuality after spinal cord injury. A very high rate
of sexual dysfunction in spinal cord-injured patients was found and the
importance of sexual education was emphasized in this study.
PMID- 26422843
TI - Esophageal replacement by hydroxylated bacterial cellulose patch in a rabbit
model.
AB - BACKGROUND/AIM: To repair esophageal defects by hydroxylated and kombucha
synthesized bacterial cellulose (HKBC) patch in a rabbit model. MATERIALS AND
METHODS: Semicircular esophageal defects 1 cm in length of the cervical esophagus
were initially created in 18 Japanese big-ear rabbits and then repaired with HKBC
patch grafts. The clinical outcomes including survival rate, weight change, food
intake, and hematological and radiologic evaluation were observed. After X-ray
evaluation, the rabbits were sacrificed sequentially at 1, 3, and 6 months for
histopathologic analysis with light microscopy and scanning electron microscopy.
RESULTS: Survival rate during the first month was 88.9% (n = 16). Two rabbits
died from anastomotic leakage during the entire follow-up. Postoperatively,
feeding function and body weight were gradually restored in the surviving
animals. No hematological abnormalities were found, and no obvious anastomotic
leakage, stenosis, or obstruction was observed under X-ray examination. The
histopathologic results showed a progressive regeneration of the esophagus in the
graft area, where the neo-esophagus tissue had characteristics similar to native
esophageal tissue after 3 months of surgery. CONCLUSION: HKBC is beneficial for
esophageal tissue regeneration and may be a promising material for esophageal
reconstruction.
PMID- 26422844
TI - Bilateral sympathicotomy for hyperhidrosis without using single-lung ventilation.
AB - BACKGROUND/AIM: The goal of this retrospective study was to evaluate the outcomes
and complications of bilateral videothoracoscopic sympathicotomy without using
single-lung ventilation in the treatment of primary hyperhidrosis and facial
blushing. MATERIALS AND METHODS: We retrospectively reviewed 154 consecutive
patients (70 females and 84 males) who underwent bilateral sympathicotomy for
palmar, axillary, and facial/scalp hyperhidrosis or facial blushing from February
2005 to June 2013. The patients were intubated with single-lumen endotracheal
tube, and then sympathicotomies were performed via videothoracoscopy during
controlled apnea periods. RESULTS: Sympathicotomies were performed at costal
levels 2, 3, and 4. No perioperative mortality or conversion to open surgery was
recorded. Mean operation time was 31.2 +/- 2.4 min and mean hospital stay was 1.1
+/- 0.6 days. One patient experienced a unilateral pneumothorax that required
treatment. There were no abnormal hemodynamic parameters measured during the
perioperative apnea periods. The long term follow-up period was 21.4 +/- 5
months. Twenty-nine cases (18.8%) were complicated by compensatory sweating. No
recurrence was observed during the follow-up period. CONCLUSION: Video-assisted
thoracoscopic sympathicotomy without lung isolation provides effective cure of
primary hyperhidrosis and facial blushing. This procedure can shorten the
operative time without any aberrant hemodynamic shifts.
PMID- 26422845
TI - Determining the health beliefs and breast cancer fear levels of women regarding
mammography.
AB - BACKGROUND/AIM: Women's fears and health beliefs impact their participation in
early breast cancer diagnosis approaches. This study was conducted to determine
the health beliefs and fear levels of women older than 50 regarding mammography.
MATERIALS AND METHODS: A cross-sectional study was conducted in Turkey. The study
cohort consisted of 300 women selected by cluster sampling who agreed to
participate in the study. A health belief model scale and breast cancer fear
scale were used in data collection. Descriptive statistics, t-test, chi-square
test, and correlation analysis were used in the data analysis. RESULTS:
Participants had an age average of 59.88 +/- 6.49 years, and 86.3% were
illiterate. Only 34.7% of women stated that they had had a mammogram in the past.
The women's average scores on the lower dimensions of the health belief model
scale were determined as follows: 6.52 +/- 2.81 for sensitivity perception, 18.49
+/- 5.22 for seriousness perception, 16.80 +/- 4.31 for health motivation
perception, 15.83 +/- 3.89 for mammography benefit perception, and 28.74 +/- 8.35
for mammography barrier perception. The score average of the breast cancer fear
scale was determined as 23.81 +/- 9.71. CONCLUSION: We observed that women's
health beliefs and breast cancer fear levels impacted their participation in
mammography.
PMID- 26422846
TI - Self-perception of quality of life in patients treated with antipsychotics.
AB - BACKGROUND/AIM: Despite extensive research, normal functionality remains
problematic in patients with schizophrenia. Issues such as quality of life,
subjective well-being, or psychosocial performance are currently objectives of
interest. There are limited data collected prospectively on patients' perception
of quality of life as compared between treatment groups, especially in developing
countries. The aim of the present study was to analyze the evolution of patients'
reported quality of life in patients with schizophrenia or related disorders
treated with antipsychotics, in naturalistic settings. MATERIALS AND METHODS: The
study was designed as a 12-month prospective observational study of 131 subjects
with schizophrenia or related disorders treated with haloperidol, olanzapine,
risperidone, quetiapine, or aripiprazole, recruited from consecutive hospitalized
patients in a psychiatry department. RESULTS: The mean scores for patients'
reported quality of life and its components and for satisfaction with treatment
had a favorable evolution, but increases were of reduced magnitude. The
differences among treatment groups were not statistically significant, with few
exceptions. A great variability of data was found. CONCLUSION: Studies with a
stratified analysis by factors influencing quality of life perceptions in this
category of patients might allow the identification of differences, if any,
between antipsychotics in this domain.
PMID- 26422847
TI - Multidrug resistance and integron carriage in clinical isolates of Pseudomonas
aeruginosa in Tehran, Iran.
AB - BACKGROUND/AIM: Pseudomonas aeruginosa is the cause of 10% of hospital-acquired
infections. The organisms are often multidrug- resistant, mediated mostly by
antibiotic-resistant integrons. The aim of this research was to study integron
carriage and its association with multidrug resistance in burn and nonburn
clinical isolates of P. aeruginosa. MATERIALS AND METHODS: A total of 112 P.
aeruginosa clinical isolates were collected from the Motahari and Shohadaye
Tajrish hospitals in Tehran between July and December 2011. Antibiotic
susceptibility to 13 antibiotics was determined by disk diffusion. Detection of
integron classes 1 and 2 and amplifications of internal variable regions (IVRs)
of class 1 integrons were carried out by PCR and specific primers. RESULTS: Among
the 112 isolates, 77 were from burn patients and 35 were nonburn isolates.
Multidrug resistance and class 1 integron carriage were both significantly higher
in the burn isolates compared to the nonburn strains (97.4% vs. 22.8% and 82.3%
vs. 17.7%, respectively). Class 2 integron (2.7%) was only present in the burn
isolates. Amplification of IVRs of class 1 integrons revealed 3 different
fragment arrays. CONCLUSION: The significant association between multidrug
resistance and integron carriage among P. aeruginosa burn isolates suggests a
dissemination of resistance determinants by horizontal gene transfer.
PMID- 26422848
TI - A study of the effect of Bacillus thuringiensis serotype H14 (subspecies
israelensis) delta endotoxin on Musca larva.
AB - BACKGROUND/AIM: House flies (Musca domestica) are of major public health concern
in areas with poor sanitation and hygiene conditions. Biological control through
the use of parasitoids and pathogens is one of the alternatives to the use of
chemical pesticides for control of insects of public health importance. MATERIALS
AND METHODS: The effects of the delta endotoxin of Bacillus thuringiensis on
house fly larval mortality were studied. Gel filtration and SDS-PAGE methods were
used for separation and purification of proteins. Delta endotoxin was incubated
with larvae in concentrations of 0.43 mg/mL and 0.27 mg/mL in bioassay tests.
RESULTS: The results of this study indicated protein crystal toxicity against
larvae of the house fly. A concentration of 0.43 mg/mL of this toxin caused 100%
mortality in house fly larvae. The LD50 amount of these toxins was calculated as
125 ug/g. CONCLUSION: The results of this study suggest that the use of the
protein crystal including delta endotoxin of Bacillus thuringiensis serotype H14
is an effective weapon in the biological fight against the house fly.
PMID- 26422850
TI - Effects of Turkish propolis on expression of hOGG-1 and NEIL-1.
AB - BACKGROUND/AIM: Propolis is a bee product with antioxidative, antimutagenic, and
other beneficial properties, and it is used as a natural drug. It is rich in
polyphenolic compounds. Its composition varies depending on the particular
geographical region. Oxidative stress is caused by an imbalanced free radical
production and antioxidant system. The effects of flavonoids on the expression of
DNA repair enzymes have been examined previously; however, no study has
investigated the effects of propolis. This study investigated the effects of
ethanolic extracts of Turkish propolis (EEP) on the expression of DNA repair
enzymes. MATERIALS AND METHODS: The effects of EEP and tertiary-butyl
hydroperoxide (t-BHP) on cell viability were determined using MTT DNA damage was
determined using comet assay. mRNA expression of target enzymes was detected
using RT-PCR. RESULTS: According to the cytotoxicity analysis, after a recovery
time of 4 h, appropriate damage agent t-BHP and optimum EEP concentrations were
300 uM and 200 ug/mL, respectively. 8-Oxoguanine-glycosylase (hOGG-1) and
endonuclease-VIII-like-1 (NEIL-1) expressions increased in the positive control
group (t-BHP alone) and the study group (t-BHP+EEP). Maximum increase in NEIL-I
expression was at hour 12 in the positive control group and at hour 8 in the
study group. CONCLUSION: EEP can be considered as a potential source of
functional food and pharmaceutical agents.
PMID- 26422849
TI - Is there a role of interstitial cells of Cajal and mast cells and eosinophils in
appendicitis in children?
AB - BACKGROUND/AIM: The aim of this study was to compare the distribution of
interstitial Cajal cells, eosinophils, and mast cells in normal and inflamed
appendices, and to evaluate the correlation of presence of these cells with
severity of inflammation in appendicitis. MATERIALS AND METHODS: The appendicitis
group (n = 30) was divided further into three groups according to the macroscopic
description and the histological findings. Ten normal appendices served as
controls. Tissue samples were processed for routine histological examination.
Additionally, all sections were immunohistochemically stained with CD117 and mast
cell tryptase antibodies. RESULTS: When specimens were compared in terms of Cajal
cells, the observed mean number for the appendicitis group was 4.9 and for the
control group it was 8.3. In contrast, eosinophils and mast cells were
significantly increased in the appendicitis group when compared with the control
group. CONCLUSION: We detected that eosinophils and mast cells are increased in
appendicitis, and correlate with the degree of inflammation of the appendix. The
density of interstitial Cajal cells was significantly lower in patients with
severe appendix inflammation compared to controls. The histopathological
differences observed in this study may help elucidate the pathophysiology of
appendicitis.
PMID- 26422851
TI - The effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX
4016) on mice models of endotoxic and septic shock.
AB - BACKGROUND/AIM: Nitric oxide-donating nonsteroidal antiinflammatory drugs (NO
NSAIDs) are a promising new class of antiinflammatory agents, which are obtained
by adding NO-donating moieties to the existing conventional NSAID molecules. The
aim of this study was to investigate the effects of aspirin, flurbiprofen, and NO
donating acetylsalicylic acid (NCX 4016) on cecal ligation and puncture (CLP) and
endotoxin-induced septic shock (LPS) models in mice. MATERIALS AND METHODS:
Overall survival and spleen and liver weights were monitored in LPS and CLP
models. Histopathological examinations of liver and spleen were performed at the
end of the experimental protocols. RESULTS: NCX 4016 was able to reverse the
increased spleen weight in CLP-operated animals, whereas aspirin or flurbiprofen
did not. Similar to the results of the CLP model, none of the drugs modified the
survival rates in the LPS model. Flurbiprofen in particular produced significant
histopathological damage in spleens and livers, which was less significant with
aspirin. NCX 4016 did not cause any liver damage. CONCLUSION: NCX 4016 has the
potential to be used in septic states, while special attention has to be paid to
the effects of aspirin and flurbiprofen on the liver and spleen.
PMID- 26422852
TI - Epidemiology, causative agents, and risk factors affecting human otomycosis
infections.
AB - BACKGROUND/AIM: Otomycosis, or fungal otitis externa, has typically been
described as fungal infection of the external auditory canal, with infrequent
complications involving the middle ear. This study assessed a mycological
analysis of fungal debris from externalauditory canals of patients at Tanta
University Hospital, Gharbia Governorate, Egypt. MATERIALS AND METHODS: The
samples were collected over a year from the 110 patients that were clinically
diagnosed to have otomycosis. The samples were then inoculated and culture plates
were examined for the presence of fungal growth. RESULTS: The results showed that
Aspergillus niger was the most common fungus causing otomycosis. It was more
common among males aged 21-40 years. The incidence was higher in the summer and
spring seasons. Manual workers and students had the highest frequency based on
occupational incidence. The most common presenting complaint was itching. Trauma
to the external auditory canal was the most common predisposing factor.
CONCLUSION: The epidemiological profile of otomycosis infection varied according
to different factors in the study population.
PMID- 26422853
TI - The effect of swimming and type of stroke on bone metabolism in competitive
adolescent swimmers: a pilot study.
AB - BACKGROUND/AIM: Physical activity plays a key role in increasing and preserving
bone mineral density (BMD). Effects on bone development associated with various
nonweight-bearing sporting activities, such as swimming, are controversial.
Different strokes used in swimming may also present as another factor. The aim of
this study was to evaluate the effect of swimming and type of stroke on BMD in
competitive adolescent athletes. MATERIALS AND METHODS: Seventy-nine swimmers
between the ages of 10 and 21 years participated in this study. BMD was measured
with dual-energy X-ray absorptiometry at the lumbar vertebrae and left proximal
femur. Daily calorie intake and calcium consumption, and measurements of calcium,
phosphorus, alkaline phosphates, 25-hydroxyvitamin D (25(OH) D), and osteocalcin
were evaluated. RESULTS: Preliminary results revealed that the type of stroke had
no effect on BMD (P = 0.79). Additionally competitive swimmers did not have
augmented bone mineral accretion, and in 13.9% of athletes low BMD was confirmed.
Sixty percent of swimmers had either deficient or insufficient 25(OH) D levels
and a low mean calorie (P = 0.542) and calcium (P = 0.038) intake was observed.
CONCLUSION: This was the first study to evaluate the effect of swimming stroke on
BMD. Although no effect was statistically shown, further studies with a larger
series may determine this effect.
PMID- 26422854
TI - Vitamin and mineral deficiency in children newly diagnosed with celiac disease.
AB - BACKGROUND/AIM: To establish the frequency of vitamin and mineral deficiency in
children newly diagnosed with celiac disease. MATERIALS AND METHODS: The files of
patients diagnosed with celiac disease in our Pediatric Gastroenterology Clinic
from June 2008 to June 2013 were reviewed retrospectively. RESULTS: A total of 52
pediatric patients diagnosed with celiac disease via serology and duodenal biopsy
and who fulfilled the study criteria were enrolled in the study. The mean
diagnosis age of the patients was 8.5 +/- 3.9 years and 33 (63.5%) of the
patients were female. Vitamin D, vitamin A, vitamin E, zinc, and iron
deficiencies were determined in 27 (51.9%), 4 (7.7%), 7 (13.5%), 35 (67.3%), and
18 (34.6%) patients, respectively, at the time of diagnosis. Vitamin D deficiency
was observed more frequently in patients with growth retardation at the time of
application (P = 0.02). CONCLUSION: Vitamin D, zinc, and iron deficiency are
frequently observed in pediatric patients with celiac disease at the time of
diagnosis. Therefore, serum vitamin D, zinc, and iron levels should be checked in
all children diagnosed with celiac disease.
PMID- 26422855
TI - A case-control study: evaluation of vitamin D metabolism in patients with
vitiligo.
AB - BACKGROUND/AIM: Reduced vitamin D is considered as one of the environmental
factors that can increase the prevalence of certain autoimmune diseases. This
study aimed to assess vitamin D metabolism in patients with vitiligo. MATERIALS
AND METHODS: A prospective case-control study was conducted on 44 consecutive
patients with vitiligo vulgaris and 43 healthy controls. Their plasma 25
hydroxyvitamin D (25(OH)D), parathormone (PTH), calcium, magnesium, and phosphate
levels were measured. RESULTS: There was no significant difference in the mean
age, sex and Fitzpatrick skin phototype between the patient and control groups (P
> 0.05). The plasma levels of 25(OH)D and calcium were significantly decreased (P
= 0.002, P < 0.0001, respectively) and PTH and magnesium levels were
significantly increased in patients with vitiligo (P < 0.0001, P < 0.0001,
respectively). The advancement of age (P = 0.03, R = -0.18) and comorbid
autoimmune illnesses (P = 0.04) were found to be significantly associated with
lower 25(OH)D levels. CONCLUSION: There is a universal lack of 25(OH)D in the
Turkish population. Screening for vitamin D may be a tool for the presence of
comorbid autoimmune diseases. Further studies are needed to understand the role
of vitamin D metabolism in the pathogenesis of vitiligo.
PMID- 26422856
TI - Effects of melatonin and theanine administration on pentylenetetrazole-induced
seizures and brain tissue oxidative damage in ovariectomized rats.
AB - BACKGROUND/AIM: The effects of coadministration of melatonin and theanine
(Mel/Thea) on pentylenetetrazole (PTZ)-induced seizures and brain tissue
oxidative damage were investigated in ovariectomized (OVX) and sham-operated
rats. MATERIALS AND METHODS: The rats were divided into the following groups: 1)
sham, 2) ovariectomized (OVX), 3) sham-PTZ, 4) OVX- PTZ, 5) sham-Mel/Thea-PTZ,
and 6) OVX-Mel/Thea-PTZ. Groups 1-4 received saline, while groups 5 and 6
received a combination of Mel/Thea for 6 weeks. All animals except for those in
groups 1 and 2 received a single injection of PTZ. RESULTS: The OVX-PTZ group had
higher generalized tonic-clonic seizure (GTCS) latency compared to the sham-PTZ
group. Administration of Mel/Thea increased minimal clonic seizure and GTCS
latencies in both the sham-Mel/Thea-PTZ and OVX-Mel/Thea-PTZ groups compared to
the controls. Additionally, PTZ exposure increased malondialdehyde levels and
reduced thiol concentrations in brain tissues of both the sham-PTZ and OVX-PTZ
groups. Mel/Thea pretreatment resulted in MDA reduction and thiol increase in
brain tissues. CONCLUSION: The results of this study demonstrated the antioxidant
and anticonvulsant activities of Mel/Thea despite the presence or absence of
ovarian hormones.
PMID- 26422857
TI - Evaluation of GCF MMP-1, MMP-8, TGF-beta1, PDGF-AB, and VEGF levels in
periodontally healthy smokers.
AB - BACKGROUND/AIM: The effect of smoking on inflammatory biomarkers in gingival
crevicular fluid (GCF) is well established in the presence of periodontal
inflammation. However, it is not clear if smoking has an influence on matrix
metalloproteinase (MMP) and growth factor levels in the GCF of periodontally
healthy subjects. The aim of this study was to investigate GCF levels of MMP-1,
MMP-8, transforming growth factor (TGF)-beta1, platelet-derived growth factor
(PDGF)-AB, and vascular endothelial growth factor (VEGF) in smoking versus
nonsmoking periodontally healthy subjects. MATERIALS AND METHODS: Thirty-two
periodontally healthy subjects were included in this study. Probing depths,
bleeding on probing, and plaque index was assessed. GCF levels of MMP-1, MMP-8,
TGF-beta1, PDGF-AB, and VEGF were analyzed by enzyme-linked immunosorbent assay.
RESULTS: No significant differences were observed in the distribution of
demographic data between study groups. GCF total amount of PDGF-AB was
significantly lower in smokers compared to nonsmokers (P = 0.014). Total amount
of GCF MMP-1, MMP-8, TGF-beta1, and VEGF levels were similar in both study groups
(P = 0.022). CONCLUSION: Smoking has the effect of decreasing GCF PDGF-AB while
it does not affect GCF MMP-1, MMP-8, TGF-beta1, and VEGF in periodontally healthy
subjects. Since increased levels of these molecules are involved in periodontal
breakdown, our findings may emphasize the importance for maintenance of
periodontal health in smokers.
PMID- 26422858
TI - Hepatoprotective and antioxidant effects of lycopene in acute cholestasis.
AB - BACKGROUND/AIM: Lycopene, which is suggested to be a potent antioxidant, may play
a protective role in diseases related to oxidative stress. In order to understand
the effects of lycopene in the pathogenesis of cholestasis, we investigated the
effects of lycopene on oxidative stress parameters and DNA damage induced by
experimental biliary obstruction in the liver tissues and the lymphocytes of
Wistar albino rats. MATERIALS AND METHODS: The animals were randomized into 3
groups. The sham group was subjected to a sham operation, the BDL group was
subjected to bile duct ligation (BDL), and the BDL+L group was subjected to BDL
and treated with 10 mg/kg body weight of lycopene. After 7 days of treatment, the
liver functions, oxidative stress parameters, and DNA damage were evaluated.
RESULTS: The lycopene treatment significantly ameliorated the liver function
parameters in BDL rats. It significantly reduced malondialdehyde and nitric oxide
levels and enhanced reduced glutathione levels and catalase, superoxide
dismutase, and glutathione S transferase activities in the BDL rats. The lycopene
treatment also decreased DNA damage as assessed by comet assay in the lymphocytes
and hepatocytes of the BDL rats. CONCLUSION: These results suggest that lycopene
might have protective effects on acute cholestasis.
PMID- 26422859
TI - Determination-of apoptosis and cell cycle modulators (p16, p21, p27, p53, BCL-2,
Bax, BCL-xL, and cyclin D1) in thyroid follicular carcinoma, follicular adenoma,
and adenomatous nodules via a tissue microarray method.
AB - BACKGROUND/AIM: To identify the role of gene products associated with apoptosis
and cell cycle in the pathogenesis of thyroid follicular neoplasm. MATERIALS AND
METHODS: Thirty follicular adenomas (FAs), 16 follicular carcinomas (FCs), and 20
adenomatous nodules (ANs) were investigated with immunohistochemical staining of
p16, p21, p27, p53, Bcl-2, Bax, Bcl-xL, and cyclin D1 via a tissue microarray
method. RESULTS: Bcl-2 showed a significant difference between the benign groups
(AN and FA) and the malignant group (FC). Bax was significantly higher in the FC
group. p53 was lowest in the AN group and highest in the FC group with
significant differences between the groups. p16 was significantly higher in the
FC group than in the other groups. There was a significant difference between the
AN group and neoplastic lesions in terms of p21 staining. The number of cases
with positive p27 was lower in the AN group than the neoplastic groups. There was
no significant difference in terms of Bcl-xL and cyclin D1. CONCLUSION: Cell
cycle modulators, led by the Bcl-2 family, played an important role in the
pathogenesis of thyroid follicular neoplasm, and p53, p16, and p21 in particular
played a role in the carcinogenesis of FC.
PMID- 26422860
TI - The risk of tumor cell dissemination in mediastinoscopy: a cytological study.
AB - BACKGROUND/AIM: Mediastinoscopy is an invasive procedure that is used in the
diagnosis of mediastinal diseases and in staging lung cancer. Tumor cell seeding
during mediastinoscopy along the mediastinum and the incision line is a very rare
complication. This study aimed to test the safety of mediastinoscopy in terms of
tumor seeding by cytological evaluation of mediastinal lavage samples taken
before and after biopsy. MATERIALS AND METHODS: The patients who underwent
mediastinoscopy in our hospital between 2011 and 2014 were studied prospectively.
Seventy-three patients with a diagnosis of lung or mediastinal malignancy were
included in the study. All patients underwent classical cervical mediastinoscopy
and mediastinal lavages were taken before and after the biopsy. Both lavage
samples were sent to the pathology department in syringes for malignant cell
cytology screening. RESULTS: The results of the histopathological examinations of
lymph node biopsies were reactive in 25 patients and positive for malignancy in
48 patients. In 2 of 48 patients whose lymph nodes were reported to be positive
for malignancy, the mediastinal lavage sample was reported to be positive for
malignancy after biopsy, although it was negative preoperatively. In two
patients, both the pre- and postbiopsy lavage samples were reported to be
positive for malignancy. CONCLUSION: While performing dissection and biopsy
during mediastinoscopy, tumor seeding into the mediastinum may occur. Long follow
up periods and large patient series are needed to determine how cytopathological
examination of both fluids would affect the prognosis.
PMID- 26422861
TI - Does Atraucan cause more postdural puncture backache?
AB - BACKGROUND/AIM: Postdural puncture backache (PDPB) is the most frequent complaint
after spinal anesthesia. In the literature its importance is generally
overshadowed by postdural puncture headache. We studied two different kinds of
spinal anesthesia needles to compare their technical handling capacities and
incidences of PDPB. MATERIALS AND METHODS: Data of 256 pregnant female patients
undergoing cesarean delivery under spinal anesthesia were collected for the
study. Patients were divided into two groups as Group A (n = 109) and Group Q (n
= 147) according to the spinal needle used for spinal anesthesia (i.e. 26-gauge
atraumatic and 26-gauge Quincke needles, respectively). Backache incidences
during a 1-week period postoperatively and handling characteristics of the
needles were noted. RESULTS: Spinal anesthesia was successfully performed at one
attempt in 92.7% and 86.4% of patients in Groups A and Q, respectively. PDPB was
encountered in 62.4% and 44.2% of patients in Groups A and Q, respectively, and
the difference was statistically significant (P = 0.037). CONCLUSION: Both 26
gauge Atraucan and Quincke needles have excellent handling characteristics. PDPB
seems to be less common with the 26-gauge Quincke needle than with the Atraucan
needle.
PMID- 26422862
TI - Acute tuberculosis in the intensive care unit.
AB - BACKGROUND/AIM: The aim of this study was to determine mortality rates and to
evaluate clinical features of patients with active tuberculosis (TB) requiring
intensive care unit (ICU) admission. MATERIALS AND METHODS: The medical records
of active TB patients requiring ICU admission were retrospectively reviewed over
a 5-year period. RESULTS: Sixteen patients with active TB admitted to the ICU
were included in the study. Seven (43.8%) patients died in the ICU The cause of
mortality was septic shock in 5 patients and respiratory failure in 2 patients.
The Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential
Organ Failure Assessment (SOFA) scores were higher in patients who died (P =
0.012 and 0.048, respectively). Six of the 8 immunosuppressed patients and 1 of
the 8 nonimmunosuppressed patients died (P = 0.041). The median mechanical
ventilation (MV) duration was longer in patients who died (11 (5-45) days) than
in patients who survived (4.5 (3-7) days) (P = 0.036). Seven of the 8 patients
with nosocomial infection and/or coinfection died, while all of the patients
without additional infection survived (P = 0.01). CONCLUSION: Active TB patients
admitted to the ICU had higher mortality rates, especially patients with
immunosuppression, nosocomial infection, high APACHE II and SOFA scores, and
patients receiving MV.
PMID- 26422863
TI - Healthy subjects' knowledge of surgical complications: a hospital-based survey.
AB - BACKGROUND/AIM: There is an ongoing debate about how much a patient should know
about serious or frequently occurring risks of their surgery. In this study, we
evaluated healthy subjects' perspectives on knowledge of serious surgical
complications. MATERIALS AND METHODS: Three hundred and thirty healthy subjects
(151 women, 179 men; mean age: 43.6 +/- 17.3 years) were surveyed with the study
questionnaire. Social profile, surgical history of the healthy subjects, and
presence of a relative while giving preoperative consent were assessed. RESULTS:
Only 23.5% (39/166) of the subjects were informed about all the potential
complications of their previous surgical operation and 44.9% (73/166) did not get
any preoperative consent on surgical complications. A statistically significant
percentage of subjects who did not get proper information about the serious
complications involved in their surgery indicated a desire for preoperative
informed consent (97.0%, 128/132, P = 0.0001). CONCLUSION: The results indicated
that a significant percentage of the subjects wanted to be informed of the
potential complications of a surgery in the presence of a relative (73.9%,
192/260, P = 0.009). Involving a relative in preoperative consent may have a
positive effect on the patient and can increase the level of postoperative recall
of the risks.
PMID- 26422864
TI - Smoking cessation and the effect of nicotine dependence on relapse rate in Izmir,
Turkey.
AB - BACKGROUND/AIM: Smoking is the leading preventable cause of death in the world.
There is growing evidence of the need for community- based programs on smoking
cessation. The main purpose of this study is to establish the rate of smoking
cessation and restarting in 1 year at the Balcova Smoking Cessation Center.
MATERIALS AND METHODS: This is a prospective study with a study group of 359
individuals who quit smoking at the Balcova Smoking Cessation Center for at least
4 weeks between October 2009 and April 2010. The outcomes of the study were 1
year cessation rate and relapse rate. Individuals who reported restarting and/or
had CO measurements above 6 ppm were accepted as quitters who had relapsed.
RESULTS: The 1-year rate of smoking cessation was 30.1% for the study group. Of
the subjects who quit smoking, 50.1% started smoking again during the 1-year
follow-up. Relapse rate was also higher in nicotine addicts. Pharmacological
treatment was associated with increased success rates in smoking cessation.
CONCLUSION: Nicotine dependency was shown to be associated with lower rates of
smoking cessation and higher rates of relapse. Therefore, it is important to
begin smoking cessation attempts before individuals become serious addicts.
PMID- 26422865
TI - Epidemiological and clinical characteristics and management of oropharyngeal
tularemia outbreak.
AB - BACKGROUND/AIM: The purpose of this study was to determine the epidemiological
and clinical characteristics of patients diagnosed with tularemia and the
effectiveness of the administered treatments. MATERIALS AND METHODS: Patients
treated in our hospital between January 2009 and March 2011 and diagnosed with
tularemia were evaluated retrospectively. Patients' epidemiological and clinical
characteristics, administered treatments, and posttreatment findings were
recorded on patient monitoring forms. RESULTS: At anamnesis, 29% of patients used
water from wells and 71% used water from the network supply; moreover, 48.4% had
a history of contact with animals and 87.1% a history of lethargy. At physical
examination, 96.8% had a mass in the neck and 90.3% had fever. Gentamycin +
doxycycline therapy was administered to 45.2% of patients, while levofloxacin,
gentamycin, and streptomycin were used for the other patients. After treatment,
neck masses persisted in 48.4% of patients and complaints of lethargy and fever
in 6.5%. Treatment of these patients was initiated once tularemia had been
diagnosed, as test results were announced about 3 weeks later. Lymphadenopathy
excision was performed on 19.4% of patients in whom neck mass persisted.
CONCLUSION: Appropriate empiric antibiotherapy should be commenced in patients
presenting with neck mass, fever, and lethargy in regions with tularemia
epidemics.
PMID- 26422866
TI - Prevalence of hypertension and its association with obesity among school children
aged 6-15 living in Sakarya Province in Turkey.
AB - BACKGROUND/AIM: Childhood hypertension and its association with obesity are
becoming important issues worldwide. The prevalence of hypertension and obesity
are growing in both developed and developing countries. This paper aimed to
determine the prevalence of hypertension among school-aged children in Sakarya
(western part of Turkey) and to determine whether or not obesity is associated
with hypertension. MATERIALS AND METHODS: Twelve schools were randomly selected
from an area in the center of the Sakarya. A total of 2166 students participated
in the study. The students were visited at school, and their weights, heights,
and blood pressures were measured. The World Health Organization references were
used to determine the prevalence of overweightness, obesity, and hypertension.
RESULTS: The prevalences of hypertension and obesity were 15.1% (n = 326) and
18.0% (n = 390), respectively. Overweightness, obesity included, was found to be
present in 26.3% of the children. Sex and obesity were found to be associated
with hypertension; nevertheless, a positive family history of hypertension was
not associated with hypertension in children. CONCLUSION: The prevalence of
obesity and hypertension are high among school children of 6-15 years of age in
Sakarya. Obesity is associated with hypertension. Blood pressure measurements
should be part of routine clinical examination, especially in obese children.
PMID- 26422867
TI - VKORC1 and CYP2C9 genotypic data-based dose prediction alone does not accurately
predict warfarin dose requirements in some Malaysian patients.
AB - BACKGROUND/AIM: VKORC1 and CYP2C9 genetic polymorphisms may not accurately
predict warfarin dose requirements. We evaluated an existing warfarin dosing
algorithm developed for Malaysian patients that was based only on VKORC1 and
CYP2C9 genes. MATERIALS AND METHODS: Five Malay patients receiving warfarin
maintenance therapy were investigated for their CYP2C9*2, CYP2C9*3, and VKORC1
1639G>A genotypes and their vitamin K-dependent (VKD) clotting factor activities.
The records of their daily warfarin doses and international normalized ratio
(INR) 2 years prior to and after the measurement of VKD clotting factors
activities were acquired. The mean warfarin doses were compared with predicted
warfarin doses calculated from a genotypic-based dosing model developed for
Asians. RESULTS: A patient with the VKORC1-1639 GA genotype, who was supposed to
have higher dose requirements, had a lower mean warfarin dose similar to those
having the VKORC1-1639 AA genotype. This discrepancy may be due to the
coadministration of celecoxib, which has the potential to decrease warfarins
metabolism. Not all patients' predicted mean warfarin doses based on a previously
developed dosing algorithm for Asians were similar to the actual mean warfarin
dose, with the worst predicted dose being 54.34% higher than the required
warfarin dose. CONCLUSION: Multiple clinical factors can significantly change the
actual required dose from the predicted dose from time to time. The additions of
other dynamic variables, especially INR, VKD clotting factors, and concomitant
drug use, into the dosing model are important in order to improve its accuracy.
PMID- 26422868
TI - Antibiofilm activity of trans-cinnamaldehyde, p-coumaric, and ferulic acids on
uropathogenic Escherichia coli.
AB - BACKGROUND/AIM: Biofilm on urinary catheters results in persistent infections
that are resistant to antibiotics. In this study, phytochemicals were assessed as
alternative antimicrobials in preventing and inactivating E. coli biofilm on
urinary catheters. MATERIALS AND METHODS: Biofilm prevention was tested using
catheter fragments inoculated with E. coli and treated with trans-
cinnamaldehyde, p-coumaric, and ferulic acids (0%, 0.1%, 0.25%, and 0.5%) for 0,
1, 3, and 5 days. Inactivation of E. coli biofilm with the same agents at
concentrations of 0%, 1%, 1.25%, or 1.5% used for 0, 1, 3, or 5 days was also
evaluated. RESULTS: All used concentrations of trans-cinnamaldehyde prevented and
effectively inactivated E. coli biofilm formed on urinary catheter fragments. p
Coumaric (0.25% and 0.5%) and ferulic acids (0.5%) had preventive action on E.
coli biofilm formation in urinary catheter fragments. The number of uropathogenic
E. coli cells in biofilm formed in the lumen of a urinary catheter was
significantly reduced in the presence of p-coumaric and ferulic acids, but
complete inactivation of the biofilm formed was not observed, as opposed to the
use of trans-cinnamaldehyde. CONCLUSION: The obtained results indicate that
phytochemicals maybe an important source of antibiofilm agents that have
preventive action on E. coli biofilm formation on urinary catheters.
PMID- 26422869
TI - Periocular changes in topical bimatoprost and latanoprost use.
AB - BACKGROUND/AIM: To evaluate the periocular changes due to topical bimatoprost and
latanoprost use and to investigate their effects on the lacrimal drainage system.
MATERIALS AND METHODS: All participants (69 eyes of 43 patients, 52 eyes of 26
controls) were classified into three groups: bimatoprost (0.03%) users,
latanoprost (0.005%) users, and healthy controls. Each patient was examined
before prostaglandin therapy, and then at the first, third, sixth, and twelfth
month of therapy. Palpebral fissure height, upper eyelid crease, and levator
function were measured, and lacrimal system drainage irrigation was performed.
Periocular hyperpigmentation and upper eyelid sulcus were also examined. RESULTS:
No significant change was identified in palpebral fissure height or levator
function in any group. However, in upper eyelid crease, among bimatoprost users,
a statistically significant increase was observed when compared to the control
group (P < 0.001). Patients with skin type II and III, in bimatoprost users, and
patients with skin type III, in latanoprost users, had statistically significant
hyperpigmentation (P < 0.001) after the third month of therapy. During follow-up,
no lacrimal drainage system obstruction was seen. CONCLUSION: Topical bimatoprost
therapy causes more periocular changes than latanoprost therapy. Thus, in
unilateral cases, patients should be well informed about these probable changes
before therapy.
PMID- 26422870
TI - Urinary incontinence among women registered with a family health center in the
Southeastern Anatolia Region and the factors affecting its prevalence.
AB - BACKGROUND/AIM: In regions such as Sanliurfa, Turkey, where the fertility rate is
high, suitable health policies to easily and successfully treat urinary
incontinence (UI) are needed. This study was conducted to determine the
prevalence and risk factors for UI among women in the region. MATERIALS AND
METHODS: The participants in this cross-sectional study were selected by using 30
cluster sampling methods. A total of 300 women in the age group of 15-49 years
were contacted to participate. RESULTS: The prevalence of UI was 39.3% among
women in this sample but only 8.0% actually received treatment. The logistic
regression analysis showed that UI risk is increased 1.8 times by chronic
diseases, 2.7 times by menopause, 3.4 times by uterine prolapse, and 9.12 times
by cystocele. CONCLUSION: UI is a common health problem among the women in the
study region; however, these women do not actively seek treatment for this
problem.
PMID- 26422871
TI - Prevalence of Helicobacter pylori cagA, babA2, and dupA genotypes and correlation
with clinical outcome in Malaysian patients with dyspepsia.
AB - BACKGROUND/AIM: The severity of disease outcome in dyspepsia has been attributed
to Helicobacter pylori virulence genes. The aim of this study was to determine
the distribution of H. pylori virulence genes (cagA, babA2, and dupA) and to
determine whether or not there arises a significant correlation with clinical
dyspepsia outcomes. MATERIALS AND METHODS: H. pylori genotypes cagA, babA2, and
dupA were identified by polymerase chain reactions from gastric biopsy samples in
105 H. pylori-positive patients. RESULTS: The positive rates for cagA, babA2, and
dupA genes in H. pylori dyspeptic patients were 69.5%, 41.0%, and 22.9%,
respectivel cagA was more prevalent in Indians (39.7%), babA2 was more prevalent
in Malays (39.5%), and dupA detection occurred more frequently in both Indians
and Malays and at the same rate (37.5%). The Chinese inhabitants had the lowest
prevalence of the three genes. Nonulcer disease patients had a significantly
higher distribution of cagA (76.7%), babA2 (74.4%), and dupA (75.0%). There was
no apparent association between these virulence genes and the clinical outcomes.
CONCLUSION: The lower prevalence of these genes and variations among different
ethnicities implies that the strains are geographically and ethnically dependent.
None of the virulence genes were knowingly beneficial in predicting the clinical
outcome of H. pylori infection in our subjects.
PMID- 26422872
TI - The relation between oxidative stress parameters, ischemic stroke, and
hemorrhagic stroke.
AB - BACKGROUND/AIM: The aims of this study were to investigate the significance of
oxidative stress parameters in the pathogenesis of ischemic stroke and
hemorrhagic stroke and to investigate their effects on stroke severity using the
National Institutes of Health Stroke Scale (NIHSS). MATERIALS AND METHODS: A
total of 92 patients, including 74 with ischemic stroke and 18 with hemorrhagic
stroke, and 75 volunteers were enrolled in the study. Total oxidant status (TOS),
total antioxidant status (TAS), paraoxonase, stimulating paraoxonase,
arylesterase, and thiol levels were measured in both the patient and volunteer
groups. NIHSS and oxidative stress index (OSI) scores were calculated. RESULTS:
TOS and OSI levels were significantly higher in the ischemia and hemorrhagic
stroke groups than in the control group (P < 0.05). Arylesterase and thiol levels
were significantly lower in the ischemia group than the control group (P < 0.05).
No significant correlation was found between NIHSS score and TAS, TOS, OSI,
paraoxonase, arylesterase, stimulated paraoxonase, and thiol levels (P > 0.05).
CONCLUSION: Oxidative stress may play a role in the pathogenesis of both ischemic
stroke and hemorrhagic stroke in terms of oxidants. We do not think that
oxidative stress has any effect in determining stroke severity in either type of
stroke.
PMID- 26422873
TI - Asymmetric dimethylarginine is not a good predictor of ischemia using myocardial
perfusion scintigraphy.
AB - BACKGROUND/AIM: Asymmetric dimethylarginine (ADMA) plays role in the pathogenesis
of coronary artery disease and related mortality and morbidity through a number
of mechanisms. We hypothesized that plasma ADMA levels would be increased in the
presence of reversible ischemia as measured by GATED single photon emission
computed tomography (SPECT) myocardial perfusion scintigraphy (MPS). MATERIALS
AND METHODS: Fasting i.v. blood samples were drawn before testing. All patients
underwent 99mTc-sestamibi GATED SPECT MPS with a one-day stress-rest protocol;
the images were visually analyzed. Post-stress GATED parameters, including
ejection fraction, end systolic and end diastolic volumes, and automatic stress
defect scores, were recorded. RESULTS: The plasma ADMA levels were higher in the
ischemic group than in the non-ischemic group (0.46 +/- 0.19 vs. 0.40 +/- 0.15; P
= 0.016). Plasma ADMA levels (odds ratio [OR] = 13.5; 95% confidence interval
[CI] = 1.7-109.01; P = 0.015) and sex (OR = 2.49, 95% CI = 1.18-5.26; P = 0.017)
were independent predictors of ischemia. There was no linear correlation between
plasma ADMA levels and both the GATED SPECT and stress test parameters.
CONCLUSION: Our data support the hypothesis that increased baseline ADMA levels
are independently related with the presence of reversible ischemia.
PMID- 26422874
TI - Effects of pretreatment with esmolol and lidocaine on injection pain and
rocuronium-induced withdrawal response.
AB - BACKGROUND/AIM: We aimed to compare the effectiveness of esmolol 1 mg/kg and
lidocaine 1 mg/kg for injection pain and for the prevention of rocuronium-induced
withdrawal response. MATERIALS AND METHODS: We enrolled a total of 81 patients in
the study. Patients were randomly assigned to receive either 10 mL of 0.9% NaCl
(Group P), esmolol 1 mg/kg (Group E), or lidocaine 1.0 mg/kg (Group L). A
subparalyzing dose of rocuronium 0.05 mg/ kg was administered to all patients and
its effects were recorded. Anesthesia was induced with intravenous propofol and
intravenous rocuronium 0.5 mg/kg in all groups. The withdrawal movements of the
patient groups were subsequently graded. RESULTS: There was a statistically
significant difference in overall incidence of pain in group E and L compared to
the placebo group after administrating the subparalyzed dose (no pain response:
Group E = 81.5%, Group L = 77.8%, Group P = 14.8%) (P < 0.001). After intravenous
administration of an intubating dose of rocuronium, the esmolol group had a
significantly lower incidence of withdrawal movement than the other groups (no
response: Group E = 81.5%, Group L = 63%, Group P = 22.2%) (P < 0.001).
CONCLUSION: We found that esmolol significantly attenuates rocuronium-induced
withdrawal movement and also reduces pain when used at subparalyzing doses.
PMID- 26422875
TI - Herbal self-medication use in patients with diabetes mellitus type 2.
AB - BACKGROUND/AIM: A considerable number of patients suffering from diabetes
mellitus (DM) turn to self-medication using medicinal plants, preparations, and
medicine. The aim of this study was to investigate self-medication using
medicinal plants and the potential influence of health care professionals' advice
or media information regarding the use of herbal dietary supplements with
hypoglycemic effect in a population of patients with type 2 DM. MATERIALS AND
METHODS: This research, in the form of an analytic cross-sectional study, was
conducted in 6 pharmacies in the territory of Nis, Serbia, during October 2013.
The criterion set for the study was to include patients diagnosed with type 2
diabetes who used pharmacotherapy in addition to herbal supplements. RESULTS:
Surveyed women showed a statistically significant difference in the frequency of
using herbal supplements compared to men (P < 0.001). More frequent symptoms of
hypoglycemia were reported in the group of diabetic respondents who used herbal
dietary supplements (P < 0.05). The media was most responsible for influencing
decisions about self-medication that included the use of herbal dietary
supplements. CONCLUSION: The role of health professionals is indispensable and
very important, especially when the media is a potential cause of seeking self
medication.
PMID- 26422876
TI - Evaluation of patency following revision technique of high-velocity arteriovenous
fistula.
AB - BACKGROUND/AIM: The objective of this study is to report our experience with
surgical revision of dialysis access-induced ischemia syndrome. MATERIALS AND
METHODS: Between January 2005 and July 2013, 1254 patients underwent
arteriovenous fistula operation, and 86 of them [53 males, mean age: 55 +/- 25
(range: 25 to 75) years; 33 females, mean age: 50 +/- 20 (range: 30 to 70) years]
subsequently developed steal syndrome. These patients were treated with arterial
pressure-controlled polytetrafluoroethylene banding or constriction with
polypropylene suturing technique. Patients were followed in the outpatient clinic
at regular intervals. RESULTS: Symptoms were not relieved during the first 15
days in 4 patients; therefore, reintervention was performed. Thrombosis occurred
in one patient after reintervention. No early or late complications were detected
in other patients, and fistulae were suitable for hemodialysis. Patency rates at
6 and 12 months were 96% and 92%, respectively, and thrombosis rates were 7% and
9%. There was no hospital mortality in our study, but one patient died from
unrelated causes and two other patients quit follow-up after 6 months.
CONCLUSION: We think that arterial pressure-controlled surgical revision is an
effective and safe technique in patients with fistula-related hand ischemia.
PMID- 26422877
TI - Investigation of the effect of changes in muscle strength in gestational age upon
fear of falling and quality of life.
AB - BACKGROUND/AIM: The aim of this study is the investigation of the effect of
changes in muscle strength in gestational age upon fear of falling and quality of
life. MATERIALS AND METHODS: This longitudinal, descriptive study included a
sample of 37 pregnant women who volunteered to participate. The research data
were collected at 20 and 32 weeks of gestation. Data collection instruments
included a newly developed questionnaire form, the Tinetti Falls Efficacy Scale,
a visual analog scale, and the Turkish language version of the WHO Quality of
Life Scale. Upper body flexibility was measured by the back scratch test, while
muscle strength was measured by a handgrip dynamometer and balance by the
unipedal stance test. RESULTS: It was found that, as pregnancy advanced, pregnant
women had an increased fear of falling, as well as elevated systolic and
diastolic blood pressure levels. Participants suffered significant impairments in
their balance, handgrip strength, and quality of life within the physical,
psychological, and environmental domains. CONCLUSION: As pregnancy advances,
muscle strength decreases and the fear of falling experienced by pregnant women
increases, which significantly impairs the quality of life in the domains of
environment, physical, and mental health.
PMID- 26422878
TI - Risk factors and maximum standardized uptake values within lymph nodes of
anthracosis diagnosed by endobronchial ultrasound-guided transbronchial needle
aspiration.
AB - BACKGROUND/AIM: Enlarged mediastinal lymph nodes can result from serious
etiologies including granulomatous disease, neoplasia, etc., and a rare condition
called anthracosis . The aim of this study was to determine the incidence of risk
factors and the uptake values within the anthracotic lymph nodes. MATERIALS AND
METHODS: 106 patients who underwent endobronchial ultrasound transbronchial
needle aspiration and were diagnosed as having anthracosis were analyzed
retrospectively. Patients with positive confirmation by surgical biopsies or a 1
year follow-up period were enrolled. RESULTS: 201 lymph nodes were sampled from
106 patients. Subcarinal and interlobar lymph nodes were the most commonly
affected stations (36.8% and 34.3%, respectively). The mean durations of exposure
to biomass and cigarette smoke were 35.5 and 33 years, respectively. The mean
maximum standardized uptake value (SUVmax) within the lymph nodes was 4.76. The
SUVmax of the patients with associated malignancy was 4.19 and the SUVmax of
nonmalignant patients was 5.28. This difference was statistically significant (P
= 0.009). CONCLUSION: These findings suggest that anthracosis also affects the
mediastinal and hilar stations; it should be considered in differential diagnosis
in patients with mediastinal and hilar lymphadenopathies with intense uptake on
positron emission tomography scans, especially when there is a history of
exposure to known risk factors.
PMID- 26422879
TI - Value of prealbumin in assessment of nutrition for critically ill patients.
PMID- 26422880
TI - Reply to Letter to the Editor.
PMID- 26422881
TI - [THE INCENTIVE FOR SURGEONS TO IMPROVE THEIR MOTIVATION].
PMID- 26422882
TI - [NEW BOARD CERTIFICATION SYSTEM FOR SURGICAL SPECIALISTS].
PMID- 26422883
TI - [FRONTIER IN PERIOPERATIVE MANAGEMENT--ENHANCED RECOVERY AFTER SURGERY].
PMID- 26422884
TI - [IS EARLY ENTERAL FEEDING POSSIBLE?].
AB - In conventional postoperative management, early oral feeding after preoperative
oral supplementary water and gastrointestinal tract anastomosis was
contraindicated for two main reasons. Primarily, it was believed that it would be
dangerous because the gastrointestinal tract was in a physiological state of
paralytic ileus for 3-5 days after open surgery. The second reason for concern
was the risk of causing anastomotic suture rupture if patients did not rest
quietly until sufficient secondary wound healing of the gastrointestinal
anastomosis had occurred. However, this was counter to common sense, and the
current Enhanced Recovery after Surgery (ERAS) protocols recommend early oral
intake after preoperative oral supplementary water. This stimulates intestinal
tract motility and decreases complications. The ERAS protocols appear safe for
patient management after surgery involving the large intestine and are now being
assessed for patients undergoing upper gastrointestinal tract procedures.
PMID- 26422885
TI - [IMPACT OF PREOPERATIVE BOWEL PREPARATION ON PREVENTION OF SURGICAL SITE
INFECTION].
AB - Preoperative preparation of the bowel includes two methods, mechanical bowel
preparation (MBP) to remove gross feces and oral antibiotic bowel preparation
(OABP) to reduce the colonic bacterial load. MBP and OABP have been performed
since the 1940s to 1950s. MBP is routinely performed to reduce the morbidity and
mortality of elective colorectal surgery and has been a surgical dogma since the
early 1970s. However, numerous prospective, randomized, controlled trials and
meta-analyses have questioned the need for MBP in elective colorectal surgery,
and a meta-analysis showed that significantly more anastomotic leaks were found
after MBP. OABP decreases postoperative infectious complications considerably,
although the results differ with the type of antibiotic used. Recently, several
large retrospective studies have demonstrated that MBP plus OABP is associated
with reduced postoperative infectious complications including surgical site
infection rates after elective colorectal surgery. Further prospective,
randomized trials of MBP and OABP alone and in combination should be conducted.
PMID- 26422886
TI - [ANESTHESIA MANAGEMENT FOR ENHANCED RECOVERY AFTER SURGERY].
AB - In programs to enhance patient recovery after surgery, anesthesiologists play an
important role. In conventional management, patients managed with the
"starvation, stress, and drowning" regimen experience delays in the recovery
process. In contrast, anesthesiologists in the current perioperative management
scenario reduce the fasting period, maintain sufficient depth of anesthesia, and
administer appropriate infusion levels. In particular, three major factors
inhibiting postoperative recovery are known to be pain, gastrointestinal
dysfunction, and immobility. To prevent these, anesthesiologists should emphasize
pain control and manage patient care with the goals of early oral intake and
early mobility. It is important for surgeons and anesthesiologists to share
information and techniques to promote postoperative recovery. Multidisciplinary
cooperation can be expected to have synergistic effects leading to improved
safety, better treatment outcomes, and smooth perioperative management.
PMID- 26422887
TI - [OBJECTIVE ASSESSMENT OF POSTOPERATIVE PAIN AFTER DIGESTIVE TRACT SURGERY].
AB - Pain is a sensation associated with subjective factors, making it difficult to
measure and assess. Currently, there is no widely accepted method of objectively
assessing pain, and therefore subjective assessments such as the Visual Analogue
Scale (VAS) are generally used. The PainVision system has been developed for the
quantitative analysis of pain and comparison of postoperative pain intensity. In
this study, we investigated whether postoperative pain could be objectively
assessed using this system in digestive tract surgery patients. Pain scores were
measured with the VAS, the PainVision system, and the short-form McGill Pain
Questionnaire in patients undergoing open or laparoscopic hepatectomy, open or
laparoscopic gastrectomy, and laparoscopic cholecystectomy. As measured using the
PainVision system, postoperative pain intensity was lower in patients who
underwent laparoscopic surgery compared with open hepatectomy. In open
hepatectomy patients, pain intensity measured by the PainVision system was
significantly lower on postoperative days (POD) 7 and 10 than on POD 1.
Preemptive use of nonsteroidal antiinflammatory drugs significantly reduced
postoperative pain in open hepatectomy patients. The results showed that
PainVision effectively quantifies pain intensity after digestive tract surgery.
Objective assessment of postoperative pain may lead to earlier mobility and
improved quality of life.
PMID- 26422888
TI - [EFFECTS AND LIMITATIONS OF PREOPERATIVE CARBOHYDRATE LOADING: A REVIEW FROM THE
VIEWPOINT OF ITS MECHANISM OF ACTION].
AB - Preoperative carbohydrate loading has been adopted as an integral part of many
enhanced-recovery or fast-track surgery programs. The main aim is to reduce
postoperative insulin resistance (IR), thereby allowing for effective
postoperative nutrition with more anabolic properties and less risk of
hyperglycemia, which may improve postoperative outcomes. Based on the mechanism
underlying postoperative IR, preoperative carbohydrate loading can inhibit only
the exacerbating peripheral IR caused by excessive circulating concentrations of
free fatty acids secondary to starvation but not the peripheral and central IR
induced by stress hormones and inflammatory cytokines released as part of the
surgical stress response, suggesting that preoperative carbohydrate loading may
have only limited benefit. The Cochrane review of the effects of preoperative
carbohydrate treatment (published in 2014) provided results that were completely
consistent with the legitimate expectation described above, i.e., a small
reduction of uncertain clinical significance in the length of hospital stay and
little or no effect on postoperative complications or other important clinical
outcomes, despite increased postoperative peripheral insulin sensitivity. Because
preoperative carbohydrate loading has only limited benefit both theoretically and
clinically, we should complement its effect through the introduction of a less
invasive approach capable of attenuating surgical stress-mediated IR.
PMID- 26422889
TI - [EARLY AMBULATION AFTER SURGERY AND PERIOPERATIVE REHABILITATION].
AB - Early ambulation following a surgical procedure is a central concept in fast
track surgery according to Enhanced Recovery after Surgery protocols. Although a
shorter hospital stay is reported to be a benefit of perioperative
rehabilitation, its effect on patient metabolism has not been fully explored.
Thirty-eight patients who had undergone esophagectomy, a highly stressful
surgery, received intensive rehabilitation (group R) with regular evaluation of
their metabolic parameters compared with 41 control group patients (group C) who
received conventional care without such rehabilitation. Nitrogen balances
calculated daily were significantly higher in group R on the third postoperative
day. Fluid retention after surgery improved earlier in group R than in group C.
Liver dysfunction occurred 1 week after surgery in group C but was avoided in
group R. Total lymphocyte counts decreased after surgery in both groups, but
their recovery was observed earlier in group R. Early mobility after
esophagectomy is thought to avoid disuse atrophy of skeletal muscles in
postsurgical patients. Fluid retention and immune dysfunction are also improved
through perioperative rehabilitation. The biological mechanisms underlying the
benefits of rehabilitation should be further elucidated for its clinical
application in all surgical care pathways.
PMID- 26422890
TI - [PRESENT MAJOR ISSUES OF CLINICAL TRIALS IN JAPAN].
PMID- 26422891
TI - [WHAT WE CAN LEARN FROM A CASE OF MEDICAL MALPRACTICE--PATIENT AWARDED DAMAGES
FOR A CLAIM THAT A NON-STROKE SPECIALIST RULED OUT A DIAGNOSIS OF TRANSIENT
ISCHEMIC ATTACK (TIA) DESPITE HIS CLINICAL PRESENTATION OF TIA OR A STRONG
SUSPICION THEREOF].
PMID- 26422892
TI - [PERIANAL PROCEDURE FOR THE TREATMENT OF RECTAL PROLAPSE].
PMID- 26422893
TI - [THE ROLE OF NURSE PRACTIONER AND PHYSICIAN ASSISTANT IN CARDIOTHORACIC SURGERY
AT NYU MEDICAL CENTER--COMPARED WITH JAPANESE INSTITUTION].
PMID- 26422894
TI - [COMMUNITY HOSPITAL OF THE MONTEREY PENINSULA DIABETES AND NUTRITION PROGRAM
FAMILY NURSE PRACTITIONER].
PMID- 26422895
TI - [OPERATIONAL EXPERIENCE OF AUTOMATIC POSTING SYSTEM TO THE NATIONAL CLINICAL
DATABASE USING FILEMAKER PRO].
AB - We would like to introduce a semi-automated registration system for the National
Clinical Database. Japan Surgery Society runs the National Clinical Database
since January 2011. And automated registration system is long-awaited due to the
number of cases and diverse items to register. Well-known database management
system, FileMakerPro enabled collecting and registering the items to the web-site
automatically. Still some items need to copy one by one, but after filling the
data, all data would be input to the web page for registration. Merit for this
automated system is increasing not only the efficiency of administration work but
the quality and the usefulness of this database. This paper is to report the
outline of the registration system to the NCD database.
PMID- 26422897
TI - PPP.
PMID- 26422896
TI - [A REPORT FROM THE 132ND CONGRESS OF THE GERMAN SURGICAL SOCIETY].
PMID- 26422898
TI - Visual directional anisotropy does not mirror the directional anisotropy apparent
in postural sway.
AB - Presenting a large optic flow pattern to observers is likely to cause postural
sway. However, directional anisotropies have been reported, in that contracting
optic flow induces more postural sway than expanding optic flow. Recently, we
showed that the biomechanics of the lower leg cannot account for this anisotropy
(Holten, Donker, Verstraten, & van der Smagt, 2013, Experimental Brain Research,
228, 117-129). The question we address in the current study is whether
differences in visual processing of optic flow directions, in particular the
perceptual strength of these directions, mirrors the anisotropy apparent in
postural sway. That is, can contracting optic flow be considered to be a
perceptually stronger visual stimulus than expanding optic flow? In the current
study we use a breaking continuous flash suppression paradigm where we assume
that perceptually stronger visual stimuli will break the flash suppression
earlier, making the suppressed optic flow stimulus visible sooner. Surprisingly,
our results show the opposite, in that expanding optic flow is detected earlier
than contracting optic flow.
PMID- 26422899
TI - Dimensional interaction in distance judgment.
AB - Participants decided under speed stress whether or not the horizontal distances
between pairs of frontal locations exceeded a criterion distance. The error rate
reflected parallel effects of the horizontal and vertical distance between the
locations. Whereas dimensional interaction in perceptual judgment has previously
been attributed either to the perception of the stimulus or to the response
decision concerning the stimulus, here dimensional interaction was attributed to
the process of distance assessment regarding the test locations. Under the
proposed account, the horizontal distance between the locations could not be
assessed independently of the vertical distance. Only the overall distance
between the locations could be assessed. However, because the horizontal and
vertical positions of the locations could be independently assessed, the
horizontal distance between the locations was available to the extent that the
vertical positions of the locations were weighted so as to minimize vertical
distance prior to the assessment of overall distance. In support of this account,
parallel effects of horizontal and vertical distance were not observed when
participants decided whether or not pairs of locations had the same horizontal
position.
PMID- 26422900
TI - Global shape information increases but color information decreases the composite
face effect.
AB - The separation of visual shape and surface information may be useful for
understanding holistic face perception--that is, the perception of a face as a
single unit (Jiang, Blanz, & Rossion, 2011, Visual Cognition, 19, 1003-1034). A
widely used measure of holistic face perception is the composite face effect
(CFE), in which identical top face halves appear different when aligned with
bottom face halves from different identities. In the present study the influences
of global face shape (ie contour of the face) and color information on the CFE
are investigated, with the hypothesis that global face shape supports but color
impairs holistic face perception as measured in this paradigm. In experiment 1
the CFE is significantly increased when face stimuli possess natural global shape
information than when cropped to a generic (ie oval) global shape; this effect is
not found when the stimuli are presented inverted. In experiment 2 the CFE is
significantly decreased when face stimuli are presented with color information
than when presented in grayscale. These findings indicate that grayscale stimuli
maintaining natural global face shape information provide the most adept measure
of holistic face perception in the behavioral composite face paradigm. More
generally, they show that reducing different types of information diagnostic for
individual face perception can have opposite effects on the CFE, illustrating the
functional dissociation between shape and surface information in face perception.
PMID- 26422901
TI - Eye shape illusions induced by eyebrow positions.
AB - We investigated whether the position of the eyebrows influences the perceived
shape of the eyes by employing psychophysical measurements. Experiment 1 used
arched and straight eyebrows at five different inclinations as stimuli and
measured the perceived inclination of the eyes. The results demonstrated that the
eyes are perceived to be somewhat inclined in the same direction as the eyebrows.
Experiment 2 measured the perceived eye size by manipulating the distance between
the eyes and the eyebrows and the curvature of the eyebrows across three levels.
The results showed that the lower eyebrows (ie closer to eyes) made the eyes
appear larger and the higher eyebrows made the eyes appear smaller, while eyebrow
curvature had no effect on perceived eye size. Experiment 3 examined the role of
the eye-eyebrow distance in the eye inclination illusion shown in experiment 1.
The eye inclination illusion was unaffected by the eye-eyebrow distance,
suggesting that the eye inclination illusion and the eye size illusion may
involve different kinds of assimilation. These illusions are discussed in terms
of face perception and possible practical applications.
PMID- 26422902
TI - Unbiased measures of interocular transfer of motion adaptation.
AB - Numerous studies have measured the extent to which motion aftereffects transfer
interocularly. However, many have done so using bias-prone methods, and studies
rarely compare different types of motion directly. Here, we use a technique
designed to reduce bias (Morgan, 2013, Journal of Vision, 13(8):26, 1-11) to
estimate interocular transfer (IOT) for five types of motion: simple
translational motion, expansion/contraction, rotation, spiral, and complex
translational motion. We used both static and dynamic targets with subjects
making binary judgments of perceived speed. Overall, the average IOT was 65%,
consistent with previous studies (mean over 17 studies of 67% transfer). There
was a main effect of motion type, with translational motion producing stronger
IOT (mean: 86%) overall than any of the more complex varieties of motion (mean:
51%). This is inconsistent with the notion that IOT should be strongest for
motion processed in extrastriate regions that are fully binocular. We conclude
that adaptation is a complex phenomenon too poorly understood to make firm
inferences about the binocular structure of motion systems.
PMID- 26422903
TI - Aesthetic preference in the spatial composition of traditional Chinese paintings.
AB - Aesthetic psychology has discussed many aspects of aesthetic preferences for
spatial composition. However, there have been few empirical explorations of the
spatial composition of traditional Chinese paintings. The results of this
experiment showed that the shape of the frame had a significant effect on
aesthetic preferences. Participants preferred to put two figures at certain
relative horizontal distances from each other according to the horizontal shape
of the frame but may have difficulty in adapting the relative vertical distance
according to the vertical shape of the frame. Furthermore, the unique aesthetic
interest of traditional Chinese long-vertical scroll paintings was discussed.
This discussion revealed that, in a creative way, ancient Chinese artists
followed the same aesthetic principles we observed, and they developed the
artistic conception and romantic charm of traditional Chinese paintings.
PMID- 26422904
TI - The sensory experiences of adults with autism spectrum disorder: A qualitative
analysis.
AB - It has been well established that individuals with autism spectrum disorder
report unusual experiences with sensory stimuli compared with typically
developing individuals. However, there is a paucity of research exploring the
nature of such experiences. A focus group was conducted with six adults with a
diagnosis of autism or Asperger syndrome. Data were coded and analysed using an
inductive, qualitative thematic analysis. Four main themes encompassing both
positive and negative sensory experiences emerged from these data: (a) the
importance of particular aspects of stimuli in their perception, (b) the
importance of having control over stimuli, (c) how emotions/mental states could
impact/be impacted by sensory stimuli, and (d) physical responses to stimuli.
These data are discussed alongside extant literature. Limitations, possible
implications, and potential directions of future research are also discussed.
PMID- 26422906
TI - The reference point for monocular visual direction can, sometimes, be one of the
eyes rather than the cyclopean eye.
AB - We found that the imaginary line passing through two stimuli that points to an
eye appears to do so when seen monocularly, which is consistent with
Porterfield's axiom but inconsistent with Wells's proposition regarding visual
direction. We also found that the imaginary line appears to point to the bridge
of the nose when the near stimulus is seen binocularly and the far one is seen
monocularly, which is consistent with Wells's proposition but inconsistent with
Porterfield's axiom. We argue that these findings themselves do not necessarily
vitiate the axiom or the proposition and that one should explore the different
experimental conditions and hypothesize about the processes that might be
involved.
PMID- 26422905
TI - The effect of age and gender on pressure pain thresholds and suprathreshold
stimuli.
AB - OBJECTIVES: The study investigates the impact of age and gender on (1)
experimental pressure pain detection thresholds (PPDT) and pressure pain
tolerance thresholds (PPTolT) and (2) participants' self-reports of pain
intensity and unpleasantness at suprathreshold and subthreshold levels. METHODS:
twenty young (20-34, mean age = 24.6 +/- 3.6 years, ten female) and twenty
elderly (65-88, mean age = 73.6 +/- 6.6 years, ten female) healthy volunteers
were compared. Mini-Mental State Examination (MMSE 28-30) assessed intact
cognitive functioning. Pain thresholds were assessed together with the sensory
intensity ratings to 1.3 x PPDT (pain) and 0.2 x PPDT (no pain). RESULTS: PPDT
and PPTolT significantly decreased with age and were lower in young females as
compared with young males. No gender differences were observed in the elderly
group. PPDT decreased significantly with age in males but not in females.
Conversely, the intensity and unpleasantness of the pain stimulus were
significantly rated lower in the elderly as compared with the young. No gender
differences were observed in the report of intensity and unpleasantness of the
stimulations. DISCUSSION: A mismatch in pain sensitivity, tolerance, and pain
self-reports was observed. Findings suggest that pain experiences in the elderly
differ from the experiences in the young on multiple dimensions: sensory,
affective, and cognitive. Findings may also indicate that the elderly appraise
pain experiences using different psychological strategies.
PMID- 26422908
TI - [[The most frequent vices of authors of medical publications]].
PMID- 26422909
TI - [Contraception in women with chronic diseases].
AB - BACKGROUND: Almost 10% of women in reproductive age had a chronic disease, and
contraception is frequently ignored by these patients. The lack of use of
contraceptives methods has a higher repercussion in these patients; if pregnant,
the risk is increased in morbidity and feto-maternal mortality. OBJECTIVES: to
know the contraceptive coverage in women with chronic degenerative diseases, the
kind of contraceptive methods and the unsatisfied demand. MATERIAL AND METHODS: A
descriptive study was made with the application of a survey from the one
elaborated by the IMSS. It explores contraception socio-demographic data, causes
of non-protection and also explores Medical Doctor (MD) participation. Sample
size was calculated in 385 women in reproductive age with a chronic disease.
RESULTS: 428 women about 30-49 years old were interviewed, 53% of them were
married, they had various diseases, the contraceptive coverage was 84%. The
definitive methods were the most used with 47%, followed by the condom with 20%,
intrauterine device with 13% and others in minor proportion. 38.5% of patients
with sexual life have risk of pregnancy for lack of use of method or for using
one of low effectiveness and continuity. Of 45 (16%) patients with sexual life
that did not use methods, 29% because they wish pregnancy, 18% by collateral
effects and the rest for other causes. From this same patients 21 wished getting
pregnant and 24 did not, this is an unsatisfied demand of 53%. The MD's informed
about risks in case of pregnancy of 83.4% of the patients. CONCLUSIONS: The
contraceptive coverage is low and the unsatisfied demand is higher than in the
general population. It requires the effective participation of health personal in
this group of high reproductive risk.
PMID- 26422910
TI - [Neddle-guided biopsy in the diagnosis of non-palpable breast cancer].
AB - OBJECTIVE: To estimate the diagnostic accuracy of the spearfishing or neddle
guided biopsy to breast cancer and no palpable mammography and ultrasound
findings suspicious for malignancy. MATERIAL AND METHODS: Observational,
transversal, prolective, and descriptive study was made. A histopathological
diagnosis were conducted from August 2004 to December 2011 in the Radiology and
Image Departmen of Centro Medico La Raza to patients sent by the service of
Surgical Oncology-with non-palpable breast findings identified by mammography
and/or ultrasound with any suspicion of malignancy. Radiographic and
ultrasonographic images of the specimen were obtained after the surgical
procedure. RESULTS: Harpoon 532 placements with histopathological report.
Malignancies were 4.0% of the biopsies were performed in negative mammograms (ACR
BI-RADS(r) 3) and 34.3% (p <= 0.05) of which were performed in positive
mammography: 19.5% of mammograms ACR BI-4 and RADS(r) 89.7% (p < 0.0001) of
mammograms ACR BI-RADS(r) 5. The negative mammography (ACR BI-RADS(r) 3) which
resulted in cancer occurred in a patient with a personal history of breast cancer
who had a solid nodule in one breast. In the evaluation of mammography studies
and placing seven harpoons participated certified radiologists and additional
qualification in breast imaging, and five radiology technicians trained in
mammography. CONCLUSIONS: The positive cases in the evaluation of mammography
studies and placing seven harpoons participated certified radiologists and
additional qualification in breast imaging, and five radiology technicians
trained in mammography. (sum of the ACR BI-RADS(r) cases 4 and ACR BI-RADS(r) 5)
and individual cases ACR BI-RADS(r) 4 had a PPV within recommended ranges ACR BI
RADS(r); PPV ACR BI-RADS(r) may was lower than recommended by the literature,
although most recommended by other series, which forces us to emphasize adherence
to the semiotics suggested by ACR BI-RADS(r) and avoid unnecessary surgery.
Patients with a personal history of breast cancer and finding a new ACR BI
RADS(r) 3 should have an individual assessment and consider biopsy before the
short-term monitoring.
PMID- 26422911
TI - [Perinatal complications and serotonin level (5-HT) associated with low birth
weight].
AB - BACKGROUND: Studies in human and in experimental models suggest that interaction
among the adverse prenatal and postnatal environment increases susceptibility for
chronic diseases. This environment could induce changes in the metabolism
balance. OBJECTIVE: To analyze how the low birth weight (LBW) influences on the
perinatal complications and serotonin serum concentration associated with the
possible changes in the alimentary behavior. MATERIAL AND METHODS: A prospective,
longitudinal and descriptive study was made during 6 months of the obstetric
events to know the frequency and complications of LBW. To evaluate if these
complications could have some relationship with the serotonin concentration we
measured through their metabolite 5-hidroxitriptamina (5-HT) and the possible
chronic illnesses of the adult life. RESULTS: From 1,418 obstetric events
attended during the study period, 506 patients with viable pregnancies and met
the inclusion criteria were included, 26.8% had LBW and the immediate clinical
complications were presented in 52.2% of them and serum concentration 5-HT of
362.2 +/- 21.8 vs 82.1 +/- 13.6 ng/mL. CONCLUSION: Low birth weight, besides
causing perinatal complica- tions, also conditions permanent changes in the
expression of satiety neurotransmitters and some tissues, that alter the
regulation mechanisms to maintain the energy balance leading to metabolic
stability, which is needed to the proper endocrine functioning in the adult life
of these individuals.
PMID- 26422912
TI - [Interobserver diagnostic agreement on digital images of hysteroscopic studies].
AB - BACKGROUND: Hysteroscopic studies are of the most used methods to examine the
uterine cavity in patients that present abnormal uterine hemorrhage as well as
those patients with infertility. The use of hysteroscopic studies during
reproductive cycles has increased the successful of pregnancy rates. Up to date,
there are not many studies evaluating the inter-observer agreement in the
diagnosis of different uterine pathology when using a hysteroscopic study.
OBJECTIVE: To evaluate the inter-observer agreement in the diagnosis of uterine
pathology when using digitalized images in hysteroscopic studies made by
residents of gynecological endoscopy. MATERIALS AND METHODS: A cross-sectional,
descriptive and observational study was made including 28 images of hysteroscopic
studies selected by at least two of three experts in hysteroscopy, who determined
that they were adequate to do a diagnostic impresion. From a total of four
residents, two were selected using a randomized sampling. The images were shown
to each resident in a randomized presentation and the diagnosis agreement was
evaluated. Kappa test was used to evaluate the interobserver agreement with 95%
confidence interval. RESULTS: The interobserver agreement obtained by Kappa test
for different images for diagnosis of uterine pathology were: normal uterine
cavity (kappa = 0.81 with CI 95%, 0.56-1.00), endometrial polypus (kappa = 0.71
with CI 95%, 0.33-1.00), submucous myoma (kappa = 0.71 with Cl 95%, 0.33- 1.00),
intrauterine adherences (kappa = 0.84 with Cl 95%, 0.52-1.00), uterine septum
(kappa = 0.76 with CI 95%, 0.43-1.00) and endometrial hyperplasia or potential
endometrial cancer (kappa = 0.87 with Cl 95%, 0.61-1.00). CONCLUSIONS: The
interobserver agreement using digitalized images in the diagnosis of different
uterine pathology from hysteroscopic studies made by residents of endoscopic
surgery was high and very high in all cases.
PMID- 26422913
TI - [Hysteroscopic polypectomy, treatment of abnormal uterine bleeding].
AB - OBJECTIVES: To evaluate the effectiveness of the hysteroscopic polypectomy in
terms of the decrease of the abnormal uterine bleeding. METHODS: A cross
sectional and analytical study was done with patients to whom a hysteroscopic
polypectomy was done for treating the abnormal uterine bleeding, between January
2009 and December 2013. The response to the treatment was evaluated via a survey
given to the patients about the behavior of the abnormal uterine bleeding after
the procedure and about overall satisfaction. RESULTS: The results were obtained
after a hysteroscopic polypectomy done to 128 patients and were as follows. The
average time from the polypectomy applied until the survey was 30.5 months, with
a standard deviation of 18 months. 67.2% of the patients reported decreased
abnormal uterine bleeding and the 32.8% reported a persistence of symptoms. On
average 82.8% of the. patients were satisfied with the treatment. Bivariate and
multivariate analysis showed no association between the variables studied and no
improvement of abnormal uterine bleeding after surgery (polypectomy). There were
no complications. CONCLUSION: Hysteroscopic polypectomy is a safe surgical
treatment, which decreases on two of three patients the abnormal uterine bleeding
in the presence of endometrial polyps, with an acceptable level of satisfaction.
PMID- 26422914
TI - [Rate of human papillomavirus infection in rural areas diagnosed by direct
visualization with acetic acid and lugol].
AB - BACKGROUND: Infection by HPV is a major global health problem and the main risk
factor for cervical cancer with high morbidity and mortality. Simple diagnostic
methods, such as visual inspection with the naked eye of the cervix with acetic
acid application 5% (VAT) or solution of iodine (tincture of iodine) are simple
to detect early lesions, sensitivity varies from 87 to 99% and specificity varies
from 23 to 87%. OBJECTIVE: To find the proportion of infection by human
papillomavirus in a population of extreme poverty. MATERIAL AND METHOD: Linear,
observational and descriptive pilot study was done in patients of marginalized
communities in extreme poverty in Chiapas (Mexico), from 1 to 30 November 2013.
The existence of acetowhite lesions suggestive of virus was verified human
papillomavirus, and medical history of all patients was formed for the incidence
of risk factors. RESULTS: 214 women with age limits of 19 and 78 years, median
age of 37 years were studied. Of the total, 66 (31%) had acetowhite lesions
consistent with human papillomavirus at the time of the study. CONCLUSIONS:
Marginalized populations have a higher risk of infection with human
papillomavirus, consequently high rate of progression to cervical cancer due to
sociodemographic characteristics, risk factors and lack of resources in health.
Diagnostic tests like the simple display with acetic acid are ideal for people
such as this.
PMID- 26422915
TI - [Risk factors of evolution of postpartum hemorrhage towards severe postpartum
hemorrhage: A case-control study].
AB - OBJECTIVE: To describe the incidence and risk factors for evolution of postpartum
haemorrhage towards severe. MATERIAL AND METHODS: Epidemiologic, observational,
analytical, case-control study was done from total data of deliveries in Complexo
Hospitalario de Ourense between January 1st 2004 and June 30th 2014. Mann-Whitney
U test was used to determine the differences between cases and controls. The
statistical analyses were made with the informatic programs Spss 15.0 y Epidat
3.0. We considered statistical significance for p < 0.05. RESULTS: The initial
size of the sample was 17,116 deliveries from which we selected 150 patients with
the diagnosis of postpartum haemorrhage. The incidence for HPSe form all
deliveries was 3.3% reaching 36% of the total of postpartum haemorrhages. 79.63%
of HPSe showed symptoms withing the first 24h postpartum, but we found that
20.37% debuted as secondary postpartum haemorrhages. BMI >= 35, hypertensive
gestational manifestations, labor's second phase >= 120 minutes and weight at
birth > 4000 g presented statistical significance as risk factor for evolution to
severe postpartum haemhorrage. The relative risk for evolution towards HPSe was
2.81 for instrumental delivery and 3.55 for cesarean section. The most prevalent
etiology was uterine atony. CONCLUSION: The incidence of HPSe in our hospital is
low, as well as secondary maternal mortality. The major risk factor for the
appearance of the clinical symptoms is cesarean section, followed, in less
proportion by instrumental delivery. It is possible for the HPSe to make its
appearance delayed after delivery, usually secondary to infrequent and non well
known clinical presentations.
PMID- 26422916
TI - [Influence of age on laparoscopic colposacropexy].
AB - OBJECTIVES: To evaluate the influence of age on laparoscopic colposacropexy (LCS)
outcome and complications for pelvic organ prolapse. MATERIAL AND METHODS: A
retrospective and comparative study of 105 patients who underwent standard LCS
for Baden-Walker graded pelvic organ prolapse from February 2002 to March 2015.
They were categorized into two groups according to age. Group 1 consisted in <=
50 years old patients and included 55 women. Group 2 included 50 women who were
>= 60 years old. Outcomes and complications were compared in both groups.
RESULTS: Previous history of abdominal surgery or surgery for pelvic floor
disorders was significantly greater in group 2 (43.6 vs 70%). There was no
significant difference regarding urinary stress incontinence, urge incontinence
or severe organ prolapse between groups (47.2 vs 36%; 1.8 vs 8% and 90.9 vs 92%
for Groups 1 and 2 respectively). Although a statistically significant greater
proportion of vaginal vault prolapse was present in the elderly group (16.3 vs
38%), the same LCS surgical technique was used in both groups of patients.
Despite operating time was significantly greater in the younger group (205.8 +/-
53.4 minutes in Group 1 vs 182 +/- 42.3 minutes in Group 2), hospital stay was
similar in both groups (2.9 +/- 1.1 days vs 3.0 +/- 1.9 days in group 1 and group
2 respectively). Postoperative complications were not severe and there were no
clinically significant differences between groups (20 vs 14%). We found no
statistically differences between groups when comparing cure rates (87 vs 92%) in
groups 1 and 2 respectively, patient satisfaction and postoperative anatomical
findings. CONCLUSIONS: LCS has shown excellent cure rates in both young and elder
female patients with pelvic organ prolapse.
PMID- 26422917
TI - [Abdominal ectopic pregnancy. A case report and literature review].
AB - Abdominal ectopic pregnancy is an extremely rare entity, which represents 1% of
all ectopic pregnancies and is associated with high maternal and fetal morbidity
and mortality. The maternal mortality risk of an abdominal ectopic pregnancy is
seven to eight times greater than the risk of a tubal ectopic pregnancy and is 90
times greater than the risk of intrauterine pregnancy. This is a disease of
difficult diagnosis that often takes place late. We report the case of a patient
with an abdominal ectopic pregnancy, which was diagnosed by abdominal ultrasound
in the second trimester; the patient was suc- cessfully treated with exploratory
laparotomy with complete removal of the fetus and placenta. We provide a review
of the literature on the risk factors for abdominal ectopic pregnancy, diagnostic
tests and therapeutic options.
PMID- 26422918
TI - [SCREENING AND SELECTION OF THE SOIL MICROORGANISMS ON THE ABILITY OF "NITROGEN
FIXING ACTIVITY"].
AB - The isolates of microorganisms from the rhizosphere of spring barley plants and
soil at the use of analytical selection method was isolated. Its isolates on the
ability of "nitrogen-fixing activity" was tested. It was shown that isolates of
microorganisms had different of the colonies formed and cultural growth on the
Eshbi's selective medium as well as the ability to fixing of molecular nitrogen.
The different levels of intensity and dynamics of isolates nitrogenase activity
in vitro were identified. New isolates of the soil microorganisms complement of
the gene pool diazotrophic bacteria. Its isolates are perspectivity for the study
as the basis or components of the bacterial fertilizers for the crops.
PMID- 26422919
TI - [INFLUENCE OF FUNGICIDES COMPLEX INOCULUM EKOVITAL ON RHIZOSPHERE
MICROBIOCENOSIS, DISEASES RESISTANCE AND SOYBEEN PRODUCTIVITY].
AB - It has been investigated the effect of fungicide with systemic action of Vitavaks
200 FF, Maxim Star 025 FS, Kinto duo and the complex inoculum Ekovital on
rhizospheric microbial communities, diseases resistance and soybean productivity
of Annushka biovar. The combined use of fungicides and inoculation has
contributed to better formation of nodulation apparatus (the number of nodules on
the roots was increased in 1.3-2.8 times), resistance increase to soybean
pathogens septoriosis and ascochitosis, plant productivity increase on 17.4-32.1%
relatively to the variant with Ekovital. The efficiency of the combined treatment
of seeds against septoriosis and ascochitosis has become 45.8-64.1% and 82.0
95.1% respectively, in the flowering-early fruiting stage and 38.1-60.6% and 70.3
82.1% respectively, in the loading beans phase.
PMID- 26422920
TI - [THE EFFECT OF METAL IONES AND SPECIFIC CHEMICAL REAGENTS ON THE ACTIVITY OF
ASPERGILLUS FLAVUS VAR. ORYZAE AND BACILLUS SUBTILIS alpha-AMYLASES].
AB - The effect of cations and anions on the activity of Aspergillus flavus var.
oryzae and Bacillus subtilis alpha-amylases showed that the tested enzymes are
sensitive to most of cations and resistant to anions. The most significant
inhibitory effects on the activity of A. flavus var. oryzae alpha-amylase have
been demonstrated by Al3+ and Fe3+ ions, while on the activity of B. subtilis
alpha-amylase - Hg2+, Cu2+ and Fe3+ ions. Inactivation of A. flavus var. oryzae
and B. subtilis alpha-amylases in the presence of EGTA is indicated on the
presence within their structure of metal ions. An important role in the enzymatic
catalysis of both enzymes play carboxyl groups as evidenced by their inhibition
of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide methiodide. Inhibition of B.
subtilis alpha-amylase by p-chloromercuribenzoate, N-ethylmaleimide and sodium
sulfite is indicated on the probable involvement of the sulfhydryl groups in the
functioning of the enzyme. Unlike most studied glycosidases the tested enzymes do
not contain histidine imidazole group in the active center.
PMID- 26422921
TI - [OPTIMIZATION OF CULTIVATION CONDITIONS OF PENICILLIUM TARDUM--THE alpha-L-
RHAMNOSIDASE PRODUCER].
AB - The influence of some technological cultivation parameters of Penicillium tardum
to synthesize of the extracellular alpha.-L-rhamnosidase were studied. It was
shown that rhamnose (0.8%), yeasts autolysate (0.2%), temperature of the
cultivation 25 degrees C, pH 5.0 are necessary for maximal alpha-L-rhamnosidase
production. The enzyme reaches the maximal activity level in 96 hours with
sulphitic number equal 0.44. At cultivation of P. tardum in the picked up
conditions the alpha-L-rhamnosidase synthesis has raised in 4 times.
PMID- 26422922
TI - [EFFECT OF MICROSCOPIC FUNGI ON COMPONENT COMPOSITION OF RUBBER SCN-18].
AB - Resistance to the action of microscopic fungi of the material SCN-18, which had
been characterized by high resistance to microscopic fungi was idefenited. It has
been noted that in the case of using of test cultures of fungi isolated from the
rubber substrates, the intensity of damage of the SCN-18 was higher than in the
case of using of species proposed by GOST 9.049-91. During 1-year trial of
resistance to the action of microscopic fungi of SCN-18 it had been set
decreasing of the amount of ester groups in the studied material, which indicated
about gradual degradation of the plasticizer dibutylphthalate, which was included
to the component composition of SCN-18.
PMID- 26422923
TI - THE EFFECT OF P-NITROCHLOROBENZENE ON HOMEOSTASIS QUANTITATIVE PARAMETERS OF
KARST CAVE CLAYS AND ECUADOR SOILS MICROBIAL COMMUNITIES.
AB - In this paper it was given the effect of p-nitrochlorobenzene (NCB) on the
homeostasis quantitative parameters of cave clays microbial communities from
Western Ukraine and Abkhazia (Mushkarova Yama, Kuybushevskaya) and soils of
Ecuador tropical ecosystems. For these microbial communities were determined
maximum permissible concentrations and types of responses on xenobiotic.
Microbial communities of Mushkarova Yama cave clays and rainforest soils of
Ecuador were characterized by the first type of response. Microbial communities
of Kuybushevskaya clays and mountain jungles of Ecuador were characterized by the
second type of response. Maximum permissible concentration of NCB for Mushkarova
Yama was 200 mg/l, for the other studied microbial communities--300 mg/l. It was
shown, that microbial communities were not only highly resistant to NCB but also
interacted with it by destroying this xenobiotic and decreasing its concentration
in 4 times.
PMID- 26422924
TI - RESISTANCE OF MICROBIAL COMMUNITIES FROM ECUADOR ECOSYSTEMS TO REPRESENTATIVE
TOXIC METALS - CrO4(2-), Co2+, Ni2+, Cu2+, Hg2+.
AB - Microbial communities of the Ecuadorian Andes and volcano Tungurahua were shown
to be super resistant to representative toxic metals. Maximum permissible
concentrations of toxic metals were 100 ppm of Hg2+, 500 ppm of Co2+ and Ni2+,
1000 and 1500 ppm of Cr(VI), 10000 and 20000 ppm of Cu2+. The effect of metal
concentration increasing on the biomass growth, CO2 and H2 synthesis was
investigated. Two types of response of microbial communities on the increasing of
toxic metals concentrations were discovered. The first type of response is the
catastrophic inhibition of microbial growth. The second type of response is the
absence of microbial growth inhibition at certain metal concentration gradient.
The succession of qualitative structure of Ecuadorian microbial communities was
shown for the first time. Bacteria, yeasts and finally fungi consistently
dominate in the microbial community at the Cu2+ concentration raising.
Microorganisms resistant to ultra-high concentrations of toxic metals (e.g., 3000
... 20000 ppm of Cu2+) were isolated from Ecuadorian ecosystems. These
microorganisms are able to accumulate toxic metals.
PMID- 26422925
TI - THE WIDESPREAD OF Fe(III)-REDUCING BACTERIA IN NATURAL ECOSYSTEMS OF ECUADOR.
AB - The widespread of Fe(III)-reducing microorganisms in natural ecosystems of
Ecuador of La Favorita, Tungurahua volcano and Papallacta areas was
experimentally proved. High efficiency of microbial precipitation of soluble iron
compounds was also demonstrated. Obtained results indicate the potential ability
of Fe(III)-reducing microorganisms to influence the formation of carbon and iron
vector fluxes in ecosystems, as well as development of effective biotechnologies
of water purification from iron compounds.
PMID- 26422926
TI - [INFLUENCE OF DOXORUBICIN AND ETOPOSIDE ON THE CD 95 MEDIATED APOPTOSIS IN EBV
INFECTED LYMPHOMA CELLS BL-41 AND DG-75].
AB - The aim of work was to study the effect of anticancer drugs on the process of CD
95 mediated apoptosis in BL-41 and DG-75 infected with Epstein-Barr virus.
Studies of the effect of anticancer drugs "Doxorubicin" "Ebewe" and "Vepesid"
(Etoposide) on the apoptosis in EBV infected cells using cytomorphological
methods, spectrophotometry and PCR carried out. The influence of the tested drugs
in cell culture was assessed by calculating the CC50. It was shown that it was 20
MUg ml both for Etoposide and for Doxorubicin in the case of cell line DG-75. BL
41 cells were more sensitive to the tested drugs. CC50 was 5 MUg/mI. PCR method
showed that in the studied cell lines active accumulation of EBV DNA took place.
In 24 hours after infection in the DG 75 + EBV system 20 MUg/ml Doxorubicin
provoked apoptosis in 89% of cells, and Etoposide-induced apoptosis was 35%. Cell
culture BL-41 was equally sensitive to both drugs. At the same time, in the EBV
super infected cells + Doxorubicin only 10% of apoptotic cells were detected. The
obtained data prove the impact of viral infection on the sensitivity of lymphoma
cells BL-41 and DG-75 to tested anticancer drugs.
PMID- 26422927
TI - Retirement Savings Shortfalls: Evidence from EBRI's Retirement Security
Projection Model.
PMID- 26422928
TI - Utilization Patterns and Out-of-Pocket Expenses for Different Health Care
Services Among American Retirees.
PMID- 26422929
TI - Financial Incentives and Workplace Wellness-Program Participation.
PMID- 26422930
TI - The 2015 Retirement Confidence Survey: Having a Retirement Savings Plan a Key
Factor in Americans' Retirement Confidence.
PMID- 26422931
TI - Individual Retirement Account Balances, Contributions, and Rollovers, 2013; With
Longitudinal Results 2010-2013: The EBRI IRA Database.
PMID- 26422932
TI - Health Savings Accounts and Health Reimbursement Arrangements: Assets, Account
Balances, and Rollovers, 2006-2014.
PMID- 26422934
TI - [Can We Avoid the War?].
PMID- 26422933
TI - Intra-Family Cash Transfers in Older American Households.
PMID- 26422935
TI - [Rehabilitation for Pain Relief: Preface and Comments].
AB - Chronic intractable pain is difficult to manage as the mechanisms of chronic pain
are complicated. Recently rehabilitation is used in patients with chronic pain
not responding to NSAIDs, non-opioids, anti-depressants and so on. Rehabilitation
includes acute, recovery and maintained modes of rehabilitation. This review is
focused on the concept of rehabilitation, rehabilitation therapy, rehabilitation
during recovery period, nerve rehabilitation, music-trampoline therapy and so on.
PMID- 26422936
TI - [Basic Strategy for Pain Control in Rehabilitation].
AB - Rehabilitation medicine regards pain as one disorder of whole human character and
handles pain through multilateral approaches. When only the pain is treated it
will not be relieved easily. Chronic pain can be more effectively handled if pain
is considered as one obstacle of the whole human character and handled using many
skills of rehabilitation medicine. We should apply physiotherapy including
functional treatment, physical treatment and exercise from early stages of acute
pain and approach chronic pain. This could improve the effectiveness of treatment
for many kinds of acute pain and chronic pain disorders.
PMID- 26422937
TI - [The Rehabilitation in Pain Clinic].
AB - Rehabilitation is becoming an important field of care at pain clinics designed to
alleviate pain. Exercise and physical therapies are widely used in
rehabilitation, and exercise therapy in particular is considered a treatment that
should be actively incorporated. Intervention must continue to be provided after
ascertaining whether exercise therapy is within the scope of pain clinicians
themselves, or whether it should be offered in collaboration with physical
therapists. This can be achieved by deepening knowledge of exercise therapy and
investigating how it should be offered depending on the disease. Focus should be
placed on abnormal posture and exercise, as well as secondary pain. Visualizing
movement and building up associated sensorimotor experiences are also considered
important. To achieve this, cooperation between physiatrists and physical
therapists, they must deepen and exchange understanding and knowledge with each
other.
PMID- 26422938
TI - [Concept of the Pain Rehabilitation].
AB - Pain causes physical disability and psychosocial issues and consequently reduces
quality of life. Pain rehabilitation with exercise, cognitive-behavioral therapy,
interdisciplinary rehabilitation and patient education improves not only
subjective pain perception but also pain-associated dysfunction. The pain
rehabilitation is characterized by enabling self-management based on patient
centered perspective and decision-making by the patient.
PMID- 26422939
TI - [Rehabilitative Intervention for Low Back Pain].
AB - In the evolution process to a bipedalism animal, human's spinal structure has
been formed by responding to the contradicting functions (firm and flexibility).
Thus, low back pain easily occurs even by a break of extremely slight balance. As
for the cause of the pain, a consistency theory is not established, and we need
to depend on conservative treatment for the treatment And the leading role of the
conservative therapy is rehabilitation. In this report, we introduce scientific
evidence for the effect of the rehabilitative intervention for low back pain.
PMID- 26422940
TI - [Concept of the Pain Management in the Convalescent Rehabilitation].
AB - Convalescent rehabilitation is a treatment designed to facilitate the process of
recovery from disease or injury to as normal a condition as possible. The
effective rehabilitation is required to improve functions to bring about the
highest possible level of independence, physically, psychologically, socially and
economically within a limited hospitalization period. Pain often inhibits the
effective rehabilitation, and the pain management in the convalescent
rehabilitation ward is important. In particular, it is important to evaluate the
pain promptly and accurately, and to treat it by a multidisciplinary team
approach, preventing a shift to chronic pain. In this article, we describe the
role of each member in the convalescent rehabilitation team and the
characteristic pains caused by representative diseases.
PMID- 26422941
TI - [Neurorehabilitation for Neuropathic Pain].
AB - Deafferentation, like as in limb amputation, brachial plexus avulsion injury and
spinal cord injury, is usually followed by neuropathic pain. Neuropathic pain is
a debilitating condition and it impairs the quality of life profoundly. Based on
recent advances in the cognitive neuroscience, we explain intimate relationships
among neuropathic pain, reorganization of primary sensory and motor cortices and
the sensorimotor integration of the deafferentated limb. From the standpoint of
the sensorimotor integration theory for emerging phantom limb pain, we further
discuss the analgesic mechanism of neurorehabilitation techniques such as mirror
visual feedback treatment and its related neurorobotics advancement for
neuropathic pain.
PMID- 26422942
TI - [HRV-Spectral analysis of Pain, by 3D Evaluation and by Balance Index in the Pain
Rehabilitation Field].
AB - Pain signaling is achieved by electrical impulses in the body; however, some
electrical abnormalities can cause pain in the body without generating any
visible symptoms. This phenomenon is sensed by the brain and a signal that may
affect cardiac rhythms is immediately transmitted to the heart. To evaluate heart
rate variability (HRV), the balance correction between an increase and decrease
of heart rate was recorded in real time. Using a special method for spectral
analysis of the HRV, techniques for analyzing the essence of pain were developed,
namely, the 'Balance index' and the '3D spectrum evaluation method'. Using these
techniques, an alpha wave-like factor or a beta wave-like reaction can be
obtained, and the nature and strength of pain can be displayed as spectral zones,
as in a rainbow. The balance reaction can be shown by analyzing data in the
frequency band using a 1/f-like spectral-analysis method. Additionally, emotional
reactions can be detected using a 'Balance index' that can demonstrate imbalance
responding to the pain. The mental state of the subject can also be inferred
because this technique is adapted from the 1/f fluctuation theory related to the
best balanced 1/f-sound wave in nature that comforts the human mind, similar to
music (artificial sound wave). In this study, the variety and intensity of pain
were determined from the frequency band resulting from the 1/f-spectral analysis
of HRV fluctuation. These techniques could explain several situations related to
medication or anesthesia and can be helpful in preventative treatment and/or
explaining the differences in the effectiveness of various techniques for the
rehabilitation of chronic pain.
PMID- 26422943
TI - [Does the Residual Regurgitation on Intraoperative Transesophageal
Echocardiography after Valve Surgery Deteriorate in Early Postoperative Period?].
AB - BACKGROUND: Residual regurgitation after valve surgery affects patients' long
term prognosis. Whether post-repair regurgitation deteriorates postoperatively or
not remains unclear, but this issue is a primary concern of the anesthesiologists
responsible for intraoperative evaluation by transesophageal echocardiography
(TEE). This study was conducted to assess changes in the severity of residual
regurgitation during the early postoperative period. METHODS: Among 160
consecutive patients who underwent valve repair or valve replacement surgery
during April 2010-June 2013 at our institution, 38 (24%) were found to have
residual regurgitation by intraoperative TEE. We retrospectively evaluated these
patients by reviewing follow-up transthoracic echocardiographic examination
records. RESULTS: Residual regurgitation improved in 14 (37%), remained unchanged
in 21 (55%), and worse in 3 (8%). All three patients showing worse regurgitation
had undergone valve repair. Of them, one had reoperation one year later. No
worsening of regurgitation, including perivalvular leakage, was found in patients
who had undergone valve replacement. CONCLUSIONS: In valve repair, even mild
residual regurgitation deteriorates postoperatively. Therefore, it should be
observed cautiously. In valve replacement mild residual regurgitation did not
deteriorate, irrespective of the regurgitation mechanism.
PMID- 26422944
TI - [Levobupivacaine for Ultrasound-guided Interscalene Block: Block with 6 ml Leads
to Less Occurrence of Respiratory Depression and Hemidiaphragmatic Paralysis].
AB - BACKGROUND: Interscalene brachial plexus block (ISBPB) complications depend
usually on the dose administered. METHODS: The object of this study was to
determine whether ultrasound-guided ISBPB with 6 ml of 0.5% levobupivacaine would
reduce occurrence of respiratory depression and hemidiaphragmatic paralysis.
RESULTS: Patients undergoing arthroscopic shoulder surgery under nerve block with
general anesthesia (n = 20) were recruited. There were no differences between pre
and post operative respiratory function (forced expiratory volume 1.0 (sec) % and
vital capacity). Hemidiaphragmatic paralysis on postoperative ultrasonography was
found in two patients. CONCLUSIONS: The use of low-volume ultrasound-guided ISBPB
is associated with less respiratory depression and hemidiaphragmatic paralysis.
PMID- 26422945
TI - [A Case of Mitral Valvular Re-repair in a Patient with Hemolytic Anemia after
Mitral Valvular Repair].
AB - A 54-year-old woman was admitted for mitral valvular repair. After folding plasty
to A3, a 30 mm Cosgrove-Edwards ring was placed. There was no mitral
regurgitation jet observed by transesophageal echocardiography (TEE) during the
operation. However, high blood pressure was monitored and treated in the
intensive care unit, hemolytic anemia developed, and the serum lactate
dehydrogenase level was elevated. Two weeks after the operation, serum lactate
dehydrogenase was again elevated. TEE showed mild mitral regurgitation and the
regurgitation jet colliding with the annuloplasty ring. Multiple transfusions of
red blood cells were required. Repeat surgery was therefore undertaken. Lam and
associates previously studying patients on hemolysis after mitral valvular repair
noted high grade mitral regurgitation jets fragmented or accelerated. In the
present case, mitral regurgitation was mild, but the high velocity and manner of
regurgitation (collision with the annuloplasty ring) could cause hemolytic
anemia. In the present case, high blood pressure might have caused chordae
rupture. Furthermore, a flexible ring, such as the Cosgrove-Edwards ring, is
likely to cause hemolytic anemia. As contributing factors to hemolysis after
mitral valvular repair, perioperative blood pressure management and type of ring
are significant.
PMID- 26422946
TI - [Anesthetic Management of a Patient with Quasi-moyamoya Disease Undergoing Total
Thyroidectomy for Graves' Disease].
AB - Quasi-moyamoya disease defined as moyamoya disease combined with autoimmune
diseases such as Graves' disease is rare. We report anesthetic management of a
patient with quasi-moyamoya disease undergoing total thyroidectomy for Graves'
disease resistant to medical therapy. This disease is characterized by the
aggravation of cerebral ischemic symptoms with hyperthyroidism. We, therefore,
applied steroid pulse therapy before the operation to induce temporal
normalization of the thyroid function, and could perform safe anesthetic
management of this patient with quasi-moyamoya disease.
PMID- 26422948
TI - [The SorbaView SHIELD is a Useful Product for Use in Perioperative Management].
AB - BACKGROUND: We studied the stability of the continuous arterial pressure line (A
line) achieved by using a catheter securement device. METHODS: A total of 100
patients requiring an arterial catheter were divided into 2 groups of fixation:
(1) fixation achieved by using the SorbaView SHIELD (Centurion Medical Products
Corporation, USA) and (2) fixation by using Tegaderm 3 M (TEGADERM 3 M, Japan).
We analyzed the stability of the fixation, presence or absence of skin disorders,
and the preference by nurses. RESULTS: The SorbaView SHIELD was superior judged
by nurses and was found to render more stability to the fixation of the A line as
compared to Tegaderm 3 M, especially when transferring a patient into the
intensive care unit after surgery. CONCLUSIONS: We conclude that stability of the
A line maintained by the use of the SorbaView SHIELD is more effective in
maintaining the stability of the A line.
PMID- 26422947
TI - [Simulation-based Perioperative Team Training in the Operating Room].
AB - Here, we report the development of a simulation-based perioperative training
course. Participants were anesthesiologists and operating room nurses. Three
different courses were held with different themes, such as airway management,
circulation management and central venous management. The courses included a
lecture and simulation training with scenario-based discussions or a simulator.
At the end of each course, participants discussed problems associated with
medical safety in the context of each theme. Participants commented not only on
changes in their views regarding individual technical or non-technical
improvements, but also on general medical safety in the operating room. Our
findings suggest that simulation-based perioperative team training may serve as a
vehicle to promote operating room safety.
PMID- 26422949
TI - [Did Seikyo Sugita Perform Two Surgical Operations under Ether Anesthesia in
1855?].
AB - Although Seikyou Sugita is said to have provided ether anesthesia for two
surgical oprations in 1855 including the scur resection of burned fingers of a
man and the resection of a breast cancer of a woman. The details of his
administration of the drug were not known because he did not describe these cases
at all. According to Treatise on Inhalation of Ether written in 1863 by Shinryo
Tsuboi, Sugita failed to provide successful general anesthesia using ether for
these patients. The ether he used was prepared by Ryuho Shima, and the failures
were likely to be due to impure nature of the agent.
PMID- 26422950
TI - [Several Issues before and after the Recognition of "Anesthesiology" as
"Specially Approved Specialty"].
AB - A movement occurred at the end of 1940's among members of the Japan Medical
Association (JMA) to recognize "specially approved specialty" in the practice of
medicine, but their petition was rejected by the Medical Ethics Committee. Thus,
the JMA expanded an energetic campaign for the recognition, by the support from
four diet members. Consequently, six specialties including neurology and
venereology were eventually accredited as "generally approved specialty" in 1950.
About 1960, several years after anesthesiology having been recognized as a
"specially approved medical specialty", some elder members of the Japan Society
of Anesthesiology (JSA) discussed to change the term "specially approved
specialty" to "generally approved medical specialty"in the Medical Service Law,
but their motion could not gain majority support at the Councils of Elders of the
JSA. The council also presented to the Ministry of Health and Welfare (MHW), a
written request to alter the eligibility criteria of a registered
anesthesiologist; however, the request was declined because of a strong
opposition of the MHW which was under the strong influence of the JMA. The JSA
did never show interest to these issues since then, and the situation remains
unchanged to the present.
PMID- 26422951
TI - [My Personal Opinion Facing the Gender Equality Society].
PMID- 26422952
TI - [Intraoperative Neurological Monitoring from the Anesthesiologist's Point of View
Preface and Comments].
AB - Intraoperative neurophysiological monitoring has been increasingly utilized for
many neurosurgical procedures as well as for spine and aortic surgery. The recent
advances in monitoring devices and anesthesia techniques have improved the
reliability and accuracy of intraoperative neurological monitoring. In this
issue, we review the basic principle, methods, and clinical application of
several modalities of neurological monitoring to detect neural tissue ischemia
and the direct physical injury to the specific neural pathway during surgical
procedures. These modalities include near-infrared spectroscopy, motor evoked
potentials, somatosensory evoked potentials, auditory brainstem responses, and
visual evoked potentials. Pitfalls and limitations of each modality are also
discussed. Evidence for the efficacy of the monitoring varied with surgical
procedures, but has been well validated in some procedures. Anesthesiologists can
contribute to the reliability and efficacy of neurophysiological monitoring by
maintaining good physiological homeostasis and stable levels of anesthesia during
the surgical procedure. With appropriate knowledge and experience, the
anesthesiologist should work together with the neuromonitoring staff and surgeon
to ensure neurological safety for the patient during and after surgery.
PMID- 26422953
TI - [Validity of Near-infrared Spectroscopy].
AB - Regional cerebral oxygen saturation measured by near-infrared spectroscopy has
been used clinically. Its usefulness in cardiac surgery and neurosurgery was also
reported. On the other hand, accuracy of rSO2 values has been supposed to be
doubtful due to extra-cerebral contamination and unstable mean optical path
length. Therefore, we tried to review issues for accuracy of rSO2 values and
clinical usefulness. Our aim is to clarify the issue and clinical usefulness of
measuring regional cerebral oxygen saturation.
PMID- 26422954
TI - [Somatosensory Evoked Potential during Cardiac Surgery].
AB - Neurologic complications are common in cardiac surgery. The rate of complication
can range from 1.6% to 23% for permanent neurologic deficits and from 7% to 61%
for transient neurologic deficits. Although several studies have suggested the
effectiveness of brain monitoring in reducing postoperative adverse neurologic
outcomes, brain monitoring during cardiac surgery has not yet been adopted for
routine use. Somatosensory evoked potential (SEP) can provide direct information
on the integrity of somatosensory pathway such as SEP elicited by median nerve
stimulation in cardiac surgery. An electrode is placed over primary sensory
cortex, C3' C4', so called Shagss point. The N20/P25 waveform can be recorded.
N20/P25 evoked potentials reflect the perfusion of medial brain circulation. When
cerebral blood flow decreases or when brachial plexus is obstructed, N20/P25
amplitude decreases with latency delay. SEP can quickly detect brain ischemia and
brachial plexus dysfunction, and it is useful for nervous system monitoring in
cardiac surgery.
PMID- 26422955
TI - [Motor Evoked Potentials and Aortic Surgery].
AB - Motor dysfunction following descending and thoracoabdominal aortic surgery
including thoracic endovascular aortic repair remains as one of their devastating
complications, although several interventions have tried to preserve spinal cord
blood flow during and after aortic aneurysm surgery for the purpose of reducing
the incidence of postoperative paraplegia. One of the main limitations of
protective strategies is the inability to assess the adequacy of spinal cord
perfusion and spinal cord function intraoperatively. Advances in stimulation
technique using short train pulses could make intraoperative monitoring of
functional integrity of motor pathways possible by recording myogenic motor
evoked potentials (MEP), which is a highly sensitive technique to assess spinal
cord integrity, identifying insufficient blood flow. To reduce the risk of
neurologic injury, anesthesiologists are required to properly understand
monitoring of MEP and to manage anesthesia and hemodynamics appropriately. Here,
we summarize the strategies for spinal cord protection, including the functional
monitoring of spinal cord and anesthetic techniques.
PMID- 26422956
TI - [Intraoperative Electrophysiological Monitoring for Neurosurgery].
AB - Both motor evoked potential (MEP) and somatosensory evoked potential (SEP) have
been used for the purpose of preventing postoperative neurological complications
in patients undergoing neurosurgery. Although not completely, they can detect
insufficient cerebral blood flow during aneurysm surgery and carotid surgery and
prevent functional deterioration during tumor resection. Regarding MEP, there are
several points to be considered for maximizing the potential of MEP. First,
suprathreshold stimulus should be used because supramaximal stimulus may be too
strong, resulting in false negative responses. Second, direct cortical
stimulation in addition to transcranial stimulation may be useful for stimulating
the target area precisely. Third, subcortical stimulation can provide decisive
information during tumor resection. Although there is no such thing as 100%
accuracy in electrophysiological monitoring, a multimodal electrophysiological
monitoring system may contribute to decrease neurological deficits. Irreversible
neurological deficits could be prevented by early detection of the changes in the
amplitude and by prompt intervention to correct deteriorating condition.
Therefore, it is important for anesthesiologists to select suitable anesthetics
for the monitoring, maintain the depth of anesthesia, and discuss the patient
management with surgeons.
PMID- 26422957
TI - [Intraoperative ABR Monitoring in Neurosurgery].
AB - Monitoring of the intraoperative auditory brainstem response (ABR) is a less
invasive, easy, and useful method for hearing preservation in patient undergoing
cerebellopontine angle surgery such as microvascular decompression (MVD) and
excision of an acoustic neurinoma. The ABR is tolerant of both inhalation and
intravenous anesthesia. However, ABR recordings are highly susceptible to
electrical noise from surgical devices. Therefore, for ABR recordings to be
reliable, noise must be minimized and appropriate evaluation of waveform changes
is critical. Electrode setting with low contact impedance and bilateral
derivation effectively address these issues. Prolongation of the wave V latency
alerts to surgical stress on the cochlear nerve due to nerve stretching from
cerebellar retraction. According to Sekiya, the surgeon performing MVD or
acoustic neurinoma excision should be warned as soon as latency prolongation
exceeds 1.5 msec or characteristics of ABR must be understood. even less than 0.5
msec, respectively. However, hearing was preserved in some patients with false
positive results with respect to intraoperative wave V diminution. To use it as a
useful intraoperative modality, the Characteristics of ABR must be understood.
PMID- 26422958
TI - [Intraoperative Visual Evoked Potential Monitoring].
AB - Visual evoked potential (VEP) is recorded from the back of the head, which is
elicited by retinal stimulation transmitted through optic nerve, optic chiasm,
optic tract lateral geniculate body, optic radiation and finally cortical visual
area. VEP monitoring did not prevail since 1990s because marked intra-individual
difference and instability of VEP recording limited the clinical usefulness under
inhalation anesthetic management and techniques of VEP monitoring at the time.
However, recent advances in techniques including a new light-stimulating device
consisting of high-luminosity LEDs and induction of electroretinography to
ascertain the arrival of the stimulus at the retina provided better conditions
for stable VEP recording under general anesthesia. In addition, the introduction
of total intravenous anesthesia using propofol is important for the successful
VEP recordings because inhaled anesthetics have suppressive effect on VEP
waveform. Intraoperative VEP has been considered to monitor the functional
integrity of visual function during neurosurgical procedures, in which the optic
pathway is at a risk of injury. Intraoperative VEP monitoring may allow us to
detect reversible damage to the visual pathway intraoperatively and enable us to
prevent permanent impairment.
PMID- 26422959
TI - [Motor Evoked Potential and Somatosensory Evoked Potential during Spine and
Spinal Surgery].
AB - Spine and spinal cord surgery carries a significant risk of neurological
impairment Intraoperative neurological monitoring should now include not only
somatosensory evoked potential (SEP), but also motor evoked potential (MEP).
While SEP monitors the posterior cord, MEP provides better information regarding
the status of the anterior/anterolateral cord. The multimodality SEP and MEP
monitoring essentially covers physiological changes of the entire cord, and
thereby reduces the risk of development of irreversible neural injury. A 50% drop
in SEP amplitude is the universally accepted warning criteria. Conversely,
different warning criteria for MEP have been proposed because of MEP especially
sensitive to the effects of anesthetic agents. Although evidence lacks that
intraoperative evoked potential reduces the rate of neurologic deficits, it is
recommended to monitor MEP for spine and spinal surgery, when the spinal cord is
considered to be at risk. The anesthesiologist must be familiar with SEP and MEP
monitoring to increase the preciseness of the monitoring.
PMID- 26422960
TI - [Spontaneous Respiration Technique for Pediatric Microlaryngeal Surgery without
Endotracheal Intubation].
AB - We report the anesthetic management of microlaryngeal surgery in children using
tubeless total intravenous anesthesia (TIVA) without endotracheal intubation
under spontaneous breathing. In 9 patients (median age : 4.9 yr. range 1 months
14 years, body weight : 17 kg, range 3-61 kg), 19 procedures were performed with
TIVA using propofol and remifentanil. The median time from the start of TIVA to
rigid laryngoscope insertion was 11 minutes. Propofol 15.7 mg x kg(-1) x hr(-1)
and remifentanil 0.05 MUg x kg(-1) x min(-1) was infused in this interval.
Laryngospasm was observed in two cases, but it responded to a bolus of propofol
(0.5-1.0 mg x kg(-1)) and additional topical anesthesia with 1% lidocaine. Three
children were found apneic after a bolus administration of remifentanil or after
increasing the rate of remifentanil infusion accompanied with desaturation and
their tracheae were intubated. The spontaneous respiration technique using TIVA
without intubation provides an excellent view of the operative field while
allowing stable anesthesia. Further studies are required to establish the optimal
dose of propofol and remifentanil and the timing of rigid laryngoscope insertion.
PMID- 26422961
TI - [Anesthetic Management of Right Lower Lobectomy in a Patient with Marfan
Syndrome].
AB - We report a case of partial lobectomy in a patient with Marfan syndrome. A 56
year-old woman with Marfan syndrome was scheduled for partial lobectomy for
suspected lung cancer under general anesthesia. She underwent a Bentall operation
and mitral valve replacement 10 months before and strict blood pressure
management was required. After induction of general anesthesia with propofol and
fentanyl, topical intratracheal lidocaine anesthesia was performed using the
Pentax-AWS Airwayscope (AWS) for visualization, allowing for the Soft-tipped Tube
Exchanger (TE-Soft) to be inserted into the trachea. Next, a double-lumen
tracheal tube was uneventfully intubated via the TE-Soft with minimal change in
vital signs. During the operation, pressure-controlled ventilation was performed
to minimize the risk of pneumothorax. After the operation, under continuous
administration of landiorol and dexmedetomidine, the double-lumen tracheal tube
was extubated uneventfully. Strict airway and circulation management is needed
for lung or vessel preservation in patients whose conditions are complicated by
Marfan syndrome.
PMID- 26422962
TI - [Tracheal Intubation via the i-gel and the Aintree Intubation Catheter in a
Patient with Unexpected Difficult Intubation].
AB - A 64-year-old man was scheduled for radical sinus operation. Preoperatively, we
did not expect difficult airway. We induced general anesthesia, and ventilation
via facemask was adequate, but tracheal intubation using a Macintosh laryngoscope
was difficult (Cormack-Lehane classification III). We inserted the i-gel, and a
fiberoptic bronchoscope covered with the Aintree Intubation Catheter (AIC), was
passed through the i-gel to the trachea. We removed i-gel and fiberscope, leaving
the AIC in place, and could easily advance a reinforced tube over the AIC into
the trachea. Fiberoptic tracheal intubation via the i-gel and AIC is useful in a
patient with difficult intubation.
PMID- 26422963
TI - [Lateral Approach Tracheal Intubation in a Semi-sitting Position Utilizing a
Videolaryngoscope in a Patient with Respiratory Failure due to Septic Shock].
AB - Here we report our success in performing lateral approach tracheal intubation in
a patient with severe respiratory failure due to septic shock caused by shoulder
joint abscess. A 71-year-old woman presented with severe respiratory difficulty
due to sepsis from a shoulder joint abscess and was scheduled for emergent
drainage and irrigation. She could not breathe sufficiently in the supine
position and thus maintained a semi-sitting position. She was also unable to move
from the ward bed to the operating table due to severe shoulder pain. We induced
anesthesia in a semi-sitting position in the ward bed. Mask ventilation was
performed using the two-hand technique from the lateral approach. Tracheal
intubation was also performed with a left lateral approach utilizing the Pentax
AWS Airwayscope (AWS). Lateral approach for tracheal intubation utilizing AWS may
be useful in patients who present with severe respiratory difficulty.
PMID- 26422964
TI - [Ossification of the Posterior Longitudinal Ligament Found in a Case of Sudden
Head-tilt Difficulty following Induction of General Anesthesia].
AB - We report a case of sudden head-tilt difficulty after induction of general
anesthesia which was postoperatively diagnosed as ossification of the posterior
longitudinal ligament. A 42-year-old man weighing 115 kg was scheduled for
emergent laparoscopic appendectomy for acute appendicitis. Prior to induction of
anesthesia, the patient could tilt his head, but was unable to do so afterwards.
Following mask ventilation with jaw-thrust maneuver, we successfully performed
tracheal intubation using the Pentax-AWS Airwayscope. After surgery, he was
diagnosed with ossification of the posterior longitudinal ligament by an
orthopedist.
PMID- 26422965
TI - [Successful Airway Management Using the air-Q Intubating Laryngeal Airway under
Dexmedetomidine and Laryngeus Superior Nerve Block for Severe Tracheal Stenosis
due to Thyroid Cancer Invasion].
AB - A 75-year-old woman suffering from respiratory difficulty was diagnosed with
severe tracheal stenosis due o malignant thyroid cancer. She was scheduled for an
mergent tracheotomy, but preoperative computed omography revealed severe tracheal
stenosis below he glottis due to thyroid cancer invasion. Anticipating lifficult
tracheal intubation and risk of obstruction from hemorrhage, intubation
preserving spontaneous ventiation was performed to avoid a 'can't ventilate,
can't intubate' situation. A size 3.5 air-Q intubating laryngeal airway was
inserted using a bronchofiberscope to perform tracheal intubation in a semi
sitting position. Successful tracheal intubation which avoided damage to the
tumor was achieved while maintaining spontaneous ventilation. The air-Q
intubating laryngeal airway was useful in this setting of severe tracheal
stenosis due to thyroid cancer just under the glottis.
PMID- 26422966
TI - [Anesthetic Management of a Patient for Total Gastrectomy after Coronary Artery
Bypass Grafting Using the Right Gastroepiploic Artery].
AB - We report anesthetic management of total gastrectomy for gastric cancer under
general anesthesia supplemented with a transversus abdominis plane (TAP) block.
The patient was a 78-year-old man who had received coronary artery bypass
grafting (CABG) with the right gastroepiploic artery (RGEA) 12 years before.
Preoperative coronary angiography (CAG) showed that RCA was obstructed completely
and RGEA was patent and the surgeons carried out gastrectomy with the utmost
attention not to injure the RGEA. There were no signs of myocardial ischemia
under monitoring by transesophageal echocardiography (TEE). The ultrasound-guided
TAP block was effective. This case demonstrates that the ultrasound-guided TAP
block is an alternative approach for providing analgesia and intraoperative TEE
monitoring is useful in a patient with gastrectomy after CABG using the RGEA with
coagulation abnormality.
PMID- 26422967
TI - [Anesthetic Management Using Frontal Nerve, Greater Occipital Nerve, and
Superficial Cervical Plexus Block for Posterior Cervical Spinal Fusion in a
Patient with Athetoid Cerebral Palsy].
AB - Here, we report successful anesthetic management of posterior cervical spinal
fusion utilizing block of the frontal nerve, the greater occipital nerve, and the
superficial cervical plexus in a patient with athetoid cerebral palsy. A 69-year
old woman (height 157 cm; weight 33 kg) with athetoid cerebral palsy was
scheduled to undergo posterior cervical spinal fusion for cervical spondylotic
myelopathy. After induction of general anesthesia, we performed tracheal
intubation using the Pentax-AWS Airwayscope with a thin Intlock. After tracheal
intubation, we used ropivacaine for the frontal nerve, greater occipital nerve,
and superficial cervical plexus block. Anesthetic maintenance was performed with
total intravenous anesthesia utilizing propofol and remifentanil. Continuous
administration of dexmedetomidine was started during operation. Following
surgery, smooth spontaneous ventilation was observed following uneventful
extubation. No significant pain and no athetoid movement were observed under
continuous administration of dexmedetomidine.
PMID- 26422968
TI - [A Case of Severe Bradycardia Associated with Bladder Perforation during Spinal
Anesthesia].
AB - Here we report a case of severe bradycardia associated with bladder perforation
during transurethral resection of the bladder. The patient was diagnosed with
bladder cancer eight months ago and underwent transurethral resection of the
bladder tumor. After balloon-occluded arterial infusion chemotherapy, she was
scheduled for a bladder biopsy under spinal anesthesia. Spinal anesthesia was
induced with 2.5 ml of 0.5% bupivacaine hydrochloride at L3-4, and sensory loss
(T9) was confirmed. The operation started uneventfully 20 minutes after
bupivacaine administration. However, ten minutes into the operation, bladder
perforation occurred and was followed by severe bradycardia (20-30 beats x min(
1)). While preparing for transcutaneous pacing, bradycardia improved with
intravenous atropine and ephedrine. The level of spinal anesthesia remained
unchanged. General anesthesia was induced with propofol, rocuronium and fentanyl.
The patient was extubated uneventfully after the operation and was discharged 14
days later.
PMID- 26422969
TI - [A Problem with Flow Indicators of Anesthesia Machine].
AB - Some anesthesia machines indicate both analog and digital flow volumes of oxygen,
air and nitrous oxide. We have noticed that there are discrepancies in the flows
between analog and digital flow indicators of two anesthesia machine models
(Drager ; Fabius GS premium and Fabius Tiro). When oxygen or air flow is low, the
analog indicator shows higher flows than the digital indicator. In contrast, when
oxygen or air flow is high, the analog indicator shows lower flows than the
digital indicator. This discrepancy is comparatively small when total gas flow is
within the range of 2-5 l x min(-1). We contacted the manufacturer, which replied
that the digital indicator is correct and the analog indicator should be regarded
as an adjunctive, in case of a power failure when the digital indicator does not
function. But this discrepancy may cause practical problems. When we cannot use a
digital indicator and have to perform ventilation using a supporting gas
cylinder, we may misjudge the available time for oxygen. In addition, when we use
only analog indicator, insufficient volume of oxygen may be delivered, leading to
the grave hypoxia.
PMID- 26422970
TI - [Video Laryngoscopy Reduces the Incidence of Erroneous Esophageal Intubation: A
Meta-analysis].
AB - BACKGROUND: The aim of this meta-analysis is to compare the incidence of
erroneous esophageal intubations by video laryngoscopy to that by direct
laryngoscopy. METHODS: The systematic search, data extraction, critical
appraisal, and pooled analysis were performed according the PRISMA statement. The
odds ratio(OR) and 95% confidence interval (CI) were calculated by the Review
Manager 5.2 software for dichotomous outcome. RESULTS: Eleven trials included
1425 tracheal intubations by video laryngoscopy and 1632 tracheal intubations by
Macintosh laryngoscopy. Video laryngoscopy reduced the risk of erroneous
esophageal intubations (OR 0.10, 95% CI 0.04-0.24, P < 0.00001, I2 : 0%) compared
with Macintosh laryngoscopy. CONCLUSIONS: Our meta-analysis showed that video
laryngoscopy would reduce the incidence of erroneous esophageal intubations.
PMID- 26422971
TI - [Development and Hosting of a Perioperative Advanced Life Support Training Course
for Anesthesiologists].
AB - Participation in the American Heart Association advanced cardiac life support
provider course is a prerequisite for taking the anesthesiology specialist
examination in Japan. The course teaches fundamental resuscitation methods for
different types of cardiac arrest. However, crisis in the perioperative period
can result from airway trouble, central venous catheter displacement, or massive
hemorrhage. We report our experience of holding a problem- and learning-based
perioperative advanced life support training course, Advanced Life Support for
Operation (ALS-OP). Main contents of the course included circulation management,
airway management central venous catheters, and pain clinic-related
complications. ALS-OP simulation training may be beneficial for educating
anesthesiologist and promoting perioperative patient safety.
PMID- 26422972
TI - [Laryngeal Tube Position Shift after Chest Compression: Comparison of Fixation
Methods Using Durapore Tape, Multipore Tape, or a Neck Tape].
AB - BACKGROUND: The laryngeal tube (LT ; Smiths Medical, Minnesota, U. S. A) is an
inflatable supraglottic device for emergency airway management such as during
chest compression, the instability after insertion remains a problem. METHODS: We
investigated the effectiveness of three fixation methods of LT using a manikin
and automated chest compressor. RESULTS: After 10-minute chest compression, LT
without fixation was shifted by 0.4 +/- 0.1 cm, which was greater than with
Durapore tape (0.2 +/- 0.1 cm), Multipore tape (0.2 +/- 0.1 cm), or a neck tape
(0.1 +/- 0.1 cm). The shift of the position was smaller with neck tape fixation
compared to Durapore or Multipore tape fixation. CONCLUSIONS: A fixation neck
tape may be useful in stabilizing the inserted position of LT during
cardiopulmonary resuscitation.
PMID- 26422973
TI - Primary pancreatic Hodgkin's lymphoma diagnosed on EUS-guided FNA.
PMID- 26422974
TI - A knotty problem.
PMID- 26422975
TI - Mirizzi's syndrome presenting after laparoscopic cholecystectomy.
PMID- 26422976
TI - Rendezvous procedure at 6 weeks of age.
PMID- 26422977
TI - Sodium polystyrene sulfonate-induced esophageal ulcer.
PMID- 26422978
TI - A case of extramedullary involvement of acute monocytic leukemia that presented
as obstructive jaundice.
PMID- 26422979
TI - Diagnostic yield of EUS-guided FNA for malignant biliary stricture: a systematic
review and meta-analysis.
AB - BACKGROUND AND AIMS: EUS-guided FNA (EUS-FNA) is increasingly being used for
tissue diagnosis of extrahepatic biliary strictures. The aim of this study was to
determine the diagnostic yield of EUS-FNA in malignant biliary strictures.
METHODS: A comprehensive literature review was carried out by 2 reviewers for
studies evaluating the accuracy of EUS-FNA in biliary stricture. A meta-analysis
was performed to determine the pooled estimates of sensitivity, specificity,
likelihood ratios, and diagnostic odds ratio for EUS-FNA of extrahepatic biliary
stricture. A Quality Assessment of Diagnostic Accuracy Studies questionnaire was
used to assess the quality of the selected studies. Several sensitivity analyses
were performed to assess the effect of the quality of the studies on the accuracy
of the final results of the meta-analysis. RESULTS: Twenty studies involving 957
patients met inclusion criteria and were included in the meta-analysis. The
pooled sensitivity and specificity of EUS-FNA for diagnosis of malignant biliary
stricture were 80% (95% confidence interval [CI], 74%-86%), and 97% (95% CI, 94%
99%), respectively. The pooled positive likelihood ratio was 12.35 (95% CI, 7.37
20.72), and the negative likelihood ratio was 0.26 (95% CI, 0.18-0.38). The
pooled diagnostic odds ratio for diagnosing a malignant biliary stricture was
70.53 (95% CI, 38.62-128.82). The area under the receiver-operating
characteristic curve was 0.97. Sensitivity analyses showed that the quality of
the included studies did not affect the accuracy of the final results of the meta
analysis. CONCLUSION: This meta-analysis demonstrates that EUS-FNA is sensitive
and highly specific for diagnosing malignancy in biliary strictures. Further
studies are needed to compare EUS--FNA with emerging methods including
cholangioscopy-guided biopsy and laser endomicroscopy.
PMID- 26422981
TI - Unifying Mechanism of Controlling Kir3 Channel Activity by G Proteins and
Phosphoinositides.
AB - The question that started with the pioneering work of Otto Loewi in the 1920s, to
identify how stimulation of the vagus nerve decreased heart rate, is approaching
its 100th year anniversary. In the meantime, we have learned that the
neurotransmitter acetylcholine acting through muscarinic M2 receptors activates
cardiac potassium (Kir3) channels via the betagamma subunits of G proteins, an
important effect that contributes to slowing atrial pacemaker activity.
Concurrent stimulation of M1 or M3 receptors hydrolyzes PIP2, a signaling
phospholipid essential to maintaining Kir3 channel activity, thus causing
desensitization of channel activity and protecting the heart from overinhibition
of pacemaker activity. Four mammalian members of the Kir3 subfamily, expressed in
heart, brain, endocrine organs, etc., are modulated by a plethora of stimuli to
regulate cellular excitability. With the recent great advances in ion channel
structural biology, three-dimensional structures of Kir3 channels with PIP2 and
the Gbetagamma subunits are now available. Mechanistic insights have emerged that
explain how modulatory control of activity feeds into a core mechanism of channel
PIP2 interactions to regulate the conformation of channel gates. This complex but
beautiful system continues to surprise us for almost 100 years with an apparent
wisdom in its intricate design.
PMID- 26422980
TI - Double-blind randomised controlled trial of percutaneous tibial nerve stimulation
versus sham electrical stimulation in the treatment of faecal incontinence:
CONtrol of Faecal Incontinence using Distal NeuromodulaTion (the CONFIDeNT
trial).
AB - BACKGROUND: Faecal incontinence (FI) is a common condition which is often under
reported. It is distressing for those suffering from it, impacting heavily on
their quality of life. When conservative strategies fail, treatment options are
limited. Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive
outpatient treatment, shown in preliminary case series to have significant
effectiveness; however, no randomised controlled trial has been conducted.
OBJECTIVES: To assess the effectiveness of PTNS compared with sham electrical
stimulation in the treatment of patients with FI in whom initial conservative
strategies have failed. DESIGN: Multicentre, parallel-arm, double-blind
randomised (1 : 1) controlled trial. SETTING: Eighteen UK centres providing
specialist nurse-led (or equivalent) treatment for pelvic floor disorders.
PARTICIPANTS: Participants aged > 18 years with FI who have failed conservative
treatments and whose symptoms are sufficiently severe to merit further
intervention. INTERVENTIONS: PTNS was delivered via the Urgent((r)) PC device
(Uroplasty Limited, Manchester, UK), a hand-held pulse generator unit, with
single-use leads and fine-needle electrodes. The needle was inserted near the
tibial nerve on the right leg adhering to the manufacturer's protocol (and
specialist training). Treatment was for 30 minutes weekly for a duration of 12
treatments. Validated sham stimulation involved insertion of the Urgent PC needle
subcutaneously at the same site with electrical stimulation delivered to the
distal foot using transcutaneous electrical nerve stimulation. MAIN OUTCOME
MEASURES: Outcome measures were assessed at baseline and 2 weeks following
treatment. Clinical outcomes were derived from bowel diaries and validated,
investigator-administered questionnaires. The primary outcome classified patients
as responders or non-responders, with a responder defined as someone having
achieved >= 50% reduction in weekly faecal incontinence episodes (FIEs). RESULTS:
In total, 227 patients were randomised from 373 screened: 115 received PTNS and
112 received sham stimulation. There were 12 trial withdrawals: seven from the
PTNS arm and five from the sham arm. Missing data were multiply imputed. For the
primary outcome, the proportion of patients achieving a >= 50% reduction in
weekly FIEs was similar in both arms: 39 in the PTNS arm (38%) compared with 32
in the sham arm (31%) [odds ratio 1.28, 95% confidence interval (CI) 0.72 to
2.28; p = 0.396]. For the secondary outcomes, significantly greater decreases in
weekly FIEs were observed in the PTNS arm than in the sham arm (beta -2.3, 95% CI
-4.2 to -0.3; p = 0.02), comprising a reduction in urge FIEs (p = 0.02) rather
than passive FIEs (p = 0.23). No significant differences were found in the St
Mark's Continence Score or any quality-of-life measures. No serious adverse
events related to treatment were reported. CONCLUSIONS: PTNS did not show
significant clinical benefit over sham electrical stimulation in the treatment of
FI based on number of patients who received at least a 50% reduction in weekly
FIE. It would be difficult to recommend this therapy for the patient population
studied. Further research will concentrate on particular subgroups of patients,
for example those with pure urge FI. TRIAL REGISTRATION: Current Controlled
Trials ISRCTN88559475. FUNDING: This project was funded by the NIHR Health
Technology Assessment programme and will be published in full in Health
Technology Assessment; Vol. 19, No. 77. See the NIHR Journals Library website for
further project information.
PMID- 26422982
TI - The Roles of Gbetagamma and Galpha in Gating and Regulation of GIRK Channels.
AB - G protein-gated K(+) (GIRK, or Kir3) channels mediate inhibitory
neurotransmission via G protein-coupled receptors (GPCRs) in heart and brain. The
signaling cascade involves activation of GPCR by an agonist, activation of a G
protein followed by rearrangement or dissociation of activated Galpha(GTP) from
Gbetagamma, and activation of GIRK by Gbetagamma. Gbetagamma is the main
transducer of GPCR activating signal to the GIRK channel. It promotes channel
opening by direct binding to GIRK's cytosolic domain formed by the N- and C
terminal segments of the GIRK's four subunits. Gbetagamma's interaction with, and
activation of, the GIRK channels are well understood and reviewed elsewhere;
however, several important details involving distal parts of the cytosolic domain
remain incompletely understood. Galpha(i/o) also binds to GIRKs and has been
implicated in regulating channel's gating, in concert with Gbetagamma. Among
known functions of Galpha, best-described (though not well understood) are
selectivity of signaling (only G(i/o) proteins normally couple to GIRKs) and
regulation of the basal activity of GIRKs (I(basal)). A role for a direct effect
of the activated Galpha(i/o)(GTP) in GIRK gating has also been proposed but
remains elusive. This chapter discusses the mechanisms of signaling within the
essential cascade, from GPCR to the heterotrimeric G protein and to the channel.
The focus is on the role of Galpha and on the relationships between Galpha and
Gbetagamma in channel regulation, their role in specific signaling from GPCRs to
GIRKs, and the role of stoichiometry and cooperativity of G protein-GIRK
interactions in channel's function.
PMID- 26422983
TI - RGS Redundancy and Implications in GPCR-GIRK Signaling.
AB - Regulators of G protein signaling (RGS proteins) are key components of GPCR
complexes, interacting directly with G protein alpha-subunits to enhance their
intrinsic GTPase activity. The functional consequence is an accelerated
termination of G protein effectors including certain ion channels. RGS proteins
have a profound impact on the membrane-delimited gating behavior of G-protein
activated inwardly rectifying K(+) (GIRK) channels as demonstrated in
reconstitution assays and recent RGS knockout mice studies. Akin to GPCRs and G
protein alphabetagamma subunits, multiple RGS isoforms are expressed within
single GIRK-expressing neurons, suggesting functional redundancy and/or
specificity in GPCR-GIRK channel signaling. The extent and impact of RGS
redundancy in neuronal GPCR-GIRK channel signaling is currently not fully
appreciated; however, recent studies from RGS knockout mice are providing
important new clues on the impact of individual endogenous RGS proteins and the
extent of RGS functional redundancy. Incorporating "tools" such as engineered RGS
resistant Galphai/o subunits provide an important assessment method for
determining the impact of all endogenous RGS proteins on a given GPCR response
and an accounting benchmark to assess the impact of individual RGS knockouts on
overall RGS redundancy within a given neuron. Elucidating the degree of
regulation attributable to specific RGS proteins in GIRK channel function will
aid in the assessment of individual RGS proteins as viable therapeutic targets in
epilepsy, ataxia's, memory disorders, and a growing list of neurological
disorders.
PMID- 26422984
TI - Structural Insights into GIRK Channel Function.
AB - G protein-gated inwardly rectifying potassium (GIRK; Kir3) channels, which are
members of the large family of inwardly rectifying potassium channels (Kir1
Kir7), regulate excitability in the heart and brain. GIRK channels are activated
following stimulation of G protein-coupled receptors that couple to the G(i/o)
(pertussis toxin-sensitive) G proteins. GIRK channels, like all other Kir
channels, possess an extrinsic mechanism of inward rectification involving
intracellular Mg(2+) and polyamines that occlude the conduction pathway at
membrane potentials positive to E(K). In the past 17 years, more than 20 high
resolution atomic structures containing GIRK channel cytoplasmic domains and
transmembrane domains have been solved. These structures have provided valuable
insights into the structural determinants of many of the properties common to all
inward rectifiers, such as permeation and rectification, as well as revealing the
structural bases for GIRK channel gating. In this chapter, we describe advances
in our understanding of GIRK channel function based on recent high-resolution
atomic structures of inwardly rectifying K(+) channels discussed in the context
of classical structure-function experiments.
PMID- 26422985
TI - Localization and Targeting of GIRK Channels in Mammalian Central Neurons.
AB - G protein-gated inwardly rectifying K(+) (GIRK/K(ir)3) channels are critical to
brain function. They hyperpolarize neurons in response to activation of different
G protein-coupled receptors, reducing cell excitability. Molecular cloning has
revealed four distinct mammalian genes (GIRK1-4), which, with the exception of
GIRK4, are broadly expressed in the central nervous system (CNS) and have been
implicated in a variety of neurological disorders. Although the molecular
structure and composition of GIRK channels are key determinants of their
biophysical properties, their cellular and subcellular localization patterns and
densities on the neuronal surface are just as important to nerve function.
Current data obtained with high-resolution quantitative localization techniques
reveal complex, subcellular compartment-specific distribution patterns of GIRK
channel subunits. Recent efforts have focused on determining the associated
proteins that form macromolecular complexes with GIRK channels. Demonstration of
the precise subcellular compartmentalization of GIRK channels and their
associated proteins represents a crucial step in understanding the contribution
of these channels to specific aspects of neuronal function under both
physiological and pathological conditions. Here, we present an overview of
studies aimed at determining the cellular and subcellular localization of GIRK
channel subunits in mammalian brain neurons and discuss implications for neuronal
physiology.
PMID- 26422986
TI - GIRK Channel Plasticity and Implications for Drug Addiction.
AB - Drugs of abuse can "hijack" synaptic plasticity, a physiological basis of
learning and memory, establishing maladaptations that can promote drug addiction.
A wealth of data supports the existence and importance of neuroadaptations in
excitatory neurotransmission upon drug exposure. Recent discoveries, however,
have shown that inhibitory neurotransmission mediated by G protein-gated inwardly
rectifying potassium (K(+)) (GIRK/Kir3) channels is also subject to adaptation
triggered by exposure to drugs of abuse. GIRK channels are expressed in neuronal
populations relevant to reward and reward-related behaviors, where their
activation by neurotransmitters such as GABA, dopamine, and adenosine reduces
neuronal excitability. Studies in animal models have implicated GIRK channels in
a number of behaviors including reward. Drugs of abuse also affect the inhibitory
neurotransmission mediated by GIRK channels. These changes might be important for
the development, maintenance, or relapse of addiction, making GIRK channels
promising targets for novel addiction therapies.
PMID- 26422987
TI - GIRK Channels: A Potential Link Between Learning and Addiction.
AB - The ability of drug-associated cues to reinitiate drug craving and seeking, even
after long periods of abstinence, has led to the hypothesis that addiction
represents a form of pathological learning, in which drugs of abuse hijack normal
learning and memory processes to support long-term addictive behaviors. In this
chapter, we review evidence suggesting that G protein-gated inwardly rectifying
potassium (GIRK/Kir3) channels are one mechanism through which numerous drugs of
abuse can modulate learning and memory processes. We will examine the role of
GIRK channels in two forms of experience-dependent long-term changes in neuronal
function: homeostatic plasticity and synaptic plasticity. We will also discuss
how drug-induced changes in GIRK-mediated signaling can lead to changes that
support the development and maintenance of addiction.
PMID- 26422989
TI - Preface.
PMID- 26422991
TI - Vitis vinifera L. Single-Nucleotide Polymorphism Detection with High-Resolution
Melting Analysis Based on the UDP-Glucose:Flavonoid 3-O-Glucosyltransferase Gene.
AB - Vitis vinifera L. is a species with a large number of varieties, which differ in
terms of anthocyanin content. The genes involved in the anthocyanin biosynthesis
pathway have a direct effect in the anthocyanin profile of each variety, being
potentially interesting for varietal identification. The current study aimed at
the design of an assay suitable for the discrimination of the largest number of
grapevine varieties. Two genes of the anthocyanin pathway, chalcone isomerase
(CHI) and UDP-glucose:flavonoid 3-O-glucosyltransferase (UFGT), were sequenced in
22 grapevine varieties. The CHI gene presented 5 SNPs within the sequence. A
total of 58 SNPs and 1 INDEL were found among the UFGT gene, allowing the
discrimination of 18 different genotypes within the 22 grapevine varieties. A HRM
assay designed for UFGT, containing 704 bp, produced differentiated melting
curves for each of the 18 haplotypes. The developed HRM assay is efficient in
grapevine varietal discrimination.
PMID- 26422990
TI - Palmitate-induced endothelial dysfunction is attenuated by cyanidin-3-O-glucoside
through modulation of Nrf2/Bach1 and NF-kappaB pathways.
AB - Free fatty acids (FFA), commonly elevated in diabetes and obesity, have been
shown to impair endothelial functions and cause oxidative stress, inflammation,
and insulin resistance. Anthocyanins represent one of the most important and
interesting classes of flavonoids and seem to play a role in preventing
cardiovascular diseases. Herein, we investigated the in vitro protective effects
of cyanidin-3-O-glucoside (C3G) on cell signaling pathways in human umbilical
vein endothelial cells (HUVECs) exposed to palmitic acid (PA), the most prevalent
saturated FFA in circulation. Our data reported a significant augmentation of
free radicals and oxidative stress in HUVECs exposed to PA for 3h, while C3G
pretreatment improved intracellular redox status altered by FFA. Moreover, C3G
significantly inhibited NF-kappaB proinflammatory pathway and adhesion molecules
induced by PA, and these effects were attributed to the activation of Nrf2/EpRE
pathway. In fact, C3G induced Nrf2 nuclear localization and activation of
cellular antioxidant and cytoprotective genes at baseline and after PA exposure
in endothelial cells. Our data confirm the hypothesis that natural Nrf2 inducers,
such as C3G, might be a potential therapeutic strategy to protect vascular system
against various stressors preventing several pathological conditions.
PMID- 26422988
TI - Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology,
Pathophysiology, and Drug Addiction.
AB - G protein-coupled inwardly rectifying potassium (GIRK) channels are widely
expressed throughout the brain and mediate the inhibitory effects of many
neurotransmitters. As a result, these channels are important for normal CNS
function and have also been implicated in Down syndrome, Parkinson's disease,
psychiatric disorders, epilepsy, and drug addiction. Knockout mouse models have
provided extensive insight into the significance of GIRK channels under these
conditions. This review examines the behavioral and genetic evidence from animal
models and genetic association studies in humans linking GIRK channels with CNS
disorders. We further explore the possibility that subunit-selective modulators
and other advanced research tools will be instrumental in establishing the role
of individual GIRK subunits in drug addiction and other relevant CNS diseases and
in potentially advancing treatment options for these disorders.
PMID- 26422992
TI - Differential phenotypic and functional properties of liver-resident NK cells and
mucosal ILC1s.
AB - Group 1 innate lymphoid cells (ILCs) consist of conventional natural killer (cNK)
cells, tissue-resident NK cells and mucosal ILC1s. Recently identified liver
resident NK cells, which can mount contact hypersensitivity responses, and
mucosal ILC1s that are involved in pathogenesis of colitis are distinct from cNK
cells in several aspects, but the issue of how they are related to each other has
not been clearly clarified. Here, we show that liver-resident NK cells and
mucosal ILC1s have different phenotypes, as evidenced by distinct expression
patterns of homing-associated molecules. Moreover, mucosal ILC1s exhibit tissue
residency akin to liver-resident NK cells. Importantly, liver-resident NK cells
express relative high levels of cytotoxic effector molecules, which are poorly
expressed by mucosal ILC1s, and exhibit stronger cytotoxic activity compared with
mucosal ILC1s. These results demonstrate differential phenotypic and functional
characteristics of liver-resident NK cells and mucosal ILC1s, shedding new light
on the diversity of ILC family.
PMID- 26422993
TI - Mucosal signaling in the bladder.
AB - The bladder mucosa is comprised of the multilayered urothelium, lamina propria
(LP), microvasculature, and smooth muscle fibers (muscularis mucosae). The
muscularis mucosae is not always present in the mucosa, and its presence is
related to the thickness of the LP. Since there are no mucus secreting cells,
"mucosa" is an imprecise term. Nerve fibers are present in the LP of the mucosa.
Efferent nerves mediate mucosal contractions which can be elicited by electrical
field stimulation (EFS) and various agonists. The source of mucosal contractility
is unknown, but may arise from the muscularis mucosae or myofibroblasts. EFS also
increases frequency of mucosal venule contractions. Thus, efferent neural
activity has multiple effects on the mucosa. Afferent activity has been measured
when the mucosa is stimulated by mechanical and stretch stimuli from the luminal
side. Nerve fibers have been shown to penetrate into the urothelium, allowing
urothelial cells to interact with nerves. Myofibroblasts are specialized cells
within the LP that generate spontaneous electrical activity which then can
modulate both afferent and efferent neural activities. Thus mucosal signaling is
defined as interactions between bladder autonomic nerves with non-neuronal cells
within the mucosa. Mucosal signaling is likely to be involved in clinical
functional hypersensory bladder disorders (e.g. overactive bladder, urgency,
urgency incontinence, bladder pain syndrome) in which mechanisms are poorly
understood despite high prevalence of these conditions. Targeting aberrant
mucosal signaling could represent a new approach in treating these disorders.
PMID- 26422994
TI - Indiana HIV outbreak should inspire long-term changes.
PMID- 26422996
TI - How to motivate hard-to-reach men to accept circumcision.
PMID- 26422997
TI - Psychological therapy to improve HIV care and reduce stigma.
PMID- 26422998
TI - The link between modelling and doing.
PMID- 26422999
TI - ART coverage in Rwanda: successes and remaining challenges.
PMID- 26423000
TI - Definitions of implementation science in HIV/AIDS.
PMID- 26423001
TI - Group support psychotherapy for depression treatment in people with HIV/AIDS in
northern Uganda: a single-centre randomised controlled trial.
AB - BACKGROUND: Group support psychotherapy (GSP) is a culturally sensitive
intervention that aims to treat depression by enhancing social support, teaching
coping skills, and income-generating skills. We compared GSP with group HIV
education (GHE) for treatment of depression in people with HIV in Uganda.
METHODS: In this open-label randomised controlled trial, we included men and
women with HIV, aged 19 years or older, who met the Mini International
Neuropsychiatric Interview criteria for major depression from an urban HIV care
centre in Kitgum district, northern Uganda. Participants were randomly assigned
to receive eight weekly sessions of either GSP or GHE. Randomisation was achieved
by urn (men and women separately picked a paper containing the intervention
allocation from a basket; ratio 1:1), and the intervention sessions were given to
gender-specific groups. Participants were followed up immediately after the
intervention and 6 months after the end of treatment. The primary outcomes were
change in depressive symptom scores (measured with the Self-Reporting
Questionnaire) and in function scores (measured with a locally developed method),
analysed by intention to treat using cluster-adjusted t tests and permutation
tests. This trial is registered with The Pan African Clinical Trials Registry,
number PACTR201402000742370. FINDINGS: Between Jan 6, and Jan 20, 2014, we
assessed 150 individuals, of whom 109 were randomly assigned to receive eight
weekly sessions of either GSP (n=57) or GHE (n=52). Change in mean depression
scores immediately after intervention did not differ between groups (mean
difference -0.19, 95% CI -1.77 to 1.39, p=0.78). Mean function scores did not
differ between groups either (0.24, -0.41 to 0.88; p=0.41). At 6 months after end
of treatment, participants in the GSP group had lower mean depression scores than
did those in the GHE group (-2.50, -3.98 to 1.02, p value=0.005), and higher
function scores (0.74, -0.17 to 1.65, p=0.09) than did participants in the GHE
group. No adverse events were reported. INTERPRETATION: The benefits of existing
HIV educational interventions in HIV care services could be improved by the
addition of GSP content. Potential benefits of the integration of GSP into
existing HIV interventions, such as adherence counselling or group HIV
educational programmes, should be addressed in future studies. FUNDING: Grand
Challenges Canada.
PMID- 26423002
TI - Scaling up of HIV treatment for men who have sex with men in Bangkok: a modelling
and costing study.
AB - BACKGROUND: Despite the high prevalence of HIV in men who have sex with men (MSM)
in Bangkok, little investment in HIV prevention for MSM has been made. HIV
testing and treatment coverage remains low. Through a pragmatic programme
planning approach, we assess possible service linkage and provision of HIV
testing and antiretroviral treatment (ART) to MSM in Bangkok, and the most cost
effective scale-up strategy. METHODS: We obtained epidemiological and service
capacity data from the Thai National Health Security Office database for 2011. We
surveyed 13 representative medical facilities for detailed operational costs of
HIV-related services for sexually active MSM (defined as having sex with men in
the past 12 months) in metropolitan Bangkok. We estimated the costs of various
ART scale-up scenarios, accounting for geographical accessibility across Bangkok.
We used an HIV transmission population-based model to assess the cost
effectiveness of the scenarios. FINDINGS: For present HIV testing (23% [95% CI 17
36] of MSM at high risk in 2011) and ART provision (20% of treatment-eligible MSM
at high risk on ART in 2011) to be sustained, a US$73.8 million ($51.0 million to
$97.0 million) investment during the next decade would be needed, which would
link an extra 43,000 (27,900-58,000) MSM at high risk to HIV testing and 5100
(3500-6700) to ART, achieving an ART coverage of 44% for MSM at high risk in
2022. An additional $55.3 million investment would link an extra 46,700 (30,300
63,200) MSM to HIV testing and 12,600 (8800-16,600) to ART, achieving universal
ART coverage of this population by 2022. This increased investment is achievable
within present infrastructure capacity. Consequently, an estimated 5100 (3600
6700) HIV-related deaths and 3700 (2600-4900) new infections could be averted in
MSM by 2022, corresponding to a 53% reduction in deaths and a 35% reduction in
infections from 2012 levels. The expansion would cost an estimated $10,809 (9071
13,274) for each HIV-related death, $14,783 (12,389-17,960) per new infection
averted, and $351 (290-424) per disability-adjusted life-year averted.
INTERPRETATION: Spare capacity in Bangkok's medical facilities can be used to
expand ART access for MSM with large epidemiological benefits. The expansion
needs increased funding directed to MSM services, but given the epidemiological
trends, is probably cost effective. Our modelling approach and outcomes are
likely to be applicable to other settings. FUNDING: World Bank Group and
Australian National Health and Medical Research Council.
PMID- 26423003
TI - HIV care continuum in Rwanda: a cross-sectional analysis of the national
programme.
AB - BACKGROUND: Rwanda has made remarkable progress towards HIV care programme with
strong national monitoring and surveillance. Knowledge about the HIV care
continuum model can help to improve outcomes in patients. We aimed to quantify
engagement, mortality, and loss to follow-up of patients along the HIV care
continuum in Rwanda in 2013. METHODS: We collated data for individuals with HIV
who participated in the national HIV care programme in Rwanda and calculated the
numbers of individuals or proportions of the population at each stage and the
transition probabilities between stages of the continuum. We calculated factors
associated with mortality and loss to follow-up by fitting Cox proportional
hazards regression models, one for the stage of care before antiretroviral
therapy (ART) initiation and another for stage of care during ART. FINDINGS: An
estimated 204,899 individuals were HIV-positive in Rwanda in 2013. Among these
individuals, 176,174 (86%) were in pre-ART or in ART stages and 129,405 (63%) had
initiated ART by the end of 2013. 82.1% (95% CI 80.7-83.4) of patients with viral
load measurements (n=3066) were virally suppressed (translating to 106,371
individuals or 52% of HIV-positive individuals). Mortality was 0.6% (304
patients) in the pre-ART stage and 1.0% (1255 patients) in the ART stage; 2247
(3.9%) patients were lost to follow-up in pre-ART stage and 2847 (2.2%) lost in
ART stage. Risk factors for mortality among patients in both pre-ART and ART
stages included older age, CD4 cell count at initiation, and male sex. Risk
factors for loss to follow-up among patients at both pre-ART and ART stages
included younger age (age 10-29 year) and male sex. INTERPRETATION: The HIV care
continuum is a multitrajectory pathway in which patients have many opportunities
to leave and re-engage in care. Knowledge about the points at which individuals
are most likely to leave care could improve large-scale delivery of HIV
programmes. FUNDING: The Bill & Melinda Gates Foundation.
PMID- 26423005
TI - Protein Transfer Free Energy Obeys Entropy-Enthalpy Compensation.
AB - We have found significant entropy-enthalpy compensation for the transfer of a
diverse set of two-state folding proteins from water into water containing a
diverse set of cosolutes, including osmolytes, denaturants, and crowders. In
extracting thermodynamic parameters from experimental data, we show the potential
importance of accounting for the cosolute concentration-dependence of the heat
capacity change upon unfolding, as well as the potential importance of the
temperature-dependence of the heat capacity change upon unfolding. We introduce a
new Monte Carlo method to estimate the experimental uncertainty in the
thermodynamic data and use this to show by bootstrapping methods that entropy
enthalpy compensation is statistically significant, in spite of large, correlated
scatter in the data. We show that plotting the data at the transition midpoint
provides the most accurate experimental values by avoiding extrapolation errors
due to uncertainty in the heat capacity, and that this representation exhibits
the strongest evidence of compensation. Entropy-enthalpy compensation is still
significant at lab temperature however. We also find that compensation is still
significant when considering variations due to heat capacity models, as well as
typical measurement discrepancies lab-to-lab when such data is available.
Extracting transfer entropy and enthalpy along with their uncertainties can
provide a valuable consistency check between experimental data and simulation
models, which may involve tests of simulated unfolded ensembles and/or models of
the transfer free energy; we include specific applications to cold shock protein
and protein L.
PMID- 26423006
TI - Comparison of proteome typing and serotyping of Streptococcus parauberis isolates
from olive flounder (Paralichthys olivaceus).
AB - The olive flounder (Paralichthys olivaceus) is a cultivated marine species that
is economically important in Korea and Japan. Several bacterial pathogens have
caused severe mortalities in farmed olive flounder, especially Streptococcus
parauberis. We collected 145 S. parauberis isolates from diseased olive flounders
from 2003 to 2008 in Jeju Island, South Korea and characterized them by Matrix
assisted laser desorption ionization-time of flight mass spectrometry (MALDI TOF
MS) and by serology. The serological analysis divided the isolates into serotype
I (62.1%) and serotype II (36.6%) and the proteome analysis divided the isolates
into cluster 1 (43.4%) and cluster 2 (56.6%). All cluster 1 isolates had serotype
I, but cluster 2 consisted of serotype I (32.9%), serotype II (64.6%), and others
(2.5%). Further detailed analysis of the mass spectra led to identification of
several specific m/z peaks that enabled discrimination between cluster 1 and 2
and between serotype I and II within cluster 2. Our results suggest that MALDI
TOF MS analysis has potential as an alternative method for the rapid and reliable
identification of the fish pathogen S. parauberis.
PMID- 26423004
TI - The structural basis of Miranda-mediated Staufen localization during Drosophila
neuroblast asymmetric division.
AB - During the asymmetric division of Drosophila neuroblasts (NBs), the scaffold
Miranda (Mira) coordinates the subcellular distribution of cell-fate determinants
including Staufen (Stau) and segregates them into the ganglion mother cells
(GMCs). Here we show the fifth double-stranded RNA (dsRNA)-binding domain
(dsRBD5) of Stau is necessary and sufficient for binding to a coiled-coil region
of Mira cargo-binding domain (CBD). The crystal structure of Mira514-595/Stau
dsRBD5 complex illustrates that Mira forms an elongated parallel coiled-coil
dimer, and two dsRBD5 symmetrically bind to the Mira dimer through their exposed
beta-sheet faces, revealing a previously unrecognized protein interaction mode
for dsRBDs. We further demonstrate that the Mira-Stau dsRBD5 interaction is
responsible for the asymmetric localization of Stau during Drosophila NB
asymmetric divisions. Finally, we find the CBD-mediated dimer assembly is likely
a common requirement for Mira to recognize and translocate other cargos including
brain tumour (Brat).
PMID- 26423009
TI - Animal Obesity - causes, consequences and comparative aspects: meeting abstracts.
PMID- 26423007
TI - Design and characterization of calcium phosphate ceramic scaffolds for bone
tissue engineering.
AB - OBJECTIVES: Our goal is to review design strategies for the fabrication of
calcium phosphate ceramic scaffolds (CPS), in light of their transient role in
bone tissue engineering and associated requirements for effective bone
regeneration. METHODS: We examine the various design options available to meet
mechanical and biological requirements of CPS and later focus on the importance
of proper characterization of CPS in terms of architecture, mechanical properties
and time-sensitive properties such as biodegradability. Finally, relationships
between in vitro versus in vivo testing are addressed, with an attempt to
highlight reliable performance predictors. RESULTS: A combinatory design strategy
should be used with CPS, taking into consideration 3D architecture, adequate
surface chemistry and topography, all of which are needed to promote bone
formation. CPS represent the media of choice for delivery of osteogenic factors
and anti-infectives. Non-osteoblast mediated mineral deposition can confound in
vitro osteogenesis testing of CPS and therefore the expression of a variety of
proteins or genes including collagen type I, bone sialoprotein and osteocalcin
should be confirmed in addition to increased mineral content. CONCLUSIONS: CPS
are a superior scaffold material for bone regeneration because they actively
promote osteogenesis. Biodegradability of CPS via calcium and phosphate release
represents a unique asset. Structural control of CPS at the macro, micro and
nanoscale and their combination with cells and polymeric materials is likely to
lead to significant developments in bone tissue engineering.
PMID- 26423008
TI - Secondary caries and microleakage.
AB - OBJECTIVES: To critically appraise experimental ex vivo research that has focused
on secondary caries, and to offer possible explanations for the seemingly poor
correlation to clinical observations. METHODS: The literature relating to the
etiopathogenesis or prevention of secondary caries gained from experimental ex
vivo research was reviewed, with particular emphasis on microleakage and
artificial caries-like lesions. RESULTS: It is doubtful whether a caries wall
lesion can exist independently of an outer enamel caries lesion. Microleakage
experiments apparently continue to emerge regardless of multiple reviews
questioning the reliability and validity of the method. Several of the approaches
used to generate artificial caries-like lesions are very aggressive. Remarkably
little discussion has evolved about how these aggressive approaches create
microenvironments that do not occur in reality. Corrosion- and biodegradation
products may influence the biofilm qualitatively and quantitatively and it is
difficult to replicate these variables in any ex vivo environment. Clinical data
sampling method, patient demography as well as study methodology influences the
incidence and prevalence estimates of secondary caries. Clinical results based on
clinical work in settings where cost per unit time is of nominal concern do not
provide any indications on how the restorative material will perform when placed
by the average dentists in the mouths of their spectrum of patients during a busy
workday. SIGNIFICANCE AND RECOMMENDATIONS: The term "wall lesion" including its
variants is ill defined, has been, and is still being used indiscriminately.
Stakeholders should avoid using this ambiguous label due to its connotation to an
entity that does not exist per se.
PMID- 26423010
TI - Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte
Multilayer Films for Local Therapeutic Delivery.
AB - The ability to control the spatial distribution and temporal release of a
therapeutic remains a central challenge for biomedical research. Here, we report
the development and optimization of a novel substrate mediated therapeutic
delivery system comprising of hyaluronic acid covalently functionalized liposomes
(HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic
stabilization. The PEM platform was constructed from sequential deposition of
Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) "(PLL/SPS)4.5"
followed by adsorption of anionic HALNPs. An adsorption affinity assay and
saturation curve illustrated the preferential HALNP deposition density for
precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited
HALNP monolayer further facilitated complete nanoparticle immobilization, cell
adhesion, and provided nanoparticle confinement for controlled linear release
profiles of the nanocarrier and encapsulated cargo. To our knowledge, this is the
first study to demonstrate the successful embedment of a translatable lipid based
nanocarrier into a substrate that allows for temporal and spatial release of both
hydrophobic and hydrophilic drugs. Specifically, we have utilized our platform to
deliver chemotherapeutic drug Doxorubicin from PEM confined HALNPs. Overall, we
believe the development of our HALNP embedded PEM system is significant and will
catalyze the usage of substrate mediated delivery platforms in biomedical
applications.
PMID- 26423012
TI - Elucidating COPD pathogenesis by large-scale genetic analyses.
PMID- 26423013
TI - Monitoring the health of the work environment with a daily assessment tool: the
REAL - Relative Environment Assessment Lens - indicator.
AB - BACKGROUND: Evidence shows that the health of the work environment impacts staff
satisfaction, interdisciplinary communication, and patient outcomes. Utilising
the American Association of Critical-Care Nurses' Healthy Work Environment
standards, we developed a daily assessment tool. METHODS: The Relative
Environment Assessment Lens (REAL) Indicator was developed using a consensus
based method to evaluate the health of the work environment and to identify
opportunities for improvement from the front-line staff. A visual scale using
images that resemble emoticons was linked with a written description of feelings
about their work environment that day, with the highest number corresponding to
the most positive experience. Face validity was established by seeking staff
feedback and goals were set. RESULTS: Over 10 months, results from the REAL
Indicator in the cardiac catheterisation laboratory indicated an overall good
work environment. The goal of 80% of the respondents reporting their work
environment to be "Great", "Good", or "Satisfactory" was met each month. During
the same time frame, this goal was met four times in the cardiovascular operating
room. On average, 72.7% of cardiovascular operating room respondents reported
their work environment to be "Satisfactory" or better. CONCLUSION: The REAL
Indicator has become a valuable tool in assessing the specific issues of the
clinical area and identifying opportunities for improvement. Given the
feasibility of and positive response to this tool in the cardiac catheterisation
laboratory, it has been adopted in other patient-care areas where staff and
leaders believe that they need to understand the health of the environment in a
more specific and frequent time frame.
PMID- 26423016
TI - Corrigendum: Lattice Distortion in In3SbTe2 Phase Change Material with
Substitutional Bi.
PMID- 26423015
TI - Optimizing plasmonic nanoantennas via coordinated multiple coupling.
AB - Plasmonic nanoantennas, which can efficiently convert light from free space into
sub-wavelength scale with the local field enhancement, are fundamental building
blocks for nanophotonic systems. Predominant design methods, which exploit a
single type of near- or far-field coupling in pairs or arrays of plasmonic
nanostructures, have limited the tunability of spectral response and the local
field enhancement. To overcome this limit, we are developing a general strategy
towards exploiting the coordinated effects of multiple coupling. Using Au bowtie
nanoantenna arrays with metal-insulator-metal configuration as examples, we
numerically demonstrate that coordinated design and implementation of various
optical coupling effects leads to both the increased tunability in the spectral
response and the significantly enhanced electromagnetic field. Furthermore, we
design and analyze a refractive index sensor with an ultra-high figure-of-merit
(254), a high signal-to-noise ratio and a wide working range of refractive
indices, and a narrow-band near-infrared plasmonic absorber with 100% absorption
efficiency, high quality factor of up to 114 and a wide range of tunable
wavelength from 800 nm to 1,500 nm. The plasmonic nanoantennas that exploit
coordinated multiple coupling will benefit a broad range of applications,
including label-free bio-chemical detection, reflective filter, optical trapping,
hot-electron generation, and heat-assisted magnetic recording.
PMID- 26423014
TI - High-dose esomeprazole and amoxicillin dual therapy for first-line Helicobacter
pylori eradication: a proof of concept study.
AB - BACKGROUND: The prevalence of resistance to clarithromycin and metronidazole has
considerably increased, with a corresponding decrease in the eradication rate for
Helicobacter pylori (H. pylori) infection. Primary resistance to amoxicillin is
extremely low, and esomeprazole was found to exert a noteworthy antimicrobial
activity in vitro against H. pylori. A dual therapy with high-dose of
esomeprazole coupled with high-dose amoxicillin might be therefore an ideal first
line treatment for H. pylori eradication. We aimed to assess the efficacy of a
first-line 10-day, high-dose dual therapy consisting of amoxicillin and
esomeprazole to eradicate H. pylori infection. METHODS: Consecutive naive H.
pylori-infected patients, who underwent an upper endoscopy in 4 Italian hospitals
due to dyspeptic symptoms and found to be infected at routine histological
assessment, were invited to participate. Patients enrolled received a 10-day,
high-dose dual therapy comprising esomeprazole (40 mg t.i.d) and amoxicillin (1 g
t.i.d.). At least 4 weeks after the end of the treatment a (13)C-urea breath test
was performed to evaluate the eradication. RESULTS: A total of 56 patients agreed
to participate in the study and were all followed-up. The overall eradication was
87.5% (95% CI=78.8*96.2), without a statistically significant difference among
centres. Overall, 5 (8.9%; 1.5*16.4%) patients complained of side-effects.
CONCLUSIONS: The 10-day, high-dose dual therapy with esomeprazole and amoxicillin
might be an effective and safe first-line regimen. The efficacy of a longer 14
day regimen should be tested.
PMID- 26423017
TI - Fractional flow reserve-guided paclitaxel-coated balloon treatment for de novo
coronary lesions.
AB - OBJECTIVES: To assess the safety and efficacy of fractional flow reserve (FFR)
guided paclitaxel-coated balloon (PCB) treatment for de novo coronary artery
lesions. BACKGROUND: There is limited data on PCB treatment for de novo lesions
especially of major epicardial coronary arteries. METHODS: Sixty-six patients
with 67 de novo lesions who underwent successful plain old balloon angioplasty
(POBA) were included. If POBA-FFR was favorable (>= 0.85), PCB was applied and if
POBA-FFR was <0.85, stent implantation was preferred over PCB. RESULTS: Forty
five lesions were treated with PCB (67.2%) and 22 lesions with stents (32.8%).
Dual antiplatelet therapy duration was 6 weeks. Late luminal loss with PCB was
significantly less than stent (0.05 +/- 0.27 mm vs. 0.40 +/- 0.54 mm, P = 0.022).
The baseline FFR of target lesions was 0.69 +/- 0.16 in PCB and 0.60 +/- 0.11 in
stent group (P = 0.015), however, the FFR at 9 months was not different between
groups (0.85 +/- 0.08 in PCB vs. 0.85 +/- 0.05 in stent group, P = 0.973). At 1
year, one myocardial infarction and one target lesion revascularization related
to in-stent restenosis were detected, both in the stent group. CONCLUSION: POBA
FFR-guided PCB treatment is safe and effective for de novo coronary lesions with
good anatomical and physiological patency at mid-term follow-up. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26423011
TI - Novel insights into the genetics of smoking behaviour, lung function, and chronic
obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK
Biobank.
AB - BACKGROUND: Understanding the genetic basis of airflow obstruction and smoking
behaviour is key to determining the pathophysiology of chronic obstructive
pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of
smoking behaviour and lung health. METHODS: We sampled individuals of European
ancestry from UK Biobank, from the middle and extremes of the forced expiratory
volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and
never smokers. We developed a custom array for UK Biobank to provide optimum
genome-wide coverage of common and low-frequency variants, dense coverage of
genomic regions already implicated in lung health and disease, and to assay rare
coding variants relevant to the UK population. We investigated whether there were
shared genetic causes between different phenotypes defined by extremes of FEV1.
We also looked for novel variants associated with extremes of FEV1 and smoking
behaviour and assessed regions of the genome that had already shown evidence for
a role in lung health and disease. We set genome-wide significance at p<5 * 10(
8). FINDINGS: UK Biobank participants were recruited from March 15, 2006, to July
7, 2010. Sample selection for the UK BiLEVE study started on Nov 22, 2012, and
was completed on Dec 20, 2012. We selected 50,008 unique samples: 10,002
individuals with low FEV1, 10,000 with average FEV1, and 5002 with high FEV1 from
each of the heavy smoker and never smoker groups. We noted a substantial sharing
of genetic causes of low FEV1 between heavy smokers and never smokers (p=2.29 *
10(-16)) and between individuals with and without doctor-diagnosed asthma (p=6.06
* 10(-11)). We discovered six novel genome-wide significant signals of
association with extremes of FEV1, including signals at four novel loci (KANSL1,
TSEN54, TET2, and RBM19/TBX5) and independent signals at two previously reported
loci (NPNT and HLA-DQB1/HLA-DQA2). These variants also showed association with
COPD, including in individuals with no history of smoking. The number of copies
of a 150 kb region containing the 5' end of KANSL1, a gene that is important for
epigenetic gene regulation, was associated with extremes of FEV1. We also
discovered five new genome-wide significant signals for smoking behaviour,
including a variant in NCAM1 (chromosome 11) and a variant on chromosome 2
(between TEX41 and PABPC1P2) that has a trans effect on expression of NCAM1 in
brain tissue. INTERPRETATION: By sampling from the extremes of the lung function
distribution in UK Biobank, we identified novel genetic causes of lung function
and smoking behaviour. These results provide new insight into the specific
mechanisms underlying airflow obstruction, COPD, and tobacco addiction, and show
substantial shared genetic architecture underlying airflow obstruction across
individuals, irrespective of smoking behaviour and other airway disease. FUNDING:
Medical Research Council.
PMID- 26423018
TI - Chronic Phase Intracranial Hemorrhage Caused by Ruptured Pseudoaneurysm Induced
by Carmustine Wafer Implantation for Insulo-opercular Anaplastic Astrocytoma: A
Case Report.
AB - Carmustine wafers improve the survival of patients with high-grade gliomas, but
several adverse events have been reported. A 42-year-old man with left Insulo
opercular anaplastic astrocytoma developed a massive intra-cavital hematoma with
subarachnoid hemorrhage caused by ruptured pseudoaneurysm of the left middle
cerebral artery (MCA) adjacent to the site of carmustine wafers implanted 6
months previously. Intraoperative finding demonstrated a dissection of the
insular portion of the MCA, and pathological examination identified the resected
pseudoaneurysm. This case demonstrates that carmustine wafers can cause changes
in local vessels. Therefore, implantation of carmustine wafers near to important
vessels passing close to the resection cavity should be considered with great
caution.
PMID- 26423019
TI - Platelet density per monocyte predicts adverse events in patients after
percutaneous coronary intervention.
AB - Monocyte recruitment to damaged endothelium is enhanced by platelet binding to
monocytes and contributes to vascular repair. Therefore, we studied whether the
number of platelets per monocyte affects the recurrence of adverse events in
patients after percutaneous coronary intervention (PCI). Platelet-monocytes
complexes with high and low median fluorescence intensities (MFI) of the platelet
marker CD42b were isolated using cell sorting. Microscopic analysis revealed that
a high platelet marker MFI on monocytes corresponded with a high platelet density
per monocyte while a low platelet marker MFI corresponded with a low platelet
density per monocyte (3.4 +/- 0.7 vs 1.4 +/- 0.1 platelets per monocyte, P=0.01).
Using real-time video microscopy, we observed increased recruitment of high
platelet density monocytes to endothelial cells as compared with low platelet
density monocytes (P=0.01). Next, we classified PCI scheduled patients (N=263)
into groups with high, medium and low platelet densities per monocyte and
assessed the recurrence of adverse events. After multivariate adjustment for
potential confounders, we observed a 2.5-fold reduction in the recurrence of
adverse events in patients with a high platelet density per monocyte as compared
with a low platelet density per monocyte [hazard ratio=0.4 (95% confidence
interval, 0.2-0.8), P=0.01]. We show that a high platelet density per monocyte
increases monocyte recruitment to endothelial cells and predicts a reduction in
the recurrence of adverse events in patients after PCI. These findings may imply
that a high platelet density per monocyte protects against recurrence of adverse
events.
PMID- 26423020
TI - Approach for classification and taxonomy within family Rickettsiaceae based on
the Formal Order Analysis.
AB - Genome sequences of 36 Rickettsia and Orientia were analyzed using Formal Order
Analysis (FOA). This approach takes into account arrangement of nucleotides in
each sequence. A numerical characteristic, the average distance (remoteness) -
"g" was used to compare of genomes. Our results corroborated previous separation
of three groups within the genus Rickettsia, including typhus group, classic
spotted fever group, and the ancestral group and Orientia as a separate genus.
Rickettsia felis URRWXCal2 and R. akari Hartford were not in the same group based
on FOA, therefore designation of a so-called transitional Rickettsia group could
not be confirmed with this approach.
PMID- 26423021
TI - Permissivity of insect cells to Waddlia chondrophila, Estrella lausannensis and
Parachlamydia acanthamoebae.
AB - Recent large scale studies questioning the presence of intracellular bacteria of
the Chlamydiales order in ticks and fleas revealed that arthropods, similarly to
mammals, reptiles, birds or fishes, can be colonized by Chlamydia-related
bacteria with a predominant representation of the Rhabdochlamydiaceae and
Parachlamydiaceae families. We thus investigated the permissivity of two insect
cell lines towards Waddlia chondrophila, Estrella lausannensis and Parachlamydia
acanthamoebae, three bacteria representative of three distinct families within
the Chlamydiales order, all documented in ticks and/or in other arthropods. We
demonstrated that W. chondrophila and E. lausannensis are able to very
efficiently multiply in these insect cell lines. E. lausannensis however induced
a rapid cytopathic effect, which somehow restricted its replication. P.
acanthamoebae was not able to grow in these cell lines even if inclusions
containing a few replicating bacteria could occasionally be observed.
PMID- 26423022
TI - Rates of inbreeding and genetic adaptation for populations managed as herds in
zoos with a rotational mating system or with optimized contribution of parents.
AB - This study compares two genetic management scenarios for species kept in herds,
such as deer. The simulations were designed so that their results can be extended
to a wide range of zoo populations. In the first scenario, the simulated
populations of size 3 * 20, 6 * 40 or 20 * 60 (herds * animals in herd) were
managed with a rotational mating (RM) scheme in which 10%, 20% or 50% of males
were selected for breeding and moved between herds in a circular fashion. The
second scenario was based on optimal contribution theory (OC). OC requires an
accurate pedigree to calculate kinship; males were selected and assigned numbers
of offspring to minimize kinship in the next generation. RM was efficient in
restriction of inbreeding and produced results comparable with OC. However, RM
can result in genetic adaptation of the population to the zoo environment, in
particular when 20% or less males are selected for rotation and selection of
animals is not random. Lowest rates of inbreeding were obtained by combining OC
with rotation of males as in the RM scheme. RM is easy to implement in practice
and does not require pedigree data. When full pedigree is available, OC
management is preferable.
PMID- 26423023
TI - The effect of sagittal rotation of the glenoid on axial glenoid width and glenoid
version in computed tomography scan imaging.
AB - BACKGROUND: Computed tomography (CT) scans of the shoulder are often not well
aligned to the axis of the scapula and glenoid. The purpose of this paper was to
determine the effect of sagittal rotation of the glenoid on axial measurements of
anterior-posterior (AP) glenoid width and glenoid version attained by standard CT
scan. In addition, we sought to define the angle of rotation required to correct
the CT scan to optimal positioning. METHODS: A total of 30 CT scans of the
shoulder were reformatted using OsiriX software multiplanar reconstruction. The
uncorrected (UNCORR) and corrected (CORR) CT scans were compared for measurements
of both (1) axial AP glenoid width and (2) glenoid version at 5 standardized
axial cuts. RESULTS: The mean difference in glenoid version was 2.6% (2 degrees
+/- 0.1 degrees ; P = .0222) and the mean difference in AP glenoid width was 5.2%
(1.2 +/- 0.42 mm; P = .0026) in comparing the CORR and UNCORR scans. The mean
angle of correction required to align the sagittal plane was 20.1 degrees of
rotation (range, 9 degrees -39 degrees ; standard error of mean, 1.2 degrees ).
CONCLUSION: These findings demonstrate that UNCORR CT scans of the glenohumeral
joint do not correct for the sagittal rotation of the glenoid, and this affects
the characteristics of the axial images. Failure to align the sagittal image to
the 12-o'clock to 6-o'clock axis results in measurement error in both glenoid
version and AP glenoid width. Use of UNCORR CT images may have notable
implications for decision-making and surgical treatment.
PMID- 26423024
TI - Multiple effect of social influence on cooperation in interdependent network
games.
AB - The social influence exists widely in the human society, where individual
decision-making process (from congressional election to electronic commerce) may
be affected by the attitude and behavior of others belonging to different social
networks. Here, we couple the snowdrift (SD) game and the prisoner's dilemma (PD)
game on two interdependent networks, where strategies in both games are
associated by social influence to mimick the majority rule. More accurately,
individuals' strategies updating refers to social learning (based on payoff
difference) and above-mentioned social influence (related with environment of
interdependent group), which is controlled by social influence strength s.
Setting s = 0 decouples the networks and returns the traditional network game;
while its increase involves the interactions between networks. By means of
numerous Monte Carlo simulations, we find that such a mechanism brings multiple
influence to the evolution of cooperation. Small s leads to unequal cooperation
level in both games, because social learning is still the main updating rule for
most players. Though intermediate and large s guarantees the synchronized
evolution of strategy pairs, cooperation finally dies out and reaches a
completely dominance in both cases. Interestingly, these observations are
attributed to the expansion of cooperation clusters. Our work may provide a new
understanding to the emergence of cooperation in intercorrelated social systems.
PMID- 26423025
TI - Management of gag reflex for patients undergoing dental treatment.
AB - BACKGROUND: Gag reflex is an involuntary defence mechanism to protect the pharynx
and throat from foreign objects. Gagging is a common problem encountered during
dental treatment, which makes therapeutic procedures distressing and often
difficult or even impossible to perform. Various interventions can be used to
control the gag reflex; for example, anti-nausea medicines, sedatives, local and
general anaesthetics, herbal remedies, behavioural therapies, acupressure,
acupuncture, and prosthetic devices. OBJECTIVES: To assess the effects of
pharmacological and non-pharmacological interventions for the management of
gagging in people undergoing dental treatment. SEARCH METHODS: We searched the
Cochrane Oral Health Group's Trials Register (to 7 April 2015), the Cochrane
Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 4,
2014), MEDLINE via OVID (1946 to 7 April 2015), EMBASE via OVID (1980 to 7 April
2015), CINAHL via EBSCO (1980 to 7 April 2015), AMED via OVID (1985 to 7 April
2015), IADR Conference Proceedings (online, 2001 to 7 April 2015), clinical trial
registries and Google search engine. SELECTION CRITERIA: We included randomised
controlled trials (RCTs), involving people who were given a pharmacological or
non-pharmacological intervention to manage gagging that interfered with dental
treatment. We excluded quasi-RCTs and cross-over trials. We excluded trials with
participants who had central or peripheral nervous system disorders; who had oral
lesions or were on systemic medications that might affect the gag sensation; or
had undergone surgery which might alter anatomy permanently. DATA COLLECTION AND
ANALYSIS: Two review authors independently selected trials. Three review authors
independently extracted data and assessed risk of bias in the included trials. We
estimated risk ratios (RRs) for dichotomous data, and mean differences (MDs) for
continuous data, with 95% confidence intervals (CIs). We assessed the overall
quality of the evidence using the GRADE approach. MAIN RESULTS: One RCT, a trial
on acupuncture at P6 (Pericardium 6 - situated on the anterior surface of wrist),
met the inclusion criteria. It included 33 adults who reported previous nausea
during dental procedures that hindered or prevented dental treatment from being
carried out properly. The trial was at unclear risk of bias. The outcome reported
in this trial was reduction in gagging. We obtained data for our primary outcome
(successful completion of dental procedure) by contacting the trial
author.Successful completion of dental procedure reported by the assessor showed
no difference in acupuncture at P6 group compared to sham acupuncture (RR 1.65,
95% CI 0.59 to 4.57). Reduction in gagging as reported by the assessor showed no
difference between acupuncture at P6 and sham acupuncture at any stage (stage 1:
MD 0.40, 95% CI -0.12 to 0.93; stage 2: MD 0.49, 95 % CI -0.26 to 1.24; stage 3:
MD 0.67, 95% CI -0.18 to 1.53). Reduction in gagging as reported by the
participant also showed no difference between acupuncture at P6 and sham
acupuncture (MD 0.86, 95% CI -1.13 to 2.85). The quality of the evidence for all
outcomes was very low.No noteworthy adverse effects were reported.We did not find
trials evaluating any other interventions used to manage gagging in people
undergoing dental treatment. AUTHORS' CONCLUSIONS: We found very low quality
evidence from a single trial that was insufficient to conclude if there is any
benefit of acupuncture in reducing gagging and allowing successful completion of
dental procedures. We did not find any evidence on any other interventions for
managing the gag reflex during dental treatment. More well-designed and well
reported trials evaluating different interventions are needed.
PMID- 26423026
TI - Natural small molecule FMHM inhibits lipopolysaccharide-induced inflammatory
response by promoting TRAF6 degradation via K48-linked polyubiquitination.
AB - TNF receptor-associated factor 6 (TRAF6) is a key hub protein involved in Toll
like receptor-dependent inflammatory signaling pathway, and it recruits
additional proteins to form multiprotein complexes capable of activating
downstream NF-kappaB inflammatory signaling pathway. Ubiquitin-proteasome system
(UPS) plays a crucial role in various protein degradations, such as TRAF6,
leading to inhibitory effects on inflammatory response and immunologic function.
However, whether ubiquitination-dependent TRAF6 degradation can be used as a
novel anti-inflammatory drug target still remains to be explored. FMHM, a
bioactive natural small molecule compound extracted from Chinese herbal medicine
Radix Polygalae, suppressed acute inflammatory response by targeting ubiquitin
protein and inducing UPS-dependent TRAF6 degradation mechanism. It was found that
FMHM targeted ubiquitin protein via Lys48 site directly induced Lys48 residue
linked polyubiquitination. This promoted Lys48 residue-linked polyubiquitin chain
formation on TRAF6, resulting in increased TRAF6 degradation via UPS and
inactivation of downstream NF-kappaB inflammatory pathway. Consequently, FMHM
down-regulated inflammatory mediator levels in circulation, protected multiple
organs against inflammatory injury in vivo, and prolong the survival of
endotoxemia mouse models. Therefore, FMHM can serve as a novel lead compound for
the development of TRAF6 scavenging agent via ubiquitination-dependent mode,
which represents a promising strategy for treating inflammatory diseases.
PMID- 26423027
TI - Unusual cause of lower extremity wounds: Cobb syndrome.
AB - Cobb syndrome (Cutaneomeningospinal Angiomatosis) is a rare segmental
neurocutaneous syndrome associated with metameric cutaneous and spinal cord
arteriovenous malformations (AVMs). In this syndrome, capillary malformation or
angiokeratoma-like lesions are formed in a dermatomal distribution, with an AVM
in the corresponding segment of the spinal cord. The spinal cord lesions can
cause neurological disorder and paraplegia, which typically develop during young
adulthood. We report a 32-year-old male with the Cobb syndrome associated with
lower extremity painful wounds and acute-onset paraplegia due to metameric
vascular malformations.
PMID- 26423028
TI - The Diarylprolinol Silyl Ethers: Ten Years After.
AB - Asymmetric organocatalysis has experienced an incredible development since the
beginning of this century. The expansion of the field has led to a large number
of efficient types of catalysts. One group, the diarylprolinol silyl ethers, was
introduced in 2005 and has been established as one of the most frequently used in
aminocatalysis. In this Minireview, we will take a look in the rear-view mirror,
ten years after the introduction of the diarylprolinol silyl ethers. We will
focus on the perspectives of the different activation modes made available by
this catalytic system. Starting with a short introduction to aminocatalysis, we
will outline the properties that have made the diarylprolinol silyl ethers a
common choice of catalyst. Furthermore, we will describe the major tendencies in
the activation and reaction concepts developed with regard to reactivity patterns
and combinations with other activation concepts.
PMID- 26423030
TI - Self-Running Liquid Metal Drops that Delaminate Metal Films at Record Velocities.
AB - This paper describes a new method to spontaneously accelerate droplets of liquid
metal (eutectic gallium indium, EGaIn) to extremely fast velocities through a
liquid medium and along predefined metallic paths. The droplet wets a thin metal
trace (a film ~100 nm thick, ~ 1 mm wide) and generates a force that
simultaneously delaminates the trace from the substrate (enhanced by spontaneous
electrochemical reactions) while accelerating the droplet along the trace. The
formation of a surface oxide on EGaIn prevents it from moving, but the use of an
acidic medium or application of a reducing bias to the trace continuously removes
the oxide skin to enable motion. The trace ultimately provides a sacrificial
pathway for the metal and provides a mm-scale mimic to the templates used to
guide molecular motors found in biology (e.g., actin filaments). The liquid metal
can accelerate along linear, curved and U-shaped traces as well as uphill on
surfaces inclined by 30 degrees. The droplets can accelerate through a viscous
medium up to 180 mm/sec which is almost double the highest reported speed for
self-running liquid metal droplets. The actuation of microscale objects found in
nature (e.g., cells, microorganisms) inspires new mechanisms, such as these, to
manipulate small objects. Droplets that are metallic may find additional
applications in reconfigurable circuits, optics, heat transfer elements, and
transient electronic circuits; the paper demonstrates the latter.
PMID- 26423029
TI - Glial activation in the periaqueductal gray promotes descending facilitation of
neuropathic pain through the p38 MAPK signaling pathway.
AB - The midbrain ventrolateral periaqueductal gray (VL-PAG) is a key component that
mediates pain modulation. Although spinal cord glial cells appear to play an
important role in chronic pain development, the precise mechanisms involving
descending facilitation pathways from the PAG following nerve injury are poorly
understood. This study shows that cellular events that occur during glial
activation in the VL-PAG may promote descending facilitation from the PAG during
neuropathic pain. Chronic constriction nerve injury (CCI) was induced by ligature
construction of the sciatic nerve in male Sprague-Dawley rats. Behavioral
responses to noxious mechanical (paw withdrawal threshold; PWT) and thermal (paw
withdrawal latency; PWL) stimuli were evaluated. After CCI, immunohistochemical
and Western blot analysis of microglia and astrocytes in the VL-PAG showed
morphological and quantitative changes indicative of activation in microglia and
astrocytes. Intra-VL-PAG injection of microglial or astrocytic inhibitors
attenuated PWT and PWL at days 7 and 14, respectively, following CCI. We also
evaluated the effects of intra-VL-PAG administration of the phosphorylated p38
mitogen-activated protein kinase (p-p38 MAPK) inhibitor SB 203580 at day 7 after
CCI. This treatment abolished microglial activation and produced a significant
time-dependent attenuation of PWT and PWL. Western blot analysis showed localized
expression of p-p38 in the VL-PAG after CCI. P-p38 was expressed in labeled
microglia of the VL-PAG but was not present in astrocytes and neurons on day 7
after CCI. These results demonstrate that CCI-induced neuropathic pain is
associated with glial activation in the VL-PAG, which likely participates in
descending pain facilitation through the p38 MAPK signaling pathway.
PMID- 26423031
TI - Gold-Catalyzed Benzylic Azidation of Phthalans and Isochromans and Subsequent
FeCl3-Catalyzed Nucleophilic Substitutions.
AB - The benzylic positions of the phthalan and isochroman derivatives (1) as benzene
fused cyclic ethers effectively underwent gold-catalyzed direct azidation using
trimethylsilylazide (TMSN3) to give the corresponding 1-azidated products (2)
possessing the N,O-acetal partial structure. The azido group of the N,O-acetal
behaved as a leaving group in the presence of catalytic iron(III) chloride, and 1
aryl or allyl phthalan and isochroman derivatives were obtained by nucleophilic
arylation or allylation, respectively. Meanwhile, a double nucleophilic
substitution toward the 1-azidated products (2) occurred at the 1-position using
indole derivatives as a nucleophile accompanied by elimination of the azido group
and subsequent ring opening of the cyclic ether nucleus produced the
bisindolylarylmethane derivatives.
PMID- 26423032
TI - A Reliable Method for the Separation and Detection of Synthetic Cannabinoids by
Supercritical Fluid Chromatography with Mass Spectrometry, and Its Application to
Plant Products.
AB - A reliable method using supercritical fluid chromatography with mass spectrometry
(SFC-MS) was developed for cannabinoids using compressed carbon dioxide (CO2) and
methanol as the mobile-phase. The cannabinoids, i.e., cannabicyclohexanol (CCH:
cis-isomer), trans-CCH, 5-(1,1-dimethylheptyl)-2-[(1R,3S)-3-hydroxycyclohexyl]
phenol (CP-47497), 5-(1,1-dimethylheptyl)-2-[(1R,2R,5R)-5-hydroxy-2-(3
hydroxypropyl)cyclohexyl]-phenol (CP-55940), 3-(1,1'-dimethylheptyl)
6aR,7,10,10aR-tetrahydro-1-hydroxy-6,6-dimethyl-6H-dibenzo[b,d]pyran-9-methanol
(HU-210), 2-[1R-3-methyl-6R-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3
benzenediol (CBD), (1-pentyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-018),
(1-butyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-073) and 1-(1-pentyl-1H
indol-3-yl)-2-(2-methoxyphenyl)-ethanone (JWH-250), were determined within 12 min
using a conventional column (2-EP) for SFC. Furthermore, two optical isomers of
CCH and trans-CCH were completely and rapidly separated by a chiral stationary
phase column (AMY1). A highly sensitive detection (0.002-3.75 ppb) was also
obtained by these methods using 2-EP and AMY1 columns. These methods were applied
to the qualitative and quantitative determination of cannabinoids in dried plant
products. Although the concentration and species were different in the products,
JWH-018, JWH-073 and CCH, including the cis-isomer, trans-isomer and the optical
isomers, were detected in the products. Therefore, the proposed SFC-MS method
seems to be useful as an alternative method to GC-MS and LC-MS for illegal drugs,
such as cannabinoids.
PMID- 26423033
TI - Reconstitution of L-Asparaginase in Siliconized Syringes with Shaking and
Headspace Air Induces Protein Aggregation.
AB - The aim of this study was to characterize protein aggregation during
reconstitution of a highly concentrated solution of lyophilized L-asparaginase (L
ASP). The effect of the preparation method on L-ASP aggregation using siliconized
or non-siliconized syringes and the effect of storage after preparation were
evaluated by far-UV circular dichroism spectroscopy, Raman microscopy, flow
cytometry, and flow particle image analysis. To investigate the effect of syringe
type in combination with shaking and headspace air on L-ASP aggregation, four
kinds of L-ASP in 5% glucose solutions were prepared (in the presence or absence
of silicon oil and headspace air). Slight differences in L-ASP secondary
structure were observed between the siliconized and non-siliconized syringe
systems before shaking. Large numbers of sub-visible (0.1-100 um) and submicron
(0.1-1 um) particles were formed by preparation with siliconized syringes and the
combination of shaking and headspace air. The number of aggregated particles was
not decreased with increased storage time. The Raman microscopy, flow cytometry
and flow particle image results suggested that L-ASP interacted with silicone
oil, which induced aggregation. Nevertheless, sub-visible and submicron particles
were also formed with non-siliconized syringes. However, using non-siliconized
syringes, the number of aggregated particles decreased with storage. No changes
in particle character were observed before or after shaking with headspace air in
non-siliconized syringes, indicating that soluble aggregates formed and dissolved
with storage. Silicone oil in syringes, in combination with shaking and headspace
air, strongly affected the aggregation of lyophilized L-ASP formulations during
preparation.
PMID- 26423035
TI - Effect of Process Parameters on Formation and Aggregation of Nanoparticles
Prepared with a Shirasu Porous Glass Membrane.
AB - The objectives of this study were to prepare itraconazole (ITZ) nanoparticles
using a Shirasu porous glass (SPG) membrane and to characterize the effects of
diverse preparation parameters on the physical stability of nanoparticles. SPG
membrane technology was used for the antisolvent precipitation method. The
preparation of nanoparticles was carried out over a wide range of continuous
phase factors (type of surfactant, surfactant concentration), dispersed-phase
factors (solvent type, solvent volume used to dissolve ITZ), and technical
factors (pressure, membrane pore size, stirring speed in the continuous phase,
temperature). Improved physical stability of nanoparticles was observed when
surfactant with a lower molecular weight and higher hydrophilic segment ratio was
used. The water miscibility of the solvent also had an effect on the physical
stability. N,N-Dimethylacetamide contributed to creating a well-rounded shape and
narrow size distribution due to high miscibility. Concentration of the surfactant
and solvent volume used for dissolving ITZ were related to instability of
nanoparticles, resulting from depletion attraction and Ostwald ripening. In
addition to these factors, technical factors changed the environment surrounding
ITZ nanoparticles, such as the physicochemical equilibrium between surfactant and
ITZ nanoparticles. Therefore, the appropriate continuous-phase factors, dispersed
phase factors, and technical factors should be maintained for stabilizing ITZ
nanoparticles.
PMID- 26423034
TI - Discovery of Novel Selective ERalpha/ERbeta Ligands by Multi-pharmacophore
Modeling and Virtual Screening.
AB - Estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) regulate
different sets of gene expression, and have different ligand responses, which
make the estrogen tissue-specific. Thus, the estrogen receptor (ER) subtype
selective ligands can improve the target-site selectivity and decrease the off
target effect. In order to discover the selective ER subtype ligands with novel
scaffolds, in this work three-dimensional (3D) pharmacophore models of the
ERalpha ligands (Hypo 1) and the ERbeta ligands (Hypo 2) were established
(correlation coefficients were 0.959 and 0.966) and validated (R=0.936 and 0.879;
enrichment factors (EFs) at 2% were 16.2 and 8.4; areas under the concentration
time curve (AUC) of the receiver operating curve (ROC) were 0.88 and 0.91) using
the Discovery Studio 4.0 software package. Hypo 1 and Hypo 2 were then employed
for virtual screening and ten hits were found as potential candidate leads. Based
on their ERalpha/ERbeta binding affinity results by fluorescence polarization
technology, two of these leads, AH-262/34334025 (AH) and AG-670/08803023 (AG)
with novel scaffolds were identified as selective ERalpha ligands. A molecular
docking study was also performed, which provided the explanation for the ER
subtype preferences for AH and AG.
PMID- 26423036
TI - Preparation and Evaluation of Newly Developed Chitosan Salt Coating Dispersions
for Colon Delivery without Requiring Overcoating.
AB - Although chitosan (CS) has been recognized as a good material for colon-specific
drug delivery systems, an overcoating with an enteric coating polymer on the
surface of CS is absolutely necessary because CS is soluble in acidic conditions
before reaching the colon. In the present study, to improve its stability in the
presence of acid, a newly developed CS-laurate (CS-LA) material was evaluated as
a coating dispersion for the development of colon-specific drug delivery systems.
Two types of CS with different molecular weights, CS250 and CS600, were used to
prepare CS-LA films by the casting method. The CS250-LA films had smooth
surfaces, whereas the surfaces of the CS600-LA films were rough, indicating that
the CS250-LA dispersion could form a denser film than CS600-LA. Both of these CS
LA films maintained a constant shape over 22 h in a pH 1.2 HCl/NaCl buffer, where
the corresponding CS films rapidly disintegrated. In addition, the CS250-LA film
showed specific colon degradability in a pH 6.0 phosphate buffered solution
containing 1.0% (w/v) beta-glucosidase. As a result of tensile strength and
elongation at the break, both CS-LA films were found to have flexible film
properties. Finally, the release of acetaminophen from disks coated with CS250-LA
dispersions was significantly suppressed in fluids at pH 1.2 and 6.8, whereas
disks coated with CS solution rapidly released the drug in pH 1.2 fluids. Taken
together, this study shows that LA modification could be a useful approach in
preparing CS films with acid stability and colonic degradability properties
without requiring overcoating.
PMID- 26423037
TI - Virtual Screening with Docking Simulations and Biochemical Evaluation of VHY
Phosphatase Inhibitors.
AB - Although VH1-related member Y (VHY) phosphatase is responsible for the
pathogenesis of neuroinflammatory diseases, no small-molecule inhibitor of VHY
has been reported so far. Here we first report eight VHY inhibitors identified
from molecular docking-based virtual screening and subsequent enzyme inhibition
assays. These inhibitors exhibit good biochemical potencies against VHY, with
associated IC50 values ranging from 1 to 9 uM. Because all these inhibitors were
also screened in silico for having desirable physicochemical properties as a drug
candidate, they deserve further investigation by structure-activity relationship
studies to develop new medicines for the treatment of neuroinflammatory diseases.
The structural features of VHY-inhibitor interactions relevant to the micromolar
level inhibitory activity are addressed in detail.
PMID- 26423038
TI - Synthesis and Antimicrobial Evaluation of Thieno[2,3-d]-pyrimidine,
Thieno[2',3':4,5]pyrimido[1,2-a][1,3,5]triazine, Thieno[2,3-d]-1,3-thiazine and
1,2,4-Triazole Systems.
AB - The reaction of lauroyl isothiocyanate with ethyl 2-amino-4,5,6,7
tetrahydrobenzo[b]thiophene-3-carboxylate gave ethyl 2-(3-dodecanoylthioureido)
4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 3. Compound 3 could serve as a
main building block in synthesis of the target heterocyclic systems like
thieno[2,3-d]-pyrimidine, thieno[2',3':4,5]pyrimido[1,2-a][1,3,5]triazine,
thieno[2,3-d]-1,3-thiazine and 1,2,4-triazole systems attached to the lauryl
group. The structures of the synthesized target heterocyclic compounds were
confirmed by microanalytical and spectral data. The antimicrobial activity of
some of the synthesized compounds was tested.
PMID- 26423039
TI - Clean Synthesis of N-Pyrrolyl Azoles by Metal-Free Oxidative Cross-Coupling Using
Recyclable Hypervalent Iodine Reagent.
AB - The facile and clean oxidative coupling reaction of pyrroles with azoles has been
achieved using the recyclable hypervalent iodine(III) reagents having adamantane
structures. These iodine(III) reagents could be recovered from the reaction
mixtures by a simple solid-liquid separation, i.e., filtration, for reuse.
PMID- 26423040
TI - Structural Optimization of Ghrelin Receptor Inverse Agonists to Improve
Lipophilicity and Avoid Mechanism-Based CYP3A4 Inactivation.
AB - Structural optimization of 2-aminonicotinamide derivatives as ghrelin receptor
inverse agonists is reported. So as to avoid mechanism-based inactivation (MBI)
of CYP3A4, 1,3-benzodioxol ring of the lead compound was modified. Improvement of
the main activity and lipophilicity was achieved simultaneously, leading to
compound 18a, which showed high lipophilic ligand efficiency (LLE) and low MBI
activity.
PMID- 26423041
TI - Novel Monoterpene Lactones from Cinnamomum inunctum.
AB - Four new monoterpene lactones, 5-(2,3-dihydroxy-3-methylbutyl)-4-hydroxy-4
methyldihydrofuran-2(3H)-one (1), 5-(2,3-dihydroxy-3-methylbutyl)-4-methylfuran
2(5H)-one (2), 8-hydroxy-4,7,7-trimethyl-1,6-dioxaspiro[4.4]non-3-en-2-one (3)
and 8-hydroxy-4,7,7-trimethyl-1,6-dioxaspiro[4.4]non-3-en-2-one (4), were
isolated from the methanolic extract of the fruit of Cinnamomum inunctum, a folk
medicine in Myanmar, together with a known compound, 3-hydroxy-4,4-dimethyl-4
butyrolactone (5). Their chemical structures were determined by spectral methods.
Among these, 3 and 4 possessed unique spirolactone moieties.
PMID- 26423042
TI - Antineuroinflammatory and Antiproliferative Activities of Constituents from Tilia
amurensis.
AB - As part of our ongoing search for bioactive constituents of natural Korean
medicinal resources, we found in a preliminary study that the methanol (MeOH)
extract from the trunks of Tilia amurensis RUPR. showed an inhibitory effect on
nitric oxide (NO) production in an activated murine microglial cell line. A
bioassay-guided fractionation and chemical investigation of the MeOH extract
resulted in the isolation and identification of a new isoflavonoid glycoside,
orobol 4'-O-beta-D-apiofuranosyl-(1->6)-beta-D-glucopyranoside (1) and 16 known
compounds (2-17). The structure of the new compound was determined by
spectroscopic methods, i.e., one-dimensional (1D) and two-dimensional (2D)-NMR
techniques and high resolution (HR)-MS, and chemical methods. The
antineuroinflammatory activities of the isolated compounds were determined by
measuring NO levels in the medium using murine microglial BV-2 cells. Among them,
12 compounds, including compound 1 (most active with an IC50 value of 23.42 uM),
inhibited NO production in lipopolysaccharide-stimulated BV-2 cells. Moreover,
compounds 1-4 showed moderate antiproliferative activities against the SK-MEL-2
cell line, with IC50 values ranging from 12.31 to 19.67 uM.
PMID- 26423043
TI - Saponins, Esculeosides B-1 and B-2, in Tomato Juice and Sapogenol, Esculeogenin
B1.
AB - It has been shown that commercial tomato juice packaged in 900 g plastic bottles
contains rare, naturally occurring steroidal solanocapsine-type tomato glycosides
in which the saponins consist of esculeosides B-1 (2) and B-2 (3) in 0.041% as
major components lacking esculeoside A. We suggest that these saponins are
derived from esculeoside A (1) when the juice in plastic bottles is prepared by
treatment with boiling water, similar to the process used in preparing canned
tomatoes. Herein, the obtained tomato saponins (2) and (3) provided sapogenols
esculeogenin B1 (4) and B2 (5), respectively, by acid hydrolysis. The former was
identical to esculeogenin B previously reported, and the latter was a new
sapogenol characterized to be (5alpha,22S,23S,25S)-22,26-epimino-16beta,23-epoxy
3beta,23,27-trihydroxycholestane.
PMID- 26423044
TI - A log-linear multidimensional Rasch model for capture-recapture.
AB - In this paper, a log-linear multidimensional Rasch model is proposed for capture
recapture analysis of registration data. In the model, heterogeneity of capture
probabilities is taken into account, and registrations are viewed as
dichotomously scored indicators of one or more latent variables that can account
for correlations among registrations. It is shown how the probability of a
generic capture profile is expressed under the log-linear multidimensional Rasch
model and how the parameters of the traditional log-linear model are derived from
those of the log-linear multidimensional Rasch model. Finally, an application of
the model to neural tube defects data is presented.
PMID- 26423045
TI - Efficient Light-Driven Water Oxidation Catalysis by Dinuclear Ruthenium
Complexes.
AB - Mastering the light-induced four-electron oxidation of water to molecular oxygen
is a key step towards the achievement of overall water splitting to produce
alternative solar fuels. In this work, we report two rugged molecular pyrazolate
based diruthenium complexes that efficiently catalyze visible-light-driven water
oxidation. These complexes were fully characterized both in the solid state (by X
ray diffraction analysis) and in solution (spectroscopically and
electrochemically). Benchmark performances for homogeneous oxygen production have
been obtained for both catalysts in the presence of a photosensitizer and a
sacrificial electron acceptor at pH 7, and a turnover frequency of up to 11.1 s(
1) and a turnover number of 5300 were obtained after three successive catalytic
runs. Under the same experimental conditions with the same setup, the pyrazolate
based diruthenium complexes outperform other well-known water oxidation catalysts
owing to both electrochemical and mechanistic aspects.
PMID- 26423046
TI - Botulinum toxin therapy for chronic anal fissures: where are we at currently?
AB - BACKGROUND: Botulinum toxin (Botox) injection for chronic anal fissure (CAF) is
commonly performed, yet there remains no consensus on optimal dosage or frequency
of injections required to achieve complete resolution of anal fissure. The aim of
this study was to determine the effectiveness of Botox and side-effect profile in
the management of CAF. METHODS: A retrospective clinical study of patients
between 2010 and 2014 who underwent a Botox injection for CAF at a tertiary
centre was performed. The effectiveness of Botox was measured using standardized
outcomes including overall healing rate, presence of anal pain, recurrence and
need for repeat botulinum injection. Binary outcomes were assessed using logistic
regression model. The analysis was performed using Stata version 13 (StataCorp,
College Station, TX, USA). RESULTS: One hundred and one patients underwent 126
Botox injections within the study period. The mean first post-operative visit was
at 1 month. The overall recurrence rate was 32%. The majority of patients were
given 33 U. No statistically significant relationship between dose and recurrence
was identified. The presence of pain at the first post-operative visit was a
predictor of future recurrence (odds ratio 3.92, confidence interval 1.58-9.74, P
= 0.003). CONCLUSION: Botox is an effective strategy for CAF. Low doses can be
given with good efficacy as highlighted by our audit and has the potential for
great cost saving. The best predictor of recurrence is the presence of pain at
the first post-procedure visit.
PMID- 26423047
TI - Detrimental effects of duplicate reads and low complexity regions on RNA- and
ChIP-seq data.
AB - BACKGROUND: Adapter trimming and removal of duplicate reads are common practices
in next-generation sequencing pipelines. Sequencing reads ambiguously mapped to
repetitive and low complexity regions can also be problematic for accurate
assessment of the biological signal, yet their impact on sequencing data has not
received much attention. We investigate how trimming the adapters, removing
duplicates, and filtering out reads overlapping low complexity regions influence
the significance of biological signal in RNA- and ChIP-seq experiments. METHODS:
We assessed the effect of data processing steps on the alignment statistics and
the functional enrichment analysis results of RNA- and ChIP-seq data. We compared
differentially processed RNA-seq data with matching microarray data on the same
patient samples to determine whether changes in pre-processing improved
correlation between the two. We have developed a simple tool to remove low
complexity regions, RepeatSoaker, available at
https://github.com/mdozmorov/RepeatSoaker, and tested its effect on the alignment
statistics and the results of the enrichment analyses. RESULTS: Both adapter
trimming and duplicate removal moderately improved the strength of biological
signals in RNA-seq and ChIP-seq data. Aggressive filtering of reads overlapping
with low complexity regions, as defined by RepeatMasker, further improved the
strength of biological signals, and the correlation between RNA-seq and
microarray gene expression data. CONCLUSIONS: Adapter trimming and duplicates
removal, coupled with filtering out reads overlapping low complexity regions, is
shown to increase the quality and reliability of detecting biological signals in
RNA-seq and ChIP-seq data.
PMID- 26423048
TI - Biofeedback therapy for chronic constipation in a patient with Prader-Willi
syndrome.
AB - Constipation is a common feature of Prader-Willi syndrome. Research exploring the
prevalence, cause and treatment options for constipation is limited and lacks
objective measurements such as anorectal manometry. We report a case of a 16-year
old lady with Prader-Willi syndrome presenting with rectal pain and constipation
for 2 years despite multiple medications and weekly enemas. She also noted
passive fecal incontinence that required frequent manual disimpactions. Anorectal
manometry revealed an abnormal relaxation of the puborectalis and external
sphincter muscles on push maneuvers suggesting dyssynergic defecation and rectal
hypersensitivity. Contraction and relaxation of her pelvic muscles were recorded
with electromyography. Relaxation of the puborectalis muscle improved
significantly after three biofeedback sessions. Patient was successfully tapered
off laxatives and has been maintained on linaclotide only. Dyssynergic defecation
may be a common finding in Prader-Willi syndrome. In selected cases we recommend
anorectal manometry to identify neuromuscular dysfunction and subsequent
biofeedback therapy depending on the degree of mental retardation to minimize
overuse of laxatives.
PMID- 26423049
TI - A qualitative assessment of health extension workers' relationships with the
community and health sector in Ethiopia: opportunities for enhancing maternal
health performance.
AB - BACKGROUND: Health extension workers (HEWs) in Ethiopia have a unique position,
connecting communities to the health sector. This intermediary position requires
strong interpersonal relationships with actors in both the community and health
sector, in order to enhance HEW performance. This study aimed to understand how
relationships between HEWs, the community and health sector were shaped, in order
to inform policy on optimizing HEW performance in providing maternal health
services. METHODS: We conducted a qualitative study in six districts in the
Sidama zone, which included focus group discussions (FGDs) with HEWs, women and
men from the community and semi-structured interviews with HEWs; key informants
working in programme management, health service delivery and supervision of HEWs;
mothers; and traditional birth attendants. Respondents were asked about
facilitators and barriers regarding HEWs' relationships with the community and
health sector. Interviews and FGDs were recorded, transcribed, translated, coded
and thematically analysed. RESULTS: HEWs were selected by their communities,
which enhanced trust and engagement between them. Relationships were facilitated
by programme design elements related to support, referral, supervision, training,
monitoring and accountability. Trust, communication and dialogue and expectations
influenced the strength of relationships. From the community side, the health
development army supported HEWs in liaising with community members. From the
health sector side, top-down supervision and inadequate training possibilities
hampered relationships and demotivated HEWs. Health professionals,
administrators, HEWs and communities occasionally met to monitor HEW and
programme performance. Expectations from the community and health sector
regarding HEWs' tasks sometimes differed, negatively affecting motivation and
satisfaction of HEWs. CONCLUSION: HEWs' relationships with the community and
health sector can be constrained as a result of inadequate support systems, lack
of trust, communication and dialogue and differing expectations. Clearly defined
roles at all levels and standardized support, monitoring and accountability,
referral, supervision and training, which are executed regularly with clear
communication lines, could improve dialogue and trust between HEWs and actors
from the community and health sector. This is important to increase HEW
performance and maximize the value of HEWs' unique position.
PMID- 26423050
TI - Effect of local anesthetic concentration, dose and volume on the duration of
single-injection ultrasound-guided axillary brachial plexus block with
mepivacaine: a randomized controlled trial.
AB - BACKGROUND: In what way volume, concentration and dose affect block duration is
controversial. The purpose of the present study is to investigate the effect of
dose, volume and concentration of mepivacaine on the duration of sensory and
motor blockade in ultrasound-guided single shot axillary brachial plexus
blockade. METHODS: In this parallel group randomized trial conducted in the Sint
Maartenskliniek Nijmegen, 45 adult patients undergoing minor orthopaedic forearm,
wrist or hand surgery were randomized to 3 groups. Group A: 20 mL mepivacaine 1.5
%, Group B: 30 mL mepivacaine 1 % and Group C: 30 mL mepivacaine 1.5 %.
Randomization was computer-generated, with allocation concealment by opaque
sequentially numbered sealed envelopes. Patients and observers were blinded to
group allocation. PRIMARY OUTCOME MEASURE: duration of sensory block. RESULTS:
Forty-five patients were randomized, four patients were excluded and replaced,
and 15 patients in each group were included in the analysis. Mean (95 % CI)
sensory and motor block duration was 256 (230-282) and 254 (226-282) minutes in
Group A, 226 (209-243) and 220 (200-240) minutes in Group B and 270 (249-291) and
264 (244-284) minutes in Group C. Duration of sensory and motor block duration
differed significantly between groups (p = 0.012 and p = 0.016 respectively).
Post-hoc analysis showed a significantly reduced sensory and motor block duration
in Group B when compared to Group C of 44 min. No local anesthetic systemic
toxicity was reported. CONCLUSIONS: When using mepivacaine for axillary brachial
plexus block, a higher dose and concentration was associated with a longer
duration of sensory and motor blockade, but not a higher volume. TRIAL
REGISTRATION: The Netherlands National Trial Register NTR3648 . Registered
October 3, 2012.
PMID- 26423051
TI - The role of social networks in the development of overweight and obesity among
adults: a scoping review.
AB - BACKGROUND: Although it is increasingly acknowledged that social networks are
important to our understanding ofoverweight and obesity, there is limited
understanding about the processes by which such networks shapetheir progression.
This paper reports the findings of a scoping review of the literature that sought
to identify the key processes through which social networks are understood to
influence the development of overweight and obesity. METHODS: A scoping review
was conducted. Forty five papers were included in the final review, the findings
of which were synthesised to provide an overview of the main processes through
which networks have been understood to influence the development of overweight
and obesity. RESULTS: Included papers addressed a wide range of research
questions framed around six types of networks: a paired network (one's spouse or
intimate partner); friends and family (including work colleagues and people
within social clubs); ephemeral networks in shared public spaces (such as fellow
shoppers in a supermarket or diners in a restaurant); people living within the
same geographical region; peers (including co-workers, fellow students, fellow
participants in a weight loss programme); and cultural groups (often related
toethnicity). As individuals are embedded in many of these different types of
social networks at any one time, the pathways of influence from social networks
to the development of patterns of overweight and obesity are likely to be complex
and interrelated. Included papers addressed a diverse set of issues: body weight
trends over time; body size norms or preferences; weight loss and management;
physical activity patterns; and dietary patterns. DISCUSSION: Three inter-related
processes were identified: social contagion (whereby the network in which people
are embedded influences their weight or weight influencing behaviours), social
capital (whereby sense of belonging and social support influence weight or weight
influencing behaviours), and social selection (whereby a person's network might
develop according to his or her weight). CONCLUSIONS: The findings have important
implications for understanding about methods to target the spread of obesity,
indicating that much greater attention needs to be paid to the social context in
which people make decisions about their weight and weight influencing behaviours.
PMID- 26423052
TI - Molecular analysis of clinical isolates previously diagnosed as Mycobacterium
intracellulare reveals incidental findings of "Mycobacterium indicus pranii"
genotypes in human lung infection.
AB - BACKGROUND: Mycobacterium intracellulare is a major cause of Mycobacterium avium
complex lung disease in many countries. Molecular studies have revealed several
new Mycobacteria species that are closely related to M. intracellulare. The aim
of this study was to re-identify and characterize clinical isolates from patients
previously diagnosed with M. intracellulare lung disease at the molecular level.
METHODS: Mycobacterial isolates from 77 patients, initially diagnosed with M.
intracellulare lung disease were re-analyzed by multi-locus sequencing and
pattern of insertion sequences. RESULTS: Among the 77 isolates, 74 (96 %)
isolates were designated as M. intracellulare based on multigene sequence-based
analysis. Interestingly, the three remaining strains (4 %) were re-identified as
"Mycobacterium indicus pranii" according to distinct molecular phylogenetic
positions in rpoB and hsp65 sequence-based typing. In hsp65 sequevar analysis,
code 13 was found in the majority of cases and three unreported codes were
identified. In 16S-23S rRNA internal transcribed spacer (ITS) sequevar analysis,
all isolates of both species were classified within the Min-A ITS sequevar.
Interestingly, four of the M. intracellulare isolates harbored IS1311, a M. avium
specific element. Two of three patients infected with "M. indicus pranii" had
persistent positive sputum cultures after antibiotic therapy, indicating the
clinical relevance of this study. CONCLUSIONS: This analysis highlights the
importance of precise identification of clinical isolates genetically close to
Mycobacterium species, and suggests that greater attention should be paid to
nontuberculous mycobacteria lung disease caused by "M. indicus pranii".
PMID- 26423054
TI - Is patellar denervation necessary in total knee arthroplasty without patellar
resurfacing?
AB - PURPOSE: To conduct a meta-analysis with randomized controlled trials (RCTs)
published in full text to determine the effectiveness of patellar denervation
(PD) in primary total knee arthroplasty (TKA). METHODS: Literature search was
performed in PubMed, Embase, Web of Science and Cochrane Library for information
from the earliest date of data collection to February 2015. RCTs comparing the
benefits and risks of PD with those of no patellar denervation (NPD) in primary
TKAs were included. Statistical heterogeneity was quantitatively evaluated by
X(2) test with the significance set P < 0.10 or I (2) > 50 %. RESULTS: Six RCTs
consisting of 751 patients were included. The incidences of AKP in PD group and
NPD group were 38.3 % (90/235) and 46.3 % (107/231), respectively. Meta-analysis
showed significant prevention effect of PD on the incidence of AKP (OR 0.65; 95 %
CI 0.42, 1.00; P = 0.05) without significant heterogeneity (I (2) = 44 %, P =
0.15). Our results also indicated that PD was significantly associated with
better American Knee Society knee (WMD = 2.50; 95 % CI 0.34, 4.67; P = 0.02) and
functional scores (WMD = 4.07; 95 % CI 1.34, 6.80; P = 0.0003) and range of
motion (ROM) (WMD = 4.27; 95 % CI 1.95, 6.60; P = 0.0003) compared with NPD.
However, there was no significant difference between the two groups no matter in
Oxford knee score, patellar score or visual analogue scale at any other time.
Complications and revisions did not differ significantly between the two groups.
CONCLUSION: This meta-analysis showed that PD in TKAs without patellar
resurfacing, compared with NPD, could prevent the incidence of post-operative AKP
and improve clinical outcome in KSS and post-operative ROM. Based on the above
results, PD was a safe procedure with no significant complications and revision
or re-operations. LEVEL OF EVIDENCE: Therapeutic study, Level II.
PMID- 26423056
TI - Editorial: Colorectal Cancer Screening Education in Medically Vulnerable
Populations: the Role of the Journal of Cancer Education.
PMID- 26423055
TI - Total knee arthroplasty after failed high tibial osteotomy: a systematic review
of open versus closed wedge osteotomy.
AB - PURPOSE: Medial opening wedge high tibial osteotomy (HTO) has become increasingly
popular as an alternative to lateral closing wedge osteotomy for the treatment of
medial compartment knee osteoarthritis with varus deformity. The present
systematic review was conducted to provide an objective analysis of total knee
arthroplasty (TKA) outcomes following previous knee osteotomy (medial opening
wedge vs. lateral closing wedge). METHODS: A literature search of online
databases (MEDLINE, EMBASE, Cochrane Library database) was made, in addition to
manual search of major orthopaedic journals. The methodological quality of each
of the studies was assessed on the Newcastle-Ottawa Scale and Effective Practice
and Organization of Care. A total of ten studies were included in the review.
There were eight studies with Level IV and two studies with Level III evidence.
RESULTS: Eight studies reported clinical and radiologic scores. Comparative
studies between TKA following medial opening and lateral closing wedge HTO did
not demonstrate statistically significant clinical and radiologic differences.
The revision rates were similar. However, more technical issues during TKA
surgery after lateral closing wedge HTO were mentioned than the medial open wedge
group. The quadriceps snip, tibial tubercle osteotomy, and lateral soft tissue
release were more frequently needed in the lateral closing wedge HTO group. In
addition, because of loss of proximal tibia bone geometry in the lateral closing
wedge HTO group, concerns such as tibia stem impingement in the lateral tibial
cortex was noted. CONCLUSION: The present systematic review suggests that TKA
after medial opening and lateral closing wedge HTO showed similar performance.
Clinical and radiologic outcome including revision rates did not statistically
differ from included studies. However, there are more surgical technical concerns
in TKA conversion from lateral closing wedge HTO than from the medial opening
wedge HTO group. LEVEL OF EVIDENCE: IV.
PMID- 26423053
TI - Concept and design of a genome-wide association genotyping array tailored for
transplantation-specific studies.
AB - BACKGROUND: In addition to HLA genetic incompatibility, non-HLA difference
between donor and recipients of transplantation leading to allograft rejection
are now becoming evident. We aimed to create a unique genome-wide platform to
facilitate genomic research studies in transplant-related studies. We designed a
genome-wide genotyping tool based on the most recent human genomic reference
datasets, and included customization for known and potentially relevant metabolic
and pharmacological loci relevant to transplantation. METHODS: We describe here
the design and implementation of a customized genome-wide genotyping array, the
'TxArray', comprising approximately 782,000 markers with tailored content for
deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci
important in transplantation. To test concordance and genotyping quality, we
genotyped 85 HapMap samples on the array, including eight trios. RESULTS: We show
low Mendelian error rates and high concordance rates for HapMap samples (average
parent-parent-child heritability of 0.997, and concordance of 0.996). We
performed genotype imputation across autosomal regions, masking directly
genotyped SNPs to assess imputation accuracy and report an accuracy of >0.962 for
directly genotyped SNPs. We demonstrate much higher capture of the natural killer
cell immunoglobulin-like receptor (KIR) region versus comparable platforms.
Overall, we show that the genotyping quality and coverage of the TxArray is very
high when compared to reference samples and to other genome-wide genotyping
platforms. CONCLUSIONS: We have designed a comprehensive genome-wide genotyping
tool which enables accurate association testing and imputation of ungenotyped
SNPs, facilitating powerful and cost-effective large-scale genotyping of
transplant-related studies.
PMID- 26423057
TI - The Evolution of Undergraduate Medical Student Research Activities: Personal
Experience of a Developing Nation's Uprise.
PMID- 26423058
TI - Web-Based Study for Improving Mammography Among Korean American Women.
AB - Web-based culture-specific interventions for Korean American (KA) women to
improve mammography utilization are not available. An established intervention
developed to improve mammography utilizations for Korean American (KA) women was
tested via the Web for its efficacy, feasibility, and acceptability. A randomized
controlled trial, with a pretest-posttest control group design, was conducted
with 136 KA women and their spouses. Intention to have a mammogram within the
next 12 months increased significantly in the intervention group compare to
controls. Among women whose mammograms had not been updated, 22 % of women in the
intervention and 13 % of women in the control group obtained a mammogram at 2
month post-baseline, even though the difference was not statistically
significant. The Web-based study educating couples was feasible and could improve
KA women's breast cancer screening intention and behaviors. Combining off-line
contact for recruitment/data collection with online intervention material could
decrease the attrition rate in the future study because the attrition rate in
this study was higher than the original study.
PMID- 26423059
TI - Oral Cancer: Awareness and Knowledge Among Dental Patients in Riyadh.
AB - More than 50 % of oral cancer cases are diagnosed at advanced stages. Public
knowledge about oral cancer can help in prevention and early detection of the
disease. The aim of the present study was to assess the levels of awareness and
knowledge about signs and risk factors of oral cancer among dental patients in
Saudi Arabia. A self-administered questionnaire was used to collect information
from 1410 randomly selected patients attending dental departments within public
hospitals in Riyadh, Saudi Arabia. The collected data were analyzed using SPSS
software. The significance level was set at P < 0.05. The study revealed that
only 62.4 % were aware of oral cancer. Some 68.2 and 56.5 %, respectively, were
able to correctly identify tobacco and alcohol as risk factors. More than two
thirds of subjects had no knowledge about any signs of oral cancer. Participants
with lower than university education were significantly less aware, and had much
less knowledge, of the signs and risk factors of oral cancer. The knowledge
regarding oral cancer among Saudi dental patients is alarmingly low.
Interventions to improve public knowledge about oral cancer and attitudes towards
early diagnosis and treatment are urgently indicated.
PMID- 26423060
TI - Laparoscopic surgery of benign entero-vesical or entero-vaginal fistulae.
AB - PURPOSE: Entero-vesical or entero-vaginal fistulae (EVF) are an uncommon septic
complication mainly of diverticular disease. The fistulae are usually situated
within extensive and dense inflammatory masses occluding the entrance of the
pelvis. There are still some controversies regarding laparoscopic feasibility and
treatment modalities of this disorder. METHODS: A retrospective chart review of
all patients with EVF operated at our department since 2008. Patients were
identified by use of the computerized hospital information system. RESULTS: In
nineteen patients (ten males), median age 68 years, 13 patients had entero
vesical fistulae, and 6 patients had entero-vaginal fistulae. The fistulae were
caused by complicated diverticular disease in 16 patients (84 %), Crohn's disease
(two patients), and ulcerative colitis (one patient). All cases were attempted
laparoscopically. Operative treatment involved separation of the inflammatory
mass and resection of the affected colorectal segment. There were three
conversions (16 %), all three requiring bladder repair considered too extensive
for laparoscopic means. In two further patients small bladder defects were
sutured laparoscopically, the remaining patients required no bladder repair. The
inferior mesentric artery (IMA) was preserved in all cases. Median operative time
was 180 min. Two patients received a protective ileostomy: one converted patient
and one cachectic patient with Crohn's disease under immune-modulating therapy.
Both ileostomies were closed. Altogether, there were five complications in five
patients (26 %), four of them were minor (Clavien grade I and II). The cachectic
patient with Crohn's disease suffered a major (grade IIIb) complication (stoma
prolapse, treated by early closure of the ileostomy). There was no anastomotic
leakage and no mortality. Median hospital stay was 12 days. CONCLUSIONS: The
laparoscopic approach is a safe option for the treatment of EVF of benign
inflammatory origin. In most cases it offers all the advantages pertaining to
minimally invasive surgery. For a definite and causal approach, the disorder
belongs primarily within the therapeutic domain of the visceral surgeon.
Following the separation of the inflammatory colon, most of the bladder lesions
caused by EVF will heal without further surgical measures.
PMID- 26423061
TI - Dulaglutide: A Review in Type 2 Diabetes.
AB - Dulaglutide (TrulicityTM) is a once-weekly subcutaneously administered glucagon
like peptide-1 (GLP-1) receptor agonist produced by recombinant DNA technology
and approved in numerous countries as an adjunct to diet and exercise for the
treatment of adults with type 2 diabetes (T2DM). In randomized controlled trials
in patients with T2DM, dulaglutide monotherapy was noninferior to once-daily
subcutaneous liraglutide monotherapy and significantly more effective than oral
metformin monotherapy in improving glycemic control at 26 weeks. When used in
combination with other agents (including metformin, metformin and a sulfonylurea,
metformin and oral pioglitazone, and prandial insulin +/- metformin), dulaglutide
was noninferior to once-daily liraglutide and significantly more effective than
once-daily oral sitagliptin, twice-daily subcutaneous exenatide, and once-daily
subcutaneous insulin glargine in terms of improvements in glycated hemoglobin
from baseline at 26 or 52 weeks, in trials of 26-104 weeks' duration. Moreover,
dulaglutide 1.5 mg once weekly, but not 0.75 mg once weekly, was associated with
consistent reductions form baseline in bodyweight. Improvements in glycemic
control and bodyweight were maintained during long-term treatment (up to 2
years). Dulaglutide was generally well tolerated, with a low inherent risk of
hypoglycemia. The most frequently reported adverse events in clinical trials were
gastrointestinal-related (e.g., nausea, vomiting, and diarrhea). Thus,
dulaglutide is a useful option for the treatment of adult patients with T2DM.
PMID- 26423063
TI - 'Predatory' open access: a longitudinal study of article volumes and market
characteristics.
AB - BACKGROUND: A negative consequence of the rapid growth of scholarly open access
publishing funded by article processing charges is the emergence of publishers
and journals with highly questionable marketing and peer review practices. These
so-called predatory publishers are causing unfounded negative publicity for open
access publishing in general. Reports about this branch of e-business have so far
mainly concentrated on exposing lacking peer review and scandals involving
publishers and journals. There is a lack of comprehensive studies about several
aspects of this phenomenon, including extent and regional distribution. METHODS:
After an initial scan of all predatory publishers and journals included in the so
called Beall's list, a sample of 613 journals was constructed using a stratified
sampling method from the total of over 11,000 journals identified. Information
about the subject field, country of publisher, article processing charge and
article volumes published between 2010 and 2014 were manually collected from the
journal websites. For a subset of journals, individual articles were sampled in
order to study the country affiliation of authors and the publication delays.
RESULTS: Over the studied period, predatory journals have rapidly increased their
publication volumes from 53,000 in 2010 to an estimated 420,000 articles in 2014,
published by around 8,000 active journals. Early on, publishers with more than
100 journals dominated the market, but since 2012 publishers in the 10-99 journal
size category have captured the largest market share. The regional distribution
of both the publisher's country and authorship is highly skewed, in particular
Asia and Africa contributed three quarters of authors. Authors paid an average
article processing charge of 178 USD per article for articles typically published
within 2 to 3 months of submission. CONCLUSIONS: Despite a total number of
journals and publishing volumes comparable to respectable (indexed by the
Directory of Open Access Journals) open access journals, the problem of predatory
open access seems highly contained to just a few countries, where the academic
evaluation practices strongly favor international publication, but without
further quality checks.
PMID- 26423064
TI - Ramakrishna and the Clinic of Paradox.
AB - This study presents a clinical conception of the human being as the paradox
between immanence and transcendence. Through an exposition of the clinical
conceptions of Brazilian author Gilberto Safra, we search for an integral manner
in which to understand mystical experience as a way to rethink the ontological
conceptions inherent to clinical practice. In such perspective, we elaborate a
critique of both the psychological-only approach to mystical experience as well
as the spiritual-only approach. We present it through the life of Indian mystic
Ramakrishna, by comparing the interpretation different authors make of his
experiences and placing our own perspective.
PMID- 26423065
TI - Assessing Age Differences in the Relationship Between Emotional Support and
Health Among Older Mexican Americans.
AB - Research reveals that people tend to place greater value on emotional support as
they move through the life course. Older people are likely to do so because
emotional support benefits them in some way. The purpose of this study was to see
whether there are age differences in the relationship between emotional support
and the number of chronic health conditions. In the process, an effort is made to
contribute to the literature in three ways. First, an emphasis placed on
assessing the relationship between emotional support and health within late life.
Second, variations in the source of support are taken into account by contrasting
support within religious institutions with support that is received outside
church. Third, these issues are examined with data provided by a nationally
representative sample of older Mexican Americans (N = 663). The findings suggest
that age differences in the relationship between emotional support and health are
present within late life. Moreover, the data indicate that this relationship
holds for church-based social support but not support that is received outside
the church.
PMID- 26423066
TI - Sex differences in the shoulder joint position sense acuity: a cross-sectional
study.
AB - BACKGROUND: Work-related musculoskeletal disorders (WMSD) is the most expensive
form of work disability. Female sex has been considered as an individual risk
factor for the development of WMSD, specifically in the neck and shoulder region.
One of the factors that might contribute to the higher injury rate in women is
possible differences in neuromuscular control. Accordingly the purpose of this
study was to estimate the effect of sex on shoulder joint position sense acuity
(as a part of shoulder neuromuscular control) in healthy individuals. METHODS:
Twenty-eight healthy participants, 14 females and 14 males were recruited for
this study. To test position sense acuity, subjects were asked to flex their
dominant shoulder to one of the three pre-defined angle ranges (low, mid and high
ranges) with eyes closed, hold their arm in that position for three seconds, go
back to the starting position and then immediately replicate the same joint
flexion angle, while the difference between the reproduced and original angle was
taken as the measure of position sense error. The errors were measured using
Vicon motion capture system. Subjects reproduced nine positions in total (3
ranges * 3 trials each). RESULTS: Calculation of absolute repositioning error
(magnitude of error) showed no significant difference between men and women (p
value >= 0.05). However, the analysis of the direction of error (constant error)
showed a significant difference between the sexes, as women tended to mostly
overestimate the target, whereas men tended to both overestimate and
underestimate the target (p-value <= 0.01, observed power = 0.79). The results
also showed that men had a significantly more variable error, indicating more
variability in their position sense, compared to women (p-value <= 0.05, observed
power = 0.78). DISCUSSION: Differences observed in the constant JPS error suggest
that men and women might use different neuromuscular control strategies in the
upper limb. In addition, higher JPS variability observed in men might be one of
the factors that could contribute to their lower rate of musculoskeletal
disorders, compared to women. CONCLUSIONS: The result of this study showed that
shoulder position sense, as part of the neuromuscular control system, differs
between men and women. This finding can help us better understand the reasons
behind the higher rate of musculoskeletal disorders in women, especially in the
working environments.
PMID- 26423067
TI - Structural features of conopeptide genes inferred from partial sequences of the
Conus tribblei genome.
AB - The evolvability of venom components (in particular, the gene-encoded peptide
toxins) in venomous species serves as an adaptive strategy allowing them to
target new prey types or respond to changes in the prey field. The structure,
organization, and expression of the venom peptide genes may provide insights into
the molecular mechanisms that drive the evolution of such genes. Conus is a
particularly interesting group given the high chemical diversity of their venom
peptides, and the rapid evolution of the conopeptide-encoding genes. Conus
genomes, however, are large and characterized by a high proportion of repetitive
sequences. As a result, the structure and organization of conopeptide genes have
remained poorly known. In this study, a survey of the genome of Conus tribblei
was undertaken to address this gap. A partial assembly of C. tribblei genome was
generated; the assembly, though consisting of a large number of fragments,
accounted for 2160.5 Mb of sequence. A large number of repetitive genomic
elements consisting of 642.6 Mb of retrotransposable elements, simple repeats,
and novel interspersed repeats were observed. We characterized the structural
organization and distribution of conotoxin genes in the genome. A significant
number of conopeptide genes (estimated to be between 148 and 193) belonging to
different superfamilies with complete or nearly complete exon regions were
observed, ~60 % of which were expressed. The unexpressed conopeptide genes
represent hidden but significant conotoxin diversity. The conotoxin genes also
differed in the frequency and length of the introns. The interruption of exons by
long introns in the conopeptide genes and the presence of repeats in the introns
may indicate the importance of introns in facilitating recombination, evolution
and diversification of conotoxins. These findings advance our understanding of
the structural framework that promotes the gene-level molecular evolution of
venom peptides.
PMID- 26423068
TI - High reactive oxygen species levels are detected at the end of the chronological
life span of translocant yeast cells.
AB - Chromosome translocation is a major genomic event for a cell, affecting almost
every of its life aspects ranging from metabolism, organelle maintenance and
homeostasis to gene maintenance and expression. By using the bridge-induced
translocation system, we defined the effects of induced chromosome translocation
on the chronological life span (CLS) of yeast with particular interest to the
oxidative stress condition. The results demonstrate that every translocant strain
has a different CLS, but all have a high increase in reactive oxygen species and
in lipid peroxides levels at the end of the life span. This could be due to the
very unique and strong deregulation of the oxidative stress network. Furthermore,
the loss of the translocated chromosome occurs at the end of the life span and is
locus dependent. Additionally, the RDH54 gene may play a role in the correct
segregation of the translocant chromosome, since in its absence there is an
increase in loss of the bridge-induced translocated chromosome.
PMID- 26423069
TI - GDSL esterase/lipase genes in Brassica rapa L.: genome-wide identification and
expression analysis.
AB - GDSL esterase/lipase proteins (GELPs), a very large subfamily of lipolytic
enzymes, have been identified in microbes and many plants, but only a few have
been characterized with respect to their roles in growth, development, and stress
responses. In Brassica crops, as in many other species, genome-wide systematic
analysis and functional studies of these genes are still lacking. As a first step
to study their function in B. rapa ssp. pekinensis (Chinese cabbage), we
comprehensively identified all GELP genes in the genome. We found a total of 121
Brassica rapa GDSL esterase/lipase protein genes (BrGELPs), forming three clades
in the phylogenetic analysis (two major and one minor), with an asymmetrical
chromosomal distribution. Most BrGELPs possess four strictly conserved residues
(Ser-Gly-Asn-His) in four separate conserved regions, along with short conserved
and clade-specific blocks, suggesting functional diversification of these
proteins. Detailed expression profiling revealed that BrGELPs were expressed in
various tissues, including floral organs, implying that BrGELPs play diverse
roles in various tissues and during development. Ten percent of BrGELPs were
specifically expressed in fertile buds, rather than male-sterile buds, implying
their involvement in pollen development. Analyses of EXL6 (extracellular lipase
6) expression and its co-expressed genes in both B. rapa and Arabidopsis, as well
as knockdown of this gene in Arabidopsis, revealed that this gene plays an
important role in pollen development in both species. The data described in this
study will facilitate future investigations of other BrGELP functions.
PMID- 26423070
TI - Colour learning when foraging for nectar and pollen: bees learn two colours at
once.
AB - Bees are model organisms for the study of learning and memory, yet nearly all
such research to date has used a single reward, nectar. Many bees collect both
nectar (carbohydrates) and pollen (protein) on a single foraging bout, sometimes
from different plant species. We tested whether individual bumblebees could learn
colour associations with nectar and pollen rewards simultaneously in a foraging
scenario where one floral type offered only nectar and the other only pollen. We
found that bees readily learned multiple reward-colour associations, and when
presented with novel floral targets generalized to colours similar to those
trained for each reward type. These results expand the ecological significance of
work on bee learning and raise new questions regarding the cognitive ecology of
pollination.
PMID- 26423071
TI - Low BIK outside-inside-out interactive inflammation immune-induced transcription
dependent apoptosis through FUT3-PMM2-SQSTM1-SFN-ZNF384.
AB - Eighteen different Pearson mutual-positive-correlation BIK-activatory molecular
feedback upstream and downstream networks were constructed from 79 overlapping of
376 GRNInfer and 98 Pearson under BIK CC >= 0.25 in low normal adjacent tissues
of Taiwan compared with high lung adenocarcinoma. Our identified BIK interactive
total feedback molecular network showed FUT3 [fucosyltransferase 3 (galactoside
3(4)-L-fucosyltransferase Lewis blood group)], PMM2 (phosphomannomutase 2),
SQSTM1 (sequestosome 1), SFN_2 [REX2 RNA exonuclease 2 homolog (S. cerevisiae)]
and ZNF384 (zinc finger protein 384) in low normal adjacent tissues of lung
adenocarcinoma. BIK interactive total feedback terms included mitochondrial
envelope, endomembrane system, integral to membrane, Golgi apparatus, cytoplasm,
nucleus, cytosol, intracellular signaling cascade, mitochondrion, extracellular
space, inflammation, immune response, apoptosis, cell differentiation, cell
cycle, regulation of cell cycle, cell proliferation, estrogen-responsive protein
Efp controls cell cycle and breast tumors growth, induction or regulation of
apoptosis based on integrative GO, KEGG, GenMAPP, BioCarta and disease databases
in low normal adjacent tissues of lung adenocarcinoma. Therefore, we propose low
BIK outside-inside-out interactive inflammation immune-induced transcription
dependent apoptosis through FUT3-PMM2-SQSTM1-SFN-ZNF384 in normal adjacent
tissues of lung adenocarcinoma.
PMID- 26423073
TI - In-Situ Remediation Approaches for the Management of Contaminated Sites: A
Comprehensive Overview.
AB - Though several in-situ treatment methods exist to remediate polluted sites,
selecting an appropriate site-specific remediation technology is challenging and
is critical for successful clean up of polluted sites. Hence, a comprehensive
overview of all the available remediation technologies to date is necessary to
choose the right technology for an anticipated pollutant. This review has
critically evaluated the (i) technological profile of existing in-situ
remediation approaches for priority and emerging pollutants, (ii) recent
innovative technologies for on-site pollutant remediation, and (iii) current
challenges as well as future prospects for developing innovative approaches to
enhance the efficacy of remediation at contaminated sites.
PMID- 26423072
TI - Prognostic implications of heart failure with preserved ejection fraction in
patients with an exacerbation of chronic obstructive pulmonary disease.
AB - Diagnosing heart failure with preserved ejection fraction (HFpEF) in patients
with chronic obstructive pulmonary disease (COPD) is difficult due to overlapping
pathophysiological pathways, risk factors and clinical presentations. We
investigated the prevalence and prognostic implications of coexisting HFpEF in
patients hospitalized for acute exacerbation of COPD. A total of 116 consecutive
patients with an acute exacerbation of COPD were evaluated for HFpEF and followed
for an average period of 22 +/- 9 months for the occurrence of death from any
cause. HFpEF was diagnosed in 22 (19 %) patients with COPD, who were older, and
also had higher LV mass, left atrial size, and mitral E/Ea ratio than those
without HFpEF (p < 0.05 for all comparisons). HFpEF was not independently
associated with all-cause mortality [hazard ratio (HR) 1.07, 95 % confidence
interval (CI) 0.44-2.62]. Global initiative for chronic Obstructive Lung Disease
(GOLD) stage (IV vs. I-III, HR 2.37, CI 1.23-4.59) and N-terminal pro B-type
natriuretic peptide (NT-proBNP) levels (HR 2.79, CI 1.12-6.98) were independent
predictors of long-term survival. HFpEF is present in one-fifth of patients with
exacerbated COPD. Non-invasively diagnosed HFpEF may not be an independent
predictor of all-cause mortality. Elevated NT-proBNP levels and very severe COPD
were independently associated with unfavorable overall survival.
PMID- 26423074
TI - Ex-Situ Remediation Technologies for Environmental Pollutants: A Critical
Perspective.
AB - Pollution and the global health impacts from toxic environmental pollutants are
presently of great concern. At present, more than 100 million people are at risk
from exposure to a plethora of toxic organic and inorganic pollutants. This
review is an exploration of the ex-situ technologies for cleaning-up the
contaminated soil, groundwater and air emissions, highlighting their principles,
advantages, deficiencies and the knowledge gaps. Challenges and strategies for
removing different types of contaminants, mainly heavy metals and priority
organic pollutants, are also described.
PMID- 26423075
TI - Lead Exposure and Oxidative Stress: A Systematic Review.
AB - Lead is an environmental toxicant that can induce oxidative stress (OS) via
reactive oxygen species (ROS) generation, which has been reported as an important
mechanism underlying lead toxicity (Gurer and Ercal 2000; Pande and Flora 2002;
Kasperczyk et al. 2004a; Farmand et al. 2005; Verstraeten et al. 2008; Wang et
al. 2009; Martinez-Haro et al. 2011). OS occurs when the generation of ROS
exceeds the antioxidant system's ability to defend cells against oxidized
molecules. ROS is a term generally used to refer to free radicals derived from O2
(e.g., superoxide anions [O2-] and hydroxyl radicals [OH-]) or to non-radical
species (e.g. hydrogen peroxide [H2O2]) (Halliwell and Cross 1994).
PMID- 26423076
TI - Nanostructured Metal Oxides for Stoichiometric Degradation of Chemical Warfare
Agents.
AB - Metal oxides have very important applications in many areas of chemistry, physics
and materials science; their properties are dependent on the method of
preparation, the morphology and texture. Nanostructured metal oxides can exhibit
unique characteristics unlike those of the bulk form depending on their
morphology, with a high density of edges, corners and defect surfaces. In recent
years, methods have been developed for the preparation of metal oxide powders
with tunable control of the primary particle size as well as of a secondary
particle size: the size of agglomerates of crystallites. One of the many ways to
take advantage of unique properties of nanostructured oxide materials is
stoichiometric degradation of chemical warfare agents (CWAs) and volatile organic
compounds (VOC) pollutants on their surfaces.
PMID- 26423077
TI - Ecological Recovery Potential of Freshwater Organisms: Consequences for
Environmental Risk Assessment of Chemicals.
AB - Chemical contaminants released into the in the environment may have adverse
effects on (non-target) species, populations and communities. The return of a
stressed system to its pre-disturbance or other reference state, i.e. the
ecological recovery, may depend on various factors related to the affected taxon,
the ecosystem of concern and the type of stressor with consequences for the
assessment and management of risks associated with chemical contaminants. Whereas
the effects caused by short-term exposure might be acceptable to some extent, the
conditions under which ecological recovery can serve as a decision criterion in
the environmental risk assessment of chemical stressors remains to be evaluated.
For a generic consideration of recovery in the risk assessment of chemicals, we
reviewed case studies of natural and artificial aquatic systems and evaluate five
aspects that might cause variability in population recovery time: (1) taxonomic
differences and life-history variability, (2) factors related to ecosystem type
and community processes, (3) type of disturbance, (4) comparison of field and
semi-field studies, and (5) effect magnitude, i.e., the decline in population
size following disturbance. We discuss our findings with regard to both
retrospective assessments and prospective risk assessment.
PMID- 26423078
TI - Soluble Dietary Fibers Can Protect the Small Intestinal Mucosa Without Affecting
the Anti-inflammatory Effect of Indomethacin in Adjuvant-Induced Arthritis Rats.
AB - BACKGROUND/AIM: How to prevent the small intestinal damage induced by NSAIDs is
an urgent issue to be resolved. In the present study, we examined the effects of
soluble dietary fibers on both anti-inflammatory and ulcerogenic effects of
indomethacin in arthritic rats. METHODS: Male Wistar rats weighing 180-220 g were
used. Arthritis was induced by injecting Freund's complete adjuvant (killed M.
tuberculosis) into the plantar region of the right hindpaw. The animals were fed
a regular powder diet for rats or a diet supplemented with soluble dietary fibers
such as pectin or guar gum. Indomethacin was administered once a day for 3 days
starting 14 days after the adjuvant injection, when marked arthritis was
observed. The volumes of the hindpaw were measured before and after indomethacin
treatment to evaluate the effect of indomethacin on edema. The lesions in the
small intestine were examined 24 h after the final dosing of indomethacin.
RESULTS: Hindpaw volume was increased about 3 times 14 days after injection of
the adjuvant. Indomethacin (3-10 mg/kg, p.o.) decreased hindpaw volume dose
dependently, but caused severe lesions in the small intestine at doses of 6 and
10 mg/kg. The addition of pectin (1-10 %) or guar gum (10 %) to the diet markedly
decreased the lesion formation without affecting the anti-edema action of
indomethacin. The same effects of pectin were observed when indomethacin was
administered subcutaneously. CONCLUSIONS: It is suggested that soluble dietary
fibers can prevent intestinal damage induced by NSAIDs without affecting the anti
inflammatory effect of these agents.
PMID- 26423079
TI - Diagnostic Utility of Endoscopic Retrograde Cholangiography/Intraductal
Ultrasound (ERC/IDUS) in Distinguishing Malignant from Benign Bile Duct
Obstruction.
AB - BACKGROUND AND AIM: Accurately differentiating malignant diseases from benign
ones in patients having bile duct obstruction is of significant importance and
remains a major clinical problem. This study investigated the diagnostic yield of
endoscopic retrograde cholangiography/intraductal ultrasound (ERC/IDUS) in
distinguishing malignant from benign bile duct obstruction and assessed some
image findings from ERC/IDUS which might be useful in differentiation. METHODS:
From January 2008 to January 2015, patients who underwent ERC/IDUS for bile duct
obstruction were enrolled. Patient's ERC/IDUS diagnosis was compared with the
final diagnosis determined by pathologic findings and/or clinical outcome of
follow-up. RESULTS: One hundred and ninety-three patients with bile duct
obstruction were included. IDUS correctly identified 94 of 97 malignant diseases
and 76 of 96 benign diseases with sensitivity, specificity, and accuracy rate of
96.91, 79.17, and 88.08 %, respectively. Additionally, the accuracy rate of IDUS
for diagnosis of proximal bile duct obstruction was higher than that of distal
bile duct obstruction (98.08 vs. 82.73 %, p = 0.006). Besides, there was a
significant difference in the length at the obstruction site between benign and
malignant diseases (13.76 +/- 7.37 vs. 19.97 +/- 11.37 mm, p < 0.001) as well as
thickness of bile duct wall at the site of obstruction (3.06 +/- 0.92 vs. 7.03 +/
3.70 mm, p = 0.008). Biliary wall thickness >7 mm without extrinsic compression
had a positive predictive value (PPV) of 100 % for including malignancy, while
length ?20 mm demonstrated a PPV of 93.44 %. CONCLUSIONS: ERC/IDUS is effective
in distinguishing malignant from benign bile duct obstruction, thus helping in
further clinical management.
PMID- 26423080
TI - Analysis of Hospital-Based Emergency Department Visits for Inflammatory Bowel
Disease in the USA.
AB - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, debilitating condition
with high emergency department (ED) utilization. We aimed to investigate the
utilization patterns of ED by IBD patients and measure hospitalization and
surgical rates following ED visits. METHODS: We conducted a cross-sectional study
of adults with IBD listed as the primary ED diagnosis from the 2009 to 2011
Nationwide Emergency Department Sample. The characteristics of the IBD-related ED
visits in relation to following hospitalizations and surgeries were analyzed.
RESULTS: Adult IBD patients constitute 0.09 % of the total ED visits. Crohn's
disease (CD) contributed to 69 % of the IBD-ED visits. The hospitalization rate
from ED was 59.9 % nationally, ranging from 56 % in west to 69 % in northeast.
The most significant factors associated with hospitalization were intra-abdominal
abscess [odds ratio (OR) 24.22], bowel obstruction (OR 17.77), anemia (OR 7.54),
malnutrition (OR 6.29), hypovolemia/electrolyte abnormalities (OR 5.57), and
fever/abnormal white cell count (OR 3.18). Patients with CD (OR 0.66), low-income
group (OR 0.90), and female gender (OR 0.87) have a lower odds of getting
hospitalized. Age above 65 years (OR 1.63), CD (OR 1.89), bowel obstruction (OR
9.24), and intra-abdominal abscess (OR 18.41) were significantly associated with
surgical intervention. CONCLUSION: The IBD-related ED visits have remained
relatively stable from 2009 to 2011. The presence of anemia, malnutrition,
hypovolemia, electrolyte abnormalities, fever, abnormal white cell count, bowel
obstruction, or intra-abdominal abscess during the ED visit was associated with
hospitalization. The presence of bowel obstruction and intra-abdominal abscess
was strongly associated with surgical intervention.
PMID- 26423081
TI - Morphological Characteristics of Early Gastric Neoplasms Detected After
Helicobacter pylori Eradication.
AB - BACKGROUND: Previous morphological studies indicated that the eradication of
Helicobacter pylori (H. pylori) made gastric neoplasms endoscopically indistinct
through the flattening and covering of tumors with a non-neoplastic epithelium
(NE). AIM: To validate these alterations. METHODS: We reviewed and compared the
endoscopic and histological findings of early gastric carcinomas and high-grade
dysplasias resected endoscopically from H. pylori-infected and H. pylori
eradicated patients. The extent of NE covering a tumor was expressed as the
histological length ratio of NE to the tumor. Tumor morphology was compared
before and after therapies in patients who received H. pylori eradication
treatments during the period from tumor discovery to endoscopic resection.
RESULTS: NE-covered ratios were higher in the 59 tumors detected after the
eradication of H. pylori than in the 152 tumors detected during the infection
(median 8 vs. 0 %, respectively), whereas the frequency at which an elevated
morphology and whitish discoloration of a tumor were observed was less (14 vs. 56
%, and 14 vs. 43 %, respectively). These were also independent characteristics
for tumors detected after the eradication of H. pylori. Two elevated tumors
showing whitish discoloration out of 16 tumors became endoscopically indistinct
following H. pylori eradication treatments through the flattening of tumors and
muting of the discoloration. CONCLUSION: The eradication of H. pylori promoted
covering with NE, the flattening of tumors, and muting of the whitish
discoloration, which may make a subset of tumors, potentially including whitish
elevated neoplasms, indistinct.
PMID- 26423082
TI - Enteractinococcus lamae sp. nov. and Enteractinococcus viverrae sp. nov.,
isolated from animal faeces.
AB - Two novel actinobacteria, designated strains YIM 101617(T) and YIM 101632(T),
were isolated from Lama pacos (alpaca) and Viverra zibetha (civet) faeces in
Yunnan Wild Animal Park in Yunnan province, southwestern China. Both strains
should be placed in genus Enteractinococcus based on phylogenetic analysis. Based
on 16S rRNA gene sequence analysis, strain YIM 101617(T) exhibits high similarity
to Enteractinococcus fodinae DSM 22966(T) (97.70 %) and Enteractinococcus
coprophilus YIM 100590(T) (97.45 %), whilst YIM 101632(T) exhibits high
similarity to Enteractinococcus coprophilus YIM 100590(T) (97.25 %), and the
similarity between YIM 101617(T) and YIM 101632(T) is 95.90 %. However, DNA-DNA
hybridization values of the two strains with the type strains in the genus
Enteractinococcus were low (<70 %). Most morphological and chemotaxonomic
characteristics of the two strains were found to be similar to those of species
in the genus Enteractinococcus but also some differences were observed. The DNA
G+C contents of strains YIM 101617(T) and YIM 101632(T) were determined to be
55.9 and 56.4 mol%, respectively. Based on these data, the two strains are
concluded to represent two different novel species in the genus
Enteractinococcus. The names Enteractinococcus lamae sp. nov. (type strain YIM
101617(T)=DSM 27612(T)=CCTCC AB 2013230(T)) and Enteractinococcus viverrae sp.
nov. (type strain YIM 101632(T)=KCTC 39552(T)=CCTCC AB 2013280(T)) are proposed,
respectively.
PMID- 26423083
TI - Treatment of Cardiovascular Risk Factors in Women.
AB - Cardiovascular disease (CVD) is a leading cause of death for both women and men.
Common traditional risk factors for CVD, such as hypercholesterolemia,
hypertension and smoking have a high prevalence in women and in some cases a
greater health impact compared with men. Nevertheless, risk factors are treated
less often and less aggressively in women than in men, partly due to decreased
awareness on the part of public health opinion makers, patients and physicians.
About seventy five percent of all coronary heart disease deaths among women could
be avoided if CVD risk factors like hypercholesterolemia, hypertension and
smoking are adequately treated. This narrative review discusses the treatment of
the 4 CVD risk factors, namely hypercholesterolemia, hypertension, smoking and
diabetes. These risk factors were examined in the Framingham Heart study and
years later they were found in the INTERHEART study to be the 4 most important
risk factors for the development of CVD.
PMID- 26423084
TI - Unique Coronary Artery Disease Differences in Women as Related to
Revascularization.
AB - There are significant differences in coronary heart disease (CHD) in women
whenever a comparison is made to men and these carry over to revascularization
procedures including percutaneous coronary intervention (PCI) and coronary artery
bypass graft (CABG) surgery. The coronary arteries of women are smaller, which
presents additional challenges for PCI and CABG procedures. Unique atypical
symptomatology in response to acute coronary syndrome (ACS) in women can confound
diagnosis, women notoriously delay seeking medical help for ACS, and physicians
and other caregivers have had a tendency to minimize the significance of these
symptoms, contributing further to a delay in necessary care. There also appears
to be an increased association of inflammation and CHD in women. The younger the
female patient with CHD, the higher the mortality and that mortality clearly
exceeds that of comparable male patients. For cardiovascular (CV) risk prevention
in women, statins have had controversy associated with their use but overall, the
proof of beneficial outcomes results from statins is also valid in women. An
increased rate of adverse outcomes has been reported in women after PCI and CABG
surgery. These worse clinical outcomes have persisted in contemporary years but
lessened due to advancement in invasive techniques. Nevertheless, PCI that could
improve clinical outcomes in women who have high-risk ACS is, unfortunately,
performed on a less frequent basis and, in addition, there are greater delays
involving women as compared to men. With increased clinical comorbidity
associated with complex CHD in women, a lower anatomical SYNTAX score (from:
SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery
[SYNTAX] trial) appears necessary in order for women to achieve a similar long
term mortality benefit from CABG surgery as compared to PCI.
PMID- 26423085
TI - On the evolutionary advantage of coagulation factor V Leiden (FVL).
AB - Carriership of coagulation factor V Leiden (FVL) is by far the most common
thrombophilia in Western populations. FVL is caused by a single point mutation in
the gene coding for coagulation factor V (FV) causing a lifelong procoagulatory
state with an increased risk of venous thromboembolism (VTE) which might be
fatal. It is believed that the mutation occurred in one person 21,000 years ago
and today 3% to 15% of the Western populations are carriers. A potentially
dangerous mutation such as FVL ought to be rare and should have been reduced, if
not eradicated, by selection during the course of human evolution. Thus, FVL must
confer the carriers with an evolutionary advantage in order to be so prevalent.
Lower risk of profuse bleeding and increased fecundity might give carriers an
advantage. In this paper we give an updated short background and discuss possible
evolutionary advantages and disadvantages.
PMID- 26423086
TI - Non-viral Delivery Systems for the Application in p53 Cancer Gene Therapy.
AB - A key barrier to the development of gene therapy remains the lack of safe,
efficient and easily controllable vehicles for gene delivery. The fundamental
problems associated with the viral vehicles, e.g. lack of specificity and
immunogenic potential, have driven the development of non-viral systems of gene
delivery. In the last decade, studies on p53 gene replacement therapy have
dominated the literature. Although clinical trials of p53 gene therapy have
achieved limited success, it remains the only tumor suppressor gene to be
evaluated formally in clinical trials for cancer treatment, with increasing focus
on delivery using non-viral systems. In this article, we particularly review
current investigations on p53 gene delivery using non-viral methods, including
both physical and chemical approaches, with an emphasis on the latter. The
existing opportunities and challenges for successful p53 cancer gene therapy are
also discussed.
PMID- 26423087
TI - Silver and other metals in the treatment of gastrointestinal diseases.
AB - Disturbance in the functioning of the gastrointestinal (GI) tract can critically
affect the health and even the life of the whole organism. Several factors, both
exo- and endogenous may contribute to the dysregulation of homeostasis in the
digestive system, including genetic background, ingestion of highly processed
food, exposition to environmental pollution or chronic stress, and changes in gut
microflora, to name just a few. An important number of these factors rely on
metals, which often play a dual, stimulatory and inhibitory role in crucial
physiological processes. In this paper, we focus on the structures incorporating
silver, copper and other metals as future drugs against GI diseases. We
critically review available literature for their effectiveness and potential
application, and discuss clinical relevance of these findings.
PMID- 26423088
TI - Calcium-related neurotoxicity of oxaliplatin: understanding the mechanisms to
drive therapy.
AB - Oxaliplatin is one of the most widely used anticancer drugs representing the
cornerstone of the treatment of colorectal cancer. Yet a number of side effects,
including oxaliplatin- induced peripheral neurotoxicity (OIPN) which represents a
dose-limiting side effect in the clinical use of oxaliplatin, limit its use and a
better understanding of its pathogenesis would offer a great opportunity to
improve the "quality of survival" of cancer patients. So far, no treatment able
to prevent or limit OIPN has been approved, and one of the reasons for this unmet
clinical need is the incomplete knowledge of its pathogenesis preventing the
development of rationalebased pharmacological interventions. Preclinical and
clinical evidence raised the hypothesis that intracellular calcium-related events
might play an important role in the onset of OIPN. Yet, the results of
mechanistic pre-clinical studies appear inconsistent and, therefore, their
relevance in neuroprotective drugs design is still uncertain. Indeed, it is at
present unclear whether aberrant calcium signalling is the key pathogenetic
moment or whether it just constitutes the mediator of the clinical phenotype.
This review will summarize the preclinical results involving calcium-related
events and OIPN with the aim to provide an updated overview of the available
evidence and highlight the most promising strategies to design effective
neuroprotective drugs. In particular, we will focus on the pre-clinical evidence
suggesting that TRPV1, TRPM8 or TRPA1 might be involved, as these appear
particularly amenable to pharmacological modulation.
PMID- 26423089
TI - Authors' reply to Gupta.
PMID- 26423090
TI - Middle East respiratory syndrome coronavirus (MERS-CoV) in pilgrims returning
from the Hajj.
PMID- 26423091
TI - Elastofibroma With Amyloid Deposition.
PMID- 26423092
TI - End-of-life care in patients with primary malignant brain tumors: early is
better.
PMID- 26423093
TI - Hue Selectivity in Human Visual Cortex Revealed by Functional Magnetic Resonance
Imaging.
AB - The variability of color-selective neurons in human visual cortex is considered
more diverse than cone-opponent mechanisms. We addressed this issue by deriving
histograms of hue-selective voxels measured using fMRI with a novel stimulation
paradigm, where the stimulus hue changed continuously. Despite the large between
subject difference in hue-selective histograms, individual voxels exhibited
selectivity for intermediate hues, such as purple, cyan, and orange, in addition
to those along cone-opponent axes. In order to rule the possibility out that the
selectivity for intermediate hues emerged through spatial summation of activities
of neurons selectively responding to cone-opponent signals, we further tested hue
selective adaptations in intermediate directions of cone-opponent axes, by
measuring responses to 4 diagonal hues during concurrent adaptation to 1 of the 4
hues. The selective and unidirectional reduction in response to the adapted hue
lends supports to our argument that cortical neurons respond selectively to
intermediate hues.
PMID- 26423094
TI - Hepatic lipase deficiency produces glucose intolerance, inflammation and hepatic
steatosis.
AB - Metabolic syndrome and type 2 diabetes mellitus constitute a major problem to
global health, and their incidence is increasing at an alarming rate. Non
alcoholic fatty liver disease, which affects up to 90% of obese people and nearly
70% of the overweight, is commonly associated with MetS characteristics such as
obesity, insulin resistance, hypertension and dyslipidemia. In the present study,
we demonstrate that hepatic lipase (HL)-inactivation in mice fed with a high-fat,
high-cholesterol diet produced dyslipidemia including hypercholesterolemia,
hypertriglyceridemia and increased non-esterified fatty acid levels. These
changes were accompanied by glucose intolerance, pancreatic and hepatic
inflammation and steatosis. In addition, compared with WT mice, HL(-/-) mice
exhibited enhanced circulating MCP1 levels, monocytosis and higher percentage of
CD4+Th17+ cells. Consistent with increased inflammation, livers from HL(-/-) mice
had augmented activation of the stress SAPK/JNK- and p38-pathways compared with
the activation levels of the kinases in livers from WT mice. Analysis of HL(-/-)
and WT mice fed regular chow diet showed dyslipidemia and glucose intolerance in
HL(-/-) mice without any other changes in inflammation or hepatic steatosis.
Altogether, these results indicate that dyslipidemia induced by HL-deficiency in
combination with a high-fat, high-cholesterol diet promotes hepatic steatosis and
inflammation in mice which are, at least in part, mediated by the activation of
the stress SAPK/JNK- and p38-pathways. Future studies are warranted to asses the
viability of therapeutic strategies based on the modulation of these kinases to
reduce hepatic steatosis associated to lipase dysfunction.
PMID- 26423095
TI - Recombinant human thyrotropin preparation for adjuvant radioiodine treatment in
children and adolescents with differentiated thyroid cancer.
AB - AIM: Although recombinant human thyrotropin (rhTSH) is widely used in treating
differentiated thyroid cancer (DTC), almost all clinical investigation has been
in adults. The aim of our retrospective study was to evaluate outcomes of
adjuvant, rhTSH-aided radioiodine treatment in children/adolescents with DTC and
to compare them to (131)I therapy during l-thyroxin withdrawal (THW). METHODS:
Patients with the diagnosis of DTC who were <=18 years of age and had no signs of
persistent disease at the time of (131)I treatment were included; 48 patients
were treated after rhTSH (rhTSH group) and 82 after THW group. The median time of
follow-up after therapy was 67 months and was longer in the THW group (99 vs 43
months, P<0.05). RESULTS: On the day of (131)I administration, all but one
patient had TSH levels above 25 MUIU/ml. Peak TSH concentration was significantly
higher in the rhTSH group (152 MUIU/ml vs 91 MUIU/ml). Similarly, the
thyroglobulin concentration was higher in the rhTSH group (9.7 ng/ml vs 1.8
ng/ml). No side effects requiring medical intervention were recorded after rhTSH
administration. The evaluation of disease outcomes during TSH stimulation (6-18
months after (131)I treatment) revealed equal rates of thyroid ablation (71%) in
both groups. During subsequent follow-up, five patients showed recurrence
(P>0.05). CONCLUSIONS: In children/adolescents, rhTSH-aided adjuvant radioiodine
treatment is associated with rates of remnant ablation and short-term recurrence
similar to THW. As this preparation has several advantages over THW, rhTSH may
become the preferred method of TSH stimulation once studies of long-term outcomes
show non-inferiority to THW in this age group.
PMID- 26423096
TI - Evaluation of a culturally adapted training course in Indigenous e-mental health.
AB - OBJECTIVE: To report the impact of the Indigenous e-mental health training course
'Yarning about Indigenous Mental Health using the AIMhi Stay Strong App'. METHOD:
Participants were trained in e-mental health and the use of one of the first
culturally adapted e-mental health interventions - The AIMhi Stay Strong App.
Between October 2013 and December 2014, 138 participants completed the 'Yarning
about Indigenous Mental Health using the AIMhi Stay Strong App' training course
and 130 completed pre- and post-training questionnaires to explore knowledge and
confidence in a number of areas trained. RESULTS: Paired t-tests showed
significant improvements across all measures of skill and knowledge except for
confidence in using computers. CONCLUSIONS: E-mental health is a relatively new
development that may contribute to improved access to mental health services for
rural and remote Indigenous Australians, particularly where such tools are
culturally adapted. Whilst current knowledge and use of e-mental health tools in
this group of Northern Territory service providers was limited, perceived
knowledge and confidence in use was significantly improved following training.
PMID- 26423097
TI - Prevalence and Diagnosis Rates of Childhood ADHD Among Racial-Ethnic Groups in a
Public Mental Health System.
AB - OBJECTIVE: This study estimated the proportions of Hispanic and non-Hispanic
white and black children ages three to 17 with a diagnosis of attention-deficit
hyperactivity disorder (ADHD) receiving services from the New York State public
mental health system (NYS PMHS) and their annual treated ADHD prevalence rates.
Findings were compared with those of recent national studies of general
population samples. METHODS: Data were from a 2011 survey of users of NYS PMHS
nonresidential services. Adjusted odds ratios compared the probability of an ADHD
diagnosis among the groups by age, gender, and insurance type. Prevalence rates
were compared among groups by age and gender. RESULTS: An estimated 133,091
children used the NYS PMHS, of whom 31% had an ADHD diagnosis. The prevalence
rate of ADHD among whites was significantly lower than that among Hispanics or
blacks in all gender and age groups except Hispanic females ages 13 to 17. White
children were significantly less likely than black children to receive an ADHD
diagnosis. CONCLUSIONS: National studies have reported higher ADHD rates among
white children. Compared with children in the NYS PMHS, those in national studies
had multiple access points to care, including private psychiatrists and
clinicians and primary care practitioners. The higher reported ADHD rates in
national studies may reflect higher rates of private insurance among white
children, which would increase the likelihood of their using private
practitioners. Cultural factors that influence whether and where care is sought
and whether practitioners appropriately diagnosis ADHD may also explain the
difference in findings.
PMID- 26423098
TI - Practices of Depression Care in Home Health Care: Home Health Clinician
Perspectives.
AB - OBJECTIVE: The study assessed gaps between published best practices and real
world practices of treating depression in home health care (HHC) and barriers to
closing gaps. METHODS: The qualitative study used semistructured interviews with
nurses and administrators (N=20) from five HHC agencies in five states. Audio
recorded interviews were transcribed and analyzed by a multidisciplinary team
using grounded theory method to identify themes. RESULTS: Routine HHC nursing
overlapped with all functional areas of depression care. However, gaps were noted
between best and real-world practices. Gaps were associated with perceived scope
of practice by HHC nurses, knowledge gaps and low self-efficacy in depression
treatment, stigma attached to depression, poor quality of antidepressant
management in primary care, and poor communication between HHC and primary care
clinicians. CONCLUSIONS: Strategies to close gaps between typical and best
practices include enhancing HHC clinicians' knowledge and self-efficacy with
depression treatment and improving the quality of antidepressant management and
communication with primary care.
PMID- 26423099
TI - Provider and Nonprovider Sources of Mental Health Help in the Military and the
Effects of Stigma, Negative Attitudes, and Organizational Barriers to Care.
AB - OBJECTIVE: This study examined sources of help (providers or nonproviders) used
by soldiers for mental health problems. Differences in perceived barriers to care
by type of help used were also assessed. METHODS: Active-duty soldiers from four
brigade combat teams (N=3,380) were surveyed in 2008-2009. Items assessed
posttraumatic stress disorder; depression; anxiety; help needed because of a
stress, emotional, alcohol, or family problem; stigma; negative attitudes toward
care; and organizational barriers. Participants reported receipt of help in the
past three months from providers (mental health or medical professionals or an
Army resource hotline) or nonproviders (fellow soldier, medic, chaplain, or chain
of command). RESULTS: Nearly a third (31%) were identified as being in need of
mental health care. Of those, 5% reported using nonprovider help exclusively, 14%
used provider help exclusively, and 7% used both types. Stigma was rated
significantly lower as a barrier among those who used help exclusively from
providers than among those who did not use help from any source; however, no
significant differences in stigma scores were found between those who used help
from nonproviders and those who did not use help from any source. Soldiers who
used help from nonproviders were more likely than those who used help from
providers to perceive organizational barriers. CONCLUSIONS: Results show that
soldiers may view nonproviders as alternative sources of mental health help,
suggesting that the Army should ensure that such resources are adequately trained
and integrated into the mental health community so that soldiers can receive the
help they need.
PMID- 26423100
TI - Use of Active-Play Video Games to Enhance Aerobic Fitness in Schizophrenia:
Feasibility, Safety, and Adherence.
AB - OBJECTIVE: Active-play video games have been used to enhance aerobic fitness in
various clinical populations, but their use among individuals with schizophrenia
has been limited. METHODS: Feasibility, acceptability, safety, and adherence data
were obtained for use of aerobic exercise (AE) equipment by 16 individuals with
schizophrenia during a 12-week AE program consisting of three one-hour exercise
sessions per week. Equipment included exercise video games for Xbox 360 with
Kinect motion sensing devices and traditional exercise equipment. RESULTS: Most
participants (81%) completed the training, attending an average of 79% of
sessions. The proportion of time spent playing Xbox (39%) exceeded time spent on
any other type of equipment. When using Xbox, participants played 2.24+/-1.59
games per session and reported high acceptability and enjoyment ratings, with no
adverse events. CONCLUSIONS: Measures of feasibility, acceptability, adherence,
and safety support the integration of active-play video games into AE training
for people with schizophrenia.
PMID- 26423101
TI - Perception of Coercion Among Patients With a Psychiatric Community Treatment
Order: A Literature Review.
AB - OBJECTIVE: Various forms of compulsory psychiatric community treatment orders
(CTOs) are commonly utilized internationally. CTOs remain contentious because of
the ethical implications of coercing patients to receive treatment. Understanding
patients' experience of CTOs can assist in the development of more patient
centered and recovery-focused community care. This review examined the
relationship between CTOs and patients' perceptions of coercion in the
literature. METHODS: A search of key terms relating to CTOs and patients'
perceptions of coercion was conducted of relevant databases from their inception
to March 31, 2014. Publications were included if they were peer reviewed,
reported on original research, surveyed or interviewed patients who were or had
been subject to a CTO, and were written in English. Factors influencing patients'
perceptions of coercion, including the regional context of the studies, were
identified. RESULTS: Twenty-three primary research articles, reporting on 14
studies from seven countries, were included. Evidence indicated that CTOs may
contribute to a patient's sense of coercion, with marked variations among studies
in the levels of coercion. Contextual factors, including perceptions of
alternatives to CTOs, the presence of additional forms of leverage in patients'
lives, and the process of CTO initiation and enforcement, may mitigate or enhance
perceptions of coercion. CONCLUSIONS: Coercive elements of CTOs may be reduced
through increased patient access to information, better working relationships
with service providers, and accessible, fair processes. The coercive aspects of
CTOs should be seen as part of a broader understanding of the daily pressures and
leverage applied in outpatient psychiatric treatment.
PMID- 26423102
TI - The Impact of Psychiatric Practice Guidelines on Medication Costs and Youth
Aggression in a Juvenile Justice Residential Treatment Program.
AB - OBJECTIVE: Stakeholders have expressed concern over the appropriate use of
psychiatric medications and adequacy of mental health services for youths
involved with the juvenile justice system. This study assessed the impact of
implementing psychiatric practice guidelines on medication costs and youth
aggression in a juvenile justice facility. The study examined whether
implementing psychiatric practice guidelines in a facility with an organized
psychosocial treatment program would reduce psychiatric medication costs,
compared with two other facilities, and whether lower psychotropic medication
costs would be associated with increases in youth aggression. METHODS:
Administrative data from three state-run juvenile justice facilities were
analyzed to determine psychiatric medication costs and rates of youth aggression.
Psychiatric practice guidelines that involved screening, shared decision making,
psychosocial treatments, medication prescribing, and monitoring of side effects
were implemented in only one of the three facilities, with a goal of applying
evidence-based psychopharmacology and benefit-risk considerations. RESULTS: Over
the ten-year study period (2003-2012), psychiatric medication costs decreased 26%
at the facility implementing the psychiatric practice guidelines, whereas costs
at the two comparison facilities increased by 104% and 152%. As psychiatric
medication costs decreased at the facility implementing the guidelines, youth
aggression there did not increase. CONCLUSIONS: Implementing psychiatric practice
guidelines in juvenile justice facilities can reduce psychotropic medication
costs without an increase in youth aggression. Implementation of the guidelines
requires an organized psychosocial treatment program to help deter an
inappropriate focus on psychotropic treatments.
PMID- 26423103
TI - Same-Day Integrated Mental Health Care and PTSD Diagnosis and Treatment Among VHA
Primary Care Patients With Positive PTSD Screens.
AB - OBJECTIVE: The study examined whether same-day integrated mental health services
are associated with increased diagnosis and treatment initiation among primary
care patients with positive posttraumatic stress disorder (PTSD) screens.
METHODS: Data were from a national sample of Veterans Health Administration (VHA)
primary care patients with a positive PTSD screen (N=21,427). Patients were
assessed for PTSD diagnosis and treatment initiation on the screening day and <=
7 days, <= 12 weeks, <= 6 months, and <= 1 year after screening positive. The
service setting on screening day was categorized as primary care only, same-day
primary care-mental health integration (PC-MHI), or same-day specialty mental
health care. Multivariable generalized estimating equations logistic regression
was used to estimate associations between category of screening day services and
diagnosis and treatment initiation, with adjustment for demographic
characteristics, prior psychiatric diagnoses, prior VHA service utilization, and
PTSD screen score. RESULTS: Of the 21,427 patients with positive PTSD screens,
10,809 (50.4%) received a diagnosis within one year of screening positive. Same
day PC-MHI services were associated with greater odds of PTSD diagnosis, both on
the same day as (odds ratio [OR]=2.23) and one year (OR=1.67) after screening
positive compared with primary care-only services (p<.001). Among those who
received a diagnosis on the same day as their positive screen, same-day PC-MHI
services were associated with increased odds of initiating PTSD treatment
(OR=3.39) within 12 weeks of diagnosis, compared with primary care only (p<.001).
CONCLUSIONS: Same-day integrated mental health services may help facilitate PTSD
diagnosis and treatment initiation after a positive screen.
PMID- 26423105
TI - XXI Congress of the Italian Society of Neonatology.
PMID- 26423104
TI - Homeless Veterans Eligible for Medicaid Under the Affordable Care Act.
AB - OBJECTIVE: Among homeless veterans and those at risk of homelessness currently
enrolled in Veterans Affairs (VA) health care, this study examined the proportion
likely to become eligible for Medicaid in 2014 and their health needs. METHODS: A
total of 114,497 homeless and at-risk veterans were categorized into three
groups: currently covered by Medicaid, likely to become eligible for Medicaid,
and not likely. RESULTS: Seventy-eight percent of the sample was determined to be
likely to become eligible for Medicaid in states that expand Medicaid. Compared
with veterans not likely to become eligible for Medicaid, those likely to become
eligible were less likely to have general medical and psychiatric conditions and
to have a VA service-connected disability but more likely to have substance use
disorders. CONCLUSIONS: Programs serving homeless and at-risk veterans should
anticipate the potential interplay between VA health care and the expansion of
Medicaid in states that implement the expansion.
PMID- 26423106
TI - Application of real-time machine learning to myoelectric prosthesis control: A
case series in adaptive switching.
AB - BACKGROUND: Myoelectric prostheses currently used by amputees can be difficult to
control. Machine learning, and in particular learned predictions about user
intent, could help to reduce the time and cognitive load required by amputees
while operating their prosthetic device. OBJECTIVES: The goal of this study was
to compare two switching-based methods of controlling a myoelectric arm: non
adaptive (or conventional) control and adaptive control (involving real-time
prediction learning). STUDY DESIGN: Case series study. METHODS: We compared non
adaptive and adaptive control in two different experiments. In the first, one
amputee and one non-amputee subject controlled a robotic arm to perform a simple
task; in the second, three able-bodied subjects controlled a robotic arm to
perform a more complex task. For both tasks, we calculated the mean time and
total number of switches between robotic arm functions over three trials.
RESULTS: Adaptive control significantly decreased the number of switches and
total switching time for both tasks compared with the conventional control
method. CONCLUSION: Real-time prediction learning was successfully used to
improve the control interface of a myoelectric robotic arm during uninterrupted
use by an amputee subject and able-bodied subjects. CLINICAL RELEVANCE: Adaptive
control using real-time prediction learning has the potential to help decrease
both the time and the cognitive load required by amputees in real-world
functional situations when using myoelectric prostheses.
PMID- 26423107
TI - Axial bone-socket displacement for persons with a traumatic transtibial
amputation: The effect of elevated vacuum suspension at progressive body-weight
loads.
AB - BACKGROUND: Elevated vacuum suspension systems use a pump to draw air from the
socket with the intent of reducing bone-socket motion as compared to passive
suction systems. However, it remains unknown if elevated vacuum suspension
systems decrease limb displacement uniformly during transitions from unloaded to
full-body-weight support. OBJECTIVES: To compare limb-socket motion between
elevated vacuum and passive suction suspension sockets using a controlled loading
paradigm. STUDY DESIGN: Comparative analysis. METHODS: Persons with transtibial
amputation were assessed while wearing either an elevated vacuum or passive
suction suspension socket. Digital video fluoroscopy was used to measure axial
bone-socket motion while the limb was loaded in 20% body-weight increments. An
analysis of variance model was used to compare between suspension types. RESULTS:
Total axial displacement (0%-100% body weight) was significantly lower using the
elevated vacuum (vacuum: 1.3 cm, passive suction: 1.8 cm; p < 0.0001). Total
displacement decreased primarily due to decreased motion during initial loading
(0%-20%; p < 0.0001). Other body-weight intervals were not significantly
different between systems. CONCLUSION: Elevated vacuum suspension reduced axial
limb-socket motion by maintaining position of the limb within the socket during
unloaded conditions. Elevated vacuum provided no meaningful improvement in limb
socket motion past initial loading. CLINICAL RELEVANCE: Excessive bone-socket
motion contributes to poor residual limb health. Our results suggest elevated
vacuum suspensions can reduce this axial displacement. Visual assessment of the
images suggests that this occurs through the reduction or elimination of the air
pocket between the liner and socket wall while the limb is unloaded.
PMID- 26423108
TI - Left Atrial Appendage Closure Reduces the Incidence of Postoperative
Cerebrovascular Accident in Patients Undergoing Cardiac Surgery.
AB - BACKGROUND: Cerebrovascular accidents (CVA) are a major adverse event following
cardiac surgery, for which atrial fibrillation (AF) is considered as a risk
factor. We have recently performed left atrial appendage (LAA) surgical closure
or amputation (LAAC/A), which is the main source of emboli, during open-heart
surgery. METHODS AND RESULTS: A prospective observational study of 1,831
consecutive patients (69.2% male, aged 66.8+/-12.2 years) undergoing cardiac
surgery between 2009 and 2013 was performed. The incidence of postoperative CVA
within 6 months in patients with and without LAAC/A was compared. We further
stratified patients according to their risk of CVA using CHA2DS2-VASc score;
dichotomizing low-risk (score <2) and high-risk groups (>=2). A total of 369
patients (20.2%) underwent LAAC/A. Although these patients had larger left atrial
diameter preoperatively and developed postoperative AF more frequently than those
without LAAC/A (45.4 vs. 41.1 mm, 49.3 vs. 39.1%, respectively, both P<0.001),
the CVA incidence was not different between the groups (3.5 vs. 3.0%, P=0.612).
Multivariate analysis revealed no association between LAAC/A and CVA in patients
with CHA2DS2-VASc score >=2, whereas in patients with CHA2DS2-VASc score <2,
LAAC/A was the only and independent factor negatively associated with CVA
development (odds ratio <10(-6); P=0.021). CONCLUSIONS: Additional LAA procedure
at the time of cardiac surgery reduces the incidence of early postoperative CVA
in patients with low CHA2DS2-VASc score.
PMID- 26423109
TI - Serum levels of ghrelin and obestatin in children with symptoms suggestive of
delayed gastric emptying of unclear etiology.
AB - BACKGROUND: Ghrelin and obestatin are peptides of the gut-brain axis affecting
appetite and gastrointestinal motility. METHODS: We conducted a cross-sectional,
case-control study to determine pre- and postprandial serum levels of total
ghrelin and obestatin along with gastric emptying scintigraphy in children with
symptoms suggestive of delayed gastric emptying time (GET), not attributable to
any identifiable cause. RESULTS: Twenty children with symptoms suggestive of
delayed GET, of whom 9 had delayed GET, and 20 age-matched healthy children were
enrolled. Preprandial ghrelin and obestatin were higher compared to controls (GHR
mean level in patients and controls: 1162 pg/mL and 401 pg/mL respectively;
P<0.05; OB mean level in patients and controls: 417 pg/mL and 325 pg/mL
respectively; not statistically significant). Postprandial ghrelin was
significantly decreased in the subgroup of patients with delayed GET (GHR mean
level in children with normal and prolonged GET: 1237 pg/mL and 584 pg/mL
respectively; P<0.05). CONCLUSION: Obestatin and ghrelin were deranged in
children with symptoms indicative of delayed GET of unexplained etiology. Gastric
emptying was prolonged in almost half of the patients thus gastric emptying
scintigraphy should be considered in the investigation of children with such
symptomatology.
PMID- 26423110
TI - Point-of-care genetic profiling and/or platelet function testing in acute
coronary syndrome.
AB - Our aim was to demonstrate that the sequential use of the Verigene(r) rapid
CYP2C19 test for genetic profiling and the VerifyNowTM bedside test for platelet
function measurement in ACS patients may optimise P2Y12 inhibition. "Rapid"
(CYP2C19*1/*1 or CYP2C19*17 carriers, n=211) and "slow" metabolisers (CYP2C19*2
carriers, n=58) were first put on clopidogrel and prasugrel for >= 2 weeks,
respectively. Patients with low platelet reactivity (PRU<30) on prasugrel or high
platelet reactivity (>208 PRU) on clopidogrel were then switched to clopidogrel
and prasugrel, respectively. Our objectives were (i) to demonstrate that the
proportion of "rapid" metabolisers on 75 mg of clopidogrel within 30-208 (PRU) of
P2Y12 inhibition is non-inferior to "slow" metabolisers on prasugrel 10 mg and
(ii) to evaluate the same end-point after switching drugs. The proportion of
"rapid" and "slow" metabolisers within 30-208 PRU of P2Y12 inhibition was 71% and
56.9%, respectively, an absolute difference of +14.1% (95% CI, -0.05% to 28.28%)
with a non-inferiority margin greater than the predefined margin of -10%. Among
patients out of target, all but one "slow" metabolisers displayed low-on
prasugrel platelet reactivity while the majority of "rapid" metabolisers (68%)
displayed high-on clopidogrel platelet reactivity. After switching, the
proportion of patients within 30-208 PRU of P2Y12 inhibition was 83.6% and 79.3%
in "rapid" and "slow" metabolisers, respectively (+4.3%, 95% CI -7.3% to 15.9%).
In conclusion, this study demonstrates a loose relationship between genotype and
platelet function phenotype approaches but that they are complementary to select
prasugrel or clopidogrel MD in stented ACS patients.
PMID- 26423111
TI - An unusual cause of odynophagia.
PMID- 26423112
TI - Prolonged suppression of HBV in mice by a novel antibody that targets a unique
epitope on hepatitis B surface antigen.
AB - OBJECTIVE: This study aimed to investigate the therapeutic potential of
monoclonal antibody (mAb) against HBV as a novel treatment approach to chronic
hepatitis B (CHB) in mouse models. METHODS: Therapeutic effects of mAbs against
various epitopes on viral surface protein were evaluated in mice mimicking
persistent HBV infection. The immunological mechanisms of mAb-mediated viral
clearance were systematically investigated. RESULTS: Among 11 tested mAbs, a
novel mAb E6F6 exhibited the most striking therapeutic effects in several HBV
persistent mice. Single-dose administration of E6F6 could profoundly suppress the
levels of hepatitis B surface antigen (HBsAg) and HBV DNA for several weeks in
HBV-transgenic mice. E6F6 regimen efficiently prevented initial HBV infection,
and reduced viral dissemination from infected hepatocytes in human-liver-chimeric
mice. E6F6-based immunotherapy facilitated the restoration of anti-HBV T-cell
response in hydrodynamic injection (HDI)-based HBV carrier mice. Immunological
analyses suggested that the Fcgamma receptor-dependent phagocytosis plays a
predominant role in E6F6-mediated viral suppression. Molecular analyses suggested
that E6F6 recognises an evolutionarily conserved epitope (GPCK(R)TCT) and only
forms a smaller antibody-viral particle immune complex with limited interparticle
crosslinking when it binds to viral particles. This unique binding characteristic
of E6F6 to HBV was possibly associated with its effective in vivo
opsonophagocytosis for viral clearance. CONCLUSIONS: These results provided new
insight into understanding the therapeutic role and mechanism of antibody against
persistent viral infection. The E6F6-like mAbs may provide a novel
immunotherapeutic agent against human chronic HBV infection.
PMID- 26423113
TI - Specific members of the predominant gut microbiota predict pouchitis following
colectomy and IPAA in UC.
AB - OBJECTIVE: Pouchitis is the most common complication after colectomy with ileal
pouch-anal anastomosis (IPAA) for UC and the risk is the highest within the 1st
year after surgery. The pathogenesis is not completely understood but clinical
response to antibiotics suggests a role for gut microbiota. We hypothesised that
the risk for pouchitis can be predicted based on the faecal microbial composition
before colectomy. DESIGN: Faecal samples from 21 patients with UC undergoing IPAA
were prospectively collected before colectomy and at predefined clinical visits
at 1 month, 3 months, 6 months and 12 months after IPAA. The predominant
microbiota was analysed using community profiling with denaturing gradient gel
electrophoresis followed by quantitative real-time PCR validation. RESULTS:
Cluster analysis before colectomy distinguished patients with pouchitis from
those with normal pouch during the 1st year of follow-up. In patients developing
pouchitis, an increase of Ruminococcus gnavus (p<0.001), Bacteroides vulgatus
(p=0.043), Clostridium perfringens (p=0.011) and a reduction of two
Lachnospiraceae genera (Blautia (p=0.04), Roseburia (p=0.008)) was observed. A
score combining these five bacterial risk factors was calculated and presence of
at least two risk factors showed a sensitivity and specificity of 100% and 63.6%,
respectively. CONCLUSIONS: Presence of R. gnavus, B. vulgatus and C. perfringens
and absence of Blautia and Roseburia in faecal samples of patients with UC before
surgery is associated with a higher risk of pouchitis after IPAA. Our findings
suggest new predictive and therapeutic strategies in patients undergoing
colectomy with IPAA.
PMID- 26423114
TI - Changes of intracellular Ca2+ in quercetin-induced autophagy progression.
AB - Quercetin was previously reported to exhibit significant anti-proliferative
activities, and its major effect on tumors was to induce cell apoptosis or
autophagy. However, the specific mechanism remains controversial. In this study,
autophagy induced by quercetin was determined with various methods. Intracellular
Ca2+ ([Ca2+]i) was measured after being incubated with Fluo-3 acetoxymethyl (AM).
At the same time, the relationship between the intracellular Ca2+ and autophagy
induced by quercetin was further analyzed. These results showed that autophagy
induced by quercetin (0-50 ug/ml) in HepG2 cells was in a dose-dependent manner.
Meanwhile, when autophagy was induced by quercetin, [Ca2+]i was significantly
increased. And after being incubated with calcium chelator 1,2-bis(2
aminophenoxy)ethane-N,N,N',N-tetraacetic acid-AM, autophagy was suppressed, which
implied that [Ca2+]i elevation appeared to be the cause for autophagy induction.
These results suggested that calcium from intracellular calcium storage may play
an important role in quercetin-induced autophagy.
PMID- 26423115
TI - H2S protects PC12 cells against toxicity of corticosterone by modulation of BDNF
TrkB pathway.
AB - Corticosterone, one of the glucocorticoids, is toxic to neurons and plays an
important role in depressive-like behavior and depression. We previously showed
that hydrogen sulfide (H2S), a novel physiological mediator, plays an inhibitory
role in depression. However, the mechanism underlying H2S-triggered
antidepressant-like role is not clearly known. Brain-derived neurotrophic factor
(BDNF), a neurotrophic factor, plays a neuroprotective role that is mediated by
its high-affinity tropomysin-related kinase B (TrkB) receptor. In this study, to
investigate the underlying mechanism of H2S-induced antidepressant-like role, we
explored whether H2S could protect neurons against corticosterone-mediated
cyctotoxicity and whether this protective role of H2S was involved in the
regulation of BDNF-TrkB pathway. Our data demonstrated that sodium hydrosulfide
(NaHS), the donor of H2S, could prevent corticosterone-induced cytotoxicity,
apoptosis, accumulation of intracellular reactive oxygen species (ROS) and loss
of mitochondrial membrane potential (MMP) in PC12 cells. NaHS not only induced
the up-regulation of BDNF but also prevented the down-regulation of BDNF by
corticosterone. It was also found that blocking BDNF-TrkB pathway by K252a, an
inhibitor of TrkB, abolished the protection of H2S against corticosterone-induced
cytotoxicity, apoptosis, accumulation of ROS, and loss of MMP. These results
suggest that H2S protects against the neurotoxicity of corticosterone by
modulation of the BDNF-TrkB pathway.
PMID- 26423116
TI - C-terminal extension of calmodulin-like 3 protein from Oryza sativa L.:
interaction with a high mobility group target protein.
AB - A large number of calmodulin-like (CML) proteins are present in plants, but there
is little detailed information on the functions of these proteins in rice (Oryza
sativa L.). Here, the CML3 protein from rice (OsCML3) and its truncated form
lacking the C-terminal extension (OsCML3m) were found to exhibit a Ca2+-binding
property and subsequent conformational change, but the ability to bind the CaM
kinase II peptide was only observed for OsCML3m. Changes in their secondary
structure upon Ca2+-binding measured by circular dichroism revealed that OsCML3m
had a higher helical content than OsCML3. Moreover, OsCML3 was mainly localized
in the plasma membrane, whereas OsCML3m was found in the nucleus. The rice high
mobility group B1 (OsHMGB1) protein was identified as one of the putative OsCML3
target proteins. Bimolecular fluorescence complementation analysis revealed that
OsHMGB1 bound OsCML3, OsCML3m or OsCML3s (cysteine to serine mutation at the
prenylation site) in the nucleus presumably through the methionine and
phenylalanine-rich hydrophobic patches, confirming that OsHMGB1 is a target
protein in planta. The effect of OsCML3 or OsCML3m on the DNA-binding ability of
OsHMGB1 was measured using an electrophoretic mobility shift assay. OsCML3m
decreased the level of OsHMGB1 binding to pUC19 double-stranded DNA whereas
OsCML3 did not. Taken together, OsCML3 probably provides a mechanism for
manipulating the DNA-binding ability of OsHMGB1 in the nucleus and its C-terminal
extension provides an intracellular Ca2+ regulatory switch.
PMID- 26423117
TI - Development of Novel Polymeric Prodrugs Synthesized by Mechanochemical Solid
State Copolymerization of Hydroxyethylcellulose and Vinyl Monomers.
AB - Novel polymeric prodrugs were synthesized by mechanochemical solid-state
copolymerization of hydroxyethylcellulose and the methacryloyloxy derivative of 5
fluorouracil (5-FU). Copolymerization was about 94% complete after 4 h, and the
polymeric prodrug was quantitatively obtained after 14 h of reaction. The number
average molecular weight (Mn) and polydispersity (H) of the polymeric prodrug
were 39000 g/mol and 6.20, respectively. Mechanical fracturing of the polymer in
a stainless steel twin-shell blender improved these properties (Mn=16000 g/mol
and H=1.94). 5-FU was sustainably released from the polymeric prodrugs, and the
rate was not affected by the molecular weight or molecular weight distribution of
the prodrug under the experimental conditions used. These results suggest that
novel polymeric prodrugs composed of a polysaccharide and a synthetic polymer can
be fabricated by mechanochemical solid-state copolymerization under anaerobic
conditions.
PMID- 26423118
TI - Copper N-Heterocyclic Carbene Complexes As Active Catalysts for the Synthesis of
2-Substituted Oxazolines from Nitriles and Aminoalcohols.
AB - The reaction between nitriles and aminoalcohols to access 2-substituted
oxazolines was investigated. Using copper-NHC complexes, various nitriles were
successfully converted into the corresponding oxazolines, under milder and less
wasteful conditions than those of previously reported methods.
PMID- 26423120
TI - Diamond-Based Supercapacitors: Realization and Properties.
AB - In this Spotlight on Applications, we describe our recent progress on the
fabrication of surface-enlarged boron-doped polycrystalline diamond electrodes,
and evaluate their performance in supercapacitor applications. We begin with a
discussion of the fabrication methods of porous diamond materials. The diamond
surface enlargement starts with a top-down plasma etching method. Although the
extra surface area provided by surface roughening or nanostructuring provides
good outcome for sensing applications, a capacitance value <1 mF cm-2 or a
surface-enlargement factor <100 fail to meet the requirement of a practical
supercapacitor. Driven by the need for large surface areas, we recently focused
on the tempated-growth method. We worked on both supported and free-standing
porous diamond materials to enhance the areal capacitance to the "mF cm-2" range.
With our newly developed free-standing diamond paper, areal capacitance can be
multiplied by stacking multilayers of the electrode material. Finally,
considering the fact that there is no real diamond-based supercapacitor device up
to now, we fabricated the first prototype pouch-cell device based on the free
standing diamond paper to evaluate its performance. The results reveal that the
diamond paper is suitable for operation in high potential windows (up to 2.5 V)
in aqueous electrolyte with a capacitance of 0.688 mF cm-2 per layer of paper (or
0.645 F g-1). Impedance spectroscopy revealed that the operation frequency of the
device exceeds 30 Hz. Because of the large potential window and the ability to
work at high frequency, the specific power of the device reached 1 * 105 W kg-1.
In the end, we made estimations on the future target performance of diamond
supercapacitors based on the existing information.
PMID- 26423119
TI - Advancing Urinary Protein Biomarker Discovery by Data-Independent Acquisition on
a Quadrupole-Orbitrap Mass Spectrometer.
AB - The promises of data-independent acquisition (DIA) strategies are a comprehensive
and reproducible digital qualitative and quantitative record of the proteins
present in a sample. We developed a fast and robust DIA method for comprehensive
mapping of the urinary proteome that enables large scale urine proteomics
studies. Compared to a data-dependent acquisition (DDA) experiments, our DIA
assay doubled the number of identified peptides and proteins per sample at half
the coefficients of variation observed for DDA data (DIA = ~8%; DDA = ~16%). We
also tested different spectral libraries and their effects on overall protein and
peptide identifications and their reproducibilities, which provided clear
evidence that sample type-specific spectral libraries are preferred for reliable
data analysis. To show applicability for biomarker discovery experiments, we
analyzed a sample set of 87 urine samples from children seen in the emergency
department with abdominal pain. The whole set was analyzed with high proteome
coverage (~1300 proteins/sample) in less than 4 days. The data set revealed
excellent biomarker candidates for ovarian cyst and urinary tract infection. The
improved throughput and quantitative performance of our optimized DIA workflow
allow for the efficient simultaneous discovery and verification of biomarker
candidates without the requirement for an early bias toward selected proteins.
PMID- 26423122
TI - Evaluation of a focussed protocol for hand-held echocardiography and computer
assisted auscultation in detecting latent rheumatic heart disease in scholars.
AB - Introduction Echocardiography is the diagnostic test of choice for latent
rheumatic heart disease. The utility of echocardiography for large-scale
screening is limited by high cost, complex diagnostic protocols, and time to
acquire multiple images. We evaluated the performance of a brief hand-held
echocardiography protocol and computer-assisted auscultation in detecting latent
rheumatic heart disease with or without pathological murmur. METHODS: A total of
27 asymptomatic patients with latent rheumatic heart disease based on the World
Heart Federation criteria and 66 healthy controls were examined by standard
cardiac auscultation to detect pathological murmur. Hand-held echocardiography
using a focussed protocol that utilises one view - that is, the parasternal long
axis view - and one measurement - that is, mitral regurgitant jet - and a
computer-assisted auscultation utilising an automated decision tool were
performed on all patients. RESULTS: The sensitivity and specificity of computer
assisted auscultation in latent rheumatic heart disease were 4% (95% CI 1.0
20.4%) and 93.7% (95% CI 84.5-98.3%), respectively. The sensitivity and
specificity of the focussed hand-held echocardiography protocol for definite
rheumatic heart disease were 92.3% (95% CI 63.9-99.8%) and 100%, respectively.
The test reliability of hand-held echocardiography was 98.7% for definite and
94.7% for borderline disease, and the adjusted diagnostic odds ratios were 1041
and 263.9 for definite and borderline disease, respectively. CONCLUSION: Computer
assisted auscultation has extremely low sensitivity but high specificity for
pathological murmur in latent rheumatic heart disease. Focussed hand-held
echocardiography has fair sensitivity but high specificity and diagnostic utility
for definite or borderline rheumatic heart disease in asymptomatic patients.
PMID- 26423121
TI - Corticocortical connection patterns reveal two distinct visual cortical areas
bordering dorsal V2 in marmoset monkey.
AB - The organization of the cortex located immediately anterior to the second visual
area (V2), i.e., the third tier visual cortex, remains controversial, especially
in New World primates. In particular, there is lack of consensus regarding the
exact location and extent of the lower visual quadrant representation of the
third visual area V3 (or ventrolateral posterior -VLP - of a different
nomenclature). Microelectrode and connectional mapping studies have revealed the
existence of an upper visual quadrant representation abutting dorsal V2
anteriorly, and bordered medially and laterally by representations of the lower
visual quadrant. It remains unclear whether these lower field regions are both
part of a single area V3, which is split into two patches by an interposed region
of upper field representation, or whether they are the lower field
representations of two different areas, the dorsomedial area (DM) and area
V3/VLP, respectively. To address this question, we quantitatively analyzed the
patterns of corticocortical afferent connections labeled by tracer injections
targeted to these two lower field regions in the dorsal aspect of the third tier
cortex. We found different inter-areal connectivity patterns arising from these
two regions, strongly suggesting that they belong to two different visual areas.
In particular, our results indicate that the dorsal aspect of the third tier
cortex consists of two distinct areas: a full area DM, representing the lower
quadrant medially, and the upper quadrant laterally, and the lower quadrant
representation of V3/VLP, located laterally to upper field DM. DM is
predominantly connected with areas of the dorsal visual stream, and V3/VLP with
areas of the ventral stream. These results prompt further functional
investigations of the third tier cortex, as previous studies of this cortical
territory may have pooled response properties of two very different areas into a
single area V3.
PMID- 26423123
TI - Extracellular Vesicles from Bovine Follicular Fluid Support Cumulus Expansion.
AB - Expansion of the cumulus complex surrounding the oocyte is critical for ovulation
of a fertilizable egg. The ovulation-inducing surge of luteinizing hormone leads
to an increased expression of genes such as prostaglandin-endoperoxide synthase 2
(Ptgs2), pentraxin-related protein 3 (Ptx3), and tumor necrosis factor alpha
induced protein 6 (Tnfaip6) that support cumulus expansion. Factors released by
mural granulosa and cumulus granulosa cells into the follicular fluid induce
paracrine signaling within the follicular compartment. The follicular fluid that
separates these distinct granulosa cell types is an enriched fluid containing
numerous proteins, nucleic acids, and other macromolecules. Extracellular
vesicles (EVs) are also present; however, no physiologically relevant functions
of follicular EVs have yet been demonstrated. In our study, the effect of
follicular EVs on cumulus-oocyte complex (COC) expansion and relevant gene
expression was assayed. Follicular EVs were isolated using ultracentrifugation
from follicular fluid of small (3-5 mm) and large (>9 mm) antral bovine
follicles, then characterized by nanoparticle tracking analysis, electron
microscopy, and Western blot analysis. To test for bioactivity, mouse and bovine
COCs were cultured with follicular EVs. Cumulus expansion and Ptgs2, Ptx3, and
Tnfaip6 gene expression were measured following COC maturation culture. The
results demonstrated that follicular EVs can support both measurable cumulus
expansion and increased gene expression.
PMID- 26423124
TI - How Is the Number of Primordial Follicles in the Ovarian Reserve Established?
AB - The number of primordial follicles in the ovarian reserve is an important
determinant of the length of the ovarian lifespan, and therefore the fertility of
an individual. This reserve contains all of the oocytes potentially available for
fertilization throughout the fertile lifespan. The maximum number is set during
pregnancy or just after birth in most mammalian species; current evidence does
not support neofolliculogenesis after the ovarian reserve is established,
although this is increasingly being reexamined. Under physiological
circumstances, this number will be influenced by the number of primordial germ
cells initially specified in the epiblast of the developing embryo, their
proliferation during and after migration to the developing gonads, and their
death during oogenesis and formation of primordial follicles at nest breakdown.
Death of germ cells during the establishment of the ovarian reserve occurs
principally by autophagy or apoptosis, although the triggers that initiate these
remain elusive. This review outlines the regulatory steps that determine the
number of primordial follicles and thus the number of oocytes in the ovarian
reserve at birth, using the mouse as the model, interspersed with human data
where available. This information has application for understanding the
variability in duration of fertility that occurs between normal individuals and
with age, in premature ovarian insufficiency, and after chemotherapy or
radiotherapy.
PMID- 26423125
TI - Involvement of Mitochondrial Activity and OXPHOS in ATP Synthesis During the
Motility Phase of Spermatozoa in the Pacific Oyster, Crassostrea gigas.
AB - In the Pacific oyster, spermatozoa are characterized by a remarkably long
movement phase (i.e., over 24 h) sustained by a capacity to maintain
intracellular ATP level. To gain information on oxidative phosphorylation
(OXPHOS) functionality during the motility phase of Pacific oyster spermatozoa,
we studied 1) changes in spermatozoal mitochondrial activity, that is,
mitochondrial membrane potential (MMP), and intracellular ATP content in relation
to motion parameters and 2) the involvement of OXPHOS for spermatozoal movement
using carbonyl cyanide m-chlorophenyl hydrazone (CCCP). The percentage of motile
spermatozoa decreased over a 24 h movement period. MMP increased steadily during
the first 9 h of the movement phase and was subsequently maintained at a constant
level. Conversely, spermatozoal ATP content decreased steadily during the first 9
h postactivation and was maintained at this level during the following hours of
the movement phase. When OXPHOS was decoupled by CCCP, the movement of
spermatozoa was maintained 2 h and totally stopped after 4 h of incubation,
whereas spermatozoa were still motile in the control after 4 h. Our results
suggest that the ATP sustaining flagellar movement of spermatozoa may partially
originate from glycolysis or from mobilization of stored ATP or from potential
phosphagens during the first 2 h of movement as deduced by the decoupling by CCCP
of OXPHOS. However, OXPHOS is required to sustain the long motility phase of
Pacific oyster spermatozoa. In addition, spermatozoa may hydrolyze intracellular
ATP content during the early part of the movement phase, stimulating
mitochondrial activity. This stimulation seems to be involved in sustaining a
high ATP level until the end of the motility phase.
PMID- 26423126
TI - A Whole-Mount Approach for Accurate Quantitative and Spatial Assessment of Fetal
Oocyte Dynamics in Mice.
AB - Depletion of oocytes from the embryonic ovary is a key feature of mammalian
oogenesis; however, the rational and molecular bases for this phenomenon remain
poorly understood. Presently in the field, the most systematic analysis used to
understand the effect of a given molecular pathway on fetal oocyte attrition is
to count the number of oocytes in ovaries at different stages of development.
This analysis is commonly done using a sampling method based on sectioning of the
ovary, a technique that includes many laborious steps culminating in an
inaccurate estimate of oocyte number contained within that ovary. This inability
to generate data that are directly comparable between labs hinders the field and
raises questions about the timing and rate of oocyte depletion. Therefore, we set
out to implement a robust method that can be easily used by most research
laboratories to study the dynamics of oogenesis during fetal mouse ovary
development in both normal and experimental conditions. Here we describe an
approach to accurately count the total number of oocytes in embryonic ovaries.
This method is based on whole-mount immunofluorescence, tissue clearing with
sucrose and ScaleA2 reagent, and automatic detection and counting of germ cells
in intact ovaries using confocal microscopy and three-dimensional software
analyses. We demonstrate the power of the method by assessing variation of fetal
oocyte numbers between left and right ovaries and between litters of mice.
Finally, we anticipate that the method could be adopted to the analysis of
substages of meiotic prophase I and ovarian somatic cells.
PMID- 26423127
TI - Involvement of Receptor Activity-Modifying Protein 3 (RAMP3) in the Vascular
Actions of Adrenomedullin in Rat Mesenteric Artery Smooth Muscle Cells.
AB - CALCB, ADM, and ADM2 are potent vasodilators that share a seven-transmembrane
GPCR, calcitonin receptor-like receptor (CALCRL), whose ligand specificity is
dictated by the presence of one of the three receptor activity-modifying proteins
(RAMPs). We assessed the relative pharmacologic potency of these peptides in
mesenteric artery smooth muscle cells (VSMCs) and the specific RAMP that mediates
the effect of ADM in VSMCs. VSMCs, with or without RAMP knockdown, were treated
with CALCB, ADM, or ADM2 in the presence or absence of their antagonists, CALCB8
37, ADM22-52, and ADM217-47, respectively, to assess the relative effect of
peptides on cAMP production and their pharmacologic potency. Proximity ligation
assay was used to assess the specific RAMP that associates with CALCRL to mediate
the actions of ADM in VSMCs. All three peptides induced cAMP generation in VSMCs
and the order of their potency is CALCB > ADM > ADM2. Effects of CALCB were
blocked by CALCB8-37, ADM effects were blocked by CALCB8-37 and ADM217-47 but not
ADM22-52, and ADM2 effects were blocked by all three antagonists. Knockdown of
RAMP2 was ineffective, whereas knockdown of RAMP3 inhibited ADM-induced cAMP
production in VSMCs, suggesting involvement of RAMP3 with CALCRL to mediate ADM
effects. Absence of both RAMP2 and RAMP3 further increased CALCB-induced cAMP
synthesis compared to control (P < 0.05). ADM increased CALCRL and RAMP3
association and RAMP3 knockdown inhibited the interaction of ADM with CALCRL.
PMID- 26423128
TI - Global multiple protein-protein interaction network alignment by combining
pairwise network alignments.
AB - BACKGROUND: A wealth of protein interaction data has become available in recent
years, creating an urgent need for powerful analysis techniques. In this context,
the problem of finding biologically meaningful correspondences between different
protein-protein interaction networks (PPIN) is of particular interest. The PPIN
of a species can be compared with that of other species through the process of
PPIN alignment. Such an alignment can provide insight into basic problems like
species evolution and network component function determination, as well as
translational problems such as target identification and elucidation of
mechanisms of disease spread. Furthermore, multiple PPINs can be aligned
simultaneously, expanding the analytical implications of the result. While there
are several pairwise network alignment algorithms, few methods are capable of
multiple network alignment. RESULTS: We propose SMAL, a MNA algorithm based on
the philosophy of scaffold-based alignment. SMAL is capable of converting results
from any global pairwise alignment algorithms into a MNA in linear time. Using
this method, we have built multiple network alignments based on combining
pairwise alignments from a number of publicly available (pairwise) network
aligners. We tested SMAL using PPINs of eight species derived from the IntAct
repository and employed a number of measures to evaluate performance.
Additionally, as part of our experimental investigations, we compared the
effectiveness of SMAL while aligning up to eight input PPINs, and examined the
effect of scaffold network choice on the alignments. CONCLUSIONS: A key advantage
of SMAL lies in its ability to create MNAs through the use of pairwise network
aligners for which native MNA implementations do not exist. Experiments indicate
that the performance of SMAL was comparable to that of the native MNA
implementation of established methods such as IsoRankN and SMETANA. However, in
terms of computational time, SMAL was significantly faster. SMAL was also able to
retain many important characteristics of the native pairwise alignments, such as
the number of aligned nodes and edges, as well as the functional and homologene
similarity of aligned nodes. The speed, flexibility and the ability to retain
prior correspondences as new networks are aligned, makes SMAL a compelling choice
for alignment of multiple large networks.
PMID- 26423130
TI - The gut-brain axis: interactions between Helicobacter pylori and enteric and
central nervous systems.
PMID- 26423129
TI - Role of Diffusion Tensor MR Imaging in Degenerative Cervical Spine Disease: a
Review of the Literature.
AB - In the article we review the current role of diffusion tensor imaging (DTI), a
modern magnetic resonance (MR) technique, in the diagnosis and the management of
cervical spondylotic myelopathy (CSM), the most serious complication of
degenerative cervical spine disease (DCSD). The pathogenesis of DCSD is presented
first with an emphasis placed on the pathological processes leading to myelopathy
development. An understanding of the pathophysiological background of DCSD is
necessary for appropriate interpretation of MR images, both plain and DTI.
Conventional MRI is currently the imaging modality of choice in DCSD and provides
useful information concerning the extent of spondylotic changes and degree of
central spinal canal stenosis; however its capability in myelopathy detection is
limited. DTI is a state of the art imaging method which recently has emerged in
spinal cord investigations and has the potential to detect microscopic
alterations which are beyond the capability of plain MRI. In the article we
present the physical principles underlying DTI which determine its sensitivity,
followed by an overview of technical aspects of DTI acquisition with a special
consideration of spinal cord imaging. Finally, the scientific reports concerning
DTI utility in DSCD are also reviewed. DTI detects spinal cord injury in the
course of DCSD earlier than any other method and could be useful in predicting
surgical outcomes in CMS patients, however technical and methodology improvement
as well as standardization of acquisition protocols and postprocessing methods
among the imaging centers are needed before its implementation in clinical
practice.
PMID- 26423131
TI - Allocation of freshly assimilated carbon into primary and secondary metabolites
after in situ 13C pulse labelling of Norway spruce (Picea abies).
AB - Plants allocate carbon (C) to sink tissues depending on phenological,
physiological or environmental factors. We still have little knowledge on C
partitioning into various cellular compounds and metabolic pathways at various
ecophysiological stages. We used compound-specific stable isotope analysis to
investigate C partitioning of freshly assimilated C into tree compartments
(needles, branches and stem) as well as into needle water-soluble organic C
(WSOC), non-hydrolysable structural organic C (stOC) and individual chemical
compound classes (amino acids, hemicellulose sugars, fatty acids and alkanes) of
Norway spruce (Picea abies) following in situ (13)C pulse labelling 15 days after
bud break. The (13)C allocation within the above-ground tree biomass demonstrated
needles as a major C sink, accounting for 86% of the freshly assimilated C 6 h
after labelling. In needles, the highest allocation occurred not only into the
WSOC pool (44.1% of recovered needle (13)C) but also into stOC (33.9%). Needle
growth, however, also caused high (13)C allocation into pathways not involved in
the formation of structural compounds: (i) pathways in secondary metabolism, (ii)
C-1 metabolism and (iii) amino acid synthesis from photorespiration. These
pathways could be identified by a high (13)C enrichment of their key amino acids.
In addition, (13)C was strongly allocated into the n-alkyl lipid fraction (0.3%
of recovered (13)C), whereby (13)C allocation into cellular and cuticular
exceeded that of epicuticular fatty acids. (13)C allocation decreased along the
lipid transformation and translocation pathways: the allocation was highest for
precursor fatty acids, lower for elongated fatty acids and lowest for the
decarbonylated n-alkanes. The combination of (13)C pulse labelling with compound
specific (13)C analysis of key metabolites enabled tracing relevant C allocation
pathways under field conditions. Besides the primary metabolism synthesizing
structural cell compounds, a complex network of pathways consumed the assimilated
(13)C and kept most of the assimilated C in the growing needles.
PMID- 26423133
TI - Isolation and characterization of a subgroup IIa WRKY transcription factor
PtrWRKY40 from Populus trichocarpa.
AB - Salicylic acid (SA) is a defense-related key signaling molecule involved in plant
immunity. In this study, a subgroup IIa WRKY gene PtrWRKY40 was isolated from
Populus trichocarpa, which displayed amino acid sequence similar to Arabidopsis
AtWRKY40, AtWRKY18 and AtWRKY60. PtrWRKY40 transcripts accumulated significantly
in response to SA, methyl jasmonate and hemibiotrophic fungus Dothiorella
gregaria Sacc. Overexpression of PtrWRKY40 in transgenic poplar conferred higher
susceptibility to D. gregaria infection. This susceptibility was coupled with
reduced expression of SA-associated genes (PR1.1, PR2.1, PR5.9, CPR5 and SID2)
and jasmonic acid (JA)-related gene JAZ8. Decreased accumulation of endogenous SA
was observed in transgenic lines overexpressing PtrWRKY40 when compared with wild
type plants. However, constitutive expression of PtrWRKY40 in Arabidopsis
thaliana displayed resistance to necrotrophic fungus Botrytis cinerea, and the
expression of JA-defense-related genes such as PDF1.2, VSP2 and PR3 was
remarkably increased in transgenic plants upon infection with fugal pathogens.
Together, our findings indicate that PtrWRKY40 plays a negative role in
resistance to hemibiotrophic fungi in poplar but functions as a positive
regulator of resistance toward the necrotrophic fungi in Arabidopsis.
PMID- 26423132
TI - Non-structural carbohydrates in woody plants compared among laboratories.
AB - Non-structural carbohydrates (NSC) in plant tissue are frequently quantified to
make inferences about plant responses to environmental conditions. Laboratories
publishing estimates of NSC of woody plants use many different methods to
evaluate NSC. We asked whether NSC estimates in the recent literature could be
quantitatively compared among studies. We also asked whether any differences
among laboratories were related to the extraction and quantification methods used
to determine starch and sugar concentrations. These questions were addressed by
sending sub-samples collected from five woody plant tissues, which varied in NSC
content and chemical composition, to 29 laboratories. Each laboratory analyzed
the samples with their laboratory-specific protocols, based on recent
publications, to determine concentrations of soluble sugars, starch and their
sum, total NSC. Laboratory estimates differed substantially for all samples. For
example, estimates for Eucalyptus globulus leaves (EGL) varied from 23 to 116
(mean = 56) mg g(-1) for soluble sugars, 6-533 (mean = 94) mg g(-1) for starch
and 53-649 (mean = 153) mg g(-1) for total NSC. Mixed model analysis of variance
showed that much of the variability among laboratories was unrelated to the
categories we used for extraction and quantification methods (method category
R(2) = 0.05-0.12 for soluble sugars, 0.10-0.33 for starch and 0.01-0.09 for total
NSC). For EGL, the difference between the highest and lowest least squares means
for categories in the mixed model analysis was 33 mg g(-1) for total NSC,
compared with the range of laboratory estimates of 596 mg g(-1). Laboratories
were reasonably consistent in their ranks of estimates among tissues for starch
(r = 0.41-0.91), but less so for total NSC (r = 0.45-0.84) and soluble sugars (r
= 0.11-0.83). Our results show that NSC estimates for woody plant tissues cannot
be compared among laboratories. The relative changes in NSC between treatments
measured within a laboratory may be comparable within and between laboratories,
especially for starch. To obtain comparable NSC estimates, we suggest that users
can either adopt the reference method given in this publication, or report
estimates for a portion of samples using the reference method, and report
estimates for a standard reference material. Researchers interested in NSC
estimates should work to identify and adopt standard methods.
PMID- 26423134
TI - Defective sister chromatid cohesion is synthetically lethal with impaired APC/C
function.
AB - Warsaw breakage syndrome (WABS) is caused by defective DDX11, a DNA helicase that
is essential for chromatid cohesion. Here, a paired genome-wide siRNA screen in
patient-derived cell lines reveals that WABS cells do not tolerate partial
depletion of individual APC/C subunits or the spindle checkpoint inhibitor
p31(comet). A combination of reduced cohesion and impaired APC/C function also
leads to fatal mitotic arrest in diploid RPE1 cells. Moreover, WABS cell lines,
and several cancer cell lines with cohesion defects, display a highly increased
response to a new cell-permeable APC/C inhibitor, apcin, but not to the spindle
poison paclitaxel. Synthetic lethality of APC/C inhibition and cohesion defects
strictly depends on a functional mitotic spindle checkpoint as well as on intact
microtubule pulling forces. This indicates that the underlying mechanism involves
cohesion fatigue in response to mitotic delay, leading to spindle checkpoint re
activation and lethal mitotic arrest. Our results point to APC/C inhibitors as
promising therapeutic agents targeting cohesion-defective cancers.
PMID- 26423136
TI - Demonstration of self-truncated ionization injection for GeV electron beams.
AB - Ionization-induced injection mechanism was introduced in 2010 to reduce the laser
intensity threshold for controllable electron trapping in laser wakefield
accelerators (LWFA). However, usually it generates electron beams with continuous
energy spectra. Subsequently, a dual-stage target separating the injection and
acceleration processes was regarded as essential to achieve narrow energy-spread
electron beams by ionization injection. Recently, we numerically proposed a self
truncation scenario of the ionization injection process based upon overshooting
of the laser-focusing in plasma which can reduce the electron injection length
down to a few hundred micrometers, leading to accelerated beams with extremely
low energy-spread in a single-stage. Here, using 100 TW-class laser pulses we
report experimental observations of this injection scenario in centimeter-long
plasma leading to the generation of narrow energy-spread GeV electron beams,
demonstrating its robustness and scalability. Compared with the self-injection
and dual-stage schemes, the self-truncated ionization injection generates higher
quality electron beams at lower intensities and densities, and is therefore
promising for practical applications.
PMID- 26423135
TI - The lethal response to Cdk1 inhibition depends on sister chromatid alignment
errors generated by KIF4 and isoform 1 of PRC1.
AB - Cyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division.
Complete ablation of Cdk1 precludes the entry of G2 phase cells into mitosis, and
is early embryonic lethal in mice. Dampening Cdk1 activation, by reducing gene
expression or upon treatment with cell-permeable Cdk1 inhibitors, is also
detrimental for proliferating cells, but has been associated with defects in
mitotic progression, and the formation of aneuploid daughter cells. Here, we used
a large-scale RNAi screen to identify the human genes that critically determine
the cellular toxicity of Cdk1 inhibition. We show that Cdk1 inhibition leads to
fatal sister chromatid alignment errors and mitotic arrest in the spindle
checkpoint. These problems start early in mitosis and are alleviated by depletion
of isoform 1 of PRC1 (PRC1-1), by gene ablation of its binding partner KIF4, or
by abrogation of KIF4 motor activity. Our results show that, normally, Cdk1
activity must rise above the level required for mitotic entry. This prevents KIF4
dependent PRC1-1 translocation to astral microtubule tips and safeguards proper
chromosome congression. We conclude that cell death in response to Cdk1
inhibitors directly relates to chromosome alignment defects generated by
insufficient repression of PRC1-1 and KIF4 during prometaphase.
PMID- 26423137
TI - The recombinant expression and activity detection of MAF-1 fusion protein.
AB - This study establishes the recombinant expression system of MAF-1 (Musca
domestica antifungal peptide-1) and demonstrates the antifungal activity of the
expression product and shows the relationship between biological activity and
structure. The gene segments on mature peptide part of MAF-1 were cloned, based
on the primers designed according to the cDNA sequence of MAF-1. We constructed
the recombinant prokaryotic expression plasmid using prokaryotic expression
vector (pET-28a(+)) and converted it to the competent cell of BL21(DE3) to gain
recombinant MAF-1 fusion protein with His tag sequence through purifying affinity
chromatographic column of Ni-NTA. To conduct the Western Blotting test,
recombinant MAF-1 fusion protein was used to produce the polyclonal antibody of
rat. The antifungal activity of the expression product was detected using Candida
albicans (ATCC10231) as the indicator. The MAF-1 recombinant fusion protein was
purified to exhibit obvious antifungal activity, which lays the foundation for
the further study of MAF-1 biological activity, the relationship between
structure and function, as well as control of gene expression.
PMID- 26423138
TI - Comparative proteomics reveals human pluripotent stem cell-derived limbal
epithelial stem cells are similar to native ocular surface epithelial cells.
AB - Limbal epithelial stem cells (LESCs) are tissue-specific stem cells responsible
for renewing the corneal epithelium. Acute trauma or chronic disease affecting
LESCs may disrupt corneal epithelial renewal, causing vision threatening and
painful ocular surface disorders, collectively referred to as LESC deficiency
(LESCD). These disorders cannot be treated with traditional corneal
transplantation and therefore alternative cell sources for successful cell-based
therapy are needed. LESCs derived from human pluripotent stem cells (hPSCs) are a
prospective source for ocular surface reconstruction, yet critical evaluation of
these cells is crucial before considering clinical applications. In order to
quantitatively evaluate hPSC-derived LESCs, we compared protein expression in
native human corneal cells to that in hPSC-derived LESCs using isobaric tag for
relative and absolute quantitation (iTRAQ) technology. We identified 860 unique
proteins present in all samples, including proteins involved in cell cycling,
proliferation, differentiation and apoptosis, various LESC niche components, and
limbal and corneal epithelial markers. Protein expression profiles were nearly
identical in LESCs derived from two different hPSC lines, indicating that the
differentiation protocol is reproducible, yielding homogeneous cell populations.
Their protein expression profile suggests that hPSC-derived LESCs are similar to
the human ocular surface epithelial cells, and possess LESC-like characteristics.
PMID- 26423140
TI - Detailed classification of swimming paths in the Morris Water Maze: multiple
strategies within one trial.
AB - The Morris Water Maze is a widely used task in studies of spatial learning with
rodents. Classical performance measures of animals in the Morris Water Maze
include the escape latency, and the cumulative distance to the platform. Other
methods focus on classifying trajectory patterns to stereotypical classes
representing different animal strategies. However, these approaches typically
consider trajectories as a whole, and as a consequence they assign one full
trajectory to one class, whereas animals often switch between these strategies,
and their corresponding classes, within a single trial. To this end, we take a
different approach: we look for segments of diverse animal behaviour within one
trial and employ a semi-automated classification method for identifying the
various strategies exhibited by the animals within a trial. Our method allows us
to reveal significant and systematic differences in the exploration strategies of
two animal groups (stressed, non-stressed), that would be unobserved by earlier
methods.
PMID- 26423139
TI - NFkappaB signaling drives pro-granulocytic astroglial responses to neuromyelitis
optica patient IgG.
AB - BACKGROUND: Astrocytes expressing the aquaporin-4 water channel are a primary
target of pathogenic, disease-specific immunoglobulins (IgG) found in patients
with neuromyelitis optica (NMO). Immunopathological analyses of active NMO
lesions highlight a unique inflammatory phenotype marked by infiltration of
granulocytes. Previous studies characterized this granulocytic infiltrate as a
response to vasculocentric complement activation and localized tissue
destruction. In contrast, we observe that granulocytic infiltration in NMO
lesions occurs independently of complement-mediated tissue destruction or active
demyelination. These immunopathological findings led to the hypothesis that NMO
IgG stimulates astrocyte signaling that is responsible for granulocytic
recruitment in NMO. METHODS: Histopathology was performed on archival formalin
fixed paraffin-embedded autopsy-derived CNS tissue from 23 patients clinically
and pathologically diagnosed with NMO or NMO spectrum disorder. Primary murine
astroglial cultures were stimulated with IgG isolated from NMO patients or
control IgG from healthy donors. Transcriptional responses were assessed by
microarray, and translational responses were measured by ELISA. Signaling through
the NFkappaB pathway was measured by western blotting and immunostaining.
RESULTS: Stimulation of primary murine astroglial cultures with NMO IgG elicited
a reactive and inflammatory transcriptional response that involved signaling
through the canonical NFkappaB pathway. This signaling resulted in the release of
pro-granulocytic chemokines and was inhibited by the clinically relevant
proteasome inhibitors bortezomib and PR-957. CONCLUSIONS: We propose that the
astrocytic NFkappaB-dependent inflammatory response to stimulation by NMO IgG
represents one of the earliest events in NMO pathogenesis, providing a target for
therapeutic intervention upstream of irreversible cell death and tissue damage.
PMID- 26423141
TI - Prevalence and association of asthma and allergic sensitization with dietary
factors in schoolchildren: data from the french six cities study.
AB - BACKGROUND: The prevalence of asthma and allergy has recently risen among
children. This increase in prevalence might be related to various factors,
particularly diet. The aim of this study is to assess the prevalence and
association of asthma and allergic sensitization with dietary factors in the
French Six Cities Study. METHODS: Cross-sectional studies were performed among
7432 schoolchildren aged 9-11 years in Bordeaux, Clermont-Ferrand, Creteil,
Marseille, Reims, and Strasbourg. Parental questionnaires, based on the
International Study on Asthma and Allergies in Childhood (ISAAC), were used to
collect information on allergic diseases and potential exposure factors including
a food frequency questionnaire to evaluate dietary habits. Skin prick testing to
common allergens for allergic sensitization and bronchial hyper-responsiveness
(BHR) testing to exercise were performed. Confounders control was performed with
multiple logistic regressions. RESULTS: Asthma symptoms, asthma and allergic
sensitization were more prevalent in boys than in girls and were more prevalent
in the South than in the North of France. After adjustment for confounders, fruit
juice intake was associated with a low prevalence of lifetime asthma (ORa [95 %
CI]; 0.73 [0.56-0.97]), butter intake was positively associated with atopic
wheeze (1.48 [1.07-2.05]) and having lunch at the canteen 1-2 times/week compared
to never or occasionally was associated with a lower prevalence of past year
wheeze (0.71 [0.52-0.96]), lifetime asthma (0.76 [0.60-0.96]) and allergic
sensitization (0.80 [0.67-0.95]). Meat intake was inversely related to past year
wheeze among atopic children (0.68 [0.50-0.98]) while fast food consumption and
butter intake were associated with an increase prevalence of asthma (2.39 [1.47
3.93] and 1.51 [1.17-2.00] respectively). Fish intake was associated with a lower
prevalence of asthma among non-atopic children (0.61 [0.43-0.87]. None of the
dietary factors was associated with BHR. CONCLUSIONS: Diet is associated with
wheeze, asthma and allergic sensitization but not with BHR in children. These
results provide further evidence that adherence to a healthy diet including
fruits, meat and fish seems to have a protective effect on asthma and allergy in
childhood. However, prospective and experimental studies are needed to provide
causal evidence concerning the effect of diet on asthma and atopy.
PMID- 26423143
TI - [Use in France of Baclofen for Alcohol Dependence from 2007 to 2013: Cohort Study
Based on the Databases SNIIRAM and PMSI].
AB - AIM: To quantify and describe the population starting treatment with baclofen for
alcohol dependence during the period 2007-2013 in France. METHODS: The French
national health insurance (systeme national d'information inter-regimes de
l'Assurance maladie [SNIIRAM]) and French hospital discharge (programme de
medicalisation des systemes d'information [PMSI]) databases were used to identify
the population starting treatment with baclofen, determine the algorithm of
baclofen use, define patient characteristics and their treatment. RESULTS: About
200,000 subjects initiated baclofen therapy between 2007 and 2013, for alcohol
dependence in 52.0% of cases. In 2013, this population was predominantly male
(62.3%), with a mean age of 50.1 years, the first prescriber was a general
practitioner in 58.9% of cases, they continued their treatment 6 months after
their initiation in 48.8% of cases and one half of these subjects consumed at
least 57.0 mg of baclofen daily. CONCLUSIONS: The use of baclofen for alcohol
dependence increased considerably since 2008, with more than 34,000 new users and
more than 9,000 general practitioners as first prescribers in 2013.
PMID- 26423142
TI - Acute cardiac injury events <=30 days after laboratory-confirmed influenza virus
infection among U.S. veterans, 2010-2012.
AB - BACKGROUND: Cardiac injury is a known potential complication of influenza
infection. Because U.S. veterans cared for at the U.S. Department of Veterans
Affairs are older and have more cardiovascular disease (CVD) risk factors than
the general U.S. population, veterans are at risk for cardiac complications of
influenza infection. We investigated biomarkers of cardiac injury characteristics
and associated cardiac events among veterans who received cardiac biomarker
testing <=30 days after laboratory-confirmed influenza virus infection. METHODS:
Laboratory-confirmed influenza cases among veterans cared for at U.S. Department
of Veterans Affairs' facilities for October 2010-December 2012 were identified
using electronic medical records (EMRs). Influenza confirmation was based on
respiratory specimen viral culture or antigen or nucleic acid detection. Acute
cardiac injury (ACI) was defined as an elevated cardiac biomarker (troponin I or
creatinine kinase isoenzyme MB) >99 % of the upper reference limit occurring <=30
days after influenza specimen collection. EMRs were reviewed for demographics,
CVD history and risk factors, and ACI-associated cardiac events. RESULTS: Among
38,197 patients with influenza testing results, 4,469 (12 %) had a positive
result; 600 of those patients had cardiac biomarker testing performed <=30 days
after influenza testing, and 143 (24 %) had one or more elevated cardiac
biomarkers. Among these 143, median age was 73 years (range 44-98 years), and 98
(69 %) were non-Hispanic white. All patients had one or more CVD risk factors,
and 98 (69 %) had a history of CVD. Eighty-six percent of ACI-associated events
occurred within 3 days of influenza specimen collection date. Seventy patients
(49 %) had documented or probable acute myocardial infarction, 8 (6 %) acute
congestive heart failure, 6 (4 %) myocarditis, and 4 (3 %) atrial fibrillation.
Eleven (8 %) had non-cardiac explanations for elevated cardiac biomarkers, and 44
(31 %) had no documented explanation. Sixty-eight (48 %) patients had received
influenza vaccination during the related influenza season. CONCLUSION: Among
veterans with laboratory-confirmed influenza infection and cardiac biomarker
testing <=30 days after influenza testing, approximately 25 % had evidence of
ACI, the majority within 3 days. Approximately half were myocardial infarctions.
Our findings emphasize the importance of considering ACI associated with
influenza infection among patients at high risk, including this older population
with prevalent CVD risk factors.
PMID- 26423144
TI - Validation and Reproducibility of the Updated French Causality Assessment Method:
an Evaluation by Pharmacovigilance Centres & Pharmaceutical Companies.
AB - OBJECTIVE: Assess the validity and reproducibility of the updated version of the
French causality assessment method in conditions approaching real-life use.
METHODS: A random sample of 31 drug-event pairs from the French pharmacovigilance
database was assessed by the consensual judgement of three experts (gold
standard). Separately, a team from a pharmacovigilance centre (PhVC) and another
from a pharmaceutical company assessed these pairs using the current method, then
with the updated method. To test the inter- and intra-rater reproducibility, two
seniors and two juniors from a PhVC and a pharmaceutical company assessed the
pairs twice with the updated method. A weighted kappa coefficient was used to
measure the agreement of the two causality assessment methods with the consensual
expert judgement (validity) as well as the agreement of the updated causality
assessment over time (intra-rater reproducibility) and between evaluators (inter
rater reproducibility). RESULTS: Agreement between the current method and
consensual expert judgement was fair for the PhVC team (weighted kappa [Kw] 0.33)
and moderate for the pharmaceutical company team (Kw 0.41). For the updated
method, agreement was better for both the PhVC (Kw 0.58) and the pharmaceutical
company (Kw 0.52) teams. The inter- and intra-rater reproducibility of the
updated method based on the intrinsic imputability was satisfactory overall (Kw
0.30-0.91). Discrepancies between evaluations from PhVC and pharmaceutical
companies were observed with the updated method. CONCLUSION: The updated method
performed better than the current one for drug causality assessment, suggesting
that it should be used in routine pharmacovigilance.
PMID- 26423145
TI - Clinico-laboratory spectrum of dengue viral infection and risk factors associated
with dengue hemorrhagic fever: a retrospective study.
AB - BACKGROUND: The incidence of dengue is rising steadily in Malaysia since the
first major outbreak in 1973. Despite aggressive measures taken by the relevant
authorities, Malaysia is still facing worsening dengue crisis over the past few
years. There is an urgent need to evaluate dengue cases for better understanding
of clinic-laboratory spectrum in order to combat this disease. METHODS: A
retrospective analysis of dengue patients admitted to a tertiary care teaching
hospital during the period of six years (2008 - 2013) was performed. Patient's
demographics, clinical and laboratory findings were recorded via structured data
collection form. Patients were categorized into dengue fever (DF) and dengue
hemorrhagic fever (DHF). Appropriate statistical methods were used to compare
these two groups in order to determine difference in clinico-laboratory
characteristics and to identify independent risk factors of DHF. RESULTS: A total
667 dengue patients (30.69 +/- 16.13 years; Male: 56.7 %) were reviewed. Typical
manifestations of dengue like fever, myalgia, arthralgia, headache, vomiting,
abdominal pain and skin rash were observed in more than 40 % patients. DHF was
observed in 79 (11.8 %) cases. Skin rash, dehydration, shortness of breath,
pleural effusion and thick gall bladder were more significantly (P < 0.05)
associated with DHF than DF. Multivariate regression analysis demonstrated
presence of age > 40 years (OR: 4.1, P < 0.001), secondary infection (OR: 2.7, P
= 0.042), diabetes mellitus (OR: 2.8, P = 0.041), lethargy (OR: 3.1, P = 0.005),
thick gallbladder (OR: 1.7, P = 0.029) and delayed hospitalization (OR: 2.3, P =
0.037) as independent predictors of DHF. Overall mortality was 1.2 % in our
study. CONCLUSIONS: Current study demonstrated that DF and DHF present
significantly different clinico-laboratory profile. Older age, secondary
infection, diabetes mellitus, lethargy, thick gallbladder and delayed
hospitalization significantly predict DHF. Prior knowledge of expected clinical
profile and predictors of DHF/DSS development would provide information to
identify individuals at higher risk and on the other hand, give sufficient time
to clinicians for reducing dengue related morbidity and mortality.
PMID- 26423146
TI - Genome expansion in bacteria: the curios case of Chlamydia trachomatis.
AB - BACKGROUND: Recent findings indicated that a correlation between genomic % AT and
genome size within strains of microbial species was predominantly associated with
the uptake of foreign DNA. One species however, Chlamydia trachomatis, defied any
explanation. In the present study 79 fully sequenced C. trachomatis genomes,
representing ocular- (nine strains), urogenital- (36 strains) and lymphogranuloma
venereum strains (LGV, 22 strains), in three pathogroups, in addition to 12
laboratory isolates, were scrutinized with the intent of elucidating the positive
correlation between genomic AT content and genome size. RESULTS: The average size
difference between the strains of each pathogroup was largely explained by the
incorporation of genetic fragments. These fragments were slightly more AT rich
than their corresponding host genomes, but not enough to justify the difference
in AT content between the strains of the smaller genomes lacking the fragments.
In addition, a genetic region predominantly found in the ocular strains, which
had the largest genomes, was on average more GC rich than the host genomes of the
urogenital strains (58.64% AT vs. 58.69% AT), which had the second largest
genomes, implying that the foreign genetic regions cannot alone explain the
association between genome size and AT content in C. trachomatis. 23,492 SNPs
were identified for all 79 genomes, and although the SNPs were on average
slightly GC rich (~47% AT), a significant association was found between genome
wide SNP AT content, for each pathogroup, and genome size (p < 0.001, R (2) =
0.86) in the C. trachomatis strains. CONCLUSIONS: The correlation between genome
size and AT content, with respect to the C. trachomatis pathogroups, was
explained by the incorporation of genetic fragments unique to the ocular and/or
urogenital strains into the LGV- and urogential strains in addition to the genome
wide SNP AT content differences between the three pathogroups.
PMID- 26423147
TI - Integrating vector control across diseases.
AB - BACKGROUND: Vector-borne diseases cause a significant proportion of the overall
burden of disease across the globe, accounting for over 10 % of the burden of
infectious diseases. Despite the availability of effective interventions for many
of these diseases, a lack of resources prevents their effective control. Many
existing vector control interventions are known to be effective against multiple
diseases, so combining vector control programmes to simultaneously tackle several
diseases could offer more cost-effective and therefore sustainable disease
reductions. DISCUSSION: The highly successful cross-disease integration of
vaccine and mass drug administration programmes in low-resource settings acts a
precedent for cross-disease vector control. Whilst deliberate implementation of
vector control programmes across multiple diseases has yet to be trialled on a
large scale, a number of examples of 'accidental' cross-disease vector control
suggest the potential of such an approach. Combining contemporary high-resolution
global maps of the major vector-borne pathogens enables us to quantify overlap in
their distributions and to estimate the populations jointly at risk of multiple
diseases. Such an analysis shows that over 80 % of the global population live in
regions of the world at risk from one vector-borne disease, and more than half
the world's population live in areas where at least two different vector-borne
diseases pose a threat to health. Combining information on co-endemicity with an
assessment of the overlap of vector control methods effective against these
diseases allows us to highlight opportunities for such integration. Malaria,
leishmaniasis, lymphatic filariasis, and dengue are prime candidates for combined
vector control. All four of these diseases overlap considerably in their
distributions and there is a growing body of evidence for the effectiveness of
insecticide-treated nets, screens, and curtains for controlling all of their
vectors. The real-world effectiveness of cross-disease vector control programmes
can only be evaluated by large-scale trials, but there is clear evidence of the
potential of such an approach to enable greater overall health benefit using the
limited funds available.
PMID- 26423148
TI - Antigen Specificity of Type I NKT Cells Is Governed by TCR beta-Chain Diversity.
AB - NKT cells recognize lipid-based Ags presented by CD1d. Type I NKT cells are often
referred to as invariant owing to their mostly invariant TCR alpha-chain usage
(Valpha14-Jalpha18 in mice, Valpha24-Jalpha18 in humans). However, these cells
have diverse TCR beta-chains, including Vbeta8, Vbeta7, and Vbeta2 in mice and
Vbeta11 in humans, joined to a range of TCR Dbeta and Jbeta genes. In this study,
we demonstrate that TCR beta-chain composition can dramatically influence lipid
Ag recognition in an Ag-dependent manner. Namely, the glycolipids alpha
glucosylceramide and isoglobotrihexosylceramide were preferentially recognized by
Vbeta7(+) NKT cells from mice, whereas the alpha-galactosylceramide analog OCH,
with a truncated sphingosine chain, was preferentially recognized by Vbeta8(+)
NKT cells from mice. We show that the influence of the TCR beta-chain is due to a
combination of Vbeta-, Jbeta-, and CDR3beta-encoded residues and that these TCRs
can recapitulate the selective Ag reactivity in TCR-transduced cell lines.
Similar observations were made with human NKT cells where different CDR3beta
encoded residues determined Ag preference. These findings indicate that NKT TCR
beta-chain diversity results in differential and nonhierarchical Ag recognition
by these cells, which implies that some Ags can preferentially activate type I
NKT cell subsets.
PMID- 26423150
TI - Immunosuppression and Aberrant T Cell Development in the Absence of N
Myristoylation.
AB - N-myristoylation refers to the attachment of myristic acid to the N-terminal
glycine of proteins and substantially affects their intracellular targeting and
functions. The thymus represents an organ with a prominent N-myristoylation
activity. To elucidate the role of protein N-myristoylation for thymocyte
development, we generated mice with a T cell lineage-specific deficiency in N
myristoyl transferase (Nmt)1 and 2. Depletion of Nmt activity in T cells led to a
defective transmission of TCR signals, a developmental blockage of thymocytes at
the transition from double-negative 3 to 4 stages, and a reduction of all the
following stages. We could demonstrate that Lck and myristoylated alanine-rich C
kinase substrate, two main myristoylated kinases in T cells, were mislocalized in
the absence of Nmt activity. N-myristoylation was also indispensable for early
and distal TCR signaling events such as CD3zeta, Zap70, and Erk activation and
for release of cytokines such as IFN-gamma and IL-2. As a consequence, the
initiation and propagation of the TCR signaling cascade was severely impaired.
Furthermore, we showed that the absence of myristoylation had an
immunosuppressive effect on T cells in vivo after treatment with CpG and
stimulation of the TCR with the staphylococcal enterotoxin B superantigen.
Therefore, protein myristoylation is indispensable in T cell development and
activation and its inhibition might offer a novel strategy to achieve
immunosuppression.
PMID- 26423149
TI - SARM1, Not MyD88, Mediates TLR7/TLR9-Induced Apoptosis in Neurons.
AB - Neuronal apoptosis is a key aspect of many different neurologic diseases, but the
mechanisms remain unresolved. Recent studies have suggested a mechanism of innate
immune-induced neuronal apoptosis through the stimulation of endosomal TLRs in
neurons. TLRs are stimulated both by pathogen-associated molecular patterns as
well as by damage-associated molecular patterns, including microRNAs released by
damaged neurons. In the present study, we identified the mechanism responsible
for TLR7/TLR9-mediated neuronal apoptosis. TLR-induced apoptosis required
endosomal localization of TLRs but was independent of MyD88 signaling. Instead,
apoptosis required the TLR adaptor molecule SARM1, which localized to the
mitochondria following TLR activation and was associated with mitochondrial
accumulation in neurites. Deficiency in SARM1 inhibited both mitochondrial
accumulation in neurites and TLR-induced apoptosis. These studies identify a non
MyD88 pathway of TLR7/ TLR9 signaling in neurons and provide a mechanism for how
innate immune responses in the CNS directly induce neuronal damage.
PMID- 26423152
TI - Authentic GITR Signaling Fails To Induce Tumor Regression unless Foxp3+
Regulatory T Cells Are Depleted.
AB - The glucocorticoid-induced TNFR family-related protein (GITR, TNFRSF18, CD357) is
expressed on effector and regulatory T (Treg) cells. Previous studies
demonstrated that GITR triggering by anti-GITR mAb enhanced T and B cell-mediated
immune responses. GITR-deficient T cells, however, also proliferate more than
normal T cells, and this effect is unexplained. Because the activities of mAbs
are controlled by their Fc regions, the true effect of GITR signaling needs to be
determined by examining its interaction with authentic ligand. Therefore, we
generated a pentamerized form of the GITRL extracellular domain (pGITRL) for
ligation to GITR and compared its effect on T cells with that of anti-GITR mAb.
The pGITRL was more effective than anti-GITR mAb in enhancing the proliferation
of effector and regulatory cells in vitro and in vivo. Nonetheless, the growth of
MC38 adenocarcinoma cells in vivo was only suppressed for initial 15 d by pGITRL,
whereas it was suppressed indefinitely by anti-GITR mAb. Detailed analysis
revealed that pGITRL induced extensive proliferation of Foxp3(+)CD4(+) Treg cells
and led to the accumulation of activated Treg cells in tumor tissue and draining
lymph nodes. Because GITR signaling could not neutralize the suppressive activity
of activated Treg cells, pGITRL seems to lose its adjuvant effect when sufficient
activated Treg cells have accumulated in the lymph nodes and tumor tissue.
Indeed, the antitumor effects of pGITRL were markedly enhanced by depleting
CD4(+) cells. These results suggest that GITR signaling has stimulatory effects
on effector T cells and inhibitory effects through Treg cells.
PMID- 26423151
TI - IL-25 or IL-17E Protects against High-Fat Diet-Induced Hepatic Steatosis in Mice
Dependent upon IL-13 Activation of STAT6.
AB - IL-25 or IL-17E is a member of IL-17 cytokine family and has immune-modulating
activities. The role of IL-25 in maintaining lipid metabolic homeostasis remains
unknown. We investigated the effects of exogenous IL-25 or deficiency of IL-25 on
hepatic lipid accumulation. IL-25 expression was examined in paraffin-embedded
tissue sections of liver from patients or in the livers from mice. Mouse model of
steatosis was induced by feeding a high-fat diet (HFD). Extent of steatosis as
well as expression of cytokines, key enzymes for lipid metabolic pathways,
markers for Kupffer cells/macrophages, and lipid droplet (LD) proteins, were
analyzed. Our results show that hepatic steatosis in mice was accompanied by
increased LD proteins, but decreased IL-25 in the liver. Decreased hepatic IL-25
was also observed in patients with fatty liver. Administration of IL-25 to HFD
fed wild-type mice led to a significant improvement in hepatic steatosis. This
effect was associated with increased expression of IL-13, development of
alternatively activated Kupffer cells/macrophages, and decreased expression of LD
proteins in the liver. In contrast, administration of IL-25 to HFD-fed mice
deficient in STAT6 or IL-13 had no effects. In addition, stimulation of primary
hepatocytes with IL-13, but not IL-25, resulted in downregulation of LD proteins.
Finally, mice deficient in IL-25 had exacerbated hepatic lipid accumulation when
fed the HFD. These data demonstrate that dysregulated IL-25 expression
contributes to lipid accumulation, whereas exogenous IL-25 protects against
hepatic steatosis through IL-13 activation of STAT6. IL-25 and IL-13 are
potential therapeutic agents for hepatic steatosis and associated pathologies.
PMID- 26423153
TI - Adaptor Protein-3-Mediated Trafficking of TLR2 Ligands Controls Specificity of
Inflammatory Responses but Not Adaptor Complex Assembly.
AB - Innate immune engagement results in the activation of host defenses that produce
microbe-specific inflammatory responses. A long-standing interest in the field of
innate immunity is to understand how varied host responses are generated through
the signaling of just a limited number of receptors. Recently, intracellular
trafficking and compartmental partitioning have been identified as mechanisms
that provide signaling specificity for receptors by regulating signaling platform
assembly. We show that cytokine activation as a result of TLR2 stimulation occurs
at different intracellular locations and is mediated by the phagosomal
trafficking molecule adaptor protein-3 (AP-3). AP-3 is required for trafficking
TLR2 purified ligands or the Lyme disease causing bacterium, Borrelia
burgdorferi, to LAMP-1 lysosomal compartments. The presence of AP-3 is necessary
for the activation of cytokines such as IL-6 but not TNF-alpha or type I IFNs,
suggesting induction of these cytokines occurs from a different compartment. Lack
of AP-3 does not interfere with the recruitment of TLR signaling adaptors TRAM
and MyD88 to the phagosome, indicating that the TLR-MyD88 signaling complex is
assembled at a prelysosomal stage and that IL-6 activation depends on proper
localization of signaling molecules downstream of MyD88. Finally, infection of AP
3-deficient mice with B. burgdorferi resulted in altered joint inflammation
during murine Lyme arthritis. Our studies further elucidate the effects of
phagosomal trafficking on tailoring immune responses in vitro and in vivo.
PMID- 26423155
TI - Editorial: Engineered Magnetic Core@Shell Structures.
PMID- 26423154
TI - Effect of sex and fatigue on single leg squat kinematics in healthy young adults.
AB - BACKGROUND: The single-leg squat (SLS) test is widely used in screening for
musculoskeletal injury risk. Little is known, however, of lower limb, pelvis, and
trunk kinematics of SLS performance or the effect of sex and fatigue. Our aim was
to determine sex differences and the influence of fatigue on SLS kinematics in
healthy young adults. METHODS: We recruited 60 healthy men and women between the
ages of 20 and 40 years. Three-dimensional kinematic data was collected for SLSs
with a ten-camera VICON motion analysis system (Oxford Metrics, UK) before and
after a lower limb fatiguing exercise regime. One-way ANCOVA was used to make sex
comparisons of kinematic parameters and repeated measures ANOVA was used to
determine the effect of fatigue and the interaction with sex. RESULTS: 30 men
(25.6 +/- 4.8 years) and 30 women (25.1 +/- 3.8 years) volunteered to
participate. Peak pelvic rotation (3.9 +/- 4.1 vs. 7.7 +/- 6.2 deg, P = 0.03),
peak hip internal rotation (-1.8 +/- 5.7 vs. 3.0 +/- 7.3 deg, P = 0.02), hip
adduction range (11.7 +/- 4.8 vs. 18.3 +/- 6.7 deg, P = 0.004), and hip rotation
range (10.7 +/- 3.9 vs. 13.0 +/- 4.2 deg, P = 0.04) were smaller for men than for
women. Likewise, distance of mediolateral knee motion (180 +/- 51 vs. 227 +/- 50
mm, P = 0.001) was shorter for men than for women. The kinematic response to
fatigue was an increase in trunk flexion, lateral flexion and rotation, an
increase in pelvic tilt, obliquity and rotation, and an increase in hip flexion
and adduction range (P <=0.05). CONCLUSIONS: Sex differences in SLS kinematics
appear to apply only at the hip, knee, and pelvis and not at the trunk. Fatiguing
exercise, however, produces changes at the trunk and pelvis with little effect on
the knee.
PMID- 26423157
TI - 71st Congress of the Italian Society of Pediatrics.
PMID- 26423156
TI - CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac
specification, differentiation and homeostasis.
AB - Long noncoding RNAs (lncRNAs) are emerging as important regulators of
developmental pathways. However, their roles in human cardiac precursor cell
(CPC) remain unexplored. To characterize the long noncoding transcriptome during
human CPC cardiac differentiation, we profiled the lncRNA transcriptome in CPCs
isolated from the human fetal heart and identified 570 lncRNAs that were
modulated during cardiac differentiation. Many of these were associated with
active cardiac enhancer and super enhancers (SE) with their expression being
correlated with proximal cardiac genes. One of the most upregulated lncRNAs was a
SE-associated lncRNA that was named CARMEN, (CAR)diac (M)esoderm (E)nhancer
associated (N)oncoding RNA. CARMEN exhibits RNA-dependent enhancing activity and
is upstream of the cardiac mesoderm-specifying gene regulatory network.
Interestingly, CARMEN interacts with SUZ12 and EZH2, two components of the
polycomb repressive complex 2 (PRC2). We demonstrate that CARMEN knockdown
inhibits cardiac specification and differentiation in cardiac precursor cells
independently of MIR-143 and -145 expression, two microRNAs located proximal to
the enhancer sequences. Importantly, CARMEN expression was activated during
pathological remodeling in the mouse and human hearts, and was necessary for
maintaining cardiac identity in differentiated cardiomyocytes. This study
demonstrates therefore that CARMEN is a crucial regulator of cardiac cell
differentiation and homeostasis.
PMID- 26423159
TI - What Can We Do About Stigma?
PMID- 26423158
TI - Can preoperative 3-T MRI predict nipple-areolar complex involvement in patients
with breast cancer?
AB - PURPOSE: To evaluate the diagnostic performances of preoperative 3-T breast MRI
for predicting nipple-areolar complex (NAC) involvement. MATERIALS AND METHODS:
We analyzed the predictors of NAC involvement in breast cancer, with diagnostic
performances. RESULTS: Among the 403 patients, 43 cases were surgically confirmed
for NAC involvement. For predicting NAC involvement, sensitivity, specificity,
positive predictive value, negative predictive value, and accuracy were 60.5%,
87.5%, 36.6%, 94.9%, and 84.6%, respectively. Continuity to NAC, unilateral
enhancement of NAC and thickening of NAC were significant magnetic resonance
findings predictive of NAC involvement. CONCLUSIONS: Preoperative 3-T breast MRI
is a useful method to predict NAC involvement in breast cancer patients.
PMID- 26423161
TI - Can the Americans With Disabilities Act Reduce the Death Toll From Police
Encounters With Persons With Mental Illness?
AB - A substantial proportion of people shot by police have mental disorders, and many
of these killings appear to have been avoidable. One tool to encourage better
police training and more cautious behavior is the Americans with Disabilities Act
(ADA). However, police groups oppose application of the ADA to arrests, fearing
limits on their discretion, and the U.S. Supreme Court appears to favor that
view. When the Court declined a recent opportunity to decide the question, it
left open a window of opportunity during which the ADA can be leveraged to
improve how police officers deal with persons with mental illness.
PMID- 26423162
TI - Back From the Blue and the Black.
PMID- 26423163
TI - Preventing First Hospitalization for Psychosis: In Reply.
PMID- 26423164
TI - Preventing First Hospitalization for Psychosis.
PMID- 26423165
TI - Suicide Prevention in Patient and Nonpatient Populations.
PMID- 26423166
TI - Suicide Prevention in Patient and Nonpatient Populations: In Reply.
PMID- 26423167
TI - Were Concerns With Misidentification in Special Education Overlooked? In Reply.
PMID- 26423168
TI - Were Concerns With Misidentification in Special Education Overlooked?
PMID- 26423171
TI - Gold Award: Improving Community Safety by Providing Treatment to a Highly
Marginalized Clinical Population. Sexual Behaviours Clinic, Integrated Forensic
Program, Royal Ottawa Mental Health Centre, Ottawa, Ontario, Canada.
PMID- 26423172
TI - Bronze Award: A Private-Public Partnership to Deliver Population-Level Integrated
Care to Low-Income Seniors in Pennsylvania. SUSTAIN (SUpporting Seniors receiving
Treatment And INtervention), Department of Psychiatry, Perelman School of
Medicine at the University of Pennsylvania, Philadelphia, and the Department of
Aging, Commonwealth of Pennsylvania, Harrisburg.
PMID- 26423173
TI - Gold Award: Community-Based Program: A Health Care Home for the "Whole Person" in
Missouri's Community Mental Health Centers. Missouri Community Mental Health
Center Health Home Program, Jefferson City, Missouri.
PMID- 26423174
TI - Silver Award: Student Outreach and Teacher Training to Ensure Prevention, Early
Recognition, and Treatment of Mental Health Problems. Mental Health 101 and
Typical or Troubled?, Mental Health Association of East Tennessee, Knoxville.
PMID- 26423175
TI - Tadalafil-loaded nanostructured lipid carriers using permeation enhancers.
AB - Tadalafil is a phosphodiesterase-5 inhibitor indicated for the treatment of
erectile dysfunction. In this study, we prepared and evaluated transdermal
nanostructured lipid carriers (NLC) to improve the skin permeability of
tadalafil. Tadalafil-loaded NLC dispersions were prepared using glyceryl
monostearate as a solid lipid, oleic acid as a liquid lipid, and Tween 80 as a
surfactant. We characterized the dispersions according to particle size,
polydispersity index, zeta potential, encapsulation efficiency, and transmission
electron microscopy. In vitro skin permeation studies were carried out using
Franz diffusion cells, and cytotoxicity was examined using HaCaT keratinocyte
cell lines. Tadalafil skin permeability increased for all tadalafil-loaded NLC
formulations. The tadalafil-loaded NLC dispersion with ethanol and limonene as
skin permeation enhancers exhibited the highest flux (~4.8-fold) compared to that
observed with tadalafil solution alone. Furthermore, a tadalafil-loaded NLC gel
with selected permeation enhancers showed tolerance against toxicity in HaCaT
cells. These results suggest that the NLC formulations with ethanol and limonene
as skin permeation enhancers could be a promising dermal delivery carrier for
tadalafil.
PMID- 26423176
TI - Use of similarity scoring in the development of oral solid dosage forms.
AB - In the oral solid dosage form space, material physical properties have a strong
impact on the behaviour of the formulation during processing. The ability to
identify materials with similar characteristics (and thus expected to exhibit
similar behaviour) within the company's portfolio can help accelerate drug
development by enabling early assessment and prediction of potential challenges
associated with the powder properties of a new active pharmaceutical ingredient.
Such developments will aid the production of robust dosage forms, in an efficient
manner. Similarity scoring metrics are widely used in a number of scientific
fields. This study proposes a practical implementation of this methodology within
pharmaceutical development. The developed similarity metrics is based on the
Mahalanobis distance. Scanning electron microscopy was used to confirm
morphological similarity between the reference material and the closest matches
identified by the metrics proposed. The results show that the metrics proposed
are able to successfully identify material with similar physical properties.
PMID- 26423177
TI - Ocular safety comparison of non-steroidal anti-inflammatory eye drops used in
pseudophakic cystoid macular edema prevention.
AB - Non-steroidal anti-inflammatory drug (NSAID) eye drops are widely used to treat
ocular inflammatory conditions related to ophthalmic surgical procedures, such as
pseudophakic cystoid macular edema, and they have been used for off-label
treatments. The most commonly used NSAIDs are diclofenac and ketorolac and the
new molecules bromfenac and nepafenac have also been used. We used primary human
keratocytes in cell culture in combination with a novel technology that evaluates
dynamic real-time cytotoxicity through impedance analysis. This study also
included classic cell viability tests (WST-1((r)) and AlamarBlue((r))), wound
healing assay, Hen's Egg Test and an ex vivo histopathological assay. NSAIDs were
shown to have important cytotoxicities and to retard the healing response.
Furthermore, the new eye drops containing bromfenac and nepafenac were more
cytotoxic than the more classical eye drops. Nevertheless, no immuno
histochemical changes or acute irritation processes were observed after the
administration of any eye drops tested. Due to cytotoxicity and the total absence
of discomfort and observable injuries after the administration of these drugs,
significant corneal alterations, such as corneal melts, can develop without any
previous warning signs of toxicity.
PMID- 26423178
TI - Interferon-stimulated gene (ISG) 60, as well as ISG56 and ISG54, positively
regulates TLR3/IFN-beta/STAT1 axis in U373MG human astrocytoma cells.
AB - Treatment of cells with interferons (IFNs) induces the phosphorylation of signal
transducer and activator of transcription 1 (STAT1), leading to the expression of
hundreds of IFN-stimulated genes (ISGs). ISGs exert various antiviral and pro
inflammatory reactions. We have previously reported that ISG56 and ISG54 are
induced by polyinosinic-polycytidylic acid (poly IC), an authentic agonist for
Toll-like receptor 3 (TLR3), in U373MG human astrocytoma cells. ISG56 and ISG54
are also named as IFN-induced proteins with tetratricopeptide repeats (IFIT) 1
and IFIT2, respectively. In the present study, we demonstrated that poly IC
induces the expression of ISG60, also named as IFIT3, in U373MG cells. RNA
interference experiments showed that the induction of ISG60 by poly IC was
mediated by TLR3, IFN-beta, ISG56 and ISG54, whereas ISG60 is involved in poly IC
induced expression of ISG56, ISG54 and a chemokine CXCL10. The level of
phosphorylated STAT1 was enhanced by poly IC, and it was inhibited by knockdown
of ISG56, ISG54 or ISG60. These results suggest that there is a positive feedback
loop between phosphorylated STAT1 and these ISGs.
PMID- 26423179
TI - Management of late-life depression: a major leap forward.
PMID- 26423180
TI - Increasing value and reducing waste in biomedical research: who's listening?
AB - The biomedical research complex has been estimated to consume almost a quarter of
a trillion US dollars every year. Unfortunately, evidence suggests that a high
proportion of this sum is avoidably wasted. In 2014, The Lancet published a
series of five reviews showing how dividends from the investment in research
might be increased from the relevance and priorities of the questions being
asked, to how the research is designed, conducted, and reported. 17
recommendations were addressed to five main stakeholders-funders, regulators,
journals, academic institutions, and researchers. This Review provides some
initial observations on the possible effects of the Series, which seems to have
provoked several important discussions and is on the agendas of several key
players. Some examples of individual initiatives show ways to reduce waste and
increase value in biomedical research. This momentum will probably move strongly
across stakeholder groups, if collaborative relationships evolve between key
players; further important work is needed to increase research value. A
forthcoming meeting in Edinburgh, UK, will provide an initial forum within which
to foster the collaboration needed.
PMID- 26423181
TI - Acute-on-chronic liver failure.
AB - Acute-on-chronic liver failure combines an acute deterioration in liver function
in an individual with pre-existing chronic liver disease and hepatic and
extrahepatic organ failures, and is associated with substantial short-term
mortality. Common precipitants include bacterial and viral infections, alcoholic
hepatitis, and surgery, but in more than 40% of patients, no precipitating event
is identified. Systemic inflammation and susceptibility to infection are
characteristic pathophysiological features. A new diagnostic score, the Chronic
Liver Failure Consortium (CLIF-C) organ failure score, has been developed for
classification and prognostic assessment of patients with acute-on-chronic liver
failure. Disease can be reversed in many patients, and thus clinical management
focuses upon the identification and treatment of the precipitant while providing
multiorgan-supportive care that addresses the complex pattern of physiological
disturbance in critically ill patients with liver disease. Liver transplantation
is a highly effective intervention in some specific cases, but recipient
identification, organ availability, timing of transplantation, and high resource
use are barriers to more widespread application. Recognition of acute-on-chronic
liver failure as a clinically and pathophysiologically distinct syndrome with
defined diagnostic and prognostic criteria will help to encourage the development
of new management pathways and interventions to address the unacceptably high
mortality.
PMID- 26423183
TI - Logistic Regression Analysis of Contrast-Enhanced Ultrasound and Conventional
Ultrasound Characteristics of Sub-centimeter Thyroid Nodules.
AB - The purpose of the study described here was to determine specific characteristics
of thyroid microcarcinoma (TMC) and explore the value of contrast-enhanced
ultrasound (CEUS) combined with conventional ultrasound (US) in the diagnosis of
TMC. Characteristics of 63 patients with TMC and 39 with benign sub-centimeter
thyroid nodules were retrospectively analyzed. Multivariate logistic regression
analysis was performed to determine independent risk factors. Four variables were
included in the logistic regression models: age, shape, blood flow distribution
and enhancement pattern. The area under the receiver operating characteristic
curve was 0.919. With 0.113 selected as the cutoff value, sensitivity,
specificity, positive predictive value, negative predictive value and accuracy
were 90.5%, 82.1%, 89.1%, 84.2% and 87.3%, respectively. Independent risk factors
for TMC determined with the combination of CEUS and conventional US were age,
shape, blood flow distribution and enhancement pattern. Age was negatively
correlated with malignancy, whereas shape, blood flow distribution and
enhancement pattern were positively correlated. The logistic regression model
involving CEUS and conventional US was found to be effective in the diagnosis of
sub-centimeter thyroid nodules.
PMID- 26423182
TI - Efficacy, safety, and tolerability of augmentation pharmacotherapy with
aripiprazole for treatment-resistant depression in late life: a randomised,
double-blind, placebo-controlled trial.
AB - BACKGROUND: Treatment-resistant major depression is common and potentially life
threatening in elderly people, in whom little is known about the benefits and
risks of augmentation pharmacotherapy. We aimed to assess whether aripiprazole is
associated with a higher probability of remission than is placebo. METHODS: We
did a randomised, double-blind, placebo-controlled trial at three centres in the
USA and Canada to test the efficacy and safety of aripiprazole augmentation for
adults aged older than 60 years with treatment-resistant depression (Montgomery
Asberg Depression Rating Scale [MADRS] score of >=15). Patients who did not
achieve remission during a pre-trial with venlafaxine extended-release (150-300
mg/day) were randomly assigned (1:1) to the addition of aripiprazole (target dose
10 mg [maximum 15 mg] daily) daily or placebo for 12 weeks. The computer
generated randomisation was done in blocks and stratified by site. Only the
database administrator and research pharmacists had knowledge of treatment
assignment. The primary endpoint was remission, defined as an MADRS score of 10
or less (and at least 2 points below the score at the start of the randomised
phase) at both of the final two consecutive visits, analysed by intention to
treat. This trial is registered with ClinicalTrials.gov, number NCT00892047.
FINDINGS: From July 20, 2009, to Dec 30, 2013, we recruited 468 eligible
participants, 181 (39%) of whom did not remit and were randomly assigned to
aripiprazole (n=91) or placebo (n=90). A greater proportion of participants in
the aripiprazole group achieved remission than did those in the placebo group (40
[44%] vs 26 [29%] participants; odds ratio [OR] 2.0 [95% CI 1.1-3.7], p=0.03;
number needed to treat [NNT] 6.6 [95% CI 3.5-81.8]). Akathisia was the most
common adverse effect of aripiprazole (reported in 24 [26%] of 91 participants on
aripiprazole vs 11 [12%] of 90 on placebo). Compared with placebo, aripiprazole
was also associated with more Parkinsonism (15 [17%] of 86 vs two [2%] of 81
participants), but not with treatment-emergent suicidal ideation (13 [21%] of 61
vs 19 [29%] of 65 participants) or other measured safety variables.
INTERPRETATION: In adults aged 60 years or older who do not achieve remission
from depression with a first-line antidepressant, the addition of aripiprazole is
effective in achieving and sustaining remission. Tolerability concerns include
the potential for akathisia and Parkinsonism. FUNDING: National Institute of
Mental Health, UPMC Endowment in Geriatric Psychiatry, Taylor Family Institute
for Innovative Psychiatric Research, National Center for Advancing Translational
Sciences, and the Campbell Family Mental Health Research Institute.
PMID- 26423184
TI - Lixisenatide clinical experience on patients with type 2 diabetes and obesity in
endocrinology offices in Malaga.
PMID- 26423185
TI - Transcatheter pulmonary valve replacement: State of the art.
AB - BACKGROUND: The number of patients undergoing transcatheter pulmonary valve
replacement has been steadily increasing, resulting in many research projects
focusing on this patient population. This has highlighted the need to summarize
the currently available data. METHODS: A review of the literature was conducted
and the results summarized. RESULTS: At present, the two commercially available
valves approved for transcatheter pulmonary valve replacement include the Edwards
Sapien valve and the Medtronic Melody valve. More data has been published
relating to the Melody valve; this included the incidence of coronary anatomy
prohibiting valve implantation of 5%, an incidence of conduit disruption of 6%,
and freedom from stent fracture of the Melody valve stent of 60% at 30 months.
Short and medium term outcomes seem to be comparable if not superior to surgical
valve replacement, but long-term data is still lacking. There may also be a cost
benefit with transcatheter valve implantation when compared to surgical pulmonary
valve replacement. CONCLUSIONS: Transcatheter pulmonary valve replacement is here
to stay. The main challenge of treating patients with a native right ventricular
outflow tract still needs to be addressed and device development efforts centered
in this area. (c) 2015 Wiley Periodicals, Inc.
PMID- 26423186
TI - Making the most of a new HIV self-test.
PMID- 26423187
TI - HIV testing in primary care.
PMID- 26423188
TI - HIV eradication: is cord blood the answer?
PMID- 26423189
TI - ART and prevention of HIV-associated tuberculosis.
PMID- 26423190
TI - Behaviour, not mobility, is a risk factor for HIV.
PMID- 26423191
TI - The need for standardisation of the HIV continuum of care.
PMID- 26423192
TI - Co-trimoxazole in people on antiretroviral therapy for HIV.
PMID- 26423193
TI - Co-trimoxazole in people on antiretroviral therapy for HIV--authors' reply.
PMID- 26423194
TI - The FACTS about women and pre-exposure prophylaxis.
PMID- 26423195
TI - Promotion of rapid testing for HIV in primary care (RHIVA2): a cluster-randomised
controlled trial.
AB - BACKGROUND: Many people with HIV are undiagnosed. Early diagnosis saves lives and
reduces onward transmission. We assessed whether an education programme promoting
rapid HIV testing in general practice would lead to increased and earlier HIV
diagnosis. METHODS: In this cluster randomised controlled trial in Hackney
(London, UK), general practices were randomly assigned (1:1) to offer either opt
out rapid HIV testing to newly registering adults or continue usual care. All
practices were invited to take part. Practices were randomised by an independent
clinical trials unit statistician with a minimisation program, maintaining
allocation concealment. Neither patients nor investigators were masked to
treatment allocation. The primary outcome was CD4 count at diagnosis. Secondary
outcomes were rate of diagnosis, proportion with CD4 count less than 350 cells
per MUL, and proportion with CD4 count less than 200 cells per MUL. This study is
registered with ClinicalTrials.gov, number ISRCTN63473710. FINDINGS: 40 of 45
(89%) general practices agreed to participate: 20 were assigned to the
intervention group (44 971 newly registered adult patients) and 20 to the control
group (38 464 newly registered adult patients), between April 19, 2010, and Aug
31, 2012. Intervention practices diagnosed 32 people with HIV versus 14 in
control practices. Mean CD4 count at diagnosis was 356 cells per MUL (SD 254)
intervention practices versus 270 (SD 257) in control practices (adjusted
difference of square root CD4 count 3.1, 95% CI -1.2 to 7.4; p=0.16);); in a pre
planned sensitivity analysis excluding patients diagnosed via antenatal care, the
difference was 6.4 (95% CI, 1.2 to 11.6; p=0.017). Rate of HIV diagnosis was 0.30
(95% CI 0.11 to 0.85) per 10 000 patients per year in intervention practices
versus 0.07 (0.02 to 0.20) in control practices (adjusted ratio of geometric
means 4.51, 95% CI 1.27 to 16.05; p=0.021). 55% of patients in intervention
practices versus 73% in control practices had CD4 count less than 350 cells per
MUL (risk ratio 0.75, 95% CI 0.53 to 1.07). 28% versus 46% had CD4 count less
than 200 cells per MUL (0.60, 0.32 to 1.13). All patients diagnosed by rapid
testing were successfully transferred into specialist care. No adverse events
occurred. INTERPRETATION: Promotion of opt-out rapid testing in general practice
led to increased rate of diagnosis, and might increase early detection, of HIV.
We therefore recommend implementation of HIV screening in general practices in
areas with high HIV prevalence. FUNDING: UK Department of Health, NHS City and
Hackney.
PMID- 26423196
TI - CCR5 Delta32 homozygous cord blood allogeneic transplantation in a patient with
HIV: a case report.
AB - BACKGROUND: Allogeneic donor CCR5 Delta32 homozygous haemopoietic cell
transplantation (HCT) provides the only evidence to date of long-term control of
HIV infection. However, availability of conventional CCR5 Delta32 homozygous
donors is insufficient to develop this as a therapeutic strategy further.
METHODS: We present a 37-year-old patient with HIV-1 infection and aggressive
lymphoma who had disease progression after five lines of radiochemotherapy
including an autologous HCT, and in the absence of matched sibling donors,
received an allogeneic HCT with four of six HLA-matched CCR5 Delta32 homozygous
cord blood cells (StemCyte, Covina, CA), supported with purified CD34+ cells from
a haploidentical sibling. Blood or tissue samples were obtained before and weekly
after HCT to monitor transplant and HIV infection, including chimerism analysis,
CCR5 genotyping and viral tropism, viral isolation and sequence, viral reservoir
analysis, immune activation and proliferation, and ex-vivo cell infectivity
assays. Combined antiretroviral therapy continued during the procedure. FINDINGS:
The patient's HIV was CCR5-tropic by genotypic and phenotypic analyses. Baseline
latent reservoir tests showed HIV DNA copies in bulk and resting CD4 T cells and
in gut-associated lymphoid tissue, CD4 T-cell-associated HIV RNA, replication
competent viral size of 2.1 copies per 10(7) CD4 T cells, and single copy assay
of 303 copies per mL. After HCT, plasma HIV DNA load was undetectable by
ultrasensitive analyses. Upon cord blood full chimerism, the patient's CCR5
Delta32 homozygous CD4 T cells responded to proliferation and activation stimuli
and became resistant to infection by the patient's viral isolate and by
laboratory-adapted HIV-1 strains. Death related to lymphoma progression
regretfully prevented long-term monitoring of the patient's viral reservoir.
INTERPRETATION: CCR5 Delta32 homozygous cord blood reconstitution can
successfully eliminate HIV-1 and render the allogeneic graft recipient's T
lymphocytes resistant to HIV infection. Thus, they build on the evidence
available to strongly support the use of cord blood as a strategic platform for a
broader application of non-functional CCR5 transplantation to other infected
individuals. FUNDING: Spanish Secretariat of Research, the American Foundation
for AIDS Research (amfAR).
PMID- 26423197
TI - Does antiretroviral therapy reduce HIV-associated tuberculosis incidence to
background rates? A national observational cohort study from England, Wales, and
Northern Ireland.
AB - BACKGROUND: Whether the incidence of tuberculosis in HIV-positive people
receiving long-term antiretroviral therapy (ART) remains above background
population rates is unclear. We compared tuberculosis incidence in people
receiving ART with background rates in England, Wales, and Northern Ireland.
METHODS: We analysed a national cohort of HIV-positive individuals linked to the
national tuberculosis register. Tuberculosis incidence in the HIV-positive cohort
(2007-11) was stratified by ethnic origin and time on ART and compared with
background rates (2009). Ethnic groups were defined as follows: the black African
group included all individuals of black African origin, including those born in
the UK and overseas; the white ethnic group included all white individuals born
in the UK and overseas; the south Asian group included those of Indian,
Pakistani, and Bangladeshi origin, born in the UK and overseas; and the other
ethnic group included all other ethnic origins, including black Afro-Caribbeans.
FINDINGS: The HIV-positive cohort comprised 79 919 individuals, in whom there
were 1550 incident cases in 231 664 person-years of observation (incidence 6.7
cases per 1000 person-years). Incidence of tuberculosis in the HIV-positive
cohort was 13.6 per 1000 person-years in black Africans and 1.7 per 1000 person
years in white individuals. Incidence of tuberculosis during long-term ART (>=5
years) in black Africans with HIV was 2.4 per 1000 person-years, similar to
background rates of 1.9 per 1000 person-years in this group (rate ratio 1.2, 95%
CI 0.96-1.6; p=0.083); but in white individuals with HIV on long-term ART the
incidence of 0.5 per 1000 person-years was higher than the background rate of
0.04 per 1000 person-years (rate ratio 14.5, 9.4-21.3; p<0.0001). The increased
incidence relative to background in white HIV-positive individuals persisted when
analysis was restricted to person-time accrued on ART with CD4 counts of at least
500 cells per MUL and when white HIV-positive individuals born abroad were
excluded. INTERPRETATION: Tuberculosis incidence is unacceptably high
irrespective of HIV status in black Africans. In white individuals with HIV,
tuberculosis incidence is significantly higher than background rates in white
people despite long-term ART. Expanded testing and treatment for latent
tuberculosis infection to all HIV-infected adults, irrespective of ART status and
CD4 cell count, might be warranted. FUNDING: Public Health England.
PMID- 26423198
TI - Evaluation of paper gradient concentration strips for antifungal combination
testing of Candida spp.
AB - In vitro combination testing with broth microdilution chequerboard (CHEQ) method
is widely used although it is time-consuming, cumbersome and difficult to apply
in routine setting of clinical microbiology laboratory. A new gradient
concentration paper strip method, the Liofilchem((r)) MIC test strips (MTS),
provides an alternative easy and fast method enabling the simultaneous diffusion
of both drugs in combination. We therefore tested a polyene+azole and an
azole+echinocandin combination against 18 Candida isolates with the CHEQ method
based on EUCAST guidelines and the MTS method in research and routine settings.
Fractional inhibitory concentration (FIC) indices were calculated after 24 and 48
h of incubation based on complete and prominent (FIC-2) growth inhibition
endpoints. Reproducibility and agreement within 1 twofold dilution was assessed.
The FICs of the two methods were correlated quantitatively with t-test and
Pearson analysis and qualitatively with Chi-squared test. The reproducibility of
the CHEQ and MTS method was 88-100% and their agreement was 80% with 62-77% of
MTS FICs being higher than the corresponding CHEQ FICs. A statistically
significant Pearson correlation (r = 0.86, P = 0.0003) and association (chi(2) =
17.05, df = 4, P = 0.002) was found between MTS FIC and CHEQ FIC-2 after 24 h.
Categorical agreement was 63% with no very major or major errors. All MTS
synergistic interactions were also synergistic with the CHEQ method.
PMID- 26423199
TI - Redescription and life cycle of the monorchiid Postmonorcheides maclovini Szidat,
1950 (Digenea) from the Southwestern Atlantic Ocean: Morphological and molecular
data.
AB - The adult monorchiid, Postmonorcheides maclovini Szidat, 1950, digenean parasite
of the Patagonian blennie Eleginops maclovinus (Cuvier) (Eleginopidae) from
Puerto Deseado (47 degrees 45' S, 65 degrees 55' W), Argentina, was
characterized and its life cycle elucidated. P. maclovinus is the only species of
the genus Postmonorcheides, proposed by Szidat (1950) from Tierra del Fuego
province (~54 degrees S), Argentina. This digenean uses the Patagonian blennie
as definitive host, and the intertidal bivalve Lasaea adansoni (Gmelin)
(Lasaeidae) as both first and second intermediate hosts (metacercariae encyst
inside sporocysts), being the first record of this clam as intermediate host of
trematode parasites. The cercaria may, in addition to encysting in the sporocyst,
emerge and presumably infect other intermediate hosts. This is the second report
of a monorchiid species with metacercariae encysting inside the sporocyst. Adults
were found parasitizing the fish stomach, pyloric caeca and intestine with a
prevalence of 100%; sporocysts with cercariae and/or metacercariae were found
parasitizing the gonad of the bivalve with a prevalence of 2.78%. The cercariae
possess a well-developed tail and eye-spots are absent. The ITS1 sequence from
the adult digeneans found in the Patagonian blennie, identified as P. maclovini,
was found to be identical to the ITS1 sequences obtained both from sporocysts
containing cercariae and encysted metacercariae found in L. adansoni.
PMID- 26423200
TI - Transition-Metal-Catalyzed Cleavage of C-N Single Bonds.
PMID- 26423201
TI - Persistent Left Ventricular Apical Ballooning Induced by Right Ventricular Apical
Pacing.
PMID- 26423202
TI - A Neutral Silicon/Phosphorus Frustrated Lewis Pair.
AB - Frustrated Lewis pairs (FLPs) have a great potential for activation of small
molecules. Most known FLP systems are based on boron or aluminum atoms as acid
functions, few on zinc, and only two on boron-isoelectronic silicenium cation
systems. The first FLP system based on a neutral silane, (C2F5)3SiCH2P(tBu)2 (1),
was prepared from (C2F5)3SiCl with C2F5 groups of very high electronegativity and
LiCH2P(tBu)2. 1 is capable of cleaving hydrogen, and adds CO2 and SO2. Hydrogen
splitting was confirmed by H/D scrambling reactions. The structures of 1, its CO2
and SO2 adducts, and a decomposition product with CO2 were elucidated by X-ray
diffraction.
PMID- 26423203
TI - A consensus review on the development of palliative care for patients with
chronic and progressive neurological disease.
AB - BACKGROUND AND PURPOSE: The European Association of Palliative Care Taskforce, in
collaboration with the Scientific Panel on Palliative Care in Neurology of the
European Federation of Neurological Societies (now the European Academy of
Neurology), aimed to undertake a review of the literature to establish an
evidence-based consensus for palliative and end of life care for patients with
progressive neurological disease, and their families. METHODS: A search of the
literature yielded 942 articles on this area. These were reviewed by two
investigators to determine the main areas and the subsections. A draft list of
papers supporting the evidence for each area was circulated to the other authors
in an iterative process leading to the agreed recommendations. RESULTS: Overall
there is limited evidence to support the recommendations but there is increasing
evidence that palliative care and a multidisciplinary approach to care do lead to
improved symptoms (Level B) and quality of life of patients and their families
(Level C). The main areas in which consensus was found and recommendations could
be made are in the early integration of palliative care (Level C), involvement of
the wider multidisciplinary team (Level B), communication with patients and
families including advance care planning (Level C), symptom management (Level B),
end of life care (Level C), carer support and training (Level C), and education
for all professionals involved in the care of these patients and families (Good
Practice Point). CONCLUSIONS: The care of patients with progressive neurological
disease and their families continues to improve and develop. There is a pressing
need for increased collaboration between neurology and palliative care.
PMID- 26423204
TI - Prenatal ultrasonographic features of mature cystic teratoma in undescended
testicle.
PMID- 26423205
TI - Improving Procedure Start Times and Decreasing Delays in Interventional
Radiology: A Department's Quality Improvement Initiative.
AB - RATIONALE AND OBJECTIVES: To identify and reduce reasons for delays in procedure
start times, particularly the first cases of the day, within the interventional
radiology (IR) divisions of the Department of Radiology using principles of
continuous quality improvement. MATERIALS AND METHODS: An interdisciplinary team
representative of the IR and preprocedure/postprocedure care area (PPCA) health
care personnel, managers, and data analysts was formed. A standardized form was
used to document both inpatient and outpatient progress through the PPCA and IR
workflow in six rooms and to document reasons for delays. Data generated were
used to identify key problems areas, implement improvement interventions, and
monitor their effects. Project duration was 6 months. RESULTS: The average number
of on-time starts for the first case of the day increased from 23% to 56% (P
value < .01). The average number of on-time, scheduled outpatients increased from
30% to 45% (P value < .01). Patient wait time to arrive at treatment room once
they were ready for their procedure was reduced on average by 10 minutes (P value
< .01). Patient care delay duration per 100 patients was reduced from 30.3 to
21.6 hours (29% reduction). Number of patient care delays per 100 patients was
reduced from 46.6 to 40.1 (17% reduction). Top reasons for delay included waiting
for consent (26% of delays duration) and laboratory tests (12%). CONCLUSIONS:
Many complex factors contribute to procedure start time delays within an IR
practice. A data-driven and patient-centered, interdisciplinary team approach was
effective in reducing delays in IR.
PMID- 26423206
TI - Placental inflammation is not increased in inflammatory bowel disease.
AB - BACKGROUND: Women with inflammatory bowel disease (IBD) are at increased risk for
adverse birth outcomes such as preterm delivery and small for gestational age
(SGA) infants. Most recognized cases of fetal growth restriction in singleton
pregnancies have underlying placental causes. However, studies in IBD examining
poor birth outcomes have focused on maternal factors. We examined whether women
with IBD have a higher rate of placental inflammation than non-IBD controls.
METHODS: Between 2008 and 2011, the placental tissue of 7 ulcerative colitis, 5
Crohn's disease, and 2 IBD-unclassified subjects enrolled in the Pregnancy in
Inflammatory Bowel Disease and Neonatal Outcome (PIANO) registry were evaluated
for villitis, deciduitis, and chorioamnionitis with/without a fetal inflammatory
response. The history and birth outcomes of all IBD subjects were reviewed and
matched to 26 non-IBD controls by gestational age at delivery. RESULTS: Of women
with IBD, 29% delivered preterm infants and 21% delivered SGA infants. Half of
the IBD patients had mild-moderate disease flares during pregnancy. Five (36%)
patients required corticosteroids, 2 (14%) were maintained on an immunomodulator,
and 3 (21%) others received tumor necrosis factor-alpha inhibitors during their
pregnancy. Chorioamnionitis was the only identified placental pathology present
in the placentas reviewed, occurring less frequently in cases compared to
controls (7% vs. 27%, P=0.32). CONCLUSIONS: Placental inflammatory activation
does not appear to be responsible for the increase in adverse birth outcome in
women with IBD. Further studies are necessary to validate these findings in IBD
to explain poor birth outcomes.
PMID- 26423207
TI - Effects of Cyanidin-3-O-glucoside on Synthetic and Metabolic Activity of Ethanol
Stimulated Human Pancreatic Stellate Cells.
AB - Activated pancreatic stellate cells (PSC) play a major role in the development of
chronic pancreatitis. Flavonoids (C-3-O-G) theoretically may have potential to
suppress activated PSC. The aim of our study was to determine the ability of C-3
O-G to invert synthetic and metabolic activity of alcohol stimulated human
pancreatic stellate cells (hPSC). In the present study we demonstrate that
treatment with C-3-O-G decreased proliferation rate of ethanol activated hPSC by
51%. Synthesis of extracellular matrix proteins in activated hPSC was markedly
inhibited, as shown by reduced levels of collagen I and fibronectin expression.
The decrease of secretion of fibronectin by 33% and in collagen I-25% in ethanol
activated and C-3-O-G treated hPSC was observed. Moreover, treatment of ethanol
activated hPSC with C-3-O-G resulted in the decrease of oxygen consumption rate
by 44% and reduced levels of ATP synthesis (i.e. energy production) by 41%.
Hence, the effects of C-3-O-G on ethanol activated hPSC may provide new insights
for the use of anthocyanins as anti-fibrogenic agents in treatment and/or
prevention of pancreatic fibrosis.
PMID- 26423208
TI - Newborn screening for homocystinuria.
AB - BACKGROUND: Homocystinuria is a rare inherited disorder due to a deficiency in
cystathionine beta synthase. Individuals with this condition appear normal at
birth but develop serious complications in childhood. Diagnosis and treatment
started sufficiently early in life can effectively prevent or reduce the severity
of these complications. This is an update of a previously published review.
OBJECTIVES: To determine if newborn population screening for the diagnosis of
homocystinuria due to cystathionine beta synthase deficiency leads to clinical
benefit compared to later clinical diagnosis. SEARCH METHODS: We searched the
Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of
Metabolism Trials Register.Date of the most recent search of the Inborn Errors of
Metabolism Register: 08 June 2015. SELECTION CRITERIA: Randomised controlled
trials and controlled clinical trials assessing the use of any neonatal screening
test to diagnose infants with homocystinuria before the condition becomes
clinically evident. Eligible studies compare a screened population versus a non
screened population. DATA COLLECTION AND ANALYSIS: No studies were identified for
inclusion in the review. MAIN RESULTS: No studies were identified for inclusion
in the review. AUTHORS' CONCLUSIONS: We were unable to identify eligible studies
for inclusion in this review and hence it is not possible to draw any conclusions
based on controlled studies; however, we are aware of uncontrolled case-series
which support the efficacy of newborn screening for homocystinuria and its early
treatment. Any future randomised controlled trial would need to be both
multicentre and long term in order to provide robust evidence for or against
screening and to allow a cost effectiveness analysis to be undertaken.
PMID- 26423210
TI - Adolescent presentations with alcohol intoxication to the emergency department at
Joondalup Health Campus in 2013.
AB - OBJECTIVE: To document the number of adolescents aged 16 years and under
presenting to the ED at Joondalup Health Campus (JHC) with problems related
primarily to alcohol intoxication, and document information about these
presentations. METHOD: Presentations of adolescents were sourced from the
Emergency Department Information System database at JHC. The patient's notes were
interrogated for data on presentation and discharge times, means of arrival to
the ED, age, gender, arrival Glasgow Coma Score (GCS), location from where the
adolescent was brought and blood alcohol levels (BALs), if done. These were
analysed, and descriptive statistics was reported. RESULTS: Fifty-six adolescents
(61% girls) were brought in to JHC ED with alcohol intoxication in 2013. The
majority (76.8%) arrived between 21.00 hours and 05.00 hours, most often by
ambulance or police (58.9%). Most adolescents had BALs performed (80.4%) and of
those, nearly seven in eight (86.7%) had a BAL >0.1 g/L, with a mean of 0.161 g/L
(SD 0.066). Girls had a lower mean BAL, but 26.5% presented with a GCS <14. Most
16 year olds were brought from organised parties, whereas other age groups were
more likely drinking at a friend's house or with friends. Few (12.5%) were
drinking at home. CONCLUSION: Adolescents requiring review in an ED for alcohol
intoxication are most often brought in by ambulance or police in the late evening
or early morning. They are most likely to have high BALs and a significant
proportion will have a GCS <14.
PMID- 26423209
TI - Extending DerSimonian and Laird's methodology to perform network meta-analyses
with random inconsistency effects.
AB - Network meta-analysis is becoming more popular as a way to compare multiple
treatments simultaneously. Here, we develop a new estimation method for fitting
models for network meta-analysis with random inconsistency effects. This method
is an extension of the procedure originally proposed by DerSimonian and Laird.
Our methodology allows for inconsistency within the network. The proposed
procedure is semi-parametric, non-iterative, fast and highly accessible to
applied researchers. The methodology is found to perform satisfactorily in a
simulation study provided that the sample size is large enough and the extent of
the inconsistency is not very severe. We apply our approach to two real examples.
PMID- 26423211
TI - Choosing sides: making decisions in an escape response.
PMID- 26423212
TI - Convenient and Simple Esterification in Continuous-Flow Systems using g-DMAP.
AB - The utility and applicability of polyethylene-g-polyacrylic acid-immobilized
dimethylaminopyridine (g-DMAP) as a catalyst in a continuous-flow system were
investigated for decarboxylative esterification. High catalytic activity toward
acylation was provided by g-DMAP containing a flexible grafted-polymer structure.
During decarboxylation, carboxylic acids and alcohols were converted cleanly
using di-tert-butyl dicarbonate (Boc2O) as a coupling reagent, which reduced by
products. In addition, the use of Boc2O resulted in the formation of tert-butyl
esters. These esterifications dramatically reduced the reaction time under
continuous-flow conditions, with a residence time of approximately 2 min. This
highly efficient esterification procedure will provide more practical industrial
applications.
PMID- 26423214
TI - Synthesis of 2-Nickela(II)oxetanes from Nickel(0) and Epoxides: Structure,
Reactivity, and a New Mechanism of Formation.
AB - 2-Nickelaoxetanes have been frequently invoked as reactive intermediates in
catalytic reactions of epoxides using nickel, but have never been isolated or
experimentally observed in these transformations. Herein, we report the
preparation of a series of well-defined nickelaoxetanes formed via the oxidative
addition of nickel(0) with epoxides featuring ketones. The stereochemistry of the
products is retained, which has not yet been reported for nickelaoxetanes.
Theoretical calculations support a bimetallic ring-opening/closing pathway over a
concerted oxidative addition. Initial reactivity studies of a nickelaoxetane
demonstrated protonolysis, oxidatively induced reductive elimination,
deoxygenation, and elimination reactions when treated with the appropriate
reagents.
PMID- 26423213
TI - Anomalous Evidence, Confidence Change, and Theory Change.
AB - A novel experimental paradigm that measured theory change and confidence in
participants' theories was used in three experiments to test the effects of
anomalous evidence. Experiment 1 varied the amount of anomalous evidence to see
if "dose size" made incremental changes in confidence toward theory change.
Experiment 2 varied whether anomalous evidence was convergent (of multiple types)
or replicating (similar finding repeated). Experiment 3 varied whether
participants were provided with an alternative theory that explained the
anomalous evidence. All experiments showed that participants' confidence changes
were commensurate with the amount of anomalous evidence presented, and that
larger decreases in confidence predicted theory changes. Convergent evidence and
the presentation of an alternative theory led to larger confidence change.
Convergent evidence also caused more theory changes. Even when people do not
change theories, factors pertinent to the evidence and alternative theories
decrease their confidence in their current theory and move them incrementally
closer to theory change.
PMID- 26423215
TI - Recurrent myocardial infarctions and premature coronary atherosclerosis in a 23
year-old man with antiphospholipid syndrome.
PMID- 26423216
TI - Laparoscopic and robotic hepatectomy: experience from a single centre.
AB - BACKGROUND: Both laparoscopic and robotic hepatectomy have been adopted in our
centre for selected patients with benign or malignant liver diseases. This
article reports the perioperative outcomes of these two approaches and tries to
determine any difference between them. METHODS: A retrospective review of
prospectively collected data was performed for all patients who underwent
laparoscopic hepatectomy (LH) and robotic hepatectomy (RH) in our institute. The
perioperative results were reported and compared. In order to standardise the
type of liver resection performed, a subgroup analysis was made for laparoscopic
left lateral sectionectomy (LS) and robotic left lateral sectionectomy (RS).
RESULTS: Sixty-six LH and 70 RH were performed between November 2003 and January
2015. The two groups were comparable in demographic data and disease
characteristics except more patient with recurrent pyogenic cholangitis (RPC)
occurred in RH group. More major hepatectomies were performed in RH (20.0% versus
3.0%, P = 0.002). There was no mortality. No difference was noted in morbidity
(LH 4.5%, RH 11.4%), conversion rate (LH 12.1%, RH 5.7%), median blood loss (both
100 mL) and median length of post-operative hospital stay (both 5 days) but
operative time was longer in RH (251.5 min versus 215 min, P = 0.008). There were
29 LS and 38 RS, no difference was noted in all perioperative outcomes between
the two groups. CONCLUSION: Both laparoscopic and robotic hepatectomy are safe
and their perioperative outcomes are comparable and favourable.
PMID- 26423217
TI - Profiling of EBV-Encoded microRNAs in EBV-Associated Hemophagocytic
Lymphohistiocytosis.
AB - Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a
life-threatening complication of EBV infection. MicroRNAs (miRNAs) were small non
coding RNA, and EBV could encode miRNAs that are involved in the progression of
infection. However, the profiles of EBV-miRNAs in EBV-HLH were unknown. Here, we
aimed to profile the expression of EBV-miRNAs in children with EBV-HLH by
analyzing 44 known EBV-miRNAs, encoded within the BamHI fragment H rightward open
reading frame 1 (BHRF1) and the BamHI-A region rightward transcript (BART), in
plasma and cellular targets by real-time quantitative PCR. The study included 15
children with EBV-HLH, 15 children with infectious mononucleosis (IM), and 15
healthy controls. CD8(+) T cells were found to be the cellular target of EBV
infection in EBV-HLH, while CD19(+) B cells were infected with EBV in IM. We also
found the greater levels of several miRNAs encoded by BART in EBV-HLH, compared
to those in IM and healthy controls, whereas the levels of BHRF1 miRNAs were
lower than those in IM. The profile and pattern of EBV-miRNAs in EBV-HLH
indicated that EBV could display type II latency in EBV-HLH. Importantly, the
level of plasma miR-BART16-1 continued decreasing during the whole chemotherapy,
suggesting that plasma miR-BART16-1 could be a potential biomarker for monitoring
EBV-HLH progression. The pathogenesis of EBV-HLH might be attributed to the
abundance of EBV-miRNAs in EBV-HLH. These findings help elucidate the roles of
EBV miRNAs in EBV-HLH, enabling the understanding of the basis of this disease
and providing clues for its treatment.
PMID- 26423218
TI - Structured Biodegradable Polymeric Microparticles for Drug Delivery Produced
Using Flow Focusing Glass Microfluidic Devices.
AB - Biodegradable poly(DL-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA)
microparticles with tunable size, shape, internal structure and surface
morphology were produced by counter-current flow focusing in axisymmetric (3D)
glass capillary devices. The dispersed phase was composed of 0.5-2 wt % polymer
solution in a volatile organic solvent (ethyl acetate or dichloromethane) and the
continuous phase was 5 wt % aqueous poly(vinyl alcohol) solution. The droplets
with a coefficient of variation in dripping regime below 2.5% were evaporated to
form polymeric particles with uniform sizes ranging between 4 and 30 MUm. The
particle microstructure and surface roughness were modified by adding nanofiller
(montmorillonite nanoclay) or porogen (2-methylpentane) in the dispersed phase to
form less porous polymer matrix or porous particles with golf-ball-like dimpled
surface, respectively. The presence of 2-4 wt % nanoclay in the host polymer
significantly reduced the release rate of paracetamol and prevented the early
burst release, as a result of reduced polymer porosity and tortuous path for the
diffusing drug molecules. Numerical modeling results using the volume of fluid
continuum surface force model agreed well with experimental behavior and revealed
trapping of nanoclay particles in the dispersed phase upstream of the orifice at
low dispersed phase flow rates and for 4 wt % nanoclay content, due to vortex
formation. Janus PLA/PCL (polycaprolactone) particles were produced by solvent
evaporation-induced phase separation within organic phase droplets containing 3%
(v/v) PLA/PCL (30/70 or 70/30) mixture in dichloromethane. A strong preferential
adsorption of Rhodamine 6G dye onto PLA was utilized to identify PLA portions of
the Janus particles by confocal laser scanning microscopy (CLSM). Uniform
hemispherical PCL particles were produced by dissolution of PLA domes with
acetone.
PMID- 26423219
TI - Nonretinotopic visual processing in the brain.
AB - A basic principle in visual neuroscience is the retinotopic organization of
neural receptive fields. Here, we review behavioral, neurophysiological, and
neuroimaging evidence for nonretinotopic processing of visual stimuli. A number
of behavioral studies have shown perception depending on object or external-space
coordinate systems, in addition to retinal coordinates. Both single-cell
neurophysiology and neuroimaging have provided evidence for the modulation of
neural firing by gaze position and processing of visual information based on
craniotopic or spatiotopic coordinates. Transient remapping of the spatial and
temporal properties of neurons contingent on saccadic eye movements has been
demonstrated in visual cortex, as well as frontal and parietal areas involved in
saliency/priority maps, and is a good candidate to mediate some of the spatial
invariance demonstrated by perception. Recent studies suggest that spatiotopic
selectivity depends on a low spatial resolution system of maps that operates over
a longer time frame than retinotopic processing and is strongly modulated by high
level cognitive factors such as attention. The interaction of an initial and
rapid retinotopic processing stage, tied to new fixations, and a longer lasting
but less precise nonretinotopic level of visual representation could underlie the
perception of both a detailed and a stable visual world across saccadic eye
movements.
PMID- 26423220
TI - Systematic psychosocial screening in a paediatric cardiology clinic: clinical
utility of the Pediatric Symptom Checklist 17.
AB - OBJECTIVE: To examine the clinical utility of the Pediatric Symptom Checklist 17
for identifying psychosocial concerns and improving access to psychology services
within a paediatric cardiology clinic. METHOD: Parents of 561 children (aged 4-17
years) presenting for follow-up of CHD, acquired heart disease, or arrhythmia
completed the Pediatric Symptom Checklist 17 as part of routine care; three items
assessing parental (1) concern for learning/development, (2) questions about
adjustment to cardiac diagnosis, and (3) interest in discussing concerns with a
behavioural healthcare specialist were added to the questionnaire. A psychologist
contacted the parents by phone if they indicated interest in speaking with a
behavioural healthcare specialist. RESULTS: Percentages of children scoring above
clinical cut-offs for externalising (10.5%), attention (8.7%), and total (9.3%)
problems were similar to a "normative" primary-care sample, whereas fewer
children in this study scored above the cut-off for internalising problems (7.8%;
p<0.01). Sociodemographic, but not clinical, characteristics were associated with
Pediatric Symptom Checklist 17 scores. 17% of the parents endorsed concerns about
learning/development, and 20% endorsed questions about adjustment to diagnosis.
History of cardiac surgery was associated with increased concern about
learning/development (p<0.01). Only 37% of the parents expressing psychosocial
concerns reported interest in speaking with a psychologist. CONCLUSIONS: The
Pediatric Symptom Checklist 17 may not be sensitive to specific difficulties
experienced by this patient population. A questionnaire with greater focus on
learning/development and adjustment to diagnosis may yield improved utility.
Psychology integration in clinics serving high-risk cardiac patients may decrease
barriers to behavioural healthcare services.
PMID- 26423221
TI - Computational identification of genetic subnetwork modules associated with maize
defense response to Fusarium verticillioides.
AB - BACKGROUND: Maize, a crop of global significance, is vulnerable to a variety of
biotic stresses resulting in economic losses. Fusarium verticillioides
(teleomorph Gibberella moniliformis) is one of the key fungal pathogens of maize,
causing ear rots and stalk rots. To better understand the genetic mechanisms
involved in maize defense as well as F. verticillioides virulence, a systematic
investigation of the host-pathogen interaction is needed. The aim of this study
was to computationally identify potential maize subnetwork modules associated
with its defense response against F. verticillioides. RESULTS: We obtained time
course RNA-seq data from B73 maize inoculated with wild type F. verticillioides
and a loss-of-virulence mutant, and subsequently established a computational
pipeline for network-based comparative analysis. Specifically, we first analyzed
the RNA-seq data by a cointegration-correlation-expression approach, where maize
genes were jointly analyzed with known F. verticillioides virulence genes to find
candidate maize genes likely associated with the defense mechanism. We predicted
maize co-expression networks around the selected maize candidate genes based on
partial correlation, and subsequently searched for subnetwork modules that were
differentially activated when inoculated with two different fungal strains. Based
on our analysis pipeline, we identified four potential maize defense subnetwork
modules. Two were directly associated with maize defense response and were
associated with significant GO terms such as GO:0009817 (defense response to
fungus) and GO:0009620 (response to fungus). The other two predicted modules were
indirectly involved in the defense response, where the most significant GO terms
associated with these modules were GO:0046914 (transition metal ion binding) and
GO:0046686 (response to cadmium ion). CONCLUSION: Through our RNA-seq data
analysis, we have shown that a network-based approach can enhance our
understanding of the complicated host-pathogen interactions between maize and F.
verticillioides by interpreting the transcriptome data in a system-oriented
manner. We expect that the proposed analytic pipeline can also be adapted for
investigating potential functional modules associated with host defense response
in diverse plant-pathogen interactions.
PMID- 26423222
TI - Controllability of structural brain networks.
AB - Cognitive function is driven by dynamic interactions between large-scale neural
circuits or networks, enabling behaviour. However, fundamental principles
constraining these dynamic network processes have remained elusive. Here we use
tools from control and network theories to offer a mechanistic explanation for
how the brain moves between cognitive states drawn from the network organization
of white matter microstructure. Our results suggest that densely connected areas,
particularly in the default mode system, facilitate the movement of the brain to
many easily reachable states. Weakly connected areas, particularly in cognitive
control systems, facilitate the movement of the brain to difficult-to-reach
states. Areas located on the boundary between network communities, particularly
in attentional control systems, facilitate the integration or segregation of
diverse cognitive systems. Our results suggest that structural network
differences between cognitive circuits dictate their distinct roles in
controlling trajectories of brain network function.
PMID- 26423223
TI - Seroepidemiology of mumps in the general population of Jiangsu province, China
after introduction of a one-dose measles-mumps-rubella vaccine.
AB - The mumps surveillance data from 2004 to 2011 showed that the incidence of mumps
remained high after the one-dose measles-mumps-rubella (MMR) vaccine was
introduced in China in 2008. A cross-sectional survey of mumps IgG in the general
population of Jiangsu province was conducted in 2012 to gain comprehensive
information on the immunity profile of the general population. The mean incidence
was 15.2 per 100 000 individuals in Jiangsu province from 2004-2013. Two mumps
incidence peaks were observed each year after introduction of the one-dose MMR
vaccine. The seroprevalence did not significantly differ by region or sex, while
the GMC significantly differed by region and sex. The overall GMC in Jiangsu
province was 99.1 IU/ml (95% CI: 90.1-108.2), while the seroprevalence was only
59.1% (95% CI: 56.5-61.6). The seroprevalences for the 2 age groups that received
the one-dose MMR vaccine, with reported coverage exceeding 95%, were 42.6% and
70.0%, respectively. The data on the incidence, MMR coverage, and seroprevalence
in children younger than 6 years of age indicate that a two-dose MMR strategy
should be considered. Mumps surveillance should be strengthened in children aged
6-11 and in those aged 12-17 because of their high contact rates and relatively
low seroprevalences.
PMID- 26423224
TI - Volatile fragrances associated with flowers mediate host plant alternation of a
polyphagous mirid bug.
AB - Apolygus lucorum (Hemiptera: Miridae) is an important insect pest of cotton and
fruit trees in China. The adults prefer host plants at the flowering stage, and
their populations track flowering plants both spatially and temporally. In this
study, we examine whether flower preference of its adults is mediated by plant
volatiles, and which volatile compositions play an important role in attracting
them. In olfactometer tests with 18 key host species, the adults preferred
flowering plants over non-flowering plants of each species. Coupled gas
chromatography-electroantennography revealed the presence of seven
electrophysiologically active compounds from flowering plants. Although the
adults responded to all seven synthetic plant volatiles in electroantennography
tests, only four (m-xylene, butyl acrylate, butyl propionate and butyl butyrate)
elicited positive behavioral responses in Y-tube olfactometer bioassays. The
adults were strongly attracted to these four active volatiles in multi-year
laboratory and field trials. Our results suggest that these four fragrant
volatiles, which are emitted in greater amounts once plants begin to flower,
mediate A. lucorum's preference to flowering host plants. We proved that the use
of commonly occurring plant volatiles to recognize a large range of plant species
can facilitate host selection and preference of polyphagous insect herbivore.
PMID- 26423225
TI - Antiviral therapy leads to histological improvement in HBeAg-negative chronic
hepatitis B patients.
PMID- 26423226
TI - Navigating through digital folders uses the same brain structures as real world
navigation.
AB - Efficient storage and retrieval of digital data is the focus of much commercial
and academic attention. With personal computers, there are two main ways to
retrieve files: hierarchical navigation and query-based search. In navigation,
users move down their virtual folder hierarchy until they reach the folder in
which the target item is stored. When searching, users first generate a query
specifying some property of the target file (e.g., a word it contains), and then
select the relevant file when the search engine returns a set of results. Despite
advances in search technology, users prefer retrieving files using virtual folder
navigation, rather than the more flexible query-based search. Using fMRI we
provide an explanation for this phenomenon by demonstrating that folder
navigation results in activation of the posterior limbic (including the
retrosplenial cortex) and parahippocampal regions similar to that previously
observed during real-world navigation in both animals and humans. In contrast,
search activates the left inferior frontal gyrus, commonly observed in linguistic
processing. We suggest that the preference for navigation may be due to the
triggering of automatic object finding routines and lower dependence on
linguistic processing. We conclude with suggestions for future computer systems
design.
PMID- 26423227
TI - Three-dimensional matrix fiber alignment modulates cell migration and MT1-MMP
utility by spatially and temporally directing protrusions.
AB - Multiple attributes of the three-dimensional (3D) extracellular matrix (ECM) have
been independently implicated as regulators of cell motility, including pore
size, crosslink density, structural organization, and stiffness. However, these
parameters cannot be independently varied within a complex 3D ECM protein
network. We present an integrated, quantitative study of these parameters across
a broad range of complex matrix configurations using self-assembling 3D collagen
and show how each parameter relates to the others and to cell motility.
Increasing collagen density resulted in a decrease and then an increase in both
pore size and fiber alignment, which both correlated significantly with cell
motility but not bulk matrix stiffness within the range tested. However, using
the crosslinking enzyme Transglutaminase II to alter microstructure independently
of density revealed that motility is most significantly predicted by fiber
alignment. Cellular protrusion rate, protrusion orientation, speed of migration,
and invasion distance showed coupled biphasic responses to increasing collagen
density not predicted by 2D models or by stiffness, but instead by fiber
alignment. The requirement of matrix metalloproteinase (MMP) activity was also
observed to depend on microstructure, and a threshold of MMP utility was
identified. Our results suggest that fiber topography guides protrusions and
thereby MMP activity and motility.
PMID- 26423230
TI - INEBRIA 12th Congress.
PMID- 26423228
TI - Anti-interleukin-6 therapy through application of a monogenic protein inhibitor
via gene delivery.
AB - Anti-cytokine therapies have substantially improved the treatment of inflammatory
and autoimmune diseases. Cytokine-targeting drugs are usually biologics such as
antibodies or other engineered proteins. Production of biologics, however, is
complex and intricate and therefore expensive which might limit therapeutic
application. To overcome this limitation we developed a strategy that involves
the design of an optimized, monogenic cytokine inhibitor and the protein
producing capacity of the host. Here, we engineered and characterized a receptor
fusion protein, mIL-6-RFP-Fc, for the inhibition of interleukin-6 (IL-6), a well
established target in anti-cytokine therapy. Upon application in mice mIL-6-RFP
Fc inhibited IL-6-induced activation of the transcription factor STAT3 and ERK1/2
kinases in liver and kidney. mIL-6-RFP-Fc is encoded by a single gene and
therefore most relevant for gene transfer approaches. Gene transfer through
hydrodynamic plasmid delivery in mice resulted in hepatic production and
secretion of mIL-6-RFP-Fc into the blood in considerable amounts, blocked hepatic
acute phase protein synthesis and improved kidney function in an ischemia and
reperfusion injury model. Our study establishes receptor fusion proteins as
promising agents in anti-cytokine therapies through gene therapeutic approaches
for future targeted and cost-effective treatments. The strategy described here is
applicable for many cytokines involved in inflammatory and other diseases.
PMID- 26423229
TI - Eastern equine encephalitis virus in mice II: pathogenesis is dependent on route
of exposure.
AB - BACKGROUND: Eastern equine encephalitis virus (EEEV) is an alphavirus with a case
fatality rate estimated to be as high as 75 % in humans and 90 % in horses.
Surviving patients often have long-lasting and severe neurological sequelae. At
present, there is no licensed vaccine or therapeutic for EEEV infection. This
study completes the clinical and pathological analysis of mice infected with a
North American strain of EEEV by three different routes: aerosol, intranasal, and
subcutaneous. Such an understanding is imperative for use of the mouse model in
vaccine and antiviral drug development. METHODS: Twelve-week-old female BALB/c
mice were infected with EEEV strain FL93-939 by the intranasal, aerosol, or
subcutaneous route. Mice were euthanized 6 hpi through 8 dpi and tissues were
harvested for histopathological and immunohistochemical analysis. RESULTS: Viral
antigen was detected in the olfactory bulb as early as 1-2 dpi in aerosol and
intranasal infected mice. However, histologic lesions in the brain were evident
about 24 hours earlier (3 dpi vs 4 dpi), and were more pronounced following
aerosol infection relative to intranasal infection. Following subcutaneous
infection, viral antigen was also detected in the olfactory bulb, though not as
routinely or as early. Significant histologic lesions were not observed until 6
dpi. CONCLUSION: These pathologic studies suggest EEEV enters the brain through
the olfactory system when mice are exposed via the intranasal and aerosol routes.
In contrast, the histopathologic lesions were delayed in the subcutaneous group
and it appears the virus may utilize both the vascular and olfactory routes to
enter the brain when mice are exposed to EEEV subcutaneously.
PMID- 26423231
TI - Can dietary selenium intake increase the risk of toxicity in healthy children?
PMID- 26423233
TI - Omics Approaches Deciphering Molecular Function in Large Biological Systems.
PMID- 26423232
TI - Herbal supplement Kamishimotsuto augments resistance exercise-induced mTORC1
signaling in rat skeletal muscle.
AB - OBJECTIVES: Kamishimotsuto (KST) is a supplement containing 13 different herbs
including Phellodendron bark, Anemarrhena rhizome and ginseng that have been
shown to activate mammalian target of rapamycin complex 1 (mTORC1) and thereby
increase muscle protein synthesis in vitro. However, the combined effect of KST
and resistance exercise on muscle protein anabolism has not been investigated in
vivo. Therefore, the purpose of this study was to investigate the effect of KST
supplementation, resistance exercise on (mTORC1) signaling and subsequent muscle
protein synthesis. METHODS: Male Sprague-Dawley rats were divided into two
groups: one group received KST (500 mg/kg/d in water) and the other group
received placebo (PLA) for 7 d. After 12 h of fasting, the right gastrocnemius
muscle was isometrically exercised via percutaneous electrical stimulation.
Muscle samples were analyzed for muscle protein synthesis (MPS) and by western
blotting analysis to assess the phosphorylation of p70S6K (Thr389), rpS6
(Ser240/244), and Akt (Ser473 and Thr308). RESULTS: KST supplementation for 7 d
significantly increased basal p-Akt (Ser473) levels compared with PLA,
phosphorylation of the signaling proteins and MPS at baseline were otherwise
unaffected. p-p70S6K and p-rpS6 levels significantly increased 1 h and 3 h after
exercise in the PLA group, and these elevations were augmented in the KST group
(P < 0.05). Furthermore, MPS at 6 h after resistance exercise was greater in the
KST group than in the PLA group (P < 0.05). CONCLUSIONS: While resistance
exercise alone was able to increase p70S6K and rpS6 phosphorylation,
Kamishimotsuto supplementation further augmented resistance exercise-induced
muscle protein synthesis through mTORC1 signaling.
PMID- 26423234
TI - Nuclear Reformation at the End of Mitosis.
AB - Cells have developed highly sophisticated ways to accurately pass on their
genetic information to the daughter cells. In animal cells, which undergo open
mitosis, the nuclear envelope breaks down at the beginning of mitosis and the
chromatin massively condenses to be captured and segregated by the mitotic
spindle. These events have to be reverted in order to allow the reformation of a
nucleus competent for DNA transcription and replication, as well as all other
nuclear processes occurring in interphase. Here, we summarize our current
knowledge of how, in animal cells, the highly compacted mitotic chromosomes are
decondensed at the end of mitosis and how a nuclear envelope, including
functional nuclear pore complexes, reassembles around these decondensing
chromosomes.
PMID- 26423235
TI - A new classification of interphase nuclei based on spatial organizations of
chromosome 8 and 21 for t(8;21) (q22;q22) acute myeloid leukemia by three
dimensional fluorescence in situ hybridization.
AB - Interphase heterogenous chromosomes spatially close to each other are
predominantly located near the center of nuclei and are prone to incur
translocations. We screened a t(8;21) (q22;q22) acute myeloid leukemia-M2 patient
during three phases (post-chemotherapy, remittent stage, and relapse) and a donor
of normal karyotype as control by two-(2D) and three-dimensional (3D)
fluorescence in situ hybridization (FISH). Our classification of nuclei (normal,
transitional, and malignant nuclei) by 3D-FISH analyses may provide a more
precise prognosis than 2D-FISH results, especially for remittent stage sample in
our study, in which 2D-FISH findings showed normal results, whereas 3D-FISH
results showed extreme abnormalities (normal nuclei 27%, transitional nuclei 36%,
malignant nuclei 37%). The relative radial positions (d/R) of chromosomes 8 were
similar to d/R of chromosomes 21 for the relapse sample. We classified
heterogenous chromosome pairs into close pairs and normal pairs based on their
relative distances (d'/(2R)). The centers of close pairs were more internal than
normal pairs in nuclei in all samples, and the d/R values of a given-type
pairwise heterogenous chromosomes were similar among four samples. Our data
demonstrate that the classification of nuclei based on spatial organization of
chromosomes by 3D-FISH is reasonable and essential for evaluating acute myeloid
leukemia prognosis.
PMID- 26423236
TI - In vitro-in vivo correlation of parenteral risperidone polymeric microspheres.
AB - The objective of the present study was to determine whether an in vitro-in vivo
correlation (IVIVC) can be established for polymeric microspheres that are
equivalent in formulation composition but prepared with different manufacturing
processes. Risperidone was chosen as a model therapeutic and poly(lactic-co
glycolic acid) (PLGA) with similar molecular weight as that used in the
commercial product Risperdal(r) Consta(r) was used to prepare risperidone
microspheres. Various manufacturing processes were investigated to produce the
risperidone microspheres with similar drug loading (approx. 37%) but distinctly
different physicochemical properties (e.g. porosity, particle size and particle
size distribution). In vitro release of the risperidone microspheres was
investigated using different release testing methods (such as sample-and-separate
and USP apparatus 4). In vivo pharmacokinetic profiles of the risperidone
microsphere formulations following intramuscular administration were determined
using a rabbit model. Furthermore, the obtained pharmacokinetic profiles were
deconvoluted using the Loo-Riegelman method and the calculated in vivo release
was compared with the in vitro release of these microspheres. Level A IVIVCs were
established and validated for the compositionally equivalent risperidone
microspheres based on the in vitro release data obtained using USP apparatus 4.
The developed IVIVCs demonstrated good predictability and were robust. These
results showed that the developed USP apparatus 4 method was capable of
discriminating PLGA microspheres that are equivalent in formulation composition
but with manufacturing differences and predicting their in vivo performance in
the investigated animal model.
PMID- 26423237
TI - One-component nanomedicine.
AB - One-component nanomedicine (OCN) represents an emerging class of therapeutic
nanostructures that contain only one type of chemical substance. This one
component feature allows for fine-tuning and optimization of the drug loading and
physicochemical properties of nanomedicine in a precise manner through molecular
engineering of the underlying building blocks. Using a precipitation procedure or
effective molecular assembly strategies, molecularly crafted therapeutic agents
(e.g. polymer-drug conjugates, small molecule prodrugs, or drug amphiphiles)
could involuntarily aggregate, or self-assemble into nanoscale objects of well
defined sizes and shapes. Unlike traditional carrier-based nanomedicines that are
inherently multicomponent systems, an OCN does not require the use of additional
carriers and could itself possess desired physicochemical features for
preferential accumulation at target sites. We review here recent progress in the
molecular design, conjugation methods, and fabrication strategies of OCN, and
analyze the opportunities that this emerging platform could open for the new and
improved treatment of devastating diseases such as cancer.
PMID- 26423238
TI - Improving cell-based therapies by nanomodification.
AB - Cell-based therapies are emerging as a promising approach for various diseases.
Their therapeutic efficacy depends on rational control and regulation of the
functions and behaviors of cells during their treatments. Different from
conventional regulatory strategy by chemical adjuvants or genetic engineering,
which is restricted by limited synergistic regulatory efficiency or uncertain
safety problems, a novel approach based on nanoscale artificial materials can be
applied to modify living cells to endow them with novel functions and unique
properties. Inspired by natural "nano shell" and "nano compass" structures, cell
nanomodification can be developed through both external and internal pathways. In
this review, some novel cell surface engineering and intracellular
nanoconjugation strategies are summarized. Their potential applications are also
discussed, including cell protection, cell labeling, targeted delivery and in
situ regulation. It is believed that these novel cell-material complexes can have
great potentials for biomedical applications.
PMID- 26423241
TI - Low-Density Lipoprotein Uptake Demonstrates a Hepatocyte Phenotype in the Dog,
but Is Nonspecific.
AB - Low-density lipoprotein (LDL) uptake is one of a number of tests used to
demonstrate hepatocyte-like function after stem cell differentiation. Use of two
compounds, LDL and acetylated LDL (AcLDL), has been described despite each having
different mechanisms of uptake. Three primary hepatocyte cultures and three sets
of mesenchymal stromal cell (MSC) cultures, derived from both adipose tissue and
bone marrow, were harvested from dogs. Those cells were compared to commercially
available human and mouse bone marrow-derived MSCs. LDL receptor expression was
demonstrated by gene expression and immunofluorescence in all primary hepatocyte
cultures, undifferentiated canine bone marrow MSCs and canine adipose MSCs.
Undifferentiated human and mouse bone marrow MSCs also expressed the LDL
receptor. In vitro, canine hepatocytes took up labeled LDL, but not AcLDL. All
undifferentiated MSCs took up LDL, but not AcLDL. In conclusion, LDL and not
AcLDL is a test of canine hepatocyte-like phenotype, but this is not tissue or
species specific and, therefore, is not informative assay when testing proof of
MSC to hepatocyte differentiation.
PMID- 26423239
TI - Designing polymers with sugar-based advantages for bioactive delivery
applications.
AB - Sugar-based polymers have been extensively explored as a means to increase drug
delivery systems' biocompatibility and biodegradation. Here,we review he use of
sugar-based polymers for drug delivery applications, with a particular focus on
the utility of the sugar component(s) to provide benefits for drug targeting and
stimuli responsive systems. Specifically, numerous synthetic methods have been
developed to reliably modify naturally-occurring polysaccharides, conjugate sugar
moieties to synthetic polymer scaffolds to generate glycopolymers, and utilize
sugars as a multifunctional building block to develop sugar-linked polymers. The
design of sugar-based polymer systems has tremendous implications on both the
physiological and biological properties imparted by the saccharide units and are
unique from synthetic polymers. These features include the ability of
glycopolymers to preferentially target various cell types and tissues through
receptor interactions, exhibit bioadhesion for prolonged residence time, and be
rapidly recognized and internalized by cancer cells. Also discussed are the
distinct stimuli-sensitive properties of saccharide-modified polymers to mediate
drug release under desired conditions. Saccharide-based systems with inherent pH-
and temperature-sensitive properties, as well as enzyme-cleavable polysaccharides
for targeted bioactive delivery, are covered. Overall, this work emphasizes
inherent benefits of sugar-containing polymer systems for bioactive delivery.
PMID- 26423240
TI - Do telomeres have a higher plasticity than thought? Results from the German
Chronic Kidney Disease (GCKD) study as a high-risk population.
AB - Telomere length is considered as a biological marker for aging. It is expected
that telomeres shorten with age and with conditions associated with oxidative
stress and inflammation. Both are present in patients with chronic kidney disease
(CKD) who have a very high cardiovascular risk. We investigated whether CKD
duration is associated with relative telomere length (RTL) in 4802 patients from
the German Chronic Kidney Disease (GCKD) study. We measured RTL in each sample in
quadruplicates using a quantitative polymerase chain reaction (qPCR). We observed
a U-shaped association of RTL with CKD duration: the longest RTL was found in
those 339 patients who reported the shortest disease duration (<6 months) and
shorter RTL in 2108 patients with duration between 6 months and less than 5
years. Most importantly, those 2331 patients who reported a CKD duration of 5
years and more had significantly longer RTL compared to those with intermediate
CKD duration (6 months to less than 5 years): mean 0.954, 95%CI 0.946-0.961
versus 0.937, 95%CI 0.929-0.944, p=0.002). Due to the cross-sectional nature of
the study these surprising results have to be considered with caution and as
hypothesis-generating. Whether the longer RTL in patients with long-lasting
disease is caused by an activation of telomerase to counteract the shortening of
RTL due to oxidative stress and inflammation or whether they are caused by a
survival bias needs to be investigated in longitudinal studies. Our data are in
support of a higher plasticity of shortening and elongations of RTL as until
recently anticipated.
PMID- 26423242
TI - Elevated resting heart rate predisposes metabolic syndrome in women rather than
in men: a 15-year prospective study.
AB - BACKGROUND: Increasing evidences have indicated that there are gender differences
in the prevalence of metabolic syndrome(MS), but the mechanism is uncertain.
METHODS: A total of 711 subjects aged 35-65 years accepted health examinations
both in 1992 and 2007. Since 114 subjects had MS and 7 had heart disease at
baseline, they were excluded from the analysis. Therefore, 590 subjects with
complete data (male: 61.5 %) were available and analysed. After the relationship
between gender and incident MS at follow-up was tested, these subjects were
categorized into four groups according to the baseline resting heart rate(RHR)
classified by genders. Trend tests of MS incidences across the four groups of
resting heart rate were conducted by Cochran-Armitage tend tests in both men and
women. Additionally, three logistic regression models were used to estimate the
effects of RHR on the new onset of MS by taking RHR as a continuous variable(per
4 beats/min elevation). RESULTS: Gender(women) itself was an independent risk
factor for incident MS at follow-up(OR = 2.64, 1.33-5.23, P = 0.005). The
incidences of MS according to the RHR categories showed a statistical linear
trend in women(P for trend = 0.018) rather than in men(P for trend = 0.194). The
ORs[95 % confidence intervals(CIs)] of MS for each 4 bpm elevation in RHR was
1.18(1.03-1.36)(P = 0.020) in a univariate model, 1.20 (1.04-1.38) (P = 0.011)
adjusted for age and health related behaviors only and 1.23(1.06-1.43)(P = 0.007)
adjusted for age, health related behaviors and pre-existing components of MS in
the baseline in women. Otherwise, RHR did not have any significant associations
with incident MS in men neither in a univariate model nor in multivariate models.
CONCLUSIONS: In this study, elevated RHR is correlated with the development of MS
in women rather than in men.
PMID- 26423243
TI - No effect of unemployment on intimate partner-related femicide during the
financial crisis: a longitudinal ecological study in Spain.
AB - BACKGROUND: Spain's financial crisis has been characterized by an increase in
unemployment. This increase could have produced an increase in deaths of women
due to intimate partner-related femicides (IPF). This study aims to determine
whether the increase in unemployment among both sexes in different regions in
Spain is related to an increase in the rates of IPF during the current financial
crisis period. METHODS: An ecological longitudinal study was carried out in
Spain's 17 regions. Two study periods were defined: pre-crisis period (2005-2007)
and crisis period (2008-2013). IPF rates adjusted by age and unemployment rates
for men and women were calculated. We fitted multilevel linear regression models
in which observations at level 1 were nested within regions according to a
repeated measurements design. RESULTS: Rates of unemployment have progressively
increased in Spain, rising above 20 % from 2008 to 2013 in some regions. IPF
rates decreased in some regions during crisis period with respect to pre-crisis
period. The multilevel analysis does not support the existence of a significant
relationship between the increase in unemployment in men and women and the
decrease in IPF since 2008. DISCUSSION: The increase in unemployment in men and
women in Spain does not appear to have an effect on IPF. The results of the
multilevel analysis discard the hypothesis that the increase in the rates of
unemployment in women and men are related to an increase in IPF rates.
CONCLUSIONS: The decline in IPF since 2008 might be interpreted as the result of
exposure to other factors such as the lower frequency of divorces in recent years
or the medium term effects of the integral protection measures of the law on
gender violence that began in 2005.
PMID- 26423244
TI - Fluoroquinolone therapy for bloodstream infections caused by extended-spectrum
beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae.
AB - BACKGROUND/PURPOSE: For extended-spectrum beta-lactamase (ESBL)-producing
Enterobacteriaceae infections, carbapenems are recommended as first line therapy,
and clinical data on the therapeutic efficacy of fluoroquinolones (FQs) is
limited. This study compares the efficacy of FQs and carbapenems for bloodstream
infections caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae.
METHODS: Between 2008 and 2010, adults with ESBL-producing E. coli or K.
pneumoniae bacteremia at two medical centers were reviewed. Adults receiving
definitive FQ or carbapenem therapy were compared in a propensity score-matched
analysis, and 30-day mortality was the primary endpoint. RESULTS: A total of 299
patients were eligible. Patients receiving a FQ (n = 24), either ciprofloxacin or
levofloxacin, had a lower 30-day mortality rate than those with carbapenem
therapy (8.3%, 2/24 vs. 23.3%, 64/275; p = 0.12). Multivariate regression
analysis revealed that a critical illness [Pitt bacteremia score >= 4 points;
odds ratio (OR), 7.09; p < 0.001], rapidly fatal underlying disease (OR, 5.73; p
< 0.001), and hospital-associated infection (OR, 2.57; p = 0.01) were
independently associated with 30-day mortality. By contrast, FQ definitive
therapy was a protective factor compared with carbapenems (OR, 0.18; p = 0.04).
There were 72 matched cases with carbapenem therapy in a propensity score-matched
analysis, and a difference in the 30-day mortality rate of two groups was noted
(8.3% vs. 29.2%; p = 0.05). CONSLUSION: For ESBL-producing E. coli or K.
pneumoniae bacteremia, ciprofloxacin or levofloxacin, if active in vitro, can be
considered as a carbapenem-sparing alternative.
PMID- 26423246
TI - New paediatric formulation is a milestone in treatment.
PMID- 26423245
TI - Histone deacetylase inhibitors and epigenetic regulation in lymphoid
malignancies.
AB - A vast majority of lymphomas and leukaemias are results of translocations. These
translocations produce various genetic and epigenetic changes that lead to
oncogenesis. This opens an opportunity to use a relatively new class of anti
cancer agents, inhibitors of histone deacetylases (HDACi) to target lymphoid
malignancies. Surprisingly, the rational basis for treatment of lymphomas with
HDACi is far from clear, although some positive results have been obtained. Here
we analyze the effect of histone deacetylase (HDAC) inhibitors on lymphoid
malignancies.
PMID- 26423247
TI - ART in sub-Saharan Africa: the value of viral load monitoring.
PMID- 26423248
TI - DMPA use and HIV acquisition: time to switch to NET-EN?
PMID- 26423249
TI - HIV-infection and comorbidities: a complex mix.
PMID- 26423250
TI - Nigeria, MSM, and the law: from evidence to strategy.
PMID- 26423251
TI - Overlap of HIV and low health literacy in the southern USA.
PMID- 26423253
TI - Time trends for risk of severe age-related diseases in individuals with and
without HIV infection in Denmark: a nationwide population-based cohort study.
AB - BACKGROUND: Whether the reported high risk of age-related diseases in HIV
infected people is caused by biological ageing or HIV-associated risk factors
such as chronic immune activation and low-grade inflammation is unknown. We
assessed time trends in age-standardised and relative risks of nine serious age
related diseases in a nationwide cohort study of HIV-infected individuals and
population controls. METHODS: We identified all HIV-infected individuals in the
Danish HIV Cohort Study who had received HIV care in Denmark between Jan 1, 1995,
and June 1, 2014. Population controls were identified from the Danish Civil
Registration System and individually matched in a ratio of nine to one to the HIV
infected individuals for year of birth, sex, and date of study inclusion.
Individuals were included in the study if they had a Danish personal
identification number, were aged 16 years or older, and were living in Denmark at
the time of study inclusion. Data for study outcomes were obtained from the
Danish National Hospital Registry and the Danish National Registry of Causes of
Death and were cardiovascular diseases (myocardial infarction and stroke),
cancers (virus associated, smoking related, and other), severe neurocognitive
disease, chronic kidney disease, chronic liver disease, and osteoporotic
fractures. We calculated excess and age-standardised incidence rates and adjusted
incidence rate ratios of outcomes for time after HIV diagnosis, highly active
antiretroviral therapy (ART) initiation, and calendar time. The regression
analyses were adjusted for age, sex, calendar time, and origin. FINDINGS: We
identified 5897 HIV-infected individuals and 53,073 population controls; median
age was 36.8 years (IQR 30.6-44.4), and 76% were men in both cohorts. Dependent
on disease, the HIV cohort had 55,050-57,631 person-years of follow-up and the
population controls had 638,204-659,237 person-years of follow-up. Compared with
the population controls, people with HIV had high excess and relative risk of all
age-related diseases except other cancers. Overall, the age-standardised and
relative risks of cardiovascular diseases, cancers, and severe neurocognitive
disease did not increase substantially with time after HIV diagnosis or ART
initiation. Except for chronic kidney diseases, the age-standardised and relative
risks of age-related diseases did not increase with calendar time.
INTERPRETATIONS: Severe age-related diseases are highly prevalent in people with
HIV, and continued attention and strategies for risk reduction are needed. The
findings from our study do not suggest that accelerated ageing is a major problem
in the HIV-infected population. FUNDING: Preben og Anna Simonsens Fond, Novo
Nordisk Foundation, Danish AIDS Foundation, Augustinus Foundation, and Odense
University Hospitals Frie Fonds Midler.
PMID- 26423255
TI - The journey of nisin development in China, a natural-green food preservative.
PMID- 26423252
TI - Monitoring and switching of first-line antiretroviral therapy in adult treatment
cohorts in sub-Saharan Africa: collaborative analysis.
AB - BACKGROUND: HIV-1 viral load testing is recommended to monitor antiretroviral
therapy (ART) but is not universally available. The aim of our study was to
assess monitoring of first-line ART and switching to second-line ART in sub
Saharan Africa. METHODS: We did a collaborative analysis of cohort studies from
16 countries in east Africa, southern Africa, and west Africa that participate in
the international epidemiological database to evaluate AIDS (IeDEA). We included
adults infected with HIV-1 who started combination ART between January, 2004, and
January, 2013. We defined switching of ART as a change from a non-nucleoside
reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease
inhibitor, with adjustment of one or more nucleoside reverse-transcriptase
inhibitors (NRTIs). Virological and immunological failures were defined according
to WHO criteria. We calculated cumulative probabilities of switching and hazard
ratios with 95% CIs comparing routine viral load monitoring, targeted viral load
monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and
individual characteristics. FINDINGS: Of 297,825 eligible patients, 10,352 (3%)
switched to second-line ART during 782 ,412 person-years of follow-up. Compared
with CD4 monitoring, hazard ratios for switching were 3.15 (95% CI 2.92-3.40) for
routine viral load monitoring, 1.21 (1.13-1.30) for targeted viral load
monitoring, and 0.49 (0.43-0.56) for clinical monitoring. Of 6450 patients with
confirmed virological failure, 58.0% (95% CI 56.5-59.6) switched by 2 years, and
of 15,892 patients with confirmed immunological failure, 19.3% (18.5-20.0)
switched by 2 years. Of 10,352 patients who switched, evidence of treatment
failure based on one CD4 count or viral load measurement ranged from 86 (32%) of
268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral
load monitoring. Median CD4 counts at switching were 215 cells per MUL (IQR 117
335) with routine viral load monitoring, but were lower with other types of
monitoring (range 114-133 cells per MUL). INTERPRETATION: Overall, few patients
switched to second-line ART and switching happened late in the absence of routine
viral load monitoring. Switching was more common and happened earlier after
initiation of ART with targeted or routine viral load testing. FUNDING: National
Institute of Allergy and Infectious Diseases, Swiss National Science Foundation.
PMID- 26423257
TI - [Not Available].
PMID- 26423256
TI - Macroscopic and microscopic assessments of the glenohumeral and subacromial
synovitis in rotator cuff disease.
AB - BACKGROUND: Whereas synovitis is one of most common findings during arthroscopic
surgery in patients with rotator cuff diseases, no study has investigated its
characteristics. We propose a macroscopic assessment system for investigating the
characteristics of synovitis. METHODS: Fifty-four patients with a full-thickness
rotator cuff tear undergoing arthroscopic rotator cuff repair with an average age
of 62.5 +/- 7.0 years were included. For the macroscopic assessment, 3
parameters, villous hypertrophy, hyperemia, and density, were measured and
translated into grades in 3 regions-of-interest (ROI) in the glenohumeral joint
and 4 ROIs in the subacromial space. For the microscopic assessments, 4 commonly
used microscopic assessment systems were used. The reliability and association
between the macroscopic and microscopic assessments were investigated. RESULTS:
The inter- and intra-observer reliability of all of the macroscopic and
microscopic assessments were excellent. The severity of synovitis was
significantly greater in the glenohumeral joint than that in the subacromial
space, 1.54 +/- 0.61 versus 0.94 +/- 0.56 (p < 0.001). Synovitis varied with
respect to location, and was generally more severe near the tear with the
macroscopic assessment system. Meanwhile, none of the microscopic assessment
systems demonstrated differences between different ROIs in both the glenohumeral
joint and the subacromial space. CONCLUSIONS: The macroscopic assessment system
for synovitis in rotator cuff disease in this study showed excellent reliability.
It critically described characteristics of synovitis that microscopic assessment
systems could not. Therefore, this system could be a useful tool for
investigating synovitis in rotator cuff disease.
PMID- 26423258
TI - [Drowning versus cardiac ischemia: Cardiac arrest of an 11-year-old boy at a
swimming lake].
AB - This report describes a case of sudden cardiac arrest and subsequent attempted
cardiopulmonary resuscitation of an 11-year-old child on the shores of a swimming
lake. Reports of eyewitnesses excluded the obviously suspected diagnosis of a
drowning accident. The result of the autopsy was sudden cardiac death due to a
congenital coronary anomaly (abnormal left coronary artery, ALCA). Favored by
vigorous physical activity, this anomaly can lead to malignant arrhythmias
because the ectopic coronary artery with its intramural course through the aortic
wall is compressed during every systole. This pathology was not known to the boy
or his family; in fact he liked sports but had suffered of a syncope once which
was not followed up. Without a strong suspicion it is difficult to diagnose a
coronary artery anomaly and it is often missed even in college athletes.
Tragically, sudden cardiac arrest may be the first symptom of an undiagnosed
abnormal coronary artery. Following syncope or chest pain during exercise with a
normal electrocardiogram (ECG) cardiac imaging, such as computed tomography (CT)
or angiography should be initiated in order to enable surgical repair of an
abnormal coronary artery.
PMID- 26423259
TI - Risk factors for obstetric anal sphincter injuries in twin deliveries: a
retrospective review.
AB - INTRODUCTION AND HYPOTHESIS: Risk factors for obstetric anal sphincter injuries
(OASIS) have been well-established in singleton pregnancies. Considering the
unique characteristics of twin deliveries, our aim was to identify risk factors
for OASIS that are specific to twins. METHODS: A retrospective study of all
vaginal twin deliveries in a tertiary center between 2000 and 2014. Women who
experienced OASIS (the OASIS group) were compared with those whose anal sphincter
was intact (controls). RESULTS: Overall 717 women were eligible for the study, of
whom 20 (2.8 %) experienced OASIS. Women in the OASIS group were more likely to
be nulliparous (95.0 % vs 53.7 %, p < 0.001) and were characterized by a higher
gestational age at delivery (36.1 +/- 2.5 vs 34.6 +/- 3.3, p = 0.04), a higher
birth weight for both twin A and twin B (2,507 +/- 540 g vs 2,254 +/- 525 g, p =
0.03, and 25,49 +/- 420 g vs 2,232 +/- 606 g, p = 0.004 respectively), and a
higher rate of episiotomy (40.0 % vs 14.2 %, p = 0.001), instrumental delivery
for twin A (80.0 % vs 13.5 %, p < 0.001) or twin B (80.0 % vs 18.7 %, p < 0.001),
and inter-twin delivery interval of over 30 min (20.0 % vs 7.5 %, p = 0.04). The
only factor that remained significant on multivariate analysis was instrumental
delivery: forceps delivery of twin A (OR = 8.8, 95 % CI 2.6-30.1), vacuum
extraction of twin A (OR = 9.2, 95 % CI 2.6-34.6), and forceps delivery of twin B
(OR = 15.4, 95 % CI 4.9-48.6). In women with certain combinations of risk factors
the risk of OASIS was as high as 30 %. CONCLUSION: The overall rate of OASIS in
twins is low and instrumental delivery, especially by forceps, is a risk factor.
PMID- 26423261
TI - Post-void residual urine under 150 ml does not exclude voiding dysfunction in
women.
AB - INTRODUCTION AND HYPOTHESIS: It has been claimed that post-void residual urine
(PVR) below 150 ml rules out voiding dysfunction in women with stress urinary
incontinence (SUI) and provides license to perform sling surgery. The cut-off of
150 ml seems arbitrary, not evidence-based, and so we sought to investigate the
ability of PVR < 150 ml to exclude voiding dysfunction. METHODS: We
retrospectively reviewed the charts of all patients who underwent invasive
urodynamics from 1 January 2013 to 31 December 2013. Voiding dysfunction was
diagnosed if both the invasive urodynamic and the free flow showed abnormal
results. We registered the PVR in patients with voiding dysfunction and divided
them into groups with PVR < 150 ml and PVR >= 150 ml. Patients were then analyzed
for bladder outlet obstruction and detrusor underactivity. RESULTS: Of the 205
patients undergoing invasive urodynamics in 2013, a total of 20 had voiding
dysfunction, 2 with PVR >= 150 ml. Eighteen patients had PVR < 150 ml (range 0-50
ml); 9 had bladder outlet obstruction while 7 had detrusor underactivity. Two
patients were uncategorized. Out of the 20 patients, 7 had no symptoms or
complaints indicating voiding dysfunction. CONCLUSIONS: Patients with voiding
dysfunction often have normal PVR and so PVR < 150 ml cannot exclude voiding
dysfunction. All patients should be evaluated using free flow measurements along
with PVR to obtain a reliable, objective measurement of their voiding pattern,
before anti-incontinence surgery.
PMID- 26423260
TI - Incontinence medication response relates to the female urinary microbiota.
AB - INTRODUCTION AND HYPOTHESIS: Many adult women have resident urinary bacteria
(urinary microbiome/microbiota). In adult women affected by urinary urgency
incontinence (UUI), the etiologic and/or therapeutic role of the urinary
microbiome/microbiota remains unknown. We hypothesized that microbiome/microbiota
characteristics would relate to clinically relevant treatment response to UUI
medication per os. METHODS: Adult women initiating medication treatment orally
for UUI and a comparator group of unaffected women were recruited in a tertiary
care health-care system. All participants provided baseline clinical data and
urine samples. Women with UUI were given 5 mg solifenacin, with potential dose
escalation to 10 mg for inadequate UUI symptom control at 4 weeks. Additional
data and urine samples were collected from women with UUI at 4 and 12 weeks. The
samples were assessed using 16S ribosomal RNA (rRNA) gene sequencing and enhanced
quantitative urine culturing. The primary outcome was treatment response as
measured by the validated Patient Global Symptom Control (PGSC) questionnaire.
Clinically relevant UUI symptom control was defined as a 4 or 5 score on the
PGSC. RESULTS: Diversity and composition of the urinary microbiome/microbiota of
women with and without UUI differed at baseline. Women with UUI had more bacteria
and a more diverse microbiome/microbiota. The clinical response to solifenacin in
UUI participants was related to baseline microbiome/microbiota, with responders
more likely to have fewer bacteria and a less diverse community at baseline.
Nonresponders had a more diverse community that often included bacteria not
typically found in responders. CONCLUSIONS: Knowledge of an individual's urinary
microbiome/microbiota may help refine UUI treatment. Complementary tools, DNA
sequencing, and expanded urine culture provide information about bacteria that
appear to be related to UUI incontinence status and treatment response in this
population of adult women.
PMID- 26423264
TI - Effects of a new community-based reproductive health intervention on knowledge of
and attitudes and behaviors toward stress urinary incontinence among young women
in Shanghai: a cluster-randomized controlled trial.
AB - INTRODUCTION AND HYPOTHESIS: This study aimed to evaluate the prevalence of
stress urinary incontinence (SUI) and to introduce a new community-based
reproductive health intervention. We then evaluated the effectiveness of this
intervention. METHODS: In this cluster-randomized trial, 2100 participants aged
18-40 years were divided randomly into an intervention group (IG, 1400 women) and
a control group (CG, 700 women). The CG received traditional community
intervention, cmprising limited reproductive information and education; the IG
received the new community-based reproductive health intervention model,
comprising self-designed handbooks, health lectures, and free medical
consultations, in addition to the traditional community intervention. All
participants were surveyed face to face using a self-designed questionnaire
before and after the 6-month intervention. RESULTS: In Shanghai, the prevalence
rate of SUI was 14.3 %. No difference was observed between groups regarding mean
knowledge, attitudes, and practices (KAPs) about SUI and the total score at
baseline (P > 0.05). The IG scored significantly higher than the CG on the KAP
questions at follow-up, and a significant improvement was observed in the IG
after the intervention. Total scores increased with age, educational level,
income, and time spent working in Shanghai per year but decreased with gravidity
and the number of abortions. Native respondents scored higher than did migrants.
CONCLUSIONS: The prevalence of SUI is high in Shanghai, and the new community
based reproductive health intervention model is both effective and easily
implemented. This intervention should focus on women with a low income, women
with low education levels, young women, migrant women, and women who have had
multiple abortions or pregnancies.
PMID- 26423265
TI - Digital assessment and quantification of pelvic organ prolapse (DPOP-Q): a
randomised cross-over diagnostic agreement trial.
AB - INTRODUCTION: Pelvic Organ Prolapse Quantification (POP-Q) system, measured in
centimetres using a ruler (e.g. POPstix(r)), is recommended to quantify prolapse
severity. POPstix(r) are costly (US $1/ruler). Home-made devices are used
instead, but these have not been shown to be reproducible. HYPOTHESIS: Digitally
assessed POP-Q (DPOP-Q) is as reliable, reproducible and acceptable as POP-Q
assessed using POPstix(r). METHODS: In this randomised crossover diagnostic
agreement trial, each assessor measured the index finger of their dominant hand
using a ruler. At visit one, patients were randomised to either POPstix(r) POP-Q
assessment in a modified lithotomy position or DPOP-Q in both modified a
lithotomy and a standing position. After the first clinician conducted this
assessment, a second blinded clinician then carried out the remaining assessment
on the same patient. For each examination, duration was recorded, along with a
patient-completed discomfort score. Twenty-five women were invited for visit two,
at which DPOP-Q was recorded by the same clinician who undertook DPOP-Q at the
first visit. This allowed evaluation of inter- and intraobserver agreement
together with examination acceptability. RESULTS: One hundred and nine women were
recruited [median age 55 years, parity 2, body mass index (BMI) 27.1]. Of the 25
patients invited, 23 returned for visit two. DPOP-Q had high interobserver
reliability [kappa = 0.94, 95 % confidence interval (CI) 0.878-0.996] and
intraobserver reliability (alpha = 0.96) with POPstix(r). DPOP-Q was
significantly quicker (p = 0.02) and less uncomfortable (p < 0.01) than
POPstix(r) POP-Q. CONCLUSION: DPOP-Q is reliable, acceptable and cost effective.
PMID- 26423266
TI - Design and engineering of a man-made diffusive electron-transport protein.
AB - Maquettes are man-made cofactor-binding oxidoreductases designed from first
principles with minimal reference to natural protein sequences. Here we focus on
water-soluble maquettes designed and engineered to perform diffusive electron
transport of the kind typically carried out by cytochromes, ferredoxins and
flavodoxins and other small proteins in photosynthetic and respiratory energy
conversion and oxido-reductive metabolism. Our designs were tested by analysis of
electron transfer between heme maquettes and the well-known natural electron
transporter, cytochrome c. Electron-transfer kinetics were measured from seconds
to milliseconds by stopped-flow, while sub-millisecond resolution was achieved
through laser photolysis of the carbon monoxide maquette heme complex. These
measurements demonstrate electron transfer from the maquette to cytochrome c,
reproducing the timescales and charge complementarity modulation observed in
natural systems. The ionic strength dependence of inter-protein electron transfer
from 9.7*10(6) M(-1) s(-1) to 1.2*10(9) M(-1) s(-1) follows a simple Debye-Huckel
model for attraction between +8 net charged oxidized cytochrome c and -19 net
charged heme maquette, with no indication of significant protein dipole moment
steering. Successfully recreating essential components of energy conversion and
downstream metabolism in man-made proteins holds promise for in vivo clinical
intervention and for the production of fuel or other industrial products. This
article is part of a Special Issue entitled Biodesign for Bioenergetics--the
design and engineering of electronic transfer cofactors, proteins and protein
networks, edited by Ronald L. Koder and J.L. Ross Anderson.
PMID- 26423268
TI - Simultaneous progression patterns of scoliosis, pelvic obliquity, and hip
subluxation/dislocation in non-ambulatory neuromuscular patients: an approach to
deformity documentation.
AB - BACKGROUND: A triad of deformities-thoracolumbar scoliosis, pelvic obliquity, and
femoral head (hip) subluxation/dislocation-occurs frequently in non-ambulatory
neuromuscular patients, but their close inter-relationship is infrequently
appreciated or quantified. We propose a deformity documentation approach to
assess each component simultaneously. METHODS: The documentation assesses each
component for maximal functional level, deformity, and flexibility/rigidity:
deformity from antero-posterior radiographs (scoliosis-maximal functional
position, pelvic obliquity-sitting, hip position-supine) and flexibility/rigidity
from extent of repositioning on supine (spine, pelvis) and frog lateral (hip)
radiographs. The approach was applied in 211 patients: Duchenne muscular
dystrophy (110), spinal muscular atrophy (49), cerebral palsy (26), and other
neuromuscular disorders (26). RESULTS: Measurement of 2124 radiological data
points allowed for deformity (mild to moderate to severe) and
flexibility/rigidity (fully reducible to partially to non-reducible) gradations
for scoliosis, pelvic obliquity, and hip subluxation/dislocation. The charting
documented: (1) numerical deformity and flexibility/rigidity changes [x-axis:
age; y-axis: angulation (scoliosis and pelvic obliquity) and percent coverage
(hip subluxation or dislocation) from 0-120]; and (2) grade deformity and
flexibility/rigidity changes [x-axis: age; y-axis: deformity and
flexibility/rigidity, following conversion of numerical measurements to a 1-5
grade scale]. In subgroups with the most extensive documentation, thoracolumbar
and lumbar scoliosis extended into the sacrum with 98 % (114/116) accompanied by
pelvic obliquity; and scoliosis developed more rapidly than hip deformity in 44 %
(28/63), scoliosis and hip deformity developed at the same time in 40 % (25/63),
and hip deformity developed more rapidly than scoliosis in 16 % (10/63)
(Pearson's chi-squared test p = 0.0501, almost significant). CONCLUSION AND
SIGNIFICANCE: Documentation of the triad of neuromuscular deformities is
applicable to all diagnoses; it outlines maximal functional level, deformity, and
flexibility/rigidity at each site; and it shows the relationship between spine,
pelvic, and hip deformation. Prospective charting will enhance both clinical
management and clinical research into neuromuscular deformity.
PMID- 26423267
TI - Breeding on the leading edge of a northward range expansion: differences in
morphology and the stress response in the arctic Gambel's white-crowned sparrow.
AB - Individuals at the forefront of a range shift are likely to exhibit phenotypic
traits that distinguish them from the population breeding within the historic
range. Recent studies have examined morphological, physiological and behavioral
phenotypes of individuals at the edge of their range. Several studies have found
differences in the hypothalamic-pituitary-adrenal (HPA) axis activity in response
to acute restraint stress in individuals at the range limits. HPA axis activation
leads to elevations in glucocorticoids that regulate physiology and behavior.
Here we compare the hormonal profiles and morphometrics from Gambel's white
crowned sparrows (Zonotrichia leucophrys gambelii) breeding at the northern limit
of the population's range to those birds breeding within the historic population
range. Birds breeding at the northern limit experienced a harsher environment
with colder temperatures; however, we found no differences in arthropod prey
biomass between the northern limit and more southern (historic) sites. Males at
the northern limit had higher body condition scores (mass corrected for body
size) compared to individuals within the historic range, but no differences were
found in beak and tarsus lengths, wing chord, muscle profile or fat stores. In
males during the pre-parental stage, before breeding commenced, HPA axis activity
was elevated in birds at the northern limit of the range, but no differences were
found during the parental or molt stages. Females showed no differences in HPA
axis activity during the parental stage. This study suggests that "pioneering"
individuals at the limits of their breeding range exhibit physiology and
morphology that are distinct from individuals within the historic range.
PMID- 26423269
TI - Proximal subscapularis release for the treatment of adduction-internal rotation
shoulder contracture in obstetric brachial plexus palsy.
AB - INTRODUCTION: The purpose of this paper was to evaluate the results on shoulder
function following isolated proximal subscapularis release in children with Erb's
palsy. METHODS: A retrospective study was conducted on 64 consecutive children
with Erb's palsy who underwent a Carlioz proximal subscapularis release between
2001 and 2012. Fifty children with complete records and a minimum follow-up of 2
years were included for evaluation. Age at surgery ranged from 1.3 to 4.5 years
(average 2.6 years). Preoperative active shoulder abduction/anterior elevation,
active external and internal rotations as well as the Mallet score were compared
with those found at 6 and 24 months postoperatively using the Student paired t
test, with a confidence interval of 95 %. The results were compared between
children <3 years of age at surgery and those older, and between children who had
an isolated C5-C6 and those with greater involvement. p < 0.05 was considered
statistically significant. RESULTS: Active abduction improved 21 degrees at 6
months and 31 degrees (total) at 2 years (p < 0.01) with an overall Mallet
abduction score improvement of 0.58 at 6 months and 0.6 (overall) at 2 years (p <
0.01). Active external rotation improved 52 degrees at 6 months and 35 degrees
(total) at 2 years (p < 0.01) with an overall Mallet external rotation score
improvement of 1.3 at 6 months (p < 0.01) and 0.52 (overall) at 2 years (p =
0.013). There was no statistically significant change in internal rotation (p =
0.37). We found no correlation between the child's age or the severity of
involvement at surgery and the end result. CONCLUSION: Proximal subscapularis
release according to Carlioz is simple and effective in improving overall
shoulder function in children with obstetric brachial plexus palsy, mainly
abduction and external rotation. Improvement tends to reach a plateau around 6-12
months postoperatively.
PMID- 26423270
TI - Percutaneous epiphysiodesis using transphyseal screws for limb-length
discrepancies: high variability among growth predictor models.
AB - PURPOSE: Percutaneous epiphysiodesis using transphyseal screws (PETS) was
developed as a minimally invasive outpatient procedure to address limb-length
discrepancy (LLD) that allowed immediate postoperative weight bearing and was
potentially reversible by removing the screws. The aims of our study were to
report our results using PETS for LLD and evaluate the accuracy of three growth
predictor models. METHODS: Sixteen patients with an average age of 14 years were
treated for LLD using PETS. Thirteen patients had screws inserted in a parallel
fashion and 3 had crossed screws. We compared the predicted LLD at skeletal
maturity using the three growth predictor methods with the actual LLD at skeletal
maturity and preoperative LLD with the final LLD at skeletal maturity. RESULTS:
The mean LLD at skeletal maturity between the predicted and final measurements
was 0.2 cm using the Green-Anderson method, 1.4 cm using the Moseley method, and
0.1 cm using the Paley method. The mean preoperative LLD of 3.1 cm was corrected
to 1.7 cm at skeletal maturity (p < 0.001). Six patients complained of pain over
the screw heads; however, no patient developed an infection or angular deformity.
CONCLUSIONS: The three growth predictor methods predicted the final LLD within an
average of 1.4 cm, but there was high variability. Although PETS improved the LLD
by a mean of 1.4 cm, we believe the results would have been better if PETS was
performed at an earlier skeletal age.
PMID- 26423271
TI - Effects of training on LV strain in competitive athletes.
AB - OBJECTIVE: LV longitudinal strain, a recognised marker of LV function, has been
recently applied to the evaluation of the athlete's heart. At present, little is
known about the influence of training on LV global longitudinal strain (GLS) in
athletes. The aim of this study was to prospectively investigate the impact of
training on LV longitudinal strain and twist mechanics in a cohort of competitive
athletes. METHODS: Ninety-one competitive athletes, practising team sports and
competing at national or international level, were analysed. Echocardiographic
evaluation was performed at the beginning of the season (low training) and after
18+/-2 weeks of a supervised, intensive training programme (peak training).
RESULTS: A significant increase in LV mass (p<0.0001), LV end-diastolic and end
systolic volume (p=0.0001 and <0.0001, respectively) was found at peak training.
LV basal and apical torsion (p=0.59 and 0.43, respectively) and LV twisting
(p=0.78) did not change, and only a mild increase in LV GLS was evident after
training (p=0.044). Resting heart rate was identified as the only independent
predictor of LV GLS after training (beta=0.30, p=0.005). CONCLUSIONS: A 18-week,
intensive training programme induced only a slight increase in LV GLS despite
marked changes in cardiac morphology, suggesting a physiological adaptation of
the LV to exercise conditioning.
PMID- 26423272
TI - Pharmacotherapy to Enhance Cognitive and Motor Recovery Following Stroke.
AB - Stroke is a leading cause of disability among older adults and more than half of
stroke survivors have some residual neurological impairment. Traditionally,
managing the aftermath of stroke has been by the implementation of several
physical and language therapy modalities. The limitations of these rehabilitation
efforts have sparked an interest in finding other ways to enhance neurological
recovery. Some of these novel approaches have included pharmacological
interventions, cell-derived treatments, and cortical magnetic stimulation.
Mounting evidence over the last 2 decades suggests that pharmacological
manipulations may have the potential to modulate practice-dependent
neuroplasticity and potentially improve neurological recovery after stroke.
Multiple pharmacological agents with different mechanisms of action have been
evaluated, showing conflicting results. Some studies suggest some promise, yet
the quality of the available studies is suboptimal overall, with most of the
studies being underpowered. So far, the most promising agents include the
antidepressants for motor recovery and acetylcholinesterase inhibitors and
memantine for aphasia. However, large, well-designed clinical trials are needed
to address the shortcomings of the available data and before any pharmacological
agent can be recommended for routine use as part of the standard algorithm of
stroke management.
PMID- 26423273
TI - Inadvertent ligation of the left pulmonary artery during intended ductal
ligation.
AB - BACKGROUND: Inadvertent ligation of the left pulmonary artery during attempted
surgical closure of a Patent Ductus Arteriosus has long been recognized as one of
the less common complications of this procedure. Surgical reconstruction of the
left pulmonary artery was then often attempted but was difficult or impossible in
some of the patients with hypoplasia of the left pulmonary artery and the left
lung. CASE PRESENTATION: A 10-year-old girl presented with marked exercise
intolerance and palpitations and was diagnosed to have large PDA. She had feeding
difficulty, diaphoresis, failure to gain weight, recurrent chest infections
during infancy and early childhood. Physical examination revealed an underweight
child with wide pulse pressure and bounding peripheral pulses. She had active
precordium with accentuated P2 and machinery murmur in the left 2nd intercostal
space and mid diastolic rumble at the mitral area. Echocardiography showed a 12
mm patent arterial duct. She was taken for an intended surgical ligation of the
duct but a control echocardiogram on the 3rd postoperative day revealed that the
left pulmonary artery, instead of the duct, was ligated. Surgical reconstruction
of the left pulmonary artery was undertaken 3 years later, however, this was
complicated by post reconstruction left pulmonary artery stenosis. Successful
percutaneous stenting of the left pulmonary artery was performed 18 months after
the surgical reconstruction. CONCLUSION: The incidence of inadvertent LPA
ligation may be underestimated where PDA ligation is done by less experienced
surgeons and postoperative echocardiography is not routinely performed. Late
correction of inadvertent LPA ligation is an important surgical challenge,
especially if the duct is still patent. Percutaneous stenting as a primary option
may carry significant risk, as the ligated pulmonary artery is fragile. In our
case, a good result was achieved with surgical repair followed by percutaneous
stenting.
PMID- 26423275
TI - Recognising the role of primary care in cancer control.
PMID- 26423274
TI - AMBRA1 and SQSTM1 expression pattern in prostate cancer.
AB - Prostate cancer is among the most commonly diagnosed male diseases and a leading
cause of cancer mortality in men. There is emerging evidence that autophagy plays
an important role in malignant cell survival and offers protection from the anti
cancer drugs in prostate cancer cells. AMBRA1 and the autophagic protein
sequestosome-1 (SQSTM1; p62) expression were evaluated by immunohistochemistry
and western blot on tissue samples from both benign and malignant prostatic
lesions. The data reported in this pilot study demonstrated an increased
expression of AMBRA1 and SQSTM1, which were also associated with an accumulation
of LC3II in prostate cancer but not in benign lesion. In the present study we
found that: (i) at variance with benign lesion, prostate cancer cells underwent
SQSTM1 accumulation, i.e., clearly displayed a defective autophagic process but,
also, (ii) prostate cancer accumulated AMBRA1 and (iii) this increase positively
correlated with the Gleason score. These results underscore a possible
implication of autophagy in prostate cancer phenotype and of AMBRA1 as possible
cancer progression biomarker in this malignancy.
PMID- 26423276
TI - T1-hyperintense renal lesions: can high signal predict lack of enhancement?
AB - OBJECTIVE: To establish highly specific criteria for predicting non-enhancement
in T1-hyperintense non-fat-containing (T1-high) renal lesions using unenhanced
fat-suppressed T1-weighted (T1-FS) images. MATERIALS AND METHODS: This IRB
approved, HIPAA-compliant, retrospective study included T1-high renal lesions
found between 7/1/2012 and 7/1/2014. The largest lesion diameter and
heterogeneity, mean signal intensity of lesion, and adjacent renal cortex were
recorded from T1-FS images. The presence/absence of lesion enhancement was
determined from subtraction images. T1 signal ratio (T1-SR) was calculated as
(mean SI of lesion)/(mean SI of cortex). Logistic regression with binary outcome
of the presence or absence of lesion enhancement was performed. Cut-off T1-SR to
maximize specificity was established from receiver operator curve analysis.
RESULTS: There were 101 patients (58 [57.4%] male) with non-enhancing lesions and
80 patients (51 [63.8%] male) with enhancing lesions, mean ages 64.0 +/- 13.3 and
62.1 +/- 13.8 years, respectively. Median sizes were 11 mm (IQR 8-16) and 20.5 mm
(IQR 15-29) for non-enhancing and enhancing lesions, respectively (p < 0.0001).
19/101 (18.8%) of non-enhancing and 56/80 (70.0%) of enhancing lesions were
heterogeneous (p < 0.0001). T1-SR was 1.77 +/- 0.6 and 1.25 +/- 0.42 for non
enhancing and enhancing lesions, respectively (p < 0.0001). For each increase of
0.5 in T1-SR, odds ratio for non-enhancement was 3.3 (95% CI 1.85-5.79), adjusted
for lesion size and heterogeneity. T1-SR alone had area under the curve of 0.88
(95% CI 0.78-10.89) for non-enhancement. T1-SR >= 2.15 had positive likelihood
ratio of 9.5 for non-enhancement. CONCLUSION: Signal ratio of lesion to cortex >=
2.15 on unenhanced T1-weighted images is a highly specific predictor for non
enhancement.
PMID- 26423277
TI - Assessment of Directly Observed Therapy (DOT) following tuberculosis regimen
change in Addis Ababa, Ethiopia: a qualitative study.
AB - BACKGROUND: Tuberculosis remains a major public health problem in Ethiopia. In
2010 the TB treatment regimen was shortened from 8 to 6-months treatment. With
this new regimen, the full course of treatment should be taken under Directly
Observed Therapy (DOT) unlike the 8-month regimen where TB patients were only
observed during the intensive phase, this has not been tried before and may be
difficult to implement. Therefore this study aimed to investigate the experiences
from both TB patients and health care providers' perspective of implementing DOT
for the full course of TB treatment. METHODS: Qualitative study consisted of 11
in-depth interviews and 4 Focus Group Discussions (FDGs) were conducted between
March and April, 2014. Overall, 18 TB patients and 16 HCPs were involved from
three selected public health facilities (2 Health Centers and 1 Hospital) in
Addis Ababa, Ethiopia. Qualitative data analysis software (Open Code Version 3.5)
was employed to identify the key issues from these interviews through coding,
categorization and grouping into emergent themes. RESULTS: Participants reported
that making a daily visit to health facilities for DOT was difficult due to the
distance of the facilities from their residences, lack of or high transportation
cost and had undesired implications on their work and social lives. TB patients
had to overcome many challenges to comply with TB treatment on a daily basis.
HCPs also indicated the difficulties of implementing facility based daily DOT
mainly due the implication it had on their TB patients and stated DOT had not
always been implemented for the full course as recommended. HCPs also shared deep
concern regarding the risk of acquiring multiple drug resistant TB. CONCLUSION:
This study indicated there are several challenges associated with facility based
daily DOT as a method of TB treatment supervision in public health facilities in
Addis Ababa. This may be indicative of the situation in other health facilities
in Addis Ababa as well as elsewhere in the country. Hence the TB control program
has to explore how best to improve TB treatment delivery options to ensure
adequate treatment. A more patient-centered approach could be strengthened by
further decentralizing the DOT to the community level in order to ensure
adherence of patients to their TB treatment.
PMID- 26423278
TI - Evaluating the ameliorative efficacy of Spirulina platensis on spermatogenesis
and steroidogenesis in cadmium-intoxicated rats.
AB - The present study was conducted to evaluate the ameliorative efficacy of
Spirulina platensis (SP) on reproductive dysfunctions induced by cadmium chloride
(CdCl2) in male rats. Rats (n = 40) were divided into five groups (eight
rats/each). Group 1: served as control without any treatment. Group 2: Rats were
administered SP (150 mg/kg body weight (BW)) in drinking water for 10 days. Group
3: Rats were subcutaneously injected with CdCl2 (2 mg/kg BW) daily for 10 days.
Group 4: Rats were co-treated with both CdCl2 (2 mg/kg BW) and SP (150 mg/kg BW)
daily for 10 days (SP prophylactic group). Group 5: Rats received CdCl2 for 10
days followed by administration of SP alone in drinking water daily for another
30 days with the same mentioned routes and doses (SP treatment group). From our
findings, the administration of SP alone or co-administration with Cd
significantly attenuated the harmful effects of Cd, suggesting its beneficial
role in improving spermatogenesis and steroidogenesis after Cd exposure.
PMID- 26423279
TI - Thiosulphate conversion in a methane and acetate fed membrane bioreactor.
AB - The use of methane and acetate as electron donors for biological reduction of
thiosulphate in a 5-L laboratory membrane bioreactor was studied and compared to
disproportionation of thiosulphate as competing biological reaction. The reactor
was operated for 454 days in semi-batch mode; 30 % of its liquid phase was
removed and periodically replenished (days 77, 119, 166, 258, 312 and 385).
Although the reactor was operated under conditions favourable to promote
thiosulphate reduction coupled to methane oxidation, thiosulphate
disproportionation was the dominant microbial process. Pyrosequencing analysis
showed that the most abundant microorganisms in the bioreactor were phototrophic
green sulphur bacteria (GSB) belonging to the family Chlorobiaceae and
thiosulphate-disproportionating bacteria belonging to the genus Desulfocapsa.
Even though the reactor system was surrounded with opaque plastic capable of
filtering most of the light, the GSB used it to oxidize the hydrogen sulphide
produced from thiosulphate disproportionation to elemental sulphur. Interrupting
methane and acetate supply did not have any effect on the microbial processes
taking place. The ultimate goal of our research was to develop a process that
could be applied for thiosulphate and sulphate removal and biogenic sulphide
formation for metal precipitation. Even though the system achieved in this study
did not accomplish the targeted conversion using methane as electron donor, it
does perform microbial conversions which allow to directly obtain elemental
sulphur from thiosulphate.
PMID- 26423280
TI - Proteomic changes in Corbicula fluminea exposed to wastewater from a psychiatric
hospital.
AB - The increase use of pharmaceutical compounds in veterinary practice and human
population results in the ubiquitous presence of these compounds in aquatic
ecosystems. Because pharmaceuticals are highly bioactive, there is concern about
their toxicological effects in aquatic organisms. Therefore, the aim of this
study was to assess the effects of an effluent from a psychiatric hospital
(containing a complex mixture of 25 pharmaceutical compounds from eleven
therapeutic classes) on the freshwater clam Corbicula fluminea using a proteomic
approach. The exposure of C. fluminea to this complex effluent containing
anxiolytics, analgesics, lipid regulators, beta blockers, antidepressants,
antiepileptics, antihistamines, antihypertensives, antiplatelets and
antiarrhythmics induced protein changes after 1 day of exposure in clam gills and
digestive gland more evident in the digestive gland. These changes included
increase in the abundance of proteins associated with structural (actin and
tubulin), cellular functions (calreticulin, proliferating cell nuclear antigen
(PCNA), T complex protein 1 (TCP1)) and metabolism (aldehyde dehydrogenase
(ALDH), alcohol dehydrogenase, 6 phosphogluconate dehydrogenase). Results from
this study indicate that calreticulin, PCNA, ALDH and alcohol dehydrogenase in
the digestive gland and T complex protein 1 (TCP1)) and 6 phosphogluconate
dehydrogenase in the gills represent useful biomarkers for the ecotoxicological
characterization of psychiatric hospital effluents in this species.
PMID- 26423281
TI - Environmental risks of HBCDD from construction and demolition waste: a
contemporary and future issue.
AB - Hexabromocyclododecane (HBCDD), as one of the most widely used brominated flame
retardants (BFRs), is of great concern globally because of its persistence in the
environment and negative impacts on humans and animals. HBCDD has been mainly
used in flame-retarded expanded (EPS) and extruded (XPS) polystyrene foams for
insulation in the construction industry. Most of these products will become a
part of the construction and demolition (C&D) waste at the end of their life
cycle (30-50 years) which is typically disposed of into landfills or
incineration. However, the recycling of this material takes quite a low share
compared with landfill and incineration. Consequently, high environmental risks
will exist in these disposal approaches due to the HBCDD in C&D waste. Currently,
XPS or EPS products containing HBCDD in the construction industry have not
reached the end of their life cycle in most countries. Relatively little
attention has been paid to this emergency issue by either the government or
public. Furthermore, C&D waste is most likely disposed of by direct dumping,
simple stacking, or open burning in developing countries. Therefore, this paper
highlights the global environmental risks of HBCDD from C&D waste. Areas of
research for key problems of HBCDD contained in C&D waste are suggested to help
control and finally eliminate the impact.
PMID- 26423282
TI - Cadmium exposure and risk of pancreatic cancer: a meta-analysis of prospective
cohort studies and case-control studies among individuals without occupational
exposure history.
AB - Pancreatic cancer is one of the most deadly types of cancer for both genders.
Classified as a human carcinogen, cadmium has been related to diverse cancers.
However, the association between cadmium exposure and the risk of pancreatic
cancer is still unclear. We quantitatively reviewed the observational studies on
the association of cadmium exposure with pancreatic cancer risk among individuals
without occupational exposure history published through July 2014 in PubMed by
using a fixed-effect model. Four prospective cohort studies (112,934 participants
with 335 events) and two case-control studies (177 cases and 539 controls) were
identified. The summarized relative risk (RR) with a 95% confidence interval (CI)
was 2.05 (95% CI = 1.58-2.66), comparing the highest to the lowest category of
cadmium exposure. This positive association persisted in men (RR = 1.78, 95% CI =
1.04-3.05) but not in women (RR = 1.02, 95% CI = 0.63-1.65). Further research is
needed to provide more solid evidence on the association of cadmium exposure with
pancreatic cancer risk and to elucidate the underlying biological mechanism of
the potential gender difference.
PMID- 26423283
TI - Improving the efficiency of phytoremediation using electrically charged plant and
chelating agents.
AB - The low efficiency of phytoremediation is a considerable problem that limits the
application of this environmentally friendly method on heavy metal-polluted
soils. The combination of chelate-assisted phytoextraction and electrokinetic
remediation could offer new opportunities to improve the effectiveness of
phytoextraction. The current experiment aims to investigate the effects of
electrical fields and chelating agents on phytoremediation efficiency. In a pot
experiment using mine soil, poultry manure extract (PME), cow manure extract
(CME), and ethylenediaminetetraacetic acid (EDTA) were applied to soil as
chelating agents (2 g kg(-1)) at the beginning of the flowering stage. A week
later, Helianthus annuus (sunflower) was negatively charged by inserting a
stainless steel needle with 10 and 30 V DC electricity in the lowest part of the
stems for 1 h each day for a 14-day period. At the end of the experiment, the
shoot and root dry weight, lead (Pb) concentration in plant organs, translocation
factor (TF), metal uptake index (UI), and soil available Pb (diethylene triamine
pentaacetic acid (DTPA) extractable) were detected. Results indicated that the
application of electrical fields had no significant impact on the shoot and root
dry weights, while Pb concentration and UI increased in the 10-V EDTA treatment
by 500 % compared to control. There was no significant difference between UI in
30- and 10-V EDTA treatments. Soil available Pb significantly increased in the 30
V treated soil. A positive correlation was observed between the available Pb in
soil near the root and Pb concentration in shoot, its TF, and UI. In conclusion,
a negatively charged plant along with the application of EDTA significantly
increased the phytoremediation efficiency.
PMID- 26423284
TI - Influence of environmental factors on the phosphorus adsorption of lanthanum
modified bentonite in eutrophic water and sediment.
AB - Lanthanum-modified bentonite has potential for wide application in eutrophication
control. We investigated P adsorption on a lanthanum-modified bentonite by
analysis of adsorption kinetics, equilibrium, and the effect of environmental
factors. P adsorption closely followed the pseudo-second-order kinetic model, and
the isotherm was well described by the Langmuir model. This adsorbent could
effectively immobilize P into the sediment, but the adsorption process was
strongly dependent on pH, anions, and low molecular weight organic acids
(LMWOAs). P adsorption increased with increasing pH from 0.52 mg P/g at pH 3.0 to
0.93 mg P/g at pH 7.0 with no adsorption at pH 11. P adsorption was strongly
inhibited in the presence of anions and three LMWOAs, with P even re-released at
high concentrations. These environmental factors should be given significant
attention when considering the application of lanthanum-modified bentonite in
eutrophication control.
PMID- 26423285
TI - Effects of electromagnetic fields on serum lipids in workers of a power plant.
AB - This study aimed to evaluate the effects of electromagnetic fields (EMF) exposure
on levels of serum lipids in workers of an electric power plant. A cross
sectional study was carried out in an electric power plant in Zhejiang province,
China, from August to September 2011. All participants were divided into two
groups with high occupational EMF exposure and low occupational EMF exposure. The
occupational EMF exposure included radiofrequency EMF and extremely low-frequency
EMF. Occupational EMF exposure was associated with an increased level of low
density lipoprotein cholesterol (LDL-c; beta = 0.17 mmol/L, P = 0.022). High EMF
exposure group with longer employment duration, longer daily EMF exposure
duration, and more mobile phone or electric fee per month had significantly
higher levels of total cholesterol, LDL-c, or triglyceride than the corresponding
reference group. However, significantly decreased level of high-density
lipoprotein cholesterol was only observed in high EMF exposure group with more
mobile phone fee per month. Similar results were also found in 544 participants
with available data of serum lipids in 2010. The findings showed that chronic EMF
exposure was associated with the change of serum lipid levels. EMF exposure might
modulate the process of lipid metabolism.
PMID- 26423286
TI - Endogenous mitigation of H2S inside of the landfills.
AB - Vast quantities of hydrogen sulfide (H2S) emitted from landfill sites require
urgent disposal. The current study focused on source control and examined the
migration and conversion behavior of sulfur compounds in two lab-scale simulated
landfills with different operation modes. It aimed to explore the possible
strategies and mechanisms for H2S endogenous mitigation inside of landfills
during decomposition. It was found that the strength of H2S emissions from the
landfill sites was dependent on the municipal solid waste (MSW) degradation speed
and vertical distribution of sulfide. Leachate recirculation can shorten both the
H2S influence period and pollution risk to the surrounding environment. H2S
endogenous mitigation may be achieved by chemical oxidation, biological
oxidation, adsorption, and/or precipitation in different stages. Migration and
conversion mainly affected H2S release behavior during the initial stabilization
phase in the landfill. Microbial activities related to sulfur, nitrogen, and iron
can further promote H2S endogenous mitigation during the high reducing phase.
Thus, H2S endogenous mitigation can be effectively enhanced via control of the
aforementioned processes.
PMID- 26423287
TI - Retention and efficacy of ultra-low volume pesticide applications on Culex
quinquefasciatus (Diptera: Culicidae).
AB - To combat mosquitoes and the public health hazards they present, spraying
chemical adulticides is an efficient and timely control method for immediate
reduction of adult populations. With the growing consciousness of environmental
and public health concerns, effective mosquito control means not only maximizing
the effectiveness (in terms of mosquito mortality rates) of the pesticide
application, but also minimizing the unintended effects (health hazard and
environmental pollution). A series of experiments was carried out to assess the
efficacy and deposition of ultra-low volume (ULV) sprays on adult mosquitoes
which included the influence of chemical type, spray volume, spray concentration,
droplet size, and deposit location (where the droplets land on the mosquito). A
modified Potter Tower was used to apply an extremely fine spray (volume median
diameter ~20 MUm) on caged adult mosquitoes (Culex quinquefasciatus). Reslin (50
g/L bioresmethrin) was diluted in either water or D-C-Tron plus spray oil (782
g/L paraffinic petroleum oil), Twilight (89 g/L phenothrin) was diluted in D-C
Tron, and the mosquito mortality was assessed 24 h after spraying. A fluorescent
tracer was added to the spray mixture to determine the amount of spray on
mosquitoes. A fluorescent microscope was also used to view the deposit of
droplets on mosquitoes. It was found that droplet retention and mortality were
reduced with the larger droplet sizes. Large water-based droplets tend to bounce
off adult mosquitoes. There is a tendency for droplets approximately 20 MUm in
size to be retained on the fine hairs on the mosquito. The largest spray deposit
was found on the adult mosquito wings and the lowest deposit on the head.
Mortality was higher for formulations diluted with oil compared to those diluted
with water. ULV applications with ultra-fine sprays (VMD 20 MUm) and oil-based
products resulted in maximum target efficacy under laboratory conditions, at
minimum cost, and with the minimum amount of chemical adulticides.
PMID- 26423288
TI - Biomonitoring of agricultural workers exposed to pesticide mixtures in Guerrero
state, Mexico, with comet assay and micronucleus test.
AB - The aim of this study was to evaluate the genotoxic effect of pesticides in
exfoliated buccal cells of workers occupationally exposed in Guerrero, Mexico,
using the comet assay and the micronucleus test. The study compared 111
agricultural workers in three rural communities (Arcelia 62, Ajuchitlan 13, and
Tlapehuala 36), with 60 non-exposed individuals. All the participants were males.
The presence of DNA damage was investigated in the exfoliated buccal cells of
study participants with the comet assay and the micronucleus (MN) test; comet
tail length was evaluated in 100 nuclei and 3000 epithelial cells of each
individual, respectively; other nuclear anomalies such as nuclear buds,
karyolysis, karyorrhexis, and binucleate cells were also evaluated. Study results
revealed that the tail migration of DNA and the frequency of MN increased
significantly in the exposed group, which also showed nuclear anomalies
associated with cytotoxic or genotoxic effect. No positive correlation was noted
between exposure time and tail length and micronuclei frequencies. No significant
effect on genetic damage was observed as a result of age, smoking, and alcohol
consumption. The MN and comet assay in exfoliated buccal cells are useful and
minimally invasive methods for monitoring genetic damage in individuals exposed
to pesticides. This study provided valuable data for establishing the possible
risk to human health associated with pesticide exposure.
PMID- 26423289
TI - Ecotoxicological effects of sediments from Mar Piccolo, South Italy: toxicity
testing with organisms from different trophic levels.
AB - The Mar Piccolo of Taranto (Ionian Sea, Southern Italy) is a semi-enclosed and
strongly polluted basin. For decades, it has been subjected to different
anthropogenic impacts. These stressors caused severe sediments contamination with
high concentration of different pollutants (PAHs, PCB, heavy metals). In order to
assess the current status of sediments contamination, an ecotoxicological
investigation combined with chemical analysis (heavy metals, PAH, and PCB) has
been performed. In order to derive ecologically relevant conclusions, a
multiorganisms and multiend-points approach has been applied, exposing organisms
from different trophic levels to elutriate and whole sediment. The battery of
bioassays consists of a microalgal growth inhibition test (Dunaliella
tertiolecta), acute and sublethal assays (end-points: mortality, immobilization
and swimming speed alteration) on crustaceans larvae and juveniles, and rotifers
(Amphibalanus amphitrite, Artemia salina, Corophium insidiosum and Brachionus
plicatilis), and embryotoxicity test on echinoderms (Paracentrotus lividus).
Considering the high levels of sediment contamination highlighted from chemical
analysis, an unexpected very low toxic effect was observed, even considering the
sublethal end-point (larval swimming speed alteration). The results of this study
suggest a very complex contaminants dynamic in the Mar Piccolo sediments that,
despite a strong level of contamination, seems to not affect in a proportional
manner the biological compartment.
PMID- 26423290
TI - Effect of arbuscular mycorrhizal and bacterial inocula on nitrate concentration
in mesocosms simulating a wastewater treatment system relying on phytodepuration.
AB - High nitrogen concentration in wastewaters requires treatments to prevent the
risks of eutrophication in rivers, lakes and coastal waters. The use of
constructed wetlands is one of the possible approaches to lower nitrate
concentration in wastewaters. Beyond supporting the growth of the bacteria
operating denitrification, plants can directly take up nitrogen. Since plant
roots interact with a number of soil microorganisms, in the present work we
report the monitoring of nitrate concentration in macrocosms with four different
levels of added nitrate (0, 30, 60 and 90 mg l(-1)), using Phragmites australis,
inoculated with bacteria or arbuscular mycorrhizal fungi, to assess whether the
use of such inocula could improve wastewater denitrification. Higher potassium
nitrate concentration increased plant growth and inoculation with arbuscular
mycorrhizal fungi or bacteria resulted in larger plants with more developed root
systems. In the case of plants inoculated with arbuscular mycorrhizal fungi, a
faster decrease of nitrate concentration was observed, while the N%/C% ratio of
the plants of the different treatments remained similar. At 90 mg l(-1) of added
nitrate, only mycorrhizal plants were able to decrease nitrate concentration to
the limits prescribed by the Italian law. These data suggest that mycorrhizal and
microbial inoculation can be an additional tool to improve the efficiency of
denitrification in the treatment of wastewaters via constructed wetlands.
PMID- 26423291
TI - Aqueous chlorination of acebutolol: kinetics, transformation by-products, and
mechanism.
AB - This study investigated the reaction kinetics and the transformation by-products
of acebutolol during aqueous chlorination. Acebutolol is one of the commonly used
beta-blockers for the treatment of cardiovascular diseases. It has been
frequently detected in the aquatic environment. In the kinetics study, the second
order rate constant for the reaction between acebutolol and chlorine (k app) was
determined at 25 +/- 0.1 degrees C. The degradation of acebutolol by free
available chlorine was highly pH dependence. When the pH increased from 6 to 8,
it was found that the k app for the reaction between acebutolol and free
available chlorine was increased from 1.68 to 11.2 M(-1) min(-1). By comparing
with the reported k app values, the reactivity of acebutolol toward free
available chlorine was found to be higher than atenolol and metoprolol but lower
than nadolol and propranolol. Characterization of the transformation by-products
formed during the chlorination of acebutolol was carried out using liquid
chromatography-quadrupole time-of-flight high-resolution mass spectrometry. Seven
major transformation by-products were identified. These transformation by
products were mainly formed through dealkylation, hydroxylation, chlorination,
and oxidation reactions.
PMID- 26423292
TI - Study of CO2 cyclic absorption stability of CaO-based sorbents derived from lime
mud purified by sucrose method.
AB - Using lime mud (LM) purified by sucrose method, derived from paper-making
industry, as calcium precursor, and using mineral rejects-bauxite-tailings (BTs)
from aluminum production as dopant, the CaO-based sorbents for high-temperature
CO2 capture were prepared. Effects of BTs content, precalcining time, and
temperature on CO2 cyclic absorption stability were illustrated. The cyclic
carbonation behavior was investigated in a thermogravimetric analyzer (TGA).
Phase composition and morphologies were analyzed by XRD and SEM. The results
reflected that the as-synthesized CaO-based sorbent doped with 10 wt% BTs showed
a superior CO2 cyclic absorption-desorption conversion during multiple cycles,
with conversion being >38 % after 50 cycles. Occurrence of Ca12Al14O33 phase
during precalcination was probably responsible for the excellent CO2 cyclic
stability.
PMID- 26423293
TI - Comparing systematic reviews and meta-analyses of randomized clinical trials with
cohort studies: a paradigm of single-incision laparoscopic surgery.
PMID- 26423294
TI - Traumatic lumbar hernia repair: experience at the Royal Brisbane and Women's
Hospital.
AB - BACKGROUND: Traumatic lumbar hernias (TLH) are a rare clinical entity with fewer
than 100 cases reported in the English literature worldwide. Due to the
surrounding anatomy, surgical repair is often difficult. There is currently no
consensus on the timing of operative repair of TLH. The aim of this study is to
present a case series on the management of TLH performed at the Royal Brisbane
and Women's Hospital (RBWH) utilizing both open and laparoscopic techniques with
both early and delayed repairs being undertaken. METHODS: Cases were identified
retrospectively from the Trauma Database at the RBWH, a tertiary-level hospital
in Brisbane, Australia. RESULTS: Four cases of TLH were identified from 2009 to
2014. The diagnosis was confirmed pre-operatively on CT imaging. Early repair was
undertaken when the patient was stable from other associated injuries. Herniation
was managed in three cases by open repair (2x open lumbar approaches, 1 via
midline laparotomy) with sublay extraperitoneal mesh placement. The remaining
case was managed by laparoscopic extra-peritoneal mesh repair. At a minimal 4
months follow-up, no evidence of recurrence or complications was detected in
three cases. One patient was lost to follow-up. CONCLUSIONS: TLH are a rare
clinical entity. Operative management can be achieved via open or laparoscopic
techniques, with placement of mesh in the extraperitoneal plane. Both early, when
the patients clinical status allows, and delayed repair appear to have good short
term results. Long-term data are not available at this stage.
PMID- 26423295
TI - The Use of Mathematical Modelling for Improving the Tissue Engineering of Organs
and Stem Cell Therapy.
AB - Regenerative medicine is a multidisciplinary field where continued progress
relies on the incorporation of a diverse set of technologies from a wide range of
disciplines within medicine, science and engineering. This review describes how
one such technique, mathematical modelling, can be utilised to improve the tissue
engineering of organs and stem cell therapy. Several case studies, taken from
research carried out by our group, ACTREM, demonstrate the utility of mechanistic
mathematical models to help aid the design and optimisation of protocols in
regenerative medicine.
PMID- 26423297
TI - Telocytes as a Source of Progenitor Cells in Regeneration and Repair Through
Granulation Tissue.
AB - This review outlines the role of CD34+ stromal cells/telocytes (CD34+ SC/TCs) in
repair and considers the following issues. Firstly, the conceptual aspects of
repair, including regeneration and repair through granulation tissue (RTGT) as
two types of repair, RTGT stages (inflammatory, proliferative, and remodeling),
and tissue in repair as a substrate to assess the in vivo behavior of activated
CD34+ SC/TCs. Subsequently, current knowledge of CD34+ SC/TCs, such as
identification, characteristics, and functions, as well as possible stages
(quiescent and activated) are taken into account. We then consider the role in
regeneration of quiescent CD34+ SC/TCs (in unperturbed physiological conditions)
as a nurse of stem cells (e.g., in the heart, skin, respiratory tree,
gastrointestinal tract, liver, eye, and choroid plexus). Special attention is
paid to the characteristics of activated CD34+ SC/TCs and the overlapping steps
of activation with and without loss of CD34 expression and with and without gain
of alphaSMA expression. With this contribution, we establish the role of CD34+
SC/TCs as progenitor cells and as a source of fibroblasts and myofibroblasts in
repair through granulation tissue, fibrosis, and tumor stroma. Activated CD34+
SC/TCs in encapsulation and other processes (e.g., Reinke's edema, cutaneous
myxoid cyst, mixomatous mitral valve degeneration, and fibrous papula of the
face) are also outlined. Finally, similarities between modifications of CD34+
SC/TCs during in vivo activation and of multipotent mesenchymal stromal/stem
cells in culture are examined in order to correlate the growing literature on
CD34+ SC/TCs and the exponential research in cultured mesenchymal stromal/stem
cells.
PMID- 26423298
TI - Filling the Gaps between the In Vivo and In Vitro Microenvironment: Engineering
of Spheroids for Stem Cell Technology.
AB - Engineering of in vitro three-dimensional cultures of stem cells and their
progenies has offered promising alternatives to recapitulate the in vivo
microenvironment, or stem cell niche, and has provided more specific cues for
proper stem cell differentiation, maintenance and culture. In particular, tissue
spheroids are cellular aggregates with defined cellular and extracellular
features and have provided optimal conditions for stem cell technology, both in
culture and for potential engraftment. Recent studies have focused on spheroid
formation and the developmental roles played by cellular and extracellular
signals necessary for cellular aggegation into spheroids. This review will
provide insights into the factors that regulate in vitro spheroid formation by
comparing them with their developmental counterparts in vivo. At the same time,
we will identify cellular and extracellular signals that could be used to
bioengineer spheroids with improved features according to their application.
Finally, this review will provide an overview of the applications to date of
spheroid cultures of stem cells and their progenies, providing insights for
future studies.
PMID- 26423299
TI - Nano-Engineered Environment for Nerve Regeneration: Scaffolds, Functional
Molecules and Stem Cells.
AB - One of the most complex systems in the human body is the nervous system, which is
divided into the central and peripheral nervous systems. The regeneration of the
CNS is a complex and challenging biological phenomenon hindered by the low
regenerative capacity of neurons and the prohibition factors in response to nerve
injuries. To date, no effective approach can achieve complete recovery and fully
restore the functions of the nervous system once it has been damaged.
Developments in neuroscience have identified properties of the local environment
with a critical role in nerve regeneration. Advances in biomaterials and
biomedical engineering have explored new approaches of constructing permissive
environments for nerve regeneration, thereby enabling optimism with regard to
nerve-injury treatment. This article reviews recent progress in nanoengineered
environments for aiding nerveinjury repair and regeneration, including
nanofibrous scaffolds, functional molecules, and stem cells.
PMID- 26423300
TI - The Influence of Diabetes Mellitus on Proliferation and Osteoblastic
Differentiation of MSCs.
AB - BACKGROUND: Diabetes mellitus (DM) is a widespread chronic metabolic disease
which has high mortality due to its complications. In addition to traditional
medication, stem cell transplantation therapeutics has become a brand-new and
prospective remedy for DM. With strong self-renewal and multi-potential ability,
mesenchymal stem cells (MSCs) are considered as ideal cell sources of cell
therapy for DM and many other diseases. However, not only do endogenous MSCs fail
to replace the impaired islet cells, but also transplanted MSCs fail to cure many
patients complicated with DM. Besides, quite a few DM patients suffer from high
risk of fracture and low efficiency of bone regeneration, which are often
associated with the osteoblastic differentiation of MSCs. Recently, a number of
researches have investigated that the changes in micro-environment by DM can
affect biological characteristics of MSCs through many factors. SUMMARY: In this
review, we summarize the developments in the influence of DM on proliferation and
osteoblastic differentiation of MSCs, and moreover, osteoporosis, obesity and
metabolism syndrome, as they are closely related to DM.
PMID- 26423301
TI - Induced pluripotent stem cell-derived mesenchymal stem cells: A leap toward
personalized therapies.
AB - Mesenchymal Stem/stromal cell (MSCs) transplantation procedures have been used
since the 1960's to treat leukemia and other diseases, but due to the risks
involved only patients with life threatening illnesses were typically subjected
to the transplantation procedure until the last decade. Recent advancements in
transplantation techniques have made it more feasible to use it for non-life
threatening diseases. However, the potential uses for stem cells are still
limited by their rarity, and, in the case of allogeneic transplants, graft-vs.
host complications. An evolving alternative to conventional stem cell therapies
is induced pluripotent stem-cell derived mesenchymal stem/stromal cells (iPSC-
MSCs), which have a multi-lineage potential comparable to conventionally acquired
MSCs with the added benefit of being less immunoreactive. However there are still
many hurdles left to be overcome before they can be used regularly for
personalized therapies. This review will focus on recent advancements that have
been made regarding the role MSCs play in tumor development and the potential
uses iPSC-MSCs may have in future cancer treatment.
PMID- 26423302
TI - Nonparametric inference for the joint distribution of recurrent marked variables
and recurrent survival time.
AB - Time between recurrent medical events may be correlated with the cost incurred at
each event. As a result, it may be of interest to describe the relationship
between recurrent events and recurrent medical costs by estimating a joint
distribution. In this paper, we propose a nonparametric estimator for the joint
distribution of recurrent events and recurrent medical costs in right-censored
data. We also derive the asymptotic variance of our estimator, a test for
equality of recurrent marker distributions, and present simulation studies to
demonstrate the performance of our point and variance estimators. Our estimator
is shown to perform well for a wide range of levels of correlation, demonstrating
that our estimators can be employed in a variety of situations when the
correlation structure may be unknown in advance. We apply our methods to
hospitalization events and their corresponding costs in the second Multicenter
Automatic Defibrillator Implantation Trial (MADIT-II), which was a randomized
clinical trial studying the effect of implantable cardioverter-defibrillators in
preventing ventricular arrhythmia.
PMID- 26423296
TI - Stem Cells in Skeletal Tissue Engineering: Technologies and Models.
AB - This review surveys the use of pluripotent and multipotent stem cells in skeletal
tissue engineering. Specific emphasis is focused on evaluating the function and
activities of these cells in the context of development in vivo, and how
technologies and methods of stem cell-based tissue engineering for stem cells
must draw inspiration from developmental biology. Information on the embryonic
origin and in vivo differentiation of skeletal tissues is first reviewed, to shed
light on the persistence and activities of adult stem cells that remain in
skeletal tissues after embryogenesis. Next, the development and differentiation
of pluripotent stem cells is discussed, and some of their advantages and
disadvantages in the context of tissue engineering are presented. The final
section highlights current use of multipotent adult mesenchymal stem cells,
reviewing their origin, differentiation capacity, and potential applications to
tissue engineering.
PMID- 26423303
TI - Beneficial effect of zinc chloride and zinc ionophore pyrithione on attenuated
cardioprotective potential of preconditioning phenomenon in STZ-induced diabetic
rat heart.
AB - Ischemic preconditioning (IPC) is well demonstrated to produce cardioprotection
by phosphorylation and subsequent inactivation of glycogen synthase kinase-3beta
(GSk-3beta) in the normal rat heart, but its effect is attenuated in the diabetic
rat heart. This study was designed to investigate the effect of zinc chloride and
zinc ionophore pyrithione (ZIP) on the attenuated cardioprotective potential of
IPC in the diabetic rat heart. Diabetes mellitus (DM) was induced by a single
intraperitoneal administration of streptozotocin (STZ) (50 mg/kg; i.p). The
isolated perfused rat heart was subjected to 30 minutes of ischemia followed by
120 minutes of reperfusion. Myocardial infarct size was estimated by
triphenyltetrazolium chloride (TTC) staining and cardiac injury was measured by
estimating lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the
coronary effluent. Also, GSK-3beta was measured and neutrophil accumulation was
measured by estimating myeloperoxidase (MPO) levels. IPC significantly decreased
the myocardial infarct size, the release of LDH and CK-MB, the GSK-3beta levels
and the MPO levels in the normal rat heart. Pre- and post-ischemic treatment with
zinc chloride and zinc ionophore pyrithione (ZIP) in the normal and diabetic rat
hearts significantly decreased the myocardial infarct size, the level of CK-MB
and LDH in the coronary effluent and GSK-3beta and MPO levels. Our results
suggest that pharmacological preconditioning with zinc chloride and ZIP
significantly restored the attenuated cardioprotective potential of IPC in the
diabetic rat heart.
PMID- 26423304
TI - [Hospital safety in paediatrics].
PMID- 26423305
TI - Benefit-harm analysis and charts for individualized and preference-sensitive
prevention: example of low dose aspirin for primary prevention of cardiovascular
disease and cancer.
AB - BACKGROUND: Clinical practice guidelines provide separate recommendations for
different diseases that may be prevented or treated by the same intervention.
Also, they commonly provide recommendations for entire populations but not for
individuals. To address these two limitations, our aim was to conduct benefit
harm analyses for a wide range of individuals using the example of low dose
aspirin for primary prevention of cardiovascular disease and cancer and to
develop Benefit-Harm Charts that show the overall benefit-harm balance for
individuals. METHODS: We used quantitative benefit-harm modeling that included 16
outcomes to estimate the probability that low dose aspirin provides more benefits
than harms for a wide range of men and women between 45 and 84 years of age and
without a previous myocardial infarction, severe ischemic stroke, or cancer. We
repeated the quantitative benefit-harm modeling for different combinations of
age, sex, and outcome risks for severe ischemic and hemorrhagic stroke,
myocardial infarction, cancers, and severe gastrointestinal bleeds. The analyses
considered weights for the outcomes, statistical uncertainty of the effects of
aspirin, and death as a competing risk. We constructed Benefit-Harm Charts that
show the benefit-harm balance for different combinations of outcome risks.
RESULTS: The Benefit-Harm Charts ( http://www.benefit-harm-balance.com ) we have
created show that the benefit-harm balance differs largely across a primary
prevention population. Low dose aspirin is likely to provide more benefits than
harms in men, elderly people, and in those at low risk for severe
gastrointestinal bleeds. Individual preferences have a major impact on the
benefit-harm balance. If, for example, it is a high priority for individuals to
prevent stroke and severe cancers while severe gastrointestinal bleeds are deemed
to be of little importance, the benefit-harm balance is likely to favor low dose
aspirin for most individuals. Instead, if severe gastrointestinal bleeds are
judged to be similarly important compared to the benefit outcomes, low dose
aspirin is unlikely to provide more benefits than harms. CONCLUSIONS: Benefit
Harm Charts support individualized benefit-harm assessments and decision making.
Similarly, individualized benefit-harm assessments may allow guideline developers
to issue more finely granulated recommendations that reduce the risk of over- and
underuse of interventions. The example of low dose aspirin for primary prevention
of cardiovascular disease and cancer shows that it may be time for guideline
developers to provide combined recommendations for different diseases that may be
prevented or treated by the same intervention.
PMID- 26423307
TI - Cor Triatriatum Sinister - Source of Unusual Thrombogenesis in Mitral Stenosis.
PMID- 26423306
TI - Serum Phenylalanine, Tyrosine, and their Ratio in Acute Ischemic Stroke: on the
Trail of a Biomarker?
AB - Fast diagnosis and appropriate treatment are of utmost importance to improving
the outcome in patients with acute ischemic stroke (AIS). A rapid and sensitive
blood test for ischemic stroke is required. The aim of this study was to examine
the usefulness of phenylalanine (PHE) and tyrosine (TYR) as diagnostic biomarkers
in AIS. Serum levels of PHE and TYR, measured using HPLC, and their ratio
(PHE/TYR) were compared between 45 patients with AIS and 40 healthy control
subjects. The relationship between PHE/TYR and the serum levels of several
cytokines were also examined. PHE/TYR was significantly higher in AIS patients
than in healthy controls (1.75 vs 1.24, p < 0.001). A receiver operating
characteristic (ROC) curve analysis of PHE/TYR in AIS patients relative to
healthy controls revealed promising sensitivity and specificity, which at an
optimal cutoff of 1.45 were 76 and 85 %, respectively. PHE/TYR was positively
correlated with interleukin (IL)-1beta (r = 0.37, p = 0.011) and IL-6 (r = 0.33,
p = 0.025). This study shows that PHE/TYR is highly elevated in the acute phase
of AIS, and that this elevation is coupled to the inflammatory response. The ROC
analysis documents the possible value of PHE/TYR as a biomarker for AIS and
demonstrates its clinical potential as a blood-based test for AIS.
PMID- 26423308
TI - Low-dose warfarin with prothrombin time-international normalized ratio between
1.6 and 2.6 for very old Japanese patients.
PMID- 26423310
TI - Hospitals are wrong to ban e-cigarette use.
PMID- 26423309
TI - IL-17-producing gammadeltaT cells are regulated by estrogen during development of
experimental arthritis.
AB - Interleukin-17 (IL-17) drives inflammation and destruction of joints in
rheumatoid arthritis (RA). The female sex hormone 17beta-estradiol (E2) inhibits
experimental arthritis. gammadeltaT cells are significant producers of IL-17,
thus the aim of this study was to investigate if E2 influenced IL-17(+)
gammadeltaT cells during arthritis development using a variety of experimental RA
models: collagen-induced arthritis (CIA); antigen-induced arthritis (AIA); and
collagen antibody-induced arthritis (CAIA). We demonstrate that E2 treatment
decreases IL-17(+) gammadeltaT cell number in joints, but increases IL-17(+)
gammadeltaT cells in draining lymph nodes, suggesting an E2-mediated prevention
of IL-17(+) gammadeltaT cell migration from lymph nodes to joints, in concert
with our recently reported effects of E2 on Th17 cells (Andersson et al., 2015).
E2 did neither influence the general gammadeltaT cell population nor IFNgamma(+)
gammadeltaT cells, implying a selective regulation of IL-17-producing cells. In
conclusion, this study contributes to the understanding of estrogen's role in
autoimmune disease.
PMID- 26423311
TI - Minimum unit pricing: better late than never.
PMID- 26423312
TI - Mesoporous Fluorinated Metal-Organic Frameworks with Exceptional Adsorption of
Fluorocarbons and CFCs.
AB - Two mesoporous fluorinated metal-organic frameworks (MOFs) were synthesized from
extensively fluorinated tritopic carboxylate- and tetrazolate-based ligands. The
tetrazolate-based framework MOFF-5 has an accessible surface area of 2445 m(2) g(
1), the highest among fluorinated MOFs. Crystals of MOFF-5 adsorb hydrocarbons,
fluorocarbons, and chlorofluorocarbons (CFCs)-the latter two being ozone
depleting substances and potent greenhouse species-with weight capacities of up
to 225%. The material exhibits an apparent preference for the adsorption of non
spherical molecules, binding unusually low amounts of both tetrafluoromethane and
sulfur hexafluoride.
PMID- 26423313
TI - Immunopathogenesis of olmesartan-associated enteropathy.
AB - BACKGROUND: Olmesartan-associated enteropathy (OAE) is characterised by
diarrhoea, nausea, vomiting, abdominal pain, weight loss and severe sprue-like
enteropathy, all of which are resolved after discontinuation of olmesartan
medoximil. AIM: To determine the mechanistic similarities of OAE with coeliac
sprue. METHODS: Duodenal biopsies were extracted from OAE patients before (n =
11) or after (n = 17) discontinuation of olmesartan medoxomil (on or off
olmesartan medoxomil). There were seven 'on/off' paired samples. Formalin-fixed
biopsies were stained for CD8, CD4, FoxP3, IL-15R and psmad 2/3. Caco2 cells
(human colonic epithelial line) were treated with olmesartan medoxomil and
stained for IL-15, IL-15R and ZO-1. RESULTS: In the 'on olmesartan medoxomil'
duodenal biopsies, a significant increase in the numbers of CD8+ cells and the
number of cells that are FoxP3+ (a regulatory T-cell marker) are present in the
duodenum as compared to the duodenal biopsies from patients who discontinued
olmesartan medoxomil. IL15R expression is also increased with olmesartan
medoxomil use. Evaluation of the effect of olmesartan medoxomil upon Caco-2 cells
demonstrated that IL15 expression is increased in response to olmesartan
medoxomil treatment. Further, ZO-1, a tight junction protein, is disrupted in
olmesartan medoxomil-treated Caco-2 cells. CONCLUSIONS: Olmesartan-associated
enteropathy shares many features with coeliac disease, including symptoms and
immunopathogenic pathways, such as increased numbers of CD8+ cells and
corresponding overexpression of IL15 by epithelial cells. Taken together, the
treatment of epithelial cells with olmesartan medoxomil induces a response by
intestinal epithelial cells that is similar to the innate effects of gluten upon
the epithelium of coeliac patients.
PMID- 26423314
TI - Evaluation of an automated fetal myocardial performance index.
AB - OBJECTIVE: To compare automated measurements of the fetal left myocardial
performance index (MPI) with manual measurements for absolute value,
repeatability and waveform acceptability. METHODS: This was a multicenter
international online study using images from uncomplicated, morphologically
normal singleton pregnancies (16-38 weeks' gestation). Single Doppler ultrasound
cardiac cycle images of 25 cases were selected, triplicated and randomized (n =
75). Six senior observers, unaware of the repetition of images, manually
calculated MPI for each waveform and the results were compared with automation.
Intraobserver repeatability and interobserver reproducibility were assessed using
intraclass correlation coefficients (ICCs) and 95% CI. The agreement between each
observer's manual MPI measurements and corresponding automated measurements was
evaluated using Bland-Altman plots and ICCs with 95% CI. The degree of variation
between experts in the classification of fetal MPI waveform quality was assessed
using individual cardiac cycle left MPI images previously classified by two
authors as 'optimal', 'suboptimal' or 'unacceptable', with 30 images selected for
each quality group. Ten images in each category were duplicated and the resulting
120 images were randomized and then classified online by five observers. The
kappa statistic (kappa) was used to demonstrate interobserver and intraobserver
agreement and agreement of classifications by the five observers. RESULTS: The
automated measurement software returned the same value for any given image,
resulting in an ICC of 1.00. Manual measurements had intraobserver repeatability
ICC values ranging from 0.69 to 0.97, and the interobserver reproducibility ICC
was 0.78. Comparison of automated vs manual MPI absolute measurements for each
observer gave ICCs ranging from 0.77 to 0.96. Interobserver image quality
classification agreement gave k = 0.69 (P < 0.001), and the intraobserver
agreement was variable (kappa ranging from 0.40 to 0.81). CONCLUSIONS: Automated
fetal MPI provides superior repeatability and reproducibility to manual
methodology. Additionally, experts vary significantly when classifying
suitability of fetal MPI waveforms. Automated MPI may facilitate clinical
translation by removing human subjectivity. Copyright (c) 2015 ISUOG. Published
by John Wiley & Sons Ltd.
PMID- 26423315
TI - Long-term Symptomatic Endoleak type 1a as a Result of Aortic Endograft Material
Fatigue.
PMID- 26423316
TI - Peritumoral tissue compression is predictive of exudate flux in a rat model of
cerebral tumor: an MRI study in an embedded tumor.
AB - MRI estimates of extracellular volume and tumor exudate flux in peritumoral
tissue are demonstrated in an experimental model of cerebral tumor. Peritumoral
extracellular volume predicted the tumor exudate flux. Eighteen RNU athymic rats
were inoculated intracerebrally with U251MG tumor cells and studied with dynamic
contrast enhanced MRI (DCE-MRI) approximately 18 days post implantation. Using a
model selection paradigm and a novel application of Patlak and Logan plots to DCE
MRI data, the distribution volume (i.e. tissue porosity) in the leaky rim of the
tumor and that in the tissue external to the rim (the outer rim) were estimated,
as was the tumor exudate flow from the inner rim of the tumor through the outer
rim. Distribution volume in the outer rim was approximately half that of the
inner adjacent region (p < 1 * 10(-4)). The distribution volume of the outer ring
was significantly correlated (R(2) = 0.9) with tumor exudate flow from the inner
rim. Thus, peritumoral extracellular volume predicted the rate of tumor exudate
flux. One explanation for these data is that perfusion, i.e. the delivery of
blood to the tumor, was regulated by the compression of the mostly normal tissue
of the tumor rim, and that the tumor exudate flow was limited by tumor perfusion.
PMID- 26423317
TI - Simethicone adjunct to polyethylene glycol improves small bowel capsule endoscopy
imaging in non-Crohn's disease patients.
AB - BACKGROUND: Currently, there is no standardized protocol for bowel preparation
before small bowel capsule endoscopy (SBCE). This study aimed to investigate the
effect of simethicone combined with polyethylene glycol (PEG) on the
visualization quality (VQ) of the SBCE in patients with or without known or
suspected Crohn's disease (CD). METHODS: This observational, prospective, single
center study included consecutive patients undergoing a SBCE between 2007 and
2008. Patients received either a standard bowel cleansing preparation of 2 L PEG
and 80 mg simethicone orally 12 and 1 h before SBCE respectively (Group A) or
only PEG (Group B). VQ, based on scores for luminal bubbles in frames taken from
the small intestine, examination completeness, SBCE diagnostic yield, gastric and
small bowel transit times were recorded. RESULTS: Of the 115 patients finally
included (Group A, n=56 and Group B, n=59) the cecum was visualized in 103
(89.6%). Simethicone overall improved the VQ in the proximal [OR: 2.43 (95%CI:
1.08-5.45), P=0.032] but not in the distal bowel segment (P=0.064). Nevertheless,
this effect was not observed in patients undergoing SBCE for either known or
suspected CD. CONCLUSION: Simethicone as an adjunct to PEG for bowel preparation
in patients undergoing SBCE significantly improved the VQ in non-CD patients.
PMID- 26423318
TI - Surgery for scoliosis in Duchenne muscular dystrophy.
AB - BACKGROUND: Scoliosis in patients with Duchenne muscular dystrophy (DMD) is
usually progressive and is treated with surgery. However, it is unclear whether
the existing evidence is sufficiently scientifically rigorous to support a
recommendation for spinal surgery for most patients with DMD and scoliosis. This
is an updated review, and an updated search was undertaken in which no new
studies were found for inclusion. OBJECTIVES: To determine the effectiveness and
safety of spinal surgery in patients with DMD with scoliosis. We intended to test
whether spinal surgery is effective in increasing survival and improving
respiratory function, quality of life, and overall functioning, and whether
spinal surgery is associated with severe adverse effects. SEARCH METHODS: On 16
June 2015 we searched the Cochrane Neuromuscular Disease Group Specialized
Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
EMBASE, and CINAHL Plus. We also searched ProQuest Dissertation and Thesis
database (January 1980 to June 2015), the National Institutes of Health Clinical
Trials Database (6 January 2015), and the WHO International Clinical Trials
Registry Platform (17 June 2015), and checked references. We imposed no language
restrictions. SELECTION CRITERIA: We planned to include controlled clinical
trials using random or quasi-random allocation of treatment evaluating all forms
of spinal surgery for scoliosis in patients with DMD in the review. The control
interventions would have been no treatment, non-operative treatment, or a
different form of spinal surgery. DATA COLLECTION AND ANALYSIS: We used standard
methodological procedures expected by The Cochrane Collaboration. Two review
authors independently examined the search results and evaluated the study
characteristics against inclusion criteria in order to decide which studies to
include in the review. MAIN RESULTS: Of the 49 relevant studies we found, none
met the inclusion criteria for the review because they were not clinical trials,
but prospective or retrospective reviews of case series. AUTHORS' CONCLUSIONS:
Since no randomized controlled clinical trials were available to evaluate the
effectiveness of scoliosis surgery in patients with DMD, we can make no good
evidence-based conclusion to guide clinical practice. Patients with scoliosis
should be informed as to the uncertainty of benefits and potential risks of
surgery for scoliosis. Randomized controlled trials are needed to investigate the
effectiveness of scoliosis surgery, in terms of quality of life, functional
status, respiratory function, and life expectancy.
PMID- 26423319
TI - Misspecified poisson regression models for large-scale registry data: inference
for 'large n and small p'.
AB - Poisson regression is an important tool in register-based epidemiology where it
is used to study the association between exposure variables and event rates. In
this paper, we will discuss the situation with 'large n and small p', where n is
the sample size and p is the number of available covariates. Specifically, we are
concerned with modeling options when there are time-varying covariates that can
have time-varying effects. One problem is that tests of the proportional hazards
assumption, of no interactions between exposure and other observed variables, or
of other modeling assumptions have large power due to the large sample size and
will often indicate statistical significance even for numerically small
deviations that are unimportant for the subject matter. Another problem is that
information on important confounders may be unavailable. In practice, this
situation may lead to simple working models that are then likely misspecified. To
support and improve conclusions drawn from such models, we discuss methods for
sensitivity analysis, for estimation of average exposure effects using aggregated
data, and a semi-parametric bootstrap method to obtain robust standard errors.
The methods are illustrated using data from the Danish national registries
investigating the diabetes incidence for individuals treated with antipsychotics
compared with the general unexposed population.
PMID- 26423320
TI - Effects of alternating hands during in-hospital one-handed chest compression: A
randomised cross-over manikin trial.
AB - OBJECTIVE: We evaluated the decrease in chest compression depth during continuous
one-handed chest compression (OHCC) in an in-hospital paediatric arrest setting,
and whether switching hands could delay the decrease in chest compression depth.
METHODS: In total, 30 healthcare providers were randomised into groups A and B.
Group A performed test 1 (chest compressors alternated hands every 30 s in 2 min
of OHCC), followed by test 2 (chest compressors used one hand for 2 min without
switching to the other hand) and group B, vice versa. Participants performed 2
min continuous OHCC on a paediatric manikin on a bed. Mean compression depth
(MCD) and mean compression rate (MCR) were analysed at 30 s intervals. RESULTS:
The MCDs in 30 s intervals changed significantly with time passed in tests 1 and
2 (0-30 s: 43.4 +/- 7.4 vs 42.8 +/- 7.6 mm, 30-60 s: 42.8 +/- 8.7 vs 40.3 +/- 8.8
mm, 60-90 s: 40.5 +/- 8.9 vs 38.2 +/- 9.6 mm, 90-120 s: 40.2 +/- 10.2 vs 36.9 +/-
9.7 mm; P < 0.01). However, with the exception of the first 30 s interval, MCD in
test 1 showed significantly higher values than in test 2 (P < 0.05). The MCRs in
30 s intervals did not change significantly with time passed in all tests and
were not different between the two tests. All hand-off times measured during
switching hands in test 1 were less than 1 s. CONCLUSIONS: Chest compression
depth decreased significantly when continuous OHCC was performed without
switching hands. Alternating hands every 30 s can delay the decrease in MCD and
maintain deeper MCD for longer.
PMID- 26423321
TI - Profiles of Resilience and Growth in Youth With Cancer and Healthy Comparisons.
AB - OBJECTIVE: Inconsistent links between posttraumatic stress symptoms (PTS) and
posttraumatic growth (PTG) in youth following a stressful life event have been
observed in previous literature. Latent profile analysis (LPA) provides a novel
approach to examine the heterogeneity of relations between these constructs.
METHOD: Participants were 435 youth (cancer group=253; healthy comparisons = 182)
and one parent. Children completed measures of PTS, PTG, and a life-events
checklist. Parents reported on their own PTS and PTG. LPA was conducted to
identify distinct adjustment classes. RESULTS: LPA revealed three profiles. The
majority of youth (83%) fell into two resilient groups differing by levels of
PTG. Several factors predicted youth's profile membership. CONCLUSIONS: PTS and
PTG appear to be relatively independent constructs, and their relation is
dependent on contextual factors. The majority of youth appear to be resilient,
and even those who experience significant distress were able to find benefit.
PMID- 26423322
TI - Illness Uncertainty, Global Psychological Distress, and Posttraumatic Stress in
Pediatric Cancer: A Preliminary Examination Using a Path Analysis Approach.
AB - OBJECTIVE: To investigate the relationship of illness uncertainty (IU) to global
psychological distress (GPD) and posttraumatic stress symptomatology (PTSS) using
a path analysis approach. METHODS: Participants were 105 caregivers (MAge = 36.9
years, standard deviation [SD] = 8.7) of children (MAge = 8.6 years, SD = 5.0)
with newly diagnosed cancer. A path analysis model examined the indirect and
direct effects of each IU subscale on PTSS through GPD. RESULTS: The final
model accounted for 47.30% of the variance in PTSS, and the ambiguity facet of IU
had a significant indirect effect on PTSS through GPD. Lack of clarity and
unpredictability were not significant predictors. CONCLUSIONS: Ambiguity
experienced by parents may be salient in the development of PTSS. Future research
should examine these relationships longitudinally in larger samples to better
understand adjustment in parents of children with cancer.
PMID- 26423323
TI - Epidemiological Profile of Wild Rabies in Brazil (2002-2012).
AB - Rabies is one of the most important zoonosis in the world with high impact on
public health. Studies report the presence of Lyssavirus in reservoirs of the
wild cycle, highlighting the role of wild canines, marmosets, and vampire and non
vampire bats as potential vectors of the disease to domestic animals and human
beings. Therefore, the reintroduction of rabies in urban environments from
reservoirs of the wild cycle is a matter of concern. This study describes the
profile of rabies cases documented in Brazil from 2002 to 2012, with emphasis on
the wild transmission cycle of the disease. We carried out a descriptive study
using records with information on the time of infection, persons with infection
and location of confirmed cases of rabies in humans and animals, as well as data
on anti-rabies treatments obtained from the Information System of Notifiable
Diseases (Sinan) database. Within the study period, 82 cases of rabies
transmitted by wild animals to humans were reported, predominantly in rural areas
of the northern and north-eastern regions. Of the cases in humans, 72% did not
receive post-exposure prophylaxis. Among wild mammals, vampire bats were the most
frequent vectors of the disease. In the north-east region, 460 terrestrial wild
mammals were reported with confirmed rabies. Over the study period, 1703 bats
were reported to carry the rabies virus. In the south-east region, the most
frequently reported carriers of the virus were non-vampire bats. The midwest and
northern regions presented a lower number of records of rabies cases among
terrestrial wild mammals. However, the high number of rabies cases among bovines
reflects the role of the vampire bat as a maintainer of the rabies virus in the
rural cycle. The present results are key to adjust the planning of rabies control
in Brazil to the current epidemiological trends.
PMID- 26423324
TI - Putting Everything in Context.
AB - In response to Casasanto, Brookshire, and Ivry (2015), we address four points:
First, we engaged in conceptual replications of Brookshire, Casasanto, and Ivry
(2010), not direct replications. Second, we did not question the validity of
Brookshire et al.'s (2010) results, nor the similar findings of other
researchers, but instead explained divergent findings within an integrated
theoretical framework. Third, challenges to the construct of automaticity,
including ours, were widespread, long before Brookshire et al.'s (2010) article.
Fourth, the planned comparisons that we reported tested our theoretical claims
and offered strong evidence for them.
PMID- 26423325
TI - F11 is associated with recurrent VTE in women. A prospective cohort study.
AB - Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not
well described. Our aim was to investigate if common genetic variants, previously
found to contribute to the prediction of first time thrombosis in women, were
associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a
Swedish nationwide case-control study (2002-2009). A cohort of 1,010 women with
first time VTE was followed up until a recurrent event, death or November 2011.
The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11
rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical
variables. Recurrence rate was calculated as the number of events over the
accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier
curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and
95% confidence intervals (95% CI) between groups. A total of 101 recurrent events
occurred during a mean follow-up time of five years. The overall recurrence rate
was 20 per 1,000 person-years (95% CI; 16-24). The recurrence rate was highest in
women with unprovoked first event and obesity. Carriers of the risk alleles of F5
rs6025 (HR=1.7 (95% CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95% CI; 1.1-3.0))
had significantly higher rates of recurrence compared to non-carriers. The
cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11
rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025
and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is
of potential clinical relevance for risk prediction.
PMID- 26423326
TI - Marine reserves can enhance ecological resilience.
AB - The goals of ecosystem-based management (EBM) include protecting ecological
resilience, the magnitude of a perturbation that a community can withstand and
remain in a given state. As a tool to achieve this goal, no-take marine reserves
may enhance resilience by protecting source populations or reduce it by
concentrating fishing in harvested areas. Here, we test whether spatial
management with marine reserves can increase ecological resilience compared to
non-spatial (conventional) management using a dynamic model of a simplified fish
community with structured predation and competition that causes alternative
stable states. Relative to non-spatial management, reserves increase the
resilience of the desired (predator-dominated) equilibrium state in both
stochastic and deterministic environments, especially under intensive fishing. As
a result, spatial management also increases the feasibility of restoring degraded
(competitor-dominated) systems, particularly if combined with culling of
competitors or stock enhancement of adult predators.
PMID- 26423327
TI - A pilot study examining if satisfaction of basic needs can ameliorate negative
effects of shift work.
AB - The objective of the present study was to investigate if satisfaction of the
basic needs of autonomy, competence, and relatedness is related to shift work
tolerance, specifically physical and mental fatigue, insomnia, and digestive
troubles in a sample of shift workers. This is a cross-sectional pilot
questionnaire study, including 252 shift workers employed in a municipality in
Norway. Autonomy was negatively related to physical fatigue and digestive
troubles, while competence was negatively related to mental fatigue. Relatedness
showed significant correlations with insomnia and mental fatigue, but did not
reach significance in the regression model controlling for the two other basic
needs as well as work scheduling, night work exposure, and sleep medication.
Sleep medication was significant in the final regression model for insomnia, but
unrelated to fatigue and digestive troubles. The demographic variables, work
hours per week, work schedule, and night work exposure were unrelated to all four
measures of shift work tolerance. Autonomy and competence may be more important
for fatigue and digestive troubles among shift workers than work arrangement
variables, night work exposure, and sleep medication use.
PMID- 26423328
TI - Effects of mop handle height on shoulder muscle activity and perceived exertion
during floor mopping using a figure eight method.
AB - The aim of this study was to investigate effects of mop handle height on
electromyographic (EMG) activities of the shoulder muscles and perceived exertion
for the shoulder area during floor mopping using a figure eight method. An
experimental study with 13 cleaners was conducted using surface EMG and category
ratio (CR-10) scale. EMG activity was recorded unilaterally from the upper
trapezius, infraspinatus, anterior and middle deltoid muscles. Each subject
performed four trials of mopping and each trial consisted of using a different
mop handle height (mop adjustment at the level of shoulder, chin, nose and eye)
in randomized order. EMG data were normalized to a percentage of maximal
voluntary contraction (%MVC). The muscle activities were assessed by estimating
the 10th, 50th and 90th percentiles of the amplitude probability distribution
function (APDF) of the EMG signals and analysed by linear mixed model analysis.
Results showed that shoulder muscle activity was significantly lower when the mop
handle height was adjusted to shoulder level or chin level as compared to eye
level. These findings were supported by subjective ratings of exertion. It seems
that mop handle height adjustment between shoulder and chin level may be
recommended as a basis for figure eight mopping.
PMID- 26423329
TI - Silicosis and renal disease: insights from a case of IgA nephropathy.
AB - A 68-yr-old male, smoker, is admitted for proteinuria (2,800 mg/24 h) and reduced
renal function (serum creatinine 2 mg/dl, GFR 35 ml/min). Renter, he started
working 20-yr-old as a sandstone cave miner. Despite the high levels of silica
dusts, he reported no mandatory use of airways protection devices during the
first 25 yr of activity. No clinical or radiological signs of silicosis or
pneumoconiosis where reported until the year of retirement (1997). Erythrocyte
sedimentation rate (91 mm/h) and C reactive protein (35 mg/l) suggested a pro
inflammatory status. High serum IgA was found (465 mg/dl). A renal biopsy
identified glomerular sclerosis with IgA deposition, signs of diffuse vasculitis
and tubular atrophia suggesting a diagnosis of IgA nephropathy. Chest X-Rays
showed emphysema and diffuse nodularity suggesting diagnosis of silicosis. Chest
tomography was also positive for mild signs of silicosis with silicotic nodules
and without honeycombing. IgA nephropathy is the most common type of
glomerulonephritis worldwide. Several clues suggest a genetic or acquired
abnormality of immune system as a trigger of the increased production of IgA. In
our case report, simultaneous kidney and pulmonary disease could suggest same
triggers (e.g. exposure to virus, bacteria or environmental agents) inducing IgA
synthesis and pulmonary immune system activation.
PMID- 26423330
TI - Relations of biomarkers of manganese exposure and neuropsychological effects
among welders and ferroalloy smelters.
AB - The objective of present study was to assess relationship between biomarkers of
Manganese (Mn) and neuropsychological effects. The study was carried out on 27
welders and 31 ferroalloy smelters as Mn-exposed groups and 30 office workers as
unexposed controls. Air Mn concentrations were determined according to NIOSH
method 7300. The biological samples were prepared using microwave assisted acid
digestion and all samples were analyzed by graphite furnace- atomic absorption
spectroscopy (GF-AAS) in order to determine manganese. Questionnaire 16 (Q16) and
Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to
evaluate the neuropsychological effects. The mean concentrations of air Mn for
the welder and ferroalloy smelter groups were 0.023 +/- 0.012 mg/m(3) and 0.008
+/- 0.005 mg/m(3), respectively. Manganese concentrations in blood, urine, and
toenail samples of exposed workers ranged between 1.80-32.60 (ug/l), 1.00-42.50
(ug/l), and 0.10-6.08 (ug/g), respectively. Mean Mn concentrations in all
biological samples of cases were significantly higher than unexposed controls
(p<0.05). A moderate relationship was observed between biomarkers of Mn exposure,
air Mn, Q16 as well as some neurocognitive outcome measures. The present study
shows that blood Mn, urine Mn and toenail Mn could be used to distinguish Mn
exposed workers from unexposed population at the group level.
PMID- 26423331
TI - Evaluation of ergonomic physical risk factors in a truck manufacturing plant:
case study in SCANIA Production Angers.
AB - The aims of this study were 1) to assess the ergonomic physical risk factors from
practitioner's viewpoint in a truck assembly plant with an in-house observational
method and the NIOSH lifting equation, and 2) to compare the results of both
methods and their differences. The in-house ergonomic observational method for
truck assembly i.e. the SCANIA Ergonomics Standard (SES) and the NIOSH lifting
equation were applied to evaluate physical risk factors and lifting of loads by
operators. Both risk assessment approaches revealed various levels of risk,
ranging from low to high. Two workstations were identified by the SES method as
high risk. The NIOSH lifting index (LI) was greater than two for four lifting
tasks. The results of the SES method disagreed with the NIOSH lifting equation
for lifting tasks. Moreover, meaningful variations in ergonomic risk patterns
were found for various truck models at each workstation. These results provide a
better understanding of the physical ergonomic exposure from practitioner's point
of view in the automotive assembly plant.
PMID- 26423332
TI - Work-family conflict and sleep disturbance: the Malaysian working women study.
AB - This study aimed at assessing effect of the four dimensions of work-family
conflicts (strain and time-based work interference into family and family
interference into work) on sleep disturbance in Malaysian working women. This
cross-sectional study was conducted among 325 Malaysian married working women.
Multiple-stage simple random sampling method was used to recruit women from
public service departments of Malaysia. Self-administrated questionnaires were
used to measure the study variables and data were analyzed using SPSS version 21.
We found that high level of the four dimensions of work-family conflicts
significantly increase sleep disturbance. Our analyses also revealed an age
dependent effect of the work-family conflict on sleep disturbance. Women in their
20 to 30 yr old suffer from sleep disturbance due to high level of time-based and
strain-based work-interference into family. However, the quality of sleep among
women aged 30-39 were affected by strain-based family-interference into work.
Finally, women older than 40 yr had significantly disturbed sleep due to strain
based work-interference into family as well as time-based family interference
into work. Our findings showed that sleep quality of working women might be
disturbed by experiencing high level of work-family conflict. However, the
effects of inter-role conflicts on sleep varied among different age groups.
PMID- 26423333
TI - HIV testing and attitudes among the working-age population of Japan: annual
health checkups may offer an effective way forwards.
AB - In Japan, Voluntary Counselling and Testing (VCT) for HIV has been recommended
for people concerned about their infection risk, especially those in high-risk
groups. Although HIV awareness has declined in this country somewhat during
recent years, the number of newly-infected cases has been increasing. The purpose
of the current study therefore, was to determine the prevalence of HIV testing,
individuals' reasons for being tested, and the overall acceptance of HIV testing
among working-age Japanese. We utilized an anonymous, nationwide survey which was
administered to a total of 3,055 participants aged 20-69 yr. The lifetime
prevalence of HIV testing was 14% (2% within the past year). A gap was observed
between a prior history of HIV testing and willingness to be tested in future
(32%) or willingness to be tested during health checkups in the workplace (41%).
HIV testing appears to have only been conducted among a limited number of working
age Japanese adults, even though some reported a willingness to be tested.
Opportunities for VCT during workplace health checkups might offer an immediate
and positive way forwards in the fight against HIV; however, privacy protection
for test results and the acceptance of HIV-positive employees should be carefully
considered in the workplace.
PMID- 26423334
TI - Dynamics of leaf gas exchange, chlorophyll fluorescence and stem diameter changes
during freezing and thawing of Scots pine seedlings.
AB - Boreal trees experience repeated freeze-thaw cycles annually. While freezing has
been extensively studied in trees, the dynamic responses occurring during the
freezing and thawing remain poorly understood. At freezing and thawing, rapid
changes take place in the water relations of living cells in needles and in stem.
While freezing is mostly limited to extracellular spaces, living cells dehydrate,
shrink and their osmotic concentration increases. We studied how the freezing
thawing dynamics reflected on leaf gas exchange, chlorophyll fluorescence and
xylem and living bark diameter changes of Scots pine (Pinus sylvestris L.)
saplings in controlled experiments. Photosynthetic rate quickly declined
following ice nucleation and extracellular freezing in xylem and needles, almost
parallel to a rapid shrinking of xylem diameter, while that of living bark
followed with a slightly longer delay. While xylem and living bark diameters
responded well to decreasing temperature and water potential of ice, the
relationship was less consistent in the case of increasing temperature. Xylem
showed strong temporal swelling at thawing suggesting water movement from bark.
After thawing xylem diameter recovered to a pre-freezing level but living bark
remained shrunk. We found that freezing affected photosynthesis at multiple
levels. The distinct dynamics of photosynthetic rate and stomatal conductance
reveals that the decreased photosynthetic rate reflects impaired dark reactions
rather than stomatal closure. Freezing also inhibited the capacity of the light
reactions to dissipate excess energy as heat, via non-photochemical quenching,
whereas photochemical quenching of excitation energy decreased gradually with
temperature in agreement with the gas exchange data.
PMID- 26423335
TI - In situ 13CO2 pulse labelling of field-grown eucalypt trees revealed the effects
of potassium nutrition and throughfall exclusion on phloem transport of
photosynthetic carbon.
AB - Potassium (K) is an important limiting factor of tree growth, but little is known
of the effects of K supply on the long-distance transport of photosynthetic
carbon (C) in the phloem and of the interaction between K fertilization and
drought. We pulse-labelled 2-year-old Eucalyptus grandis L. trees grown in a
field trial combining K fertilization (+K and -K) and throughfall exclusion (+W
and -W), and we estimated the velocity of C transfer by comparing time lags
between the uptake of (13)CO2 and its recovery in trunk CO2 efflux recorded at
different heights. We also analysed the dynamics of the labelled photosynthates
recovered in the foliage and in the phloem sap (inner bark extract). The mean
residence time of labelled C in the foliage was short (21-31 h). The time series
of (13)C in excess in the foliage was affected by the level of fertilization,
whereas the effect of throughfall exclusion was not significant. The velocity of
C transfer in the trunk (0.20-0.82 m h(-1)) was twice as high in +K trees than in
-K trees, with no significant effect of throughfall exclusion except for one +K
W tree labelled in the middle of the drought season that was exposed to a more
pronounced water stress (midday leaf water potential of -2.2 MPa). Our results
suggest that besides reductions in photosynthetic C supply and in C demand by
sink organs, the lower velocity under K deficiency is due to a lower cross
sectional area of the sieve tubes, whereas an increase in phloem sap viscosity is
more likely limiting phloem transport under drought. In all treatments, 10 times
less (13)C was recovered in inner bark extracts at the bottom of the trunk when
compared with the base of the crown, suggesting that a large part of the labelled
assimilates has been exported out of the phloem and replaced by unlabelled C.
This supports the 'leakage-retrieval mechanism' that may play a role in
maintaining the pressure gradient between source and sink organs required to
sustain high velocity of phloem transport in tall trees.
PMID- 26423336
TI - Root tip morphology, anatomy, chemistry and potential hydraulic conductivity vary
with soil depth in three temperate hardwood species.
AB - Root traits in morphology, chemistry and anatomy are important to root
physiological functions, but the differences between shallow and deep roots have
rarely been studied in woody plants. Here, we selected three temperate hardwood
species, Juglans mandshurica Maxim., Fraxinus mandschurica Rupr. and
Phellodendron amurense Rupr., in plantations in northeastern China and measured
morphological, anatomical and chemical traits of root tips (i.e., the first-order
roots) at surface (0-10 cm) and subsurface (20-30 cm) soil layers. The objectives
of this study were to identify how those traits changed with soil depth and to
reveal potential functional differences. The results showed that root diameters
in deep root tips were greater in J. mandshurica and F. mandschurica, but smaller
in P. amurense. However, root stele diameter and the ratio of stele to root
diameter in the subsurface layer were consistently greater in all three species,
which may enhance their abilities to penetrate into soil. All deep roots
exhibited lower tissue nitrogen concentration and respiration rate, which were
possibly caused by lower nutrient availability in the subsurface soil layer.
Significant differences between shallow and deep roots were observed in xylem
structure, with deep roots having thicker stele, wider maximum conduit and
greater number of conduits per stele. Compared with shallow roots, the
theoretical hydraulic conductivities in deep roots were enhanced by 133% (J.
mandshurica), 78% (F. mandschurica) and 217% (P. amurense), respectively,
indicating higher efficiency of transportation. Our results suggest that trees'
root tip anatomical structure and physiological activity vary substantially with
soil environment.
PMID- 26423337
TI - A Surface Plasmon Resonance Spectroscopy Method for Characterizing Small-Molecule
Binding to Nerve Growth Factor.
AB - Small-molecule inhibitors have been previously investigated to identify possible
therapeutics for the treatment of chronic pain. In the present study, known nerve
growth factor (NGF) inhibitors identified by (125)I-NGF binding were
characterized using affinity and binding evaluations by surface plasmon resonance
(SPR) spectroscopy. A novel strategy for characterizing NGF inhibitors was used
to determine the binding affinity (KD) and saturation ability of each compound
with immobilized NGF. Seventy-four percent of compounds screened demonstrated a
positive binding event to NGF. A KD less than 10 MUM and a percent saturation
greater than 50% were used as thresholds to identify inhibitors that would
warrant further investigation. This study details for the first time a
methodology that can be used to directly characterize the binding event between
small-molecule inhibitors and NGF.
PMID- 26423338
TI - Construction of a Semisynthetic Human VH Single-Domain Antibody Library and
Selection of Domain Antibodies against alpha-Crystalline of Mycobacterium
tuberculosis.
AB - The use of human variable heavy (VH) domain antibodies has been on the rise due
to their small scaffold size and simple folding mechanism. A highly diverse
library is largely dependent on the diversity introduced within the
complementarity-determining region (CDR) cassettes. Here we introduced diversity
with the use of a single framework diversifying all three CDRs using tailored
codons consisting of degenerate trinucleotides (NNK). The length of the
degeneracy in the CDRs was also taken into consideration based on the most
frequently occurring length of CDRs and the canonical confirmation for each
antibody subfamily. The semisynthetic human VH domain genes were assembled in a
single pot using a temperature cascading process. The affinity selection process
with Mycobacterium tuberculosis (MTb) alpha-crystalline was done using a
semiautomated process. Enrichment of target-specific clones was observed with
successful identification of monoclonal VH domain antibodies for MTb alpha
crystalline. In short, the semisynthetic library generated was able to select
monoclonal VH domain antibodies against full MTb alpha-crystalline protein with
complete semisynthetic CDRs displayed on a single scaffold. The library has the
potential to be applied for the isolation of antibodies against other pathogenic
proteins.
PMID- 26423339
TI - Screening and Identification of a Phage Display Derived Peptide That Specifically
Binds to the CD44 Protein Region Encoded by Variable Exons.
AB - CD44, especially the isoforms with variable exons (CD44v), is a promising
biomarker for the detection of cancer. To develop a CD44v-specific probe, we
screened a 7-mer phage peptide library against the CD44v3-v10 protein using an
improved subtractive method. The consensus sequences with the highest frequency
(designated CV-1) emerged after four rounds of panning. The binding affinity and
specificity of the CV-1 phage and the synthesized peptide for the region of CD44
encoded by the variable exons were confirmed using enzyme-linked immunosorbent
assay and competitive inhibition assays. Furthermore, the binding of the CV-1
probe to gastric cancer cells and tissues was validated using immunofluorescence
and immunohistochemistry assays. CV-1 sensitively and specifically bound to CD44v
on cancer cells and tissues. Thus, CV-1 has the potential to serve as a promising
probe for cancer molecular imaging and target therapy.
PMID- 26423340
TI - Recent innovations in the USA National Cancer Institute-sponsored investigator
initiated Phase I and II anticancer drug development.
AB - Exciting recent advancements in deep-sequencing technology have enabled a rapid
and cost-effective molecular characterization of patient-derived tumor samples.
Incorporating these innovative diagnostic technologies into early clinical trials
could significantly propel implementation of precision medicine by identifying
genetic markers predictive of sensitivity to agents. It may also markedly
accelerate drug development and subsequent regulatory approval of novel agents.
Particularly noteworthy, a high-response rate in a Phase II trial involving a
biomarker-enriched patient cohort could result in a regulatory treatment approval
in rare histologies, which otherwise would not be a candidate for a large
randomized clinical trial. Furthermore, even if a trial does not meet its
statistical endpoint, tumors from a few responders should be molecularly
characterized as part of the new biomarker-mining processes. In order to
accommodate patient screening and accelerate the accrual process, institutions
conducting early clinical trials need to be a part of a multi-institution
clinical trials network. Future clinical trial design will incorporate new
biomarkers discovered by a 'phenotype-to-genotype' effort with an appropriate
statistical design. To help advance such changes, the National Cancer Institute
has recently reformed the existing early phase clinical trials network. A new
clinical trial network, the Experimental Therapeutics Clinical Trials Network (ET
CTN), was begun and, in addition to its pre-existing infrastructure, an up-to
date clinical trial registration system, clinical trial monitoring system
including electronic database and a central Institutional Review Board were
formed. Ultimately, these reforms support identifying the most appropriate
therapy for each tumor type by incorporating state-of-the-art molecular
diagnostic tools into early clinical trials.
PMID- 26423341
TI - Safety and efficacy of concurrent carboplatin plus radiotherapy for locally
advanced head and neck cancer patients ineligible for treatment with cisplatin.
AB - OBJECTIVE: Cisplatin-based chemoradiotherapy is the standard treatment for
patients with locally advanced squamous cell carcinoma of the head and neck.
However, patients with advanced age, renal, cardiac or neurogenic dysfunction
seem ineligible for cisplatin treatment. We evaluated the safety and efficacy of
concurrent carboplatin plus radiotherapy in patients ineligible for cisplatin
usage. METHODS: We retrospectively analyzed the records of 25 consecutive locally
advanced squamous cell carcinoma of the head and neck patients who received
concurrent carboplatin plus radiotherapy at Shizuoka Cancer Center between August
2006 and March 2014. Carboplatin was administered tri-weekly or weekly. RESULTS:
Patient characteristics were analyzed. The median age was 75 years (range, 54
82), male:female ratio, 24:1; performance status, 0-1 (23) or 2 (2); primary
tumor site, oropharynx (10), hypopharynx (12), larynx (1) or oral cavity (2);
Stage III (3), IVa (19) or IVb (3); induction chemotherapy, with (2) or without
(23); and a median creatinine clearance of 62 ml/min (range, 37-117). The main
reasons for choosing carboplatin were age (40%), renal impairment (36%) and
cardiac dysfunction (20%). All patients received a planned irradiation dose of 70
Gy. Median follow-up was 30.9 months. Complete response was observed 70%
patients. Median progression-free survival duration was 42.7 months. Median
overall survival could not be analyzed. The 2-year progression-free and overall
survival rates were 68 and 74%, respectively. The main toxicity Grade 3 or 4 was
oral mucositis (56%), thrombocytopenia (34%), neutropenia (28%) and infection
(24%). CONCLUSIONS: Concurrent carboplatin plus radiotherapy is tolerated and may
be an option in treating locally advanced squamous cell carcinoma of the head and
neck patients ineligible for treatment with cisplatin.
PMID- 26423342
TI - A novel risk stratification model, involving preoperative lymphocyte-monocyte
ratio and standard pathological factors, for overall survival in patients with
bladder cancer undergoing radical cystectomy.
AB - OBJECTIVE: To evaluate the ability of preoperative lymphocyte-monocyte ratio to
predict prognosis and determine post-operative risk stratification in patients
with bladder cancer undergoing radical cystectomy. METHODS: A retrospective
review of the 210 patients who had undergone radical cystectomy for bladder
cancer from 2006 to 2013 identified 181 patients with sufficient data to evaluate
the prognostic significance of the lymphocyte-monocyte ratio. Overall survival
was assessed by the Kaplan-Meier method. The association of clinicopathological
findings with overall survival was evaluated by a multivariate Cox proportional
model, and a novel risk stratification model to predict prognosis was
established. RESULTS: Median follow-up after radical cystectomy was 6.0 years.
The 5-year overall survival rate was significantly lower for patients with low
than high lymphocyte-monocyte ratio (27.6 vs 80.7%, P < 0.001). Multivariable
analyses showed that pT >=2, pN >=1, positive margins and low lymphocyte-monocyte
ratio were independent predictors of overall survival. A post-operative risk
stratification model using these factors showed significant differences among the
three subgroups (low, intermediate and high risk) with a concordance index of
0.84. The 5-year overall survival rates in patients at low, intermediate and high
risk were 85.4, 45.5 and 0%, respectively (P < 0.001). CONCLUSIONS: Preoperative
lymphocyte-monocyte ratio, pathological tumor and lymph node stage and positive
margins are significantly associated with overall survival in patients who have
undergone radical cystectomy for bladder cancer.
PMID- 26423344
TI - Cortical hyperostosis as a side-effect of prolonged use of prostaglandins.
AB - Cortical hyperostosis is a very uncommon side-effect of prolonged prostaglandin
therapy with distinctive radiological signs that may be accompanied by painful
swelling of the limbs and responds rapidly to withdrawal of therapy.
PMID- 26423343
TI - Retinotopic organization of extrastriate cortex in the owl monkey--dorsal and
lateral areas.
AB - Dense retinotopy data sets were obtained by microelectrode visual receptive field
mapping in dorsal and lateral visual cortex of anesthetized owl monkeys. The
cortex was then physically flatmounted and stained for myelin or cytochrome
oxidase. Retinotopic mapping data were digitized, interpolated to a uniform grid,
analyzed using the visual field sign technique-which locally distinguishes mirror
image from nonmirror image visual field representations-and correlated with the
myelin or cytochrome oxidase patterns. The region between V2 (nonmirror) and MT
(nonmirror) contains three areas-DLp (mirror), DLi (nonmirror), and DLa/MTc
(mirror). DM (mirror) was thin anteroposteriorly, and its reduced upper field
bent somewhat anteriorly away from V2. DI (nonmirror) directly adjoined V2
(nonmirror) and contained only an upper field representation that also adjoined
upper field DM (mirror). Retinotopy was used to define area VPP (nonmirror),
which adjoins DM anteriorly, area FSTd (mirror), which adjoins MT
ventrolaterally, and TP (mirror), which adjoins MT and DLa/MTc dorsoanteriorly.
There was additional retinotopic and architectonic evidence for five more
subdivisions of dorsal and lateral extrastriate cortex-TA (nonmirror), MSTd
(mirror), MSTv (nonmirror), FSTv (nonmirror), and PP (mirror). Our data appear
quite similar to data from marmosets, though our field sign-based areal
subdivisions are slightly different. The region immediately anterior to the
superiorly located central lower visual field V2 varied substantially between
individuals, but always contained upper fields immediately touching lower visual
field V2. This region appears to vary even more between species. Though we
provide a summary diagram, given within- and between-species variation, it should
be regarded as a guide to parsing complex retinotopy rather than a literal
representation of any individual, or as the only way to agglomerate the complex
mosaic of partial upper and lower field, mirror- and nonmirror-image patches into
areas.
PMID- 26423345
TI - A Bayesian approach for inducing sparsity in generalized linear models with multi
category response.
AB - BACKGROUND: The dimension and complexity of high-throughput gene expression data
create many challenges for downstream analysis. Several approaches exist to
reduce the number of variables with respect to small sample sizes. In this study,
we utilized the Generalized Double Pareto (GDP) prior to induce sparsity in a
Bayesian Generalized Linear Model (GLM) setting. The approach was evaluated using
a publicly available microarray dataset containing 99 samples corresponding to
four different prostate cancer subtypes. RESULTS: A hierarchical Sparse Bayesian
GLM using GDP prior (SBGG) was developed to take into account the progressive
nature of the response variable. We obtained an average overall classification
accuracy between 82.5% and 94%, which was higher than Support Vector Machine,
Random Forest or a Sparse Bayesian GLM using double exponential priors.
Additionally, SBGG outperforms the other 3 methods in correctly identifying pre
metastatic stages of cancer progression, which can prove extremely valuable for
therapeutic and diagnostic purposes. Importantly, using Geneset Cohesion Analysis
Tool, we found that the top 100 genes produced by SBGG had an average functional
cohesion p-value of 2.0E-4 compared to 0.007 to 0.131 produced by the other
methods. CONCLUSIONS: Using GDP in a Bayesian GLM model applied to cancer
progression data results in better subclass prediction. In particular, the method
identifies pre-metastatic stages of prostate cancer with substantially better
accuracy and produces more functionally relevant gene sets.
PMID- 26423346
TI - Enantiomeric switching of chiral metamaterial for terahertz polarization
modulation employing vertically deformable MEMS spirals.
AB - Active modulation of the polarization states of terahertz light is indispensable
for polarization-sensitive spectroscopy, having important applications such as
non-contact Hall measurements, vibrational circular dichroism measurements and
anisotropy imaging. In the terahertz region, the lack of a polarization modulator
similar to a photoelastic modulator in the visible range hampers expansion of
such spectroscopy. A terahertz chiral metamaterial has a huge optical activity
unavailable in nature; nevertheless, its modulation is still challenging. Here we
demonstrate a handedness-switchable chiral metamaterial for polarization
modulation employing vertically deformable Micro Electro Mechanical Systems.
Vertical deformation of a planar spiral by a pneumatic force creates a three
dimensional spiral. Enantiomeric switching is realized by selecting the
deformation direction, where the polarity of the optical activity is altered
while maintaining the spectral shape. A polarization rotation as high as 28
degrees is experimentally observed, thus providing a practical and compact
polarization modulator for the terahertz range.
PMID- 26423347
TI - Bootstrap percolation on spatial networks.
AB - Bootstrap percolation is a general representation of some networked activation
process, which has found applications in explaining many important social
phenomena, such as the propagation of information. Inspired by some recent
findings on spatial structure of online social networks, here we study bootstrap
percolation on undirected spatial networks, with the probability density function
of long-range links' lengths being a power law with tunable exponent. Setting the
size of the giant active component as the order parameter, we find a parameter
dependent critical value for the power-law exponent, above which there is a
double phase transition, mixed of a second-order phase transition and a hybrid
phase transition with two varying critical points, otherwise there is only a
second-order phase transition. We further find a parameter-independent critical
value around -1, about which the two critical points for the double phase
transition are almost constant. To our surprise, this critical value -1 is just
equal or very close to the values of many real online social networks, including
LiveJournal, HP Labs email network, Belgian mobile phone network, etc. This work
helps us in better understanding the self-organization of spatial structure of
online social networks, in terms of the effective function for information
spreading.
PMID- 26423348
TI - Translating CESD-20 and PHQ-9 Scores to PROMIS Depression.
AB - This study examined the accuracy of depression cross-walk tables in a sample of
people with multiple sclerosis (MS). The tables link scores of two commonly used
depression measures to the Patient Reported Outcome Measurement Information
System Depression (PROMIS-D) scale metric. We administered the 8-item PROMIS-D
(Short-Form 8b; PROMIS-D-8), the 20-item Center for Epidemiologic Studies
Depression Scale (CESD-20), and the 9-item Patient Health Questionnaire (PHQ-9)
to 459 survey participants with MS. We examined correlations between actual
PROMIS-D-8 scores and the scores predicted by cross-walks based on PHQ-9 and CESD
20 scores. Intraclass correlation coefficients were used to assess
correspondence. Consistency in severity classification was also calculated.
Finally, we used Bland-Altman plots to graphically examine the levels of
agreement. The correlations between actual and cross-walked PROMIS-D-8 scores
were strong (CESD-20 = .82; PHQ-9 = .74). The intraclass correlation was moderate
(.77). Participants were consistently classified as having or not having at least
moderate depressive symptoms by both actual and cross-walked scores derived from
the CESD-20 (90%) and PHQ-9 (85%). Bland-Altman plots suggested the smaller
differences between actual and cross-walked scores with greater-than-average
depression severity. PROMIS cross-walk tables can be used to translate depression
scores of people with MS to the PROMIS-D metric, promoting continuity with
previous research.
PMID- 26423349
TI - Representation of the Cattell-Horn-Carroll Theory of Cognitive Abilities in the
Factor Structure of the Dutch-Language Version of the WAIS-IV.
AB - The Cattell-Horn-Carroll (CHC) theory of cognitive abilities has been guiding in
the revision of the Wechsler Adult Intelligence Scale-Fourth edition (WAIS-IV).
Especially the measurement of fluid reasoning (Gf) is improved. A total of five
CHC abilities are included in the WAIS-IV subtests. Using confirmatory factor
analysis, a five-factor model based on these CHC abilities is evaluated and
compared with the four index scores in the Dutch-language version of the WAIS-IV.
Both models demonstrate moderate fit, preference is given to the five-factor CHC
model both on statistical and theoretical grounds. Evaluation of the WAIS-IV
according to CHC terminology enhances uniformity, and can be important when
interpreting possible sources of index discrepancies. To optimally assemblage CHC
and WAIS-IV, more knowledge of the interaction of abilities is needed. This can
be done by incorporating intelligence testing in neuropsychological assessment.
Using this functional approach contributes to a better understanding of an
individual's cognitive profile.
PMID- 26423350
TI - Improving the Detection of Feigned Knowledge Deficits in Defendants Adjudicated
Incompetent to Stand Trial.
AB - Malingering is relatively common in criminal forensic evaluations as base rates
of malingering have ranged from 20% to 30%. Given that the most prevalent
criminal forensic evaluation is the assessment of competency to stand trial, the
assessment of feigning during competency evaluations is necessary for accurate
findings. Most of the response style literature focuses on feigning mental health
symptoms, but in competency evaluations, individuals may attempt to feign legal
knowledge deficits in order to be found incompetent to stand trial. The current
investigation includes two studies: 195 students instructed to simulate feigned
mental illness or incompetence to stand trial and one using a sample of 130 state
psychiatric hospital residents who had been adjudicated incompetent to stand
trial. The purpose of the study was to evaluate the Inventory of Legal
Knowledge's (ILK; Musick & Otto, 2010) ability to detect individuals who are
feigning legal knowledge deficits. Classification utility statistics, including
sensitivity, specificity, positive predictive power, and negative predictive
power are provided for each cut-score on the ILK beginning with a cut-score of 24
(which is the lower end of the range of chance) are provided. The current cut
score of 47 provided in the professional manual of the ILK was shown to create a
large number of false positives and suggests that modifications to this cut-score
are required.
PMID- 26423351
TI - Longitudinal Measurement Invariance of Beck Depression Inventory-II in Early
Adolescents.
AB - This study explored the longitudinal measurement invariance in the Beck
Depression Inventory-II (BDI-II) in early adolescents (junior high school
students). The participants were 730 early adolescents (330 boys and 400 girls),
who were followed up over 3 years (in six waves). To reduce the size of
longitudinal model and verify the stability of the findings, the Fall and Spring
series data sets were analyzed separately. Each series includes three waves of
data with about 1-year apart. It was found that the three-factor model (Negative
Attitude, Performance Difficulty, and Somatic Elements) best fitted the data.
Results of both data sets provided support for the longitudinal measurement
invariance (threshold invariance) of the three-factor model, suggesting that the
BDI-II measured the same construct over 3 years. The study also examined the
category function of the BDI-II on the basis of the pattern of threshold
estimates. Finally, the implications of the findings on the continuing use of the
BDI-II are discussed.
PMID- 26423352
TI - The protein kinase 2 inhibitor tetrabromobenzotriazole protects against renal
ischemia reperfusion injury.
AB - Protein kinase 2 (CK2) activation was reported to enhance reactive oxygen species
production and activate the nuclear factor kappaB (NF-kappaB) pathway. Because
oxidative stress and inflammation are critical events for tissue destruction
during ischemia reperfusion (I/R), we sought to determine whether CK2 was
important in the renal response to I/R. Mice underwent 25 min of renal ischemia
and were then reperfused. We confirmed an increased expression of CK2alpha during
the reperfusion period, while expression of CK2beta remained consistent. We
administered tetrabromobenzotriazole (TBBt), a selective CK2alpha inhibitor
before inducing I/R injury. Mice subjected to I/R injury showed typical patterns
of acute kidney injury; blood urea nitrogen and serum creatinine levels, tubular
necrosis and apoptosis, inflammatory cell infiltration and proinflammatory
cytokine production, and oxidative stress were markedly increased when compared
to sham mice. However, pretreatment with TBBt abolished these changes and
improved renal function and architecture. Similar renoprotective effects of
CK2alpha inhibition were observed for emodin. Renoprotective effects of CK2alpha
inhibition were associated with suppression of NF-kappaB and mitogen activated
protein kinase (MAPK) pathways. Taken together, these results suggest that
CK2alpha mediates proapoptotic and proinflammatory signaling, thus the CK2alpha
inhibitor may be used to prevent renal I/R injuries observed in clinical
settings.
PMID- 26423354
TI - Authors' reply.
PMID- 26423353
TI - An optogenetic system for interrogating the temporal dynamics of Akt.
AB - The dynamic activity of the serine/threonine kinase Akt is crucial for the
regulation of diverse cellular functions, but the precise spatiotemporal control
of its activity remains a critical issue. Herein, we present a photo-activatable
Akt (PA-Akt) system based on a light-inducible protein interaction module of
Arabidopsis thaliana cryptochrome2 (CRY2) and CIB1. Akt fused to CRY2phr, which
is a minimal light sensitive domain of CRY2 (CRY2-Akt), is reversibly activated
by light illumination in several minutes within a physiological dynamic range and
specifically regulates downstream molecules and inducible biological functions.
We have generated a computational model of CRY2-Akt activation that allows us to
use PA-Akt to control the activity quantitatively. The system provides evidence
that the temporal patterns of Akt activity are crucial for generating one of the
downstream functions of the Akt-FoxO pathway; the expression of a key gene
involved in muscle atrophy (Atrogin-1). The use of an optical module with
computational modeling represents a general framework for interrogating the
temporal dynamics of biomolecules by predictive manipulation of optogenetic
modules.
PMID- 26423355
TI - Long-term manure amendments reduced soil aggregate stability via redistribution
of the glomalin-related soil protein in macroaggregates.
AB - Glomalin-related soil protein (GRSP) contributes to the formation and maintenance
of soil aggregates, it is however remains unclear whether long-term intensive
manure amendments alter soil aggregates stability and whether GRSP regulates
these changes. Based on a three-decade long fertilization experiment in northeast
China, this study examined the impact of long-term manure input on soil organic
carbon (SOC), total and easily extractable GRSP (GRSPt and GRSPe) and their
respective allocations in four soil aggregates (>2000 MUm; 2000-250 MUm; 250-53
MUm; and <53 MUm). The treatments include no fertilization (CK), low and high
manure amendment (M1, M2), chemical nitrogen, phosphorus and potassium
fertilizers (NPK), and combined manure and chemical fertilizers (NPKM1, NPKM2).
Though SOC, GRSPe and GRSPt in soil and SOC in each aggregate generally increased
with increasing manure input, GRSPt and GRSPe in each aggregate showed varying
changes with manure input. Both GRSP in macroaggregates (2000-250 MUm) were
significantly higher under low manure input, a pattern consistent with changes in
soil aggregate stability. Constituting 38~49% of soil mass, macroaggregates
likely contributed to the nonlinear changes of aggregate stability under manure
amendments. The regulatory process of GRSP allocations in soil aggregates has
important implications for manure management under intensive agriculture.
PMID- 26423356
TI - Synergistic algicidal effect and mechanism of two diketopiperazines produced by
Chryseobacterium sp. strain GLY-1106 on the harmful bloom-forming Microcystis
aeruginosa.
AB - A potent algicidal bacterium isolated from Lake Taihu, Chryseobacterium sp.
strain GLY-1106, produces two algicidal compounds: 1106-A (cyclo(4-OH-Pro-Leu))
and 1106-B (cyclo(Pro-Leu)). Both diketopiperazines showed strong algicidal
activities against Microcystis aeruginosa, the dominant bloom-forming
cyanobacterium in Lake Taihu. Interestingly, these two algicidal compounds
functioned synergistically. Compared with individual treatment, combined
treatment with cyclo(4-OH-Pro-Leu) and cyclo(Pro-Leu) significantly enhanced
algicidal activity, accelerated the increase in intracellular reactive oxygen
species (ROS) levels in M. aeruginosa, and further decreased the activities of
antioxidases, effective quantum yield and maximal electron transport rate of M.
aeruginosa. The results also showed that the algicidal characteristics of cyclo(4
OH-Pro-Leu) are distinct from those of cyclo(Pro-Leu). Cyclo(4-OH-Pro-Leu) mainly
interrupted the flux of electron transport in the cyanobacterial photosynthetic
system, whereas cyclo(Pro-Leu) mainly inhibited the activity of cyanobacterial
intracellular antioxidases. A possible algicidal mechanism for the synergism
between cyclo(4-OH-Pro-Leu) and cyclo(Pro-Leu) is proposed, which is in
accordance with their distinct algicidal characteristics in individual and
combined treatment. These findings suggest that synergism between algicidal
compounds might be used as an effective strategy for the future control of
Microcystis blooms.
PMID- 26423357
TI - Dietary intake and food sources of choline in European populations.
AB - Choline is an important nutrient for humans. Choline intake of the European
population was assessed considering the European Food Safety Authority European
Comprehensive Food Consumption Database and the United States Department of
Agriculture Nutrient Database. Average choline intake ranges were 151-210 mg/d
among toddlers (1 to <=3 years old), 177-304 mg/d among other children (3 to <=10
years old), 244-373 mg/d among adolescents (10 to <=18 years old), 291-468 mg/d
among adults (18 to <=65 years old), 284-450 mg/d among elderly people (65 to
<=75 years old) and 269-444 mg/d among very elderly people (>=75 years old). The
intakes were higher among males compared with females, mainly due to larger
quantities of food consumed per day. In most of the population groups considered,
the average choline intake was below the adequate intake (AI) set by the
Institute of Medicine in the USA. The main food groups contributing to choline
intake were meat, milk, grain, egg and their derived products, composite dishes
and fish. The main limitations of this study are related to the absence of
choline composition data of foods consumed by the European population and the
subsequent assumption made to assess their intake levels. Given the definition of
AI, no conclusion on the adequacy of choline intake can be drawn for most
European population groups. Such results improve the knowledge on choline intake
in Europe that could be further refined by the collection of choline composition
data for foods as consumed in Europe.
PMID- 26423358
TI - Dinucleotide circular codes and bijective transformations.
AB - The presence of circular codes in mRNA coding sequences is postulated to be
involved in informational mechanisms aimed at detecting and maintaining the
normal reading frame during protein synthesis. Most of the recent research is
focused on trinucleotide circular codes. However, also dinucleotide circular
codes are important since dinucleotides are ubiquitous in genomes and associated
to important biological functions. In this work we adopt the group theoretic
approach used for trinucleotide codes in Fimmel et al. (2015) to study
dinucleotide circular codes and highlight their symmetry properties. Moreover, we
characterize such codes in terms of n-circularity and provide a graph
representation that allows to visualize them geometrically. The results establish
a theoretical framework for the study of the biological implications of
dinucleotide circular codes in genomic sequences.
PMID- 26423359
TI - Alternative adaptive immunity strategies: coelacanth, cod and shark immunity.
AB - The advent of high throughput sequencing has permitted to investigate the genome
and the transcriptome of novel non-model species with unprecedented depth. This
technological advance provided a better understanding of the evolution of
adaptive immune genes in gnathostomes, revealing several unexpected features in
different fish species which are of particular interest. In the present paper, we
review the current understanding of the adaptive immune system of the coelacanth,
the elephant shark and the Atlantic cod. The study of coelacanth, the only living
extant of the long thought to be extinct Sarcopterygian lineage, is fundamental
to bring new insights on the evolution of the immune system in higher
vertebrates. Surprisingly, coelacanths are the only known jawed vertebrates to
lack IgM, whereas two IgD/W loci are present. Cartilaginous fish are of great
interest due to their basal position in the vertebrate tree of life; the genome
of the elephant shark revealed the lack of several important immune genes related
to T cell functions, which suggest the existence of a primordial set of TH1-like
cells. Finally, the Atlantic cod lacks a functional major histocompatibility II
complex, but balances this evolutionary loss with the expansion of specific gene
families, including MHC I, Toll-like receptors and antimicrobial peptides.
Overall, these data point out that several fish species present an unconventional
adaptive immune system, but the loss of important immune genes is balanced by
adaptive evolutionary strategies which still guarantee the establishment of an
efficient immune response against the pathogens they have to fight during their
life.
PMID- 26423360
TI - Trafficking regulates the subcellular distribution of voltage-gated sodium
channels in primary sensory neurons.
AB - Voltage-gated sodium channels (Navs) comprise at least nine pore-forming alpha
subunits. Of these, Nav1.6, Nav1.7, Nav1.8 and Nav1.9 are the most frequently
studied in primary sensory neurons located in the dorsal root ganglion and are
mainly localized to the cytoplasm. A large pool of intracellular Navs raises the
possibility that changes in Nav trafficking could alter channel function. The
molecular mediators of Nav trafficking mainly consist of signals within the Navs
themselves, interacting proteins and extracellular factors. The surface
expression of Navs is achieved by escape from the endoplasmic reticulum and
proteasome degradation, forward trafficking and plasma membrane anchoring, and it
is also regulated by channel phosphorylation and ubiquitination in primary
sensory neurons. Axonal transport and localization of Navs in afferent fibers
involves the motor protein KIF5B and scaffold proteins, including contactin and
PDZ domain containing 2. Localization of Nav1.6 to the nodes of Ranvier in
myelinated fibers of primary sensory neurons requires node formation and the
submembrane cytoskeletal protein complex. These findings inform our understanding
of the molecular and cellular mechanisms underlying Nav trafficking in primary
sensory neurons.
PMID- 26423361
TI - Zfp553 Is Essential for Maintenance and Acquisition of Pluripotency.
AB - Pluripotent cells are promising tools in the arena of regenerative medicine. For
many years, research efforts have been directed toward uncovering the underlying
mechanisms that govern the pluripotent state and this involves identifying new
pluripotency-associated factors. Zinc finger protein 553 (Zfp553) has been
hypothesized to be one such factor because of its predominant expression in inner
cell mass of the mouse early embryo. In this study, we have identified Zfp553 as
a regulator of pluripotency. Zfp553 knockdown downregulates pluripotency markers
and triggers differentiation in mouse embryonic stem cells (mESCs). Further
investigation revealed that Zfp553 regulates pluripotency in mESCs through the
transcriptional activation of Pou5f1 and Nanog. Microarray results revealed that
depletion of Zfp553 downregulates many pluripotency genes, as well as genes
associated with metabolism-related processes. ChIP-sequencing (ChIP-seq) depicted
the genomic binding sites of Zfp553 in mESCs and its binding motif. In addition,
we found that depletion of Zfp553 could impair somatic cell reprogramming,
evidenced by reduced reprogramming efficiency and cell viability. Together, our
preliminary findings provide novel insights to a newly identified pluripotency
factor Zfp553 and its role in pluripotency regulation.
PMID- 26423362
TI - Retinal development impairment and degenerative alterations in adult rats
subjected to post-natal malnutrition.
AB - BACKGROUND: The early stages of central nervous system (CNS) development are
extremely important. Key events such as neurogenesis, gliogenesis,
synaptogenesis, and ontogenesis occur. Malnutrition promotes alterations in CNS
development, including the retinal development. During retinal development,
malnutrition can induce a delay in some important events, such as
neurotransmitter expression and neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS:
Postpartum Wistar rats were fed either a commercial diet or a multideficient
diet. Pups were breastfed by these rats, and from PND21 were kept with the same
diet until PND45. We investigated the effects of malnutrition on adult retinal
tissue with regard to (1) endogenous gamma-amino butyric acid (GABA) release
induced by excitatory amino acids (EAAs) and (2) the expression of cellular
markers related to degenerative events, such as reactive gliosis, microglial
activation, cell proliferation and cell death. Endogenous GABA release induced by
EAAs was higher in the retina of malnourished rats. The Muller cell population
was reduced and displayed alterations in their phenotype profile compatible with
reactive gliosis. The expression of glutamine synthetase and markers of cellular
proliferation were higher in the retina of malnourished rats. Additionally,
retinal dysplasia-like structures were present, indicating disturbance in the
cell cycle machinery. CONCLUSION/SIGNIFICANCE: The current study provides
evidence that the adult retina shows degenerative processes induced by long-term
malnutrition during the postnatal development. These findings have high clinical
significance with regard to the identification of possible targets for
interventions in malnourished patients.
PMID- 26423363
TI - From perceived autonomy support to intentional behaviour: Testing an integrated
model in three healthy-eating behaviours.
AB - A motivational model integrating self-determination theory, the theory of planned
behaviour, and the health action process approach was tested in three samples in
three behavioural contexts: fruit and vegetable, breakfast, and snack
consumption. Perceived support for autonomous (self-determined) forms of
motivation from parents and autonomous motivation from self-determination theory
were hypothesised to predict intention and behaviour indirectly via the mediation
of attitude and perceived behavioural control from the theory of planned
behaviour. It was also expected that planning strategies would mediate the effect
of intention on behaviour. Relations in the proposed models were expected to be
similar across the behaviours. A two-wave prospective design was adopted. Three
samples of high-school students (total N = 1041; 59.60% female; M age = 17.13
years +/- 1.57) completed measures of perceived autonomy support, autonomous
motivation, theory of planned behaviour constructs, planning strategies and
behaviour for each of the three behavioural contexts. Three months later, 816
participants (62,24% female; M age: 17.13 years, SD = 1.58) of the initial sample
self-reported their behaviour referred to the previous three months. Structural
equation models provided support for the key hypothesised effects of the proposed
model for the three health-related behaviours. Two direct effects were
significantly different across the three behaviours: the effect of perceived
autonomy support on perceived behavioural control and the effect of attitude on
intention. In addition, planning strategies mediated the effect of intention on
behaviour in fruit and vegetable sample only. Findings extend knowledge of the
processes by which psychological antecedents from the theories affect energy
balance related behaviours.
PMID- 26423365
TI - Quercetin interacts with Cry1Ac protein to affect larval growth and survival of
Helicoverpa armigera.
AB - BACKGROUND: Bt cotton has been widely planted in China for over a decade to
control H. armigera, but field surveys indicate increasing resistance in the
pest. It has been speculated that accumulating plant secondary compounds in
mature cotton may interact with Bt toxins and affect the toxicity of Bt to H.
armigera. RESULTS: Both quercetin, one of the main flavonoids in cotton, and the
Bt toxin Cry1Ac protein had significant negative effects on the growth,
development and survival of H. armigera when added singly to artificial diet, but
their effects were inhibited when added in combination. Quercetin was
antagonistic to Cry1Ac toxicity at all tested concentrations. CONCLUSION: The
accumulation of quercetin might be one factor contributing to the reduced
toxicity of mature Bt cotton plants to H. armigera, and could partially explain
the reduced efficacy of Cry1Ac in controlling this pest in the field. (c) 2015
Society of Chemical Industry.
PMID- 26423364
TI - Item banks for substance use from the Patient-Reported Outcomes Measurement
Information System (PROMIS((r))): Severity of use and positive appeal of use.
AB - BACKGROUND: Two item banks for substance use were developed as part of the
Patient-Reported Outcomes Measurement Information System (PROMIS((r))): severity
of substance use and positive appeal of substance use. METHODS: Qualitative item
analysis (including focus groups, cognitive interviewing, expert review, and item
revision) reduced an initial pool of more than 5300 items for substance use to
119 items included in field testing. Items were written in a first-person, past
tense format, with 5 response options reflecting frequency or severity. Both 30
day and 3-month time frames were tested. The calibration sample of 1336
respondents included 875 individuals from the general population (ascertained
through an internet panel) and 461 patients from addiction treatment centers
participating in the National Drug Abuse Treatment Clinical Trials Network.
RESULTS: Final banks of 37 and 18 items were calibrated for severity of substance
use and positive appeal of substance use, respectively, using the two-parameter
graded response model from item response theory (IRT). Initial calibrations were
similar for the 30-day and 3-month time frames, and final calibrations used data
combined across the time frames, making the items applicable with either
interval. Seven-item static short forms were also developed from each item bank.
CONCLUSIONS: Test information curves showed that the PROMIS item banks provided
substantial information in a broad range of severity, making them suitable for
treatment, observational, and epidemiological research in both clinical and
community settings.
PMID- 26423366
TI - Prevalence and predictors of patient no-shows to outpatient endoscopic procedures
scheduled with anesthesia.
AB - BACKGROUND: Demand for endoscopic procedures scheduled with anesthesia is
increasing and no-show to appointments carries significant patient health and
financial impact, yet little is known about predictors of no-show. METHODS: We
performed a 16-month retrospective observational cohort study of patients
scheduled for outpatient endoscopy with anesthesia at a county hospital serving
the safety-net healthcare system of San Francisco. Multivariate logistic
regression analysis was performed to evaluate associations between attendance and
predictors of no-show. RESULTS: In total, 511 patients underwent endoscopy with
anesthesia during the study period. Twenty-seven percent of patients failed to
attend an appointment and were considered "no-show". In multivariate analysis,
higher no-show rates were associated with patients with a prior history of no
show (odds ratio [OR] 6.4; 95% confidence interval [CI], 2.4- 17.5), those with
active substance abuse within the past year (OR 2.2; 95% CI 1.4-3.6), those with
heavy prescription opioids/benzodiazepines use (OR 1.6; 95% CI 1.0-2.6) and
longer wait-times (OR 1.05; 95% CI 1.00-1.09). Inversely associated with patient
no-show were active employment (OR 0.38; 95% CI 0.18-0.81), patients who attended
a pre-operative appointment with an anesthesiologist (OR 0.52; CI 0.32-0.85), and
those undergoing an advanced endoscopic procedure (OR 0.43; 95% CI 0.19-0.94).
CONCLUSION: In a safety-net healthcare population, behavioral and social
determinants of health, including missed appointments, active substance abuse,
homelessness, and unemployment are associated with no-shows to endoscopy with
anesthesia.
PMID- 26423367
TI - An end to AIDS is possible, but not without an end to HIV.
PMID- 26423368
TI - Treatment of hepatitis C in patients with HIV.
PMID- 26423369
TI - When is the best time to initiate antiretroviral therapy?
PMID- 26423370
TI - Registries and syndemics: untapped potential for global health.
PMID- 26423371
TI - Light and shade behind the opt-out system for the HIV screening.
PMID- 26423372
TI - Light and shade behind the opt-out system for the HIV screening.
PMID- 26423373
TI - Light and shade behind the opt-out system for the HIV screening - Authors' reply.
PMID- 26423374
TI - Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients
with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non
randomised, open-label trial.
AB - BACKGROUND: Hepatitis C virus (HCV) infection is a leading cause of morbidity and
mortality in patients with HIV-1. The C-EDGE CO-INFECTION study assessed the
efficacy, safety, and tolerability of grazoprevir (MK-5172) plus elbasvir (MK
8742) in patients with HCV and HIV co-infection. METHODS: In this uncontrolled,
non-randomised, phase 3, open-label, single-arm study, treatment-naive patients
with chronic HCV genotype 1, 4, or 6 infection and HIV co-infection, with or
without cirrhosis, were enrolled from 37 centres in nine countries across Europe,
the USA, and Australia. Patients were either naive to treatment with any
antiretroviral therapy (ART) or stable on ART for at least 8 weeks. All patients
received grazoprevir 100 mg plus elbasvir 50 mg in a fixed-dose combination
tablet once daily for 12 weeks. The primary endpoint was sustained virological
response (HCV RNA <15 IU/mL) 12 weeks after the end of therapy (SVR12). The
primary population for efficacy analyses was all patients who received at least
one dose of study treatment. This study is registered with ClinicalTrials.gov,
number NCT02105662. FINDINGS: Between June 11, 2014, and Aug 29, 2014, 218
patients were enrolled and received grazoprevir plus elbasvir for 12 weeks, all
of whom completed follow-up at week 12. SVR12 was achieved by 210 (96%) of 218
patients (95% CI 92.9-98.4). One patient did not achieve SVR12 because of a non
virological reason, and seven patients without cirrhosis relapsed (two
subsequently confirmed as reinfections). All 35 patients with cirrhosis achieved
SVR12. The most common adverse events were fatigue (29; 13%), headache (27; 12%),
and nausea (20; 9%). No patient discontinued treatment because of an adverse
event. Two patients receiving ART had transient HIV viraemia. INTERPRETATION:
This HCV treatment regimen seems to be effective and well tolerated for patients
co-infected with HIV with or without cirrhosis. These data are consistent with
previous trials of this regimen in the monoinfected population. This regimen
continues to be studied in phase 3 trials. FUNDING: Merck Sharp & Dohme Corp.
PMID- 26423375
TI - Nurse-led palliative care for HIV-positive patients taking antiretroviral therapy
in Kenya: a randomised controlled trial.
AB - BACKGROUND: People with HIV accessing antiretroviral therapy (ART) have
persistent physical, psychological, social, and spiritual problems, which are
associated with poor quality of life and treatment outcomes. We assessed the
effectiveness of a nurse-led palliative care intervention on patient-reported
outcomes. METHODS: We did this randomised controlled trial at a clinic in Kenya
for adults with HIV, established on ART, and reporting moderate-to-severe pain or
symptoms. We randomly assigned participants (1:1) either to a palliative care
intervention (including assessments of physical, emotional, and spiritual
wellbeing and quality of life) given six times over 4 months, or to usual care.
Participants and investigators were not masked to allocation. The primary outcome
was pain (scored on the African Palliative Care Association's African Palliative
Outcome Scale). This trial is registered with ClinicalTrials.gov, number
NCT01608802. FINDINGS: We screened 2070 patients, of whom we enrolled 120: 60
allocated to each group. In the control group, median pain score improved from
1.0 (IQR 0.0-2.0) at baseline to 5.0 (3.0-5.0) at 4 months; in the intervention
group, it improved from 1.0 (0.0-2.0) at baseline to 4.5 (3.0-5.0) at 4 months.
Compared with standard care, the intervention had no significant effect on pain
(coefficient -0.01, 95% CI -0.36 to 0.34, p=0.95). INTERPRETATION: A nurse-led
palliative care intervention was not effective in reducing pain. However, person
centred assessment and care delivered by staff who have received additional
training had positive effects on self-reported mental health related quality of
life and psychosocial wellbeing. FUNDING: Diana Princess of Wales Memorial Fund.
PMID- 26423377
TI - Associations between HIV and schizophrenia and their effect on HIV treatment
outcomes: a nationwide population-based cohort study in Denmark.
AB - BACKGROUND: Associations between HIV and schizophrenia in people with and without
substance use disorders and the effect on timeliness of HIV diagnosis,
antiretroviral therapy (ART), and treatment outcomes are poorly understood. We
aimed to assess the association between HIV and schizophrenia and the effect on
HIV treatment outcomes in people with and without substance use disorders.
METHODS: We did a population-based cohort study with data from nationwide
registries in Denmark to investigate the risk of schizophrenia after a diagnosis
of HIV and the risk of HIV after a diagnosis of schizophrenia, accounting for
substance misuse, timeliness of HIV diagnosis, and treatment success in relation
to schizophrenia. We selected the cohort from people born in Denmark between Jan
1, 1955, and Dec 31, 1995, who we followed up from their 16th birthday or Jan 1,
1995 (whichever occurred last) until their death, emigration from Denmark, onset
of schizophrenia, or Dec 31, 2011 (whichever came first). We estimated incidence
rate ratios (IRRs) with Poisson and Cox regression, with adjustment for calendar
period, and age and its interaction with sex. FINDINGS: We identified 2,786,286
individuals, of whom we included 2,646,154 people in analyses of risk of
schizophrenia diagnosis and 2,658,662 people in analyses of risk of HIV
diagnosis. In 35,353,633 person-years of follow up, HIV was associated with an
increased risk of schizophrenia (IRR 4.09, 95% CI 2.73-5.83) and acute psychosis
(7.15, 4.45-10.8); the IRR was highest within the first year of HIV diagnosis for
both disorders (8.24, 2.95-17.7 and 12.7, 3.15-32.9, respectively). Schizophrenia
was not associated with an increased risk of HIV in individuals without substance
misuse disorders (IRR 1.42, 95% CI 0.81-2.27). The risk of schizophrenia in
individuals with HIV decreased after ART (IRR 0.53, 0.32-0.87). The risk of acute
psychosis did not differ between HIV-infected individuals receiving
antiretroviral regimens with and without efavirenz (IRR 0.70, 95% CI 0.32-1.54).
We recorded no differences in CD4 cell counts, time to ART, or viral suppression
between individuals with schizophrenia with HIV and those without schizophrenia
when substance use was taken into account. Between 1999 and 2011, the mortality
rate ratio comparing HIV-infected individuals with schizophrenia with HIV
negative individuals without schizophrenia was 25.8 (95% CI 18.8-34.3).
INTERPRETATION: Our findings emphasise the need for interventions to prevent HIV
in people with schizophrenia, especially for those with substance use disorders,
and for accessible mental health services for individuals with HIV. FUNDING:
Stanley Medical Research Institute, Lundbeck Foundation, Preben and Anna Simonsen
Fund, Novo Nordisk Foundation, The Danish AIDS Foundation, and the Augustinus
Foundation.
PMID- 26423379
TI - Quadri F et al (Clin Infect Dis 2015; 60:1737-42).
PMID- 26423378
TI - Body image and weight control in South Africans 15 years or older: SANHANES-1.
AB - BACKGROUND: South African studies have suggested that differences in obesity
prevalence between groups may be partly related to differences in body image and
body size dissatisfaction. However, there has never been a national study that
measured body image and its relationship to weight control in the country. Hence,
the main aim of the study was to examine body image in relation to body mass
index and weight control in South Africa. METHODS: A cross-sectional survey and a
secondary analyses of data were undertaken for 6 411 South Africans (15+ years)
participating in the first South African National Health and Nutrition
Examination Survey. Body image was investigated in relation to weight status and
attempts to lose or gain weight. Data were analysed using STATA version 11.0.
Descriptive statistics are presented as counts (numbers), percentages, means,
standard error of means, and 95 % confidence intervals. Any differences in values
were considered to be significantly different if the confidence intervals did not
overlap. RESULTS: Overall, 84.5 % participants had a largely distorted body image
and 45.3 % were highly dissatisfied about their body size. Overweight and obese
participants under estimated their body size and desired to be thinner. On the
other hand, normal- and under-weight participants over estimated their body size
and desired to be fatter. Only 12.1 and 10.1 % of participants attempted to lose
or gain weight, respectively, mainly by adjusting dietary intake and physical
activity. DISCUSSION: Body mass index appears to influence body image and weight
adjustment in South Africa. CONCLUSIONS: South Africans at the extreme ends of
the body mass index range have a largely distorted body image and are highly
dissatisfied by it. This suggests a need for health education and beneficial
weight control strategies to halt the obesity epidemic in the country.
PMID- 26423380
TI - Butel MJ et al (Clin Infect Dis 2015; 61:1116-8).
PMID- 26423382
TI - HIV Infection: Still a Disease for Experts.
PMID- 26423381
TI - Nasal Skin Necrosis: An Unexpected New Finding in Severe Chikungunya Fever.
AB - Three adult Venezuelan patients with virologically confirmed Chikungunya fever,
who developed extensive acute nasal skin necrosis early in the course of a life
threatening illness characterized by shock and multiple organ dysfunction
syndrome, are discussed. One patient survived and fully recovered. Nasal necrosis
has not previously been associated with the disease.
PMID- 26423383
TI - The HIV Workforce in New York State: Does Patient Volume Correlate with Quality?
AB - BACKGROUND: Knowledge of care practices among clinicians who annually treat <20
human immunodeficiency virus (HIV)-positive patients with antiretroviral therapy
(ART) is insufficient, despite their number, which is likely to increase given
shifting healthcare policies. We analyze the practices, distribution and quality
of care provided by low-volume prescribers (LVPs) based on available data sources
in New York State. METHODS: We communicated with 1278 (66%) of the LVPs
identified through a statewide claims database to determine the circumstances
under which they prescribed ART in federal fiscal year 2009. We reviewed patient
records from 84 LVPs who prescribed ART routinely and compared their performance
with that of experienced clinicians practicing in established HIV programs.
RESULTS: Of the surveyed LVPs, 368 (29%) provided routine ambulatory care for
2323 persons living with HIV/AIDS, and 910 LVPs cited other reasons for
prescribing ART. Although the majority of LVPs (73%) practiced in New York City,
patients living upstate were more likely to be cared for by a LVP (odds ratio,
1.7; 95% confidence interval, 1.4-1.9). Scores for basic HIV performance
measures, including viral suppression, were significantly higher in established
HIV programs than for providers who wrote prescriptions for <20 persons living
with HIV/AIDS (P < .01). We estimate that 33% of New York State clinicians who
provide ambulatory HIV care are LVPs. CONCLUSIONS: Our findings suggest that the
quality of care associated with providers who prescribe ART for <20 patients is
lower than that provided by more experienced providers. Access to experienced
providers as defined by patient volume is an important determinant of delivering
high-quality care and should guide HIV workforce policy decisions.
PMID- 26423384
TI - Access and Quality of HIV-Related Point-of-Care Diagnostic Testing in Global
Health Programs.
AB - Access to point-of-care testing (POCT) improves patient care, especially in
resource-limited settings where laboratory infrastructure is poor and the bulk of
the population lives in rural settings. However, because of challenges in rolling
out the technology and weak quality assurance measures, the promise of human
immunodeficiency virus (HIV)-related POCT in resource-limited settings has not
been fully exploited to improve patient care and impact public health. Because of
these challenges, the Joint United Nations Programme on HIV/AIDS (UNAIDS), in
partnership with other organizations, recently launched the Diagnostics Access
Initiative. Expanding HIV programs, including the "test and treat" strategies and
the newly established UNAIDS 90-90-90 targets, will require increased access to
reliable and accurate POCT results. In this review, we examine various components
that could improve access and uptake of quality-assured POC tests to ensure
coverage and public health impact. These components include evaluation, policy,
regulation, and innovative approaches to strengthen the quality of POCT.
PMID- 26423385
TI - Standardizing 25-hydroxyvitamin D values from the Canadian Health Measures
Survey.
AB - BACKGROUND: The Canadian Health Measures Survey (CHMS) is an ongoing cross
sectional national survey that includes a measure of 25-hydroxyvitamin D
[25(OH)D] by immunoassay. For cycles 1 and 2, the collection period occurred
approximately every 2 y, with a new sample of ~5600 individuals. OBJECTIVE: The
goal was to standardize the original 25(OH)D CHMS values in cycles 1 and 2 to the
internationally recognized reference measurement procedures (RMPs) developed by
the US National Institute for Standards and Technology (NIST) and Ghent
University, Belgium. DESIGN: Standardization was accomplished by using a 2-step
procedure. First, serum samples corresponding to the original plasma samples were
remeasured by using the currently available immunoassay method. Second, 50 serum
samples with known 25(OH)D values assigned by the NIST and Ghent reference method
laboratories were measured by using the currently available immunoassay method.
The mathematical models for each step-i.e., 1) YCurrent = XOriginal and 2) YNIST
Ghent = XCurrent -were estimated by using Deming regression, and the 2 models
were solved to obtain a single equation for converting the "original" values to
NIST-Ghent RMP values. RESULTS: After standardization (cycles 1 and 2 combined),
the percentage of Canadians with 25(OH)D values <40 nmol/L increased from 16.4%
(original) to 19.4% (standardized), and values <50 nmol/L increased from 29.0%
(original) to 36.8% (standardized). The 25(OH)D standardized distributions
(cycles 1 and 2 analyzed separately) were similar across age and sex groups;
slightly higher values were associated with cycle 2 in the young and old. This
finding contrasts with the original data, which indicated that cycle 2 values
were lower for all age groups. CONCLUSION: The shifts in 25(OH)D distribution
brought about by standardization indicate its importance in drawing correct
conclusions about potential population deficiencies and insufficiencies and in
permitting the comparison of distributions between national surveys.
PMID- 26423387
TI - Gender perceptions predict sex differences in growth patterns of indigenous
Guatemalan infants and young children.
AB - BACKGROUND: Nearly one-half of Guatemalan children experience growth faltering,
more so in indigenous than in nonindigenous children. OBJECTIVES: On the basis of
ethnographic interviews in Totonicapan, Guatemala, which revealed differences in
maternal perceptions about food needs in infant girls and boys, we predicted a
cumulative sex difference in favor of girls that occurred at ~6 mo of age and
diminished markedly thereafter. We examined whether the predicted differences in
age-sex patterns were observed in the village, replicated the examination
nationally for indigenous children, and examined whether the pattern in
nonindigenous children was different. DESIGN: Ethnographic interviews (n = 24) in
an indigenous village were conducted. Anthropometric measurements of the village
children aged 0-35 mo (n = 119) were obtained. National-level growth patterns
were analyzed for indigenous (n = 969) and nonindigenous (n = 1374) children aged
0-35 mo with the use of Demographic and Health Survey (DHS) data. RESULTS:
Mothers reported that, compared with female infants, male infants were hungrier,
were not as satisfied with breastfeeding alone, and required earlier
complementary feeding. An anthropometric analysis confirmed the prediction of
healthier growth in indigenous girls than in indigenous boys throughout the first
year of life, which resulted in a 2.98-cm height-for-age difference (HAD) between
sexes in the village and a 1.61-cm HAD (P < 0.001) in the DHS data between 6 and
17 mo of age in favor of girls. In both data sets, the growth sex differences
diminished in the second year of life (P < 0.05). No such pattern was seen in
nonindigenous children. CONCLUSIONS: We propose that the differences in the HAD
that first favor girls and then favor boys in the indigenous growth patterns are
due to feeding patterns on the basis of gendered cultural perceptions.
Circumstances that result in differential sex growth patterns need to be
elucidated, in particular the favorable growth in girls in the first year of
life.
PMID- 26423386
TI - Postdiagnostic intake of one-carbon nutrients and alcohol in relation to
colorectal cancer survival.
AB - BACKGROUND: Observational data have suggested that intakes of nutrients involved
in one-carbon metabolism are inversely associated with risk of colorectal
carcinoma and adenomas. In contrast, results from some preclinical studies and
cardiovascular and chemoprevention trials have raised concerns that high folate
intake may promote carcinogenesis by facilitating the progression of established
neoplasia. OBJECTIVE: We tested the hypothesis that higher total folate intake
(including food folate and folic acid from fortified foods and supplements) or
other one-carbon nutrient intakes might be associated with poorer survival after
a diagnosis of colorectal cancer. DESIGN: We used rectal and colon cancer cases
within the following 2 US prospective cohort studies: the Nurses' Health Study
and the Health Professionals Follow-Up Study. Biennial questionnaires were used
to gather information on medical history and lifestyle factors, including smoking
and alcohol consumption. B-vitamin and methionine intakes were derived from food
frequency questionnaires. Data on tumor molecular characteristics (including
microsatellite instability, CpG island methylator phenotype, KRAS, BRAF, and
PIK3CA mutations, and long interspersed nucleotide element 1 methylation level)
were available for a subset of cases. We assessed colorectal cancer-specific
mortality according to postdiagnostic intakes of one-carbon nutrients with the
use of multivariable Cox proportional hazards regression models. RESULTS: In 1550
stage I-III colorectal cancer cases with a median follow-up of 14.9 y, we
documented 641 deaths including 176 colorectal cancer-specific deaths. No
statistically significant associations were observed between postdiagnostic
intakes of folate or other one-carbon nutrients and colorectal cancer-specific
mortality (multivariate P-trend >= 0.21). In an exploratory molecular pathologic
epidemiology survival analysis, there was no significant interaction between one
carbon nutrients or alcohol and any of the tumor molecular biomarkers examined.
CONCLUSIONS: Higher postdiagnostic intakes of one-carbon nutrients are not
associated with the prognosis in stage I-III colorectal cancer. Our findings do
not support the hypothesis that higher folate intake after colorectal cancer
diagnosis might increase risk of cancer-related death.
PMID- 26423388
TI - Associations of gestational glycemia and prepregnancy adiposity with offspring
growth and adiposity in an Asian population.
AB - BACKGROUND: Maternal obesity and hyperglycemia increase risk of obesity and
diabetes in offspring later in life. OBJECTIVE: We examined the relation between
gestational glycemia and prepregnancy body mass index (ppBMI) with offspring
growth in an Asian mother-offspring cohort. DESIGN: Pregnant mothers undertook a
75-g 2-h oral-glucose-tolerance test at 26-28 wk of gestation. In 937 singleton
offspring, <=9 serial measurements of weight and length were obtained from birth
until 36 mo of age. RESULTS: Gestational fasting plasma glucose (FPG) was
positively associated with birth weight (B: 0.17; 95% CI: 0.10, 0.24; P < 0.001)
and birth BMI (B: 0.15; 95% CI: 0.06, 0.40; P = 0.001) but not at >=3 mo of age.
In contrast, maternal ppBMI was positively associated with birth variables and
conditional growth in weight and BMI in the first 36 mo of life. However,
gestational FPG and prepregnancy obesity status interacted significantly for the
association with offspring growth and overweight status in the first 36 mo of
life (P-interaction < 0.01). In nonobese mothers, each unit increase in
gestational FPG was associated with increased offspring weight (B: 0.08; 95% CI:
0.008, 0.16; P = 0.03) and BMI (B: 0.08; 95% CI: 0.003, 0.15; P = 0.04) as well
as increased risk of overweight in the first 36 mo of life (OR: 1.36; 95% CI:
1.10, 1.68). However, in obese mothers, each unit increase in gestational FPG was
associated with decreased offspring weight (B: -0.01; 95% CI: -0.02, -0.003) and
BMI (B: -0.008; 95% CI: -0.01, -0.002) velocity (P < 0.01 for both) and decreased
risk of overweight (OR: 0.59; 95% CI: 0.41, 0.86) in the first 36 mo of life.
CONCLUSIONS: Prepregnancy adiposity was associated with offspring growth in early
childhood. Although pooled analyses showed no demonstrable difference by 3 mo of
age, there were contrasting and opposite associations of gestational glycemia
with weight and BMI in the first 36 mo of life in offspring of nonobese and obese
mothers separately. This study was registered at clinicaltrials.gov as
NCT01174875.
PMID- 26423389
TI - Time course of postprandial hepatic phosphorus metabolites in lean, obese, and
type 2 diabetes patients.
AB - BACKGROUND: Impaired energy metabolism is a possible mechanism that contributes
to insulin resistance and ectopic fat storage. OBJECTIVE: We examined whether
meal ingestion differently affects hepatic phosphorus metabolites in insulin
sensitive and insulin-resistant humans. DESIGN: Young, lean, insulin-sensitive
humans (CONs) [mean +/- SD body mass index (BMI; in kg/m(2)): 23.2 +/- 1.5];
insulin-resistant, glucose-tolerant, obese humans (OBEs) (BMI: 34.3 +/- 1.7); and
type 2 diabetes patients (T2Ds) (BMI: 32.0 +/- 2.4) were studied (n = 10/group).
T2Ds (61 +/- 7 y old) were older (P < 0.001) than were OBEs (31 +/- 7 y old) and
CONs (28 +/- 3 y old). We quantified hepatic gammaATP, inorganic phosphate (Pi),
and the fat content [hepatocellular lipids (HCLs)] with the use of (31)P/(1)H
magnetic resonance spectroscopy before and at 160 and 240 min after a high
caloric mixed meal. In a subset of volunteers, we measured the skeletal muscle
oxidative capacity with the use of high-resolution respirometry. Whole-body
insulin sensitivity (M value) was assessed with the use of hyperinsulinemic
euglycemic clamps. RESULTS: OBEs and T2Ds were similarly insulin resistant (M
value: 3.5 +/- 1.4 and 1.9 +/- 2.5 mg . kg(-1) . min(-1), respectively; P = 0.9)
and had 12-fold (P = 0.01) and 17-fold (P = 0.002) higher HCLs, respectively,
than those of lean persons. Despite comparable fasting hepatic gammaATP
concentrations, the maximum postprandial increase of gammaATP was 6-fold higher
in OBEs (0.7 +/- 0.2 mmol/L; P = 0.03) but only tended to be higher in T2Ds (0.6
+/- 0.2 mmol/L; P = 0.09) than in CONs (0.1 +/- 0.1 mmol/L). However, in the
fasted state, muscle complex I activity was 53% lower (P = 0.01) in T2Ds but not
in OBEs (P = 0.15) than in CONs. CONCLUSIONS: Young, obese, nondiabetic humans
exhibit augmented postprandial hepatic energy metabolism, whereas elderly T2Ds
have impaired fasting muscle energy metabolism. These findings support the
concept of a differential and tissue-specific regulation of energy metabolism,
which can occur independently of insulin resistance. This trial was registered at
clinicaltrials.gov as NCT01229059.
PMID- 26423390
TI - Alcohol consumption and risk of cutaneous basal cell carcinoma in women and men:
3 prospective cohort studies.
AB - BACKGROUND: Alcohol consumption has been associated with an increased prevalence
of sunburn, which is an established skin cancer risk factor. OBJECTIVE: We
investigated whether alcohol consumption is associated with risk of cutaneous
basal cell carcinoma (BCC). DESIGN: We conducted a prospective analysis on
alcohol consumption and risk of BCC on the basis of data from 167,765 women in
the NHS (Nurses' Health Study) (1984-2010) and NHS II (1991-2011) and 43,697 men
in the Health Professionals Follow-Up Study (1986-2010). Alcohol intake was
repeatedly assessed every 2-4 y over the follow-up period. HRs and 95% CIs for
BCC in association with alcohol intake were computed with the use of Cox
proportional hazards models with adjustment for sun exposure and other skin
cancer risk factors. RESULTS: A total of 28,951 incident BCC cases were
documented over 3.74 million person-years of follow-up. Increased alcohol intake
was associated with increased BCC risk in both women and men (both P-trend <
0.0001). Pooled multivariable-adjusted HRs over increasing cumulative averaged
alcohol intake categories were 1.00 (reference) for nondrinkers, 1.13 (95% CI:
1.06, 1.20) for 0.1-9.9 g/d, 1.24 (95% CI: 1.14, 1.35) for 10.0-19.9 g/d, 1.27
(95% CI: 1.20, 1.35) for 20.0-29.9 g/d, and 1.22 (95% CI: 1.15, 1.30) for >=30.0
g/d (P-trend < 0.0001, P-heterogeneity by study = 0.10 ). The association
remained consistent when we used alcohol intakes over different latency periods
(0-4, 4-8, 8-12, and 12-16 y) as exposures and over categories of sun exposure
related factors. In the individual alcoholic beverages, white wine and liquor
were positively associated with BCC risk. CONCLUSION: Alcohol consumption is
associated with increased risk of cutaneous BCC in both women and men.
PMID- 26423391
TI - Real-time toxicity and metabolic activity tracking of human cells exposed to
Escherichia coli O157:H7 in a mixed consortia.
AB - Escherichia coli O157:H7 is a significant human pathogen that is continually
responsible for sickness, and even death, on a worldwide scale. While the
pathology of E. coli O157:H7 infection has been well studied, the effect of it's
multiple resulting cytotoxic mechanisms on host metabolic activity has not been
well characterized. To develop a more thorough understanding of these effects,
several bioluminescence assays were evaluated for their ability to track both
toxicity and host metabolic activity levels in real-time. The use of continuously
autobioluminescent human cells was determined to be the most favorable method for
tracking these metrics, as its self-sufficient autobioluminescent phenotype was
unaffected by the presence of the infecting bacteria and its signal could be
measured without cellular destruction. Using this approach, it was determined
that infection with as few as 10 CFU of E. coli O157:H7 could elicit cytotoxic
effects. Regardless of the initial infective dose, an impact on metabolic
expression was not observed until bacterial populations reached levels between 5
* 10(5) and 1 * 10(6) (R(2) = 0.933), indicating that a critical bacterial
infection level must be reached prior to the onset of cytotoxic effects.
Supporting this hypothesis, it was found that cells displaying infection-mediated
metabolic activity reductions could recover to wild type metabolic activity
levels if the infecting bacteria were removed prior to cell death. These results
indicate that rapid treatment of E. coli O157:H7 infection could serve to limit
host metabolic impact and reduce overall host cell death.
PMID- 26423393
TI - Towards multi-level biomonitoring of nematodes to assess risk of nitrogen and
phosphorus pollution in Jinchuan Wetland of Northeast China.
AB - Cultivation for agricultural production often poses threats to nearby wetlands
ecosystems in fertile landscapes. In this study, nematode ecological indexes were
assessed through the main soil properties of the wetlands, farmlands, and edges
of wetlands and farmlands in Jinchuan Wetland by the random sampling. Behavior
and reproduction in Caenorhabditis elegans (C. elegans) exposed to the sampled
waters were also examined. Stress proteins Hsp70 and Hsp90 were measured both in
the living field samples of C. elegans and the lab-tested C. elegans. Our results
suggested that disturbance to wetland ecosystems by nitrogen and phosphorus
reduced nematode richness and proportions of bacterivore nematodes. Bacterivore
nematode diversity and plant-parasitic ecological index were proven to be
sensitive indicators of the ecological health of wetlands. Nematode Hsp70 were
useful biosensors to monitor and assess the levels of nitrogen and phosphorus
pollutions in wetlands. Furthermore, multi-level soil faunal assessments by
canonical correspondence analysis showed that Jinchuan Wetland is threatened with
non-point source pollution from nearby farmlands.
PMID- 26423392
TI - Toxicological challenges to microbial bioethanol production and strategies for
improved tolerance.
AB - Bioethanol production output has increased steadily over the last two decades and
is now beginning to become competitive with traditional liquid transportation
fuels due to advances in engineering, the identification of new production host
organisms, and the development of novel biodesign strategies. A significant
portion of these efforts has been dedicated to mitigating the toxicological
challenges encountered across the bioethanol production process. From the release
of potentially cytotoxic or inhibitory compounds from input feedstocks, through
the metabolic co-synthesis of ethanol and potentially detrimental byproducts, and
to the potential cytotoxicity of ethanol itself, each stage of bioethanol
production requires the application of genetic or engineering controls that
ensure the host organisms remain healthy and productive to meet the necessary
economies required for large scale production. In addition, as production levels
continue to increase, there is an escalating focus on the detoxification of the
resulting waste streams to minimize their environmental impact. This review will
present the major toxicological challenges encountered throughout each stage of
the bioethanol production process and the commonly employed strategies for
reducing or eliminating potential toxic effects.
PMID- 26423394
TI - Acclimation of Hydrilla verticillata to sediment anoxia in vegetation restoration
in eutrophic waters.
AB - Sediment anoxia generally results from intense organic enrichment and is a
limiting factor in the restoration of vegetation in eutrophic waters. To
investigate the effect of sediment anoxia on a typical pollution-tolerant
submerged macrophyte species, Hydrilla verticillata, and acclimation mechanisms
in the plant, a gradient of sediment anoxia was simulated with additions of
sucrose to the sediment, which can stimulate increased concentrations of total
nitrogen, NH4(+) and Fe in pore water. H. verticillata growth was significantly
affected by highly anoxic conditions, as indicated by reduced total biomass in
the 0.5 and 1% sucrose treatments. However, slight anoxia (0.1% sucrose addition)
promoted growth, and the shoot biomass was 22.64% higher than in the control. In
addition to morphologic alterations, H. verticillata showed physiological
acclimations to anoxia, including increased anaerobic respiration and changes in
carbon and nitrogen metabolism in roots. The soluble protein and soluble
carbohydrate contents in roots of the 1% treatment were both significantly higher
compared with those in the control. The increase in alcohol dehydrogenase
activity and pyruvate content in the roots suggested that H. verticillata has a
well-developed capacity for anaerobic fermentation. This study suggests that
highly anoxic sediments inhibit the growth of H. verticillata and the species has
a degree of tolerance to anoxic conditions. Further in situ investigations should
be conducted on the interactions between sediment conditions and macrophytes to
comprehensively evaluate the roles of sediment in the restoration of vegetation
in eutrophic waters.
PMID- 26423395
TI - Metagenomic insights into tetracycline effects on microbial community and
antibiotic resistance of mouse gut.
AB - Antibiotics have been widely used for disease prevention and treatment of the
human and animals, and for growth promotion in animal husbandry. Antibiotics can
disturb the intestinal microbial community, which play a fundamental role in
animals' health. Misuse or overuse of antibiotics can result in increase and
spread of microbial antibiotic resistance, threatening human health and
ecological safety. In this study, we used Illumina Hiseq sequencing, (1)H nuclear
magnetic resonance spectroscopy and metagenomics approaches to investigate
intestinal microbial community shift and antibiotic resistance alteration of the
mice drinking the water containing tetracycline hydrochloride (TET). Two-week TET
administration caused reduction of gut microbial diversity (from 194 to 89
genera), increase in Firmicutes abundance (from 24.9 to 39.8%) and decrease in
Bacteroidetes abundance (from 69.8 to 51.2%). Metagenomic analysis showed that
TET treatment affected the intestinal microbial functions of carbohydrate,
ribosomal, cell wall/membrane/envelope and signal transduction, which is
evidenced by the alteration in the metabolites of mouse serum. Meanwhile, in the
mouse intestinal microbiota, TET treatment enhanced the abundance of antibiotic
resistance genes (ARGs) (from 307.3 to 1492.7 ppm), plasmids (from 425.4 to
3235.1 ppm) and integrons (from 0.8 to 179.6 ppm) in mouse gut. Our results
indicated that TET administration can disturb gut microbial community and
physiological metabolism of mice, and increase the opportunity of ARGs and mobile
genetic elements entering into the environment with feces discharge.
PMID- 26423396
TI - Workload, time and costs of the informal cares in patients with tele-monitoring
of pacemakers: the PONIENTE study.
AB - OBJECTIVES: The purpose of this study was to assess the burden borne by and the
costs to informal caregivers of patients with remotely monitored (RM) pacemakers.
METHODS: The PONIENTE study was a controlled, non-randomised clinical trial, with
data collected from informal caregivers, 12 months after implantation of
pacemakers. The survey on disabilities, personal autonomy, and dependency
situations was used to gather information on demographic and social
characteristics, levels of professionalism, time and types of care, difficulties
in providing care, health status, professional aspects, economic and family or
leisure impacts due to informal caregiving for patients with pacemakers. RESULTS:
During 14 months, 76 caregivers were enrolled in the PONIENTE trial. Of which, 26
were included in the RM group and 50 in the hospital-monitored group (HM). The
mean ages were 58.62 +/- 16.51 and 61.10 +/- 12.67 years, respectively (p = 0.56)
in the groups, and 69.7 % were females. The majority (96.1 %) of the caregivers
declared that they had to provide their services between 6 and 7 days per week
(88.5 % in RM group versus 100 % in HM group; p = 0.037). The costs related to
care provided by the informal caregivers were 21.38 % lower in the RM group than
in the HM group (p = 0.033). CONCLUSIONS: The PONIENTE study shows a significant
impact of informal care on relatives and friends of patients with pacemakers in
terms of their well-being and costs. TRIAL REGISTRATION: ClinicalTrials.gov
NCT02234245.
PMID- 26423398
TI - Analysis of the usage of continence pads and help-seeking behavior of women with
stress urinary incontinence in Poland.
AB - BACKGROUND: Urinary incontinence (UI) in women is a chronic disorder which has a
negative impact on health-related quality of life. Only 45 % of the affected
individuals report the problem with continence to their doctor. The aim of the
study was to assess the duration of stress urinary incontinence (SUI), time from
disease onset to the first medical consultation and in-depth diagnosis, as well
as the need for using continence pads in various grades of SUI. METHODS: We
conducted a cross-sectional study in women who presented at the urogynecologic
ambulatory center and reported urinary incontinence. A total of 420 subjects were
interviewed and underwent urogynecologic and urodynamic examinations. A group of
147 patients with urodynamic SUI was enrolled in the study. RESULTS: All women
were graded according to the Stamey severity score: grade 1 - 56 (38.1 %), grade
2 - 68 (46.3 %), and grade 3 - 23 (15.6 %). Mean time elapsed between disease
onset and presentation at the urogynecologic ambulatory center was 17.4 +/- 11.8
years (grades 1, 2 and 3 for 11.6 +/- 11.8, 14.9 +/- 10.8, and 22.2 +/- 12.1
years, respectively; p = 0.0002). Patients with SUI started perceiving their
condition as a problem 4.7 +/- 5.4 years before referral to urodynamics; 58.3 %
of the SUI patients reported their problems with continence to a physician.
Average time between the onset of UI symptoms and seeking medical help was 13.28
+/- 12.3 years. Mean duration of using continence pads during the day was 4.2,
5.4 and 10.2 years in grades 1, 2 and 3, respectively (p = 0.0002). The number of
patients using continence pads in and outside the home, as compared to outside
only, was: grade 1 - 44.6 % vs. 28.6 %, grade 2 - 77.6 % vs. 13.4 %, and grade 3
86.4 % vs. 9.1 % (p = 0.004). Mean use of continence pads at night was 3.3, 6.1,
and 9.1 years in grades 1, 2 and 3, respectively. The differences were not
statistically significant. Protective continence products were used at night by
26.7 % of the SUI patients: 16.1 %, 25 % and 59.1 % in grades 1, 2 and 3,
respectively (p = 0.004). CONCLUSIONS: Women with SUI delay seeking medical help
for over a decade. The severity of SUI is associated with duration and increased
use of continence pads.
PMID- 26423397
TI - [Management of complications in endoscopic interventions of the upper
gastrointestinal tract].
AB - Endoscopic procedures are frequently performed interventions in the clinical
routine. Whereas endoscopy was initially regarded as being a secondary diagnostic
tool, over the last decades endoscopic procedures have now become an integral
part of various treatment strategies. The appeal of these methods is without any
doubt the minimally invasive approach in contrast to open surgery. Endoscopic
interventions per se necessitate representative technical equipment and the
various components are continually being refined. Considering the complexity of
the method, profound skills in endoscopic diagnostic procedures and therapeutic
interventions are essential prerequisites for adequate procedural quality and
patient safety. Endoscopic examinations are in fact invasive interventions in the
same way as surgical procedures and are associated with a certain risk of
potential complications. The awareness about potential complications and their
respective risk factors is of crucial importance for both the patient and the
physician. Complications may harm patients and may lead to increased mortality
rates; therefore, it is not only important to be aware of them but also to have
an efficient management strategy in order to minimize the damage. Recognition and
consistent actions are the basic pillars of correct complication management.
These aspects are addressed in this article.
PMID- 26423399
TI - Repression of PES1 expression inhibits growth of gastric cancer.
AB - Gastric cancer is one of the leading causes of cancer death worldwide. However,
precise molecular mechanisms underlining its development are far from clear. We
recently reported that PES1 promoted development of breast cancer and ovarian
cancer as an oncogene. In this study, we reported that ablation of endogenous
PES1 resulted in significant suppression of cell proliferation and growth and led
to cell cycle arrest in G2 or G1 phase, respectively, in two gastric cancer cell
lines (AGS and N87) in vitro. Meanwhile, silencing of PES1 obviously decreased
expressions of cyclin D1, HIF-1alpha, and vascular endothelial growth factor
(VEGF) expressions and increased p21WAF1 expression. Re-expression of PES1 in
these two kinds of PES1 knockdown cells rescued these effects. In vivo,
repression of endogenous PES1 expression suppressed gastric tumor growth in nude
mice. In addition, 40.7 % (24/59) of gastric cancer tissues showed PES1
expression via immunohistochemical (IHC) staining. However, there were not any
positive PES1 stainings in matched adjacent tissues. Our results demonstrated
that repression of PES1 changed expressions of some cell proliferation- and
angiogenesis-related genes and inhibited gastric cancer growth, and PES1
expression increased in gastric cancer tissues. These results suggest that PES1
may play an important role in development of gastric cancer. PES1 may be a
potential target for gastric cancer therapy.
PMID- 26423400
TI - ZNRF3 contributes to the growth of lung carcinoma via inhibiting Wnt/beta-catenin
pathway and is regulated by miR-93.
AB - Lung carcinoma is the most common cancer with increasing morbidity, inefficient
therapeutic modality, and poor prognosis, due to the lack of understanding of its
related molecular mechanism. ZNRF3 is a newly identified negative regulator of
Wnt signaling. In this study, we found that ZNRF3 level is reduced in lung
carcinoma compared with normal lung tissue and its expression level is positively
correlated with the survival of lung cancer patients. Restoration of ZNRF3
suppressed the proliferation and cell cycle progression of lung cancer cell
lines. Suppression of ZNRF3 expression in normal lung cells increased the
proliferation rates. In an animal model, ZNRF3 was shown to suppress the growth
of lung cancer xenografts. ZNRF3 was shown to negatively regulate the activation
of Wnt signaling in lung cancerous and normal cells. Further studies revealed
that ZNRF3 is a target of miR-93, an oncogenic microRNA (miRNA) for lung cancer
progression. Collectively, we found that miR-93/ZNRF3/Wnt/beta-catenin regulatory
network contributes to the growth of lung carcinoma. Targeting this pathway may
be a promising strategy for lung cancer therapy.
PMID- 26423401
TI - PMS2 expression in epithelial ovarian cancer is posttranslationally regulated by
Akt and essential for platinum-induced apoptosis.
AB - Epithelial ovarian cancer (EOC) is the most lethal of the gynecologic
malignancies, mainly due to the advanced stage at diagnosis and development of
cisplatin resistance. The sensitivity of tumor cells to cisplatin is frequently
affected by defect in DNA mismatch repair (MMR), which repairs mispaired DNA
sequences and regulates DNA-damage-induced apoptosis. However, the role of
postmeiotic segregation increased 2 (PMS2), a member of MMR protein family, in
cisplatin resistance remains elusive. In the present study, we demonstrated the
frequent deficiency of PMS2 and phosphorylation of Akt in EOC cell lines and
tissues. Results of complex immunoprecipitation (co-IP) and protein stability
assay indicated that activated Akt could directly bind to PMS2 and cause
degradation of PMS2 in EOC cells. In addition, functional experiments revealed
that PMS2 was required for cisplatin-induced apoptosis and cell cycle arrest in
G2/M phase. These findings provide a novel insight into molecular mechanisms
linking MMR with chemoresistance and suggest that stabilization of PMS2
expression may be useful in overcoming the cisplatin resistance in EOC.
PMID- 26423402
TI - Harnessing the immunomodulatory effect of thermal and non-thermal ablative
therapies for cancer treatment.
AB - Minimally invasive interventional therapies are evolving rapidly and their use
for the treatment of solid tumours is becoming more extensive. The in situ
destruction of solid tumours by such therapies is thought to release antigens
that can prime an antitumour immune response. In this review, we offer an
overview of the current evidence for immune response activation associated with
the utilisation of the main thermal and non-thermal ablation therapies currently
in use today. This is followed by an assessment of the hypothesised mechanisms
behind this immune response priming and by a discussion of potential methods of
harnessing this specific response, which may subsequently be applicable in the
treatment of cancer patients. References were identified through searches of
PubMed/MEDLINE and Cochrane databases to identify peer-reviewed original
articles, meta-analyses and reviews. Papers were searched from 1850 until October
2014. Articles were also identified through searches of the authors' files. Only
papers published in English were reviewed. Thermal and non-thermal therapies have
the potential to stimulate antitumour immunity although the current body of
evidence is based mostly on murine trials or small-scale phase 1 human trials.
The evidence for this immune-modulatory response is currently the strongest in
relation to cryotherapy and radiotherapy, although data is accumulating for
related ablative treatments such as high-intensity focused ultrasound,
radiofrequency ablation and irreversible electroporation. This effect may be
greatly enhanced by combining these therapies with other immunostimulatory
interventions. Evidence is emerging into the immunomodulatory effect associated
with thermal and non-thermal ablative therapies used in cancer treatment in
addition to the mechanism behind this effect and how it may be harnessed for
therapeutic use. A potential exists for treatment approaches that combine
ablation of the primary tumour with control and possible eradication of
persistent, locally recurrent and metastatic disease. However, more work is
needed into each of these modalities, initially in further animal studies and
then subsequently in large-scale prospective human studies.
PMID- 26423404
TI - The clinical significance of systemic inflammation score in esophageal squamous
cell carcinoma.
AB - The objective of this study was to investigate the clinical significance of
systemic inflammation score (SIS) and prognostic nutritional index (PNI) in
esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy.
Records from 206 patients with histologically diagnosed ESCC who underwent
esophagectomy at Qilu Hospital of Shandong University from January 2007 to
December 2008 were retrospectively reviewed. The median disease-free survival
(DFS) of this cohort was 32.3 months and 5-year DFS was 34.5 %. The median
overall survival (OS) was 39.5 months and 5-year OS was 40.8 %. We found that
high SIS was significantly associated with increased tumor length (p = 0.021),
increased depth of invasion (p = 0.001), lymph node metastasis (p = 0.038), and
advanced pathological stage (p = 0.004). Kaplan-Meier survival analysis revealed
that both high SIS and low PNI were significantly associated with inferior DFS
(for the SIS, p = 0.005; for the PNI, p = 0.003) and OS (for the SIS, p = 0.007;
for the PNI, p = 0.002). In multivariate analysis, SIS was an independent
prognostic indicator for both DFS and OS. However, PNI was not an independent
prognosticator in multivariate analysis. SIS was a novel and promising
inflammation-based prognostic score than PNI in ESCC patients who underwent
esophagectomy.
PMID- 26423405
TI - Tissue expression levels of miR-29b and miR-422a in children, adolescents, and
young adults' age groups and their association with prediction of poor prognosis
in human osteosarcoma.
AB - Osteosarcoma is the most common type of bone cancer in children and adolescents.
MicroRNAs (miRNAs) play important roles in the development, differentiation, and
function of different cell types and in the pathogenesis of various human
diseases. miRNAs are differentially expressed in normal and cancer cells. The
investigation of miRNA expression between healthy subjects and patients with
osteosarcoma is crucial for future clinical trials. In this study, the expression
levels of miRNAs were detected by qRT-PCR. Correlation between expression levels
of tow miRNAs and different clinicopathological characteristics were analyzed
using the chi (2) test. Survival rate was detected using the log-rank test and
Kaplan-Meier method. qRT-PCR was shown that expression levels of miR-29b and miR
422a were strongly decreased in osteosarcoma bone tissue compared with
noncancerous bone tissues. Our result indicated that the low expression levels of
miR-29b and miR-422a showed strong correlation with large tumor size (P = 0.20;
0.029), advanced TNM stage (P = 0.001; 0.012), distant metastasis (P = 0.008;
0.019), and grade of tumor (P = 0.009; 0.016). Kaplan-Meier survival analysis
showed that the low expressions of miR-29b/miR-422a were correlated with shorter
time overall survival (log-rank test, P = 0.009; P = 0.013). Moreover,
multivariate Cox proportional hazards model indicated that miR-29b and miR-422a
(P = 0.024; P = 0.016) were independent prognostic markers of overall survival of
patients. Our result indicated that downregulation of miR-29b and miR-422a may be
linked to the prediction of poor prognosis, indicating that miR-29b and miR-422a
may be a valuable prognostic marker for osteosarcoma patients.
PMID- 26423403
TI - The potential role of the NEK6, AURKA, AURKB, and PAK1 genes in adenomatous
colorectal polyps and colorectal adenocarcinoma.
AB - Colorectal adenomatous polyp (CRAP) is a major risk factor for the development of
sporadic colorectal cancer (CRC). Histone modifications are one of the epigenetic
mechanisms that may have key roles in the carcinogenesis of CRC. The objective of
the present study is to investigate the alternations in the defined histone
modification gene expression profiles in patients with CRAP and CRC. Histone
modification enzyme key gene expressions of the CRC, CRAP, and control groups
were evaluated and compared using the reverse transcription PCR (RT-PCR) array
method. Gene expression analysis was performed in the CRAP group after dividing
the patients into subgroups according to the polyp diameter, pathological
results, and morphological parameters which are risk factors for developing CRC
in patients with CRAP. PAK1, NEK6, AURKA, AURKB, HDAC1, and HDAC7 were
significantly more overexpressed in CRC subjects compared to the controls (p <
0.05). PAK1, NEK6, AURKA, AURKB, and HDAC1 were significantly more overexpressed
in the CRAP group compared to the controls (p < 0.005). There were no significant
differences between the CRAP and CRC groups with regards to PAK1, NEK6, AURKA, or
AURKB gene overexpression. PAK1, NEK6, AURKA, and AURKB were significantly in
correlation with the polyp diameter as they were more overexpressed in polyps
with larger diameters. In conclusion, overexpressions of NEK6, AURKA, AURKB, and
PAK1 genes can be used as predictive markers to decide the colonoscopic
surveillance intervals after the polypectomy procedure especially in polyps with
larger diameters.
PMID- 26423406
TI - Denosumab increases sublesional bone mass in osteoporotic individuals with recent
spinal cord injury.
AB - Osteoporosis is a frequent complication related to spinal cord injury (SCI), and
data on osteoporosis treatment after SCI is scarce. Treatment with denosumab
increases lumbar and femoral BMD and decreases bone turnover markers in
individuals with recent SCI. This drug may be a promising therapeutic option in
SCI-related osteoporosis. INTRODUCTION: Osteoporosis development is a frequent
complication related to SCI, especially at the sublesional level. Nevertheless,
data on osteoporosis treatment after SCI is scarce, particularly short term after
injury, when the highest bone loss is produced. The aim of this study was to
analyze the efficacy of denosumab in the treatment of SCI-related osteoporosis.
METHODS: Fourteen individuals aged 39 +/- 15 years with osteoporosis secondary to
recent SCI (mean injury duration 15 +/- 4 months) were treated with denosumab for
12 months. Bone turnover markers (BTMs) (PINP, bone ALP, sCTx), 25-hydroxyvitamin
D (25OHD) levels and bone mineral density (BMD) at the lumbar spine (LS), total
hip (TH), and femoral neck (FN) were assessed at baseline and at 12 months. All
participants received calcium and vitamin D supplementation. RESULTS: At 12
months, SCI denosumab-treated participants showed a significant increase in BMD
at TH (+2.4 +/- 3.6 %, p = 0.042), FN (+3 +/- 3.6 %, p = 0.006), and LS (+7.8 +/-
3.7 %, p < 0.001) compared to baseline values. Denosumab treatment was associated
with significant decreases in BTMs (bone ALP -42 %, p < 0.001; PINP -58 %, p <
0.001, sCTx -57 %, p = 0.002) at 12 months. BMD evolution was not related to BTM
changes or 25OHD serum levels. No skeletal fractures or serious adverse events
were observed during follow-up. CONCLUSIONS: Treatment with denosumab increases
lumbar and femoral BMD and decreases bone turnover markers in individuals with
recent SCI. This drug may be a promising therapeutic option in SCI-related
osteoporosis.
PMID- 26423408
TI - Deep shaving and transanal disc excision in large endometriosis of mid and lower
rectum: the Rouen technique.
AB - BACKGROUND: Colorectal resection is performed in a majority of patients
presenting with large endometriosis of mid and lower rectum; however, it may
negatively and irreversibly impact postoperative rectal function. To avoid such
unfavourable outcomes, we propose an original technique combining laparoscopic
deep rectal shaving and transanal disc excision using a semi-circular stapler.
METHODS: The video presents the procedure performed in a 29-year-old nullipara
referred with a large endometriotic nodule infiltrating the lower rectum on more
than 30 mm length. The first step is laparoscopic and involves deep rectal
shaving performed using exclusively the plasma energy. Then, transanal excision
of shaved area is performed, by placing traction parachute sutures in the middle
and outside the shaved area. Their traction induces the prolapse of shaved area
that is resected using a semicircular stapler. Insufflating the rectum with air
checks the integrity of the staple line. RESULTS: Operative time was 210 min.
Immediate postoperative outcomes were uneventful, and bowel movements were normal
beginning with day 6. Our technique is suitable in large rectal nodules located
up to 10 cm above the anus, infiltrating the rectum on up to 6 cm length, and
these parameters are preoperatively assessed using MRI and computed tomography.
To date, it was successfully carried out in 29 women with large deep
endometriosis of the mid and lower rectum. Rectovaginal fistula was recorded in
one patient (3.6 %) and transitory bladder dysfunction in seven patients (25 %).
Digestive function assessment using standardized questionnaires revealed an
overall improvement, without de novo anal continence troubles. Postoperative
pregnancy rate was 78 % with a majority of patients having conceived
spontaneously. CONCLUSIONS: Based on our experience, we believe that our
conservative technique is feasible and reproducible in large mid and lower rectal
endometriosis and might avoid the risk of unfavourable outcomes related to low
colorectal resection.
PMID- 26423407
TI - Risk of Cardiovascular Disease in an Aging HIV Population: Where Are We Now?
AB - With more effective and widespread antiretroviral treatment, the overall
incidence of AIDS- or HIV-related death has decreased dramatically. Consequently,
as patients are aging, cardiovascular disease (CVD) has emerged as an important
cause of morbidity and mortality in the HIV population. The incidence of CVD
overall in HIV is relatively low, but it is approximately 1.5-2-fold higher than
that seen in age-matched HIV-uninfected individuals. Multiple factors are
believed to explain this excess in risk such as overrepresentation of traditional
cardiovascular risk factors (particularly smoking), toxicities associated with
cumulative exposure to some antiretroviral agents, together with persistent
chronic inflammation, and immune activation associated with HIV infection. Tools
are available to calculate an individual's predicted risk of CVD and should be
incorporated in the regular follow-up of HIV-infected patients. Targeted
interventions to reduce this risk must be recommended, including life-style
changes and medical interventions that might include changes in antiretroviral
therapy.
PMID- 26423409
TI - Intraperitoneal onlay mesh reinforcement of the abdominal wall: a new surgical
option for treatment of anterior cutaneous nerve entrapment syndrome-a
retrospective cohort analysis of 30 consecutive patients.
AB - BACKGROUND: The aim of the study was to introduce a new surgical treatment for
anterior cutaneous nerve entrapment syndrome, a frequently unrecognised disorder
in the general population responsible for chronic abdominal wall pain with
limited treatment options to date. We hypothesised that intraperitoneal onlay
mesh reinforcement could dissipate excessive increases in intra-abdominal
pressure and prevent entrapment of the neurovascular bundle. METHODS:
Retrospective cohort analysis was performed between September 2002 and March
2014. All consecutive patients diagnosed with anterior cutaneous nerve entrapment
syndrome refractory to conservative treatment (n = 30) underwent laparoscopic
intraperitoneal onlay mesh reinforcement of the painful area in the abdominal
wall. Planned follow-up took place at 2, 6 and 12 weeks after surgery and at time
of analysis (March 2015). Primary outcome was patients' satisfaction after
treatment at short and long term (last follow-up) using a verbal rating score as
measurement (1 = I am very satisfied; I never experience pain, 2 = I am
satisfied; I occasionally experience some pain, 3 = I have improved but
experience pain on a regular basis, 4 = I have had no result on this treatment, 5
= my pain is worse after treatment). Scores 1 and 2 were classified as success,
and scores 4 and 5 as failure of the treatment. RESULTS: Thirty patients
underwent laparoscopic intraperitoneal onlay mesh reinforcement. None were lost
to follow-up (mean 54 +/- 44 months, range 12-122, median 38). Short- and long
term success rates were 90 and 71 %, respectfully. CONCLUSIONS: Intraperitoneal
onlay mesh reinforcement of the abdominal wall seems to be a promising option for
the treatment of intractable anterior cutaneous nerve entrapment syndrome.
PMID- 26423410
TI - Backflow prevention mechanism of laparoscopic Toupet fundoplication using high
resolution manometry.
AB - BACKGROUND: The use of multichannel intraluminal impedance pH (MII-pH) and high
resolution manometry (HRM), which are new devices used to examine the esophageal
function, has recently become common in Europe and the USA, thus garnering much
attention. There have not been enough studies as of yet, however, on the
esophageal motor function and the benefits of treatment after these devices have
been used in laparoscopic fundoplication. OBJECTIVE: To use MII-pH and HRM to
study the treatment effectiveness of laparoscopic fundoplication and consider a
backflow prevention mechanism for laparoscopic Toupet fundoplication. MATERIALS
AND METHODS: The study looked at 27 of a total of 60 patients undergoing
laparoscopic fundoplication due to reasons of either gastroesophageal reflux
disease or esophageal hiatal hernia between October 2012 and February 2014, who
underwent a postsurgical HRM examination. Of these, 25 patients whose symptoms
disappeared following surgery and who were not orally administered gastric
secretion inhibitor (of whom nine were male, average age 55.9 +/- 14.9 years, and
of whom 76 % underwent MII-pH) were taken as the subjects of the study. The
postsurgical evaluation was conducted 3 months after the operation. RESULTS:
Using HRM, although no change was noted in the lower esophageal sphincter
pressure (LESP) (p = 0.943), an increase in lower esophageal sphincter pressure
integral (p = 0.024) and extensions in both overall length and abdominal length
were noted (both p < 0.001), while a significant improvement was noted in the
lower esophageal sphincter (LES). Furthermore, the cases subjected to MII-pH
demonstrated a reduced gastroesophageal reflux time, total number of liquid
reflux episodes, and total number of reflux episodes (p < 0.001, p = 0.008, p =
0.009). CONCLUSIONS: Backflow prevention mechanism of laparoscopic Toupet
fundoplication is thus considered to improve the overall LES function without
elevating LESP.
PMID- 26423411
TI - A single-centre experience of relaparoscopy in complications of laparoscopic
inguinal hernia repair-feasibility and outcomes.
AB - BACKGROUND: Management of complications of laparoscopic inguinal hernia repair
remains challenging as well as debatable. Relaparoscopy in management of these
complications is relatively newer concept. We tried to analyse the feasibility of
relaparoscopy (transabdominal preperitoneal approach) in management of
complications of laparoscopic inguinal hernia repair. MATERIALS AND METHODS: The
study group included 61 patients (referral cases) from a prospectively maintained
database of previous laparoscopic inguinal hernia surgery with majority of the
patients of recurrence (n = 39). Other complications were mesh infections (n =
15), pubic osteitis (n = 3), migration of mesh into adjacent viscera (n = 3) and
meralgia paresthetica (n = 1). All patients underwent transabdominal
preperitoneal approach (TAPP) between January 2007 and December 2013. RESULTS AND
OUTCOME: Most of the patients had previous TEP repair (n = 49) with variable
complications detected in the range of 9 days to 38 months. Small-sized mesh (n =
12) and rolled up mesh (n = 10) were the causes of recurrence in 57 % cases.
Mycobacterium tuberculosis (40 %) and mixed bacterial infections (33 %) strains
were detected in the infected mesh. Pubic osteitis and meralgia paresthetica were
tackers induced. All patients dealt with TAPP approach. Recurrent hernia cases
underwent mesh placement and infected mesh was removed in mesh infection. Tackers
were removed in cases of osteitis pubis and meralgia paraesthesia. Median
operative time was 62 min (42-126 min) and hospital stay 3 days (2-13 days). The
relaparoscopy was accomplished in 95.1 % of cases with no major intraoperative
complications and minimal postoperative morbidity. CONCLUSION: Relaparoscopy
through TAPP approach remains safe and feasible option to deal with primary
laparoscopic hernia repair complications. Surgical techniques during primary
laparoscopic repair are important cause for aforementioned complications. Though,
surgical expertize remains warranted for relaparoscopy.
PMID- 26423412
TI - Transanal Hartmann reversal: a new technique.
AB - BACKGROUND: Hartmann procedure consists in a sigmoidectomy followed by a terminal
colostomy. However, the stoma is associated with complications and suboptimal
quality of life, so the restoration of colonic continuity should be, at least,
considered in any case. Open restoration has been associated with significant
morbidity and mortality; therefore, many authors have described the advantages of
laparoscopic Hartmann reversal. We want to go a step further showing our
experience using a combined laparoscopic and transanal approach in an attempt to
improve the surgical technique. METHODS: Patients with an end colostomy due to an
emergency Hartmann procedure are selected for this intervention. This approach is
performed simultaneously laparoscopically and transanally, with single-port
devices, through the colostomy wound in the first case and trough anal canal in
the second one. The previous stapler line is resected transanally and the
proximal rectum and mesorectum are dissected until the peritoneal reflexion,
where both teams work together to complete the adhesiolysis. Finally an end-to
end anastomosis is performed under laparoscopic control. RESULTS: As in patients
with rectal cancer, dissection of the stump in Hartmann reversal procedure may be
better and associated with shorter operative time. CONCLUSIONS: As with any new
surgical procedure, it is probably too early to draw conclusions, but nowadays
transanal combined with laparoscopic approach seems to be a safe and feasible
technique to perform a Hartmann reversal.
PMID- 26423414
TI - The use of endoluminal vacuum (E-Vac) therapy in the management of upper
gastrointestinal leaks and perforations.
AB - INTRODUCTION: Upper intestinal leaks and perforations are associated with high
morbidity and mortality rates. Despite the growing experience using
endoscopically placed stents, the treatment of these leaks and perforations
remain a challenge. Endoluminal vacuum (E-Vac) therapy is a novel treatment that
has been successfully used in Germany to treat upper gastrointestinal leaks and
perforations. There currently are no reports on its use in the USA. METHODS: E
Vac therapy was used to treat 11 patients with upper gastrointestinal leaks and
perforations from September 2013 to September 2014. Five patients with leaks
following sleeve gastrectomy were excluded from this study. A total of six
patients were treated with E-Vac therapy; these included: (n = 2) iatrogenic
esophageal perforations, (n = 1) iatrogenic esophageal and gastric perforations,
(n = 1) iatrogenic gastric perforation, (n = 1) gastric staple line leak
following a surgical repair of a traumatic gastric perforation, and (n = 1)
esophageal perforation due to an invasive fungal infection. Four patients had
failed an initial surgical repair prior to starting E-Vac therapy. RESULTS: All
six patients (100 %) had complete closure of their perforation or leak after an
average of 35.8 days of E-Vac therapy requiring 7.2 different E-Vac changes. No
deaths occurred in the 30 days following E-Vac therapy. One patient died
following complete closure of his perforation and transfer to an acute care
facility due to an unrelated complication. There were no complications directly
related to the use of E-Vac therapy. Only one patient had any symptoms of
dysphagia. This patient had severe dysphagia from an esophagogastric anastomotic
stricture prior to her iatrogenic perforations. Following E-Vac therapy, her
dysphagia had actually improved and she could now tolerate a soft diet.
CONCLUSIONS: E-Vac therapy is a promising new method in the treatment of upper
gastrointestinal leaks and perforations. Current successes need to be validated
through future prospective controlled studies.
PMID- 26423413
TI - Outcomes of endoscopic treatment of second recurrences of large nonpedunculated
colorectal adenomas.
AB - BACKGROUND AND AIMS: Piecemeal endoscopic mucosal resection (EMR) of large
nonpedunculated colorectal adenomas is associated with significant recurrence
rates. After salvage endoscopic treatment of recurrences, there is a significant
rate of second recurrences. There is a paucity of data on the efficacy and safety
of continued endoscopic treatment after a second recurrence. METHODS: Consecutive
patients with recurrent adenomas after initial piecemeal EMR of nonpedunculated
colorectal adenomas >2 cm were reviewed. We assessed the feasibility, safety and
efficacy of continued endoscopic treatment in these patients. RESULTS: Sixty-four
patients with 70 recurrent lesions were identified. All were retreated
endoscopically. Follow-up colonoscopy (mean interval 6.4 months) was performed on
62/70 lesions (89 %), and a second recurrence was found in 21/62 (34 %). One
patient underwent surgery for a circumferential adenoma of the ileocecal valve.
The other 20 lesions were treated endoscopically. Follow-up colonoscopy was
performed on 15/20 (75 %) and demonstrated a third recurrence in 3/15 (20 %). One
was a deep T1 cancer; curative surgery was performed. The other two patients each
had one additional endoscopic treatment and both had no recurrence on subsequent
colonoscopy. There were two complications: Both were delayed bleeds after
treatment of the first recurrence. A mean of 1.3 endoscopic procedures was
required to achieve a cure (range 1-3) for recurrent adenomas after piecemeal
EMR. CONCLUSION: Endoscopic treatment of patients with second recurrences is safe
and effective, but is associated with a significant rate of additional
recurrences. Continued endoscopic treatment of patients with multiple recurrences
is associated with high cure rates, low complication rates and a low risk of
progression to malignancy.
PMID- 26423415
TI - Learning curve analysis of colorectal endoscopic submucosal dissection (ESD) for
laterally spreading tumors by endoscopists experienced in gastric ESD.
AB - BACKGROUND: Endoscopic submucosal dissection (ESD) for various colorectal
neoplasms is more technically difficult than gastric ESD. We evaluated treatment
outcomes and the learning curve for colorectal ESD of laterally spreading tumors
(LSTs) based on the experience of a single endoscopist. METHODS: We included 93
colorectal ESD procedures for colorectal LST that were performed between March
2009 and June 2012 by a single experienced endoscopist who previously performed
hundreds of cases of gastric ESD. The cases were grouped chronologically into
three periods by multi-dimensional analyses. For procedure time, the learning
curve was analyzed using the moving average method, and for complication, the
learning curve was analyzed using cumulative sum (cusum) method. RESULTS: The
median procedure time for 93 colorectal ESD was 45 min, and the rates of en bloc
resection and R0 resection were 89.25 and 83.87 %. When results were compared
among three periods in order to determine the learning curve, the procedure time
and en bloc resection rates were not significantly different. However, the
procedure proficiency (about 0.16 cm(2)/min) was significantly faster during the
second period, after about 25 cases of colorectal ESD. In the third period (about
50 cases), the number and rate of en bloc resection (over 90 %) reached the same
as that of en bloc R0 resection. When comparing outcomes based on LST subtype,
the procedure proficiency of LST-granular type (LST-G) was significantly faster
than that of LST-non granular type (LST-NG) (LST-NG, 0.072 cm(2)/min; LST-G,
0.157 cm(2)/min; p = 0.01). CONCLUSION: Endoscopists fully experienced in gastric
ESD need a relatively short learning period for colorectal ESD in terms of
procedure time and complication. However, approximately 50 cases might be needed
to acquire an adequate skill of colorectal ESD for LST in an experienced gastric
ESD endoscopist. Colorectal ESD for LST-NG seems to have higher technical
difficulty and a longer learning curve than LST-G.
PMID- 26423416
TI - Risk factors for under-diagnosis of gastric intraepithelial neoplasia and early
gastric carcinoma in endoscopic forceps biopsy in comparison with endoscopic
submucosal dissection in Chinese patients.
AB - Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and
endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia
(GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The
aim of the study was to investigate risk factors for under-diagnosed pathology in
initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic
findings for tumor location, size, macroscopic pattern, nodularity, erythema,
erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria.
Differences in those features between EFB and ESD were compared and risk factors
for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %)
cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were
upgraded in ESDs. Compared to the concordant group, the lesion size >=2 cm, and
depressed and excavated patterns were significantly more frequent in the upgraded
group. Further multivariate regression analysis demonstrated the depressed
pattern and lesion size >=2 cm as independent risk factors for upgraded pathology
with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535
(95 % confidence interval 1.257-5.111), respectively. Lesion size >=2.0 cm and
the depressed pattern at initial EFB were independent risk factors for pathologic
upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics
should be considered together with the initial EFB diagnosis to guide the optimal
clinical management of patients with GIN and EGC.
PMID- 26423417
TI - Thoracoscopic management of volvulus of the gastric conduit following minimally
invasive Ivor-Lewis esophagectomy.
AB - BACKGROUND: We present a case of emergent thoracoscopic management of volvulus of
the gastric conduit following minimally invasive Ivor-Lewis esophagectomy. The
patient is a 69-year-old Caucasian male with a history of adenocarcinoma of the
lower third of the esophagus. Initial presentation was dysphagia with solid
foods, which progressed in severity until he was unable to swallow anything. EUS
demonstrated a partially obstructing mass at 33 cm; biopsy revealed poorly
differentiated adenocarcinoma, stage T3N2Mx. PET scan did not reveal any
metastatic disease. Preoperative management included neo-adjuvant chemoradiation
therapy (5-FU and cisplatin) and early placement of a jejunal feeding tube. Intra
operative leak test was performed as a matter of routine following completion of
the esophagogastric anastomosis. A nasogastric tube was placed intra-operatively
and removed on POD2 according to our standard pathway. Postoperatively, the
patient progressed without difficulty to POD4, when we routinely obtain an upper
GI swallow study. This demonstrated a lack of transit of contrast through the
distal neo-esophagus. Follow-up endoscopy revealed volvulus of the gastric
conduit with obliteration of the lumen. METHOD: We immediately took the patient
to the OR for thoracoscopic detorsion, which we accomplished successfully by
entering the existing trochar sites and using blunt dissection.?Upon entering the
thoracic cavity, the staple line that had been oriented anteriorly was now
posterior. Attachments were gently teased away from the chest wall and the
conduit was detorsed and anchored to the chest wall in the correct orientation
with silk suture. Intra-operative endoscopy demonstrated a patent conduit.
RESULTS: Postoperative upper GI fluoroscopy now showed good transit of contrast.
The patient continued to improve and was eventually advanced to mechanical soft
diet and discharged on postoperative day 9. CONCLUSIONS: Early intervention is
indicated in cases of volvulus of the gastric conduit following Ivor-Lewis
esophagectomy.
PMID- 26423376
TI - Comparative effectiveness of immediate antiretroviral therapy versus CD4-based
initiation in HIV-positive individuals in high-income countries: observational
cohort study.
AB - BACKGROUND: Recommendations have differed nationally and internationally with
respect to the best time to start antiretroviral therapy (ART). We compared
effectiveness of three strategies for initiation of ART in high-income countries
for HIV-positive individuals who do not have AIDS: immediate initiation,
initiation at a CD4 count less than 500 cells per MUL, and initiation at a CD4
count less than 350 cells per MUL. METHODS: We used data from the HIV-CAUSAL
Collaboration of cohort studies in Europe and the USA. We included 55,826
individuals aged 18 years or older who were diagnosed with HIV-1 infection
between January, 2000, and September, 2013, had not started ART, did not have
AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of
HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining
illness, mean survival time, the proportion of individuals in need of ART, and
the proportion of individuals with HIV-RNA viral load less than 50 copies per mL,
as would have been recorded under each ART initiation strategy after 7 years of
HIV diagnosis. We used the parametric g-formula to adjust for baseline and time
varying confounders. FINDINGS: Median CD4 count at diagnosis of HIV infection was
376 cells per MUL (IQR 222-551). Compared with immediate initiation, the
estimated relative risk of death was 1.02 (95% CI 1.01-1.02) when ART was started
at a CD4 count less than 500 cells per MUL, and 1.06 (1.04-1.08) with initiation
at a CD4 count less than 350 cells per MUL. Corresponding estimates for death or
AIDS-defining illness were 1.06 (1.06-1.07) and 1.20 (1.17-1.23), respectively.
Compared with immediate initiation, the mean survival time at 7 years with a
strategy of initiation at a CD4 count less than 500 cells per MUL was 2 days
shorter (95% CI 1-2) and at a CD4 count less than 350 cells per MUL was 5 days
shorter (4-6). 7 years after diagnosis of HIV, 100%, 98.7% (95% CI 98.6-98.7),
and 92.6% (92.2-92.9) of individuals would have been in need of ART with
immediate initiation, initiation at a CD4 count less than 500 cells per MUL, and
initiation at a CD4 count less than 350 cells per MUL, respectively.
Corresponding proportions of individuals with HIV-RNA viral load less than 50
copies per mL at 7 years were 87.3% (87.3-88.6), 87.4% (87.4-88.6), and 83.8%
(83.6-84.9). INTERPRETATION: The benefits of immediate initiation of ART, such as
prolonged survival and AIDS-free survival and increased virological suppression,
were small in this high-income setting with relatively low CD4 count at HIV
diagnosis. The estimated beneficial effect on AIDS is less than in recently
reported randomised trials. Increasing rates of HIV testing might be as important
as a policy of early initiation of ART. FUNDING: National Institutes of Health.
PMID- 26423418
TI - Minimally invasive approaches to resection of benign/low-grade gastric tumors.
AB - BACKGROUND: Tumors in the stomach have traditionally been treated with either
subtotal gastrectomy or total gastrectomy, depending on the location. However,
many of these lesions are benign spindle cell tumors or adenomas and could be
resected with margins. Here, we explore multiple minimally invasive methods for
the resection of these tumors. We highlight a wedge resection, a circumferential
resection with transverse closure, a transgastric resection, and an
endoscopic/laparoscopic submucosal resection. The wedge resection was performed
in a 71-year-old man found to have a mass in the stomach on screening upper
endoscopy. The biopsy was not definitive, but on CT scan there was a 4.5-cm
submucosal mass consistent with a gastrointestinal stromal tumor. The
circumferential resection was performed for an 83-year-old woman who had
abdominal discomfort which led to an upper endoscopy. She was found to have a
mass in the lesser curve of her stomach. Biopsy revealed this to be a
gastrointestinal stromal tumor. Ultimately, it was removed when serial CT scans
showed that it was growing. The transgastric approach was used for a 75-year-old
man who had upper endoscopy for reflux symptoms and was found to have a mass in
the stomach. Biopsy showed that it was a gastrointestinal stromal tumor. Due to
patient preference, it was initially observed but was eventually removed when it
was found to be growing on serial CT scans. The endoscopic/laparoscopic approach
was for a 65-year-old man who had an upper endoscopy performed for work-up of
melena and was found to have a 5-cm mass at the gastroesophageal junction. The
biopsy showed this to be an adenoma, and he went on to have it removed. METHODS:
We identified representative videos from patients treated with each of the above
techniques. Small exophytic lesions can be completely excised with a wedge
resection using a stapler to fire across the base of the lesion. By contrast, if
the lesion is in an awkward location or is too large to remove in this way, a
vessel-sealing device can divide the mass from the stomach circumferentially
(intragastric resection). The resultant defect in the gastric wall must be
repaired transversely to avoid narrowing the lumen. Endophytic lesions can be
treated with transgastric resection. Ports are placed directly into the stomach
allowing excision from within the stomach. Finally, submucosal resection is ideal
for lesions close to the GE junction. This combined endoscopic and laparoscopic
approach allows the tumor to be lifted off the muscle fibers and to be resected
without transmural injury to the stomach or esophagus. RESULTS: All four patients
tolerated the procedure well and were discharged home by postoperative day 2.
There were no complications. One patient, the one who underwent the
endoscopic/laparoscopic approach and was preoperatively found to have an adenoma
on biopsy, was ultimately found to have an invasive component and later underwent
total gastrectomy. The other three patients all had gastrointestinal stromal
tumors. CONCLUSIONS: Minimally invasive techniques should be considered more
frequently for the management of benign gastric tumors. The four methods
illustrated here can be used safely and result in faster recovery as well as
shorter hospital stays compared to traditional approaches.
PMID- 26423421
TI - A Sociological Perspective.
PMID- 26423420
TI - Peer interviewing in medical education research: experiences and perceptions of
student interviewers and interviewees.
AB - BACKGROUND: Interviewing is one of the main methods used for data collection in
qualitative research. This paper explores the use of semi-structured interviews
that were conducted by students with other students in a research study looking
at cultural diversity in an international medical school. Specifically this paper
documents and gives 'voice' to the opinions and experiences of interviewees and
interviewers (the peers and the communities) on the value of peer interviewing in
the study and outlines (1) the preparation made to address some of the foreseen
challenges, (2) the challenges still faced, and (3) the benefits of using peer
interviews with respect to the research study, the individual and the
institution. METHODS: Peer interviewing was used as part of a two-year phased
study, 2012-2013, which explored and then measured the impact of cultural
diversity on undergraduate students in a medical higher education institution in
Ireland. In phase one 16 peer interviewers were recruited to conduct 29 semi
structured interviews with fellow students. In order to evaluate the peer
interviewing process two focus group discussions were he ld and an online survey
conducted. RESULTS: Key findings were that substantial preparations in relation
to training, informed consent processes and addressing positionality are needed
if peer-interviewing is to be used. Challenges still faced included were related
to power, familiarity, trust and practical problems. However many benefits
accrued to the research, the individual interviewer and to the university.
CONCLUSIONS: A more nuanced approach to peer interviewing, that recognises
commonalities and differences across a range of attributes, is needed. While peer
interviewing has many benefits and can help reduce power differentials it does
not eliminate all challenges. As part of a larger research project and as a way
in which to get 'buy-in' from the student body and improve a collaborative
research partnership peer interviewing was extremely useful.
PMID- 26423419
TI - Sports Injury Surveillance Systems: A Review of Methods and Data Quality.
AB - BACKGROUND AND AIMS: Data from sports injury surveillance systems are a
prerequisite to the development and evaluation of injury prevention strategies.
This review aimed to identify ongoing sports injury surveillance systems and
determine whether there are gaps in our understanding of injuries in certain
sport settings. A secondary aim was to determine which of the included
surveillance systems have evaluated the quality of their data, a key factor in
determining their usefulness. METHODS: A systematic search was carried out to
identify (1) publications presenting methodological details of sports injury
surveillance systems within clubs and organisations; and (2) publications
describing quality evaluations and the quality of data from these systems. Data
extracted included methodological details of the surveillance systems, methods
used to evaluate data quality, and results of these evaluations. RESULTS:
Following literature search and review, a total of 15 sports injury surveillance
systems were identified. Data relevant to each aim were summarised descriptively.
Most systems were found to exist within professional and elite sports.
Publications concerning data quality were identified for seven (47%) systems.
Validation of system data through comparison with alternate sources has been
undertaken for only four systems (27%). CONCLUSIONS: This review identified a
shortage of ongoing injury surveillance data from amateur and community sport
settings and limited information about the quality of data in professional and
elite settings. More surveillance systems are needed across a range of sport
settings, as are standards for data quality reporting. These efforts will enable
better monitoring of sports injury trends and the development of sports safety
strategies.
PMID- 26423422
TI - Late administration of murine CTLA-4 blockade prolongs CD8-mediated anti-tumor
effects following stimulatory cancer immunotherapy.
AB - We have demonstrated that immunostimulatory therapies such as interleukin-2 (IL
2) and anti-CD40 (alphaCD40) can be combined to deliver synergistic anti-tumor
effects. While this strategy has shown success, efficacy varies depending on a
number of factors including tumor type and severe toxicities can be seen. We
sought to determine whether blockade of negative regulators such as cytotoxic T
lymphocyte antigen-4 (CTLA-4) could simultaneously prolong CD8(+) T cell
responses and augment T cell anti-tumor effects. We devised a regimen in which
anti-CTLA-4 was administered late so as to delay contraction and minimize
toxicities. This late administration both enhanced and prolonged CD8 T cell
activation without the need for additional IL-2. The quality of the T cell
response was improved with increased frequency of effector/effector memory
phenotype cells along with improved lytic ability and bystander expansion. This
enhanced CD8 response translated to improved anti-tumor responses both at the
primary and metastatic sites. Importantly, toxicities were not exacerbated with
combination. This study provides a platform for rational design of immunotherapy
combinations to maximize anti-tumor immunity while minimizing toxicities.
PMID- 26423423
TI - Downstream mediators of the intratumoral interferon response suppress antitumor
immunity, induce gemcitabine resistance and associate with poor survival in human
pancreatic cancer.
AB - The cancer microenvironment allows tumor cells to evade immune surveillance
through a variety of mechanisms. While interferon-gamma (IFNgamma) is central to
effective antitumor immunity, its effects on the microenvironment are not as
clear and have in some cancers been shown to induce immune checkpoint ligands.
The heterogeneity of these responses to IFNgamma remains poorly characterized in
desmoplastic malignancies with minimal inflammatory cell infiltration, such as
pancreatic cancer (PC). Thus, the IFNgamma response within and on key cells of
the PC microenvironment was evaluated. IFNgamma induced expression of human
leukocyte antigen (HLA) class I and II on PC cell lines, primary pancreatic
cancer epithelial cells (PPCE) and patient-derived tumor-associated stroma,
concomitant with an upregulation of PDL1 in the absence of CD80 and CD86
expression. As expected, IFNgamma also induced high levels of CXCL10 from all
cell types. In addition, significantly higher levels of CXCL10 were observed in
PC specimens compared to those from chronic pancreatitis, whereby intratumoral
CXCL10 concentration was an independent predictor of poor survival.
Immunohistochemical analysis revealed a subset of CXCR3-positive cancer cells in
over 90 % of PC specimens, as well as on a subset of cultured PC cell lines and
PPCE, whereby exposure to CXCL10 induced resistance to the chemotherapeutic
gemcitabine. These findings suggest that IFNgamma has multiple effects on many
cell types within the PC microenvironment that may lead to immune evasion,
chemoresistance and shortened survival.
PMID- 26423424
TI - A retrospective study of the incidence, clinical characteristics, identification,
and antimicrobial susceptibility of bacteremic isolates of Acinetobacter
ursingii.
AB - BACKGROUND: Acinetobacter ursingii bacteremia is rarely reported. We investigated
the incidence and clinical features of A. ursingii bacteremia, performance of the
identification system, and antimicrobial susceptibility of the isolates.
Acinetobacter ursingii bacteremia patients were compared with A. baumannii
bacteremia patients. METHODS: In this 9-year retrospective study, A. ursingii was
identified using 16S rRNA and 16S-23S rRNA internal transcribed spacer sequence
analysis. The performances of the Vitek 2, Phoenix, and matrix-assisted laser
desorption ionization time-of-flight (MALDI-TOF) mass spectrometer systems for
identifying isolates were tested. Pulsed-field gel electrophoresis (PFGE) was
used to determine the clonality of the isolates. The minimal inhibitory
concentrations of the antimicrobials were determined using the Vitek 2 system.
RESULTS: Nineteen patients were identified. Acinetobacter ursingii was noted in
1.5-5.2 % of all Acinetobacter bacteremia cases. For the PFGE analysis, two
isolates had smeared DNA, two had 93 % similarity, and 15 had similarity <80 %.
Among 16 patients with complete medical records, 10 (62.5 %) had no identifiable
source of A. ursingii bacteremia. Most patients (n = 12) had underlying malignant
disease. Patients with A. ursingii bacteremia had lower Acute Physiology and
Chronic Health Evaluation II scores than those with A. baumannii bacteremia
(median [interquartile range], 17.1 [10.0-24.7] vs. 24.9 [14.6-35.1]). Patients
with A. ursingii bacteremia were also less likely admitted to the intensive care
unit than patients with A. baumannii bacteremia (18.8 % vs 63.5 %, p value <
0.01). About half of the patients with A. ursingii (50.8 %) and A. baumannii
bacteremia (62.5 %) had received inappropriate antimicrobial therapy within 48 h
after bacteremia onset. However, patients with A. ursingii bacteremia had
significantly lower 14-day (6.25 % vs 29.8 %, p value = 0.04) and 28-day
mortality rates (6.25 % vs 37.3 %, p value = 0.02) than patients with A.
baumannii bacteremia. Nine isolates (47.4 %) were correctly identified as A.
ursingii and the other 10 isolates (52.6 %) were incorrectly identified as A.
lwoffii by the Vitek 2 system. The Phoenix system incorrectly identified all 19
isolates. The MALDI-TOF mass spectrometer system correctly identified all 19
isolates. All the A. ursingii isolates were resistant or showed intermediate
susceptibility to ceftriaxone and ceftazidime, but were susceptible to
levofloxacin and imipenem. CONCLUSIONS: Acinetobacter ursingii is a rare pathogen
that mostly caused primary bacteremia in patients with malignancies. Patients
with A. ursingii bacteremia had significantly lower disease severity and
mortality rates than patients with A. baumannii bacteremia.
PMID- 26423425
TI - Effect of resistance training with different frequencies and detraining on
muscular strength and oxidative stress biomarkers in older women.
AB - The aim of this study was to compare the effect of resistance training (RT)
performed with different frequencies followed by a detraining period on muscular
strength and oxidative stress (OS) biomarkers in older women. Twenty-seven
physically independent women (68.8 +/- 4.8 years, 69.1 +/- 14.3 kg, 156.0 +/- 6.5
cm, and 28.3 +/- 4.9 to kg.m(-2)) were randomly assigned to perform a RT program
for 2 or 3 days per week (G2X = 13 vs. G3X = 14) for 12 weeks followed by 12
weeks of detraining period. One repetition maximum (1RM) tests were used as
measures of muscular strength (three exercises, three attempts for each exercise,
3-5 min of rest between attempts, and 5 min of rest between exercises). Advanced
oxidized protein products (AOPP) and total radical-trapping antioxidant parameter
(TRAP) were used as oxidative stress indicators. Both groups increased muscular
strength after 12 weeks of training (P < 0.05) in chest press (G2X = +11.9 % vs.
G3X = +27.5 %, P < 0.05), knee extension (G2X = +18.4 % vs. G3X = +16.7 %, P >
0.05), and preacher curl (G2X = +37.6 % vs. G3X = +36.7 %, P > 0.05). On the
other hand, 12 weeks of detraining were not sufficient to eliminate the major
effects produced by RT on muscular strength, although a significant decrease (P <
0.05) has been observed for chest press (G3X = -9.1 % vs. G2X = -10.2 %, P >
0.05), knee extension (G2X = -14.9 % vs. G3X = -12.1 %, P > 0.05), and preacher
curl (G2X = -20.5 % vs. G3X = -17.4 %, P > 0.05). Pre- to post-training, both
groups showed significant (P < 0.05) increases in TRAP (G2X = +6.9 % vs. G3X =
+15.1 %) with no statistical significant difference between the groups (P >
0.05), and the scores remained elevated compared to pre-training after 12 weeks
of detraining. AOPP was not changed by RT or detraining (P > 0.05). The results
suggest that a 12-week RT program with a frequency of 2 days per week may be
sufficient to improve muscular strength and OS in older women and detraining for
12 weeks does not completely reverse the changes induced by RT.
PMID- 26423426
TI - Clinical and serologic features of primary Sjogren's syndrome concomitant with
autoimmune hemolytic anemia: a large-scale cross-sectional study.
AB - Autoimmune hemolytic anemia (AIHA) is an uncommon but clinically significant
disorder in primary Sjogren's syndrome (pSS). Among 565 pSS patients hospitalized
in Peking University People's Hospital from January 2000 to March 2013, 16
patients were diagnosed with AIHA (2.8% prevalence). AIHA presented at the onset
of pSS without overt sicca symptoms in 3 of the 16 patients. Primary biliary
cirrhosis (PBC) was more prevalent in the patients with SS-AIHA than in those
without (p = 0.007). Edema, fever, and liver involvement occurred significantly
more frequently in pSS patients with AIHA than those without AIHA (p = 0.035, p =
0.029, p = 0.024, respectively). The pSS patients with AIHA were more vulnerable
to leukopenia and thrombocytopenia than those without AIHA (p = 0.004 and p =
0.001, respectively). Additionally, the levels of complement component 3 (C3) and
complement component 4 (C4) were significantly lower in the SS-AIHA group (p =
0.008 and p = 0.037, respectively). Taken together, our results indicate that pSS
should be considered in the differential diagnosis of AIHA, even in the absence
of sicca symptoms. Among pSS patients, the existence of PBC, cytopenia, or
hypocomplementemia suggests a higher risk of suffering from AIHA.
PMID- 26423427
TI - Resveratrol prevents renal lipotoxicity in high-fat diet-treated mouse model
through regulating PPAR-alpha pathway.
AB - Resveratrol (RSV) has beneficial effects on renal diseases, but its underlying
mechanisms are still unclear. In the present study, we investigate the
renoprotective effects of RSV on obesity-related renal diseases and clarify the
potential mechanisms. Male C57BL/6J mice were fed with high-fat diet (HFD) with
or without 400 mg/kg RSV treatment for 12 weeks. Feeding HFD induced renal
injuries, but treating them with RSV significantly decreased glomerular volume (p
< 0.05), glycogen (p < 0.01) and collagen (p < 0.05) in renal tissues. Although
slightly changed body weight and fasting blood glucose, RSV attenuated renal
dysfunction, including decreased levels of blood urea nitrogen (p < 0.05), urea
protein (p < 0.01), and microalbuminuria (p < 0.01). Furthermore, RSV treatment
markedly reduced gene expression of tumor necrosis factor (TNF)-alpha,
interleukin (IL)-6 and inducible nitric oxide synthase (iNOS) (all p < 0.05), 4
Hydroxynonenal expression (p < 0.01), and lipid accumulation. Mechanistically,
RSV enhanced the expression of lipolytic genes, peroxisome proliferator-activated
receptor (PPAR)-alpha (p < 0.001), carnitine palmitoyltransferase (CPT)-1 (p <
0.05), and medium-chain acyl-coenzyme A dehydrogenase (MCAD) (p < 0.01), but had
no effect on lipogenic genes, PPAR-gamma and sterol regulatory element-binding
protein (SREBP)-1c. RSV also obviously increased renal PPAR-alpha protein
expression (p < 0.001) and the phosphorylation of AMPK level. Collectively, these
results support the therapeutic effects of RSV on high-fat diet-induced renal
damages at least partially through targeting on PPAR-alpha signaling pathway.
PMID- 26423428
TI - A call for new attitudes on infection, vaccination, and childhood stroke.
PMID- 26423429
TI - Migraine and cryptogenic stroke: The clot thickens.
PMID- 26423430
TI - Delivery of epilepsy care to adults with intellectual and developmental
disabilities.
AB - Epilepsy is common in people with intellectual and developmental disabilities
(IDD). In adulthood, patients with IDD and epilepsy (IDD-E) have neurologic,
psychiatric, medical, and social challenges compounded by fragmented and limited
care. With increasing neurologic disability, there is a higher frequency of
epilepsy, especially symptomatic generalized and treatment-resistant epilepsies.
The causes of IDD-E are increasingly recognized to be genetic based on
chromosomal microarray analysis to identify copy number variants, gene panels
(epilepsy, autism spectrum disorder, intellectual disability), and whole-exome
sequencing. A specific genetic diagnosis may guide care by pointing to comorbid
disorders and best therapy. Therapy to control seizures should be individualized,
with drug selection based on seizure types, epilepsy syndrome, concomitant
medications, and comorbid disorders. There are limited comparative antiepileptic
drug data in the IDD-E population. Vagus nerve and responsive neural stimulation
therapies and resective surgery should be considered. Among the many comorbid
disorders that affect patients with IDD-E, psychiatric and sleep disorders are
common but often unrecognized and typically not treated. Transition from holistic
and coordinated pediatric to adult care is often a vulnerable period.
Communication among adult health care providers is complex but essential to
ensure best care when these patients are seen in outpatient, emergency room, and
inpatient settings. We propose specific recommendations for minimum care
standards for people with IDD-E.
PMID- 26423431
TI - Age-specific association of migraine with cryptogenic TIA and stroke: Population
based study.
AB - OBJECTIVE: To determine whether there is an association between previous migraine
and cryptogenic TIA or ischemic stroke at older ages. METHODS: We determined the
age-specific associations of history of migraine and Trial of Org 10172 in Acute
Stroke Treatment (TOAST) subtype of TIA and ischemic stroke in a population-based
cohort study (Oxford Vascular Study; 2002-2012). RESULTS: Among 1,810 eligible
patients with TIA or ischemic stroke, 668 (36.9%) had cryptogenic events, of whom
187 (28.0%) had previous migraine. Migraine was more commonly associated with
cryptogenic events than with those of known etiology (odds ratio [OR] 1.73, 95%
confidence interval [CI] 1.38-2.16, p < 0.0001; cardioembolic 2.00, 1.50-2.66, p
< 0.0001; large artery 1.75, 1.20-2.53, p = 0.003; small vessel 1.32, 0.95-1.83,
p = 0.096). The association of migraine with cryptogenic events was independent
of age, sex, and all measured vascular risk factors (RFs) (adjusted OR 1.68, 1.33
2.13, p < 0.0001) and was strongest at older ages (<55 years, OR 1.11, 0.55-2.23;
55-64 years, 1.48, 0.83-2.63; >=65 years, 1.81, 1.39-2.36) and in patients
without vascular RFs (0 RFs OR 2.62, 1.33-5.15; 1 RF 2.01, 1.35-3.01; 2 RFs 1.80,
1.21-2.68; 3 RFs 1.21, 0.71-2.07; 4 RFs 0.92, 0.28-2.99). Results were consistent
for migraine with or without aura and for analyses excluding TIA or stratified by
sex or vascular territory of event. CONCLUSIONS: In this population-based study
of stroke etiology stratified by age, migraine was most strongly associated with
cryptogenic TIA and ischemic stroke, particularly at older ages, suggesting a
causal role or a shared etiology.
PMID- 26423432
TI - Structural MRI substrates of cognitive impairment in neuromyelitis optica.
AB - OBJECTIVE: To identify the clinical and structural MRI markers for predicting
cognitive impairment (CI) in patients with neuromyelitis optica (NMO). METHODS:
Fifty-four patients with NMO and 27 healthy controls underwent extensive
neuropsychological testing and multimodal 3.0T MRI. The patient group was
classified as CI or cognitively preserved (CP), using a criterion of <=1.5 SD on
at least 2 cognitive domains. MRI measurements included white matter (WM) lesion
volume, gray matter (GM), WM, and deep GM (DGM) volume, cortical thickness, and
the severity and extent of WM tract diffusion metric alterations based on
fractional anisotropy and mean, axial, and radial diffusivity. Groups were
compared using a multivariate general linear model, and clinical and MRI
measurements were related to average cognition z scores by partial correlations
and a stepwise linear regression model. RESULTS: Twenty-six patients with NMO
(48.2%) were classified as CI and showed WM tract diffusion abnormalities,
particularly increased radial diffusivity, and GM especially DGM atrophy compared
with healthy controls. Patients classified as CP also showed alterations of WM
tract diffusion but without significant GM atrophy. Compared with the CP group,
patients with CI demonstrated a lower level of education and decreased
hippocampal volume. In the whole patient group, average cognition z scores were
best predicted by the level of education and hippocampal volume (R(2) = 0.46, p <
0.001). CONCLUSION: In patients with NMO, WM tract integrity disruption was
identified in both CP and CI groups. GM atrophy, particularly in the DGM, was
only found in the CI group. Hippocampal volume is the main MRI predictor of
cognition in NMO.
PMID- 26423433
TI - Comment: Improving the care of people with epilepsy and intellectual
disabilities.
PMID- 26423435
TI - Artificial fish skin of self-powered micro-electromechanical systems hair cells
for sensing hydrodynamic flow phenomena.
AB - Using biological sensors, aquatic animals like fishes are capable of performing
impressive behaviours such as super-manoeuvrability, hydrodynamic flow 'vision'
and object localization with a success unmatched by human-engineered
technologies. Inspired by the multiple functionalities of the ubiquitous lateral
line sensors of fishes, we developed flexible and surface-mountable arrays of
micro-electromechanical systems (MEMS) artificial hair cell flow sensors. This
paper reports the development of the MEMS artificial versions of superficial and
canal neuromasts and experimental characterization of their unique flow-sensing
roles. Our MEMS flow sensors feature a stereolithographically fabricated polymer
hair cell mounted on Pb(Zr(0.52)Ti(0.48))O3 micro-diaphragm with floating bottom
electrode. Canal-inspired versions are developed by mounting a polymer canal with
pores that guide external flows to the hair cells embedded in the canal.
Experimental results conducted employing our MEMS artificial superficial
neuromasts (SNs) demonstrated a high sensitivity and very low threshold detection
limit of 22 mV/(mm s(-1)) and 8.2 um s(-1), respectively, for an oscillating
dipole stimulus vibrating at 35 Hz. Flexible arrays of such superficial sensors
were demonstrated to localize an underwater dipole stimulus. Comparative
experimental studies revealed a high-pass filtering nature of the canal
encapsulated sensors with a cut-off frequency of 10 Hz and a flat frequency
response of artificial SNs. Flexible arrays of self-powered, miniaturized, light
weight, low-cost and robust artificial lateral-line systems could enhance the
capabilities of underwater vehicles.
PMID- 26423434
TI - Infection, vaccination, and childhood arterial ischemic stroke: Results of the
VIPS study.
AB - OBJECTIVES: Minor infection can trigger adult arterial ischemic stroke (AIS) and
is common in childhood. We tested the hypotheses that infection transiently
increases risk of AIS in children, regardless of stroke subtype, while
vaccination against infection is protective. METHODS: The Vascular Effects of
Infection in Pediatric Stroke study is an international case-control study that
prospectively enrolled 355 centrally confirmed cases of AIS (29 days-18 years
old) and 354 stroke-free controls. To determine prior exposure to infections and
vaccines, we conducted parental interviews and chart review. RESULTS: Median
(interquartile range) age was 7.6 years for cases and 9.3 for controls (p =
0.44). Infection in the week prior to stroke, or interview date for controls, was
reported in 18% of cases, vs 3% of controls, conferring a 6.3-fold increased risk
of AIS (p < 0.0001); upper respiratory infections were most common. Prevalence of
preceding infection was similar across stroke subtypes: arteriopathic,
cardioembolic, and idiopathic. Use of vasoactive cold medications was similarly
low in both groups. Children with some/few/no routine vaccinations were at higher
stroke risk than those receiving all or most (odds ratio [OR] 7.3, p = 0.0002).
In an age-adjusted multivariate logistic regression model, independent risk
factors for AIS included infection in the prior week (OR 6.3, p < 0.0001),
undervaccination (OR 8.2, p = 0.0004), black race (compared to white; OR 1.9, p =
0.009), and rural residence (compared to urban; OR 3.0, p = 0.0003). CONCLUSIONS:
Infection may act as a trigger for childhood AIS, while routine vaccinations
appear protective. Hence, efforts to reduce the spread of common infections might
help prevent stroke in children.
PMID- 26423436
TI - Structural symmetry in evolutionary games.
AB - In evolutionary game theory, an important measure of a mutant trait (strategy) is
its ability to invade and take over an otherwise-monomorphic population.
Typically, one quantifies the success of a mutant strategy via the probability
that a randomly occurring mutant will fixate in the population. However, in a
structured population, this fixation probability may depend on where the mutant
arises. Moreover, the fixation probability is just one quantity by which one can
measure the success of a mutant; fixation time, for instance, is another. We
define a notion of homogeneity for evolutionary games that captures what it means
for two single-mutant states, i.e. two configurations of a single mutant in an
otherwise-monomorphic population, to be 'evolutionarily equivalent' in the sense
that all measures of evolutionary success are the same for both configurations.
Using asymmetric games, we argue that the term 'homogeneous' should apply to the
evolutionary process as a whole rather than to just the population structure. For
evolutionary matrix games in graph-structured populations, we give precise
conditions under which the resulting process is homogeneous. Finally, we show
that asymmetric matrix games can be reduced to symmetric games if the population
structure possesses a sufficient degree of symmetry.
PMID- 26423437
TI - DyNAMiC Workbench: an integrated development environment for dynamic DNA
nanotechnology.
AB - Dynamic DNA nanotechnology provides a promising avenue for implementing
sophisticated assembly processes, mechanical behaviours, sensing and computation
at the nanoscale. However, design of these systems is complex and error-prone,
because the need to control the kinetic pathway of a system greatly increases the
number of design constraints and possible failure modes for the system. Previous
tools have automated some parts of the design workflow, but an integrated
solution is lacking. Here, we present software implementing a three 'tier' design
process: a high-level visual programming language is used to describe systems, a
molecular compiler builds a DNA implementation and nucleotide sequences are
generated and optimized. Additionally, our software includes tools for analysing
and 'debugging' the designs in silico, and for importing/exporting designs to
other commonly used software systems. The software we present is built on many
existing pieces of software, but is integrated into a single package-accessible
using a Web-based interface at http://molecular-systems.net/workbench. We hope
that the deep integration between tools and the flexibility of this design
process will lead to better experimental results, fewer experimental design
iterations and the development of more complex DNA nanosystems.
PMID- 26423438
TI - Emergent behavioural phenotypes of swarming models revealed by mimicking a
frustrated anti-ferromagnet.
AB - Self-propelled particle (SPP) models are often compared with animal swarms.
However, the collective animal behaviour observed in experiments often leaves
considerable unconstrained freedom in the structure of a proposed model.
Essentially, multiple models can describe the observed behaviour of animal swarms
in simple environments. To tackle this degeneracy, we study swarms of SPPs in non
trivial environments as a new approach to distinguish between candidate models.
We restrict swarms of SPPs to circular (periodic) channels where they polarize in
one of two directions (like spins) and permit information to pass through windows
between neighbouring channels. Co-alignment between particles then couples the
channels (anti-ferromagnetically) so that they tend to counter-rotate. We study
channels arranged to mimic a geometrically frustrated anti-ferromagnet and show
how the effects of this frustration allow us to better distinguish between SPP
models. Similar experiments could therefore improve our understanding of
collective motion in animals. Finally, we discuss how the spin analogy can be
exploited to construct universal logic gates, and therefore swarming systems that
can function as Turing machines.
PMID- 26423439
TI - Optics of cone photoreceptors in the chicken (Gallus gallus domesticus).
AB - Vision is the primary sensory modality of birds, and its importance is evident in
the sophistication of their visual systems. Coloured oil droplets in the cone
photoreceptors represent an adaptation in the avian retina, acting as long-pass
colour filters. However, we currently lack understanding of how the optical
properties and morphology of component structures (e.g. oil droplet,
mitochondrial ellipsoid and outer segment) of the cone photoreceptor influence
the transmission of light into the outer segment and the ultimate effect they
have on receptor sensitivity. In this study, we use data from
microspectrophotometry, digital holographic microscopy and electron microscopy to
inform electromagnetic models of avian cone photoreceptors to quantitatively
investigate the integrated optical function of the cell. We find that pigmented
oil droplets primarily function as spectral filters, not light collection
devices, although the mitochondrial ellipsoid improves optical coupling between
the inner segment and oil droplet. In contrast, unpigmented droplets found in
violet-sensitive cones double sensitivity at its peak relative to other cone
types. Oil droplets and ellipsoids both narrow the angular sensitivity of single
cone photoreceptors, but not as strongly as those in human cones.
PMID- 26423440
TI - Patterns of recruitment and injury in a heterogeneous airway network model.
AB - In respiratory distress, lung airways become flooded with liquid and may collapse
due to surface-tension forces acting on air-liquid interfaces, inhibiting gas
exchange. This paper proposes a mathematical multiscale model for the mechanical
ventilation of a network of occluded airways, where air is forced into the
network at a fixed tidal volume, allowing investigation of optimal recruitment
strategies. The temporal response is derived from mechanistic models of
individual airway reopening, incorporating feedback on the airway pressure due to
recruitment. The model accounts for stochastic variability in airway diameter and
stiffness across and between generations. For weak heterogeneity, the network is
completely ventilated via one or more avalanches of recruitment (with airways
recruited in quick succession), each characterized by a transient decrease in the
airway pressure; avalanches become more erratic for airways that are initially
more flooded. However, the time taken for complete ventilation of the network
increases significantly as the network becomes more heterogeneous, leading to
increased stresses on airway walls. The model predicts that the most peripheral
airways are most at risk of ventilation-induced damage. A positive-end-expiratory
pressure reduces the total recruitment time but at the cost of larger stresses
exerted on airway walls.
PMID- 26423441
TI - Optimal allocation of the limited oral cholera vaccine supply between endemic and
epidemic settings.
AB - The World Health Organization (WHO) recently established a global stockpile of
oral cholera vaccine (OCV) to be preferentially used in epidemic response
(reactive campaigns) with any vaccine remaining after 1 year allocated to endemic
settings. Hence, the number of cholera cases or deaths prevented in an endemic
setting represents the minimum utility of these doses, and the optimal risk
averse response to any reactive vaccination request (i.e. the minimax strategy)
is one that allocates the remaining doses between the requested epidemic response
and endemic use in order to ensure that at least this minimum utility is
achieved. Using mathematical models, we find that the best minimax strategy is to
allocate the majority of doses to reactive campaigns, unless the request came
late in the targeted epidemic. As vaccine supplies dwindle, the case for reactive
use of the remaining doses grows stronger. Our analysis provides a lower bound
for the amount of OCV to keep in reserve when responding to any request. These
results provide a strategic context for the fulfilment of requests to the
stockpile, and define allocation strategies that minimize the number of OCV doses
that are allocated to suboptimal situations.
PMID- 26423443
TI - Liposheres as a Novel Carrier for Lipid Based Drug Delivery: Current and Future
Directions.
AB - Researchers are facing challenges to develop robust formulation and to enhance
the bioavailability of poorly water-soluble drugs towards clinical applications.
The development of new drug molecule alone is not adequate to assure ample
pharmacotherapy of various diseases. Considerable results obtained from in vitro
studies are not supported by in vivo data due to inadequate plasma drug
concentrations. This may occur due to limited drug solubility and absorption. To
resolve these problems, development of new drug delivery systems will be a
promising approach. One of the promising pharmaceutical strategies is the use of
lipospheres drug delivery system to deliver the poorly water-soluble drugs.
Therefore, the present review described the methodology for manufacturing of
lipospheres and factors influencing the formulation to deliver the drugs to the
targeted site. Apart from that, this review also enlisted briefly the various
applications of liposphers in medical and biomedical fields and critically
discussed the recent patent system.
PMID- 26423442
TI - In vitro degradability, bioactivity and primary cell responses to bone cements
containing mesoporous magnesium-calcium silicate and calcium sulfate for bone
regeneration.
AB - Mesoporous calcium sulfate-based bone cements (m-CSBC) were prepared by
introducing mesoporous magnesium-calcium silicate (m-MCS) with specific surface
area (410.9 m2 g(-1)) and pore volume (0.8 cm3 g(-1)) into calcium sulfate
hemihydrate (CSH). The setting time of the m-CSBC was longer with the increase of
m-MCS content while compressive strength decreased. The degradation ratio of m
CSBC increased from 48.6 w% to 63.5 w% with an increase of m-MCS content after
soaking in Tris-HCl solution for 84 days. Moreover, the m-CSBC containing m-MCS
showed the ability to neutralize the acidic degradation products of calcium
sulfate and prevent the pH from dropping. The apatite could be induced on m-CSBC
surfaces after soaking in SBF for 7 days, indicating good bioactivity. The
effects of the m-CSBC on vitamin D3 sustained release behaviours were
investigated. It was found that the cumulative release ratio of vitamin D3 from
the m-CSBC significantly increased with the increase of m-MCS content after
soaking in PBS (pH = 7.4) for 25 days. The m-CSBC markedly improved the cell
positive responses, including the attachment, proliferation and differentiation
of MC3T3-E1 cells, suggesting good cytocompatibility. Briefly, m-CSBC with good
bioactivity, degradability and cytocompatibility might be an excellent biocement
for bone regeneration.
PMID- 26423444
TI - Evaluating the effectiveness of common disinfectants at preventing the
propagation of Mycobacterium spp. isolated from zebrafish.
AB - Mycobacteriosis is a bacterial disease that is common in captive, wild and
research fish. There is no one causative agent of mycobacteriosis, as several
strains and species of Mycobacterium have been identified in zebrafish. With
increased usage and investment in wild-type and mutant zebrafish strains,
considerable value is placed on preserving zebrafish health. One control measure
used to prevent mycobacterial spread within and between zebrafish facilities is
egg disinfection. Here we investigate the effectiveness of three disinfectants
[chlorine bleach, hydrogen peroxide, and povidone-iodine (PVPI)] commonly
included in egg disinfection protocols for laboratory fish as well as aquaculture
fish and compare the knockdown effect of these treatments on Mycobacterium spp.
in vitro. Despite current usage, comparison of these disinfection regimes'
abilities to prevent mycobacterial growth has not been tested. We found that the
germicidal effect of different disinfectants varies by Mycobacterium spp.
Hydrogen peroxide was the least effective disinfectant, followed by unbuffered
chlorine bleach, which is commonly used to disinfect embryos in zebrafish
facilities. Disinfection with 25ppm PVPI for 5min was very effective, and may be
an improved alternative to chlorine bleach for embryo disinfection. Results from
this study can be utilized by laboratory fish facilities in order to prevent the
spread of mycobacteriosis in research fish.
PMID- 26423445
TI - Effect of the ionic product of bioglass 60s on osteoblastic activity in canines.
AB - BACKGROUND: The objective of the present study was to evaluate the effect of the
ionic product (IP) of BG60S on osteoblastic activity. The following media groups
were created: DMEM, which is formed by osteoblasts in basal medium; IP DMEM,
which is formed by osteoblasts in IP with basal medium; OST, which is formed by
osteoblasts in osteogenic medium; and IP OST, which is formed by osteoblasts in
IP with osteogenic medium. The osteoblasts were cultivated in an incubator at 37
degrees C and 5 % CO2 for 7, 14 and 21 days. After each period, the alkaline
phosphatase (AP) activity, mineralised area per field and expression of osterix
(OSX), bone sialoprotein (BSP), osteonectin (ON) and osteocalcin (OC) were
evaluated by reverse transcription (RT)-PCR. RESULTS: The IP significantly
increased the AP activity in the IP DMEM group at 7 and 14 days and reduced the
AP activity in the IP OST group at 14 and 21 days relative to their respective
controls (DMEM and OST). The groups that received the IP displayed a significant
increase in the percentage of mineralised area per field and more advance
maturation of the extracellular matrix relative to those that did not receive IP.
The IP significantly increased the expression of OSX, BSP and ON in osteoblast
cultures maintained in IP DMEM compared with the control (DMEM) for the majority
of studied periods. In osteogenic medium, IP also significantly increased OSX,
BSP, ON and OC expression compared with the control (OST) for the majority of
studied periods. CONCLUSIONS: The IP of BG60S alters the gene expression of
canine osteoblasts, favouring the synthesis and mineralisation of the
extracellular matrix.
PMID- 26423447
TI - The binding selectivity of vonoprazan (TAK-438) to the gastric H+, K+ -ATPase.
AB - BACKGROUND: The gastric H(+) ,K(+) -ATPase is the preferred target for acid
suppression. Until recently, the only drugs that effectively inhibited this
ATPase were the proton pump inhibitors (PPIs). PPIs are acid-activated prodrugs
that require acid protection. Once acid-activated, PPIs bind to cysteines of the
ATPase, resulting in covalent, long-lasting inhibition. The short plasma half
life of PPIs and continual de novo synthesis of the H(+) ,K(+) -ATPase result in
difficulty controlling night-time acid secretion. A new alternative to PPIs is
the pyrrolo-pyridine, vonoprazan (TAK-438), a potassium-competitive acid blocker
(PCAB) that does not require acid protection. In contrast to other PCABs,
vonoprazan has a long duration of action, resulting in 24-h control of acid
secretion, a high pKa of 9.37 and high affinity (Ki = 3.0 etamol/L). AIM: To
determine binding selectivity of vonoprazan for the gastric H(+) ,K(+) -ATPase
and to explain its slow dissociation. METHODS: Gastric gland and parietal cell
binding of vonoprazan was determined radiometrically. Molecular modelling
explained the slow dissociation of vonoprazan from the H(+) ,K(+) -ATPase.
RESULTS: Vonoprazan binds selectively to the parietal cell, independent of acid
secretion. Vonoprazan binds in a luminal vestibule between the surfaces of
membrane helices 4, 5 and 6. Exit of the drug to the lumen is hindered by asp137
and asn138 in the loop between TM1 and TM2, which presents an electrostatic
barrier to movement of the sulfonyl group of vonoprazan. This may explain its
slow dissociation from the H(+) ,K(+) -ATPase and long-lasting inhibition.
CONCLUSION: The binding model provides a template for design of novel potassium
competitive acid blockers.
PMID- 26423448
TI - Ferritin heavy chain mediates the protective effect of heme oxygenase-1 against
oxidative stress.
AB - The phenomenon that heme oxygenase-1 (HO-1) protects cell from injury yet its
enzymatic product, iron, may facilitate generation of free radical has been long
puzzling. Here we establish a functional connection between ferritin heavy chain
(FHC) and HO-1. In human lupus nephritis HO-1 and FHC are colocalized within the
glomeruli. In rodent anti-Thy1 (thymocyte antigen 1) induced glomerulonephritis,
heme oxygenase blockade lowers the expression of FHC and accelerates mesangial
cell death. Stimulation of heme oxygenase in cultured rat mesangial cell enhances
its resistance to hydrogen peroxide, whereas FHC knockdown by RNA interference
compromises this salutary effect. RNA interference of HO-1 makes the cell more
susceptible to hydrogen peroxide, which can be rescued by forced expression of
wild-type FHC but not mutants that lose the capacity of iron storage and
ferroxidase activity. Phosphorylation of JunD was not sustained in these cells.
Microarray analysis identifies four candidate transcriptional factors that may
regulate the HO-1-induced transcription of FHC. Our results support the role of
FHC in neutralizing the iron toxicity as well as mediating the protective effect
of HO-1 in response to oxidative stress.
PMID- 26423449
TI - The effects of anesthesia on the morphoproteomic expression of head and neck
squamous cell carcinoma: a pilot study.
AB - The prognosis and disease-free survival rates for head and neck squamous cell
carcinoma (HNSCC) have remained relatively stagnant for the last several decades.
Moreover, as is the case with other malignancies, locoregional recurrence and
distant metastasis are all too common even after seemingly successful oncologic
surgery and adjuvant therapy. Recently, increased focus has been placed on
understanding the influence of perioperative factors on tumor cell behavior and
surgical outcomes. More specifically, emerging research suggests that anesthetic
agents may play a role in cancer recurrence by interacting with prosurvival
protein signaling pathways which harden tumor cells against oncologic treatments.
In the present pilot study, we tested the hypothesis that inhalational anesthesia
and total intravenous anesthesia (TIVA) exert differential effects on the
proteomic expression of HNSCC. Ten patients with previously untreated oral cavity
or oropharyngeal HNSCC were randomized to receive either sevoflurane and
remifentanil or propofol and remifentanil for the duration of their respective
surgeries. Morphoproteomic analysis using 10 pro-oncogenic protein markers was
performed on both pre- and postanesthesia tumor samples to qualitatively grade
changes in protein expression. The results of this analysis demonstrated
differential expression of several protein markers. Specifically, the exposure to
sevoflurane but not TIVA resulted in a statistically significant increase in the
expression of cytoplasmic hypoxia-inducible factor-2alpha (P = 0.049) and nuclear
p-p38 mitogenic-activated protein kinase (P = 0.041). This study represents one
of the first to evaluate the effects of anesthesia on the molecular biology of
HNSCC in vivo, and the results suggest that the exposure to sevoflurane may
increase the expression of pro-oncogenic protein markers in HNSCC tumor cells.
PMID- 26423446
TI - Longitudinal Weight Loss Patterns and their Behavioral and Demographic
Associations.
AB - BACKGROUND: Identification of weight change patterns may allow tailored
interventions to improve long-term weight loss. PURPOSE: To identify patterns of
weight change over 18 months, and assess participant characteristics and
intervention adherence factors associated with weight change patterns in a sample
of 359 overweight/obese adults. METHODS: Weight loss (0-6 months) was achieved
with reduced energy intake and increased physical activity (PA). Maintenance (7
18 months) provided adequate energy to maintain weight and continued PA. RESULTS:
Latent profile analysis identified three weight change profiles. During weight
loss/maintenance, participants in profiles 2 and 3 (18-month weight loss ~14 %)
attended more behavioral sessions and performed more PA compared with profile 1
(18-month weight loss <1 %). Self-efficacy for both weight management and
exercise barriers were higher in profiles 2 and 3 compared with profile 1
following weight loss and during maintenance. CONCLUSION: Weight change patterns
can be identified and are associated with both participant characteristics and
intervention adherence.
PMID- 26423450
TI - Correlation between prenatal ultrasound and postmortem findings in 1029 fetuses
following termination of pregnancy.
AB - OBJECTIVE: A prenatal ultrasound examination and a postmortem examination provide
the basis for correct diagnosis in fetuses terminated due to congenital
anomalies. The aim of this study was to correlate fetal anomalies detected by
ultrasound examination with those identified at autopsy following termination of
pregnancy (TOP) over a 30-year period, and to evaluate the correlation between
findings at different gestational ages and assess these trends over time.
METHODS: The study group consisted of 1029 TOPs performed over a 30-year period,
from 1985 to 2014. The gestational age ranged between 11 and 33 weeks. Prenatal
ultrasound examinations were performed at the National Center for Fetal Medicine,
St Olavs Hospital, Trondheim, Norway. Autopsies were performed at the Department
of Pathology and Medical Genetics at the same hospital or a collaborating
hospital. RESULTS: There was full agreement between ultrasound and autopsy
findings in 88.1% (907/1029) of TOPs, and the main diagnosis was correct in 97.9%
(1007/1029). When comparing the 15-year period of 2000-2014 with that of 1985
1999, the difference in the rates of full agreement and agreement in the main
diagnosis was statistically significant. In 1.3% (13/1029) of cases, ultrasound
findings were not confirmed at autopsy. There were no false-positive diagnoses
leading to TOP. Throughout the 30-year period, there was an increase in early
TOPs, whereas late TOPs declined. CONCLUSIONS: Our study demonstrates that there
is a clear correlation between ultrasound and autopsy findings, which is
continuously improving. Despite this high correlation, there is reason to
continue the practice of validation to ensure the safety of the diagnostic
process leading to TOP. The trend towards an earlier termination emphasizes the
necessity of such a practice. Copyright (c) 2015 ISUOG. Published by John Wiley &
Sons Ltd.
PMID- 26423451
TI - Outer retinal tubulations response to anti-VEGF treatment.
AB - AIM: To review the longitudinal changes of outer retinal tubulations (ORTs) in
wet age-related macular degeneration (AMD) and their response to anti-vascular
endothelial growth factor (VEGF) therapy by spectral-domain optical coherence
tomography (SD-OCT), and to correlate these observations with disease activity,
presence or absence of fluid, and patients' demographics. METHODS: Retrospective
study of wet AMD eyes treated with anti-VEGF agents and showing ORTs on SD-OCT,
and the patients' fellow eye with wet AMD but without ORTs. RESULTS: Fifty-one
wet AMD eyes from 31 patients diagnosed and treated for wet AMD were included in
the review and analysis of data; 33 eyes showed ORTs at baseline, while 18 fellow
eyes had no ORTs. During a median follow-up treatment period of 11 months, 23
eyes had stable ORTs and 10 eyes had ORT changes. Among the 10 eyes with ORTs
changes, ORTs collapsed during anti-VEGF treatment in 5 eyes but then reappeared
within 12 months after stopping treatment. In two eyes, ORTs increased in size
during anti-VEGF treatment, while in two other eyes ORTs collapsed without any
treatment. In a single eye, ORTs collapsed within 10 months of no treatment and
did not reappear upon recurrence of fluid. Eyes with ORTs tended to have lower
visual acuity than eyes with no ORTs due to greater disruption of the external
limiting membrane in the fovea. CONCLUSIONS: ORTs documented by SD-OCT may
exhibit multiple types of longitudinal changes, such as collapse, recurrence or
enlargement, which could be associated with anti-VEGF treatment or spontaneous.
Some ORTs may have a vascular component or may be vascular in nature, considering
their response to anti-VEGF treatment, while other ORTs are likely composed only
of degenerating photoreceptor cells and may collapse independently from anti-VEGF
treatments.
PMID- 26423452
TI - Corneal endothelium in xeroderma pigmentosum: clinical specular microscopy study.
AB - AIMS: Xeroderma pigmentosum is a condition caused due to a defective DNA repair
mechanism when exposed to ultraviolet radiation. Many of the patients with this
disorder develop severely oedematous cornea with varying degrees of anterior
corneal haze, which necessitates a full-thickness keratoplasty or selective
endothelial keratoplasty. Presence of corneal oedema suggests that these patients
have a dysfunctional endothelium. The purpose of this study is to evaluate the
corneal endothelium in the patients with xeroderma pigmentosum when clinical
specular microscopy was feasible. METHODS: Thirteen patients with classic skin
changes of xeroderma pigmentosum were included in the study conducted during
January 2010-December 2012. An age-matched group of 13 volunteers were included
as controls who were emmetropes without any history of ocular or systemic
illness. Corneal endothelium was assessed using specular microscopy from the
central clear area of cornea. RESULTS: The mean age of the patients with
xeroderma pigmentosum was 16.6+/-7.2 years and that of the controls was 17.4+/
6.9 years (p=0.78). The number of analysed cells and endothelial cell density
were significantly higher in controls (p<0.001), whereas the average cell area,
coefficient of variation of cell area and maximum cell area were significantly
higher in xeroderma pigmentosum (p<=0.007). CONCLUSIONS: The specular microscopic
findings in patients with xeroderma pigmentosum are suggestive of an accelerated
endothelial cell loss. It is pertinent that the treating physicians must be
involved in emphasising proper ocular protection from ultraviolet radiation to
prevent avoidable blindness from xeroderma pigmentosum.
PMID- 26423453
TI - Maharashtra government launches mental health programme to reduce suicide in
farmers.
PMID- 26423454
TI - Importance of "default" intraoperative ventilator settings.
PMID- 26423455
TI - Effect of a nasal clip on inhaling a sufficient cortico steroid powder dose.
PMID- 26423456
TI - Does superficial fat affect metabolite concentrations determined by MR
spectroscopy with water referencing?
AB - It has recently been reported in this journal that local fat depots produce a
sizable frequency-dependent signal attenuation in magnetic resonance spectroscopy
(MRS) of the brain. If of a general nature, this effect would question the use of
internal reference signals for quantification of MRS and the quantitative use of
MRS as a whole. Here, it was attempted to verify this effect and pinpoint the
potential causes by acquiring data with various acquisition settings, including
two field strengths, two MR scanners from different vendors, different water
suppression sequences, RF coils, localization sequences, echo times, and
lipid/metabolite phantoms. With all settings tested, the reported effect could
not be reproduced, and it is concluded that water referencing and quantitative
MRS per se remain valid tools under common acquisition conditions.
PMID- 26423457
TI - Genetic inhibition of JNK3 ameliorates spinal muscular atrophy.
AB - Mutation of the Survival Motor Neuron 1 (SMN1) gene causes spinal muscular
atrophy (SMA), an autosomal recessive neurodegenerative disorder that occurs in
early childhood. Degeneration of spinal motor neurons caused by SMN deficiency
results in progressive muscle atrophy and death in SMA. The molecular mechanism
underlying neurodegeneration in SMA is unknown. No treatment is available to
prevent neurodegeneration and reduce the burden of illness in SMA. We report that
the c-Jun NH2-terminal kinase (JNK) signaling pathway mediates neurodegeneration
in SMA. The neuron-specific isoform JNK3 is required for neuron degeneration
caused by SMN deficiency. JNK3 deficiency reduces degeneration of cultured
neurons caused by low levels of SMN. Genetic inhibition of JNK pathway in vivo by
Jnk3 knockout results in amelioration of SMA phenotype. JNK3 deficiency prevents
the loss of spinal cord motor neurons, reduces muscle degeneration, improves
muscle fiber thickness and muscle growth, improves motor function and overall
growth and increases lifespan of mice with SMA that shows a systemic rescue of
phenotype by a SMN-independent mechanism. JNK3 represents a potential (non-SMN)
therapeutic target for the treatment of SMA.
PMID- 26423458
TI - Genome-wide disruption of 5-hydroxymethylcytosine in a mouse model of autism.
AB - The autism spectrum disorders (ASD) comprise a broad group of behaviorally
related neurodevelopmental disorders affecting as many as 1 in 68 children. The
hallmarks of ASD consist of impaired social and communication interactions,
pronounced repetitive behaviors and restricted patterns of interests. Family,
twin and epidemiological studies suggest a polygenetic and epistatic
susceptibility model involving the interaction of many genes; however, the
etiology of ASD is likely to be complex and include both epigenetic and
environmental factors. 5-hydroxymethylcytosine (5hmC) is a novel environmentally
sensitive DNA modification that is highly enriched in post-mitotic neurons and is
associated with active transcription of neuronal genes. Here, we used an
established chemical labeling and affinity purification method coupled with high
throughput sequencing technology to generate a genome-wide profile of striatal
5hmC in an autism mouse model (Cntnap2(-/-) mice) and found that at 9 weeks of
age the Cntnap2(-/-) mice have a genome-wide disruption in 5hmC, primarily in
genic regions and repetitive elements. Annotation of differentially
hydroxymethylated regions (DhMRs) to genes revealed a significant overlap with
known ASD genes (e.g. Nrxn1 and Reln) that carried an enrichment of neuronal
ontological functions, including axonogenesis and neuron projection
morphogenesis. Finally, sequence motif predictions identified associations with
transcription factors that have a high correlation with important genes in
neuronal developmental and functional pathways. Together, our data implicate a
role for 5hmC-mediated epigenetic modulation in the pathogenesis of autism and
represent a critical step toward understanding the genome-wide molecular
consequence of the Cntnap2 mutation, which results in an autism-like phenotype.
PMID- 26423460
TI - On Race and Time.
AB - Arousal is known to shape time perception, and heightened arousal causes one to
perceive that time has slowed (i.e., a given length of time feels longer than it
actually is). The current experiments illustrate that among White people who
experience arousal when contemplating race (specifically those for whom appearing
biased is an ongoing concern), time perception slows when they observe faces of
Black men. We asked participants to judge the duration of presentation for faces
of White and Black men (shown for periods ranging from 300 to 1,200 ms) relative
to a standard duration of 600 ms. Evidence of bias emerged when White
participants concerned with bias saw faces of Black men (e.g., durations of less
than 600 ms were perceived as being greater than 600 ms). The current findings
have implications for intergroup interactions in which timing is essential-for
example, length of job interviews, police officers' perception of the length of
an encounter and when force should be initiated, and doctors' perception of the
length of medical encounters. Racially biased time perception is a new form of
implicit bias, one exerted at the perceptual level.
PMID- 26423459
TI - Use of the HPRT gene to study nuclease-induced DNA double-strand break repair.
AB - Understanding the mechanisms of chromosomal double-strand break repair (DSBR)
provides insight into genome instability, oncogenesis and genome engineering,
including disease gene correction. Research into DSBR exploits rare-cutting
endonucleases to cleave exogenous reporter constructs integrated into the genome.
Multiple reporter constructs have been developed to detect various DSBR pathways.
Here, using a single endogenous reporter gene, the X-chromosomal disease gene
encoding hypoxanthine phosphoribosyltransferase (HPRT), we monitor the relative
utilization of three DSBR pathways following cleavage by I-SceI or CRISPR/Cas9
nucleases. For I-SceI, our estimated frequencies of accurate or mutagenic non
homologous end-joining and gene correction by homologous recombination are 4.1,
1.5 and 0.16%, respectively. Unexpectedly, I-SceI and Cas9 induced markedly
different DSBR profiles. Also, using an I-SceI-sensitive HPRT minigene, we show
that gene correction is more efficient when using long double-stranded DNA than
single- or double-stranded oligonucleotides. Finally, using both endogenous HPRT
and exogenous reporters, we validate novel cell cycle phase-specific I-SceI
derivatives for investigating cell cycle variations in DSBR. The results obtained
using these novel approaches provide new insights into template design for gene
correction and the relationships between multiple DSBR pathways at a single
endogenous disease gene.
PMID- 26423462
TI - Introduction.
PMID- 26423463
TI - Bad science and how to avoid it, a movement analysis perspective: Study design,
statistics and publication ethics.
PMID- 26423461
TI - Decoding Visual Location From Neural Patterns in the Auditory Cortex of the
Congenitally Deaf.
AB - Sensory cortices of individuals who are congenitally deprived of a sense can
exhibit considerable plasticity and be recruited to process information from the
senses that remain intact. Here, we explored whether the auditory cortex of
congenitally deaf individuals represents visual field location of a stimulus-a
dimension that is represented in early visual areas. We used functional MRI to
measure neural activity in auditory and visual cortices of congenitally deaf and
hearing humans while they observed stimuli typically used for mapping visual
field preferences in visual cortex. We found that the location of a visual
stimulus can be successfully decoded from the patterns of neural activity in
auditory cortex of congenitally deaf but not hearing individuals. This is
particularly true for locations within the horizontal plane and within peripheral
vision. These data show that the representations stored within neuroplastically
changed auditory cortex can align with dimensions that are typically represented
in visual cortex.
PMID- 26423464
TI - The relationship between health and cell-mediated immunity measured in ecology:
Phytohaemagglutinin skin-swelling test mirrors blood cellular composition.
AB - The phytohaemagglutinin (PHA) skin-swelling test, a common ecological method for
measuring immune responsiveness, uses a subcutaneous injection of PHA to induce
an inflammatory response with metrically measurable swelling. Both the
immunological basis of this response and the role of pre-exposure physiology
remain poorly understood, however, preventing predictions of costs and benefits
of immunity investments revealed by the test and their relationship to life
history traits. In this study, we measure PHA-triggered tissue swelling, cellular
infiltration into inflamed tissue, and haematological changes in zebra finches
Taeniopygia guttata, with the aim of identifying those cell types involved in
activation of PHA-induced skin swelling. We show that the inflammation underlying
the swelling response is dependent on initial haematological state and alters the
composition of circulating leukocytes. Injection of PHA decreased heterophil and
monocyte frequency and increased basophil frequency, suggesting changes in
leukocyte trafficking and haematopoiesis. Higher initial basophil and lymphocyte
frequencies in peripheral blood were associated with increased swelling. High pre
treatment blood lymphocyte levels led to intense lymphocyte migration into
inflamed tissue, while high initial basophil levels resulted in lower cellular
infiltration. Our results show two possible directions in the association between
pre-exposure health and swelling response: (i) a lymphocyte-based pathway that
leads to higher responsiveness in high-quality healthy individuals capable of
higher energy and resource investment, or (ii) higher responsiveness in diseased
individuals with initially elevated basophil levels and pre-activated immunity.
Haematological investigation, therefore, facilitates interpretation of PHA skin
swelling test results in ecological immunology, explaining ca. 20 % of variation
in skin-swelling data. J. Exp. Zool. 323A: 767-777, 2015. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26423465
TI - Complementary and Alternative Health Practices in the Rehabilitation Nursing.
AB - This article discusses the connection between the Theory of Integral Nursing and
the use of complementary and alternative medicine to rehabilitation nursing.
Complementary and alternative health practices refers to methods, practices, and
modalities that are outside of the realm of biomedicine. Some of the types of
treatments and practices that are considered to be alternative include folk
medicine, herbal medicine, homeopathy, faith healing, massage, energy healing,
acupuncture and acupressure, supplements, aromatherapy, and music therapy. The
Theory of Integral Nursing is explained in some detail. Components of self-care,
nursing-based complementary and alternative medicine practices, and supplement
alternatives for pain and antidepressant medications used in the rehabilitation
setting are also reviewed.
PMID- 26423466
TI - Survey of anal sphincter dysfunction using anal manometry in patients with fecal
incontinence: a possible guide to therapy.
AB - BACKGROUND: Despite the surge of new medical and surgical approaches to treat
fecal incontinence, the types of sphincter abnormalities in patients with
incontinence have not been well characterized. We aimed to categorize anal
sphincter dysfunction using anorectal manometry in patients with fecal
incontinence as a potential guide for improved treatment. METHODS: A
retrospective review of 162 consecutive patients with fecal incontinence referred
for anorectal manometry was performed. Resting anal pressure and maximal squeeze
pressure were considered as measures of internal anal sphincter and external anal
sphincter function respectively. RESULTS: Mean age of the patients was 63 years
(13-89); females (81.5%) and males (18.5%). 74% of the patients had sphincter
dysfunction on anorectal manometry. Internal anal sphincter dysfunction was
present in 62% patients vs. external anal sphincter dysfunction present in 44%
patients. 80% females had abnormal manometry vs. 44% in males (P<0.0001).
Internal anal sphincter dysfunction was present in 68% females vs. 37% in males
(P=0.0026). CONCLUSIONS: Overall, abnormal anorectal manometry studies revealed
that internal anal sphincter dysfunction is the most common finding, alone or in
combination with external anal sphincter dysfunction. We suggest that anorectal
manometry may be important to delineate anal sphincter function prior to using
newer therapeutic mechanical devices. Future studies using pharmacological agents
to increase internal anal sphincter tone may be of clinical importance. Finally,
the classification of fecal incontinence based on the type of sphincter
dysfunction may be an improved guide in the selection of newer agents in treating
fecal incontinence.
PMID- 26423467
TI - Partially desulfated heparin modulates the interaction between anti
protamine/heparin antibodies and platelets.
AB - Protamine (PRT) is the standard drug to neutralise heparin. PRT/heparin complexes
induce an immune response similar to that observed in heparin-induced
thrombocytopenia (HIT). Partially desulfated heparin (ODSH) was shown to
interfere with anti-platelet factor 4/heparin antibodies (Abs), which are
responsible for HIT. In this study, we analyse the impact of ODSH on the
interaction between anti-PRT/heparin Abs and platelets. The ability of ODSH to
prevent anti-PRT/heparin Ab-induced platelet destruction in vivo was investigated
using the NOD/SCID mouse model. ODSH improved platelet survival in the presence
of PRT, heparin and anti-PRT/heparin Abs (median platelet survival after 300
minutes (min) with 20 ug/ml ODSH: 75%, range 70-81% vs without ODSH: 49%, range
44-59%, p=0.006). Furthermore, when ODSH was applied 60 min after Ab injection
platelet survival was improved (median platelet survival after 300 min with ODSH:
83%, range 77-93% vs without ODSH: 59%, range 29-61%, p=0.02). In in vitro
experiments ODSH inhibited platelet activation at concentrations >16 ug/mL
(p<0.001), as well as PRT/heparin complex binding to platelets (mean fluorescence
intensity [MFI] without ODSH: 85 +/- 14 vs with ODSH: 15 +/- 0.6, p=0.013). ODSH
also displaced pre-bound complexes from the platelet surface (MFI without ODSH:
324 +/- 43 vs with 32 ug/ml ODSH: 53 +/- 9, p<0.001). While interfering with
platelet activation by anti-PRT/heparin Abs, up to a concentration of 16 ug/ml,
ODSH had only minimal impact on neutralisation of heparin by PRT. In conclusion,
our study shows that ODSH is able to inhibit platelet activation and destruction
suggesting a potential clinical use to reduce anti-PRT/heparin Ab-mediated
adverse effects.
PMID- 26423470
TI - Water availability predicts forest canopy height at the global scale.
AB - The tendency of trees to grow taller with increasing water availability is common
knowledge. Yet a robust, universal relationship between the spatial distribution
of water availability and forest canopy height (H) is lacking. Here, we created a
global water availability map by calculating an annual budget as the difference
between precipitation (P) and potential evapotranspiration (PET) at a 1-km
spatial resolution, and in turn correlated it with a global H map of the same
resolution. Across forested areas over the globe, Hmean increased with P-PET,
roughly: Hmean (m) = 19.3 + 0.077*(P-PET). Maximum forest canopy height also
increased gradually from ~ 5 to ~ 50 m, saturating at ~ 45 m for P-PET > 500 mm.
Forests were far from their maximum height potential in cold, boreal regions and
in disturbed areas. The strong association between forest height and P-PET
provides a useful tool when studying future forest dynamics under climate change,
and in quantifying anthropogenic forest disturbance.
PMID- 26423471
TI - In response to: 'Folic acid levels in some food staples in Ireland are on the
decline: implications for passive folic acid intakes?' (Kelly et al.
2016;38(2):265-9).
PMID- 26423473
TI - The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide
population-based study.
AB - OBJECTIVE: Pituitary adenomas (PA) are among the most common human neoplasms. To
describe the epidemiology and assess the disease burden of clinically significant
PAs, population-based studies are needed. Iceland has a small well-defined
population. The aim of this study is to describe the epidemiology of PAs in
Iceland over an expanded period of time. DESIGN: This is a retrospective
observational study, including all PAs diagnosed in Iceland from 1955 to 2012.
METHODS: Extensive clinical information was gathered in a database. Prevalence
rates for all PA subtypes were calculated along with standardized incidence rates
(SIR). Sex ratios and relationships with adenoma size, age, and symptoms were
assessed. RESULTS: We identified 471 individuals: 190 men and 281 women. Total
prevalence in 2012 was 115.57/100, 000, prolactinomas were most prevalent
(54.37/100, 000) followed by non-functioning adenomas (NFPAs) (42.32/100 ,000).
Throughout the period, NFPAs were most common (43.0%) followed by prolactinomas
(39.9%) and 11.3% had acromegaly and 5.7% Cushing's disease. Women are diagnosed
younger with smaller adenomas. Total SIR has increased significantly and is now
5.8/100 000 per year. CONCLUSION: In this nationwide study spanning six decades,
we have confirmed PAs rising prevalence and incidence rates noted in recent
studies. We demonstrated higher overall prevalence and incidence rates than ever
previously recorded with an increasing predominance of NFPAs, which is not
explained by incidental findings alone. There is a relationship with the
introduction of imaging modalities, but the vast majority of patients are
symptomatic at diagnosis. This underlines the importance of increased awareness,
education, and appropriate allocation of resources for this growing group of
patients.
PMID- 26423474
TI - Is Adult-Onset ADHD a Distinct Entity?
PMID- 26423475
TI - Toward Improved Risk Prediction in Individuals at High Risk of Psychotic
Disorders.
PMID- 26423476
TI - Getting Past Proof of Concept For New Treatments.
PMID- 26423477
TI - Addressing Patients' Psychic Pain.
PMID- 26423478
TI - Domestic Violence Awareness.
PMID- 26423479
TI - Reproductive Psychiatry: The Gap Between Clinical Need and Education.
PMID- 26423480
TI - Rorschach Inkblot Invasion of Pop Culture.
PMID- 26423481
TI - Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible
Mechanisms in Depression.
AB - OBJECTIVE: The authors conducted a systematic review and meta-analysis of
ketamine and other N-methyl-d-aspartate (NMDA) receptor antagonists in the
treatment of major depression. METHOD: Searches of MEDLINE, PsycINFO, and other
databases were conducted for placebo-controlled, double-blind, randomized
clinical trials of NMDA antagonists in the treatment of depression. Primary
outcomes were rates of treatment response and transient remission of symptoms.
Secondary outcomes included change in depression symptom severity and the
frequency and severity of dissociative and psychotomimetic effects. Results for
each NMDA antagonist were combined in meta-analyses, reporting odds ratios for
dichotomous outcomes and standardized mean differences for continuous outcomes.
RESULTS: Ketamine (seven trials encompassing 147 ketamine-treated participants)
produced a rapid, yet transient, antidepressant effect, with odds ratios for
response and transient remission of symptoms at 24 hours equaling 9.87 (4.37
22.29) and 14.47 (2.67-78.49), respectively, accompanied by brief psychotomimetic
and dissociative effects. Ketamine augmentation of ECT (five trials encompassing
89 ketamine-treated participants) significantly reduced depressive symptoms
following an initial treatment (Hedges' g=0.933) but not at the conclusion of the
ECT course. Other NMDA antagonists failed to consistently demonstrate efficacy;
however, two partial agonists at the NMDA coagonist site, d-cycloserine and
rapastinel, significantly reduced depressive symptoms without psychotomimetic or
dissociative effects. CONCLUSIONS: The antidepressant efficacy of ketamine, and
perhaps D-cycloserine and rapastinel, holds promise for future glutamate
modulating strategies; however, the ineffectiveness of other NMDA antagonists
suggests that any forthcoming advances will depend on improving our understanding
of ketamine's mechanism of action. The fleeting nature of ketamine's therapeutic
benefit, coupled with its potential for abuse and neurotoxicity, suggest that its
use in the clinical setting warrants caution.
PMID- 26423482
TI - Brief CBT and Suicide Risk: Ruling Out Nonspecific Effects of Individual Therapy.
PMID- 26423483
TI - Response to Stankiewicz et al.
PMID- 26423484
TI - Cardiac Effects of Methylphenidate.
PMID- 26423485
TI - Response to Roose and Rutherford.
PMID- 26423486
TI - A Case of a Depressed Patient With Major Titanium Cranial Base Reconstruction
Successfully Treated by ECT.
PMID- 26423492
TI - CORRECTION. In the Wake of National Trauma: Psychological Reactions Following the
Charlie Hebdo Terror Attack.
PMID- 26423493
TI - APA Council Reports.
AB - At the fall component meetings of the American Psychiatric Association in Crystal
City, Va., September 9-12, 2015, the APA councils heard reports from their
components. Following are summaries of the activities of the councils and their
components.
PMID- 26423494
TI - Scaling Up Nature: Large Area Flexible Biomimetic Surfaces.
AB - The fabrication and advanced function of large area biomimetic superhydrophobic
surfaces (SHS) and slippery lubricant-infused porous surfaces (SLIPS) are
reported. The use of roll-to-roll nanoimprinting techniques enabled the
continuous fabrication of SHS and SLIPS based on hierarchically wrinkled
surfaces. Perfluoropolyether hybrid molds were used as flexible molds for roll-to
roll imprinting into a newly designed thiol-ene based photopolymer resin coated
on flexible polyethylene terephthalate films. The patterned surfaces exhibit
feasible superhydrophobicity with a water contact angle around 160 degrees
without any further surface modification. The SHS can be easily converted into
SLIPS by roll-to-roll coating of a fluorinated lubricant, and these surfaces have
outstanding repellence to a variety of liquids. Furthermore, both SHS and SLIPS
display antibiofouling properties when challenged with Escherichia coli K12
MG1655. The current article describes the transformation of artificial biomimetic
structures from small, lab-scale coupons to low-cost, large area platforms.
PMID- 26423495
TI - Comparative Evaluation of Fracture Resistance and Mode of Failure of Zirconia and
Titanium Abutments with Different Diameters.
AB - AIM: The purpose of the current study was to compare the fracture resistance and
mode of failure of zirconia and titanium abutments with different diameters.
MATERIALS AND METHODS: Fourteen groups of abutments including prefabricated
zirconia, copy-milled zirconia and titanium abutments of an implant system (XiVE,
Dentsply) were prepared in different diameters. An increasing vertical load was
applied to each specimen until failure occurred. Fracture resistance was measured
in each group using the universal testing machine. Moreover, the failure modes
were studied and categorized as abutment screw fracture, connection area
fracture, abutment body fracture, abutment body distortion, screw distortion and
connection area distortion. Groups were statistically compared using univariate
and post-hoc tests. The level of statistical significance was set at 5%. RESULTS:
Fabrication method (p = 0.03) and diameter (p < 0.001) had significant effect on
the fracture resistance of abutments. Fracture resistance of abutments with 5.5
mm diameter was higher than other diameters (p < 0.001). The observed modes of
failure were dependent on the abutment material as well. All of the prefabricated
titanium abutments fractured within the abutment screw. Abutment screw
distortion, connection area fracture, and abutment body fracture were the common
failure type in other groups. CONCLUSION: Diameter had a significant effect on
fracture resistance of implant abutments, as abutments with greater diameters
were more resistant to static loads. Copy-milled abutments showed lower fracture
resistance as compared to other experimental groups. CLINICAL SIGNIFICANCE:
Although zirconia abutments have received great popularity among clinicians and
even patients selecting them for narrow implants should be with caution.
PMID- 26423496
TI - Comparison of Antimicrobial Activity between Chemical Disinfectants on
Contaminated Orthodontic Pliers.
AB - AIM: To compare the antimicrobial activity of the chemical substances--70%
isopropyl alcohol, 2% glutaraldehyde (GTA) and 0.25% peracetic acid (PAA) in
disinfecting orthodontic pliers contaminated in vitro with Streptococcui mutani,
Staphylococci aureui and Candida albicani. MATERIALS AND METHODS: Distal end
cutter pliers were divided into five groups: group 1 (negative control-
sterilized pliers), group 2 (positive control--sterilized plier, subsequently
contaminated), group 3 (disinfected with 70% isopropyl alcohol, friction method),
group 4 (disinfected with 2% GTA, immersion method for 30 minutes), group 5
(disinfected with 0.25% peracetic acid (PAA), immersion method for 10 minutes).
After the pliers were treated with one disinfectant and submitted to
microbiological evaluation (by counting colony forming units), they were
submitted to the same cleansing, sterilizing and contaminating processes, and
were used in the following groups (crossover and washout study). The two-factor
analysis of variance (ANOVA) test, followed by the Tukey test, was used to
compare the groups. RESULTS: The results showed that there was no statistically
significant difference between the three tested disinfectants. CONCLUSION:
Although there were no statistically significant differences between the
disinfectants, the chemical agents 2% glutaraldehyde and 0.25% PAA were effective
in inhibiting the growth of the three microorganisms tested; however, 70%
isopropyl alcohol was unable to completely eliminate S. aureui. CLINICAL
SIGNIFICANCE: The chemical substances 2% glutaraldehyde and 0.25% PAA completely
eliminated the microorganisms tested.
PMID- 26423497
TI - Antimicrobial Activity and pH of Calcium Hydroxide and Zinc Oxide Nanoparticles
Intracanal Medication and Association with Chlorhexidine.
AB - AIM: To evaluate pH and antibacterial activity of pastes with calcium hydroxide
[Ca(OH)2] and zinc oxide (ZnO) microparticles (micro) or nanoparticles (nano) and
association with 0.4% chlorhexidine against Enterococcus faecalis. MATERIALS AND
METHODS: The following pastes were analyzed: Ca(OH)2/ZnO micro, (2) Ca(OH)2/ZnO
nano, (3) Ca(OH)2/ ZnO micro + 0.4% chlorhexidine, (4) Ca(OH)2/ZnO nano + 0.4%
chlorhexidine. Antibacterial activity against E. faecalis was evaluated by agar
diffusion test. The direct contact test on planktonic cells of E. faecalis was
performed for 30 and 60 seconds. Root canals from bovine teeth were filled with
the pastes and pH was evaluated after 1, 7, 14, 21, 30 and 60 days. The data
obtained were submitted to the statistical tests analysis of variance (ANOVA) and
Tukey or Kruskal-Wallis and Dunn test, with a 5% significance level. RESULTS:
Calcium hydroxide and zinc oxide nano, and the pastes with 0.4% chlorhexidine
were more effective in agar diffusion test. In the direct contact test, the
pastes with chlorhexidine showed the highest effect after 30 seconds. All pastes
eliminated E. faecalis after 60 seconds. All pastes promoted an increase in pH.
The highest increase in pH was observed with nanoparticle medications after 1 and
7 days (p < 0.05). After this period, the pastes presented similar pH increase.
CONCLUSION: It was concluded that calcium hydroxide and zinc oxide nanoparticles
promoted greater initial alkalinization. The antimicrobial activity of the pastes
against E. faecalis is favored by the association with chlorhexidine. CLINICAL
SIGNIFICANCE: Although nanoparticles of calcium hydroxide and zinc oxide promoted
antibacterial effect, the activity against E. faecalis is favored by association
with chlorhexidine.
PMID- 26423498
TI - Evaluation of Bone Thickness and Density in the Lower Incisors' Region in Adults
with Different Types of Skeletal Malocclusion using Cone-beam Computed
Tomography.
AB - OBJECTIVES: To evaluate the bone thickness and density in the lower incisors'
region in orthodontically untreated adults, and to examine any possible
relationship between thickness and density in different skeletal patterns using
cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The CBCT records of
48 patients were obtained from the archive of orthodontic department comprising
three groups of malocclusion (class I, II and III) with 16 patients in each
group. Using OnDemand 3D software, sagittal sections were made for each lower
incisor. Thicknesses and densities were measured at three levels of the root
(cervical, middle and apical regions) from the labial and lingual sides. Accuracy
and reliability tests were undertaken to assess the intraobserver reliability and
to detect systematic error. Pearson correlation coefficients were calculated and
one-way analysis of variance (ANOVA) was employed to detect significant
differences among the three groups of skeletal malocclusion. RESULTS: Apical
buccal thickness (ABT) in the four incisors was higher in class II and I patients
than in class III patients (p < 0.05). There were significant differences between
buccal and lingual surfaces at the apical and middle regions only in class II and
III patients. Statistical differences were found between class I and II patients
for the cervical buccal density (CBD) and between class II and III patients for
apical buccal density (ABD). Relationship between bone thickness and density
values ranged from strong at the cervical regions to weak at the apical regions.
CONCLUSIONS: Sagittal skeletal patterns affect apical bone thickness and density
at buccal surfaces of the four lower incisors' roots. Alveolar bone thickness and
density increased from the cervical to the apical regions.
PMID- 26423499
TI - Is It Possible to induce Artificial Caries-affected Dentin using the Same
Protocol to Primary and Permanent Teeth?
AB - AIM: This in vitro study compared the mineral loss of natural and artificially
created caries-affected dentin in primary and permanent teeth using the same
protocol to induce caries lesions. MATERIALS AND METHODS: Twenty molars
presenting natural occlusal dentin caries lesions (10 primary-PriC and 10 perma
nent-PermC; control group), and 20 sound molars (10 primary -PripH and 10
permanent-PermpH; experimental group), were selected. Occlusal cavities were
prepared in teeth of the experimental group that were submitted to pH-cycling for
14 days to simulate caries-affected dentin. All specimens were longitudinally
sectioned and prepared in order to obtain Knoop micro-hardness values from 15 to
250 urn depth, starting in bottom of center of natural lesions or cavities. The
microhardness (KHN) data were submitted to three-way repeated measures analysis
of variance (ANOVA) and Tukey's tests (alpha = 0.05). RESULTS: Considering all
depths, there was no statistically significant differences (p > 0.05) between the
mineral loss of the control (PriC = 30.9 +/- 6.4 and PermC = 40.8 +/- 8.6) and
experimental (PripH = 27.3 +/- 11.1 and PermpH = 35.5 +/- 14.0) groups, neither
between primary and permanent teeth. CONCLUSION: The mineral loss of the
artificially-created caries-affected dentin is similar to that from naturally
developed dentin caries lesions. CLINICAL SIGNIFICANCE: The pH-cycling model may
be a suitable method to simulate caries-affected dentin in both permanent and
primary teeth.
PMID- 26423500
TI - In vivo Evaluation of Proximal Resin Composite Restorations performed using Three
Different Matrix Systems.
AB - OBJECTIVE: The aim of this in vivo study was to radiographically evaluate the
proximal contour of composite resin restorations performed using different matrix
systems. MATERIALS AND METHODS: Patients with premolars needing class II type
resin composite restorations involving the marginal ridge were selected. Thirty
premolars were selected and randomly divided into three groups (n = 10 each) to
receive restorations using different matrix systems: group 1: metal matrix
coupled to a carrier matrix and wood wedge (G1-MMW); group 2: sectioned and
precontoured metal matrix and elastic wedge (G2-SME); and group 3: a polyester
strip and reflective wedge (G3-PMR). After the restorative procedure, bitewing
radiographs were performed and analyzed by three calibrated professionals. The
quality of the proximal contact and marginal adaptation of the proximal surfaces
was classified as either correct or incorrect (undercontour/overcontour).
RESULTS: The Pearson Chi-square statistical test (alpha = 5%) revealed a
statistically difference between frequencies of correct and incorrect
restorations (alpha(2) = 6.787, p < 0.05). The group G2 SME produced a higher
frequency of correct proximal contours (90%), while G1-MMW and G3-PMR had a ratio
of 40% correct and 60% incorrect contours respectively. CONCLUSION: None of the
matrix systems was able to prevent the formation of incorrect proximal contours;
however, the sectioned and precontoured metal matrix/elastic wedge configuration
provided better results as compared to the other groups.
PMID- 26423501
TI - An Evaluation of Inter- and Intraobserver Reliability of Cone-beam Computed
Tomography- and Two Dimensional-based Interpretations of Maxillary Canine
Impactions using a Panel of Orthodontically Trained Observers.
AB - OBJECTIVES: To assess intra- and interobserver agreement when evaluating
maxillary impacted canines using cone beam computed tomography (CBCT) and two
dimensional (2D) images through a panel of orthodontically trained observers.
MATERIALS AND METHODS: An adult skull with permanent dentition was employed to
perform 15 simulated maxillary canine impactions. Two sets of 2D and three
dimensional (3D) radiographic images were acquired. A panel of assessors
including 11 PhD and MSc postgraduate orthodontic students evaluated maxillary
impacted canines using a standard questionnaire with 11 categorical variables.
Kappa (K) statistics as well as Krippendorff's alpha (alpha) coefficients were
used for the analysis of reliability. RESULTS: A high level of intraobserver
agreement was found for both the CBCT- and 2D-based interpretations. The 11
observers demonstrated a higher interobserver agreement for the CBCT-based
interpretations than that of the 2D-based interpretations (alpha = 0.68 and 0.38
respectively). The employed 3D classifications canines was found to be reliable
among observers on CBCT images for the labiopalatal position (K = 0.87),
mesiodistal position, vertical position, labiopalatal inclination and mesiodistal
inclination (alpha = 0.95, 0.83, 0.84 and 0.92 respectively). The 2D-based
interpretations were not in agreement among the 11 observers, except for the
mesiodistal position (alpha = 0.88) and mesiodistal inclination (alpha = 0.88).
CONCLUSION: The intraobserver agreement was high for both the 2D- and the CBCT
based interpretations. The interobserver agreement for the CBCT-based
interpretations was remarkably higher than that of the 2D-based interpretations.
The utilized CBCT-based 3D classifications for the location and inclination of
maxillary impacted canines were found reliable among observers.
PMID- 26423502
TI - The Efficacy of Calcium Hydroxide Powder mixed with 0.2% Chlorhexidine
Digluconate or mixed with Normal Saline as Intracanal Medicament in the Treatment
of Apical Periodontitis.
AB - AIM: To compare the efficacy of calcium hydroxide powder mixed with 0.2%
chlorhexidine digluconate or mixed with normal saline as intracanal medicament in
the treatment of apical periodontitis. MATERIALS AND METHODS: Subjects were 55 in
number aged 17 to 60 years. Two-visit conventional root canal treatment was
performed on 70 teeth. The teeth were divided by randomization (balloting) into
two groups: control group and experimental group, each with 35 teeth treated with
calcium hydroxide mixed with normal saline or with 0.2% chlorhexidine digluconate
as intracanal medicament respectively. All treated teeth were evaluated
clinically and radiographically for signs and symptom of periapical infection at
specified periods postoperatively. Overall efficacy of medicament was rated based
on quality guidelines for endodontic treatment by the European Society of
Endodontology 2006. RESULTS: A postoperative favorable outcome of 97.1% in the
control group and 94.3% in the experimental group was observed at 6-month review.
This difference was not statistically significant (p > 0.05). CONCLUSION: The use
of normal saline or 0.2% chlorhexidine digluconate to mix calcium hydroxide used
as intracanal medicament during endodontic treatment resulted in high
postoperative favorable outcomes. CLINICAL SIGNIFICANCE: Efficacy of 0.2%
chlorhexidine digluconate as a vehicle for mixing calcium hydroxide as an
intracanal medicament in the treatment of apical periodontitis is comparable to
the efficacy of calcium hydroxide mixed with normal saline.
PMID- 26423503
TI - Biocorrosion of Endodontic Files through the Action of Two Species of Sulfate
reducing Bacteria: Desulfovibrio desulfuricans and Desulfovibrio fairfieldensis.
AB - AIM: This study assessed the biocorrosive capacity of two bacteria: Desulfovibrio
desulfuricans and Desulfovibrio fairfieldensis on endodontic files, as a
preliminary step in the development of a biopharmaceutical, to facilitate the
removal of endodontic file fragments from root canals. MATERIALS AND METHODS: In
the first stage, the corrosive potential of the artificial saliva medium (ASM),
modified Postgate E medium (MPEM), 2.5 % sodium hypochlorite (NaOCl) solution and
white medium (WM), without the inoculation of bacteria was assessed by immersion
assays. In the second stage, test samples were inoculated with the two species of
sulphur-reducing bacteria (SRB) on ASM and modified artificial saliva medium
(MASM). In the third stage, test samples were inoculated with the same species on
MPEM, ASM and MASM. All test samples were viewed under an infinite focus Alicona
microscope. RESULTS: No test sample became corroded when immersed only in media,
without bacteria. With the exception of one test sample between those inoculated
with bacteria in ASM and MASM, there was no evidence of corrosion. Fifty percent
of the test samples demonstrated a greater intensity of biocorrosion when
compared with the initial assays. CONCLUSION: Desulfovibrio desulfuricans and D.
fairfieldensis are capable of promoting biocorrosion of the steel constituent of
endodontic files. CLINICAL SIGNIFICANCE: This study describes the initial
development of a biopharmaceutical to facilitate the removal of endodontic file
fragments from root canals, which can be successfully implicated in endodontic
therapy in order to avoiding parendodontic surgery or even tooth loss in such
events.
PMID- 26423504
TI - Effectiveness of Oral Antiseptics on Tooth Biofilm: A Study in vivo.
AB - AIM: To evaluate the effectiveness of five different mouthwashes through
measurement of the plaque index. MATERIALS AND METHODS: Fifty subjects took part
in this blind study, randomized into blocks of five groups according to the
active ingredient of the mouthwash: CHX group (0.12% chlorhexidine gluconate),
essential oils (EO) group, cetylpyridinium chloride (CPC) group, Tri group
(triclosan) and Hamamelis virginiana (HV) group. All subjects were evaluated for
a reduction in the bacterial plaque index at 7, 14 and 21 days. RESULTS: There
was a significant reduction in the mean plaque index during the period of
evaluation (p < 0.01), and the reduction during the period of evaluation was
different between mouthwashes (p < 0.01). The reduction in the plaque index at
the end of 21 days was, in decreasing order, CHX > EO > CPC > Tri > HV.
CONCLUSION: The reduction in the plaque index during the period of evaluation was
different between the types of mouth-wash. The mouthwash containing the active
ingredient chlorhexidine was the most effective, followed by the essential oil,
cetylpyridinium chloride, triclosan and H. virginiana.
PMID- 26423505
TI - The Effects of Ionizing Radiation on the Oral Cavity.
AB - AIM: The aim of this study is to present a literature review on the effects of
the ionizing radiation from radiotherapy treatment on dental tissues. BACKGROUND:
Among the effects of increasing global life expectancy and longevity of the teeth
in the oral cavity, increasing rates of neoplastic diseases have been observed.
One of the important treatment modalities for head and neck neoplastic diseases
is radiotherapy, which uses ionizing radiation as the main mechanism of action.
Therefore, it is essential for dentists to be aware of the changes in oral and
dental tissues caused by ionizing radiation, and to develop treatment and
prevention strategies. RESULTS: In general, there is still controversy about the
effects of ionizing radiation on dental structures. However, qualitative and
quantitative changes in saliva and oral microbiota, presence of oral mucositis
and radiation-related caries are expected, as they represent the well-known side
effects of treatment with ionizing radiation. Points that still remain unclear
are the effects of radiotherapy on enamel and dentin, and on their mechanisms of
bonding to contemporary adhesive materials. CONCLUSION: Ionizing radiation has
shown important interaction with organic tissues, since more deleterious effects
have been shown on the oral mucosa, salivary glands and dentin, than on enamel.
CLINICAL SIGNIFICANCE: With the increasing number of patients with cancer seeking
dental treatment before and after head and neck radiotherapy, it is important for
dentists to be aware of the effects of ionizing radiation on the oral cavity.
PMID- 26423506
TI - Effect of Three-wall Bony Defect along Various Root Surfaces on Position of
Center of Resistance: A 3D Finite Element Analysis.
AB - INTRODUCTION: Increase in adult orthodontic patients has increased the challenges
faced by orthodontists, as they often present themselves with a varying degree of
dental and peri-odontal compromise, in which the entire orthodontic treatment
planning will revolve around maintenance and augmentation of supporting
apparatus. One of the many factors to be considered during treating an adult
patient is the height of alveolar bone and its effect on center of resistance
(CRes). MATERIALS AND METHODS: Eight 3D analytical models of upper central
incisor were designed using 'Solid Works Office Premium'. The models were
subjected to 3 and 6 mm bone loss along all four surfaces, i.e. labial, lingual,
mesial and distal. One Newton of retraction force was applied on labial surface
of tooth on model number 1, 2, 5 and 6 and 1N of distalization force was applied
to model number 3, 4, 7 and 8. The relative location of the CRes to the total
root length was taken as 41.8% of total root length from the root apex. The ANSYS
software was used to evaluate the change in CRes on all the models. RESULTS: It
was observed that CRes shifted apically from its relative location (41.8% from
apex); however, this shift was clinically insignificant. Minimum deflection of
CRes, 0.0122 mm, was seen when a distalization force was applied on model with 6
mm bone loss on distal surface, while maximum deflection of 0.0245 mm was seen
when retraction force was applied on model with 6 mm bone loss on labial surface.
CONCLUSION: The resultant displacement in position of center of resistance is
negligible; hence, there is no need of changing biomechanics during orthodontic
treatment for a tooth with three wall infrabony defects. However, it is necessary
to further study other infrabony defects like two wall or one wall defect, and
their effect on position of CRes.
PMID- 26423507
TI - Genotoxicity of Endodontic Materials: A Critical Review.
AB - Genotoxicity is an action on cell's genetic material which may affect its
integrity. This includes certain types of radiations and also certain chemical
compounds. Genotoxic materials are those with affinity to interact with DNA but
render them potentially carcinogenic or mutagenic. This review will address the
genotoxicity of endodontic irrigants, medicaments and sealers.
PMID- 26423508
TI - An Intraoperative Site-specific Bone Density Device: A Pilot Test Case.
AB - AIM: This paper reports a case of all-on-four rehabilitation where bone density
at implant sites was assessed both through preoperative computed tomographic (CT)
scans and using a micromotor working as an intraoperative bone density
measurement device. BACKGROUND: Implant-supported rehabilitation is a predictable
treatment option for tooth replacement whose success depends on the clinician's
experience, the implant characteristics and location and patient-related factors.
Among the latter, bone density is a determinant for the achievement of primary
implant stability and, eventually, for implant success. The ability to measure
bone density at the placement site before implant insertion could be important in
the clinical setting. CASE DESCRIPTION: A patient complaining of masticatory
impairment was presented with a plan calling for extraction of all her
compromised teeth, followed by implant rehabilitation. A week before surgery, she
underwent CT examination, and the bone density on the CT scans was measured. When
the implant osteotomies were created, the bone density was again measured with a
micromotor endowed with an instantaneous torque-measuring system. The implant
placement protocols were adapted for each implant, according to the
intraoperative measurements, and the patient was rehabilitated following an all
on-four immediate loading protocol. CONCLUSION: The bone density device provided
valuable information beyond that obtained from CT scans, allowing for site
specific, intraoperative assessment of bone density immediately before implant
placement and an estimation of primary stability just after implant insertion.
CLINICAL SIGNIFICANCE: Measuring jaw-bone density could help clinicians to select
implant-placement protocols and loading strategies based on site-specific bone
features.
PMID- 26423509
TI - Management of Maxillary Deformity with Segmental Osteotomy followed by Implant
Insertion in beta-Thalassemia Major Patient.
AB - AIM: The aim of this report is to present the management of the maxillary
deformity and subsequent implant therapy of a case with beta-thalassemia major.
BACKGROUND: beta-thalassemia is a hematologic disorder that results from the
abnormality of the beta-globulin chain synthesis. The best known thalassemia
induced dentofacial problem is the maxillary enlargement, and this undesirable
growth of maxilla affects not only the facial esthetics but also dental
occlusion, and leads to functional deficiency. CASE DESCRIPTION: A 16-year-old
female patient with beta-thalasse-mia major was referred with the complaints of
severe facial deformity and malocclusion, resulting in psychosocial and
functional problems for her. The dentofacial deformity was characterized by an
excessive premaxillary growth both in sagittal and vertical planes. Anterior
maxillary osteotomy was performed with bilateral canines extraction, and dental
implants were inserted to the canine regions, following bone healing.
Postoperative course was free of problems with the crown restorations in
function. Recurrence has not been occurred at 6 years follow-up. CONCLUSION: With
maintaining hemoglobin level over 10 gm/dl, correction of maxillary defects is
stable for long-term in beta-thalassemia major patient. Implant application to
these patients may lead to unforeseeable results. CLINICAL SIGNIFICANCE: Although
having some difficulties, such as overbleeding and stability problems, maxillary
enlargement can be treated by segmental osteotomies successfully in beta
thalassemia major patient. Implant failure frequency may be higher, but many
other studies are needed for determining implant survival rate in beta
thalassemia major patients.
PMID- 26423510
TI - Clinical Trials with Oncolytic Viruses: Current and Future Prospects.
AB - Reviewing the research in the field of oncolytic virus therapy (OVT) of the past
two decades, it is inspiring to see the enormous amount of success accomplished
by the scholars of this innovative therapeutic technique. Though the experimental
trials have been ongoing from 1990s, however, it took a leap forward with
approval of the clinical trials in China, 2005. The world's first oncolytic virus
to be approved by their government was adenovirus (with E1B 55K gene deletion)
for head and neck cancer therapy along with chemotherapy.
PMID- 26423511
TI - A cortical locus for anisotropic overlay suppression of stimuli presented at
fixation.
AB - Human contrast sensitivity for narrowband Gabor targets is suppressed when
superimposed on narrowband masks of the same spatial frequency and orientation
(referred to as overlay suppression), with suppression being broadly tuned to
orientation and spatial frequency. Numerous behavioral and neurophysiological
experiments have suggested that overlay suppression originates from the initial
lateral geniculate nucleus (LGN) inputs to V1, which is consistent with the broad
tuning typically reported for overlay suppression. However, recent reports have
shown narrowly tuned anisotropic overlay suppression when narrowband targets are
masked by broadband noise. Consequently, researchers have argued for an
additional form of overlay suppression that involves cortical contrast gain
control processes. The current study sought to further explore this notion
behaviorally using narrowband and broadband masks, along with a computational
neural simulation of the hypothesized underlying gain control processes in
cortex. Additionally, we employed transcranial direct current stimulation (tDCS)
in order to test whether cortical processes are involved in driving narrowly
tuned anisotropic suppression. The behavioral results yielded anisotropic overlay
suppression for both broadband and narrowband masks and could be replicated with
our computational neural simulation of anisotropic gain control. Further, the
anisotropic form of overlay suppression could be directly modulated by tDCS,
which would not be expected if the suppression was primarily subcortical in
origin. Altogether, the results of the current study provide further evidence in
support of an additional overlay suppression process that originates in cortex
and show that this form of suppression is also observable with narrowband masks.
PMID- 26423512
TI - Fulminant BCG Disease in a 7 Month Old Healthy Male Infant.
AB - A seven month old healthy male infant was brought with papular skin lesions all
over the body, which became ulcerative with increasing fever and redness within 1
week duration. On examination, Bacilli Calmette Guerin (BCG) scar was ulcerated
with discharge; infant was irritable with tachycardia and tachypnea.
Investigations revealed pancytopenia, and acid fast bacilli was positive in skin
lesions and at BCG scar site. There was progressive worsening of infant's
condition, culminating in death.
PMID- 26423514
TI - International Medical Teams of the Japan Medical Association: A Framework for
Foreign Medical Teams.
PMID- 26423513
TI - Breastfeeding Is Associated with Decreased Risk of Hospitalization among HIV
Exposed, Uninfected Kenyan Infants.
AB - BACKGROUND: Human immunodeficiency virus (HIV)-exposed uninfected (HEU) infants
are a growing population in sub-Saharan Africa, with higher morbidity and
mortality than HIV-unexposed infants. HEU infants may experience increased
morbidity due to breastfeeding avoidance. OBJECTIVES: We sought to describe the
burden and identify predictors of hospitalization among HEU infants in the first
year of life. METHODS: Using a retrospective cohort of HIV-infected mothers and
their HEU infants in Nairobi, Kenya, we identified infants who were HIV
uninfected at birth and were followed monthly until their last negative HIV test,
death, loss to follow-up, or study exit at 1 year of age. Incidence, timing, and
reason for hospitalization was assessed overall as well as stratified by feeding
method. Predictors of first infectious disease hospitalization were identified
using competing risk regression, with HIV acquisition and death as competing
risks. RESULTS: Among 388 infants, 113 hospitalizations were reported (35/100
infant-years [the combined years of observation contributed by all infants in the
study]; 95% confidence interval [CI], 29-42). Ninety hospitalizations were due to
1 or more infectious diseases (26/100 infant-years; 95% CI, 21-32)-primarily
pneumonia (n = 40), gastroenteritis (n = 17), and sepsis (n = 14). Breastfeeding
was associated with decreased risk of infectious disease hospitalization
(subhazard ratio = 0.39; 95% CI, 0.24-0.64), as was time-updated nutrition status
(subhazard ratio = 0.73; 95% CI, 0.61-0.89). Incidence of infectious disease
hospitalization among formula-fed infants was 51/100 infant-years (95% CI, 37-70)
compared to 19/100 infant-years (95% CI, 14-25) among breastfed infants.
CONCLUSION: Among HEU infants, breastfeeding and nutrition status were associated
with reduced hospitalization during the first year of life.
PMID- 26423515
TI - Efficient experimental design for uncertainty reduction in gene regulatory
networks.
AB - BACKGROUND: An accurate understanding of interactions among genes plays a major
role in developing therapeutic intervention methods. Gene regulatory networks
often contain a significant amount of uncertainty. The process of prioritizing
biological experiments to reduce the uncertainty of gene regulatory networks is
called experimental design. Under such a strategy, the experiments with high
priority are suggested to be conducted first. RESULTS: The authors have already
proposed an optimal experimental design method based upon the objective for
modeling gene regulatory networks, such as deriving therapeutic interventions.
The experimental design method utilizes the concept of mean objective cost of
uncertainty (MOCU). MOCU quantifies the expected increase of cost resulting from
uncertainty. The optimal experiment to be conducted first is the one which leads
to the minimum expected remaining MOCU subsequent to the experiment. In the
process, one must find the optimal intervention for every gene regulatory network
compatible with the prior knowledge, which can be prohibitively expensive when
the size of the network is large. In this paper, we propose a computationally
efficient experimental design method. This method incorporates a network
reduction scheme by introducing a novel cost function that takes into account the
disruption in the ranking of potential experiments. We then estimate the
approximate expected remaining MOCU at a lower computational cost using the
reduced networks. CONCLUSIONS: Simulation results based on synthetic and real
gene regulatory networks show that the proposed approximate method has close
performance to that of the optimal method but at lower computational cost. The
proposed approximate method also outperforms the random selection policy
significantly. A MATLAB software implementing the proposed experimental design
method is available at
http://gsp.tamu.edu/Publications/supplementary/roozbeh15a/.
PMID- 26423517
TI - Numerical study of achiral phase-change metamaterials for ultrafast tuning of
giant circular conversion dichroism.
AB - Control of the polarization of light is highly desirable for detection of
material's chirality since biomolecules have vibrational modes in the optical
region. Here, we report an ultrafast tuning of pronounced circular conversion
dichroism (CCD) in the mid-infrared (M-IR) region, using an achiral phase change
metamaterial (PCMM). Our structure consists of an array of Au squares separated
from a continuous Au film by a phase change material (Ge2Sb2Te5) dielectric
layer, where the Au square patches occupy the sites of a rectangular lattice. The
extrinsically giant 2D chirality appears provided that the rectangular array of
the Au squares is illuminated at an oblique incidence, and accomplishes a wide
tunable wavelength range between 2664 and 3912 nm in the M-IR regime by switching
between the amorphous and crystalline states of the Ge2Sb2Te5. A photothermal
model is investigated to study the temporal variation of the temperature of the
Ge2Sb2Te5 layer, and shows the advantage of fast transiting the phase of
Ge2Sb2Te5 of 3.2 ns under an ultralow incident light intensity of 1.9 MUW/MUm(2).
Our design is straightforward to fabricate and will be a promising candidate for
controlling electromagnetic (EM) wave in the optical region.
PMID- 26423516
TI - A deuterostome origin of the Spemann organiser suggested by Nodal and ADMPs
functions in Echinoderms.
AB - During development of chordates, establishment of the body plan relies on the
activity of an organizing centre located on the dorsal side of the embryo that
patterns the embryo and induces neural tissue. Intriguingly, the evolutionary
origin of this crucial signalling centre remains unclear and whether analogous
organizers regulate D/V patterning in other deuterostome or protostome phyla is
not known. Here we provide evidence that the ventral ectoderm of the sea urchin
embryo is a long-range organizing centre that shares several fundamental
properties with the Spemann organizer: the ability to induce duplicated embryonic
axes when ectopically induced, the ability to induce neural fate in neighbouring
tissues and the ability to finely regulate the level of BMP signalling by using
an autoregulatory expansion-repression mechanism. These findings suggest that the
evolutionary origin of the Spemann organizer is more ancient than previously
thought and that it may possibly be traced back to the common ancestor of
deuterostomes.
PMID- 26423518
TI - Pri-miR-124 rs531564 polymorphism and colorectal cancer risk.
AB - MiR-124 functions as a tumor suppressor and plays an important role in
tumorigenesis. A common polymorphism (rs531564, C>G) in the pri-miR-124 has been
recently studied in connection with cancer risk. The aim of the present study was
to investigate the association between pri-miR-124 rs531564 polymorphism and the
risk and clinicopathological characteristics of colorectal cancer (CRC). Two case
control studies involving 900 CRC patients and 1110 cancer-free controls showed
that pri-miR-124 rs531564 polymorphism was significantly associated with the
decreased risk of CRC in Xuzhou population [GG vs. CC: OR = 0.25, 95%CI = 0.09
0.67, P = 0.003; (CG+GG) vs. CC: OR = 0.73, 95%CI = 0.56-0.94, P = 0.01; GG vs.
(CC+CG): OR = 0.27, 95%CI = 0.10-0.70, P = 0.004; G vs. C: OR = 0.70, 95%CI =
0.56-0.89, P = 0.003], Bengbu population [GG vs. CC: OR = 0.20, 95%CI = 0.04
0.90, P = 0.02; GG vs. (CC+CG): OR = 0.21, 95%CI = 0.05-0.95, P = 0.03; G vs. C:
OR = 0.72, 95%CI = 0.54-0.98, P = 0.03] and pooled population [GG vs. CC: OR =
0.26, 95%CI = 0.11-0.59, P<0.001; (CG+GG) vs. CC: OR = 0.76, 95%CI = 0.62-0.93, P
= 0.008; GG vs. (CC+CG): OR = 0.27, 95%CI = 0.12-0.62, P < 0.001; G vs. C: OR =
0.71, 95%CI = 0.59-0.85, P<0.001]. Additionally, pri-miR-124 rs531564
polymorphism was significantly associated with the decreased risk of poor
differentiation and lymph node metastasis of CRC. Our results suggest that pri
miR-124 rs531564 polymorphism may be a genetic modifier for developing CRC.
However, further studies are needed to validate our findings.
PMID- 26423519
TI - Origin of Self-preservation Effect for Hydrate Decomposition: Coupling of Mass
and Heat Transfer Resistances.
AB - Gas hydrates could show an unexpected high stability at conditions out of
thermodynamic equilibrium, which is called the self-preservation effect. The
mechanism of the effect for methane hydrates is here investigated via molecular
dynamics simulations, in which an NVT/E method is introduced to represent
different levels of heat transfer resistance. Our simulations suggest a coupling
between the mass transfer resistance and heat transfer resistance as the driving
mechanism for self-preservation effect. We found that the hydrate is initially
melted from the interface, and then a solid-like water layer with temperature
dependent structures is formed next to the hydrate interface that exhibits
fractal feature, followed by an increase of mass transfer resistance for the
diffusion of methane from hydrate region. Furthermore, our results indicate that
heat transfer resistance is a more fundamental factor, since it facilitates the
formation of the solid-like layer and hence inhibits the further dissociation of
the hydrates. The self-preservation effect is found to be enhanced with the
increase of pressure and particularly the decrease of temperature. Kinetic
equations based on heat balance calculations is also developed to describe the
self-preservation effect, which reproduces our simulation results well and
provides an association between microscopic and macroscopic properties.
PMID- 26423521
TI - In Memoriam: Alexander V. Nichols (1924 - 2015).
PMID- 26423520
TI - Simplified assays of lipolysis enzymes for drug discovery and specificity
assessment of known inhibitors.
AB - Lipids are used as cellular building blocks and condensed energy stores and also
act as signaling molecules. The glycerolipid/ fatty acid cycle, encompassing
lipolysis and lipogenesis, generates many lipid signals. Reliable procedures are
not available for measuring activities of several lipolytic enzymes for the
purposes of drug screening, and this resulted in questionable selectivity of
various known lipase inhibitors. We now describe simple assays for lipolytic
enzymes, including adipose triglyceride lipase (ATGL), hormone sensitive lipase
(HSL), sn-1-diacylglycerol lipase (DAGL), monoacylglycerol lipase, alpha/beta
hydrolase domain 6, and carboxylesterase 1 (CES1) using recombinant human and
mouse enzymes either in cell extracts or using purified enzymes. We observed that
many of the reported inhibitors lack specificity. Thus, Cay10499 (HSL inhibitor)
and RHC20867 (DAGL inhibitor) also inhibit other lipases. Marked differences in
the inhibitor sensitivities of human ATGL and HSL compared with the corresponding
mouse enzymes was noticed. Thus, ATGListatin inhibited mouse ATGL but not human
ATGL, and the HSL inhibitors WWL11 and Compound 13f were effective against mouse
enzyme but much less potent against human enzyme. Many of these lipase inhibitors
also inhibited human CES1. Results describe reliable assays for measuring lipase
activities that are amenable for drug screening and also caution about the
specificity of the many earlier described lipase inhibitors.
PMID- 26423522
TI - A single-nucleotide-polymorphism real-time PCR assay for genotyping of
Mycobacterium tuberculosis complex in peri-urban Kampala.
AB - BACKGROUND: Accurate and high-throughput genotyping of Mycobacterium tuberculosis
complex (MTBC) may be important for understanding the epidemiology and
pathogenesis of tuberculosis (TB). In this study, we report the development of a
LightCycler(r) real-time PCR single-nucleotide-polymorphism (LRPS) assay for the
rapid determination of MTBC lineages/sublineages in minimally processed sputum
samples from TB patients. METHOD: Genotyping analysis of 70 MTBC strains was
performed using the Long Sequence Polymorphism-PCR (LSP-PCR) technique and the
LRPS assay in parallel. For targeted sequencing, 9 MTBC isolates (three isolates
per MTBC lineage) were analyzed for lineage-specific single nucleotide
polymorphisms (SNPs) in the following three genes to verify LRPS results: Rv004c
for MTB Uganda family, Rv2962 for MTB lineage 4, and Rv0129c for MTB lineage 3.
The MTBC lineages present in 300 smear-positive sputum samples were then
determined by the validated LRPS method without prior culturing. RESULTS: The LSP
PCR and LRPS assays produced consistent genotyping data for all 70 MTBC strains;
however, the LSP-PCR assay was 10-fold less sensitive than the LRPS method and
required higher DNA concentrations to successfully characterize the MTBC lineage
of certain samples. Targeted sequencing of genes containing lineage-specific SNPs
was 100 % concordant with the genotyping results and provided further validation
of the LRPS assay. Of the 300 sputum samples analyzed, 58 % contained MTBC from
the MTBC-Uganda family, 27 % from the MTBC lineage 4 (excluding MTBC Uganda
family), 13 % from the MTBC lineage 3, and the remaining 2 % were of
indeterminate lineage. CONCLUSION: The LRPS assay is a sensitive, high-throughput
technique with potential application to routine genotyping of MTBC in sputum
samples from TB patients.
PMID- 26423523
TI - Associations between biosecurity and outbreaks of canine distemper on Danish mink
farms in 2012-2013.
AB - BACKGROUND: During 8 months from July 2012 to February 2013, a major outbreak of
canine distemper involving 64 mink farms occurred on the Danish peninsula of
Jutland. The canine distemper outbreak was associated with exposure of farmed
mink to infected wild carnivores and could represent a deficit in biosecurity on
the mink farms. The aim of this study was to investigate the extent and
association of specific biosecurity measures with the outbreak. The study was
carried out in an epidemiological case-control design. The case group consisted
of the 61 farms, which had a confirmed outbreak of canine distemper from July
2012 to February 2013. The control group included 54 farms without an outbreak of
canine distemper in 2012 or 2013, selected as the closest geographical neighbour
to a case farm. RESULTS: The results showed that significantly more control than
case farms had vaccinated their mink against canine distemper virus. Mortality
was only assessed on the case farms, and there was a non-significantly lower
mortality on vaccinated farms than on the non-vaccinated farms. Furthermore, the
proportion of farms with observations of wild red foxes (Vulpes vulpes) inside
the farm enclosures were larger for case farms, indicating that the control farms
had a better biosecurity or were not equally exposed to canine distemper virus.
Generally, all farms had very few specific precautions at the gate entrance in
respect to human visitors as well as animals. The use of biosecurity measures was
very variable in both case and control farms. Not using plastic boot covers,
presence of dogs and cats, presence of demarcated area for changing clothes when
entering and leaving the farm area and presence of hand washing facilities
significantly lowered the odds of the farm having a canine distemper virus
outbreak. CONCLUSIONS: The results of the study indicate that consistent use of
correct vaccination strategies, implementation of biosecurity measures and
limiting human and animal access to the mink farm can be important factors in
reducing the risk for canine distemper outbreaks.
PMID- 26423524
TI - Aerobic and strength exercises for youngsters aged 12 to 15: what do parents
think?
AB - BACKGROUND: Although strength exercises evidently have both physiological and
psychological health benefits across all ages, they are erroneously considered to
adversely affect health status in youngsters. The aim of this study was to
examine parental attitudes towards their child's physical activity in general, as
well as aerobic and strength exercises in particular. METHODS: In total, 314
parents from an online panel representative of the Dutch population completed an
online survey about their own physical activity and that of their child (12-15
years old). The study also explored reasons for non-participation, and attitudes
about the parents' own and their child's physical activity level. RESULTS:
Parents consistently reported a positive attitude towards aerobic exercises, but
a less positive attitude regarding strength exercises. Parents were more likely
to indicate that their child was not allowed to participate in strength exercises
(29.6 %) than aerobic exercises (4.0 %). They thought that strength exercises
could interfere with optimal physical development. CONCLUSIONS: This study
consistently shows that parents have a positive attitude towards aerobic
exercises, but a less positive attitude regarding strength exercises. We suggest
testing interventions to increase parental understanding of the advantages of and
possibilities for (e.g., facilities) strength training on their child's health.
PMID- 26423525
TI - Evaluation of wound healing and anti-inflammatory activity of the rhizomes of
Rumex abyssinicus J. (Polygonaceae) in mice.
AB - BACKGROUND: Rumex abyssinicus Jacq (Polygonaceae) is widely used in Ethiopia for
treatment of wound and other diseases. Although reports are available in the
literature on some of the claimed activities, nothing has so far been reported
about the wound healing activity of R. abyssinicus. Thus, this work was initiated
to investigate the wound healing and anti-inflammatory activities of 80% methanol
extract of the rhizomes of R. abyssinicus in mice. METHODS: Following extraction
of the rhizomes of the plant with 80% methanol, the extract was formulated as
ointment (5% & 10% w/w) with simple ointment base B.P. The ointment was then
evaluated for wound healing activity using excision and incision wound models.
Parameters, including wound contraction, epithelization time and hydroxyproline
content were determined using the excision model, whereas tensile strength was
measured from the incision model. In parallel, anti-inflammatory activity of the
rhizome was evaluated with carrageenan induced hind paw edema model by dissolving
the 80% methanol extract in 1% carboxyl methyl cellulose and administering orally
in various doses (250, 500 and 750 mg/kg). RESULTS: Wound treated with 5% and 10%
(w/w) hydroalcoholic extract ointment exhibited significant wound healing
activity in both models, as evidenced by increased wound contraction, shorter
epithelization time, higher tissue breaking strength and increased hydroxyproline
content. The hydroalcoholic extract also produced dose-related significant
reduction (p < 0.05-0.001) of inflammation. CONCLUSIONS: The results of this
study demonstrated that the hydroalcoholic extract of the rhizomes of R.
abyssinicus facilitated wound healing at least in part via its anti-inflammatory
activity, supporting its traditional claim as a wound healing agent.
PMID- 26423526
TI - "Borderline" fluorotic region in Serbia: correlations among fluoride in drinking
water, biomarkers of exposure and dental fluorosis in schoolchildren.
AB - This study explores relation between dental fluorosis occurrence in
schoolchildren, residents of Ritopek, a small local community near Belgrade, and
fluoride exposure via drinking water. Additionally, fluoride levels were
determined in children's urine and hair samples, and efforts were made to
correlate them with dental fluorosis. Dental fluorosis and caries prevalence were
examined in a total of 52 schoolchildren aged 7-15 years (29 boys and 23 girls).
Fluoride levels in three types of samples were analyzed using composite fluoride
ion-selective electrode. Results showed high prevalence of dental fluorosis (34.6
%) and low prevalence of dental caries (23.1 %, mean DMFT 0.96) among children
exposed to wide range of water fluoride levels (0.11-4.14 mg/L, n = 27). About 11
% of water samples exceeded 1.5 mg/L, a drinking-water quality guideline value
for fluoride given by the World Health Organization (2006). Fluoride levels in
urine and hair samples ranged between 0.07-2.59 (n = 48) and 1.07-19.83 mg/L (n =
33), respectively. Severity of dental fluorosis was positively and linearly
correlated with fluoride levels in drinking water (r = 0.79). Fluoride levels in
urine and hair were strongly and positively correlated with levels in drinking
water (r = 0.92 and 0.94, respectively). Fluoride levels in hair samples appeared
to be a potentially promising biomarker of fluoride intake via drinking water on
one hand, and severity of dental fluorosis on the other hand. Based on community
fluorosis index value of 0.58, dental fluorosis revealed in Ritopek can be
considered as "borderline" public health issue.
PMID- 26423527
TI - Assessment of indoor heat stress variability in summer and during heat warnings:
a case study using the UTCI in Berlin, Germany.
AB - Humans spend most of their time in confined spaces and are hence primarily
exposed to the direct influence of indoor climate. The Universal Thermal Climate
Index (UTCI) was obtained in 31 rooms (eight buildings) in Berlin, Germany,
during summer 2013 and 2014. The indoor UTCI was determined from measurements of
both air temperature and relative humidity and from data of mean radiant
temperature and air velocity, which were either measured or modeled. The
associated outdoor UTCI was obtained through facade measurements of air
temperature and relative humidity, simulation of mean radiant temperature, and
wind data from a central weather station. The results show that all rooms
experienced heat stress according to UTCI levels, especially during heat waves.
Indoor UTCI varied up to 6.6 K within the city and up to 7 K within building.
Heat stress either during day or at night occurred on 35 % of all days. By
comparing the day and night thermal loads, we identified maximum values above the
32 degrees C threshold for strong heat stress during the nighttime. Outdoor UTCI
based on facade measurements provided no better explanation of indoor UTCI
variability than the central weather station. In contrast, we found a stronger
relationship of outdoor air temperature and indoor air temperature. Building
characteristics, such as the floor level or window area, influenced indoor heat
stress ambiguously. We conclude that indoor heat stress is a major hazard, and
more effort toward understanding the causes and creating effective
countermeasures is needed.
PMID- 26423528
TI - Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive
behavior and striatal activation.
AB - RATIONALE: Serotonin-1B receptor (5-HT1BR) agonist treatment induces obsessive
compulsive disorder (OCD)-like behaviors including locomotor stereotypy, prepulse
inhibition deficits, and delayed alternation disruptions, which are selectively
prevented by clinically effective OCD treatment. However, the role of 5-HT1BRs in
modulating other repetitive behaviors or OCD-like patterns of brain activation
remains unclear. OBJECTIVES: We assessed the effects of 5-HT1BR agonism on
digging, grooming, and open field behaviors in mice. We also quantified effects
on neuronal activation in brain regions overactivated in OCD. Finally, we
assessed whether effects of the 5-HT1BR challenge could be blocked by clinically
effective, but not ineffective, drug treatments. METHODS: Mice were tested in
open field, dig, and splash tests after acute treatment with saline, 1, 3, 5, or
10 mg/kg RU24969 (5-HT1B/1A agonist). Behavioral effects of RU24969 were also
tested following co-treatment with vehicle, 1 mg/kg WAY100635 (5-HT1A antagonist)
and 5 or 10 mg/kg GR127935 (5HT1B/D antagonist). Separate mice were behaviorally
assessed following chronic pretreatment with vehicle with 10 mg/kg fluoxetine or
20 mg/kg desipramine and acute treatment with saline or 10 mg/kg RU24969. Brains
were analyzed for Fos expression in the orbitofrontal cortex, the dorsal
striatum, and the cerebellum. RESULTS: RU24969 induced robust locomotor
stereotypy and decreased rearing, digging, and grooming. Effects were blocked by
GR127935 but not by WAY100635. RU24969 also increased Fos expression in the
dorsal striatum. Chronic fluoxetine, but not desipramine, alleviated 5-HT1BR
induced effects. CONCLUSIONS: We report novel 5-HT1BR-induced behaviors and
striatal activation that were alleviated only by clinically effective
pharmacological OCD treatment. Studying the mechanisms underlying these effects
could provide insight into OCD pathophysiology.
PMID- 26423529
TI - Exercise for Hypertension: A Prescription Update Integrating Existing
Recommendations with Emerging Research.
AB - Hypertension is the most common, costly, and preventable cardiovascular disease
risk factor. Numerous professional organizations and committees recommend
exercise as initial lifestyle therapy to prevent, treat, and control
hypertension. Yet, these recommendations differ in the components of the
Frequency, Intensity, Time, and Type (FITT) principle of exercise prescription
(Ex Rx); the evidence upon which they are based is only of fair methodological
quality; and the individual studies upon which they are based generally do not
include people with hypertension, which are some of the limitations in this
literature. The purposes of this review are to (1) overview the professional
exercise recommendations for hypertension in terms of the FITT principle of Ex
Rx; (2) discuss new and emerging research related to Ex Rx for hypertension; and
(3) present an updated FITT Ex Rx for adults with hypertension that integrates
the existing recommendations with this new and emerging research.
PMID- 26423530
TI - RAP1-GTPase signaling and platelet function.
AB - Platelets are critical for hemostasis, i.e., the body's ability to prevent blood
loss at sites of vascular injury. They patrol the vasculature in a quiescent, non
adhesive state for approximately 10 days, after which they are removed from
circulation by phagocytic cells of the reticulo-endothelial system. At sites of
vascular injury, they promptly shift to an activated, adhesive state required for
the formation of a hemostatic plug. The small GTPase RAP1 is a critical regulator
of platelet adhesiveness. Our recent studies demonstrate that the antagonistic
balance between the RAP1 regulators, CalDAG-GEFI and RASA3, is critical for the
modulation of platelet adhesiveness, both in circulation and at sites of vascular
injury. The RAP1 activator CalDAG-GEFI responds to small changes in the
cytoplasmic calcium concentration and thus provides sensitivity and speed to the
activation response, essential for efficient platelet adhesion under conditions
of hemodynamic shear stress. The RAP1 inhibitor RASA3 ensures that circulating
platelets remain quiescent by restraining CalDAG-GEFI-dependent RAP1 activation.
Upon cellular stimulation, it is turned off by P2Y12 signaling to enable
sustained RAP1 activation, required for the formation of a stable hemostatic
plug. This review will summarize important studies that elucidated the signaling
pathways that control RAP1 activation in platelets.
PMID- 26423532
TI - Familial inflammatory bowel diseases in Northwest Greece.
PMID- 26423533
TI - Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human
cells.
AB - Human Immunodeficiency Virus type 1 (HIV-1) major structure protein Gag is
synthesized in the cytoplasm, assembles on the plasma membrane, subsequently buds
and releases. HIV-1 viral particles incorporate a number of host proteins to
facilitate or inhibit HIV-1 replication. Here we identify a new host protein,
coiled-coil domain containing protein 8 (CCDC8), in HIV-1 particles.
Incorporation of CCDC8 into virions is dependent on the interaction between CCDC8
and Gag matrix region. Exogenous overexpression of CCDC8 can strongly inhibit HIV
1 production, up to ~30 fold. CCDC8 is a membrane-associated protein. The
interaction between exogenously expressed CCDC8 and Gag on the plasma membrane
changes the assembly of Gag, and redirects it into intracellular sites, or causes
Gag endocytosis. CCDC8, along with cytoskeleton protein obscuring-like1 (Obsl1)
and E3 ligase Cul7, induces Gag polyubiquitination and degradation. Thus we
identify a new host protein and a new pathway for HIV-1 Gag polyubiquitination
and degradation. This pathway presents potential therapeutic strategies against
HIV infection.
PMID- 26423534
TI - Typical evanescent and atypical persistent polymorphic cutaneous rash in an adult
Brazilian with Still's disease: a case report and review of the literature.
AB - Adult onset Still's disease (AOSD) is a systemic auto-inflammatory condition of
unknown etiology, characterized by high fever, an evanescent, salmon-pink
maculopapular skin rash, arthralgia or arthritis and leukocytosis. AOSD can also
present with atypical cutaneous manifestations, such as persistent pruritic
coalescent papules or plaques and linear lesions that have highly distinctive
pathological features and are usually associated with severe disease. Herein, we
present a 31-year-old Brazilian man with both typical Still's rash and atypical
persistent polymorphic cutaneous manifestations associated with severe systemic
inflammatory response syndrome. Eosinophils that are consistently lacking in the
AOSD-associated skin lesions were evident in the skin biopsy of the persistent
atypical cutaneous manifestations and were either drug-related or AOSD
associated.
PMID- 26423535
TI - HLA-genotyping of clinical specimens using Ion Torrent-based NGS.
AB - We have evaluated and validated the NXTypeTM workflow (One Lambda, Inc.) and the
accompanying TypeStreamTM software on the Ion Torrent Next Generation Sequencing
(NGS) platform using a comprehensive testing panel. The panel consisted of 285
genomic DNA (gDNA) samples derived from four major ethnic populations and
contained 59 PT samples and 226 clinical specimens. The total number of alleles
from the six loci interrogated by NGS was 3420. This validation panel provided a
wide range of HLA sequence variations including many rare alleles, new variants
and homozygous alleles. The NXTypeTM system (reagents and software) was able to
correctly genotype the vast majority of these specimens. The concordance rate
between SBT-derived genotypes and those generated by TypeStreamTM auto-analysis
ranged from 99.5% to 99.8% for the HLA-A, B, C, DRB1 and DQB1 loci, and was 98.9%
for HLA-DPB1. A strategy for data review was developed that would allow
correction of most of the few remaining typing errors. The entire NGS workflow
from gDNA amplification to genotype assignment could be completed within 3
working days. Through this validation study, the limitations and shortcomings of
the platform, specific assay system, and software algorithm were also revealed
for further evaluation and improvement.
PMID- 26423531
TI - Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic
opportunities.
AB - Multiple myeloma is a plasma cell skeletal malignancy. While therapeutic agents
such as bortezomib and lenalidomide have significantly improved overall survival,
the disease is currently incurable with the emergence of drug resistance limiting
the efficacy of chemotherapeutic strategies. Failure to cure the disease is in
part due to the underlying genetic heterogeneity of the cancer. Myeloma
progression is critically dependent on the surrounding microenvironment. Defining
the interactions between myeloma cells and the more genetically stable
hematopoietic and mesenchymal components of the bone microenvironment is critical
for the development of new therapeutic targets. In this review, we discuss recent
advances in our understanding of how microenvironmental elements contribute to
myeloma progression and, therapeutically, how those elements can or are currently
being targeted in a bid to eradicate the disease.
PMID- 26423536
TI - Advances in DNA sequencing technologies for high resolution HLA typing.
AB - This communication describes our experience in large-scale G group-level high
resolution HLA typing using three different DNA sequencing platforms - ABI 3730
xl, Illumina MiSeq and PacBio RS II. Recent advances in DNA sequencing
technologies, so-called next generation sequencing (NGS), have brought
breakthroughs in deciphering the genetic information in all living species at a
large scale and at an affordable level. The NGS DNA indexing system allows
sequencing multiple genes for large number of individuals in a single run. Our
laboratory has adopted and used these technologies for HLA molecular testing
services. We found that each sequencing technology has its own strengths and
weaknesses, and their sequencing performances complement each other. HLA genes
are highly complex and genotyping them is quite challenging. Using these three
sequencing platforms, we were able to meet all requirements for G group-level
high resolution and high volume HLA typing.
PMID- 26423538
TI - How achievable is immediate ART for all?
PMID- 26423539
TI - Mortality risk in older people on antiretroviral therapy.
PMID- 26423537
TI - Infections, inflammation and epilepsy.
AB - Epilepsy is the tendency to have unprovoked epileptic seizures. Anything causing
structural or functional derangement of brain physiology may lead to seizures,
and different conditions may express themselves solely by recurrent seizures and
thus be labelled "epilepsy." Worldwide, epilepsy is the most common serious
neurological condition. The range of risk factors for the development of epilepsy
varies with age and geographic location. Congenital, developmental and genetic
conditions are mostly associated with the development of epilepsy in childhood,
adolescence and early adulthood. Head trauma, infections of the central nervous
system (CNS) and tumours may occur at any age and may lead to the development of
epilepsy. Infections of the CNS are a major risk factor for epilepsy. The
reported risk of unprovoked seizures in population-based cohorts of survivors of
CNS infections from developed countries is between 6.8 and 8.3 %, and is much
higher in resource-poor countries. In this review, the various viral, bacterial,
fungal and parasitic infectious diseases of the CNS which result in seizures and
epilepsy are discussed. The pathogenesis of epilepsy due to brain infections, as
well as the role of experimental models to study mechanisms of epileptogenesis
induced by infectious agents, is reviewed. The sterile (non-infectious)
inflammatory response that occurs following brain insults is also discussed, as
well as its overlap with inflammation due to infections, and the potential role
in epileptogenesis. Furthermore, autoimmune encephalitis as a cause of seizures
is reviewed. Potential strategies to prevent epilepsy resulting from brain
infections and non-infectious inflammation are also considered.
PMID- 26423540
TI - Does early ART in sub-Saharan Africa decrease mortality?
PMID- 26423541
TI - Antiretroviral therapy and perinatal outcomes.
PMID- 26423542
TI - Making the economic case for universal ART access.
PMID- 26423543
TI - Addressing barriers to the end of AIDS by 2030.
PMID- 26423544
TI - Ensuring new medicines reach those in most need.
PMID- 26423545
TI - Interpretation, communication, and mechanisms of associations between injectable
contraception and HIV risk.
PMID- 26423546
TI - Interpretation, communication, and mechanisms of associations between injectable
contraception and HIV risk.
PMID- 26423547
TI - Interpretation, communication, and mechanisms of associations between injectable
contraception and HIV risk - Authors' reply.
PMID- 26423548
TI - Interpretation, communication, and mechanisms of associations between injectable
contraception and HIV risk.
PMID- 26423549
TI - Interpretation, communication, and mechanisms of associations between injectable
contraception and HIV risk - Authors' reply.
PMID- 26423550
TI - Age in antiretroviral therapy programmes in South Africa: a retrospective,
multicentre, observational cohort study.
AB - BACKGROUND: As access to antiretroviral therapy (ART) expands, increasing numbers
of older patients will start treatment and need specialised long-term care.
However, the effect of age in ART programmes in resource-constrained settings is
poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of
the highest HIV population prevalences worldwide. We explored the effect of age
on mortality of patients on ART in South Africa and whether this effect is
mediated by baseline immunological status. METHODS: In this retrospective cohort
analysis, we studied HIV-positive patients aged 16-80 years who started ART for
the first time in six large South African cohorts of the International
Epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, in
KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three
hospitals, and a large rural cohort). The primary outcome was mortality. We
ascertained patients' vital status through linkage to the National Population
Register. We used inverse probability weighting to correct mortality for loss to
follow-up. We estimated mortality using Cox's proportional hazards and competing
risks regression. We tested the interaction between baseline CD4 cell count and
age. FINDINGS: Between Jan 1, 2004, and Dec 31, 2013, 84,078 eligible adults
started ART. Of these, we followed up 83,566 patients for 174,640 patient-years.
8% (1817 of 23,258) of patients aged 16-29 years died compared with 19% (93 of
492) of patients aged 65 years or older. The age adjusted mortality hazard ratio
was 2.52 (95% CI 2.01-3.17) for people aged 65 years or older compared with those
16-29 years of age. In patients starting ART with a CD4 count of less than 50
cells per MUL, the adjusted mortality hazard ratio was 2.52 (2.04-3.11) for
people aged 50 years or older compared with those 16-39 years old. Mortality was
highest in patients with CD4 counts of less than 50 cells per MUL, and 15% (1103
of 7295) of all patients aged 50 years or older starting ART were in this group.
The proportion of patients aged 50 years or older enrolling in ART increased with
successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13,
comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304
(14%) of 44,909 patients still alive and in care were aged 50 years or older.
INTERPRETATION: Health services need reorientation towards HIV diagnosis and
starting of ART in older individuals. Policies are needed for long-term care of
older people with HIV. FUNDING: National Institutes of Health (National Institute
of Allergy and Infectious Diseases), US Agency for International Development, and
South African Centre for Epidemiological Modelling and Analysis.
PMID- 26423551
TI - Effect of baseline CD4 cell count at linkage to HIV care and at initiation of
antiretroviral therapy on mortality in HIV-positive adult patients in Rwanda: a
nationwide cohort study.
AB - BACKGROUND: Continued debate exists about whether initiation of antiretroviral
therapy (ART) in symptom-free patients at higher baseline CD4 cell counts results
in important clinical benefits. We aimed to examine to what extent baseline CD4
cell count at linkage to HIV care and at ART initiation predicts mortality in
adults with HIV in Rwanda. METHODS: We included data for patients with HIV in
Rwanda who were aged 15 years or older and linked to care or initiated ART
between Jan 1, 1997, and April 30, 2014, from nationally representative
databases. We analysed the effect on mortality of baseline CD4 cell count at ART
initiation and at linkage to care. Follow-up time was measured from time of ART
initiation and from linkage to HIV care to study exit. To account for effect
modification by time, we stratified by era of linkage (before 2008 vs 2008 or
after) and for other indications for initiation of ART. We also stratified CD4
cell count by indication to initiate ART other than CD4 cell count status. We
used Cox proportional hazard regressions to examine the effect of CD4 cell count
at linkage and at ART initiation on mortality. FINDINGS: Our analysis was based
on data from 50,147 patients who initiated ART and 72,061 patients linked to
care. In the late era (2008 and after), linkage to care at a CD4 cell count of
100-199 cells per MUL without any further indication was associated with higher
mortality than linkage at 200-349 cells per MUL (hazard ratio [HR] 1.37, 95% CI
0.95-1.97); the effect was much the same for initiation of ART in this CD4
stratum (1.37, 0.92-2.04). For higher CD4 strata, linkage to care at 500 cells
per MUL or more was protective (0.53, 0.39-0.72), whereas the reported effect of
initiation of ART on mortality was not distinguishable from chance alone (0.82,
0.21-3.20). INTERPRETATION: Efforts are needed to link and retain patients early
in pre-ART HIV care. In settings where ART is not yet available for immediate
treatment, retention in a strong pre-ART programme is effective at improving
survival. FUNDING: The Bill & Melinda Gates Foundation.
PMID- 26423552
TI - Pregnancy outcomes in HIV-positive women in Ukraine, 2000-12 (European
Collaborative Study in EuroCoord): an observational cohort study.
AB - BACKGROUND: Women living with HIV are potentially at increased risk of adverse
pregnancy outcomes, due to a range of factors, including immunosuppression, use
of combination antiretroviral therapy (ART), and injecting drug use. Rates of
mother-to-child transmission of HIV in Ukraine have declined to around 2-4%, but
little is known about other pregnancy outcomes in this setting. We used data from
an observational prospective cohort study to assess pregnancy outcomes among HIV
positive women in Ukraine. METHODS: The European Collaborative Study (ECS) in
EuroCoord is a continuing cohort study, established in Ukraine in 2000. Eligible
women are those with a diagnosis of HIV infection before or during pregnancy
(including intrapartum) who deliver liveborn babies at seven sites. Maternal
sociodemographic, HIV-related, and delivery (mother and infant) data were
collected with study-specific questionnaires. We used Poisson regression models
to identify factors associated with preterm delivery (before 37 weeks' gestation)
and small weight for gestational age (less than the tenth percentile of weight
for gestational age), based on complete cases. FINDINGS: Between January, 2000,
and July, 2012, data were collected on 8884 HIV-positive mother and liveborn
infant pairs. Median maternal age was 26.5 years (IQR 23.1-30.3). 832 (11%) women
had WHO stage 3 or 4 HIV and 1474 (17%) had a history of injecting drug use. 7348
(83%) had received antenatal ART. Among 7435 for whom ART type was available,
4396 (50%) had received zidovudine monotherapy and 2949 (33%) combination ART.
Preterm delivery was seen in 780 (9%, 95% CI 8-9) of 8860 births overall and in
77 (9%, 7-11) of 889 babies with small size for gestational age. Factors
associated with preterm delivery were history of injecting drug use (adjusted
risk ratio 1.64, 95% CI 1.38-1.95), no ART (2.94, 2.43-3.57 vs zidovudine
monotherapy), antenatal combination ART (1.40, 1.14-1.73 vs zidovudine
monotherapy), WHO stage 4 HIV (2.42, 1.71-3.41 vs WHO stage 1), and being in the
most socially deprived group (1.38, 1.11-1.71). Small size for gestational age
was associated with history of injecting drug use (adjusted RR 1.39, 95% CI 1.16
1.65), most socially deprived (1.32, 1.09-1.61), no ART (1.60, 1.32-1.94 vs
zidovudine monotherapy), and antenatal combination ART (1.33, 1.12-1.60 vs
zidovudine monotherapy). INTERPRETATION: Some risk factors for adverse pregnancy
outcomes were directly associated with HIV and treatment and others were shared
with the general antenatal population. Monitoring of pregnancy outcomes in
Ukraine will be important as use of antenatal combination ART increases. FUNDING:
European Union Seventh Framework Programme, Wellcome Trust.
PMID- 26423553
TI - Cost-effectiveness of population-level expansion of highly active antiretroviral
treatment for HIV in British Columbia, Canada: a modelling study.
AB - BACKGROUND: Widespread HIV screening and access to highly active antiretroviral
treatment (ART) were cost effective in mathematical models, but population-level
implementation has led to questions about cost, value, and feasibility. In 1996,
British Columbia, Canada, introduced universal coverage of drug and other health
care costs for people with HIV/AIDS and and began extensive scale-up in access to
ART. We aimed to assess the cost-effectiveness of ART scale-up in British
Columbia compared with hypothetical scenarios of constrained treatment access.
METHODS: Using comprehensive linked population-level data, we populated a
dynamic, compartmental transmission model to simulate the HIV/AIDS epidemic in
British Columbia from 1997 to 2010. We estimated HIV incidence, prevalence,
mortality, costs (in 2010 CAN$), and quality-adjusted life-years (QALYs) for the
study period, which was 1997-2010. We calculated incremental cost-effectiveness
ratios from societal and third-party-payer perspectives to compare actual
practice (true numbers of individuals accessing ART) to scenarios of constrained
expansion (75% and 50% probability of accessing ART). We also investigated
structural and parameter uncertainty. FINDINGS: Actual practice resulted in 263
averted incident cases compared with 75% of observed access and 676 averted cases
compared with 50% of observed access to ART. From a third-party-payer
perspective, actual practice resulted in incremental cost-effectiveness ratios of
$23 679 per QALY versus 75% access and $24 250 per QALY versus 50% access. From a
societal perspective, actual practice was cost saving within the study period.
When the model was extended to 2035, current observed access resulted in
cumulative savings of $25.1 million compared with the 75% access scenario and
$65.5 million compared with the 50% access scenario. INTERPRETATION: ART scale-up
in British Columbia has decreased HIV-related morbidity, mortality, and
transmission. Resulting incremental cost-effectiveness ratios for actual
practice, derived within a limited timeframe, were within established cost
effectiveness thresholds and were cost saving from a societal perspective.
FUNDING: BC Ministry of Health, National Institute of Drug Abuse at the US
National Institutes of Health.
PMID- 26423554
TI - Campylobacter jejuni PflB is required for motility and colonisation of the
chicken gastrointestinal tract.
AB - Campylobacter jejuni is the leading cause of foodborne bacterial gastroenteritis
worldwide. Although the mechanisms by which C. jejuni causes disease are not
completely understood, the presence of functional flagella appears to be required
for colonisation of the gastrointestinal tract of humans and animals. Therefore
much attention has been given to understanding the synthesis and role of flagella
in C. jejuni. In this study we report insights into the function of PflB that is
essential for Campylobacter motility. We have explored the function of this gene
by constructing deletion mutants in C. jejuni strains NCTC11168 and M1, in the
genes cj0390 and CJM1_0368, respectively. The mutants were non-motile yet
assembled flagella that appeared structurally identical to the wild type.
Furthermore the protein is required for C. jejuni colonisation of caeca in a two
week old chicken colonisation model.
PMID- 26423555
TI - Identification of CD4+ T-cell epitopes on iron-regulated surface determinant B of
Staphylococcus aureus.
AB - Iron-regulated surface determinant B (IsdB) of Staphylococcus aureus (S. aureus)
is a highly conserved surface protein that can induce protective CD4(+) T-cell
immune response. A pivotal role of CD4(+) T-cells in effective immunity against
S. aureus infection has been proved, but CD4(+) T-cell epitopes on the S. aureus
IsdB have not been well identified. In this study, MHC binding assay was firstly
used to predict CD4(+) T-cell epitopes on S. aureus IsdB protein, and six
peptides were synthesized to validate the probable epitopes. Two novel IsdB
CD4(+) T-cell epitopes, P1 (residues 159-178) and P4 (residues 287-306), were for
the first time identified using CD4(+) T-cells obtained from IsdB-immunized
C57BL/6 (H-2(b)) and BALB/c (H-2(d)) mice spleen based on cell proliferation and
cytokines response. The results showed that P1 and P4 emulsified in Freund's
adjuvant (FA) induced much higher cell proliferation compared with PBS emulsified
in FA. CD4(+) T-cells stimulated with peptides P1 and P4 secreted significantly
higher levels of IFN-gamma and IL-17A. However, the level of the cytokine IL-4
almost remained unchanged, suggesting that P1 and P4 preferentially elicited
polarized Th1-type responses. In addition, BALB/c mice just respond to P4 not P1,
while C57BL/6 mice respond to P1 not P4, implying that epitope P1 and P4 were
determined as H-2(b) and H-2(d) restricted epitope, respectively. Taken together,
our data may provide an explanation of the IsdB-induced protection against S.
aureus and highlight the possibility of developing the epitope-based vaccine
against the S. aureus.
PMID- 26423556
TI - A 10 year survey of acaricide residues in beeswax analysed in Italy.
AB - BACKGROUND: The aim of this work was to provide an overview of the prevalence and
level of acaricides in beeswax used in Italy in the past 10 years by analysing
1319 beeswax samples processed by the certified laboratory of the Italian Bee
Research Institute. RESULTS: The proportion of samples positive to at least one
active ingredient decreased between 2005 and 2009 (from 69 to 32%) and then
increased again between 2009 and 2014 (from 32 to 91%). This trend is in
agreement with reports from beekeepers that the use of synthetic acaricides
decreased in the second half of the past decade and increased after the beginning
of the colony losses phenomenon. The active ingredient with the greatest overall
proportion of positive samples was coumaphos (49%), followed by fluvalinate (38%)
and chlorphenvinphos (25%). The indicator for amitraz, 2,4
dimethylphenylformamide (DMPF), was detected in a very small proportion of
samples (6%), while residues of cymiazole were never found. CONCLUSIONS: In more
than half of the analysed samples, residues of at least one active ingredient
were detected. The mean levels of residues of all the considered active
ingredients in the positive samples may represent a source of accumulation in
beeswax and pose risks to honey bee health. (c) 2015 Society of Chemical
Industry.
PMID- 26423557
TI - The associations of BMI trajectory and excessive weight gain with demographic and
socio-economic factors: the Adolescent Nutritional Assessment Longitudinal Study
cohort.
AB - Assessing changes in adolescents' BMI over brief periods could contribute to
detection of acute changes in weight status and prevention of overweight. The
objective of this study was to analyse the BMI trajectory and the excessive
weight gain of Brazilian adolescents over 3 years and the association with
demographic and socio-economic factors. Data regarding the BMI of 1026 students
aged between 13 and 19 years were analysed over 3 consecutive years (2010, 2011
and 2012) from the Adolescent Nutritional Assessment Longitudinal Study. Linear
mixed effects models were used to assess the BMI trajectory according to the type
of school attended (public or private), skin colour, socio-economic status and
level of maternal schooling by sex. Associations between excessive weight gain
and socio-economic variables were identified by calculation of OR. Boys attending
private schools (beta coefficient: 0.008; P=0.01), those with white skin (beta
coefficient: 0.007; P=0.04) and those whose mothers had >8 years of schooling
(beta coefficient: 0.009; P=0.02) experienced greater BMI increase than boys and
girls in other groups. Boys in private schools also presented higher excessive
weight gain compared with boys attending public schools (P=0.03). Boys attending
private schools experienced greater BMI increase and excessive weight gain,
indicating the need to develop specific policies for the prevention and reduction
of overweight in this population.
PMID- 26423558
TI - Quantitative electron phase imaging with high sensitivity and an unlimited field
of view.
AB - As it passes through a sample, an electron beam scatters, producing an exit
wavefront rich in information. A range of material properties, from electric and
magnetic field strengths to specimen thickness, strain maps and mean inner
potentials, can be extrapolated from its phase and mapped at the nanoscale.
Unfortunately, the phase signal is not straightforward to obtain. It is most
commonly measured using off-axis electron holography, but this is experimentally
challenging, places constraints on the sample and has a limited field of view.
Here we report an alternative method that avoids these limitations and is easily
implemented on an unmodified transmission electron microscope (TEM) operating in
the familiar selected area diffraction mode. We use ptychography, an imaging
technique popular amongst the X-ray microscopy community; recent advances in
reconstruction algorithms now reveal its potential as a tool for highly
sensitive, quantitative electron phase imaging.
PMID- 26423560
TI - Effects of Particle Size, Electronic Connectivity, and Incoherent Nanoscale
Domains on the Sequence of Lithiation in LiFePO4 Porous Electrodes.
AB - High-resolution X-ray microscopy is used to investigate the sequence of
lithiation in LiFePO4 porous electrodes. For electrodes with homogeneous
interparticle electronic connectivity via the carbon black network, the smaller
particles lithiate first. For electrodes with heterogeneous connectivity, the
better-connected particles preferentially lithiate. Correlative electron and X
ray microscopy also reveal the presence of incoherent nanodomains that lithiate
as if they are separate particles.
PMID- 26423559
TI - Adherence to common cardiovascular medications in patients with schizophrenia vs.
patients without psychiatric illness.
AB - OBJECTIVE: The purpose of the study was to examine whether individuals with
diagnoses of schizophrenia were differentially adherent to their statin or
angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB)
medications compared to individuals without psychiatric illness. METHOD: Using
electronic medical record data across 13 Mental Health Research Network sites,
individuals with diagnoses of schizophrenia or schizoaffective disorder receiving
two or more medication dispensings of a statin or an ACEI/ARB in 2011 (N=710)
were identified and matched on age, sex and Medicare status to controls with no
documented mental illness and two or more medication dispensings of a statin in
2011 (N=710). Medication adherence, and sociodemographic and clinical
characteristics of the study population were assessed. RESULTS: Multivariable
models indicated that having a schizophrenia diagnosis was associated with
increased odds of statin medication adherence; the odds ratio suggested a small
effect. After adjustment for medication regimen, schizophrenia no longer showed
an association with statin adherence. Having a schizophrenia diagnosis was not
associated with ACEI/ARB medication adherence. CONCLUSIONS: Compared to patients
without any psychiatric illness, individuals with schizophrenia were marginally
more likely to be adherent to their statin medications. Given that patterns of
adherence to cardioprotective medications may be different from patterns of
adherence to antipsychotic medications, improving adherence to the former may
require unique intervention strategies.
PMID- 26423561
TI - Nanomedicine of anastrozole for breast cancer: Physicochemical evaluation, in
vitro cytotoxicity on BT-549 and MCF-7 cell lines and preclinical study on rat
model.
AB - AIM: Formulation and evaluation of anastrozole, an anti-cancer drug loaded in
different biodegradable polymeric nanoparticles. MATERIALS AND METHODS: Different
carrier systems such as poly(lactide-co-glycolide) (PLGA 50:50), poly(lactic
acid) (PLA) and poly(epsilon-caprolactone) (PCL) are used to prepare
nanoparticles by simple emulsion technique. The surfactants polyvinyl alcohol and
sodium deoxycholate were studied for their use as stabilizing agents at varying
concentrations. The formulations were studied for their particle size, zeta
potential, entrapment efficiency and solid state characteristics, and also were
tested for their in vitro cytotoxicity and in vivo behavior in rats. KEY
FINDINGS: The entrapment ranged from 35 to 85%, depending on the drug-polymer
ratio used. Particle size ranged from 100 to 350nm with optimal zeta potential.
Accordingly, discrete spherical nanoparticles with smooth surface were obtained
as evidence from Field Emission Scanning Electron Microscopy (FESEM) study. The
solid state characteristics revealed dispersion of drug at the molecular level in
the polymeric matrix of nanoparticles. A non-Fickian transport with initial burst
release followed by slow release was observed with nanoparticles. The remarkable
decrease in cell viability at various time points was observed for PLGA
nanoparticles compared to other polymer matrices. The AUC(0->infinity) of PLGA,
PLA and PCL nanoparticles were found to be 4.77, 19.31 and 19.81 fold higher than
(p<0.05) anastrozole in solution, respectively. Also, pharmacokinetics study
revealed the long time circulation of anastrozole loaded polymeric nanoparticles.
SIGNIFICANCE: The results suggest that developed nanoparticles could be used
successfully for effective management of breast cancer chemotherapy.
PMID- 26423562
TI - A new cluster-based oversampling method for improving survival prediction of
hepatocellular carcinoma patients.
AB - Liver cancer is the sixth most frequently diagnosed cancer and, particularly,
Hepatocellular Carcinoma (HCC) represents more than 90% of primary liver cancers.
Clinicians assess each patient's treatment on the basis of evidence-based
medicine, which may not always apply to a specific patient, given the biological
variability among individuals. Over the years, and for the particular case of
Hepatocellular Carcinoma, some research studies have been developing strategies
for assisting clinicians in decision making, using computational methods (e.g.
machine learning techniques) to extract knowledge from the clinical data.
However, these studies have some limitations that have not yet been addressed:
some do not focus entirely on Hepatocellular Carcinoma patients, others have
strict application boundaries, and none considers the heterogeneity between
patients nor the presence of missing data, a common drawback in healthcare
contexts. In this work, a real complex Hepatocellular Carcinoma database composed
of heterogeneous clinical features is studied. We propose a new cluster-based
oversampling approach robust to small and imbalanced datasets, which accounts for
the heterogeneity of patients with Hepatocellular Carcinoma. The preprocessing
procedures of this work are based on data imputation considering appropriate
distance metrics for both heterogeneous and missing data (HEOM) and clustering
studies to assess the underlying patient groups in the studied dataset (K-means).
The final approach is applied in order to diminish the impact of underlying
patient profiles with reduced sizes on survival prediction. It is based on K
means clustering and the SMOTE algorithm to build a representative dataset and
use it as training example for different machine learning procedures (logistic
regression and neural networks). The results are evaluated in terms of survival
prediction and compared across baseline approaches that do not consider
clustering and/or oversampling using the Friedman rank test. Our proposed
methodology coupled with neural networks outperformed all others, suggesting an
improvement over the classical approaches currently used in Hepatocellular
Carcinoma prediction models.
PMID- 26423563
TI - Organization and Development of Bone Marrow Donation and Transplantation in
Poland.
AB - This paper describes bone marrow donation and transplantation in Poland in terms
of its history, current state, and information on the quality control system.
Based on data gathered from the informatics systems of the Polish Central
Unrelated Potential Bone Marrow Donor and Cord Blood Registry and the Polish
transplant registries, as well as World Marrow Donor Association statistics, we
performed an overview study to collect and compare numbers on hematopoietic stem
cells donations and transplantations in Poland in the years 2010-2014. In the
last 5 years, the number of registered potential hematopoietic stem cells donors
in Poland increased by more than 4 times, from about 146,000 to over 750,000.
During the same period, the number of patients qualified to hematopoietic stem
cells transplantation from unrelated donor increased from 557 in 2010 to 817 in
2014. We observed a striking change in the percentage of transplantations
performed in Polish centers using material collected from national donors--from
24% to 60%. This shift was also evident in the number of search procedures closed
with acceptation of Polish donors--from 27% in 2010 to 58% in 2014. Another
consequence of Polish registry growth is the increasing number of donations from
Polish donors for international patients. Between 2010 and 2014, the percent of
donation for non-national patient increased from 33% to 76%, placing Poland in
6th place in the ranking of the HSC "exporters" worldwide. Growth of
transplantation rates involves standardization process, which is a natural way of
development for national organizations in the field of HSCT because of its
international character.
PMID- 26423564
TI - The role of nutritional interventions in increasing fruit and vegetable intake in
the elderlies: a systematic review.
AB - BACKGROUND: The consumption of fruit and vegetables in old ages is particularly
important, so that the appropriate consumption amount leads to reduction in the
risk of chronic diseases. To increase consumption of fruit and vegetables and
modify consumption pattern in the elderlies, training programs and appropriate
intervention can be designed and implemented. AIMS: The study was done to assess
and compare nutritional intervention-based training methods and education using
theories and health education models for the consumption of fruits and vegetables
in the elderlies. METHODS: Electronic search using keywords of Country Review
Information Bank (Magiran), Scientific Information Database, Pub Med, Science
direct, Science, Biomed central from the beginning of March 2014 to end of April
2015 was performed. RESULTS: Ten interventional studies were assessed in this
systematic study. The interventions were divided into two groups of studies, a
total of five studies, theories and health education models were the basis of
training intervention and the other five studies that include their interventions
without the use of theories and health education models was carried out. Of ten
interventional studies, three studies as before and after and seven studies as
the intervention and control was performed. DISCUSSION: The results showed that
education-based theory and health education models have a greater impact on the
consumption of fruit and vegetables in the elderlies. CONCLUSIONS: The duration
and interventions performing method, environmental factors and educational
programs using appropriate models and theories are important on the effectiveness
of interventions to increase consumption of fruit and vegetables in the
elderliness.
PMID- 26423565
TI - Association of the COL1A1 gene polymorphisms in Mexican postmenopausal women with
fracture or with low bone mineral density at the hip.
AB - BACKGROUND AND AIMS: Osteoporosis leads to high fracture risk and evidence
suggests that genetic factors play an important role in this disease. The aim was
to evaluate the association of two polymorphisms (-1997G/T, +1245G/T) in the
collagen type1 alpha 1 gene (COL1A1) with fracture or with low bone mineral
density (BMD) at the hip in postmenopausal Mexican women. METHODS: BMD was
determined by bone densitometry and the risk factors were collected with a
questionnaire. Genotyping was performed by real-time PCR. RESULTS: The
polymorphisms were in Hardy-Weinberg equilibrium. The -1997G/+1245T haplotype
showed, after adjustment for confounders, a fourfold increased risk of hip
fracture [OR 4.32; p = 0.041 (95 % CI 1.07-17.43)]; while in the women with low
BMD at the hip, the risk was increased threefold [OR 3.36; p = 0.022 (95 % CI
1.20-9.40)]. CONCLUSIONS: The results support the association of COL1A1 gene
polymorphisms with fracture and with low BMD at the hip in Mexican population.
PMID- 26423567
TI - iBioChina and iBiology: spreading scientific knowledge together.
PMID- 26423566
TI - Characteristics of the TCR Vbeta repertoire in imatinib-resistant chronic myeloid
leukemia patients with ABL mutations.
AB - Diversity in the T cell receptor (TCR) repertoire provides a miniature defense
ability for the T cell immune system that may be related to tumor initiation and
progression. Understanding the T cell immune status of leukemia patients is
critical for establishing specific immunotherapies. Previous studies have
reported abnormal TCR repertoires and clonally expanded TCR Vbeta T cells in
chronic myeloid leukemia in chronic phase (CP-CML). In this study, we
investigated the distribution and clonality of the TCR Vbeta repertoire in 4
cases with imatinib-resistant CML in blast crisis (BC-CML) with abelson murine
leukemia viral oncogene homolog 1 (ABL1) kinase domain mutations (KDMs).
Examination of TCR V expression and clonality was performed by reverse
transcription-polymerase chain reaction (RT-PCR) and GeneScan analysis.
Significantly skewed TCR Vbeta repertoires were observed in BC-CML patients with
different KDMs, and 4 to 8 oligoclonally expanded TCR Vbeta subfamilies could be
identified in each sample. Intriguingly, a relatively highly expanded Vbeta9
clone with the same length as complementarity- determining region 3 (CDR3) (139
bp) was found in all three CML patients in lymphoid blast crisis (LBC-CML) who
had different KDMs, but the clone was not detected in the only CML patient in
myeloid blast crisis (MBC-CML). In conclusion, restricted TCR Vbeta repertoire
expression and decreased clone complexity was a general phenomenon observed in
the BC-CML patients with different KDMs, indicating the T-cell immunodeficiency
of these patients. In addition, clonally expanded Vbeta9 T cell clones may
indicate a specific immune response to leukemia-associated antigens in LBC-CML
patients.
PMID- 26423568
TI - Public impact, prevention, and treatment of cataracts.
PMID- 26423569
TI - Do Wildfires Promote Woody Species Invasion in a Fire-Adapted Ecosystem? Post
fire Resprouting of Native and Non-native Woody Plants in Central Argentina.
AB - We asked whether prescribed fire could be a useful management tool to reduce
invasion by non-native plants in an ecosystem where native plants are supposed to
be adapted to fires. Specifically, we compare the post-fire resprouting response
of native and non-native woody species in Chaco Serrano forest of central
Argentina. The measurements were carried out in five burnt areas where we
selected ten native and seven non-native species. Our response variables were (1)
post-fire survival, (2) types of resprouts, and (3) the growth of the resprouts.
Our main results show that one year after the fire, survivals of native and non
native species were 0.84 and 0.89, respectively, with variances in survival seven
times smaller in the native species group. Type of resprout was also less
variable in native species, while growth of the resprouts was similar in native
and non-native groups. We interpret that in most cases, the burning a forest with
mixed native and non-native plants through prescribed fires will not
differentially stop the invasion by non-native woody species even in ecosystems
which are presumed to be relatively resistant to fires such as our study area.
PMID- 26423570
TI - Biomarkers of aging, life span and spontaneous carcinogenesis in the wild type
and HER-2 transgenic FVB/N female mice.
AB - FVB/N wild type and transgenic HER-2/neu FVB/N female mice breed at N.N. Petrov
Research Institute of Oncology were under observation until natural death without
any special treatment. Age-related dynamics of body weight, food consumption and
parameters of carbohydrate and lipid metabolism, level of nitric oxide, malonic
dialdehyde, catalase, Cu, Zn-superoxide dismutase, vascular endothelial growth
factor were studied in both mice strains. The parameters of life span and tumor
pathology were studied as well. Cancer-prone transgenic HER-2/neu mice developed
in 100 % multiple mammary adenocarcinomas and died before the age of 1 year.
Forty tree percent of long-lived wild type mice survived the age of 2 years and
19 %-800 days. The total tumor incidence in wild type mice was 34 %. The age
associated changes in the level of serum IGF-1, glucose and insulin started much
earlier in transgene HER-2/neu mice as compared with wild type FVB/N mice. It was
suggested that transgenic HER-2/neu involves in initiation of malignization of
mammary epithelial cells but also in acceleration of age-related hormonal and
metabolic changes in turn promoting mammary carcinogenesis.
PMID- 26423571
TI - The influence of Streptococcus pneumoniae nasopharyngeal colonization on the
clinical outcome of the respiratory tract infections in preschool children.
AB - BACKGROUND: Streptococcus pneumoniae (SPn) is an important pathogen causing a
variety of clinical manifestations. The effects of SPn nasopharyngeal
colonization on respiratory tract infections are poorly studied. We evaluated the
association of SPn colonization with features of respiratory tract infections.
METHODS: Children under the age of 6 years who visited a primary care physician
because of respiratory tract infections were enrolled in the study. History was
taken, children were clinically assessed by the physician, and nasopharyngeal
swabs were obtained and cultured for SPn. Positive samples were serotyped.
Associations of SPn colonization with clinical signs and symptoms, recovery
duration, absence from day care centre, frequencies of specific diagnoses, and
treatment with antimicrobials were evaluated. RESULTS: In total 900 children were
enrolled. The prevalence of SPn colonization was 40.8 % (n = 367). There were
minor differences between male and female subjects (199 of 492, 40.4 % vs 168 of
408, 41.2 %, p = 0.825). Children with and without siblings had similar
colonization rates (145 of 334, 43.4 % vs 219 of 562, 39.0 %, p = 0.187).
Clinical signs and symptoms were not associated with SPn colonization. Children
colonized with SPn had longer recovery duration compared to non-colonized
children (114 of 367, 31.1 % vs 98 of 533, 18.4 %, p < 0.001) and were longer
absent from day care (270 of 608, 44.4 % vs 94 of 284, 33.1 %, p = 0.001).
Pneumonia, sinusitis, and acute otitis media were more frequently diagnosed in
children colonized with SPn. Children attending day care centres had
significantly higher prevalence of SPn colonization (270 of 367, 44.4 % vs 338 of
533, 33.1 %, p = 0.001). Children with pneumonia, sinusitis and acute otitis
media were more frequently treated with antimicrobials than children with other
diagnoses. CONCLUSIONS: SPn nasopharyngeal colonization has a negative impact on
the course of respiratory tract infection, likely because of SPn being the cause
of the disease or a complicating factor. It is also associated with and may be
responsible for higher frequencies of bronchitis, pneumonia, acute otitis media,
sinusitis and the need of antimicrobial treatment.
PMID- 26423572
TI - Thermal effects of lambda = 808 nm GaAlAs diode laser irradiation on different
titanium surfaces.
AB - Diode lasers are widely used in dental laser treatment, but little is known about
their thermal effects on different titanium implant surfaces. This is a key issue
because already a 10 degrees C increase over the normal body temperature can
induce bone injury and compromise osseo-integration. The present study aimed at
evaluating the temperature changes and surface alterations experienced by
different titanium surfaces upon irradiation with a lambda = 808 nm diode laser
with different settings and modalities. Titanium discs with surfaces mimicking
different dental implant surfaces including TiUnite and anodized, machined
surfaces were laser-irradiated in contact and non-contact mode, and with and
without airflow cooling. Settings were 0.5-2.0 W for the continuous wave mode and
10-45 MUJ, 20 kHz, 5-20 MUs for the pulsed wave mode. The results show that the
surface characteristics have a marked influence on temperature changes in
response to irradiation. The TiUnite surface, corresponding to the osseous
interface of dental implants, was the most susceptible to thermal rise, while the
machined surfaces, corresponding to the implant collar, were less affected. In
non-contact mode and upon continuous wave emission, the temperature rose above
the 50 degrees C tissue damage threshold. Scanning electron microscopy
investigation of surface alterations revealed that laser treatment in contact
mode resulted in surface scratches even when no irradiation was performed. These
findings indicate that the effects of diode laser irradiation on implant surfaces
depend on physical features of the titanium coating and that in order to avoid
thermal or physical damage to implant surface the irradiation treatment has to be
carefully selected.
PMID- 26423573
TI - Needs and Supports of People with Intellectual Disability and Their Families in
Catalonia.
AB - BACKGROUND: The study assesses the support needs of individuals with intellectual
disability and their families in Catalonia. The present authors examine family
quality of life (FQoL), identify the individual services required and assess
families' perceptions of the extent to which their family member with
intellectual disability and they themselves receive the services they need.
MATERIALS AND METHODS: The N&S questionnaire (Needs and Supports for people with
intellectual disability and their families) was administered to 2160 families
with a family member with intellectual disability aged under 70 in Catalonia
(Spain). RESULTS: Overall mean FQoL was quite high. FQoL was associated with
family income, education, employment and percentage level of disability. Neither
people with intellectual disability nor their families receive the specific
support they need. CONCLUSIONS: Besides providing specific support for
individuals with intellectual disability, local policymakers and practitioners
should apply a family-centred approach to the provision of support for families
in order to improve FQoL.
PMID- 26423574
TI - Colectomy for constipation: time trends and impact based on the US Nationwide
Inpatient Sample, 1998-2011.
AB - BACKGROUND: Current guidelines include subtotal colectomy as treatment for
refractory slow transit constipation. AIM: To use the US Nationwide Inpatient
Sample (NIS) (1998-2011) and longitudinal data from the State Inpatient Database
(2005-2011), comparable to NIS, to examine colectomy rates, in-hospital morbidity
and emergency department (ED) visits or readmissions among patients treated for
constipation. METHODS: Colectomies for any reason were identified based on the
primary procedural code (ICD-9-CM 45.8x). Index hospitalisations were defined by
the primary diagnosis of constipation (ICD-9-CM 564.x) associated with the
primary procedural code for colectomy (ICD-9-CM45.8x) after exclusion of other
diseases associated with colectomy. Demographic variables, comorbidities,
complications and adverse events during the hospitalisation were captured, and ED
visits and admissions were recorded for periods before and after colectomy.
RESULTS: Nationally, colectomies for constipation rose from 104 procedures in
1998 (1.2% of annual colectomies) to 311 in 2011 (2.4% of annual colectomies).
While there were no perioperative deaths, perioperative complications occurred in
42.7% of patients during the index hospitalisation. Longitudinal data were
analysed for 181 patients, with similar perioperative complications and a
readmission rate of 28.9% within the first 30 days after the index
hospitalisation. Resource utilisation was tracked for a median time of 630 (0
2386) before and 463 (0-2204) days after colectomy with unchanged ED visits
(median: 2 vs. 2, P = 0.21), but increased hospitalisations (median: 1 vs. 2, P =
0.003). CONCLUSIONS: Colectomy rates for constipation are rising, are associated
with significant morbidity and do not decrease resource utilisation, raising
questions about the true benefit of surgery for slow transit constipation.
PMID- 26423575
TI - Bayesian network analysis of multi-compartmentalized immune responses in a murine
model of sepsis and direct lung injury.
AB - BACKGROUND: Inflammatory disease processes involve complex and interrelated
systems of mediators. Determining the causal relationships among these mediators
becomes more complicated when two, concurrent inflammatory conditions occur. In
those cases, the outcome may also be dependent upon the timing, severity and
compartmentalization of the insults. Unfortunately, standard methods of
experimentation and analysis of data sets may investigate a single scenario
without uncovering many potential associations among mediators. However, Bayesian
network analysis is able to model linear, nonlinear, combinatorial, and
stochastic relationships among variables to explore complex inflammatory disease
systems. In these studies, we modeled the development of acute lung injury from
an indirect insult (sepsis induced by cecal ligation and puncture) complicated by
a direct lung insult (aspiration). To replicate multiple clinical situations, the
aspiration injury was delivered at different severities and at different time
intervals relative to the septic insult. For each scenario, we measured numerous
inflammatory cell types and cytokines in samples from the local compartments
(peritoneal and bronchoalveolar lavage fluids) and the systemic compartment
(plasma). We then analyzed these data by Bayesian networks and standard methods.
RESULTS: Standard data analysis demonstrated that the lung injury was actually
reduced when two insults were involved as compared to one lung injury alone.
Bayesian network analysis determined that both the severity of lung insult and
presence of sepsis influenced neutrophil recruitment and the amount of injury to
the lung. However, the levels of chemoattractant cytokines responsible for
neutrophil recruitment were more strongly linked to the timing and severity of
the lung insult compared to the presence of sepsis. This suggests that something
other than sepsis-driven exacerbation of chemokine levels was influencing the
lung injury, contrary to previous theories. CONCLUSIONS: To our knowledge, these
studies are the first to use Bayesian networks together with experimental studies
to examine the pathogenesis of sepsis-associated lung injury. Compared to
standard statistical analysis and inference, these analyses elucidated more
intricate relationships among the mediators, immune cells and insult-related
variables (timing, compartmentalization and severity) that cause lung injury.
Bayesian networks are an effective tool for evaluating complex models of
inflammation.
PMID- 26423576
TI - Financial toxicity: a potential side effect of prostate cancer treatment among
Australian men.
AB - The purpose of this study was to understand the extent, nature and variability of
the current economic burden of prostate cancer among Australian men. An online
cross-sectional survey was developed that combined pre-existing economic measures
and new questions. With few exceptions, the online survey was viable and
acceptable to participants. The main outcomes were self-reported out-of-pocket
costs of prostate cancer diagnosis and treatment, changes in employment status
and household finances. Men were recruited from prostate cancer support groups
throughout Australia. Descriptive statistical analyses were undertaken. A total
of 289 men responded to the survey during April and June 2013. Our study found
that men recently diagnosed (within 16 months of the survey) (n = 65) reported
spending a median AU$8000 (interquartile range AU$14 000) for their cancer
treatment while 75% of men spent up to AU$17 000 (2012). Twenty per cent of all
men found the cost of treating their prostate cancer caused them 'a great deal'
of distress. The findings suggest a large variability in medical costs for
prostate cancer treatment with 5% of men spending $250 or less in out-of-pocket
expenses and some men facing very high costs. On average, respondents in paid
employment at diagnosis stated that they had retired 4-5 years earlier than
planned.
PMID- 26423577
TI - Development of a pan-Babesia FRET-qPCR and a survey of livestock from five
Caribbean islands.
AB - BACKGROUND: Babesia spp. are tick-borne protozoan hemoparasites and the second
most common blood-borne parasites of mammals, in particular domestic animals. We
used the Clustal Multiple Alignment program and 18S rRNA gene sequences of 22
Babesia species from GenBank to develop a PCR that could detect a wide variety of
Babesia spp. in a single reaction. The pan-Babesia FRET-qPCR we developed
reliably detected B. gibsoni, B. canis, B. vogeli, B. microti, B. bovis, and B.
divergens under controlled conditions but did not react with closely related
species, mainly Hepatozoon americanum, Theileria equi, and Toxoplasma gondii.
RESULTS: When we tested the pan-Babesia FRET-qPCR on DNA of whole blood from 752
cattle, sheep, goats, donkeys and horses from five Caribbean islands, we detected
Babesia spp. expected to be present in the animals, mainly B. bovis and B.
bigemina in cattle and B. caballi in horses and donkeys. Further, we found that
animals were not uncommonly infected with species of Babesia usually associated
with other hosts, mainly B. vogeli and B. gibsoni in cattle, sheep and goats, B.
rossi in goats, and B. caballi in goats and sheep. Finally, the pan-Babesia FRET
qPCR enabled us to identify unknown species of Babesia in cattle, goats, sheep
and donkeys. CONCLUSIONS: Overall, 70 % (525/752) of the animals we tested were
positive confirming earlier limited studies that infections with Babesia spp. are
common in livestock in the Caribbean.
PMID- 26423578
TI - Po2 cycling protects diaphragm function during reoxygenation via ROS, Akt, ERK,
and mitochondrial channels.
AB - Po2 cycling, often referred to as intermittent hypoxia, involves exposing tissues
to brief cycles of low oxygen environments immediately followed by hyperoxic
conditions. After experiencing long-term hypoxia, muscle can be damaged during
the subsequent reintroduction of oxygen, which leads to muscle dysfunction via
reperfusion injury. The protective effect and mechanism behind Po2 cycling in
skeletal muscle during reoxygenation have yet to be fully elucidated. We
hypothesize that Po2 cycling effectively increases muscle fatigue resistance
through reactive oxygen species (ROS), protein kinase B (Akt), extracellular
signal-regulated kinase (ERK), and certain mitochondrial channels during
reoxygenation. Using a dihydrofluorescein fluorescent probe, we detected the
production of ROS in mouse diaphragmatic skeletal muscle in real time under
confocal microscopy. Muscles treated with Po2 cycling displayed significantly
attenuated ROS levels (n = 5; P < 0.001) as well as enhanced force generation
compared with controls during reperfusion (n = 7; P < 0.05). We also used
inhibitors for signaling molecules or membrane channels such as ROS, Akt, ERK, as
well as chemical stimulators to close mitochondrial ATP-sensitive potassium
channel (KATP) or open mitochondrial permeability transition pore (mPTP). All
these blockers or stimulators abolished improved muscle function with Po2 cycling
treatment. This current investigation has discovered a correlation between KATP
and mPTP and the Po2 cycling pathway in diaphragmatic skeletal muscle. Thus we
have identified a unique signaling pathway that may involve ROS, Akt, ERK, and
mitochondrial channels responsible for Po2 cycling protection during
reoxygenation conditions in the diaphragm.
PMID- 26423579
TI - Water transport running deep. Focus on "Deep proteomic profiling of vasopressin
sensitive collecting duct cells".
PMID- 26423581
TI - An Unusual Case of Reversible Empty Sella.
AB - CONTEXT: An empty sella is a relatively common condition, often being an
incidental finding at MRI or CT scan. It can develop because of the intrasellar
herniation of Cerebro-spinal Fluid (CSF) and arachnoid membrane through an absent
or rudimentary diaphragm sellae in concomitance of a sudden and even transient
increment of intracranial pressure, leading to a picture in which the pituitary
is flattened along the floor of the sella. CASE DESCRIPTION: A young female with
headache, nausea, dizziness, diplopia and visual impairment showed an empty sella
on MRI and increased CSF pressure at the lumbar puncture. After an initial
improvement, there was a progressive worsening of the headache, especially in
orthostatic position, with transient relief after bed rest and hydration. At MRI
the empty sella was no longer evident, cerebellar tonsils were displaced in the
occipital foramen and there was an impregnation of the meninges after contrast
medium, a picture of CSF hypotension, probably due to the previously performed
lumbar puncture causing a fistula with leak of CSF and consequent disappearance
of the empty sella. The patient gradually improved after being submitted to
epidural blood patch. CONCLUSIONS: The case here reported demonstrates that an
empty sella can be a reversible condition in rare cases. Its disappearance can be
due to the reduction in intracranial pressure caused by the lumbar puncture
itself. The changes in the characteristics of the headache, in particular its
worsening in the orthostatic position, should lead to the suspicion of CSF leak
through a fistula and consequent intracranial hypotension, a dangerous and
sometimes life-threatening condition.
PMID- 26423580
TI - Purification, characterization and crystallization of the F-ATPase from
Paracoccus denitrificans.
AB - The structures of F-ATPases have been determined predominantly with mitochondrial
enzymes, but hitherto no F-ATPase has been crystallized intact. A high-resolution
model of the bovine enzyme built up from separate sub-structures determined by X
ray crystallography contains about 85% of the entire complex, but it lacks a
crucial region that provides a transmembrane proton pathway involved in the
generation of the rotary mechanism that drives the synthesis of ATP. Here the
isolation, characterization and crystallization of an integral F-ATPase complex
from the alpha-proteobacterium Paracoccus denitrificans are described. Unlike
many eubacterial F-ATPases, which can both synthesize and hydrolyse ATP, the P.
denitrificans enzyme can only carry out the synthetic reaction. The mechanism of
inhibition of its ATP hydrolytic activity involves a zeta inhibitor protein,
which binds to the catalytic F1-domain of the enzyme. The complex that has been
crystallized, and the crystals themselves, contain the nine core proteins of the
complete F-ATPase complex plus the zeta inhibitor protein. The formation of
crystals depends upon the presence of bound bacterial cardiolipin and
phospholipid molecules; when they were removed, the complex failed to
crystallize. The experiments open the way to an atomic structure of an F-ATPase
complex.
PMID- 26423582
TI - Unilateral sling transection for patients with postoperative voiding dysfunction
after transobturator sling surgery.
PMID- 26423583
TI - Modeling of T2* decay in vertebral bone marrow fat quantification.
AB - Bone marrow fat fraction mapping using chemical shift encoding-based water-fat
separation is becoming a useful tool in investigating the association between
bone marrow adiposity and bone health and in assessing cancer treatment-induced
bone marrow damage. Vertebral bone marrow is characterized by short T2*
relaxation times, which are in general different for the water and fat components
and can confound fat quantification. The purpose of the present study is to
compare different approaches to T2* correction in chemical shift encoding-based
water-fat imaging of vertebral bone marrow using single-voxel MRS as reference.
Eight-echo gradient-echo imaging and single-voxel MRS measurements were made on
the spine (L3-L5) of 25 healthy volunteers. Different approaches were evaluated
for correction of T2* effects: (a) single-T2* correction, (b) dual-T2*
correction, (c) T2' correction using the a priori-known T2 from the MRS at each
vertebral body and (d) T2' correction using the a priori-known T2 equal to
previously measured average values. Dual-T2* correction resulted in noisier
imaging fat fraction maps than single-T2* correction or T2' correction using a
priori-known T2. Linear regression analysis between imaging and MRS fat fraction
showed a slope significantly different from 1 when using single-T2* correction
(R(2) = 0.96) or dual-T2* correction (R(2) = 0.87). T2' correction using the a
priori-known T2 resulted in a slope not significantly different from 1, an
intercept significantly different from 0 (between 2.4% and 3%) and R(2) = 0.96.
Therefore, a T2' correction using a priori-known T2 can remove the fat fraction
bias induced by the difference in T2* between water and fat components without
degrading noise performance in fat fraction mapping of vertebral bone marrow.
PMID- 26423585
TI - Variation in outcome of acute myocardial infarction in Sweden and the UK may be
due to population heterogeneity in the UK.
PMID- 26423586
TI - Laser Microdissection.
AB - Laser microdissection (LM) offers a relatively rapid and precise method of
isolating and removing specified cells from complex tissues for subsequent
analysis of their RNA, DNA, protein or metabolite content, thereby allowing
assessment of the role of different cell types in the normal physiological or
disease processes being studied. In this unit, protocols for the preparation of
mammalian frozen tissues, fixed tissues, and cytologic specimens for LM,
including tissue freezing, tissue processing and paraffin embedding, histologic
sectioning, cell processing, hematoxylin and eosin staining,
immunohistochemistry, and image-guided cell targeting are presented. Also
provided are recipes for generating lysis buffers for the recovery of nucleic
acids and proteins. The Commentary section addresses the types of specimens that
can be utilized for LM and approaches to staining of specimens for cell
visualization. Emphasis is placed on the preparation of tissue or cytologic
specimens as this is critical to effective LM.
PMID- 26423587
TI - Laser Microdissection-Mediated Isolation and In Vitro Transcriptional
Amplification of Plant RNA.
AB - Laser microdissection of cells allows for isolation of specific cells of interest
for downstream analyses including transcriptional profiling. Plant cells present
unique challenges for laser microdissection due to their cellulosic cell walls
and large vacuoles. Here we present protocols for plant tissue preparation, laser
microdissection of select plant cells, and linear amplification of RNA from
dissected cells. Linear amplification of RNA from dissected cells allows
sufficient RNA for subsequent quantitative analysis by RT-PCR, microarray, or RNA
sequencing.
PMID- 26423584
TI - Prophylactic antibiotic regimens in tumour surgery (PARITY): a pilot multicentre
randomised controlled trial.
AB - OBJECTIVE: Clinical studies of patients with bone sarcomas have been challenged
by insufficient numbers at individual centres to draw valid conclusions. Our
objective was to assess the feasibility of conducting a definitive multi-centre
randomised controlled trial (RCT) to determine whether a five-day regimen of post
operative antibiotics, in comparison to a 24-hour regimen, decreases surgical
site infections in patients undergoing endoprosthetic reconstruction for lower
extremity primary bone tumours. METHODS: We performed a pilot international multi
centre RCT. We used central randomisation to conceal treatment allocation and
sham antibiotics to blind participants, surgeons, and data collectors. We
determined feasibility by measuring patient enrolment, completeness of follow-up,
and protocol deviations for the antibiotic regimens. RESULTS: We screened 96
patients and enrolled 60 participants (44 men and 16 women) across 21 sites from
four countries over 24 months (mean 2.13 participants per site per year, standard
deviation 2.14). One participant was lost to follow-up and one withdrew consent.
Complete data were obtained for 98% of eligible patients at two weeks, 83% at six
months, and 73% at one year (the remainder with partial data or pending queries).
In total, 18 participants missed at least one dose of antibiotics or placebo post
operatively, but 93% of all post-operative doses were administered per protocol.
CONCLUSIONS: It is feasible to conduct a definitive multi-centre RCT of post
operative antibiotic regimens in patients with bone sarcomas, but further
expansion of our collaborative network will be critical. We have demonstrated an
ability to coordinate in multiple countries, enrol participants, maintain
protocol adherence, and minimise losses to follow-up. Cite this article: Bone
Joint Res;4:154-162.
PMID- 26423588
TI - RNA Interference and MicroRNA-Mediated Silencing.
AB - RNA interference (RNAi) and microRNA-mediated silencing cause sequence-specific
silencing of target genes. This overview will give a brief description of how
RNAi and microRNAs were discovered, how small RNAs silence their targets, and
what the functions of small RNAs are. Since the discovery of RNAi, RNAi has been
widely used in studies of gene function, including high-throughput screening. The
unit will briefly describe how RNAi is used in different model systems, and how
to analyze the function of endogenous small RNAs.
PMID- 26423589
TI - Genome Editing in Human Cells Using CRISPR/Cas Nucleases.
AB - The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR
associated (Cas) system has been broadly adopted for highly efficient genome
editing in a variety of model organisms and human cell types. Unlike previous
genome editing technologies such as zinc finger nucleases (ZFNs) and
transcription activator-like effector nucleases (TALENs), CRISPR/Cas technology
does not require complex protein engineering and can be utilized by any
researcher proficient in basic molecular biology and cell culture techniques.
This unit describes protocols for design and cloning of vectors expressing single
or multiplex gRNAs, for transient transfection of human cell lines, and for
quantitation of mutation frequencies by T7 endonuclease I assay. These protocols
also include guidance for using two improvements that increase the specificity of
CRISPR/Cas nucleases: truncated gRNAs and dimeric RNA-guided FokI nucleases.
PMID- 26423590
TI - Transcriptome-Wide Identification of Pseudouridine Modifications Using Pseudo
seq.
AB - A diverse array of post-transcriptional modifications is found in RNA molecules
from all domains of life. While the locations of RNA modifications are well
characterized in abundant noncoding RNAs, modified sites in less abundant mRNAs
are just beginning to be discovered. Recent work has revealed hundreds of
previously unknown and dynamically regulated pseudouridines (Psi) in mRNAs from
diverse organisms. This unit describes Pseudo-seq, an efficient, high-resolution
method for identification of Psis genome-wide. This unit includes methods for
isolation of RNA from S. cerevisiae, preparation of Pseudo-seq libraries from RNA
samples, and identification of sites of pseudouridylation from the sequencing
data. Pseudo-seq is applicable to any organism or cell type, facilitating rapid
identification of novel pseudouridylation events.
PMID- 26423591
TI - Overview of Target Enrichment Strategies.
AB - Target enrichment is commonly used in next generation sequencing (NGS) workflows
to eliminate genomic DNA regions that are not of interest for a particular
experiment. By only targeting specific regions such as exons, one can obtain
greater depth of DNA sequencing coverage for regions of interest or increase the
sampling numbers of individuals, thereby saving both time and cost. This overview
of target enrichment strategies provides a high-level review of distinct
approaches to capture specific sequences: (a) hybridization-based strategies, (b)
transposon-mediated fragmentation (tagmentation), (c) molecular inversion probes
(MIPs), and (d) singleplex and multiplex polymerase chain reaction (PCR) target
enrichment. Strategies for assay design and performance criteria are also
discussed. Other platforms currently in development are also briefly described.
PMID- 26423592
TI - Questions that need clarifying before implementation of the Ossebo balance
training programme.
PMID- 26423593
TI - Alternative competition-induced digestive strategies yield equal growth, but
constrain compensatory growth in red-eyed treefrog larvae.
AB - Compensatory growth is well documented across taxa and provides a fitness
advantage to animals who would otherwise reach a smaller reproductive size. We
investigated the role of competition-induced gut plasticity in facilitating a
compensatory response in red-eyed treefrog larvae. We reared larvae at low,
medium, and high densities with different per capita resources, environments
known to produce individuals with long and short guts. We then transferred larvae
to competitively equal environments to determine if longer guts provided an
advantage when resources became available. We predicted that larvae from higher
densities with longer guts would exhibit hyperphagia and compensatory growth. We
measured growth over 1-week, as well as the time to and size at metamorphosis. To
assess mechanisms underlying the growth response, we measured diet transit time
and intake. Growth, development, and metamorph snout-vent length did not differ
between larvae with long and short guts. Instead, different gut lengths were
associated with dramatically different feeding strategies. Medium- and high
density larvae fed at rates far below what their guts could accommodate. However,
the combination of low intake and longer guts extended diet transit times,
presumably increasing digestibility. This unexpected strategy achieved the same
results as that of low-density larvae, which ate twice as much food, but passed
it more quickly through a shorter gut. The lack of a compensatory response may be
attributed to the costs of accelerated growth and weak seasonal time constraints
in the tropics. This suggests that although compensatory growth is widespread
among animals, expression of the response may vary with environmental context. J.
Exp. Zool. 323A: 778-788, 2015. (c) 2015 Wiley Periodicals, Inc.
PMID- 26423594
TI - Histopathologic features of erythematous papulopustular eruption to epidermal
growth factor receptor inhibitors in cancer patients.
AB - BACKGROUND: Erythematous papulopustular eruption (EPPE) is the most frequent skin
adverse event to epidermal growth factor receptor (EGFR) inhibitors but its
histopathologic features have been poorly studied. As EPPE is a strong predictor
of patient's treatment response, the EPPE histopathologic features and their
correlations with skin eruption severity and involved drug were investigated.
METHOD: An involved skin biopsy was carried out in 39 informed patients treated
with EGFR inhibitors (mainly cetuximab and erlotinib). The cutaneous changes in
hematoxylin-eosin stained sections were evaluated. RESULTS: The EPPE to EGFR
inhibitors is histopathologically characterized by neutrophilic subcorneal or
intraepidermal pustules and polymorphous infiltrate of the superficial dermis
during the earliest phases and by lymphocytic perifolliculitis and/or suppurative
folliculitis at a later phase. The widespread dermis inflammation was more
frequent in severe EPPEs and in patients treated with cetuximab, while the hair
follicle inflammation was observed only in mild/moderate EPPEs. CONCLUSION: Our
study shows the histopathologic signs of EPPE and their correlation with clinical
severity and the offending drug.
PMID- 26423595
TI - Planned wedge size compared to achieved advancement in dogs undergoing the
modified Maquet procedure.
AB - OBJECTIVES: To evaluate the patellar ligament to tibial plateau angle (PL-TPA)
and amount of achieved advancement in dogs that underwent the modified Maquet
procedure; compare wedge sizes recommended using two different planning
techniques (Orthomed and modified tibial tuberosity advancement); and evaluate
anatomical factors that predict the wedge size required to obtain a 90 degrees
PL-TPA. METHODS: Pre- and postoperative radiographs of dogs that had a modified
Maquet procedure performed were evaluated for the following: calculated wedge
size using two different planning techniques, the actual wedge size used, the
achieved tibial tuberosity advancement, and the changes in PL-TPA. Anatomical
measurements of the tibia were evaluated and correlated with the actual wedge
size. RESULTS: Of the 38 modified Maquet procedures identified, 53% (n = 20) had
a PL-TPA of 90 degrees +/- 5 degrees . Actual achieved advancement of the tibial
tuberosity was 30% less than the wedge size used. Changes in PL-TPA and tibial
width persisted at eight weeks postoperatively without loss of advancement. The
two planning techniques did not result in a significantly different selection of
wedge size. CLINICAL RELEVANCE: Current planning techniques for the modified
Maquet procedure result in under-advancement of the tibial tuberosity. Both
measurement techniques evaluated do not result in appropriate advancement.
PMID- 26423596
TI - Potential estrogenic effects of wastewaters on gene expression in Pimephales
promelas and fish assemblages in streams of southeastern New York.
AB - Direct linkages between endocrine-disrupting compounds (EDCs) from municipal and
industrial wastewaters and impacts on wild fish assemblages are rare. The levels
of plasma vitellogenin (Vtg) and Vtg messenger ribonucleic acid (mRNA) in male
fathead minnows (Pimephales promelas) exposed to wastewater effluents and
dilutions of 17alpha-ethinylestradiol (EE2), estrogen activity, and fish
assemblages in 10 receiving streams were assessed to improve understanding of
important interrelations. Results from 4-d laboratory assays indicate that EE2,
plasma Vtg concentration, and Vtg gene expression in fathead minnows, and 17beta
estradiol equivalents (E2Eq values) were highly related to each other (R(2) =
0.98-1.00). Concentrations of E2Eq in most effluents did not exceed 2.0 ng/L,
which was possibly a short-term exposure threshold for Vtg gene expression in
male fathead minnows. Plasma Vtg in fathead minnows only increased significantly
(up to 1136 MUg/mL) in 2 wastewater effluents. Fish assemblages were generally
unaffected at 8 of 10 study sites, yet the density and biomass of 79% to 89% of
species populations were reduced (63-68% were reduced significantly) in the
downstream reach of 1 receiving stream. These results, and moderate to high E2Eq
concentrations (up to 16.1 ng/L) observed in effluents during a companion study,
suggest that estrogenic wastewaters can potentially affect individual fish, their
populations, and entire fish communities in comparable systems across New York,
USA.
PMID- 26423597
TI - Does alvimopan enhance return of bowel function in laparoscopic gastrointestinal
surgery? A meta-analysis.
AB - BACKGROUND: Postoperative ileus (POI) remains a major impediment in patient
recovery and leads to longer lengths of stay at the hospital, readmission rates,
and hospital costs. Alvimopan, a mu-opioid receptor antagonist, lowers POI
incidence following open gastrointestinal surgery, however, little is known about
its role on POI prevention among patients undergoing laparoscopic
gastrointestinal surgery. METHODS: A comprehensive search of PubMed/MEDLINE,
Scopus, CINAHL, and Cochrane databases was performed (December 2014). Meta
analysis was performed using the Mantel-Haenszel (fixed effects) model with odds
ratio (OR) to assess prevention of POI and hospital readmission. RESULTS: Five
studies were included in the final analysis. Pooling 4 of 5 studies, there was
over a 75% relative risk reduction in POI development when patients were given
alvimopan compared to placebo (OR 0.24, 95%CI 0.12-0.51, P=0.02). The number
needed to treat with alvimopan to prevent one POI episode was 11 patients. There
was a modest reduction in the length of hospitalization between 0.2 and 1.6 days.
There did not appear to be a difference in frequency of 30-day readmission rate
among the alvimopan group compared to placebo (OR 1.15, 95%CI 0.54-2.45, P=0.62).
CONCLUSION: Overall, there was a 75% relative risk reduction in POI development
among patients undergoing laparoscopic gastrointestinal surgery. However, there
did not appear to be a significant reduction in all-cause 30-day readmission rate
or length of hospitalization. Future studies will need to address which subset of
patients undergoing laparoscopic gastrointestinal surgery will benefit most from
alvimopan.
PMID- 26423598
TI - Triaxial system in bronchial arterial embolization for haemoptysis using N-butyl
2-cyanoacrylate.
AB - OBJECTIVE: The application of bronchial artery embolization (BAE) using N-butyl-2
cyanoacrylate (NBCA) for haemoptysis was recently reported to be useful. A triple
co-axial (triaxial) system consisting of a 4-Fr catheter, 2.7-Fr microcatheter
and 1.9-Fr no-taper microcatheter has been developed. The aim of the present
study was to evaluate the usefulness of the triaxial system in BAE using NBCA.
METHODS: 12 patients with haemoptysis, 8 males and 4 females with a median age of
64 years (range, 49-88 years), underwent BAE between August 2012 and October
2014. Medical records and images were reviewed, and the technical success rate,
clinical success rate, haemoptysis-free rate and complications were evaluated.
Technical success was defined as the complete cessation of the target artery as
confirmed by digital subtraction angiography, whereas clinical success was
defined as the cessation of haemoptysis within 24 h of BAE. Recurrent haemoptysis
was defined as a total of >30 ml of bleeding per day. RESULTS: The target artery
was embolized successfully in all patients, and the technical success rate was
100% (12/12). The cessation of haemoptysis was achieved in 11 out of 12 patients
within 24 h, and thus, the clinical success rate was 92% (11/12). The 6-, 12- and
24-month haemoptysis-free rates were 89%, 89% and 76%, respectively. No patients
exhibited any signs of complications such as spinal ischaemia. CONCLUSION: BAE
using the triaxial system and NBCA appears to be a useful and safe procedure for
haemoptysis. ADVANCES IN KNOWLEDGE: The triaxial system contributes to safe and
effective BAE using NBCA.
PMID- 26423599
TI - Perfusion-based assessment of disease activity in untreated and treated patients
with aortitis and chronic periaortitis: correlation with CT morphological,
clinical and serological data.
AB - OBJECTIVE: To evaluate the role of perfusion-based assessment of inflammatory
activity in patients with treated and untreated aortitis and chronic periaortitis
as compared with clinical and serological markers. METHODS: 35 patients (20
females; median age 66 years) with (peri) aortitis were retrospectively
evaluated. All patients had clinical symptoms prompting at the time of imaging.
All patients first underwent whole-body contrast-enhanced CT and subsequently
segmental volume perfusion CT for assessment of the degree of vascularization of
(peri) aortitis as a surrogate marker for inflammatory activity. Blood flow,
blood volume, volume transfer constant (k-trans), time to peak and mean transit
time were determined. The thickness of the increased connective tissue formation
was measured. Perfusion data were correlated with clinical symptoms and acute
phase inflammatory parameters such as C-reactive protein (CRP), erythrocyte
sedimentation rate (ESR) and leukocyte number. RESULTS: 21 of 35 patients were
untreated and 14 of 35 had previous/ongoing immunosuppression. The interobserver
agreement was good (kappa = 0.78) for all perfusion parameters. Average values of
perfusion parameters were higher in untreated patients but remained abnormally
elevated in treated patients as well. Perfusion data and ESR and CRP correlated
well both in aortitis (p < 0.05) and in periaortitis (p < 0.05). In periaortitis,
perfusion parameters agreed well with ESR and CRP values (p < 0.05) only in
untreated patients. CONCLUSION: Perfusion CT parameters in untreated aortitis and
chronic periaortitis correlate well with serological markers with respect to
disease activity assessment. However, in treated periaortitis, correlations were
weak, suggesting an increased role for (perfusion-based) imaging. ADVANCES IN
KNOWLEDGE: Volume perfusion CT may be used for diagnosis of
aortitis/periaortitis.
PMID- 26423600
TI - Prepregnancy Body Mass Index and Gestational Weight Gain Have No Negative Impact
on Maternal or Neonatal Iron Status.
AB - OBJECTIVE: To assess the impact of maternal obesity and excessive gestational
weight gain (GWG) on maternal and neonatal iron status and to explore the
possible mediating role of inflammation on hepcidin. METHODS: This analysis
included 230 pregnant adolescents (13-18 years) enrolled in either a longitudinal
or a cross-sectional study. Prepregnancy body mass index (ppBMI) and GWG were
obtained from medical records. Maternal iron status (hemoglobin, serum iron,
ferritin, transferrin receptor, total body iron, and hepcidin) and inflammation
(interleukin-6 [IL-6] and leptin) were assessed at midgestation (26.2 +/- 3.3
weeks) in the longitudinal cohort and at delivery (39.8 +/- 1.3 weeks) in both
study cohorts. Cord blood was collected in both studies and analyzed for iron
indicators. RESULTS: Approximately 40% of the adolescents entered pregnancy
overweight or obese. Multivariate analysis identified ppBMI as a negative
predictor of serum iron at midgestation (P = .009) and a positive predictor of
serum hepcidin at delivery (P = .02). None of the other maternal iron status
indicators were significantly associated with ppBMI or GWG. Serum IL-6 was
significantly positively associated with hepcidin at delivery (P = .0001) but not
at midgestation. There was a positive relationship between ppBMI and cord
hemoglobin (P = .03). CONCLUSION: These results suggest that adiposity-related
inflammation does not override the iron-mediated signals that regulate hepcidin
production during pregnancy, and in this adolescent cohort, there is no strong
evidence for a detrimental effect of maternal obesity and excessive weight gain
on iron status in the offspring at birth.
PMID- 26423601
TI - Proteoglycans in Leiomyoma and Normal Myometrium: Abundance, Steroid Hormone
Control, and Implications for Pathophysiology.
AB - Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth
muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan
composition of the leiomyoma ECM is thought to affect pathophysiology of the
disease. To test this hypothesis, we examined the abundance (by immunoblotting)
and expression (by quantitative real-time polymerase chain reaction) of the
proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium
and determined whether expression is affected by steroid hormones and menstrual
phase. Leiomyoma and normal myometrium were collected from women (n = 17)
undergoing hysterectomy or myomectomy. In vitro studies were performed on
immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and
without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of
decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower,
respectively, compared with normal myometrium. Abundance of versican mRNA was not
different between matched samples, whereas versican protein was increased 1.8
fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in
secretory phase leiomyoma compared with proliferative phase tissue. In UtLM
cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower
decorin expression in leiomyoma compared with myometrium may contribute to
disease growth and progression. As decorin inhibits the activity of specific
growth factors, its reduced level in the leiomyoma cell microenvironment may
promote cell proliferation and ECM deposition. Our data suggest that decorin
expression in leiomyoma is inhibited by progesterone, which may be a mechanism by
which the ovarian steroids affect leiomyoma growth and disease progression.
PMID- 26423602
TI - Afatinib, an irreversible ErbB family blocker, with protracted temozolomide in
recurrent glioblastoma: a case report.
AB - There are few effective treatments for recurrent glioblastoma multiforme (GBM).
We present a patient with recurrent GBM who achieved a prolonged response to
treatment with afatinib, an irreversible ErbB family blocker, plus temozolomide.
A 58-year-old female patient was diagnosed with multifocal primary GBM. After
surgical resection, first-line therapy comprised radiotherapy and temozolomide.
Following disease progression after 3 temozolomide cycles, the patient entered a
phase I/II clinical trial of afatinib (20-40 mg daily for 28 days) plus
temozolomide (50 mg/m2 every 21/28 days). Next-generation sequencing analysis of
the brain tumor specimen was performed. At the last assessment, 63 treatment
cycles had been completed and the patient had survived for ~5 years since
recurrence. Significant disease regression was observed after 5 cycles and was
maintained during long-term follow-up. Adverse events were consistent with the
known tolerability profile of afatinib and were managed by treatment
interruption/dose reduction. The patient had several epidermal growth factor
receptor (EGFR) aberrations, including gene amplification and EGFRvIII
positivity. Three somatic mutations were identified, including an unprecedented
extracellular-domain substitution (D247Y). The patient has survived ~6-fold
longer than normally expected in patients with recurrent GBM. The complex EGFR
genotype may underlie sustained response to afatinib plus temozolomide.
PMID- 26423603
TI - Decline of gustatory sensitivity with the progression of Alzheimer's disease.
AB - BACKGROUND: Patients with Alzheimer's disease (AD) manifest various impairments
in eating behavior. However, few previous studies have directly investigated the
gustatory function of AD patients, and results have been inconsistent. METHODS:
Thirty-two AD patients (Clinical Dementia Rating (CDR) 0.5/1/2, respectively
11/15/6 patients) and 22 normal control participants were examined to measure
detection and recognition thresholds of the four elemental tastes (sweet, salty,
sour, and bitter), and their ability to discriminate between tastes. Effects of
demographic and clinical factors (age, sex, histories of alcohol and tobacco
consumption, and CDR grade) on gustatory threshold were examined using ordinal
logistic regression analysis. Performance was compared between AD and control
groups. RESULTS: Total threshold values (the sum of threshold grades for the four
tastes) for detection and recognition of tastes were significantly higher in the
AD group. Detection thresholds for sweet, salty, and bitter, and recognition
thresholds for sweet and sour, were also significantly higher in the AD group.
Ordinal logistic regression analysis revealed that CDR grade was the only factor
that significantly affected both total threshold values. Regarding taste
discrimination, there were no significant differences between the AD group and
control group. CONCLUSIONS: These findings suggest that progression of dementia
severity accompanies gustatory decline. Although it seemingly paradoxical, weight
loss and preference for sweet tastes are frequently, often simultaneously,
observed in AD. Gustatory dysfunction may be partially involved in these
symptoms. Thus, the nutritional care of patients with AD could be improved by
making the taste of meals stronger, while controlling calorie and mineral intake.
PMID- 26423605
TI - Health care disparities among persons with comorbid schizophrenia and
cardiovascular disease: a case-control epidemiological study.
AB - AIMS: Studies showed health care disparities among persons with comorbid
schizophrenia and cardiovascular disease (CVD), including in countries with
universal health care. However, the potential positive effect of specific mental
health legislation has not been reported. This study aimed to investigate the
health care of persons with comorbid schizophrenia and CVD in a country with both
a national health insurance and a comprehensive rehabilitation law for persons
with mental disabilities. METHOD: This study builds on a large case-control
epidemiological sample (N = 52 189) of service users. Within the sample we
identified a sub-group of persons with CVD diagnoses (n = 8208) and compared
service users with and without schizophrenia on drug utilisation, laboratory
tests, visits to specialists and surgical interventions. RESULTS: Service users
with schizophrenia were less likely to meet similar indexes of care as their
counterparts: 91% cholesterol tests (p < 0.001), 60% stress tests (p < 0.001),
93% visits to specialists (p = 0.001), 93% drug utilisation (p < 0.001) and 55%
CVD surgical interventions (odds ratio 0.55, 95% confidence intervals 0.49-0.61).
CONCLUSIONS: In Israel, a country with a national health insurance and a
rehabilitation law specific for persons with mental disabilities, service users
with schizophrenia still fail to receive equitable levels of health care for CVD.
However, the disparities appear to be smaller than in other countries with
universal health insurance.
PMID- 26423604
TI - Distinct preoptic-BST nuclei dissociate paternal and infanticidal behavior in
mice.
AB - Paternal behavior is not innate but arises through social experience. After
mating and becoming fathers, male mice change their behavior toward pups from
infanticide to paternal care. However, the precise brain areas and circuit
mechanisms connecting these social behaviors are largely unknown. Here we
demonstrated that the c-Fos expression pattern in the four nuclei of the preoptic
bed nuclei of stria terminalis (BST) region could robustly discriminate five
kinds of previous social behavior of male mice (parenting, infanticide, mating,
inter-male aggression, solitary control). Specifically, neuronal activation in
the central part of the medial preoptic area (cMPOA) and rhomboid nucleus of the
BST (BSTrh) retroactively detected paternal and infanticidal motivation with more
than 95% accuracy. Moreover, cMPOA lesions switched behavior in fathers from
paternal to infanticidal, while BSTrh lesions inhibited infanticide in virgin
males. The projections from cMPOA to BSTrh were largely GABAergic. Optogenetic or
pharmacogenetic activation of cMPOA attenuated infanticide in virgin males. Taken
together, this study identifies the preoptic-BST nuclei underlying social
motivations in male mice and reveals unexpected complexity in the circuit
connecting these nuclei.
PMID- 26423606
TI - Dynamical modeling of uncertain interaction-based genomic networks.
AB - BACKGROUND: Most dynamical models for genomic networks are built upon two current
methodologies, one process-based and the other based on Boolean-type networks.
Both are problematic when it comes to experimental design purposes in the
laboratory. The first approach requires a comprehensive knowledge of the
parameters involved in all biological processes a priori, whereas the results
from the second method may not have a biological correspondence and thus cannot
be tested in the laboratory. Moreover, the current methods cannot readily utilize
existing curated knowledge databases and do not consider uncertainty in the
knowledge. Therefore, a new methodology is needed that can generate a dynamical
model based on available biological data, assuming uncertainty, while the results
from experimental design can be examined in the laboratory. RESULTS: We propose a
new methodology for dynamical modeling of genomic networks that can utilize the
interaction knowledge provided in public databases. The model assigns discrete
states for physical entities, sets priorities among interactions based on
information provided in the database, and updates each interaction based on
associated node states. Whenever uncertainty in dynamics arises, it explores all
possible outcomes. By using the proposed model, biologists can study regulation
networks that are too complex for manual analysis. CONCLUSIONS: The proposed
approach can be effectively used for constructing dynamical models of interaction
based genomic networks without requiring a complete knowledge of all parameters
affecting the network dynamics, and thus based on a small set of available data.
PMID- 26423608
TI - Large spin Hall magnetoresistance and its correlation to the spin-orbit torque in
W/CoFeB/MgO structures.
AB - The phenomena based on spin-orbit interaction in heavy metal/ferromagnet/oxide
structures have been investigated extensively due to their applicability to the
manipulation of the magnetization direction via the in-plane current. This
implies the existence of an inverse effect, in which the conductivity in such
structures should depend on the magnetization orientation. In this work, we
report a systematic study of the magnetoresistance (MR) of W/CoFeB/MgO structures
and its correlation with the current-induced torque to the magnetization. We
observe that the MR is independent of the angle between the magnetization and
current direction but is determined by the relative magnetization orientation
with respect to the spin direction accumulated by the spin Hall effect, for which
the symmetry is identical to that of so-called the spin Hall magnetoresistance.
The MR of ~1% in W/CoFeB/MgO samples is considerably larger than those in other
structures of Ta/CoFeB/MgO or Pt/Co/AlOx, which indicates a larger spin Hall
angle of W. Moreover, the similar W thickness dependence of the MR and the
current-induced magnetization switching efficiency demonstrates that MR in a non
magnet/ferromagnet structure can be utilized to understand other closely
correlated spin-orbit coupling effects such as the inverse spin Hall effect or
the spin-orbit spin transfer torques.
PMID- 26423607
TI - Non-invasive imaging and cellular tracking of pulmonary emboli by near-infrared
fluorescence and positron-emission tomography.
AB - Functional imaging of proteolytic activity is an emerging strategy to quantify
disease and response to therapy at the molecular level. We present a new peptide
based imaging probe technology that advances these goals by exploiting enzymatic
activity to deposit probes labelled with near-infrared (NIR) fluorophores or
radioisotopes in cell membranes of disease-associated proteolysis. This strategy
allows for non-invasive detection of protease activity in vivo and ex vivo by
tracking deposited probes in tissues. We demonstrate non-invasive detection of
thrombin generation in a murine model of pulmonary embolism using our protease
activated peptide probes in microscopic clots within the lungs with NIR
fluorescence optical imaging and positron-emission tomography. Thrombin activity
is imaged deep in tissue and tracked predominantly to platelets within the lumen
of blood vessels. The modular design of our probes allows for facile
investigation of other proteases, and their contributions to disease by tailoring
the protease activation and cell-binding elements.
PMID- 26423609
TI - Azo-Based Iridium(III) Complexes as Multicolor Phosphorescent Probes to Detect
Hypoxia in 3D Multicellular Tumor Spheroids.
AB - Hypoxia is an important characteristic of malignant solid tumors and is
considered as a possible causative factor for serious resistance to chemo- and
radiotherapy. The exploration of novel fluorescent probes capable of detecting
hypoxia in solid tumors will aid tumor diagnosis and treatment. In this study, we
reported the design and synthesis of a series of "off-on" phosphorescence probes
for hypoxia detection in adherent and three-dimensional multicellular spheroid
models. All of the iridium(III) complexes incorporate an azo group as an azo
reductase reactive moiety to detect hypoxia. Reduction of non-phosphorescent
probes Ir1-Ir8 by reductases under hypoxic conditions resulted in the generation
of highly phosphorescent corresponding amines for detection of hypoxic regions.
Moreover, these probes can penetrate into 3D multicellular spheroids over 100 MUm
and image the hypoxic regions. Most importantly, these probes display a high
selectivity for the detection of hypoxia in 2D cells and 3D multicellular
spheroids.
PMID- 26423610
TI - Stroboscopic phenomena in superconductors with dynamic pinning landscape.
AB - Introducing artificial pinning centers is a well established strategy to trap
quantum vortices and increase the maximal magnetic field and applied electric
current that a superconductor can sustain without dissipation. In case of
spatially periodic pinning, a clear enhancement of the superconducting critical
current arises when commensurability between the vortex configurations and the
pinning landscape occurs. With recent achievements in (ultrafast) optics and
nanoengineered plasmonics it has become possible to exploit the interaction of
light with superconductivity, and create not only spatially periodic imprints on
the superconducting condensate, but also temporally periodic ones. Here we show
that in the latter case, temporal matching phenomena develop, caused by
stroboscopic commensurability between the characteristic frequency of the vortex
motion under applied current and the frequency of the dynamic pinning. The
matching resonances persist in a broad parameter space, including magnetic field,
driving current, or material purity, giving rise to unusual features such as
externally variable resistance/impedance and Shapiro steps in current-voltage
characteristics. All features are tunable by the frequency of the dynamic pinning
landscape. These findings open further exploration avenues for using flashing,
spatially engineered, and/or mobile excitations on superconductors, permitting us
to achieve advanced functionalities.
PMID- 26423611
TI - Epirubicin-gold nanoparticles suppress hepatocellular carcinoma xenograft growth
in nude mice.
AB - We sought to investigate the effects of epirubicin-nanogold compounds (EPI-AuNP)
on hepatocellular carcinoma xenograft growth in nude mice. EPI-AuNP was prepared
and hepatoma xenograft model was established in nude mice. The mice were then
randomly divided into four groups: the control group with injection of saline,
the AuNP treatment group, the EPI treatment group and the EPI-AuNP treatment
group. After two weeks, the hepatoma weight and volume of the xenografts were
assessed. Our transmission electron microscopy revealed that epirubicin-gold
nanoparticles caused significantly more structural changes of hepatocellular
carcinoma cells HepG2. The tumor weight in the Epi-AuNP treatment group (0.80+/
0.11g) was significantly lower than that of the control group (2.48+/-0.15 g),
the AuNP treatment group (1.67+/-0.17 g), and the EPI treatment group (1.39+/
0.10g) (P<0.01). Furthermore, the tumor volume of mice in the EPI-AuNP treatment
group (0.27+/-0.06 cm3) was significantly smaller than that of the control group
(2.23+/-0.34 cm3), the AuNP treatment group (1.21+/-0.25 cm3) and the EPI
treatment group (0.81+/-0.11 cm3) (P<0.01). In conclusion, epirubicin-nanogold
compounds (EPI-AuNP) have significant inhibitory effects on the growth of
hepatocellular carcinoma cells in vivo.
PMID- 26423612
TI - Generation of monoclonal antibodies against n-3 fatty acid desaturase.
PMID- 26423613
TI - Retinol binding protein 4 correlates with and is an early predictor of carotid
atherosclerosis in type 2 diabetes mellitus patients.
AB - The association of retinol binding protein 4 (RBP4) with atherosclerosis of the
carotid artery in type 2 diabetes mellitus (T2DM) remains undefined. We aimed to
investigate the correlation of RBP4 expression with atherosclerosis of the
carotid artery in T2DM. A total of 1,076 subjects were investigated for intima
media thickness of the bilateral common carotid arteries, and they were divided
into three groups: in group I, patients had normal neck vascular ultrasound, in
group II, intimal carotid artery media thickness was equal to or more than 1 mm,
and in group III, carotid artery plaque was present. Height, weight, blood
pressure (BP), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), total
cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C),
high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (Apo A-1),
apolipoprotein B (Apo B) and lipoprotein (a) (Lp(a)) were determined by routine
laboratory methods. RBP4 and high sensitivity C reactive protein (HsCRP) were
measured by an enzyme-linked immuno-sorbent assay, and insulin concentration was
measured by an electrochemiluminescence sandwich immunoassay. Duration of
diabetes, waist and BP, FPG, HbA1c, TG, TC, LDL-C, APOB, Lp(a), HsCRP, RBP4 and
homeostasis model assessment insulin resistance index (HOMA-IR) were
significantly lower in group I than in the other two groups (P<0.01, P<0.01).
Plasma levels of HbA1c, RBP4, LDL-C, TC, HOMA-IR, HsCRP and Lp(a), waist and BP
were significantly increased in group III than in group II (P<0.01). Multivariate
logistic regression analysis showed that there were seven factors associated with
the occurrence of carotid artery atherosclerosis and its risks in descending
order were: high LDL-C, high waist, high HsCRP, duration of diabetes, high HOMA
IR, HbA1c and high RBP4. Our finding supported that RBP4 was positively
correlated with carotid atherosclerosis in patients with T2DM and could be used
as an early predictor of cardiovascular disease.
PMID- 26423614
TI - Scaphoid fracture non-union: a systematic review of surgical treatment using bone
graft.
AB - This systematic review assesses the quality and outcomes of published articles
concerning bone graft surgery for scaphoid fracture non-union. Searches of the
CENTRAL, MEDLINE, EMBASE, CINAHL and AMED databases captured 2710 articles. Each
article was screened and 144 met our inclusion criteria. Data regarding source,
study design, population, intervention, comparator and outcomes were extracted.
There were 5464 scaphoid non-union outcomes within the 144 studies. Mean reported
union rates for vascularized and non-vascularized bone graft were 84% and 80%,
respectively. Avascular necrosis was diagnosed in several ways and, when present,
the vascularized bone graft union rate was 74% compared with 62% with non
vascularized bone graft. Reported union rates vary considerably. These
differences may be due to patient factors, fracture factors, treatment factors or
study design failures or bias. We recommend that future researchers take into
account the deficiencies of previous studies and use the suggested minimum data
set in future studies. LEVEL OF EVIDENCE: II.
PMID- 26423615
TI - Peritoneal tuberculosis presenting with portal vein thrombosis and transudative
Ascites - a diagnostic dilemma: case report.
AB - BACKGROUND: Peritoneal tuberculosis is an important problem in regions of the
world where tuberculosis is still prevalent (Chest 1991; 99:1134). Atypical
presentations such as portal vein thrombosis can delay diagnosis or result in
misdiagnosis (Gut 1990; 31:1130, Acta ClinBelg 2012; 67(2):137-9, J Cytol Histol
2014; 5:278, Digestive Diseases and Sciences 1991; 36(1):112-115). A high index
of suspicion is required for the diagnosis of peritoneal tuberculosis, as the
analysis of peritoneal fluid for tuberculous bacillus is often ineffective, and
may increase mortality due to delayed diagnosis. (Clin Effect Dis 2002;35: 409
13) In light of new evidence, peritoneal biopsy through laparoscopy or laparotomy
has emerged as the gold standard for diagnosis (Clin Effect Dis 2002; 35: 409
13). CASE PRESENTATION: We report a case of a 35 year old Sri Lankan female
employed in a Middle - Eastern country who presented with progressive abdominal
distention and constitutional symptoms for four months duration. She had been
investigated abroad and diagnosed with ascites with chronic portal vein
thrombosis following which warfarin therapy had been commenced suspecting an
underlying thrombophilia. Despite treatment her symptoms had worsened. Therefore
she had decided to return to Sri Lanka for further evaluation. After ruling out
inherited thrombophilic states and the antiphospholipid syndrome, further
investigations revealed a transudative ascites and high inflammatory markers. The
tuberculosis work up on peritoneal fluid was negative. Therefore, we proceeded
with laparoscopy which showed multiple nodular deposits on abdominal wall, bowel
and omentum and peritoneal biopsy revealed granulomatous inflammation with
caseous type necrosis compatible with mycobacterium tuberculosis infection. This
was confirmed by tuberculosis genome identification on the biopsy sample
confirming a diagnosis of peritoneal tuberculosis with secondary portal vein
thrombosis and cavernous formation due to local inflammation. The patient was
started on anti-tuberculosis treatment and warfarin was discontinued, following
which she made a remarkable recovery. CONCLUSION: Peritoneal tuberculosis can
present with unusual manifestations such as portal vein thrombosis and
transudative ascites causing a diagnostic dilemma. Ascitic fluid analysis is
generally not diagnostic. Under such circumstances peritoneal biopsy should be
performed as it has a good diagnostic yield and accuracy.
PMID- 26423616
TI - Semantic biomedical resource discovery: a Natural Language Processing framework.
AB - BACKGROUND: A plethora of publicly available biomedical resources do currently
exist and are constantly increasing at a fast rate. In parallel, specialized
repositories are been developed, indexing numerous clinical and biomedical tools.
The main drawback of such repositories is the difficulty in locating appropriate
resources for a clinical or biomedical decision task, especially for non
Information Technology expert users. In parallel, although NLP research in the
clinical domain has been active since the 1960s, progress in the development of
NLP applications has been slow and lags behind progress in the general NLP
domain. The aim of the present study is to investigate the use of semantics for
biomedical resources annotation with domain specific ontologies and exploit
Natural Language Processing methods in empowering the non-Information Technology
expert users to efficiently search for biomedical resources using natural
language. METHODS: A Natural Language Processing engine which can "translate"
free text into targeted queries, automatically transforming a clinical research
question into a request description that contains only terms of ontologies, has
been implemented. The implementation is based on information extraction
techniques for text in natural language, guided by integrated ontologies.
Furthermore, knowledge from robust text mining methods has been incorporated to
map descriptions into suitable domain ontologies in order to ensure that the
biomedical resources descriptions are domain oriented and enhance the accuracy of
services discovery. The framework is freely available as a web application at (
http://calchas.ics.forth.gr/ ). RESULTS: For our experiments, a range of clinical
questions were established based on descriptions of clinical trials from the
ClinicalTrials.gov registry as well as recommendations from clinicians. Domain
experts manually identified the available tools in a tools repository which are
suitable for addressing the clinical questions at hand, either individually or as
a set of tools forming a computational pipeline. The results were compared with
those obtained from an automated discovery of candidate biomedical tools. For the
evaluation of the results, precision and recall measurements were used. Our
results indicate that the proposed framework has a high precision and low recall,
implying that the system returns essentially more relevant results than
irrelevant. CONCLUSIONS: There are adequate biomedical ontologies already
available, sufficiency of existing NLP tools and quality of biomedical annotation
systems for the implementation of a biomedical resources discovery framework,
based on the semantic annotation of resources and the use on NLP techniques. The
results of the present study demonstrate the clinical utility of the application
of the proposed framework which aims to bridge the gap between clinical question
in natural language and efficient dynamic biomedical resources discovery.
PMID- 26423617
TI - A randomised controlled trial comparing the effects of a 12-week supervised
exercise versus usual care on outcomes in haematological cancer patients.
AB - PURPOSE: Following treatment, haematological cancer (HEM) patients exhibit
significant physical deconditioning and psychological distress. Exercise has been
shown as a clinically effective and safe intervention for cancer patients, with
the potential to reverse the deleterious effects following treatment. Our aim was
to investigate the efficacy of a 12-week exercise rehabilitation on cancer
related fatigue (CRF) and associated outcomes in HEM patients post-treatment.
METHODS: Patients with a HEM were recruited to participate in a 12-week exercise
rehabilitation intervention post-treatment. Pre-, post- and follow-up assessments
were conducted on outcome measures including CRF, quality of life (QoL),
psychological distress, cardiovascular fitness, muscle strength (MS) and body
composition. Patients were given tailored exercise programmes comprising aerobic
and resistance exercises, carried out three times per week for 12 weeks in local
gyms and clinics. Usual-care participants were offered a delayed, tailored 12
week exercise intervention after the initial study period. RESULTS: Thirty-seven
patients (49 % recruitment rate) were randomly assigned to the 12-week exercise
rehabilitation (n = 18) or usual care (n = 19) with a 91 % adherence to the
exercise intervention. Following the exercise programme, significant improvements
were seen in CRF (p = 0.01), cardiovascular fitness (p <= 0.001), QoL (p <=
0.001), MS (p <= 0.001) and body composition (p = 0.001), with moderate to large
effects for all primary outcomes. Patient follow-up at 24 weeks demonstrated
outcome maintenance in the exercise rehabilitation group and significant
improvements in outcomes in usual-care patients following participation in a
delayed exercise programme. There were no adverse reactions or study withdrawals.
CONCLUSIONS: A 12-week exercise rehabilitation programme resulted in significant
statistical (p <= 0.05) and clinical improvements in CRF and additional outcomes
in HEM patients following treatment. Additionally, a 12-week delayed exercise
programme showed similar significant improvements in patient outcomes. TRIAL
REGISTRATION: Australian New Zealand Clinical Trials Registry
ACTRN12609000450213.
PMID- 26423620
TI - Special Collection: Emerging Concepts in Three-Dimensional Microtissues.
AB - Over the past decade, the concept of tissue engineering has been extended to
include technologies that use multicellular aggregates, not only to repair or
replace tissue but also as a stand-alone in vitro device (e.g., "organ-on-a
chip") with well-defined biological outputs. The advantage of such systems is
that they allow for culture of one or more cell types in three dimensions, which
may promote tissue function that is more mimetic of the in vivo state, while
allowing high-throughput sample testing and a large degree of control of external
culture factors that may lead to more reproducible results than that found in the
more complex in vivo environment. While the means used to achieve these devices
vary greatly, in this special collection, we focus our attention on formation and
use of scaffold-free cellular aggregates (three-dimensional microtissues).
PMID- 26423618
TI - A randomized, multicenter, phase II/III study to determine the optimal dose and
to evaluate the efficacy and safety of pegteograstim (GCPGC) on chemotherapy
induced neutropenia compared to pegfilgrastim in breast cancer patients: KCSG
PC10-09.
AB - PURPOSE: Pegylated granulocyte-colony-stimulating factor (G-CSF) is frequently
used to prevent febrile neutropenia (FN) in patients undergoing chemotherapy with
a high risk of myelosuppression. This phase II/III study was conducted to
determine the adequate dose of pegteograstim, a new formulation of pegylated G
CSF, and to evaluate the efficacy and safety of pegteograstim compared to
pegfilgrastim. METHODS: In the phase II part, 60 breast cancer patients who were
undergoing DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and
cyclophosphamide) chemotherapy were randomly selected to receive a single
subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each
chemotherapy cycle. The phase III part was seamlessly started to compare the dose
of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast
cancer patients. The primary endpoint of both the phase II and III parts was the
duration of grade 4 neutropenia in the chemotherapy cycle 1. RESULTS: The mean
duration of grade 4 neutropenia for the 3.6 mg pegteograstim (n = 33) was similar
to that for the 6.0 mg pegteograstim (n = 26) (1.97 +/- 1.79 days vs. 1.54 +/-
0.95 days, p = 0.33). The 6.0 mg pegteograstim was selected to be compared with
the 6.0 mg pegfilgrastim in the phase III part. In the phase III part, the
primary analysis revealed that the efficacy of pegteograstim (n = 56) was non
inferior to that of pegfilgrastim (n = 59) [duration of grade 4 neutropenia, 1.64
+/- 1.18 days vs. 1.80 +/- 1.05 days; difference, -0.15 +/- 1.11 (p = 0.36, 97.5
% confidence intervals = 0.57 and 0.26)]. The time to the absolute neutrophil
count (ANC) recovery of pegteograstim (>=2000/MUL) was significantly shorter than
that of pegfilgrastim (8.85 +/- 1.45 days vs. 9.83 +/- 1.20 days, p < 0.0001).
Other secondary endpoints showed no significant difference between the two
groups. The safety profiles of the two groups did not differ significantly.
CONCLUSIONS: Pegteograstim was shown to be as effective as pegfilgrastim in the
reduction of chemotherapy-induced neutropenia in the breast cancer patients who
were undergoing chemotherapy with a high risk of myelosuppression.
PMID- 26423619
TI - Linking individual medicare health claims data with work-life claims and other
administrative data.
AB - BACKGROUND: Researchers investigating health outcomes for populations over age 65
can utilize Medicare claims data, but these data include no direct information
about individuals' health prior to age 65 and are not typically linkable to files
containing data on exposures and behaviors during their worklives. The current
paper is a proof-of-concept, of merging employers' administrative data and
private, employment-based health claims with Medicare data. Characteristics of
the linked data, including sensitivity and specificity, are evaluated with an eye
toward potential uses of such linked data. This paper uses a sample of former
manufacturing workers from an industrial cohort as a test case. The dataset
created by this integration could be useful to research in areas such as social
epidemiology and occupational health. METHODS: Medicare and employment
administrative data were linked for a large cohort of manufacturing workers
(employed at some point during 1996-2008) who transitioned onto Medicare between
2001-2009. Data on work-life health, including biometric indicators, were used to
predict health at age 65 and to investigate the concordance of employment-based
insurance claims with subsequent Medicare insurance claims. RESULTS: Chronic
diseases were found to have relatively high levels of concordance between
employment-based private insurance and subsequent Medicare insurance. Information
about patient health prior to receipt of Medicare, including biometric
indicators, were found to predict health at age 65. CONCLUSIONS: Combining these
data allows for evaluation of continuous health trajectories, as well as modeling
later-life health as a function of work-life behaviors and exposures. It also
provides a potential endpoint for occupational health research. This is the first
harmonization of its kind, providing a proof-of-concept. The dataset created by
this integration could be useful for research in areas such as social
epidemiology and occupational health.
PMID- 26423621
TI - Establishing assay sensitivity in QT studies: experience with the use of
moxifloxacin in an early phase clinical pharmacology study and comparison with
its effect in a thorough QT study.
AB - OBJECTIVE: To compare the effect of moxifloxacin as a positive control in a
single ascending dose (SAD) study with that in a thorough QT (TQT) study.
METHODS: Moxifloxacin was used as a positive control in a SAD study and a TQT
study during the evaluation of the QT liability of a new drug. The SAD study had
enrolled 24 males and the TQT study 25 males. Both studies intensively monitored
electrocardiograms (ECGs) and pharmacokinetic sampling. Effect of moxifloxacin on
QTc interval was analysed in each study by intersection union test (IUT) and by
exposure-response (ER) analysis and the results compared. Cost-effectiveness of
this approach was computed. RESULTS: Analysis by IUT revealed that the maximum
mean (90 % confidence interval (CI)) placebo-corrected change from baseline
(DeltaDeltaQTcF) in the SAD study and the TQT study were remarkably similar (10.7
(6.5; 14.9) ms vs. 9.09 (6.20; 11.98) ms, respectively). In both studies, assay
sensitivity was established by the 90 % lower bound exceeding 5 ms. ER analysis
revealed the slopes in both studies to be significantly different from zero and
comparable. Bootstrap-predicted effects of moxifloxacin at geometric mean
concentrations of ~3000 ng/mL were 8.19 (90 % CI 5.86; 10.7) ms in the SAD study
and 7.33 (90 % CI 5.69; 9.70) ms in the TQT study. CONCLUSION: Moxifloxacin can
be integrated effectively in a SAD study to establish assay sensitivity, and a
TQT study may be replaced by a SAD study which has the required assay
sensitivity. Further experience is warranted to verify this conclusion.
PMID- 26423623
TI - Pulsed amperometric detection at glassy carbon electrodes: A new waveform for
sensitive and reproducible determination of electroactive compounds.
AB - In this work, the application of a new pulsed amperometric detection (PAD)
waveform at a glassy carbon electrode, operating in typical chromatographic
mobile phases, is proposed for the sensitive and reproducible determination of
arylethanolaminic and phenolic moiety based compounds (e.g. beta-agonists and
polyphenols). Preliminary experiments by cyclic voltammetry were carried out to
investigate the electrochemical behaviour and to select the detection and
cleaning electrode potentials. The proposed potential-time profile was designed
to prevent the carbon electrode fouling under repeated analyses, thus ensuring a
reproducible and sensitive quantitative determination, without the need of any
mechanical or chemical electrode cleaning procedure. The waveform electrochemical
parameters, including detection and delay times, were optimized in terms of
sensitivity, limit of detection and response stability. The optimized waveform
allowed the sensitive and stable detection of model compounds, such as
clenbuterol and caffeic acid, that showed detection limits of 0.1 MUg L(-1) and
14 MUg L(-1), quantification limits of 0.4 MUg L(-1) and 46 MUg L(-1), and
linearity up to 100 MUg L(-1) (r = 0.9993) and 10 mg L(-1) (r = 0.9998),
respectively. Similar results were obtained for other compounds of the same
classes, with precision values under repeatability conditions ranging from 3.0 to
5.9%. The proposed method can be then considered as an excellent alternative to
the post-column detection of beta-agonists, phenols and polyphenols.
PMID- 26423624
TI - Inductively coupled plasma - Tandem mass spectrometry (ICP-MS/MS): A powerful and
universal tool for the interference-free determination of (ultra)trace elements -
A tutorial review.
AB - This paper is intended as a tutorial review on the use of inductively coupled
plasma - tandem mass spectrometry (ICP-MS/MS) for the interference-free
quantitative determination and isotope ratio analysis of metals and metalloids in
different sample types. Attention is devoted both to the instrumentation and to
some specific tools and procedures available for advanced method development.
Next to the more typical reaction gases, e.g., H2, O2 and NH3, also the use of
promising alternative gases, such as CH3F, is covered, and the possible reaction
pathways with those reactive gases are discussed. A variety of published
applications relying on the use of ICP-MS/MS are described, to illustrate the
added value of tandem mass spectrometry in (ultra)trace analysis.
PMID- 26423622
TI - Population pharmacokinetics of vancomycin in adult Chinese patients with post
craniotomy meningitis and its application in individualised dosage regimens.
AB - PURPOSE: Vancomycin (VCM) is a first-line antibacterial drug used to treat post
craniotomy meningitis (PCM). VCM pharmacokinetic parameters are altered in PCM
patients, compared to those in other patients. Although VCM population
pharmacokinetics (PPK) has been reported, changes in VCM PPK in adult Chinese PCM
patients remain unknown. We developed a VCM PPK model in adult Chinese PCM
patients and proposed a new strategy for individualising VCM administration using
this model. METHODS: Data was obtained from a prospective study of 100 adult PCM
patients in the Neurosurgery Department of the First Affiliated Hospital of
Fujian Medical University. The trough concentrations at steady state were
determined by enzyme multiplied immunoassay. Nonlinear mixed-effect model
software was employed to develop the PPK model. The final model was evaluated
using the bootstrap method and normalised prediction error distribution and
through the testing of 20 independent adult PCM patients. RESULTS: VCM clearance
in PCM patients was higher than that observed in other patients. Creatinine
clearance affected VCM clearance, whereas no co-administered drugs influenced VCM
pharmacokinetics. Trough concentrations were accurately predicted by the final
model, while the prediction errors were less than +/-32 %. Moreover, a new
strategy for individualising VCM regimens using the PPK model was proposed and
validated. CONCLUSIONS: A PPK model was developed to estimate the individual
clearance in inpatients receiving intravenously infused VCM and could be used to
develop individualised dosing of adult Chinese PCM patients.
PMID- 26423625
TI - Methods for the experimental characterization and analysis of the efficiency and
speed of chromatographic columns: A step-by-step tutorial.
AB - Due to the developing insights in the theory of chromatography, column
manufacturers of any kind (industrial, academic) nowadays have a broad array of
experimental column testing tools at their disposal. The present tutorial aims at
helping the novice in the field getting an overview of these tools and provides a
fixed procedure to carry out the subsequent steps in the column quality analysis
(guided via an Excel template file). After some brief introduction about the main
equations, the reader is taken step by step through the theories underlying the
measurement methods for the different column and performance parameters. In the
final section, the reader is taken through the different items in the Excel
template.
PMID- 26423626
TI - Automated on-line liquid-liquid extraction system for temporal mass spectrometric
analysis of dynamic samples.
AB - Most real samples cannot directly be infused to mass spectrometers because they
could contaminate delicate parts of ion source and guides, or cause ion
suppression. Conventional sample preparation procedures limit temporal resolution
of analysis. We have developed an automated liquid-liquid extraction system that
enables unsupervised repetitive treatment of dynamic samples and instantaneous
analysis by mass spectrometry (MS). It incorporates inexpensive open-source
microcontroller boards (Arduino and Netduino) to guide the extraction and
analysis process. Duration of every extraction cycle is 17 min. The system
enables monitoring of dynamic processes over many hours. The extracts are
automatically transferred to the ion source incorporating a Venturi pump.
Operation of the device has been characterized (repeatability, RSD = 15%, n = 20;
concentration range for ibuprofen, 0.053-2.000 mM; LOD for ibuprofen, ~0.005 mM;
including extraction and detection). To exemplify its usefulness in real-world
applications, we implemented this device in chemical profiling of pharmaceutical
formulation dissolution process. Temporal dissolution profiles of commercial
ibuprofen and acetaminophen tablets were recorded during 10 h. The extraction-MS
datasets were fitted with exponential functions to characterize the rates of
release of the main and auxiliary ingredients (e.g. ibuprofen, k = 0.43 +/- 0.01
h(-1)). The electronic control unit of this system interacts with the operator
via touch screen, internet, voice, and short text messages sent to the mobile
phone, which is helpful when launching long-term (e.g. overnight) measurements.
Due to these interactive features, the platform brings the concept of the
Internet-of-Things (IoT) to the chemistry laboratory environment.
PMID- 26423627
TI - A strategy for fast screening and identification of sulfur derivatives in
medicinal Pueraria species based on the fine isotopic pattern filtering method
using ultra-high-resolution mass spectrometry.
AB - Sulfurous compounds are commonly present in plants, fungi, and animals. Most of
them were reported to possess various bioactivities. Isotopic pattern filter
(IPF) is a powerful tool for screening compounds with distinct isotope pattern.
Over the past decades, the IPF was used mainly to study Cl- and Br-containing
compounds. To our knowledge, the algorithm was scarcely used to screen S
containing compounds, especially when combined with chromatography analyses,
because the (34)S isotopic ion is drastically affected by (13)C2 and (18)O. Thus,
we present a new method for a fine isotopic pattern filter (FIPF) based on the
separated M + 2 ions ((12)C(x)(1)H(y)(16)O(z)(32)S(13)C2(18)O,
(12)C(x+2)(1)H(y)(16)O(z+1)(34)S, tentatively named M + 2OC and M + 2S) with an
ultra-high-resolution mass (100,000 FWHM @ 400 m/z) to screen sulfur derivatives
in traditional Chinese medicines (TCM).This finer algorithm operates through
convenient filters, including an accurate mass shift of M + 2OC and M + 2S from M
and their relative intensity compared to M. The method was validated at various
mass resolutions, mass accuracies, and screening thresholds of flexible elemental
compositions. Using the established FIPF method, twelve S-derivatives were found
in the popular medicinal used Pueraria species, and 9 of them were tentatively
identified by high-resolution multiple stage mass spectrometry (HRMS(n)). The
compounds were used to evaluate the sulfurous compounds' situation in
commercially purchased Pueraria products. The strategy presented here provides a
promising application of the IPF method in a new field.
PMID- 26423628
TI - Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide
as short-term exposure biomarkers for evaluation of toxicokinetics in rats and
daily internal exposure in humans using isotope dilution ultra-high performance
liquid chromatography tandem mass spectrometry.
AB - Mercapturic acid metabolites from dietary acrylamide are important short-term
exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of
studies have focused on the measurement of two metabolites, N-acetyl-S-(2
carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L
cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary
metabolites cannot be fully understood. We developed an isotope dilution ultra
high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS)
method for the simultaneous determination of all four mercapturic acid adducts of
acrylamide and its primary metabolite glycidamide under the electroscopy
ionization negative (ESI-) mode in the present study. The limit of detection
(LOD) and limit of quantification (LOQ) of the analytes ranged 0.1-0.3 ng/mL and
0.4-1.0 ng/mL, respectively. The recovery rates with low, intermediate and high
spiking levels were calculated as 95.5%-105.4%, 98.2%-114.0% and 92.2%-108.9%,
respectively. Acceptable within-laboratory reproducibility (RSD<7.0%)
substantially supported the use of current method for robust analysis. Rapid
pretreatment procedures and short run time (8 min per sample) ensured good
efficiency of metabolism profiling, indicating a wide application for
investigating short-term internal exposure of dietary acrylamide. Our proposed
UHPLC-MS/MS method was successfully applied to the toxicokinetic study of
acrylamide in rats. Meanwhile, results of human urine analysis indicated that the
levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which
did not appear in the mercapturic acid metabolites in rodents, were more than the
sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA).
Thus, AAMA-sul may alternatively become a specific biomarker for investigating
the acrylamide exposure in humans. Current proposed method provides a substantial
methodology support for comprehensive profiling of toxicokinetics and daily
internal exposure evaluations of acrylamide in vivo.
PMID- 26423629
TI - Increase the accessibility and scale of targeted metabolomics: Construction of a
human urinary metabolome-wide multiple reaction monitoring library using directly
coupled reversed-phase and hydrophilic interaction chromatography.
AB - Multiple reaction monitoring (MRM) is wildly employed to research drug
absorption, distribution, metabolism, excretion and pharmacokinetics in
pharmaceutical and clinical laboratories. Recently, scientists in these areas
have shown great interest in utilization of metabolomics to evaluate drug
efficacy and toxicity. MRM-based targeted metabolomics is intrinsically more
sensitive and selective than MS based untargeted metabolomics in complex
biological samples. MRM also minimizes data complexity for fast and focused
analysis of core metabolites. Nevertheless, to mitigate the intrinsic targeted
nature of MRM and promote it as a discovery toolbox for metabolomics, larger
scale MRM assays providing more comprehensive biological information are highly
desirable. Here, we employed data-dependent and data-independent strategies to
perform extensive MS/MS mapping of human urinary metabolome with the assistance
of a directly-coupled reversed-phase liquid chromatography and hydrophilic
interaction chromatography (RPLC-HILIC) for simultaneous profiling of hydrophilic
and hydrophobic metabolites. RPLC-HILIC enables to save time, limit sample
consumption and facilitate data interpretation by removing data redundancy
occurring between separate RPLC and HILIC methods. Major product ions in the raw
MS/MS spectra were used to build a human urinary metabolome-wide MRM library
which contains 749 refined MRM tags in negative ion mode with 198 of them being
unambiguously or tentatively assigned for particular metabolites. The library
relieves researchers from the most time-consuming setup of massive MRM
transitions and making an important step toward large-scale targeted urinary
metabolomics.
PMID- 26423630
TI - Fiber array based hyperspectral Raman imaging for chemical selective analysis of
malaria-infected red blood cells.
AB - A new setup for Raman spectroscopic wide-field imaging is presented. It combines
the advantages of a fiber array based spectral translator with a tailor-made
laser illumination system for high-quality Raman chemical imaging of sensitive
biological samples. The Gaussian-like intensity distribution of the illuminating
laser beam is shaped by a square-core optical multimode fiber to a top-hat
profile with very homogeneous intensity distribution to fulfill the conditions of
Koehler. The 30 m long optical fiber and an additional vibrator efficiently
destroy the polarization and coherence of the illuminating light. This
homogeneous, incoherent illumination is an essential prerequisite for stable
quantitative imaging of complex biological samples. The fiber array translates
the two-dimensional lateral information of the Raman stray light into separated
spectral channels with very high contrast. The Raman image can be correlated with
a corresponding white light microscopic image of the sample. The new setup
enables simultaneous quantification of all Raman spectra across the whole spatial
area with very good spectral resolution and thus outperforms other Raman imaging
approaches based on scanning and tunable filters. The unique capabilities of the
setup for fast, gentle, sensitive, and selective chemical imaging of biological
samples were applied for automated hemozoin analysis. A special algorithm was
developed to generate Raman images based on the hemozoin distribution in red
blood cells without any influence from other Raman scattering. The new imaging
setup in combination with the robust algorithm provides a novel, elegant way for
chemical selective analysis of the malaria pigment hemozoin in early ring stages
of Plasmodium falciparum infected erythrocytes.
PMID- 26423631
TI - Fluorescence imaging for in situ detection of cell surface sialic acid by
competitive binding of 3-(dansylamino)phenylboronic acid.
AB - Sialic acid (SA) usually locates at the terminal position of the sugar chains on
cell membranes, and its expression level is closely associated with cancer. Here
polysialic acid (PSA) embedded gold nanoparticles (AuNPs) were prepared and
functionalized with fluorescent 3-(dansylamino)phenylboronic acid (DAPB) for in
situ imaging and detection of cell surface SA. The fluorescence resonance energy
transfer (FRET) from DAPB to AuNPs quenched the fluorescence of DAPB. In the
presence of additional SA or SA-abundant cells, the competitive binding of DAPB
with SA and PSA led to the release of the assembled DAPB from the surface of PSA
embedded AuNPs, resulting in fluorescence of DAPB on SA-abundant cell surface.
The proposed methods realized the in situ imaging and monitoring of cell surface
SA, and could also be applied to the quantification of cell number and the
amounts of cell surface SA. This work not only proposed a convenient
visualization method for the analysis of SA on cell membranes, but also provided
a potential tool for accelerating the elucidation of the basic role of SA in
various biological processes and development of anti-cancer therapies.
PMID- 26423632
TI - Risk assessment of agricultural pesticides in water, sediment, and fish from Owan
River, Edo State, Nigeria.
AB - The distribution of pesticides in water, sediments, Clarias gariepinus, and
Tilapia zilli from the Owan River was investigated to evaluate the pollution
status and potential hazard in the river system. A total of 16 pesticides were
analyzed using gas chromatography (GC) equipped with electron capture detector
(ECD). The concentration of pesticide residues ranged from ND to 0.43 MUg/l for
water samples, 0.82 to 2.14 MUg/kg/dw for sediment, 0.04 to 2.34 MUg/kg/ww for C.
gariepinus, and 0.02 to 1.73 MUg/kg/ww for T. zilli. High concentrations of
organochlorine pesticides, specifically benzenehexachloride (alpha-BHC, gamma
BHC, and beta-BHC) observed in all environmental media, are an indication of the
current illegal use of banned pesticides for agricultural activities in the
region. Analysis of data showed a strong correlation (r (2) = 0.7) between total
organic carbon (TOC) and total pesticide residues in sediment samples. Meanwhile,
risk quotient estimates for heptachlor epoxide, dieldrin, endrin,
dichlorodiphenyltrichloroethane (4,4'-DDT), endosulfan I, endosulfan II,
endosulfan aldehyde, and phosphomethylglycine showed potential risk to aquatic
organism under observed mean concentrations (risk quotient (RQ) >= 1). Estimated
average daily intake (EADI) for organochlorine pesticides (gamma-BHC, heptachlor
epoxide, aldrin, dieldrin, and endrin) was above their respective acceptable
average daily intake (ADI), while hazard quotient for each of these pesticides
was above the unity value (1). This indicates that there is a potential cancer
risk for the local residents with life time consumption of pesticide-contaminated
fish.
PMID- 26423633
TI - The concentrations of five heavy metals in components of an economically
important urban coastal wetland in Ghana: public health and phytoremediation
implications.
AB - Sakumo II is an urban wetland and a receptacle for domestic and industrial wastes
from two cities in Ghana. It however supports viable populations of fish and
crabs, is cultivated for food crops and grazed by farm animals. Components of the
wetland can therefore accumulate pollutants, but the public health and
phytoremediation implications of this are yet to be evaluated. We analysed Cd,
As, Hg, Cu and Pb in the lagoon water, sediment, green algae, eight species of
aquatic macrophytes, seven species of arthropods and one species of fish. The
concentrations of Pb were generally below detection limit whilst Cu was detected
only in the lagoon water and Pheropsophus vertialis. Cadmium ranged from 21 +/- 4
ppb in algae to 69 +/- 12 ppb in Typha domingensis and was generally higher than
As and Hg. The highest concentration of As was 11.7 +/- 2.1 ppb in Pistia
stratiotes whilst Hg was highest in lagoon water (4 +/- 2 ppb). The Cd
concentrations generally, and Hg concentrations in macrophytes, were higher than
US EPA guidelines indicating the wetland's resources were unsafe for regular
consumption. Among the emergent aquatic macrophytes, T. domingensis, Ludwigia sp.
and Paspalum vaginatum, respectively, had the highest accumulation capacity for
Cd, As and Hg, but the floating aquatic plant P. stratiotes appeared to be a
better accumulator of Cd and As.
PMID- 26423634
TI - Sewage-fed aquaculture: a sustainable approach for wastewater treatment and
reuse.
AB - This study assesses the long-term sustainability for operation and maintenance
(O&M) of sewage-fed aquaculture-based sewage treatment system. The study focused
on the integrated assessment of an engineered pond system of 8 million liters per
day capacity in the city of Karnal, the State of Haryana, northern India. Major
areas during the assessment included health, environmental, societal and
institutional views aspects as well as the quality of treated effluent subjected
for reuse. The treatment facility met the Indian regulatory standards (downstream
reuse and discharge into the legally permitted water bodies) in terms of physical
chemical parameters. The total coliform and faecal coliform removal were up to 2
3 log units; nevertheless, it was not capable to come across the bacterial count
requirement (<1,000 per 100 mL to minimise human health risk in aquaculture
practices). The system was able to generate sufficient net income required for
routine O&M. Annual revenue collected by the Municipal Corporation from the lease
of the facility as well as selling of treated wastewater was $3,077 and $16,667
$25,000, respectively. The additional benefit from the facility for the farmers
included the saving of fertilizers and cheapest source of water available for
irrigation. Recycling of treated sewages for irrigation is also returned
nutrients to the surrounding farms in Karnal. This exercise has saved significant
quantities of chemical fertilizer (26-41 Ton of nitrogen, 10-18 Ton of
phosphorous and 38-58 Ton of potassium per year) and the overall benefit for
farmers during cultivation of one acre of crop was calculated to be approximately
$133 per year.
PMID- 26423635
TI - A reference-based approach for estimating leaf area and cover in the forest
herbaceous layer.
AB - Cover data are used to assess vegetative response to a variety of ecological
factors. Estimating cover in the herbaceous layer of forests presents a problem
because the communities are structurally complex and rich in species. The
currently employed techniques for estimating cover are less than optimal for
measuring such rich understories because they are inaccurate, slow, or
impracticable. A reference-based approach to estimating cover is presented that
compares the area of foliar surfaces to the area of an observer's hand. While
this technique has been used to estimate cover in prior studies, its accuracy has
not been tested. We tested this hand-area method at the individual plant,
population, and community scales in a deciduous forest herbaceous layer, and in a
separate farm experiment. The precision, accuracy, observer bias, and species
bias of the method were tested by comparing the hand-estimated leaf area index
values with actual leaf area index, measured using a leaf area meter. The hand
area method was very precise when regressed against actual leaf area index at the
plant, population, and community scales (R(2) of 0.97, 0.93, and 0.87). Among the
deciduous sites, the hand-area method overestimated leaf area index consistently
by 39.1% at all scales. There was no observer bias detected at any scale, but
plant overestimation bias was detected in one species at the population scale.
The hand-area method is a rapid and reliable technique for estimating leaf area
index or cover in the forest herbaceous layer and should be useful to field
ecologists interested in answering questions at the plant, population, or
community level.
PMID- 26423636
TI - Patient-reported Outcome Measures in Radiotherapy: Clinical Advances and Research
Opportunities in Measurement for Survivorship.
AB - Patient-reported outcome measures (PROMs) are a useful way of recording patient
perceptions of the impact of their cancer and the consequences of treatment.
Understanding the impact of radiotherapy longer term requires tools that are
sensitive to change but also meaningful for patients. PROMs are useful in
defining symptom severity but also the burden of illness for cancer patients.
Patient-reported outcomes are increasingly being seen as a way to improve
practice by enhancing communication, improving symptom management as well as
identifying patient care needs. This paper provides an overview of the use of
PROMs in radiotherapy and considerations for tool choice, analysis and the
logistics of routine data collection. Consistent assessment is essential to
detect patient problems as a result of radiotherapy, but also to address emerging
symptoms promptly.
PMID- 26423637
TI - Using Administrative Data to Examine Health Disparities and Outcomes in
Neurological Diseases of the Elderly.
AB - The fields of neurodegenerative disease and dementia research have grown
considerably in the last several decades. Due to tremendous efforts of basic and
clinical research scientists, we know a great deal about dementia risk factors
and have multiple treatment options. Clinician recognition of cognitive
impairment has increased considerably, national policies which support screening
for and documenting cognitive dysfunction now exist, and public awareness of
neurodegenerative disease has never been greater. These conditions promote (and
demand) the growth of translational epidemiology and health services research,
which focuses on examining outcomes in groups of individuals as a function of
health care experiences. This review discusses the use of administrative data to
answer health care outcomes and disparities questions in dementia. Of particular
interest are publically available datasets that contain varying amounts of
diagnostic, clinical, pharmacy, and patient information. Methodological
challenges that are frequently encountered and must be understood to minimize
biased inference are also discussed.
PMID- 26423638
TI - Ex vivo tracing of pancreatic neuroendocrine tumors with bio-conjugated
fluorescent quantum dots: a paradigm of nanoparticle-based diagnostics.
PMID- 26423639
TI - Appetitive traits as behavioural pathways in genetic susceptibility to obesity: a
population-based cross-sectional study.
AB - The mechanisms through which genes influence body weight are not well understood,
but appetite has been implicated as one mediating pathway. Here we use data from
two independent population-based Finnish cohorts (4632 adults aged 25-74 years
from the DILGOM study and 1231 twin individuals aged 21-26 years from the
FinnTwin12 study) to investigate whether two appetitive traits mediate the
associations between known obesity-related genetic variants and adiposity. The
results from structural equation modelling indicate that the effects of a
polygenic risk score (90 obesity-related loci) on measured body mass index and
waist circumference are partly mediated through higher levels of uncontrolled
eating (betaindirect = 0.030-0.032, P < 0.001 in DILGOM) and emotional eating
(betaindirect = 0.020-0.022, P < 0.001 in DILGOM and betaindirect = 0.013-0.015,
P = 0.043-0.044 in FinnTwin12). Our findings suggest that genetic predispositions
to obesity may partly exert their effects through appetitive traits reflecting
lack of control over eating or eating in response to negative emotions. Obesity
prevention and treatment studies should examine the impact of targeting these
eating behaviours, especially among individuals having a high genetic
predisposition to obesity.
PMID- 26423640
TI - RIFM fragrance ingredient safety assessment, linalyl isobutyrate, CAS registry
number 78-35-3.
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 toxicity, reproductive toxicity, local respiratory
toxicity, phototoxicity, skin sensitization potential, as well as, environmental
safety. Reproductive toxicity was based on the Threshold of Toxicological Concern
(TTC) of 0.03 mg/kg/day for a Cramer Class I material. The estimated systemic
exposure is determined to be below this value while assuming 80% absorption from
skin contact and 100% from inhalation. A systemic exposure below the TTC value is
acceptable.
PMID- 26423641
TI - PrEP: why are we waiting?
PMID- 26423642
TI - Is monotherapy maintenance the way forward?
PMID- 26423643
TI - BMS-663068, a safe and effective HIV-1 attachment inhibitor.
PMID- 26423644
TI - Enhancing efforts to address infections.
PMID- 26423645
TI - Methadone treatment in primary care.
PMID- 26423646
TI - Is it time to abandon single intervention cure trials?
PMID- 26423647
TI - Liver disease in patients with HIV in sub-Saharan Africa.
PMID- 26423648
TI - HIV viral load messages should go viral in India.
PMID- 26423650
TI - Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in
treatment-experienced individuals: 24 week results of AI438011, a phase 2b,
randomised controlled trial.
AB - BACKGROUND: BMS-663068 is an oral prodrug of BMS-626529, an attachment inhibitor
that binds to HIV-1 gp120, blocking viral attachment to host CD4 cells. AI438011
is an ongoing trial investigating the efficacy, safety, and dose-response of BMS
663068 in treatment-experienced, HIV-1-infected patients. Herein we present the
results of the primary analysis. METHODS: AI438011 is a phase 2b, randomised,
active-controlled trial, at 53 hospitals and outpatient clinics across ten
countries in North and South America, Europe, and Africa. Individuals with an HIV
1 RNA viral load of at least 1000 copies per mL and a BMS-626529 half-maximum
inhibitory concentration lower than 100 nmol/L were randomly assigned (1:1:1:1:1)
to receive either BMS-663068 at 400 mg twice daily, 800 mg twice daily, 600 mg
once daily, or 1200 mg once daily or ritonavir-boosted atazanavir (300 mg of
atazanavir and 100 mg of ritonavir once daily), each with 400 mg of raltegravir
twice daily and 300 mg of tenofovir disoproxil fumarate once daily as a backbone.
The sponsor, participants, and investigators were masked for BMS-663068 dose but
not for allocation. Primary endpoints were the proportion of patients with an HIV
1 RNA viral load less than 50 copies per mL (response rate) at week 24 and the
frequency of serious adverse events and adverse events leading to
discontinuation, up to the week 24 analysis. The primary analyses included all
patients who received at least one dose of study drug (modified intention-to
treat population). This study is registered at ClinicalTrials.gov, NCT01384734.
FINDINGS: Between July 26, 2011, and July 16, 2012, 581 participants were
assessed for eligibility. Of these, 254 patients were randomly assigned to
receive either BMS-663068 (n=52 for the 400 mg twice daily group, n=50 for the
800 mg twice daily group, n=51 for the 600 mg once daily group, and n=50 for the
1200 mg once daily group) or ritonavir-boosted atazanavir (n=51). 200 patients
received at least one dose of BMS-663068, and 51 patients received at least one
dose of ritonavir-boosted atazanavir. At week 24, 40 (80%) of 50 patients in the
BMS-663068 400 mg twice daily group, 34 (69%) of 49 patients in the 800 mg twice
daily group, 39 (76%) of 51 patients in the 600 mg once daily group, and 36 (72%)
of 50 patients in the 1200 mg once daily group had an HIV-1 RNA viral load less
than 50 copies per mL, compared with 38 (75%) of 51 patients in the ritonavir
boosted atazanavir group. Serious adverse events were noted in 13 (7%) of 200
patients in the BMS-663068 groups and five (10%) of the 51 patients in the
ritonavir-boosted atazanavir group. Four (2%) of the 200 patients in the BMS
663068 groups and two (4%) of the 51 patients in the ritonavir-boosted atazanavir
group discontinued because of adverse events. No serious adverse events or
adverse events leading to discontinuation were BMS-663068-related. Grade 2-4
adverse events related to study drug(s) occurred in 17 (9%) of 200 patients
across the BMS-663068 groups and 14 (27%) of 51 patients in the ritonavir-boosted
atazanavir group. For the BMS-663068 groups these events were mostly single
instances with no dose relation and for the ritonavir-boosted atazanavir group
these were mostly gastrointestinal or hepatobiliary disorders associated with
hyperbilirubinaemia. INTERPRETATION: In a comparison with ritonavir-boosted
atazanavir, efficacy and safety of BMS-663068 up to the week 24 analysis support
continued development of BMS-663068, which is being assessed in a phase 3 trial
in heavily treatment-experienced individuals. FUNDING: Bristol-Myers Squibb.
PMID- 26423651
TI - Causes of hospital admission among people living with HIV worldwide: a systematic
review and meta-analysis.
AB - BACKGROUND: Morbidity associated with HIV infection is poorly characterised, so
we aimed to investigate the contribution of different comorbidities to hospital
admission and in-hospital mortality in adults and children living with HIV
worldwide. METHODS: Using a broad search strategy combining terms for hospital
admission and HIV infection, we searched MEDLINE via PubMed, Embase, Web of
Science, LILACS, AIM, IMEMR and WPIMR from inception to Jan 31, 2015, to identify
studies reporting cause of hospital admission in people living with HIV. We
focused on data reported after 2007, the period in which access to antiretroviral
therapy started to become widespread. We estimated pooled proportions of hospital
admissions and deaths per disease category by use of random-effects models. We
stratified data by geographical region and age. FINDINGS: We obtained data from
106 cohorts, with reported causes of hospital admission for 313 006 adults and
6182 children living with HIV. For adults, AIDS-related illnesses (25 119
patients, 46%, 95% CI 40-53) and bacterial infections (14 034 patients, 31%, 20
42) were the leading causes of hospital admission. These two categories were the
most common causes of hospital admission for adults in all geographical regions
and the most common causes of mortality. Common region-specific causes of
hospital admission included malnutrition and wasting, parasitic infections, and
haematological disorders in the Africa region; respiratory disease, psychiatric
disorders, renal disorders, cardiovascular disorders, and liver disease in
Europe; haematological disorders in North America; and respiratory, neurological,
digestive and liver-related conditions, viral infections, and drug toxicity in
South and Central America. For children, AIDS-related illnesses (783 patients,
27%, 95% CI 19-34) and bacterial infections (1190 patients, 41%, 26-56) were the
leading causes of hospital admission, followed by malnutrition and wasting,
haematological disorders, and, in the African region, malaria. Mortality in
individuals admitted to hospital was 20% (95% CI 18-23, 12 902 deaths) for adults
and 14% (10-19, 643 deaths) for children. INTERPRETATION: This review shows the
importance of prompt HIV diagnosis and treatment, and the need to reinforce
existing recommendations to provide chemoprophylaxis and vaccination against
major preventable infectious diseases to people living with HIV to reduce serious
AIDS and non-AIDS morbidity. FUNDING: None.
PMID- 26423649
TI - Protease inhibitor monotherapy for long-term management of HIV infection: a
randomised, controlled, open-label, non-inferiority trial.
AB - BACKGROUND: Standard-of-care antiretroviral therapy (ART) uses a combination of
drugs deemed essential to minimise treatment failure and drug resistance.
Protease inhibitors are potent, with a high genetic barrier to resistance, and
have potential use as monotherapy after viral load suppression is achieved with
combination treatment. We aimed to assess clinical risks and benefits of protease
inhibitor monotherapy in long-term clinical use: in particular, the effect on
drug resistance and future treatment options. METHODS: In this pragmatic,
parallel-group, randomised, controlled, open-label, non-inferiority trial, we
enrolled adults (>=18 years of age) positive for HIV attending 43 public sector
treatment centres in the UK who had suppressed viral load (<50 copies per mL) for
at least 24 weeks on combination ART with no change in the previous 12 weeks and
a CD4 count of more than 100 cells per MUL. Participants were randomly allocated
(1:1) to maintain ongoing triple therapy (OT) or to switch to a strategy of
physician-selected ritonavir-boosted protease inhibitor monotherapy (PI-mono); we
recommended ritonavir (100 mg)-boosted darunavir (800 mg) once daily or ritonavir
(100 mg)-boosted lopinavir (400 mg) twice daily, with prompt return to
combination treatment if viral load rebounded. All treatments were oral.
Randomisation was with permuted blocks of varying size and stratified by centre
and baseline ART; we used a computer-generated, sequentially numbered
randomisation list. The primary outcome was loss of future drug options, defined
as new intermediate-level or high-level resistance to one or more drugs to which
the patient's virus was deemed sensitive at trial entry (assessed at 3 years; non
inferiority margin of 10%). We estimated probability of rebound and resistance
with Kaplan-Meier analysis. Analyses were by intention to treat. This trial is
registered with the International Standard Randomised Controlled Trial Number
registry, number ISRCTN04857074. FINDINGS: Between Nov 4, 2008, and July 28,
2010, we randomly allocated 587 participants to OT (291) or PI-mono (296). At 3
years, one or more future drug options had been lost in two participants (Kaplan
Meier estimate 0.7%) in the OT group and six (2.1%) in the PI-mono group:
difference 1.4% (-0.4 to 3.4); non-inferiority shown. 49 (16.8%) participants in
the OT group and 65 (22.0%) in the PI-mono group had grade 3 or 4 clinical
adverse events (difference 5.1% [95% CI -1.3 to 11.5]; p=0.12); 45 (six treatment
related) and 56 (three treatment related) had serious adverse events.
INTERPRETATION: Protease inhibitor monotherapy, with regular viral load
monitoring and prompt reintroduction of combination treatment for rebound,
preserved future treatment options and did not change overall clinical outcomes
or frequency of toxic effects. Protease inhibitor monotherapy is an acceptable
alternative for long-term clinical management of HIV infection. FUNDING: National
Institute for Health Research.
PMID- 26423653
TI - Diethyl phthalate exposure is associated with embryonic toxicity, fatty liver
changes, and hypolipidemia via impairment of lipoprotein functions.
AB - Diethyl phthalates (DEPs) are notorious for their high potential toxicity in
endocrinological and reproduction systems in humans and animals. In this study,
we investigated the toxic effects of DEP on human lipoproteins, macrophages, and
zebrafish embryos. Treatment of human high-density lipoprotein (HDL) with DEP
caused oxidation, aggregation, and degradation of lipoproteins. DEP treatment
promoted foam cell formation via accelerated phagocytosis of LDL by macrophages
as well as exacerbated cellular senescence in human dermal fibroblasts. Injection
of DEP (final 5 MUM and 10 MUM) into zebrafish embryos caused severe embryo death
and slower developmental speed. Exposure of zebrafish embryos to water containing
DEP (final 11 and 22 ppm) caused early embryonic death along with the increased
oxidized products and impairment of skeletal development. Adult zebrafish exposed
to water containing DEP (final 11 and 22 ppm) for 4 weeks showed severe loss of
body weight under both normal diet (ND) and high cholesterol diet (HCD)
conditions. ND and HCD groups showed 59% and 49% reduction of plasma total
cholesterol (TC), respectively. Serum levels of hepatic inflammation enzymes
along with fatty liver changes were significantly elevated by DEP exposure. In
conclusion, DEP showed strong pro-atherogenic and pro-senescence effects via
severe lipoprotein modification in human cells. DEP caused impairment of
embryonic development and severe loss of body weight, hypolipidemia, and fatty
liver changes in zebrafish.
PMID- 26423652
TI - Effect of low-threshold methadone maintenance therapy for people who inject drugs
on HIV incidence in Vancouver, BC, Canada: an observational cohort study.
AB - BACKGROUND: HIV infection in people who inject drugs (PWID) is an international
public health concern. We aimed to assess the effect of methadone maintenance
therapy on HIV incidence in PWID in Vancouver, BC, Canada, where methadone is
widely available through family physicians' offices and dispensed by community
pharmacies. METHODS: Data were derived from the Vancouver Injection Drug Users
Study (VIDUS), a prospective cohort of PWID in Vancouver. Individuals were
eligible to enrol in VIDUS if they had injected illicit drugs at least once in
the previous month and lived in the Greater Vancouver region. Participants
responded to an interviewer-administered questionnaire and provided blood samples
at enrolment and follow-up visits every 6 months. We estimated time to HIV
seroconversion with Kaplan-Meier methods and used Cox proportional hazards
methods to assess associations between methadone use and time to seroconversion.
FINDINGS: 1639 HIV-negative individuals were recruited between May 1, 1996, and
May 31, 2013. Of these individuals, 138 had HIV seroconversion during a median of
75.5 months (IQR 33.4-115.3) of follow-up. In multivariate Cox regression
analyses, methadone maintenance therapy remained independently associated with a
reduced hazard of HIV infection after adjustment for sociodemographic
characteristics and drug use patterns (adjusted relative hazard 0.64, 95% CI 0.41
0.98). INTERPRETATION: Methadone maintenance therapy for PWID made available
through primary care physicians and community pharmacies can help to achieve
public health goals such as reducing the spread of HIV. FUNDING: US National
Institutes of Health, Canada Research Chair, Canadian Institutes of Health
Research.
PMID- 26423654
TI - Dietary intake in adults with type 1 and type 2 diabetes: validation of the
Dietary Questionnaire for Epidemiological Studies version 2 FFQ against a 3-d
weighed food record and 24-h urinalysis.
AB - The Dietary Questionnaire for Epidemiological Studies version 2 (DQES v2) FFQ has
not been validated in adults with diabetes. The aim was to determine the
agreement between the DQES v2 FFQ and a 3-d weighed food record (WFR) and 24-h
urinalysis in adults with type 1 and type 2 diabetes. The DQES v2 FFQ and a 3-d
WFR were completed on one occasion for measurement of food and nutrient intake. A
24-h urine sample was provided for measurement of Na and K excretion.
Participants were sixty-seven adults with type 1 and type 2 diabetes recruited
from the community. Nutrient intake reported in the FFQ was within 20 % of the
corresponding intake level reported in the WFR for the majority of nutrients.
However, the 95 % limits of agreement showed large variation at an individual
level between the two methods. There was a weak to moderate correlation between
nutrient intake measured using the two methods and a moderate to high correlation
for food intake. Quintile analysis showed that for the majority of foods and
nutrients >60 % of participants were ranked within 1 quintile of the WFR ranking.
The weighted kappa values showed slight to moderate agreement between the two
methods. Na intake was under-estimated in the FFQ by 25 % and K intake was over
estimated by 5 % compared with the 24-h urinalysis. In adults with type 1 and
type 2 diabetes, it is appropriate to use the DQES v2 FFQ to measure food and
nutrient intake at a group level.
PMID- 26423655
TI - Visible light and near-infrared-responsive chromophores for drug delivery-on
demand applications.
AB - The need for temporal-spatial control over the release of biologically active
molecules has motivated efforts to engineer novel drug delivery-on-demand
strategies actuated via light irradiation. Many systems, however, have been
limited to in vitro proof-of-concept due to biocompatibility issues with the
photo-responsive moieties or the light wavelength, intensity, and duration. To
overcome these limitations, this paper describes a light actuated drug delivery
on-demand strategy that uses visible and near-infrared (NIR) light and
biocompatible chromophores: cardiogreen, methylene blue, and riboflavin. All
three chromophores are capable of significant photothermal reaction upon exposure
to NIR and visible light, and the amount of temperature change is dependent upon
light intensity, wavelength as well as chromophore concentration. Pulsatile
release of bovine serum albumin (BSA) from thermally responsive hydrogels was
achieved over 4 days. These findings have the potential to translate light
actuated drug delivery-on-demand systems from the bench to clinical applications
that require explicit control over the presentation of biologically active
molecules.
PMID- 26423657
TI - Optimization of the score cutoff value for routine identification of
Staphylococcus species by matrix-assisted laser desorption ionization-time-of
flight mass spectrometry.
AB - Staphylococcus species are important pathogens. We evaluated 2 score cutoffs (2.0
and 1.7) and the replicate number (a single or a duplicate test) on the
identification of staphylococci using the Bruker matrix-assisted laser desorption
ionization-time-of-flight mass spectrometry (MALDI-TOF MS). A collection of 440
clinical isolates (11 species) and 144 reference strains (36 species) was
evaluated. For clinical isolates using a cutoff of 2.0 and duplicate tests, the
rates of species, genus, and unreliable identifications were 93.4%, 5.7%, and
0.9% respectively, while the respective values were 99.3%, 0.2%, and 0.5% when
the cutoff was 1.7. The species identification rates were significantly higher
(P<0.01) when a cutoff of 1.7 or a duplicate test was used. Similar results were
obtained for reference strains. In conclusion, a cutoff of 1.7 and duplicate
tests are recommended for identification of staphylococci using MALDI-TOF MS.
PMID- 26423656
TI - Copy number variation in the region harboring SOX9 gene in dogs with
testicular/ovotesticular disorder of sex development (78,XX; SRY-negative).
AB - Although the disorder of sex development in dogs with female karyotype (XX DSD)
is quite common, its molecular basis is still unclear. Among mutations underlying
XX DSD in mammals are duplication of a long sequence upstream of the SOX9 gene
(RevSex) and duplication of the SOX9 gene (also observed in dogs). We performed a
comparative analysis of 16 XX DSD and 30 control female dogs, using FISH and MLPA
approaches. Our study was focused on a region harboring SOX9 and a region
orthologous to the human RevSex (CanRevSex), which was located by in silico
analysis downstream of SOX9. Two highly polymorphic copy number variable regions
(CNVRs): CNVR1 upstream of SOX9 and CNVR2 encompassing CanRevSex were identified.
Although none of the detected copy number variants were specific to either
affected or control animals, we observed that the average number of copies in
CNVR1 was higher in XX DSD. No copy variation of SOX9 was observed. Our extensive
studies have excluded duplication of SOX9 as the common cause of XX DSD in
analyzed samples. However, it remains possible that the causative mutation is
hidden in highly polymorphic CNVR1.
PMID- 26423658
TI - Comparison of three real-time PCR assays for the detection of Chlamydia
trachomatis and Neisseria gonorrhoeae in young pregnant women.
AB - We compared 3 commercial real-time PCR assays, the Abbott RealTime CT/NG, the
cobas(r) 4800 CT/NG, and the Cepheid Xpert(r) CT/NG, for the detection of
Chlamydia trachomatis and Neisseria gonorrhoeae in vaginal swabs collected
prospectively from pregnant women aged <25 years. The overall agreement among 2
assays ranged from 98.9% to 99.5% with a kappa score between 0.94 and 0.97 for C.
trachomatis. For N. gonorrhoeae, the overall agreement was 100%. All kits allowed
prompt and specific results for C. trachomatis and N. gonorrhoeae in young
pregnant women.
PMID- 26423659
TI - The required minimum length of video sequences for obtaining a reliable
interobserver diagnosis in wrist arthroscopies.
AB - PURPOSE: To examine the relationship between video length for wrist arthroscopy
and interobserver reliability. MATERIALS AND METHODS: 100 consecutive wrist
arthroscopies were documented by long and short videos of the radiocarpal and the
midcarpal joints. The long videos were about twice as long as the short videos.
They were presented randomly to two independent and blinded examiners. Their
diagnoses were compared to the diagnoses made by the surgeon who performed the
arthroscopies. Kappa coefficients were calculated. RESULTS: Kappa statistics were
inconsistent and did not show that the long video provided an obvious advantage
over the short video. The Kappa coefficients of the two examiners for the
assessment of the cartilage status were 0.524 and 0.700 for the long videos and
0.465 and 0.639 for the short videos, respectively. The examiners diagnosed twice
as many false-positive cartilage lesions on short videos than on long videos. The
assessment of ligament lesions was more accurate on long than on short videos.
CONCLUSIONS: The results confirmed the hypothesis that the reproducibility of
diagnoses based on video documents was influenced by the length of the video
sequences. Therefore, it may be advisable for video documentation to be done
diligently. The video sequence of the radiocarpal joint should last about 60 s,
and that of a midcarpal joint should last about 45 s. Videos of difficult joints
should last appropriately longer. LEVEL OF EVIDENCE: Diagnostic II.
PMID- 26423660
TI - The combined CO2 laser and photodynamic therapy of multiple BCC's in a facial
port wine stain.
PMID- 26423661
TI - Radioprotective 105kDa protein (RP105): Is a critical therapeutic target for
alleviating ischemia reperfusion induced myocardial damage via TLR4 signaling
pathway.
PMID- 26423662
TI - Ultrahigh and Broad Spectral Photodetectivity of an Organic-Inorganic Hybrid
Phototransistor for Flexible Electronics.
AB - The creation of new organic-inorganic phototransistors with high and broad
spectral photosensitivity is reported. The extended charge transport and
photoconductivity between the layers in the bilayer structure results in a
notable detectivity of over 10(12) Jones and a linear dynamic range of over 100
dB at a broad spectral bandwidth across the UV-NIR range. Furthermore, the
considerably reduced persistent photocurrent effect of In-Ga-Zn-O (IGZO)-based
hybrid phototransistors is first demonstrated via an organic-inorganic bilayer
approach.
PMID- 26423663
TI - Developmental coordination disorder: core sensori-motor deficits, neurobiology
and etiology.
AB - Among developmental disorders, DCD is one of the least studied and less
understood one (Bishop, 2010). This review summarizes the current understanding
of developmental coordination disorder in neuropsychology with a focus mainly on
high level sensorimotor impairments, its etiology and its neural bases. We
summarize these core deficits in the framework of an influent motor control model
(Blakemore et al., 2002). DCD has several environmental risk factors which
probably interplay with genetic factors but those have not been sufficiently
identified. High-level sensori-motor deficits are probably multifactorial in DCD
and involve predictive coding deficits as well as weaknesses in perceptual and
sensory integration. At the brain level, DCD is associated with impaired
structure and functions within the motor network. Throughout the review we
highlight exciting new findings as well as potential future lines of research to
provide a more comprehensive understanding of this disorder.
PMID- 26423664
TI - Brain response during the M170 time interval is sensitive to socially relevant
information.
AB - Deciphering the social meaning of facial displays is a highly complex
neurological process. The M170, an event related field component of MEG
recording, like its EEG counterpart N170, was repeatedly shown to be associated
with structural encoding of faces. However, the scope of information encoded
during the M170 time window is still being debated. We investigated the neuronal
origin of facial processing of integrated social rank cues (SRCs) and emotional
facial expressions (EFEs) during the M170 time interval. Participants viewed
integrated facial displays of emotion (happy, angry, neutral) and SRCs (indicated
by upward, downward, or straight head tilts). We found that the activity during
the M170 time window is sensitive to both EFEs and SRCs. Specifically, highly
prominent activation was observed in response to SRC connoting dominance as
compared to submissive or egalitarian head cues. Interestingly, the processing of
EFEs and SRCs appeared to rely on different circuitry. Our findings suggest that
vertical head tilts are processed not only for their sheer structural variance,
but as social information. Exploring the temporal unfolding and brain
localization of non-verbal cues processing may assist in understanding the
functioning of the social rank biobehavioral system.
PMID- 26423667
TI - FASD Prevalence among Schoolchildren in Poland.
AB - BACKGROUND: Prenatal Alcohol Exposure is a major cause of brain damage and
developmental delay, known as Fetal Alcohol Spectrum Disorders (FASD) but in
Poland is rarely diagnosed and the scale of problem is not known. METHODS: An
active case ascertainment approach was applied to estimate the prevalence of FASD
among 7-9 years olds. Pre-screening was conducted in 113 randomly selected
regular and special schools. In the screening phase participated 280 children
(54% from the risk group, 60% boys). The entire number of eligible students (N =
2500) was taken as a denominator. RESULTS: The prevalence of FASD is not lower
than 2%, including 0.4% of Fetal Alcohol Syndrome. CONCLUSIONS:
Neurodevelopmental disorders associated with PAE are a serious challenge for the
public health system. Development of procedures and services to diagnose and to
support individuals affected by PAE and their families is an urgent need in
Poland.
PMID- 26423666
TI - Expression and Significance of COX-2 and Ki-67 in Hepatolithiasis with Bile Duct
Carcinoma.
AB - BACKGROUND: As an induced enzyme, COX-2 expression is elevated under stimuli from
inflammatory mediator or growth factor product. Ki-67, a cell cycle-related
proliferative antigen, reflects the tissue proliferative activity. This study
analyzed the expressional profile of cyclooxygenase-2 (COX-2) and Ki-67 in
hepatolithiasis and bile duct carcinoma tissues, in an attempt to provide
evidence for diagnosis and prognosis prediction of disease. MATERIAL AND METHODS:
A cohort of tissue samples from hepatolithiasis with bile duct carcinoma (N=47)
patients were analyzed using immunohistochemical (IHC) staining method for the
expression of COX-2 and Ki-67, in parallel with hepatolithiasis (N=44) and normal
bile duct tissues (N=30). The relationship between expression pattern of COX-2
and Ki-67 and pathological conditions was also analyzed, in addition to the
correlation with positive expression in hepatolithiasis samples. RESULTS: The
positive expression rate of COX-2 and Ki-67 in bile duct carcinoma was 76.6% and
80.9%, respectively, and was significantly higher than those in the
hepatolithiasis group, which was also higher than the control group. Expression
of both COX-2 and Ki-67 is closely related to TNM staging, lymph node metastasis,
and differentiation stage. They were also correlated with the mortality rate of
patients. CONCLUSIONS: Both COX-2 and Ki-67 are abundantly expressed in
hepatolithiasis and bile duct carcinoma tissues and may play an important role in
the disease occurrence, progression, and metastasis.
PMID- 26423665
TI - Genetic variation in the serotonin transporter gene influences ERP old/new
effects during recognition memory.
AB - Recognition memory is defined as the ability to recognize a previously
encountered stimulus and has been associated with spatially and temporally
distinct event-related potentials (ERPs). Allelic variations of the serotonin
transporter gene (SLC6A4) have recently been shown to impact memory performance.
Common variants of the serotonin transporter-linked polymorphic region (5HTTLPR)
of the SLC6A4 gene result in long (l) and short (s) allelic variants with
carriers of the s allele having lowered transcriptional efficiency. Thus, the
current study examines the effects polymorphisms of the SLC6A4 gene have on
performance and ERP amplitudes commonly associated with recognition memory.
Electroencephalogram (EEG), genetic, and behavioral data were collected from
sixty participants as they performed an item and source memory recognition task.
In both tasks, participants studied and encoded 200 words, which were then mixed
with 200 new words during retrieval. Participants were monitored with EEG during
the retrieval portion of each memory task. EEG electrodes were grouped into four
ROIs, left anterior superior, right anterior superior, left posterior superior,
and right posterior superior. ERP mean amplitudes during hits in the item and
source memory task were compared to correctly recognizing new items (correct
rejections). Results show that s-carriers have decreased mean hit amplitudes in
both the right anterior superior ROI 1000-1500ms post stimulus during the source
memory task and the left anterior superior ROI 300-500ms post stimulus during the
item memory task. These results suggest that individual differences due to
genetic variation of the serotonin transporter gene influences recognition
memory.
PMID- 26423668
TI - The Viable Violinist.
AB - In the aftermath of the Kermit Gosnell trial and Giubilini and Minerva's article
'After-birth abortion', abortion-rights advocates have been pressured to provide
an account of the moral difference between abortion, particularly late-term
abortion, and infanticide. In response, some scholars have defended a moral
distinction by appealing to an argument developed by Judith Jarvis Thomson in A
defense of abortion. However, once Thomson's analogy is refined to account for
the morally relevant features of late-term pregnancy, rather than distinguishing
between late-term abortion and infanticide, it reinforces their moral similarity.
This is because late-term abortion requires more than detachment - it requires an
act of feticide to ensure the death of the viable fetus. As such, a Thomsonian
account cannot be deployed successfully as a response to Giubilini and Minerva.
Those wishing to defend late-term abortion while rejecting the permissibility of
infanticide will need to provide an alternative account of the difference, or
else accept Giubilini and Minerva's conclusion.
PMID- 26423669
TI - Genetic diversity within ITS-1 region of Eimeria species infecting chickens of
north India.
AB - Coccidiosis, caused by apicomplexan parasites of the genus Eimeria, inflicts
severe economic losses to the poultry industry around the globe. In the present
study, ITS-1 based species specific nested PCR revealed prevalence of E.
acervulina, E. brunetti, E. maxima, E. mitis, E. praecox, E. necatrix and E.
tenella in 79.2%, 12.5%, 64.6%, 89.6%, 60.4%, 64.6% and 97.9% poultry farms of
north India, respectively. The ITS-1 sequences of different Eimeria spp. from
north India were generated and analyzed to establish their phylogenetic
relationship. The sequence identity with available sequences ranged from 80 to
100% in E. tenella, 95 to 100% in E. acervulina, 64 to 97% in E. necatrix, 96 to
99% in E. brunetti and 97 to 98% in E. mitis. Only long ITS-1 sequences of E.
maxima could be generated in the present study and it had 80-100% identity with
published sequences. Two out of the four ITS-1 sequences of E. maxima had
mismatches in the published nested primer sequences from Australia, while one
sequence of E. necatrix had a mismatch near 3' end of both forward and reverse
published nested primer sequences, warranting for the need of designing new set
of degenerate primers for these two species of Eimeria. In the phylogenetic tree,
all isolates of E. acervulina, E. brunetti, E. mitis, E. tenella and E. necatrix
clustered in separate clades with high bootstrap value. E. maxima sequences of
north Indian isolates grouped in a long form of E. maxima clade. Complete ITS-1
sequences of E. necatrix and E. mitis are reported for the first time from India.
Further studies are required with more number of isolates to verify whether these
differences are unique to geographical locations.
PMID- 26423670
TI - Genotyping and molecular analysis of Enterocytozoon bieneusi isolated from
immunocompromised patients in Iran.
AB - Microsporidia are known as opportunistic unicellular pathogens, particularly so
in individuals with congenital or acquired immunodeficiency. Enterocytozoon
bieneusi is one of the most common species infecting both immunocompromised and
immunocompetent individuals. The aim of this study was to assess the distribution
of E. bieneusi genotypes among immunocompromised patients in Iran. From 329 stool
samples referred for parasitological analysis during 2011-2014, 14 samples from
immunocompromised patients proving positive for E. bieneusi by SSU rDNA analysis
were selected. Genotyping was carried out using specific primers targeting the
Internal Transcribed Spacer (ITS) region. Subsequently, all samples were
sequenced and results queried against the GenBank database. Moreover, sequences
were subject to phylogenetic analysis. The expected amplification product was
generated for all samples. Genotype D was identified in patients with HIV+/AIDS,
transplant recipients, and cancer patients, while Genotype E was identified only
in cancer and HIV+/AIDS patients. Phylogenetic analysis revealed that there was
no relationship between genotypes and types of immunosuppression, whereas most
genotype D isolates grouped with those described previously from cattle, horses,
birds, and humans. E. bieneusi genotype D appears to be the most frequent
genotype in immunocompromised patients, while Genotype E was observed only in
HIV+/AIDS patients and cancer patients, not transplant recipients.
PMID- 26423671
TI - Approaches to characterize extended spectrum beta-lactamase/beta-lactamase
producing Escherichia coli in healthy organized vis-a-vis backyard farmed pigs in
India.
AB - The study was undertaken to investigate the occurrence and to characterize the
ESBL/beta-lactamase producing-Escherichia coli in healthy pigs of organized and
backyard farms in West Bengal, India. Total 200 rectal swabs were collected
randomly from healthy pigs maintained in four organized farms and 10 backyard
farms (n=100 each) and 76 isolates were identified as E. coli from organized
(48/100, 48%) and backyard pigs (28/100, 28%). Twelve E. coli isolates (6%) in
the present study were detected to possess any of the ESBL/beta-lactamase genes
studied. ESBL/beta-lactamase producers were isolated with significantly more
frequency from backyard pigs than the organized farm pigs (p=0.026). Six of
ESBL/beta-lactamase producing isolates were phenotypically confirmed as CTX-M
producers and ten of them were confirmed as TEM/SHV producers. PCR and sequencing
of the amplified product from representative isolates revealed the presence of
blaCTX-M-9, blaSHV-12 and blaTEM-1. No unique combination of the studied beta
lactamase genes for organized and backyard farm pig isolates was noted. The ESBL
isolates belonged to O13, O55, O133, O153, O157, O158, O166, rough and OUT
serogroups. The association of heat labile toxin (elt) (p<0.0005) with organized
farm isolates and heat stable toxin (estA) (p=0.0143) with backyard piggery
sector was significantly higher. The ESBL/beta-lactamase producers from organized
farm (Ak/Ex) and indigenous pigs (Ak/Ex/Te; Ak/CoT/G) showed a characteristic
phenotypical antibiotic resistance pattern. Two pairs of isolates from organized
and backyard farm pigs showed clonal relationship indicating a possible
transmission between the farms which were situated adjacently. Thus the present
study revealed backyard farm pigs as major source of ESBL/beta-lactamase
producing-E. coli associated with STa and characteristic antibiotic resistance
pattern in India.
PMID- 26423672
TI - Measurement of Foveal Avascular Zone Dimensions and its Reliability in Healthy
Eyes Using Optical Coherence Tomography Angiography.
AB - PURPOSE: To measure foveal avascular zone (FAZ) dimensions in healthy eyes using
optical coherence tomography angiography (OCTA) and calculate interobserver
variability. DESIGN: Reliability analysis. METHODS: Thirty-four eyes of 17
healthy subjects underwent OCTA at the Retina Service of Wills Eye Hospital. Two
masked graders performed measurements of FAZ dimensions including area,
perimeter, and maximum horizontal and vertical diameters using ImageJ. Intraclass
correlation coefficient (ICC) between graders was calculated. RESULTS: Mean area
(mm(2)), perimeter (mm), and maximum horizontal and vertical diameters (mm) were
0.27 +/- 0.101, 2.21 +/- 0.451, 0.59 +/- 0.126, and 0.56 +/- 0.118, respectively,
at the superficial and 0.34 +/- 0.116, 2.50 +/- 0.462, 0.69 +/- 0.123, and 0.63
+/- 0.110 at the deep network. Interobserver agreement was high for all
superficial FAZ measurements (ICC >=0.90) but did not meet the lowest acceptable
grader agreement for the deep vascular network (ICC <0.85). Fellow eyes had
statistically similar values (P > .05). CONCLUSION: Manual measurement of FAZ
dimensions using OCTA is a noninvasive and reliable method for quantifying FAZ at
the superficial vascular network. Assessing FAZ alterations in the deep vascular
network may be subject to greater interobserver variability.
PMID- 26423673
TI - Interpreters' subjective experiences of interpreting for refugees in person and
via telephone in health and behavioural health settings in the United States.
AB - Interpreters, whether in person or via telephonic means, are used in healthcare
settings to aid communication between clinicians and clients when the same
language is not shared. Refugees seeking health and behavioural healthcare often
have multiple needs and experiences of trauma that can complicate the provision
of services. Little is known about the interpreters' experiences in providing in
person and telephonic interpreting for refugees. This qualitative study sought to
understand the subjective experiences of interpreters in providing in-person and
telephone interpretations to refugees in healthcare settings in the United
States. Constant comparative analysis was used to analyse the transcribed, audio
taped individual, semi-structured interviews of 36 interpreters. These interviews
were conducted between July 2013 and July 2014. Two themes were identified: (i)
the importance for the interpreter to develop trust with the client; and (ii)
working with refugees requires more attention from the interpreter. The
interpreters of this study describe experiencing additional challenges in working
with refugees versus other clients. Recommendations based on the findings are
made.
PMID- 26423675
TI - Mesh Location in Open Ventral Hernia Repair: A Systematic Review and Network Meta
analysis.
AB - There is no consensus on the ideal location for mesh placement in open ventral
hernia repair (OVHR). We aim to identify the mesh location associated with the
lowest rate of recurrence following OVHR using a systematic review and meta
analysis. A search was performed for studies comparing at least two of four
locations for mesh placement during OVHR (onlay, inlay, sublay, and underlay).
Outcomes assessed were hernia recurrence and surgical site infection (SSI).
Pairwise meta-analysis was performed to compare all direct treatment of mesh
locations. A multiple treatment meta-analysis was performed to compare all mesh
locations in the Bayesian framework. Sensitivity analyses were planned for the
following: studies with a low risk of bias, incisional hernias, by hernia size,
and by mesh type (synthetic or biologic). Twenty-one studies were identified (n =
5,891). Sublay placement of mesh was associated with the lowest risk for
recurrence [OR 0.218 (95% CI 0.06-0.47)] and was the best of the four treatment
modalities assessed [Prob (best) = 94.2%]. Sublay was also associated with the
lowest risk for SSI [OR 0.449 (95% CI 0.12-1.16)] and was the best of the 4
treatment modalities assessed [Prob (best) = 77.3%]. When only assessing studies
at low risk of bias, of incisional hernias, and using synthetic mesh, the
probability that sublay had the lowest rate of recurrence and SSI was high.
Sublay mesh location has lower complication rates than other mesh locations.
While additional randomized controlled trials are needed to validate these
findings, this network meta-analysis suggests the probability of sublay being the
best location for mesh placement is high.
PMID- 26423674
TI - The Learning Curve of Robotic-Assisted Low Rectal Resection of a Novice Rectal
Surgeon.
AB - BACKGROUND: With the increasing availability of the surgical robotic system, the
young generation colorectal surgeons may learn robotic-assisted rectal surgery
upfront. There are currently very limited studies evaluating the learning curve
of novice rectal surgeons. OBJECTIVE: This study aimed to evaluate the learning
curve of a surgeon who had limited experience in open and laparoscopic rectal
surgery. METHODS: Thirty-nine consecutive robotic-assisted total mesorectal
excisions were performed from March 2013 to October 2014. All cases were
performed by a single surgeon whose prior experience in open or laparoscopic low
rectal cancer resections was <5 cases. The learning curve was analyzed using the
cumulative sum method. RESULTS: Thirty-four low anterior resections, four
abdomino-perineal resections, and one Hartmann's operation were performed. The
mean total operating time was 397.2 +/- 184.3 min. There was no conversion. The
major complication rate was 10.3 %. When total operating time was analyzed with
the CUSUM method, three phases could be identified. They are the initial eight
cases, middle 17 cases, and the final 14 cases. The first phase consisted of more
proximal tumors (86.3 +/- 20.7 vs. 58.0 +/- 34.9 mm from anal verge, p = 0.04)
and was associated with a shorter total operating time (243.5 +/- 38.0 vs. 540.9
+/- 133.4 min, p = 0.000) and less estimated blood loss (81.3 +/- 25.9 vs. 168.8
+/- 99.5 ml, p = 0.02) compared to the second phase. When the third phase is
compared with the first and second phase, it has shorter total operating time
(310.6 +/- 164.5 vs. 44 5.7 +/- 179.8 min, p = 0.03). Complications rate were
12.5, 17.6, and 0 % for phase one, two, and three respectively. CONCLUSIONS: In
this study, the learning curve for a novice rectal surgeon was 25 cases. This is
comparable to those who have already mastered the technique with laparoscopic or
open approach. Surgical robotic system may have a role in shortening the learning
curve for low rectal resection.
PMID- 26423677
TI - Behavioral and Social Sciences for Personalized Medicine: Teaching with Novel
Methods.
PMID- 26423676
TI - Memory deficits associated with khat (Catha edulis) use in rodents.
AB - Khat products and chewing practices are common in East Africa, Middle East for
centuries with concomitant socio-economic and public health repercussions. We
assessed memory deficits associated with khat use in rodents. Young male CBA
mice, 5-7 weeks old (n = 20), weighing 25-35 g were used. Mice were treated with
either 40, 120 or 360 mg/kg body weight (bw) methanolic khat extract, or 0.5 ml
saline for 10 days. Spatial acquisition, reversal and reference memory were
assessed using modified Morris Water maze (MMWM). Mice treated with 40 mg/kg khat
extract had longer (t4 = 4.12 p = 0.015) and t4 = 2.28 p = 0.065) escape latency
on first and second day during reversal relative to the baseline. Under 120 mg/kg
khat dose, the escape latency was shorter (t4 = -2.49 p = 0.05) vs (t3 = -2.5 p =
0.05) on third and fourth day. Further, treatment with 360 mg/kg khat extract
resulted in significantly longer time (49.13, 33.5, 40.2 and 35.75) vs. (23.5 s),
compared to baseline. Mice treated with khat or control preferred the target
quadrant post acquisition while differential pattern was seen during reversal
phase. Mice treated with 40 or 120 mg/kg khat showed significant preference for
target quadrant. Substantial time (19.9) was spent in the old target compared to
the new (16.9 s) by animals treated with highest dose however, the difference was
not significant. There is a biological plausibility that chronic khat use may
induce memory deficits and impair cognitive flexibility. The differential
patterns of memory deficits may reflect the differences in dose effect as well as
time dependent impairment.
PMID- 26423678
TI - A Novel Resident-as-Teacher Rotation for Second-Year Psychiatry Residents.
PMID- 26423679
TI - Considerations of Ethics While Allowing Flexibility for Trainees: The Model and
The Rationale for the Model of the Yale Global Mental Health Program.
PMID- 26423680
TI - Exploring the Intersection of Mental Health and Humanities: the Dalhousie
Psychiatry Student Writing Competition.
PMID- 26423681
TI - Effects of Fatty Acids on CYP2A5 and Nrf2 Expression in Mouse Primary
Hepatocytes.
AB - Abnormal fatty acid metabolism is observed throughout nonalcoholic fatty liver
disease (NAFLD) pathogenesis, and fatty acid storage is an important inducing
factor in insulin resistance, lipid oxidation, hepatic cell damage, and
inflammation. During NAFLD pathogenesis, changes in blood and liver contents of
different fatty acid types also vary. Cytochrome P450 2A5 (CYP2A5), an important
enzyme in mouse liver, metabolizes many drugs and activates multiple pro
carcinogens with widely varying structures. According to the changes in liver
fatty acid profiles observed in NAFLD animal models developed in our laboratory
and others, saturated (PA/palmitic, and SA/stearic acids) and unsaturated
(OA/oleic, LA/linoleic, ALA/alpha-linolenic and AA/arachidonic acids) fatty acids
were selected to induce mouse primary hepatocytes, at concentrations under 1 mM,
as detected by MTT assay. After 24 h treatment with various fatty acid
concentrations and types, CYP2A5 mRNA and protein amounts, and enzyme activity
were determined by real-time PCR, Western blot, and Coumarin 7-hydroxylation,
respectively. Meanwhile, Nrf2 mRNA and protein levels were evaluated by real-time
PCR and Western blot. The results indicated that saturated fatty acids are more
potent in inducing CYP2A5 than unsaturated ones, except arachidonic acid. In
addition, the changes in CYP2A5 expression were consistent with the alterations
observed in Nrf2 expression, indicating that Nrf2 might play a regulatory role in
CYP2A5 expression.
PMID- 26423682
TI - A computer aided measurement method for unstable pelvic fractures based on
standardized radiographs.
AB - BACKGROUND: To set up a method for measuring radiographic displacement of
unstable pelvic ring fractures based on standardized X-ray images and then test
its reliability and validity using a software-based measurement technique.
METHODS: Twenty-five patients that were diagnosed as AO/OTA type B or C pelvic
fractures with unilateral pelvis fractured and dislocated were eligible for
inclusion by a review of medical records in our clinical centre. Based on the
input pelvic preoperative CT data, the standardized X-ray images, including
inlet, outlet, and anterior-posterior (AP) radiographs, were simulated using
Armira software (Visage Imaging GmbH, Berlin, Germany). After representative
anatomic landmarks were marked on the standardized X-ray images, the 2
dimensional (2D) coordinates of these points could be revealed in Digimizer
software (Model: Mitutoyo Corp., Tokyo, Japan). Subsequently, we developed a
formula that indicated the translational and rotational displacement patterns of
the injured hemipelvis. Five separate observers calculated the displacement
outcomes using the established formula and determined the rotational patterns
using a 3D-CT model based on their overall impression. We performed 3D
reconstruction of all the fractured pelvises using Mimics (Materialise, Haasrode,
Belgium) and determined the translational and rotational displacement using 3
matic suite. The interobserver reliability of the new method was assessed by
comparing the continuous measure and categorical outcomes using intraclass
correlation coefficient (ICC) and kappa statistic, respectively. RESULT: The
interobserver reliability of the new method for translational and rotational
measurement was high, with both ICCs above 0.9. Rotational outcome assessed by
the new method was the same as that concluded by 3-matic software. The agreement
for rotational outcome among orthopaedic surgeons based on overall impression was
poor (kappa statistic, 0.250 to 0.426). Compared with the 3D reconstruction
outcome, the interobserver reliability of the formula method for translational
and rotational measures was perfect with both ICCs more than 0.9. CONCLUSIONS:
The new method for measuring displacement using a formula was reliable, and could
minimise the measurement errors and maximise the precision of pelvic fracture
description. Furthermore, this study was useful for standardising the operative
plan and establishing a theoretical basis for robot-assisted pelvic fracture
surgery based on 2-D radiographs.
PMID- 26423683
TI - Long term quality of life in patients with Hirschsprung's disease who underwent
heart-shaped anastomosis during childhood: A twenty-year follow-up in China.
AB - OBJECTIVE: The aim of this study was to evaluate the long term quality of life
among adults who had undergone heart-shaped anastomosis for Hirschsprung's
disease (HD) during childhood. METHODS: Ninety-two cases with HD who had
undergone heart-shaped anastomosis between January 1986 and January 1995 were
investigated, and 90 adults with pediatric surgical and gastrointestinal
disorders during the same period were randomly collected to serve as controls.
They were to complete bowel function score (BFS) and WHO Quality of Life-BREF
(QLB). RESULTS: In BFS, there was significant difference in soiling between the
HD group and the control group. Eight patients presented occasional soiling, with
six of them having undergone two or more operations. Comparing persons without
soiling in the HD group and controls, no significant difference was found in each
area of QLB, and there was significant difference in psychology and low quality
of life subjective feelings in the soiling group compared with the other HD
persons and controls, respectively. CONCLUSION: The long-term outcome of heart
shaped anastomosis for Hirschsprung's disease is satisfying. Recurrent operation
is a high risk for soiling occurrence. It should be emphasized to remove all the
lesion segment in the first operation.
PMID- 26423684
TI - Surgical intervention strategies for pediatric congenital cystic lesions of the
lungs: A 20-year single-institution experience.
AB - BACKGROUND: The aim of this study was to assess surgical intervention strategies
for congenital cystic lesions of the lungs (CCL), focusing on the safety of lung
resection. MATERIALS AND METHODS: The clinical features of 27 children (CCAM,
n=16; bronchial atresia, n=4; bronchogenic cyst, n=3; pulmonary sequestration,
n=3; lobar emphysema, n=1) who were treated at our institution between 1995 and
2014 were analyzed. RESULTS: Of the 27 patients, 14 were asymptomatic, and 13
were symptomatic. The youngest symptomatic patient presented with pneumonia at
9months of age. The mean age at surgery was 4months in the asymptomatic group and
4.1years in the symptomatic group. The mean operating time was 167minutes in the
asymptomatic group and 275minutes in the symptomatic group (P<0.001). The mean
amount of intraoperative bleeding was 15g in the asymptomatic group and 83.4g in
the symptomatic group (P<0.05). All of the prenatally diagnosed patients
underwent surgery within six months of birth. Three patients had remnant cystic
lesions, all of which involved cystic lesions located over the lobulation
anomalies of the lung. CONCLUSIONS: To minimize surgical invasiveness, surgery
for CCL should be performed during the asymptomatic period or within six months
after birth.
PMID- 26423685
TI - Acceleration of Proteinuria without Significant Impact on Renal Function and Its
Protection by Angiotensin II Receptor Blocker in Rats Treated with Axitinib.
AB - BACKGROUND: Proteinuria is a dose-associated adverse event induced by anti
angiogenic agents; however, the mechanism mediating the induction of proteinuria
by this type of agent remains largely unknown. The objective of this study was to
assess the effects of treatment with axitinib and/or angiotensin II receptor
blocker (ARB) on urinary protein excretion and renal function. MATERIALS AND
METHODS: Thirty-five rats were randomly selected for treatment with following
agents for 4 weeks: vehicle (group A), candesartan (group B), axitinib (group C),
axitinib plus candesartan (group D), or axitinib and no treatment for subsequent
2 weeks (group E). RESULTS: After completion of treatment schedule, urine protein
to-creatinine ratio (UPC) in group C was significantly higher than those in
groups A and B, while the additional administration of candesartan resulted in
the significant reduction of UPC in group D compared with group C. Following the
no treatment interval for 2 weeks, UPC in group E significantly decreased
compared with that in group C. There were no significant differences in serum
creatinine or blood urea nitrogen level among the five groups. Furthermore,
semiquantitative evaluation of immunofluorescence findings showed that the
expression levels of both nephrin and podocin in rat kidneys were inversely
associated with the UPC value throughout these five groups. CONCLUSIONS: Despite
the acceleration of proteinuria involving the downregulation of slit diaphragm
associated proteins, axitinib may not have an adverse impact on renal function,
and axitinib-induced proteinuria can be partially prevented by additional
treatment with ARB and reversibly recovered by its transient dose-interruption.
PMID- 26423686
TI - Influence of endurance exercise training on antioxidant enzymes, tight junction
proteins, and inflammatory markers in the rat ileum.
AB - BACKGROUND: This study investigated the effects of endurance exercise training on
ileum antioxidant status, as well as tight junction, inflammatory, and nutrient
transporter gene expression. METHODS: Sprague-Dawley rats (4 month old) were
assigned to sedentary (SED) or endurance exercise-training (EXE) groups (n =
8/group). EXE animals were trained on the treadmill for 10 days at a speed of 30
m/min at 0 degrees incline for 60 min/day. SED and EXE animals were sacrificed
(24 h after the final training bout) and the ileum was stored for analyses.
RESULTS: The ileum of EXE had higher (p < 0.05) antioxidant protein levels of
manganese superoxide dismutase and catalase compared to SED with no change (p >
0.05) in the lipid peroxidation biomarker 4-hydroxynonenal. Ileum mRNA expression
of the tight junction gene zonulin increased (p < 0.05) and claudin 1 decreased
(p < 0.05) in EXE compared to SED, but occludin and zonula occluden 1 were not
different (p > 0.05) between SED and EXE. The ileum mRNA expressions of seven
nutrient transporters (SLC5A8, SLC7A6, SLC6A19, SLC7A7, SLC27A2, SLC16A10, and
SLC15A1) were not different between the two groups (p > 0.05). EXE had lower
ileum TNFalpha mRNA expression (p < 0.05) compared to SED. No changes (p > 0.05)
were found in the other inflammatory mRNAs including NFkappaB, IFNgamma, IL6,
CCL2, TLR4, and IL10. In addition, no changes in p-p65:p65 were detected.
CONCLUSIONS: These findings suggest that 10 days of endurance exercise training
up-regulates key endogenous antioxidant enzymes, decreases select inflammation
markers, and alters select markers of tight junction permeability.
PMID- 26423688
TI - Synergy of ambroxol with vancomycin in elimination of catheter-related
Staphylococcus epidermidis biofilm in vitro and in vivo.
AB - Central venous catheters are widely used in neonatal intensive care units (NICUs)
nowadays. The commonest cause of catheter-related bloodstream infections (CRBSIs)
is coagulase-negative staphylococci (CoNS). Ambroxol, an active metabolite of
bromhexine, exhibits antimicrobial activity against strains producing biofilm and
enhances the bactericidal effect of some antibiotic by breaking the structure of
biofilm. In this study, we aimed to determine the effect of ambroxol with
vancomycin on the biofilm of Staphylococcus epidermidis (S. epidermidis) in vitro
and in vivo. In the in vitro study, the biofilm of S. epidermidis was assessed by
XTT reduction assay and analysed by confocal laser scanning microscopy (CLSM). In
the in vivo study, a rabbit model of CRBSIs was created by intravenous intubation
with a tube covered with S. epidermidis biofilm. The rabbits received one of the
following four treatments by means of antibiotic lock therapy: normal heparin,
ambroxol, vancomycin, or vancomycin plus ambroxol each for 3 days. The
microstructure of the biofilm was assessed by scanning electron microscopy (SEM).
The number of bacterial colonies in the organs (liver, heart, and kidney) and on
the intravenous tubes was measured on agar plates. Pathological changes in the
organs (liver, heart, and kidney) were observed with Hematoxylin-Eosin staining.
The ambroxol exhibits significant efficacy to potentiate the bactericidal effect
of vancomycin on S. epidermidis biofilm both in vitro and in vivo. The antibiotic
lock therapy using a combination of ambroxol and vancomycin reveals a high
ability to eradicate S. epidermidis biofilms in vivo. These results provide the
basis of a useful anti-infection strategy for the treatment of CRBSIs.
PMID- 26423687
TI - Appropriateness of Prostate Cancer Imaging among Veterans in a Delivery System
without Incentives for Overutilization.
AB - OBJECTIVE: To determine the frequency of appropriate and inappropriate prostate
cancer imaging in an integrated health care system. DATA SOURCES/STUDY SETTING:
Veterans Health Administration Central Cancer Registry linked to VA electronic
medical records and Medicare claims (2004-2008). STUDY DESIGN: We performed a
retrospective cohort study of VA patients diagnosed with prostate cancer (N =
45,084). Imaging (CT, MRI, bone scan, PET) use was assessed among patients with
low-risk disease, for whom guidelines recommend against advanced imaging, and
among high-risk patients for whom guidelines recommend it. PRINCIPAL FINDINGS: We
found high rates of inappropriate imaging among men with low-risk prostate cancer
(41 percent) and suboptimal rates of appropriate imaging among men with high-risk
disease (70 percent). Veterans utilizing Medicare-reimbursed care had higher
rates of inappropriate imaging [OR: 1.09 (1.03-1.16)] but not higher rates of
appropriate imaging. Veterans treated in middle [OR: 0.51 (0.47-0.56)] and higher
[OR: 0.50 (0.46-0.55)] volume medical centers were less likely to undergo
inappropriate imaging without compromising appropriate imaging. CONCLUSIONS: Our
results highlight the overutilization of imaging, even in an integrated health
care system without financial incentives encouraging provision of health care
services. Paradoxically, imaging remains underutilized among high-risk patients
who could potentially benefit from it most.
PMID- 26423689
TI - Fulminant adenovirus hepatitis after hematopoietic stem cell transplant:
Retrospective real-time PCR analysis for adenovirus DNA in two cases.
AB - BACKGROUND: Viral infection is one of the major causes of mortality in patients
undergoing hematopoietic stem cell transplant (HSCT). Systemic infection of
adenovirus (AdV) has emerged as a not uncommon viral infection with significant
morbidity and mortality as with cytomegalovirus and Epstein-Barr virus infection.
Routine surveillance for these viruses has become a clinical practice and
subsequent preemptive therapy improves patients' outcomes; however, the
effectiveness of preemptive therapy for AdV has not been fully investigated in
patients with a lethal form of AdV infection. METHODS: Sequential AdV loads were
retrospectively analyzed in children with fulminant AdV hepatitis after HSCT.
RESULTS: The AdV DNA became detectable (1 * 10(4) copies/mL) as early as 2 weeks
after HSCT. These levels reached >1 * 10(8) copies/mL at the onset of fulminant
hepatitis. However, we determined that gamma-glutamyltransferase levels were
elevated to >100 IU/L at least 2 weeks before the diagnosis of hepatitis.
CONCLUSIONS: Our observation raises the possibility that elevated gamma
glutamyltransferase could be a sentinel marker for AdV hepatitis, which prompts
elaborated monitoring of AdV load and targeted treatment.
PMID- 26423690
TI - Fatal acute cardiac vasculopathy during cisplatin-gemcitabine-bevacizumab (CGB)
chemotherapy for advanced urothelial carcinoma.
AB - BACKGROUND: Bladder cancer (BC) accounts for ~14,680 deaths annually in the U.S.
The prognosis of advanced disease remains dismal with current therapies. A phase
III intergroup trial for metastatic BC adding bevacizumab to first-line cisplatin
gemcitabine chemotherapy (GCB regimen) is currently ongoing. We report the
clinical-pathologic findings of a patient who developed fatal acute cardiac
microvascular toxicity while receiving this regimen. CASE REPORT: A 66 year old
man consulted for epigastric pain, nausea, intermittent diarrhea and
lightheadedness two weeks after receiving the first cycle of GCB chemotherapy for
metastatic BC. Physical evaluation, laboratory studies and electrocardiogram
(EKG) were within normal limits except for marked thrombocytopenia that was
attributed to his recent chemotherapy. The patient was admitted for observation,
rehydrated and started on a proton pump inhibitor. The following day, however, he
experienced sudden severe chest and right upper quadrant pain. EKG showed
tachycardia, ST elevations in leads V2 and V3, laboratory analyses revealed
marked elevation of cardiac troponin I, and an echocardiogram showed a markedly
reduced ejection fraction of 10-20%, consistent with rapidly progressive
cardiogenic shock. Emergent cardiac catheterization showed no significant
coronary artery disease. Sepsis work-up was negative. He became progressively
hypotensive, developed multi-organ failure, and died 48 h after admission.
Postmortem examination showed diffuse microvasculopathy and changes due to global
hypoperfusion of 12-48 h evolution. CONCLUSIONS: We present the first case of
acute, fatal cardiac failure due to microvasculopathy most consistent with
bevacizumab-associated toxicity. The findings are discussed in light of the
existing literature.
PMID- 26423691
TI - Low Vitamin D Levels and Genetic Polymorphism in the Vitamin D Receptor are
Associated with Increased Risk of Statin-Induced Myopathy.
AB - The main aim of this study was to test the hypothesis whether 25-hydroxyvitamin D
(25OHD) levels <50 nmol/L at baseline could predict statin-induced myopathy
during the course of treatment. In addition, we analysed the association between
a genetic polymorphism in the vitamin D receptor (VDR) and the risk of statin
induced myopathy. We used serum samples from a prospective, observational study
in statin-treated patients in Sweden who were thoroughly followed with interviews
and questionnaires regarding muscular symptoms (n = 127). In this cohort, 16
developed muscular symptoms and 111 had no muscular symptoms associated with
statin treatment during the first year of follow-up. Patients with 25OHD levels
<50 nmol/L before starting on statin treatment had four times higher risk of
developing muscular symptoms compared with individuals having 25OHD levels >50
nmol/L (RR 4.2; 95% CI 1.7-10.2; p < 0.01). The mean levels of 25OHD at baseline
were 50 +/- 4 nmol/L among patients developing myopathy and 60 +/- 2 nmol/L among
patients without myopathy (p < 0.01). Individuals homozygous for the C allele in
the VDR polymorphism TaqI (rs731236) had a four times higher risk of developing
muscular symptoms; (RR 4.37, 95% CI 1.9-10.1, p < 0.01). In conclusion, 25OHD
levels <50 nmol/L might be a useful marker to predict muscular adverse events
during statin treatment. In addition, the finding that the VDR polymorphism TaqI
was associated with myopathy may indicate a causal relationship between vitamin D
function and myopathy, but larger studies are needed before firm conclusions can
be drawn.
PMID- 26423692
TI - Microscopic Investigation of Protein Function in C. elegans Using Fluorescent
Imaging.
AB - Caenorhabditis elegans is a powerful model organism for studying human biology
and disease due to its surprisingly high genetic homology to Homo sapiens. Its
genetic amenability, small size, short generation time, and transparent body make
it an ideal organism for multiple scientific disciplines. Fluorescent microscopy
is essential for studying protein biological function. However, C. elegans,
mainly due to its high motility, has been more difficult to adapt to fluorescence
imaging, especially live-imaging. We present here several protocols for the study
of protein location, function and dynamics in context of a whole animal. These
protocols, especially when combined with existing genetic procedures, can yield a
great deal of insight in the physiological roles of proteins in C. elegans, which
can be directly translated into mammalian systems.
PMID- 26423693
TI - In Vivo Immuno-Spin Trapping: Imaging the Footprints of Oxidative Stress.
AB - A plethora of disease processes are associated with elevated reactive species
formation and allied reactions with biomolecules that alter cell signaling,
induce overt damage, and promote dysfunction of tissues. Unfortunately, effective
detection of reactive species in tissues is wrought with issues that
significantly limit capacity for validating species identity, establishing
accurate concentrations, and identifying anatomic sites of production. These
shortcomings reveal the pressing need for new approaches to more precisely assess
reactive species generation in vivo. Herein, we describe an in vivo immuno-spin
trapping method for indirectly assessing oxidant levels by detecting free
radicals resulting from reaction of oxidants with biomolecules to form stable,
immunologically detectable nitrone-biomolecular adducts. This process couples the
reactivity and sensitivity of an electron paramagnetic resonance spin trap with
the resolution of confocal imaging to visualize the extent of cell and tissue
oxidation and anatomic sites of production by detecting resultant free radical
formation.
PMID- 26423694
TI - Getting a Handle on RAS-targeted Therapies: Cysteine Directed Inhibitors.
AB - Directly inhibiting oncogenic RAS proteins has proven to be an arduous task, as
after more than thirty years of intensive investigation, no clinically relevant
therapies exist. Recently, two classes of selective small molecule inhibitors
that target a cysteine-containing RAS mutant have been developed, representing
the first directed approaches to specifically inhibit an oncogenic KRAS mutant.
In this mini-review, we first assess the development and targeting strategies
associated with novel cysteine-directed RAS inhibitors. Next, we describe the
variable oncogenic potency of the KRAS G12C mutant when compared to other KRAS
G12 mutants. Lastly, we evaluate how the redox properties of KRAS G12C may play a
role in differential signaling and tumorigenic potency of the oncogene, the
efficacy of small molecules targeting this specific RAS mutant and further
development of directed oncogenic RAS inhibitors.
PMID- 26423695
TI - Past, Present, and Future of Targeting Ras for Cancer Therapies.
AB - For decades, mutant Ras (mut-Ras) proteins have been identified as drivers of
multiple cancers including pancreatic, lung, and colon cancers. However,
targeting this oncogene has been challenging and no Ras inhibitors are on the
market to date. Lately several candidates targeting the downstream pathways of
Ras signaling, including PI3K and Raf, were approved for cancer treatment.
However, they do not present promising therapeutic effects on patients harboring
Ras mutations. Recently, a variety of compounds have been reported to impair the
activity of Ras, and these exciting discoveries reignite the hope for development
of novel drugs targeting mut-Ras. In this article, we will review the progress
made in this field and the current state-of-the-art technologies to develop Ras
inhibitors. Also we will discuss the future direction of targeting Ras.
PMID- 26423698
TI - Arene ruthenium(II) Complexes: The Promising Chemotherapeutic Agent in Inhibiting
the Proliferation, Migration and Invasion.
AB - Arene ruthenium(II) complexes have been widely investigated as one of the most
promising candidates in chemotherapy because of their low toxicity and high
inhibiting activity against the proliferation, invasion, migration, and
angiogenesis of various tumors in vitro and in vivo. This review highlights the
recent developments in different chemical types of arene Ru(II) complexes, as
well as their biological activity and underlying mechanisms. The sustained
efforts in this aspect of arene Ru(II) complexes would be essential in developing
novel anti-tumor agents in the near future.
PMID- 26423699
TI - Ruthenium Complexes: An Emerging Ground to the Development of
Metallopharmaceuticals for Cancer Therapy.
AB - GLOBOCAN 2012 estimates 14.1 million new cancer cases and 8.2 million cancer
related deaths worldwide. Cancer is rapidly becoming a major public health
concern in India as well, with the number of new cancer cases anticipated to
double within the next 20 years. The percentage of currently approved
metallodrugs is very low, in contrast to the majority of drugs available as
organic compounds. The search for alternative drugs to cisplatin, carboplatin and
other derivatives is highly needed due to their severe side effects including
nephrotoxicity and neurotoxicity. Ruthenium, among other transition metal
complexes appears to be a possible candidate for cancer therapy in the near
future. The most significant rationale is ruthenium's octahedral chemistry and
greater propensity to undergo redox reactions. The hypoxic environment of tumors
favors the reduction of inert ruthenium (III) to active ruthenium (II) which
opens new prospects for the development of novel prodrugs. Although studies
suggest that ruthenium complexes penetrate well within the tumor cells and bind
effectively to DNA, its binding to proteins is not very well explained. Ruthenium
complexes are presently receiving great attention in the fields of biological,
pharmaceutical and medicinal chemistry as anticancer agents. This review poses a
comprehensive overview of the studies on competent anticancer ruthenium complexes
and the role of these metal complexes in relation to their anticancer properties
as well as those under clinical trials.
PMID- 26423697
TI - Ras Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic
Target.
AB - The K-, N-, and HRas small GTPases are key regulators of cell physiology and are
frequently mutated in human cancers. Despite intensive research, previous efforts
to target hyperactive Ras based on known mechanisms of Ras signaling have been
met with little success. Several studies have provided compelling evidence for
the existence and biological relevance of Ras dimers, establishing a new
mechanism for regulating Ras activity in cells additionally to GTP-loading and
membrane localization. Existing data also start to reveal how Ras proteins
dimerize on the membrane. We propose a dimer model to describe Ras-mediated
effector activation, which contrasts existing models of Ras signaling as a
monomer or as a 5-8 membered multimer. We also discuss potential implications of
this model in both basic and translational Ras biology.
PMID- 26423696
TI - How to Target Activated Ras Proteins: Direct Inhibition vs. Induced
Mislocalization.
AB - Oncogenic Ras proteins are a driving force in a significant set of human cancers
and wildtype, unmutated Ras proteins likely contribute to the malignant phenotype
of many more. The overall challenge of targeting activated Ras proteins has great
promise to treat cancer, but this goal has yet to be achieved. Significant
efforts and resources have been committed to inhibiting Ras, but these energies
have so far made little impact in the clinic. Direct attempts to target activated
Ras proteins have faced many obstacles, including the fundamental nature of the
gain-of-function oncogenic activity being produced by a loss-of-function at the
biochemical level. Nevertheless, there has been very promising recent pre
clinical progress. The major strategy that has so far reached the clinic aimed to
inhibit activated Ras indirectly through blocking its post-translational
modification and inducing its mislocalization. While these efforts to indirectly
target Ras through inhibition of farnesyl transferase (FTase) were rationally
designed, this strategy suffered from insufficient attention to the distinctions
between the isoforms of Ras. This led to subsequent failures in large-scale
clinical trials targeting K-Ras driven lung, colon, and pancreatic cancers.
Despite these setbacks, efforts to indirectly target activated Ras through
inducing its mislocalization have persisted. It is plausible that FTase
inhibitors may still have some utility in the clinic, perhaps in combination with
statins or other agents. Alternative approaches for inducing mislocalization of
Ras through disruption of its palmitoylation cycle or interaction with chaperone
proteins are in early stages of development.
PMID- 26423700
TI - RAS/Effector Interactions from Structural and Biophysical Perspective.
AB - RAS is a molecular switch that regulates a large number of pathways through
interactions with many effector proteins. Most RAS/effector complexes are short
lived, demonstrating fast association and fast dissociation rate and Kds ranging
from 10(-8)-10(-5) M, compatible with the signaling function of these
interactions in the cell. RAS effectors share little sequence homology but all
contain an RAS binding domain that exhibits ubiquitin fold. All effectors bind to
the same epitope on RAS by forming an intermolecular beta sheet and creating a
number of favorable hydrogen bonds and salt bridges across the binding interface.
Several hot-spots on both RAS and effector molecules constitute a general
recognition mode. RAS/effector interactions occur only when RAS is found in the
active, GTP-bound state, and are disrupted upon GTP hydrolysis, most probably due
to increased flexibility of the RAS molecule. Recent NMR studies demonstrate how
in the presence of multiple binding partners, RAS prefers certain effectors to
others. The hierarchy of these interactions could be altered for RAS oncogenic
mutants, thus perturbing the network of the downstream signaling. Insights
obtained through biophysical and structural studies of effectors interacting with
RAS and its mutants establish the basic principles that could be used for
designing drugs in RAS-associated diseases.
PMID- 26423701
TI - Direct Inhibitors of Ras-Effector Protein Interactions.
AB - Activating Ras mutations are associated with ~30% of all human cancers, which
often respond poorly to standard therapies. The four Ras isoforms are therefore
highly attractive targets for anticancer drug discovery. However, Ras proteins
function through protein-protein interactions and their surfaces lack any major
pockets for small molecules to bind; as a result they have been declared
"undruggable" for the past 30 years. Several breakthroughs during the past few
years may finally remove Ras from the list of undruggable proteins. This mini
review discusses the current approaches to developing inhibitors especially
cyclic peptides that physically block the interaction between Ras and its
downstream effector proteins, which is potentially the most effective approach
for treating Ras mutant cancers.
PMID- 26423702
TI - Outcomes of Treatment in Slovene Follicular Lymphoma Patients.
AB - BACKGROUND: The outcome of follicular lymphoma (FL) patients has dramatically
improved over the last 2 decades by introduction of rituximab in combination
chemotherapy and into maintenance setting. We retrospectively analyzed the
treatment outcomes in Slovene FL patients in the era of rituximab and compared
them to the results reported by pivotal clinical studies. PATIENTS AND METHODS:
Two hundred seventy-eight patients with FL treated in Slovenia between 2000 and
2010 with a median follow-up of 5.7 years were included in our retrospective
analysis. One hundred ninety-three (69%) received systemic treatment (ST).
RESULTS: With a median follow-up of 5.7 years, the 5- and 10-year overall
survival (OS) rates for the whole series were 77% and 53%, respectively. The 5
year progression-free survival (PFS) for 193 FL patients treated with ST was 37%.
Patients treated with rituximab chemotherapy had a significantly better OS than
patients treated with chemotherapy alone, with a 5-year OS of 79% versus 53%
(hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.22-0.67; P = .001).
Adding rituximab to the first-line chemotherapy significantly improved PFS
compared to chemotherapy alone (HR, 0.26; 95% CI 0.18-0.36; P < .001).
Maintenance rituximab after immunochemotherapy in first-line treatment reduced
the risk for progression by 61% and significantly prolonged the time to
progression (HR, 0.39; 95% CI 0.20-0.73; P < .003). CONCLUSION: The outcomes in
our routinely treated FL patients confirm the benefit of adding rituximab to
chemotherapy and are comparable to the results of pivotal clinical studies. The
outcome of our FL patients was improved in terms of both PFS and OS.
PMID- 26423703
TI - Circulating Levels of Urokinase-Type Plasminogen Activator Receptor and D-Dimer
in Patients With Hematological Malignancies.
AB - BACKGROUND: Patients with cancer exhibit changes in their hemostatic mechanisms.
The D-dimer (D-D) is the most important subproduct of fibrinolysis, and urokinase
plasminogen activator receptor (uPAR) is related to invasiveness and metastases,
and is overexpressed in neoplastic cells. The objective of this study was to
identify in patients with hematological neoplasia, the serum levels of uPAR and D
D, and to determine their effects on outcome. PATIENTS AND METHODS: A cross
sectional study was performed. Clinical and demographic data were obtained from
the clinical chart. Determination of uPAR in serum (pg/L) was performed using an
enzyme-linked immunosorbent assay, and D-D (MUg/dL) using nephelometry. RESULTS:
We included 42 patients (35 with lymphomas). Statistically significant
differences were found in D-D (P < .001) and uPAR (P < .01) between patients and
control participants. Response was an accumulated clinical outcome. We observed
statistical differences between groups (P < .001). D-D was positive in 70% of
cases. CONCLUSION: We found differences in D-D serum levels and soluble uPAR
between control participants and patients with lymphoma. These results indicate
that D-D serum levels and soluble uPAR should be considered biomarkers of
response and survival in patients with lymphoma.
PMID- 26423704
TI - In Silico Design of Highly Selective Mo-V-Te-Nb-O Mixed Metal Oxide Catalysts for
Ammoxidation and Oxidative Dehydrogenation of Propane and Ethane.
AB - We used density functional theory quantum mechanics with periodic boundary
conditions to determine the atomistic mechanism underlying catalytic activation
of propane by the M1 phase of Mo-V-Nb-Te-O mixed metal oxides. We find that
propane is activated by Te?O through our recently established reduction-coupled
oxo activation mechanism. More importantly, we find that the C-H activation
activity of Te?O is controlled by the distribution of nearby V atoms, leading to
a range of activation barriers from 34 to 23 kcal/mol. On the basis of the new
insight into this mechanism, we propose a synthesis strategy that we expect to
form a much more selective single-phase Mo-V-Nb-Te-O catalyst.
PMID- 26423705
TI - Indolent CD8-positive lymphoid proliferation of acral sites: three further cases
of a rare entity and an update on a unique patient.
AB - BACKGROUND: Primary cutaneous indolent CD8-positive lymphoid proliferation is an
emerging entity characterized by slowly enlarging papules and nodules that are
pathologically comprised of clonal nonepidermotropic medium-sized atypical CD8(+)
T-cells. Although the majority of lesions are solitary and located on the ears,
bilateral symmetrical presentations have been described and lesions may arise at
other peripheral or 'acral' sites. Patients follow a benign clinical course and
systemic involvement has not yet been observed. Despite this, some medical
practitioners classify such lesions as peripheral T-cell lymphoma, NOS, a
category implying aggressive disease. OBJECTIVES: We present three cases seen in
our institutions and provide an update on a previously reported unique patient
who continues to develop recurrent and multifocal skin lesions. RESULTS: Systemic
disease progression has not been observed, even in the presence of recurrent and
multifocal cutaneous disease. CONCLUSIONS: Indolent CD8-positive lymphoid
proliferation of acral sites is a distinctive and readily identifiable entity and
should be included in the next consensus revision of cutaneous lymphoma
classification. Although cases described thus far have followed an indolent
clinical course, dermatologists should remain guarded about the prognosis and
full staging and longitudinal observation are recommended until this condition is
better understood.
PMID- 26423707
TI - Liam Smeeth: Still hoping for Olympic gold.
PMID- 26423708
TI - Developing interventions in child and adolescent mental health services: Do we
really know what works for whom?
PMID- 26423706
TI - Monitoring the athlete training response: subjective self-reported measures trump
commonly used objective measures: a systematic review.
AB - BACKGROUND: Monitoring athlete well-being is essential to guide training and to
detect any progression towards negative health outcomes and associated poor
performance. Objective (performance, physiological, biochemical) and subjective
measures are all options for athlete monitoring. OBJECTIVE: We systematically
reviewed objective and subjective measures of athlete well-being. Objective
measures, including those taken at rest (eg, blood markers, heart rate) and
during exercise (eg, oxygen consumption, heart rate response), were compared
against subjective measures (eg, mood, perceived stress). All measures were also
evaluated for their response to acute and chronic training load. METHODS: The
databases Academic search complete, MEDLINE, PsycINFO, SPORTDiscus and PubMed
were searched in May 2014. Fifty-six original studies reported concurrent
subjective and objective measures of athlete well-being. The quality and strength
of findings of each study were evaluated to determine overall levels of evidence.
RESULTS: Subjective and objective measures of athlete well-being generally did
not correlate. Subjective measures reflected acute and chronic training loads
with superior sensitivity and consistency than objective measures. Subjective
well-being was typically impaired with an acute increase in training load, and
also with chronic training, while an acute decrease in training load improved
subjective well-being. SUMMARY: This review provides further support for
practitioners to use subjective measures to monitor changes in athlete well-being
in response to training. Subjective measures may stand alone, or be incorporated
into a mixed methods approach to athlete monitoring, as is current practice in
many sport settings.
PMID- 26423709
TI - Emergency department visits and revisits for nontraumatic dental conditions in
Iowa.
AB - OBJECTIVES: To examine the characteristics associated with emergency department
(ED) utilization in Iowa for nontraumatic dental conditions (NTDCs), and those
associated with having multiple visits to the ED for NTDCs before the Medicaid
expansion program in Iowa. METHODS: State Emergency Department Database for Iowa
was used for 2012, which comprised of all outpatient ED visits in the state.
Logistic regression was used for bivariate and multivariable analyses to model
the odds of visiting the ED for NTDCs, relative to other conditions, and odds of
visiting the ED multiple times relative to a single time in 2012 for NTDCs. The
hospital charges associated with the NTDC ED visits were also examined. RESULTS:
ED visits for NTDCs comprised 1.41% of all ED visits in Iowa during 2012 with a
mean charge of $557. Of the patients presenting for NTDCs in 2012, 17% presented
multiples times. Young adults, Medicaid enrollees or uninsured, and those
residing in metropolitan areas had greater odds of presenting to the EDs for
NTDCs compared with other conditions, and presenting multiple times to EDs for
NTDCs. Those with more chronic conditions also had greater odds of repeatedly
visiting the ED for NTDCs. CONCLUSIONS: Low-income young adults in Iowa rely on
EDs for their dental needs that can have substantial costs. The Dental Wellness
Plan (DWP) is intended to facilitate dental care access by providing dental
coverage to low-income Iowans. This study provides baseline data that will be
used to evaluate the success of DWP in improving access to dental care.
PMID- 26423710
TI - Positive effect of combined exercise training in a model of metabolic syndrome
and menopause: autonomic, inflammatory, and oxidative stress evaluations.
AB - It is now well established that after menopause cardiometabolic disorders become
more common. Recently, resistance exercise has been recommended as a complement
to aerobic (combined training, CT) for the treatment of cardiometabolic diseases.
The aim of this study was to evaluate the effects of CT in hypertensive
ovariectomized rats undergoing fructose overload in blood pressure variability
(BPV), inflammation, and oxidative stress parameters. Female rats were divided
into the following groups (n = 8/group): sedentary normotensive Wistar rats (C),
and sedentary (FHO) or trained (FHOT) ovariectomized spontaneously hypertensive
rats undergoing and fructose overload. CT was performed on a treadmill and ladder
adapted to rats in alternate days (8 wk; 40-60% maximal capacity). Arterial
pressure (AP) was directly measured. Oxidative stress and inflammation were
measured on cardiac and renal tissues. The association of risk factors
(hypertension + ovariectomy + fructose) promoted increase in insulin resistance,
mean AP (FHO: 174 +/- 4 vs. C: 108 +/- 1 mmHg), heart rate (FHO: 403 +/- 12 vs.
C: 352 +/- 11 beats/min), BPV, cardiac inflammation (tumor necrosis factor-alpha
FHO: 65.8 +/- 9.9 vs. C: 23.3 +/- 4.3 pg/mg protein), and oxidative stress
cardiac and renal tissues. However, CT was able to reduce mean AP (FHOT: 158 +/-
4 mmHg), heart rate (FHOT: 303 +/- 5 beats/min), insulin resistance, and
sympathetic modulation. Moreover, the trained rats presented increased nitric
oxide bioavailability, reduced tumor necrosis factor-alpha (FHOT: 33.1 +/- 4.9
pg/mg protein), increased IL-10 in cardiac tissue and reduced lipoperoxidation,
and increased antioxidant defenses in cardiac and renal tissues. In conclusion,
the association of risk factors promoted an additional impairment in metabolic,
cardiovascular, autonomic, inflammatory, and oxidative stress parameters and
combined exercise training was able to attenuate these dysfunctions.
PMID- 26423711
TI - Chronic hypoxia during development does not trigger pathologic remodeling of the
chicken embryonic heart but reduces cardiomyocyte number.
AB - Fetal growth restriction programs an increased risk of cardiovascular disease in
adulthood, but the actual mechanisms of this developmental programming are not
fully understood. Previous studies in mammalian models suggest that hearts of
growth-restricted fetuses have reduced cardiomyocyte number due to reduced
proliferation and premature cardiomyocyte maturation. Chicken embryos incubated
under chronic hypoxia are also growth-restricted, have smaller hearts, and show
signs of cardiac insufficiency posthatching. The aim of the present study was to
investigate how chronic hypoxia (14% O2) during development affects cardiomyocyte
mass and how myocardial structure is altered. Hypoxic incubation reproduced the
well-characterized embryonic growth restriction and an increased ventricle-to
body mass ratio (at E11, E15, E17, and E19) with reduced absolute heart mass only
at E19. Cell density, apoptosis, and cardiomyocyte size were insensitive to
hypoxia at E15 and E19, and no signs of ventricular wall remodeling or myocardial
fibrosis were detected. Bayesian modeling provided strong support for hypoxia
affecting absolute mass and proliferation rates at E15, indicating that the
growth impairment, at least partly, occurs earlier in development. Neither E15
nor E19 hearts contained binucleated cardiomyocytes, indicating that fetal
hypoxia does not trigger early maturation of cardiomyocytes in the chicken, which
contrasts with previous results from hypoxic rat pups. In conclusion, prenatal
hypoxia in the chick embryo results in a reduction in the number of
cardiomyocytes without inducing ventricular remodeling, cell hypertrophy, or
premature cardiomyocyte maturation.
PMID- 26423712
TI - Effect of doxycycline on contralateral canine cranial cruciate ligament rupture.
A prospective randomized clinical trial in 69 dogs.
AB - OBJECTIVE: To evaluate whether doxycycline administered to dogs with unilateral
cranial cruciate ligament rupture (Uni-CCLR) would decrease the risk of
contralateral-CCLR (Co-CCLR). To evaluate predictors for Co-CCLR survival. To
evaluate if a predisposition of Labrador Retrievers to Co-CCLR exists when
compared to other breeds. METHODS: In this prospective randomized controlled
clinical trial, 69 client-owned dogs with Uni-CCLR were randomly assigned to a
doxycycline (group-D: 7.5 mg/kg PO BID x 6 weeks) or non-doxycycline (group-ND:
negative control). Medical and imaging data, time from Uni- to Co-CCLR and to
follow-up were recorded. Statistics included chi-squared test, logistic
regression, Kaplan-Meier survival analysis, log rank test, survival curves, and
frailty model (p <0.05). RESULTS: This study included 32 dogs in group-D, and 37
dogs in group-ND. Median follow-up was 54.5 and 61 months, respectively.
Contralateral CCLR occurred in 53.1% and 48.6% at medians of 20 and 11 months,
respectively. Doxycycline did not significantly decrease the risk of Co-CCLR (p =
0.83). This risk was decreased by 14.2% with each year of age but increased with
each increasing kilogram of body weight and each increasing degree of tibial
plateau angle by 5.4% and 9.7%, respectively. Labrador Retrievers were not
significantly predisposed (p = 0.37). CLINICAL SIGNIFICANCE: At the dose regimen
investigated doxycycline does not decrease the risk for Co-CCLR.
PMID- 26423713
TI - Cystic Tumor of the Intra-Atrial Septum.
PMID- 26423714
TI - Boceprevir for chronic HCV genotype 1 infection in treatment-experienced patients
with severe fibrosis or cirrhosis: The Greek real-life experience.
AB - BACKGROUND: The aim of our study was to evaluate the safety and efficacy of
triple therapy using boceprevir (BOC) with pegylated interferon (pIFN)/ribavirin
(RBV) in chronic hepatitis C (CHC) genotype 1 (G1) treatment-experienced patients
with advanced fibrosis or compensated cirrhosis. METHODS: We report the Greek
experience on the first CHC patients who received BOC-based regimen. From
September 2011 to June 2012, 26 treatment-experienced CHC patients and G1 with
bridging fibrosis or compensated cirrhosis received 48 weeks of BOC+pIFN+RBV
antiviral therapy. Data on complete blood counts and HCV RNA levels were obtained
prior to therapy, at treatment weeks 4, 8, 12, 24, 36, 48 and 24 weeks after the
end of treatment. RESULTS: A full set analysis was performed in 25 of 26
patients. Nine patients (36%) achieved sustained viral response (SVR). Ten
patients (40%) stopped the therapy because of futility rules and 3 (12%) due to
adverse events. Four patients (16%) developed a virological breakthrough (3 of
those presented futility rules as well) and 2 (8%) relapse. All patients who
achieved SVR had G 1b, 6 (67%) were non-cirrhotic and 5 (55%) had >1 log decline
in baseline HCV RNA levels at week 4 of the treatment. There were no deaths,
while two patients were hospitalized due to side effects. CONCLUSION: The triple
therapy with BOC+pIFN+RBV in this cohort of real-life treatment-experienced CHC
G1 patients and advanced liver disease was safe offering cure in the majority of
those who could tolerate and complete treatment under a close monitoring.
PMID- 26423715
TI - Free Triiodothyronine Concentrations are Inversely Associated with Elevated
Carotid Intima-Media Thickness in Middle-Aged and Elderly Chinese Population.
AB - AIM: Increased carotid artery intima media thickness (C-IMT) is an early feature
of atherosclerosis. It has been reported to be altered in patients with thyroid
dysfunction, and the evidence is still controversial. The present study aimed to
explore the relationship between C-IMT and possible variations in thyroid
function in Chinese adults aged 40 years and above. METHODS: A community-based
cross-sectional study was conducted among 2276 non-diabetic participants. Serum
free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating
hormone (TSH) were determined by chemiluminescent microparticle immunoassay.
RESULTS: The prevalence of elevated C-IMT decreased according to FT3 quartiles
(29.8%, 24.3%, 24.2%, and 22.2%, P for trend=0.005). In both univariate and
multivariate linear regression analyses, FT3 levels were inversely associated
with C-IMT (both P values <= 0.002). Multivariate-adjusted logistic regression
analysis showed that high FT3 levels were associated with low prevalent elevated
C-IMT. The adjusted odds ratio for elevated C-IMT was 0.71 (95% confidence
interval, 0.52-0.99, P=0.04) when comparing the highest with the lowest quartile
of FT3. CONCLUSIONS: Serum FT3 levels were inversely associated with elevated C
IMT in middle-aged and elderly Chinese adults without diabetes, independent of
traditional risk factors for atherosclerosis.
PMID- 26423716
TI - Cytochrome P450 Genetic Variants and Their Metabolite Levels Associated with
Plaque Stability in Patients with Ischemic Stroke.
AB - AIM: Cytochrome P450s (CYP450) enzymes regulate inflammation and atherosclerosis
and can affect carotid plaque stability in patients with ischemic stroke (IS).
This study aimed to investigate the association of CYP450 genetic variants with
CYP plasma metabolite levels and plaque stability in patients with IS. METHODS:
Eleven single nucleotide polymorphisms (SNPs) of CYP genes and their plasma
metabolite [20-hydroxyeicosatetraenoic acid (HETE), total epoxyeicosatrienoic
acids (EETs), and dihydroxyeicosatrienoic acids (DiHETEs)] levels were measured
in 396 patients with IS who underwent high-resolution B-mode ultrasound carotid
plaque detection and were stratified into the following groups: non-carotid
plaque and carotid plaque groups. The carotid plaque was further classified into
subgroups of echolucent plaque (ELP) and echogenic plaque (EGP). RESULTS: Among
the 396 patients with IS, 294 cases (74%) had plaques. The frequency of
rs17110453CC, rs751141 GG, and rs9333025 GG genotypes was significantly higher in
patients with plaque than those without plaque. The CC, GG, GG, and GG genotypes
of rs17110453, rs776746, rs751141, and rs9333025 polymorphisms were independently
associated with ELP (OR, 2.62 [1.34-5.26]; OR, 1.89 [1.16-3.58]; OR, 3.12 [1.27
7.13]; and OR, 2.06 [1.34-6.33], respectively). These polymorphisms were also
associated with CYP plasma metabolite levels. Patients with ELP have also shown
significantly higher levels of 20-HETE and DiHETEs, but lower levels of EETs.
CONCLUSIONS: Our data demonstrates that CYP450 SNPs are associated with plasma
CYP450 metabolite levels and echolucent plaques, indicating that these SNPs may
be potential markers for plaque instability.
PMID- 26423717
TI - Waist Circumference is Better Than Other Anthropometric Indices for Predicting
Cardiovascular Disease Risk Factors in Chinese Children--a Cross-Sectional Study
in Guangzhou.
AB - AIM: To determine the best anthropometric index among body mass index (BMI),
waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-stature ratio
(WSR) and to derive optimal thresholds for predicting CVD risk factors in Chinese
children. METHODS: A total of 2563 children aged 8-12 years were recruited in
Guangzhou, China. Anthropometric indices were measured in all participants.
Systolic and diastolic blood pressure (SBP and DBP, respectively), glucose,
triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDLC)
and low-density lipoprotein cholesterol (LDL-C) were measured in a subsample of
1609 children. RESULTS: In partial correlation analyses, the highest coefficients
were found for WC in four risk factors in both genders. The receiver operating
characteristic (ROC) analyses showed that WC was comparably consistent among the
best in predicting BP and risk factor clustering, WC and WSR were the best in
predicting HDL-C and TG in boys; WC, slightly better than BMI, was the best in
distinguishing high BP and risk factor clustering in girls. In contrast, WHR was
consistently the poorest index in both genders. Optimal age- and gender-specific
thresholds to identify individual and clustering risk factors were provided; the
thresholds for WC were 57.4-80.4 cm and 55.8-69.6 cm in boys and girls,
respectively. CONCLUSIONS: WC was the comparatively consistent and best predictor
of CVD risk factors compared with WSR and BMI, although the differences were
small and depended on the type of risk factor and gender, and WHR was
consistently the poorest predictor in Chinese children.
PMID- 26423718
TI - CDH13 Polymorphisms are Associated with Adiponectin Levels and Metabolic Syndrome
Traits Independently of Visceral Fat Mass.
AB - AIM: Visceral fat accumulation contributes to the development of metabolic
syndrome. As visceral fat accumulation increases, adiponectin levels decrease;
therefore, adiponectin provides a link between visceral fat accumulation and
metabolic disorders. Genome-wide association studies (GWASs) have identified
genetic variations in the cadherin 13 (CDH13) gene that are associated with
adiponectin levels. METHODS: We investigated whether single nucleotide
polymorphisms (SNPs) in CDH13 was associated with adiponectin levels and
metabolic syndrome traits independent of the visceral fat area (VFA), as measured
using computed tomography (CT) in 945 Japanese individuals. RESULTS: We found
that three CDH13 SNPs reported by recent GWASs (i.e., rs3865188, rs4783244, and
rs12051272) were significantly associated with higher adiponectin levels (P < 1 *
10 (-14)), even after adjustment for VFA. However, these adiponectin-inducing
alleles of CDH13 SNPs were significantly associated with traits consistent with
deteriorating metabolic symptoms, such as higher fasting insulin, homeostasis
model assessment-insulin resistance (HOMA-IR) scores, and triglycerides and lower
high-density lipoprotein (HDL)-cholesterol levels, similar to increasing VFA and
decreasing adiponectin levels. CONCLUSION: These results suggested that CDH13
SNPs cause an adiponectin-resistant status to compensate for increasing
adiponectin levels and could result in the deterioration of metabolic syndrome
traits.
PMID- 26423720
TI - Exciting opportunities to publish your analytical research: Analytical Chemistry,
ACS Sensors, and the Journal of Proteome Research.
PMID- 26423719
TI - Pteridine-2,4-diamine derivatives as radical scavengers and inhibitors of
lipoxygenase that can possess anti-inflammatory properties.
AB - BACKGROUND: Reactive oxygen species are associated with inflammation implicated
in cancer, atherosclerosis and autoimmune diseases. The complex nature of
inflammation and of oxidative stress suggests that dual-target agents may be
effective in combating diseases involving reactive oxygen species. RESULTS: A
novel series of N-substituted 2,4-diaminopteridines has been synthesized and
evaluated as antioxidants in several assays. Many exhibited potent lipid
antioxidant properties, and some are inhibitors of soybean lipoxygenase, IC50
values extending down to 100 nM for both targets. Several pteridine derivatives
showed efficacy at 0.01 mmol/kg with little tissue damage in a rat model of
colitis. 2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)pteridin-4-amine (18f)
at 0.01 mmol/kg exhibited potent anti-inflammatory activity (reduction by 41%).
CONCLUSION: The 2,4-diaminopteridine core represents a new scaffold for
lipoxygenase inhibition as well as sustaining anti-inflammatory properties.
PMID- 26423721
TI - Cognitive and functional status predictors of delirium and delirium severity
after coronary artery bypass graft surgery: an interim analysis of the
Neuropsychiatric Outcomes After Heart Surgery study.
AB - BACKGROUND: Cognitive and functional impairment increase risk for post-coronary
artery bypass graft (CABG) surgery delirium (PCD), but how much impairment is
necessary to increase PCD risk remains unclear. METHODS: The Neuropsychiatric
Outcomes After Heart Surgery (NOAHS) study is a prospective, observational cohort
study of participants undergoing elective CABG surgery. Pre-operative cognitive
and functional status based on Clinical Dementia Rating (CDR) scale and
neuropsychological battery are assessed. We defined mild cognitive impairment
(MCI) based on either (1) CDR global score 0.5 (CDR-MCI) or (2) performance 1.5
SD below population means on any cognitive domain on neurocognitive battery (MCI
NC). Delirium was assessed daily post-operative day 2 through discharge using the
confusion assessment method (CAM) and delirium index (DI). We investigate whether
MCI - either definition - predicts delirium or delirium severity. RESULTS: So far
we have assessed 102 participants (mean age 65.1 +/- 9; male: 75%) for PCD.
Twenty six participants (25%) have MCI-CDR; 38 (62% of those completing
neurocognitive testing) met MCI-NC criteria. Fourteen participants (14%)
developed PCD. After adjusting for age, sex, comorbidity, and education, MCI-CDR,
MMSE, and Lawton IADL score predicted PCD on logistic regression (OR: 5.6, 0.6,
and 1.5, respectively); MCI-NC did not (OR [95% CI]: 11.8 [0.9, 151.4]). Using
similarly adjusted linear regression, MCI-CDR, MCI-NC, CDR sum of boxes, MMSE,
and Lawton IADL score predicted delirium severity (adjusted R(2): 0.26, 0.13,
0.21, 0.18, and 0.32, respectively). CONCLUSIONS: MCI predicts post-operative
delirium and delirium severity, but MCI definition alters these relationships.
Cognitive and functional impairment independently predict post-operative delirium
and delirium severity.
PMID- 26423722
TI - DMAP: a connectivity map database to enable identification of novel drug
repositioning candidates.
AB - BACKGROUND: Drug repositioning is a cost-efficient and time-saving process to
drug development compared to traditional techniques. A systematic method to drug
repositioning is to identify candidate drug's gene expression profiles on target
disease models and determine how similar these profiles are to approved drugs.
Databases such as the CMAP have been developed recently to help with systematic
drug repositioning. METHODS: To overcome the limitation of connectivity maps on
data coverage, we constructed a comprehensive in silico drug-protein connectivity
map called DMAP, which contains directed drug-to-protein effects and effect
scores. The drug-to-protein effect scores are compiled from all database entries
between the drug and protein have been previously observed and provide a
confidence measure on the quality of such drug-to-protein effects. RESULTS: In
DMAP, we have compiled the direct effects between 24,121 PubChem Compound ID
(CID), which were mapped from 289,571 chemical entities recognized from public
literature, and 5,196 reviewed Uniprot proteins. DMAP compiles a total of 438,004
chemical-to-protein effect relationships. Compared to CMAP, DMAP shows an
increase of 221 folds in the number of chemicals and 1.92 fold in the number of
ATC codes. Furthermore, by overlapping DMAP chemicals with the approved drugs
with known indications from the TTD database and literature, we obtained 982
drugs and 622 diseases; meanwhile, we only obtained 394 drugs with known
indication from CMAP. To validate the feasibility of applying new DMAP for
systematic drug repositioning, we compared the performance of DMAP and the well
known CMAP database on two popular computational techniques: drug-drug-similarity
based method with leave-one-out validation and Kolmogorov-Smirnov scoring based
method. In drug-drug-similarity-based method, the drug repositioning prediction
using DMAP achieved an Area-Under-Curve (AUC) score of 0.82, compared with that
using CMAP, AUC = 0.64. For Kolmogorov-Smirnov scoring based method, with DMAP,
we were able to retrieve several drug indications which could not be retrieved
using CMAP. DMAP data can be queried using the existing C2MAP server or
downloaded freely at: http://bio.informatics.iupui.edu/cmaps CONCLUSIONS:
Reliable measurements of how drug affect disease-related proteins are critical to
ongoing drug development in the genome medicine era. We demonstrated that DMAP
can help drug development professionals assess drug-to-protein relationship data
and improve chances of success for systematic drug repositioning efforts.
PMID- 26423723
TI - SiR-Hoechst is a far-red DNA stain for live-cell nanoscopy.
AB - Cell-permeable DNA stains are popular markers in live-cell imaging. Currently
used DNA stains for live-cell imaging are either toxic, require illumination with
blue light or are not compatible with super-resolution microscopy, thereby
limiting their utility. Here we describe a far-red DNA stain, SiR-Hoechst, which
displays minimal toxicity, is applicable in different cell types and tissues, and
is compatible with super-resolution microscopy. The combination of these
properties makes this probe a powerful tool for live-cell imaging.
PMID- 26423725
TI - Clinical Trials With Mesenchymal Stem Cells: An Update.
AB - In the last year, the promising features of mesenchymal stem cells (MSCs),
including their regenerative properties and ability to differentiate into diverse
cell lineages, have generated great interest among researchers whose work has
offered intriguing perspectives on cell-based therapies for various diseases.
Currently the most commonly used adult stem cells in regenerative medicine, MSCs,
can be isolated from several tissues, exhibit a strong capacity for replication
in vitro, and can differentiate into osteoblasts, chondrocytes, and adipocytes.
However, heterogeneous procedures for isolating and cultivating MSCs among
laboratories have prompted the International Society for Cellular Therapy (ISCT)
to issue criteria for identifying unique populations of these cells.
Consequently, the isolation of MSCs according to ISCT criteria has produced
heterogeneous, nonclonal cultures of stromal cells containing stem cells with
different multipotent properties, committed progenitors, and differentiated
cells. Though the nature and functions of MSCs remain unclear, nonclonal stromal
cultures obtained from bone marrow and other tissues currently serve as sources
of putative MSCs for therapeutic purposes, and several findings underscore their
effectiveness in treating different diseases. To date, 493 MSC-based clinical
trials, either complete or ongoing, appear in the database of the US National
Institutes of Health. In the present article, we provide a comprehensive review
of MSC-based clinical trials conducted worldwide that scrutinizes biological
properties of MSCs, elucidates recent clinical findings and clinical trial phases
of investigation, highlights therapeutic effects of MSCs, and identifies
principal criticisms of the use of these cells. In particular, we analyze
clinical trials using MSCs for representative diseases, including hematological
disease, graft-versus-host disease, organ transplantation, diabetes, inflammatory
diseases, and diseases in the liver, kidney, and lung, as well as cardiovascular,
bone and cartilage, neurological, and autoimmune diseases.
PMID- 26423724
TI - Pre-amyloid oligomers of the proteotoxic RepA-WH1 prionoid assemble at the
bacterial nucleoid.
AB - Upon binding to short specific dsDNA sequences in vitro, the N-terminal WH1
domain of the plasmid DNA replication initiator RepA assembles as amyloid fibres.
These are bundles of single or double twisted tubular filaments in which
distorted RepA-WH1 monomers are the building blocks. When expressed in
Escherichia coli, RepA-WH1 triggers the first synthetic amyloid proteinopathy in
bacteria, recapitulating some of the features of mammalian prion diseases: it is
vertically transmissible, albeit non-infectious, showing up in at least two
phenotypically distinct and interconvertible strains. Here we report B3h7, a
monoclonal antibody specific for oligomers of RepA-WH1, but which does not
recognize the mature amyloid fibres. Unlike a control polyclonal antibody
generated against the soluble protein, B3h7 interferes in vitro with DNA-promoted
or amyloid-seeded assembly of RepA-WH1 fibres, thus the targeted oligomers are on
pathway amyloidogenic intermediates. Immuno-electron microscopy with B3h7 on thin
sections of E. coli cells expressing RepA-WH1 consistently labels the bacterial
nucleoid, but not the large cytoplasmic aggregates of the protein. This
observation points to the nucleoid as the place where oligomeric amyloid
precursors of RepA-WH1 are generated, and suggests that, once nucleated by DNA,
further growth must continue in the cytoplasm due to entropic exclusion.
PMID- 26423726
TI - Mass loss and chemical structures of wheat and maize straws in response to
ultraviolet-B radiation and soil contact.
AB - The role of photodegradation, an abiotic process, has been largely overlooked
during straw decomposition in mesic ecosystems. We investigated the mass loss and
chemical structures of straw decomposition in response to elevated UV-B radiation
with or without soil contact over a 12-month litterbag experiment. Wheat and
maize straw samples with and without soil contact were exposed to three radiation
levels: a no-sunlight control, ambient solar UV-B, and artificially elevated UV-B
radiation. A block control with soil contact was not included. Compared with the
no-sunlight control, UV-B radiation increased the mass loss by 14-19% and the
ambient radiation by 9-16% for wheat and maize straws without soil contact after
12 months. Elevated UV-B exposure decreased the decomposition rates of both wheat
and maize straws when in contact with soil. Light exposure resulted in decreased
O-alkyl carbons and increased alkyl carbons for both the wheat and maize straws
compared with no-sunlight control. The difference in soil contact may influence
the contribution of photodegradation to the overall straw decomposition process.
These results indicate that we must take into account the effects of
photodegradation when explaining the mechanisms of straw decomposition in mesic
ecosystems.
PMID- 26423727
TI - Experimental Validation of Bacillus anthracis A16R Proteogenomics.
AB - Anthrax, caused by the pathogenic bacterium Bacillus anthracis, is a zoonosis
that causes serious disease and is of significant concern as a biological warfare
agent. Validating annotated genes and reannotating misannotated genes are
important to understand its biology and mechanisms of pathogenicity. Proteomics
studies are, to date, the best method for verifying and improving current
annotations. To this end, the proteome of B. anthracis A16R was analyzed via one
dimensional gel electrophoresis followed by liquid chromatography coupled with
tandem mass spectrometry (LC-MS/MS). In total, we identified 3,712 proteins,
including many regulatory and key functional proteins at relatively low
abundance, representing the most complete proteome of B. anthracis to date.
Interestingly, eight sequencing errors were detected by proteogenomic analysis
and corrected by resequencing. More importantly, three unannotated peptide
fragments were identified in this study and validated by synthetic peptide mass
spectrum mapping and green fluorescent protein fusion experiments. These data not
only give a more comprehensive understanding of B. anthracis A16R but also
demonstrate the power of proteomics to improve genome annotations and determine
true translational elements.
PMID- 26423728
TI - Development of a Bayesian response-adaptive trial design for the Dexamethasone
for Excessive Menstruation study.
AB - It is often unclear what specific adaptive trial design features lead to an
efficient design which is also feasible to implement. This article describes the
preparatory simulation study for a Bayesian response-adaptive dose-finding trial
design. Dexamethasone for Excessive Menstruation aims to assess the efficacy of
Dexamethasone in reducing excessive menstrual bleeding and to determine the best
dose for further study. To maximise learning about the dose response, patients
receive placebo or an active dose with randomisation probabilities adapting based
on evidence from patients already recruited. The dose-response relationship is
estimated using a flexible Bayesian Normal Dynamic Linear Model. Several
competing design options were considered including: number of doses, proportion
assigned to placebo, adaptation criterion, and number and timing of adaptations.
We performed a fractional factorial study using SAS software to simulate virtual
trial data for candidate adaptive designs under a variety of scenarios and to
invoke WinBUGS for Bayesian model estimation. We analysed the simulated trial
results using Normal linear models to estimate the effects of each design feature
on empirical type I error and statistical power. Our readily-implemented approach
using widely available statistical software identified a final design which
performed robustly across a range of potential trial scenarios.
PMID- 26423729
TI - Choriocarcinoma-associated pulmonary thromboembolism and pulmonary hypertension:
a case report.
AB - Cases of pulmonary embolism and pulmonary artery hypertension caused by
choriocarcinoma represent a rare clinical emergency. We report a case of a 25
year-old woman who presented with pulmonary embolism and hypertension and died
soon after complete pulmonary embolectomy. A related literature review revealed
that almost all of these patients had previously experienced a spontaneous
abortion (average, 6 months) and were not pregnant.
PMID- 26423730
TI - Circulating thrombospondine-2 in patients with moderate-to-severe chronic heart
failure due to coronary artery disease.
AB - Chronic heart failure (CHF) remains a leading cause of morbidity and mortality.
In the current study, we aimed to evaluate the predictive value of circulating
thrombospondin-2 (TSP-2) for cumulative survival in patients with ischemic CHF
due to coronary artery disease (CAD). The results showed that during a median
follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized
repeatedly. The median circulating levels of TSP-2 in patients who survived and
those who died were 0.63 ng/mL (95%CI=0.55-0.64 ng/mL) and 1.03 ng/mL (95%
CI=0.97-1.07 ng/mL) (P<0.001). Circulating TSP-2 independently predicted all
cause mortality (OR=1.27; 95%CI=1.08-1.59; P=0.002), CHF-related death (OR=1.16;
95%CI=1.02-1.50; P<0.001), and also CHF-related rehospitalization (OR=1.12;
95%CI=1.07-1.25; P<0.001). In conclusion, among CAD patients with symptomatic
CHF, increased circulating TSP-2 is correlated with increased 3-year CHF-related
death, all-cause mortality, and risk for recurrent hospitalization.
PMID- 26423731
TI - Molecular docking simulation analysis of the interaction of dietary flavonols
with heat shock protein 90.
AB - Hsp90 is a major protein involved in the stabilization of various proteins in
cancer cells. The present investigation focused on the molecular docking
simulation studies of flavanols as inhibitors of Hsp90 at the high affinity
adenosine triphosphate (ATP) binding site and analyzed absorption, distribution,
metabolism, excretion and toxicity (ADME-toxicity). The molecular docking
analysis revealed that the flavanols showed competitive inhibition with ATP
molecule at the active site and enhanced pharmacological parameters.
PMID- 26423732
TI - A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity-
and Cancer-Related Genes in Whole Blood of Humans.
AB - BACKGROUND: Preclinical and epidemiologic studies suggest that garlic intake is
inversely associated with the progression of cancer and cardiovascular disease.
OBJECTIVE: We designed a study to probe the mechanisms of garlic action in
humans. METHODS: We conducted a randomized crossover feeding trial in which 17
volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and
5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15
g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was
collected before and 3 h after test meal consumption for gene expression analysis
in whole blood. Illumina BeadArray was used to screen for genes of interest,
followed by real-time quantitative reverse transcriptase-polymerase chain
reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6
cells were treated with a purified garlic extract (0.5 MUL/mL), and mRNA was
measured by qRT-PCR at 0, 3, 6, and 24 h. RESULTS: The following 7 genes were
found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl
hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1alpha
(HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT)
activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1),
oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog
(REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1)
(P < 0.05). The mRNA levels of 5 of the 7 genes that were upregulated in the
human trial were also upregulated in cell culture at 3 and 6 h: AHR, HIF1A, JUN,
OSM, and REL. Fold-increases in mRNA transcripts in cell culture ranged from 1.7
(HIF1A) to 12.1 (JUN) (P < 0.01). OSM protein was measured by ELISA and was
significantly higher than the control at 3, 6, and 24 h (24 h: 19.5 +/- 1.4 and
74.8 +/- 1.4 pg/mL for control and garlic, respectively). OSM is a pleiotropic
cytokine that inhibits several tumor cell lines in culture. CONCLUSION: These
data indicate that the bioactivity of garlic is multifaceted and includes
activation of genes related to immunity, apoptosis, and xenobiotic metabolism in
humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as
NCT01293591.
PMID- 26423733
TI - Metabolically Healthy Obesity Is Not Associated with Food Intake in White or
Black Men.
AB - BACKGROUND: Healthy obese individuals may be protected against adverse health
outcomes. Diet and race might influence healthy obesity, but data on their roles
and interactions on the phenotype are limited. OBJECTIVE: We compared the food
intake of metabolically healthy obese men to those of other weight status
metabolic health phenotypes. METHODS: Men (n = 4855) aged >= 45 y with BMI >=
18.5 kg/m(2) and free of cardiovascular diseases, diabetes, and cancer were
evaluated in a cross-sectional study of the REGARDS (REasons for Geographic And
Racial Differences in Stroke) study cohort. Food intake was assessed with the use
of a food frequency questionnaire. Weight status-metabolic health phenotypes were
defined by using metabolic syndrome (MetS) and homeostasis model assessment of
insulin resistance (HOMA-IR) criteria. Mean differences in food intake among
weight status-metabolic health phenotypes were compared with the use of linear
regression. RESULTS: MetS-defined healthy obesity was present in 44% of white
obese men and 58% of black obese men; the healthy obese phenotype, based on HOMA
IR, was equally prevalent in both white (20%) and black (21%) obese men. Among
white men, MetS-defined healthy and unhealthy obesity were associated with lower
wholegrain bread intake and higher consumption of red meat (P < 0.001), whereas
HOMA-IR-defined healthy and unhealthy obesity were associated with lower red meat
intake (P < 0.0001) compared with healthy normal weight in multivariable-adjusted
analyses that adjusted for sociodemographic, lifestyle, and clinical confounders.
However, results were attenuated and became nonsignificant after further
adjustment for BMI. Healthy and unhealthy overweight, defined by both criteria,
were associated with lower whole grain bread intake (P < 0.001) in all models.
Among black men, weight status-metabolic health phenotypes were not associated
with food intake in all models. CONCLUSION: Healthy obesity in men is not
associated with a healthier diet. Future studies need to consider dietary
patterns, which may better inform the holistic effect of diet on healthy obesity,
in prospective analyses.
PMID- 26423734
TI - Higher Intakes of Fruits and Vegetables, beta-Carotene, Vitamin C, alpha
Tocopherol, EPA, and DHA Are Positively Associated with Periodontal Healing after
Nonsurgical Periodontal Therapy in Nonsmokers but Not in Smokers.
AB - BACKGROUND: Periodontitis is a chronic inflammatory disease and a significant
risk factor for tooth loss. Although a link between diet and periodontal health
exists, the relation between diet and healing after periodontal therapy has yet
to be investigated. OBJECTIVE: The objective was to determine whether higher
intakes of fruits and vegetables or nutrients with antioxidant or anti
inflammatory activity are associated with greater healing, measured as reduced
probing depth (PD), after scaling and root planing (SRP), a cost-effective
treatment to manage periodontal disease and prevent tooth loss. METHODS: Patients
(63 nonsmokers, 23 smokers) with chronic generalized periodontitis who were
undergoing SRP participated. Healing was evaluated based on PD, assessed at
baseline and 8-16 wk after SRP. Intakes of fruits, vegetables, beta-carotene,
vitamin C, alpha-tocopherol, alpha-linolenic acid (ALA), eicosapentaenoic acid
(EPA), and docosahexaenoic acid (DHA) were estimated using the Block 2005 food
frequency questionnaire and a supplement questionnaire. Serum 25-hydroxyvitamin D
concentrations were also measured. PD (% sites >3 mm) was modeled in multiple
linear regression and analysis of covariance by tertile of intake and adjusted
for age, sex, body mass index (BMI), baseline PD, examiner, gingival bleeding,
and study duration. RESULTS: In nonsmokers, PD was associated with fruit and
vegetable, beta-carotene, vitamin C, alpha-tocopherol, EPA, and DHA intakes (P <
0.05). PD was not significantly associated with ALA intake or serum 25
hydroxyvitamin D concentration. Significant associations that included
supplements (beta-carotene, vitamin C, alpha-tocopherol) were attenuated or lost,
depending on the statistical model used. There were no significant associations
within the group of smokers. CONCLUSIONS: Dietary intakes of fruits and
vegetables, beta-carotene, vitamin C, alpha-tocopherol, EPA, and DHA are
associated with reduced PD after SRP in nonsmokers, but not smokers, with chronic
generalized periodontitis. These findings may lead to the development of dietary
strategies to optimize healing after periodontal procedures. This trial was
registered at clinicaltrials.gov as NCT02291835.
PMID- 26423735
TI - Protein-Energy Malnutrition Causes Deficits in Motor Function in Adult Male Rats.
AB - BACKGROUND: Adult protein-energy malnutrition (PEM) often occurs in combination
with neurological disorders affecting hand use and walking ability. The
independent effects of PEM on motor function are not well characterized and may
be obscured by these comorbidities. OBJECTIVE: Our goal was to undertake a
comprehensive evaluation of sensorimotor function with the onset and progression
of PEM in an adult male rat model. METHODS: In Expt. 1 and Expt. 2, male Sprague
Dawley rats (14-15 wk old) were assigned ad libitum access for 4 wk to normal
protein (NP) or low-protein (LP) diets containing 12.5% and 0.5% protein,
respectively. Expt. 1 assessed muscle strength, balance, and skilled walking
ability on days 2, 8, and 27 by bar-holding, cylinder, and horizontal ladder
walking tasks, respectively. In addition to food intake and body weight,
nutritional status was determined on days 3, 9, and 28 by serum acute-phase
reactant and corticosterone concentrations and liver lipids. Expt. 2 addressed
the effect of an LP diet on hindlimb muscle size. RESULTS: PEM evolved over time
in rats consuming the LP diet. Total food intake decreased by 24% compared with
the NP group. On day 28, body weight and serum albumin decreased by 31% and 26%,
respectively, and serum alpha2-macroglobulin increased by 445% (P < 0.05) in the
LP group compared with the NP group. Forelimb dysfunction (173% increase in
adaptive flexed-arm-hang score) developed on day 2 in rats fed the LP diet (P <
0.001), whereas abnormal walking (34% decreased incidence of correct hindlimb
placement) developed by day 27 (P < 0.05). Relative to the NP diet, the LP diet
reduced the cross-sectional area of gastrocnemius medialis (P < 0.05).
CONCLUSIONS: PEM in adult male rats causes a variety of sensorimotor
abnormalities that develop at different stages of malnutrition. This model can be
used in combination with disease models of sensorimotor deficits to examine the
interactions between nutritional status, other treatments, and disease
progression.
PMID- 26423737
TI - Severe and Moderate Acute Malnutrition Can Be Successfully Managed with an
Integrated Protocol in Sierra Leone.
AB - BACKGROUND: Global acute malnutrition (GAM) is the sum of moderate acute
malnutrition (MAM) and severe acute malnutrition (SAM). The use of different
foods and protocols for MAM and SAM treatment can be cumbersome in emergency
settings. OBJECTIVE: Our objective was to determine the recovery and coverage
rates for GAM of an integrated protocol with a single food product, ready-to-use
therapeutic food (RUTF), compared with standard management. METHODS: This was a
cluster-randomized controlled trial in Sierra Leone conducted in 10 centers
treating GAM in children aged 6-59 mo. The integrated protocol used midupper arm
circumference (MUAC) as the criterion for admission and discharge, with a MUAC
<12.5 cm defining malnutrition. The protocol included a decreasing ration of RUTF
and health maintenance messages delivered by peers. Standard therapy treated MAM
with a fortified blended flour and SAM with RUTF and used weight-for-height to
determine admission to the treatment program. Coverage rates were the number of
children who received treatment/number of children in the community eligible for
treatment. RESULTS: Most of the children receiving integrated management had MAM
(774 of 1100; 70%), whereas among those receiving standard management, SAM
predominated (537 of 857; 63%; P = 0.0001). Coverage was 71% in the communities
served by integrated management and 55% in the communities served by standard
care (P = 0.0005). GAM recovery in the integrated management protocol was 910 of
1100 (83%) children and was 682 of 857 (79%) children in the standard therapy
protocol. CONCLUSION: Integrated management of GAM in children is an acceptable
alternative to standard management and provides greater community coverage. This
trial was registered at clinicaltrials.gov as NCT01785680.
PMID- 26423736
TI - Maternal Obesity and Excessive Gestational Weight Gain Are Associated with
Components of Child Cognition.
AB - BACKGROUND: Maternal overweight and obesity affect two-thirds of women of
childbearing age and may increase the risk of impaired child cognition.
OBJECTIVE: Our objective was to test the hypothesis that high/low gestational
weight gain (GWG) and high/low prepregnancy BMI were associated with offspring
intelligence quotient (IQ) and executive function at age 10. METHODS: Mother
infant dyads (n = 763) enrolled in a birth cohort study were followed from early
pregnancy to 10 y postpartum. IQ was assessed by trained examiners with the use
of the Stanford Binet Intelligence Scale-4th edition. Executive function was
assessed by the number of perseverative errors on the Wisconsin Card Sorting Test
and time to complete Part B on the Trail Making Test. Self-reported total GWG was
converted to gestational-age-standardized GWG z score. Multivariable linear
regression and negative binomial regression were used to estimate independent and
joint effects of GWG and BMI on outcomes while adjusting for covariates. RESULTS:
At enrollment, the majority of women in the Maternal Health Practices and Child
Development cohort were unmarried and unemployed, and more than one-half reported
their race as black. The mean +/- SD GWG z score was -0.5 +/- 1.8, and 27% of
women had a pregravid BMI >= 25. The median (IQR) number of perseverative errors
was 23 (17, 29), the mean +/- SD time on Part B was 103 +/- 42.6 s, and 44% of
children had a low average IQ (<= 89). Maternal obesity was associated with 3.2
lower IQ points (95% CI: -5.6, -0.8) and a slower time to complete the executive
function scale Part B (adjusted beta: 12.7 s; 95% CI: 2.8, 23 s) compared with
offspring of normal-weight mothers. Offspring of mothers whose GWG was >+1 SD,
compared with -1 to +1 SD, performed 15 s slower on the executive function task
(95% CI: 1.8, 28 s). There was no association between GWG z score and offspring
composite IQ score (adjusted beta: -0.32; 95% CI: -0.72, 0.10). Prepregnancy BMI
did not modify these associations. CONCLUSIONS: Although GWG may be important for
executive function, maternal BMI has a stronger relation than GWG to both
offspring intelligence and executive function. Our findings contribute to
evidence linking maternal obesity to long-term child outcomes.
PMID- 26423739
TI - Young Children's Food Neophobia Characteristics and Sensory Behaviors Are Related
to Their Food Intake.
AB - BACKGROUND: Food neophobia in children has been associated with poor dietary
variety and nutrient intakes. Underlying characteristics that may predispose a
child to neophobia have not been widely studied. OBJECTIVE: We investigated the
associations between children's food neophobia, sensory sensitivity, and dietary
intake in a diverse sample of typically developing preschoolers. METHODS:
Caregiver reports of children's food neophobia and sensory behaviors (SBs) as
measured by the Food Neophobia Scale and the Sensory Profile, children's observed
weight outcome [body mass index z score (BMIz)], and children's food intake as
estimated from the Block Kids Food Screener were collected at baseline in the
Colorado LEAP (Longitudinal Eating and Physical Activity Study) study of
childhood obesity. Preschool-aged children (n = 249; 136 girls, 113 boys; aged
55.6 +/- 4.7 mo; BMIz = 0.54 +/- 1.14) and caregivers [n = 180; 57 Hispanic, 119
non-Hispanic white (NHW), 4 unknown] participated. Data were analyzed by Pearson
correlations and multivariate hierarchical linear regression analyses. RESULTS:
Lower scores for children's oral sensory characteristics (i.e., more atypical)
were related to higher neophobia ratings (r = -0.53, P < 0.001), and neophobia
was negatively associated with reported vegetable intake (r = -0.31, P = 0.001)
and dietary variety (r = -0.22, P < 0.001). Hispanic caregivers reported more
atypical child SB scores (46.2 +/- 8.8) than did NHW caregivers (50.5 +/- 7.6; P
= 0.006); however, no differences were noted for neophobia and SB scores by
parent income and education or child sex. Neophobia was negatively associated
with vegetable intake and dietary variety (P < 0.001 for both). SBs were
associated with children's energy intake from sugar-sweetened beverages in
bivariate analyses (r = -0.18, P < 0.05); however, in regression models, only
ethnicity was significantly associated with energy from sugar-sweetened beverages
(P < 0.001). Hispanic ethnicity was positively associated with sugar-sweetened
beverage consumption (P < 0.001). CONCLUSIONS: Children's neophobia and sensory
sensitivity may be important in understanding underlying issues related to
limited food acceptance in typically developing young children and for helping
caregivers facilitate healthy dietary intake patterns for their children. This
trial was registered at clinicaltrials.gov as NCT01937481.
PMID- 26423738
TI - Short Maternal Stature Increases Risk of Small-for-Gestational-Age and Preterm
Births in Low- and Middle-Income Countries: Individual Participant Data Meta
Analysis and Population Attributable Fraction.
AB - BACKGROUND: Small-for-gestational-age (SGA) and preterm births are associated
with adverse health consequences, including neonatal and infant mortality,
childhood undernutrition, and adulthood chronic disease. OBJECTIVES: The specific
aims of this study were to estimate the association between short maternal
stature and outcomes of SGA alone, preterm birth alone, or both, and to calculate
the population attributable fraction of SGA and preterm birth associated with
short maternal stature. METHODS: We conducted an individual participant data meta
analysis with the use of data sets from 12 population-based cohort studies and
the WHO Global Survey on Maternal and Perinatal Health (13 of 24 available data
sets used) from low- and middle-income countries (LMIC). We included those with
weight taken within 72 h of birth, gestational age, and maternal height data (n =
177,000). For each of these studies, we individually calculated RRs between
height exposure categories of < 145 cm, 145 to < 150 cm, and 150 to < 155 cm
(reference: >= 155 cm) and outcomes of SGA, preterm birth, and their combination
categories. SGA was defined with the use of both the International Fetal and
Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) birth weight
standard and the 1991 US birth weight reference. The associations were then meta
analyzed. RESULTS: All short stature categories were statistically significantly
associated with term SGA, preterm appropriate-for-gestational-age (AGA), and
preterm SGA births (reference: term AGA). When using the INTERGROWTH-21st
standard to define SGA, women < 145 cm had the highest adjusted risk ratios
(aRRs) (term SGA-aRR: 2.03; 95% CI: 1.76, 2.35; preterm AGA-aRR: 1.45; 95% CI:
1.26, 1.66; preterm SGA-aRR: 2.13; 95% CI: 1.42, 3.21). Similar associations were
seen for SGA defined by the US reference. Annually, 5.5 million term SGA (18.6%
of the global total), 550,800 preterm AGA (5.0% of the global total), and 458,000
preterm SGA (16.5% of the global total) births may be associated with maternal
short stature. CONCLUSIONS: Approximately 6.5 million SGA and/or preterm births
in LMIC may be associated with short maternal stature annually. A reduction in
this burden requires primary prevention of SGA, improvement in postnatal growth
through early childhood, and possibly further intervention in late childhood and
adolescence. It is vital for researchers to broaden the evidence base for
addressing chronic malnutrition through multiple life stages, and for program
implementers to explore effective, sustainable ways of reaching the most
vulnerable populations.
PMID- 26423740
TI - Modeling Demonstrates That Folic Acid Fortification of Whole-Wheat Flour Could
Reduce the Prevalence of Folate Inadequacy in Canadian Whole-Wheat Consumers.
AB - BACKGROUND: Mandatory folic acid fortification of white-wheat flour and selected
other grain products has reduced the prevalence of neural tube defects in Canada;
however, the fortification of whole-wheat flour is not permitted. OBJECTIVE: The
objective of this study was to model the impact of adding folic acid to whole
wheat flour on the folate intake distribution of Canadians. METHODS: Twenty-four
hour dietary recall and supplement intake data (n = 35,107) collected in the 2004
Canadian Community Health Survey 2.2 were used to calculate the prevalence of
folate inadequacy (POFI) and the proportion of folic acid intakes above the
Tolerable Upper Intake Level (UL). In model 1, folic acid was added to whole
wheat flour-containing foods in amounts comparable to those that are mandatory
for white-wheat flour-containing foods. In model 2, a 50% overage of folic acid
fortification was considered. Models 3 and 4 included assessment of folate intake
distributions in adult whole-wheat consumers with or without a fortification
overage. SIDE (Software for Intake Distribution Estimation; Department of
Statistics and Center for Agricultural and Rural Development, Iowa State
University) was used to estimate usual folate intakes. RESULTS: Mean folate
intakes increased by ~ 5% in all sex and age groups when whole-wheat foods were
fortified (models 1 and 2; P < 0.0001). Folic acid fortification of whole-wheat
flour-containing foods did not change the POFI or percentage of intakes above the
UL in the general population, whether in supplement users or nonusers. Among
whole-wheat consumers, the POFI was reduced by 10 percentage points after
fortification of whole-wheat flour-containing foods (95% CIs did not overlap).
The percentage of whole-wheat consumers with intakes above the UL did not change.
CONCLUSION: Although folic acid fortification of whole-wheat flour-containing
foods is unlikely to change the POFI or proportion of folic acid intakes above
the UL in the general Canadian population, this fortification strategy may reduce
the POFI in adult whole-wheat consumers.
PMID- 26423741
TI - Urinary Phytoestrogens Are Associated with Subtle Indicators of Semen Quality
among Male Partners of Couples Desiring Pregnancy.
AB - BACKGROUND: Phytoestrogens have been associated with subtle hormonal changes,
although effects on male fecundity are largely unknown. OBJECTIVE: We evaluated
associations between male urinary phytoestrogen (isoflavone and lignan)
concentrations and semen quality. METHODS: This study was a prospective cohort
study of 501 male partners of couples desiring pregnancy and discontinuing
contraception. Each participant provided up to 2 semen samples that were analyzed
for 35 semen quality endpoints the following day. Linear mixed-effects models
were used to estimate associations between baseline urinary phytoestrogen
concentrations and semen quality parameters, adjusted for age, body mass index
(BMI), research site, and serum lipid and cotinine concentrations. RESULTS: Most
associations between urinary phytoestrogens and semen quality parameters were
null. However, select individual phytoestrogens were associated with semen
quality parameters, with associations dependent on the class of phytoestrogens
and modified by BMI. Specifically, genistein and daidzein were associated with a
lower percentage of normal sperm and increased abnormalities in semen morphology,
with reduced associations observed as BMI increased (P < 0.05) [percentages (95%
CIs) of normal morphology by WHO traditional criteria: genistein, main effect:
5.61% (-9.42%, -1.79%); interaction: 0.19% (0.06%, 0.31%) per log unit increase;
daidzein, main effect: -5.35% (-9.36%, -1.34%); interaction: 0.18% (0.05%, 0.32%)
per log unit increase]. Enterolactone was associated with fewer abnormalities in
semen morphometry and morphology and decreased DNA fragmentation, with reduced
associations observed as BMI increased (P < 0.05) [percentages (95% CIs) of
abnormalities in the neck and midpiece: enterolactone, main effect: -3.35% (
6.51%, -0.19%); interaction: 0.11% (0.01%, 0.21%) per log unit increase].
CONCLUSIONS: These results suggest that male urinary phytoestrogen concentrations
characteristic of the US population may be associated with subtle indicators of
male fecundity and semen quality but were not associated with couple fecundity.
PMID- 26423742
TI - Preventive Effects of Long-Term Supplementation with 2 Nutritious Food
Supplements in Young Children in Niger.
AB - BACKGROUND: In nutritional crises, large-scale preventive distributions of
specialized nutritious foods are recommended to prevent acute and chronic
malnutrition in young children. Among the available specialized nutritious foods,
the World Food Programme and UNICEF recommend lipid-based nutrient supplements
(LNSs) and Super Cereal Plus (SC+). Although the effectiveness of short-term
distributions for prevention of severe acute malnutrition (SAM) is well
documented, evidence for long-term strategies and the role of distribution of
specialized nutritious foods for prevention of stunting is weaker. OBJECTIVE: The
objective of this study was to compare long-term supplementation of LNSs and SC+
on the incidence of acute malnutrition and stunting in young children. METHODS:
We conducted two 15-mo-long supplementation interventions with the use of LNSs
(500 kcal/d) and SC+ (810 kcal/d) and half rations during 5 mo of the nonlean
season, for the prevention of acute malnutrition and stunting in children aged 6
23 mo. The study was designed as a prospective cohort in 11 villages in
Madarounfa, Niger. We compared the incidence of acute malnutrition and stunting
with the use of Cox proportional hazards models and report on sharing and use of
these food supplements. RESULTS: Characteristics of children at baseline were
similar across groups. A total of 1967 children were included in the analysis
(845 in the SC+ group and 1122 in the LNS group). No significant differences in
the incidence of moderate acute malnutrition (SC+ compared with LNS: adjusted HR:
0.79; 95% CI: 0.61, 1.02) or SAM (HR: 0.84; 95% CI: 0.52, 1.34) were found. No
difference in the incidence of stunting (HR: 1.08; 95% CI: 0.95, 1.24) or severe
stunting (HR: 0.94; 95% CI: 0.71, 1.22) over the follow-up period were found.
CONCLUSIONS: These findings in young children in Niger suggest that both products
should be considered when planning preventive distributions and choice of long
term supplementation should be guided by context-specific factors such as
acceptability, cost, and operational feasibility, among others. Additional
research is essential to improving child health. The study was registered at
clinicaltrials.gov as NCT01828814.
PMID- 26423743
TI - Appropriate initial antibiotic therapy in hospitalized patients with gram
negative infections: systematic review and meta-analysis.
AB - BACKGROUND: The rapid global spread of multi-resistant bacteria and loss of
antibiotic effectiveness increases the risk of initial inappropriate antibiotic
therapy (IAT) and poses a serious threat to patient safety. We conducted a
systematic review and meta-analysis of published studies to summarize the effect
of appropriate antibiotic therapy (AAT) or IAT against gram-negative bacterial
infections in the hospital setting. METHODS: MEDLINE, EMBASE, and Cochrane
CENTRAL databases were searched until May 2014 to identify English-language
studies examining use of AAT or IAT in hospitalized patients with Gram-negative
pathogens. Outcomes of interest included mortality, clinical cure, cost, and
length of stay. Citations and eligible full-text articles were screened in
duplicate. Random effect models meta-analysis was used. RESULTS: Fifty-seven
studies in 60 publications were eligible. AAT was associated with lower risk of
mortality (unadjusted summary odds ratio [OR] 0.38, 95 % confidence interval [CI]
0.30-0.47, 39 studies, 5809 patients) and treatment failure (OR 0.22, 95 % CI
0.14-0.35; 3 studies, 283 patients). Conversely, IAT increased risk of mortality
(unadjusted summary OR 2.66, 95 % CI 2.12-3.35; 39 studies, 5809 patients). In
meta-analyses of adjusted data, AAT was associated with lower risk of mortality
(adjusted summary OR 0.43, 95 % CI 0.23-0.83; 6 studies, 1409 patients).
Conversely, IAT increased risk of mortality (adjusted summary OR 3.30, 95 % CI
2.42-4.49; 16 studies, 2493 patients). A limited number of studies suggested
higher cost and longer hospital stay with IAT. There was considerable
heterogeneity in the definition of AAT or IAT, pathogens studied, and outcomes
assessed. DISCUSSION: Using a large set of studies we found that IAT is
associated with a number of serious consequences,including an increased risk of
hospital mortality. Infections caused by drug-resistant, Gram-negative organisms
represent a considerable financial burden to healthcare systems due to the
increased costs associated with the resources required to manage the infection,
particularly longer hospital stays. However, there were insufficient data that
evaluated AAT for the outcome of costs among patients with nosocomialGram
negative infections. CONCLUSIONS: IAT in hospitalized patients with Gram-negative
infections is associated with adverse outcomes. Technological advances for rapid
diagnostics to facilitate AAT along with antimicrobial stewardship, surveillance,
infection control, and prevention is needed.
PMID- 26423745
TI - The Diagnostic and Therapeutic Impact of Point-of-Care Ultrasonography in the
Intensive Care Unit.
AB - PURPOSE: In light of point-of-care ultrasonography's (POCUS) recent rise in
popularity, assessment of its impact on diagnosis and treatment in the intensive
care unit (ICU) is of key importance. METHODS: Ultrasound examinations were
collected through an ultrasound reporting software in 6 multidisciplinary ICU
units from 3 university hospitals in Canada and the United States. This database
included a self-reporting questionnaire to assess the impact of the ultrasound
findings on diagnosis and treatment. We retrieved the results of these
questionnaires and analyzed them in relation to which organs were assessed during
the ultrasound examination. RESULTS: One thousand two hundred and fifteen
ultrasound studies were performed on 968 patients. Intensivists considered the
image quality of cardiac ultrasound to be adequate in 94.7% compared to 99.7% for
general ultrasound ( P < .001). The median duration of a cardiac examination was
10 (interquartile range [IQR] 10) minutes compared to 5 (IQR 8) minutes for a
general examination ( P < .001). Overall, ultrasound findings led to a change in
diagnosis in 302 studies (24.9%) and to a change in management in 534 studies
(44.0%). A change in diagnosis or management was reported more frequently for
cardiac ultrasound than for general ultrasound (108 [37.1%] vs 127 [16.5%], P <
.001) and (170 [58.4%] vs 270 [35.1%], P < .001). Assessment of the inferior vena
cava for fluid status emerged as the critical care ultrasound application
associated with the greatest impact on management. CONCLUSION: Point-of-care
ultrasonography has the potential to optimize care of the critically ill patients
when added to the clinical armamentarium of the intensive care physician.
PMID- 26423744
TI - Trends in hospital and intensive care admissions in the Netherlands attributable
to the very elderly in an ageing population.
AB - INTRODUCTION: The Dutch population is ageing and it is unknown how this is
affecting trends in the percentage of hospital and intensive care unit (ICU)
admissions attributable to patients aged 80 years or older, the very elderly.
METHODS: We present data on the percentage of the very elderly in the general
population and the percentage of hospital admissions attributable to the very
elderly. We subsequently performed a longitudinal cross-sectional study on ICU
admissions from hospitals participating in the National Intensive Care Evaluation
registry for the period 2005 to 2014. We modeled the percentage of adult ICU
admissions and treatment days attributable to the very elderly separately for ICU
admissions following cardiac surgery and other reasons. RESULTS: The percentage
of Dutch adults aged 80 years and older, increased from 4.5 % in 2005 to 5.4 % in
2014 (p-value < 0.0001) and with this ageing of the population, the percentage of
hospital admissions attributable to very elderly increased from 9.0 % in 2005 to
10.6 % in 2014 (p-value < 0.0001). The percentage of ICU admissions following
cardiac surgery attributable to the very elderly increased from 6.7 % in 2005 to
11.0 % in 2014 in nine hospitals (p-value < 0.0001), while the percentage of
treatment days attributable to this group rose from 8.6 % in 2005 to 11.7 % in
2014 (p-value = 0.0157). In contrast, the percentage of very elderly patients
admitted to the ICU for other reasons than following cardiac surgery remained
stable at 13.8 % between 2005 and 2014 in 33 hospitals (p-value = 0.1315). The
number of treatment days attributable to the very elderly rose from 11,810 in
2005 to 15,234 in 2014 (p-value = 0.0002), but the percentage of ICU treatment
days attributable to this group remained stable at 12.0 % (p-value = 0.1429).
CONCLUSIONS: As in many European countries the Dutch population is ageing and the
percentage of hospital admissions attributable to the very elderly rose between
2005 and 2014. However, the percentage of ICU admissions and treatment days
attributable to very elderly remained stable. The percentage of ICU admissions
following cardiac surgery attributable to this group increased between 2005 and
2014.
PMID- 26423746
TI - A cross-sectional study on health differences between rural and non-rural U.S.
counties using the County Health Rankings.
AB - BACKGROUND: By examining 2013 County Health Rankings and Roadmaps data from the
University of Wisconsin and the Robert Wood Johnson Foundation, this paper seeks
to add to the available literature on health variances between United States
residents living in rural and non-rural areas. We believe this is the first study
to use the Rankings data to measure rural and urban health differences across the
United States and therefore highlights the national need to address shortfalls in
rural healthcare and overall health. The data indicates that U.S. residents
living in rural counties are generally in poorer health than their urban
counterparts. METHODS: We used 2013 County Health Rankings data to evaluate
differences across the six domains of interest (mortality, morbidity, health
behaviors, clinical care, social and economic factors, and physical environment)
for rural and non-rural U.S. counties. This is a cross-sectional study employing
chi-square analysis and logit regression. RESULTS: We found that residents living
in rural U.S. counties are more likely to have poorer health outcomes along a
variety of measurements that comprise the County Health Rankings' indexed domains
of health quality. These populations have statistically significantly (p <= 0.05)
lower scores in such areas as health behavior, morbidity factors, clinical care,
and the physical environment. We attribute the differences to a variety of
factors including limitations in infrastructure, socioeconomic differences,
insurance coverage deficiencies, and higher rates of traffic fatalities and
accidents. DISCUSSIONS: The largest differences between rural and non-rural
counties were in the indexed domains of mortality and clinical care. CONCLUSIONS:
Our analysis revealed differences in health outcomes in the County Health
Rankings' indexed domains between rural and non-rural U.S. counties. We also
describe limitations and offer commentary on the need for more uniform
measurements in the classification of the terms rural and non-rural. These
results can influence practitioners and policy makers in guiding future research
and when deciding on funding allocation.
PMID- 26423747
TI - Epidemiology and associated radiographic spinopelvic parameters of symptomatic
degenerative lumbar scoliosis: are radiographic spinopelvic parameters associated
with the presence of symptoms or decreased quality of life in degenerative lumbar
scoliosis?
AB - OBJECTIVES: To investigate the epidemiology of radiographic degenerative lumbar
scoliosis (DLS) and symptomatic DLS and clarify the impact of radiographic
spinopelvic parameters on the presence of symptoms and quality of life (QOL) in
DLS subjects. METHODS: We obtained the age, gender, screening for chronic low
back pain (CLBP) and lumbar spinal stenosis (LSS), QOL assessments and X-rays of
the thoracolumbar spine from 254 patients from the general population for this
study. The prevalence of DLS and symptomatic DLS were estimated and factors
associated with symptoms, and the QOL in the DLS subjects was analysed. RESULTS:
The prevalence of radiographic and symptomatic DLS was 19.2 and 7.8 %,
respectively. A female gender (p = 0.018) and decreased sacral slope (p = 0.025)
were associated with the presence of CLBP in the DLS subjects. A higher age was
also associated with the presence of LSS in these subjects (p = 0.007), whereas
the Cobb angle was found to be close the limit for significance (p = 0.063). The
sacro-femoral-pubic angle and Cobb angle correlated with the EuroQol-5 dimensions
utility score (r = 0.314, p = 0.014) and EuroQol-visual analogue scale score (r =
-0.291, p = 0.043), respectively. Lumbar lordosis and body mass index correlated
with the lumbar function (r = 0.285, p = 0.047) and visual analogue scale for leg
pain (r = 0.328, p = 0.022) on the Japanese Orthopaedic Association Back Pain
Questionnaire, respectively. CONCLUSIONS: The prevalence of radiographic DLS in
this study was approximately 20 % and roughly 40 % of the DLS subjects had
symptoms. Some spinopelvic parameters may impact the occurrence of symptoms and
the QOL in DLS subjects.
PMID- 26423748
TI - Radiographic measurement error of the scoliotic curve angle depending on
positioning of the patient and the side of scoliotic curve.
AB - BACKGROUND: The Cobb angle measurement is well established for the measurement of
coronal deformity aspect of scoliotic curves. The effect of positional
differences in relation to the apex side of the scoliosis is not yet fully
quantified. While theoretically plausible that positioning error with rotation
toward the apex of the scoliosis would decrease the Cobb angle, the relations are
not investigated yet and were object of this study. MATERIALS AND METHODS:
Multiple measurements of the Cobb angle were performed, while turning a spine
pelvic cadaveric specimen with a right-sided thoracic scoliosis of 47 degrees
(in neutral position) from 45 degrees to -45 degrees in steps of 5 degrees
using biplanar radiography. Statistical methods were applied to find the critical
position, in which measurement errors potentially become clinically relevant
(Cobb angle deviation >5 degrees ). RESULTS: Turning the specimen to the right
(toward the apex of the scoliosis) produced during the first -15 degrees of
rotation, a Cobb angle ranging from 47 degrees to 45 degrees . At -20 degrees ,
the Cobb angle was 42 degrees , at -25 degrees rotation 37 degrees and at -30
degrees rotation 36 degrees . Above -30 degrees rotation, the measured Cobb
angle decreased to 36 degrees (77 % of the original Cobb angle). No relevant
differences were found by rotating the specimen to the left (away from the apex)
(47 degrees at neutral rotation and 44 degrees at maximal error rotation of +45
degrees ). CONCLUSION: The influence of rotational misplacement of the patient at
the time of image acquisition on Cobb angle measurements is negligible for a
rotational misplacement of +/-20 degrees of rotation for a idiopathic right
sided thoracic scoliosis of 47 degrees . Over 20 degrees of rotational
misplacement of the patient toward the apex of the scoliosis falsely decreases
the Cobb angle.
PMID- 26423749
TI - Celiac disease detection in hypothyroid patients requiring elevated thyroid
supplementation: A prospective cohort study.
AB - BACKGROUND: Celiac disease (CD) is associated with hypothyroidism, but the
disease prevalence is not thought to be great enough to warrant testing all
hypothyroid patients. We hypothesized that hypothyroid patients with concomitant
CD would require elevated doses of levothyroxine, and there is a threshold daily
dose, above which, hypothyroid patients should be tested for CD. METHODS:
Hypothyroid patients presenting to the endoscopy or endocrinology clinics at the
University of Vermont Medical Center were included. Patients were categorized by
whether or not they required >=125mcg/day of levothyroxine. A serum tissue
transglutaminase (tTG) was performed on enrolled patients. Patients with an
elevated serum tTG underwent endoscopy with duodenal biopsies. Symptoms were
assessed by the Gastrointestinal Symptom Rating Scale. RESULTS: Overall, 500
patients were enrolled and 29% (144 patients) required >=125mcg/day of
levothyroxine. CD was detected in 9 patients. The prevalence of CD ranged from
1.8% in our entire cohort to 12.5% in patients requiring >=200mcg/day of
levothyroxine. Eight patients with CD (89%) required >=125mcg/day of
levothyroxine. Patients who required >=125mcg/day of levothyroxine had a
significantly increased risk of CD (p<0.001). CD was detected in 5.6% of patients
requiring >=125mcg/day of levothyroxine. CONCLUSIONS: Hypothyroid patients
requiring elevated daily doses of levothyroxine are more likely to have CD.
Hypothyroid patients requiring >=125mcg/day of levothyroxine should undergo
serologic testing for CD.
PMID- 26423751
TI - RETRACTED ARTICLE: Net Fluorescein Flux Across Corneal Endothelium Suggests Fluid
Transport is Driven by Electroosmosis.
PMID- 26423750
TI - Understanding low colorectal cancer screening uptake in South Asian faith
communities in England--a qualitative study.
AB - BACKGROUND: Colorectal cancer screening uptake within the South Asian population
in England is approximately half that of the general population (33 % vs 61 %),
and varies by Muslim (31.9 %), Sikh (34.6 %) and Hindu (43.7 %) faith background.
This study sought to explore reasons for low uptake of CRC screening in South
Asian communities and for the variability of low uptake between three faith
communities; and to identify strategies by which uptake might be improved.
METHODS: We interviewed 16 'key informants' representing communities from the
three largest South Asian faith backgrounds (Islam, Hinduism and Sikhism) in
London, England. RESULTS: Reasons for low colorectal cancer screening uptake were
overwhelmingly shared across South Asian faith groups. These were: limitations
posed by written English; limitations posed by any written language; reliance on
younger family members; low awareness of colorectal cancer and screening; and
difficulties associated with faeces. Non-written information delivered verbally
and interactively within faith or community settings was preferred across faith
communities. CONCLUSIONS: Efforts to increase accessibility to colorectal cancer
screening in South Asian communities should use local language broadcasts on
ethnic media and face-to-face approaches within community and faith settings to
increase awareness of colorectal cancer and screening, and address challenges
posed by written materials.
PMID- 26423752
TI - Health solutions for the poor.
AB - The International Union Against Tuberculosis and Lung Disease (The Union) is the
oldest international non-governmental organisation involved in the fight against
tuberculosis. In 2008, the Institute of The Union was challenged to think boldly
about the future and to develop a diverse work portfolio covering a wide spectrum
of lung health and other disease-related problems. The vision adopted by The
Union at that time was 'Health solutions for the poor'. More recently, there has
been lengthy debate about the need for the Union to concentrate just on its core
mandate of tuberculosis and lung health and for the Union's vision to reflect
this narrower spectrum of activity as 'Lung health solutions for the poor'. In
this viewpoint article we outline our reasons for believing that this narrower
vision is incompatible with The Union's mission statement, and we argue that
making such a change would be a mistake.
PMID- 26423753
TI - Measles in the Democratic Republic of Congo: an urgent wake-up call to adapt
vaccination implementation strategies.
AB - All countries in Africa have made a commitment to eliminate measles by 2020. This
is laudable, as measles elimination will have a crucial impact on reducing
childhood mortality. An important operational challenge is the resurgence of
measles outbreaks in a number of countries; one of the main reasons for this is
that many children are being missed by vaccination programmes. In the Democratic
Republic of Congo (DRC), outbreaks continue unabated despite repeated vaccination
campaigns and high reported coverage by the Ministry of Health. This paper brings
into question the effectiveness of the current approach and the need for better
reflection on bottlenecks and strategies that can address this issue. If we are
to eliminate measles by 2020, there will be a need for impetus, a need for
decisive action to reach that goal and prevent unnecessary childhood deaths in
countries such as the DRC.
PMID- 26423754
TI - Childhood immunisation in Bungoma County, Kenya, from 2008 to 2011: need for
improved uptake.
AB - Uptake of immunisations in children aged 1-2 years in Bungoma County, Kenya, was
determined as part of the 6-monthly Health and Demographic Surveillance System
surveys. A total of 2699 children were assessed between 2008 and 2011. During
this time period, full immunisation declined significantly from 84% to 58%, and
measles vaccine declined uptake from 89% to 60% (P < 0.001). Each year there was
a significant fall-off for the third doses of the oral polio and pentavalent
vaccines (P < 0.001). These findings are of concern, as low immunisation coverage
may lead to vaccine-preventable disease outbreaks. Further investigations into
the reasons for declining immunisation trends are required.
PMID- 26423755
TI - Do non-monetary incentives for pregnant women increase antenatal attendance among
Ethiopian pastoralists?
AB - In a pastoralist setting in Ethiopia, we assessed changes in attendance between
the first and subsequent antenatal care (ANC) visits following the implementation
of non-monetary incentives in a primary health care centre over a 3-year period
from October 2009 to September 2012. Incentives included the provision of a bar
of soap, a bucket, a mosquito net, sugar, cooking oil, a jerrycan and a delivery
kit. The first ANC visits increased by 48% in the first year to 60% in the
second. Subsequent visits did not show a similar pattern due to ruptures in
incentive stocks. Incentives appear to increase ANC attendance; however, ruptures
in stock should be avoided to sustain the effect.
PMID- 26423756
TI - Active and passive case detection strategies for the control of leishmaniasis in
Bangladesh.
AB - SETTING: Two subdistricts in Bangladesh, Fulbaria and Trishal, which are
hyperendemic for leishmaniasis. OBJECTIVE: To determine 1) the numbers of
patients diagnosed with visceral leishmaniasis (VL) and post-kala azar dermal
leishmaniasis (PKDL) using an active case detection (ACD) strategy in Fulbaria
and a passive case detection (PCD) strategy in Trishal, and 2) the time taken
from symptoms to diagnosis in the ACD subdistrict. DESIGN: A cross-sectional
descriptive study of patients diagnosed from May 2010 to December 2011. The ACD
strategy involved community education and outreach workers targeting households
of index patients using symptom-based screening and rK-39 tests for suspected
cases. RESULTS: In the ACD subdistrict (Fulbaria) and PCD sub-district (Trishal),
respectively 1088 and 756 residents were diagnosed with VL and 1145 and 37 with
PKDL. In the ACD subdistrict, the median time to diagnosis for patients directly
referred by outreach workers or self-referred was similar, at 60 days for VL and
respectively 345 and 360 days for PKDL. CONCLUSION: An ACD strategy at the
subdistrict level resulted in an increased yield of VL and a much higher yield of
PKDL. As PKDL acts as a reservoir for infection, a strategy of ACD and treatment
can contribute to the regional elimination of leishmaniasis in the Indian sub
continent.
PMID- 26423757
TI - Providing a gateway to prevention and care for the most at-risk populations in
Bhutan: is this being achieved?
AB - SETTING: Two free-standing urban human immunodeficiency virus (HIV) testing and
counselling (HCT) centres in Bhutan offering services to the general population
and targeting the most at-risk populations (MARPs). OBJECTIVES: To assess the
trend in testing for HIV, hepatitis B and syphilis in both the general population
and MARPs, and to determine if sociodemographic and risk behaviour
characteristics are associated with HIV, hepatitis B and syphilis seropositivity.
DESIGN: Cross-sectional study using client records, 2009 - 2012. RESULTS: Of 7894
clients, 3009 (38%) were from the general population, while 4885 (62%) were from
MARPs. Over the 4-year period, testing declined progressively among the general
population, while it increased or remained static for MARPs. Of 4885 MARPs,
seropositivity was respectively 0.7%, 1.3% and 1.2% for HIV, hepatitis B and
syphilis. Female sex workers (FSWs) (relative risk [RR] 4.4, P = 0.03) and
partners of person living with HIV (RR 25.9, P < 0.001) had a higher risk of
being HIV-positive. FSWs had also a greater risk of being syphilis-positive (RR
9.1, P < 0.001). CONCLUSION: The increase in uptake of HCT services by MARPs is a
welcome finding; however, the relatively static trends call for the introduction
of community outreach approaches. The critical gateway being provided to MARPs is
an 'opportunity' for the expansion of the current service package.
PMID- 26423758
TI - Retention and HIV seroconversion among drug users on methadone maintenance
treatment in Yunnan, China.
AB - SETTING: Thirteen methadone maintenance treatment (MMT) clinics across Yunnan,
the province with the highest human immunodeficiency virus (HIV) burden in China.
OBJECTIVES: To determine, among HIV-negative participants on MMT, the proportion
lost to follow-up (defined as those who missed the 6-monthly follow-up
examination), factors associated with loss to follow-up (LFU), HIV seroconversion
rate and factors associated with seroconversion. DESIGN: Prospective cohort study
from October 2008 to April 2011. All participants were administered a pre-tested
structured questionnaire to capture associated factors and offered HIV testing
every 6 months. chi(2) test and log-binomial regression were used for data
analysis. RESULTS: Of 1146 participants, 541 (47%) were lost to follow-up in 2.5
years. Factors associated with higher LFU proportion include <6 months of
previous MMT, inconvenient location of the MMT clinic and average methadone dose
?60 mg/day, with adjusted relative risks (RRs) of respectively 1.4 (95%CI 1.2
1.5), 1.2 (95%CI 1.0-1.4) and 1.1 (95%CI 1.0-1.3). The overall HIV seroconversion
rate was 6.6 (95%CI 3.7-11.0) per 1000 person-years. Not living with a partner
contributed to higher HIV rates, with an adjusted RR of 3.6 (95%CI 1.0-12.8).
CONCLUSION: The retention rate of MMT participants in Yunnan was not
satisfactory. Decentralising service delivery in the community and making
directly observed treatment more convenient has the potential to improve
retention.
PMID- 26423759
TI - Infection control in households of drug-resistant tuberculosis patients co
infected with HIV in Mumbai, India.
AB - BACKGROUND: Mumbai has a population of 21 million, and an increasingly recognised
epidemic of drug-resistant tuberculosis (DR-TB). OBJECTIVE: To describe TB
infection control (IC) measures implemented in households of DR-TB patients co
infected with the human immunodeficiency virus (HIV) under a Medecins Sans
Frontieres programme. METHODS: IC assessments were carried out in patient
households between May 2012 and March 2013. A simplified, standardised assessment
tool was utilised to assess the risk of TB transmission and guide interventions.
Administrative, environmental and personal protective measures were tailored to
patient needs. RESULTS: IC assessments were carried out in 29 houses. Measures
included health education, segregating sleeping areas of patients, improving
natural ventilation by opening windows, removing curtains and obstacles to air
flow, installing fans and air extractors and providing surgical masks to patients
for limited periods. Environmental interventions were carried out in 22 houses.
CONCLUSIONS: TB IC could be a beneficial component of a comprehensive TB and HIV
care programme in households and communities. Although particularly challenging
in slum settings, IC measures that are feasible, affordable and acceptable can be
implemented in such settings using simplified and standardised tools. Appropriate
IC interventions at household level may prevent new cases of DR-TB, especially in
households of patients with a lower chance of cure.
PMID- 26423760
TI - The trend of tuberculosis cases over 60 years in Fiji's largest treatment centre:
1950-2010.
AB - SETTING: P J Twomey Hospital, National Tuberculosis Programme, Fiji. OBJECTIVES:
To review the trend in numbers of tuberculosis (TB) cases registered each year
from 1950 to 2010 at P J Twomey Hospital, Fiji's largest TB treatment centre and
central TB unit, and to consider trends in the context of key TB control events
in Fiji. DESIGN: Descriptive study of data from medical records and TB registers,
including age, sex, ethnicity, TB diagnosis and smear result. RESULTS: Between
1950 and 2010, 14 616 cases were registered at P J Twomey Hospital. Of these, 58%
were male, 70% were indigenous Fijians (i-taukei) and 64% were aged 15-49 years.
The caseload dropped sharply in the 1960s, and has fallen steadily since 1990.
Smear results were available for the majority of cases (91%). Between 1950 and
1985, smear-positive cases accounted for 19% of cases overall; this increased to
41% after 1985 following laboratory training. The numbers of sputum smear
positive cases recorded each year has been increasing in the last decade.
CONCLUSION: There have been marked changes in TB caseload over the last 60 years
at Fiji's largest TB treatment centre. The recent increase in smear-positive
cases while total TB cases have been falling needs further evaluation.
PMID- 26423761
TI - Using tuberculosis patient characteristics to predict future cases with matching
genotype results.
AB - SETTING: United States. BACKGROUND: It is unknown whether tuberculosis (TB) case
or patient characteristics can predict the likelihood of future related TB cases.
OBJECTIVE: To estimate the likelihood for future related cases, i.e., cases with
matching TB genotypes within the same county diagnosed within the 2 years
following the year of reporting of each included case. DESIGN: We considered all
TB cases with genotyping results reported in the United States during 2004-2010.
Predictive scores were calculated based on patient characteristics by dividing
the number of patients who were not the last case in a county-level TB genotype
cluster by the total number of patients. RESULTS: Overall, there was a 30.8%
chance that a future related case would be detected during the 2 years following
the report year of any given case. Future related cases were detected in 34.7% of
instances following the diagnosis of smear-positive cases, 51.9% of instances
following the diagnosis of a homeless patient and 45.2% of instances following
the diagnosis of a patient who reported substance abuse. Predictive scores ranged
by race (White 13.9%, Native Hawaiian 43.8%) and age group (?65 years 13.1%, 0-4
years 43%), and were higher for US-born patients. CONCLUSIONS: Behavioral and
sociodemographic factors can help predict the likelihood of future related cases
and can be used to prioritize contact investigations.
PMID- 26423762
TI - Effectiveness of reporting on latent tuberculous infection in Massachusetts, 2006
2008.
AB - Massachusetts is one of five states that mandate the reporting of latent
tuberculous infection (LTBI). We assessed 2006-2008 Massachusetts surveillance
data for LTBI to describe the system and examine the characteristics of persons
with LTBI. Over 3 years, 15 301 LTBI cases were reported (4742-5398/year). Among
those with known country of birth (n = 11 655), 9983 (85.7%) were foreign-born.
Substantial under-ascertainment and/or under-reporting appear likely; mandatory
reporting does not appear sufficient for LTBI detection. Enhanced targeted
testing, active LTBI surveillance, or laboratory-based surveillance may be needed
to eliminate tuberculosis disease in the United States.
PMID- 26423763
TI - Does task shifting in tuberculosis microscopy services to non-certified
technicians in Afghanistan affect quality?
AB - SETTING: Tuberculosis microscopy centres in 30 provinces in Afghanistan.
OBJECTIVE: To compare the quality of sputum smear examinations in microscopy
centres with microscopists who are fully certified as laboratory technicians with
those performed in centres with technicians who do not have such certification
(high school graduates). DESIGN: Cross-sectional record review of sputum smear
microscopy slides examined by technicians and cross-checked by trained assessors
as part of routine external quality assurance between July and September 2009.
RESULTS: Of 129 non-certified technicians, 118 (91%) were stationed in rural
health centres compared with 217/257 (84%) certified technicians. From 386
microscopy centres, 7313 slides were cross-checked. Of 257 microscopy centres
with certified technicians, 42 (16%) had at least one slide with a major error
compared to 23 (18%) of 129 microscopy centres staffed with non-certified
technicians. The difference was not statistically significant (OR 1.11, 95%CI
0.64-1.94). The number of slides showing major errors was also similar between
the centres with both certified and non-certified technicians. CONCLUSION: This
study confirms the deployment of non-certified microscopy technicians to
peripheral health centres throughout the country and that their performance with
sputum smear microscopy is similar to that of certified technicians with 3 years
of training.
PMID- 26423764
TI - Screening retreatment tuberculosis patients for drug resistance in mid-west
Nepal: how well are we doing?
AB - SETTING: Multidrug-resistant tuberculosis (MDR-TB, defined as resistance to
isoniazid and rifampicin) is poorly detected in Nepal; one reason may be poor
functioning of culture and drug susceptibility testing (CDST) services for
retreatment tuberculosis (TB) patients. OBJECTIVES: To determine, among
retreatment TB patients in mid-west Nepal, 1) the number of patients registered
for treatment between July 2011 and July 2012; 2) the number submitting sputum
specimens for CDST to the Central Reference Laboratory (CRL), Kathmandu, along
with the results; and 3) the length of time for submission and receipt of
specimens. DESIGN: Retrospective cohort study involving the review of treatment
and laboratory registers from the Nepalgunj TB Referral Centre and the CRL.
RESULTS: Of 431 retreatment patients, 66 (15%) submitted sputum samples, of which
63 reached the CRL. Of these, 39 (62%) were culture-positive; 13 (33%) patients
had MDR-TB. The CDST results of 19 patients were received back at the TB Referral
Centre. The median turnaround time from sending specimens to receipt of results
at the TB Referral Centre was 119 days. CONCLUSION: Less than 10% of retreatment
TB patients in mid-West Nepal had CDST results recorded, leading to the
underdiagnosis of MDR-TB in the region. Urgent solutions are needed to rectify
this problem.
PMID- 26423765
TI - Sex-related trends in non-conversion of new smear-positive tuberculosis patients
in the Free State, South Africa.
AB - SETTING: Free State Province, South Africa. OBJECTIVE: To examine sex-specific
trends in 2-month sputum smear non-conversion in new sputum smear-positive
tuberculosis (TB) cases during a period when the DOTS strategy was operative.
DESIGN: A retrospective cohort study of TB cases registered between 2003 and 2009
was conducted. Non-conversion was indicated by a positive 2-month sputum smear
result. Descriptive and generalised linear model analyses were performed and sex
specific trends in 2-month sputum smear non-conversion rates estimated. RESULTS:
Overall, 2-month sputum smear non-conversion rates were 12.5% in males and 9.3%
in females. Non-conversion was significantly associated with age in males (P <
0.001). Non-conversion rates declined significantly between 2003 and 2009: from
15.9% to 10.8% in males (P < 0.001) and from 12.0% to 6.6% in females (P <
0.001). The average rate of decline of non-conversion was higher among females
(1.0%, 95%CI 0.8-1.2) than among males (0.8%, 95%CI 0.5-1.0). By 2009, males had
a 60% higher risk of non-conversion than females (RR 1.60, CI 1.37-1.86).
CONCLUSION: The decline in the trend of 2-month sputum smear non-conversion
confirms the relative success of the DOTS strategy in TB control, with better
performance among females than males. Interventions should consider the sex and
age of patients to improve the 2-month sputum smear-conversion rate.
PMID- 26423766
TI - Activation of the AMPK-ULK1 pathway plays an important role in autophagy during
prion infection.
AB - AMPK is a serine/threonine protein kinase that acts as a positive regulator of
autophagy, by phosphorylating ULK1 at specific sites. A previous study
demonstrated activation of the macroautophagic system in scrapie-infected
experimental rodents and in certain human prion diseases, in which the essential
negative regulator mTOR is severely inhibited. In this study, AMPK and ULK1 in
the brains of hamsters infected with scrapie strain 263 K and in the scrapie
infected cell line SMB-S15 were analysed. The results showed an up-regulated
trend of AMPK and AMPK-Thr172, ULK1 and ULK1-Ser555. Increases in brain AMPK and
ULK1 occurred at an early stage of agent 263 K infection. The level of
phosphorylated ULK1-Ser757 decreased during mid-infection and was only negligibly
present at the terminal stage, a pattern that suggested a close relationship of
the phosphorylated protein with altered endogenous mTOR. In addition, the level
of LKB1 associated with AMPK activation was selectively increased at the early
and middle stages of infection. Knockdown of endogenous ULK1 in SMB-S15 cells
inhibited LC3 lipidation. These results showed that, in addition to the
abolishment of the mTOR regulatory pathway, activation of the AMPK-ULK1 pathway
during prion infection contributes to autophagy activation in prion-infected
brain tissues.
PMID- 26423767
TI - What Ethical Issues Really Arise in Practice at an Academic Medical Center? A
Quantitative and Qualitative Analysis of Clinical Ethics Consultations from 2008
to 2013.
AB - As the field of clinical ethics consultation sets standards and moves forward
with the Quality Attestation process, questions should be raised about what
ethical issues really do arise in practice. There is limited data on the type and
number of ethics consultations conducted across different settings. At Loyola
University Medical Center, we conducted a retrospective review of our ethics
consultations from 2008 through 2013. One hundred fifty-six cases met the
eligibility criteria. We analyzed demographic data on these patients and
conducted a content analysis of the ethics consultation write-ups coding both the
frequency of ethical issues and most significant, or key, ethical issue per case.
Patients for whom ethics consultation was requested were typically male (55.8 %),
white (57.1 %), between 50 and 69 years old (38.5 %), of non-Hispanic origin
(85.9 %), and of Roman Catholic faith (43.6 %). Nearly half (47.4 %) were in the
intensive care unit and 44.2 % died in the hospital. The most frequent broad
ethical categories were decision-making (93.6 %), goals of care/treatment (80.8
%), and end-of-life (73.1 %). More specifically, capacity (57.1 %), patient's
wishes/autonomy (54.5 %), and surrogate decision maker (51.3 %) were the most
frequent particular ethical issues. The most common key ethical issues were
withdrawing/withholding treatment (12.8 %), patient wishes/autonomy (12.2 %), and
capacity (11.5 %). Our findings provide additional data to inform the training of
clinical ethics consultants regarding the ethical issues that arise in practice.
A wider research agenda should be formed to collect and compare data across
institutions to improve education and training in our field.
PMID- 26423768
TI - A ventilation technique for oxygenation and carbon dioxide elimination in CPR:
Continuous insufflation of oxygen at three levels of pressure in a pig model.
AB - AIM: Pulmonary ventilation remains an important part of cardiopulmonary
resuscitation, affecting gas exchange and haemodynamics. We designed and studied
an improved method of ventilation for CPR, constructed specifically to support
both gas exchange and haemodynamics. This method uses continuous insufflation of
oxygen at three levels of pressure, resulting in tri-level pressure ventilation
(TLPV). We hypothesized that TLPV improves gas exchange and haemodynamics
compared to manual gold standard ventilation (GSV). METHODS: In 14 pigs,
ventricular fibrillation was induced and automated CPR performed for 10 min with
either TLPV or GSV. After defibrillation, CPR was repeated with the other
ventilation method. Gas exchange and haemodynamics were monitored. Data are
presented as mean+/-standard error of the mean. RESULTS: TLPV was superior to GSV
for PaO2 (163+/-36 mmHg difference; P=0.001), and peak AWP (-20+/-2 cmH2O
difference; P=0.000) and higher for mean AWP (8+/-0.2 cmH2O difference; P=0.000).
TLPV was comparable to GSV for CPP (5+/-3 mmHg difference; P=0.012), VCO2 (0.07+/
0.3 mL/min/kg difference; P=0.001), SvO2 (4+/-3%-point; P=0.001), mean carotid
flow (-0.5+/-4 mL/min difference; P=0.016), and pHa (0.00+/-0.03 difference;
P=0.002). The PaCO2 data do not provide a conclusive result (4+/-4 mmHg
difference). CONCLUSION: We conclude that the ventilation strategy with a tri
level pressure cycle performs comparable to an expert, manual ventilator in an
automated-CPR swine model.
PMID- 26423771
TI - The arduous task of differentiating takotsubo syndrome from myocardial infarction
with normal coronary arteries.
PMID- 26423769
TI - Immunotherapy in Sarcoma: Future Horizons.
AB - Immunologic approaches to cancer are over a century old. Over the years, the
strategy has been fine-tuned from inciting infections in subjects to inhibiting
negative regulatory signals from the innate immune system. Sarcomas are among the
first tumors to be considered for immune interventions. From Coley's toxin to
cytokine-based therapies to adoptive cell therapy, there have been numerous
immunotherapeutic investigations in this patient population. A promising strategy
includes adoptive T cell therapy which has been studied in small cohorts of
synovial sarcoma, a subtype that is known to widely express the cancer testis
antigen, NY-ESO-1. Additionally, recent data in metastatic melanoma and renal
cell carcinoma demonstrate the utility and tremendous efficacy of immune
checkpoint blockade with increased rates of durable responses compared to
standard therapies. Responses in traditionally "non-immunogenic" tumors, such as
lung and bladder cancers, provide ample rationale for the study of immune
checkpoint inhibitors in sarcoma. While immunotherapy has induced some responses
in sarcomas, further research will help clarify optimal patient selection for
future clinical trials and new combinatorial immunotherapeutic strategies.
PMID- 26423772
TI - Incident diabetes mellitus, hypertension, and cardiovascular disease risk in
exercising hypercholesterolemic patients.
AB - Exercise may be an important treatment for hypercholesterolemic patients,
particularly in statin users who are at increased diabetes risk. We therefore
used Cox proportional hazard analyses to compare running and walking dose
(metabolic equivalent hours/day [MET-h/d]) to diabetes, hypertension, and
cardiovascular disease (CVD) risk in hypercholesterolemic patients. There were 60
diabetic- and 373 CVD-related deaths during a 10.1-year mortality surveillance of
6,688 hypercholesterolemic patients. In addition, there were 177 incident
nonfatal diabetes, 815 incident nonfatal hypertensions, and 323 incident nonfatal
CVD events during a 6.4-year follow-up of 6,971 hypercholesterolemic patients who
supplied follow-up questionnaires. Fatal and nonfatal diabetes risk decreased 26%
(p = 0.002) and 19% (p <=0.0001) per MET-h/d, respectively, and relative to <1.07
MET-h/d decreased 35% (p = 0.19) and 55% (p <=0.0001), respectively, for 1.8 to
3.6 MET-h/d and 73% (p = 0.02) and 71% (p <=0.0001), respectively, for >=3.6 MET
h/d. Fatal and nonfatal CVD risk decreased 8% (p = 0.008) and 3% (p = 0.22) per
MET-h/d, respectively, and relative to <1.07 MET-h/d decreased 10% (p = 0.45) and
36% (p = 0.008) for 1.8 to 3.6 MET-h/d, respectively, and 37% (p = 0.009) and 26%
(p = 0.10), respectively, for >=3.6 MET-h/d. Incident hypertension risk decreased
4% (p = 0.01) per MET-h/d, and relative to <1.07 MET-h/d decreased 29% (p =
0.002) for 1.8 to 3.6 MET-h/d and 31% (p = 0.001) for >=3.6 MET-h/d. In
conclusion, running and walking for exercise lowers diabetes, hypertension, and
CVD risk in hypercholesterolemic patients and should more than compensate for the
purported 9% increase in diabetes risk from statin use. By preventing morbidity
and mortality for a specific existing medical condition, some exercise expenses
may qualify for flexible spending account expenditures in hypercholesterolemic
patients when prescribed by a physician.
PMID- 26423773
TI - Juvenile exposure to vinclozolin shifts sex ratios and impairs reproductive
capacity of zebrafish.
AB - Exposure to endocrine disruptors during critical periods of development can
impact the sustainability of wild fish populations. Anti-androgenic compounds
have received less attention, but are capable of modulating gonad differentiation
and maturation, and impairing reproduction in fish. The fungicide vinclozolin
(VZ) has been shown to impair reproduction in adult fish, but less is known about
its effects following exposure earlier in development. Here we show that
waterborne exposure to 400MUg VZ/L during critical periods of sex differentiation
(21-35 days post fertilization) permanently shifts sex ratios towards females,
and alters the maturation of the gonad. Both fecundity and fertility were
reduced, even when oogenesis and spermatogenesis recover and sperm motility is
not altered. These results demonstrate the need to better understand the impacts
of early exposure to anti-androgenic compounds on fish.
PMID- 26423774
TI - Brain substrates of perceived spatial separation between speech sources under
simulated reverberant listening conditions in schizophrenia.
AB - BACKGROUND: People with schizophrenia recognize speech poorly under multiple
people-talking (informational masking) conditions. In reverberant environments,
direct-wave signals from a speech source are perceptually integrated with the
source reflections (the precedence effect), forming perceived spatial separation
(PSS) between different sources and consequently improving target-speech
recognition against informational masking. However, the brain substrates
underlying the schizophrenia-related vulnerability to informational masking and
whether schizophrenia affects the unmasking effect of PSS are largely unknown.
METHOD: Using psychoacoustic testing and functional magnetic resonance imaging,
respectively, the speech recognition under either the PSS or perceived spatial co
location (PSC) condition and the underlying brain substrates were examined in 20
patients with schizophrenia and 16 healthy controls. RESULTS: Speech recognition
was worse in patients than controls. Under the PSS (but not PSC) condition,
speech recognition was correlated with activation of the superior parietal lobule
(SPL), and target speech-induced activation of the SPL, precuneus, middle
cingulate cortex and caudate significantly declined in patients. Moreover, the
separation (PSS)-against-co-location (PSC) contrast revealed (1) activation of
the SPL, precuneus and anterior cingulate cortex in controls, (2) suppression of
the SPL and precuneus in patients, (3) activation of the pars triangularis of the
inferior frontal gyrus and middle frontal gyrus in both controls and patients,
(4) activation of the medial superior frontal gyrus in patients, and (5) impaired
functional connectivity of the SPL in patients. CONCLUSIONS: Introducing the PSS
listening condition efficiently reveals both the brain substrates underlying
schizophrenia-related speech-recognition deficits against informational masking
and the schizophrenia-related neural compensatory strategy for impaired SPL
functions.
PMID- 26423776
TI - [Ibn al Haizam and the International Year of Light].
PMID- 26423775
TI - A robust screening method for dietary agents that activate tumour-suppressor
microRNAs.
AB - Certain dietary agents, such as natural products, have been reported to show anti
cancer effects. However, the underlying mechanisms of these substances in human
cancer remain unclear. We recently found that resveratrol exerts an anti-cancer
effect by upregulating tumour-suppressor microRNAs (miRNAs). In the current
study, we aimed to identify new dietary products that have the ability to
activate tumour-suppressor miRNAs and that therefore may serve as novel tools for
the prevention and treatment of human cancers. We describe the generation and use
of an original screening system based on a luciferase-based reporter vector for
monitoring miR-200c tumour-suppressor activity. By screening a library containing
139 natural substances, three natural compounds - enoxolone, magnolol and
palmatine chloride - were identified as being capable of inducing miR-200c
expression in breast cancer cells at 10 MUM. Moreover, these molecules suppressed
the invasiveness of breast cancer cells in vitro. Next, we identified a molecular
pathway by which the increased expression of miR-200c induced by natural
substances led to ZEB1 inhibition and E-cadherin induction. These results
indicate that our method is a valuable tool for a fast identification of natural
molecules that exhibit tumour-suppressor activity in human cancer through miRNA
activation.
PMID- 26423777
TI - Patients with cirrhosis in the ED: early predictors of infection and mortality.
AB - BACKGROUND: Patients with cirrhosis have high risk of bacterial infections and
cirrhosis decompensation, resulting in admission to emergency department (ED).
However, there are no criteria developed in the ED to identify patients with
cirrhosis with bacterial infection and with high mortality risk. STUDY OBJECTIVE:
The objective of the study is to identify variables from ED arrival associated
with bacterial infections and inhospital mortality. METHODS: This is a
retrospective single-center study using a tertiary hospital's database to
identify consecutive ED patients with decompensated cirrhosis. Clinical variables
and laboratory results were obtained by chart review. Logistic regression models
were built to determine variables independently associated with bacterial
infection and mortality. Scores using these variables were designed. RESULTS: One
hundred forty-nine patients were enrolled, most of them males (77.9%) with
alcoholic cirrhosis (53%) and advanced liver disease (Child-Pugh C, 47.2%).
Bacterial infections were diagnosed in 72 patients (48.3%), and 36 (24.2%) died
during hospital stay. Variables independently associated with bacterial infection
were lymphocytes less than or equal to 900/mm(3) (odds ratio [OR], 3.85 [95%
confidence interval {CI}, 1.47-10]; P = .006) and C-reactive protein greater than
59.4 mg/L (OR, 5.05 [95% CI, 1.93-13.2]; P = .001). Variables independently
associated with mortality were creatinine greater than 1.5 mg/dL (OR, 4.35 [95%
CI, 1.87-10.1]; P = .001) and international normalized ratio greater than 1.65
(OR, 3.71 [95% CI, 1.6-8.61]; P = .002). Scores designed to predict bacterial
infection and mortality (Mortality in Cirrhosis Emergency Department Score) had
an area under the receiver operating characteristic curve of 0.82 and 0.801,
respectively. The Mortality in Cirrhosis Emergency Department Score performed
better than Model for End-Stage Liver Disease score. CONCLUSIONS: In this cohort
of ED patients with decompensated cirrhosis, lymphopenia and elevated C-reactive
protein were related to bacterial infections, and elevated creatinine and
international normalized ratio were related to mortality. Scores built with these
variables should be prospectively validated.
PMID- 26423779
TI - [Management of hepatitis B virus and hepatitis C virus infection in chronic
kidney failure].
AB - Chronic infections by hepatitis B (HBV) and C virus (HCV) result in diagnosis and
therapeutic issues in dialysis and kidney recipients patients. The exposure to
nosocomial, including blood transfusion, risk explains the high prevalence of HBV
and HCV infection in this setting. Chronic infection reduces the survival of both
patients and allografts, including a specific risk of de novo glomerulonephritis.
Cirrhosis was considered as a contra-indication to renal transplantation given
the high risk of decompensation and death, questionning the indication of a
combined liver and kidney transplantation. Thus, it is mandatory to screen HBV
and HCV markers in all dialysis patients, whether or not they are candidates to
transplantation. Liver biopsy allows evaluating the severity of the liver disease
since the noninvasive markers of fibrosis appear to be less accurate in "renal"
patients than in the general population and to better define antiviral
therapeutic indications. HCV treatment was mainly based on pegylated interferon
alpha (and low doses of ribavirin), which is contra-indicated in kidney
recipients given the risk of graft rejection; HCV treatment is now based on the
use of oral direct acting antivirals, which are very potent and well tolerated.
HBV replication is now easily suppressed by second-generation nucleos(t)tidic
analogues (entecavir and tenofovir), which will be indicated in all the dialysis
patients with significant fibrosis (F2,3 or 4 according to the Metavir scoring
system) and in any candidate to renal transplantation and to any HBsAg-positive
kidney recipients. The best treatment remains preventive by anti-HBV vaccination
for HBV and by the respect of universal hygiene rules for HCV.
PMID- 26423778
TI - A trend analysis of antimicrobial resistance in commensal Escherichia coli from
several livestock species in Belgium (2011-2014).
AB - A temporal trend analysis was performed on antimicrobial resistance data
collected over 4 consecutive years (2011-2014) in the official Belgian
antimicrobial resistance monitoring programme. Commensal Escherichia coli strains
were isolated from faecal samples of four livestock categories (veal calves,
young beef cattle, broiler chickens and slaughter pigs) and the trends of
resistance profiles were analysed. The resistance prevalence remained high (>50%)
during the study period for ampicillin in veal calves and chickens, for
ciprofloxacin and nalidixic acid in chickens, for sulfamethoxazole in veal
calves, chickens and pigs and for tetracycline in veal calves. Using logistic
regression and Generalized Estimating Equation and after p value adjustment for
multiple testing (Linear step-up method), statistically significant decreasing
temporal trends were observed for several of the 11 tested antimicrobials in
several livestock categories: in veal calves (10/11), in chickens (6/11) and in
pigs (5/11). A significant increasing trend was observed for the prevalence of
resistance to ciprofloxacin in chickens. Multi-resistance, considered as the
resistance to at least three antimicrobials of different antibiotic classes, was
observed in the four livestock categories but was significantly decreasing in
veal calves, chickens and pigs. Overall, the prevalence of resistance and of
multi-resistance was lowest in the beef cattle livestock category and highest in
broiler chickens. These decreasing temporal trends of antimicrobial resistance
might be due to a decrease of the total antimicrobial consumption for veterinary
use in Belgium which was reported for the period between 2010 and 2013. The
methodology and statistical tools developed in this study provide outputs which
can detect shifts in resistance levels or resistance trends associated with
particular antimicrobial classes and livestock categories. Such outputs can be
used as objective evidence to evaluate the possible efficacy of measures taken by
animal health authorities and stakeholders in the livestock sector to limit
antimicrobial resistance occurrence.
PMID- 26423780
TI - Influence of the Homopolar Dihydrogen Bonding C-H???H-C on Coordination Geometry:
Experimental and Theoretical Studies.
AB - The reaction of the N-thiophosphorylated thiourea (HOCH2 )(Me)2
CNHC(S)NHP(S)(OiPr)2 (HL), deprotonated by the thiophosphorylamide group, with
NiCl2 leads to green needles of the pseudotetrahedral complex [Ni(L-1,5-S,S')2
]?0.5 (n-C6 H14 ) or pale green blocks of the trans square-planar complex trans
[Ni(L-1,5-S,S')2 ]. The former complex is stabilized by homopolar dihydrogen C
H???H-C interactions formed by n-hexane solvent molecules with the [Ni(L-1,5
S,S')2 ] unit. Furthermore, the dispersion-dominated C-H??? H-C interactions are,
together with other noncovalent interactions (C-H???N, C-H???Ni, C-H???S),
responsible for pseudotetrahedral coordination around the Ni(II) center in [Ni(L
1,5-S,S')2 ]?0.5 (n-C6 H14 ).
PMID- 26423781
TI - First report on the bacterial diversity in the distal gut of dholes (Cuon
alpinus) by using 16S rRNA gene sequences analysis.
AB - The aim of this study was to investigate the bacterial community in the distal
gut of dholes (Cuon alpinus) based on the analysis of bacterial 16S rRNA gene
sequences. Fecal samples were collected from five healthy unrelated dholes
captured from Qilian Mountain in Gansu province of China. The diversity of the
fecal bacteria community was investigated by constructing a polymerase chain
reaction (PCR)-amplified 16S rRNA gene clone library. Bacterial 16S rRNA gene was
amplified by using universal bacterial primers 27F and 1492R. A total of 275
chimera-free near full length 16S rRNA gene sequences were collected, and 78 non
redundant bacteria phylotypes (operational taxonomical units, OTUs) were
identified according to the 97 % sequence similarity. Forty-two OTUs (53.8 %)
showed less than 98 % sequence similarity to 16S rRNA gene sequences reported
previously. Phylogenetic analysis demonstrated that dhole bacterial community
comprised five different phyla, with the majority of sequences being classified
within the phylum Bacteroidetes (64.7 %), followed by Firmicutes (29.8 %),
Fusobacteria (4.7 %),Proteobacteria (0.4 %), and Actinobacteria (0.4 %). The only
order Bacteroidales in phylum Bacteroidetes was the most abundant bacterial group
in the intestinal bacterial community of dholes. Firmicutes and Bacteroidetes
were the two most diverse bacterial phyla with 46.2 and 44.9 % of OTUs contained,
respectively. Bacteroidales and Clostridiales were the two most diverse bacterial
orders that contained 44.9 and 39.7 % of OTUs, respectively.
PMID- 26423782
TI - A lack of Wolbachia-specific DNA in samples from apollo butterfly (Parnassius
apollo, Lepidoptera: Papilionidae) individuals with deformed or reduced wings.
AB - Various insects contain maternally inherited endosymbiotic bacteria which can
cause reproductive alterations, modulation of some physiological responses (like
immunity, heat shock response, and oxidative stress response), and resistance to
viral infections. In butterflies, Wolbachia sp. is the most frequent endosymbiont
from this group, occurring in about 30 % of species tested to date. In this
report, the presence of Wolbachia-specific DNA has been detected in apollo
butterfly (Parnassius apollo). In the isolated population of this insect
occurring in Pieniny National Park (Poland), malformed individuals with deformed
or reduced wings appear with an exceptionally high frequency. Interestingly,
while total DNA isolated from most (about 85 %) normal insects contained
Wolbachia-specific sequences detected by PCR, such sequences were absent in a
large fraction (70 %) of individuals with deformed wings and in all tested
individuals with reduced wings. These results indicate for the first time the
correlation between malformation of wings and the absence of Wolbachia sp. in
insects. Although the lack of the endosymbiotic bacteria cannot be considered as
the sole cause of the deformation or reduction of wings, one might suggest that
Wolbachia sp. could play a protective role in the ontogenetic development of
apollo butterfly.
PMID- 26423783
TI - PCR method for the rapid detection and discrimination of Legionella spp. based on
the amplification of pcs, pmtA, and 16S rRNA genes.
AB - Legionella bacteria are organisms of public health interest due to their ability
to cause pneumonia (Legionnaires' disease) in susceptible humans and their
ubiquitous presence in water supply systems. Rapid diagnosis of Legionnaires'
disease allows the use of therapy specific for the disease. L. pneumophila
serogroup 1 is the most common cause of infection acquired in community and
hospital environments. The non-L. pneumophila infections are likely under
detected because of a lack of effective diagnosis. In this work, simplex and
duplex PCR assays with the use of new molecular markers pcs and pmtA involved in
phosphatidylcholine synthesis were specified for rapid and cost-efficient
identification and distinguishing Legionella species. The sets of primers
developed were found to be sensitive and specific for reliable detection of
Legionella belonging to the eight most clinically relevant species. Among these,
four primer sets I, II, VI, and VII used for duplex-PCRs proved to have the
highest identification power and reliability in the detection of the bacteria.
Application of this PCR-based method should improve detection of Legionella spp.
in both clinical and environmental settings and facilitate molecular typing of
these organisms.
PMID- 26423784
TI - Intrapleural Fibrinolysis with Urokinase Versus Alteplase in Complicated
Parapneumonic Pleural Effusions and Empyemas: A Prospective Randomized Study.
AB - BACKGROUND: Pleurofibrinolysis has been reported to be potentially beneficial in
the management of complicated parapneumonic effusions (CPPE) and empyemas in the
adult population. METHODS: Prospective, controlled, randomized, and double-blind
study, to evaluate intrapleural alteplase 10 mg (initially 20 mg was considered
but bleeding events forced dose reduction) versus 100,000 UI urokinase every 24 h
for a maximum of 6 days in patients with CPPE or empyemas. The primary aim was to
evaluate the success rate of each fibrinolytic agent at 3 and 6 days. Success of
therapy was defined as the presence of both clinical and radiological
improvement, making additional fibrinolytic doses unnecessary, and eventually
leading to resolution. Secondary outcomes included the safety profile of
intrapleural fibrinolytics, referral for surgery, length of hospital stay, and
mortality. RESULTS: A total of 99 patients were included, of whom 51 received
alteplase and 48 urokinase. Success rates for urokinase and alteplase at 3 and 6
days were not significantly different, but when only the subgroup of CPPE was
considered, urokinase resulted in a high proportion of cures. There were no
differences in mortality or surgical need (overall, 3 %). Five (28 %) patients
receiving 20 mg of alteplase and 4 (12 %) receiving 10 mg presented serious
bleeding events. CONCLUSIONS: If intrapleural fibrinolytics are intended to be
used, urokinase may be more effective than alteplase in patients with non
purulent CPPE and have a lower rate of adverse events.
PMID- 26423785
TI - Maternal high fat diet programs stress-induced behavioral disorder in adult
offspring.
AB - Early life exposure to specific environmental factors can contribute to
development of behavioral disorders in adulthood. Although maternal high fat diet
(HFD) consumption during the perinatal period has been reported to program
offspring behavior, the underlying mechanisms remain to be elucidated. The
present study was designed to evaluate the influence of maternal HFD on offspring
behavior under nonstressed and stressful conditions, using male Sprague-Dawley
offspring, which mothers were fed with HFD or normal diet (ND), receiving chronic
unpredictable mild stress (CUMS) in the adulthood. We found that although the
detrimental effects of maternal HFD consumption on offspring depressive behavior
did not persist into adulthood, it markedly aggravated the behavioral disorder
response to stressful challenge in adult offspring. Moreover, calcitonin gene
related peptide (CGRP) concentration in CSF and hippocampus were increased in the
HFD+CUMS rats, compared to the ND+CUMS subjects. Another separate groups were
fitted with intracerebroventricular (icv) cannulae. Central infusion of
alphaCGRP8-37, a CGRP antagonist, produced antidepressant effects in HFD+CUMS
rats, implying that the programming of maternal HFD on offspring behavior
responses to stress may be mediated partially by endogenous central CGRP
signaling. Moreover, we found that maternal HFD significantly exacerbated HPA
profile response to acute restraint stress and attenuated the habituation of HPA
responses to repeated restraint stress, suggesting that maternal HFD may program
the changes of HPA-regulatory mechanisms. Overall, our findings suggest that
maternal HFD influence adult depressive disorder response to stressful challenge,
through the modulation of endogenous central CGRP signaling and HPA-regulatory
components.
PMID- 26423786
TI - Effects of environmental stress following myocardial infarction on behavioral
measures and heart failure progression: The influence of isolated and group
housing conditions.
AB - BACKGROUND: Heart failure (HF) prognosis is negatively influenced by adverse
environmental conditions associated with psychological distress and depression.
The underlying mechanisms are not well understood because of insufficient
experimental control in prior clinical and epidemiological studies. Using a
validated animal model we examined whether distress-producing environmental
manipulations (social isolation and crowding) increase HF progression following
myocardial infarction (MI). METHODS: MI was induced using coronary artery
ligation in 8-week old male Wistar rats (N=52) and results were compared to sham
surgery (N=24). Housing conditions were randomly assigned at 5 days post MI or
sham surgery (1/cage=isolation, 2/cage=standard reference condition, or
4/cage=crowding) and continued for 17 weeks until the end of observation. The
open field test was used to test behavioral responses. Echocardiograms were
obtained at weeks 8 and 16, and left ventricular (LV) weight at week 17. RESULTS:
Housing conditions increased behavioral markers of distress (p=0.046) with the
strongest effects for the isolated (1/cage) (p=0.022). MI did not increase
distress-related behaviors compared to sham. MI-surgery resulted in
characteristic HF indices (left ventricular ejection fraction (LVEF) at week
16=46 +/- 12% vs. 80 +/- 7% in sham, p<0.001). Housing condition was not related
to LVEF or LV weight (p>0.10). CONCLUSIONS: Adverse environmental conditions,
particularly isolated housing, produce increases in some of the behavioral
indicators of distress. No effects of housing were found on post-MI progression
of HF. The distress-HF associations observed in humans may therefore reflect
common underlying factors rather than an independent causal pathway. Stronger
environmental challenges may be needed in future animal research examining
distress as related HF progression.
PMID- 26423788
TI - Metabolic approaches to antihypertensive treatment in diabetic patients.
PMID- 26423787
TI - Pre-existing differences in motivation for food and sensitivity to cocaine
induced locomotion in obesity-prone rats.
AB - Obesity is a significant problem in the United States, with roughly one third of
adults having a body mass index (BMI) over thirty. Recent evidence from human
studies suggests that pre-existing differences in the function of mesolimbic
circuits that mediate motivational processes may promote obesity and hamper
weight loss. However, few preclinical studies have examined pre-existing
neurobehavioral differences related to the function of mesolimbic systems in
models of individual susceptibility to obesity. Here, we used selectively bred
obesity-prone and obesity-resistant rats to examine 1) the effect of a novel
"junk-food" diet on the development of obesity and metabolic dysfunction, 2) over
consumption of "junk-food" in a free access procedure, 3) motivation for food
using instrumental procedures, and 4) cocaine-induced locomotor activity as an
index of general mesolimbic function. As expected, eating a sugary, fatty, "junk
food" diet exacerbated weight gain and increased fasted insulin levels only in
obesity-prone rats. In addition, obesity-prone rats continued to over-consume
junk-food during discrete access testing, even when this same food was freely
available in the home cage. Furthermore, when asked to press a lever to obtain
food in an instrumental task, rates of responding were enhanced in obesity-prone
versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger
locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior
to any diet manipulation. This enhanced sensitivity to this dose of cocaine is
indicative of basal differences in the function of mesolimbic circuits in obesity
prone rats. We speculate that pre-existing differences in motivational systems
may contribute to over-consumption and enhanced motivation in susceptible
individuals.
PMID- 26423789
TI - Multifunctional L/N- and L/T-type calcium channel blockers for kidney protection.
PMID- 26423790
TI - A Defence of the Counterfactual Account of Harm.
AB - In order to determine whether a particular course of conduct is ethically
permissible it is important to have a concept of what it means to be harmed. The
dominant theory of harm is the counterfactual account, most famously proposed by
Joel Feinberg. This determines whether harm is caused by comparing what actually
happened in a given situation with the 'counterfacts' i.e. what would have
occurred had the putatively harmful conduct not taken place. If a person's
interests are worse off than they otherwise would have been, then a person will
be harmed. This definition has recently faced challenges from bioethicists such
as John Harris, Guy Kahane and Julian Savulescu who, believing it to be severely
flawed, have proposed their own alternative theories of the concept. In this
article I will demonstrate that the shortcomings Harris, Kahane and Savulescu
believe are present in Feinberg's theory are illusory and that it is their own
accounts of harm that are fraught with logical errors. I maintain that the
arguments presented to refute Feinberg's theory not only fail to achieve this
goal and can be accommodated within the counterfactual account but that they
actually undermine the theories presented by their respective authors. The final
conclusion will be that these challenges are misconceived and fail to displace
the counterfactual theory.
PMID- 26423791
TI - Getting past the dual logic: findings from a pilot asset mapping exercise in
Sheffield, UK.
AB - Asset-based approaches seek to identify and mobilise the personal, social and
organisational resources available to communities. Asset mapping is a recognised
method of gathering an inventory of neighbourhood assets and is underpinned by a
fundamentally different logic to traditional needs assessments. The aim of this
paper is to explore how asset mapping might be used as a tool for health
improvement. It reports on a qualitative evaluation of a pilot asset mapping
project carried out in two economically disadvantaged neighbourhoods in
Sheffield, UK. The project involved community health champions working with two
community organisations to identify assets linked to the health and wellbeing of
their neighbourhoods. The evaluation was undertaken in 2012 after mapping
activities had been completed. A qualitative design, using theory of change
methodology, was used to explore assumptions between activities, mechanisms and
outcomes. Semi structured interviews were undertaken with a purposive sample of
11 stakeholders including champions, community staff and strategic partners.
Thematic analysis was used and themes were identified on the process of asset
mapping, the role of champions and the early outcomes for neighbourhoods and
services. Findings showed that asset mapping was developmental and understandings
grew as participatory activities were planned and implemented. The role of the
champions was limited by numbers involved, nonetheless meaningful engagement
occurred with residents which led to personal and social resources being
identified. Most early outcomes were focused on the lead community organisations.
There was less evidence of results feeding into wider planning processes because
of the requirements for more quantifiable information. The paper discusses the
importance of relational aspects of asset mapping both within communities and
between communities and services. The conclusions are that it is insufficient to
switch from the logic of needs to assets without building asset mapping as part
of a broader planning process.
PMID- 26423792
TI - Yeast Bud27 modulates the biogenesis of Rpc128 and Rpc160 subunits and the
assembly of RNA polymerase III.
AB - Yeast Bud27, an unconventional prefoldin is reported to affect the expression of
nutrient-responsive genes, translation initiation and assembly of the multi
subunit eukaryotic RNA polymerases (pols), at a late step. We found that Bud27
associates with pol III in active as well as repressed states. Pol III
transcription and occupancy at the target genes reduce with the deletion of
BUD27. It promotes the interaction of pol III with the chromatin remodeler RSC
found on most of the pol III targets, and with the heat shock protein Ssa4, which
helps in nuclear import of the assembled pol III. Under nutrient-starvation, Ssa4
pol III interaction increases, while pol III remains inside the nucleus. Bud27
but not Ssa4 is required for RSC-pol III interaction, which reduces under
nutrient-starvation. In the bud27Delta cells, total protein level of the largest
pol III subunit Rpc160 but not of Rpc128, Rpc34 and Rpc53 subunits is reduced.
This is accompanied by lower transcription of RPC128 gene and lower RPC160
translation due to reduced association of mRNA with the ribosomes. The resultant
alteration in the normal cellular ratio of the two largest subunits of pol III
core leads to reduced association of other pol III subunits and hampers the
normal assembly of pol III at an early step in the cytoplasm. Our results show
that Bud27 is required in multiple activities responsible for pol III biogenesis
and activity.
PMID- 26423793
TI - Tinea Incognito.
PMID- 26423794
TI - Examining the locations of medical marijuana dispensaries in Los Angeles.
AB - INTRODUCTION AND AIMS: Little is known about the spatial distribution of medical
marijuana dispensaries, particularly whether or not sites are disproportionately
located in minority or communities with younger populations. This paper will
assess if there is a relationship between medical marijuana dispensaries and
neighbourhood characteristics. DESIGN AND METHODS: This study used an ecological,
cross-sectional design of 1000 census tracts from Los Angeles city in 2012 to
explore the relationship between neighbourhood sociodemographics, structural
features of neighbourhoods and density of medical marijuana dispensaries.
Locations of dispensaries were obtained through a premise survey of all listed
dispensaries. Data on neighbourhood characteristics were obtained from Geolytics.
The study used Bayesian conditionally autoregressive models that include controls
for spatial heterogeneity to analyse the data. RESULTS: Findings show that
dispensaries are located in areas that allow for commercial establishments.
Results indicate a positive relationship between dispensaries and percent
commercially zoned, areas with highway ramp access, density of on- and off
premise alcohol outlets and percent Hispanic residents. DISCUSSION AND
CONCLUSIONS: In sum, the findings suggest that, likely because of zoning
regulations, dispensaries were located in primarily commercially zoned areas with
greater road access (as measured by the presence of highway ramps). Given that
areas with higher densities of dispensaries also have higher densities of alcohol
outlets, future work should examine how this co-location affects neighbourhood
problems such as crime and violence. [Thomas C, Freisthler B. Examining the
locations of medical marijuana dispensaries in Los Angeles. Drug Alcohol Rev
2016;35:334-337].
PMID- 26423795
TI - Phase I Study of the Investigational NEDD8-Activating Enzyme Inhibitor
Pevonedistat (TAK-924/MLN4924) in Patients with Advanced Solid Tumors.
AB - PURPOSE: To determine the dose-limiting toxicities (DLTs) and maximum tolerated
dose (MTD) of the investigational NEDD8-activating enzyme (NAE) inhibitor
pevonedistat (TAK-924/MLN4924) and to investigate pevonedistat pharmacokinetics
and pharmacodynamics in patients with advanced nonhematologic malignancies.
EXPERIMENTAL DESIGN: Pevonedistat was administered via 60-minute intravenous
infusion on days 1 to 5 (schedule A, n = 12), or days 1, 3, and 5 (schedules B, n
= 17, and C, n = 19) of 21-day cycles. Schedule B included oral dexamethasone 8
mg before each pevonedistat dose. Dose escalation proceeded using a Bayesian
continual reassessment method. Tumor response was assessed by RECIST 1.0.
RESULTS: Schedule A MTD was 50 mg/m(2); based on the severity of observed
hepatotoxicity, this schedule was discontinued. Schedules B and C MTDs were 50
and 67 mg/m(2), respectively. DLTs on both these schedules included
hyperbilirubinemia and elevated aspartate aminotransferase. There were no grade
>= 3 treatment-related serious adverse events reported on schedules B or C.
Twenty-three (74%) evaluable patients on schedules B and C had stable disease.
Intermittent dexamethasone use did not significantly influence pevonedistat
pharmacokinetics. NAE inhibition by pevonedistat was demonstrated in multiple
tumor types via IHC detection of pevonedistat-NEDD8 adduct and accumulation of
Cullin-RING ligase substrates CDT1 and NRF2 in tumor biopsies. CONCLUSIONS:
Pevonedistat was generally well tolerated on a day 1, 3, 5 schedule every 3 weeks
with an MTD between 50 mg/m(2) and 67 mg/m(2). DLTs were predominantly hepatic
enzyme elevations. Pharmacodynamic studies demonstrated that pevonedistat
inhibited NAE in tumors.
PMID- 26423796
TI - The IL-15-Based ALT-803 Complex Enhances FcgammaRIIIa-Triggered NK Cell Responses
and In Vivo Clearance of B Cell Lymphomas.
AB - PURPOSE: Anti-CD20 monoclonal antibodies (mAb) are an important immunotherapy for
B-cell lymphoma, and provide evidence that the immune system may be harnessed as
an effective lymphoma treatment approach. ALT-803 is a superagonist IL-15 mutant
and IL-15Ralpha-Fc fusion complex that activates the IL-15 receptor
constitutively expressed on natural killer (NK) cells. We hypothesized that ALT
803 would enhance anti-CD20 mAb-directed NK-cell responses and antibody-dependent
cellular cytotoxicity (ADCC). EXPERIMENTAL DESIGN: We tested this hypothesis by
adding ALT-803 immunostimulation to anti-CD20 mAb triggering of NK cells in vitro
and in vivo. Cell lines and primary human lymphoma cells were utilized as targets
for primary human NK cells. Two complementary in vivo mouse models were used,
which included human NK-cell xenografts in NOD/SCID-gammac (-/-) mice. RESULTS:
We demonstrate that short-term ALT-803 stimulation significantly increased
degranulation, IFNgamma production, and ADCC by human NK cells against B-cell
lymphoma cell lines or primary follicular lymphoma cells. ALT-803 augmented
cytotoxicity and the expression of granzyme B and perforin, providing one
potential mechanism for this enhanced functionality. Moreover, in two distinct in
vivo B-cell lymphoma models, the addition of ALT-803 to anti-CD20 mAb therapy
resulted in significantly reduced tumor cell burden and increased survival. Long
term ALT-803 stimulation of human NK cells induced proliferation and NK-cell
subset changes with preserved ADCC. CONCLUSIONS: ALT-803 represents a novel
immunostimulatory drug that enhances NK-cell antilymphoma responses in vitro and
in vivo, thereby supporting the clinical investigation of ALT-803 plus anti-CD20
mAbs in patients with indolent B-cell lymphoma.
PMID- 26423797
TI - Subtype-Specific Metagene-Based Prediction of Outcome after Neoadjuvant and
Adjuvant Treatment in Breast Cancer.
AB - PURPOSE: In spite of improvements of average benefit from adjuvant/neoadjuvant
treatments, there are still individual patients with early breast cancer at high
risk of relapse. We explored the association with outcome of robust gene cluster
based metagenes linked to proliferation, ER-related genes, and immune response to
identify those high-risk patients. EXPERIMENTAL DESIGN: A total of 3,847 publicly
available gene-expression profiles were analyzed (untreated, N = 826; tamoxifen
treated, N = 685; chemotherapy-treated, N = 1,150). Genes poorly performing in
formalin-fixed samples were removed. Outcomes of interest were pathologic
complete response (pCR) and distant metastasis-free survival (DMFS). In
ER(+)HER2(-), the proliferation and ER-related metagenes were combined to define
three risk groups. In HER2(+) and ER(-)HER2(-) risk groups were defined by
tertiles of an immune-related metagene. RESULTS: The high-proliferation/low-ER
group of ER(+)HER2(-) breast cancer had significantly higher pCR rate [OR, 5.01
(1.76-17.99), P = 0.005], but poorer outcome [HR = 3.73 (1.63-8.51), P = 0.0018]
than the low-proliferation/high-ER. A similar association with outcome applied to
patients with residual disease (RD) after neoadjuvant chemotherapy (P = 0.01). In
ER(-)HER2(-) and HER2(+) breast cancer, immune metagene in the high tertile was
linked to higher pCR [33.7% vs. 11.6% in high and low tertile, respectively; OR,
3.87 (1.79-8.95); P = 0.0009]. In ER(-)HER2(-), after adjuvant/neoadjuvant
chemotherapy, 5-year DMFS was 85.4% for high-tertile immune metagene, and 43.9%
for low tertile. The outcome association was similar in patients with RD (P =
0.0055). In HER2(+) breast cancer treated with chemotherapy the association with
risk of relapse was not significant. CONCLUSIONS: We developed metagene-based
predictors able to define low and high risk of relapse after adjuvant/neoadjuvant
therapy. High-risk patients so defined should be preferably considered for trials
with investigational agents.
PMID- 26423799
TI - Comparative metabolic study between two selective estrogen receptor modulators,
toremifene and tamoxifen, in human liver microsomes.
AB - Toremifene (TOR) and Tamoxifen (TAM) are widely used as endocrine therapy for
estrogen receptor positive breast cancer. Poor metabolizers of TAM are likely to
have worse clinical outcomes than patients who exhibit normal TAM metabolism due
to lower plasma level of its active metabolite, 4-hydroxy-N-desmethyl (4OH-NDM)
tamoxifen (endoxifen). In this study, we examined the role of individual
cytochrome P450 (CYP) isoforms in the metabolism of TOR to N-desmethyl (NDM), 4
hydroxy (4OH) and 4OH-NDM metabolites in comparison with TAM using human liver
microsomes (HLMs) with selective chemical inhibitors for each CYP isoform and
recombinant CYP proteins. Similar levels of NDM metabolites were formed for both
TOR and TAM, and N-demethylation of both compounds was primarily carried out by
CYP3A4. We found that the formation of 4OH-NDM-TOR was catalyzed both by CYP2C9
and CYP2D6, whereas the formation of 4OH-TAM and endoxifen was specifically
catalyzed by CYP2D6 in HLMs. Our results suggest that the potential contribution
of CYP2D6 in the bioactivation pathway of TOR may be lower compared to TAM, and
may have a different impact on clinical outcome than CYP2D6 polymorphisms.
PMID- 26423800
TI - Allelic polymorphism of KIR2DL2/2DL3 in a southern Chinese population.
AB - KIR2DL2 and KIR2DL3 segregate as alleles of the same killer cell immunoglobulin
like receptor (KIR) gene locus. They have been associated with viral infectious
diseases and certain cancers and their allelic information may help to better
comprehend mechanisms. The allelic polymorphism of KIR2DL2/2DL3 has been shown to
influence their binding specificity and affinity to the HLA-C1 ligands. The
present study aims to investigate the distribution of the allelic polymorphism of
KIR2DL2/2DL3 in a southern Chinese population using sequence-specific primer
polymerase chain reaction (PCR-SSP) and PCR-sequence-based typing (SBT) at the
entire coding sequence. Of the 306 tested individuals, 1.96% were positive for
KIR2DL2 only, 78.10% for KIR2DL3 only, and 19.93% for both KIR2DL2 and 2DL3.
KIR2DL3 showed a high degree of diversity in the study population with 15 alleles
detected including 8 novel ones. The predominant 2DL3 allele in the study
population is 2DL3*00101 (92.81%) followed by 2DL3*00201 (24.18%), 2DL3*023
(4.25%), and 2DL3*00109 (1.31%). The remaining 11 2DL3 alleles all had a
frequency below 1%. Three detected 2DL2 alleles were 2DL2*00301 (18.95%),
2DL2*00101 (3.59%), and the novel 2DL2*013 (0.33%). These results provide further
insight into the KIR gene diversity in Southern Chinese and may help to better
understand the role played by KIR genes in associated diseases.
PMID- 26423798
TI - A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a
highly susceptible strain of mice, from a Chlamydia muridarum genital challenge.
AB - C3H/HeN female mice were vaccinated with native Chlamydia muridarum major outer
membrane protein (MOMP), using Montanide+CpG or Alum+CpG as adjuvants. Negative
control groups were immunized with ovalbumin (OVA) and the same adjuvants. As
positive control, mice were inoculated intranasally with live Chlamydia. Mice
were challenged in the ovarian bursa with 10(5) C. muridarum inclusion forming
units. Six weeks after the genital challenge the animals were caged with male
mice and monitored for pregnancy. Mice vaccinated with MOMP+Montanide+CpG
developed high levels of C. muridarum-specific antibodies, with a high IgG2a/IgG1
ratio and neutralizing titres. Animals immunized using Alum+CpG had low antibody
levels. Cellular immune responses were significantly higher in mice vaccinated
with MOMP and Montanide+CpG, but not with Alum+CpG, when compared with negative
controls. Following the genital challenge, only 20% (4/20) of mice vaccinated
with MOMP+CpG+Montanide had positive vaginal cultures whereas 100% (9/9) of mice
immunized with MOMP+CpG+Alum had positive cultures. Of the positive control
animals inoculated with live Chlamydia only 15% (3/20) had positive vaginal
cultures. In contrast, 100% (20/20) of mice immunized with OVA+CpG+Montanide, or
minimal essential medium, had positive cultures. Following mating, 80% (16/20) of
mice vaccinated with MOMP+CpG+Montanide, and 85% (17/20) of animals inoculated
intranasally with live C. muridarum carried embryos in both uterine horns. No
protection against infertility was observed in mice immunized with MOMP and
CpG+Alum or OVA. In conclusion, this is the first time that a subunit vaccine has
been shown to elicit a protective immune response in the highly susceptible
C3H/HeN strain of mice against an upper genital challenge.
PMID- 26423802
TI - Endoplasmic reticulum stress and autophagy participate in apoptosis induced by
bortezomib in cervical cancer cells.
AB - OBJECTIVES: To determine the role of endoplasmic reticulum (ER) stress and
autophagy in apoptosis induced by bortezomib in human cervical cancer-derived
HeLa cells and CaSki cells. RESULTS: Bortezomib treatment activated apoptosis,
evidenced by increased expression of cleaved caspase-3 and cleaved PARP in both
HeLa cells and CaSki cells. Bortezomib also induced the loss of the mitochondrial
membrane potential, increased the level of ER stress-associated proteins GRP78,
ATF4, and CCAAT-enhancer-binding protein homologous protein, and affected the
expression of autophagy-related proteins; increasing the levels of LC3-II and
ATG5-ATG12 and decreasing the level of p62. When we combined bortezomib with the
ER stress activator tunicamycin, or autophagy inhibitors 3-methyladenine or
chloroquine, cell growth inhibition and apoptosis were markedly enhanced.
CONCLUSIONS: Bortezomib activates apoptosis signaling, and activation of ER
stress and inhibition of autophagy enhances the cytotoxicity of bortezomib,
suggesting that these combination treatments may be potential chemotherapy
strategies for treating cervical cancer.
PMID- 26423801
TI - Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy)
irradiation plus concomitant temozolomide in elderly patients with glioblastoma:
a multicenter retrospective study of AINO (Italian Association of Neuro
Oncology).
AB - The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly
patients with glioblastoma is unclear. We performed a large multicenter
retrospective study to analyze prognostic factors and clinical outcome in these
patients. Inclusion criteria were age >=65 years, newly histologically confirmed
glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237
patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total
resection was performed in 174 cases. MGMT was analyzed in 151 persons and was
methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %.
Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy.
Progression-free survival and overall survival (OS) were 11.3 and 17.3 months,
respectively. Overall survival was 19.4 vs 13.8 months for patients treated with
RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients
treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2
versus 13.6 months for methylated and unmethylated MGMT (p < 0.001). On
multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG
PS 0-1 were independent predictors of longer survival. Twenty-five patients (10
%) had grade 3-4 haematological toxicity during the concomitant treatment. We
showed that, in elderly patients in good clinical condition treated with
concomitant treatment, standard-course irradiation might be more effective than
short-course irradiation. Methylated MGMT remains the most important prognostic
factor.
PMID- 26423803
TI - Epidermal growth factor receptor inhibition with erlotinib ameliorates anti-Thy
1.1-induced experimental glomerulonephritis.
AB - BACKGROUND: Mesangial proliferative glomerulonephritis is a common glomerular
disorder that may lead to end-stage renal disease. Epidermal growth factor (EGF)
plays an important role in the regulation of cell growth, proliferation, and
differentiation and in the pathology of various renal diseases. Erlotinib is a
novel, oral, highly selective tyrosine kinase inhibitor of the EGF receptor. It
is clinically used to treat non-small cell lung and pancreatic cancers. Here, we
investigated the effect of erlotinib on the progression of mesangioproliferative
glomerulonephritis in an experimental model. METHODS: Mesangial
glomerulonephritis was induced with anti-rat Thy-1.1 antibody in male Wistar rats
weighing 150-160 g. Rats were treated with erlotinib (10 mg/kg/day p.o.) or
vehicle only (polyethylene glycol). Native Wistar rat kidneys were used as
histological controls. Serum creatinine levels were measured at day 7. Kidneys
were harvested 7 days after antibody administration for histology. RESULTS:
Native controls showed no histological signs of glomerular pathology. In the
vehicle group, intense glomerular inflammation developed after 7 days and
prominent mesangial cell proliferation and glomerular matrix accumulation was
seen. Erlotinib was well tolerated and there were no adverse effects during the
follow-up period. Erlotinib significantly prevented progression of the glomerular
inflammatory response and glomerular mesangial cell proliferation as well as
matrix accumulation when compared with the vehicle group. Erlotinib also
preserved renal function. CONCLUSION: These results indicate that erlotinib
prevents the early events of experimental mesangial proliferative
glomerulonephritis. Therefore, inhibition of the EGF receptor with erlotinib
could prevent the progression of glomerulonephritis also in clinical nephrology.
PMID- 26423804
TI - Cattell-Braasch Maneuver Combined with Artery-First Approach for Superior
Mesenteric-Portal Vein Resection During Pancreatectomy.
AB - Pancreatectomy associated with superior mesenteric-portal vein (SMPV) resection
is currently considered the standard of care for patients with pancreatic tumors
involving the major peripancreatic veins. However, a standard approach for
resection and reconstruction is not defined yet. The aim of this study is to
analyze the feasibility and short-term results of an original Cattell-Braasch
artery-first approach (CBAF) for the resection of SMPV during pancreatectomy. Of
144 pancreatectomies with vascular resection undertaken from 2008 to 2013 at
Karolinska University Hospital, 45 (31.2 %) were performed combining a Cattell
Braasch maneuver with an artery-first approach (from 2011 to 2013). The mean
patient age was 65.2 years. Thirty-seven (82.2 %) patients underwent
pancreatoduodenectomy and 8 (17.8 %) total pancreatectomy. Histology showed
pancreatic ductal adenocarcinoma in 42 patients (93.3 %). The median length of
the resected SMPV segment was 4.6 cm (range 3-7). In all patients, a direct end
to-end anastomosis was performed without graft interposition. In nine cases (20
%), an arterial resection was also performed. There was no mortality in this
series, and the morbidity rate was 35.5 %. Combined CBAF for the resection of
SMPV during pancreatectomy seems to be safe and effective. The reconstruction of
the resected vessels is possible in many cases without graft interposition, even
if the resected vein segment is of considerable length.
PMID- 26423805
TI - Effect of rituximab on adult Burkitt's lymphoma: a systematic review and meta
analysis.
AB - The treatment of Burkitt's lymphoma with rituximab is controversial, and studies
that compared the efficacy of chemotherapy alone with chemotherapy plus rituximab
have not been powered to test differences in overall survival (OS). We conducted
this systematic review and meta-analysis to identify the value of rituximab for
the treatment of BL to guide treatment decisions. Based on the PubMed, Web of
Science, and Cochrane library online electronic databases, all retrospective and
randomized clinical trial studies that compared the aforementioned two regimens
were included. The pooled hazard ratio and odds ratio were analyzed using Review
Manager 5.3. The primary outcome was the 2-year OS. A total of 581 publications
were identified using a predetermined search strategy. One randomized controlled
trial (RCT) and five retrospective studies, which included 646 cases (351 cases
for the chemotherapy with rituximab group and 295 cases for the chemotherapy
alone group), fulfilled the selection criteria and were included in the meta
analysis. The chemotherapy with rituximab group was associated with a higher 2
year OS (hazard ratio 0.62, 95 % CI 0.45-0.85, P = 0.003), 2-year progression
free survival (hazard ratio 0.46, 95 % CI 0.43-0.50, P < 0. 001), and complete
remission rate (odds ratios 3.26, 95 % CI 1.22-8.66, P = 0.02). In addition, the
treatment-related mortality did not significantly differ between the two
treatment regimens (odds ratio 1.16, 95 % CI 0.55-2.45, P = 0.69). The meta
analysis indicates that the addition of rituximab to the treatment regimen for
Burkitt's lymphoma may be associated with a significant survival benefit and did
not increase the mortality compared with chemotherapy alone.
PMID- 26423807
TI - Postnatal depressive symptoms amongst women in Central Vietnam: a cross-sectional
study investigating prevalence and associations with social, cultural and infant
factors.
AB - BACKGROUND: This study investigated the prevalence and socio-cultural correlates
of postnatal mood disturbance amongst women 18-45 years old in Central Vietnam.
Son preference and traditional confinement practices were explored as well as
factors such as poverty, parity, family and intimate partner relationships and
infant health. METHODS: A cross-sectional study was conducted in twelve randomly
selected Commune Health Centres from urban and rural districts of Thua Thien Hue
Province, Vietnam. Mother-infant dyads one to six months postpartum were invited
to participate. Questionnaires from 431 mothers (urban n = 216; rural n = 215)
assessed demographic and family characteristics, traditional confinement
practices, son preference, infant health and social capital. The Edinburgh
Postnatal Depression Scale (EPDS) and WHO5 Wellbeing Index indicated depressive
symptoms and emotional wellbeing. Data were analysed using general linear models.
RESULTS: Using an EPDS cut-off of 12/13, 18.1% (n = 78, 95% CI 14.6-22.1) of
women had depressive symptoms (20.4% urban; 15.8% rural). Contrary to
predictions, infant gender and traditional confinement were unrelated to
depressive symptoms. Poverty, food insecurity, being frightened of family
members, and intimate partner violence increased both depressive symptoms and
lowered wellbeing. The first model accounted for 30.2% of the variance in EPDS
score and found being frightened of one's husband, husband's unemployment,
breastfeeding difficulties, infant diarrhoea, and cognitive social capital were
associated with higher EPDS scores. The second model had accounted for 22% of the
variance in WHO5 score. Living in Hue city, low education, poor maternal
competence and a negative family response to the baby lowered maternal wellbeing.
CONCLUSIONS: Traditional confinement practices and son preference were not linked
to depressive symptoms among mothers, but were correlates of family relationships
and wellbeing. Poverty, food insecurity, violence, infant ill health, and
discordant intimate and family relationships were linked with depressive symptoms
in Central Vietnam.
PMID- 26423809
TI - The Lancet HIV: a journal for a new era of AIDS.
PMID- 26423806
TI - White matter deficits assessed by diffusion tensor imaging and cognitive
dysfunction in psychostimulant users with comorbid human immunodeficiency virus
infection.
AB - BACKGROUND: Psychostimulant drug use is commonly associated with drug-related
infection, including the human immunodeficiency virus (HIV). Both psychostimulant
use and HIV infection are known to damage brain white matter and impair
cognition. To date, no study has examined white matter integrity using magnetic
resonance imaging (MRI) diffusion tensor imaging (DTI) in chronic psychostimulant
users with comorbid HIV infection, and determined the relationship of white
matter integrity to cognitive function. METHODS: Twenty-one subjects (mean age
37.5 +/- 9.0 years) with a history of heavy psychostimulant use and HIV infection
(8.7 +/- 4.3 years) and 22 matched controls were scanned on a 3T MRI. Fractional
anisotropy (FA) values were calculated with DTI software. Four regions of
interest were manually segmented, including the genu of the corpus callosum, left
and right anterior limbs of the internal capsule, and the anterior commissure.
Subjects also completed a neurocognitive battery and questionnaires about
physical and mental health. RESULTS: The psychostimulant using, HIV positive
group displayed decreased white matter integrity, with significantly lower FA
values for all white matter tracts (p < 0.05). This group also exhibited
decreased cognitive performance on tasks that assessed cognitive set-shifting,
fine motor speed and verbal memory. FA values for the white matter tracts
correlated with cognitive performance on many of the neurocognitive tests.
CONCLUSIONS: White matter integrity was thus impaired in subjects with
psychostimulant use and comorbid HIV infection, which predicted worsened
cognitive performance on a range of tests. Further study on this medical
comorbidity is required.
PMID- 26423808
TI - Methicillin-resistant Staphylococcus pseudintermedius (MRSP) from healthy dogs in
Norway - occurrence, genotypes and comparison to clinical MRSP.
AB - The aim of the study was to investigate the occurrence of methicillin-resistant
Staphylococcus pseudintermedius (MRSP) in healthy dogs and further to determine
genetic relatedness between carrier isolates and clinical MRSP from dogs in
Norway. A total of 189 healthy dogs visiting ten veterinary clinics were screened
for MRSP during the period February to April 2013. Carrier isolates were
susceptibility tested with disk diffusion and genotyped using multilocus sequence
typing (MLST) and pulsed-field gel electrophoresis (PFGE). Forty-nine clinical
MRSP were characterized for comparison. These isolates were collected from July
2008 to April 2013 and represent all MRSP index isolates from each MRSP-positive
dog detected in Norway until April 2013. Geographical distribution of all MRSP
cases was investigated using the ArcGIS 9.3 Software. MRSP was detected from five
(2.6%) healthy dogs, sampled at three different clinics. The isolates grouped
into three sequence types (STs): ST252 (two isolates), ST71 (two isolates) and
ST306 (one isolate). MRSP from dogs sampled at the same animal clinic belonged to
the same ST and produced identical PFGE pattern. The 49 clinical MRSP grouped
into 15 STs; ST258 (n = 17), ST71 (n = 10), and ST305 (n = 4) were the most
prevalent. The MRSP carrier isolates were genetically related to MRSP variants
from dogs with infections as ST306 (from a carrier) is related to ST258. MRSP
ST252, found in two carriers, was also present among the clinical MRSP isolates.
Altogether the MRSP isolates were genetically diverse and MRSP of other lineages
than ST71 continues to disseminate in Norway. Susceptibility testing showed that
MRSP isolates of the ST71 lineage were the most multiresistant. Our study showed
that MRSP could be detected in healthy dogs without infections and with no recent
history of antimicrobial therapy stressing the need for future monitoring,
infection control and prudent use of antimicrobial agents.
PMID- 26423810
TI - 90-90-90: how do we get there?
PMID- 26423811
TI - Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in
HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single
group, clinical trial.
AB - BACKGROUND: Activating the expression of latent virus is an approach that might
form part of an HIV cure. We assessed the ability of the histone deacetylase
inhibitor panobinostat to disrupt HIV-1 latency and the safety of this strategy.
METHODS: In this phase 1/2 clinical trial, we included aviraemic adults with HIV
treated at Aarhus University Hospital, Denmark. Participants received oral
panobinostat (20 mg) three times per week every other week for 8 weeks while
maintaining combination antiretroviral therapy. The primary outcome was change
from baseline of cell-associated unspliced HIV RNA. Secondary endpoints were
safety, plasma HIV RNA, total and integrated HIV DNA, infectious units per
million CD4 T cells, and time to viral rebound during an optional analytical
treatment interruption of antiretroviral therapy. This trial is registered with
ClinicalTrial.gov, number NCT01680094. FINDINGS: We enrolled 15 patients. The
level of cell-associated unspliced HIV RNA increased significantly at all
timepoints when patients were taking panobinostat (p < 0.0001). The median
maximum increase in cell-associated unspliced HIV RNA during panobinostat
treatment was 3.5-fold (range 2.1-14.4). Panobinostat induced plasma viraemia
with an odds ratio of 10.5 (95% CI 2.2-50.3; p = 0.0002) compared with baseline.
We recorded a transient decrease in total HIV DNA, but no cohort-wide reduction
in total HIV DNA, integrated HIV DNA, or infectious units per million. Nine
patients participated in the analytical treatment interruption, median time to
viral rebound was 17 days (range 14-56). Panobinostat was well tolerated. 45
adverse events were reported, but only 16 (all grade 1) were presumed related to
panobinostat. INTERPRETATION: Panobinostat effectively disrupts HIV latency in
vivo and is a promising candidate for future combination clinical trials aimed at
HIV eradication. However, panobinostat did not reduce the number of latently
infected cells and this approach may need to be combined with others to
significantly affect the latent HIV reservoir. FUNDING: The Danish Council for
Strategic Research and Aarhus University.
PMID- 26423812
TI - Tentative first steps to eradicate latent HIV.
PMID- 26423813
TI - Recreational drug use, polydrug use, and sexual behaviour in HIV-diagnosed men
who have sex with men in the UK: results from the cross-sectional ASTRA study.
AB - BACKGROUND: Recreational drug use in men who have sex with men (MSM) is of
concern because it might be linked to the transmission of HIV and other sexually
transmitted infections. Evidence about drug use in HIV-diagnosed MSM in the UK is
limited by representativeness of the study populations. We describe patterns of
drug use and associations with sexual behaviours in HIV-diagnosed MSM in the UK.
METHODS: We used data from the cross-sectional ASTRA study, which recruited
participants aged 18 years or older with HIV from eight HIV outpatient clinics in
the UK between Feb 1, 2011, and Dec 31, 2012. We examined data for MSM, assessing
the prevalence of recreational drug use and polydrug use in the previous 3 months
and associations with sociodemographic and HIV-related factors. We examined the
association of polydrug use with measures of condomless sex in the previous 3
months and with other sexual behaviours. FINDINGS: Our analysis included data for
2248 MSM: 2136 (95%) were gay, 1973 (89%) were white, 1904 (85%) were on
antiretroviral treatment (ART), and 1682 (76%) had a viral load of 50 copies per
mL or lower. 1138 (51%) used recreational drugs in the previous 3 months; 608
(27%) used nitrites, 477 (21%) used cannabis, 460 (21%) used erectile dysfunction
drugs, 453 (20%) used cocaine, 280 (13%) used ketamine, 258 (12%) used 3,4
methylenedioxy-N-methylamphetamine (MDMA), 221 (10%) used gamma-hydroxybutyrate
or gamma-butyrolactone, 175 (8%) used methamphetamine, and 162 (7%) used
mephedrone. In the 1138 individuals who used drugs, 529 (47%) used three or more
drugs and 241 (21%) used five or more. Prevalence of injection drug use was 3% (n
= 68). Drug use was independently associated with younger age (p < 0.0001), not
being religious (p = 0.001), having an HIV-positive stable partner (p = 0.0008),
HIV-serostatus disclosure (p = 0.009), smoking (p < 0.0001), evidence of harmful
alcohol drinking (p = 0.0001), and ART non-adherence (p < 0.0001). Increasing
polydrug use was associated with increasing prevalence of condomless sex
(prevalence range from no drug use to use of five or more drugs was 24% to 78%),
condomless sex with HIV-seroconcordant partners (17% to 69%), condomless sex with
HIV-serodiscordant partners (10% to 25%), and higher-HIV-risk condomless sex
after taking viral load into account (4% to 16%; p <= 0.005 for all).
Associations were similar after adjustment for sociodemographic and HIV-related
factors. Methamphetamine was more strongly associated with higher-HIV-risk
condomless sex than were other commonly used drugs. INTERPRETATION: Polydrug use
is prevalent in HIV-diagnosed MSM and is strongly associated with condomless sex.
Specialist support services for MSM with HIV who use recreational drugs might be
beneficial in the reduction of harm and prevention of ongoing transmission of HIV
and other sexually transmitted infections. FUNDING: National Institute for Health
Research.
PMID- 26423814
TI - Health-related quality-of-life of people with HIV in the era of combination
antiretroviral treatment: a cross-sectional comparison with the general
population.
AB - BACKGROUND: Combination antiretroviral therapy has substantially increased life
expectancy in people living with HIV, but the effects of chronic infection on
health-related quality of life (HRQoL) are unclear. We aimed to compare HRQoL in
people with HIV and the general population. METHODS: We merged two UK cross
sectional surveys: the ASTRA study, which recruited participants aged 18 years or
older with HIV from eight outpatient clinics in the UK between Feb 1, 2011, and
Dec 31, 2012; and the Health Survey for England (HSE) 2011, which measures health
and health-related behaviours in individuals living in a random sample of private
households in England. The ASTRA study has data for 3258 people (response rate
64%) and HSE for 8503 people aged 18 years or older (response rate 66%). HRQoL
was assessed with the Euroqol 5D questionnaire 3 level (EQ-5D-3L) instrument that
measures health on five domains, each with three levels. The responses are scored
on a scale where a value of 1 represents perfect health and a value of 0
represents death, known as the utility score. We used multivariable models to
compare utility scores between the HIV and general population samples with
adjustment for several sociodemographic factors. FINDINGS: 3151 (97%) of 3258 of
participants in ASTRA and 7424 (87%) of 8503 participants in HSE had complete EQ
5D-3L data. The EQ-5D-3L utility score was lower for people with HIV compared
with that in the general population (marginal effect in utility score adjusted
for age, and sex/sexuality -0.11; 95% CI -0.13 to -0.10; p < 0.0001). HRQoL was
lower for people with HIV for all EQ-5D-3L domains, particularly for
anxiety/depression. The difference in utility score was significant after
adjustment for several additional sociodemographic variables (ethnic origin,
education, having children, and smoking status) and was apparent across all CD4
cell count, antiretroviral therapy, and viral load strata, but was greatest for
those people diagnosed with HIV in earlier calendar periods. Reduction in HRQoL
with age was not greater in people with HIV than in the general population
(pinteraction > 0.05). INTERPRETATION: People living with HIV have significantly
lower HRQoL than do the general population, despite most HIV positive individuals
in this study being virologically and immunologically stable. Although this
difference could in part be due to factors other than HIV, this study provides
additional evidence of the loss of health that can be avoided through prevention
of further HIV infections. FUNDING: UK National Institute for Health Research.
PMID- 26423815
TI - Sex, drugs, and HIV: let's avoid panic.
PMID- 26423816
TI - Characterisation of long-term non-progression of HIV-1 infection after
seroconversion: a cohort study.
AB - BACKGROUND: Some individuals remain AIDS-free with a high and stable CD4 cell
count without antiretroviral therapy (ART) for many years. We estimated long-term
progression-free survival after HIV seroconversion and aimed to identify factors
associated with loss of long-term non-progression (LTNP) status. METHODS: For
this cohort study, we used data for individuals with well-estimated dates of HIV
1 seroconversion from the CASCADE Collaboration a network of 28 HIV seroconverter
cohort studies in Europe, Australia, Canada, and sub-Saharan Africa. The first
cohort began enrolling patients in 1979, and for this analysis we used data
pooled in May 1, 2011. We defined non-progression as being HIV-positive without
AIDS, ART-naive, and with CD4 counts of 500 cells per MUL or higher. We defined
LTNP as non-progression during the first 10 years after seroconversion. We used
longitudinal methods to characterise LTNP. FINDINGS: Of the 4979 HIV
seroconverters in our dataset, 3708 (75%) were men. Median time to progression
was 2.07 years (95% CI 1.96-2.17), giving estimated progression-free survivals of
18.4% (17.2-19.6) 5 years, 4.0% (3.6-4.5) 10 years, and 1.4% (0.9-1.5) 15 years
after seroconversion. The rate of progression did not change beyond 10 years
after seroconversion (0.28 [95%CI 0.26-0.31] per person-year at 10 years after
seroconversion, 0.24 [0.19-0.29] per person-year at 15 years, and 0.18 [0.10
0.33] per person-year at 20 years). At 10 years since HIV seroconversion, 283
individuals had LTNP, of whom 202 subsequently lost this status (median time to
loss of status 2.49 years [2.05-2.92]). In univariable analyses, loss of LTNP
status was associated with CD4 cell count at 10 years after seroconversion (p <
0.0001) and HIV RNA load at 10 years after seroconversion (p = 0.005), but not
age (p = 0.544), mode of infection (p = 0.621), sex (p = 0.676), or calendar year
of seroconversion (p = 0.397). In the multivariable analyses, loss of LTNP status
was associated with lower CD4 counts at 10 years after seroconversion (p <
0.0001). After exclusion of CD4 cell counts from the model, higher HIV RNA load
at 10 years after seroconversion was independently associated with loss of LTNP
status (p = 0.009). INTERPRETATION: Progression-free survival is rare. Most
individuals with LTNP eventually lose immunological and clinical control of HIV
infection eventually. FUNDING: European Union Seventh Framework Programme.
PMID- 26423817
TI - Quality of life in chronic HIV infection.
PMID- 26423818
TI - The death of HIV long-term non-progression?
PMID- 26423819
TI - High burden of malaria infection in pregnant women in a rural district of Zambia:
a cross-sectional study.
AB - BACKGROUND: Malaria continues to be a major health problem in low-income
countries. Consequently, malaria control remains a public health priority in
endemic countries such as Zambia. Pregnant women and children under 5 years of
age are among groups at high risk of malaria infection. Malaria infection is
associated with adverse birth outcomes that affect the mother, foetus, and
infant. Infection with HIV has been shown to increase the risk of malaria
infection in pregnancy. The prevalence and the predictors of malaria infection
among pregnant women resident in the Nchelenge District of northern Zambia were
investigated. METHODS: Between November 2013 and April 2014, pregnant women in
the catchment areas of two health centres were recruited during their first
antenatal care visit. HIV testing was conducted as part of routine care. In
addition, blood samples were collected from 1086 participants and tested for
malaria infection using standard microscopy and polymerase chain reaction (PCR)
techniques specific for Plasmodium falciparum. Multivariate logistic regression
were conducted to examine the predictors of malaria infection. RESULTS: The
prevalence of malaria identified by microscopy was 31.8 % (95 % confidence
intervals [CI], 29.0-34.5; N = 1079) and by PCR was 57.8 % (95 % CI, 54.9-60.8; N
= 1074). HIV infection was 13.2 % among women on their first antenatal visit; the
prevalence of malaria detected by PCR among HIV-uninfected and HIV-infected women
was 56.7 % (531/936) and 65.2 % (90/138), respectively. In the final model, the
risk of malaria infection was 81 % higher among pregnant women recruited from
Nchelenge health centre compared to those attending the Kashikishi health centre
(adjusted odds ratio = 1.81; 95 % CI, 1.38-2.37, P < 0.001), and HIV-infected
women across health centres had a 46 % greater risk of malaria infection compared
to HIV-uninfected women (adjusted odds ratio = 1.46; 95 %, 1.00-2.13, P = 0.045).
CONCLUSION: High burden of malaria detected by PCR in these pregnant women
suggests that past prevention efforts have had limited effect. To reduce this
burden of malaria sustainably, there is clear need to strengthen existing
interventions and, possibly, to change approaches so as to improve targeting of
groups most affected by malaria.
PMID- 26423820
TI - Scattered atypical melanocytes with hyperchromatic nuclei in the nail matrix:
diagnostic clue for early subungual melanoma in situ.
AB - BACKGROUND: The lack of highly specific clinical and histopathological criteria
has contributed to the delay in diagnosis of subungual melanoma in situ in its
early stages. METHODS: Eighteen cases of subungual melanoma in situ, the largest
series reported to date, were analyzed to characterize the clinical and
histopathological findings of early stages of subungual melanoma in situ along
with five cases of nail matrix nevus and five cases of subungual lentigo serving
as histologic control. RESULTS: Clinically, longitudinal melanonychia was present
in all 18 cases of subungual melanoma in situ, consisting of irregular dark brown
to black streaks within a brown background with (11 cases) or without
Hutchinson's sign. Histopathologically, variable shaped and sized, hyperchromatic
nuclei surrounded by retraction artifact were present in all cases. Nine cases
showed a significant increase in the number of atypical melanocytes with marked
nuclear atypia, while the rest of the cases showed less noticeable changes in
nail matrix including lower density of melanocytes and/or mild nuclear atypia. In
15 cases, the nuclear enlargement in some of the melanocytes was greater than two
times that of the neighboring matrix cells. In the remaining three cases, the
nuclei were enlarged to a much lesser degree. All cases displayed areas of
haphazard and uneven distribution of solitary melanocytes and, although not
observed in all cases, some degree of pagetoid spread was present in majority of
the cases. In contrast, nail matrix nevi showed well-formed nests consisting of
relatively monomorphous melanocytes with abundant cytoplasm and subungual
lentigos consisted of subtle increase in the number of dendritic melanocytes in
solitary units within the lower layers of the nail matrix. CONCLUSION: Increase
in the number of scattered atypical melanocytes with large hyperchromatic nuclei
in a partial nail matrix may provide a diagnostic clue to subungual melanoma in
situ in concert with its clinical suspicion.
PMID- 26423821
TI - Segmental HOG: new descriptor for glomerulus detection in kidney microscopy
image.
AB - BACKGROUND: The detection of the glomeruli is a key step in the histopathological
evaluation of microscopic images of the kidneys. However, the task of automatic
detection of the glomeruli poses challenges owing to the differences in their
sizes and shapes in renal sections as well as the extensive variations in their
intensities due to heterogeneity in immunohistochemistry staining. Although the
rectangular histogram of oriented gradients (Rectangular HOG) is a widely
recognized powerful descriptor for general object detection, it shows many false
positives owing to the aforementioned difficulties in the context of glomeruli
detection. RESULTS: A new descriptor referred to as Segmental HOG was developed
to perform a comprehensive detection of hundreds of glomeruli in images of whole
kidney sections. The new descriptor possesses flexible blocks that can be
adaptively fitted to input images in order to acquire robustness for the
detection of the glomeruli. Moreover, the novel segmentation technique employed
herewith generates high-quality segmentation outputs, and the algorithm is
assured to converge to an optimal solution. Consequently, experiments using real
world image data revealed that Segmental HOG achieved significant improvements in
detection performance compared to Rectangular HOG. CONCLUSION: The proposed
descriptor for glomeruli detection presents promising results, and it is expected
to be useful in pathological evaluation.
PMID- 26423822
TI - Stratifying the outcome after neoadjuvant treatment using pathological response
classification by the Japanese Breast Cancer Society.
AB - BACKGROUNDS: Neoadjuvant chemotherapy (NAC) is one of the standard treatment for
patients with operable and locally advanced breast cancer. Pathological response
after NAC has been assessed according to the Japanese Breast Cancer Society
(JBCS) classification in Japan. This classification that was first established in
1998 and revised in 2007 has been used in routine clinical practice in Japan. In
the present study, we investigated whether the assessment of pathological
response according to this classification could stratify the long-term outcome of
patients with breast cancer. METHODS: Patients with breast cancer who had
received neoadjuvant chemotherapy between January 2003 and December 2005 in 6
hospitals participating in this study were identified. Patients whose response
was judged to be Grade 2 was reassessed into Grades 2a and 2b according to the
updated JBCS classification revised in 2007. Then, the association of
pathological response and recurrence-free survival (RFS) was analyzed. RESULTS:
635 patients received NAC and 154 relapses (24 %) were observed during a median
follow-up of 41.5 months (range 4.2-69.5 months). There was a statistically
significant difference in RFS among each pathological response. 5-year RFS of
patients with Grade 3 without residual ductal carcinoma in situ was 94 %. 5-year
RFS were 88 % in Grade 3, 95 % in Grade 2b, 80 % in Grade 2a, 73 % in Grade 1b,
67 % in Grade 1a, 59 % in Grade 0, respectively. CONCLUSIONS: An outcome could be
stratified by assessing tumor burden following NAC according to the JBCS
classification.
PMID- 26423824
TI - Locking compression plate stabilization of 20 distal radial and ulnar fractures
in toy and miniature breed dogs.
AB - OBJECTIVE: To evaluate retrospectively the effectiveness of the Locking
Compression Plate(r) (LCP), in the form of either a straight or notched head T
plate, for the treatment of fractures of the distal radius and ulna in a series
of 20 toy and miniature breed dogs. METHODS: The medical records of toy and
miniature breed dogs (<6 kg), greater than six months of age, with fractures of
the distal radius and ulna from two veterinary hospitals were reviewed. The
inclusion criteria included: fractures of the distal 1/3 of the radius and ulna
and repair with open reduction and internal fixation utilizing an LCP (straight
or notched head T-plate). RESULTS: Twenty fractures (20 dogs) satisfied the
inclusion criteria; eight straight and 12 notched head T-plates were used, either
2.0 mm (n = 13) or 2.4 mm (n = 7). Hybrid fixation was performed in all dogs in
one or both fragments. Mean time to radiographic union was 6.9 +/- 2.5 weeks
(range: 4-12 weeks) in 18/20 dogs with radiographic follow-up. One complication
was observed: infection that resolved with antibiotic medication and implant
removal. No other major complications occurred by the time of last follow-up. In
all cases (mean follow-up: 15 +/- 7 months), the reported limb function as
evaluated by the referring veterinarian or owner was excellent. CLINICAL
SIGNIFICANCE: The LCP, used as a hybrid construct for the treatment of distal
radial and ulnar fractures was shown to yield excellent clinical results with
both uncomplicated healing and excellent functional outcomes in this series of
toy and miniature breed dogs.
PMID- 26423823
TI - Positively biased self-perceptions of peer acceptance and subtypes of aggression
in children.
AB - There is a growing body of research linking children's positively biased self
perceptions with higher levels of aggression. This study extended this area of
research by examining prospective associations of positively biased self
perceptions of peer acceptance with overt and relational aggression. In addition,
moderating effects of peer rejection were examined to test the "disputed
overestimation hypothesis," which posits that the link between bias and
aggression is limited to children who are rejected by their peers. Using a two
wave longitudinal design, measures of peer-rated and self-perceived peer
acceptance and peer-rated overt and relational aggression were obtained for 712
children in 3rd through 5th grades (386 girls and 326 boys). Positively biased
perceptions led to increases in relational, but not overt, aggression. This
pattern was observed even when the effects of gender, race, peer rejection, and
overt aggression on relational aggression were controlled. Contrary to the
disputed overestimation hypothesis, the prospective associations between bias and
aggression did not vary as a function of children's peer rejection status, thus
supporting the view that positive bias predicts future aggressive behavior,
regardless of social status. The results are discussed in terms of the
comparability with previous findings and practical implications.
PMID- 26423825
TI - Imprecision Investigation and Analysis of Routine Chemistry in China.
AB - BACKGROUND: This study aims to investigate the imprecision of internal quality
control of routine chemistry analytes so that we can have an overall knowledge of
imprecision level of measurement in laboratories in China. METHODS: The internal
quality control information including two kinds of coefficient of variations
(CVs) of 22 analytes were collected via an on-line questionnaire. Then, the
percentages of laboratories meeting the quality requirement for each analyte were
calculated according to five imprecision criteria. RESULTS: Among these 22
analytes, creatine kinase got the most satisfied result, the percentages of
laboratories whose current CV met 1/3 total allowable error (1/3TEa), 1/4TEa, and
the specifications based on biological variation were 99.3%, 95.9%, 99.6%, 99.9%,
and 90.6%, respectively, while Na got the lowest satisfaction rate according to
these specifications, which were 4.15%, 22.4%, 4.2%, 9.0%, and 1.3%,
respectively. From an overall perspective, most of the 22 analytes got a
satisfied result when applying the criteria defined by CLIA'88, while only a
small amount of laboratories can meet the requirement when applying the
specifications derived from biological variation. CONCLUSIONS: There is huge
space for us to enhance and substantial effort is needed in improving and
implementing quality management in China.
PMID- 26423826
TI - A trial to find appropriate animal models of dichloropropane-induced
cholangiocarcinoma based on the hepatic distribution of glutathione S
transferases.
AB - OBJECTIVES: It has been reported that 1,2-Dichloropropane (DCP) induced
cholangiocarcinoma (CCA) in offset color proof-printing workers. However,
exposure to DCP by inhalation or gavage for 2 year did not induce CCA in mice and
rats. The present study mapped the hepatic distribution of GST, which is known to
activate dihalogenated alkanes, and proliferative and fibrotic changes in bile
ducts in various species to find the most appropriate animal model of DCP-induced
CCA. METHODS: First, 12 each of C57BL/6J mice, Balb/cA mice, F344 rats, Syrian
hamsters, and guinea pigs were divided into four equal groups and exposed to DCP
at 0, 300, 1,000, or 3,000 ppm 8 hours/day for 7 days. Second, 32 Balb/cA mice
and 32 Syrian hamsters were each divided into four equal groups and exposed to
DCP at 0, 200, 400, and 800 ppm 6 hours/day for 14 days. After the last exposure,
the animals were decapitated, and the livers were dissected out for
histopathological evaluation. Immunostaining was conducted to determine the
distribution of GSTT1, GSTM1, and GSTPi, as well as the expression of
proliferation marker Ki67. RESULTS: GSTT1, GSTM1, and GSTPi were expressed in
both hepatocytes and bile duct cells in all control and exposed animals. There
was no clear difference in the expression of Ki67 between the exposed groups and
the control. No fibrotic changes were observed in any species or strains
examined. CONCLUSIONS: Expression of GSTT1 or other GST isozymes might not
explain the difference in sensitivity of hepatocytes and the bile duct to DCP
between humans and rodents.
PMID- 26423827
TI - Determinants of workplace violence against clinical physicians in hospitals.
AB - OBJECTIVES: Workplace violence in the health sector is a worldwide concern.
Physicians play an essential role in health-care teamwork; thus, understanding
how organizational factors influence workplace violence against physicians is
critical. METHODS: A total of 189 physicians from three public hospitals and one
private hospital in Northern Taiwan completed a survey, and the response rate was
47.1%. This study was approved by the institutional review board of each
participating hospital. The 189 physicians were selected from the Taipei area,
Taiwan. RESULTS: The results showed that 41.5% of the respondents had received at
least one workplace-related physical or verbal violent threat, and that 9.8% of
the respondents had experienced at least one episode of sexual harassment in the
3 months before the survey. Logistic regression analysis revealed that physicians
in psychiatry or emergency medicine departments received more violent threats and
sexual harassment than physicians in other departments. Furthermore, physicians
with a lower workplace safety climate (OR=0.89; 95% CI=0.81-0.98) and more job
demands (OR=1.15; 95% CI=1.02-1.30) were more likely to receive violent threats.
CONCLUSIONS: This study found that workplace violence was associated with job
demands and the workplace safety climate. Therefore, determining how to develop a
workplace safety climate and ensure a safe job environment for physicians is a
crucial management policy issue for health-care systems.
PMID- 26423828
TI - Associations of neighborhood-level workplace violence with workers' mental
distress problems: a multilevel analysis of Taiwanese employees.
AB - OBJECTIVE: Workplace violence is known to pose mental health risks. However,
whether or not workplace violence in a surrounding area might further increase
the risk of mental distress in workers has rarely been examined. METHODS: The
study subjects were 9,393 male and 7,716 female employees who participated in a
nationwide survey in 2010. Their personal experiences of workplace violence over
the past 1 year were ascertained by a standardized questionnaire. Also assessed
were their psychosocial work characteristics and mental distress problems.
Neighborhood-level workplace violence was computed based on aggregated data at
the county level and was categorized into low-, medium-, and high-level
categories. Multilevel logistic regression models were constructed to examine the
associations between neighborhood-level workplace violence and individual-level
mental distress problems, with adjustment of individual-level experience of
workplace violence. FINDINGS: The neighborhood-level prevalence of workplace
violence ranged from 4.7 to 14.7% in men and from 6.4 to 14.8% in women across 22
counties. As compared with those who live in counties of the lowest tertile of
workplace violence, female workers who lived in counties of the highest tertile
of workplace violence had a 1.72-fold increased risk for mental distress problems
after controlling for individual experience of workplace violence and other
psychosocial work characteristics. CONCLUSION: Neighborhood-level workplace
violence was associated with poor mental health in female workers. Preventative
strategies targeting workplace violence should pay attention to neighborhood
factors and gender-specific effects that might influence societal tolerance of
abusive work practices and workers' vulnerability to mental health impacts of
workplace violence.
PMID- 26423829
TI - Pancreatic cysts suspected to be branch duct intraductal papillary mucinous
neoplasm without concerning features have low risk for development of pancreatic
cancer.
AB - BACKGROUND: The risk of developing pancreatic cancer is uncertain in patients
with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD
IPMN) based on the "high-risk stigmata" or "worrisome features" criteria proposed
in the 2012 international consensus guidelines ("Fukuoka criteria"). METHODS:
Retrospective case series involving patients referred for endoscopic ultrasound
(EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent
with BD-IPMN. Rates of pancreatic cancer occurring at any location in the
pancreas were compared between groups of patients with one or more Fukuoka
criteria ("Highest-Risk Group", HRG) and those without these criteria ("Lowest
Risk Group", LRG). RESULTS: After exclusions, 661 patients comprised the final
cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years
and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred
in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate
surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and
exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative
incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001).
CONCLUSIONS: This study supports using Fukuoka criteria to stratify the immediate
and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of
pancreatic cancer was highest during the first year and occurred exclusively in
those with "high-risk stigmata" or "worrisome features" criteria. After the first
year all BD-IPMN continued to have a low but persistent cancer risk.
PMID- 26423832
TI - India has low doctor to patient ratio, study finds.
PMID- 26423830
TI - Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative
myeloproliferative neoplasms.
AB - Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic
diseases characterized by clonal hematopoiesis and hyperproliferation of
terminally differentiated myeloid cells. The disease is driven by somatic
mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases,
whereas the remaining cases are termed "triple negative." We aimed to identify
the disease-causing mutations in the triple-negative cases of ET and PMF by
applying whole-exome sequencing (WES) on paired tumor and control samples from 8
patients. We found evidence of clonal hematopoiesis in 5 of 8 studied cases based
on clonality analysis and presence of somatic genetic aberrations. WES identified
somatic mutations in 3 of 8 cases. We did not detect any novel recurrent somatic
mutations. In 3 patients with clonal hematopoiesis analyzed by WES, we identified
a somatic MPL-S204P, a germline MPL-V285E mutation, and a germline JAK2-G571S
variant. We performed Sanger sequencing of the entire coding region of MPL in 62,
and of JAK2 in 49 additional triple-negative cases of ET or PMF. New somatic
(T119I, S204F, E230G, Y591D) and 1 germline (R321W) MPL mutation were detected.
All of the identified MPL mutations were gain-of-function when analyzed in
functional assays. JAK2 variants were identified in 5 of 57 triple-negative cases
analyzed by WES and Sanger sequencing combined. We could demonstrate that JAK2
V625F and JAK2-F556V are gain-of-function mutations. Our results suggest that
triple-negative cases of ET and PMF do not represent a homogenous disease entity.
Cases with polyclonal hematopoiesis might represent hereditary disorders.
PMID- 26423833
TI - Antisense oligonucleotide drugs for Duchenne muscular dystrophy: how far have we
come and what does the future hold?
PMID- 26423834
TI - The 2015 International Psychogeriatric Association Junior Research Awards in
Psychogeriatrics.
PMID- 26423836
TI - Density-based parallel skin lesion border detection with webCL.
AB - BACKGROUND: Dermoscopy is a highly effective and noninvasive imaging technique
used in diagnosis of melanoma and other pigmented skin lesions. Many aspects of
the lesion under consideration are defined in relation to the lesion border. This
makes border detection one of the most important steps in dermoscopic image
analysis. In current practice, dermatologists often delineate borders through a
hand drawn representation based upon visual inspection. Due to the subjective
nature of this technique, intra- and inter-observer variations are common.
Because of this, the automated assessment of lesion borders in dermoscopic images
has become an important area of study. METHODS: Fast density based skin lesion
border detection method has been implemented in parallel with a new parallel
technology called WebCL. WebCL utilizes client side computing capabilities to use
available hardware resources such as multi cores and GPUs. Developed WebCL
parallel density based skin lesion border detection method runs efficiently from
internet browsers. RESULTS: Previous research indicates that one of the highest
accuracy rates can be achieved using density based clustering techniques for skin
lesion border detection. While these algorithms do have unfavorable time
complexities, this effect could be mitigated when implemented in parallel. In
this study, density based clustering technique for skin lesion border detection
is parallelized and redesigned to run very efficiently on the heterogeneous
platforms (e.g. tablets, SmartPhones, multi-core CPUs, GPUs, and fully-integrated
Accelerated Processing Units) by transforming the technique into a series of
independent concurrent operations. Heterogeneous computing is adopted to support
accessibility, portability and multi-device use in the clinical settings. For
this, we used WebCL, an emerging technology that enables a HTML5 Web browser to
execute code in parallel for heterogeneous platforms. We depicted WebCL and our
parallel algorithm design. In addition, we tested parallel code on 100 dermoscopy
images and showed the execution speedups with respect to the serial version.
Results indicate that parallel (WebCL) version and serial version of density
based lesion border detection methods generate the same accuracy rates for 100
dermoscopy images, in which mean of border error is 6.94%, mean of recall is
76.66%, and mean of precision is 99.29% respectively. Moreover, WebCL version's
speedup factor for 100 dermoscopy images' lesion border detection averages around
~491.2. CONCLUSIONS: When large amount of high resolution dermoscopy images
considered in a usual clinical setting along with the critical importance of
early detection and diagnosis of melanoma before metastasis, the importance of
fast processing dermoscopy images become obvious. In this paper, we introduce
WebCL and the use of it for biomedical image processing applications. WebCL is a
javascript binding of OpenCL, which takes advantage of GPU computing from a web
browser. Therefore, WebCL parallel version of density based skin lesion border
detection introduced in this study can supplement expert dermatologist, and aid
them in early diagnosis of skin lesions. While WebCL is currently an emerging
technology, a full adoption of WebCL into the HTML5 standard would allow for this
implementation to run on a very large set of hardware and software systems. WebCL
takes full advantage of parallel computational resources including multi-cores
and GPUs on a local machine, and allows for compiled code to run directly from
the Web Browser.
PMID- 26423837
TI - Asymmetric synthesis of syn-propargylamines and unsaturated beta-amino acids
under Bronsted base catalysis.
AB - Propargylamines are important intermediates for the synthesis of polyfunctional
amino derivatives and natural products and biologically active compounds. The
classic method of synthesizing chiral propargylamines involves the asymmetric
alkynylation of imines. Here, we report a significant advance in the catalytic
asymmetric Mannich-type synthesis of propargylamines through catalytic asymmetric
addition of carbon nucleophiles to C-alkynyl imines, culminating in a highly syn
selective catalytic asymmetric Mannich reaction of C-alkynyl imines that provide
syn-configured propargylamines with two adjacent stereogenic centres and a
transition metal-free organocatalytic asymmetric approach to beta-alkynyl-beta
amino acids with high efficiency and practicality, via a chiral Bronsted base
catalysed asymmetric Mannich-type reaction of in situ generated challenging N-Boc
C-alkynyl imines from previously unreported C-alkynyl N-Boc-N,O-acetals, with
alpha-substituted beta-keto esters and less-acidic malonate (thio)esters as
nucleophiles, respectively. A catalytic activation strategy is also disclosed,
which may have broad implications for use in catalysis and synthesis.
PMID- 26423835
TI - Attenuation of p38alpha MAPK stress response signaling delays the in vivo aging
of skeletal muscle myofibers and progenitor cells.
AB - Functional competence and self-renewal of mammalian skeletal muscle myofibers and
progenitor cells declines with age. Progression of the muscle aging phenotype
involves the decline of juvenile protective factorsi.e., proteins whose
beneficial functions translate directly to the quality of life, and self-renewal
of progenitor cells. These characteristics occur simultaneously with the age
associated increase of p38alpha stress response signaling. This suggests that the
maintenance of low levels of p38alpha activity of juvenile tissues may delay or
attenuate aging. We used the dominant negative haploinsufficient p38alpha mouse
(DN-p38alpha(AF/+)) to demonstrate that in vivo attenuation of p38alpha activity
in the gastrocnemius of the aged mutant delays age-associated processes that
include: a) the decline of the juvenile protective factors, BubR1, aldehyde
dehydrogenase 1A (ALDH1A1), and aldehyde dehydrogenase 2 (ALDH2); b) attenuated
expression of p16(Ink4a) and p19(Arf) tumor suppressor genes of the Cdkn2a locus;
c) decreased levels of hydroxynonenal protein adducts, expression of COX2 and
iNOS; d) decline of the senescent progenitor cell pool level and d) the loss of
gastrocnemius muscle mass. We propose that elevated P-p38alpha activity promotes
skeletal muscle aging and that the homeostasis of p38alpha impacts the
maintenance of a beneficial healthspan.
PMID- 26423838
TI - Mass spectrometric identification and toxicity assessment of degraded products of
aflatoxin B1 and B2 by Corymbia citriodora aqueous extracts.
AB - This study explores the detoxification potential of Corymbia citriodora plant
extracts against aflatoxin B1 and B2 (AFB1; 100 MUg L(-1) and AFB2; 50 MUg L(-1))
in In vitro and In vivo assays. Detoxification was qualitatively and
quantitatively analyzed by TLC and HPLC, respectively. The study was carried out
by using different parameters of optimal temperature, pH and incubation time
period. Results indicated that C. citriodora leaf extract(s) more effectively
degrade AFB1 and AFB2 i.e. 95.21% and 92.95% respectively than C. citriodora
branch extract, under optimized conditions. The structural elucidation of
degraded toxin products was done by LCMS/MS analysis. Ten degraded products of
AFB1 and AFB2 and their fragmentation pathways were proposed based on molecular
formulas and MS/MS spectra. Toxicity of these degraded products was significantly
reduced as compared to that of parent compounds because of the removal of double
bond in the terminal furan ring. The biological toxicity of degraded toxin was
further analyzed by brine shrimps bioassay, which showed that only 17.5%
mortality in larvae was recorded as compared to untreated toxin where 92.5%
mortality was observed after 96hr of incubation. Therefore, our finding suggests
that C. citriodora leaf extract can be used as an effective tool for the
detoxification of aflatoxins.
PMID- 26423839
TI - Social interactions elicit rapid shifts in functional connectivity in the social
decision-making network of zebrafish.
AB - According to the social decision-making (SDM) network hypothesis, SDM is encoded
in a network of forebrain and midbrain structures in a distributed and dynamic
fashion, such that the expression of a given social behaviour is better reflected
by the overall profile of activation across the different loci rather than by the
activity of a single node. This proposal has the implicit assumption that SDM
relies on integration across brain regions, rather than on regional
specialization. Here we tested the occurrence of functional localization and of
functional connectivity in the SDM network. For this purpose we used zebrafish to
map different social behaviour states into patterns of neuronal activity, as
indicated by the expression of the immediate early genes c-fos and egr-1, across
the SDM network. The results did not support functional localization, as some
loci had similar patterns of activity associated with different social behaviour
states, and showed socially driven changes in functional connectivity. Thus, this
study provides functional support to the SDM network hypothesis and suggests that
the neural context in which a given node of the network is operating (i.e. the
state of its interconnected areas) is central to its functional relevance.
PMID- 26423840
TI - Dopamine is a key regulator in the signalling pathway underlying predator-induced
defences in Daphnia.
AB - The waterflea Daphnia is a model to investigate the genetic basis of phenotypic
plasticity resulting from one differentially expressed genome. Daphnia develops
adaptive phenotypes (e.g. morphological defences) thwarting predators, based on
chemical predator cue perception. To understand the genomic basis of phenotypic
plasticity, the description of the precedent cellular and neuronal mechanisms is
fundamental. However, key regulators remain unknown. All neuronal and endocrine
stimulants were able to modulate but not induce defences, indicating a pathway of
interlinked steps. A candidate able to link neuronal with endocrine responses is
the multi-functional amine dopamine. We here tested its involvement in trait
formation in Daphnia pulex and Daphnia longicephala using an induction assay
composed of predator cues combined with dopaminergic and cholinergic stimulants.
The mere application of both stimulants was sufficient to induce morphological
defences. We determined dopamine localization in cells found in close association
with the defensive trait. These cells serve as centres controlling divergent
morphologies. As a mitogen and sclerotization agent, we anticipate that dopamine
is involved in proliferation and structural formation of morphological defences.
Furthermore, dopamine pathways appear to be interconnected with endocrine
pathways, and control juvenile hormone and ecdysone levels. In conclusion,
dopamine is suggested as a key regulator of phenotypic plasticity.
PMID- 26423841
TI - An exceptionally preserved Late Devonian actinopterygian provides a new model for
primitive cranial anatomy in ray-finned fishes.
AB - Actinopterygians (ray-finned fishes) are the most diverse living osteichthyan
(bony vertebrate) group, with a rich fossil record. However, details of their
earliest history during the middle Palaeozoic (Devonian) 'Age of Fishes' remains
sketchy. This stems from an uneven understanding of anatomy in early
actinopterygians, with a few well-known species dominating perceptions of
primitive conditions. Here we present an exceptionally preserved ray-finned fish
from the Late Devonian (Middle Frasnian, ca 373 Ma) of Pas-de-Calais, northern
France. This new genus is represented by a single, three-dimensionally preserved
skull. CT scanning reveals the presence of an almost complete braincase along
with near-fully articulated mandibular, hyoid and gill arches. The neurocranium
differs from the coeval Mimipiscis in displaying a short aortic canal with a
distinct posterior notch, long grooves for the lateral dorsal aortae, large
vestibular fontanelles and a broad postorbital process. Identification of similar
but previously unrecognized features in other Devonian actinopterygians suggests
that aspects of braincase anatomy in Mimipiscis are apomorphic, questioning its
ubiquity as stand-in for generalized actinopterygian conditions. However, the
gill skeleton of the new form broadly corresponds to that of Mimipiscis, and adds
to an emerging picture of primitive branchial architecture in crown gnathostomes.
The new genus is recovered in a polytomy with Mimiidae and a subset of Devonian
and stratigraphically younger actinopterygians, with no support found for a
monophyletic grouping of Moythomasia with Mimiidae.
PMID- 26423842
TI - Multimodal signalling in the North American barn swallow: a phenotype network
approach.
AB - Complex signals, involving multiple components within and across modalities, are
common in animal communication. However, decomposing complex signals into traits
and their interactions remains a fundamental challenge for studies of phenotype
evolution. We apply a novel phenotype network approach for studying complex
signal evolution in the North American barn swallow (Hirundo rustica
erythrogaster). We integrate model testing with correlation-based phenotype
networks to infer the contributions of female mate choice and male-male
competition to the evolution of barn swallow communication. Overall, the best
predictors of mate choice were distinct from those for competition, while
moderate functional overlap suggests males and females use some of the same
traits to assess potential mates and rivals. We interpret model results in the
context of a network of traits, and suggest this approach allows researchers a
more nuanced view of trait clustering patterns that informs new hypotheses about
the evolution of communication systems.
PMID- 26423843
TI - Early development of rostrum saw-teeth in a fossil ray tests classical theories
of the evolution of vertebrate dentitions.
AB - In classical theory, teeth of vertebrate dentitions evolved from co-option of
external skin denticles into the oral cavity. This hypothesis predicts that
ordered tooth arrangement and regulated replacement in the oral dentition were
also derived from skin denticles. The fossil batoid ray Schizorhiza stromeri
(Chondrichthyes; Cretaceous) provides a test of this theory. Schizorhiza
preserves an extended cartilaginous rostrum with closely spaced, alternating saw
teeth, different from sawfish and sawsharks today. Multiple replacement teeth
reveal unique new data from micro-CT scanning, showing how the 'cone-in-cone'
series of ordered saw-teeth sets arrange themselves developmentally, to become
enclosed by the roots of pre-existing saw-teeth. At the rostrum tip, newly
developing saw-teeth are present, as mineralized crown tips within a vascular,
cartilaginous furrow; these reorient via two 90 degrees rotations then relocate
laterally between previously formed roots. Saw-tooth replacement slows mid
rostrum where fewer saw-teeth are regenerated. These exceptional developmental
data reveal regulated order for serial self-renewal, maintaining the saw edge
with ever-increasing saw-tooth size. This mimics tooth replacement in
chondrichthyans, but differs in the crown reorientation and their enclosure
directly between roots of predecessor saw-teeth. Schizorhiza saw-tooth
development is decoupled from the jaw teeth and their replacement, dependent on a
dental lamina. This highly specialized rostral saw, derived from diversification
of skin denticles, is distinct from the dentition and demonstrates the potential
developmental plasticity of skin denticles.
PMID- 26423844
TI - Convergent evolution of vascular optimization in kelp (Laminariales).
AB - Terrestrial plants and mammals, although separated by a great evolutionary
distance, have each arrived at a highly conserved body plan in which universal
allometric scaling relationships govern the anatomy of vascular networks and key
functional metabolic traits. The universality of allometric scaling suggests that
these phyla have each evolved an 'optimal' transport strategy that has been
overwhelmingly adopted by extant species. To truly evaluate the dominance and
universality of vascular optimization, however, it is critical to examine other,
lesser-known, vascularized phyla. The brown algae (Phaeophyceae) are one such
group--as distantly related to plants as mammals, they have convergently evolved
a plant-like body plan and a specialized phloem-like transport network. To
evaluate possible scaling and optimization in the kelp vascular system, we
developed a model of optimized transport anatomy and tested it with measurements
of the giant kelp, Macrocystis pyrifera, which is among the largest and most
successful of macroalgae. We also evaluated three classical allometric
relationships pertaining to plant vascular tissues with a diverse sampling of
kelp species. Macrocystis pyrifera displays strong scaling relationships between
all tested vascular parameters and agrees with our model; other species within
the Laminariales display weak or inconsistent vascular allometries. The lack of
universal scaling in the kelps and the presence of optimized transport anatomy in
M. pyrifera raises important questions about the evolution of optimization and
the possible competitive advantage conferred by optimized vascular systems to
multicellular phyla.
PMID- 26423845
TI - The alignment between phenotypic plasticity, the major axis of genetic variation
and the response to selection.
AB - Phenotypic plasticity is the ability of a genotype to produce more than one
phenotype in order to match the environment. Recent theory proposes that the
major axis of genetic variation in a phenotypically plastic population can align
with the direction of selection. Therefore, theory predicts that plasticity
directly aids adaptation by increasing genetic variation in the direction
favoured by selection and reflected in plasticity. We evaluated this theory in
the freshwater crustacean Daphnia pulex, facing predation risk from two
contrasting size-selective predators. We estimated plasticity in several life
history traits, the G matrix of these traits, the selection gradients on
reproduction and survival, and the predicted responses to selection. Using these
data, we tested whether the genetic lines of least resistance and the predicted
response to selection aligned with plasticity. We found predator environment
specific G matrices, but shared genetic architecture across environments resulted
in more constraint in the G matrix than in the plasticity of the traits,
sometimes preventing alignment of the two. However, as the importance of survival
selection increased, the difference between environments in their predicted
response to selection increased and resulted in closer alignment between the
plasticity and the predicted selection response. Therefore, plasticity may indeed
aid adaptation to new environments.
PMID- 26423846
TI - Wildlife-friendly farming increases crop yield: evidence for ecological
intensification.
AB - Ecological intensification has been promoted as a means to achieve
environmentally sustainable increases in crop yields by enhancing ecosystem
functions that regulate and support production. There is, however, little direct
evidence of yield benefits from ecological intensification on commercial farms
growing globally important foodstuffs (grains, oilseeds and pulses). We
replicated two treatments removing 3 or 8% of land at the field edge from
production to create wildlife habitat in 50-60 ha patches over a 900 ha
commercial arable farm in central England, and compared these to a business as
usual control (no land removed). In the control fields, crop yields were reduced
by as much as 38% at the field edge. Habitat creation in these lower yielding
areas led to increased yield in the cropped areas of the fields, and this
positive effect became more pronounced over 6 years. As a consequence, yields at
the field scale were maintained--and, indeed, enhanced for some crops--despite
the loss of cropland for habitat creation. These results suggested that over a 5
year crop rotation, there would be no adverse impact on overall yield in terms of
monetary value or nutritional energy. This study provides a clear demonstration
that wildlife-friendly management which supports ecosystem services is compatible
with, and can even increase, crop yields.
PMID- 26423847
TI - Artificial light at night desynchronizes strictly seasonal reproduction in a wild
mammal.
AB - Change in day length is an important cue for reproductive activation in
seasonally breeding animals to ensure that the timing of greatest maternal
investment (e.g. lactation in mammals) coincides with favourable environmental
conditions (e.g. peak productivity). However, artificial light at night has the
potential to interfere with the perception of such natural cues. Following a 5
year study on two populations of wild marsupial mammals exposed to different
night-time levels of anthropogenic light, we show that light pollution in urban
environments masks seasonal changes in ambient light cues, suppressing melatonin
levels and delaying births in the tammar wallaby. These results highlight a
previously unappreciated relationship linking artificial light at night with
induced changes in mammalian reproductive physiology, and the potential for
larger-scale impacts at the population level.
PMID- 26423848
TI - Spring or string: does tendon elastic action influence wing muscle mechanics in
bat flight?
AB - Tendon springs influence locomotor movements in many terrestrial animals, but
their roles in locomotion through fluids as well as in small-bodied mammals are
less clear. We measured muscle, tendon and joint mechanics in an elbow extensor
of a small fruit bat during ascending flight. At the end of downstroke, the
tendon was stretched by elbow flexion as the wing was folded. At the end of
upstroke, elastic energy was recovered via tendon recoil and extended the elbow,
contributing to unfurling the wing for downstroke. Compared with a hypothetical
'string-like' system lacking series elastic compliance, the tendon spring
conferred a 22.5% decrease in muscle fascicle strain magnitude. Our findings
demonstrate tendon elastic action in a small flying mammal and expand our
understanding of the occurrence and action of series elastic actuator mechanisms
in fluid-based locomotion.
PMID- 26423849
TI - Peer review comments on drug trials submitted to medical journals differ
depending on sponsorship, results and acceptance: a retrospective cohort study.
AB - OBJECTIVE: During peer review, submitted manuscripts are scrutinised by
independent experts to assist journal editors in their decision-making and to
help improve the quality of articles. In this retrospective cohort study, peer
review comments for drug trials submitted to medical journals were analysed to
investigate whether there is a relation between the content of these comments and
sponsorship, direction of results and decision about acceptance. DESIGN/SETTING:
Descriptive content analysis of reviewer comments made on manuscripts on drug
trials submitted to eight medical journals (January 2010-April 2012). For each
manuscript, the number of reviewers, decision about acceptance, sponsorship and
direction of results were extracted. Reviewer comments were classified using a
predefined checklist. RESULTS: Reviewer reports for 246 manuscripts were
assessed. Industry-sponsored trials were more likely to receive comments about
lack of novelty (8.9%) than industry-supported (2.5%) and non-industry trials
(6.1%, overall p=0.038). Non-industry trials more often received comments about
poor experimental design (69.7%) than industry-supported (58.8%) and industry
sponsored trials (52.9%, overall p=0.019). Non-industry trials were also more
likely to receive comments regarding inappropriate statistical analyses (28.4%)
than industry-supported (23.5%) and industry-sponsored trials (15.1%, overall
p=0.006). Manuscripts with negative results were more likely to receive comments
about inappropriate conclusions (29.3%) than those with positive results (18.9%,
p=0.010). Rejected manuscripts had more often received comments on the research
question not being clinically relevant (7.8%) than accepted manuscripts (1.6%,
p=0.002), and also on lack of novelty (8.3% vs 2.6%, p=0.008) and poor
experimental design (68.6% vs 50.5%, p<0.001). CONCLUSIONS: Reviewers identified
fewer shortcomings regarding design and statistical analyses in industry-related
trials, but commented more often on a lack of novelty in industry-sponsored
trials. Negative trial results did not significantly influence the nature of
comments other than appropriateness of the conclusion. Manuscript acceptance was
primarily related to the research question and methodological robustness of
studies.
PMID- 26423850
TI - Process evaluation of the impact and acceptability of a polypill for prevention
of cardiovascular disease.
AB - IMPORTANCE: The Use of a Multidrug Pill In Reducing cardiovascular Events
(UMPIRE) trial has shown improved adherence with the use of a polypill strategy
when compared with usual medications for cardiovascular disease (CVD) prevention.
To advance from efficacy to impact, we need a better understanding of why and how
such a strategy might be deployed in complex health systems. OBJECTIVE: To
understand, from the perspective of UMPIRE trial participants and professionals,
how and why a polypill strategy improves adherence compared with usual care, why
improvement is greater in some subgroups, and to explore the acceptability of a
polypill strategy among trial participants and healthcare professionals. DESIGN,
SETTING AND PARTICIPANTS: A preplanned process evaluation, based on qualitative
interviews, was conducted with a subsample of 102 trial participants and 41
healthcare professionals at the end of the UMPIRE trial in India and Europe.
RESULTS: Most patients contrasted the simplicity of the polypill with usual
medications that they found complex and, for many in India, expensive. Patients
with low baseline adherence struggled most with complex medication lists, and
those without established disease described less motivation to adhere when
compared with people who had already been diagnosed with CVD; people in the
latter group had already undertaken self-directed measures to adhere to CVD
preventive medicines prior to entering the trial. Taking medication was one of
many adaptations described by patients; these included dietary changes, stopping
smoking and maintaining exercise. Most patients liked the polypill strategy,
although some participants and health professionals were concerned that it would
provide less tailored therapy for individual needs. CONCLUSIONS: Adherence to
treatment lists with multiple medications is complex and influenced by several
factors. Simplifying medication by using a once-daily polypill is one approach to
CVD prevention that may enhance adherence. Prescribers should also consider the
wide variety of adjustments that individuals need to make to cope with daily
medication.
PMID- 26423851
TI - Efficacy of advice from healthcare professionals to pregnant women on avoiding
constrictive clothing around the trunk: a study protocol for a randomised
controlled trial.
AB - INTRODUCTION: As a component of midwife care, eliminating clothing that
constricts the trunk has been shown to markedly elevate the uterine fundus,
soften the uterus and abdomen, and reduce the abdominal wall tension in women
admitted to hospital due to the risk of miscarriage or premature delivery.
However, no prospective study has conclusively verified the efficacy of avoiding
constrictive clothes around the trunk in pregnant women. We aim to verify the
efficacy of instructing pregnant women to wear loose clothing that does not
constrict the trunk to reduce the risk of premature birth and improve quality of
life (QoL) during pregnancy. METHODS AND ANALYSIS: We will conduct a randomised
controlled trial of pregnant women scheduled to deliver at the National Center
for Child Health and Development in Tokyo, Japan. A total of 616 pregnant women,
from whom written informed consent will be obtained, will be allocated randomly
to an intervention group or a control group. Women in the control group will be
provided with anaemia prevention leaflets at 20 weeks' gestation and skin-care
leaflets at 30 weeks' gestation. Women in the intervention group will be provided
with the same leaflets and will also receive health advice from health
professionals to avoid constrictive clothing around the trunk. The primary
outcome will be a difference between these groups in the frequency of any one of
the following category variables: (1) cervical length <30 mm up to 28 weeks'
gestation, (2) hospital admission for threatened premature delivery, or (3)
premature delivery. Secondary outcomes will include QoL during pregnancy,
maternal state of health, and status of fetal development. ETHICS AND
DISSEMINATION: The Institutional Review Board and Ethics Committee at the
National Center for Child Health and Development, Japan, has approved this study.
Our findings will be widely disseminated through conference presentations and
peer-reviewed publications. TRIAL REGISTRATION NUMBER: UMIN000016853.
PMID- 26423852
TI - Providing immediate neonatal care and resuscitation at birth beside the mother:
clinicians' views, a qualitative study.
AB - OBJECTIVES: The aims of this study were to assess clinicians' views and
experiences of providing immediate neonatal care at birth beside the mother, and
of using a mobile trolley designed to facilitate this bedside care. DESIGN:
Qualitative interview study with semistructured interviews. RESULTS: The results
were analysed using thematic analysis. SETTING: A large UK maternity unit.
PARTICIPANTS: Clinicians (n=20) from a range of disciplines who were present when
the trolley was used to provide neonatal care at birth at the bedside. Five
clinicians provided/observed advanced resuscitation by the bedside. RESULTS: Five
themes were identified: (1) Parents' involvement, which included 'Contact and
involvement', 'Positive emotions for parents' and 'Staff communication'; (2)
Reservations about neonatal care at birth beside the mother, which included
'Impact on clinicians' and 'Impact on parents'; (3) Practical challenges in
providing neonatal care at the bedside, which included 'Cord length' and
'Caesarean section'; (4) Comparison of the trolley with usual resuscitation
equipment and (5) Training and integration of bedside care into clinical routine,
which included 'Teething problems' and 'Training'. CONCLUSIONS: Overall, most
clinicians were positive about providing immediate neonatal care at the maternal
bedside, particularly in terms of the clinicians' perceptions of the parents'
experience. Clinicians also perceived that their close proximity to parents
improved communication. However, there was some concern about performing more
intensive interventions in front of parents. Providing immediate neonatal care
and resuscitation at the bedside requires staff training and support.
PMID- 26423853
TI - Promoting professional behaviour change in healthcare: what interventions work,
and why? A theory-led overview of systematic reviews.
AB - OBJECTIVES: Translating research evidence into routine clinical practice is
notoriously difficult. Behavioural interventions are often used to change
practice, although their success is variable and the characteristics of more
successful interventions are unclear. We aimed to establish the characteristics
of successful behaviour change interventions in healthcare. DESIGN: We carried
out a systematic overview of systematic reviews on the effectiveness of behaviour
change interventions with a theory-led analysis using the constructs of
normalisation process theory (NPT). MEDLINE, CINAHL, PsychINFO and the Cochrane
Library were searched electronically from inception to July 2015. SETTING:
Primary and secondary care. PARTICIPANTS: Participants were any patients and
healthcare professionals in systematic reviews who met the inclusion criteria of
having examined the effectiveness of professional interventions in improving
professional practice and/or patient outcomes. INTERVENTIONS: Professional
interventions as defined by the Cochrane Effective Practice and Organisation of
Care Review Group. PRIMARY AND SECONDARY OUTCOME MEASURES: Success of each
intervention in changing practice or patient outcomes, and their mechanisms of
action. Reviews were coded as to the interventions included, how successful they
had been and which NPT constructs its component interventions covered. RESULTS:
Searches identified 4724 articles, 67 of which met the inclusion criteria.
Interventions fell into three main categories: persuasive; educational and
informational; and action and monitoring. Interventions focusing on action or
education (eg, Audit and Feedback, Reminders, Educational Outreach) acted on the
NPT constructs of Collective Action and Reflexive Monitoring, and reviews using
them tended to report more positive outcomes. CONCLUSIONS: This theory-led
analysis suggests that interventions which contribute to normative restructuring
of practice, modifying peer group norms and expectations (eg, educational
outreach) and relational restructuring, reinforcing modified peer group norms by
emphasising the expectations of an external reference group (eg, Reminders, Audit
and Feedback), offer the best chances of success. Combining such interventions is
most likely to change behaviour.
PMID- 26423854
TI - Clinical value of lncRNA MALAT1 as a prognostic marker in human cancer:
systematic review and meta-analysis.
AB - BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is
found to be overexpressed and associated with clinicopathological features in
patients with cancer. OBJECTIVES: To evaluate the clinical value of MALAT1 as a
prognostic marker in human cancers by a comprehensive meta-analysis of published
studies. DATA SOURCES: The data on the prognostic impact of MALAT1 in cancer were
collected from 11 September 2003 to 10 July 2015. SETTING AND PARTICIPANTS:
Fourteen eligible studies with a total of 1373 patients conducted in 3 countries
(9 in China, 3 in Japan and 2 in Germany) were matched to our inclusion criteria.
OUTCOME MEASURES: Pooled HRs with 95% CIs were calculated to estimate the
strength of the link between MALAT1 and clinical prognoses. The combined HRs
heterogeneity was tested using a chi(2)-based Cochran Q test and Higgins I(2)
statistic. Publication bias was evaluated using a funnel plot with Egger's bias
indicator test. RESULTS: A significant association between MALAT1 overexpression
and poor overall survival (OS) (HR=1.95; 95% CI 1.57 to 2.41) was observed.
Residence region (Germany and China), cancer type (respiratory, digestive or
other system disease), sample size and paper quality did not alter the predictive
value of MALAT1 on OS in investigated cancers. MALAT1 expression was an
independent prognostic marker for OS in patients with cancer using univariate and
multivariate analyses. Subgroup analysis showed that the elevated MALAT1 appeared
to be a powerful prognostic marker for patients with respiratory, digestive and
other system cancers. A similar effect was also seen in different regions.
Furthermore, the overexpression of MALAT1 was associated with disease-free,
recurrence-free and progression-free survivals. CONCLUSIONS: MALAT1 may
potentially be used as a new prognostic marker to predict poorer survival of
patients with cancer. More clinical studies on the different types of human
cancer not yet investigated need to be conducted.
PMID- 26423855
TI - Retrospective analysis of the quality of reports by author-suggested and non
author-suggested reviewers in journals operating on open or single-blind peer
review models.
AB - OBJECTIVES: To assess whether reports from reviewers recommended by authors show
a bias in quality and recommendation for editorial decision, compared with
reviewers suggested by other parties, and whether reviewer reports for journals
operating on open or single-blind peer review models differ with regard to report
quality and reviewer recommendations. DESIGN: Retrospective analysis of the
quality of reviewer reports using an established Review Quality Instrument, and
analysis of reviewer recommendations and author satisfaction surveys. SETTING:
BioMed Central biology and medical journals. BMC Infectious Diseases and BMC
Microbiology are similar in size, rejection rates, impact factors and editorial
processes, but the former uses open peer review while the latter uses single
blind peer review. The Journal of Inflammation has operated under both peer
review models. SAMPLE: Two hundred reviewer reports submitted to BMC Infectious
Diseases, 200 reviewer reports submitted to BMC Microbiology and 400 reviewer
reports submitted to the Journal of Inflammation. RESULTS: For each journal,
author-suggested reviewers provided reports of comparable quality to non-author
suggested reviewers, but were significantly more likely to recommend acceptance,
irrespective of the peer review model (p<0.0001 for BMC Infectious Diseases, BMC
Microbiology and the Journal of Inflammation). For BMC Infectious Diseases, the
overall quality of reviewer reports measured by the Review Quality Instrument was
5% higher than for BMC Microbiology (p=0.042). For the Journal of Inflammation,
the quality of reports was the same irrespective of the peer review model used.
CONCLUSIONS: Reviewers suggested by authors provide reports of comparable quality
to non-author-suggested reviewers, but are significantly more likely to recommend
acceptance. Open peer review reports for BMC Infectious Diseases were of higher
quality than single-blind reports for BMC Microbiology. There was no difference
in quality of peer review in the Journal of Inflammation under open peer review
compared with single blind.
PMID- 26423856
TI - Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE): a prospective
multicountry study.
AB - INTRODUCTION: Despite cooling, adverse outcomes are seen in up to half of the
surviving infants after neonatal encephalopathy. A number of novel adjunct drug
therapies with cooling have been shown to be highly neuroprotective in animal
studies, and are currently awaiting clinical translation. Rigorous evaluation of
these therapies in phase II trials using surrogate MR biomarkers may speed up
their bench to bedside translation. A recent systematic review of single-centre
studies has suggested that MR spectroscopy biomarkers offer the best promise;
however, the prognostic accuracy of these biomarkers in cooled encephalopathic
babies in a multicentre setting using different MR scan makers is not known.
METHODS AND ANALYSIS: The MR scanners (3 T; Philips, Siemens, GE) in all the
participating sites will be harmonised using phantom experiments and healthy
adult volunteers before the start of the study. We will then recruit 180
encephalopathic infants treated with whole body cooling from the participating
centres. MRI and spectroscopy will be performed within 2 weeks of birth.
Neurodevelopmental outcomes will be assessed at 18-24 months of age. Agreement
between MR cerebral biomarkers and neurodevelopmental outcome will be reported.
The sample size is calculated using the 'rule of 10', generally used to calculate
the sample size requirements for developing prognostic models. Considering 9
parameters, we require 9*10 adverse events, which suggest that a total sample
size of 180 is required. ETHICS AND DISSEMINATION: Human Research Ethics
Committee approvals have been received from Brent Research Ethics Committee
(London), and from Imperial College London (Sponsor). We will submit the results
of the study to relevant journals and offer national and international
presentations. TRIAL REGISTRATION NUMBER: Clinical Trials.gov Number:
NCT01309711.
PMID- 26423857
TI - German Cranial Reconstruction Registry (GCRR): protocol for a prospective,
multicentre, open registry.
AB - INTRODUCTION: Owing to increasing numbers of decompressive craniectomies in
patients with malignant middle cerebral artery infarction, cranioplastic surgery
becomes more relevant. However, the current literature mainly consists of
retrospective single-centre (evidence class III) studies. This leads to a wide
variability of technical approaches and clinical outcomes. To improve our
knowledge about the key elements of cranioplasty, which may help optimising
clinical treatment and long-term outcome, a prospective multicentre registry
across Germany, Austria and Switzerland will be established. METHODS: All
patients undergoing cranioplastic surgery in participating centres will be
invited to join the registry. Technical methods, materials, medical history,
adverse events and clinical outcome measures, including modified Rankin scale and
EQ-5D, will be assessed at several time points. Patients will be accessible to
inclusion either at initial decompressive surgery or when cranioplasty is
planned. Scheduled monitoring will be carried out at time of inclusion and
subsequently at time of discharge, if any readmission is necessary, and at follow
up presentation. Cosmetic results and patient satisfaction will also be assessed.
Collected data will be managed and statistically analysed by an independent
biometric institute. The primary endpoint will be mortality, need for operative
revision and neurological status at 3 months following cranioplasty. ETHICS AND
DISSEMINATION: Ethics approval was obtained at all participating centres. The
registry will provide reliable prospective evidence on surgical techniques, used
materials, adverse events and functional outcome, to optimise patient treatment.
We expect this study to give new insights in the treatment of skull defects and
to provide a basis for future evidence-based therapy regarding cranioplastic
surgery. TRIAL REGISTRATION NUMBER: This trial is indexed in the German Clinical
Trials Register (DRKS-ID: DRKS00007931). The Universal Trial Number (UTN) is
U1111-1168-7425.
PMID- 26423858
TI - Reporting, handling and assessing the risk of bias associated with missing
participant data in systematic reviews: a methodological survey.
AB - OBJECTIVES: To describe how systematic reviewers are reporting missing data for
dichotomous outcomes, handling them in the analysis and assessing the risk of
associated bias. METHODS: We searched MEDLINE and the Cochrane Database of
Systematic Reviews for systematic reviews of randomised trials published in 2010,
and reporting a meta-analysis of a dichotomous outcome. We randomly selected 98
Cochrane and 104 non-Cochrane systematic reviews. Teams of 2 reviewers selected
eligible studies and abstracted data independently and in duplicate using
standardised, piloted forms with accompanying instructions. We conducted
regression analyses to explore factors associated with using complete case
analysis and with judging the risk of bias associated with missing participant
data. RESULTS: Of Cochrane and non-Cochrane reviews, 47% and 7% (p<0.0001),
respectively, reported on the number of participants with missing data, and 41%
and 9% reported a plan for handling missing categorical data. The 2 most reported
approaches for handling missing data were complete case analysis (8.5%, out of
the 202 reviews) and assuming no participants with missing data had the event
(4%). The use of complete case analysis was associated only with Cochrane reviews
(relative to non-Cochrane: OR=7.25; 95% CI 1.58 to 33.3, p=0.01). 65% of reviews
assessed risk of bias associated with missing data; this was associated with
Cochrane reviews (relative to non-Cochrane: OR=6.63; 95% CI 2.50 to 17.57,
p=0.0001), and the use of the Grading of Recommendations Assessment, Development
and Evaluation (GRADE) methodology (OR=5.02; 95% CI 1.02 to 24.75, p=0.047).
CONCLUSIONS: Though Cochrane reviews are somewhat less problematic, most Cochrane
and non-Cochrane systematic reviews fail to adequately report and handle missing
data, potentially resulting in misleading judgements regarding risk of bias.
PMID- 26423859
TI - Increased urothelial paracellular transport promotes cystitis.
AB - Changes in the urothelial barrier are observed in patients with cystitis, but
whether this leads to inflammation or occurs in response to it is currently
unknown. To determine whether urothelial barrier dysfunction is sufficient to
promote cystitis, we employed in situ adenoviral transduction to selectively
overexpress the pore-forming tight junction-associated protein claudin-2 (CLDN
2). As expected, the expression of CLDN-2 in the umbrella cells increased the
permeability of the paracellular route toward ions, but not to large organic
molecules. In vivo studies of bladder function revealed higher intravesical basal
pressures, reduced compliance, and increased voiding frequency in rats transduced
with CLDN-2 vs. controls transduced with green fluorescent protein. While the
integrity of the urothelial barrier was preserved in the rats transduced with
CLDN-2, we found that the expression of this protein in the umbrella cells
initiated an inflammatory process in the urinary bladder characterized by edema
and the presence of a lymphocytic infiltrate. Taken together, these results are
consistent with the notion that urothelial barrier dysfunction may be sufficient
to trigger bladder inflammation and to alter bladder function.
PMID- 26423860
TI - Alternative channels for urea in the inner medulla of the rat kidney.
AB - The ascending thin limbs (ATLs) and lower descending thin limbs (DTLs) of Henle's
loop in the inner medulla of the rat are highly permeable to urea, and yet no
urea transporters have been identified in these sections. We hypothesized that
novel, yet-unidentified transporters in these tubule segments could explain the
high urea permeability. cDNAs encoding for Na(+)-glucose transporter 1a (SGLT1a),
Na(+)-glucose transporter 1 (NaGLT1), urea transporter (UT)-A2c, and UT-A2d were
isolated and cloned from the Munich-Wistar rat inner medulla. SGLT1a is a novel
NH2-terminal truncated variant of SGLT1. NaGLT1 is a Na(+)-dependent glucose
transporter primarily located in the proximal tubules and not previously
described in the thin limbs. UT-A2c and UT-A2d are novel variants of UT-A2. UT
A2c is truncated at the COOH terminus, and UT-A2d has one exon skipped. When rats
underwent water restriction for 72 h, mRNA levels of SGLT1a increased in ATLs,
NaGLT1 levels increased in both ATLs and DTLs, and UT-A2c increased in ATLs.
[(14)C]urea uptake assays performed on Xenopus oocytes heterologously expressing
these proteins revealed that despite having structural differences from their
full-length versions, SGLT1a, UT-A2c, and UT-A2d enhanced urea uptake. NaGLT1
also facilitated urea uptake. Uptakes were Na(+) independent and inhibitable by
phloretin and/or phloridzin. Our data indicate that there are several alternative
channels for urea in the rat inner medulla that could potentially contribute to
the high urea permeabilities in thin limb segments.
PMID- 26423862
TI - [Lessons Learned after 25 Years of Studies on the Physiological Roles of the
Peroxisome Proliferator-activated Receptor].
AB - The peroxisome proliferator-activated receptor (PPAR) was discovered a quarter of
a century ago. PPAR was soon recognized as a general transcriptional regulator of
lipid homeostasis, and several hypolipidemic and antidiabetic agents were shown
to be effective ligands for it. Since then, many attempts to develop more potent
drugs have been made worldwide, but most were unsuccessful due to serious side
effects. It appears that the PPAR boom has ended. This review summarizes the
short history of PPAR studies, including our own results, and discusses the
lessons learned from the rise and fall of studies in this field for next
generation basic studies and drug development research.
PMID- 26423861
TI - Bridging the translational divide: identical cognitive touchscreen testing in
mice and humans carrying mutations in a disease-relevant homologous gene.
AB - Development of effective therapies for brain disorders has been hampered by a
lack of translational cognitive testing methods. We present the first example of
using the identical touchscreen-based cognitive test to assess mice and humans
carrying disease-related genetic mutations. This new paradigm has significant
implications for improving how we measure and model cognitive dysfunction in
human disorders in animals, thus bridging the gap towards effective translation
to the clinic.
PMID- 26423863
TI - [Search for Structurally Unique Bioactive Natural Products].
AB - In our continuing search for structurally and biologically interesting
metabolites from marine organisms and plants, we investigated the constituents of
Okinawan marine sponges and Hypericum plants, resulting in the isolation of
several new and unique natural products. Their structures were elucidated on the
basis of spectroscopic analyses and chemical conversions. Novel bromopyrrole
alkaloids, nagelamides X-Z, were isolated from a sponge Agelas sp. Heteroaromatic
alkaloids, hyrtimomines A and B, were isolated from a sponge Hyrtios sp. together
with bisindole alkaloids, hyrtimomines C-E. An oxylipin with a trimeric
structure, manzamenone O, was obtained from a sponge Plakortis sp. Dimeric
eudesmane sesquiterpenes connected through various linker moieties, halichonadins
K-L, were isolated from a sponge Halichondria sp., and isomalabaricane
triterpenes, stelliferins J-N, were obtained from a sponge Rhabdastrella sp. The
investigation for the extracts of Hypericum plants gave new meroterpenes,
acylphloroglucinols, and xanthones. Biyoulactones A-E are meroterpenoids from the
roots of Hypericum chinense. Acylphloroglucinols, chipericumines A-D, and highly
prenylated xanthones, biyouxanthones A-D, were also isolated from the same
origin. Tricyclic meroterpenes, yezo'otogirins A-C, and liner meroterpenos,
yojironins A and B, were isolated from Hypericum yezoense and Hypericum
yojiroanum, respectively.
PMID- 26423864
TI - [Total Synthesis of Biologically Active Natural Products toward Elucidation of
the Mode of Action].
AB - Total synthesis of biologically active cyclodepsipeptide destruxin E using solid-
and solution-phase synthesis is described. The solid-phase synthesis of destruxin
E was initially investigated for the efficient synthesis of destruxin analogues.
Peptide elongation from polymer-supported beta-alanine was efficiently performed
using DIC/HOBt or PyBroP/DIEA, and subsequent cleavage from the polymer-support
under weakly acidic conditions furnished a cyclization precursor in moderate
yield. Macrolactonization of the cyclization precursor was smoothly performed
using 2-methyl-6-nitrobenzoic anhydride (MNBA)/4-(dimethylamino)pyridine N-oxide
(DMAPO) to afford macrolactone in moderate yield. Finally, formation of the
epoxide in the side chain via three steps provided destruxin E, and the
stereochemistry of the epoxide was determined to be S. Its diastereomer, epi
destruxin E, was also synthesized in the same manner used to synthesize the
natural product. The stereochemistry of the epoxide was critical for the V-ATPase
inhibition; natural product destruxin E exhibited 10-fold more potent V-ATPase
inhibition than epi-destruxin E. Next, the scalable synthesis of destruxin E for
in vivo study was also performed via solution-phase synthesis. The scalable
synthesis of a key component, (S)-HA-Pro-OH, was achieved using osmium-catalyzed
diastereoselective dihydroxylation with (DHQD)2PHAL as a chiral ligand; peptide
synthesis using Cbz-protected amino acid derivatives furnished the cyclization
precursor on a gram-scale. Macrolactonization smoothly provided the macrolactone
without forming a dimerized product, even at 6 mM, and the synthesis of destruxin
E was achieved via three steps on a gram scale in high purity (>98%).
PMID- 26423865
TI - [Discovery of Novel Biologically Active Compounds of Natural Origin, with a Focus
on Anti-tumor Activity].
AB - Numerous clinically valuable medicines, including anticancer drugs, have been
developed from biologically active natural compounds and their structurally
related derivatives. This review discusses novel natural compounds with promising
biological activities and those with novel chemical structures. Glaziovianin A,
an isoflavone isolated from the leaves of Ateleia glazioviana (Legminosae),
inhibited cell cycle progression at the M-phase with an abnormal spindle
structure. AU-1 and YG-1, 5beta-steroidal glycosides isolated from the whole
plants of Agave utahensis and the underground parts of Yucca glauca (Agavaceae),
induced apoptosis of HL-60 cells via caspase-3 activation. Lycolicidinol, an
alkaloid isolated from the bulbs of Lycoris albiflora (Amaryllidaceae), induced
transient autophagy and morphological changes in mitochondria in the early stage
of the apoptotic cell death process in HSC-2 cells. Taccasterosides isolated from
the rhizomes of Tacca chantrieri (Taccaceae) and stryphnosides isolated from the
pericarps of Stryphnodendron fissuratum (Legminosae) are steroidal and triterpene
glycosides with unique chemical structures having novel sugar sequences.
PMID- 26423866
TI - [Effects of Xenobiotics on Drug Pharmacokinetics and Safety].
AB - The use of nanotechnology has increased over the past 10 years, and various
nanomaterials with a wide range of applications have been developed. Carbon
nanotubes (CNTs), which are cylindrical molecules consisting of hexagonally
arranged carbon atoms, are nanomaterials with high utility. Recently,
applications of single-walled CNT (SWCNT) in the medical field for drug-delivery
and as gene-delivery agents have been proposed. Due to its structural
characteristics and physicochemical properties, the inhalation of SWCNT could be
considered as one route for targeted drug delivery into the lungs. Therefore, it
is necessary to investigate the effects of SWCNT on the physiological state and
response of the cells upon delivery into the lung. We clarified the different
response of two carcinoma cell lines to SWCNT exposure, and determined these
differences may be due to different cell functions. Furthermore, SWCNT exposure
resulted in a global downregulation of stress-responsive genes in normal human
bronchial epithelial cells, thereby indicating that the factors involved in the
stress responses were not activated by SWCNT. We then tried to ascertain the
possible effect of SWCNT on the fate of drugs delivered with SWCNT. Exposure to
SWCNT down-regulated the mRNA expression and enzymatic activity of CYP1A1 and
CYP1B1 by preventing the binding of activated aryl hydrocarbon receptors to the
enhancer region of these genes. This review provides basic information for the
prediction of human responses to SWCNT exposure by inhalation, and in its use as
a drug delivery carrier.
PMID- 26423867
TI - [Optimization of Immunosuppression and the Prevention of Fungal Infection in
Autoimmune Diseases].
AB - Mycophenolate mofetil (MMF) has recently been reported to be effective in the
treatment of systemic lupus erythematosus (SLE). The therapeutic range of
mycophenolic acid (MPA) and its 7-O-glucuronide (MPAG), and factors affecting
their pharmacokinetics, remain to be clarified. The influence of the
pharmacokinetics of MPA and MPAG on the activity of inosine 5'-monophosphate
dehydrogenase (IMPDH), a target of the MPA, also remains to be revealed. The
pharmacokinetic variability of hydroxy-itraconazole (OH-ITZ), an active
metabolite of itraconazole frequently co-administered with immunosuppressants in
immunocompromised patients, is not fully known. The aim of this study was to
establish the optimal dosage and administration of immunosuppressants and
antifungal agents. MMF improved clinical laboratory markers and reduced
prednisolone dosage in 31 SLE patients, with a pre-dose plasma concentration of
MPA and MPAG in the interquartile ranges of 0.94-2.96 and 18.6-53.7 MUg/mL,
respectively. Renal function and co-administered metal influenced the
pharmacokinetics of MPA and MPAG in 31 SLE patients in the remission maintenance
phase. IMPDH activity was induced in 29 SLE patients receiving the MMF therapy.
This induction was dependent on the plasma concentration of MPAG, but not MPA. In
addition, IMPDH activity was negatively correlated with complement fraction C3.
MPA exposure and disease activity in SLE patients may determine IMPDH activity.
The pharmacokinetic variability of OH-ITZ was associated with saturated
metabolism to keto-itraconazole, serum concentration of albumin, and renal
function in 46 immunocompromised patients. Prevention of fungal infections and
drug-drug interactions in immunocompromised patients can be obtained by
considering these identified confounding factors.
PMID- 26423868
TI - [Efficient Pharmaceutical Formulation Designs and Their Development Using
Mathematical and Statistical Analysis].
AB - With the aim of directly predicting the functionality and mechanism of
pharmaceutical excipients, we investigated an analysis method based on available
surface area (S(t)), which is the surface area of a drug in direct contact with
the external solvent during dissolution. First, to study the effect of lubricant
concentration on the dissolution rate of acetaminophen (APAP), the dissolution
behaviors as well as the change over time in S(t) of APAP tablets were examined.
In the dissolution tests, a retarded dissolution of APAP was not observed with
new lubricant triglycerin full behenate (TR-FB), whereas magnesium stearate (Mg
St) retarded the dissolution. The S(t) profiles for APAP with Mg-St at>0.5%
showed downward curvature indicating a gradual decrease in surface area over
time. Conversely, with TR-FB, even when its concentration was increased, the S(t)
profile for APAP had a maximum value. The differences between Mg-St and TR-FB
could be explained by the differences in extensibility deriving from their
morphology. Next, we evaluated the effect of disintegtant concentration using
five disintegrants. When disintegrant was added to ethenzamide tablet
formulation, an increase in the dissolution rate and S(t) dependent on
disintegrant concentration was observed, according to the type of disintegrant.
It was found that the water absorption ability of disintegrants had strong
correlations with the parameters of S(t). Taken together, this study demonstrates
that analysis of S(t) can directly provide useful information, especially about
the functionality of pharmaceutical excipients.
PMID- 26423869
TI - [Carrier-mediated Transport of Cationic Drugs across the Blood-Tissue Barrier].
AB - Studies of neurological dysfunction have revealed the neuroprotective effect of
several cationic drugs, suggesting their usefulness in the treatment of
neurological diseases. In the brain and retina, blood-tissue barriers such as
blood-brain barrier (BBB) and blood-retinal barrier (BRB) are formed to restrict
nonspecific solute transport between the circulating blood and neural tissues.
Therefore study of cationic drug transport at these barriers is essential to
achieve systemic delivery of neuroprotective agents into the neural tissues. In
the retina, severe diseases such as diabetic retinopathy and macular degeneration
can cause neurological dysfunction that dramatically affects patients' QOL. The
BRB is formed by retinal capillary endothelial cells (inner BRB) and retinal
pigment epithelial cells (outer BRB). Blood-to-retina transport of cationic drugs
was investigated at the inner BRB, which is known to nourish two thirds of the
retina. Blood-to-retinal transport of verapamil suggested that the barrier
function of the BRB differs from that of the BBB. Moreover, carrier-mediated
transport of verapamil and pyrilamine revealed the involvement of novel organic
cation transporters at the inner BRB. The identified transport systems for
cationic drugs are sensitive to several cationic neuroprotective and anti
angiogenic agents such as clonidine and propranolol, and the involvement of novel
transporters was also suggested in their blood-to-retina transport across the
inner BRB.
PMID- 26423870
TI - [Establishment of a Method of Hepatocyte Differentiation from Human Pluripotent
Stem Cells for Innovative Drug Development].
AB - Hepatocyte-like cells differentiated from human pluripotent stem cells (such as
human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells) are
expected to be utilized in drug screening. However, the hepatocyte
differentiation efficiency and hepatic functions of hepatocyte-like cells were
not sufficient to perform ES/iPS cell-based drug discovery. Therefore, we decided
to improve the method of hepatocyte differentiation from human ES/iPS cells. To
enhance this hepatocyte differentiation efficiency, hepatocyte-related
transcription factors, such as forkhead box protein A2 (FOXA2) and hepatocyte
nuclear factor 1 alpha (HNF1alpha), were overexpressed during the hepatocyte
differentiation process. In addition, to enhance the functions of hepatocyte-like
cells, these cells were cultured in three dimensional (3D) conditions using a
Nanopillar plate. By FOXA2 and HNF1alpha overexpression, human ES/iPS cells could
efficiently (more than 80%) differentiate into albumin-positive hepatocyte-like
cells. Various hepatic functions, including albumin secretion and drug metabolism
capacities, of the hepatocyte-like cells were significantly enhanced by
performing 3D cell culture. These results suggest that the method of hepatocyte
differentiation could be improved by using gene transfer and 3D cell culture
technologies. We believe that these new hepatocyte-like cells would be useful
tools in drug development.
PMID- 26423871
TI - [Search of Neurotrophin-mimic Natural Products for Prevention and Treatment of
Neurodegenerative Disease].
AB - As part of our continuing studies on neurotrophin-mimic active compounds in
natural products, we investigated the chemical constituents of the pericarps of
Illicium jiadifengpi and the roots of Indonesian ginger Zingiber purpureum,
resulting in the isolation of new seco-prezizaane-type sesquiterpenoid 1 and
phenylbutenoid dimer 3-4 and two new curcuminoids 5-6. The MeOH extract of I.
jiadifengpi was fractionated, leading to the isolation of compound 1. Compound 1
significantly enhanced neurite outgrowth in primary cell cultures of fetal rat
cortical neurons. It is noteworthy that compound 1 has potential significantly to
promote differentiation of multipotent neural stem cell line (MEB5 cells) into
neurons. Additionally, we investigated the MeOH extract of the root of Bangle (Z.
purpureum) that exhibited neuritogenesis activity in PC12 cells at 25 MUg/mL,
resulting in the isolation of neurotrophic phenylbutenoid dimers 3-4 and new
compounds 5-6. Compounds 3 and 4 were found not only significantly to induce
neurite sprouting of PC12 cells but also to increase the neurite length and
number of neurites in primary cultured rat cortical neurons, and also showed
protective activity against cell death caused by deprivation of serum.
Furthermore, chronic treatment with these compounds enhanced hippocampal
neurogenesis in dementia model olfactory bulbectomized (OBX) mice. Compounds 5
and 6 had significant NGF-potentiating effects on PC12 cells whereas compound 5
enhanced prevention of amyloid beta (Abeta) 42 aggregation.
PMID- 26423872
TI - [Effects of Bioactive Substances from Citrus on the Central Nervous System and
Utilization as Food Material].
AB - We have recently shown that 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) and
auraptene (AUR) have neuroprotective effects on the central nervous system. HMF,
a citrus flavonoid, altered NMDA-type glutamate receptor antagonist MK-801
induced memory dysfunction and schizophrenia-positive symptom-like behavior. HMF
also showed a protective effect against ischemia-induced short-term memory
dysfunction. In the ischemic brain, HMF induced the following protective effects
against brain dysfunction: 1) rescue of neuronal cell death in the hippocampus;
2) increased production of brain-derived neurotrophic factor; 3) stimulation of
neurogenesis in the dentate gyrus subgranular zone; 4) activation of the
autophosphorylation of calcium-calmodulin-dependent protein kinase II; and 5)
suppression of microglial activation. On the other hand, AUR, a citrus coumarin,
ameliorated lipopolysaccharide-induced inflammation in the brain as shown by
inhibition of microglial activation and inhibition of cyclooxygenase (COX)-2
expression in the hippocampus. AUR also showed antiinflammatory effects on the
ischemic brain by inhibiting microglial activation, COX-2 expression, and
neuronal cell death in the hippocampus. The peel of kawachibankan (Citrus
kawachiensis), a noted citrus product of Ehime prefecture, Japan, contains AUR,
HMF, naringin, and narirutin. The dried powder of both the peel and juice had
antiinflammatory effects in the mouse hippocampus, suggesting that citrus
compounds may be beneficial as neuroprotective agents in the treatment of
neurological disorders.
PMID- 26423874
TI - [Effect of Water Intake on Allergy-like Events Associated with Non-ionic Iodine
Contrast Agents].
AB - The use of iodine contrast agents occasionally causes serious allergic symptoms
including anaphylaxis. At Kyoto University Hospital to prevent nephropathy we
began recommending water intake before and after administration of iodine
contrast agents in September 2012. In the present study we investigated the
effect of water intake on the incidence of allergy-like events after the use of
non-ionic iodine contrast agents. We extracted the occurrence of allergy-like
events from the incident report system in our hospital from January 2011 to
September 2014, and classified these events into the following 3 grades: 1+
(follow-up); 2+ (medication treatment); and 3+ (hospitalization). The allergy
like incidence rate was calculated for subsequent evaluation according to season
and water intake. Allergy-like events significantly decreased from 0.49% before
the recommendation of water intake to 0.26% at 1 year and 0.20% at 2 years after
implementing the recommendation. The incidence of allergy-like events was
significantly higher in summer than in winter before water intake was
recommended. After implementing the recommendation, the value for summer
significantly decreased to an incidence similar to that of winter. Respiratory
and gastrointestinal allergy-like symptoms were dramatically decreased after
implementing the recommendation. Water intake may be useful for preventing
allergy-like events associated with non-ionic iodine contrast agents, especially
during the summer.
PMID- 26423873
TI - [The Xanthine Oxidase Inhibitory Activity and Hypouricemic Effects of Crude Drugs
Obtained from the Silkworm in Mice].
AB - This study evaluated the effects of crude drugs obtained from the silkworm in
mice with oxonic acid-induced hyperuricemia using xanthine oxidase inhibitory
activity and plasma uric acid levels. The plasma uric acid level was analyzed
using an improved HPLC with UV detection (HPLC-UV) method, which enabled high
sensitivity analysis of a microliter of plasma. Using this method, we evaluated
natural products administered orally to the hypouricemic mice. The plasma uric
acid level of mice administered a water-soluble extract from silkworm larvae with
botrytis (used in traditional Chinese medicine to reduce wind, lower blood
pressure, and change platelet coagulation) was significantly lower than in the
control group 1, 2, and 3 h after treatment. In addition, water soluble extracts
from a fungus (NBRC 31161) metabolite and silkworm pupae and larvae reduced the
plasma uric acid levels in mice compared with the control group.
PMID- 26423875
TI - [Aryl Hydrocarbon Receptor Ligand Activity of Extracts from 62 Herbal Medicines
and Effect on Cytochrome P450 Activity].
AB - Aryl hydrocarbon receptor (AhR) ligand activity of the extracts of 62 herbal
medicines was examined using yeast reporter assay. Fifty-eight herbal extracts
exhibited AhR ligand activity. The highest activity was observed with Ogon
(Scutellariae Radix), followed by Oren (Coptidis Rhizoma), Kujin (Sophorae Radix)
and Shoma (Cimicifiigae Rhizoma). When these extracts were treated with
hesperinase, a hydrolase for sugar conjugates, the aglycones showed higher
activity than the parent extracts. Among the constituents of Ogon extract,
baicalein and wogonin showed AhR ligand activity, while the sugar conjugate of
baicalein, baicalin, was inactive. Among the flavonoid components of these herbal
medicines, flavone and chrysin exhibited high ligand activity for AhR.
Ethoxyresorufin O-dealkylase (EROD) activity due to CYP1A1 in HepG2 cells was
enhanced by the addition of baicalein. Baicalein also decreased the 3
methylcholanthrene-induced increase of EROD activity, but this effect was not
statistically significant. When wogonin or baicalein was orally administered at
the dose of 100 mg/kg to mice, EROD activity in liver was only slightly changed.
Furthermore, when Ogon extract was co-administered with 3-methylcholanthrene, the
EROD and methoxyresorufin O-dealkylase activities were not significantly changed.
These results indicate that many herbal extracts have AhR ligand activity, and
their inducing effect on CYP1A1/2 can be evaluated in HepG2 cells.
PMID- 26423876
TI - [Editorial].
PMID- 26423877
TI - [Suicide - ethical and juridical aspects].
AB - This paper discusses the phenomenon of suicidality with regard to patient
autonomy on the one hand and the obligation of medical professionals to provide
support and treatment on the other hand. The continuation of a broad debate on
these issues within the whole of society is mandatory also in the future. Suicide
and assisted suicide are topics with high relevance for medicine in general and
for psychiatry in particular. They can, however, not be handled by medical
specialists alone.
PMID- 26423878
TI - [Suicide - background, epidemiology, risk factors].
AB - Suicide research, in particular epidemiology, comprises a huge amount of data.
However, the theoretical understanding clearly lags behind the empirical
knowledge. Suicide, suicide attempts and other suicidal behaviors are more
heterogeneous than most explanatory approaches would assume. The most important
recent contributions to a better understanding have come from selected
epidemiological findings and, interestingly, prevention. This article provides an
overview of epidemiological findings, the most relevant risk factors and
conclusions related to successful preventive efforts.
PMID- 26423879
TI - [Suicidality in mental illness - prevention and therapy].
AB - The great majority of suicides and suicide attempts are related to mental
illness. Special risk has been attributed to depression, psychosis, substance
use, personality, and trauma-related disorders. Many affected persons seek
medical attention prior to taking action. Primary care therefor plays an
outstanding role in suicide prevention. Doctors should pay attention to potential
risk constellations and actively address the issue. This paper presents possibly
helpful models and instruments for everyday use. Most importantly, however,
professionals' empathy and time are required as well as appropriate decisions
concerning a referral to a psychiatrist or psychiatric inpatient treatment.
PMID- 26423880
TI - [Prevention and interventions for suicidal youth considerations for health
professionionals in Switzerland].
AB - Adolescence is associated with a dramatic surge in suicide rate. While worldwide
age-adjusted suicides rate per 100'000 in under 14-year olds are relatively low
around 0.6, a dramatic increase to 7.4 can be observed in 15 - 19 year olds with
suicide being one of the three leading causes of mortality in most countries in
this age group. From 2000 to 2013 the Swiss annual average of completed suicides
in 15 - 19 year olds was 33.1 (minimum 24; maximum 47). This corresponds to an
average age-specific death rate of 7.6, which is slightly above the global mean.
Suicide prevention and treatment of suicidality in adolescents is a complex
underpinning. Subjectively experienced feelings of insufficiency, hopelessness
and the feeling of worthlessness combined with concrete suicidal ideations and
the capacity to act out are important indicators for assessing suicidal risk.
Suicide attempts as the strongest risk factor for suicide should always be taken
seriously, even if they occur in the context of situational crisis. Narcissistic
personality traits or increased impulsivity are further indicators of risk. The
early detection and effective treatment of mental disorders such as depression,
anxiety disorders, bipolar-affective disorders or psychotic disorders provide a
great opportunity to reduce the frequency of suicide attempts and suicide.
Particular caution is required when co-morbid addictions are present. The
maintenance or establishment of sustainable relationships with significant others
is considered a key protecting factor. Increasing withdrawal from significant
others is an important warning sign and needs urgent involvement of experts. In
acute suicidality, the admission to a psychiatric hospital must be considered, if
necessary against the will of affected adolescent and their relatives.
Personality-related recurrent suicidal behavior requires specific treatment
approaches taking into account the prevention of iatrogenic worsening of suicidal
patterns.
PMID- 26423881
TI - [Suicide in the elderly - risk factors and prevention].
AB - Suicide rates are highest among the elderly in Switzerland. The estimated number
of unreported cases is particularly high in this age group. The risk factors are
multidimensional, including depression and social isolation. The detection and
management of the controllable risk factors, foremost depression, is of
particular importance for suicide prevention. Old age depression often shows an
atypical presentation, is misinterpreted as a normal process of aging and is not
adequately treated.
PMID- 26423882
TI - [Suicidality at the general hospital - perspective of consultation and liaison
psychiatry].
AB - Suicidality is a common problem in the general hospital. Patients with comorbid
psychiatric disorders or during a psychosocial crisis can develop suicidal
ideation during their stay at the general hospital, especially if they suffer
from chronic disease. Some somatic disorders, such as cancer, epilepsy, chronic
obstructive pulmonary disease, asthma, stroke and chronic pain conditions are
associated with an increased risk of suicide. The fact that (1) a major part of
patients are treated in the emergency room (ER) after a suicide attempt and (2) a
suicide attempt is the strongest predictor for later completed suicide emphasizes
the importance of expertise in dealing with suicidal patients in the ER. In order
to improve prevention of suicides and suicide attempts within the general
hospital and after discharge it is important to educate staff concerning
suicidality and enhance detection of suicidal patients. A consultation and
liaison psychiatrist should always be involved when there are suicidal patients
on wards and in the ER. Assessment of suicidal patients has always to include
clear recommendations concerning patient safety and treatment of the underlying
condition as well as specific approaches in dealing with suicidal thoughts.
Safety measures can include close monitoring, constant observation, restriction
to means of suicide, referral to a psychiatric clinic and treatment with
sedatives, generally benzodiazepines. Psychiatric disorders are ideally treated
according to guidelines and clear recommendations should be given concerning
treatment after discharge. Specific psychotherapy for suicidal behaviour possibly
reduces the risk of future suicides. A special situation is created by assisted
suicides which attribute to suicides in the elderly with a recent increase in the
Swiss population. In some cases, undiagnosed depression may contribute to the
decision making process, hence, underlining the importance of improved detection
and treatment of depression in the elderly.
PMID- 26423883
TI - ["I want to die" - dealing with suicidal wishes in primary palliative care].
AB - Different attitudes towards, and ideas about the end of life, represent an often
experienced challenge in palliative care provided by family doctors. If values
diverge too strongly, considerable strain can originate from it for the health
care professionals, in particular if it is about assisted suicide. How do family
doctors experience the incompatibility between patients' wishes and personal
values? How do they succeed to bridge value divergences? Based on group
discussions with family doctors in Switzerland the contribution focusses on these
questions and identifies different strategies of family doctors. The results
indicate that in particular 'convergence of perspectives' with patients can
reduce the strain for family doctors and can at the same time guarantee high
quality of care.
PMID- 26423884
TI - [Suicide and suicidality in immigrant populations - transcultural aspects].
AB - To live as an immigrant in a foreign environment trying to restart his/her life
is a major challenge for an individual and requires outstanding coping
capacities. Some categories of immigrants suffer therefore from significant
psychological stress and are at elevated risk for attempted or completed suicide:
e. g. asylum seekers, second generation immigrants, uprooted refugees. In order
to evaluate correctly the suicide risk and to offer effective treatment, a
comprehensive assessment of the patient's history of migration is required. Only
through a careful exploration of a patient's history and actual reality of life
an effective approach is possible. The involvement of trained interpreters is
essential if clinician and patient have no common language. Makeshifts like
family members or friends as interpreters are not qualified and must be avoided.
To approach the patient in an open minded, not judgmental, empathetic attitude is
the key, and even culturally very different patients will be contactable.
PMID- 26423885
TI - [Managment of the suicidal patient in the out-patient practice].
AB - Appropriate handling of suicidal tendencies is for certain one of the most
important duties within ambulant treatment. As various examples show, occurrence
of a suicidal tendency can be chronical as well as acute. Well-known risk factors
including current psychopathology and psychodynamics help to identify and assess
a suicidal tendency and to take necessary therapeutic options. Some of these can
be applied in general, others have to be tailored specifically with respect to
the mental disorder in question. Suicide often occurs in an interpersonal
context. This fact underlines on one hand the importance and the therapeutic
potential of the relationship between the patient and the therapist, on the other
hand it results in many cases in a highly stressful situation for the therapist.
Significant attention has to be paid to counter transference and its control.
Development of an emergency plan and challenges of a "non-suicidal-contract" are
discussed. We recommend an agreement with the patient to contact the therapist in
case of not feeling able to control his/her own actions. This agreement includes
our guarantee of permanent reachability.
PMID- 26423886
TI - Berry intake changes hepatic gene expression and DNA methylation patterns
associated with high-fat diet.
AB - The liver is a critical organ for regulation of energy homeostasis and fatty
liver disease is closely associated with obesity and insulin resistance. We have
previously found that lingonberries, blackcurrants and bilberries prevent,
whereas acai berries exacerbate, the development of hepatic steatosis and obesity
in the high-fat (HF)-fed C57BL/6J mouse model. In this follow-up study, we
investigated the mechanisms behind these effects. Genome-wide hepatic gene
expression profiling indicates that the protective effects of lingonberries and
bilberries are accounted for by several-fold downregulation of genes involved in
acute-phase and inflammatory pathways (e.g. Saa1, Cxcl1, Lcn2). In contrast, acai
fed mice exhibit marked upregulation of genes associated with steatosis (e.g.
Cfd, Cidea, Crat) and lipid and cholesterol biosynthesis, which is in line with
the exacerbation of HF-induced hepatic steatosis in these mice. In silico
transcription factor analysis together with immunoblot analysis identified NF
kappaB, STAT3 and mTOR as upstream regulators involved in mediating the observed
transcriptional effects. To gain further insight into mechanisms involved in the
gene expression changes, the HELP-tagging assay was used to identify
differentially methylated CpG sites. Compared to the HF control group,
lingonberries induced genome-wide hypermethylation and specific hypermethylation
of Ncor2, encoding the corepressor NCoR/SMRT implicated in the regulation of
pathways of metabolic homeostasis and inflammation. We conclude that the
beneficial metabolic effects of lingonberries and bilberries are associated with
downregulation of inflammatory pathways, whereas for blackcurrants, exerting
similar metabolic effects, different mechanisms of action appear to dominate. NF
kappaB, STAT3 and mTOR are potential targets of the health-promoting effects of
berries.
PMID- 26423887
TI - Table grape consumption reduces adiposity and markers of hepatic lipogenesis and
alters gut microbiota in butter fat-fed mice.
AB - Our objective was to determine if consuming table grapes reduces adiposity and
its metabolic consequences and alters gut microbiota in mice fed a high-fat (HF),
butter-rich diet. C57BL/6J mice were fed a low-fat (LF) diet or HF diet with 3%
or 5% grapes for 11weeks. Total body and inguinal fat were moderately but
significantly reduced in mice fed both levels of grapes compared to their
controls. Mice fed 5% grapes had lower liver weights and triglyceride levels and
decreased expression of glycerol-3-phosphate acyltransferase (Gpat1) compared to
the 5% controls. Mice fed 3% grapes had lower hepatic mRNA levels of peroxisome
proliferator-activated receptor gamma 2, sterol-CoA desaturase 1, fatty-acid
binding protein 4 and Gpat1 compared to the 3% controls. Although grape feeding
had only a minor impact on markers of inflammation or lipogenesis in adipose
tissue or intestine, 3% of grapes decreased the intestinal abundance of
sulfidogenic Desulfobacter spp. and the Bilophila wadsworthia-specific
dissimilatory sulfite reductase gene and tended to increase the abundance of the
beneficial bacterium Akkermansia muciniphila compared to controls. In addition,
Bifidobacterium, Lactobacillus, Allobaculum and several other genera correlated
negatively with adiposity. Allobaculum in particular was increased in the LF and
3% grapes groups compared to the HF-fed controls. Notably, grape feeding
attenuated the HF-induced impairment in epithelial localization of the intestinal
tight junction protein zonula occludens. Collectively, these data indicate that
some of the adverse health consequences of consuming an HF diet rich in saturated
fat can be attenuated by table grape consumption.
PMID- 26423889
TI - IgA-Dominant Postinfectious Glomerulonephritis.
PMID- 26423888
TI - Precision of the Kalon Herpes Simplex Virus Type 2 IgG ELISA: an international
inter-laboratory assessment.
AB - BACKGROUND: The commercial Kalon HSV-2 IgG ELISA is currently recommended for
research use in sub-Saharan Africa because of its superior accuracy compared to
other serologic assays. However, there are no data on key precision parameters of
Kalon such as inter-operator variation, repeatability, and reproducibility, thus
contributing to a barrier for its acceptance and use in clinical trials in sub
Saharan Africa. We evaluated the analytical and field precision of the Kalon HSV
2 IgG ELISA. METHODS: A total of 600 HIV-infected and uninfected serum samples
from South Africa and Zambia, previously tested by the gold standard University
of Washington HSV western blot (UW-WB), were tested using Kalon by two
technologists in an United States reference laboratory. Aliquots of 183 samples
were retested using Kalon by an on-site technologist in a South African
laboratory and a Zambian laboratory. RESULTS: Intra-assay variation was below 10
%. Intra-assay, intra-laboratory, and inter-laboratory correlation and agreement
were significantly high (p < 0.01). In comparison to the UW-WB, accurate
performance of Kalon was reproducible by each operator and laboratory. Receiver
operating characteristic curve analysis indicated high selectivity of Kalon in
the overall study population (area under the curve = 0.95, 95%CI = 0.92-0.97).
DISCUSSION: Kalon is a robust assay with high precision and reproducibility.
Accordingly, operator errorlikely does not contribute to the variability observed
in Kalon's specificity throughout sera from sub-Saharan Africa. CONCLUSIONS: In
populations with optimal diagnostic accuracy, Kalon is a reliable stand-alone
method for on-site HSV-2 IgG antibody detection.
PMID- 26423890
TI - A Comparison of Bladder Catheterization and Suprapubic Aspiration Methods for
Urine Sample Collection From Infants With a Suspected Urinary Tract Infection.
AB - This study compares 2 sampling methods for urine cultures in young infants. We
analyzed data on urine samples obtained from 83 infants using 2 sources of urine:
suprapubic bladder aspiration (SPA) and bladder catheterization. All specimens
were subjected to both urinalysis and culture, and the results compared. Eighty
three infants with positive urine culture results obtained by bladder
catheterization were subjected to SPA. Of these, only 24 (28.9%) and 20 (24%)
yielded positive urine culture and abnormal urinalysis data, respectively.
Samples obtained via catheterization had a high false-positive rate (71.1%). The
sensitivity and specificity of urinalysis were 66.7% (95% CI, 44.68% to 84.33%)
and 93.22% (95% CI, 83.53% to 98.08%), respectively. In infants younger than 12
months, SPA is the best method to avoid bacterial contamination, showing better
results than transurethral catheterization.
PMID- 26423891
TI - An 8-Year-Old Boy With Abdominal Distension and Constipation.
PMID- 26423892
TI - Effect of end-stage renal disease on long-term survival after a first-ever
mechanical ventilation: a population-based study.
AB - INTRODUCTION: Patients with end-stage renal disease (ESRD(Pos)) usually have
multiple comorbidities and are predisposed to acute organ failure and in-hospital
mortality. We assessed the effect of ESRD on the poorly understood long-term
mortality risk after a first-ever mechanical ventilation (1-MV) for acute
respiratory failure. METHODS: The data source was Taiwan's National Health
Insurance (NHI) Research Database. All patients given a 1-MV between 1999 and
2008 from one million randomly selected NHI beneficiaries were identified (n =
38,659). Patients with or without ESRD (ESRD(Neg)) after a 1-MV between 1999 and
2008 were retrospectively compared and followed from the index admission date to
death or the end of 2011. ESRD(Pos) patients (n = 1185; mean age: 65.9 years;
men: 51.5 %) were individually matched to ESRD(Neg) patients (ratio: 1:8) using a
propensity score method. The primary outcome was death after a 1-MV. The effect
of ESRD on the risk of death after MV was assessed. A Cox proportional hazard
regression model was used to assess how ESRD affected the mortality risk after a
1-MV. RESULTS: The baseline characteristics of the two cohorts were balanced, but
the incidence of mortality was higher in ESRD(Pos) patients than in ESRD(Neg)
patients (342.30 versus 179.67 per 1000 person-years; P <0.001; covariate
adjusted hazard ratio: 1.43; 95 % confidence interval: 1.31-1.51). For patients
who survived until discharge, ESRD was not associated with long-term (>4 years)
mortality. CONCLUSIONS: ESRD increased the mortality risk after a 1-MV, but long
term survival seemed similar.
PMID- 26423893
TI - Piezoresistive effects in controllable defective HFTCVD graphene-based flexible
pressure sensor.
AB - In this work, the piezoresistive effects of defective graphene used on a flexible
pressure sensor are demonstrated. The graphene used was deposited at substrate
temperatures of 750, 850 and 1000 degrees C using the hot-filament thermal
chemical vapor deposition method in which the resultant graphene had different
defect densities. Incorporation of the graphene as the sensing materials in
sensor device showed that a linear variation in the resistance change with the
applied gas pressure was obtained in the range of 0 to 50 kPa. The deposition
temperature of the graphene deposited on copper foil using this technique was
shown to be capable of tuning the sensitivity of the flexible graphene-based
pressure sensor. We found that the sensor performance is strongly dominated by
the defect density in the graphene, where graphene with the highest defect
density deposited at 750 degrees C exhibited an almost four-fold sensitivity as
compared to that deposited at 1000 degrees C. This effect is believed to have
been contributed by the scattering of charge carriers in the graphene networks
through various forms such as from the defects in the graphene lattice itself,
tunneling between graphene islands, and tunneling between defect-like structures.
PMID- 26423894
TI - Childhood trauma and parental style: Relationship with markers of inflammation,
oxidative stress, and aggression in healthy and personality disordered subjects.
AB - Recent studies suggest that early life trauma is associated with elevations in
circulating markers of inflammation in human subjects. History of aggression as a
behavior, or aggression as a personality trait, is also associated with
elevations of these inflammatory markers. Since early life trauma is associated
with the development and maintenance of aggression in later life we examined the
relationship of early life adversity, plasma inflammation markers (IL-6 and CRP)
and oxidative stress markers (8-OH-DG and 8-ISO), and aggression in adult
subjects with (n=79) and without (n=55) personality disorder. We used a series of
mediated and moderated path models to test whether the effects of early adversity
on later aggression may be mediated through markers of inflammation. Childhood
abuse and parental control were associated with basal IL-6 and CRP
concentrations. Path modeling suggested that childhood abuse was associated with
aggression indirectly through CRP while parental control influenced aggression
indirectly through IL-6 and CRP. Furthermore, these effects were independent of
the effect of current depression. The results suggest that disruption of
inflammatory processes represent one pathway by which early adversity influences
aggression.
PMID- 26423895
TI - Has variation in length of stay in acute hospitals decreased? Analysing trends in
the variation in LOS between and within Dutch hospitals.
AB - BACKGROUND: We aimed to get better insight into the development of the variation
in length of stay (LOS) between and within hospitals over time, in order to
assess the room for efficiency improvement in hospital care. METHODS: Using Dutch
national individual patient-level hospital admission data, we studied LOS for
patients in nine groups of diagnoses and procedures between 1995 and 2010. We
fitted linear mixed effects models to the log-transformed LOS to disentangle
within and between hospital variation and to evaluate trends, adjusted for case
mix. RESULTS: We found substantial differences between diagnoses and procedures
in LOS variation and development over time, supporting our disease-specific
approach. For none of the diagnoses, relative variance decreased on the log
scale, suggesting room for further LOS reduction. Except for two procedures in
the same specialty, LOS of individual hospitals did not correlate between
diagnoses/procedures, indicating the absence of a hospital wide policy. We found
within-hospital variance to be many times greater than between-hospital variance.
This resulted in overlapping confidence intervals across most hospitals for
individual hospitals' performances in terms of LOS. CONCLUSIONS: The results
suggest room for efficiency improvement implying lower costs per patient treated.
It further implies a possibility to raise the number of patients treated using
the same capacity or to downsize the capacity. Furthermore, policymakers and
health care purchasers should take into account statistical uncertainty when
benchmarking LOS between hospitals and identifying inefficient hospitals.
PMID- 26423906
TI - Increased colorectal cancer incidence in Iran: a systematic review and meta
analysis.
AB - BACKGROUND: Colorectal cancer is the third most common cancer in Iran. The
increasing trend of colorectal cancer incidence in Iran and the close
relationship with the geographical location are the underlying reasons for this
study. METHODS: DATA SOURCE: Eleven databases, including MEDLINE, EMBASE,
SCOPUS, and four other databases, for articles in Persian were searched from
April 2014 to October 2014. Additional data were obtained from an online survey
of the Central Library of Tabriz Faculty of Medicine. STUDY ELIGIBILITY CRITERIA:
In this systematic review and meta-analysis, we included studies reporting
different measures of incidence, age-standardized incidence rates, and crude
incidence rates. All rates (per 100,000 person-years) were standardized to the
world standard population. STUDY APPRAISAL AND SYNTHESIS METHODS: A preliminary
review of the title and abstracts of these articles was used to exclude any that
were clearly irrelevant. The full text review determined whether the article was
relevant to our topic. All the potentially relevant manuscripts were reviewed by
two other investigators (S.D., M.G.). A total of 39 studies (10 Persian and 29
English articles) from different provinces and diverse areas of Iran, were
analyzed in this study using comprehensive meta-analysis software. For accuracy
studies, we used estimated rates for males and females with 95 % confidence
intervals. RESULTS: Age-standardized incidence rates were obtained based on the
random effects model and were 8.16 (95 % CI: 6.64 to 9.68) and 6.17 (95 % CI:
5.01 to 7.32) for males and females, respectively. The random crude rates were
5.58 (95 % CI: 4.22 to 6.94) for males and 4.01 (95 % CI: 3.06 to 4.97) for
females. CONCLUSIONS: Colorectal cancer incidence rates rise due to individual
and environmental risk factors as well as improvement in the registry system and
increase in access to health services. A more executed organized and structured
system for collecting cancer data, in all cities and rural areas of the country,
is an essential priority.
PMID- 26423907
TI - Superior cervical ganglion mimicking retropharyngeal adenopathy in head and neck
cancer patients: MRI features with anatomic, histologic, and surgical
correlation.
AB - INTRODUCTION: To describe the unique MRI findings of superior cervical ganglia
(SCG) that may help differentiate them from retropharyngeal lymph nodes (RPLNs).
METHODS: A retrospective review of post-treatment NPC patients from 1999 to 2012
identified three patients previously irradiated for NPC that were suspected of
having recurrent nodal disease in retropharyngeal lymph nodes during surveillance
MRI. Subsequent surgical exploration revealed enlarged SCG only; no
retropharyngeal nodal disease was found. A cadaveric head specimen was also
imaged with a 3T MRI before and after dissection. In addition, SCG were also
harvested from three cadaveric specimens and subjected to histologic analysis.
RESULTS: The SCG were found at the level of the C2 vertebral body, medial to the
ICA. They were ovoid on axial images and fusiform and elongated with tapered
margins in the coronal plane. T2-weighted (T2W) signal was hyperintense. No
central elevated T1-weighted (T1W) signal was seen within the ganglia in non-fat
saturated sequences to suggest the presence of a fatty hilum. Enhancement after
gadolinium was present. A central "black dot" was seen on axial T2W and post
contrast images in two of the three SCG demonstrated. Histology showed the
central black line was comprised of venules and interlacing neurites within the
central portion of the ganglion. CONCLUSIONS: The SCG can be mistaken for
enlarged RPLNs in post-treatment NPC patients. However, there are features which
can help differentiate them from RPLNs, preventing unnecessary therapy. These
imaging findings have not been previously described.
PMID- 26423908
TI - Poly(N-isopropylacrylamide-co-allylamine) (PNIPAM-co-ALA) nanospheres for the
thermally triggered release of Bacteriophage K.
AB - Due to the increased prevalence of resistant bacterial isolates which are no
longer susceptible to antibiotic treatment, recent emphasis has been placed on
finding alternative modes of treatment of wound infections. Bacteriophage have
long been investigated for their antimicrobial properties, yet the utilization of
phage therapy for the treatment of wound infections relies on a suitable delivery
system. Poly(N-isopropylacrylamide) (PNIPAM) is a thermally responsive polymer
which undergoes a temperature dependent phase transition at a critical solution
temperature. Bacteriophage K has been successfully formulated with PNIPAM
nanospheres copolymerized with allylamine (PNIPAM-co-ALA). By utilizing a
temperature responsive polymer it has been possible to engineer the nanospheres
to collapse at an elevated temperature associated with a bacterial skin
infection. The nanogels were reacted with surface deposited maleic anhydride in
order to anchor the nanogels to non-woven fabric. Bacteriophage incorporated
PNIPAM-co-ALA nanospheres demonstrated successful bacterial lysis of a clinically
relevant bacterial isolate - Staphylococcus aureus ST228 at 37 degrees C, whilst
bacterial growth was unaffected at 25 degrees C, thus providing a thermally
triggered release of bacteriophage.
PMID- 26423911
TI - Three-Dimensional Modeling May Improve Surgical Education and Clinical Practice.
AB - BACKGROUND: Three-dimensional (3D) printing has been used in the manufacturing
industry for rapid prototyping and product testing. The aim of our study was to
assess the feasibility of creating anatomical 3D models from a digital image
using 3D printers. Furthermore, we sought face validity of models and explored
potential opportunities for using 3D printing to enhance surgical education and
clinical practice. METHODS: Computed tomography and magnetic resonance images
were reviewed, converted to computer models, and printed by stereolithography to
create near exact replicas of human organs. Medical students and surgeons
provided feedback via survey at the 2014 Surgical Education Week conference.
RESULTS: There were 51 respondents, and 95.8% wanted these models for their
patients. Cost was a concern, but 82.6% found value in these models at a price
less than $500. All respondents thought the models would be useful for
integration into the medical school curriculum. CONCLUSION: Three-dimensional
printing is a potentially disruptive technology to improve both surgical
education and clinical practice. As the technology matures and cost decreases, we
envision 3D models being increasingly used in surgery.
PMID- 26423910
TI - Altered serotonin transporter binding potential in patients with obsessive
compulsive disorder under escitalopram treatment: [11C]DASB PET study.
AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental
illness. Selective serotonin reuptake inhibitors block serotonin transporters
(SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are
reported in drug-free patients with OCD, but it is not known what happens to SERT
levels during treatment. This is important as alterations in SERT levels in
patients under treatment could underlie poor response, or relapse during or after
treatment. The aim of the present study was first to validate a novel approach to
measuring SERT levels in people taking treatment and then to investigate SERT
binding potential (BP) using [11C]DASB PET in patients with OCD currently treated
with escitalopram in comparison with healthy controls. METHOD: Twelve patients
and age- and sex-matched healthy controls were enrolled. The patients and healthy
controls underwent serial PET scans after administration of escitalopram and
blood samples for drug concentrations were collected simultaneously with the
scans. Drug-free BPs were obtained by using an inhibitory E max model we
developed previously. RESULTS: The inhibitory E max model was able to accurately
predict drug-free SERT BP in people taking drug treatment. The drug-free BP in
patients with OCD currently treated with escitalopram was significantly different
from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen),
1.46 (thalamus), -5.67 (dorsal raphe nucleus)]. CONCLUSIONS: This result extends
previous findings showing SERT abnormalities in drug-free patients with OCD by
indicating that altered SERT availability is seen in OCD despite treatment. This
could account for poor response and the high risk of relapse in OCD.
PMID- 26423909
TI - Myocardial interstitial remodelling in non-ischaemic dilated cardiomyopathy:
insights from cardiovascular magnetic resonance.
AB - Myocardial remodelling involves not only the myocytes, but also non-myocyte cells
and the extracellular matrix, which constitutes around 6 % of the normal heart
and includes fluid, collagen and glycoproteins. In non-ischaemic dilated
cardiomyopathy (DCM), the cardiac interstitium increases as a result of diffuse
interstitial (microscopic) fibrosis, post-necrotic replacement (macroscopic)
fibrosis or myocardial oedema. The activation of the renin-angiotensin
aldosterone system is a major determinant of fibroblasts activation and collagen
deposition, with the transforming growth factor beta as the downstream signal
mediator. Endomyocardial biopsy still represents the current reference method for
interstitial and replacement myocardial fibrosis assessment, but cardiovascular
magnetic resonance (CMR) allows in vivo detection of macroscopic fibrosis with
post-contrast late enhancement imaging. Moreover, recent pre- and post-contrast
T1 mapping techniques provide a quantitative estimation of myocardial
interstitial remodelling, with potential diagnostic and prognostic clinical
utility. Here, we review the pathophysiological mechanisms of myocardial
interstitial remodelling in DCM, its non-invasive characterization with
biomarkers and with CMR, as well as the most recent studies about their clinical
utility.
PMID- 26423912
TI - Electrical Impedance Spectroscopy to Aid Parathyroid Identification and
Preservation in Central Compartment Neck Surgery: A Proof of Concept in a Rabbit
Model.
AB - BACKGROUND: Accurate identification of parathyroid glands during thyroid surgery
is crucial to avoid postthyroidectomy hypocalcemia. Electrical impedance
spectroscopy has the potential to differentiate between tissues of different
morphology. The aim of this study was to determine the electrical impedance
patterns of the thyroid, parathyroid, and other soft tissue structures in the
rabbit neck. METHODS: The central compartments were exposed in 9 freshly culled
New Zealand White rabbits. In situ and ex vivo electrical impedance was measured
from thyroid lobes, external parathyroid glands, adipose tissue, and strap muscle
using the APX100 device. Specimens of all identified glands were sent for
histopathology examination. RESULTS: Histology confirmed correct identification
of all excised thyroid and parathyroid glands. The impedance was higher for
thyroid tissue at lower frequencies and for parathyroid tissue at higher
frequencies. Ex vivo electrical impedance spectra were significantly higher
compared with the in situ spectra across all frequencies for thyroid and
parathyroid tissues (P < .001). The ratio of low to high frequency in situ
impedance of thyroid, parathyroid, and muscle was significantly different (P <
.001), allowing for differentiation between these tissues. CONCLUSION: The
electrical impedance spectra of rabbit thyroid and parathyroid glands are
distinct and different from each other and from skeletal muscle. If these results
are replicated in human tissue, they have the potential to improve patient
outcomes by achieving early identification and preservation of parathyroid
glands.
PMID- 26423913
TI - Risk of Adverse Vascular Events in Newly Diagnosed Glioblastoma Multiforme
Patients Treated with Bevacizumab: a Systematic Review and Meta-Analysis.
AB - Previous evidence suggests that the humanized anti-VEGF antibody bevacizumab
increases thrombosis risk in glioma patients. Here, we comprehensively assessed
the risk of adverse vascular events in adult glioma patients receiving
bevacizumab therapy. Systematic searches of MEDLINE, EMBASE, and the Cochrane
Library were conducted to find prospective phase II/III clinical trials on adult
bevacizumab-treated glioma patients and non-bevacizumab-treated controls that
reported data on adverse vascular events. Four high-quality trials were finally
included in the systematic review, scoring greater than or equal to 7/8 on the
Newcastle-Ottawa Scale. Three trials provided sufficient data for four meta
analytical comparisons between bevacizumab-treated and control groups of newly
diagnosed glioblastoma multiforme (GBM) patients: all-cause discontinuation,
thrombocytopenia, deep vein thrombosis (DVT), and pulmonary embolism. None of
these adverse outcomes were found to be significantly different between
bevacizumab-treated and control groups (P > 0.05); however, there was a trend
toward significance with regard to bevacizumab therapy and the risk of pulmonary
embolism (P = 0.07). As there was a trend toward significance with regard to
bevacizumab therapy and the risk of pulmonary embolism, anticoagulation may be
advisable in certain newly diagnosed adult GBM patients who display a history of
thromboembolism and/or more serious risk factors for thromboembolic events.
PMID- 26423914
TI - Telemedicine for Monitoring MS Activity and Progression.
AB - OPINION STATEMENT: Telemedicine (TM) is defined as the exchange of medical
information between two different physical places. The aims of TM are to provide
services that cannot easily be provided face-to-face and improve the efficiency
of existing ones. Multiple sclerosis (MS) is a chronic demyelinating disease
characterized by a heterogeneous array of symptoms that can lead to severe
impairment and may impact on accessibility to medical services, patient's ability
to function, and overall health-related quality of life (HRQoL). The use of TM to
clinically monitor MS patients has demonstrated benefits by improving HRQoL and
reducing associated medical costs. Patient-reported outcome (PRO) measures have
been used in TM interventions, registries, and cost-efficiency studies because
they offer valuable information about patient's perspective of MS disease burden.
Moreover, TM has shown acceptable reliability in the assessment of the
neurological impairment by Kurtzke expanded disability status scale (EDSS) and
has the potential to develop more sensitive measures, such as average daily
walking activity, to closely monitor MS disease progression in real environment.
It is likely that the use of TM will continue to increase in the following years
but larger and controlled studies are necessary to confirm the beneficial effects
of TM to deliver an optimal care for patients with MS.
PMID- 26423916
TI - [Osteoporosis].
PMID- 26423915
TI - A Randomized Controlled Trial of an Emergency Department Intervention for
Patients with Chronic Noncancer Pain.
AB - BACKGROUND: Emergency Departments (EDs) are beginning to notify their physicians
of patients reporting chronic noncancer pain (CNCP) who frequent EDs, and are
suggesting that the physicians not prescribe opioids to these patients.
OBJECTIVES: We hypothesized that this intervention would reduce both the number
of opioids prescribed to these patients by their ED physicians and the number of
these patients' return visits to the ED. METHODS: We conducted a randomized
controlled trial of this intervention in 13 electronically linked EDs. Patients
eligible for the study were characterized by CNCP, lacked evidence of sickle cell
anemia and suicide ideation, and made frequent (>10) visits to the EDs over a 12
month period. We randomly assigned 411 of these patients to either an
intervention group or a control group. Our intervention comprised both an alert
placed in eligible patients' medical files and letters sent to the patients and
their community-based providers. The alert suggested that physicians decline
requests for opioid analgesic prescriptions and instead refer these patients to
community-based providers to manage their ongoing pain. RESULTS: During the 12
months after randomization, patients in the intervention and control groups
averaged 11.9 and 16.6 return visits, and received prescriptions for opioids on
16% and 26% of those visits, respectively. Altogether, patients in the
intervention group made 1033 fewer return visits to the EDs in the follow-up year
than those in the control group. CONCLUSION: This intervention constitutes a
promising practice that EDs should consider to reduce the number of visits made
by frequent visitors with CNCP.
PMID- 26423917
TI - [Penetrating stab injury to the lumbar spinal cord in a child].
AB - This article reports the case of an 8-year-old boy with a knife stab injury to
the lumbar spine without neurological deficits. The computed tomography (CT) scan
revealed a longitudinal penetration of the conus medullaris at the level of the
first lumbar vertebra. The knife blade was extracted and primary closure was
carried out on the stab wound. The immediately postoperative magnetic resonance
imaging (MRI) as well as the follow-up examinations after 1 and 6 weeks showed no
evidence of compressive spinal bleeding, myelopathy or cerebrospinal fluid
leakage. In addition, no secondary changes of the neurological status developed.
Consequently, in cases of neurologically asymptomatic patients without
concomitant injuries the surgical exploration of a stab wound does not seem to be
absolutely necessary.
PMID- 26423918
TI - [Omission of osteoporosis diagnostics and therapy after fractures in the elderly
: an avoidable treatment error?].
AB - Through a more consistent diagnostics and treatment of osteoporosis, subsequent
fractures and associated complications could be reduced in aged patients. Whereas
anticoagulants are now standard in the treatment of fractures of the lower
extremities to prevent thromboembolic complications in orthopedic surgery and an
omission of anticoagulation can be regarded as medical malpractice, the
management of osteoporosis following such fractures is very frequently
disregarded. Although guidelines for osteoporosis, such as those from the
governing body on osteology (Dachverband Osteologie, DVO) from 2014 are not
legally binding as such, the breach of this standard of care can constitute a
breach of medical obligation by the physician. The omission of osteoporosis
diagnostics and initiation of treatment despite appropriate findings after
fractures in aged patients, could represent a diagnostic assessment error and
severe malpractice in the legal sense. In this case, evidence of a serious
malpractice could be associated with civil, criminal and professional claims
which could be linked with relevant legal consequences. Regardless of the legal
consequences for omission of osteoporosis management following multiple fractures
in aged patients, the management of osteoporosis should be an integral component
in the treatment of these patients in the future.
PMID- 26423919
TI - Variations in peak nasal inspiratory flow among healthy students after using
saline solutions.
AB - INTRODUCTION: Nasal hygiene with saline solutions has been shown to relieve
congestion, reduce the thickening of the mucus and keep nasal cavity clean and
moist. OBJECTIVE: Evaluating whether saline solutions improve nasal inspiratory
flow among healthy children. METHODS: Students between 8 and 11 years of age
underwent 6 procedures with saline solutions at different concentrations. The
peak nasal inspiratory flow was measured before and 30 min after each procedure.
Statistical analysis was performed by means of t test, analysis of variance, and
Tukey's test, considering p<0.05. RESULTS: We evaluated 124 children at all
stages. There were differences on the way a same concentration was used. There
was no difference between 0.9% saline solution and 3% saline solution by using a
syringe. CONCLUSION: The 3% saline solution had higher averages of peak nasal
inspiratory flow, but it was not significantly higher than the 0.9% saline
solution. It is important to offer various options to patients.
PMID- 26423920
TI - Reactivity of the Donor-Stabilized Silylenes [iPrNC(Ph)NiPr]2 Si and [iPrNC(NiPr2
)NiPr]2 Si: Activation of CO2 and CS2.
AB - Activation of CO2 by the bis(amidinato)silylene 1 and the analogous
bis(guanidinato)silylene 2 leads to the structurally analogous six-coordinate
silicon(IV) complexes 4 (previous work) and 8, respectively, the first silicon
compounds with a chelating carbonato ligand. Likewise, CS2 activation by silylene
1 affords the analogous six-coordinate silicon(IV) complex 10, the first silicon
compound with a chelating trithiocarbonato ligand. CS2 activation by silylene 2,
however, yields the five-coordinate silicon(IV) complex 13 with a carbon-bound
CS2 (2-) ligand, which also represents an unprecedented coordination mode in
silicon coordination chemistry. Treatment of the dinuclear silicon(IV) complexes
5 and 6 with CO2 also affords the six-coordinate carbonatosilicon(IV) complexes 4
and 8, respectively.
PMID- 26423921
TI - Patients' Experiences Using a Brief Screening Tool for Medication-Related
Problems in a Community Pharmacy Setting.
AB - OBJECTIVES: The objective of this study was to explore patient perceptions and
the practical implication of using a brief 9-item scale to screen for medication
related problems in community pharmacies. METHODS: Semistructured, audio
recorded, telephonic interviews were conducted with 40 patients who completed the
scale and reviewed its results with their pharmacist. Audio recordings were
transcribed verbatim and analyzed using qualitative methods to identify themes.
RESULTS: Patients generally reported the scale was simple to complete and could
be used easily in other community pharmacies. Participants shared they had
increased understanding of their medications and confidence that their medication
therapy was appropriate. Several patients reported having actual medication
related problems identified and resolved through the use of the scale. Patients
also reported improved relationships with pharmacists and heightened belief in
the value provided by pharmacists. CONCLUSIONS: This screening tool may have
value in increasing patients' understanding of and confidence in their
medications, enhancing pharmacist-patient relationships, and identifying problems
requiring additional interventions.
PMID- 26423922
TI - Comments on: Validity and Reliability of a Systematic Database Search Strategy to
Identify Publications Resulting From Pharmacy Residency Research Projects.
PMID- 26423923
TI - Localizing Carbohydrate Binding Sites in Proteins Using Hydrogen/Deuterium
Exchange Mass Spectrometry.
AB - The application of hydrogen/deuterium exchange mass spectrometry (HDX-MS) to
localize ligand binding sites in carbohydrate-binding proteins is described.
Proteins from three bacterial toxins, the B subunit homopentamers of Cholera
toxin and Shiga toxin type 1 and a fragment of Clostridium difficile toxin A, and
their interactions with native carbohydrate receptors, GM1 pentasaccharides (beta
Gal-(1->3)-beta-GalNAc-(1->4)[alpha-Neu5Ac-(2->3)]-beta-Gal-(1->4)-Glc), Pk
trisaccharide (alpha-Gal-(1->4)-beta-Gal-(1->4)-Glc) and CD-grease (alpha-Gal-(1
>3)-beta-Gal-(1->4)-beta-GlcNAcO(CH2)8CO2CH3), respectively, served as model
systems for this study. Comparison of the differences in deuterium uptake for
peptic peptides produced in the absence and presence of ligand revealed regions
of the proteins that are protected against deuterium exchange upon ligand
binding. Notably, protected regions generally coincide with the carbohydrate
binding sites identified by X-ray crystallography. However, ligand binding can
also result in increased deuterium exchange in other parts of the protein,
presumably through allosteric effects. Overall, the results of this study suggest
that HDX-MS can serve as a useful tool for localizing the ligand binding sites in
carbohydrate-binding proteins. However, a detailed interpretation of the changes
in deuterium exchange upon ligand binding can be challenging because of the
presence of ligand-induced changes in protein structure and dynamics.
PMID- 26423924
TI - Genetic investigation of sudden unexpected death in epilepsy cohort by panel
target resequencing.
AB - Sudden unexpected death in epilepsy (SUDEP) is defined as the abrupt, no
traumatic, witnessed or unwitnessed death, occurring in benign circumstances, in
an individual with epilepsy, with or without evidence for a seizure and excluding
documented status epilepticus (seizure duration >= 30 min or seizures without
recovery), and in which postmortem examination does not reveal a cause of death.
Although the physiopathological mechanisms that underlie SUDEP remain to be
clarified, the genetic background has been described to play a role in this
disorder. Pathogenic variants in genes associated with epilepsy and encoding
cardiac ion channels could explain the SUDEP phenotype. To test this we use the
next-generation sequencing technology to sequence a cohort of SUDEP cases and its
translation into clinical and forensic fields. A panel target resequencing was
used to study 14 SUDEP cases from both postmortem (2 cases) and from living
patients (12 cases). Genes already associated with SUDEP and also candidate genes
had been investigated. Overall, 24 rare genetic variants were identified in 13
SUDEP cases. Four cases showed rare variants with complete segregation in the
SCN1A, FBN1, HCN1, SCN4A, and EFHC1 genes, and one case with a rare variant in
KCNQ1 gene showed incomplete pattern of inheritance. In four cases, rare variants
were detected in CACNA1A, SCN11A and SCN10A, and KCNQ1 genes, but familial
segregation was not possible due to lack of DNA from relatives. Finally, in the
four remaining cases, the rare variants did not segregate in the family. This
study confirms the link between epilepsy, sudden death, and cardiac disease. In
addition, we identified new potential candidate genes for SUDEP: FBN1, HCN1,
SCN4A, EFHC1, CACNA1A, SCN11A, and SCN10A. Further confirmation in larger cohorts
will be necessary especially if genetic screening for SUDEP is applied to
forensic and clinical medicine. Nevertheless, this study supports the emerging
concept of a genetically determined cardiocerebral channelopathy.
PMID- 26423925
TI - Hereditary spastic paraplegia with recessive trait caused by mutation in KLC4
gene.
AB - We report an association between a new causative gene and spastic paraplegia,
which is a genetically heterogeneous disorder. Clinical phenotyping of one
consanguineous family followed by combined homozygosity mapping and whole-exome
sequencing analysis. Three patients from the same family shared common features
of progressive complicated spastic paraplegia. They shared a single homozygous
stretch area on chromosome 6. Whole-exome sequencing revealed a homozygous
mutation (c.853_871del19) in the gene coding the kinesin light chain 4 protein
(KLC4). Meanwhile, the unaffected parents and two siblings were heterozygous and
one sibling was homozygous wild type. The 19 bp deletion in exon 6 generates a
stop codon and thus a truncated messenger RNA and protein. The association of a
KLC4 mutation with spastic paraplegia identifies a new locus for the disease.
PMID- 26423926
TI - Comparison of genetic variation in drug ADME-related genes in Thais with
Caucasian, African and Asian HapMap populations.
AB - The objectives of this study are to investigate allele frequencies of drug
absorption, distribution, metabolism and elimination (ADME)-related genes in the
Thai population and to compare these genes to HapMap populations including
Caucasians (CEU), Africans (YRI) and Asians (CHB/JPT). Genetic variations of drug
ADME-related genes in 190 Thais were investigated using drug metabolizing enzymes
and transporters (DMET) plus genotyping system. We examined 1936 single
nucleotide polymorphisms (SNPs) of 225 genes that have documented functional and
clinical significances in phase I and phase II drug metabolism enzymes, drug
transporters and other genes involved in ADME processes. Distributions of
genotyping data from Thai were compared with other HapMap populations including
Caucasian, African and Asian populations. The analysis demonstrated 43 SNPs with
statistical significance comparing among five populations. However, only 26 SNPs
showed statistical significance in pair-wise comparisons between Thai versus CEU
and Thai versus CHB/JPT. These 26 SNPs belong to 13 groups of drug ADME-related
genes which are CYP2A6, CYP3A5, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, VKORC1,
COMT, NAT2, TPMT, UGT1A1 and SLCO1B1. These genes demonstrated clinical
significances as previously observed in many studies. The results could explain
clinical variability in pharmacokinetics and pharmacodynamics of drugs in Thais
based on genetic variations in drug ADME-related gene emphasized in this article.
PMID- 26423927
TI - Environmentally persistent free radical-containing particulate matter
competitively inhibits metabolism by cytochrome P450 1A2.
AB - Combustion processes generate different types of particulate matter (PM) that can
have deleterious effects on the pulmonary and cardiovascular systems.
Environmentally persistent free radicals (EPFRs) represent a type of particulate
matter that is generated after combustion of environmental wastes in the presence
of redox-active metals and aromatic hydrocarbons. Cytochromes P450 (P450/CYP) are
membrane-bound enzymes that are essential for the phase I metabolism of most
lipophilic xenobiotics. The EPFR formed by chemisorption of 2-monochlorophenol to
silica containing 5% copper oxide (MCP230) has been shown to generally inhibit
the activities of different forms of P450s without affecting those of cytochrome
P450 reductase and heme oxygenase-1. The mechanism of inhibition of rat liver
microsomal CYP2D2 and purified rabbit CYP2B4 by MCP230 has been shown previously
to be noncompetitive with respect to substrate. In this study, MCP230 was shown
to competitively inhibit metabolism of 7-benzyl-4-trifluoromethylcoumarin and 7
ethoxyresorufin by the purified, reconstituted rabbit CYP1A2. MCP230 is at least
5- and 50-fold more potent as an inhibitor of CYP1A2 than silica containing 5%
copper oxide and silica, respectively. Thus, even though PM generally inhibit
multiple forms of P450, PM interacts differently with the forms of P450 resulting
in different mechanisms of inhibition. P450s function as oligomeric complexes
within the membrane. We also determined the mechanism by which PM inhibited
metabolism by the mixed CYP1A2-CYP2B4 complex and found that the mechanism was
purely competitive suggesting that the CYP2B4 is dramatically inhibited when
bound to CYP1A2.
PMID- 26423929
TI - Addiction, Voluntary Choice, and Informed Consent: A Reply to Uusitalo and
Broers.
AB - In an earlier article in this journal I argued that the question of whether
heroin addicts can give voluntary consent to take part in research which involves
giving them a choice of free heroin does not - in contrast with a common
assumption in the bioethics literature - depend exclusively on whether or not
they possess the capacity to resist their desire for heroin. In some cases,
circumstances and beliefs might undermine the voluntariness of the choices a
person makes even if they do possess a capacity for self-control. Based on what I
took to be a plausible definition of voluntariness, I argued that the
circumstances and beliefs typical of many vulnerable heroin addicts are such that
we have good reasons to suspect they cannot give voluntary consent to take part
in such research, even assuming their desire for heroin is not irresistible. In a
recent article in this journal, Uusitalo and Broers object to this on the grounds
that I misdescribe heroin addicts' options set, that the definition of
voluntariness on which I rely is unrealistic and too demanding, and, more
generally, that my view of heroin addiction is flawed. I think their arguments
derive from a misunderstanding of the view I expressed in my article. In what
follows I hope therefore to clarify my position.
PMID- 26423928
TI - Increased risk of stroke with darbepoetin alfa in anaemic heart failure patients
with diabetes and chronic kidney disease.
AB - AIMS: The use of an erythropoesis-stimulating agent, darbepoetin alfa (DA), to
treat anaemia in patients with diabetes mellitus and chronic kidney disease was
associated with a heightened risk of stroke and neutral efficacy in the Trial to
Reduce Cardiovascular Events with Aranesp Therapy (TREAT), despite
epidemiological data suggesting the contrary. However, this association has not
been evaluated in another randomized, placebo-controlled trial. METHODS AND
RESULTS: Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) was a
randomized placebo-controlled trial of DA in 2278 patients with systolic heart
failure and anaemia, enrolled from 2006 to 2012 and followed for a median of 28
months. Within RED-HF, 816 patients had diabetes mellitus and chronic kidney
disease [estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m(2) ] and
met inclusion criteria for TREAT. TREAT-like RED-HF patient data were analysed
alone and combined at the patient level with the 4038 TREAT patients. In RED-HF,
the annualized event rate of stroke was 2.3 in patients on DA and 1.1 in patients
randomized to placebo (P = 0.051). Analysis of the combined group (n = 4854)
confirmed a nearly two-fold increase in stroke risk [hazard ratio (HR) 1.94, 95%
confidence interval (CI) 1.43-2.63] and an overall neutral effect on mortality
(HR 1.00, 95% CI 0.89-1.12) of raising haemoglobin with DA. CONCLUSION: The
placebo-controlled cohort of heart failure patients with anaemia, diabetes
mellitus, and chronic kidney disease from RED-HF provides confirmation of the
increased stroke risk associated with DA use identified in TREAT.
PMID- 26423930
TI - Centrocentral Short Circuiting for Management of Stump Neuroma Pain in Amputees.
PMID- 26423931
TI - Microsurgical Fenestration and Paraspinal Muscle Pedicle Flaps for the Treatment
of Symptomatic Sacral Tarlov Cysts.
AB - OBJECTIVE: Sacral Tarlov cysts are rare causes of sciatic and sacrococcygeal pain
and neurologic deficits. Although several microsurgical treatments have been
described, the optimal treatment has yet to be determined. We describe our
initial experience with symptomatic lesions combining 1) cyst fenestration and
imbrication and 2) filling the epidural space using vascularized paraspinous
muscle flaps rotated into the cystic cavity. METHODS: We retrospectively reviewed
all consecutive cases of symptomatic giant sacral Tarlov cysts treated with
microsurgery at our institution between 2003 and 2011. The main outcome measure
was self-reported symptom relief. Postoperative imaging, surgical complications,
and subsequent treatments were also recorded. RESULTS: Thirty-five patients were
treated. Mean age was 52 years. All patients presented with a chief complaint of
sacral-perineal pain. The mean cyst size was 3.6 cm (largest diameter). Follow-up
beyond the initial hospital stay was available in 86% (median 8 months). Ninety
three percent reported improvement in pain at some point during the postoperative
course but 50% of those developed recurrent pain symptoms. Postoperative imaging
was available in 69% of the patients in whom 92% showed complete obliteration
(25%) or reduction in cyst size (67%). CONCLUSIONS: The combination of
microsurgical cyst fenestration and the use of vascularized muscle pedicle flaps
to fill the cystic cavity and the epidural space results in obliteration or
reduction in size of the majority of cysts and is associated with initial
improvement in pain in most patients. However, delayed recurrence of pain was
common with this technique.
PMID- 26423932
TI - The immunomodulatory oligodendrocyte.
AB - Oligodendrocytes, the myelinating glial cells of the central nervous system
(CNS), are due to their high specialization and metabolic needs highly vulnerable
to various insults. This led to a general view that oligodendrocytes are
defenseless victims during brain damage such as occurs in acute and chronic CNS
inflammation. However, this view is challenged by increasing evidence that
oligodendrocytes are capable of expressing a wide range of immunomodulatory
molecules. They express various cytokines and chemokines (e.g. Il-1beta, Il17A,
CCL2, CXCL10), antigen presenting molecules (MHC class I and II) and co
stimulatory molecules (e.g. CD9, CD81), complement and complement receptor
molecules (e.g. C1s, C2 and C3, C1R), complement regulatory molecules (e.g. CD46,
CD55, CD59), tetraspanins (e.g. TSPAN2), neuroimmune regulatory proteins (e.g.
CD200, CD47) as well as extracellular matrix proteins (e.g. VCAN) and many
others. Their potential immunomodulatory properties can, at specific times and
locations, influence ongoing immune processes as shown by numerous publications.
Therefore, oligodendrocytes are well capable of immunomodulation, especially
during the initiation or resolution of immune processes in which subtle signaling
might tip the scale. A better understanding of the immunomodulatory
oligodendrocyte can help to invent new, innovative therapeutic interventions in
various diseases such as Multiple Sclerosis. This article is part of a Special
Issue entitled SI: Myelin Evolution.
PMID- 26423933
TI - MicroRNA-574 is involved in cognitive impairment in 5-month-old APP/PS1 mice
through regulation of neuritin.
AB - Alzheimer's disease (AD) is the most common form of dementia in the elderly. The
recent evidence in AD research suggests that alterations in the microRNA (miRNA)
could contribute to risk for the disease. However, little is understood about the
roles of miRNAs in cognitive impairment of early Alzheimer's disease (AD). Here,
we used 5-month-old APP/PS1 mice, which mimic many of the salient features of the
early stage of AD pathological process, to further investigate the roles of
miRNAs in synaptic loss involved in learning and memory. We used miRNA expression
microarrays on RNA extracted from the hippocampus of 5-month-old APP/PS1 mice and
wild type mice. Real-time reverse transcription PCR was conducted to verify the
candidate miRNAs discovered by microarray analysis. The data showed that miR-574
was increased significantly in the hippocampus of 5-month-old APP/PS1 mice, which
were concomitant with that APP/PS1 mice at the same age displayed a significant
synaptic loss and cognitive deficits. Bioinformatic analysis predicted that
neuritin (Nrn1) mRNA is targeted by miR-574. Overexpression of miR-574 lowers the
levels of neuritin and synaptic proteins expression in primary hippocampal
neurons damage induced by Abeta25-35. And the expression of miR-574 was also up
regulated in the hippocampal neurons from APP/PS1 mice compared with WT
littermates. In contrast, suppression of miR-574 by miR-574 inhibitor
significantly results in higher levels of neuritin and synaptic proteins
expression. Taken together, miR-574 is involved in cognitive impairment in 5
month-old APP/PS1 mice through regulation of neuritin.
PMID- 26423934
TI - Reverse engineering human neurodegenerative disease using pluripotent stem cell
technology.
AB - With the technology of reprogramming somatic cells by introducing defined
transcription factors that enables the generation of "induced pluripotent stem
cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells
(ESCs), it has become possible to use this technology to produce various cells
and tissues that have been difficult to obtain from living bodies. This
advancement is bringing forth rapid progress in iPSC-based disease modeling, drug
screening, and regenerative medicine. More and more studies have demonstrated
that phenotypes of adult-onset neurodegenerative disorders could be rather
faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite
the adult-onset nature of the diseases, pathogenic phenotypes and cellular
abnormalities often exist in early developmental stages, providing new "windows
of opportunity" for understanding mechanisms underlying neurodegenerative
disorders and for discovering new medicines. The cell reprogramming technology
enables a reverse engineering approach for modeling the cellular degenerative
phenotypes of a wide range of human disorders. An excellent example is the study
of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using
iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss
of upper and lower motor neurons (MNs), culminating in muscle wasting and death
from respiratory failure. The iPSC approach provides innovative cell culture
platforms to serve as ALS patient-derived model systems. Researchers have
converted iPSCs derived from ALS patients into MNs and various types of glial
cells, all of which are involved in ALS, to study the disease. The iPSC
technology could be used to determine the role of specific genetic factors to
track down what's wrong in the neurodegenerative disease process in the "disease
in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific
genes in human ESCs could also be performed to control and to complement the iPSC
based approach for ALS disease modeling studies. Much knowledge has been
generated from the study of both ALS iPSCs and ESCs. As these methods have
advantages and disadvantages that should be balanced on experimental design in
order for them to complement one another, combining the diverse methods would
help build an expanded knowledge of ALS pathophysiology. The goals are to reverse
engineer the human disease using ESCs and iPSCs, generate lineage reporter lines
and in vitro disease models, target disease related genes, in order to better
understand the molecular and cellular mechanisms of differentiation regulation
along neural (neuronal versus glial) lineages, to unravel the pathogenesis of the
neurodegenerative disease, and to provide appropriate cell sources for
replacement therapy. This article is part of a Special Issue entitled SI: PSC and
the brain.
PMID- 26423935
TI - Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and
Alzheimer's and Parkinson's diseases.
AB - Several neurological and psychiatric disorders present hyperexcitability of
neurons in specific regions of the brain or spinal cord, partly because of some
loss and/or dysfunction of gamma-amino butyric acid positive (GABA-ergic)
inhibitory interneurons. Strategies that enhance inhibitory neurotransmission in
the affected brain regions may therefore ease several or most deficits linked to
these disorders. This perception has incited a huge interest in testing the
efficacy of GABA-ergic interneuron cell grafting into regions of the brain or
spinal cord exhibiting hyperexcitability, dearth of GABA-ergic interneurons or
impaired inhibitory neurotransmission, using preclinical models of neurological
and psychiatric disorders. Interneuron progenitors from the embryonic ventral
telencephalon capable of differentiating into diverse subclasses of interneurons
have particularly received much consideration because of their ability for
dispersion, migration and integration with the host neural circuitry after
grafting. The goal of this review is to discuss the premise, scope and
advancement of GABA-ergic cell therapy for easing neurological deficits in
preclinical models of schizophrenia, chronic neuropathic pain, Alzheimer's
disease and Parkinson's disease. As grafting studies in these prototypes have so
far utilized either primary cells from the embryonic medial and lateral
ganglionic eminences or neural progenitor cells expanded from these eminences as
donor material, the proficiency of these cell types is highlighted. Moreover,
future studies that are essential prior to considering the possible clinical
application of these cells for the above neurological conditions are proposed.
Particularly, the need for grafting studies utilizing medial ganglionic eminence
like progenitors generated from human pluripotent stem cells via directed
differentiation approaches or somatic cells through direct reprogramming methods
are emphasized. This article is part of a Special Issue entitled SI: PSC and the
brain.
PMID- 26423937
TI - Schwann cells and their transcriptional network: Evolution of key regulators of
peripheral myelination.
AB - As derivatives of the neural crest, Schwann cells represent a vertebrate
invention. Their development and differentiation is under control of a newly
constructed, vertebrate-specific regulatory network that contains Sox10, Oct6 and
Krox20 as cornerstones and central regulators of peripheral myelination. In this
review, we discuss the function and relationship of these transcription factors
among each other and in the context of their regulatory network, and present
ideas of how neofunctionalization may have helped to recruit them to their novel
task in Schwann cells. This article is part of a Special Issue entitled SI:
Myelin Evolution.
PMID- 26423936
TI - Exacerbation of Charcot-Marie-Tooth type 2E neuropathy following traumatic nerve
injury.
AB - Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral
neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait,
sensory defects, and deafness. We generated a novel line of CMT2E mice expressing
hNF-L(E397K), which displayed muscle atrophy of the lower limbs without
denervation, proximal reduction in large caliber axons, and decreased nerve
conduction velocity. In this study, we challenged wild type, hNF-L and hNF
L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional
recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF
L(E397K) mice demonstrated reduced recovery from nerve injury consistent with
increased susceptibility to neuropathy observed in CMT patients. In addition, hNF
L(E397K) developed a permanent reduction in their ability to weight bear,
increased mechanical allodynia, and premature gait shift in the injured limb,
which led to increasingly disrupted interlimb coordination in hNF-L(E397K).
Exacerbation of neuropathy after injury and identification of gait alterations in
combination with previously described pathology suggests that hNF-L(E397K) mice
recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K)
mice provide a model for determining the efficacy of novel therapies.
PMID- 26423938
TI - Acute Ebola virus disease patient treatment and health-related quality of life in
health care professionals: A controlled study.
AB - OBJECTIVE: This study aimed to identify predictors of health-related quality of
life (HrQoL) and to investigate infection-related concerns in health
professionals during the acute treatment episode for one Ebola virus disease
(EVD) patient in tertiary care. METHODS: In a cross-sectional controlled study,
validated self-report questionnaires were completed by three groups of health
care professionals: (1) staff from standard internal medicine inpatient wards of
a tertiary care center, (2) staff from the isolation unit of the same center
responsible for Ebola patient treatment, and (3) staff from a research laboratory
with contact to the Ebola virus and other highly infectious pathogens. Outcomes
were HrQoL (SF-12), infection-related concerns, global health status, fatigue
(FACIT), depression (PHQ-9), anxiety (GAD-7), and somatic symptoms (SSS-8).
RESULTS: Comparisons between groups (n1=42, n2=32, n3=12) yielded no significant
differences in HrQoL, subjective risk of infection, and most other psychosocial
variables. However, the Ebola patient treatment group experienced significantly
higher levels of social isolation than both other groups. The best predictors of
poor physical and mental HrQoL were perceived lack of knowledge about the Ebola
virus disease (physical: B=-1.2, p=0.05; mental: B=-1.3, p=0.03) and fatigue
(physical: B=-0.3, p=0.02; mental: B=-0.53, p<0.001). CONCLUSION: Ebola patient
treatment in tertiary care does not seem to be associated with lower HrQoL and
enhanced subjective risk of infection, but seems to yield feelings of social
isolation in health-care professionals.
PMID- 26423939
TI - Predicting client attendance at further treatment following drug and alcohol
detoxification: Theory of Planned Behaviour and Implementation Intentions.
AB - INTRODUCTION AND AIMS: Despite clinical recommendations that further treatment is
critical for successful recovery following drug and alcohol detoxification, a
large proportion of clients fail to attend treatment after detoxification. In
this study, individual factors and constructs based on motivational and
volitional models of health behaviour were examined as predictors of post
detoxification treatment attendance. DESIGN AND METHODS: The sample consisted of
220 substance-dependent individuals participating in short-term detoxification
programs provided by The Australian Salvation Army. The Theory of Planned
Behaviour and Implementation Intentions were used to predict attendance at
subsequent treatment. RESULTS: Follow-up data were collected for 177 participants
(81%), with 104 (80%) of those participants reporting that they had either
attended further formal treatment (e.g. residential rehabilitation programs,
outpatient counselling) or mutual support groups in the 2 weeks after leaving the
detoxification program. Logistic regression examined the predictors of further
treatment attendance. The full model accounted for 21% of the variance in
treatment attendance, with attitude and Implementation Intentions contributing
significantly to the prediction. DISCUSSION AND CONCLUSIONS: Findings from the
present study would suggest that assisting clients to develop a specific
treatment plan, as well as helping clients to build positive perceptions about
subsequent treatment, will promote greater attendance at further treatment
following detoxification. [Kelly PJ, Leung J, Deane FP, Lyons GCB. Predicting
client attendance at further treatment following drug and alcohol detoxification:
Theory of Planned Behaviour and Implementation Intentions. Drug Alcohol Rev
2016;35:678-685].
PMID- 26423940
TI - Induction and Antagonism of Antiviral Responses in Respiratory Syncytial Virus
Infected Pediatric Airway Epithelium.
AB - Airway epithelium is the primary target of many respiratory viruses. However,
virus induction and antagonism of host responses by human airway epithelium
remains poorly understood. To address this, we developed a model of respiratory
syncytial virus (RSV) infection based on well-differentiated pediatric primary
bronchial epithelial cell cultures (WD-PBECs) that mimics hallmarks of RSV
disease in infants. RSV is the most important respiratory viral pathogen in young
infants worldwide. We found that RSV induces a potent antiviral state in WD-PBECs
that was mediated in part by secreted factors, including interferon lambda 1 (IFN
lambda1)/interleukin-29 (IL-29). In contrast, type I IFNs were not detected
following RSV infection of WD-PBECs. IFN responses in RSV-infected WD-PBECs
reflected those in lower airway samples from RSV-hospitalized infants. In view of
the prominence of IL-29, we determined whether recombinant IL-29 treatment of WD
PBECs before or after infection abrogated RSV replication. Interestingly, IL-29
demonstrated prophylactic, but not therapeutic, potential against RSV. The
absence of therapeutic potential reflected effective RSV antagonism of IFN
mediated antiviral responses in infected cells. Our data are consistent with RSV
nonstructural proteins 1 and/or 2 perturbing the Jak-STAT signaling pathway, with
concomitant reduced expression of antiviral effector molecules, such as MxA/B.
Antagonism of Jak-STAT signaling was restricted to RSV-infected cells in WD-PBEC
cultures. Importantly, our study provides the rationale to further explore IL-29
as a novel RSV prophylactic. IMPORTANCE: Most respiratory viruses target airway
epithelium for infection and replication, which is central to causing disease.
However, for most human viruses we have a poor understanding of their
interactions with human airway epithelium. Respiratory syncytial virus (RSV) is
the most important viral pathogen of young infants. To help understand RSV
interactions with pediatric airway epithelium, we previously developed three
dimensional primary cell cultures from infant bronchial epithelium that reproduce
several hallmarks of RSV infection in infants, indicating that they represent
authentic surrogates of RSV infection in infants. We found that RSV induced a
potent antiviral state in these cultures and that a type III interferon,
interleukin IL-29 (IL-29), was involved. Indeed, our data suggest that IL-29 has
potential to prevent RSV disease. However, we also demonstrated that RSV
efficiently circumvents this antiviral immune response and identified mechanisms
by which this may occur. Our study provides new insights into RSV interaction
with pediatric airway epithelium.
PMID- 26423941
TI - Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at
the Level of Virus Entry and at a Late Stage in the Virus Life Cycle.
AB - Airway epithelial cells are susceptible to infection with seasonal influenza A
viruses (IAV), resulting in productive virus replication and release. Macrophages
(MPhi) are also permissive to IAV infection; however, virus replication is
abortive. Currently, it is unclear how productive infection of MPhi is impaired
or the extent to which seasonal IAV replicate in MPhi. Herein, we compared mouse
MPhi and epithelial cells for their ability to support genomic replication and
transcription, synthesis of viral proteins, assembly of virions, and release of
infectious progeny following exposure to genetically defined IAV. We confirm that
seasonal IAV differ in their ability to utilize cell surface receptors for
infectious entry and that this represents one level of virus restriction.
Following virus entry, we demonstrate synthesis of all eight segments of genomic
viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV
infected mouse MPhi. Although newly synthesized hemagglutinin (HA) and
neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and
expressed at the cell surface, electron microscopy confirmed that virus assembly
was defective in IAV-infected MPhi, defining a second level of restriction late
in the virus life cycle. IMPORTANCE: Seasonal influenza A viruses (IAV) and
highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only
HPAI replicate productively in these cells. Herein, we demonstrate that impaired
virus uptake into macrophages represents one level of restriction limiting
infection by seasonal IAV. Following uptake, seasonal IAV do not complete
productive replication in macrophages, representing a second level of
restriction. Using murine macrophages, we demonstrate that productive infection
is blocked late in the virus life cycle, such that virus assembly is defective
and newly synthesized virions are not released. These studies represent an
important step toward identifying host-encoded factors that block replication of
seasonal IAV, but not HPAI, in macrophages.
PMID- 26423942
TI - MDA5 Is Critical to Host Defense during Infection with Murine Coronavirus.
AB - Infection with the murine coronavirus mouse hepatitis virus (MHV) activates the
pattern recognition receptors melanoma differentiation-associated gene 5 (MDA5)
and Toll-like receptor 7 (TLR7) to induce transcription of type I interferon.
Type I interferon is crucial for control of viral replication and spread in the
natural host, but the specific contributions of MDA5 signaling to this pathway as
well as to pathogenesis and subsequent immune responses are largely unknown. In
this study, we use MHV infection of the liver as a model to demonstrate that MDA5
signaling is critically important for controlling MHV-induced pathology and
regulation of the immune response. Mice deficient in MDA5 expression (MDA5(-/-)
mice) experienced more severe disease following MHV infection, with reduced
survival, increased spread of virus to additional sites of infection, and more
extensive liver damage than did wild-type mice. Although type I interferon
transcription decreased in MDA5(-/-) mice, the interferon-stimulated gene
response remained intact. Cytokine production by innate and adaptive immune cells
was largely intact in MDA5(-/-) mice, but perforin induction by natural killer
cells and levels of interferon gamma, interleukin-6 (IL-6), and tumor necrosis
factor alpha (TNF-alpha) in serum were elevated. These data suggest that MDA5
signaling reduces the severity of MHV-induced disease, at least in part by
reducing the intensity of the proinflammatory cytokine response. IMPORTANCE:
Multicellular organisms employ a wide range of sensors to detect viruses and
other pathogens. One such sensor, MDA5, detects viral RNA and triggers induction
of type I interferons, chemical messengers that induce inflammation and help
regulate the immune responses. In this study, we sought to determine the role of
MDA5 during infection with mouse hepatitis virus, a murine coronavirus used to
model viral hepatitis as well as other human diseases. We found that mice lacking
the MDA5 sensor were more susceptible to infection than were mice with MDA5 and
experienced decreased survival. Viral replication in the liver was similar in
mice with and without MDA5, but liver damage was increased in MDA5(-/-) mice,
suggesting that the immune response is causing the damage. Production of several
proinflammatory cytokines was elevated in MDA5(-/-) mice, suggesting that MDA5
may be responsible for keeping pathological inflammatory responses in check.
PMID- 26423943
TI - Contribution of Epidemiological Predictors in Unraveling the Phylogeographic
History of HIV-1 Subtype C in Brazil.
AB - The phylogeographic history of the Brazilian HIV-1 subtype C (HIV-1C) epidemic is
still unclear. Previous studies have mainly focused on the capital cities of
Brazilian federal states, and the fact that HIV-1C infections increase at a
higher rate than subtype B infections in Brazil calls for a better understanding
of the process of spatial spread. A comprehensive sequence data set sampled
across 22 Brazilian locations was assembled and analyzed. A Bayesian
phylogeographic generalized linear model approach was used to reconstruct the
spatiotemporal history of HIV-1C in Brazil, considering several potential
explanatory predictors of the viral diffusion process. Analyses were performed on
several subsampled data sets in order to mitigate potential sample biases. We
reveal a central role for the city of Porto Alegre, the capital of the
southernmost state, in the Brazilian HIV-1C epidemic (HIV-1C_BR), and the
northward expansion of HIV-1C_BR could be linked to source populations with
higher HIV-1 burdens and larger proportions of HIV-1C infections. The results
presented here bring new insights to the continuing discussion about the HIV-1C
epidemic in Brazil and raise an alternative hypothesis for its spatiotemporal
history. The current work also highlights how sampling bias can confound
phylogeographic analyses and demonstrates the importance of incorporating
external information to protect against this. IMPORTANCE: Subtype C is
responsible for the largest HIV infection burden worldwide, but our understanding
of its transmission dynamics remains incomplete. Brazil witnessed a relatively
recent introduction of HIV-1C compared to HIV-1B, but it swiftly spread
throughout the south, where it now circulates as the dominant variant. The
northward spread has been comparatively slow, and HIV-1B still prevails in that
region. While epidemiological data and viral genetic analyses have both
independently shed light on the dynamics of spread in isolation, their
combination has not yet been explored. Here, we complement publically available
sequences and new genetic data from 13 cities with epidemiological data to
reconstruct the history of HIV-1C spread in Brazil. The combined approach results
in more robust reconstructions and can protect against sampling bias. We found
evidence for an alternative view of the HIV-1C spatiotemporal history in Brazil
that, contrary to previous explanations, integrates seamlessly with other
observational data.
PMID- 26423944
TI - Intercellular Transmission of Viral Populations with Vesicles.
AB - A common paradigm holds that during cell-to-cell transmission, viruses behave as
lone soldiers. Recently, we discovered not only that enteroviruses are
transmitted via vesicles as populations of viral particles but also that this
type of transmission enhances their infection efficiency (Y. H. Chen et al., Cell
160: 619-630, 2015). This mechanism could be advantageous for the overall fitness
of the viral population, promoting genetic interplay by enabling viral
quasispecies to collectively infect a susceptible host cell. Here, we discuss
these findings in the context of viral pathogenesis and also propose that this
novel type of vesicular transmission is widespread among different virus families
and includes populations of both viral particles and naked viral genomes.
PMID- 26423945
TI - Differential Inhibition of Macrophage Activation by Lymphocytic Choriomeningitis
Virus and Pichinde Virus Is Mediated by the Z Protein N-Terminal Domain.
AB - Several arenavirus pathogens, such as Lassa and Junin viruses, inhibit macrophage
activation, the molecular mechanism of which is unclear. We show that lymphocytic
choriomeningitis virus (LCMV) can also inhibit macrophage activation, in contrast
to Pichinde and Tacaribe viruses, which are not known to naturally cause human
diseases. Using a recombinant Pichinde virus system, we show that the LCMV Z N
terminal domain (NTD) mediates the inhibition of macrophage activation and immune
functions.
PMID- 26423946
TI - Flavivirus Infection Impairs Peroxisome Biogenesis and Early Antiviral Signaling.
AB - Flaviviruses are significant human pathogens that have an enormous impact on the
global health burden. Currently, there are very few vaccines against or
therapeutic treatments for flaviviruses, and our understanding of how these
viruses cause disease is limited. Evidence suggests that the capsid proteins of
flaviviruses play critical nonstructural roles during infection, and therefore,
elucidating how these viral proteins affect cellular signaling pathways could
lead to novel targets for antiviral therapy. We used affinity purification to
identify host cell proteins that interact with the capsid proteins of West Nile
and dengue viruses. One of the cellular proteins that formed a stable complex
with flavivirus capsid proteins is the peroxisome biogenesis factor Pex19.
Intriguingly, flavivirus infection resulted in a significant loss of peroxisomes,
an effect that may be due in part to capsid expression. We posited that capsid
protein-mediated sequestration and/or degradation of Pex19 results in loss of
peroxisomes, a situation that could result in reduced early antiviral signaling.
In support of this hypothesis, we observed that induction of the lambda
interferon mRNA in response to a viral RNA mimic was reduced by more than 80%.
Together, our findings indicate that inhibition of peroxisome biogenesis may be a
novel mechanism by which flaviviruses evade the innate immune system during early
stages of infection. IMPORTANCE: RNA viruses infect hundreds of millions of
people each year, causing significant morbidity and mortality. Chief among these
pathogens are the flaviviruses, which include dengue virus and West Nile virus.
Despite their medical importance, there are very few prophylactic or therapeutic
treatments for these viruses. Moreover, the manner in which they subvert the
innate immune response in order to establish infection in mammalian cells is not
well understood. Recently, peroxisomes were reported to function in early
antiviral signaling, but very little is known regarding if or how pathogenic
viruses affect these organelles. We report for the first time that flavivirus
infection results in significant loss of peroxisomes in mammalian cells, which
may indicate that targeting of peroxisomes is a key strategy used by viruses to
subvert early antiviral defenses.
PMID- 26423947
TI - AP-2 Is the Crucial Clathrin Adaptor Protein for CD4 Downmodulation by HIV-1 Nef
in Infected Primary CD4+ T Cells.
AB - HIV-1 Nef-mediated CD4 downmodulation involves various host factors. We
investigated the importance of AP-1, AP-2, AP-3, V1H-ATPase, beta-COP, and ACOT8
for CD4 downmodulation in HIV-1-infected short hairpin RNA (shRNA)-expressing
CD4(+) T cells and characterized direct interaction with Nef by Forster resonance
energy transfer (FRET). Binding of lentiviral Nefs to CD4 and AP-2 was conserved,
and only AP-2 knockdown impaired Nef-mediated CD4 downmodulation from primary T
cells. Altogether, among the factors tested, AP-2 is the most important player
for Nef-mediated CD4 downmodulation.
PMID- 26423948
TI - Differentiation-Coupled Induction of Human Cytomegalovirus Replication by Union
of the Major Enhancer Retinoic Acid, Cyclic AMP, and NF-kappaB Response Elements.
AB - Triggers and regulatory pathways that effectively link human cytomegalovirus
(HCMV) major immediate early (MIE) latent-lytic switch activation with progeny
production are incompletely understood. In the quiescently infected human NTera2
cell model of primitive neural stem cells, we found that costimulation with
vasoactive intestinal peptide (V) and phorbol ester (P) synergistically activated
viral infection, but this effect waned over time. Coupling retinoic acid (R), an
inducer of neuronal differentiation, to VP pulse stimulation attenuated the
decline in viral activity and promoted the spread of the active infection through
concentric layers of neighboring cells as cellular differentiation progressed. R
stimulation alone was unable to activate the infection. The MIE enhancer cis
regulatory mechanisms responsible for this result were characterized by a
strategy of combinatorial mutagenesis of five cis-acting element types (retinoic
acid receptor binding elements [RARE], cyclic AMP [cAMP] response elements [CRE],
NF-kappaB binding sites [kB], serum response element, and ETS/ELK-1 binding site)
and multiple methods of assessment. We found that the CRE and kB combination sets
the preinduction enhancer tone, is the major initiator and amplifier of RVP
induced MIE gene expression, and cooperates with RARE during cellular
differentiation to enhance viral spread. In predifferentiated NTera2, we also
found that the CRE-kB combination functions as initiator and amplifier of
unstimulated HCMV MIE gene expression and cooperatively interacts with RARE to
enhance viral spread. We conclude that RVP-stimulated signaling cascades and
cellular differentiation operate through the enhancer CRE-kB-RARE core in
strengthening induction of HCMV MIE gene expression in linkage with viral
propagation. IMPORTANCE: Cytomegalovirus-seropositive persons commonly lack
detectable levels of cytomegalovirus replication, even when profoundly
immunocompromised. In a human NTera2 cell model of primitive neural stem cells
carrying resting cytomegalovirus genomes, we show that costimulation of protein
kinase A and C-delta signaling cascades in conjunction with retinoic acid-induced
neuronal differentiation brings about progeny virus propagation. Iterated DNA
binding sites for retinoic acid receptor, CREB, and NF-kappaB family members in
the cytomegalovirus major enhancer are at the crux in the pathway to HCMV
activation. The stimulated CREB and NF-kappaB binding site combination vigorously
initiates and amplifies the active cytomegalovirus infection and cooperates with
activated retinoic acid receptor binding sites to further promote viral
proliferation and spread between differentiated cells. These results support a
paradigm in which a specific combination of stimuli coupled with cellular
differentiation satisfies a core cis-activating code that unlocks enhancer
silence to repower the cycle of cytomegalovirus propagation.
PMID- 26423949
TI - The Fusion Protein Specificity of the Parainfluenza Virus Hemagglutinin
Neuraminidase Protein Is Not Solely Defined by the Primary Structure of Its Stalk
Domain.
AB - Virus-specific interaction between the attachment protein (HN) and the fusion
protein (F) is prerequisite for the induction of membrane fusion by parainfluenza
viruses. This HN-F interaction presumably is mediated by particular amino acids
in the HN stalk domain and those in the F head domain. We found in the present
study, however, that a simian virus 41 (SV41) F-specific chimeric HPIV2 HN
protein, SCA, whose cytoplasmic, transmembrane, and stalk domains were derived
from the SV41 HN protein, could not induce cell-cell fusion of BHK-21 cells when
coexpressed with an SV41 HN-specific chimeric PIV5 F protein, no. 36. Similarly,
a headless form of the SV41 HN protein failed to induce fusion with chimera no.
36, whereas it was able to induce fusion with the SV41 F protein. Interestingly,
replacement of 13 amino acids of the SCA head domain, which are located at or
around the dimer interface of the head domain, with SV41 HN counterparts resulted
in a chimeric HN protein, SCA-RII, which induced fusion with chimera no. 36 but
not with the SV41 F protein. More interestingly, retroreplacement of 11 out of
the 13 amino acids of SCA-RII with the SCA counterparts resulted in another
chimeric HN protein, IM18, which induced fusion either with chimera no. 36 or
with the SV41 F protein, similar to the SV41 HN protein. Thus, we conclude that
the F protein specificity of the HN protein that is observed in the fusion event
is not solely defined by the primary structure of the HN stalk domain.
IMPORTANCE: It is appreciated that the HN head domain initially conceals the HN
stalk domain but exposes it after the head domain has bound to the receptors,
which allows particular amino acids in the stalk domain to interact with the F
protein and trigger it to induce fusion. However, other regulatory roles of the
HN head domain in the fusion event have been ill defined. We have shown in the
current study that removal of the head domain or amino acid substitutions in a
particular region of the head domain drastically change the F protein specificity
of the HN protein, suggesting that the ability of a given HN protein to interact
with an F protein is defined not only by the primary structure of the HN stalk
domain but also by its conformation. This notion seems to account for the
unidirectional substitutability among rubulavirus HN proteins in triggering
noncognate F proteins.
PMID- 26423950
TI - Deer Prion Proteins Modulate the Emergence and Adaptation of Chronic Wasting
Disease Strains.
AB - Transmission of chronic wasting disease (CWD) between cervids is influenced by
the primary structure of the host cellular prion protein (PrP(C)). In white
tailed deer, PRNP alleles encode the polymorphisms Q95 G96 (wild type [wt]), Q95
S96 (referred to as the S96 allele), and H95 G96 (referred to as the H95 allele),
which differentially impact CWD progression. We hypothesize that the transmission
of CWD prions between deer expressing different allotypes of PrP(C) modifies the
contagious agent affecting disease spread. To evaluate the transmission
properties of CWD prions derived experimentally from deer of four PRNP genotypes
(wt/wt, S96/wt, H95/wt, or H95/S96), transgenic (tg) mice expressing the wt
allele (tg33) or S96 allele (tg60) were challenged with these prion agents.
Passage of deer CWD prions into tg33 mice resulted in 100% attack rates, with the
CWD H95/S96 prions having significantly longer incubation periods. The disease
signs and neuropathological and protease-resistant prion protein (PrP-res)
profiles in infected tg33 mice were similar between groups, indicating that a
prion strain (Wisc-1) common to all CWD inocula was amplified. In contrast, tg60
mice developed prion disease only when inoculated with the H95/wt and H95/S96 CWD
allotypes. Serial passage in tg60 mice resulted in adaptation of a novel CWD
strain (H95(+)) with distinct biological properties. Transmission of first
passage tg60CWD-H95(+) isolates into tg33 mice, however, elicited two prion
disease presentations consistent with a mixture of strains associated with
different PrP-res glycotypes. Our data indicate that H95-PRNP heterozygous deer
accumulated two CWD strains whose emergence was dictated by the PrP(C) primary
structure of the recipient host. These findings suggest that CWD transmission
between cervids expressing distinct PrP(C) molecules results in the generation of
novel CWD strains. IMPORTANCE: CWD prions are contagious among wild and captive
cervids in North America and in South Korea. We present data linking the amino
acid variant Q95H in white-tailed deer cellular prion protein (PrP(C)) to the
emergence of a novel CWD strain (H95(+)). We show that, upon infection, deer
expressing H95-PrP(C) molecules accumulated a mixture of CWD strains that
selectively propagated depending on the PRNP genotype of the host in which they
were passaged. Our study also demonstrates that mice expressing the deer S96-PRNP
allele, previously shown to be resistant to various cervid prions, are
susceptible to H95(+) CWD prions. The potential for the generation of novel
strains raises the possibility of an expanded host range for CWD.
PMID- 26423951
TI - Comparison of the Life Cycles of Genetically Distant Species C and Species D
Human Adenoviruses Ad6 and Ad26 in Human Cells.
AB - Our understanding of adenovirus (Ad) biology is largely extrapolated from human
species C Ad5. Most humans are immune to Ad5, so lower-seroprevalence viruses
like human Ad6 and Ad26 are being tested as therapeutic vectors. Ad6 and Ad26
differ at the DNA level by 34%. To better understand how this might impact their
biology, we examined the life cycle of the two viruses in human lung cells in
vitro. Both viruses infected A549 cells with similar efficiencies, executed DNA
replication with identical kinetics within 12 h, and began killing cells within
72 h. While Ad6-infected cells remained adherent until death, Ad26-infected cells
detached within 12 h of infection but remained viable. Next-generation sequencing
(NGS) of mRNA from infected cells demonstrated that viral transcripts constituted
1% of cellular mRNAs within 6 h and 8 to 16% within 12 h. Quantitative PCR and
NGS revealed the activation of key early genes at 6 h and transition to late gene
activation by 12 h by both viruses. There were marked differences in the balance
of E1A and E1B activation by the two viruses and in the expression of E3 immune
evasion mRNAs. Ad6 was markedly more effective at suppressing major
histocompatibility complex class I (MHC I) display on the cell surface and in
evading TRAIL-mediated apoptosis than was Ad26. These data demonstrate shared as
well as divergent life cycles in these genetically distant human adenoviruses. An
understanding of these differences expands the knowledge of alternative Ad
species and may inform the selection of related Ads for therapeutic development.
IMPORTANCE: A burgeoning number of adenoviruses (Ads) are being harnessed as
therapeutics, yet the biology of these viruses is generally extrapolated from Ad2
and Ad5. Here, we are the first to compare the transcriptional programs of two
genetically distant Ads by mRNA next-generation sequencing (NGS). Species C Ad6
and Ad26 are being pursued as lower-seroprevalence Ad vectors but differ at the
DNA level by 34%. Head-to-head comparison in human lung cells by NGS revealed
that the two viruses generally conform to our general understanding of the Ad
transcriptional program. However, fine mapping revealed subtle and strong
differences in how these two viruses execute these programs, including
differences in the balance of E1A and E1B mRNAs and in E3 immune evasion genes.
This suggests that not all adenoviruses behave like Ad2 and Ad5 and that they may
have unique strategies to infect cells and evade the immune system.
PMID- 26423952
TI - Whole-Genome Sequencing of Kaposi's Sarcoma-Associated Herpesvirus from Zambian
Kaposi's Sarcoma Biopsy Specimens Reveals Unique Viral Diversity.
AB - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent for
Kaposi's sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where
approximately 84% of global KS cases occur. Nevertheless, whole-genome sequencing
of KSHV has only been completed using isolates from Western countries-where KS is
not endemic. The lack of whole-genome KSHV sequence data from the most clinically
important geographical region, sub-Saharan Africa, represents an important gap
since it remains unclear whether genomic diversity has a role on KSHV
pathogenesis. We hypothesized that distinct KSHV genotypes might be present in
sub-Saharan Africa compared to Western countries. Using a KSHV-targeted
enrichment protocol followed by Illumina deep-sequencing, we generated and
analyzed 16 unique Zambian, KS-derived, KSHV genomes. We enriched KSHV DNA over
cellular DNA 1,851 to 18,235-fold. Enrichment provided coverage levels up to
24,740-fold; therefore, supporting highly confident polymorphism analysis.
Multiple alignment of the 16 newly sequenced KSHV genomes showed low level
variability across the entire central conserved region. This variability resulted
in distinct phylogenetic clustering between Zambian KSHV genomic sequences and
those derived from Western countries. Importantly, the phylogenetic segregation
of Zambian from Western sequences occurred irrespective of inclusion of the
highly variable genes K1 and K15. We also show that four genes within the more
conserved region of the KSHV genome contained polymorphisms that partially, but
not fully, contributed to the unique Zambian KSHV whole-genome phylogenetic
structure. Taken together, our data suggest that the whole KSHV genome should be
taken into consideration for accurate viral characterization. IMPORTANCE: Our
results represent the largest number of KSHV whole-genomic sequences published to
date and the first time that multiple genomes have been sequenced from sub
Saharan Africa, a geographic area where KS is highly endemic. Based on our new
sequence data, it is apparent that whole-genome KSHV diversity is greater than
previously appreciated and differential phylogenetic clustering exists between
viral genomes of Zambia and Western countries. Furthermore, individual genes may
be insufficient for KSHV genetic characterization. Continued investigation of the
KSHV genetic landscape is necessary in order to effectively understand the role
of viral evolution and sequence diversity on KSHV gene functions and
pathogenesis.
PMID- 26423953
TI - Breakthrough Virus Neutralization Resistance as a Correlate of Protection in a
Nonhuman Primate Heterologous Simian Immunodeficiency Virus Vaccine Challenge
Study.
AB - Comprehensive assessments of immune correlates of protection in human
immunodeficiency virus (HIV) vaccine trials are essential to vaccine design.
Neutralization sieve analysis compares the neutralization sensitivity of the
breakthrough transmitted/founder (TF) viruses from vaccinated and control animals
to infer the molecular mechanisms of vaccine protection. Here, we report a robust
neutralization sieve effect in a nonhuman primate simian immunodeficiency virus
(SIV) vaccine trial (DNA prime/recombinant adenovirus type 5 [rAd5] boost) (VRC
10-332) that demonstrated substantial protective efficacy and revealed a genetic
signature of neutralization resistance in the C1 region of env. We found
significant enrichment for neutralization resistance in the vaccine compared to
control breakthrough TF viruses when tested with plasma from vaccinated study
animals, plasma from chronically SIV-infected animals, and a panel of SIV
specific monoclonal antibodies targeting six discrete Env epitopes (P < 0.008 for
all comparisons). Neutralization resistance was significantly associated with the
previously identified genetic signature of resistance (P < 0.0001), and together,
the results identify virus neutralization as a correlate of protection. These
findings further demonstrate the in vivo relevance of our previous in vitro
analyses of the SIVsmE660 challenge stock, which revealed a broad range of
neutralization sensitivities of its component viruses. In sum, this report
demonstrates proof-of-concept that phenotypic sieve analyses can elucidate
mechanistic correlates of immune protection following vaccination and raises a
cautionary note for SIV and SHIV (simian-human immunodeficiency virus) vaccine
studies that employ challenge strains with envelope glycoproteins that fail to
exhibit neutralization resistance profiles typical of TF viruses. IMPORTANCE:
With more than 2 million new infections annually, the development of an effective
vaccine against HIV-1 is a global health priority. Understanding immunologic
correlates of protection generated in vaccine trials is critical to advance
vaccine development. Here, we assessed the role of vaccine-elicited neutralizing
antibodies in a recent nonhuman primate study of a vaccine that showed
significant protection against simian immunodeficiency virus (SIV) challenge and
suggested a genetic signature of neutralization sensitivity. We found that
breakthrough viruses able to establish infection in vaccinated animals were
substantially more resistant to antibody-mediated neutralization than were
viruses from controls. These findings suggest that vaccine-elicited neutralizing
antibodies selectively blocked the transmission of more sensitive challenge
viruses. Sieve analysis also corroborated a genetic signature of neutralization
sensitivity and highlighted the impact of challenge swarm diversity. Our findings
suggest an important role for neutralization sieve analyses as an informative
component of comprehensive immune-correlates analyses.
PMID- 26423954
TI - A Unique 5' Translation Element Discovered in Triticum Mosaic Virus.
AB - Several plant viruses encode elements at the 5' end of their RNAs, which, unlike
most cellular mRNAs, can initiate translation in the absence of a 5' m7GpppG cap.
Here, we describe an exceptionally long (739-nucleotide [nt]) leader sequence in
triticum mosaic virus (TriMV), a recently emerged wheat pathogen that belongs to
the Potyviridae family of positive-strand RNA viruses. We demonstrate that the
TriMV 5' leader drives strong cap-independent translation in both wheat germ
extract and oat protoplasts through a novel, noncanonical translation mechanism.
Translation preferentially initiates at the 13th start codon within the leader
sequence independently of eIF4E but involves eIF4G. We truncated the 5' leader to
a 300-nucleotide sequence that drives cap-independent translation from the 5'
end. We show that within this sequence, translation activity relies on a stem
loop structure identified at nucleotide positions 469 to 490. The disruption of
the stem significantly impairs the function of the 5' untranslated region (UTR)
in driving translation and competing against a capped RNA. Additionally, the
TriMV 5' UTR can direct translation from an internal position of a bicistronic
mRNA, and unlike cap-driven translation, it is unimpaired when the 5' end is
blocked by a strong hairpin in a monocistronic reporter. However, the disruption
of the identified stem structure eliminates such a translational advantage. Our
results reveal a potent and uniquely controlled translation enhancer that may
provide new insights into mechanisms of plant virus translational regulation.
IMPORTANCE: Many members of the Potyviridae family rely on their 5' end for
translation. Here, we show that the 739-nucleotide-long triticum mosaic virus 5'
leader bears a powerful translation element with features distinct from those
described for other plant viruses. Despite the presence of 12 AUG start codons
within the TriMV 5' UTR, translation initiates primarily at the 13th AUG codon.
The TriMV 5' UTR is capable of driving cap-independent translation in vitro and
in vivo, is independent of eIF4E, and can drive internal translation initiation.
A hairpin structure at nucleotide positions 469 to 490 is required for the cap
independent translation and internal translation initiation abilities of the
element and plays a role in the ability of the TriMV UTR to compete against a
capped RNA in vitro. Our results reveal a novel translation enhancer that may
provide new insights into the large diversity of plant virus translation
mechanisms.
PMID- 26423955
TI - Ultrastructural Characterization of Turnip Mosaic Virus-Induced Cellular
Rearrangements Reveals Membrane-Bound Viral Particles Accumulating in Vacuoles.
AB - Positive-strand RNA [(+) RNA] viruses remodel cellular membranes to facilitate
virus replication and assembly. In the case of turnip mosaic virus (TuMV), the
viral membrane protein 6K2 plays an essential role in endomembrane alterations.
Although 6K2-induced membrane dynamics have been widely studied by confocal
microscopy, the ultrastructure of this remodeling has not been extensively
examined. In this study, we investigated the formation of TuMV-induced membrane
changes by chemical fixation and high-pressure freezing/freeze substitution
(HPF/FS) for transmission electron microscopy at different times of infection. We
observed the formation of convoluted membranes connected to rough endoplasmic
reticulum (rER) early in the infection process, followed by the production of
single-membrane vesicle-like (SMVL) structures at the midstage of infection. Both
SMVL and double-membrane vesicle-like structures with electron-dense cores, as
well as electron-dense bodies, were found late in the infection process.
Immunogold labeling results showed that the vesicle-like structures were 6K2
tagged and suggested that only the SMVL structures were viral RNA replication
sites. Electron tomography (ET) was used to regenerate a three-dimensional model
of these vesicle-like structures, which showed that they were, in fact, tubules.
Late in infection, we observed filamentous particle bundles associated with
electron-dense bodies, which suggests that these are sites for viral particle
assembly. In addition, TuMV particles were observed to accumulate in the central
vacuole as membrane-associated linear arrays. Our work thus unravels the
sequential appearance of distinct TuMV-induced membrane structures for viral RNA
replication, viral particle assembly, and accumulation. IMPORTANCE: Positive
strand RNA viruses remodel cellular membranes for different stages of the
infection process, such as protein translation and processing, viral RNA
synthesis, particle assembly, and virus transmission. The ultrastructure of
turnip mosaic virus (TuMV)-induced membrane remodeling was investigated over
several days of infection. The first change that was observed involved
endoplasmic reticulum-connected convoluted membrane accumulation. This was
followed by the formation of single-membrane tubules, which were shown to be
viral RNA replication sites. Later in the infection process, double-membrane
tubular structures were observed and were associated with viral particle bundles.
In addition, TuMV particles were observed to accumulate in the central vacuole as
membrane-associated linear arrays. This work thus unravels the sequential
appearance of distinct TuMV-induced membrane structures for viral RNA
replication, viral particle assembly, and accumulation.
PMID- 26423956
TI - An RNA Domain Imparts Specificity and Selectivity to a Viral DNA Packaging Motor.
AB - During assembly, double-stranded DNA viruses, including bacteriophages and
herpesviruses, utilize a powerful molecular motor to package their genomic DNA
into a preformed viral capsid. An integral component of the packaging motor in
the Bacillus subtilis bacteriophage phi29 is a viral genome-encoded pentameric
ring of RNA (prohead RNA [pRNA]). pRNA is a 174-base transcript comprised of two
domains, domains I and II. Early studies initially isolated a 120-base form
(domain I only) that retains high biological activity in vitro; hence, no
function could be assigned to domain II. Here we define a role for this domain in
the packaging process. DNA packaging using restriction digests of phi29 DNA
showed that motors with the 174-base pRNA supported the correct polarity of DNA
packaging, selectively packaging the DNA left end. In contrast, motors containing
the 120-base pRNA had compromised specificity, packaging both left- and right-end
fragments. The presence of domain II also provides selectivity in competition
assays with genomes from related phages. Furthermore, motors with the 174-base
pRNA were restrictive, in that they packaged only one DNA fragment into the head,
whereas motors with the 120-base pRNA packaged several fragments into the head,
indicating multiple initiation events. These results show that domain II imparts
specificity and stringency to the motor during the packaging initiation events
that precede DNA translocation. Heteromeric rings of pRNA demonstrated that one
or two copies of domain II were sufficient to impart this selectivity/stringency.
Although phi29 differs from other double-stranded DNA phages in having an RNA
motor component, the function provided by pRNA is carried on the motor protein
components in other phages. IMPORTANCE: During virus assembly, genome packaging
involves the delivery of newly synthesized viral nucleic acid into a protein
shell. In the double-stranded DNA phages and herpesviruses, this is accomplished
by a powerful molecular motor that translocates the viral DNA into a preformed
viral shell. A key event in DNA packaging is recognition of the viral DNA among
other nucleic acids in the host cell. Commonly, a DNA-binding protein mediates
the interaction of viral DNA with the motor/head shell. Here we show that for the
bacteriophage phi29, this essential step of genome recognition is mediated by a
viral genome-encoded RNA rather than a protein. A domain of the prohead RNA
(pRNA) imparts specificity and stringency to the motor by ensuring the correct
orientation of DNA packaging and restricting initiation to a single event. Since
this assembly step is unique to the virus, DNA packaging is a novel target for
the development of antiviral drugs.
PMID- 26423957
TI - Prion Infectivity Plateaus and Conversion to Symptomatic Disease Originate from
Falling Precursor Levels and Increased Levels of Oligomeric PrPSc Species.
AB - In lethal prion neurodegenerative diseases, misfolded prion proteins (PrP(Sc))
replicate by redirecting the folding of the cellular prion glycoprotein (PrP(C)).
Infections of different durations can have a subclinical phase with constant
levels of infectious particles, but the mechanisms underlying this plateau and a
subsequent exit to overt clinical disease are unknown. Using tandem biophysical
techniques, we show that attenuated accumulation of infectious particles in
presymptomatic disease is preceded by a progressive fall in PrP(C) level, which
constricts replication rate and thereby causes the plateau effect. Furthermore,
disease symptoms occurred at the threshold associated with increasing levels of
small, relatively less protease-resistant oligomeric prion particles (oPrP(Sc)).
Although a hypothetical lethal isoform of PrP cannot be excluded, our data argue
that diminishing residual PrP(C) levels and continuously increasing levels of
oPrP(Sc) are crucial determinants in the transition from presymptomatic to
symptomatic prion disease. IMPORTANCE: Prions are infectious agents that cause
lethal brain diseases; they arise from misfolding of a cell surface protein,
PrP(C) to a form called PrP(Sc). Prion infections can have long latencies even
though there is no protective immune response. Accumulation of infectious prion
particles has been suggested to always reach the same plateau in the brain during
latent periods, with clinical disease only occurring when hypothetical toxic
forms (called PrP(L) or TPrP) begin to accumulate. We show here that infectivity
plateaus arise because PrP(C) precursor levels become downregulated and that the
duration of latent periods can be accounted for by the level of residual PrP(C),
which transduces a toxic effect, along with the amount of oligomeric forms of
PrP(Sc).
PMID- 26423958
TI - Erianthus arundinaceus HSP70 (EaHSP70) Acts as a Key Regulator in the Formation
of Anisotropic Interdigitation in Sugarcane (Saccharum spp. hybrid) in Response
to Drought Stress.
AB - Plant growth during abiotic stress is a long sought-after trait especially in
crop plants in the context of global warming and climate change. Previous studies
on leaf epidermal cells have revealed that during normal growth and development,
adjacent cells interdigitate anisotropically to form cell morphological patterns
known as interlocking marginal lobes (IMLs), involving the cell wall-cell
membrane-cortical actin continuum. IMLs are growth-associated cell morphological
changes in which auxin-binding protein (ABP), Rho GTPases and actin are known to
play important roles. In the present study, we investigated the formation of IMLs
under drought stress and found that Erianthus arundinaceus, a drought-tolerant
wild relative of sugarcane, develops such growth-related cell morphological
patterns under drought stress. Using confocal microscopy, we showed an increasing
trend in cortical F-actin intensity in drought-tolerant plants with increasing
soil moisture stress. In order to check the role of drought tolerance-related
genes in IML formation under soil moisture stress, we adopted a structural data
mining strategy and identified indirect connections between the ABPs and heat
shock proteins (HSPs). Initial experimental evidence for this connection comes
from the high transcript levels of HSP70 observed in drought-stressed Erianthus,
which developed anisotropic interdigitation, i.e. IMLs. Subsequently, by
overexpressing the E. arundinaceus HSP70 gene (EaHSP70) in sugarcane (Saccharum
spp. hybrid), we confirm the role of HSP70 in the formation of anisotropic
interdigitation under drought stress. Taken together, our results suggest that
EaHSP70 acts as a key regulator in the formation of anisotropic interdigitation
in drought-tolerant plants (Erianthus and HSP70 transgenic sugarcane) under
moisture stress in an actin-mediated pathway. The possible biological
significance of the formation of drought-associated interlocking marginal lobes
(DaIMLs) in sugarcane plants upon drought stress is discussed.
PMID- 26423959
TI - Arabidopsis INCURVATA2 Regulates Salicylic Acid and Abscisic Acid Signaling, and
Oxidative Stress Responses.
AB - Epigenetic regulatory states can persist through mitosis and meiosis, but the
connection between chromatin structure and DNA replication remains unclear.
Arabidopsis INCURVATA2 (ICU2) encodes the catalytic subunit of DNA polymerase
alpha, and null alleles of ICU2 have an embryo-lethal phenotype. Analysis of icu2
1, a hypomorphic allele of ICU2, demonstrated that ICU2 functions in chromatin
mediated cellular memory; icu2-1 strongly impairs ICU2 function in the
maintenance of repressive epigenetic marks but does not seem to affect ICU2
polymerase activity. To better understand the global function of ICU2 in
epigenetic regulation, here we performed a microarray analysis of icu2-1 mutant
plants. We found that the genes up-regulated in the icu2-1 mutant included genes
encoding transcription factors and targets of the Polycomb Repressive Complexes.
The down-regulated genes included many known players in salicylic acid (SA)
biosynthesis and accumulation, ABA signaling and ABA-mediated responses. In
addition, we found that icu2-1 plants had reduced SA levels in normal conditions;
infection by Fusarium oxysporum induced SA accumulation in the En-2 wild type but
not in the icu2-1 mutant. The icu2-1 plants were also hypersensitive to salt
stress and exogenous ABA in seedling establishment, post-germination growth and
stomatal closure, and accumulated more ABA than the wild type in response to salt
stress. The icu2-1 mutant also showed high tolerance to the oxidative stress
produced by 3-amino-1,2,4-triazole (3-AT). Our results uncover a role for ICU2 in
the regulation of genes involved in ABA signaling as well as in SA biosynthesis
and accumulation.
PMID- 26423960
TI - The C-Terminal Sequence and PI motif of the Orchid (Oncidium Gower Ramsey)
PISTILLATA (PI) Ortholog Determine its Ability to Bind AP3 Orthologs and Enter
the Nucleus to Regulate Downstream Genes Controlling Petal and Stamen Formation.
AB - This study focused on the investigation of the effects of the PI motif and C
terminus of the Oncidium Gower Ramsey MADS box gene 8 (OMADS8), a PISTILLATA (PI)
ortholog, on floral organ formation. 35S::OMADS8 completely rescued and
35S::OMADS8-PI (with the PI motif deleted) partially rescued petal/stamen
formation, whereas these deficiencies were not rescued by 35S::OMADS8-C (C
terminal 29 amino acids deleted) in pi-1 mutants. OMADS8 could interact with
Arabidopsis APETALA3 (AP3) and enter the nucleus. The nuclear entry efficiency
was reduced for OMADS8-PI/AP3 and OMADS8-C/AP3. OMADS8 could also interact with
OMADS5/OMADS9 (the Oncidium AP3 ortholog) and enter the nucleus with an
efficiency only slightly affected by the deletion of the C-terminal sequence or
PI motif. However, the stability of the OMADS8/OMADS5 and OMADS8/OMADS9 complexes
was significantly reduced by deletion of the C-terminal sequence or PI motif.
Further analysis indicated that the expression of genes downstream of AP3/PI
(BNQ1/BNQ2/GNC/At4g30270) was compensated by 35S::OMADS8 and 35S::OMADS8-PI to a
level similar to wild-type plants but was not affected by 35S::OMADS8-C in the pi
1 mutants. A similar FRET (fluorescence resonance energy transfer) efficiency was
observed for Arabidopsis AGAMOUS (AG) and the Oncidium AG ortholog OMADS4 for
OMADS8, OMADS8-PI and OMADS8-C. These results indicated that the OMADS8 PI motif
and C-terminus were valuable for the interaction of OMADS8 with the AP3 orthologs
to form higher order heterotetrameric complexes that regulated petal/stamen
formation in both Oncidium orchids and transgenic Arabidopsis. However, the C
terminal sequence and PI motif were dispensable for the interaction of OMADS8
with the AG orthologs.
PMID- 26423961
TI - Effects of Elevated Atmospheric CO2 on Primary Metabolite Levels in Arabidopsis
thaliana Col-0 Leaves: An Examination of Metabolome Data.
AB - Elevated atmospheric CO(2) concentrations ([CO(2)]) affect primary metabolite
levels because CO(2) is a direct substrate for photosynthesis. In several
studies, the responses of primary metabolite levels have been examined using
Arabidopsis thaliana leaves, but these results have not been comprehensively
discussed. Here, we examined metabolome data for A. thaliana accession Col-0
leaves that were grown at elevated [CO(2)] with sufficient nitrogen (N)
nutrition. At elevated [CO(2)], starch, monosaccharides and several major amino
acids accumulated in leaves. The degree of accumulation depended on whether the
rooting medium contained NH(4) (+) or only NO(3) (-). Because low N conditions
induce an increase in carbohydrates similar to that of elevated [CO(2)], we
compared the responses of primary metabolite levels between elevated [CO(2)] and
low N conditions. Levels of the tricarboxylic acid (TCA) cycle-associated organic
acids and major amino acids decreased with low N, but not with elevated [CO(2)].
Even at elevated [CO(2)], the low N induced the decreases in the levels of
organic acids and major amino acids. A small sink size also affects the primary
metabolite response patterns in leaves under elevated [CO(2)] conditions. Thus,
care is necessary when interpreting primary metabolite changes in leaves of field
grown plants.
PMID- 26423962
TI - Neuroprotective Effect of Calpeptin on Acrylamide-Induced Neuropathy in Rats.
AB - Acrylamide (ACR) is a vinyl monomer with established human neurotoxic effects,
which is characterized by the accumulation of neurofilaments (NFs) in the distal
swellings of large axons in peripheral and central nervous systems. However, the
mechanisms of neurotoxicity remain unclear. The objective is to investigate the
neuroprotective effect of calpeptin (CP) on ACR-induced neuropathy and its
mechanism. Female adult Wistar rats were randomly divided into four groups
(control, CP, ACR, and ACR + CP group). Control group received 0.9 % saline, ACR
and ACR + CP groups received 30 mg/kg ACR by intraperitoneal injection. In
addition, CP and ACR + CP groups also received 200 ug/kg CP. Gait analysis and
hind limb splay were measured weekly to analyze neurobehavioral changes. The
calpain activity and the changes of NFs protein levels in spinal cord are
determined. Compared with control group, body weight of rats in ACR group
decreased by 11.3 % (P < 0.01), while in ACR + CP group body weight increased
significantly by 8.3 % (P < 0.01) compared with ACR group by the end of the 4th
week; gait score of rats in both ACR and ACR + CP groups increased significantly
by 167 % and 100 % (P < 0.01) compared with control group, while it decreased
significantly by 25.1 % (P < 0.01) in ACR + CP group compared with ACR group; the
distance of hind limb splay in both ACR and ACR + CP groups increased by 76.7 %
and 49.5 % (P < 0.01) compared with control group, while it decreased by 15.4 %
(P < 0.01) in ACR + CP group compared with ACR group; calpain activity of spinal
cord at ACR and ACR + CP groups increased significantly by 14.9 % and 10.0 % (P <
0.01) compared with control group, while it decreased 4.2 % (P < 0.01) in ACR +
CP group compared with ACR group; compared with control group, the levels of
light NF (NF-L), medium NF (NF-M) and heavy NF (NF-H) subunits increased by 81.2
%, 263.6 % and 22.6 % (P < 0.01) in the supernatant of ACR group in spinal cord
tissue and increased by 28.4 %, 96.6 % and 10.6 % (P < 0.01) in ACR + CP group,
while the levels of NF-L, NF-M and NF-H subunits decreased by 29.1 %, 45.9 % and
9.8 % (P < 0.01) in ACR + CP group compared with ACR group. The present results
suggested that CP can relieve ACR neuropathy by decrease calpain activity and NFs
degradation. The changes of calpain activity and NFs may be one of the mechanisms
of ACR-induced neuropathy.
PMID- 26423963
TI - Library Construction for Mutation Identification by Whole-Genome Sequencing.
AB - Next-generation sequencing provides a rapid and powerful method for mutation
identification. Herein is described a workflow for sample preparation to allow
the simultaneous mapping and identification of candidate mutations by whole
genome sequencing in Caenorhabditis elegans. The protocol is designed for small
numbers of worms to accommodate classes of mutations, such as lethal and sterile
alleles, that are difficult to identify by traditional means.
PMID- 26423964
TI - Fundamentals of Comparative Genome Analysis in Caenorhabditis Nematodes.
AB - The genome of the nematode Caenorhabditis elegans was the first of any animal to
be sequenced completely, and it remains the "gold standard" for completeness and
annotations. Even before the C. elegans genome was completed, however, biologists
began examining the generality of its features in the genomes of other
Caenorhabditis species. With many such genomes now sequenced and available via
WormBase, C. elegans researchers are often confronted with how to interpret
comparative genomic data. In this article, we present practical approaches to
addressing several common issues, including possible sources of error in homology
annotations, the often complex relationships between sequence similarity,
orthology, paralogy, and gene family evolution, the impact of sexual mode on
genome assemblies and content, and the determination and use of synteny as a
tool.
PMID- 26423965
TI - Genetic Methods for Cellular Manipulations in C. elegans.
AB - Neuron manipulation in vivo by ablation, activation, or inactivation, and
regulation of gene expression, is essential for dissecting nervous system
function. Here we describe genetic means for neuron manipulation in the nematode
C. elegans, and provide protocols for generating transgenic animals containing
these genetic tools.
PMID- 26423966
TI - A Fusion PCR Method for Expressing Genetic Tools in C. elegans.
AB - C. elegans offer a unique opportunity for understanding computation in neural
networks. This is largely due to their relatively compact neural network for
which a wiring diagram is available. Recent advances in genetic tools for
interrogating neural activity (e.g., optogenetics) make C. elegans particularly
compelling as they can be expressed in many different combinations in target
individual neurons. Thus, the prospect to decipher principles underlying
functionality in neural networks largely depends on the ease by which transgenic
animals can be generated. Traditionally, to generate transgenic animals one would
inject a plasmid containing the gene of interest under the regulation of the cell
or lineage-specific promoter. This often requires laborious cloning steps of
both the gene and the promoter. The Hobert lab has developed a simpler protocol
in which linear PCR fragments can be injected to generate transgenic animals.
Relying on this PCR fusion-based method, here we provide a detailed protocol that
we have optimized for expressing various genetically encoded calcium indicators
and optogenetic tools in individual or sets of neurons. We use these simple
procedures to generate multiple constructs within a very short time frame
(typically 1-2 days).
PMID- 26423967
TI - Transposon-Assisted Genetic Engineering with Mos1-Mediated Single-Copy Insertion
(MosSCI).
AB - Transgenesis in model organisms is necessary to determine the function,
expression, and subcellular localization of gene products. In Caenorhabditis
elegans, injected DNA can be propagated as multicopy extrachromosomal arrays but
transgenes in arrays are mosaic, over-expressed in some tissues and silenced in
the germline. Here, a method to insert a transgene into a specific genomic
location called Mos1-mediated single-copy insertion (MosSCI) is described. Single
copy insertion allows transgene expression at levels that approximate endogenous
gene expression as well as expression in the germline.
PMID- 26423968
TI - Creating Genome Modifications in C. elegans Using the CRISPR/Cas9 System.
AB - The clustered, regularly interspaced, short, palindromic repeat (CRISPR)
associated (CAS) nuclease Cas9 has been used in many organisms to generate
specific mutations and transgene insertions. Here we describe a method using the
S. pyogenes Cas9 in C. elegans that provides a convenient and effective approach
for making heritable changes to the worm genome.
PMID- 26423969
TI - Observing and Quantifying Fluorescent Reporters.
AB - Genetically encoded fluorescent reporters take advantage of C. elegans'
transparency to allow noninvasive, in vivo observation and recording of
physiological processes in intact animals. Here, I discuss the basic microscope
components required to observe, image, and measure fluorescent proteins in live
animals for students and researchers who work with C. elegans but have limited
experience with fluorescence imaging and analysis.
PMID- 26423970
TI - Microbial Rhodopsin Optogenetic Tools: Application for Analyses of Synaptic
Transmission and of Neuronal Network Activity in Behavior.
AB - Optogenetics was introduced as a new technology in the neurosciences about a
decade ago (Zemelman et al., Neuron 33:15-22, 2002; Boyden et al., Nat Neurosci
8:1263-1268, 2005; Nagel et al., Curr Biol 15:2279-2284, 2005; Zemelman et al.,
Proc Natl Acad Sci USA 100:1352-1357, 2003). It combines optics, genetics, and
bioengineering to render neurons sensitive to light, in order to achieve a
precise, exogenous, and noninvasive control of membrane potential, intracellular
signaling, network activity, or behavior (Rein and Deussing, Mol Genet Genomics
287:95-109, 2012; Yizhar et al., Neuron 71:9-34, 2011). As C. elegans is
transparent, genetically amenable, has a small nervous system mapped with synapse
resolution, and exhibits a rich behavioral repertoire, it is especially open to
optogenetic methods (White et al., Philos Trans R Soc Lond B Biol Sci 314:1-340,
1986; De Bono et al., Optogenetic actuation, inhibition, modulation and readout
for neuronal networks generating behavior in the nematode Caenorhabditis elegans,
In: Hegemann P, Sigrist SJ (eds) Optogenetics, De Gruyter, Berlin, 2013; Husson
et al., Biol Cell 105:235-250, 2013; Xu and Kim, Nat Rev Genet 12:793-801, 2011).
Optogenetics, by now an "exploding" field, comprises a repertoire of different
tools ranging from transgenically expressed photo-sensor proteins (Boyden et al.,
Nat Neurosci 8:1263-1268, 2005; Nagel et al., Curr Biol 15:2279-2284, 2005) or
cascades (Zemelman et al., Neuron 33:15-22, 2002) to chemical biology approaches,
using photochromic ligands of endogenous channels (Szobota et al., Neuron 54:535
545, 2007). Here, we will focus only on optogenetics utilizing microbial
rhodopsins, as these are most easily and most widely applied in C. elegans. For
other optogenetic tools, for example the photoactivated adenylyl cyclases (PACs,
that drive neuronal activity by increasing synaptic vesicle priming, thus
exaggerating rather than overriding the intrinsic activity of a neuron, as occurs
with rhodopsins), we refer to other literature (Weissenberger et al., J Neurochem
116:616-625, 2011; Steuer Costa et al., Photoactivated adenylyl cyclases as
optogenetic modulators of neuronal activity, In: Cambridge S (ed) Photswitching
proteins, Springer, New York, 2014). In this chapter, we will give an overview of
rhodopsin-based optogenetic tools, their properties and function, as well as
their combination with genetically encoded indicators of neuronal activity. As
there is not "the" single optogenetic experiment we could describe here, we will
focus more on general concepts and "dos and don'ts" when designing an optogenetic
experiment. We will also give some guidelines on which hardware to use, and then
describe a typical example of an optogenetic experiment to analyze the function
of the neuromuscular junction, and another application, which is Ca(2+) imaging
in body wall muscle, with upstream neuronal excitation using optogenetic
stimulation. To obtain a more general overview of optogenetics and optogenetic
tools, we refer the reader to an extensive collection of review articles, and in
particular to volume 1148 of this book series, "Photoswitching Proteins."
PMID- 26423972
TI - High-Pressure Freeze and Freeze Substitution Electron Microscopy in C. elegans.
AB - While traditional chemical fixation methods for C. elegans electron microscopy
(EM) have provided invaluable anatomical and structural information, the
development of high-pressure freeze (HPF) and freeze substitution (FS) protocols
offers advantages for high-resolution imaging. Specimens prepared using HPF
methodology exhibit fewer distortion artifacts due to fixation and dehydration,
have improved antigenicity, and result in a more physiologically accurate
structural representation of the worm. In the HPF technique, freely moving worms
are frozen at high-pressure (2100 bar) and low temperature (-180 degrees C)
within milliseconds. These conditions prevent the formation of ice crystals that
can damage cellular structures. Samples then undergo FS, during which worms are
slowly brought to room temperature while substituting amorphous ice with organic
solvents to preserve tissue in its near native state and provide contrast for
imaging. FS can be performed in an automatic freeze substitution (AFS) machine or
in makeshift, temperature controlled chambers. Fixed worms can be embedded in
plastic resin and further processed for a variety of imaging techniques. Samples
then viewed using scanning (SEM) or transmission electron microscopy (TEM) will
show enhanced preservation of organelles, cell morphology, and antigenicity for
immunocytochemistry.
PMID- 26423971
TI - Simultaneous Optogenetic Stimulation of Individual Pharyngeal Neurons and
Monitoring of Feeding Behavior in Intact C. elegans.
AB - Optogenetic approaches have proven powerful for examining the role of neural
circuits in generating behaviors, especially in systems where
electrophysiological manipulation is not possible. Here we describe a method for
optogenetically manipulating single pharyngeal neurons in intact C. elegans while
monitoring pharyngeal behavior. This approach provides bidirectional and dynamic
control of pharyngeal neural activity simultaneously with a behavioral readout
and has allowed us to test hypotheses about the roles of individual pharyngeal
neurons in regulating feeding behavior.
PMID- 26423973
TI - Electron Tomography Methods for C. elegans.
AB - Methods for electron tomography of the nematode C. elegans are explained in
detail, including a brief introduction to specimen preparation, methods for image
collection, and a comparison of several general methods for producing dual-axis
tomograms, with or without external fiducial reference objects. New electron
tomograms highlight features in software for data display, annotation, and
analysis. This chapter discusses the ultrastructural analysis of cells and
tissues, rather than molecular studies.
PMID- 26423974
TI - Microfluidic Devices for Behavioral Analysis, Microscopy, and Neuronal Imaging in
Caenorhabditis elegans.
AB - Microfluidic devices offer several advantages for C. elegans research,
particularly for presenting precise physical and chemical environments,
immobilizing animals during imaging, quantifying behavior, and automating
screens. However, challenges to their widespread adoption in the field include
increased complexity over conventional methods, operational problems (such as
clogging, leaks, and bubbles), difficulty in obtaining or fabricating devices,
and the need to characterize biological results obtained from new assay formats.
Here we describe the preparation and operation of simple, reusable microfluidic
devices for quantifying behavioral responses to chemical patterns, and single-use
devices to arrange animals for time-lapse microscopy and to measure neuronal
activity. We focus on details that eliminate or reduce the frustrations commonly
experienced by new users of microfluidic devices.
PMID- 26423975
TI - Tracking Single C. elegans Using a USB Microscope on a Motorized Stage.
AB - Locomotion and gross morphology have been important phenotypes for C. elegans
genetics since the inception of the field and remain relevant. In parallel with
developments in genome sequencing and editing, phenotyping methods have become
more automated and quantitative, making it possible to detect subtle differences
between mutants and wild-type animals. In this chapter, we describe how to
calibrate a single-worm tracker consisting of a USB microscope mounted on a
motorized stage and how to record and analyze movies of worms crawling on food.
The resulting quantitative phenotypic fingerprint can sensitively identify
differences between mutant and wild-type worms.
PMID- 26423976
TI - An Imaging System for C. elegans Behavior.
AB - Many experiments in C. elegans neurobiology and development benefit from
automated imaging of worm behavior. Here we describe procedures for building a
flexible and inexpensive imaging system using standard optical and mechanical
components.
PMID- 26423977
TI - A Method for Obtaining Large Populations of Synchronized Caenorhabditis elegans
Dauer Larvae.
AB - The C. elegans dauer is an attractive model with which to investigate fundamental
biological questions, such as how environmental cues are sensed and are
translated into developmental decisions through a series of signaling cascades
that ultimately result in a transformed animal. Here we describe a simple method
of using egg white plates to obtain highly synchronized purified dauers that can
be used in downstream applications requiring large quantities of dauers or
postdauer animals.
PMID- 26423978
TI - Sampling and Isolation of C. elegans from the Natural Habitat.
AB - Wild populations of the model organism C. elegans allow characterization of
natural genetic variation underlying diverse phenotypic traits. Here we provide a
simple protocol on how to sample and rapidly identify C. elegans wild isolates.
We outline how to find suitable habitats and organic substrates, followed by
describing isolation and identification of C. elegans live cultures based on
easily recognizable morphological characteristics, molecular barcodes and/or
mating tests. This protocol uses standard laboratory equipment and requires no
prior knowledge of C. elegans biology.
PMID- 26423979
TI - A Primer on Prototyping.
AB - Standard mechanical components, such as adapters or mounts, are ubiquitous in
research laboratories, C. elegans labs included. Recently, in-house prototyping
and fabricating both standard and custom mechanical parts has become simple and
cost effective. Here we describe the basic steps, equipment, and considerations
required for rapid prototyping of a handful of simple yet useful designs. These
examples were chosen for their simplicity, as well as for demonstrating specific
practicalities. They are thus appropriate as training exercises.
PMID- 26423980
TI - A Primer on Quantitative Modeling.
AB - Caenorhabditis elegans is particularly suitable for obtaining quantitative data
about behavior, neuronal activity, gene expression, ecological interactions,
quantitative traits, and much more. To exploit the full potential of these data
one seeks to interpret them within quantitative models. Using two examples from
the C. elegans literature we briefly explore several types of modeling approaches
relevant to worm biology, and show how they might be used to interpret data,
formulate testable hypotheses, and suggest new experiments. We emphasize that the
choice of modeling approach is strongly dependent on the questions of interest
and the type of available knowledge.
PMID- 26423981
TI - Comments on the review article 'Time trends in the incidence and prevalence of
multiple sclerosis in Norway during eight decades'.
PMID- 26423982
TI - Physical examination tests for screening and diagnosis of cervicogenic headache:
A systematic review.
AB - It has been suggested that differential diagnosis of headaches should consist of
a robust subjective examination and a detailed physical examination of the
cervical spine. Cervicogenic headache (CGH) is a form of headache that involves
referred pain from the neck. To our knowledge, no studies have summarized the
reliability and diagnostic accuracy of physical examination tests for CGH. The
aim of this study was to summarize the reliability and diagnostic accuracy of
physical examination tests used to diagnose CGH. A systematic review following
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
guidelines was performed in four electronic databases (MEDLINE, Web of Science,
Embase and Scopus). Full text reports concerning physical tests for the diagnosis
of CGH which reported the clinometric properties for assessment of CGH, were
included and screened for methodological quality. Quality Appraisal for
Reliability Studies (QAREL) and Quality Assessment of Studies of Diagnostic
Accuracy (QUADAS-2) scores were completed to assess article quality. Eight
articles were retrieved for quality assessment and data extraction. Studies
investigating diagnostic reliability of physical examination tests for CGH scored
poorer on methodological quality (higher risk of bias) than those of diagnostic
accuracy. There is sufficient evidence showing high levels of reliability and
diagnostic accuracy of the selected physical examination tests for the diagnosis
of CGH. The cervical flexion-rotation test (CFRT) exhibited both the highest
reliability and the strongest diagnostic accuracy for the diagnosis of CGH.
PMID- 26423983
TI - The effects of a self-observation-based meditation intervention on acceptance or
rejection of the other.
AB - Research has demonstrated the many benefits of mindfulness training programmes
for individual health and well-being. This study, however, explored whether
mindfulness training might have effects on intergroup interaction. We tested the
effects of a self-observation-based mindfulness course on several dimensions of
acceptance of the other (i.e., non-judgement, non-reaction and observation). An
initial study test a mindfulness course training (N = 197). A second study then
tested its effect on intergroup relationships (N = 120). A control group was used
in both studies, and the subjects were tested before and after the course.
Results indicate that participation in the course favoured intergroup acceptance
of the other and suggest that mindfulness training represents a useful
educational method for reducing social discrimination.
PMID- 26423984
TI - Time for the UK to get ready for PrEP.
PMID- 26423985
TI - Therapeutic CCR5 blockade illuminates IRIS pathogenesis.
PMID- 26423986
TI - Home HIV testing and counselling: answers raising questions.
PMID- 26423987
TI - Which strategy for ART in resource-limited settings?
PMID- 26423988
TI - Churning in and out of HIV care.
PMID- 26423989
TI - Effect of the CCR5 antagonist maraviroc on the occurrence of immune
reconstitution inflammatory syndrome in HIV (CADIRIS): a double-blind,
randomised, placebo-controlled trial.
AB - BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a common
complication of antiretroviral therapy (ART) in patients with HIV. IRIS is
associated with an increased risk of admission to hospital and death. We assessed
whether CCR5 blockade with maraviroc reduces the risk of IRIS. METHODS: The
CADIRIS study was a double-blind, randomised, placebo-controlled trial that
recruited participants from five clinical sites in Mexico and one in South Africa
and followed them for 1 year. Patients were eligible if they were adults with
HIV, who were naive to ART, had CD4 count lower than 100 cells per MUL and HIV
RNA greater than 1000 copies per mL. Participants were randomly assigned (1:1) by
permuted block randomisation to receive either maraviroc (600 mg twice daily) or
placebo in addition to an ART regimen that included tenofovir, emtricitabine, and
efavirenz for 48 weeks. Patients, care providers, and members of the research
team were masked to treatment allocation. Clinical and laboratory evaluations
were done at baseline, and weeks 2, 4, 8, 12, 16, 24, 48, and 60. The primary
outcome was time to an IRIS event by 24 weeks. All patients who were randomly
assigned contributed to the primary time-to-event analysis from the date of ART
initiation until week 24, the time of an IRIS event or death. This trial is
registered with ClinicalTrials.gov, number NCT00988780. FINDINGS: Between Dec 10,
2009, and Jan 17, 2012, we screened 362 patients; of whom 279 met the inclusion
criteria and three refused to participate; thus 276 participants were randomly
assigned (140 to receive maraviroc and 136 to receive placebo). 64 (23%) patients
had IRIS events, 33 (24%) in the maraviroc group and 31 (23%) in the placebo
group (p=0.74). No difference in the time to IRIS events was noted between the
treatment groups (HR 1.08, 95% CI 0.66-1.77; log-rank test p=0.74). 37
participants (26%) in the maraviroc group had grade 3 or 4 adverse events
compared with 24 (18%) in placebo group; p=0.072); 25 (18%) in the maraviroc
group and 21 (15%) in the placebo group had serious treatment emergent adverse
events (p=0.63). INTERPRETATION: Maraviroc had no significant effect on
development of IRIS after ART initiation. Inclusion of this CCR5 inhibitor in an
initial treatment regimen does not confer a meaningful protection from the
occurrence of IRIS in people with advanced HIV infection. FUNDING: Pfizer.
PMID- 26423990
TI - Effectiveness and cost-effectiveness of potential responses to future high levels
of transmitted HIV drug resistance in antiretroviral drug-naive populations
beginning treatment: modelling study and economic analysis.
AB - BACKGROUND: With continued roll-out of antiretroviral therapy (ART) in resource
limited settings, evidence is emerging of increasing levels of transmitted drug
resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of
different potential public health responses to substantial levels of transmitted
drug resistance. METHODS: We created a model of HIV transmission, progression,
and the effects of ART, which accounted for resistance generation, transmission,
and disappearance of resistance from majority virus in the absence of drug
pressure. We simulated 5000 ART programmatic scenarios with different prevalence
levels of detectable resistance in people starting ART in 2017 (t0) who had not
previously been exposed to antiretroviral drugs. We used the model to predict
cost-effectiveness of various potential changes in policy triggered by different
prevalence levels of resistance to non-nucleoside reverse transcriptase
inhibitors (NNRTIs) measured in the population starting ART. FINDINGS: Individual
level resistance testing before ART initiation was not generally a cost-effective
option, irrespective of the cost-effectiveness threshold. At a cost-effectiveness
threshold of US$500 per quality-adjusted life-year (QALY), no change in policy
was cost effective (ie, no change in policy would involve paying less than $500
per QALY gained), irrespective of the prevalence of pretreatment NNRTI
resistance, because of the increased cost of the policy alternatives. At
thresholds of $1000 or higher, and with the prevalence of pretreatment NNRTI
resistance greater than 10%, a policy to measure viral load 6 months after ART
initiation became cost effective. The policy option to change the standard first
line treatment to a boosted protease inhibitor regimen became cost effective at a
prevalence of NNRTI resistance higher than 15%, for cost-effectiveness thresholds
greater than $2000. INTERPRETATION: Cost-effectiveness of potential policies to
adopt in response to different levels of pretreatment HIV drug resistance depends
on competing budgetary claims, reflected in the cost-effectiveness threshold.
Results from our model will help inform WHO recommendations on monitoring of HIV
drug resistance in people starting ART. FUNDING: WHO (with funds provided by the
Bill & Melinda Gates Foundation), CHAIN (European Commission).
PMID- 26423991
TI - Capsule Commentary on Richman et al., Colorectal Cancer Screening in the Era of
the Affordable Care Act.
PMID- 26423992
TI - A Systematic Review of Conceptual Frameworks of Medical Complexity and New Model
Development.
AB - BACKGROUND: Patient complexity is often operationalized by counting multiple
chronic conditions (MCC) without considering contextual factors that can affect
patient risk for adverse outcomes. OBJECTIVE: Our objective was to develop a
conceptual model of complexity addressing gaps identified in a review of
published conceptual models. DATA SOURCES: We searched for English-language
MEDLINE papers published between 1 January 2004 and 16 January 2014. Two
reviewers independently evaluated abstracts and all authors contributed to the
development of the conceptual model in an iterative process. RESULTS: From 1606
identified abstracts, six conceptual models were selected. One additional model
was identified through reference review. Each model had strengths, but several
constructs were not fully considered: 1) contextual factors; 2) dynamics of
complexity; 3) patients' preferences; 4) acute health shocks; and 5) resilience.
Our Cycle of Complexity model illustrates relationships between acute shocks and
medical events, healthcare access and utilization, workload and capacity, and
patient preferences in the context of interpersonal, organizational, and
community factors. CONCLUSIONS/IMPLICATIONS: This model may inform studies on the
etiology of and changes in complexity, the relationship between complexity and
patient outcomes, and intervention development to improve modifiable elements of
complex patients.
PMID- 26423995
TI - CCL22 Prevents Rejection of Mouse Islet Allografts and Induces Donor-Specific
Tolerance.
AB - Manipulation of regulatory T cell (Treg) migration by islet expression of the
chemokine CCL22 prevents diabetes in NOD mice and delays recurrent autoimmunity
in syngeneic islet transplants. We sought to determine whether attracting Tregs
with CCL22 also prevents islet allograft rejection. Isolated Bl/6 mouse islets
were transduced overnight with adenovirus expressing CCL22 (Ad-CCL22) downstream
of the CMV promoter. Islets were transplanted under the renal capsule of Balb/c
recipients made diabetic by streptozotocin. To assess immunologic tolerance,
graft-bearing kidneys from recipients of CCL22-expressing islet grafts were
removed, and mice received a second transplant of naive islets from the same
donor strain or third-party islets into the contralateral kidney. Adenoviral
expression of CCL22 conferred prolonged protection of islet allografts in MHC
mismatched, diabetic recipients, maintaining normoglycemia in 75% of recipients
for at least 80 days. Increased frequency of Treg cells was observed in islet
grafts transduced with Ad-CCL22 compared with untreated grafts. Normoglycemic
recipients of CCL22-expressing islet grafts showed complete absence of antidonor
antibodies and no lymphocyte proliferation after exposure to donor splenocytes.
After removal of the primary graft at day 80, mice that received a second
transplant with untreated islets from the same donor strain did not reject the
grafts, suggesting the development of tolerance. Expression of CCL22 recruits
Treg cells to transplanted islets, prevents activation of alloreactive T-cells
and islet allograft failure and induces alloantigen-specific tolerance.
Manipulation of Treg cells by CCL22 in transplanted islets may be a novel
therapeutic strategy for diabetes.
PMID- 26423993
TI - The continuing evolution of targeted therapy for inflammatory skin disease.
AB - Treatment of inflammatory skin disease has evolved from non-specific suppression
of immune cells to increasingly precise targeting and modulation of immune
mechanisms at all levels. This has led to dramatic treatment successes and
deepened understanding of the pathophysiology. The cycle of in vitro studies,
animal models, clinical trials, and case series of non-primary indications is a
feedback loop that informs and guides the design of ever better disease models
and therapeutic targets. Not only are we constantly discovering new molecules
driving skin inflammation, we have also found that psoriasis and other autoimmune
conditions are driven by distinct mediators occurring in early and late phases,
which could be an opportunity for phase-specific or multipronged interventions.
The deeper our mechanistic understanding, the more likely we will be able to
discover subtle strategies to reprogram each patients' immune cells without
having to dampen or eliminate their protective effects against pathogens and
tumors. Lastly, ongoing genomic studies might soon confirm interesting genetic
markers for predictive personalized medicine, the earliest currently being
evaluated in psoriasis such as HLA-Cw6 and TNFAIP3. Taken together, the continued
evolution of immune therapies in skin will potentially allow an unprecedented
form of medicine that is not bent on silencing the pathogenic mechanism, but
rather aims at using subtle interventions to shepherd the immune cell swarm back
on the correct path.
PMID- 26423996
TI - Small bowel varices secondary to chronic superior mesenteric vein thrombosis in a
patient with heterozygous Factor V Leiden mutation: a case report.
AB - INTRODUCTION: Bleeding ectopic small bowel varices pose a clinical dilemma for
the physician, given their diagnostic obscurity and the lack of evidence-based
medicine to guide therapy. They often occur in the context of portal
hypertension, secondary to either liver disease or extrahepatic causes. Rarely is
their presence associated with chronic superior mesenteric vein thrombosis and
hereditary coagulopathies. CASE PRESENTATION: A 74-year-old white woman, with a
heterozygous Factor V Leiden mutation and no underlying liver disease or portal
hypertension, presented over the course of 13 months for recurrent episodes of
melena and per rectal bleeding. An initial endoscopy showed a clean-based chronic
gastric ulcer, while colonoscopies showed multiple, non-bleeding angioectasias
which were treated with argon plasma coagulation. Subsequent video capsule
endoscopy and double balloon enteroscopy revealed red wale marks overlying
engorged submucosal veins in her distal ileum, consistent with ectopic varices. A
chronic superior mesenteric vein thrombus, found via computed tomography
venogram, was the cause of the ileal varices. She underwent curative surgical
resection of the affected bowel, with no re-bleeding episodes 17 months post
surgery, despite needing lifelong anticoagulation for recurrent venous
thromboembolisms. CONCLUSIONS: Clinicians should consider ectopic varices in
patients who present with obscure gastrointestinal bleeding, even in the absence
of portal hypertension or liver disease. In those with a known thrombophilia,
patients should be screened for splanchnic thrombosis, which may precipitate
ectopic varices.
PMID- 26423994
TI - HIV-1 tuberculosis-associated immune reconstitution inflammatory syndrome.
AB - Patients co-infected with HIV-1 and tuberculosis (TB) are at risk of developing
TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) following
commencement of antiretroviral therapy (ART). TB-IRIS is characterized by
transient but severe localized or systemic inflammatory reactions against
Mycobacterium tuberculosis antigens. Here, we review the risk factors and
clinical management of TB-IRIS, as well as the roles played by different aspects
of the immune response in contributing to TB-IRIS pathogenesis.
PMID- 26423997
TI - Factors associated with postpartum hemorrhage maternal death in referral
hospitals in Senegal and Mali: a cross-sectional epidemiological survey.
AB - BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal
mortality in Sub-Saharan-Africa (SSA). Although clinical guidelines treating PPH
are available, their implementation remains a great challenge in resource poor
settings. A better understanding of the factors associated with PPH maternal
mortality is critical for preventing risk of hospital-based maternal death. The
purpose of this study was thus to assess which factors contribute to maternal
death occurring during PPH. The factors were as follows: women's characteristics,
aspects of pregnancy and delivery; components of PPH management; and
organizational characteristics of the referral hospitals in Senegal and Mali.
METHODS: A cross-sectional survey nested in a cluster randomized trial (QUARITE
trial) was carried out in 46 referral hospitals during the pre-intervention
period from October 2007 to September 2008 in Senegal and Mali. Individual and
hospital characteristics data were collected through standardized questionnaires.
A multivariable logistic mixed model was used to identify the factors that were
significantly associated with PPH maternal death. RESULTS: Among the 3,278 women
who experienced PPH, 178 (5.4%) of them died before hospital discharge. The
factors that were significantly associated with PPH maternal mortality were: age
over 35 years (adjusted OR = 2.16 [1.26-3.72]), living in Mali (adjusted OR =
1.84 [1.13-3.00]), residing outside the region location of the hospital (adjusted
OR = 2.43 [1.29-4.56]), pre-existing chronic disease before pregnancy (adjusted
OR = 7.54 [2.54-22.44]), prepartum severe anemia (adjusted OR = 6.65 [3.77
11.74]), forceps or vacuum delivery (adjusted OR = 2.63 [1.19-5.81]), birth
weight greater than 4000 grs (adjusted OR = 2.54 [1.26-5.10]), transfusion
(adjusted OR = 2.17 [1.53-3.09]), transfer to another hospital (adjusted OR =
13.35 [6.20-28.76]). There was a smaller risk of PPH maternal death in hospitals
with gynecologist-obstetrician (adjusted OR = 0.55 [0.35-0.89]) than those with
only a general practitioner trained in emergency obstetric care (EmOC).
CONCLUSIONS: Our findings may have direct implications for preventing PPH
maternal death in resource poor settings. In particular, we suggest anemia should
be diagnosed and treated before delivery and inter-hospital transfer of women
should be improved, as well as the management of blood banks for a quicker access
to transfusion. Finally, an extent training of general practitioners in EmOC
would contribute to the decrease of PPH maternal mortality.
PMID- 26423998
TI - Identification and characterization of TIFY family genes in Brachypodium
distachyon.
AB - The TIFY family is a plant-specific gene family encoding proteins characterized
by a conserved TIFY domain. This family encodes four subfamilies of proteins,
including ZIM-like (ZML), TIFY, PPD and JASMONATE ZIM-Domain (JAZ) proteins. TIFY
proteins play important roles in plant development and stress responses. In this
study, 21 BdTIFYs were identified in Brachypodium distachyon through genome-wide
analysis, including 15 JAZ and 6 ZML genes. Analysis of the distribution of
conserved domains showed that there are three additional domains (CCT domain,
GATA domain and Jas domain) in the BdTIFY proteins besides the TIFY domain.
Phylogenetic analysis indicated that these 21 proteins were classified into two
major groups. Expression profile of BdTIFY genes in response to abiotic stresses
and phytohormones was analyzed using quantitative real-time RT-PCR. Among 21
BdTIFY genes, 12 of them were induced by JA treatment, and 4 of them were induced
by ABA treatment. Most of BdTIFY genes were responsive to one or more abiotic
stresses including drought, salinity, low temperature and heat. Especially,
BdTIFY5, 9a, 9b, 10c and 11a were significantly up-regulated by multiple abiotic
stresses. These results provided important clues for functional analysis of TIFY
family genes in B. distachyon.
PMID- 26423999
TI - Multiple and mass introductions from limited origins: genetic diversity and
structure of Solidago altissima in the native and invaded range.
AB - Understanding the origins and diversity of invasive species can reveal
introduction and invasion pathways, and inform an effective management of
invasive species. Tall goldenrod, Solidago altissima, is a herbaceous perennial
plant native to North America and it has become a widespread invasive weed in
East Asian countries. We used microsatellite and chloroplast DNA markers to
obtain information on neutral processes and on genetic diversity in native and
invaded populations of S. altissima and to infer how it invaded and spread in
Japan. We found that introduced (n = 12) and native (n = 20) populations had
similar levels of genetic diversity at nuclear SSR loci. Genetic structure
analysis indicated that at least two independent colonization events gave rise to
current S. altissima populations in Japan. The majority (68%) of the Japanese S.
altissima were genetically similar and likely shared a common origin from a
single or a small number of populations from the southern USA populations, while
the populations in Hokkaido were suggested to arise from a different source. Our
results suggest that multiple and mass introductions have contributed to the
persistence and rapid adaptation of S. altissima promoting its widespread
establishment throughout Japan.
PMID- 26424001
TI - Maternal exposure to GOS/inulin mixture prevents food allergies and promotes
tolerance in offspring in mice.
AB - BACKGROUND: Food allergies affect 4-8% of children and are constantly on the
rise, thus making allergies a timely issue. Most importantly, prevention
strategies are nonexistent, and current therapeutic strategies have limited
efficacy and need to be improved. One alternative to prevent or reduce allergies,
particularly during infancy, could consist of modulating maternal immunity and
microbiota using nondigestible food ingredients, such as prebiotics. For this
purpose, we studied the preventive effects of prebiotics in Balb/c mothers during
pregnancy and breastfeeding on food allergy development in offspring mice.
METHODS: After weaning, the offspring from mothers that were exposed to
GOS/inulin mixture or fed a control diet were intraperitoneally sensitized to
wheat proteins to induce a systemic allergic response and orally exposed to the
same allergen. Immunological, physiological, and microbial parameters were
analyzed. RESULTS: GOS/inulin mixture diet modified the microbiota of mothers and
their offspring. Offspring from mothers that received GOS/inulin prebiotics were
protected against food allergies and displayed lower clinical scores,
specifically of IgE and histamine levels, compared to offspring from mothers fed
a control diet. Moreover, GOS/inulin supplementation for the mother resulted in
stronger intestinal permeability in the offspring. Enhancement of the regulatory
response to allergic inflammation and changes in the Th2/Th1 balance toward a
dampened Th2 response were observed in mice from GOS/inulin mixture-exposed
mothers. CONCLUSION: The treatment of pregnant and lactating mice with
nondigestible GOS/inulin prebiotics promotes a long-term protective effect
against food allergies in the offspring.
PMID- 26424002
TI - Beginnings-The Kidney and Nephrology in Ancient Mesopotamian Culture.
AB - A defining period in the history of civilization occurred in ancient Mesopotamia.
While some of Mesopotamian contributions to knowledge (writing, mathematics,
astronomy) have been recognized, those made to medicine are just beginning to be
studied and appreciated. The medicine of the time developed in a theocratic
society where local gods controlled all aspects of life and their healers were
learned scribes who established the priestly medicine of old. For their use of
prayers and incantations as a component of therapy Mesopotamian medicine has been
belittled and relegated to magic. In fact, the Mesopotamian healers established
the basic medical skills of observation, diagnosis, prognosis and treatment and,
over time, systematically produced an expanding corpus of medical knowledge that
had not existed theretofore. The kidney as an organ, the components of the
urogenital tract, some signs and symptoms of renal diseases, and the art of
urinalysis were first conceptualized, studied, and codified in Mesopotamia. In
doing so, the Mesopotamians set the foundations of rational medicine that would
follow after the introduction of the phonetic alphabet and the Socratic method of
questioning and debate to stimulate critical analysis.
PMID- 26424000
TI - The epidemiology of subclinical malaria infections in South-East Asia: findings
from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and
Vietnam.
AB - BACKGROUND: The importance of the submicroscopic reservoir of Plasmodium
infections for malaria elimination depends on its size, which is generally
considered small in low transmission settings. The precise estimation of this
reservoir requires more sensitive parasite detection methods. The prevalence of
asymptomatic, sub-microscopic malaria was assessed by a sensitive, high blood
volume quantitative real-time polymerase chain reaction method in three countries
of the Greater Mekong Sub-region. METHODS: Cross-sectional surveys were conducted
in three villages in western Cambodia, four villages along the Thailand-Myanmar
border and four villages in southwest Vietnam. Malaria parasitaemia was assessed
by Plasmodium falciparum/pan malaria rapid diagnostic tests (RDTs), microscopy
and a high volume ultra-sensitive real-time polymerase chain reaction (HVUSqPCR:
limit of detection 22 parasites/mL). All villagers older than 6 months were
invited to participate. RESULTS: A census before the surveys identified 7355
residents in the study villages. Parasite prevalence was 224/5008 (4 %) by RDT,
229/5111 (5 %) by microscopy, and 988/4975 (20 %) when assessed by HVUSqPCR. Of
these 164 (3 %) were infected with P. falciparum, 357 (7 %) with Plasmodium
vivax, 56 (1 %) with a mixed infection, and 411 (8 %) had parasite densities that
were too low for species identification. A history of fever, male sex, and age of
15 years or older were independently associated with parasitaemia in a
multivariate regression model stratified by site. CONCLUSION: Light microscopy
and RDTs identified only a quarter of all parasitaemic participants. The
asymptomatic Plasmodium reservoir is considerable, even in low transmission
settings. Novel strategies are needed to eliminate this previously under
recognized reservoir of malaria transmission.
PMID- 26424003
TI - Gastric Sarcina ventriculi: incidental or pathologic?
PMID- 26424004
TI - Photoprotection as a Trait for Rice Yield Improvement: Status and Prospects.
AB - Solar radiation is essential for photosynthesis and global crop productivity but
it is also variable in space and time, frequently being limiting or in excess of
plant requirements depending on season, environment and microclimate.
Photoprotective mechanisms at the chloroplast level help to avoid oxidative
stress and photoinhibition, which is a light-induced reduction in photosynthetic
quantum efficiency often caused by damage to photosystem II. There is convincing
evidence that photoinhibition has a large impact on biomass production in crops
and this may be especially high in rice, which is typically exposed to high
tropical light levels. Thus far there has been little attention to
photoinhibition as a target for improvement of crop yield. However, we now have
sufficient evidence to examine avenues for alleviation of this particular stress
and the physiological and genetic basis for improvement in rice and other crops.
Here we examine this evidence and identify new areas for attention. In particular
we discuss how photoprotective mechanisms must be optimised at both the molecular
and the canopy level in order to coordinate with efficient photosynthetic
regulation and realise an increased biomass and yield in rice.
PMID- 26424005
TI - High genetic abundance of Rpi-blb2/Mi-1.2/Cami gene family in Solanaceae.
AB - BACKGROUND: Three NBS-LRR genes, Rpi-blb2, Mi-1.2, and Cami, constitute a very
special plant resistance gene family. These genes confer resistance against 4
distantly related pathogen species in 3 different Solanaceae hosts. To
characterize this noted resistance, we conducted a series of studies on this gene
family. RESULTS: First, homologs of this gene family were identified in the
pepper, tomato and potato genomes. This revealed a large variation in copy number
within this gene family among species and a great divergence was found both
between and within species. To gain more information pertaining to gene
resistance within this family, 121 LRR regions were cloned in 16 different
wild/cultivated potato accessions. Again, frequent copy number variations and a
high level of divergence between homolog were observed common among accessions.
The divergence within species was so high that it reaches the level of divergence
between species. Also, frequent frameshift mutations and abundant gene conversion
events were identified in these LRR regions. CONCLUSIONS: Our findings suggest
that this family harbors an unusually high level of genetic abundance, making it
of particular interest. Together with other reported examples, our study also
provides evidence that multi-resistance is a common trait in R gene families like
this.
PMID- 26424006
TI - High blood pressure is linked to increased risk of diabetes.
PMID- 26424007
TI - Biorevitalizing effect of a novel facial serum containing apple stem cell
extract, pro-collagen lipopeptide, creatine, and urea on skin aging signs.
AB - BACKGROUND: Epithelial regeneration in skin is achieved by the constant turnover
and differentiation of keratinocytes. Epidermal and dermal stem cells
compartments are fundamental for the continuous renewal of the skin. Adult stem
cells are the unique source for skin tissue renewal. Plants have stem cells and
plant derived stem cell extracts are now used in topical products for their
potential anti-ageing and anti-wrinkle effects. A new dermocosmetic product
containing apple stem cell extract, urea, creatine and palmitoyl tripeptide-38
(Ureadin Fusion Serum Lift Antiarrugas, ISDIN S.A), has been recently developed
to target different aspects involved in skin aging. STUDY AIM: To assess in vitro
the effects of this new serum on the metabolic functions of human senescent
fibroblasts and in vivo the anti-aging effects by clinical and instrumental
evaluation. METHODS: We evaluated the effects of the serum on the mitochondrial
ROS (reactive oxygen species) production in human senescent cultured fibroblasts
measured at 0.1% and 1% using the Mitoread AntiOx mtROS method. In addition we
evaluated the anti-ageing in vivo effect of this new serum applied on the face
twice daily for 28 consecutive days and assessed by clinical and instrumental
evaluation in 32 women with sensitive skin bearing wrinkles on crow's feet.
RESULTS: The tested serum both at 0.1% and 1% induces a significant increase in
02 consumption, cellular ATP level and a reduction in extra-cellular lactate
concentration. The product reduces also significantly the mitochondrial ROS
production. The clinical study shows a relevant anti-wrinkle effect in 71% of the
treated women with visible effects in 68% of the subjects as soon as 7 days of
treatment. A significant increase in dermal density and skin elasticity was also
observed. CONCLUSION: The use of this novel anti-aging serum demonstrated a
significant improvement of aging skin signs with first visible results achieved
after one week of use. The product seemed to optimize the metabolic functions in
human senescent cultured fibroblast restoring a more efficient cell metabolism
therefore contributing to the anti-aging properties of the product.
PMID- 26424008
TI - The garden in our gut.
PMID- 26424009
TI - Osthole Upregulates BDNF to Enhance Adult Hippocampal Neurogenesis in APP/PS1
Transgenic Mice.
AB - Adult hippocampal neurogenesis occurs in the dentate gyrus (DG) of the mouse
hippocampus, and plays roles in learning and memory progresses. In amyloid
precursor protein (APP)/presenilin 1 (PS1) transgenic mice, a rodent model of
Alzheimer's disease (AD), severe impairment of neurogenesis in the dentate
subgranular zone (SGZ) of the DG has been reported. Osthole, an active
constituent of Cnidium monnieri (L.) CUSSON, has been reported to exert
neuroprotective effects and may promote neural stem cell proliferation. However,
whether osthole ameliorates spatial memory deficits and improves hippocampal
neurogenesis in APP/PS1 mice remains unknown. In this study we found that osthole
(30 mg/kg intraperitoneally (i.p.) once daily) treatment dramatically ameliorated
the cognitive impairments by Morris Water Maze test and passive avoidance test,
and augmented neurogenesis in the DG of hippocampus in APP/PS1 mice. Furthermore,
osthole treatment upregulated expression of brain-derived neurotrophic factor
(BDNF) and enhanced activation of the BDNF receptor tyrosine receptor kinase B
(TrkB) following increased phosphorylation of cyclic AMP response element-binding
protein (CREB), indicating that osthole improves neurogenesis via stimulating
BDNF/TrkB/CREB signaling in APP/PS1 transgenic mice.
PMID- 26424010
TI - SPATA4 Counteracts Etoposide-Induced Apoptosis via Modulating Bcl-2 Family
Proteins in HeLa Cells.
AB - Spermatogenesis associated 4 (SPATA4) is a testis-specific gene first cloned by
our laboratory, and plays an important role in maintaining the physiological
function of germ cells. Accumulated evidence suggests that SPATA4 might be
associated with apoptosis. Here we established HeLa cells that stably expressed
SPATA4 to investigate the function of SPATA4 in apoptosis. SPATA4 protected HeLa
cells from etoposide-induced apoptosis through the mitochondrial apoptotic
pathway, in the way that SPATA4 suppressed decrease of the mitochondrial membrane
potential, the release of cytochrome c, and subsequent activation of caspase-9
and -3. We further demonstrated that SPATA4 upregulated anti-apoptotic members of
Bcl-2 family proteins, Bcl-2, and downregulated the pro-apoptotic member of Bcl-2
family proteins, Bax. Knockdown of SPATA4 in HeLa/SPATA4 cells could partially
rescue expression levels of bcl-2 and bax. In conclusion, SPATA4 protects HeLa
cells against etoposide-induced apoptosis through the mitochondrial apoptotic
pathway. Our findings provide further evidence that SPATA4 plays a role in
regulating apoptosis.
PMID- 26424011
TI - Relaxin Inhibits High Glucose-Induced Matrix Accumulation in Human Mesangial
Cells by Interfering with TGF-beta1 Production and Mesangial Cells Phenotypic
Transition.
AB - Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD).
DN is characterized by glomerular extracellular matrix accumulation, mesangial
expansion, basement membrane thickening, and renal interstitial fibrosis. To
date, mounting evidence has shown that H2 relaxin possesses powerful antifibrosis
properties; however, the mechanisms of H2 relaxin on diabetic nephropathy remain
unknown. Here, we aimed to explore whether H2 relaxin can reduce production of
extracellular matrix (ECM) secreted by human mesangial cells (HMC). HMC were
exposed to 5.5 mM glucose (NG) or 30 mM glucose (HG) with or without H2 relaxin.
Fibronectin (FN) and collagen type IV levels in the culture supernatants were
examined by solid-phase enzyme-linked immunoadsorbent assay (ELISA). Western blot
was used to detect the expression of alpha-smooth muscle actin (alpha-SMA)
protein. Quantitative polymerase chain reaction (qPCR) method was employed to
analyze transforming growth factor (TGF)-beta1 mRNA expression. Compared with the
normal glucose group, the levels of fibronectin and collagen type were markedly
increased after being cultured in high glucose medium. Compared with the high
glucose group, remarkable decreases of fibronectin, collagen type IV, alpha
smooth muscle actin, and TGF-beta1 mRNA expression were observed in the H2
relaxin-treated group. The mechanism by which H2 relaxin reduced high glucose
induced overproduction of ECM may be associated with inhibition of TGF-beta1 mRNA
expression and mesangial cells' phenotypic transition. H2 relaxin is a
potentially effective modality for the treatment of DN.
PMID- 26424012
TI - Mechanism of Action of Panaxytriol on Midazolam 1'-Hydroxylation and 4
Hydroxylation Mediated by CYP3A in Liver Microsomes and Rat Primary Hepatocytes.
AB - In our previous study, panaxytriol (PXT) was shown to enhance midazolam (MDZ) 1'
hydroxylation significantly but to inhibit MDZ 4-hydroxylation. To explore the
underlying mechanism, we investigated the effects of PXT on cytochrome P450 3A
(CYP3A)-mediated MDZ metabolic pathways using rat liver microsomes (RLM), human
liver microsomes (HLM), and rat primary hepatocytes. In the presence of PXT, the
Vmax of 4-OH MDZ decreased from 0.72 to 0.51 nmol/min.mg pro in RLM and from 0.32
to 0.12 nmol/min.mg pro in HLM, and the Km value increased from 5.12 to 7.26 uM
in RLM and from 27.87 to 32.80 uM in HLM. But the presence of PXT reduced the Km
and increased the Vmax values of MDZ 1'-hydroxylation in RLM and HLM.
Interestingly, the differential effect of PXT on MDZ 4-hydroxylation and 1'
hydroxylation was also observed in primary rat hepatocytes after 45-min culture.
PXT did not affect the expression levels of CYP3A1/2 mRNA in rat hepatocytes.
With extension of the culture time to 6 h, however, PXT significantly inhibited
both MDZ 4-hydroxylation and 1'-hydroxylation, and the expression level of
CYP3A1/2 mRNA was decreased to 87% and 80% (CYP3A1) and to 89% and 85% (CYP3A2)
of those in controls in the presence of PXT 4.0 and 8.0 ug/mL, respectively.
These results suggest that PXT could activate MDZ 1'-hydroxylation but inhibit
MDZ 4-hydroxylation by changing the CYP3A enzyme affinity and metabolic rate
after a short-term intervention. However, long-term treatment with PXT could
inhibit both the 4-hydroxylation and 1'-hydroxylation of MDZ by downregulating
CYP3A1/2 mRNA expression.
PMID- 26424013
TI - Electron Paramagnetic Resonance Study of the Free Radical Scavenging Capacity of
Curcumin and Its Demethoxy and Hydrogenated Derivatives.
AB - The quantitative free radical scavenging capacity of curcumin and its demethoxy
derivatives (demethoxycurcumin (Dmc) and bisdemethoxycurcumin (Bdmc)) and
hydrogenated derivatives (tetrahydrocurcumin (THC), hexahydrocurcumin (HHC) and
octahydrocurcumin (OHC)) towards 1,1-diphenyl-2-picryl hydrazyl (DPPH), nitric
oxide radical (NO), hydroxyl radical (HO(.)) and superoxide anion radical (O2(.))
were investigated by electron paramagnetic resonance (EPR) spectroscopy. One mole
of the hydrogenated derivatives scavenged about 4 mol of the DPPH radical, while
curcumin and Dmc scavenged about 3 mol of the DPPH radical. Curcumin and THC
showed moderate scavenging activity towards NO, yielding 200 mmol of NO scavenged
per 1 mol of the scavenger. In contrast, curcumin and its derivatives showed very
low scavenging activity towards HO(.) and O2(.), yielding approximately only 3-12
mmol scavenged per 1 mol of the tested compounds. Our results suggest that
curcumin and its derivatives principally act as chain breaking antioxidants
rather than as direct free radical scavengers. Furthermore, we showed that the
ortho-methoxyphenolic group and the heptadione linkage of these molecules greatly
contributed to their DPPH and NO scavenging activity.
PMID- 26424014
TI - Dioxin-Produced Alteration in the Profiles of Fecal and Urinary Metabolomes: A
Change in Bile Acids and Its Relevance to Toxicity.
AB - This study investigated dioxin-induced changes in metabolomes in pubertal rat
excrement. The administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or
restricting dietary intake (pair-fed group) markedly altered the metabolomic
profile including lipids, hormones, and vitamins in the urine and feces. TCDD
caused an increase in the fecal chenodeoxycholic acid and taurocholic acid
content and in urinary adrenaline and 17beta-estradiol, while the urinary
melatonin level was reduced by TCDD. These changes were not observed in the pair
fed group. In accordance with the elevated level of fecal bile acids, TCDD
reduced the intestinal expression of the apical sodium-dependent bile salt
transporter, which plays a role in resorbing bile acids from the bile duct. In
addition, CYP7A1, a rate-limiting enzyme for bile acid biosynthesis, was
attenuated by TCDD treatment, although TCDD induced hepatic CYP8B1, an enzyme
essential for cholic acid synthesis. Supplying cholic acid or chenodeoxycholic
acid to TCDD-exposed rats tended to restore the TCDD-produced reduction in serum
triglycerides, whereas no similar trend was observed in wasting syndrome and
lipid accumulation in the liver. These results suggest that: 1) TCDD alters the
circulating levels of bile acids and hormones via a mechanism distinct from an
attenuation in dietary intake, although the majority of TCDD-induced changes in
nutrient contents in the excrement is due to a reduction in food intake; and 2)
TCDD facilitates the excretion of bile acids and disrupts their biosynthesis,
resulting in the disturbance of lipid homeostasis.
PMID- 26424015
TI - Saturated Metabolism of Voriconazole N-Oxidation Resulting in Nonlinearity of
Pharmacokinetics of Voriconazole at Clinical Doses.
AB - Metabolic saturation of voriconazole based on the trough plasma concentrations of
voriconazole and its major metabolite N-oxide were evaluated according to CYP2C19
genotypes in 58 Japanese patients receiving voriconazole (median dose; 200 mg
twice daily) for prophylaxis or treatment. Predose trough plasma concentrations
of voriconazole and N-oxide were monitored on day 5 d or later after initiation
of voriconazole treatment. Large interindividual variations in trough plasma
concentrations of voriconazole and N-oxide were observed. Dose-normalized trough
plasma concentrations of voriconazole were strongly correlated with its absolute
trough concentrations, and the straight regression line between them intersected
close to the origin of the coordinates. No significant correlation was observed
between the trough plasma concentrations of voriconazole and N-oxide. The inverse
value of the metabolic ratio of N-oxide to voriconazole was strongly correlated
with the absolute trough voriconazole concentrations. No significant differences
in the trough plasma concentrations of voriconazole and N-oxide or the metabolic
ratio of N-oxide to voriconazole between the CYP2C19 genotypes were observed.
Saturated metabolism of voriconazole N-oxidation rather than CYP2C19 genotypes
contributed to the nonlinear pharmacokinetics. The metabolic process converting
voriconazole to N-oxide was saturated at the clinical dose.
PMID- 26424016
TI - Borrelidin Isolated from Streptomyces sp. Inhibited Adipocyte Differentiation in
3T3-L1 Cells via Several Factors Including GATA-Binding Protein 3.
AB - An inhibitor of 3T3-L1 adipocyte differentiation was isolated from Streptomyces
sp. TK08330 and identified by spectroscopy as the 18-membered macrolide
borrelidin. Treatment with 1.0 MUM borrelidin suppressed intracellular lipid
accumulation by 80% and inhibited the expression of adipocyte-specific genes.
Borrelidin suppressed the mRNA expression of two master regulators of adipocyte
differentiation, peroxisome proliferator-activated receptor gamma (PPARgamma) and
CCAAT/enhancer binding protein (C/EBPalpha). Studies on well-known upstream
regulators of PPARgamma revealed that borrelidin down-regulated C/EBPdelta mRNA
expression but did not affect expression of C/EBPbeta. Borrelidin increased mRNA
expression of negative regulators of differentiation such as GATA-binding protein
(GATA) 3, Kruppel-like factor (KLF) 3 and KLF7, as well as positive regulators,
KLF4, KLF6 and KLF15, at early stages of differentiation. To elucidate a primary
mediator of borrelidin differentiation inhibitory activity, small interfering RNA
(siRNA) transfection experiments were performed. The mRNA expression of
PPARgamma, which was down-regulated by borrelidin, was not changed by KLF3 and
KLF7 siRNA treatment. In contrast, expression of PPARgamma in GATA-3 siRNA
treated cells was not significantly different from that of control siRNA-treated
cells. Borrelidin significantly inhibited lipid accumulation in control siRNA
treated cells, and treatment with GATA-3 siRNA slightly reduced the inhibitory
effect of borrelidin. These results indicate that borrelidin inhibited adipocyte
differentiation partially via GATA-3.
PMID- 26424017
TI - PI3-Kinase Inhibitor LY294002 Repressed the Expression of Thrombin-Activatable
Fibrinolysis Inhibitor in Human Hepatoma HepG2 Cells.
AB - Thrombin-activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like
proenzyme biosynthesized in the liver and released into the blood circulation.
Activated TAFI (TAFIa) has been implicated as an important player in maintaining
the balance between blood coagulation and fibrinolysis. In the present study,
regulation of TAFI (CPB2) gene expression was investigated using cultured human
hepatoma HepG2 cells. HepG2 cells were treated with the phosphoinositide 3-kinase
(PI3K) inhibitor LY294002, and the levels of TAFI antigen and CPB2 mRNA were
measured. HepG2 cells treated with LY29400 decreased their release of TAFI
antigen into the conditioned medium (CM). In parallel, there were decreased
levels of CPB2 mRNA and TAFI antigen in the cells. However, CPB2 gene promoter
activity was not influenced by treatment of the cells with LY294002. The half
life of the CPB2 transcript was shortened by treatment with LY294002 compared
with control. The present results suggest that the PI3K inhibitor LY294002
suppresses expression of TAFI, a prothrombotic factor, by decreasing the
stability of CPB2 transcripts.
PMID- 26424018
TI - Vasodilator Effects of Elcatonin, a Synthetic Eel Calcitonin, on Retinal Blood
Vessels in Rats.
AB - The aim of this study was to examine the effects of elcatonin, a synthetic
derivative of eel calcitonin, on rat retinal blood vessels, and to determine how
diabetes affects the retinal vascular responses. Ocular fundus images were
captured with an original high-resolution digital fundus camera in vivo. The
retinal vascular responses were evaluated by measuring the diameter of retinal
blood vessels contained in the digital images. Both systemic blood pressure and
heart rate were continuously recorded. Elcatonin increased the diameter of
retinal blood vessels but decreased mean blood pressure in a dose-dependent
manner, whereas it had no significant effect on heart rate. A diminished retinal
vasodilator response and significant pressor response to elcatonin were observed
in rats injected intravenously with N(G)-nitro-L-arginine methyl ester, a nitric
oxide (NO) synthase inhibitor. Intravitreal injection of indomethacin, a non
selective cyclooxygenase (COX) inhibitor, and SQ22536, an adenylyl cyclase
inhibitor, markedly attenuated the vasodilator effects of elcatonin on retinal
blood vessels. The retinal vasodilator responses to elcatonin were unaffected 2
weeks after the induction of diabetes by a combination of streptozotocin
treatment and D-glucose feeding. These results suggest that elcatonin dilates rat
retinal blood vessels via NO- and COX-dependent mechanisms and that the adenylyl
cyclase-adenosine 3',5'-cyclic monophosphate system plays a major role in the
vasodilator mechanisms. The retinal vasodilatory effects of elcatonin seem to be
preserved at early stages of diabetes.
PMID- 26424019
TI - Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced
Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat.
AB - It is well known that rheumatoid arthritis patients taking nonsteroidal anti
inflammatory drugs (NSAIDs) are more susceptible to NSAIDs-induced
gastroenteropathy in comparison with other patients. In this study we demonstrate
that expression levels of interleukin (IL)-18 are related to aggravation of
intestinal ulcerogenic lesions in adjuvant-induced arthritis (AA) rats following
oral administration of indomethacin. AA rats were administered oral indomethacin
(40 mg/kg) and killed under deep isoflurane anesthesia after 24 h. The small
intestinal mucosa was then examined. Oral administration of indomethacin caused
hemorrhagic lesions in the small intestinal mucosa of AA rats, and the lesion
score of AA rats 24 h after indomethacin treatment was approximately 5.6-fold
higher than for normal rats administered indomethacin. IL-18 expression in the
small intestinal mucosa of AA rats administered indomethacin was also higher in
comparison with normal rats receiving indomethacin. In addition, interferon-gamma
and nitric oxide levels in the small intestinal mucosa of AA rats were increased
following oral administration of indomethacin. It is possible that IL-18
expression in AA rats renders the small intestinal mucosa more sensitive to
indomethacin, and that IL-18 may play a role in aggravating intestinal
ulcerogenic lesions in AA rats treated with this drug.
PMID- 26424020
TI - Obligatory Role of Early Ca(2+) Responses in H2O2-Induced beta-Cell Apoptosis.
AB - Our previous study using apoptosis analysis suggested that Ca(2+) release through
inositol 1,4,5-trisphosphate (IP3) receptors and the subsequent Ca(2+) influx
through store-operated channels (SOCs) constitute a triggering signal for H2O2
induced beta-cell apoptosis. In the present study, we further examined the
obligatory role of early Ca(2+) responses in beta-cell apoptosis induction. H2O2
induced elevation of the cytosolic Ca(2+) concentration ([Ca(2+)]c) consisting of
two phases: an initial transient [Ca(2+)]c elevation within 30 min and a slowly
developing one thereafter. The first phase was almost abolished by 2
aminoethoxydiphenylborate (2-APB), which blocks IP3 receptors and cation channels
including SOCs, while the second phase was only partially inhibited by 2-APB. The
inhibition by 2-APB of the second phase was not observed when 2-APB was added 30
min after the treatment with H2O2. 2-APB also largely inhibited elevation of the
mitochondrial Ca(2+) concentration ([Ca(2+)]m) induced by H2O2 when 2-APB was
applied simultaneously with H2O2, but not when applied 30 min after H2O2
application. In addition, 2-APB inhibited the release of mitochondrial cytochrome
c to the cytosol induced by H2O2 when 2-APB was applied simultaneously with H2O2
but not 30 min post-treatment. H2O2-induced [Ca(2+)]m elevation and cell death
were not inhibited by Ru360, an inhibitor of the mitochondrial calcium uniporter
(MCU). These results suggest that the H2O2-induced initial [Ca(2+)]c elevation,
occurring within 30 min and mediated by Ca(2+) release through IP3 receptors and
subsequent Ca(2+) influx through SOCs, leads to [Ca(2+)]m elevation, possibly
through a mechanism independent of MCU, thereby inducing cytochrome c release and
consequent apoptosis.
PMID- 26424021
TI - Biological Responsiveness and Metabolic Performance of Liposome-Encapsulated
Hemoglobin (Hemoglobin-Vesicles) in Apolipoprotein E-Deficient Mice after Massive
Intravenous Injection.
AB - The hemoglobin-vesicle (HbV), a vesicle in which a concentrated human hemoglobin
solution is encapsulated, was developed as an artificial oxygen carrier. Although
HbV has a favorable safety, metabolic, and excretion performance in healthy
animals, the effect of a massive amount of HbV, which also contains a large
amount of a lipid component including cholesterol, on physiological response and
metabolic performance under hyperlipidemic conditions is unclear. The aim of this
study was to evaluate whether administration of HbV causes toxicity in
apolipoprotein E-deficient mice (hyperlipidemic model mice). Apolipoprotein E
deficient mice were given a single injection of HbV (2000 mg hemoglobin/kg), and
physiological responses and metabolic profiles were monitored for 14 d
thereafter. All the mice tolerated the massive amount of HbV and survived, and
adequate biocompatibility was observed. Serum biochemical parameters indicate
that liver and kidney function were not remarkably affected, and morphological
changes in the liver and spleen were negligible. Lipid parameters in serum were
significantly increased until 3 d after HbV administration, but recovered within
7 d after the administration. In a pharmacokinetic study, HbV was mainly found
distributed in the liver and spleen, and disappeared from the body within 14 d.
In conclusion, even under conditions of hyperlipidemia, a massive dose of HbV and
its components resulted in favorable biological compatibility, metabolic, and
excretion profiles. These findings provide further support for the safety of HbV
for clinical use.
PMID- 26424022
TI - Preparation of a Monoclonal Antibody against Gintonin and Its Use in an Enzyme
Immunoassay.
AB - Gintonin is a novel ginseng-derived G protein-coupled lysophosphatidic acid (LPA)
receptor ligand. Gintonin elicits an [Ca(2+)]i transient in animal cells via
activation of LPA receptors. In vitro studies have shown that gintonin regulates
various calcium-dependent ion channels and receptors. In in vivo studies,
gintonin elicits anti-Alzheimer's disease activity through the activation of the
non-amyloidogenic pathway and anti-metastatic effects through the inhibition of
autotaxin. However, a method for gintonin quantitation in ginseng has not been
developed. In the present study, we developed an enzyme immunoassay (EIA) to
measure gintonin. A monoclonal antibody was raised in a mouse using gintonin as
the immunogen, and an indirect competitive EIA was used to measure gintonin. The
working range was 0.01-10 ug per assay. The anti-gintonin monoclonal antibody did
not cross-react with the ginsenosides Ra, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, and Rg3
or with LPAs such as LPA C16:0, LPA C18:0, LPA C18:1, and LPA C18:2. Using a
standard curve, we measured the amount of gintonin in various ginseng extract
fractions. Interestingly, we only detected a little amount of gintonin in
conventional hot water extracts of Korean red ginseng. However, we can measure
gintonin after ethanol extraction of Korean red ginseng marc. Thus, gintonin can
be extracted from ginseng with ethanol but not water, and the remaining Korean
red ginseng marc can be used to obtain gintonin. These results indicate that the
EIA with the anti-gintonin monoclonal antibody can be used to quantify gintonin
in various ginseng preparations, including commercial ginseng products.
PMID- 26424023
TI - Analysis of Neuropsychiatric Adverse Events in Patients Treated with Oseltamivir
in Spontaneous Adverse Event Reports.
AB - There have been concerns that oseltamivir causes neuropsychiatric adverse events
(NPAEs). We analyzed the association of age and gender with NPAEs in patients
treated with oseltamivir using a logistic regression model. NPAE data were
obtained from the U.S. Food and Drug Administration Adverse Event Reporting
System (2004 to 2013). The lower limit of the reporting odds ratio (ROR) 95%
confidence interval (CI) of "abnormal behavior" in Japan, Singapore, and Taiwan
was >=1. The effects of the interaction terms for oseltamivir in male patients
aged 10-19 years were statistically significant. The adjusted ROR of "abnormal
behavior" was 96.4 (95% CI, 77.5-119.9) in male patients aged 10-19 years treated
with osletamivir. In female patients, the results of the likelihood ratio test
for "abnormal behavior" were not statistically significant. The adjusted NPAE
RORs were increased in male and female patients under the age of 20 years.
Oseltamivir use could be associated with "abnormal behavior" in males aged 10-19
years. After considering the causality restraints of the current analysis,
further epidemiological studies are recommended.
PMID- 26424024
TI - Penetration of Ufenamate into Intact, Stripped, or Delipidized Skin Using
Different Vehicles.
AB - The purpose of this study was to clarify the effect of skin condition on skin
penetration of the very high lipophilic drug, ufenamate (UF). UF was applied to
stripped or delipidized skin using liquid paraffin (LP) or purified water
containing polysorbate 80 at a dose of 2 uL/cm(2). We found that UF penetration
into intact and stripped skin using a water vehicle was respectively 5 and 10
times higher than that using LP. UF is freely soluble in oil and insoluble in
water; thus, activity in water is higher than that in LP. Therefore, it is useful
to use a water-based vehicle for both intact sites and those with defective
stratum corneum (SC). Conversely, we found that delipidization of SC decreased
the penetration of UF significantly with both LP and water, and the amount
measured in the epidermis was 1 ug/cm(2) with both vehicles. This indicates that
UF is not suitable for so-called "dry skin." This study revealed clinically
relevant differences in the penetration of UF into intact, stripped, or
delipidized skin conditions.
PMID- 26424025
TI - Evaluation of Phosphatidylserine-Specific Peptide-Conjugated Liposomes Using a
Model System of Malaria-Infected Erythrocytes.
AB - Malaria is one of the most prevalent parasitic diseases and is most widespread in
tropical regions. The malarial parasite grows and reproduces in erythrocytes
during its life cycle, resulting in programmed erythrocyte death, termed
eryptosis. Lipid scrambling, which occurs following the exposure of anionic
lipids such as phosphatidylserine (PS) on the outer surface of erythrocytes, is a
characteristic physical change that occurs early during eryptosis. Here, we
prepared "PS specific peptide (PSP)"-conjugated liposomes (PSP-liposomes) and
investigated whether PSP-liposomes hold promise as a novel strategy for actively
targeting eryptosis. Eryptosis was induced by exposing red blood cells (RBCs) to
ionomycin, a known calcium ionophore. When PSP liposomes were mixed with either
RBCs or RBCs undergoing eryptosis (E-RBCs), the amount of PSP-liposome bound to E
RBCs was much higher than the amount bound to RBCs. However, the amount of PSP
liposome bound to E-RBCs was significantly inhibited by the presence of annexin V
protein, which binds specifically to PS. These results suggest that PSP-liposomes
could be an effective drug nanocarrier for treating E-RBCs and malaria-infected
erythrocytes.
PMID- 26424026
TI - Preparation of Antibodies and Development of an Enzyme-Linked Immunosorbent Assay
for the Tyrosine Kinase Inhibitors Lapatinib and Nilotinib.
AB - In this paper, we describe the production of the first specific antibodies
against the tyrosine kinase inhibitors lapatinib and nilotinib. Anti-lapatinib
antibody was obtained by immunizing rabbits with an antigen conjugated with
bovine serum albumin using 3-chloro-4-((3-fluorobenzyl)oxy)aniline. Anti
nilotinib antibody was produced by immunizing mice with an antigen conjugated
with bovine serum albumin using 2-(5-amino-2-methylanilino)-4-(3
pyridyl)pyrimidine. The generated antibodies were used to develop highly
sensitive and specific enzyme-linked immunosorbent assays (ELISAs) for lapatinib
and nilotinib in human serum. The assays were capable of detecting lapatinib and
nilotinib at serum concentrations as low as 40 and 8 ng/mL, respectively. Using
the two ELISAs, drugs levels were easily measured in the serum of rats after a
single dose oral administration of lapatinib or nilotinib. The assays are
therefore expected be valuable tools for therapeutic drug monitoring in the
clinical setting and pharmacokinetic studies of lapatinib and nilotinib.
PMID- 26424027
TI - Pomegranate Seed Oil Exerts Synergistic Effects with trans-Resveratrol in a Self
nanoemulsifying Drug Delivery System.
AB - Pomegranate seed oil (PSO) has diverse bioactivities. It was hyphothesized that
if PSO were employed to construct a trans-resveratrol-loaded self-nanoemulsifying
drug delivery system (RES SNEDDS-PSO), not only could PSO serve as an oil phase
but also exert synergistic effects with resveratrol to yield better therapeutic
outcomes. In this study, we prepared RES SNEDDS-PSO for the first time to
validate that hypothesis. The anti-inflammatory and anticancer activities of RES
SNEDDS-PSO were compared with another SNEDDS composed of oil phase isopropyl
palmitate (RES SNEDDS-IP). The results showed that upon exposure to a 10-fold
amount of water, RES SNEDDS-PSO was converted into nanoemulsions with a mean size
of 44 nm. Nanoemulsions enhanced the water solubility of resveratrol by 20-fold,
significantly improved resveratrol stability in intestinal fluid, and slowed the
decomposition of resveratrol in water by 1-fold. An in vivo anti-infection test
showed that the degree of inflammatory swelling in mice given RES SNEDDS-PSO was
only 60 and 76% that of the group fed with RES SNEDDS-IP at doses of 10 and 20
mg/kg, respectively. An in vitro anticancer study showed that the inhibitory rate
of RES SNEDDS-PSO against MCF-7 breast cancer cells was 2.03- and 1.24-fold that
of RES SNEDDS-IP at a concentration of 12.5 and 25 ug/mL, respectively. This
study demonstrated that the newly developed SNEDDS may be a prospective
formulation in the functional food and clinical fields.
PMID- 26424028
TI - Antimelanogenic Effects of Picrionoside A Isolated from the Leaves of Korean
Ginseng.
AB - This study was initiated to isolate active metabolites from the leaves of Panax
ginseng. Among them, picrionoside A, a megastigmane glucoside, was isolated from
the leaves of P. ginseng C. A. MAYER and its chemical structure was determined
based on spectroscopic methods, including FAB-MS, one-dimensional (1D)-NMR, 2D
NMR, and IR spectroscopy. Picrionoside A from P. ginseng has not been
investigated previously, and its biological or pharmaceutical activities have not
been reported elsewhere. The IC50 value of mushroom tyrosinase-inhibitory
activity of picrionoside A was 9.8 uM, and the rate of inhibition of synthesized
melanin content in melan-a cells was 17.1% at a concentration of 80 uM without
cytotoxicity. Furthermore, picrionoside A dramatically reduced body pigmentation
in the zebrafish model. Taken together, the results suggest that picrionoside A
isolated from the leaves of P. ginseng may be an effective skin-whitening agent
that could be a potent candidate material in the cosmetic industry.
PMID- 26424029
TI - Conformational Effects of the A21G Flemish Mutation on the Aggregation of Amyloid
beta Peptide.
AB - Among the various hereditary mutants of amyloid beta (Abeta) in familial
Alzheimer's disease (AD), the A21G Flemish-type mutant has unique properties
showing a low aggregation propensity but progressive deposition in vascular
walls. Moreover, in contrast to other familial AD cases that show extensive
Abeta1-42 deposition in the brain, patients with Flemish AD predominantly exhibit
the deposition of the Abeta1-40 isoform. Here we report the structural
characterization of the Flemish-type mutant (A21G) in comparison with the wild
type Abeta1-40 peptide to examine the possible effects of the A21G mutation on
the conformation of the Abeta1-40 isoform. The kinetic analysis of the
aggregation of the peptides monitored by thioflavin T fluorescence measurement
indicates that the mutation precludes the initial nucleation process of amyloid
fibril formation by Abeta1-40. Spectroscopic data indicate that the Flemish-type
mutant bound to aqueous micelles composed of lyso-GM1, in which the mobile N
terminal segment is tethered through the C-terminal helical segment, has reduced
alpha-helical structure compared to the wild-type peptide. Our findings suggest
that the mutational perturbation to the membrane binding properties is coupled
with the changes in nucleation behavior of Abeta during its fibril formation.
PMID- 26424030
TI - Simultaneous Determination Method of Epoxyeicosatrienoic Acids and
Dihydroxyeicosatrienoic Acids by LC-MS/MS System.
AB - Epoxyeicosatrienoic acids (EETs) are produced primarily by CYPs from arachidonic
acid (AA) and then further metabolized to the corresponding
dihydroxyeicosatrienoic acids (DHETs). EETs play important roles in physiological
processes such as regulating vasodilation and inflammation. Thus, the drug
inhibition of CYP-mediated AA metabolism could reduce production of EETs,
potentially resulting in adverse cardiovascular events. The aim of this study was
to develop a simple method to simultaneously determine the concentrations of both
EETs and DHETs using a conventional LC-MS/MS system to evaluate drug-endogenous
substance interactions, including eicosanoids. Eight eicosanoids (5,6-EET, 8,9
EET, 11,12-EET, 14,15-EET, 5,6-DHET, 8,9-DHET, 11,12-DHET, and 14,15-DHET) were
detected with their corresponding deuterium-labeled eicosanoids as internal
standards. The samples were purified by solid-phase extraction columns. Liquid
chromatographic separation was achieved on a C18 column. DHETs and EETs were
eluted at 4-7 and 18-26 min, respectively. The weighted (1/y(2)) calibration
curves were linear over a range of 5-2000 nmol/L for EETs and 2-2000 nmol/L for
DHETs. In quality control (QC) samples, the recoveries of eicosanoids were 95.2
118%. The intra-day precisions were within 6% in all three QC samples, and the
inter-day precisions were <16.7% at 50 nmol/L, <8.6% at 200 nmol/L, and <9.8% at
1000 nmol/L. We have applied this method for the determination of the eicosanoid
levels in samples from incubation studies of AA by using human recombinant CYP
enzyme (rCYP), and confirmed that the method has sensitivity sufficient for
assessment of rCYP incubation study.
PMID- 26424031
TI - Comments on torsional testing.
PMID- 26424032
TI - Quantitative Bioimaging to Investigate the Uptake of Mercury Species in
Drosophila melanogaster.
AB - The uptake of mercury species in the model organism Drosophila melanogaster was
investigated by elemental bioimaging using laser ablation-inductively coupled
plasma mass spectrometry (LA-ICPMS). The mercury distribution in Drosophila
melanogaster was analyzed for the three species mercury(II) chloride,
methylmercury chloride, and thimerosal after intoxication. A respective
analytical method was developed and applied to the analysis of the entire
Drosophila melanogaster first, before a particular focus was directed to the
cerebral areas of larvae and adult flies. For quantification of mercury, matrix
matched standards based on gelatin were prepared. Challenges of spatially
dissolved mercury determination, namely, strong evaporation issues of the
analytes and an inhomogeneous distribution of mercury in the standards due to
interactions with cysteine containing proteins of the gelatin were successfully
addressed by complexation with meso-2,3-dimercaptosuccinic acid (DMSA). No
mercury was detected in the cerebral region for mercury(II) chloride, whereas
both organic species showed the ability to cross the blood-brain barrier.
Quantitatively, the mercury level in the brain exceeded the fed concentration
indicating mercury enrichment, which was approximately 3 times higher for
methylmercury chloride than for thimerosal.
PMID- 26424033
TI - Correlates and predictors of loneliness in older-adults: a review of quantitative
results informed by qualitative insights.
AB - BACKGROUND: Older persons are particularly vulnerable to loneliness because of
common age-related changes and losses. This paper reviews predictors of
loneliness in the older population as described in the current literature and a
small qualitative study. METHODS: Peer-reviewed journal articles were identified
from psycINFO, MEDLINE, and Google Scholar from 2000-2012. Overall, 38 articles
were reviewed. Two focus groups were conducted asking older participants about
the causes of loneliness. RESULTS: Variables significantly associated with
loneliness in older adults were: female gender, non-married status, older age,
poor income, lower educational level, living alone, low quality of social
relationships, poor self-reported health, and poor functional status.
Psychological attributes associated with loneliness included poor mental health,
low self-efficacy beliefs, negative life events, and cognitive deficits. These
associations were mainly studied in cross-sectional studies. In the focus groups,
participants mentioned environmental barriers, unsafe neighborhoods, migration
patterns, inaccessible housing, and inadequate resources for socializing. Other
issues raised in the focus groups were the relationship between loneliness and
boredom and inactivity, the role of recent losses of family and friends, as well
as mental health issues, such as shame and fear. CONCLUSIONS: Future quantitative
studies are needed to examine the impact of physical and social environments on
loneliness in this population. It is important to better map the multiple factors
and ways by which they impact loneliness to develop better solutions for public
policy, city, and environmental planning, and individually based interventions.
This effort should be viewed as a public health priority.
PMID- 26424034
TI - Experimental and Calculated Spectra of pi-Stacked Mild Charge-Transfer Complexes:
Jet-Cooled Perylene.(Tetrachloroethene)n, n = 1,2.
AB - The S0 <-> S1 spectra of the mild charge-transfer (CT) complexes
perylene.tetrachloroethene (P.4ClE) and perylene.(tetrachloroethene)2 (P.(4ClE)2)
are investigated by two-color resonant two-photon ionization (2C-R2PI) and
dispersed fluorescence spectroscopy in supersonic jets. The S0 -> S1
vibrationless transitions of P.4ClE and P.(4ClE)2 are shifted by deltanu = -451
and -858 cm(-1) relative to perylene, translating to excited-state dissociation
energy increases of 5.4 and 10.3 kJ/mol, respectively. The red shift is ~30%
larger than that of perylene.trans-1,2-dichloroethene; therefore, the increase in
chlorination increases the excited-state stabilization and CT character of the
interaction, but the electronic excitation remains largely confined to the
perylene moiety. The 2C-R2PI and fluorescence spectra of P.4ClE exhibit strong
progressions in the perylene intramolecular twist (1au) vibration (42 cm(-1) in
S0 and 55 cm(-1) in S1), signaling that perylene deforms along its twist
coordinate upon electronic excitation. The intermolecular stretching (Tz) and
internal rotation (Rc) vibrations are weak; therefore, the P.4ClE intermolecular
potential energy surface (IPES) changes little during the S0 <-> S1 transition.
The minimum-energy structures and inter- and intramolecular vibrational
frequencies of P.4ClE and P.(4ClE)2 are calculated with the dispersion-corrected
density functional theory (DFT) methods B97-D3, omegaB97X-D, M06, and M06-2X and
the spin-consistent-scaled (SCS) variant of the approximate second-order coupled
cluster method, SCS-CC2. All methods predict the global minima to be pi-stacked
centered coplanar structures with the long axis of tetrachloroethene rotated by
tau ~ 60 degrees relative to the perylene long axis. The calculated binding
energies are in the range of -D0 = 28-35 kJ/mol. A second minimum is predicted
with tau ~ 25 degrees , with ~1 kJ/mol smaller binding energy. Although both
monomers are achiral, both the P.4ClE and P.(4ClE)2 complexes are chiral. The
best agreement for adiabatic excitation energies and vibrational frequencies is
observed for the omegaB97X-D and M06-2X DFT methods.
PMID- 26424035
TI - Expanding Indications of Gastric Electrical Stimulation.
PMID- 26424036
TI - Modulation of the Bitter Taste to Reduce Calorie Intake.
PMID- 26424037
TI - Is Interstitial Cells of Cajal-opathy Present in Gastroparesis?
AB - Gastroparesis (GP), defined as delayed gastric emptying in the absence of any
mechanical obstruction, is a challenging clinical condition, mainly because of
limited treatment options. Studies in animal models of delayed gastric emptying
as well as patients with gastroparesis revealed depletion or ultrastructural
changes of interstitial cells of Cajal (ICC) in the gastric tissue, recently
termed ICC-opathy. ICC are the pacemakers of the gastrointestinal tract and are
involved in the transmission of the neuronal signaling to the smooth muscles.
Therefore, lack of ICC could be one explanation of delayed gastric emptying in
gastroparetic patients. How frequently ICC changes are observed in gastroparesis
is not yet clear. In this review, the data on gastric ICC counts and morphology
in animal models and patients with gastroparesis are discussed.
PMID- 26424038
TI - Targeting Ion Channels: An Important Therapeutic Implication in Gastrointestinal
Dysmotility in Patients With Spinal Cord Injury.
AB - Gastrointestinal (GI) dysmotility is a severe, and common complication in
patients with spinal cord injury (SCI). Current therapeutic methods using
acetylcholine analogs or laxative agents have unwanted side effects, besides
often fail to have desired effect. Various ion channels such as ATP-sensitive
potassium (KATP) channel, calcium ions (Ca(2+))-activated potassium ions (K(+))
channels, voltage-sensitive Ca(2+) channels and chloride ion (Cl(-)) channels are
abundantly expressed in GI tissues, and play an important role in regulating GI
motility. The release of neurotransmitters from the enteric nerve terminal,
innervating GI interstitial cells of Cajal (ICC), and smooth muscle cells (SMC),
causes inactivation of K(+) and Cl(-) channels, increasing Ca(2+) influx into
cytoplasm, resulting in membrane depolarization and smooth muscle contraction.
Thus, agents directly regulating ion channels activity either in ICC or in SMC
may affect GI peristalsis and would be potential therapeutic target for the
treatment of GI dysmotility with SCI.
PMID- 26424039
TI - Association of the Extent of Atrophic Gastritis With Specific Dyspeptic Symptoms.
AB - BACKGROUND/AIMS: It remains unclear whether atrophic gastritis can affect
dyspeptic symptoms. We aimed to investigate whether the extent of atrophic
gastritis is associated with specific dyspeptic symptoms. METHODS: Consecutive
adults in a routine health-checkup program were enrolled in the study. The extent
of atrophic gastritis was classified into 3 groups based on the Kimura-Takemoto
criteria; the gastritis with no or little atrophy (group A: C0), the gastritis
with atrophy mainly in the antrum (group B: C1 and C2), and the gastritis with
atrophy in the large area of the corpus (group C: C3 and O). Upper
gastrointestinal symptoms were categorized into "typical reflux symptoms,"
"epigastric pain syndrome (EPS)-related symptoms," and "postprandial distress
syndrome (PDS)-related symptoms." RESULTS: A total of 1827 patients (1009 males,
mean age 45.1 years) were included in the analysis. The subgroups of atrophic
gastritis were as follows: group A (n = 1218, 66.7%), group B (n = 392, 21.4%),
and group C (n = 217, 11.9%). Typical reflux, EPS-related, and PDS-related
symptoms were present in 10.5%, 19.8%, and 16.2% of the subjects, respectively.
PDS-related and EPS-related symptoms were significantly more prevalent in the
group C of male patients and the group B of female patients, respectively,
compared with other groups. PDS-related and EPS-related symptoms were
independently associated with the group C in males (OR, 2.123; 95% CI, 1.090
4.136) and the group B in females (OR, 2.571; 95% CI, 1.319-5.025), respectively.
CONCLUSIONS: The extent of atrophic gastritis appears to affect the generation of
specific dyspeptic symptoms in a gender-dependent manner.
PMID- 26424040
TI - Surgical Intervention to Rescue Hirschsprung Disease in a Rat Model.
AB - BACKGROUND/AIMS: Rats with a spontaneous null mutation in endothelin receptor
type B or Ednrb (sl/sl; spotting lethal) lack enteric neurons in the distal bowel
and usually die within the first week after birth. This early postnatal lethality
limits their use for examining the potential of cell therapy to treat
Hirschsprung disease, and for studies of the influence of EDNRB on the mature CNS
and vascular systems. METHODS: We have developed a surgical intervention to
prolong the life of the spotting lethal sl/sl rat, in which we perform a
colostomy on postnatal (P) day 4-6 rats to avoid the fatal obstruction caused by
the lack of colonic enteric neurons. RESULTS: The stomas remained patent and
functional and the rats matured normally following surgery. Weight gains were
comparable between control and Hirschsprung phenotype (sl/sl) rats, which were
followed until 4 weeks after surgery (5 weeks old). We confirmed the absence of
enteric neurons in the distal colon of rats whose lives were saved by the
surgical intervention. CONCLUSIONS: This study provides a novel approach for
studying EDNRB signalling in multiple organ systems in mature rats, including an
animal model to study the efficacy of cell therapy to treat Hirschsprung disease.
PMID- 26424041
TI - Molecular and Cellular Characteristics of the Colonic Pseudo-obstruction in
Patients With Intractable Constipation.
AB - BACKGROUND/AIMS: Chronic intestinal pseudo-obstruction (CIPO) is a disorder
characterized by recurrent symptoms suggestive of obstruction such as abdominal
pain, proximal distension with extremely suppressed motility in the absence of
lumen-occluding lesion, whose etiology/ pathophysiology is poorly understood. In
this study we investigated a functionally obstructive lesion that could underlie
symptoms of CIPO. METHODS: We studied colons surgically removed from 13 patients
exhibiting clinical/pathological features of pseudo-obstruction but were
unresponsive to standard medical treatments. The colons were characterized
morphologically, functionally and molecularly, which were compared between
regions and to 28 region-matched controls obtained from colon cancer patients.
RESULTS: The colons with pseudo-obstruction exhibited persistent luminal
distension proximally, where the smooth muscle was hypertrophied with changes in
the cell phenotypes. Distinct luminal narrowing was observed near the distal end
of the dilated region, close to the splenic flexure, previously referred to as
the "transition zone (TZ)" between the dilated and non-dilated loops. Circular
muscles from the TZ responded less to depolarization and cholinergic stimulation,
which was associated with downregulation of L-type calcium channel expression.
Smooth muscle contractile protein was also downregulated. Myenteric ganglia and
neuronal nitric oxide synthase (nNOS) positive cells were deficient, more
severely in the TZ region. Interstitial cells of Cajal was relatively less
affected. CONCLUSIONS: The TZ may be the principal site of functional
obstruction, leading to proximal distension and smooth muscle hypertrophy, in
which partial nNOS depletion could play a key role. The neuromuscular
abnormalities probably synergistically contributed to the extremely suppressed
motility observed in the colonic pseudo-obstruction.
PMID- 26424042
TI - Corticotropin-releasing Factor Changes the Phenotype and Function of Dendritic
Cells in Mouse Mesenteric Lymph Nodes.
AB - BACKGROUND/AIMS: Dendritic cells (DCs) are a significant contributor to the
pathology of numerous chronic inflammatory autoimmune disorders; however, the
effects of Corticotropin-releasing factor (CRF) on intestinal DCs are poorly
understood. In this study, we investigated the role of CRF in alterations of
intestinal dendritic cell phenotype and function. METHODS: Mouse mesenteric lymph
node dendritic cells (MLNDCs) were obtained using magnetic bead sorting. Surface
expression of CRF receptor type 1 (CRF-R1) and CRF-R2 was determined by double
labeling immunofluorescence and quantitative polymerase chain reaction (qPCR) and
MLNDCs were subsequently exposed to CRF in the presence or absence of CRF-R1 and
CRF-R2 antagonists. Expression of surface molecules (MHC-I and MHC-II) and co
stimulatory molecules (CD80 and CD86) was determined by flow cytometric and
western blot analyses, and the T cell stimulatory capacity of MLNDCs was
evaluated by mixed lymphocyte reaction. RESULTS: Immunofluorescent staining and
quatitative polymerase chain reaction indicated that both the CRF receptors (CRF
R1 and CRF-2) are expressed on the surface of MLNDCs. Exposure to CRF increased
the expression of MHC-II on MLNDCs as well as their capacity to stimulate T cell
proliferation. MLNDCs treated with CRF-R1 antagonist exhibited a phenotype
characterized by a less activated state and reduced surface expression of MHC-II,
and consequently showed reduced capacity to stimulate T cells. In contrast,
treatment of MLNDCs with CRF-R2 antagonist yielded an opposite result.
CONCLUSIONS: CRF can alter the phenotype and function of intestinal DCs through
direct action on CRF-R1 and CRF-R2, and activation of the CRF-R1 and CRF-R2
pathways yields opposing outcomes.
PMID- 26424043
TI - Visceral Hypersensitivity and Altered Colonic Motility in Type 2 Diabetic Rat.
AB - BACKGROUND/AIMS: Abnormal visceral sensitivity and disordered motility are common
in patients with diabetes mellitus. The purpose of the present study was to
investigate whether visceral sensation and bowel motility were altered in a rat
model of type 2 diabetes mellitus accompanied by weight loss. METHODS: A type 2
diabetic rat model in adulthood was developed by administrating streptozotocin
(STZ; 90 mg/kg, i.p.) to neonatal rats. Eight weeks after STZ administration,
rats with blood glucose level of 200 mg/dL or higher were selected and used as
diabetic group (n = 35) in this study. Abdominal withdrawal reflex and arterial
pulse rate were measured to examine visceral nociception induced by colorectal
distension (0.1-1.0 mL). The amplitude, frequency, and area under the curve (AUC)
of spontaneous phasic contractions of colonic circular muscles were recorded in
vitro to examine colonic motility. RESULTS: STZ-treated diabetic rats gained
significantly less weight for 8 weeks than control (P < 0.01). Forty-eight
percent of the diabetic rats showed enhanced visceral nociceptive response to
colorectal distension. Diabetic rats did not differ from control rats in
colorectal compliance. However, the frequency and AUC, not the amplitude, of
colonic spontaneous contraction in vitro was significantly decreased in diabetic
rats compared to control rats (P < 0.01 in frequency and P < 0.05 in AUC).
CONCLUSIONS: These results demonstrate visceral hypersensitivity and colonic
dysmotility in a rat model of type 2 diabetes mellitus accompanied by weight
loss.
PMID- 26424046
TI - Clinical Significance of Esophageal Hypertensive Peristaltic Contractions on High
resolution Manometry(Neurogastroenterol Motil 2015;27:229-236).
PMID- 26424045
TI - Dysmotility Symptoms Are Independently Associated With Weight Change: A
Population-based Study of Australian Adults.
AB - BACKGROUND/AIMS: Weight loss is a recognized alarm symptom for organic
gastrointestinal (GI) disease, yet the association between weight change (loss or
gain) and specific GI symptoms remains poorly described. We assess the
associations between GI symptoms and weight change in a population-based sample
of Australian adults. METHODS: The prevalence of 26 GI symptoms was determined by
a postal survey to 5000 residents in western Sydney, Australia (60% response
rate). These were classified a priori into 5 symptom groups-abdominal pain,
esophageal symptoms, dysmotility symptoms, diarrhea and constipation. Weight
change was measured by two items which assessed weight loss and weight gain.
Clinically relevant weight change was defined as a loss or gain of 3 or more
kilograms in the past 3 months. RESULTS: Prevalence estimates for clinically
relevant weight loss and gain in the past 3 months were 10.3% and 8.1%,
respectively. When the 5 symptom groups were evaluated simultaneously, the
dysmotility symptoms of fullness after meals emerged as a predictor of both
weight loss (OR, 1.57; 95% CI, 1.32-1.88; P < 0.001) and weight gain (OR, 0.85;
95% CI, 0.72-0.99; P = 0.040), which also included bloating (OR, 1.64; 95% CI
1.46-1.84; P < 0.001). The associations remained significant following adjustment
for socio-economic status, body mass index, and eating behaviors. CONCLUSIONS:
Specific dysmotility symptoms are independently predictive of both weight loss
and weight gain. Different pathogenic mechanisms may be involved.
PMID- 26424044
TI - Serum Response Factor Is Essential for Prenatal Gastrointestinal Smooth Muscle
Development and Maintenance of Differentiated Phenotype.
AB - BACKGROUND/AIMS: Smooth muscle cells (SMCs) characteristically express serum
response factor (SRF), which regulates their development. The role of SRF in SMC
plasticity in the pathophysiological conditions of gastrointestinal (GI) tract is
less characterized. METHODS: We generated SMC-specific Srf knockout mice and
characterized the prenatally lethal phenotype using ultrasound biomicroscopy and
histological analysis. We used small bowel partial obstruction surgeries and
primary cell culture using cell-specific enhanced green fluorescent protein
(EGFP) mouse lines to study phenotypic and molecular changes of SMCs by
immunofluorescence, Western blotting, and quantitative polymerase chain reaction.
Finally we examined SRF change in human rectal prolapse tissue by
immunofluorescence. RESULTS: Congenital SMC-specific Srf knockout mice died
before birth and displayed severe GI and cardiac defects. Partial obstruction
resulted in an overall increase in SRF protein expression. However, individual
SMCs appeared to gradually lose SRF in the hypertrophic muscle. Cells expressing
low levels of SRF also expressed low levels of platelet-derived growth factor
receptor alpha (PDGFRalpha(low)) and Ki67. SMCs grown in culture recaptured the
phenotypic switch from differentiated SMCs to proliferative PDGFRalpha(low)
cells. The immediate and dramatic reduction of Srf and Myh11 mRNA expression
confirmed the phenotypic change. Human rectal prolapse tissue also demonstrated
significant loss of SRF expression. CONCLUSIONS: SRF expression in SMCs is
essential for prenatal development of the GI tract and heart. Following partial
obstruction, SMCs down-regulate SRF to transition into proliferative
PDGFRalpha(low) cells that may represent a phenotype responsible for their
plasticity. These findings demonstrate that SRF also plays a critical role in the
remodeling process following GI injury.
PMID- 26424047
TI - Opioid-induced Lower Esophageal Sphincter Dysfunction.
PMID- 26424048
TI - Measuring Gastrointestinal Electrical Activity With Extracellular Electrodes:
Author's Reply.
PMID- 26424049
TI - Polyamine-oligonucleotide conjugates: a promising direction for nucleic acid
tools and therapeutics.
AB - Chemical modification and/or the conjugation of small functional molecules to
oligonucleotides have significantly improved their biological and biophysical
properties, addressing issues such as poor cell penetration, stability to
nucleases and low affinity for their targets. Here, the authors review the
literature reporting on the biophysical, biochemical and biological properties of
one particular class of modification - polyamine-oligonucleotide conjugates.
Naturally derived and synthetic polyamines have been grafted onto a variety of
oligonucleotide formats, including antisense oligonucleotides and siRNAs. In many
cases this has had beneficial effects on their properties such as target
hybridization, nuclease resistance, cellular uptake and activity. Polyamine
oligonucleotide conjugation, therefore, represents a promising direction for the
further development of oligonucleotide-based therapeutics and tools.
PMID- 26424051
TI - Creation of identical multiple focal spots with prescribed axial distribution.
AB - We present a scheme for the construction of coaxially equidistant multiple focal
spots with identical intensity profiles for each individual focus and a
predetermined number and spacing. To achieve this, the radiation field from an
antenna is reversed and then gathered by high numerical aperture objective
lenses. Radiation patterns from three types of line sources, i.e., the electric
current, magnetic current and electromagnetic current distributions, with cosine
squared taper are respectively employed to generate predominately longitudinally
polarized bright spots, azimuthally polarized doughnuts, and focal spots with a
perfect spherically symmetric intensity distribution. The required illuminations
at the pupil plane of a 4Pi focusing configuration for the creation of these
identical multiple focal spots can be easily derived by solving the inverse
problem of the antenna radiation field. These unique focal field distributions
may find potential applications in laser direct writing and optical microscopy,
as well as multiple-particle trapping, alignment, and acceleration along the
optical axis.
PMID- 26424052
TI - An adverse event capture and management system for cancer studies.
AB - BACKGROUND: Comprehensive capture of Adverse Events (AEs) is crucial for
monitoring for side effects of a therapy while assessing efficacy. For cancer
studies, the National Cancer Institute has developed the Common Terminology
Criteria for Adverse Events (CTCAE) as a required standard for recording
attributes and grading AEs. The AE assessments should be part of the Electronic
Health Record (EHR) system; yet, due to patient-centric EHR design and
implementation, many EHR's don't provide straightforward functions to assess
ongoing AEs to indicate a resolution or a grade change for clinical trials.
METHODS: At UAMS, we have implemented a standards-based Adverse Event Reporting
System (AERS) that is integrated with the Epic EHR and other research systems to
track new and existing AEs, including automated lab result grading in a
regulatory compliant manner. Within a patient's chart, providers can launch AERS,
which opens the patient's ongoing AEs as default and allows providers to assess
(resolution/ongoing) existing AEs. In another tab, it allows providers to create
a new AE. Also, we have separated symptoms from diagnoses in the CTCAE to
minimize inaccurate designation of the clinical observations. Upon completion of
assessments, a physician would submit the AEs to the EHR via a Health Level 7
(HL7) message and then to other systems utilizing a Representational State
Transfer Web Service. CONCLUSIONS: AERS currently supports CTCAE version 3 and 4
with more than 65 cancer studies and 350 patients on those studies. This type of
standard integrated into the EHR aids in research and data sharing in a
compliant, efficient, and safe manner.
PMID- 26424050
TI - Genome-wide association study identifies multiple susceptibility loci for glioma.
AB - Previous genome-wide association studies (GWASs) have shown that common genetic
variation contributes to the heritable risk of glioma. To identify new glioma
susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147
cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project
data as reference. After genotyping an additional 1,490 cases and 1,723 controls
we identify new risk loci for glioblastoma (GBM) at 12q23.33 (rs3851634, near
POLR3B, P=3.02 * 10(-9)) and non-GBM at 10q25.2 (rs11196067, near VTI1A, P=4.32 *
10(-8)), 11q23.2 (rs648044, near ZBTB16, P=6.26 * 10(-11)), 12q21.2 (rs12230172,
P=7.53 * 10(-11)) and 15q24.2 (rs1801591, near ETFA, P=5.71 * 10(-9)). Our
findings provide further insights into the genetic basis of the different glioma
subtypes.
PMID- 26424053
TI - Recent advances in Helicobacter pylori eradication.
PMID- 26424056
TI - Providing a lifeline for rural doctors.
PMID- 26424057
TI - Pain, pregnancy or Pilates - there is plenty to peruse.
PMID- 26424054
TI - MiR-125a-5p Decreases the Sensitivity of Treg cells Toward IL-6-Mediated
Conversion by Inhibiting IL-6R and STAT3 Expression.
AB - The transcription factor FOXP3 is essential for the differentiation and function
of regulatory T cells (Treg). It is established that the transcription factor
GATA-3 is induced in Treg cells under inflammatory conditions. GATA-3 stabilizes
FOXP3 levels to avoid the differentiation of Treg cells into inflammatory-like T
cells. The IL-6 signal pathway influences the sensitivity of Treg cells towards
instability. The mechanism of GATA-3 in regulating FOXP3 and its relation to the
IL-6 pathway remains unclear. Here we report how miR-125a-5p plays an important
role in regulating the conversion of Treg cells by IL-6. miR-125a-5p expression
is low in Treg cells under steady state conditions and can be induced by GATA-3
to inhibit the expression of IL-6R and STAT3. This finding reveals a GATA3/miR
125a-5p/IL-6R and STAT3/FOXP3 regulatory pathway, which determines how Treg cells
respond to inflammatory IL-6-rich conditions.
PMID- 26424058
TI - Match of the decade: risk management of concussion versus high-speed collisions
in the football codes.
PMID- 26424059
TI - Co-creation: a new approach to optimising research impact?
PMID- 26424060
TI - Teledermatologists' management of emergency skin conditions.
PMID- 26424061
TI - Hypoadrenalism secondary to topical corticosteroid-containing skin-lightening
cream: danger of over-the-counter cosmetic agents.
PMID- 26424062
TI - Rural v metro: geographical differences in sports injury hospital admissions
across Victoria.
PMID- 26424063
TI - Recent advances in type 1 diabetes.
AB - Type 1 diabetes (T1D) is caused by an autoimmune attack on pancreatic beta cells
that leads to insulin deficiency. The incidence of T1D in Australia has doubled
over the past 20 years. T1D treatment focuses on physiological insulin
replacement, aiming for near-normal blood glucose levels. Hypoglycaemia is a
significant cause of morbidity and mortality in T1D. Optimal T1D management is
complex, and is enhanced by empowering individuals in all aspects of managing
diabetes. New technologies, including insulin pumps, continuous glucose monitors
and sensor-augmented pumps, can assist people achieve better glycaemic control
and reduce the risk of severe hypoglycaemia. Women with T1D can achieve
significantly better outcomes during pregnancy and for their infants by planning
for their pregnancy and by intensive glycaemic control. Several trials are
underway that seek to identify the determinants of autoimmunity and to develop
therapies that prevent T1D in at-risk individuals. Pancreatic and islet cell
transplants are proven therapies, but are only offered to individuals with
diabetes and renal failure (pancreas) or severe hypoglycaemia unawareness (islet
cell transplants). Although T1D is still associated with considerable premature
mortality, recent findings show that a significant improvement in life expectancy
has occurred.
PMID- 26424064
TI - Unconventional natural gas development and human health: thoughts from the United
States.
AB - If unconventional gas development (UGD) continues to expand in Australia, the
potential health and environmental impacts should be adequately addressed and
preventive public health measures should be implemented. The United States has
embraced UGD and has decades of experience that could be beneficial to Australia
as stakeholders debate the potential benefits and harms of the technique.
Additional research on the health impacts of UGD is necessary. Baseline and trend
morbidity and mortality data need to be collected to assess changes in population
health over time. To date, few health or epidemiological studies have been
conducted, so it remains difficult to assess actual health outcomes. In the
absence of scientific consensus, there are two possible risks: failing to develop
unconventional natural gas when the harms are manageable; or developing it when
the harms are substantial. Many government bodies around the world have chosen to
minimise the risk of the latter until the impacts of UGD are better understood.
Policies should be informed by empirical evidence based on actual experience
rather than assurance of best practices. There is a strong rationale for
precautionary measures based on the health and environmental risks identified in
the scientific literature.
PMID- 26424065
TI - The stability of rural outreach services: a national longitudinal study of
specialist doctors.
AB - OBJECTIVE: To explore the characteristics of specialists who provide ongoing
rural outreach services and whether the nature of their service patterns
contributes to ongoing outreach. DESIGN, PARTICIPANTS AND SETTING: Specialist
doctors providing rural outreach in a large longitudinal survey of Australian
doctors in 2008, together with new entrants to the survey in 2009, were followed
up to 2011. MAIN OUTCOME MEASURES: Providing outreach services to the same rural
town for at least 3 years. RESULTS: Of 953 specialists who initially provided
rural outreach services, follow-up data were available for 848. Overall, 440
specialists (51.9%) provided ongoing outreach services. Multivariate analysis
found that participation was associated with being male (odds ratio [OR], 1.82;
95% CI, 1.28-2.60), in mid-career (45-64 years old; OR, 1.44; 95% CI, 1.04-1.99),
and working in mixed, mainly private practice (OR, 1.73; 95% CI, 1.18-2.53).
Specialists working only privately were less likely to provide ongoing outreach
(OR 0.51; 95% CI, 0.32-0.82), whereas metropolitan and rural-based specialists
were equally likely to do so. Separate univariate analysis showed travelling
further to remote towns had no effect on ongoing service provision. Outreach to
smaller towns was associated with improved stability. CONCLUSIONS: Around half of
specialists providing rural outreach services continue to visit the same town on
an ongoing basis. More targeted outreach service strategies should account for
career stage and practice conditions to help sustain access. Financial incentives
may increase ongoing service provision by specialists only working privately.
There is some indication that outreach services delivered to smaller communities
are more stable.
PMID- 26424066
TI - Safety of opioid patch initiation in Australian residential aged care.
AB - OBJECTIVE: To explore opioid use by aged care facility residents before and after
initiation of transdermal opioid patches. DESIGN: A cross-sectional cohort study,
analysing pharmacy data on individual patient supply between 1 July 2008 and 30
September 2013. SETTING: Sixty residential aged care facilities in New South
Wales. PARTICIPANTS: Residents receiving an initial opioid patch during the study
period. MAIN OUTCOME MEASURE: The proportion of residents who were opioid-naive
in the 4 weeks prior to patch initiation was determined. In addition, the patch
strength at initiation and the daily dose of transdermal patches and of
additional opioids 1 month after initiation were determined. RESULTS: An opioid
patch was initiated in 596 of 5297 residents (11.3%: 2.6% fentanyl, 8.7%
buprenorphine) in the 60 residential aged care facilities. The mean age at
initiation was 87 years, and 74% of the recipients were women. The proportion of
recipients who were opioid-naive before patch initiation was 34% for fentanyl and
49% for buprenorphine. Most were initiated at the lowest available patch
strength, and the dose was up-titrated after initiation. Around 15% of fentanyl
users and 10% of buprenorphine users needed additional regular opioids after
patch initiation. CONCLUSIONS: The results suggest some inappropriate initiation
of opioid patches in Australian residential aged care facilities. Contrary to
best practice, a third of residents initiated on fentanyl patches were opioid
naive in the 4 weeks before initiation.
PMID- 26424067
TI - Trends and characteristics of accidental and intentional codeine overdose deaths
in Australia.
AB - OBJECTIVES: To examine trends in codeine-related mortality rates in Australia,
and the clinical and toxicological characteristics of codeine-related deaths.
DESIGN AND SETTING: Analysis of prospectively collected data from the National
Coronial Information System on deaths where codeine toxicity was determined to be
an underlying or contributory cause of death. The study period was 2000-2013.
MAIN OUTCOME MEASURES: Population-adjusted numbers (per million persons) of (1)
codeine-related deaths, classified by intent (accidental or intentional); and (2)
heroin- and Schedule 8 opioid-related deaths (as a comparator). RESULTS: The
overall rate of codeine-related deaths increased from 3.5 per million in 2000 to
8.7 per million in 2009. Deaths attributed to accidental overdoses were more
common (48.8%) than intentional deaths (34.7%), and their proportion increased
during the study period. High rates of prior comorbid mental health (53.6%),
substance use (36.1%) and chronic pain (35.8%) problems were recorded for these
deaths. For every two Schedule 8 opioid-related deaths in 2009, there was one
codeine-related death. Most codeine-related deaths (83.7%) were the result of
multiple drug toxicity. CONCLUSIONS: Codeine-related deaths (with and without
other drug toxicity) are increasing as the consumption of codeine-based products
increases. Educational messages are needed to better inform the public about the
potential harms of chronic codeine use, especially in the context of
polypharmacy.
PMID- 26424068
TI - Klebsiella pneumoniae liver abscess complicated by endogenous endophthalmitis:
the importance of early diagnosis and intervention.
PMID- 26424069
TI - Catecholamine-induced cardiomyopathy resulting from life-threatening funnel-web
spider envenoming.
PMID- 26424070
TI - Every year eventually becomes the year for the older person.
PMID- 26424072
TI - Quantification of regional leachate variance from municipal solid waste landfills
in China.
AB - The quantity of leachate is crucial when assessing pollution emanating from
municipal landfills. In most cases, existing leachate quantification measures
only take into account one source - precipitation, which resulted in serious
underestimation in China due to its waste properties: high moisture contents. To
overcome this problem, a new estimation method was established considering two
sources: (1) precipitation infiltrated throughout waste layers, which was
simulated with the HELP model, (2) water squeezed out of the waste itself, which
was theoretically calculated using actual data of Chinese waste. The two sources
depended on climate conditions and waste characteristics, respectively, which
both varied in different regions. In this study, 31 Chinese cities were
investigated and classified into three geographic regions according to landfill
leachate generation performance: northwestern China (China-NW) with semi-arid and
temperate climate and waste moisture content of about 46.0%, northern China
(China-N) with semi-humid and temperate climate and waste moisture content of
about 58.2%, and southern China (China-S) with humid and sub-tropical/tropical
climate and waste moisture content of about 58.2%. In China-NW, accumulated
leachate amounts were very low and mainly the result of waste degradation,
implying on-site spraying/irrigation or recirculation may be an economic approach
to treatment. In China-N, water squeezed out of waste by compaction totaled 22
45% of overall leachate amounts in the first 40 years, so decreasing the initial
moisture content of waste arriving at landfills could reduce leachate generation.
In China-S, the leachate generated by infiltrated precipitation after HDPE
geomembranes in top cover started failing, contributed more than 60% of the
overall amounts over 100 years of landfilling. Therefore, the quality and placing
of HDPE geomembranes in the top cover should be controlled strictly for the
purpose of mitigation leachate generation.
PMID- 26424073
TI - The diverse impact of advance care planning: a long-term follow-up study on
patients' and relatives' experiences.
AB - BACKGROUND: Advance care planning (ACP) is a process of discussing and recording
patients' preferences for future care, aiming to guide healthcare decisions at
the end of life (EOL). AIM: To explore nuances in the long-term impact of ACP by
studying patient and relative experiences. DESIGN: A qualitative follow-up
interview study. Interviews were recorded, transcribed and analysed using
thematic synthesis. SETTING/PARTICIPANTS: 3 patients with a life-limiting disease
(lung or heart disease), affiliated with a major Danish hospital, and 7 relatives
were interviewed 1 year after participating in an ACP discussion. RESULTS: The
experiences were diverse. Some patients and relatives felt 'relieved', 'more
secure' and more in control due to ACP. To some, ACP had led to open
communication rather than 'beating around the bush', and to spending more quality
time together. However, others perceived ACP as irrelevant. Some stated that the
patient's wishes had not been met regardless of ACP. Others felt that EOL
questions cannot be realistically considered until 'you're in the middle of it',
because many factors are involved. In one case, participating in ACP led to a
patient-relative conflict, resulting in EOL issues being 'tucked away'.
CONCLUSIONS: The study reveals great diversity in patient and relative
experiences of ACP. The study challenges previous research which mainly
emphasises ACP as a valuable tool to optimise EOL care. This study stresses the
importance of awareness of the highly individual nature of preferences and needs
of patients and relatives regarding information, involvement and communication
about EOL care.
PMID- 26424074
TI - Impact of Periconceptional Use of Nitrosatable Drugs on the Risk of Neural Tube
Defects.
AB - Nitrosatable drugs (NSDs) can, in the presence of nitrosating agents and highly
acidic conditions, form N-nitroso compounds that have been found to be
teratogenic in animal models. Using data from the Slone Epidemiology Center Birth
Defects Study collected from 1998 to 2012, we compared maternal periconceptional
NSD use between 334 neural tube defect cases and 7,619 nonmalformed controls. We
categorized NSDs according to their functional group (secondary amine, tertiary
amine, and amide). With logistic regression models, we estimated adjusted odds
ratios and 95% confidence intervals. Neural tube defect risk was associated with
maternal periconceptional use of secondary (adjusted odds ratio (aOR) = 1.7, 95%
confidence interval (CI): 1.1, 2.4) and tertiary (aOR = 1.7, 95% CI: 1.2, 2.5)
amines; an association was observed for amides, but the 95% confidence interval
included the null (aOR = 1.4, 95% CI: 0.7, 2.5). Within the secondary amine
group, elevated adjusted odds ratios were observed for 3 drugs but were null for
the remaining medications. Increases in risk were observed for both strata of
folic acid intake (<400 ug/day, >=400 ug/day), with a slightly higher risk in the
>=400-ug/day stratum. Our findings support previously reported positive
associations between neural tube defects and periconceptional exposure to NSDs
containing a secondary or tertiary amine or amide.
PMID- 26424076
TI - Assessing vibratory stimulation-induced cortical activity during a motor task--A
randomized clinical study.
AB - Effects of vibratory stimulation on motor performance have been widely
investigated. Many theories have been applied, in order to evaluate its influence
on individuals; however, very few studies have researched vibratory stimulation
induced cortical behavior. The aim of the present study is to investigate
behavioral changes, such as reaction time and index finger movements, as well as
electrophysiological changes, using beta band absolute power, in subjects
submitted to vibratory stimulation. For this study, 30 healthy subjects were
randomly selected and divided into two groups, experimental and control, and were
submitted to a right index finger task, before and after vibratory stimulation,
which was applied to the right upper limb, while their standard cerebral activity
was recorded through electroencephalogram. No significant difference was found
among behavioral variables. On the other hand, beta band absolute power
significantly increased in the experimental group for the C3, C4 and P4
derivations, while it decreased at P3. The results suggest that
electrophysiological changes were induced by vibratory stimulation, while
reaction time and task-related movements were not affected by it.
PMID- 26424075
TI - Elevated free fatty acid uptake via CD36 promotes epithelial-mesenchymal
transition in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related
death worldwide, and the factors influencing HCC progression are poorly
understood. Here we reveal that HCC progression via induction of epithelial
mesenchymal transition (EMT) is closely associated with the expression of
CD36/fatty acid translocase and elevated free fatty acid (FFA) levels. Although
obesity is manifested as elevated FFA levels, the degree of EMT was not
associated with the body mass index of the patients, highlighting the specific
roles of CD36 and FFA uptake. Treatment of human liver cancer cell lines with
FFAs exacerbated the EMT phenotype, whereas chemical inhibition of CD36 mitigated
these effects. Furthermore, the Wnt and TGF-beta signaling pathways were
activated upon FFA treatment, potentially acting as upstream activators of the
EMT program. These results provide the first direct evidence associating CD36 and
elevated FFAs with HCC progression.
PMID- 26424077
TI - Tetrodotoxin suppresses thermal hyperalgesia and mechanical allodynia in a rat
full thickness thermal injury pain model.
AB - Burn injuries have been identified as the primary cause of injury in 5% of U.S.
military personnel evacuated from Operations Iraqi Freedom and Enduring Freedom.
Severe burn-associated pain is typically treated with opioids such as fentanyl,
morphine, and methadone. Side effects of opioids include respiratory depression,
cardiac depression, decrease in motor and cognitive function, as well as the
development of hyperalgesia, tolerance and dependence. These effects have led us
to search for novel analgesics for the treatment of burn-associated pain in
wounded combat service members. Tetrodotoxin (TTX) is a selective voltage-gated
sodium channel blocker currently in clinical trials as an analgesic. A phase 3
clinical trial for cancer-related pain has been completed and phase 3 clinical
trials on chemotherapy-induced neuropathic pain are planned. It has also been
shown in mice to inhibit the development of chemotherapy-induced neuropathic
pain. TTX was originally identified as a neurotoxin in marine animals but has now
been shown to be safe in humans at therapeutic doses. The antinociceptive effects
of TTX are thought to be due to inhibition of Na(+) ion influx required for
initiation and conduction of nociceptive impulses. One TTX sensitive sodium
channel, Nav1.7, has been shown to be essential in lowering the heat pain
threshold after burn injuries. To date, the analgesic effect of TTX has not been
tested in burn-associated pain. Male Sprague-Dawley rats were subjected to a full
thickness thermal injury on the right hind paw. TTX (8 MUg/kg) was administered
once a day systemically by subcutaneous injection beginning 3 days post thermal
injury and continued through 7 days post thermal injury. Thermal hyperalgesia and
mechanical allodynia were assessed 60 and 120 min post injection on each day of
TTX treatment. TTX significantly reduced thermal hyperalgesia at all days tested
and had a less robust, but statistically significant suppressive effect on
mechanical allodynia. These results suggest that systemic TTX may be an
effective, rapidly acting analgesic for battlefield burn injuries and has the
potential for replacing or reducing the need for opioid analgesics.
PMID- 26424079
TI - The epidemiology of sepsis: questioning our understanding of the role of race.
AB - Race has been identified as an important risk factor for the development of
sepsis and as a predictor of poor outcomes in sepsis. For example, black
individuals have been demonstrated to be nearly twice as likely to develop sepsis
and to have greater mortality from sepsis than white individuals. Recent data
from a longitudinal cohort, which examined incident hospitalizations for
infections occurring among participants in the Reasons for Geographic and Racial
Differences in Stroke (REGARDS) cohort, contradicts this prior research.
Investigators determined that black participants were significantly less likely
than white participants to present to the hospital with either infection or
sepsis. Although these results are intriguing, they highlight our inadequate
understanding of the relationship between race and sepsis and motivate the need
for higher quality epidemiologic research to isolate the true role of race in the
development of sepsis.
PMID- 26424078
TI - The role of vancomycin in addition with colistin and meropenem against colistin
sensitive multidrug resistant Acinetobacter baumannii causing severe infections
in a Paediatric Intensive Care Unit.
AB - BACKGROUND: Acinetobacter baumannii has been associated with high morbidity and
mortality rates, even in pediatric patients. Therapeutic options are limited,
especially when the strain is multidrug resistant. METHODS: Clinical and
microbiological analyses of 4 cases of systemic infections caused by multi drug
resistant A. baumannii treated with colistin/vancomycin combination at a
Pediatric Intensive Care Unit were performed in order to explore the potential
synergistic activity of colistin plus vancomycin. All the patients were treated
with colistin, meropenem and vancomycin. RESULTS: Four severe infections due to
MDR A. baumannii were observed. All patients treated with colistin/vancomycin
combination had a positive outcome with no infection relapses. Most importantly,
no significant adverse events related to the simultaneous administration of COL
plus VAN were observed. In our in-vitro experiments, the synergistic effect of
the combination COL plus VAN showed an early bactericidal activity even at VAN
concentration of 16 mg/L, which reflects the serum trough concentrations obtained
in patients. DISCUSSION: An antimicrobial strategy based on the activity of
colistin plus vancomycin was in-vitro and in-vivo effective in life-threatening
infections caused by multidrug-resistant A. baumannii in a Pediatric Intensive
Care Unit, in the absence of adverse effects. Colistin plus vancomycin were
highly synergic and bactericidal against carbapenem-resistant, colistin sensitive
A. baumannii whereas the addition of meropenem did not enhance the in-vitro
activity of colistin plus vancomycin. CONCLUSIONS: Our results confirm existing
data on the potential synergistic activity of a therapeutic strategy including
colistin plus vancomycin and provide important new clinical information for its
potential use as a therapeutic option against MDR A. baumannii infections,
especially in the pediatric population.
PMID- 26424080
TI - JRC GMO-Amplicons: a collection of nucleic acid sequences related to genetically
modified organisms.
AB - The DNA target sequence is the key element in designing detection methods for
genetically modified organisms (GMOs). Unfortunately this information is
frequently lacking, especially for unauthorized GMOs. In addition, patent
sequences are generally poorly annotated, buried in complex and extensive
documentation and hard to link to the corresponding GM event. Here, we present
the JRC GMO-Amplicons, a database of amplicons collected by screening public
nucleotide sequence databanks by in silico determination of PCR amplification
with reference methods for GMO analysis. The European Union Reference Laboratory
for Genetically Modified Food and Feed (EU-RL GMFF) provides these methods in the
GMOMETHODS database to support enforcement of EU legislation and GM food/feed
control. The JRC GMO-Amplicons database is composed of more than 240 000
amplicons, which can be easily accessed and screened through a web interface. To
our knowledge, this is the first attempt at pooling and collecting publicly
available sequences related to GMOs in food and feed. The JRC GMO-Amplicons
supports control laboratories in the design and assessment of GMO methods,
providing inter-alia in silico prediction of primers specificity and GM targets
coverage. The new tool can assist the laboratories in the analysis of complex
issues, such as the detection and identification of unauthorized GMOs. Notably,
the JRC GMO-Amplicons database allows the retrieval and characterization of GMO
related sequences included in patents documentation. Finally, it can help
annotating poorly described GM sequences and identifying new relevant GMO-related
sequences in public databases. The JRC GMO-Amplicons is freely accessible through
a web-based portal that is hosted on the EU-RL GMFF website. Database URL:
http://gmo-crl.jrc.ec.europa.eu/jrcgmoamplicons/.
PMID- 26424081
TI - Sample data processing in an additive and reproducible taxonomic workflow by
using character data persistently linked to preserved individual specimens.
AB - We present the model and implementation of a workflow that blazes a trail in
systematic biology for the re-usability of character data (data on any kind of
characters of pheno- and genotypes of organisms) and their additivity from
specimen to taxon level. We take into account that any taxon characterization is
based on a limited set of sampled individuals and characters, and that
consequently any new individual and any new character may affect the recognition
of biological entities and/or the subsequent delimitation and characterization of
a taxon. Taxon concepts thus frequently change during the knowledge generation
process in systematic biology. Structured character data are therefore not only
needed for the knowledge generation process but also for easily adapting
characterizations of taxa. We aim to facilitate the construction and
reproducibility of taxon characterizations from structured character data of
changing sample sets by establishing a stable and unambiguous association between
each sampled individual and the data processed from it. Our workflow
implementation uses the European Distributed Institute of Taxonomy Platform, a
comprehensive taxonomic data management and publication environment to: (i)
establish a reproducible connection between sampled individuals and all samples
derived from them; (ii) stably link sample-based character data with the metadata
of the respective samples; (iii) record and store structured specimen-based
character data in formats allowing data exchange; (iv) reversibly assign sample
metadata and character datasets to taxa in an editable classification and display
them and (v) organize data exchange via standard exchange formats and enable the
link between the character datasets and samples in research collections, ensuring
high visibility and instant re-usability of the data. The workflow implemented
will contribute to organizing the interface between phylogenetic analysis and
revisionary taxonomic or monographic work. DATABASE URL: http://campanula.e
taxonomy.net/.
PMID- 26424082
TI - RegNetwork: an integrated database of transcriptional and post-transcriptional
regulatory networks in human and mouse.
AB - Transcriptional and post-transcriptional regulation of gene expression is of
fundamental importance to numerous biological processes. Nowadays, an increasing
amount of gene regulatory relationships have been documented in various databases
and literature. However, to more efficiently exploit such knowledge for
biomedical research and applications, it is necessary to construct a genome-wide
regulatory network database to integrate the information on gene regulatory
relationships that are widely scattered in many different places. Therefore, in
this work, we build a knowledge-based database, named 'RegNetwork', of gene
regulatory networks for human and mouse by collecting and integrating the
documented regulatory interactions among transcription factors (TFs), microRNAs
(miRNAs) and target genes from 25 selected databases. Moreover, we also inferred
and incorporated potential regulatory relationships based on transcription factor
binding site (TFBS) motifs into RegNetwork. As a result, RegNetwork contains a
comprehensive set of experimentally observed or predicted transcriptional and
post-transcriptional regulatory relationships, and the database framework is
flexibly designed for potential extensions to include gene regulatory networks
for other organisms in the future. Based on RegNetwork, we characterized the
statistical and topological properties of genome-wide regulatory networks for
human and mouse, we also extracted and interpreted simple yet important network
motifs that involve the interplays between TF-miRNA and their targets. In
summary, RegNetwork provides an integrated resource on the prior information for
gene regulatory relationships, and it enables us to further investigate context
specific transcriptional and post-transcriptional regulatory interactions based
on domain-specific experimental data. Database URL: http://www.regnetworkweb.org.
PMID- 26424083
TI - MGDB: a comprehensive database of genes involved in melanoma.
AB - The Melanoma Gene Database (MGDB) is a manually curated catalog of molecular
genetic data relating to genes involved in melanoma. The main purpose of this
database is to establish a network of melanoma related genes and to facilitate
the mechanistic study of melanoma tumorigenesis. The entries describing the
relationships between melanoma and genes in the current release were manually
extracted from PubMed abstracts, which contains cumulative to date 527 human
melanoma genes (422 protein-coding and 105 non-coding genes). Each melanoma gene
was annotated in seven different aspects (General Information, Expression,
Methylation, Mutation, Interaction, Pathway and Drug). In addition, manually
curated literature references have also been provided to support the inclusion of
the gene in MGDB and establish its association with melanoma. MGDB has a user
friendly web interface with multiple browse and search functions. We hoped MGDB
will enrich our knowledge about melanoma genetics and serve as a useful
complement to the existing public resources. Database URL:
http://bioinfo.ahu.edu.cn:8080/Melanoma/index.jsp.
PMID- 26424084
TI - miRSponge: a manually curated database for experimentally supported miRNA sponges
and ceRNAs.
AB - In this study, we describe miRSponge, a manually curated database, which aims at
providing an experimentally supported resource for microRNA (miRNA) sponges.
Recent evidence suggests that miRNAs are themselves regulated by competing
endogenous RNAs (ceRNAs) or 'miRNA sponges' that contain miRNA binding sites.
These competitive molecules can sequester miRNAs to prevent them interacting with
their natural targets to play critical roles in various biological and
pathological processes. It has become increasingly important to develop a high
quality database to record and store ceRNA data to support future studies. To
this end, we have established the experimentally supported miRSponge database
that contains data on 599 miRNA-sponge interactions and 463 ceRNA relationships
from 11 species following manual curating from nearly 1200 published articles.
Database classes include endogenously generated molecules including coding genes,
pseudogenes, long non-coding RNAs and circular RNAs, along with exogenously
introduced molecules including viral RNAs and artificial engineered sponges.
Approximately 70% of the interactions were identified experimentally in disease
states. miRSponge provides a user-friendly interface for convenient browsing,
retrieval and downloading of dataset. A submission page is also included to allow
researchers to submit newly validated miRNA sponge data. Database URL:
http://www.bio-bigdata.net/miRSponge.
PMID- 26424085
TI - Characteristics of young people with long term conditions close to transfer to
adult health services.
AB - BACKGROUND: For many young people with long term conditions (LTC), transferring
from paediatric to adult health services can be difficult and outcomes are often
reported to be poor. We report the characteristics and representativeness of
three groups of young people with LTCs as they approach transfer to adult
services: those with autism spectrum disorder with additional mental health
problems (ASD); cerebral palsy (CP); or diabetes. METHODS: Young people aged 14
years-18 years 11 months with ASD, or those with diabetes were identified from
children's services and those with CP from population databases. Questionnaires,
completed by the young person and a parent, included the 'Mind the Gap' Scale,
the Rotterdam Transition Profile, and the Warwick and Edinburgh Mental Wellbeing
Scale. RESULTS: Three hundred seventy four young people joined the study; 118
with ASD, 106 with CP, and 150 with diabetes. Participants had a significant (p <
0.001) but not substantial difference in socio-economic status (less deprived)
compared to those who declined to take part or did not respond. Condition
specific severity of participants was similar to that of population data.
Satisfaction with services was good as the 'gap' scores (the difference between
their ideal and current care) reported by parents and young people were small.
Parents' satisfaction was significantly lower than their children's (p < 0.001).
On every domain of the Rotterdam Transition Profile, except for education and
employment, significant differences were found between the three groups. A larger
proportion of young people with diabetes were in a more independent phase of
participation than those with ASD or CP. The wellbeing scores of those with
diabetes (median = 53, IQR: 47-58) and CP (median = 53, IQR: 48-60) were similar,
and significantly higher than for those with ASD (median = 47, IQR: 41-52; p <
0.001). CONCLUSIONS: Having established that our sample of young people with one
of three LTCs recruited close to transfer to adult services was representative,
we have described aspects of their satisfaction with services, participation and
wellbeing, noting similarities and differences by LTC. This information about
levels of current functioning is important for subsequent evaluation of the
impact of service features on the health and wellbeing of young people with LTCs
following transfer from child services to adult services.
PMID- 26424086
TI - A new protocol to accurately determine microtubule lattice seam location.
AB - Microtubules (MTs) are cylindrical polymers of alphabeta-tubulin that display
pseudo-helical symmetry due to the presence of a lattice seam of heterologous
lateral contacts. The structural similarity between alpha- and beta-tubulin makes
it difficult to computationally distinguish them in the noisy cryo-EM images,
unless a marker protein for the tubulin dimer, such as kinesin motor domain, is
present. We have developed a new data processing protocol that can accurately
determine alphabeta-tubulin register and seam location for MT segments. Our
strategy can deal with difficult situations, where the marker protein is
relatively small or the decoration of marker protein is sparse. Using this new
seam-search protocol, combined with movie processing for data from a direct
electron detection camera, we were able to determine the cryo-EM structures of MT
at 3.5 A resolution in different functional states. The successful distinction of
alpha- and beta-tubulin allowed us to visualize the nucleotide state at the E
site and the configuration of lateral contacts at the seam.
PMID- 26424087
TI - Contextual representations of negative images modulate intrusion frequency in an
intrusion provocation paradigm.
AB - BACKGROUND AND OBJECTIVES: To understand how memories of negative events become
highly accessible in the context of trauma, we tested the hypothesis that
contextual information modulates how easily intrusions can be provoked by
perceptual stimuli.. METHODS: Healthy participants viewed pictures depicting
trauma scenes either with or without accompanying moderate (i.e. survival,
recovery) or severe (i.e. fatality, permanent injury) outcome information. All
participants viewed the same depictions of trauma scenes. Involuntary memories
for the pictures were assessed using self-report diaries and an adapted version
of the Impact of Event Scales (IES). A blurred picture perceptual priming
paradigm was adapted to be used as an intrusion provocation task. RESULTS: The
severe outcome group experienced a significantly higher frequency of intrusions
on the intrusion provocation task in comparison to both moderate outcome and
control (no-context) conditions. The severe outcome condition did not increase
intrusions on the self-report diaries or the adapted IES. There was no effect of
condition on ratings for the emotionality, self-relevance, valence, or
seriousness of the trauma scenes. LIMITATIONS: The analogue method should not be
generalized directly to incidences of real-life trauma. It was unclear why
differences in intrusion frequency were found in the provocation task only. The
relative amount of individual conceptual and data-driven processing adopted by
the participants was not assessed. CONCLUSIONS: Manipulating contextual
information that determines the meaning of sensory-perceptual features for a
trauma scene can modulate subsequent intrusion frequency in response to visually
similar cues.
PMID- 26424088
TI - Glycosaminoglycans in subdural fluid and CSF after meningeal injury.
AB - BACKGROUND: Inflammatory mechanisms have an acknowledged role in the progression
of chronic subdural hematoma (CSDH) and in tissue response after subarachnoid
hemorrhage (SAH). The participation of extracellular matrix, especially
glycosaminoglycans, in the cellular events during tissue repair is known to be
important. We studied the production of glycosaminoglycans after two types of
meningeal injury-one caused by rupture of the dural border cell layer after head
injury, and the other caused by SAH. METHODS: Patients with CSDH (n = 28),
subdural effusion (n = 8), and SAH (n = 33) were included in the study. Samples
from subdural fluid or cerebrospinal fluid (CSF) were assayed for hyaluronic acid
(HA) with an enzyme-linked assay and for sulfated glycosaminoglycans (sGAGs) with
a dye-binding assay. RESULTS: The median HA concentration was 3021 (range, 408
14,012) ng/ml in the CSDH fluid, 668 (392-3607) ng/ml in the effusion fluid, and
21.7 (5.8-195) ng/ml in the serum. In lumbar CSF after SAH, the median HA
concentration was 246 (47-3686) ng/ml being 1.5-fold higher than that in control
CSF. The median sGAG concentration was 52.8 (0-144) MUg/ml in CSDH fluid, but
only 5.32 (0-20.5) MUg/ml in the effusion fluid, where the concentration was
similar to that in the serum. CONCLUSIONS: We found high, but variable,
concentrations of sGAGs and HA in the CSDH and effusion fluid after head injury
and HA in the CSF after SAH. Our results show that HA and sGAGs are induced after
meningeal injury and that these proteins may participate in a reactive process.
PMID- 26424090
TI - Carbapenem-Resistant Enterobacteriaceae: A Major Prevalence Difference due to the
High Performance of Carbapenemase Producers when compared to the Nonproducers.
PMID- 26424089
TI - MeSiC: A Model-Based Method for Estimating 5 mC Levels at Single-CpG Resolution
from MeDIP-seq.
AB - As the fifth base in mammalian genome, 5-methylcytosine (5 mC) is essential for
many biological processes including normal development and disease. Methylated
DNA immunoprecipitation sequencing (MeDIP-seq), which uses anti-5 mC antibodies
to enrich for methylated fraction of the genome, is widely used to investigate
methylome at a resolution of 100-500 bp. Considering the CpG density-dependent
bias and limited resolution of MeDIP-seq, we developed a Random Forest Regression
(RFR) model method, MeSiC, to estimate DNA methylation levels at single-base
resolution. MeSiC integrated MeDIP-seq signals of CpG sites and their surrounding
neighbors as well as genomic features to construct genomic element-dependent RFR
models. In the H1 cell line, a high correlation was observed between MeSiC
predictions and actual 5 mC levels. Meanwhile, MeSiC enabled to calibrate CpG
density-dependent bias of MeDIP-seq signals. Importantly, we found that MeSiC
models constructed in the H1 cell line could be used to accurately predict DNA
methylation levels for other cell types. Comparisons with methylCRF and MEDIPS
showed that MeSiC achieved comparable and even better performance. These
demonstrate that MeSiC can provide accurate estimations of 5 mC levels at single
CpG resolution using MeDIP-seq data alone.
PMID- 26424091
TI - Nicotine delivery, tolerability and reduction of smoking urge in smokers
following short-term use of one brand of electronic cigarettes.
AB - BACKGROUND: This randomized, partially single-blinded, 6-period crossover
clinical study of adult smokers compared the nicotine pharmacokinetics, impacts
on smoking urge and tolerability of various formulations of one brand of e
cigarettes with that of a tobacco cigarette. METHODS: Five e-cigarettes with
different e-liquid formulations containing 1.6 % and 2.4 % nicotine and a
conventional tobacco cigarette were randomized among 24 subjects under two
exposure sessions consisting of a 30-min controlled and a one-hour ad lib use
period to assess plasma nicotine levels, impacts on smoking urge and adverse
events. The 30-min controlled use session comprised an intensive use of the e
cigarettes with a total of 50 puffs taken every 30 s for comparison to a single
conventional cigarette having a typical machine-measured nicotine yield (~0.8
mg). Ad lib product use conditions provided insight into more naturalistic
product use behaviors and their accompanying smoking urge reductions. Adverse
events (AEs) were assessed by the Principal Investigator. RESULTS: Significant (p
< 0.05) increases in plasma nicotine concentrations occurred within 10 min of
controlled e-cigarette use and significant (p < 0.001) reductions from baseline
smoking urge were observed within 5 min. E-cigarette and cigarette nicotine
plasma levels were comparable for up to one hour of use. After both sessions (90
min), nicotine exposure was the highest for the cigarette, with all e-cigarettes
showing 23 % to 53 % lower plasma concentrations. During controlled use, peak
reduction in smoking urge for e-cigs occurred later than for the cigarette. After
completion of both sessions, significant smoking urge reduction persisted for
most of the tested e-cigarettes, albeit at levels lower than that provided by the
tobacco cigarette. Nicotine content, vehicle differences, and the presence of
menthol did not significantly affect smoking urge reduction by the e-cigarettes.
No subjects were discontinued due to AEs. The most frequently reported AEs events
included cough, throat irritation, headache, and dizziness. CONCLUSIONS: Blood
plasma nicotine levels obtained from short-term use of e-cigarettes containing
1.6 % and 2.4 % nicotine were significant, but lower than those of conventional
tobacco cigarettes, yet the reduction in craving symptoms were broadly
comparable. The types of AEs were consistent with other research studies of
longer duration that have reported that use of e-cigarettes by adult smokers is
well-tolerated. TRIAL REGISTRATION: http://ClinicalTrials.gov identifier:
NCT02210754 . Registered 8 August 2014.
PMID- 26424092
TI - In vitro inhibition of calcium oxalate crystallization and crystal adherence to
renal tubular epithelial cells by Terminalia arjuna.
AB - Urolithiasis is a multifactorial disease and remains a public health problem
around the world. Of all types of renal stones, calcium oxalate (CaOx) is the
most common composition formed in the urinary system of the patients with
urolithiasis. The present study is aimed at evaluating the antiurolithiatic
properties of the Tris-Cl extract (TE) of Terminalia arjuna (T. arjuna). The
antilithiatic activity of TE of T. arjuna was investigated on nucleation,
aggregation, and growth of the CaOx crystals, as well as its protective potency
was tested on oxalate-induced cell injury of NRK-52E renal epithelial cells.
Also, in vitro antioxidant activity of TE T. arjuna bark was also determined. The
TE of T. arjuna exhibited a concentration-dependent inhibition of nucleation and
growth of CaOx crystals. Inhibition of aggregation of CaOx crystals remains
constant. When NRK-52E cells were injured by exposure to oxalate for 48 h, the TE
prevented the cells from injury and CaOx crystal adherence resulting in increased
cell viability in a dose-dependent manner. The TE also scavenged the 2,2-diphenyl
1-picrylhydrazyl (DPPH) free radicals with an IC50 at 51.72 ug/mL. The results
indicated that T. arjuna is a potential candidate for phytotherapy against
urolithiasis as it attains the ability to inhibit CaOx crystallization and
scavenge DPPH free radicals in vitro along with a cytoprotective role.
PMID- 26424093
TI - Food handlers as potential sources of dissemination of virulent strains of
Staphylococcus aureus in the community.
AB - Food handlers may constitute a reservoir of virulent strains of Staphylococcus
aureus and may be vehicles of their transmission to food. One hundred and sixty
two volunteers were assessed for the presence of S. aureus on the hands and in
the nose. S. aureus was isolated by routine procedures, and the isolates were
tested for susceptibility against a panel of nine antimicrobial agents. The
isolates were further characterized by SmaI-PFGE profiling and the presence of
virulence factors. RESULTS: The prevalence of S. aureus was 19.8% in the nose and
11.1% on the hands; 6.2% of the individuals carried S. aureus both in their noses
and hands, and three individuals had the same strain (PFGE type) in the nose and
on the hands. Although 82% of the isolates were resistant to at least one
antibiotic, none demonstrated the presence of either mecA gene or resistance to
oxacillin (none identified as MRSA). Sixty-eight percent of the isolates from the
nose and hands possessed enterotoxin genes. This study revealed a high prevalence
of antibiotic resistance and virulence determinants among the isolates, including
not only classical and novel enterotoxin genes but also major virulence factors
such as tst. Potential dissemination of these strains in the community is a
matter of concern.
PMID- 26424094
TI - Does Oral Beta-Blocker Therapy Improve Long-Term Survival in ST-Segment Elevation
Myocardial Infarction With Preserved Systolic Function? A Meta-Analysis.
AB - BACKGROUND: The effect of oral beta-blocker therapy on long-term mortality in
patients with ST-segment elevation myocardial infarction (STEMI) who are treated
with primary percutaneous coronary intervention (PCI) and who have preserved left
ventricular ejection fraction (LVEF) remains unclear. METHODS: We searched
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for
studies evaluating the effect of oral beta-blocker therapy in patients with STEMI
who underwent primary PCI and who had preserved LVEF. The primary outcome was all
cause mortality. Randomized controlled trials and the observational studies that
reported an adjusted hazard ratio (or hazard ratio in the propensity score
matched patients) with follow-up duration equal to or more than 6 months were
included. Pooled hazard ratio with 95% confidence interval (CI) was calculated
using a random effect model. RESULTS: No randomized controlled trials met the
inclusion criteria. Seven observational studies totaling 10 857 patients met the
inclusion criteria. Follow-up duration ranged from 6 months to 5.2 years.
Preserved LVEF was defined as 40% in 4 studies and 50% in 3 studies. Based on the
pooled estimate, oral beta-blocker therapy was associated with a reduction in all
cause mortality (combined hazard ratio 0.79, 95% CI 0.65-0.97). CONCLUSION: This
meta-analysis demonstrates that oral beta-blocker therapy is associated with
decreased all-cause mortality in patients with STEMI who are treated with primary
PCI and who have preserved LVEF. This supports the current American College of
Cardiology Foundation/American Heart Association 2013 Guideline for the
Management of STEMI.
PMID- 26424095
TI - Treatment of CIA Mice with FGF21 Down-regulates TH17-IL-17 Axis.
AB - Recently, FGF21 was reported to play an important role in anti-inflammation. The
aim of the study is to explore the mechanism for FGF21 alleviating inflammation
of CIA. CIA mice were injected with FGF21 once a day for 28 days after first
booster immunization. The results showed that FGF21 alleviates arthritis severity
and decreases serum anti-CII antibodies levels in CIA mice. Compared with CIA
model, the number of the splenic TH17 cells was significantly decreased in FGF21
treated mice. FGF21 treatment reduced the mRNA expression of IL-17, TNF-alpha, IL
1beta, IL-6, IL-8, and MMP3 and increased level of IL-10 in the spleen tissue.
The expression of STAT3 and phosphorylated STAT3 was suppressed in FGF21-treated
group. The mRNA expression of RORgammat and IL-23 also decreased. In conclusion,
these findings suggest that the beneficial effects of FGF21 on CIA mice were
achieved by down-regulating Th17-IL-17 axis through STAT3/RORgammat pathway.
Modulating of Th17-mediated inflammatory response may be one of the mechanisms
for FGF21 attenuating inflammation in CIA.
PMID- 26424096
TI - Fli-1, a Functional Factor Performed in Autoimmune Lupus.
AB - Systemic lupus erythematosus (SLE) is an autoimmune disease. The friend leukemia
insertion site 1 (Fli-1) belongs to the Ets family of transcription factors.
Recent findings suggested that expression of Fli-1 was abnormal in SLE patients
and lupus mice. In addition, functional analysis indicated that Fli-1 plays a key
role in the development of this complex autoimmune disorder. Here, we review the
updated evidence indicating the roles of Fli-1 in autoimmune lupus. Hopefully,
the information obtained may result in a better understanding of the pathogenesis
of the systemic autoimmune disease.
PMID- 26424097
TI - Total Synthesis and Configurational Assignment of Ascospiroketal A.
AB - The total synthesis of the marine fungus-derived natural product ascospiroketal
is described. This concise synthesis relies on a unique Ag(I) -promoted tandem
cascade cyclization that provides direct access to the correctly configured
tricyclic core of the natural product from a linear precursor. The synthesis of
candidate stereostructures of ascospiroketal A allowed for the confident
assignment of both the relative and absolute stereochemistry of this unusual
octaketide.
PMID- 26424098
TI - Production of Optically Pure D-Lactic Acid by the Combined use of Weissella sp.
S26 and Bacillus sp. ADS3.
AB - Optically pure D-lactic acid was produced from glucose, xylose, or starch by the
combined use of Weissella sp. S26 and Bacillus sp. ADS3, two native bacterial
strains isolated from Singapore environment. Weissella sp. S26 was used to
ferment various sugars to lactic acid rich in D-isomer followed by sterilization
of the broth and inoculation of Bacillus sp. ADS3 cells to selectively degrade
acetic acid (if any) and L-lactic acid. In a simultaneous saccharification and
fermentation of starch by Weissella sp. S26 in 1 L of modified MRS medium
containing 50 g/L starch at 30 degrees C, lactic acid reached 24.2 g/L (23.6 g/L
of D-isomers and 0.6 g/L of L-isomers), and acetic acid was 11.8 g/L at 37 h. The
fermentation broth was sterilized at 100 degrees C for 20 min and cooled down to
30 degrees C followed by inoculation of Bacillus sp. ADS3 (10 %, v/v), and the
mixture was kept at 30 degrees C for 115 h. Acetic acid was completely removed,
and L-lactic acid was largely removed giving an optical purity of D-lactic acid
as high as 99.5 %.
PMID- 26424099
TI - [Experimental and therapeutic neuromodulation of emotion and social cognition
with non-invasive brain stimulation].
AB - Transcranial magnetic stimulation (TMS) is not only a highly elegant method for
basic neuroscientific research that employs transient lesions to explore the
relationship between brain structure and function but in a clinical context it is
also a very promising approach to augmentation therapy in middle to severe grade
depressive episodes. This overview illustrates the methodological basis of TMS
and illuminates its neuromodulatory potential with reference to findings from
recent studies on emotion regulation and social cognition. Against this empirical
background, it becomes clear that preclinical studies on healthy participants are
extremely important to develop innovative stimulation protocols and define
functionally relevant target regions to be tested in clinical studies for
therapeutic efficacy. Finally, the perspectives and limitations of functionally
guided, individualized TMS neuronavigation will be explored based on task
independent connectivity and task-dependent activity measurements.
PMID- 26424100
TI - Different effect of alcohol consumption on hypertension according to metabolic
health status.
AB - We aimed to investigate whether the effect of problematic alcohol drinking on
hypertension differed according to metabolic health statuses. Male participants
from the fifth Korea National Health and Nutrition Examination Survey were
recruited. Problematic alcohol drinkers were designated as subjects with heavy
drinking (?30 g per day), binge drinking (?7 glasses per day) or a high alcohol
use disorders identification test score (?20). Metabolically obese status was
defined as having ?1 or ?2 components of the diagnostic criteria for metabolic
syndrome, excluding the blood pressure component. Because the prevalence of
problematic alcohol drinking and the prevalence of hypertension largely differed
by age groups, separate analyses were performed for the two age groups (<50 and
?50 years). Among a total of 6329 subjects, 37.04% had hypertension. In the
younger age group, subjects with problematic alcohol drinking demonstrated a
higher prevalence of hypertension in both nonobese and obese individuals compared
with subjects who were nonobese and who were not problematic alcohol drinkers. Of
note, problematic alcohol drinking increased the risk of having hypertension ~3
times in young nonobese individuals who demonstrated a metabolically obese
phenotype compared with those who were metabolically healthy. However, metabolic
health status did not have a significant impact on the risk for having
hypertension in obese participants, regardless of their age groups. For the
prevention of hypertension, avoidance of problematic alcohol drinking should be
emphasized, especially in young subjects who show poor metabolic health status
despite being nonobese.
PMID- 26424101
TI - The significance of micro- and macrovascular biomarkers on cardiovascular outcome
in chronic kidney disease: a prospective cohort study.
AB - Measures of small and large artery dysfunction have not been investigated in a
single cohort for the prediction of cardiovascular (CV) events in patients with
nondialysed (ND) chronic kidney disease (CKD). This prospective cohort study
aimed to determine whether central pulse wave velocity (cPWV), central pulse
pressure (CPP) or microvascular post-occlusive reactive hyperaemia area (PORHHA)
independently predict CV events and mortality in CKD-ND. A total of 94 stage 1-5
CKD-ND (65.3+/-13.1 years; estimated glomerular filtration rate 35.3 (22.8-49.4)
ml min(-1) per 1.73 m(2)) patients were followed-up for a median of 52 (36-65)
months and had baseline cPWV and CPP measured by applanation tonometry and PORHHA
by laser Doppler flowmetry. Multiple failure time Cox regression models were used
to determine the predictive role of vascular parameters on CV mortality and
events. Based on multiple linear regressions, baseline age, diabetes, CV disease,
and systolic blood pressure (SBP) were independently related to cPWV (R(2)=0.3),
SBP and PORHHA to CPP (R(2)=0.45), whereas CPP was the only parameter
independently related to PORHHA (R(2)=0.16, all P<0.05). During follow-up, 41 CV
events occurred (14 CV deaths). In univariate analyses, cPWV (1.07 (1.02-1.13)
per m s(-1)), CPP (1.04 (1.01-1.07) per mm Hg) and lnPORHHA (0.70 (0.58-0.85) per
ln(PU * s)) were all related to the outcome. Baseline diabetes (HR 3.07 (1.65
5.68)), lnFGF23 (fibroblast growth factor-23; 1.86 (1.13-3.06) per RU ml(-1)) and
CPP (1.04 (1.01-1.07) per mm Hg) were independent predictors of CV events. The
impaired pulsatile component of large arteries (CPP) independently of other
vascular markers (cPWV, PORHHA) predicted CV outcomes in CKD-ND. CPP may
integrate the information provided by cPWV and PORHHA.
PMID- 26424102
TI - A HEALth Promotion and STRESS Management Program (HEAL-STRESS study) for
prehypertensive and hypertensive patients: a quasi-experimental study in Greece.
AB - Current hypertension guidelines advocate strategies encouraging healthy lifestyle
behaviours. So far, there is a paucity of studies for the efficacy of such
multifaceted programmes. The aim of this study is to investigate the efficacy of
an 8-week health-promotion programme for lowering blood pressure (BP) in
prehypertensive and hypertensive patients in the community. This was a quasi
experimental study using wait-list controls of 548 patients. The intervention
group was administered with an 8-week health-promotion intervention. Measurements
included home BP, smoking, body mass index (BMI), perceived stress, depression,
anxiety and Health Locus of Control. After adjusting for confounders, the
intervention group had a significant reduction in both systolic BP (SBP; mean
2.62 mm Hg, 95% confidence interval (CI): -1.29 to -3.96) and diastolic BP (DBP;
mean -1.0, 95% CI: -0.93 to -1.9) compared with controls. In all, 14.9% of
patients in the intervention group had >10 mm Hg reduction in SBP vs 4.4% in the
control group (P<0.001, numbers needed to treat (NNT)=10). With regards to DBP,
21.7% of patients in the intervention group had >5 mm Hg reduction vs 12.5% in
the control group (P=0.01, NNT=11). In terms of effect size, moderate-to-large
improvements of BMI, perceived stress, anxiety, depression, external and chance
Health Locus of Control were recorded. Changes in SBP and DBP were attributed to
BMI and depressive symptom reductions, respectively. Comprehensive non
pharmaceutical programmes for BP management are strongly encouraged. Their long
term benefits on cardiovascular morbidity and mortality remain to be established
by future research.
PMID- 26424103
TI - Identification of okadaic acid binding protein 2 in reconstituted sponge cell
clusters from Halichondria okadai and its contribution to the detoxification of
okadaic acid.
AB - Okadaic acid (OA) and OA binding protein 2 (OABP2) were previously isolated from
the marine sponge Halichondria okadai. Because the amino acid sequence of OABP2
is completely different from that of protein phosphatase 2A, a well-known target
of OA, we have been investigating the production and function of OABP2. In the
present study, we hypothesized that OABP2 plays a role in the detoxification of
OA in H. okadai and that the OA concentrations are in proportional to the OABP2
concentrations in the sponge specimens. Based on the OA concentrations and the
OABP2 concentrations in the sponge specimens collected in various places and in
different seasons, however, we could not determine a positive correlation between
OA and OABP2. We then attempted to determine distribution of OA and OABP2 in the
sponge specimen. When the mixture of dissociated sponge cells and symbiotic
species were separated with various pore-sized nylon meshes, most of the OA and
OABP2 was detected from the same 0-10 MUm fraction. Next, when sponge cell
clusters were prepared from a mixture of dissociated sponge cells and symbiotic
species in the presence of penicillin and streptomycin, we identified the 18S
rDNA of H. okadai and the gene of OABP2 in the analysis of genomic DNA but could
not detect OA by LC-MS/MS. We thus concluded that the sponge cells express OABP2,
and that OA was not apparently present in the sponge cells but could be
colocalized with OABP2 in the sponge cells at a concentration less than the limit
of detection.
PMID- 26424104
TI - Ambiguities and Asymmetries in Consent and Refusal: Reply to Manson.
AB - John Harris claims that is it 'palpable nonsense' to suggest that 'a child (or
anyone) might competently consent to a treatment but not be competent to refuse
it.' In 'Transitional Paternalism: How Shared Normative Powers Give Rise to the
Asymmetry of Adolescent Consent and Refusal' Neil Manson aims to explain away the
apparent oddness of this asymmetry of consent and refusal, by appealing to the
idea of shared normative powers, presenting joint bank accounts as an example. In
this article, I will argue that Manson's account fails to explain away the
oddness. Rather, I will argue that there are ambiguities to which Manson has not
paid sufficient attention. In fact, as odd as it may sound, I argue that Manson
actually agrees with Harris (at least in relation to the asymmetry of
competence). He fails to recognize that he agrees with Harris because he is not
careful enough to distinguish between different asymmetries, which I have
labelled the asymmetries of choice, permissibility and competence.
PMID- 26424105
TI - Effectiveness of an interactive platform, and the ESC/HFA heartfailurematters.org
website in patients with heart failure: design of the multicentre randomized e
Vita heart failure trial.
AB - AIMS: Electronic health support (e-health) may improve self-care of patients with
heart failure (HF). We aim to assess whether an adjusted care pathway with
replacement of routine consultations by e-health improves self-care as compared
with usual care. In addition, we will determine whether the ESC/HFA (European
Society of Cardiology/Heart Failure Association) website heartfailurematters.org
(HFM website) improves self-care when added to usual care. Finally, we aim to
evaluate the cost-effectiveness of these interventions. METHODS: A three-arm
parallel randomized trial will be conducted. Arm 1 consists of usual care; arm 2
consists of usual care plus the HFM website; and arm 3 is the adjusted care
pathway with an interactive platform for disease management (e-Vita platform),
with a link to the HFM website, which replaces routine consultations with HF
nurses at the outpatient clinic. In total, 414 patients managed in 10 Dutch HF
outpatient clinics or in general practice will be included and followed for 12
months. Participants are included if they have had an established diagnosis of HF
for at least 3 months. The primary outcome is self-care as measured by the
European Heart Failure Self-care Behaviour scale (EHFScB scale). Secondary
outcomes are quality of life, cardiovascular- and HF-related mortality,
hospitalization, and its duration as captured by hospital and general
practitioner registries, use of and user satisfaction with the HFM website, and
cost-effectiveness. PERSPECTIVE: This study will provide important prospective
data on the impact and cost-effectiveness of an interactive platform for disease
management and the HFM website. CLINICAL TRIAL REGISTRATION: unique identifier:
NCT01755988.
PMID- 26424106
TI - Supporting children's well-being: Outcomes of a rural child-focused education
program for separating or divorced parents.
PMID- 26424108
TI - Inflammatory Myopathy Causing Leg Pain in a Soccer Player: Case Report and Return
to-Play Considerations.
AB - Leg pain is a common condition in athletes as well as in the general population,
and has a broad differential diagnosis that includes musculoskeletal, vascular,
rheumatologic, and neurologic etiologies. Idiopathic inflammatory myopathy (IM)
is a relatively uncommon but recognized etiology of leg pain. In this case, we
describe an acute presentation of IM in an athlete resulting in leg pain and
activity limitation. The available literature suggests that moderate-intensity
exercise is safe and beneficial in idiopathic IM, but studies to date have not
assessed the effects of high-intensity exercise in IM or provided recommendations
for return to competitive contact sport in this population.
PMID- 26424107
TI - Effects of HIV and childhood trauma on brain morphometry and neurocognitive
function.
AB - A wide spectrum of neurocognitive deficits characterises HIV infection in adults.
HIV infection is additionally associated with morphological brain abnormalities
affecting neural substrates that subserve neurocognitive function. Early life
stress (ELS) also has a direct influence on brain morphology. However, the
combined impact of ELS and HIV on brain structure and neurocognitive function has
not been examined in an all-female sample with advanced HIV disease. The present
study examined the effects of HIV and childhood trauma on brain morphometry and
neurocognitive function. Structural data were acquired using a 3T Magnetom MRI
scanner, and a battery of neurocognitive tests was administered to 124 women: HIV
positive with ELS (n = 32), HIV-positive without ELS (n = 30), HIV-negative with
ELS (n = 31) and HIV-negative without ELS (n = 31). Results revealed significant
group volumetric differences for right anterior cingulate cortex (ACC), bilateral
hippocampi, corpus callosum, left and right caudate and left and right putamen.
Mean regional volumes were lowest in HIV-positive women with ELS compared to all
other groups. Although causality cannot be inferred, findings also suggest that
alterations in the left frontal lobe, right ACC, left hippocampus, corpus
callosum, left and right amygdala and left caudate may be associated with poorer
neurocognitive performance in the domains of processing speed, attention/working
memory, abstraction/executive functions, motor skills, learning and
language/fluency with these effects more pronounced in women living with both HIV
and childhood trauma. This study highlights the potential contributory role of
childhood trauma to brain alterations and neurocognitive decline in HIV-infected
individuals.
PMID- 26424110
TI - Gender-related drug effect on several markers of oxidation stress in diabetes
patients with and without complications.
AB - We previously reported that circulating lipid (malondialdehyde, MDA) and protein
oxidation (carbonyl residues, CO) products can be used as markers of risk for
complications in poorly controlled type 2 diabetics. Now, we aimed to evaluate
the existence of a gender effect on classical disease markers and oxidative
stress parameters and on the effectiveness of metformin and/or statins in
reducing CV risk in poorly controlled type 2 diabetics with and without
complications. Our results show that diabetics with complications had higher
plasma levels of FRAP, SOD and hs-CRP than those without complications, with FRAP
and SOD found increased in both genders. Interestingly, male and female patients
with complications had higher plasma levels of hs-CRP and MDA respectively, over
patients without complications. Multivariate analysis indicated metformin and
statin treatments effective in reducing plasma hs-CRP only in female and not in
male diabetics with complications. In these latter females, a positive
correlation between hs-CRP and triglycerides (TG) levels was found suggesting a
causal relationship between them. Statin treatment was effective in reducing MDA
in diabetics with complications irrespective of the gender. These data support
the addition of statins to diabetic standard therapy to control oxidation injury
and inflammation and, for the first time, indicate female patients with
complications more responsive than males to the CV protection offered by
metformin.
PMID- 26424111
TI - Human perivascular adipose tissue dysfunction as a cause of vascular disease:
Focus on vascular tone and wall remodeling.
AB - Obesity is one of the major risk factors for the development of cardiovascular
diseases. It is characterized by excessive or abnormal accumulation of adipose
tissue, including depots which surround the blood vessels named perivascular
adipose tissue (PVAT). PVAT plays endocrine and paracrine roles by producing
large numbers of metabolically vasoactive adipokines. The present review outlines
our current understanding of the beneficial roles of PVAT in vascular tone and
remodeling in healthy subjects supported by clinical studies, highlighting
different factors or mechanisms that could mediate protective effects of PVAT on
vascular function. Most studies in humans show that adiponectin is the best
candidate for the advantageous effect of PVAT. However, in pathological
conditions especially obesity-related cardiovascular diseases, the beneficial
effects of PVAT on vascular functions are impaired and transform into detrimental
roles. This change is defined as PVAT dysfunction. In the current review, the
contribution of PVAT dysfunction to obesity-related cardiovascular diseases has
been discussed with a focus on possible mechanisms including an imbalance between
beneficial and detrimental adipokines (commonly described as decreased levels of
adiponectin and increased levels of leptin or tumor necrosis factor-alpha
(TNFalpha)), increased quantity of adipose tissue, inflammation, cell
proliferation and endothelial dysfunction. Finally, novel pharmacotherapeutic
targets for the treatment of cardiovascular and metabolic disorders are
addressed.
PMID- 26424112
TI - Suture, synthetic, or biologic in contaminated ventral hernia repair.
AB - BACKGROUND: Data are lacking to support the choice between suture, synthetic
mesh, or biologic matrix in contaminated ventral hernia repair (VHR). We
hypothesize that in contaminated VHR, suture repair is associated with the lowest
rate of surgical site infection (SSI). METHODS: A multicenter database of all
open VHR performed at from 2010-2011 was reviewed. All patients with follow-up of
1 mo and longer were included. The primary outcome was SSI as defined by the
Centers for Disease Control and Prevention. The secondary outcome was hernia
recurrence (assessed clinically or radiographically). Multivariate analysis
(stepwise regression for SSI and Cox proportional hazard model for recurrence)
was performed. RESULTS: A total of 761 VHR were reviewed for a median (range)
follow-up of 15 (1-50) mo: there were 291(38%) suture, 303 (40%) low-density
and/or mid-density synthetic mesh, and 167(22%) biologic matrix repair. On
univariate analysis, there were differences in the three groups including
ethnicity, ASA, body mass index, institution, diabetes, primary versus incisional
hernia, wound class, hernia size, prior VHR, fascial release, skin flaps, and
acute repair. The unadjusted outcomes for SSI (15.1%; 17.8%; 21.0%; P = 0.280)
and recurrence (17.8%; 13.5%; 21.5%; P = 0.074) were not statistically different
between groups. On multivariate analysis, biologic matrix was associated with a
nonsignificant reduction in both SSI and recurrences, whereas synthetic mesh
associated with fewer recurrences compared to suture (hazard ratio = 0.60; P =
0.015) and nonsignificant increase in SSI. CONCLUSIONS: Interval estimates
favored biologic matrix repair in contaminated VHR; however, these results were
not statistically significant. In the absence of higher level evidence, surgeons
should carefully balance risk, cost, and benefits in managing contaminated
ventral hernia repair.
PMID- 26424113
TI - Following the money: Mapping the sources and funding flows of alcohol and other
drug treatment in Australia.
AB - INTRODUCTION AND AIMS: The structures of health systems impact on patient
outcomes. We present and analyse the first detailed mapping of who funds alcohol
and other drug (AOD) treatment and the channels and intermediaries through which
funding flows from the funding sources to treatment providers. DESIGN AND
METHODS: The study involved a literature review of AOD treatment financing and
existing diagrammatic representations of the structure of the Australian health
system. We interviewed 190 key informants to particularise the AOD treatment
sector, and undertook two case examples of government funded non-government
organisations providing AOD treatment. RESULTS: Funding sources include the
Australian and state and territory governments, philanthropy, fund-raising and
clients themselves. While funding sources align with the health sector generally
and the broader social services sector, the complexity of flows from source to
treatment service and the number of intermediaries are noteworthy. So too are the
many sources of funding drawn on by some treatment providers. Diversification is
both beneficial and disadvantageous for non-government treatment providers,
adding to administrative workloads, but smoothing the risk of funding shortfalls.
Government funders benefit from sharing risk. DISCUSSION AND CONCLUSIONS:
Circuitous funding flows multiply the funding sources drawn on by services and
put distance between the funding source and the service provider. This leads to
concerns over lack of transparency about what is being purchased and challenges
for the multiply funded service provider in maintaining programs and service
models amid multiple and sometimes competing funding and accountability
frameworks. [Chalmers J, Ritter A, Berends L, Lancaster K. Following the money:
Mapping the sources and funding flows of alcohol and other drug treatment in
Australia. Drug Alcohol Rev 2016;35:255-262].
PMID- 26424109
TI - NADPH oxidases-do they play a role in TRPC regulation under hypoxia?
AB - In the lung, acute alveolar hypoxia causes hypoxic pulmonary vasoconstriction
(HPV) to maintain ventilation perfusion matching and thus optimal oxygenation of
blood. In contrast, global chronic hypoxia triggers a pathological thickening of
pulmonary arterial walls, called pulmonary vascular remodelling, leading to
persistence of pulmonary hypertension (PH). Moreover, ischaemia or hypoxia can
lead to a damage of pulmonary endothelial cells with subsequent oedema formation.
Alterations in reactive oxygen species (ROS) have been suggested as a crucial
mediator of such responses. Among the various sources of cellular ROS production,
NADPH oxidases (NOXs) have been found to contribute to these physiological and
pathophysiological signalling processes. NOXs are the only known examples that
generate ROS as the primary function of the enzyme system. However, the
downstream targets of NOX-derived ROS signalling in hypoxia are still not known.
Canonical transient receptor potential (TRPC) channels recently have been
recognised as directly or indirectly ROS-activated channels and have been shown
to be essential for hypoxia-dependent vascular regulatory processes in the lung.
Against this background, we here summarise the current knowledge on NOX-mediated
TRPC channel signalling during hypoxia in the pulmonary circulation.
PMID- 26424114
TI - FGF9-induced changes in cellular redox status and HO-1 upregulation are FGFR
dependent and proceed through both ERK and AKT to induce CREB and Nrf2
activation.
AB - Our previous studies demonstrated that fibroblast growth factor 9 (FGF9) protects
cortical and dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP(+))
induced oxidative insult by upregulation of gamma-glutamylcysteine synthetase
(gamma-GCS) and heme oxygenase-1 (HO-1). However, the mechanisms responsible for
FGF9-induced gamma-GCS and HO-1 upregulation remain uncharacterized. In the
present study, we demonstrate the signaling pathways by which FGF9 upregulates HO
1 and gamma-GCS expression. We found that FGF9-induced HO-1 and gamma-GCS
expression was prevented by PD173014, an inhibitor of the FGF receptor (FGFR).
FGF9 treatment induced the phosphorylation of FGFR downstream signals of
extracellular signal-regulated kinase 1/2 (ERK1/2) and AKT in a dose- and time
dependent manner. The inhibition of MEK/ERK1/2 or PI3K/AKT activity by U0126 or
wortmannin, but not the inhibition of phospholipase Cgamma by U73122, prevented
FGF9-induced gamma-GCS and HO-1 upregulation, changes in cellular redox status,
and neuroprotection against MPP(+) toxicity in primary cortical and dopaminergic
neurons. Furthermore, FGF9 treatment enhanced the promoter activity of the cAMP
response element binding protein (CREB) and nuclear factor erythroid-derived 2
like 2 (Nrf2), and this phenomenon was blocked by PD173014 or U0126 or
wortmannin. Knockdown of CREB and Nrf2 by shRNA blocked FGF9-induced gamma-GCS
and HO-1 upregulation, but not ERK and AKT phosphorylation. An in vivo study
consistently showed that FGF9 overexpression using a lentivirus delivery system
induced ERK1/2 phosphorylation and HO-1 upregulation and protected dopaminergic
neurons against MPP(+) toxicity in rat substantia nigra. These results indicate
that FGF9-induced HO-1 and gamma-GCS upregulation is mediated by binding to FGFR
and activation of two parallel downstream signaling pathways, ERK and AKT, which
reconverge to induce CREB and Nrf2 transcriptional activity.
PMID- 26424115
TI - Sound envelope processing in the developing human brain: A MEG study.
AB - OBJECTIVE: This study investigated auditory cortical processing of linguistically
relevant temporal modulations in the developing brains of young children.
METHODS: Auditory envelope following responses to white noise amplitude modulated
at rates of 1-80 Hz in healthy children (aged 3-5 years) and adults were recorded
using a paediatric magnetoencephalography (MEG) system and a conventional MEG
system, respectively. RESULTS: For children, there were envelope following
responses to slow modulations but no significant responses to rates higher than
about 25 Hz, whereas adults showed significant envelope following responses to
almost the entire range of stimulus rates. CONCLUSION: Our results show that the
auditory cortex of preschool-aged children has a sharply limited capacity to
process rapid amplitude modulations in sounds, as compared to the auditory cortex
of adults. SIGNIFICANCE: These neurophysiological results are consistent with
previous psychophysical evidence for a protracted maturational time course for
auditory temporal processing. The findings are also in good agreement with
current linguistic theories that posit a perceptual bias for low frequency
temporal information in speech during language acquisition. These insights also
have clinical relevance for our understanding of language disorders that are
associated with difficulties in processing temporal information in speech.
PMID- 26424117
TI - Ebola and HIV: managing febrile times.
PMID- 26424116
TI - Structural brain alterations in hemifacial spasm: A voxel-based morphometry and
diffusion tensor imaging study.
AB - OBJECTIVE: Hemifacial spasm (HFS) is characterized by involuntary, irregular
clonic or tonic movement of muscles innervated by the facial nerve. We evaluated
structural reorganization in brain gray matter and white matter and whether
neuroplasticity is linked to clinical features in HFS patients. METHODS: High
resolution structural magnetic resonance imaging and diffusion tensor imaging
data were acquired by 3.0 T MRI from 42 patients with HFS and 30 healthy
subjects. The severity of the spasm was assessed according to Jankovic disability
rating scale. Voxel-based morphometry (VBM) and tract-based spatial statistics
(TBSS) analysis were performed to identify regional grey matter volume (GMV)
changes and whole-brain microstructural integrity disruption measured by
fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and
radial diffusivity (RD). RESULTS: The VBM analysis showed that patients with HFS
reduced GMV in the right inferior parietal lobule and increased GMV in the
cerebellar lobule VIII, when compared with healthy subjects. Furthermore, within
the HFS disease group, GMV decreased with the disease duration in the right
inferior parietal lobule. TBSS did not identify group differences in diffusivity
parameters. CONCLUSIONS: While no white matter integrity disruption was detected
in the brain of patients with HFS, our study identified evident GMV changes in
brain areas which were known to be involved in motor control. SIGNIFICANCE: Our
results suggest that HFS, a chronic neurovascular conflict disease, is related to
structural reorganization in the brain.
PMID- 26424118
TI - Panobinostat clinical trial highlights the challenges towards an HIV cure.
PMID- 26424120
TI - Temporal trends in prognostic markers of HIV-1 virulence and transmissibility: an
observational cohort study.
AB - BACKGROUND: Measures of CD4 T-cell count and HIV-1 plasma viral load before
antiretroviral therapy are proxies for virulence. Whether these proxies are
changing over time has implications for prevention and treatment. The aim of this
study was to investigate those trends. METHODS: Data were derived from the
Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE)
collaboration of mainly European seroconverter cohorts. Longitudinal CD4 cell
counts and plasma viral load measurements before the initiation of antiretroviral
therapy or AIDS onset were analysed by use of linear or fractional polynomials
mixed models adjusting for all available potential confounders. Calendar time
effects were modelled through natural cubic splines. FINDINGS: 15 875 individuals
seroconverting from 1979 to 2008 fulfilled the inclusion criteria; 3215 (20.3%)
were women; median follow-up was 31 months (IQR 14-62); dropout before starting
antiretroviral therapy or AIDS onset was 8.1%. Estimated CD4 counts at
seroconversion for a typical individual declined from about 770 cells per MUL
(95% CI 750-800) in the early 1980s to a plateau of about 570 cells per MUL (555
585) after 2002. CD4 cell rate of loss increased up to 2002. Estimated set-point
plasma viral loads increased from 4.05 log10 copies per mL (95% CI 3.98-4.12) in
1980 to 4.50 log10 copies per mL (4.45-4.54) in 2002 with a tendency of returning
to lower loads thereafter. Results were similar when we restricted analyses to
various subsets, including adjusting for plasma viral load assay, censored follow
up at 3 years, or used variations of the main statistical approach.
INTERPRETATION: Our results provide strong indications of increased HIV-1
virulence and transmissibility during the course of the epidemic and a potential
plateau effect after about 2002. FUNDING: European Union Seventh Framework
Programme.
PMID- 26424121
TI - The first step on the continuum of care.
PMID- 26424119
TI - Interventions to promote adherence to antiretroviral therapy in Africa: a network
meta-analysis.
AB - BACKGROUND: Adherence to antiretroviral therapy (ART) is necessary for the
improvement of the health of patients and for public health. We sought to
determine the comparative effectiveness of different interventions for improving
ART adherence in HIV-infected people living in Africa. METHODS: We searched for
randomised trials of interventions to promote antiretroviral adherence within
adults in Africa. We searched AMED, CINAHL, Embase, Medline (via PubMed), and
ClinicalTrials.gov from inception to Oct 31, 2014, with the terms "HIV", "ART",
"adherence", and "Africa". We created a network of the interventions by pooling
the published and individual patients' data for comparable treatments and
comparing them across the individual interventions with Bayesian network meta
analyses. The primary outcome was adherence defined as the proportion of patients
meeting trial defined criteria; the secondary endpoint was viral suppression.
FINDINGS: We obtained data for 14 randomised controlled trials, with 7110
patients. Interventions included daily and weekly short message service (SMS;
text message) messaging, calendars, peer supporters, alarms, counselling, and
basic and enhanced standard of care (SOC). Compared with SOC, we found
distinguishable improvement in self-reported adherence with enhanced SOC (odds
ratio [OR] 1.46, 95% credibility interval [CrI] 1.06-1.98), weekly SMS messages
(1.65, 1.25-2.18), counselling and SMS combined (2.07, 1.22-3.53), and treatment
supporters (1.83, 1.36-2.45). We found no compelling evidence for the remaining
interventions. Results were similar when using viral suppression as an outcome,
although the network contained less evidence than that for adherence. Treatment
supporters with enhanced SOC (1.46, 1.09-1.97) and weekly SMS messages (1.55,
1.01-2.38) were significantly better than basic SOC. INTERPRETATION: Several
recommendations for improving adherence are unsupported by the available
evidence. These findings can inform future intervention choices for improving ART
adherence in low-income settings. FUNDING: None.
PMID- 26424122
TI - Network meta-analyses: powerful but not without perils.
PMID- 26424123
TI - The HIV care continuum in black MSM in the USA.
PMID- 26424124
TI - The changing virulence of HIV.
PMID- 26424125
TI - Large-Scale Conformational Dynamics Control H5N1 Influenza Polymerase PB2 Binding
to Importin alpha.
AB - Influenza A RNA polymerase complex is formed from three components, PA, PB1, and
PB2. PB2 is independently imported into the nucleus prior to polymerase
reconstitution. All crystallographic structures of the PB2 C-terminus (residues
536-759) reveal two globular domains, 627 and NLS, that form a tightly packed
heterodimer. The molecular basis of the affinity of 627-NLS for importins
remained unclear from these structures, apparently requiring large-scale
conformational changes prior to importin binding. Using a combination of solution
state NMR, small-angle neutron scattering, small-angle X-ray scattering (SAXS),
and Forster resonance energy transfer (FRET), we show that 627-NLS populates a
temperature-dependent dynamic equilibrium between closed and open states. The
closed state is stabilized by a tripartite salt bridge involving the 627-NLS
interface and the linker, that becomes flexible in the open state, with 627 and
NLS dislocating into a highly dynamic ensemble. Activation enthalpies and
entropies associated with the rupture of this interface were derived from
simultaneous analysis of temperature-dependent chemical exchange saturation
transfer measurements, revealing a strong temperature dependence of both open
state population and exchange rate. Single-molecule FRET and SAXS demonstrate
that only the open-form is capable of binding to importin alpha and that, upon
binding, the 627 domain samples a dynamic conformational equilibrium in the
vicinity of the C-terminus of importin alpha. This intrinsic large-scale
conformational flexibility therefore enables 627-NLS to bind importin through
conformational selection from a temperature-dependent equilibrium comprising both
functional forms of the protein.
PMID- 26424127
TI - A telephone interview version of the middle childhood HOME Observation
Measurement of the Environment.
AB - BACKGROUND: The Home Observation Measurement of the Environment (HOME) is a 59
item observation and interview tool used to measure how suitable a child's home
is for a child of his or her developmental age and has been used extensively in
research. The HOME is usually performed in the child's home, which has cost
implications. We wished to develop a telephone version of the HOME. METHODS: We
developed a 54-item telephone interview version of the HOME and used it to
measure the home environment in 77 children aged 6-10 years inclusive attending a
child and adolescent mental health clinic, followed by a home visit and HOME
assessment. The results of the telephone home assessment were then compared with
the results of the original HOME. RESULTS: Our sample had a mean HOME score of
47.6, standard deviation (SD) = 5.5 and a mean telephone home score of 42.6, SD =
5.1. No difference was found in comparison of the subscale mean scores of the
HOME with the telephone home assessment. The agreement of 54 items in common
between the HOME and telephone home assessment ranged from 73% agreement to 100%
agreement. Forty-three of 50 items had moderate to almost perfect agreement using
kappa analysis (kappa = 0.41-0.99); three had 100% agreement. CONCLUSIONS: The
telephone version of the HOME compares favourably with the HOME.
PMID- 26424126
TI - Cubical Shape Enhances the Interaction of Layer-by-Layer Polymeric Particles with
Breast Cancer Cells.
AB - Blood-borne objects display a nonspherical shape with in-flow dimensions much
larger than the vascular endothelial fenestrations, yet, at the diseased state,
are able to traverse through these fenestrations owing to their elasticity. The
role of physical parameters including shape and elasticity in the behavior of
objects found in the tumor microenvironment needs to be understood to ultimately
enhance chemotherapy and minimize its side effects. In this study, sphere- and
cube-shaped biocompatible elastic microparticles (EM) made via layer-by-layer
assembly of hydrogen-bonded tannic acid/poly(N-vinylpyrrolidone) (TA/PVPON) as
hollow polymer shells and their rigid core-shell precursors (RM) are explored. In
contrast to rigid five-bilayer (TA/PVPON) core shells, hollow elastic shells are
unrecognized by J774A.1 macrophages, yet interact with endothelial and breast
cancer cells. Internalization of cubical shells is fivefold more efficient by
HMVEC (human microvascular endothelial cells) and sixfold and 2.5-fold more
efficient by MDA-MB-231 and by SUM159 (breast cancer cells), respectively,
compared to spherical shells. The interaction of cubical (TA/PVPON)5 shells with
endothelial cells is similar under 10 s(-1) (characteristic of tumor vasculature)
and 100 s(-1) shear rate (normal vasculature) while it is decreased at 100 s(-1)
shear rate for the spherical shells. Our data suggest that cubical geometry
promotes interaction of particles with breast cancer cells, while elasticity
prevents engulfment by phagocytic cells in the tumor microenvironment.
PMID- 26424128
TI - Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on
peripheral B-cell subsets with clinical manifestations in systemic lupus
erythematosus.
AB - OBJECTIVE: B-cell-activating factor (BAFF) and a proliferation-inducing ligand
(APRIL) signaling pathways regulate B-cell survival through interactions with
their receptors BAFF-R, TACI and BCMA. We evaluated the association of these
ligands/receptors on B-cell subsets according to clinical manifestations of
systemic lupus erythematosus (SLE). METHODS: BAFF and APRIL serum concentrations
were measured in 30 SLE patients by enzyme-linked immunosorbent assay. The BAFF
R, TACI and BCMA expression was analyzed on each B cell subset (CD19 + CD27-CD38
/ + naive; CD19 + CD27 + CD38-/ + memory; CD19 + CD27-CD38 + + immature and CD19
+ CD27 + CD38 + + plasma cells) by flow cytometry, and compared among patients
with different clinical manifestations as well as healthy controls (HCs).
RESULTS: Serum BAFF and APRIL levels were high in SLE patients and correlated
with the Mex-SLEDAI disease activity index (r = 0.584; p = 0.001 and r = 0.456; p
= 0.011, respectively). The SLE patients showed an increased proportion of memory
and plasma B cells (p < 0.05). BAFF-R, TACI and BCMA expression in SLE patients
was decreased in almost all B cell subsets compared to HCs (p < 0.05). A lower
BCMA expression was associated with severe disease activity, glomerulonephritis,
serositis and hemolytic anemia (p < 0.01). BCMA expression showed a negative
correlation with Mex-SLEDAI score (r = -0.494, p = 0.006). CONCLUSIONS: Decreased
BCMA expression on peripheral B cells according to severe disease activity
suggests that BCMA plays an important regulating role in B-cell hyperactivity and
immune tolerance homeostasis in SLE patients.
PMID- 26424129
TI - Low bone mass and carotid atherosclerosis in lupus erythematosus patients from
Granada, a city in the south of Spain.
PMID- 26424131
TI - Effect of sesamin against cytokine production from influenza type A H1N1-induced
peripheral blood mononuclear cells: computational and experimental studies.
AB - In 2009, swine flu (H1N1) had spread significantly to levels that threatened
pandemic influenza. There have been many treatments that have arisen for patients
since the WHO first reported the disease. Although some progress in controlling
influenza has taken place during the last few years, the disease is not yet under
control. The development of new and less expensive anti-influenza drugs is still
needed. Here, we show that sesamin from the seeds of the Thai medicinal plant
Sesamum indicum has anti-inflammatory cytokines in human peripheral blood
mononuclear cells (PBMCs) induced by 2009 influenza virus type A H1N1. In this
study, the combinatorial screening method combined with the computational
approach was applied to investigate the new molecular binding structures of
sesamin against the 2009 influenza virus type A H1N1 (p09N1) crystallized
structure. Experimental methods were applied to propose the mechanisms of sesamin
against cytokine production from H1N1-induced human PBMC model. The molecular
dynamics simulation of sesamin binding with the p09N1 crystallized structure
showed new molecular binding structures at ARG118, ILE222, ARG224, and TYR406,
and it has been proposed that sesamin could potentially be used to produce anti
H1N1 compounds. Furthermore, the mechanisms of sesamin against cytokine
production from influenza type A H1N1-induced PBMCs by ELISA and signaling
transduction showed that sesamin exhibits the ability to inhibit proinflammatory
cytokines, IL-1beta and TNF-alpha, and to enhance the activity of the immune cell
cytokine IL-2 via downregulating the phosphorylated JNK, p38, and ERK1/2 MAPK
signaling pathways. This information might very well be useful in the prevention
and treatment of immune-induced inflammatory disorders.
PMID- 26424132
TI - The role of microRNA-1 and microRNA-206 in the proliferation and differentiation
of bovine skeletal muscle satellite cells.
AB - MicroRNAs (miRNAs) have been found to play essential roles in muscle cell
proliferation and differentiation. MicroRNA-1 (miR-1) and microRNA-206 (miR-206),
which are similar and have the same seed sequence, have specific roles in
modulating skeletal muscle proliferation and differentiation in vitro and in
vivo. However, there is no information about their function during bovine
skeletal muscle satellite cell development. In this study, the profiles of miR-1
and miR-206 and their biological functions in bovine skeletal muscle cell
development was investigated. The target genes were predicted, and we used a dual
luciferase reporter assay to demonstrate that miR-1 and miR-206 directly targeted
the 3' untranslated region (3'UTR) of paired-box transcription factor Pax7 and
histone deacetylase 4 (HDAC4). We showed that miR-1 and miR-206 facilitate bovine
skeletal muscle satellite cell myogenic differentiation by restricting the
expression of their target gene and that inhibition of miR-1 and miR-206
increased the Pax7 and HDAC4 protein levels and substantially enhanced satellite
cell proliferation. Therefore, our results revealed the mechanism in which miR-1
and miR-206 positively regulate bovine skeletal muscle satellite cell myogenic
differentiation via Pax7 and HDAC4 downregulation.
PMID- 26424133
TI - RETROSPECTIVE METHOD VALIDATION AND UNCERTAINTY ESTIMATION FOR ACTINIDES
DETERMINATION IN EXCRETA BY ALPHA SPECTROMETRY.
AB - Two essential technical requirements of ISO 17025 guide for accreditation of
testing and calibration laboratories are the validation of methods and the
estimation of all sources of uncertainty that may affect the analytical result.
Bioelimination Laboratory from Radiation Dosimetry Service of CIEMAT (Spain) uses
alpha spectrometry to quantify alpha emitters (Pu, Am, Th, U and Cm isotopes) in
urine and faecal samples from workers exposed to internal radiation. Therefore
and as a step previous to achieving the ISO 17025 accreditation, the laboratory
has performed retrospective studies based on the obtained results in the past few
years to validate the analytical method. Uncertainty estimation was done
identifying and quantifying all the contributions, and finally the overall
combined standard uncertainty was calculated.
PMID- 26424134
TI - RADON AND PROGENY SOURCED DOSE ASSESSMENT OF SPA EMPLOYEES IN BALNEOLOGICAL
SITES.
AB - This study was conducted in the scope of IAEA project with the name 'Establishing
a Systematic Radioactivity Survey and Total Effective Dose Assessment in Natural
Balneological Sites' (TUR/9/018), at the Health Physics department of Saraykoy
Nuclear Research and Training Center (SANAEM). The aim of this study is
estimation of radon and progeny sourced effective dose for the people who are
working at the spa facilities by measuring radon activity concentration (RAC) at
the ambient air of indoor spa pools and dressing rooms. As it is known, the
source of the radon gas is the radium content of the earth crust. Therefore,
thermal waters coming from ground may contain dissolved radon and the radon can
diffuse water to air. So the ambient air of spa pools can contain serious RAC
that depends on a lot of parameters. In this regard, RAC measurements were
executed at the 70 spa facilities in Turkey. The measurements were done with both
active and passive methods at ambient air of spa pools and dressing rooms. Thus,
active measurements were carried out by using the Alphaguard((r)) with diffusion
mode during half an hour, and passive measurements were carried out by using the
humidity resistive CR-39 radon detectors during 2 months. Results show that RAC
values at ambient air of spa pools varies between 13 Bq m(-3) and 10 kBq m(-3)
Because long-term measurements are more reliable, if it is available, for dose
calculations passive radon measurements (with CR-39 detectors) at ambient air of
spa pools and dressing rooms were used, otherwise active measurement results were
used. With the measurement by the conversion coefficients of ICRP 65 and
occupational data of the employees has got from questionary forms, effective dose
values were calculated. According to the calculations, spa employees are exposed
to annual average dose between 0.05 and 29 mSv because of radon and progeny.
PMID- 26424135
TI - PROPERTIES OF THE BEOSL DOSIMETRY SYSTEM IN THE FRAMEWORK OF A LARGE-SCALE
PERSONAL MONITORING SERVICE.
AB - The Individual Monitoring Service of the Helmholtz Zentrum Munchen is currently
using the BeOSL dosimetry system for monitoring ~15 000 persons per month. This
dosimetry system has a modular structure and represents a complete new concept on
handling dosemeters in a large-scale dosimetry service. It is based on optically
stimulated luminescence dosemeters made of beryllium oxide. The dosimetric and
operational properties of the system are shown and discussed.
PMID- 26424136
TI - CORRECTIONS ASSOCIATED WITH ON-PHANTOM CALIBRATIONS OF NEUTRON PERSONAL
DOSEMETERS.
AB - The response of neutron personal dosemeters as a function of neutron energy and
angle of incidence is typically measured by mounting the dosemeters on a slab
phantom and exposing them to neutrons from an accelerator-based or radionuclide
source. The phantom is placed close to the source (75 cm) so that the effect of
scattered neutrons is negligible. It is usual to mount several dosemeters on the
phantom together. Because the source is close, the source distance and the
neutron incidence angle vary significantly over the phantom face, and each
dosemeter may receive a different dose equivalent. This is particularly important
when the phantom is angled away from normal incidence. With accelerator-produced
neutrons, the neutron energy and fluence vary with emission angle relative to the
charged particle beam that produces the neutrons, contributing further to
differences in dose equivalent, particularly when the phantom is located at other
than the straight-ahead position (0 degrees to the beam). Corrections for these
effects are quantified and discussed in this article.
PMID- 26424137
TI - NATIONAL DOSE REGISTER IN FRANCE WITHIN THE NATIONAL INFORMATION SYSTEM SISERI.
AB - Over the past decade, France has developed an electronic dose register at
national level called SISERI. Institute for Radiological Protection and Nuclear
Safety is in charge of the management of this information system. Besides the
main purpose of being a central register of any doses measured for the individual
dosimetric monitoring of all exposed workers, SISERI has been developed so as to
constitute a tool for occupational physicians and radiation protection officers
allowing access in real-time to the results of the individual monitoring. The
SISERI information system centralises, verifies and keeps the records of all
personal dosimetric results of the 370 000 workers annually monitored in France.
Moreover, since the publication of a new order in 2013, employers shall declare
any new workers in SISERI before the beginning of their occupation and they shall
upload data concerning in particular the activity field/sector and the occupation
of each worker. The enforcement of this new order is going to enrich the
individual dosimetric information stored in SISERI. Thus, it is expected that
more precise and accurate statistics on occupational exposure to ionising
radiation in France will be established in the next few years.
PMID- 26424138
TI - ESTABLISHMENT OF A NATIONAL DOSE REGISTER AND A DOSIMETRY SERVICE APPROVAL SYSTEM
IN IRELAND.
AB - Until the end of 2012, the Radiological Protection Institute of Ireland (RPII)
operated a personal dosimetry service for workers in the medical, industrial,
education and research sectors in Ireland. The data recorded by the RPII service
were used to generate national dose statistics and as such acted as a National
Dose Register (NDR). In preparation for the closure of the RPII dosimetry service
in 2012, a formal NDR was introduced for the first time in Ireland and data on
all monitored workers are now supplied to it annually by Approved Dosimetry
Services. A new system for approving dosimetry services operating in Ireland was
also introduced in 2012. The criteria for approval are based on the
recommendations given in the European Commission's publication, 'Radiation
Protection No. 160'. This paper describes the steps involved and the operational
experience gained in establishing both the NDR and the system for approval of
dosimetry services.
PMID- 26424139
TI - Environmental Isolate of Rahnella aquatilis Harbors Class 1 Integron.
AB - The paper presents first description of class 1 integron in an environmental
strain of Rahnella aquatilis, a rarely isolated Gram-negative bacterium of the
family Enterobacteriaceae. The strain was isolated from the Warta river water,
Poland. Class 1 integrase gene was detected by a PCR assay. Sequencing of the
integron's variable region showed the presence of a dfrA1-aadA1 gene cassette
array. The integron was located in a 54-kbp plasmid that was transferable to
Escherichia coli J-53 recipient strain in a conjugation assay. The integron
bearing R. aquatilis strain was resistant to aminoglycosides, penicillins,
trimethoprim, sulfamethoxazole, and trimethoprim/sulfamethoxazole. This paper
confirms that water environment play a major role in the spread of integrons and,
consequently, antimicrobial resistance, among bacteria of various genera.
PMID- 26424140
TI - Bacterial Diversity in Bohai Bay Solar Saltworks, China.
AB - The microbiota in solar salterns plays an important role in salt production
quantitatively and qualitatively. Bohai Bay coast is the major sea salt producing
area in China. However, few ecological characterization studies of the Bohai Bay
salt ponds, particularly of their microbial diversity, have been conducted. This
study investigated the structure and diversity of the bacterial community in
Hangu saltworks in response to environmental factors. The brine water was sampled
from five selected saltponds within a salinity range of 5.0-19.3% in May, July,
and October, 2012. Phylogenetic analysis based on the denaturing gradient gel
electrophoresis (DGGE) patterns of the PCR-amplified 16S rRNA gene fragment
showed that, rather than pond salinity, especially the month of sampling
influenced the structure of the bacterial community in the saltponds, which may
be related to the water temperature or other factors fluctuating over the months.
Moreover, canonical correspondence analysis of biological and physico-chemical
parameters indicated that especially other environmental factors such as
nitrogenous and phosphorous nutrient contents and pH structured the microbial
community. The relatively high range-weighted richness index and Shannon-Wiener
index (H') observed in this study reflect the high level of richness and
biodiversity present, though there were substantial fluctuations over the months
and salinities of sampling. The fragment of 16S rRNA gene sequence recovered from
DGGE bands indicated that the bacterial assemblage in Hangu Saltworks was
dominated by members of gamma-Proteobacteria (34% of total sequences obtained),
followed by Firmicutes (14%) and Bacteroidetes (9%).
PMID- 26424142
TI - Erratum to: Switching of mesodermal and endodermal properties in hTERT-modified
and expanded fetal human pancreatic progenitor cells.
PMID- 26424141
TI - Vitamin D and Clinical Outcomes in Dialysis.
AB - Most dialysis patients are vitamin D deficient, including deficiencies in both
activated vitamin D (1, 25-dihydroxyvitamin D) and the less active 25
hydroxyvitamin D. These and other abnormalities associated with chronic kidney
disease (CKD), if they remain untreated, lead to secondary hyperparathyroidism
and bone changes, such as osteitis fibrosa cystica. Activated vitamin D has been
proven to decrease parathyroid hormone (PTH) levels in dialysis patients and is
currently used for this indication. There are multiple other potential
"pleotrophic" effects associated with vitamin D therapy. These include
associations with lower all-cause and cardiovascular mortality, lower rates of
infections and improved glycemic indexes. Meta-analyses of multiple observational
studies have shown activated vitamin D therapy to be associated with improved
survival. Observational data also suggest fewer infections and better glucose
control. There have been no randomized clinical trials powered to evaluate
mortality or other clinical outcomes. Small trials of nutritional vitamin D
(ergocalciferol and cholecalciferol) showed increases in 25-hydroxyvitamin D
levels without hypercalcemia or hyperphosphatemia, even when given in addition to
activated vitamin D therapy. While activated vitamin D therapy is associated with
improved outcomes, it also leads to higher fibroblast growth factor 23 (FGF-23)
levels, which may be detrimental in dialysis patients. Further research is needed
to evaluate whether activated or nutritional vitamin D therapy are beneficial in
dialysis patients for outcomes other than secondary hyperparathyroidism.
PMID- 26424143
TI - Small bowel tuberculosis causing massive obscure gastrointestinal bleeding in an
immunocompromised patient.
PMID- 26424144
TI - Intragenic KANSL1 mutations and chromosome 17q21.31 deletions: broadening the
clinical spectrum and genotype-phenotype correlations in a large cohort of
patients.
AB - BACKGROUND: The 17q21.31 deletion syndrome phenotype can be caused by either
chromosome deletions or point mutations in the KANSL1 gene. To date, about 60
subjects with chromosome deletion and 4 subjects with point mutation in KANSL1
have been reported. Prevalence of chromosome deletions compared with point
mutations, genotype-phenotype correlations and phenotypic variability have yet to
be fully clarified. METHODS: We report genotype-phenotype correlations in 27
novel subjects with 17q21.31 deletion and in 5 subjects with KANSL1 point
mutation, 3 of whom were not previously reported. RESULTS: The prevalence of
chromosome deletion and KANSL1 mutation was 83% and 17%, respectively. All
patients had similar clinical features, with the exception of macrocephaly, which
was detected in 24% of patients with the deletion and 60% of those with the point
mutation, and congenital heart disease, which was limited to 35% of patients with
the deletion. A remarkable phenotypic variability was observed in both
categories, mainly with respect to the severity of ID. Cognitive function was
within normal parameters in one patient in each group. Craniosynostosis,
subependymal heterotopia and optic nerve hypoplasia represent new component
manifestations. CONCLUSIONS: In KANSL1 haploinsufficiency syndrome, chromosome
deletions are greatly prevalent compared with KANSL1 mutations. The latter are
sufficient in causing the full clinical phenotype. The degree of intellectual
disability (ID) appears to be milder than expected in a considerable number of
subjects with either chromosome deletion or KANSL1 mutation. Striking clinical
criteria for enrolling patients into KANSL1 analysis include speech delay,
distinctive facial dysmorphism, macrocephaly and friendly behaviour.
PMID- 26424145
TI - HACE1 deficiency causes an autosomal recessive neurodevelopmental syndrome.
AB - BACKGROUND: The genetic aetiology of neurodevelopmental defects is extremely
diverse, and the lack of distinctive phenotypic features means that genetic
criteria are often required for accurate diagnostic classification. We aimed to
identify the causative genetic lesions in two families in which eight affected
individuals displayed variable learning disability, spasticity and abnormal gait.
METHODS: Autosomal recessive inheritance was suggested by consanguinity in one
family and by sibling recurrences with normal parents in the second. Autozygosity
mapping and exome sequencing, respectively, were used to identify the causative
gene. RESULTS: In both families, biallelic loss-of-function mutations in HACE1
were identified. HACE1 is an E3 ubiquitin ligase that regulates the activity of
cellular GTPases, including Rac1 and members of the Rab family. In the
consanguineous family, a homozygous mutation p.R219* predicted a truncated
protein entirely lacking its catalytic domain. In the other family, compound
heterozygosity for nonsense mutation p.R748* and a 20-nt insertion interrupting
the catalytic homologous to the E6-AP carboxyl terminus (HECT) domain was
present; western blot analysis of patient cells revealed an absence of detectable
HACE1 protein. CONCLUSION: HACE1 mutations underlie a new autosomal recessive
neurodevelopmental disorder. Previous studies have implicated HACE1 as a tumour
suppressor gene; however, since cancer predisposition was not observed either in
homozygous or heterozygous mutation carriers, this concept may require re
evaluation.
PMID- 26424147
TI - Biogeographic distribution and metric dental variation of fossil and living
orangutans (Pongo spp.).
AB - The genus Pongo has a relatively richer Quaternary fossil record than those of
the African great apes. Fossil materials are patchy in terms of anatomical parts
represented, limited almost exclusively to isolated teeth, jaw and bone
fragments. Fossil evidence indicates that the genus Pongo had a broadly
continuous distribution across the southern part of the Indomalayan biogeographic
region, ranging in time from Early Pleistocene to Holocene: southern China (77
fossil sites), Vietnam (15), Laos (6), Cambodia (2), Thailand (4), Peninsular
Malaysia (6), Sumatra (4), Borneo (6) and Java (4). Within this distribution
range, there are major geographical gaps with no known orangutan fossils, notably
central and southern Indochina, central and southern Thailand, eastern Peninsular
Malaysia, northern and southern Sumatra, and Kalimantan. The geological time and
place of origin of the genus remain unresolved. Fossil orangutan assemblages
usually show greater extent of dental metrical variation than those of modern-day
populations. Such variability shown in prehistoric populations has partially
contributed to confusion regarding past taxonomic diversity and systematic
relationships among extinct and living forms. To date, no fewer than 14 distinct
taxa have been identified and named for Pleistocene orangutans. Clear cases
suggestive of predation by prehistoric human are few in number, and limited to
terminal Pleistocene-Early Holocene sites in Borneo and a Late Pleistocene site
in Vietnam.
PMID- 26424146
TI - Aberrant activation of NF-kappaB signaling in mammary epithelium leads to
abnormal growth and ductal carcinoma in situ.
AB - BACKGROUND: Approximately 1 in 5 women diagnosed with breast cancer are
considered to have in situ disease, most often termed ductal carcinoma in situ
(DCIS). Though recognized as a risk factor for the development of more invasive
cancer, it remains unclear what factors contribute to DCIS development. It has
been shown that inflammation contributes to the progression of a variety of tumor
types, and nuclear factor kappa B (NF-kappaB) is recognized as a master-regulator
of inflammatory signaling. However, the contributions of NF-kappaB signaling to
tumor initiation are less well understood. Aberrant up-regulation of NF-kappaB
activity, either systemically or locally within the breast, could occur due to a
variety of commonly experienced stimuli such as acute infection, obesity, or
psychological stress. In this study, we seek to determine if activation of NF
kappaB in mammary epithelium could play a role in the formation of hyperplastic
ductal lesions. METHODS: Our studies utilize a doxycycline-inducible transgenic
mouse model in which constitutively active IKKbeta is expressed specifically in
mammary epithelium. All previously published models of NF-kappaB modulation in
the virgin mammary gland have been constitutive models, with transgene or knock
out present throughout the life and development of the animal. For the first
time, we will induce activation at later time points after normal ducts have
formed, thus being able to determine if NF-kappaB activation can promote pre
malignant changes in previously normal mammary epithelium. RESULTS: We found that
even a short pulse of NF-kappaB activation could induce profound remodeling of
mammary ductal structures. Short-term activation created hyperproliferative,
enlarged ducts with filled lumens. Increased expression of inflammatory markers
was concurrent with the down-regulation of hormone receptors and markers of
epithelial differentiation. Furthermore, the oncoprotein mucin 1, known to be up
regulated in human and mouse DCIS, was over-expressed and mislocalized in the
activated ductal tissue. CONCLUSIONS: These results indicate that aberrant NF
kappaB activation within mammary epithelium can lead to molecular and
morphological changes consistent with the earliest stages of breast cancer. Thus,
inhibition of NF-kappaB signaling following acute inflammation or the initial
signs of hyperplastic ductal growth could represent an important opportunity for
breast cancer prevention.
PMID- 26424148
TI - Inhibitory effect of novel iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2
methylpyridin-4-one (CM1) and green tea extract on growth of Plasmodium
falciparum.
AB - BACKGROUND: Iron is an essential micronutrient required by all living organisms
including malaria parasites (Plasmodium spp.) for many biochemical reactions,
especially growth and multiplication processes. Therefore, malaria parasite needs
to take up the iron from outside or/and inside the parasitized red blood cells
(PRBC). Iron chelators are widely used for the treatment of thalassaemia-related
iron overload and also inhibit parasite growth at levels that are non-toxic to
mammalian cells. METHODS: Inhibitory effect of 1-(N-acetyl-6-aminohexyl)-3
hydroxy-2-methylpyridin-4-one (CM1) and green tea extract (GTE) on the growth of
malaria parasite Plasmodium falciparum was compared with standard chelators
including desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX). A flow
cytometric technique was used to enumerate PRBC stained with SYBR Green I
fluorescent dye. The labile iron pool (LIP) was assayed using the calcein
acetoxymethyl fluorescent method. RESULTS: The IC50 values of DFO, GTE, CM1, DFX
and DFP against P. falciparum were 14.09, 21.11, 35.14, 44.71 and 58.25 uM,
respectively. Importantly, CM1 was more effective in reducing LIP levels in the
P. falciparum culture than DFP (p < 0.05). CONCLUSIONS: CM1 and GTE exhibit anti
malarial activity. They could interfere with uptake of exogenous iron or deplete
the intracellular labile iron pool in malaria parasites, leading to inhibition of
their growth.
PMID- 26424149
TI - Type 5 adenylyl cyclase disruption leads to enhanced exercise performance.
AB - The most important physiological mechanism mediating enhanced exercise
performance is increased sympathetic, beta adrenergic receptor (beta-AR), and
adenylyl cyclase (AC) activity. This is the first report of decreased AC activity
mediating increased exercise performance. We demonstrated that AC5 disruption,
that is, knock out (KO) mice, a longevity model, increases exercise performance.
Importantly for its relation to longevity, exercise was also improved in old AC5
KO. The mechanism resided in skeletal muscle rather than in the heart, as
confirmed by cardiac- and skeletal muscle-specific AC5 KO's, where exercise
performance was no longer improved by the cardiac-specific AC5 KO, but was by the
skeletal muscle-specific AC5 KO, and there was no difference in cardiac output
during exercise in AC5 KO vs. WT. Mitochondrial biogenesis was a major mechanism
mediating the enhanced exercise. SIRT1, FoxO3a, MEK, and the anti-oxidant, MnSOD
were upregulated in AC5 KO mice. The improved exercise in the AC5 KO was blocked
with either a SIRT1 inhibitor, MEK inhibitor, or by mating the AC5 KO with MnSOD
hetero KO mice, confirming the role of SIRT1, MEK, and oxidative stress
mechanisms. The Caenorhabditis elegans worm AC5 ortholog, acy-3 by RNAi, also
improved fitness, mitochondrial function, antioxidant defense, and lifespan,
attesting to the evolutionary conservation of this pathway. Thus, decreasing
sympathetic signaling through loss of AC5 is not only a mechanism to improve
exercise performance, but is also a mechanism to improve healthful aging, as
exercise also protects against diabetes, obesity, and cardiovascular disease,
which all limit healthful aging.
PMID- 26424150
TI - Nonintubated Transareolar Endoscopic Thoracic Sympathectomy with a Flexible
Endoscope: Experience of 58 Cases.
AB - OBJECTIVE: Natural orifice transluminal endoscopic surgery (NOTES) has recently
become a hot spot in the field of minimally invasive surgery. But, most of the
procedures are still in the early stages of development and limited to animal
experiments. Transareolar endoscopic surgery could work as a viable intermediate
step before thoracic NOTES. Under intravenous anesthesia without endotracheal
intubation, transareolar endoscopic thoracic sympathectomy (ETS) with a flexible
endoscope has rarely been attempted. The objective of this study is to evaluate
the feasibility and safety of this novel minimally invasive technique in managing
primary palmar hyperhidrosis (PPH). METHODS: From June 2012 to July 2014, a total
of 58 male patients with severe PPH underwent transareolar ETS by use of a
flexible endoscope. Under intravenous anesthesia without endotracheal intubation,
a flexible endoscope was introduced through the incision on the edge of the
areola into the thoracic cavity. The thoracic sympathetic chain was ablated at
the level of the fourth rib. RESULTS: All procedures were successfully performed
with a mean operating time of 33.6 +/- 8.3 min. All patients regained
consciousness rapidly and none of them complained about sore throat after
surgery. There were no operative mortality and conversion to open procedure. The
symptoms of all patients disappeared as soon as the sympathetic chain was cut
off. Fifty six patients (96.6%) were discharged from the hospital on the first
postoperative day. The postoperative complications were minor, and no patients
developed Horner's syndrome. At 3 months postoperatively, there was no obvious
surgical scar on the chest wall, and none of the patients complained about
postoperative pain. Compensatory hyperhidrosis (CH) appeared in 19 patients. No
recurrent symptoms were observed in our study. One year follow-up revealed an
excellent cosmetic result and degree of satisfaction. CONCLUSION: Nonintubated
transareolar ETS with a flexible endoscope is a safe, effective and minimally
invasive therapeutic procedure, which has the possible advantages of thoracic
NOTES and can be performed in routine clinical practice for male PPH patients.
PMID- 26424151
TI - Climbing fibers mediate vestibular modulation of both "complex" and "simple
spikes" in Purkinje cells.
AB - Climbing and mossy fibers comprise two distinct afferent paths to the cerebellum.
Climbing fibers directly evoke a large multispiked action potential in Purkinje
cells termed a "complex spike" (CS). By logical exclusion, the other class of
Purkinje cell action potential, termed "simple spike" (SS), has often been
attributed to activity conveyed by mossy fibers and relayed to Purkinje cells
through granule cells. Here, we investigate the relative importance of climbing
and mossy fiber pathways in modulating neuronal activity by recording
extracellularly from Purkinje cells, as well as from mossy fiber terminals and
interneurons in folia 8-10. Sinusoidal roll-tilt vestibular stimulation
vigorously modulates the discharge of climbing and mossy fiber afferents,
Purkinje cells, and interneurons in folia 9-10 in anesthetized mice. Roll-tilt
onto the side ipsilateral to the recording site increases the discharge of both
climbing fibers (CSs) and mossy fibers. However, the discharges of SSs decrease
during ipsilateral roll-tilt. Unilateral microlesions of the beta nucleus (beta
nucleus) of the inferior olive blocks vestibular modulation of both CSs and SSs
in contralateral Purkinje cells. The blockage of SSs occurs even though primary
and secondary vestibular mossy fibers remain intact. When mossy fiber afferents
are damaged by a unilateral labyrinthectomy (UL), vestibular modulation of SSs in
Purkinje cells ipsilateral to the UL remains intact. Two inhibitory interneurons,
Golgi and stellate cells, could potentially contribute to climbing fiber-induced
modulation of SSs. However, during sinusoidal roll-tilt, only stellate cells
discharge appropriately out of phase with the discharge of SSs. Golgi cells
discharge in phase with SSs. When the vestibularly modulated discharge is blocked
by a microlesion of the inferior olive, the modulated discharge of CSs and SSs is
also blocked. When the vestibular mossy fiber pathway is destroyed, vestibular
modulation of ipsilateral CSs and SSs persists. We conclude that climbing fibers
are primarily responsible for the vestibularly modulated discharge of both CSs
and SSs. Modulation of the discharge of SSs is likely caused by climbing fiber
evoked stellate cell inhibition.
PMID- 26424152
TI - Plastic changes in spinal synaptic transmission following botulinum toxin A in
patients with post-stroke spasticity.
AB - OBJECTIVE: The therapeutic effects of intramuscular injections of botulinum toxin
type A on spasticity can largely be explained by its blocking action at the
neuromuscular junction. Botulinum toxin-type A is also thought to have a central
action on the functional organization of the central nervous system. This study
assessed the action of botulinum toxin-type A on spinal motor networks by
investigating post-activation depression of the soleus H-reflex in post-stroke
patients. Post-activation depression, a presynaptic mechanism controlling the
synaptic efficacy of Ia-motoneuron transmission, is involved in the
pathophysiology of spasticity. PATIENTS: Eight patients with chronic hemiplegia
post-stroke presenting with lower limb spasticity and requiring botulinum toxin
type A injection in the ankle extensor muscle. METHODS: Post-activation
depression of soleus H-reflex assessed as frequency-related depression of H
reflex was investigated before and 3, 6 and 12 weeks after botulinum toxin-type A
injections in the triceps surae. Post-activation depression was quantified as the
ratio between H-reflex amplitude at 0.5 and 0.1 Hz. RESULTS: Post-activation
depression of soleus H-reflex, which is reduced on the paretic leg, was affected
3 weeks after botulinum toxin-type A injection. Depending on the residual motor
capacity of the post-stroke patients, post-activation depression was either
restored in patients with preserved voluntary motor control or further reduced in
patients with no residual voluntary control. CONCLUSION: Botulinum toxin
treatment induces synaptic plasticity at the Ia-motoneuron synapse in post-stroke
paretic patients, which suggests that the effectiveness of botulinum toxin-type A
in post-stroke rehabilitation might be partly due to its central effects.
PMID- 26424153
TI - Transcriptome sequencing and analysis of major genes involved in calcium
signaling pathways in pear plants (Pyrus calleryana Decne.).
AB - BACKGROUND: Pears (Pyrus spp. L.) are an important genus of trees that produce
one of the world's oldest fruit crops. Salinity stress is a common limiting
factor for plant productivity that significantly affects the flavor and
nutritional quality of pear fruits. Much research has shown that calcium
signaling pathways, mediated by Calcineurin B-like proteins (CBLs) and their
interacting kinases (CIPKs), are closely associated with responses to stresses,
including salt. However, little is known about the molecular mechanisms that
govern the relationship between salt stress and calcium signaling pathways in
pear plants. The available genomic information for pears has promoted much
functional genomic analysis and molecular breeding of the genus. This provided an
ample foundation for characterizing the transcriptome of pear under salt stress.
RESULTS: A high-throughput Illumina RNA-seq technology was used to identify a
total of 78,695 unigenes that were successfully annotated by BLASTX analysis,
using the publicly available protein database. Additionally, 2,855 novel
transcripts, 218,167 SNPs, 23,248 indels and 18,322 alternative splicing events
occurred. Assembled unique sequences were annotated and classified with Gene
Ontology (GO), Clusters of Orthologous Group (COG) and Kyoto Encyclopedia of
Genes and Genomes (KEGG) analysis, which revealed that the main activated genes
in pear are predominately involved in functions such as basic physiological
processes, metabolic pathways, operation of cellular components, signal
transduction mechanisms, and other molecular activities. Through targeted
searches of the annotations, the majority of the genes involved in calcium
signaling pathways were identified, among which, four genes were validated by
molecular cloning, while 11 were validated by RT-qPCR expression profiles under
salt stress treatment. CONCLUSIONS: These results facilitate a better
understanding of the molecular genetics and functional genomic mechanisms of salt
stress in pear plants. Furthermore, they provide a valuable foundation for
additional research on the molecular biology and functional genomics of pear and
related species.
PMID- 26424154
TI - Suspension Array of Ionic Liquid or Ionic Liquid-Quantum Dots Conjugates for the
Discrimination of Proteins and Bacteria.
AB - It is of great importance to develop novel and sensitive sensing materials for
the detection of proteins and microorganisms to fulfill the demand of disease
diagnosis. As the selectivity and sensitivity of sensing systems are highly
dependent on the receptor, the fluorescent sensor array with imidazolium ionic
liquids (ILs) and ionic liquid-quantum dots conjugates as semiselective receptors
is developed for protein/bacteria differential sensing or discrimination. The IL
sensing system formed by 1,3-dibutylimidazolium chloride (BBimCl), 1,3
diethylimidazolium bromine (EEimBr), 1,3-dibutylimidazolium bromine (BBimBr), 1,3
dihexylimidazolium bromine (HHimBr), and 1,3-dioctylimidazolium bromine (OOimBr)
and the IL@QDs/QDs sensing system formed by CdTe, BBimCl@CdTe, EEimBr@CdTe,
BBimBr@CdTe, and HHimBr@CdTe are tested, by transferring the interaction binding
difference between receptors and proteins to the fluorescent response pattern.
The IL sensing system is applied to the identification of 48 samples (8 proteins
at 500 nM) with an accuracy of 91.7%. For the IL@QDs/QDs sensing system, 8
proteins are completely distinguished with 100% accuracy at a very low
concentration level of 10 nM. Remarkably, 36 training cases (6 strains of
bacteria from 3 different species) are discriminated with 100% (OD600 of 0.1).
PMID- 26424155
TI - Sleep and agitation in nursing home residents with and without dementia.
AB - BACKGROUND: The prevalence of dementia in Australian nursing homes is high. A
large proportion of residents express themselves through agitated behaviors, with
substantial interpersonal and day-to-day variance. One factor that may increase
agitation is poor sleep. The current study aimed to determine if sleep influences
symptoms of agitation in nursing home residents, and whether this effect differed
by dementia status. As benzodiazepines are used widely as hypnotic medication,
their impact was also considered. METHODS: Actigraph devices worn on residents'
non-dominant wrists for three days were used to obtain objective measures of
sleep. Symptoms of agitation were assessed using staff responses to two
standardized questionnaires - the Cohen-Mansfield Agitation Inventory (CMAI) and
the Neuropsychiatric Inventory - nursing home version (NPI-NH). Presence of
dementia and benzodiazepine use were obtained from resident medical charts.
RESULTS: Forty-nine residents (mean age: 85.57 years) from four nursing homes in
Tasmania were included in the study. Results indicated that residents were in bed
for an average of 11.04 h and slept for 10.14 h per day. Significant
relationships between sleep and verbal as well as non-aggressive agitation were
found. No relationships between sleep and aggressive agitation were detected. A
significant moderation effect of dementia was found, in which residents without
dementia expressed verbal agitation when obtaining less sleep, but not residents
with dementia. Benzodiazepine use did not result in significantly more sleep.
CONCLUSIONS: These results suggest that sleep could play an important role in
explaining agitation, but more research is needed to explore the relationship
between sleep and benzodiazepines in nursing home residents.
PMID- 26424156
TI - GP is struck off for dishonestly providing sick notes for children.
PMID- 26424157
TI - Rice SPX-Major Facility Superfamily3, a Vacuolar Phosphate Efflux Transporter, Is
Involved in Maintaining Phosphate Homeostasis in Rice.
AB - To maintain a stable cytosol phosphate (Pi) concentration, plant cells store Pi
in their vacuoles. When the Pi concentration in the cytosol decreases, Pi is
exported from the vacuole into the cytosol. This export is mediated by Pi
transporters on the tonoplast. In this study, we demonstrate that SYG1, PHO81,
and XPR1 (SPX)-Major Facility Superfamily (MFS) proteins have a similar structure
with yeast (Saccharomyces cerevisiae) low-affinity Pi transporters Phosphatase87
(PHO87), PHO90, and PHO91. OsSPX-MFS1, OsSPX-MFS2, and OsSPX-MFS3 all localized
on the tonoplast of rice (Oryza sativa) protoplasts, even in the absence of the
SPX domain. At high external Pi concentration, OsSPX-MFS3 could partially
complement the yeast mutant strain EY917 under pH 5.5, which lacks all five Pi
transporters present in yeast. In oocytes, OsSPX-MFS3 was shown to facilitate Pi
influx or efflux depending on the external pH and Pi concentrations. In contrast
to tonoplast localization in plants cells, OsSPX-MFS3 was localized to the plasma
membrane when expressed in both yeast and oocytes. Overexpression of OsSPX-MFS3
results in decreased Pi concentration in the vacuole of rice tissues. We conclude
that OsSPX-MFS3 is a low-affinity Pi transporter that mediates Pi efflux from the
vacuole into cytosol and is coupled to proton movement.
PMID- 26424160
TI - Constructing a representative sample of out-of-care HIV patients from a
representative sample of in-care patients.
AB - Individuals infected with HIV who are out of care are at a higher risk of HIV
related morbidity and mortality. It has been difficult to recruit a
representative sample of out-of-care patients for epidemiological studies. Using
a novel weighting method, we constructed a representative sample of out-of-care
HIV patients from a representative sample of in-care patients. In-care patients
were weighted based on the probability of receiving care during the study period
and the probability of selection to participate in the study, and out-of-care
patients were represented by those who were previously out of care and recently
returned. The method can be used in other patient populations, if every patient
in the population has a known, non-zero probability of receiving care and a
known, non-zero probability of participating in the study.
PMID- 26424158
TI - OsMADS26 Negatively Regulates Resistance to Pathogens and Drought Tolerance in
Rice.
AB - Functional analyses of MADS-box transcription factors in plants have unraveled
their role in major developmental programs (e.g. flowering and floral organ
identity) as well as stress-related developmental processes, such as abscission,
fruit ripening, and senescence. Overexpression of the rice (Oryza sativa) MADS26
gene in rice has revealed a possible function related to stress response. Here,
we show that OsMADS26-down-regulated plants exhibit enhanced resistance against
two major rice pathogens: Magnaporthe oryzae and Xanthomonas oryzae. Despite this
enhanced resistance to biotic stresses, OsMADS26-down-regulated plants also
displayed enhanced tolerance to water deficit. These phenotypes were observed in
both controlled and field conditions. Interestingly, alteration of OsMADS26
expression does not have a strong impact on plant development. Gene expression
profiling revealed that a majority of genes misregulated in overexpresser and
down-regulated OsMADS26 lines compared with control plants are associated to
biotic or abiotic stress response. Altogether, our data indicate that OsMADS26
acts as an upstream regulator of stress-associated genes and thereby, a hub to
modulate the response to various stresses in the rice plant.
PMID- 26424161
TI - Correlates of HIV infection among street-based and venue-based sex workers in
Vietnam.
AB - Commercial sex work is one of the driving forces of the HIV epidemic across the
world. In Vietnam, although female sex workers (FSWs) carry a disproportionate
burden of HIV, little is known about the risk profile and associated factors for
HIV infection among this population. There is a need for large-scale research to
obtain reliable and representative estimates of the measures of association. This
study involved secondary data analysis of the 'HIV/STI Integrated Biological and
Behavioral Surveillance' study in Vietnam in 2009-2010 to examine the correlates
of HIV among FSWs. Data collected from 5298 FSWs, including 2530 street-based sex
workers and 2768 venue-based sex workers from 10 provinces in Vietnam, were
analyzed using descriptive statistics and bivariate and multivariate logistic
regression analyses. HIV prevalence among the overall FSW population was 8.6% (n
= 453). However, when stratified by FSW subpopulations, HIV prevalence was 10.6%
(n = 267) for street-based sex workers and 6.7% (n = 186) for venue-based sex
workers. Factors independently associated with HIV infection in the multivariate
analysis, regardless of sex work types, were injecting drug use, high self
perceived HIV risk, and age >= 25 years. Additional factors independently
associated with HIV risk within each FSW subpopulation included having ever been
married among street-based sex workers and inconsistent condom use with clients
and having sex partners who injected drugs among venue-based sex workers. Apart
from strategies addressing modifiable risk behaviours among all FSWs, targeted
strategies to address specific risk behaviours within each FSW subpopulation
should be adopted.
PMID- 26424159
TI - Metabolite Profiles of Maize Leaves in Drought, Heat, and Combined Stress Field
Trials Reveal the Relationship between Metabolism and Grain Yield.
AB - The development of abiotic stress-resistant cultivars is of premium importance
for the agriculture of developing countries. Further progress in maize (Zea mays)
performance under stresses is expected by combining marker-assisted breeding with
metabolite markers. In order to dissect metabolic responses and to identify
promising metabolite marker candidates, metabolite profiles of maize leaves were
analyzed and compared with grain yield in field trials. Plants were grown under
well-watered conditions (control) or exposed to drought, heat, and both stresses
simultaneously. Trials were conducted in 2010 and 2011 using 10 tropical hybrids
selected to exhibit diverse abiotic stress tolerance. Drought stress evoked the
accumulation of many amino acids, including isoleucine, valine, threonine, and 4
aminobutanoate, which has been commonly reported in both field and greenhouse
experiments in many plant species. Two photorespiratory amino acids, glycine and
serine, and myoinositol also accumulated under drought. The combination of
drought and heat evoked relatively few specific responses, and most of the
metabolic changes were predictable from the sum of the responses to individual
stresses. Statistical analysis revealed significant correlation between levels of
glycine and myoinositol and grain yield under drought. Levels of myoinositol in
control conditions were also related to grain yield under drought. Furthermore,
multiple linear regression models very well explained the variation of grain
yield via the combination of several metabolites. These results indicate the
importance of photorespiration and raffinose family oligosaccharide metabolism in
grain yield under drought and suggest single or multiple metabolites as potential
metabolic markers for the breeding of abiotic stress-tolerant maize.
PMID- 26424163
TI - Junior doctors' dispute is result of financial mismanagement, Labour says.
PMID- 26424162
TI - Design, synthesis and antiviral evaluation of 2'-C-methyl branched guanosine
pronucleotides: the discovery of IDX184, a potent liver-targeted HCV polymerase
inhibitor.
AB - BACKGROUND: Ribonucleoside analogs possessing a beta-methyl substituent at the 2'
position of the d-ribose moiety have been previously discovered to be potent and
selective inhibitors of hepatitis C virus (HCV) replication, their triphosphates
acting as alternative substrate inhibitors of the HCV RdRp NS5B.
Results/methodology: In this article, the authors detail the synthesis, anti-HCV
evaluation in cell-based replicon assays and structure-activity relationships of
several phosphoramidate diester derivatives of 2'-C-methylguanosine (2'-MeG).
CONCLUSION: The most promising compound, namely the O-[S-(hydroxyl)pivaloyl-2
thioethyl]{abbreviated as O-[(HO)tBuSATE)]} N-benzylamine phosphoramidate diester
derivative (IDX184), was selected for further in vivo studies, and was the first
clinical pronucleotide evaluated for the treatment of chronic hepatitis C up to
Phase II trials.
PMID- 26424164
TI - The Stomach-Derived Hormone Ghrelin Increases Impulsive Behavior.
AB - Impulsivity, defined as impaired decision making, is associated with many
psychiatric and behavioral disorders, such as attention-deficit/hyperactivity
disorder as well as eating disorders. Recent data indicate that there is a strong
positive correlation between food reward behavior and impulsivity, but the
mechanisms behind this relationship remain unknown. Here we hypothesize that
ghrelin, an orexigenic hormone produced by the stomach and known to increase food
reward behavior, also increases impulsivity. In order to assess the impact of
ghrelin on impulsivity, rats were trained in three complementary tests of
impulsive behavior and choice: differential reinforcement of low rate (DRL),
go/no-go, and delay discounting. Ghrelin injection into the lateral ventricle
increased impulsive behavior, as indicated by reduced efficiency of performance
in the DRL test, and increased lever pressing during the no-go periods of the
go/no-go test. Central ghrelin stimulation also increased impulsive choice, as
evidenced by the reduced choice for large rewards when delivered with a delay in
the delay discounting test. In order to determine whether signaling at the
central ghrelin receptors is necessary for maintenance of normal levels of
impulsive behavior, DRL performance was assessed following ghrelin receptor
blockade with central infusion of a ghrelin receptor antagonist. Central ghrelin
receptor blockade reduced impulsive behavior, as reflected by increased
efficiency of performance in the DRL task. To further investigate the
neurobiological substrate underlying the impulsivity effect of ghrelin, we
microinjected ghrelin into the ventral tegmental area, an area harboring
dopaminergic cell bodies. Ghrelin receptor stimulation within the VTA was
sufficient to increase impulsive behavior. We further evaluated the impact of
ghrelin on dopamine-related gene expression and dopamine turnover in brain areas
key in impulsive behavior control. This study provides the first demonstration
that the stomach-produced hormone ghrelin increases impulsivity and also
indicates that ghrelin can change two major components of impulsivity-motor and
choice impulsivity.
PMID- 26424166
TI - Explicating perceived barriers to mammography for the USCREEN project: concerns
about breast implants, faith violations, and perceived recommendations.
AB - In line with the health belief model, perceived barriers have proven to be a key
determinant of intentions to screen for breast cancer. The standard measure of
perceived barriers to breast cancer screening is an 11 item scale developed by
Victoria Champion. However, perceived barriers emerge and change over time, and
Champion's perceived barriers scale was last revised in 1999. Moreover, the
original scale did not address barriers which may be more pronounced in
particular populations, such as congruity of action with faith. As part of the
Utah Screening Project, a sample of women 40-74 (N = 341, Mage = 51.19, SD =
8.11) were recruited from four Utah counties in 2014 to complete a survey. The
results revealed that the four new perceived barrier items explained 6.4 % of
intentions to screen, above and beyond other predictors. In addition to barriers
identified in past research, the current study identified several novel barriers
including (a) concerns about negative effects to breast implants, (b) perceived
conflict with faith, and the (c) perception that mammography is no longer
recommended. The new perceived barriers items are useful to researchers
interested in exploring barriers not addressed by the original instrument. The
barriers also suggest potential belief-based targets and channels (e.g., plastic
surgery clinics, faith-based interventions) for delivering mammography
interventions.
PMID- 26424165
TI - Metabolic and anthropometric changes in early breast cancer patients receiving
adjuvant therapy.
AB - Weight gain and metabolic changes have been related to survival of early breast
cancer patients (EBC). ''However, factors influencing metabolism post-diagnosis
are not fully understood. We measured anthropometric [body mass index (BMI), body
weight, waist and hip circumferences, and waist-to-hip ratio] and metabolic
(levels of insulin, glucose, H1Ac, total, HDL, and LDL cholesterol,
triglycerides, and the homeostasis model assessment score [HOMA]) parameters in
433 pre- and post-menopausal women with EBC at diagnosis and 3, 6, 9, 12, and 24
months thereafter. At diagnosis, compared with post-menopausal women, pre
menopausal patients were more likely to be leaner and to have a lower BMI,
smaller waist and hip circumferences, and waist-to-hip ratio. They had also lower
glucose, HbA1c, and triglyceride levels and a lower HOMA score. Furthermore, they
were more likely to have an estrogen- and/or progesterone-positive tumor and a
higher proliferating breast cancer. During the first two post-diagnosis years,
all women showed a significant increase of weight (+0.72 kg/year, P < 0.001),
waist circumference (+1.53 cm/year, P < 0.001), and plasma levels of LDL
cholesterol (+5.4 mg/dl per year, P = 0.045) and triglycerides (+10.73 mg/dl per
year, P = 0.017). In patients receiving chemotherapy only, there was a
significant increase in hip circumference (+3.16 cm/year, P < 0.001) and plasma
cholesterol levels (+21.26 mg/dl per year, P < 0.001). We showed that weight,
body fat distribution, and lipid profile changed in EBC patients receiving
adjuvant therapy. These changes occurred during the first 2 years after diagnosis
and were not specifically related to chemotherapy, menopausal status, or initial
body weight.
PMID- 26424167
TI - Molecular subtyping improves diagnostic stratification of patients with primary
breast cancer into prognostically defined risk groups.
AB - Combined use of MammaPrint and a molecular subtyping profile (BluePrint)
identifies disease subgroups with marked differences in long-term outcome and
response to neo-adjuvant therapy. The aim of this study was to evaluate the
prognostic value of molecular subtyping using MammaPrint and BluePrint in women
with early-stage breast cancer (BC) treated at US institutions following National
Comprehensive Cancer Network standard guidelines. Tumor samples were collected
from stage 1-2B consecutively diagnosed BC patients (n = 373) who underwent
lumpectomy or mastectomy with an axillary staging procedure between 1992 and 2010
at two institutes (NorthShore University HealthSystem and Fox Chase Cancer
Center) in the United States of America, with a median follow-up time of 9.5
years. MammaPrint low-risk patients had a 10-year DMFS of 96 % (95 %CI 92.8
99.4), while MammaPrint high-risk patients had a 10-year DMFS of 87 % (95 %CI
81.9-92.1) with a hazard ratio of 3.62 (95 %CI 1.38-9.50) (p = 0.005). Uni- and
multivariate analyses included age, tumor size, grade, ER, and Her2; in
multivariate analysis, MammaPrint reached near-significance (HR 3.01; p 0.08).
When comparing BluePrint molecular subtyping with clinical stratification, the
prognosis (10-year DMFS) was significantly different in 10-year DMFS between the
different molecular subtypes (p < 0.001). This retrospective study with 10-year
follow-up data provides valuable insight into prognosis of patients with primary
BC comparing clinical with molecular subtyping. The BluePrint molecular
stratification assay identifies patients with significantly different outcomes
compared with standard clinical molecular stratification.
PMID- 26424168
TI - Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the
neuroprotective effects of melatonin.
AB - Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a
substitute for other plasticizers whose use is prohibited in certain products. In
vivo studies on the neurotoxicity of DINP are however, limited. This work aims to
investigate whether DINP causes neurobehavioral changes in mice and to provide
useful advice on preventing the occurrence of these adverse effects. Behavioral
analysis showed that oral administration of 20 or 200 mg/kg/day DINP led to mouse
cognitive deficits and anxiety. Brain histopathological observations,
immunohistochemistry assays (cysteine-aspartic acid protease 3 [caspase-3], glial
fibrillary acidic protein [GFAP]), oxidative stress assessments (reactive oxygen
species [ROS], glutathione [GSH], superoxide dismutase [SOD] activities, 8
hydroxy-2-deoxyguanosine [8-OH-dG] and DNA-protein crosslinks [DPC]), and
assessment of inflammation (tumor necrosis factor alpha [TNF-a] and interleukin-1
beta [IL-1beta]) of mouse brains showed that there were histopathological
alterations in the brain and increased levels of oxidative stress, and
inflammation for these same groups. However, some of these effects were blocked
by administration of melatonin (50 mg/kg/day). Down-regulation of oxidative
stress was proposed to explain the neuroprotective effects of melatonin. The data
suggests that DINP could cause cognitive deficits and anxiety in mice, and that
melatonin could be used to avoid these adverse effects.
PMID- 26424170
TI - Treatment satisfaction in type 2 diabetes patients taking empagliflozin compared
with patients taking glimepiride.
AB - PURPOSE: This exploratory analysis assessed and compared patients' treatment
satisfaction with empagliflozin plus metformin versus glimepiride plus metformin,
using data obtained from the Diabetes Treatment Satisfaction Questionnaire,
status version (DTSQs) collected in a randomized, double-blind, double-dummy
clinical trial. METHODS: Observed values for DTSQs scale score and each of its
eight items were summarized by visit and treatment arm. Changes from baseline in
these scores were analyzed using linear mixed models for repeated measures.
RESULTS: The baseline scale score and item scores were comparable between
empagliflozin plus metformin (n = 765) and glimepiride plus metformin (n = 780).
Compared with baseline, patients reported significant treatment satisfaction
increases and significant decreases in perceived hyperglycemia with both
treatments at all visits. Also, compared with baseline, a significant increase in
perceived frequency of hypoglycemia was observed in the glimepiride treatment
group at all visits. No statistically significant treatment difference was
observed in DTSQs scale score and its items at week 104. The difference between
the treatment groups was significant and in favor of empagliflozin from week 28
onward for perceived frequency of hyperglycemia (P <= 0.006) and perceived
frequency of hypoglycemia (P <= 0.011). CONCLUSIONS: Despite positive trends in
favor of empagliflozin, there was no significant difference in DTSQs scale score
between empagliflozin and glimepiride at 104 weeks. However, when compared with
glimepiride, empagliflozin demonstrated significantly lower perceived frequency
of hyperglycemia and hypoglycemia at all visits from week 28 onward. This finding
is consistent with the clinical results reported for the EMPA-REG H2H-SU trial.
PMID- 26424169
TI - Linkage between the PROMIS(r) pediatric and adult emotional distress measures.
AB - PURPOSE: Research studies that measure health-related quality of life (HRQOL) in
both children and adults and longitudinal studies that follow children into
adulthood need measures that can be compared across these age groups. This study
links the PROMIS pediatric and adult emotional distress measures using data from
participants with diverse health conditions and disabilities. METHODS: Analyses
were conducted and compared in two separate samples to confirm the stability of
results. One sample (n = 874) included individuals aged 14-20 years with special
health care needs and who require health services. The other sample (n = 641)
included individuals aged 14-25 years who have a physical or cognitive
disability. Participants completed both PROMIS pediatric and adult measures. Item
response theory-based scores were linked using the linear approximation to
calibrated projection. RESULTS: The estimated latent-variable correlation between
pediatric and adult PROMIS measures ranged from 0.87 to 0.94. Regression
coefficients beta 0 (intercept) and beta 1 (slope), and mean squared error are
provided to transform scores from the pediatric to the adult measures, and vice
versa. CONCLUSIONS: This study used a relatively new linking method, calibrated
projection, to link PROMIS pediatric and adult measure scores, thus expanding the
use of PROMIS measures to research that includes both populations.
PMID- 26424171
TI - Enhancing cancer clonality analysis with integrative genomics.
AB - INTRODUCTION: It is understood that cancer is a clonal disease initiated by a
single cell, and that metastasis, which is the spread of cancer from the primary
site, is also initiated by a single cell. The seemingly natural capability of
cancer to adapt dynamically in a Darwinian manner is a primary reason for
therapeutic failures. Survival advantages may be induced by cancer therapies and
also occur as a result of inherent cell and microenvironmental factors. The
selected "more fit" clones outmatch their competition and then become dominant in
the tumor via propagation of progeny. This clonal expansion leads to relapse,
therapeutic resistance and eventually death. The goal of this study is to develop
and demonstrate a more detailed clonality approach by utilizing integrative
genomics. METHODS: Patient tumor samples were profiled by Whole Exome Sequencing
(WES) and RNA-seq on an Illumina HiSeq 2500 and methylation profiling was
performed on the Illumina Infinium 450K array. STAR and the Haplotype Caller were
used for RNA-seq processing. Custom approaches were used for the integration of
the multi-omic datasets. RESULTS: Reported are major enhancements to CloneViz,
which now provides capabilities enabling a formal tumor multi-dimensional
clonality analysis by integrating: i) DNA mutations, ii) RNA expressed mutations,
and iii) DNA methylation data. RNA and DNA methylation integration were not
previously possible, by CloneViz (previous version) or any other clonality method
to date. This new approach, named iCloneViz (integrated CloneViz) employs
visualization and quantitative methods, revealing an integrative genomic
mutational dissection and traceability (DNA, RNA, epigenetics) thru the different
layers of molecular structures. CONCLUSION: The iCloneViz approach can be used
for analysis of clonal evolution and mutational dynamics of multi-omic data sets.
Revealing tumor clonal complexity in an integrative and quantitative manner
facilitates improved mutational characterization, understanding, and therapeutic
assignments.
PMID- 26424172
TI - Diversifying crop rotations with pulses enhances system productivity.
AB - Agriculture in rainfed dry areas is often challenged by inadequate water and
nutrient supplies. Summerfallowing has been used to conserve rainwater and
promote the release of nitrogen via the N mineralization of soil organic matter.
However, summerfallowing leaves land without any crops planted for one entire
growing season, creating lost production opportunity. Additionally,
summerfallowing has serious environmental consequences. It is unknown whether
alternative systems can be developed to retain the beneficial features of
summerfallowing with little or no environmental impact. Here, we show that
diversifying cropping systems with pulse crops can enhance soil water
conservation, improve soil N availability, and increase system productivity. A 3
yr cropping sequence study, repeated for five cycles in Saskatchewan from 2005 to
2011, shows that both pulse- and summerfallow-based systems enhances soil N
availability, but the pulse system employs biological fixation of atmospheric N2,
whereas the summerfallow-system relies on 'mining' soil N with depleting soil
organic matter. In a 3-yr cropping cycle, the pulse system increased total grain
production by 35.5%, improved protein yield by 50.9%, and enhanced fertilizer-N
use efficiency by 33.0% over the summerfallow system. Diversifying cropping
systems with pulses can serve as an effective alternative to summerfallowing in
rainfed dry areas.
PMID- 26424173
TI - Clinical profiles of moderate and severe Crohn's disease patients and use of anti
tumor necrosis factor agents: Greek expert consensus guidelines.
AB - Crohn's disease (CD) is a chronic idiopathic inflammatory bowel disease (IBD)
which affects any site of the gastrointestinal tract and occasionally
extraintestinal organs. The natural history of CD varies remarkably but a
considerable proportion of patients develop complications leading to
hospitalizations and surgeries, impaired quality of life, and disability. In
these patients, effective medical therapy should aim beyond control of clinical
symptoms to include induction and maintenance of steroid-free clinical and
serological remission and mucosal healing, as this has shown to reduce
complications, hospitalizations and surgeries, and to decrease the risk of
colorectal cancer, at least in the short term. This therapeutic goal can be
achieved in a considerable proportion of patients with anti-tumor necrosis factor
(TNF)-alpha agents if applied early in the disease course. Clinical
recommendations from a panel of Greek IBD experts are herein provided, regarding
the clinical profiles and the use of anti-TNF-alpha therapy in patients with
moderate and severe CD, based on literature review and personal experience. The
objectives of this advisory workshop were to define the profiles of patients with
moderate and severe CD using routine clinical and laboratory parameters, as well
as the clinical profiles of patients with moderate CD, severe CD, perianal CD,
and/or extra-intestinal manifestations, who are candidates for biologic
therapies. Emphasis was given on patients with newly diagnosed CD. The proposed
recommendations may provide a useful and practical approach for improving
therapeutic strategies with anti-TNF-alpha in patients with active moderate and
severe CD.
PMID- 26424174
TI - Radioactive iodine (RAI) therapy for distantly metastatic differentiated thyroid
cancer (DTC) in juvenile versus adult patients.
AB - In general, juvenile differentiated thyroid carcinoma (DTC) demonstrate indolent
characteristics and favorable prognosis are observed in comparison with many
other carcinomas. However, recurrence is frequent, necessitating additional
treatment, including radioactive iodine (RAI) therapy. In this report, the
probability of recurrence, prognostic factors, treatment, and outcomes in both
juvenile- and adult-onset DTC were analyzed and compared. At our institution, a
total of 1552 DTC patients underwent thyroidectomy and/or lymph node dissection.
The patients included 23 in their teens, 118 in their twenties, and 1412 in their
thirties or older. The risk factors for distant metastases for DTC were male
gender, follicular carcinoma, size of the PTC primary tumor, cervical lymph node
metastases from PTC, and the presence of more than two distant metastatic foci.
Patients with the highest risk underwent RAI ablation in line with institutional
guidelines. Although the overall outcome in our juvenile patients was excellent,
during follow-up, 4 (17.4%) of the 23 patients developed recurrent disease: 91.3%
achieved complete remission, 4.35% partial remission, and 4.35% stable disease,
with no disease-related deaths. Among the 118 patients in their twenties to
thirties, 1 (0.8%) experienced progressive disease and disease-related death. A
younger age at diagnosis and less radical primary surgery without subsequent RAI
ablation are factors strongly predictive of distant metastases in patients with
juvenile-onset DTC. To reduce the rate of relapse and improve surveillance for
recurrent disease, total thyroidectomy followed by RAI appears to be the most
beneficial initial treatment for patients with high- and intermediate-risk
juvenile DTC.
PMID- 26424175
TI - Resonant Scanning with Large Field of View Reduces Photobleaching and Enhances
Fluorescence Yield in STED Microscopy.
AB - Photobleaching is a major limitation of superresolution Stimulated Depletion
Emission (STED) microscopy. Fast scanning has long been considered an effective
means to reduce photobleaching in fluorescence microscopy, but a careful
quantitative study of this issue is missing. In this paper, we show that the
photobleaching rate in STED microscopy can be slowed down and the fluorescence
yield be enhanced by scanning with high speed, enabled by using large field of
view in a custom-built resonant-scanning STED microscope. The effect of scanning
speed on photobleaching and fluorescence yield is more remarkable at higher
levels of depletion laser irradiance, and virtually disappears in conventional
confocal microscopy. With >=6 GW?cm(-2) depletion irradiance, we were able to
extend the fluorophore survival time of Atto 647N and Abberior STAR 635P by ~80%
with 8-fold wider field of view. We confirm that STED Photobleaching is primarily
caused by the depletion light acting upon the excited fluorophores. Experimental
data agree with a theoretical model. Our results encourage further increasing the
linear scanning speed for photobleaching reduction in STED microscopy.
PMID- 26424176
TI - Linezolid Induced Adverse Drug Reactions - An Update.
AB - Treatment regimen recommended for resistant tuberculosis consists of various
drugs and these drugs are prescribed for at least 12-15 months. Such a long
duration therapy and high dose of antibiotics result in adverse drug reactions
(ADRs). ADRs may lead to various complications in disease management like
replacement of drugs, dose increment, therapy withdrawal, etc. Linezolid is one
of those drugs, practiced as an anti-mycobacterial agent and it is an important
member of drug regimen for MDR and XDR tuberculosis. Linezolid is a broad
spectrum antibiotic known for its unique mechanism of inhibition of resistant
pathogenic strains. However, it causes serious adverse effects like
thrombocytopenia, optic neuropathy, peripheral neuropathy, lactic acidosis, etc.
Literature suggests that Linezolid can cause severe ADRs which affect patient
compliance and hinder in therapy to a larger extent. Recent studies confirm the
possibility of ADRs to be predicted with genetic make-up of individuals. To
effectively deliver the available treatment regimen and ensure patient
compliance, it is important to manage ADRs more efficiently. The role of
pharmacogenomics in reducing adverse drug effects has been recently explored. In
the present review, we discussed about Linezolid induced adverse drug reactions,
mechanisms and genetic associations.
PMID- 26424177
TI - Pharmacokinetic and Pharmacodynamic Properties of Anti-VEGF Drugs After
Intravitreal Injection.
AB - Subretinal neovascularization and pathologic ocular angiogenesis are common
causes of progressive, irreversible impairment of central vision, and
dramatically affect quality of life. Anti-vascular endothelial growth factor
(anti-VEGF) therapy has improved the quality of life for many patients with age
related macular degeneration, diabetic retinopathy, and other ocular diseases
involving neovascularization and edema. In these pathologies, the inhibition of
intraocular VEGF is the only therapy that can preserve vision. Four anti-VEGF
drugs are currently used to treat ocular neovascularization; pegaptanib,
ranibizumab, and aflibercept have been approved for this condition, while
bevacizumab can be used off-label. Anti-VEGF therapy is administered regularly
for many months or years because its suspension or discontinuation may cause
recurrence of neovascularization. On the other hand, VEGF is necessary for the
survival of retinal and choroidal endothelial cells. Experimental studies in
animal models have shown that local inhibition of VEGF causes thinning and
atrophy of the choriocapillaris and degeneration of photoreceptors, primarily
cones. These studies combined with clinical experience indicated that prolonged
VEGF inhibition could impair retinal function. Moreover, anti-VEGF compounds can
cross the blood-retina barrier, enter the systemic circulation, and inhibit serum
VEGF. Since circulating VEGF protects blood vessel integrity, prolonged anti-VEGF
treatment could induce thromboembolic adverse events from vascular causes such as
heart attack and stroke, and even death. The ocular dosing regimen and systemic
toxicity of anti-VEGF compounds are therefore central concerns. A better
understanding of this topic requires knowledge of the metabolism, tissue
distribution, and clearance of anti-VEGF compounds. This manuscript reviews the
properties of anti-VEGF compounds following intravitreal administration.
PMID- 26424178
TI - Comparison of sedation and general anaesthesia for transcatheter aortic valve
implantation on cerebral oxygen saturation and neurocognitive outcome?.
AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a treatment
strategy for patients with severe aortic stenosis. Although general anaesthesia
(TAVI-GA) and sedation (TAVI-S) have previously been described for TAVI, the
difference in safety and efficacy of both methods has not been studied in a
randomized trial. METHODS: The INSERT trial was a single centre, controlled
parallel-group trial with balanced randomization. Sixty-six patients (68-94 yr)
with acquired aortic stenosis undergoing transfemoral CoreValveTM were assigned
to TAVI-GA or TAVI-S. Comparable operative risk was determined from risk-scores
(EUROscore, STS-Score). Monitoring and anaesthetic drugs were standardized. Near
Infrared-Spectroscopy was used to monitor cerebral-oxymetry blinded. Primary
outcome was the perioperative cumulative cerebral desaturation. As secondary
outcomes, changes in neurocognitive function and respiratory and haemodynamic
adverse events were evaluated. RESULTS: Of 66 included patients, 62 (TAVI-GA:
n=31, TAVI-S: n=31) were finally analysed. Baseline characteristics were
comparable. In 24 patients (39%) cerebral desaturation was observed. Cumulative
cerebral desaturation was comparable (TAVI-GA:(median [IQR]) (0[0/1308] s%) vs.
TAVI-S:(0[0/276] s%); P=0.505) between the groups. Neurocognitive function did
not change within and between groups. Adverse events were more frequently
observed in TAVI-S patients (P<0.001). Bradypnoea (n=16, 52%) and the need for
airway manoeuvres (n=11, 36%) or bag-mask-ventilation (n=6, 19%) were the most
common respiratory adverse events. CONCLUSIONS: Cerebral desaturation occurred in
both patient groups, but there was no significant difference between the two
groups. Based on primary outcome, both methods were shown to be comparable.
Neurocognitive outcome was similar. The higher incidence of adverse events in the
sedation group suggests a potential advantage of general anaesthesia. CLINICAL
TRIAL REGISTRATION: NCT 01251328.
PMID- 26424179
TI - Reaching with the sixth sense: Vestibular contributions to voluntary motor
control in the human right parietal cortex.
AB - The vestibular system constitutes the silent sixth sense: It automatically
triggers a variety of vital reflexes to maintain postural and visual stability.
Beyond their role in reflexive behavior, vestibular afferents contribute to
several perceptual and cognitive functions and also support voluntary control of
movements by complementing the other senses to accomplish the movement goal.
Investigations into the neural correlates of vestibular contribution to voluntary
action in humans are challenging and have progressed far less than research on
corresponding visual and proprioceptive involvement. Here, we demonstrate for the
first time with event-related TMS that the posterior part of the right medial
intraparietal sulcus processes vestibular signals during a goal-directed reaching
task with the dominant right hand. This finding suggests a qualitative difference
between the processing of vestibular vs. visual and proprioceptive signals for
controlling voluntary movements, which are pre-dominantly processed in the left
posterior parietal cortex. Furthermore, this study reveals a neural pathway for
vestibular input that might be distinct from the processing for reflexive or
cognitive functions, and opens a window into their investigation in humans.
PMID- 26424180
TI - Topology of genetic associations between regional gray matter volume and
intellectual ability: Evidence for a high capacity network.
AB - Intelligence is associated with a network of distributed gray matter areas
including the frontal and parietal higher association cortices and primary
processing areas of the temporal and occipital lobes. Efficient information
transfer between gray matter regions implicated in intelligence is thought to be
critical for this trait to emerge. Genetic factors implicated in intelligence and
gray matter may promote a high capacity for information transfer. Whether these
genetic factors act globally or on local gray matter areas separately is not
known. Brain maps of phenotypic and genetic associations between gray matter
volume and intelligence were made using structural equation modeling of 3T MRI T1
weighted scans acquired in 167 adult twins of the newly acquired U-TWIN cohort.
Subsequently, structural connectivity analyses (DTI) were performed to test the
hypothesis that gray matter regions associated with intellectual ability form a
densely connected core. Gray matter regions associated with intellectual ability
were situated in the right prefrontal, bilateral temporal, bilateral parietal,
right occipital and subcortical regions. Regions implicated in intelligence had
high structural connectivity density compared to 10,000 reference networks
(p=0.031). The genetic association with intelligence was for 39% explained by a
genetic source unique to these regions (independent of total brain volume), this
source specifically implicated the right supramarginal gyrus. Using a twin
design, we show that intelligence is genetically represented in a spatially
distributed and densely connected network of gray matter regions providing a high
capacity infrastructure. Although genes for intelligence have overlap with those
for total brain volume, we present evidence that there are genes for intelligence
that act specifically on the subset of brain areas that form an efficient brain
network.
PMID- 26424181
TI - Extracellular polysaccharide from Bordetella species reduces high glucose-induced
macrophage apoptosis via regulating interaction between caveolin-1 and TLR4.
AB - Microphage apoptosis is a critical event in atherosclerotic lesions in patients
with diabetes. In the present investigation, high glucose treatment inhibited Akt
phosphorylation and activated caspase 3 in primary peritoneal macrophage, leading
to cell apoptosis. Hypoxia prolonged macrophage survival in high glucose
condition. Extracellular polysaccharide from Bordetella species (EPS) further
decreased cell apoptosis in response to high glucose during hypoxia. Under high
glucose and hypoxic condition, EPS treatment promoted caveolin-1 phosphorylation
by recognizing TLR4. Caveolin-1 phosphorylation elevated membrane Glut1 level to
accelerate glucose consumption, which should be the reason for protective effect
of EPS on macrophage exposed to high glucose. Further investigation demonstrated
that TLR4-dependent caveolin-1 phosphorylation induced by EPS promoted
association of caveolin-1 with TLR4, which should be critical for activation of
TLR4 signaling pathway.
PMID- 26424182
TI - Erysipelas, a large retrospective study of aetiology and clinical presentation.
AB - BACKGROUND: Erysipelas is a common and severe infection where the aetiology and
optimal management is not well-studied. Here, we investigate the clinical
features, bacteriological aetiology, and treatment of erysipelas. METHODS:
Episodes of erysipelas in a seven-years period in our institution were studied
retrospectively using a pre-specified protocol and is presented with descriptive
and comparative statistics. RESULTS: 1142 episodes of erysipelas were identified
in 981 patients. Patients had a median age of 61 years, 59 % were male, a
majority had underlying diseases or predisposing conditions, and the leg was most
often affected. Wound cultures were taken in 343 episodes and 56 grew group A
streptococci (GAS), 53 grew group G streptococci (GGS), 11 grew group C
streptococci (GCS), and 153 grew Staphylococcus aureus. Blood cultures were drawn
in 49 % of episodes and 50 cultures were positive with GGS as the most common
finding (21 cultures) followed by GAS in 13, group B streptococci in 5, S. aureus
in 4, and GCS in 3 cultures. In 45 % of episodes, patients received antibiotics
with activity against S. aureus. CONCLUSIONS: GGS is the most common
streptococcus isolated in erysipelas and the role of S. aureus in erysipelas
remains elusive.
PMID- 26424183
TI - Health-related quality of life measurement in chronic liver disease patients.
AB - BACKGROUND AND OBJECTIVE: Health-related quality of life (HRQOL) is an important
health indicator in medical outcome research and clinical practice. This issue
tends to attract even more attention with the recent improvements of patient
survival after liver transplantation. This review article aims at providing a
deeper insight into practices used for evaluating HRQOL in chronic liver diseases
(CLDs) and especially cirrhosis patients during different stages of the disease
including liver transplantation. MATERIALS AND METHODS: A systematic review of
the MEDLINE database and Cochrane library was conducted. A search using the
Medical Subject Headings (MeSH) major terms "liver disease" AND "quality of life"
was applied for the period from 1966 to 2012. RESULTS: Our review identified 1483
publications. The searched showed that significant increase of publications (from
362 to 1018) was observed during last decade (period 2003-2012) in comparison
with previous. The majority of publications were in English (n=1179). The
literature search and analysis provided information on the most common generic
and disease-specific HRQOL instruments, which are used in CLD patients: Medical
Outcomes Study Short Form-36, the National Institute of Diabetes and Digestive
and Kidney Diseases Quality of Life questionnaire, the Chronic Liver Disease
questionnaire, the Liver Disease Quality of Life questionnaire, and other.
CONCLUSIONS: Quality of life instruments are potentially powerful tools for
evaluating the functional status, presenting gains of treatment and reflecting
patients' ability to return to a normal lifestyle in CLD patients. More attention
should be paid by clinicians for integrated use of clinical tests together with
HRQOL instruments in liver transplantation for establishing the reference levels
of mental, physical, and role-social functioning.
PMID- 26424184
TI - Left ventricular function by speckle-tracking echocardiography in patients with
low-T3 syndrome and acute myocardial infarction.
AB - BACKGROUND AND OBJECTIVE: Low-T3 syndrome is common in patients with acute
myocardial infarction (AMI). Recent experimental and clinical data have suggested
a potential negative impact of low-T3 syndrome on myocardial function in patients
with AMI. The aim of this study was to assess left ventricular (LV) myocardial
function in patients with low-T3 syndrome and to investigate the association
between hormonal profile and the severity of LV dysfunction using speckle
tracking echocardiography (STE). MATERIALS AND METHODS: In 130 patients with
first-onset ST-segment elevation acute myocardial infarction (STEMI),
conventional 2D and speckle-tracking echocardiography within 48-72h after the
hospitalization was performed, and blood samples for TSH, fT4, fT3, and anti-TPO
levels were obtained to investigate thyroid hormone production within 24h and on
the fourth day after the onset of STEMI symptoms. RESULTS: The patients were
divided into two groups according to their serum level of fT3: group 1 with fT3
concentration below 3.2pmol/L (n=34) and group 2 with normal fT3 (>3.2pmol/L)
level (n=96). LV ejection fraction (EF) tended to be lower in the low fT3 group.
The systolic longitudinal strain did not differ between the groups, but the late
diastolic longitudinal strain rate was lower in group 1 (P=0.011). The systolic
basal LV rotation positively correlated with the level of fT3 (r=0.4; P<0.001),
while a negative correlation was detected between myocardial rotational
parameters - systolic apical rotation (r=-0.2; P<0.05), torsion (r=-0.3;
P<0.001), and diastolic apical rotation rate (r=-0.3; P<0.01) - and fT3 levels.
CONCLUSIONS: The late diastolic longitudinal LV strain rate and LV rotation
evaluated by speckle-tracking echocardiography were impaired in patients with low
T3 syndrome after AMI.
PMID- 26424185
TI - Comparison of the improvement in myocardial perfusion and function in cases of
rapid and slow electrocardiographic stage dynamics between patients with TIMI-3
flow after primary angioplasty for acute myocardial infarction.
AB - BACKGROUND AND OBJECTIVE: Post-PCI TIMI flow grade 3 in infarct-related artery
not always is associated with follow-up improvement in myocardial perfusion and
function. We compared the improvement in myocardial perfusion and function in
cases of rapid and slow electrocardiographic (ECG) stage dynamics between
patients with TIMI-3 flow after primary angioplasty for acute myocardial
infarction (MI). MATERIALS AND METHODS: Ten patients with post-PCI TIMI-3 flow
were divided into group A (n=50, no rapid change of ECG stages) and group B
(n=50, with a >=2 ECG stages per 2 days change rate). RESULTS: There were no
significant changes after 3 months in scintigraphic (ejection fraction 44.6+/
9.3% vs. 42.0+/-3.4%, P=0.4; perfusion deficit severity 3.0+/-0.7 vs. 2.3+/-0.8,
P=0.1) and echocardiographic (dysfunction score 1.9+/-0.2 vs. 1.6+/-0.5, P=0.2)
data in group A. Scintigraphic data improved (ejection fraction 34.6+/-3.9% vs.
52.0+/-7.3, P=0.03; perfusion deficit severity 2.8+/-0.6 vs. 1.5+/-0.8, P=0.03)
and changes in echocardiographic data were of borderline significance
(dysfunction score 1.8+/-0.2 vs. 1.4+/-0.4, P=0.06) in group B. CONCLUSIONS:
There was not any change in myocardial perfusion and function in a case of slow
change of ECG stages after reached post-PCI TIMI flow grade 3, while myocardial
perfusion improved and function tended to improve in a case of the rate at least
two ECG stages in 2 days after primary angioplasty for acute MI.
PMID- 26424186
TI - Prevalence and etiology of midfacial fractures: a study of 799 cases.
AB - BACKGROUND AND OBJECTIVE: The prevalence and etiology of midfacial fractures
varies among countries. Until now, knowledge about such type of injuries in the
region of the Baltic countries was rather scarce. The purpose of the study was to
analyze the prevalence, etiology and localization of midfacial fractures treated
at the Vilnius University Hospital Zalgiris Clinic, Vilnius, Lithuania. MATERIALS
AND METHODS: The medical records of patients treated for midfacial fractures
during the period January 2005 to December 2010 were analyzed for gender, age
distribution, frequency and type of injury, cause of fractures, consciousness
status and alcohol abuse during trauma. RESULTS: The records of 799 patients were
analyzed. The male-to-female ratio was 4.4:1. The mean age of the patients was
33.16+/-14.0 years (min 1, max 87). As much as 68.8% of injuries were zygomatic
fractures, 27.9% were maxillary, and 3.3% were isolated orbital floor fractures.
The most frequent causes for injury were interpersonal violence (64%), followed
by falls (16.3%) and traffic accidents (8.3%). Most midfacial fractures (65.3%)
occurred between April and October (P<0.05), on weekends (58.2%; P<0.05) and at
night (62.0%; P<0.05). In 14%, trauma reports indicated the abuse of alcohol.
More often such persons received more than one midfacial bone fracture (P<0.05)
concurrently. CONCLUSIONS: This study revealed that the main cause of midfacial
fractures was assault. Male patients, aged 15-34 years, more often sustain
midfacial fractures. Preventive health care programs should seek measures in the
reduction of aggression and violence in close future involving family, school and
community institutions.
PMID- 26424187
TI - Oral bony outgrowths: prevalence and genetic factor influence. Study of twins.
AB - OBJECTIVE: The aim of the study was to verify the influence of a genetic factor
on the etiology of oral bony outgrowths and to determine the prevalence and type
of oral bony outgrowths (tori and exostoses) among a group of Lithuanian twins.
MATERIALS AND METHODS: In total, 162 twins (81 twin pairs) were analyzed for the
presence or absence, type, and size of oral bony outgrowths. Statistical analysis
was carried out to find the prevalence of bony protuberances and the relationship
between zygosity and occurrence of oral bony enlargements. Zygosity of twins was
confirmed by DNA analysis. RESULTS: 59.9% of the subjects had oral bony
outgrowths. Mandibular tori were found in 56.8% and palatal tori in 1.8% of the
sample. Palatal exostoses and mandibular exostoses were present in 1.8% and 3.1%
of the sample, respectively, whereas maxillary exostoses were not found. A higher
percentage of tori and exostoses were found in the group of older subjects (>18
years old, p=0.025). No significant difference was found between men and women in
the prevalence of bony outgrowths. High kappa and r values (0.91+/-0.062) showed
very good concordance of oral bony outgrowths between monozygotic and moderate
concordance (0.58+/-0.141) between dizygotic co-twins (p<0.001). The calculation
of heritability estimate verifies dominant influence of genetic factor on the
etiology of oral bony outgrowths (h(2)=0.658). CONCLUSION: The most common bony
outgrowth was torus mandibularis. Our results show that the genetic factor is
dominant in the etiology of oral bony outgrowths.
PMID- 26424188
TI - Impact of left ventricular function on health-related quality of life in coronary
artery disease patients.
AB - OBJECTIVE: The aim of the study was to investigate the relation between health
related quality of life (HRQoL) and left ventricular systolic and diastolic
function parameters in stable coronary artery disease (CAD) patients with mild
and moderate heart failure. MATERIALS AND METHODS: This study included 758 CAD
patients. Left ventricular ejection fraction (LVEF) and ratio of peak velocities
of early (E) and late (A) diastolic mitral inflow, ratio E/A, deceleration time,
isovolumic relaxation time were assessed. Patients completed the SF-36
questionnaire. RESULTS: There were no strong and significant associations between
echocardiographic measures and HRQoL in NYHA I-II class patients. In NYHA III
class in univariate linear regression analyses significant associations were
found between LVEF and physical functioning (beta=0.230, P=0.009) and role
limitations due to physical problems (beta=0.230, P=0.009) and these associations
remain significant after adjustment for age, gender, hypertension, angina
pectoris class, nitrate, ACE inhibitors and diuretics use. E/A ratio was
significantly associated only with mental health domain (beta=0.188, P=0.048),
and this association remains significant after all adjustments. CONCLUSIONS: In
stable CAD patients with NYHA I-II functional class HRQoL was not strongly
associated with left ventricular function; in NYHA III functional class patients'
greater systolic function mainly was associated with better physical health and
better diastolic function, with better mental health.
PMID- 26424189
TI - Management of coronary artery disease patients in Latvia compared with practice
in Central-Eastern Europe and globally: analysis of the CLARIFY registry.
AB - BACKGROUND AND OBJECTIVE: Management of outpatients with stable coronary artery
disease (CAD) is important in secondary prevention. The objective was to describe
differences in the characteristics of CAD patients in Latvia compared with other
countries. MATERIALS AND METHODS: CLARIFY is an ongoing international,
prospective, observational, longitudinal registry of outpatients with CAD. Data
regarding treated outpatients with established CAD from the CLARIFY registry in
Latvia (n=120) were compared with those from the rest of Central-Eastern Europe
(CEE) (n=2888) and worldwide (n=33,163). RESULTS: Patients in Latvia had a larger
waist circumference (101 [95-109] vs. 99 [91-106] in CEE, 96.5 [88-105]cm
worldwide; P=0.023 and P<0.001, respectively) and higher blood pressure
(systolic: 138.28+/-17.13 vs. 133.77+/-16.47 in CEE and 130.97+/-16.65mm Hg
worldwide, P=0.003 and P<0.001; diastolic: 82.98+/-8.58 vs. 80.01+/-9.61 in CEE
and 77.22+/-9.97mm Hg worldwide, P<0.001 and P<0.001, respectively). Body mass
index in Latvia did not differ significantly from that in CEE (P=0.422), but was
higher than worldwide (28.8 [26.2-32.0] vs. worldwide 27.3 [24.8-30.3]kg/m(2),
P<0.001). The history of percutaneous coronary intervention was more frequent in
Latvia (74.17% vs. 59.34% in CEE and 58.61% worldwide, P=0.001 and P<0.001,
respectively). Latvian patients more frequently used aspirin (97.50% in Latvia
vs. 89.75% in CEE and 87.64% worldwide, P=0.005 and P=0.001, respectively).
CONCLUSIONS: Latvian CAD patients are well managed in terms of aspirin use and
frequency of percutaneous coronary intervention. Control of obesity and high BP
is poorer and needs further improvement.
PMID- 26424190
TI - Body physique and dominant somatotype in elite and low-profile athletes with
different specializations.
AB - BACKGROUND AND OBJECTIVE: Somatotyping is helpful in sports in which the body
shape could influence the resulting performance. The purpose of this study was to
determine the somatotype of high profile Lithuanian athletes in kayaking,
basketball and football and to compare between disciplines and with low level
sportsmen of the same age. MATERIALS AND METHODS: A total of 72 young male
sportsmen aged from 18 to 24 years were divided into three groups (kayakers,
basketball and football players). Each group contained almost equal numbers of
low level and elite, international level sportsmen. Anthropometric measurements
of the players were used to establish somatotypes. RESULTS: The greatest
difference was observed in the mesomorphic component of elite kayakers compared
to the low profile sportsmen. Mesomorphy could also be used to predict sport
ability. The range of mesomorphy for elite footballers was from 0 to 4.6, for
basketball players from 4.6 to 5.9, and for kayaking, from 5.9 and higher.
Individual groups of elite sportsmen displayed different modes of somatotype. The
kayakers were predominantly endomorphic; the basketball players mostly
endomorphic and the footballers most often ectomorphic. No distinguishable
patterns of somatotype were displayed by the low level sportsmen. CONCLUSIONS:
Morphometric characteristics of the athlete's body and the fractional somatotype
can be used as guiders and markers of the chosen sport and method of training.
The results emphasize the necessity for a specific somatotype to reach a high
profile in the selected area of sport and thus support morphometric oriented
studies. Further studies could elucidate differentiation by age and sex.
PMID- 26424191
TI - Temperature influencing permeation pattern of alfuzosin: an investigation using
DoE.
AB - BACKGROUND AND OBJECTIVE: There has been relatively little investigation of the
effect of temperature on skin permeation compared to other methods of penetration
enhancement. A principal physicochemical factor which controls the passive
diffusion of a solute from a vehicle into the skin arises from the skin
temperature. The aim of this ex vivo study was to probe into the effect of heat
on transdermal absorption of alfuzosin hydrochloride from ethyl cellulose
polyvinyl pyrrolidone (EC-PVP) based transdermal systems. MATERIALS AND METHODS:
Principles of design of experiment (DoE) were used to systematically study the
influence of temperature on transdermal permeation of alfuzosin. Ex vivo
transdermal permeation studies were carried out at varied donor compartment
temperatures. Permeation data analysis was carried out and activation energy for
transdermal permeation was estimated. RESULTS: Temperature found to enhance ex
vivo permeation parameters of alfuzosin hydrochloride from its transdermal
systems. It was also noted that chemical permeation enhancers potentiate
permeation enhancing effect of temperature. The permeation flux values
approximately doubled after exposure to 45 degrees C. The activation energy for
transdermal permeation was found lower for the runs with chemical permeation
enhancers indicating existence of a lower energy barrier in the presence of
chemical permeation enhancers. CONCLUSION: The method reported here is a simple
and useful tool for studying the effect of heat on percutaneous absorption. Such
temperature dependent enhancement of flux can be more pronounced at skin surface
temperatures >45 degrees C.
PMID- 26424192
TI - An automated fitting procedure and software for dose-response curves with
multiphasic features.
AB - In cancer pharmacology (and many other areas), most dose-response curves are
satisfactorily described by a classical Hill equation (i.e. 4 parameters
logistical). Nevertheless, there are instances where the marked presence of more
than one point of inflection, or the presence of combined agonist and antagonist
effects, prevents straight-forward modelling of the data via a standard Hill
equation. Here we propose a modified model and automated fitting procedure to
describe dose-response curves with multiphasic features. The resulting general
model enables interpreting each phase of the dose-response as an independent dose
dependent process. We developed an algorithm which automatically generates and
ranks dose-response models with varying degrees of multiphasic features. The
algorithm was implemented in new freely available Dr Fit software
(sourceforge.net/projects/drfit/). We show how our approach is successful in
describing dose-response curves with multiphasic features. Additionally, we
analysed a large cancer cell viability screen involving 11650 dose-response
curves. Based on our algorithm, we found that 28% of cases were better described
by a multiphasic model than by the Hill model. We thus provide a robust approach
to fit dose-response curves with various degrees of complexity, which, together
with the provided software implementation, should enable a wide audience to
easily process their own data.
PMID- 26424193
TI - Rising Incidence of Clostridium difficile Related Discharges among Hospitalized
Children in the United States.
AB - Using a national database, we report an increasing trend in Clostridium difficile
incidence among hospitalized children in the United States from 2003 to 2012. The
incidence rate of CDI increased from 24.0 to 58.0 per 10,000 discharges per year
(P<0.001) across all age groups, with the greatest increase in children 15 years
and older. Infect. Control Hosp. Epidemiol. 2015;37(1):104-106.
PMID- 26424194
TI - New genes drive the evolution of gene interaction networks in the human and mouse
genomes.
AB - BACKGROUND: The origin of new genes with novel functions creates genetic and
phenotypic diversity in organisms. To acquire functional roles, new genes must
integrate into ancestral gene-gene interaction (GGI) networks. The mechanisms by
which new genes are integrated into ancestral networks, and their evolutionary
significance, are yet to be characterized. Herein, we present a study
investigating the rates and patterns of new gene-driven evolution of GGI networks
in the human and mouse genomes. RESULTS: We examine the network topological and
functional evolution of new genes that originated at various stages in the human
and mouse lineages by constructing and analyzing three different GGI datasets. We
find a large number of new genes integrated into GGI networks throughout
vertebrate evolution. These genes experienced a gradual integration process into
GGI networks, starting on the network periphery and gradually becoming highly
connected hubs, and acquiring pleiotropic and essential functions. We identify a
few human lineage-specific hub genes that have evolved brain development-related
functions. Finally, we explore the possible underlying mechanisms driving the GGI
network evolution and the observed patterns of new gene integration process.
CONCLUSIONS: Our results unveil a remarkable network topological integration
process of new genes: over 5000 new genes were integrated into the ancestral GGI
networks of human and mouse; new genes gradually acquire increasing number of
gene partners; some human-specific genes evolved into hub structure with critical
phenotypic effects. Our data cast new conceptual insights into the evolution of
genetic networks.
PMID- 26424195
TI - Costs of HIV/AIDS treatment in Indonesia by time of treatment and stage of
disease.
AB - BACKGROUND: We report an economic analysis of Human Immunodeficiency Virus (HIV)
care and treatment in Indonesia to assess the options and limitations of costs
reduction, improving access, and scaling up services. METHODS: We calculated the
cost of providing HIV care and treatment in a main referral hospital in West
Java, Indonesia from 2008 to 2010, differentiated by initiation of treatment at
different CD4 cell count levels (0-50, 50-100, 100-150, 150-200, and >200
cells/mm(3)); time of treatment; HIV care and opportunistic infections cost
components; and the costs of patients for seeking and undergoing care.
DISCUSSION: Before antiretroviral treatment (ART) initiation, costs were
dominated by laboratory tests (>65 %), and after initiation, by antiretroviral
drugs (>=60 %). Average treatment costs per patient decreased with time on
treatment (e.g. from US$580 per patient in the first 6 month to US$473 per
patient in months 19-24 for those with CD4 cell counts under 50 cells/mm(3)).
Higher CD4 cell counts at initiation resulted in lower laboratory and
opportunistic infection treatment costs. Transportation cost dominated the costs
of patients for seeking and undergoing care (>40 %). CONCLUSIONS: Costs of
providing ART are highest during the early phase of treatment. Costs reductions
can potentially be realized by early treatment initiation and applying
alternative laboratory tests with caution. Scaling up ART at the community level
in certain high prevalence settings may improve early uptake, adherence, and
reduce transportation costs.
PMID- 26424197
TI - Biology and management of sugarcane yellow leaf virus: an historical overview.
AB - Sugarcane yellow leaf virus (SCYLV) is one of the most widespread viruses causing
disease in sugarcane worldwide. The virus has been responsible for drastic
economic losses in most sugarcane-growing regions and remains a major concern for
sugarcane breeders. Infection with SCYLV results in intense yellowing of the
midrib, which extends to the leaf blade, followed by tissue necrosis from the
leaf tip towards the leaf base. Such symptomatic leaves are usually characterized
by increased respiration, reduced photosynthesis, a change in the ratio of hexose
to sucrose, and an increase in starch content. SCYLV infection affects carbon
assimilation and metabolism in sugarcane, resulting in stunted plants in severe
cases. SCYLV is mainly propagated by planting cuttings from infected stalks.
Phylogenetic analysis has confirmed the worldwide distribution of at least eight
SCYLV genotypes (BRA, CHN1, CHN3, CUB, HAW, IND, PER, and REU). Evidence of
recombination has been found in the SCYLV genome, which contains potential
recombination signals in ORF1/2 and ORF5. This shows that recombination plays an
important role in the evolution of SCYLV.
PMID- 26424196
TI - The Assessment and Non-Pharmacologic Treatment of Procedural Pain From Infancy to
School Age Through a Developmental Lens: A Synthesis of Evidence With
Recommendations.
AB - The 2011 IOM report stated that pain management in children is often lacking
especially during routine medical procedures. The purpose of this review is to
bring a developmental lens to the challenges in assessment and non-pharmacologic
treatment of pain in young children. METHOD: A synthesis of the findings from an
electronic search of PubMed and the university library using the keywords pain,
assessment, treatment, alternative, complementary, integrative, infant, toddler,
preschool, young, pediatric, and child was completed. A targeted search
identified additional sources for best evidence. RESULTS: Assessment of
developmental cues is essential. For example, crying, facial expression, and body
posture are behaviors in infancy that indicate pain: however in toddlers these
same behaviors are not necessarily indicative of pain. Preschoolers need
observation scales in combination with self-report while for older children self
report is the gold standard. Pain management in infants includes swaddling and
sucking. However for toddlers, preschoolers and older children, increasingly
sophisticated distraction techniques such as easily implemented non-pharmacologic
pain management strategies include reading stories, watching cartoons, or
listening to music. DISCUSSION: A developmental approach to assessing and
treating pain is critical. Swaddling, picture books, or blowing bubbles are easy
and effective when used at the appropriate developmental stage and relieve both
physical and emotional pain. Untreated pain in infants and young children may
lead to increased pain perception and chronic pain in adolescents and adults.
Continued research in the non-pharmacological treatment of pain is an important
part of the national agenda.
PMID- 26424198
TI - Complete genome sequence of a novel endornavirus isolated from hot pepper.
AB - The complete genome of a putative new endornavirus infecting hot peppers
(Capsicum annuum) was determined to be 14,729 nt in size, including 12 cytosines
at the 3' end. The hot pepper-infecting virus has the highest nucleotide sequence
similarity (94% query cover and 72% identity) to bell pepper endornavirus (BPEV)
isolated from the cultivar Yolo Wonder in the USA (GenBank accession no.
JN019858). The putative single, large open reading frame encodes a 4,884-amino
acid-long polyprotein that contains four putative functional domains: a viral
methyltransferase, a viral RNA helicase, a glycosyltransferase, and an RNA
dependent RNA polymerase. A phylogenetic tree based on whole polyprotein
sequences confirmed the close evolutionary relationship of the studied
endornavirus to BPEV. The hot pepper-infecting virus also has a nick at nt
position 975. Taken together, these results suggest that this virus belongs to a
new species in the genus Endornavirus (family Endornaviridae), for which the name
hot pepper endornavirus (HPEV) is proposed.
PMID- 26424199
TI - Key Findings from Preclinical and Clinical Drug Interaction Studies Presented in
New Drug and Biological License Applications Approved by the Food and Drug
Administration in 2014.
AB - Regulatory approval documents contain valuable information, often not published,
to assess the drug-drug interaction (DDI) profile of newly marketed drugs. This
analysis aimed to systematically review all drug metabolism, transport,
pharmacokinetics, and DDI data available in the new drug applications and
biologic license applications approved by the U.S. Food and Drug Administration
in 2014, using the University of Washington Drug Interaction Database, and to
highlight the significant findings. Among the 30 new drug applications and 11
biologic license applications reviewed, 35 new molecular entities (NMEs) were
well characterized with regard to drug metabolism, transport, and/or organ
impairment and were fully analyzed in this review. In vitro, a majority of the
NMEs were found to be substrates or inhibitors/inducers of at least one drug
metabolizing enzyme or transporter. In vivo, when NMEs were considered as victim
drugs, 16 NMEs had at least one in vivo DDI study with a clinically significant
change in exposure (area under the time-plasma concentration curve or Cmax ratio
>=2 or <=0.5), with 6 NMEs shown to be sensitive substrates of cytochrome P450
enzymes (area under the time-plasma concentration curve ratio >=5 when
coadministered with potent inhibitors): paritaprevir and naloxegol (CYP3A),
eliglustat (CYP2D6), dasabuvir (CYP2C8), and tasimelteon and pirfenidone
(CYP1A2). As perpetrators, seven NMEs showed clinically significant inhibition
involving both enzymes and transporters, although no clinically significant
induction was observed. Physiologically based pharmacokinetic modeling and
pharmacogenetics studies were used for six and four NMEs, respectively, to
optimize dosing recommendations in special populations and/or multiple impairment
situations. In addition, the pharmacokinetic evaluations in patients with hepatic
or renal impairment provided useful quantitative information to support drug
administration in these fragile populations.
PMID- 26424200
TI - Integrating neuroscience into psychiatric residency training.
PMID- 26424201
TI - VapeCons: E-cigarette user conventions.
AB - INTRODUCTION: E-cigarette 'vaping conventions' provide a venue for user social
networking, parties, and 'try before you buy' access to a wide range of e
cigarette products. This study identifies and describes vaping conventions,
raising awareness of this potentially problematic practice. METHODS: Conventions
were identified via Google searches in April and May 2014 and August 2015.
Details captured included location, sponsors, admission cost, event features, and
promotions. RESULTS: 41 distinct organizations have planned 90 vaping conventions
in 37 different locations since 2010. Conventions promoted access to a wide range
of product vendors, seminars, social interactions with other users, parties,
gifts, vaping contests, and other events. E-cigarette use at conventions was
encouraged. CONCLUSIONS: Vaping conventions promote e-cigarette use and social
norms without public health having a voice to educate attendees about negative
consequences of use. Future research should focus on the effects of attending
these conventions on attendees and on indoor air quality in vapor-filled
convention rooms.
PMID- 26424202
TI - Child toy safety: An interdisciplinary approach to unravel the microbiological
hazard posed by soap bubbles.
AB - In 2012 some children developed sepsis after playing together with a soap bubble
toy. Microbiological testing revealed heavy contamination of the soap solution,
which reasonably represented the vehicle of infection. We investigated the issue
with a multidisciplinary approach: review of toy safety legislation;
microbiological testing of additional samples; query of the RAPEX database for
non-compliant soap bubbles; identification of major manufacturing districts.
Microbiological contamination of industrial soap bubbles was widespread. Sixty
three notifications of batches contaminated by environmental microorganisms and
opportunistic pathogens had been reported. The Chinese had a virtual monopoly of
the soap bubble market. We identified two main manufacturing districts in
Guangdong Province, both notable for degradation of their water resources. The
use of untreated water for the industrial production of soap bubbles may explain
the bacterial contamination. Existing legislation provides an unsatisfactory
approach for managing microbiological hazards in sensitive toy categories and for
identifying responsible parties in import and export of the products.
PMID- 26424203
TI - A comparative analysis of how the media in the United Kingdom and India
represented the emergence of NDM-1.
AB - Research papers on New Delhi metallo-beta-lactamase (NDM-1) provoked considerable
but very different media coverage in the United Kingdom (UK) and India. We
describe how the media represented this research using qualitative thematic
analysis of contemporary coverage by daily newspapers in the UK and India. Fifty
four UK and 187 Indian articles mentioned NDM-1, describing it as the 'new super
superbug' resistant to most antibiotics. They emphasised the role of medical
tourism to the Indian subcontinent. In both countries, blame was framed
abstractly as arising from the general misuse of antibiotics. In India,
controversy about using New Delhi to name the organism dominated coverage, with
officials seeking to discredit the two studies and media coverage characterised
by denial and outrage, developing into theories of conspiracies to undermine
tourism. Researchers must seek to anticipate the way that their work may be
reported and proactively engage with the media to maximise the public health
impact of their findings.
PMID- 26424204
TI - Time for a regional alcohol policy - A literature review of the burden of
normative alcohol use in the Caribbean.
AB - Alcohol use is deeply engrained in the socio-cultural fabric of the Caribbean
where heavy episodic drinking is an accepted and common drinking pattern. This
article aims to create awareness of the tremendous negative impact on population
health in the English-speaking Caribbean from culturally customary levels of
alcohol consumption. It advocates for the urgent development and implementation
of a regional alcohol policy in the English-speaking Caribbean, and emphasizes
the importance of crafting and implementing the policy without cultural offence.
PMID- 26424205
TI - Minimizing Aryloxy Elimination in Rh(I) -Catalyzed Asymmetric Hydrogenation of
beta-Aryloxyacrylic Acids using a Mixed-Ligand Strategy.
AB - The first example of efficient asymmetric hydrogenation of challenging beta
aryloxyacrylic acids was realized using a Rh(I) -complex based on the
heterocombination of a readily available chiral monodentate secondary phosphine
oxide (SPO) and an achiral monodentate phosphine ligand as the catalyst.
Excellent enantioselectivities (92->99 % ee) were achieved for a wide variety of
chiral beta-aryloxypropionic acids with minor aryloxy elimination in most cases.
The resultant products were readily transformed into biologically active
compounds through simple synthetic manipulations.
PMID- 26424206
TI - Antioxidant and anticoagulant activity of sulfated polysaccharide from Gracilaria
debilis (Forsskal).
AB - Sulfated polysaccharide was isolated from Gracilaria debilis and purified through
gel chromatography and their molecular weight was determined through AGE and
PAGE. The total sugars in the crude, fractionated and purified polysaccharide
were estimated as 52.65%, 59.70% and 67.60%, respectively. The ash and moisture
content of crude and purified polysaccharide was found to be 14.2% and 23.5% and
the polysaccharide was free from protein contamination. The sulfate and uronic
acid contents in the crude, fractionated and purified were estimated as 14.08%,
15.33% and 16.01% and 10.12%, 13.56%, 16.70%. The elemental composition including
carbon (crude - 23.12%, purified - 21.05%), hydrogen (crude - 3.4%, purified -
4.13%) and nitrogen (crude - 1.22%, purified - 0.56%) were also analyzed. The
anticoagulant activity of the sulfated polysaccharide through APTT and PT was
estimated at 14.11 and 8.23IU/mg. The purified polysaccharide with the molecular
mass of 20kDa showed highest antioxidant activity (38.57%, 43.48% and 38.88%) in
all the assays tested such as DPPH hydroxyl radical, superoxide radical, hydroxyl
radical scavenging activities and the structural property was analyzed through FT
IR and (1)H NMR spectrum. The results together suggest that the isolated low
molecular weight sulfated polysaccharide will demonstrate as a enormously
available alternative natural source of antioxidant for industrial uses.
PMID- 26424207
TI - Synthesis, characterization, DNA binding, DNA cleavage, protein binding and
cytotoxic activities of Ru(II) complexes.
AB - We report on the synthesis of novel Ru(II) compounds (Ru-1 to Ru-8) bearing R
pdc, 4-Cl-pbinh ligands (where R=4-CF3, 4-F, 4-OH pdc=3-phenyl-5-(1H-pyrrol-2-yl)
4,5-dihydro-1H-pyrazole-1-carbothioamide, pbinh=phenoxybenzylidene isonicotinyl
hydrazides) and their in vitro antitumor activity toward the cell lines murine
leukemia L1210, human lymphocyte CEM, human epithelial cervical carcinoma HeLa,
BEL-7402 and Molt4/C8. Some of the complexes exhibited more potent
antiproliferative activity against cell lines than the standard drug cisplatin.
Ruthenium complex Ru-2 displayed potent cytotoxicity with than that of cisplatin.
DNA-binding, DNA cleavage and protein binding properties of ruthenium complexes
with these ligands are reported. Interactions of these ruthenium complexes with
DNA revealed an intercalative mode of binding between them. Synchronous
fluorescence spectra proved that the interaction of ruthenium complexes with
bovine serum albumin (BSA) resulted in a conformational change of the latter.
PMID- 26424209
TI - Plasma biomarker signature associated with improved survival in advanced non
small cell lung cancer patients on linifanib.
AB - OBJECTIVES: Linifanib, a potent and selective inhibitor of the tyrosine kinase
activity of vascular endothelial growth factor and platelet-derived growth factor
receptors, has clinical activity in advanced non-small cell lung cancer (NSCLC)
both as monotherapy in the relapsed setting or with carboplatin and paclitaxel in
the first-line setting. Though benefit was observed in unselected patient
populations, identification of predictive biomarkers is critical for further
development of this novel agent. MATERIALS AND METHODS: Data from 4 randomized
studies in relapsed NSCLC with linifanib (n=116) or other treatments (n=125) were
examined in an exploratory analysis to identify a biomarker profile predictive of
favorable survival. RESULTS: A signature combining the established tumor markers
carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) was
predictive of a favorable outcome. This signature was associated with improved
survival in patients receiving linifanib monotherapy (hazard ratio [HR]=0.51 vs
signature negative; p=0.002), but not in those receiving other anti-cancer
treatments (p=0.716). This signature was validated on baseline plasma samples
from patients enrolled in a randomized trial of daily linifanib 7.5 mg, linifanib
12.5 mg, or placebo added to first-line carboplatin and paclitaxel chemotherapy
for advanced, nonsquamous NSCLC. Only linifanib-treated signature-positive
patients had significant improvement in progression-free survival (PFS). Median
PFS with placebo was 5.2 months versus 10.2 months (HR=0.49, p=0.049) for those
receiving linifanib 7.5mg, and 8.3 months (HR=0.38, p=0.029) for linifanib 12.5
mg. Overall survival for signature-positive patients was 11.3 months with
placebo, 12.5 months with linifanib 7.5mg (HR=1.02, p=0.758), and 17.4 months
with linifanib 12.5 mg (HR=0.54, p=0.137). CONCLUSION: This baseline plasma
biomarker signature is associated with improved outcome in advanced NSCLC
patients receiving linifanib. Utility of the biomarker signature in patient
selection for linifanib therapy in NSCLC merits evaluation in larger, prospective
trials that are powered to detect a survival benefit.
PMID- 26424208
TI - From genotype to phenotype: Are there imaging characteristics associated with
lung adenocarcinomas harboring RET and ROS1 rearrangements?
AB - INTRODUCTION: Recurrent gene rearrangements are important drivers of oncogenesis
in non-small cell lung cancers. RET and ROS1 rearrangements are each found in 1
2% of lung adenocarcinomas and represent distinct molecular subsets. This study
assessed the computed tomography (CT) imaging features of patients with RET- and
ROS1-rearranged lung cancers. METHODS: Eligible patients included pathologically
confirmed lung adenocarcinomas of any stage with a RET or ROS1 rearrangement via
fluorescence in-situ hybridization or next-generation sequencing, and available
pre-treatment baseline imaging for review. A cohort of EGFR-mutant lung cancers
was identified as a control group. CT features assessed included location,
consistency, contour, presence of cavitation, and calcification of the primary
tumor. Presence of an effusion, lung metastases, adenopathy and extrathoracic
disease were recorded. The Wilcoxon rank-sum/Kruskal-Wallis and Fisher's exact
tests were used to compare features between groups. RESULTS: 73 patients with
lung adenocarcinomas were identified: 17 (23%) with ROS1 fusions, 25 (34%) with
RET fusions and 31 (43%) with EGFR mutations. ROS1-rearranged lung cancers were
more likely to present as peripheral tumors in comparison to EGFR-mutant lung
cancers (32% vs. 65%, p=0.04). RET-rearranged lung cancers did not significantly
differ from EGFR-mutant lung cancers radiographically. The consistency of the
primary lesion for RET and ROS fusions and EGFR mutations were most frequently
solid and spiculated. CONCLUSIONS: Lung adenocarcinomas with RET and ROS1 fusions
share many radiographic features and those with ROS1 fusions are more likely to
present as peripheral lesions in comparison to EGFR-mutant lung cancers.
PMID- 26424210
TI - The Third Pillar.
PMID- 26424211
TI - Opportunities in Reform: Bioethics and Mental Health Ethics.
AB - Last year marks the first year of implementation for both the Patient Protection
and Affordable Care Act and the Mental Health Parity and Addiction Equity Act in
the United States. As a result, healthcare reform is moving in the direction of
integrating care for physical and mental illness, nudging clinicians to consider
medical and psychiatric comorbidity as the expectation rather than the exception.
Understanding the intersections of physical and mental illness with autonomy and
self-determination in a system realigning its values so fundamentally therefore
becomes a top priority for clinicians. Yet Bioethics has missed opportunities to
help guide clinicians through one of medicine's most ethically rich and
challenging fields. Bioethics' distancing from mental illness is perhaps best
explained by two overarching themes: 1) An intrinsic opposition between
approaches to personhood rooted in Bioethics' early efforts to protect the
competent individual from abuses in the research setting; and 2) Structural
forces, such as deinstitutionalization, the Patient Rights Movement, and managed
care. These two themes help explain Bioethics' relationship to mental health
ethics and may also guide opportunities for rapprochement. The potential role for
Bioethics may have the greatest implications for international human rights if
bioethicists can re-energize an understanding of autonomy as not only free from
abusive intrusions but also with rights to treatment and other fundamental
necessities for restoring freedom of choice and self-determination. Bioethics
thus has a great opportunity amid healthcare reform to strengthen the important
role of the virtuous and humanistic care provider.
PMID- 26424212
TI - Serum uric acid is associated with mortality and heart failure hospitalizations
in patients with complicated myocardial infarction: findings from the High-Risk
Myocardial Infarction Database Initiative.
AB - AIMS: Serum uric acid (SUA) levels are associated with poorer outcomes in healthy
cohorts and patients with stable and unstable coronary heart disease. We
investigated the relationship between SUA and clinical outcomes in subjects with
acute myocardial infarction (MI) complicated by reduced left ventricular (LV)
function, heart failure (HF), or both. METHODS AND RESULTS: Univariable and
multivariable Cox proportional hazards modelling was performed to study the
association of baseline SUA and all-cause mortality, cardiovascular (CV)
mortality, and HF hospitalization in an individual patient meta-analysis of four
merged large randomized trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT). Three
trials (excluding VALIANT) reported SUA, which was available in a total of 12 677
subjects. The ranges of SUA for quartiles I-IV were 45-280, 281-344, 345-420, and
420-1640 mmol/L, respectively. While almost 90% of patients in the lowest SUA
quartile were alive after a mean follow-up of 23 +/- 11 months, <70% were alive
in the highest SUA quartile. Compared with the lowest SUA quartile as reference,
hazard ratios (HRs) and 95% confidence intervals (CIs) of SUA quartiles III and
IV showed an increase in all-cause mortality [HR 1.18, 95% CI 0.95-1.46, and HR
1.36, 95% CI 1.11-1.67) and CV mortality (HR 1.27, 95% 1.01-1.61, and HR 1.47,
95% CI 1.17-1.83). SUA quartiles III and IV also exhibited increased HF
hospitalization (HR 1.22, 95% CI 1.09-1.36, and HR 1.28, 95% CI 1.14-1.43; P <
0.001 for all comparisons) in multivariable analyses. The addition of SUA was
associated with a significant improvement in reclassification to predict CV
mortality (net reclassification improvement 17.6%, 95% CI 14.9-20.5%, P < 0.001).
CONCLUSIONS: Elevated SUA is associated with poor outcomes in patients after MI
complicated by reduced LV function, HF, or both. The quantification of SUA, a low
cost routinely available biomarker, could improve risk stratification of patients
with complicated MI.
PMID- 26424213
TI - Effect of distal sugar and interglycosidic linkage of disaccharides on the
activity of proline rich antimicrobial glycopeptides.
AB - The effect of glycosylation on protein structure and function depends on a
variety of intrinsic factors including glycan chain length. We have analyzed the
effect of distal sugar and interglycosidic linkage of disaccharides on the
properties of proline-rich antimicrobial glycopeptides, formaecin I and drosocin.
Their glycosylated analogs-bearing lactose, maltose and cellobiose, as a glycan
side chain on their conserved threonine residue, were synthesized where these
disaccharides possess identical proximal sugar and vary in the nature of distal
sugar and/or interglycosidic linkage. The structural and functional properties of
these disaccharide-containing formaecin I and drosocin analogs were compared with
their corresponding monoglycosylated forms, beta-D-glucosyl-formaecin I and beta
D-glucosyl-drosocin, respectively. We observed neither major secondary structural
alterations studied by circular dichroism nor substantial differences in the
toxicity with mammalian cells among all of these analogs. The comparative
analyses of antibacterial activities of these analogs of formaecin I and drosocin
displayed that beta-D-maltosyl-formaecin I and beta-D-maltosyl-drosocin were more
potent than that of respective beta-D-Glc-analog, beta-D-cellobiosyl-analog and
beta-D-lactosyl-analog. Despite the differences in their antibacterial activity,
all the analogs exhibited comparable binding affinity to DnaK that has been
reported as one of the targets for proline-rich class of antibacterial peptides.
The comparative-quantitative internalization studies of differentially active
analogs revealed the differences in their uptake into bacterial cells. Our
results exhibit that the sugar chain length as well as interglycosidic linkage of
disaccharide may influence the antibacterial activity of glycosylated analogs of
proline-rich antimicrobial peptides and the magnitude of variation in
antibacterial activity depends on the peptide sequence.
PMID- 26424214
TI - Plasma Chemokine signature correlates with lung goblet cell hyperplasia in
smokers with and without chronic obstructive pulmonary disease.
AB - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung
and systemic inflammation as well as airway goblet cell hyperplasia (GCH). Mucin
production is activated in part by stimulation of the epidermal growth factor
(EGF) receptor pathway through neutrophils and macrophages. How circulating
cytokine levels relate to GCH is not clear. METHODS: We performed phlebotomy and
bronchoscopy on 25 subjects (six nonsmokers, 11 healthy smokers, and eight COPD
subjects FEV1 30-60 %). Six endobronchial biopsies per subject were performed.
GCH was measured by measuring mucin volume density (MVD) using stereological
techniques on periodic acid fast-Schiff stained samples. We measured the levels
of chemokines CXCL8/IL-8, CCL2/MCP-1, CCL7/MCP-3, CCL22/MCD, CCL3/MIP-1alpha, and
CCL4/MIP-1beta, and the cytokines IL-1, IL-4, IL-6, IL-9, IL-17, EGF, and
vascular endothelial growth factor (VEGF). Differences between groups were
assessed using one-way ANOVA, t test, or Chi squared test. Post hoc tests after
ANOVA were performed using Bonferroni correction. RESULTS: MVD was highest in
healthy smokers (27.78 +/- 10.24 MUL/mm(2)) compared to COPD subjects (16.82 +/-
16.29 MUL/mm(2), p = 0.216) and nonsmokers (3.42 +/- 3.07 MUL/mm(2), p < 0.0001).
Plasma CXCL8 was highest in healthy smokers (11.05 +/- 8.92 pg/mL) compared to
nonsmokers (1.20 +/- 21.92 pg/mL, p = 0.047) and COPD subjects (6.01 +/- 5.90
pg/mL, p = 0.366). CCL22 and CCL4 followed the same trends. There were no
significant differences in the other cytokines measured. When the subjects were
divided into current smokers (healthy smokers and COPD current smokers) and
non/ex-smokers (nonsmokers and COPD ex-smokers), plasma CXCL8, CCL22, CCL4, and
MVD were greater in current smokers. No differences in other cytokines were seen.
Plasma CXCL8 moderately correlated with MVD (r = 0.552, p = 0.003). DISCUSSION:
In this small cohort, circulating levels of the chemokines CXCL8, CCL4, and
CCL22, as well as MVD, attain the highest levels in healthy smokers compared to
nonsmokers and COPD subjects. These findings seem to be driven by current smoking
and are independent of airflow obstruction. CONCLUSIONS: These data suggest that
smoking upregulates a systemic pattern of neutrophil and macrophage
chemoattractant expression, and this correlates significantly with the
development of goblet cell hyperplasia.
PMID- 26424215
TI - Vasoactive Inotropic Score (VIS) as Biomarker of Short-Term Outcomes in
Adolescents after Cardiothoracic Surgery.
AB - Our aim was to evaluate the Vasoactive Inotropic Score (VIS) as a prognostic
marker in adolescents following surgery for congenital heart disease. This single
center retrospective chart review included patients 10-18 years of age, who
underwent cardiac surgery from 2009 to 2014. Hourly VIS was calculated for the
initial 48 postoperative hours using standard formulae and incorporating doses of
six pressors. The composite adverse outcome was defined as any one of death,
resuscitation or mechanical support, arrhythmia, infection requiring
antibacterial therapy, acute kidney injury or neurologic injury. Surgeries were
risk-stratified by the type of surgical repair using the validated STAT score.
Statistical analysis (SPSS 19.0) included Mann-Whitney U test, Chi-square test,
ROC curves, and binary regression analysis. Our cohort (n = 149) had a mean (SD)
age of 13.9 (2.4) years and included 97 (65.1 %) males. Maximal VIS at 24 and 48
h following surgery was significantly higher in subjects (n = 27) who suffered an
adverse outcome. Subjects with adverse outcome had longer bypass and cross-clamp
times, durations of stay in the hospital, and a higher rate of acute kidney
injury, compared to those (n = 122) without postoperative adverse outcomes. The
area under the ROC for maximum VIS at 24-48 h after surgery was 0.76, with
sensitivity, specificity, and positive and negative predictive values with 95 %
CI of 67 (48-82) %, 74 (70-77) %, and 36 (26-44) % and 91 (86-95) %,
respectively, at a cutoff >4.75. On binary logistic regression, maximum VIS on
second postoperative day remained significantly associated with adverse outcome
(OR 1.35; 95 % CI> 1.12-1.64, p = 0.002). Maximal VIS at 24 and 48 h correlated
significantly with length of stay and time to extubation. Maximal VIS on the
second postoperative day predicts adverse outcome in adolescents following
cardiac surgery. This simple yet robust prognostic indicator may aid in risk
stratification and targeted interventions in this population.
PMID- 26424216
TI - Reproducibility of compartmental subchondral bone morphometry in the mouse
tibiofemoral joint.
AB - AIM: Evidence suggests that subchondral bone can be used as a predictor for the
onset of osteoarthritis. As such, there is a need to accurately and reproducibly
quantify subchondral bone in areas where osteoarthritis develops. In this paper,
we present a novel technique for the segmentation of subchondral bone in the
tibiofemoral joint and assess the reproducibility of this method with multiple
measures and users. METHODS: The right hind leg of seven C57BL/6 mice were
excised and imaged in MUCT. The menisci and patella were manually segmented and
the image data was Gaussian filtered and binarized. An in-house algorithm was
used to generate cortical and epiphyseal volumes of interest and standard
morphometric indices for bone were computed. The intraclass correlation
coefficient (ICC), absolute precision error (PE(SD)), and precision error as a
percentage of the coefficient of variation of the repeated measurements (PE(%CV))
were calculated for each index. Additionally, an inter-user study was performed
using the same indices and statistics. RESULTS: For repeated measures, ICC ranged
from 0.869 (cortical bone volume fraction, femur) to 0.994 (degree of anisotropy,
femur). Similarly, PE(%CV) ranged from 0.84% (cortical bone volume fraction,
femur) to 5.11% (connectivity density, tibia). For repeated users, no effect was
seen in the femur with a slight effect in the tibia. CONCLUSIONS: A novel method
for the automatic segmentation of cortical and epiphyseal bone is presented and
is shown to be reproducible in C57BL/6 mice. This tool will allow for high
throughput studies of osteoarthritis in animal models.
PMID- 26424217
TI - Physiological and Behavioral Vulnerability Markers Increase Risk to Early Life
Stress in Preschool-Aged Children.
AB - The study examined whether child physiological (cortisol reactivity) and
behavioral (negative emotionality) risk factors moderate associations between the
early rearing environment, as measured by child exposure to maternal depression
and stressful life events, and preschool psychopathology and psychosocial
functioning. A sample of 156 preschool-aged children (77 boys, 79 girls; age M =
49.80 months, SD = 9.57, range: 36-71) participated in an observational
assessment of temperament and was exposed to a stress-inducing laboratory task,
during which we obtained five salivary cortisol samples. Parents completed
clinical interviews to assess child and parent psychopathology and stressful life
events. Results indicated that the combination of a blunted pattern of cortisol
reactivity and recent stressful life events was associated with higher levels of
preschoolers' externalizing symptoms and lower psychosocial functioning. In
addition, greater life stress was associated with higher levels of preschoolers'
internalizing symptoms. Lastly, children with high levels of negative
emotionality and who were exposed to maternal depression had the lowest social
competence. Our findings highlight the critical role of the early environment,
particularly for children with identified risk factors, and add to our
understanding of pathways involved in early emerging psychopathology and
impairment.
PMID- 26424218
TI - Anti-Apoptotic and Anti-Oxidant Effects of Caffeic Acid Phenethyl Ester on
Cadmium-Induced Testicular Toxicity in Rats.
AB - Cadmium (Cd) is a serious environmental and occupational contaminant and may
represent a serious health hazard to humans and other animals. Cd is reported to
induce the generation of reactive oxygen species, and induces testicular damage
in many species of animals. The goal of our study was to examine the anti
apoptotic and anti-oxidant effects of caffeic acid phenethyl ester (CAPE) on Cd
induced oxidative stress, apoptosis, and testicular injury in rats. A total of 40
male Wistar albino rats were divided into four groups: control, CAPE alone, Cd
treated, and Cd-treated with CAPE; each group consisted of 10 animals. To induce
toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and
subcutaneously injected into rats for 30 days. The rats in CAPE-treated group
were given a daily dose of 10 MUmol/kg body weight of CAPE by using
intraperitoneal injection. This application was continued daily for a total of 30
days. To date, no examinations of the anti-apoptotic and anti-oxidant properties
of CAPE on Cd-induced apoptosis, oxidative damage, and testicular injury in rat
testes have been reported. CAPE-treated animals showed an improved histological
appearance and serum testosterone levels in Cd-treated group. Our data indicate a
significant reduction in the number of apoptotic cells in testis tissues of the
Cd-treated group with CAPE treatment. Moreover, CAPE significantly suppressed
lipid peroxidation, compensated deficits in the anti-oxidant defenses in testes
tissue resulted from Cd administration. These findings suggest that the
protective potential of CAPE in Cd toxicity might be due to its anti-oxidant and
anti-apoptotic properties, which could be useful for achieving optimum effects in
Cd-induced testicular injury.
PMID- 26424219
TI - Topical trans-resveratrol ameliorates steroid-induced anterior and posterior
segment changes in rats.
AB - Steroid-induced hypertension and glaucoma is associated with increased
extracellular meshwork (ECM) deposition in trabecular meshwork (TM). Previous
studies have shown that single drop application of trans-resveratrol lowers IOP
in steroid-induced ocular hypertensive (SIOH) rats. This IOP lowering is
attributed to activation of adenosine A1 receptors, which may lead to increased
matrix metalloproteinase (MMP)-2 activity. This study evaluated the effect of
repeated topical application of trans-resveratrol for 21 days in SIOH animals on
IOP, changes in MMP-2 level in aqueous humor, trabecular meshwork and retinal
morphology and retinal redox status. We observed that treatment with trans
resveratrol results in significant and sustained IOP reduction in SIOH rats. This
IOP reduction is associated with significantly higher aqueous humor total MMP-2
level; significantly reduced TM thickness and increased number of TM cells.
Treatment with trans-resveratrol also significantly increased ganglion cell layer
(GCL) thickness, the linear cell density in the GCL and inner retina thickness;
and significantly reduced retinal oxidative stress compared to the SIOH vehicle
treated group. In conclusion, repeated dose topical application of trans
resveratrol produces sustained IOP lowering effect, which is associated with
increased level of aqueous humor MMP-2, normalization of TM and retinal
morphology and restoration of retinal redox status.
PMID- 26424220
TI - An easy, rapid method to isolate RPE cell protein from the mouse eye.
AB - The retinal pigment epithelium (RPE) is essential for maintaining the health of
the neural retina. RPE cell dysfunction plays a critical role in many common
blinding diseases including age-related macular degeneration (AMD), diabetic
retinopathy, retinal dystrophies. Mouse models of ocular disease are commonly
used to study these blinding diseases. Since isolating the RPE from the choroid
has been challenging, most techniques separate the RPE from the retina, but not
the choroid. As a result, the protein signature actually represents a
heterogeneous population of cells that may not accurately represent the RPE
response. Herein, we describe a method for separating proteins from the RPE that
is free from retinal and choroidal contamination. After removing the anterior
segment and retina from enucleated mouse eyes, protein from the RPE was extracted
separately from the choroid by incubating the posterior eyecup with a protein
lysis buffer for 10 min. Western blot analysis identified RPE65, an RPE specific
protein in the RPE lysates, but not in choroidal lysates. The RPE lysates were
devoid of rhodopsin and collagen VI, which are abundant in the retina and
choroid, respectively. This technique will be very helpful for measuring the
protein signal from the RPE without retinal or choroidal contamination.
PMID- 26424221
TI - More heads choose better than one: Group decision making can eliminate
probability matching.
AB - Probability matching is a robust and common failure to adhere to normative
predictions in sequential decision making. We show that this choice anomaly is
nearly eradicated by gathering individual decision makers into small groups and
asking the groups to decide. The group choice advantage emerged both when
participants generated responses for an entire sequence of choices without
outcome feedback (Exp. 1a) and when participants made trial-by-trial predictions
with outcome feedback after each decision (Exp. 1b). We show that the dramatic
improvement observed in group settings stands in stark contrast to a complete
lack of effective solitary deliberation. These findings suggest a crucial role of
group discussion in alleviating the impact of hasty intuitive responses in tasks
better suited to careful deliberation.
PMID- 26424222
TI - Probing the interface theory of perception: Reply to commentaries.
AB - We propose that selection favors nonveridical perceptions that are tuned to
fitness. Current textbooks assert, to the contrary, that perception is useful
because, in the normal case, it is veridical. Intuition, both lay and expert,
clearly sides with the textbooks. We thus expected that some commentators would
reject our proposal and provide counterarguments that could stimulate a
productive debate. We are pleased that several commentators did indeed rise to
the occasion and have argued against our proposal. We are also pleased that
several others found our proposal worth exploring and have offered ways to test
it, develop it, and link it more deeply to the history of ideas in the science
and philosophy of perception. To both groups of commentators: thank you. Point
and counterpoint, backed by data and theory, is the essence of science. We hope
that the exchange recorded here will advance the scientific understanding of
perception and its evolution. In what follows, we respond to the commentaries in
alphabetical order.
PMID- 26424224
TI - Diving behaviour of wildlife impacted by an oil spill: A clean-up and
rehabilitation success?
AB - The value of rehabilitating oiled wildlife is an on-going global debate. On
October 5, 2011, the cargo vessel C/V Rena grounded on Astrolabe Reef, New
Zealand (NZ), spilling over 300 tonnes of heavy fuel oil. As part of the Rena oil
spill response, 383 little blue penguins (LBP, Eudyptula minor) were captured,
cleaned, rehabilitated and released back into a cleaned environment. This
research investigates foraging behaviour changes due either to the oil spill or
by the rehabilitation process by comparing the diving behaviour of rehabilitated
(n=8) and non-rehabilitated (n=6) LBPs and with LBP populations throughout NZ.
Stabile isotope analysis of feathers was also used to investigate diet. There
were no foraging behaviour differences between rehabilitated and non
rehabilitated LBPs and the overall diving behaviour of these LBPs have similar,
if not less energetic, foraging behaviour than other LBPs in NZ. This suggests
the rehabilitation process and clean-up undertaken after the Rena appears
effective and helps justify the rehabilitation of oiled wildlife across the
world.
PMID- 26424223
TI - Volume Matters: Returning Home After Hip Fracture.
AB - OBJECTIVES: To examine the effect of the relationship between volume (number of
hip fracture admissions during the 12 months before participant's fracture) and
other facility characteristics on outcomes. DESIGN: Prospective observational
study. SETTING: U.S. skilled nursing facilities (SNFs) admitting individuals
discharged from the hospital after treatment for hip fracture between 2000 and
2007 (N = 15,439). PARTICIPANTS: Community-dwelling fee-for-service Medi-care
beneficiaries aged 75 and older admitted to U.S. hospitals for their first hip
fracture and discharged to a SNF for postacute care from 2000 to 2007 (N =
512,967). MEASUREMENTS: Successful discharge from SNF to community, defined as
returning to the community within 30 days of hospital discharge to the SNF and
remaining in the community without being institutionalized for at least 30 days,
was examined using Medicare administrative data, propensity score matching, and
instrumental variables. RESULTS: The overall rate of successful discharge to the
community was 31%. Of the 15,439 facilities, the facility interquartile range
varied from 0% (25th percentile) to 42% (75th percentile). An important
determinant of variation in discharge rate was SNF volume of hip fracture
admissions. Unadjusted successful discharge from SNF to community was 43.7% in
high-volume facilities (>24 admissions/year), versus 18.8% in low-volume
facilities (1-6 admissions/year). This facility volume effect persisted after
adjusting for participant and facility characteristics associated with outcomes
(e.g., adjusted odds ratio = 2.06, 95% confidence interval = 1.91-2.21 for volume
of 25 vs 3 admissions per year). CONCLUSION: In community-dwelling persons with
their first hip fracture, successful return to the community varies substantially
according to SNF provider volume and staffing characteristics.
PMID- 26424225
TI - The alcohol policy environment, enforcement and consumption in the United States.
AB - INTRODUCTION AND AIMS: Many studies of alcohol policies examine the presence or
absence of a single policy without considering policy strength or enforcement. We
developed measures for the strength of 18 policies (from Alcohol Policy
Information System) and levels of enforcement of those policies for the 50 US
states, and examined their associations with alcohol consumption. DESIGN AND
METHODS: We grouped policies into four domains (underage alcohol use, provision
of alcohol to underage, alcohol serving, general availability) and used latent
class analysis to assign states to one of four classes based on the configuration
of policies-weak except serving policies (6 states), average (29 states), strong
for underage use (11 states) and strong policies overall (4 states). We surveyed
1082 local enforcement agencies regarding alcohol enforcement across five
domains. We used multilevel latent class analysis to assign states to classes in
each domain and assigned each state to an overall low (15 states), moderate (19
states) or high (16 states) enforcement group. Consumption outcomes (past month,
binge and heavy) came from the Behavioral Risk Factor Surveillance System.
RESULTS: Regression models show inverse associations between alcohol consumption
and policy class, with past month alcohol consumption at 54% in the weakest
policy class and 34% in the strongest. In adjusted models, the strong underage
use policy class was consistently associated with lower consumption. Enforcement
group did not affect the policy class and consumption associations. DISCUSSION
AND CONCLUSIONS: Results suggest strong alcohol policies, particularly underage
use policies, may help to reduce alcohol consumption and related consequences.
[Erickson DJ, Lenk KM, Toomey TL, Nelson TF, Jones-Webb R. The alcohol policy
environment, enforcement, and consumption in the United States. Drug Alcohol Rev
2015;??:??-??].
PMID- 26424226
TI - Beneficial effects of fluid resuscitation via the rectum on hemodynamic disorders
and multiple organ injuries in an experimental severe acute pancreatitis model.
AB - OBJECTIVES: Exaggerated hydration is harmful for patients with severe acute
pancreatitis (SAP), and it can increase mortality rate. In this study, we
investigated the role of fluid resuscitation via the rectum (FRVR) on the
hemodynamic state and compared FRVR with intravenous fluid resuscitation (IVFR)
on resuscitation effect and organ function in an early stage of SAP. METHODS: We
studied whether FRVR corrects hemodynamic disorders at an early stage of SAP in
Spraque-Dawley (SD) rats and whether it mitigates organ dysfunction and whether
FRVR is superior to IVFR. RESULTS: In both IVFR and FRVR groups, we observed a
rebound in the mean arterial pressure (MAP) after 5 h and 6 h of administration
(p < 0.05), respectively. MAP of the FRVR group reached the same level as the
SHAM group at the end of the treatment, with hematocrit declining compared with
the non-fluid resuscitation (NFR) group (p < 0.05). A concomitant increase in
abdominal ascites and the lung wet/dry ratio by IVFR was depressed in the FRVR
group (p < 0.05). Liver function was ameliorated in both fluid resuscitation
groups (p < 0.05), consistent with histopathological improvement. TNF-alpha in
serum and MPO in the lungs and jejunum of the FRVR group were lower than the IVFR
group (p < 0.05). Pancreas histopathological injuries were ameliorated by both
IVFR and FRVR (p < 0.05). CONCLUSIONS: Our findings suggested FRVR is a potential
supplementary method for fluid management in an early stage of SAP and FRVR
should be studied further.
PMID- 26424227
TI - The Cognitive Advantages of Counting Specifically: A Representational Analysis of
Verbal Numeration Systems in Oceanic Languages.
AB - The domain of numbers provides a paradigmatic case for investigating interactions
of culture, language, and cognition: Numerical competencies are considered a core
domain of knowledge, and yet the development of specifically human abilities
presupposes cultural and linguistic input by way of counting sequences. These
sequences constitute systems with distinct structural properties, the cross
linguistic variability of which has implications for number representation and
processing. Such representational effects are scrutinized for two types of verbal
numeration systems-general and object-specific ones-that were in parallel use in
several Oceanic languages (English with its general system is included for
comparison). The analysis indicates that the object-specific systems outperform
the general systems with respect to counting and mental arithmetic, largely due
to their regular and more compact representation. What these findings reveal on
cognitive diversity, how the conjectures involved speak to more general issues in
cognitive science, and how the approach taken here might help to bridge the gap
between anthropology and other cognitive sciences is discussed in the conclusion.
PMID- 26424228
TI - Factors preventing the performance of oxygen isotope ratios as indicators of
grain yield in maize.
AB - MAIN CONCLUSION: This paper provides new insights into source-sink relationships
and transpiration processes which will eventually help to interpret delta (18) O
as a genotype selection and ecophysiological tool for maize adaptation to
drought. Oxygen isotope composition (delta(18)O) has been proposed as a
phenotyping tool to integrate leaf transpiration in C4 crops, such as maize.
Within this context we hypothesize that delta(18)O in leaves may reflect
primarily environmental and genetic variability in evaporative processes, but
that this signal may become dampened in transit from source to sink tissues. The
aim of this study was to assess the relative importance of transpirative or
translocation-related factors affecting delta(18)O in plant tissues of maize. We
performed two water regime experiments, one with two varieties under semi
controlled conditions, and another in the field with 100 genotypes during two
consecutive years. The delta(18)O in organic matter at the leaf base was strongly
correlated with the delta(18)O in stem water, indicating that it could be a good
proxy for source water in extensive samplings. Compared to leaves, we observed an
(18)O depletion in silks and grains, but not in stem-soluble organic matter. We
interpret this as evidence of exchange with unenriched water from source to sink,
but mainly occurring within sink tissues. Although grain yield (GY) and
physiological variables did not show clear intra-trial patterns against
delta(18)O, the only tissues that correlated with GY in the linear regression
approach were that of silks, giving an insight of evapotranspirative demand
during female flowering and thus of potential maize lines that are better adapted
to drought. This finding will eventually help to interpret delta(18)O as a
genotype selection and ecophysiological tool for the adaption of maize and other
crops to drought, offering insight into source-sink relationships and
transpiration processes.
PMID- 26424230
TI - Fast track to 2030: granularity at a global scale.
PMID- 26424229
TI - Protein profile of cotyledon, tegument, and embryonic axis of mature acorns from
a non-orthodox plant species: Quercus ilex.
AB - MAIN CONCLUSION: Contrary to the orthodox seeds, recalcitrant Holm oak seeds
possess the enzymatic machinery to start germination during the maturation phase.
The protein profile of the different parts, mature seeds, of the Holm oak, a non
orthodox plant species, has been characterized using one- and two-dimensional gel
electrophoresis coupled to matrix-assisted laser desorption ionization-time of
flight mass spectrometry. Protein content and profiles of the three seed tissues
(cotyledon, embryonic axis and tegument) were quite different. The embryonic axis
showed 4-fold and 20-fold higher protein content than the cotyledon and the
tegument, respectively. Two hundred and twenty-six variable proteins among the
three seed parts were identified, being classified according to their function
into eight main groups. The cotyledon presented the highest number of metabolic
and storage proteins (89% of them are legumin) compared to the embryonic axis and
tegument. The embryonic axis had the highest number of the species within the
protein fate group. The tegument presented the largest number of the defense
/stress-related and cytoskeleton proteins. This distribution is in good agreement
with the biological role of the tissues. The study of the seed tissue proteome
demonstrated a compartmentalization of pathways and a division of metabolic tasks
between embryonic axis, cotyledon and tegument. This compartmentalization
uncovered in our study should provide a starting point for understanding, at the
molecular level, the particularities of the recalcitrant seeds.
PMID- 26424231
TI - A reality check for aspirational targets to end HIV.
PMID- 26424233
TI - Unlocking adherence: is gender the key?
PMID- 26424232
TI - Partner-based adherence intervention for second-line antiretroviral therapy (ACTG
A5234): a multinational randomised trial.
AB - BACKGROUND: Adherence is key to the success of antiretroviral therapy. Enhanced
partner support might benefit patients with previous treatment failure. We aimed
to assess whether an enhanced partner-based support intervention with modified
directly observed therapy would improve outcomes with second-line therapy in HIV
infected patients for whom first-line therapy had failed. METHODS: We did a
multicentre, international, randomised clinical trial at nine sites in Botswana,
Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants
aged 18 years or older for whom first-line therapy had failed, with HIV RNA
concentrations greater than 1000 copies per mL and with a willing partner, were
randomly assigned (1:1), via computer-generated randomisation, to receive partner
based modified directly observed therapy or standard of care. Randomisation was
stratified by screening HIV RNA concentration (<=10 000 copies per mL vs >10 000
copies per mL). Participants and site investigators were not masked to group
assignment. Primary outcome was confirmed virological failure (viral load >400
copies per mL) by week 48. Analysis was by intention to treat. This trial is
registered with ClinicalTrials.gov, number NCT00608569. FINDINGS: Between April
23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the
modified directly observed therapy group (n=129) or the standard-of-care group
(n=130). 34 (26%) participants in the modified directly observed therapy group
achieved the primary endpoint of virological failure by week 48 compared with 23
(18%) participants in the standard-of-care group. The Kaplan-Meier estimated
cumulative probability of virological failure by week 48 was 25.1% (95% CI 17.7
32.4) in the modified directly observed therapy group and 17.3% (10.8-23.7) in
the standard-of-care group, for a weighted difference in standard of care versus
modified directly observed therapy of -6.6% (95% CI -16.5% to 3.2%; p=0.19). 36
(14%) participants reported at least one grade 3 or higher adverse event or
laboratory abnormality (n=21 in the modified directly observed therapy group and
n=15 in the standard-of-care group). INTERPRETATION: Partner-based training with
modified directly observed therapy had no effect on virological suppression. The
intervention does not therefore seem to be a promising strategy to increase
adherence. Intensive follow-up with clinic staff might be a viable approach in
this setting. FUNDING: AIDS Clinical Trials Group and the National Institute of
Allergy and Infectious Diseases, US National Institutes of Health.
PMID- 26424234
TI - Maximising the benefits of home-based HIV testing.
PMID- 26424235
TI - Tailoring biomedical interventions for key populations.
PMID- 26424236
TI - Postthrombolytic Antiplatelet Use for Patients with Intercerebral Hemorrhage
without Extensive Parenchymal Involvement Does Not Worsen Outcome.
AB - BACKGROUND AND PURPOSE: It is unclear whether postthrombolytic antiplatelet (AP)
therapy after thrombolytic-related hemorrhage without extensive parenchymal
involvement (THEPI) affects the clinical outcome. This study explored whether AP
administration in patients with THEPI affects short- and long-term outcomes.
METHODS: All of the data for this study were collected from the Thrombolysis
Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China)
registry. Patients with THEPI were assigned to either the AP (AP therapy should
be commenced 24 h after intravenous thrombolysis) or AP-naive groups. THEPI was
defined according to European-Australasian Acute Stroke Study II criteria. The 90
day functional outcome, 7-day National Institutes of Health Stroke Scale (NIHSS)
score, and 7-day and 90-day mortalities were compared between the AP and AP-naive
groups. Logistic regression analysis wy on the short- and long-term clinical
outcomes. RESULTS: Of the 928 patients enrolled from those in the TIMS-China
registry (n=1,440), 89 (9.6%) had nonsymptomatic intracerebral hemorrhage (ICH)
within 24-36 h after thrombolysis; 33 (37%) of these patients were given AP
therapy (AP group) and 56 (63%) were not (AP-naive group). No significant
differences were found for the risk of 7-day aggravated ICH (p=0.998), 7-day
NIHSS score (p=0.5491), 7-day mortality [odds ratio (OR)=3.427; 95% confidence
interval (95% CI)=0.344-34.160; p=0.294], 90-day mortality (OR=0.788, 95%
CI=0.154-4.040, p=0.775), or modified Rankin score 5 or 6 at 90-days (OR=1.108,
95% CI=0.249-4.928, p=0.893) between the AP and AP-naive groups after THEPI.
CONCLUSIONS: Early administration of postthrombolytic AP therapy after THEPI does
not worsen either the short- or long-term outcome. AP therapy may be a reasonable
treatment option for patients with THEPI to reduce the risk of ischemic stroke
recurrence.
PMID- 26424237
TI - Prognostic Role of Serum Levels of Uric Acid in Amyotrophic Lateral Sclerosis.
AB - BACKGROUND AND PURPOSE: It has been suggested that oxidative stress is one of the
pathomechanisms underlying amyotrophic lateral sclerosis (ALS), and thus
antioxidants such as uric acid (UA) that could reduce oxidative stress might be
beneficial in the prevention or treatment of this disease. The objective of this
study was to prospectively investigate serum UA levels in Korean ALS patients and
to relate them to disease progression. METHODS: ALS patients and healthy controls
who were individually well-matched for sex, age, and body mass index (BMI)
underwent blood testing for serum UA levels, and analyzed whether UA levels were
correlated with the disease status of the patients, as defined by the ALS
Functional Rating Scale-Revised (ALSFRS-R). RESULTS: The study included 136 ALS
patients and 136 matched controls. The UA level was lower in the ALS patients
(4.50+/-1.17 mg/dL, mean+/-SD) than in the controls (5.51+/-1.22 mg/dL; p<0.001).
Among the ALS patients, the level of UA acid was inversely correlated with the
rate of disease progression (decrease in ALSFRS-R score). Kaplan-Meier analysis
revealed that a better survival rate was more strongly correlated with top
tertile levels of serum UA than with bottom-tertile levels (log-rank test:
p=0.035). CONCLUSIONS: ALS patients had lower serum UA levels than did healthy
individuals. UA levels in ALS were negatively correlated with the rate of disease
progression and positively associated with survival, suggesting that UA levels
contribute to the progression of ALS. UA levels could be considered a biomarker
of disease progression in the early phase in ALS patients.
PMID- 26424238
TI - Comments on "Improved Serum Leptin and Ghrelin Following Bariatric Surgery
Predict better Postoperative Cognitive Function".
PMID- 26424239
TI - Acute-Onset Altitudinal Visual Field Defect Caused by Optic Canal Meningioma.
PMID- 26424240
TI - Surveillance of the System Accuracy of Two Systems for Self-Monitoring of Blood
Glucose After Market Approval.
PMID- 26424241
TI - Development of a Smartphone Application to Capture Carbohydrate, Lipid, and
Protein Contents of Daily Food: Need for Integration in Artificial Pancreas for
Patients With Type 1 Diabetes?
AB - BACKGROUND: Meal lipids (LIP) and proteins (PRO) may influence the effect of
insulin doses based on carbohydrate (CHO) counting in patients with type 1
diabetes (T1D). We developed a smartphone application for CHO, LIP, and PRO
counting in daily food and assessed its usability in real-life conditions and
potential usefulness. METHODS: Ten T1D patients used the android application for
1 week to collect their food intakes. Data included meal composition, premeal and
2-hour postmeal blood glucose, corrections for hypo- or hyperglycemia after
meals, and time for entering meals in the application. Meal insulin doses were
based on patients' CHO counting (application in blinded mode). Linear mixed
models were used to assess the statistical differences. RESULTS: In all, 187
meals were analyzed. Average computed CHO amount was 74.37 +/- 31.78 grams; LIP
amount: 20.26 +/- 14.28 grams and PRO amount: 25.68 +/- 16.68 grams. Average CHO,
LIP, and PRO contents were significantly different between breakfast and
lunch/dinner. The average time for meal entry in the application moved from 3-4
minutes to 2.5 minutes during the week. No significant impact of LIP and PRO was
found on available blood glucose values. CONCLUSION: Our study shows CHO, LIP,
and PRO intakes can be easily captured by an application on smartphone for meal
entry used by T1D patients. Although LIP and PRO meal contents did not influence
glucose levels when insulin doses were based on CHO in this pilot study, this
application could be used for further investigation of this topic, including in
closed-loop conditions.
PMID- 26424242
TI - Relationship between Plasma Albumin Concentration and Plasma Volume in 5 Inbred
Rat Strains.
AB - Using the Evans Blue procedure, we previously found strain-related differences in
plasma volumes in 5 inbred rat strains. Because albumin binds strongly with Evans
blue, this protein is important in the Evans blue method of plasma volume
determination. Therefore, we speculated that interstrain differences in plasma
albumin concentration (PAC) could distort calculated plasma volumes. To address
this concern, we used ELISA techniques to measure PAC in these inbred rat
strains. In study A, the blood volume was measured by using Evans blue dye, and
albumin was measured at the start of hemorrhage. In study B, blood volume was not
measured, and albumin was measured twice, near the start and end of hemorrhage
(approximately 14 min apart). Neither study revealed any interstrain differences
in PAC, which decreased after hemorrhage in all 5 strains. No correlation was
found between PAC and plasma volume, survival time, blood lactate, or blood base
excess. Percentage changes in PAC during hemorrhage were greater in salt
sensitive compared with Lewis rats. Moreover, these percentage changes were
associated with survival time in Fawn hooded hypertensive rats. Our data show
that the plasma volumes we measured previously were not misrepresented due to
variations in PAC.
PMID- 26424243
TI - Biochemical and Hematologic Reference Intervals for Aged Xenopus laevis in a
Research Colony.
AB - Xenopus laevis, the African clawed frog, is commonly used in developmental and
toxicology research studies. Little information is available on aged X. laevis;
however, with the complete mapping of the genome and the availability of
transgenic animal models, the number of aged animals in research colonies is
increasing. The goals of this study were to obtain biochemical and hematologic
parameters to establish reference intervals for aged X. laevis and to compare
results with those from young adult X. laevis. Blood samples were collected from
laboratory reared, female frogs (n = 52) between the ages of 10 and 14 y.
Reference intervals were generated for 30 biochemistry analytes and full
hematologic analysis; these data were compared with prior results for young X.
laevis from the same vendor. Parameters that were significantly higher in aged
compared with young frogs included calcium, calcium:phosphorus ratio, total
protein, albumin, HDL, amylase, potassium, CO2, and uric acid. Parameters found
to be significantly lower in aged frogs included glucose, AST, ALT, cholesterol,
BUN, BUN:creatinine ratio, phosphorus, triglycerides, LDL, lipase, sodium,
chloride, sodium:potassium ratio, and anion gap. Hematology data did not differ
between young and old frogs. These findings indicate that chemistry reference
intervals for young X. laevis may be inappropriate for use with aged frogs.
PMID- 26424244
TI - Microsurgical and Percutaneous Epididymal Sperm Aspiration for Sperm Collection
from Live Mice.
AB - Spermatozoa for in vitro fertilization of mouse oocytes and other methods of
assisted reproduction typically are collected from the cauda epididymis of
euthanized male mice. As an alternative to this terminal protocol, we developed
and examined 2 methods for collecting sperm from anesthetized male mice without
decreasing subsequent fertility: microsurgical epididymal sperm aspiration and,
as a refinement, percutaneous epididymal sperm aspiration. Collected sperm was
evaluated in terms of motility, concentration and in vitro fertilization ability.
After recovery, both treated and untreated control male mice underwent in vivo
fertility testing and subsequent histologic analysis of the treated male
reproductive tract (epididymis and testis). In vitro fertilization using sperm
recovered by the 2 collection methods was successfully achieved in all cases. The
in vivo fertility test and the histologic analysis revealed no impairment of
fertility and no permanent histologic alteration in the treated mice. Therefore,
we recommend both techniques as simple and effective methods for recovering high
quality epididymal mouse sperm without having to euthanize fertile male mice.
PMID- 26424245
TI - Nasal Histopathology and Intracage Ammonia Levels in Female Groups and Breeding
Mice Housed in Static Isolation Cages.
AB - Many factors influence ammonia levels in rodent cages, and high intracage ammonia
has been associated with specific types of abnormal nasal pathology in mice. The
use of autoclaved corncob bedding and the maintenance of low room humidity reduce
the accumulation of ammonia in mouse cages. However, there are no engineering
standards that define the limits of ammonia exposure for mice housed in static
isolation cages. Regulatory guidance indicates that solid bottom cages must be
sanitized at least weekly and that cage components in direct contact with animals
must be sanitized at least every 2 wk. Common practice is to replace the bottoms
and bedding of static isolation cages once weekly. To determine whether changing
static isolation cages once weekly is an appropriate performance standard for
mice, we prospectively evaluated the relationship between ammonia levels, nasal
histopathology, and housing densities in various grouping strategies of mice
housed in static isolation cages. Here, we report that the average nasal
pathology score per cage and intracage ammonia levels were correlated, but nasal
pathology scores did not differ among mice housed in breeding pairs, breeding
trios, or female groups. In light of ammonia levels and histopathology scores as
performance standards, these results suggest that a weekly cage-change frequency
for static isolation cages does not result in adverse effects. Our results
provide evidence to support current practices in the use of static isolation
cages for housing laboratory mice in modern vivaria.
PMID- 26424246
TI - Ulcerative Dermatitis in C57BL/6NCrl Mice on a Low-Fat or High-Fat Diet With or
Without a Mineralized Red-Algae Supplement.
AB - Ulcerative dermatitis (UD) is a spontaneous idiopathic disease that often affects
C57BL/6 mice or mice on a C57BL/6 background. UD is characterized by intense
pruritus and lesion formation, most commonly on the head or dorsal thorax. Self
trauma likely contributes to wound severity and delayed wound healing.
Histologically, changes are nonspecific, consisting of ulceration with
neutrophilic and mastocytic infiltration and epithelial hyperplasia and
hyperkeratosis. Diet appears to have a profound effect on the development and
progression of UD lesions. We investigated the incidence and severity of UD in
C57BL/6NCrl mice on a high-fat western-style diet (HFWD) compared with a standard
rodent chow. In addition, we examined the protective effects of dietary
supplementation with a multimineral-rich product derived from marine red algae on
UD in these 2 diet groups. HFWD-fed mice had an increased incidence of UD. In
addition, mice on a HFWD had significantly more severe clinical and histologic
lesions. Dietary mineral supplementation in mice on a HFWD decreased the
histologic severity of lesions and reduced the incidence of UD in female mice in
both diets. In conclusion, a high-fat western-style diet may potentiate UD in
C57BL/6NCrl mice. Insufficient mineral supply and mineral imbalance may
contribute to disease development. Mineral supplementation may be beneficial in
the treatment of UD.
PMID- 26424247
TI - Effect of Cage Space on Behavior and Reproduction in Crl:CD(SD) and BN/Crl
Laboratory Rats.
AB - The 2011 Guide for the Care and Use of Laboratory Animals contains
recommendations regarding the amount of cage space for mothers with litters.
Literature on cage-space use in breeding rats is sparse. We hypothesized that, if
present, differences in behavior and reproduction would be detected between the
smallest and largest cages tested. BN/Crl and Crl:CD(SD) rats were assigned to a
cage treatment (580 cm(2), 758 cm(2), 903 cm(2), or 1355 cm(2)) and breeding
configuration (single: male removed after birth of pups; pair: 1 male, 1 female)
in a factorial design for 12 wk. All cages received 20 to 25 g of nesting
material, and nests were scored weekly. Pups were weaned, sexed, and weighed
between postnatal days 18 and 26. Adult behavior and location in the cage were
videorecorded by scan-sampling on the litter's postnatal days 0 through 8 and 14
through 21. Press posture in adults and play behavior in pups were recorded
according to a 1-0 sampling method. Differences in reproductive parameters were
limited to expected differences related to rat genetic background and weaning
weight in pups, which was lowest in the pair-bred CD rats in the smallest cages.
Press posture in adults in the smaller cages increased as the pups became mobile.
Pair-housed outbred rats in the smallest commercially available cage we tested
showed behavioral changes and a lower pup weaning weight. Both laboratory animal
scientists and caging manufacturers should address the challenge of providing
more biologically relevant cage complexity rather than merely increasing floor
space.
PMID- 26424248
TI - Effects of Autoclaving Soy-Free and Soy-Containing Diets for Laboratory Rats on
Protein and Energy Values Determined In Vitro and In Vivo.
AB - Autoclaving diminishes the nutritional value of rat diets, depending on the
duration and temperature of the process and the type of dietary protein. We
evaluated in vivo and in vitro the effects of autoclaving on the protein and
energy values of soy-free and soy-containing rat diets. The true digestibility
and biological value of the dietary protein were determined in a 10-d experiment
involving 28-d-old Wistar Crl:WI(Han) male rats fed casein- or soy-containing
diet that was autoclaved for 20 min at 121 degrees C (T1), 10 min at 134
degrees C (T2), or not autoclaved (T0). The apparent protein digestibility and
metabolizable energy concentration of experimental diets were assayed during an
18-d trial involving 6-wk-old Wistar-Crl:WI(Han) male rats and compared with a
commercial diet. The neutral detergent fiber (NDF) content, amount of protein
bound to NDF, protein solubility, and in vitro ileal protein digestibility were
determined. Autoclaving decreased protein solubility, with the T2 condition
having a greater effect than that of T1, and decreased the protein parameters
determined in vivo, except for the apparent digestibility of the standard rat
diet. Autoclaving decreased metabolizable energy slightly. The Atwater formula
yielded higher values than those determined in rats, in vitro, and calculated
according to the pig equation. We conclude that autoclaving diets according to
the T1 program was less detrimental to dietary protein than was T2 and that the
NDF content and protein solubility may be helpful in assessing the effect of
autoclaving. The pig formula and in vitro method appear to be valid for
estimating the metabolizable energy of rat diets.
PMID- 26424249
TI - Severity and Distribution of Wounds in Rhesus Macaques (Macaca mulatta) Correlate
with Observed Self-Injurious Behavior.
AB - Self-injurious behavior (SIB) occurs within laboratory-housed NHP at low
frequency but can have a devastating effect on animal research and wellbeing. One
barrier to the study and clinical management of these cases is the cost of
equipment and personnel time to quantify the behavior according to the current
standard of observation and to score remotely obtained video recordings. In
studies of human SIB, in which direct observation is difficult or prohibited,
researchers have demonstrated that quantifying the tissue damage resulting from
SIB can be a useful proxy to represent the underlying behavior. We hypothesized
that the nature of wounds resulting from SIB in NHP could be used in a similar
manner to measure the abnormal behavior. Using a cohort of rhesus macaques with
high-incidence SIB, we examined severity, distribution, and number of wounds and
compared them with observed incidences of SIB during a 12-wk experiment. We found
that the number, severity, and distribution of physical wounds were associated
with the incidences of biting behavior observed during the 2 wk prior to
measurement. We also found that an increased number of wounds was associated with
increased severity. Animals with wounds of moderate severity were more likely to
also have severe wounds than were macaques with wounds that were lower than
moderate in severity. This work is the first representative study in NHP to find
that behavioral SIB correlates with physical wounding and that increases in the
frequency and number of the body regions affected correlates with the severity of
wounding.
PMID- 26424250
TI - Effect of Room Ventilation Rates in Rodent Rooms with Direct-Exhaust IVC Systems.
AB - When IVC are directly exhausted from a rodent housing room, the air quality of
the room can become independent of the intracage air quality and may reduce the
need for high room ventilation rates. This study assessed the effect of
decreasing the ventilation rate in rodent rooms using direct-exhaust IVC systems.
The study was conducted over 16 wk and compared conditions in 8 rodent rooms that
had ventilation rates of 5 to 6 air changes per hour (ACH) with those in rooms at
10 to 12 ACH. At the low ventilation rate, rooms had higher CO2 concentrations,
higher dew point temperature, and lower particulate levels and spent a greater
percentage of time above the temperature set point than did rooms at the high
rate. The levels of allergens and endotoxins in room air were the same regardless
of the ventilation rate. Differences seen in parameters within cages at the 2
ventilation rates were operationally irrelevant. We detected no total volatile
organic compounds in the room that were attributable to ammonia, regardless of
the ventilation rate. Clearing the air of ethanol after a spill took longer at
the low compared with high rate. However, ethanol clearance was faster at the low
rate when the demand-control system was activated than at the high ventilation
rate alone. Air quality in the room and in the cages were acceptable with room
ventilation rates of 5 to 6 ACH in rodent rooms that use direct-exhaust IVC
systems.
PMID- 26424251
TI - Comparison of Indoor Air Quality between 2 Ventilation Strategies in a Facility
Housing Rhesus Macaques (Macaca mulatta).
AB - Adequate indoor-air quality (IAQ)--defined by the temperature, relative humidity,
and the levels of carbon dioxide, small particles, and total volatile organic
compounds (TVOC)--is crucial in laboratory animal facilities. The ventilation
standards for controlling these parameters are not well defined. This study
assessed the effect of 2 ventilation strategies on IAQ in 2 rooms housing rhesus
macaques (Macaca mulatta). We hypothesized that using a demand-controlled
ventilation (DCV) system with a baseline ventilation rate of less than 3 fresh
air changes per hour (ACH) would maintain IAQ comparable to or better than the
traditional constant flow rate (CFR) system at 12 fresh ACH. During a 60-d study
period, each of the 2 rooms operated 30 d on DCV and 30 d on CFR ventilation. In
both rooms, temperatures remained more consistently within the established
setpoint during the DCV phase than during the CFR phase. Relative humidity did
not differ significantly between rooms or strategies. CO2 was lower during the
CFR phase than DCV phase. Small-particle and TVOC levels were lower during CFR in
the larger (3060 ft(3)) room but not the smaller (2340 ft(3)) room. During the
DCV phase, the larger room was at the baseline airflow rate over 99% of the time
and the smaller room over 96% of the time. The DCV strategy resulted in a
baseline airflow rate of less than 3 ACH, which in turn provided acceptable IAQ
over 96% of the time; higher ventilation rates were warranted only during
sanitation periods.
PMID- 26424253
TI - 3D-Printed Small-Animal Immobilizer for Use in Preclinical Radiotherapy.
AB - We have designed a method for immobilizing the subjects of small-animal studies
using a study group-specific 3D-printed immobilizer that significantly reduces
interfraction rotational variation. A cone-beam CT scan acquired from a single
specimen in a study group was used to create a 3D-printed immobilizer that can be
used for all specimens in the same study group. 3D printing allows for the
incorporation of study-specific features into the immobilizer design, including
geometries suitable for use in MR and CT scanners, holders for fiducial markers,
and anesthesia nose cones of various sizes. Using metrics of rotational setup
variations, we compared the current setup in our small-animal irradiation system,
a half-pipe bed, with the 3D-printed device. We also assessed translational
displacement within the immobilizer. The printed design significantly reduced
setup variation, with average reductions in rotational displacement of 76% +/- 3%
(1.57 to 0.37 degrees ) in pitch, 78% +/- 3% (1.85 to 0.41 degrees ) in yaw, and
87% +/- 3% (5.39 to 0.70 degrees ) in roll. Translational displacement within the
printed immobilizer was less than 1.5 +/- 0.3 mm. This method of immobilization
allows for repeatable setup when using MR or CT scans for the purpose of
radiotherapy, streamlines the workflow, and places little burden on the study
subjects.
PMID- 26424252
TI - Comparison of Heart Rate and Blood Pressure with Toe Pinch and Bispectral Index
for Monitoring the Depth of Anesthesia in Piglets.
AB - Determining depth of anesthesia (DOA) is a clinical challenge in veterinary
medicine, yet it is critical for the appropriate oversight of animals involved in
potentially painful experimental procedures. Here, we investigated various
parameters used to monitor conscious awareness during surgical procedures and
refined the application of noxious stimuli to anesthetized animals. Specifically
we used a common stimulus, a compressive toe pinch (TP), to determine physiologic
changes that accompanied a positive or negative motion response in isoflurane
anesthetized piglets. A positive response was defined as any reflexive
withdrawal, whereas a negative response was defined as the absence of motion
after stimulation. We also assessed the utility of the bispectral index (BIS) for
its ability to predict a motion response to TP. The average of BIS values over 1
min (BISmean) was recorded before and after TP. In piglets with a positive
response to TP, heart rate (HR), but not blood pressure (BP), increased
significantly, but receiver operating characteristic (ROC) analysis revealed that
HR was not a sensitive, specific predictor of TP motion response. Both before and
after TP, BISmean was a strong predictor of a positive motion response. We
conclude that HR and noninvasive BP changes are not clinically reliable
indicators of anesthetic depth when assessed immediately after a peripherally
applied compressive force as an indicator stimulus; however, BISmean and response
TP are acceptable for assessing DOA in piglets maintained under isoflurane
anesthesia.
PMID- 26424254
TI - Voluntary Oral Administration of Losartan in Rats.
AB - Gavage is a widely performed technique for daily dosing in laboratory rodents.
Although effective, gavage comprises a sequence of potentially stressful
procedures for laboratory animals that may introduce bias into experimental
results, especially when the drugs to be tested interfere with stress-dependent
parameters. We aimed to test vehicles suitable for drug delivery by voluntary
ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to
test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for
long-term voluntary oral administration of losartan, an angiotensin II receptor
blocker. Vehicles were administered for 28 d without drug to assess effects on
the glucose level and serum lipid profile. Losartan was mixed with vehicles and
either offered to the rats or administered by gavage (14 d) for subsequent
quantification of losartan plasma levels by HPLC. After a 2-d acclimation period,
all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT
administration reduced blood glucose levels. The SUG group had higher
concentrations of losartan than did the gavage group, without changes in lipid
and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for
daily single-dose voluntary ingestion of losartan and that SUG was the best
alternative overall. Drug bioavailability was not reduced after voluntary
ingestion, suggesting that this method is highly effective for chronic oral
administration of losartan to laboratory rodents.
PMID- 26424255
TI - Pharmacokinetics of Ceftiofur Crystalline Free Acid in Male Rhesus Macaques
(Macaca mulatta) after Subcutaneous Administration.
AB - Trauma is a common sequela to agonistic social encounters in rhesus macaques
(Macaca mulatta), and veterinarians often prescribe antibiotics as part of a
balanced treatment plan. Long-acting, single-dose, injectable antibiotics for use
in rhesus macaques are unavailable currently. Ceftiofur crystalline free acid
(CCFA) is a long-acting, single-dose, injectable third-generation cephalosporin
that provides at least 7 d of ceftiofur therapeutic plasma concentrations in
swine (Sus scrofa domesticus). We hypothesized that CCFA would achieve similar
therapeutic concentrations (>= 0.2 MUg/mL) in rhesus macaques. We describe the
pharmacokinetic profile of CCFA in healthy, adult male rhesus macaques ( n = 6)
in this 2-period, 2-treatment crossover study of 5 and 20 mg/kg SC administered
once. Plasma ceftiofur metabolite concentrations were determined prior to and for
a maximum of 21 d after administration. Noncompartmental pharmacokinetic analysis
was performed. The 5-mg dose achieved a maximal plasma concentration of 2.24 +/-
0.525 MUg/mL at 2.59 +/- 1.63 h, an AUC of 46.9 +/- 17.6 h/MUg/mL, and a terminal
elimination half-life of 56.5 +/- 21.7 h; for the 20-mg/kg dose, these parameters
were 9.18 +/- 4.90 MUg/mL at 1.82 +/- 1.30 h, 331 +/- 84.4 h/MUg/mL, and 69.7 +/-
8.86 h, respectively. No adverse effects were noted after either dose. Macaques
maintained plasma ceftiofur concentrations of 0.2 MUg/mL or greater for at least
2 d after 5 mg/kg SC and at least 7 d after 20 mg/kg SC.
PMID- 26424256
TI - Effects of Clove Oil as a Euthanasia Agent on Blood Collection Efficiency and
Serum Cortisol Levels in Danio rerio.
AB - Zebrafish are an important laboratory animal model for biomedical research and
are increasingly being used for behavioral neuroscience. Tricaine
methanesulfonate (MS222) is the standard agent used for euthanasia of zebrafish.
However, recent studies of zebrafish behavior suggest that MS222 may be aversive,
and clove oil might be a possible alternative. In this study, we compared the
effects of MS222 or clove oil as a euthanasia agent in zebrafish on the volume of
blood collected and on serum levels of cortisol. Greater amounts of serum could
be collected and lower serum levels of cortisol were present in fish euthanized
with clove oil compared with equipotent dose of MS222. Euthanasia with clove oil
did not blunt the expected elevation of serum cortisol levels elicited by an
acute premortem stress. According to our findings, clove oil is a fast-acting
agent that minimizes the cortisol response to euthanasia in zebrafish and allows
the collection of large volumes of blood postmortem. These results represent a
significant refinement in euthanasia methods for zebrafish.
PMID- 26424257
TI - Peptide Antibodies: Past, Present, and Future.
AB - Peptide antibodies recognize epitopes with amino acid residues adjacent in
sequence ("linear" epitopes). Such antibodies can be made to virtually any
sequence and have been immensely important in all areas of molecular biology and
diagnostics due to their versatility and to the rapid growth in protein sequence
information. Today, peptide antibodies can be routinely and rapidly made to large
numbers of peptides, including peptides with posttranslationally modified
residues, and are used for immunoblotting, immunocytochemistry,
immunohistochemistry, and immunoassays. In the future, peptide antibodies will
continue to be immensely important for molecular biology, TCR- and MHC-like
peptide antibodies may be produced routinely, peptide antibodies with
predetermined conformational specificities may be designed, and peptide-based
vaccines may become part of vaccination programs.
PMID- 26424258
TI - The Structure of Natural and Recombinant Antibodies.
AB - Immunoglobulins (Ig) isotypes A, D, E, G, and M are glycoproteins which are
mainly composed of a "Y"-shaped Ig monomer (~150 kDa), consisting of two light
and two heavy chains. Both light and heavy chains contain variable (N-terminal)
and constant regions (C-terminal). Each light chain consists of one variable
domain and one constant domain, whereas each heavy chain has one variable domain
and three constant domains. However, heavy-chain antibodies consisting of only
heavy chains and lacking the light chains are found in camelids and cartilaginous
fishes. Unlike other immunoglobulins, the heavy chain of avian antibody IgY (~180
kDa) consists of four constant domains. The single-chain variable fragment (scFv;
~25 kDa) of an antibody contains variable regions of antibody heavy and light
chains. The fragment antigen-binding (Fab; ~50 kDa) region has the full antibody
light chain but the heavy chain is composed of a variable region and one constant
domain.
PMID- 26424259
TI - Prediction of Antigenic B and T Cell Epitopes via Energy Decomposition Analysis:
Description of the Web-Based Prediction Tool BEPPE.
AB - Unraveling the molecular basis of immune recognition still represents a
challenging task for current biological sciences, both in terms of theoretical
knowledge and practical implications. Here, we describe the physical-chemistry
methods and computational protocols for the prediction of antibody-binding
epitopes and MHC-II loaded epitopes, starting from the atomic coordinates of
antigenic proteins (PDB file). These concepts are the base of the Web tool BEPPE
(Binding Epitope Prediction from Protein Energetics), a free service that returns
a list of putative epitope sequences and related blast searches against the
Uniprot human complete proteome. BEPPE can be employed for the study of the
biophysical processes at the basis of the immune recognition, as well as for
immunological purposes such as the rational design of biomarkers and targets for
diagnostics, therapeutics, and vaccine discovery.
PMID- 26424260
TI - Prediction of Antibody Epitopes.
AB - Antibodies recognize their cognate antigens in a precise and effective way. In
order to do so, they target regions of the antigenic molecules that have specific
features such as large exposed areas, presence of charged or polar atoms,
specific secondary structure elements, and lack of similarity to self-proteins.
Given the sequence or the structure of a protein of interest, several methods
exploit such features to predict the residues that are more likely to be
recognized by an immunoglobulin. Here, we present two methods (BepiPred and
DiscoTope) to predict linear and discontinuous antibody epitopes from the
sequence and/or the three-dimensional structure of a target protein.
PMID- 26424261
TI - Fmoc Solid-Phase Peptide Synthesis.
AB - Synthetic peptides are important as drugs and in research. Currently, the method
of choice for producing these compounds is solid-phase peptide synthesis. In this
nonspecialist review, we describe the scope and limitations of Fmoc solid-phase
peptide synthesis. Furthermore, we provide a detailed protocol for Fmoc peptide
synthesis.
PMID- 26424262
TI - Peptide-Carrier Conjugation.
AB - To produce antibodies against synthetic peptides it is necessary to couple them
to a protein carrier. This chapter provides a nonspecialist overview of peptide
carrier conjugation. Furthermore, a protocol for coupling cysteine-containing
peptides to bovine serum albumin is outlined.
PMID- 26424263
TI - Solid-Phase Peptide-Carrier Conjugation.
AB - Conjugation to carrier proteins is necessary for peptides to be able to induce
antibody formation when injected into animals together with a suitable adjuvant.
This is usually performed by conjugation in solution followed by mixing with the
adjuvant. Alternatively, the carrier may be adsorbed onto a solid support
followed by activation and conjugation with the peptide by solid-phase chemistry.
Different reagents can be used for conjugation through peptide functional groups
(-SH, -NH2, -COOH) and various carrier proteins may be used depending on the
peptides and the intended use of the antibodies. The solid phase may be an ion
exchange matrix, from which the conjugate can subsequently be eluted and mixed
with adjuvant. Alternatively, the adjuvant aluminum hydroxide may be used as the
solid-phase matrix, whereupon the carrier is immobilized and conjugated with
peptide. The resulting adjuvant-carrier-peptide complexes may then be used
directly for immunization.
PMID- 26424264
TI - Analysis of Peptides and Conjugates by Amino Acid Analysis.
AB - Amino acid analysis is a highly accurate method for characterization of the
composition of synthetic peptides. Together with mass spectrometry, it gives a
reliable control of peptide quality and quantity before conjugation and
immunization. Peptides are hydrolyzed, preferably in gas phase, with 6 M HCl at
110 degrees C for 20-24 h and the resulting amino acids analyzed by ion-exchange
chromatography with post-column ninhydrin derivatization. Depending on the
hydrolysis conditions, tryptophan is destroyed, and cysteine also, unless
derivatized, and the amides, glutamine and asparagine, are deamidated to glutamic
acid and aspartic acid, respectively. Three different ways of calculating results
are suggested, and taking the above limitations into account, a quantitation
better than 5% can usually be obtained.
PMID- 26424265
TI - Characterization of Synthetic Peptides by Mass Spectrometry.
AB - Mass spectrometry (MS) is well suited for analysis of the identity and purity of
synthetic peptides. The sequence of a synthetic peptide is most often known, so
the analysis is mainly used to confirm the identity and purity of the peptide.
Here, simple procedures are described for MALDI-TOF-MS and LC-MS of synthetic
peptides.
PMID- 26424266
TI - Interpretation of Tandem Mass Spectrometry (MSMS) Spectra for Peptide Analysis.
AB - The aim of this chapter is to give a short introduction to peptide analysis by
mass spectrometry (MS) and interpretation of fragment mass spectra. Through
examples and guidelines we demonstrate how to understand and validate search
results and how to perform de novo sequencing based on the often very complex
fragmentation pattern obtained by tandem mass spectrometry (also referred to as
MSMS). The focus is on simple rules for interpretation of MSMS spectra of tryptic
as well as non-tryptic peptides.
PMID- 26424267
TI - Polyclonal Peptide Antisera.
AB - Polyclonal antibodies are relatively easy to produce and may supplement
monoclonal antibodies for some applications or even have some advantages. The
choice of species for production of (peptide) antisera is based on practical
considerations, including availability of immunogen (vaccine) and animals. Two
major factors govern the production of antisera: the nature of adaptive immune
responses, which take place over days/weeks and ethical guidelines for animal
welfare. Here, simple procedures for immunization of mice, rabbits, sheep, goats,
pigs, horses, and chickens are presented.
PMID- 26424268
TI - Production and Screening of Monoclonal Peptide Antibodies.
AB - Hybridoma technology is a remarkable and indispensable tool for generating high
quality monoclonal antibodies. Hybridoma-derived monoclonal antibodies not only
serve as powerful research and diagnostic reagents, but have also emerged as the
most rapidly expanding class of therapeutic biologicals. In this chapter, an
overview of hybridoma technology and the laboratory procedures used routinely for
hybridoma production and antibody screening are presented, including
characterization of peptide antibodies.
PMID- 26424269
TI - Production of Epitope-Specific Antibodies by Immunization with Synthetic Epitope
Peptide Formulated with CpG-DNA-Liposome Complex Without Carriers.
AB - Antibody production using synthetic peptides has been investigated extensively to
develop therapeutic antibodies and prophylactic vaccines. Previously, we reported
that a complex of CpG-DNA and synthetic peptides corresponding to B cell
epitopes, encapsulated in a phosphatidyl-beta-oleoyl-gamma-palmitoyl ethanolamine
(DOPE):cholesterol hemisuccinate (CHEMS) complex, significantly enhanced the
synthetic peptide-specific IgG production. Here, we describe synthetic peptide
based epitope screening and antibody production without conventional carriers.
PMID- 26424270
TI - Thioredoxin-Displayed Multipeptide Immunogens.
AB - Fusion to carrier proteins is an effective strategy for stabilizing and providing
immunogenicity to peptide epitopes. This is commonly achieved by cross-linking of
chemically synthesized peptides to carrier proteins. An alternative approach is
internal grafting of selected peptide epitopes to a scaffold protein via double
stranded-oligonucleotide insertion or gene synthesis, followed by recombinant
expression of the resulting chimeric polypeptide. The scaffold protein should
confer immunogenicity to the stabilized and structurally constrained peptide, but
also afford easy production of the antigen in recombinant form. A macromolecular
scaffold that meets the above criteria is the redox protein thioredoxin,
especially bacterial thioredoxin. Here we describe our current methodology for
internal grafting of selected peptide epitopes to thioredoxin as tandemly
arranged multipeptide repeats ("Thioredoxin Displayed Multipeptide Immunogens"),
bacterial expression and purification of the recombinant thioredoxin-multipeptide
fusion proteins and their use as antigens for the production of anti-peptide
antibodies for prophylactic vaccine as well as diagnostic purposes.
PMID- 26424271
TI - The Purification of Natural and Recombinant Peptide Antibodies by Affinity
Chromatographic Strategies.
AB - The purification of peptide antibodies (e.g., IgG, IgY, scFv, and Fab) are
described in this chapter. Affinity chromatographic purification, a very
convenient and effective antibody purification strategy, is used to isolate
peptide antibodies based on specific binding, i.e., binding of the antibody to a
column on which its specific ligand is immobilized with subsequent elution of the
purified antibody. In addition, the application of purification methods based on
the use of proteins A, G, and L, each of which bind to specific domains on an
antibody/fragment, or the use of specific tags (e.g., histidine and biotin)
attached to antibodies or antigens are also described.
PMID- 26424272
TI - Isolation of Camelid Single-Domain Antibodies Against Native Proteins Using
Recombinant Multivalent Peptide Ligands.
AB - Generation of antibodies against desired epitopes on folded proteins may be
hampered by various characteristics of the target protein, including antigenic
and immunogenic dominance of irrelevant epitopes and/or steric occlusion of the
desired epitope. In such cases, peptides encompassing linear epitopes of the
native protein represent attractive alternative reagents for immunization and
screening. Peptide antigens are typically prepared by fusing or conjugating the
peptide of interest to a carrier protein. The utility of such antigens depends on
many factors including the peptide's amino acid sequence, display valency,
display format (synthetic conjugate vs. recombinant fusion) and characteristics
of the carrier. Here we provide detailed protocols for: (1) preparation of DNA
constructs encoding peptides fused to verotoxin (VT) multimerization domain; (2)
expression, purification, and characterization of the multivalent peptide-VT
ligands; (3) concurrent panning of a non-immune phage-displayed camelid VHH
library against the peptide-VT ligands and native protein; and (4) identification
of VHHs enriched via panning using next-generation sequencing techniques. These
methods are simple, rapid and can be easily adapted to yield custom peptide-VT
ligands that appear to maintain the antigenic structures of the peptide. However,
we caution that peptide sequences should be chosen with great care, taking into
account structural, immunological, and biophysical information on the protein of
interest.
PMID- 26424274
TI - Structural Characterization of Peptide Antibodies.
AB - The role of proteins as very effective immunogens for the generation of
antibodies is indisputable. Nevertheless, cases in which protein usage for
antibody production is not feasible or convenient compelled the creation of a
powerful alternative consisting of synthetic peptides. Synthetic peptides can be
modified to obtain desired properties or conformation, tagged for purification,
isotopically labeled for protein quantitation or conjugated to immunogens for
antibody production. The antibodies that bind to these peptides represent an
invaluable tool for biological research and discovery. To better understand the
underlying mechanisms of antibody-antigen interaction here we present a pipeline
developed by us to structurally classify immunoglobulin antigen binding sites and
to infer key sequence residues and other variables that have a prominent role in
each structural class.
PMID- 26424273
TI - Generation of TCR-Like Antibodies Using Phage Display.
AB - The adaptive immune response against cancer consists of two arms: the humoral
response from B cells, and the cell-mediated response from T cells. The humoral
response has the advantage of diversity, theoretically recognizing antigens of
any type (sugar, protein, lipid, etc.), but is generally limited to surface
expressed targets. T cells on the other hand, can recognize intracellular
targets, but only if they are proteins, and presented as small peptide fragments
on major histocompatibility complex (MHC) cell surface antigens. However, with
advances in protein engineering and phage display, it has become feasible to
quickly identify and generate antibodies or single-chain variable fragments
against peptide-MHC, thus bridging the two arms, and allowing for recognition,
identification, and effector responses against cells expressing intracellular
targets.
PMID- 26424275
TI - Automated High-Throughput Mapping of Linear B-Cell Epitopes Using a Statistical
Analysis of High-Density Peptide Microarray Data.
AB - Detailed information of antibodies' specificity is often missing or inadequate
even for continuous (i.e., linear) epitopes. Recent developments in peptide
microarray technology has enabled the synthesis of up to two million peptides per
array thereby allowing linear peptide epitopes to be examined by a systematic
amino acid substitution and positional scanning approach. This kind of analysis
generates a very large body of data, which needs to be analyzed and interpreted
in a robust and automated manner. Here, we describe a rational systematic
approach to define linear antibody epitopes using ANOVA statistics to identify
not only significant but also important residues involved in antibody
recognition. This statistical approach can be used to perform a comprehensive
linear epitope discovery. For polyclonal antibodies, this could be extended to
entire proteins pinpointing critical residues for each epitope. We argue that the
ANOVA analysis levels out issues of unknown peptide concentration/quality and
unknown antibody titers leading to identification of epitopes that otherwise
would be neglected if the evaluation was based merely on signal strength.
PMID- 26424276
TI - Characterization of Peptide Antibodies by Epitope Mapping Using Resin-Bound and
Soluble Peptides.
AB - Characterization of peptide antibodies through identification of their target
epitopes is of utmost importance. Understanding antibody specificity at the amino
acid level provides the key to understand the specific interaction between
antibodies and their epitopes and their use as research and diagnostic tools as
well as therapeutic agents. This chapter describes a straightforward strategy for
mapping of continuous peptide antibody epitopes using resin-bound and soluble
peptides. The approach combines three different types of peptide sets for full
characterization of peptide antibodies: (1) overlapping peptides, used to locate
antigenic regions; (2) truncated peptides, used to identify the minimal peptide
length required for antibody binding; and (3) substituted peptides, used to
identify the key residues important for antibody binding and to determine the
specific contribution of key residues. For initial screening resin-bound peptides
are used for epitope estimation, while soluble peptides subsequently are used for
fine mapping. The combination of resin-bound peptides and soluble peptides for
epitope mapping provides a time-sparing and straightforward approach for
characterization of peptide antibodies.
PMID- 26424277
TI - Screening and Characterization of Linear B-Cell Epitopes by Biotinylated Peptide
Libraries.
AB - Identification of B-cell epitopes is important for the use of antibodies as
therapeutic agents, the design of epitope-based vaccines against infectious
diseases, and immunological assays based on peptide antibodies. A large number of
methods are available for epitope mapping, but many of them require specialized
laboratories and are expensive. In this chapter, we describe a high-throughput
approach for epitope mapping of peptide antibodies by use of a library of
soluble, overlapping, biotinylated peptides. As example, we present
characterization of monoclonal and polyclonal antibodies specific for peptides of
Mycobacterium tuberculosis acyl carrier protein AcpM and the Chlamydia
trachomatis chaperone Ct043 by ELISA.
PMID- 26424278
TI - Bead-Based Peptide Arrays for Profiling the Specificity of Modification State
Specific Antibodies.
AB - Modification state-specific antibodies are powerful tools for investigating
posttranslational modifications in proteins. The majority of these antibodies
have been generated against peptide-antigen conjugates. They are useful in a
plethora of methods, such as Western blotting, immunohistochemistry, sandwich
immunoassay, immunoprecipitation, and immunoprecipitation coupled with mass
spectrometry. Phosphorylation, acetylation, methylation, sulfation,
nitrosylation, ubiquitination, and sumoylation are some of the modifications that
can be studied using such antibodies. However, investigating the on- and off
target binding of antibodies is crucial to the interpretation of experimental
data. Peptide arrays are excellent tools for such in-depth studies of off-target
and on-target binding of antibodies. Dozens or even hundreds of modified peptides
can be integrated into a single experimental setup to analyze the antibody's
binding behavior. Here, we propose three different protocols for peptide bead
array generation and describe their suitability for such types of assay.
PMID- 26424279
TI - Surface Plasmon Resonance Method to Evaluate Anti-citrullinated Protein/Peptide
Antibody Affinity to Citrullinated Peptides.
AB - Surface plasmon resonance (SPR) technique is extremely interesting in immunology
because it has the potential to directly visualize biomolecular interactions in
real-time monitoring antibody affinity, one of the parameters affecting
pathogenicity in autoimmune diseases. Herein we describe the affinity evaluation
of anti-citrullinated peptide antibodies (ACPA) to a peptide-based biosensor by
SPR. The method describes the purification of ACPA isolated from rheumatoid
arthritis (RA) patients using affinity columns, the strategy employed for the
immobilization of citrullinated peptides onto a sensor chip, and the evaluation
of the specific binding of purified ACPA to immobilized peptides.
PMID- 26424280
TI - Specificity Analysis of Histone Modification-Specific Antibodies or Reading
Domains on Histone Peptide Arrays.
AB - Histone posttranslational modifications (PTMs) have a crucial role in chromatin
regulation and dynamics. They are specifically bound by so-called reading
domains, which mediate the biological effects of histone PTMs. On a similar note,
antibodies are invaluable reagents in chromatin biology for the detection,
characterization, and mapping of histone PTMs. Despite these central roles in
chromatin research and biology, the specificity of many antibodies and reading
domains has been insufficiently characterized and documented. Here we describe in
detail the application of the MODifiedTM Histone Peptide Array for the
investigation of the binding specificity of histone binding antibodies or
domains. The array contains 384 histone tail peptides carrying 59
posttranslational modifications in different combinations which can be used to
study the primary binding specificity, but at the same time also allow to
determine the combinatorial effect of secondary marks on antibody or reading
domain binding.
PMID- 26424281
TI - Prion-Specific Antibodies Produced in Wild-Type Mice.
AB - Peptide-specific antibodies produced against synthetic peptides are of high value
in probing protein structure and function, especially when working with
challenging proteins, including not readily available, non-immunogenic, toxic,
and/or pathogenic proteins. Here, we present a straightforward method for
production of mouse monoclonal antibodies (MAbs) against peptides representing
two sites of interest in the bovine prion protein (boPrP), the causative agent of
bovine spongiform encephalopathy ("mad cow disease") and new variant Creutzfeldt
Jakob's disease (CJD) in humans, as well as a thorough characterization of their
reactivity with a range of normal and pathogenic (misfolded) prion proteins. It
is demonstrated that immunization of wild-type mice with ovalbumin-conjugated
peptides formulated with Freund's adjuvant induces a good immune response,
including high levels of specific anti-peptide antibodies, even against peptides
very homologous to murine protein sequences. In general, using the strategies
described here for selecting, synthesizing, and conjugating peptides and
immunizing 4-5 mice with 2-3 different peptides, high-titered antibodies reacting
with the target protein are routinely obtained with at least one of the peptides
after three to four immunizations with incomplete Freund's adjuvant.
PMID- 26424282
TI - Immunoblotting with Peptide Antibodies: Differential Immunoreactivities Caused by
Certain Amino Acid Substitutions in a Short Peptide and Possible Effects of
Differential Refolding of the Peptide on a Nitrocellulose or PVDF Membrane.
AB - Immunodetection using antibodies, e.g., Western blotting, is generally utilized
to measure the amount of a certain protein in a protein mixture. For valid
interpretation of results observed by immunodetection, strict attention must be
paid to the factors affecting the immunoreactivities of the antibodies. We here
describe the step-by-step procedures to demonstrate that substitution of certain
amino acids in a peptide can cause remarkable differences in its immunoreactivity
with antibodies against epitope tags in the immobilized peptide. Refolding of the
peptide on the membrane in a way that masks the epitope to different degrees was
the possible reason for their distinct immunoreactivities with the antibodies.
The results in this chapter suggest that we need to interpret carefully the
experimental results involving immunodetection.
PMID- 26424283
TI - Immunocytochemical and Immunohistochemical Staining with Peptide Antibodies.
AB - Peptide antibodies are particularly useful for immunocytochemistry (ICC) and
immunohistochemistry (IHC), where antigens may denature due to fixation of
tissues and cells. Peptide antibodies can be made to any defined sequence,
including unknown putative proteins and posttranslationally modified sequences.
Moreover, the availability of large amounts of the antigen (peptide) allows
inhibition/adsorption controls, which are important in ICC/IHC, due to the many
possibilities for false-positive reactions caused by immunoglobulin Fc receptors,
nonspecific reactions, and cross-reactivity of primary and secondary antibodies
with other antigens and endogenous immunoglobulins, respectively. Here, simple
protocols for ICC and IHC are described together with recommendations for
appropriate controls.
PMID- 26424284
TI - Designing B-Cell Epitopes for Immunotherapy and Subunit Vaccines.
AB - Rationally designed subunit vaccines mainly consist of small peptides or B-cell
epitopes, which can stimulate the body's immune response. Development of subunit
vaccines is a very tedious and costly process. One of the imperative and crucial
steps of vaccine development is the identification of highly competent B-cell
epitopes as most of the proteins and fragments of proteins are immunologically
irrelevant. With the advances in bioinformatics tools, it can be possible to
precisely narrow down potential B-cell epitopes from the whole proteome of any
pathogen. This chapter sheds light on prediction and designing of B-cell epitopes
using two in silico tools LBtope and IgPred.
PMID- 26424285
TI - Enterovirus-Specific Anti-peptide Antibodies.
AB - Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth
disease (HFMD) which is generally regarded as a mild childhood disease. In recent
years, EV71 has emerged as a significant pathogen capable of causing high
mortalities and severe neurological complications in large outbreaks in Asia. A
formalin-inactivated EV71 whole virus vaccine has completed phase III trial in
China but is currently unavailable clinically. The high cost of manufacturing and
supply problems may limit practical implementations in developing countries.
Synthetic peptides representing the native primary structure of the viral
immunogen which is able to elicit neutralizing antibodies can be made readily and
is cost effective. However, it is necessary to conjugate short synthetic peptides
to carrier proteins to enhance their immunogenicity. This review describes the
production of cross-neutralizing anti-peptide antibodies in response to
immunization with synthetic peptides selected from in silico analysis, generation
of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from
Poliovirus, and evaluation of the neutralizing activities of the anti-peptide
antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were
cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and
ECHO13.
PMID- 26424286
TI - Therapeutic HIV Peptide Vaccine.
AB - Therapeutic vaccines aim to control chronic HIV infection and eliminate the need
for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being
pursued as part of a functional cure for HIV/AIDS. We have outlined a basic
protocol for inducing new T cell immunity during chronic HIV-1 infection directed
to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes.
The rationale for selecting HIV peptides and adjuvants are provided. Peptide
subunit vaccines are regarded as safe due to the simplicity, quality, purity, and
low toxicity. The caveat is reduced immunogenicity and hence adjuvants are
included to enhance and direct the immune response. Although the vaccine has been
tested in ART naive individuals, we recommend future testing of the vaccine
during (early started) ART that improves immune function and to select
individuals likely to benefit. Peptides representing other epitopes may be used.
PMID- 26424287
TI - Protein biomarkers and microbial profiles in peri-implantitis.
AB - OBJECTIVES: The aim of the present investigation was to determine the profile of
peri-implant crevicular fluid (PICF) biomarkers combined with microbial profiles
from implants with healthy peri-implant tissues and peri-implantitis to assess
real-time disease activity. MATERIAL AND METHODS: Sixty-eight patients were
included in this cross-sectional study. They were divided into two groups: 34
patients with at least one healthy implant (control) and 34 with at least one
peri-implantitis affected implant (test). Total DNA content and qPCR analysis for
periodontal bacteria obtained from subgingival plaque samples (Aggregatibacter
actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis,
Tannerella forsythia, and Treponema denticola) and a PICF analysis for IL-1beta,
VEGF, MMP-8, TIMP-2, and OPG were performed. The individual and combined
diagnostic ability of each biomarker for peri-implantitis and target bacterial
species were analyzed. RESULTS: The mean concentration of IL-1beta (44.6 vs.
135.8 pg/ml; P < 0.001), TIMP-2 (5488.3 vs. 9771.8 pg/ml; P = 0.001), VEGF (59.1
vs. 129.0 pg/ml; P = 0.012), and OPG (66.5 vs. 111.7 pg/ml; P = 0.050) was
increased in the peri-implantitis patients. The mean expression of MMP-8 (6029.2
vs. 5943.1 pg/ml; P = 0.454) and did not reveal a meaningful difference among
groups. Total bacterial DNA of selected microorganisms was associated with a
threefold or greater increase in peri-implantitis although no statistical
significant difference. The ability to diagnose diseased sites was enhanced by T.
denticola combined with IL-1beta, VEGF, and TIMP-2 PICF levels. CONCLUSION: The
present data suggest that the increased levels of the selected PICF-derived
biomarkers of periodontal tissue inflammation, matrix degradation/regulation, and
alveolar bone turnover/resorption combined with site-specific microbial profiles
may be associated with peri-implantitis and could have potential as predictors of
peri-implant diseases.
PMID- 26424288
TI - Betauried bumper syndrome presenting with hematemesis two weeks after
percutaneous endoscopic gastrostomy placement.
PMID- 26424289
TI - Vulval symptoms after the menopause - Not all atrophy!
AB - Vulval and vaginal symptoms are common after the menopause and are frequently
assumed to be due to the normal physiological changes that occur at this time.
However, there are several important dermatoses that can occur in this patient
group which need accurate diagnosis and appropriate management. This review
discusses the clinical features and basic management of some of the common vulval
problems occurring after the menopause.
PMID- 26424290
TI - Effect of Qiguiyin Decoction on multidrug-resistant Pseudomonas aeruginosa
infection in rats.
AB - OBJECTIVE: To investigate the effect of Qiguiyin Decoction, QGYD) on multidrug
resistant Pseudomonas aeruginosa infection in Sprague-Dawley (SD) rats. METHODS:
A pseudomonal infection model in SD rats was established by injecting multidrug
resistant P. aeruginosa intraperitoneally. Infected rats were randomized into
four groups treated with Pure water, QGYD, ceftazidime, or combined QGYD and
ceftazidime. Blood samples were obtained from the abdominal aorta. Serum was then
collected and analyzed by peptide array for immune responsiveness to multidrug
resistant beta-lactamase proteins, including Verona integronen-coded metallo-beta
lactamase 1 (VIM-1), Sao Paulo metallo-beta-lactamase 1 (SPM-1), and Temoniera
(TEMs). Blood levels of interleukin-1beta (IL-1beta), interleukin-4 (IL-4), and
interferon-gamma (IFN-gamma) were assessed by enzyme-linked immunosorbent assay.
RESULTS: QGYD enhanced antibody reactivity against VIM-1 [epitopes 7-11 and 36
40] and TEM-1 [epitopes 26-27, 52-55, and 66-70]. QGYD treatment restored the
compromised antibody reactivity against VIM-1 [epitopes 53-54 and 56-58] and SPM
1 [epitopes 16-19 and 82-85] following pseudomonal infection. Serum levels of IL
1beta and Th1/Th2 in the rats were significantly elevated following pseudomonal
infection (P<0.05 orP<0.01). In contrast, QGYD and combination QGYD and
ceftazidime treatment restored the elevated serum IL-1beta and Th1/Th2 levels to
normal (P>0.05). CONCLUSIONS: QGYD improves the immune response to pseudomonal
infection in rats by stimulating the production of protective antibodies against
drug-resistant proteins VIM-1, SPM-1, and TEM-1. In addition, it protects the
immune system and maintains immune responsiveness by restoring IL-1beta and
Th1/Th2 levels.
PMID- 26424291
TI - Effect of ligustrazine nanoparticles nano spray on transforming growth factor
beta/Smad signal pathway of rat peritoneal mesothelial cells induced by tumor
necrosis factor-alpha.
AB - OBJECTIVE: To study the effect of ligustrazine nanoparticles nano spray (LNNS) on
transforming growth factor beta (TGF-beta)/Smad signal protein of rat peritoneal
mesothelial cells (RPMC) induced by tumor necrosis factor alpha (TNF-alpha), and
the anti-adhesion mechanism of LNNS in the abdominal cavity. METHODS: The primary
culture and subculture of rat peritoneal mesothelial cells (RPMC) was processed
by trypsin digestion method in vitro. The third generation was identifified for
experiment and divided into 5 groups: a blank group: RPMC without treatment; a
control group: RPMC stimulated with TNF-alpha; RPMC treated by a low-dosage LNNS
group (2.5 mg/L); RPMC treated by a medium-dosage LNNS group (5 mg/L); and RPMC
treated by a high-dosage LNNS group (10 mg/L). Reverse transcription-polymerase
chain reaction was applied to test the expression of fifibronectin, collagen I
(COL-I), TGF-beta mRNA, and Western blot method to test the Smad protein 7
expression of RPMC. RESULTS: Compared with the blank group, a signifificant
elevation in fifibronectin (FN), COL-I and TGF-beta mRNA expression of RPMC were
observed in the control group (P<0.05). Compared with the control group, LNNS
suppressed the expressions of FN, COL-I and TGF-beta mRNA in a
concentrationdependent manner (P<0.05). The expression of Smad7 protein of RPMC
was down-regulated by TNF-alpha stimulation, and up-regulated with the increase
of LNNS dose (P<0.05). CONCLUSIONS: TNF-alpha may induce changes in RPMC's
viability, leading to peritoneal injury. LNNS could reverse the induction of
fifibrosis related cytokine FN, COL-I and TGF-beta, up-regulating the expression
of Smad7 by TNF-alpha in RPMC, thus attenuate peritoneal injury by repairing
mesothelial cells.
PMID- 26424292
TI - Randomized double-blind clinical trial of Moluodan () for the treatment of
chronic atrophic gastritis with dysplasia.
AB - OBJECTIVE: To assess the efficacy and safety of Moluodan () in treating dysplasia
in chronic atrophic gastritis (CAG) patients. METHODS: This was a multi-centered,
double-blind, randomized controlled trial. The total of 196 subjects were
assigned to receive either Moluodan or folic acid in a 2:1 ratio by blocked
randomization. Mucosa marking targeting biopsy (MTB) was used to insure the
accuracy and consistency between baseline and after 6-month treatment. Primary
outcomes were histological score, response rate of pathological lesions and
dysplasia disappearance rate. Secondary endpoints included gastroscopic findings,
clinical symptom and patient reported outcome (PRO) instrument. RESULTS:
Dysplasia score decreased in Moluodan group (P =0.002), significance was found
between groups (P =0.045). Dysplasia disappearance rates were 24.6% and 15.2% in
Moluodan and folic acid groups respectively, no significant differences were
found (P =0.127). The response rate of atrophy and intestinal metaplasia were
34.6% and 23.0% in Moluodan group, 24.3% and 13.6% in folic acid group. Moluodan
could improve erythema (P =0.044), and bile reflux (P =0.059), no significance
between groups. Moluodan was better than folic acid in improving epigastric pain,
epigastric suffocation, belching and decreased appetite (P <0.05), with symptom
disappearance rates of 37% to 83%. CONCLUSIONS: Moluodan improved dysplasia score
in histopathology, and erythema and bile reflux score in endoscopy, and superior
to folic acid in improving epigastric pain, epigastric suffocation, belching and
decreased appetite. [ChiCTR-TRC-00000169].
PMID- 26424294
TI - [How should cytopathology be taught?].
AB - Cytopathology is not excessively employed in the whole faculty of pathology in
Germany, in contrast to some neighboring countries. Cytopathology also suffers
from a lack of next generation cytologists, because experienced and interested
specialists as well as assistants actively engaged in cytology (ZTA, cytological
technical assistant and MTLA medical laboratory technical assistant) are only
available in limited numbers. However, cytopathological expertise is urgently
needed, not only in the diagnostics of gynecological cancer screening but also
for assessment of many non-gynecological preparations, which have nowadays become
more demanding and more complex particularly due to the technical developments in
internal medicine. In addition, adjuvant methods have become incorporated into
cytopathology, the interpretation of which must be carried out within this
specialty.This article gives a review of the status quo of cytopathology in
Germany and sketches how training and advanced education opportunities are
organized and if necessary could be improved. The course of specialist medical
training as well as the ZTA and MTLA training are described, also as a teaching
concept (e.g. microscopy of current cases, microscopy of case collections and
online microscopy). In order to provide cytopathology in Germany with a wider
perspective, a paradigm shift in the internal approach to cytology is suggested
so that the next generation can perceive this specialty not as a burden but as a
chance.
PMID- 26424293
TI - Effects of acupuncture at Baihui (GV 20) and Zusanli (ST 36) on peripheral serum
expression of MicroRNA 124, laminin and integrin beta1 in rats with cerebral
ischemia reperfusion injury.
AB - OBJECTIVE: To explore the effects of acupuncture at Baihui (GV 20) and Zusanli
(ST 36) on the peripheral serum expression of microRNA 124 (miRNA 124), laminin
and integrin beta1 in rats with cerebral ischemia reperfusion injury (CIRI).
METHODS: Seventy-two healthy male Sprague-Dawley rats were randomized into a
model group, an acupuncture group, and a sham-operated group using a random
digits table, with 24 rats per group. Each group was further randomly divided
into 1-, 3-, 5-, and 7-day subgroups based on the reperfusion time according to a
random digits table, with 6 rats in each subgroup. In the model and acupuncture
groups, CIRI was induced using the thread occlusion method. Electroacupuncture
stimulation was applied daily to GV 20 and left ST 36 for 20 min at the indicated
time points after successful operations. Serum was sampled for detecting laminin
and integrin beta1 protein via enzyme-linked immunosorbent assay, and serum miRNA
124 was examined using quantitative polymerase chain reaction. RESULTS: The serum
level of miRNA 124 in the cerebral ischemia rats increased significantly, and the
peak expression of miRNA 124 in both the model and acupuncture groups occurred at
3 days. The expression of miRNA 124 in the acupuncture group was higher than in
the model group at the same time point (5.96+/-0.01 vs. 3.11+/-0.04, P <0.05).
Laminin expression in serum from the cerebral ischemia group was higher than that
in the sham-operated group. Compared with the model group, the level of laminin
in the serum of the acupuncture group was significantly lower at each time point,
especially at the 3-day, and 7-day time points (589.12+/-3.57 vs. 793.05+/-5.28,
and 600.53+/-3.05 vs. 899.06+/-5.74, P <0.05). The level of integrin beta1 in the
serum from the acupuncture group was lower than that in the model group
particularly at the 3-day and 7-day time points (208.66+/-0.95 vs. 280.83+/-1.77,
and 212.36+/-0.95 vs. 316.77+/-2.42, P <0.05). Additionally, the model group and
the acupuncture group showed dual peaks of integrin beta1 and laminin expression
at 3-day and 7-day. CONCLUSIONS: Acupuncture at GV 20 and ST 36 in rats
alleviated CIRI and was associated with upregulated expression of miRNA 124 and
with downregulated expression of integrin beta1 and laminin in peripheral serum.
These changes may represent one of the mechanisms underlying acupuncture's
attenuation of CIRI.
PMID- 26424295
TI - Diagnostic cutoff for pressure drop coefficient in relation to fractional flow
reserve and coronary flow reserve: A patient-level analysis.
AB - OBJECTIVES AND BACKGROUND: Functional assessment of intermediate coronary
stenosis during cardiac catheterization is conducted using diagnostic parameters
like fractional flow reserve (FFR), coronary flow reserve (CFR), hyperemic
stenosis resistance index (HSR), and hyperemic microvascular resistance (HMR).
CDP (ratio of pressure drop across a stenosis to distal dynamic pressure), a
nondimensional index derived from fundamental fluid dynamic principles, based on
a combination of intracoronary pressure, and flow measurements may improve the
functional assessment of coronary lesion severity. METHODS: Patient-level data
pertaining to 350 intracoronary pressure and flow measurements across coronary
stenoses was assessed to evaluate CFR, FFR, HSR, HMR, and CDP. CDP was calculated
as (DeltaP)/(0.5 * rho * APV(2)). The density of blood (rho) was assumed to be
1.05 g/cm(3). The correlation of current diagnostic parameters (CFR, FFR, HSR,
and HMR) with CDP was evaluated. The receiver operating characteristic (ROC)
curve was used to identify the optimal cut-off point of CDP, corresponding to the
clinically used cut-off values (FFR = 0.80 and CFR = 2.0). RESULTS: CDP
correlated significantly with FFR (r = 0.81, P < 0.05) and had significant
diagnostic efficiency (ROC-area under curve of 86%), specificity (72%) and
sensitivity (85%) at FFR < 0.8. The corresponding cut-off value for CDP to detect
FFR < 0.8 was at CDP>25.4. CDP also correlated significantly (r = 0.98, P < 0.05)
with epicardial-specific parameter, HSR. CONCLUSIONS: CDP, a functional parameter
based on both intracoronary pressure and flow measurements, has close agreement
(area under ROC curve = 86%) with FFR, the frequently used method of evaluating
stenosis severity.
PMID- 26424297
TI - Serum Cholinesterase Is Inversely Associated with Body Weight Change in Men
Undergoing Routine Health Screening.
AB - OBJECTIVE: The purpose of this study is to investigate the relationships between
serum cholinesterase and body weight change, in addition to incident obesity
defined as a body mass index (BMI) of 25 kg/m(2) or greater. METHODS: A
retrospective 5-year follow-up study was conducted. The crude incidence and
hazard ratios (HRs) of obesity adjusted for the BMI and other confounders were
calculated for cholinesterase quartiles in 1,412 men and 921 women. Partial
correlation coefficients (PCCs) were calculated between cholinesterase and
changes in the BMI during the 5-year follow-up period adjusted for age and other
confounders and the change in the BMI were compared among cholinesterase
quartiles in 1,223 men and 681 women. RESULTS: During the 5-year follow-up
period, 149 men (10.6%) and 65 women (7.1%) developed obesity. The adjusted HRs
of obesity decreased, although the crude incidence of obesity increased along the
quartiles of cholinesterase in men. The adjusted HRs of obesity for the first
(lowest), second and third quartiles of cholinesterase were 2.02 (p=0.006), 1.45
(p=0.122), and 1.28 (p=0.265), respectively compared with the highest quartile in
men. The PCC between the baseline level of cholinesterase and change in the BMI
was -0.16 (p<0.001) in men. The mean changes in BMI for 5 years were 0.31
kg/m(2), 0.17 kg/m(2), 0.01 kg/m(2) and -0.04 kg/m(2), respectively in the first,
second, third and fourth quartiles of cholinesterase in men (p=0.005). Neither
incident obesity nor weight gain was significantly associated with cholinesterase
in women. CONCLUSION: The serum cholinesterase level was inversely associated
with body weight change, as well as incident obesity, after adjusted for the BMI
in men.
PMID- 26424296
TI - Interventions for preventing or treating malnutrition in problem drinkers who are
homeless or vulnerably housed: protocol for a systematic review.
AB - BACKGROUND: Problem alcohol drinking in homeless and vulnerably housed people can
lead to malnutrition, which is associated with complications such as alcohol
related brain damage. Homeless alcohol drinkers are likely to have worse health
outcomes and different nutritional needs compared with housed alcohol-drinking
persons. It is not clear whether interventions to improve nutritional status in
this population have been effective. The purpose of this review is to assess the
effectiveness and cost-effectiveness of interventions for preventing or
correcting micronutrient deficiencies and other forms of malnutrition and related
comorbidities in this population. METHODS/DESIGN: A systematic search for studies
of a nutrition-based intervention applied in the homeless or vulnerably housed
population with problem drinking will be conducted. The following electronic
databases will be systematically searched for relevant studies: MEDLINE, EMBASE,
Web of Science, PsycINFO, CAB abstracts, CINAHL, Cochrane Public Health Group
Register and Cochrane Drugs and Alcohol Group Register. Screening of identified
abstracts for relevance and assessment of papers for inclusion will be done in
duplicate. One reviewer will extract data from the studies and assess quality,
and this will be checked by another reviewer. Discrepancies will be resolved by
consensus. The primary outcomes are (mal)nutrition status or micronutrient
deficiencies or change in (mal)nutrition status or micronutrient deficiencies,
measures of liver damage and cognitive function. Secondary outcomes include
comorbidities, quality of life and functional scales, resources used to deliver
treatment, uptake/acceptability of the intervention and engagement with treatment
services. Results will be analysed descriptively, and, if appropriate, meta
analyses will be performed. DISCUSSION: The results of this review should help to
inform the development of effective interventions that can be implemented in the
community to improve the health of homeless people who are problem drinkers.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024247.
PMID- 26424298
TI - Clinical Features of Ischemic Stroke during Treatment with Dabigatran: An
Association between Decreased Severity and a Favorable Prognosis.
AB - OBJECTIVE: Anticoagulation therapy with warfarin is associated with a favorable
prognosis in ischemic stroke. Dabigatran, a new oral anticoagulant, is widely
used to prevent ischemic stroke in non-valvular atrial fibrillation (NVAF)
patients. However, its association with decreased severity and a favorable
prognosis once ischemic stroke has occurred remains unknown. METHODS: We
retrospectively reviewed all the patients with NVAF-associated ischemic stroke
admitted to our hospital from April 2011 to December 2014 and included those who
received dabigatran therapy. We assessed whether the patients were under regular
use of the drug or discontinuance and classified them into 2 groups, the
treatment and discontinuation groups. Clinical data, including the age, sex,
ASCOD stroke phenotype, NVAF type, prescribed drug dose, comorbidities, CHADS2
score, renal function, National Institute of Health Stroke Scale (NIHSS) score on
admission, modified Rankin scale (mRS) score at discharge, D-dimer, and brain
natriuretic peptide, were investigated and compared between the groups. RESULTS:
Nine patients were under regular dabigatran therapy, and 6 were under
discontinuance of the drug. The age, sex, ASCOD stroke phenotype, NVAF type,
comorbidities, renal function, and CHADS2 scores did not differ between the 2
groups; however, the NIHSS scores were significantly lower in the treatment
group. The mRS scores at discharge were additionally decreased in the treatment
group. Moreover, the D-dimer scores were lower in the treatment group, thus
suggesting a possible role in the decreased stroke severity. CONCLUSION:
Dabigatran may therefore decrease the severity of ischemic stroke, even if
ischemic stroke occurs.
PMID- 26424299
TI - True Primary Enterolith Treated by Balloon-assisted Enteroscopy.
AB - Primary enterolith is a rare condition that can induce ileus and intestinal
perforation. We report the first case of a true primary enterolith treated by
balloon-assisted enteroscopy. The patient presented with a small intestinal
ileus. After its improvement following the insertion of an ileus tube,
radiography with amidotrizoate sodium meglumine detected a round, movable defect
in the ileum measuring 42 mm diameter. The patient was diagnosed with a primary
enterolith based on her past history. The enterolith was fractured and removed
using balloon-assisted enteroscopy. This case suggests that balloon-assisted
enteroscopy may be an effective non-invasive treatment option for enteroliths.
PMID- 26424300
TI - Acute Liver Failure Complicated with Severe Heart Failure.
AB - A young pregnant woman was hospitalized due to hepatitis B virus (HBV)-related
acute liver failure (ALF). The cardiac function was normal on admission. However,
she developed ALF concurrently with a coma and severe cardiac failure. The
patient was diagnosed with severe acute cardiomyopathy due to diffuse hypokinesis
of the left ventricle wall on ultrasound cardiography. Following intensive
treatment, both the liver and cardiac function dramatically recovered. Although
some factors, such as HBV, pregnancy and systemic inflammatory response syndrome,
are possible causes of acute cardiomyopathy in the present case, ALF itself may
be a risk factor for heart failure.
PMID- 26424301
TI - Rate-dependent Loss of Capture during Ventricular Pacing.
AB - A 63-year-old patient who had undergone atrial septal defect surgical repair
received implantation of a single chamber VVI pacemaker for long RR intervals
during atrial fibrillation. One week later, an intermittent loss of capture and
sensing failure was detected at a pacing rate of 70 beats/min. However, a
successful capture was observed during rapid pacing. Consequently, the pacing
rate was temporarily adjusted to 90 beats/min. At the 3-month follow-up, the
pacemaker was shown to be functioning properly independent of the pacing rate. An
echocardiogram showed that the increased pacing rates were accompanied by a
reduction in the right ventricular outflow tract dimension. The pacemaker was
then permanently programmed at a lower rate of 60 beats/min.
PMID- 26424302
TI - Coronary Artery Pseudoaneurysm due to Medial Mucoid Degeneration Mimicking an
Intra-atrial Mass.
AB - Coronary artery aneurysms are frequently asymptomatic and may be difficult to
diagnose by cardiac imaging. We herein present a case of a coronary artery
aneurysm of the right coronary artery due to medial mucoid degeneration mimicking
an intra-atrial mass on echocardiography and magnetic resonance imaging, with the
cause being diagnosed after surgery.
PMID- 26424303
TI - A Sickle Cell Disease Patient with Severe Tricuspid Regurgitation and Early
Developed Pulmonary Hypertension.
AB - Pulmonary hypertension (PH) worsens the mortality of the patients with sickle
cell disease (SCD). The exact mechanism of PH development/progression in SCD,
including the role of tricuspid regurgitation (TR), remains unclear. We herein
report an unusual SCD case, complicated by chronic thromboembolic disorder, who
developed severe TR and an accelerated progression of PH. Tricuspid valve surgery
significantly ameliorated the patient's symptoms and reduced hospital
readmission. The early detection and management of the reversible disorder
accelerating the PH development in SCD patients may alter the clinical course,
improve the quality of life, and potentially affect the long-term outcome.
PMID- 26424304
TI - Isolated Atrial Septal Defect Complicated by Tricuspid Valve Infective
Endocarditis.
AB - Infective endocarditis (IE) associated with atrial septal defect (ASD) is
extremely rare. However, tricuspid regurgitation (TR) secondary to right
ventricular overload is a potential cause of IE, and once it occurs, the
development of a paradoxical embolism may lead to fatal complications. We herein
report the case of a 50-year-old woman who was admitted due to a persistent fever
resistant to antibiotics. Echocardiography showed secundum ASD, moderate TR and a
mobile vegetation measuring 15*10 mm attached to the tricuspid valve. Given the
risk of developing a paradoxical embolism, urgent surgery was successfully
performed.
PMID- 26424305
TI - Successful Treatment with an Antihypertensive Drug Regimen Including Eplerenone
in a Patient with Malignant Phase Hypertension with Renal Failure.
AB - A 28-year-old man was referred to our hospital for the treatment of congestive
heart failure and severe hypertension. The patient was diagnosed with malignant
phase hypertension based on the presence of marked hypertension with left
ventricular hypertrophy, exudate retinopathy, and renal failure. Intensive
therapy for hypertension and heart failure with a combination of antihypertensive
drugs including nitroglycerin, nifedipine, eplerenone and candesartan
successfully lowered his blood pressure and further improved the renal function.
Eplerenone could be one of the choices of antihypertensive drugs in combination
therapy in patients with malignant phase hypertension with progressive heart and
renal failure.
PMID- 26424306
TI - Dramatic Improvement of Diabetes Mellitus Following the Treatment of Coexisting
Acromegaly and Cushing's Syndrome.
AB - Endocrine diseases are frequently accompanied by diabetes mellitus and treatment
of an underlying endocrine disease often improves glucose control. The co
occurrence of acromegaly and Cushing's syndrome is extremely rare. We herein
describe a patient who showed a dramatic improvement in glucose control following
treatment for co-existing acromegaly and Cushing's syndrome. An adrenal mass was
incidentally discovered during a routine evaluation of a 56-year-old woman who
was subsequently diagnosed with acromegaly and a unilateral cortisol-producing
adrenal adenoma. Her blood glucose was poorly controlled despite receiving high
dose insulin therapy. After undergoing adrenalectomy for Cushing's syndrome, her
insulin dosage was decreased by almost 50%. The insulin treatment was
discontinued following the treatment of acromegaly.
PMID- 26424307
TI - A Novel Missense Mutation of the MEN1 Gene in a Patient with Multiple Endocrine
Neoplasia Type 1 with Glucagonoma and Obesity.
AB - A 35-year-old obese diabetic man presented with recurrent primary
hyperparathyroidism during a three-year outpatient follow-up. He was clinically
diagnosed with multiple endocrine neoplasia type 1 (MEN1) due to the presence of
a pituitary adenoma and multiple glucagonomas. The glucagonomas may have affected
his glycemic control. However, he did not demonstrate weight loss, suggesting
that the patient's obesity could have obscured the early diagnosis of a
glucagonoma. Genetic testing revealed a novel missense mutation at codon 561 in
exon 10, resulting in an amino acid substitution from methionine to arginine
(M561R) in the MEN1 gene. This mutation appeared to be responsible for the MEN1
pathogenicity.
PMID- 26424308
TI - Pulmonary Sarcoidosis Presenting with Miliary Opacities.
AB - Lung lesions often appear in patients with sarcoidosis; however, miliary
opacities are rare. We herein report the case of a 40-year-old woman with
pulmonary sarcoidosis who presented with dyspnea on exertion. Subsequent computed
tomography showed miliary opacities, and the presence of granulomas was confirmed
by a transbronchial lung biopsy. Glucocorticoid therapy was initiated and the
symptoms and miliary opacities rapidly improved. Although miliary sarcoidosis is
uncommon, physicians should consider sarcoidosis in addition to tuberculosis,
malignancy, and pneumoconiosis when presented with miliary opacities.
PMID- 26424309
TI - Life-threatening and Rapidly Growing Teratoma in the Anterior Mediastinum.
AB - This report describes the case of a 23-year-old man with a mediastinal teratoma.
Five months before admission, a chest radiograph during a routine health checkup
was normal. Four months before admission, the patient developed sudden onset of
mild right-sided chest pain. He gradually developed dyspnea and was admitted to
our hospital. Computed tomography revealed a giant tumor that was markedly
compressing the right atrium. Urgent surgery was performed, and a ruptured,
benign mature teratoma was diagnosed. Mature mediastinal teratomas are benign
tumors, but they can rupture and have the potential to grow rapidly, potentially
leading to life-threatening complications.
PMID- 26424310
TI - An Autopsy Case of Two Distinct, Acquired Drug Resistance Mechanisms in Epidermal
Growth Factor Receptor-mutant Lung Adenocarcinoma: Small Cell Carcinoma
Transformation and Epidermal Growth Factor Receptor T790M Mutation.
AB - We herein describe the case of a 63-year-old man who died from relapsed epidermal
growth factor receptor gene (EGFR) exon 19 deletion lung adenocarcinoma treated
with erlotinib. According to the autopsy results, he was confirmed to have small
cell carcinoma without the EGFR T790M mutation in his pancreas and left kidney
metastatic specimens, while the adenocarcinoma metastatic lesion in his right
kidney had the EGFR T790M mutation; both retained the somatic EGFR exon 19
deletion. We herein report an autopsy case of resistance to an EGFR tyrosine
kinase inhibitor via small cell carcinoma transformation and the EGFRT790M
mutation in separate metastatic organs.
PMID- 26424311
TI - Anti-MuSK Antibody-positive Myasthenia Gravis Mimicking Amyotrophic Lateral
Sclerosis.
AB - We herein investigated the clinical features of three patients with anti-muscle
specific tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG), which
was initially difficult to distinguish from amyotrophic lateral sclerosis (ALS).
The patients exhibited dropped head syndrome or dysphagia as initial symptoms.
Although their clinical findings were compatible with the revised El Escorial
Criteria for ALS, their progression appeared to be more rapid than that of ALS.
Both the edrophonium and repetitive nerve stimulation tests yielded negative
results, and diurnal fluctuation was not confirmed. The patients were ultimately
diagnosed with anti-MuSK antibody-positive MG. We therefore recommend the
measurement of anti-MuSK antibodies when encountering such cases.
PMID- 26424312
TI - A Patient with the GLA p.E66Q Mutation Exhibiting Vascular Parkinsonism and
Bilateral Pulvinar Lesions.
AB - A 76-year-old man was admitted to our hospital due to gait difficulty. Brain
imaging indicated bilateral pulvinar lesions and moderate white matter lesions.
The serum alpha-galactosidase A levels were measured for the differential
diagnosis of bilateral pulvinar lesions and were found to be abnormally low.
Therefore, the patient was suspected to have variant Fabry disease. A GLA
mutation analysis showed the p.E66Q mutation, which is speculated to be a
functional polymorphism rather than a disease-causing mutation of Fabry disease.
Enzyme replacement therapy did not result in a marked improvement, however, the
disease progression stopped.
PMID- 26424313
TI - Refractory Dermatomyositis Complicated with Myelodysplastic Syndrome.
AB - We herein describe a case of refractory dermatomyositis (DM) complicated with
myelodysplastic syndrome (MDS). Despite intensive immunosuppressive therapies,
the activity of myositis, skin ulcers, and interstitial pneumonia did not
improve. The patient ultimately died following the progression of interstitial
pneumonia. There are few reports of DM accompanying MDS to date, and any
association in the pathogenesis between the two is still unclear. However,
underlying MDS may have the potential to influence the therapeutic response of
DM.
PMID- 26424314
TI - Falciparum Malaria Incidentally Pretreated with Azithromycin.
AB - A 65-year-old man, who recently returned from Liberia, visited a clinic
complaining of fever, and azithromycin was prescribed. The patient presented to a
general hospital 5 days after the onset of symptoms, however, a blood smear
examination failed to detect malaria. Contrary to the blood smear result, a rapid
antigen test in our hospital was strongly-positive for falciparum malaria,
indicating a high level of malarial antigen in the blood. Moreover, laboratory
examinations on admission showed a tendency for improvement. We assumed that the
administration of azithromycin partially treated malaria, thus complicating the
blood smear diagnosis. We should be careful in prescribing azithromycin, which is
widely used in clinics, to travelers returning from malaria-endemic countries.
PMID- 26424315
TI - Pregnant Woman Bitten by a Japanese Mamushi (Gloydius blomhoffii).
AB - We herein report the fourth case of a pregnant woman bitten by a mamushi. A 33
year-old pregnant woman in the 25th week of gestation was bitten by a mamushi.
Her vital signs were stable; however, biochemical analyses of the blood showed
mild deterioration of anemia and hypoproteinemia. The effects of envenomation
were limited to the extremities, the administration of supportive therapy without
antivenom fortunately resulted in a favorable outcome. As there are differences
in the maternal medical condition and weeks of gestation, further research is
needed to clarify the optimal management strategy for administering antivenom in
pregnancy.
PMID- 26424316
TI - Multiple Osteonecrosis with Systemic Lupus Erythematosus.
PMID- 26424317
TI - Uterine Leiomyosarcoma Presenting with a Fever of Unknown Origin.
PMID- 26424318
TI - Othello Pica: A Clue of Recurrent Rectal Cancer.
PMID- 26424319
TI - Deep Vein Thrombosis due to Metastatic Bladder Cancer.
PMID- 26424320
TI - Dumping Syndrome due to the Misplacement of the Gastrostomy Feeding Tube.
PMID- 26424321
TI - Human Papillomavirus (HPV) Vaccination Safety Assessment: The Methods Matter.
PMID- 26424322
TI - Human Papillomavirus (HPV) Vaccination Safety Assessment: The Methods Matter.
PMID- 26424323
TI - Reciprocal Alterations in Regulator of G Protein Signaling 4 and microRNA16 in
Schizophrenia.
AB - N-methyl-d-aspartate receptor (NMDAR) hypofunction in the dorsolateral prefrontal
cortex (DLPFC) has been implicated in the pathology of schizophrenia. NMDAR
activity is negatively regulated by some G protein-coupled receptors (GPCRs).
Signaling through these GPCRs is reduced by Regulator of G protein Signaling 4
(RGS4). Thus, lower levels of RGS4 would enhance GPCR-mediated reductions in
NMDAR activity and could contribute to NMDAR hypofunction in schizophrenia. In
this study, we quantified RGS4 mRNA and protein levels at several levels of
resolution in the DLPFC from subjects with schizophrenia and matched healthy
comparison subjects. To investigate molecular mechanisms that could contribute to
altered RGS4 levels, we quantified levels of small noncoding RNAs, known as
microRNAs (miRs), which regulate RGS4 mRNA integrity after transcription. RGS4
mRNA and protein levels were significantly lower in schizophrenia subjects and
were positively correlated across all subjects. The RGS4 mRNA deficit was present
in pyramidal neurons of DLPFC layers 3 and 5 of the schizophrenia subjects. In
contrast, levels of miR16 were significantly higher in the DLPFC of schizophrenia
subjects, and higher miR16 levels predicted lower RGS4 mRNA levels. These
findings provide convergent evidence of lower RGS4 mRNA and protein levels in
schizophrenia that may result from increased expression of miR16. Given the role
of RGS4 in regulating GPCRs, and consequently the strength of NMDAR signaling,
these findings could contribute to the molecular substrate for NMDAR hypofunction
in DLPFC pyramidal cells in schizophrenia.
PMID- 26424324
TI - Distribution and transmission of Mycobacterium tuberculosis complex lineages
among children in peri-urban Kampala, Uganda.
AB - BACKGROUND: To gain insight into the transmission of tuberculosis (TB) in peri
urban Kampala-Uganda, we performed a household contact study using children as a
surrogate for recent transmission of Mycobacterium tuberculosis (MTB). Using this
approach, we sought to understand M. tuberculosis complex (MTBC) lineage
diversity, distribution and how these relate to TB transmission to exposed
children. METHOD: MTBC isolates from children aged <= 15 years, collected from
2002 to 2010 in a household-contact study, were analyzed using a LightCycler RT
PCR SNP genotyping assay (LRPS). The resultant genotypic data was used to
determine associations between MTBC lineage and the children's clinical and
epidemiological characteristics. RESULTS AND DISCUSSION: Of the 761 children
surveyed, 9% (69/761) had culture-positive TB an estimate in the range of global
childhood TB; of these 71% (49/69) were infected with an MTBC strain of the
"Uganda family", 17% (12/69) infected with MTBC lineage 4 strains other than MTBC
Uganda family and 12% (8/69) infected with MTBC lineage 3, thereby
disproportionately causing TB in the study area. Overall the data showed no
correlation between the MTBC lineages studied and transmission (OR = 0.304; P
value = 0.251; CI: 95%; 0.039-2.326) using children a proxy for TB transmission.
CONCLUSIONS: Our findings indicate that MTBC Uganda family strains are the main
cause of TB in children in peri-urban Kampala. Furthermore, MTBC lineages did not
differ in their transmissibility to children.
PMID- 26424325
TI - Impact of the Surveillance Interval on the Survival of Patients Who Undergo
Curative Surgery for Gastric Cancer.
AB - BACKGROUND: For patients who undergo gastrectomy for gastric cancer, systematic
follow-up evaluation to detect recurrent lesions is recommended, although the
benefits of a surveillance program using short-term imaging studies have not been
evaluated. METHODS: This study reviewed the clinical data of patients who
underwent curative surgery for gastric cancer using a prospective database.
Patients with recurrence were classified according to surveillance interval as
follows: <=3, 3-6, and 6-12 months. RESULTS: Of the 2785 patients who underwent
curative surgery for gastric cancer, 376 (13.5 %) had intraabdominal recurrences,
excluding the stomach. Multivariable analysis showed that a short surveillance
interval did not increase the post-recurrence survival duration (with 6-12 months
as the reference: <=3 months: hazard ratio [HR] 0.954; 95 % confidence interval
[CI] 0.689-1.323; 3-6 months: HR 0.994, 95 % CI 0.743-1.330). In addition, short
surveillance intervals did not increase overall survival (with 6-12 months as the
reference: <=3 months: HR 0.969; 95 % CI 0.699-1.342; 3-6 months: HR 0.955; 95 %
CI 0.711-1.285). In contrast to the surveillance interval, age, cancer stage,
symptoms at recurrence, and recurrence time after gastrectomy were factors
associated with both post-recurrence survival and overall survival. CONCLUSIONS:
Although the detection of recurrence before symptoms helped to prolong both post
recurrence survival and overall survival, shortening the surveillance interval to
less than 6 months did not improve either the patient's post-recurrence survival
or overall survival. Hence, it is not recommended that asymptomatic patients
undergo surveillance involving imaging studies more often than once a year.
PMID- 26424327
TI - Effectiveness of the Restore4Stroke self-management intervention "Plan ahead!": A
randomized controlled trial in stroke patients and partners.
AB - OBJECTIVE: To investigate the effectiveness of a self-management intervention
aimed at proactive coping for stroke patients and partners, compared with an
education intervention. DESIGN: Multicentre randomized controlled trial.
PARTICIPANTS: The study included 113 stroke patients (mean age 57.0 years
(standard deviation (SD) 9.0), mean 18.8 months after stroke (SD 28.4)) and 57
partners (mean age 59.2 years (SD 8.3)). METHODS: Participants were randomized to
a self-management intervention, or an education intervention, both 10 weeks'
duration, outpatient, stroke-specific, and group-based. Main patient inclusion
criteria were symptomatic stroke (>= 6 weeks previously) and reporting >= 2
restrictions on the Restriction subscale of the Utrecht Scale for Evaluation of
Rehabilitation Participation. Measurements were performed immediately after
intervention, and at 3 and 9 months follow-up. Primary patient and partner
outcomes were proactive coping and participation restrictions. Analyses were
based on linear mixed modelling. RESULTS: A significant effect was found only in
partners' increased proactive coping at T2 (compared with education
intervention). Beneficial trends were found for the self-manage-ment intervention
in partners' self-efficacy and patients' health-related quality of life, mood
complaints and participation restriction. CONCLUSION: Little convincing evidence
was found favouring our self-management intervention over the education
intervention; therefore, the self-management intervention should not be
implemented yet in clinical practice. Further research is needed to explore
beneficial trends.
PMID- 26424326
TI - Mosquito age and avian malaria infection.
AB - BACKGROUND: The immune system of many insects wanes dramatically with age,
leading to the general prediction that older insects should be more susceptible
to infection than their younger counterparts. This prediction is however
challenged by numerous studies showing that older insects are more resistant to a
range of pathogens. The effect of age on susceptibility to infections is
particularly relevant for mosquitoes given their role as vectors of malaria and
other diseases. Despite this, the effect of mosquito age on Plasmodium
susceptibility has been rarely explored, either experimentally or theoretically.
METHODS: Experiments were carried out using the avian malaria parasite Plasmodium
relictum and its natural vector in the field, the mosquito Culex pipiens. Both
innate immune responses (number and type of circulating haemocytes) and
Plasmodium susceptibility (prevalence and burden) were quantified in seven- and
17-day old females. Whether immunity or Plasmodium susceptibility are modulated
by the previous blood feeding history of the mosquito was also investigated. To
ensure repeatability, two different experimental blocks were carried out several
weeks apart. RESULTS: Haemocyte numbers decrease drastically as the mosquitoes
age. Despite this, older mosquitoes are significantly more resistant to a
Plasmodium infection than their younger counterparts. Crucially, however, the age
effect is entirely reversed when old mosquitoes have taken one previous non
infected blood meal. CONCLUSIONS: The results agree with previous studies showing
that older insects are often more resistant to infections than younger ones.
These results suggest that structural and functional alterations in mosquito
physiology with age may be more important than immunity in determining the
probability of a Plasmodium infection in old mosquitoes. Possible explanations
for why the effect is reversed in blood-fed mosquitoes are discussed. The
reversal of the age effect in blood fed mosquitoes implies that age is unlikely
to have a significant impact on mosquito susceptibility in the field.
PMID- 26424328
TI - Trends of patient referral to a memory clinic and towards earlier diagnosis from
1985-2009.
AB - BACKGROUND: It may be assumed that increased public awareness of dementia due to
Alzheimer's disease (AD) together with the availability of efficacious treatment
will result in diagnostic evaluation at earlier stages of cognitive decline and
diagnosis of dementia due to AD at earlier stages. METHODS: All persons that were
examined at a university based memory clinic, in Germany, between 1985 and 2009
were included. RESULTS: In the 3,951 persons identified, linear regression
analysis revealed a positive association between Mini Mental State Examination
(MMSE) score and year of initial examination (yearIE) (beta = 0.266; p < 0.001).
In the 1,821 patients diagnosed with dementia due to AD, a positive association
between MMSE score and yearIE (beta = 0.230; p < 0.001) was revealed. MMSE scores
were higher (beta = 0.195; p < 0.001) after the introduction of cholinesterase
inhibitors in Germany in 1997. CONCLUSIONS: Diagnostic evaluation of individuals
occurred at progressively earlier stages of cognitive decline. Dementia due to AD
was diagnosed at progressively earlier stages, and this trend was associated with
the availability of efficacious treatment. This is the first study on changes in
patient referral and diagnosis based on a continuous 25 years period.
PMID- 26424329
TI - Detection of Tetrodotoxins in Puffer Fish by a Self-Assembled Monolayer-Based
Immunoassay and Comparison with Surface Plasmon Resonance, LC-MS/MS, and Mouse
Bioassay.
AB - The increasing occurrence of puffer fish containing tetrodotoxin (TTX) in the
Mediterranean could represent a major food safety risk for European consumers and
threaten the fishing industry. The work presented herein describes the
development of a new enzyme linked immunosorbent assay (mELISA) based on the
immobilization of TTX through dithiol monolayers self-assembled on maleimide
plates, which provides an ordered and oriented antigen immobilization and favors
the antigen-antibody affinity interaction. The mELISA was found to have a limit
of detection (LOD) of TTX of 0.23 mg/kg of puffer fish matrix. The mELISA and a
surface plasmon resonance (SPR) immunosensor previously developed were employed
to establish the cross-reactivity factors (CRFs) of 5,6,11-trideoxy-TTX, 5,11
deoxy-TTX, 11-nor-TTX-6-ol, and 5,6,11-trideoxy-4-anhydro-TTX, as well as to
determine TTX equivalent contents in puffer fish samples. Results obtained by
both immunochemical tools were correlated (R(2) = 0.977). The puffer fish samples
were also analyzed using liquid chromatography-tandem mass spectrometry (LC
MS/MS), and the corresponding CRFs were applied to the individual TTX contents.
Results provided by the immunochemical tools, when compared with those obtained
by LC-MS/MS, showed a good degree of correlation (R(2) = 0.991 and 0.979 for
mELISA and SPR, respectively). The mouse bioassay (MBA) slightly overestimated
the CRF adjusted TTX content of samples when compared with the data obtained from
the other techniques. The mELISA has been demonstrated to be fit for the purpose
for screening samples in monitoring programs and in research activities.
PMID- 26424330
TI - Effectiveness and Persistence with Liraglutide Among Patients with Type 2
Diabetes in Routine Clinical Practice--EVIDENCE: A Prospective, 2-Year Follow-Up,
Observational, Post-Marketing Study.
AB - INTRODUCTION: The aim of this study was to investigate whether the efficacy of
liraglutide observed in randomized controlled trials translates into therapeutic
benefits in the French population during routine clinical practice. METHODS: This
observational, prospective, multicenter study included 3152 adults with type 2
diabetes who had recently started or were about to start liraglutide treatment.
During 2 years of follow-up, an evaluation of the reasons for prescribing
liraglutide, maintenance dose of liraglutide, changes in combined antidiabetic
treatments, level of glycemic control, change in body weight and body mass index
(BMI), patient satisfaction with diabetes treatment and safety of liraglutide
were investigated. The primary study endpoint was the proportion of patients
still receiving liraglutide and presenting with HbA1c <7.0% after 2 years of
follow-up. RESULTS: At the end of the study, 29.5% of patients maintained
liraglutide treatment and reached the HbA(1c) target. Mean (+/-SD) HbA(1c),
fasting plasma glucose concentration, body weight and BMI were significantly
reduced from baseline [8.46% (+/-1.46) to 7.44% (+/-1.20); 180 (+/-60) to 146 (+/
44) mg/dL; 95.2 (+/-20.0) to 91.1 (+/-19.6) kg; 34.0 (+/-7.2) to 32.5 (+/-6.9)
kg/m(2); respectively, all P < 0.0001]. Patient treatment satisfaction increased,
with the mean diabetes treatment satisfaction questionnaire status version score
increasing from 22.17 (+/-7.64) to 28.55 (+/-5.79), P < 0.0001. The main adverse
event type was gastrointestinal, with a frequency of 10.9%, and the percentage of
patients suffering >=1 hypoglycemic episode decreased from 6.9% to 4.4%.
CONCLUSION: The results of the EVIDENCE study suggest that the effectiveness of
liraglutide in real-world clinical practice is similar to that observed in
randomized controlled trials. FUNDING: Novo Nordisk A/S. TRIAL REGISTRATION:
ClinicalTrials.gov identifier, NCT01226966.
PMID- 26424331
TI - Fixed Combination of Travoprost and Timolol Maleate Reduces Intraocular Pressure
in Japanese Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A
Prospective Multicenter Open-Label Study.
AB - INTRODUCTION: The efficacy of lowering intraocular pressure (IOP) and safety of
switching to travoprost/timolol fixed combination ophthalmic solution
(Duotrav((r)), Alcon Laboratories, Inc., Fort Worth, TX, USA) in patients with
primary open-angle glaucoma, normal tension glaucoma or ocular hypertension
undergoing prostaglandin analog (PGA) monotherapy was investigated. METHODS:
Patients treated with travoprost, latanoprost, tafluprost, or bimatoprost for >=3
months and requiring additional medication were switched to Duotrav without
washout. Baseline IOP was calculated from measurements at two visits during PGA
monotherapy. IOP reductions at 4, 8, and 12 weeks after switching to Duotrav and
adverse events were assessed. RESULTS: Of 162 patients enrolled, 157 patients
(96.9%) with >=4 weeks of follow-up after switching to Duotrav were analyzed. The
mean IOP decreased significantly (baseline = 16.3 +/- 3.1 mmHg; 4 weeks = 14.6 +/
3.1 mmHg, 8 weeks = 14.7 +/- 3.3 mmHg, 12 weeks = 14.6 +/- 3.2 mmHg; all P <
0.0001). When study eyes were divided into three groups according to baseline IOP
(>=19 mmHg: 33 eyes, 21.0%; >=15 to <19 mmHg: 78 eyes, 49.7%; <15 mmHg: 46 eyes,
29.3%), all groups showed significant IOP reductions (P = 0.0324 ~ P < 0.0001)
after switching to Duotrav. Twenty-seven of 166 patients (16.3%) in the safety
analysis experienced adverse events and 26/166 patients (15.7%) experienced
adverse events, for which a relationship to Duotrav could not be ruled out.
Adverse events in five patients led to treatment discontinuation (eye pruritus;
eye irritation; increased blood pressure and rash; increased blurred vision;
deepening of the eyelid sulcus and blepharoptosis). Twelve weeks after treatment
switching, eyelash changes, blepharal pigmentation and deepening of the eyelid
sulcus occurred in 42 (26.8%), 29 (18.5%), and 13 (8.3%) cases, respectively,
among 157 patients with follow-up. There was no significant worsening from
baseline for superficial punctate keratopathy (SPK) or conjunctival hyperemia
after switching (SPK score: baseline = 0.58 +/- 1.31; 12 weeks = 0.92 +/- 1.76, P
= 0.1819; conjunctival hyperemia score: baseline = 0.41 +/- 0.64; 12 weeks = 0.49
+/- 0.63, P = 0.3774). CONCLUSION: Our findings confirm that switching to
Duotrav((r)) in PGA monotherapy patients shows IOP-lowering effect with minimal
safety concerns. FUNDING: Japan Association of Health Service and Alcon Japan.
Ltd. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier, UMIN000007028.
PMID- 26424333
TI - Introduction: Complications of lumbar spine surgery.
PMID- 26424332
TI - Role of the major antigenic membrane protein in phytoplasma transmission by two
insect vector species.
AB - BACKGROUND: Phytoplasmas are bacterial plant pathogens (class Mollicutes),
transmitted by phloem feeding leafhoppers, planthoppers and psyllids in a
persistent/propagative manner. Transmission of phytoplasmas is under the control
of behavioral, environmental and geographical factors, but molecular interactions
between membrane proteins of phytoplasma and vectors may also be involved. The
aim of the work was to provide experimental evidence that in vivo interaction
between phytoplasma antigenic membrane protein (Amp) and vector proteins has a
role in the transmission process. In doing so, we also investigated the topology
of the interaction at the gut epithelium and at the salivary glands, the two
barriers encountered by the phytoplasma during vector colonization. METHODS:
Experiments were performed on the 'Candidatus Phytoplasma asteris' chrysanthemum
yellows strain (CYP), and the two leafhopper vectors Macrosteles
quadripunctulatus Kirschbaum and Euscelidius variegatus Kirschbaum. To
specifically address the interaction of CYP Amp at the gut epithelium barrier,
insects were artificially fed with media containing either the recombinant
phytoplasma protein Amp, or the antibody (A416) or both, and transmission,
acquisition and inoculation efficiencies were measured. An abdominal
microinjection protocol was employed to specifically address the interaction of
CYP Amp at the salivary gland barrier. Phytoplasma suspension was added with Amp
or A416 or both, injected into healthy E. variegatus adults and then infection
and inoculation efficiencies were measured. An internalization assay was
developed, consisting of dissected salivary glands from healthy E. variegatus
exposed to phytoplasma suspension alone or together with A416 antibody. The
organs were then either observed in confocal microscopy or subjected to DNA
extraction and phytoplasma quantification by qPCR, to visualize and quantify
possible differences among treatments in localization/presence/number of CYP
cells. RESULTS: Artificial feeding and abdominal microinjection protocols were
developed to address the two barriers separately. The in vivo interactions
between Amp of 'Candidatus Phytoplasma asteris' Chrysanthemum yellows strain
(CYP) and vector proteins were studied by evaluating their effects on phytoplasma
transmission by Euscelidius variegatus and Macrosteles quadripunctulatus
leafhoppers. An internalization assay was developed, consisting of dissected
salivary glands from healthy E. variegatus exposed to phytoplasma suspension
alone or together with anti-Amp antibody. To visualize possible differences among
treatments in localization/presence of CYP cells, the organs were observed in
confocal microscopy. Pre-feeding of E. variegatus and M. quadripunctulatus on
anti-Amp antibody resulted in a significant decrease of acquisition efficiencies
in both species. Inoculation efficiency of microinjected E. variegatus with CYP
suspension and anti-Amp antibody was significantly reduced compared to that of
the control with phytoplasma suspension only. The possibility that this was due
to reduced infection efficiency or antibody-mediated inhibition of phytoplasma
multiplication was ruled out. These results provided the first indirect proof of
the role of Amp in the transmission process. CONCLUSION: Protocols were developed
to assess the in vivo role of the phytoplasma native major antigenic membrane
protein in two phases of the vector transmission process: movement through the
midgut epithelium and colonization of the salivary glands. These methods will be
useful also to characterize other phytoplasma-vector combinations. Results
indicated for the first time that native CYP Amp is involved in vivo in specific
crossing of the gut epithelium and salivary gland colonization during early
phases of vector infection.
PMID- 26424334
TI - Lumbar pseudarthrosis: a review of current diagnosis and treatment.
AB - OBJECT Failed solid bony fusion, or pseudarthrosis, is a well-known complication
of lumbar arthrodesis. Recent advances in radiographic technology, biologics,
instrumentation, surgical technique, and understanding of the local biology have
all aided in the prevention and treatment of pseudarthrosis. Here, the current
literature on the diagnosis and management of lumbar pseudarthroses is reviewed.
METHODS A systematic literature review was conducted using the MEDLINE and Embase
databases in order to search for the current radiographie diagnosis and surgical
treatment methods published in the literature (1985 to present). Inclusion
criteria included: 1) published in English; 2) level of evidence I-III; 3)
diagnosis of degenerative lumbar spine conditions and/or history of lumbar spine
fusion surgery; and 4) comparative studies of 2 different surgical techniques or
comparative studies of imaging modality versus surgical exploration. RESULTS
Seven studies met the inclusion criteria for current radiographie imaging used to
diagnose lumbar pseudarthrosis. Plain radiographs and thin-cut CT scans were the
most common method for radiographie diagnosis. PET has been shown to be a valid
imaging modality for monitoring in vivo active bone formation. Eight studies
compared the surgical techniques for managing and preventing failed lumbar
fusion. The success rates for the treatment of pseudarthrosis are enhanced with
the use of rigid instrumentation. CONCLUSIONS Spinal fusion rates have improved
secondary to advances in biologies, instrumentation, surgical techniques, and
understanding of local biology. Treatment of lumbar pseudarthrosis includes a
variety of surgical options such as replacing loose instrumentation, use of more
potent biologies, and interbody fusion techniques. Prevention and recognition are
important tenets in the algorithm for the management of spinal pseudarthrosis.
PMID- 26424335
TI - Complications from the use of intrawound vancomycin in lumbar spinal surgery: a
systematic review.
AB - OBJECT The use of intrawound vancomycin is rapidly being adopted for the
prevention of surgical site infection (SSI) in spinal surgery. At operative
closure, the placement of vancomycin powder in the wound bed-in addition to
standard infection prophylaxis-can provide high concentrations of antibiotics
with minimal systemic absorption. However, despite its popularity, to date the
majority of studies on intrawound vancomycin are retrospective, and there are no
prior reports highlighting the risks of routine treatment. METHODS A MEDLINE
search for pertinent literature was conducted for studies published between 1966
and May 2015 using the following MeSH search terms: "intrawound vancomycin,"
"operative lumbar spine complications," and "nonoperative lumbar spine
complications." This was supplemented with references and known literature on the
topic. RESULTS An advanced MEDLINE search conducted on May 6, 2015, using the
search string "intrawound vancomycin" found 22 results. After a review of all
abstracts for relevance to intrawound vancomycin use in spinal surgery, 10
studies were reviewed in detail. Three meta-analyses were evaluated from the
initial search, and 2 clinical studies were identified. After an analysis of all
of the identified manuscripts, 3 additional studies were included for a total of
16 studies. Fourteen retrospective studies and 2 prospective studies were
identified, resulting in a total of 9721 patients. A total of 6701 (68.9%)
patients underwent treatment with intrawound vancomycin. The mean SSI rate among
the control and vancomycin-treated patients was 7.47% and 1.36%, respectively.
There were a total of 23 adverse events: nephropathy (1 patient), ototoxicity
resulting in transient hearing loss (2 patients), systemic absorption resulting
in supratherapeutic vancomycin exposure (1 patient), and culture-negative seroma
formation (19 patients). The overall adverse event rate for the total number of
treated patients was 0.3%. CONCLUSIONS Intrawound vancomycin use appears to be
safe and effective for reducing postoperative SSIs with a low rate of morbidity.
Study disparities and limitations in size, patient populations, designs, and
outcomes measures contribute significant bias that could not be fully rectified
by this systematic review. Moreover, care should be exercised in the use of
intrawound vancomycin due to the lack of well-designed, prospective studies that
evaluate the efficacy of vancomycin and include the appropriate systems to
capture drug-related complications.
PMID- 26424336
TI - Complications of intraoperative epidural steroid use in lumbar discectomy: a
systematic review and meta-analysis.
AB - OBJECT The authors' aim in this paper was to review the intraoperative use of
epidural steroids in lumbar discectomy surgery with a focus on surgical
complications. METHODS A comprehensive literature search was done using PubMed,
MEDLINE, and the Cochrane Central Registry of Controlled Trials. Relevant papers
were retrieved and analyzed. The authors performed a meta-analysis of all
available data. Search terms included epidural, steroids, discectomy, lumbar disc
surgery, herniated lumbar disc, methylprednisolone, and perioperative.The primary
outcome was surgical complications such as wound infection or need for
reoperation. Secondary outcomes were pain and postoperative narcotic usage.
RESULTS Sixteen trials and 1 retrospective study (a total of 1933 patients) were
eligible for inclusion in this study. In all studies, steroids were added
epidurally over the nerve root before closure in cases, and control patients
underwent discectomy alone. The mean age (42.7 years vs 42.4 years; RR 0.30 [95%
CI -0.30 to 0.90], p = 0.32), overall complication rates (2.69% vs 1.18%; RR 1.94
[95% CI 0.72-5.26], p = 0.19), and infectious complication rates (0.94% vs 0.08%;
RR 4.58 [95% CI 0.75-27.95], p = 0.10) were similar between the steroid group and
control group, respectively. CONCLUSIONS There is good evidence that epidural
steroids can decrease pain in the short term and decrease the usage of
postoperative narcotics after lumbar spinal surgery for degenerative spinal
disease. The authors' results demonstrate a trend toward increased infection with
epidural steroid use, but there was not a statistically significant difference.
More studies are needed to validate the long-term risk/benefit ratio of epidural
steroids in lumbar discectomy.
PMID- 26424337
TI - A population-based review of bone morphogenetic protein: associated complication
and reoperation rates after lumbar spinal fusion.
AB - OBJECT The authors compared the rates of postoperative adverse events and
reoperation of patients who underwent lumbar spinal fusion with bone
morphogenetic protein (BMP) to those of patients who underwent lumbar spinal
fusion without BMP. METHODS The authors retrospectively analyzed the PearlDiver
Technologies, Inc., database, which contains the Medicare Standard Analytical
Files, the Medicare Carrier Files, the PearlDiver Private Payer Database
(UnitedHealthcare), and select state all-payer data sets, from 2005 to 2010. They
identified patients who underwent lumbar spinal fusion with and without BMP. The
ICD-9-CM code 84.52 was used to identify patients who underwent spinal fusion
with BMP. ICD-9-CM diagnosis codes identified complications that occurred during
the initial hospital stay. ICD-9-CM procedural codes were used to identify
reoperations within 90 days of the index procedure. The relative risks (and 95%
CIs) of BMP use compared with no BMP use (control) were calculated for the
association of any complication with BMP use compared with the control. RESULTS
Between 2005 and 2010, 460,773 patients who underwent lumbar spinal fusion were
identified. BMP was used in 30.7% of these patients. The overall complication
rate in the BMP group was 18.2% compared with 18.7% in the control group. The
relative risk of BMP use compared with no BMP use was 0.976 (95% CI 0.963-0.989),
which indicates a significantly lower overall complication rate in the BMP group
(p < 0.001). In both treatment groups, patients older than 65 years had a
statistically significant higher rate of postoperative complications than younger
patients (p < 0.001). CONCLUSIONS In this large-scale institutionalized database
study, BMP use did not seem to increase the overall risk of developing a
postoperative complication after lumbar spinal fusion surgery.
PMID- 26424338
TI - Failure rates and complications of interspinous process decompression devices: a
European multicenter study.
AB - OBJECT Spacers placed between the lumbar spinous processes represent a promising
surgical treatment alternative for a variety of spinal pathologies. They provide
an unloading distractive force to the stenotic motion segment, restoring
foraminal height, and have the potential to relieve symptoms of degenerative disc
disease. The authors performed a retrospective, multicenter nonrandomized study
consisting of 1108 patients to evaluate implant survival and failure modes after
the implantation of 8 different interspinous process devices (IPDs). METHODS The
medical records of patients who had undergone placement of an IPD were
retrospectively evaluated, and demographic information, diagnosis, and
preoperative pain levels were recorded. Preoperative and postoperative clinical
assessments in the patients were based on the visual analog scale. A minimum of 3
years after IPD placement, information on long-term outcomes was obtained from
additional follow-up or from patient medical and radiological records. RESULTS
One thousand one hundred eight patients affected by symptomatic 1- or 2-level
segmental lumbar spine degenerative disease underwent placement of an IPD. The
complication rate was 7.8%. There were 27 fractures of the spinous process and 23
dura mater tears with CSF leakage. The ultimate failure rate requiring additional
surgery was 9.6%. The reasons for revision, which always involved removal of the
original implant, were acute worsening of low-back pain or lack of improvement
(45 cases), recurrence of symptoms after an initial good outcome (42 cases), and
implant dislocation (20 cases). CONCLUSIONS The IPD is not a substitute for a
more invasive 3-column fusion procedure in cases of major instability and
spondylolisthesis. Overdistraction, poor bone density, and poor patient selection
may all be factors in the development of complications. Preoperatively, careful
attention should be paid to bone density, appropriate implant size, and optimal
patient selection.
PMID- 26424339
TI - Complications related to the use of spinal cord stimulation for managing
persistent postoperative neuropathic pain after lumbar spinal surgery.
AB - OBJECT Structural spinal surgery yields improvement in pain and disability for
selected patients with spinal stenosis, spondylolisthesis, or a herniated
intervertebral disc. A significant fraction of patients exhibit persistent
postoperative neuropathic pain (PPNP) despite technically appropriate
intervention, and such patients can benefit from spinal cord stimulation (SCS) to
alleviate suffering. The complication profile of this therapy has not been
systematically assessed and, thus, was the goal of this review. METHODS A
comprehensive literature search was performed to identify prospective cohorts of
patients who had PPNP following structurally corrective lumbar spinal surgery and
who underwent SCS device implantation. Data about study design, technique of SCS
lead introduction, and complications encountered were collected and analyzed.
Comparisons of complication incidence were performed between percutaneously and
surgically implanted systems, with the level of significance set at 0.05. RESULTS
Review of 11 studies involving 542 patients formed the basis of this work: 2
randomized controlled trials and 9 prospective cohorts. Percutaneous implants
were used in 4 studies and surgical implants were used in 4 studies; in the
remainder, the types were undefined. Lead migration occurred in 12% of cases,
pain at the site of the implantable pulse generator occurred in 9% of cases, and
wound-related complications occurred in 5% of cases; the latter 2 occurred more
frequently among surgically implanted devices. CONCLUSIONS Spinal cord
stimulation can provide for improved pain and suffering and for decreased
narcotic medication use among patients with PPNP after lumbar spinal surgery.
This study reviewed the prospective studies forming the evidence base for this
therapy, to summarize the complications encountered and, thus, best inform
patients and clinicians considering its use. There is a significant rate of minor
complications, many of which require further surgical intervention to manage,
including lead migration or implant infection, although such complications do not
directly threaten patient life or function.
PMID- 26424340
TI - Lumbar spine surgery positioning complications: a systematic review.
AB - OBJECT There are a variety of surgical positions that provide optimal exposure of
the dorsal lumbar spine. These include the prone, kneeling, knee-chest, knee
elbow, and lateral decubitus positions. All are positions that facilitate
exposure of the spine. Each position, however, is associated with an array of
unique complications that result from excessive pressure applied to the torso or
extremities. The authors reviewed clinical studies reporting complications that
arose from positioning of the patient during dorsal exposures of the lumbar
spine. METHODS MEDLINE, Scopus, and Web of Science database searches were
performed to find clinical studies reporting complications associated with
positioning during lumbar spine surgery. For articles meeting inclusion criteria,
the following information was obtained: publication year, study design, sample
size, age, operative time, type of surgery, surgical position, frame or table
type, complications associated with positioning, time to first observed
complication, long-term outcomes, and evidence-based recommendations for
complication avoidance. RESULTS Of 3898 articles retrieved from MEDLINE, Scopus,
and Web of Science, 34 met inclusion criteria. Twenty-four studies reported
complications associated with use of the prone position, and 7 studies
investigated complications after knee-chest positioning. Complications associated
with the knee-elbow, lateral decubitus, and supine positions were each reported
by a single study. Vision loss was the most commonly reported complication for
both prone and knee-chest positioning. Several other complications were reported,
including conjunctival swelling, Ischemic orbital compartment syndrome, nerve
palsies, thromboembolic complications, pressure sores, lower extremity
compartment syndrome, and shoulder dislocation, highlighting the assortment of
possible complications following different surgical positions. For prone-position
studies, there was a relationship between increased operation time and position
complications. Only 3 prone-position studies reported complications following
procedures of less than 120 minutes, 7 studies reported complications following
mean operative times of 121-240 minutes, and 9 additional studies reported
complications following mean operative times greater than 240 minutes. This
relationship was not observed for knee-chest and other surgical positions.
CONCLUSIONS This work presents a systematic review of positioning-related
complications following prone, knee-chest, and other positions used for lumbar
spine surgery. Numerous evidence-based recommendations for avoidance of these
potentially severe complications associated with intraoperative positioning are
discussed. This investigation may serve as a framework to educate the surgical
team and decrease rates of intraoperative positioning complications.
PMID- 26424341
TI - Reconstruction of open wounds as a complication of spinal surgery with flaps: a
systematic review.
AB - OBJECT A systematic review of the available evidence on the prophylactic and
therapeutic use of flaps for the coverage of complex spinal soft-tissue defects
was performed to determine if the use of flaps reduces postoperative
complications and improves patient outcomes. METHODS A PubMed database search was
performed to identify English-language articles published between 1990 and 2014
that contained the following phrases to describe postoperative wounds ("wound,"
"complex back wound," "postoperative wound," "spine surgery") and intervention
("flap closure," "flap coverage," "soft tissue reconstruction," "muscle flap").
RESULTS In total, 532 articles were reviewed with 17 articles meeting the
inclusion criteria of this study. The risk factors from the pooled analysis of
262 patients for the development of postoperative complex back wounds that
necessitated muscle flap coverage included the involvement of instrumentation
(77.6%), a previous history of radiotherapy (33.2%), smoking (20.6%), and
diabetes mellitus (17.2%). In patients with instrumentation, prophylactic
coverage of the wound with a well-vascularized flap was shown to result in a
lower incidence of wound complications. One study showed a statistically
significant decrease in complications compared with patients where prophylactic
coverage was not performed (20% vs 45%). The indications for flap coverage after
onset of wound complications included hardware exposure, wound infection,
dehiscence, seroma, and hematoma. Flap coverage was shown to decrease the number
of surgical debridements needed and also salvage hardware, with the rate of
hardware removal after flap coverage ranging from 0% to 41.9% in 4 studies.
CONCLUSIONS Prophylactic coverage with flaps in high-risk patients undergoing
spine surgery reduces complications, while therapeutic coverage following wound
complications allows the salvage of hardware in the majority of patients.
PMID- 26424342
TI - Perioperative morbidity and mortality after lumbar trauma in the elderly.
AB - OBJECT Traumatic fractures of the thoracolumbar spine are common injuries,
accounting for approximately 90% of all spinal trauma. Lumbar spine trauma in the
elderly is a growing public health problem with relatively little evidence to
guide clinical management. The authors sought to characterize the complications,
morbidity, and mortality associated with surgical and nonsurgical management in
elderly patients with traumatic fractures of the lumbar spine. METHODS Using the
National Sample Program of the National Trauma Data Bank, the authors performed a
retrospective analysis of patients >= 55 years of age who had traumatic fracture
to the lumbar spine. This group was divided into middle-aged (55-69 years) and
elderly (>= 70 years) cohorts. Cohorts were subdivided into nonoperative,
vertebroplasty or kyphoplasty, noninstrumented surgery, and instrumented surgery.
Univariate and multivariable analyses were used to characterize and identify
predictors of medical and surgical complications, mortality, hospital length of
stay, ICU length of stay, number of days on ventilator, and hospital discharge in
each subgroup. Adjusted odds ratios, mean differences, and associated 95% CIs
were reported. Statistical significance was assessed at p < 0.05, and the
Bonferroni correction for multiple comparisons was applied for each outcome
analysis. RESULTS Between 2003 and 2012, 22,835 people met the inclusion
criteria, which represents 94,103 incidents nationally. Analyses revealed a
similar medical and surgical complication profile between age groups. The most
prevalent medical complications were pneumonia (7.0%), acute respiratory distress
syndrome (3.6%), and deep venous thrombosis (3%). Surgical site infections
occurred in 6.3% of cases. Instrumented surgery was associated with the highest
odds of each complication (p < 0.001). The inpatient mortality rate was 6.8% for
all subjects. Multivariable analyses demonstrated that age >= 70 years was an
independent predictor of mortality (OR 3.16, 95% CI 2.77-3.60), whereas
instrumented surgery (multivariable OR 0.38, 95% CI 0.28-0.52) and vertebroplasty
or kyphoplasty (OR 0.27, 95% CI 0.17-0.45) were associated with decreased odds of
death. In surviving patients, both older age (OR 0.32, 95% CI 0.30-0.34) and
instrumented fusion (OR 0.37, 95% CI 0.33-0.41) were associated with decreased
odds of discharge to home. CONCLUSIONS The present study confirms that lumbar
surgery in the elderly is associated with increased morbidity. In particular,
instrumented fusion is associated with periprocedural complications, prolonged
hospitalization, and a decreased likelihood of being discharged home. However,
fusion surgery is also associated with reduced mortality. Age alone should not be
an exclusionary factor in identifying surgical candidates for instrumented lumbar
spinal fusion. Future studies are needed to confirm these findings.
PMID- 26424343
TI - The safety profile of lumbar spinal surgery in elderly patients 85 years and
older.
AB - OBJECT The aging of the population will require that surgeons increasingly
consider operating on elderly patients. Performing surgery safely in the elderly
will require an understanding of the factors that predict successful outcomes and
avoid complications. METHODS Records of patients 85 years and older undergoing
elective lumbar spinal surgery were retrospectively reviewed. Microdiscectomies
were excluded. Preexisting medical illnesses measured using the Charlson
Comorbidity Index (CCI), American Society of Anesthesiologists (ASA) Physical
Status class, age, and surgical parameters were analyzed as factors potentially
predictive of complications. Ambulatory function was rated on a 4-point scale.
RESULTS During the study 26 consecutive patients (mean age 87 years) with a mean
ASA class of 2.6 +/- 0.65 and CCI of 1.1 +/- 1.27 were enrolled. The average
number of levels treated was 2.17 +/- 1.23, and 73% underwent fusion. The mean
follow-up was 41.9 months with a minimum of 24 months, and all patients were
alive at last follow-up. Average blood loss was 142 +/- 184 ml, and the operative
time was 183.3 +/- 80.6 minutes. The mean number of levels treated was 2.17 +/-
1.13 (range 1-4). Ambulatory function improved significantly by 0.59 +/- 1.0
points. Five complications (19.2%) occurred in 4 patients, 2 major and 3 minor.
Four complications were temporary and 1 was permanent. Patient age, blood loss,
CCI score, ASA class, the number of levels treated, and fusion surgery were not
statistically associated with a complication. Operative time of longer than 180
minutes (p = 0.0134) was associated with complications. CONCLUSIONS Lumbar spine
surgery in patients 85 years and older can be accomplished safely if careful
attention is paid to preoperative selection. Prolonged operative times are
associated with a higher risk of complications.
PMID- 26424344
TI - Comparison of complication rates of minimally invasive transforaminal lumbar
interbody fusion and lateral lumbar interbody fusion: a systematic review of the
literature.
AB - OBJECT Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) and
lateral lumbar interbody fusion (LLIF) are 2 currently popular techniques for
lumbar arthrodesis. The authors compare the total risk of each procedure, along
with other important complication outcomes. METHODS This systematic review was
conducted according to the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) guidelines. Relevant studies (up to May 2015) that
reported complications of either MI-TLIF or LLIF were identified from a search in
the PubMed database. The primary outcome was overall risk of complication per
patient. Secondary outcomes included risks of sensory deficits, temporary
neurological deficit, permanent neurological deficit, intraoperative
complications, medical complications, wound complications, hardware failure,
subsidence, and reoperation. RESULTS Fifty-four studies were included for
analysis of MI-TLIF, and 42 studies were included for analysis of LLIF. Overall,
there were 9714 patients (5454 in the MI-TLIF group and 4260 in the LLIF group)
with 13,230 levels fused (6040 in the MI-TLIF group and 7190 in the LLIF group).
A total of 1045 complications in the MI-TLIF group and 1339 complications in the
LLIF group were reported. The total complication rate per patient was 19.2% in
the MI-TLIF group and 31.4% in the LLIF group (p < 0.0001). The rate of sensory
deficits and temporary neurological deficits, and permanent neurological deficits
was 20.16%, 2.22%, and 1.01% for MI-TLIF versus 27.08%, 9.40%, and 2.46% for
LLIF, respectively (p < 0.0001, p < 0.0001, p = 0.002, respectively). Rates of
intraoperative and wound complications were 3.57% and 1.63% for MI-TLIF compared
with 1.93% and 0.80% for LLIF, respectively (p = 0.0003 and p = 0.034,
respectively). No significant differences were noted for medical complications or
reoperation. CONCLUSIONS While there was a higher overall complication rate with
LLIF, MI-TLIF and LLIF both have acceptable complication profiles. LLIF had
higher rates of sensory as well as temporary and permanent neurological symptoms,
although rates of intraoperative and wound complications were less than MI-TLIF.
Larger, prospective comparative studies are needed to confirm these findings as
the current literature is of relative poor quality.
PMID- 26424345
TI - Morphometrics as a predictor of perioperative morbidity after lumbar spine
surgery.
AB - OBJECT Improved objective assessments of perioperative risk after spine surgery
are necessary to decrease postoperative morbidity and mortality rates.
Morphometric analysis has proven utility in predicting postoperative morbidity
and mortality in surgical disciplines. The aim of the present study was to
evaluate whether morphometrics can be applied to the cases of patients undergoing
lumbar spine surgery. METHODS The authors performed a retrospective review of the
perioperative course of 395 patients who underwent lumbar surgery at their
institution from 2013 to 2014. Preoperative risk factors such as age, diabetes,
smoking, coronary artery disease, and body mass index (BMI) were recorded.
Preoperative MRI was used to measure the psoas muscle area at the L-4 vertebra
and paraspinal muscle area at the T-12 vertebra. Primary outcomes included
unplanned return to the operating room, 30- and 90-day readmissions, surgical
site infection, wound dehiscence, new neurological deficit, deep vein thrombosis,
pulmonary embolism, myocardial infarction, urinary tract infection, urinary
retention, hospital-acquired pneumonia, stroke, and prolonged stay in the
intensive care unit. RESULTS The overall rate of adverse events was 30%, the most
common event being urinary retention (12%). Greater age (p = 0.015) and tobacco
usage (p = 0.026) were both significantly associated with complications for all
patients, while diabetes, coronary artery disease, and high BMI were not. No
surgery-related characteristics were associated with postoperative morbidity,
including whether surgery required instrumentation, whether it was a revision, or
the number of vertebral levels treated. Using multivariate regression analysis,
male and female patients with the lowest psoas tertile had an OR of 1.70 (95% CI
1.04-2.79, p = 0.035) for having postoperative complications. Male patients in
the lowest psoas tertile had an OR of 2.42 (95% CI 1.17-5.01, p = 0.016) for
having a postoperative complication. The paraspinal muscle groups did not provide
any significant data for postoperative morbidity, even after multivariate
analysis. CONCLUSIONS The morphometric measurement of psoas muscle size may be a
sensitive predictive tool compared with other risk factors for perioperative
morbidity in male patients undergoing lumbar surgery.
PMID- 26424346
TI - Lumbar microdiscectomy complication rates: a systematic review and meta-analysis.
AB - OBJECT Lumbar microdiscectomy and its various minimally invasive surgical
techniques are seeing increasing popularity, but a systematic review of their
associated complications has yet to be performed. The authors sought to identify
all prospective clinical studies reporting complications associated with lumbar
open microdiscectomy, microendoscopic discectomy (MED), and percutaneous
microdiscectomy. METHODS The authors conducted MEDLINE, Scopus, Web of Science,
and Embase database searches for randomized controlled trials and prospective
cohort studies reporting complications associated with open, microendoscopic, or
percutaneous lumbar microdiscectomy. Studies with fewer than 10 patients and
published before 1990 were excluded. Overall and interstudy median complication
rates were calculated for each surgical technique. The authors also performed a
meta-analysis of the reported complications to assess statistical significance
across the various surgical techniques. RESULTS Of 9504 articles retrieved from
the databases, 42 met inclusion criteria. Most studies screened were
retrospective case series, limiting the number of studies that could be included.
A total of 9 complication types were identified in the included studies, and
these were analyzed across each of the surgical techniques. The rates of any
complication across the included studies were 12.5%, 13.3%, and 10.8% for open,
MED, and percutaneous microdiscectomy, respectively. New or worsening
neurological deficit arose in 1.3%, 3.0%, and 1.6% of patients, while direct
nerve root injury occurred at rates of 2.6%, 0.9%, and 1.1%, respectively.
Hematoma was reported at rates of 0.5%, 1.2%, and 0.6%, respectively. Wound
complications (infection, dehiscence, orseroma) occurred at rates of 2.1%, 1.2%,
and 0.5%, respectively. The rates of recurrent disc complications were 4.4%,
3.1%, and 3.9%, while reoperation was indicated in 7.1%, 3.7%, and 10.2% of
operations, respectively. Meta-analysis calculations revealed a statistically
significant higher rate of intraoperative nerve root injury following
percutaneous procedures relative to MED. No other significant differences were
found. CONCLUSIONS This review highlights complication rates among various
microdiscectomy techniques, which likely reflect real-world practice and
conceptualization of complications among physicians. This investigation sets the
framework for further discussions regarding microdiscectomy options and their
associated complications during the informed consent process.
PMID- 26424347
TI - Thirty-day readmission rates in spine surgery: systematic review and meta
analysis.
AB - OBJECT The rate of 30-day readmissions is rapidly gaining significance as a
quality metric and is increasingly used to evaluate performance. An analysis of
the present 30-day readmission rate in the spine literature is needed to aid the
development of policies to decrease the frequency of readmissions. The authors
examine 2 questions: 1) What is the 30-day readmission rate as reported in the
spine literature? 2) What study factors impact the rate of 30-day readmissions?
METHODS This study was registered with Prospera (CRD42014015319), and 4
electronic databases (PubMed, Cochrane Library, Web of Science, and Google
Scholar) were searched for articles. A systematic review and meta-analysis was
performed to assess the current 30-day readmission rate in spine surgery.
Thirteen studies met inclusion criteria. The readmission rate as well as data
source, time from enrollment, sample size, demographics, procedure type and spine
level, risk factors for readmission, and causes of readmission were extrapolated
from each study. RESULTS The pooled 30-day readmission rate was 5.5% (95% CI 4.2%
7.4%). Studies from single institutions reported the highest 30-day readmission
rate at 6.6% (95% CI 3.8%-11.1%), while multicenter studies reported the lowest
at 4.7% (95% CI 2.3%-9.7%). Time from enrollment had no statistically significant
effect on the 30-day readmission rate. Studies including all spinal levels had a
higher 30-day readmission rate (6.1%, 95% CI 4.1%-8.9%) than exclusively lumbar
studies (4.6%, 95% CI 2.5%-8.2%); however, the difference between the 2 rates was
not statistically significant (p = 0.43). The most frequently reported risk
factors associated with an increased odds of 30-day readmission on multivariate
analysis were an American Society of Anesthesiology score of 4+, operative
duration, and Medicare/Medicaid insurance. The most common cause of readmission
was wound complication (39.3%). CONCLUSIONS The 30-day readmission rate following
spinal surgery is between 4.2% and 7.4%. The range, rather than the exact result,
should be considered given the significant heterogeneity among studies, which
indicates that there are factors such as demographics, procedure types, and
individual institutional factors that are important and affect this outcome
variable. The pooled analysis of risk factors and causes of readmission is
limited by the lack of reporting in most of the spine literature.
PMID- 26424348
TI - Unintended durotomy in lumbar degenerative spinal surgery: a 10-year systematic
review of the literature.
AB - OBJECT Unintended durotomy is a common occurrence during lumbar spinal surgery,
particularly in surgery for degenerative spinal conditions, with the reported
incidence rate ranging from 0.3% to 35%. The authors performed a systematic
literature review on unintended lumbar spine durotomy, specifically aiming to
identify the incidence of durotomy during spinal surgery for lumbar degenerative
conditions. In addition, the authors analyzed the incidence of durotomy when
minimally invasive surgical approaches were used as compared with that following
a traditional midline open approach. METHODS A MEDLINE search using the term
"lumbar durotomy" (under the 2015 medical subject heading [MeSH] "cerebrospinal
fluid leak") was conducted on May 13, 2015, for English-language medical
literature published in the period from January 1, 2005, to May 13, 2015. The
resulting papers were categorized into 3 groups: 1) those that evaluated
unintended durotomy rates during open-approach lumbar spinal surgery, 2) those
that evaluated unintended durotomy rates during minimally invasive spine surgery
(MISS), and 3) those that evaluated durotomy rates in comparable cohorts
undergoing MISS versus open-approach lumbar procedures for similar lumbar
pathology. RESULTS The MEDLINE search yielded 116 results. A review of titles
produced 22 potentially relevant studies that described open surgical procedures.
After a thorough review of individual papers, 19 studies (comprising 15,965
patients) pertaining to durotomy rates during open-approach lumbar surgery were
included for analysis. Using the Oxford Centre for Evidence-Based Medicine (CEBM)
ranking criteria, there were 7 Level 3 prospective studies and 12 Level 4
retrospective studies. In addition, the authors also included 6 studies (with a
total of 1334 patients) that detailed rates of durotomy during minimally invasive
surgery for lumbar degenerative disease. In the MISS analysis, there were 2
prospective and 4 retrospective studies. Finally, the authors included 5 studies
(with a total of 1364 patients) that directly compared durotomy rates during open
approach versus minimally invasive procedures. Studies of open-approach surgery
for lumbar degenerative disease reported a total of 1031 durotomies across all
procedures, for an overall durotomy rate of 8.11% (range 2%-20%). Prospectively
designed studies reported a higher rate of durotomy than retrospective studies
(9.57% vs 4.32%, p = 0.05). Selected MISS studies reported a total of 93
durotomies for a combined durotomy rate of 6.78%. In studies of matched cohorts
comparing open-approach surgery with MISS, the durotomy rates were 7.20% (34
durotomies) and 7.02% (68), respectively, which were not significantly different.
CONCLUSIONS Spinal surgery for lumbar degenerative disease carries a significant
rate of unintended durotomy, regardless of the surgical approach selected by the
surgeon. Interpretation of unintended durotomy rates for lumbar surgery is
limited by a lack of prospective and cohort-matched controlled studies.
PMID- 26424349
TI - Iatrogenic spondylolisthesis following laminectomy for degenerative lumbar
stenosis: systematic review and current concepts.
AB - OBJECT Decompression without fusion for degenerative lumbar stenosis is an
effective treatment for both the pain and disability of neurogenic claudication.
Iatrogenic instability following decompression may require further intervention
to stabilize the spine. The authors review the incidence of postsurgical
instability following lumbar decompression, and assess the impact of surgical
technique as well as study design on the incidence of instability. METHODS A
comprehensive literature search was performed to identify surgical cohorts of
patients with degenerative lumbar stenosis, with and without preexisting
spondylolisthesis, who were treated with laminectomy or minimally invasive
decompression without fusion. Data on patient characteristics, surgical
indications and techniques, clinical and radiographic outcomes, and reoperation
rates were collected and analyzed. RESULTS A systematic review of 24 studies
involving 2496 patients was performed, assessing both open laminectomy and
minimally invasive bilateral canal enlargement. Postoperative pain and functional
outcomes were similar across the various studies, and postoperative radiographie
instability was seen in 5.5% of patients. Instability was seen more frequently in
patients with preexisting spondylolisthesis (12.6%) and in those treated with
open laminectomy (12%). Reoperation for instability was required in 1.8% of all
patients, and was higher for patients with preoperative spondylolisthesis (9.3%)
and for those treated with open laminectomy (4.1%). CONCLUSIONS Instability
following lumbar decompression is a common occurrence. This is particularly true
if decompression alone is selected as a surgical approach in patients with
established spondylolisthesis. This complication may occur less commonly with the
use of minimally invasive techniques; however, larger prospective cohort studies
are necessary to more thoroughly explore these findings.
PMID- 26424350
TI - Heart drug pushes outcome-based pricing plans.
PMID- 26424351
TI - Cancer drug developers counteract kinase gatekeeper mutations.
PMID- 26424352
TI - FDA approves ultra-orphan drug on a 4-patient trial.
PMID- 26424353
TI - FDA approves female sexual dysfunction drug.
PMID- 26424354
TI - Off-label targeted cancer drugs fail in first randomized trial.
PMID- 26424355
TI - Infectious diseases: Vaccine for Middle East respiratory syndrome.
PMID- 26424356
TI - Cancer: Small-molecule FGF trap shrinks tumours.
PMID- 26424360
TI - Electric-field-induced local and mesoscale structural changes in polycrystalline
dielectrics and ferroelectrics.
AB - The atomic-scale response of dielectrics/ferroelectrics to electric fields is
central to their functionality. Here we introduce an in situ characterization
method that reveals changes in the local atomic structure in polycrystalline
materials under fields. The method employs atomic pair distribution functions
(PDFs), determined from X-ray total scattering that depends on orientation
relative to the applied field, to probe structural changes over length scales
from sub-Angstrom to several nanometres. The PDF is sensitive to local ionic
displacements and their short-range order, a key uniqueness relative to other
techniques. The method is applied to representative ferroelectrics, BaTiO3 and
Na1/2Bi1/2TiO3, and dielectric SrTiO3. For Na1/2Bi1/2TiO3, the results reveal an
abrupt field-induced monoclinic to rhombohedral phase transition, accompanied by
ordering of the local Bi displacements and reorientation of the nanoscale
ferroelectric domains. For BaTiO3 and SrTiO3, the local/nanoscale structural
changes observed in the PDFs are dominated by piezoelectric lattice strain and
ionic polarizability, respectively.
PMID- 26424361
TI - Authors' reply to Bonten.
PMID- 26424362
TI - Coping with Work-Related Stress through Guided Imagery and Music (GIM):
Randomized Controlled Trial.
AB - BACKGROUND: Long-term stress-related sick leave constitutes a serious health
threat and an economic burden on both the single worker and the society.
Effective interventions for the rehabilitation and facilitation of return to work
are needed. OBJECTIVE: The aim of the study was to examine the effects of Guided
Imagery and Music (GIM), a psychotherapy intervention including relaxation, music
listening, and imagery, on biopsychosocial measures of work-related stress.
METHODS: Twenty Danish workers on sick leave were randomized to music therapy
versus wait-list control. Data collection was carried out at an occupational
health ward in the period 2008-2010. Changes in salivary cortisol, testosterone,
and melatonin were explored, and self-reported data on psychological stress
symptoms (perceived stress, mood disturbance, sleep quality, physical distress
symptoms, work readiness, well-being, anxiety, depression, immediate stress) were
collected. Data regarding sick leave situation and job return were collected from
participants throughout the study. RESULTS: Significant beneficial effects of GIM
compared to wait-list after nine weeks with large effect sizes were found in well
being, mood disturbance, and physical distress, and in cortisol concentrations
with a medium effect size. A comparison between early and late intervention as
related to the onset of sick leave showed faster job return and significantly
improved perceived stress, well-being, mood disturbance, depression, anxiety, and
physical distress symptoms in favor of early intervention. In the whole sample,
83% of the participants had returned to work at nine weeks' follow-up.
CONCLUSIONS: The results indicate that GIM is a promising treatment for work
related chronic stress, and further studies are recommended.
PMID- 26424364
TI - A heuristic approach to determine an appropriate number of topics in topic
modeling.
AB - BACKGROUND: Topic modelling is an active research field in machine learning.
While mainly used to build models from unstructured textual data, it offers an
effective means of data mining where samples represent documents, and different
biological endpoints or omics data represent words. Latent Dirichlet Allocation
(LDA) is the most commonly used topic modelling method across a wide number of
technical fields. However, model development can be arduous and tedious, and
requires burdensome and systematic sensitivity studies in order to find the best
set of model parameters. Often, time-consuming subjective evaluations are needed
to compare models. Currently, research has yielded no easy way to choose the
proper number of topics in a model beyond a major iterative approach. METHODS AND
RESULTS: Based on analysis of variation of statistical perplexity during topic
modelling, a heuristic approach is proposed in this study to estimate the most
appropriate number of topics. Specifically, the rate of perplexity change (RPC)
as a function of numbers of topics is proposed as a suitable selector. We test
the stability and effectiveness of the proposed method for three markedly
different types of grounded-truth datasets: Salmonella next generation
sequencing, pharmacological side effects, and textual abstracts on computational
biology and bioinformatics (TCBB) from PubMed. CONCLUSION: The proposed RPC-based
method is demonstrated to choose the best number of topics in three numerical
experiments of widely different data types, and for databases of very different
sizes. The work required was markedly less arduous than if full systematic
sensitivity studies had been carried out with number of topics as a parameter. We
understand that additional investigation is needed to substantiate the method's
theoretical basis, and to establish its generalizability in terms of dataset
characteristics.
PMID- 26424363
TI - Health economic modeling of the potential cost saving effects of Neurally
Adjusted Ventilator Assist.
AB - OBJECTIVES: Asynchrony between patient and ventilator breaths is associated with
increased duration of mechanical ventilation (MV). Neurally Adjusted Ventilatory
Assist (NAVA) controls MV through an esophageal reading of diaphragm electrical
activity via a nasogastric tube mounted with electrode rings. NAVA has been shown
to decrease asynchrony in comparison to pressure support ventilation (PSV). The
objective of this study was to conduct a health economic evaluation of NAVA
compared with PSV. METHODS: We developed a model based on an indirect link
between improved synchrony with NAVA versus PSV and fewer days spent on MV in
synchronous patients. Unit costs for MV were obtained from the Swedish intensive
care unit register, and used in the model along with NAVA-specific costs. The
importance of each parameter (proportion of asynchronous patients, costs, and
average MV duration) for the overall results was evaluated through sensitivity
analyses. RESULTS: Base case results showed that 21% of patients ventilated with
NAVA were asynchronous versus 52% of patients receiving PSV. This equals an
absolute difference of 31% and an average of 1.7 days less on MV and a total cost
saving of US$7886 (including NAVA catheter costs). A breakeven analysis suggested
that NAVA was cost effective compared with PSV given an absolute difference in
the proportion of asynchronous patients greater than 2.5% (49.5% versus 52%
asynchronous patients with NAVA and PSV, respectively). The base case results
were stable to changes in parameters, such as difference in asynchrony, duration
of ventilation and daily intensive care unit costs. CONCLUSION: This study showed
economically favorable results for NAVA versus PSV. Our results show that only a
minor decrease in the proportion of asynchronous patients with NAVA is needed for
investments to pay off and generate savings. Future studies need to confirm this
result by directly relating improved synchrony to the number of days on MV.
PMID- 26424365
TI - Molecular Insights into Aqueous NaCl Electrolytes Confined within Vertically
oriented Graphenes.
AB - Vertically-oriented graphenes (VGs) are promising active materials for electric
double layer capacitors (EDLCs) due to their unique morphological and structural
features. This study, for the first time, reports the molecular dynamics (MD)
simulations on aqueous NaCl electrolytes confined within VG channels with
different surface charge densities and channel widths. Simulation results show
that the accessibility of ions and the structure of EDLCs are determined by the
ion type/size, surface charging, and VG channel width. For relatively narrow VG
channels with the same width, the threshold charge density (to compensate the
energy penalty for shedding hydration shell) and the dehydration rate of Cl(-)
ions are larger than those of Na(+) ions. To achieve the highest ion
concentration coefficient, the effective VG channel width should be between the
crystal and hydration diameters of the ions. The results are further quantified
and elucidated by calculating the electrolyte density profiles. The molecular
insights obtained in the current work are useful in guiding the design and
fabrication of VGs for advancing their EDLC applications.
PMID- 26424366
TI - Emergency readmissions are highest in patients discharged at weekends.
PMID- 26424367
TI - Oncological emergencies associated with gastrointestinal tumors.
AB - Oncological emergencies are defined as acute life-threatening conditions in
cancer patients either as a result of the malignancy or as a result of its
treatment. In this review, we focus on oncological emergencies associated with
gastrointestinal tumors. They can be categorized by their system of origin as
hematologic, neurologic or metabolic. Furthermore, we discuss mechanical
emergencies such as intestinal obstruction and vena cava superior syndrome as
well as acute gastrointestinal bleeding and pulmonary embolism. The patients'
performance status as well as prognosis are essential during decision making for
optimal treatment.
PMID- 26424369
TI - Focus on the surgical approach to transcatheter aortic valve implantation:
Complications, outcome, and preoperative risk adjustment.
AB - OBJECTIVE: Perioperative complications in patients undergoing transcatheter
aortic valve implantation remain a major issue affecting outcome. Because
preoperative risk adjustment remains challenging and a valid scoring system is
missing, we sought to determine the incidence of peri- and postprocedural
complications of transapical (TA) or transaortic (TAO) access to define the
influence of specific complications on early safety, 30-day mortality, and 1-year
survival. Furthermore, we aimed to develop a risk-stratification model to allow
an estimation of the perioperative risk and the 1-year survival rate, based on
the individual preoperative condition of each patient. METHODS: We performed an
outcome analysis of 230 consecutive patients who underwent aortic valve
implantation via transapical or transaortic access between 2008 and 2012, with
regard to Valve Academic Research Consortium II criteria, including univariate
and multivariable regression analysis, to develop a risk-stratification model.
RESULTS: Thirty-day mortality was 12.7%. Estimated 1-year survival was 0.69 (95%
confidence interval [CI], 0.631-0.757), and 3-year survival was 0.554 (95% CI,
0.474-0.634). Univariate logistic regression analysis revealed a significant
influence on 30-day mortality in case of life-threatening bleeding (16.1-fold),
abdominal complications (8.5-fold), and acute kidney injury (3.2-fold). Pacemaker
implantation (odds ratio, 1.55; 95% CI, 0.42-5.81; P = .512) was not a
significant predictor. Concerning use of intraprocedural hemodynamic bridging
therapy via cardiopulmonary bypass (CPB), Cox regression analysis revealed no
significant survival difference after 1 year. A preoperative risk-stratification
model for 1-year survival revealed that a logistic European System for Cardiac
Operative Risk Evaluation score >20%, preoperative existing coronary artery
disease, and prior myocardial infarction appeared to be significant predictors
for diminished survival. CONCLUSIONS: Concerning intraprocedural complications,
CPB support for hemodynamic stabilization is a safe treatment option. Therefore,
the heart team approach with CPB standby represents a life-saving option.
Attention should also be drawn to specialized and individual postoperative care,
because nonprocedure-specific complications clearly affect postoperative short-
and long-term outcome. In addition, the risk-stratification model might
facilitate preoperative decision making.
PMID- 26424368
TI - Determinants of the t(14;18) translocation and their role in t(14;18)-positive
follicular lymphoma.
AB - PURPOSE: The strong association between t(14;18) translocation and follicular
lymphoma (FL) is well known. However, the determinants of this chromosomal
aberration and their role in t(14;18) associated FL remain to be established.
METHODS: t(14;18) frequency within the B cell lymphoma 2 major breakpoint region
was determined for 135 incident FL cases and 251 healthy controls as part of a
nested case-control study within the European Prospective Investigation into
Cancer cohort. Quantitative real-time PCR was performed in DNA extracted from
blood samples taken at recruitment. The relationship between prevalence and
frequency of the translocation with baseline anthropometric, lifestyle, and
dietary factors in cases and controls was determined. Unconditional logistic
regression was used to explore whether the risk of FL associated with these
factors differed in t(14;18)(+) as compared to t(14;18)(-) cases. RESULTS: Among
incident FL cases, educational level (chi(2) p = 0.021) and height (chi(2) p =
0.025) were positively associated with t(14;18) prevalence, and cases with high
frequencies [t(14;18)(HF)] were significantly taller (t test p value = 0.006).
These findings were not replicated in the control population, although there were
a number of significant associations with dietary variables. Further analyses
revealed that height was a significant risk factor for t(14;18)(+) FL [OR 6.31
(95% CI 2.11, 18.9) in the tallest versus the shortest quartile], but not
t(14;18)(-) cases. CONCLUSIONS: These findings suggest a potential role for
lifestyle factors in the prevalence and frequency of the t(14;18) translocation.
The observation that the etiology of FL may differ by t(14;18) status,
particularly with regard to height, supports the subdivision of FL by
translocation status.
PMID- 26424370
TI - Efforts to improve bypass graft patency have not been "in vein".
PMID- 26424371
TI - Internal thoracic artery grafting in the elderly and the challenge to
conventional wisdom.
PMID- 26424372
TI - Neopulmonary reconstruction: Operam do.
PMID- 26424373
TI - Septal myectomy in context: Clinical acumen and procedural expertise.
PMID- 26424374
TI - On biostatisticians and their role in cardiothoracic surgery research.
PMID- 26424375
TI - Biostatisticians and the future of cardiovascular research.
PMID- 26424376
TI - JBP485 promotes corneal epithelial wound healing.
AB - Proper wound healing is vital for maintenance of corneal integrity and
transparency. Corneal epithelial damage is one of the most frequently observed
ocular disorders. Because clinical options are limited, further novel treatments
are needed to improve clinical outcomes for this type of disease. In the present
study, it was found that placental extract-derived dipeptide (JBP485)
significantly increased the proliferation and migration of corneal epithelial
cells (CECs). Moreover, JBP485 accelerated corneal epithelial wound healing in
vivo without inflammation and neovascularization and was found to be effective
for the treatment of corneal damage. These data indicate that JBP485 efficiently
activates the viability of CECs and has potential as a novel treatment for
various kinds of corneal epithelial disease.
PMID- 26424378
TI - Paradoxical (rapid eye movement) sleep-on neurons in the laterodorsal pontine
tegmentum in mice.
AB - A total of 211 neurons that discharged at the highest rate during sleep (sleep
active neurons) were recorded in non-anesthetized, head-restrained mice during
the complete wake-sleep cycle in, and around, the laterodorsal (LDT) and
sublaterodorsal (SubLDT) tegmental nuclei, which contain both cholinergic and non
cholinergic neurons. For the first time in mice, I reveal the presence, mainly in
the SubLDT, of sleep-specific neurons displaying sustained tonic discharge either
(i) just prior to, and during, paradoxical sleep (PS) (PS-on neurons) or (ii)
during both slow-wave sleep (SWS) and PS (SWS/PS-on neurons). Both the PS-on and
SWS/PS-on neurons showed either a low (< 10 Hz) or high (? 10 Hz) rate of
spontaneous firing and exhibited a biphasic narrow or medium-to-broad action
potential, a characteristic of non-cholinergic neurons. At the transition from
SWS to waking (W), the PS-on and SWS/PS-on neurons simultaneously ceased firing
shortly before the onset of W, whereas, at the transition from W to SWS, only the
SWS/PS-on neurons fired shortly after the onset of sleep. At the transition from
SWS to PS, only the PS-on neurons exhibited a significant increase in discharge
rate before PS onset, while, at the transition from PS to W, the SWS/PS-on
neurons, then the PS-on neurons, displayed a significant decrease in the
discharge rate before the end of PS. The SWS/PS-on neurons were more sensitive to
the change in the electroencephalogram (EEG) than the PS-on neurons, as, during a
PS episode, the slightest interruption of rhythmic theta activity resulted in
cessation of discharge of the SWS/PS-on neurons. These findings support the view
that, in the mouse SubLDT, PS-on neurons play an important role in the induction,
maintenance, and cessation of PS, while SWS/PS-on neurons play a role in the
maintenance of the PS state in particular and the sleep state in general.
PMID- 26424377
TI - Comparative aspects of immunity and vaccination in human and bovine
trichomoniasis: a review.
AB - Trichomonas vaginalis and Tritrichomonas foetus are important extracellular
protozoans that cause, respectively, human and bovine venereal diseases.
Trichomonads are extracellular parasites that primarily inhabit the genital
tracts of the mammalian hosts where they overcome the mucus barrier and
parasitize mucosa by contact-dependent or contact-independent cytotoxicity.
Transient immunity is usually achieved by the host after clinical infection. At
present, vaccination in cattle reduces infection rates and reproductive wastage
in affected herds. After vaccination, immunoglobulin G (IgG) levels increase in
systemic circulation while immunoglobulin A (IgA) levels rise in the vagina. Only
moderate protection is conferred by means of vaccination. Future vaccine
development strategies are needed for cattle to enhance the antigenic component
or use adjuvant that strongly activates the innate immune response to produce
safe and potent vaccines. This paper reviews the current knowledge of the
immunology of trichomoniasis infection and the challenges and potential of
vaccines in the control of the infection in human and bovine trichomoniasis.
PMID- 26424379
TI - Effects of facial color on the subliminal processing of fearful faces.
AB - Recent studies have suggested that both configural information, such as face
shape, and surface information is important for face perception. In particular,
facial color is sufficiently suggestive of emotional states, as in the phrases:
"flushed with anger" and "pale with fear." However, few studies have examined the
relationship between facial color and emotional expression. On the other hand,
event-related potential (ERP) studies have shown that emotional expressions, such
as fear, are processed unconsciously. In this study, we examined how facial color
modulated the supraliminal and subliminal processing of fearful faces. We
recorded electroencephalograms while participants performed a facial emotion
identification task involving masked target faces exhibiting facial expressions
(fearful or neutral) and colors (natural or bluish). The results indicated that
there was a significant interaction between facial expression and color for the
latency of the N170 component. Subsequent analyses revealed that the bluish
colored faces increased the latency effect of facial expressions compared to the
natural-colored faces, indicating that the bluish color modulated the processing
of fearful expressions. We conclude that the unconscious processing of fearful
faces is affected by facial color.
PMID- 26424380
TI - Distribution of serotonin receptor 5-HT6 mRNA in rat neuronal subpopulations: A
double in situ hybridization study.
AB - The 5-HT6 receptor (5-HT6R) is almost exclusively expressed in the brain and has
emerged as a promising target for cognitive disorders, including Alzheimer's
disease. In the present study, we have determined the cell types on which the 5
HT6R is expressed by colocalizing 5-HT6R mRNA with that of a range of neuronal
and interneuronal markers in the rat brain. Here, we show that 5-HT6R mRNA was
expressed at high levels in medium spiny neurons in caudate putamen and in
nucleus accumbens, as well as in the olfactory tubercle. Striatal 5-HT6R mRNA was
colocalized with both dopamine D1 and D2 receptor mRNA. 5-HT6R mRNA was
moderately expressed in the hippocampus and throughout cortical regions in
glutamatergic neurons coexpressing vGluT1. A subset of GAD67-positive GABAergic
interneurons (approximately 15%) expressed 5-HT6R mRNA in the cortex and
hippocampus, the majority of which belonged to the 5-HT3a receptor (5-HT3aR)
expressing subpopulation. In contrast, 5-HT6R mRNA was only expressed to a minor
extent in the parvalbumin and somatostatin subpopulations. A subset of calbindin-
and calretinin-positive GABAergic interneurons expressed 5-HT6R mRNA while only a
very minor fraction of VIP or NPY interneurons in forebrain structures expressed
5-HT6R mRNA. Serotonergic, dopaminergic or cholinergic neurons did not express 5
HT6R mRNA. These data indicate that the 5-HT6R is located on GABAergic and
glutamatergic principal neurons, and on a subset of interneurons mainly belonging
to the 5-HT3aR subgroup suggesting that the 5-HT6R is positioned to regulate the
balance between excitatory and inhibitory signaling in the brain. These data
provide new insights into the mechanisms of 5-HT6R signaling.
PMID- 26424382
TI - Phylogeography of the European sturgeon (Acipenser sturio): A critically
endangered species.
AB - The European sturgeon (Acipenser sturio) was once a common species throughout
Europe, but the sole remaining natural population presently inhabits the Gironde
Estuary in France (Atlantic coast). The species was classified as 'Critically
Endangered' in 1996, and the Gironde population is now on the verge of
extinction. In this setting, and for the first time, we present the past
phylogeographical features of this species throughout Europe along with an
assessment of its former genetic diversity. This study was based on a molecular
analysis (mtDNA CR sequencing) of 10 living specimens from the Gironde Estuary,
55 museum specimens that had been caught along 19th and 20th centuries, and 59
archaeological remains dating back to 260-5000years BP, from which mitochondrial
DNA was extracted and amplified. Although discontinuous, the produced data
provided a realistic image of the former structure of A. sturio in Europe.
Reconstruction of the phylogenetic trees and haplotypes network led to the
identification of several clades. The mitochondrial genetic diversity of this
species was found to be much greater at the core (Iberian Peninsula,
Mediterranean and Adriatic regions) than along the margins (Atlantic-Northern
Europe, Black Sea) of its range. A series of hypotheses on the dates and causes
of changes in the species' major structures are put forward on the basis of these
data. Finally, competition with A. oxyrinchus, a sibling species whose presence
in Northern Europe was recently reconsidered, is presented as a major factor in
the evolution of this species.
PMID- 26424383
TI - Late-Life Depression and Antidepressants.
PMID- 26424381
TI - Ontogeny of tight junction protein expression in the ovine cerebral cortex during
development.
AB - Tight junctions of the blood-brain barrier are composed of transmembrane and
associated cytoplasmic proteins. The transmembrane claudin proteins form the
primary seal between endothelial cells and junctional adhesion molecules (JAMs)
regulate tight junction formation. We have previously shown that claudin-1,
claudin-5, zonula occludens (ZO)-1, and ZO-2 exhibit differential developmental
regulation from 60% of gestation up to maturity in adult sheep. The purpose of
the current study was to examine developmental changes in claudin-3, -12, and JAM
A protein expression in cerebral cortices of fetuses at 60%, 80%, and 90%
gestation, and in newborn and adult sheep. We also examined correlations between
changes in endogenous cortisol levels and tight junction protein expression in
cerebral cortices of the fetuses. Claudin-3, -12 and JAM-A expressions were
determined by Western immunoblot. Claudin-3 and -12 were lower (P<0.01) at 60%,
80%, 90% and in newborns than in adults, and JAM-A was lower in adults than in
fetuses at 80% and 90% gestation. Claudin-3 expression demonstrated a direct
correlation with increasing plasma cortisol levels (r=0.60, n=15, P<0.02) in the
fetuses. We conclude that: claudin-3, -12 and JAM-A are expressed as early as 60%
of gestation in ovine cerebral cortices, exhibit differential developmental
regulation, and that increasing endogenous glucocorticoids modulate claudin-3
expression in the fetus.
PMID- 26424384
TI - Natural occurrence of pure nano-polycrystalline diamond from impact crater.
AB - Consolidated bodies of polycrystalline diamond with grain sizes less than 100 nm,
nano-polycrystalline diamond (NPD), has been experimentally produced by direct
conversion of graphite at high pressure and high temperature. NPD has superior
hardness, toughness and wear resistance to single-crystalline diamonds because of
its peculiar nano-textures, and has been successfully used for industrial and
scientific applications. Such sintered nanodiamonds have, however, not been found
in natural mantle diamonds. Here we identified natural pure NPD, which was
produced by a large meteoritic impact about 35 Ma ago in Russia. The impact
diamonds consist of well-sintered equigranular nanocrystals (5-50 nm), similar to
synthetic NPD, but with distinct [111] preferred orientation. They formed through
the martensitic transformation from single-crystal graphite. Stress-induced local
fragmentation of the source graphite and subsequent rapid transformation to
diamond in the limited time scale result in multiple diamond nucleation and
suppression of the overall grain growth, producing the unique nanocrystalline
texture of natural NPD. A huge amount of natural NPD is expected to be present in
the Popigai crater, which is potentially important for applications as novel
ultra-hard material.
PMID- 26424385
TI - Cryptosporidiosis outbreak in visitors of a UK industry-compliant petting farm
caused by a rare Cryptosporidium parvum subtype: a case-control study.
AB - A case-control study was conducted to investigate an outbreak of 46 cases of
cryptosporidiosis in visitors to a petting farm in England. Details of exposures
on the farm were collected for 38 cases and 39 controls, recruited through
snowball sampling. Multivariable logistic regression identified that cases were
5.5 times more likely than controls to have eaten without washing their hands
[95% confidence interval (CI) 1.51-19.9, P = 0.01] and 10 times less likely to
report being informed of risk of infection on arrival (odds ratio 0.10, 95% CI
0.01-0.71, P = 0.02). An uncommon Cryptosporidium parvum gp60 subtype
(IIaA19G1R1) was identified in a lamb faecal sample and all subtyped cases (n =
22). We conclude that lack of verbal advice and non-compliance with hand washing
are significantly associated with a risk of cryptosporidiosis on open farms.
These findings highlight the public health importance of effectively
communicating risk to petting farm visitors in order to prevent future outbreaks
of zoonotic infections.
PMID- 26424386
TI - To Bleed or Not to Bleed: That is the Question. The Side Effects of Apixaban.
AB - Apixaban is a new oral anticoagulant (NOACs: Novel Oral Anticoagulant), like
dabigatran, rivaroxaban, and edoxaban. All of them are prescribed to patients
with non valvular atrial fibrillation or venous thromboembolism, to replace
warfarin, because of the lower probability of bleeding, however they can cause
bleeding by themselves. Bleeding is an adverse event in patients taking
anticoagulants. It is associated with a significant increase of morbidity and
risk of death. However, these drugs should be used only for the time when
anticoagulation is strictly required, especially when used for preventing deep
vein thrombosis. Prolonged use increases the risk of bleeding. In the ARISTOTLE
Trial Apixaban, compared with warfarin, was associated with a lower rate of
intracranial hemorrhages and less adverse consequences following extracranial
hemorrhage. Many physicians still have limited experience with new oral
anticoagulants and about bleeding risk managment. We reviewed the available
literature on extracranial and intracranial bleeding concerning apixaban.
PMID- 26424387
TI - Stress Hormone-Mediated DNA Damage Response--Implications for Cellular Senescence
and Tumour Progression.
AB - When DNA damage occurs, cells stop the cell cycle and DNA repair can take place.
However, if DNA damage exceeds DNA repair capacities, cells undergo either
apoptosis or senescence. These mechanisms preclude the proliferation of cells
with heavily damaged DNA, thus protecting the organism against tumour
development. When individuals are exposed to stress, the hypothalamic-pituitary
adrenal (HPA) axis and the sympathetic- adrenal-medullary (SAM) system can be
activated leading to secretion of corticosteroids and catecholamines,
respectively. The influences of these stress-related hormones have been proposed
to promote cellular senescence. But paradoxically, chronic stimulation of the HPA
axis is associated with higher risk of developing cancer. Focusing on the DNA
damage response pathway, this review discusses whether stress hormones induce
senescence or tumour progression or both and presents historical and recent data
that might help resolve some of these controversies.
PMID- 26424388
TI - Polysaccharide based Copolymers as Supramolecular Systems in Biomedical
Applications.
AB - Polysaccharides are natural polymers, obtained from a large variety of sources
ranging from fungi to more complex organisms such as birds and whales. Their use
for pharmaceutical and biomedical applications has been the subject of numerous
researches by the world's academia. Polysaccharide chemical/physical
modifications leading to graft copolymers are discussed in this review, focusing
on those nanosystems that are potential candidates for drug delivery
applications. Therefore, this review focuses on the biomedical application of
polysaccharide based copolymers, particularly as nanocarriers. Copolymer of
polysaccharides such as alginate, cellulose, chitosan, dextran, guar, hyaluronic
acid, pullulan and starch as drug delivery nanocarriers will be discussed.
PMID- 26424389
TI - Metallothionein as a Scavenger of Free Radicals - New Cardioprotective
Therapeutic Agent or Initiator of Tumor Chemoresistance?
AB - Cardiotoxicity is a serious complication of anticancer therapy by anthracycline
antibiotics. Except for intercalation into DNA/RNA structure, inhibition of DNA
topoisomerase and histone eviction from chromatin, the main mechanism of their
action is iron-mediated formation of various forms of free radicals, which leads
to irreversible damage to cancer cells. The most serious adverse effect of
anthracyclines is, thus, cardiomyopathy leading to congestive heart failure,
which is caused by the same mechanisms. Here, we briefly summarize the basic
types of free radicals formed by anthracyclines and the main processes how to
scavenge them. From these, the main attention is paid to metallothioneins. These
low-molecular cysteine-rich proteins are introduced and their functions and
properties are reviewed. Further, their role in detoxification of metals and
drugs is discussed. Based on these beneficial roles, their use as a new
therapeutic agent against oxidative stress and for cardioprotection is critically
evaluated with respect to their ability to increase chemoresistance against some
types of commonly used cytostatics.
PMID- 26424390
TI - From "An Enzyme Able to Destroy Penicillin" to Carbapenemases: 70 Years of Beta
lactamase Misbehaviour.
AB - As early as 1940, Abraham and Chain described "an enzyme able to destroy
penicillin". In the late 1940's, penicillin-resistant strains of Staphylococcus
aureus were found to be a clinical problem. They produced a penicillinase that
could hydrolyze the amide bond in the beta-lactam ring. Later, an enzyme mediated
by an R-factor was isolated from Enterobacteriaceae. Methicillin and
cephalosporins, both very poor substrates of the S. aureus enzyme, were found to
be sensitive to this new enzyme. Third generation cephalosporins appeared to
solve the problem, but further enzymes were selected that exhibited extended
spectra and could for instance hydrolyze cefotaxime and/or ceftazidime. The
discovery of carbapenems constituted a major advance for our antimicrobial
arsenal: they inactivated most of the essential penicillin binding proteins
effectively and escaped the activity of nearly all known -beta lactamases.
However, the metallo-beta-lactamases, which had not been recognised as a major
danger before 1990, were found to act as effective carbapenemases and started to
spread in a worrying way. Moreover, carbapenem-hydrolyzing enzymes were found in
each of the 3 classes of active-site serine beta-lactamases.
PMID- 26424391
TI - Sphingosine-1-Phosphate Receptors in the Central Nervous and Immune Systems.
AB - Sphingosine-1-phosphate receptor (S1PR) modulators have entered clinical practice
as immune-modulators for the treatment of multiple sclerosis (MS). Pharmacologic
modulation of S1PR expression on lymphocytes inhibits these cells capacity to
respond to the S1P gradient within regional lymph nodes (LNs) (and thymus) that
promotes their exit into peripheral circulation. The resultant peripheral blood
restricted lymphopenia is considered to underlie the capacity of S1PR modulators
to reduce new inflammatory lesion formation in MS in the absence of global immune
suppression. These modulators also regulate entry of selective lymphocyte
populations and dendritic cells (DCs) into LNs and modulate sphingosine-1
phosphate (S1P) cell signaling networks that govern the generation of specific
cell subsets within LNs. S1PR modulators that access the CNS can also have
functional effects within this compartment since S1PRs are expressed by cells
comprising the blood brain barrier (BBB) and by those within the parenchyma,
including neurons, astrocytes, oligodendrocytes and microglia. Absence of S1P1
receptor (S1PR1) on astrocytes reduces disease severity in experimental
autoimmune encephalomyelitis (EAE). Even under conditions that inhibit cell
responses to the natural ligand, S1PR modulators can continue to induce active
signaling responses; such responses may be relevant for promoting neuroprotection
and augmenting tissue repair within the CNS.
PMID- 26424392
TI - Alginate Bead-Encapsulated PEDF Induces Ectopic Bone Formation In Vivo in the
Absence of Co-Administered Mesenchymal Stem Cells.
AB - BACKGROUND: Bone defects can be severely debilitating and reduce quality of life.
Osteoregeneration can alleviate some of the complications in bony defects. For
therapeutic use in future, a single factor that can cause potent bone
regeneration is highly preferred as it will be more costeffective, any off-target
effects will be more easily monitored and potentially managed, and for ease of
administration which would lead to better patient compliance and satisfaction.
OBJECTIVE: We demonstrate that pigment epithelium-derived factor (PEDF), one such
factor that is known to be potent against angiogenesis, promotes
osteoblastogenesis in mesenchymal stem cells in vitro, but does not need co
encapsulation of cells in alginate bead scaffolds for osteogeneration in vivo.
RESULTS: Osteogenic differentiation by PEDF in vitro was confirmed with
immunoblotting and immunocytochemical staining for bone markers (alkaline
phosphatase, osteocalcin, osteopontin, collagen I), calcified mineral deposition,
and assay for alkaline phosphatase activity. PEDF-mediated bone formation in a
muscle pocket in vivo model was confirmed by microcomputed tomography (microCT),
histology (haematoxylin and eosin, Alcian blue staining), immunostaining for bone
markers and for collagen I-processing proteins (heat shock protein 47 and
membrane type I matrix metalloproteinase). CONCLUSION: PEDF therefore presents
itself as a promising biological for osteogeneration.
PMID- 26424393
TI - Gastrin-Releasing Peptide Receptor Targeting in Cancer Treatment: Emerging
Signaling Networks and Therapeutic Applications.
AB - Growth factors of the bombesin/gastrin releasing peptide (BN/GRP) family play a
critical role in proliferation and progression of malignancies. Inhibitors
targeting GRP signalling have been developed and tested as anticancer compounds
showing promising preclinical and early phase clinical results. In this review,
we will discuss the molecular signaling, expression and the functional role of
BN/GRP-GRPR in different cancer models and will focus on the available strategies
to target BN/GRP-GRPR in cancer treatment as well as in tumour diagnosis and
follow up.
PMID- 26424394
TI - New Pharmacological Approaches to the Prevention of Myocardial Ischemia-
Reperfusion Injury.
AB - BACKGROUND: Early reperfusion of the blocked vessel is critical to restore the
blood flow to the ischemic myocardium to salvage myocardial tissue and improve
clinical outcome. This reperfusion strategy after a period of ischemia, however,
may elicit further myocardial damage named myocardial reperfusion injury. The
manifestations of reperfusion injury include arrhythmias, myocardial stunning and
micro-vascular dysfunction, in addition to significant cardiomyocyte death. It is
suggested that an overproduction of reactive oxygen species, intracellular
calcium overload and inflammatory cell infiltration are the most important
features of myocardial ischemia-reperfusion injury. OBJECTIVE: In this review,
various pharmacological interventions to treat myocardial reperfusion injury
including the antioxidant flavonols, hydrogen sulfide, adenosine, opioids,
incretin-based therapies and cyclosporin A which targets the mitochondrial
permeability transition pore are discussed. CONCLUSION: The processes involved in
reperfusion injury might provide targets for improved outcomes after myocardial
infarction but thus far that aim has not been met in the clinic.
PMID- 26424395
TI - Effect of Genetic Polymorphisms (SNPs) in CHRNA7 Gene on Response to
Acetylcholinesterase Inhibitors (AChEI) in Patients with Alzheimer's Disease.
AB - BACKGROUND: Cholinergic transmission loss is one of the major features in
Alzheimer's Disease (AD). Acetylcholinesterase inhibitors (AChEI) are
moderately active in AD. alpha7nAChR (alpha-7 nicotinic acetylcholine receptor),
encoded by CHRNA7 (Nicotinic Cholinergic Receptor Alpha-7 gene), is involved in
the cholinergic neurotransmission and AD pathogenesis. alpha7nAChR is a putative
receptor of amyloid beta (Abeta). The complex alpha7nAChR-Abeta is found in
neuritic plaques and AD cortical neurons. In normal physiologic conditions,
alpha7nAChR-Abeta interaction leads to receptor activation. Genetic polymorphisms
(SNPs) of CHRNA7 and/or CHRFAM7A (fusion gene containing CHRNA7 partial
duplication) may be a possible susceptibility trait to dementia, potentially
useful to identify high risk or responder individuals. CHRFAM7A-2-bp deletion or
CHRNA7 SNPs (rs1514246, rs2337506, rs8027814) seem protective factors in
different forms of dementia including AD. OBJECTIVE: Correlation between(SNPs) of
CHRNA7 and/or CHRFAM7A and cholinesterase inhibitors in AD. METHODS: Literature
review. RESULTS: Among the leading AD therapeutics, Donepezil (DP) and
galantamine (AChEI) induce upregulation of alpha7nAChR protein levels, protecting
neurons from degeneration. Patients carrying rs8024987 (C/G) or rs6494223 (C/T)
respond better to AChEI. In the caucasic population rs6494223 TT subjects are 7
15% of the total. alpha7nAChR upregulation induced by DP is higher in lymphocytes
from TT subjects than in CC or CT as well as calcium uptake. CONCLUSION: The
correlation between genetic and functionality data may have an impact on several
aspects of disease presentation and therapy, helping in prediction pattern of AD
presentation and treatment efficacy. As a consequence it may lead to better
patients quality of life and longer periods of self- sufficiency. Moreover, it
may contribute to clarify AChEI mechanisms of action.
PMID- 26424396
TI - Withdrawn: The chemopreventive activity of beta-ionone involves modulation of
Rxralpha, Rarbeta and Coup-Tf1 expression in liver pre-neoplastic lesions in
rats.
AB - Withdrawn by the publisher.
PMID- 26424397
TI - The Contribution of Extracellular Nef to HIV-Induced Pathogenesis.
AB - Nef is an accessory protein expressed exclusively in primate lentiviruses. It is
devoid of enzymatic activities while interacting with several cell proteins as an
adaptor/scaffold protein. Intracellular functions of Nef largely account for many
pathogenic effects observed in AIDS disease. Nef, despite lacking known secretory
pathways, can be detected in plasma of HIV-1-infected patients at the
concentration varing from 5 to 10 ng/ml. Remarkably, the levels of Nef in plasma
of HIV patients do not correlate with viral load or number of CD4(+) T
lymphocytes, and persist during antiretroviral therapy. Here, we review
literature data describing how Nef can be transmitted from HIV-1- infected cells
to bystander ones, and the effects of extracellular Nef in different cell types.
Overall, large part of experimental evidences supports the idea that
extracellular Nef plays a relevant role in AIDS pathogenesis. Hence, efforts
focused on the identification of Nef-inhibiting drugs would be of relevance to
establish new therapeutic approaches supporting current antiretroviral therapies.
PMID- 26424399
TI - Nanosponge Carriers- An Archetype Swing in Cancer Therapy: A Comprehensive
Review.
AB - Nanotechnology and nanomedicines are emerging research meadows; which chiefly
focuses on creating and manipulating materials at a nanometer level for the
betterment in imaging, diagnosis and treatment of a range of diseases together
with cancer. Cyclodextrin-based nanosponges, anticipated as a new-fangled
nanosized delivery system, are ground-breaking hyper-crosslinked cyclodextrin
polymers nanostructured within a three-dimensional network. Nanosponges based
systems hold the potential of elevating the solubility, absorption, penetration,
bioavailability, in vivo stability, targeted as well as sustained delivery, and
therapeutic efficiency of numerous anticancer agents. The extension of
nanosponges based drug delivery systems is an exhilarating and demanding research
pasture, predominantly to overcome aforementioned problems allied to existing
anticancer formulations and for the further progressions in cancer therapies.
Nanosponges in cancer therapy, particularly cyclodextrin based nanosponges are
brought up in this review. By quoting diverse attempts made in pertinent
direction, efforts have been made to exemplify the characteristics, suitability
and versatility of cyclodextrin based nanosponges for their promising
applications in cancer treatment.
PMID- 26424400
TI - Possible Effects of Dietary Anthocyanins on Diabetes and Insulin Resistance.
AB - Diabetes is reaching epidemic proportions worldwide. Many dietary compounds have
been found to exert health beneficial effects against different pathologies
including diabetes. Most bioactive compounds have been identified in fruits and
vegetables and their mechanisms of action explored both in vitro and in vivo. In
particular, great interest has been given to polyphenols and especially to a
specific subset of molecules, i.e. anthocyanins. Several lines of evidence
suggest that anthocyanins have positive effects on human health by inducing a
number of biological activities. This review will give an overview on the
influence of dietary anthocyanins on preventing and managing type 2 diabetes. In
particular, in vitro and in vivo studies will be presented. The article also
reviews the potential clinical impact of the antidiabetic activity of
anthocyanins and outlines the major challenges of using anthocyanins for diabetes
treatment.
PMID- 26424401
TI - Decoding the Structural Basis For Carbapenem Hydrolysis By Class A beta
lactamases: Fishing For A Pharmacophore.
AB - Nowadays clinical therapy witnesses a challenging bacterial resistance limiting
the available armament of antibiotics. Over the decades strains resistant to all
antibiotics have been selected while medicinal chemists were not able to develop
agents capable of destroying them or to prevent their extension. In particular,
carbapenem-resistant Enterobacteriaceae (CRE), representing one of the most
common human pathogens, have been reported with increased frequency since their
first identification twenty years ago. The enterobacterial carbapenemases differ
from the extended spectrum beta-lactamases (ESBL) in their ability to hydrolyze
beta-lactams, cephalosporins and most importantly monobactams and carbapenems.
They are progressively spreading throughout the world, therefore leaving no
effective beta-lactam to cure bacterial infections. Several BLs-carbapenemase
Xray structures have been determined making these enzymes attractive targets for
structure-based drug design studies. However, very little has been done so far to
powerfully address the inhibitor design issues for this emerging type of BLs.
Here, we focus on the structural basis for molecular recognition and for broad
spectrum activity of class A carbapenemases: based on available 3-dimensional
structural information we identify a theoretical pharmacophoric model as a
starting point for the development of needed carbapenemases inhibitors.
PMID- 26424398
TI - B1-Metallo-beta-Lactamases: Where Do We Stand?
AB - Metallo-beta-Lactamases (MBLs) are class Bbeta-lactamases that hydrolyze almost
all clinically-availablebeta-lactam antibiotics. MBLs feature the distinctive
alphabeta/betaalpha sandwich fold of the metallo-hydrolase/oxidoreductase
superfamily and possess a shallow active-site groove containing one or two
divalent zinc ions, flanked by flexible loops. According to sequence identity and
zinc ion dependence, MBLs are classified into three subclasses (B1, B2 and B3),
of which the B1 subclass enzymes have emerged as the most clinically significant.
Differences among the active site architectures, the nature of zinc ligands, and
the catalytic mechanisms have limited the development of a common inhibitor. In
this review, we will describe the molecular epidemiology and structural studies
of the most prominent representatives of class B1 MBLs (NDM-1, IMP-1 and VIM-2)
and describe the implications for inhibitor design to counter this growing
clinical threat.
PMID- 26424402
TI - Targeting Receptor Tyrosine Kinases Using Monoclonal Antibodies: The Most
Specific Tools for Targeted-Based Cancer Therapy.
AB - Receptor tyrosine kinases (RTKs) family is comprised of different cell surface
glycoproteins. These enzymes participate in and regulate vital processes such as
cell proliferation, polarity, differentiation, cell to cell interactions,
signaling, and cell survival. Dysregulation of RTKs contributes to the
development of different types of tumors. RTKs deregulation in different types of
cancer has been reported for more than 30 RTKs. Due to their critical roles, the
specific targeting of RTKs in malignancies is a promising approach. Targeted
cellular and molecular therapies (personalized medicine) have been known as new
types of therapeutics, which prevent tumor cell proliferation and invasion by
interfering with molecules essential for tumor growth and survival. Specific
targeting of RTKs using monoclonal antibodies (mAbs) in malignancies as well as
in autoimmune disorders is of great interest. The growing number of mAbs approved
by the authorities implies on the increasing attentions and applications of these
therapeutic tools. Due to the high specificity, mAbs are the most promising
substances that target RTKs expressed on the tumor cell surface. In this
communication, we review the recent progresses in the development of mAbs
targeting oncogenic RTKs for cancer treatment.
PMID- 26424403
TI - Efflux Pump Inhibitors: A Novel Approach to Combat Efflux-Mediated Drug
Resistance in Bacteria.
AB - The increasing multi-drug resistance has become a major threat to the public
health. Overexpression of multidrug efflux pumps is one of the major mechanisms
of drug resistance in bacteria. Since active efflux of antibacterial agents plays
a significant role in mediating drug resistance in bacteria, the inhibition of
efflux pumps appears to be a promising strategy to restore antibacterial potency.
In recent years, in order to address this grave problem of multiple drug
resistance mediated by efflux pump, a large number of efflux pump inhibitors have
been discovered and tested, including natural products, antibiotics and synthetic
molecules. This review mainly describes recent achievements in the search for new
molecules that are able to inhibit efflux pumps in both Gram-positive and Gram
negative bacteria, in particular emphasis on natural and synthetic inhibitors of
the NorA efflux pump in Staphylococcus aureus, MexAB-OprM efflux pump in
Pseudomonas aeruginosa, and AcrAB-TolC efflux pump in Enterobacteriaceae, giving
special attention to their mechanisms of action, structure-activity relationships
and synergetic effect with clinically available antibiotics.
PMID- 26424405
TI - In Vivo Wear Performance of Cobalt-Chromium Versus Oxidized Zirconium Femoral
Total Knee Replacements.
AB - This study examines the damage and wear on the polyethylene (PE) inserts from 52
retrieved Genesis II total knee replacements to identify differences in
tribological performance between matched pairs of cobalt-chromium (CoCr) and
oxidized zirconium (OxZr) femoral components. Observer damage scoring and
microcomputed tomography were used to quantify PE damage and wear, respectively.
No significant differences were found between CoCr and OxZr groups in terms of PE
insert damage, surface penetration, or wear. No severe damage such as cracking or
delamination was noted on any of the 52 PE inserts. Observer damage scoring did
not correlate with penetrative or volumetric PE wear. The more costly OxZr
femoral component does not demonstrate clear tribological benefit over the
standard CoCr component in the short term with this total knee replacement
design.
PMID- 26424404
TI - Genotypic distribution and hepatic fibrosis among HIV/HCV co-infected individuals
in Southern China: a retrospective cross-sectional study.
AB - BACKGROUND: End-stage liver disease and hepatocellular carcinoma due to hepatitis
C virus (HCV) co-infection are increasingly common causes of death among HIV
infected individuals. However, there are few clinical investigations of HIV/HCV
co-infected individuals from low and middle-income nations. Here, we compare the
epidemiology of HCV-infected and HIV/HCV co-infected individuals in Southern
China and examine hepatic fibrosis scores in co-infected individuals. METHODS: We
conducted a retrospective cross-sectional study of treatment-naive HIV/HCV co
infected and HCV mono-infected subjects. Bivariate and multivariate models were
used to examine the association between demographics and HCV genotype. Among co
infected individuals, we also studied the relationship between fibrosis scores
derived from non-invasive studies and HCV genotype. RESULTS: Data were collected
from 175 HCV-infected individuals, including 89 (51 %) HIV/HCV co-infected
individuals. HIV/HCV co-infection was correlated with intravenous drug use (AOR
46.25, p < 0.001) and not completing high school (AOR 17.39, p < 0.001) in a
multivariate model. HIV/HCV co-infected individuals were more likely to be
infected with HCV genotype 6a (p < 0.0001) or 3a (p < 0.023), whereas increased
fibrosis (FIB-4 score) was associated with HCV genotype 3a infection (beta 2.18,
p < 0.001). DISCUSSION: Our results suggest that intravenous drug use is driving
HIV/HCV co-infection in Southern China. While additional studies are needed, HCV
genotype 6a is more common and genotype 3a appears to be associated with more
severe hepatic fibrosis in co-infected individuals. CONCLUSIONS: Future HIV/HCV
co-infection research in China should focus on at risk populations, HCV testing
uptake, and genotype-specific treatment.
PMID- 26424406
TI - Total Synthesis of (-)-Isoschizogamine.
AB - The total synthesis of (-)-isoschizogamine was accomplished, featuring the
construction of the quaternary carbon center by the modified Johnson-Claisen
rearrangement in basic media and the facile assembly of the key tetracyclic
quinolone intermediate through a cascade cyclization. The characteristic cyclic
aminal was constructed by late-stage C-H functionalization at the position
adjacent to the lactam nitrogen using a combination of CrO3 and nBu4 NIO4 and
subsequent Bi(OTf)3 -mediated cyclization.
PMID- 26424407
TI - Clonal dynamics in a single AML case tracked for 9 years reveals the complexity
of leukemia progression.
AB - Most types of cancers are made up of heterogeneous mixtures of genetically
distinct subclones. In particular, acute myeloid leukemia (AML) has been shown to
undergo substantial clonal evolution over the course of the disease. AML tends to
harbor fewer mutations than solid tumors, making it challenging to infer clonal
structure. Here, we present a 9-year, whole-exome sequencing study of a single
case at 12 time points, from the initial diagnosis until a fourth relapse,
including 6 remission samples in between. To the best of our knowledge, it covers
the longest time span of any data set of its kind. We used these time series data
to track the hierarchy and order of variant acquisition, and subsequently
analyzed the evolution of somatic variants to infer clonal structure. From this,
we postulate the development and extinction of subclones, as well as their
anticorrelated expansion via varying drug responses. In particular, we show that
new subclones started appearing after the first complete remission. The presence
and absence of different subclones during remission and relapses implies
differing drug responses among subclones. Our study shows that time series
analysis contrasting remission and relapse periods provides a much more
comprehensive view of clonal structure and evolution.
PMID- 26424408
TI - Determinants of hospital length of stay for people with serious mental illness in
England and implications for payment systems: a regression analysis.
AB - BACKGROUND: Serious mental illness (SMI), which encompasses a set of chronic
conditions such as schizophrenia, bipolar disorder and other psychoses, accounts
for 3.4 m (7 %) total bed days in the English NHS. The introduction of
prospective payment to reimburse hospitals makes an understanding of the key
drivers of length of stay (LOS) imperative. Existing evidence, based on mainly
small scale and cross-sectional studies, is mixed. Our study is the first to use
large-scale national routine data to track English hospitals' LOS for patients
with a main diagnosis of SMI over time to examine the patient and local area
factors influencing LOS and quantify the provider level effects to draw out the
implications for payment systems. METHODS: We analysed variation in LOS for all
SMI admissions to English hospitals from 2006 to 2010 using Hospital Episodes
Statistics (HES). We considered patients with a LOS of up to 180 days and
estimated Poisson regression models with hospital fixed effects, separately for
admissions with one of three main diagnoses: schizophrenia; psychotic and
schizoaffective disorder; and bipolar affective disorder. We analysed the
independent contribution of potential determinants of LOS including clinical and
socioeconomic characteristics of the patient, access to and quality of primary
care, and local area characteristics. We examined the degree of unexplained
variation in provider LOS. RESULTS: Most risk factors did not have a differential
effect on LOS for different diagnostic sub-groups, however we did find some
heterogeneity in the effects. Shorter LOS in the pooled model was associated with
co-morbid substance or alcohol misuse (4 days), and personality disorder (8
days). Longer LOS was associated with older age (up to 19 days), black ethnicity
(4 days), and formal detention (16 days). Gender was not a significant predictor.
Patients who self-discharged had shorter LOS (20 days). No association was found
between higher primary care quality and LOS. We found large differences between
providers in unexplained variation in LOS. CONCLUSIONS: By identifying key
determinants of LOS our results contribute to a better understanding of the
implications of case-mix to ensure prospective payment systems reflect accurately
the resource use within sub-groups of patients with SMI.
PMID- 26424409
TI - Variation in the ribosome interacting loop of the Sec61alpha from Giardia
lamblia.
AB - The interaction between the ribosome and the endoplasmic reticulum-located Sec61
protein translocon is mediated through an arginine residue of Sec61alpha, which
is conserved in all prokaryotic and eukaryotic orthologues characterized to date.
Using in silico approaches we report that instead of arginine, this ribosome
interaction function is most likely discharged by a lysine residue in the protist
Giardia lamblia. This functional substitution of the R with a K in GlSec61alpha
may have taken place to accommodate a G-rich rRNA.
PMID- 26424410
TI - Active ghrelin and the postpartum.
AB - Postpartum depression (PPD) occurs in 10-15 % of women. The appetite hormone
ghrelin, which fluctuates during pregnancy, is associated with depression in
nonpregnant samples. Here, we examine the association between PPD and active
ghrelin from pregnancy to postpartum. We additionally examine whether ghrelin
changes from pregnancy to postpartum and differs between breastfeeding and non
breastfeeding women. Sixty women who participated in a survey examining PPD and
had information in regard to ghrelin concentrations were included in the study.
The Edinburgh Postnatal Depression Scale was used to assess symptoms of PPD. Raw
ghrelin levels and ghrelin levels adjusted for creatinine were included as
outcomes. Women screening positive for PPD at 12 weeks postpartum had higher
pregnancy ghrelin concentrations. Ghrelin concentrations significantly decreased
from pregnancy to 6 weeks postpartum and this change differed based on pregnancy
depression status. Finally, ghrelin levels were lower in women who breastfed
compared with women who were bottle-feeding. No significant findings remained
once ghrelin levels were adjusted for creatinine. Although results do not suggest
an association between PPD and ghrelin after adjusting for creatinine, future
research should continue to explore this possibility extending further across the
postpartum period with larger sample sizes.
PMID- 26424411
TI - Prediction of biochemical recurrence after radical prostatectomy. New tool for
selecting candidates for adjuvant radiation therapy.
AB - OBJECTIVE: To design a risk summation to select patients for adjuvant radiation
therapy after prostatectomy. MATERIALS AND METHOD: A retrospective study was
conducted on 629 patients with localised prostate cancer (pN0-pNx) who were
treated with prostatectomy and with a prostate-specific antigen (PSA) value
<0.2ng/mL at 2-3 months. Biochemical recurrence was defined as a PSA >0.4ng/mL. A
multivariate Cox regression analysis was performed. A score (0-2) was assigned
according to the hazard ratio of the significant variables. The score summation
defined the risk summation. RESULTS: A total of 19.7% of the patients were pT3,
24.2% had a Gleason score >= 8, and 26.3% had positive surgical margins. The
median follow-up was 82 months. Some 26.6% of the patients experienced
biochemical recurrence. The identified prognostic variables independent of
biochemical recurrence were a Gleason score =7 (4+3) (HR, 2.01; P=.008), a
Gleason score >= 8 (HR, 3.07; P <.001), a pT3b stage (HR, 1.93; p=.008) and a
positive surgical margin (HR, 2.20; P<.001). We assigned 0 points to patients
without risk prognosis variables; 1 point to patients with Gleason scores =7
(4+3), pT3b or positive surgical margins; and 2 points to patients with Gleason
scores >= 8. The patients with a risk summation <= 2 had >50% survival free of
biochemical recurrence at 5 and 8 years. In contrast, the patients with a risk
summation >= 3 had <44% survival free of biochemical recurrence. CONCLUSION: The
patients with a risk summation <= 2 did not benefit from adjuvant radiation
therapy, while the patients with a risk summation >= 3 might benefit from
adjuvant radiation therapy.
PMID- 26424413
TI - p53 Mutants Access Epigenetic Pathways to Promote Tumor Growth.
AB - Mutations in p53 cause cancer cell growth by upregulating chromatin-modifying
enzymes.
PMID- 26424414
TI - High-Affinity PD-1 Protein Has Potential.
AB - A small, engineered protein that selectively binds to PD-L1 with very high
affinity was more effective in shrinking tumors in preclinical studies than
existing antibody-based immune checkpoint inhibitors, and it may overcome some
the drawbacks of these agents, according to data presented at the CRI-CIMT-EATI
AACR International Cancer Immunotherapy Conference.
PMID- 26424412
TI - Conceptualizing the neurobiology of non-suicidal self-injury from the perspective
of the Research Domain Criteria Project.
AB - Non-suicidal self-injury (NSSI) commonly starts in adolescence and is associated
with an array of negative outcomes. Neurobiological research investigating NSSI
is in its early stages and most studies have examined this behavior within the
context of specific diagnoses. However, the Research Domain Criteria (RDoC)
initiative encourages researchers to examine brain-behavior relationships across
diagnoses. This review on the neurobiology associated with NSSI is organized
using the domains proposed by RDoC: Negative Valence, Positive Valence,
Cognitive, Social Processes, and Arousal/Regulatory Systems. Evidence of
neurobiological anomalies is found in each of these domains. We also propose
future research directions, especially in regard to human development. Future
NSSI studies should address this behavior independent of diagnosis, examine
relevant constructs across multiple units of analysis, and assess how systems
change across development and course of illness. These advances will be essential
for guiding neurobiologically informed intervention and prevention strategies to
target NSSI. In doing so, we may prevent the associated negative outcomes across
the lifespan.
PMID- 26424415
TI - Avoiding the Personhood Issue: Abortion, Identity, and Marquis's 'Future-Like
Ours' Argument.
AB - One reason for the persistent appeal of Don Marquis' 'future like ours' argument
(FLO) is that it seems to offer a way to approach the debate about the morality
of abortion while sidestepping the difficult task of establishing whether the
fetus is a person. This essay argues that in order to satisfactorily address both
of the chief objections to FLO - the 'identity objection' and the 'contraception
objection' - Marquis must take a controversial stand on what is most essential to
being the kind of entity that an adult human being is. Such a stand amounts to a
controversial account of personhood. To the extent that FLO's success depends on
accepting such a controversial metaphysical view, one apparent attraction of FLO
proves illusory.
PMID- 26424418
TI - Do common genotypes of FK506 binding protein 5 (FKBP5) moderate the effects of
childhood maltreatment on cognition in schizophrenia and healthy controls?
AB - Common variants of the FK506 binding protein 5 (FKBP5) gene are implicated in
psychotic and other disorders, via their role in regulating glucocorticoid
receptor (GR) receptor sensitivity and effects on the broader function of the HPA
system in response to stress. In this study, the effects of four FKBP5
polymorphisms (rs1360780, rs9470080, rs4713902, rs9394309) on IQ and eight other
cognitive domains were examined in the context of exposure to childhood
maltreatment in 444 cases with schizophrenia and 292 healthy controls (from a
total sample of 617 cases and 659 controls obtained from the Australian
Schizophrenia Research Bank; ASRB). Participants subjected to any kind of
maltreatment (including physical, emotional, or sexual abuse or physical or
emotional neglect) in childhood were classified as 'exposed'; cognitive
functioning was measured with Repeatable Battery for the Assessment of
Neuropsychological Status, the Controlled Oral Word Association Test, and IQ was
estimated with the Weschler Test of Adult Reading. Hierarchical regressions were
used to test the main effects of genotype and childhood maltreatment, and their
additive interactive effects, on cognitive function. For rs1360870, there were
significant main effects of genotype and childhood maltreatment, and a
significant interaction of genotype with childhood trauma affecting attention in
both schizophrenia and healthy participants (C-homozygotes in both groups showed
worse attention in the context of maltreatment); in SZ, this SNP also affected
global neuropsychological function regardless of exposure to childhood trauma,
with T-homozygotes showing worse cognition than other genotypes. The mechanisms
of trauma-dependent effects of FKBP5 following early life trauma deserve further
exploration in healthy and psychotic samples, in the context of epigenetic
effects and perhaps epistasis with other genes. Study of these processes may be
particularly informative in subgroups exposed to various other forms of early
life adversity (i.e., birth complications, immigration).
PMID- 26424417
TI - Mood dysregulation and affective instability in emerging adults with childhood
maltreatment: An ecological momentary assessment study.
AB - Childhood maltreatment increases risk for mood, anxiety, substance use and
personality disorders and is associated with alterations in structure, function
and connectivity of brain regions involved in emotional regulation. We sought to
assess whether maltreatment was specifically associated with disturbances in
positive or negative mood regulation. Ecological momentary ratings were collected
with a wristwatch-like device with joy-stick (Seiko ecolog) approximately six
times per day over a week in 60 unmedicated participants (22 control, 38
maltreated, 18-25 years old). Forty-five percent of maltreated subjects had a
history of major depression but all were currently euthymic. Principal component
analysis with varimax rotation was used to provide orthogonal measures of
positive and negative valence, which were analyzed for indices of variability,
circadian rhythmicity and persistence, using linear and non-linear hierarchical
modeling and Hurst analysis. Groups did not differ in mean levels of positive or
negative affect. Maltreated subjects had increased variability and circadian and
hemicircadian abnormalities in ratings of positive but not negative affect.
Conversely, they had higher estimated Hurst exponents for negative but not
positive affect ratings indicating a greater degree of persistence. Abnormalities
in variability, rhythmicity and persistence were present in both maltreated
subjects with and without histories of major depression. These findings suggest
that both positive and negative valence systems may be dysregulated in
individuals with childhood maltreatment. However the nature of the dysregulation
appears to differ fundamentally in these domains, as positive mood ratings were
more variable and negative ratings more persistent.
PMID- 26424416
TI - Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration
ratio is associated with bipolar disorder episodes, and omega-3 plasma
concentrations are altered by treatment.
AB - OBJECTIVES: Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs) are molecular
modulators of neurotransmission and inflammation. We hypothesized that plasma
concentrations of n-3 PUFAs would be lower and those of n-6 PUFAs higher in
subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would
correlate with symptom severity in subjects with BD, and that effective treatment
would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we
explored clinical correlations and group differences in plasma levels of
saturated and monounsaturated fatty acids. METHODS: This observational, parallel
group study compared biomarkers between HCs (n = 31) and symptomatic subjects
with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma
concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha
linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid
(EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two
monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in
esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for
the five PUFAs, ratios of n-3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio
of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD
and HC groups were made with Student t-tests, and between the BD group at
baseline and follow-up using paired t-tests. Comparison of categorical variables
was performed using chi-square tests. Pearson's r was used for bivariate
correlations with clinical variables, including depressive and manic symptoms,
current panic attacks, and psychosis. RESULTS: UE EPA was lower in subjects with
BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however,
it was not statistically significant after correction for multiple comparisons.
No statistically significant difference was seen in any plasma PUFA concentration
between the BD and HC groups after Bonferroni correction for 40 comparisons, at p
< 0.001. Neither depressive severity nor mania severity was correlated
significantly with any PUFA concentration. Exploratory comparison showed lower
UE:E EPA in the BD than the HC group (p < 0.0001). At follow-up in the BD group,
UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory
correlations of clinical variables revealed that mania severity and suicidality
were positively correlated with UE:E EPA ratio, and that several plasma levels
and ratios correlated with panic disorder and psychosis. Depressive severity was
not correlated with any ratio. No plasma fatty acid level or ratio correlated
with self-reported n-3 PUFA intake or use of medication by class. CONCLUSIONS: A
large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio
of EPA in the symptomatic BD state may be important factors in vulnerability to a
mood state. Altered n-3 PUFA ratios could indicate changes in PUFA metabolism
concurrent with symptom improvement. Our findings are consistent with preclinical
and postmortem data and suggest testing interventions that increase n-3 and
decrease n-6 dietary PUFA intake.
PMID- 26424419
TI - Dysregulation of the NF-kappaB pathway as a potential inducer of bipolar
disorder.
AB - A century of investigations enhanced our understanding of bipolar disorder
although it remains a complex multifactorial disorder with a mostly unknown
pathophysiology and etiology. The role of the immune system in this disorder is
one of the most controversial topics in genetic psychiatry. Though inflammation
has been consistently reported in bipolar patients, it remains unclear how the
immunologic process influences the disorder. One of the core components of the
immune system is the NF-kappaB pathway, which plays an essential role in the
development of innate and adaptive immunity. Remarkably, the NF-kappaB pathway
received only little attention in bipolar studies, as opposed to studies of
related psychiatric disorders where immune dysregulation has been proposed to
explain the neurodegeneration in patient conditions. If immune dysregulation can
also explains the neurodegeneration in bipolar disorder, it will underscore the
role of the immune system in the chronicity and pathophysiology of the disorder
and may promote personalized therapeutic strategies. This is the first review to
summarize the current knowledge of the pathophysiological functions of NF-kappaB
in bipolar disorder.
PMID- 26424420
TI - The exclusion of people with psychiatric disorders from medical research.
AB - People with psychiatric disorders are excluded from medical research to an
unknown degree with unknown effects. We examined the prevalence of reported
psychiatric exclusion criteria using a sample of 400 highly-cited randomized
trials (2002-2010) across 20 common chronic disorders (6 psychiatric and 14 other
medical disorders). Two coders rated the presence of psychiatric exclusion
criteria for each trial. Half of all trials (and 84% of psychiatric disorder
treatment trials) reported possible or definite psychiatric exclusion criteria,
with significant variation across disorders (p < .001). Non-psychiatric
conditions with high rates of reported psychiatric exclusion criteria included
low back pain (75%), osteoarthritis (57%), COPD (55%), and diabetes (55%). The
most commonly reported type of psychiatric exclusion criteria were those related
to substance use disorders (reported in 48% of trials reporting at least one
psychiatric exclusion criteria). General psychiatric exclusions (e.g., "any
serious psychiatric disorder") were also prevalent (38% of trials). Psychiatric
disorder trials were more likely than other medical disorder trials to report
each specific type of psychiatric exclusion (p's < .001). Because published
clinical trial reports do not always fully describe exclusion criteria, this
study's estimates of the prevalence of psychiatric exclusion criteria are
conservative. Clinical trials greatly influence state-of-the-art medical care,
yet individuals with psychiatric disorders are often actively excluded from these
trials. This pattern of exclusion represents an under-recognized and worrisome
cause of health inequity. Further attention should be paid to how individuals
with psychiatric disorders can be safely included in medical research to address
this important clinical and social justice issue.
PMID- 26424421
TI - De novo cost-utility analysis of oral paliperidone in the treatment of
schizoaffective disorder.
AB - OBJECTIVES: The aim of this analysis is to compare costs and effectiveness of
paliperidone ER vs. placebo in the treatment of schizoaffective disorder (SAD) in
the Czech Republic based on pooled clinical trial data. METHODS: A de novo micro
simulation model was developed to assess the cost-utility analysis of
paliperidone vs. placebo as there is lack of clinical data comparing paliperidone
to other interventions. There are no studies primarily evaluating the efficacy of
treatment of SAD with other antipsychotics. The model estimated effectiveness and
costs of patients with SAD every week during 24-week time horizon. The
effectiveness was defined as improvement of a patient's PANSS score where
utilities were assigned to each modelled PANSS score. Based on the patient level
data a linear mixed-effects model was used to estimate the regression equations
of percentage decrease of PANSS score from the baseline. Utilities were computed
using a regression function of patients' age, sex and PANSS score, which was
adapted from a clinical study of patients with schizophrenia as there are no QoL
data on SAD patients. Among relevant costs, reflecting the payer's perspective,
costs of pharmacotherapy, concomitant medications and outpatient care were
considered. RESULTS: The average ICER of paliperidone compared to placebo reached
28,935 EUR/QALY. The probability of paliperidone being cost-effective compared to
placebo was 99.5%. CONCLUSIONS: Treatment of SAD with paliperidone results in
acceptable ICER and high probability of being cost-effective compared to placebo.
Thus, it can be considered as a cost-effective treatment of patients with SAD in
the Czech Republic.
PMID- 26424422
TI - The relationship between cortisol, stress and psychiatric illness: New insights
using hair analysis.
AB - BACKGROUND: Stress is an established important contributor to the development of
mental illness and stress related disorders. The biology implicated in the
homeostasis of pathological stress mechanisms is not fully established. One of
the difficulties with current techniques is the limitation in capturing chronic
levels of cortisol as an expression of stress levels in humans. Hair samples can
be used to evaluate cortisol levels averaged over relatively long periods of
time, therefore providing a more valid measure of chronic levels of this hormone.
A highly replicable technique to measure long-term cortisol could prove pivotal
in improving our understanding of the role of stress in psychiatric disorders.
METHODS: This review synthesises all the published studies relating hair cortisol
concentration (HCC) to stress and to psychiatric disorders. It describes and
summarises their findings with the aim of providing a summary picture of the
current state of this line of research. RESULTS: The strongest finding to date is
the replicable increases in hair cortisol associated with stressful life events.
Findings in psychiatric disorders are more sparse and inconsistent. There is some
support for the presence of raised HCC in major depressive disorders, and for
lowered HCC in posttraumatic stress disorder, suggesting chronic
hypercortisolaemia and hypocortisolaemia respectively. CONCLUSIONS: HCC is a
promising methodology to study chronic cortisol levels with the potential to help
characterise psychiatric and stress related disorders. The combination of chronic
and acute cortisol measurements has the potential for more accurately determining
different aspects of the stress response, and ultimately for the development of a
biological marker to aid diagnosis and response to treatment.
PMID- 26424423
TI - Effect of tyrosine supplementation on clinical and healthy populations under
stress or cognitive demands--A review.
AB - Consuming the amino-acid tyrosine (TYR), the precursor of dopamine (DA) and
norepinephrine (NE), may counteract decrements in neurotransmitter function and
cognitive performance. However, reports on the effectiveness of TYR
supplementation vary considerably, with some studies finding beneficial effects,
whereas others do not. Here we review the available cognitive/behavioral studies
on TYR, to elucidate whether and when TYR supplementation can be beneficial for
performance. The potential of using TYR supplementation to treat clinical
disorders seems limited and its benefits are likely determined by the presence
and extent of impaired neurotransmitter function and synthesis. Likewise, the
potential of TYR supplementation for enhancing physical exercise seems minimal as
well, perhaps because the link between physical exercise and catecholamine
function is mediated by many other factors. In contrast, TYR does seem to
effectively enhance cognitive performance, particularly in short-term stressful
and/or cognitively demanding situations. We conclude that TYR is an effective
enhancer of cognition, but only when neurotransmitter function is intact and DA
and/or NE is temporarily depleted.
PMID- 26424425
TI - Prevalence of postpartum depression among immigrant women: A systematic review
and meta-analysis.
AB - The aims of this systematic review and meta-analysis were threefold: to estimate
the prevalence of postpartum depressive symptoms in immigrant women, compare this
prevalence to non-immigrant women, and determine risk factors for postpartum
depressive symptoms in immigrant women. Literature searches were conducted in
PubMed, Embase, PsycINFO, Web of Science, Scopus, ResearchGate and Google Scholar
databases from 1950 until October 2014. Twenty-four studies met the inclusion
criteria of which 22 (12 cross-sectional and 10 prospective cohort) contributed
data for meta-analyses. Heterogeneity and publication bias were assessed. The
prevalence of postpartum depressive symptoms in immigrant women was 20% (95%
confidence interval [CI] 17-23%, 18 studies, N = 13,749 women). Immigrant women
were twice more likely to experience depressive symptoms in the postpartum period
than non-immigrant women (pooled unadjusted odds ratio [OR] = 2.10 [95% CI 1.62
2.73, 15 studies, N = 50,519 women] and adjusted OR = 2.18 [95% CI 1.60-2.96, 7
studies, N = 35,557 women]). There was, however, evidence of publication bias
with the pooled adjusted OR reduced to 1.63 (95% CI 1.22-2.17) after adjustment
for bias. Risk factors associated with postpartum depressive symptoms among
immigrant women included shorter length of residence in the destination country,
lower levels of social support, poorer marital adjustment, and perceived
insufficient household income. This study suggests that postpartum depression is
a common condition among immigrant women. Moreover, immigrant women are at higher
risk of postpartum depression than non-immigrant women. Further prospective
studies on the risk factors of postpartum depression among immigrant women
verified by a clinical diagnosis are needed.
PMID- 26424424
TI - Burning odor-elicited anxiety in OEF/OIF combat veterans: Inverse relationship to
gray matter volume in olfactory cortex.
AB - Despite the anatomical overlap between the brain's fear/threat and olfactory
systems, a very limited number of investigations have considered the role of
odors and the central olfactory system in the pathophysiology of PTSD. The goal
of the present study was to assess structural differences in primary and
secondary olfactory cortex between combat veterans with and without PTSD (CV +
PTSD, CV-PTSD, respectively). An additional goal was to determine the
relationship between gray matter volume (GMV) in olfactory cortex and the
distressing properties of burning-related odors. A region of interest voxel-based
morphometric (VBM) approach was used to measure GMV in olfactory cortex in a well
characterized group of CV + PTSD (n = 20) and CV-PTSD (n = 25). Prior to the MRI
exam, combat-related (i.e., burning rubber) and control odors were systematically
sampled and rated according to their potential for eliciting PTSD symptoms.
Results showed that CV + PTSD exhibited significantly reduced GMV in anterior
piriform (primary olfactory) and orbitofrontal (secondary olfactory) cortices
compared to CV-PTSD (both p < .01). For the entire group, GMV in bilateral
anterior piriform cortex was inversely related to burning rubber odor-elicited
memories of trauma (p < .05). GMV in orbitofrontal cortex was inversely related
to both clinical and laboratory measures of PTSD symptoms (all p < .05). In
addition to replicating an established inverse relationship between GMV in
anxiety-associated brain structures and PTSD symptomatology, the present study
extends those findings by being the first report of volumetric decreases in
olfactory cortex that are inversely related to odor-elicited PTSD symptoms.
Potential mechanisms underlying these findings are discussed.
PMID- 26424426
TI - Interacting effects of maternal responsiveness, infant regulatory problems and
dopamine D4 receptor gene in the development of dysregulation during childhood: A
longitudinal analysis.
AB - Recent longitudinal studies have indicated that affective and behavioral
dysregulation in childhood is associated with an increased risk for various
negative outcomes in later life. However, few studies to date have examined early
mechanisms preceding dysregulation during early childhood. Aim of this study was
to elucidate early mechanisms relating to dysregulation in later life using data
from an epidemiological cohort study on the long-term outcome of early risk
factors from birth to adulthood. At age 3 months, mothers and infants were
videotaped during a nursing and playing situation. Maternal responsiveness was
evaluated by trained raters. Infant regulatory problems were assessed on the
basis of a parent interview and direct observation by trained raters. At age 8
and 11 years, 290 children (139 males) were rated on the Child Behavior Checklist
(CBCL). Additionally, participants were genotyped for the dopamine D4 receptor
(DRD4) exon 3 VNTR polymorphism. A significant three-way interaction between
maternal responsiveness, DRD4 genotype and infant regulatory problems was
detected predicting the CBCL-dysregulation profile (CBCL-DP). Carriers of the
DRD4 7r allele with regulatory problems at age 3 months showed significantly more
behavior problems associated with the CBCL-DP during childhood when exposed to
less maternal responsiveness. In contrast, no effect of maternal responsiveness
was observed in DRD4 7r carriers without infant regulatory problems and in non
carriers of the DRD4 7r allele. This prospective longitudinal study extends
earlier findings regarding the association of the CBCL-DP with early parenting
and later psychopathology, introducing both DRD4 genotype and infant regulatory
problems as important moderators.
PMID- 26424428
TI - Efficacy and safety of a form of cranial electrical stimulation (CES) as an add
on intervention for treatment-resistant major depressive disorder: A three week
double blind pilot study.
AB - We examined efficacy and safety of one specific cranial electrical stimulator
(CES) device at a fixed setting in subjects with treatment-resistant major
depressive disorder (MDD). Thirty subjects (57% female, mean age 48.1 +/- 12.3
years) with MDD and inadequate response to standard antidepressants were
randomized to 3 weeks of treatment with CES (15/500/15,000 Hz, symmetrical
rectangular biphasic current of 1-4 mAmp, 40 V) or sham CES (device off) for 20
min, 5 days per week. The primary outcome measure was improvement in the 17-item
Hamilton Depression Rating Scale (HAM-D-17). Adverse effects (AEs) were assessed
using the Patient Related Inventory of Side Effects (PRISE). Completion rates
were 88% for CES, 100% for sham. Both treatment groups demonstrated improvement
of about 3-5 points in HAM-D-17 scores (p < 0.05 for both), and no significant
differences were observed between groups. Remission rates were 12% for CES, and
15% for sham, a nonsignificant difference. CES was deemed safe, with good
tolerability; poor concentration and malaise were the only distressing AEs that
differed significantly between CES and sham (p = 0.019 and p = 0.043,
respectively). Limitations include a small sample and lack of an active
comparator therapy. Although both treatment groups improved significantly, this
CES at the setting chosen did not separate from sham in this sample. Thus we
cannot rule out that the benefit from this setting used in this particular form
of CES was due to placebo effects. Since this form of CES has other settings,
future studies should test these settings and compare it against other CES
devices. Clinicaltrials.gov ID: NCT01325532.
PMID- 26424427
TI - The pro-inflammatory profile of depressed patients is (partly) related to
obesity.
AB - Many people with major depressive disorder (MDD) show evidence of systemic
inflammation, including elevations in inflammatory factors, but the cause is
unclear. The purpose of this analysis was to determine if obesity might
contribute to the pro-inflammatory state in MDD patients. Blood was obtained from
135 MDD patients and 50 controls. Serum was extracted and assayed for interleukin
(IL) -1beta, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, interferon-gamma
(IFNgamma), tumor necrosis factor alpha (TNFalpha), C-reactive protein (CRP),
leptin, and adiponectin using single- or multi-plex human immunoassay kits. The
primary analysis contrasted IL-6, TNFalpha, and CRP between MDD and control
groups with body mass index (BMI) as a covariate. The other analytes were
compared in an exploratory fashion. IL-6 (but not TNFalpha or CRP) showed
significant differences between MDD and controls even after covarying for BMI.
Obese controls and obese MDD groups were significantly higher in IL-6 than both
lean groups, but the two obese groups did not differ from each other. In the
exploratory analyses, the IL-2 level showed robust and significant differences
between MDD and controls even after covarying for BMI. Both lean and obese MDD
were higher than lean and obese controls. Adiponectin levels were also lower in
the MDD sample than controls. Prior findings of higher IL-6, and CRP in MDD
patients may be explained, at least in part, based on obesity. High IL-2,
however, was associated with depression and not obesity. The results have
significant implications for the understanding of pathophysiology and,
potentially treatment of MDD.
PMID- 26424429
TI - Comparing cognitive functions in medication adherent and non-adherent patients
with schizophrenia.
AB - BACKGROUND: Medication non-adherence presents a considerable problem in patients
with schizophrenia. Cognitive and executive functions can affect adherence. The
association between medication non-adherence and cognitive impairment in
schizophrenia is under investigated with limited and conflicting research data.
PURPOSE OF THE STUDY: To prospectively assess the rate of drug adherence among a
sample of patients with schizophrenia and to compare the cognitive and executive
functions between adherent and non-adherent patients. SUBJECTS AND METHODS: 109
patients with schizophrenia diagnosed according to the DSM-IV classification were
initially assessed by the Wechsler Adult Intelligence Scale (WAIS), Wechsler
Memory Scale-Revised (WMS-R) and Wisconsin Card Sorting Test (WCST) and six
months later by the Brief Adherence Rating Scale (BARS). RESULTS: 68.8% were non
adherent to their antipsychotic medication. Adherent patients (31.2%) had
significantly higher mean scores for the total, verbal and performance IQ. They
had significantly higher mean scores in most of WMS subtests (orientation,
information, verbal paired association, digit span, visual memory span), and
higher mean scores for; total correct, conceptual level response, percentage and
categories completed on the WSCT subscales (P < 0.0001). Whereas the non-adherent
group had higher mean scores in; trials administered, total errors, perseverative
responses, and perseverative errors (P < 0.0001). In a step regression analysis,
digit span, conceptualization, total and percentage of errors were putative
predictors of non-adherence. CONCLUSION: Cognitive deficits, especially verbal
memory and executive functions were the strongest patients' related factors
associated with non adherence to medication. Psychiatrists ought to consider
possible cognitive factors influencing adherence to enable offering proper
interventions.
PMID- 26424430
TI - The emerging field of retinal electrophysiological measurements in psychiatric
research: A review of the findings and the perspectives in major depressive
disorder.
AB - Major depressive disorder (MDD) is a severe mental illness leading to long-term
disabilities. One of the current challenges in psychiatric research is to develop
new approaches to investigate the pathophysiology of MDD and monitor drug
response in order to provide better therapeutic strategies to the patients. Since
the retina is considered as part of the central nervous system, it was suggested
that it constitutes an appropriate site to investigate mental illnesses. In the
past years, several teams assessed the retinal function of patients with mood
disorders and many relevant abnormalities have been reported. Investigation of
the retinal electrophysiological abnormalities in MDD remains a young emerging
field, but we believe that the current findings are very promising and we argue
that objective retinal electrophysiological measurements may eventually become
relevant tools to investigate the pathophysiology of MDD. Here, we review the
retinal abnormalities detected with objective electrophysiological measurements
such as the flash electroretinogram (fERG), the pattern electroretinogram (PERG)
and the electrooculogram (EOG) in patients with MDD. We discuss how these changes
might reflect the pathophysiology of MDD in both clinical and scientific points
of view, according especially to the monoamine neurotransmission deficiency
hypothesis. We also discuss the technical details that must be taken into
consideration for a potential use of the objective retinal electrophysiological
measurements as tools to investigate the pathophysiology of MDD.
PMID- 26424431
TI - Amygdala network dysfunction in late-life depression phenotypes: Relationships
with symptom dimensions.
AB - The amygdala, a crucial hub of the emotional processing neural system, has been
implicated in late-life depression (LLD) pathophysiology. However, the
overlapping and diverging amygdala network function abnormalities underlying two
clinical LLD phenotypes (i.e., LLD alone and LLD with mild cognitive impairment
[LLD-MCI]) are unknown. The aim of this study is to investigate the amygdala
functional connectivity (FC) differences between LLD alone, LLD-MCI and healthy
controls, and to examine the relationships between amygdala network dysfunction
and symptom dimensions. A resting-state functional connectivity magnetic
resonance imaging study was conducted to probe amygdala FC in a total of 63
elderly participants (LLD [n = 22], LLD-MCI [n = 15], and age- and gender-equated
healthy older adults [n = 26]) using a seed-based voxelwise R-fcMRI approach. LLD
only adults showed increased FC in the posterior default mode and vermis, and
diminished connections in the fronto-parietal, salience and temporal areas,
relative to controls. The LLD-MCI participants showed diminished FC in the
default mode, cognitive control, salience and visual regions, whereas increased
FC was limited to lateral parietal cortex compared with healthy controls. The LLD
MCI group also showed diminished FC in the occipital and posterior default mode
areas, relative to the LLD-only group. Distinct amygdala FC abnormalities that
explain depressive and anxiety symptom severity, and executive functioning were
identified. The amygdala FC impairments may distinguish LLD phenotypes. These
functional network abnormalities may also explain the heterogeneity seen in the
LLD clinical presentations.
PMID- 26424432
TI - Childhood trauma as a risk factor for psychosis: A sib-pair study.
AB - BACKGROUND: Childhood trauma, cannabis use and certain personality traits have
been related to the development of psychosis. This study uses a sib-pair design
to examine the association between childhood trauma and psychosis controlling for
cannabis use and neuroticism. METHODS: We evaluated 60 patient-sibling pairs,
conformed by patients with functional psychosis in the first five years of their
illness matched with a non-psychotic sibling. In univariate analyses, patients
and siblings were compared with McNemar tests and paired-sample t tests. A
conditional logistic regression model of the risk of developing psychosis was
built. The dependent variable of this model was the patient-sibling status
(patient = 1, sibling = 0). RESULTS: After controlling for cannabis use and
neuroticism, the odds of suffering psychosis for subjects who experienced a
childhood trauma were 7.3 times higher than the odds for subjects who did not
experience a childhood trauma [95% CI, (1.06-50.01); P = 0.04]. Also, after
controlling for experiencing childhood trauma and neuroticism, subjects who were
heavy cannabis users had odds of suffering psychosis that were 6.4 times higher
than the odds of the remaining subjects [95% CI, (1.2-35.2); P = 0.03].
CONCLUSION: Both childhood trauma and cannabis use were significantly associated
with an increased risk of suffering functional psychosis. A neurotic personality
also contributed independently to this risk. These findings might help improve
the prevention of psychosis and the development of specific treatment strategies
on this specific population.
PMID- 26424433
TI - Serum B cell-activating factor (BAFF) level in connective tissue disease
associated interstitial lung disease.
AB - BACKGROUND: Interstitial lung diseases (ILDs) are common in patients with
connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in
ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to
distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell
activating factor belonging to the tumour necrosis factor family (BAFF) plays a
crucial role in B cell development, survival, and antibody production. METHODS:
We examined serum levels of BAFF, surfactant protein D (SP-D), and Krebs von den
Lungen-6 (KL-6) in 33 patients with CTD-ILD, 16 patients with undifferentiated
CTD-ILD, 19 patients with CFIP, and 26 healthy volunteers. And we analysed the
relationship between serum BAFF levels and pulmonary function, as well as the
expression of BAFF in the lung tissue of patients with CTD-ILD. RESULTS: Serum
levels of BAFF were significantly higher in CTD-ILD patients compared to healthy
subjects and CFIP patients. However, there were no significant differences in
serum levels of SP-D and KL-6. Furthermore, serum BAFF levels in CTD-ILD patients
were inversely correlated with pulmonary function. BAFF was strongly expressed in
the lungs of CTD-ILD patients, but weakly in normal lungs. DISCUSSION: This is
the first study to demonstrate that serum BAFF levels were significantly higher
in CTD-ILD patients compared to healthy subjects and CFIP patients. Furthermore,
serum BAFF levels were correlated with pulmonary function. We consider that serum
BAFF levels in patients with CTD-ILD reflect the presence of ILDs disease
activity and severity. CONCLUSION: These finding suggest that BAFF may be a
useful marker for distinguishing CTD-ILD from CFIP.
PMID- 26424434
TI - Similarities and Contrasts in the Archaeal Community of Two Japanese Mountains:
Mt. Norikura Compared to Mt. Fuji.
AB - The community ecology, abundance, and diversity patterns of soil archaea are
poorly understood-despite the fact that they are a major branch of life that is
ubiquitous and important in nitrogen cycling in terrestrial ecosystems. We set
out to investigate the elevational patterns of archaeal ecology, and how these
compare with other groups of organisms. Many studies of different groups of
organisms (plants, birds, etc.) have shown a series of distinct communities with
elevation, and often a diversity maximum in mid-elevations. We investigated the
soil archaeal communities on Mt. Norikura, Japan, using 454 pyrosequencing of the
16S ribosomal RNA (rRNA) gene. There was a strong mid-elevation maximum in
diversity, and a mid-elevation maximum in abundance of soil archaea 16S rRNA and
amoA genes. These diversity and abundance maximums could not be correlated with
any identifiable soil parameter, nor plant diversity. Discrete, predictable
communities of archaea occurred at each elevational level, also not explicable in
terms of pH or major nutrients. When we compared the archaeal community and
diversity patterns with those found in an earlier study of Mt Fuji, both
mountains showed mid-elevation maximums in diversity and abundance of archaea,
possibly a result of some common environmental factor such as soil disturbance
frequency. However, they showed distinct sets of archaeal communities at similar
elevational sampling points. Presumably, the difference reflects their distinct
geology (Norikura being andesitic, while Fuji is basaltic) and the resulting
combinations of soil chemistry and environmental conditions, although no
explanatory variable was found. Clearly, many soil archaea have strongly defined
niches and will only occur in a narrow subset of the range of possible climate
and soil conditions. The findings of a mid-elevation diversity maximum on
Norikura provides a further instance of how widespread this unexplained pattern
is in nature, in a wide variety of groups of organisms.
PMID- 26424435
TI - Drug-induced systemic lupus erythematosus in a child after 3 years of treatment
with carbamazepine.
AB - Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic
lupus erythematosus (SLE) that generally resolves within weeks or months after
the withdrawal of the implicated drug. DILE is unusual during childhood, with the
most frequent age of presentation being at 50-70 years of age. Among different
drugs, most commonly procainamide and hydralazine have been implicated as a cause
of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few
cases have been reported in children. We describe the case of CBZ-induced SLE in
a 9-year-old girl following 3 years of CBZ therapy. This case report shows that
drug-induced SLE is an important side-effect to be considered, even after long
term treatment with CBZ, and also during childhood.
PMID- 26424437
TI - The Basic Empathy Scale adapted to French middle childhood: Structure and
development of empathy.
AB - We adapted the adult French version of the Basic Empathy Scale to French children
aged 6-11 years, in order to probe the factorial structure underlying empathy. A
total of 410 children (189 girls and 221 boys) were instructed to fill out the
resulting Basic Empathy Scale in Children (BES-C). Results showed that, as in
adulthood, the three-factor model of empathy (i.e., emotional contagion,
cognitive empathy, and emotional disconnection) was more relevant than the one-
and two-factor ones. This means that as early as 6 years of age, children's
responses should reflect the same organization of the three components of empathy
as those of adults. In line with the literature, cognitive empathy increased and
emotional disconnection decreased in middle childhood, while emotional contagion
remained stable. Moreover, girls exhibited greater emotional contagion than boys,
with the reverse pattern being observed for emotional disconnection. No sex
difference was found regarding cognitive empathy.
PMID- 26424439
TI - Erratum to: Efficient simulation of diffusion-based choice RT models on CPU and
GPU.
PMID- 26424438
TI - The Novel Object and Unusual Name (NOUN) Database: A collection of novel images
for use in experimental research.
AB - Many experimental research designs require images of novel objects. Here we
introduce the Novel Object and Unusual Name (NOUN) Database. This database
contains 64 primary novel object images and additional novel exemplars for ten
basic- and nine global-level object categories. The objects' novelty was
confirmed by both self-report and a lack of consensus on questions that required
participants to name and identify the objects. We also found that object novelty
correlated with qualifying naming responses pertaining to the objects' colors.
The results from a similarity sorting task (and a subsequent multidimensional
scaling analysis on the similarity ratings) demonstrated that the objects are
complex and distinct entities that vary along several featural dimensions beyond
simply shape and color. A final experiment confirmed that additional item
exemplars comprised both sub- and superordinate categories. These images may be
useful in a variety of settings, particularly for developmental psychology and
other research in the language, categorization, perception, visual memory, and
related domains.
PMID- 26424436
TI - Novel p75 neurotrophin receptor ligand stabilizes neuronal calcium, preserves
mitochondrial movement and protects against HIV associated neuropathogenesis.
AB - Human immunodeficiency virus (HIV) rapidly penetrates into the brain and
establishes a persistent infection of macrophages/microglia. Activation of these
cells by HIV results in the secretion of soluble factors that destabilize
neuronal calcium homeostasis, encourage oxidative stress and result in neural
damage. This damage is thought to underlie the cognitive-motor dysfunction that
develops in many HIV-infected patients. Studies have suggested that neurotrophins
may protect neurons from the toxic effects of HIV-associated proteins. To better
understand the pathogenic mechanisms and the neuroprotective potential of
neurotrophin ligands, we evaluated neuronal damage, calcium homeostasis and
mitochondrial functions after exposure of cultured rat neurons directly to HIV
gp120 or to conditioned medium from human monocyte-derived macrophages treated
with gp120. We then assessed the ability of a new non-peptide p75 neurotrophin
receptor ligand, LM11A-31, to stabilize calcium homeostasis and prevent the
development of pathology. Each toxic challenge resulted in a delayed accumulation
of intracellular calcium coupled to a decrease in the rate of calcium clearance
from the cell. The delayed calcium accumulation correlated with the development
of focal dendritic swellings (beading), cytoskeletal damage and impaired movement
of mitochondria. Addition of LM11A-31 to the cultures at nanomolar concentrations
eliminated cell death, significantly reduced the pathology, suppressed the
delayed accumulation of calcium and restored mitochondrial movements. The potent
neuroprotection and the stabilization of calcium homeostasis indicate that LM11A
31 may have excellent potential for the treatment of HIV-associated
neurodegeneration.
PMID- 26424440
TI - Evidence-based recommendations for designing free-sorting experiments.
AB - The card-sorting task is a flexible research tool that is widely used across many
of the subfields of psychology. Yet this same great flexibility requires
researchers to make several (seemingly arbitrary) decisions in their designs,
such as fixing a sufficient number of objects to sort, setting task requirements,
and creating task instructions for participants. In the present research, we
provide a systematic empirical investigation of the consequences of typical
researcher design choices while administering sorting tasks. Specifically, we
studied the effects of seven sorting task design factors by collecting data from
over 1,000 online participants assigned to one of 36 sorting tasks, as part of a
fractional factorial experimental design. Analyses show the effects of the
various researcher decisions on the probability that participants would quit the
task, the amount of time spent on the task, the number of piles made, and
posttask measures such as satisfaction and depletion. Research design
recommendations are provided.
PMID- 26424441
TI - Normative study of theme identifiability: Instructions with and without
explanation of the false memory effect.
AB - False-memory illusions have been widely studied using the Deese/Roediger
McDermott paradigm (DRM). In this paradigm, words semantically related to a
single nonpresented critical word are studied. In a later memory test, critical
words are often falsely recalled and recognized. The present normative study was
conducted to measure the theme identifiability of 60 associative word lists in
Spanish that include six words (e.g., stove, coat, blanket, scarf, chill, and
bonnet) that are simultaneously associated with three critical words (e.g., HEAT,
COLD, and WINTER; Beato & Diez, Psicothema, 26, 457-463, 2011). Different levels
of backward associative strength were used in the construction of the DRM lists.
In addition, we used two types of instructions to obtain theme identifiability.
In the without-explanation condition, traditional instructions were used,
requesting participants to write the theme list. In the with-explanation
condition, the false-memory effect and how the lists were built were explained,
and an example of a DRM list and critical words was shown. Participants then had
to discover the critical words. The results showed that all lists produced theme
identifiability. Moreover, some lists had a higher theme identifiability rate
(e.g., 61 % for the critical words LOVE, BOYFRIEND, COUPLE) than others (e.g., 24
% for CITY, PLACE, VILLAGE). After comparing the theme identifiabilities in the
different conditions, the results indicated higher theme identifiability when the
false-memory effect was explained than without such an explanation. Overall,
these new normative data provide a useful tool for those experiments that, for
example, aim to analyze the wide differences observed in false memory with DRM
lists and the role of theme identifiability.
PMID- 26424442
TI - CRIE: An automated analyzer for Chinese texts.
AB - Textual analysis has been applied to various fields, such as discourse analysis,
corpus studies, text leveling, and automated essay evaluation. Several tools have
been developed for analyzing texts written in alphabetic languages such as
English and Spanish. However, currently there is no tool available for analyzing
Chinese-language texts. This article introduces a tool for the automated analysis
of simplified and traditional Chinese texts, called the Chinese Readability Index
Explorer (CRIE). Composed of four subsystems and incorporating 82 multilevel
linguistic features, CRIE is able to conduct the major tasks of segmentation,
syntactic parsing, and feature extraction. Furthermore, the integration of
linguistic features with machine learning models enables CRIE to provide leveling
and diagnostic information for texts in language arts, texts for learning Chinese
as a foreign language, and texts with domain knowledge. The usage and validation
of the functions provided by CRIE are also introduced.
PMID- 26424443
TI - The EU-Emotion Stimulus Set: A validation study.
AB - The EU-Emotion Stimulus Set is a newly developed collection of dynamic multimodal
emotion and mental state representations. A total of 20 emotions and mental
states are represented through facial expressions, vocal expressions, body
gestures and contextual social scenes. This emotion set is portrayed by a multi
ethnic group of child and adult actors. Here we present the validation results,
as well as participant ratings of the emotional valence, arousal and intensity of
the visual stimuli from this emotion stimulus set. The EU-Emotion Stimulus Set is
available for use by the scientific community and the validation data are
provided as a supplement available for download.
PMID- 26424444
TI - Depressive symptom trajectories over a 6-year period following myocardial
infarction: predictive function of cognitive appraisal and coping.
AB - The association between distinct patterns of depression and coping variables in
myocardial infarction (MI) survivors over the long-term is unclear. The study
aims to evaluate depressive trajectories and their covariates, including coping
and cognitive appraisal, following MI over a period of 6 years. Depressive
symptoms were assessed in 200 patients a few days after the first MI, and 1
month, 6 months and 6 years later. Cognitive appraisal and coping were assessed
during the first three time points. Three latent depressive trajectories were
identified: chronic (high; increasing then decreasing; n = 49), rising (moderate;
decreasing then increasing; n = 121) and low (low; decreasing then stabilizing; n
= 30). The chronic trajectory was associated with higher negative appraisal and
emotion-focused coping. The findings clarify the long-term longitudinal
trajectories of post-MI depressive symptoms and their association with coping
variables, revealing the unfavorable impact of negative cognition and palliative
coping.
PMID- 26424445
TI - Cow hair allergen concentrations in dairy farms with automatic and conventional
milking systems: From stable to bedroom.
AB - Bovine hair and dander are considered to be a notable risk factor for
sensitization and allergic symptoms in occupationally exposed cattle farmers due
to various IgE binding proteins. Farmers are suspected not only to be exposed
during their work inside the stables but also inside their homes as allergens
could be transferred via hair and clothes resulting in continued bovine allergen
exposure in private areas. In recent years a new sensitive sandwich ELISA (enzyme
linked immunosorbent assay) test has been developed to measure the cow hair
allergen (CHA) concentration in dust. The aim of the present study was to
determine the CHA concentration in airborne and settled dust samples in stables
and private rooms of dairy cattle farms with automatic milking systems (AM) and
conventional milking systems (CM), also with respect to questionnaire data on
farming characteristics. For this purpose different sampling techniques were
applied, and results and practicability of the techniques were compared. Dust
sampling was performed in the stable, computer room (only AM), changing room,
living room and bedroom (mattress) of 12 dairy farms with automatic milking
systems (AM group) and eight dairy farms with conventional milking systems (CM
group). Altogether, 90 samples were taken by ALK filter dust collectors from all
locations, while 32 samples were collected by an ion charging device (ICD) and 24
samples by an electronic dust fall collector (EDC) in computer rooms (AM) and/or
changing and living rooms (not stables). The dust samples were extracted and
analyzed for CHA content with a sandwich ELISA. At all investigated locations,
CHA concentrations were above the limit of detection (LOD) of 0.1 ng/ml dust
extract. The median CHA concentrations in dust collected by ALK filters ranged
from 63 to 7154 MUg/g dust in AM farms and from 121 to 5627 MUg/g dust in CM
farms with a steep concentration gradient from stables to bedrooms. ICD sampling
revealed median CHA contents of 112 MUg/g airborne dust in the computer rooms of
the AM farms and median CHA loads of 5.6 MUg/g (AM farms) and 19.8 MUg/g (CM
farms) in the living rooms. Passive dust sampling by EDC was performed only at
two locations in the AM group resulting in median CHA values of 116 MUg/m(2)
(computer room) and 55.0 MUg/m(2) (changing room). Except for the stable samples
the median CHA load was lower in AM farms compared to CM farms. The CHA contents
of ALK filter samples were significantly correlated in most locations.
Differences between the farming types were not significant. Although allergen
transfer to the private area of the farmers has been found and results from
several locations were correlated, differences in CHA concentrations were not
significant with respect to questionnaire data such as the wearing of stable
clothes in living room, free access of pets to stable and home, frequency of hair
washing. All sampling techniques seem to being practicable for simple and
effective CHA measurement.
PMID- 26424447
TI - X-ray microtomography using correlation of near-field speckles for material
characterization.
AB - Nondestructive microscale investigation of objects is an invaluable tool in life
and materials sciences. Currently, such investigation is mainly performed with X
ray laboratory systems, which are based on absorption-contrast imaging and cannot
access the information carried by the phase of the X-ray waves. The phase signal
is, nevertheless, of great value in X-ray imaging as it is complementary to the
absorption information and in general more sensitive to visualize features with
small density differences. Synchrotron facilities, which deliver a beam of high
brilliance and high coherence, provide the ideal condition to develop such
advanced phase-sensitive methods, but their access is limited. Here we show how a
small modification of a laboratory setup yields simultaneously quantitative and
3D absorption and phase images of the object. This single-shot method is based on
correlation of X-ray near-field speckles and represents a significant broadening
of the capabilities of laboratory-based X-ray tomography.
PMID- 26424448
TI - STIM1-Ca2+ signaling modulates automaticity of the mouse sinoatrial node.
AB - Cardiac pacemaking is governed by specialized cardiomyocytes located in the
sinoatrial node (SAN). SAN cells (SANCs) integrate voltage-gated currents from
channels on the membrane surface (membrane clock) with rhythmic Ca(2+) release
from internal Ca(2+) stores (Ca(2+) clock) to adjust heart rate to meet
hemodynamic demand. Here, we report that stromal interaction molecule 1 (STIM1)
and Orai1 channels, key components of store-operated Ca(2+) entry, are
selectively expressed in SANCs. Cardiac-specific deletion of STIM1 in mice
resulted in depletion of sarcoplasmic reticulum (SR) Ca(2+) stores of SANCs and
led to SAN dysfunction, as was evident by a reduction in heart rate, sinus
arrest, and an exaggerated autonomic response to cholinergic signaling. Moreover,
STIM1 influenced SAN function by regulating ionic fluxes in SANCs, including
activation of a store-operated Ca(2+) current, a reduction in L-type Ca(2+)
current, and enhancing the activities of Na(+)/Ca(2+) exchanger. In conclusion,
these studies reveal that STIM1 is a multifunctional regulator of Ca(2+) dynamics
in SANCs that links SR Ca(2+) store content with electrical events occurring in
the plasma membrane, thereby contributing to automaticity of the SAN.
PMID- 26424449
TI - Fibonacci family of dynamical universality classes.
AB - Universality is a well-established central concept of equilibrium physics.
However, in systems far away from equilibrium, a deeper understanding of its
underlying principles is still lacking. Up to now, a few classes have been
identified. Besides the diffusive universality class with dynamical exponent
[Formula: see text], another prominent example is the superdiffusive Kardar
Parisi-Zhang (KPZ) class with [Formula: see text]. It appears, e.g., in low
dimensional dynamical phenomena far from thermal equilibrium that exhibit some
conservation law. Here we show that both classes are only part of an infinite
discrete family of nonequilibrium universality classes. Remarkably, their
dynamical exponents [Formula: see text] are given by ratios of neighboring
Fibonacci numbers, starting with either [Formula: see text] (if a KPZ mode exist)
or [Formula: see text] (if a diffusive mode is present). If neither a diffusive
nor a KPZ mode is present, all dynamical modes have the Golden Mean [Formula: see
text] as dynamical exponent. The universal scaling functions of these Fibonacci
modes are asymmetric Levy distributions that are completely fixed by the
macroscopic current density relation and compressibility matrix of the system and
hence accessible to experimental measurement.
PMID- 26424450
TI - ACHT4-driven oxidation of APS1 attenuates starch synthesis under low light
intensity in Arabidopsis plants.
AB - The regulatory mechanisms that use signals of low levels of reactive oxygen
species (ROS) could be obscured by ROS produced under stress and thus are better
investigated under homeostatic conditions. Previous studies showed that the
chloroplastic atypical thioredoxin ACHT1 is oxidized by 2-Cys peroxiredoxin (2
Cys Prx) in Arabidopsis plants illuminated with growth light and in turn
transmits a disulfide-based signal via yet unknown target proteins in a feedback
regulation of photosynthesis. Here, we studied the role of a second chloroplastic
paralog, ACHT4, in plants subjected to low light conditions. Likewise, ACHT4
reacted in planta with 2-Cys Prx, indicating that it is oxidized by a similar
disulfide exchange reaction. ACHT4 further reacted uniquely with the small
subunit (APS1) of ADP-glucose pyrophosphorylase (AGPase), the first committed
enzyme of the starch synthesis pathway, suggesting that it transfers the
disulfides it receives from 2-Cys Prx to APS1 and turns off AGPase. In
accordance, ACHT4 participated in an oxidative signal that quenched AGPase
activity during the diurnal transition from day to night, and also in an
attenuating oxidative signal of AGPase in a dynamic response to small
fluctuations in light intensity during the day. Increasing the level of expressed
ACHT4 or of ACHT4DeltaC, a C terminus-deleted form that does not react with APS1,
correspondingly decreased or increased the level of reduced APS1 and decreased or
increased transitory starch content. These findings imply that oxidative control
mechanisms act in concert with reductive signals to fine tune starch synthesis
during daily homeostatic conditions.
PMID- 26424452
TI - Extreme events in computational turbulence.
AB - We have performed direct numerical simulations of homogeneous and isotropic
turbulence in a periodic box with 8,192(3) grid points. These are the largest
simulations performed, to date, aimed at improving our understanding of
turbulence small-scale structure. We present some basic statistical results and
focus on "extreme" events (whose magnitudes are several tens of thousands the
mean value). The structure of these extreme events is quite different from that
of moderately large events (of the order of 10 times the mean value). In
particular, intense vorticity occurs primarily in the form of tubes for
moderately large events whereas it is much more "chunky" for extreme events
(though probably overlaid on the traditional vortex tubes). We track the temporal
evolution of extreme events and find that they are generally short-lived. Extreme
magnitudes of energy dissipation rate and enstrophy occur simultaneously in space
and remain nearly colocated during their evolution.
PMID- 26424451
TI - Drosophila E-cadherin is required for the maintenance of ring canals anchoring to
mechanically withstand tissue growth.
AB - Intercellular bridges called "ring canals" (RCs) resulting from incomplete
cytokinesis play an essential role in intercellular communication in somatic and
germinal tissues. During Drosophila oogenesis, RCs connect the maturing oocyte to
nurse cells supporting its growth. Despite numerous genetic screens aimed at
identifying genes involved in RC biogenesis and maturation, how RCs anchor to the
plasma membrane (PM) throughout development remains unexplained. In this study,
we report that the clathrin adaptor protein 1 (AP-1) complex, although
dispensable for the biogenesis of RCs, is required for the maintenance of the
anchorage of RCs to the PM to withstand the increased membrane tension associated
with the exponential tissue growth at the onset of vitellogenesis. Here we
unravel the mechanisms by which AP-1 enables the maintenance of RCs' anchoring to
the PM during size expansion. We show that AP-1 regulates the localization of the
intercellular adhesion molecule E-cadherin and that loss of AP-1 causes the
disappearance of the E-cadherin-containing adhesive clusters surrounding the RCs.
E-cadherin itself is shown to be required for the maintenance of the RCs'
anchorage, a function previously unrecognized because of functional compensation
by N-cadherin. Scanning block-face EM combined with transmission EM analyses
reveals the presence of interdigitated, actin- and Moesin-positive, microvilli
like structures wrapping the RCs. Thus, by modulating E-cadherin trafficking, we
show that the sustained E-cadherin-dependent adhesion organizes the microvilli
meshwork and ensures the proper attachment of RCs to the PM, thereby
counteracting the increasing membrane tension induced by exponential tissue
growth.
PMID- 26424454
TI - Testing spatial measures of alcohol outlet density with self-rated health in the
Australian context: Implications for policy and practice.
AB - INTRODUCTION AND AIMS: Reducing access to alcohol is an important and cost
effective strategy for decreasing alcohol consumption and associated harm. Yet
this is a less common approach to alcohol control in Australia. The aim of this
research was to ascertain which alcohol outlet density spatial measures were
related to long-term health outcomes, and the extent to which this differs for
those living in more or less disadvantaged neighbourhoods. DESIGN AND METHODS:
Existing Australian state-level spatial alcohol policies were reviewed. No
appropriate spatial policies were identified; therefore, the literature was used
to identify potential alcohol-related spatial measures. Spatial measures of
alcohol outlet density were generated in a geographical information system and
linked with health survey data drawn from 3141 adults living in metropolitan
Melbourne. Logistic regression analysis was used to examine associations between
alcohol outlet density measures, self-rated health and area-level disadvantage.
RESULTS: Twelve spatial measures of alcohol outlet density were generated.
Alcohol outlet density and self-rated health associations varied by area-level
disadvantage. For those living in more disadvantaged areas, not having off
licenses available within 800 m, or on-licenses available within 400 m were
protective of self-rated health. DISCUSSION AND CONCLUSIONS: Local alcohol outlet
density may have a more detrimental effect on self-rated health for those living
in more disadvantaged neighbourhoods, compared with those living in more
advantaged areas. There is a need for spatial alcohol policies to help reduce
alcohol-related harm. This research proposes a set of spatial measures to
generate a more consistent understanding of alcohol availability in Australia.
[Badland H, Mavoa S, Livingston M, David S, Giles-Corti B. Testing spatial
measures of alcohol outlet density with self-rated health in the Australian
context: Implications for policy and practice. Drug Alcohol Rev 2016;35:298-306].
PMID- 26424455
TI - The long shadows of past mistakes.
PMID- 26424453
TI - Splicing noncoding RNAs from the inside out.
AB - Eukaryotic precursor-messenger RNAs (pre-mRNAs) undergo splicing to remove
intragenic regions (introns) and ligate expressed regions (exons) together.
Unlike exons in the mature messenger RNAs (mRNAs) that are used for translation,
introns that are spliced out of pre-mRNAs were generally believed to lack
function and to be degraded. However, recent studies have revealed that a large
group of spliced introns can escape complete degradation and are processed to
generate noncoding RNAs (ncRNAs), including different types of small RNAs, long
noncoding RNAs, and circular RNAs. Strikingly, exonic sequences can be also back
spliced from pre-mRNAs to form stable circular RNAs. Together, the findings that
ncRNAs can be spliced out of mRNA precursors not only expand the ever-growing
repertoire of ncRNAs that originate from different genomic regions, but also
reveal the unexpected transcriptomic complexity and functional capacity of
eukaryotic genomes.
PMID- 26424456
TI - Second-line antiretroviral therapy and the human factor.
PMID- 26424457
TI - Should everyone ageing with HIV take a statin?
PMID- 26424458
TI - HIV in Thai men who have sex with men: a sustained emergency.
PMID- 26424459
TI - HIV surveys in older adults: better data, better health.
PMID- 26424462
TI - Temporal trends in HIV-1 incidence and risk behaviours in men who have sex with
men in Bangkok, Thailand, 2006-13: an observational study.
AB - BACKGROUND: HIV-1 incidence in men who have sex with men (MSM) is often difficult
to estimate. We therefore assessed temporal trends in HIV-1 incidence and
behavioural risk factors in MSM in Bangkok, Thailand, from 2006 to 2013. METHODS:
In this observational study, we used data for clients attending the Silom
Community Clinic for voluntary counselling and testing (VCT) services and from
the Bangkok MSM Cohort Study (BMCS) to investigate trends in HIV incidence per
100 person-years per quarter in both cohorts. During VCT, basic demographic data
were gathered at registration. However, no behavioural risk data were gathered.
In the BMCS, we gathered demographic and behavioural data at baseline and at
regular study visits using audio computer-assisted self-interviewing. Questions
were included about potential risk factors such as drug use, sexual practices,
and how often condoms were used. We also analysed behavioural risk factors in the
BMCS cohort, using a restricted cubic spline function for time. FINDINGS: From
2006 to 2013, 8176 MSM came for VCT; 1999 (24%) clients were initially
seronegative and returned for another test. 235 (12%) individuals seroconverted.
The overall HIV-1 incidence was 5.5 per 100 person-years (95% CI 4.8-6.3), with
an increasing trend (adjusted p=0.02). In the BMCS, 1372 people were seronegative
at baseline; 1259 (92%) had more than one follow-up test and 238 (17%)
seroconverted. The overall HIV-1 incidence was 5.3 per 100 person-years (95% CI
4.7-6.1), with an increase and then a decline (inverted U-shaped curve,
p=0.0001). Individuals aged 21 years and younger were at significantly higher
risk of HIV infection than were those aged 30 years and older in the in the VCT
(rate ratio 2.29, 95% CI 1.88-2.78, p<0.0001) and BMCS cohorts (1.99, 1.50-2.65,
p<0.0001). Overall, drug use (p=0.03), drug use to enhance sex (p=0.0006), use of
drugs for erectile dysfunction (p<0.0001), and 100% condom use (p<0.0001)
increased over time, whereas the proportion of individuals reporting receptive
anal intercourse decreased (p=0.004). INTERPRETATION: With a sustained high HIV-1
incidence and increasing drug use in MSM in Bangkok, we urgently need innovative
and acceptable HIV prevention interventions, especially for young MSM. FUNDING:
US Centers for Disease Control and Prevention.
PMID- 26424460
TI - Baseline HIV-1 resistance, virological outcomes, and emergent resistance in the
SECOND-LINE trial: an exploratory analysis.
AB - BACKGROUND: WHO-recommended second-line antiretroviral therapy (ART) of a
pharmacologically enhanced (boosted) protease inhibitor plus nucleoside or
nucleotide reverse transcriptase inhibitors (NtRTIs) might be compromised by
resistance. Results of the 96 week SECOND-LINE randomised trial showed that NtRTI
sparing ART with ritonavir-boosted lopinavir and raltegravir (raltegravir-group)
provided non-inferior efficacy to ritonavir-boosted lopinavir and two or three
NtRTIs (NtRTI-group) in participants with virological failure composed of a first
line regimen of a non-nucleoside reverse transcriptase inhibitor plus two NtRTIs.
We report the relation of baseline virological resistance with virological
failure and emergent resistance on study. METHODS: As part of the randomised open
label SECOND-LINE trial, second-line ART NtRTI selection was made by either
genotype (local laboratory) or algorithm. Genotypic resistance for the entire
cohort at baseline was assessed on stored samples at a central laboratory.
Virological failure was defined as plasma viral load greater than 200 copies per
mL. Baseline viral isolates were assigned genotypic sensitivity scores (GSSs) by
use of the Stanford HIV Database version 6.3.1: a global GSS (gGSS), defined as
the combined GSS for lamivudine or emtricitabine, abacavir, zidovudine,
stavudine, didanosine, and tenofovir and a specific GSS (sGSS) defined as the GSS
for the ART regimen initiated by a specific participant. Emergent resistance was
reported on samples with a viral load greater than 500 copies per mL. We used
multivariate logistic regression with backward elimination to assess predictors
of virological failure and emergent resistance. FINDINGS: From April 19, 2010, to
July 22, 2013, 271 patients were included in the NtRTI group and and 270 in the
raltegravir group. In the NtRTI group 215 had available baseline sequence data,
and 240 had viral load measurements at 96 weeks; in the raltegravir group 236 had
baseline sequence data and 255 had viral load measurements at 96 weeks. Median
(IQR) gGSS was 3.0 (1.3-4.3) in the NtRTI group and 3.0 (1.0-4.3) in the
raltegravir group. The median sGSS in the NtRTI group was 1.0 (0.5-1.8).
Multivariate analysis showed significant associations between virological failure
and less than complete adherence at week 4 (odds ratio [OR] 2.18, 95%CI 1.07
4.47; p=0.03) and week 48 (2.49, 1.09-5.69; p=0.03), baseline plasma viral load
greater than 100,000 copies per mL (3.43, 1.70-6.94; p=0.0006), baseline gGSS
>4.25 (4.73, 1.94-11.6; p=0.0007), and being Hispanic (3.13, 1.21-8.13; p=0.02)
or African (3.49, 1.68-7.28; p=0.0008) rather than Asian. We observed emergent
major mutations in one (1%) of 129 participants for protease (both groups), eight
(13%) of 64 for reverse transcriptase (NtRTI group) and 16 (20%) of 79 for
integrase. Emergent resistance was associated with the raltegravir group (OR
2.47, 95% CI 1.02-5.99; p=0.05), baseline log10 viral load (1.83, 1.12-2.97;
p=0.02), and absence of the Lys65Arg (K65R) or Lys70Glu (K70E) mutation at
baseline (3.18, 1.12-9.02; p=0.03). INTERPRETATION: Poor adherence was a major
determinant of virological failure in people on second-line ART. In settings with
limited resources, investment in optimisation of adherence rather than
implementation of drug resistance testing might be advisable. FUNDING: University
of New South Wales Australia, Merck, AbbVie, and the Foundation for AIDS
Research.
PMID- 26424461
TI - Effects of statin therapy on coronary artery plaque volume and high-risk plaque
morphology in HIV-infected patients with subclinical atherosclerosis: a
randomised, double-blind, placebo-controlled trial.
AB - BACKGROUND: HIV-infected patients have a high risk of myocardial infarction. We
aimed to assess the ability of statin treatment to reduce arterial inflammation
and achieve regression of coronary atherosclerosis in this population. METHODS:
In a randomised, double-blind, placebo-controlled trial, 40 HIV-infected
participants with subclinical coronary atherosclerosis, evidence of arterial
inflammation in the aorta by fluorodeoxyglucose (FDG)-PET, and LDL-cholesterol
concentration of less than 3.37 mmol/L (130 mg/dL) were randomly assigned (1:1)
to 1 year of treatment with atorvastatin or placebo. Randomisation was by the
Massachusetts General Hospital (MGH) Clinical Research Pharmacy with a permuted
block algorithm, stratified by sex with a fixed block size of four. Study codes
were available only to the MGH Research Pharmacy and not to study investigators
or participants. The prespecified primary endpoint was arterial inflammation as
assessed by FDG-PET of the aorta. Additional prespecified endpoints were non
calcified and calcified plaque measures and high risk plaque features assessed
with coronary CT angiography and biochemical measures. Analysis was done by
intention to treat with all available data and without imputation for missing
data. The trial is registered with ClinicalTrials.gov, number NCT00965185.
FINDINGS: The study was done from Nov 13, 2009, to Jan 13, 2014. 19 patients were
assigned to atorvastatin and 21 to placebo. 37 (93%) of 40 participants completed
the study, with equivalent discontinuation rates in both groups. Baseline
characteristics were similar between groups. After 12 months, change in FDG-PET
uptake of the most diseased segment of the aorta was not different between
atorvastatin and placebo, but technically adequate results comparing longitudinal
changes in identical regions could be assessed in only 21 patients (atorvastatin
Delta -0.03, 95% CI -0.17 to 0.12, vs placebo Delta -0.06, -0.25 to 0.13;
p=0.77). Change in plaque could be assessed in all 37 people completing the
study. Atorvastatin reduced non-calcified coronary plaque volume relative to
placebo: median change -19.4% (IQR -39.2 to 9.3) versus 20.4% (-7.1 to 94.4;
p=0.009, n=37). The number of high-risk plaques was significantly reduced in the
atorvastatin group compared with the placebo group: change in number of low
attenuation plaques -0.2 (95% CI -0.6 to 0.2) versus 0.4 (0.0, 0.7; p=0.03;
n=37); and change in number of positively remodelled plaques -0.2 (-0.4 to 0.1)
versus 0.4 (-0.1 to 0.8; p=0.04; n=37). Direct LDL-cholesterol (-1.00 mmol/L, 95%
CI -1.38 to 0.61 vs 0.30 mmol/L, 0.04 to 0.55, p<0.0001) and lipoprotein
associated phospholipase A2 (-52.2 ng/mL, 95% CI -70.4 to -34.0, vs -13.3 ng/mL,
32.8 to 6.2; p=0.005; n=37) decreased significantly with atorvastatin relative to
placebo. Statin therapy was well tolerated, with a low incidence of clinical
adverse events. INTERPRETATION: No significant effects of statin therapy on
arterial inflammation of the aorta were seen as measured by FDG-PET. However,
statin therapy reduced non-calcified plaque volume and high-risk coronary plaque
features in HIV-infected patients. Further studies should assess whether
reduction in high-risk coronary artery disease translates into effective
prevention of cardiovascular events in this at-risk population. FUNDING: National
Institutes of Health, Harvard Clinical and Translational Science Center, National
Center for Research Resources.
PMID- 26424464
TI - Naturally together: pitch-height and brightness as coupled factors for eliciting
the SMARC effect in non-musicians.
AB - Pitch-height is often labeled spatially (i.e., low or high) as a function of the
fundamental frequency of the tone. This correspondence is highlighted by the so
called Spatial-Musical Association of Response Codes (SMARC) effect. However, the
literature suggests that the brightness of the tone's timbre might contribute to
this spatial association. We investigated the SMARC effect in a group of non
musicians by disentangling the role of pitch-height and the role of tone
brightness. In three experimental conditions, participants were asked to judge
whether the tone they were listening to was (or was not) modulated in amplitude
(i.e., vibrato). Participants were required to make their response in both the
horizontal and the vertical axes. In a first condition, tones varied coherently
in pitch (i.e., manipulation of the tone's F0) and brightness (i.e., manipulation
of the tone's spectral centroid); in a second condition, pitch-height varied
whereas brightness was fixed; in a third condition, pitch-height was fixed
whereas brightness varied. We found the SMARC effect only in the first condition
and only in the vertical axis. In contrast, we did not observe the effect in any
of the remaining conditions. The present results suggest that, in non-musicians,
the SMARC effect is not due to the manipulation of the pitch-height alone, but
arises because of a coherent change of pitch-height and brightness; this effect
emerges along the vertical axis only.
PMID- 26424465
TI - Rectal bleeding due to rectal erosion of vaginal mesh.
PMID- 26424466
TI - The LysR-type regulator LeuO regulates the acid tolerance response in Vibrio
cholerae.
AB - Vibrio cholerae is a neutrophilic enteric pathogen that is extremely sensitive to
acid. As V. cholerae passages through the host gastrointestinal tract it is
exposed to a variety of environmental stresses including low pH and volatile
fatty acids. Exposure to acidic environments induces expression of the V.
cholerae acid tolerance response. A key component of the acid tolerance response
is the cad system, which is encoded by cadC and the cadBA operon. CadB is a
lysine/cadaverine antiporter and CadA is a lysine decarboxylase and these
function together to counter low intracellular and extracellular pH. CadC is a
membrane-associated transcription factor that activates cadBA expression in
response to acidic conditions. Herein we investigated the role of the LysR-type
transcriptional regulator LeuO in the V. cholerae acid tolerance response.
Transcriptional reporter assays revealed that leuO expression repressed cadC
transcription, indicating that LeuO was a cadC repressor. Consistent with this,
leuO expression was inversely linked to lysine decarboxylase production and leuO
overexpression resulted in increased sensitivity to organic acids. Overexpression
of leuO in a cadA mutant potentiated killing by organic acids, suggesting that
the function of leuO in the acid tolerance response extended beyond its
regulation of the cad system. Collectively, these studies have identified a new
physiological role for LeuO in V. cholerae acid tolerance.
PMID- 26424467
TI - Recanalization of chronic total coronary occlusions--high success rate despite a
restrictive use of the retrograde approach.
AB - AIM: The retrograde approach in chronic total occlusion (CTO) percutaneous
coronary intervention (PCI) is increasingly being used as a first-line
intervention despite a higher radiation exposure, contrast volume, and a higher
major adverse cardiac event (MACE) rate compared with the antegrade approach. It
was aimed to evaluate the overall success rate of CTO-PCI over time when the
retrograde approach was restrictively used only after a failed antegrade attempt.
METHODS AND RESULTS: In a prospective single operator registry from January 2008
to December 2012 about 436 consecutive patients underwent a CTO-PCI. Mean age was
63.4 +/- 10.3 years, and 86% were male. The overall success rate improved
significantly over time [68% (first quartile) to 91% (fourth quartile), P <
0.001] due to a significant increase of the antegrade success rate. This could be
achieved by a retrograde approach of less than 20% with no change over time. The
overall in-hospital MACE rate was 0.69% with no difference between antegrade and
retrograde procedures. CONCLUSIONS: A high CTO-PCI success rate of above 90%
could be achieved with a restrictive use of the retrograde technique.
PMID- 26424468
TI - Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol in
rats-strain difference and antagonism by atipamezole.
AB - An anesthetic mixture of medetomidine (MED), midazolam (MID), and butorphanol
(BUT) has been used in laboratory animals. We previously reported that this
anesthetic mixture produced closely similar anesthetic effects in BALB/c and
C57BL/6J strains. We also demonstrated the efficacy of atipamezole (ATI), an
antagonist of MED that produced quick recovery from anesthesia in mice.
Anesthetics have various anesthetic effects among animal strains. However, the
differences in the effects of anesthetic mixtures in rats are unclear. In the
present study, we first examined effects of the abovementioned anesthetic mixture
using three different rat strains: Wistar (WST), Sprague-Dawley (SD), and Fischer
344 (F344). Second, we examined how different dosages and optimum injection
timing of ATI affected recovery from anesthesia in rats. We used the anesthetic
score to measure anesthetic duration and a pulse oximeter to monitor vital signs.
We found no significant differences in anesthetic duration among the three
different strains. However, recovery from anesthesia in the SD strain took
significantly longer than in the other strains. The antagonistic effects of ATI
(0.15 mg/kg and 0.75 mg/kg) were equivalent when administered at 30 min after
anesthetic mixture administration. The antagonistic effects of ATI 0.75 mg/kg
were stronger than those of ATI 0.15 mg/kg at 10 min after anesthetic mixture
administration. This anesthetic mixture is a useful drug that can induce similar
anesthetic effects in three different strains and has an antagonist, ATI, that
makes rats quickly recover from anesthesia. These results may contribute to the
welfare of laboratory animals.
PMID- 26424469
TI - Accelerated pathway evolution in mouse-like rodents involves cell cycle control.
AB - Rodents include both the cancer-susceptible short-lived mouse and the two
unrelated cancer-resistant long-lived mole-rats. In this work, their genomes were
analyzed with the goal to reveal pathways enriched in genes, which are more
similar between the mole-rats than between the mouse and the naked mole-rat. The
pathways related to cell cycle control were prominent. They include external
signal transduction and all cell cycle stages. There are several stem cell
pathways among them. The other enriched pathways involve ubiquitin-dependent
protein degradation, immunity, mRNA splicing, and apoptosis. The ubiquitin
dependent protein degradation is a core of network of enriched pathways. However,
this phenomenon is not specific for the mouse and the mole-rats. The other muroid
species show features similar to the mouse, whereas the non-muroid rodents and
the human show features similar to the mole-rats. The higher ratio of non
synonymous to synonymous nucleotide substitutions (dN/dS) indicates the
accelerated evolution of revealed pathways in the muroid rodents (except the
blind mole-rat). Paradoxically, the dN/dS averaged over the whole genome is lower
in the muroids, i.e., the purifying selection is generally stronger in them. In
practical sense, these data suggest caveat for using muroid rodents (mouse, rat,
and hamsters) as biomedical models of human conditions involving cell cycle and
show the network of pathways where muroid genes are most different (compared with
non-muroid) from human genes. The guinea pig is emphasized as a more suitable
rodent model for biomedical research involving cell cycle.
PMID- 26424470
TI - Relationships between self-reported lifetime physical activity, estimates of
current physical fitness, and aBMD in adult premenopausal women.
AB - Osteoporosis is common, and physical activity is important in its prevention and
treatment. Of the categories of historical physical activity (PA) examined, we
found that weight-bearing and very hard physical activity had the strongest
relationships with areal bone mineral density (aBMD) throughout growth and into
adulthood, while for measures of strength, only grip strength proved to be an
independent predictor of aBMD. PURPOSE/INTRODUCTION: To examine relationships
between aBMD (total body, lumbar spine, proximal femur, tibial shaft, distal
radius) and estimates of historical PA, current strength, and cardiovascular
fitness in adult premenopausal women. METHODS: One hundred fifty-two adult
premenopausal women (40 +/- 9.6 years) undertook aBMD (dual-energy X-ray
absorptiometry (DXA)) and completed surveys to estimate historical physical
activity representative of three decades (Kriska et al. [1]), while subsets
underwent functional tests of isokinetic strength (hamstrings and quadriceps),
grip strength (hand dynamometer), and maximum oxygen uptake (MaxV02; cycle
ergometer). Historical PA was characterized by demand (metabolic equivalents, PA
> 3 METS; PA > 7 METS) and type (weight-bearing; high impact). RESULTS:
Significant positive independent predictors varied by decade and site, with
weight-bearing exercise and PA > 3 METS significant for the tibial shaft (10-19
decade) and only PA > 7 METS significant for the final two decades (20-29 and 30
39 years; total body and total hip). A significant negative correlation between
high impact activity and tibial shaft aBMD appeared for the final decade. For
strength measures, only grip strength was an independent predictor (total body,
total hip), while MaxV02 provided a significant independent prediction for the
tibial shaft. CONCLUSIONS: Past PA > 7 METS was positively associated with aBMD,
and such activity should probably constitute a relatively high proportion of all
weekly PA to positively affect aBMD. The findings warrant more detailed
investigations in a prospective study, specifically also investigating the
potentially negative effects of high impact PA on tibial aBMD.
PMID- 26424471
TI - Factors impacting the quality of peer relationships of youth with Tourette's
syndrome.
AB - BACKGROUND: Tourette's syndrome (TS) is a poorly understood neurodevelopmental
disorder consistently associated with impaired peer relationships. This research
aimed to investigate the relationship between TS and the ability of diagnosed
youth to form secure attachment relationships with peers. A quantitative study
examined differences between youth with TS and typically developing peers in
social functioning, relationship problems and attachment security. Qualitative
studies sought to identify factors that enhanced or impeded the ability to form
secure peer relationships, including the impact of tic severity, comorbidity and
personality traits. All research was conducted from the parental perspective.
METHODS: The research consisted of a controlled, survey-based qualitative and
quantitative study (Study One) of parents of youth with TS (n = 86) and control
group peers (n = 108), and a qualitative telephone interview-based study of TS
group parents (Study Two, n = 22). Quantitative assessment of social functioning,
peer problems and peer attachment security was conducted using the Paediatric
Quality of Life inventory, the Strengths and Difficulties Questionnaire and the
Attachment Questionnaire for Children. Qualitative data relating to personality
was classified using the Five Factor Model. RESULTS: Results revealed
significantly higher rates of insecure peer attachment, problems in peer
relationships, difficulty making friends, stigmatisation and lower levels of
social functioning for the TS group. Significant between-group differences in
number and type of factors impacting peer relationships were also determined with
'personality' emerging as the most prevalent factor. Whilst Extraversion and
Agreeableness facilitated friendships for both groups, higher rates of
Neuroticism were barriers to friendship for individuals with TS. The TS group
also identified multiple 'non-personality' factors impacting peer relationships,
including TS and comorbid symptom severity, the child's psychological and
behavioural adjustment to their disorder, coping strategies and the behaviour and
attitudes of peers. DISCUSSION: Our findings suggest that, whilst Extraversion
and Agreeableness facilitated friendships for both groups, higher rates of
Neuroticism were barriers to friendship for individuals with TS. Notwithstanding
the fact that these findings are based on parental report and not the perceptions
of youth themselves, this study may help clinicians to identify youth at
increased risk of developing insecure peer relationships and guide the
development of targeted supports. CONCLUSIONS: The findings from the study may
help clinicians, parents and individuals with TS to better understand and cope
with the difficulties experienced in interactions with peers.
PMID- 26424472
TI - Response to commentary: Anomalous origin of the left pulmonary artery from the
internal carotid artery.
PMID- 26424473
TI - Utility and feasibility of integrating pulse oximetry into the routine assessment
of young infants at primary care clinics in Karachi, Pakistan: a cross-sectional
study.
AB - BACKGROUND: Hypoxemia may occur in young infants with severe acute illnesses or
congenital cardiac anomalies, but is not reliably detected on physical exam.
Pulse oximetry (PO) can be used to detect hypoxemia, but its application in low
income countries has been limited, and its feasibility in the routine assessment
of young infants (aged 0-59 days) has not been previously studied. The aim of
this study was to characterize the operational feasibility and parent/guardian
acceptability of incorporating PO into the routine clinical assessment of young
infants in a primary care setting in a low-income country. METHODS: This was a
cross-sectional study of 862 visits by 529 infants at two primary care clinics in
Karachi, Pakistan (March to June, 2013). After clinical assessment, oxygen
saturation (Sp02) was measured by a handheld PO device (Rad-5v, Masimo
Corporation) according to a standardized protocol. Performance time (PT) was the
time between sensor placement and attainment of an acceptable PO reading (i.e.,
stable SpO2 + 1% for at least 10 s, heart rate displayed, and adequate signal
indicators). PT included the time for one repeat attempt at a different
anatomical site if the first attempt did not yield an acceptable reading within 1
min. Parent/guardian acceptability of PO was based on a questionnaire and
unprompted comments about the procedure. All infants underwent physician
assessment. RESULTS: Acceptable PO readings were obtained in <= 1 and <= 5 min at
94.4% and 99.8% of visits, respectively (n = 862). Median PT was 42 s
(interquartile range 37; 50). Parents/guardians overwhelmingly accepted PO (99.6%
overall satisfaction, n = 528 first visits). Of 10 infants with at least one
visit with Sp02 <92% on a first PO attempt, 3 did not have a significant acute
illness on physician assessment. There were no PO-related adverse events.
DISCUSSION: Using a commercially available handheld pulse oximeter, acceptable
Sp02 measurements were obtained in nearly all infants in under 1 minute. The
procedure was readily integrated into existing assessment pathways and
parents/guardians had positive views of the technology. CONCLUSIONS: When
incorporated into routine clinical assessment of young infants at primary care
clinics in a low-income country, PO was feasible and acceptable to
parents/guardians. Future research is needed to determine if the introduction of
routine PO screening of young infants will improve outcomes in low-resource
settings.
PMID- 26424474
TI - Tissue-Engineered External Anal Sphincter Using Autologous Myogenic Satellite
Cells and Extracellular Matrix: Functional and Histological Studies.
AB - The aim of the present study was to demonstrate the regaining histological
characteristics of bioengineered external anal sphincters (EAS) in rabbit fecal
incontinence model. The EAS of 16 rabbits were resected and decellularized. The
decellularized scaffolds were transplanted to the terminal rectum following a
period of 6 months of fecal incontinency (5 days after sterilization). The
rabbits were divided into two groups: in group 1 (n = 8), myogenic satellite
cells were injected into the transplanted sphincters. In group 2 (n = 8), the
transplanted scaffolds remained in situ without cellular injection. The
histological evaluation was performed with desmin, myosin, smooth muscle actin,
CD31, and CD34 at 3-month intervals. The rabbits were followed for 2 years.
Electromyography (EMG) with needle and electrical stimulation, pudendal and
muscle electrical stimulation were also performed after 2 years of
transplantation. At the time of biopsy, no evidence of inflammation or rejection
was observed and the transplanted EAS appeared histologically and anatomically
normal. The immunohistochemistry staining validated that the histological
features of EAS was more satisfactory in group 1 in short-term follow-up.
However, no statistically significant difference was detected between two groups
in long-term follow-ups (p value > 0.05). In both groups, grafted EAS contracted
in response to electrical signals delivered to the muscle and the pudendal nerve.
However, more signals were detected in group 1 in EMG evaluation. In conclusion,
bioengineered EAS with myogenic satellite cells can gain more satisfactory
histological outcomes in short-term follow-ups with better muscle electrical
stimulation outcomes.
PMID- 26424475
TI - From Finite Element Meshes to Clouds of Points: A Review of Methods for
Generation of Computational Biomechanics Models for Patient-Specific
Applications.
AB - It has been envisaged that advances in computing and engineering technologies
could extend surgeons' ability to plan and carry out surgical interventions more
accurately and with less trauma. The progress in this area depends crucially on
the ability to create robustly and rapidly patient-specific biomechanical models.
We focus on methods for generation of patient-specific computational grids used
for solving partial differential equations governing the mechanics of the body
organs. We review state-of-the-art in this area and provide suggestions for
future research. To provide a complete picture of the field of patient-specific
model generation, we also discuss methods for identifying and assigning patient
specific material properties of tissues and boundary conditions.
PMID- 26424476
TI - Image-Based Personalization of Cardiac Anatomy for Coupled Electromechanical
Modeling.
AB - Computational models of cardiac electromechanics (EM) are increasingly being
applied to clinical problems, with patient-specific models being generated from
high fidelity imaging and used to simulate patient physiology, pathophysiology
and response to treatment. Current structured meshes are limited in their ability
to fully represent the detailed anatomical data available from clinical images
and capture complex and varied anatomy with limited geometric accuracy. In this
paper, we review the state of the art in image-based personalization of cardiac
anatomy for biophysically detailed, strongly coupled EM modeling, and present our
own tools for the automatic building of anatomically and structurally accurate
patient-specific models. Our method relies on using high resolution unstructured
meshes for discretizing both physics, electrophysiology and mechanics, in
combination with efficient, strongly scalable solvers necessary to deal with the
computational load imposed by the large number of degrees of freedom of these
meshes. These tools permit automated anatomical model generation and strongly
coupled EM simulations at an unprecedented level of anatomical and biophysical
detail.
PMID- 26424478
TI - The spectrum of expert reports on clinical biochemical toxicology and medicine
from an Irish practice.
AB - The compounds which generated an expert opinion report in the area of medical
toxicology in the period 1999 to 2015 are presented from the toxicological case
files of a specialist in chemical pathology and general internal medicine. There
were 132 different compounds from 86 cases. Alcohol was involved in 43%, drugs of
abuse in 18.6%, volatile carbon compounds in 17.4%, metals in 9.3%, and carbon
monoxide in 4.6%. Many compounds appeared once. The duty of the medical expert
witness to provide an objective report for the court irrespective of the payer is
stated. The addition of references from peer reviewed literature to substantiate
the pros and cons of each case is recommended as a standard operating procedure
in completing each report.
PMID- 26424479
TI - Non-vehicular homicides masquerading as road traffic accidents.
AB - Interfering with or planting evidence to disguise the cause of a death is not
uncommon in forensic practice. Homicides staged as road accidents are, however,
rarely encountered by crime scene investigators. We report two homicides which
were presented as road traffic accidents. Case 1: Dead body of a 35-year-old male
was brought for autopsy with history of road traffic accident. Primary police
inquiry suggested that the victim was knocked down by a speeding four-wheeler,
while walking by the side of a high way with his friends. On postmortem
examination the deceased's death was found due to homicidal smothering staged as
a road traffic accident. Case 2: Dead body of 40-year-old male was brought for
autopsy with history of road traffic accident. It was an unwitnessed crush by a
speeding four-wheeler. However, on postmortem examination, the deceased was found
to have died from homicidal multiple stab wounds with his death staged as a road
traffic accident. Importance of meticulous autopsy to determine accurately the
cause of death is emphasized.
PMID- 26424477
TI - Effects of different arachidonic acid supplementation on psychomotor development
in very preterm infants; a randomized controlled trial.
AB - BACKGROUND & AIMS: Nutritional supplementation with polyunsaturated fatty acids
is important in preterm infants neurodevelopment, but it is not known if the
omega-6/omega-3 ratio affects this process. This study was designed to determine
the effects of a balanced contribution of arachidonic acid in very preterm
newborns fed with formula milk. METHODS: This was a randomized trial, in which
newborns <1500 g and/or <32 weeks gestational age were assigned to one of two
groups, based on the milk formula they would receive during the first year of
life. Initially, 60 newborns entered the study, but ultimately, group A was
composed of 24 newborns, who were given formula milk with an omega-6/omega-3
ratio of 2/1, and Group B was composed of 21 newborns, given formula milk with an
omega-6/omega-3 ratio of 1/1. The infants were followed up for two years: growth,
visual-evoked potentials, brainstem auditory-evoked potentials, and plasma fatty
acids were periodically measured, and psychomotor development was assessed using
the Brunet Lezine scale at 24 months corrected age. A control group, for
comparison of Brunet Lezine score, was made up of 25 newborns from the SEN1500
project, who were fed exclusively with breast milk. RESULTS: At 12 months,
arachidonic acid values were significantly higher in group A than in group B
(6.95 +/- 1.55% vs. 4.55 +/- 0.78%), as were polyunsaturated fatty acids (41.02
+/- 2.09% vs. 38.08 +/- 2.32%) achieved a higher average. Group A achieved a
higher average Brunet Lezine score at 24 months than group B (99.9 +/- 9 vs. 90.8
+/- 11, p =0.028). The Brunet Lezine results from group A were compared with the
control group results, with very similar scores registered between the two groups
(99.9 +/- 9 vs. 100.5 +/- 7). There were no significant differences in growth or
evoked potentials between the two formula groups. CONCLUSIONS: Very preterm
infants who received formula with an omega-6/omega-3 ratio of 2/1 had higher
blood levels of essential fatty acids during the first year of life, and better
psychomotor development, compared with very preterm newborns who consumed formula
with an omega-6/omega-3 of 1/1. Therefore, formula milk with an arachidonic acid
quantity double that of docosahexaenoic acid should be considered for feeding
very preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier
NCT02503020.
PMID- 26424480
TI - Chronic mercury exposure in Late Neolithic/Chalcolithic populations in Portugal
from the cultural use of cinnabar.
AB - Cinnabar is a natural mercury sulfide (HgS) mineral of volcanic or hydrothermal
origin that is found worldwide. It has been mined prehistorically and
historically in China, Japan, Europe, and the Americas to extract metallic
mercury (Hg(0)) for use in metallurgy, as a medicinal, a preservative, and as a
red pigment for body paint and ceramics. Processing cinnabar via combustion
releases Hg(0) vapor that can be toxic if inhaled. Mercury from cinnabar can also
be absorbed through the gut and skin, where it can accumulate in organs and bone.
Here, we report moderate to high levels of total mercury (THg) in human bone from
three Late Neolithic/Chalcolithic (5400-4100 B.P.) sites in southern Portugal
that were likely caused by cultural use of cinnabar. We use light stable isotope
and Hg stable isotope tracking to test three hypotheses on the origin of mercury
in this prehistoric human bone. We traced Hg in two individuals to cinnabar
deposits near Almaden, Spain, and conclude that use of this mineral likely caused
mild to severe mercury poisoning in the prehistoric population. Our methods have
applications to bioarchaeological investigations worldwide, and for tracking
trade routes and mobility of prehistoric populations where cinnabar use is
documented.
PMID- 26424481
TI - Ciliary subcompartments and cysto-proteins.
AB - Renal cystic diseases are conditions in which parts of or entire nephrons become
enlarged and create fluid-filled cysts. These cysts occur in many genetic
diseases. Most of the products of causative genes, termed cysto-proteins, are
localized in cilia and/or centrioles. In addition, mutant mice lacking cilia
develop renal cysts. Therefore, cilia are thought to have an important role in
renal cystogenesis. The cilium is a tiny projection from the cell surface;
however, it can be divided into several subcompartments. These subcompartments
have specific roles. This review attempts to classify cysto-proteins based on
their localization in ciliary subcompartments with the aim of defining
relationships among them and of identifying their exact intraciliary functions.
PMID- 26424482
TI - A Chlamydia trachomatis strain with a chemically generated amino acid
substitution (P370L) in the cthtrA gene shows reduced elementary body production.
AB - BACKGROUND: Chlamydia (C.) trachomatis is the most prevalent bacterial sexually
transmitted infection worldwide and the leading cause of preventable blindness.
Genetic approaches to investigate C. trachomatis have been only recently
developed due to the organism's intracellular developmental cycle. HtrA is a
critical stress response serine protease and chaperone for many bacteria and in
C. trachomatis has been previously shown to be important for heat stress and the
replicative phase of development using a chemical inhibitor of the CtHtrA
activity. In this study, chemically-induced SNVs in the cthtrA gene that resulted
in amino acid substitutions (A240V, G475E, and P370L) were identified and
characterized. METHODS: SNVs were initially biochemically characterized in vitro
using recombinant protein techniques to confirm a functional impact on
proteolysis. The C. trachomatis strains containing the SNVs with marked
reductions in proteolysis were investigated in cell culture to identify
phenotypes that could be linked to CtHtrA function. RESULTS: The strain harboring
the SNV with the most marked impact on proteolysis (cthtrA P370L) was detected to
have a significant reduction in the production of infectious elementary bodies.
CONCLUSIONS: This provides genetic evidence that CtHtrA is critical for the C.
trachomatis developmental cycle.
PMID- 26424483
TI - Understanding and predicting binding between human leukocyte antigens (HLAs) and
peptides by network analysis.
AB - BACKGROUND: As the major histocompatibility complex (MHC), human leukocyte
antigens (HLAs) are one of the most polymorphic genes in humans. Patients
carrying certain HLA alleles may develop adverse drug reactions (ADRs) after
taking specific drugs. Peptides play an important role in HLA related ADRs as
they are the necessary co-binders of HLAs with drugs. Many experimental data have
been generated for understanding HLA-peptide binding. However, efficiently
utilizing the data for understanding and accurately predicting HLA-peptide
binding is challenging. Therefore, we developed a network analysis based method
to understand and predict HLA-peptide binding. METHODS: Qualitative Class I HLA
peptide binding data were harvested and prepared from four major databases. An
HLA-peptide binding network was constructed from this dataset and modules were
identified by the fast greedy modularity optimization algorithm. To examine the
significance of signals in the yielded models, the modularity was compared with
the modularity values generated from 1,000 random networks. The peptides and HLAs
in the modules were characterized by similarity analysis. The neighbor-edges
based and unbiased leverage algorithm (Nebula) was developed for predicting HLA
peptide binding. Leave-one-out (LOO) validations and two-fold cross-validations
were conducted to evaluate the performance of Nebula using the constructed HLA
peptide binding network. RESULTS: Nine modules were identified from analyzing the
HLA-peptide binding network with a highest modularity compared to all the random
networks. Peptide length and functional side chains of amino acids at certain
positions of the peptides were different among the modules. HLA sequences were
module dependent to some extent. Nebula archived an overall prediction accuracy
of 0.816 in the LOO validations and average accuracy of 0.795 in the two-fold
cross-validations and outperformed the method reported in the literature.
CONCLUSIONS: Network analysis is a useful approach for analyzing large and sparse
datasets such as the HLA-peptide binding dataset. The modules identified from the
network analysis clustered peptides and HLAs with similar sequences and
properties of amino acids. Nebula performed well in the predictions of HLA
peptide binding. We demonstrated that network analysis coupled with Nebula is an
efficient approach to understand and predict HLA-peptide binding interactions and
thus, could further our understanding of ADRs.
PMID- 26424484
TI - Hierarchical ferroelectric and ferrotoroidic polarizations coexistent in nano
metamaterials.
AB - Tailoring materials to obtain unique, or significantly enhanced material
properties through rationally designed structures rather than chemical
constituents is principle of metamaterial concept, which leads to the realization
of remarkable optical and mechanical properties. Inspired by the recent progress
in electromagnetic and mechanical metamaterials, here we introduce the concept of
ferroelectric nano-metamaterials, and demonstrate through an experiment in silico
with hierarchical nanostructures of ferroelectrics using sophisticated real-space
phase-field techniques. This new concept enables variety of unusual and complex
yet controllable domain patterns to be achieved, where the coexistence between
hierarchical ferroelectric and ferrotoroidic polarizations establishes a new
benchmark for exploration of complexity in spontaneous polarization ordering. The
concept opens a novel route to effectively tailor domain configurations through
the control of internal structure, facilitating access to stabilization and
control of complex domain patterns that provide high potential for novel
functionalities. A key design parameter to achieve such complex patterns is
explored based on the parity of junctions that connect constituent
nanostructures. We further highlight the variety of additional functionalities
that are potentially obtained from ferroelectric nano-metamaterials, and provide
promising perspectives for novel multifunctional devices. This study proposes an
entirely new discipline of ferroelectric nano-metamaterials, further driving
advances in metamaterials research.
PMID- 26424485
TI - Improvement of an enzyme-linked immunosorbent assay for equine herpesvirus type 4
by using a synthetic-peptide 24-mer repeat sequence of glycoprotein G as an
antigen.
AB - To increase the sensitivity of an enzyme-linked immunosorbent assay (ELISA) for
equine herpesvirus type 4 (EHV-4) that uses a 12-mer peptide of glycoprotein G
(gG4-12-mer: MKNNPIYSEGSL) [4], we used a longer peptide consisting of a 24-mer
repeat sequence (gG4-24-mer: MKNNPIYSEGSLMLNVQHDDSIHT) as an antigen. Sera of
horses experimentally infected with EHV-4 reacted much more strongly to the gG4
24-mer peptide than to the gG4-12-mer peptide. We used peptide ELISAs to test
paired sera from horses naturally infected with EHV-4 (n=40). gG4-24-mer ELISA
detected 37 positive samples (92.5%), whereas gG4-12-mer ELISA detected only 28
(70.0%). gG4-24-mer ELISA was much more sensitive than gG4-12-mer ELISA.
PMID- 26424486
TI - Three questions about study on treatments for pyoderma gangrenosum.
PMID- 26424488
TI - Ultralow temperature terahertz magnetic thermodynamics of perovskite-like SmFeO3
ceramic.
AB - The terahertz magnetic properties of perovskite-like SmFeO3 ceramic are
investigated over a broad temperature range, especially at ultralow temperatures,
using terahertz time-domain spectroscopy. It is shown that both resonant
frequencies of quasi-ferromagnetic and quasi-antiferromagnetic modes have blue
shifts with the decreasing temperature due to the enhancement of effective
magnetic field. The temperature-dependent magnetic anisotropy constants are
further estimated using the resonant frequencies, under the approximation of
omitting the contribution of Sm(3+) magnetic moments to the effective field.
Specially, the effective anisotropy constants in the ca and cb planes at 3 K are
6.63 * 10(5) erg/g and 8.48 * 10(5) erg/g, respectively. This thoroughly reveals
the terahertz magnetic thermodynamics of orthoferrites and will be beneficial to
the application in terahertz magnetism.
PMID- 26424487
TI - Percutaneous ablation therapies of inoperable pancreatic cancer: a systematic
review.
AB - Initial studies about ablation therapies of the pancreas were associated with
significant morbidity and mortality, which limited widespread adoption.
Development of techniques with high quality imaging used as guidance improve
outcomes reducing complications. Moreover, only few experiences of percutaneous
pancreatic ablations are reported. They are performed by very skilled operators
in highly specialized centers. This review presents the current status of
percutaneous local ablative therapies in the treatment of advanced pancreatic
cancer.
PMID- 26424489
TI - Conceptualization in pigeons: The evolution of a paradigm.
AB - Keller and Schoenfeld (1950) proposed a unique behavioral perspective on
conceptualization. They suggested that concepts refer solely to an organism's
behavior and to the conditions under which it occurs; as such, conceptual
behavior need be neither verbal nor uniquely human. Herrnstein and Loveland
(1964) advanced that behavioral perspective by deploying an elegant training
procedure to teach visual concepts to pigeons. Keller and Schoenfeld's
perspective and Herrnstein and Loveland's methodology have inspired my own
research into conceptualization by pigeons. Using a system of arbitrary visual
tokens, my colleagues and I have built ever-expanding nonverbal "vocabularies" in
pigeons through a variety of different concept learning tasks. Pigeons have
reliably categorized as many as 2000 individual photographs from as many as 16
different human object categories, even without the benefit of seeing an item
twice. Our formal model of conceptualization effectively embraces 25 years of
empirical evidence as well as generates novel predictions for both pigeon and
human conceptual behavior. Comparative study should continue to elucidate the
commonalities and disparities between human and nonhuman conceptual behavior; it
should also explicate the relationship between associative learning, object
recognition, conceptualization, and language.
PMID- 26424490
TI - The problem with categorical thinking by psychologists.
AB - Continua abound in the natural world, but the treatment of these continua in the
psychological study of behavior is often categorical. Four practices and their
consequences are considered: limited sampling of a continuum, turning continuous
predictors into categories through dichotomization and similar practices,
treating continuous predictors as categorical in an analysis, and overuse of the
analysis of variance. Concrete examples illustrate the consequences of these
practices. Recommendations to improve the treatment of continua, both in the
design and analysis of data, are provided.
PMID- 26424491
TI - Prognostic evaluation in obese patients using a dedicated multipinhole cadmium
zinc telluride SPECT camera.
AB - The purpose of this study is to evaluate the prognostic value of myocardial
perfusion SPECT obtained in CZT cameras (CZT-SPECT) with multipinhole collimation
in obese patients. CZT-SPECT may be technically challenging in the obese, and its
prognostic value remains largely unknown. Patients underwent single-day,
rest/stress (supine and prone) imaging. Images were visually inspected and graded
as poor, fair or good/excellent. Summed stress and difference scores (SSS and
SDS, respectively) were converted into percentages of total perfusion defect and
of ischemic defect by division by the maximum possible score. Obesity was defined
as a body mass index (BMI) >= 30 kg/m(2) and classified as class I (BMI 30-34.9
kg/m(2)), II (BMI 35-39.9 kg/m(2)), or III (BMI >= 40 kg/m(2)). Patients were
followed-up by telephone interview for the occurrence of all-cause death,
myocardial infarction or revascularization. A Cox proportional hazards analysis
was used to assess the independent predictors of death. Among 1396 patients, 365
(26.1 %) were obese (mean BMI 33.9 +/- 3.6; 17.5 % class I, 3.4 % class II, and
3.4 % class III). Image quality was good/excellent in 94.5 % of the obese
patients. The annualized mortality rates were not significantly different among
obese and non-obese patients, being <1 % with normal CZT-SPECT, and increased
with the degree of scan abnormality in both obese and non-obese patients. Age,
the use of pharmacologic stress and an abnormal CZT-SPECT, but not obesity, were
independent predictors of death. In obese patients, single-day rest/stress CZT
SPECT with a multipinhole camera provides prognostic discrimination with high
image quality.
PMID- 26424492
TI - 3D-Dixon MRI based volumetry of peri- and epicardial fat.
AB - There is growing evidence that pericardial and epicardial fat volume (PFV, EFV)
are associated with cardiovascular risk. We evaluated a novel method for accurate
measurement of PFV and EFV using a 3D-Dixon based cardiac magnetic resonance
(CMR) approach. An electrocardiography triggered and respiratory navigator gated
3D-gradient echo pulse sequence was used for cardiac Dixon imaging. Based on this
sequence, voxels predominantly containing fat were identified and added up for
volumetry. After accuracy assessment in phantoms, consisting of muscle tissue and
seven different fat samples (50-200 ml), the sequence was acquired in 34 healthy
volunteers (22 male, BMI range 14-42 kg/m(2), age range 21-79 years) at 1.5 T.
Analysis was performed independently by two readers who draw two 3D-regions of
interest, one for EFV and one for PFV. Additionally, EFV and PFV were compared
between overweighted and non-overweighted subjects. The phantom study showed an
excellent agreement of measured and true fat volumes (maximum difference = 6 %,
linear correlation coefficient R = 1.00). PFV over all volunteers was 158.0 +/-
126.4 ml and EFV was 77.0 +/- 55.3 ml. PFV and EFV were highly correlated (R =
0.96). Inter-reader agreement was good with a mean difference of 0.2 +/- 5.6 and
4.5 +/- 4.2 ml for PFV/EFV, (R > 0.99, each). EFV and PFV differed significantly
between subjects with BMI > 25 kg/m(2) and BMI < 25 kg/m(2), n = 17 each (PFV
219.0 +/- 151.8 vs. 96.9 +/- 44.7 ml and EFV 102.3 +/- 66.3 vs. 51.7 +/- 23.6 ml,
p < 0.001, each). The proposed 3D-Dixon based method allows accurate measurement
of cardiac fat volumes. It provides a valuable tool for cardiovascular risk
stratification by CMR.
PMID- 26424493
TI - Lipomatous hypertrophy of the right ventricle and interventricular septum
associated with ventricular arrhythmia.
PMID- 26424494
TI - Rebranding public health as "soft healing" is not necessary.
PMID- 26424495
TI - PAX3 and PAX7 as upstream regulators of myogenesis.
AB - Like other subclasses within the PAX transcription factor family, PAX3 and PAX7
play important roles in the emergence of a number of different tissues during
development. PAX3 regulates neural crest and, together with its orthologue PAX7,
is also expressed in parts of the central nervous system. In this chapter we will
focus on their role in skeletal muscle. Both factors are key regulators of
myogenesis where Pax3 plays a major role during early skeletal muscle formation
in the embryo while Pax7 predominates during post-natal growth and muscle
regeneration in the adult. We review the expression and functions of these
factors in the myogenic context. We also discuss mechanistic aspects of PAX3/7
function and modulation of their activity by interaction with other proteins, as
well as the post-transcriptional and transcriptional regulation of their
expression.
PMID- 26424496
TI - Age-associated changes in regenerative capabilities of mesenchymal stem cell:
impact on chronic wounds repair.
AB - Mesenchymal stem cells (MSCs) represent an ideal source of autologous cell-based
therapy for chronic wounds. Functional characteristics of MSCs may benefit wound
healing by exerting their multi-regenerative potential. However, cell ageing
resulting from chronic degenerative diseases or donor age could cause inevitable
effects on the regenerative abilities of MSCs. A variety of studies have shown
the relationship between MSC ageing and age-related dysfunction, but few
associate these age-related impacts on MSCs with their ability of repairing
chronic wounds, which are common in the elderly population. Here, we discuss the
age-associated changes of MSCs and describe the potential impacts on MSC-based
therapy for chronic wounds. Furthermore, critical evaluation of the current
literatures is necessary for understanding the underlying mechanisms of MSC
ageing and raising the corresponding concerns on considering their possible use
for chronic wound repair.
PMID- 26424497
TI - Association between use of proton pump inhibitors and non-typhoidal salmonellosis
identified following investigation into an outbreak of Salmonella Mikawasima in
the UK, 2013.
AB - In November 2013, national public health agencies in England and Scotland
identified an increase in laboratory-confirmed Salmonella Mikawasima. The role of
proton pump inhibitors (PPIs) as a risk factor for salmonellosis is unclear; we
therefore captured information on PPI usage as part of our outbreak
investigation. We conducted a case-control study, comparing each case with two
controls. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were
estimated using multivariable logistic regression. Thirty-nine of 61 eligible
cases were included in the study. The median age of cases was 45 years; 56% were
female. Of these, 33% were admitted to hospital and 31% reported taking PPIs. We
identified an association between PPIs and non-typhoidal salmonellosis (aOR 8.8,
95% CI 2.0-38.3). There is increasing evidence supporting the existence of an
association between salmonellosis and PPIs; however, biological studies are
needed to understand the effect of PPIs in the pathogenesis of Salmonella. We
recommend future outbreak studies investigate PPI usage to strengthen evidence on
the relevance of PPIs in Salmonella infection. These findings should be used to
support the development of guidelines for patients and prescribers on the risk of
gastrointestinal infection and PPI usage.
PMID- 26424498
TI - Giant Optical Activity of Quantum Dots, Rods, and Disks with Screw Dislocations.
AB - For centuries mankind has been modifying the optical properties of materials:
first, by elaborating the geometry and composition of structures made of
materials found in nature, later by structuring the existing materials at a scale
smaller than the operating wavelength. Here we suggest an original approach to
introduce optical activity in nanostructured materials, by theoretically
demonstrating that conventional achiral semiconducting nanocrystals become
optically active in the presence of screw dislocations, which can naturally
develop during the nanocrystal growth. We show the new properties to emerge due
to the dislocation-induced distortion of the crystal lattice and the associated
alteration of the nanocrystal's electronic subsystem, which essentially modifies
its interaction with external optical fields. The g-factors of intraband
transitions in our nanocrystals are found comparable with dissymmetry factors of
chiral plasmonic complexes, and exceeding the typical g-factors of chiral
molecules by a factor of 1000. Optically active semiconducting nanocrystals-with
chiral properties controllable by the nanocrystal dimensions, morphology,
composition and blending ratio-will greatly benefit chemistry, biology and
medicine by advancing enantiomeric recognition, sensing and resolution of chiral
molecules.
PMID- 26424499
TI - Man and VAD: Deus Ex Machina.
PMID- 26424500
TI - Renoprotective effects of continuous positive airway pressure in chronic kidney
disease patients with sleep apnea.
AB - PURPOSE: Chronic kidney disease (CKD) is associated with a high incidence of
obstructive sleep apnea (OSA). We assessed the effect of continuous positive
airway pressure (CPAP) on renal function in patients with CKD and OSA. METHODS:
In this retrospective cohort study, 42 patients with Stage 3-5 CKD and OSA were
stratified into two groups: patients who use CPAP more (average >4 h/night on >70
% of nights) and patients who use CPAP less (average <=4 h/night on <=70 % of
nights). Median follow-up time was 2.3 (1.6-2.9) years for greater and 2.0 (0.6
3.5) years for lesser CPAP users. Chart reviews were carried out to record
clinical characteristics, proteinuria measurements by urine dipstick, and eGFR
values calculated by CKD-EPI equations. Univariate analyses were performed using
Wilcoxon rank-sum and Kruskal-Wallis tests. Multivariate logistic regression
models were applied to assess eGFR decline after CPAP prescription. RESULTS:
Twelve (29 %) of the 42 subjects used CPAP more. Groups were similar with respect
to age, body mass index, blood pressure, Charlson Comorbidity Index, and baseline
eGFR and proteinuria. The median rate of decline of eGFR was significantly slower
at -0.07 mL/min/1.73 m(2)/year (range -30 to 13) in those who used more CPAP
compared to those who used it less at -3.15 mL/min/1.73 m(2)/year (range -27 to
7) (p = 0.027).Greater use of CPAP was also associated with a significantly
reduced level of proteinuria at 0.15 (range 0.0-3.0) versus 0.70 g/L (range 0.0
3.0) (p = 0.046). Less compliant CPAP users were more likely to have progressive
decline of eGFR (decline >3 mL/min/1.73 m(2)/year), with unadjusted OR 5.0 (95 %
CI 0.93-26.8) and adjusted OR 8.9 (95 % CI 1.1-72.8), adjusting for CCI and
baseline eGFR. CONCLUSIONS: Compliance to CPAP therapy is associated with a
slower rate of progression of CKD in patients with CKD and OSA.
PMID- 26424501
TI - The Clinical Outcome of Hypofractionated Stereotactic Radiotherapy With
CyberKnife Robotic Radiosurgery for Perioptic Pituitary Adenoma.
AB - Stereotactic radiation technique including single fraction radiosurgery and
conventional fractionated stereotactic radiotherapy is widely reported as an
effective treatment of pituitary adenomas. Because of the restricted radiation
tolerance dose of the optic pathway, single fraction radiosurgery has been
accepted for small tumor located far away from the optic apparatus, while
fractionated stereotactic radiotherapy may be suitable for larger tumor located
close to the optic pathway. More recently, hypofractionated stereotactic
radiotherapy has become an alternative treatment option that provides high rate
of tumor control and visual preservation for the perioptic lesions within 2 to 3
mm of the optic pathway. The objective of the study was to analyze the clinical
outcomes of perioptic pituitary adenomas treated with hypofractionated
stereotactic radiotherapy. From 2009 to 2012, 40 patients with perioptic
pituitary adenoma were treated with CyberKnife robotic radiosurgery. The median
tumor volume was 3.35 cm3 (range, 0.82-25.86 cm3). The median prescribed dose was
25 Gy (range, 20-28 Gy) in 5 fractions (range, 3-5). After the median follow-up
time of 38.5 months (range, 14-71 months), 1 (2.5%) patient with prolactinoma had
tumor enlargement, 31 (77.5%) were stable, and the remaining 8 (20%) tumors were
smaller in size. No patient's vision deteriorated after hypofractionated
stereotactic radiotherapy. Hormone normalization was observed in 7 (54%) of 13
patients. No newly developed hypopituitarism was detected in our study. These
data confirmed that hypofractionated stereotactic radiotherapy achieved high
rates of tumor control and visual preservation. Because of the shorter duration
of treatment, it may be preferable to use hypofractionated stereotactic
radiotherapy over fractionated stereotactic radiotherapy for selected pituitary
adenomas immediately adjacent to the optic apparatus.
PMID- 26424502
TI - Stereotactic Radiotherapy in the Retreatment of Recurrent Cervical Cancers,
Assessment of Toxicity, and Treatment Response: Initial Results and Literature
Review.
AB - AIM: To evaluate the role of stereotactic body radiation therapy in the
retreatment of locally recurrent cervical cancers. Brachytherapy is the main
choice to treat gynecologic cancers. METHODS: Patients with recurrent cervical
cancer, previously submitted to radiotherapy, were treated with stereotactic body
radiation therapy using a CyberKnife system (Accuray Incorporated, Sunnyvale,
California) with a fiducial tracking system. RESULTS: From August 2011 to October
2014, 5 patients have been treated. Median age was 81 years (range, 70-84 years).
Two patients were diagnosed with adenocarcinoma endometrioid and 3 with squamous
cell carcinoma. Toxicity was scored according to the Radiation Therapy Oncology
Group/European Organization for Research and Treatment of Cancer criteria. After
a median follow-up of 12 months (range, 8-34 months), no severe (>grade 3)
acute/late genitourinary or low gastrointestinal toxicity was observed.
CONCLUSION: Our preliminary results of stereotactic body radiation therapy
"simulating" high dose rate for recurrent cervical cancers confirm a minimal
toxicity and an optimal outcome. The stereotactic body radiation therapy is an
alternative to high dose rate brachytherapy for gynecologic tumors.
PMID- 26424503
TI - Dynamical preparation of Floquet Chern insulators.
AB - Realizing topological insulators is of great current interest because of their
remarkable properties and possible future applications. There are recent
proposals based on Floquet analyses that one can generate topologically non
trivial insulators by periodically driving topologically trivial ones. Here we
address what happens if one follows the dynamics in such systems. Specifically,
we present an exact study of the time evolution of a graphene-like system
subjected to a circularly polarized electric field. We prove that for infinite
(translationally invariant) systems the Chern number is conserved under unitary
evolution. For systems with boundaries, on the other hand, we show that a
properly defined topological invariant, the Bott index, can change. Hence, it
should be possible to experimentally prepare topological states starting from non
topological ones. We show that the chirality of the edge current in such systems
can be controlled by adjusting the filling.
PMID- 26424504
TI - No weak days? Impact of day in the week on surgical mortality.
AB - BACKGROUND: Studies show increased rates of mortality for admissions on the
weekend (WE) versus the weekday (WD). However, scepticism exists of this so
called 'weekend effect' on patient outcome. It remains poorly investigated,
particularly the timing of the day of surgery and post-operative outcomes. A UK
study found higher odds of death when operated on Friday and the WE, versus WD.
This relationship was investigated by interrogating the Australian and New
Zealand Audit of Surgical Mortality database. METHODS: A standardized tool is
used to collect data after every surgical death. Data in this retrospective
cohort study from participating private and public hospitals in Australia on
elective and emergency operations were extracted and included 7718 patients who
had a surgical procedure within 30 days of admission and who subsequently died. A
proxy measure of early surgical mortality, namely odds of dying within the first
48 h following surgery, was used to compare surgical mortality across days of the
week. RESULTS: Unadjusted and adjusted odds of early surgical mortality were
higher on the WE compared to WD, unadjusted and adjusted OR 1.30 (P < 0.001) and
1.19 (P = 0.026), respectively. When separated by day of week, there was a trend
for higher surgical mortality on Friday, Saturday and Sunday versus all other
days, although this did not reach statistical significance. ASA grade and
specialty of surgery were important predictors of outcome. CONCLUSION: There
appears to be an association between day of surgery and surgical outcome. The
exact cause and contributing factors requires further investigation.
PMID- 26424506
TI - A zinc fixative for 3D visualization of cerebral capillaries and pericytes.
AB - BACKGROUND: A large volume of data indicates that disturbances in the morphology
and function of the capillary wall may play a causal role in several types of
neurodegenerative disorders. We present a highly reproducible staining method for
investigating the cerebral capillary network and the pericyte cells within the
basement membrane in mice - a specie specific challenging task when uniform
staining in thick sections was needed for confocal microscopy or a quantitative
analysis, e.g. stereological investigation using 3D probes. NEW METHOD: We
perfused C57BL6/Jbom mice and immersion fixated the brains with an aldehyde free
zinc fixative, which is normally used for paraffin embedded tissues, and stained
for CD31 and Collagen Type IV positive capillaries in 100MUm thick sections.
RESULTS: Using the milder zinc fixative allowed complete immunohistochemical
visualization of the cerebral capillary network in 100MUm thick sections using
CD31 or Collagen Type IV antibodies. Moreover CD31 or Collagen Type IV staining
revealed the presence of pericytes, which was confirmed by a fluorescent co
localization with the NG2 pericyte marker. COMPARISON WITH EXISTING METHODS:
Compared with conventional aldehyde-based fixative, this method resulted in a
homogeneous staining through the entire depth of thick sections with very limited
background staining and well-preserved morphology. CONCLUSIONS: This method is
suitable for 3D stereological analysis of capillary networks and pericytes within
thick brain sections using CD31 or Collagen Type IV antibodies.
PMID- 26424505
TI - High rates of unplanned interruptions from HIV care early after antiretroviral
therapy initiation in Nigeria.
AB - BACKGROUND: Unplanned care interruption (UCI) challenges effective HIV treatment.
We determined the frequency and risk factors for UCI in Nigeria. METHODS: We
conducted a retrospective-cohort study of adults initiating antiretroviral
therapy (ART) between January 2009 and December 2011. At censor, patients were
defined as in care, UCI, or inactive. Associations between baseline factors and
UCI rates were quantified using Poisson regression. RESULTS: Among 2,496
patients, 44 % remained in care, 35 % had >=1 UCI, and 21 % became inactive. UCI
rates were higher in the first year on ART (39/100PY), than the second
(19/100PY), third (16/100PY), and fourth (14/100PY) years (p < 0.001). In
multivariate analysis, baseline CD4 > 350/uL (IRR 3.21, p < 0.0001), being a
student (IRR 1.95, p < 0.0001), and less education (IRR 1.58, p = 0.001)
increased risk for UCI. Fifty-five percent of patients with UCI and viral load
data had HIV viral load > 1,000 copies/ml upon return to care. DISCUSSION: UCI
were observed in over one-third of patients treated, and were most common in the
first year on ART. High baseline CD4 count at ART initiation was the greatest
predictor of subsequent UCI. CONCLUSIONS: Interventions focused on the first year
on ART are needed to improve continuity of HIV care.
PMID- 26424508
TI - A fully parallel in time and space algorithm for simulating the electrical
activity of a neural tissue.
AB - BACKGROUND: The resolution of a model describing the electrical activity of
neural tissue and its propagation within this tissue is highly consuming in term
of computing time and requires strong computing power to achieve good results.
NEW METHOD: In this study, we present a method to solve a model describing the
electrical propagation in neuronal tissue, using parareal algorithm, coupling
with parallelization space using CUDA in graphical processing unit (GPU).
RESULTS: We applied the method of resolution to different dimensions of the
geometry of our model (1-D, 2-D and 3-D). The GPU results are compared with
simulations from a multi-core processor cluster, using message-passing interface
(MPI), where the spatial scale was parallelized in order to reach a comparable
calculation time than that of the presented method using GPU. A gain of a factor
100 in term of computational time between sequential results and those obtained
using the GPU has been obtained, in the case of 3-D geometry. Given the structure
of the GPU, this factor increases according to the fineness of the geometry used
in the computation. COMPARISON WITH EXISTING METHOD(S): To the best of our
knowledge, it is the first time such a method is used, even in the case of
neuroscience. CONCLUSION: Parallelization time coupled with GPU parallelization
space allows for drastically reducing computational time with a fine resolution
of the model describing the propagation of the electrical signal in a neuronal
tissue.
PMID- 26424507
TI - In vivo imaging of axonal transport in murine motor and sensory neurons.
AB - BACKGROUND: Axonal transport is essential for neuronal function and survival.
Defects in axonal transport have been identified as an early pathological feature
in several disorders of the nervous system. The visualisation and quantitative
analysis of axonal transport in vivo in rodent models of neurological disease is
therefore crucial to improve our understanding of disease pathogenesis and for
the identification of novel therapeutics. NEW METHOD: Here, we describe a method
for the in vivo imaging of axonal transport of signalling endosomes in the
sciatic nerve of live, anaesthetised mice. RESULTS: This method allows the
multiparametric, quantitative analysis of in vivo axonal transport in motor and
sensory neurons of adult mice in control conditions and during disease
progression. COMPARISON WITH EXISTING METHODS: Previous in vivo imaging of the
axonal transport of signalling endosomes has been limited to studies in nerve
explant preparations or non-invasive approaches using magnetic resonance imaging;
techniques that are hampered by major drawbacks such as tissue damage and low
temporal and spatial resolution. This new method allows live imaging of the
axonal transport of single endosomes in the sciatic nerve in situ and a more
sensitive analysis of axonal transport kinetics than previous approaches.
CONCLUSIONS: The method described in this paper allows an in-depth analysis of
the characteristics of axonal transport in both motor and sensory neurons in
vivo. It enables the detailed study of alterations in axonal transport in rodent
models of neurological diseases and can be used to identify novel pharmacological
modifiers of axonal transport.
PMID- 26424509
TI - The challenges of reshaping disease specific and care oriented community based
services towards comprehensive goals: a situation appraisal in the Western Cape
Province, South Africa.
AB - BACKGROUND: Similar to other countries in the region, South Africa is currently
reorienting a loosely structured and highly diverse community care system that
evolved around HIV and TB, into a formalized, comprehensive and integrated
primary health care outreach programme, based on community health workers (CHWs).
While the difficulties of establishing national CHW programmes are well
described, the reshaping of disease specific and care oriented community
services, based outside the formal health system, poses particular challenges.
This paper is an in-depth case study of the challenges of implementing reforms to
community based services (CBS) in one province of South Africa. METHODS: A multi
method situation appraisal of CBS in the Western Cape Province was conducted over
eight months in close collaboration with provincial stakeholders. The appraisal
mapped the roles and service delivery, human resource, financing and governance
arrangements of an extensive non-governmental organisation (NGO) contracted and
CHW based service delivery infrastructure that emerged over 15-20 years in this
province. It also gathered the perspectives of a wide range of actors - including
communities, users, NGOs, PHC providers and managers - on the current state and
future visions of CBS. RESULTS: While there was wide support for new approaches
to CBS, there are a number of challenges to achieving this. Although largely
government funded, the community based delivery platform remains marginal to the
formal public primary health care (PHC) and district health systems. CHW roles
evolved from a system of home based care and are limited in scope. There is a
high turnover of cadres, and support systems (supervision, monitoring, financing,
training), coordination between CHWs, NGOs and PHC facilities, and sub-district
capacity for planning and management of CBS are all poorly developed.
CONCLUSIONS: Reorienting community based services that have their origins in care
responses to HIV and TB presents an inter-related set of resource mobilisation,
system design and governance challenges. These include not only formalising
community based teams themselves, but also the forging of new roles,
relationships and mind-sets within the primary health care system, and creating
greater capacity for contracting and engaging a plural set of actors -
government, NGO and community - at district and sub-district level.
PMID- 26424510
TI - A comparison of intervention and conservative treatment for angulated fractures
of the distal forearm in children (AFIC): study protocol for a randomized
controlled trial.
AB - BACKGROUND: Angulated fractures of the distal forearm are very frequent lesions
in childhood. Currently, there are no standard guidelines on whether these
children should be treated conservatively with a cast; with reduction and a cast;
or with reduction, pinning and a cast under anesthesia. Minor prospective and
retrospective studies have shown that the distal physis of the forearm possesses
high remodeling capacity leading to reliable correction of malalignment. The aim
of this trial is to answer the question about whether operative and conservative
treatment show equivocal results. METHODS/DESIGN: This is a prospective,
multinational, multicenter, randomized, observer-blinded, actively controlled,
parallel group trial, with 24 months of observation. The primary objective of
this trial is to assess whether or not the long-term functional outcome in
remodeling patients is inferior to patients receiving closed reduction and K-wire
pinning. The trial should include 742 patients with acute fracture. The patients
will be included in 30 medical centers in Germany, Switzerland and Austria. All
patients 5 to 11 years of age presenting at the emergency department with an
angulated distal fracture of the forearm will be randomized online after informed
consent. The primary endpoint is the Cooney Score after 24 months. The secondary
endpoint is the grade of radiological displacement at 12/24 months. DISCUSSION:
Therapy of angulated fractures is a matter of intensive debate. Primary
manipulation and pinning under general anesthesia is recommended in order to
avoid malalignment. No major study has proven the advantage of manipulation and
pinning over immobilization alone. Should remodeling appear to be a safe
alternative, manipulation under general anesthesia, K-wire pinning and removal of
pins could be avoided, thus sparing significant costs. TRIAL REGISTRATION:
DRKS00004874 , 30 October 2013.
PMID- 26424512
TI - Medical Researchers' Ancillary Care Obligations: The Relationship-Based Approach.
AB - In this article, I provide a new account of the basis of medical researchers'
ancillary care obligations. Ancillary care in medical research, or medical care
that research participants need but that is not required for the validity or
safety of a study or to redress research injuries, is a topic that has drawn
increasing attention in research ethics over the last ten years. My view, the
relationship-based approach, improves on the main existing theory, Richardson and
Belsky's 'partial-entrustment model', by avoiding its problematic restriction on
the scope of health needs for which researchers could be obligated to provide
ancillary care. Instead, it grounds ancillary care obligations in a wide range of
morally relevant features of the researcher-participant relationship, including
the level of engagement between researchers and participants, and weighs these
factors against each other. I argue that the level of engagement, that is, the
duration and intensity of interactions, between researchers and participants
matters for ancillary care because of its connection to the meaningfulness of a
relationship, and I suggest that other morally relevant features can be grounded
in researchers' role obligations.
PMID- 26424511
TI - Psychiatric symptoms in adolescents: FKBP5 genotype--early life adversity
interaction effects.
AB - Psychiatric disorders are multi-factorial and their symptoms overlap.
Constitutional and environmental factors influence each other, and this
contributes to risk and resilience in mental ill-health. We investigated
functional genetic variation of stress responsiveness, assessed as FKBP5
genotype, in relation to early life adversity and mental health in two samples of
adolescents. One population-based sample of 909 12-year-old adolescents was
assessed using the Life Incidence of Traumatic Events scale and the Strengths and
Difficulties Questionnaire. One sample of 398 17-year-old adolescents, enriched
for poly-victimized individuals (USSS), was assessed using the Juvenile
Victimization Questionnaire and the Trauma Symptom Checklist for Children (TSCC).
The FKBP5 rs1360780 and rs3800373 polymorphisms were genotyped using a
fluorescence-based competitive allele-specific PCR. Most prominently among poly
victimized older male adolescents, the least common alleles of the polymorphisms,
in interaction with adverse life events, were associated with psychiatric
symptoms, after controlling for ethno-socio-economic factors. The interaction
effect between rs3800373 and adverse life events on the TSCC sub-scales-anxiety,
depression, anger, and dissociation-and with the rs1360780 on dissociation in the
USSS cohort remained significant after Bonferroni correction. This pattern of
association is in line with the findings of clinical and neuroimaging studies,
and implies interactive effects of FKBP5 polymorphisms and early life environment
on several psychiatric symptoms. These correlates add up to provide constructs
that are relevant to several psychiatric symptoms, and to identify early
predictors of mental ill-health.
PMID- 26424514
TI - Brain activity modifications following spinal cord stimulation for chronic
neuropathic pain: A systematic review.
AB - BACKGROUND AND OBJECTIVE: Spinal cord stimulation (SCS) is believed to exert
supraspinal effects; however, these mechanisms are still far from fully
elucidated. This systematic review aims to assess existing neurophysiological and
functional neuroimaging literature to reveal current knowledge regarding the
effects of SCS for chronic neuropathic pain on brain activity, to identify gaps
in knowledge, and to suggest directions for future research. DATABASES AND DATA
TREATMENT: Electronic databases and hand-search of reference lists were employed
to identify publications investigating brain activity associated with SCS in
patients with chronic neuropathic pain, using neurophysiological and functional
neuroimaging techniques (fMRI, PET, MEG, EEG). Studies investigating patients
with SCS for chronic neuropathic pain and studying brain activity related to SCS
were included. Demographic data (age, gender), study factors (imaging modality,
patient diagnoses, pain area, duration of SCS at recording, stimulus used) and
brain areas activated were extracted from the included studies. RESULTS: Twenty
four studies were included. Thirteen studies used neuroelectrical imaging
techniques, eight studies used haemodynamic imaging techniques, two studies
employed both neuroelectrical and haemodynamic techniques separately, and one
study investigated cerebral neurobiology. CONCLUSIONS: The limited available
evidence regarding supraspinal mechanisms of SCS does not allow us to develop any
conclusive theories. However, the studies included appear to show an inhibitory
effect of SCS on somatosensory evoked potentials, as well as identifying the
thalamus and anterior cingulate cortex as potential mediators of the pain
experience. The lack of substantial evidence in this area highlights the need for
large-scale controlled studies of this kind.
PMID- 26424513
TI - LUCID: A Quantitative Assay of ESCRT-Mediated Cargo Sorting into Multivesicular
Bodies.
AB - Endosomes are transportation nodes, mediating selective transport of soluble and
transmembrane cargos to and from the Golgi apparatus, plasma membrane and
lysosomes. As endosomes mature to become multivesicular bodies (MVBs), Endosomal
Sorting Complexes Required for Transport (ESCRTs) selectively incorporate
transmembrane cargos into vesicles that bud into the endosome lumen. Luminal
vesicles and their cargoes are targeted for destruction when MVBs fuse with
lysosomes. Common assays of endosomal luminal targeting, including fluorescence
microscopy and monitoring of proteolytic cargo maturation, possess significant
limitations. We present a quantitative assay system called LUCID (LUCiferase
reporter of Intraluminal Deposition) that monitors exposure of chimeric
luciferase-cargo reporters to cytosol. Luciferase-chimera signal increases when
sorting to the endosome lumen is disrupted, and silencing of signal from the
chimera depends upon luminal delivery of the reporter rather than proteolytic
degradation. The system presents several advantages, including rapidity,
microscale operation and a high degree of reproducibility that enables detection
of subtle phenotypic differences. Luciferase reporters provide linear signal over
an extremely broad dynamic range, allowing analysis of reporter traffic even at
anemic levels of expression. Furthermore, LUCID reports transport kinetics when
applied to inducible trafficking reporters.
PMID- 26424515
TI - The influence of sun exposure on the DNA methylation status of MMP9, miR-137,
KRT14 and KRT19 genes in human skin.
AB - BACKGROUND: Studies have shown that a variety of environmental factors and habits
are associated with epigenetic changes. In addition, various genes are also found
to respond to UV radiation. OBJECTIVES: The aim of this study was to investigate
the sun exposure influence on the DNA methylation profile on the matrix
metalloprotease-9 (MMP9), microRNA 137 (miR-137), cytokeratin 14 (KRT14) and 19
(KRT19) genes of skin cells of subjects with no history of skin diseases.
METHODS: Skin biopsies (5mm) were obtained using a punch technique on sun-exposed
(outer forearm) and sun-protected areas (inner arm) from 30 corpses from the
Brazilian Service of Death Investigation. Skin types were ranked according to
Fitzpatrick's criteria. Genomic DNA was extracted and a DNA methylation analysis
was performed using Methylation Specific PCR (MSP) or Methylation-Sensitive
Restriction Enzymes (MSRE) of sun-exposed and sun-protected skin areas. RESULTS:
No differences were found among the areas (p>0.05; McNemar), with the partially
methylated condition found to be a common event in skin for both MMP9 and miR-137
genes and the methylated condition for both KRT14 and KRT19 genes. Additional
analysis showed no differences in the methylation status when age, gender and
skin type were considered, however, the methylation status of miR-137 gene seems
to be gender-related. CONCLUSIONS: We conclude that sun exposure does not induce
changes in the DNA methylation status in MMP9, miR-137, KRT14 and KRT19 genes.
PMID- 26424517
TI - The 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary
hypertension: a practical chronicle of progress.
PMID- 26424518
TI - The 2015 guidelines for idiopathic pulmonary fibrosis: an important chapter in
the evolution of the management of patients with IPF.
PMID- 26424516
TI - From stem cells to the law courts: DNA methylation, the forensic epigenome and
the possibility of a biosocial archive.
PMID- 26424519
TI - Classification of antituberculosis drugs: a new proposal based on the most recent
evidence.
PMID- 26424520
TI - Multitasking basal cells: combining stem cell and innate immune duties.
PMID- 26424521
TI - The double-edged sword of neutrophilic inflammation in bronchiectasis.
PMID- 26424522
TI - Should COPD stand for "comorbidity-related obstructive pulmonary disease"?
PMID- 26424523
TI - Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature
review.
AB - Idiopathic pulmonary fibrosis (IPF) is associated with a fatal prognosis and
manifests in patients over 60 years old who may have comorbidities. The
prevalence and impact of comorbidities on the clinical course of IPF is
unclear.This systematic literature review examined the prevalence of
comorbidities and mortality associated with comorbidities in IPF patients.
Relevant observational studies published in English from January 1990 to January
2015 identified via MEDLINE and EMBASE were included; bibliographies of articles
were also searched.Among the 126 studies included, prevalence of pulmonary
hypertension (PH) was 3-86%, 6-91% for obstructive sleep apnoea, 3-48% for lung
cancer and 6-67% for chronic obstructive pulmonary disease (COPD). Nonrespiratory
comorbidities included ischaemic heart disease (IHD) (3-68%) and gastro
oesophageal reflux (GER) (0-94%). Mortality was highest among patients with IPF
and lung cancer. Most studies assessed relatively small samples of patients with
IPF.PH, COPD, lung cancer, GER and IHD are significant comorbidities; differences
in IPF severity, case definitions and patient characteristics limited the
comparability of findings. The identification and prompt treatment of
comorbidities may have a clinically significant impact on overall outcome that is
meaningful for patients with IPF.
PMID- 26424524
TI - Pulse oximetry oxygen saturation during the 6-min walk test: a limit for stopping
the test without resuming it.
PMID- 26424525
TI - Guidance for the regulatory status of allergen extracts in clinical trials.
PMID- 26424526
TI - "Dead space: the physiology of wasted ventilation." H. Thomas Robertson. Eur
Respir J 2015; 45: 1704-1716.
PMID- 26424528
TI - Dermoscopy and reflectance confocal microscopy in cutaneous leishmaniasis on the
face.
PMID- 26424529
TI - The effect of the phytol-rich fraction from Lacistema pubescens against
Leishmania amazonensis is mediated by mitochondrial dysfunction.
AB - Leishmaniasis is a complex disease caused by protozoan parasite Leishmania and
the treatment remains a serious problem since the available drugs exhibited high
toxicity and side effects. Plant-derived natural products are promising leads for
the development of novel chemotherapeutics. In this work the phytol-rich hexane
fraction (PRF) from the leaves of Lacistema pubescens was obtained and identified
by GC-MS analysis. When assayed for antileishmanial effects, PRF was active
against promastigote and amastigote forms of Leishmania amazonensis (IC50 values
of 44.0 and 25.8 MUg/mL respectively). Furthermore, PRF did not show significant
cytotoxicity on peritoneal macrophages being more destructive to the
intracellular parasite than to mammalian cells. In addition, possible targets of
PRF were investigated against L. amazonensis promastigotes. The results showed
that PRF exerted its antipromastigote activity by marked depolarization of the
mitochondrial membrane potential followed by the increase of ROS levels in L.
amazonensis promastigotes. During these events, no rupture of the cell membrane
integrity was observed. Our results indicated that PRF was effective and
selective against L. amazonensis, and that this effect was mainly mediated by
mitochondrial dysfunction associated to ROS production.
PMID- 26424530
TI - Real life management of community-acquired Pneumonia in adults in the Gulf region
and comparison with practice guidelines: a prospective study.
AB - BACKGROUND: Very few data exist on the management of community-acquired pneumonia
(CAP) in patients admitted to hospitals in the Gulf region. The objectives of
this study were to describe treatment patterns for CAP in 38 hospitals in five
Gulf countries (United Arab Emirates, Kuwait, Bahrain, Oman, and Qatar) and to
compare the findings to the most recent Infectious Diseases Society of America
(IDSA)/American Thoracic Society (ATS) guidelines. METHODS: This was a
prospective, observational study conducted between January 2009 and February
2011. Adult patients hospitalised (excluding intensive care units) for CAP and
subsequently discharged were included. Data were collected retrospectively at
hospital discharge, and prospectively during two follow-up visits. Data on
medical history, mortality-risk scores, diagnostic criteria, antibiotic
treatment, isolated pathogens and clinical and radiographic outcomes were
collected. Care practices were compared to the IDSA/ATS guidelines. RESULTS: A
total of 684 patients were included. The majority (82.9 %) of patients were
classified as low risk for mortality (pneumonia severity index II and III). The
majority of patients fulfilled criteria for treatment success at discharge,
although only 77.6 % presented a normalised leukocyte count. Overall, the
management of CAP in Gulf countries is in line with the IDSA/ATS guidelines. This
applied to the diagnosis of CAP, to the identification of high-risk CAP patients,
to the identification of etiologic agent responsible for CAP and to the type of
treatment despite the fact that combinations of antimicrobial agents were not
consistent with the guidelines in 10 % of patients. In all patients, information
about Gram's staining was not captured as recommended by the IDSA/ATS and in the
majority of patients (>85 %) chest radiography was not systematically performed
at the post-discharge follow-up visits. DISCUSSION: The management of CAP in the
Gulf region is globally in line with current IDSA/ATS guidelines, although rates
of pathogen characterisation and post-discharge follow-up need to be improved.
CONCLUSION: Compliance with established guidelines should be encouraged in order
to improve the management of the disease in this region.
PMID- 26424531
TI - University Students Intend to Eat Better but Lack Coping Self-Efficacy and
Knowledge of Dietary Recommendations.
AB - OBJECTIVE: To assess university students' knowledge, intentions, and coping self
efficacy related to dietary recommendations. DESIGN: The study used a cross
sectional online survey. SETTING: Large university campus. PARTICIPANTS: Students
(n = 6,638; 22% response). VARIABLES MEASURED: Self-efficacy and intentions were
measured using 11-point scales. Students' perceived dietary recommendations were
evaluated as correct or incorrect. ANALYSIS: Categorical variables were analyzed
using chi-square and continuous variables by t tests or ANOVAs. Significance was
set at P <= .05 and multiple comparisons at P <= .01. RESULTS: Respondents
believed that they need fewer vegetables and fruit and more milk or alternatives
servings/d than recommended; eg, males aged >= 19 years perceived milk or
alternatives recommendations to be 4.3 +/- 2.1 servings/d, significantly more
than the 2 servings/d recommended (P < .001). Students in health sciences or with
a food or nutrition course were significantly more likely to claim that they met
recommendations (eg, 56% with vs 47% without a food or nutrition course for
vegetables and fruit; P < .001); however, they were no more likely to identify
them correctly. Males aged < 19 years had higher coping self-efficacy than
females aged < 19 years to consume vegetables (68.3 +/- 24.2 vs 64.0 +/- 24.7; P
< .01) and avoid high-calorie foods and beverages (HCFB) (56.2 +/- 27.2 vs 49.0
+/- 25.2; P < .01) when under stress; however, they had significantly lower
intentions to consume vegetables (72.1 +/- 24.5 vs 80.9 +/- 20.3; P < .01) and
avoid HCFB (60.5 +/- 30.3 vs 77.7 +/- 22.8; P < .01). CONCLUSIONS AND
IMPLICATIONS: Students do not have adequate knowledge of age- and sex-specific
food guide recommendations. Simpler food guide recommendations or age- and sex
targeted campaigns may enhance knowledge. Students intend to consume more
vegetables and less HCFB; however, they have low coping self-efficacy, all of
which could be targeted in nutrition interventions.
PMID- 26424532
TI - Bonding and Bridging Social and Cultural Capitals: Perceived Factors Associated
With Family Eating Practices Among Hmong, Latino, and White Mothers and Fathers.
AB - OBJECTIVE: To examine perceived social and cultural capitals associated with
family eating practices among Hmong, Latino, and white mothers and fathers.
METHODS: Six focus groups composed of 52 Hmong, Latino, and white mothers and
fathers of young children were conducted to examine parental perceptions of
social and cultural capitals associated with eating practices. RESULTS: Whereas
Hmong participants unanimously emphasized the healthfulness of their traditional
food, Latino groups had divergent views on their traditional foods'
healthfulness. Hmong parents highly valued their traditional foods whereas white
and Latino mothers were more accepting of new foods from other cultures.
Participants noted divergent views on gender roles in family eating practices and
food culture preservation efforts. CONCLUSIONS AND IMPLICATIONS: Identifying and
promoting bonding and bridging of cultural assets for healthy dietary practices
among different cultural groups may be important for developing successful
nutrition education programs across ethnicities in the community.
PMID- 26424533
TI - Unit cell structure of water-filled monoolein in inverted hexagonal mesophase in
the presence of incorporated tricaprylin and entrapped lysozyme.
AB - Molecular dynamics (MD) was employed by means of a specific simulation protocol
to investigate the equilibrium structure at 25 degrees C of the hexagonal
inverted (HII) mesophase composed from water, 1-monoolein (GMO), and tricaprylin,
with or without entrapped lysozyme. Based on robust and fast MD simulations, the
study provides a comprehensive analysis and visualization of the local structure
of HII mesophase containing admixtures. The most important physical insight is
the possibility to observe the strong self-recovery capacity of the GMO layer,
which allows the HII mesophase tubes to reorganize and host lysozyme molecules
with a size bigger than the diameter of the water channel. This is a direct
message to the experimenters that the HII mesophase has the potential to host
molecules larger than the diameter of the water channel. Collective character of
the interlipid interactions is outlined, which is not affected by the presence of
the cargo and may be the reason for the efficient GMO reorganization. Another
important result is the possible explanation of the role of triacylglycerols on
the low-temperature stabilization of the HII mesophase. The analysis shows that
despite the low amount of tricaprylin, its molecules prevent the extreme
inclination of the lipid tails and thus optimize the alignment capacity of the
lipid tails layer. The study also reveals that the packing frustration does not
depend on the temperature and the presence of admixtures. Hence, it might be
numerically defined as a universal invariant parameter of a stable HII mesophase
composed of a certain lipid.
PMID- 26424534
TI - [Patient Blood Management: where to start?].
PMID- 26424536
TI - Regulatory RNAs discovered in unexpected places.
AB - Recent studies have discovered both small and long noncoding RNAs (ncRNAs)
encoded in unexpected places. These ncRNA genes were surprises at the time of
their discovery, but many quickly became well-accepted families of functional
regulatory RNA species. Even after years of extensive gene annotation studies
using high-throughput sequencing technologies, new types of ncRNA genes continue
to be discovered in unexpected places. We highlight ncRNAs that have atypical
structures and that are encoded in what are generally considered 'junk'
sequences, such as spacers and introns. We also discuss current bottlenecks in
the approaches for identifying novel ncRNAs and the possibility that many remain
to be discovered.
PMID- 26424538
TI - Night-time assaults in Newcastle 6-7 years after trading hour restrictions.
PMID- 26424537
TI - Narrow pH Range of Surface Water Bodies Receiving Pesticide Input in Europe.
AB - Fate and toxicity of the active ingredients (AI's) of plant protection products
in surface waters is often influenced by pH. Although a general range of pH
values is reported in literature, an evaluation targeting aquatic ecosystems with
documented AI inputs is lacking at the larger scale. Results show 95% of European
surface waters (n = 3075) with a documented history of AI exposure fall within a
rather narrow pH range, between 7.0 and 8.5. Spatial and temporal variability in
the data may at least be partly explained by the calcareous characteristics of
parental rock material, the affiliation of the sampling site to a freshwater
ecoregion, and the photosynthetic activity of macrophytes (i.e., higher pH values
with photosynthesis). Nonetheless, the documented pH range fits well with the
standard pH of most ecotoxicological test guidelines, confirming the fate and
ecotoxicity of AIs are usually adequately addressed.
PMID- 26424539
TI - Non-motor symptoms and quality of life in patients with Parkinson's disease in
Northeastern Mexico.
AB - Parkinson's disease (PD) is a multisystem disorder, and besides the classical
motor symptoms it is now known that patients also suffer from a variety of non
motor symptoms that adversely affect quality of life (QOL). Since data on
Hispanic populations on this issue are scarce, our aim was to study the
association of non-motor symptoms and QOL in patients with PD. This study is a
cross-sectional observational study involving patients with PD using the
following instruments: Quality of Life Questionnaire (PDQ-8), Unified Parkinson's
Disease Rating Scale part III (UPDRS part III), and Non-Motor Symptom Scale
(NMSS). We included 52 patients, with a median age of 64 years. Sleep/fatigue and
mood/cognitive domains were the most common non-motor symptoms. Only
sleep/fatigue, mood/cognition and gastrointestinal domains were associated with
worse PDQ-8 scores. After adjusting for confounding variables, NMSS scores were
significantly associated with a high PDQ-8 score. Higher NMSS scores were
associated with and predicted higher PDQ-8 scores. The focus of management in PD
should shift to a comprehensive strategy that incorporates care of non-motor
symptoms and improves QOL.
PMID- 26424535
TI - Choices for Induction of Pluripotency: Recent Developments in Human Induced
Pluripotent Stem Cell Reprogramming Strategies.
AB - The ability to generate human induced pluripotent stem cells (iPSCs) from somatic
cells provides tremendous promises for regenerative medicine and its use has
widely increased over recent years. However, reprogramming efficiencies remain
low and chromosomal instability and tumorigenic potential are concerns in the use
of iPSCs, especially in clinical settings. Therefore, reprogramming methods have
been under development to generate safer iPSCs with higher efficiency and better
quality. Developments have mainly focused on the somatic cell source, the
cocktail of reprogramming factors, the delivery method used to introduce
reprogramming factors and culture conditions to maintain the generated iPSCs.
This review discusses the developments on these topics and briefly discusses pros
and cons of iPSCs in comparison with human embryonic stem cells generated from
somatic cell nuclear transfer.
PMID- 26424540
TI - Hereditary multiple exostoses: an unusual cause of spinal cord compression.
PMID- 26424541
TI - Wireless non-invasive continuous respiratory monitoring with FMCW radar: a
clinical validation study.
AB - Altered respiratory rate is one of the first symptoms of medical conditions that
require timely intervention, e.g., sepsis or opioid-induced respiratory
depression. To facilitate continuous respiratory rate monitoring on general
hospital wards a contactless, non-invasive, prototype monitor was developed using
frequency modulated continuous wave radar. We aimed to study whether radar can
reliably measure respiratory rate in postoperative patients. In a diagnostic
cross-sectional study patients were monitored with the radar and the reference
monitor (pneumotachograph during mechanical ventilation and capnography during
spontaneous breathing). Eight patients were included; yielding 796 min of
observation time during mechanical ventilation and 521 min during spontaneous
breathing. After elimination of movement artifacts the bias and 95 % limits of
agreement for mechanical ventilation and spontaneous breathing were -0.12 (-1.76
to 1.51) and -0.59 (-5.82 to 4.63) breaths per minute respectively. The radar was
able to accurately measure respiratory rate in mechanically ventilated patients,
but the accuracy decreased during spontaneous breathing.
PMID- 26424543
TI - The end of AIDS?
PMID- 26424542
TI - Estimation of mortality among HIV-infected people on antiretroviral treatment in
East Africa: a sampling based approach in an observational, multisite, cohort
study.
AB - BACKGROUND: Mortality in HIV-infected people after initiation of antiretroviral
treatment (ART) in resource-limited settings is an important measure of the
effectiveness and comparative effectiveness of the global public health response.
Substantial loss to follow-up precludes accurate accounting of deaths and limits
our understanding of effectiveness. We aimed to provide a better understanding of
mortality at scale and, by extension, the effectiveness and comparative
effectiveness of public health ART treatment in east Africa. METHODS: In 14
clinics in five settings in Kenya, Uganda, and Tanzania, we intensively traced a
sample of patients randomly selected using a random number generator, who were
infected with HIV and on ART and who were lost to follow-up (>90 days late for
last scheduled visit). We incorporated the vital status outcomes for these
patients into analyses of the entire clinic population through probability
weighted survival analyses. FINDINGS: We followed 34 277 adults on ART from
Mbarara and Kampala in Uganda, Eldoret, and Kisumu in Kenya, and Morogoro in
Tanzania. The median age was 35 years (IQR 30-42), 11 628 (34%) were men, and
median CD4 count count before therapy was 154 cells per MUL (IQR 70-234). 5780
patients (17%) were lost to follow-up, 991 (17%) were selected for tracing
between June 10, 2011, and Aug 27, 2012, and vital status was ascertained for 860
(87%). With incorporation of outcomes from the patients lost to follow-up,
estimated 3 year mortality increased from 3.9% (95% CI 3.6-4.2) to 12.5% (11.8
13.3). The sample-corrected, unadjusted 3 year mortality across settings was
lowest in Mbarara (7.2%) and highest in Morogoro (23.6%). After adjustment for
age, sex, CD4 count before therapy, and WHO stage, the sample-corrected hazard
ratio comparing the settings with highest and lowest mortalities was 2.2 (95% CI
1.5-3.4) and the risk difference for death at 3 years was 11% (95% CI 5.0-17.7).
INTERPRETATION: A sampling-based approach is widely feasible and important to an
understanding of mortality after initiation of ART. After adjustment for measured
biological drivers, mortality differs substantially across settings despite
delivery of a similar clinical package of treatment. Implementation research to
understand the systems, community, and patients' behaviours driving these
differences is urgently needed. FUNDING: The US National Institutes of Health and
President's Emergency Fund for AIDS Relief.
PMID- 26424544
TI - Trying to cure HIV with immunotherapy: not so simple.
PMID- 26424545
TI - End of AIDS on the horizon, but innovation needed to end HIV.
PMID- 26424546
TI - CD4/CD8 ratio: an emerging biomarker for HIV.
PMID- 26424547
TI - Where have all the patients gone?
PMID- 26424548
TI - How can we end paediatric AIDS?
PMID- 26424549
TI - Effect of therapeutic intensification followed by HIV DNA prime and rAd5 boost
vaccination on HIV-specific immunity and HIV reservoir (EraMune 02): a
multicentre randomised clinical trial.
AB - BACKGROUND: Achievement of a cure for HIV infection might need reactivation of
latent virus and improvement of HIV-specific immunity. As an initial step, in
this trial we assessed the effect of antiretroviral therapy intensification and
immune modulation with a DNA prime and recombinant adenovirus 5 (rAd5) boost
vaccine. METHODS: In this multicentre, randomised, open-label, non-comparative,
phase 2 clinical trial, we enrolled eligible adults 18-70 years of age with
chronic HIV-1 infection on suppressive antiretroviral therapy with current CD4
count of at least 350 cells per MUL and HIV DNA between 10 and 1000 copies per
10(6) peripheral blood mononuclear cells. After an 8 week lead-in of
antiretroviral intensification therapy (standard dose raltegravir and dose
adjusted maraviroc based on baseline antiretroviral therapy), patients were
randomly assigned (1:1) to receive antiretroviral therapy intensification alone
or intensification plus injections of HIV DNA prime vaccine (4 mg VRC-HIVDNA016
00-VP) at weeks 8, 12, and 16, followed by HIV rAd5 boost vaccine (10(10)
particle units of VRC-HIVADV014-00-VP) at week 32. Randomisation was computer
generated in permuted blocks of six and was stratified by study site. The primary
endpoint was a 0.5 log10 or greater decrease in HIV DNA in peripheral blood
mononuclear cells at week 56. This study is registered with ClinicalTrials.gov,
number NCT00976404. FINDINGS: Between Nov 29, 2010, and Oct 28, 2011, we enrolled
28 eligible patients from three academic HIV clinics in the USA. After the 8 week
lead-in of antiretroviral intensification therapy, 14 patients were randomly
assigned to continue antiretroviral therapy intensification alone and 14 to
intensification plus vaccine. Enrolled participants had median CD4 count of 636
cells per MUL, median HIV DNA 170 copies per 10(6) peripheral blood mononuclear
cells, and duration of antiretroviral therapy of 13 years. The median amount of
HIV DNA did not change significantly between baseline and week 56 in the
antiretroviral therapy intensification plus vaccine group. One participant in the
antiretroviral therapy intensification alone group reached the primary endpoint,
with 0.55 log10 decrease in HIV DNA in peripheral blood mononuclear cells. Both
treatments were well tolerated. No severe or systemic reactions to vaccination
occurred, and five serious adverse events were recorded during the study, most of
which resolved spontaneously or were judged unrelated to study treatments.
INTERPRETATION: Antiretroviral therapy intensification followed by DNA prime and
rAd5 boost vaccine did not significantly increase HIV expression or reduce the
latent HIV reservoir. A multifaceted approach that includes stronger activators
of HIV expression and novel immune modulators will probably be needed to reduce
the latent HIV reservoir and allow for long-term control in patients off
antiretroviral therapy. FUNDING: Objectif Recherche Vaccin SIDA (ORVACS).
PMID- 26424551
TI - Metabolic Engineering of Wheat Provitamin A by Simultaneously Overexpressing CrtB
and Silencing Carotenoid Hydroxylase (TaHYD).
AB - Increasing the provitamin A content in staple crops via carotenoid metabolic
engineering is one way to address vitamin A deficiency. In this work a
combination of methods was applied to specifically increase beta-carotene content
in wheat by metabolic engineering. Endosperm-specific silencing of the carotenoid
hydroxylase gene (TaHYD) increased beta-carotene content 10.5-fold to 1.76 MUg g(
1) in wheat endosperm. Overexpression of CrtB introduced an additional flux into
wheat, accompanied by a beta-carotene increase of 14.6-fold to 2.45 MUg g(-1).
When the "push strategy" (overexpressing CrtB) and "block strategy" (silencing
TaHYD) were combined in wheat metabolic engineering, significant levels of beta
carotene accumulation were obtained, corresponding to an increase of up to 31
fold to 5.06 MUg g(-1). This is the first example of successful metabolic
engineering to specifically improve beta-carotene content in wheat endosperm
through a combination of methods and demonstrates the potential of genetic
engineering for specific nutritional enhancement of wheat.
PMID- 26424552
TI - Down-regulation of PAR1 activity with a pHLIP-based allosteric antagonist induces
cancer cell death.
AB - Even though abnormal expression of G protein-coupled receptors (GPCRs) and of
their ligands is observed in many cancer cells of various origins, only a few
anti-cancer compounds directly act on their signalling. One promising approach to
modulate their activity consists of targeting the receptor cytoplasmic surfaces
interacting with the associated G-proteins using peptides mimicking the
intracellular loops of the receptor. Thus, to be fully effective, the peptide
mimics must be selectively targeted to the tumour while sparing healthy tissues,
translocated across the cell membrane and stay anchored to the cytoplasmic
leaflet of the plasma membrane. In the present study, we introduce a novel way to
selectively target and inhibit the activity of a GPCR in cancer cells under
acidic conditions, such as those found in solid tumours. We find that the
conjugation of a peptide fragment derived from the third intracellular loop (i3)
of the protease-activated receptor 1 (PAR1) to a peptide that can selectively
target tumours solely based on their acidity [pH(Low) Insertion Peptide (pHLIP)],
produces a construct capable of effectively down-regulating PAR1 activity in a
concentration- and pH-dependent manner and of inducing a potent cytotoxic effect
in a panel of cancer cells that is proportional to the relative level of receptor
expression at the cell surface. This strategy not only allows for a more
selective targeting and specific intracellular delivery than current approaches,
but also offers new possibilities for developing novel anti-cancer drugs
targeting GPCRs.
PMID- 26424553
TI - Salvaging lowermost deployment of an acurate device during transcatheter aortic
valve replacement with balloon and lasso pull techniques.
AB - Transcatheter aortic valve replacement (TAVR), also known as transcatheter aortic
valve implantation (TAVI), is being used with increasing frequency in patients
with severe aortic stenosis at high or prohibitive surgical risk. A number of
devices are becoming available for TAVR, and competence in using them is
mandatory to maximize the safety and efficacy of TAVR, while individualizing
device selection in keeping with patient features. The ACURATE TF is a novel
promising device for transfemoral TAVR. However, its peculiar features may
require additional maneuvers in case of complications. We hereby report the case
of a patient undergoing transfemoral TAVR with the ACURATE TF device, in whom
lowermost deployment was complicated by massive aortic regurgitation. With two
separate remedial actions, the balloon pull and lasso techniques, we were able to
pull back the device and significantly reduce post-TAVR aortic regurgitation.
Awareness of this complication and the possible use of these two techniques may
increase the safety and efficacy of TAVR with this and other new devices. (c)
2015 Wiley Periodicals, Inc.
PMID- 26424554
TI - Gastric-type extremely well-differentiated adenocarcinoma arising in the blind
pouch of a bypassed stomach, presenting as colonic pseudo-obstruction.
AB - Gastric carcinoma after gastric bypass is rare. Extremely well-differentiated
adenocarcinoma (EWDA) of the stomach is a rare variant that has been mostly
reported in Japan. We present a case of a 68-year-old man with EWDA arising in
the bypassed stomach that presented as a colonic pseudo-obstruction (CPO).
Several imaging, endoscopic and pathologic studies performed in the course of 2
months were non-diagnostic. An iatrogenic duodenal perforation during a
diagnostic procedure led to an emergent exploratory laparotomy in which the
dilated colonic segment was resected. Pathologic examination showed metastatic
EWDA in the colonic wall. Post-operative complications led to the patient's
demise. At autopsy the primary tumor was identified in the blind pouch of the
bypassed stomach. A literature review on gastric EWDA and carcinomas arising in
bypassed stomachs is discussed. EWDA of the stomach is rare, difficult to
diagnose, and shows an aggressive clinical course discordant with its near-benign
histology. Gastric cancer arising in a bypassed stomach is uncommon; when it
occurs it is usually diagnosed at advanced stage. Surveillance of the blind pouch
is not currently recommended. Malignant infiltration of the colonic wall should
be included in the differential diagnosis of CPO of unclear etiology.
PMID- 26424550
TI - CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV
who achieve viral load suppression with antiretroviral therapy: an observational
cohort study.
AB - BACKGROUND: In patients with HIV, immune reconstitution after antiretroviral
therapy (ART) is often incomplete. We assessed the probability of patients
reaching a CD4/CD8 ratio of 1 or more after the start of ART and its association
with the onset of non-AIDS-defining events and death. METHODS: We did an analysis
of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy.
We included participants in the cohort who started ART, reached an undetectable
viral load (<=80 copies per mL), and had a CD4/CD8 ratio of less than 0.8 at the
time of an undetectable viral load. We defined ratio normalisation in patients as
two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the
cumulative probability of ratio normalisation. We then used Poisson regression
models to identify factors independently associated with normalisation and with
progression to non-AIDS-defining events or death. FINDINGS: We included 3236
participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of
ART, median CD4/CD8 ratio in our population was 0.39 (IQR 0.26-0.55). 458 (14%)
patients reached a CD4/CD8 ratio of 1 or more; the estimated probability of
normalisation was 4.4% (95% CI 3.7-5.2) by 1 year from baseline, 11.5% (10.2
13.0) by 2 years, and 29.4% (26.7-32.4) by 5 years. Factors associated with
normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at
baseline, and negative cytomegalovirus serological findings. The incidence rate
of non-AIDS-defining events for patients with a CD4/CD8 ratio of less than 0.30
(4.2 per 100 patient-years, 95% CI 3.4-5.3) was double that for those with a
ratio of 0.30-0.45 (2.3, 2.1-2.5) or more than 0.45 (2.2, 1.7-2.9). A ratio of
less than 0.30 was independently associated with an increased risk of non-AIDS
defining events or death compared with one of more than 0.45. INTERPRETATION: Few
patients had normalised CD4/CD8 ratios, even though they had viral suppression.
Low ratios were associated with increased risk of serious events and deaths. The
CD4/CD8 ratio could be used by clinicians to identity patients at risk of non
AIDS-related events. FUNDING: AbbVie, Bristol-Myers Squibb, Gilead, Janssen,
Merck Sharp & Dohme, ViiV Italy.
PMID- 26424556
TI - Erratum to: Long-term liposteroid therapy for idiopathic pulmonary hemosiderosis.
PMID- 26424555
TI - Relationship between histology, development and tumorigenesis of mammary gland in
female rat.
AB - The mammary gland is a dynamic organ that undergoes structural and functional
changes associated with growth, reproduction, and post-menopausal regression. The
postnatal transformations of the epithelium and stromal cells of the mammary
gland may contribute to its susceptibility to carcinogenesis. The increased
cancer incidence in mammary glands of humans and similarly of rodents in
association with their development is believed to be partly explained by
proliferative activity together with lesser degree of differentiation, but it is
not completely understood how the virgin gland retains its higher susceptibility
to carcinogenesis. During its developmental cycle, the mammary gland displays
many of the properties associated with breast cancer. An early first full-term
pregnancy may have a protective effect. Rodent models are useful for
investigating potential breast carcinogens. The purpose of this review is to help
recognizing histological appearance of the epithelium and the stroma of the
normal mammary gland in rats, and throughout its development in relation to
tumorigenic potential.
PMID- 26424557
TI - Kaiso represses the expression of glucocorticoid receptor via a methylation
dependent mechanism and attenuates the anti-apoptotic activity of glucocorticoids
in breast cancer cells.
AB - Kaiso is a Pox Virus and Zinc Finger (POZ-ZF) transcription factor with bi-modal
DNA-binding specificity. Here, we demonstrated that Kaiso expression is inversely
correlated with glucocorticoid receptor (GR) expression in breast carcinomas.
Knockdown of Kaiso increased GR expression, while overexpression of Kaiso
inhibited GR expression in breast cancer cells. Furthermore, Kaiso repressed GR
proximal promoter-reporter activity in a dose-dependent manner. Remarkably, ChIP
experiments demonstrated that endogenous Kaiso was associated with the GR
promoter sequence in a methylation-dependent manner. Since glucocorticoids
inhibit chemotherapyinduced apoptosis and have been widely used as a co-treatment
of patients with breast cancer, we assessed the role of Kasio in GR-mediated anti
apoptotic effects. We found that overexpression of Kaiso attenuated the anti
apoptotic effects of glucocorticoids in breast cancer cells. Our findings suggest
that GR is a putative target gene of Kaiso and suggest Kaiso to be a potential
therapeutic target in GC-combination chemotherapy in breast cancer. [BMB Reports
2016; 49(3): 167-172].
PMID- 26424559
TI - Implications of NQO1 in cancer therapy.
AB - NAD(P)H: quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is
a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates.
The NQO1- mediated two-electron reduction of quinones can be either
chemoprotection/detoxification or a chemotherapeutic response, depending on the
target quinones. When toxic quinones are reduced by NQO1, they are conjugated
with glutathione or glucuronic acid and excreted from the cells. Based on this
protective effect of NQO1, the use of dietary compounds to induce the expression
of NQO1 has emerged as a promising strategy for cancer prevention. On the other
hand, NQO1-mediated two-electron reduction converts certain quinone compounds
(such as mitomycin C, E09, RH1 and ?-lapachone) to cytotoxic agents, leading to
cell death. It has been known that NQO1 is expressed at high levels in numerous
human cancers, including breast, colon, cervix, lung, and pancreas, as compared
with normal tissues. This implies that tumors can be preferentially damaged
relative to normal tissue by cytotoxic quinone drugs. Importantly, NQO1 has been
shown to stabilize many proteins, including p53 and p33ING1b, by inhibiting their
proteasomal degradation. This review will summarize the biological roles of NQO1
in cancer, with emphasis on recent findings and the potential of NQO1 as a
therapeutic target for the cancer therapy.
PMID- 26424558
TI - Stanniocalcin 2 enhances mesenchymal stem cell survival by suppressing oxidative
stress.
AB - To overcome the disadvantages of stem cell-based cell therapy like low cell
survival at the disease site, we used stanniocalcin 2 (STC2), a family of
secreted glycoprotein hormones that function to inhibit apoptosis and oxidative
damage and to induce proliferation. STC2 gene was transfected into two kinds of
stem cells to prolong cell survival and protect the cells from the damage by
oxidative stress. The stem cells expressing STC2 exhibited increased cell
viability and improved cell survival as well as elevated expression of the
pluripotency and self-renewal markers (Oct4 and Nanog) under sub-lethal oxidative
conditions. Up-regulation of CDK2 and CDK4 and down-regulation of cell cycle
inhibitors p16 and p21 were observed after the delivery of STC2. Furthermore,
STC2 transduction activated pAKT and pERK 1/2 signal pathways. Taken together,
the STC2 can be used to enhance cell survival and maintain long-term stemness in
therapeutic use of stem cells.
PMID- 26424561
TI - Eighth International Symposium on Intensive Care and Emergency Medicine for Latin
America.
PMID- 26424560
TI - MYC and BCL-2 adjusted-International Prognostic Index (A-IPI) is a better
predictor of outcome than the standard IPI for patients with diffuse large B-cell
lymphoma treated with R-CHOP.
AB - The International Prognostic Index (IPI) has been the basis for determining
prognosis in patients with diffuse large B-cell lymphoma (DLBCL) for the past 20
years. The utility of the IPI must be reassessed in the era of
immunochemotherapy. Seven risk factors at diagnosis were identified, and a
maximum of 7 points were assigned to each patient. Four risk groups were created:
low (0-1), low-intermediate (2-3), high-intermediate (4), and high (5-7). Using
MYC and BCL-2 clinical data from the Drum Tower Hospital collected during the
rituximab era, we performed a retrospective analysis of patients with DLBCL
treated with R-CHOP and built an biological markers adjusted IPI with the goal of
improving risk stratification.Clinical features from 60 adults with de novo DLBCL
diagnosed from 2008-2013 were assessed for their prognostic significance. The IPI
remains predictive, but it cannot identify the high-risk subgroup. Compared with
the IPI, the MYC and BCL-2 adjusted-IPI (A-IPI) better discriminated patients in
the high-risk subgroup (4-year overall survival [OS]: 33.3%) than did the IPI (4
year OS: 48.0%). In the era of R-CHOP treatment, MYC and BCL-2 adjusted-IPI is
more powerful than the IPI for helping guide treatment planning and
interpretation of clinical trials.
PMID- 26424562
TI - Potentially fatal arrhythmias in two cases of adult Kawasaki disease.
AB - Fatal arrhythmias in asymptomatic Kawasaki disease patients with normal left
ventricular function have rarely been reported. In this study, we report the
cases of two adult patients with largely unpredictable sudden cardiac arrest,
despite almost-normal left ventricular function even after the diagnosis of
presumed Kawasaki disease, as well as consider the mechanisms involved with
reference to the literature.
PMID- 26424563
TI - Androgen deprivation therapy for prostate cancer: friend or foe to the
cardiovascular system?
PMID- 26424565
TI - Asthma: Undoing millions of years of coevolution in early life?
PMID- 26424564
TI - Hippocampal volume and cingulum bundle fractional anisotropy are independently
associated with verbal memory in older adults.
AB - The objective of this study was to investigate the relationship of medial
temporal lobe and posterior cingulate cortex (PCC) volumetrics as well as
fractional anisotropy of the cingulum angular bundle (CAB) and the cingulum
cingulate gyrus (CCG) bundle to performance on measures of verbal memory in non
demented older adults. The participants were 100 non-demented adults over the age
of 70 years from the Einstein Aging Study. Volumetric data were estimated from T1
weighted images. The entire cingulum was reconstructed using diffusion tensor MRI
and probabilistic tractography. Association between verbal episodic memory and
MRI measures including volume of hippocampus (HIP), entorhinal cortex (ERC), PCC
and fractional anisotropy of CAB and CCG bundle were modeled using linear
regression. Relationships between atrophy of these structures and regional
cingulum fractional anisotropy were also explored. Decreased HIP volume on the
left and decreased fractional anisotropy of left CAB were associated with lower
memory performance. Volume changes in ERC, PCC and CCG disruption were not
associated with memory performance. In regression models, left HIP volume and
left CAB-FA were each independently associated with episodic memory. The results
suggest that microstructural changes in the left CAB and decreased left HIP
volume independently influence episodic memory performance in older adults
without dementia. The importance of these findings in age and illness-related
memory decline require additional exploration.
PMID- 26424566
TI - Endogenous retroviruses in ALS: A reawakening?
PMID- 26424567
TI - Early infancy microbial and metabolic alterations affect risk of childhood
asthma.
AB - Asthma is the most prevalent pediatric chronic disease and affects more than 300
million people worldwide. Recent evidence in mice has identified a "critical
window" early in life where gut microbial changes (dysbiosis) are most
influential in experimental asthma. However, current research has yet to
establish whether these changes precede or are involved in human asthma. We
compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy
Infant Longitudinal Development (CHILD) Study, and show that infants at risk of
asthma exhibited transient gut microbial dysbiosis during the first 100 days of
life. The relative abundance of the bacterial genera Lachnospira, Veillonella,
Faecalibacterium, and Rothia was significantly decreased in children at risk of
asthma. This reduction in bacterial taxa was accompanied by reduced levels of
fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ
free mice with these four bacterial taxa ameliorated airway inflammation in their
adult progeny, demonstrating a causal role of these bacterial taxa in averting
asthma development. These results enhance the potential for future microbe-based
diagnostics and therapies, potentially in the form of probiotics, to prevent the
development of asthma and other related allergic diseases in children.
PMID- 26424568
TI - Human endogenous retrovirus-K contributes to motor neuron disease.
AB - The role of human endogenous retroviruses (HERVs) in disease pathogenesis is
unclear. We show that HERV-K is activated in a subpopulation of patients with
sporadic amyotrophic lateral sclerosis (ALS) and that its envelope (env) protein
may contribute to neurodegeneration. The virus was expressed in cortical and
spinal neurons of ALS patients, but not in neurons from control healthy
individuals. Expression of HERV-K or its env protein in human neurons caused
retraction and beading of neurites. Transgenic animals expressing the env gene
developed progressive motor dysfunction accompanied by selective loss of volume
of the motor cortex, decreased synaptic activity in pyramidal neurons, dendritic
spine abnormalities, nucleolar dysfunction, and DNA damage. Injury to anterior
horn cells in the spinal cord was manifested by muscle atrophy and pathological
changes consistent with nerve fiber denervation and reinnervation. Expression of
HERV-K was regulated by TAR (trans-activation responsive) DNA binding protein 43,
which binds to the long terminal repeat region of the virus. Thus, HERV-K
expression within neurons of patients with ALS may contribute to
neurodegeneration and disease pathogenesis.
PMID- 26424569
TI - Human IFNAR2 deficiency: Lessons for antiviral immunity.
AB - Type I interferon (IFN-alpha/beta) is a fundamental antiviral defense mechanism.
Mouse models have been pivotal to understanding the role of IFN-alpha/beta in
immunity, although validation of these findings in humans has been limited. We
investigated a previously healthy child with fatal encephalitis after inoculation
of the live attenuated measles, mumps, and rubella (MMR) vaccine. By targeted
resequencing, we identified a homozygous mutation in the high-affinity IFN
alpha/beta receptor (IFNAR2) in the proband, as well as a newborn sibling, that
rendered cells unresponsive to IFN-alpha/beta. Reconstitution of the proband's
cells with wild-type IFNAR2 restored IFN-alpha/beta responsiveness and control of
IFN-attenuated viruses. Despite the severe outcome of systemic live vaccine
challenge, the proband had previously shown no evidence of heightened
susceptibility to respiratory viral pathogens. The phenotype of IFNAR2
deficiency, together with similar findings in STAT2-deficient patients, supports
an essential but narrow role for IFN-alpha/beta in human antiviral immunity.
PMID- 26424570
TI - DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in
nonhuman primates.
AB - DEL-1 (developmental endothelial locus-1) is an endothelial cell-secreted protein
that regulates LFA-1 (lymphocyte function-associated antigen-1) integrin
dependent leukocyte recruitment and inflammation in various tissues. We
identified a novel regulatory mechanism of DEL-1 in osteoclast biology.
Specifically, we showed that DEL-1 is expressed by human and mouse osteoclasts
and regulates their differentiation and resorptive function. Mechanistically, DEL
1 inhibited the expression of NFATc1, a master regulator of osteoclastogenesis,
in a Mac-1 integrin-dependent manner. In vivo mechanistic analysis has
dissociated the anti-inflammatory from the anti-bone-resorptive action of DEL-1
and identified structural components thereof mediating these distinct functions.
Locally administered human DEL-1 blocked inflammatory periodontal bone loss in
nonhuman primates-a relevant model of human periodontitis. The ability of DEL-1
to regulate both upstream (inflammatory cell recruitment) and downstream
(osteoclastogenesis) events that lead to inflammatory bone loss paves the way to
a new class of endogenous therapeutics for treating periodontitis and perhaps
other inflammatory disorders.
PMID- 26424573
TI - The epigenetic regulator UHRF1 promotes ubiquitination-mediated degradation of
the tumor-suppressor protein promyelocytic leukemia protein.
PMID- 26424572
TI - Lessons from Ebola: Improving infectious disease surveillance to inform outbreak
management.
AB - The current Ebola virus disease outbreak in West Africa has revealed serious
shortcomings in national and international capacity to detect, monitor, and
respond to infectious disease outbreaks as they occur. Recent advances in
diagnostics, risk mapping, mathematical modeling, pathogen genome sequencing,
phylogenetics, and phylogeography have the potential to improve substantially the
quantity and quality of information available to guide the public health response
to outbreaks of all kinds.
PMID- 26424571
TI - Efficient modification of CCR5 in primary human hematopoietic cells using a
megaTAL nuclease and AAV donor template.
AB - Genetic mutations or engineered nucleases that disrupt the HIV co-receptor CCR5
block HIV infection of CD4(+) T cells. These findings have motivated the
engineering of CCR5-specific nucleases for application as HIV therapies. The
efficacy of this approach relies on efficient biallelic disruption of CCR5, and
the ability to efficiently target sequences that confer HIV resistance to the
CCR5 locus has the potential to further improve clinical outcomes. We used RNA
based nuclease expression paired with adeno-associated virus (AAV)-mediated
delivery of a CCR5-targeting donor template to achieve highly efficient targeted
recombination in primary human T cells. This method consistently achieved 8 to
60% rates of homology-directed recombination into the CCR5 locus in T cells, with
over 80% of cells modified with an MND-GFP expression cassette exhibiting
biallelic modification. MND-GFP-modified T cells maintained a diverse repertoire
and engrafted in immune-deficient mice as efficiently as unmodified cells. Using
this method, we integrated sequences coding chimeric antigen receptors (CARs)
into the CCR5 locus, and the resulting targeted CAR T cells exhibited antitumor
or anti-HIV activity. Alternatively, we introduced the C46 HIV fusion inhibitor,
generating T cell populations with high rates of biallelic CCR5 disruption paired
with potential protection from HIV with CXCR4 co-receptor tropism. Finally, this
protocol was applied to adult human mobilized CD34(+) cells, resulting in 15 to
20% homologous gene targeting. Our results demonstrate that high-efficiency
targeted integration is feasible in primary human hematopoietic cells and
highlight the potential of gene editing to engineer T cell products with myriad
functional properties.
PMID- 26424574
TI - Anterior Cruciate Ligament Injury Prevention and Rehabilitation: Let's Get It
Right.
AB - Anterior cruciate ligament (ACL) injuries are among the most common and
functionally disabling conditions in orthopaedics and sports medicine. As
professionals, we need to do a better job of screening individuals to determine
who is at greatest risk of sustaining an ACL injury, as well as implementing
injury prevention programs. We also need to do a better job with programs that
return individuals to their preinjury activity levels, including implementing
thorough functional testing to determine if a patient is ready to return to
sports or strenuous activities post-ACLR.
PMID- 26424575
TI - Chondrosarcoma of the Hip.
AB - The patient was a 27-year-old woman who was being evaluated by a physical
therapist 1 month following a right Achilles tendon repair. She reported the
presence of a painful firm mass in her left hip that she first noticed
approximately 6 months prior. As an initial assessment of the mass, the physical
therapist ordered radiographs of the left hip, which revealed a mass projecting
off the left lateral iliac bone. The radiologist recommended contrast-enhanced
magnetic resonance imaging for further characterization, which revealed a large
lobulated mass that was consistent with an osteochondroma.
PMID- 26424576
TI - Split-belt walking adaptation recalibrates sensorimotor estimates of leg speed
but not position or force.
AB - Motor learning during reaching not only recalibrates movement but can also lead
to small but consistent changes in the sense of arm position. Studies have
suggested that this sensory effect may be the result of recalibration of a
forward model that associates motor commands with their sensory consequences.
Here we investigated whether similar perceptual changes occur in the lower limbs
after learning a new walking pattern on a split-belt treadmill--a task that
critically involves proprioception. Specifically, we studied how this motor
learning task affects perception of leg speed during walking, perception of leg
position during standing or walking, and perception of contact force during
stepping. Our results show that split-belt adaptation leads to robust motor
aftereffects and alters the perception of leg speed during walking. This is
specific to the direction of walking that was trained during adaptation (i.e.,
backward or forward). The change in leg speed perception accounts for roughly
half of the observed motor aftereffect. In contrast, split-belt adaptation does
not alter the perception of leg position during standing or walking and does not
change the perception of stepping force. Our results demonstrate that there is a
recalibration of a sensory percept specific to the domain of the perturbation
that was applied during walking (i.e., speed but not position or force).
Furthermore, the motor and sensory consequences of locomotor adaptation may be
linked, suggesting overlapping mechanisms driving changes in the motor and
sensory domains.
PMID- 26424577
TI - The mammalian efferent vestibular system plays a crucial role in the high
frequency response and short-term adaptation of the vestibuloocular reflex.
AB - Although anatomically well described, the functional role of the mammalian
efferent vestibular system (EVS) remains unclear. Unlike in fish and reptiles,
the mammalian EVS does not seem to play a role in modulation of primary afferent
activity in anticipation of active head movements. However, it could play a role
in modulating long-term mechanisms requiring plasticity such as vestibular
adaptation. We measured the efficacy of vestibuloocular reflex (VOR) adaptation
in alpha9-knockout mice. These mice carry a missense mutation of the gene
encoding the alpha9 nicotinic acetylcholine receptor (nAChR) subunit. The alpha9
nAChR subunit is expressed in the vestibular and auditory periphery, and its loss
of function could compromise peripheral input from the predominantly cholinergic
EVS. We measured the VOR gain (eye velocity/head velocity) in 26 alpha9-knockout
mice and 27 cba129 control mice. Mice were randomly assigned to one of three
groups: gain-increase adaptation (1.5*), gain-decrease adaptation (0.5*), or no
adaptation (baseline, 1*). After adaptation training (horizontal rotations at 0.5
Hz with peak velocity 20 degrees /s), we measured the sinusoidal (0.2-10 Hz, 20
100 degrees /s) and transient (1,500-6,000 degrees /s(2)) VOR in complete
darkness. alpha9-Knockout mice had significantly lower baseline gains compared
with control mice. This difference increased with stimulus frequency (~ 5% <1 Hz
to ~ 25% >1 Hz). Moreover, vestibular adaptation (difference in VOR gain of gain
increase and gain-decrease adaptation groups as % of gain increase) was
significantly reduced in alpha9-knockout mice (17%) compared with control mice
(53%), a reduction of ~ 70%. Our results show that the loss of alpha9 nAChRs
moderately affects the VOR but severely affects VOR adaptation, suggesting that
the EVS plays a crucial role in vestibular plasticity.
PMID- 26424578
TI - Changes in sensory reweighting of proprioceptive information during standing
balance with age and disease.
AB - With sensory reweighting, reliable sensory information is selected over
unreliable information during balance by dynamically combining this information.
We used system identification techniques to show the weight and the adaptive
process of weight change of proprioceptive information during standing balance
with age and specific diseases. Ten healthy young subjects (aged between 20 and
30 yr) and 44 elderly subjects (aged above 65 yr) encompassing 10 healthy
elderly, 10 with cataract, 10 with polyneuropathy, and 14 with impaired balance,
participated in the study. During stance, proprioceptive information of the
ankles was disturbed by rotation of the support surface with specific frequency
content where disturbance amplitude increased over trials. Body sway and reactive
ankle torque were measured to determine sensitivity functions of these responses
to the disturbance amplitude. Model fits resulted in a proprioceptive weight
(changing over trials), time delay, force feedback, reflexive stiffness, and
damping. The proprioceptive weight was higher in healthy elderly compared with
young subjects and higher in elderly subjects with cataract and with impaired
balance compared with healthy elderly subjects. Proprioceptive weight decreased
with increasing disturbance amplitude; decrease was similar in all groups. In all
groups, the time delay was higher and the reflexive stiffness was lower compared
with young or healthy elderly subjects. In conclusion, proprioceptive information
is weighted more with age and in patients with cataract and impaired balance.
With age and specific diseases the time delay was higher and reflexive stiffness
was lower. These results illustrate the opportunity to detect the underlying
cause of impaired balance in the elderly with system identification.
PMID- 26424580
TI - The role of vibration in tactile speed perception.
AB - The relative motion between the surface of an object and our fingers produces
patterns of skin deformation such as stretch, indentation, and vibrations. In
this study, we hypothesized that motion-induced vibrations are combined with
other tactile cues for the discrimination of tactile speed. Specifically, we
hypothesized that vibrations provide a critical cue to tactile speed on surfaces
lacking individually detectable features like dots or ridges. Thus masking
vibrations unrelated to slip motion should impair the discriminability of tactile
speed, and the effect should be surface-dependent. To test this hypothesis, we
measured the precision of participants in discriminating the speed of moving
surfaces having either a fine or a ridged texture, while adding masking vibratory
noise in the working range of the fast-adapting mechanoreceptive afferents.
Vibratory noise significantly reduced the precision of speed discrimination, and
the effect was much stronger on the fine-textured than on the ridged surface. On
both surfaces, masking vibrations at intermediate frequencies of 64 Hz (65-MUm
peak-to-peak amplitude) and 128 Hz (10 MUm) had the strongest effect, followed by
high-frequency vibrations of 256 Hz (1 MUm) and low-frequency vibrations of 32 Hz
(50 and 25 MUm). These results are consistent with our hypothesis that slip
induced vibrations concur to the discrimination of tactile speed.
PMID- 26424579
TI - Spinal electro-magnetic stimulation combined with transgene delivery of
neurotrophin NT-3 and exercise: novel combination therapy for spinal contusion
injury.
AB - Our recent terminal experiments revealed that administration of a single train of
repetitive spinal electromagnetic stimulation (sEMS; 35 min) enhanced synaptic
plasticity in spinal circuitry following lateral hemisection spinal cord injury.
In the current study, we have examined effects of repetitive sEMS applied as a
single train and chronically (5 wk, every other day) following thoracic T10
contusion. Chronic studies involved examination of systematic sEMS administration
alone and combined with exercise training and transgene delivery of neurotrophin
[adeno-associated virus 10-neurotrophin 3 (AAV10-NT3)]. Electrophysiological
intracellular/extracellular recordings, immunohistochemistry, behavioral testing,
and anatomical tracing were performed to assess effects of treatments. We found
that administration of a single sEMS train induced transient facilitation of
transmission through preserved lateral white matter to motoneurons and hindlimb
muscles in chronically contused rats with effects lasting for at least 2 h. These
physiological changes associated with increased immunoreactivity of GluR1 and
GluR2/3 glutamate receptors in lumbar neurons. Systematic administration of sEMS
alone for 5 wk, however, was unable to induce cumulative improvements of
transmission in spinomuscular circuitry or improve impaired motor function
following thoracic contusion. Encouragingly, chronic administration of sEMS,
followed by exercise training (running in an exercise ball and swimming), induced
the following: 1) sustained strengthening of transmission to lumbar motoneurons
and hindlimb muscles, 2) better retrograde transport of anatomical tracer, and 3)
improved locomotor function. Greatest improvements were seen in the group that
received exercise combined with sEMS and AAV-NT3.
PMID- 26424581
TI - Intermanual transfer characteristics of dynamic learning: direction, coordinate
frame, and consolidation of interlimb generalization.
AB - Intermanual transfer, i.e., generalization of motor learning across hands, is a
well-accepted phenomenon of motor learning. Yet, there are open questions
regarding the characteristics of this transfer, particularly the intermanual
transfer of dynamic learning. In this study, we investigated intermanual transfer
in a force field adaptation task concerning the direction and the coordinate
frame of transfer as well as the influence of a 24-h consolidation period on the
transfer. We tested 48 healthy human subjects for transfer from dominant to
nondominant hand, and vice versa. We considered two features of transfer. First,
we examined transfer to the untrained hand using force channel trials that
suppress error feedback and learning mechanisms to assess intermanual transfer in
the form of a practice-dependent bias. Second, we considered transfer by exposing
the subjects to the force field with the untrained hand to check for faster
learning of the dynamics (interlimb savings). Half of the subjects were tested
for transfer immediately after adaptation, whereas the other half were tested
after a 24-h consolidation period. Our results showed intermanual transfer both
from dominant to nondominant hand and vice versa in extrinsic coordinates. After
the consolidation period, transfer effects were weakened. Moreover, the transfer
effects were negligible compared with the subjects' ability to rapidly adapt to
the force field condition. We conclude that intermanual transfer is a
bidirectional phenomenon that vanishes with time. However, the ability to
transfer motor learning seems to play a minor role compared with the rapid
adaptation processes.
PMID- 26424582
TI - A leech model for homeostatic plasticity and motor network recovery after loss of
descending inputs.
AB - Motor networks below the site of spinal cord injury (SCI) and their
reconfiguration after loss of central inputs are poorly understood but remain of
great interest in SCI research. Harley et al. (J Neurophysiol 113: 3610-3622,
2015) report a striking locomotor recovery paradigm in the leech Hirudo verbena
with features that are functionally analogous to SCI. They propose that this well
established neurophysiological system could potentially be repurposed to provide
a complementary model to investigate basic principles of homeostatic compensation
relevant to SCI research.
PMID- 26424583
TI - Associations between fruit and vegetable consumption and psychological distress:
results from a population-based study.
AB - BACKGROUND: Several studies observed associations of various aspects of diet with
mental health, but little is known about the relationship between following the 5
a-day recommendation for fruit and vegetables consumption and mental health.
Thus, we examined the associations of the Swiss daily recommended fruit and
vegetable intake with psychological distress. METHODS: Data from 20,220
individuals aged 15+ years from the 2012 Swiss Health Survey were analyzed. The
recommended portions of fruit and vegetables per day were defined as 5-a-day (at
least 2 portions of fruit and 3 of vegetables). The outcome was perceived
psychological distress over the previous 4 weeks (measured by the 5-item mental
health index [MHI-5]). High distress (MHI-5 score <= 52), moderate distress (MHI
5 > 52 and <= 72) and low distress (MHI-5 > 72 and <= 100) were differentiated
and multinomial logistic regression analyses adjusted for known confounding
factors were performed. RESULTS: The 5-a-day recommendation was met by 11.6 % of
the participants with low distress, 9.3 % of those with moderate distress, and
6.2 % of those with high distress. Consumers fulfilling the 5-a-day
recommendation had lower odds of being highly or moderately distressed than
individuals consuming less fruit and vegetables (moderate vs. low distress: OR =
0.82, 95 % confidence interval [CI] 0.69-0.97; high vs. low distress: OR = 0.55,
95 % CI 0.41-0.75). CONCLUSIONS: Daily intake of 5 servings of fruit and
vegetable was associated with lower psychological distress. Longitudinal studies
are needed to further determine the causal nature of this relationship.
PMID- 26424584
TI - Stable expression and functional characterisation of the diamondback moth
ryanodine receptor G4946E variant conferring resistance to diamide insecticides.
AB - Diamides, such as flubendiamide and chlorantraniliprole, belong to a new chemical
class of insecticides that act as conformation-sensitive activators of insect
ryanodine receptors (RyRs). Both compounds are registered for use against
lepidopteran species such as the diamondback moth, Plutella xylostella, a
notorious global pest of cruciferous crops. Recently acquired resistance to
diamide insecticides in this species is thought to be due to a target-site
mutation conferring an amino acid substitution (G4946E), located within the trans
membrane domain of the RyR, though the exact role of this mutation has not yet
been fully determined. To address this we have cloned a full-length cDNA encoding
the P. xylostella RyR and established clonal Sf9 cell lines stably expressing
either the wildtype RyR or the G4946E variant, in order to test the sensitivity
to flubendiamide and chlorantraniliprole on the recombinant receptor. We report
that the efficacy of both diamides was dramatically reduced in clonal Sf9 cells
stably expressing the G4946E modified RyR, providing clear functional evidence
that the G4946E RyR mutation impairs diamide insecticide binding.
PMID- 26424585
TI - Population Density and Moment-based Approaches to Modeling Domain Calcium
mediated Inactivation of L-type Calcium Channels.
AB - We present a population density and moment-based description of the stochastic
dynamics of domain [Formula: see text]-mediated inactivation of L-type [Formula:
see text] channels. Our approach accounts for the effect of heterogeneity of
local [Formula: see text] signals on whole cell [Formula: see text] currents;
however, in contrast with prior work, e.g., Sherman et al. (Biophys J 58(4):985
995, 1990), we do not assume that [Formula: see text] domain formation and
collapse are fast compared to channel gating. We demonstrate the population
density and moment-based modeling approaches using a 12-state Markov chain model
of an L-type [Formula: see text] channel introduced by Greenstein and Winslow
(Biophys J 83(6):2918-2945, 2002). Simulated whole cell voltage clamp responses
yield an inactivation function for the whole cell [Formula: see text] current
that agrees with the traditional approach when domain dynamics are fast. We
analyze the voltage-dependence of [Formula: see text] inactivation that may occur
via slow heterogeneous domain [[Formula: see text]]. Next, we find that when
channel permeability is held constant, [Formula: see text]-mediated inactivation
of L-type channels increases as the domain time constant increases, because a
slow domain collapse rate leads to increased mean domain [[Formula: see text]]
near open channels; conversely, when the maximum domain [[Formula: see text]] is
held constant, inactivation decreases as the domain time constant increases.
Comparison of simulation results using population densities and moment equations
confirms the computational efficiency of the moment-based approach, and enables
the validation of two distinct methods of truncating and closing the open system
of moment equations. In general, a slow domain time constant requires higher
order moment truncation for agreement between moment-based and population density
simulations.
PMID- 26424586
TI - 8th International Congress of Familial Mediterranean Fever and Systemic
Autoinflammatory Diseases.
PMID- 26424587
TI - The effect of melatonin treatment on postural stability, muscle strength, and
quality of life and sleep in postmenopausal women: a randomized controlled trial.
AB - BACKGROUND: Melatonin is often used as a sleeping aid in elderly adults. As
previous studies suggest a protective role of melatonin against osteoporosis, it
is important to document its safety. Treatment should not cause any hangover
effect that could potentially lead to falls and fractures. We therefore aimed to
evaluate the effect of melatonin on balance- and muscle function. METHODS AND
PATIENTS: In a double-blind placebo-controlled study, we randomized 81
postmenopausal women with osteopenia to receive 1 or 3 mg melatonin, or placebo
nightly for 12 months. Postural balance as well as muscle function was measured.
In addition, we assessed quality of life and sleep at baseline and after 12
months treatment. RESULTS: Compared to placebo, one-year treatment with melatonin
did not affect postural balance or risk of falls. Furthermore, no significant
changes between groups were observed in muscle strength in neither upper- nor
lower extremities. Treatment did not affect quality of life or sleep. However, in
the subgroup of women with sleep disturbances at baseline, a trend towards an
improved sleep quality was seen (p = 0.08). CONCLUSION: Treatment with melatonin
is safe in postmenopausal women with osteopenia. There is no hangover effect
affecting balance- and muscle function following the intake of melatonin. In
women with a good quality of sleep, melatonin has no effect, however in poor
quality of sleep, small doses of melatonin trended towards improving the quality.
TRIAL REGISTRATION: (# NCT01690000).
PMID- 26424588
TI - Fabrication of 3-nm-thick Si3N4 membranes for solid-state nanopores using the
poly-Si sacrificial layer process.
AB - To improve the spatial resolution of solid-state nanopores, thinning the membrane
is a very important issue. The most commonly used membrane material for solid
state nanopores is silicon nitride (Si3N4). However, until now, stable wafer
scale fabrication of Si3N4 membranes with a thickness of less than 5 nm has not
been reported, although a further reduction in thickness is desired to improve
spatial resolution. In the present study, to fabricate thinner Si3N4 membranes
with a thickness of less than 5 nm in a wafer, a new fabrication process that
employs a polycrystalline-Si (poly-Si) sacrificial layer was developed. This
process enables the stable fabrication of Si3N4 membranes with thicknesses of 3
nm. Nanopores were fabricated in the membrane using a transmission electron
microscope (TEM) beam. Based on the relationship between the ionic current
through the nanopores and their diameter, the effective thickness of the
nanopores was estimated to range from 0.6 to 2.2 nm. Moreover, DNA translocation
through the nanopores was observed.
PMID- 26424590
TI - Does the capsaicin-sensitive local neural circuit constitutively regulate vagally
evoked esophageal striated muscle contraction in rats?
AB - To determine whether a capsaicin-sensitive local neural circuit constitutively
modulates vagal neuromuscular transmission in the esophageal striated muscle or
whether the neural circuit operates in a stimulus-dependent manner, we compared
the motility of esophageal preparations isolated from intact rats with those in
which capsaicin-sensitive neurons had been destroyed. Electrical stimulation of
the vagus nerve trunk evoked contractile responses in the esophagus isolated from
a capsaicin-treated rat in a manner similar to those in the esophagus from a
control rat. No obvious differences were observed in the inhibitory effects of D
tubocurarine on intact and capsaicin-treated rat esophageal motility. Destruction
of the capsaicin-sensitive neurons did not significantly affect latency, time to
peak and duration of a vagally evoked twitch-like contraction. These findings
indicate that the capsaicin-sensitive neural circuit does not operate
constitutively but rather is activated in response to an applied stimulus.
PMID- 26424589
TI - Gastrointestinal microbiome modulator improves glucose tolerance in overweight
and obese subjects: A randomized controlled pilot trial.
AB - OBJECTIVE: The objective of this study was to examine the effects of a
gastrointestinal microbiome modulator (GIMM) containing inulin, beta-glucan,
blueberry anthocyanins, and blueberry polyphenols on metabolic parameters, fecal
markers of gut microbiota, and satiety. DESIGN AND METHODS: Thirty overweight or
obese individuals aged 18 to 70years, were enrolled in a randomized controlled
trial. Participants consumed the test product or placebo daily for four weeks.
Stool samples were collected and blood was drawn at baseline and week four for
assessments of gut microbiota, satiety hormones, glucose control, and lipid
measures. Subjective satiety was assessed weekly. Linear models were used to
compare differences from baseline to week four. RESULTS: GIMM consumption
improved blood glucose tolerance (p=0.008), and increased satiety (p=0.03). There
were no statistically significant differences in insulin sensitivity, fecal
markers of gut microbiota, plasma satiety hormones, or serum lipid concentrations
between the groups. However, plasma satiety hormones and fecal short chain fatty
acid concentrations increased in the test group compared to the placebo.
CONCLUSIONS: GIMM consumption for four weeks, increases satiety, and improves
glucose tolerance possibly through insulin-independent pathways.
PMID- 26424591
TI - Changes to the Intestinal Microbiome With Parenteral Nutrition: Review of a
Murine Model and Potential Clinical Implications.
AB - Parenteral nutrition (PN) dependence, while life sustaining, carries a
significant risk of septic complications associated with epithelial barrier
dysfunction and translocation of gut-derived microbiota. Increasing evidence
suggests that PN-associated changes in the intestinal microbiota play a central
role in the breakdown of the intestinal epithelial barrier. This review outlines
the clinical and experimental evidence of epithelial barrier dysfunction with PN,
the role of gut inflammatory dysregulation in driving this process, and the role
of the intestinal microbiome in modulating inflammation in the gut and
systemically. The article summarizes the most current work of our laboratory and
others and describes many of the laboratory findings behind our current
understanding of the PN enteral environment. Understanding the interaction
between nutrient delivery, the intestinal microbiome, and PN-associated
complications may lead to the development of novel therapies to enhance safety
and quality of life for patients requiring PN.
PMID- 26424592
TI - Evidence of cAMP involvement in cellobiohydrolase expression and secretion by
Trichoderma reesei in presence of the inducer sophorose.
AB - BACKGROUND: The signaling second messenger cyclic AMP (cAMP) regulates many
aspects of cellular function in all organisms. Previous studies have suggested a
role for cAMP in the regulation of gene expression of cellulolytic enzymes in
Trichoderma reesei (anamorph of Hypocrea jecorina). METHODS: The effects of cAMP
in T. reesei were analyzed through both activity and expression of cellulase,
intracellular cAMP level measurement, western blotting, indirect
immunofluorescence and confocal microscopy. RESULTS: To elucidate the involvement
of cAMP in the cellulase expression, we analyzed the growth of the mutant strain
?acy1 and its parental strain QM9414 in the presence of the inducers cellulose,
cellobiose, lactose, or sophorose, and the repressor glucose. Our results
indicated that cAMP regulates the expression of cellulase in a carbon source
dependent manner. The expression cel7a, and cel6a genes was higher in the
presence of sophorose than in the presence of cellulose, lactose, cellobiose, or
glucose. Moreover, intracellular levels of cAMP were up to four times higher in
the presence of sophorose compared to other carbon sources. Concomitantly, our
immunofluorescence microscopy and western blot data suggest that in the presence
of sophorose, cAMP may regulate secretion of cellulolytic enzymes in T. reesei.
CONCLUSIONS: These results allow us to better understand the role of cAMP and
expand our knowledge on the signal transduction pathways involved in the
regulation of cellulase expression in T. reesei. Finally, our data may help
develop new strategies to improve the expression of cel7a and cel6a genes, and
therefore, favor their application in several biotechnology fields.
PMID- 26424593
TI - NSAIDs Ibuprofen, Indometacin, and Diclofenac do not interact with Farnesoid X
Receptor.
AB - The nuclear farnesoid X receptor (FXR) is a ligand activated transcription factor
and acts as cellular sensor for bile acids. In this role, FXR is a highly
important liver protector and FXR inhibition by antagonists or knockout has shown
several deleterious effects. A recent report characterized non-steroidal anti
rheumatic drugs (NSAIDs) such as ibuprofen or diclofenac as FXR antagonists and
linked hepatotoxic effects of these drugs with antagonistic activity on FXR.
Since this would guide a way to develop safer anti-inflammatory agents by sparing
FXR, we intended to further characterize the reported antagonistic activity and
intensively investigated ibuprofen, indometacin and diclofenac. However, we
conclude that these agents do not interact with FXR and that the reported reduced
FXR signaling induced by CDCA in presence of NSAIDs is merely a consequence than
a cause of hepatotoxicity.
PMID- 26424595
TI - Transcriptome analysis of Solanum melongena L. (eggplant) fruit to identify
putative allergens and their epitopes.
AB - Eggplant is the third most important Solanaceae crop after tomato and potato,
particularly in India and China. A transcriptome analysis of eggplant's fruit was
performed to study genes involved in medicinal importance and allergies. Illumina
HiSeq 2000 system generated 89,763,638 raw reads (~18 Gb) from eggplant. High
quality reads (59,039,694) obtained after trimming process, were assembled into a
total of 149,224 non redundant set of transcripts. Out of 80,482 annotated
sequences of eggplant fruit (BLASTx results against nr-green plant database),
40,752 transcripts showed significant similarity with predicted proteins of
Solanum tuberosum (51%) followed by Solanum lycopersicum (34%) and other
sequenced plant genomes. With BLASTx top hit analysis against existing allergens,
a total of 1986 homologous allergen sequences were found, which had >37%
similarity with 48 different allergens existing in the database. From the 48
putative allergens, 526 B-cell linear epitopes were identified using BepiPred
linear epitope prediction tool. Transcript sequences generated from this study
can be used to map epitopes of monoclonal antibodies and polyclonal sera from
patients. With the support of this whole transcriptome catalogue of eggplant
fruit, complete list of genes can be predicted based on which secondary
structures of proteins may be modeled.
PMID- 26424594
TI - Depression and suicide ideation in chronic hepatitis C patients untreated and
treated with interferon: prevalence, prevention, and treatment.
AB - Interferon-based therapies were until recently the standard of care in chronic
hepatitis C (CHC), despite their side effects. We aimed to review the available
data on the depression and suicide in CHC patients receiving or not antiviral
therapy based on interferon treatment. A PubMed search was performed, identifying
relevant papers published between 1991 and January 2015 concerning major
depressive disorders and suicidal risk in patients under interferon. A total of
21 relevant papers were retrieved. Prospective studies reported depression as the
most common side effect of interferon, with an incidence peak between weeks 8 and
12 of therapy. Suicide risk was analyzed in 7 of the reviewed articles, and case
reports of attempted suicide were discussed. Moreover, studies have shown that
pretreatment with serotonin reuptake inhibitors is a good strategy for the
prevention of interferon-induced depression.
PMID- 26424596
TI - Frequency of PTEN alterations, TMPRSS2-ERG fusion and their association in
prostate cancer.
AB - BACKGROUND: Phosphatase and tensin homolog (PTEN) gene aberration and trans
membrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26
oncogene homolog (ERG) fusion are the most prevalent genomic events in prostate
cancer. In this study we aimed to evaluate the frequency of PTEN alteration and
TMPRSS2-ERG fusion and possible link between these two biomarkers in Iranian men.
METHODS: We assessed 42 fresh frozen tissue samples of prostate cancer (PCA)
obtained by radical prostatectomy, interrogating the TMPRSS2-ERG fusion gene
along with PTEN gene status using Real Time PCR and FISH methods. RESULTS: Using
Real Time PCR we identified the TMPRSS2-ERG fusion in 64% (27/42) of tumor
samples, which was confirmed by FISH technique, giving 21 positive samples with
deletion, suggesting the presence of TMPRSS2-ERG fusion gene. By contrast, PTEN
deletion was detected in 52% (11/21) of PCA samples, which all showed low
expression in Real Time. Concomitance of PTEN deletion or low expression and
TMPRSS2-ERG fusion was present in PCA samples (P=0.005). All of the PTEN deletion
samples showed TMPRSS2-ERG fusion, (11/11, 100%) while not all of the TMPRSS2-ERG
fusion positive samples showed PTEN deletion. None of 29 cases of BPH and 8 cases
of normal zone of tumor tissue showed TMPRSS2-ERG fusion. CONCLUSIONS: These
results indicate that PTEN loss occurs in cooperation with TMPRSS2-ERG fusion in
PCA. While the majority of PCA samples harbor TMPRSS2-ERG fusion as well as PTEN
gene deletion, normal tissues do not show these molecular aberrations.
PMID- 26424597
TI - Structural signature of Ser83Leu and Asp87Asn mutations in DNA gyrase from
enterotoxigenic Escherichia coli and impact on quinolone resistance.
AB - Enterotoxigenic Escherichia coli (ETEC) is among the most frequent microorganisms
causing traveler's diarrhea (TD). Quinolones are potent antimicrobial agents used
for the treatment of TD. Resistance to quinolones is typically caused by
substitutions in QRDR region of gyrA subunit of DNA gyrase. The aim of this study
was to seek insights into the effect of these substitutions at structural level
and their association with observed quinolone resistance. Majority of the ETEC
strains have gyrA mutations at amino acid position 83 and 87. To understand the
quinolone resistance mechanism at molecular level, we have studied the
interaction of wild type and mutant forms of ETEC gyrA with nalidixic acid and
ciprofloxacin by molecular modeling using Discovery Studio and LeadIt. All the
mutants had reduced affinity towards both ciprofloxacin and nalidixic acid
relative to the wild type due to the mutations introduced in gyrA. Besides Ser83
and Asp87, for nalidixic acid binding Arg91 and His45 residues were observed to
be critical while in ciprofloxacin binding Lys42 and Arg91 residues played a
significant role. Amino acid substitutions contribute to the emergence of drug
resistance in sensitive strains by causing structural alterations leading to
reduced affinity of the drug towards receptor. Analysis of the effect of amino
acid substitutions at structural level is of utmost importance to establish
possible associations between mutations and the diseases. These studies
accelerate the identification of pharmaceutical targets for relevant treatments
and could also be helpful in guiding the design of further experimental research.
PMID- 26424598
TI - Analysis of the coding potential of the ORF in the control region of the female
transmitted Mytilus mtDNA.
AB - Key elements in determining the sex-specific transmission of the female and male
mitochondrial genomes in Mytilus species with doubly uniparental inheritance of
mtDNA are suspected to be contained in the control region. A novel F genome
specific open reading frame (ORF) identified in this region has previously been
hypothesized to be involved in the DUI mechanism. In their recent work Kyriakou
et al. (2014a) questioned the functionality of this ORF. Here, we present
evidence that this ORF is transcribed and may thus code for a functional product.
PMID- 26424599
TI - Top-down and Middle-down Protein Analysis Reveals that Intact and Clipped Human
Histones Differ in Post-translational Modification Patterns.
AB - Post-translational modifications (PTMs) of histone proteins play a fundamental
role in regulation of DNA-templated processes. There is also growing evidence
that proteolytic cleavage of histone N-terminal tails, known as histone clipping,
influences nucleosome dynamics and functional properties. Using top-down and
middle-down protein analysis by mass spectrometry, we report histone H2B and H3 N
terminal tail clipping in human hepatocytes and demonstrate a relationship
between clipping and co-existing PTMs of histone H3. Histones H2B and H3 undergo
proteolytic processing in primary human hepatocytes and the hepatocellular
carcinoma cell line HepG2/C3A when grown in spheroid (3D) culture, but not in a
flat (2D) culture. Using tandem mass spectrometry we localized four different
clipping sites in H3 and one clipping site in H2B. We show that in spheroid
culture clipped H3 proteoforms are mainly represented by canonical histone H3,
whereas in primary hepatocytes over 90% of clipped H3 correspond to the histone
variant H3.3. Comprehensive analysis of histone H3 modifications revealed a
series of PTMs, including K14me1, K27me2/K27me3, and K36me1/me2, which are
differentially abundant in clipped and intact H3. Analysis of co-existing PTMs
revealed negative crosstalk between H3K36 methylation and H3K23 acetylation in
clipped H3. Our data provide the first evidence of histone clipping in human
hepatocytes and demonstrate that clipped H3 carry distinct co-existing PTMs
different from those in intact H3.
PMID- 26424600
TI - Novel Molecular Insights into Classical and Alternative Activation States of
Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture
(SILAC)-based Proteomics.
AB - Microglia, the resident immune cells of the brain, have been shown to display a
complex spectrum of roles that span from neurotrophic to neurotoxic depending on
their activation status. Microglia can be classified into four stages of
activation, M1, which most closely matches the classical (pro-inflammatory)
activation stage, and the alternative activation stages M2a, M2b, and M2c. The
alternative activation stages have not yet been comprehensively analyzed through
unbiased, global-scale protein expression profiling. In this study, BV2 mouse
immortalized microglial cells were stimulated with agonists specific for each of
the four stages and total protein expression for 4644 protein groups was
quantified using SILAC-based proteomic analysis. After validating induction of
the various stages through a targeted cytokine assay and Western blotting of
activation states, the data revealed novel insights into the similarities and
differences between the various states. The data identify several protein groups
whose expression in the anti-inflammatory, pro-healing activation states are
altered presumably to curtail inflammatory activation through differential
protein expression, in the M2a state including CD74, LYN, SQST1, TLR2, and CD14.
The differential expression of these proteins promotes healing, limits
phagocytosis, and limits activation of reactive nitrogen species through toll
like receptor cascades. The M2c state appears to center around the down
regulation of a key member in the formation of actin-rich phagosomes, SLP-76. In
addition, the proteomic data identified a novel activation marker, DAB2, which is
involved in clathrin-mediated endocytosis and is significantly different between
M2a and either M1 or M2b states. Western blot analysis of mouse primary microglia
stimulated with the various agonists of the classical and alternative activation
states revealed a similar trend of DAB2 expression compared with BV2 cells.
PMID- 26424602
TI - Next generation dengue vaccines: A review of the preclinical development
pipeline.
AB - Dengue represents a significant and growing public health problem across the
globe, with approximately half of the world's population at risk. The increasing
and expanding burden of dengue has highlighted the need for new tools to prevent
dengue, including development of dengue vaccines. Recently, the first dengue
vaccine candidate was evaluated in Phase 3 clinical trials, and other vaccine
candidates are under clinical evaluation. There are also a number of candidates
in preclinical development, based on diverse technologies, with promising results
in animal models and likely to move into clinical trials and could eventually be
next-generation dengue vaccines. This review provides an overview of the various
technological approaches to dengue vaccine development with specific focus on
candidates in preclinical development and with evaluation in non-human primates.
PMID- 26424603
TI - A systematic review and meta-analysis of management options for adults who
respond poorly to hepatitis B vaccination.
AB - An estimated 5-10% of adults do not seroconvert after a three-dose primary course
of hepatitis B vaccines, and are considered non-responders. Many approaches have
been used to induce immunity in healthy adult non-responders, but few studies
have compared their relative effectiveness. We conducted a systematic review and
meta-analysis of seroconversion rates after additional doses of four approaches:
20 mcg or 40 mcg intramuscular (IM), and 5 mcg or 20 mcg intradermal (ID). The
search identified 13 articles encompassing 16 studies (N=1067) that met the
eligibility criteria. Seroconversion rates after additional doses of each
approach were pooled and estimated. After one additional dose, the four
approaches produced very similar seroconversion rates and we did not find any
evidence to support the use of 40 mcg IM in healthy adults.
PMID- 26424601
TI - Integrated Metabolomics, Transcriptomics and Proteomics Identifies Metabolic
Pathways Affected by Anaplasma phagocytophilum Infection in Tick Cells.
AB - Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human
granulocytic anaplasmosis. These intracellular bacteria establish infection by
affecting cell function in both the vertebrate host and the tick vector, Ixodes
scapularis. Previous studies have characterized the tick transcriptome and
proteome in response to A. phagocytophilum infection. However, in the postgenomic
era, the integration of omics datasets through a systems biology approach allows
network-based analyses to describe the complexity and functionality of biological
systems such as host-pathogen interactions and the discovery of new targets for
prevention and control of infectious diseases. This study reports the first
systems biology integration of metabolomics, transcriptomics, and proteomics data
to characterize essential metabolic pathways involved in the tick response to A.
phagocytophilum infection. The ISE6 tick cells used in this study constitute a
model for hemocytes involved in pathogen infection and immune response. The
results showed that infection affected protein processing in endoplasmic
reticulum and glucose metabolic pathways in tick cells. These results supported
tick-Anaplasma co-evolution by providing new evidence of how tick cells limit
pathogen infection, while the pathogen benefits from the tick cell response to
establish infection. Additionally, ticks benefit from A. phagocytophilum
infection by increasing survival while pathogens guarantee transmission. The
results suggested that A. phagocytophilum induces protein misfolding to limit the
tick cell response and facilitate infection but requires protein degradation to
prevent ER stress and cell apoptosis to survive in infected cells. Additionally,
A. phagocytophilum may benefit from the tick cell's ability to limit bacterial
infection through PEPCK inhibition leading to decreased glucose metabolism, which
also results in the inhibition of cell apoptosis that increases infection of tick
cells. These results support the use of this experimental approach to
systematically identify cell pathways and molecular mechanisms involved in tick
pathogen interactions. Data are available via ProteomeXchange with identifier
PXD002181.
PMID- 26424604
TI - Immune modulation of T regulatory cells and IgE responses in horses vaccinated
with West Nile virus vaccine combined with a CpG ODN.
AB - Hypersensitivity reactions, such as hives or fatal anaphylactic shock, in
response to vaccination constitute a health hazard for horses that develop
allergies to vaccine components. In such horses vaccination with viral vaccines
stimulates an IgE response to non-target antigens. Viral vaccines share
contaminating non-target proteins, such as bovine serum albumin (BSA); these
antigens can stimulate IgE production with each exposure. We hypothesized that
the addition of a CpG oligodeoxynucleotide (ODN) administered in conjunction with
a West Nile virus vaccine would decrease the IgE response; through up-regulation
of T regulatory cells and T helper 1 cells thus decreasing the potential to
induce a type 1 hypersensitivity response. Thirty adult horses were injected with
either CpG ODN or control GpC ODN with a killed WNV vaccine. T regulatory cell
numbers and BSA specific IgE concentrations were determined pre and post
vaccination. Multicolor flow cytometry was used to evaluate expression of CD4,
CD25, and intracellular Foxp3 on PBMCs. Serum concentrations of BSA specific IgE
were determined by ELISA. Cell culture supernatants from BSA re-stimulated
lymphocytes were evaluated for concentrations of IL-2, IL-4, IL-10, and IFN
gamma. The inclusion of the CpG ODN significantly increased the differentiation
of T regulatory cells in response to antigen in vitro and in vivo. A significant
inverse correlation was found between T regulatory cell numbers and serum BSA
specific IgE concentrations. These results suggest that we can provide a safer
alternate vaccination strategy, particularly for horses that have demonstrated a
pro-allergic phenotype.
PMID- 26424605
TI - Dengue human infection models to advance dengue vaccine development.
AB - Dengue viruses (DENV) currently infect approximately 400 million people each year
causing millions to seek care and overwhelming the health care infrastructure in
endemic areas. Vaccines to prevent dengue and therapeutics to treat dengue are
not currently available. The efficacy of the most advanced candidate vaccine
against symptomatic dengue in general and DENV-2 in particular was much lower
than expected, despite the ability of the vaccine to induce neutralizing antibody
against all four DENV serotypes. Because seroconversion to the DENV serotypes
following vaccination was thought to be indicative of induced protection, these
results have made it more difficult to assess which candidate vaccines should or
should not be evaluated in large studies in endemic areas. A dengue human
infection model (DHIM) could be extremely valuable to down-select candidate
vaccines or therapeutics prior to engaging in efficacy trials in endemic areas.
Two DHIM have been developed to assess the efficacy of live attenuated
tetravalent (LATV) dengue vaccines. The first model, developed by the Laboratory
of Infectious Diseases at the U. S. National Institutes of Health, utilizes a
modified DENV-2 strain DEN2Delta30. This virus was derived from the DENV-2
Tonga/74 that caused only very mild clinical infection during the outbreak from
which it was recovered. DEN2Delta30 induced viremia in 100%, rash in 80%, and
neutropenia in 27% of the 30 subjects to whom it was given. The Walter Reed Army
Institute of Research (WRAIR) is developing a DHIM the goal of which is to
identify DENV that cause symptomatic dengue fever. WRAIR has evaluated seven
viruses and has identified two that meet dengue fever criteria. Both of these
models may be very useful in the evaluation and down-selection of candidate
dengue vaccines and therapeutics.
PMID- 26424606
TI - A bivalent virus-like particle based vaccine induces a balanced antibody response
against both enterovirus 71 and norovirus in mice.
AB - Noroviruses are the main cause of severe viral gastroenteritis, which results in
estimated 200,000 deaths each year, primarily in children in the developing
world. Genogroup II.4 (GII.4) strains are responsible for the majority of
norovirus outbreaks. Enterovirus 71 (EV71), the leading causative agent of hand,
foot and mouth disease, has recently been prevalent in Asia-Pacific regions,
resulting in significant morbidity and mortality in young children. However, no
vaccine is commercially available for either norovirus GII.4 or EV71. Recombinant
virus-like particles (VLPs) derived from either GII.4 or EV71 have been shown to
be promising monovalent vaccine candidates. In this study, we investigate the
possibility to formulate a VLP-based bivalent vaccine for both norovirus GII.4
and EV71. The GII.4- and EV71-VLPs were produced in a baculovirus-insect cell
expression system. A bivalent combination vaccine comprised of GII.4 and EV71
VLPs was formulated and compared with monovalent GII.4- and EV71-VLPs for their
immunogenicity in mice. We found that the bivalent vaccine elicited durable
antibody responses toward both GII.4 and EV71, and the antibody titers were
comparable to that induced by the monovalent vaccines, indicating there is no
immunological interference between the two antigens in the combination vaccine.
More significantly, the bivalent vaccine-immunized mouse sera could efficiently
neutralize EV71 infection and block GII.4-VLP binding to mucin. Together, our
results demonstrate that the experimental combination vaccine comprised of GII.4
and EV71-VLPs is able to induce a balanced protective antibody response, and
therefore strongly support further preclinical and clinical development of such a
bivalent VLP vaccine targeting both norovirus GII.4 and EV71.
PMID- 26424607
TI - Text message reminders for timely routine MMR vaccination: A randomized
controlled trial.
AB - OBJECTIVE: Measles-mumps-rubella (MMR) vaccination is important for preventing
disease outbreaks, yet pockets of under-vaccination persist. Text message
reminders have been employed successfully for other pediatric vaccines, but
studies examining their use for MMR vaccination are limited. This study assessed
the impact of text message reminders on timely MMR vaccination. STUDY DESIGN:
Parents (n=2054) of 9.5-10.5-month-old children from four urban academically
affiliated pediatric clinics were randomized to scheduling plus appointment text
message reminders, appointment text message reminder-only, or usual care. The
former included up to three text reminders to schedule the one-year preventive
care visit. Both text messaging arms included a text reminder sent 2 days before
that visit. Outcomes included appointment scheduling, appointment attendance, and
MMR vaccination by age 13 months, the standard of care at study sites. RESULTS:
Children of parents in the scheduling plus appointment text message reminders arm
were more likely to have a scheduled one-year visit than those in the other arms
(71.9% vs. 67.4%, relative risk ratio (RRR) 1.07 [95% CI 1.005-1.13]),
particularly if no appointment was scheduled before randomization (i.e., no
baseline appointment) (62.1% vs. 54.7%, RRR 1.14 [95% CI 1.04-1.24]). One-year
visit attendance and timely MMR vaccination were similar between arms. However,
among children without a baseline appointment, those with parents in the
scheduling plus appointment text message reminders arm were more likely to
undergo timely MMR vaccination (61.1% vs. 55.1%, RRR 1.11 [95% CI 1.01-1.21]).
CONCLUSION: Text message reminders improved timely MMR vaccination of high-risk
children without a baseline one-year visit.
PMID- 26424608
TI - Dietary glutamine supplementation effects on amino acid metabolism, intestinal
nutrient absorption capacity and antioxidant response of gilthead sea bream
(Sparus aurata) juveniles.
AB - A study was undertaken to evaluate dietary glutamine supplementation effects on
gilthead sea bream performance, intestinal nutrient absorption capacity, hepatic
and intestinal glutamine metabolism and oxidative status. For that purpose
gilthead sea bream juveniles (mean weight 13.0g) were fed four isolipidic (18%
lipid) and isonitrogenous (43% protein) diets supplemented with 0, 0.5, 1 and 2%
glutamine for 6weeks. Fish performance, body composition and intestinal nutrient
absorption capacity were not affected by dietary glutamine levels. Hepatic and
intestinal glutaminase (GlNase), glutamine synthetase (GSase), alanine
aminotransferase, aspartate aminotransferase and glutamate dehydrogenase
activities were also unaffected by dietary glutamine supplementation. In the
intestine GlNase activity was higher and GSase/GlNase ratio was two-fold lower
than in the liver, suggesting a higher use of glutamine for energy production by
the intestine than by the liver. The liver showed higher catalase and glucose-6
phosphate dehydrogenase activities, while the intestine presented higher
glutathione peroxidase and glutathione reductase activities and oxidised
glutathione content, which seems to reveal a higher glutathione dependency of the
intestinal antioxidant response. Total and reduced glutathione contents in liver
and intestine and superoxide dismutase activity in the intestine were enhanced by
dietary glutamine, though lipid peroxidation values were not affected. Overall,
differences between liver and intestine glutamine metabolism and antioxidant
response were identified and the potential of dietary glutamine supplementation
to gilthead sea bream's antioxidant response was elucidated.
PMID- 26424610
TI - Authors' reply to Whitlock and Saied and colleagues.
PMID- 26424609
TI - Improving wound healing and preventing surgical site complications of closed
surgical incisions: a possible role of Incisional Negative Pressure Wound
Therapy. A systematic review of the literature.
AB - Advances in preoperative care, surgical techniques and technologies have enabled
surgeons to achieve primary closure in a high percentage of surgical procedures.
However, often, underlying patient comorbidities in addition to surgical-related
factors make the management of surgical wounds primary closure challenging
because of the higher risk of developing complications. To date, extensive
evidence exists, which demonstrate the benefits of negative pressure dressing in
the treatment of open wounds; recently, Incisional Negative Pressure Wound
Therapy (INPWT) technology as delivered by PrevenaTM (KCI USA, Inc., San Antonio,
TX) and Pico (Smith & Nephew Inc, Andover, MA) systems has been the focus of a
new investigation on possible prophylactic measures to prevent complications via
application immediately after surgery in high-risk, clean, closed surgical
incisions. A systematic review was performed to evaluate INPWT's effect on
surgical sites healing by primary intention. The primary outcomes of interest are
an understanding of INPWT functioning and mechanisms of action, extrapolated from
animal and biomedical engineering studies and incidence of complications
(infection, dehiscence, seroma, hematoma, skin and fat necrosis, skin and fascial
dehiscence or blistering) and other variables influenced by applying INPWT (re
operation and re-hospitalization rates, time to dry wound, cost saving)
extrapolated from human studies. A search was conducted for published articles in
various databases including PubMed, Google Scholar and Scopus Database from 2006
to March 2014. Supplemental searches were performed using reference lists and
conference proceedings. Studies selection was based on predetermined inclusion
and exclusion criteria and data extraction regarding study quality, model
investigated, epidemiological and clinical characteristics and type of surgery,
and the outcomes were applied to all the articles included. 1 biomedical
engineering study, 2 animal studies, 15 human studies for a total of 6 randomized
controlled trials, 5 prospective cohort studies, 7 retrospective analyses, were
included. Human studies investigated the outcomes of 1042 incisions on 1003
patients. The literature shows a decrease in the incidence of infection, sero
haematoma formation and on the re-operation rates when using INPWT. Lower level
of evidence was found on dehiscence, decreased in some studies, and was
inconsistent to make a conclusion. Because of limited studies, it is difficult to
make any assertions on the other variables, suggesting a requirement for further
studies for proper recommendations on INPWT.
PMID- 26424611
TI - Direct chemotherapeutic dual drug delivery through intra-articular injection for
synergistic enhancement of rheumatoid arthritis treatment.
AB - The effectiveness of systemic rheumatoid arthritis (RA) treatments is limited by
difficulties in achieving therapeutic doses within articular joints. We evaluated
the ability of intra-articular administration of injectable formulations to
synergistically enhance repair of RA joints. Methotrexate-loaded hyaluronic acid
(Met-HA), dexamethasone-loaded microcapsules (Dex-M), and Dex-M dispersed inside
Met-HA were prepared as viscous emulsions and injected into articular joints
using a needle to form a drug depot. By near-infrared (NIR) fluorescence imaging,
we confirmed the local release of NIR from the depot injected into the articular
joint over an extended period. In comparison with the subjects treated with Met
HA or Dex-M alone, subjects treated simultaneously with Met-HA and Dex-M
exhibited faster and more significant RA repair. Collectively, these results
indicated that the drug depot formed after intra-articular injection of Met
HA/Dex-M induced long-lasting drug release and allowed Met and Dex to effectively
act in the articular joint, resulting in enhanced RA repair.
PMID- 26424613
TI - Mandatory submission of patient identifiable information to third parties: FGM
now, what next?
PMID- 26424612
TI - Identification of the centromeric repeat in the threespine stickleback fish
(Gasterosteus aculeatus).
AB - Centromere sequences exist as gaps in many genome assemblies due to their
repetitive nature. Here we take an unbiased approach utilizing centromere protein
A (CENP-A) chomatin immunoprecipitation followed by high-throughput sequencing to
identify the centromeric repeat sequence in the threespine stickleback fish
(Gasterosteus aculeatus). A 186-bp, AT-rich repeat was validated as centromeric
using both fluorescence in situ hybridization (FISH) and immunofluorescence
combined with FISH (IF-FISH) on interphase nuclei and metaphase spreads. This
repeat hybridizes strongly to the centromere on all chromosomes, with the
exception of weak hybridization to the Y chromosome. Together, our work provides
the first validated sequence information for the threespine stickleback
centromere.
PMID- 26424614
TI - Hemoperitoneum Due to Left Inferior Phrenic Artery Injury During
Pericardiocentesis.
PMID- 26424616
TI - Epidural abscess from prolotherapy: a cautionary tale.
PMID- 26424615
TI - Properties of ATP-gated ion channels assembled from P2X2 subunits in mouse
cochlear Reissner's membrane epithelial cells.
AB - In the cochlea, Reissner's membrane separates the scala media endolymphatic
compartment that sustains the positive endocochlear potential and ion composition
necessary for sound transduction, from the scala vestibuli perilymphatic
compartment. It is known that with sustained elevated sound levels, adenosine 5'
triphosphate (ATP) is released into the endolymph and ATP-gated ion channels on
the epithelial cells lining the endolymphatic compartment shunt the
electrochemical driving force, contributing to protective purinergic hearing
adaptation. This study characterises the properties of epithelial cell P2X(2)
type ATP-activated membrane conductance in the mouse Reissner's membrane, which
forms a substantial fraction of the scale media surface. The cells were found to
express two isoforms (a and b) of the P2X(2) subunit arising from alternative
splicing of the messenger RNA (mRNA) transcript that could contribute to the
trimeric subunit assembly. The ATP-activated conductance demonstrated both
immediate and delayed desensitisation consistent with incorporation of the
combination of P2X(2) subunit isoforms. Activation by the ATP analogue 2meSATP
had equipotency to ATP, whereas alpha,beta-meATP and adenosine 5'-diphosphate
(ADP) were ineffective. Positive allosteric modulation of the P2X(2) channels by
protons was profound. This native conductance was blocked by the P2X(2)-selective
blocker pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) and the
conductance was absent in these cells isolated from mice null for the P2rX2 gene
encoding the P2X(2) receptor subunit. The activation and desensitisation
properties of the Reissner's membrane epithelial cell ATP-gated P2X(2) channels
likely contribute to the sensitivity and kinetics of purinergic control of the
electrochemical driving force for sound transduction invoked by noise exposure.
PMID- 26424617
TI - Retinal and choroidal alterations in patients with anorexia nervosa without
vision loss.
AB - OBJECTIVE: Evaluate the alterations of retinal anatomy and function, as well as
choroidal thickness changes, in patients with anorexia nervosa (AN). METHOD: 13
female AN patients (26 eyes) and 20 female controls (40 eyes) were included.
Assessment of the retinal and choroidal anatomy was performed by optical
coherence-tomography, while multifocal-electroretinogram was used for
measurements of the electrical activity of the macula. Statistical analysis was
performed using t-test. RESULTS: Central macular thickness was found to be
thinner in AN (140.04 +/- 14.45, 150.85 +/- 16.03, p = 0.007), likewise the
ganglion cell complex and outer retinal layer (ORL) at most areas. ORL superiorly
was thicker in AN (169.12 +/- 2.55, 163.00 +/- 8.70, p < 0.001), while retinal
nerve fiber layer was not different between the two groups, except the inferior
region (121.08 +/- 18.52, 137.60 +/- 7.30, p < 0.001). Choroidal thickness was
evenly diminished in the anorectic group (p = 0.001-0.027). Multifocal
electroretinogram showed lower P1-retinal response density amplitude of ring 1 in
AN (159.04 +/- 60.83, 292.43 +/- 11.59, p < 0.001), but no significant difference
concerning the P1-response density amplitude of ring 2 (79.04 +/- 21.89, 82.63 +/
9.10, p = 0.36). DISCUSSION: In AN patients, even without vision loss,
significant changes occur in retinal and choroidal thickness, as well as in the
electrical activity of the macula. However, this is a pilot study in a small
sample that needs replication.
PMID- 26424618
TI - Next-generation sequencing (NGS) in the identification of encephalitis-causing
viruses: Unexpected detection of human herpesvirus 1 while searching for RNA
pathogens.
AB - BACKGROUND: Encephalitis is a severe neurological syndrome usually caused by
viruses. Despite significant progress in diagnostic techniques, the causative
agent remains unidentified in the majority of cases. The aim of the present study
was to test an alternative approach for the detection of putative pathogens in
encephalitis using next-generation sequencing (NGS). METHODS: RNA was extracted
from cerebrospinal fluid (CSF) from a 60-year-old male patient with encephalitis
and subjected to isothermal linear nucleic acid amplification (Ribo-SPIA, NuGen)
followed by next-generation sequencing using MiSeq (Illumina) system and
metagenomics data analysis. RESULTS: The sequencing run yielded 1,578,856 reads
overall and 2579 reads matched human herpesvirus I (HHV-1) genome; the presence
of this pathogen in CSF was confirmed by specific PCR. In subsequent experiments
we found that the DNAse I treatment, while lowering the background of host
derived sequences, lowered the number of detectable HHV-1 sequences by a factor
of 4. Furthermore, we found that the routine extraction of total RNA by the
Chomczynski method could be used for identification of both DNA and RNA pathogens
in typical clinical settings, as it results in retention of a significant amount
of DNA. CONCLUSION: In summary, it seems that NGS preceded by nucleic acid
amplification could supplement currently used diagnostic methods in encephalitis.
PMID- 26424620
TI - Graphitic Carbon Nitride Polymers toward Sustainable Photoredox Catalysis.
AB - As a promising two-dimensional conjugated polymer, graphitic carbon nitride (g-C3
N4 ) has been utilized as a low-cost, robust, metal-free, and visible-light
active photocatalyst in the field of solar energy conversion. This Review mainly
describes the latest advances in g-C3 N4 photocatalysts for water splitting.
Their application in CO2 conversion, organosynthesis, and environmental
purification is also briefly discussed. The methods to modify the electronic
structure, nanostructure, crystal structure, and heterostructure of g-C3 N4 ,
together with correlations between its structure and performance are illustrated.
Perspectives on the challenges and opportunities for the future exploration of g
C3 N4 photocatalysts are provided. This Review will promote the utilization of g
C3 N4 materials in the fields of photocatalysis, energy conversion, environmental
remediation, and sensors.
PMID- 26424619
TI - Assembly and characterization of gp160-nanodiscs: A new platform for biochemical
characterization of HIV envelope spikes.
AB - The human immunodeficiency virus (HIV) is the causative agent of acquired immune
deficiency syndrome (AIDS) and is thus responsible for significant morbidity and
mortality worldwide. Despite considerable effort, preparation of an effective
vaccine for AIDS has been elusive and it has become clear that a fundamental
understanding of the relevant antigenic targets on HIV is essential. The Env
trimer spike is the only viral antigen present on the surface of the viral
particle and it is the target of all broadly neutralizing antibodies isolated to
date. Thus, a soluble, homogeneous, and well-defined preparation of Env trimers
is an important first step toward biochemical and structural characterization of
the antigenic spike. Phospholipid bilayer nanodiscs represent a relatively new
technology that can serve as a platform for the assembly of membrane proteins
into a native membrane-like environment. Here we describe the preparation and
characterization of unprocessed full-length, natively glycoslyated gp160 Env
proteins incorporated into nanodiscs (gp160-ND). The particles are soluble and
well defined in the absence of detergent, and possess a morphology anticipated of
Env incorporated into a lipid ND. Importantly, the gp160-NDs retain CD4 and Env
antibody binding characteristics expected of a functional trimer spike and their
incorporation into a lipid membrane allows interrogation of epitopes associated
with the membrane-proximal ectodomain region of gp41. These studies provide the
groundwork for the use of gp160-ND in more detailed biochemical and structural
studies that may set the stage for their use in vaccine development.
PMID- 26424621
TI - Malaria Chemoprophylaxis and Self-Reported Impact on Ability to Work: Mefloquine
Versus Doxycycline.
AB - BACKGROUND: It is well known that both mefloquine and doxycycline are commonly
associated with adverse effects when taken for malaria chemoprophylaxis. However,
the relative impact of these on travelers' ability to work is not so well
understood. The aim of this study was to identify which drug has a lesser impact
on the ability to work as measured by self-reported severity of adverse effects
via a questionnaire. METHODS: This was a questionnaire-based two-arm cohort
study. Participants were soldiers selected from 10 consecutive units training in
Kenya during 2012 and 2013. The exposure was either doxycycline or mefloquine and
the main outcome measure was impact upon ability to work. Each cohort was advised
to take doxycycline or mefloquine with exceptions at the individual level where
medically or occupationally advised. RESULTS: Significantly more (p < 0.0001)
doxycycline users reported that one or more adverse effects had interfered with
their ability to do their job than mefloquine users. Of the 867 mefloquine users,
who reported on the impact of adverse effects, 109 (12.6%) reported that one or
more adverse effects had impacted upon their ability to do their job, compared to
152 (22.2%) of the 685 doxycycline users who had reported on the impact of any
adverse effects. Doxycycline symptoms were predominantly gastrointestinal and
dermatological, whereas mefloquine symptoms were neuropsychiatric. CONCLUSIONS:
Self-reported symptoms were common in those that responded and, while the true
background rate of adverse effects (off any medication) is unknown, doxycycline
had a significantly increased rate compared with mefloquine and was associated
with a greater occupational impact. Therefore, this study supports the view that,
for organizations which provide malaria chemoprophylaxis to employees free of
charge, mefloquine should be the first-choice antimalarial drug where the only
alternative is doxycycline.
PMID- 26424622
TI - Abnormal heart rate recovery in patients with heart failure: an important target
for exercise training treatment.
PMID- 26424623
TI - Vitamin D and heart: A not so sunny pathway.
PMID- 26424624
TI - Achilles' heel of coil occlusion procedure: Anticoagulant therapy.
PMID- 26424625
TI - Transcatheter ventricular septal defect closure: Should we feel comfortable after
many years?
PMID- 26424626
TI - Squeezed heart.
PMID- 26424627
TI - Is echocardiographic epicardial adipose tissue thickness measurement a reliable
and reproducible method for risk stratification?
PMID- 26424628
TI - What is the real predictive value of red cell distribution width for the
mortality in non-ST elevation acute coronary syndrome?
PMID- 26424629
TI - Arterial stiffness evaluation in patients with irritable bowel syndrome: Role of
antihypertensive drugs and statins.
PMID- 26424630
TI - Can epicardial adipose tissue predict coronary artery plaque?
PMID- 26424631
TI - Preoperative oral pentoxifylline in case of coronary artery bypass grafting with
left ventricular dysfunction (ejection fraction equal to/less than 30%).
PMID- 26424632
TI - Cardiogenic shock due to occlusion of left main coronary in a cocaine user.
PMID- 26424633
TI - An alternative malpractice system suggestion for Turkey: Patient compensation
system.
PMID- 26424634
TI - Clopidogrel and morphine: Aggregation disturbance?
PMID- 26424635
TI - Interview with Carlo Di Mario.
PMID- 26424637
TI - A case of an atypically located cardiac hydatid cyst.
PMID- 26424638
TI - An unpredictable complication of a transcatheter closure device and surgical
treatment.
PMID- 26424640
TI - Why and How Epstein-Barr Virus Was Discovered 50 Years Ago.
AB - An account is given of the experiences and events which led to a search being
undertaken for a causative virus in the recently described Burkitt's lymphoma and
of the steps which ultimately culminated in the discovery of the new human
herpesvirus which came to be known as Epstein-Barr virus (EBV).
PMID- 26424641
TI - Tumor Associations of EBV--Historical Perspectives.
AB - This is a brief history of our collaborative work with Werner and Gertrude Henle,
Francis Wiener, George and Yanke Manolov, and others on the association of
Epstein-Barr virus (EBV) with Burkitt lymphoma and other human tumors. Special
emphasis is put on the question where EBV is a true cancer virus.
PMID- 26424639
TI - Enhancing assertive community treatment with cognitive behavioral social skills
training for schizophrenia: study protocol for a randomized controlled trial.
AB - BACKGROUND: Schizophrenia leads to profound disability in everyday functioning
(e.g., difficulty finding and maintaining employment, housing, and personal
relationships). Medications can effectively reduce positive symptoms (e.g.,
hallucinations and delusions), but they do not meaningfully improve daily life
functioning. Psychosocial evidence-based practices (EBPs) improve functioning,
but these EBPs are not available to most people with schizophrenia. The field
must close the research and service delivery gap by adapting EBPs for
schizophrenia to facilitate widespread implementation in community settings. Our
hybrid effectiveness and implementation study represents an initiative to bridge
this divide. In this study we will test whether an existing EBP (i.e., Cognitive
Behavioral Social Skills Training (CBSST)) modified to work in practice settings
(i.e., Assertive Community Treatment (ACT) teams) commonly available to persons
with schizophrenia results in better consumer outcomes. We will also identify key
factors relevant to developing future CBSST implementation strategies.
METHODS/DESIGN: For the effectiveness study component, persons with schizophrenia
will be recruited from existing publicly funded ACT teams operating in community
settings. Participants will be randomized to one of the 2 treatments (ACT alone
or ACT + Adapted CBSST) and followed longitudinally for 18 months with
assessments every 18 weeks after baseline (5 in total). The primary outcome
domain is psychosocial functioning (e.g., everyday living skills and activities
related to employment, education, and housing) as measured by self-report,
testing, and observation. Additional outcome domains of interest include
mediators of change in functioning, symptoms, and quality of services. Primary
analyses will be conducted using linear mixed-effects models for continuous data.
The implementation study component consists of a structured, mixed qualitative
quantitative methodology (i.e., Concept Mapping) to characterize and assess the
implementation experience from multiple stakeholder perspectives in order to
inform future implementation initiatives. DISCUSSION: Adapting CBSST to fit into
the ACT service delivery context found throughout the United States creates an
opportunity to substantially increase the number of persons with schizophrenia
who could have access to and benefit from EBPs. As part of the implementation
learning process training materials and treatment workbooks have been revised to
promote easier use of CBSST in the context of brief community-based ACT visits.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02254733 . Date of registration: 25
April 2014.
PMID- 26424642
TI - EBV-Specific Immune Response: Early Research and Personal Reminiscences.
AB - Early research on Epstein-Barr virus (EBV) developed from serological
observations that were made soon after the discovery of the virus. Indeed, the
definition of the humoral response to a variety of EBV proteins dominated the
early literature and was instrumental in providing the key evidence for the
association of the virus with infectious mononucleosis (IM), Burkitt's lymphoma
(BL), and nasopharyngeal carcinoma (NPC). Each of these disease associations
involved a distinct pattern of serological reactivity to the EBV membrane
antigens (MA), early antigens (EA), and the EBV nuclear antigen (EBNA). When it
became generally accepted that the marked lymphocytosis , which is a hallmark of
acute IM, was dominated by T cells, considerable effort was directed toward
untangling the specificities that might be associated with restricting the
proliferation of newly infected B cells. Early evidence was divided between
support for both EBV non-specific and/or HLA non-restricted components. However,
all results needed to be reassessed in light of the observation that T cells died
by apoptosis within hours of separation from fresh blood from acute IM patients.
The observation that EBV-infected cultures from immune (but not non-immune)
individuals began to die (termed regression) about 10 days post-seeding, provided
the first evidence of a specific memory response which was apparently capable of
controlling the small pool of latently infected B cells which all immune
individuals possess. In this early era, CD8(+) T cells were thought to be the
effector population responsible for this phenomenon, but later studies suggested
a role for CD4(+) cells. This historical review includes reference to key early
observations in regard to both the specific humoral and cellular responses to EBV
infection from the time of the discovery of the virus until 1990. As well, we
have included personal recollections in regard to the events surrounding the
discovery of the memory T cell response since we believe they add a human
dimension to a chapter focussed on early history.
PMID- 26424643
TI - Epstein-Barr Virus Strain Variation.
AB - What is wild-type Epstein-Barr virus and are there genetic differences in EBV
strains that contribute to some of the EBV-associated diseases? Recent progress
in DNA sequencing has resulted in many new Epstein-Barr virus (EBV) genome
sequences becoming available. EBV isolates worldwide can be grouped into type 1
and type 2, a classification based on the EBNA2 gene sequence. Type 1 transforms
human B cells into lymphoblastoid cell lines much more efficiently than type 2
EBV and molecular mechanisms that may account for this difference in cell
transformation are now becoming understood. Study of geographic variation of EBV
strains independent of the type 1/type 2 classification and systematic
investigation of the relationship between viral strains, infection and disease
are now becoming possible. So we should consider more directly whether viral
sequence variation might play a role in the incidence of some EBV-associated
diseases.
PMID- 26424644
TI - Chromatin Structure of Epstein-Barr Virus Latent Episomes.
AB - EBV latent infection is characterized by a highly restricted pattern of viral
gene expression. EBV can establish latent infections in multiple different tissue
types with remarkable variation and plasticity in viral transcription and
replication. During latency, the viral genome persists as a multi-copy episome, a
non-integrated-closed circular DNA with nucleosome structure similar to cellular
chromosomes. Chromatin assembly and histone modifications contribute to the
regulation of viral gene expression, DNA replication, and episome persistence
during latency. This review focuses on how EBV latency is regulated by chromatin
and its associated processes.
PMID- 26424645
TI - The Epigenetic Life Cycle of Epstein-Barr Virus.
AB - Ever since the discovery of Epstein-Barr virus (EBV) more than 50 years ago, this
virus has been studied for its capacity to readily establish a latent infection,
which is the prominent hallmark of this member of the herpesvirus family. EBV has
become an important model for many aspects of herpesviral latency, but the
molecular steps and mechanisms that lead to and promote viral latency have only
emerged recently. It now appears that the virus exploits diverse facets of
epigenetic gene regulation in the cellular host to establish a latent infection.
Most viral genes are transcriptionally repressed, and viral chromatin is densely
compacted during EBV's latent phase, but latent infection is not a dead end. In
order to escape from this phase, epigenetic silencing must be reverted
efficiently and quickly. It appears that EBV has perfected a clever strategy to
overcome transcriptional repression of its many lytic genes to initiate virus de
novo synthesis within a few hours after induction of its lytic cycle. This review
tries to summarize the known molecular mechanisms, the current models, concepts,
and ideas underlying this viral strategy. This review also attempts to identify
and address gaps in our current understanding of EBV's epigenetic mechanisms
within the infected cellular host.
PMID- 26424646
TI - Epstein-Barr Virus: From the Detection of Sequence Polymorphisms to the
Recognition of Viral Types.
AB - The Epstein-Barr virus is etiologically linked with the development of benign and
malignant diseases, characterized by their diversity and a heterogeneous
geographic distribution across the world. The virus possesses a 170-kb-large
genome that encodes for multiple proteins and non-coding RNAs. Early on there
have been numerous attempts to link particular diseases with particular EBV
strains, or at least with viral genetic polymorphisms. This has given rise to a
wealth of information whose value has been difficult to evaluate for at least
four reasons. First, most studies have looked only at one particular gene and
missed the global picture. Second, they usually have not studied sufficient
numbers of diseased and control cases to reach robust statistical significance.
Third, the functional significance of most polymorphisms has remained unclear,
although there are exceptions such as the 30-bp deletion in LMP1. Fourth,
different biological properties of the virus do not necessarily equate with a
different pathogenicity. This was best illustrated by the type 1 and type 2
viruses that markedly differ in terms of their transformation abilities, yet do
not seem to cause different diseases. Reciprocally, environmental and genetic
factors in the host are likely to influence the outcome of infections with the
same virus type. However, with recent developments in recombinant virus
technology and in the availability of high throughput sequencing, the tide is now
turning. The availability of 23 complete or nearly complete genomes has led to
the recognition of viral subtypes, some of which possess nearly identical
genotypes. Furthermore, there is growing evidence that some genetic polymorphisms
among EBV strains markedly influence the biological and clinical behavior of the
virus. Some virus strains are endowed with biological properties that explain
crucial clinical features of patients with EBV-associated diseases. Although we
now have a better overview of the genetic diversity within EBV genomes, it has
also become clear that defining phenotypic traits evinced by cells infected by
different viruses usually result from the combination of multiple polymorphisms
that will be difficult to identify in their entirety. However, the steadily
increasing number of sequenced EBV genomes and cloned EBV BACS from diseased and
healthy patients will facilitate the identification of the key polymorphisms that
condition the biological and clinical behavior of the viruses. This will allow
the development of preventative and therapeutic approaches against highly
pathogenic viral strains.
PMID- 26424649
TI - Primary Immunodeficiencies Associated with EBV Disease.
AB - Epstein-Barr virus (EBV) infects nearly all humans and usually is asymptomatic,
or in the case of adolescents and young adults, it can result in infectious
mononucleosis. EBV-infected B cells are controlled primarily by NK cells, iNKT
cells, CD4 T cells, and CD8 T cells. While mutations in proteins important for B
cell function can affect EBV infection of these cells, these mutations do not
result in severe EBV infection. Some genetic disorders affecting T and NK cell
function result in failure to control EBV infection, but do not result in
increased susceptibility to other virus infections. These include mutations in
SH2D1A, BIRC4, ITK, CD27, MAGT1, CORO1A, and LRBA. Since EBV is the only virus
that induces proliferation of B cells, the study of these diseases has helped to
identify proteins critical for interactions of T and/or NK cells with B cells.
Mutations in three genes associated with hemophagocytic lymphohistocytosis, PRF1,
STXBP2, and UNC13D, can also predispose to severe chronic active EBV disease.
Severe EBV infection can be associated with immunodeficiencies that also
predispose to other viral infections and in some cases other bacterial and fungal
infections. These include diseases due to mutations in PIK3CD, PIK3R1, CTPS1,
STK4, GATA2, MCM4, FCGR3A, CARD11, ATM, and WAS. In addition, patients with
severe combined immunodeficiency, which can be due to mutations in a number of
different genes, are at high risk for various infections as well as EBV B cell
lymphomas. Identification of proteins important for control of EBV may help to
identify new targets for immunosuppressive therapies.
PMID- 26424650
TI - Burkitt's Lymphoma.
AB - Endemic Burkitt's lymphoma (BL) remains the most prevalent pediatric cancer in
sub-Saharan Africa even though it was the first human cancer with a viral
etiology described over 50 years ago. Epstein-Barr virus (EBV) was discovered in
a BL tumor in 1964 and has since been implicated in other malignancies. The
etiology of endemic BL has been linked to EBV and Plasmodium falciparum malaria
co-infection. While epidemiologic studies have yielded insight into EBV infection
and the etiology of endemic BL, the modulation of viral persistence in children
by malaria and deficits in EBV immunosurveillance has more recently been reified.
Renewed efforts to design prophylactic and therapeutic EBV vaccines provide hope
of preventing EBV-associated BL as well as increasing the ability to cure this
cancer.
PMID- 26424648
TI - Infectious Mononucleosis.
AB - Infectious mononucleosis is a clinical entity characterized by sore throat,
cervical lymph node enlargement, fatigue, and fever most often seen in
adolescents and young adults and lasting several weeks. It can be caused by a
number of pathogens, but this chapter only discusses infectious mononucleosis due
to primary Epstein-Barr virus (EBV) infection. EBV is a gamma-herpesvirus that
infects at least 90% of the population worldwide. The virus is spread by intimate
oral contact among teenagers and young adults. How preadolescents acquire the
virus is not known. A typical clinical picture with a positive heterophile test
is usually sufficient to make the diagnosis, but heterophile antibodies are not
specific and do not develop in some patients. EBV-specific antibody profiles are
the best choice for staging EBV infection. In addition to causing acute illness,
there can also be long-term consequences as the result of acquisition of the
virus. Several EBV-related illnesses occur including certain cancers and
autoimmune diseases, as well as complications of primary immunodeficiency in
persons with the certain genetic mutations. A major obstacle to understanding
these sequelae has been the lack of an efficient animal model for EBV infection,
although progress in primate and mouse models has recently been made. Key future
challenges are to develop protective vaccines and effective treatment regimens.
PMID- 26424651
TI - Contribution of the Epstein-Barr Virus to the Pathogenesis of Hodgkin Lymphoma.
AB - The morphology of the pathognomonic Hodgkin and Reed-Sternberg cells (HRS) of
Hodgkin lymphoma was described over a century ago, yet it was only relatively
recently that the B-cell origin of these cells was identified. In a proportion of
cases, HRS cells harbour monoclonal forms of the B lymphotropic Epstein-Barr
virus (EBV). This review summarises current knowledge of the pathogenesis of
Hodgkin lymphoma with a particular emphasis on the contribution of EBV.
PMID- 26424647
TI - EBV Persistence--Introducing the Virus.
AB - Persistent infection by EBV is explained by the germinal center model (GCM) which
provides a satisfying and currently the only explanation for EBVs disparate
biology. Since the GCM touches on every aspect of the virus, this chapter will
serve as an introduction to the subsequent chapters. EBV is B lymphotropic, and
its biology closely follows that of normal mature B lymphocytes. The virus
persists quiescently in resting memory B cells for the lifetime of the host in a
non-pathogenic state that is also invisible to the immune response. To access
this compartment, the virus infects naive B cells in the lymphoepithelium of the
tonsils and activates these cells using the growth transcription program. These
cells migrate to the GC where they switch to a more limited transcription
program, the default program, which helps rescue them into the memory compartment
where the virus persists. For egress, the infected memory cells return to the
lymphoepithelium where they occasionally differentiate into plasma cells
activating viral replication. The released virus can either infect more naive B
cells or be amplified in the epithelium for shedding. This cycle of infection and
the quiescent state in memory B cells allow for lifetime persistence at a very
low level that is remarkably stable over time. Mathematically, this is a stable
fixed point where the mechanisms regulating persistence drive the state back to
equilibrium when perturbed. This is the GCM of EBV persistence. Other possible
sites and mechanisms of persistence will also be discussed.
PMID- 26424652
TI - The Role of EBV in the Pathogenesis of Diffuse Large B Cell Lymphoma.
AB - Epstein-Barr virus (EBV) infection is a common feature of B cell
lymphoproliferative disorders (LPDs), including diffuse large B cell lymphoma.
Approximately 10 % of DLBCLs are EBV-positive, with the highest incidence in
immunocompromised and elderly patients. Here, we review the clinical, genetic,
and pathologic characteristics of DLBCL and discuss the molecular role of EBV in
lymphoma tumorigenesis. Using EBV-positive DLBCL of the elderly as a model, we
describe the key features of EBV-positive DLBCL. Studies of EBV-positive DLBCL of
the elderly demonstrate that EBV-positive DLBCL has a distinct biology, related
to both viral and host factors. The pathogenic mechanisms noted in EBV-positive
DLBCL of the elderly, including enhanced NFkappaB activity, are likely to be a
generalizable feature of EBV-positive DLBCL. Therefore, we review how this
information might be used to target the EBV or its host response for the
development of novel treatment strategies.
PMID- 26424653
TI - Nasopharyngeal Carcinoma: An Evolving Role for the Epstein-Barr Virus.
AB - The Epstein-Barr herpesvirus (EBV) is an important human pathogen that is closely
linked to several major malignancies including the major epithelial tumor,
undifferentiated nasopharyngeal carcinoma (NPC). This important tumor occurs with
elevated incidence in specific areas, particularly in southern China but also in
Mediterranean Africa and some regions of the Middle East. Regardless of tumor
prevalence, undifferentiated NPC is consistently associated with EBV. The
consistent detection of EBV in all cases of NPC, the maintenance of the viral
genome in every cell, and the continued expression of viral gene products suggest
that EBV is a necessary factor for the malignant growth in vivo. However, the
molecular characterization of the infection and identification of critical events
have been hampered by the difficulty in developing in vitro models of NPC.
Epithelial cell infection is difficult in vitro and in contrast to B-cell
infection does not result in immortalization and transformation. Cell lines
established from NPC usually do not retain the genome, and the successful
establishment of tumor xenografts is difficult. However, critical genetic changes
that contribute to the onset and progression of NPC and key molecular properties
of the viral genes expressed in NPC have been identified. In some cases, viral
expression becomes increasingly restricted during tumor progression and tumor
cells may express only the viral nuclear antigen EBNA1 and viral noncoding RNAs.
As NPC develops in the immunocompetent, the continued progression of deregulated
growth likely reflects the combination of expression of viral oncogenes in some
cells and viral noncoding RNAs that likely function synergistically with changes
in cellular RNA and miRNA expression.
PMID- 26424654
TI - EBV and Autoimmunity.
AB - Although a role of EBV in autoimmunity is biologically plausible and evidence of
altered immune responses to EBV is abundant in several autoimmune diseases,
inference on causality requires the determination that disease risk is higher in
individuals infected with EBV than in those uninfected and that in the latter it
increases following EBV infection. This determination has so far been possible
only for multiple sclerosis (MS) and, to some extent, for systemic lupus
erythematosus (SLE), whereas evidence is either lacking or not supportive for
other autoimmune conditions. In this chapter, we present the main epidemiological
findings that justify the conclusion that EBV is a component cause of MS and SLE
and possible mechanisms underlying these effects.
PMID- 26424655
TI - Incidence and predictors of annual chlamydia testing among 15-29 year olds
attending Aboriginal primary health care services in New South Wales, Australia.
AB - BACKGROUND: For the past two decades, chlamydia has been the most commonly
notified infectious disease among young people (15-29 year olds) in Australia,
the United States of America and the United Kingdom and rates have increased
annually in these three countries. In Australia, rates of chlamydia are three
times higher in Aboriginal compared with non-Aboriginal people. Australian
sexually transmissible infection guidelines recommend annual chlamydia testing
for 15-29 year old females and males. This analysis will examine the incidence
and predictors of annual chlamydia testing in 15-29 year olds attending four
Aboriginal Community Controlled Health Services (ACCHS) in Australia. METHODS:
From 2009-2011, attendance and chlamydia testing data were extracted from the
patient system to calculate the number and proportion of 15-29 year olds that
were tested for chlamydia and that tested positive for chlamydia by gender (male,
female), age-group (15-19, 20-24, 25-29 years), Aboriginal status (Aboriginal,
non-Aboriginal people) and by the four ACCHSs sites (1, 2, 3 and 4). A cohort was
created to calculate the incidence rate per 100 person-years (PY) and predictors
of an annual chlamydia test (a test within 12-months of a previous test/visit) by
the above factors using Cox regression. Unadjusted and adjusted hazard ratios
(AHR) and their 95 % confidence intervals (CIs) and p-values were calculated with
significance at p < 0.05. RESULTS: From 2009-2011, there were 2896 individuals
who attended the four ACCHSs. Overall , 17 % (22 % of females and 10 % of males)
were tested for chlamydia and 9 % tested positive (8 % of females and 14 % of
males). The median time to an annual chlamydia test was 10.7 months. The cohort
included 2318 individuals. Overall the incidence rate of an annual chlamydia test
was 9.1 per 100 PY (11.6 in females and 5.8 in males). Predictors of an annual
chlamydia test were being female (AHR: 1.7, 95 % CI: 1.2-2.2, p < 0.01), being 15
19 years old (AHR: 1.6, 95 % CI: 1.1-2.3, p < 0.01) and attending ACCHS site 2
(AHR: 3.8, 95 % CI: 1.8-8.0, p < 0.01). CONCLUSIONS: This analysis highlights
that opportunistic STI testing strategies are needed to increase annual chlamydia
testing in young people; especially males.
PMID- 26424656
TI - A good patient? How notions of 'a good patient' affect patient-nurse
relationships and ART adherence in Zimbabwe.
AB - BACKGROUND: While patient-provider interactions are commonly understood as
mutually constructed relationships, the role of patient behaviour, participation
in interactions, and characteristics, particularly ideals surrounding notions of
'good' and 'bad' patients, are under-examined. This article examines social
representations of 'a good patient' and how these representations affect patient
healthcare provider relationships and antiretroviral treatment (ART) for people
living with HIV. METHODS: Using thematic network analysis, we examined interview
and focus group transcripts involving 25 healthcare staff, 48 ART users, and 31
carers of HIV positive children, as well as field notes from over 100 h of
ethnographic observation at health centres in rural Zimbabwe. RESULTS:
Characteristics of a good patient include obedience, patience, politeness,
listening, enthusiasm for treatment, intelligence, physical cleanliness, honesty,
gratitude and lifestyle adaptations (taking pills correctly and coming to the
clinic when told). As healthcare workers may decide to punish patients who do not
live up the 'good patient persona', many patients seek to perform within the
confines of the 'good patient persona' to access good care and ensure continued
access to ART. DISCUSSION: The notion of a 'good ART patient' can have positive
effects on patient health outcomes. It is one of the only arenas of the clinic
experience that ART patients can influence in their favour. However, for people
not conforming to the norms of the 'good patient persona', the productive and
health-enabling patient-nurse relationship may break down and be detrimental to
the patient. CONCLUSION: We conclude that policy makers need to take heed of the
social representations that govern patient-nurse relationships and their role in
facilitating or undermining ART adherence.
PMID- 26424657
TI - The regulatory role of B cells in autoimmunity, infections and cancer:
Perspectives beyond IL10 production.
AB - The term regulatory B cells (B regs) is ascribed to a heterogeneous population of
B cells with the function of suppressing inflammatory responses. They have been
described mainly during the last decade in the context of different immune
mediated diseases. Most of the work on B regs has been focused on IL-10-producing
B cells. However, B cells can exert regulatory functions independently of IL-10
production. Here we discuss the phenotypes, development and effector mechanisms
of B regs and advances in their role in autoimmunity, infections and cancer.
PMID- 26424658
TI - The zinc-finger protein SPT4 interacts with SPT5L/KTF1 and modulates
transcriptional silencing in Arabidopsis.
AB - The Arabidopsis multidomain protein SPT5L/KTF1 (which has similarity to the
transcript elongation factor SPT5) associates with RNA polymerase V (RNAPV) and
is an accessory factor in RNA-directed DNA methylation. The zinc-finger protein
SPT4 was found to interact with SPT5L (and SPT5) both in vivo and in vitro. Here,
we show that plants depleted of SPT4 relative to wild type display reduced DNA
methylation and the locus specificity is shared with SPT5L, suggesting a
cooperation of SPT4 and SPT5L. Unlike observed for SPT5, no reduced protein level
of SPT5L is determined in SPT4-deficient plants. These experiments demonstrate
that in addition to the RNA polymerase II-associated SPT4/SPT5 that is generally
conserved in eukaryotes, flowering plants have SPT4/SPT5L that is involved in
RNAPV-mediated transcriptional silencing.
PMID- 26424659
TI - O-Fucosylation of CCN1 is required for its secretion.
AB - The matricellular protein CCN1, also known as Cyr61, is a secreted ligand and has
numerous functions. Human CCN1 contains one predicted O-fucosylation site in the
thrombospondin type-1 repeat (TSR1) domain at Thr(242). In this report, we
demonstrated that CCN1 is O-fucosylated at Thr(242) using mass spectrometry.
Deficiency of O-fucosylation resulted in the decrement of the cell surface
localization and the secretion of CCN1. Furthermore, knockdown of protein O
fucosyltransferase 2, which modifies a specific Ser/Thr residue in the TSR1
domain, decreased secreted levels of CCN1. These results demonstrated that O
fucosylation of CCN1 at Thr(242) regulates its secretion.
PMID- 26424660
TI - Disease-modifying effects of phosphocitrate and phosphocitrate-beta-ethyl ester
on partial meniscectomy-induced osteoarthritis.
AB - BACKGROUND: It is believed that phosphocitrate (PC) exerts its disease-modifying
effects on osteoarthritis (OA) by inhibiting the formation of crystals. However,
recent findings suggest that PC exerts its disease-modifying effect, at least in
part, through a crystal-independent action. This study sought to examine the
disease-modifying effects of PC and its analogue PC-beta-ethyl ester (PC-E) on
partial meniscectomy-induced OA and the structure-activity relationship. METHODS:
Calcification- and proliferation-inhibitory activities were examined in OA
fibroblast-like synoviocytes (FLSs) culture. Disease-modifying effects were
examined using Hartley guinea pigs undergoing partial meniscectomy. Cartilage
degeneration was examined with Indian ink, safranin-O, and picrosirius red.
Levels of matrix metalloproteinase-13 (MMP-13), ADAM metallopeptidase with
thrombospondin type 1 motif 5 (ADAMTS5), chemokine (C-C motif) ligand 5 (CCL5),
and cyclooxygenase-2 (Cox-2) were examined with immunostaining. The effects of PC
E and PC on gene expressions in OA FLSs were examined with microarray. Results
are expressed as mean +/- standard deviation and analyzed using Student's t test
or Wilcoxon rank sum test. RESULTS: PC-E was slightly less powerful than PC as a
calcification inhibitor but as powerful as PC in the inhibition of OA FLSs
proliferation. PC significantly inhibited cartilage degeneration in the partial
meniscectomied right knee. PC-E was less powerful than PC as a disease-modifying
drug, especially in the inhibition of cartilage degeneration in the non-operated
left knee. PC significantly reduced the levels of ADAMTS5, MMP-13 and CCL5,
whereas PC-E reduced the levels of ADAMTS5 and CCL5. Microarray analyses revealed
that PC-E failed to downregulate the expression of many PC-downregulated genes
classified in angiogenesis and inflammatory response. CONCLUSIONS: PC is a
disease-modifying drug for posttraumatic OA therapy. PC exerts its disease
modifying effect through two independent actions: inhibiting pathological
calcification and modulating the expression of many genes implicated in OA. The
beta-carboxyl group of PC plays an important role in the inhibition of cartilage
degeneration, little role in the inhibition of FLSs proliferation, and a moderate
role in the inhibition of FLSs-mediated calcification.
PMID- 26424661
TI - Osteochondroma of the fifth rib resulting in recurrent hemothorax.
AB - A 48-year-old man presented with recurrent spontaneous hemothoraces, which
ultimately were found to be secondary to a pedunculated costal osteochondroma
causing vascular injury. After initially undergoing endovascular coil
embolization, he ultimately required segmental rib resection containing the
offending lesion for definite treatment. Although a few cases of symptomatic
costal osteochondromas have been reported in the literature, as far as we know,
no previous reports have provided direct radiologic confirmation of active
bleeding or the role of angiographic intervention. In this report, we highlight
the importance of CT angiography in establishing a direct link between an
osteochondroma and recurrent hemothorax. We also discuss the diagnostic imaging
challenges associated with this condition and the use of a multidisciplinary
treatment strategy involving both angiographic and operative management.
PMID- 26424662
TI - Developing a system to monitor family planning and HIV service integration:
results from a pilot test of indicators.
AB - OBJECTIVES: To determine the feasibility of collecting data to calculate six
indicators of family planning (FP) and HIV integration using existing health
information systems (HIS); obtain information to refine indicators; and identify
changes needed in existing HIS to calculate indicators. DESIGN: Data abstraction
from HIS in a purposive sample of 39 health facilities in Ethiopia, Rwanda,
Tanzania and Uganda to analyse data availability and quality undertaken between
November 2010 and March 2011. METHODS: Teams reviewed patient record cards,
registers, monthly and quarterly reports for the most recent complete month.
Teams recorded all possible sources for each data element, indicated whether data
are collated monthly, and whether disaggregation by age, sex and originating
service was possible. RESULTS: With the exception of Uganda, all countries were
able to report the proportion of service delivery points offering integrated
services. Ethiopia was able to calculate the indicator for fixed sites but not
for home-based care services. In most cases we were able to calculate the
proportion of HIV clients receiving FP services or referral, and the proportion
of FP clients receiving an HIV test or referral. It is feasible to collect data
for these indicators under current circumstances in some countries. CONCLUSIONS:
Several actions are proposed for national health systems, including adopting a
system of unique client identifiers. Age group reporting bands should be aligned
across services. More accurate counts of daily and active client loads are needed
to provide programme managers with information to inform programme monitoring.
PMID- 26424663
TI - Equine Embryo Sexing and Ultrasonographic Foetal Sexing - Interests and
Applicability.
AB - The ability to choose the sex of the offspring is of upmost economic importance
for horse breeders. Unlike other species, horses present several reproductive
peculiarities that interfere with assisted reproductive technologies used in
other large animals (such as bovine) and make them difficult to apply. Thus,
there is a great interest to determine the sex of the offspring as soon as
possible. This has led to the development of several technologies to serve this
purpose, which can be classified into two categories. One is equine embryo sexing
by either non-invasive biotechnological methods, such as monitoring of X-linked
enzymes before X chromosome inactivation and detection of sex-specific antigen,
or by invasive biotechnological methods, such as cytogenetic analysis and
polymerase chain reaction (PCR). The other one is equine foetus sexing using
ultrasound scanning in different stages of its development (early, mid or late),
by different approaches (transrectally or transabdominally). This can be
performed with classic B-mode ultrasound machines or using 3D-mode and Doppler
mode scanners. This review article offers a comprehensive overview of the current
status of these procedures as well as an assessment of their interests and
applicability.
PMID- 26424664
TI - Concepts and Molecular Aspects in the Polypharmacology of PARP-1 Inhibitors.
AB - Recent years have witnessed a renewed interest in PARP-1 inhibitors as promising
anticancer agents with multifaceted functions. Particularly exciting developments
include the approval of olaparib (Lynparza) for the treatment of refractory
ovarian cancer in patients with BRCA1/2 mutations, and the increasing
understanding of the polypharmacology of PARP-1 inhibitors. The aim of this
review article is to provide the reader with a comprehensive overview of the
distinct levels of the polypharmacology of PARP-1 inhibitors, including 1) inter
family polypharmacology, 2) intra-family polypharmacology, and 3) multi-signaling
polypharmacology. Progress made in gaining insight into the molecular basis of
these multiple target-independent and target-dependent activities of PARP-1
inhibitors are discussed, with an outlook on the potential impact that a better
understanding of polypharmacology may have in aiding the explanation as to why
some drug candidates work better than others in clinical settings, albeit acting
on the same target with similar inhibitory potency.
PMID- 26424666
TI - Co-ingestion of energy drinks with alcohol and other substances among a sample of
people who regularly use ecstasy.
AB - INTRODUCTION AND AIMS: Despite the potential harms of mixing unregulated drugs
with energy drinks (ED), research to date has primarily been focused on EDs co
ingested with alcohol. Consequently, the aim of the present study was to explore
the rate of use, harms and correlates of EDs co-ingested with alcohol and other
drugs among a sample of people who regularly use illicit stimulant drugs. DESIGN
AND METHODS: In 2010, 693 Australians who regularly used ecstasy completed a 1-h
interview about their past six-month ED and drug use. RESULTS: Three-quarters of
the sample (77%) had recently consumed EDs with other substances, primarily
alcohol (70%) and ecstasy (57%). People who consumed ED with alcohol versus those
who had consumed ED with ecstasy and with alcohol (only 8% reported only
consuming ED with ecstasy) had similar profiles in regards to demographics, drug
use, mental health and drug-related problems. Primary motives for consuming ED
with alcohol included increased alertness (59%), the taste (25%), to party for
longer (23%) and to combat fatigue (16%). One-half (52%) and one-quarter (27%) of
participants who consumed EDs with alcohol and with ecstasy respectively had
recently experienced adverse outcomes post-consumption, primarily headaches (24%
and 11%) and heart palpitations (21% and 14%). DISCUSSION AND CONCLUSIONS: Co
ingestion of EDs with licit and illicit drugs is common among people who
regularly use ecstasy and related drugs. Adverse outcomes of co-ingestion suggest
that targeted education regarding negative interactive drug effects is crucial
for harm reduction. [Peacock A, Sindicich N, Dunn M, Whittaker E, Sutherland R,
Entwistle G, Burns L, Bruno R. Co-Ingestion of Energy Drinks with Alcohol and
Other Substances among a Sample of People Who Regularly Use Ecstasy. Drug Alcohol
Rev 2016;35:352-358].
PMID- 26424667
TI - Antiretroviral gels: facing the FACTS.
PMID- 26424665
TI - A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers
in Idiopathic Inflammatory Myopathy.
AB - Autoantibodies specific for idiopathic inflammatory myopathy (myositis-specific
autoantibodies (MSAs)) are clinically useful biomarkers to help the diagnosis of
polymyositis/dermatomyositis (PM/DM). Many of these are also associated with a
unique clinical subset of PM/DM, making them useful in predicting and monitoring
certain clinical manifestations. Classic MSAs known for over 30 years include
antibodies to Jo-1 (histidyl transfer RNA (tRNA) synthetase) and other aminoacyl
tRNA synthetases (ARS), anti-Mi-2, and anti-signal recognition particle (SRP).
Anti-Jo-1 is the first autoantibodies to ARS detected in 15-25 % of patients. In
addition to anti-Jo-1, antibodies to seven other aminoacyl tRNA synthetases (ARS)
have been reported with prevalence, usually 1-5 % or lower. Patients with any
anti-ARS antibodies are associated with anti-synthetase syndrome characterized by
myositis, interstitial lung disease (ILD), arthritis, Raynaud's phenomenon, and
others. Several recent studies suggested heterogeneity in clinical features among
different anti-ARS antibody-positive patients and anti-ARS may also be found in
idiopathic ILD without myositis. Anti-Mi-2 is a classic marker for DM and
associated with good response to steroid treatment and good prognosis. Anti-SRP
is specific for PM and associated with treatment-resistant myopathy
histologically characterized as necrotizing myopathy. In addition to classic
MSAs, several new autoantibodies with strong clinical significance have been
described in DM. Antibodies to transcription intermediary factor 1gamma/alpha
(TIF1gamma/alpha, p155/140) are frequently found in DM associated with malignancy
while anti-melanoma differentiation-associated gene 5 (MDA5; CADM140) are
associated with clinically amyopathic DM (CADM) complicated by rapidly
progressive ILD. Also, anti-MJ/nuclear matrix protein 2 (NXP-2) and anti-small
ubiquitin-like modifier-1 (SUMO-1) activating enzyme (SAE) are recognized as new
DM-specific autoantibodies. Addition of these new antibodies to clinical practice
in the future will help in making earlier and more accurate diagnoses and better
management for patients.
PMID- 26424668
TI - FLAMINGO: still in the pink?
PMID- 26424669
TI - Co-trimoxazole prophylaxis: the debates continue.
PMID- 26424670
TI - Maintenance of antiretroviral efficacy in children.
PMID- 26424671
TI - Cost-effectiveness of community-based strategies for HIV.
PMID- 26424672
TI - Viral co-infections in high-risk communities of Pakistan.
PMID- 26424674
TI - Co-trimoxazole prophylaxis in adults, including pregnant women, with HIV: a
systematic review and meta-analysis.
AB - INTRODUCTION: Co-trimoxazole prophylaxis is used to reduce morbidity and
mortality in people with HIV. We systematically reviewed three topics related to
co-trimoxazole prophylaxis to update WHO guidelines: initiation, discontinuation,
and dose. METHODS: We searched PubMed, Embase, WHO Global Index Medicus, and
clinical trial registries in November, 2013, for randomised controlled trials and
observational studies including co-trimoxazole prophylaxis and a comparator
group. Studies were eligible if they reported death, WHO clinical stage 3 or 4
events, admittance to hospital, severe bacterial infections, tuberculosis,
pneumonia, diarrhoea, malaria, or treatment-limiting adverse events. Infant
mortality, low birthweight, and placental malaria were additional outcomes for
the comparison of co-trimoxazole prophylaxis and intermittent preventive
treatment for malaria in pregnant women (IPTp). We compared a dose of 480 mg co
trimoxazole once a day with one of 960 mg co-trimoxazole once a day. We used a
10% margin for non-inferiority and equivalence analyses. We used random-effects
models for all meta-analyses. This study is registered with PROSPERO, number
CRD42014007163. FINDINGS: 19 articles, published from 1995 to 2014 and including
35 328 participants, met the inclusion criteria. Co-trimoxazole prophylaxis
reduced rates of death (hazard ratio [HR] 0.40, 95% CI 0.26-0.64) when started at
CD4 counts of 350 cells per MUL or lower with antiretroviral therapy (ART)
worldwide. Co-trimoxazole prophylaxis started at higher than 350 cells per MUL
without ART reduced rates of death (0.50, 0.30-0.83) and malaria (0.25, 0.10
0.57) in Africa. Co-trimoxazole prophylaxis was non-inferior to IPTp with respect
to infant mortality (risk difference [RD] -0.05, 95% CI -0.12 to 0.02), low
birthweight (0.00, -0.07 to 0.07), and placental malaria (0.00, -0.10 to 0.10).
Co-trimoxazole prophylaxis continuation after ART-induced recovery with CD4
counts higher than 350 cells per MUL reduced admittances to hospital (HR 0.42,
95% CI 0.22-0.80), pneumonia (0.73, 0.61-0.88), malaria (0.03, 0.01-0.10), and
diarrhoea (0.61, 0.48-0.78) in Africa. A dose of 480 mg co-trimoxazole
prophylaxis once a day did not reduce treatment-limiting adverse events compared
with 960 mg once a day (RD -0.07, 95% CI -0.52 to 0.39). INTERPRETATION: Co
trimoxazole prophylaxis should be given with ART in people with CD4 counts of 350
cells per MUL or lower in low-income and middle-income countries. Co-trimoxazole
prophylaxis should be provided irrespective of CD4 count in settings with a high
burden of infectious diseases. Pregnant women with HIV in Africa should use co
trimoxazole rather than IPTp to prevent malaria complications in infants. Further
research is needed to inform dose optimisation and co-trimoxazole use in the
context of expanded ART in different epidemiological settings. FUNDING: None.
PMID- 26424675
TI - Role of Amylin in Type 1 and Type 2 Diabetes.
AB - PURPOSE: The pathophysiology of diabetes has historically focused on alterations
in insulin secretion and function; however, diabetes involves multiple hormonal
alterations, including abnormal regulation of amylin. This review discusses the
physiologic functions of amylin in glucose homeostasis and the rationale for
amylin replacement in type 1 and 2 diabetes. The use of pramlintide, a synthetic
amylin analog, is also discussed. CONCLUSIONS: Amylin, formed primarily in
pancreatic islet beta cells, is cosecreted with insulin in response to caloric
intake. Patients with type 1 diabetes have lower baseline amylin serum
concentrations, and amylin response to caloric intake is absent. Patients with
type 2 diabetes requiring insulin also have a diminished amylin response to
caloric intake, potentially related to the degree of beta-cell impairment. Key
physiologic functions of amylin in maintaining glucose homeostasis include
suppressing glucagon release in response to caloric intake, delaying the rate of
gastric emptying, and stimulating the satiety center in the brain to limit
caloric intake. Pramlintide is indicated for adults with type 1 and 2 diabetes
who have not achieved adequate glucose control despite optimal insulin therapy.
As an adjunct to insulin therapy, pramlintide demonstrated significant reductions
in A1C in patients with type 1 and 2 diabetes, with favorable effects on body
weight. It is administered subcutaneously before each major meal. There is an
increased risk of hypoglycemia with insulin when used in combination with
pramlintide. Other adverse effects may include nausea, vomiting, anorexia,
reduced appetite, and headache. Proper patient selection and education are
essential to successful pramlintide use.
PMID- 26424673
TI - Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive
adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open
label, phase 3b study.
AB - BACKGROUND: The primary analysis of the FLAMINGO study at 48 weeks showed that
patients taking dolutegravir once daily had a significantly higher virological
response rate than did those taking ritonavir-boosted darunavir once daily, with
similar tolerability. We present secondary efficacy and safety results analysed
at 96 weeks. METHODS: FLAMINGO was a multicentre, open-label, phase 3b, non
inferiority study of HIV-1-infected treatment-naive adults. Patients were
randomly assigned (1:1) to dolutegravir 50 mg or darunavir 800 mg plus ritonavir
100 mg, with investigator-selected combination tenofovir and emtricitabine or
combination abacavir and lamivudine background treatment. The main endpoints were
plasma HIV-1 RNA less than 50 copies per mL and safety. The non-inferiority
margin was -12%. If the lower end of the 95% CI was greater than 0%, then we
concluded that dolutegravir was superior to ritonavir-boosted darunavir. This
trial is registered with ClinicalTrials.gov, number NCT01449929. FINDINGS: Of 595
patients screened, 488 were randomly assigned and 484 included in the analysis
(242 assigned to receive dolutegravir and 242 assigned to receive ritonavir
boosted darunavir). At 96 weeks, 194 (80%) of 242 patients in the dolutegravir
group and 164 (68%) of 242 in the ritonavir-boosted darunavir group had HIV-1 RNA
less than 50 copies per mL (adjusted difference 12.4, 95% CI 4.7-20.2; p=0.002),
with the greatest difference in patients with high viral load at baseline (50/61
[82%] vs 32/61 [52%], homogeneity test p=0.014). Six participants (three since 48
weeks) in the dolutegravir group and 13 (four) in the darunavir plus ritonavir
group discontinued because of adverse events. The most common drug-related
adverse events were diarrhoea (23/242 [10%] in the dolutegravir group vs 57/242
[24%] in the darunavir plus ritonavir group), nausea (31/242 [13%] vs 34/242
[14%]), and headache (17/242 [7%] vs 12/242 [5%]). INTERPRETATION: Once-daily
dolutegravir is associated with a higher virological response rate than is once
daily ritonavir-boosted darunavir. Dolutegravir compares favourably in efficacy
and safety to a boosted darunavir regimen with nucleoside reverse transcriptase
inhibitor background treatment for HIV-1-infected treatment-naive patients.
FUNDING: ViiV Healthcare and Shionogi & Co.
PMID- 26424676
TI - Diabetes Education as a Career Choice.
AB - PURPOSE: The purpose of the study was to examine the field of diabetes education
along with identifying facilitators and barriers for future health care
professionals entering the specialty field of diabetes education. METHOD: Faculty
members who were currently teaching in a health-related discipline, the students
of those faculty members, and nursing students who were members of the National
Student Nursing Association were surveyed to gather descriptive data. RESULTS:
While faculty members reported they are promoting diabetes education to their
health professions students, many nursing students are not aware of this career
path. Nursing students understand that diabetes is a significant problem and will
be something they encounter in all areas of their careers, but many were not sure
they wanted to specialize in it. CONCLUSIONS: There is a gap between what faculty
members and students report as far as awareness of the diabetes education
specialty. In addition, misinformation about diabetes and people living with
diabetes may be a deterrent for potential future diabetes educators. American
Association of Diabetes Educators, health professions faculty members, and
practicing diabetes educators can do more to clear up misconceptions and promote
diabetes education as a career path for students in the health professions.
PMID- 26424677
TI - Grandparent Education Through Simulation-Diabetes.
AB - PURPOSE: The purpose of this study was to explore the feasibility of using human
patient simulation (HPS) to teach type 1 diabetes (T1DM) management to
grandparents of grandchildren with T1DM. METHODS: Thirty grandparents (11 male,
19 female) of young grandchildren (aged 12 and under) with T1DM were recruited
from an urban medical center. Experimental group (n = 14) grandparents received
hands-on visual T1DM management education using an HPS intervention, and control
group (n = 16) grandparents received similar education using a non-HPS
intervention. FINDINGS: This study demonstrated the feasibility of recruiting and
retaining grandparents into a clinical trial using HPS to teach T1DM management.
Post intervention, all grandparent scores for T1DM knowledge, confidence, and
fear showed significant improvement from time 1 to time 2, with HPS group
grandparent scores showing consistently larger improvement. CONCLUSIONS: The
consistency of larger HPS-taught grandparent score improvement is suggestive of a
benefit for the HPS teaching method. Early multimethod Certified Diabetes
Educator (CDE)-provided T1DM education is an important point of entry for
inducting grandparent members onto the grandchild's diabetes care team.
PMID- 26424679
TI - Transcatheter aortic valve implantation for paradoxical low-flow low-gradient
aortic stenosis patients.
AB - OBJECTIVES: We compared the outcomes of transcatheter aortic valve implantation
(TAVI) in three different aortic stenosis syndromes: paradoxical low-flow low
gradient aortic stenosis (PLFLG), high-gradient aortic stenosis (HGAS), and low
ejection fraction low-gradient severe aortic stenosis (LEF-LG). BACKGROUND:
Outcomes for PLFLG patients after TAVI procedure are not well known. METHODS:
Between 2010 and 2013, patients with severe (indexed aortic valve area iAVA<=0.6
cm(2)/m(2)) symptomatic aortic stenosis were consecutively referred to our
institution for TAVI because of multiple comorbidities and excessive surgical
risk. About 262 patients were split into three groups as following, PLFLG: mean
gradient MG<=40 mm Hg, stroke volume index SVI<=35 mL/m(2), ejection fraction
EF>=55%, valvuloarterial impedance Zva>4.5 mm Hg/mL/m(2), maximal aortic jet
velocity MaxV<4 m/s; LEF-LG: MG<=40 mm Hg, MaxV<4 m/s, EF<=50%, SVI<=35 mL/m(2);
and HGAS: MaxV>4 m/s, MG>40 mm Hg, EF>55%. The primary endpoint of our study was
to evaluate mid-term global and cardiovascular mortalities; secondary endpoints
included recommended VARC-2 variables. RESULTS: PLFLG (n = 31) mid-term survival
was similar to HGAS (n = 172) (mean follow-up = 13.2 months [4.6-26]). Conversely
LEF-LG patients (n = 59) displayed significant higher rates of all-cause (P =
0.01) and cardiovascular mortalities (P = 0.05). Postprocedural outcomes (VARC-2
criteria) were similar in the PLFLG and HGAS groups except regarding major
bleeding (P = 0.02), while the LEF-LG group had more congestive heart failure and
a higher BNP before discharge (both P < 0.001) than the other groups. 30-days
deaths were significantly more frequent in LEF-LG and PLFLG in comparison to HGAS
(P = 0.03). CONCLUSION: As opposed to LEF-LG patients, mid-term prognosis after
TAVI procedure in PLFLG patients is similar to HGAS patients despite higher
perioperative mortality.
PMID- 26424681
TI - Finally, a time and place for electrophysiological testing in critically ill
patients?
PMID- 26424680
TI - Cytomegalovirus reactivation in ICU patients.
AB - INTRODUCTION: Approximately 20 years have passed since we reported our results of
histologically proven cytomegalovirus (CMV) pneumonia in non-immunocompromised
ICU patients. Even if there are more recent reports suggesting that CMV may
worsen the outcomes for ICU patients, there is no definite answer to this
question: is CMV a potential pathogen for ICU patients or is it simply a
bystander? METHODS: We will describe the pathophysiology of active CMV infection
and the most recent insights concerning the epidemiological aspects of these
reactivations. MAJOR FINDINGS: Cytomegalovirus can be pathogenic by a direct
organ insult (such as for the lung), by decreasing host defences against other
microorganisms and/or by enhancing the body's inflammatory response (as in acute
respiratory distress syndrome). The incidence of active CMV infection is
dependent on the diagnostic method used. Using the most sophisticated available
biological tools, the incidence can reach 15-20% of ICU patients (20-40% in ICU
patients with positive CMV serology). In adequately powered cohorts of patients,
active CMV infection appears to be associated with worse outcomes for
mechanically ventilated ICU patients. DISCUSSION: There is no absolute direct
proof of a negative impact of active CMV infection on the health outcomes of
mechanically ventilated patients. Prospective randomized trials are lacking.
Future trials should examine the potential benefits for health outcomes of using
antiviral treatments. Such treatments could be prophylactic, pre-emptive or used
only when there is an end-organ disease. CONCLUSION: Cytomegalovirus infection
may affect health outcomes for ICU patients. Additional prospective trials are
necessary to confirm this hypothesis.
PMID- 26424682
TI - What's new in bacterial meningitis.
PMID- 26424683
TI - Bacteremic pneumococcal pneumonia: clinical outcomes and preliminary results of
inflammatory response.
AB - PURPOSE: Further examination of clinical outcomes and inflammatory response of
bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest
to enhance the care of patients with pneumococcal CAP. METHODS: This is a
secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to
compare the time to clinical stability (TCS), length of hospital stay (LOS), and
in-hospital mortality of hospitalized pneumococcal CAP patients with and without
bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on
outcomes, we modeled all-cause in-hospital mortality using a Poisson regression
model, and TCS and LOS using Cox proportional hazards models. Adjusted
multivariate regression models were also used to predict the probability of
occurrence of each of the study outcomes. To investigate the inflammatory
response, we measured the plasma levels of pro- and anti-inflammatory cytokines
[tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ralpha, IL-6, IL-8, IL-10],
inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B
type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10
patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and
every other day during the first 6 days of hospitalization. Functional data were
presented as median and standard error of the median (SEM); due to small number
of samples no statistical comparisons were performed between groups. RESULTS:
From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic.
Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard
ratio (AHR) of 0.82 (95 % CI 0.69-0.97; p = 0.02) and had higher in-hospital
mortality with an AHR of 1.63 (95 % CI 1.06-2.50, p = 0.026). Bacteremic
pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP
(p < 0.003). Higher plasma levels of CRP, PCT, and BNP were found in bacteremic
than in non-bacteremic patients. The bacteremic group had consistently higher
plasma levels of both pro- and anti-inflammatory cytokines. The blood neutrophil
functional responses were similar in both groups of patients. CONCLUSIONS:
Bacteremic pneumococcal CAP patients were significantly associated with higher in
hospital mortality, lower TCS, and longer LOS. HIV-infected patients showed a
greater mortality which was not statistically significant. Bacteremic
pneumococcal CAP patients had higher levels of biomarkers and systemic cytokines.
PMID- 26424684
TI - Corynebacterium diphtheriae in a free-roaming red fox: case report and historical
review on diphtheria in animals.
AB - OBJECTIVES: Corynebacterium diphtheriae, the classical causative agent of
diphtheria, is considered to be nearly restricted to humans. Here we report the
first finding of a non-toxigenic C. diphtheriae biovar belfanti strain in a free
roaming wild animal. METHODS: The strain obtained from the subcutis and mammary
gland of a dead red fox (Vulpes vulpes) was characterized by biochemical and
molecular methods including MALDI-TOF and Multi Locus Sequence Typing. Since C.
diphtheriae infections of animals, usually with close contact to humans, are
reported only very rarely, an intense review comprising also scientific
literature from the beginning of the 20th century was performed. RESULTS: Besides
the present case, only 11 previously reported C. diphtheriae animal infections
could be verified using current scientific criteria. CONCLUSIONS: Our report is
the first on the isolation of C. diphtheriae from a wildlife animal without any
previous human contact. In contrast, the very few unambiguous publications on C.
diphtheriae in animals referred to livestock or pet animals with close human
contact. C. diphtheriae carriage in animals has to be considered as an
exceptionally rare event.
PMID- 26424685
TI - The Effects of Diesel Exhaust Pollution on Floral Volatiles and the Consequences
for Honey Bee Olfaction.
AB - There is growing evidence of a substantial decline in pollinators within Europe
and North America, most likely caused by multiple factors such as diseases, poor
nutrition, habitat loss, insecticides, and environmental pollution. Diesel
exhaust could be a contributing factor to this decline, since we found that
diesel exhaust rapidly degrades floral volatiles, which honey bees require for
flower recognition. In this study, we exposed eight of the most common floral
volatiles to diesel exhaust in order to investigate whether it can affect
volatile mediated plant-pollinator interaction. Exposure to diesel exhaust
altered the blend of common flower volatiles significantly: myrcene was
considerably reduced, beta-ocimene became undetectable, and beta-caryophyllene
was transformed into its cis-isomer isocaryophyllene. Proboscis extension
response (PER) assays showed that the alterations of the blend reduced the
ability of honey bees to recognize it. The chemically reactive nitrogen oxides
fraction of diesel exhaust gas was identified as capable of causing degradation
of floral volatiles.
PMID- 26424686
TI - The importance of tailoring physicians' trauma care training needs in rural
environments.
AB - SUMMARY: Gaps in the provision of care exist in the initial evaluation and
management of patients first cared for in the most rural settings. We designed a
survey to explore what unmet educational needs might exist so as to improve the
care of patients before transfer. Here we discuss opportunities for tailored
training that will enhance learning capacity, narrow the trauma education gap and
improve trauma care, particularly in rural environments.
PMID- 26424687
TI - Providing mentorship support to general surgery residents: a model for structured
group facilitation.
AB - SUMMARY: Mentorship is foundational to surgical training, with recognized
benefits for both mentees and mentors. The University of Ottawa General Surgery
Mentorship Program was developed as a module-based group facilitation program to
support inclusive personal and professional development of junior general surgery
residents. The group format provided an opportunity for both vertical and
horizontal mentorship relationships between staff mentors and resident mentees.
Perceived benefits of program participants were evaluated at the conclusion of
the first year of the program. The program was well-received by staff and
resident participants and may provide a time-efficient and inclusive mentorship
structure with the additional benefit of peer support. We review the development
and implementation of the program to date and share our mentorship experience to
encourage the growth of formal mentorship opportunities within general surgery
training programs.
PMID- 26424688
TI - Current perioperative practice in Canadian vascular surgery.
AB - BACKGROUND: The Enhanced Recovery After Surgery (ERAS) Society has set out to
improve patient recovery by developing evidence-based perioperative practices.
Many institutions and other specialties have begun to apply their principles with
great success; however, ERAS principles focus mostly on general surgery, and
their applicability to other specialties, such as vascular surgery, is less
clear. We sought to investigate the current standard of perioperative care in
Canadian vascular surgery by assessing surgeons' perceptions of evidence
supporting ERAS practices, identifying barriers to aligning them and identifying
aspects of perioperative care that require research specific to vascular surgery
before they could be broadly applied. METHODS: We administered an online survey
with 26 questions to all Canadian Society for Vascular Surgery members. RESULTS:
Respondents varied largely in perioperative practice, most notably in the use of
nasogastric tubes, Foley catheters and neck drains. Familiarity with supporting
evidence was poor. Approximately half (44%) of respondents were not familiar with
contrary evidence, while those who were often perceived institutional barriers to
change. Finally, one-third (30%) of respondents felt that relevant evidence did
not exist to support changing their practice. CONCLUSION: The variability of
perioperative practice in Canadian vascular surgery is likely due to multiple
factors, including a lack of specific evidence. Further research in areas of
perioperative vascular care where the current standard of practice varies most
greatly may help improve recovery after vascular surgery in Canada over simply
adopting existing ERAS principles.
PMID- 26424689
TI - Trends in the Canadian Surgery Forum (CSF): analysis of the CSF program over the
past decade.
AB - SUMMARY: Numerous clinical and basic science-related innovations have been
presented at the Canadian Surgery Forum (CSF). We sought to define changes in
both the content and methodology of the CSF scientific program over the past
decade. While the total volume of CSF abstract presentations has increased
dramatically, the methodological quality has remained static, with few randomized
trials and minimal prospective work. Although the majority of the scientific
content is associated with urban university centres, the program also encourages
content from community practices. Surgical education, hepatopancreatobiliary and
bariatric content have increased substantially, but remain secondary to
colorectal diseases.
PMID- 26424690
TI - Significance of CD4+ T-cell count in the management of appendicitis in patients
with HIV.
AB - SUMMARY: Identification of complicated appendicitis (CA) is critical to the
management of appendicitis. However, previous studies have not investigated
indicators of CA among patients with HIV or whether it is safe to use
conservative treatment for appendicitis in these patients. Among 322 patients
with appendicitis, we identified 14 who had HIV. Six of them were operated and 8
were treated with antibiotics; CA was diagnosed in 4. Patients with HIV and CA
had a significantly lower CD4+ T-cell count than those with uncomplicated
appendicitis. A white blood cell count lower than 7.4 * 10(9)/L was observed
exclusively in patients with CA. No patient with HIV whose appendicitis was
treated conservatively died or experienced a recurrence. We discuss our findings,
which suggest the possibility of conservative treatment of appendicitis in
patients with HIV and identification of CA by low CD4+ T-cell count.
PMID- 26424691
TI - Proceedings of the 2015 MidSouth Computational Biology and Bioinformatics Society
(MCBIOS) Conference.
PMID- 26424694
TI - VI International Congress of Histology and Tissue Engineering - XVIII Congress of
the Spanish Society of Histology and Tissue Engineering - II Iberoamerican
Congress of Histology. 16-18 September, 2015, Bilbao, Spain.
PMID- 26424692
TI - Risk factors for outcome in refractory acute myeloid leukemia patients treated
with a combination of fludarabine, cytarabine, and amsacrine followed by a
reduced-intensity conditioning and allogeneic stem cell transplantation.
AB - INTRODUCTION: Hematopoietic stem cell transplantation (HCT) is considered a
standard treatment for high-risk acute myeloid leukemia (AML) in first or second
complete remission (CR). Unfortunately, not all patients achieve complete
remission prior to HCT. We sought to establish predictive factors for survival
after HCT for refractory AML after FLAMSA-RIC. PATIENTS AND METHODS: We analyzed
the outcome of 44 consecutive patients aged between 21 and 65 years transplanted
at the University Hospitals of Jena and Leipzig for refractory AML between 2006
and January 2013. Conditioning for HCT was performed with chemotherapy consisting
of fludarabine, cytarabine, and amsacrine followed by total body irradiation or
busulfan combined with cyclophosphamide. Antithymocyte globulin was given when
transplanting from unrelated donors (FLAMSA-RIC). RESULTS: Estimated overall
survival (OS) and event-free survival (EFS) at 3 years after a median follow-up
of 34 (range 6-71) months were 15 and 12 %, respectively. Causes of death were
relapse in 66 %, infection in 11 %, and graft-versus-host disease (GvHD) in 7 %
of all patients. Twenty-five from 42 evaluable patients (60 %) achieved CR 4
weeks after HCT, while eight patients had partial remission (PR), and nine
patients had stable disease (SD). Another six patients with PR and SD achieved CR
(overall CR rate 74 %) from 4 weeks to day 90 after HCT following reduction in
immunosuppression. The strongest favorable factors in univariate analysis for OS,
EFS, and RI were >=98 % total donor chimerism 2-4 weeks after HCT and <3 lines of
pretreatment prior to HCT. In addition, better OS was detected in patients with
<20 % bone marrow blasts alone (32 vs. 5 % at 3 years) and in combination with <3
lines of pretreatment (38 vs. 4 % at 3 years). Only a trend for better EFS and
lower RI was observed in patients with limited chronic GvHD. In addition, a lower
RI was seen in patients with <5 % blasts 4 weeks after HCT. Multivariate analysis
revealed that >=98 % donor chimerism 2-4 weeks after HCT for OS, EFS, and RI and
<3 lines of pretreatment for OS and EFS are the strongest predictors for better
outcome. CONCLUSION: FLAMSA-RIC shows long-term survival in refractory AML
patients. Factors for favorable outcome are <20 % bone marrow blasts prior to
HCT, <3 lines of pretreatment and complete donor chimerism after HCT.
PMID- 26424693
TI - Comparison of nine prognostic scores in patients with brain metastases of breast
cancer receiving radiotherapy of the brain.
AB - PURPOSE: Several prognostic indices (PI) have been developed to stratify patients
with brain metastases in groups with good or bad prognosis. The aim of our study
was to compare nine prognostic scores for patients with brain metastases (BM) of
breast cancer receiving radiotherapy. METHODS: The clinical data of 139 breast
cancer patients with BM were collected retrospectively. All patients were treated
with cerebral radiotherapy or surgery followed by radiotherapy between January
2007 and December 2012. The prognostic value and accuracy of recursive
partitioning analysis (RPA), RPA II, graded prognostic assessment (GPA), basic
score for BM, Breast-RPA, Breast-GPA, Rades Score 2011, Germany Score and Breast
Rades Score were assessed. RESULTS: The median survival after BM diagnosis in our
cohort was 14 months. The overall 6-month, 1-, 2- and 3-year survival rates were
49.6, 37.4, 20.9 and 13.7 %, respectively. Most of the PI were associated with
OS, but univariate analysis favored GPA regarding OS. GPA was the most accurate
score to identify patients with long (longer than 12 months) and Breast-GPA
patients with short (<3 months) life expectancy. CONCLUSIONS: GPA and Breast-GPA
seem to be the most useful scores and perform better than other PI for breast
cancer patients with BM receiving radiotherapy.
PMID- 26424695
TI - Hypoxia-Induced WSB1 Promotes the Metastatic Potential of Osteosarcoma Cells.
AB - Intratumoral hypoxia occurs in many solid tumors, where it is associated with the
development of metastatic character. However, the connections between these
phenomena are not fully understood. In this study, we define an integrative role
for the E3 ubiquitin ligase subunit WSB1. In primary osteosarcomas, increased
levels of WSB1 correlated with pulmonary metastatic potential. RNAi-mediated
attenuation of WSB1 or disruption of its E3 ligase activity potently suppressed
tumor metastasis. Quantitative proteomic and functional analyses revealed that
WSB1 ubiquitylates the Rho-binding protein RhoGDI2 and promotes its proteasomal
degradation, thereby activating Rac1 to stimulate tumor cell motility and
invasion. Our findings show how WSB1 regulates key steps of the metastatic
cascade in hypoxia-driven osteosarcoma, and they highlight a candidate
therapeutic target to potentially improve the survival of patients with
metastatic disease.
PMID- 26424696
TI - Fluorophore-NanoLuc BRET Reporters Enable Sensitive In Vivo Optical Imaging and
Flow Cytometry for Monitoring Tumorigenesis.
AB - Fluorescent proteins are widely used to study molecular and cellular events, yet
this traditionally relies on delivery of excitation light, which can trigger
autofluorescence, photoxicity, and photobleaching, impairing their use in vivo.
Accordingly, chemiluminescent light sources such as those generated by
luciferases have emerged, as they do not require excitation light. However,
current luciferase reporters lack the brightness needed to visualize events in
deep tissues. We report the creation of chimeric eGFP-NanoLuc (GpNLuc) and
LSSmOrange-NanoLuc (OgNLuc) fusion reporter proteins coined LumiFluors, which
combine the benefits of eGFP or LSSmOrange fluorescent proteins with the bright,
glow-type bioluminescent light generated by an enhanced small luciferase subunit
(NanoLuc) of the deep-sea shrimp Oplophorus gracilirostris. The intramolecular
bioluminescence resonance energy transfer that occurs between NanoLuc and the
fused fluorophore generates the brightest bioluminescent signal known to date,
including improved intensity, sensitivity, and durable spectral properties,
thereby dramatically reducing image acquisition times and permitting highly
sensitive in vivo imaging. Notably, the self-illuminating and bifunctional nature
of these LumiFluor reporters enables greatly improved spatiotemporal monitoring
of very small numbers of tumor cells via in vivo optical imaging and also allows
the isolation and analyses of single cells by flow cytometry. Thus, LumiFluor
reporters are inexpensive, robust, noninvasive tools that allow for markedly
improved in vivo optical imaging of tumorigenic processes.
PMID- 26424697
TI - Sublethal vancomycin-induced ROS mediating antibiotic resistance in
Staphylococcus aureus.
AB - Staphylococcus aureus is the leading cause of many human infectious diseases.
Besides infectious dangers, S. aureus is well-known for the quickly developed
drug resistance. Although great efforts have been made, mechanisms underlying the
antibiotic effects of S. aureus are still not well clarified. Recently, reports
have shown that oxidative stress connects with bactericidal antibiotics [Dwyer et
al. (2009) Curr. Opin. Microbiol. 12: , 482-489]. Based on this point, we
demonstrate that reactive oxygen species (ROS) induced by sublethal vancomycin
may be partly responsible for the antibiotic resistance in heterogeneous
vancomycin resistant S. aureus (hVRSA). Sublethal vancomycin treatment may induce
protective ROS productions in hVRSA, whereas reduction in ROS level in hVRSA
strains may increase their vancomycin susceptibility. Moreover, low dose of ROS
in VSSA (vancomycin susceptible S. aureus) strains may promote their survival
under vancomycin conditions. Our findings reveal that modest ROS generation may
be protective for vancomycin resistance in hVRSA. These results recover novel
insights into the relationship between oxidative stress and bacterial resistance,
which has important applications for further use of antibiotics and development
of therapeutics strategies for hVRSA.
PMID- 26424698
TI - Chronic aerobic swimming exercise promotes functional and morphological changes
in rat ileum.
AB - Several studies have reported the gastrointestinal (GI) effects promoted by the
physical exercise. Thus, we aimed to evaluate the influence of swimming exercise
on the contractile reactivity, lipid peroxidation and morphology of rat ileum.
Wistar rats were divided into sedentary (SED) and groups exercised for two (EX2),
four (EX4), six (EX6) or eight (EX8) weeks, 5 days/week. Animals were killed; the
ileum was removed and suspended in organ baths where the isotonic contractions
were recorded. Lipid peroxidation was evaluated by MDA (malondialdehyde)
measurement with TBARS (thiobarbituric acid reactive substances) assay and
morphology by histological staining. Cumulative concentration-response curves to
KCl were attenuated, as the Emax values were changed from 100% (SED) to 63.1+/
3.9 (EX2), 48.8+/-3.8 (EX4), 19.4+/-1.8 (EX6) and 59.4+/-2.8% (EX8). Similarly,
cumulative concentration-response curves to carbamylcholine hydrochloride (CCh)
were attenuated, as the Emax values were changed from 100% (SED) to 74.1+/-5.4
(EX2), 75.9+/-5.2 (EX4) and 62.9+/-4.6 (EX6), but not in the EX8 (89.7+/-3.4%).
However, CCh potency was increased in this latter, as the EC50 was altered from
1.0+/-0.1*10(-6) (SED) to 2.1+/-0.4*10(-7) (EX8). MDA concentration was altered
only in EX4 (44.3+/-4.4) compared with SED (20.6+/-3.6 MUmol/l). Circular layer
was reduced in SED when compared with the exercised groups. Conversely,
longitudinal layer was increased. In conclusion, chronic swimming exercise
reduces the ileum contraction, equilibrates the oxidative damage and promotes
changes in tissue size to establish an adaptation to the exercise.
PMID- 26424699
TI - Impact of working 48 h per week on opportunities for training and patient
contact: the experience of Irish interns.
AB - OBJECTIVE: The European Working Time Regulations (EWTR) have been criticized for
its purported negative impact on the training of junior doctors. The aim of this
study was to examine the amount of time interns spent engaging in various work
activities. DESIGN: An online time-use diary was used to collect data from
interns. SETTING: Two teaching hospitals in the Republic of Ireland.
PARTICIPANTS: A total of 45 interns logged at least one 24-h period. The logs
were obtained from 67 shifts from a surgical rotation and 83 shifts from a
medical rotation. MAIN OUTCOME MEASURES: The amount of time interns spent
engaging in direct patient care, indirect patient care, educational activities
and personal activities. RESULTS: On day shift, medical interns spent a
significantly smaller proportion of the shift on direct care (159/613 min, 25.9%
versus 214/636 min, 33.6%) and a greater proportion on education (195/613 min,
31.8% versus 139/636 min, 21.9%) than surgical interns. On extended days, medical
interns spent a significantly larger proportion of the shift on education than
surgical interns (243/814 min, 29.9% versus 126/804, 15.7% min). On night shift,
medical interns spent a significantly greater proportion of the shift on direct
care (590/720 min, 81.9% versus 346/727 min, 47.6%) and education (33/720 min,
4.6% versus 6/727 min, 0.8%) than surgical interns. CONCLUSIONS: The interns in
the study reported spending more time on direct patient care and educational
activities, and less time on indirect patient care activities than interns in
other countries.
PMID- 26424700
TI - Is accreditation linked to hospital infection rates? A 4-year, data linkage study
of Staphylococcus aureus rates and accreditation scores in 77 Australian acute
hospitals.
AB - OBJECTIVES: To test our hypothesis that hospitals with higher accreditation
scores, specifically in infection control, would be associated with lower
Staphylococcus aureus bacteraemia (SAB) rates. DESIGN: A retrospective cohort
study. SETTING AND PARTICIPANTS: Acute public hospitals (n = 77) in New South
Wales, Australia, with reported SAB rates, results from two accreditation surveys
and results from at least four hand hygiene audits. METHODS: We linked three
separate data sets comprising SAB rates, accreditation scores and hand hygiene
rates. SAB rates were regressed against accreditation scores, hand hygiene audit
rates and hospital demographics using a generalized linear model to account for
the non-linear nature of our outcome variable. RESULTS: Significant (P < 0.05)
findings included the following: SAB rates across all hospitals fell from 1.34
per 10 000 bed days in 2009 to 0.77 per 10 000 bed days in 2012; mean SAB rates
in small hospitals (0.62/10 000 bed days) over the study period were lower than
those for principal referral hospitals (1.52/10 000 bed days); smaller hospitals
with higher accreditation scores had lower SAB rates, but larger hospitals with
higher overall accreditation scores had higher SAB rates, although the effect
size was small (<2%). CONCLUSIONS: There is a strong evidence base for using SAB
rates to measure the impact of infection control programs that are assessed
during accreditation. However, there is less evidence to support whether
accreditation scores accurately reflect implementation of the infection control
accreditation standards. This impacts identification of indicators to measure
patient safety and quality of care, especially in ensuring these are appropriate
across a range of hospital size and activities.
PMID- 26424701
TI - Bradycardia as an early warning sign for cardiac arrest during routine
laparoscopic surgery.
AB - OBJECTIVES: The aim of this study was to identify clinical patterns of
occurrence, management and outcomes surrounding cardiac arrest during
laparoscopic surgery using the Australian Incident Monitoring Study (AIMS)
database to guide possible prevention and treatment. SETTING: The AIMS database
includes incident reports from participating clinicians from secondary and
tertiary healthcare centres across Australia and New Zealand. PARTICIPANTS: The
AIMS database holds over 11 000 peri- and intraoperative incidents. PRIMARY AND
SECONDARY OUTCOME MEASURES: The primary outcome was to characterize the pattern
of events surrounding cardiac arrest. The secondary outcome was to identify
successful management strategies in the possible prevention and treatment of
cardiac arrest during laparoscopic surgery. RESULTS: Fourteen cases of cardiac
arrest during laparoscopic surgery were identified. The majority of cases
occurred in 'fit and healthy' patients during elective gynaecological and general
surgical procedures. Twelve cases of cardiac arrest were directly associated with
pneumoperitoneum with bradycardia preceding cardiac arrest in 75% of these.
Management included deflation of pneumoperitoneum, atropine administration and
cardiopulmonary resuscitation with circulatory restoration in all cases. The
results imply vagal mechanisms associated with peritoneal distension as the
predominant contributor to bradycardia and subsequent cardiac arrest during
laparoscopy. CONCLUSIONS: Bradycardia during gas insufflation is not necessarily
a benign event and appears to be a critical early warning sign for possible
impending and unexpected cardiac arrest. Immediate deflation of pneumoperitoneum
and atropine administration are effective measures that may alleviate bradycardia
and possibly avert progression to cardiac arrest.
PMID- 26424702
TI - The missing evidence: a systematic review of patients' experiences of adverse
events in health care.
AB - PURPOSE: Preventable patient harm due to adverse events (AEs) is a significant
health problem today facing contemporary health care. Knowledge of patients'
experiences of AEs is critical to improving health care safety and quality. A
systematic review of studies of patients' experiences of AEs was conducted to
report their experiences, knowledge gaps and any challenges encountered when
capturing patient experience data. DATA SOURCES: Key words, synonyms and subject
headings were used to search eight electronic databases from January 2000 to
February 2015, in addition to hand-searching of reference lists and relevant
journals. STUDY SELECTION: Titles and abstracts of publications were screened by
two reviewers and checked by a third. Full-text articles were screened against
the eligibility criteria. DATA EXTRACTION: Data on design, methods and key
findings were extracted and collated. RESULTS: Thirty-three publications
demonstrated patients identifying a range of problems in their care; most
commonly identified were medication errors, communication and coordination of
care problems. Patients' income, education, health burden and marital status
influence likelihood of reporting. Patients report distress after an AE, often
exacerbated by receiving inadequate information about the cause. Investigating
patients' experiences is hampered by the lack of large representative patient
samples, data over sufficient time periods and varying definitions of an AE.
CONCLUSION: Despite the emergence of policy initiatives to enhance patient
engagement, few studies report patients' experiences of AEs. This information
must be routinely captured and utilized to develop effective, patient-centred and
system-wide policies to minimize and manage AEs.
PMID- 26424704
TI - Analysis of the Information Quality of Bariatric Surgery Smartphone Applications
Using the Silberg Scale.
AB - There is a paucity of literature that has evaluated the information quality of
the current bariatric and obesity applications. Our objective was to evaluate the
quality of currently available smartphone applications for bariatric-patient care
using the Silberg scale. The two most widely used smartphone application online
stores were searched in June 2014 and a total of 39 applications were evaluated.
The average Silberg score of the 39 applications was 4.0 +/- 1.76. The current
gaps of information quality include the lack of provision of appropriate
references, full disclosure of sponsorship, and accurate disclosure whether the
application has been modified in the past month.
PMID- 26424703
TI - Response of lactate metabolism in brain glucosensing areas of rainbow trout
(Oncorhynchus mykiss) to changes in glucose levels.
AB - There is no evidence in fish brain demonstrating the existence of changes in
lactate metabolism in response to alterations in glucose levels. We induced in
rainbow trout through intraperitoneal (IP) treatments, hypoglycaemic or
hyperglycaemic changes to assess the response of parameters involved in lactate
metabolism in glucosensing areas like hypothalamus and hindbrain. To distinguish
those effects from those induced by peripheral changes in the levels of
metabolites or hormones, we also carried out intracerebroventricular (ICV)
treatments with 2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analogue
thus inducing local glucopenia) or glucose. Finally, we also incubated
hypothalamus and hindbrain in vitro in the presence of increased glucose
concentrations. The changes in glucose availability were in general correlated to
changes in the amount of lactate in both areas. However, when we assessed in
these areas the response of parameters related to lactate metabolism, the results
obtained were contradictory. The increase in glucose levels did not produce in
general the expected changes in those pathways with only a minor increase in
their capacity of lactate production. The decrease in glucose levels was,
however, more clearly related to a decreased capacity of the pathways involved in
the production and use of lactate, and this was especially evident after ICV
treatment with 2-DG in both areas. In conclusion, the present results while
addressing the existence of changes in lactate metabolism after inducing changes
in glucose levels in brain glucosensing areas only partially support the possible
existence of an astrocyte-neuron lactate shuttle in hypothalamus and hindbrain of
rainbow trout relating glucose availability to lactate production and use.
PMID- 26424705
TI - Increased Prevalence of Irritable Bowel Syndrome in a Cohort of French Morbidly
Obese Patients Candidate for Bariatric Surgery.
AB - BACKGROUND: Only a few recent reports have suggested a correlation between
obesity and irritable bowel syndrome (IBS). We aimed to determine the prevalence
and severity of IBS in a prospective cohort of obese patients undergoing
bariatric surgery in Nice Hospital (France). METHODS: One hundred obese patients
were included prospectively before bariatric surgery. A diagnosis of IBS and each
subtype was performed according to Rome-III criteria using a Bristol scale for
stool consistency. Patients provided information on IBS-related comorbidities,
including chronic fatigue, migraine, lower back pain, gastroesophageal reflux
disease (GERD), genitourinary problems, and dyspepsia. Patients completed
questionnaires to assess the severity of IBS, GERD, psychological factors
(anxiety, depression), fatigue, and quality of life. RESULTS: Thirty patients
fulfilled the Rome-III criteria for IBS. There was no difference in age, gender,
or BMI between obese patients with or without IBS. Obese patients with IBS
reported a significantly higher prevalence of GERD, migraines, lower back pain,
genitourinary problems, chronic fatigue, and dyspepsia. Obese patients with IBS
had significant higher scores of fatigue, anxiety, depression, and poorer quality
of life. Obese patients that had both IBS and GERD had significantly higher IBS
severity scores than those without GERD. In a logistic regression model including
BMI, anxiety, depression, gender, and GERD score, only anxiety was significantly
and independently associated with IBS. CONCLUSIONS: Thirty percent of obese
patients had IBS: its severity was not correlated with BMI. However, anxiety was
independently associated with IBS, suggesting that psychological factors are key
features of IBS, whatever the presence of obesity.
PMID- 26424706
TI - A Comment on "Obesity Surgery and Ramadan: a Prospective Analysis of Nutritional
Intake, Hunger and Satiety and Adaptive Behaviours During Fasting".
PMID- 26424707
TI - Economic costs of outbreaks of acute viral gastroenteritis due to norovirus in
Catalonia (Spain), 2010-2011.
AB - BACKGROUND: To determine the direct and indirect costs of outbreaks of acute
viral gastroenteritis (AVG) due to norovirus in closed institutions (hospitals,
social health centers or nursing homes) and the community in Catalonia in 2010
11. METHODS: Information on outbreaks were gathered from the reports made by
epidemiological surveillance units. Direct costs (medical visits, hospital stays,
drug treatment, sample processing, transport, diagnostic tests, monitoring and
control of the outbreaks investigated) and indirect costs (lost productivity due
to work absenteeism, caregivers time and working hours lost due to medical
visits) were calculated. RESULTS: Twenty-seven outbreaks affecting 816 people in
closed institutions and 74 outbreaks affecting 1,940 people in the community were
detected. The direct and indirect costs of outbreaks were ? 131,997.36 (?
4,888.79 per outbreak) in closed institutions and ? 260,557.16 (? 3,521.04 per
outbreak) in community outbreaks. The cost per case was ? 161.76 in outbreaks in
closed institutions and ? 134.31 in community outbreaks. The main costs were
surveillance unit monitoring (? 116,652.93), laboratory diagnoses (? 119,950.95),
transport of samples (? 69,970.90), medical visits (? 25,250.50) and
hospitalization (? 13,400.00). CONCLUSIONS: The cost of outbreaks of acute viral
gastroenteritis due to norovirus obtained in this study was influenced by the
number of people affected and the severity of the outbreak, which determined
hospitalizations and work absenteeism. Urgent reporting of outbreaks would allow
the implementation of control measures that could reduce the numbers affected and
the duration of the illness and thus the costs derived from them.
PMID- 26424708
TI - Preoperative neutrophil/lymphocyte ratio and prognostic nutritional index predict
survival in patients with non-small cell lung cancer.
AB - BACKGROUND: The immunological status, consisting of "inflammation status" and
"nutritional condition," is important for the survival of patients with various
cancers, including non-small cell lung cancer (NSCLC). The neutrophil/lymphocyte
ratio (NLR) reflects the inflammation status, and the prognostic nutritional
index (PNI) reflects the immunological nutritional condition. In the present
study, the correlation between the NLR and the PNI as well as the consistency and
magnitude of the prognostic impact of the NLR and the PNI were investigated.
METHODS: We conducted a retrospective review of data from 334 patients who had
undergone a curative resection for NSCLC. The NLR and the PNI were calculated,
which was routinely performed before surgery. The correlations between the NLR
and the PNI and survival were then evaluated. RESULTS: A clear inverse
correlation was observed between the NLR and the PNI. The NLR was associated with
sex, smoking history, the CEA level, tumor size, and vascular invasion. The PNI
was associated with sex, age, smoking history, tumor size, histological type,
tumor differentiation, and vascular invasion. Patients with NLR >=2.5 had a
significantly poorer survival outcome, and patients with PNI <50 had a
significantly poorer survival outcome. A multivariate analysis demonstrated that
age, nodal metastasis, tumor differentiation, NLR, and PNI were independent
predictors of disease-free and overall survival. CONCLUSIONS: Our study
demonstrated a significant inverse correlation between the NLR and the PNI, and a
high NLR and a low PNI were significantly associated with a poor survival among
patients who had undergone a complete resection for NSCLC.
PMID- 26424709
TI - The Relationship Between Distance and Post-operative Visit Attendance Following
Medical Male Circumcision in Nyanza Province, Kenya.
AB - To date, there is no research on voluntary medical male circumcision (VMMC)
catchment areas or the relationship between distance to a VMMC facility and
attendance at a post-operative follow-up visit. We analyzed data from a randomly
selected subset of males self-seeking circumcision at one of 16 participating
facilities in Nyanza Province, Kenya between 2008 and 2010. Among 1437
participants, 46.7 % attended follow-up. The median distance from residence to
utilized facility was 2.98 km (IQR 1.31-5.38). Nearly all participants (98.8 %)
lived within 5 km from a facility, however, 26.3 % visited a facility more than 5
km away. Stratified results demonstrated that among those utilizing fixed
facilities, greater distance was associated with higher odds of follow-up non
attendance (OR5.01-10km vs. 0-1km = 1.71, 95 % CI 1.08, 2.70, p = 0.02; OR>10km
vs. 0-1 km = 2.80, 95 % CI 1.26, 6.21, p = 0.01), adjusting for age and district
of residence. We found 5 km marked the threshold distance beyond which follow-up
attendance significantly dropped. These results demonstrate distance is an
important predictor of attending follow-up, and this relationship appears to be
modified by facility type.
PMID- 26424710
TI - Symbiosis dependent accumulation of primary metabolites in arbuscule-containing
cells.
AB - BACKGROUND: The arbuscular mycorrhizal symbiosis is characterized by the presence
of different symbiotic structures and stages within a root system. Therefore
tools allowing the analysis of molecular changes at a cellular level are required
to reveal insight into arbuscular mycorrhizal (AM) symbiosis development and
functioning. RESULTS: Here we describe the analysis of metabolite pools in
arbuscule-containing cells, which are the site of nutrient transfer between AM
fungus and host plant. Laser capture microdissection (LCM) combined with gas
chromatography mass spectrometry (GC-EI/TOF-MS) enabled the analysis of primary
metabolite levels,which might be of plant or fungal origin, within these cells.
CONCLUSIONS: High levels of the amino acids, aspartate, asparagine, glutamate,
and glutamine, were observed in arbuscule-containing cells. Elevated amounts of
sucrose and the steady-state of hexose levels indicated a direct assimilation of
monosaccharides by the fungal partner.
PMID- 26424711
TI - Incompatibility of busulfan with 1 ml Luer-Lock syringes.
PMID- 26424712
TI - Respondent-driven sampling as a recruitment method for men who have sex with men
in southern sub-Saharan Africa: a cross-sectional analysis by wave.
AB - OBJECTIVES: Respondent-driven sampling (RDS) is a popular method for recruiting
men who have sex with men (MSM). Our objective is to describe the ability of RDS
to reach MSM for HIV testing in three southern African nations. METHODS: Data
collected via RDS among MSM in Lesotho (N=318), Swaziland (N=310) and Malawi
(N=334) were analysed by wave in order to characterise differences in sample
characteristics. Seeds were recruited from MSM-affiliated community-based
organisations. Men were interviewed during a single study visit and tested for
HIV. chi(2) tests for trend were used to examine differences in the proportions
across wave category. RESULTS: A maximum of 13-19 recruitment waves were achieved
in each study site. The percentage of those who identified as gay/homosexual
decreased as waves increased in Lesotho (49% to 27%, p<0.01). In Swaziland and
Lesotho, knowledge that anal sex was the riskiest type of sex for HIV
transmission decreased across waves (39% to 23%, p<0.05, and 37% to 19%, p<0.05).
The percentage of participants who had ever received more than one HIV test
decreased across waves in Malawi (31% to 12%, p<0.01). In Lesotho and Malawi, the
prevalence of testing positive for HIV decreased across waves (48% to 15%, p<0.01
and 23% to 11%, p<0.05). Among those living with HIV, the proportion of those
unaware of their status increased across waves in all study sites although this
finding was not statistically significant. CONCLUSIONS: RDS that extends deeper
into recruitment waves may be a promising method of reaching MSM with varying
levels of HIV prevention needs.
PMID- 26424714
TI - No reduction in fibreoptic intubation rates with universal video laryngoscopy.
PMID- 26424713
TI - Sexually transmitted infections associated with alcohol use and HIV infection
among men who have sex with men in Kampala, Uganda.
AB - OBJECTIVES: Few studies have been conducted in Africa to assess prevalence of
sexually transmitted infections (STIs) and risk factors among men who have sex
with men (MSM). We report findings from the first behavioural survey to include
STI testing among MSM in Kampala, Uganda. METHODS: Respondent-driven sampling
(RDS) was used to recruit MSM for a biobehavioural survey. Eligible participants
were men who reported anal sex with another man in the previous 3 months, were 18
years or older, and resided in Kampala. Information was collected on
demographics, sexual behaviour, alcohol and drug use, and STI symptoms. Blood,
urine and rectal specimens were tested for syphilis, HIV, rectal and urethral
gonorrhoea, and chlamydia. Analyses weighted for RDS were conducted to assess
associations with STI diagnosis. RESULTS: A total of 295 MSM participated in the
survey. Almost half (weighted percentage: 47.3%) reported STI symptoms in the
last 6 months and 12.9% tested HIV-positive. Prevalence of non-HIV STI was 13.5%;
syphilis prevalence was 9.0%. Adjusting for age and education, STI was associated
with HIV (adjusted OR (AOR)=3.46, 95% CI 1.03 to 11.64), alcohol use before sex
(AOR=4.99, 95% CI 1.86 to 13.38) and having sold sex in the last 3 months
(AOR=3.17, 95% CI 1.25 to 8.07), and inversely associated with having anonymous
sex partners (AOR=0.20, 95% CI 0.07 to 0.61). CONCLUSIONS: We observed high
levels of self-reported STI symptoms and STI prevalence associated with alcohol
use and HIV among MSM in Kampala. Public health interventions supporting MSM are
needed to address STI risk and facilitate access to diagnosis and treatment
services.
PMID- 26424715
TI - In reply: No reduction in fibreoptic intubation rates with universal video
laryngoscopy.
PMID- 26424717
TI - Intraoperative protective ventilation: too early to redefine management
parameters?
PMID- 26424718
TI - Permission fees for reproducing tables in journal articles are exorbitant.
PMID- 26424716
TI - The Emergence of 2-Oxoglutarate as a Master Regulator Metabolite.
AB - The metabolite 2-oxoglutarate (also known as alpha-ketoglutarate, 2-ketoglutaric
acid, or oxoglutaric acid) lies at the intersection between the carbon and
nitrogen metabolic pathways. This compound is a key intermediate of one of the
most fundamental biochemical pathways in carbon metabolism, the tricarboxylic
acid (TCA) cycle. In addition, 2-oxoglutarate also acts as the major carbon
skeleton for nitrogen-assimilatory reactions. Experimental data support the
conclusion that intracellular levels of 2-oxoglutarate fluctuate according to
nitrogen and carbon availability. This review summarizes how nature has
capitalized on the ability of 2-oxoglutarate to reflect cellular nutritional
status through evolution of a variety of 2-oxoglutarate-sensing regulatory
proteins. The number of metabolic pathways known to be regulated by 2
oxoglutarate levels has increased significantly in recent years. The signaling
properties of 2-oxoglutarate are highlighted by the fact that this metabolite
regulates the synthesis of the well-established master signaling molecule, cyclic
AMP (cAMP), in Escherichia coli.
PMID- 26424719
TI - In Vitro and In Vivo Comparison of Selected Ga-68 and Zr-89 Labelled
Siderophores.
AB - PURPOSE: Some [(68)Ga]siderophores show promise in specific and sensitive imaging
of infection. Here, we compare the in vitro and in vivo behaviour of selected Ga
68 and Zr-89 labelled siderophores. PROCEDURES: Radiolabelling was performed in
HEPES or sodium acetate buffer systems. Radiochemical purity of labelled
siderophores was determined using chromatography. Partition coefficients, in
vitro stability and protein binding affinities were determined. Ex vivo
biodistribution and animal imaging was studied in mice. RESULTS: Certain
differences among studied siderophores were observed in labelling efficiency.
Protein binding and stability tests showed highest stabilities and lowest protein
binding affinities for Ga-68 and [(89)Zr]triacetylfusarinine C (TAFC). All
studied Ga-68 and [(89)Zr]siderophores exhibited a similar biodistribution and
pharmacokinetics in mice with the exception of [(89)Zr]ferrioxamine E (FOXE).
CONCLUSIONS: Zr-89 and [(68)Ga]siderophores showed analogous in vitro and in vivo
behaviour. Tested [(89)Zr]siderophores could be applied for longitudinal positron
emission tomography (PET) studies of fungal infections and especially TAFC for
the development of novel bioconjugates.
PMID- 26424721
TI - Implementation and Use of State-of-the-Art, Cell-Based In Vitro Assays.
AB - The impressive advances in the generation and interpretation of functional omics
data have greatly contributed to a better understanding of the (patho-)physiology
of many biological systems and led to a massive increase in the number of
specific targets and phenotypes to investigate in both basic and applied
research. The obvious complexity revealed by these studies represents a major
challenge to the research community and asks for improved target characterisation
strategies with the help of reliable, high-quality assays. Thus, the use of
living cells has become an integral part of many research activities because the
cellular context more closely represents target-specific interrelations and
activity patterns. Although still predominant, the use of traditional two
dimensional (2D) monolayer cell culture models has been gradually complemented by
studies based on three-dimensional (3D) spheroid (Sutherland 1988) and other 3D
tissue culture systems (Santos et al. 2012; Matsusaki et al. 2014) in an attempt
to employ model systems more closely representing the microenvironment of cells
in the body. Hence, quite a variety of state-of-the-art cell culture models are
available for the generation of novel chemical probes or the identification of
starting points for drug development in translational research and pharma drug
discovery. In order to cope with these information-rich formats and their
increasing technical complexity, cell-based assay development has become a
scientific research topic in its own right and is used to ensure the provision of
significant, reliable and high-quality data outlasting any discussions related to
the current "irreproducibility epidemic" (Dolgin 2014; Prinz et al. 2011; Schatz
2014). At the same time the use of cells in microplate assay formats has become
state of the art and greatly facilitates rigorous cell-based assay development by
providing the researcher with the opportunity to address the multitude of factors
affecting the actual assay results in a systematic fashion and a timely manner.
This microplate-based assay development strategy should result in the setting up
of more robust and reliable test systems that ensure and increase the confidence
in the statistical significance of the actual data generated. And, although assay
miniaturisation is essential in order to achieve this, most, if not all, cell
based assays can be easily reformatted and adapted to be used in this format in a
straightforward manner. This synopsis aims at summarising valuable, general
observations made when implementing a diverse set of functional cellular in vitro
assays at Bayer Pharma AG without claiming to deeply review all of the literature
available in each and every detail. In addition, phenotypic assays (Moffat et al.
2014) or label-free detection methods (Minor 2008) are not discussed. Although
this essay tries to cover the most relevant technological developments in the
field, it nevertheless may express personal preferences and peculiarities of the
author's approach to state-of-the-art cell-based assay development. For
additional reviews covering the actual field, see Wunder et al. (2008) and
Michelini et al. (2010).
PMID- 26424720
TI - Psychometric Properties of the Screen for Child Anxiety Related Emotional
Disorders (SCARED) in a Non-Clinical Sample of Children and Adolescents in Saudi
Arabia.
AB - This paper examined the reliability, convergent validity and factor structure of
the self-report Screen for Child Anxiety Disorders (SCARED; Birmaher et al. in J
Am Acad Child Adolesc Psychiatry 36:545-553, 1997) in a large community sample of
children and adolescents in Saudi Arabia. The questionnaire showed moderate to
high internal consistency and satisfactory test-retest reliability over a 2 week
period. In addition, there were significant positive correlations between
reported anxiety symptoms with parent report behavioural difficulties. The five
factor structure model of the SCARED also had a good model fit in this
population. The results showed that self-report anxiety symptoms decreased with
age (for boys and not girls) and were higher in adolescent girls. The results
suggest that the SCARED could be useful in this population to identify
individuals who are at risk of developing anxiety disorders in childhood with a
view to implementing prevention and intervention methods to ensure positive
developmental outcome over time.
PMID- 26424722
TI - The engagement of FDG PET/CT image quality and harmonized quantification: from
competitive to complementary.
AB - The use of (18)F-FDG PET/CT as a quantitative imaging biomarker requires
standardization and harmonization of imaging procedures and PET/CT system
performance to obtain repeatable and reproducible quantitative data. However, a
PET/CT system optimized to meet international quantitative standards is not
necessarily optimized for use as a diagnostic tool (i.e. for lesion
detectability). Several solutions have been proposed and validated, but until
recently none of them had been implemented commercially. Vendor-provided
solutions allowing the use of PET/CT both as a diagnostic tool and as a
quantitative imaging biomarker are therefore greatly needed and would be highly
appreciated. In this invited perspective one such solution is highlighted.
PMID- 26424723
TI - Evaluation of two methods for the use of diatoms in drowning cases.
AB - In this study, we compare digestive methods used in a forensic context to extract
diatoms (37 % hydrochloric acid) to a method recently described in Italian
protocols for analysis of benthic diatoms for ecological assessment of surface
water (hydrogen peroxide digestion). The two digestive methods were performed
using 5 g of brain, lung, liver, kidney, and bone marrow taken from the bodies of
10 drowning victims recovered from three different aquatic environments (ocean,
lakes, and rivers). Postmortem examination was performed on all bodies, but
aquatic samples were only analyzed in two cases. Tissue digestion was equal by
both methods. Hydrogen peroxide (H2O2) digestion resulted in better diatom
preservation, enabling identification of nine genera in all samples examined
versus three obtained using hydrochloride digestion. The ideal digestive method
to provide evidence for corroboration of a diagnosis of drowning still needs to
be established. However, the benthic diatoms protocol can be useful because it is
less chemically hazardous to the laboratory operator and supports better diatom
preservation for reliable taxonomic analysis.
PMID- 26424724
TI - GPs' adherence to guidelines for structured assessments of stroke survivors in
the community and care homes.
AB - BACKGROUND: Clinical practice guidelines recommend that stroke survivors' needs
be assessed at regular intervals after stroke. The extent to which GPs comply
with national guidance particularly for patients in care homes who have greatest
clinical complexity is unknown. OBJECTIVES: This study aimed to establish the
current clinical practice in the UK of needs assessment by GPs for stroke
survivors after hospital discharge for acute stroke. METHODS: Cross-sectional
online survey of current practice of GPs, using the national doctors.net network.
RESULTS: The survey was completed by 300 GPs who had on average been working for
14 years. The structured assessment of stroke survivors' needs was not offered by
31% of GPs, with no significant difference for level of provision in community or
care home settings. The outputs of reviews were added to patients' notes by 89%
of GPs and used to change management by 57%. Only half the GPs reported
integrating the information obtained into care plans and only a quarter of GPs
had a protocol for follow-up of identified needs. Analysis of free-text comments
indicated that patients in some care homes may receive more regular and
structured reviews. CONCLUSIONS: This survey suggests that at least one-third of
GPs provide no formal review of the needs of stroke patients and that in only a
minority are identified needs addressed in a structured way. Standardization is
required for what is included in reviews and how needs are being identified and
met.
PMID- 26424725
TI - Fixation of the Proximal Metatarsal Crescentic Osteotomy Using a Head Locking X
Plate.
AB - BACKGROUND: We present a new method to stabilize proximal crescentic osteotomies
(PCOs) for the correction of moderate to severe hallux valgus. METHODS: A single
center prospective study with a consecutive series of 72 patients (94 feet) with
a PCO was performed using a head locking X-plate. The primary aim was to
investigate the stability of the osteotomy, measuring the dorsal elevation of the
first metatarsal head, first cuneiform height, talus-first metatarsal angle, and
first metatarsal inclination pre- and postoperatively. A secondary outcome
assessed weight distribution during gait, quality of life, and radiologically
documented bone healing process. RESULTS: Ninety-three percent of the feet were
within +/-2 mm change for dorsal elevation of the first metatarsal head, and 72%
for the medial cuneiform height. Eighty-nine percent were within +/-4 degrees
change for the first metatarsal inclination, 73% for the talus-first metatarsal
angle, and 100% for the calcaneus pitch angle. The mean changes between pre- and
1-year postoperative were not significantly different for any of the stability
measurements except for the first metatarsal inclination angle. The SF36 showed a
significant improvement of physical function, general health, and decreased
bodily pain. Harris mat footprints showed a decrease of 46% underneath the second
and a pressure decrease of 40% underneath the third metatarsal head. CONCLUSION:
This technique, of using a head locking X-plate to stabilize the PCO, showed
satisfactory and reproducible results in terms of stability, clinical outcome,
bone healing, and patient satisfaction. The plate provided substantial support
for the PCO resulting in adequate and easy fixation. LEVEL OF EVIDENCE: Level IV,
retrospective case series.
PMID- 26424726
TI - Polymerase chain reaction blood tests for the diagnosis of invasive aspergillosis
in immunocompromised people.
AB - BACKGROUND: Invasive aspergillosis (IA) is the most common life-threatening
opportunistic invasive mould infection in immunocompromised people. Early
diagnosis of IA and prompt administration of appropriate antifungal treatment are
critical to the survival of people with IA. Antifungal drugs can be given as
prophylaxis or empirical therapy, instigated on the basis of a diagnostic
strategy (the pre-emptive approach) or for treating established disease.
Consequently there is an urgent need for research into both new diagnostic tools
and drug treatment strategies. Newer methods such as polymerase chain reaction
(PCR) to detect fungal nucleic acids are increasingly being investigated.
OBJECTIVES: To provide an overall summary of the diagnostic accuracy of PCR-based
tests on blood specimens for the diagnosis of IA in immunocompromised people.
SEARCH METHODS: We searched MEDLINE (1946 to June 2015) and EMBASE (1980 to June
2015). We also searched LILACS, DARE, Health Technology Assessment, Web of
Science and Scopus to June 2015. We checked the reference lists of all the
studies identified by the above methods and contacted relevant authors and
researchers in the field. SELECTION CRITERIA: We included studies that: i)
compared the results of blood PCR tests with the reference standard published by
the European Organisation for Research and Treatment of Cancer/Mycoses Study
Group (EORTC/MSG); ii) reported data on false-positive, true-positive, false
negative and true-negative results of the diagnostic tests under investigation
separately; and iii) evaluated the test(s) prospectively in cohorts of people
from a relevant clinical population, defined as a group of individuals at high
risk for invasive aspergillosis. Case-control studies were excluded from the
analysis. DATA COLLECTION AND ANALYSIS: Authors independently assessed quality
and extracted data. For PCR assays, we evaluated the requirement for either one
or two consecutive samples to be positive for diagnostic accuracy. We
investigated heterogeneity by subgroup analyses. We plotted estimates of
sensitivity and specificity from each study in receiver operating characteristics
(ROC) space and constructed forest plots for visual examination of variation in
test accuracy. We performed meta-analyses using the bivariate model to produce
summary estimates of sensitivity and specificity. MAIN RESULTS: Eighteen primary
studies, corresponding to 19 cohorts and 22 data sets, published between 2000 and
2013 were included in the meta-analyses, with a median prevalence of IA (proven
or probable) of 12.0% (range 2.5 to 30.8 %). The majority of people had received
chemotherapy for a haematological malignancy or had undergone a hematopoietic
stem cell transplant. Several PCR techniques were used among the included
studies. The sensitivity and specificity of PCR for the diagnosis of IA varied
according to the interpretative criteria used to define a test as positive. The
mean sensitivity and specificity were 80.5% (95% CI; 73.0 to 86.3) and 78.5%
(67.8 to 86.4) for a single positive test result, and 58.0% (36.5 to 76.8) and
96.2% (89.6 to 98.6) for two consecutive positive test results. AUTHORS'
CONCLUSIONS: PCR shows moderate diagnostic accuracy when used as screening tests
for IA in high-risk patient groups. Importantly the sensitivity of the test
confers a high negative predictive value (NPV) such that a negative test allows
the diagnosis to be excluded. Consecutive positives show good specificity in
diagnosis of IA and could be used to trigger radiological and other
investigations or for pre-emptive therapy in the absence of specific radiological
signs when the clinical suspicion of infection is high. When a single PCR
positive test is used as diagnostic criterion for IA in a population of 100
people with a disease prevalence of 13.0% (overall mean prevalence), three people
with IA would be missed (sensitivity 80.5%, 19.5% false negatives), and 19 people
would be unnecessarily treated or referred for further tests (specificity of
78.5%, 21.5% false positives). If we use the two positive test requirement in a
population with the same disease prevalence, it would mean that six IA people
would be missed (sensitivity 58.0%, 42.1% false negatives) and three people would
be unnecessarily treated or referred for further tests (specificity of 96.2%,
3.8% false positives). Galactomannan and PCR have good NPV for excluding disease
but the low prevalence of disease limits the ability to rule in a diagnosis. The
biomarkers are detecting different aspects of disease and the combination of both
together is likely to be more useful.
PMID- 26424728
TI - The Impact of Fractional Flow Reserve on Revascularization.
AB - INTRODUCTION: Fractional flow reserve (FFR) is recommended by society guidelines
for assessment of the hemodynamic significance of intermediate coronary lesions
when non-invasive evidence of myocardial ischemia is unavailable. However, the
prevalence of FFR usage in current practice and how FFR values impact
revascularization decisions are not well known. METHODS: At a single-center
Veterans Administration Hospital, all subjects referred for coronary angiography
for any indication from the period from May 2012 until January 2014 were
prospectively entered into a database. FFR was measured in all intermediate
coronary lesions (30-70% stenosis). Based on the FFR results, the lesions were
categorized into 3 different groups: FFR > 0.80 (non-ischemic), FFR 0.75-0.80
(gray zone), and FFR < 0.75 (ischemic). RESULTS: A total of 1482 cardiac
catheterizations were performed during the study period. FFR was performed in 347
(23%) of these procedures. The total numbers of intermediate coronary lesions
evaluated with FFR were 429. The mean FFR value was 0.79 (median = 0.80;
interquartile range 0.64-0.96). Among 211 non-ischemic lesions, revascularization
was deferred in 201 (95%). In the gray-zone group (73 lesions), 35 (48%) lesions
were treated with percutaneous coronary intervention (PCI), 11 (15%) lesions were
referred for coronary artery bypass grafting surgery (CABG), and 27 (37%) lesions
were treated medically. In the ischemic group (145 lesions), 82 (57%) lesions
were treated with PCI, 41 (28%) lesions were referred for CABG, and 22 (15%)
lesions were treated medically. CONCLUSION: At a Veterans Administration
Hospital, FFR was performed in approximately one out of four total
catheterizations. FFR documented lack of ischemia in about half of the
intermediate coronary lesions, and thus reduced the need for many
revascularization procedures.
PMID- 26424727
TI - Fast Dating Using Least-Squares Criteria and Algorithms.
AB - Phylogenies provide a useful way to understand the evolutionary history of
genetic samples, and data sets with more than a thousand taxa are becoming
increasingly common, notably with viruses (e.g., human immunodeficiency virus
(HIV)). Dating ancestral events is one of the first, essential goals with such
data. However, current sophisticated probabilistic approaches struggle to handle
data sets of this size. Here, we present very fast dating algorithms, based on a
Gaussian model closely related to the Langley-Fitch molecular-clock model. We
show that this model is robust to uncorrelated violations of the molecular clock.
Our algorithms apply to serial data, where the tips of the tree have been sampled
through times. They estimate the substitution rate and the dates of all ancestral
nodes. When the input tree is unrooted, they can provide an estimate for the root
position, thus representing a new, practical alternative to the standard rooting
methods (e.g., midpoint). Our algorithms exploit the tree (recursive) structure
of the problem at hand, and the close relationships between least-squares and
linear algebra. We distinguish between an unconstrained setting and the case
where the temporal precedence constraint (i.e., an ancestral node must be older
that its daughter nodes) is accounted for. With rooted trees, the former is
solved using linear algebra in linear computing time (i.e., proportional to the
number of taxa), while the resolution of the latter, constrained setting, is
based on an active-set method that runs in nearly linear time. With unrooted
trees the computing time becomes (nearly) quadratic (i.e., proportional to the
square of the number of taxa). In all cases, very large input trees (>10,000
taxa) can easily be processed and transformed into time-scaled trees. We compare
these algorithms to standard methods (root-to-tip, r8s version of Langley-Fitch
method, and BEAST). Using simulated data, we show that their estimation accuracy
is similar to that of the most sophisticated methods, while their computing time
is much faster. We apply these algorithms on a large data set comprising 1194
strains of Influenza virus from the pdm09 H1N1 Human pandemic. Again the results
show that these algorithms provide a very fast alternative with results similar
to those of other computer programs. These algorithms are implemented in the LSD
software (least-squares dating), which can be downloaded from http://www.atgc
montpellier.fr/LSD/, along with all our data sets and detailed results. An Online
Appendix, providing additional algorithm descriptions, tables, and figures can be
found in the Supplementary Material available on Dryad at
http://dx.doi.org/10.5061/dryad.968t3.
PMID- 26424729
TI - Non-utilization of the Pap Test Among Women with Frequent Health System Contact.
AB - Despite improvements in health access, many underserved women abstain from
cervical cancer screening. A self-administered questionnaire was used to identify
factors determining whether medically underserved women attending a safety net
health system regularly are screened for cervical cancer. Approximately 11 % of
study subjects had never received a Pap test despite an average of nearly four
clinic visits in the preceding 12 months. Never screeners were significantly
younger, more likely to be Hispanic, non-U.S. born and less likely to have
healthcare continuity. In multivariable analysis, odds for never screening were
independently lower among women with male partner support (aOR 0.29) and
physician's recommendation for screening (aOR 0.34) and higher among women who
believed screening visits are too long (aOR 2.53). Educating male partners of
Hispanic and immigrant women in addition to addressing recognized situational
barriers may help to improve cervical cancer screening rates.
PMID- 26424730
TI - Acanthocephalan-related variation in the pattern of energy storage of a
behaviorally and physiologically modified host: field data.
AB - The acanthocephalan parasite Acanthocephalus dirus infects the freshwater isopod
Caecidotea intermedius as an intermediate host before completing its life cycle
in a fish. Transmission to the definitive host occurs after the parasite has
reached the cystacanth stage, and development into this stage is associated with
changes in several behavioral and physiological traits of the host. Given the
potential importance of host energy availability to trait modification, we
examined the relationship between cystacanth-stage infection and energy storage
of adult isopods. Six samples of infected and uninfected male C. intermedius were
collected from a population in March, April, and May during which time cystacanth
stage A. dirus dominate infections and modification of behavior and physiology
occurs in nature. Biochemical assays revealed that infected male C. intermedius
contained more glycogen and more lipid than uninfected males and that this
difference was present throughout the sampling period, which represents the
entire adult phase of the host's life. Additional analysis revealed that infected
and uninfected males differed in their pattern of allocation to each energy
source and that host lipid levels were negatively correlated with parasite
intensity. We propose that the typical pattern of allocation and storage of host
energy appears to be disrupted by A. dirus infection and that the changes are
more likely to favor the parasite than the host.
PMID- 26424731
TI - Dissociation between exercise-induced reduction in liver fat and changes in
hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic
fatty liver disease.
AB - Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ
(hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is
an effective treatment for lowering liver fat but its effect on IR in NAFLD is
unknown. We aimed to determine whether supervised exercise in NAFLD would reduce
liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue)
insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks
exercise supervision (n=38) or counselling (n=31) without dietary modification.
All participants underwent MRI/spectroscopy to assess changes in body fat and in
liver and skeletal muscle triglyceride, before and following
exercise/counselling. To quantify changes in hepatic and peripheral insulin
sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage
hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown
as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20
counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29,
35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study
(12/12 exercise and 7/12 counselling completed the clamp studies). Supervised
exercise mediated a greater reduction in liver fat/water percentage than
counselling [Delta mean change 4.7% (0.01, 9.4); P<0.05], which correlated with
the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise,
peripheral insulin sensitivity significantly increased (following high-dose
insulin) despite no significant change in hepatic glucose production (HGP;
following low-dose insulin); no changes were observed in the control group.
Although supervised exercise effectively reduced liver fat, improving peripheral
IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR.
PMID- 26424732
TI - The effectiveness of microsurgical fenestration for middle fossa arachnoid cysts
in children.
AB - OBJECTIVE: Although middle fossa arachnoid cysts (MFACs) are common, the optimal
surgical treatment for these lesions remains controversial. In this study, we
present our experiences of treating MFACs by microsurgical fenestration and
evaluate its effectiveness. METHODS: We performed retrospective review of 28
patients who underwent microsurgical fenestration for MFACs between May 2003 and
December 2014. We reviewed patient characteristics and treatment outcomes
including age, sex, symptoms, complicating hydrocephalus, Gallasi classification,
change in cyst size after surgery, complicating subdural hygroma, symptom
resolution, regrowth of the cyst, and reoperation (including additional CSF
diversion). RESULTS: Twenty-eight MFACs in 28 patients were investigated. The
average age at the time of surgery was 61.6 months. The average follow-up
duration was 53.5 months. After surgery, 19 (90.5 %) of 21 patients with
symptomatic MFACs experienced improvements. The cysts decreased in size in all
cases (100 %, 28/28) and disappeared in three cases (11 %, 3/28). None of the
cases experienced regrowth of the cyst. Subdural hygroma was identified in 23
cases (82.1 %) at the immediate postoperative period. Hygroma was asymptomatic in
all cases but one. Hygroma disappeared in 19 cases (83 %) and decreased in size
in three cases (13 %) in the long term. Only one case (4 %) required an
additional subdural-peritoneal shunt. The rate of CSF diversion after the
fenestration was significantly higher in patients with preoperative ventricular
dilation (p = 0.0002). CONCLUSION: Microsurgical fenestration for pediatric MFACs
was considered to be safe and effective. Although subdural hygroma developed in
significant number of patients at the immediate postoperative period, it was
mostly asymptomatic and disappeared or decreased in size in the long term.
PMID- 26424734
TI - Suicide Risk of Heroin Dependent Subjects in Lebanon.
AB - The aim is to determine the frequency of suicidal behavior and associated factors
among heroin dependent inpatients. 61 heroin dependent inpatients (vs. 61
controls) were assessed on their pattern of substance use, impulsivity,
depression and suicidal behavior. 37.7 % of patients had a personal history of
suicidal attempt (SA), 14.8 % had current suicidal ideation. SA was associated to
younger age at first substance use and to higher rates of depression and
impulsivity. IV heroin overdose was the most frequent mode of SA (47.8 %). Long
duration, multiple drug use, and family history of suicide were associated with
higher risk of suicide among lebanese patients.
PMID- 26424733
TI - Elevated low-density lipoprotein cholesterol is independently associated with
obstructive sleep apnea: evidence from a large-scale cross-sectional study.
AB - BACKGROUND: Lipid metabolism disorder is recognized to be associated with
obstructive sleep apnea (OSA); however, inconsistent results have been reported.
The aim of this study was to evaluate the association between lipid profile and
OSA with adjustments for multiple confounding factors. METHODS: In total, 2983
subjects were recruited from the Shanghai Sleep Health Study (SSHS) during 2007
2013. Data for overnight polysomnography (PSG) parameters, serum lipids, fasting
blood glucose, insulin levels, and anthropometric measurements were collected.
Multivariable logistic regression analyses were used to determine the correlation
between lipid profile and OSA with adjustments for confounders including lipids,
age, gender, Epworth sleepiness scale, body mass index, waist/hip ratio, glucose,
insulin resistance, hypertension, and smoking. RESULTS: The prevalence of hyper
total cholesterol (TC), hyper triglycerides, hypo high-density lipoprotein
cholesterol, hyper low-density lipoprotein cholesterol (LDL-C), hyper
apolipoprotein (apo) A-I, and hyper apoB differed significantly between the non
OSA and OSA patients. Without considering the interaction across different
lipids, TC, LDL-C, and apoB were independently associated with OSA in primary
multivariable logistic regression analyses; the odds ratios (ORs) and 95 %
confidence intervals (CIs) were 1.262 (1.109-1.438), 1.432 (1.233-1.664), and
5.582 (2.643-11.787), respectively. However, only LDL-C (OR = 1.430, 95 % CI =
1.221-1.675) was found to be an independent risk factor for OSA in further
multivariable logistic regression analyses. CONCLUSIONS: We demonstrated that
patients with OSA had a higher percentage of dyslipidemia than subjects without
OSA. Of the various components in serum lipid, only LDL-C was independently
associated with OSA.
PMID- 26424735
TI - Middle School as a Developmental Niche for Civic Engagement.
AB - The present study investigated how school climate, school connectedness and
academic efficacy beliefs inform emergent civic engagement behaviors among middle
school youth of color. These associations were examined both concurrently and
longitudinally using a developmentally appropriate measure of civic engagement.
Data were drawn from two subsamples of a larger study of social/emotional
development in middle school (cross-sectional sample n = 324; longitudinal sample
n = 232), M = 12 years old, 46 % female, 53 % male. Forty-two percent (42.2 %) of
the sample self-identified as African American, 19.8 % as Multiracial or Mixed,
19.4 % as Latino, 11.6 % as Asian American or Pacific Islander, 11.6 % identified
as Other, and 5.2 % as Native American. The study tested and found support for a
latent mediation model in which more positive perceptions of school climate were
positively related to school connectedness, and this in turn, was positively
associated with civic engagement; school climate was also positively associated
with academic-self-efficacy beliefs, but such beliefs did not mediate the climate
civic engagement association. Implications for future research and practice are
discussed.
PMID- 26424736
TI - Effects of treadmill running and rutin on lipolytic signaling pathways and TRPV4
protein expression in the adipose tissue of diet-induced obese mice.
AB - To explore the effects of rutin and exercise on high-fat diet (HFD)-induced
disrupted lipolytic signaling, adenosine 5'-monophosphate (AMP)-activated protein
kinase (AMPK) signaling, transient receptor potential cation channel subfamily V
member 4 (TRPV4) and its associated protein expression, and whether depot
specific effects existed. C57BL/6J mice were randomized into five groups: chow
group, HFD, HFD plus rutin intervention group (HR), HFD combined with treadmill
running group (HE), and HFD combined with treadmill running and rutin
intervention group (HRE). At the end of the 16-week intervention, lipolytic
markers, AMPK signaling pathways, TRPV4, and peroxisome proliferator-activated
receptor gamma coactivator 1alpha + beta (PGC-1alpha + beta) from adipose tissue
were measured by western blotting. In epididymal adipose tissue, HFD resulted in
significant reduction in the phosphorylation of hormone sensitive lipase at
serine660 (p-HSL660), perilipin A, phosphoenolpyruvate carboxykinase (PEPCK), p
AMPK, and p-acetyl-CoA carboxylase (ACC) protein expression. Exercise
intervention and exercise plus rutin completely restored p-HSL660, perilipin A,
PEPCK, p-AMPK, and p-ACC protein expression to normal level. HFD and HR groups
have reduced expression of PGC-1alpha + beta, exercise, and exercise plus rutin
completely restored PGC-1alpha + beta expression to normal level. In subcutaneous
adipose tissue, HFD elevated TRPV4, exercise, and exercise plus rutin completely
reduced TRPV4 to normal level. HR, HE, and HRE group have increased PGC-1alpha +
beta. In conclusion, depot-specific effects existed in regards to how rutin and
exercise affect lipolytic signaling and p-AMPK, as well as TRPV4 and PGC-1alpha +
beta expression.
PMID- 26424738
TI - ASCO Reveals Additional Promising Results With Immunotherapies.
PMID- 26424737
TI - Molecular epidemiology of MRSA in 13 ICUs from eight European countries.
AB - OBJECTIVES: The European epidemiology of MRSA is changing with the emergence of
community-associated MRSA (CA-MRSA) and livestock-associated MRSA (LA-MRSA). In
this study, we investigated the molecular epidemiology of MRSA during 2 years in
13 ICUs in France, Greece, Italy, Latvia, Luxemburg, Portugal, Slovenia and
Spain. METHODS: Surveillance cultures for MRSA from nose and wounds were obtained
on admission and twice weekly from all patients admitted to an ICU for >=3 days.
The first MRSA isolate per patient was genotyped in a central laboratory by MLST,
spa typing, agr typing and SCCmec (sub)typing. Risk factors for patients with an
unknown history of MRSA colonization were identified. RESULTS: Overall, 14 390
ICU patients were screened, of whom 8519 stayed in an ICU for >=3 days. Overall
MRSA admission prevalence was 3.9% and ranged from 1.0% to 7.0% for individual
ICUs. Overall MRSA acquisition rate was 2.5/1000 patient days at risk and ranged
from 0.2 to 8/1000 patient days at risk per ICU. In total, 557 putative MRSA
isolates were submitted to the central laboratory for typing, of which 511 (92%)
were confirmed as MRSA. Each country had a distinct epidemiology, with ST8-IVc
(UK-EMRSA-2/-6, USA500) being most prevalent, especially in France and Spain, and
detected in ICUs in five of eight countries. Seventeen (3%) and three (<1%)
isolates were categorized as CA-MRSA and LA-MRSA, respectively. Risk factors for
MRSA carriage on ICU admission were age >70 years and hospitalization within 1
year prior to ICU admission. CONCLUSIONS: The molecular epidemiology of MRSA in
13 European ICUs in eight countries was homogeneous within, but heterogeneous
between, countries. CA-MRSA and LA-MRSA genotypes and Panton-Valentine leucocidin
producing isolates were detected sporadically.
PMID- 26424739
TI - Study Finds Black Women Have Denser Breast Tissue Than White Women.
PMID- 26424740
TI - Elective Neck Dissection in Early Oral Cancer: Debate Resolved.
PMID- 26424743
TI - Banked Donor T-Cells Treat Virus-Related B Cell Disorder when Rituximab Fails.
PMID- 26424744
TI - Authors' reply to Elshimy.
PMID- 26424745
TI - Plymouth medical school is committed to producing GPs of the future.
PMID- 26424746
TI - Frozen elephant trunk procedure for extensive pneumococcal thoracic aortitis.
AB - Infectious arteritis is an insidious condition commonly associated with a long
diagnostic delay. We report the management of extensive pneumococcal thoracic
aortitis in a 64-year-old woman. The frozen elephant trunk procedure was
performed to repair the aortic arch. Prolonged aortic wall cultures were positive
for Streptococcus pneumoniae. Late follow-up imaging at 36 months demonstrated no
sign of recurrence around the hybrid vascular graft in the thoracic aorta.
PMID- 26424747
TI - Prognostic Indicators for Salvage Surgery of Recurrent Sinonasal Malignancy.
AB - OBJECTIVE: Identify prognostic factors after salvage surgery for recurrent
sinonasal malignancy (SNM). STUDY DESIGN: Case series with chart review. SETTING:
University of Pittsburgh Medical Center. SUBJECTS: Forty-two patients who
underwent curative surgery for locally recurrent SNM +/- adjuvant therapy from
June 5, 2000, to December 19, 2012. Patients without follow-up were excluded.
METHODS: Chart review with established prognostic indicators for primary
malignancies. Statistical analysis included Kaplan-Meier log-rank test, Fisher's
exact test, Student's t test, and Cox regression. RESULTS: Forty-two patients met
inclusion criteria: 38.5% developed a second recurrence, and 21.4% had metastases
following treatment. The average disease-free interval (DFI) was 26.9 months
(range, 2-90 months). DFI was significantly affected by ethmoid versus nonethmoid
site (P = .049), histology (P = .012), carotid artery involvement (P = .008),
perineural extension (P = .006), and clival invasion (P = .015). The overall
survival rates at 6 months, 12 months, and 5 years following surgery were 83.3%,
69%, and 47.6%, respectively. Survival was affected by histology (P = .014),
stratified grade (P = .042), tumor extension into the orbit (P = .019), carotid
artery (P = .001), perineural space (P = .028), and clivus (P = .022).
Complications occurred in 28.6% of patients and were associated with histology (P
= .04). Length of hospital stay related to treatment was affected by histology (P
= .009), grade (P = .013), and postoperative complication (P < .001). The median
percentage of time hospitalized was 8%, and 43% of patients who died within 12
months spent >10% of their remaining days in the hospital. CONCLUSION: High-risk
histologic subtype (melanoma, sinonasal undifferentiated carcinoma,
adenocarcinoma, neuroendocrine cancer, sarcoma, and squamous cell carcinoma),
grade, and orbital and skull base involvement negatively affect survival and/or
DFI for patients with local recurrence of SNM. Improved stratification of
patients can be used to guide decision making for patients with recurrent SNM and
to avoid inappropriate surgery.
PMID- 26424748
TI - Marketing a Healthy Mind, Body, and Soul: An Analysis of How African American Men
View the Church as a Social Marketer and Health Promoter of Colorectal Cancer
Risk and Prevention.
AB - The Centers for Disease Control and Prevention ranks colorectal cancer (CRC) as
the third most commonly diagnosed cancer among men in the United States; African
American (AA) men are at even greater risk. The present study was from a larger
study that investigates the church's role as a social marketer of CRC risk and
prevention messages, and whether religiously targeted and tailored health
promotion materials will influence screening outcome. We used an integrated
theoretical approach to explore participants' perceptions of CRC risk and
prevention and how promotion messages should be developed and socially marketed
by the church. Six focus groups were conducted with men from predominately AA
churches in the Midwest. Themes from focus group discussions showed participants
lacked knowledge about CRC, feared cancer diagnosis, and feared the procedure for
screening. Roles of masculinity and the mistrust of physicians were also emergent
themes. Participants did perceive the church as a trusted marketer of CRC but
believed that promotional materials should be cosponsored and codeveloped by
reputable health organizations. Employing the church as a social marketer of CRC
screening promotion materials may be useful in guiding health promotions and
addressing barriers that are distinct among African American men.
PMID- 26424749
TI - The NC11 domain of human collagen XVI induces vasculogenic mimicry in oral
squamous cell carcinoma cells.
AB - Collagen XVI, a fibril-associated collagen with interrupted triple helix (FACIT)
collagen, is involved in oral squamous cell carcinoma (OSCC) and glioblastoma
progression. The NC11 domain of collagen XVI has been described previously with a
strong implication in physiological processes. We detected the non-collagenous
(NC) 11-domain in supernatants of OSCC cells after recombinant expression of full
length collagen XVI and in sera from OSCC patients and healthy individuals.
Stable expression of NC11-green fluorescent protein (GFP) fusion protein in OSCC
cells initiated proliferation control and block of anchorage-independent growth.
Moreover, the NC11 domain triggered the generation of tubular-like net structures
on laminin-rich matrix in contrast to mock-GFP control cells and cells expressing
full-length collagen XVI. Taqman(r) quantitative PCR and diaminobenzidine
staining in 2D- and 3D cell culture revealed a significantly increased gene and
protein expression of VEGFR1, VEGFR2 and uPAR in recombinant NC11-GFP-expressing
cells. Specific VEGF receptor inhibition with Axitinib or fetal calf serum heat
inactivation prevented formation of tubular-like net structures. Accordantly,
NC11-GFP coated culture slides led to an increase of focal adhesion contact
formation and the upregulation of VEGFR1 and uPAR in three different non
transfected OSCC cell lines. In summary, we suggest that the NC11 domain of
collagen XVI is a potential biomarker for OSCC and triggers vasculogenic mimicry
via upregulation of endothelial receptors VEGFR1, VEGFR2 and uPAR in 2D- and 3D
OSCC cell culture conditions.
PMID- 26424750
TI - The mycotoxin aflatoxin B1 stimulates Epstein-Barr virus-induced B-cell
transformation in in vitro and in vivo experimental models.
AB - Although Epstein-Barr virus (EBV) infection is widely distributed, certain EBV
driven malignancies are geographically restricted. EBV-associated Burkitt's
lymphoma (eBL) is endemic in children living in sub-Saharan Africa. This
population is heavily exposed to food contaminated with the mycotoxin aflatoxin
B1 (AFB1). Here, we show that exposure to AFB1 in in vitro and in vivo models
induces activation of the EBV lytic cycle and increases EBV load, two events that
are associated with an increased risk of eBL in vivo. AFB1 treatment leads to the
alteration of cellular gene expression, with consequent activations of signaling
pathways, e.g. PI3K, that in turn mediate reactivation of the EBV life cycle.
Finally, we show that AFB1 triggers EBV-driven cellular transformation both in
primary human B cells and in a humanized animal model. In summary, our data
provide evidence for a role of AFB1 as a cofactor in EBV-mediated carcinogenesis.
PMID- 26424752
TI - To Cut ... or Not?
PMID- 26424753
TI - Biomechanical Analysis of Simulated Clinical Testing and Reconstruction of the
ALL: Letter to the Editor.
PMID- 26424754
TI - Biomechanical Analysis of Simulated Clinical Testing and Reconstruction of the
ALL: Response.
PMID- 26424755
TI - The Effectiveness of ESWT in Lower Limb Tendinopathy: Letter to the Editor.
PMID- 26424756
TI - The Effectiveness of ESWT in Lower Limb Tendinopathy: Response.
PMID- 26424757
TI - Is there a role yet for new direct oral anticoagulants in cancer patients?
PMID- 26424751
TI - Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer.
AB - Genome-wide association studies have identified 20 genomic regions associated
with risk of epithelial ovarian cancer (EOC), but many additional risk variants
may exist. Here, we evaluated associations between common genetic variants
[single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC
risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15
397 patients with invasive EOC and controls. We found evidence of associations
with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P
<= 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with
serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes
from the 1000 genomes project identified a slightly more significant association
for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95%
CI 1.11-1.24, P = 1.1*10(-7)). We identified 293 variants in the region with
likelihood ratios of less than 1:100 for representing the causal variant.
Functional annotation identified 25 candidate SNPs that alter transcription
factor binding sites within regulatory elements active in EOC precursor tissues.
In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly
higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72*10(
8)). We also identified an association between genotypes of the candidate causal
SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70*10(
8)). These data suggest that common variants at 22q12.1 are associated with risk
of serous EOC and CHEK2 as a plausible target susceptibility gene.
PMID- 26424759
TI - The Association Between PD-L1 Expression and the Clinical Outcomes to Vascular
Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Clear Cell
Renal Cell Carcinoma.
AB - BACKGROUND: Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase
inhibitors (TKIs) are used as the first-line treatment for patients with
metastatic clear cell renal cell carcinoma (mCCRCC). Recently, programmed death-1
(PD-1) and programmed death ligand-1 (PD-L1) blockade emerged as promising
therapy for renal cell carcinoma. However, the expression pattern and prognostic
implication of programmed death-ligands (PD-Ls) in mCCRCC patients receiving VEGF
TKI remain unclear. PATIENTS AND METHODS: PD-L1 and PD-L2 expression in tumor
cells and the quantities of PD-1+ tumor-infiltrating lymphocytes were
immunohistochemically evaluated in 91 mCCRCC patients treated with VEGF-TKI, and
their associations with VEGF-TKI responsiveness and clinical outcome were
analyzed. RESULTS: PD-L1 immunopositivity was observed in 17.6% and significantly
associated with a high International Society of Urological Pathology grade (p =
.031) and sarcomatoid features (p = .014). PD-L2 immunopositivity was observed in
39.6% and was not associated with any of the assessed clinicopathological
variables. PD-L1-positive cases showed poor VEGF-TKI responsiveness (p = .012)
compared with PD-L1-negative cases. In univariate survival analysis, PD-L1
immunopositivity was significantly associated with shorter overall survival (OS)
(p = .037) and progression-free survival (PFS) (p = .043). Multivariate survival
analysis revealed that PD-L1 expression was independently associated with poor OS
(p = .038) and PFS (p = .013) in addition to tumor necrosis (p = .006; p = .029,
respectively) and Memorial Sloan Kettering Cancer Center score (p = .018; p =
.032, respectively). PD-L2 expression was neither associated with VEGF-TKI
responsiveness nor patients' outcome. CONCLUSION: PD-L1 expression was
significantly related to lack of VEGF-TKI responsiveness and independently
associated with shorter survival in mCCRCC patients after VEGF-TKI treatment. PD
L1 may have a predictive and prognostic value for determining the value of VEGF
TKI treatment in patients with mCCRCC. IMPLICATIONS FOR PRACTICE: Vascular
endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are
essential for the treatment of metastatic renal cell carcinoma patients, but the
treatment suffers from a lack of predictive markers. This study demonstrates that
PD-L1 expression is a predictor for unfavorable response to VEGF-TKI and a
prognostic indicator for poor overall survival and progression-free survival in
patients with metastatic clear cell renal cell carcinoma receiving VEGF-TKI.
PMID- 26424758
TI - Familial Gastric Cancers.
AB - Although the majority of gastric carcinomas are sporadic, approximately 10% show
familial aggregation, and a hereditary cause is determined in 1%-3% cases. Of
these, hereditary diffuse gastric cancer is the most recognized predisposition
syndrome. Although rare, the less commonly known syndromes also confer a markedly
increased risk for development of gastric cancer. Identification and
characterization of these syndromes require a multidisciplinary effort involving
oncologists, surgeons, genetic counselors, biologists, and pathologists. This
article reviews the molecular genetics, clinical and pathologic features,
surveillance guidelines, and preventive measures of common and less common
hereditary gastric cancer predisposition syndromes.
PMID- 26424760
TI - Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma
Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group
(UN10-06).
AB - BACKGROUND: KIT has been suggested to be a potential therapeutic target for
malignant melanoma. We evaluated the antitumor activity and safety of the KIT
inhibitor nilotinib in metastatic melanoma patients harboring KIT gene mutations
or amplifications. METHODS: We conducted a phase II multicenter trial of
nilotinib in metastatic malignant melanoma with KIT mutations or amplifications.
Patients received 400 mg oral nilotinib twice daily. The primary endpoint was
response rate, and if seven or more responders were observed from the cumulative
36 patients, nilotinib would be considered worthy of further testing in this
study population. RESULTS: Between October 2009 and June 2013, 176 patients
underwent molecular screening for KIT gene aberrations, and 42 patients harboring
KIT gene mutations and/or amplification were enrolled in the study. Overall, 25
(59.5%), 15 (35.7%), and 2 (4.8%) patients had KIT mutations, KIT amplifications,
and both KIT mutations and amplification, respectively. Of the 42 enrolled
patients, 1 patient achieved complete response, 6 patients achieved partial
response, and 17 patients achieved stable disease, resulting in an overall
response rate of 16.7% (95% confidence interval [CI]: 5.4%-28.0%) and a disease
control rate of 57.1% (95% CI: 42.1%-72.1%). The median duration of response was
34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KIT mutations
(exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification
only. CONCLUSION: Although this study did not meet its primary endpoint of
response rate, nilotinib showed durable response in a subset of metastatic
melanoma patients with specific KIT mutations. IMPLICATIONS FOR PRACTICE: KIT
aberration can be detected in a subset of metastatic melanoma patients. This
phase II trial showed that nilotinib demonstrates durable response in a subset of
patients with KIT mutations. The safety profile was very tolerable. This study
suggests that a KIT inhibitor may benefit a small subset of metastatic melanoma
patients with KIT mutations.
PMID- 26424761
TI - Assessing patient-centred care through direct observation of clinical encounters.
PMID- 26424762
TI - Observation for assessment of clinician performance: a narrative review.
AB - BACKGROUND: Video recorded and in-person observations are methods of quality
assessment and monitoring that have been employed in high risk industries. In the
medical field, observations have been used to evaluate the quality and safety of
various clinical processes. This review summarises studies utilising video
recorded or in-person observations for assessing clinician performance in
medicine and surgery. METHODS: A search of MEDLINE (PubMed) was conducted using a
combination of medical subject headings (MeSH) terms. Articles were included if
they described the use of in-person or video recorded observations to assess
clinician practices in three categories: (1) teamwork and communication between
clinicians; (2) errors and weaknesses in practice; and (3) compliance and
adherence to interventions or guidelines. RESULTS: The initial search criteria
returned 3215 studies, 223 of which were identified for full text review. A total
of 69 studies were included in the final set of literature. Observations were
most commonly used in data dense and high risk environments, such as the
emergency department or operating room. The most common use was for assessing
teamwork and communication factors. CONCLUSIONS: Observations are useful for the
improvement of healthcare delivery through the identification of clinician lapses
and weaknesses that affect quality and safety. Limitations of observations
include the Hawthorne effect and the necessity of trained observers to capture
and analyse the notes or videos. The comprehensive, subtle and sensitive
information observations provided can supplement traditional quality assessment
methods and inform targeted interventions to improve patient safety and the
quality of care.
PMID- 26424763
TI - Point-of-care decision support for reducing inappropriate test use: easier said
than done.
PMID- 26424764
TI - Community Palliative Care Nurses' Challenges and Coping Strategies on Delivering
Home-Based Pediatric Palliative Care.
AB - OBJECTIVE: The aim of this study was to explore the experience of community
palliative care nurses providing home care to children. METHOD: A qualitative
study was conducted at the 3 community palliative care provider organizations in
greater Kuala Lumpur from August to October 2014. Data were collected with
semistructured interviews with 16 nurses who have provided care to children and
was analyzed using thematic analysis. Two categories were identified: (1)
challenges nurses faced and (2) coping strategies. The themes identified from the
categories are (1) communication challenges, (2) inadequate training and
knowledge, (3) personal suffering, (4) challenges of the system, (5)
intrapersonal coping skills, (6) interpersonal coping strategies, and (7)
systemic supports. CONCLUSIONS: These results reinforces the need for integration
of pediatric palliative care teaching and communication skills training into all
undergraduate health care programs. Provider organizational support to meet the
specific needs of the nurses in the community can help retain them in their role.
It will also be important to develop standards for current and new palliative
care services to ensure delivery of quality pediatric palliative care.
PMID- 26424765
TI - Genomic manipulations in alkaliphilic haloarchaea demonstrated by a gene
disruption in Natrialba magadii.
AB - Alkaliphilic haloarchaea, a distinct physiological group from the closely related
neutrophilic haloarchaea, represent an underutilized resource for basic research
and industrial applications. In contrast to the neutrophilic haloarchaea, no
reports on genomic manipulations in haloalkaliphiles have been published until
now. Genomic manipulations via homologous recombination are useful for basic
research. In this study, we demonstrate the possibility for this strategy in
alkaliphilic haloarchaea for the first time. In a previous study, we developed a
PEG-mediated transformation technique for alkaliphilic haloarchaea that was
deployed in this study to deliver a gene disruption cassette into the model
organism Natrialba magadii. The gene encoding for the well-studied Natrialba
extracellular protease was successfully disrupted by a recombination marker gene,
demonstrating a proof of principle for the usability of homologous recombination
for genomic manipulations in alkaliphilic haloarchaea. Since halo(alkali)philic
Archaea are polyploid, a selection process was applied in order to obtain a
mutant strain containing exclusively disrupted genes. The resulting strain
exhibited no proteolytic activity measurable by an azo-casein assay.
Complementation was able to restore proteolytic activity. The expression pattern
of the Natrialba extracellular protease was different in the complemented strain.
PMID- 26424766
TI - High temperature microbial activity in upper soil layers.
AB - Biomineralization at high temperatures in upper soil layers has been largely
ignored, although desertification and global warming have led to increasing areas
of soils exposed to high temperatures. Recent publications evidenced thermophilic
bacteria ubiquity in soils as viable cells, and their role in nutrient cycling
and seedling development. High temperature events, frequently observed at medium
and low latitudes, locate temporal niches for thermophiles to grow in soils.
There, at temperatures inhibitory for common mesophiles, thermophilic bacteria
could perform biogeochemical reactions important to the soil food web. Nutrient
cycling analyses in soils at medium and low latitudes would benefit from
considering the potential role of thermophiles.
PMID- 26424767
TI - Prevalence and population analysis of Vibrio parahaemolyticus in aquatic products
from South China markets.
AB - Vibrio parahaemolyticus is a common foodborne pathogen in aquatic products. To
investigate the prevalence of Vibrio parahaemolyticus in aquatic products in
South China, 224 samples were collected from markets in four provinces (11
cities) from May 2013 to January 2014. One hundred and fifty isolates were
isolated from 98 samples. All isolates were analyzed for the presence of
thermostable direct haemolysin (TDH) and TDH-related haemolysin (TRH) by PCR,
antibiotic susceptibility analysis by disk diffusion method, serotyping by
multiplex PCR and molecular typing by enterobacterial repetitive intergenic
consensus sequence PCR (ERIC-PCR) typing. Although all 150 isolates were negative
for tdh, 61 strains were trh positive (40.67%). Antimicrobial susceptibility
results indicated that most strains were resistant to streptomycin (88.67%),
cefazolin (66.00%) and ampicillin (62.67%). All strains were susceptible to
chloramphenicol. Forty percent of all isolates were O2 type. The 150 isolates
were grouped into three clusters by ERIC-PCR typing. The results demonstrated the
presence of V. parahaemolyticus in aquatic products from the retail market and
this methodology can be used for microbiological risk assessment in China.
PMID- 26424768
TI - Revisiting bacterial cyclic nucleotide phosphodiesterases: cyclic AMP hydrolysis
and beyond.
AB - Cyclic-3',5'-adenosine monophosphate (cAMP) is a universal second messenger that
regulates vital activities in bacteria and eukaryotes. Enzymes that hydrolyze
cAMP, called phosphodiesterases (PDEs), negatively regulate the levels of this
messenger molecule and are therefore crucial for signal 'termination'. In this
minireview, I shall summarize the available literature on bacterial cAMP-PDEs,
with particular emphasis on enzymes belonging to the ubiquitously encoded Class
III PDE family exemplified by CpdA from Escherichia coli and Rv0805 from
Mycobacterium tuberculosis. Using available biochemical, structural and
biological information, I shall make a case for re-examining the functions of
these enzymes as merely regulators of intrabacterial cAMP levels and suggest that
some members of this class may have evolved cAMP-independent functions as well.
Finally, I shall highlight the major lacunae in our understanding of these
enzymes and present unanswered questions in the area.
PMID- 26424769
TI - Urinary uroplakin expression in cyclophosphamide-induced rat cystitis model.
AB - Cyclophosphamide (CYP) induces urothelial injury and causes excretion of cellular
exudates at 24 h, followed by rapid restoration at 72 h. We investigated the role
of urinary uroplakin II (UPII) levels in a CYP-induced cystitis model. For the
purpose of this study, 10 controls and 26 CYP-injected female Sprague Dawley rats
were killed at 24 h and 72 h postinjection. The vesical weight, severity of
hematuria, and expression of UPII in the urinary bladder and urine were measured.
CYP decreased the level of vesical UPII messenger RNA at 24 h, followed by rapid
recovery at 72 h. Contrary to the negligible levels of urinary UPII and hematuria
in controls, CYP treatment abruptly increased the excretion of urinary UPII at 24
h. The excretion had subsided at 72 h. Similarly, severe hematuria was observed
at 24 h, with improvement at 72 h. However, some rats still exhibited hematuria
at 72 h. CYP caused increase in vesical weight. The vesical weight at 24 h after
CYP injection was negatively correlated with the vesical UPII level. Rats with
significant hematuria demonstrated higher urinary UPII levels than those with
insignificant hematuria. Vesical UPII could be an important barrier for early CYP
related injury, while the levels of urinary UPII may be associated with the
severity of hematuria during dynamic periods in the urothelium.
PMID- 26424770
TI - Effect of agmatine on experimental vascular endothelial dysfunction.
AB - This study was designed to investigate the effect of agmatine sulfate (AG,
CAS2482-00-0) in nicotine (NIC)-induced vascular endothelial dysfunction (VED) in
rabbits. NIC was administered to produce VED in rabbits with or without AG for 6
weeks. Serum lipid profile, serum thiobarbituric acid reactive substances,
reduced glutathione, superoxide dismutase generation, serum nitrite/nitrate,
serum vascular cellular adhesion molecule-1 (VCAM-1), and aortic nuclear factor
kappaB (NF-kappaB) levels were analyzed.Treatment with AG markedly improves lipid
profile and prevented NIC-induced VED and oxidative stress. The mechanism of AG
in improving NIC-induced VED may be due to the significant reduction in serum
VCAM-1 levels and aortic NF-kappaB. Thus, it may be concluded that AG reduces the
oxidative stress, nitric oxide production, VCAM-1 levels, and aortic NF-kappaB
expression, thereby consequently improving the integrity of vascular endothelium.
PMID- 26424771
TI - Disturbance of autophagic pathway may be involved in the diabetes-induced
oxidative response in brain.
PMID- 26424772
TI - Flavocoxid Protects Against Cadmium-Induced Disruption of the Blood-Testis
Barrier and Improves Testicular Damage and Germ Cell Impairment in Mice
[corrected].
AB - Cadmium (Cd) causes male infertility. There is the need to identify safe
treatments counteracting this toxicity. Flavocoxid is a flavonoid that induces a
balanced inhibition of cyclooxygenase (COX)-1 and COX-2 peroxidase moieties and
of 5-lipoxygenase (LOX) and has efficacy in the male genitourinary system. We
investigated flavocoxid effects on Cd-induced testicular toxicity in mice. Swiss
mice were divided into 4 groups: 2 control groups received 0.9% NaCl (vehicle; 1
ml/kg/day) or flavocoxid (20 mg/kg/day ip); 2 groups were challenged with cadmium
chloride (CdCl2; 2 mg/kg/day ip) and administered with vehicle or flavocoxid. The
treatment lasted for 1 or 2 weeks. The testes were processed for biochemical and
morphological studies. CdCl2 increased phosphorylated extracellular signal
regulated kinase (p-ERK) 1/2, tumor necrosis factor (TNF)-alpha, COX-2, 5-LOX,
malondialdehyde (MDA), B-cell-lymphoma (Bcl)-2-associated X protein (Bax),
follicle-stimulating hormone (FSH), luteinizing hormone (LH), transforming growth
factor (TGF) -beta3, decreased Bcl-2, testosterone, inhibin-B, occludin, N
Cadherin, induced structural damages in the testis and disrupted the blood-testis
barrier. Many TUNEL-positive germ cells and changes in claudin-11, occludin, and
N-cadherin localization were present. Flavocoxid administration reduced, in a
time-dependent way, p-ERK 1/2, TNF-alpha, COX-2, 5-LOX, MDA, Bax, FSH, LH, TGF
beta3, augmented Bcl-2, testosterone, inhibin B, occludin, N-Cadherin, and
improved the structural organization of the testis and the blood-testis barrier.
Few TUNEL-positive germ cells were present and a morphological retrieval of the
intercellular junctions was observed. In conclusion, flavocoxid has a protective
anti-inflammatory, antioxidant, and antiapoptotic function against Cd-induced
toxicity in mice testis. We suggest that flavocoxid may play a relevant positive
role against environmental levels of Cd, otherwise deleterious to gametogenesis
and tubular integrity.
PMID- 26424773
TI - Acute and Long-Term Effects of Brief Sevoflurane Anesthesia During the Early
Postnatal Period in Rats.
AB - The possibility that exposure to general anesthetics during early life results in
long-term impairment of neural function attracted considerable interest over the
past decade. Extensive laboratory data suggest that administration of these drugs
during critical stages of central nervous system development can lead to cell
death, impaired neurogenesis, and synaptic growth as well as cognitive deficits.
These observations are corroborated by several recent human epidemiological
studies arguing that such cognitive impairment might also occur in humans.
Despite the potential public health importance of this issue, several important
questions remain open. Amongst them, how the duration of anesthesia exposure
impact on outcome is as yet not fully elucidated. To gain insight into this
question, here we focused on the short- and long-term impact of a 30-min-long
exposure to clinically relevant concentrations of sevoflurane in rat pups at 2
functionally distinct stages of the brain growth spurt. We show that this
treatment paradigm induced developmental stage-dependent and brain region
specific acute but not lasting changes in dendritic spine densities.
Electrophysiological recordings in hippocampal brain slices from adult animals
exposed to anesthesia in the early postnatal period revealed larger paired-pulse
facilitation but no changes in the long-term potentiation paradigm when compared
with nonanesthetized controls. 5-bromo-2-deoxyuridine pulse and pulse-chase
experiments demonstrated that neither proliferation nor differentiation and
survival of hippocampal progenitors were affected by sevoflurane exposure. In
addition, behavioral testing of short- and long-term memory showed no differences
between control and sevoflurane-exposed animals. Overall, these results suggest
that brief sevoflurane exposure during critical periods of early postnatal
development, although it does not seem to exert major long-term effects on brain
circuitry development, can induce subtle changes in synaptic plasticity and spine
density of which the physiological significance remains to be determined.
PMID- 26424774
TI - Therapeutic Potential and Critical Analysis of the PCSK9 Monoclonal Antibodies
Evolocumab and Alirocumab.
AB - OBJECTIVE: To review the mechanism of action for PCSK9 monoclonal antibodies and
critically evaluate the therapeutic potential of evolocumab and alirocumab in the
treatment of hypercholesterolemia. DATA SOURCES: Ovid MEDLINE search from 1980 to
August 2015 using the terms PCSK9, evolocumab, and alirocumab with forward and
backward citation tracking. STUDY SELECTION AND DATA EXTRACTION: English-language
trials and studies assessing the mechanism, efficacy, or safety of PCSK9
monoclonal antibodies were included. DATA SYNTHESIS: PCSK9 monoclonal antibodies
have a potent ability to reduce low-density lipoprotein (LDL) by almost 50% in
controlled trials: -47.49% (95% CI = -69.6% to -25.4%). They have an acceptable
safety profile with no significant elevations in Creatine Kinase (CK) (odds ratio
[OR] = 0.72; 95% CI = 0.54 to 0.96) or serious adverse events (OR = 1.01; 95% CI
= 0.87 to 1.18), and preliminary evidence suggests reductions in myocardial
infarction (OR = 0.49; 95% CI = 0.26 to 0.93). Although it is effective in
several familial hypercholesterolemia (FH) patient types, it does not work in
homozygous patients with dual allele LDL receptor negative polymorphisms or those
who are homozygous for autosomal recessive hypercholesterolemia. CONCLUSIONS:
Although not preferred over statins because of limited clinical trial evidence of
cardiovascular event reductions, dosing convenience, and expense, PCSK9
monoclonal antibodies will have a prominent role to play in the treatment of
hypercholesterolemia, especially in patients needing large LDL reductions,
including patients with many types of FH.
PMID- 26424775
TI - Influence of Input Hardware and Work Surface Angle on Upper Limb Posture in a
Hybrid Computer Workstation.
AB - OBJECTIVE: We evaluated the effect of work surface angle and input hardware on
upper-limb posture when using a hybrid computer workstation. BACKGROUND: Offices
use sit-stand and/or tablet workstations to increase worker mobility. These
workstations may have negative effects on upper-limb joints by increasing time
spent in non-neutral postures, but a hybrid standing workstation may improve
working postures. METHOD: Fourteen participants completed office tasks in four
workstation configurations: a horizontal or sloped 15 degrees working surface
with computer or tablet hardware. Three-dimensional right upper-limb postures
were recorded during three tasks: reading, form filling, and writing e-mails.
Amplitude probability distribution functions determined the median and range of
upper-limb postures. RESULTS: The sloped-surface tablet workstation decreased
wrist ulnar deviation by 5 degrees when compared to the horizontal-surface
computer when reading. When using computer input devices (keyboard and mouse),
the shoulder, elbow, and wrist were closest to neutral joint postures when
working on a horizontal work surface. The elbow was 23 degrees and 15 degrees
more extended, whereas the wrist was 6 degrees less ulnar deviated, when reading
compared to typing forms or e-mails. CONCLUSION: We recommend that the horizontal
surface computer configuration be used for typing and the sloped-surface tablet
configuration be used for intermittent reading tasks in this hybrid workstation.
APPLICATION: Offices with mobile employees could use this workstation for
alternating their upper-extremity postures; however, other aspects of the device
need further investigation.
PMID- 26424776
TI - Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ.
AB - BACKGROUND: Impact of contemporary treatment of pre-invasive breast cancer
(ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined.
We aimed to evaluate national treatment trends for DCIS and to determine their
impact on disease-specific (DSS) and overall survival (OS). METHODS: The
Surveillance, Epidemiology, and End Results (SEER) registry was queried for
patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were
analyzed using Cochran-Armitage trend test. Survival analyses were performed
using inverse probability weights (IPW)-adjusted competing risk analyses for DSS
and Cox proportional hazard regression for OS. All tests performed were two
sided. RESULTS: One hundred twenty-one thousand and eighty DCIS patients were
identified. The greatest proportion of patients was treated with lumpectomy and
radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral
(23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The
rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy
and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher
for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval
[CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI
= 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy
with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%).
CONCLUSIONS: We identified substantial shifts in treatment patterns for DCIS from
1991 to 2010. When outcomes between locoregional treatment options were compared,
we observed greater differences in OS than DSS, likely reflecting both a
prevailing patient selection bias as well as clinically negligible differences in
breast cancer outcomes between groups.
PMID- 26424777
TI - Long-term Realism and Cost-effectiveness: Primary Prevention in Combatting Cancer
and Associated Inequalities Worldwide.
AB - The global figure of 14 million new cancer cases in 2012 is projected to rise to
almost 22 million by 2030, with the burden in low- and middle-income countries
(LMICs) shifting from 59% to 65% of all cancer cases worldwide over this time.
While the overheads of cancer care are set to rapidly increase in all countries
worldwide irrespective of income, the limited resources to treat and manage the
growing number of cancer patients in LMICs threaten national economic
development. Current data collated in the recent second edition of The Cancer
Atlas by the American Cancer Society and International Agency for Research on
Cancer show that a substantial proportion of cancers are preventable and that
prevention is cost-effective. Therefore, cancer control strategies within
countries must prioritize primary and secondary prevention, alongside cancer
management and palliative care and integrate these measures into existing health
care plans. There are many examples of the effectiveness of prevention in terms
of declining cancer rates and major risk factors, including an 80% decrease in
liver cancer incidence rates among children and young adults following universal
infant hepatitis B vaccination in Taiwan and a 46% reduction in smoking
prevalence in Brazil after the implementation of a more aggressive tobacco
control program beginning in 1989. Prevention can bring rich dividends in net
savings but actions must be promoted and implemented. The successful approaches
to combatting certain infectious diseases provide a model for implementing cancer
prevention, particularly in LMICs, via the utilization of existing
infrastructures for multiple purposes.
PMID- 26424779
TI - Prevalence and Predictors of Inappropriate Delivery of Palliative Thoracic
Radiotherapy for Metastatic Lung Cancer.
AB - BACKGROUND: High-level evidence has established well-recognized standard
treatment regimens for patients undergoing palliative chest radiotherapy (RT) for
stage IV non-small cell lung cancer (NSCLC), including treating with fewer than
15 fractions of RT, and not delivering concurrent chemoradiation (CRT) because of
its increased toxicity and limited efficacy in the palliative setting. METHODS:
The study included patients in the National Cancer Database from 2004 to 2012
with stage IV lung cancer who received palliative chest radiation therapy.
Logistic regression was performed to determine predictors of standard vs
nonstandard regimens (>15 fractions or CRT). All statistical tests were two
sided. RESULTS: There were 46 803 patients in the analysis and 49% received
radiotherapy for longer than 15 fractions, and 28% received greater than 25
fractions. Approximately 19% received CRT. The strongest independent predictors
of long-course RT were private insurance (odds ratio [OR] = 1.40 vs uninsured,
95% confidence interval [CI] = 1.28 to 1.53) and treatment in community cancer
programs (OR = 1.49, 95% CI = 1.38 to 1.58) compared with academic research
programs. The strongest factors that predicted for concurrent chemoradiotherapy
were private insurance (OR = 1.38 95% CI = 1.23 to 1.54) compared with uninsured
patients and treatment in community cancer programs (OR = 1.44, 95% CI = 1.33 to
1.56) compared with academic programs. CONCLUSIONS: Approximately half of all
patients with metastatic lung cancer received a higher number of radiation
fractions than recommended. Patients with private insurance and treated in
community cancer centers were more likely to receive longer courses of RT or CRT.
This demonstrates that a substantial number of patients requiring palliative
thoracic radiotherapy are overtreated and further work is necessary to ensure
these patients are treated according to evidenced-based guidelines.
PMID- 26424778
TI - Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic
Review and Meta-Analysis.
AB - BACKGROUND: Overweight and obesity are associated with breast cancer mortality.
However, the relationship between postdiagnosis weight gain and mortality is
unclear. We conducted a systematic review and meta-analysis of weight gain after
breast cancer diagnosis and breast cancer-specific, all-cause mortality and
recurrence outcomes. METHODS: Electronic databases identified articles up through
December 2014, including: PubMed (1966-present), EMBASE (1974-present), CINAHL
(1982-present), and Web of Science. Language and publication status were
unrestricted. Cohort studies and clinical trials measuring weight change after
diagnosis and all-cause/breast cancer-specific mortality or recurrence were
considered. Participants were women age 18 years or older with stage I-IIIC
breast cancer. Fixed effects analysis summarized the association between weight
gain (>=5.0% body weight) and all-cause mortality; all tests were two-sided.
RESULTS: Twelve studies (n = 23 832) were included. Weight gain (>=5.0%) compared
with maintenance (<+/-5.0%) was associated with increased all-cause mortality
(hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.03 to 1.22, P = .01,
I(2) = 55.0%). Higher risk of mortality was apparent for weight gain >=10.0% (HR
= 1.23, 95% CI = 1.09 to 1.39, P < .001); 5% to 10.0% weight gain was not
associated with all-cause mortality (P = .40). The association was not
statistically significant for those with a prediagnosis body mass index (BMI) of
less than 25 kg/m(2) (HR = 1.14, 95% CI = 0.99 to 1.31, P = .07) or with a BMI of
25 kg/m(2) or higher (HR = 1.00, 95% CI = 0.86 to 1.16, P = .19). Weight gain of
10.0% or more was not associated with hazard of breast cancer-specific mortality
(HR = 1.17, 95% CI = 1.00 to 1.38, P = .05). CONCLUSIONS: Weight gain after
diagnosis of breast cancer is associated with higher all-cause mortality rates
compared with maintaining body weight. Adverse effects are greater for weight
gains of 10.0% or higher.
PMID- 26424780
TI - Addressing Overtreatment in DCIS: What Should Physicians Do Now?
PMID- 26424781
TI - Tinnitus Annoyance in Normal-Hearing Individuals: Correlation With Depression and
Anxiety.
AB - OBJECTIVE: To assess and correlate tinnitus annoyance in normal-hearing patients
with auditory brainstem response and with anxiety/depression. METHODS: A sample
of 84 individuals with tinnitus and normal hearing levels (pure-tone thresholds
<=25 dB HL) was compared to a matched control group of 47 normal-hearing
individuals without tinnitus. All participants underwent auditory brainstem
response testing. Tinnitus annoyance was assessed using the Tinnitus Handicap
Inventory and depression and anxiety using the Beck Depression Inventory and Beck
Anxiety Inventory, respectively. We compared auditory brainstem response and
anxiety/depression symptoms between groups. In the study group, we correlated the
degree of tinnitus annoyance with normal/abnormal auditory brainstem response and
presence/level of anxiety/depression symptoms. RESULTS: All controls had normal
auditory brainstem response; 30 patients with tinnitus had abnormal results.
Thirty-five patients with tinnitus had depression and 41 anxiety, while only 2
controls had depression and none had anxiety, with a significant between-group
difference (P < .001). Normal/abnormal auditory brainstem response showed no
association with tinnitus annoyance, anxiety, or depression. A higher degree of
tinnitus annoyance was associated with severity of depression and anxiety.
CONCLUSIONS: Increased tinnitus annoyance was positively correlated with greater
severity of anxiety and depression in normal-hearing patients but was unrelated
to normal/abnormal auditory brainstem response.
PMID- 26424782
TI - Intraspecific variation in stomatal traits, leaf traits and physiology reflects
adaptation along aridity gradients in a South African shrub.
AB - BACKGROUND AND AIMS: Trait-environment relationships are commonly interpreted as
evidence for local adaptation in plants. However, even when selection analyses
support this interpretation, the mechanisms underlying differential benefits are
often unknown. This study addresses this gap in knowledge using the broadly
distributed South African shrub Protea repens. Specifically, the study examines
whether broad-scale patterns of trait variation are consistent with spatial
differences in selection and ecophysiology in the wild. METHODS: In a common
garden study of plants sourced from 19 populations, associations were measured
between five morphological traits and three axes describing source climates.
Trait-trait and trait-environment associations were analysed in a multi-response
model. Within two focal populations in the wild, selection and path analyses were
used to test associations between traits, fecundity and physiological
performance. KEY RESULTS: Across 19 populations in a common garden, stomatal
density increased with the source population's mean annual temperature and
decreased with its average amount of rainfall in midsummer. Concordantly,
selection analysis in two natural populations revealed positive selection on
stomatal density at the hotter, drier site, while failing to detect selection at
the cooler, moister site. Dry-site plants with high stomatal density also had
higher stomatal conductances, cooler leaf temperatures and higher light-saturated
photosynthetic rates than those with low stomatal density, but no such
relationships were present among wet-site plants. Leaf area, stomatal pore index
and specific leaf area in the garden also co-varied with climate, but within
population differences were not associated with fitness in either wild
population. CONCLUSIONS: The parallel patterns of broad-scale variation,
differences in selection and differences in trait-ecophysiology relationships
suggest a mechanism for adaptive differentiation in stomatal density. Densely
packed stomata may improve performance by increasing transpiration and cooling,
but predominately in drier, hotter climates. This study uniquely shows context
dependent benefits of stomatal density--a trait rarely linked to local adaptation
in plants.
PMID- 26424783
TI - Phylogeography and modes of reproduction in diploid and tetraploid halophytes of
Limonium species (Plumbaginaceae): evidence for a pattern of geographical
parthenogenesis.
AB - BACKGROUND AND AIMS: The genus Limonium (Plumbaginaceae) has long been recognized
to have sexual and apomictic (asexual seed formation) modes of reproduction. This
study aimed to elucidate phylogeographical patterns and modes of reproduction in
diploid and tetraploid Limonium species, namely three putative sexual diploid
species with morphological affinities (L. nydeggeri, L. ovalifolium, L.
lanceolatum) and three related, probably apomict tetraploid species (L.
binervosum, L. dodartii, L. multiflorum). METHODS: cpDNA diversity and
differentiation between natural populations of the species were investigated
using two chloroplast sequence regions (trnL intron and trnL-trnF intergenic
spacer). Floral heteromorphies, ovule cytoembryological analyses and pollination
and crossing tests were performed in representative species of each ploidy group,
namely diploid L. ovalifolium and tetraploid L. multiflorum, using plants from
greenhouse collections. KEY RESULTS AND CONCLUSIONS: Genetic analyses showed that
diploid species have a higher haplotype diversity and a higher number of unique
(endemic) haplotypes than tetraploid species. Network analysis revealed
correlations between cpDNA haplotype distribution and ploidy groups, species
groups and geographical origin, and haplotype sharing within and among species
with distinct ploidy levels. Reproductive biology analyses showed that diploid L.
ovalifolium mainly forms meiotically reduced tetrasporic embryo sacs of Gagea
ova, Adoxa and Drusa types. Limonium multiflorum, however, has only unreduced,
diplosporic (apomictic) embryo sacs of Rudbeckia type, and autonomous apomictic
development seems to occur. Taken together, the findings provide evidence of a
pattern of 'geographical parthenogenesis' in which quaternary climatic
oscillations appear to be involved in the geographical patterns of coastal
diploid and tetraploid Limonium species.
PMID- 26424784
TI - Lower plasticity exhibited by high- versus mid-elevation species in their
phenological responses to manipulated temperature and drought.
AB - BACKGROUND AND AIMS: Recent global changes, particularly warming and drought,
have had worldwide repercussions on the timing of flowering events for many plant
species. Phenological shifts have also been reported in alpine environments,
where short growing seasons and low temperatures make reproduction particularly
challenging, requiring fine-tuning to environmental cues. However, it remains
unclear if species from such habitats, with their specific adaptations, harbour
the same potential for phenological plasticity as species from less demanding
habitats. METHODS: Fourteen congeneric species pairs originating from mid and
high elevation were reciprocally transplanted to common gardens at 1050 and 2000
m a.s.l. that mimic prospective climates and natural field conditions. A drought
treatment was implemented to assess the combined effects of temperature and
precipitation changes on the onset and duration of reproductive phenophases. A
phenotypic plasticity index was calculated to evaluate if mid- and high-elevation
species harbour the same potential for plasticity in reproductive phenology. KEY
RESULTS: Transplantations resulted in considerable shifts in reproductive
phenology, with highly advanced initiation and shortened phenophases at the lower
(and warmer) site for both mid- and high-elevation species. Drought stress
amplified these responses and induced even further advances and shortening of
phenophases, a response consistent with an 'escape strategy'. The observed
phenological shifts were generally smaller in number of days for high-elevation
species and resulted in a smaller phenotypic plasticity index, relative to their
mid-elevation congeners. CONCLUSIONS: While mid- and high-elevation species seem
to adequately shift their reproductive phenology to track ongoing climate
changes, high-elevation species were less capable of doing so and appeared more
genetically constrained to their specific adaptations to an extreme environment
(i.e. a short, cold growing season).
PMID- 26424785
TI - Optimizing tiller production and survival for grain yield improvement in a bread
wheat * spelt mapping population.
AB - BACKGROUND AND AIMS: Tiller production and survival determine final spike number,
and play key roles in grain yield formation in wheat (Triticum aestivum). This
study aimed to understand the genetic and physiological basis of the tillering
process, and its trade-offs with other yield components, by introducing genetic
variation in tillering patterns via a mapping population of wheat * spelt
(Triticum spelta). METHODS: The dynamics of tillering and red/far-red ratio
(R:FR) at the base of a canopy arising from neighbouring plants in a bread wheat
(Triticum aestivum 'Forno') * spelt (Triticum spelta 'Oberkulmer') mapping
population were measured in the field in two growing seasons. Additional thinning
and shading experiments were conducted in the field and glasshouse, respectively.
Yield components were analysed for all experiments, followed by identification of
quantitative trait loci (QTL) associated with each trait. KEY RESULTS: Large
genetic variation in tillering was observed, and more fertile shoots per plant
were associated with more total shoots initiated, faster tillering rate, delayed
tillering onset and cessation, and higher shoot survival. A total of 34 QTL for
tillering traits were identified, and analysis of allelic effects confirmed the
above associations. Low R:FR was associated with early tillering cessation, few
total shoots, high infertile shoot number and shoot abortion, and these results
concurred with the thinning and shading experiments. These effects probably
resulted from an assimilate shortage for tiller buds or developing tillers, due
to early stem elongation and enhanced stem growth induced by low R:FR. More
fertile tillers normally contributed to plant yield and grain number without
reducing yield and grain set of individual shoots. However, there was a decrease
in grain weight, partly because of smaller carpels and fewer stem water-soluble
carbohydrates at anthesis caused by pleiotropy or tight gene linkages.
CONCLUSIONS: Tillering is under the control of both genetic factors and R:FR.
Genetic variation in tillering and tolerance to low R:FR can be used to optimize
tillering patterns for yield improvement in wheat.
PMID- 26424787
TI - Persistent pupillary membrane.
PMID- 26424786
TI - G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in
Obesity and Diabetes.
AB - Obesity and diabetes mellitus are the leading causes of renal disease. In this
study, we determined the regulation and role of the G protein-coupled bile acid
receptor TGR5, previously shown to be regulated by high glucose and/or fatty
acids, in obesity-related glomerulopathy (ORG) and diabetic nephropathy (DN).
Treatment of diabetic db/db mice with the selective TGR5 agonist INT-777
decreased proteinuria, podocyte injury, mesangial expansion, fibrosis, and CD68
macrophage infiltration in the kidney. INT-777 also induced renal expression of
master regulators of mitochondrial biogenesis, inhibitors of oxidative stress,
and inducers of fatty acid beta-oxidation, including sirtuin 1 (SIRT1), sirtuin 3
(SIRT3), and Nrf-1. Increased activity of SIRT3 was evidenced by normalization of
the increased acetylation of mitochondrial superoxide dismutase 2 (SOD2) and
isocitrate dehydrogenase 2 (IDH2) observed in untreated db/db mice. Accordingly,
INT-777 decreased mitochondrial H2O2 generation and increased the activity of
SOD2, which associated with decreased urinary levels of H2O2 and thiobarbituric
acid reactive substances. Furthermore, INT-777 decreased renal lipid
accumulation. INT-777 also prevented kidney disease in mice with diet-induced
obesity. In human podocytes cultured with high glucose, INT-777 induced
mitochondrial biogenesis, decreased oxidative stress, and increased fatty acid
beta-oxidation. Compared with normal kidney biopsy specimens, kidney specimens
from patients with established ORG or DN expressed significantly less TGR5 mRNA,
and levels inversely correlated with disease progression. Our results indicate
that TGR5 activation induces mitochondrial biogenesis and prevents renal
oxidative stress and lipid accumulation, establishing a role for TGR5 in
inhibiting kidney disease in obesity and diabetes.
PMID- 26424788
TI - The clinical, occupational and financial outcomes associated with a bespoke
specialist clinic for military aircrew-a cohort study.
AB - OBJECTIVES: To assess the clinical, occupational and financial outcomes of a new
Clinical Aviation Medicine Service (CAMS) for UK military personnel. METHODS:
Consecutive patients over a 2 year period were included. Predictors of flying
restrictions at referral and final outcome following consultation were modelled
using logistic regression. National Health Service (NHS) Payment by Results
tariffs and Defence capitation data were used to assess the financial impact of
the service. RESULTS: Eight hundred and sixteen new referrals (94.5% male, median
age 45 years (range 19-75)) were received and 1025 consultations performed.
Cardiovascular disease was the commonest reason for referral. CAMS clinical
activity cost at NHS tariff was L453 310 representing a saving of L316 173 (L137
137 delivery cost). In total, 310/816 (38%) patients had employment restrictions
on referral and 49.0% of this group returned to full employment following their
initial consultation. Compared with cardiology, general medicine and respiratory
patients were more likely to have been occupationally restricted prior to
referral (50 vs. 35%, OR 1.81; 95% CI 1.18-2.76, P values=0.006 and 53 vs. 35%,
OR 2.12; 95% CI 1.15-3.90, P values = 0.016, respectively). Overall 581/816
(71.2%) of patients returned to unrestricted employment while 98/816 (12.0%) were
unable to continue in any aircrew role. The service saved 7000 lost working days
per year at an estimated occupational saving of ~L1 million per annum.
CONCLUSIONS: This bespoke service has allowed rapid, occupationally relevant
clinical care to be delivered with both time and financial savings. The model may
have significant occupational and financial relevance for other environmental and
occupational medical organizations.
PMID- 26424789
TI - Pulmonary Langerhans Cell Histiocytosis in pre-existing chronic myelomonocytic
leukaemia: a rare association.
PMID- 26424790
TI - Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2.
AB - Epigenetic control of gene expression is critical for normal fetal development.
However, chromatin-related mechanisms that activate bone-specific programs during
osteogenesis have remained underexplored. Therefore, we investigated the
expression profiles of a large cohort of epigenetic regulators (>300) during
osteogenic differentiation of human mesenchymal cells derived from the stromal
vascular fraction of adipose tissue (AMSCs). Molecular analyses establish that
the polycomb group protein EZH2 (enhancer of zeste homolog 2) is down-regulated
during osteoblastic differentiation of AMSCs. Chemical inhibitor and siRNA
knockdown studies show that EZH2, a histone methyltransferase that catalyzes
trimethylation of histone 3 lysine 27 (H3K27me3), suppresses osteogenic
differentiation. Blocking EZH2 activity promotes osteoblast differentiation and
suppresses adipogenic differentiation of AMSCs. High throughput RNA sequence
(mRNASeq) analysis reveals that EZH2 inhibition stimulates cell cycle inhibitory
proteins and enhances the production of extracellular matrix proteins.
Conditional genetic loss of Ezh2 in uncommitted mesenchymal cells (Prrx1-Cre)
results in multiple defects in skeletal patterning and bone formation, including
shortened forelimbs, craniosynostosis, and clinodactyly. Histological analysis
and mRNASeq profiling suggest that these effects are attributable to growth plate
abnormalities and premature cranial suture closure because of precocious
maturation of osteoblasts. We conclude that the epigenetic activity of EZH2 is
required for skeletal patterning and development, but EZH2 expression declines
during terminal osteoblast differentiation and matrix production.
PMID- 26424791
TI - Characterization of the Pseudomonas aeruginosa Glycoside Hydrolase PslG Reveals
That Its Levels Are Critical for Psl Polysaccharide Biosynthesis and Biofilm
Formation.
AB - A key component of colonization, biofilm formation, and protection of the
opportunistic human pathogen Pseudomonas aeruginosa is the biosynthesis of the
exopolysaccharide Psl. Composed of a pentameric repeating unit of mannose,
glucose, and rhamnose, the biosynthesis of Psl is proposed to occur via a Wzx/Wzy
dependent mechanism. Previous genetic studies have shown that the putative
glycoside hydrolase PslG is essential for Psl biosynthesis. To understand the
function of this protein, the apo-structure of the periplasmic domain of PslG
(PslG(31-442)) and its complex with mannose were determined to 2.0 and 1.9 A
resolution, respectively. Despite a domain architecture and positioning of
catalytic residues similar to those of other family 39 glycoside hydrolases,
PslG(31-442) exhibits a unique 32-A-long active site groove that is distinct from
other structurally characterized family members. PslG formed a complex with two
mannose monosaccharides in this groove, consistent with binding data obtained
from intrinsic tryptophan fluorescence. PslG was able to catalyze the hydrolysis
of surface-associated Psl, and this activity was abolished in a E165Q/E276Q
double catalytic variant. Surprisingly, P. aeruginosa variants with these
chromosomal mutations as well as a pslG deletion mutant were still capable of
forming Psl biofilms. However, overexpression of PslG in a pslG deletion
background impaired biofilm formation and resulted in less surface-associated
Psl, suggesting that regulation of this enzyme is important during polysaccharide
biosynthesis.
PMID- 26424792
TI - Reciprocal Phosphorylation and Palmitoylation Control Dopamine Transporter
Kinetics.
AB - The dopamine transporter is a neuronal protein that drives the presynaptic
reuptake of dopamine (DA) and is the major determinant of transmitter
availability in the brain. Dopamine transporter function is regulated by protein
kinase C (PKC) and other signaling pathways through mechanisms that are complex
and poorly understood. Here we investigate the role of Ser-7 phosphorylation and
Cys-580 palmitoylation in mediating steady-state transport kinetics and PKC
stimulated transport down-regulation. Using both mutational and pharmacological
approaches, we demonstrate that these post-translational modifications are
reciprocally regulated, leading to transporter populations that display high
phosphorylation-low palmitoylation or low phosphorylation-high palmitoylation.
The balance between the modifications dictates transport capacity, as conditions
that promote high phosphorylation or low palmitoylation reduce transport Vmax and
enhance PKC-stimulated down-regulation, whereas conditions that promote low
phosphorylation or high palmitoylation increase transport Vmax and suppress PKC
stimulated down-regulation. Transitions between these functional states occur
when endocytosis is blocked or undetectable, indicating that the modifications
kinetically regulate the velocity of surface transporters. These findings reveal
a novel mechanism for control of DA reuptake that may represent a point of
dysregulation in DA imbalance disorders.
PMID- 26424793
TI - DISC1 Protein Regulates gamma-Aminobutyric Acid, Type A (GABAA) Receptor
Trafficking and Inhibitory Synaptic Transmission in Cortical Neurons.
AB - Association studies have suggested that Disrupted-in-Schizophrenia 1 (DISC1)
confers a genetic risk at the level of endophenotypes that underlies many major
mental disorders. Despite the progress in understanding the significance of DISC1
at neural development, the mechanisms underlying DISC1 regulation of synaptic
functions remain elusive. Because alterations in the cortical GABA system have
been strongly linked to the pathophysiology of schizophrenia, one potential
target of DISC1 that is critically involved in the regulation of cognition and
emotion is the GABAA receptor (GABAAR). We found that cellular knockdown of DISC1
significantly reduced GABAAR-mediated synaptic and whole-cell current, whereas
overexpression of wild-type DISC1, but not the C-terminal-truncated DISC1 (a
schizophrenia-related mutant), significantly increased GABAAR currents in
pyramidal neurons of the prefrontal cortex. These effects were accompanied by
DISC1-induced changes in surface GABAAR expression. Moreover, the regulation of
GABAARs by DISC1 knockdown or overexpression depends on the microtubule motor
protein kinesin 1 (KIF5). Our results suggest that DISC1 exerts an important
effect on GABAergic inhibitory transmission by regulating KIF5/microtubule-based
GABAAR trafficking in the cortex. The knowledge gained from this study would shed
light on how DISC1 and the GABA system are linked mechanistically and how their
interactions are critical for maintaining a normal mental state.
PMID- 26424794
TI - The Silent Sway of Splicing by Synonymous Substitutions.
AB - Alternative splicing diversifies mRNA transcripts in human cells. This sequence
driven process can be influenced greatly by mutations, even those that do not
change the protein coding potential of the transcript. Synonymous mutations have
been shown to alter gene expression through modulation of splicing, mRNA
stability, and translation. Using a synonymous position mutation library in SMN1
exon 7, we show that 23% of synonymous mutations across the exon decrease exon
inclusion, suggesting that nucleotide identity across the entire exon has been
evolutionarily optimized to support a particular exon inclusion level. Although
phylogenetic conservation scores are insufficient to identify synonymous
positions important for exon inclusion, an alignment of organisms filtered based
on similar exon/intron architecture is highly successful. Although many of the
splicing neutral mutations are observed to occur, none of the exon inclusion
reducing mutants was found in the filtered alignment. Using the modified
phylogenetic comparison as an approach to evaluate the impact on pre-mRNA
splicing suggests that up to 45% of synonymous SNPs are likely to alter pre-mRNA
splicing. These results demonstrate that coding and pre-mRNA splicing pressures
co-evolve and that a modified phylogenetic comparison based on the exon/intron
architecture is a useful tool in identifying splice altering SNPs.
PMID- 26424795
TI - Homocitrullination Is a Novel Histone H1 Epigenetic Mark Dependent on Aryl
Hydrocarbon Receptor Recruitment of Carbamoyl Phosphate Synthase 1.
AB - The aryl hydrocarbon receptor (AhR), a regulator of xenobiotic toxicity, is a
member of the eukaryotic Per-Arnt-Sim domain protein family of transcription
factors. Recent evidence identified a novel AhR DNA recognition sequence called
the nonconsensus xenobiotic response element (NC-XRE). AhR binding to the NC-XRE
in response to activation by the canonical ligand 2,3,7,8-tetrachlorodibenzo-p
dioxin resulted in concomitant recruitment of carbamoyl phosphate synthase 1
(CPS1) to the NC-XRE. Studies presented here demonstrate that CPS1 is a bona fide
nuclear protein involved in homocitrullination (hcit), including a key lysine
residue on histone H1 (H1K34hcit). H1K34hcit represents a hitherto unknown
epigenetic mark implicated in enhanced gene expression of the peptidylarginine
deiminase 2 gene, itself a chromatin-modifying protein. Collectively, our data
suggest that AhR activation promotes CPS1 recruitment to DNA enhancer sites in
the genome, resulting in a specific enzyme-independent post-translational
modification of the linker histone H1 protein (H1K34hcit), pivotal in altering
local chromatin structure and transcriptional activation.
PMID- 26424796
TI - Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin
2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane.
AB - The melanocortin-2 (MC2) receptor is a G protein-coupled receptor that mediates
responses to ACTH. The MC2 receptor acts in concert with the MC2 receptor
accessory protein (MRAP) that is absolutely required for ACTH binding and
signaling. MRAP has a single transmembrane domain and forms a highly unusual
antiparallel homodimer that is stably associated with MC2 receptors at the plasma
membrane. Despite the physiological importance of the interaction between the MC2
receptor and MRAP, there is little understanding of how the accessory protein
works. The dual topology of MRAP has made it impossible to determine whether
highly conserved and necessary regions of MRAP are required on the intracellular
or extracellular face of the plasma membrane. The strategy used here was to fix
the orientation of two antiparallel MRAP molecules and then introduce
inactivating mutations on one side of the membrane or the other. This was
achieved by engineering proteins containing tandem copies of MRAP fused to the
amino terminus of the MC2 receptor. The data firmly establish that only the
extracellular amino terminus (Nout) copy of MRAP, oriented with critical segments
on the extracellular side of the membrane, is essential. The transmembrane domain
of MRAP is also required in only the Nout orientation. Finally, activity of MRAP
MRAP-MC2-receptor fusion proteins with inactivating mutations in either MRAP or
the receptor was rescued by co-expression of free wild-type MRAP or free wild
type receptor. These results show that the basic MRAP-MRAP-receptor signaling
unit forms higher order complexes and that these multimers signal.
PMID- 26424797
TI - PP2A/B56 and GSK3/Ras suppress PKB activity during Dictyostelium chemotaxis.
AB - We have previously shown that the Dictyostelium protein phosphatase 2A regulatory
subunit B56, encoded by psrA, modulates Dictyostelium cell differentiation
through negatively affecting glycogen synthase kinase 3 (GSK3) function. Our
follow-up research uncovered that B56 preferentially associated with GDP forms of
RasC and RasD, but not with RasG in vitro, and psrA(-) cells displayed
inefficient activation of multiple Ras species, decreased random motility, and
inefficient chemotaxis toward cAMP and folic acid gradient. Surprisingly, psrA(-)
cells displayed aberrantly high basal and poststimulus phosphorylation of
Dictyostelium protein kinase B (PKB) kinase family member PKBR1 and PKB
substrates. Expression of constitutively active Ras mutants or inhibition of GSK3
in psrA(-) cells increased activities of both PKBR1 and PKBA, but only the PKBR1
activity was increased in wild-type cells under the equivalent conditions,
indicating that either B56- or GSK3-mediated suppressive mechanism is sufficient
to maintain low PKBA activity, but both mechanisms are necessary for suppressing
PKBR1. Finally, cells lacking RasD or RasC displayed normal PKBR1 regulation
under GSK3-inhibiting conditions, indicating that RasC or RasD proteins are
essential for GSK3-mediated PKBR1 inhibition. In summary, B56 constitutes
inhibitory circuits for PKBA and PKBR1 and thus heavily affects Dictyostelium
chemotaxis.
PMID- 26424798
TI - Basic mechanism for biorientation of mitotic chromosomes is provided by the
kinetochore geometry and indiscriminate turnover of kinetochore microtubules.
AB - Accuracy of chromosome segregation relies on the ill-understood ability of
mitotic kinetochores to biorient, whereupon each sister kinetochore forms
microtubule (MT) attachments to only one spindle pole. Because initial MT
attachments result from chance encounters with the kinetochores, biorientation
must rely on specific mechanisms to avoid and resolve improper attachments. Here
we use mathematical modeling to critically analyze the error-correction potential
of a simplified biorientation mechanism, which involves the back-to-back
arrangement of sister kinetochores and the marked instability of kinetochore-MT
attachments. We show that a typical mammalian kinetochore operates in a near
optimal regime, in which the back-to-back kinetochore geometry and the
indiscriminate kinetochore-MT turnover provide strong error-correction activity.
In human cells, this mechanism alone can potentially enable normal segregation of
45 out of 46 chromosomes during one mitotic division, corresponding to a mis
segregation rate in the range of 10(-1)-10(-2) per chromosome. This theoretical
upper limit for chromosome segregation accuracy predicted with the basic
mechanism is close to the mis-segregation rate in some cancer cells; however, it
cannot explain the relatively low chromosome loss in diploid human cells,
consistent with their reliance on additional mechanisms.
PMID- 26424799
TI - Spontaneous and electric field-controlled front-rear polarization of human
keratinocytes.
AB - It has long been known that electrical fields (EFs) are able to influence the
direction of migrating cells, a process commonly referred to as electrotaxis or
galvanotaxis. Most studies have focused on migrating cells equipped with an
existing polarity before EF application, making it difficult to delineate EF
specific pathways. Here we study the initial events in front-rear organization of
spreading keratinocytes to dissect the molecular requirements for random and EF
controlled polarization. We find that Arp2/3-dependent protrusive forces and
Rac1/Cdc42 activity were generally required for both forms of polarization but
were dispensable for controlling the direction of EF-controlled polarization. By
contrast, we found a crucial role for extracellular pH as well as G protein
coupled-receptor (GPCR) or purinergic signaling in the control of directionality.
The normal direction of polarization toward the cathode was reverted by lowering
extracellular pH. Polarization toward the anode was also seen at neutral pH when
GPCR or purinergic signaling was inhibited. However, the stepwise increase of
extracellular pH in this scenario led to restoration of cathodal polarization.
Overall our work puts forward a model in which the EF uses distinct polarization
pathways. The cathodal pathway involves GPCR/purinergic signaling and is dominant
over the anodal pathway at neutral pH.
PMID- 26424800
TI - gp78 functions downstream of Hrd1 to promote degradation of misfolded proteins of
the endoplasmic reticulum.
AB - Eukaryotic cells eliminate misfolded proteins from the endoplasmic reticulum (ER)
via a conserved process termed ER-associated degradation (ERAD). Central
regulators of the ERAD system are membrane-bound ubiquitin ligases, which are
thought to channel misfolded proteins through the ER membrane during
retrotranslocation. Hrd1 and gp78 are mammalian ubiquitin ligases homologous to
Hrd1p, an ubiquitin ligase essential for ERAD in Saccharomyces cerevisiae.
However, the functional relevance of these proteins to Hrd1p is unclear. In this
paper, we characterize the gp78-containing ubiquitin ligase complex and define
its functional interplay with Hrd1 using biochemical and recently developed
CRISPR-based genetic tools. Our data show that transient inactivation of the gp78
complex by short hairpin RNA-mediated gene silencing causes significant
stabilization of both luminal and membrane ERAD substrates, but unlike Hrd1,
which plays an essential role in retrotranslocation and ubiquitination of these
ERAD substrates, knockdown of gp78 does not affect either of these processes.
Instead, gp78 appears to act downstream of Hrd1 to promote ERAD via cooperation
with the BAG6 chaperone complex. We conclude that the Hrd1 complex forms an
essential retrotranslocation module that is evolutionarily conserved, but the
mammalian ERAD system uses additional ubiquitin ligases to assist Hrd1 during
retrotranslocation.
PMID- 26424801
TI - Probability-based particle detection that enables threshold-free and robust in
vivo single-molecule tracking.
AB - Single-molecule detection in fluorescence nanoscopy has become a powerful tool in
cell biology but can present vexing issues in image analysis, such as limited
signal, unspecific background, empirically set thresholds, image filtering, and
false-positive detection limiting overall detection efficiency. Here we present a
framework in which expert knowledge and parameter tweaking are replaced with a
probability-based hypothesis test. Our method delivers robust and threshold-free
signal detection with a defined error estimate and improved detection of weaker
signals. The probability value has consequences for downstream data analysis,
such as weighing a series of detections and corresponding probabilities, Bayesian
propagation of probability, or defining metrics in tracking applications. We show
that the method outperforms all current approaches, yielding a detection
efficiency of >70% and a false-positive detection rate of <5% under conditions
down to 17 photons/pixel background and 180 photons/molecule signal, which is
beneficial for any kind of photon-limited application. Examples include limited
brightness and photostability, phototoxicity in live-cell single-molecule
imaging, and use of new labels for nanoscopy. We present simulations,
experimental data, and tracking of low-signal mRNAs in yeast cells.
PMID- 26424802
TI - Reorganization of actin filaments by ADF/cofilin is involved in formation of
microtubule structures during Xenopus oocyte maturation.
AB - We examined the reorganization of actin filaments and microtubules during Xenopus
oocyte maturation. Surrounding the germinal vesicle (GV) in immature oocytes, the
cytoplasmic actin filaments reorganized to accumulate beneath the vegetal side of
the GV, where the microtubule-organizing center and transient microtubule array
(MTOC-TMA) assembled, just before GV breakdown (GVBD). Immediately after GVBD,
both Xenopus ADF/cofilin (XAC) and its phosphatase Slingshot (XSSH) accumulated
into the nuclei and intranuclear actin filaments disassembled from the vegetal
side with the shrinkage of the GV. As the MTOC-TMA developed well, cytoplasmic
actin filaments were retained at the MTOC-TMA base region. Suppression of XAC
dephosphorylation by anti-XSSH antibody injection inhibited both actin filament
reorganization and proper formation and localization of both the MTOC-TMA and
meiotic spindles. Stabilization of actin filaments by phalloidin also inhibited
formation of the MTOC-TMA and disassembly of intranuclear actin filaments without
affecting nuclear shrinkage. Nocodazole also caused the MTOC-TMA and the
cytoplasmic actin filaments at its base region to disappear, which further
impeded disassembly of intranuclear actin filaments from the vegetal side. XAC
appears to reorganize cytoplasmic actin filaments required for precise assembly
of the MTOC and, together with the MTOC-TMA, regulate the intranuclear actin
filament disassembly essential for meiotic spindle formation.
PMID- 26424803
TI - Intraflagellar transport is essential for mammalian spermiogenesis but is absent
in mature sperm.
AB - Drosophila sperm are unusual in that they do not require the intraflagellar
transport (IFT) system for assembly of their flagella. In the mouse, the IFT
proteins are very abundant in testis, but we here show that mature sperm are
completely devoid of them, making the importance of IFT to mammalian sperm
development unclear. To address this question, we characterized spermiogenesis
and fertility in the Ift88(Tg737Rpw) mouse. This mouse has a hypomorphic mutation
in the gene encoding the IFT88 subunit of the IFT particle. This mutation is
highly disruptive to ciliary assembly in other organs. Ift88(-/-) mice are
completely sterile. They produce ~ 350-fold fewer sperm than wild-type mice, and
the remaining sperm completely lack or have very short flagella. The short
flagella rarely have axonemes but assemble ectopic microtubules and outer dense
fibers and accumulate improperly assembled fibrous sheath proteins. Thus IFT is
essential for the formation but not the maintenance of mammalian sperm flagella.
PMID- 26424804
TI - Dual pulse-chase microscopy reveals early divergence in the biosynthetic
trafficking of the Na,K-ATPase and E-cadherin.
AB - Recent evidence indicates that newly synthesized membrane proteins that share the
same distributions in the plasma membranes of polarized epithelial cells can
pursue a variety of distinct trafficking routes as they travel from the Golgi
complex to their common destination at the cell surface. In most polarized
epithelial cells, both the Na,K-ATPase and E-cadherin are localized to the
basolateral domains of the plasma membrane. To examine the itineraries pursued by
newly synthesized Na,K-ATPase and E-cadherin in polarized MDCK epithelial cells,
we used the SNAP and CLIP labeling systems to fluorescently tag temporally
defined cohorts of these proteins and observe their behaviors simultaneously as
they traverse the secretory pathway. These experiments reveal that E-cadherin is
delivered to the cell surface substantially faster than is the Na,K-ATPase.
Furthermore, the surface delivery of newly synthesized E-cadherin to the plasma
membrane was not prevented by the 19 degrees C temperature block that inhibits
the trafficking of most proteins, including the Na,K-ATPase, out of the trans
Golgi network. Consistent with these distinct behaviors, populations of newly
synthesized E-cadherin and Na,K-ATPase become separated from one another within
the trans-Golgi network, suggesting that they are sorted into different carrier
vesicles that mediate their post-Golgi trafficking.
PMID- 26424806
TI - A Comparison of Two Strategies for Building an Exposure Prediction Model.
AB - Cost-efficient assessments of job exposures in large populations may be obtained
from models in which 'true' exposures assessed by expensive measurement methods
are estimated from easily accessible and cheap predictors. Typically, the models
are built on the basis of a validation study comprising 'true' exposure data as
well as an extensive collection of candidate predictors from questionnaires or
company data, which cannot all be included in the models due to restrictions in
the degrees of freedom available for modeling. In these situations, predictors
need to be selected using procedures that can identify the best possible subset
of predictors among the candidates. The present study compares two strategies for
selecting a set of predictor variables. One strategy relies on stepwise
hypothesis testing of associations between predictors and exposure, while the
other uses cluster analysis to reduce the number of predictors without relying on
empirical information about the measured exposure. Both strategies were applied
to the same dataset on biomechanical exposure and candidate predictors among
computer users, and they were compared in terms of identified predictors of
exposure as well as the resulting model fit using bootstrapped resamples of the
original data. The identified predictors were, to a large part, different between
the two strategies, and the initial model fit was better for the stepwise testing
strategy than for the clustering approach. Internal validation of the models
using bootstrap resampling with fixed predictors revealed an equally reduced
model fit in resampled datasets for both strategies. However, when predictor
selection was incorporated in the validation procedure for the stepwise testing
strategy, the model fit was reduced to the extent that both strategies showed
similar model fit. Thus, the two strategies would both be expected to perform
poorly with respect to predicting biomechanical exposure in other samples of
computer users.
PMID- 26424805
TI - Emissions from a Diesel Engine using Fe-based Fuel Additives and a Sintered Metal
Filtration System.
AB - A series of laboratory tests were conducted to assess the effects of Fe
containing fuel additives on aerosols emitted by a diesel engine retrofitted with
a sintered metal filter (SMF) system. Emission measurements performed upstream
and downstream of the SMF system were compared, for cases when the engine was
fueled with neat ultralow sulfur diesel (ULSD) and with ULSD treated with two
formulations of additives containing Fe-based catalysts. The effects were
assessed for four steady-state engine operating conditions and one transient
cycle. The results showed that the SMF system reduced the average total number
and surface area concentrations of aerosols by more than 100-fold. The total mass
and elemental carbon results confirmed that the SMF system was indeed very
effective in the removal of diesel aerosols. When added at the recommended
concentrations (30 p.p.m. of iron), the tested additives had minor adverse
impacts on the number, surface area, and mass concentrations of filter-out (FOut)
aerosols. For one of the test cases, the additives may have contributed to
measurable concentrations of engine-out (EOut) nucleation mode aerosols. The
additives had only a minor impact on the concentration and size distribution of
volatile and semi-volatile FOut aerosols. Metal analysis showed that the
introduction of Fe with the additives substantially increased Fe concentration in
the EOut, but the SMF system was effective in removal of Fe-containing aerosols.
The FOut Fe concentrations for all three tested fuels were found to be much lower
than the corresponding EOut Fe concentrations for the case of untreated ULSD
fuel. The results support recommendations that these additives should not be used
in diesel engines unless they are equipped with exhaust filtration systems. Since
the tested SMF system was found to be very efficient in removing Fe introduced by
the additives, the use of these additives should not result in a measurable
increase in emissions of de novo generated Fe-containing aerosols. The findings
from this study should promote a better understanding of the benefits and
challenges of using sintered metal systems and fuel additives to control the
exposure of underground miners and other workers to diesel aerosols and gases.
PMID- 26424807
TI - Early adolescent Depo-Provera exposure increases stillbirths in adult sooty
mangabeys.
AB - The 3-month injectable contraceptive medroxyprogesterone acetate (MPA; Depo
Provera) is a synthetic progestin that protects against pregnancy by suppressing
ovulation. Studies have focused on the resumption of ovulation after MPA
treatment cessation but neglected potential long-term effects of MPA exposure on
future successful reproduction. MPA is frequently administered to adolescent
girls; however, long-term fertility effects of adolescent MPA exposure have not
been explored. We investigated fertility after extended MPA exposure in a species
of old world primate, the sooty mangabey (Cercocebus atys). Female sooty
mangabeys (n=31) received chronic MPA-treatment for 4-8 years. At MPA-treatment
onset, subjects were either parous adults (n=14) or nulliparous adolescents
(n=17), with adolescent-treated subjects being further divided into those who had
reached first ovulation (n=10) and those who had not (n=7). After MPA-treatment
cessation, adolescent-treated females had a significantly higher incidence of
stillbirth than did age-matched and parity-matched controls, whereas adult
treated females did not differ from their matched controls. Females placed on MPA
treatment prior to first ovulation had a significantly higher incidence of
stillbirth post-treatment than did females placed on MPA-treatment after first
ovulation. Diabetic females had an increased incidence of stillbirth as compared
to nondiabetic females; however, when controlling for diabetes, MPA exposure
prior to first ovulation was still a significant positive predictor of
stillbirth. These findings suggest that the post-treatment fertility effects of
chronic MPA exposure vary with the developmental timing of treatment onset and
raise concern about the use of MPA as a contraceptive for adolescent girls.
PMID- 26424808
TI - Potential role of autophagy in the bactericidal activity of human PMNs for
Bacillus anthracis.
AB - Bacillus anthracis, the causative agent of anthrax, is acquired by mammalian
hosts from the environment, as quiescent endospores. These endospores must
germinate inside host cells, forming vegetative bacilli, before they can express
the virulence factors that enable them to evade host defenses and disseminate
throughout the body. While the role of macrophages and dendritic cells in this
initial interaction has been established, the role of polymorphonuclear
leukocytes (PMNs) has not been adequately defined. We discovered that while B.
anthracis 34F2 Sterne endospores germinate poorly within non-activated human
PMNs, these phagocytes exhibit rapid microbicidal activity toward the outgrown
vegetative bacilli, independent of superoxide and nitric oxide. These findings
suggest that a non-free radical pathway kills B. anthracis bacilli. We also find
in PMNs an autophagic mechanism of bacterial killing based on the rapid induction
of LC-3 conversion, beclin-1 expression, sequestosome 1 (SQSTM1) degradation and
inhibition of bactericidal activity by the inhibitor, 3-methyladenine. These
findings extend to PMNs an autophagic bactericidal mechanism previously described
for other phagocytes.
PMID- 26424809
TI - Factors affecting well-being in adults recently diagnosed with rheumatoid
arthritis.
AB - This article examines role stress, key psychosocial variables, and well-being in
adults recently diagnosed with rheumatoid arthritis. Patients recently diagnosed
with rheumatoid arthritis must often learn to balance disease and role-related
responsibilities. This was cross-sectional, descriptive study ( N = 80). Data
were analyzed using correlation coefficients and linear regression models.
Participants were predominantly female (78%), married, and employed. Mean age and
disease duration were 54.2 years and 24.2 months, respectively. The findings
suggest that well-being is influenced by feelings of being self-efficacious and
having balance in their roles and less to do with social support received from
others.
PMID- 26424810
TI - Exploring gender and identity issues among female adolescent and young adults who
connect in an anonymous platform.
AB - There has been an increased usage of online cancer support groups as a resource
for health-related information and social support. This work analyzes message
blog posts from an anonymous online support community to better understand issues
related to gender and identity among female adolescent and young adults. This
work sheds further light into the nuances of gender and identity issues including
motherhood and reproductive issues, physical appearance, and romantic
relationships. Specifically, findings reveal that female adolescent and young
adults experience issues pertaining to infertility, feeling like a bad mom, hair
loss, scarring, dating, and intimacy. These findings of this work offer further
guidance about how healthcare providers and caregivers can attempt to meet the
needs of female adolescent and young adults.
PMID- 26424811
TI - Anxiety prior to breast biopsy: Relationships with length of time from breast
biopsy recommendation to biopsy procedure and psychosocial factors.
AB - This study investigated how time from breast biopsy recommendation to biopsy
procedure affected pre-biopsy anxiety ( N = 140 women), and whether the
relationship between wait time and anxiety was affected by psychosocial factors
(chronic life stress, traumatic events, social support). Analyses showed a
significant interaction between wait time and chronic life stress. Increased time
from biopsy recommendation was associated with greater anxiety in women with low
levels of life stress. Women with high levels of life stress experienced
increased anxiety regardless of wait time. These results suggest that women may
benefit from shorter wait times and receiving strategies for managing anxiety.
PMID- 26424813
TI - Antiphospholipid syndrome presenting as cerebral venous sinus thrombosis: a case
series and a review.
AB - The cerebral venous sinus system is a rare site for venous thrombosis except in
patients with antiphospholipid syndrome. We describe three patients presenting
with cerebral venous thrombosis in association with other thrombotic sites in two
patients and as an only site in one patient. Antiphospholipid syndrome has varied
clinical manifestations but the defining feature is the persistent presence of
antiphospholipid antibodies. In this report we will review the clinical and
laboratory diagnostic criteria and the management of patients with
antiphospholipid syndrome.
PMID- 26424812
TI - Following the Footsteps of Chlamydial Gene Regulation.
AB - Regulation of gene expression ensures an organism responds to stimuli and
undergoes proper development. Although the regulatory networks in bacteria have
been investigated in model microorganisms, nearly nothing is known about the
evolution and plasticity of these networks in obligate, intracellular bacteria.
The phylum Chlamydiae contains a vast array of host-associated microbes,
including several human pathogens. The Chlamydiae are unique among obligate,
intracellular bacteria as they undergo a complex biphasic developmental cycle in
which large swaths of genes are temporally regulated. Coupled with the low number
of transcription factors, these organisms offer a model to study the evolution of
regulatory networks in intracellular organisms. We provide the first
comprehensive analysis exploring the diversity and evolution of regulatory
networks across the phylum. We utilized a comparative genomics approach to
construct predicted coregulatory networks, which unveiled genus- and family
specific regulatory motifs and architectures, most notably those of virulence
associated genes. Surprisingly, our analysis suggests that few regulatory
components are conserved across the phylum, and those that are conserved are
involved in the exploitation of the intracellular niche. Our study thus lends
insight into a component of chlamydial evolution that has otherwise remained
largely unexplored.
PMID- 26424814
TI - Adverse histological features in malignant colorectal polyps: a contemporary
series of 239 cases.
AB - AIMS: Screening colonoscopy has led to more colorectal carcinomas presenting at
an early stage potentially curable by endoscopic resection. In this study, we
examined the clinical and histological features of a contemporary series of
malignant colorectal polyps (MCPs) with subsequent surgical resection. METHODS:
We conducted a retrospective study on a consecutive series of MCPs from 239
patients, predominantly males (57.7%) with a median age of 66 years, and assessed
histological parameters associated with residual disease on the surgical
specimens. RESULTS: Median MCP size was 18.6 mm, with 23.1% polyps measuring <=10
mm. From the 140 surgical resection specimens, residual disease was identified in
20 cases, including 12 cases with metastatic lymph nodes and/or 9 cases with
residual carcinoma in the large bowel wall. Histological parameters associated
with nodal metastases were greater width and greater depth of the invasive
component (p=0.001 and 0.006, respectively), poor differentiation (p=0.003) and a
cribriform pattern (p=0.01). The risk of nodal metastases was 23.3% if two or
three of these features were identified, while it was 0% and 4.5% if none or one
was present, respectively. A positive margin was not associated with nodal
metastasis and might be adequately treated by local endoscopic resection.
CONCLUSIONS: Surgical resection should be recommended if >=2 of these adverse
histological features are present and may be warranted if one feature is present.
A positive margin may require additional local resection but not necessarily
surgery if no other adverse factors are present.
PMID- 26424815
TI - Curculigo orchioides Gaertn Effectively Ameliorates the Uro- and Nephrotoxicities
Induced by Cyclophosphamide Administration in Experimental Animals.
AB - Background Curculigo orchioides Gaertn is an ancient medicinal plant (Family:
Amaryllidaceae), well known for its immunomodulatory and rejuvenating effects.
Cyclophosphamide (CPA) is an alkylating agent widely used for treating a variety
of human malignancies, but associated with different toxicities too. Our previous
reports regarding the hemoprotective and hepatoprotective effects of the plant
against CPA toxicities provide the background for the present study, which is
designed to analyze the ameliorative effect of the methanolic extract of C
orchioides on the urotoxicity and nephrotoxicity induced by CPA. Methods CPA was
administered to male Swiss albino mice at a single dose of 1.5 mmol/kg body
weight to induce urotoxicity after 5 days of prophylactic treatment with C
orchioides extract (20 mg/kg body weight). Mesna (2-mercaptoethanesulfonate) was
used as a control drug. Serum, tissue, and urine levels of kidney function
markers and antioxidant levels were checked along with the serum cytokine levels.
Results The plant extract was found to be effective in ameliorating the urotoxic
and nephrotoxic side effects of CPA. Upregulation of serum interferon-gamma and
interleukin-2 levels were observed with C orchioides treatment, which was
decreased by CPA administration. Besides these, serum tumor necrosis factor-alpha
level was also downregulated by C orchioides treatment. Conclusion Curculigo
orchioides was found to be effective against the CPA-induced bladder and renal
toxicities by its antioxidant capability and also by regulating the pro
inflammatory cytokine levels.
PMID- 26424817
TI - Pool palms.
PMID- 26424816
TI - AMPK Inhibits the Stimulatory Effects of TGF-beta on Smad2/3 Activity, Cell
Migration, and Epithelial-to-Mesenchymal Transition.
AB - AMP-activated protein kinase (AMPK), an important downstream effector of the
tumor suppressor liver kinase 1 (LKB1) and pharmacologic target of metformin, is
well known to exert a preventive and inhibitory effect on tumorigenesis; however,
its role in cancer progression and metastasis has not been well characterized.
The present study investigates the potential roles of AMPK in inhibiting cancer
cell migration and epithelial-to-mesenchymal transition (EMT) by regulating the
canonical transforming growth factor beta (TGF-beta) signaling pathway, an
important promoting factor for cancer progression. Our results showed that
activation of AMPK by metformin inhibited TGF-beta-induced Smad2/3
phosphorylation in cancer cells in a dose-dependent manner. The effect of
metformin is dependent on the presence of LKB1. A similar effect was obtained by
expressing a constitutive active mutant of AMPKalpha1 subunit, whereas the
expression of a dominant negative mutant of AMPKalpha1 or ablation of AMPKalpha
subunits greatly enhanced TGF-beta stimulation of Smad2/3 phosphorylation. As a
consequence, expression of genes downstream of Smad2/3, including plasminogen
activator inhibitor-1, fibronectin, and connective tissue growth factor, was
suppressed by metformin in a LKB1-dependent fashion. In addition, metformin
blocked TGF-beta-induced inteleukin-6 expression through both LKB1-dependent and
independent mechanisms. Our results also indicate that activation of LKB1/AMPK
inhibits TGF-beta-stimulated cancer cell migration. Finally, TGF-beta induction
of EMT was inhibited by phenformin and enhanced by knockdown of LKB1 expression
with shRNA. Together, our data suggest that AMPK could be a drug target for
controlling cancer progression and metastasis.
PMID- 26424818
TI - Granulomatous-lymphocytic interstitial lung disease and recurrent sinopulmonary
infections in a patient with Good's syndrome.
AB - Good's syndrome is a rare primary immunodeficiency associated with adult thymoma.
Complications are mainly autoimmune manifestations and recurrent infections with
encapsulated bacteria. Only one possible case of combined granulomatous
lymphocytic interstitial lung disease (GL-ILD) and Good's syndrome have been
described earlier, but the patient died at the time of diagnosis. This is the
first case of GL-ILD in Good's syndrome with a successful outcome. We present a
case of a 43-year-old man with GL-ILD, who suffered from recurrent infections of
Haemophilus influenzae and Pneumocystis jirovecii, with 8-year follow-up. After a
thymectomy, he was diagnosed with Good's syndrome and GL-ILD. He was treated with
prophylactic pivampicillin, quinolones and cephalosporins for his recurrent P.
jirovecii and H. influenzae infections, an approach that proved unsuccessful due
to resistance, with relapse after cessation. He was stabilised with oral
diaminodiphenyl-sulfone for P. jirovecii and colistimethate-sodium inhalations
for H. influenzae, which is a new approach to prophylactic treatment.
PMID- 26424819
TI - Transscleral cyclophotocoagulation in refractory acute and chronic angle closure
glaucoma.
AB - Angle closure glaucoma, both acute and chronic, is a major cause of blindness
worldwide. Transscleral cyclophotocoagulation (TSCP) is conventionally undertaken
non-urgently in patients with advanced glaucoma and poor visual potential with
poor control of intraocular pressure (IOP). We describe a case of a patient with
refractory acute angle closure glaucoma and severe pain in whom emergency TSCP
was undertaken 12 h after presentation, reducing the IOP from 68 to 10 mm Hg.
Further, a patient with chronic angle closure glaucoma underwent TSCP, reducing
the IOP from 78 to 14 mm Hg. Both patients consequently underwent uneventful
phacoemulsification cataract surgery with preservation of visual acuity and long
term IOP control. TSCP may achieve prompt IOP control and symptomatic relief in
the acute setting in patients with acute and chronic forms of angle closure
glaucoma refractory to medical therapy. TSCP may reduce the risk of definitive
surgical intervention by temporising phacoemulsification or trabeculectomy
surgery until the IOP is well controlled.
PMID- 26424820
TI - Dysplasia epiphysealis hemimelica of the ankle: a fracture-like rare
developmental disorder.
AB - Dysplasia epiphysealis hemimelica is a rare developmental disorder which affects
the epiphyses. We report a case of the disease located in the ankle joint,
referred to our clinic with the initial misdiagnosis of a Salter-Harris 3 type
fracture of the distal epiphysis of the tibia. After correct diagnosis, the
patient was treated surgically with the excision of the cartilaginous masses.
Taking an accurate medical history and performing adequate imaging studies is
essential in diagnosing and treating this disease. Fracture-like epiphyseal
configurations in patients with no history of injury should raise suspicion of
periarticular developmental disorders.
PMID- 26424821
TI - A case of metastatic adenocarcinoma on a background of penoscrotal extramammary
Paget's disease.
AB - A 77-year-old man presented with a chronic lesion located in the left penoscrotal
area. Apart from pruritus, bleeding and an occasional discharge from this area,
he also reported reduced appetite and weight loss. Examination revealed an
ulcerated skin lesion attached to a firm subcutaneous mass. Wide local excision
of the lesion revealed invasive adenocarcinoma on a background of extramammary
Paget's disease. Staging studies showed disseminated metastatic disease within
the lymph nodes, and liver and bone metastases. He was treated with carboplatin
and paclitaxel chemotherapy initially, but then continued only on Carboplatin
chemotherapy due to side effects from Paclitaxel. Eleven weeks after the start of
his chemotherapy, his restaging imaging showed reduced lymphadenopathy, unchanged
liver metastasis and sclerosis of bone metastasis. With completion of
chemotherapy, repeat imaging showed stable disease. The patient is currently on
follow-up.
PMID- 26424822
TI - Neglected partial denture in the lower oesophagus presenting after 7 days.
AB - Accidental ingestion of a denture is an acute emergency, and the denture is
usually removed on the same day it is discovered. We present a patient who had a
seizure while asleep, during which his denture broke; he accidentally swallowed a
major part of it, which had a clasp attached. He was unaware that he had ingested
the denture, since he was asymptomatic, but he started developing symptoms after
5 days and presented to us on the eighth day of ingestion. With much difficulty,
the impacted section of the denture in the distal oesophagus was removed with the
combined effort of flexible endoscopy and a rigid oesophagoscopy. Post-procedure,
the patient developed mediastinitis, which was managed conservatively; he is
doing well on follow-up.
PMID- 26424823
TI - A painless pelvic wall ectopic pregnancy.
AB - A 38-year-old woman presented with light vaginal bleeding at approximately 8
weeks gestation. Although she initially presented to accident and emergency with
vaginal bleeding and menstrual-like pain, this rapidly settled and both symptoms
resolved over the following days. An initial ultrasound scan revealed an empty
uterus, with no adnexal masses or free fluid. Miscarriage was presumed. However,
following suboptimal beta-human chorionic gonadotropin decline, further
ultrasonography noted a mass next to the right ovary. The patient underwent
laparoscopy, revealing an ectopic pregnancy closely adherent to the peritoneum of
the right pelvic wall. The patient was treated with systemic methotrexate and
responded well. This rare form of ectopic pregnancy has a high maternal morbidity
and mortality, and its optimal management is not definitively decided, due to the
scarcity of the condition and subsequent lack of high-powered data. We present a
case of successful medical management.
PMID- 26424824
TI - An interesting case of an antihypertensive causing post-prostatectomy
incontinence.
AB - A 70-year-old man underwent a laparoscopic radical prostatectomy with
preservation of bladder neck for T3aN0R0 prostate cancer in December 2009,
(Gleason 4+3, negative surgical margin). His postoperative prostate-specific
antigen rose from 0.01 to 0.05 ng/mL over 19 months. He had salvage radiotherapy
in May 2012. Following radiotherapy, his urinary control worsened and he needed
to wear up to four pads per day. He was being considered for an artificial
urinary sphincter placement. He was also taking doxazosin for hypertension, which
was discontinued. After stopping the doxazosin, his urinary control improved and
he did not require any further intervention. Doctors should be aware of the
effect of alpha-blockers on the internal sphincter and the risk of incontinence
in patients post-prostate cancer treatment.
PMID- 26424826
TI - A predictable but life-threatening complication of hydroxyurea in a patient with
sickle cell anaemia: an experience learned from a Jehovah's Witness.
AB - It is well known that hydroxyurea can cause pancytopaenia secondary to bone
marrow suppression, which is reversible with short-term discontinuation of the
therapy. However, it is important to note that bone marrow suppressive effects
caused by hydroxyurea could be easily potentiated in patients with sickle cell
anaemia complicated by chronic kidney disease (CKD). We present a case of a
Jehovah's Witness with sickle cell anaemia, who developed severe bone marrow
suppression due to the combined effects of hydroxyurea and CKD, resulting in a
prolonged recovery period after discontinuation of hydroxyurea.
PMID- 26424825
TI - Intestinal ganglioneuromatosis: an unusual aetiology for occult gastrointestinal
bleeding.
AB - Intestinal ganglioneuromatosis is a rare disorder of the enteric nervous system.
It is often associated with neurofibromatosis type 1 and multiple endocrine
neoplasia type 2b but, more rarely, it can present in a sporadic and isolated
form. A 66-year-old man presented with a 14-year history of iron deficiency
anaemia, with no visible bleeding, requiring occasional blood transfusions.
Haematological causes of anaemia were thoroughly excluded, and conventional
endoscopic and radiological examinations showed no lesions. Capsule enteroscopy
identified an ulcerated stenosis in the small bowel, but the biopsies taken at
balloon enteroscopy were inconclusive. The patient underwent a laparotomy, which
revealed a stiff and ulcerated stenosis in the ileum. Histological analysis
demonstrated the presence of diffuse intestinal ganglioneuromatosis. Three years
after surgery, the patient is asymptomatic, with normal haemoglobin levels. This
case demonstrates an isolated form of intestinal ganglioneuromatosis, with an
atypical presentation, difficult to diagnose despite an exhaustive evaluation.
PMID- 26424827
TI - Renal fibromuscular dysplasia.
PMID- 26424828
TI - Treatment of peritoneal metastases from colorectal cancer.
AB - Peritoneal seedings of a colorectal tumor represent the second most frequent site
of metastasis (after the liver). In the era of 5-fluorouracil (5-FU)-only
chemotherapy, the prognosis was poor for colorectal cancer with peritoneal
metastases. Within the last few years, new chemotherapeutic and targeted agents
have improved the prognosis; however, the response to these treatments seems to
be lower than that for liver metastases. The combination of cytoreductive surgery
and hyperthermic intraperitoneal chemotherapy have further improved both disease
free survival and overall survival. Keeping this in mind, every patient
presenting with peritoneal metastases from colorectal cancer should be evaluated
and receive adequate treatment, if possible in the above-mentioned combination.
This paper reviews recent advancements in the therapy of peritoneal
carcinomatosis.
PMID- 26424830
TI - Insulin-Like Growth Factor-1 Related to Disability Among Older Adults.
AB - BACKGROUND: Disability is a crucial health problem in aging. Identifying a
biological contributory factor would be useful. Serum insulin-like growth factor
1 (IGF-1) plays an important role in the endocrine system and is associated with
frailty. However, there is no consensus about the relationship between IGF-1 and
disability. This study aimed to examine whether IGF-1 related to incident
disability among older adults. METHODS: The study included 4,133 older adults
(mean age, 71.8+/-5.4 years) who were participants in the "Obu Study of Health
Promotion for the Elderly" cohort study. We collected information on demographic
variables, measured gait speed, Mini Mental State Examination score, and serum
IGF-1 at baseline. During follow-up, incident disability was monitored by Long
Term Care Insurance certification. RESULTS: Disability was observed in 212
participants during a mean follow-up duration period of 29.2 months. A log rank
test indicated that lower levels of serum IGF-1 were related to incident
disability (p = .004). A Cox hazard regression showed a lower quartile in IGF-1
related to disability compared with the highest quartile (Q4), even when
adjusting for covariates including gait speed and Mini Mental State Examination
score (Q1: hazard ratio = 1.72, 95% confidence intervals: 1.06-2.81; Q2: hazard
ratio = 1.64, 95% confidence intervals: 0.99-2.71; Q3: hazard ratio = 1.31, 95%
confidence intervals: 0.76-2.25). In the analysis, stratified by sex, there was
also significant relationship between IGF-1 and disability among women, but not
men. CONCLUSIONS: Lower serum IGF-1 was independently related to disability among
older adults.
PMID- 26424829
TI - Budding off: bringing functional genomics to Candida albicans.
AB - Candida species are the most prevalent human fungal pathogens, with Candida
albicans being the most clinically relevant species. Candida albicans resides as
a commensal of the human gastrointestinal tract but is a frequent cause of
opportunistic mucosal and systemic infections. Investigation of C. albicans
virulence has traditionally relied on candidate gene approaches, but recent
advances in functional genomics have now facilitated global, unbiased studies of
gene function. Such studies include comparative genomics (both between and within
Candida species), analysis of total RNA expression, and regulation and
delineation of protein-DNA interactions. Additionally, large collections of
mutant strains have begun to aid systematic screening of clinically relevant
phenotypes. Here, we will highlight the development of functional genomics in C.
albicans and discuss the use of these approaches to addressing both commensalism
and pathogenesis in this species.
PMID- 26424831
TI - Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected
Mothers in Malawi.
AB - Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers
in resource-limited settings. We examined the prevalence and timing of infant CMV
infection during the first year of life using IgG antibody and avidity among HIV
exposed infants in Malawi and correlated the results with the presence of
detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition
(BAN) study randomized 2,369 mothers and their infants to maternal
antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding,
followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody
avidity from a random subset of infants who had been previously tested with blood
CMV PCR and had available specimens at birth and at 24 and 48 weeks of age.
Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low
or intermediate avidity, signifying primary CMV infections. An additional 22
infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their
blood, indicating infant infections. Taken together, these results show that the
estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age,
81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity.
The CMV serology and avidity testing, combined with the PCR results, confirmed a
high rate of primary CMV infection by 6 months of life among breastfeeding
infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all,
infant CMV infections.
PMID- 26424832
TI - Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks
on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB
4C Vaccine.
AB - In 2013 and 2014, two U.S. universities had meningococcal serogroup B outbreaks
(a total of 14 cases) caused by strains from two different clonal complexes. To
control the outbreaks, students were immunized with a serogroup B meningococcal
vaccine (Novartis) that was not yet licensed in the United States. The vaccine
(referred to as MenB-4C) contains four components capable of eliciting
bactericidal activity. Both outbreak strains had high expression levels of two of
the vaccine antigens (subfamily B factor H binding protein [FHbp] and neisserial
heparin binding antigen [NHba]); the university B outbreak strain also had
moderate expression of a third antigen, NadA. We investigated the bactericidal
activity of sera from mice immunized with FHbp, NHba, or NadA and sera from MenB
4C-immunized infant macaques and an adult human. The postimmunization
bactericidal activity of the macaque or human serum against isolates from
university B with FHbp identification (ID) 1 that exactly matched the vaccine
FHbp sequence variant was 8- to 21-fold higher than that against isolates from
university A with FHbp ID 276 (96% identity to the vaccine antigen). Based on the
bactericidal activity of mouse antisera to FHbp, NadA, or NHba and macaque or
human postimmunization serum that had been depleted of anti-FHbp antibody, the
bactericidal activity against both outbreak strains largely or entirely resulted
from antibodies to FHbp. Thus, despite the high level of strain expression of
FHbp from a subfamily that matched the vaccine antigen, there can be large
differences in anti-FHbp bactericidal activity induced by MenB-4C vaccination.
Further, strains with moderate to high NadA and/or NHba expression can be
resistant to anti-NadA or anti-NHba bactericidal activity elicited by MenB-4C
vaccination.
PMID- 26424834
TI - Vasculopathy-related clinical and pathological features are associated with
severe juvenile dermatomyositis.
AB - OBJECTIVE: Outcome of JDM is highly heterogeneous. Our objective was to determine
clinical and muscle biopsy features associated with poor outcome and response to
treatment. METHODS: Clinical data and muscle biopsy were obtained from a
monocentric cohort of 29 patients. Clinical subgroups were defined by latent
class model analysis of initial and follow-up parameters. Myopathological
features were analysed using validated scores. Capillary loss was determined on
reconstructions of transversal sections and assessed in the different age groups
to take into account variations of muscle capillarization during post-natal
development. Regression models were used to identify initial predictors of
therapeutic response. RESULTS: Two distinct homogeneous subgroups of patients
were identified according to clinical severity and pathological findings. The
smallest group of patients (7/29) presented with severe JDM. Compared with the
other group (22/29), patients had more severe muscle weakness at disease onset,
low remission rate at 12 months, frequent subcutaneous limb oedema or
gastrointestinal (GI) involvement and higher myopathological scores (capillary
dropout, perifascicular necrosis/regeneration, fibres with internal myonuclei and
fibrosis subscores). Relevance of capillary dropout to JDM severity was
substantiated by age-based analysis, confirming its major role in JDM
pathophysiology. Most of these manifestations could be related to vasculopathy
(limb oedema, GI involvement, capillary dropout). Furthermore, Childhood Myositis
Assessment Scale <34 with either GI involvement or muscle endomysial fibrosis at
disease onset were the best predictors of poor response to treatment. CONCLUSION:
Vasculopathy is prominent in severe JDM. Simple criteria can be used at initial
evaluation to identify patients requiring a more intensive therapy.
PMID- 26424833
TI - Perceived Control Moderates the Effects of Functional Limitation on Older Adults'
Social Activity: Findings From the Australian Longitudinal Study of Ageing.
AB - Objectives: Research has shown that functional limitation is related to reduced
social activity in older adults; however, individuals with high perceived control
have greater confidence in their ability to achieve outcomes and are more likely
to show persistence and employ strategies to overcome challenges. The aim of this
study was to examine whether perceived control protects against the negative
effects of functional limitation on older adults' social activity. Method:
Participants were 835 older adults aged 69 to 103 years at baseline from the
Australian Longitudinal Study of Ageing. Multilevel modeling was used to examine
baseline and within-person change in functional limitation and perceived control
as predictors of 18-year trajectories of social activity. Results: An interaction
between baseline functional limitation and perceived control indicated that
having greater functional limitation was associated with less social activity and
greater decline over time for those with lower perceived control, but not for
those with higher control. Within-person change in functional limitation was not
reliably associated with social activity. Discussion: This study highlights the
importance of perceived control as a protective psychological resource and may
have implications for developing interventions aimed at enabling older adults to
maintain their social activity as they experience functional decline.
PMID- 26424835
TI - Risk of myocardial infarction and ischaemic stroke in adults with polymyositis
and dermatomyositis: a general population-based study.
AB - OBJECTIVE: Limited data are available on the risk of cardiovascular disease in DM
and PM. The purpose of this study was to estimate the risk of incident myocardial
infarction (MI) and ischaemic stroke in adults with incident PM/DM at the general
population level. METHODS: We assembled a retrospective cohort of all adults with
incident PM/DM in British Columbia, and we matched up to 10 adults randomly
selected from the general population. We estimated the incidence rates (IRs) per
1000 person-years for MI and stroke. We calculated hazard ratios (HRs), adjusting
for potential confounders. RESULTS: Among 774 new cases of inflammatory
myopathies, 424 had PM (59% female, mean age 60 years) and 350 had DM (65%
female, mean age 56 years). IRs for MI and stroke in PM were 22.52 and 10.15
events per 1000 person-years, respectively, vs 5.50 and 5.58 events in the
comparison cohort, respectively. Fully adjusted HRs (95% CI) were 3.89 (95% CI:
2.28, 6.65) for MI and 1.76 (95% CI: 0.91, 3.40) for stroke. The age-, sex- and
entry time-matched HRs for MI and stroke were highest in the first year after PM
diagnosis (6.51, [95% CI: 3.15, 13.47] and 3.48 [95% CI: 1.26, 9.62],
respectively). Similar trends were seen for DM. CONCLUSION: Our study
demonstrates that PM and DM are both associated with an increased risk of MI but
not ischaemic stroke. Our findings support increased vigilance in cardiovascular
prevention, surveillance and risk modification in adults with PM and DM.
PMID- 26424836
TI - Increased risk of papillary thyroid cancer in systemic sclerosis associated with
autoimmune thyroiditis.
AB - OBJECTIVES: Patients with SSc have an increased risk of malignancy compared with
the general population. Before now, no study has evaluated the risk of thyroid
cancer (TC) in SSc patients. The aim of the study was to evaluate the prevalence
of TC in SSc patients. METHODS: We studied the prevalence of TC in 327 unselected
SSc patients in comparison with two population-based, gender- and age-matched
control groups (654 subjects from an iodine-deficient area and 654 subjects from
an iodine-sufficient area). Thyroid status was assessed by measurement of
circulating thyroid hormones and autoantibodies, thyroid ultrasonography and fine
needle aspiration cytology (when necessary). RESULTS: Circulating thyroid
stimulating hormone, anti-thyroglobulin and anti-thyroperoxidase antibody levels,
and the prevalence of hypothyroidism were significantly higher in SSc patients (P
< 0.01, for all). Six patients with papillary TC (PTC) were detected among SSc
patients, whereas only one case was observed in each of controls 1 and 2 (P =
0.007, for both). In SSc all patients with TC had evidence of thyroid
autoimmunity vs 40% of the other SSc patients (P = 0.001). CONCLUSION: These data
suggest a high prevalence of papillary TC in SSc patients, in particular in the
presence of thyroid autoimmunity; careful thyroid monitoring would be opportune
during the follow-up of these patients.
PMID- 26424837
TI - Biologic efficacy optimization--a step towards personalized medicine.
AB - This following is a review of the factors that influence the outcome of biologic
agents in the treatment of adult RA and, when synthesized into the clinical
decision-making process, enhance optimization. Adiposity can exacerbate
inflammatory diseases; patients with high BMI have worse outcomes from RA,
including TNF inhibitors (TNFis), whereas the efficacy of abatacept and
tocilizumab is unaffected. Smoking adversely affects TNFi outcomes but has less
or no effect on the efficacy of rituximab and tocilizumab, and the effect on
abatacept is unknown. Patients who are positive for ACPA and RF have better
efficacy with rituximab and abatacept than those who are seronegative, whereas
the influence of serotype is less significant for tocilizumab and more complex
for TNFis. All biologics seem to do better when co-prescribed with MTX, whereas
in monotherapy, tocilizumab is superior to adalimumab and prescription of a non
MTX DMARD has advantages over no DMARD for rituximab and adalimumab. Monitoring
of TNFi drug levels is an exciting new field, correlating closely with efficacy
in RA and PsA, and is influenced by BMI, adherence, co-prescribed DMARDs and anti
drug antibodies. The measurement of trough levels provides a potential tool for
patients who are not doing well to determine early whether to switch within the
TNFi class (if levels are low) or to a biologic with an alternative mode of
action (if levels are normal or high). Conversely, the finding of
supratherapeutic levels has the potential to enable individual patient selection
for dose reduction without the risk of flare.
PMID- 26424838
TI - Use of biologics in SLE: a review of the evidence from a clinical perspective.
AB - With the explosion in biologics use in rheumatology, newer and smarter ways of
using these drugs in different diseases have been advocated. SLE has to date been
at the back of the biologics algorithms. Recently, the US Food and Drug
Administration and European Medicines Evaluation Agency licensed belimumab for
use in SLE, the first drug in >30 years. A clinical review of the evidence that
underlies the use of belimumab and other biologics in SLE reveals possible
reasons why the results are not as spectacular as they are in other diseases.
PMID- 26424839
TI - Selective oestrogen receptor modulators lasofoxifene and bazedoxifene inhibit
joint inflammation and osteoporosis in ovariectomised mice with collagen-induced
arthritis.
AB - OBJECTIVE: RA predominantly affects post-menopausal women and is strongly
associated with development of generalised osteoporosis. To find treatments that
target both joint manifestations and osteoporosis in RA is desirable. The third
generation of selective oestrogen receptor modulators (SERMs) [lasofoxifene (LAS)
and bazedoxifene (BZA)] are new treatment options for post-menopausal
osteoporosis. The aim of this study was to investigate the effects of LAS and BZA
on arthritic disease and inflammation-associated bone loss using CIA in mice.
METHODS: Female DBA/1 mice were ovariectomised and subjected to CIA as a model of
post-menopausal RA. Mice received treatment with LAS, BZA, 17beta-estradiol (E2)
as reference or vehicle. Arthritis development was assessed and BMD was
determined by peripheral quantitative CT of the femurs. Serologic markers of
inflammation and cartilage destruction were analysed. Immune cells in lymph nodes
were studied by flow cytometry. RESULTS: LAS and BZA reduced the clinical
severity of arthritis as well as the grade of histologic synovitis and erosions
on cartilage and bone. Moreover, SERMs protected against generalised bone loss in
CIA by increasing trabecular BMD. Both SERMs decreased serum marker of cartilage
destruction and LAS reduced serum IL-6 levels. SERMs did not alter Th17 cells in
lymph nodes as E2 did. CONCLUSION: The anti-osteoporotic drugs LAS and BZA were
found to be potent inhibitors of joint inflammation and bone destruction in
experimental arthritis. This study provides new important knowledge regarding the
treatment regimen of post-menopausal women with RA who suffer from increased risk
for osteoporosis.
PMID- 26424840
TI - Evaluation of the Rapidec Carba NP Test for Detection of Carbapenemases in
Enterobacteriaceae.
AB - This study evaluated the performance of the Rapidec Carba NP test, which was
introduced recently into the market for the detection of carbapenemase production
in a broad spectrum of beta-lactamase-producing Enterobacteriaceae clinical
isolates. In total, 252 clinical Enterobacteriaceae isolates that had been
genetically characterized with respect to carbapenemase, extended-spectrum beta
lactamase (ESBL), and AmpC genes were analyzed; 51/252 isolates (20.2%) were
genetically confirmed to be carbapenemase producers, whereas 201/252 isolates
(79.8%) were genetically negative for the presence of carbapenemase genes. The
Rapidec Carba NP test was applied according to the manufacturer's instructions,
and results were read after 30 and 120 min of incubation. The overall
sensitivity, specificity, positive predictive value (PPV), and negative
predictive value (NPV) of the Rapidec Carba NP test were 90.2%, 100%, 100%, and
97.6%, respectively, when the manufacturer's instructions were followed. Four of
5 false-negative results occurred with OXA-48-like enzymes. After an incubation
time of 30 min, the sensitivity was 49%. The sensitivity increased to 100% when
the recommended bacterial inoculum was doubled and the test was read strictly
after 120 min of incubation. The Rapidec Carba NP test is a useful tool for the
reliable confirmation of carbapenemase-producing Enterobacteriaceae isolates. The
test should be read strictly after 120 min of incubation and the inoculum should
be larger than recommended by the manufacturer.
PMID- 26424841
TI - Simplified Protocol for Carba NP Test for Enhanced Detection of Carbapenemase
Producers Directly from Bacterial Cultures.
AB - We compared carbapenemase detection among 266 Gram-negative bacilli (161
carbapenemase producers) using the Carba NP tests issued by the CLSI (CNPt-CLSI)
and a novel protocol (CNPt-direct) designed for carbapenemase detection direct
from bacterial cultures (instead of bacterial extracts required by the CLSI
tests). The specificities were comparable (100%), but the CNPt-direct was more
sensitive (98% versus 84%). The CNPt-direct was easier to perform due to the
direct use of colonies and offered a more robust detection of carbapenemase
producers.
PMID- 26424842
TI - Comparative Evaluation of Three Nucleic Acid-Based Assays for BK Virus
Quantification.
AB - With the growing importance of BK virus (BKV), effective and efficient screening
for BKV replication in plasma and urine samples is very important for monitoring
renal transplant and hematopoietic stem cell transplant recipients, who are at
increased risk of BKV-associated diseases. However, recent assays proposed by
many manufacturers have not been tested, and the available tests have not been
standardized. The aim of the present study was to evaluate and compare the
performances of three commercially available kits, R-gene, GeneProof, and
RealStar, on plasma and urine specimens from patients infected with various
genotypes and to determine the correlations with the results from a reference
laboratory. A qualitatively excellent global agreement (96.8%) was obtained.
RealStar PCR tended to give a higher sensitivity, especially for subtype Ib1
samples. Comparison of 30 plasma samples and 53 urine samples showed a good
agreement between the three assays, with Spearman's Rho correlation coefficient
values falling between 0.92 and 0.98 (P < 0.001). Moreover, a perfect correlation
was obtained for comparison of the assay performances with the AcroMetrix BKV
panel (P < 0.001 for all comparisons). According to Bland-Altman analysis, more
than 95% (240/249 comparisons) of sample comparisons were situated in the range
of the mean +/- 2 standard deviations (SD). The greatest variability between
assays was observed for 10.2% of subtype Ib2 samples, with differences of >1
log10 copies/ml. In conclusion, this study demonstrated the reliable and
comparable performances of the R-gene, GeneProof, and RealStar real-time PCR
systems for quantification of BKV in urine and plasma samples. All three real
time PCR assays are appropriate for screening of BKV replication in patients.
PMID- 26424844
TI - Characterization of Five Zoonotic Streptococcus suis Strains from Germany,
Including One Isolate from a Recent Fatal Case of Streptococcal Toxic Shock-Like
Syndrome in a Hunter.
AB - A Streptococcus suis isolate from a German hunter with streptococcal toxic shock
like syndrome (STSLS) and four additional zoonotic isolates were genotyped as
mrp(+) epf* (variant 1890) sly(+) cps2(+). All five zoonotic German strains were
characterized by high multiplication in human blood samples ex vivo, but
induction of only low levels of proinflammatory cytokines compared to a Chinese
STSLS strain.
PMID- 26424843
TI - Development of a Multiplex PCR Assay for Rapid Molecular Serotyping of
Haemophilus parasuis.
AB - Haemophilus parasuis causes Glasser's disease and pneumonia in pigs. Indirect
hemagglutination (IHA) is typically used to serotype this bacterium,
distinguishing 15 serovars with some nontypeable isolates. The capsule loci of
the 15 reference strains have been annotated, and significant genetic variation
was identified between serovars, with the exception of serovars 5 and 12. A
capsule locus and in silico serovar were identified for all but two nontypeable
isolates in our collection of >200 isolates. Here, we describe the development of
a multiplex PCR, based on variation within the capsule loci of the 15 serovars of
H. parasuis, for rapid molecular serotyping. The multiplex PCR (mPCR)
distinguished between all previously described serovars except 5 and 12, which
were detected by the same pair of primers. The detection limit of the mPCR was
4.29 * 10(5) ng/MUl bacterial genomic DNA, and high specificity was indicated by
the absence of reactivity against closely related commensal Pasteurellaceae and
other bacterial pathogens of pigs. A subset of 150 isolates from a previously
sequenced H. parasuis collection was used to validate the mPCR with 100% accuracy
compared to the in silico results. In addition, the two in silico-nontypeable
isolates were typeable using the mPCR. A further 84 isolates were analyzed by
mPCR and compared to the IHA serotyping results with 90% concordance (excluding
those that were nontypeable by IHA). The mPCR was faster, more sensitive, and
more specific than IHA, enabling the differentiation of 14 of the 15 serovars of
H. parasuis.
PMID- 26424845
TI - Vancomycin-Variable Enterococcal Bacteremia.
AB - Vancomycin-variable enterococcus (VVE) is an emerging pathogen. VVE isolates
initially appear phenotypically susceptible to vancomycin but possesses the vanA
gene and can develop in vitro and in vivo resistance to vancomycin. We report a
case of VVE bacteremia and describe how VVE poses diagnostic and therapeutic
dilemmas.
PMID- 26424846
TI - Social contacts, vaccination decisions and influenza in Japan.
AB - BACKGROUND: Contact patterns and vaccination decisions are fundamental to
transmission dynamics of infectious diseases. We report on age-specific contact
patterns in Japan and their effect on influenza vaccination behaviour. METHODS:
Japanese adults (N=3146) were surveyed in Spring 2011 to assess the number of
their social contacts within a 24 h period, defined as face-to-face conversations
within 2 m, and gain insight into their influenza-related behaviour. We analysed
the duration and location of contacts according to age. Additionally, we analysed
the probability of vaccination and influenza infection in relation to the number
of contacts controlling for individual's characteristics. RESULTS: The mean and
median reported numbers of daily contacts were 15.3 and 12.0, respectively.
School-aged children and young adults reported the greatest number of daily
contacts, and individuals had the most contacts with those in the same age group.
The age-specific contact patterns were different between men and women, and
differed between weekdays and weekends. Children had fewer contacts between the
same age groups during weekends than during weekdays, due to reduced contacts at
school. The probability of vaccination increased with the number of contacts,
controlling for age and household size. Influenza infection among unvaccinated
individuals was higher than for those vaccinated, and increased with the number
of contacts. CONCLUSIONS: Contact patterns in Japan are age and gender specific.
These contact patterns, as well as their interplay with vaccination decisions and
infection risks, can help inform the parameterisation of mathematical models of
disease transmission and the design of public health policies, to control disease
transmission.
PMID- 26424847
TI - The rise of neoliberalism: how bad economics imperils health and what to do about
it.
AB - The 2008 global financial crisis, precipitated by high-risk, under-regulated
financial practices, is often seen as a singular event. The crisis, its
recessionary consequences, bank bailouts and the adoption of 'austerity' measures
can be seen as a continuation of a 40-year uncontrolled experiment in neoliberal
economics. Although public spending and recapitalisation of failing banks helped
prevent a 1930s-style Great Depression, the deep austerity measures that followed
have stifled a meaningful recovery for the majority of populations. In the short
term, these austerity measures, especially cuts to health and social protection
systems, pose major health risks in those countries under its sway. Meanwhile
structural changes to the global labour market, increasing under-employment in
high-income countries and economic insecurity elsewhere, are likely to widen
health inequities in the longer term. We call for four policy reforms to reverse
rising inequalities and their harms to public health. First is re-regulating
global finance. Second is rejecting austerity as an empirically and ethically
unjustified policy, especially given now clear evidence of its deleterious health
consequences. Third, there is a need to restore progressive taxation at national
and global scales. Fourth is a fundamental shift away from the fossil fuel
economy and policies that promote economic growth in ways that imperil
environmental sustainability. This involves redistributing work and promoting
fairer pay. We do not suggest these reforms will be politically feasible or even
achievable in the short term. They nonetheless constitute an evidence-based
agenda for strong, public health advocacy and practice.
PMID- 26424848
TI - Nucleotide sequence of miRNA precursor contributes to cleavage site selection by
Dicer.
AB - The ribonuclease Dicer excises mature miRNAs from a diverse group of precursors
(pre-miRNAs), most of which contain various secondary structure motifs in their
hairpin stem. In this study, we analyzed Dicer cleavage in hairpin substrates
deprived of such motifs. We searched for the factors other than the secondary
structure, which may influence the length diversity and heterogeneity of miRNAs.
We found that the nucleotide sequence at the Dicer cleavage site influences both
of these miRNA characteristics. With regard to cleavage mechanism, we demonstrate
that the Dicer RNase IIIA domain that cleaves within the 3' arm of the pre-miRNA
is more sensitive to the nucleotide sequence of its substrate than is the RNase
IIIB domain. The RNase IIIA domain avoids releasing miRNAs with G nucleotide and
prefers to generate miRNAs with a U nucleotide at the 5' end. We also propose
that the sequence restrictions at the Dicer cleavage site might be the factor
that contributes to the generation of miRNA duplexes with 3' overhangs of
atypical lengths. This finding implies that the two RNase III domains forming the
single processing center of Dicer may exhibit some degree of flexibility, which
allows for the formation of these non-standard 3' overhangs.
PMID- 26424849
TI - Dynamic modulation of Dnmt2-dependent tRNA methylation by the micronutrient
queuine.
AB - Dnmt2 enzymes are cytosine-5 methyltransferases that methylate C38 of several
tRNAs. We report here that the activities of two Dnmt2 homologs, Pmt1 from
Schizosaccharomyces pombe and DnmA from Dictyostelium discoideum, are strongly
stimulated by prior queuosine (Q) modification of the substrate tRNA. In vivo
tRNA methylation levels were stimulated by growth of cells in queuine-containing
medium; in vitro Pmt1 activity was enhanced on Q-containing RNA; and queuine
stimulated in vivo methylation was abrogated by the absence of the enzyme that
inserts queuine into tRNA, eukaryotic tRNA-guanine transglycosylase. Global
analysis of tRNA methylation in S. pombe showed a striking selectivity of Pmt1
for tRNA(Asp) methylation, which distinguishes Pmt1 from other Dnmt2 homologs.
The present analysis also revealed a novel Pmt1- and Q-independent tRNA
methylation site in S. pombe, C34 of tRNA(Pro). Notably, queuine is a
micronutrient that is scavenged by higher eukaryotes from the diet and gut
microflora. This work therefore reveals an unanticipated route by which the
environment can modulate tRNA modification in an organism.
PMID- 26424850
TI - Femtosecond near-infrared laser microirradiation reveals a crucial role for PARP
signaling on factor assemblies at DNA damage sites.
AB - Laser microirradiation is a powerful tool for real-time single-cell analysis of
the DNA damage response (DDR). It is often found, however, that factor
recruitment or modification profiles vary depending on the laser system employed.
This is likely due to an incomplete understanding of how laser conditions/dosages
affect the amounts and types of damage and the DDR. We compared different
irradiation conditions using a femtosecond near-infrared laser and found distinct
damage site recruitment thresholds for 53BP1 and TRF2 correlating with the dose
dependent increase of strand breaks and damage complexity. Low input-power
microirradiation that induces relatively simple strand breaks led to robust
recruitment of 53BP1 but not TRF2. In contrast, increased strand breaks with
complex damage including crosslinking and base damage generated by high input
power microirradiation resulted in TRF2 recruitment to damage sites with no 53BP1
clustering. We found that poly(ADP-ribose) polymerase (PARP) activation
distinguishes between the two damage states and that PARP activation is essential
for rapid TRF2 recruitment while suppressing 53BP1 accumulation at damage sites.
Thus, our results reveal that careful titration of laser irradiation conditions
allows induction of varying amounts and complexities of DNA damage that are
gauged by differential PARP activation regulating protein assembly at the damage
site.
PMID- 26424851
TI - KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat
viral DNA.
AB - Latency-associated nuclear antigen (LANA) is central to episomal tethering,
replication and transcriptional regulation of gamma2-herpesviruses. LANA binds
cooperatively to the terminal repeat (TR) region of the viral episome via
adjacent LANA binding sites (LBS), but the molecular mechanism by which LANA
assembles on the TR remains elusive. We show that KSHV LANA and MHV-68 LANA
proteins bind LBS DNA using strikingly different modes. Solution structure of
LANA complexes revealed that while kLANA tetramer is intrinsically bent both in
the free and bound state to LBS1-2 DNA, mLANA oligomers instead adopt a rigid
linear conformation. In addition, we report a novel non-ring kLANA structure that
displays more flexibility at its assembly interface than previously demonstrated.
We identified a hydrophobic pivot point located at the dimer-dimer assembly
interface, which gives rotational freedom for kLANA to adopt variable
conformations to accommodate both LBS1-2 and LBS2-1-3 DNA. Alterations in the
arrangement of LBS within TR or at the tetramer assembly interface have a drastic
effect on the ability of kLANA binding. We also show kLANA and mLANA DNA binding
functions can be reciprocated. Although KSHV and MHV-68 are closely related, the
findings provide new insights into how the structure, oligomerization, and DNA
binding of LANA have evolved differently to assemble on the TR DNA.
PMID- 26424852
TI - BacDive--The Bacterial Diversity Metadatabase in 2016.
AB - BacDive-the Bacterial Diversity Metadatabase (http://bacdive.dsmz.de) provides
strain-linked information about bacterial and archaeal biodiversity. The range of
data encompasses taxonomy, morphology, physiology, sampling and concomitant
environmental conditions as well as molecular biology. The majority of data is
manually annotated and curated. Currently (with release 9/2015), BacDive covers
53 978 strains. Newly implemented RESTful web services provide instant access to
the content in machine-readable XML and JSON format. Besides an overall increase
of data content, BacDive offers new data fields and features, e.g. the search for
gene names, plasmids or 16S rRNA in the advanced search, as well as improved
linkage of entries to external life science web resources.
PMID- 26424853
TI - RNA binding to APOBEC3G induces the disassembly of functional deaminase complexes
by displacing single-stranded DNA substrates.
AB - APOBEC3G (A3G) DNA deaminase activity requires a holoenzyme complex whose
assembly on nascent viral reverse transcripts initiates with A3G dimers binding
to ssDNA followed by formation of higher-order A3G homo oligomers. Catalytic
activity is inhibited when A3G binds to RNA. Our prior studies suggested that RNA
inhibited A3G binding to ssDNA. In this report, near equilibrium binding and gel
shift analyses showed that A3G assembly and disassembly on ssDNA was an ordered
process involving A3G dimers and multimers thereof. Although, fluorescence
anisotropy showed that A3G had similar nanomolar affinity for RNA and ssDNA, RNA
stochastically dissociated A3G dimers and higher-order oligomers from ssDNA,
suggesting a different modality for RNA binding. Mass spectrometry mapping of A3G
peptides cross-linked to nucleic acid suggested ssDNA only bound to three
peptides, amino acids (aa) 181-194 in the N-terminus and aa 314-320 and 345-374
in the C-terminus that were part of a continuous exposed surface. RNA bound to
these peptides and uniquely associated with three additional peptides in the N-
terminus, aa 15-29, 41-52 and 83-99, that formed a continuous surface area
adjacent to the ssDNA binding surface. The data predict a mechanistic model of
RNA inhibition of ssDNA binding to A3G in which competitive and allosteric
interactions determine RNA-bound versus ssDNA-bound conformational states.
PMID- 26424854
TI - Similar clinical results of influenza vaccination in peritoneal dialysis and
haemodialysis patients.
PMID- 26424855
TI - missMethyl: an R package for analyzing data from Illumina's HumanMethylation450
platform.
AB - DNA methylation is one of the most commonly studied epigenetic modifications due
to its role in both disease and development. The Illumina HumanMethylation450
BeadChip is a cost-effective way to profile >450 000 CpGs across the human
genome, making it a popular platform for profiling DNA methylation. Here we
introduce missMethyl, an R package with a suite of tools for performing
normalization, removal of unwanted variation in differential methylation
analysis, differential variability testing and gene set analysis for the 450K
array. AVAILABILITY AND IMPLEMENTATION: missMethyl is an R package available from
the Bioconductor project at www.bioconductor.org. CONTACT:
alicia.oshlack@mcri.edu.au SUPPLEMENTARY INFORMATION: Supplementary data are
available at Bioinformatics online.
PMID- 26424856
TI - smallWig: parallel compression of RNA-seq WIG files.
AB - CONTRIBUTIONS: We developed a new lossless compression method for WIG data, named
smallWig, offering the best known compression rates for RNA-seq data and
featuring random access functionalities that enable visualization, summary
statistics analysis and fast queries from the compressed files. Our approach
results in order of magnitude improvements compared with bigWig and ensures
compression rates only a fraction of those produced by cWig. The key features of
the smallWig algorithm are statistical data analysis and a combination of source
coding methods that ensure high flexibility and make the algorithm suitable for
different applications. Furthermore, for general-purpose file compression, the
compression rate of smallWig approaches the empirical entropy of the tested WIG
data. For compression with random query features, smallWig uses a simple block
based compression scheme that introduces only a minor overhead in the compression
rate. For archival or storage space-sensitive applications, the method relies on
context mixing techniques that lead to further improvements of the compression
rate. Implementations of smallWig can be executed in parallel on different sets
of chromosomes using multiple processors, thereby enabling desirable scaling for
future transcriptome Big Data platforms. MOTIVATION: The development of next
generation sequencing technologies has led to a dramatic decrease in the cost of
DNA/RNA sequencing and expression profiling. RNA-seq has emerged as an important
and inexpensive technology that provides information about whole transcriptomes
of various species and organisms, as well as different organs and cellular
communities. The vast volume of data generated by RNA-seq experiments has
significantly increased data storage costs and communication bandwidth
requirements. Current compression tools for RNA-seq data such as bigWig and cWig
either use general-purpose compressors (gzip) or suboptimal compression schemes
that leave significant room for improvement. To substantiate this claim, we
performed a statistical analysis of expression data in different transform
domains and developed accompanying entropy coding methods that bridge the gap
between theoretical and practical WIG file compression rates. RESULTS: We tested
different variants of the smallWig compression algorithm on a number of integer
and real- (floating point) valued RNA-seq WIG files generated by the ENCODE
project. The results reveal that, on average, smallWig offers 18-fold compression
rate improvements, up to 2.5-fold compression time improvements, and 1.5-fold
decompression time improvements when compared with bigWig. On the tested files,
the memory usage of the algorithm never exceeded 90 KB. When more elaborate
context mixing compressors were used within smallWig, the obtained compression
rates were as much as 23 times better than those of bigWig. For smallWig used in
the random query mode, which also supports retrieval of the summary statistics,
an overhead in the compression rate of roughly 3-17% was introduced depending on
the chosen system parameters. An increase in encoding and decoding time of 30%
and 55% represents an additional performance loss caused by enabling random data
access. We also implemented smallWig using multi-processor programming. This
parallelization feature decreases the encoding delay 2-3.4 times compared with
that of a single-processor implementation, with the number of processors used
ranging from 2 to 8; in the same parameter regime, the decoding delay decreased 2
5.2 times. AVAILABILITY AND IMPLEMENTATION: The smallWig software can be
downloaded from: http://stanford.edu/~zhiyingw/smallWig/smallwig.html,
http://publish.illinois.edu/milenkovic/, http://web.stanford.edu/~tsachy/.
CONTACT: zhiyingw@stanford.edu SUPPLEMENTARY INFORMATION: Supplementary data are
available at Bioinformatics online.
PMID- 26424857
TI - ANARCI: antigen receptor numbering and receptor classification.
AB - MOTIVATION: Antibody amino-acid sequences can be numbered to identify equivalent
positions. Such annotations are valuable for antibody sequence comparison,
protein structure modelling and engineering. Multiple different numbering schemes
exist, they vary in the nomenclature they use to annotate residue positions,
their definitions of position equivalence and their popularity within different
scientific disciplines. However, currently no publicly available software exists
that can apply all the most widely used schemes or for which an executable can be
obtained under an open license. RESULTS: ANARCI is a tool to classify and number
antibody and T-cell receptor amino-acid variable domain sequences. It can
annotate sequences with the five most popular numbering schemes: Kabat, Chothia,
Enhanced Chothia, IMGT and AHo. AVAILABILITY AND IMPLEMENTATION: ANARCI is
available for download under GPLv3 license at opig.stats.ox.ac.uk/webapps/anarci.
A web-interface to the program is available at the same address. CONTACT:
deane@stats.ox.ac.uk.
PMID- 26424858
TI - regioneR: an R/Bioconductor package for the association analysis of genomic
regions based on permutation tests.
AB - MOTIVATION: Statistically assessing the relation between a set of genomic regions
and other genomic features is a common challenging task in genomic and epigenomic
analyses. Randomization based approaches implicitly take into account the
complexity of the genome without the need of assuming an underlying statistical
model. SUMMARY: regioneR is an R package that implements a permutation test
framework specifically designed to work with genomic regions. In addition to the
predefined randomization and evaluation strategies, regioneR is fully
customizable allowing the use of custom strategies to adapt it to specific
questions. Finally, it also implements a novel function to evaluate the local
specificity of the detected association. AVAILABILITY AND IMPLEMENTATION:
regioneR is an R package released under Artistic-2.0 License. The source code and
documents are freely available through Bioconductor
(http://www.bioconductor.org/packages/regioneR). CONTACT:
rmalinverni@carrerasresearch.org.
PMID- 26424859
TI - Warpgroup: increased precision of metabolomic data processing by consensus
integration bound analysis.
AB - MOTIVATION: Current informatic techniques for processing raw chromatography/mass
spectrometry data break down under several common, non-ideal conditions.
Importantly, hydrophilic liquid interaction chromatography (a key separation
technology for metabolomics) produces data which are especially challenging to
process. We identify three critical points of failure in current informatic
workflows: compound specific drift, integration region variance, and naive
missing value imputation. We implement the Warpgroup algorithm to address these
challenges. RESULTS: Warpgroup adds peak subregion detection, consensus
integration bound detection, and intelligent missing value imputation steps to
the conventional informatic workflow. When compared with the conventional
workflow, Warpgroup made major improvements to the processed data. The
coefficient of variation for peaks detected in replicate injections of a complex
Escherichia Coli extract were halved (a reduction of 19%). Integration regions
across samples were much more robust. Additionally, many signals lost by the
conventional workflow were 'rescued' by the Warpgroup refinement, thereby
resulting in greater analyte coverage in the processed data. AVAILABILITY AND: I:
MPLEMENTATION: Warpgroup is an open source R package available on GitHub at
github.com/nathaniel-mahieu/warpgroup. The package includes example data and XCMS
compatibility wrappers for ease of use. SUPPLEMENTARY INFORMATION: Supplementary
data are available at Bioinformatics online. CONTACT: nathaniel.mahieu@wustl.edu
or gjpattij@wustl.edu.
PMID- 26424860
TI - A mandibular advancement device did not affect daytime sleepiness and quality of
life in obstructive sleep apnoea.
PMID- 26424861
TI - Paediatric pain-related conditions impact healthcare expenditures.
PMID- 26424862
TI - Dialectical behaviour therapy with skills training seems to be more effective in
reducing non-suicidal self-injury.
PMID- 26424863
TI - Burden of bullying: enduring effects of early victimisation on depression in
adulthood.
PMID- 26424864
TI - Improving methadone maintenance therapy for prisoner populations.
PMID- 26424867
TI - Erratum.
PMID- 26424865
TI - The ORBIT bleeding score: a simple bedside score to assess bleeding risk in
atrial fibrillation.
AB - BACKGROUND: Therapeutic decisions in atrial fibrillation (AF) are often
influenced by assessment of bleeding risk. However, existing bleeding risk scores
have limitations. OBJECTIVES: We sought to develop and validate a novel bleeding
risk score using routinely available clinical information to predict major
bleeding in a large, community-based AF population. METHODS: We analysed data
from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation
(ORBIT-AF), a prospective registry that enrolled incident and prevalent AF
patients at 176 US sites. Using Cox proportional hazards regression, we
identified factors independently associated with major bleeding among patients
taking oral anticoagulation (OAC) over a median follow-up of 2 years
(interquartile range = 1.6-2.5). We also created a numerical bedside risk score
that included the five most predictive risk factors weighted according to their
strength of association with major bleeding. The predictive performance of the
full model, the simple five-item score, and two existing risk scores
(hypertension, abnormal renal/liver function, stroke, bleeding history or
predisposition, labile INR, elderly, drugs/alcohol concomitantly, HAS-BLED, and
anticoagulation and risk factors in atrial fibrillation, ATRIA) were then
assessed in both the ORBIT-AF cohort and a separate clinical trial population,
Rivaroxaban Once-daily oral direct factor Xa inhibition compared with vitamin K
antagonism for prevention of stroke and embolism trial in atrial fibrillation
(ROCKET-AF). RESULTS: Among 7411 ORBIT-AF patients taking OAC, the rate of major
bleeding was 4.0/100 person-years. The full continuous model (12 variables) and
five-factor ORBIT risk score (older age [75+ years], reduced
haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney
function, and treatment with antiplatelet) both had good ability to identify
those who bled vs. not (C-index 0.69 and 0.67, respectively). These scores both
had similar discrimination, but markedly better calibration when compared with
the HAS-BLED and ATRIA scores in an external validation population from the
ROCKET-AF trial. CONCLUSIONS: The five-element ORBIT bleeding risk score had
better ability to predict major bleeding in AF patients when compared with HAS
BLED and ATRIA risk scores. The ORBIT risk score can provide a simple, easily
remembered tool to support clinical decision making.
PMID- 26424868
TI - Erratum.
PMID- 26424866
TI - Imaging of congenital heart disease in adults.
AB - Imaging is fundamental to the lifelong care of adult congenital heart disease
(ACHD) patients. Echocardiography remains the first line imaging for inpatient,
outpatient, or perioperative care. Cross-sectional imaging with cardiovascular
magnetic resonance (CMR) or computed tomography (CT) provides complementary and
invaluable information on cardiac and vascular anatomy and other intra-thoracic
structures. Furthermore, CMR provides quantification of cardiac function and
vascular flow. Cardiac catheterization is mostly reserved for assessment of
pulmonary vascular resistance, ventricular end-diastolic pressure, and
percutaneous interventions. There have been further advances in non-invasive
imaging for ACHD including the application of advanced echocardiographic
techniques, faster automated CMR imaging, and radiation dose reduction in CT. As
a result ACHD, a heterogeneous population, benefit from appropriate application
of multiple imaging modalities matched with tertiary ACHD expertise.
PMID- 26424869
TI - Blood transfusion and the benefit/harm inflection point.
PMID- 26424870
TI - Reply to Fisher et al.
PMID- 26424871
TI - Are intraoperative flow measurements sufficient to allay concerns about flow
capacity of skeletonized internal thoracic arteries?
PMID- 26424872
TI - Early dysfunction of a tricuspid valve-in-valve replacement due to papillary
muscle overgrowth.
PMID- 26424873
TI - Intraoperative bleeding control by uniportal video-assisted thoracoscopic
surgery?.
AB - Owing to advances in video-assisted thoracic surgery (VATS), the majority of
pulmonary resections can currently be performed by VATS in a safe manner with a
low level of morbidity and mortality. The majority of the complications that
occur during VATS can be minimized with correct preoperative planning of the case
as well as careful pulmonary dissection. Coordination of the whole surgical team
is essential when confronting an emergency such as major bleeding. This is
particularly important during the VATS learning curve, where the occurrence of
intraoperative complications, particularly significant bleeding, usually ends in
a conversion to open surgery. However, conversion should not be considered as a
failure of the VATS approach, but as a resource to maintain the patient's safety.
The correct assessment of any bleeding is of paramount importance during major
thoracoscopic procedures. Inadequate management of the source of bleeding may
result in major vessel injury and massive bleeding. If bleeding occurs, a sponge
stick should be readily available to apply pressure immediately to control the
haemorrhage. It is always important to remain calm and not to panic. With the
bleeding temporarily controlled, a decision must be made promptly as to whether a
thoracotomy is needed or if the bleeding can be solved through the VATS approach.
This will depend primarily on the surgeon's experience. The operative vision
provided with high-definition cameras, specially designed or adapted instruments
and the new sealants are factors that facilitate the surgeon's control. After
experience has been acquired with conventional or uniportal VATS, the rate of
complications diminishes and the majority of bleeding events are controlled
without the need for conversion to thoracotomy.
PMID- 26424874
TI - Hard and Soft Selection Revisited: How Evolution by Natural Selection Works in
the Real World.
AB - The modern synthesis of evolutionary biology unified Darwin's natural selection
with Mendelian genetics, but at the same time it created the dilemma of genetic
load. Lewontin and Hubby's (1966) and Harris's (1966) characterization of genetic
variation in natural populations increased the apparent burden of this load.
Neutrality or near neutrality of genetic variation was one mechanism proposed for
the revealed excessive genetic variation. Bruce Wallace coined the term "soft
selection" to describe an alternative way for natural selection to operate that
was consistent with observed variation. He envisioned nature as presenting
ecological vacancies that could be filled by diverse genotypes. Survival and
successful reproduction was a combined function of population density, genotype,
and genotype frequencies, rather than a fixed value of the relative fitness of
each genotype. My goal in this review is to explore the importance of soft
selection in the real world. My motive and that of my colleagues as described
here is not to explain what maintains genetic variation in natural populations,
but rather to understand the factors that shape how organisms adapt to natural
environments. We characterize how feedbacks between ecology and evolution shape
both evolution and ecology. These feedbacks are mediated by density- and
frequency-dependent selection, the mechanisms that underlie soft selection. Here,
I report on our progress in characterizing these types of selection with a
combination of a consideration of the published literature and the results from
my collaborators' and my research on natural populations of guppies.
PMID- 26424875
TI - Disrupting the Perception of Effort with Continuous Theta Burst Stimulation.
PMID- 26424876
TI - Opioid Inhibition of Intercalated Input to the Central Amygdala.
PMID- 26424877
TI - Neuronal Store-Operated Calcium Entry and Mushroom Spine Loss in Amyloid
Precursor Protein Knock-In Mouse Model of Alzheimer's Disease.
AB - Alzheimer's disease (AD) is the most common reason for elderly dementia in the
world. We proposed that memory loss in AD is related to destabilization of
mushroom postsynaptic spines involved in long-term memory storage. We
demonstrated previously that stromal interaction molecule 2 (STIM2)-regulated
neuronal store-operated calcium entry (nSOC) in postsynaptic spines play a key
role in stability of mushroom spines by maintaining activity of synaptic
Ca(2+)/calmodulin kinase II (CaMKII). Furthermore, we demonstrated previously
that the STIM2-nSOC-CaMKII pathway is downregulated in presenilin 1 M146V knock
in (PS1-M146V KI) mouse model of AD, leading to loss of hippocampal mushroom
spines in this model. In the present study, we demonstrate that hippocampal
mushroom postsynaptic spines are also lost in amyloid precursor protein knock-in
(APPKI) mouse model of AD. We demonstrated that loss of mushroom spines occurs as
a result of accumulation of extracellular beta-amyloid 42 in APPKI culture media.
Our results indicate that extracellular Abeta42 acts by overactivating mGluR5
receptor in APPKI neurons, leading to elevated Ca(2+) levels in endoplasmic
reticulum, compensatory downregulation of STIM2 expression, impaired synaptic
nSOC, and reduced CaMKII activity. Pharmacological inhibition of mGluR5 or
overexpression of STIM2 rescued synaptic nSOC and prevented mushroom spine loss
in APPKI hippocampal neurons. Our results indicate that downregulation of
synaptic STIM2-nSOC-CaMKII pathway causes loss of mushroom synaptic spines in
both presenilin and APPKI mouse models of AD. We propose that
modulators/activators of this pathway may have a potential therapeutic value for
treatment of memory loss in AD. Significance statement: A direct connection
between amyloid-induced synaptic mushroom spine loss and neuronal store-operated
calcium entry pathway is shown. These results provide strong support for the
calcium hypothesis of neurodegeneration and further validate the synaptic store
operated calcium entry pathway as a potential therapeutic target for Alzheimer's
disease.
PMID- 26424878
TI - Gaze Direction Modulates the Relation between Neural Responses to Faces and
Visual Awareness.
AB - Gaze direction and especially direct gaze is a powerful nonverbal cue that plays
an important role in social interactions. Here we studied the neural mechanisms
underlying the privileged access of direct gaze to visual awareness. We performed
functional magnetic resonance imaging in healthy human volunteers who were
exposed to faces with direct or averted gaze under continuous flash suppression,
thereby manipulating their awareness of the faces. A gaze processing network
comprising fusiform face area (FFA), superior temporal sulcus, amygdala, and
intraparietal sulcus showed overall reduced neural responses when participants
reported to be unaware of the faces. Interestingly, direct gaze elicited greater
responses than averted gaze when participants were aware of the faces, but
smaller responses when they were unaware. Additional between-subject correlation
and single-trial analyses indicated that this pattern of results was due to a
modulation of the relationship between neural responses and awareness by gaze
direction: with increasing neural activation in the FFA, direct-gaze faces
entered awareness more readily than averted-gaze faces. These findings suggest
that for direct gaze, lower levels of neural activity are sufficient to give rise
to awareness than for averted gaze, thus providing a neural basis for privileged
access of direct gaze to awareness. Significance statement: Another person's eye
gaze directed at oneself is a powerful social signal acting as a catalyst for
further communication. Here, we studied the neural mechanisms underlying the
prioritized access of direct gaze to visual awareness in healthy human volunteers
and show that with increasing neural activation, direct-gaze faces enter
awareness more readily than averted-gaze faces. This suggests that for a socially
highly relevant cue like direct gaze, lower levels of neural activity are
sufficient to give rise to awareness compared with averted gaze, possibly because
the human brain is attuned to the efficient neural processing of direct gaze due
to the biological importance of eye contact for social interactions.
PMID- 26424879
TI - Sleep Regulates Incubation of Cocaine Craving.
AB - After withdrawal from cocaine, chronic cocaine users often experience persistent
reduction in total sleep time, which is accompanied by increased sleep
fragmentation resembling chronic insomnia. This and other sleep abnormalities
have long been speculated to foster relapse and further drug addiction, but
direct evidence is lacking. Here, we report that after prolonged withdrawal from
cocaine self-administration, rats exhibited persistent reduction in nonrapid-eye
movement (NREM) and rapid-eye-movement (REM) sleep, as well as increased sleep
fragmentation. In an attempt to improve sleep after cocaine withdrawal, we
applied chronic sleep restriction to the rats during their active (dark) phase of
the day, which selectively decreased the fragmentation of REM sleep during their
inactive (light) phase without changing NREM or the total amount of daily sleep.
Animals with improved REM sleep exhibited decreased incubation of cocaine
craving, a phenomenon depicting the progressive intensification of cocaine
seeking after withdrawal. In contrast, experimentally increasing sleep
fragmentation after cocaine self-administration expedited the development of
incubation of cocaine craving. Incubation of cocaine craving is partially
mediated by progressive accumulation of calcium-permeable AMPA receptors (CP
AMPARs) in the nucleus accumbens (NAc). After withdrawal from cocaine, animals
with improved REM sleep exhibited reduced accumulation of CP-AMPARs in the NAc,
whereas increasing sleep fragmentation accelerated NAc CP-AMPAR accumulation.
These results reveal a potential molecular substrate that can be engaged by sleep
to regulate cocaine craving and relapse, and demonstrate sleep-based therapeutic
opportunities for cocaine addiction. Significance statement: Sleep abnormalities
are common symptoms in chronic drug users long after drug withdrawal. These
withdrawal-associated sleep symptoms, particularly reduction in total sleep time
and deteriorating sleep quality, have been speculated to foster relapse and
further drug addiction, but direct evidence is lacking. Here we show in rats that
the sleep pattern was persistently changed long after withdrawal from cocaine
self-administration, and demonstrate that sleep interventions can bidirectionally
regulate cocaine craving and seeking after withdrawal. We further demonstrate
that glutamatergic synapses in the nucleus accumbens are potential neuronal
targets for sleep intervention to influence cocaine craving after withdrawal.
These results provide a strong rationale supporting sleep-based therapies for
cocaine addiction.
PMID- 26424880
TI - Distinct Functional Modules for Discrete and Rhythmic Forelimb Movements in the
Mouse Motor Cortex.
AB - Movements of animals are composed of two fundamental dynamics: discrete and
rhythmic movements. Although the movements with distinct dynamics are thought to
be differently processed in the CNS, it is unclear how they are represented in
the cerebral cortex. Here, we investigated the cortical representation of
movement dynamics by developing prolonged transcranial optogenetic stimulation
(pTOS) using awake, channelrhodopsin-2 transgenic mice. We found two domains that
induced discrete forelimb movements in the forward and backward directions, and
these sandwiched a domain that generated rhythmic forelimb movements. The forward
discrete movement had an intrinsic velocity profile and the rhythmic movement had
an intrinsic oscillation frequency. Each of the forward discrete and rhythmic
domains possessed intracortical synaptic connections within its own domain,
independently projected to the spinal cord, and weakened the neuronal activity
and movement induction of the other domain. pTOS-induced movements were also
classified as ethologically relevant movements. Forepaw-to-mouth movement was
mapped in a part of the forward discrete domain, while locomotion-like movement
was in a part of the rhythmic domain. Interestingly, photostimulation of the
rhythmic domain resulted in a nonrhythmic, continuous lever-pull movement when a
lever was present. The motor cortex possesses functional modules for distinct
movement dynamics, and these can adapt to environmental constraints for
purposeful movements. Significance statement: Animal behavior has discrete and
rhythmic components, such as reaching and locomotion. It is unclear how these
movements with distinct dynamics are represented in the cerebral cortex. We
investigated the dynamics of movements induced by long-duration transcranial
photostimulation on the dorsal cortex of awake channelrhodopsin-2 transgenic
mice. We found two domains causing forward and backward discrete forelimb
movements and a domain for rhythmic forelimb movements. A domain for forward
discrete movement and a domain for rhythmic movement mutually weakened neuronal
activity and movement size. The photostimulation of the rhythmic domain also
induced nonrhythmic, lever-pull movement, when the lever was present. Thus, the
motor cortex has functional modules with distinct dynamics, and each module
retains flexibility for adaptation to different environments.
PMID- 26424881
TI - Bidirectional Modulation of Recognition Memory.
AB - Perirhinal cortex (PER) has a well established role in the familiarity-based
recognition of individual items and objects. For example, animals and humans with
perirhinal damage are unable to distinguish familiar from novel objects in
recognition memory tasks. In the normal brain, perirhinal neurons respond to
novelty and familiarity by increasing or decreasing firing rates. Recent work
also implicates oscillatory activity in the low-beta and low-gamma frequency
bands in sensory detection, perception, and recognition. Using optogenetic
methods in a spontaneous object exploration (SOR) task, we altered recognition
memory performance in rats. In the SOR task, normal rats preferentially explore
novel images over familiar ones. We modulated exploratory behavior in this task
by optically stimulating channelrhodopsin-expressing perirhinal neurons at
various frequencies while rats looked at novel or familiar 2D images. Stimulation
at 30-40 Hz during looking caused rats to treat a familiar image as if it were
novel by increasing time looking at the image. Stimulation at 30-40 Hz was not
effective in increasing exploration of novel images. Stimulation at 10-15 Hz
caused animals to treat a novel image as familiar by decreasing time looking at
the image, but did not affect looking times for images that were already
familiar. We conclude that optical stimulation of PER at different frequencies
can alter visual recognition memory bidirectionally. Significance statement:
Recognition of novelty and familiarity are important for learning, memory, and
decision making. Perirhinal cortex (PER) has a well established role in the
familiarity-based recognition of individual items and objects, but how novelty
and familiarity are encoded and transmitted in the brain is not known. Perirhinal
neurons respond to novelty and familiarity by changing firing rates, but recent
work suggests that brain oscillations may also be important for recognition. In
this study, we showed that stimulation of the PER could increase or decrease
exploration of novel and familiar images depending on the frequency of
stimulation. Our findings suggest that optical stimulation of PER at specific
frequencies can predictably alter recognition memory.
PMID- 26424883
TI - Fast Learning with Weak Synaptic Plasticity.
AB - New sensory stimuli can be learned with a single or a few presentations.
Similarly, the responses of cortical neurons to a stimulus have been shown to
increase reliably after just a few repetitions. Long-term memory is thought to be
mediated by synaptic plasticity, but in vitro experiments in cortical cells
typically show very small changes in synaptic strength after a pair of
presynaptic and postsynaptic spikes. Thus, it is traditionally thought that fast
learning requires stronger synaptic changes, possibly because of neuromodulation.
Here we show theoretically that weak synaptic plasticity can, in fact, support
fast learning, because of the large number of synapses N onto a cortical neuron.
In the fluctuation-driven regime characteristic of cortical neurons in vivo, the
size of membrane potential fluctuations grows only as ?N, whereas a single output
spike leads to potentiation of a number of synapses proportional to N. Therefore,
the relative effect of a single spike on synaptic potentiation grows as ?N. This
leverage effect requires precise spike timing. Thus, the large number of synapses
onto cortical neurons allows fast learning with very small synaptic changes.
Significance statement: Long-term memory is thought to rely on the strengthening
of coactive synapses. This physiological mechanism is generally considered to be
very gradual, and yet new sensory stimuli can be learned with just a few
presentations. Here we show theoretically that this apparent paradox can be
solved when there is a tight balance between excitatory and inhibitory input. In
this case, small synaptic modifications applied to the many synapses onto a given
neuron disrupt that balance and produce a large effect even for modifications
induced by a single stimulus. This effect makes fast learning possible with small
synaptic changes and reconciles physiological and behavioral observations.
PMID- 26424882
TI - The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal
Amacrine Cell of the Rabbit Retina.
AB - Much of the computational power of the retina derives from the activity of
amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory
interneurons. Here, we identify an ON-type orientation-selective, wide-field,
polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its
orientation selectivity arises from the structure of the dendritic arbor and the
pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and
inhibition arising from the OFF pathway converge to generate a quasi-linear
integration of visual signals in the receptive field center. This serves to
suppress responses to high spatial frequencies, thereby improving sensitivity to
larger objects and enhancing orientation selectivity. Inhibition also regulates
the magnitude and time course of excitatory inputs to this PAC through serial
inhibitory connections onto the presynaptic terminals of ON bipolar cells. This
presynaptic inhibition is driven by graded potentials within local microcircuits,
similar in extent to the size of single bipolar cell receptive fields. Additional
presynaptic inhibition is generated by spiking amacrine cells on a larger spatial
scale covering several hundred microns. The orientation selectivity of this PAC
may be a substrate for the inhibition that mediates orientation selectivity in
some types of ganglion cells. Significance statement: The retina comprises
numerous excitatory and inhibitory circuits that encode specific features in the
visual scene, such as orientation, contrast, or motion. Here, we identify a wide
field inhibitory neuron that responds to visual stimuli of a particular
orientation, a feature selectivity that is primarily due to the elongated shape
of the dendritic arbor. Integration of convergent excitatory and inhibitory
inputs from the ON and OFF visual pathways suppress responses to small objects
and fine textures, thus enhancing selectivity for larger objects. Feedback
inhibition regulates the strength and speed of excitation on both local and wide
field spatial scales. This study demonstrates how different synaptic inputs are
regulated to tune a neuron to respond to specific features in the visual scene.
PMID- 26424884
TI - Motor Cortex Activity Organizes the Developing Rubrospinal System.
AB - The corticospinal and rubrospinal systems function in skilled movement control. A
key question is how do these systems develop the capacity to coordinate their
motor functions and, in turn, if the red nucleus/rubrospinal tract (RN/RST)
compensates for developmental corticospinal injury? We used the cat to
investigate whether the developing rubrospinal system is shaped by activity
dependent interactions with the developing corticospinal system. We unilaterally
inactivated M1 by muscimol microinfusion between postnatal weeks 5 and 7 to
examine activity-dependent interactions and whether the RN/RST compensates for
corticospinal tract (CST) developmental motor impairments and CST misprojections
after M1 inactivation. We examined the RN motor map and RST cervical projections
at 7 weeks of age, while the corticospinal system was inactivated, and at 14
weeks, after activity returned. During M1 inactivation, the RN on the same side
showed normal RST projections and reduced motor thresholds, suggestive of
precocious development. By contrast, the RN on the untreated/active M1 side
showed sparse RST projections and an immature motor map. After M1 activity
returned later in adolescent cat development, RN on the active M1/CST side
continued to show a substantial loss of spinal terminations and an impaired motor
map. RN/RST on the inactivated side regressed to a smaller map and fewer axons.
Our findings suggest that the developing rubrospinal system is under activity
dependent regulation by the corticospinal system for establishing mature RST
connections and RN motor map. The lack of RS compensation on the non-inactivated
side can be explained by development of ipsilateral misprojections from the
active M1 that outcompete the RST. Significance statement: Skilled movements
reflect the activity of multiple descending motor systems and their interactions
with spinal motor circuits. Currently, there is little insight into whether motor
systems interact during development to coordinate their emerging functions and,
if so, the mechanisms underlying this process. This study examined activity
dependent interactions between the developing corticospinal and rubrospinal
systems, two key systems for skilled limb movements. We show that the developing
rubrospinal system competes with the corticospinal system in establishing the red
nucleus motor map and rubrospinal tract connections. This is the first
demonstration of one motor system steering development, and ultimately function,
of another. Knowledge of activity-dependent competition between these two systems
helps predict the response of the rubrospinal system following corticospinal
system developmental injury.
PMID- 26424885
TI - Astrocyte Ca2+ Signaling Drives Inversion of Neurovascular Coupling after
Subarachnoid Hemorrhage.
AB - Physiologically, neurovascular coupling (NVC) matches focal increases in neuronal
activity with local arteriolar dilation. Astrocytes participate in NVC by sensing
increased neurotransmission and releasing vasoactive agents (e.g., K(+)) from
perivascular endfeet surrounding parenchymal arterioles. Previously, we
demonstrated an increase in the amplitude of spontaneous Ca(2+) events in
astrocyte endfeet and inversion of NVC from vasodilation to vasoconstriction in
brain slices obtained from subarachnoid hemorrhage (SAH) model rats. However, the
role of spontaneous astrocyte Ca(2+) signaling in determining the polarity of the
NVC response remains unclear. Here, we used two-photon imaging of Fluo-4-loaded
rat brain slices to determine whether altered endfoot Ca(2+) signaling underlies
SAH-induced inversion of NVC. We report a time-dependent emergence of endfoot
high-amplitude Ca(2+) signals (eHACSs) after SAH that were not observed in
endfeet from unoperated animals. Furthermore, the percentage of endfeet with
eHACSs varied with time and paralleled the development of inversion of NVC.
Endfeet with eHACSs were present only around arterioles exhibiting inversion of
NVC. Importantly, depletion of intracellular Ca(2+) stores using cyclopiazonic
acid abolished SAH-induced eHACSs and restored arteriolar dilation in SAH brain
slices to two mediators of NVC (a rise in endfoot Ca(2+) and elevation of
extracellular K(+)). These data indicate a causal link between SAH-induced eHACSs
and inversion of NVC. Ultrastructural examination using transmission electron
microscopy indicated that a similar proportion of endfeet exhibiting eHACSs also
exhibited asymmetrical enlargement. Our results demonstrate that subarachnoid
blood causes a delayed increase in the amplitude of spontaneous intracellular
Ca(2+) release events leading to inversion of NVC. Significance statement:
Aneurysmal subarachnoid hemorrhage (SAH)--strokes involving cerebral aneurysm
rupture and release of blood onto the brain surface--are associated with high
rates of morbidity and mortality. A common complication observed after SAH is the
development of delayed cerebral ischemia at sites often remote from the site of
rupture. Here, we provide evidence that SAH-induced changes in astrocyte Ca(2+)
signaling lead to a switch in the polarity of the neurovascular coupling response
from vasodilation to vasoconstriction. Thus, after SAH, signaling events that
normally lead to vasodilation and enhanced delivery of blood to active brain
regions cause vasoconstriction that would limit cerebral blood flow. These
findings identify astrocytes as a key player in SAH-induced decreased cortical
blood flow.
PMID- 26424886
TI - Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic
Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse.
AB - Wingless-related MMTV integration site 1 (WNT1)/beta-catenin signaling plays a
crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons,
including the substantia nigra pars compacta (SNc) subpopulation that
preferentially degenerates in Parkinson's disease (PD). However, the precise
functions of WNT1/beta-catenin signaling in this context remain unknown. Stem
cell-based regenerative (transplantation) therapies for PD have not been
implemented widely in the clinical context, among other reasons because of the
heterogeneity and incomplete differentiation of the transplanted cells. This
might result in tumor formation and poor integration of the transplanted cells
into the dopaminergic circuitry of the brain. Dickkopf 3 (DKK3) is a secreted
glycoprotein implicated in the modulation of WNT/beta-catenin signaling. Using
mutant mice, primary ventral midbrain cells, and pluripotent stem cells, we show
that DKK3 is necessary and sufficient for the correct differentiation of a
rostrolateral mdDA neuron subset. Dkk3 transcription in the murine ventral
midbrain coincides with the onset of mdDA neurogenesis and is required for the
activation and/or maintenance of LMX1A (LIM homeobox transcription factor 1alpha)
and PITX3 (paired-like homeodomain transcription factor 3) expression in the
corresponding mdDA precursor subset, without affecting the proliferation or
specification of their progenitors. Notably, the treatment of differentiating
pluripotent stem cells with recombinant DKK3 and WNT1 proteins also increases the
proportion of mdDA neurons with molecular SNc DA cell characteristics in these
cultures. The specific effects of DKK3 on the differentiation of rostrolateral
mdDA neurons in the murine ventral midbrain, together with its known prosurvival
and anti-tumorigenic properties, make it a good candidate for the improvement of
regenerative and neuroprotective strategies in the treatment of PD. Significance
statement: We show here that Dickkopf 3 (DKK3), a secreted modulator of WNT
(Wingless-related MMTV integration site)/beta-catenin signaling, is both
necessary and sufficient for the proper differentiation and survival of a
rostrolateral (parabrachial pigmented nucleus and dorsomedial substantia nigra
pars compacta) mesodiencephalic dopaminergic neuron subset, using Dkk3 mutant
mice and murine primary ventral midbrain and pluripotent stem cells. The
progressive loss of these dopamine-producing mesodiencephalic neurons is a
hallmark of human Parkinson's disease, which can up to now not be halted by
clinical treatments of this disease. Thus, the soluble DKK3 protein might be a
promising new agent for the improvement of current protocols for the directed
differentiation of pluripotent and multipotent stem cells into mesodiencephalic
dopaminergic neurons and for the promotion of their survival in situ.
PMID- 26424888
TI - Modulation of Neuronal Responses by Exogenous Attention in Macaque Primary Visual
Cortex.
AB - Visual perception is influenced by attention deployed voluntarily or triggered
involuntarily by salient stimuli. Modulation of visual cortical processing by
voluntary or endogenous attention has been extensively studied, but much less is
known about how involuntary or exogenous attention affects responses of visual
cortical neurons. Using implanted microelectrode arrays, we examined the effects
of exogenous attention on neuronal responses in the primary visual cortex (V1) of
awake monkeys. A bright annular cue was flashed either around the receptive
fields of recorded neurons or in the opposite visual field to capture attention.
A subsequent grating stimulus probed the cue-induced effects. In a fixation task,
when the cue-to-probe stimulus onset asynchrony (SOA) was <240 ms, the cue
induced a transient increase of neuronal responses to the probe at the cued
location during 40-100 ms after the onset of neuronal responses to the probe.
This facilitation diminished and disappeared after repeated presentations of the
same cue but recurred for a new cue of a different color. In another task to
detect the probe, relative shortening of monkey's reaction times for the validly
cued probe depended on the SOA in a way similar to the cue-induced V1
facilitation, and the behavioral and physiological cueing effects remained after
repeated practice. Flashing two cues simultaneously in the two opposite visual
fields weakened or diminished both the physiological and behavioral cueing
effects. Our findings indicate that exogenous attention significantly modulates
V1 responses and that the modulation strength depends on both novelty and task
relevance of the stimulus. Significance statement: Visual attention can be
involuntarily captured by a sudden appearance of a conspicuous object, allowing
rapid reactions to unexpected events of significance. The current study
discovered a correlate of this effect in monkey primary visual cortex. An abrupt,
salient, flash enhanced neuronal responses, and shortened the animal's reaction
time, to a subsequent visual probe stimulus at the same location. However, the
enhancement of the neural responses diminished after repeated exposures to this
flash if the animal was not required to react to the probe. Moreover, a second,
simultaneous, flash at another location weakened the neuronal and behavioral
effects of the first one. These findings revealed, beyond the observations
reported so far, the effects of exogenous attention in the brain.
PMID- 26424887
TI - Simple Learned Weighted Sums of Inferior Temporal Neuronal Firing Rates
Accurately Predict Human Core Object Recognition Performance.
AB - To go beyond qualitative models of the biological substrate of object
recognition, we ask: can a single ventral stream neuronal linking hypothesis
quantitatively account for core object recognition performance over a broad range
of tasks? We measured human performance in 64 object recognition tests using
thousands of challenging images that explore shape similarity and identity
preserving object variation. We then used multielectrode arrays to measure
neuronal population responses to those same images in visual areas V4 and
inferior temporal (IT) cortex of monkeys and simulated V1 population responses.
We tested leading candidate linking hypotheses and control hypotheses, each
postulating how ventral stream neuronal responses underlie object recognition
behavior. Specifically, for each hypothesis, we computed the predicted
performance on the 64 tests and compared it with the measured pattern of human
performance. All tested hypotheses based on low- and mid-level visually evoked
activity (pixels, V1, and V4) were very poor predictors of the human behavioral
pattern. However, simple learned weighted sums of distributed average IT firing
rates exactly predicted the behavioral pattern. More elaborate linking hypotheses
relying on IT trial-by-trial correlational structure, finer IT temporal codes, or
ones that strictly respect the known spatial substructures of IT ("face patches")
did not improve predictive power. Although these results do not reject those more
elaborate hypotheses, they suggest a simple, sufficient quantitative model: each
object recognition task is learned from the spatially distributed mean firing
rates (100 ms) of ~60,000 IT neurons and is executed as a simple weighted sum of
those firing rates. Significance statement: We sought to go beyond qualitative
models of visual object recognition and determine whether a single neuronal
linking hypothesis can quantitatively account for core object recognition
behavior. To achieve this, we designed a database of images for evaluating object
recognition performance. We used multielectrode arrays to characterize hundreds
of neurons in the visual ventral stream of nonhuman primates and measured the
object recognition performance of >100 human observers. Remarkably, we found that
simple learned weighted sums of firing rates of neurons in monkey inferior
temporal (IT) cortex accurately predicted human performance. Although previous
work led us to expect that IT would outperform V4, we were surprised by the
quantitative precision with which simple IT-based linking hypotheses accounted
for human behavior.
PMID- 26424889
TI - Zac1 Regulates the Differentiation and Migration of Neocortical Neurons via Pac1.
AB - Imprinted genes are dosage sensitive, and their dysregulated expression is linked
to disorders of growth and proliferation, including fetal and postnatal growth
restriction. Common sequelae of growth disorders include neurodevelopmental
defects, some of which are indirectly related to placental insufficiency.
However, several growth-associated imprinted genes are also expressed in the
embryonic CNS, in which their aberrant expression may more directly affect
neurodevelopment. To test whether growth-associated genes influence neural
lineage progression, we focused on the maternally imprinted gene Zac1. In humans,
either loss or gain of ZAC1 expression is associated with reduced growth rates
and intellectual disability. To test whether increased Zac1 expression directly
perturbs neurodevelopment, we misexpressed Zac1 in murine neocortical
progenitors. The effects were striking: Zac1 delayed the transition of apical
radial glial cells to basal intermediate neuronal progenitors and postponed their
subsequent differentiation into neurons. Zac1 misexpression also blocked neuronal
migration, with Zac1-overexpressing neurons pausing more frequently and forming
fewer neurite branches during the period when locomoting neurons undergo dynamic
morphological transitions. Similar, albeit less striking, neuronal migration and
morphological defects were observed on Zac1 knockdown, indicating that Zac1
levels must be regulated precisely. Finally, Zac1 controlled neuronal migration
by regulating Pac1 transcription, a receptor for the neuropeptide pituitary
adenylate cyclase-activating polypeptide (PACAP). Pac1 and Zac1 loss- and gain-of
function presented as phenocopies, and overexpression of Pac1 rescued the Zac1
knockdown neuronal migration phenotype. Thus, dysregulated Zac1 expression has
striking consequences on neocortical development, suggesting that misexpression
of this transcription factor in the brain in certain growth disorders may
contribute to neurocognitive deficits. Significance statement: Altered expression
of imprinted genes is linked to cognitive dysfunction and neuropsychological
disorders, such as Angelman and Prader-Willi syndromes, and autism spectrum
disorder. Mouse models have also revealed the importance of imprinting for brain
development, with chimeras generated with parthenogenetic (two maternal
chromosomes) or androgenetic (two paternal chromosomes) cells displaying altered
brain sizes and cellular defects. Despite these striking phenotypes, only a
handful of imprinted genes are known or suspected to regulate brain development
(e.g., Dlk1, Peg3, Ube3a, necdin, and Grb10). Herein we show that the maternally
imprinted gene Zac1 is a critical regulator of neocortical development. Our
studies are relevant because loss of 6q24 maternal imprinting in humans results
in elevated ZAC1 expression, which has been associated with neurocognitive
defects.
PMID- 26424891
TI - Tonic Local Brain Blood Flow Control by Astrocytes Independent of Phasic
Neurovascular Coupling.
AB - According to the current model of neurovascular coupling, blood flow is
controlled regionally through phasic changes in the activity of neurons and
astrocytes that signal to alter arteriole diameter. Absent in this model,
however, is how brain blood flow is tonically regulated independent of regional
changes in activity. This is important because a large fraction of brain blood
flow is required to maintain basal metabolic needs. Using two-photon fluorescence
imaging combined with patch-clamp in acute rat brain slices of sensory-motor
cortex, we demonstrate that reducing resting Ca(2+) in astrocytes with
intracellular BAPTA causes vasoconstriction in adjacent arterioles. BAPTA-induced
vasoconstriction was eliminated by a general COX blocker and the effect is
mimicked by a COX-1, but not COX-2, antagonist, suggesting that astrocytes
provide tonic, steady-state vasodilation by releasing prostaglandin messengers.
Tonic vasodilation was insensitive to TTX, as well as a variety of synaptic and
extrasynaptic receptor antagonists, indicating that the phenomenon operates
largely independent of neural activity. Using in vivo two-photon fluorescence
imaging of the barrel cortex in fully awake mice, we reveal that acute COX-1
inhibition reduces resting arteriole diameter but fails to affect vasodilation in
response to vibrissae stimulation. Our findings demonstrate that astrocytes
provide tonic regulation of arterioles using resting intracellular Ca(2+) in a
manner that is independent of phasic, neuronal-evoked vasodilation. Significance
statement: The brain requires both phasic and tonic regulation of its blood
supply to service energy needs over various temporal windows. While many
mechanisms have been described for phasic blood flow regulation, how the brain
accomplishes tonic control is largely unknown. Here we describe a way in which
astrocytes contribute to the management of basal brain blood flow by providing
steady-state vasodilation to arterioles via resting astrocyte Ca(2+) and the
continuous release of prostaglandin messengers. This phenomenon may be important
for understanding the declines in basal brain blood flow that occur in aging and
dementia, as well as for the interpretation of fMRI data.
PMID- 26424890
TI - Modeling of Age-Dependent Epileptogenesis by Differential Homeostatic Synaptic
Scaling.
AB - Homeostatic synaptic plasticity (HSP) has been implicated in the development of
hyperexcitability and epileptic seizures following traumatic brain injury (TBI).
Our in vivo experimental studies in cats revealed that the severity of TBI
mediated epileptogenesis depends on the age of the animal. To characterize
mechanisms of these differences, we studied the properties of the TBI-induced
epileptogenesis in a biophysically realistic cortical network model with dynamic
ion concentrations. After deafferentation, which was induced by dissection of the
afferent inputs, there was a reduction of the network activity and upregulation
of excitatory connections leading to spontaneous spike-and-wave type seizures.
When axonal sprouting was implemented, the seizure threshold increased in the
model of young but not the older animals, which had slower or unidirectional
homeostatic processes. Our study suggests that age-related changes in the HSP
mechanisms are sufficient to explain the difference in the likelihood of seizure
onset in young versus older animals. Significance statement: Traumatic brain
injury (TBI) is one of the leading causes of intractable epilepsy. Likelihood of
developing epilepsy and seizures following severe brain trauma has been shown to
increase with age. Specific mechanisms of TBI-related epileptogenesis and how
these mechanisms are affected by age remain to be understood. We test a
hypothesis that the failure of homeostatic synaptic regulation, a slow negative
feedback mechanism that maintains neural activity within a physiological range
through activity-dependent modulation of synaptic strength, in older animals may
augment TBI-induced epileptogenesis. Our results provide new insight into
understanding this debilitating disorder and may lead to novel avenues for the
development of effective treatments of TBI-induced epilepsy.
PMID- 26424892
TI - Intracortical and Thalamocortical Connections of the Hand and Face
Representations in Somatosensory Area 3b of Macaque Monkeys and Effects of
Chronic Spinal Cord Injuries.
AB - Brains of adult monkeys with chronic lesions of dorsal columns of spinal cord at
cervical levels undergo large-scale reorganization. Reorganization results in
expansion of intact chin inputs, which reactivate neurons in the deafferented
hand representation in the primary somatosensory cortex (area 3b),
ventroposterior nucleus of the thalamus and cuneate nucleus of the brainstem. A
likely contributing mechanism for this large-scale plasticity is sprouting of
axons across the hand-face border. Here we determined whether such sprouting
takes place in area 3b. We first determined the extent of intrinsic
corticocortical connectivity between the hand and the face representations in
normal area 3b. Small amounts of neuroanatomical tracers were injected in these
representations close to the electrophysiologically determined hand-face border.
Locations of the labeled neurons were mapped with respect to the detailed
electrophysiological somatotopic maps and histologically determined hand-face
border revealed in sections of the flattened cortex stained for myelin. Results
show that intracortical projections across the hand-face border are few. In
monkeys with chronic unilateral lesions of the dorsal columns and expanded chin
representation, connections across the hand-face border were not different
compared with normal monkeys. Thalamocortical connections from the hand and face
representations in the ventroposterior nucleus to area 3b also remained unaltered
after injury. The results show that sprouting of intrinsic connections in area 3b
or the thalamocortical inputs does not contribute to large-scale cortical
plasticity. Significance statement: Long-term injuries to dorsal spinal cord in
adult primates result in large-scale somatotopic reorganization due to which chin
inputs expand into the deafferented hand region. Reorganization takes place in
multiple cortical areas, and thalamic and medullary nuclei. To what extent this
brain reorganization due to dorsal column injuries is related to axonal sprouting
is not known. Here we show that reorganization of primary somatosensory area 3b
is not accompanied with either an increase in intrinsic cortical connections
between the hand and face representations, or any change in thalamocortical
inputs to these areas. Axonal sprouting that causes reorganization likely takes
place at subthalamic levels.
PMID- 26424894
TI - Signal Propagation in the Human Visual Pathways: An Effective Connectivity
Analysis.
AB - Although the visual system has been extensively investigated, an integrated
account of the spatiotemporal dynamics of long-range signal propagation along the
human visual pathways is not completely known or validated. In this work, we used
dynamic causal modeling approach to provide insights into the underlying neural
circuit dynamics of pattern reversal visual-evoked potentials extracted from
concurrent EEG-fMRI data. A recurrent forward-backward connectivity model,
consisting of multiple interacting brain regions identified by EEG source
localization aided by fMRI spatial priors, best accounted for the data dynamics.
Sources were first identified in the thalamic area, primary visual cortex, as
well as higher cortical areas along the ventral and dorsal visual processing
streams. Consistent with hierarchical early visual processing, the model
disclosed and quantified the neural temporal dynamics across the identified
activity sources. This signal propagation is dominated by a feedforward process,
but we also found weaker effective feedback connectivity. Using effective
connectivity analysis, the optimal dynamic causal modeling revealed enhanced
connectivity along the dorsal pathway but slightly suppressed connectivity along
the ventral pathway. A bias was also found in favor of the right hemisphere
consistent with functional attentional asymmetry. This study validates, for the
first time, the long-range signal propagation timing in the human visual
pathways. A similar modeling approach can potentially be used to understand other
cognitive processes and dysfunctions in signal propagation in neurological and
neuropsychiatric disorders. Significance statement: An integrated account of long
range visual signal propagation in the human brain is currently incomplete. Using
computational neural modeling on our acquired concurrent EEG-fMRI data under a
visual evoked task, we found not only a substantial forward propagation toward
"higher-order" brain regions but also a weaker backward propagation. Asymmetry in
our model's long-range connectivity accounted for the various observed activity
biases. Importantly, the model disclosed the timing of signal propagation across
these connectivity pathways and validates, for the first time, long-range signal
propagation in the human visual system. A similar modeling approach could be used
to identify neural pathways for other cognitive processes and their dysfunctions
in brain disorders.
PMID- 26424893
TI - The Cancer Chemotherapeutic Paclitaxel Increases Human and Rodent Sensory Neuron
Responses to TRPV1 by Activation of TLR4.
AB - Peripheral neuropathy is dose limiting in paclitaxel cancer chemotherapy and can
result in both acute pain during treatment and chronic persistent pain in cancer
survivors. The hypothesis tested was that paclitaxel produces these adverse
effects at least in part by sensitizing transient receptor potential vanilloid
subtype 1 (TRPV1) through Toll-like receptor 4 (TLR4) signaling. The data show
that paclitaxel-induced behavioral hypersensitivity is prevented and reversed by
spinal administration of a TRPV1 antagonist. The number of TRPV1(+) neurons is
increased in the dorsal root ganglia (DRG) in paclitaxel-treated rats and is
colocalized with TLR4 in rat and human DRG neurons. Cotreatment of rats with
lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS
RS), a TLR4 inhibitor, prevents the increase in numbers of TRPV1(+) neurons by
paclitaxel treatment. Perfusion of paclitaxel or the archetypal TLR4 agonist LPS
activated both rat DRG and spinal neurons directly and produced acute
sensitization of TRPV1 in both groups of cells via a TLR4-mediated mechanism.
Paclitaxel and LPS sensitize TRPV1 in HEK293 cells stably expressing human TLR4
and transiently expressing human TRPV1. These physiological effects also are
prevented by LPS-RS. Finally, paclitaxel activates and sensitizes TRPV1 responses
directly in dissociated human DRG neurons. In summary, TLR4 was activated by
paclitaxel and led to sensitization of TRPV1. This mechanism could contribute to
paclitaxel-induced acute pain and chronic painful neuropathy. Significance
statement: In this original work, it is shown for the first time that paclitaxel
activates peripheral sensory and spinal neurons directly and sensitizes these
cells to transient receptor potential vanilloid subtype 1 (TRPV1)-mediated
capsaicin responses via Toll-like receptor 4 (TLR4) in multiple species. A direct
functional interaction between TLR4 and TRPV1 is shown in rat and human dorsal
root ganglion neurons, TLR4/TRPV1-coexpressing HEK293 cells, and in both rat and
mouse spinal cord slices. Moreover, this is the first study to show that this
interaction plays an important role in the generation of behavioral
hypersensitivity in paclitaxel-related neuropathy. The key translational
implications are that TLR4 and TRPV1 antagonists may be useful in the prevention
and treatment of chemotherapy-induced peripheral neuropathy in humans.
PMID- 26424895
TI - Trace Fear Conditioning Differentially Modulates Intrinsic Excitability of Medial
Prefrontal Cortex-Basolateral Complex of Amygdala Projection Neurons in
Infralimbic and Prelimbic Cortices.
AB - Neuronal activity in medial prefrontal cortex (mPFC) is critical for the
formation of trace fear memory, yet the cellular mechanisms underlying these
memories remain unclear. One possibility involves the modulation of intrinsic
excitability within mPFC neurons that project to the basolateral complex of
amygdala (BLA). The current study used a combination of retrograde labeling and
in vitro whole-cell patch-clamp recordings to examine the effect of trace fear
conditioning on the intrinsic excitability of layer 5 mPFC-BLA projection neurons
in adult rats. Trace fear conditioning significantly enhanced the intrinsic
excitability of regular spiking infralimbic (IL) projection neurons, as evidenced
by an increase in the number of action potentials after current injection. These
changes were also associated with a reduction in spike threshold and an increase
in h current. In contrast, trace fear conditioning reduced the excitability of
regular spiking prelimbic (PL) projection neurons, through a learning-related
decrease of input resistance. Interestingly, the amount of conditioned freezing
was (1) positively correlated with excitability of IL-BLA projection neurons
after conditioning and (2) negatively correlated with excitability of PL-BLA
projection neurons after extinction. Trace fear conditioning also significantly
enhanced the excitability of burst spiking PL-BLA projection neurons. In both
regions, conditioning-induced plasticity was learning specific (observed in
conditioned but not in pseudoconditioned rats), flexible (reversed by
extinction), and transient (lasted <10 d). Together, these data suggest that
intrinsic plasticity within mPFC-BLA projection neurons occurs in a subregion-
and cell-type-specific manner during acquisition, consolidation, and extinction
of trace fear conditioning. Significance statement: Frontal lobe-related function
is vital for a variety of important behaviors, some of which decline during
aging. This study involves a novel combination of electrophysiological recordings
from fluorescently labeled mPFC-to-amygdala projection neurons in rats with
acquisition and extinction of trace fear conditioning to determine how specific
neurons change during behavior. This is the first study to demonstrate that trace
fear conditioning significantly alters the intrinsic excitability of mPFC-to
amygdala projection neurons in a subregion- and cell-type-specific manner, which
is also transient and reversed by extinction. These data are of broad interest to
the neuroscientific community, and the results will inspire additional studies
investigating the cellular mechanisms underlying circuit-specific changes within
the brain as a result of associative learning and memory.
PMID- 26424897
TI - Subthalamic nucleus stimulation improves Parkinson's disease-associated
camptocormia in parallel to its preoperative levodopa responsiveness.
AB - OBJECTIVE: The aim of this work was to identify factors predictive of
postoperative improvement of camptocormia in patients with Parkinson's disease
(PD) treated by subthalamic nucleus (STN) stimulation. BACKGROUND: Camptocormia,
one of the most disabling features of PD, often responds poorly to medical
therapies. The reported effects of deep brain stimulation on PD-associated
camptocormia vary, and preoperative characteristics affecting the surgical
outcome remain unclear. METHODS: We evaluated 17 patients with camptocormia whose
preoperative off-medication thoracolumbar angle exceeded 45 degrees . We used
photographs to measure their thoracolumbar angle preoperatively, 3 months after
surgery, and at the last follow-up (mean 36.5 months postoperatively) in status
on-medication and off-medication. The patient age, duration of PD and
camptocormia, daily medications, Unified Parkinson's Disease Rating Scale (UPDRS)
subscores and the Schwab-England activity of daily living scale (S-E) were also
recorded. Univariate analysis was performed to identify factors predictive of the
postoperative improvement of camptocormia. RESULTS: STN stimulation significantly
improved the UPDRS subscores and S-E, and resulted in a reduction of daily
medications 3 months post-treatment. The preoperative thoracolumbar angle (mean+/
SD) in status off-medication (84.0+/-29.5 degrees ) was significantly ameliorated
3 months postoperatively (49.8+/-29.3 degrees ) and at the last follow-up (54.8+/
28.3 degrees ). There was no correlation between the postoperative camptocormia
improvement rate and preoperative parameters other than the duration and severity
of camptocormia and the levodopa responsiveness of the thoracolumbar angle.
Symptom duration negatively affected levodopa responsiveness. CONCLUSIONS: STN
stimulation improves PD-associated camptocormia in parallel with preoperative
levodopa responsiveness. Long symptom duration interferes with levodopa
responsiveness.
PMID- 26424896
TI - TRPV4 and AQP4 Channels Synergistically Regulate Cell Volume and Calcium
Homeostasis in Retinal Muller Glia.
AB - Brain edema formation occurs after dysfunctional control of extracellular volume
partly through impaired astrocytic ion and water transport. Here, we show that
such processes might involve synergistic cooperation between the glial water
channel aquaporin 4 (AQP4) and the transient receptor potential isoform 4
(TRPV4), a polymodal swelling-sensitive cation channel. In mouse retinas, TRPV4
colocalized with AQP4 in the end feet and radial processes of Muller astroglia.
Genetic ablation of TRPV4 did not affect the distribution of AQP4 and vice versa.
However, retinas from Trpv4(-/-) and Aqp4(-/-) mice exhibited suppressed
transcription of genes encoding Trpv4, Aqp4, and the Kir4.1 subunit of inwardly
rectifying potassium channels. Swelling and [Ca(2+)]i elevations evoked in Muller
cells by hypotonic stimulation were antagonized by the selective TRPV4 antagonist
HC-067047 (2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3
(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide) or Trpv4 ablation. Elimination
of Aqp4 suppressed swelling-induced [Ca(2+)]i elevations but only modestly
attenuated the amplitude of Ca(2+) signals evoked by the TRPV4 agonist
GSK1016790A [(N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3
hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2
carboxamide]. Glial cells lacking TRPV4 but not AQP4 showed deficits in hypotonic
swelling and regulatory volume decrease. Functional synergy between TRPV4 and
AQP4 during cell swelling was confirmed in the heterologously expressing Xenopus
oocyte model. Importantly, when the swelling rate was osmotically matched for
AQP4-positive and AQP4-negative oocytes, TRPV4 activation became independent of
AQP4. We conclude that AQP4-mediated water fluxes promote the activation of the
swelling sensor, whereas Ca(2+) entry through TRPV4 channels reciprocally
modulates volume regulation, swelling, and Aqp4 gene expression. Therefore, TRPV4
AQP4 interactions constitute a molecular system that fine-tunes astroglial volume
regulation by integrating osmosensing, calcium signaling, and water transport
and, when overactivated, triggers pathological swelling. Significance statement:
We characterize the physiological features of interactions between the astroglial
swelling sensor transient receptor potential isoform 4 (TRPV4) and the aquaporin
4 (AQP4) water channel in retinal Muller cells. Our data reveal an elegant and
complex set of mechanisms involving reciprocal interactions at the level of glial
gene expression, calcium homeostasis, swelling, and volume regulation.
Specifically, water influx through AQP4 drives calcium influx via TRPV4 in the
glial end foot, which regulates expression of Aqp4 and Kir4.1 genes and
facilitates the time course and amplitude of hypotonicity-induced swelling and
regulatory volume decrease. We confirm the crucial facets of the signaling
mechanism in heterologously expressing oocytes. These results identify the
molecular mechanism that contributes to dynamic regulation of glial volume but
also provide new insights into the pathophysiology of glial reactivity and edema
formation.
PMID- 26424898
TI - Bilateral adaptive deep brain stimulation is effective in Parkinson's disease.
AB - INTRODUCTION & OBJECTIVES: Adaptive deep brain stimulation (aDBS) uses feedback
from brain signals to guide stimulation. A recent acute trial of unilateral aDBS
showed that aDBS can lead to substantial improvements in contralateral hemibody
Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and may be superior
to conventional continuous DBS in Parkinson's disease (PD). We test whether
potential benefits are retained with bilateral aDBS and in the face of concurrent
medication. METHODS: We applied bilateral aDBS in 4 patients with PD undergoing
DBS of the subthalamic nucleus. aDBS was delivered bilaterally with independent
triggering of stimulation according to the amplitude of beta activity at the
corresponding electrode. Mean stimulation voltage was 3.0+/-0.1 volts. Motor
assessments consisted of double-blinded video-taped motor UPDRS scores that
included both limb and axial features. RESULTS: UPDRS scores were 43% (p=0.04;
Cohen's d=1.62) better with aDBS than without stimulation. Motor improvement with
aDBS occurred despite an average time on stimulation (ToS) of only 45%. Levodopa
was well tolerated during aDBS and led to further reductions in ToS. CONCLUSION:
Bilateral aDBS can improve both axial and limb symptoms and can track the need
for stimulation across drug states.
PMID- 26424900
TI - Stress Concentration of Periodic Collinear Square Holes in an Infinite Plate in
Tension.
AB - A numerical approach for the stress concentration of periodic collinear holes in
an infinite plate in tension is presented. It involves the fictitious stress
method and a generalization of Bueckner's principle. Numerical examples are
concluded to show that the numerical approach is very efficient and accurate for
analyzing the stress concentration of periodic collinear holes in an infinite
plate in tension. The stress concentration of periodic collinear square holes in
an infinite plate in tension is studied in detail by using the numerical
approach. The calculated stress concentration factor is proven to be accurate.
PMID- 26424899
TI - Heat Transfer in Health and Healing.
AB - Our bodies depend on an exquisitely sensitive and refined temperature control
system to maintain a state of health and homeostasis. The exceptionally broad
range of physical activities that humans engage in and the diverse array of
environmental conditions we face require remarkable strategies and mechanisms for
regulating internal and external heat transfer processes. On the occasions for
which the body suffers trauma, therapeutic temperature modulation is often the
approach of choice for reversing injury and inflammation and launching a cascade
of healing. The focus of human thermoregulation is maintenance of the body core
temperature within a tight range of values, even as internal rates of energy
generation may vary over an order of magnitude, environmental convection, and
radiation heat loads may undergo large changes in the absence of any significant
personal control, surface insulation may be added or removed, all occurring while
the body's internal thermostat follows a diurnal circadian cycle that may be
altered by illness and anesthetic agents. An advanced level of understanding of
the complex physiological function and control of the human body may be combined
with skill in heat transfer analysis and design to develop life-saving and injury
healing medical devices. This paper will describe some of the challenges and
conquests the author has experienced related to the practice of heat transfer for
maintenance of health and enhancement of healing processes.
PMID- 26424901
TI - A Novel Screening and Diagnostic Tool for Child and Adolescent Psychiatric
Disorders for Telepsychiatry.
AB - BACKGROUND: A diagnostic tool designed as part of a telepsychiatry application
for diagnosis and management of child and adolescent psychiatric disorders in
India was developed considering the paucity of trained child psychiatrists and
mental health professionals in India. MATERIALS AND METHODS: The diagnostic tool
consisted of screening and 10(th) revision of the International Statistical
Classification of Diseases and Related Health Problems (ICD-10) criteria-based
diagnostic algorithms for 18 psychiatric disorders seen in childhood and
adolescence. Accuracy of diagnoses and feasibility of use of the tool was
examined by comparing it with detailed semi-structured clinical evaluations by a
qualified psychiatrist with 50 psychiatric patients (children and adolescents).
STATISTICAL ANALYSIS: Descriptive analyses and paired t-tests were conducted to
compare the mean number of diagnosis generated by the two interviews.
Sensitivity, specificity, positive and negative predictive values were computed
for the screening and the diagnostic sub-modules of the tool, compared to the
clinical diagnoses. Kappa coefficients were computed to assess agreement between
the diagnoses generated by the diagnostic sub-module and the clinical diagnoses.
RESULTS: The screening sub-module had high sensitivity, high specificity and
negative predictive values for all disorders. For the diagnostic sub-module,
there was moderate (kappa-0.4-0.6) to substantial agreement (kappa > 0.6) for all
the disorders, (except psychosis) and high sensitivity (barring a few disorders)
and specificity for almost all the disorders. Positive predictive values were
found to be acceptable to high for most disorders, with consistently high
negative predictive values. CONCLUSION: The new tool was found to be
comprehensive, reasonably short and feasible. Results showed acceptable level of
accuracy in diagnosis generated by the tool.
PMID- 26424902
TI - Clinical Significance of SASH1 Expression in Glioma.
AB - OBJECTIVE: SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor
suppressor gene. The role of SASH1 in glioma has not yet been described. We
investigated SASH1 expression in glioma cases to determine its clinical
significance on glioma pathogenesis and prognosis. METHODS: We produced tissue
microarrays using 121 patient-derived glioma samples and 30 patient-derived
nontumor cerebral samples. Immunohistochemistry and Western blotting were used to
evaluate SASH1 expression. We used Fisher's exact tests to determine
relationships between SASH1 expression and clinicopathological characteristics;
Cox regression analysis to evaluate the independency of different SASH1
expression; Kaplan-Meier analysis to determine any correlation of SASH1
expression with survival rate. RESULTS: SASH1 expression was closely correlated
with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were
mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly
grades I-II. Kaplan-Meier analysis revealed a significant positive correlation
between SASH1 expression and postoperative survival. CONCLUSIONS: SASH1 was
widely expressed in normal and low-grade glioma tissues. SASH1 expression
strongly correlated with glioma grades, showing higher expression at a lower
grade, which decreased significantly as grade increased. Furthermore, SASH1
expression was positively correlated with better postoperative survival in
patients with glioma.
PMID- 26424903
TI - Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High
Grade Human Brain Tumors.
AB - OBJECTIVES: Glucose metabolism outside of oxidative phosphorylation, or aerobic
glycolysis (AG), is a hallmark of active cancer cells that is not directly
measured with standard (18)F-fluorodeoxyglucose (FDG) positron emission
tomography (PET). In this study, we characterized tumor regions with elevated AG
defined based on PET measurements of glucose and oxygen metabolism. METHODS:
Fourteen individuals with high-grade brain tumors underwent structural MR scans
and PET measurements of cerebral blood flow (CBF), oxygen (CMRO2) and glucose
(CMRGlu) metabolism, and AG, using (15)O-labeled CO, O2 and H2O, and FDG, and
were compared to a normative cohort of 20 age-matched individuals. RESULTS:
Elevated AG was observed in most high-grade brain tumors and it was associated
with decreased CMRO2 and CBF, but not with significant changes in CMRGlu.
Elevated AG was a dramatic and early sign of tumor growth associated with
decreased survival. AG changes associated with tumor growth were differentiated
from the effects of nonneoplastic processes such as epileptic seizures.
CONCLUSIONS: Our findings demonstrate that high-grade brain tumors exhibit
elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas
of active tumor growth that are not evident on conventional FDG PET.
PMID- 26424904
TI - Exploring Discrimination and Mental Health Disparities Faced By Black Sexual
Minority Women Using a Minority Stress Framework.
AB - Black sexual minority women are triply marginalized due to their race, gender,
and sexual orientation. We compared three dimensions of discrimination-frequency
(regularity of occurrences), scope (number of types of discriminatory acts
experienced), and number of bases (number of social statuses to which
discrimination was attributed)-and self-reported mental health (depressive
symptoms, psychological well-being, and social well-being) between 64 Black
sexual minority women and each of two groups sharing two of three marginalized
statuses: (a) 67 White sexual minority women and (b) 67 Black sexual minority
men. Black sexual minority women reported greater discrimination frequency,
scope, and number of bases and poorer psychological and social well-being than
White sexual minority women and more discrimination bases, a higher level of
depressive symptoms, and poorer social well-being than Black sexual minority men.
We then tested and contrasted dimensions of discrimination as mediators between
social status (race or gender) and mental health outcomes. Discrimination
frequency and scope mediated the association between race and mental health, with
a stronger effect via frequency among sexual minority women. Number of
discrimination bases mediated the association between gender and mental health
among Black sexual minorities. Future research and clinical practice would
benefit from considering Black sexual minority women's mental health in a
multidimensional minority stress context.
PMID- 26424905
TI - Association of increased rate of condemnation of broiler carcasses due to hepatic
abnormalities with immunosuppressive diseases in the broiler chicken industry in
Saskatchewan.
AB - The objective of this study was to identify the causative agents of hepatitis
observed in broiler chickens at processing. Livers of chickens from 16 broiler
farms in Saskatchewan with gross lesions of hepatitis were collected at
processing. In addition to routine bacterial isolation and histopathological
examination, serologic studies for infectious bursal disease virus (IBDV) and
Chicken anaemia virus (CAV), calculation of the ratio of the weight of the bursa
of Fabricius (BF) to body weight (BBW), and histopathological examination of the
BF were done. Of the 264 livers with gross lesions, 83% had multifocal to
coalescing necrotizing hepatitis, 16% had perihepatitis, and 1% had hemorrhages.
No definitive causative microorganisms were isolated from the hepatic lesions;
however, no significant bacterial isolations were made. Bursal atrophy, low BBW
ratio, and high titer of antibody against IBDV each correlated with the rate of
total condemnations (P = 0.0188, P = 0.0001, and P = 0.0073, respectively).
Nucleotide sequencing of IBDV isolated from the BF identified the variant strains
Delaware-E and 586. Condemnation because of hepatic lesions was correlated with
titer of antibody against IBDV and BBW (P = 0.016 and P = 0.027). The results of
this study demonstrate that hepatic lesions in Saskatchewan chickens are not
currently caused by a primary bacterial pathogen but are associated with
indicators of immunosuppression that is likely due to variant IBDV.
PMID- 26424906
TI - Descriptive analysis and spatial epidemiology of porcine reproductive and
respiratory syndrome (PRRS) for swine sites participating in area regional
control and elimination programs from 3 regions of Ontario.
AB - The objectives of this study were to describe demographics, basic biosecurity
practices, ownership structure, and prevalence of porcine reproductive and
respiratory syndrome (PRRS) in swine sites located in 3 regions in Ontario, and
investigate the presence of spatial clustering and clusters of PRRS positive
sites in the 3 regions. A total of 370 swine sites were enrolled in Area Regional
Control and Elimination projects in Niagara, Watford, and Perth from 2010 to
2013. Demographics, biosecurity, and site ownership data were collected using a
standardized questionnaire and site locations were obtained from an industry
organization. Status was assigned on the basis of available diagnostic tests
and/or assessment by site veterinarians. Spatial dependence was investigated
using the D-function, the spatial scan statistic test and the spatial relative
risk method. Results showed that the use of strict all-in all-out (AIAO) pig flow
and shower before entry are uncommon biosecurity practices in swine sites, but a
larger proportion of sites reported having a Danish entry. The prevalence of PRRS
in the 3 regions ranged from 17% to 48% and localized high and low risk clusters
were detected. Sites enrolled in the PRRS control projects were characterized by
membership in multiple and overlapping ownership structures and networks, which
complicates the way the results of monitoring and disease management measures are
communicated to the target population.
PMID- 26424907
TI - Streptococcus suis in employees and the environment of swine slaughterhouses in
Sao Paulo, Brazil: Occurrence, risk factors, serotype distribution, and
antimicrobial susceptibility.
AB - Streptococcus suis is an important pathogen in the swine industry. This article
is the first to report the occurrence, risk factors, serotype distribution, and
antimicrobial susceptibility of S. suis recovered from employees and
environmental samples of swine slaughterhouses in Brazil. Tonsillar swabs from
all 139 pig-slaughtering employees and 261 environmental swabs were collected for
detection of S. suis and serotyping by monoplex and multiplex polymerase chain
reaction, respectively. Antimicrobial susceptibility was determined by the disk
diffusion method. Although S. suis was not detected in any of the tested
employees, it was isolated from 25% of the environmental samples. Significant
differences (P < 0.05) in the occurrence of S. suis were observed between
slaughterhouses and between areas of low, medium, and high risk. The most
frequent serotypes were 4 and 29, each accounting for 12% of the isolates,
followed by 5, 12, 21, and 31, each accounting for 6%. High rates of
susceptibility to the antimicrobials doxycycline (100%), ceftiofur (94%),
ampicillin (81%), and cephalexin (75%) were observed. However, multidrug
resistance was observed in all the isolates. Because S. suis is present in the
environment of swine slaughterhouses, on carcasses and knives, as well as on the
hands of employees in all areas, all employees are at risk of infection.
PMID- 26424908
TI - Antimicrobial effect against different bacterial strains and bacterial adaptation
to essential oils used as feed additives.
AB - The aim of this study was to evaluate the antimicrobial activity and determine
the minimum bactericidal concentration (MBC) of the essential oils derived from
Origanum vulgare (oregano), Melaleuca alternifolia (tea tree), Cinnamomum cassia
(cassia), and Thymus vulgaris (white thyme) against Salmonella Typhimurium,
Salmonella Enteritidis, Escherichia coli, Staphylococcus aureus and Enterococcus
faecalis. The study also investigated the ability of these different bacterial
strains to develop adaptation after repetitive exposure to sub-lethal
concentrations of these essential oils. The MBC of the essential oils studied was
determined by disc diffusion and broth dilution methods. All essential oils
showed antimicrobial effect against all bacterial strains. In general, the
development of adaptation varied according to the bacterial strain and the
essential oil (tea tree > white thyme > oregano). Therefore, it is important to
use essential oils at efficient bactericidal doses in animal feed, food, and
sanitizers, since bacteria can rapidly develop adaptation when exposed to sub
lethal concentrations of these oils.
PMID- 26424909
TI - Prevalence of internal parasites in beef cows in the United States: Results of
the National Animal Health Monitoring System's (NAHMS) beef study, 2007-2008.
AB - During the United States Department of Agriculture (USDA) National Animal Health
Monitoring System's (NAHMS) 2007-2008 beef study, 567 producers from 24 US States
were offered the opportunity to collect fecal samples from weaned beef calves and
have them evaluated for the presence of parasite eggs (Phase 1). Participating
producers were provided with instructions and materials for sample collection. Up
to 20 fresh fecal samples were collected from each of the 99 participating
operations. Fresh fecal samples were submitted to one of 3 randomly assigned
laboratories for evaluation. Upon arrival at the laboratories, all samples were
processed for the enumeration of strongyle, Nematodirus, and Trichuris eggs using
the modified Wisconsin technique. The presence or absence of coccidian oocysts
and tapeworm eggs was also noted. In submissions where the strongyle eggs per
gram exceeded 30, aliquots from 2 to 6 animals were pooled for DNA extraction.
Extracted DNA was subjected to genus level polymerase chain reaction (PCR)
identification for the presence of Ostertagia, Cooperia, Haemonchus,
Oesophagostomum, and Trichostrongylus. In this study, 85.6% of the samples had
strongyle type, Nematodirus, and Trichuris eggs. Among the samples evaluated, 91%
had Cooperia, 79% Ostertagia, 53% Haemonchus, 38% Oesophagostomum, 18%
Nematodirus, 7% Trichuris, and 3% Trichostrongylus. The prevalence of coccidia
and tapeworm eggs was 59.9% and 13.7%, respectively.
PMID- 26424910
TI - Effectiveness of current anthelmintic treatment programs on reducing fecal egg
counts in United States cow-calf operations.
AB - During the United States Department of Agriculture (USDA) National Animal Health
Monitoring System's (NAHMS) 2007-2008 beef study, producers from 24 states were
offered the opportunity to evaluate their animals for internal parasites and for
overall responses to treatment with anthelmintics. A lapse of 45 d was required
between initial sampling and any previous treatments. Choice of anthelmintic
(oral benzimidazoles, and both injectable and pour-on endectocides) was at the
discretion of the producer so as not to alter the local control programs. Fresh
fecal samples were collected from 20 animals, or from the entire group if less
than 20, then randomly assigned to 1 of 3 participating laboratories for
examination. Analyses consisted of double centrifugation flotation followed by
enumeration of strongyle, Nematodirus, and Trichuris eggs (the presence of
coccidian oocysts and tapeworm eggs was also noted). Where strongyle eggs per
gram (epg) exceeded 30, aliquots from 2 to 6 animals were pooled for egg
isolation and polymerase chain reaction (PCR) analysis for the presence of
Ostertagia, Cooperia, Haemonchus, Oesophagostomum, and Trichostrongylus. Results
from 72 producers (19 States) indicated that fecal egg count reductions were <
90% in 1/3 of the operations. All operations exhibiting less than a 90% reduction
had used pour-on macrocyclic lactones as the anthelmintic treatment. While some
of these less than expected reductions could have been the result of improper
drug application, PCR analyses of the parasite populations surviving treatment,
coupled with follow-up studies at a limited number of sites, indicated that less
than expected reductions were most likely due to anthelmintic resistance in
Cooperia spp. and possibly Haemonchus spp.
PMID- 26424911
TI - Efficacy of a topical bovine-derived thrombin solution as a hemostatic agent in a
rodent model of hepatic injury.
AB - Hemorrhage is a major concern in patients undergoing hepatic surgery or in those
with hepatic trauma. In these cases, employing traditional hemostatic strategies
can be problematic due to the diffuse nature of hepatic hemorrhage and limited
opportunities for direct hemostasis. This study assessed the efficacy of a bovine
derived thrombin solution, (BT), as a topical liquid agent to augment hemostasis
and survival following severe hepatic hemorrhage in a rat model. Heart rate (HR),
arterial blood pressure (ABP), packed cell volume (PCV), and overall survival
were evaluated in 54 rats randomly assigned to receive topical application of BT,
saline, or suture ligation applied immediately to a liver lobe following
controlled laceration. Six additional rats received liver laceration with no
applied treatment. Intravenous fluid resuscitation was initiated and HR and ABP
were recorded for 60 min, after which survivors were recovered from anesthesia.
Rats were then monitored for 72 h, after which survivors were euthanized. There
was no significant difference in survival time, percentage survival, intra
operative ABP or HR, or post-operative PCV between treatment groups. There is
insufficient evidence to recommend BT as the sole therapy using this delivery
method for mitigating severe hemorrhage from liver injury.
PMID- 26424912
TI - Hemodynamic effects of target-controlled infusion of propofol alone or in
combination with a constant-rate infusion of remifentanil in dogs.
AB - The objective of this study was to evaluate the hemodynamic effects of target
controlled infusion (TCI) of propofol alone or in combination with a constant
rate infusion (CRI) of remifentanil. Six adult dogs were given 2 treatments in a
randomized crossover study with a 7-day interval between treatments. Treatment 1
was propofol (P) and treatment 2 was propofol and remifentanil (P-Rem), without
any premedication. Propofol was induced using a TCI system with a predicted
plasma concentration (Cp) of 6.0 MUg/mL. Anesthesia was maintained within the Cp
range (0.65 to 3.0 MUg/mL) for 120 min and remifentanil was administered at a
rate of 0.3 MUg/kg body weight (BW) per minute, CRI. Cardiopulmonary variables
were recorded before (baseline), during, and 120 min after drug administration.
Heart rate (HR) decreased significantly in the P-Rem group (46%) compared with
baseline values. In the P-Rem group, the cardiac index (CI) decreased
significantly (49% to 58%) and the stroke volume (SV) decreased compared with
baseline values. The systemic vascular resistance index (SVRI) increased
significantly in the P-Rem group compared with baseline values. There was no
difference in mean arterial pressure (MAP) between the groups. Central venous
pressure (CVP) and pulmonary artery occlusion pressure (PAOP) significantly
increased in the P-Rem group compared with baseline values. In conclusion, the
hemodynamic changes observed in this study indicate a compromise of the
cardiovascular system, although the dogs in this study were healthy/euvolemic and
there was no change in preload. More studies are required in order to evaluate
the actual safety of the combination of propofol and remifentanil in patients
with reduced cardiac reserve.
PMID- 26424913
TI - Use of ImageJ software for histomorphometric evaluation of normal and severely
affected canine ear canals.
AB - Morphological studies comparing normal and diseased ear canals use primarily
subjective scoring. The aim of this study was to compare normal and severely
affected ears in dogs with objective measurements using ImageJ software. Ear
canals were harvested from cadavers with normal ears and from dogs that underwent
total ear canal ablation for unresolved otitis. Histopathology samples from ear
canals were evaluated by semi-quantitative scoring and also by using ImageJ
software for histomorphometric measurements. The normal ears were compared to the
severely affected ears using the 2 methods. The 2 methods were significantly (P <
0.0001) correlated for epidermal hyperplasia, ceruminous gland dilation, and
hyperplasia and tissue inflammation, which were significantly greater in the
severely affected ears (P < 0.0001). This study demonstrated that there is a very
high correlation between the 2 methods for the most markedly affected components
of otitis externa and that ImageJ software can be efficiently used to measure and
evaluate ear canal histomorphometry.
PMID- 26424914
TI - Comparative study of 2 surgical techniques for castration of guinea pigs (Cavia
porcellus).
AB - The objective of this study was to compare 2 surgical approaches (scrotal or
abdominal) for castration of guinea pigs and to investigate post-operative
infection rates with either technique. Forty-eight guinea pigs were castrated by
scrotal or abdominal technique after being randomly assigned to 1 of 2 groups (n
= 24). Individuals were either castrated by an experienced exotic animal surgeon
(n = 12) or by an experienced small animal surgeon (n = 12). Surgical wounds were
evaluated daily before euthanasia for histological evaluation 2 wks after
surgery. Post-operative infection rate was significantly higher in the scrotal
group than in the abdominal group, with a higher rate for the experienced small
animal surgeon. Castration of guinea pigs with the abdominal technique is
significantly faster and has a significantly lower post-operative infection rate
than the scrotal technique.
PMID- 26424915
TI - Relationship of oxidative stress in skeletal muscle with obesity and obesity
associated hyperinsulinemia in horses.
AB - In horses, hyperinsulinemia and insulin resistance (insulin dysregulation) are
associated with the development of laminitis. Although obesity is associated with
insulin dysregulation, the mechanism of obesity-associated insulin dysregulation
remains to be established. We hypothesized that oxidative stress in skeletal
muscle is associated with obesity-associated hyperinsulinemia in horses. Thirty
five light breed horses with body condition scores (BCS) of 3/9 to 9/9 were
studied, including 7 obese, normoinsulinemic (BCS >= 7, resting serum insulin <
30 MUIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin >= 30 MUIU/mL)
horses. Markers of oxidative stress (oxidative damage, mitochondrial function,
and antioxidant capacity) were evaluated in skeletal muscle biopsies. A
Spearman's rank correlation coefficient was used to determine relationships
between markers of oxidative stress and BCS. Furthermore, to assess the role of
oxidative stress in obesity-related hyperinsulinemia, markers of antioxidant
capacity and oxidative damage were compared among lean, normoinsulinemic (L-NI);
obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses.
Increasing BCS was associated with an increase in gene expression of a
mitochondrial protein responsible for mitochondrial biogenesis (estrogen-related
receptor alpha, ERRalpha) and with increased antioxidant enzyme total superoxide
dismutase (TotSOD) activity. When groups (L-NI, O-NI, and O-HI) were compared,
TotSOD activity was increased and protein carbonyls, a marker of oxidative
damage, decreased in the O-HI compared to the L-NI horses. These findings suggest
that a protective antioxidant response occurred in the muscle of obese animals
and that obesity-associated oxidative damage in skeletal muscle is not central to
the pathogenesis of equine hyperinsulinemia.
PMID- 26424916
TI - Identification of immunodominant proteins from Mannheimia haemolytica and
Histophilus somni by an immunoproteomic approach.
AB - Mannheimia haemolytica and Histophilus somni are frequently isolated from
diseased cattle with bovine respiratory disease (BRD). They compromise animal
lung function and the immune responses generated are not sufficient to limit
infection. Identification of specific immunogenic antigens for vaccine
development represents a great challenge. Immunogenic proteins were identified by
immunoproteomic approach with sera from cattle immunized with a commercial
cellular vaccine of M. haemolytica and H. somni. Proteins of M. haemolytica were
identified as solute ABC transporter, iron-binding protein, and hypothetical
protein of capsular biosynthesis. Histophilus somni proteins correspond to porin,
amino acid ABC transporter, hypothetical outer membrane protein, cysteine
synthase, and outer membrane protein P6. Although these antigens share strong
similarities with other proteins from animal pathogens, the ABC system proteins
have been associated with virulence and these proteins could be considered as
potential vaccine candidates for BRD.
PMID- 26424917
TI - Clonal distribution of Streptococcus suis isolated from diseased pigs in the
central region of Chile.
AB - The characteristics of 29 Chilean field strains of Streptococcus suis recovered
between 2007 and 2011 from pigs with clinical signs at different farms were
studied. Serotyping with use of the coagglutination test revealed that all but 1
strain belonged to serotype 6; the remaining strain was serotype 22. All the
serotype-6 strains were suilysin (hemolysin)-negative; in addition, they were
found to be genotypically homogeneous by enterobacterial repetitive intergenic
consensus sequence-based polymerase chain reaction (ERIC-PCR) and sensitive to
ampicillin, ceftiofur, penicillin, and trimethoprim/sulfamethoxazole. The results
indicate that, in contrast to what is generally observed in other countries, a
single clone of S. suis was isolated from diseased pigs in the central region of
Chile.
PMID- 26424919
TI - Aerobic training increases the expression of adiponectin receptor genes in the
peripheral blood mononuclear cells of young men.
AB - Little is known about the effect of exercise training on the expression of
adiponectin receptor genes in peripheral blood mononuclear cells (PBMCs). In this
study, we investigated the effects of aerobic training on the expression of
AdipoR1 and AidpoR2 mRNAs in PBMCs, whole body insulin sensitivity, and
circulating adiponectins in men. Thirty young men were randomly assigned to
either a control (n=15) or an exercise (n=15) group. Subjects assigned to the
exercise group underwent a 12-week jogging and/or running programme on a motor
driven treadmill at an intensity of 60%-75% of the age-based maximum heart rate
with duration of 40 minutes per session and a frequency of 5 days per week. Two
way mixed ANOVA with repeated measures was used to test any significant time-by
group interaction effects for the measured variables at p=0.05. We found
significant time-by-group interaction effects for waist circumference (p=0.001),
VO2max (p<0.001), fasting insulin (p=0.016), homeostasis model assessment for
insulin resistance (HOMA-IR) (p=0.010), area under the curve (AUC) for insulin
response during the 75-g oral glucose tolerance test (p=0.002), high-molecular
weight (HMW) adiponectin (p=0.016), and the PBMC mRNA levels of AdipoR1 (p<0.001)
and AdipoR2 (p=0.001). The exercise group had significantly increased mRNA levels
of AdipoR1 and AdipoR2 in PBMCs, along with increased whole body insulin
sensitivity and HMW adiponectin, decreased waist circumference, and increased
VO2max compared with the control group. In summary, the current findings suggest
that exercise training modulates the expression of AdipoR1 and AdipoR2 mRNAs in
PBMCs, implying that manipulation of the expression of these genes could be a
potential surrogate for lifestyle intervention-mediated improvements of whole
body insulin sensitivity and glucose homeostasis.
PMID- 26424918
TI - Enhanced inactivation of avian influenza virus at -20 degrees C by disinfectants
supplemented with calcium chloride or other antifreeze agents.
AB - Avian influenza outbreaks have occurred during winter months, and effective
disinfection of poultry premises at freezing temperatures is needed. The
commercial disinfectants Virkon and Accel, supplemented with an antifreeze agent
[propylene glycol (PG), methanol (MeOH), or calcium chloride (CaCl2)], were
evaluated for their effectiveness in killing avian influenza virus (AIV) at -20
degrees C or 21 degrees C. An AIV suspension was applied to stainless steel
disks, air-dried, and covered with a disinfectant or antifreeze agent for 5 to 30
min. Virkon (2%) and Accel (6.25%) with 30% PG, 20% MeOH, or 20% CaCl2
inactivated 6 log10 AIV within 5 min at -20 degrees C and 21 degrees C. At these
temperatures PG and MeOH alone did not kill AIV, but the 20% CaCl2 solution alone
inactivated 5 log10 AIV within 10 min. The results suggested that CaCl2 is
potentially useful to enhance the effectiveness of disinfection of poultry
facilities after outbreaks of AIV infection in warm and cold seasons.
PMID- 26424920
TI - Increased extracellular dopamine and 5-hydroxytryptamine levels contribute to
enhanced subthalamic nucleus neural activity during exhausting exercise.
AB - The purpose of the study was to explore the mechanism underlying the enhanced
subthalamic nucleus (STN) neural activity during exhausting exercise from the
perspective of monoamine neurotransmitters and changes of their corresponding
receptors. Rats were randomly divided into microdialysis and immunohistochemistry
study groups. For microdialysis study, extracellular fluid of the STN was
continuously collected with a microdialysis probe before, during and 90 min after
one bout of exhausting exercise. Dopamine (DA) and 5-hydroxytryptamine (5-HT)
levels were subsequently detected with high-performance liquid chromatography
(HPLC). For immunohistochemistry study, the expression of DRD2 and HT2C receptors
in the STN, before, immediately after and 90 min after exhaustion was detected
through immunohistochemistry technique. Microdialysis study results showed that
the extracellular DA and 5-HT neurotransmitters increased significantly
throughout the procedure of exhausting exercise and the recovery period (P<0.05
or P<0.01). Immunohistochemistry study results showed that the expression levels
of DRD2 and HT2C in the rat STN immediately after exhausting exercise and at the
time point of 90 min after exhaustion were both higher than those of the rest
condition, but the difference was not significant (P>0.05). Our results suggest
that the increased extracellular DA and 5-HT in the STN might be one important
factor leading to the enhanced STN neural activity and the development of fatigue
during exhausting exercise. This study may essentially offer useful evidence for
better understanding of the mechanism of the central type of exercise-induced
fatigue.
PMID- 26424921
TI - The effect of estrogen on muscle damage biomarkers following prolonged aerobic
exercise in eumenorrheic women.
AB - This study assessed the influence of estrogen (E2) on muscle damage biomarkers
[skeletal muscle - creatine kinase (CK); cardiac muscle - CK-MB] responses to
prolonged aerobic exercise. Eumenorrheic women (n=10) who were physically active
completed two 60-minute treadmill running sessions at ~60-65% maximal intensity
during low E2 (midfollicular menstrual phase) and high E2 (midluteal menstrual
phase) hormonal conditions. Blood samples were collected prior to exercise
(following supine rest), immediately post-, 30 min post-, and 24 hours post
exercise to determine changes in muscle biomarkers. Resting blood samples
confirmed appropriate E2 hormonal levels Total CK concentrations increased
following exercise and at 24 hours post-exercise were higher in the midfollicular
low E2 phase (p<0.001). However, CK-MB concentrations were unaffected by E2 level
or exercise (p=0.442) resulting in the ratio of CK-MB to total CK being
consistently low in subject responses (i.e., indicative of skeletal muscle
damage). Elevated E2 levels reduce the CK responses of skeletal muscle, but had
no effect on CK-MB responses following prolonged aerobic exercise. These findings
support earlier work showing elevated E2 is protective of skeletal muscle from
exercise-induced damage associated with prolonged aerobic exercise.
PMID- 26424922
TI - Reduced susceptibility to eccentric exercise-induced muscle damage in resistance
trained men is not linked to resistance training-related neural adaptations.
AB - The purpose of this study was to examine the acute effects of maximal concentric
vs. eccentric exercise on the isometric strength of the elbow flexor, as well as
the biceps brachii muscle electromyographic (EMG) responses in resistance-trained
(RT) vs. untrained (UT) men. Thirteen RT men (age: 24 +/- 4 years; height: 180.2
+/- 7.7 cm; body weight: 92.2 +/- 16.9 kg) and twelve UT men (age: 23 +/- 4
years; height: 179.2 +/- 5.0 cm; body weight: 81.5 +/- 8.6 kg) performed six sets
of ten maximal concentric isokinetic (CON) or eccentric isokinetic (ECC) elbow
flexion exercise in two separate visits. Before and after the exercise
interventions, maximal voluntary contractions (MVCs) were performed for testing
isometric strength. In addition, bipolar surface EMG signals were detected from
the biceps brachii muscle during the strength testing. Both CON and ECC caused
isometric strength to decrease, regardless of the training status. However, ECC
caused greater isometric strength decline than CON did for the UT group (p =
0.006), but not for the RT group. Both EMG amplitude and mean frequency
significantly decreased and increased, respectively, regardless of the training
status and exercise intervention. Resistance-trained men are less susceptible to
eccentric exercise-induced muscle damage, but this advantage is not likely linked
to the chronic resistance training-induced neural adaptations.
PMID- 26424923
TI - Aerobic and anaerobic determinants of repeated sprint ability in team sports
athletes.
AB - The aim of this study was to examine in team sports athletes the relationship
between repeated sprint ability (RSA) indices and both aerobic and anaerobic
fitness components. Sixteen team-sport players were included (age, 23.4 +/- 2.3
years; weight, 71.2 +/- 8.3 kg; height, 178 +/- 7 cm; body mass index, 22.4 +/- 2
kg . m(-2); estimated VO2max, 54.16 +/- 3.5 mL . kg(-1) . min(-1)). Subjects were
licensed in various team sports: soccer (n = 8), basketball (n = 5), and handball
(n = 3). They performed 4 tests: the 20 m multi-stage shuttle run test (MSRT),
the 30-s Wingate test (WingT), the Maximal Anaerobic Shuttle Running Test
(MASRT), and the RSA test (10 repetitions of 30 m shuttle sprints (15 + 15 m with
180 degrees change of direction) with 30 s passive recovery in between).
Pearson's product moment of correlation among the different physical tests was
performed. No significant correlations were found between any RSA test indices
and WingT. However, negative correlations were found between MASRT and RSA total
sprint time (TT) and fatigue index (FI) (r = -0.53, p < 0.05 and r = -0.65, p <
0.01, respectively). No significant relationship between VO2max and RSA peak
sprint time (PT) and total sprint time (TT) was found. Nevertheless, VO2max was
significantly correlated with the RSA FI (r = -0.57, p < 0.05). In conclusion,
aerobic fitness is an important factor influencing the ability to resist fatigue
during RSA exercise. Our results highlighted the usefulness of MASRT, in contrast
to WingT, as a specific anaerobic testing procedure to identify the anaerobic
energy system contribution during RSA.
PMID- 26424924
TI - Epidemiology of training injuries in amateur taekwondo athletes: a retrospective
cohort study.
AB - The objectives of this study were to estimate the incidence and describe the
pattern and severity of training injuries in taekwondo, and to compare pattern
and severity of training injuries with competition injuries. One hundred and
fifty-two active Australian amateur taekwondo athletes, aged 12 years or over,
completed an online survey comprising questions on training exposure and injury
history over the preceding 12 months. The main outcome measures were: overall
injury incidence rate per athlete-year; training injury incidence rate per
athlete-year, per 1000 athlete-training-sessions, and per 1000 athlete-hours of
training; injury severity; and injury proportions by anatomical region and by
type of injury. Injury incidence rates were calculated with 95% confidence
intervals using standard methods, while injury proportions were compared using
Fisher's exact test. The vast majority (81.5%) of taekwondo injuries in an
average athlete-year occurred during training. The training injury incidence rate
was estimated to be 1.6 (95% CI: 1.4, 1.9) per athlete-year, 11.8 (95% CI: 10.4,
13.4) per 1000 athlete-training-sessions, and 7.0 (95% CI: 6.1, 7.9) per 1000
athlete-hours of training. Among athletes with five or fewer injuries, the
severity and injury pattern of training injuries were, by and large, the same as
for competition injuries. Approximately sixty percent (60.3%) of training
injuries required treatment by a health professional. Considering the burden of
training injuries exceeds that of competition injuries, taekwondo governing
bodies and stakeholders are encouraged to devote more efforts towards the
identification of risk factors for, and prevention of, training injuries in the
sport of taekwondo.
PMID- 26424925
TI - Long-term effects of graduated compression stockings on cardiorespiratory
performance.
AB - The use of graduated compression stockings (GCS) in sport has been increasing in
the last years due to their potential positive effects for athletes. However,
there is little evidence to support whether these types of garments actually
improve cardiorespiratory performance. The aim of this study was to examine the
cardiorespiratory responses of GCS during running after three weeks of regular
use. Twenty recreational runners performed three tests on different days: test 1)
- a 5-min maximal effort run in order to determine the participants' maximal
aerobic speed; and tests 2) and 3) - a fatigue running test of 30 minutes at 80%
of their maximal aerobic speed with either GCS or PLACEBO stockings at random.
Cardiorespiratory parameters (minute ventilation, heart rate, relative oxygen
consumption, relative carbon dioxide production, ventilatory equivalents for
oxygen and carbon dioxide, and oxygen pulse) were measured. Before each test in
the laboratory, the participants trained with the randomly assigned stockings
(GCS or PLACEBO) for three weeks. No significant differences between GCS and
PLACEBO were found in any of the cardiorespiratory parameters. In conclusion, the
present study provides evidence that running with GCS for three weeks does not
influence cardiorespiratory parameters in recreational runners.
PMID- 26424926
TI - Alternative to traditional stretching methods for flexibility enhancement in well
trained combat athletes: local vibration versus whole-body vibration.
AB - This study aimed to compare the effect of local vibration (LV) and whole body
vibration (WBV) on lower body flexibility and to assess whether vibration
treatments were more effective than traditionally used static and dynamic
stretching methods. Twenty-four well-trained male combat athletes (age: 22.7 +/-
3.3 years) performed four exercise protocols - LV (30 Hz, 4 mm), WBV (30 Hz, 4
mm), static stretching (SS), and dynamic stretching (DS) - in four sessions of
equal duration 48 hours apart in a randomized, balanced order. During a 15-minute
recovery after each protocol, subjects performed the stand and reach test (S&R)
at the 15th second and the 2(nd), 4(th), 6(th), 8(th), 10(th) and 15(th) minute.
There was a similar change pattern in S&R scores across the 15-minute recovery
after each protocol (p = 0.572), remaining significantly elevated throughout the
recovery. A significant main protocol effect was found for absolute change in S&R
scores relative to baseline (p = 0.015). These changes were statistically greater
in LV than WBV and DS. Changes in SS were not significantly different from LV,
but were consistently lower than LV with almost moderate effect sizes. After LV,
a greater percentage of subjects increased flexibility above the minimum
detectable change compared to other protocols. Subjects with high flexibility (n
= 12) benefited more from LV compared with other methods (effect size >= 0.862).
In conclusion, LV was an effective alternative exercise modality to acutely
increase lower extremity flexibility for well-trained athletes compared with WBV
and traditional stretching exercises.
PMID- 26424927
TI - The acute effects of different training loads of whole body vibration on
flexibility and explosive strength of lower limbs in divers.
AB - The purpose of this study was to examine the acute effects of different vibration
loads (frequency and amplitude) of whole-body vibration (WBV) on flexibility and
explosive strength of lower limbs in springboard divers. Eighteen male and female
divers, aged 19 +/- 2 years, volunteered to perform 3 different WBV protocols in
the present study. To assess the vibration effect, flexibility and explosive
strength of lower limbs were measured before (Pre), immediately after (Post 1)
and 15 min after the end of vibration exposure (Post 15). Three protocols with
different frequencies and amplitudes were used in the present study: a) low
vibration frequency and amplitude (30 Hz/2 mm); b) high vibration frequency and
amplitude (50 Hz/4 mm); c) a control protocol (no vibration). WBV protocols were
performed on a Power Plate platform, whereas the no vibration divers performed
the same protocol but with the vibration platform turned off. A two-way ANOVA 3 x
3 (protocol * time) with repeated measures on both factors was used. The level of
significance was set at p < 0.05. Univariate analyses with simple contrasts
across time were selected as post hoc tests. Intraclass coefficients (ICC) were
used to assess the reliability across time. The results indicated that
flexibility and explosive strength of lower limbs were significantly higher in
both WBV protocols compared to the no vibration group (NVG). The greatest
improvement in flexibility and explosive strength, which occurred immediately
after vibration treatment, was maintained 15 min later in both WBV protocols,
whereas NVG revealed a significant decrease 15 min later, in all examined
strength parameters. In conclusion, a bout of WBV significantly increased
flexibility and explosive strength in competitive divers compared with the NVG.
Therefore, it is recommended to incorporate WBV as a method to increase
flexibility and vertical jump height in sports where these parameters play an
important role in the success outcome of these sports.
PMID- 26424928
TI - Effect of whole body vibration frequency on neuromuscular activity in ACL
deficient and healthy males.
AB - Whole-body vibration (WBV) has been shown to enhance muscle activity via reflex
pathways, thus having the potential to contrast muscle weakness in individuals
with rupture of the anterior cruciate ligament (ACL). The present study aimed to
compare the magnitude of neuromuscular activation during WBV over a frequency
spectrum from 20 to 45 Hz between ACL-deficient and healthy individuals. Fifteen
males aged 28+/-4 with ACL rupture and 15 age-matched healthy males were
recruited. Root mean square (RMS) of the surface electromyogram from the vastus
lateralis in both limbs was computed during WBV in a static half-squat position
at 20, 25, 30, 35, 40 and 45 Hz, and normalized to the RMS while maintaining the
half-squat position without vibration. The RMS of the vastus lateralis in the ACL
deficient limb was significantly greater than in the contralateral limb at 25,
30, 35 and 40 Hz (P<0.05) and in both limbs of the healthy participants (dominant
limb at 25, 30, 35, 40 and 45 Hz, P<0.05; non dominant limb at 20, 25, 30, 35, 40
and 45 Hz, P<0.05). The greater neuromuscular activity in the injured limb
compared to the uninjured limb of the ACL-deficient patients and to both limbs of
the healthy participants during WBV might be due to either augmented excitatory
or reduced inhibitory neural inflow to motoneurons of the vastus lateralis
through the reflex pathways activated by vibratory stimuli. The study provides
optimal WBV frequencies which might be used as reference values for ACL-deficient
patients.
PMID- 26424929
TI - Sweat gland density and response during high-intensity exercise in athletes with
spinal cord injuries.
AB - Sweat production is crucial for thermoregulation. However, sweating can be
problematic for individuals with spinal cord injuries (SCI), as they display a
blunting of sudomotor and vasomotor responses below the level of the injury.
Sweat gland density and eccrine gland metabolism in SCI are not well understood.
Consequently, this study examined sweat lactate (S-LA) (reflective of sweat gland
metabolism), active sweat gland density (SGD), and sweat output per gland (S/G)
in 7 SCI athletes and 8 able-bodied (AB) controls matched for arm ergometry
VO2peak. A sweat collection device was positioned on the upper scapular and
medial calf of each subject just prior to the beginning of the trial, with iodine
sweat gland density patches positioned on the upper scapular and medial calf.
Participants were tested on a ramp protocol (7 min per stage, 20 W increase per
stage) in a common exercise environment (21+/-1 degrees C, 45-65% relative
humidity). An independent t-test revealed lower (p<0.05) SGD (upper scapular) for
SCI (22.3 +/-14.8 glands . cm(-2)) vs. AB. (41.0 +/- 8.1 glands . cm(-2)).
However, there was no significant difference for S/G between groups. S-LA was
significantly greater (p<0.05) during the second exercise stage for SCI (11.5+/
10.9 mmol . l(-1)) vs. AB (26.8+/-11.07 mmol . l(-1)). These findings suggest
that SCI athletes had less active sweat glands compared to the AB group, but the
sweat response was similar (SLA, S/G) between AB and SCI athletes. The results
suggest similar interglandular metabolic activity irrespective of overall sweat
rate.
PMID- 26424930
TI - Selected anthropometric variables and aerobic fitness as predictors of
cardiovascular disease risk in children.
AB - The aim of this study was to assess the suitability of body mass index, waist
circumference, waist-to-height ratio and aerobic fitness as predictors of
cardiovascular risk factor clustering in children. A cross-sectional study was
conducted with 290 school boys and girls from 6 to 10 years old, randomly
selected. Blood was collected after a 12-hour fasting period. Blood pressure,
waist circumference (WC), height and weight were evaluated according to
international standards. Aerobic fitness (AF) was assessed by the 20-metre
shuttle-run test. Clustering was considered when three of these factors were
present: high systolic or diastolic blood pressure, high low-density lipoprotein
(LDL) cholesterol, high triglycerides, high plasma glucose, high insulin
concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve
identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio
(WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted
in significant areas under the ROC curves, which was not observed for AF. The
anthropometric variables were good predictors of cardiovascular risk factor
clustering in both sexes, whereas aerobic fitness should not be used to identify
cardiovascular risk factor clustering in these children.
PMID- 26424931
TI - Changes in the acid-base balance and lactate concentration in the blood in
amateur ultramarathon runners during a 100-km run.
AB - The aim of this study was to analyse the acid-base balance and partial pressure
of blood gases of participants during a 100-km run. Fourteen experienced amateur
ultramarathon runners (age: 43.36+/-11.83 years; height: 175.29+/-6.98 cm;
weight: 72.12+/-7.36 kg) completed the 100-km run. Blood samples were taken
before the run; after 25, 50, 75, and 100 km; and 12 and 24 hours after the run.
There were significant differences (p<0.05) between the mean values registered
for acid-alkaline balance, buffering alkalies, and current bicarbonate in each
segment of the run, especially during the third, fourth, and fifth segments of
the run (i.e., between 50 and 100 km), and there were only significant
differences associated with buffering alkalies and current bicarbonate during the
recovery. However, all the changes were within the physiological norm. A
significant decrease in the compressibility of oxygen was observed after 100 km
(from 92.80+/-15.67 to 88.36+/-13.71 mmHg) and continued during the recovery to
75.06+/-8.60 mmHg 12 h after the run. Also there was a decrease in saturation to
a mean value of 93.78+/-3.10 at 12 h after the run. Generally the amateurs
runners are able to adjust their running speed so as not to provoke a significant
acid-base imbalance or lactate acid accumulation.
PMID- 26424932
TI - The effect of uphill stride manipulation on race walking gait.
AB - Stride length analysis represents an easy method for assessing race walking
kinematics. However, the stride parameters emerging from such an analysis have
never been used to design a training protocol aimed at increasing stride length.
With this aim, we investigated the effects of stride frequency manipulation
during three weeks of uphill (2%) training on stride length at iso-efficiency
speed. Twelve male race walkers were randomly allocated to one of two training
groups: stride frequency manipulation (RWM, n=6) and free stride frequency (RWF,
n=6). RESULTS: Kinematic parameters measured before and after the 3-week training
in RWM showed increased stride length (4.54%; p<0.0001) and contact time (4.58%;
p<0.001); inversely, a decreased stride frequency (4.44%; p<0.0001) and internal
work (7.09%; p<0.05) were found. In RWF the effect of the training showed a
decrease in stride length (1.18%; p<0.0001) and contact time (<1%; p<0.0001) with
respect to baseline conditions and an increased stride frequency and internal
work of 1.19% (p<0.0001). These results suggest that using slopes (2%) as RWM
could help coaches to provide some training methods that would improve an
athlete's performance, through increasing stride length without altering his or
her race walking technique or metabolic demands.
PMID- 26424933
TI - On the Question of Effective Sample Size in Network Modeling: An Asymptotic
Inquiry.
AB - The modeling and analysis of networks and network data has seen an explosion of
interest in recent years and represents an exciting direction for potential
growth in statistics. Despite the already substantial amount of work done in this
area to date by researchers from various disciplines, however, there remain many
questions of a decidedly foundational nature - natural analogues of standard
questions already posed and addressed in more classical areas of statistics -
that have yet to even be posed, much less addressed. Here we raise and consider
one such question in connection with network modeling. Specifically, we ask,
"Given an observed network, what is the sample size?" Using simple, illustrative
examples from the class of exponential random graph models, we show that the
answer to this question can very much depend on basic properties of the networks
expected under the model, as the number of vertices nV in the network grows. In
particular, adopting the (asymptotic) scaling of the variance of the maximum
likelihood parameter estimates as a notion of effective sample size, say neff, we
show that whether the networks are sparse or not under our model (i.e., having
relatively few or many edges between vertices, respectively) is sufficient to
yield an order of magnitude difference in neff, from O(nV ) to [Formula: see
text]. We then explore some practical implications of this result, using both
simulation and data on food-sharing from Lamalera, Indonesia.
PMID- 26424934
TI - Hepatitis prevention project in the Korean American community in Killeen, Texas.
AB - Educational efforts related to viral hepatitis have the potential to increase
awareness and identify chronically infected individuals and can lead to
successful vaccination strategies. However, in underserved semirural communities,
such as the Korean American community in Killeen, Texas, these outreach
activities are lacking. The GanYum ("hepatitis" in Korean) Prevention Project
aimed to evaluate thoughts/behaviors, assess vulnerability, and educate Korean
Americans on hepatitis B and C. Two outreach events were held at a Korean church
and a Korean market (O'Mart) to provide education, screening, and outreach about
viral hepatitis. Ninety-six patients were screened at two events. Five patients
were found to be positive for hepatitis B surface antigen and were referred to
their primary care physicians and the liver clinic at Scott & White Healthcare in
Temple, Texas. Fifty-one patients (53%) were found to be immune to hepatitis B,
and 40 patients (42%) were hepatitis B vulnerable. We demonstrated that the
prevalence of chronic hepatitis B in Koreans in our study is similar to the
previously documented prevalence (5%). Our educational efforts were successful in
changing perceptions regarding the modes of transmission and exacerbating factors
of chronic viral hepatitis and encouraged participants to seek care for their
liver diseases, if needed. We found that both venues (the church and Korean
market) were appropriate to screen and educate participants; churches seemed to
have a more engaged audience.
PMID- 26424935
TI - Screening for hepatitis B in patients with lymphoma.
AB - Chronic hepatitis B virus (HBV) infection can be reactivated during lymphoma
chemotherapy, specifically with rituximab. In 2008, the Centers for Disease
Control and Prevention and, in 2010, the American Society of Clinical Oncology
made recommendations that anyone who received cytotoxic or immunosuppressive
therapy should be tested for serologic markers of HBV infection. In our study, we
wanted to determine the screening rates for HBV infection at our institution and
if simply adding a checkbox onto the rituximab order would improve HBV screening.
We performed a retrospective chart review of two cohorts of lymphoma patients at
Scott & White Health Clinic. Cohort 1 included patients from 1993 to 2008. Cohort
2 included patients who received rituximab after an institutionwide protocol
(rituximab order checkbox) was initiated in 2011. A total of 452 patients treated
for lymphoma were reviewed. Only 15 of the 404 Cohort 1 patients received HBV
screening (3.7%; 95% confidence interval, 2.1%-6.1%). Screening rates were
statistically higher if baseline liver laboratory values were elevated (P <
0.0001). HBV was also checked more frequently if patients' liver function tests
became elevated while on chemotherapy, 85.7% (12/14). Of the 48 patients in
Cohort 2, 33 patients (68.7%) received HBV screening. No patients in either
cohort had a positive HBV surface antigen or developed reactivation of HBV during
chemotherapy. The addition of a checkbox on the rituximab order form
significantly increased our screening for HBV infection in lymphoma patients
initiating chemotherapy.
PMID- 26424936
TI - Invited Commentary: Screening for hepatitis B in the immigrant population and
individuals who are in need of immunosuppressive drug therapy.
AB - Chronic hepatitis B (CHB) afflicts approximately 300 million people in the world.
Hepatitis B virus (HBV) is a known carcinogenic virus and continues to be the
leading cause of hepatocellular carcinoma (HCC) (1). Approximately 70% of
hepatitis B surface antigen (HBsAg) carriers reside in intermediate (>2%
prevalence) to high-risk (>8% prevalence) areas such as Asia, the Pacific
Islands, Africa, India, and parts of Southern Europe (1). There is a common
misperception that this disorder is not very common in the United States.
However, 63% of the nearly 28 million immigrants who entered the US between 1974
and 2008 were born in countries of intermediate or high prevalence (2). The
Immigrant Refugee and Migrant Health Branch of the Centers for Disease Control
and Prevention (CDC) estimated that an average of 53,000 CHB cases were imported
to the US yearly from 2004 to 2008. Forty percent of these cases originated from
China, Vietnam, and the Philippines (2). The CDC has recently revised its
prevalence estimates and concluded that 2.2 million US residents are likely to
have chronic HBV infection, of which 1.3 million are judged to be foreign-born
individuals. Even these figures are likely to be too low, however, because the
estimates do not take into account illegal immigrants and other socially
disadvantaged patients. Importantly, HBsAg testing is not required as part of the
process of immigrating into the United States (3). This lack of a requirement for
HBV screening is an important missed opportunity to programmatically diagnose
this condition.
PMID- 26424937
TI - Dual antiplatelet compared to triple antithrombotic therapy in anterior wall
acute myocardial infarction complicated by depressed left ventricular ejection
fraction.
AB - Current guidelines recommend triple antithrombotic therapy (TT) consisting of
warfarin, aspirin, and a P2Y12 inhibitor following an anterior ST elevation
myocardial infarction (STEMI) complicated by extensive wall motion abnormalities.
This recommendation, however, is based on data collected before percutaneous
coronary intervention (PCI) became the standard of care for the treatment of
STEMI. We designed a retrospective study of patients who received PCI for
anterior STEMI over an 8-year period to compare rates of thromboembolic and
bleeding events between patients receiving dual antiplatelet therapy (DAPT) and
those receiving TT, including warfarin. Patients were included if the
predischarge echocardiogram showed extensive wall motion abnormality and an
ejection fraction <=35%. Patients with known left ventricular thrombus were
excluded. A total of 124 patients met the criteria, with 80 patients in the DAPT
group and 44 in the TT group. The median age was 58 years in the TT group and 64
years in the DAPT group (P < 0.04), with an average ejection fraction of 31%.
Thromboembolic events occurred in 4 patients (5%) in the DAPT group compared with
3 patients (6.8%) in the TT group (P = 0.70). Bleeding occurred in 2 patients in
the DAPT group and 4 patients in the TT group (2.5% in DAPT vs. 9.1% in TT group,
P = 0.18). No differences in rates of clinical embolism or left ventricular
thrombus were found. Our data support recent findings that warfarin may not be
indicated for patients following PCI for anterior STEMI, even when significant
wall motion abnormalities and reduced ejection fraction <=35% are present.
PMID- 26424938
TI - Improving compliance with cervical cancer screening guidelines.
AB - Current cervical cancer screening guidelines for the care of healthy women
include HPV cotesting with all Papanicolaou (Pap) smears after the age of 30. To
improve compliance with current guidelines, we instituted two processes: first,
simplifying the ordering process to a single order for Pap smear plus HPV
cotesting using an electronic medical record system (EMR); and second, providing
education for clinic staff. Baseline and postintervention data were collected by
retrospective chart review. Patients were selected during three intervals: prior
to the transition to Epic EMR, after the transition to Epic, and after an
educational intervention. Compliance with standard guidelines was evaluated in
relation to the trial intervals, type of provider, patient age, and duration from
the previous Pap smear. Provider type was analyzed by considering gynecologists
versus nongynecologist providers, and physicians versus mid-level providers.
Overall, the percentage of compliance with HPV test ordering did not differ (P =
0.21) between intervals. Univariate analyses performed to identify factors likely
to be associated with the practice of ordering HPV cotesting only involved the
type of provider. In conclusion, transition to Epic and a training session had
minimal impact on compliance with ordering HPV cotesting at the time of a Pap
smear except among family practice physicians, who did significantly improve
their compliance rate. Gynecologists and mid-level providers were more compliant
with ordering HPV cotesting throughout, but did not significantly improve after
the interventions.
PMID- 26424939
TI - Replacement of the aortic valve with a bioprosthesis at the time of continuous
flow ventricular assist device implantation for preexisting aortic valve
dysfunction.
AB - Left ventricular assist device (LVAD) implantation has become a mainstay of
therapy for advanced heart failure patients who are either ineligible for, or
awaiting, cardiac transplantation. Controversy remains over the optimal
therapeutic strategy for preexisting aortic valvular dysfunction in these
patients at the time of LVAD implant. In patients with moderate to severe aortic
regurgitation, surgical approaches are center specific and range from variable
leaflet closure techniques to concomitant aortic valve replacement (AVR) with a
bioprosthesis. In the present study, we retrospectively analyzed our outcomes in
patients who underwent simultaneous AVR and LVAD implantation secondary to
antecedent aortic valve pathology. Between January 2004 and June 2010, 144
patients underwent LVAD implantation at a single institution. Of these, 7
patients (4.8%) required concomitant AVR. Five of the 7 patients (71%) survived
to hospital discharge and suffered no adverse events in the perioperative period.
One-year survival for the discharged patients was 80%, and no prosthetic valve
related adverse events were observed in long-term follow-up. Given our
experience, we conclude that bioprosthetic AVR is a plausible alternative for end
stage heart failure patients at the time of LVAD implantation.
PMID- 26424940
TI - The gender of authors in the Baylor Proceedings: a reflection of both current
staff composition and lesser number of publications by female physicians.
AB - Gender parity has been achieved in entrance to medical school, but women still
constitute only 32% of the physicians licensed to practice in the state of Texas.
Similarly, female physicians lag behind in scholarly publications. This gender
imbalance appears to be improving, although parity has yet to be achieved in many
journals. We could reliably obtain the gender of both the physician staff of the
North Division of Baylor Scott & White Health and of the authors in Baylor
University Medical Center Proceedings. Of the Baylor authors, 19% were female
physicians, while 65% were male physicians (others were nonphysicians). The
gender makeup of the total staff was 27% female and 73% male physicians. Thus,
female authorship is only 70% as great as the number of female staff physicians.
We suggest ways to encourage more women to submit publications.
PMID- 26424941
TI - Acral vesicles and bullae in a patient with severe rheumatoid arthritis.
AB - We present the case of a 56-year-old black woman with rheumatoid arthritis who
developed worsening fatigue, fever, weight loss, and a vesiculobullous skin
eruption while being treated with certolizumab pegol for her arthritis.
Microscopic findings confirmed the diagnosis of a neutrophilic dermatosis.
PMID- 26424942
TI - Diagnosing and managing peripartum headache.
AB - A 38-year-old gravida 7 para 5 Hispanic woman at 36 weeks and 4 days gestation
presented with a postpartum headache following vaginal delivery complicated by an
unintentional dural puncture for epidural analgesia. Due to the positional nature
of the headache and its frontal and occipital origin, a postdural puncture
headache was diagnosed. After failure of conservative treatment, an epidural
blood patch was used, which offered immediate relief. However, shortly following
the procedure, the parturient's neurological condition deteriorated due to an
unrecognized intraparenchymal and subarachnoid hemorrhage requiring an emergent
craniectomy. This case highlights the importance of diligence when evaluating and
treating postpartum headache despite a classic presentation.
PMID- 26424943
TI - A triad of linezolid toxicity: hypoglycemia, lactic acidosis, and acute
pancreatitis.
AB - We present a case of suspected linezolid toxicity in a 34-year-old man with
sickle cell disease and line-related vancomycin-resistant enterococcal bacteremia
and tricuspid valve endocarditis. The patient developed sudden-onset
hypoglycemia, lactic acidosis, and acute pancreatitis 11 days after initiation of
linezolid. All adverse effects quickly resolved with drug cessation. The
pathophysiology underlying this triad of linezolid toxicity is unclear, but may
be related to mitochondrial dysfunction.
PMID- 26424944
TI - Microscopic polyangiitis causing diffuse alveolar hemorrhage and rapidly
progressive glomerulonephritis.
AB - Diffuse alveolar hemorrhage complicating small vessel vasculitis is a life
threatening emergency and should be considered in the differential diagnosis of
patients who develop rapidly progressive dyspnea with alveolar opacities on chest
imaging. In these patients, the coexistence of pulmonary and renal involvement
suggests a multisystem disease. We present a case of a man who presented to our
hospital with diffuse alveolar hemorrhage, severe anemia, and rapidly progressive
glomerulonephritis.
PMID- 26424945
TI - Noncirrhotic hyperammonemia causing relapsing altered mental status.
AB - Hyperammonemia is a recognized cause of encephalopathy. However, it is commonly
seen in patients with liver disease. The clinical entity of noncirrhotic
hyperammonemia is now being increasingly recognized. We report a man who
presented to our hospital with relapsing altered mental status later diagnosed as
noncirrhotic hyperammonemia.
PMID- 26424946
TI - Synthetic cannabinoids and acute kidney injury.
AB - Synthetic cannabinoids (SCB) are a family of chemicals that bind to cannabinoid
receptors and cause psychoactive effects. Over the past few years, they have been
increasingly used for recreational purposes, especially by young adults, and have
been reported to have many adverse effects. Acute kidney injury (AKI) has been
recently reported; the pathophysiology of SCB-induced AKI is unknown. We report
three cases of AKI in the setting of SCB use. The peak serum creatinine levels
ranged from 3.0 to 5.7 mg/dL; one patient required hemodialysis. SCB can induce
AKI.
PMID- 26424947
TI - Gastropericardial fistula as a delayed complication of a Nissen fundoplication.
AB - A 41-year-old man presented to the emergency department with substernal chest
pain and was found to have ST elevations in the inferior leads on his
electrocardiogram. An emergent cardiac catheterization did not identify
significant coronary narrowing. Computed tomography of the thorax demonstrated a
pneumopericardium and a hiatal hernia. The patient had a complicated past
surgical history, including a Nissen fundoplication and three additional
surgeries for postoperative complications. An esophagram later revealed an ulcer
and possible fistula, and the patient underwent gastropericardial fistula
resection after the fistula failed to close with fibrin sealant application.
Enteropericardial fistulas occur infrequently but have high morbidity and
mortality rates. This possibility is much more likely in patients with prior
gastroesophageal surgery, including laparoscopic Nissen fundoplication.
PMID- 26424948
TI - Fatal pulmonary tumor thrombotic microangiopathy caused by undiagnosed metastatic
gastric adenocarcinoma.
AB - Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare cause of rapidly
progressive dyspnea in a background of metastatic cancer. Gastric adenocarcinoma
is the neoplasm most frequently associated with PTTM. Unfortunately, PTTM is
difficult to identify clinically and is most commonly a postmortem diagnosis. We
present the case of a woman with no previous diagnosis of cancer who presented
with rapidly progressive shortness of breath. She was diagnosed with severe
pulmonary arterial hypertension and rapidly succumbed to her illness. A
postmortem diagnosis of PTTM was established based on autopsy results.
PMID- 26424949
TI - Transjugular intrahepatic portosystemic shunt creation using a three-dimensional
fluoroscopy guidance system in patients with the Budd-Chiari syndrome.
AB - When performed for Budd-Chiari syndrome (BCS), transjugular intrahepatic
portosystemic shunt (TIPS) creation can be technically difficult due to hepatic
congestion and asymmetric hypertrophy. We present three female patients with
decompensated BCS in whom TIPS were created using a three-dimensional fluoroscopy
guidance system. On a dedicated workstation using three-dimensional volumes of
computed tomography imaging, a virtual needle path was created by the operator
extending from the needle entry point (hepatic vein stump or inferior vena cava)
to the target portal vein. Subsequently, the virtual needle path was overlaid on
the fluoroscopy image for guidance of portal venous cannulation. This technology
can be used for TIPS procedures in patients with BCS and other complex TIPS
cases, as it may help delimit the trajectory of the needle pass and optimally
result in more efficient procedures with decreased radiation dose.
PMID- 26424950
TI - Late presentation of adenovirus-induced hemorrhagic cystitis and ureteral
obstruction in a kidney-pancreas transplant recipient.
AB - We report a late presentation of adenovirus-induced renal allograft and bladder
infection causing azotemia and hemorrhagic cystitis in a patient 5 years after
simultaneous kidney-pancreas transplantation. Adenovirus has been increasingly
recognized as a cause of morbidity and mortality in both solid organ and stem
cell transplant recipients. We wish to emphasize the importance of early
detection, as treatment options involve reduction of immunosuppression, followed
by the addition of antiviral agents and supportive care.
PMID- 26424952
TI - Iron deficiency and hemolytic anemia reversed by ventricular septal myectomy.
AB - Hemolytic anemia has been reported to occur in the setting of aortic stenosis and
prosthetic heart valves, but much more rarely in association with obstructive
hypertrophic cardiomyopathy (HC). Of the few descriptions of hemolytic anemia
secondary to HC, all but one case involved bacterial endocarditis contributing to
left ventricular outflow tract obstruction. We present the case of a 67-year-old
man with recurrent hemolytic anemia and HC, without infective endocarditis.
Attempts at iron repletion and augmentation of beta-blocker therapy proved his
anemia to be refractory to medical management. Ventricular septal myectomy led to
the resolution of hemolysis, anemia, and its coexisting symptoms.
PMID- 26424951
TI - Heart transplantation in the Ehlers-Danlos syndrome.
AB - We describe a woman with Ehlers-Danlos syndrome and aortic aneurysm who
experienced a myocardial infarction due to spontaneous left circumflex coronary
artery dissection 3 weeks postpartum. She developed end-stage heart failure and
subsequently underwent a successful orthotopic heart transplantation. To our
knowledge, this is the first report of a heart transplant performed in an
individual with Ehlers-Danlos syndrome.
PMID- 26424953
TI - Unruptured sinus of Valsalva aneurysm presenting with concurrent Morgagni hernia.
AB - We describe a patient with dyspnea and intermittent cyanosis who was found to
have concurrent right diaphragmatic and right atrial masses, initially thought to
have advanced vascular sarcoma. She was ultimately diagnosed with an unruptured
sinus of Valsalva aneurysm, a Morgagni hernia, and a patent foramen ovale. Her
dyspnea and cyanosis resolved after sequential surgical correction of these
defects.
PMID- 26424954
TI - Surgical repair of renal artery aneurysms.
AB - The pathogenesis of renal artery aneurysms (RAAs) is degenerative, which
eventually leads to weakening of the vessel wall and, in extreme cases, rupture.
RAAs are a rare occurrence. Patients generally are asymptomatic, with a small
number presenting with uncontrollable hypertension or hematuria. Most RAAs are
discovered incidentally on imaging and do not pose an immediate health threat.
However, the risk of rupture is an indication for prophylactic repair in certain
patients. Interest in interventional radiologic procedures in the management of
RAAs has recently increased; however, open repair should still be considered in
select instances. In this case series, we present three patients for whom an open
approach was indicated and performed.
PMID- 26424955
TI - Effectiveness of balloon valvuloplasty for stenosis of a bioprosthesis in the
tricuspid valve position.
AB - A 67-year-old man underwent percutaneous balloon valvuloplasty for bioprosthetic
tricuspid stenosis. He had undergone two tricuspid valve replacements over a
period of 39 years and became symptomatic. After the valvuloplasty, his symptoms
were resolved. Stenosis of a bioprosthetic tricuspid valve can be successfully
and safely treated with balloon valvuloplasty.
PMID- 26424956
TI - Multivessel transradial percutaneous coronary angioplasty in a single coronary
artery originating from the right sinus of Valsalva.
AB - Percutaneous coronary intervention in patients with an anomalous coronary artery
is technically challenging. Selective cannulation and coaxial positioning in the
anomalous artery and optimum stability during the procedure are pivotal for
successful completion of the procedure. Selection of the appropriate guide
catheter is of paramount importance in these situations. In patients with
congenital coronary artery anomalies, increasing use of multidetector computed
tomography for cardiac imaging may yield diagnostic information not obtained with
coronary angiography. Axial, multiplanar, and three-dimensional volume-rendered
reconstructions aid in detecting and interpreting such anomalies and in selecting
appropriate hardware during percutaneous coronary intervention in these patients.
We report a case of successful stent implantation in the right coronary artery
and proximal circumflex coronary artery in a patient with a single coronary
artery arising from the right sinus of Valsalva.
PMID- 26424957
TI - Two-time recurrence of a right atrial myxoma.
AB - We report a case of a second recurrence of a right atrial myxoma in a 38-year-old
woman who had surgical excision in March 2008 and excision of a recurrence in
August 2012. She presented with a similar clinical picture in December 2014 and
again underwent surgical excision. The case is unusual both for its location in
the right atrium and its multiple recurrences in a sporadic form without any sign
of the myxoma complex.
PMID- 26424958
TI - Myxedema coma with cardiac tamponade and severe cardiomyopathy.
AB - Myxedema coma is an infrequent but potentially fatal complication of
hypothyroidism. We present a rare case of previously undiagnosed hypothyroidism
presenting in cardiogenic shock from pericardial tamponade and depressed
myocardial contractility in myxedema coma. Here, we focus on cardiovascular
complications associated with the condition.
PMID- 26424959
TI - Myocardial infarction with ventricular septal rupture and cardiogenic shock.
PMID- 26424960
TI - Morphologic demonstration of spontaneous and surgical closure of membranous
ventricular septal defect.
AB - This report demonstrates morphologic features of membranous ventricular septal
defect that was closed spontaneously in one patient and operatively in the other.
PMID- 26424962
TI - What my cancer taught me.
PMID- 26424961
TI - A review of spontaneous closure of ventricular septal defect.
AB - Ventricular septal defect (VSD) is the most common congenital heart malformation
and can be detected during the prenatal and postnatal period, in childhood, and
in adulthood. Spontaneous closure of VSD can be determined through a variety of
methods-echocardiography, Doppler color flow imaging, angiography, auscultation,
and cardiac catheterization-and can be proven by pathological evidence at
necropsy. There are two major types of VSD, membranous and muscular, as well as
the perimembranous variety, which comprises variable portions of the adjacent
muscular septum but lacks the membranous septum. VSD appears either as an
isolated cardiac defect without other abnormalities or with several complex
malformations. It has long been recognized that VSD can close spontaneously, but
the incidence of spontaneous VSD closure is still uncertain. Since necropsy study
of the hearts with VSD has rarely been reported, information on morphological
features of spontaneous VSD closure remains limited. In addition, the mechanisms
for spontaneous VSD closure are not fully understood. Herein, we present a brief
review of the incidence of spontaneous VSD closure, morphological characteristics
of the closure, and the main mechanisms responsible for the closure.
PMID- 26424963
TI - Reflections on Sir Roger Bannister and his autobiography, Twin Tracks.
PMID- 26424964
TI - Feroze Novroji Ghadially, 1920-2014: a personal remembrance.
PMID- 26424965
TI - A week in Havana, Cuba, in February 2015.
PMID- 26424966
TI - Facts and ideas from anywhere.
PMID- 26424968
TI - Proinflammatory Cytokines Increase Vascular Endothelial Growth Factor Expression
in Alveolar Epithelial Cells.
AB - Vascular endothelial growth factor (VEGF) is an endothelial permeability mediator
that is highly expressed in lung epithelium. In nonlung cells proinflammatory
cytokines have been shown to increase VEGF expression, but their effects on lung
epithelium remain unclear. We hypothesized that increases in alveolar epithelial
cell VEGF RNA and protein expression occur after exposure to proinflammatory
cytokines. We tested this using human alveolar epithelial cells (A549) stimulated
with 5 proinflammatory cytokines. VEGF RNA expression was increased 1.4-2.7-fold
in response to IL-1, IL-6, IL-8, TNF-alpha, or TGF-beta over 6 hours, with TGF
beta having the largest response. TNF-alpha increased VEGF RNA as early as 1
hour. A mix of IL-1, IL-6, and IL-8 had effects similar to IL-1. TNF-alpha
increased protein expression as early as 4 hours and had a sustained effect at 16
hours, whereas IL-1 did not increase protein expression. Only VEGF165 was present
in cultured A549 cells, yet other isoforms were seen in human lung tissue.
Increased expression of VEGF in alveolar epithelial cells occurs in response to
proinflammatory cytokines. Increased VEGF expression likely contributes to the
pathogenesis of inflammatory lung diseases and to the angiogenic phenotype of
lung cancer, a disease typically preceded by chronic inflammation.
PMID- 26424970
TI - Protecting our specialty.
PMID- 26424971
TI - Dr. Fernando Ortiz-Monasterio.
PMID- 26424967
TI - Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases:
A Novel Contributor to Inflammation?
AB - The coordination of tissue function is mediated by gap junctions (GJs) that
enable direct cell-cell transfer of metabolic and electric signals. GJs are
formed by connexin (Cx) proteins of which Cx43 is most widespread in the human
body. Beyond its role in direct intercellular communication, Cx43 also forms
nonjunctional hemichannels (HCs) in the plasma membrane that mediate the release
of paracrine signaling molecules in the extracellular environment. Both HC and GJ
channel function are regulated by protein-protein interactions and
posttranslational modifications that predominantly take place in the C-terminal
domain of Cx43. Matrix metalloproteases (MMPs) are a major group of zinc
dependent proteases, known to regulate not only extracellular matrix remodeling,
but also processing of intracellular proteins. Together with Cx43 channels, both
GJs and HCs, MMPs contribute to acute inflammation and a small number of studies
reports on an MMP-Cx43 link. Here, we build further on these reports and present
a novel hypothesis that describes proteolytic cleavage of the Cx43 C-terminal
domain by MMPs and explores possibilities of how such cleavage events may affect
Cx43 channel function. Finally, we set out how aberrant channel function
resulting from cleavage can contribute to the acute inflammatory response during
tissue injury.
PMID- 26424972
TI - Vascularised composite allotransplants: Transplant of upper extremities and face.
AB - Transplantation of solid organs and bone marrow has become a highly acceptable
and often the only available clinical solution in many situations. It has been
practiced across the globe for quite a long time since the first kidney
transplant in 1954. Transplantation of tissues other than these, which was termed
composite tissue allotransplantation and currently as vascularised composite
allotransplantation (VCA) is gaining acceptance as a solution for complex
reconstructive problems. This involves the transfer of multiple types of tissue
such as bone, muscle, nerve, skin and blood vessels. The advantage of these over
the conventional reconstructive methods is its ability to give aesthetically and
functionally superior equal composite substitute to the missing or deformed part.
The composite tissues transplanted commonly include the upper extremities, face
and abdominal wall. Among these, hand transplants were the first to be done and
have been carried out more than any other VCA. This article reviews the current
scenario of VCA especially of the hand and face, in the light of experience of
the two bilateral hand transplants done recently in India.
PMID- 26424973
TI - Namaste (counterbalancing) technique: Overcoming warping in costal cartilage.
AB - BACKGROUND: Indian noses are broader and lack projection as compared to other
populations, hence very often need augmentation, that too by large volume. Costal
cartilage remains the material of choice in large volume augmentations and repair
of complex primary and secondary nasal deformities. One major disadvantage of
costal cartilage grafts (CCG) which offsets all other advantages is the tendency
to warp and become distorted over a period of time. We propose a simple technique
to overcome this menace of warping. MATERIALS AND METHODS: We present the data of
51 patients of rhinoplasty done using CCG with counterbalancing technique over a
period of 4 years. RESULTS: No evidence of warping was found in any patient up to
a maximum follow-up period of 4 years. CONCLUSION: Counterbalancing is a useful
technique to overcome the problem of warping. It gives liberty to utilize even
unbalanced cartilage safely to provide desired shape and use the cartilage
without any wastage.
PMID- 26424974
TI - Magnetic resonance neurography of the brachial plexus.
AB - Magnetic Resonance Imaging (MRI) is being increasingly recognised all over the
world as the imaging modality of choice for brachial plexus and peripheral nerve
lesions. Recent refinements in MRI protocols have helped in imaging nerve tissue
with greater clarity thereby helping in the identification, localisation and
classification of nerve lesions with greater confidence than was possible till
now. This article on Magnetic Resonance Neurography (MRN) is based on the
authors' experience of imaging the brachial plexus and peripheral nerves using
these protocols over the last several years.
PMID- 26424975
TI - Magnetic resonance neurography of the brachial plexus.
PMID- 26424969
TI - Trachoma and Ocular Chlamydial Infection in the Era of Genomics.
AB - Trachoma is a blinding disease usually caused by infection with Chlamydia
trachomatis (Ct) serovars A, B, and C in the upper tarsal conjunctiva.
Individuals in endemic regions are repeatedly infected with Ct throughout
childhood. A proportion of individuals experience prolonged or severe
inflammatory episodes that are known to be significant risk factors for ocular
scarring in later life. Continued scarring often leads to trichiasis and in
turning of the eyelashes, which causes pain and can eventually cause blindness.
The mechanisms driving the chronic immunopathology in the conjunctiva, which
largely progresses in the absence of detectable Ct infection in adults, are
likely to be multifactorial. Socioeconomic status, education, and behavior have
been identified as contributing to the risk of scarring and inflammation. We
focus on the contribution of host and pathogen genetic variation, bacterial
ecology of the conjunctiva, and host epigenetic imprinting including small RNA
regulation by both host and pathogen in the development of ocular pathology. Each
of these factors or processes contributes to pathogenic outcomes in other
inflammatory diseases and we outline their potential role in trachoma.
PMID- 26424976
TI - How were lipofilling cannulae designed and are they as safe as we believe?
AB - BACKGROUND: Most practitioners in plastic surgery believe that blunt tipped
cannulae are safer. Interestingly, there is no study about their safety, and the
problem is exactly this. As the use of blunt tipped cannulae is somehow
difficult, some surgeons try other extreme alternatives, such as sharp and
cutting tipped injection needles. But, they can cause complications such as
vessel damage. According to these hypotheses, we tried to design a cannula which
would ease the application of lipofilling and which would minimise the trauma.
Contrary to the injection needle, the tips of the cannula would be blunter, and
trauma would be diminished. OBJECTIVES: After designing such a cannula, we
compared it with the most frequently used Coleman type cannulae with regard to
ease in utilisation, and safety. We also tried to evaluate the potential for
trauma, of the regularly used cannulae. MATERIALS AND METHODS: In the first part,
the penetration capacity of all cannulae was measured and compared, and in the
second part, the tissue damage was evaluated in an experimental model. RESULTS:
According to the statistical and histological findings, the pointed-tip cannulae,
blunted to a certain degree, can be applied easily through the tissues. The
surgeon works more comfortably and we have noted that these cannulae cause less
tissue damage.
PMID- 26424977
TI - Objective analysis of microtia reconstruction in Indian patients and
modifications in management protocol.
AB - INTRODUCTION: An ideal ear, with representation of all anatomic landmarks, is the
aim of any reconstructive surgeon embarking on reconstructing the ear in a
microtia patient. The literature is abundant with the description of techniques,
but these have been reported mainly in Caucasian and Oriental population. There
have been very few publications on results in the population belonging to the
Indian subcontinent. In spite of strictly adhering to the recommended techniques
of reconstruction, the results obtained in these patients have often been marred
by problems that are not reported with the Oriental or Caucasian populations.
This may necessitate a relook into the management strategy of these cases.
Hindering the assessment of the results, their reporting and auditing the
improvement obtained by such change in the management strategy, is the lack of a
standardized method for assessment of the outcome. Hence, an attempt was made in
a series of patients who underwent microtia reconstruction to assess the outcome
using a new tool based on the attained definition of anatomical components of the
reconstructed pinna. Further effort was made to document the modifications in the
technical execution of the reconstruction during the period of the study.
MATERIALS AND METHODS: A retrospective review of 44 patients and a prospective
analysis of 11 patients, who underwent ear reconstruction for microtia from
December 2003 to September 2014 at a tertiary care teaching hospital, was
undertaken. Taking a cue from Nagata's description of an 'ideal reconstructed
ear' which should show all the anatomical components, we developed an objective
grading system to assess our results. The technique had undergone several changes
during these years combining the principles of three universally accepted
methods, that is, those described by Nagata, Brent, and Firmin. These changes, as
well as the reasons behind them, were documented. RESULTS: On objectively
measuring and analysing the replication of normal morphologic characteristics of
the reconstructed ears, we documented progressive improvement of our results.
Good or excellent results could be achieved in 70% of cases in the second group
compared to a poor outcome in more than 2/3(rd) of the cases carried out during
the initial period. Based on these results and the changes adopted in our
practice we propose suggestions for management of microtia cases in the Indian
population. CONCLUSIONS: An objective, weighted grading system has further
enabled us to critically evaluate the outcomes and to further improve upon the
existing results. Our amalgamation of the salient features of the established
techniques as well as changes made based on our experience has enabled us to get
good results more consistently in our attempts at microtia reconstruction. We
believe that the adoption of such amalgamated methods will be more suitable in
Indian patients.
PMID- 26424978
TI - Thoracodorsal artery perforator flap: Indeed a versatile flap.
AB - INTRODUCTION: The thoracodorsal artery perforator (TDAP) flap has emerged as one
of the ideal perforator flaps. We, hereby, describe its versatility in
indications (free/pedicled), methods of harvest (patient position and paddle
orientation) and perforator consistency. MATERIALS AND METHODS: We have performed
a total of six TDAP flaps-five free and one pedicled, over a period of 1-year
from March 2014 to February 2015 at a single centre. Our indications have been:
Reconstruction of oral cavity, breast and upper and lower extremities. RESULTS:
We had neither any failures nor any re-explorations. The average perforator
length is about 6 cm and the pedicle length can be extended to 12-14 cm by
including the thoracodorsal artery. There is inconsistency in perforator
position; however, the presence of a perforator is certain. It can be harvested
in lateral, prone or supine position, thus, does not require any position change
allowing a two-team approach to reconstruction. The paddle can be oriented
vertically or horizontally, both healing with scars in inconspicuous locations.
Apart from providing a good colour match for extremities, this flap can be
thinned primarily. CONCLUSION: The versatility of TDAP has several advantages
that make it a workhorse flap for most reconstructions requiring soft tissue
cover. Further, the ease of harvest makes it a good perforator flap for
beginners. Its use in chimerism with the underlying latissimus dorsi muscle
provides reconstruction for coverage and volume replacement.
PMID- 26424979
TI - Single nucleotide polymorphism of bone morphogenetic protein 4 gene: A risk
factor of non-syndromic cleft lip with or without palate.
AB - BACKGROUND: The bone morphogenetic protein (BMP) signalling pathway is crucial in
a number of developmental processes and is critical in the formation of variety
of craniofacial elements including cranial neural crest, facial primordium,
tooth, lip and palate. It is an important mediator in regulation of lip and
palate fusion, cartilage and bone formation. AIM: To study the role of mutation
of BMP4 genes in the aetiology of non-syndromic cleft lip with or without palate
(NSCL +/- P) and identify it directly from human analyses. MATERIALS AND METHODS:
A case-control study was done to evaluate whether BMP4T538C polymorphism,
resulting in an amino acid change of Val=Ala (V152A) in the polypeptide, is
associated with NSCL +/- P in an Indian paediatric population. Genotypes of 100
patients with NSCL +/- P and 100 controls (in whom absence of CL +/- P was
confirmed in three generations) were detected using a polymerase chain reaction
restriction fragment length polymorphism strategy. Logistic regression was
performed to evaluate allele and genotype association with NSCLP. RESULTS:
Results showed significant association between homozygous CC genotype with CL +/-
P (odds ratio [OR]-5.59 and 95% confidence interval [CI] = 2.85-10.99). The 538C
allele carriers showed an increased risk of NSCL +/- P as compared with 538 T
allele (OR - 4.2% CI = 2.75-6.41). CONCLUSION: This study suggests an association
between SNP of BMP4 gene among carriers of the C allele and increased risk for
NSCLP in an Indian Population. Further studies on this aspect can scale large
heights in preventive strategies for NSCLP that may soon become a reality.
PMID- 26424980
TI - Single nucleotide polymorphism of BMP4 Gene: A risk factor of non-syndromic cleft
lip with or without cleft palate.
PMID- 26424981
TI - Arterial segments as microvascular interposition grafts in venous anastomosis in
digital replantations.
AB - INTRODUCTION: Microvascular anastomosis is a crucial procedure in replantation
surgeries. Venous insufficiency is one of the most consistent cause of failure or
re-exploration in these surgeries necessitating the use of venous grafts.
MATERIALS AND METHODS: We discuss our study of 9 such replantation surgeries
executed in calendar year 2013-2014, including a double finger replantation done
in the same patient having total amputation of 4 fingers of the same (right)
hand, in which an arterial segment was used as a microvascular interposition
graft for venous anastomosis. Out of these 9 surgeries, 3 were re-exploration
procedures for venous compromise and 6 were successful primary replantations.
RESULTS: In all, 8 replants were successful and one failed due to arterial
compromise. DISCUSSION: In our experience and extensive review of the previously
available literature, we would like to portray the advantages of arterial
segments as microvascular grafts in replant surgeries. Specifically, in a crush
amputation injury for which the use of a vascular interposition graft is being
contemplated. If any other digit is also amputated and is unsuitable for
replantation, it can act as a potential donor site to harvest the arterial
segment. However, when dealing with single finger amputation, the surgeon must be
confident about the single digital arterial anastomosis, before harvesting the
second digital artery as a microvascular graft. CONCLUSION: In our study, we
found the use of arterial grafts in microvascular anastomosis of veins
advantageous, as arterial segments have better ability to resist spasm due to
environmental changes, better pressure tolerance as compared to venous segments,
and provide an appropriate calibre match and ease of harvest in the same
operative field.
PMID- 26424982
TI - "Ride-on" technique and other simple and logical solutions to counter most common
complications of silicone implants in augmentation rhinoplasty.
AB - Augmentation rhinoplasty can be carried out using a wide range of materials
including autologous bone and/or cartilage as well as alloplasts. Use of biologic
bone and cartilage grafts results in lower infection rates, but they are
associated with long-term resorption and donor-site morbidity. Alloplastic
materials, in particular silicone, have been associated in literature with
extrusion, necrosis of the tip, mobility and deviation or displacement of the
implant, immobile nasal tip and infection. However, they have the advantages of
being readily available and easy to reshape with no requirement for harvesting
autografts. AIM: To overcome these problems associated with silicone implants for
which the authors have devised a novel technique, the "rideon technique".
MATERIALS AND METHODS: The present study was carried out on 11 patients over a
period of 4 years. The authors have devised a simple technique to fix the
silicone implant and retain it in place. Restricting the implant to only dorsum
avoided common complications related to the silicone implant. RESULTS: The
authors have used this technique in 11 patients with encouraging results. Follow
up ranged from 12 months to 36 months during which patients were assessed for
implant mobility, implant extrusion and tip necrosis. There was no incidence of
above mentioned complications in these patients. CONCLUSION: The "rideon
technique" provides excellent stability to silicone implants and restricting the
implant only to dorsum not only eliminates chances of tip necrosis and thus
implant extrusion but also maintains natural shape, feel and mobility of the tip.
PMID- 26424983
TI - White Roll Vermilion turn down flap in primary unilateral cleft lip repair: A
novel approach.
AB - AIM: Numerous modifications of Millard's technique of rotation - advancement
repair have been described in literature. This article envisions a new
modification in Millard's technique of primary unilateral chieloplasty. MATERIAL
AND METHODS: Eliminating or reducing the secondary deformities in children with
cleft lip has been a motivating factor for the continual refinement of cleft lip
surgical techniques through the years. Vermilion notching, visibility of
paramedian scars and scar contracture along the white roll are quite noticeable
in close-up view even in good repairs. Any scar is less noticeable if it is in
midline or along the lines of embryological closure. White Roll Vermilion turn
down Flap (WRV Flap), a modification in the Millard's repair is an attempt to
prevent these secondary deformities during the primary cleft lip sugery. This
entails the use of white roll and the vermilion from the lateral lip segment for
augmenting the medial lip vermilion with the final scar in midline at the
vermilion. RESULT: With an experience of more than 100 cases of primary cleft lip
repair with this technique, we have achieved a good symmetry and peaking of
cupid's bow with no vermilion notching of the lips. CONCLUSION: WRV flap aims to
high light the importance of achieving a near normal look of the cleft patient
with the only drawback of associated learning curve with this technique.
PMID- 26424984
TI - White roll vermilion-turn down flap in primary unilateral cleft lip repair: A
novel approach.
PMID- 26424985
TI - Tunica vaginalis flap following 'Tubularised Incised Plate' urethroplasty to
prevent urethrocutaneous fistulaa.
AB - INTRODUCTION: Surgery for hypospadias has been continuously evolving, implying
thereby that no single technique is perfect and suitable for all types of
hypospadias. Snodgrass technique is presently the most common surgical procedure
performed for hypospadias. MATERIALS AND METHODS: We analysed the results of
tunica vaginalis flap (TVF) as an additional cover to the tubularised incised
plate (TIP) repair. RESULTS: A total of 35 patients of hypospadias were repaired
using TIP urethroplasty and TVF as a second layer. Mean age at the time of
presentation was 6.63 +/- 3.4 years. Post-operative complications namely wound
infection, flap necrosis, scrotal haematoma, scrotal abscess, urethral fistula,
meatal stenosis were recorded and analysed during follow-up period. Need for re
do surgery was considered as failure of the operative procedure. Out of 35
patients, 8 (22.85%) patients had proximal penile hypospadias and 27 (77.14%)
patients had distal penile hypospadias. Mean post-operative follow-up was 24.53
months. During the follow-up complications noticed included wound infection (n =
2), urethrocutaneous fistula (n = 1) and meatal stenosis (n = 1). Wound infection
was managed with appropriate antibiotics as per hospital policy/culture and
sensitivity reports. Meatal stenosis responded to bougie dilatation/calibration
during follow-up. CONCLUSION: To conclude, TVF as an additional cover is
associated with an acceptable complication rate and good cosmetic results if
performed with meticulous tissue handling.
PMID- 26424986
TI - Surgical revirgination: Four vaginal mucosal flaps for reconstruction of a hymen.
AB - INTRODUCTION: Over centuries, virginity has been given social, religious and
moral importance. It is widely believed as a state of a female who has never
engaged in sexual intercourse, and her hymen is intact. Hymenoplasty for torn
hymen is carried out not only for the sake of cultural and religious traditions
but also for the social status and interpersonal relationships. MATERIALS AND
METHODS: 2.5 cm long and 1 cm wide four vaginal mucosal flaps were raised from
the anterior vaginal wall just behind labia minora. Two flaps were based
proximally, and their two opposing flaps were based distally. These flaps were
overlapped in a crisscross fashion and were sutured with 5/0 Polyglactin
(Vicryl((r))) sutures leaving no area raw. The donor area was closed primarily.
When some remains of a torn hymen were found, one to three vaginal mucosal flaps
were added to its remains as per the need for reconstruction. RESULTS: We
operated upon 11 patients. In nine cases, the hymen was reconstructed with four
flaps. In remaining two, it was reconstructed from the remains using vaginal
mucosal flaps. All flaps healed without any infection or disruption. Sutures got
absorbed in 25-35 days. In all cases, this newly constructed barrier broke with
only moderate pressure at the time of penetrative sex serving the purpose of the
surgery completely. CONCLUSION: Erasing evidence of the sexual history simply by
'Surgical Revirgination' is extremely important to women contemplating marriage
in cultures where a high value is placed on virginity.
PMID- 26424987
TI - Extended effect after a single dose of type A botulinum toxin for asymmetric
masseter muscle hypertrophy.
AB - Facial asymmetry can either be physiological or pathological and is a common
cosmetic concern. A 35-year-old Indian male presented with broad appearing lower
face and prominent left jaw since adolescence. Parotid enlargement and other
local disorders were ruled out. Ultrasonographic thickness of right masseter
muscle was 13 mm while that of left was 14.9 mm, in unclenched state. Type-A
botulinum toxin (T-ABT) was injected, evenly at five points, in both muscles
within the "safe zone". Using a 29 gauge needle, 15 and 25 international units
were delivered to right and left masseters, respectively. Six months post -
injection, a reduction of 2.9 mm and 4.4 mm was observed along with a reduced
external facial asymmetry. At 24 months, patient maintains a satisfactory facial
contour with no significant early or late post-injection complications. Intra
massteric injection of T-ABT can be used effectively as a primary or adjunct
procedure for holistic oculo-facial sculpting.
PMID- 26424988
TI - Bony tumour in an unusual location on the mandible.
AB - Osteomas are benign osteogenic tumors that are seen in the facial bones, but
uncommonly in the mandible. In the facial bones, both central and peripheral
osteomas have been described. Peripheral osteomas have been described to occur in
the frontal, ethmoid, and maxillary sinuses but are not common in jawbones. When
in the mandible, they are usually found over the angle and inferior border of the
mandible. We report on a solitary peripheral osteoma located unusually in the
sigmoid notch of the left mandible causing facial asymmetry.
PMID- 26424989
TI - Congenital urethrocutaneous fistula in an adolescent male.
AB - A urethrocutaneous fistula is a common complication after hypospadias repair, but
congenital fistula is a rare anomaly. We present a 16-year-old boy with this
unusual anomaly. Its etiology, embryology, and management are discussed in brief.
PMID- 26424990
TI - A rare case of plexiform schwannoma of the lower lip: Treatment and management.
AB - An 18-year-old female presented with a swelling on the lower lip, which was
insidious in onset and gradually progressive. The mass was completely excised
under local anaesthesia. Complete histopathologic and immunohistochemical studies
were conducted. The Antoni A areas were found along with typical verocay bodies
composed of palisading nuclei and surrounding spaces filled with eosinophilic
filaments. No necrosis was noted and there were no atypical mitotic figures. In
the Antoni B region, a closely textured matrix with areas of edema, myxomatous
changes, cystic degeneration and dilated vessels were noted. On the basis of the
histopathologic and immunohistochemical staining with S-100 protein, a diagnosis
of plexiform schwannoma was made and has been reported in this study. The post
operative view confirmed complete recovery after 6 weeks of surgery. This is a
rare case with the tumour located in the lower lip, as very few cases have been
reported in literature and it may be the first one reported from India.
PMID- 26424991
TI - Intraosseous keratin cyst of the distal phalanx.
AB - Keratin or epidermoid cysts of the phalanges are rare lesions mimicking
osteolytic lesions such as infection, malignancy and other tumours. Definitive
diagnosis can be made by histopathology only and treatment is by simple excision
and curettage. We present a case of intraosseous keratin cyst of the distal
phalanx and review of literature.
PMID- 26424992
TI - A word of caution.
PMID- 26424993
TI - Hyperbaric oxygen and topical oxygen are different treatments.
PMID- 26424994
TI - Innovation and beyond: Dangers in improvised negative pressure wound therapy
systems.
PMID- 26424995
TI - The levels of evidence of articles published by Indian authors in Indian journal
of plastic surgery.
PMID- 26424996
TI - Giant lipoma of the back.
PMID- 26424997
TI - Extended uses of scalp vein set in plastic surgery.
PMID- 26424998
TI - Universal Splint for upper limb support during reconstruction by pedicled
abdominal flap.
PMID- 26424999
TI - Temporal artery rupture following firework rocket injury.
PMID- 26425000
TI - Mayo clinic.
PMID- 26425002
TI - Controversies in contraception for women with epilepsy.
AB - Contraception is an important choice that offers autonomy to women with regard to
prevention of unintended pregnancies. There is wide variation in the
contraceptive practices between continents, countries, and societies. The medical
eligibility for contraception for sexually active women with epilepsy (WWE) is
determined by the type of anti-epileptic drugs (AEDs) that they use. Enzyme
inducing AEDs such as phenobarbitone, phenytoin, carbamazepine, and oxcarbazepine
increase the metabolism of orally administered estrogen (and progesterone to a
lesser extent). Estrogen can increase the metabolism of certain AEDs, such as
lamotrigine, leading to cyclical variation in its blood level with resultant
adverse effect profile or seizure dyscontrol. AEDs and sex hormones can increase
the risk of osteoporosis and fracture in WWE. The potential interactions between
AEDs and hormonal contraception need to be discussed with all women in
reproductive age-group. The alternate options of oral contraception such as
intrauterine copper device, intrauterine levonorgestrel release system, and
supplementary protection with barriers need to be presented to them. World Health
Organization has recommended to avoid combination contraceptive pills containing
estrogen and progesteron in women who desire contraception and in breastfeeding
mothers. Care providers need to consider the option of non-enzyme-inducing AEDs
while initiating long-term treatment in adolescent and young WWE.
PMID- 26425001
TI - Epilepsy in India I: Epidemiology and public health.
AB - Of the 70 million persons with epilepsy (PWE) worldwide, nearly 12 million PWE
are expected to reside in India; which contributes to nearly one-sixth of the
global burden. This paper (first of the two part series) provides an in-depth
understanding of the epidemiological aspects of epilepsy in India for developing
effective public health prevention and control programs. The overall prevalence
(3.0-11.9 per 1,000 population) and incidence (0.2-0.6 per 1,000 population per
year) data from recent studies in India on general population are comparable to
the rates of high-income countries (HICs) despite marked variations in population
characteristics and study methodologies. There is a differential distribution of
epilepsy among various sociodemographic and economic groups with higher rates
reported for the male gender, rural population, and low socioeconomic status. A
changing pattern in the age-specific occurrence of epilepsy with preponderance
towards the older age group is noticed due to sociodemographic and
epidemiological transition. Neuroinfections, neurocysticercosis (NCC), and
neurotrauma along with birth injuries have emerged as major risk factors for
secondary epilepsy. Despite its varied etiology (unknown and known), majority of
the epilepsy are manageable in nature. This paper emphasizes the need for focused
and targeted programs based on a life-course perspective and calls for a stronger
public health approach based on equity for prevention, control, and management of
epilepsy in India.
PMID- 26425004
TI - Single small enhancing CT Lesions, with special reference to neurocysticercosis:
How I treat.
AB - Single small enhancing CT lesions (SSECTL) have been very commonly encountered in
clinical practice. These lesions typically are small (often < 20 mm), enhancing
as a ring lesion or a disc and with varying amounts of surrounding edema. Most
SSECTL present as focal seizures. Once the diagnosis of SSECTL and likely to be a
solitary cysticercus lesion is made, the patient is given appropriate AED
therapy. Depending on the resolution pattern on repeat imaging performed at
intervals not less than six months if patient remains asymptomatic, cysticidal
therapy is instituted along with AEDs. Any deviation from the classical clinical
or radiological patterns needs further evaluation and other etiologies described
for the SSECTL will need to be ruled out, including that of tuberculosis. Largely
these lesions resolve and the clinical condition remains benign and in most
patients AEDs can be withdrawn in two to three years period.
PMID- 26425003
TI - Ipsipulsion: A forgotten sign of lateral medullary syndrome.
AB - Ipsipulsion is a clinical sign specifically seen in lateral medullary syndrome.
It is characterized by two involuntary phenomenons. One is static eye deviation
ipsilateral to the side of lesion especially in the absence of visual fixation.
Second is the saccadic lateropulsion whereby voluntary saccades towards the side
of lesion are hypermetric and saccades towards opposite side are hypometric. The
vertical saccades may also appear oblique. Ipsipulsion is produced due to damage
to the contralateral olivocerebellar pathways that crosses midline in medulla and
pass through the ipsilateral inferior cerebellar peduncle to supply ipsilateral
cerebellar hemisphere.
PMID- 26425005
TI - Joseph Godwin Greenfield: The father of neuropathology (1884-1958).
AB - The systematic study of neuropathology was initiated by Godwin Greenfield in the
early part of the 20(th) century. He worked at the National Hospital, Queen
Square, London for the major period of his life and worked on various subjects
like cerebrospinal fluid, intracranial tumours, cerebellar ataxias, dystrophia
myotonica, disseminated sclerosis, subacute combined degeneration of the spinal
cord, and the like. After his retirement he visited the National Institute of
Neurological Diseases and Blindness in Bethesda, Maryland, USA, from time to time
and there he died suddenly from myocardial infarction.
PMID- 26425006
TI - Pure neuritic leprosy: Resolving diagnostic issues in acid fast bacilli (AFB)
negative nerve biopsies: A single centre experience from South India.
AB - BACKGROUND AND PURPOSE: Demonstration of lepra bacilli is essential for definite
or unequivocal diagnosis of pure neuritic leprosy (PNL) on nerve biopsy. However,
nerves always do not show bacilli owing to the changes of previous therapy or due
to low bacillary load in tuberculoid forms. In absence of granuloma or lepra
bacilli, other morphologic changes in endoneurium and perineurium can be of help
in making a probable diagnosis of PNL and treating the patient with multidrug
therapy. MATERIALS AND METHODS: Forty-six biopsies of PNL were retrospectively
reviewed and histologic findings were compared with 25 biopsies of non leprosy
neuropathies (NLN) including vasculitic neuropathy and chronic inflammatory
demyelinating polyneuropathy (CIDP). The distribution of endoneurial infiltrate
and fibrosis, perineurial thickening, and myelin abnormalities were compared
between PNL and NLN biopsies and analyzed by Chi-square test. RESULTS: Out of 46
PNL casses, 24 (52.17 %) biopsies were negative for acid fast bacilli (AFB). In
these cases, the features which favor a diagnosis of AFB-negative PNL were
endoneurial infiltrate (51.1%), endoneurial fibrosis (54.2%), perineurial
thickening (70.8%), and reduced number of myelinated nerve fibers (75%).
INTERPRETATION AND CONCLUSION: Nerve biopsy is an efficient tool to diagnose PNL
and differentiate it from other causes of NLN. In absence of AFB, the diagnosis
of PNL is challenging. In this article, we have satisfactorily evaluated the
various hisopthological features and found that endoneurial inflammation, dense
fibrosis, and reduction in the number of myelinated nerve fibers are strong
supportive indicators of PNL regardless of AFB positivity.
PMID- 26425007
TI - Sleep changes during prophylactic treatment of migraine.
AB - AIMS: To assess sleep quality in patients with primary headaches before and after
prophylactic treatment using a validated sleep-screening instrument. MATERIALS
AND METHODS: A total of 147 patients, including 63 tension type headache (TTH)
and 84 migraine patients were included. Patients were examined in terms of
frequency and severity of headaches and sleep quality before and 12 weeks after
prophylactic treatment with either propranolol or amitriptyline. RESULTS:
Baseline Visual Analogue Score (VAS) in migraine patients was 7.99 +/- 1.39
compared with 6.86 +/- 1.50 in TTH group (P < 0.001). VAS score after the first
month of treatment was 6.08 +/- 1.88 in migraine patients and 5.40 +/- 1.61 in
TTH (P = 0.023). VAS scores decreased after the third month of treatment to 4.32
+/- 2.29 in migraine patients and 4.11 +/- 1.66 in TTH patients (P = 0.344). The
decrease was significant for patients treated with amitriptyline but not for
those with propranolol. Baseline Pittsburgh Sleep Quality (PSQI) scores were 5.93
+/- 2.43 in migraine patients and 6.71 +/- 2.39 in TTH patients. Poor quality of
sleep (PSQI >= 6) prior to prophylactic treatment was observed in 61.4% of
migraine patients and in 77.7% of TTH patients. Comparison of PSQI scores before
and 3 months following treatment showed significantly improved quality of sleep
in all treatment groups; the greatest significance was detected in migraine
patients with initial PSQI scores of >=6 and treated with amitriptyline (P <
0.001). CONCLUSIONS: Increased understanding of routine objective sleep measures
in migraine patients is needed to clarify the nature of sleep disturbances
associated with primary headaches. This may in turn lead to improvements in
headache treatments.
PMID- 26425008
TI - Hindi translation and validation of Cambridge-Hopkins Diagnostic Questionnaire
for RLS (CHRLSq).
AB - BACKGROUND: Restless legs syndrome also known as Willis-Ekbom's Disease (RLS/WED)
is a common illness. Cambridge-Hopkins diagnostic questionnaire for RLS (CHRLSq)
is a good diagnostic tool and can be used in the epidemiological studies.
However, its Hindi version is not available. Thus, this study was conducted to
translate and validate it in the Hindi speaking population. MATERIALS AND
METHODS: After obtaining the permission from the author of the CHRLSq, it was
translated into Hindi language by two independent translators. After a series of
forward and back translations, the finalized Hindi version was administered to
two groups by one of the authors, who were blinded to the clinical diagnosis.
First group consisted of RLS/WED patients, where diagnosis was made upon face to
face interview and the other group - the control group included subjects with
somatic symptoms disorders or exertional myalgia or chronic insomnia. Each group
had 30 subjects. Diagnosis made on CHRLSq was compared with the clinical
diagnosis. STATISTICAL ANALYSIS: Analysis was done using Statistical Package for
Social Sciences (SPSS) v 21.0. Descriptive statistics was calculated. Proportions
were compared using chi-square test; whereas, categorical variables were compared
using independent sample t-test. Sensitivity, specificity, and positive
predictive value of the translated version of questionnaire were calculated.
RESULTS: Average age was comparable between the cases and control group (RLS/WED
= 39.1 +/- 10.1 years vs 36.2 +/- 11.4 years in controls; P = 0.29). Women
outnumbered men in the RLS/WED group (87% in RLS/WED group vs 57% among controls;
chi(2) = 6.64; P = 0.01). Both the sensitivity and specificity of the translated
version was 83.3%. It had the positive predictive value of 86.6%. CONCLUSION:
Hindi version of CHRLSq has positive predictive value of 87% and it can be used
to diagnose RLS in Hindi speaking population.
PMID- 26425009
TI - Serial macro-architectural alterations with levodopa in Parkinson's disease:
Polysomnography (PSG)-based analysis.
AB - PURPOSE: We studied the sleep macroarchitecture with polysomnography (PSG) in
drug naive patients with Parkinson's disease (PD) and reassessed them following
treatment with levodopa. MATERIALS AND METHODS: This prospective hospital-based
study included 15 patients with PD (age: 59 +/- 11.2 years, duration of PD: 11.8
+/- 12.3 months; and male: female (M:F) = 11:4). They were assessed for
demography, phenotype, modified Hoehn and Yahr staging (H & Y); Schwab and
England and Activities of Daily Living (S and E ADL) Scale; and Unified PDRating
Scale (UPDRS). Sleep was assessed using Epworth Sleepiness Scale (ESS),
Pittsburgh Sleep Quality Index (PSQI), and National Institute of Mental Health
and Neurosciences (NIMHANS) comprehensive sleep disorder questionnaire. They
underwent overnight PSG at baseline and after13.3 +/- 5.7 months of levodopa (440
mg/day). RESULTS: Patients with PD had responded to levodopa as indicated by the
significant improvement in UPDRS motor score in ON state compared to OFF state.
Nocturnal sleep quality indices did not vary significantly, but the excessive
daytime somnolence improved (P = 0.04) with levodopa. Sleep efficiency (P =
0.65), latency to sleep onset (P = 0.19), latency to stage 1 (P = 0.12), and
duration of stage 1 (P = 0.55) had increased. Duration of 'awake in bed' (P =
0.24), slow wave sleep (P = 0.29), and rapid eye movement (REM) sleep (P = 0.24)
decreased with treatment. Periodic leg movements (PLMs) had reduced (P = 0.68)
and mean oxygen saturation during sleep improved (P = 0.002). Surprisingly, snore
index (P < 0.03) during sleep had increased with levodopa. CONCLUSIONS: Sleep
alterations in PD occur even in early stages due to the disease process. There
was improvement in most of the parameters of sleep macroarchitecture with
levodopa.
PMID- 26425010
TI - Vitamin D as a marker of cognitive decline in elderly Indian population.
AB - OBJECTIVES: Very few studies in India have addressed the role of vitamin D in
cognitive function. The present study was conducted to assess the serum levels of
25-hydroxyvitamin D (25(OH)D) and its association with markers of cognitive
impairment and homocysteine levels in the elderly Indian population. MATERIALS
AND METHODS: The study population consisted of patients with dementia (Group A, n
= 32), mild cognitive impairment (MCI; Group B, n = 24), and elderly age-matched
controls (Group C, n = 30). Measurement of serum levels of 25(OH)D and total
homocysteine were done. RESULTS: Significant decreased concentration of 25(OH)D
and increased concentration of homocysteine was observed. Association of serum
levels of vitamin D with markers of cognitive decline as well as serum
homocysteine levels was observed in patients with dementia and MCI when compared
to controls. CONCLUSION: Correlation of vitamin D with markers of cognitive
decline and homocysteine opens a new door for early diagnosis of cognitive
impairment.
PMID- 26425011
TI - Effect of apolipoprotein E (APO E) polymorphism on leptin in Alzheimer's disease.
AB - BACKGROUND: Leptin, a 16 kDa peptide hormone synthesized and secreted
specifically from white adipose cells protects neurons against amyloid beta
induced toxicity, by increasing Apolipoprotein E (APO E)-dependent uptake of beta
amyloid into the cells, thereby, protect individuals from developing Alzheimer's
disease (AD). The APO E epsilon4 allele is a known genetic risk factor for AD by
accelerating onset. It is estimated that the lifetime risk of developing AD
increases to 29% for carriers with one epsilon4 allele and 9% for those with no
epsilon4 allele. OBJECTIVES: To determine the levels of serum leptin,
cholesterol, low density lipoprotein (LDL-C), and high density lipoprotein (HDL
C) in the diagnosed cases of AD and the association of them with cognitive
decline and Apolipoprotein E (APO E) genotypes in AD. MATERIALS AND METHODS:
Serum levels of serum leptin, cholesterol, LDL-C, and HDL-C along with APO E
polymorphism were studied in 39 subjects with probable AD and 42 cognitive normal
individuals. RESULTS: AD group showed significantly lower levels of leptin (P =
0.00) as compared to control group. However, there was no significant difference
in cholesterol, triglycerides, LDL-C, and HDL-C levels in AD and control groups.
The frequency of epsilon4 allele in AD (38.5%) was found to be significantly
higher than in control (10.3%). epsilon3 allele was more frequent than epsilon4
allele in AD and control group.
PMID- 26425012
TI - Treatment of pediatric chronic inflammatory demyelinating polyneuropathy:
Challenges, controversies and questions.
AB - Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon
acquired disorder of unknown cause, presumed to have an immunological basis. We
report 20 patients seen at Children's Hospital Los Angeles over a period of 10
years. The outcome of our patients was favorable in a vast majority with good
response to various treatments instituted. However, residual neurologic deficit
was common. The choice of treatment modality was empirical and selected by the
treating neurologist. Intravenous immunoglobulin (IVIG) and corticosteroids were
most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil,
rituximab, cyclophosphamide, azathioprine, and abatacept were added if the
patients were refractory to IVIG or became corticosteroid dependent. The spectrum
of disease severity ranged from a single monophasic episode, to multiphasic with
infrequent relapses with good response to IVIG, to progressive disease refractory
to multiple therapies.
PMID- 26425014
TI - "Nine" syndrome: A new neuro-ophthalmologic syndrome: Report of two cases.
AB - "Eight-and-a-half" syndrome is a rare condition involving the ipsilateral
abducens nucleus or paramedian pontine reticular formation (PPRF), the
ipsilateral medial longitudinal fasciculus (MLF), and the adjacent facial
colliculus/facial nerve fascicle. The condition is often caused by a lesion
(vascular or demyelinating) in the dorsal tegmentum of the caudal pons. There are
new variants of this syndrome caused by extension of lesion to involve new
adjacent structures in pontine tegmentum. We report two patients with different
etiology presenting with clinical features suggestive of eight-and-a-half
syndrome associated with hemiataxia representing "nine" syndrome (81/2 + 1/2 = 9)
adding new dimension to "eight-and-a-half" syndrome.
PMID- 26425013
TI - Statin-induced bilateral foot drop in a case of hypothyroidism.
AB - Muscle involvement is a common manifestation of both clinical and subclinical
hypothyroidism, with serum creatine kinase (CK) elevation being probably the most
common manifestation, and is seen in up to 90% of patients, but is usually mild
(less than 10 times the upper limit of normal). Rhabdomyolysis is a distinctively
uncommon presentation of hypothyroidism described usually in the setting of
precipitating events such as strenuous exercise, alcohol, or statin use. Rarely
rhabdomyolysis and myoedema seen in hypothyroidism can be complicated by the
development of anterior compartment syndrome leading to neurovascular
compression. We describe a case of a patient with hypothyroidism who developed
acute onset bilateral foot drop on initiation of statins. This case highlights
the need for cautious use of statins in patients at risk for rhabdomyolysis.
PMID- 26425015
TI - A case of Erdheim Chester disease with central nervous system involvement.
AB - Erdheim Chester disease (ECD) is a rare non-Langerhans cell histiocytosis,
commonly involving the musculoskeletal system. Other tissue can also be involved,
including the central nervous system with wide spectrum of clinical features, at
times being nonspecific. This can cause diagnostic dilemmas with delay in
diagnosis and initiation of therapy. Here we describe a 63-year-old man who had
presented with ataxia and behavioral changes, bony pains, weight loss, and
fatigue. His computed tomography (CT), 99Tc scintigraphy and histopathological
features on bone biopsy were consistent with ECD. Thus, ECD should be considered
as a differential diagnosis in patients presenting with bony pain and nonspecific
features of multiorgan involvement.
PMID- 26425016
TI - Diffusion MRI features of acute encephalopathy due to stopping steroid medication
abruptly in congenital adrenal hyperplasia.
AB - Congenital adrenal hyperplasia (CAH) is characterized by adrenal steroid
biosynthesis defect. Steroid replacement therapy should be performed regularly in
these patients. Adrenal crisis may be present in acute stress due to increased
cortisol requirements or in steroid deficiency due to stopping steroid medication
abruptly. In patients with acute adrenal insufficiency, severe hypotension or
hypovolemic shock occurs typically. Acute encephalopathy can be seen due to
hypoxia, hypervolemia, or hypoglycemia. Diffusion restriction can be seen in
cortical-subcortical regions of frontal and parieto-occipital lobes and in
splenium of corpus callosum. In CAH patients with neurologic symptoms, Diffusion
weighted images (DWI) is very important in the diagnosis and follow-up of acute
encephalopathy.
PMID- 26425017
TI - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive
to steroids (CLIPPERS): A case report and review of literature.
AB - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive
to steroids (CLIPPERS) is a recently described inflammatory disease of central
nervous system with distinct clinical and radiological features. The
etiopathogenesis of this rare entity remains to be understood. The
histopathological findings closely resemble chronic inflammatory diseases like
sarcoidosis and malignancies like lymphoma. With advancements in serology,
immunopathology and radiology CLIPPERS is identified as a distinct entity that
differs considerably in its clinical presentation, immunopathology, radiological
findings and response to steroids. We describe a case that presented to us with
progressive quadriparesis and lower cranial nerve deficits whose radiological and
pathological findings were consistent with CLIPPERS. The patient had a good
outcome with long term immunosuppression.
PMID- 26425018
TI - An uncommon initial presentation of snake bite-subarachnoid hemorrhage: A case
report with literature review.
AB - Snake bites are very common in India, particularly in West Bengal. Snake bite can
cause various hematological, neuromyopathical complications. It can be very fatal
if not detected and treated early. Timely intervention can save the patient. We
are reporting a case of hematotoxic Russell viper snake bite presented with
subarachnoid hemorrhage. Patient was successfully treated with antivenom serum
(AVS) along with other conservative management. Subarachnoid hemorrhage as an
initial presentation in viper bite is very rare and we discuss the case with
proper literature review.
PMID- 26425019
TI - An unusual case of bloody tears.
AB - Conjunctival bleeding although occurs in many pathological conditions enlisting
diseases like purulent conjunctivitis, infection with epstian bar virus, and
accidental damage to conjunctiva. We report here a rare case of bloody tears
which was accompanied with severe headache in a12-years school-going girl.
PMID- 26425020
TI - Moyamoya disease; suspecting on conventional MRI brain without angiography.
PMID- 26425021
TI - A unique presentation of atypical SREDA pattern in a young healthy woman.
AB - Subclinical rhythmic electrographic discharge of adults (SREDA) is an EEG pattern
seen in normal individuals and others with different diseases. we report a case
of healthy young woman with alleged epilepsy but normal responsiveness during
sustained SREDA. SREDA is a rare EEG variant with variable clinical significance.
This is the first report of atypical SREDA in a 25 year-old woman.
PMID- 26425022
TI - Montelukast-associated Churg-Strauss syndrome with mononeuritis multiplex.
PMID- 26425023
TI - Bilateral symmetrical parieto occipital involvement in dengue infection.
PMID- 26425024
TI - Antiphospholipid syndrome is an important modifiable risk factor of stroke in the
young.
PMID- 26425025
TI - Conducting case control study on a cross-sectional database.
PMID- 26425026
TI - "Comments on intravenous thrombolysis in acute ischemic stroke in a known case of
left atrial myxoma".
PMID- 26425027
TI - Intravenous thrombolysis in a patient with left atrial myxoma with acute ischemic
stroke.
PMID- 26425028
TI - Sleep quality and health complaints among nursing students.
PMID- 26425029
TI - Electroconvulsive therapy for refractory status epilepticus in a child: A case
report.
PMID- 26425030
TI - Erratum: Impulse control disorders and related behaviours (ICD-RBs) in
Parkinson's disease patients: Assessment using "Questionnaire for impulsive
compulsive disorders in Parkinson's disease" (QUIP): Erratum.
AB - [This corrects the article on p. 49 in vol. 18, PMID: 25745311.].
PMID- 26425031
TI - Vogt-Koyanagi-Harada syndrome presenting with encephalopathy: Retraction.
AB - [This retracts the article on p. 128 in vol. 17, PMID: 24753681.].
PMID- 26425032
TI - Histone Deacetylases and Their Regulatory MicroRNAs in Hepatocarcinogenesis.
AB - A growing body of evidence suggests that epigenetic modifications are promising
potential mechanisms in cancer research. Among the molecules that mediate
epigenetic mechanisms, histone deacetylases (HDACs) are critical regulators of
gene expression that promote formation of heterochromatin by deacetylating
histone and non-histone proteins. Aberrant regulation of HDACs contributes to
malignant transformation and progression in a wide variety of human cancers,
including hepatocellular carcinoma (HCC), gastric cancer, lung cancer, and other
cancers. Thus, the roles of HDACs have been extensively studied because of their
potential as therapeutic targets. However, the underlying mechanism leading to
deregulation of individual HDACs remains largely unknown. Some reports have
suggested that functional microRNAs (miRNAs) modulate epigenetic effector
molecules including HDACs. Here, we describe the oncogenic or tumor suppressive
functions of HDAC families and their regulatory miRNAs governing HDAC expression
in hepatocarcinogenesis.
PMID- 26425033
TI - Essential Components of Educational Programs on Biomedical Writing, Editing, and
Publishing.
AB - The primary objective of educational programs on biomedical writing, editing, and
publishing is to nurture ethical skills among local and international researchers
and editors from diverse professional backgrounds. The mechanics, essential
components, and target outcomes of these programs are described in this article.
The mechanics covers the objectives, design, benefits, duration, participants and
qualifications, program formats, administrative issues, and mentorship. The
essential components consist of three core schedules: Schedule I Basic aspects of
biomedical writing, editing, and communications; Schedule II Essential skills in
biomedical writing, editing, and publishing; and Schedule III Interactive
lectures on relevant topics. The target outcomes of the programs comprise
knowledge acquisition, skills development, paper write-up, and journal
publication. These programs add to the prestige and academic standing of the host
institutions.
PMID- 26425034
TI - HIF-1alpha Upregulation due to Depletion of the Free Ubiquitin Pool.
AB - Hypoxia-inducible factor 1alpha (HIF-1alpha), which transactivates a variety of
hypoxia-induced genes, is rapidly degraded under nomoxia through the
hydroxylation-ubiquitination-proteasome pathway. In this study, we addressed how
HIF-1alpha is stabilized by proteasome inhibitors. The ubiquitin pool was rapidly
reduced after proteasome inhibition, followed by the accumulation of non
ubiquitinated HIF-1alpha. The poly-ubiquitination of HIF-1alpha was resumed by
restoration of free ubiquitin, which suggests that the HIF-1alpha stabilization
under proteasome inhibition is attributed to depletion of the free ubiquitin
pool. Ni(2+) and Zn(2+) also stabilized HIF-1alpha with depletion of the free
ubiquitin pool and these effects of metal ions were attenuated by restoration of
free ubiquitin. Ni(2+) and Zn(2+) may disturb the recycling of free ubiquitin, as
MG132 does. Based on these results, the state of the ubiquitin pool seems to be
another critical factor determining the cellular level of HIF-1alpha.
PMID- 26425035
TI - Presumed Regional Incidence Rate of Out-of-Hospital Cardiac Arrest in Korea.
AB - The regional incidence rates of out-of-hospital cardiac arrest (OHCA) were
traditionally calculated with the residential population as the denominator. The
aim of this study was to estimate the true incidence rate of OHCA and to
investigate characteristics of regions with overestimated and underestimated OHCA
incidence rates. We used the national OHCA database from 2006 to 2010. The
nighttime residential and daytime transient populations were investigated from
the 2010 Census. The daytime population was calculated by adding the daytime
influx of population to, and subtracting the daytime outflow from, the nighttime
residential population. Conventional age-standardized incidence rates (CASRs) and
daytime corrected age-standardized incidence rates (DASRs) for OHCA per 100,000
person-years were calculated in each county. A total of 97,291 OHCAs were
eligible. The age-standardized incidence rates of OHCAs per 100,000 person-years
were 34.6 (95% CI: 34.3-35.0) in the daytime and 24.8 (95% CI: 24.5-25.1) in the
nighttime among males, and 14.9 (95% CI: 14.7-15.1) in the daytime, and 10.4 (95%
CI: 10.2-10.6) in the nighttime among females. The difference between the CASR
and DASR ranged from 35.4 to -11.6 in males and from 6.1 to -1.0 in females.
Through the Bland-Altman plot analysis, we found the difference between the CASR
and DASR increased as the average CASR and DASR increased as well as with the
larger daytime transient population. The conventional incidence rate was
overestimated in counties with many OHCA cases and in metropolitan cities with
large daytime population influx and nighttime outflow, while it was
underestimated in residential counties around metropolitan cities.
PMID- 26425036
TI - Therapeutic Effects of Mesenchymal Stem Cells for Patients with Chronic Liver
Diseases: Systematic Review and Meta-analysis.
AB - Based on their ability to differentiate into multiple cell types including
hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been
suggested as an effective therapy for chronic liver diseases. The aim of this
study was to evaluate the safety, efficacy and therapeutic effects of MSCs in
patients with chronic liver disease through a literature-based examination. We
performed a systematic review (SR) and meta-analysis (MA) of the literature using
the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to
identify clinical studies in which patients with liver diseases were treated with
MSC therapy. Of the 568 studies identified by the initial literature search, we
analyzed 14 studies and 448 patients based on our selection criteria. None of the
studies reported the occurrence of statistically significant adverse events, side
effects or complications. The majority of the analyzed studies showed
improvements in liver function, ascites and encephalopathy. In particular, an MA
showed that MSC therapy improved the total bilirubin level, the serum albumin
level and the Model for End-stage Liver Disease (MELD) score after MSC treatment.
Based on these results, MSC transplantation is considered to be safe for the
treatment of chronic liver disease. However, although MSCs are potential
therapeutic agents that may improve liver function, in order to obtain meaningful
insights into their clinical efficacy, further robust clinical studies must be
conducted to evaluate the clinical outcomes, such as histological improvement,
increased survival and reduced liver-related complications, in patients with
chronic liver disease.
PMID- 26425037
TI - Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients
with Acute Myeloid Leukemia Ineligible for Transplantation.
AB - For decades, maintenance chemotherapy has failed to improve the cure rate or
prolong the survival of patients with acute myeloid leukemia (AML), other than
those with acute promyelocytic leukemia. Immediately after the first complete
remission following consolidation therapy was obtained, oral maintenance
chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and
continued for two years in transplant-ineligible AML patients. Leukemia-free
survival (LFS) and overall survival (OS) were studied and compared between these
patients and the historical control group who did not receive maintenance
therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among
these patients, 27 received oral maintenance chemotherapy. No significant
difference was found in the patients' characteristics between the maintenance and
the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30)
months in the maintenance and the control groups, respectively (P = 0.202). In
the multivariate analysis, the presence of maintenance therapy was an independent
prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit
from maintenance chemotherapy was remarkable in older patients (>= 60 yr) (P =
0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those
with initial low blast count in peripheral blood (P = 0.044), and those receiving
less than two cycles of consolidation therapy (P = 0.017). Maintenance oral
chemotherapy as a post-remission therapy can prolong the survival of patients
with AML who are not eligible for transplantation, particularly older patients,
those with intermediate or unfavorable cytogenetics, those with initial low blast
count, and those receiving less than two cycles of consolidation therapy.
PMID- 26425038
TI - TERT Polymorphism rs2853669 Influences on Lung Cancer Risk in the Korean
Population.
AB - Short telomeres are known as one of the risk factors for human cancers. The
present study was conducted to evaluate the association between 6 polymorphisms,
which were related with short telomere length in the Korean population, and lung
cancer risk using 1,100 cases and 1,096 controls. Among the 6 polymorphisms, TERT
rs2853669 was significantly associated with increased lung cancer risk under a
recessive model (odds ratio [OR]=1.38, 95% confidence interval [CI]=1.05-1.81,
P=0.02). The effect of rs2853669 on lung cancer risk was significant in younger
individuals (OR=1.73, 95% CI=1.18-2.54, P=0.005) and adenocarcinoma (OR=1.50, 95%
CI=1.07-2.07, P=0.02). Our results suggest that a common functional promoter
polymorphism, TERT rs2853669, may influence both telomere length and lung cancer
risk in the Korean population.
PMID- 26425040
TI - Clinico-pathological Analysis of the Lungs from Patients with Lung
Transplantation in a Single Institute in Korea.
AB - Recently, the numbers of lung transplantation (LT) has been increased in Korea.
However, post-LT outcome has not been successful in all patients, which may be
partially affected by the primary lung disease. Therefore comprehensive
understanding in original pathological diagnosis of patients with LT would be
needed for achieving better clinical outcome. To address this issue, we performed
clinico-pathological analysis of the explanted lungs from 29 patients who
underwent LT over a 9-yr period in Seoul National University Hospital. Among
them, 26 patients received single (1/26) or double (25/26) LT, while heart-lung
transplantation was performed in 3 patients. The final clinico-pathological
diagnoses were idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP)
(n = 6), acute interstitial pneumonia (AIP)/diffuse alveolar damage (DAD) (n =
4), AIP/non-specific interstitial pneumonia with DAD (n = 1), collagen vascular
disease-related interstitial lung disease (CVD-ILD)/DAD (n = 3), CVD-ILD/UIP (n =
1), lymphangioleiomyomatosis (n = 1), bronchiectasis (n = 4), pulmonary arterial
hypertension (n = 2), tuberculosis (n = 1), bronchiolitis obliterans (BO) (n =
1), and lung cancer (n = 1). Moreover, 4 patients who had chemotherapy and
hematopoietic stem cell transplantation due to hematologic malignancy showed
unclassifiable interstitial pneumonia with extensive fibrosis in the lungs. Our
study demonstrates that pathology of the explanted lungs from Korean patients
with LT is different from that of other countries except for interstitial lung
disease and bronchiectasis, which may be helpful for optimization of selecting LT
candidates for Korean patients.
PMID- 26425039
TI - Baseline Characteristics of the Korean Registry of Pulmonary Arterial
Hypertension.
AB - Despite recent advances in understanding of the pathobiology and targeted
treatments of pulmonary arterial hypertension (PAH), epidemiologic data from
large populations have been limited to western countries. The aim of the Korean
Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the
epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a
nationwide, multicenter, prospective data collection using an internet webserver
from September 2008 to December 2011. A total of 625 patients were enrolled. The
patients' mean age was 47.6 +/- 15.7 yr, and 503 (80.5%) were women. The
diagnostic methods included right heart catheterization (n = 249, 39.8%) and
Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency,
were connective tissue disease (CTD), congenital heart disease, and idiopathic
PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional
class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received
a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%)
patients received combination therapy. Incident cases during the registry
represented 297 patients; therefore, the incidence rate of PAH was 1.9
patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates
were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients
exhibited similar age, gender, and survival rate compared with western
registries, they showed relatively more CTD-PAH in the etiology and also systemic
lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and
more specialized therapies should be needed to improve the survival of PAH
patients.
PMID- 26425041
TI - Role of Atypical Pathogens and the Antibiotic Prescription Pattern in Acute
Bronchitis: A Multicenter Study in Korea.
AB - The role of atypical bacteria and the effect of antibiotic treatments in acute
bronchitis are still not clear. This study was conducted at 22 hospitals (17
primary care clinics and 5 university hospitals) in Korea. Outpatients (aged >=
18 yr) who had an acute illness with a new cough and sputum (<= 30 days) were
enrolled in 2013. Multiplex real-time polymerase chain reaction (RT-PCR) was used
to detect five atypical bacteria. A total of 435 patients were diagnosed as
having acute bronchitis (vs. probable pneumonia, n = 75), and 1.8% (n = 8) were
positive for atypical pathogens (Bordetella pertussis, n = 3; B. parapertussis, n
= 0; Mycoplasma pneumoniae, n = 1; Chlamydophila pneumoniae, n = 3; Legionella
pneumophila, n = 1). Among clinical symptoms and signs, only post-tussive
vomiting was more frequent in patients with atypical pathogens than those without
(P = 0.024). In all, 72.2% of the enrolled patients received antibiotic treatment
at their first visits, and beta-lactams (29.4%) and quinolones (20.5%) were the
most commonly prescribed agents. In conclusion, our study demonstrates that the
incidence of atypical pathogens is low in patients with acute bronchitis, and the
rate of antibiotic prescriptions is high.
PMID- 26425042
TI - Effect of Indacaterol on Cough and Phlegm in Chronic Obstructive Pulmonary
Disease Patients: A Meta-Analysis of Five Randomized Controlled Trials.
AB - We investigated the effects of indacaterol on cough and phlegm in patients with
stable chronic obstructive pulmonary disease (COPD). We performed a meta-analysis
with five randomized controlled trials (RCTs) of indacaterol in stable COPD
patients. The symptom severity was defined using the St. George's Respiratory
Questionnaire (SGRQ). We analyzed patients treated with 150 ug (n = 945) and 300
ug (n = 832) out of 3,325 patients who completed the SGRQ from five RCTs. After a
12-week treatment of 150 ug indacaterol, cough improvement was reported in 36.5%
(316/866) of patients treated with indacaterol vs. 32.2% (259/804) patients
treated with placebo (Relative Ratio [RR], 1.13; 95% confidence interval [CI],
0.99-1.29). Phlegm improvement was reported in 31.0% (247/798) of patients
treated with indacaterol vs. 30.6% (225/736) of patients treated with placebo
(RR, 1.01; 95% CI, 0.87-1.18). Dyspnea improvement was reported in 39.5%
(324/820) of patients treated with indacaterol vs. 31.5% (237/753) patients
treated with placebo (RR, 1.33; 95% CI, 1.03-1.71; P = 0.001, I(2) = 55.1%). Only
dyspnea improvement was significant compared to placebo even at the 300 ug
indacaterol dose. Compared to placebo, a 12-week treatment of the long-acting
beta-agonist, indacaterol might not have a significant effect on cough or phlegm
in stable COPD.
PMID- 26425043
TI - The Prognostic Value of Residual Volume/Total Lung Capacity in Patients with
Chronic Obstructive Pulmonary Disease.
AB - The prognostic role of resting pulmonary hyperinflation as measured by residual
volume (RV)/total lung capacity (TLC) in chronic obstructive pulmonary disease
(COPD) remains poorly understood. Therefore, this study aimed to identify the
factors related to resting pulmonary hyperinflation in COPD and to determine
whether resting pulmonary hyperinflation is a prognostic factor in COPD. In
total, 353 patients with COPD in the Korean Obstructive Lung Disease cohort
recruited from 16 hospitals were enrolled. Resting pulmonary hyperinflation was
defined as RV/TLC >= 40%. Multivariate logistic regression analysis demonstrated
that older age (P = 0.001), lower forced expiratory volume in 1 second (FEV1) (P
< 0.001), higher St. George Respiratory Questionnaire (SGRQ) score (P = 0.019),
and higher emphysema index (P = 0.010) were associated independently with resting
hyperinflation. Multivariate Cox regression model that included age, gender,
dyspnea scale, SGRQ, RV/TLC, and 6-min walking distance revealed that an older
age (HR = 1.07, P = 0.027), a higher RV/TLC (HR = 1.04, P = 0.025), and a shorter
6-min walking distance (HR = 0.99, P < 0.001) were independent predictors of all
cause mortality. Our data showed that older age, higher emphysema index, higher
SGRQ score, and lower FEV1 were associated independently with resting pulmonary
hyperinflation in COPD. RV/TLC is an independent risk factor for all-cause
mortality in COPD.
PMID- 26425044
TI - Risk Factors of Discharged Against Medical Advice among Adolescents Self
inflicted Injury and Attempted Suicide in the Korean Emergency Department.
AB - Suicide is a leading cause of death among Korean adolescents. Many suicide
attempting adolescents often are discharged against medical advice in the
emergency department. The aim of the present study was to determine the risk
factors for discharge against medical advice (DAMA) after self-inflicted injury
or attempted suicide in the emergency department. We extracted data on
adolescents (10-19 yr old) from the national emergency department information
system; we used data from 2007 and 2011. A total of 6,394 adolescents visited EDs
after self-inflicted injury or attempted suicide. Among these patients, the
median age was 17 yr (Interquatile range, 15-18 yr), 83.2% were between 15-19 yr
of age, and 63.3% were female. Poisoning was the most common method of attempted
suicide, while hanging and fall were the most common methods of fatality. The
rate of DAMA from the ED was 22.8%. Independent risk factors for DAMA included
female gender (odds ratio [OR], 1.49), older age adolescents (OR, 1.96),
residence in a metropolitan/large city area (OR, 1.49), and discharge at night
(OR, 1.38). These risk factors should be considered in establishing management
and counseling plans for patients discharged against medical advice by community
services and EDs.
PMID- 26425045
TI - Detection of Rotavirus Genotypes in Korea 5 Years after the Introduction of
Rotavirus Vaccines.
AB - Rotavirus (RV) is one of the most important viral etiologic agents of acute
gastroenteritis (AGE) in children. Although effective RV vaccines (RVVs) are now
used worldwide, novel genotypes and outbreaks resulting from rare genotype
combinations have emerged. This study documented RV genotypes in a Korean
population of children with AGE 5 yr after the introduction of RVV and assessed
potential genotype differences based on vaccination status or vaccine type.
Children less than 5-yr-old diagnosed with AGE between October 2012 and September
2013 admitted to 9 medical institutions from 8 provinces in Korea were
prospectively enrolled. Stool samples were tested for RV by enzyme immunoassay
and genotyped by multiplex reverse-transcription polymerase chain reaction. In
346 patients, 114 (32.9%) were RV-positive. Among them, 87 (76.3%) patients were
infected with RV alone. Eighty-six of 114 RV-positive stool samples were
successfully genotyped, and their combinations of genotypes were G1P[8] (36,
41.9%), G2P[4] (12, 14.0%), and G3P[8] (6, 7.0%). RV was detected in 27.8% of
patients in the vaccinated group and 39.8% in the unvaccinated group (P=0.035).
Vaccination history was available for 67 of 86 cases with successfully genotyped
RV-positive stool samples; RotaTeq (20, 29.9%), Rotarix (7, 10.4%), unvaccinated
(40, 59.7%). The incidence of RV AGE is lower in the RV-vaccinated group compared
to the unvaccinated group with no evidence of substitution with unusual genotype
combinations.
PMID- 26425046
TI - Neonatal Morbidities Associated with Histologic Chorioamnionitis Defined Based on
the Site and Extent of Inflammation in Very Low Birth Weight Infants.
AB - Conflicting results on the influences of histologic chorioamnionitis (HC) on
neonatal morbidities might be partly originated from using different definition
of HC. The aim of this study was to determine the relationship between HC and
neonatal morbidities using definition of HC that reflects the site and extent of
inflammation. This was a retrospective cohort study of 261 very low birth weight
(VLBW) infants admitted at a tertiary academic center. Based on the site of
inflammation, HC was categorized: any HC; amnionitis; funisitis;
amnionitis+funisitis. The extent of inflammation in each site was reflected by
sub-defining high grade (HG). The incidences of morbidities in infants with and
without HC were compared. The bronchopulmonary dysplasia (BPD) rate was
significantly higher in infants with amnionitis and the severe retinopathy of
prematurity (ROP) rate was significantly higher in infants with any HC and
funisitis. After adjustment for both gestational age and birth weight, the
respiratory distress syndrome (RDS) rate was significantly lower in infants with
all categories of HC except for HG amnionitis and HG funisitis, which are not
associated with lower RDS rate. HG amnionitis was significantly associated with
increased BPD rate but the association of HC with severe ROP disappeared. In
conclusion, HC is significantly associated with decreased RDS and HG amnionitis
with increased BPD while lacking association with other neonatal morbidities in
VLBW infants. The association with HC and neonatal morbidities differs by the
site and extent of chorioamnionitis.
PMID- 26425047
TI - Preoperative Underweight Patients with Upper Tract Urothelial Carcinoma Survive
Less after Radical Nephroureterectomy.
AB - The prognostic impact of body mass index (BMI) in patients with upper tract
urothelial carcinoma (UTUC) is an ongoing debate. Our study aimed to investigate
the prognostic role of BMI in patients treated with radical nephroureterectomy
(RNU) for UTUC from a multi-institutional Korean collaboration. We
retrospectively reviewed data from 440 patients who underwent RNU for UTUC at
four institutions in Korea. To avoid biasing the survival estimates, patients who
had previous or concomitant muscle-invasive bladder tumors were excluded. BMI was
categorized into approximate quartiles with the lowest quartile assigned to the
reference group. Kaplan-Meier and multivariate Cox regression analyses were
performed to assess the influence of BMI on survival. The lower quartile BMI
group showed significantly increased overall mortality (OM) and cancer specific
mortality (CSM) compared to the 25%-50% quartiles and upper quartile BMI groups.
Kaplan-Meier estimates showed similar results. Based on multivariate Cox
regression analysis, preoperative BMI as a continuous variable was an independent
predictor for OM and CSM. In conclusion, preoperative underweight patients with
UTUC in Korea survive less after RNU. Preoperative BMI may provide additional
prognostic information to establish risk factors.
PMID- 26425048
TI - Clinical Characteristics of the Suicide Attempters Who Refused to Participate in
a Suicide Prevention Case Management Program.
AB - Case management interventions for suicide attempters aimed at helping adjust
their social life to prevent reattempts have high nonparticipation and dropout
rates. We analyzed the clinical characteristics of the group who refused to
participate in the suicide prevention program in Korea. A total of 489 patients
with a suicide attempt who visited Uijeongbu St. Mary's Hospital, the Catholic
University of Korea, from December 2009 to December 2013 were analyzed. All
patients were divided into the participation group (n = 262) and the refusal
group (n = 227) according to their participation in the case management program.
Demographic and clinical characteristics of each group were examined. Results
showed that the refusal group had low risks for suicide in terms of risk factors
related with psychopathologies and presenting suicide behavior. That is, the
refusal group had less patients with co-morbid medical illnesses and more
patients with mild severity of depression compared to the participation group.
However, the refusal group had more interpersonal conflict, more isolation of
social integrity, and more impaired insight about suicide attempt. The results
suggest that nonparticipation in the case management program may depend upon the
patient's impaired insight about the riskiness of suicide and lack of social
support.
PMID- 26425049
TI - Effects of Repetitive Transcranial Magnetic Stimulation on Behavioral Recovery
during Early Stage of Traumatic Brain Injury in Rats.
AB - Repetitive transcranial magnetic stimulation (rTMS) is a promising technique that
modulates neural networks. However, there were few studies evaluating the effects
of rTMS in traumatic brain injury (TBI). Herein, we assessed the effectiveness of
rTMS on behavioral recovery and metabolic changes using brain magnetic resonance
spectroscopy (MRS) in a rat model of TBI. We also evaluated the safety of rTMS by
measuring brain swelling with brain magnetic resonance imaging (MRI). Twenty male
Sprague-Dawley rats underwent lateral fluid percussion and were randomly assigned
to the sham (n=10) or the rTMS (n=10) group. rTMS was applied on the fourth day
after TBI and consisted of 10 daily sessions for 2 weeks with 10 Hz frequency
(total pulses=3,000). Although the rTMS group showed an anti-apoptotic effect
around the peri-lesional area, functional improvements were not significantly
different between the two groups. Additionally, rTMS did not modulate brain
metabolites in MRS, nor was there any change of brain lesion or edema after
magnetic stimulation. These data suggest that rTMS did not have beneficial
effects on motor recovery during early stages of TBI, although an anti-apoptosis
was observed in the peri-lesional area.
PMID- 26425050
TI - Effect of Propofol and Desflurane on Immune Cell Populations in Breast Cancer
Patients: A Randomized Trial.
AB - Several factors can affect the perioperative immune function. We evaluated the
effect of propofol and desflurane anesthesia on the surgery-induced immune
perturbation in patients undergoing breast cancer surgery. The patients were
randomly assigned to receive propofol (n = 20) or desflurane (n = 20) anesthesia.
The total and differential white blood cell counts were determined with
lymphocyte subpopulations before and 1 hr after anesthesia induction and at 24 hr
postoperatively. Plasma concentrations of interleukin (IL)-2 and IL-4 were also
measured. Both propofol and desflurane anesthesia preserved the IL-2/IL-4 and
CD4(+)/CD8(+) T cell ratio. Leukocytes were lower in the propofol group than in
the desflurane group at 1 hr after induction (median [quartiles], 4.98 [3.87
6.31] vs. 5.84 [5.18-7.94] 10(3)/uL) and 24 hr postoperatively (6.92 [5.54-6.86]
vs. 7.62 [6.22-9.21] 10(3)/uL). NK cells significantly decreased 1 hr after
induction in the propofol group (0.41 [0.34-0.53] to 0.25 [0.21-0.33] 10(3)/uL),
but not in the desflurane group (0.33 [0.29-0.48] to 0.38 [0.30-0.56] 10(3)/uL).
Our findings indicate that both propofol and desflurane anesthesia for breast
cancer surgery induce a favorable immune response in terms of preservation of IL
2/IL-4 and CD4(+)/CD8(+) T cell ratio in the perioperative period. With respect
to leukocytes and NK cells, desflurane anesthesia is associated with less adverse
immune responses than propofol anesthesia during surgery for breast cancer.
(Clinical trial registration at https://cris.nih.go.kr/cris number: KCT0000939).
PMID- 26425051
TI - Relationship between Serum Uric Acid Concentration and Acute Kidney Injury after
Coronary Artery Bypass Surgery.
AB - An elevated serum concentration of uric acid may be associated with an increased
risk of acute kidney injury (AKI). The aim of this study was to investigate the
impact of preoperative uric acid concentration on the risk of AKI after coronary
artery bypass surgery (CABG). Perioperative data were evaluated from patients who
underwent CABG. AKI was defined by the AKI Network criteria based on serum
creatinine changes within the first 48 hr after CABG. Multivariate logistic
regression was utilized to evaluate the association between preoperative uric
acid and postoperative AKI. We evaluated changes in C statistic, the net
reclassification improvement, and the integrated discrimination improvement to
determine whether the addition of preoperative uric acid improved prediction of
AKI. Of the 2,185 patients, 787 (36.0%) developed AKI. Preoperative uric acid was
significantly associated with postoperative AKI (odds ratio, 1.18; 95% confidence
interval, 1.10-1.26; P<0.001). Adding uric acid levels improved the C statistic
and had significant impact on risk reclassification and integrated discrimination
for AKI. Preoperative uric acid is related to postoperative AKI and improves the
predictive ability of AKI. This finding suggests that preoperative measurement of
uric acid may help stratify risks for AKI in in patients undergoing CABG.
PMID- 26425052
TI - Common Pesticides Used in Suicide Attempts Following the 2012 Paraquat Ban in
Korea.
AB - To determine the change in pesticides used during suicide attempts after the 2012
paraquat (PQ) ban, we evaluated the annual number of suicide attempts by
pesticide ingestion between 2011 and 2014. We extracted demographic, clinical
outcome, and pesticide class data from the medical records of 1,331 patients that
attempted suicide by pesticide ingestion. Pesticides were sorted into 5 groups:
herbicides, insecticides, fungicides, other pesticides, and combined pesticides.
Each group was subdivided into various classes based on publications by the
respective Resistance Action Committees. The chi-square test for trends was used
to compare the annual incidence of categorical variables. The total number of
suicide attempts decreased each year, from 399 in 2011 to 245 in 2014.
Simultaneously, PQ ingestion decreased from 253 patients in 2011 to 60 in 2014.
The proportion of PQ to pesticides also decreased from 63.4% in 2011 to 24.5% in
2014. Furthermore, the rate of decrease in the proportion of PQ to all herbicide
categories increased by calendar year. In conclusion, there is a significant
trend in increased annual number of suicides and proportion of suicides using
glyphosates and glufosinates versus total herbicides. However, the number of
suicide attempts using glyphosate and glufosinate is lower than that using PQ.
The ratio of persons completing suicide to those attempting suicide after
pesticide ingestion has decreased every year after the PQ ban.
PMID- 26425053
TI - Dosimetric Effects of Magnetic Resonance Imaging-assisted Radiotherapy Planning:
Dose Optimization for Target Volumes at High Risk and Analytic Radiobiological
Dose Evaluation.
AB - Based on the assumption that apparent diffusion coefficients (ADCs) define high
risk clinical target volume (aCTVHR) in high-grade glioma in a cellularity
dependent manner, the dosimetric effects of aCTVHR-targeted dose optimization
were evaluated in two intensity-modulated radiation therapy (IMRT) plans.
Diffusion-weighted magnetic resonance (MR) images and ADC maps were analyzed
qualitatively and quantitatively to determine aCTVHR in a high-grade glioma with
high cellularity. After confirming tumor malignancy using the average and minimum
ADCs and ADC ratios, the aCTVHR with double- or triple-restricted water diffusion
was defined on computed tomography images through image registration. Doses to
the aCTVHR and CTV defined on T1-weighted MR images were optimized using a
simultaneous integrated boost technique. The dosimetric benefits for CTVs and
organs at risk (OARs) were compared using dose volume histograms and various
biophysical indices in an ADC map-based IMRT (IMRTADC) plan and a conventional
IMRT (IMRTconv) plan. The IMRTADC plan improved dose conformity up to 15 times,
compared to the IMRTconv plan. It reduced the equivalent uniform doses in the
visual system and brain stem by more than 10% and 16%, respectively. The ADC
based target differentiation and dose optimization may facilitate conformal dose
distribution to the aCTVHR and OAR sparing in an IMRT plan.
PMID- 26425054
TI - Therapeutic Plasmapheresis Enabling Radioactive Iodine Treatment in a Patient
with Thyrotoxicosis.
AB - Therapeutic plasma exchange (TPE) is one possible treatment for patients
resistant to conventional antithyroid drugs or requiring urgent attention for
thyrotoxicosis. We report a 35-yr-old man with thyrotoxicosis, ultimately
attributed to Graves' disease in whom antithyroid drug used initially was soon
discontinued, due to abnormal liver function, and replaced by Lugol's solution.
Three weeks later, an escape phenomenon (to Lugol's solution) was apparent, so we
performed TPE to control the thyrotoxicosis. Two courses of TPE by a centrifugal
type machine resulted in diminished levels of thyroid hormone levels, which then
rebounded after another two courses of membrane filtration type TPE. However, the
patient could be treated with radioactive iodine therapy without any
complications at present.
PMID- 26425055
TI - Predatory Publishing Practices Corrode the Credibility of Science.
PMID- 26425056
TI - Pain experience and expression in Rett syndrome: Subjective and objective
measurement approaches.
AB - Rett syndrome (RTT) is associated with myriad debilitating health issues and
significant motor and communicative impairments. Because of the former there is
concern about the possibility of recurrent and chronic pain but because of the
latter it remains difficult to determine what pain 'looks like' in RTT. This
study investigated pain experience and expression using multiple complementary
subjective and objective approaches among a clinical RTT sample. Following
informed consent, 18 participants (all female) with RTT (mean age= 12.8 years,
SD= 6.32) were characterized in terms of pain experience and interference,
typical pain expression, and elicited pain behavior during a passive range of
motion-like examination procedure. Parents completed the Dalhousie Pain Interview
(DPI; pain type, frequency, duration, intensity), the Brief Pain Inventory (BPI;
pain interference), and the Non-Communicating Children's Pain Checklist - Revised
(NCCPC-R; typical pain expression). A Pain Examination Procedure (PEP) was
conducted and scored using the Pain and Discomfort Scale (PADS). The majority of
the sample (89%) were reported to experience pain in the previous week which
presented as gastrointestinal (n=8), musculoskeletal (n=5), and seizure related
pain (n=5) that was intense (scored 0-10; M= 5.67, SD= 3.09) and long in duration
(M= 25.22 hours, SD= 53.52). Numerous pain-expressive behaviors were inventoried
(e.g., vocal, facial, mood/interaction changes) when parents reported their
child's typical pain behaviors and based on independent direct observation during
a reliably coded pain exam. This study provides subjective and objective evidence
that individuals with RTT experience recurring and chronic pain for which pain
expression appears intact.
PMID- 26425057
TI - Socio-Cultural Context and Bulling Others in Childhood.
AB - The objective of this epidemiological study was to examine, using an ecological
perspective, which individual and distal contextual factors (familial, social and
cultural) are associated with bullying other children across two different sites.
Our sample included 1,271 Puerto Rican children 10 and older years of age at
baseline residing in the South Bronx in New York and in the Standard Metropolitan
Area in San Juan and Caguas, Puerto Rico. Bullying others was assessed through
parents' and children's response to one item in the conduct disorder section of
the Diagnostic Interview Schedule for Children Version IV (DISC IV). Child,
family, social and cultural factors were examined as independent variables with
bullying others as dependent variable in hierarchical models adjusting for
gender, maternal education, poverty, single parent household and site. Prevalence
of bullying others was 15.2% in South Bronx versus 4.6% in Puerto Rico
(p<0.0001). Poor social adjustment and academic achievement, parental harsh
discipline, negative school environment, exposure to violence, peer delinquency
and level of acculturation in the child were all risk factors for bullying
others. Child acculturation accounted for site differences in rates of bullying
others. We conclude that, besides the school context, specific aspects of the
community, family, and culture influence the development of bullying perpetration
and should be targets for interventions and prevention programs. Minority youth
living in at-risk contexts may benefit from contextually sensitive preventive
interventions that address how assimilation into a high-risk context may increase
involvement in bullying perpetration.
PMID- 26425058
TI - Regional Myocutaneous Flaps for Head and Neck Reconstruction: Experience of a
Head and Neck Cancer Unit.
AB - BACKGROUND: Pectoralis major myocutaneous pedicle flap and other regional
myocutaneous pedicle flaps (RMF), despite the superiority shown by free flaps,
have remained relevant in the reconstruction of major head and neck oncologic
defects. It has continued to find relevance as the preferred reconstruction of
choice in some general head and neck reconstructive applications. While its role
has been defined in developed environment, the same cannot be said for developing
environment. The aim thus, was to review our experiences with RMFs in head and
neck reconstructions, with a view to evaluating the indications and outcomes in a
limited opportunity environment with some free flaps expertise. MATERIALS AND
METHODS: This was a retrospective cohort study from records of RMF cases
performed for head and neck reconstruction, at the study institution. Eligibility
for study inclusion comprised case cohorts with advanced head and neck diseases
requiring ablative surgery and reconstruction with pectoralis major flaps and
other RMFs. RESULTS: A total of 17 cases were treated with RMFs. 10 were
pectoralis major flaps while 7 were other RMFs. The main indications were failed
free flaps and financial constraints. No regional pedicle flap failure was
recorded; however, complication rate was 35.5% (6/17). CONCLUSION: Pectoralis
major flaps and other RMFs were very reliable option for head and neck
reconstruction. Free flap failure and financial constraints were the main
indications for RMF reconstruction indications in head and neck reconstruction in
a developing environment with some free flap expertise.
PMID- 26425059
TI - Management of Chest Drains: A National Survey on Surgeons-in-training Experience
and Practice.
AB - BACKGROUND: Chest tube insertion is a simple and sometimes life-saving procedure
performed mainly by surgical residents. However with inadequate knowledge and
poor expertise, complications may be life threatening. OBJECTIVE: We aimed to
determine the level of experience and expertise of resident surgeons in
performing tube thoracostomy. METHODOLOGY: Four tertiary institutions were
selected by simple random sampling. A structured questionnaire was administered
to 90 residents after obtaining consent. RESULTS: The majority of respondents
were between 31 and 35 years. About 10% of respondents have not observed or
performed tube thoracostomy while 77.8% of respondents performed tube
thoracostomy for the first time during residency training. The mean score was 6.2
+/- 2.2 and 59.3% of respondents exhibited good experience and practice. Rotation
through cardiothoracic surgery had an effect on the score (P = 0.034). About
80.2% always obtained consent while 50.6% always used the blunt technique of
insertion. About 61.7% of respondents routinely inserted a chest drain in the
Triangle of safety. Only 27.2% of respondents utilized different sizes of chest
tubes for different pathologies. Most respondents removed chest drains when the
output is <50 mL. Twenty-six respondents (32.1%) always monitored air leak before
removal of tubes in cases of pneumothorax. Superficial surgical site infection,
tube dislodgement, and tube blockage were the most common complications.
CONCLUSION: Many of the surgical resident lack adequate expertise in this
lifesaving procedure and they lose the opportunity to learn it as interns. There
is a need to stress the need to acquire this skill early, to further educate and
evaluate them to avoid complications.
PMID- 26425060
TI - Ethnicity and Prostate Cancer in Southern Nigeria: A Preliminary Report.
AB - INTRODUCTION: The natural history of prostate cancer varies among patients. The
aim of this study is to detect any variations in clinical and pathological
characteristics of the tumor in patients from different ethnic groups in Southern
Nigeria. PATIENTS AND METHODS: Consecutive patients who presented with features
of prostatic diseases at the Urology Units of University of Port Harcourt
Teaching Hospital, Port Harcourt and Nnamdi Azikiwe University Teaching Hospital,
Nnewi, were evaluated prospectively with history, physical examination, and
relevant investigations using a proforma. Data obtained were collated and
analyzed statistically using the Chi-square test and Microsoft Excel. RESULTS: Of
187 patients studied, 169 were analyzed. Eighty-six were Ibos, 31 Ijaws, 25
Ikwerres, and 12 Ogonis. Two were from each Etche, Urhobo, Opobo, and Effik; 4
from Andoni, and 3 Ibibio. Fifty-seven (66.3%) Ibos presented with the disease at
higher ages (70-80 years) than 19 (61.3%) Ijaws and 11 (91.7%) Ogonis. These age
differences were statistically significant with 95% and 99.9% confidence,
respectively. All cases were adenocarcinomas. Clinical features, pattern of serum
prostate-specific antigen levels, grades of the tumors, tumor metastases, and
complications were similar for all ethnic groups. Although more Ibos had tumors
with relatively more aggressive metastatic features, there was no statistical
significance. CONCLUSION: Clinical and pathological features of adenocarcinoma of
the prostate in Ibos, Ikwerres, Ijaws, and Ogonis were found to be similar.
However, Ibos presented with the disease at older ages than Ijaws and Ogonis.
PMID- 26425061
TI - Preoperative Ultrasonography as a Predictor of Difficult Laparoscopic
Cholecystectomy that Requires Conversion to Open Procedure.
AB - AIM: The present study was conducted to see whether preoperative ultrasonography
can be used as a predictor of difficult lapariscopic cholecystectomy or not.
METHODS: 50 patients of cholelithiasis, selected from surgical OPD of Rajindra
Hospital Patiala, who fulfilled all inclusion and exclusion criteria for the
study underwent elective cholecystectomy. Ultrasonography was done pre
operatively on all cases in the same setup and with same probe and patients
underwent laparoscopic cholecystectomy in same setup. RESULTS: A significant
prediction was found between ultrasonographic parameters and conversion of the
procedure to open cholecystectomy which proved that pre-operative ultrasonography
is a good predictor of difficulty in laparoscopic cholecystectomy in majority of
the cases and should be used as a screening procedure. CONCLUSION: Preoperative
ultrasonography should be used as a screening procedure as it is a good predictor
of difficulty in laparoscopic cholecystectomy in majority of the cases. It can
help surgeon to get an idea of potential difficulty that he can face in the
particular patient.
PMID- 26425062
TI - Endoscopic Evaluation of Upper and Lower Gastro-Intestinal Bleeding.
AB - INTRODUCTION: A myriad of pathologies lead to gastro-intestinal bleeding (GIB).
The common clinical presentations are hematemesis, melena, and hematochezia.
Endoscopy aids localization and treatment of these lesions. AIMS: The aim was to
study the differential diagnosis of GIB emphasizing the role of endoscopy in
diagnosis and treatment of GIB. PATIENTS AND METHODS: A prospective study of
patients with GIB referred to the Endoscopy unit of two health facilities in Port
Harcourt Nigeria from February 2012 to August 2014. The variables studied
included: Demographics, clinical presentation, risk score, endoscopic findings,
therapeutic procedure, and outcome. Data were collated and analyzed using SPSS
version 20 software. RESULTS: A total of 159 upper and lower gastro-intestinal
(GI) endoscopies were performed during the study period with 59 cases of GI
bleeding. There were 50 males and 9 females with an age range of 13-86 years
(mean age 52.4 +/- 20.6 years). The primary presentations were hematochezia,
hematemesis, and melena in 44 (75%), 9 (15%), and 6 (10%) cases, respectively.
Hemorrhoids were the leading cause of lower GIB seen in 15 cases (41%). The
majority of pathologies in upper GIB were seen in the stomach (39%): Gastritis
and benign gastric ulcer. Injection sclerotherapy was successfully performed in
the hemorrhoids and a case of gastric varices. The mortality recorded was 0%.
CONCLUSION: Endoscopy is vital in the diagnosis and treatment of GIB. Gastritis
and Haemorrhoid are the most common causes of upper and lower GI bleeding
respectively, in our environment.
PMID- 26425063
TI - The Utility of Digital Rectal Examination in Estimating Prostate Volume in a
Rural Hospital Setting.
AB - OBJECTIVES: To determine the correlation between prostate volume estimated by
digital rectal examination (DRE) and that estimated by abdominal ultrasound in
the same patients. PATIENTS AND METHODS: Men who presented to our urology
outpatient clinic with lower urinary tract symptoms were recruited in this study.
We estimated the prostate size by digital rectal examination using the sliding
scale as a guide and subsequently measured the prostate volume by transabdominal
ultrasound. RESULTS: A total of 100 patients completed this study. The mean age
was 65.6 +/- 9.84 years. The Kappa's reliability test comparing the prostate size
estimated by DRE and the prostate size measured by transabdominal ultrasound was
0.579832, the Kappa's standard error was 0.097768 and Kappa's t value was 5.93.
The Kappa's reliability test fell into good agreement range (0.4-0.75). This is
further validated by the Pearson's correlation test ascertaining correlation
between Ultrasound and DRE and generated a correlation coefficient((r)) of 0.59
(P = 0.00). This implies a high positive correlation between ultrasound estimated
prostate volume and that estimated by DRE that is statistically significant (P <
0.01). CONCLUSION: Estimation of prostate volume by digital rectal examination is
reliable. This is very important in an environment where esoteric laboratory
facilities are not readily available, and the clinician has to depend mainly on
his clinical acumen.
PMID- 26425064
TI - A Survey of the Awareness of Prostate Cancer and its Screening among Men
Attending the Outpatient Clinics of a Tertiary Health Center in Lagos, Nigeria.
AB - BACKGROUND: Prostate cancer is the most common cancer among Nigerian men and the
second most common cause of death from cancer in men worldwide. The aim of this
study was to assess the level of awareness of prostate cancer among men attending
the various outpatients' clinics of the Lagos State University Teaching Hospital,
Ikeja. MATERIALS AND METHODS: This study is a descriptive cross-sectional study.
Self-administered structured questionnaires were used to collect information from
consecutives patients attending the various outpatient clinics of the hospital.
RESULTS: One hundred and forty-six respondents with an age range of 40-80 years
participated in this study. Sixty-nine (47.3%) respondents were aware of prostate
cancer while 77 (52.7%) have never heard of the disease. Twenty (13.7%)
participants were aware of the availability of a screening test for the disease
and only 12 (8.2%) have had any form of screening for prostate cancer.
CONCLUSION: There is a low level of awareness of prostate cancer among patients
seen at our center and also level of voluntary screening for the disease is low.
PMID- 26425065
TI - Does Improvised Waterbed Reduce the Incidence of Pressure Ulcers in Patients with
Spinal Injury?
AB - BACKGROUND: Pressure ulcers are lesions caused by unrelieved pressure over bony
prominences, resulting in damage to underlying tissues. The etiology is
multifactorial including prolonged immobility. They usually complicate spinal
cord injuries with long periods of bed confinement. The use of bed replacements
markedly reduces the incidence of pressure ulcers, but the unaffordability of
these replacements in low-income countries has necessitated the need to explore
cheaper alternatives. AIM AND OBJECTIVE: The aim of this study was to ascertain
whether the use of our cheap and locally improvised waterbeds would reduce the
incidence of pressure ulcers in patients on prolonged bed confinement due to
spinal injury. METHODOLOGY: Over a 16-month period, 51 patients (age range 1-80
years) with spinal injuries were managed conservatively in our service using
improvised waterbeds in 21 (41.2%), while using the regular hospital bed/foam in
30 (58.8%). Biodata, the time interval between injury and presentation to the
hospital, nature of the injury, use of improvised waterbed and development of
pressure ulcer, were collected, collated, and analyzed. Statistical significance
was calculated with the Chi-square test. RESULTS: Most were males (98%), in the
age range of 21-30 years (25.5%), and due to fall from heights (35.3%). Of 21
patients who were managed on improvised waterbeds, 6 (28.6%) had pressure ulcers,
and of the 30 who did not use the waterbed, 17 (56.7%) developed ulcers. The
chi(2) = 3.9381, while P = 0.0472. This difference was statistically significant.
CONCLUSION: The improvised waterbed, which is much cheaper than the standard
waterbed, was observed to have significantly reduced the incidence of pressure
ulcers among our patients. Nonetheless, further studies would still be needed to
confirm this observation.
PMID- 26425066
TI - One-stage Anastomotic Urethroplasty for Traumatic Urethral Strictures. January
2004-January 2013.
AB - PURPOSE: One-stage anastomotic urethroplasty is an attractive procedure for
reconstructing the urethra following trauma. This prospective study highlights
the advantages of the procedure and outcome of treatment. MATERIALS AND METHODS:
A total of 87 patients, age range 11-68 years with a mean of 35.4 years were
included in the study. These patients were seen at two tertiary Institutions in
South East Nigeria. The stricture lengths varied between 0.8 cm and 3.2 cm. All
had suprapubic cystostomy initially followed by an end to end perineal
anastomosis after thorough work up. Preoperatively 9 (10.3%) patients had
impotence from the trauma. Postoperatively the patients were assessed with peri
catheter retrograde urethrogram, micturating cystourethrogram, and uroflowmetery.
RESULTS: All the patients were males. At 6 months, 13 out of 21 (62%) patients
who had bulbo-prostatic anastomosis and 62 out of 66 (94%) patients that had
bulbo-membranous, bulbo-bulbar anastomosis had satisfactory micturition with
urine flow rate >15 ml/s. Totally, 12 (13.8%) patients had urine flow rate of <12
ml/s. At 1-year, there were 12 re-strictures, no urinary incontinence and four
cases of a decrease in the strength of penile erection that needed no treatment.
CONCLUSION: Delayed one-stage anastomotic urethroplasty provides for decreased
incidence of postoperative morbidity, re-stricture, impotence and urinary
incontinence for most short segment posttraumatic urethral strictures.
PMID- 26425067
TI - Preoperative Prediction of Difficult Laparoscopic Cholecystectomy: A Scoring
Method.
AB - BACKGROUND: Laparoscopic cholecystectomy (LC) has become the procedure of choice
for management of symptomatic gallstone disease. At times, it is difficult and
takes longer time or has to be converted to an open procedure. This study is
undertaken to determine the predictive factors for difficult LC. AIM: The aim was
to evaluate a scoring method to predict difficult LC preoperatively. MATERIALS
AND METHODS: There were 30 cases operated by a single experienced surgeon. There
are total 15 score from history, clinical and sonological findings. Score up to 5
predicted easy, 6-10 difficult and >10 are very difficult. RESULTS: Prediction
came true in 76.4% for easy and 100% difficult cases; there were no cases with a
score above 10. The factors like previous history of hospitalization (P - 0.004),
clinically palpable gallbladder (GB) (P - 0.009), impacted GB stone (P - 0.001),
pericholecystic collection (P - 0.04), and abdominal scar due to previous
abdominal surgery (P - 0.009) were found statistically significant in predicting
difficult LC. CONCLUSION: The proposed scoring system is reliable with a
sensitivity of 76.47% and specificity of 100%.
PMID- 26425068
TI - Clinical Parameters and Challenges of Managing Cervicofacial Necrotizing
Fasciitis in a Sub-Saharan Tertiary Hospital.
AB - INTRODUCTION: Necrotizing fasciitis is a severe soft tissue infection. In our
environment, patients presenting with this infection are usually financially
incapacitated and, therefore, their management can be challenging. This paper
aimed to document the pattern and challenges encountered in the management of
cervicofacial necrotizing fasciitis (CNF) in the University College Hospital,
Ibadan. MATERIALS AND METHODS: Information such as biodata, site of infection,
systemic conditions, widest span of defect, management provided, hospital stay,
and outcome of management was prospectively collected on all patients with CNF
who presented at the Department of Oral and Maxillofacial Surgery between January
2007 and December 2013. The patients were managed according to a devised protocol
of antibiotic therapy, serial debridement and honey dressings. RESULTS: Twenty
four cases of CNF were seen. There were 9 males and 15 females while 70.9% of the
patients belonged to the low socioeconomic class. The mean span of wound defect
was 12.2 (+/-8.844) cm. The mean hospital stay was 27.8 (+/-23.1) days, and scar
formation was the most common complication encountered. CONCLUSION: Our study
represents the largest series of CNF from a Nigerian health facility presently.
The management of necrotizing fascitis in the maxillofacial region poses a
significant challenge to both the surgeon and the patient. However, the mortality
rate of CNF in our center appears comparatively low.
PMID- 26425069
TI - Early Experience with Stapled Gastrointestinal Anastomoses in a Nigerian
Hospital.
AB - BACKGROUND: Hand-sewn gastrointestinal anastomoses has been the traditional
approach to gastrointestinal anastomosis in Nigeria while stapled anastomoses are
infrequently performed in few centers. OBJECTIVES: To describe the outcome of our
initial experience with stapled gastrointestinal anastomoses in a semi-urban
patient population. PATIENTS AND METHODS: Consecutive patients who had stapled
gastrointestinal anastomoses between January 2011 and June 2014 in a Nigerian
tertiary hospital were prospectively evaluated. Indications for operation,
procedures performed and anastomoses constructed and postoperative outcome of
each patient were documented. RESULTS: Nineteen patients including seven males
and 12 females had stapled anastomoses within the period. Their ages ranged
between 41 and 68 (mean 52.5) years. Six (31.6%) Roux-en-Y gastrojejunostomies, 6
(31.6%) ileo-colic, 3 (15.8%) ileo-ileal, 2 (10.5%) colo-colic, and 2 (10.5%)
colo-anal anastomoses were performed. Indications include antral gastric cancer
in 4 (21.1%), right colon cancer 4 (21.1%), ileal perforations in 3 (15.8%) while
2 (10.5%) each had left colon cancer, common bile duct obstruction, rectal cancer
and ruptured appendix. Mean duration of operation was 108 +/- 46 min and mean
duration of postoperative stay was 5 +/- 2.6 days. No intraoperative
complications were recorded and no anastomotic leakage occurred. At a median
follow-up of 5 months no staple related stricture had occurred. CONCLUSIONS:
Stapled gastrointestinal anastomoses are associated with a good outcome in our
center. We propose a prospective, large-population randomized comparison of the
technique with hand-sewn anastomoses.
PMID- 26425070
TI - Long-Term Outcome of Endoprosthetic Replacement for Proximal Femur Giant Cell
Tumor.
AB - INTRODUCTION: Giant cell tumor (GCT) of bone is locally aggressive benign tumor
involving the epiphysis of long bones in young adults. Various treatment options
include intralesional curettage, extended curettage, wide resection, resection
and reconstruction and amputation. The main variables to be considered for
planning treatment include the site of involvement and Campanacci stage of the
tumor. Functional and oncological outcomes of these treatment options vary
widely, the predominant detrimental factor being tumor recurrence rate. AIM: A
study was conducted to evaluate the long-term oncological and functional outcome
of patients with GCT of the proximal femur that underwent tumor resection and
endoprosthetic replacement. MATERIALS AND METHODS: Eleven patients with
Campanacci stage-III GCT of proximal femur who underwent wide excision of tumor
and endoprosthesis replacement with a mean follow-up the duration of 10.6 years
were assessed using standard proforma. The treatment outcome was evaluated using
the Revised Musculoskeletal Tumor Society Rating Scale for the lower extremity.
RESULTS: At mean follow-up the duration of 10.6 years, none of the cases had
tumor recurrence, infection, prosthesis loosening or dislocation. All the
patients were community ambulators among whom eight patients were walking without
support while three patients were using a cane for support. The mean total
Musculoskeletal Tumor Society Score was 26.8 out of 30 indicating the good
outcome. CONCLUSIONS: The authors recommend that wide resection and
endoprosthetic replacement should be considered as a preferred treatment option
for proximal femur GCT as the functional, and oncological outcome is satisfactory
with this modality of treatment.
PMID- 26425071
TI - Urethroplasty Practices among Reconstructive Urologists in Nigeria.
AB - OBJECTIVES: To determine the national practice patterns in the management of male
urethral stricture disease by the open urethroplasty technique. MATERIALS AND
METHODS: A questionnaire-based national survey of Nigerian urologists was
performed during the 19(th) Annual General Meeting and Scientific Conference of
the National Association of Urological Surgeons of Nigeria, held at Ibadan,
Southwest Nigeria in 2013. RESULTS: A total of 55 respondents (67.1%) completed
the questionnaire. About 43.6% were between the ages of 40 and 49 years. Almost
41.8% had between 5 and 9 years of experience as a reconstructive urologist, and
50.9% performed 1-9 urethroplasties/year. A total of 80 responders reported
trauma as the most common etiology for their strictures. About 63.7% preferred to
treat strictures after 3-6 months of diagnosis and 67.3% of respondents preferred
the combination of retrograde urethrography and voiding cystourethrography for
the diagnosis of urethral stricture. Stenting of the urethra was done after
urethroplasty using size 16 Fr of 18 Fr silastic catheter; however, the duration
of stenting varied among urologists. About 41.8% followed up their patients for a
year, and uroflowmetry was used by 36.6% of the responders to follow-up their
patients. Stricture recurrence was the most common reported complication by 36.4%
of the respondents. CONCLUSIONS: In Nigeria, most urethral stricture diseases are
treated by open urethroplasties. Very few of these surgeries are performed
annually by young urologists. There is no uniformity in the method of diagnosis,
stenting, and follow-up after treatment.
PMID- 26425072
TI - Posterior Urethral Valves in Children: Pattern of Presentation and Outcome of
Initial Treatment in Ile-Ife, Nigeria.
AB - BACKGROUND: The management of posterior urethral valves (PUV) and its sequelae is
still a challenge to most pediatric surgeons in our environment due to late
presentation and inadequate facilities for long-term evaluation and treatment.
Despite initial successful treatment about 40% would develop chronic renal
failure. The aim is to describe the presentation, management and outcome of the
initial treatment in boys with PUV. MATERIALS AND METHODS: It is a retrospective
analysis of PUV in boys 8 years and below over a 17 years period. Demographic
characteristics, clinical features, investigations, and treatment outcome were
reviewed. RESULTS: Thirty-seven cases were analyzed. The median age was 5 months
(range from birth to 8 years). Three (8.1%) patients had prenatal ultrasound
diagnosis. The most common presentation was voiding dysfunction 37 (100%). Part
of the preoperative investigation included micturating cystourethrogram (n = 31:
83.8%) and abdomino-pelvic ultrasonography (n = 37:(100%). The mean serum
creatinine value of those who presented within the first 30 days of life and
those who presented afterwards were 325 (+/-251) umol/L and 141 (+/-100) umol/L
respectively, P = 0.003. Surgical interventions included trans-vesical excision
of valves (n = 9: 28.1%), valvotomy (n = 10: 31.3%), balloon avulsion (n = 8:
25.0%), vesicostomy (n = 4: 12.5%) and endoscopic valve avulsion (n = 1: 3.1%).
Seventeen (56.7%) patients had serum creatinine >70.4 umol/L after 1-month of
valve excision. Five (13.5%) patients had postrelief complications and 5 (13.5%)
died on admission. Ninety percentage (27/30) of patients had poor prognostic
indices. CONCLUSIONS: The initial treatment outcome was good but most had poor
prognostic factors.
PMID- 26425073
TI - Carotid Body Tumor Presenting as Parotid Swelling Misdiagnosed as Pleomorphic
Adenoma: A Rare Presentation.
AB - Carotid body tumor (CBT) also known as chemodectoma is a rare tumor of
neuroendocrine tissue of carotid body and is the most commonly seen jugular
paraganglioma. In most cases, it is benign but it can be malignant. Extra adrenal
paraganglioma is rare. We present such a rare case where unusual presentation of
chemodectoma was seen as a parotid swelling. This swelling was misdiagnosed as a
pleomorphic adenoma on clinical examination, ultrasonography, and fine-needle
aspiration cytology and superficial parotidectomy was done for the same, but on
histopathological examination it was found to be CBT presenting as a parotid
swelling.
PMID- 26425074
TI - Surgical repair of orbital fat prolapse by conjunctival fixation to the sclera.
AB - PURPOSE: The aim of the study described here was to report the outcomes of
surgery for orbital fat prolapse by conjunctival fixation to the sclera. PATIENTS
AND METHODS: Twenty-three consecutive eyes of 19 patients with orbital fat
prolapse were retrospectively reviewed. All cases were treated with the same
simple procedure without resection through conjunctival incision: fixation of
conjunctiva to the sclera with interrupted sutures of 10-0 nylon in two rows
located approximately 12-14 mm posterior to the limbus. These sutures formed an
embankment to keep the prolapsed fat posteriorly. Postoperative results were
determined by slit-lamp examination and recurrence of prolapse was defined as the
presence of orbital fat anterior to the embankment. RESULTS: During the mean
follow-up period of 19 months (range: 1-59 months), one case experienced
recurrence which required further surgery. None of the other cases experienced
recurrence, and there were no intraoperative or postoperative complications.
CONCLUSION: Conjunctival fixation to the sclera was a simple and effective
surgical technique for orbital fat prolapse, with less invasion compared to the
conventional method that requires conjunctival incision.
PMID- 26425075
TI - Clinical utility and patient considerations in the use of ofatumumab in chronic
lymphocytic leukemia.
AB - Treatment aim for chronic lymphocytic leukemia has been radically changed over
the past years from providing only a palliative approach to reaching disease
eradication and improving survival. Ofatumumab is a monoclonal humanized antibody
with peculiar in vitro and in vivo properties, at present approved for double
fludarabine and alemtuzumab refractory chronic lymphocytic leukemia. Its efficacy
in this subset of patients, who typically have an unfavorable prognosis,
facilitated its use in different Phase II and III trials. Ofatumumab as single
agent or combined with chemotherapeutic or biologic agents, led to sundry results
in the setting of both previously treated or untreated patients. Its role in
maintenance therapy is also under investigation. Further advances concerning
ofatumumab administration as first line therapy in combination with chlorambucil,
came recently from the COMPLEMENT 1 study. Results from this trial will open the
door to new perspectives of its use in treatment-naive patients. Ofatumumab was
well tolerated in almost all the studies, with the main adverse events relating
mostly to infusion reaction. Hematologic toxicity, especially neutropenia, was
also common. A significant improvement in patients' quality of life was reported
following ofatumumab treatment and this was mainly due to its effect on
constitutional symptoms. Nevertheless, some concerns remain regarding the long
term efficacy of the drug in terms of response duration and survival. The real
strength of this drug needs to be confirmed by further studies and direct
comparative trials.
PMID- 26425076
TI - Improvement of oral bioavailability of lovastatin by using nanostructured lipid
carriers.
AB - Nanostructured lipid carriers (NLCs) have been one of the systems of choice for
improving the oral bioavailability of drugs with poor water solubility. In the
present study, lovastatin (LVT)-loaded NLCs (LVT-NLCs) were successfully prepared
by hot high-pressure homogenization method with high entrapment efficiency, drug
loading, and satisfactory particle size distribution. The particles had almost
spherical and uniform shapes and were well dispersed with a particle size of <50
nm (23.5 +/- 1.6 nm) and a low polydispersity index (0.17 +/- 0.05 mV). The
result of stability showed that the LVT-NLCs dispersion maintained excellent
stability without exhibiting any aggregation, precipitation, or phase separation
at 4 degrees C for 6 months of storage. The LVT release data from all developed
solid lipid nanoparticles (SLNs) and NLCs were best fitted to a Ritger-Peppas
kinetic model (0.9832 and 0.9783 for NLCs and SLNs, respectively). This indicated
that the release of LVT from the SLNs and NLCs was due to a combination of drug
diffusion and erosion from the lipid matrix. The pharmacokinetic and
pharmacodynamic results show that LVT-NLCs were better compared to free drug,
which could be attributed to an increase in bioavailability.
PMID- 26425077
TI - Clinicopathological significance and potential drug target of CDH1 in breast
cancer: a meta-analysis and literature review.
AB - CDH1, as a tumor suppressor gene, contributes sporadic breast cancer (BC)
progression. However, the association between CDH1 hypermethylation and BC, and
its clinicopathological significance remains unclear. We conducted a meta
analysis to investigate the relationship between the CDH1 methylation profile and
the major clinicopathological features. A detailed literature was searched
through the electronic databases PubMed, Web of ScienceTM, and EMBASETM for
related research publications. The data were extracted and assessed by two
reviewers independently. Odds ratios (ORs) with corresponding confidence
intervals (CIs) were calculated and summarized respectively. The frequency of
CDH1 methylation was significantly higher in invasive ductal carcinoma than in
normal breast tissues (OR =5.83, 95% CI 3.76-9.03, P<0.00001). CDH1
hypermethylation was significantly higher in estrogen receptor (ER)-negative BC
than in ER-positive BC (OR =0.62, 95% CI 0.43-0.87, P=0.007). In addition, we
found that the CDH1 was significantly methylated in HER2-negative BC than in HER2
positive BC (OR =0.26, 95% CI 0.15-0.44, P<0.00001). However, CDH1 methylation
frequency was not associated with progesterone receptor (PR) status, or with
grades, stages, or lymph node metastasis of BC patients. Our results indicate
that CDH1 hypermethylation is a potential novel drug target for developing
personalized therapy. CDH1 hypermethylation is strongly associated with ER
negative and HER2-negative BC, respectively, suggesting CDH1 methylation status
could contribute to the development of novel therapeutic approaches for the
treatment of ER-negative or HER2-negative BC with aggressive tumor biology.
PMID- 26425078
TI - Effects of exercise intensity on postexercise hypotension after resistance
training session in overweight hypertensive patients.
AB - Among all nonpharmacological treatments, aerobic or resistance training (RT) has
been indicated as a significantly important strategy to control hypertension.
However, postexercise hypotension responses after intensity alterations in RT are
not yet fully understood. The purpose of this study was to compare the outcomes
of differing intensities of RT on hypertensive older women. Twenty hypertensive
older women participated voluntarily in this study. After a maximum voluntary
contraction test (one repetition maximum) and determination of 40% and 80%
experimental loads, the protocol (3 sets/90" interset rest) was performed in a
single session with the following exercises: leg press, leg extension, leg curl,
chest press, elbow flexion, elbow extension, upper back row, and abdominal
flexion. Systolic and diastolic blood pressures were evaluated at rest, during
exercise peak, and after 5, 10, 15, 30, 45, and 60 minutes of exercise and
compared to the control. Both experimental loads were effective (P<0.01) in
promoting postexercise systolic hypotension (mmHg) compared to controls, after
30, 45, and 60 minutes, respectively, at 40% (113+/-2, 112+/-4, and 110+/-3 mmHg)
and 80% (111+/-3, 111+/-4, and 110+/-4 mmHg). Both procedures promoted
hypotension with similar systolic blood pressures (40%: -11%+/-1.0% and 80%:
13%+/-0.5%), mean arterial blood pressures (40%: -12%+/-5.5% and 80%: -12%+/
3.4%), and rate-pressure products (40%: -15%+/-2.1% and 80%: -17%+/-2.4%)
compared to control measures (systolic blood pressure: 1%+/-1%, mean arterial
blood pressure:? 0.6%+/-1.5%, rate-pressure product: 0.33%+/-1.1%). No
differences were found in diastolic blood pressure and heart rate measures. In
conclusion, hypertensive older women exhibit postexercise hypotension
independently of exercise intensity without expressed cardiovascular overload
during the session.
PMID- 26425079
TI - History of falls, gait, balance, and fall risks in older cancer survivors living
in the community.
AB - Older cancer survivors may be predisposed to falls because cancer-related
sequelae affect virtually all body systems. The use of a history of falls, gait
speed, and balance tests to assess fall risks remains to be investigated in this
population. This study examined the relationship of previous falls, gait, and
balance with falls in community-dwelling older cancer survivors. At the baseline,
demographics, health information, and the history of falls in the past year were
obtained through interviewing. Participants performed tests including gait speed,
Balance Evaluation Systems Test, and short-version of Activities-specific Balance
Confidence scale. Falls were tracked by mailing of monthly reports for 6 months.
A "faller" was a person with >=1 fall during follow-up. Univariate analyses,
including independent sample t-tests and Fisher's exact tests, compared baseline
demographics, gait speed, and balance between fallers and non-fallers. For
univariate analyses, Bonferroni correction was applied for multiple comparisons.
Baseline variables with P<0.15 were included in a forward logistic regression
model to identify factors predictive of falls with age as covariate. Sensitivity
and specificity of each predictor of falls in the model were calculated.
Significance level for the regression analysis was P<0.05. During follow-up, 59%
of participants had one or more falls. Baseline demographics, health information,
history of falls, gaits speed, and balance tests did not differ significantly
between fallers and non-fallers. Forward logistic regression revealed that a
history of falls was a significant predictor of falls in the final model (odds
ratio =6.81; 95% confidence interval =1.594-29.074) (P<0.05). Sensitivity and
specificity for correctly identifying a faller using the positive history of
falls were 74% and 69%, respectively. Current findings suggested that for
community-dwelling older cancer survivors with mixed diagnoses, asking about the
history of falls may help detect individuals at risk of falling.
PMID- 26425081
TI - Targeting delivery of Radix Ophiopogonis polysaccharide to ischemic/reperfused
rat myocardium by long-circulating macromolecular and liposomal carriers.
AB - Drug delivery to ischemic myocardium is an enormous challenge. This work aimed to
characterize cardiac delivery behaviors of mono-polyethylene glycosylated
(PEGylated) conjugates and long-circulating liposomes (L-Lps) with Radix
Ophiopogonis polysaccharide (ROP) as drug. The results showed that compared to
native ROP, 32-, 52-, and 45-fold increases in blood half-life were achieved by
20-kDa PEG mono-modified ROP (P(20k)-R), 40-kDa PEG mono-modified ROP (P(40k)-R),
and ROP-loaded L-Lp, respectively. With comparable blood pharmacokinetics, ROP
loaded L-Lp showed both significantly higher targeting efficacy and drug exposure
in infarcted myocardium than P(40k)-R. With regard to P(20k)-R, both its
targeting efficacy and its level in infarcted myocardium at 3 hours postdose were
comparable to P(40k)-R, but its level in blood and myocardium reduced obviously
faster. As a whole, the results indicate that both loading in L-Lps and mono
PEGylation are effective in targeting drug to ischemic myocardium, but the former
appears to induce stronger effects.
PMID- 26425080
TI - Delivery of DNAzyme targeting aurora kinase A to inhibit the proliferation and
migration of human prostate cancer.
AB - Herein, a polyethylenimine derivative N-acetyl-L-leucine-polyethylenimine (N-Ac-L
Leu-PEI) was employed as a carrier to achieve the delivery of DNAzyme targeting
aurora kinase A using PC-3 cell as a model. Flow cytometry and confocal laser
scanning microscopy demonstrated that the derivative could realize the cellular
uptake of nanoparticles in an energy-dependent and clathrin-mediated pathway and
obtain a high DNAzyme concentration in the cytoplasm through further endosomal
escape. After DNAzyme transfection, expression level of aurora kinase A would be
downregulated at the protein level. Meanwhile, the inhibition of cell
proliferation was observed through 3-(4,5-Dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide and cell colony formation assay, attributing to the
activation of apoptosis and cell cycle arrest. Through flow cytometric analysis,
an early apoptotic ratio of 25.93% and G2 phase of 22.58% has been detected after
N-Ac-L-Leu-PEI-mediated DNAzyme transfection. Finally, wound healing and
Transwell migration assay showed that DNAzyme transfection could efficiently
inhibit the cell migration. These results demonstrated that N-Ac-L-Leu-PEI could
successfully mediate the DNAzyme delivery and downregulate the expression level
of aurora kinase A, triggering a significant inhibitory effect of excessive
proliferation and migration of tumor cells.
PMID- 26425082
TI - Cytotoxicity and physicochemical characterization of iron-manganese-doped
sulfated zirconia nanoparticles.
AB - Iron-manganese-doped sulfated zirconia nanoparticles with both Lewis and Bronsted
acidic sites were prepared by a hydrothermal impregnation method followed by
calcination at 650 degrees C for 5 hours, and their cytotoxicity properties
against cancer cell lines were determined. The characterization was carried out
using X-ray diffraction, thermogravimetric analysis, Fourier transform infrared
spectroscopy, Brauner-Emmett-Teller (BET) surface area measurements, X-ray
fluorescence, X-ray photoelectron spectroscopy, zeta size potential, and
transmission electron microscopy (TEM). The cytotoxicity of iron-manganese-doped
sulfated zirconia nanoparticles was determined using 3-(4,5-dimethylthiazol-2-yl)
2,5-diphenyltetrazolium bromide (MTT) assays against three human cancer cell
lines (breast cancer MDA-MB231 cells, colon carcinoma HT29 cells, and
hepatocellular carcinoma HepG2 cells) and two normal human cell lines (normal
hepatocyte Chang cells and normal human umbilical vein endothelial cells
[HUVECs]). The results suggest for the first time that iron-manganese-doped
sulfated zirconia nanoparticles are cytotoxic to MDA-MB231 and HepG2 cancer cells
but have less toxicity to HT29 and normal cells at concentrations from 7.8 MUg/mL
to 500 MUg/mL. The morphology of the treated cells was also studied, and the
results supported those from the cytotoxicity study in that the nanoparticle
treated HepG2 and MDA-MB231 cells had more dramatic changes in cell morphology
than the HT29 cells. In this manner, this study provides the first evidence that
iron-manganese-doped sulfated zirconia nanoparticles should be further studied
for a wide range of cancer applications without detrimental effects on healthy
cell functions.
PMID- 26425083
TI - Endothelial cell-targeted pVEGF165 polyplex plays a pivotal role in inhibiting
intimal thickening after vascular injury.
AB - Upregulation of vascular endothelial growth factor (VEGF) expression can inhibit
intimal thickening after vascular injury. However, the lack of efficient gene
delivery systems leads to insufficient VEGF expression, which prevents its
application in gene therapy. In the present study, to improve the delivery of the
plasmid vector with the VEGF gene (pVEGF165) to the injured vessel wall, we
explored the potentially important difference between endothelial cell-targeted
and nontargeted polymeric carriers. The alphavbeta3 integrin is overexpressed on
activated endothelial cells but not on normal quiescent vessels. In this study,
CDG2-cRGD, synthesized by conjugating an alphavbeta3 integrin-binding cyclic
arginylglycylaspartic acid (cRGD) peptide with the Generation 2 polycation
polyamidoamine (PAMAMG2)-g-cyclodextrin (termed as CDG2), was developed as a
targetable carrier. It was observed that the specific integrin-ligand
interactions greatly enhanced cellular internalization of CDG2-cRGD in human
umbilical vein endothelial cells (HUVECs), which are notoriously difficult to
transfect. Consequently, HUVECs were found to show remarkably high levels of
VEGF165 expression induced by the CDG2-cRGD polyplex. Interestingly, VEGF165
overexpression in vivo was more complex than that in vitro, and in vivo assays
demonstrated that the stimulus response to balloon injury in arteries could
obviously upregulate VEGF165 expression in the saline-treated group, although it
was not enough to prevent intimal thickening. In gene-transfected groups,
intravascular delivery of pVEGF165 with the CDG2-cRGD polyplex into rabbits after
vascular injury resulted in a significant inhibition of intimal thickening at 4
weeks, whereas the low therapeutic efficacy in the nontargeted CDG2-treated group
was only comparable to that in the saline-treated group. It is becoming clear
that the conflicting results of VEGF165 gene therapy in two gene-transfected
groups are reflective of the pivotal role of the cRGD-conjugated carriers in
achieving the beneficial therapeutic effects of vascular gene therapy.
PMID- 26425084
TI - Preparation and characterization of anti-HIV nanodrug targeted to microfold cell
of gut-associated lymphoid tissue.
AB - The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life
threatening diseases in the world. The introduction of highly active
antiretroviral therapy has significantly reduced disease morbidity and mortality.
However, most of the drugs have variable penetrance into viral reservoir sites,
including gut-associated lymphoid tissue (GALT). Being the largest lymphoid
organ, GALT plays a key role in early HIV infection and host-pathogen
interaction. Many different treatment options have been proposed to eradicate the
virus from GALT. However, it becomes difficult to deliver traditional drugs to
the GALT because of its complex physiology. In this regard, we developed a
polymer-based Pluronic nanocarrier containing anti-HIV drug called efavirenz
(EFV) targeting Microfold cells (M-cells) in the GALT. M-cells are specialized
epithelial cells that are predominantly present in the GALT. In this work, we
have exploited this paracellular transport property of M-cells for targeted
delivery of Pluronic nanocarrier tagged EFV, bioconjugated with anti-M-cell
specific antibodies to the GALT (nanodrug). Preliminary characterization showed
that the nanodrug (EFV-F12-COOH) is of 140 nm size with 0.3 polydispersion index,
and the zeta potential of the particles was -19.38+/-2.2 mV. Further, drug
dissolution study has shown a significantly improved sustained release over free
drugs. Binding potential of nanodrug with M-cell was also confirmed with
fluorescence microscopy and in vitro uptake and release studies. The anti-HIV
activity of the nanodrug was also significantly higher compared to that of free
drug. This novel formulation was able to show sustained release of EFV and
inhibit the HIV-1 infection in the GALT compared to the free drug. The present
study has potential for our in vivo targeted nanodrug delivery system by
combining traditional enteric-coated capsule technique via oral administration.
PMID- 26425085
TI - Development, characterization, and skin delivery studies of related
ultradeformable vesicles: transfersomes, ethosomes, and transethosomes.
AB - Ultradeformable vesicles (UDV) have recently become a promising tool for the
development of improved and innovative dermal and transdermal therapies. The aim
of this work was to study three related UDV: transfersomes, ethosomes, and
transethosomes for the incorporation of actives of distinct polarities, namely,
vitamin E and caffeine, and to evaluate the effect of the carrier on skin
permeation and penetration. These actives were incorporated in UDV formulations
further characterized for vesicles imaging by transmission electron microscopy;
mean vesicle size and polydispersity index by photon correlation spectroscopy;
zeta potential by laser-Doppler anemometry; deformability by pressure-driven
transport; and incorporation efficiency (IE) after actives quantification by high
performance liquid chromatography. Topical delivery studies were performed in
order to compare UDV formulations regarding the release, skin permeation, and
penetration profiles. All UDV formulations showed size values within the expected
range, except transethosomes prepared by "transfersomal method", for which size
was smaller than 100 nm in contrast to that obtained for vesicles prepared by
"ethosomal method". Zeta potential was negative and higher for formulations
containing sodium cholate. The IE was much higher for vitamin E- than caffeine
loaded UDV as expected. For flux measurements, the following order was obtained:
transethosomes (TE) > ethosomes (E) >= transfersomes (T). This result was
consistent with the release and skin penetration profiles for Vitamin E-loaded
UDV. However, the releasing results were totally the opposite for caffeine-loaded
UDV, which might be explained by the solubility and thermodynamic activity of
this active in each formulation instead of the UDV deformability attending to the
higher non-incorporated fraction of caffeine. Anyway, a high skin penetration and
permeation for all caffeine-loaded UDV were obtained. Transethosomes were more
deformable than ethosomes and transfersomes due to the presence of both ethanol
and surfactant in their composition. All these UDV were suitable for a deeper
skin penetration, especially transethosomes.
PMID- 26425086
TI - Neurite outgrowth stimulatory effects of myco synthesized AuNPs from Hericium
erinaceus (Bull.: Fr.) Pers. on pheochromocytoma (PC-12) cells.
AB - BACKGROUND: Hericium erinaceus has been reported to have a wide range of
medicinal properties such as stimulation of neurite outgrowth, promotion of
functional recovery of axonotmetic peroneal nerve injury, antioxidant,
antihypertensive, and antidiabetic properties. In recent years, the green
synthesis of gold nanoparticles (AuNPs) has attracted intense interest due to the
potential use in biomedical applications. The aim of this study was to
investigate the effects of AuNPs from aqueous extract of H. erinaceus on neurite
outgrowth of rat pheochromocytoma (PC-12) cells. METHODS: The formation of AuNPs
was characterized by UV-visible spectrum, energy dispersive X-ray (EDX), field
emission scanning electron microscope (FESEM), transmission electron microscopy
(TEM), particle size distribution, and Fourier transform-infrared spectroscopy
(FTIR). Furthermore, the neurite extension study of synthesized AuNPs was
evaluated by in vitro assay. RESULTS: The AuNPs exhibited maximum absorbance
between 510 and 600 nm in UV-visible spectrum. FESEM and TEM images showed the
existence of nanoparticles with sizes of 20-40 nm. FTIR measurements were carried
out to identify the possible biomolecules responsible for capping and efficient
stabilization of the nanoparticles. The purity and the crystalline properties
were confirmed by EDX diffraction analysis, which showed strong signals with
energy peaks in the range of 2-2.4 keV, indicating the existence of gold atoms.
The synthesized AuNPs showed significant neurite extension on PC-12 cells. Nerve
growth factor 50 ng/mL was used as a positive control. Treatment with different
concentrations (nanograms) of AuNPs resulted in neuronal differentiation and
neuronal elongation. AuNPs induced maximum neurite outgrowth of 13% at 600 ng/mL
concentration. CONCLUSION: In this study, the AuNPs synthesis was achieved by a
simple, low-cost, and rapid bioreduction approach. AuNPs were shown to have
potential neuronal differentiation and stimulated neurite outgrowth. The water
soluble bioconstituents could be responsible for the neuroactivity. This is the
first report for the biosynthesis of AuNPs using the hot aqueous extract of H.
erinaceus.
PMID- 26425087
TI - Probing insulin bioactivity in oral nanoparticles produced by ultrasonication
assisted emulsification/internal gelation.
AB - Alginate-dextran sulfate-based particles obtained by emulsification/internal
gelation technology can be considered suitable carriers for oral insulin
delivery. A rational study focused on the emulsification and particle recovery
steps was developed in order to reduce particles to the nanosize range while
keeping insulin bioactivity. There was a decrease in size when ultrasonication
was used during emulsification, which was more pronounced when a cosurfactant was
added. Ultrasonication add-on after particle recovery decreased aggregation and
led to a narrower nanoscale particle-size distribution. Insulin encapsulation
efficiency was 99.3%+/-0.5%, attributed to the strong pH-stabilizing
electrostatic effect between insulin and nanoparticle matrix polymers.
Interactions between these polymers and insulin were predicted using molecular
modeling studies through quantum mechanics calculations that allowed for
prediction of the interaction model. In vitro release studies indicated well
preserved integrity of nanoparticles in simulated gastric fluid. Circular
dichroism spectroscopy proved conformational stability of insulin and Fourier
transform infrared spectroscopy technique showed rearrangements of insulin
structure during processing. Moreover, in vivo biological activity in diabetic
rats revealed no statistical difference when compared to nonencapsulated insulin,
demonstrating retention of insulin activity. Our results demonstrate that
alginate-dextran sulfate-based nanoparticles efficiently stabilize the loaded
protein structure, presenting good physical properties for oral delivery of
insulin.
PMID- 26425088
TI - Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible
branched copolymer nanocontrast agents.
AB - Branched copolymer nanoparticles (D(h) =20-35 nm) possessing 1,4,7, 10
tetraazacyclododecane-N,N',N",N'''-tetraacetic acid macrocycles within their
cores have been synthesized and applied as magnetic resonance imaging (MRI)
nanosized contrast agents in vivo. These nanoparticles have been generated from
novel functional monomers via reversible addition-fragmentation chain transfer
polymerization. The process is very robust and synthetically straightforward.
Chelation with gadolinium and preliminary in vivo experiments have demonstrated
promising characteristics as MRI contrast agents with prolonged blood retention
time, good biocompatibility, and an intravascular distribution. The ability of
these nanoparticles to perfuse and passively target tumor cells through the
enhanced permeability and retention effect is also demonstrated. These novel
highly functional nanoparticle platforms have succinimidyl ester-activated
benzoate functionalities within their corona, which make them suitable for future
peptide conjugation and subsequent active cell-targeted MRI or the conjugation of
fluorophores for bimodal imaging. We have also demonstrated that these branched
copolymer nanoparticles are able to noncovalently encapsulate hydrophobic guest
molecules, which could allow simultaneous bioimaging and drug delivery.
PMID- 26425090
TI - Today's diverse nano-theranostic applications and tomorrow's promises.
PMID- 26425089
TI - Microwave-assisted fibrous decoration of mPE surface utilizing Aloe vera extract
for tissue engineering applications.
AB - Developing multifaceted, biocompatible, artificial implants for tissue
engineering is a growing field of research. In recent times, several works have
been reported about the utilization of biomolecules in combination with synthetic
materials to achieve this process. Accordingly, in this study, the ability of an
extract obtained from Aloe vera, a commonly used medicinal plant in influencing
the biocompatibility of artificial material, is scrutinized using metallocene
polyethylene (mPE). The process of coating dense fibrous Aloe vera extract on the
surface of mPE was carried out using microwaves. Then, several physicochemical
and blood compatibility characterization experiments were performed to disclose
the effects of corresponding surface modification. The Fourier transform infrared
spectrum showed characteristic vibrations of several active constituents
available in Aloe vera and exhibited peak shifts at far infrared regions due to
aloe-based mineral deposition. Meanwhile, the contact angle analysis demonstrated
a drastic increase in wettability of coated samples, which confirmed the presence
of active components on glazed mPE surface. Moreover, the bio-mimic structure of
Aloe vera fibers and the influence of microwaves in enhancing the coating
characteristics were also meticulously displayed through scanning electron
microscopy micrographs and Hirox 3D images. The existence of nanoscale roughness
was interpreted through high-resolution profiles obtained from atomic force
microscopy. And the extent of variations in irregularities was delineated by
measuring average roughness. Aloe vera-induced enrichment in the hemocompatible
properties of mPE was established by carrying out in vitro tests such as
activated partial thromboplastin time, prothrombin time, platelet adhesion, and
hemolysis assay. In conclusion, the Aloe vera-glazed mPE substrate was inferred
to attain desirable properties required for multifaceted biomedical implants.
PMID- 26425091
TI - Magnetic microparticle-based multimer detection system for the detection of prion
oligomers in sheep.
AB - Transmissible spongiform encephalopathies (TSEs) are zoonotic fatal
neurodegenerative diseases in animals and humans. TSEs are commonly known as
bovine spongiform encephalopathy in cattle, scrapie in sheep and goats, chronic
wasting disease in cervids, and Creutzfeldt-Jakob disease in humans. The putative
transmissible agents are infectious prion proteins (PrP(Sc)), which are formed by
the conversion of the normal prion protein on the glycoprotein cell surface in
the presence of other PrP(Sc). Reports of the transmission of TSEs through blood
raised considerable concern about the safety of blood and blood products. To
address this issue, many laboratories attempted to develop a sensitive and
accurate blood diagnostic test to detect PrP(Sc). Previously, we reported that,
compared to normal controls, the multimer detection system (MDS) was more
efficient in detecting PrP(Sc) in infected hamster brain homogenate, mouse plasma
spiked with purified PrP(Sc) from scrapie mouse brain, and scrapie-infected
hamster plasmas. MDS differentiates prion multimers from the cellular monomer
through the multimeric expression of epitopes on prion multimers, in contrast to
the monomeric form. In this study, MDS detected PrP(Sc) in plasma samples from
scrapie-infected sheep expressing clinical symptoms, demonstrating 100%
sensitivity and specificity in these samples. Plasma samples from asymptomatic
lambs at the preclinical stage (8-month-old naturally infected offspring of
scrapie-infected parents expressing a highly susceptible genotype) tested
positive with 50% sensitivity and 100% specificity. In the first of two coded
analyses using clinical scrapie-infected sheep and normal healthy samples, MDS
successfully identified all but one of the clinical samples with 92% sensitivity
and 100% specificity. Similar results were obtained in the second coded analysis
using preclinical samples. MDS again successfully identified all but one of the
samples with 87% sensitivity and 100% specificity. The false-negative sample was
subjected to a protease pretreatment. In conclusion, MDS could accurately detect
scrapie in plasma samples at both preclinical and clinical stages. From these
studies, we conclude that MDS could be a promising tool for the early diagnosis
of TSEs from blood samples.
PMID- 26425093
TI - Comparative hyperthermia effects of silica-gold nanoshells with different surface
coverage of gold clusters on epithelial tumor cells.
AB - Silica-gold nanoshell (SGNS), which is a silica core surrounded by a gold layer,
was synthesized by seed-mediated coalescence of gold clusters in an electroless
plating solution. SGNS variations with different surface coverage of gold
clusters were prepared by adjusting the amounts of gold salts in the presence of
formaldehyde-reducing agents. Fully covered SGNS (f-SGNS) with connected gold
clusters exhibited stronger intensity and more redshift of plasmon bands located
around 820 nm than those of partially covered SGNS (p-SGNS) with disconnected
gold clusters. Upon irradiation with near-infrared light (30 W/cm(2), 700-800
nm), f-SGNS caused a larger hyperthermia effect, generating a large temperature
change (DeltaT =42 degrees C), as compared to the relatively small temperature
change (DeltaT =24 degrees C) caused by p-SGNS. The therapeutic antibody,
ErbituxTM (ERB), was further conjugated to SGNS for specific tumor cell
targeting. The f-ERB-SGNS showed excellent therapeutic efficacy based on the
combined effect of both the therapeutic antibody and the full hyperthermia dose
under near-infrared irradiation. Thus, SGNS with well-controlled surface
morphology of gold shells may be applicable for near-infrared-induced
hyperthermia therapy with tunable optical properties.
PMID- 26425094
TI - An innovative intervention for the treatment of cognitive impairment-Emisymmetric
bilateral stimulation improves cognitive functions in Alzheimer's disease and
mild cognitive impairment: an open-label study.
AB - BACKGROUND AND AIMS: In the last decade, the development of different methods of
brain stimulation by electromagnetic fields (EMF) provides a promising
therapeutic tool for subjects with impaired cognitive functions. Emisymmetric
bilateral stimulation (EBS) is a novel and innovative EMF brain stimulation,
whose working principle is to introduce very weak noise-like stimuli through EMF
to trigger self-arrangements in the cortex of treated subjects, thereby improving
cognitive faculties. The aim of this pilot study was to investigate in patients
with cognitive impairment the effectiveness of EBS treatment with respect to
global cognitive function, episodic memory, and executive functions. METHODS:
Fourteen patients with cognitive decline (six with mild cognitive impairment and
eight with Alzheimer's disease) underwent three EBS applications per week to both
the cerebral cortex and auricular-specific sites for a total of 5 weeks. At
baseline, after 2 weeks and 5 weeks, a neuropsychological assessment was
performed through mini-mental state examination, free and cued selective
reminding tests, and trail making test. As secondary outcomes, changes in
behavior, functionality, and quality of life were also evaluated. RESULTS: After
5 weeks of standardized EBS therapy, significant improvements were observed in
all neurocognitive assessments. Mini-mental state examination score significantly
increased from baseline to end treatment (+3.19, P=0.002). Assessment of episodic
memory showed an improvement both in immediate and delayed recalls (immediate
recall =+7.57, P=0.003; delayed recall =+4.78, P<0.001). Executive functions
significantly improved from baseline to end stimulation (trail making test A
53.35 seconds; P=0.001). Of note, behavioral disorders assessed through
neuropsychiatric inventory significantly decreased (-28.78, P<0.001). The
analysis concerning the Alzheimer's disease and mild cognitive impairment group
confirmed a significant improvement of cognitive functions and behavior after EBS
treatment. CONCLUSION: This pilot study has shown EBS to be a promising,
effective, and safe tool to treat cognitive impairment, in addition to the drugs
presently available. Further investigations and controlled clinical trials are
warranted.
PMID- 26425092
TI - Targeting cancer stem cells by using the nanoparticles.
AB - Cancer stem cells (CSCs) have been shown to be markedly resistant to conventional
cancer treatments such as chemotherapy and radiation therapy. Therefore,
therapeutic strategies that selectively target CSCs will ultimately lead to
better cancer treatments. Currently, accessible conventional therapeutic agents
mainly eliminate the bulk tumor but do not eliminate CSCs. Therefore, the
discovery and improvement of CSC-targeting therapeutic agents are necessary.
Nanoparticles effectively inhibit multiple types of CSCs by targeting specific
signaling pathways (Wnt/beta-catenin, Notch, transforming growth factor-beta, and
hedgehog signaling) and/or specific markers (aldehyde dehydrogenases, CD44, CD90,
and CD133) critically involved in CSC function and maintenance. In this review
article, we summarized a number of findings to provide current information about
their therapeutic potential of nanoparticles in various cancer cell types and
CSCs.
PMID- 26425095
TI - Intractable and highly active relapsing multiple sclerosis - role of alemtuzumab.
AB - Alemtuzumab is a humanized recombinant monoclonal antibody that was recently
approved by the US Food and Drug Administration and the European Medicines Agency
for the management of relapsing forms of multiple sclerosis (MS). It has been
utilized for the management of chronic lymphocytic leukemia, bone marrow and
renal transplantation, or graft versus host disease. Because of its
immunomodulatory properties, it was brought into clinical development in MS. One
Phase II (CAMMS223) and two Phase III clinical trials (CARE-MSI and -II) have
evaluated the safety and efficacy of alemtuzumab in patients with relapsing
remitting MS. Even though its efficacy profile and long-lasting effect have
attracted much interest among physicians and patients, it has significant
potential adverse effects that may limit its use to patients with active disease.
Here, we review the history of drug development of alemtuzumab. Furthermore, we
outline the postulated mechanisms of action, clinical evidence, and safety of
alemtuzumab for its use as a disease-modifying agent in active and highly active
MS.
PMID- 26425096
TI - Anatomical and functional brain abnormalities in unmedicated major depressive
disorder.
AB - BACKGROUND: Using magnetic resonance imaging (MRI) and resting-state functional
magnetic resonance imaging (rsfMRI) to explore the mechanism of brain structure
and function in unmedicated patients with major depressive disorder (MDD).
PATIENTS AND METHODS: Fifty patients with MDD and 50 matched healthy control
participants free of psychotropic medication underwent high-resolution structural
and rsfMRI scanning. Optimized diffeomorphic anatomical registration through
exponentiated lie algebra and the Data Processing Assistant for rsfMRI were used
to find potential differences in gray-matter volume (GMV) and regional
homogeneity (ReHo) between the two groups. A Pearson correlation model was used
to analyze associations of morphometric and functional changes with clinical
symptoms. RESULTS: Compared to healthy controls, patients with MDD showed
significant GMV increase in the left posterior cingulate gyrus and GMV decrease
in the left lingual gyrus (P<0.001, uncorrected). In ReHo analysis, values were
significantly increased in the left precuneus and decreased in the left putamen
(P<0.001, uncorrected) in patients with MDD compared to healthy controls. There
was no overlap between anatomical and functional changes. Linear correlation
suggested no significant correlation between mean GMV values within regions with
anatomical abnormality and ReHo values in regions with functional abnormality in
the patient group. These changes were not significantly correlated with symptom
severity. CONCLUSION: Our study suggests a dissociation pattern of brain regions
with anatomical and functional alterations in unmedicated patients with MDD,
especially with regard to GMV and ReHo.
PMID- 26425097
TI - The MGuard coronary stent: safety, efficacy, and clinical utility.
AB - Atheromatous and thrombotic embolization during percutaneous coronary
revascularization is a feared complication that may cause impaired myocardial
reperfusion even with a patent epicardial vessel. The MGuard stent is a cobalt
chromium bare metal stent with a porous net attached to its outer surface that
has been designed to prevent thrombus fragmentation and distal embolization
during stent implantation. This review summarizes the available evidence
supporting the use of the MGuard stent in different scenarios such as lesions
with high thrombus burden, saphenous vein graft interventions, coronary
perforations, or carotid lesions.
PMID- 26425099
TI - Comparing two assays for clinical genomic profiling: the devil is in the data
[Letter of clarification].
PMID- 26425098
TI - A comparative cohort study of totally laparoscopic and open aortobifemoral bypass
for the treatment of advanced atherosclerosis.
AB - BACKGROUND: Totally laparoscopic aortobifemoral bypass (LABF) procedure has been
shown to be feasible for the treatment of advanced aortoiliac occlusive disease
(AIOD). This study compares the LABF with the open aortobifemoral bypass (OABF)
operation. METHODS: In this prospective comparative cohort study, 50 consecutive
patients with type D atherosclerotic lesions in the aortoiliac segment were
treated with an LABF operation. The group was compared with 30 patients who were
operated on with the OABF procedure for the same disease and time period. We had
an explanatory strategy, and our research hypothesis was to compare the two
surgical procedures based on a composite event (all-cause mortality, graft
occlusion, and systemic morbidity). Stratification analysis was performed by
using the Mantel-Haenszel method with the patient-time model. Cox multivariate
regression method was used to adjust for confounding effect after considering the
proportional hazard assumption. Cox proportional cause-specific hazard regression
model was used for competing risk endpoint. RESULTS: There was a higher frequency
of comorbidity in the OABF group. A significant reduction of composite event, 82%
(hazard ratio 0.18; 95% CI 0.08-0.42, P=0.0001) was found in the LABF group when
compared with OABF group, during a median follow-up time period of 4.12 years
(range from 1 day to 9.32 years). In addition, less operative bleeding and
shorter length of hospital stay were observed in the LABF group when compared
with the OABF group. All components of the composite event showed the same
positive effect in favor of LABF procedure. CONCLUSION: LABF for the treatment of
AIOD, Trans-Atlantic Inter-Society Consensus II type D lesions, seems to result
in a less composite event when compared with the OABF procedure. To conclude, our
results need to be replicated by a randomized clinical trial.
PMID- 26425100
TI - Combination of BCL-2 and MYC protein expression improves high-risk stratification
in diffuse large B-cell lymphoma.
AB - PURPOSE: To evaluate whether the addition of two biological markers (MYC and BCL
2 protein overexpression) improves the stratification of high-risk patients with
diffuse large B-cell lymphoma (DLBCL). METHOD: Seven risk factors were identified
at diagnosis, and a maximum of 7 points were assigned to each patient. The
patients were classified according to four risk groups: low (0-1), low
intermediate (2-3), high-intermediate (4), and high (5-7). Only high-risk
patients with DLBCL were included in this analysis. We retrospectively examined
20 cases from 2008 to 2013 at the Nanjing Drum Tower Hospital. RESULTS: The
median expression of MYC protein was 60%, and 17 of 20 (65%) evaluable cases
overexpressed MYC. The median expression of BCL-2 protein was also 60%. Eighteen
of 20 (90%) evaluable cases showed BCL-2 overexpression. Additionally, 12 out of
20 cases (60%) demonstrated coexpression of MYC and BCL-2 proteins. The
percentages of overall survival and progression-free survival at the median
follow-up time (36 months) were 33.3%+/-16.1% and 16.9%+/-13.5%, respectively. By
comparison, nine, four, and 20 patients were classified as high risk based on the
International Prognostic Index (IPI), National Comprehensive Cancer Network(NCCN)
IPI, and revised IPI criteria, respectively. According to the IPI and NCCN-IPI
stratification, the risk groups demonstrated closely overlapping survival curves.
In addition, four out of 20 cases were identified as low-intermediate risk
according to the NCCN-IPI criteria. CONCLUSION: The addition of MYC and BCL-2
protein expression to the IPI could identify a subset of DLBCL patients with high
risk clinicopathological characteristics and poor clinical outcome.
PMID- 26425101
TI - Diarrhea as initial manifestation of pulmonary artery intimal sarcoma: a case
report and literature review.
AB - Pulmonary artery intimal sarcoma (PAIS) is a rare malignant tumor that presents
with nonspecific symptoms and may be misdiagnosed as thromboembolic disease. We
report a case of a 40-year-old female who presented with diarrhea as the initial
symptom, was misdiagnosed and received thrombolytic therapy for presumed
pulmonary embolism. Progressive symptoms and subsequent surgery led to the
diagnosis of PAIS, and early relapse after pulmonary endarterectomy. Her survival
time was 17 months after pulmonary endarterectomy. To our knowledge, diarrhea as
initial manifestation of PAIS has not been described.
PMID- 26425102
TI - An exploratory retrospective assessment of a quantitative measure of diabetes
risk: medical management and patient impact in a primary care setting.
AB - BACKGROUND: Primary care providers with limited time and resources bear a heavy
responsibility for chronic disease prevention or progression. Reliable clinical
tools are needed to risk stratify patients for more targeted care. This
exploratory study examined the care of patients who had been risk stratified
regarding their likelihood of clinically progressing to type 2 diabetes. METHODS:
This was a retrospective chart review pilot study conducted to assess a primary
care provider's use of a risk screening test. In this quality improvement
project, the result of the risk screening was examined in relation to its
influence on medical management and clinical impact on patients at risk for
diabetes. All providers were board certified in family medicine and had more than
10 years clinical experience in managing diabetes and prediabetes. No specific
clinical practice guidelines were mandated for patient care in this pilot study.
Physicians in the practice group received an orientation to the diabetes risk
measure and its availability for use in a pilot study to be conducted over a 6
month period. We identified the 696 nondiabetic adults in family practices who
received a risk screening test (PreDx((r)), a multi-marker blood test that
estimates the 5-year likelihood of conversion to type 2 diabetes) between June
and November 2011 for a 6-month sample. A comparison group of 2,002 patients from
a total database of 3.2 million patients who did not receive the risk test was
randomly selected from the same clinical database after matching for age, sex,
selected diagnoses, and metabolic risk factors. Patient groups were compared for
intensity of care provided and clinical impact. RESULTS: Compared to patients
with a similar demographic and diagnostic profile, patients who had the risk test
received more intensive primary care and had better clinical outcome than
comparison patients. Risk-tested patients were more likely to return for follow
up visits, be monitored for relevant cardio-metabolic risk factors, and receive
prescription medications with P<0.001. Further, intensity of care was associated
with the level of risk test result: patients with moderate or high scores were
more likely to return for follow-up visits and receive prescription medications
than patients with low scores. All P-values for comparison patients between the
low and moderate groups, low and high groups, and moderate and high groups
resulted in P<0.001. Risk-tested patients were more likely than their comparison
group counterparts to achieve weight reduction, lowered blood pressure, and
improved blood glucose and cholesterol as demonstrated by P-values of <0.001.
CONCLUSION: Use of a risk stratification test in primary care may help providers
to more effectively identify high risk patients, manage diabetes risk, increase
patient involvement in diabetes risk management, and improve clinical outcomes. A
randomized controlled study is the next step to investigate the impact of
diabetes risk stratification in primary care.
PMID- 26425103
TI - Bariatric surgery outcomes: a single-center study in the United Arab Emirates.
AB - BACKGROUND: Bariatric surgery has become an attractive treatment for severe
obesity over the last decade, due to its impacts on weight loss and remission of
type 2 diabetes and metabolic syndrome. In the United Arab Emirates, a country
where the rate of obesity is dramatically increasing bariatric surgery has gained
popularity in recent years; however, published data on its outcomes in the
Emirati population are lacking. METHODS: We retrospectively reviewed the medical
records of 95 patients who underwent bariatric surgery (ie, laparoscopic Roux-en
Y gastric bypass [RYGB] or laparoscopic sleeve gastrectomy) at the Rashid Center
for Diabetes and Research in Ajman, United Arab Emirates. Weight outcomes and
metabolic marker data were abstracted at baseline and at 3, 6, and 12 months
postoperatively. RESULTS: Laparoscopic RYGB was the main procedure performed by
our bariatric unit. All variables demonstrated postoperative improvement. An
average excess weight loss of 68% was observed at 12 months. Fat mass was the
body component that decreased the most, with an average reduction of 46%.
Additionally, lipid profiles were significantly different (P<0.01) at 12 months,
with triglyceride levels improving by 27% and low-density lipoprotein levels
improving by 21%. Similarly, glycated hemoglobin (HbA1c) levels decreased
significantly (P<0.001) in patients with type 2 diabetes, with an average
reduction of 73%. CONCLUSION: Our results show that a substantial short-term
reduction in weight and significant improvements in metabolic markers followed
bariatric surgery in severely obese Emirati patients. Our results are consistent
with the outcomes of other internationally published studies. Additional studies
are warranted to determine whether the favorable impacts of bariatric surgery can
be sustained over the long term.
PMID- 26425104
TI - The clinical utility of aflibercept for diabetic macular edema.
AB - The treatment of center-involving diabetic macular edema (DME) has improved
because of the proven efficacy of drugs that inhibit the effects of vascular
endothelial growth factor (VEGF). The newest anti-VEGF drug, aflibercept, has
recently been approved by the United States Food and Drug Administration for the
treatment of center-involving DME and for diabetic retinopathy in eyes with DME.
In the pivotal Phase III VISTA and VIVID trials, intravitreal aflibercept 2 mg
injections every 4 or 8 weeks (after 5 monthly loading doses) produced superior
gains in BCVA compared to laser/sham injections. In the Diabetic Retinopathy
Clinical Research Network Protocol T trial, which featured monthly anti-VEGF
monotherapy for 6 months, followed by monthly pro re nata anti-VEGF injections
with laser rescue therapy from months 6 through 12, aflibercept 2 mg monthly was
superior to bevacizumab 1.25 mg and ranibizumab 0.5 mg in eyes with BCVA of 20/50
or worse (aflibercept versus bevacizumab: P<0.001; aflibercept versus
ranibizumab: P=0.003), but the three regimens were comparable for eyes with VA of
20/40 or better. Only in the 20/50 or worse subgroup did aflibercept achieve
clinical superiority (>5 letter difference) to bevacizumab. Each treatment
regimen led to significant macular thinning, with aflibercept being superior to
bevacizumab in both visual acuity subgroups (P<0.001 for each), but it was not
statistically superior to ranibizumab in either group. In diabetic patients,
aflibercept has an excellent safety profile that does not appear to differ from
laser/sham or other VEGF inhibitory drugs.
PMID- 26425106
TI - Atypical teratoid rhabdoid tumors: a population-based clinical outcomes study
involving 174 patients from the Surveillance, Epidemiology, and End Results
database (1973-2010).
AB - INTRODUCTION: Atypical teratoid rhabdoid tumors (ATRTs) are rare, highly
malignant embryonal tumors of the central nervous system (CNS) accounting for 20%
of CNS tumors in children under the age of 3. This study examines a large cohort
of ATRT patients to determine demographic, clinical, and pathologic factors which
impact prognosis and survival. METHODS: Demographic and clinical data were
abstracted on 174 ATRT patients (171 pediatric patients age <20 and 3 adult
patients age >=20) from the Surveillance, Epidemiology, and End Results database
(1973-2010). Standard statistical methodology was used. RESULTS: A total of 174
ATRT cases (mean age of 2.84 years) were identified. ATRT had a higher incidence
in males (56.3%), Caucasians (59.1%), and children <3 years of age (80.5%),
P<0.001. The most common primary sites were the cerebellum (17.8%), ventricles
(16.1%), and frontal lobe (12.6%). Mean overall survival was 3.2+/-0.4 years,
while overall and cancer-specific mortality were 63.2% and 56.3%, respectively,
P=0.005. Most ATRT cases were treated with surgery alone (58.0%), followed by a
combination of surgery and radiation (34.3%), no treatment (6.5%), and radiation
alone (1.2%). The use of combination therapy has increased significantly (16.1%)
since 2005 (P<0.001), while primary surgical resection and radiation therapy
rates remain relatively unchanged. The longest survival was observed among ATRT
patients receiving combination therapy (5.9+/-0.7 years), followed by radiation
alone (2.8+/-1.2 years), and surgery alone (1.9+/-0.4 years), P<0.001.
Multivariable analysis identified only distant metastases (OR =4.6) as
independently associated with increased mortality, whereas combination therapy
(OR =0.4) was associated with reduced mortality, P<0.005. CONCLUSION: ATRT is a
rare and highly aggressive embryonal malignancy of the CNS that presents more
often as locoregional tumors >4 cm in male Caucasian children of age <3 years,
involving the cerebellum, ventricles, or frontal lobe. Combination therapy
significantly improves survival, and its use has been increasing since 2005.
PMID- 26425107
TI - Relapsing polychondritis with different types of ocular inflammations.
AB - We were presented with two cases of relapsing polychondritis (RP) associated with
different types of ocular inflammation. The first case was a 35-year-old man who
had bilateral hyperemic conjunctiva and ocular pain, and was referred to Chiba
University Hospital with a diagnosis of episcleritis refractory. He was treated
with dexamethasone eye drops. He developed tinnitus, deafness in both ears, and
left auriculitis. A left auricular biopsy showed an infiltration of lymphocytes
surrounding the cartilage. He was diagnosed with RP and treated with 30 mg/day
oral prednisolone. After tapering the prednisolone, the scleritis in both eyes
improved. The second case was a 71-year-old man who was deaf in both ears and had
bilateral scleritis. At the first visit to our hospital, his left eyelid and
right auricula were reddish and swollen, and he reported some pain. He was
treated with intravenous antibiotics, and the left orbital cellulitis quickly
improved. However, he developed right scleritis and left gonitis. Magnetic
resonance imaging showed bilateral posterior scleritis and right auricular
perichondritis. Auricular biopsy showed an infiltration of lymphocytes into the
periauricular tissue. He was diagnosed with RP, and 40 mg/day oral prednisolone
was given and his symptoms improved. Although RP is rare, it is a life
threatening disease. Thus, ophthalmologists should consider RP in patients with
both ocular and auricular inflammation.
PMID- 26425108
TI - Optical coherence tomography imaging of chorioretinal folds associated with
hypotony maculopathy following pars plana vitrectomy.
AB - Chorioretinal folds may occur as a consequence of hypotony and can be a cause of
vision loss when associated with macular involvement. In this report, the
spectral domain ocular coherence tomography imaging of three patients with
chorioretinal folds before and after management are presented. The cases had
unique presentations and each underwent different management approaches, but the
results included improved visual acuities and lessened chorioretinal folds.
PMID- 26425105
TI - Genetics of inherited primary arrhythmia disorders.
AB - A sudden unexplained death is felt to be due to a primary arrhythmic disorder
when no structural heart disease is found on autopsy, and there is no preceding
documentation of heart disease. In these cases, death is presumed to be secondary
to a lethal and potentially heritable abnormality of cardiac ion channel
function. These channelopathies include congenital long QT syndrome,
catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and
short QT syndrome. In certain cases, genetic testing may have an important role
in supporting a diagnosis of a primary arrhythmia disorder, and can also provide
prognostic information, but by far the greatest strength of genetic testing lies
in the screening of family members, who may be at risk. The purpose of this
review is to describe the basic genetic and molecular pathophysiology of the
primary inherited arrhythmia disorders, and to outline a rational approach to
genetic testing, management, and family screening.
PMID- 26425109
TI - Evaluation of an automated single-channel sleep staging algorithm.
AB - BACKGROUND: We previously published the performance evaluation of an automated
electroencephalography (EEG)-based single-channel sleep-wake detection algorithm
called Z-ALG used by the Zmachine((r)) sleep monitoring system. The objective of
this paper is to evaluate the performance of a new algorithm called Z-PLUS, which
further differentiates sleep as detected by Z-ALG into Light Sleep, Deep Sleep,
and Rapid Eye Movement (REM) Sleep, against laboratory polysomnography (PSG)
using a consensus of expert visual scorers. METHODS: Single night, in-lab PSG
recordings from 99 subjects (52F/47M, 18-60 years, median age 32.7 years),
including both normal sleepers and those reporting a variety of sleep complaints
consistent with chronic insomnia, sleep apnea, and restless leg syndrome, as well
as those taking selective serotonin reuptake inhibitor/serotonin-norepinephrine
reuptake inhibitor antidepressant medications, previously evaluated using Z-ALG
were re-examined using Z-PLUS. EEG data collected from electrodes placed at the
differential-mastoids (A1-A2) were processed by Z-ALG to determine wake and
sleep, then those epochs detected as sleep were further processed by Z-PLUS to
differentiate into Light Sleep, Deep Sleep, and REM. EEG data were visually
scored by multiple certified polysomnographic technologists according to the
Rechtschaffen and Kales criterion, and then combined using a majority-voting rule
to create a PSG Consensus score file for each of the 99 subjects. Z-PLUS output
was compared to the PSG Consensus score files for both epoch-by-epoch (eg,
sensitivity, specificity, and kappa) and sleep stage-related statistics (eg,
Latency to Deep Sleep, Latency to REM, Total Deep Sleep, and Total REM). RESULTS:
Sensitivities of Z-PLUS compared to the PSG Consensus were 0.84 for Light Sleep,
0.74 for Deep Sleep, and 0.72 for REM. Similarly, positive predictive values were
0.85 for Light Sleep, 0.78 for Deep Sleep, and 0.73 for REM. Overall, kappa
agreement of 0.72 is indicative of substantial agreement. CONCLUSION: This study
demonstrates that Z-PLUS can automatically assess sleep stage using a single A1
A2 EEG channel when compared to the sleep stage scoring by a consensus of
polysomnographic technologists. Our findings suggest that Z-PLUS may be used in
conjunction with Z-ALG for single-channel EEG-based sleep staging.
PMID- 26425110
TI - Rate and predictors of low serum ferritin levels among healthy parturient women
in Enugu, Nigeria.
AB - BACKGROUND: Low serum ferritin levels signify low iron stores and this could
predispose to iron deficiency anemia. OBJECTIVE: To determine the rate and
predictors of low serum ferritin levels during the puerperium in Enugu, Southeast
Nigeria. STUDY DESIGN: A hospital-based prospective longitudinal study involving
parturient women who delivered singleton fetuses at term. Venous blood samples
were collected to determine the serum ferritin concentration at 48 hours and 6
weeks postpartum. Data analysis involved descriptive and inferential statistics
at 95% confidence interval (CI) using Statistical Package for Social Sciences
(SPSS) computer software version 20.0. RESULTS: Two-hundred and two women who
carried singleton pregnancies to term were studied. The mean serum ferritin
levels at 48 hours and 6 weeks were 27.82+/-18.41 ug/L and 36.12+/-21.53 ug/L,
respectively. Forty-eight hours postdelivery, 29.2% had low ferritin levels and
this decreased to 12.4% at 6 weeks postpartum. There was a significant positive
correlation between the serum ferritin level at 48 hours postdelivery and the
serum ferritin level at 6 weeks postpartum (r=0.89, P<0.001). Predictors of the
low ferritin level at 6 weeks included age <20 years (odds ratio [OR] =0.70, 95%
CI =0.53, 0.93), multiparity (OR =63.7, 95% CI =3.18, 127.5), anemia at 48 hours
postpartum (OR =61.7, 95% CI =13.27, 116.6), a low ferritin level at 48 hours (OR
=78.1, 95% CI =8.8, 108.3), and intake of antenatal hematinics for <3 months (OR
=0.04, 95% CI =0.01, 0.20). CONCLUSION: There was a significant occurrence of low
ferritin levels during the puerperium in the study centers, and this was
associated mainly with pregnancy and delivery factors. Efforts to improve the
iron stores in parturient women could benefit from early booking and compliance
with antenatal hematinics and optimizing hemoglobin and iron levels before
delivery.
PMID- 26425112
TI - Beverage- and Brand-Specific Binge Alcohol Consumption among Underage Youth in
the U.S.
AB - BACKGROUND AND OBJECTIVES: Binge drinking is a common and risky pattern of
alcohol consumption among youth; beverage and brand-specific consumption during
binge drinking is poorly understood. The objective was to characterize beverage-
and brand-specific consumption associated with binge drinking among underage
youth in the U.S. METHODS: An internet panel was used to obtain a sample of 1,032
underage youth aged 13-20, who drank alcohol in the past 30 days. For each brand
consumed, youth reported drinking quantity and frequency, and whether they
engaged in binge drinking with that brand (>=5 drinks for males, >=4 for
females). Each youth reporting binge drinking with a brand constituted a binge
drinking report. RESULTS: Overall, 50.9% of youth binge drank with >=1 brand, and
36.5% of youth who consumed any particular brand reported binge drinking with it.
Spirits accounted for 43.8% of binge drinking reports. Twenty-five brands
accounted for 46.2% of binge drinking reports. Many of these brands were
disproportionately associated with binge drinking relative to their youth market
share. CONCLUSIONS: Binge drinking among youth is most commonly involves spirits,
and binge drinking is concentrated within a relatively small number of brands.
Understanding factors underlying beverage and brand preference among binge
drinking youth could assist prevention efforts.
PMID- 26425111
TI - Cadmium induces apoptosis in primary rat osteoblasts through caspase and mitogen
activated protein kinase pathways.
AB - Exposure to cadmium (Cd) induces apoptosis in osteoblasts (OBs); however, little
information is available regarding the specific mechanisms of Cd-induced primary
rat OB apoptosis. In this study, Cd reduced cell viability, damaged cell
membranes and induced apoptosis in OBs. We observed decreased mitochondrial
transmembrane potentials, ultrastructure collapse, enhanced caspase-3 activity,
and increased concentrations of cleaved PARP, cleaved caspase-9 and cleaved
caspase-3 following Cd treatment. Cd also increased the phosphorylation of p38
mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases
(ERK)1/2 and c-jun N-terminal kinase (JNK) in OBs. Pretreatment with the caspase
inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, ERK1/2 inhibitor
(U0126), p38 inhibitor (SB203580) and JNK inhibitor (SP600125) abrogated Cd
induced cell apoptosis. Furthermore, Cd-treated OBs exhibited signs of oxidative
stress protection, including increased antioxidant enzymes superoxide dismutase
and glutathione reductase levels and decreased formation of reactive oxygen
species. Taken together, the results of our study clarified that Cd has direct
cytotoxic effects on OBs, which are mediated by caspase- and MAPK pathways in Cd
induced apoptosis of OBs.
PMID- 26425113
TI - A study protocol for a cluster randomised trial for the prevention of chronic
suppurative otitis media in children in Jumla, Nepal.
AB - BACKGROUND: Chronic Suppurative Otitis Media (CSOM) is the commonest cause of
preventable deafness, affecting 164 million people worldwide, 90 % of whom live
in low resource countries, such as Nepal. Simple, inexpensive treatment of acute
otitis media can prevent the development of CSOM and its sequelae: deafness,
abscess, encephalitis, and, rarely, death. CSOM is a disease of poverty and its
social determinants: low parental education, overcrowding, poor hygiene and
malnutrition. Previous studies have established economic, socio-cultural and
geographic barriers to care seeking for childhood illness in the developing world
and, in particular, in Nepal. The ultimate aim of this research is to improve the
ear health of the children in Jumla, Nepal. The primary outcome is an increase in
mother's knowledge, attitude and practice regarding ear disease in their
children. The secondary outcome is a reduction in the prevalence of CSOM in their
children. METHODS/DESIGN: Using 56 existing women's self-help groups, sample
size, adjusting for clustering and data analysis, is set at 15 groups per arm. A
baseline survey of 30 randomly selected groups will be performed, consisting of a
knowledge, attitude and practice questionnaire aimed at women who participate in
self-help groups, as well as examination of their children's ears. This will be
followed by random allocation, stratified by geography, into 15 intervention and
15 control groups. The intervention groups will participate in three interactive
educational sessions at their regular monthly meetings based on World Health
Organisation Primary Ear and Hearing Resource, Basic Level. The control groups
will continue their usual monthly group meetings. At 12 months, a follow-up
assessment of both control and intervention groups will be performed, with a
repeat women's survey and repeat ear examination of the children. Data analysis
will be by intention to treat and clustering will be considered at every stage.
Cluster level data will be analysed using t-test and individual level data using
mixed effects linear regression and logistic regression random effects model as
appropriate. DISCUSSION: Despite its remote location, Jumla has a vibrant network
of health posts and community workers. This project uses existing, local
resources and will be undertaken in a way that is consistent with the cultural
understanding of the local community in Jumla and acceptable to local care
givers. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register,
ACTRN12614000231640.
PMID- 26425115
TI - Losing trust in the world: Humiliation and its consequences.
AB - The author identifies acts of humiliation as a specific and often traumatic way
of exercising power, with a set of consistently occurring elements and
predictable consequences, including a loss of the ability to trust others. It is
argued that these consequences are serious and long-lasting. The article makes a
distinction between 'shame' as a state of mind and 'humiliation' as an act
perpetrated against a person or group. The interplay between humiliation and
shame after a humiliating act is discussed. It is argued that the patient's
recovery of the capacity to resume a relatively normal life is made more likely
if the therapist acknowledges the specificity of humiliation, the impossibility
of reversing a humiliating act and the importance of focussing on the
consequences of humiliation.
PMID- 26425114
TI - Implications of miR cluster 143/145 as universal anti-oncomiRs and their
dysregulation during tumorigenesis.
AB - Tumorigenesis is a multistep process, de-regulated due to the imbalance of
oncogenes as well as anti-oncogenes, resulting in disruption of tissue
homeostasis. In many cases the effect of oncogenes and anti-oncogenes are
mediated by various other molecules such as microRNAs. microRNAs are small non
coding RNAs established to post-transcriptionally regulate more than half of the
protein coding genes. miR cluster 143/145 is one such cancer-related microRNA
cluster which is down-regulated in most of the cancers and is able to hinder
tumorigenesis by targeting tumor-associated genes. The fact that they could
sensitize drug-resistant cancer cells by targeting multidrug resistant genes
makes them potent tools to target cancer cells. Their low levels precede events
which lead to cancer progression and therefore could be considered also as
biomarkers to stage the disease. Interestingly, evidence suggests the existence
of several in vivo mechanisms by which this cluster is differentially regulated
at the molecular level to keep their levels low in cancer. In this review, we
summarize the roles of miR cluster 143/145 in cancer, their potential prognostic
applications and also their regulation during tumorigenesis.
PMID- 26425117
TI - The importance of regional availability of health care for old age survival -
Findings from German reunification.
AB - BACKGROUND: This article investigates the importance of regional health care
availability for old age survival. Using German reunification as a natural
experiment, we show that spatial variation in health care in East Germany
considerably influenced the convergence of East German life expectancy toward
West German levels. METHOD: We apply cause-deleted life tables and continuous
mortality decomposition for the years 1982-2007 to show how reductions in
circulatory mortality among the elderly affected the East German catch-up in life
expectancy. RESULTS: Improvements in remaining life expectancy at older ages were
first seen in towns with university hospitals, where state-of-the-art services
became available first. CONCLUSION: Our results suggest that the modernization of
the health care system had a substantial effect on old-age life expectancy and
helped to significantly reduce circulatory diseases as the main cause of death in
East Germany.
PMID- 26425116
TI - Effects of exercise on brain and peripheral inflammatory biomarkers induced by
total sleep deprivation in rats.
AB - BACKGROUND: Physical exercise induces neuroprotection through anti-inflammatory
effects and total sleep deprivation is reported an inflammatory process. We
examined whether 7 weeks of exercise training attenuates markers of inflammation
during total sleep deprivation (24-h wakefulness) in the rat brain and periphery.
METHODS: Four groups of 10 rats were investigated: Sedentary control, Sedentary
sleep-deprived, Exercised control, and Exercised sleep-deprived. Sleep
deprivation and exercise training were induced using slowly rotating wheels and a
motorized treadmill. We examined mRNA expression of pro-inflammatory (IL-1beta,
TNF-alpha, and IL-6) cytokine-related genes using real-time PCR, and protein
levels in the hippocampus and frontal cortex, as well as circulating
concentrations. RESULTS: Compared to Sedentary control rats, hippocampal and
cortical IL-1beta mRNA expressions in Sedentary sleep-deprived rats were up
regulated (p < 0.05 and p < 0.01 respectively). At the protein level, hippocampal
IL-1beta and TNF-alpha and cortical IL-6 contents were higher in Sedentary sleep
deprived rats (p < 0.001, p < 0.05, p < 0.05, respectively). Peripherally, TNF
alpha, IL-6 and norepinephrine concentrations were higher in Sedentary sleep
deprived rats compared to Sedentary control (p < 0.01, p < 0.001, p < 0.01,
respectively). Exercise training reduced the sleep deprivation-induced
hippocampal IL-1beta increases (mRNA expression and protein content) (p < 0.05
and p < 0.001), and TNF-alpha content (p < 0.001). At the periphery, exercise
reduced sleep deprivation-induced increase of IL-6 concentration (p < 0.05)
without effect on TNF-alpha and norepinephrine. CONCLUSIONS: We demonstrate that
a 7-week exercise training program before acute total sleep deprivation prevents
pro-inflammatory responses in the rat hippocampus, particularly the IL-1beta
cytokine at the gene expression level and protein content.
PMID- 26425118
TI - American trypanosomiasis and associated risk factors in owned dogs from the major
city of Yucatan, Mexico.
AB - BACKGROUND: The American trypanosomiasis is a zoonosis caused by the protozoa
Trypanosoma cruzi (T. cruzi). The disease is widely distributed throughout the
American continent, affecting a wide range of hosts, including dogs. It is
present in the canine population in the State of Yucatan, Mexico. However, no
significant studies in owned dogs have been performed in the metropolitan area of
Merida. A transversal study was conducted in 370 owned dogs from Merida, Yucatan,
Mexico. METHODS: A cross-sectional study including 370 dogs was performed in a
major city of Yucatan, Mexico, to detect IgG antibodies against T. cruzi. A
commercial ELISA test kit was used and a chi-square test used to evaluate
associated risk factors; odds ratio (OR) and 95 % confidence interval (CI) were
also estimated. RESULTS: The indirect ELISA and western blot (WB) tests were used
to detect specific immunoglobulin G antibodies against T. cruzi in serum samples.
A prevalence of 12.2 % was found; age and area of residence were statistically
associated with seropositivity in dogs (p <0.05). CONCLUSIONS: Results from the
present study suggests the presence and abundance of the vector in urban
conditions where a high number of seropositive cases of T. cruzi cases were
found.
PMID- 26425119
TI - Sun Protection Behaviors Associated with Self-Efficacy, Susceptibility, and
Awareness among Uninsured Primary Care Patients Utilizing a Free Clinic.
AB - Background. Skin cancer is the most commonly diagnosed form of cancer in the
United States (US). However, knowledge, behaviors, and attitudes regarding sun
protection vary among the general population. The purpose of this study is to
examine sun protection behaviors of low-income primary care patients and assess
the association between these health behaviors and the self-efficacy,
susceptibility, and skin cancer awareness. Methods. Uninsured primary care
patients utilizing a free clinic (N = 551) completed a self-administered survey
in May and June 2015. Results. Using sunscreen was the least common tactic among
the participants of this study. Skin cancer awareness and self-efficacy are
important to improve sun protection behaviors. Spanish speakers may have lower
levels of skin care awareness compared to US born and non-US born English
speakers. Male and female participants use different sun protection methods.
Conclusion. It is important to increase skin cancer awareness with self-efficacy
interventions as well as education on low-cost sun protection methods. Spanish
speaking patients would be a target population for promoting awareness. Male and
female patients would need separate gender-specific sun protection education.
Future studies should implement educational programs and assess the effectiveness
of the programs to further promote skin cancer prevention among underserved
populations.
PMID- 26425120
TI - Dissecting the Potential Interplay of DEK Functions in Inflammation and Cancer.
AB - There is a long-standing correlation between inflammation, inflammatory cell
signaling pathways, and tumor formation. Understanding the mechanisms behind
inflammation-driven tumorigenesis is of great research and clinical importance.
Although not entirely understood, these mechanisms include a complex interaction
between the immune system and the damaged epithelium that is mediated by an array
of molecular signals of inflammation-including reactive oxygen species (ROS),
cytokines, and NFkappaB signaling-that are also oncogenic. Here, we discuss the
association of the unique DEK protein with these processes. Specifically, we
address the role of DEK in chronic inflammation via viral infections and
autoimmune diseases, the overexpression and oncogenic activity of DEK in cancers,
and DEK-mediated regulation of NFkappaB signaling. Combined, evidence suggests
that DEK may play a complex, multidimensional role in chronic inflammation and
subsequent tumorigenesis.
PMID- 26425121
TI - Pulmonary Venous Obstruction in Cancer Patients.
AB - Background. We study the clinical significance and management of pulmonary venous
obstruction in cancer patients. Methods. We conducted a prospective cohort study
to characterize the syndrome that we term "pulmonary vein obstruction syndrome"
(PVOS) between January 2005 and March 2014. The criteria for inclusion were (1)
episodes of shortness of breath; (2) chest X-ray showing abnormal pulmonary hilum
shadow with or without presence of pulmonary edema and/or pleural effusion; (3)
CT scan demonstrating pulmonary vein thrombosis/tumor with or without tumor
around the vein. Results. Two hundred and twenty-two patients developed PVOS.
Shortness of breath was the main symptom, which was aggravated by chemotherapy in
28 (13%), and medical/surgical procedures in 21 (9%) and showed diurnal change in
intensity in 32 (14%). Chest X-rays all revealed abnormal pulmonary hilum shadows
and presence of pulmonary edema in 194 (87%) and pleural effusion in 192 (86%).
CT scans all showed pulmonary vein thrombosis/tumor (100%) and surrounding the
pulmonary veins by tumor lesions in 140 patients (63%). PVOS was treated with low
molecular weight heparin in combination with dexamethasone, and 66% of patients
got clinical/image improvement. Conclusion. Physicians should be alert to PVOS
when shortness of breath occurs and chest X-ray reveals abnormal pulmonary hilum
shadows.
PMID- 26425122
TI - Epithelial to Mesenchymal Transition in a Clinical Perspective.
AB - Tumor growth and metastatic dissemination rely on cellular plasticity. Among the
different phenotypes acquired by cancer cells, epithelial to mesenchymal
transition (EMT) has been extensively illustrated. Indeed, this transition allows
an epithelial polarized cell to acquire a more mesenchymal phenotype with
increased mobility and invasiveness. The role of EMT is quite clear during
developmental stage. In the neoplastic context in many tumors EMT has been
associated with a more aggressive tumor phenotype including local invasion and
distant metastasis. EMT allows the cell to invade surrounding tissues and survive
in the general circulation and through a stem cell phenotype grown in the host
organ. The molecular pathways underlying EMT have also been clearly defined and
their description is beyond the scope of this review. Here we will summarize and
analyze the attempts made to block EMT in the therapeutic context. Indeed, till
today, most of the studies are made in animal models. Few clinical trials are
ongoing with no obvious benefits of EMT inhibitors yet. We point out the
limitations of EMT targeting such tumor heterogeneity or the dynamics of EMT
during disease progression.
PMID- 26425124
TI - Frequency of Red Cell Alloimmunization and Autoimmunization in Thalassemia
Patients: A Report from Eastern India.
AB - Introduction. Red blood cell (RBC) alloimmunization and autoimmunization remain a
major problem in transfusion dependent thalassemic patients. There is a paucity
of data on the incidence of RBC alloimmunization and autoimmunization in
thalassemic patients from eastern part of India, as pretransfusion antibody
screening is not routinely performed. Aims. To assess the incidence of RBC
alloimmunization and autoimmunization in transfusion dependent thalassemic
patients in eastern India. Materials and Methods. Total 500 thalassemia cases
were evaluated. The antibody screening and identification were performed with
commercially available panel cells (Diapanel, Bio-rad, Switzerland) by column
agglutination method. To detect autoantibodies, autocontrol and direct
antiglobulin tests were carried out using polyspecific coombs (IgG + C3d) gel
cards in all patients. Results. A total of 28 patients developed RBC
alloimmunization (5.6%) and 5 patients had autoantibodies (1%). Alloantibody
against c had the highest incidence (28.57%) followed by E (21.42%). Five out of
28 (17.85%) patients had developed antibodies against both c and E. Conclusion.
Data from this study demonstrate that the RBC alloantibody and autoantibody
development rates are significant in our region. Thus, pretransfusion antibody
screening needs to be initiated in eastern India in order to ensure safe
transfusion practice.
PMID- 26425123
TI - Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response
Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study.
AB - Background. In a French large population-based case-control study we investigated
the dose-response relationship between lung cancer and occupational exposure to
diesel motor exhaust (DME), taking into account asbestos exposure. Methods.
Exposure to DME was assessed by questionnaire. Asbestos was taken into account
through a global indicator of exposure to occupational carcinogens or by a
specific JEM. Results. We found a crude dose response relationship with most of
the indicators of DME exposure, including with the cumulative exposure index. All
results were affected by adjustment for asbestos exposure. The dose response
relationships between DME and lung cancer were observed among subjects never
exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently
found among the same subjects, which may explain why dose-response relationships
in previous studies that adjusted for asbestos exposure were inconsistent.
PMID- 26425125
TI - The Association of Polymorphisms in Leptin/Leptin Receptor Genes and
Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic
Disturbances: A Review.
AB - CONTEXT: Leptin and ghrelin are two important appetite and energy balance
regulating peptides. Common polymorphisms in the genes coding these peptides and
their related receptors are shown to be associated with body weight, different
markers of obesity and metabolic abnormalities. This review article aims to
investigate the association of common polymorphisms of these genes with
overweight/obesity and the metabolic disturbances related to it. EVIDENCE
ACQUISITION: The keywords leptin, ghrelin, polymorphism, single-nucleotide
polymorphism (SNP), obesity, overweight, Body Mass Index, metabolic syndrome, and
type 2 diabetes mellitus (T2DM) (MeSH headings) were used to search in the
following databases: Pubmed, Sciencedirect (Elsevier), and Google scholar.
Overall, 24 case-control studies, relevant to our topic, met the criteria and
were included in the review. RESULTS: The most prevalent leptin/leptin receptor
genes (LEP/LEPR) and ghrelin/ghrelin receptor genes (GHRL/GHSR) single nucleotide
polymorphisms studied were LEP G-2548A, LEPR Q223R, and Leu72Met, respectively.
Nine studies of the 17 studies on LEP/LEPR, and three studies of the seven
studies on GHRL/GHSR showed significant relationships. CONCLUSIONS: In general,
our study suggests that the association between LEP/LEPR and GHRL/GHSR with
overweight/obesity and the related metabolic disturbances is inconclusive. These
results may be due to unidentified gene-environment interactions. More
investigations are needed to further clarify this association.
PMID- 26425126
TI - The Association of Dairy Intake With Metabolic Syndrome and Its Components in
Adolescents: Tehran Lipid and Glucose Study.
AB - BACKGROUND: Epidemiological studies have shown that consumption of dairy product
plays an important role in prevention and treatment of Metabolic Syndrome (MetS).
OBJECTIVES: The objective of this study was to examine the association of dairy
intake with MetS and its components in Tehranian adolescents. PATIENTS AND
METHODS: In this cross-sectional study, 785 adolescent aged 10 to 19 years,
participated from the fourth phase of the Tehran Lipid and Glucose Study. Usual
dietary intake was assessed using a valid semi quantitative food frequency
questionnaire. Total dairy, low fat and high fat dairy, milk, yoghurt and cheese
were evaluated. Assessment of anthropometric, biochemical and blood pressure was
performed and MetS was defined according to the de Ferranti criteria. RESULTS:
The mean age of subjects was 14.8 +/- 2.9 years. The prevalence of MetS was 22.2%
(girls: 19.5% and boys: 25.2%). The most prevalent risk factor for MetS in boys
was high waist circumference (53.4%) and among girls was low HDL-C (53.1%).
Energy density and intake of protein, total fat, saturated fat, cholesterol,
calcium and phosphor were higher in the highest quartile of dairy consumption
than the lowest quartile. After adjustments for confounders, odds ratios with 95%
confidence interval for MetS in the highest quartile of total dairy, low fat
dairy, high fat dairy, milk, yoghurt and cheese compared with lowest quartile
were respectively 0.97 (0.57 - 1.66), 1.44 (0.83 - 2.49), 0.97 (0.56 - 1.67),
0.70 (0.42 - 1.18), 1.62 (0.99 - 2.64) and 0.72 (0.44 - 1.18). CONCLUSIONS:
Results of this study did not support the hypothesis that dairy products
consumption protects against MetS and its components.
PMID- 26425127
TI - A Longitudinal Study of Adherence to the Mediterranean Dietary Pattern and
Metabolic Syndrome in a Non-Mediterranean Population.
AB - BACKGROUND: Adherence to the Mediterranean diet (MedDiet) has been proposed to
reduce the risk of metabolic syndrome (MetS), but the association of the diet on
MetS in non-Mediterranean populations remains unclear. OBJECTIVES: The aim of
this study was to investigate whether adherence to the MedDiet is related to the
incident MetS and its components during a 3-year follow-up among Iranian adults.
PATIENTS AND METHODS: Longitudinal associations between the MedDiet and MetS
components were investigated on 2241 adults, aged 18 - 74 years, without type 2
diabetes selected from participants of the Tehran lipid and glucose study (TLGS).
The association between the MedDiet and MetS incidence was also examined in 1661
participants, free of Mets at baseline. Adherence to the MedDiet was assessed
using the traditional Mediterranean diet score (MDS) and a recently posteriori
adaptation of the MDS of Sofi et al. (Sofi-MDS). MetS was defined according to
the recent interim consensus. RESULTS: After adjusting for potential confounders,
neither higher MDS nor higher Sofi-MDS were significantly associated with the
mean values of MetS components and the risk of metabolic abnormalities incidence
after 3 years follow-up. During the 3 years of follow-up, 246 developed MetS were
identified. In multivariable model, the adjusted odds ratio (OR) of developing
MetS did not differ significantly in participants with the highest tertile of the
MDS (OR (95% CI): 0.88 (0.62 - 1.23)) or sofi-MDS (OR (95% CI):1.12 (0.77 -
1.62)) compared to those in the lowest tertiles. CONCLUSIONS: Adherence to the
MedDiet, according to MDS and Sofi-MDS, may not predict MetS components and MetS
incidence after 3 years of follow-up in Iranian adult populations.
PMID- 26425128
TI - Development of an In-House TaqMan Real Time RT-PCR Assay to Quantify Hepatitis C
Virus RNA in Serum and Peripheral Blood Mononuclear Cells in Patients With
Chronic Hepatitis C Virus Infection.
AB - BACKGROUND: Viral load measurements are commonly used to monitor HCV infection in
patients with chronic diseases or determining the number of HCV-genomes in serum
samples of patients after sustained virological response. However, in some
patients, HCV viral load in serum samples is too low to be detected by PCR,
especially after treatment. OBJECTIVES: The aim of this study was to develop a
highly specific, sensitive, and reproducible in-house quantitative PCR using
specific primers and probe cited in highly conservative region of HCV genome that
allows simultaneous detection of HCV genotypes 1 - 4. MATERIALS AND METHODS: In
this study, three sets of primer pairs and a TaqMan probe for amplification and
detection of selected region within 5'-non-coding (5'NCR) of four HCV genotypes
were used. Using plasmid containing 5'NCR region of HCV, standard curve,
threshold, and threshold cycle (CT) values were determined. Real-time and nested
PCR were performed on HCV genotypes 1 - 4 extracted from plasma and peripheral
blood mononuclear cells (PBMCs) samples collected from patients with chronic HCV
infection. RESULTS: The lower limit detection of this in-house HCV real-time RT
PCR was determined as 100 RNA copies/mL. Inter- and intra-assay coefficient of
variation (CV) of this in-house HCV real-time RT-PCR ranged from 0.9% to 1.8% and
1.76% to 3.94%, respectively. The viral load of the genotyped samples ranged from
2.0 * 10(6) +/- 0.31 to 2.7 * 10(5) +/- 0.46 copies/mL in serum samples and 5 *
10(2) +/- 0.36 to 4.0 * 10(3) +/- 0.51 copies/10(6) cells/mL of PBMCs.
CONCLUSIONS: The quite sensitive in-house TaqMan real time RT-PCR assay was able
to detect and quantify all four main HCV genotypes prevailing around all
geographical regions of Iran.
PMID- 26425129
TI - Tocotrienol-Rich Fraction from Rice Bran Demonstrates Potent Radiation Protection
Activity.
AB - The vitamin E analogs delta-tocotrienol (DT3) and gamma-tocotrienol (GT3) have
significant protective and mitigative capacity against the detrimental effects of
ionizing radiation (IR). However, the expense of purification limits their
potential use. This study examined the tocotrienol-rich fraction of rice bran
(TRFRB) isolated from rice bran deodorizer distillate, a rice oil refinement
waste product, to determine its protective effects against IR induced oxidative
damage and H2O2. Several cell lines were treated with tocotrienols or TRFRB prior
to or following exposure to H2O2 or IR. To determine the radioprotective capacity
cells were analyzed for morphology, mitochondrial bioenergetics, clonogenic
survival, glutathione oxidation, cell cycle, and migration rate. TRFRB displayed
similar antioxidant activity compared to pure tocotrienols. Cells pretreated with
TRFRB or DT3 exhibited preserved cell morphology and mitochondrial respiration
when exposed to H2O2. Oxidized glutathione was decreased in TRFRB treated cells
exposed to IR. TRFRB reversed mitochondrial uncoupling and protected cells
migration rates following IR exposure. The protective antioxidant capacity of
TRFRB treated cells against oxidative injury was similar to that of purified DT3.
TRFRB effectively protects normal cells against IR induced injury suggesting that
rice bran distillate may be an inexpensive and abundant alternate source.
PMID- 26425130
TI - The Efficacy of Acupuncture for the Treatment of Sciatica: A Systematic Review
and Meta-Analysis.
AB - Background. Sciatica is one of the most frequently reported complaints; it
affects quality of life and reduces social and economic efficacy. Clinical
studies on the efficacy of acupuncture therapy in sciatica are increasing, while
systematic reviews assessing the efficacy of acupuncture therapy are still
lacking. Objective. This study aims to assess the effectiveness of acupuncture
therapy for sciatica. Methods. Comprehensive searches of 8 databases were
conducted up until April 2015. Outcomes included effectiveness (proportion of
patients who improved totally or partly in clinical symptoms), pain intensity,
and pain threshold. Effect sizes were presented as risk ratio (RR) and mean
difference (MD). Pooled effect sizes were calculated by fixed effects or random
effects model. Results. A total of 12 studies (involving 1842 participants) were
included. Results showed that acupuncture was more effective than conventional
Western medicine (CWM) in outcomes effectiveness (RR 1.21, 95% CI: 1.16-1.25),
pain intensity (MD -1.25, 95% CI: -1.63 to -0.86), and pain threshold (MD: 1.08,
95% CI: 0.98-1.17). Subgroup and sensitivity analysis found that the results did
not change in different treatment method and drug categories substantially. The
reported adverse effects were acceptable. Conclusions. Acupuncture may be
effective in treating the pain associated with sciatica.
PMID- 26425131
TI - Anti-Inflammatory Effects of Cumin Essential Oil by Blocking JNK, ERK, and NF
kappaB Signaling Pathways in LPS-Stimulated RAW 264.7 Cells.
AB - Cumin seeds (Cuminum cyminum L.) have been commonly used in food flavoring and
perfumery. In this study, cumin essential oil (CuEO) extracted from seeds was
employed to investigate the anti-inflammatory effects in lipopolysaccharide- (LPS
) stimulated RAW 264.7 cells and the underlying mechanisms. A total of 26
volatile constituents were identified in CuEO by GC-MS, and the most abundant
constituent was cuminaldehyde (48.773%). Mitochondrial-respiration-dependent 3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction assay
demonstrated that CuEO did not exhibit any cytotoxic effect at the employed
concentrations (0.0005-0.01%). Real-time PCR tests showed that CuEO significantly
inhibited the mRNA expressions of inducible nitric oxide synthase (iNOS),
cyclooxygenase (COX-2), interleukin- (IL-) 1, and IL-6. Moreover, western
blotting analysis revealed that CuEO blocked LPS-induced transcriptional
activation of nuclear factor-kappa B (NF-kappaB) and inhibited the
phosphorylation of extracellular signal regulated kinase (ERK) and c-Jun N
terminal kinase (JNK). These results suggested that CuEO exerted anti
inflammatory effects in LPS-stimulated RAW 264.7 cells via inhibition of NF
kappaB and mitogen-activated protein kinases ERK and JNK signaling; the chemical
could be used as a source of anti-inflammatory agents as well as dietary
complement for health promotion.
PMID- 26425132
TI - Erratum to: The effect of aging on the frequency, phenotype and cytokine
production of human blood CD4 + CXCR5 + T follicular helper cells: comparison of
aged and young subjects.
AB - [This corrects the article DOI: 10.1186/1742-4933-11-12.].
PMID- 26425133
TI - Development of cryptococcal immune reconstitution inflammatory syndrome 41 months
after the initiation of antiretroviral therapy in an AIDS patient.
AB - Cryptococcal meningitis is one of the most lethal fungal infections in patients
with acquired immune deficiency syndrome (AIDS). The incidence of and mortality
from cryptococcal meningitis have markedly decreased since the introduction of
combination antiretroviral therapy (cART). However, despite its benefits, the
initiation of cART results in immune reconstitution inflammatory syndrome (IRIS)
in some patients. Although IRIS is occasionally difficult to distinguish from
relapse or treatment failure, the distinction is important because IRIS requires
a different treatment. Here, we present the case of a patient with AIDS who
developed symptoms of cryptococcal IRIS 41 months after starting cART. To the
best of our knowledge, the time between cART initiation and the onset of
cryptococcal IRIS in this patient is the longest that has been reported in the
literature.
PMID- 26425134
TI - Is DOG1 really useful in the diagnosis of salivary gland acinic cell carcinoma? -
A DOG1 (clone K9) analysis in fine needle aspiration cell blocks and the review
of the literature.
AB - INTRODUCTION: DOG1 is a transmembrane protein originally "discovered on
gastrointestinal stromal tumors," works as a calcium-activated chloride channel
protein. There is a limited number of studies on the potential usage of this
antibody in the diagnosis of salivary gland tumors on routine practice in cell
blocks. The aim of this study was to search for the usefulness of K9 clone in
oncocytic type tumors and review of the literature. MATERIALS AND METHODS: Sixty
nine fine needle aspiration (FNA) cytologic materials of predominantly oncocytic
morphology salivary gland tumors; acinic cell carcinoma (AciCC) (n = 8), adenoid
cystic carcinoma (n = 2), pleomorphic adenoma (PA) (n = 22), Warthin tumor (WT)
(n = 20), myoepithelioma (ME) (n = 5), benign oncocytoma (BeO) (n = 3),
mucoepidermoid carcinoma (MEC) (n = 7), mammary analog salivary gland carcinoma
(n = 2) were immunostained with DOG1 (clone K9) stain. RESULTS: Of the 8 AciCCs,
7 were observed apical-luminal positive staining, demonstrating 1-3 + intensity,
and involving 40-70% of the tumor cells. One MEC of 7 (14%), 1 ME of 5 (20%), and
4 PA of 22 (18%) showed weak (1+) cytoplasmic granular staining in 5-10% of the
tumor cells. Pure oncocytic neoplasms (WT, BeO) showed no expression with DOG1
K9. CONCLUSIONS: FNA is a common tool in the diagnosis and management of salivary
gland tumors. DOG1-K9 clone was very useful with a unique staining pattern of
apical-luminal positivity in the differential diagnosis of AciCC from other
oncocytic salivary gland tumors.
PMID- 26425135
TI - Merkel cell carcinoma presenting as malignant ascites: A case report and review
of literature.
AB - The most common site of metastasis to ascitic fluid in females is from a
mullerian (ovarian) primary, whereas in males it is from the gastrointestinal
tract. Metastatic Merkel cell carcinoma (MCC) to the ascitic fluid is extremely
rare and may present as a diagnostic challenge on effusion cytology. In a review
of the literature, there are only two case reports of metastatic MCC in pleural
effusion. To the best of our knowledge, we present the first cytological
diagnosis of MCC metastatic to the ascitic fluid. We describe the cytologic
findings as well as the immunohistochemical stains supportive of the diagnosis.
Given the fatal prognosis of this tumor compared to melanoma and rarity of its
occurrence in ascitic fluid, awareness of this tumor and use of
immunohistochemical stains are critical in arriving at the diagnosis.
PMID- 26425136
TI - Applying the Bradford Hill criteria in the 21st century: how data integration has
changed causal inference in molecular epidemiology.
AB - In 1965, Sir Austin Bradford Hill published nine "viewpoints" to help determine
if observed epidemiologic associations are causal. Since then, the "Bradford Hill
Criteria" have become the most frequently cited framework for causal inference in
epidemiologic studies. However, when Hill published his causal guidelines-just 12
years after the double-helix model for DNA was first suggested and 25 years
before the Human Genome Project began-disease causation was understood on a more
elementary level than it is today. Advancements in genetics, molecular biology,
toxicology, exposure science, and statistics have increased our analytical
capabilities for exploring potential cause-and-effect relationships, and have
resulted in a greater understanding of the complexity behind human disease onset
and progression. These additional tools for causal inference necessitate a re
evaluation of how each Bradford Hill criterion should be interpreted when
considering a variety of data types beyond classic epidemiology studies. Herein,
we explore the implications of data integration on the interpretation and
application of the criteria. Using examples of recently discovered exposure
response associations in human disease, we discuss novel ways by which
researchers can apply and interpret the Bradford Hill criteria when considering
data gathered using modern molecular techniques, such as epigenetics, biomarkers,
mechanistic toxicology, and genotoxicology.
PMID- 26425138
TI - Is whole gland salvage cryotherapy effective as palliative treatment of
haematuria in patients with locally advanced prostate cancer? Results of a
preliminary case series.
AB - OBJECTIVES: Locally advanced prostate cancer may cause several complications such
as haematuria, bladder outlet obstruction, and renal failure due to the ureteral
obstruction. Various treatments have been suggested, including radiotherapy,
antifibrinolytics, bladder irrigation with alum solution, transurethral surgery
and angioembolization, none of which have proven effectiveness. In the last years
cryoablation has become a valid therapeutic option for prostate cancer. In our
experience we used this 'new' technique as haemostatic therapy. METHODS: We
selected four patients with gross haematuria affected by locally advanced hormone
refractory prostate cancer, who had already been treated with primary
radiotherapy. We used third-generation cryotherapy: under ultrasonographic
guidance, we inserted six cryoprobes, two in each of the vascular pedicles
reaching at least -60 degrees C, and three thermometers. We then induced two
freeze-thaw cycles. RESULTS: After the operation the haematuria stopped in all
patients and at 9-month follow up we observed a mean of four red cells (range
three to five) in the urinary sediment with no evidence of bacteriuria. Prostate
volume, prostate-specific antigen and postmicturition residue were significantly
reduced. Qmax improved significantly too. CONCLUSION: Our experience has given us
good results with minimal intra- and postoperative complications. We think that
haemostatic cryotherapy as a palliative approach for locally advanced prostate
cancer could represent a valid treatment option and more consideration could be
given to its use.
PMID- 26425139
TI - Clinical use of the beta3 adrenoceptor agonist mirabegron in patients with
overactive bladder syndrome.
AB - Mirabegron is a beta3 adrenoceptor agonist licensed for the treatment of
overactive bladder symptoms, such as urinary urgency or urgency incontinence.
beta3 adrenoceptor activation causes detrusor muscle relaxation, but mirabegron
may also act by binding other targets in the bladder, and it may also reduce
activity in sensory nerves. Phase III clinical trials (SCORPIO, ARIES, and
CAPRICORN) evaluated mirabegron at various doses, demonstrating reduction from
baseline to endpoint in mean incontinence episodes and mean number of
micturitions per 24 h (coprimary endpoints), along with health-related quality of
life and a range of secondary measures. Efficacy was seen in many patients who
had previously discontinued antimuscarinic therapy on the grounds of lack of
efficacy or poor tolerability. Treatment emergent adverse effects were documented
in a long-term study (TAURUS), mostly being of mild or moderate severity. The
most frequent adverse effects were hypertension, dry mouth, constipation, and
headache, with a lower incidence of dry mouth than for the antimuscarinic active
comparator. Efficacy and safety are not substantially different in older
patients. A urodynamic safety study in men showed no consistent effect on voiding
function, but a small increase in postvoid residual. Use of mirabegron in
combination with alpha-adrenergic blockers does not appear to increase adverse
effects. Dose reduction is needed in people with severe renal failure, or
moderate hepatic failure. Dose adjustment is not needed in relation to food
intake. Ongoing research is evaluating the potential for combination therapy with
antimuscarinics.
PMID- 26425140
TI - Tadalafil for lower urinary tract symptoms secondary to benign prostatic
hyperplasia: a review of clinical data in Asian men and an update on the
mechanism of action.
AB - Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, is approved worldwide for
the treatment of lower urinary tract symptoms secondary to benign prostatic
hyperplasia (BPH-LUTS). The purpose of this narrative review is to summarize the
clinical data on tadalafil 5 mg once-daily, primarily focusing on Asian men with
BPH-LUTS, and to update the current understanding of the mechanism of action
underlying PDE5 inhibition. Findings from studies have demonstrated that PDE5 is
highly expressed in the lower urinary tract and supporting vasculature, and that
PDE5 inhibition potentially decreases smooth muscle cell proliferation in the
prostate, relaxes smooth muscle in the prostate, bladder neck and supporting
vasculature, increases blood perfusion to the lower urinary tract, and modulates
bladder afferent nerve activity. A total of 11 larger, 12-week, double-blind,
randomized, placebo-controlled studies of tadalafil, including four Asian
studies, have been conducted globally, enrolling >3000 men with BPH-LUTS. In
addition, two long-term (42- and 52-week) studies enrolled 394 Japanese and 428
North American men, respectively, with BPH-LUTS. Overall, tadalafil 5 mg once
daily resulted in significant improvements in the change from baseline to
endpoint in total International Prostate Symptom Scores (IPSS), IPSS storage and
voiding subscores, and IPSS quality of life index compared with placebo.
Tadalafil was well tolerated and had a favorable safety profile. These findings
support tadalafil 5 mg once-daily for treating men, including Asian men, with BPH
LUTS.
PMID- 26425141
TI - Percutaneous biopsy for risk stratification of renal masses.
AB - The increased use of abdominal imaging has led to identification of more patients
with incidental renal masses, and renal mass biopsy (RMB) has become a popular
method to evaluate unknown renal masses prior to definitive treatment. Pathologic
data obtained from biopsy may be used to guide decisions for treatment and may
include the presence or absence of malignant tumor, renal cell cancer subtype,
tumor grade and the presence of other aggressive pathologic features. However,
prior to using RMB for risk stratification, it is important to understand whether
RMB findings are equivalent to pathologic analysis of surgical specimens and to
identify any potential limitations of this approach. This review outlines the
advantages and limitations of the current studies that evaluate RMB as a guide
for treatment decision in patients with unknown renal masses. In multiple series,
RMB has demonstrated low morbidity and a theoretical reduction in cost, if
patients with benign tumors are identified from biopsy and can avoid subsequent
treatment. However, when considering the routine use of RMB for risk
stratification, it is important to note that biopsy may underestimate risk in
some patients by undergrading, understaging or failing to identify aggressive
tumor features. Future studies should focus on developing treatment algorithms
that integrate RMB to identify the optimal use in risk stratification of patients
with unknown renal masses.
PMID- 26425142
TI - Cytoreductive nephrectomy and its role in the present-day period of targeted
therapy.
AB - The beneficial effect of cytoreductive nephrectomy on survival of patients with
metastatic renal cell carcinoma in the immunotherapy era was based on two
prospective randomized trials. Unfortunately, such evidence does not yet exist in
the present-day period of targeted therapy. Despite this, cytoreductive
nephrectomy remains integral in the multimodal management of patients with
metastatic renal cell carcinoma. Multiple retrospective studies as well as data
from prospective studies examining targeted therapy support the continued use of
cytoreductive nephrectomy in the properly selected patient. Ongoing studies will
hopefully fine-tune the role and timing of cytoreductive nephrectomy in the
context of targeted therapy.
PMID- 26425143
TI - Clinical experience with everolimus in the second-line treatment of advanced
renal cell carcinoma.
AB - Everolimus is an oral inhibitor of mammalian target of rapamycin (mTOR-I) and is
currently approved for the treatment of metastatic renal cell carcinoma (mRCC)
after failure of first-line vascular endothelial growth factor receptor tyrosine
kinase inhibitor (TKI). In this narrative review, we aim to report the available
evidence about the use of everolimus as second-line therapy for mRCC. A
literature search was performed using PubMed/MEDLINE and abstracts from major
conferences on clinical oncology as sources. We report data from prospective as
well as retrospective and real world data studies and we analyze the safety and
efficacy profile of everolimus as second-line therapy for mRCC. Although
different drugs are currently available for the second-line treatment of mRCC,
everolimus represents a feasible and safe option in this setting, especially for
patients who have experienced high-grade toxicity or are still carrying TKI
related toxicities from first-line treatment.
PMID- 26425144
TI - Sterile pyuria: a forgotten entity.
AB - Sterile pyuria is a common entity. Yet there are no guidelines to address this
issue. We have conducted a systematic review over 20 years and reviewed the
results. Guidelines for assessment, diagnosis and management are developed based
on these results.
PMID- 26425145
TI - Mechanisms of immunological tolerance in central nervous system inflammatory
demyelination.
AB - Multiple sclerosis is a complex autoimmune disease of the central nervous system
that results in a disruption of the balance between pro-inflammatory and anti
inflammatory signals in the immune system. Given that central nervous system
inflammation can be suppressed by various immunological tolerance mechanisms,
immune tolerance has become a focus of research in the attempt to induce long
lasting immune suppression of pathogenic T cells. Mechanisms underlying this
tolerance induction include induction of regulatory T cell populations, anergy
and the induction of tolerogenic antigen-presenting cells. The intravenous
administration of encephalitogenic peptides has been shown to suppress
experimental autoimmune encephalomyelitis and induce tolerance by promoting the
generation of regulatory T cells and inducing apoptosis of pathogenic T cells.
Safe and effective methods of inducing long-lasting immune tolerance are
essential for the treatment of multiple sclerosis. By exploring tolerogenic
mechanisms, new strategies can be devised to strengthen the regulatory, anti
inflammatory cell populations thereby weakening the pathogenic, pro-inflammatory
cell populations.
PMID- 26425147
TI - Atherosclerosis in psoriatic disease: latest evidence and clinical implications.
AB - It is widely accepted that atherosclerosis is caused by chronic low-grade
inflammation that results from an interaction between immune mechanisms and
metabolic abnormalities within the vessel wall. Population-based studies have
found an increased cardiovascular risk in patients with psoriasis and psoriatic
arthritis (PsA). This risk is higher in patients with severe disease phenotypes,
such as those with severe psoriasis and with musculoskeletal inflammation. Higher
levels of inflammatory biomarkers also predict the development of clinical
cardiovascular events in these patients. The effect of medications used for PsA
on cardiovascular risk is limited to observational studies. Antitumor necrosis
factor agents and methotrexate have been associated with reduced cardiovascular
risk. These data highlight the importance of screening for cardiovascular risk
factors in these patients.
PMID- 26425146
TI - Making the next steps in psoriatic arthritis management: current status and
future directions.
AB - Psoriatic arthritis (PsA) is a chronic inflammatory condition with articular and
extra-articular manifestations: peripheral arthritis, axial disease, enthesitis,
dactylitis, and skin and nail disease. It is associated with cardiovascular
comorbidities. It is now recognized as a new entity, different from rheumatoid
arthritis and other spondyloarthritis in terms of clinical manifestations,
pathogenesis, and response to therapies. Anti-tumor necrosis factors (anti-TNFs)
have demonstrated clinical efficacies exceeding that of conventional disease
modifying antirheumatic drugs (DMARDs). The current treatment paradigms recommend
early diagnosis and treatment, and a strategic and target orientated approach,
aiming at a low disease activity status. New understanding in the
immunopathogenesis of PsA has led to new treatment targets. This review addresses
the evidence of current treatment for each of the domains as an aid to the
clinician managing these patients in the clinic. Some new therapeutic targets are
presented. We highlight the importance of development and validation in outcome
measures, including that of composite scores that capture various disease domains
that will facilitate future clinical trials to inform the best treatment.
PMID- 26425148
TI - Sarcoidosis: a rheumatologist's perspective.
AB - Sarcoidosis is a systemic disorder of unknown etiology, which may involve various
tissues and organs and is characterized by a noncaseating granuloma reaction.
While pathogenesis is not yet clear, cellular immune system activation and
nonspecific inflammatory response occur secondarily to several genetic and
environmental factors. T helper 1-cells and macrophage-derived pro-inflammatory
cytokines stimulate the inflammatory cascade and formation of granuloma occurs as
a result of tissue permeability, cell influx, and local cell proliferation. The
different prevalence, clinical results, and disease course observed in different
races and ethnic groups, is an indicator of the heterogeneous nature of the
disease. Sarcoidosis may mimic and/or may occur concomitantly with numerous
primary rheumatic diseases. This disease most commonly presents with bilateral
hilar lymphadenopathy, pulmonary infiltrations, and skin and eye lesions.
Locomotor system involvement is observed at a range of 15% and 25%. Two major
joint involvements have been described: acute and chronic form. The most common
form, the acute form, may be the first sign of sarcoidosis and present with
arthralgia, arthritis, or periarthritis. Chronic sarcoid arthritis is usually
associated with pulmonary parenchymal disease or other organ involvement and
occurs rarely. While asymptomatic muscular involvement is reported between 25%
and 75%, symptomatic muscular involvement is very rare. Symptomatic myopathy may
present as three different types: chronic myopathy, palpable nodular myositis, or
acute myositis. Even if rare, 2-5% of cases may exhibit osseous involvement and
it is frequently associated with lupus pernio, chronic uveitis, and multisystemic
disease. Sarcoidosis was reported together with different rheumatologic diseases.
There are studies showing that sarcoidosis may mimic the clinical and laboratory
findings of these disorders. Nonsteroidal anti-inflammatory drugs and
corticosteroids are used for treating the symptoms of rheumatologic findings. In
patients who are unresponsive to corticosteroids, immunosuppressive and anti
tumor necrosis factor alpha drugs may be used. In this review, the incidence of
rheumatologic symptoms, the clinical findings, and the treatment of rheumatologic
manifestations of sarcoidosis are discussed.
PMID- 26425149
TI - Towards an understanding of the role of DNA methylation in rheumatoid arthritis:
therapeutic and diagnostic implications.
AB - The term 'epigenetics' loosely describes DNA-templated processes leading to
heritable changes in gene activity and expression, which are independent of the
underlying DNA sequence. Epigenetic mechanisms comprise of post-translational
modifications of chromatin, methylation of DNA, nucleosome positioning as well as
expression of noncoding RNAs. Major advances in understanding the role of DNA
methylation in regulating chromatin functions have been made over the past
decade, and point to a role of this epigenetic mechanism in human disease.
Rheumatoid arthritis (RA) is an autoimmune disorder where altered DNA methylation
patterns have been identified in a number of different disease-relevant cell
types. However, the contribution of DNA methylation changes to RA disease
pathogenesis is at present poorly understood and in need of further
investigation. Here we review the current knowledge regarding the role of DNA
methylation in rheumatoid arthritis and indicate its potential therapeutic
implications.
PMID- 26425150
TI - Volume change theory for syringomyelia: A new perspective.
AB - BACKGROUND: The etiopathogenesis of syringomyelia is still an enigma. The authors
present a novel theory based on fluid dynamics at the craniovertebral (CV)
junction to explain the genesis of syringomyelia (SM). The changes in volume of
spinal canal, spinal cord, central canal and spinal subarachnoid space (SSS) in
relation to the posterior fossa have been analysed, specifically during postural
movements of flexion and extension. The effect of fluctuations in volume of
spinal canal and its contents associated with cerebrospinal fluid (CSF) flow
dynamics at the CV junction have been postulated to cause the origin and
propagation of the syringomyelia. The relevant literature on the subject has been
reviewed and the author's theory has been discussed. CONCLUSION: Volume of spinal
canal in flexion is always greater than that in extension. Flexion of spine
causes narrowing of the ventral subarachnoid space (SAS) and widening of dorsal
SAS while extension causes reverse changes leading to fluid movement in dorsal
spinal SAS in flexion and ventral spinal SAS in extension. Cervical and lumbar
spinal region with maximum bulk hence maximum area and volume undergo maximum
deformation during postural changes. SSS CSF is the difference between the volume
of spinal canal and spinal cord, varies in flexion and extension which is
compensated by changes in posterior fossa (CSF) volume in normal circumstances.
Blocked SAS at foramen magnum donot permit spinal SAS CSF exchange which during
postural changes is compensated by cavitatory/cystic (syrinx) change at locations
in cervical and lumbar spine with propensity for maximum deformation.
Augmentation of posterior fossa volume by decompression helps by normalization of
this CSF exchange dynamics but immobilizing the spinal movement theoretically
will cease any dynamic volume changes thereby minimizing the destructive
influence of the fluid exchange on the cord. Thus, this theory strengthens the
rational of treating patients by either methodology.
PMID- 26425151
TI - Outcome of revascularization in moyamoya disease: Evaluation of a new
angiographic scoring system.
AB - BACKGROUND: Moyamoya disease (MMD) is a chronic progressive cerebrovascular
occlusive disease affecting commonly the anterior circle of Willis. Matushima
grade inadequately reflects the angiographic changes postrevascularization
procedure. AIMS: To analyze the clinical and angiographic outcome of
revascularization procedures (direct [ST-middle cerebral artery (MCA)
anastomosis] and indirect [encephalo-duro-arterio-myo-synangiosis (EDAMS)]) in
MMD and validate a new angiographic scoring system. MATERIALS AND METHODS:
Retrospective study included symptomatic patients of MMD who underwent
revascularization; both indirect and combined methods between January 2002 and
April 2012. Follow-up angiography was done after at least 3 months. We devised a
novel scoring system the "angiographic outcome score" (AOS) including reformation
of distal MCA and anterior cerebral artery, regression of basal moyamoya vessels,
leptomeningeal collaterals and overall perfusion. AOS was applied to the
angiograms independently by a neuroradiologist and a neurosurgeon that were
blinded toward its preoperative or postoperative status. RESULTS: Totally 33
patients underwent 36 EDAMS and 4 combined procedures (EDAMS + ST-MCA bypass).
The mean follow-up was 20 months. None had recurrent transient ischemic attack or
fresh infarct. Postoperative AOS was significantly higher than preoperative AOS.
The Spearman rho showed positive correlation between Matushima grade and
postoperative AOS. Significant regression of basal moyamoya vessels and increase
in number of loci of transdural collaterals was seen. CONCLUSIONS: EDAMS is a
simple yet effective method of revascularization in both pediatric as well as
adult age groups. AOS is a simple, precise and easily reproducible scoring
system, which reflects the favorable angiographic changes after
revascularization.
PMID- 26425152
TI - Attention and executive functions in microsurgically treated patients after
subarachnoid hemorrhage.
AB - OBJECTIVES: This research aimed to assess attention and executive functions in
subarachnoid hemorrhage (SAH) patients. METHODS: The prospective, controlled,
longitudinal study was conducted. There were two groups of patients (SAH and
lumbar microdiscectomy groups), and all of them were operated on by a single
neurosurgeon (KD) in the same institution. Preoperatively, SAH patients were in
the Hunt-Hess Grade I and II. They did not develop any focal neurological deficit
or hydrocephalus postoperatively. The patients were tested in 2-time points: 15
and 45 days after microsurgery with a battery of tests and questioners consisting
of the Trail Making Test, the Sustained Attention to Response Task, the Hayling
Sentence Completion Test, The Attention/Concentration test of Attention, the
Wechsler Adult Intelligence Scale (verbal part). Results between groups were
compared (sex, age; years of education and verbal IQ). RESULTS: It was found the
presence of lower attention and executive function test scores in the SAH group
of patients with a trend of improving during the time. CONCLUSION: The detailed
neuropsychological assessment of operated patients who sustained SAH and were
without the focal neurological deficit postoperatively, showed declination in
their attention and executive function with a trend of cognitive recovery as time
passes by.
PMID- 26425153
TI - Multiple glioblastomas: Are they different from their solitary counterparts?
AB - CONTEXT: Multiple glioblastomas (GBMs) have a reported incidence of 2-20%. AIMS:
We intend to study these subsets of GBMs to know whether these are similar to
their solitary counterparts. SETTING AND DESIGN: A retrospective study. MATERIALS
AND METHODS: We analyzed 7 cases of biopsy-proven multiple GBMs. Multiple GBMs
were described if there were >1 lesion which was at least 1 cm apart. The
clinical data, radiological features, histopathological and immunohistochemical
analysis and follow-up were recorded. RESULTS: The mean age was 45 years (range
17-69 years). All cases presented with features of raised intracranial pressure
(ICP). Totally, 3 cases presented with hemiparesis and 2 cases with altered
sensorium and generalized tonic clonic seizures each. The median Karnofsky
performance status (KPS) was 50. Mean duration of symptoms was 40 days. All
lesions were contrast enhancing (2 with homogenous enhancement and 5 had ring
enhancement). Total excision of the lesion causing mass effect was done in all
cases. Histopathologically, small cells were significantly present in 4 cases,
and satellitosis was seen in 5 cases. Glial fibrillary acidic protein (GFAP) was
absent in all cases in which small cells were significant. In these 4 cases, the
proliferation index ranged from 40% to 95%. Totally, 3 patients died within 2
months of surgery, whereas remaining 4 patients underwent chemo-radiotherapy.
CONCLUSIONS: We conclude that the cases usually present with features of raised
ICP and poor KPS. Histopathologically these lesions show significant small cell
population, satellitosis, and GFAP negativity.
PMID- 26425155
TI - Imaging characteristics of supratentorial ependymomas: Study on a large single
institutional cohort with histopathological correlation.
AB - BACKGROUND: Supratentorial ependymoma (STE) is a tumor whose unique clinical and
imaging characteristics have not been studied. Histopathologically, they resemble
ependymoma elsewhere. We retrospectively reviewed the imaging findings with
clinicopathological correlation in a large number of patients with STE to
identify these characteristics. MATERIALS AND METHODS: Computed tomography (CT)
magnetic resonance images (MRI), pathology reports, and clinical information from
41 patients with pathology-confirmed STE from a single institution were
retrospectively reviewed. CT and MRI findings including location, size, signal
intensity, hemorrhage, and enhancement pattern were tabulated and described
separately in intraventricular and intraparenchymal forms. RESULTS: STE was more
common in pediatric age group and intraparenchymal was more common than
intraventricular form. The most common presentation was features of raised
intracranial tension. There were equal numbers of Grade II and Grade III tumors.
The imaging characteristics in adult and pediatric age group were similar. The
tumor was large and had both solid and cystic components. Advanced imaging such
as diffusion, perfusion, and spectroscopy were suggestive of high-grade tumor.
Only differentiating factor between Grade II and Grade III was the presence of
calcification. 1234 rule and periwinkle sign which we have described in this
article may help characterize this tumor on imaging. CONCLUSION: This series
expands the clinical and imaging spectrum of STE and identifies characteristics
that should suggest consideration of this uncommon diagnosis.
PMID- 26425154
TI - Safe and accurate placement of thoracic and thoracolumbar percutaneous pedicle
screws without image-navigation.
AB - BACKGROUND: Percutaneous pedicle screw placement is now commonly used to treat
spinal instability. It is imperative, especially at thoracic levels, to avoid
damage to adjacent neurovascular structures. Although more technically demanding
when compared with the lumbar spine, we believe that the percutaneous placement
of thoracic pedicle screws can be performed safely without image-navigation.
PURPOSE: The purpose was to evaluate the safety of percutaneous pedicle screw
placement in the thoracic and thoracolumbar spine without image-navigation. STUDY
DESIGN/SETTING: A retrospective study at a single institution. PATIENT SAMPLE:
Patients over the age of 18 years who presented with degenerative disease, trauma
or tumor that required surgical stabilization. OUTCOME MEASURES: Our outcomes
included postoperative plain film X-rays and computerized tomography (CT).
MATERIALS AND METHODS: We performed a retrospective study of patients who
underwent percutaneous pedicle screw placement without image-navigation between
T2 and L2. RESULTS: Between 2005 and 2011, a total of 507 pedicle screws were
placed in 120 patients. The indications included trauma (17%), tumor (8%), and
degenerative conditions (75%). The mean age was 61.3 years (range: 20-81 years).
Fifty-seven percent were male, and 43% were female. The mean blood loss was 297
+/- 40 ml. All patients underwent postoperative anterior-posterior and lateral
films that showed safe placement of pedicle screws. Moreover, 57% of patients
underwent postoperative CT imaging. There was 1 (0.4%) medial breach and 13 (5%)
lateral breaches of the pedicle screw patients who underwent CT imaging as read
by an independent neuroradiologist. None of the breaches resulted in adverse
neurological sequelae either immediately after or at most recent follow-up.
CONCLUSION: Thoracic and thoracolumbar percutaneous pedicle screw placement can
be performed safely and accurately without image-navigation.
PMID- 26425156
TI - The AOSpine thoracolumbar spine injury classification system: A reliability and
agreement study.
AB - AIM: Recently, AOSpine trauma knowledge forum proposed the AOSpine thoracolumbar
injury classification (AOSTLIC) system and suggested that it was reliable.
However, reliability data from additional institutions for the AOSTLIC system are
not available. This study was to examine the reliability of the AOSTLIC system in
patients with thoracolumbar (TL) fractures. MATERIALS AND METHODS: Between August
2009 and June 2012, 56 patients with 74 levels traumatic TL spinal injuries were
recruited. Two classifiers, consisting of two spine surgeons, assessed clinical
and imaging data. Initially, one surgeon reviewed the data in order to classify
and calculate injury severity score according to the AOSTSIC system. This process
was repeated on a 5-week interval by another surgeon. Then we analyzed data for
intra-observer and inter-observer reliability using the kappa statistic (k).
Finally, validity was assessed using the known-groups comparison. RESULTS: The
mean age of patients was 59.5 +/- 11.5 years. The kappa values for the AOSTSIC
system for intra-observer and inter-observer reliability ranged from 0.83 to
0.89, indicating nearly perfect agreement agreements. Known-groups analysis
showed satisfactory results. The AOSTSIC system discriminated well between sub
groups of patients who differed in Oswestry disability index. CONCLUSION: The
findings showed that the morphologic classification in AOSTSIC system appears to
be reliable and reproducible classification.
PMID- 26425158
TI - The long-term efficacy of pedicular screw fixation in patients suffering from
thoracolumbar burst fractures without neurological deficit.
PMID- 26425157
TI - The long-term efficacy of pedicular screw fixation at patients suffering from
thoracolumbar burst fractures without neurological deficit.
AB - OBJECTIVES: Treatment of choice at stable burst fracture is still a matter of
debate. The aim of this study is assessment of health-related quality of life
(HRQOL) regarding short form-36 (SF-36) and its correlation with kyphosis in
patients affected by thoracolumbar burst fracture without neurological deficit
undergoing posterior short segment pedicular screw fixation. MATERIALS AND
METHODS: Twenty patients with thoracolumbar burst fractures without neurological
deficits, meeting our criteria were enrolled in this study. The patients
underwent short segment pedicular screw fixation. After 2 years of follow-up, the
outcome assessment was performed with evaluating HRQOL; SF-36. The mean +/-
standard deviation was measured at each eight category of SF-36 and compared with
normative values of Iran. The correlation of Cobb angle and body pain was
analyzed by linear regression. RESULTS: The study detected reduced quality of
life (QOL), with total mean of 49.7 +/- 14 and physical function grade of 61.2 +/
22 which was significantly lower than Iran normative reported as 85.9 +/- 19.
Fifty percent still suffered from moderate to severe pain and Cobb angle had no
statistically significant correlation with body pain. CONCLUSIONS: It seems that
surgical treatment could not improve pain related disability of patients with
stable thoracolumbar burst fracture at long term follow up.
PMID- 26425159
TI - Spinal tumors: Trends from Northern India.
AB - INTRODUCTION AND METHODS: We retrospectively analyzed 111 patients with spinal
tumors operated over a period of 9 years to observe the relative frequency of
different lesions, their clinical profile, functional outcome and prognostic
factors. 30/111 (27%) were extradural, 40/111 (36.1%) were intradural
extramedullary (IDEM) and 41/111 (36.9%) were intramedullary spinal cord tumors
(IMSCTs). Mean age at surgery was 30.81 years (range 1-73 years). The average
preoperative duration of symptoms was 16.17 months (15 days to 15 years). Major
diagnoses were ependymomas and astrocytomas in IMSCT group, schwanommas and
neurofibromas in IDEM group, and metastasis, lymphoma in extradural group. The
common clinical features were motor weakness in 78/111 (70.27%), sensory loss in
55/111 (49.54%), pain 46/111 (41.44%), and sphincter involvement in 47/111
(42.43%) cases. RESULTS: Totally, 88/111 (79.27%) patients had improvement in
their functional status, 17/111 (15.31%) remained same, and 6/111 (5.4%) were
worse at time of their last follow-up. The mean follow-up was 15.64 months (1.5
m(-10) years). Totally, 59 out of 79 patients, who were dependent initially, were
ambulatory with or without the aid. Most common complication was persistent pain
in 10/111 (9%) patients and nonimprovement of bladder/bowel symptoms in 7/111
(6.3%). One patient died 3 months after surgery. CONCLUSIONS: (1) Congenital
malformative tumors like epidermoids/dermoids (unrelated to spina bifida) occur
more frequently, whereas the incidence of spinal meningioma is less in developing
countries than western populations. (2) The incidence of intramedullary tumors
approaches to that of IDEM tumors. Intramedullary tumors present at a younger age
in developing countries. (3) Rare histological variants like primitive
neuroectodermal tumors should also be considered for histological differential
diagnosis of spinal tumors. (4) Preoperative neurologic status is the most
important factor related to outcome in spinal tumors.
PMID- 26425160
TI - Clinical profile and outcomes in brainstem glioma: An institutional experience.
AB - AIM OF THE STUDY: This study was to analyze the clinical outcomes of brain stem
glioma treated with radiation therapy (RT) in our institution. MATERIAL AND
METHODS: Records of 48 patients with brainstem glioma treated between January
2007 and January 2013 were reviewed. Demographic variables, clinical variables,
radiological findings and treatment details with respect to age, sex, location of
tumor ( pontine Vs non pontine ), signs and symptoms, RT dose, follow up period
and outcomes were recorded. Patients were subdivided into two groups based on
their age, age <15 years (Group I) and age >=15 yrs (Group II). RESULTS: The
median age at diagnosis was 10 years (range 4-50). Male to female ratio was
11:10. Of the 48 cases analyzed, 27 patients (56%) were in group I and 21 (44%)
were in group II. Radiologically, 90.5% had involvement of pons. 10 (21%)
patients received RT dose >60 Gy and 38 (79 %) patients received RT dose of 54-60
Gy. Median overall survival was 7months (range 3-44 months). Median overall
survival in Group I and Group II was 4 months and 10 months respectively (P =
0.042). CONCLUSIONS: Brain stem glioma in pediatric age group is associated with
worse outcomes than in adults.
PMID- 26425161
TI - Extracranial to intracranial by-pass anastomosis: Review of our preliminary
experience from a low volume center in Egypt.
AB - BACKGROUND: Cerebral revascularization is a useful microsurgical technique for
the treatment of steno-occlusive intracranial ischemic disease, complex
intracranial aneurysms that require deliberate occlusion of a parent artery and
invasive skull base tumors. We describe our preliminary experience with
extracranial-to-intracranial by-passes at a low volume center; and discuss
clinical indications and microsurgical techniques, challenges in comparison to
large advanced referral centers. MATERIALS AND METHODS: Twenty-seven patients
with hemodynamic ischemia or complex aneurysms or skull base tumors were operated
at Cairo University Hospitals in the period between May 2009 and June 2014. All
patients operated by a low flow by-pass were operated through a superficial
temporal artery to middle cerebral artery (MCA) anastomosis. All patients chosen
for a high flow by-pass were operated using a radial artery graft interposed
between the MCAs distally and the common or the external carotid artery
proximally. Patency was confirmed at the end of surgery using appearance on the
table and confirmed after surgery by transcranial color-coded duplex or computed
tomography angiography. All patient data were prospectively collected and
retrospectively analyzed at the end of surgery. RESULTS: Nineteen patients
(70.4%) were operated upon for flow augmentation and eight patients (29.6%) were
operated upon for flow replacement. A total of 30 anastomoses were performed. All
except one were patent which gives a patency rate of 96.3%. There was one death
in the present series resulting from a hyperperfusion syndrome. 89.5% of patients
with hemodynamic ischemia stopped having symptoms after surgery. All but one
patient operated for hemodynamic ischemia showed a considerable cognitive
improvement after surgery. None of the patients operated upon for flow
replacement showed improvement of oculomotor nerve function in spite of adequate
intraoperative decompression. All patients treated for flow replacement showed
the absence of recurrence on follow-up. CONCLUSION: Our initial results for both
low and high flow by-pass procedures in our low volume center indicate that such
complex surgical procedures are possible with results comparable to those
obtained in other larger referral centers throughout the world. This procedure
not only represents a more definitive treatment when compared to other
endovascular or radiation treatments but is also much less costly when compared
to other treatment modalities.
PMID- 26425162
TI - Treatment of arteriovenous malformation with high-flow fistula and bilateral
transverse-sigmoid sinuses stenosis resulting diffuse cortical vein engorgement
and symptoms resembling carotid-cavernous fistula.
AB - Patients harboring arteriovenous malformations (AVMs) may present with focal
neurological deficit, seizures, hemorrhage or be completely asymptomatic. This
diversity in manifestation of AVM is related to the individual characteristics of
AVMs such as size, location, configuration of feeding arteries, and drainage
veins. Treating the AVMs with high-flow fistula and downstream sinuses occlusion
is challenging. The authors reported their experience of treating this kind of
AVM. The high venous pressure caused diffuse cortical venous regurgitation and
engorgement of left superior ophthalmic vein and symptoms resembling carotid
venous fistula. To avoid possible reflux of embolization materials to cortical
veins and facilitate surgical treatment, the bilateral transverse sinuses were re
canalized first. The venous pressure was measured through left transverse sinus,
and it decreased significantly from 50 mmHg to 20 mmHg after bilateral sinus
stenting. The AVM was then embolized and excised uneventfully.
PMID- 26425163
TI - Ruptured concomitant dermoid cysts of conus medullaris and cervico medullary
junction.
AB - Cranio spinal dermoid tumors are rare, benign, slow growing congenital, cystic
uni or multi locular tumors, which arise from the inclusion of epithelial tissue
within the neural grove during embryonic development.[1] In this case report, we
present an uncommon presentation, of a case of concomitant dermoid cysts at conus
medullaris and cervico medullary junction that ruptured into the central canal.
PMID- 26425164
TI - Enigmatic intracranial cyst causing diplopia and trigeminal neuralgia.
AB - Chronic compression by intracranial cystic lesions can cause cranial nerve
palsies and bony changes. With the advent of imaging techniques, grossly accurate
diagnosis is possible. However, few cases do surprise the clinicians both intra,
and postoperatively. A 27-year-old male presented to us with complaints of double
vision for 4 months followed by sharp, shooting pain in the left V1 and V2
distribution for 1-month duration, on examination, he had left lateral palsy and
decreased pin prick and temperature sensation in V1 distribution. On computed
tomography scan, a cystic lesion noted which is isodense in the middle cranial
fossa with erosion of the underlying bone. On magnetic resonance imaging lesion
was iso to hyperintense on T1-Weighted and hyperintense on T2-Weighted,
brilliantly enhancing on contrast administration. Provisional diagnosis was
trigeminal schwannoma, left temporal craniotomy and total excision of the cyst
done. Histopathological examination showed cyst wall lined with collagen.
Postoperatively patient neuralgic pain subsided with persisting sixth nerve
palsy.
PMID- 26425165
TI - Rare occurrence of intracranial epidermoid tumor in an unusual location with
atypical radiological features.
AB - Intracranial epidermoid tumors are benign rare tumors that arise due to
dysembryogenesis. Thought rare, they have characteristic radiological features
such as their magnetic resonance imaging signal intensities and a typical
location. We present a rare case of intracranial epidermoid tumor in a young
female patient that was unusually located within the left frontal lobe and had
certain atypical radiological findings. Preoperatively, this lesion was
erroneously presumed to be a low grade glioma or a dermoid. Therefore, this case
report prompts us to include atypical epidermoid cyst in the list of differential
diagnosis for nonenhancing lobar tumors.
PMID- 26425166
TI - Giant hydatid cyst in the posterior fossa of a child.
AB - The hydatid cyst (HC) is endemic in Mediterranean region including Syria. The
central nervous system is involved in 2-3% of cases. HC in cerebellum is very
rare. We report a case that presented as an emergency for high intracranial
pressure and deteriorating Glascow coma scale. Close monitoring and precise
surgical management using Dowling's technique resulted in very good outcome with
full recovery. We highlight the need for very careful surgical treatment because
cyst rupture and secondary hydatidosis due to spillage of the cyst contents can
dramatically worsen the outcome. HC should be taken into consideration in
countries where hydatid infestation is endemic.
PMID- 26425167
TI - Rhabdoid meningioma in the petroclival region: An atypical meningioma in an
atypical site.
PMID- 26425168
TI - The unusual angiographic course of intracranial pseudoaneurysms.
AB - Although rare, traumatic intracranial pseudoaneurysms remain one of the most
difficult vascular lesions to diagnose and treat. A 55-year-old male patient
underwent endoscopic endonasal transphenoidal resection for a pituitary
macroadenoma. The operation was complicated by an arterial bleed. The initial
angiogram revealed pseudoaneurysm of the anterior choroidal artery. Although the
pseudoaneurysm completely disappeared on the second angiogram, it was
surprisingly found to have enlarged on the third angiogram. The lesion was
successfully treated with flow-diversion using a pipeline embolization device.
The present case demonstrates that the natural history of iatrogenic
pseudoaneurysms may be unpredictable and misleading. Traumatic pseudoaneurysms
should, therefore, be carefully followed when conservative treatment is elected
or when the lesion seems to have spontaneously regressed. Flow-diversion seems to
be a reasonable treatment option.
PMID- 26425169
TI - A case of early extraneural medulloblastoma metastases in a young adult.
AB - Extraneural metastases are a relatively rare manifestation of the primary brain
tumors, and a major part of the cases has been associated with initial
medulloblastoma. Herein, we present the case of a young female adult diagnosed
and operated for medulloblastoma. The patient developed extraneural metastases in
the first postoperative year. The condition exhibited an aggressive course of
development, and the applied treatment approaches were unable to halt its
progression. A short literature review identifies the predictive factors
determining both prognosis and treatability of the condition; the current
limitations and future perspectives of the treatment options are discussed.
PMID- 26425170
TI - Enchondroma of the cervical spine in young woman: A rare case report.
AB - Enchondroma is a type of benign cartilaginous bone tumor. Enchondroma of the
spine is very rare. There are only a few cases of enchondromas located in the
lamina of the cervical spine have been reported. Therefore, we report a case of
enchondroma in the cervical spine. A 24-year-old female patient presented with a
history of neck pain, restriction of neck movement, pain and numbness along the
right scapula, and weakness accompanied by wasting of the right hand. Presumptive
diagnoses included bony tumors such as an aneurysmal bone cyst or a giant cell
tumor. Radiologic examinations revealed a round tumor in the right lamina of C4
with extracortical extension and foramen of C4-5. C4 right hemilaminectomy and
facetectomy were performed with near complete removal of the tumor. On
histological examination, the tumor was confirmed to be an enchondroma. At the 6
month follow-up, a computed tomography scan showed no recurrence with good
alignment.
PMID- 26425171
TI - Incidental frontal lobe mixed density epidermoid tumor in a patient of head
injury: A rare case report.
AB - The incidence of the epidermoid tumor is approximately 0.2-1.8% of all
intracranial tumors. Epidermoid tumors are typically intradural, but extra-axial
in location and only rarely found within the brain substance. We are reporting
the first case of incidental mixed density frontal epidermoid tumor in a patient
of head injury. Difficulty in the preoperative diagnosis and uncommon
presentation of the intracranial epidermoid tumor prompted us to report this
case.
PMID- 26425172
TI - Spinal neural fibrolipoma: A case report and review of the literature.
AB - Neural fibrolipoma is characterized by infiltration of the epineurium by adipose
and fibrous tissue. Intradural spinal cases are extremely rare. We report an
unusual case of spinal neural fibrolipoma. A 31-year-old pregnant woman presented
due to weakness of right leg (muscle strength 2/5). Magnetic resonance (MR)
evaluation of the spine revealed an extramedullary intradural mass at the T1-T4
level. MR findings were suggesting a dermoid cyst or a lipoma. Subtotal surgical
excision of the tumor was done. Histopathological examination showed enlarged
nerve bundles infiltrated by fibroadipose tissue. Thus, the diagnosis of neural
fibrolipoma was established. One month after surgery, lumbar MR showed residual
tumor tissue, but successful decompression of the spinal cord. Six months after
surgery, the neurological examination, muscle strength 4/5 evaluated. Neural
fibrolipoma is characterized by infiltration of the epineurium by adipose and
fibrous tissue. The tissue grows between and around nerve bundles thereby causing
enlargement of the affected nerve. Neural fibrolipoma is a benign lesion with no
effective therapy. Surgical excision usually causes severe damage of the involved
nerve. Although spinal cases are extremely rare, it should be included in the
differential diagnosis of extramedullary intradural masses.
PMID- 26425173
TI - A rare case of neurofibromatosis - type 1.
AB - Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is an
autosomal dominant familial tumor syndrome. Glioblastoma is a malignant brain
tumor but is a rare occurrence in patients with NF1. Here, we report a rare
occurrence of glioblastoma in a 60-year-old man with NF1, who presented with
headache, neck pain, and gait unsteadiness of 3 days duration. He also had
postural hypotension. Motor examination revealed left hemiparesis. Multiple
subcutaneous soft swellings and multiple cafe-au-lait spots were seen all over
his body. He also had inguinal and axillary freckling. Abdominal imaging revealed
a right suprarenal mass suggestive of cystic pheochromocytoma. Brain imaging
revealed a predominantly cystic intra-axial right frontal space occupying lesion
(SOL) with enhancing solid component, perilesional edema, and mass effect. The
patient underwent laparoscopic removal of right adrenal mass after being
adequately "blocked" by an alpha blocker-prazosin. Thereafter, he underwent right
frontal craniotomy and gross total excision of right frontal infiltrative SOL.
The postoperative period was uneventful. Patient underwent adjuvant radiotherapy
and chemotherapy.
PMID- 26425174
TI - Multiple meningiomas consisting of fibrous meningioma, transitional meningioma,
and meningotheliomatous meningioma in one adult patient.
AB - Multiple histopathology of meningioma is a condition in which the patient has
more than one histopathology feature of meningioma in different intracranial
locations, with or without sign of neurofibromatosis. Meningiomas are the most
common, non-glial, primitive intracranial tumors; their prevalence among operated
tumors is around 13-19%. They may occur at any age, but have a peak incidence
around 45 years of age. The incidence of multiple intracranial meningiomas varies
from 1% to 10% in different series, and the frequency of multiple meningiomas
without neurofibromatosis was reported to be <3%.
PMID- 26425175
TI - "Giant" terminal myelocystocele: A rare variant of spinal dysraphism.
AB - Terminal myelocystocele (TMC) is a rare form of spinal dysraphism. They
constitute approximately 5% of skin covered lumbosacral masses. The TMC is
composed of a low-lying conus medullaris with cystic dilatation of caudal central
canal and a surrounding meningocele that extends from the conus to the skin. A 2
year-old female child presented with a large lumbosacral mass and weakness of
both lower limbs since birth. Magnetic resonance imaging revealed a giant TMC.
The child was operated on successfully. This is an interesting and rare case of
"giant" TMC with partial sacral agenesis.
PMID- 26425177
TI - New depsidones and isoindolinones from the mangrove endophytic fungus Meyerozyma
guilliermondii (HZ-Y2) isolated from the South China Sea.
AB - Three new depsidones, botryorhodines E-G (1-3), and two new isoindolinones,
meyeroguillines A and B (7 and 9), along with five known compounds were isolated
from an endophytic fungus Meyerozyma guilliermondii, derived from the mangrove
plant Kandelia obovata. Their structures were elucidated by 1D and 2D NMR
spectroscopy and high resolution mass spectrometry (HREIMS). Compounds 1-6
exhibited strong alpha-glucosidase inhibitory activity with IC50 values ranging
from 2.1 to 13.3 MUM. Moreover, kinetic studies of compounds 2 and 6 showed that
both of them were noncompetitive inhibitors of alpha-glucosidase.
PMID- 26425176
TI - New palladium-oxazoline complexes: Synthesis and evaluation of the optical
properties and the catalytic power during the oxidation of textile dyes.
AB - The present paper describes the synthesis of new palladium-oxazoline complexes in
one step with good to high yields (68-95%). The oxazolines were prepared from
enantiomerically pure alpha-aminoalcohols. The structures of the synthesized
palladium complexes were confirmed by NMR, FTIR, TOFMS, UV-visible spectroscopic
analysis and X-ray diffraction. The optical properties of the complexes were
evaluated by the determination of the gap energy values (E g) ranging between
2.34 and 3.21 eV. Their catalytic activities were tested for the degradation of
Eriochrome Blue Black B (a model of azo dyes) in the presence of an ecological
oxidant (H2O2). The efficiency of the decolorization has been confirmed via UV
visible spectroscopic analysis and the factors affecting the degradation
phenomenon have been studied. The removal of the Eriochrome reached high yields.
We have found that the complex 9 promoted 84% of color elimination within 5 min
(C 0 = 30 mg/L, T = 22 degrees C, pH 7, H2O2 = 0.5 mL) and the energetic
parameters have been also determined.
PMID- 26425178
TI - The synthesis of active pharmaceutical ingredients (APIs) using continuous flow
chemistry.
AB - The implementation of continuous flow processing as a key enabling technology has
transformed the way we conduct chemistry and has expanded our synthetic
capabilities. As a result many new preparative routes have been designed towards
commercially relevant drug compounds achieving more efficient and reproducible
manufacture. This review article aims to illustrate the holistic systems approach
and diverse applications of flow chemistry to the preparation of pharmaceutically
active molecules, demonstrating the value of this strategy towards every aspect
ranging from synthesis, in-line analysis and purification to final formulation
and tableting. Although this review will primarily concentrate on large scale
continuous processing, additional selected syntheses using micro or meso-scaled
flow reactors will be exemplified for key transformations and process control. It
is hoped that the reader will gain an appreciation of the innovative technology
and transformational nature that flow chemistry can leverage to an overall
process.
PMID- 26425180
TI - Intermolecular addition reactions of N-alkyl-N-chlorosulfonamides to unsaturated
compounds.
AB - N-Alkyl-N-chlorosulfonamides add to alkenes under copper(I) catalysis. In
reactions of styrene derivatives with terminal double bonds the addition products
were obtained in excellent yield and high regioselectivity. Lower yields are
obtained in addition reactions to non-aromatic alkenes. The reaction most likely
proceeds via a redox catalysis and amidyl radicals, a concerted mechanism has
been ruled out and a polar mechanism via chloronium ions would lead to the
opposite regiochemistry.
PMID- 26425179
TI - Synthesis of icariin from kaempferol through regioselective methylation and para
Claisen-Cope rearrangement.
AB - The hemisynthesis of the naturally occurring bioactive flavonoid glycoside
icariin (1) has been accomplished in eleven steps with 7% overall yield from
kaempferol. The 4'-OH methylation of kaempferol, the 8-prenylation of 3-O
methoxymethyl-4'-O-methyl-5-O-prenyl-7-O-benzylkaempferol (8) via para-Claisen
Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3, and the
glycosylation of icaritin (3) are the key steps.
PMID- 26425181
TI - A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4
naphthoquinones.
AB - A new and efficient method for the synthesis of hexahydropyrimidine-fused 1,4
naphthoquinones in one step with high yields from the reaction of lawsone with
1,3,5-triazinanes was developed.
PMID- 26425182
TI - Development of variously functionalized nitrile oxides.
AB - N-Methylated amides (N,4-dimethylbenzamide and N-methylcyclohexanecarboxamide)
were systematically subjected to chemical transformations, namely, N-tosylation
followed by nucleophilic substitution. The amide function was converted to the
corresponding carboxylic acid, esters, amides, aldehyde, and ketone upon
treatment with hydroxide, alkoxide, amine, diisobutylaluminium hydride and
Grignard reagent, respectively. In these transformations, N-methyl-N
tosylcarboxamides behave like a Weinreb amide. Similarly, N-methyl-5
phenylisoxazole-3-carboxamide was converted into 3-functionalized isoxazole
derivatives. Since the amide was prepared by the cycloaddition reaction of
ethynylbenzene and N-methylcarbamoylnitrile oxide, the nitrile oxide served as
the equivalent of the nitrile oxides bearing a variety of functional groups such
as carboxy, alkoxycarbonyl, carbamoyl, acyl and formyl moieties.
PMID- 26425183
TI - The chemical behavior of terminally tert-butylated polyolefins.
AB - The chemical behavior of various oligoenes 2 has been studied. The catalytic
hydrogenation of diene 3 yielded monoene 4. Triene 7 was hydrogenated to diene 8,
monoene 9 and saturated hydrocarbon 10. Bromine addition to 3 and 7 yielded the
dibromides 17 and 18, respectively, i.e., the oligoene system has been attacked
at its terminal olefinic carbon atoms. Analogously, the higher vinylogs 19 and 20
yielded the 1,8- and 1,10-bromine adduts 23 and 24, respectively, when less than
1 equivalent of bromine was employed. Treatment of tetraene 19 with excess
bromine provided tetrabromide 25. In epoxidation reactions, both with meta
chloroperbenzoic acid (MCPBA) and dimethyldioxirane (DMDO) two model oligoenes
were studied: triene 7 and tetraene 19. Whereas 7 furnished the rearrangement
product 31 with MCPBA, it yielded the symmetrical epoxide 32 with DMDO.
Analogously, 19 was converted to mono-epoxide 33 with MCPBA and to 34 with DMDO.
Diels-Alder addition of 7 with N-phenyltriazolinedione (PTAD) did not take place.
Extension of the conjugated pi-system to the next higher vinylog, 19, caused NPTD
addition to the symmetrical adduct 37 in good yield. Comparable results were
observed on adding NPTD (equivalent amount) to pentaene 20 and hexaene 21. Using
36 in excess provided the 2:1-adduct 40 from 21 and led to a complex mixture of
adducts from heptaene 22. With tetracyanoethylene (TCNE) as the dienophile,
tetraolefin 19 yielded the symmetrical adduct 43, although the reaction
temperature had to be increased. Pentaene 20 and hexaene 21 led to corresponding
results, adducts 44 and 45 being produced in acceptable yields. With nonaene 42
and TCNE the 2:1-adduct 48 was generated according to its spectroscopic data.
Exploratory photochemical studies were carried out with tetraene 19 as the model
compound. On irradiation this reacted with oxygen to the stable endo-peroxide 52.
PMID- 26425184
TI - Design and synthesis of fused polycycles via Diels-Alder reaction and ring
rearrangement metathesis as key steps.
AB - Atom efficient processes such as the Diels-Alder reaction (DA) and the ring
rearrangement metathesis (RRM) have been used to design new polycycles. In this
regard, ruthenium alkylidene catalysts are effective in realizing the RRM of bis
norbornene derivatives prepared by DA reaction and Grignard addition. Here, fused
polycycles are assembled which are difficult to produce by conventional synthetic
routes.
PMID- 26425185
TI - One-pot odourless synthesis of thioesters via in situ generation of thiobenzoic
acids using benzoic anhydrides and thiourea.
AB - An efficient and odourless procedure for a one-pot synthesis of thioesters by the
reaction of benzoic anhydrides, thiourea and various organic halides (primary,
allylic, and benzylic) or structurally diverse, electron-deficient alkenes
(ketones, esters, and nitriles) in the presence of Et3N has been developed. In
this method, thiobenzoic acids were in situ generated from the reaction of
thiourea with benzoic anhydrides, which were subjected to conjugate addition with
electron-deficient alkenes or a nucleophilic displacement reaction with alkyl
halides.
PMID- 26425187
TI - Synthesis of gamma-hydroxypropyl P-chirogenic (+/-)-phosphorus oxide derivatives
by regioselective ring-opening of oxaphospholane 2-oxide precursors.
AB - The synthesis of P-chirogenic (+/-)-phosphine oxides and phosphinates via
selective nucleophilic ring opening of the corresponding oxaphospholanes is
described. Two representative substrates: the phosphonate 2-ethoxy-1,2
oxaphospholane 2-oxide and the phosphinate 2-phenyl-1,2-oxaphospholane 2-oxide
were reacted with various Grignard reagents to produce a single alkyl/aryl
product. These products may possess further functionalities in addition to the
phosphorus center such as the gamma-hydroxypropyl group which results from the
ring opening and pi-donor moieties such as aryl, allyl, propargyl and allene
which originates from the Grignard reagent.
PMID- 26425186
TI - Selected synthetic strategies to cyclophanes.
AB - In this review we cover various approaches to meta- and paracyclophanes involving
popular reactions. Generally, we have included a strategy where the reaction was
used for assembling the cyclophane skeleton for further functionalization. In
several instances, after the cyclophane is made several popular reactions are
used and these are not covered here. We included various natural products related
to cyclophanes. To keep the length of the review at a manageable level the
literature related to orthocyclophanes was not included.
PMID- 26425188
TI - Surprisingly facile CO2 insertion into cobalt alkoxide bonds: A theoretical
investigation.
AB - Exploiting carbon dioxide as co-monomer with epoxides in the production of
polycarbonates is economically highly attractive. More effective catalysts for
this reaction are intensively being sought. To promote better understanding of
the catalytic pathways, this study uses density functional theory calculations to
elucidate the reaction step of CO2 insertion into cobalt(III)-alkoxide bonds,
which is also the central step of metal catalysed carboxylation reactions. It was
found that CO2 insertion into the cobalt(III)-alkoxide bond of [(2
hydroxyethoxy)Co(III)(salen)(L)] complexes (salen = N,N"-bis(salicyliden-1,6
diaminophenyl)) is exothermic, whereby the exothermicity depends on the trans
ligand L. The more electron-donating this ligand is, the more exothermic the
insertion step is. Interestingly, we found that the activation barrier decreases
with increasing exothermicity of the CO2 insertion. Hereby, a linear Bronsted
Evans-Polanyi relationship was found between the activation energy and the
reaction energy.
PMID- 26425189
TI - Synthesis and evaluation of the biostability and cell compatibility of novel
conjugates of nucleobase, peptidic epitope, and saccharide.
AB - This article reports the synthesis of a new class of conjugates containing a
nucleobase, a peptidic epitope, and a saccharide and the evalution of their
gelation, biostability, and cell compatibility. We demonstrate a facile synthetic
process, based on solid-phase peptide synthesis of nucleopeptides, to connect a
saccharide with the nucleopeptides for producing the target conjugates. All the
conjugates themselves (1-8) display excellent solubility in water without forming
hydrogels. However, a mixture of 5 and 8 self-assembles to form nanofibers and
results in a supramolecular hydrogel. The proteolytic stabilities of the
conjugates depend on the functional peptidic epitopes. We found that TTPV is
proteolytic resistant and LGFNI is susceptible to proteolysis. In addition, all
the conjugates are compatible to the mammalian cells tested.
PMID- 26425190
TI - Pd(OAc)2-catalyzed dehydrogenative C-H activation: An expedient synthesis of
uracil-annulated beta-carbolinones.
AB - An intramolecular dehydrogenative C-H activation enabled an efficient synthesis
of an uracil-annulated beta-carbolinone ring system. The reaction is simple,
efficient and high yielding (85-92%).
PMID- 26425191
TI - Spiro annulation of cage polycycles via Grignard reaction and ring-closing
metathesis as key steps.
AB - A simple synthetic strategy to C 2-symmetric bis-spiro-pyrano cage compound 7
involving ring-closing metathesis is reported. The hexacyclic dione 10 was
prepared from simple and readily available starting materials such as 1,4
naphthoquinone and cyclopentadiene. The synthesis of an unprecedented octacyclic
cage compound through intramolecular Diels-Alder (DA) reaction as a key step is
described. The structures of three new cage compounds 7, 12 and 18 were confirmed
by single crystal X-ray diffraction studies.
PMID- 26425192
TI - Design and synthesis of polycyclic sulfones via Diels-Alder reaction and ring
rearrangement metathesis as key steps.
AB - Here, we describe a new and simple synthetic strategy to various polycyclic
sulfones via Diels-Alder reaction and ring-rearrangement metathesis (RRM) as the
key steps. This approach delivers tri- and tetracyclic sulfones with six (n = 1),
seven (n = 2) or eight-membered (n = 3) fused-ring systems containing trans-ring
junctions unlike the conventional all cis-ring junctions generally obtained
during the RRM sequence. Interestingly the starting materials used are simple and
commercially available.
PMID- 26425193
TI - Tetrathiafulvalene-based azine ligands for anion and metal cation coordination.
AB - The synthesis and full characterization of two tetrathiafulvalene-appended azine
ligands, namely 2-([2,2'-bi(1,3-dithiolylidene)]-4-yl)-6-((2,4
dinitrophenyl)hydrazono)methyl)pyridine (L1) and 5-([2,2'-bi(1,3-dithiolylidene)]
4-yl)-2-((2,4-dinitrophenyl)hydrazono)methyl)pyridine (L2) are described. The
crystal structure of ligand L1 indicates that the ligand is completely planar
with the presence of a strong intramolecular N3-H3...O1 hydrogen bonding.
Titration experiments with inorganic anions showed that both ligands are suitable
candidates for the sensing of fluoride anions. Ligand L2 was reacted with a Re(I)
cation to yield the corresponding rhenium tricarbonyl complex 3. In the crystal
structure of the newly prepared electroactive rhenium complex the TTF is neutral
and the rhenium cation is hexacoordinated. The electrochemical behavior of the
three compounds indicates that they are promising for the construction of
crystalline radical cation salts.
PMID- 26425194
TI - Cross-metathesis reaction of alpha- and beta-vinyl C-glycosides with alkenes.
AB - Cross-metathesis of alpha- and beta-vinyl C-deoxyribosides and alpha-vinyl C
galactoside with various terminal alkenes under different conditions was studied.
The cross-metathesis of the former proceeded with good yields of the
corresponding products in ClCH2CH2Cl the latter required the presence of CuI in
CH2Cl2 to achieve good yields of the products. A simple method for the
preparation of alpha- and beta-vinyl C-deoxyribosides was also developed. In
addition, feasibility of deprotection and further transformations were briefly
explored.
PMID- 26425195
TI - Antioxidant potential of curcumin-related compounds studied by chemiluminescence
kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT
calculations.
AB - This study compares the ability to scavenge different peroxyl radicals and to act
as chain-breaking antioxidants of monomers related to curcumin (1):
dehydrozingerone (2), zingerone (3), (2Z,5E)-ethyl 2-hydroxy-6-(4-hydroxy-3
methoxyphenyl)-4-oxohexa-2,5-dienoate (4), ferulic acid (5) and their
corresponding C 2-symmetric dimers 6-9. Four models were applied: model 1 -
chemiluminescence (CL) of a hydrocarbon substrate used for determination of the
rate constants (k A) of the reactions of the antioxidants with peroxyl radicals;
model 2 - lipid autoxidation (lipidAO) used for assessing the chain-breaking
antioxidant efficiency and reactivity; model 3 - oxygen radical absorbance
capacity (ORAC), which yields the activity against peroxyl radicals generated by
an azoinitiator; model 4 - density functional theory (DFT) calculations at
UB3LYP/6-31+G(d,p) level, applied to explain the structure-activity relationship.
Dimers showed 2-2.5-fold higher values of k A than their monomers. Model 2 gives
information about the effects of the side chains and revealed much higher
antioxidant activity for monomers and dimers with alpha,beta-unsaturated side
chains. Curcumin and 6 in fact are dimers of the same monomer 2. We conclude that
the type of linkage between the two "halves" by which the molecule is made up
does not exert influence on the antioxidant efficiency and reactivity of these
two dimers. The dimers and the monomers demonstrated higher activity than Trolox
(10) in aqueous medium (model 3). A comparison of the studied compounds with DL
alpha-tocopherol (11), Trolox and curcumin is made. All dimers are characterized
through lower bond dissociation enthalpies (BDEs) than their monomers (model 4),
which qualitatively supports the experimental results.
PMID- 26425196
TI - A novel and widespread class of ketosynthase is responsible for the head-to-head
condensation of two acyl moieties in bacterial pyrone biosynthesis.
AB - The biosynthesis of photopyrones, novel quorum sensing signals in Photorhabdus,
has been studied by heterologous expression of the photopyrone synthase PpyS
catalyzing the head-to-head condensation of two acyl moieties. The biochemical
mechanism of pyrone formation has been investigated by amino acid exchange and
bioinformatic analysis. Additionally, the evolutionary origin of PpyS has been
studied by phylogenetic analyses also revealing homologous enzymes in Pseudomonas
sp. GM30 responsible for the biosynthesis of pseudopyronines including a novel
derivative. Moreover this novel class of ketosynthases is only distantly related
to other pyrone-forming enzymes identified in the biosynthesis of the potent
antibiotics myxopyronin and corallopyronin.
PMID- 26425197
TI - A new method for the synthesis of alpha-aminoalkylidenebisphosphonates and their
asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues.
AB - A convenient approach has been developed to alpha-aminoalkylidenebisphosphonates
and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues
by alpha-phosphonylation, alpha-phosphinylation or alpha-phosphinoylation of 1-(N
acylamino)alkylphosphonates, that, in turn, are easily accessible from N-acyl
alpha-amino acids. Effective electrophilic activation of the alpha-position of 1
(N-acetylamino)alkylphosphonates was achieved by electrochemical alpha
methoxylation of these compounds in methanol, mediated with NaCl, followed by
displacement of the methoxy group with triphenylphosphonium tetrafluoroborate to
give hitherto unknown 1-(N-acetylamino)-1-triphenylphosphoniumalkylphosphonate
tetrafluoroborates. The latter compounds react smoothly with trialkyl phosphites,
dialkyl phosphonites or alkyl phosphinites in the presence of Hunig's base and
methyltriphenylphosphonium iodide in a Michaelis-Arbuzov-like reaction to give
the expected alkylidenebisphosphonates, 1-phosphinylalkylphosphonates or 1
phosphinoylalkylphosphonates, respectively, in good yields.
PMID- 26425198
TI - Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl
deprotection/azide cycloaddition.
AB - Propargylamines are popular substrates for triazole formation, but
tetrasubstituted variants have required multistep syntheses involving
stoichiometric amounts of metal. A recent cyclohexanone-amine-silylacetylene
coupling forms silyl-protected tetrasubstituted propargylamines in a single
copper-catalyzed step. The development of the tandem silyl deprotection-triazole
formation reported herein offers rapid access to alpha-tetrasubstituted
triazoles. A streamlined two-step approach to this uncommon class of hindered
triazoles will accelerate exploration of their therapeutic potential. The
superior activity of copper(II) triflate in the formation of triazoles from
sensitive alkyne substrates extends to simple terminal alkynes.
PMID- 26425199
TI - Synthesis and spectroscopic properties of beta-triazoloporphyrin-xanthone dyads.
AB - A novel series of beta-triazoloporphyrin-xanthone conjugates and xanthone-bridged
beta-triazoloporphyrin dyads has been synthesized in moderate to good yields
through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of copper(II)
2-azido-5,10,15,20-tetraphenylporphyrin or zinc(II) 2-azidomethyl-5,10,15,20
tetraphenylporphyrin with various alkyne derivatives of xanthones in DMF
containing CuSO4 and ascorbic acid at 80 degrees C. Furthermore, these
metalloporphyrins underwent demetalation under acidic conditions to afford the
corresponding free-base porphyrins in good to excellent yields. After successful
spectroscopic characterization, these porphyrins have been evaluated for their
photophysical properties. The preliminary results revealed a bathochromic shift
in the UV-vis and fluorescence spectra of these porphyrin-xanthone dyads.
PMID- 26425200
TI - Why base-catalyzed isomerization of N-propargyl amides yields mostly allenamides
rather than ynamides.
AB - The base-catalyzed isomerization of N-propargylamides or carbamates may furnish N
allenyl compounds (allenamides/allencarbamates) or further evolve to N-alkynyl
compounds (ynamides or yncarbamates). The particular fate of this reaction varies
from experiment to experiment and there is no clear rule for predicting the
reaction outcome for a particular structure. With the support of ab initio and
DFT computations, this work shows that observed results can be explained by
assuming an exchange equilibrium between energetically close N-propargyl, allenyl
and N-alkynyl forms and that the reaction outcome correlates to a particular
equilibrium mixture. Due to the very small energy gap between the N-allenyl and N
alkynyl forms, small structural changes may easily alter the equilibrium
position, explaining the variety of observed experimental results. Based on CBS
QB3 computations, the omegaB97 functional provided reasonably accurate
isomerization energies and could successfully predict the experimentally observed
behavior for several examples from the literature.
PMID- 26425201
TI - Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)
hydroxyiminoerythronolide A.
AB - Three novel spiroketals were prepared by a one-pot transformation of 6-O-methyl
9(E)-hydroxyiminoerythronolide A. We present the formation of a [4.5]spiroketal
moiety within the macrolide lactone ring, but also the unexpected formation of a
10-C=11-C double bond and spontaneous change of stereochemistry at position 8-C.
As a result, a thermodynamically stable structure was obtained. The structures of
two new diastereomeric, unsaturated spiroketals, their configurations and
conformations, were determined by means of NMR spectroscopy and molecular
modelling. The reaction kinetics and mechanistic aspects of this transformation
are discussed. These rearrangements provide a facile synthesis of novel macrolide
scaffolds.
PMID- 26425202
TI - Consequences of the electronic tuning of latent ruthenium-based olefin metathesis
catalysts on their reactivity.
AB - Two ruthenium olefin metathesis initiators featuring electronically modified
quinoline-based chelating carbene ligands are introduced. Their reactivity in RCM
and ROMP reactions was tested and the results were compared to those obtained
with the parent unsubstituted compound. The studied complexes are very stable at
high temperatures up to 140 degrees C. The placement of an electron-withdrawing
functionality translates into an enhanced activity in RCM. While electronically
modified precatalysts, which exist predominantly in the trans-dichloro
configuration, gave mostly the RCM and a minor amount of the cycloisomerization
product, the unmodified congener, which preferentially exists as its cis-dichloro
isomer, shows a switched reactivity. The position of the equilibrium between the
cis- and the trans-dichloro species was found to be the crucial factor governing
the reactivity of the complexes.
PMID- 26425203
TI - Thermal properties of ruthenium alkylidene-polymerized dicyclopentadiene.
AB - Differential scanning calorimetry (DSC) analysis of ring opening methatesis
polymerization (ROMP) derived polydicyclopentadiene (PDCPD) revealed an
unexpected thermal behavior. A recurring exothermic signal can be observed in the
DSC analysis after an elapsed time period. This exothermic signal was found to be
proportional to the resting period and was accompanied by a constant increase in
the glass-transition temperature. We hypothesize that a relaxation mechanism
within the cross-linked scaffold, together with a long-lived stable ruthenium
alkylidene species are responsible for the observed phenomenon.
PMID- 26425204
TI - Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium-zinc
base and regioselectivity-computed CH acidity relationship.
AB - The synthesis of N-arylated pyrroles and indoles is documented, as well as their
functionalization by deprotonative metallation using the base in situ prepared
from LiTMP and ZnCl2.TMEDA (1/3 equiv). With N-phenylpyrrole and -indole, the
reactions were carried out in hexane containing TMEDA which regioselectively
afforded the 2-iodo derivatives after subsequent iodolysis. With pyrroles and
indoles bearing N-substituents such as 2-thienyl, 3-pyridyl, 4-methoxyphenyl and
4-bromophenyl, the reactions all took place on the substituent, at the position
either adjacent to the heteroatom (S, N) or ortho to the heteroatom-containing
substituent (OMe, Br). The CH acidities of the substrates were determined in THF
solution using the DFT B3LYP method in order to rationalize the experimental
results.
PMID- 26425205
TI - Tandem cross enyne metathesis (CEYM)-intramolecular Diels-Alder reaction (IMDAR).
An easy entry to linear bicyclic scaffolds.
AB - A new tandem cross enyne metathesis (CEYM)-intramolecular Diels-Alder reaction
(IMDAR) has been carried out. It involves conjugated ketones, esters or amides
bearing a remote olefin and aromatic alkynes as the starting materials. The
overall process enables the preparation of a small family of linear bicyclic
scaffolds in a very simple manner with moderate to good levels of
diastereoselectivity. This methodology constitutes one of the few examples that
employ olefins differently than ethylene in tandem CEYM-IMDAR protocols.
PMID- 26425206
TI - Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application
to the synthesis of SF5-substituted phenylboronic esters and iodobenzenes.
AB - Pyridine promotes dediazoniation of aryldiazonium tetrafluoroborates. The formed
aryl radicals were trapped with B2pin2, iodine, or tetrahydrofuran to afford
boronic esters, iodobenzenes and benzenes, respectively. The application to the
synthesis of (pentafluorosulfanyl)phenylboronic esters,
iodo(pentafluorosulfanyl)benzenes and (pentafluorosulfanyl)benzene is shown.
PMID- 26425207
TI - Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement
metathesis as key steps.
AB - A tricyclic lactam is reported in a four step synthesis sequence via Beckmann
rearrangement and ring-rearrangement metathesis as key steps. Here, we used a
simple starting material such as dicyclopentadiene.
PMID- 26425208
TI - The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine.
AB - A simple enantioselective synthetic procedure for the preparation of mianserin
and epinastine in optically pure form is described. The key step in the synthetic
pathway is the asymmetric reduction of the cyclic imine using asymmetric transfer
hydrogenation conditions.
PMID- 26425209
TI - Design and synthesis of hybrid cyclophanes containing thiophene and indole units
via Grignard reaction, Fischer indolization and ring-closing metathesis as key
steps.
AB - We demonstrate a new synthetic strategy to cyclophanes containing thiophene and
indole moieties via Grignard addition, Fischer indolization and ring-closing
metathesis as key steps.
PMID- 26425210
TI - Ruthenium indenylidene "1(st) generation" olefin metathesis catalysts containing
triisopropyl phosphite.
AB - The reaction of triisopropyl phosphite with phosphine-based indenylidene pre
catalysts affords "1(st) generation" cis-complexes. These have been used in
olefin metathesis reactions. The cis-Ru species exhibit noticeable differences
with the trans-Ru parent complexes in terms of structure, thermal stability and
reactivity. Experimental data underline the importance of synergistic effects
between phosphites and L-type ligands.
PMID- 26425211
TI - Tetrathiafulvalene chemistry.
PMID- 26425212
TI - Qualitative evaluation of regioselectivity in the formation of di- and tri-6-O
tritylates of alpha-cyclodextrin.
AB - The quantitative analysis of reaction products showed that the reaction of
6(A),6(D)-di-O-trityl-alpha-cyclodextrin (CD), AD-isomer, with trityl chloride in
pyridine at 55 degrees C gave 6(A),6(B),6(E)-tri-O-trityl-alpha-CD, the amount
of which was only 25% of that of simultaneously formed 6(A),6(B),6(D)-tri-O
trityl-alpha-CD. This indicates that the bulky trityl groups of glucopyranose-A
and -D (Glu-A and -D, respectively) in the AD-isomer mainly retard the additional
tritylation of the C(6)-OH of the adjacent glucopyranoses in a counter-clockwise
direction (Glu-F and -C, respectively). (1)H NMR spectra of the AD-isomer showed
that the O(6)-H and C(6)-H signals of Glu-C and -F are shifted upfield due to the
ring current of the trityl groups. Thus, it is concluded that the bulky trityl
groups on Glu-A and Glu-D are oriented to Glu-F and Glu-C, respectively, and
sterically retard additional tritylation on Glu-F and Glu-C. Similar steric
hindrance was also observed in the additional tritylations of mono-6-O-trityl
alpha-CD, 6(A),6(B)-di- and 6(A),6(C)-di-O-trityl-alpha-CD's.
PMID- 26425213
TI - Latent ruthenium-indenylidene catalysts bearing a N-heterocyclic carbene and a
bidentate picolinate ligand.
AB - A silver-free methodology was developed for the synthesis of unprecedented N
heterocyclic carbene ruthenium indenylidene complexes bearing a bidentate
picolinate ligand. The highly stable (SIPr)(picolinate)RuCl(indenylidene) complex
4a (SIPr = 1,3-bis(2-6-diisopropylphenyl)imidazolidin-2-ylidene) demonstrated
excellent latent behaviour in ring closing metathesis (RCM) reaction and could be
activated in the presence of a Bronsted acid. The versatility of the catalyst 4a
was subsequently demonstrated in RCM, cross-metathesis (CM) and enyne metathesis
reactions.
PMID- 26425214
TI - Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of
3-acetamido-3-deoxy-D-psicofuranose derivatives.
AB - A novel synthetic strategy leading to 3-acetamido-3-deoxy-D-psicofuranose 9 is
presented. The latter compound, after some manipulations, was transformed into
fully protected 3-acetamido-3-deoxy-D-psicofuranose 11 as a potential substrate
for the synthesis of N-acetylglucosaminyltransferase inhibitors designed by
computational methods. After the attempted thioglycosylation of 11 with EtSH in
the presence of BF3.OEt2, 2-methyloxazoline derivatives 13 and 14 were isolated.
PMID- 26425215
TI - Assessing value of innovative molecular diagnostic tests in the concept of
predictive, preventive, and personalized medicine.
AB - Molecular diagnostic tests drive the scientific and technological uplift in the
field of predictive, preventive, and personalized medicine offering invaluable
clinical and socioeconomic benefits to the key stakeholders. Although the results
of diagnostic tests are immensely influential, molecular diagnostic tests (MDx)
are still grudgingly reimbursed by payers and amount for less than 5 % of the
overall healthcare costs. This paper aims at defining the value of molecular
diagnostic test and outlining the most important components of "value" from
miscellaneous assessment frameworks, which go beyond accuracy and feasibility and
impact the clinical adoption, informing healthcare resource allocation decisions.
The authors suggest that the industry should facilitate discussions with various
stakeholders throughout the entire assessment process in order to arrive at a
consensus about the depth of evidence required for positive marketing
authorization or reimbursement decisions. In light of the evolving "value-based
healthcare" delivery practices, it is also recommended to account for social and
ethical parameters of value, since these are anticipated to become as critical
for reimbursement decisions and test acceptance as economic and clinical
criteria.
PMID- 26425216
TI - Perception, career choice and self-efficacy of UK medical students and junior
doctors in urology.
AB - INTRODUCTION: There is a growing concern about the reduced clinical exposure to
urology at undergraduate level in the United Kingdom. As a consequence, the
competencies of junior doctors are considered inadequate. The views of these
doctors in training towards urology remain under reported. METHODS: A modified
Delphi method was employed to construct a questionnaire. Given the rise of social
media as a platform for scientific discussion, participants were recruited via a
social networking site. Outcomes assessed included career preference, exposure to
urology, perceived male dominance, and confidence at core procedures. RESULTS: In
total, 412 and 66 responses were collected from medical students and junior
doctors, respectively. Overall, 41% of participants felt that they had received a
good level of clinical exposure to urology as part of their training and 15% were
considering a career in this speciality. Female students were significantly less
likely to consider urology as a career option (p < 0.01). Of these, 37% of the
students felt confident at male catheterization and 46% of students regarded
urology as a male-dominated speciality. CONCLUSIONS: Urology is perceived as male
dominated and is the least likely surgical speciality to be pursued as a career
option according to our survey. Increased exposure to urology at the
undergraduate level and dedicated workshops for core urological procedures are
needed to address these challenges.
PMID- 26425217
TI - Predictors of improvement in semen parameters after varicocelectomy for male
subfertility: A prospective study.
AB - INTRODUCTION: We aim to predict results of varicocelectomy on sperm density and
progressive motility using preoperative clinical, laboratory and radiological
data and to propose cut-off values for significant parameters. METHODS: This
prospective study was carried out between July 2011 and June 2014. We included
123 patients in our study. They were diagnosed with primary infertility with
varicocele, were scheduled for varicocelectomy, and completed their follow-up. We
excluded patients with azoospermia, total necrospermia, recurrent varicocele, and
pituitary hormonal abnormalities. Varicocele was diagnosed and graded by physical
examination and colour Doppler ultrasound. Semen analyses were completed
preoperatively and 6 months postoperatively. Microscopic subinguinal
varicocelectomy was done in all cases. Patient demographics, pre- and
postoperative clinical data (varicocele grade and semen parameters) were
statistically analyzed. RESULTS: The mean +/- standard deviation of age, body
mass index, and subfertility duration was 28.3 +/- 7.4 years, 29.1 +/- 2.7
kg/m(2), and 21.9 +/- 7.1 months, respectively. About 53% of our patients (n =
66) had bilateral varicocele, and unilateral disease was found in the other 57
(46.3%) cases. Varicocele grade I was diagnosed in 42 (34.1%) patients, while the
other 81 (65.9%) patients had grade II or III. Higher grades of varicocele,
preoperative total testosterone level, sperm density, and progressive motility
had a statistically significant impact on the outcome of varicocelectomy in
univariate testing. Multivariate logistic analysis revealed that grade of
preoperative varicocele (95% confidence interval [CI] 5.6-6.3, p = 0.007) and
sperm density (95% CI 2.7-1.6, p = 0.0035), and progressive motility (95% CI 1.1
2.3, p = 0.0123) are independent predictors of semen parameters improvement after
varicocelectomy. CONCLUSION: The grade of the varicocele, sperm density, and
progressive motility are major predictors of outcome in varicocelectomy. Cut-off
values of >8 million/mL and >18% for sperm density and progressive motility,
respectively, in men with varicocele grade II or III, indicate a successful
outcome.
PMID- 26425218
TI - Comparative effectiveness of adrenal sparing radical nephrectomy and non-adrenal
sparing radical nephrectomy in clear cell renal cell carcinoma: Observational
study of survival outcomes.
AB - INTRODUCTION: We compare the survival outcomes of patients with clear cell renal
cell carcinoma (RCC) treated with adrenal sparing radical nephrectomy (ASRN) and
non-adrenal sparing radical nephrectomy (NASRN). METHODS: We conducted an
observational study based on a composite patient population from two university
teaching hospitals who underwent RN for RCC between January 2000 and December
2012. Only patients with pathologically confirmed RCC were included. We excluded
patients undergoing cytoreductive nephrectomy, with loco-regional lymph node
involvement. In total, 579 patients (ASRN = 380 and NASRN = 199) met our study
criteria. Patients were categorized by risk groups (all stage, early stage and
locally advanced RCC). Overall survival (OS) and cancer-specific survival (CSS)
were analyzed for risk groups. Survival analysis was performed using Kaplan-Meier
curves and Cox proportional hazards regression. RESULTS: The median follow-up was
41 months (range: 12-157). There were significant benefits in OS (ASRN 79.5% vs.
NASRN 63.3%; p = 0.001) and CSS (84.3% vs. 74.9%; p = 0.001), with any
differences favouring ASRN in all stage. On multivariate analysis, there was a
trend towards worse OS (hazard ratio [HR] 1.759, 95% confidence interval [CI]
0.943-2.309, p = 0.089) and CSS (HR 1.797, 95% CI 0.967-3.337, p = 0.064) in
patients with NASRN (although not statistically significant). Of these patients,
only 11 (1.9%) had adrenal involvement. CONCLUSIONS: The inherent limitations in
our study include the impracticality of conducting a prospective randomized trial
in this scenario. Our observational study with a 13-year follow-up suggests ASRN
leads to better survival than NASRN. ASRN should be considered the gold standard
in treating patients with RCC, unless it is contraindicated.
PMID- 26425219
TI - Collecting (Bellini) duct carcinoma: A clinical study of a rare tumour and review
of the literature.
AB - INTRODUCTION: We report our 15-year experience of Collecting (Bellini) duct
carcinoma (CDC). We retrospectively analyzed patient and tumour characteristics,
clinical manifestations, surgical techniques, clinical outcomes, and salvage
therapies. METHODS: From January 1999 to December 2013, 1042 patients underwent
surgical resection of renal neoplasm. We examined all renal tumors and identified
10 cases (0.96%) of CDC. RESULTS: The study group included 8 men and 2 women,
with a median age of 62.5 years. Of these 10 patients, 9 were symptomatic (90%).
All patients were treated with open nephrectomy. The mean tumour size was 5.7 cm.
The pathologic stages were distributed as follows: pT1b in 2 patients (20%); pT2a
in 1 patient (10%); pT3a in 3 patients (30%); and pT3b in 4 patients (40%).
Grading was assessed according to Fuhrman scale as follows: grade II in 1 patient
(10%); grade III in 3 patients (30%); grade IV in 5 patients (50%); undetermined
grade in 1 patient (10%). Four patients (40%) relapsed locally. The median time
of local recurrence was 4.9 months. Distant metastases occurred in 9 patients
(90%): 4/9 at the time of diagnosis and 5/9 after nephrectomy. The median time of
distant metastases after surgery was 8.1 months. Six patients received
chemotherapy (gemcitabine plus platinum salts). Radiotherapy was performed in 5
patients. One patient had surgery because of local recurrence and 2 patients were
irradiated in the area of the local recurrence. The median overall survival was
7.6 months, and only 2 patients survived more than 2 years after the nephrectomy.
CONCLUSIONS: CDCs of the kidney are aggressive and they have a low survival rate.
All patients in our study experienced a relapse of their disease. Local
recurrence preceded distant metastases. Results of salvage treatments were poor.
PMID- 26425220
TI - Risk factors for hemorrhage requiring embolization after percutaneous
nephrolithotomy.
AB - INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the primary surgical
intervention in kidney stone management. Even though it is performed quite often,
the complication rates are also high. Arteriovenous fistulas following extended
hemorrhages after PCNL are one of the most serious complications of this
operation. Our main objective was to review the data of patients who required
angiography and embolization. METHODS: In total, we included 1405 patients who
underwent PCNL between 2007 and 2014. All patient data were retrospectively
reviewed. All patients went under PCNL using fluoroscopy. Following informed
consent, all hemorrhagic patients underwent angiography in the interventional
radiology department and embolization was performed in patients with a hemorrhage
focus point. RESULTS: A total of 147 patients (10.4%) required transfusion for
post-PCNL hemorrhages. Of them, 14 (0.99%) underwent angiography and embolization
(9 [64.2%] were male and 5 [35.8%] were female, with a mean age of 39.4 +/-
10.2). The remaining 133 patients were conservatively managed (81 [60.9%] males
and 52 [39.1%] females, with a mean age of 42.3 +/- 12.4). When the predicting
factors for angiography and embolization were reviewed, renal abnormalities and
the mean size of stones were significant in both univariate and multivariate
analysis (p < 0.001). CONCLUSION: Patients with extended and intermittent
hematuria should be monitored closely for hemodynamics; if there is an ongoing
necessity for transfusion, angiography should be considered.
PMID- 26425221
TI - Optimization of the current self-assembled urinary bladder model: Organ-specific
stroma and smooth muscle inclusion.
AB - INTRODUCTION: Due to the complications associated with the use of non-native
biomaterials and the lack of local tissues, bioengineered tissues are required
for surgical reconstruction of complex urinary tract diseases, including those of
the urinary bladder. The self-assembly method of matrix formation using
autologous stromal cells obviates the need for exogenous biomaterials. We aimed
at creating novel ex-vivo multilayer urinary tissue from a single bladder biopsy.
METHODS: After isolating urothelial, bladder stromal and smooth muscle cells from
bladder biopsies, we produced 2 models of urinary equivalents: (1) the original
one with dermal fibroblasts and (2) the new one with bladder stromal cells.
Dermal fibroblasts and bladder stromal cells were stimulated to form an
extracellular matrix, followed by sequential seeding of smooth muscle cells and
urothelial cells. Stratification and cellular differentiation were assessed by
histology, immunostaining and electron microscopy. Barrier function was checked
with the permeability test. Biomechanical properties were assessed with uniaxinal
tensile strength, elastic modulus, and failure strain. RESULTS: Both urinary
equivalents could be handled easily and did not contract. Stratified epithelium,
intact basement membrane, fused matrix, and prominent muscle layer were detected
in both urinary equivalents. Bladder stromal cell-based constructs had terminally
differentiated urothelium and more elasticity than dermal fibroblasts-based
equivalents. Permeation studies showed that both equivalents were comparable to
native tissues. CONCLUSIONS: Organ-specific stromal cells produced urinary
tissues with more terminally differentiated urothelium and better biomechanical
characteristics than non-specific stromal cells. Smooth muscle cells could be
incorporated into the self-assembled tissues effectively. This multilayer tissue
can be used as a urethral graft or as a bladder model for disease modelling and
pharmacotherapeutic testing.
PMID- 26425222
TI - Radiation therapy after radical prostatectomy: A single-centre radiation oncology
experience in trends of referral and treatment practices.
AB - INTRODUCTION: Our objective was to assess whether referral and treatment
practices have changed since publication of the Southwest Oncology Group (SWOG)
8794 Trial in 2009, the first randomized study to demonstrate an overall survival
advantage of adjuvant radiation therapy (RT) after radical prostatectomy (RP).
METHODS: We retrospectively reviewed all medical charts of men who received RT at
our institution between 2004 and 2014 following RP. All RT was conducted by a
single radiation oncologist (DT). We divided the cohort into 2 groups according
to first referral date before or after the SWOG 8794 trial publication (i.e.,
before 2010 and after 2010). RESULTS: Medical charts were available for 161/165
patients (97.6%). RP was performed at the same institution in 58% of cases. The
median time between surgery and first referral for RT decreased significantly
from 672 days (interquartile range [IQR] 295-1449) before 2010 to 300 days (IQR
225-1023) after 2010 (p = 0.04). This trend was associated with lower median
prostate-specific antigen (PSA) at RT referral (0.26 MUg/L [IQR 0.17-0.48] vs.
0.46 MUg/L [IQR 0.25-0.90], respectively; p = 0.001). Androgen-deprivation
therapy with RT nearly tripled over time from 13% before 2010 to 37% after 2010
(p = 0.003). Throughout the study period, the time interval between surgery and
RT initiation was positively correlated with pT-stage (p = 0.001), Gleason score
(p = 0.005) and PSA doubling time (p < 0.001). CONCLUSIONS: At our tertiary
referral academic institution, post-RP patients are notably referred earlier for
RT and at lower PSA values compared to men treated prior to 2010. Further study
is necessary to evaluate this impact on biochemical recurrence-free survival.
PMID- 26425223
TI - Demonstration of the direct impact of ketamine on urothelium using a tissue
engineered bladder model.
AB - INTRODUCTION: Ketamine is a common recreational drug. Severe lower urinary tract
symptoms associated with its consumption have been reported, but little is known
about the involved mechanisms. The effect of ketamine, which is excreted in
urine, was evaluated by its application on an in vitro three-dimensional human
tissue-engineered bladder model composed of an urothelium and a submucosa.
METHODS: Human urothelial cells were cultured with medium containing various
concentrations of ketamine and harvested at different times to obtain growth
curves. Using this model, specific activity of caspase-3 was measured to assess
the level of apoptosis induced by ketamine. Finally, a human tissue-engineered
bladder model was used. Urothelial cells were plated on a stromal layer made of
dermal fibroblasts and incubated at the air/liquid interface to allow their
differentiation. Ketamine was then put on the mature urothelium using paper or
agarose vectors for 48 hours. RESULTS: The presence of ketamine increased cells'
doubling times from 1.26 days for control to 1.38 days (p = 0.14) and 1.78 days
(p < 0.01) for the 0.5 mM and 1.5 mM concentrations, respectively. 5 mM and 10 mM
of ketamine led to decline in the major cell population. Exposure to 5 mM
ketamine induced apoptosis, confirmed by a 2.5-fold increase in capase-3 specific
activity from control (p = 0.03). The structure and cellular cohesion of the
urothelium on the three-dimensional model, especially in the intermediate layers,
were severely affected in a concentration dependant fashion with both vectors.
CONCLUSION: The presence of ketamine in the bladder directly damages the
urothelium through the induction of apoptosis.
PMID- 26425224
TI - Towards optimizing prostate tissue retrieval following holmium laser enucleation
of the prostate (HoLEP): Assessment of two morcellators and review of literature.
AB - INTRODUCTION: We assess different approaches to retrieve the enucleated adenoma
after transurethral enucleation of the prostate, particularly using the holmium
laser. METHODS: A retrospective review through our prospectively maintained
database was performed looking for safety and efficacy of two morcellators. The
enucleation phase of the holmium laser enucleation of the prostate (HoLEP) was
classically performed followed by retrieval of the intravesical adenoma using
either the Piranha (Wolf Inc., Knittlingen, Germany) or VersaCut (Lumenis)
morcellator. A PubMed-MEDLINE search was conducted for all transurethral
enucleation procedures and relevant data regarding methods of prostate tissue
retrieval were extracted. RESULTS: Strictly limiting the study to 3 reusable
blades with each morcellator, we performed 67 and 55 consecutive procedures with
Piranha and VersaCut, respectively. There was no significant difference between
the two morcellators regarding perioperative complications, apart from 5 bladder
mucosal injuries with the VersaCut (9%). Furthermore, there were similar
retrieved tissue weight, mechanical problems-rate, catheter-time and hospital
stay in both morcellators. However, the Piranha morcellator needed significantly
less morcellation-time, needed to use cold loop to remove non-morcellated pieces
and to score the adenoma by laser for better bite of the adenoma, and had a
higher median morcellation-rate 6.2 (rate: 2.8-12) g/min. Despite little
reporting on morcellation, we had data on the tissue retrieval rate (2.6 to 6.5
g/min with Piranha and 1.9 to 11 g/min with VersaCut. Furthermore, bladder
mucosal injury was reported in 1.4% and 0.7 to 5.7% with Piranha and VersaCut,
respectively; bladder perforation with VersaCut was experienced in about 0.1 to
1.5% of patients. Our study is limited by its non-randomization. CONCLUSION: The
Piranha morcellator was the most efficient and safe way to retrieve tissue after
a transurethral enucleation of a prostate adenoma.
PMID- 26425225
TI - Initial Canadian experience with robotic simple prostatectomy: Case series and
literature review.
AB - INTRODUCTION: Robotic-assisted simple prostatectomy (RASP) has been touted as an
alternative to open simple prostatectomy (OSP) to treat large gland benign
prostatic hyperplasia. Our study assesses our institution's experience with RASP
and reviews the literature. METHODS: We performed a retrospective chart review
from January 2011 to November 2013 of all patients undergoing RASP and OSP.
Operative and 90-day outcomes, including operation time, intraoperative blood
loss, length of hospital stay (LOS), transfusion requirements, and complication
rates, were assessed. RESULTS: Thirty-two patients were identified: 4 undergoing
RASP and 28 undergoing OSP. There was no difference in mean age at surgery (69.3
vs. 75.2 years; p = 0.17), mean Charlson Comorbidity Index (2.5 vs. 3.5; p =
0.19), and mean prostate volume on TRUS (239 vs. 180 mL; p = 0.09) in the robotic
and open groups, respectively. There was a significant difference in the mean
length of operation, with RASP exceeding OSP (161 vs. 79 min; p = 0.008). The
mean intraoperative blood loss was significantly higher in the open group (835.7
vs. 218.8 mL; p = 0.0001). Mean LOS was shorter in the RASP group (2.3 vs. 5.5
days; p = 0.0001). No significant differences were noted in the 90-day
transfusion rate (p = 0.13), or overall complication rate at 0% with RASP vs.
57.1% with OSP (p = 0.10). CONCLUSIONS: Our data suggest RASP has a shorter LOS
and lower intraoperative volume of blood loss, with the disadvantage of a longer
operating time, compared to OSP. It is a feasible technique and deserves further
investigation and consideration at Canadian centres performing robotic
prostatectomies.
PMID- 26425227
TI - The influence of membranous stretched urethral length and urethral circumference
on postoperative recovery of continence after radical prostatectomy: A pilot
study.
PMID- 26425226
TI - Treatment and outcome of fibroepithelial ureteral polyps: A systematic literature
review.
AB - INTRODUCTION: Fibroepithelial polyps of the ureter are rare. Cases and small
series are reported in the literature. The treatment of choice, outcome and
appropriate follow-up regimen remain unclear. METHODS: We conducted a systematic
literature review of papers reporting fibroepithelial polyps of the ureter in
adult patients. Articles published before 1980 were excluded. RESULTS: The search
yielded 144 papers, of which 68 met the inclusion criteria. A reference scan from
the included 68 yielded an additional 7 new articles. In total, our study
included 75 articles (68 + 7). A total of 134 patients were described. Most
patients had a single lesion (range: 1-10). The median length of the polyp was
4.0 cm (range: 0.4-17.0). The percentage of polyps resected endoscopically
increased from 0% before 1985 to 67% after 2005. Two perioperative complications
were reported in 72 procedures (2.8%): a deep venous thrombosis and a case of
mesenteric lymphadenopathy. Both of these occurred after open surgery. Follow-up
data were available for 57 patients. The median follow-up was 12 months (range: 1
180). Four patients (7.0%) developed recurrent complaints: 2 had urinary stones,
1 had a ureteral stricture and 1 had recurrence of the polyp. Three of these
events followed endoscopic resection, and occurred within a year after the
procedure. CONCLUSION: Endoscopic resection of fibroepithelial polyps seems to be
safe and effective. It is minimally invasive and should be considered the gold
standard where endoscopic expertise is available. We advise follow-up imaging by
computed tomographic intravenous urography after 3 months and ultrasound after 1
year to detect late complications.
PMID- 26425228
TI - More work needed in examining the relationship between mean platelet volume and
inflammation in varicocele pathophysiology.
PMID- 26425229
TI - Author response: The relationship between mean platelet volume and inflammation
in varicocele pathophysiology.
PMID- 26425230
TI - Renal cancer seeding metastases following retroperitoneoscopic-assisted
cryoablation: A case report.
AB - Nephron-sparing laparoscopy is the standard surgical treatment for clinical T1a
renal tumours. However, the laparoscopic technique brings in its specific
oncological safety concerns. Seeding metastases are reported: peritoneal
metastases, port-tract metastases, and (sub-) cutaneous metastases. The method of
laparoscopic assisted renal mass cryoablation is marked by the fact that
traumatic tumour tissue handling is unavoidable. This case report reviews the
rare occasion of seeding metastases in the retroperitoneal space following
laparoscopic cryoablation of a small renal mass. The primary tumour showed no
focal recurrence as reported by histological examination. The combination of two
events as harming the integrity of cancer tissue and gas-circulation leading to
the development of metastases in the retroperitoneal cavity is discussed. The
combination of iatrogenic harming cancer tissue integrity and CO2-circulation
leads to metastases in the retroperitoneal cavity. Therefore, we recommend
performing image-guided renal mass biopsies before considering cryoablative
surgery.
PMID- 26425231
TI - Androgen secreting giant adrenocortical carcinoma with no metastases: A case
report and review of the literature.
AB - Functional adrenocortical carcinoma (ACC) is a very rare disease with a poor
prognosis. Over half (60%) of ACCs bigger than 6 cm synthesize hormones; hormone
secreting ACCs generally include virilization, feminization or Cushing syndrome.
Besides, 82% of ACCs are metastatic at the time of diagnosis. While a 48-year-old
female patient was examined for abdominal pain and flushing, we detected a non
metastasizing mass (23 * 18 * 16 cm) in the adrenal lodge. The mass was extracted
en bloc during open exploration and its histopathology was reported as ACC. We
review the literature and report the largest androgen-producing, clinically
silent ACC mass cited in the literature so far.
PMID- 26425232
TI - Wunderlich syndrome as the first manifestation of an extraskeletal Ewing sarcoma.
AB - We recently encountered an extremely rare case of spontaneous perirenal
hemorrhage in a 34-year-old man. He initially had undergone radical nephrectomy
owing to suspicion of renal cell carcinoma. The final diagnosis was extraskeletal
Ewing sarcoma.
PMID- 26425233
TI - Sorafenib treatment for recurrent stage T1 bilateral renal cell carcinoma in
patients with Von Hippel- Lindau disease: A case report and literature review.
AB - Renal cell carcinoma (RCC) with Von Hippel-Lindau (VHL) syndrome is associated
with multiple recurrences and a young age at diagnosis. Therefore the primary
goal of treatment is to stabilize the disease, minimizing the surgical resection
and preserving the renal function in the patients with VHL who have developing
RCC nodules after initial treatment. This is the first case report of VHL
disease, with long-term stable disease, treated with a half dose of sorafenib
after surgical resection and radiofrequency ablation for multiple recurrent stage
T1 masses. We discuss the efficacy and safety of low-dose sorafenib treatment and
review RCC in a patient with VHL disease.
PMID- 26425234
TI - Tubulocystic renal cell carcinoma: Report of a rare case.
AB - Cystic neoplasms of the kidney are rare, and present a unique diagnostic
challenge. We report the case of an elderly male who presented with a large
cystic neoplasm, which was a diagnostic dilemma clinically and radiologically.
Histopathological examination showed a tumour composed of variably sized tubules
lined by atypical cells having large round nuclei with prominent nucleoli.
Hobnailing was seen at places. Tumour cells were immunopositive for
pancytokeratin, vimentin, CD10, CK19 and AMACR, confirming a diagnosis of
tubulocystic renal cell carcinoma (TC-RCC).
PMID- 26425235
TI - Paradoxical air embolism during percutaneous nephrolithotomy due to patent
foramen ovale: Case report.
AB - Paradoxical air embolism is a very rare complication associated with percutaneous
nephrolithotomy (PCNL). Incidence may be higher if patients also suffer from a
septal heart defect. We report the case of a 76-year old male who presented for
PCNL treatment of a right kidney lower calyceal calculus. During the procedure,
the patient developed signs and symptoms consistent with that of air embolism.
Intraoperative echocardiography confirmed the diagnosis. Subsequent
intraoperative and postoperative medical management was carried out and the
patient was discharged after recovery three days later. This case highlights the
importance of a rare but potentially fatal complication of PCNL.
PMID- 26425236
TI - Intracardiac migration of ureteral double-J stent: A case report and review.
AB - Ureteral double-J (DJ) stenting is a common urologic procedure in several
ureteral surgeries and has been used to manage ureteral obstructions during
pregnancy. It may result in early and late complications. We review a rare case
of migration of the DJ stent into the cardiovascular system in a pregnant female.
We also review the literature. The endoscopic procedure to remove this
displacement has been done postnatally with no adverse effects.
PMID- 26425237
TI - Ectopic scrotum: A unique case report.
AB - Ectopic scrotum is a rare congenital anomaly. Most common location is supra
inguinal. We present a case of left ectopic scrotum in a three year old boy with
no associated congenital anomalies, who underwent successful scrotoplasty and
orchiopexy.
PMID- 26425238
TI - Reproductive outcomes in men with karyotype abnormalities: Case report and review
of the literature.
AB - Reciprocal translocations of autosomal chromosomes are present in about 1/625
men, yet often there are no symptoms except primary infertility. Abnormal
segregation during meiosis often produces sperm and subsequent embryos with
unbalanced translocations that often ultimately result in spontaneous abortions.
We report on a 37-year-old man and his 39-year-old wife who complained of primary
infertility. Previous in vitro fertilization (IVF) had resulted in pregnancy, but
two spontaneous abortions. Upon chromosomal testing, the man was diagnosed with a
reciprocal translocation and his wife was diagnosed with mosaic Turner's
syndrome. Through testicular sperm extraction (TESE) and IVF with preimplantation
genetic screening (PGS), they succeeded in having two healthy children. Since men
with different karyotype abnormalities can have male infertility, we reviewed the
literature and summarized the reproductive outcomes for men with both autosome
and sex chromosomal karyotype abnormalities.
PMID- 26425239
TI - Salvage HIFU for biopsy confirmed local prostate cancer recurrence after radical
prostatectomy and radiation therapy: Case report and literature review.
AB - High-intensity focused ultrasound (HIFU) is a treatment option for low- and
intermediate-risk prostate cancer and more recently has been used as salvage
therapy after failed radiation therapy. We present a case of local recurrence
with biochemical failure after radical prostatectomy and salvage external beam
radiation therapy with salvage HIFU without biochemical recurrence at 20 months.
PMID- 26425240
TI - Upper urinary tract lipoma: A case report.
AB - Upper urinary tract (UUT) benign tumours are rare. We present a case of UUT
lipoma in a 41-year-old man with left flank pain. A computed tomographic
urography scan revealed an irregular thickening of the left renal collecting
system wall extending from the upper calices to the renal pelvis. The diagnosis
of UUT was made and the patient underwent a nephroureterectomy with bladder cuff
excision, as standard treatment. However, macroscopic and histological
examination revealed a lipomatous tumour with no sign of malignancy. To our
knowledge this is the first reported case of its kind of a UUT managed first with
a minimally invasive approach.
PMID- 26425241
TI - A novel approach for manual de-torsion of an atypical (outward) testicular
torsion with bedside Doppler ultrasonography guidance.
AB - A 17-year-old boy presented with right testicular torsion to the lateral side.
Torsion was diagnosed by physical examination; the colour Doppler ultrasonography
(CDU) confirmed right testicular torsion with minimal peripheral hydrocele.
Transverse and longitudinal examination of the spermatic cord with ultrasound and
CDU revealed a counter-clockwise testicular torsion. Manual de-torsion was
performed in a clockwise direction (720o) and testicular blood flow and the
neutral position of the spermatic cord were confirmed by CDU. We did not
encounter a residual twist of the spermatic cord upon surgical exploration. In
our experience, ultrasound and CDU may predict the direction of testicular
torsion and may allow appropriate management of cases prior to surgery.
PMID- 26425242
TI - Conservative treatment for Brucella testicular abscesses: A case report and
literature review.
AB - Brucellosis is a multi-organ infectious disease that can cause genitourinary
manifestations.1-4 The most common genitourinary manifestation is orchitis;2,4
however, intratesticular abscesses are a rare complication. Although surgery is
the standard treatment for intratesticular abscesses, medical therapy alone can
be successful. We report the case of a 36-year-old man with multiple testicular
abscesses caused by relapse of systemic brucellosis. The patient presented after
a history of treated systemic brucellosis with left testicular swelling and pain.
An ultrasound showed multiple small testicular abscesses, and the repeat diluted
brucella titer demonstrated the causative pathogen. The patient was successfully
treated with 3 months of oral targeted antibiotics, with no need for drainage or
orchiectomy.
PMID- 26425243
TI - Fungus ball and emphysematous cystitis secondary to Candida tropicalis: A case
report.
AB - Fungus ball and fungal emphysematous cystitis are two rare complications of
fungal urinary tract infection. A 53-year-old male patient presented with these
complications caused by Candida tropicalis simultaneously. The predisposing
factors were diabetes mellitus and usage of broad-spectrum antibiotics. The
fungus ball, measuring 3.5 * 2.0 cm on the left wall of the urinary bladder,
shrank significantly to 1.6 * 0.8 cm after 5 days of intermittent irrigation with
saline before surgery. With transurethral removal of the fungus ball and
antifungal treatment with fluconazole, the patient fully recovered. We conclude
that a bladder fungus ball and fungal emphysematous cystitis should always be
suspected in patients with diabetes mellitus with uncontrolled funguria and
abnormal imaging. Treatment should include a systemic antifungal therapy and
thorough surgical removal of the fungus ball. A systemic antifungal therapy
combined with a local irrigation with saline or antifungal drugs might help
decrease the dissemination of fungemia during an invasive manipulation.
PMID- 26425245
TI - The Origins of Jewish Guilt: Psychological, Theological, and Cultural
Perspectives.
AB - The idea that guilt and Judaism are closely interlinked has a long historical
legacy. After discussing recent work on anthropology and emotion focusing on
shame and guilt, we examine three theories purporting to account for this link:
psychoanalytic, theological, and guilt as a cultural stereotype particularly the
notion of the Jewish mother.
PMID- 26425244
TI - Chromophobe renal cell carcinoma recurrence in the ureter: A late presentation of
a rare metastasis.
AB - We describe a case of recurrence of chromophobe renal cell carcinoma 8 years
after successful surgical treatment of primary localized disease in the left
kidney. The primary tumour had exhibited neither gross nor histological evidence
of lymphovascular infiltration. The recurrence occurred in the residual left
ureteric stump - a finding that, to the best of our knowledge, has not previously
been reported.
PMID- 26425246
TI - Prophylactic Fresh Frozen Plasma Infusion is Ineffective in Reversing Warfarin
Anticoagulation and Preventing Delayed Intracranial Hemorrhage After Falls.
AB - BACKGROUND: Elderly patients, with considerable fall risk, are increasingly
anticoagulated to prevent thromboembolic disease. We hypothesized that a policy
of prophylactic fresh frozen plasma (FFP) infusion in patients having falls would
reverse vitamin K antagonists (VKAs) and that reversal would decrease delayed
intracranial hemorrhage (ICH). METHODS: A retrospective review of patients with
trauma admitted to a level 2 community trauma center was performed from January
2010 until November 2012. Inclusion criteria were: ground level fall (GLF) with
suspected head trauma, on VKA, an international normalized ratio (INR) of >1.5,
and a negative head computed tomography (CT). Patients were transfused with FFP
to a goal INR of <1.5 while observed. Patients were classified as reversed (REV)
if the lowest INR achieved within 4 to 24 hours after initial INR was <1.5 or
unreversed (NREV) if lowest INR achieved was >1.5. Chi-square and logistic
regression were performed. RESULTS: A total of 194 patients met the criteria. In
all, 43 (22%) patients were able to be REV, and 151 (78%) patients remained NREV.
Unreversed patients were male and younger (P < .05). There was no difference in
mean FFP received. Unreversed patients had a higher initial INR of 3.0 compared
to REV patients (2.5; P = .018). One patient developed a delayed ICH and belonged
to the REV group. CONCLUSION: The incidence of delayed hemorrhage was 0.5%. A
strategy of prophylactic FFP infusion was ineffective in VKA reversal. We
recommend against prophylactic infusion of FFP during a period of observation for
patients on VKA with suspected head trauma and a negative initial CT.
PMID- 26425247
TI - Facilitating Early-In-Day Discharge for Multiple Sclerosis Patients Treated With
Intravenous Methylprednisolone: A Quality Improvement Project.
AB - BACKGROUND AND PURPOSE: Delays in patient hospital discharge affect care value
through costs of prolonged length of stay and barriers to patient flow within the
hospital. We sought to facilitate early-in-day discharges (EIDDs) without
extending length of stay for inpatients with multiple sclerosis admitted for
acute exacerbations and treated with intravenous (IV) methylprednisolone.
METHODS: We developed a standardized admission order set, a provider checklist,
and a patient checklist to better coordinate in-hospital care and discharge
planning for patients with multiple sclerosis admitted for IV methylprednisolone
treatment. The order set allowed providers to enter an accelerated dosing
schedule of methylprednisolone, as appropriate, to ensure administration of the
final dose of methylprednisolone in the morning on the anticipated day of
discharge. We compared a prospective intervention cohort to a retrospective,
preintervention baseline cohort. RESULTS: At baseline (N = 25), 12.0% of patients
were EIDD compared to 40.7% of intervention patients (N = 27; P = .03). In all,
85.2% of intervention patients compared to 64.0% of baseline patients were
discharged on the same day as last methylprednisolone treatment (P = .11). No
difference was observed in median length of stay and 30-day readmission rate
between groups. CONCLUSIONS: Use of a standard admission order set as well as
provider and patient checklists can facilitate EIDD and hospital bed availability
without compromising care quality for a select group of neurology inpatients.
PMID- 26425248
TI - Cervical Myelopathy Caused by Injections into the Neck.
AB - Three cases of longitudinally extensive cervical myelopathies temporally
associated with neck injections are presented. The spinal cord injury was similar
radiographically, despite a number of different needle approaches and substances
injected. In recent years, there have been reports of an acute cervical
myelopathy immediately following an injection procedure in the neck. Various
explanations have been offered for this unfortunate complication, including (1)
direct injection into the cord leading to traumatic injury, (2) injection of
particulate matter into the arterial supply of the cord causing microvascular
embolism and spinal cord infarction, and (3) intraneural injection of the
chemical with centripetal spread of the injectant from the nerve trunk to the
substance of the cord. The merits of each of these 3 mechanisms in explaining
these cases are discussed. Albeit rare, acute cervical myelopathy should be
considered a potential complication from any deep injection of chemicals into the
neck.
PMID- 26425249
TI - Direct Invasion of the Optic Nerves, Chiasm, and Tracts by Cryptococcus
neoformans in an Immunocompetent Host.
AB - Cryptococcus spp is a common fungal infection and frequent cause of meningitis in
immunocompromised patients; however, immunocompetent patients are also at risk of
infection. Visual loss often occurs via elevated intracranial hypertension but
can rarely occur through direct optic nerve, chiasm, or tract invasion. We report
a case of a 38-year-old woman who presented with decreased acuity in both eyes.
She had generalized visual field constriction in the right eye and temporal
hemianopsia in the left eye. Magnetic resonance imaging of the brain and orbits
showed multiple areas of ill-defined enhancement in the optic chiasm and tracts
as well as in the diaphragmatic sella, prepontine and interpeduncular cisterns,
and along cranial nerves VI, VII, and VIII bilaterally. Initial cerebrospinal
fluid (CSF) showed 34 white blood cells, hypoglycorrhachia, and negative
cryptococcal antigen and bacterial and fungal cultures. A transphenoidal biopsy
of the dura and pituitary gland was unremarkable. Empiric steroids resulted in
marked improvement in visual acuity in both eyes, but while tapering steroids,
she developed rapid visual loss bilaterally. Repeat CSF performed 6 weeks later
demonstrated a cryptococcal antigen titer of 1:512. Retroactive staining of the
pituitary biopsy was positive for mucicarmine, a component of the polysaccharide
capsule of Cryptococcus spp. After induction therapy with amphotericin B and
flucytosine and 1 year of fluconazole, her visual acuity was 20/20 in both eyes.
In summary, Cryptococcus can affect immunocompetent patients and often presents
with insidious, chronic meningitis. Visual loss is common in cryptococcal
meningitis but usually results from fulminant papilledema related to elevated
intracranial pressure. In rare cases, direct nerve or chiasm infiltration by the
fungus results in vision loss.
PMID- 26425251
TI - Dabigatran-Associated Intracranial Hemorrhage: Literature Review and
Institutional Experience.
AB - Dabigatran etexilate is an oral direct thrombin inhibitor approved for prevention
of stroke and systemic embolization in patients with nonvalvular atrial
fibrillation and for the treatment of venous thromboembolism. Although dabigatran
has a favorable safety profile, predictable pharmacokinetics, fewer drug
interactions than warfarin, and does not require monitoring, clinical data
regarding dabigatran reversal are limited. In addition, currently available
laboratory assays allow measurement of the presence, but not extent, of
dabigatran-associated anticoagulation. Patient age, renal function, weight,
concurrent drug therapy, adherence, and concomitant disease states can affect
dabigatran's efficacy and safety. Management of dabigatran-related intracranial
hemorrhage must be approached on a case-by-case basis and include assessment of
degree of anticoagulation, severity of hemorrhage, renal function, timing of last
dabigatran dose, and risk of thromboembolic events. Initial management includes
dabigatran discontinuation and general supportive measures. Oral activated
charcoal should be administered in those who ingested dabigatran within 2 hours.
Four-factor prothrombin complex concentrates (4PCCs), activated PCC, or
recombinant activated factor VII use may be reasonable but is not evidence based.
Reserve fresh frozen plasma for patients with dilutional coagulopathy. If readily
available, hemodialysis should be considered, particularly in patients with
advanced kidney injury or excessive risk of thromboembolic events. More clinical
studies are needed to determine a standardized approach to treating dabigatran
associated intracranial hemorrhage. Institutional protocol development will
facilitate safe, efficacious, and timely use of the limited management options.
PMID- 26425250
TI - Neuro-Ophthalmological Emergencies.
AB - Neuro-ophthalmological emergencies constitute vision or life-threatening
conditions if diagnosis and treatment are not promptly undertaken. Even with
immediate therapy, these clinical entities carry a high rate of morbidity. They
may present with diplopia, visual loss, and/or anisocoria. Arteritic anterior
ischemic optic neuropathy is an ominous condition, which can cause permanent and
severe vision loss, stroke, or aortic dissection, requiring immediate steroid
therapy. Pituitary apoplexy may go unnoticed if only computed axial tomography is
performed. Diseases affecting the cavernous sinus and orbital apex region, such
as cavernous sinus thrombosis or mucormycosis, can give rise to simultaneous
vision loss and diplopia and, if not treated, may extend to the brain parenchyma
causing permanent neurological sequela. An isolated third nerve palsy may be the
harbinger of a cerebral aneurysm, carrying a significant risk of mortality.
Horner syndrome can be the initial presentation of a carotid dissection, an
important cause of stroke in the young adult. The neurohospitalist should be
familiar with the workup and management of neuro-ophthalmological emergencies.
PMID- 26425253
TI - The Reversal Sign: An Ominous Imaging Finding.
PMID- 26425252
TI - A 61-Year-Old Woman With Headaches and Aphasia.
PMID- 26425254
TI - A Tangled Web.
PMID- 26425255
TI - Differential Diagnosis of Restricted Diffusion of the Thalamus-Focus on Viral
Encephalitis.
PMID- 26425256
TI - Ictal Asystole in Focal Epilepsy: To Pace or Not to Pace?
AB - Ictal bradyarrhythmias are rare episodes occurring in patients with or without a
past cardiac history. These episodes go unnoticed unless the patient is monitored
on simultaneous video-electroencephalogram and 1-lead electrocardiogram.
Recognizing ictal bradyarrhythmias is important, since episodes may predispose
patients to sudden, unexplained death in epilepsy. We present 2 cases of ictal
asystole in patients with right temporal lobe epilepsy. The first patient had
seizures refractory to medical therapy and received a pacemaker. The seizures in
the second patient responded well to antiepileptic medication, and a pacemaker
was deferred. These cases highlight the differing cardiovascular treatment
options for ictal asystole.
PMID- 26425257
TI - The Use of Osteochondral Allograft Transplantation for Primary Treatment of
Cartilage Lesions in the Knee.
AB - OBJECTIVE: To assess the outcome of osteochondral allograft (OCA) transplantation
as the primary treatment for cartilage injury in patients with no previous
surgical treatment. STUDY DESIGN: Case series. Patients were identified in our
outcomes database. Patients undergoing primary OCA transplantation with no prior
surgical treatment and a minimum of 2 years follow-up were selected. Pain and
function were evaluated preoperatively and postoperatively. Patient satisfaction
was assessed. Reoperations following OCA transplantation were captured. Failure
was defined as revision OCA or conversion to arthroplasty. RESULTS: Fifty-five
patients (61 knees) were included in the analysis. The study consisted of 30
males and 25 females (mean age = 32.9 years; range = 15.7-67.8 years). The most
common diagnoses for the OCA transplantation were osteochondritis dissecans
(44.3%) and avascular necrosis (31.1%). Pain and function improved preoperatively
to postoperatively on all outcome scales (P < 0.01). The majority of patients
(86%) were "extremely satisfied" or "satisfied." OCA survivorship was 89.5% at 5
years and 74.7% at 10 years. At latest follow-up (mean = 7.6 years; range = 1.9
22.6 years), OCA remained in situ in 50 knees (82%). Eighteen knees (29.5%) had
further surgery; 11 OCA failures and 7 other surgical procedure(s). Of the failed
knees (mean time to failure = 3.5 years; range = 0.5-13.7 years), 8 were
converted to arthroplasty, 2 had OCA revisions, and 1 had a patellectomy.
CONCLUSIONS: OCA transplantation is an acceptable primary treatment method for
some chondral and osteochondral defects of the knee. Failure of previous
treatment(s) is not a prerequisite for OCA transplantation.
PMID- 26425258
TI - Cartilage Degeneration and Alignment in Severe Varus Knee Osteoarthritis.
AB - OBJECTIVES: The aim of this study was to examine the relationship between
cartilage, ligament, and meniscus degeneration and radiographic alignment in
severe varus knee osteoarthritis in order to understand the development of varus
knee osteoarthritis. DESIGN: Fifty-three patients (71 knees) with primary varus
knee osteoarthritis and who underwent total knee arthroplasty were selected for
this study. There were 6 men and 47 women, with 40 right knees and 31 left knees
studied; their mean age at operation was 73.5 years. The ligament, meniscus,
degeneration of joint cartilage, and radiographic alignments were examined
visually. RESULTS: The tibial plateau-tibial shaft angle was larger if the
condition of the cartilage in the lateral femoral condyle was worse. The
femorotibial angle and tibial plateau-tibial shaft angle were larger if the
conditions of the lateral meniscus or the cartilage in the lateral tibial plateau
were worse. CONCLUSION: Based on the results of this study, progression of varus
knee osteoarthritis may occur in the following manner: medial knee osteoarthritis
starts in the central portion of the medial tibial plateau, and accompanied by
medial meniscal extrusion and anterior cruciate ligament rupture, cartilage
degeneration expands from the anterior to the posterior in the medial tibial
plateau. Bone attrition occurs in the medial tibial plateau, and the femoro
tibial angle and tibial plateau-tibial shaft angle increase. Therefore, the
lateral intercondylar eminence injures the cartilage of the lateral femoral
condyle in the longitudinal fissure type. Thereafter, the cartilage degeneration
expands in the whole of the knee joints.
PMID- 26425259
TI - Depth-Dependent Glycosaminoglycan Concentration in Articular Cartilage by
Quantitative Contrast-Enhanced Micro-Computed Tomography.
AB - OBJECTIVE: A quantitative contrast-enhanced micro-computed tomography (qCECT)
method was developed to investigate the depth dependency and heterogeneity of the
glycosaminoglycan (GAG) concentration of ex vivo cartilage equilibrated with an
anionic radiographic contrast agent, Hexabrix. DESIGN: Full-thickness fresh
native (n = 19 in 3 subgroups) and trypsin-degraded (n = 6) articular cartilage
blocks were imaged using micro-computed tomography (MUCT) at high resolution
(13.4 MUm(3)) before and after equilibration with various Hexabrix bathing
concentrations. The GAG concentration was calculated depth-dependently based on
Gibbs-Donnan equilibrium theory. Analysis of variance with Tukey's post hoc was
used to test for statistical significance (P < 0.05) for effect of Hexabrix
bathing concentration, and for differences in bulk and zonal GAG concentrations
individually and compared between native and trypsin-degraded cartilage. RESULTS:
The bulk GAG concentration was calculated to be 74.44 +/- 6.09 and 11.99 +/- 4.24
mg/mL for native and degraded cartilage, respectively. A statistical difference
was demonstrated for bulk and zonal GAG between native and degraded cartilage (P
< 0.032). A statistical difference was not demonstrated for bulk GAG when
comparing Hexabrix bathing concentrations (P > 0.3214) for neither native nor
degraded cartilage. Depth-dependent GAG analysis of native cartilage revealed a
statistical difference only in the radial zone between 30% and 50% Hexabrix
bathing concentrations. CONCLUSIONS: This nondestructive qCECT methodology
calculated the depth-dependent GAG concentration for both native and trypsin
degraded cartilage at high spatial resolution. qCECT allows for more detailed
understanding of the topography and depth dependency, which could help diagnose
health, degradation, and repair of native and contrived cartilage.
PMID- 26425260
TI - Characterization of Tissue Response to Impact Loads Delivered Using a Hand-Held
Instrument for Studying Articular Cartilage Injury.
AB - OBJECTIVE: The objective of this study was to fully characterize the mechanics of
an in vivo impactor and correlate the mechanics with superficial cracking of
articular surfaces. DESIGN: A spring-loaded impactor was used to apply energy
controlled impacts to the articular surfaces of neonatal bovine cartilage. The
simultaneous use of a load cell and displacement sensor provided measurements of
stress, stress rate, strain, strain rate, and strain energy density. Application
of India ink after impact was used to correlate the mechanical inputs during
impact with the resulting severity of tissue damage. Additionally, a signal
processing method to deconvolve inertial stresses from impact stresses was
developed and validated. RESULTS: Impact models fit the data well (root mean
square error average ~0.09) and provided a fully characterized impact.
Correlation analysis between mechanical inputs and degree of superficial cracking
made visible through India ink application provided significant positive
correlations for stress and stress rate with degree of surface cracking (R (2) =
0.7398 and R (2) = 0.5262, respectively). Ranges of impact parameters were 7 to
21 MPa, 6 to 40 GPa/s, 0.16 to 0.38, 87 to 236 s(-1), and 0.3 to 1.1 MJ/m(3) for
stress, stress rate, strain, strain rate, and strain energy density,
respectively. Thresholds for damage for all inputs were determined at 13 MPa, 15
GPa/s, 0.23, 160 s(-1), and 0.59 MJ/m(3) for this system. CONCLUSIONS: This study
provided the mechanical basis for use of a portable, sterilizable, and
maneuverable impacting device. Use of this device enables controlled impact loads
in vitro or in vivo to connect mechanistic studies with long-term monitoring of
disease progression.
PMID- 26425261
TI - In Vitro Toxicity of Local Anesthetics and Corticosteroids on Chondrocyte and
Synoviocyte Viability and Metabolism.
AB - OBJECTIVE: There is growing concern that intra-articular injection of local
anesthetic and/or corticosteroids may cause significant morbidity, including
potential toxicity to chondrocytes and synoviocytes, after even a single
exposure. We demonstrate that full thickness canine chondral and synovial samples
exposed to various local anesthetics and corticosteroids exhibit decreased loss
of cell viability compared with prior in vitro studies using monolayer culture,
due to the protective effects of intact extracellular matrix and cell
heterogeneity. METHODS: Full-thickness cartilage and synovial explants were
obtained from canine cadavers and exposed in culture media to the following for
24 hours: 1% lidocaine, 0.5% lidocaine, 0.25% bupivacaine, 0.125% bupvacaine,
0.0625% bupivacaine, betamethasone acetate, methylprednisolone acetate,
triamcinolone acetonide, or culture media only (control). Cell viability was
determined on days 1 and 7 of culture using a microscopic live-dead and alamar
blue metabolic assays. RESULTS: Complete loss of chondrocyte and synoviocyte
viability was noted in the 1% and 0.5% lidocaine group, 0.25% and 0.125%
bupivacaine group, betamethasone group, and methylprednisolone groups after 1 and
7 days of culture. Treatment with 0.0625% bupivacaine and triamcinolone
demonstrated no decrease in cell viability or metabolism when compared to
negative control. CONCLUSIONS: In this canine explant model, 1% and 0.5%
lidocaine, 0.25% and 0.125% bupivacaine, betamethasone acetate, and
methylpresdnisolone acetate were severely chondrotoxic and synoviotoxic after a
single exposure, despite intact extracellular matrix. In contrast, chondrocytes
and synoviocytes exposed to 0.0625% bupivacaine and triamcinolone remained viable
after treatment. Further in vivo study is needed before definitive
recommendations can be made.
PMID- 26425262
TI - Repairing Osteochondral Defects of Critical Size Using Multiple Costal Grafts: An
Experimental Study.
AB - OBJECTIVE: To investigate the feasibility of repairing osteochondral defects of
critical size by performing mosaicplasty using multiple sliced costal cartilage
grafts, which enables repair of extensively injured knees using grafts from a
single rib. DESIGN: Critical osteochondral defects were prepared on the femoral
groove of skeletally mature Japanese white rabbits. Costal cartilage grafts from
a single rib were harvested and sliced into multiple segments (approximately 3-5
mm in length). The defects were left untreated or repaired by performing
mosaicplasty using costal cartilage grafts (with or without a longitudinal cut
along the middle). At 4 and 12 weeks after transplantation, International
Cartilage Repair Society macroscopic and histological grading was performed.
RESULTS: The macroscopic score and visual histological score were significantly
higher in the repaired groups than in the untreated group at 4 and 12 weeks after
surgery. Histological continuous integration between grafted costal cartilage and
host bone was observed in both repaired groups. CONCLUSIONS: The findings suggest
that costal cartilage might be a useful alternative source for chondral grafting.
We were able to repair large osteochondral defects by performing mosaicplasty
using multiple sliced costal cartilage grafts from a single rib.
PMID- 26425263
TI - An In Vitro Comparison of the Incorporation, Growth, and Chondrogenic Potential
of Human Bone Marrow versus Adipose Tissue Mesenchymal Stem Cells in Clinically
Relevant Cell Scaffolds Used for Cartilage Repair.
AB - AIM: To compare the incorporation, growth, and chondrogenic potential of bone
marrow (BM) and adipose tissue (AT) mesenchymal stem cells (MSCs) in scaffolds
used for cartilage repair. METHODS: Human BM and AT MSCs were isolated, culture
expanded, and characterised using standard protocols, then seeded into 2
different scaffolds, Chondro-Gide or Alpha Chondro Shield. Cell adhesion,
incorporation, and viable cell growth were assessed microscopically and following
calcein AM/ethidium homodimer (Live/Dead) staining. Cell-seeded scaffolds were
treated with chondrogenic inducers for 28 days. Extracellular matrix deposition
and soluble glycosaminoglycan (GAG) release into the culture medium was measured
at day 28 by histology/immunohistochemistry and dimethylmethylene blue assay,
respectively. RESULTS: A greater number of viable MSCs from either source adhered
and incorporated into Chondro-Gide than into Alpha Chondro Shield. In both cell
scaffolds, this incorporation represented less than 2% of the cells that were
seeded. There was a marked proliferation of BM MSCs, but not AT MSCs, in Chondro
Gide. MSCs from both sources underwent chondrogenic differentiation following
induction. However, cartilaginous extracellular matrix deposition was most marked
in Chondro-Gide seeded with BM MSCs. Soluble GAG secretion increased in
chondrogenic versus control conditions. There was no marked difference in GAG
secretion by MSCs from either cell source. CONCLUSION: Chondro-Gide and Alpha
Chondro Shield were permissive to the incorporation and chondrogenic
differentiation of human BM and AT MSCs. Chondro-Gide seeded with BM MSCs
demonstrated the greatest increase in MSC number and deposition of a
cartilaginous tissue.
PMID- 26425264
TI - Comparison of Efficacy of Endogenous and Exogenous IGF-I in Stimulating Matrix
Production in Neonatal and Mature Chondrocytes.
AB - OBJECTIVE: The goal of this study was to compare the efficacy of endogenous
upregulation of IGF-I by gene therapy and exogenous addition of insulin-like
growth factor I (IGF-I) in enhancing proteoglycan synthesis by skeletally mature
and neonatal chondrocytes. Chondrocyte transplantation therapy is a common
treatment for focal cartilage lesions, with both mature and neonatal chondrocytes
used as a cell source. Additionally, gene therapy strategies to upregulate growth
factors such as IGF-I have been proposed to augment chondrocyte transplantation
therapies. METHODS: Both skeletally mature and neonatal chondrocytes were exposed
to either an adeno-associated virus-based plasmid containing the IGF-I gene or
exogenous IGF-I. RESULTS: Analysis of IGF-I and glycosaminoglycan production
using a 4-parameter dose-response model established a clear connection between
the amount of IGF-I produced by cells and their biosynthetic response. Both
neonatal and mature chondrocytes showed this relationship, but the sensitivities
were quite different, with EC50 of 0.57 ng/mL for neonatal chondrocytes and EC50
of 8.70 ng/mL IGF-I for skeletally mature chondrocytes. CONCLUSIONS: These data
suggest that IGF-I gene therapy may be more effective with younger cell sources.
Both cell types were less sensitive to exogenous IGF-I than endogenous IGF-I.
PMID- 26425265
TI - Detection methods and clinical significance of free peritoneal tumor cells found
during colorectal cancer surgery.
AB - Peritoneal washing is now part of the standard clinical practice in several
abdominal and pelvic neoplasias. However, in colorectal cancer surgery, intra
peritoneal free cancer cells (IFCC) presence is not routinely investigated and
their prognostic meaning is still unclear. When peritoneal washing results are
positive for the presence of IFCC a worse outcome is usually expected in these
colorectal cancer operated patients, but it what is not clear is whether it is
associated with an increased risk of local recurrence. It is authors' belief that
one of the main reasons why IFCC are not researched as integral part of the
routine staging system for colon cancer is that there still isn't a diagnostic or
detection method with enough sensibility and specificity. However, the potential
clinical implications of a routine research for the presence IFCC in colon
neoplasias are enormous: not only to obtain a more accurate clinical staging but
also to offer different therapy protocols, based on the presence of IFCC. Based
on this, adjuvant chemotherapy could be offered to those patients found to be
positive for IFCC; also, protocols of proactive intraperitoneal chemotherapy
could be applied. Although presence of IFCC appears to have a valid prognostic
significance, further studies are needed to standardize detection and examination
procedures, to determine if there are and which are the stages more likely to
benefit from routine search for IFCC.
PMID- 26425266
TI - Need for simulation in laparoscopic colorectal surgery training.
AB - The dissemination of laparoscopic colorectal surgery (LCS) has been slow despite
increasing evidence for the clinical benefits, with a prolonged learning curve
being one of the main restrictions for a prompt uptake. Performing advanced
laparoscopic procedures requires dedicated surgical skills and new simulation
methods designed precisely for LCS have been established: These include virtual
reality simulators, box trainers, animal and human tissue and synthetic
materials. Studies have even demonstrated an improvement in trainees'
laparoscopic skills in the actual operating room and a staged approach to
surgical simulation with a combination of various training methods should be
mandatory in every colorectal training program. The learning curve for LCS could
be reduced through practice and skills development in a riskfree setting.
PMID- 26425267
TI - Management of afferent loop obstruction: Reoperation or endoscopic and
percutaneous interventions?
AB - Afferent loop obstruction is a purely mechanical complication that infrequently
occurs following construction of a gastrojejunostomy. The operations most
commonly associated with this complication are gastrectomy with Billroth II or
Roux-en-Y reconstruction, and pancreaticoduodenectomy with conventional loop or
Roux-en-Y reconstruction. Etiology of afferent loop obstruction includes: (1)
entrapment, compression and kinking by postoperative adhesions; (2) internal
herniation, volvulus and intussusception; (3) stenosis due to ulceration at the
gastrojejunostomy site and radiation enteritis of the afferent loop; (4) cancer
recurrence; and (5) enteroliths, bezoars and foreign bodies. Acute afferent loop
obstruction is associated with complete obstruction of the afferent loop and
represents a surgical emergency, whereas chronic afferent loop obstruction is
associated with partial obstruction. Abdominal multiple detector computed
tomography is the diagnostic study of choice. CT appearance of the obstructed
afferent loop consists of a C-shaped, fluid-filled tubular mass located in the
midline between the abdominal aorta and the superior mesenteric artery with
valvulae conniventes projecting into the lumen. The cornerstone of treatment is
surgery. Surgery includes: (1) adhesiolysis and reconstruction for benign causes;
and (2) by-pass or excision and reconstruction for malignant causes. However,
endoscopic enteral stenting, transhepatic percutaneous enteral stenting and
direct percutaneous tube enterostomy have the principal role in management of
malignant and radiation-induced obstruction. Nevertheless, considerable
limitations exist as a former Roux-en-Y reconstruction limits endoscopic access
to the afferent loop and percutaneous approaches for enteral stenting and tube
enterostomy have only been reported in the literature as isolated cases.
PMID- 26425268
TI - Response to chemoradiotherapy and lymph node involvement in locally advanced
rectal cancer.
AB - AIM: To establish the association between lymph node involvement and the response
to neoadjuvant therapy in locally advanced rectal cancer. METHODS: Data of 130
patients with mid and low locally advanced rectal adenocarcinoma treated with
neoadjuvant chemoradiation followed by radical surgery over a 5-year period were
reviewed. Tumor staging was done by endorectal ultrasound and/or magnetic
resonance imaging. Tumor response to neoadjuvant therapy was determined by T
downstaging and tumor regression grading (TRG). Pathologic complete response
(pCR) is defined as the absence of tumor cells in the surgical specimen (ypT0N0).
The varying degrees TRG were classified according to Mandard's scoring system.
The evaluation of the response is based on the comparison between previous
clinico-radiological staging and the results of pathological evaluation. chi (2)
and Spearman's correlation tests were used for the comparison of variables.
RESULTS: Pathologic complete response (pCR, ypT0N0, TRG1) was observed in 19
cases (14.6%), and other 18 (13.8%) had only very few residual malignant cells in
the rectal wall (TRG2). T-downstaging was found in 63 (48.5%). Mean lymph node
retrieval was 9.4 (range 0-38). In 37 cases (28.5%) more than 12 nodes were
identified in the surgical specimen. Preoperative lymph node involvement was seen
in 77 patients (59.2%), 71 N1 and 6 N2. Postoperative lymph node involvement was
observed in 41 patients (31.5%), 29 N1 and 12 N2, while the remaining 89 were N0
(68.5%). In relation to ypT stage, we found nodal involvement of 9.4% in ypT0-1,
22.2% in ypT2 and 43.7% in ypT3-4. Of the 37 patients considered "responders" to
neoadjuvant therapy (TRG1 and 2), there were only 4 N+ (10.8%) and the remainder
N0 (89.2%). In the "non responders" group (TRG 3, 4 and 5), 37 cases were N+
(39.8%) and 56 (60.2%) were N0 (P < 0.001). CONCLUSION: Response to neoadjuvant
chemoradiation in rectal cancer is associated with lymph node involvement.
PMID- 26425269
TI - Validation of a new scoring system: Rapid assessment faecal incontinence score.
AB - AIM: To implement a quick and simple test - rapid assessment faecal incontinence
score (RAFIS) and show its reliability and validity. METHODS: From March 2008
through March 2010, we evaluated a total of 261 consecutive patients, including
53 patients with faecal incontinence. Demographic and comorbidity information was
collected. In a single visit, patients were administered the RAFIS. The results
obtained with the new score were compared with those of both Wexner score and
faecal incontinence quality of life scale (FIQL) questionnaire. The patient
without influence of the surgeon completed the test. The role of surgeon was
explaining the meaning of each section and how he had to fill. Reliability of the
RAFIS score was measured using intra-observer agreement and Cronbach's alpha
(internal consistency) coefficient. Multivariate analysis of the main components
within the different scores was performed in order to determine whether all the
scores measured the same factor and to conclude whether the information could be
encompassed in a single factor. A sample size of 50 patients with faecal
incontinence was estimated to be enough to detect a correlation of 0.55 or better
at 5% level of significance with 80% power. RESULTS: We analysed the results
obtained by 53 consecutive patients with faecal incontinence (median age 61.55 +/
12.49 years) in the three scoring systems. A total of 208 healthy volunteers
(median age 58.41 +/- 18.41 years) without faecal incontinence were included in
the study as negative controls. Pearson's correlation coefficient between "state"
and "leaks" was excellent (r = 0.92, P < 0.005). Internal consistency in the
comparison of "state" and "leaks" yielded also excellent correlation (Cronbach's
alpha = 0.93). Results in each score were compared using regression analysis and
a correlation value of r = 0.98 was obtained with Wexner score. As regards FIQL
questionnaire, the values of "r" for the different subscales of the questionnaire
were: "lifestyle" r = -0.87, "coping/behaviour" r = -0.91, "depression" r = -0.36
and "embarrassment" r = -0.90, (P < 0.01). A multivariate analysis showed that
all the scoring systems measured the same factor. A single factor may explain
80.84% of the variability of FI, so all the scoring systems measure the same
factor. Patient's continence improves when RAFIS and Jorge-Wexner scores show low
values and when the values obtained in the FIQL questionnaire are high.
CONCLUSION: RAFIS is a valid and reliable tool to assess Faecal Incontinence.
PMID- 26425270
TI - Impact of surgical delay on outcomes in elderly patients undergoing emergency
surgery: A single center experience.
AB - AIM: To determine predisposing factors leading to surgical delay in elderly
patients with acute abdominal conditions and its impact on surgical outcomes.
METHODS: A retrospective review of a total of 144 patients aged 60 years and
older who had undergone emergency abdominal surgery between 2010 and 2013 at a
regional general hospital was analysed. The operations analysed were limited to
perforated or gangrenous viscus and strangulated hernia. Patient demographic
features, time taken to obtain a computed tomography scan, time taken to surgery
and the impact on postoperative morbidity and mortality were analysed. RESULTS:
The mean age was 70.5 +/- 9.1 years and median time taken to surgery was 9 h. The
overall mortality and complication rates (Clavien Dindo 3 and above) were 9% and
13.1% respectively. Diabetes mellitus was a significant predisposing factor which
had an impact on surgical delays. Delays in surgery more than 24 h led to higher
complication rates at 38.9% (P = 0.003), with multivariate analysis confirming it
as an independent factor. Delays in obtaining a computed tomography (CT) scan was
also shown to result in higher complication rates (Clavien Dindo 3 and above).
CONCLUSION: Delays in performing emergency surgery in elderly lead to higher
complication rates. Obtaining CT scans early also may facilitate prompt diagnosis
of certain abdominal emergencies where presentation is more equivocal and this
may lead to improved surgical outcomes.
PMID- 26425271
TI - Laying open (deroofing) and curettage under local anesthesia for pilonidal
disease: An outpatient procedure.
AB - AIM: To test the efficacy of lay open (deroofing, not excision) with curettage
under local anesthesia (LOCULA) for pilonidal sinus as an outpatient procedure.
METHODS: LOCULA procedure was done for all types of pilonidal disease. The
primary outcome measure was cure rate. The secondary outcome measures were
hospital stay, operating time, return to work, healing time and complication
rate. RESULTS: Thirty-three (M/F-30/3, mean age-23.4 +/- 5.8 years) consecutive
patients were operated and followed for 24 mo (6-46 mo). Eleven were pilonidal
abscess and 22 were chronic pilonidal disease. Six had recurrent disease.
Operating time and the hospital stay was 22.3 +/- 5.6 min and 63.8 +/- 22.3 min
respectively. The patients could resume normal work in 4.3 +/- 3.2 d and the
healing time was 42.9 +/- 8.1 d. Thirty (93.8%) patients had complete resolution
of the disease and two (6.2%) had a recurrence. Both the recurrences happened in
patients who had complete healing but ignored the prescribed recommendations. One
out of these got cured after getting operated again with the same procedure. Thus
the overall success rate of this procedure was 96.9%. CONCLUSION: Lay open
(deroofing) with curettage procedure under local anesthesia is an effective
procedure to treat both simple and complicated pilonidal sinus and abscess. It is
a simple procedure, has a high cure rate (up to 97%), doesn't require admission
and is associated with minimal morbidity and scarring. Considering the distinct
advantages, this procedure has the potential to become the first line procedure
for treating pilonidal disease.
PMID- 26425272
TI - Acute pancreatitis complicated with splenic rupture: A case report.
AB - Atraumatic splenic rupture is an uncommon complication of acute pancreatitis.
This report describes the case of a 30-year-old man with acute pancreatitis and
splenic vein thrombosis complicated by splenic rupture. The patient was admitted
to the emergency department with pain in the upper abdomen that had been present
for six hours and was associated with vomiting and sweating. He was diagnosed
with acute pancreatitis of alcoholic etiology. Upon computed tomography (CT) of
the abdomen, the pancreatitis was scored as Balthazar C grade, and a suspicious
area of necrosis affecting 30% of the pancreas with splenic vein thrombosis was
revealed. Seventy-two hours after admission, the patient had significant
improvement in symptoms. However, he showed clinical worsening on the sixth day
of hospitalization, with increasing abdominal distension and reduced hemoglobin
levels. A CT angiography showed a large amount of free fluid in the abdominal
cavity, along with a large splenic hematoma and contrast extravasation along the
spleen artery. The patient subsequently underwent laparotomy, which showed
hemoperitoneum due to rupture of the splenic parenchyma. A splenectomy was then
performed, followed by ultrasound-guided percutaneous drainage.
PMID- 26425273
TI - Hematopoietic effect of deer antler extract fermented by Bacillus subtilis on
murine marrow cells.
AB - BACKGROUND/OBJECTIVES: We examined the chemical composition and the effect of
fermented deer antler on hematopoietic factors in bone marrow cells.
MATERIALS/METHODS: For the preparation of fermented deer antler extract (FAB),
fermentation was carried out using Bacillus subtilis at 30C for 7 days. The
hematopoietic effect of FAB was investigated hematopoietic factors in marrow
cells. RESULTS: The contents of total sugar, sulfated glycosaminoglycans, and
uronic acid and the dry weight gradually increased with fermentation time. The
sialic acid content (from 0.14 mg/mL to 0.54 mg/mL) was the highest on the 4th
day of fermentation after which it decreased. The proliferating activity of bone
marrow cells increased with fermentation times. The levels of various
hematopoietic growth factors were determined to verify the beneficial effect of
deer antler extract fermented by B. subtilis on hematopoiesis. FAB increased the
number of stem cell factors and granulocyte colony-stimulating factor in bone
marrow cells. In addition, FAB augmented the burst-forming unit erythroid and
total colonies in splenocyte-conditioned medium compared with non-fermented
antler extract (NFA). However, FAB did not affect the mRNA levels of
erythropoietin, an important factor for erythropoiesis. CONCLUSIONS: FAB, like
NFA, did not directly affect hematopoiesis, but contributed to hematopoiesis by
stimulating the production of hematopoietic factors.
PMID- 26425274
TI - St. John's Wort (Hypericum perforatum) stimulates human osteoblastic MG-63 cell
proliferation and attenuates trabecular bone loss induced by ovariectomy.
AB - BACKGROUND/OBJECFTIVES: The effect of St. John's Wort extract (SJW) on MG-63 cell
proliferation and trabecular bone loss induced by ovariectomy was examined.
MATERIALS/METHODS: Proliferation, expression of estrogen receptor (ER) alpha and
ER beta, and gene expressions of osteoprotegerin (OPG), osteocalcin (OC) and
alkaline phosphatase (ALP) were examined in MG-63 cells treated with or without
SJW. Ovariectomized rats were treated with SJW at the dose of 100 or 200
mg/kg/day, beta-estradiol-3-benzoate (E2), or vehicle only (OVX-C), and sham
operated rats were treated with vehicle only (Sham-C). Serum ALP and C
telopeptide (CTX), and femoral trabecular bone loss were examined. RESULTS: SJW
increased MG-63 cell proliferation and expression of ER alpha and ER beta, and
positive effect was shown on gene expressions of ALP, OC and OPG. SJW also showed
estrogen like effect on bone associated with slowing down in trabecular bone
loss. Histopathology by H&E showed rats treated with SJW displayed denser
structure in metaphyseal region of distal femur compared with rats in OVX-C. SJW
was shown to reduce serum CTX in OVX rats. CONCLUSION: The present study provides
new insight in preventing estrogen deficiency induced bone loss of SJW and
possibility for its application in bone health supplement.
PMID- 26425275
TI - Protective effects of Artemisia arborescens essential oil on oestroprogestative
treatment induced hepatotoxicity.
AB - BACKGROUND: Currently, natural products have been shown to exhibit interesting
biological and pharmacological activities and are used as chemotherapeutic
agents. The purpose of this study, conducted on Wistar rats, was to evaluate the
beneficial effects of Artemisia arborescens oil on oestroprogestative treatment
induced damage on liver. MATERIALS/METHODS: A total of 36 Wistar rats were
divided into 4 groups; a control group (n = 9), a group of rats who received
oestroprogestative treatment by intraperitoneal injection (n = 9), a group pre
treated with Artemisia arborescens then injected with oestroprogestative
treatment (n = 9), and a group pre-treated with Artemisia arborescens (n = 9). To
minimize the handling stress, animals from each group were sacrificed rapidly by
decapitation. Blood serum was obtained by centrifugation and the livers were
removed, cleaned of fat, and stored at -80C until use. RESULTS: In the current
study, oestroprogestative poisoning resulted in oxidative stress, which was
demonstrated by 1) a significant increase of lipid peroxidation level in hepatic
tissue 2) increased levels of serum transaminases (aspartate amino transferase
and serum alanine amino transferase), alkaline phosphatase, glycemia and
triglycerides and a decrease in the level of cholesterol 3) alteration of hepatic
architecture. Pre-administration of Artemisia arborescens oil was found to
alleviate oestroprogestative treatment induced damage by lowering lipid
peroxidation level and by increasing activity of catalase, superoxide-dismutase,
and glutathione-peroxidase in liver and by reducing disruption of biochemical
parameters. CONCLUSION: Therefore, the results obtained in this study confirmed
that Artemisia essential oil protects against oestroprogestative administration
induced hepatotoxicity by restoration of liver activities.
PMID- 26425276
TI - Sargassum coreanum extract alleviates hyperglycemia and improves insulin
resistance in db/db diabetic mice.
AB - BACKGROUND/OBJECTIVES: The goal of this study was to examine the effect of
Sargassum coreanum extract (SCE) on blood glucose concentration and insulin
resistance in C57BL-KsJ-db/db mice. MATERIALS/METHODS: For 6 weeks, male
C57BL/KsJ-db/db mice were administrated SCE (0.5%, w/w), and rosiglitazone
(0.005%, w/w). RESULTS: A supplement of the SCE for 6 weeks induced a significant
reduction in blood glucose and glycosylated hemoglobin concentrations, and it
improved hyperinsulinemia compared to the diabetic control db/db mice. The
glucokinase activity in the hepatic glucose metabolism increased in the SCE
supplemented db/db mice, while phosphoenolpyruvate carboxykinase and glucose-6
phosphatase activities in the SCE-supplemented db/db mice were significantly
lower than those in the diabetic control db/db mice. The homeostatic index of
insulin resistance was lower in the SCE-supplemented db/db mice than in the
diabetic control db/db mice. CONCLUSIONS: These results suggest that a supplement
of the SCE lowers the blood glucose concentration by altering the hepatic glucose
metabolic enzyme activities and improves insulin resistance.
PMID- 26425278
TI - The effects of Momordica charantia on obesity and lipid profiles of mice fed a
high-fat diet.
AB - BACKGROUND/OBJECTIVES: The present study was conducted to investigate the effects
of dried Momordica charantia aqueous extracts (MCA) and ethanol extracts (MCE) on
obesity and lipid profiles in mice fed a high-fat diet. MATERIALS/METHODS: Forty
two ICR mice were randomly divided into six groups. The normal group was fed a
basal diet, and other groups were fed a 45% high-fat diet (HFD) for 7 weeks. The
normal and HFD groups were also orally administered distilled water each day for
7 weeks. The remaining groups received Momordica charantia extract (0.5 or 1.0
g/kg/day MCA, and 0.5 or 1.0 g/kg/day MCE). In order to measure the anti-obesity
and lipid profile improvement effects, body and visceral tissue weight, lipid
profiles, plasma insulin levels, hepatic malondialdehyde (MDA) levels and
superoxide dismutase (SOD) activity were measured. RESULTS: Both MCA and MCE
significantly decreased body and visceral tissue weight relative to those of the
HFD group (P < 0.05). Additionally high doses of MCE and MCA significantly
reduced the plasmatic insulin levels compared to the HFD groups (P < 0.05) to
concentrations comparable to those found in the normal group. MCA and MCE
supplementation also significantly modulated the lipid profiles in plasma, liver,
and feces compared to mice fed the HFD (P < 0.05). Furthermore MCA and MCE
significantly increased hepatic SOD activity, and reduced MDA generation in the
liver of the HFD mice (P < 0.05). CONCLUSIONS: Results from the present study
suggest that Momordica charantia extracts have anti-obesity effects and the
ability to modulate lipid prolife of mice fed a HFD by suppressing body weight
gain, visceral tissue weight, plasma and hepatic lipid concentrations, and lipid
peroxidation along with increasing lipid metabolism.
PMID- 26425277
TI - Protective role of caffeic acid in an Abeta25-35-induced Alzheimer's disease
model.
AB - BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is characterized by deficits in
memory and cognitive functions. The accumulation of amyloid beta peptide (Abeta)
and oxidative stress in the brain are the most common causes of AD.
MATERIALS/METHODS: Caffeic acid (CA) is an active phenolic compound that has a
variety of pharmacological actions. We studied the protective abilities of CA in
an Abeta25-35-injected AD mouse model. CA was administered at an oral dose of 10
or 50 mg/kg/day for 2 weeks. Behavioral tests including T-maze, object
recognition, and Morris water maze were carried out to assess cognitive
abilities. In addition, lipid peroxidation and nitric oxide (NO) production in
the brain were measured to investigate the protective effect of CA in oxidative
stress. RESULTS: In the T-maze and object recognition tests, novel route
awareness and novel object recognition were improved by oral administration of CA
compared with the Abeta25-35-injected control group. These results indicate that
administration of CA improved spatial cognitive and memory functions. The Morris
water maze test showed that memory function was enhanced by administration of CA.
In addition, CA inhibited lipid peroxidation and NO formation in the liver,
kidney, and brain compared with the Abeta25-35-injected control group. In
particular, CA 50 mg/kg/day showed the stronger protective effect from cognitive
impairment than CA 10 mg/kg/day. CONCLUSIONS: The present results suggest that CA
improves Abeta25-35-induced memory deficits and cognitive impairment through
inhibition of lipid peroxidation and NO production.
PMID- 26425279
TI - Association between fish and shellfish, and omega-3 PUFAs intake and CVD risk
factors in middle-aged female patients with type 2 diabetes.
AB - BACKGROUND/OBJECTIVES: This study was performed to investigate the association
between the dietary intake of fish and shellfish, and omega-3 polyunsaturated
fatty acids (PUFAs) and cardiovascular disease (CVD) risk factors in the middle
aged Korean female patients with Type 2 diabetes (T2D). SUBJECTS/METHODS: A cross
sectional analysis was performed with 356 female patients (means age: 55.5
years), who were recruited from the Huh's Diabetes Clinic in Seoul, Korea between
2005 and 2011. The dietary intake was assessed by a validated semi-quantitative
food frequency questionnaire and analyzed using the Computer Aided Nutritional
Analysis program (CAN-Pro) version 4.0 software. RESULTS: In a multiple
regression analysis after the adjustment for confounding factors such as age,
BMI, duration of diagnosed T2D, alcohol consumption, fiber intake, sodium intake,
and total energy intake, fish and shellfish intake of the subjects was negatively
associated with triglyceride and pulse wave velocity (PWV). Omega-3 PUFAs intake
was negatively associated with triglyceride, systolic blood pressures, diastolic
blood pressures, and PWV. The multiple logistic regression analysis with the
covariates showed a significant inverse relationship between the omega-3 PUFAs
consumption and prevalence of hypertriglyceridemia [OR (95% CI) for greater than
the median compared to less than the median: 0.395 (0.207-0.753)]. CONCLUSIONS:
These results suggest that the consumption of fish and shellfish, good sources of
omega-3 PUFAs, may reduce the risk factors for CVD in the middle-aged female
patients with T2D.
PMID- 26425280
TI - Poor nutrition and alcohol consumption are related to high serum homocysteine
level at post-stroke.
AB - BACKGROUND/OBJECTIVES: Increased serum homocysteine (Hcy) levels have been
reported to be related to the occurrence of cardio- and cerebrovascular diseases.
High serum Hcy levels are also related to the development of secondary stroke and
all-cause mortality. The purpose of this study was to investigate the prevalence
of high serum homocysteine level and relating factors, and the change over the 10
month period post-stroke. SUBJECTS/METHODS: Consecutive stroke patients who were
admitted to the Asan Medical Center were enrolled. Ten months after the onset of
stroke, an interview with a structured questionnaire was performed and blood
samples were obtained for the biochemical parameters. Nutritional status was
determined using the mini nutritional assessment (MNA) score and dietary nutrient
intakes were also obtained using a 24 hour recall method. RESULTS: Out of 203
patients, 84% were malnourished or at risk of malnutrition, and 26% had high
homocysteine levels at 10 months post-stroke. Using logistic regression, the
factors related with high homocysteine levels at 10 months post-stroke included
heavy alcohol consumption (P = 0.020), low MNA scores (P = 0.026), low serum
vitamin B12 (P = 0.021) and low serum folate levels (P = 0.003). Of the 156
patients who had normal homocysteine levels at admission, 36 patients developed
hyperhomocysteinemia 10 months post-stroke, which was related to heavy alcohol
consumption (P = 0.013). Persistent hyperhomocysteinemia, observed in 22 patients
(11%), was related to male sex (P = 0.031), old age (P = 0.042), low vitamin B6
intake (P = 0.029), and heavy alcohol consumption (P = 0.013). CONCLUSION:
Hyperhomocysteinemia is common in post-stroke, and is related to malnutrition,
heavy alcohol drinking and low serum level of folate and vitamin B12. Strategies
to prevent or manage high homocysteine levels should consider these factors.
PMID- 26425281
TI - Evaluation of diet quality and its associated factors among adolescents in Kuala
Lumpur, Malaysia.
AB - BACKGROUND/OBJECTIVES: This study aims to determine contribution of meal
frequency, self-efficacy for healthy eating, and availability of healthy foods
towards diet quality of adolescents in Kuala Lumpur, Malaysia. SUBJECTS/METHODS:
This study was conducted among 373 adolescents aged from 13 to 16 years old. Diet
quality of the respondents was assessed using the Healthy Eating Index for
Malaysians. Meal frequency, self-efficacy for healthy eating, and availability of
healthy foods were assessed through the Eating Behaviours Questionnaire (EBQ),
self-efficacy for healthy eating scale, and availability of healthy foods scale,
respectively. RESULTS: The majority of the respondents (80.7%) were at risk of
poor diet quality. Males (mean = 34.2 +/- 8.2%) had poorer diet quality than
females (mean = 39.9 +/- 9.0%) (t = -5.941, P < 0.05). Malay respondents (mean =
36.9 +/- 8.7%) had poorer diet quality than Indian respondents (mean = 41.3 +/-
10.0%) (F = 2.762, P < 0.05). Age (r = 0.123, P < 0.05), self-efficacy for
healthy eating (r = 0.129, P < 0.05), and availability of healthy foods (r =
0.159, P < 0.05) were positively correlated with the diet quality of the
respondents. However, meal frequency was not correlated with the diet quality of
the respondents. Multiple linear regression analysis showed that being a male,
being a Malay, low self-efficacy for healthy eating, and low availability of
healthy foods contributed significantly towards poor diet quality among
respondents. CONCLUSIONS: In short, sex, ethnicity, self-efficacy for healthy
eating, and availability of healthy foods were associated with diet quality among
adolescents. Health practitioners should take into consideration of differences
in sex and ethnicity during implementation of nutrition-related intervention
programs. Self-efficacy for healthy eating and availability of healthy foods
should be included as important components in improving diet quality of
adolescents.
PMID- 26425282
TI - Attitudes and preferences of consumers toward food allergy labeling practices by
diagnosis of food allergies.
AB - BACKGROUND/OBJECTIVES: The objective of this study was to investigate food
allergens and prevalence rates of food allergies, followed by comparison of
consumer attitudes and preferences regarding food allergy labeling by diagnosis
of food allergies. SUBJECTS/METHODS: A total of 543 individuals living in Seoul
and Gyeonggi area participated in the survey from October 15 to 22 in 2013.
RESULTS: The results show that the prevalence of doctor-diagnosed food allergies
was 17.5%, whereas 6.4% of respondents self-reported food allergies. The most
common allergens of doctor-diagnosed and self-reported food allergy respondents
were peaches (30.3%) and eggs (33.3%), respectively, followed by peanuts, cow's
milk, and crab. Regarding consumer attitudes toward food labeling, checking food
allergens as an item was only significantly different between allergic and non
allergic respondents among all five items (P < 0.001). All respondents reported
that all six items (bold font, font color, box frame, warning statement, front
label, and addition of potential allergens) were necessary for an improved food
allergen labeling system. PLSR analysis determined that the doctor-diagnosed
group and checking of food allergens were positively correlated, whereas the non
allergy group was more concerned with checking product brands. CONCLUSIONS: An
effective food labeling system is very important for health protection of
allergic consumers. Additionally, government agencies must develop policies
regarding prevalence of food allergies in Korea. Based on this information, the
food industry and government agencies should provide clear and accurate food
labeling practices for consumers.
PMID- 26425283
TI - Perceptions and practices of commensality and solo-eating among Korean and
Japanese university students: A cross-cultural analysis.
AB - BACKGROUND/OBJECTIVES: Commensality, eating together with others, is a major
representation of human sociality. In recent time, environments around
commensality have changed significantly due to rapid social changes, and the
decline of commensality is perceived as a serious concern in many modern
societies. This study employs a cross-cultural analysis of university students in
two East Asian countries, and examines cross-cultural variations of perceptions
and actual practices of commensality and solo-eating. SUBJECTS/METHODS: The
analysis was drawn from a free-list survey and a self-administrative
questionnaires of university students in urban Korea and Japan. The free-listing
survey was conducted with a small cohort to explore common images and meanings of
commensality and solo-eating. The self-administrative questionnaire was developed
based on the result of the free-list survey, and conducted with a larger cohort
to examine reasons and problems of practices and associated behaviors and food
intake. RESULTS: We found that Korean subjects tended to show stronger
associations between solo-eating and negative emotions while the Japanese
subjects expressed mixed emotions towards the practice of solo-eating. In the
questionnaire, more Korean students reported they prefer commensality and tend to
eat more quantities when they eat commensally. In contrast, more Japanese
reported that they do not have preference on commensality and there is no notable
difference in food quantities when they eat commensally and alone. Compared to
the general Korean cohort finding, more proportion of overweight and obese groups
of Korean subjects reported that they tend to eat more when they are alone than
normal and underweight groups. This difference was not found in the overweight
Japanese subjects. CONCLUSION: Our study revealed cross-cultural variations of
perceptions and practices of commensality and solo-eating in a non-western
setting.
PMID- 26425284
TI - Nutrition knowledge, outcome expectations, self-efficacy, and eating behaviors by
calcium intake level in Korean female college students.
AB - BACKGROUND/OBJECTIVES: Calcium is important but deficient in diets of young adult
women. This study aimed to examine if cognitive factors and eating behaviors
differ according to calcium intake based on the Social Cognitive Theory.
SUBJECTS/METHODS: Subjects were female college students in Seoul, Korea. Three
hundred students completed the questionnaire regarding calcium intake, nutrition
knowledge, outcome expectations, self-efficacy and eating behaviors. Data on 240
students were analyzed using t-test or chi(2)-test. Subjects were categorized
into two groups, high calcium intake (HC, >= 650 mg/day) and low calcium intake
(LC, < 650 mg/day), according to recommended intakes of calcium for women aged 19
29 years. RESULTS: The LC group constituted 77.9% of total subjects. Nutrition
knowledge was not different according to calcium intake. Three out of 12 outcome
expectations items were significantly different between the HC and LC groups.
Subjects in the HC group agreed more strongly with the practical benefits of
consuming calcium-rich foods, including 'taste' (P < 0.01) and 'going well with
other snacks' (P < 0.05), compared to those in the LC group. Negative
expectations of 'indigestion' were stronger in the LC group than HC group (P <
0.001). Among self-efficacy items, perceived ability of 'eating dairy foods for
snacks' (P < 0.001), 'eating dairy foods every day' (P < 0.01), and 'eating
calcium-rich side dishes at meals' (P < 0.05) differed significantly between the
HC and LC groups. Eating behaviors including more frequent consumption of dairy
foods, fruits or fruit juice (P < 0.001), anchovy, seaweeds, green vegetables,
protein-rich foods (P < 0.05), and less frequent consumption of sweets or soft
drinks (P < 0.01) were significantly related to calcium intake. CONCLUSIONS: This
study found that outcome expectations, self-efficacy in consuming calcium-rich
foods, and eating behaviors are important in explaining calcium intake. Nutrition
education needs to address practical benefits, reduce negative expectations of
calcium-rich foods, increase self-efficacy, and modify eating behaviors
contributing to calcium intake.
PMID- 26425285
TI - Prevalence of osteoporosis according to nutrient and food group intake levels in
Korean postmenopausal women: using the 2010 Korea National Health and Nutrition
Examination Survey Data.
AB - BACKGROUND/OBJECTIVES: Women's bone health status is closely related with
environmental factors and lifestyle factors. The purpose of this study is to
evaluate the dietary risks of osteoporosis and osteopenia for Korean
postmenopausal women. SUBJECTS/METHODS: The data from 1,433 subjects from the
2010 KNHANES were used and divided into three groups: normal, osteopenia, and
osteoporosis group using bone mineral density (BMD). Nutrient intakes and food
intake frequency were evaluated. Logistic regression analysis was applied to
determine the odds ratios for osteoporosis and osteopenia. RESULTS: The RNI
percentage of each nutrient and food intake frequency from 12 food groups
decreased as bone mineral density status deteriorated. Risk for osteoporosis of
low calcium (Ca) intake, under the EAR, showed an odds ratio of 2.13(95% CI; 1.26
3.61, P < 0.05). Higher intake frequency showed preventive effect from
osteoporosis compared to lower intake frequency in such food group as dairy
products (ORs 0.40, CI 0.21-0.75), beans (ORs 0.49, CI 0.29-0.83), seaweeds (ORs
0.55, CI 0.32-0.94), fish (ORs 0.56, CI 0.32-0.98), and fruits (ORs 0.42, CI 0.23
0.79) after adjusting for age. CONCLUSION: To prevent osteoporosis in later life,
sufficient Ca intake and more frequent intakes of foods containing Ca such as
dairy products, beans, fish, seaweeds, and fruits, which help in Ca absorption,
should be stressed for Korean postmenopausal women.
PMID- 26425286
TI - Nutritional status of toddlers and preschoolers according to household income
level: overweight tendency and micronutrient deficiencies.
AB - BACKGROUNDS/OBJECTIVES: The effects of malnutrition on growth of toddlers and
preschoolers by socioeconomic status are not well known. This study aimed to
examine the effects of dietary intake on growth outcomes in toddlers and
preschoolers by household income level. SUBJECTS/METHODS: The study population
was a total of 1,687 children aged 1 to 5 years that participated in the KNHANES
from 2009 to 2011. Growth of children was assessed by height for age (HFA) and
weight for height (WFH). Children were classified into three groups according to
children's HFA and WFH compared to the 10(th) and 90(th) percentiles of the 2007
Korean Children and Adolescent Growth Standard. Average monthly household income
was divided into quartile groups. Dietary intake data were obtained by using the
one day 24-hr recall method. Risks of inadequate intake of nutrients and
unfavorable growth were estimated by using a multiple logistic regression model
adjusted for sex, age, region, and energy intake. RESULTS: The low HFA group (<
10(th) percentile) had significantly lower intakes of energy, carbohydrate, and
thiamin as compared with the high group (>= 90(th) percentile). For WFH status,
vitamin C intake was lower in the low group than in the high group. Household
income level was related to WFH status but not HFA. Children from lower income
households were more likely to have high WFH than those from higher income
households (P for trend = 0.038). Household income status was also significantly
related with risk of inadequate intake of micronutrients such as thiamin (P for
trend = 0.032) and vitamin C (P for trend = 0.002), showing higher odds of
inadequate intakes in children from lower income households. CONCLUSIONS:
Children from lower income households were prone to be overweight and to have
inadequate intakes of micronutrients such as thiamin and vitamin C. To reduce
nutritional and health disparities, collective action in the public sector is
required from early life.
PMID- 26425288
TI - Providing holistic care for older people.
PMID- 26425287
TI - Low consumption of fruits and dairy foods is associated with metabolic syndrome
in Korean adults from outpatient clinics in and near Seoul.
AB - BACKGROUND/OBJECTIVES: The aim of this study was to examine differences in
nutrient intake and food consumption by the presence of metabolic syndrome in
Korean adults. SUBJECTS/METHODS: Study subjects in this cross-sectional study
were recruited from four outpatient clinics in and near the Seoul metropolitan
area of South Korea between 2006 and 2012. A total of 668 subjects (413 men and
255 women) aged >= 30 y were included in the final data analyses. For each
subject, daily nutrient intake and food consumption were calculated using three
days of dietary intake data obtained from a combination of 24-hour recalls and
dietary records. To evaluate food consumption, mean number of servings consumed
per day and percentages of recommended number of servings for six food groups
were calculated. Metabolic syndrome was defined using the National Cholesterol
Education Program Adult Treatment Panel III criteria. The general linear model
was performed to examine differences in nutrient intake and food consumption by
sex and the presence of metabolic syndrome after adjustment for potential
confounding variables. RESULTS: Nutrient intake did not differ by the presence of
metabolic syndrome in both men and women. Men with metabolic syndrome had lower
consumption and percentage of the recommendation for fruits compared with those
without metabolic syndrome (1.6 vs. 1.1 servings/day, P-value = 0.001; 63.5 vs.
49.5%, P-value = 0.013). Women with metabolic syndrome showed lower consumption
and percentage of the recommendation for dairy foods than those without metabolic
syndrome (0.8 vs. 0.5 servings/day, P-value = 0.001; 78.6 vs. 48.9%, P-value =
0.001). CONCLUSIONS: Low intakes of fruits and dairy foods might be associated
with the risk of having metabolic syndrome among Korean adults. Dietary advice on
increasing consumption of these foods is needed to prevent and attenuate the risk
of metabolic syndrome.
PMID- 26425289
TI - Health screening for older people-what are the current recommendations?
AB - The world population of older people is on the rise with improved health
services. With longevity, older people are at increased risk of chronic non
communicable diseases (NCDs), which are also leading causes of death among older
people. Screening through case finding in primary care would allow early
identification of NCDs and its risk factors, which could lead to the reduction of
related complications as well as mortality. However, direct evidence for
screening older people is lacking and the decision to screen for diseases should
be made based on comorbidity, functional status and life expectancy, and has to
be individualised.
PMID- 26425290
TI - Correlation between cognitive impairment and depressive mood of Thai elderly with
type 2 diabetes in a primary care setting.
AB - OBJECTIVE: The objective of this study was to evaluate the relationship between
cognitive impairment and depressive mood in Thai elderly with type 2 diabetes at
primary care centres. MATERIALS AND METHODS: Two-hundred and eighty three (283)
older people with type 2 diabetes were enrolled in this study. Mini-Cog and mini
mental state examination (MMSE) Thai 2002 were used to measure cognitive
impairment while Thai geriatric screening test (TGDS) was used to measure
depressive mood in all participants. Spearmen correlation was applied to
determine the relationship between cognitive function and depressive mood.
RESULTS: There was a positive relationship between cognitive impairment and
depressive mood in older people with type 2 diabetes. The scores from Mini-Cog
and MMSE Thai 2002 were negatively correlated with TGDS scores while adjusting
for the effects of age and years of education with rs = -0.1, p = 0.06 and rs =
0.2, p<0.01, respectively. Although it showed an inverse relationship of the
scores between cognitive and depressive mood screening tests, the results between
the tests were positive when interpreting the test scores. It means that the
higher score in Mini-Cog and MMSE Thai 2002 (non-cognitive impairment) were
associated with the lower score in TGDS (non-depressed mood). CONCLUSION: The
finding of this study showed that older people with type 2 diabetes who had
cognitive impairment seemed to have depressive mood. Hence, these two co
morbidities should be considered in order to give an optimal care to older people
with diabetes.
PMID- 26425291
TI - Poor blood pressure control and its associated factors among older people with
hypertension: A cross-sectional study in six public primary care clinics in
Malaysia.
AB - INTRODUCTION: Hypertension is highly prevalent in the older people. Chronic
disease care is a major burden in the public primary care clinics in Malaysia.
Good blood pressure (BP) control is needed to reduce the morbidity and mortality
of cardiovascular disease (CVD). This study aimed to determine the status of BP
control and its associated factors among older people with hypertension in public
primary care clinics. MATERIALS AND METHODS: A cross-sectional study on
hypertensive patients aged 18 years and above was conducted in six public primary
care clinics in Federal Territory, Malaysia. A total of 1107 patients were
selected via systematic random sampling. Data from 441 (39.8%) patients aged 60
years and more were used in this analysis. BP control was determined from the
average of two BP readings measured twice at an interval of 5 min. For patients
without diabetes, poor BP control was defined as BP of >=140/90 mm Hg and
>=150/90 for the patients aged 80 years and more. For patients with diabetes,
poor control was defined as BP of >=140/80 mm Hg. RESULTS: A total of 51.7% (n =
228) of older patients had poor BP control. The factors associated with BP
control were education level (p = 0.003), presence of comorbidities (p = 0.015),
number of antihypertensive agents (p = 0.001) and number of total medications
used (p = 0.002). Patients with lower education (less than secondary education)
(OR = 1.7, p = 0.008) and the use of three or more antihypertensive agents (OR =
2.0, p = 0.020) were associated with poor BP control. CONCLUSION: Among older
people with hypertension, those having lower education level, or using three or
more antihypertensive agents would require more attention on their BP control.
PMID- 26425292
TI - Management of pulmonary tuberculosis in health clinics in the Gombak district:
How are we doing so far?
AB - This audit report assessed the structure, processes and outcome of the pulmonary
tuberculosis (PTB) management in adults conducted at eight government health
clinics within the high TB burden Gombak district. All newly diagnosed PTB
patients from November 2012 to November 2013 were identified from the
tuberculosis registry. Patients less than 18 years old, were transferred out or
extrapulmonary tuberculosis was excluded from the study. The assessment criteria
for PTB were defined according to the latest Malaysian TB clinical practice
guidelines (TB CPG) 2012. A total of 117 patients were included in this report
and data were extracted and analysed using SPSS version 20.0. The mean age of
patients was 40.4 +/- 14.4 SD. Majority was men (63.2%). Out of 117 patients,
82.1% were Malaysian citizens and 17.9% were foreigners. Malays were the majority
(65%) followed by 7.7% Chinese, 10.3% Indian and 17.1% others. The most common
clinical feature was cough (88.0%) followed by loss of weight (58.1%), loss of
appetite (57.3%), fever (56.4%), night sweat (30.8%) and haemoptysis (32.5%).
Acid-fast bacilli (AFB) smear was positive in 94% of cases. Chest X-ray and human
immunodeficiency virus (HIV) screening results were available for 89.1 and 82.1%
cases respectively. The results for the sputum culture were available in 27.4% of
patients and 54.7% were documented as done but pending results. The clinics have
a successful directly observed therapy (DOT) program with 94.0% patients
documented under DOT. Out of 53 patients on maintenance phase, 47.2% were
identified as cured. Cure rate for those completed treatment was 100%. The
defaulter rate was 17.1%. This audit demonstrated the attempt made by the clinics
to adhere to the recommended guidelines. However, improvements are to be made in
the documentation of medical records, tracing of investigation results and
reduction of the number of defaulters.
PMID- 26425294
TI - A case study of human immunodeficiency virus with positive seroconversion to
negative.
AB - This case study demonstrates a 36-year-old ex-intravenous drug user (IVDU) who
had been initially tested positive for human immunodeficiency virus (HIV) twice
using Enzyme Immunoassay (EIA) method (Particle agglutination, PA done), but a
year later he was tested HIV-negative. The patient was asymptomatic for HIV and T
helper cells (CD4) count remained stable throughout this period. In light of this
case, there may be a need to retest by molecular methods for high risk category
patients who were initially diagnosed HIV-positive, but later showing an
unexpected clinical course, such as a rising or stable CD4 titre over the years.
PMID- 26425295
TI - Night market contact lens-related corneal ulcer: Should we increase public
awareness?
PMID- 26425293
TI - Social support and self-care activities among the elderly patients with diabetes
in Kelantan.
AB - INTRODUCTION: Diabetes is common among the elderly and can significantly affect
their lives including the issues related with social support and diabetic self
care activities. OBJECTIVES: The objective of this study was to examine the
social support and self-care activities among the elderly patients with diabetes.
METHODS: A survey involving 200 patients was conducted from March 2013 to May
2013 in three hospitals in Kelantan. Data were obtained through self-administered
questionnaires and clinical characteristics were acquired from the patients'
records. RESULTS: The scores for social support (mean = 19.26; SD = 2.63) and
self-care activities (mean = 14.83; SD = 4.92) were moderate. Higher social
support was associated with high levels of glycated haemoglobin (HbA1c), fasting
blood sugar (FBS) level, the duration of diabetes and a decrease in body mass
index (BMI) (p<0.05). It was observed that the patients with low educational,
Hb1Ac and FBS level, with other chronic diseases and who have had diabetes for
some time had low self-care activities (p<0.05). There was a significant negative
relationship between an increase in social support and decrease in self-care
activity (p<0.05). CONCLUSION: Healthcare providers, family and friends have to
strengthen their relationship with the elderly patients with diabetes to provide
more social support and promote the compliance with diabetic self-care activities
to improve clinical outcomes.
PMID- 26425296
TI - A boy with bluish neck swelling on screaming.
PMID- 26425297
TI - A boy with blue sclera and recurrent fractures.
PMID- 26425298
TI - The challenging task of gatekeeping.
PMID- 26425299
TI - Factors influencing the role of primary care providers as gatekeepers in the
Malaysian public healthcare system.
AB - Primary care providers play an important gatekeeping role in ensuring appropriate
referrals to secondary care facilities. This cross-sectional study aimed to
determine the level, pattern and rate of referrals from health clinics to
hospitals in the public sector, and whether the placement of resident family
medicine specialist (FMS) had made a significant difference. The study was
carried out between March and April in 2012, involving 28 public primary care
clinics. It showed that the average referral rate was 1.56% for clinics with
resident FMS and 1.94% for those without resident FMS, but it was not
statistically significant. Majority of referred cases were considered appropriate
(96.1%). Results of the multivariate analysis showed that no prior consultation
with senior healthcare provider and illnesses that were not severe and complex
were independently associated with inappropriate referrals. Severity, complexity
or uncertain diagnosis of patients' illness or injury significantly contributed
to unavoidable referrals. Adequate facilities or having more experienced doctors
could have avoided 14.5% of the referrals. The low referral rate and very high
level of appropriate referrals could indicate that primary care providers in the
public sector played an effective role as gatekeepers in the Malaysian public
healthcare system.
PMID- 26425300
TI - Prevalence, awareness, treatment and control of diabetes mellitus among the
elderly: The 2011 National Health and Morbidity Survey, Malaysia.
AB - Diabetes mellitus is an important cardiovascular risk factor. The objective of
this study was to provide population-based estimates on the prevalence,
awareness, treatment and control rate of diabetes among the older persons in
Malaysia. Analysis of secondary data from a cross-sectional national population
based survey was done, which was conducted in 2011 throughout Malaysia. A total
of 2764 respondents (15.5%) were older persons. The overall prevalence of
diabetes among older persons was 34.4% in which 65.2% were aware of their
diabetes status. Out of those who were aware, 87.5% had been treated. Only 21.8%
of those treated had their diabetes controlled. The results of multiple logistic
regression showed that the factors associated with higher awareness rates were
women, Indians and higher income groups; factors associated with higher treatment
rates were urban residents and those who were married and widow/widower/
divorcee. There was a high overall prevalence, awareness and treatment rate of
diabetes among older persons in Malaysia but with suboptimal control rate.
PMID- 26425301
TI - Risk factors for women attending pre-pregnancy screening in selected clinics in
Selangor.
AB - BACKGROUND: The Ministry of Health is committed to achieve Millenium Development
Goal (MDG) MDG 4 and 5 by 2015 and include pre-pregnancy care as a strategy. This
study evaluates the risk factors detected during the pre-pregnancy screening at
selected public primary care clinics in Selangor. OBJECTIVES: The objectives of
this study were to determine the proportion of women with risk factors receiving
pre-pregnancy care in selected clinics in Selangor, their socio demographic
features, the types of risk factors detected and their significance. METHODS: A
retrospective review using secondary data was carried out from the month of March
until June 2013 in four public primary care clinics in Klang and Petaling
districts of Selangor. Data were obtained through non-probability sampling, using
the pre-pregnancy screening form utilised in 2012, which is a standard
questionnaire to determine the presence of risk factors. Women with at least one
defined risk factor were considered as being at risk of an adverse obstetric
outcome. Data were analysed using SPSS version 16. RESULTS: A total of 840 pre
pregnancy screening forms were collected. However only 614 (73.1%) were analysed
and studied. The proportion of women with at least one risk factor was 68.8% (95%
CI: 65.1, 72.5). The majority was Malays who had tertiary education and earned
more than RM 1000. Most were in the reproductive age group of 18-35 years old
(350, 82.9%). The mean age was 28.68 + 5.78 years. Most of the women were parous
(259, 65.1%) and did not practice any form of contraception (308, 80.8%) despite
having risks. The percentage of those not receiving any form of immunisation was
small i.e. 9.8% but it was of importance and needed to be addressed prior to the
conception. This study did not reveal any person with mental disorder or those
who endured domestic abuse. Additionally, 3% (12) of them had unhealthy lifestyle
habits, which include smoking, alcohol and substance abuse. Approximately one
third (212, 35.2%) of the women screened were overweight and obese, putting them
at risk of developing gestational diabetes mellitus, pregnancy induced
hypertension or deep vein thrombosis. The mean body mass index (BMI) for those at
risk was 25.36 + 5.94 compared to 21.06 +/- 1.46 for those with no risk. This
study also found a small percentage of women with raised blood pressure (3.9%),
abnormal physical examination (1.5%) and anaemia (14.4%), which need to be
investigated and treated prior to conception. CONCLUSION: More than half of the
women who attended the pre-pregnancy screening were found to have at least one
risk factor.
PMID- 26425302
TI - Low vision rehabilitation and ocular problems among industrial workers in a
developing country.
AB - AIM: Work-related ocular injuries and illnesses were among the major causes of
job absenteeism. This study was conducted to determine if low vision
rehabilitation was provided following work-related ocular problems among
industrial workers in a developing country. This was a retrospective analysis of
case records. METHOD: Randomly selected records of all employees from the Social
Security Organization (SOCSO) Medical Board for 2004 who suffered from ocular
injuries and illnesses were selected. Rates of ocular injuries and illnesses
according to age, gender, races, types of injuries, types of industries, visual
rehabilitation and types of medical interventions were tabulated and analysed.
RESULTS: A total of 26 cases of ocular injuries and illnesses were identified
where 46.2% suffered from ocular injuries. The remaining 53.8% had ocular and/or
systemic diseases. The 40-49-yearold age group suffered the greatest number of
injuries (26.92%). Ocular perforating injuries (66.67%) and ocular contusions
(33.33%) were the most common types of ocular injury among industrial workers in
Kuala Lumpur. Most injuries occurred among workers in the service industry (50%).
Almost 60% of these injured workers did not receive any low vision rehabilitation
after medical intervention while 25% were given contact lenses or spectacles as
rehabilitation and remaining had surgery. CONCLUSION: The low vision
rehabilitation is still unexplored in the management of ocular injuries and
illnesses among industrial workers. Introducing low vision rehabilitation can
benefit both workers and employers as it provides care beyond spectacles or
contact lens prescriptions.
PMID- 26425303
TI - Tuberculosis in adults.
AB - Tuberculosis (TB) in Malaysia is rising due to multiple factors and issues
related to its management are addressed in the updated evidence-based clinical
practice guidelines. Screening for active TB should be considered in high risk
groups. Light emitting diode-based fluorescence microscopy and nucleic acid
amplification tests are recommended investigations. Health education and
standardised 6-month daily antituberculosis (antiTB) regimen are among important
elements for successful treatment. Latent TB infection screening should only be
performed on high risk individuals. AntiTB regimen offered to HIV-positive adults
should be the same as for HIV-negative adults and timing to initiate highly
active antiretroviral therapy in patients with TB is based on CD4 count. All
patients on antiTB treatment should be monitored to assess their response to
treatment and to identify problems associated with it.
PMID- 26425304
TI - Isolation of Mycobacterium fortuitum in sputum specimens of a patient with
chronic cough: Is it clinically significant?
AB - Managing chronic cough is diagnostically challenging especially in primary care.
This case report highlights the difficulties experienced in approaching a case of
chronic cough from a primary care perspective. The discussion also involves the
clinical significance and treatment dilemma of M. fortuitum chelonae complex that
was isolated from the sputum cultures of an elderly woman who presented with
chronic cough for more than a year.
PMID- 26425305
TI - Full thickness macular hole: Early intervention is an important factor in visual
prognosis.
AB - Full thickness macular hole is an eye disease, which can cause permanent visual
impairment. Current advancement in vitreoretinal surgery has high success rates
in repairing them, leading to a significant visual improvement, especially if
patient presents early. In this article, three cases of idiopathic full thickness
macular hole with different visual outcomes have been presented. All cases were
referred by the primary care practitioners and had undergone macular hole surgery
with the same vitreoretinal surgeon. The visual outcome was best in the patient
who had the earliest presentation and referral. Early detection and referral of
these patients is vital so that early surgical intervention can be carried out to
improve their vision.
PMID- 26425306
TI - An intravenous drug abuser with painless neck masses.
PMID- 26425307
TI - Common Molecular Challenges in Glaucoma.
PMID- 26425308
TI - Conjunctival Lesions; a Histopathologic Review in Fars Province, Iran.
AB - PURPOSE: To determine the prevalence of various types of conjunctival lesions, at
a tertiary ophthalmic center in Fars Province, South of Iran. METHODS:
Histopathologic slides and medical records of conjunctival lesions submitted to
the pathology department of Khalili Hospital, Shiraz, Iran were reviewed from
April, 2009 to July, 2013. The histopathologic diagnoses were categorized into
benign, pre-malignant, and malignant lesions. The prevalence of various types of
conjunctival lesions was calculated. RESULTS: Histologic sections of 631
conjunctival lesions were reviewed. Benign lesions were most prevalent (81.8%),
followed by premalignant (10.8%) and malignant (7.4%) lesions. Pterygia were the
most common benign lesions (69.2%), intraepithelial dysplasia constituted most
cases of premalignant lesions (94.1%), and squamous cell carcinoma was the most
frequent malignant lesion (93.6%). Benign lesions were the most common type of
lesions in all age groups, however the prevalence of malignant lesions increased
significantly with age (P < 0.001). CONCLUSION: Benign lesions were the most
common conjunctival lesions with pterygia on top of the list, while
intraepithelial neoplasia and squamous cell carcinoma were the most common
premalignant and malignant lesions, respectively. Conjunctival malignant lesions
were more prevalent with older age.
PMID- 26425309
TI - Is Corneal Sensitivity Sex Dependent?
AB - PURPOSE: To determine whether corneal sensitivity is different between the two
genders. METHODS: Corneal sensitivity of 130 normal volunteers, including 77
women and 53 men aged 20-35 years, with no history of previous ocular surgery was
measured using the Cochet-Bonnet esthesiometer. Measurements were done on five
corneal regions: central, nasal, inferior, temporal and superior. The findings
were compared between men and women using the non-parametric Mann-Whitney U test.
RESULTS: Mean age of male subjects was 28.0 years and that of female participants
was 26.8 years (P = 0.063). There was a significant difference in corneal
sensitivity between men and women in the superior (P = 0.013), temporal (P =
0.020) and inferior (P = 0.046) regions. There was no significant difference in
corneal sensitivity in the central (P = 0.862) and nasal (P = 0.273) regions.
CONCLUSION: Except for the central and nasal regions, corneal sensitivity is
significantly higher in men as compared to women. The reason for this difference
is not yet evident.
PMID- 26425310
TI - Chlorhexidine Monotherapy with Adjunctive Topical Corticosteroids for
Acanthamoeba Keratitis.
AB - PURPOSE: To assess the efficacy of chlorhexidine monotherapy for Acanthamoeba
keratitis, and to determine the therapeutic outcomes of concomitant topical
corticosteroids. METHODS: In this prospective interventional case series, 31 eyes
of 31 patients with Acanthamoeba keratitis (AK) were treated with chlorhexidine
0.02% as monotherapy, from April 2010 to April 2011. The diagnosis of AK was made
based on clinical manifestations and positive confocal microscopic (confoscan
3.4, Nidek Co. Ltd., Gamagori, Japan) results. We report the percentage of a
favorable clinical response within two weeks of initiating treatment, worsening
of the infection while receiving chlorhexidine, recovery of visual acuity (VA),
duration of treatment with chlorhexidine and corticosteroids, necessity for
addition of other anti-Acanthamoeba agents, presence of corneal scar at the end
of the treatment, and need for penetrating keratoplasty (PK). RESULTS: Two weeks
after initiation of chlorhexidine, improvement in signs and symptoms was observed
in 26 (83.9%) patients but 3 eyes required the addition of propamidine. After
initial improvement in one patient, the infection worsened, necessitating the
addition of Polyhexamethylene Biguanide (PHMB) and propamidine. A total of 26
(83.9%) patients received topical corticosteroids with mean duration of 65.8 +/-
45.1 days. In 22 (71%) eyes, final visual acuity was >=0.80. Improved VA occurred
in 29 eyes (93.5%). Optical PK was considered in 3 (9.7%) eyes and a corneal scar
developed in 8 (25.8%) eyes. CONCLUSION: Chlorhexidine is effective for
monotherapy in AK and could be a good choice for initiating treatment. After the
initial response to anti-Acanthamoeba agents, corticosteroids can be used as
adjunctive therapy depending on the clinical condition.
PMID- 26425311
TI - Deep Anterior Lamellar Keratoplasty in Keratoconic Patients with versus without
Vernal Keratoconjunctivitis.
AB - PURPOSE: To compare the clinical outcomes of deep anterior lamellar keratoplasty
(DALK) for keratoconus in patients with vernal keratoconjunctivitis (VKC) versus
those without VKC. METHODS: In this retrospective comparative study, records of
262 eyes with keratoconus (Group 1) and 28 keratoconic eyes with VKC (Group 2)
that had undergone DALK were compiled. Reviewed parameters included length of
follow-up, best-corrected visual acuity (BCVA), refractive error, complications
and cumulative graft survival. RESULTS: Mean duration of follow-up was 38.6 +/-
20.2 and 34.4 +/- 20.9 months in groups 1 and 2, respectively (P = 0.21). Mean
post-operative BCVA was 0.19 +/- 0.11 and 0.20 +/- 0.15 logMAR, in groups 1 and 2
(P = 0.79). BCVA>=20/40 was achieved in 91.6 and 88.5% of eyes in groups 1 and 2,
respectively (P = 0.48). Epithelial problems were encountered in 31.3 and 42.9%
of operated eyes, respectively (P = 0.16). Vascularization of suture tracts and
stitch abscesses were encountered more frequently in the eyes with VKC (P = 0.01
and <0.001, respectively). At the 33-month follow-up examination, rejection-free
graft survival rates were 56.0% in group 1 and 33.3% in group 2, with mean
durations of 41.0 and 32.1 months, respectively (P = 0.15). Graft survival rates
were 98.1% in group 1 and 95.0% in group 2, with mean durations of 88.6 and 88.4
months, respectively (P = 0.74). CONCLUSION: Clinical outcomes of DALK in
keratoconic eyes with VKC were comparable to those in eyes with keratoconus
alone. However, complications such as suture tract vascularization and stitch
abscesses were more common when VKC coexisted, necessitating closer monitoring.
PMID- 26425312
TI - Lens Densitometry after Corneal Cross-linking in Patients with Keratoconus Using
a Scheimpflug Camera.
AB - PURPOSE: To evaluate changes in crystalline lens densitometry following corneal
cross-linking (CXL) in keratoconic patients. METHODS: In a quasi-experimental
study, three-dimensional lens densitometry was performed using the Pentacam
Scheimpflug camera (Oculus Optikgerate GmbH, Wetzlar, Germany) at baseline and
six months after CXL. Densitometry was performed in a fixed area of 2 inch * 1
inch of the anterior capsule and anterior lens cortex. The subject group included
patients with progressive keratoconus who underwent CXL (n = 40) and the control
group was comprised of aged-matched patients with non-progressive keratoconus (n
= 36). RESULTS: Mean age of the case and control groups was 25.8 +/- 4.0 and 25.0
+/- 4.1 years, respectively (P = 0.392). Mean lens density in the CXL group was
6.68% +/- 0.58% at baseline and 6.77% +/- 0.53% at the last visit (P = 0.352).
Corresponding figures in the control group were 6.53% +/- 0.27% and 6.39% +/-
0.31%, respectively (P = 0.213). There was no significant difference between the
study groups at baseline or six months later (P = 0.96). CONCLUSION: In this
short term study with six months' follow-up, we observed no significant impact on
lens density following exposure of the crystalline lens to ultraviolet A and
riboflavin free radicals in the CXL procedure.
PMID- 26425314
TI - Prevalence of Color Vision Deficiency and its Correlation with Amblyopia and
Refractive Errors among Primary School Children.
AB - PURPOSE: To determine the prevalence of color vision deficiency (CVD) and its
correlation with amblyopia and refractive errors among primary school children.
METHODS: In this population-based cross-sectional study, 2160 children were
selected from 36 primary schools; 60 students were from each school (10 students
in each grade), with equal sex distribution. A complete eye examination including
refraction using a photorefractometer, determination of visual acuity (VA) and
color vision using a Yang vision tester, and evaluation of ocular media opacity
using a direct ophthalmoscope was performed. Children who could not answer at
least 4 plates of the Ishihara color test were considered as color vision
deficient subjects. Amblyopia was determined if pinhole VA was worse than 0.3
LogMAR (equal to 20/40). RESULTS: The prevalence of CVD was 2.2% (95% CI: 1.5% to
3%) which was higher in male subjects (37 [3.5%] boys vs. 11 [1.0%] girls, P <
0.001). Mean VA was lower among students with CVD as compared to normal color
vision children (P = 0.035) and amblyopia was observed in 8.3% (95% CI: 0.2% to
16.4%) of patients with CVD versus 2.1% (95% CI: 1.5% to 2.08%) of children with
normal color vision perception (P = 0.005). A statistically significant
correlation between lower VA and CVD was observed (P = 0.023). CONCLUSION:
Although CVD was correlated with lower VA and amblyopia, there was no
relationship between CVD and the type of amblyopia, refractive error,
anisometropia or strabismus.
PMID- 26425313
TI - A Possible Role for LTBP2 in the Etiology of Primary Angle Closure Glaucoma.
AB - PURPOSE: To assess the association of LTBP2 mutations with primary angle closure
glaucoma (PACG). METHODS: We studied 54 unrelated patients with PACG and one
individual with pseudoexfoliation accompanied with angle closure glaucoma; these
consisted of 28 female and 27 male subjects aged 27 to 82 (mean, 63) years. The
36 exons and flanking intronic sequences of LTBP2 in all patients were amplified
by PCR and sequenced by the Sanger protocol. The sequences were compared to LTBP2
reference sequences. A total of 100 to 400 controls aged at least 60 years old
were screened for various variations. RESULTS: Out of 24 observed sequence
variations, ten were in amino acid coding regions; of these four created
synonymous codons while six caused amino acid changes. Based on allele
frequencies, biochemical parameters, absence in control individuals, evolutionary
conservation of affected amino acids, and bioinformatic predictions on the
effects on protein function, it was concluded that only two mutations causing p.
Gln1417Arg and p. Gly1660Trp may contribute to PACG. The p. Gly1660Trp mutation
was observed in a patient with both PACG and PEX syndrome. P. Gln1417Arg had
previously been reported only in a subject with POAG. CONCLUSION: LTBP2 may
contribute to PACG. This finding emphasizes that there may be an overlap in the
etiology of various forms of glaucoma and the overlaps likely contribute to
common features in various forms of glaucoma.
PMID- 26425315
TI - Bilateral Vitreous Hemorrhage in Children: Clinical Features and Outcomes.
AB - PURPOSE: To determine the etiology, clinical features and outcomes of bilateral
vitreous hemorrhage (VH) in children. METHODS: This retrospective chart review
was performed on patients with bilateral VH under the age of 18 at a tertiary eye
care center in India. Data included demographics, details of history and ocular
examination, reports of investigations, surgeries or other interventions
performed, and final anatomical and visual outcomes. Patients were divided into
two groups i.e., traumatic and non-traumatic (spontaneous). RESULTS: The
traumatic group was comprised of 37 patients including 27 male and 10 female
subjects with mean age of 13.47 +/- 5.31 years, the most common complaint was
decreased vision (96.45%) and the most prevalent etiology was firecracker injury
in 16 (43.2%) patients. Mean baseline visual acuity (VA) was 2.34 +/- 1.31 logMAR
which was significantly improved to 1.08 +/- 0.23 logMAR (P = 0.042). The mean
number of surgeries was 2.72 +/- 1.43 in the traumatic VH and mean follow up
period was 23.14 +/- 6.54 months. The spontaneous group included 48 subjects
comprised of 27 male and 21 female cases with mean age of 14.48 +/- 2.03 years.
The most common cause was vasculitis in 21 (43.75%) subjects including four
patients with tuberculosis. Mean baseline VA was 1.97 +/- 1.13 logMAR which
showed a significant improvement to 0.82 +/- 0.24 logMAR (P = 0.012) after mean
follow up of 34.2 +/- 11.2 months. Eleven patients required at least one major
surgery. CONCLUSION: Vasculitis was the most common cause of spontaneous
bilateral VH; traumatic VH most prevalently occurred due to firecracker injury.
Final VA was better in the spontaneous group.
PMID- 26425316
TI - Effect of Monocular Deprivation on Rabbit Neural Retinal Cell Densities.
AB - PURPOSE: To describe the effect of monocular deprivation on densities of neural
retinal cells in rabbits. METHODS: Thirty rabbits, comprised of 18 subject and 12
control animals, were included and monocular deprivation was achieved through
unilateral lid suturing in all subject animals. The rabbits were observed for
three weeks. At the end of each week, 6 experimental and 3 control animals were
euthanized, their retinas was harvested and processed for light microscopy.
Photomicrographs of the retina were taken and imported into FIJI software for
analysis. RESULTS: Neural retinal cell densities of deprived eyes were reduced
along with increasing period of deprivation. The percentage of reductions were
60.9% (P < 0.001), 41.6% (P = 0.003), and 18.9% (P = 0.326) for ganglion, inner
nuclear, and outer nuclear cells, respectively. In non-deprived eyes, cell
densities in contrast were increased by 116% (P < 0.001), 52% (P < 0.001) and
59.6% (P < 0.001) in ganglion, inner nuclear, and outer nuclear cells,
respectively. CONCLUSION: In this rabbit model, monocular deprivation resulted in
activity-dependent changes in cell densities of the neural retina in favour of
the non-deprived eye along with reduced cell densities in the deprived eye.
PMID- 26425317
TI - Endothelin-1 and Nitric Oxide Levels in Exudative Age-Related Macular
Degeneration.
AB - PURPOSE: To evaluate plasma levels of endothelin-1 (ET-1) and nitric oxide (NO)
in patients with exudative age-related macular degeneration (AMD). METHODS: In
this study, ET-1 levels, as well as nitrite plus nitrate concentrations as an
indicator of plasma NO level, were measured in the plasma of 20 subjects with
exudative AMD and compared with 20 healthy age and sex matched controls. RESULTS:
Mean plasma ET-1 level was significantly higher in exudative AMD patients as
compared to control subjects (0.35 +/- 0.06 fmol/ml versus 0.17 +/- 0.03 fmol/ml,
P = 0.015). Patients with exudative AMD also showed significantly lower mean
plasma levels of nitrite plus nitrate as compared to the controls (58.9 +/- 2.7
umol/l versus 82.6 +/- 5.9 umol/l, P = 0.001). CONCLUSION: Increased
concentrations of ET-1 and reduced levels of NO in the plasma may suggest an
imbalance between vasoconstrictor and vasodilator agents, respectively, as a
reflection of endothelial dysfunction in the pathogenesis of AMD. These findings
may also imply the role of vasoconstriction in exudative AMD.
PMID- 26425318
TI - Tumor Necrosis Factor Gene Polymorphisms in Advanced Non-exudative Age-related
Macular Degeneration.
AB - PURPOSE: To investigate tumor necrosis factor (TNF)-alpha gene polymorphisms in
advanced dry-type age-related macular degeneration (AMD) in a population from
Northeastern Iran. METHODS: In this case-control study, 50 patients with
geographic macular atrophy and 73 gender-matched controls were enrolled. Genomic
deoxyribonucleic acid (DNA) was extracted from the peripheral blood. Polymerase
chain reaction was performed to analyze 2 candidate single nucleotide
polymorphisms in the TNF-alpha gene, namely -1031 thymine (T)/cytosine (C) and
308 guanine (G)/adenine (A). RESULTS: The distribution of the - 1031 T/C genotype
was TT, 62%; TC, 36%; CC, 2% in the patients and TT, 60%; TC, 36%; CC, 4% in the
controls (P = 0.94). Genotype analysis of TNF-alpha -308 also revealed no
significant difference in distribution between patients (G, 78%; GA, 22%; AA, 0%)
and controls (GG, 74%; GA, 23%; AA, 3%) (P = 0.51). None of the haplotypes nor
alleles of studied TNF-alpha polymorphisms were significantly associated with
advanced dry-type AMD. CONCLUSION: The findings of this study show that
polymorphisms in the TNF-alpha gene, do not play an important role in dry-type
AMD in the studied population.
PMID- 26425319
TI - Retinal Sensitivity over Hard Exudates in Diabetic Retinopathy.
AB - PURPOSE: To evaluate retinal sensitivity over hard exudates in correlation with
the spectral domain optical coherence tomography (SD-OCT) findings in eyes with
diabetic retinopathy. METHODS: Twelve eyes of 10 patients with hard exudates
associated with diabetic retinopathy were enrolled in this study. All subjects
underwent a complete ophthalmic examination including SD-OCT (Copernicus,
Zawiercie, Poland) and microperimetry (MP1; Nidek Technologies, Padova, Italy).
Retinal sensitivity was measured, over the areas with hard exudates and compared
to corresponding locations devoid of hard exudates, using a semi-automatic
program. The size of the hard exudate plaque was measured using the measurement
software in the microperimeter. Retinal thickness in the area of the hard
exudates and foveal thickness were measured using SD-OCT. RESULTS: Mean retinal
sensitivity over hard exudates was 4.97 +/- 4.17 dB which was significantly (P =
0.0001) reduced as compared to locations devoid of hard exudates. No significant
correlation (r=-0.23, P = 0.45) was found between the size of the hard exudates
and retinal sensitivity. A significant negative correlation was found between
retinal sensitivity and retinal thickness at the area of the hard exudates (r=
0.65, P = 0.05), and between retinal sensitivity and foveal thickness (r=-0.91, P
= 0.001). CONCLUSION: In eyes with diabetic retinopathy, retinal sensitivity was
reduced due to the presence of hard exudates in the outer retinal layers and
retinal thickening but this was not correlated with the size of the hard
exudates.
PMID- 26425320
TI - Multifocal Electroretinogram in Diabetic Macular Edema; Correlation with Visual
Acuity and Optical Coherence Tomography.
AB - PURPOSE: To evaluate multifocal electroretinogram (mfERG) changes in eyes with
diabetic macular edema (DME) and investigate any possible correlation with
optical coherence tomography (OCT) features and visual acuity (VA). METHODS:
Twenty-nine right eyes of 29 subjects with DME due to non-proliferative diabetic
retinopathy and 30 eyes of 30 normal subjects were evaluated. All patients
underwent a complete ophthalmic examination. Sixty-one scaled hexagon mfERG
responses were recorded. Components of the first order kernel of N1, N2, and P1
in five concentric rings centered on the fovea, were measured in both groups.
Correlation and regression analyses were performed among VA, central macular
thickness (CMT) based on OCT, mfERG amplitude, and latency of the N1, N2 and P1
waves. RESULTS: Significant differences were observed in all mfERG parameters in
five-ring regions of the retina between eyes with DME versus controls (P < 0.05).
There were significant correlations among VA with N2 (P = 0,001, b = 0.73) and P1
amplitudes (P = 0.001, b = -0.84) in the central macular area, and there was a
borderline association between VA and CMT (P = 0.042, b = 0.392). CONCLUSION:
Amplitudes of mfERG components (N1, P1, and N2) are significantly reduced and
their latencies are delayed in eyes with DME indicating functional impairment in
the outer retina. The mfERG total amplitude was significantly correlated with VA
even more than CMT, therefore the combined use of OCT and mfERG for macular
evaluation may better evaluate visual status in DME patients.
PMID- 26425321
TI - Foveal Structure in Macula-off Rhegmatogenous Retinal Detachment after Scleral
Buckling or Vitrectomy.
AB - PURPOSE: To evaluate foveal microstructural changes and to determine its
association with visual outcomes after reattachment of rhegmatogenous retinal
detachments (RRDs) by scleral buckling (SB) or pars plana vitrectomy (PPV).
METHODS: Using spectral domain optical coherence tomography (SD-OCT), foveal
microstructure in eyes with macula-off RRD were studied 1, 3, 6, 9, 12 and 15
months after PPV or SB and correlated with visual outcomes. RESULTS: Forty-two
eyes were included in the final analysis. Even with improved microstructural
changes and normalization of retinal structures on OCT, final visual acuity was
not correlated with microstructural changes in eyes undergoing PPV. In the SB
group, final visual acuity was significantly correlated with an intact inner
segment/outer segment (IS/OS) junction (P = 0.013). There was no significant
correlation between final visual acuity and presence of subretinal fluid (SRF) in
either group. CONCLUSION: After SB, eyes with an intact IS/OS junction had better
final visual acuity. In the PPV group, there was no significant correlation
between microstructural changes and visual acuity. The presence of SRF did not
influence final visual acuity in both groups.
PMID- 26425322
TI - Senile Dementia and Glaucoma: Evidence for a Common Link.
AB - Dementia and glaucoma are both neurodegenerative conditions characterized by
neuronal loss leading to cognitive and visual dysfunction, respectively. A
variety of evidence exists linking the two diseases including structural signs,
specifically degenerative changes within ganglion cells. Both diseases become
more prevalent with increased age, but that alone is unlikely to account for the
increased co-prevalence of the diseases found in various studies. Neurotoxic
substances including abnormal hyperphosphorylated tau and amyloid-beta have been
found in both disease processes suggesting possible pathophysiologic links
between the diseases. The exact mechanism of apoptosis, whether by direct
toxicity or potentiation, still needs to be established, but could prove
important for both diseases. Another potential link relates to low intracranial
pressure in patients with both diseases causing a high translaminar pressure
gradient and optic nerve damage in certain patients. While this alone may not
account for direct optic nerve damage, it could lead to cerebrospinal fluid (CSF)
circulatory failure causing increased neurotoxins along the optic nerves with
resultant damage. All of this evidence suggests the need to further study links
between the two diseases, as this could prove instrumental in understanding their
overlapping pathophysiology and developing directed therapies for both diseases.
While this is more thoroughly investigated, it may be prudent to have a lower
threshold for a glaucoma work-up in patients with pre-existing dementia.
PMID- 26425323
TI - Herpes Simplex Virus Endotheliitis following Descemet's Membrane Endothelial
Keratoplasty.
AB - PURPOSE: To report a case of herpes simplex virus (HSV) endotheliitis following
simultaneous phacoemulsification, intraocular lens (IOL) implantation and
descemet's membrane endothelial keratoplasty (DMEK). CASE REPORT: A;45 year-old
female with corneal endothelial decompensation and a mature cataract, and history
of anterior uveitis underwent simultaneous phacoemulsification, IOL implantation
and DMEK. Increased corneal edema and descemet's membrane (DM) detachment
occurred on postoperative day 3 and 5, respectively. One week after surgery,
active keratic precipitates (KPs) appeared. Polymerase chain reaction (PCR)
analysis was performed on an aqueous sample which was positive for herpes simplex
virus (HSV). After initiating oral acyclovir and frequent topical
corticosteroids, the corneal edema resolved and the donor tissue became
spontaneously reattached to the recipient corneal stroma. CONCLUSION: HSV
endotheliitis may occur in the early postoperative period after DMEK and manifest
as endothelial dysfunction leading to donor detachment. Anti-viral medication may
help treat the acute phase and reduce the risk of recurrence.
PMID- 26425325
TI - Optical Coherence Tomography Features in Idiopathic Retinal Vasculitis, Aneurysms
and Neuroretinitis Syndrome.
PMID- 26425324
TI - Optic Nerve Aplasia: Case Report and Literature Review.
AB - PURPOSE: To report three cases of optic nerve aplasia (ONA). CASE REPORT: Herein
three subjects with ONA are described, two subjects had unilateral involvement.
In one of these cases, the fellow eye had an associated persistent hyperplastic
primary vitreous (PHPV). The third patient had bilateral ONA with multiple
intracranial anomalies. Previous reports are reviewed and reported findings are
summarized. Orbital and brain magnetic resonance imaging (MRI) were normal in two
of our cases and loss of corpus callosum in the third case. Narrow optic nerve
was observed on the right side and normal appearance in other two patients.
CONCLUSION: The diagnosis of optic nerve abnormalities in children requires a
thorough ophthalmic examination and proper ancillary testing. Although MRI is
valuable in the diagnosis of associated central nervous system anomalies, the
optic nerve may appear in normal size and course on MRI images and thus one may
not be able to diagnose ONA in eyes with opaque media.
PMID- 26425326
TI - Multimodal Imaging of Posterior Dislocation of Crystalline Lens Nucleus following
Vitrectomy.
PMID- 26425327
TI - Public Health Interventions to Reduce the Prevalence of Blindness in Developing
Countries.
PMID- 26425328
TI - Erratum: Central Corneal Thickness in Highly Myopic Eyes: Interdevice Agreement
of Ultrasonic Pachymetry, Pentacam and Orbscan II Before and After
Photorefractive Keratectomy: Erratum.
AB - [This corrects the article on p. 14 in vol. 9, PMID: 24982727.].
PMID- 26425329
TI - Quit Smoking Experts' Opinions toward Quality and Results of Quit Smoking Methods
Provided in Tobacco Cessation Services Centers in Iran.
AB - BACKGROUND: One of the core responsibilities of health system is to treat tobacco
dependence. This treatment includes different methods such as simple medical
consultation, medication, and telephone counseling. To assess physicians'
opinions towards quality and result of different quit smoking methods provided in
tobacco cessation services centers in Iran. METHODS: In this cross-sectional and
descriptive study, random sampling of all quit centers at country level was used
to obtain a representative sample size of 100 physicians. Physicians completed a
self-administered questionnaire which contained 10 questions regarding the
quality, cost, effect, side effects, and the results of quitting methods using a
5-point Likert-type scale. Percentages, frequencies, mean, T-test, and variance
analyses were computed for all study variables. RESULTS: Most experts preferred
to use combination quit smoking methods and then Nicotine Replacement Therapy
(NRT) with 26 and 23, respectively. The least used methods were quit line and
some methods without medication with 3 cases. The method which gained the maximum
scores were telephone consultation, acupuncture, Willpower, Champix, combined
method, and Interactive Voice Response (IVR) with the mean of 23.3, 23, 22.5, 22,
21.7 and 21.3, respectively. The minimum scores were related to e-cigarette, some
methods without medication, and non-NRT medication with the mean of 12.3, 15.8
and 16.2, respectively. There were no significant differences in the mean of
scores based on different cities (P = 0.256). Analysis of variance in mean scores
showed significant differences in the means scores of different methods (P <
0.000). CONCLUSIONS: According to physicians acupuncture, personal methods and
Champix are the most effective methods and these methods could be much more
feasible and cost effective than other methods.
PMID- 26425330
TI - Analyzing Short Message Services Application Effect on Diabetic Patients' Self
caring.
AB - BACKGROUND: Diabetes is the most prevalent metabolic disease with a growing
spread rate in word wide. Short message service (SMS) is of the most common
public communication networks, which have brought about a broad spectrum of
applications like social, cultural and service products in the late decade. The
objective of this research is, the investigate of using SMS on diabetes patients
self-caring. METHODS: In an interventional study, 228 diabetes patients have been
selected from a community charity. With using of random sampling method, they
were divided into two groups of 114 subjects as the control and case. The case
group was sent messages reminding them about sports, caring foot, taking insulin
and oral tablet for 4 weeks via mobile phone. After 4 weeks, a posttest
questionnaire was completed. The data analysis was performed using a descriptive
statistic, Chi-square, independent t-test, and paired t-test. RESULTS: There are
not significant differences between case and control groups before intervention
by studied dependent variables (P > 0.05). Performance score mean of taking care
of foot, sport and taking oral tablet and insulin in case group before
intervention were 29.90, 10, 11.16 and 3.75 respectively and after intervention
were 20.11, 41.36, 13.09 and 4.90, respectively. Furthermore, the performance
scores mean difference after intervention, taking care of foot (P < 0.001), sport
(P < 0.001), taking oral tablet (P = 0.020) was meaningful in case and control
groups. CONCLUSIONS: Regarding the study results on using cell phone, to utilize
virtual training methods is recommended as an appropriate procedure for different
health care, self-caring and follow-up training plans for various groups in
society, especially diabetic and chronic patients.
PMID- 26425331
TI - Spatial Analysis of Neonatal Congenital Hypothyroidism and Nitrate as an
Environmental Pollutant in Isfahan Province During 2010-2013.
AB - BACKGROUND: Thyroid absorption of iodine could be encumbered by nitrate drinking
water when it is transported to the fetal thyroid gland. Therefore, nitrate
potentially causes congenital hypothyroidism (CH) due to thyroid dysfunction. In
this study, we have not only aimed at spatial determination of CH distribution
and nitrate concentration (NC) existing in drinking water, but also we intended
to evaluate the probable impact of nitrate on CH incidence. METHODS: Annual
average of nitrate in drinking-water as well as number of CH infants diagnosed
through the screening program were applied to determine the incidence ratio of
the disease for each town (from 2010 to 2013). Afterward, Arc GIS 9.3 was used to
draw choropleth maps with quantile classification. Data were entered into SPSS
16.0 and Excel 2010 software. Finally, linear regression was applied for data
analysis. RESULTS: The incidence rate of CH (considering transient and permanent
cases) was about one in every 413 births. Khansar, Golpaygan, Naein, and Ardestan
had the highest incidence rate of CH respectively. On the other hand, Tiran,
Dehaghan, Khansar, and Fereydan had the highest level of nitrate drinking water.
There was a strong relationship between the NC and incidence of CH in Khansar;
however, this relationship was not significant (P = 0.392) in Isfahan province.
CONCLUSIONS: Since there was not a significant relationship between NC in
drinking-water and incidence of CH through linear regression analysis, more
studies should be implemented to confirm or refute our observations.
PMID- 26425332
TI - Methodology and Early Findings of the Assessment of Determinants of Weight
Disorders among Iranian Children and Adolescents: The Childhood and Adolescence
Surveillance and PreventIon of Adult Noncommunicable Disease-IV Study.
AB - BACKGROUND: This paper presents the methodology and primary findings of a
national project on determinants of weight disorders among Iranian children and
adolescents at national and sub-national levels. METHODS: This nationwide study
was conducted in 2011-2012 in Iran as part of the fourth phase of a national
surveillance program entitled Childhood and Adolescence Surveillance and
PreventIon of Adult Noncommunicable disease-IV study. It had two phases of
qualitative and quantitative study. This multicentric study was conducted among
25,000 students aged 6-18 years, living in urban and rural areas of 30 provinces
of Iran. Students were selected by multistage cluster sampling method. Data
regarding weight disorders including sociodemographic variables, perinatal
factors, lifestyle factors, family and student dietary habits, quality of life,
and family history of chronic diseases as well as body image were gathered via
validated questionnaires. RESULTS: Overall, 23043 students completed the survey
(participation rate: 92.17%). The mean age of participants was 12.55 +/- 3.31
years; 50.8% were boys, and 73.4% were from urban areas. Underweight was found in
10.4% of boys and 9.2% of girls, the corresponding figure for overweight and
obesity was 21% and 18.3%. Abdominal obesity was found in 17.6% of students.
Among parents, obesity was more frequent than other weight disorders, with higher
prevalence in parents of girls than boys (24.5% vs. 21.5%, respectively, P <
0.001). Overweight and obesity were more prevalent in urban than in rural parents
(66.7% vs. 59.7%, respectively, P < 0.001). CONCLUSIONS: This survey serves as
confirmatory evidence on the prevalence of dual burden of weight disorders in
Iran. Its findings on determinants of weight disorders would help policymakers to
implement relevant programs at national and sub-national levels.
PMID- 26425333
TI - Validation of Perceptual Strain Index to Evaluate the Thermal Strain in
Experimental Hot Conditions.
AB - BACKGROUND: The incidence of heat stress is one of the most common problems in
workplaces and industries. Many heat stress indices have been developed, and
these indices have some disadvantages. The purpose of this study is to validate
the perceptual strain index (PeSI) in experimental hot conditions. METHODS: This
study is of cross-sectional carried out on 15 men at five different thermal
conditions (35 degrees C, 30 degrees C, 27 degrees C, 24 degrees C, and 21
degrees C) in a climate chamber and on a treadmill at three levels of light (2.4
kph), medium (4.8 kph) and heavy activity (6.3 kph). Heart rate and oral
temperature were respectively measured to calculate the physiological strain
index. Also, thermal sensation and rate perceive exertion were respectively
measured to calculate the PeSI. Finally, the correlation between the indices was
analyzed using Pearson correlation test and regression analysis. RESULTS: Pearson
correlation test showed a high correlation (r = 0.94) between the PeSI and
physiological strain index (P = 0/001). It was also observed a high correlation
between the PeSI and the oral temperature (r = 0.78, P = 0/001) and the heart
rate (r = 0.90, P = 0/001). In addition, there was found a moderate correlation
(r = 0.71) between the PeSI and the wet bulb glob temperature (P = 0/001).
However, there was no correlation between the PeSI and the body mass index (r =
0.0009, P = 0.79). CONCLUSIONS: The research findings showed when there is no
access to other forms of methods to evaluate the heat stress, it can be used the
PeSI in evaluating the strain because of its favorable correlation with the
thermal strain.
PMID- 26425334
TI - Psycho-social Needs Impact on Hookah Smoking Initiation among Women: A
Qualitative Study from Iran.
AB - BACKGROUND: In Iranian women, the use of hookah is the most common method of
tobacco smoking. This study aimed to find the role of psycho-social needs and
gaps as a possible risk factor for hookah smoking initiation in women. METHODS:
This qualitative study was conducted during 2012-2013 in Tehran, Iran. Thirty-six
women participated in the study. They were current or former users of hookah.
Data were collected through in-depth individual interviews and was analyzed
through content analysis. RESULTS: Four main categories were identified from the
data. This study focused on the category: Psycho-social needs and gaps. This
category has five sub-categories which explain why women begin to smoke hookah
including curiosity; desire for non-feminine, forbidden, and negative activities;
need for amusement and recreation; for others: To show off; attract attention;
satisfy and join others and protection. CONCLUSIONS: From this study, a variety
of factors which contribute to the initiation of hookah smoking among women have
been identified. Keeping young girls and women away from seemingly happy
gatherings of hookah smokers; Providing appropriate recreational facilities for
young women and training families on how to help their children in the event of a
crisis-like intention to take up smoking behavior, can be some effective ways for
reducing hookah smoking initiation among women.
PMID- 26425335
TI - Demographic and other characteristics of nodal non-Hodgkin's lymphoma managed in
academic versus non-academic centers.
AB - BACKGROUND: Cancer therapy and outcomes are known to be affected by various
demographic features and hospital types. We aimed to identify the characteristics
of non-Hodgkin's lymphoma (NHL) patients associated with receipt of care at
academic centers. METHOD: This is a retrospective study of all patients diagnosed
with nodal NHL between 2000 and 2011 in the National Cancer Database (NCDB), who
received the diagnosis, and all or part of their initial therapy in the reporting
hospital (n = 243,436). Characteristics of patients receiving care in academic
versus nonacademic centers were compared using the Chi-square test. RESULTS:
Approximately 27% received care in academic centers. Patients receiving care in
nonacademic centers, compared with academic centers, were more likely to be ?60
years (69% versus 58%, p < .0001), White (89% versus 80%, p < .0001) and have
lower educational attainment (>12% without high school diploma: 72% versus 69%, p
< .0001) and economic status (household income <$49,000: 66% versus 61%, p <
0.0001). Patients receiving care in nonacademic centers were less likely to
travel ?25 miles (21% versus 26%, p < 0.0001). White patients, compared with non
Whites, were more likely to be ?60 years (70% versus <50%, p < 0.0001), which
probably explains less care in academic centers. CONCLUSIONS: Patients ?60 years
and those with poorer educational attainment and economic status were less likely
to receive care in academic centers. Care in academic centers required a longer
commute. Elderly patients frequently have inferior outcomes and may benefit from
clinical trials with novel agents and expertise at academic centers.
PMID- 26425336
TI - CD19-redirected chimeric antigen receptor-modified T cells: a promising
immunotherapy for children and adults with B-cell acute lymphoblastic leukemia
(ALL).
AB - Relapsed and chemotherapy-refractory B-cell acute lymphoblastic leukemia (B-ALL)
remain significant causes of cancer-associated morbidity and mortality for
children and adults. Development of new molecularly targeted treatment strategies
for patients with high-risk B-ALL is thus a major preclinical and clinical
priority. Adoptive cellular therapy with patient-derived human T cells
genetically engineered to express CD19 redirected chimeric antigen receptors
(CD19 CAR T cells) is one immunotherapeutic modality that has recently
demonstrated remarkable efficacy in re-inducing remission in patients with
multiply relapsed B-ALL. Investigative teams at several major cancer centers are
currently conducting phase I clinical trials in children and/or adults with
relapsed/refractory B-ALL to assess the safety and to identify the maximally
tolerated dose of each group's CD19 CAR T-cell product. All groups have reported
major clinical toxicities associated with CD19 CAR T-cell treatment, including
cytokine release syndrome (CRS) and macrophage activation syndrome, neurologic
dysfunction and aplasia of normal B lymphocytes, while CD19 CAR T cells persist
in vivo. Toxicities have generally been transient or manageable with supportive
care measures. Some patients with life-threatening CD19 CAR T-cell induced
sequelae have received anti-cytokine receptor antibody treatment to diminish CRS
symptoms and/or corticosteroids to terminate CAR T-cell proliferation.
Remarkably, 67-90% of children and adults with B-ALL treated with CD19 CAR T
cells in these trials have achieved morphologic leukemia remission with many
patients also in molecular remission. The duration of CD19 CAR T cell persistence
in vivo has varied appreciably among treated patients and likely reflects
differences in the CD19 CAR constructs utilized at each institution. CD19
positive and CD19-negative B-ALL relapses after CD19 CAR T-cell treatment have
occurred in some patients. Phase II trials to assess the efficacy of CD19 CAR T
cell immunotherapy in larger cohorts of patients with relapsed/refractory B-ALL
are ongoing or planned.
PMID- 26425338
TI - The clinical potential of inotuzumab ozogamicin in relapsed and refractory acute
lymphocytic leukemia.
AB - Antibody-drug conjugates (ADCs) are likely to make a significant contribution in
the treatment of acute lymphoblastic leukemia (ALL) by combining the cytotoxicity
of chemotherapy with the specificity of monoclonal antibodies. CD22, an endocytic
receptor expressed by the majority of B cells, is an excellent target for ADCs.
Inotuzumab ozogamicin (INO) is an ADC that consists of a cytotoxic moiety
(derivative of calicheamicin) attached to a humanized monoclonal anti-CD22
antibody. As a single agent, INO, was shown to be effective with an objective
response rate of 50% in the treatment of relapsed and refractory CD22 positive
ALL patients. Clinical trials investigating the combination of INO with the
conventional chemotherapies are ongoing. This review summarizes the clinical
potential of INO in treatment of relapsed and refractory ALL, based on currently
available data in the literature.
PMID- 26425337
TI - Ibrutinib in mantle cell lymphoma patients: glass half full? Evidence and
opinion.
AB - Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin's lymphoma typically
marked by an aggressive clinical course and a predilection for relapse. The B
cell receptor (BCR) signaling survival pathway is chronically activated in MCL,
contributing to its pathogenesis. Ibrutinib is an inhibitor of Bruton's tyrosine
kinase, a vital component of this pathway. This article details the current
clinical experience with ibrutinib in the treatment of patients with MCL,
including completed and published clinical trials and reviews potential adverse
events (AEs) and pitfalls associated with ibrutinib therapy. Although most AEs
experienced by patients treated with ibrutinib are mild, some can be severe and
treatment limiting and may be attributed to off-target effects. Ibrutinib is a
very promising agent for patients with MCL with notable response rates. However,
when used as a single agent, around one third of patients relapse in the first 2
years of treatment. Recently reported combination therapies have shown
significant activity. Emerging data evaluating potential mechanisms of drug
resistance and the poor clinical outcomes after treatment failure are also
discussed. Further understanding of resistance and its implications not only in
relapsed disease but in the frontline setting are needed. Investigation of
strategies to overcome resistance remains an area of high unmet clinical need.
Evaluation of the impact of shorter treatment duration, effects on minimal
residual disease, and incorporation of novel combinations are also warranted.
PMID- 26425340
TI - Kvik: three-tier data exploration tools for flexible analysis of genomic data in
epidemiological studies.
AB - Kvik is an open-source framework that we developed for explorative analysis of
functional genomics data from large epidemiological studies. Creating such
studies requires a significant amount of time and resources. It is therefore
usual to reuse the data from one study for several research projects. Often each
project requires implementing new analysis code, integration with specific
knowledge bases, and specific visualizations. Although existing data exploration
tools are available for single study data exploration, no tool provides all the
required functionality for multistudy data exploration. We have therefore used
the Kvik framework to develop Kvik Pathways, an application for exploring gene
expression data in the context of biological pathways. We have used Kvik Pathways
to explore data from both a cross-sectional study design and a case-control study
within the Norwegian Women and Cancer (NOWAC) cohort. Kvik Pathways follows the
three-tier architecture in web applications using a powerful back-end for
statistical analyses and retrieval of metadata.In this note, we describe how we
used the Kvik framework to develop the Kvik Pathways application. Kvik Pathways
was used by our team of epidemiologists toexplore gene expression data from
healthy women with high and low plasma ratios of essential fatty acids.
PMID- 26425339
TI - The role of IL-33 and mast cells in allergy and inflammation.
AB - Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) cytokine family.
It is preferentially and constitutively expressed in different structural cells
such as epithelial cells, endothelial cells, and smooth muscle cells. During
necrosis of these cells (after tissue injury or cell damage), the IL-33 that is
released may be recognized by different types of immune cells, such as
eosinophils, basophils and, especially, mast cells. IL-33 needs the specific
receptor ST2 (membrane-bound receptor) and Interleukin-1 receptor accessory
protein heterodimer for its binding, which instigates the production of different
types of cytokines and chemokines that have crucial roles in the exacerbation of
allergic diseases and inflammation. IL-33 and mast cells have been influentially
associated to the pathophysiology of allergic diseases and inflammation. IL-33 is
a crucial regulator of mast cell functions and might be an attractive therapeutic
target for the treatment of allergic and inflammatory diseases. In this review,
we summarize the current knowledge regarding the roles of IL-33 and mast cells in
the pathogenesis of allergies and inflammation.
PMID- 26425341
TI - Water immersion for post incident cooling of firefighters; a review of practical
fire ground cooling modalities.
AB - Rapidly cooling firefighters post emergency response is likely to increase the
operational effectiveness of fire services during prolonged incidents. A variety
of techniques have therefore been examined to return firefighters core body
temperature to safe levels prior to fire scene re-entry or redeployment. The
recommendation of forearm immersion (HFI) in cold water by the National Fire and
Protection Association preceded implementation of this active cooling modality by
a number of fire services in North America, South East Asia and Australia. The
vascularity of the hands and forearms may expedite body heat removal, however,
immersion of the torso, pelvis and/or lower body, otherwise known as multi
segment immersion (MSI), exposes a greater proportion of the body surface to
water than HFI, potentially increasing the rates of cooling conferred. Therefore,
this review sought to establish the efficacy of HFI and MSI to rapidly reduce
firefighters core body temperature to safe working levels during rest periods. A
total of 38 studies with 55 treatments (43 MSI, 12 HFI) were reviewed. The core
body temperature cooling rates conferred by MSI were generally classified as
ideal (n = 23) with a range of ~0.01 to 0.35 degrees C min(-1). In contrast, all
HFI treatments resulted in unacceptably slow core body temperature cooling rates
(~0.01 to 0.05 degrees C min(-1)). Based upon the extensive field of research
supporting immersion of large body surface areas and comparable logistics of
establishing HFI or MSI, it is recommended that fire and rescue management
reassess their approach to fireground rehabilitation of responders. Specifically,
we question the use of HFI to rapidly lower firefighter core body temperature
during rest periods. By utilising MSI to restore firefighter Tc to safe working
levels, fire and rescue services would adopt an evidence based approach to
maintaining operational capability during arduous, sustained responses. While the
optimal MSI protocol will be determined by the specifics of an individual
response, maximising the body surface area immersed in circulated water of up to
26 degrees C for 15 min is likely to return firefighter Tc to safe working
levels during rest periods. Utilising cooler water temperatures will expedite Tc
cooling and minimise immersion duration.
PMID- 26425344
TI - UEG E-learning: The future has arrived.
PMID- 26425342
TI - Effects of different colloid infusions on ROTEM and Multiplate during elective
brain tumour neurosurgery.
AB - BACKGROUND: The European Medicines Agency does not recommend the use of
hydroxyethyl starch-based volume replacement solutions in critically ill patients
due to an increased risk of renal failure. However, this recommendation is
questionable for its perioperative use. Several recent randomised controlled
studies do not indicate a risk for renal failure-not even after high-risk
surgery. Human albumin is used in our neurointensive care unit as a part of the
"Lund concept" of brain injury resuscitation, and albumin has been introduced in
elective neurosurgery instead of starch. The aim of our prospective unblinded
observational cohort study was to compare the degree of dilutive coagulopathy
after albumin and starch intra-operative fluid therapy. METHODS: Thirty-nine
patients undergoing elective brain tumour surgery with craniotomy received either
130/0.42 hydroxyethyl starch or 5 % albumin infusions. The first 18 patients
received starch, whereas the rest received albumin. Rotational thromboelastometry
with ROTEM and platelet aggregometry with Multiplate were performed before
surgery, after the first and second consecutive colloid infusions (250/500 ml
albumin or 500/1000 ml starch) and at the end of surgery. RESULTS: Both intra-
and inter-group comparisons showed more deranged ROTEM parameters after the
higher doses of starch. Multiplate detected changes only in the albumin group
after 500-ml infusion. Blood los did not differ between groups, nor did
haemoglobin preoperatively or at end of surgery. Lower volumes of albumin were
required to maintain stable intra-operative haemodynamic parameters; 250/500 ml
albumin corresponded to 500/1000 ml starch. CONCLUSIONS: Hydroxyethyl starch
affected coagulation at lower volumes, with a more prominent effect on clot
structure at the end of surgery, corroborating previous research. Only albumin
decreased platelet aggregation, and 5 % albumin had a more potential volume
effect than 130/0.42 hydroxyethyl starch.
PMID- 26425345
TI - What it means to receive the UEG Rising Star Award.
PMID- 26425346
TI - Young Talent Group introduces young guest editors for UEG Journal.
PMID- 26425343
TI - New developments and future opportunities in biomarkers for amyotrophic lateral
sclerosis.
AB - Modern technology has improved the ability to probe effectively the underlying
biology of ALS by examination of genomic, proteomic and physiological changes in
patients with ALS, as well as to monitor functional and structural changes during
the course of disease. While effective treatments for ALS are lacking, the
discovery of sensitive biomarkers to disease activity offers clinicians tools for
rapid diagnosis and insights into the pathophysiology of ALS. The ultimate aim is
to lessen reliance on clinical measures and survival as trial endpoints and
broaden the therapeutic options for patients with this disease.
PMID- 26425347
TI - Effect of therapeutic plasma exchange on plasma levels and total removal of
adipokines and inflammatory markers.
AB - BACKGROUND: Aside from well-established inflammatory mediators adipokines have
recently been found to play an important role in a variety of immunologic
diseases. Therapeutic plasma exchange (TPE) is an established treatment modality
for the acute removal of pathophysiological relevant disease mediators. The aim
of this study was to determine adipokine removal during TPE therapy. METHODS: 21
Caucasian patients (10 females, 11 males) with an indication for TPE using
albumin as exchange fluid received two consecutive TPE sessions. Blood samples
for measurement of resistin, leptin, sICAM-1, sCD40L, MCP-1, and sTNF-R were
drawn before and at the end of each TPE session. Samples from the total removed
plasma were collected at the end of every treatment. RESULTS: We found a
significant reduction in pre- vs. post-TPE plasma concentrations for sICAM-1 (517
+/- 246 vs. 260 +/- 159 ng/ml, p < 0.0001), sTNF-R (8.1 +/- 6.4 vs. 5.7 +/- 3.9
ng/ml, p < 0.05), and resistin plasma levels (14.3 +/- 6.9 vs. 9.5 +/- 4.7 ng/ml,
p < 0.001). Solely sICAM-1 reduction persisted for 25 +/- 5 h between the first
and second TPE treatment, while the other investigated mediators increased to
baseline levels. Substantial amounts of all measured mediators could be recovered
from the removed plasma. CONCLUSIONS: TPE provides a persistent reduction in
sICAM-1 levels and temporarily affects several adipokine and cytokine plasma
levels. Our findings are of importance not only for the interpretation of blood
levels of cytokines in patients undergoing TPE but provide solid evidence that
TPE markedly decreases sICAM-1.
PMID- 26425348
TI - Vitreomacular Interface: From Anterior to Tangential Traction.
PMID- 26425349
TI - The Vitreomacular Interface in Diabetic Retinopathy.
AB - Diabetic retinopathy (DR) is a leading health concern and a major cause of
blindness. DR can be complicated by scar tissue formation, macular edema, and
tractional retinal detachment. Optical coherence tomography has found that
patients with DR often have diffuse retinal thickening, cystoid macular edema,
posterior hyaloid traction, and tractional retinal detachment. Newer imaging
techniques can even detect fine tangential folds and serous macular detachment.
The interplay of the vitreous and the retina in the progression of DR involves
multiple chemokine and other regulatory factors including VEGF. Understanding the
cells infiltrating pathologic membranes at the vitreomacular interface has opened
up the possibility of new targets for pharmacotherapy. Vitrectomies for DR remain
a vital tool to help relieve tension on the macula by removing membranes,
improving edema absorption, and eliminating the scaffold for new membrane
formation. Newer treatments such as triamcinolone acetonide and VEGF inhibitors
have become essential as a rapid way to control DR at the vitreomacular
interface, improve macular edema, and reduce retinal neovascularization. These
treatments alone, and in conjunction with PRP, help to prevent worsening of the
VMI in patients with DR.
PMID- 26425350
TI - Correlative Microscopy of Lamellar Hole-Associated Epiretinal Proliferation.
AB - Purpose. To describe morphology of lamellar hole-associated epiretinal
proliferation (LHEP) removed from eyes with lamellar macular holes (LMH).
Methods. Based on optical coherence tomography data, 10 specimens of LHEP were
removed from 10 eyes with LMH during standard vitrectomy. Specimens were prepared
for correlative light and electron microscopy (CLEM) using an immunonanogold
particle of 1.4 nm diameter that was combined with a fluorescein moiety, both
having been attached to a single antibody fragment. As primary antibodies, we
used antiglial fibrillary acidic protein (GFAP), anti-CD45, anti-CD64, anti-alpha
smooth muscle actin (alpha-SMA), and anticollagen type I and type II. Results. In
LHEP, GFAP-positive cells possess ultrastructural characteristics of fibroblasts
and hyalocytes. They represent the major cell types and were densely packed in
cell agglomerations on vitreous collagen strands. Epiretinal cells of LHEP rarely
demonstrated contractive properties as alpha-SMA-positive myofibroblasts were an
infrequent finding. Conclusion. CLEM indicates that epiretinal cells in LHEP
might originate from the vitreous and that remodelling processes of vitreous
collagen may play an important role in pathogenesis of eyes with LMH.
PMID- 26425353
TI - Is the Memory Effect of the Blind Spot Involved in Negative Dysphotopsia after
Cataract Surgery?
AB - We present novel clinical observations on negative dysphotopsia (ND) in eyes that
have undergone cataract surgery. In the past, shadow effects were alleged to be
located in the far peripheral temporal visual field 50 degrees to 100 degrees
away from the optical axis. In a small series of eight patients we found evidence
of photic effects, described by the patients as shadows in the periphery that
were objectively located much more centrally. In all cases, we could find an
association of these phenomena with the blind spot. We hypothesize that the
memory effect of the blind spot which is dislocated and changed in magnification
due to replacement of the crystalline lens could be one determinant for
pseudophakic ND. The scotoma of the optic nerve head and the main arteries and
veins of the phakic eye are displaced in the pseudophakic eye depending on the
specific characteristics and position of the intraocular lens within the eye.
PMID- 26425352
TI - Current Trends about Inner Limiting Membrane Peeling in Surgery for Epiretinal
Membranes.
AB - The inner limiting membrane (ILM) is the basement membrane of the Muller cells
and can act as a scaffold for cellular proliferation in the pathophysiology of
disorders affecting the vitreomacular interface. The atraumatic removal of the
macular ILM has been proposed for treating various forms of tractional
maculopathy in particular for macular pucker. In the last decade, the removal of
ILM has become a routine practice in the surgery of the epiretinal membranes
(ERMs), with good anatomical results. However many recent studies showed that ILM
peeling is a procedure that can cause immediate traumatic effects and progressive
modification on the underlying inner retinal layers. Moreover, it is unclear
whether ILM peeling is helpful to improve vision after surgery for ERM. In this
review, we describe the current understanding about ILM peeling and highlight the
beneficial and adverse effects associated with this surgical procedure.
PMID- 26425354
TI - Effects of Vitreomacular Adhesion on Age-Related Macular Degeneration.
AB - Herein, we review the association between vitreomacular adhesion (VMA) and
neovascular age-related macular degeneration (AMD). Meta-analyses have shown that
eyes with neovascular AMD are twice as likely to have VMA as normal eyes. VMA in
neovascular AMD may induce inflammation, macular traction, decrease in
oxygenation, sequestering of vascular endothelial growth factor (VEGF), and other
cytokines or may directly stimulate VEGF production. VMA may also interfere with
the treatment effects of anti-VEGF therapy, which is the standard treatment for
neovascular AMD, and releasing VMA can improve the treatment response to anti
VEGF treatment in neovascular AMD. We also reviewed currently available methods
of relieving VMA.
PMID- 26425355
TI - Retinal Damage Induced by Internal Limiting Membrane Removal.
AB - The internal limiting membrane (ILM), the basement membrane of the Muller cells,
serves as the interface between the vitreous body and the retinal nerve fiber
layer. It has a fundamental role in the development, structure, and function of
the retina, although it also is a pathologic component in the various
vitreoretinal disorders, most notably in macular holes. It was not until
understanding of the evolution of idiopathic macular holes and the advent of
idiopathic macular hole surgery that the idea of adjuvant ILM peeling in the
treatment of tractional maculopathies was explored. Today intentional ILM peeling
is a commonly applied surgical technique among vitreoretinal surgeons as it has
been found to increase the rate of successful macular hole closure and improve
surgical outcomes in other vitreoretinal diseases. Though ILM peeling has refined
surgery for tractional maculopathies, like all surgical procedures it is not
immune to perioperative risk. The essential role of the ILM to the integrity of
the retina and risk of trauma to retinal tissue spurs suspicion with regard to
its routine removal. Several authors have investigated the retinal damage induced
by ILM peeling and these complications have been manifested across many different
diagnostic studies.
PMID- 26425356
TI - Advances in atomic physics: Four decades of contribution of the Cairo University
Atomic Physics Group.
AB - In this review article, important developments in the field of atomic physics are
highlighted and linked to research works the author was involved in himself as a
leader of the Cairo University - Atomic Physics Group. Starting from the late
1960s - when the author first engaged in research - an overview is provided of
the milestones in the fascinating landscape of atomic physics.
PMID- 26425351
TI - Complications of Macular Peeling.
AB - Macular peeling refers to the surgical technique for the removal of preretinal
tissue or the internal limiting membrane (ILM) in the macula for several retinal
disorders, ranging from epiretinal membranes (primary or secondary to diabetic
retinopathy, retinal detachment...) to full-thickness macular holes, macular
edema, foveal retinoschisis, and others. The technique has evolved in the last
two decades, and the different instrumentations and adjuncts have progressively
advanced turning into a safer, easier, and more useful tool for the vitreoretinal
surgeon. Here, we describe the main milestones of macular peeling, drawing
attention to its associated complications.
PMID- 26425358
TI - New algorithms for solving third- and fifth-order two point boundary value
problems based on nonsymmetric generalized Jacobi Petrov-Galerkin method.
AB - Two families of certain nonsymmetric generalized Jacobi polynomials with negative
integer indexes are employed for solving third- and fifth-order two point
boundary value problems governed by homogeneous and nonhomogeneous boundary
conditions using a dual Petrov-Galerkin method. The idea behind our method is to
use trial functions satisfying the underlying boundary conditions of the
differential equations and the test functions satisfying the dual boundary
conditions. The resulting linear systems from the application of our method are
specially structured and they can be efficiently inverted. The use of generalized
Jacobi polynomials simplify the theoretical and numerical analysis of the method
and also leads to accurate and efficient numerical algorithms. The presented
numerical results indicate that the proposed numerical algorithms are reliable
and very efficient.
PMID- 26425357
TI - Synthesis, cloning and expression of a novel pre-miniproinsulin analogue gene in
Escherichia coli.
AB - In the present study, a novel pre-miniproinsulin analogue was designed to have a
short 9 residue sequence replacing the 35 residue C-chain, one lysine and one
arginine added to the C-terminus of the B-chain in combination with glycine and
arginine substitution at A21 and B29, respectively, and a 16-residue fusion
partner comprising the pentapeptide sequence (PSDKP) of the N-terminus of human
tumor necrosis factor-alpha (TNF-alpha), 6 histidine residues for Ni(2+) chelated
affinity purification and a pentapeptide ending with methionine for ease of
chemical cleavage fused at the N-terminus. Homology modeling of the designed
protein against miniproinsulin (protein databank file 1 efeA) as a template
showed that the distance between the alpha-carbons of the C-terminus of the B
chain and the N-terminus of the A-chain did not change; the root-mean-square
deviation of the backbone atoms between the structures of modeled miniproinsulin
and miniproinsulin template was 0.000 A. DNA sequencing of the synthesized gene
showed 100% identity with theoretical sequence. The gene was constructed taking
into account the codon preference of Escherichia coli (CAI value 0.99) in order
to increase the expression rate of the DNA in the host strain. The designed gene
was synthesized using DNA synthesis technology and then cloned into the
expression plasmid pET-24a(+) and propagated in E. coli strain JM109. Gene
expression was successful in two E. coli strains: namely JM109(DE3) and
BL21(DE3)pLysS. SDS-PAGE analysis was carried out to check protein size and to
check and optimize expression. Rapid screening and purification of the resulting
protein was carried out by Ni-NTA technology. The identity of the expressed
protein was verified by immunological detection method of western blot using
polyclonal rabbit antibody against insulin.
PMID- 26425360
TI - Statistical analysis of the effective factors on the 28 days compressive strength
and setting time of the concrete.
AB - In this study, the effects of various factors (weight fraction of the SiO2,
Al2O3, Fe2O3, Na2O, K2O, CaO, MgO, Cl, SO3, and the Blaine of the cement
particles) on the concrete compressive strength and also initial setting time
have been investigated. Compressive strength and setting time tests have been
carried out based on DIN standards in this study. Interactions of these factors
have been obtained by the use of analysis of variance and regression equations of
these factors have been obtained to predict the concrete compressive strength and
initial setting time. Also, simple and applicable formulas with less than 6%
absolute mean error have been developed using the genetic algorithm to predict
these parameters. Finally, the effect of each factor has been investigated when
other factors are in their low or high level.
PMID- 26425359
TI - An intelligent approach for variable size segmentation of non-stationary signals.
AB - In numerous signal processing applications, non-stationary signals should be
segmented to piece-wise stationary epochs before being further analyzed. In this
article, an enhanced segmentation method based on fractal dimension (FD) and
evolutionary algorithms (EAs) for non-stationary signals, such as
electroencephalogram (EEG), magnetoencephalogram (MEG) and electromyogram (EMG),
is proposed. In the proposed approach, discrete wavelet transform (DWT)
decomposes the signal into orthonormal time series with different frequency
bands. Then, the FD of the decomposed signal is calculated within two sliding
windows. The accuracy of the segmentation method depends on these parameters of
FD. In this study, four EAs are used to increase the accuracy of segmentation
method and choose acceptable parameters of the FD. These include particle swarm
optimization (PSO), new PSO (NPSO), PSO with mutation, and bee colony
optimization (BCO). The suggested methods are compared with other most popular
approaches (improved nonlinear energy operator (INLEO), wavelet generalized
likelihood ratio (WGLR), and Varri's method) using synthetic signals, real EEG
data, and the difference in the received photons of galactic objects. The results
demonstrate the absolute superiority of the suggested approach.
PMID- 26425361
TI - Bearing capacity of shell strip footing on reinforced sand.
AB - In this paper, the ultimate load capacities of shell foundations on unreinforced
and reinforced sand were determined by laboratory model tests. A series of
loading tests were carried out on model shell footing with and without single
layer of reinforcement. The tests were done for shell foundation at different
shell embedment depth and subgrade density. The results were compared with those
for flat foundations without reinforcement. The model test results were verified
using finite element analysis using program PLAXIS. The experimental studies
indicated that, the ultimate load capacity of shell footing on reinforced
subgrade is higher than those on unreinforced cases and the load settlement
curves were significantly modified. The shell foundation over reinforced subgrade
can be considered a good method to increase the effective depth of the foundation
and decrease the resulting settlement. Also the rupture surface of shell
reinforced system was significantly deeper than both normal footing and shell
footing without reinforcement. The numerical analysis helps in understanding the
deformation behavior of the studied systems and identifies the failure surface of
reinforced shell footing.
PMID- 26425362
TI - Principal component analysis of cardiovascular risk traits in three generations
cohort among Indian Punjabi population.
AB - The current study focused to determine significant cardiovascular risk factors
through principal component factor analysis (PCFA) among three generations on
1827 individuals in three generations including 911 males (378 from offspring,
439 from parental and 94 from grand-parental generations) and 916 females (261
from offspring, 515 from parental and 140 from grandparental generations). The
study performed PCFA with orthogonal rotation to reduce 12 inter-correlated
variables into groups of independent factors. The factors have been identified as
2 for male grandparents, 3 for male offspring, female parents and female
grandparents each, 4 for male parents and 5 for female offspring. This data
reduction method identified these factors that explained 72%, 84%, 79%, 69%, 70%
and 73% for male and female offspring, male and female parents and male and
female grandparents respectively, of the variations in original quantitative
traits. The factor 1 accounting for the largest portion of variations was
strongly loaded with factors related to obesity (body mass index (BMI), waist
circumference (WC), waist to hip ratio (WHR), and thickness of skinfolds) among
all generations with both sexes, which has been known to be an independent
predictor for cardiovascular morbidity and mortality. The second largest
components, factor 2 and factor 3 for almost all generations reflected traits of
blood pressure phenotypes loaded, however, in male offspring generation it was
observed that factor 2 was loaded with blood pressure phenotypes as well as
obesity. This study not only confirmed but also extended prior work by developing
a cumulative risk scale from factor scores. Till today, such a cumulative and
extensive scale has not been used in any Indian studies with individuals of three
generations. These findings and study highlight the importance of global approach
for assessing the risk and need for studies that elucidate how these different
cardiovascular risk factors interact with each other over the time to create
clinical disease. The findings also added depth to the negligible amount of
literature of factor analysis of cardiovascular risk in any Indian ethnic
population.
PMID- 26425363
TI - Expression, genetic localization and phylogenic analysis of NAPlr in piscine
Streptococcus dysgalactiae subspecies dysgalactiae isolates and their patterns of
adherence.
AB - Streptococcus dysgalactiae, the long recognized mammalian pathogen, has currently
received a major concern regarding fish bacterial infection. Adhesion to host
epithelial cells and the presence of wall-associated plasminogen binding proteins
are prerequisites to Streptococcus infection. This is the first study of the
occurrence of nephritis-associated plasminogen-binding receptor (NAPlr) and alpha
enolase genes in piscine S. dysgalactiae subspecies dysgalactiae (SDSD) isolates.
Further characterization of surface localized NAPlr of fish SDSD revealed a
similar immune-reactive band of 43 KDa as that from porcine S. dysgalactiae
subsp. equisimilis (SDSE). The phylogenetic analysis revealed that NAPlr of fish
SDSD is more associated with those of mammalian SDSE and Streptococcus pyogenes
rather than of other streptococci. Our findings warrant public attention to the
possible implication of these virulence genes in dissemination of SDSD to
different tissues of infected hosts and to get advantage to new niches. The SDSD
adherence patterns were also studied to better understand their pathogenicity.
The patterns of adherence of SDSD on two different cell lines showed a different
pattern of adherence. Such difference gives an insight about the variance in host
susceptibility to infection.
PMID- 26425364
TI - Effect of laser acupuncture combined with a diet-exercise intervention on
metabolic syndrome in post-menopausal women.
AB - This study aimed to evaluate the effect of laser acupuncture combined with a diet
exercise intervention on features of the metabolic syndrome (MetS). Twenty-eight
obese post-menopausal women were randomly distributed to the control and laser
acupuncture group. The control group received the diet-exercise intervention and
the study group received the same intervention and sessions of laser acupuncture,
3 times/week for 12 weeks. Anthropometric measurement, fasting blood glucose and
insulin levels, homeostatic model assessment-insulin resistance (HOMA-IR), and
lipid profile were assessed before and after the treatment course. Both groups
showed a significant decrease in the anthropometric and metabolic parameters.
However, laser acupuncture group showed a greater decrease in the waist (P =
0.001) and hip (P = 0.001) circumferences, cholesterol (P = 0.04), and insulin
levels (P = 0.043) than the control group. These results suggest that laser
acupuncture is a valuable approach that could be added to the diet-exercise
intervention to correct features of the MetS.
PMID- 26425365
TI - The MANGUA Project: A Population-Based HIV Cohort in Guatemala.
AB - Introduction. The MANGUA cohort is an ongoing multicenter, observational study of
people living with HIV/AIDS in Guatemala. The cohort is based on the MANGUA
application which is an electronic database to capture essential data from the
medical records of HIV patients in care. Methods. The cohort enrolls HIV-positive
adults >=16 years of age. A predefined set of sociodemographic, behavioral,
clinical, and laboratory data are registered at entry to the cohort study.
Results. As of October 1st, 2012, 21 697 patients had been included in the MANGUA
cohort (median age: 33 years, 40.3% female). At enrollment 74.1% had signs of
advanced HIV infection and only 56.3% had baseline CD4 cell counts. In the first
12 months after starting antiretroviral treatment 26.9% (n = 3938) of the
patients were lost to the program. Conclusions. The implementation of a cohort of
HIV-positive patients in care in Guatemala is feasible and has provided national
HIV indicators to monitor and evaluate the HIV epidemic. The identified
percentages of late presenters and high rates of LTFU will help the Ministry to
target their current efforts in improving access to diagnosis and care.
PMID- 26425366
TI - Open and Closed Endotracheal Suctioning and Arterial Blood Gas Values: A Single
Blind Crossover Randomized Clinical Trial.
AB - Aim. This study was aimed at comparing the effects of the open and closed
suctioning techniques on the arterial blood gas values in patients undergoing
open-heart surgery. Methods. In a clinical trial, we recruited 42 patients after
open-heart surgery in an educational hospital. Each patient randomly underwent
both open and closed suctioning. ABGs, PaO2, SaO2, PaCO2, were analyzed before
and one, five, and fifteen minutes after each suctioning episode. Results. At
first the pressure of oxygen in arterial blood increased; however, this increase
in the open technique was greater than that of the closed system (P < 0.001). The
pressure of oxygen decreased five and fifteen minutes after both suctioning
techniques (P < 0.05). The trends of carbon dioxide variations after the open and
closed techniques were upward and downward, respectively. Moreover, the decrease
in the level of oxygen saturation five and fifteen minutes after the open
suctioning was greater than that of the closed suctioning technique (P < 0.05).
Conclusion. Arterial blood gas disturbances in the closed suctioning technique
were less than those of the open technique. Therefore, to eliminate the unwanted
effects of endotracheal suctioning on the arterial blood gases, the closed
suctioning technique is recommended.
PMID- 26425367
TI - Influence of Individual Surgeon Volume on Oncological Outcome of Colorectal
Cancer Surgery.
AB - BACKGROUND: Surgery performed by a high-volume surgeon improves short-term
outcomes. However, not much is known about long-term effects. Therefore we
performed the current study to evaluate the impact of high-volume colorectal
surgeons on survival. METHODS: We conducted a retrospective analysis of our
prospectively collected colorectal cancer database between 2004 and 2011.
Patients were divided into two groups: operated on by a high-volume surgeon (>25
cases/year) or by a low-volume surgeon (<25 cases/year). Perioperative data were
collected as well as follow-up, recurrence rates, and survival data. RESULTS: 774
patients underwent resection for colorectal malignancies. Thirteen low-volume
surgeons operated on 453 patients and 4 high-volume surgeons operated on 321
patients. Groups showed an equal distribution for preoperative characteristics,
except a higher ASA-classification in the low-volume group. A high-volume surgeon
proved to be an independent prognostic factor for disease-free survival in the
multivariate analysis (P = 0.04). Although overall survival did show a
significant difference in the univariate analysis (P < 0.001) it failed to reach
statistical significance in the multivariate analysis (P = 0.09). CONCLUSIONS: In
our study, a higher number of colorectal cases performed per surgeon were
associated with longer disease-free survival. Implementing high-volume surgery
results in improved long-term outcome following colorectal cancer.
PMID- 26425368
TI - Central Sensitization and Perceived Indoor Climate among Workers with Chronic
Upper-Limb Pain: Cross-Sectional Study.
AB - Monitoring of indoor climate is an essential part of occupational health and
safety. While questionnaires are commonly used for surveillance, not all workers
may perceive an identical indoor climate similarly. The aim of this study was to
evaluate perceived indoor climate among workers with chronic pain compared with
pain-free colleagues and to determine the influence of central sensitization on
this perception. Eighty-two male slaughterhouse workers, 49 with upper-limb
chronic pain and 33 pain-free controls, replied to a questionnaire with 13 items
of indoor climate complaints. Pressure pain threshold (PPT) was measured in
muscles of the arm, shoulder, and lower leg. Cross-sectional associations were
determined using general linear models controlled for age, smoking, and job
position. The number of indoor climate complaints was twice as high among workers
with chronic pain compared with pain-free controls (1.8 [95% CI: 1.3-2.3] versus
0.9 [0.4-1.5], resp.). PPT of the nonpainful leg muscle was negatively associated
with the number of complaints. Workers with chronic pain reported more indoor
climate complaints than pain-free controls despite similar actual indoor climate.
Previous studies that did not account for musculoskeletal pain in questionnaire
assessment of indoor climate may be biased. Central sensitization likely explains
the present findings.
PMID- 26425369
TI - Naegele Forceps Delivery and Association between Morbidity and the Number of
Forceps Traction Applications: A Retrospective Study.
AB - OBJECTIVE: To present the method of Naegele forceps delivery clinically practiced
by the lead author, its success rate, and morbidity and to evaluate the
relationship between morbidity and the number of forceps traction applications.
METHODS: Naegele forceps delivery was performed when the fetal head reached
station +2 cm, the forceps were applied in the maternal pelvic application, and
traction was slowly and gently performed. In the past two years, Naegele forceps
delivery was attempted by the lead author in 87 cases, which were retrospectively
reviewed. RESULTS: The numbers of traction applications were one in 64.7% of
cases, two in 24.7%, and three or more in 10.7%. The success rate was 100%. No
severe morbidity was observed in mothers or neonates. Neonatal facial injury
occurred most commonly in cases with fetal head malrotation, elevated numbers of
traction applications, and maternal complications. Umbilical artery acidemia most
commonly occurred in cases with nonreassuring fetal status. The significant crude
odds ratio for three or more traction applications was 20 in cases with
malrotation. CONCLUSION: Naegele forceps delivery has a high success rate, but
multiple traction applications will sometimes be required, particularly in cases
with malrotation. Malrotation and elevated numbers of traction applications may
lead to neonatal head damage.
PMID- 26425371
TI - Constrictive Pericarditis: A Challenging Diagnosis in Paediatrics.
AB - Constrictive pericarditis is an uncommon disease in children, usually difficult
to diagnose. We present the case of a 14-year-old boy with a previous history of
tuberculosis and right heart failure, in whom constrictive pericarditis was
diagnosed. The case highlights the need to integrate all information, including
clinical data, noninvasive cardiac imaging, and even invasive hemodynamic
evaluation when required, in order to establish the correct diagnosis and proceed
to surgical treatment.
PMID- 26425372
TI - Conventional Complete Denture in Patients with Ectodermal Dysplasia.
AB - Ectodermal dysplasia is described as heritable conditions that involve anomalies
of structures derived from the ectoderm, including hypodontia. In the cases of
edentulous young patients, who did not finish their craniofacial growth,
treatment with conventional complete denture is a suitable alternative. The aim
of this study was to report a case of mandibular edentulism treated with
conventional complete denture in a thirteen-year-old patient diagnosed with
hidrotic ectodermal dysplasia. Typical features, such as frontal bossing,
depressed nasal bridge, protuberant lips, scarce hair, and brittle nails, were
visualized during the extraoral examination. The intraoral inspection and
radiographic analysis revealed oligodontia, dental malformation, and prolonged
retention of deciduous teeth at maxilla and total edentulism at mandible. A
conventional complete denture was planned and constructed following the same
steps of technique as recommended in adults. Although this option is not a
definitive treatment, the patient and his parents were satisfied with his
improvement in chewing and speech, as well as with the aesthetic benefits.
PMID- 26425370
TI - Audiomotor Integration in Minimally Conscious State: Proof of Concept!
AB - Patients suffering from chronic disorders of consciousness (DOC) are
characterized by profound unawareness and an impairment of large-scale cortical
and subcortical connectivity. In this study, we applied an electrophysiological
approach aimed at identifying the residual audiomotor connectivity patterns that
are thought to be linked to awareness. We measured some markers of audiomotor
integration (AMI) in 20 patients affected by DOC, before and after the
application of a repetitive transcranial magnetic stimulation protocol (rTMS)
delivered over the left primary motor area (M1), paired to a transauricular
alternating current stimulation. Our protocol induced potentiating of the
electrophysiological markers of AMI and M1 excitability, paired to a clinical
improvement, in all of the patients with minimally conscious state (MCS) but in
none of those suffering from unresponsive wakefulness syndrome (UWS). Our
protocol could be a promising approach to potentiate the functional connectivity
within large-scale audiomotor networks, thus allowing clinicians to differentiate
patients affected by MCS from UWS, besides the clinical assessment.
PMID- 26425373
TI - Interdisciplinary Approach to a Tooth with Open Apex and Persistent Sinus.
AB - Traumatic injuries in childhood may disrupt root development leading to a tooth
with open apex. Apexification procedures in such cases aim at root end closure
after reasonable period of time. In some chronic cases, complete healing of the
periapical area does not occur resulting in development of a nonhealing sinus.
Failure of nonsurgical approach in such cases needs surgical intervention
permitting thorough periapical curettage. In the present case, apexification
procedure with MTA achieved root end closure but failed to heal the sinus for
which surgical treatment was completed with thorough periapical curettage and
application of platelet rich fibrin (PRF) and a combination of beta-tricalcium
phosphate and hydroxyapatite resulted in healing.
PMID- 26425374
TI - Reconstruction of a Large Anterior Ear Defect after Mohs Micrographic Surgery
with a Cartilage Graft and Postauricular Revolving Door Flap.
AB - A novel postauricular revolving door island flap and cartilage graft combination
was employed to correct a large defect on the anterior ear of an 84-year-old man
who underwent Mohs micrographic surgery for an antihelical squamous cell
carcinoma. The defect measured 4.6 * 2.4 cm and spanned the antihelix, scapha, a
small portion of the helix, and a large segment of underlying cartilage, with
loss of structural integrity and anterior folding of the ear. The repair involved
harvesting 1.5 cm(2) of exposed cartilage from the scaphoid fossa and then
sculpting and suturing it to the remnant of the antihelical cartilage in order to
recreate the antihelical crura. The skin of the posterior auricle was then
incised just below the helical rim and folded anteriorly to cover the cartilage
graft. The flap remained attached by a central subcutaneous pedicle, and an
island designed using the full-thickness defect as a stencil template was pulled
through the cartilage window anteriorly to resurface the anterior ear. This case
demonstrates the use of the revolving door flap for coverage of large central ear
defects with loss of cartilaginous support and illustrates how cartilage grafts
may be used in combination with the flap to improve ear contour after resection.
PMID- 26425375
TI - Lithium as an Alternative Option in Graves Thyrotoxicosis.
AB - A 67-year-old woman was admitted with signs and symptoms of Graves
thyrotoxicosis. Biochemistry results were as follows: TSH was undetectable; FT4
was >6.99 ng/dL (0.7-1.8); FT3 was 18 pg/mL (3-5); TSI was 658% (0-139). Thyroid
uptake and scan showed diffusely increased tracer uptake in the thyroid gland.
The patient was started on methimazole 40 mg BID, but her LFTs elevated
precipitously with features of fulminant hepatitis. Methimazole was determined to
be the cause and was stopped. After weighing pros and cons, lithium was initiated
to treat her persistent thyrotoxicosis. Lithium 300 mg was given daily with a
goal to maintain between 0.4 and 0.6. High dose Hydrocortisone and propranolol
were also administered concomitantly. Free thyroid hormone levels decreased and
the patient reached a biochemical and clinical euthyroid state in about 8 days.
Though definitive RAI was planned, the patient has been maintained on lithium for
more than a month to control her hyperthyroidism. Trial removal of lithium
results in reemergence of thyrotoxicosis within 24 hours. Patient was maintained
on low dose lithium treatment with lithium level just below therapeutic range
which was sufficient to maintain euthyroid state for more than a month. There
were no signs of lithium toxicity within this time period. Conclusion. Lithium
has a unique physiologic profile and can be used to treat thyrotoxicosis when
thionamides cannot be used while awaiting elective radioablation. Lithium levels
need to be monitored; however, levels even at subtherapeutic range may be
sufficient to treat thyrotoxicosis.
PMID- 26425376
TI - Fatal Epstein-Barr Virus Reactivation in an Acquired Aplastic Anemia Patient
Treated with Rabbit Antithymocyte Globulin and Cyclosporine A.
AB - Epstein-Barr virus (EBV) associated lymphoproliferative disorder (LPD) after
immunosuppressive therapy for aplastic anemia (AA) is extremely rare in a
nontransplant setting and has not been well described. This report describes a
severe AA patient in whom fatal EBV-LPD developed after being treated with rabbit
antithymocyte globulins (ATG) and cyclosporine A (CsA). An 81-year-old man was
diagnosed as having severe AA. He was started on CsA followed by administration
of ATG for five consecutive days. One month after the start of ATG, persistent
fever which was not responsive to antibiotics or antifungal agents developed and
atypical lymphocytes emerged in peripheral blood. Repeated blood cultures were
negative. An extremely high level of EBV virus in his peripheral blood plasma was
detected by means of a quantitative real-time PCR assay. Even after the cessation
of CsA, the fever persisted and the peripheral atypical lymphocytes proliferated
rapidly. The patient suffered from respiratory failure, liver dysfunction, and
metabolic acidosis. Rituximab was administered without success and he died.
PMID- 26425377
TI - Behcet's Disease with Intracardiac Thrombus Presenting with Fever of Unknown
Etiology.
AB - A young male was referred to us for evaluation of fever of unknown origin (FUO).
He had history of recurrent painful oral ulcers for one year and moderate to high
grade fever, pustulopapular rash, and recurrent genital ulcers for 6 months and
hemoptysis for 3 days. He was detected to have intracardiac thrombi and pulmonary
arterial thrombosis along with underlying Behcet's disease (BD). Patient
responded to high dose prednisolone (1 mg/Kg/day) along with monthly parenteral
cyclophosphamide therapy. This case highlights the fact that BD is an important
cause for pulmonary artery vasculitis with intracardiac thrombus formation, and
such patients can present with FUO.
PMID- 26425378
TI - Hyperchloremic Metabolic Acidosis due to Cholestyramine: A Case Report and
Literature Review.
AB - Cholestyramine is a bile acid sequestrant that has been used in the treatment of
hypercholesterolemia, pruritus due to elevated bile acid levels, and diarrhea due
to bile acid malabsorption. This medication can rarely cause hyperchloremic
nonanion gap metabolic acidosis, a complication featured in this report of an
adult male with concomitant acute kidney injury. This case emphasizes the caution
that must be taken in prescribing cholestyramine to patients who may also be
volume depleted, in renal failure, or taking spironolactone.
PMID- 26425379
TI - STA-MCA Bypass as a "Bridge" to Pituitary Surgery in a Patient with an Adenoma
Occluding the Internal Carotid Artery: Case Report and Review of the Literature.
AB - Occlusion of the intracranial internal carotid artery (ICA) by a pituitary
adenoma with resulting cerebral ischemia is a very rare but devastating
occurrence. The authors present a case in which a condition of symptomatic ICA
occlusion due to a giant pituitary adenoma was successfully treated using a
preliminary extraintracranial bypass as a "bridge" to the tumor removal. A 52
year-old patient presented with a minor stroke followed by pressure-dependent
transient ischemic attacks consistent with a condition of hypoperfusion. MR
imaging and a digital subtraction angiography revealed a pituitary adenoma
occluding the ICA on the right side. He underwent a superficial temporal artery
to middle cerebral artery (STA-MCA) bypass with the aim of revascularizing the
ischemic hemisphere and reducing the risk of perioperative stroke or stroke
evolution. The patient was subsequently operated on to remove the adenoma through
a transsphenoidal approach. The postoperative course was uneventful and the
patient has suffered no further ischemic events. When there are no emergency
indications to decompress the optical pathways but the patient is at risk of
impending stroke because of ICA occlusion, a two-step strategy consisting of a
bypass and subsequent removal of the pituitary adenoma may be a valuable option.
PMID- 26425380
TI - Ledderhose Disease: Clinical, Radiological (Ultrasound and MRI), and
Anatomopathological Findings.
AB - Plantar fibromatosis, or Ledderhose disease, is a rare hyperproliferative
disorder of the plantar aponeurosis. It may occur at any age, with the greatest
prevalence at middle age and beyond. This disorder is more common in men than
woman and it is sometimes associated with other forms of fibromatosis. Diagnosis
is based on clinical examination. Ultrasound (US) and magnetic resonance imaging
(MRI) can be useful to confirm the diagnosis. A 44-year-old man with Ledderhose
disease who underwent ultrasound and MR is described in this paper.
PMID- 26425381
TI - Bilateral Simultaneous Avulsion Fractures of the Proximal Tibia in a 14-Year-Old
Athlete with Vitamin-D Deficiency.
AB - Fractures involving the proximal tibial epiphysis are rare and form 0.5% of all
epiphyseal injuries. The specific anatomical and developmental features of the
proximal tibial epiphysis make it vulnerable to unique patterns of fractures.
Vitamin-D plays a vital role in bone homeostasis and its deficiency has an impact
on fracture risk and healing. We present the first ever reported case of
simultaneous bilateral proximal tibial physeal fractures in an athlete with
vitamin-D deficiency. Treatment consisted of plaster immobilisation, and the
patient made a full recovery and returned to preinjury level of activities. We
report this case for its uniqueness and as an educational review of the
importance of the developmental anatomy of the proximal tibia. We review the
literature and discuss how the stages of the growing physis determine the type of
fracture sustained.
PMID- 26425382
TI - Importance of NAB2-STAT6 Fusion in the Diagnosis of Pancreatic Solitary Fibrous
Tumor with Hamartoma-Like Features: A Case Report and Review of the Literature.
AB - We report a case of pancreatic hamartoma-like solitary fibrous tumor which was
differentiated from pancreatic hamartoma with the detection of NAB2-STAT6 fusion,
a specific mutation for solitary fibrous tumors. A pancreatic well-demarcated
solid nodule, 21 * 17 mm, of 82-year-old man was surgically enucleated.
Microscopic findings were close to a pancreatic hamartoma that consisted of
sparsely distributed pancreatic ducts and acini in heavily collagenized fibrous
stroma. Neither islet nor peripheral nerve existed in the tumor. The fibroblastic
cells in the stroma were immune-positive for CD34, CD99, and bcl-2. But these
expressions were not decisive in the differentiation between solitary fibrous
tumor and pancreatic hamartoma, because CD34 was positive for both tumors, and
CD99 and bcl-2 expressions were not elucidated in the previous cases of
pancreatic hamartomas. Thus, we evaluated NAB2-STAT6 fusion. The fibroblastic
cells were positive for STAT6 and sequencing analysis revealed the gene fusion
between NAB2 exon 4 and STAT6 exon 2, with which the final diagnos is of solitary
fibrous tumor was achieved. In conclusion, detection of NAB2-STAT6 fusion has a
great diagnostic value for pancreatic solitary fibrous tumors with hamartoma-like
features.
PMID- 26425383
TI - Neuroimaging Features of San Luis Valley Syndrome.
AB - A 14-month-old Hispanic female with a history of double-outlet right ventricle
and developmental delay in the setting of recombinant chromosome 8 syndrome was
referred for neurologic imaging. Brain MR revealed multiple abnormalities
primarily affecting midline structures, including commissural dysgenesis, vermian
and brainstem hypoplasia/dysplasia, an interhypothalamic adhesion, and an
epidermoid between the frontal lobes that enlarged over time. Spine MR
demonstrated hypoplastic C1 and C2 posterior elements, scoliosis, and a
borderline low conus medullaris position. Presented herein is the first
illustration of neuroimaging findings from a patient with San Luis Valley
syndrome.
PMID- 26425384
TI - THE FUNDAMENTAL SOLUTIONS FOR MULTI-TERM MODIFIED POWER LAW WAVE EQUATIONS IN A
FINITE DOMAIN.
AB - Fractional partial differential equations with more than one fractional
derivative term in time, such as the Szabo wave equation, or the power law wave
equation, describe important physical phenomena. However, studies of these multi
term time-space or time fractional wave equations are still under development. In
this paper, multi-term modified power law wave equations in a finite domain are
considered. The multi-term time fractional derivatives are defined in the Caputo
sense, whose orders belong to the intervals (1, 2], [2, 3), [2, 4) or (0, n) (n >
2), respectively. Analytical solutions of the multi-term modified power law wave
equations are derived. These new techniques are based on Luchko's Theorem, a
spectral representation of the Laplacian operator, a method of separating
variables and fractional derivative techniques. Then these general methods are
applied to the special cases of the Szabo wave equation and the power law wave
equation. These methods and techniques can also be extended to other kinds of the
multi-term time-space fractional models including fractional Laplacian.
PMID- 26425385
TI - Possible Benefit of Dietary Carnosine towards Depressive Disorders.
AB - Many stress-related and depressive disorders have been shown to be associated
with one or more of the following; shortened telomeres, raised cortisol levels
and increased susceptibility to age-related dysfunction. It is suggested here
that insufficient availability of the neurological peptide, carnosine, may
provide a biochemical link between stress- and depression-associated phenomena:
there is evidence that carnosine can enhance cortisol metabolism, suppress
telomere shortening and exert anti-aging activity in model systems. Dietary
supplementation with carnosine has been shown to suppress stress in animals, and
improve behaviour, cognition and well-being in human subjects. It is therefore
proposed that the therapeutic potential of carnosine dietary supplementation
towards stress-related and depressive disorders should be examined.
PMID- 26425387
TI - SUMOylation: Novel Neuroprotective Approach for Alzheimer's Disease?
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized
in the brain by the formation of amyloid-beta (Abeta)-containing plaques and
neurofibrillary tangles containing the microtubule-associated protein tau.
Neuroinflammation is another feature of AD and astrocytes are receiving
increasing attention as key contributors. Although some progress has been made,
the molecular mechanisms underlying the pathophysiology of AD remain unclear.
Interestingly, some of the main proteins involved in AD, including amyloid
precursor protein (APP) and tau, have recently been shown to be SUMOylated. The
post-translational modification by SUMO (small ubiquitin-like modifier) has been
shown to regulate APP and tau and may modulate other proteins implicated in AD.
Here we present an overview of recent studies suggesting that protein SUMOylation
might be involved in the underlying pathogenic mechanisms of AD and discuss how
this could be exploited for therapeutic intervention.
PMID- 26425386
TI - Metabolic Alterations Associated to Brain Dysfunction in Diabetes.
AB - From epidemiological studies it is known that diabetes patients display increased
risk of developing dementia. Moreover, cognitive impairment and Alzheimer's
disease (AD) are also accompanied by impaired glucose homeostasis and insulin
signalling. Although there is plenty of evidence for a connection between insulin
resistant diabetes and AD, definitive linking mechanisms remain elusive.
Cerebrovascular complications of diabetes, alterations in glucose homeostasis and
insulin signalling, as well as recurrent hypoglycaemia are the factors that most
likely affect brain function and structure. While difficult to study in patients,
the mechanisms by which diabetes leads to brain dysfunction have been
investigated in experimental models that display phenotypes of the disease. The
present article reviews the impact of diabetes and AD on brain structure and
function, and discusses recent findings from translational studies in animal
models that link insulin resistance to metabolic alterations that underlie brain
dysfunction. Such modifications of brain metabolism are likely to occur at early
stages of neurodegeneration and impact regional neurochemical profiles and
constitute non-invasive biomarkers detectable by magnetic resonance spectroscopy
(MRS).
PMID- 26425388
TI - The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease.
AB - Aging is a normal physiological process accompanied by cognitive decline. This
aging process has been the primary risk factor for development of aging-related
diseases such as Alzheimer's disease (AD). Cognitive deficit is related to
alterations of neurotrophic factors level such as brain-derived neurotrophic
factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic
factor (GDNF). These strong relationship between aging and AD is important to
investigate the time which they overlap, as well as, the pathophysiological
mechanism in each event. Considering that aging and AD are related to cognitive
impairment, here we discuss the involving these neurotrophic factors in the aging
process and AD.
PMID- 26425389
TI - Does Infection-Induced Immune Activation Contribute to Dementia?
AB - The central nervous system (CNS) is protected by a complex blood-brain barrier
system; however, a broad diversity of virus, bacteria, fungi, and protozoa can
gain access and cause illness. As pathogens replicate, they release molecules
that can be recognized by innate immune cells. These molecules are pathogen
associated molecular patterns (PAMP) and they are identified by pattern
recognition receptors (PRR) expressed on antigen-presenting cells. Examples of
PRR include toll-like receptors (TLR), receptors for advanced glycation
endproducts (RAGE), nucleotide binding oligomerisation domain (NOD)-like
receptors (NLR), c-type lectin receptors (CLR), RIG-I-like receptors (RLR), and
intra-cytosolic DNA sensors. The reciprocal action between PAMP and PRR triggers
the release of inflammatory mediators that regulate the elimination of invasive
pathogens. Damage-associated molecular patterns (DAMP) are endogenous
constituents released from damaged cells that also have the ability to activate
the innate immune response. An increase of RAGE expression levels on neurons,
astrocytes, microglia, and endothelial cells could be responsible for the
accumulation of alphabeta-amyloid in dementia and related to the chronic
inflammatory state that is found in neurodegenerative disorders.
PMID- 26425391
TI - Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders.
AB - Imidazole dipeptides (ID), such as carnosine (beta-alanyl-L-histidine), are
compounds widely distributed in excitable tissues of vertebrates. ID are also
endowed of several biochemical properties in biological tissues, including
antioxidant, bivalent metal ion chelating, proton buffering, and carbonyl
scavenger activities. Furthermore, remarkable biological effects have been
assigned to such compounds in age-related human disorders and in patients whose
activity of serum carnosinase is deficient or undetectable. Nevertheless, the
precise biological role of ID is still to be unraveled. In the present review we
shall discuss some evidences from clinical and basic studies for the utilization
of ID as a drug therapy for age-related human disorders.
PMID- 26425390
TI - Dopamine Receptors and Neurodegeneration.
AB - Dopamine (DA) is one of the major neurotransmitters and participates in a number
of functions such as motor coordination, emotions, memory, reward mechanism,
neuroendocrine regulation etc. DA exerts its effects through five DA receptors
that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2
like (D2, D3 and D4). All DA receptors are widely expressed in the central
nervous system (CNS) and play an important role in not only in physiological
conditions but also pathological scenarios. Abnormalities in the DAergic system
and its receptors in the basal ganglia structures are the basis Parkinson's
disease (PD), however DA also participates in other neurodegenerative disorders
such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological
conditions reorganization of DAergic system has been observed and most of the
times, those changes occur as a mechanism of compensation, but in some cases
contributes to worsening the alterations. Here we review the changes that occur
on DA transmission and DA receptors (DARs) at both levels expression and signals
transduction pathways as a result of neurotoxicity, inflammation and in
neurodegenerative processes. The better understanding of the role of DA receptors
in neuropathological conditions is crucial for development of novel therapeutic
approaches to treat alterations related to neurodegenerative diseases.
PMID- 26425393
TI - Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations.
AB - Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused
by the deficiency of phenylalanine hydroxylase. This deficiency leads to the
accumulation of Phe and its metabolites in tissues and body fluids of PKU
patients. The main signs and symptoms are found in the brain but the
pathophysiology of this disease is not well understood. In this context,
metabolic alterations such as oxidative stress, mitochondrial dysfunction, and
impaired protein and neurotransmitters synthesis have been described both in
animal models and patients. This review aims to discuss the main metabolic
disturbances reported in PKU and relate them with the pathophysiology of this
disease. The elucidation of the pathophysiology of brain damage found in PKU
patients will help to develop better therapeutic strategies to improve quality of
life of patients affected by this condition.
PMID- 26425395
TI - Astounding recovery after resection of an intradural nerve sheath tumor in an
adult male from Vietnam.
AB - BACKGROUND: Spinal cord tumors can be classified as intramedullary, intradural
extramedullary, or extradural. The differential diagnosis of spinal cord tumors
includes meningiomas, astrocytomas, ependymomas, metastasis, nerve sheath tumors
such as schwannomas or neurofibromas, and multiple sclerosis plaques. Radiology
can provide clues to the type of tumor, but a pathology evaluation of a specimen
is necessary to provide an accurate diagnosis. These tumors can cause a variety
of neurological symptoms from spinal cord compression including pain, weakness,
and paresthesia. They are treated by surgical resection, with a variety of
outcomes possible depending on the severity of the preoperative symptoms,
location and extent of the tumor, and efficacy of the surgery performed. CASE
DESCRIPTION: A 59-year-old male from Vietnam came to the Atlanta Medical Center
for evaluation of severe ride sided hemiparesis and paresthesias. He first
noticed alterations in his handwriting and quickly deteriorated to the point of
being unable to walk or move his right arm. A cervical spinal mass was identified
and analyzed on magnetic resonance imaging. Surgical resection was performed
under a microscope in a joint operation between an orthopedic surgeon and
neurosurgeon. A specimen of the tumor was sent to pathology for further
evaluation. CONCLUSION: The mass was determined to be an intradural
extramedullary schwannoma. The severity of the patient's symptoms and the
location and size of the tumor made full recovery unlikely and postoperative
quadriplegia a real possibility. The tumor was surgically resected, which led
surprisingly, however, to a full and prompt resolution of the patient's symptoms.
Less than 2 weeks after surgery, the patient was able to walk and had almost
fully regained use of his hands.
PMID- 26425394
TI - Potential Therapeutical Contributions of the Endocannabinoid System towards Aging
and Alzheimer's Disease.
AB - Aging can lead to decline in cognition, notably due to neurodegenerative
processes overwhelming the brain over time. As people live longer, numerous
concerns are rightfully raised toward long-term slowly incapacitating diseases
with no cure, such as Alzheimer's disease. Since the early 2000's, the role of
neuroinflammation has been scrutinized for its potential role in the development
of diverse neurodegenerative diseases notably because of its slow onset and
chronic nature in aging. Despite the lack of success yet, treatment of chronic
neuroinflammation could help alleviate process implicated in neurodegenerative
disease. A growing number of studies including our own have aimed at the
endocannabinoid system and unfolded unique effects of this system on
neuroinflammation, neurogenesis and hallmarks of Alzheimer's disease and made it
a reasonable target in the context of normal and pathological brain aging.
PMID- 26425392
TI - Mechanisms of Muscle Denervation in Aging: Insights from a Mouse Model of
Amyotrophic Lateral Sclerosis.
AB - Muscle denervation at the neuromuscular junction (NMJ) is thought to be a
contributing factor in age-related muscle weakness. Therefore, understanding the
mechanisms that modulate NMJ innervation is a key to developing therapies to
combat age-related muscle weakness affecting the elderly. Two mouse models, one
lacking the Cu/Zn superoxide dismutase (SOD1) gene and another harboring the
transgenic mutant human SOD1 gene, display progressive changes at the NMJ,
including muscle endplate fragmentation, nerve terminal sprouting, and
denervation. These changes at the NMJ share many of the common features observed
in the NMJs of aged mice. In this review, research findings demonstrating the
effects of PGC-1alpha, IGF-1, GDNF, MyoD, myogenin, and miR-206 on NMJ
innervation patterns in the G93A SOD1 mice will be highlighted in the context of
age-related muscle denervation.
PMID- 26425396
TI - A completely thrombosed, nongiant middle cerebral artery aneurysm mimicking an
intra-axial neoplasm.
AB - BACKGROUND: Few reports exist regarding thrombosed aneurysms where the initial
work up was concerning for a neoplasm. To date, no published reports exist
regarding a nongiant thrombosed middle cerebral artery aneurysm, where the
primary workup and treatment plan was directed toward a preliminary diagnosis of
intra-axial neoplasm. CASE DESCRIPTION: We report a 43-year-old female who
presented with a generalized tonic-clonic seizure attributed to a lesion along
the right superior temporal gyrus. The lesion enhanced on initial magnetic
resonance imaging (MRI) of the brain, as well as on follow-up MRI. Subsequent
vascular studies and metastatic work up were negative. A craniotomy with image
guidance was performed and an intraoperative diagnosis was made of a thrombosed
aneurysm along a branch of the middle cerebral artery. The aneurysm was trapped
and resected as there was no significant flow from the branch as seen on the
prior cerebral angiogram. The patient had an uneventful postoperative course.
CONCLUSION: Completely thrombosed, nongiant aneurysms can mimic an intra-axial
neoplasm. Typical imaging features for thrombosed aneurysms may be missed,
especially if the aneurysms are small, where imaging characteristics of the
intraluminal contents is more difficult to appreciate. Although imaging may be
consistent with a neoplastic lesion, there should be suspicion for a potential
underlying aneurysm.
PMID- 26425397
TI - Commentary on article: Laminoplasty versus laminectomy and fusion for multilevel
cervical myelopathy: A meta-analysis of clinical and radiological outcomes by
Chang-Hyun Lee et al.
AB - BACKGROUND: This is a commentary on the article laminoplasty versus laminectomy
and fusion (LF) for multilevel cervical myelopathy: A meta-analysis of clinical
and radiological outcomes by Chang-Hyun Lee et al. Here, the authors utilized
seven studies to compare the efficacy of cervical expansive laminoplasty (EL)
versus laminectomy and fusion (LF) to address three or more level multilevel
cervical spondylotic myelopathy (CSM). Both procedures led to similar degrees of
neurological recovery and short-term loss of lordosis, but found that LF led to
more favorable long-term results. METHODS: For patients with three or more level
CSM, laminectomy followed by an instrumented fusion (LF) has major advantages;
open bilateral decompression of the nerve roots, while minimizing the risk of
inadvertent injury to the cord, and the fusion's maintenance of lordosis.
RESULTS: Some would argue that inadvertent cord/root injury is greater utilizing
any of the EL techniques; e.g., unilateral, bilateral, or spinous process
splitting techniques. In short, why risk cord/root injury by manipulating the
compressive posterior/posterolateral elements, which are already threatening
neural function. CONCLUSION: Although the results of EL versus LF appeared
comparable in the short-term in these seven articles, LF resulted in better long
term outcomes. Some would also argue that LF, utilizing an open approach offers
safer bilateral neural exposure and decompression.
PMID- 26425398
TI - Unnecessary multiple epidural steroid injections delay surgery for massive lumbar
disc: Case discussion and review.
AB - BACKGROUND: Epidural steroid injections (ESI) in the lumbar spine are not
effective over the long-term for resolving "surgical" lesions. Here, we present a
patient with a massive L2-L3 lumbar disk herniation whose surgery was delayed for
4 months by multiple unnecessary ESI, resulting in a cauda equina syndrome.
METHODS: A 54-year-old male acutely developed increased low back and radiating
left leg pain in October of 2014. In December of 2014, a magnetic resonance
imaging (MRI) scan showed a massive central/left sided disk herniation at the L2
L3 level resulting in marked thecal sac and left L2 foraminal and L3 lateral
recess root compression. Despite the marked degree of neural compression, pain
management treated him with 3 ESI over the next 3 months. RESULTS: At the end of
April of 2015, he presented to spine surgeon with a cauda equina syndrome. When
the new MRI scan confirmed the previously documented massive central-left sided
L2-L3 disk herniation, the patient emergently underwent an L1-L3 laminectomy with
central-left sided L2-L3 lateral/foraminal diskectomy. Postoperatively, the
patient was neurologically intact. CONCLUSIONS: Pain specialists performed
multiple unnecessary lumbar ESI critically delaying spinal surgery for 4 months
in this patient with a massive lumbar disk herniation who ultimately developed a
cauda equina syndrome. Unfortunately, pain specialists (e.g., radiologists,
anesthesiologists, and physiatrists), not specifically trained to perform
neurological examinations or spinal surgery, are increasingly mismanaging spinal
disease with ESI/variants. It is time for spine surgeons to speak out against
this, and "take back" the care of patients with spinal surgical disease.
PMID- 26425399
TI - Synovial chondromatosis presenting as an epidural mass.
AB - BACKGROUND: Synovial chondromatosis is an uncommon disorder characterized by the
formation of multiple cartilaginous nodules in the synovium of the facet joint.
It most commonly affects large joints such as hip or shoulder. Commonly seen
features are bony erosion and calcifications. Synovial chondromatosis is rare in
the spine and there are few previous reports of extension into the spinal canal.
CASE DESCRIPTION: A 58-year-old man presented with a 2 year history of
progressive numbness in the right upper extremity without objective weakness. A
several month course of conservative management, including physical therapy,
failed to alleviate symptoms. Magnetic resonance imaging of the cervical spine
demonstrated the erosion of the right facet C5-C6 joint with listhesis and
foraminal enlargement secondary to a lesion. Treatment was offered to the patient
in the form of surgical resection. The lesion was removed in piecemeal fashion
using curettes and Cavitron ultrasonic surgical aspirator. Histological
examination demonstrated atypical well-differentiated cartilaginous
proliferation. CONCLUSION: This patient had an uncomplicated postoperative course
and experienced complete resolution of right upper extremity sensory symptoms.
Synovial chondromatosis may compromise cervical spinal cord and nerve roots if it
extends into the spinal canal. Although it remains rare, it should be included in
the differential diagnosis for upper extremity radiculopathy and myelopathy.
Surgical resection is a viable treatment option for symptomatic patients with
this pathology. In some cases, adequate resection may necessitate stabilization
with instrumentation.
PMID- 26425400
TI - Medicare payment data for spine reimbursement; important but flawed data for
evaluating utilization of resources.
AB - BACKGROUND: Medicare data showing physician-specific reimbursement for 2012 were
recently made public in the mainstream media. Given the ongoing interest in
containing healthcare costs, we analyze these data in the context of the delivery
of spinal surgery. METHODS: Demographics of 206 leading surgeons were extracted
including state, geographic area, residency training program, fellowship
training, and academic affiliation. Using current procedural terminology (CPT)
codes, information was evaluated regarding the number of lumbar laminectomies,
lumbar fusions, add-on laminectomy levels, and anterior cervical fusions
reimbursed by Medicare in 2012. RESULTS: In 2012 Medicare reimbursed the average
neurosurgeon slightly more than an orthopedic surgeon for all procedures
($142,075 vs. $110,920), but this was not found to be statistically significant
(P = 0.218). Orthopedic surgeons had a statistical trend illustrating increased
reimbursement for lumbar fusions specifically, $1187 versus $1073 (P = 0.07).
Fellowship trained spinal surgeons also, on average, received more from Medicare
($125,407 vs. $76,551), but again this was not statistically significant (P =
0.112). A surgeon in private practice, on average, was reimbursed $137,495 while
their academic counterparts were reimbursed $103,144 (P = 0.127). Surgeons
performing cervical fusions in the Centers for Disease Control West Region did
receive statistically significantly less reimbursement for that procedure then
those surgeons in other parts of the country (P = 0.015). Surgeons in the West
were reimbursed on average $849 for CPT code 22,551 while those in the Midwest
received $1475 per procedure. CONCLUSION: Medicare reimbursement data are
fundamentally flawed in determining healthcare expenditure as it shows a bias
toward delivery of care in specific patient demographics. However, neurosurgeons,
not just policy makers, must take ownership to analyze, investigate, and
interpret these data as it will affect healthcare reimbursement and delivery
moving forward.
PMID- 26425401
TI - Hospital Disaster Preparedness Tools: a Systematic Review.
AB - AIM: Evaluating hospital disaster preparedness is one the best ways for hospital
accreditation. The aim of this study was to evaluate the quality of outcome
measure that offer the level of measurement, reliability and validity that are
known as the ' psychometric properties' of the current hospital disaster
preparedness tools. METHODS: In total, 140 studies were retrieved. Studies which
had been published from 2000 to 2014 and had used hospital disaster preparedness
tools were appraised by using the PRISMA guideline. The content quality and the
quality of the psychometric properties of the retrieved tools were assessed by
using the World Health Organization Criteria for Hospital Preparedness as well as
the COSMIN criteria. FINDINGS: Only 33 studies met the inclusion criteria. In
total, eleven hospital disaster preparedness tools had been used in these 33
studies. These tools mainly focused on evaluating structural and non-structural
aspects of hospital preparedness and paid little attention, if any, to the key
functional aspect. CONCLUSION: Given the paramount importance of evaluating
hospital disaster preparedness and the weaknesses of current preparedness
evaluation tools, valid and reliable tools should be developed by using experts'
knowledge and experience through the processes of tool development and
psychometric evaluation.
PMID- 26425402
TI - The Effect of Transient Local Anti-inflammatory Treatment on the Survival of Pig
Retinal Progenitor Cell Allotransplants.
AB - PURPOSE: The development of photoreceptor replacement therapy for retinal
degenerative disorders requires the identification of the optimal cell source and
immunosuppressive regimen in a large animal model. Allotransplants are not
acutely rejected in swine subretinal space, although it is not known if survival
can be improved with immunosuppression. Here we investigated the survival and
integration of expanded pig retinal progenitor cells (pRPCs) in normal recipients
with and without transient anti-inflammatory suppression. METHODS: pRPCs were
derived from the neural retina of E60 GFP transgenic pigs, expanded for six
passages, characterized, and transplanted into the subretinal space of 12 pigs.
Six recipients received a single intravitreal injection of rapamycin and
dexamethasone. RESULTS: pRPCs expressed the photoreceptor development genes Sox2,
Pax6, Lhx2, Crx, Nrl, and Recoverin in vitro. Transplanted cells were identified
in 9 out of 12 recipients 4 weeks after the injection. pRPCs integrated primarily
into the photoreceptor inner segment layer and outer nuclear layer with single
cells present in the inner nuclear layer. Donor cells remained recoverin-positive
and acquired rhodopsin. We did not observe any signs of graft proliferation. The
immunosuppression did not affect the survival or distribution of grafts. No
macrophage infiltration or loss of retinal structure was observed in either
group. CONCLUSIONS: Local immunosuppression with rapamycin and dexamethasone does
not improve the outcome of pRPC allotransplantation into the subretinal space.
TRANSLATIONAL RELEVANCE: Survival and integration of pRPC together with the lack
of graft proliferation suggests that allogeneic RPC transplantation without
transient immunosuppression is a favorable approach for photoreceptor cell
replacement.
PMID- 26425403
TI - Diabetes Complications in Childhood Diabetes-New Biomarkers and Technologies.
AB - A major challenge in preventing vascular complications in diabetes is the
inability to identify high-risk patients at an early stage, emphasizing the
importance of discovering new risk factors, technologies and therapeutic targets
to reduce the development and progression of complications. Promising biomarkers
which may improve risk stratification and serve as therapeutic targets, include:
uric acid, insulin sensitivity, copeptin, SGLT-2 and Klotho/FGF-23. Non-invasive
measures of macrovasuclar disease in youth, include: 1) pulse wave velocity to
examine arterial stiffness; 2) carotid intima-media thickness to evaluate
arterial thickness; 3) cardiac MRI to investigate cardiac function and structure.
Novel microvascular measures include: GFR by iohexol clearance using filter paper
to directly measure GFR, retinal vascular geometry to predict early retinal
changes and corneal confocal microscopy to improve detection of early nerve loss
to better predict diabetic neuropathy. Herein we will review technologies, novel
biomarkers, and therapeutic targets in relation to vascular complications of
diabetes.
PMID- 26425404
TI - Formation of pure Cu nanocrystals upon post-growth annealing of Cu-C material
obtained from focused electron beam induced deposition: comparison of different
methods.
AB - In this paper we study in detail the post-growth annealing of a copper-containing
material deposited with focused electron beam induced deposition (FEBID). The
organometallic precursor Cu(II)(hfac)2 was used for deposition and the results
were compared to that of compared to earlier experiments with (hfac)Cu(I)(VTMS)
and (hfac)Cu(I)(DMB). Transmission electron microscopy revealed the deposition of
amorphous material from Cu(II)(hfac)2. In contrast, as-deposited material from
(hfac)Cu(I)(VTMS) and (hfac)Cu(I)(DMB) was nano-composite with Cu nanocrystals
dispersed in a carbonaceous matrix. After annealing at around 150-200 degrees C
all deposits showed the formation of pure Cu nanocrystals at the outer surface of
the initial deposit due to the migration of Cu atoms from the carbonaceous matrix
containing the elements carbon, oxygen, and fluorine. Post-irradiation of
deposits with 200 keV electrons in a transmission electron microscope favored the
formation of Cu nanocrystals within the carbonaceous matrix of freestanding rods
and suppressed the formation on their surface. Electrical four-point measurements
on FEBID lines from Cu(hfac)2 showed five orders of magnitude improvement in
conductivity when being annealed conventionally and by laser-induced heating in
the scanning electron microscope chamber.
PMID- 26425405
TI - Continuum models of focused electron beam induced processing.
AB - Focused electron beam induced processing (FEBIP) is a suite of direct-write, high
resolution techniques that enable fabrication and editing of nanostructured
materials inside scanning electron microscopes and other focused electron beam
(FEB) systems. Here we detail continuum techniques that are used to model FEBIP,
and release software that can be used to simulate a wide range of processes
reported in the FEBIP literature. These include: (i) etching and deposition
performed using precursors that interact with a surface through physisorption and
activated chemisorption, (ii) gas mixtures used to perform simultaneous focused
electron beam induced etching and deposition (FEBIE and FEBID), and (iii) etch
processes that proceed through multiple reaction pathways and generate a number
of reaction products at the substrate surface. We also review and release
software for Monte Carlo modeling of the precursor gas flux which is needed as an
input parameter for continuum FEBIP models.
PMID- 26425406
TI - Possibilities and limitations of advanced transmission electron microscopy for
carbon-based nanomaterials.
AB - A major revolution for electron microscopy in the past decade is the introduction
of aberration correction, which enables one to increase both the spatial
resolution and the energy resolution to the optical limit. Aberration correction
has contributed significantly to the imaging at low operating voltages. This is
crucial for carbon-based nanomaterials which are sensitive to electron
irradiation. The research of carbon nanomaterials and nanohybrids, in particular
the fundamental understanding of defects and interfaces, can now be carried out
in unprecedented detail by aberration-corrected transmission electron microscopy
(AC-TEM). This review discusses new possibilities and limits of AC-TEM at low
voltage, including the structural imaging at atomic resolution, in three
dimensions and spectroscopic investigation of chemistry and bonding. In situ TEM
of carbon-based nanomaterials is discussed and illustrated through recent reports
with particular emphasis on the underlying physics of interactions between
electrons and carbon atoms.
PMID- 26425407
TI - Electrical properties and mechanical stability of anchoring groups for single
molecule electronics.
AB - We report on an experimental investigation of transport through single molecules,
trapped between two gold nano-electrodes fabricated with the mechanically
controlled break junction (MCBJ) technique. The four molecules studied share the
same core structure, namely oligo(phenylene ethynylene) (OPE3), while having
different aurophilic anchoring groups: thiol (SAc), methyl sulfide (SMe), pyridyl
(Py) and amine (NH2). The focus of this paper is on the combined characterization
of the electrical and mechanical properties determined by the anchoring groups.
From conductance histograms we find that thiol anchored molecules provide the
highest conductance; a single-level model fit to current-voltage characteristics
suggests that SAc groups exhibit a higher electronic coupling to the electrodes,
together with better level alignment than the other three groups. An analysis of
the mechanical stability, recording the lifetime in a self-breaking method, shows
that Py and SAc yield the most stable junctions while SMe form short-lived
junctions. Density functional theory combined with non-equlibrium Green's
function calculations help in elucidating the experimental findings.
PMID- 26425410
TI - How decision analysis can further nanoinformatics.
AB - The increase in nanomaterial research has resulted in increased nanomaterial
data. The next challenge is to meaningfully integrate and interpret these data
for better and more efficient decisions. Due to the complex nature of
nanomaterials, rapid changes in technology, and disunified testing and data
publishing strategies, information regarding material properties is often
illusive, uncertain, and/or of varying quality, which limits the ability of
researchers and regulatory agencies to process and use the data. The vision of
nanoinformatics is to address this problem by identifying the information
necessary to support specific decisions (a top-down approach) and collecting and
visualizing these relevant data (a bottom-up approach). Current nanoinformatics
efforts, however, have yet to efficiently focus data acquisition efforts on the
research most relevant for bridging specific nanomaterial data gaps. Collecting
unnecessary data and visualizing irrelevant information are expensive activities
that overwhelm decision makers. We propose that the decision analytic techniques
of multicriteria decision analysis (MCDA), value of information (VOI), weight of
evidence (WOE), and portfolio decision analysis (PDA) can bridge the gap from
current data collection and visualization efforts to present information relevant
to specific decision needs. Decision analytic and Bayesian models could be a
natural extension of mechanistic and statistical models for nanoinformatics
practitioners to master in solving complex nanotechnology challenges.
PMID- 26425408
TI - Influence of surface chemical properties on the toxicity of engineered zinc oxide
nanoparticles to embryonic zebrafish.
AB - Zinc oxide nanoparticles (ZnO NPs) are widely used in a variety of products, thus
understanding their health and environmental impacts is necessary to
appropriately manage their risks. To keep pace with the rapid increase in
products utilizing engineered ZnO NPs, rapid in silico toxicity test methods
based on knowledge of comprehensive in vivo and in vitro toxic responses are
beneficial in determining potential nanoparticle impacts. To achieve or enhance
their desired function, chemical modifications are often performed on the NPs
surface; however, the roles of these alterations play in determining the toxicity
of ZnO NPs are still not well understood. As such, we investigated the toxicity
of 17 diverse ZnO NPs varying in both size and surface chemistry to developing
zebrafish (exposure concentrations ranging from 0.016 to 250 mg/L). Despite
assessing a suite of 19 different developmental, behavioural and morphological
endpoints in addition to mortality in this study, mortality was the most common
endpoint observed for all of the ZnO NP types tested. ZnO NPs with surface
chemical modification, regardless of the type, resulted in mortality at 24 hours
post-fertilization (hpf) while uncoated particles did not induce significant
mortality until 120 hpf. Using eight intrinsic chemical properties that relate to
the outermost surface chemistry of the engineered ZnO nanoparticles, the highly
dimensional toxicity data were converted to a 2-dimensional data set through
principal component analysis (PCA). Euclidean distance was used to partition
different NPs into several groups based on converted data (score) which were
directly related to changes in the outermost surface chemistry. Kriging
estimations were then used to develop a contour map based on mortality data as a
response. This study illustrates how the intrinsic properties of NPs, including
surface chemical modifications and capping agents, are useful to separate and
identify ZnO NP toxicity to zebrafish (Danio rerio).
PMID- 26425409
TI - Experiences in supporting the structured collection of cancer nanotechnology data
using caNanoLab.
AB - The cancer Nanotechnology Laboratory (caNanoLab) data portal is an online
nanomaterial database that allows users to submit and retrieve information on
well-characterized nanomaterials, including composition, in vitro and in vivo
experimental characterizations, experimental protocols, and related publications.
Initiated in 2006, caNanoLab serves as an established resource with an
infrastructure supporting the structured collection of nanotechnology data to
address the needs of the cancer biomedical and nanotechnology communities. The
portal contains over 1,000 curated nanomaterial data records that are publicly
accessible for review, comparison, and re-use, with the ultimate goal of
accelerating the translation of nanotechnology-based cancer therapeutics,
diagnostics, and imaging agents to the clinic. In this paper, we will discuss
challenges associated with developing a nanomaterial database and recognized
needs for nanotechnology data curation and sharing in the biomedical research
community. We will also describe the latest version of caNanoLab, caNanoLab 2.0,
which includes enhancements and new features to improve usability such as
personalized views of data and enhanced search and navigation.
PMID- 26425411
TI - Materials for sustainable energy production, storage, and conversion.
PMID- 26425412
TI - Simple and efficient way of speeding up transmission calculations with k-point
sampling.
AB - The transmissions as functions of energy are central for electron or phonon
transport in the Landauer transport picture. We suggest a simple and
computationally "cheap" post-processing scheme to interpolate transmission
functions over k-points to get smooth well-converged average transmission
functions. This is relevant for data obtained using typical "expensive" first
principles calculations where the leads/electrodes are described by periodic
boundary conditions. We show examples of transport in graphene structures where a
speed-up of an order of magnitude is easily obtained.
PMID- 26425413
TI - The eNanoMapper database for nanomaterial safety information.
AB - BACKGROUND: The NanoSafety Cluster, a cluster of projects funded by the European
Commision, identified the need for a computational infrastructure for
toxicological data management of engineered nanomaterials (ENMs). Ontologies,
open standards, and interoperable designs were envisioned to empower a harmonized
approach to European research in nanotechnology. This setting provides a number
of opportunities and challenges in the representation of nanomaterials data and
the integration of ENM information originating from diverse systems. Within this
cluster, eNanoMapper works towards supporting the collaborative safety assessment
for ENMs by creating a modular and extensible infrastructure for data sharing,
data analysis, and building computational toxicology models for ENMs. RESULTS:
The eNanoMapper database solution builds on the previous experience of the
consortium partners in supporting diverse data through flexible data storage,
open source components and web services. We have recently described the design of
the eNanoMapper prototype database along with a summary of challenges in the
representation of ENM data and an extensive review of existing nano-related data
models, databases, and nanomaterials-related entries in chemical and
toxicogenomic databases. This paper continues with a focus on the database
functionality exposed through its application programming interface (API), and
its use in visualisation and modelling. Considering the preferred community
practice of using spreadsheet templates, we developed a configurable spreadsheet
parser facilitating user friendly data preparation and data upload. We further
present a web application able to retrieve the experimental data via the API and
analyze it with multiple data preprocessing and machine learning algorithms.
CONCLUSION: We demonstrate how the eNanoMapper database is used to import and
publish online ENM and assay data from several data sources, how the
"representational state transfer" (REST) API enables building user friendly
interfaces and graphical summaries of the data, and how these resources
facilitate the modelling of reproducible quantitative structure-activity
relationships for nanomaterials (NanoQSAR).
PMID- 26425414
TI - Analysis of soil bacteria susceptibility to manufactured nanoparticles via data
visualization.
AB - The impact of ZnO and TiO2 manufactured nanoparticles (MNPs) on soil bacterial
communities for different exposure periods and MNP doses was explored via data
visualization techniques. Interrelationships between MNP treatments and responses
of bacterial taxa were illustrated by bipartite graphs, allowing fast
identification of important soil bacterial taxa that are susceptible to MNPs.
Contribution biplots with subcompositional coherence property were generated via
log-ratio analysis (LRA), which jointly display the treatment distribution and
the variance (contribution) of bacterial taxa. The LRA contribution biplots and
nonmetric multi-dimensional scaling (NMDS) of the dataset, along with
hierarchical clustering, demonstrated that high doses of ZnO and TiO2 MNPs caused
significant compositional changes in soil bacterial communities. The suitability
of family level for MNP taxonomic impact assessment was demonstrated by both the
LRA biplots and simplified NMDSs with quantification provided by the distance
correlation between MNP impacts summarized at different taxonomic levels. The
present study demonstrates that visual exploration could potentially assist in
knowledge discovery and interpretation of data on soil bacterial communities
exposed to MNPs and thus evaluate the potential for environmental impacts.
PMID- 26425415
TI - Structural and magnetic properties of iron nanowires and iron nanoparticles
fabricated through a reduction reaction.
AB - The main goal of this work is to study the structural and magnetic properties of
iron nanowires and iron nanoparticles, which have been fabricated in almost the
same processes. The only difference in the synthesis is an application of an
external magnetic field in order to form the iron nanowires. Both nanomaterials
have been examined by means of transmission electron microscopy, energy
dispersive X-ray spectrometry, X-ray diffractometry and Mossbauer spectrometry to
determine their structures. Structural investigations confirm that obtained iron
nanowires as well as nanoparticles reveal core-shell structures and they are
composed of crystalline iron cores that are covered by amorphous or highly
defected phases of iron and iron oxides. Magnetic properties have been measured
using a vibrating sample magnetometer. The obtained values of coercivity,
remanent magnetization, saturation magnetization as well as Curie temperature
differ for both studied nanostructures. Higher values of magnetizations are
observed for iron nanowires. At the same time, coercivity and Curie temperature
are higher for iron nanoparticles.
PMID- 26425416
TI - In situ SU-8 silver nanocomposites.
AB - Nanocomposite materials containing metal nanoparticles are of considerable
interest in photonics and optoelectronics applications. However, device
fabrication of such materials always encounters the challenge of incorporation of
preformed nanoparticles into photoresist materials. As a solution to this
problem, an easy new method of fabricating silver nanocomposites by an in situ
reduction of precursors within the epoxy-based photoresist SU-8 has been
developed. AgNO3 dissolved in acetonitrile and mixed with the epoxy-based
photoresist SU-8 forms silver nanoparticles primarily during the pre- and post
exposure soft bake steps at 95 degrees C. A further high-temperature treatment
at 300 degrees C resulted in the formation of densely homogeneously distributed
silver nanoparticles in the photoresist matrix. No particle growth or
agglomeration of nanoparticles is observed at this point. The reported new in
situ silver nanocomposite materials can be spin coated as homogeneous thin films
and structured by using UV lithography. A resolution of 5 um is achieved in the
lithographic process. The UV exposure time is found to be independent of the
nanoparticle concentration. The fabricated silver nanocomposites exhibit high
plasmonic responses suitable for the development of new optoelectronic and
optical sensing devices.
PMID- 26425417
TI - Analyzing collaboration networks and developmental patterns of nano-enabled drug
delivery (NEDD) for brain cancer.
AB - The rapid development of new and emerging science & technologies (NESTs) brings
unprecedented challenges, but also opportunities. In this paper, we use
bibliometric and social network analyses, at country, institution, and individual
levels, to explore the patterns of scientific networking for a key nano area -
nano-enabled drug delivery (NEDD). NEDD has successfully been used clinically to
modulate drug release and to target particular diseased tissues. The data for
this research come from a global compilation of research publication information
on NEDD directed at brain cancer. We derive a family of indicators that address
multiple facets of research collaboration and knowledge transfer patterns.
Results show that: (1) international cooperation is increasing, but networking
characteristics change over time; (2) highly productive institutions also lead in
influence, as measured by citation to their work, with American institutes
leading; (3) research collaboration is dominated by local relationships, with
interesting information available from authorship patterns that go well beyond
journal impact factors. Results offer useful technical intelligence to help
researchers identify potential collaborators and to help inform R&D management
and science & innovation policy for such nanotechnologies.
PMID- 26425418
TI - Synthesis, characterization and in vitro biocompatibility study of Au/TMC/Fe3O4
nanocomposites as a promising, nontoxic system for biomedical applications.
AB - The unique properties and applications of iron oxide and Au nanoparticles have
motivated researchers to synthesize and optimize a combined nanocomposite
containing both. By using various polymers such as chitosan, some of the problems
of classic core-shell structures (such as reduced saturation magnetization and
thick coating) have been overcome. In the present study, chitosan and one of its
well-known derivatives, N-trimethylchitosan (TMC), were applied to construct
three-layer nanocomposites in an Au/polymer/Fe3O4 system. It was demonstrated
that replacement of chitosan with TMC reasonably improved the properties of the
final nanocomposites including their size, magnetic behavior and thermal
stability. Moreover, the results of the MTT assay showed no significant
cytotoxicity effect when the Au/TMC/Fe3O4 nanocomposites were applied in vitro.
These TMC-containing magnetic nanoparticles are well-coated by Au nanoparticles
and have good biocompatibility and can thus play the role of a platform or a
label in various fields of application, especially the biomedical sciences and
biosensors.
PMID- 26425420
TI - Towards multifunctional inorganic materials: biopolymeric templates.
PMID- 26425419
TI - Conductance through single biphenyl molecules: symmetric and asymmetric coupling
to electrodes.
AB - The contacts and the chemical bonds formed between metallic electrodes and
molecules determine to a large extent the conductive properties of single
molecular junctions, which represent the smallest possible active elements in an
electronic circuit. We therefore investigated in a comparative study, using the
break junction technique (MCBJ), the conductive properties of [1,1'-biphenyl]
4,4'-dithiol (M1) and of 4'-mercapto-[1,1'-biphenyl]-4-carbonitrile (M2) between
gold electrodes. As a function of electrode separation, characterized by the
conductance close to 0 V, we found several plateaus of relative stability, with
those close to 0.01G0 being the most pronounced. The overall conductance of
symmetric and asymmetric molecules were surprisingly similar, only the range of
stability was smaller for M2. While M1 yielded symmetric I-V-curves, only small
asymmetries were detected for M2. These are also reflected in the comparable
values for coupling parameters using the single level resonance model. The high
conductance for the asymmetric molecule is interpreted as a result of coherent
coupling of electronic states through the whole molecule, so that the outcome
cannot be predicted just by adding conductive properties of individual molecular
groups.
PMID- 26425421
TI - Radiation losses in the microwave Ku band in magneto-electric nanocomposites.
AB - A study on radiation losses in conducting polymer nanocomposites, namely La-Co
substituted barium hexaferrite and polyaniline, is presented. The study was
performed by means of a vector network analyser, X-ray diffraction, Fourier
transform infrared spectroscopy, transmission electron microscopy, electron spin
resonance spectroscopy and a vibrating sample magnetometer. It is found that the
maximum loss occurs at 17.9 GHz (-23.10 dB, 99% loss) which is due to the
composition of a conducting polymer and a suitable magnetic material. A
significant role of polyaniline has been observed in ESR. The influence of the
magnetic properties on the radiation losses is explained. Further studies
revealed that the prepared material is a nanocomposite. FTIR spectra show the
presence of expected chemical structures such as C-H bonds in a ring system at
1512 cm(-1).
PMID- 26425423
TI - Imaging of carbon nanomembranes with helium ion microscopy.
AB - Carbon nanomembranes (CNMs) prepared from aromatic self-assembled monolayers
constitute a recently developed class of 2D materials. They are made by a
combination of self-assembly, radiation-induced cross-linking and the detachment
of the cross-linked SAM from its substrate. CNMs can be deposited on arbitrary
substrates, including holey and perforated ones, as well as on metallic
(transmission electron microscopy) grids. Therewith, freestanding membranes with
a thickness of 1 nm and macroscopic lateral dimensions can be prepared. Although
free-standing CNMs cannot be imaged by light microscopy, charged particle
techniques can visualize them. However, CNMs are electrically insulating, which
makes them sensitive to charging. We demonstrate that the helium ion microscope
(HIM) is a good candidate for imaging freestanding CNMs due to its efficient
charge compensation tool. Scanning with a beam of helium ions while recording the
emitted secondary electrons generates the HIM images. The advantages of HIM are
high resolution, high surface sensitivity and large depth of field. The effects
of sample charging, imaging of multilayer CNMs as well as imaging artefacts are
discussed.
PMID- 26425422
TI - Atomic scale interface design and characterisation.
PMID- 26425424
TI - Lower nanometer-scale size limit for the deformation of a metallic glass by shear
transformations revealed by quantitative AFM indentation.
AB - We combine non-contact atomic force microscopy (AFM) imaging and AFM indentation
in ultra-high vacuum to quantitatively and reproducibly determine the hardness
and deformation mechanisms of Pt(111) and a Pt57.5Cu14.7Ni5.3P22.5 metallic glass
with unprecedented spatial resolution. Our results on plastic deformation
mechanisms of crystalline Pt(111) are consistent with the discrete mechanisms
established for larger scales: Plasticity is mediated by dislocation gliding and
no rate dependence is observed. For the metallic glass we have discovered that
plastic deformation at the nanometer scale is not discrete but continuous and
localized around the indenter, and does not exhibit rate dependence. This
contrasts with the observation of serrated, rate-dependent flow of metallic
glasses at larger scales. Our results reveal a lower size limit for metallic
glasses below which shear transformation mechanisms are not activated by
indentation. In the case of metallic glass, we conclude that the energy stored in
the stressed volume during nanometer-scale indentation is insufficient to account
for the interfacial energy of a shear band in the glassy matrix.
PMID- 26425425
TI - A simple method for the determination of qPlus sensor spring constants.
AB - qPlus sensors are widely used to measure forces at the atomic scale, however,
confidence in these measurements is limited by inconsistent reports of the spring
constant of the sensor and complications from finite tip heights. Here we combine
a numerical investigation of the force reconstruction with an experimental
characterization of the flexural mechanics of the qPlus sensor. Numerical studies
reveal significant errors in reconstructed force for tip heights exceeding 400
MUm or one sixth of the cantilever length. Experimental results with a calibrated
nanoindenter reveal excellent agreement with an Euler-Bernoulli beam model for
the sensor. Prior to the attachment of a tip, measured spring constants of 1902
+/- 29 N/m are found to be in agreement with theoretical predictions for the
geometry and material properties of the sensor once a peaked ridge in the beam
cross section is included. We further develop a correction necessary to adjust
the spring constant for the size and placement of the tip.
PMID- 26425426
TI - A facile method for the preparation of bifunctional Mn:ZnS/ZnS/Fe3O4 magnetic and
fluorescent nanocrystals.
AB - Bifunctional magnetic and fluorescent core/shell/shell Mn:ZnS/ZnS/Fe3O4
nanocrystals were synthesized in a basic aqueous solution using 3
mercaptopropionic acid (MPA) as a capping ligand. The structural and optical
properties of the heterostructures were characterized by X-ray diffraction (XRD),
dynamic light scattering (DLS), transmission electron microscopy (TEM), UV-vis
spectroscopy and photoluminescence (PL) spectroscopy. The PL spectra of
Mn:ZnS/ZnS/Fe3O4 quantum dots (QDs) showed marked visible emission around 584 nm
related to the (4)T1 -> (6)A1 Mn(2+) transition. The PL quantum yield (QY) and
the remnant magnetization can be regulated by varying the thickness of the
magnetic shell. The results showed that an increase in the thickness of the Fe3O4
magnetite layer around the Mn:ZnS/ZnS core reduced the PL QY but improved the
magnetic properties of the composites. Nevertheless, a good compromise was
achieved in order to maintain the dual modality of the nanocrystals, which may be
promising candidates for various biological applications.
PMID- 26425427
TI - The Nanomaterial Data Curation Initiative: A collaborative approach to assessing,
evaluating, and advancing the state of the field.
AB - The Nanomaterial Data Curation Initiative (NDCI), a project of the National
Cancer Informatics Program Nanotechnology Working Group (NCIP NanoWG), explores
the critical aspect of data curation within the development of informatics
approaches to understanding nanomaterial behavior. Data repositories and tools
for integrating and interrogating complex nanomaterial datasets are gaining
widespread interest, with multiple projects now appearing in the US and the EU.
Even in these early stages of development, a single common aspect shared across
all nanoinformatics resources is that data must be curated into them. Through
exploration of sub-topics related to all activities necessary to enable, execute,
and improve the curation process, the NDCI will provide a substantive analysis of
nanomaterial data curation itself, as well as a platform for multiple other
important discussions to advance the field of nanoinformatics. This article
outlines the NDCI project and lays the foundation for a series of papers on
nanomaterial data curation. The NDCI purpose is to: 1) present and evaluate the
current state of nanomaterial data curation across the field on multiple specific
data curation topics, 2) propose ways to leverage and advance progress for both
individual efforts and the nanomaterial data community as a whole, and 3) provide
opportunities for similar publication series on the details of the interactive
needs and workflows of data customers, data creators, and data analysts. Initial
responses from stakeholder liaisons throughout the nanoinformatics community
reveal a shared view that it will be critical to focus on integration of datasets
with specific orientation toward the purposes for which the individual resources
were created, as well as the purpose for integrating multiple resources. Early
acknowledgement and undertaking of complex topics such as uncertainty,
reproducibility, and interoperability is proposed as an important path to
addressing key challenges within the nanomaterial community, such as reducing
collateral negative impacts and decreasing the time from development to market
for this new class of technologies.
PMID- 26425428
TI - Template-controlled mineralization: Determining film granularity and structure by
surface functionality patterns.
AB - We present a promising first example towards controlling the properties of a self
assembling mineral film by means of the functionality and polarity of a substrate
template. In the presented case, a zinc oxide film is deposited by chemical bath
deposition on a nearly topography-free template structure composed of a pattern
of two self-assembled monolayers with different chemical functionality. We
demonstrate the template-modulated morphological properties of the growing film,
as the surface functionality dictates the granularity of the growing film. This,
in turn, is a key property influencing other film properties such as
conductivity, piezoelectric activity and the mechanical properties. A very
pronounced contrast is observed between areas with an underlying fluorinated, low
energy template surface, showing a much more (almost two orders of magnitude)
coarse-grained film with a typical agglomerate size of around 75 nm. In contrast,
amino-functionalized surface areas induce the growth of a very smooth, fine
grained surface with a roughness of around 1 nm. The observed influence of the
template on the resulting clear contrast in morphology of the growing film could
be explained by a contrast in surface adhesion energies and surface diffusion
rates of the nanoparticles, which nucleate in solution and subsequently deposit
on the functionalized substrate.
PMID- 26425429
TI - Nanotechnology in the real world: Redeveloping the nanomaterial consumer products
inventory.
AB - To document the marketing and distribution of nano-enabled products into the
commercial marketplace, the Woodrow Wilson International Center for Scholars and
the Project on Emerging Nanotechnologies created the Nanotechnology Consumer
Products Inventory (CPI) in 2005. The objective of this present work is to
redevelop the CPI by leading a research effort to increase the usefulness and
reliability of this inventory. We created eight new descriptors for consumer
products, including information pertaining to the nanomaterials contained in each
product. The project was motivated by the recognition that a diverse group of
stakeholders from academia, industry, and state/federal government had become
highly dependent on the inventory as an important resource and bellweather of the
pervasiveness of nanotechnology in society. We interviewed 68 nanotechnology
experts to assess key information needs. Their answers guided inventory
modifications by providing a clear conceptual framework best suited for user
expectations. The revised inventory was released in October 2013. It currently
lists 1814 consumer products from 622 companies in 32 countries. The Health and
Fitness category contains the most products (762, or 42% of the total). Silver is
the most frequently used nanomaterial (435 products, or 24%); however, 49% of the
products (889) included in the CPI do not provide the composition of the
nanomaterial used in them. About 29% of the CPI (528 products) contain
nanomaterials suspended in a variety of liquid media and dermal contact is the
most likely exposure scenario from their use. The majority (1288 products, or
71%) of the products do not present enough supporting information to corroborate
the claim that nanomaterials are used. The modified CPI has enabled crowdsourcing
capabilities, which allow users to suggest edits to any entry and permits
researchers to upload new findings ranging from human and environmental exposure
data to complete life cycle assessments. There are inherent limitations to this
type of database, but these modifications to the inventory addressed the majority
of criticisms raised in published literature and in surveys of nanotechnology
stakeholders and experts. The development of standardized methods and metrics for
nanomaterial characterization and labelling in consumer products can lead to
greater understanding between the key stakeholders in nanotechnology, especially
consumers, researchers, regulators, and industry.
PMID- 26425430
TI - Nonlinear optical properties of near-infrared region Ag2S quantum dots pumped by
nanosecond laser pulses.
AB - This study investigates near-infrared region Ag2S quantum dots (QDs) and their
nonlinear optical response under 532 nm nanosecond laser pulses. Our experimental
result shows that nonlinear transmission is reduced from 0.084 to 0.04. The
observed narrowing behavior of the output pulse width shows superior optical
limiting. We discuss the physical mechanisms responsible for the nonlinear
optical response of the QDs. The average size of the nanocrystals was 5.5 nm. Our
results suggest the possibility of using these Ag2S QDs for photoelectric,
biosensor, optical ranging, and self-adaptive technologies.
PMID- 26425432
TI - Surface engineering of nanoporous substrate for solid oxide fuel cells with
atomic layer-deposited electrolyte.
AB - Solid oxide fuel cells with atomic layer-deposited thin film electrolytes
supported on anodic aluminum oxide (AAO) are electrochemically characterized with
varying thickness of bottom electrode catalyst (BEC); BECs which are 0.5 and 4
times thicker than the size of AAO pores are tested. The thicker BEC ensures far
more active mass transport on the BEC side and resultantly the thicker BEC cell
generates ~11 times higher peak power density than the thinner BEC cell at 500
degrees C.
PMID- 26425433
TI - Two-phase equilibrium states in individual Cu-Ni nanoparticles: size, depletion
and hysteresis effects.
AB - In isolated bimetallic nanoscale systems the limit amount of matter and surface
induced size effects can change the thermodynamics of first-order phase
transformation. In this paper we present theoretical modification of Gibbs free
energy concept describing first-order phase transformation of binary alloyed
nanoparticles taking into account size effects as well as depletion and
hysteresis effects. In such a way the hysteresis in a form of nonsymmetry for
forth and back transforming paths takes place; compositional splitting and the
loops-like splitted path on the size dependent temperature-composition phase
diagram occur. Our calculations for individual Cu-Ni nanoparticle show that one
must differentiate the solubility curves and the equilibrium loops (discussed
here in term of solidification and melting loops). For the first time we have
calculated and present here on the temperature-composition phase diagram the
nanomelting loop at the size of 80 nm and the nanosolidification loop at the size
of 25 nm for an individual Cu-Ni nanoparticle. So we observe the difference
between the size-dependent phase diagram and solubility diagram, between two
phase equilibrium curves and solubility curves; also intersection of nanoliquidus
and nanosolidus is available. These findings lead to the necessity to reconsider
such basic concepts in materials science as phase diagram and solubility diagram.
PMID- 26425434
TI - Metal hydrides: an innovative and challenging conversion reaction anode for
lithium-ion batteries.
AB - The state of the art of conversion reactions of metal hydrides (MH) with lithium
is presented and discussed in this review with regard to the use of these
hydrides as anode materials for lithium-ion batteries. A focus on the gravimetric
and volumetric storage capacities for different examples from binary, ternary and
complex hydrides is presented, with a comparison between thermodynamic prediction
and experimental results. MgH2 constitutes one of the most attractive metal
hydrides with a reversible capacity of 1480 mA.h.g(-1) at a suitable potential
(0.5 V vs Li(+)/Li(0)) and the lowest electrode polarization (<0.2 V) for
conversion materials. Conversion process reaction mechanisms with lithium are
subsequently detailed for MgH2, TiH2, complex hydrides Mg2MH x and other Mg-based
hydrides. The reversible conversion reaction mechanism of MgH2, which is lithium
controlled, can be extended to others hydrides as: MH x + xLi(+) + xe(-) in
equilibrium with M + xLiH. Other reaction paths-involving solid solutions,
metastable distorted phases, and phases with low hydrogen content-were recently
reported for TiH2 and Mg2FeH6, Mg2CoH5 and Mg2NiH4. The importance of fundamental
aspects to overcome technological difficulties is discussed with a focus on
conversion reaction limitations in the case of MgH2. The influence of MgH2
particle size, mechanical grinding, hydrogen sorption cycles, grinding with
carbon, reactive milling under hydrogen, and metal and catalyst addition to the
MgH2/carbon composite on kinetics improvement and reversibility is presented.
Drastic technological improvement in order to the enhance conversion process
efficiencies is needed for practical applications. The main goals are minimizing
the impact of electrode volume variation during lithium extraction and overcoming
the poor electronic conductivity of LiH. To use polymer binders to improve the
cycle life of the hydride-based electrode and to synthesize nanoscale composite
hydride can be helpful to address these drawbacks. The development of high
capacity hydride anodes should be inspired by the emergent nano-research
prospects which share the knowledge of both hydrogen-storage and lithium-anode
communities.
PMID- 26425431
TI - NanoE-Tox: New and in-depth database concerning ecotoxicity of nanomaterials.
AB - The increasing production and use of engineered nanomaterials (ENMs) inevitably
results in their higher concentrations in the environment. This may lead to
undesirable environmental effects and thus warrants risk assessment. The
ecotoxicity testing of a wide variety of ENMs rapidly evolving in the market is
costly but also ethically questionable when bioassays with vertebrates are
conducted. Therefore, alternative methods, e.g., models for predicting toxicity
mechanisms of ENMs based on their physico-chemical properties (e.g., quantitative
(nano)structure-activity relationships, QSARs/QNARs), should be developed. While
the development of such models relies on good-quality experimental toxicity data,
most of the available data in the literature even for the same test species are
highly variable. In order to map and analyse the state of the art of the existing
nanoecotoxicological information suitable for QNARs, we created a database NanoE
Tox that is available as Supporting Information File 1. The database is based on
existing literature on ecotoxicology of eight ENMs with different chemical
composition: carbon nanotubes (CNTs), fullerenes, silver (Ag), titanium dioxide
(TiO2), zinc oxide (ZnO), cerium dioxide (CeO2), copper oxide (CuO), and iron
oxide (FeO x ; Fe2O3, Fe3O4). Altogether, NanoE-Tox database consolidates data
from 224 articles and lists altogether 1,518 toxicity values (EC50/LC50/NOEC)
with corresponding test conditions and physico-chemical parameters of the ENMs as
well as reported toxicity mechanisms and uptake of ENMs in the organisms. 35% of
the data in NanoE-Tox concerns ecotoxicity of Ag NPs, followed by TiO2 (22%),
CeO2 (13%), and ZnO (10%). Most of the data originates from studies with
crustaceans (26%), bacteria (17%), fish (13%), and algae (11%). Based on the
median toxicity values of the most sensitive organism (data derived from three or
more articles) the toxicity order was as follows: Ag > ZnO > CuO > CeO2 > CNTs >
TiO2 > FeO x . We believe NanoE-Tox database contains valuable information for
ENM environmental hazard estimation and development of models for predicting
toxic potential of ENMs.
PMID- 26425435
TI - Optimized design of a nanostructured SPCE-based multipurpose biosensing platform
formed by ferrocene-tethered electrochemically-deposited cauliflower-shaped gold
nanoparticles.
AB - The demand for on-site nanodevices is constantly increasing. The technology
development for the design of such devices is highly regarded. In this work, we
report the design of a disposable platform that is structured with cauliflower
shaped gold nanoparticles (cfAuNPs) and we show its applications in immunosensing
and enzyme-based detection. The electrochemical reduction of Au(III) allows for
the electrodeposition of highly dispersed cauliflower-shaped gold nanoparticles
on the surface of screen-printed carbon electrodes (SPCEs). The nanostructures
were functionalized using ferrocenylmethyl lipoic acid ester which allowed for
the tethering of the ferrocene group to gold, which serves as an electrochemical
transducer/mediator. The bioconjugation of the surface with anti-human IgG
antibody (alpha-hIgG) or horseradish peroxidase (HRP) enzyme yields biosensors,
which have been applied for the selective electrochemical detection of human IgG
(hIgG) or H2O2 as model analytes, respectively. Parameters such as the number of
sweeps, amount of charge generated from the oxidation of the electrodeposited
gold, time of incubation and concentration of the ferrocene derivatives have been
studied using cyclic voltammetry (CV), electrochemical impedance spectroscopy
(EIS) and scanning electron microscopy (SEM). Selectivity and specificity tests
have been also performed in the presence of potentially interfering substances to
either hIgG or H2O2. Results showed that the devised immunosensor is endowed with
good selectivity and specificity in the presence of several folds of competitive
analytes. The enzyme-based platform showed a good catalytic activity towards H2O2
oxidation which predestined it to potential applications pertaining to enzymatic
kinetics studies. The levels of hIgG in human serum and H2O2 in honey were
successfully determined and served as assessment tools of the applicability of
the platforms for real samples analysis.
PMID- 26425436
TI - Large-voltage behavior of charge transport characteristics in nanosystems with
weak electron-vibration coupling.
AB - We study analytically the Full Counting Statistics of the charge transport
through a nanosystem consisting of a few electronic levels weakly coupled to a
discrete vibrational mode. In the limit of large transport voltage bias the
cumulant generating function can be evaluated explicitly based solely on the
intuitive physical arguments and classical master equation description of the
vibration mode. We find that for the undamped vibrational modes mutual dynamical
interplay between electronic and vibronic degrees of freedom leads to strongly
nonlinear (in voltage) transport characteristics of the nanosystem. In
particular, we find that for large voltages the k-th cumulant of the current
grows as V (2k) to be contrasted with the linear dependence in case of more
strongly externally damped and thus thermalized vibrational modes.
PMID- 26425437
TI - Nanocuration workflows: Establishing best practices for identifying, inputting,
and sharing data to inform decisions on nanomaterials.
AB - There is a critical opportunity in the field of nanoscience to compare and
integrate information across diverse fields of study through informatics (i.e.,
nanoinformatics). This paper is one in a series of articles on the data curation
process in nanoinformatics (nanocuration). Other articles in this series discuss
key aspects of nanocuration (temporal metadata, data completeness, database
integration), while the focus of this article is on the nanocuration workflow, or
the process of identifying, inputting, and reviewing nanomaterial data in a data
repository. In particular, the article discusses: 1) the rationale and importance
of a defined workflow in nanocuration, 2) the influence of organizational goals
or purpose on the workflow, 3) established workflow practices in other fields, 4)
current workflow practices in nanocuration, 5) key challenges for workflows in
emerging fields like nanomaterials, 6) examples to make these challenges more
tangible, and 7) recommendations to address the identified challenges. Throughout
the article, there is an emphasis on illustrating key concepts and current
practices in the field. Data on current practices in the field are from a group
of stakeholders active in nanocuration. In general, the development of workflows
for nanocuration is nascent, with few individuals formally trained in data
curation or utilizing available nanocuration resources (e.g., ISA-TAB-Nano).
Additional emphasis on the potential benefits of cultivating nanomaterial data
via nanocuration processes (e.g., capability to analyze data from across research
groups) and providing nanocuration resources (e.g., training) will likely prove
crucial for the wider application of nanocuration workflows in the scientific
community.
PMID- 26425438
TI - A novel link between FMR gene and the JNK pathway provides clues to possible role
in malignant pleural mesothelioma.
AB - Malignant pleural mesothelioma (MPM) is an aggressive form of thoracic cancer
with poor prognosis. While some studies have identified the molecular alterations
associated with MPM, little is known about their role in MPM. For example,
fragile X mental retardation (FMR) gene is up-regulated in MPM but its role in
MPM is unknown. Here, utilizing Drosophila genetics, I investigate the possible
role FMR may be playing in MPM. I provide evidence which suggests that FMR may
contribute to tumorigenesis by up-regulating a matrix metalloprotease (MMP) and
by degrading the basement membrane (BM), both important for tumor metastasis. I
also demonstrate a novel link between FMR and the JNK pathway and suggest that
the effects of FMR in MPM could in part be mediated by up-regulation of the JNK
pathway.
PMID- 26425440
TI - On the role of impulsivity and decision-making in suicidal behavior.
AB - Suicide risk constitutes a complex set of interacting demographic, clinical,
psychobiological and environmental variables. Impulsivity is a long-known risk
factor for suicide attempts. However, research based on clearer conceptual
refinement in this area is imperative. One emerging field of study is that of
decision-making. Impulsivity involves a failure of higher-order control,
including decision-making. Using standardized operational definitions that take
into consideration relevant aspects of impulsivity, including state- and trait
components and a deeper understanding of the process of decision-making in the
suicidal mind, we may come a step closer to understanding suicidality and winning
the fight in this scourge of human suffering.
PMID- 26425439
TI - Detection of circulating IgG antibodies to apolipoprotein B100 in acute
myocardial infarction.
AB - A number of studies have reported an association between increased levels of
antibodies against oxidized low-density lipoprotein (oxLDL) and cardiovascular
disease, but the anti-oxLDL antibody has not been confirmed to serve as an
effective biomarker for prediction of acute myocardial infarction (AMI).
Apolipoprotein B100 (ApoB100)-derived peptide fragments generated by proteolytic
degradation and aldehyde modification are the major antigens in oxLDL, and so the
present work was undertaken to detect circulating IgG for Apo-B100-derived
peptide antigens. An in-house enzyme-linked immunosorbent assay (ELISA) was
developed with eight ApoB100-derived peptide antigens (Ag1-Ag8) to detect
circulating anti-ApoB100 IgG levels in 267 patients with AMI and 201 control
subjects. Binary logistic regression analysis revealed that circulating IgG for
Ag1 was significantly higher in the patient group than the control group (P <
0.001) after adjustment for age, gender, smoking, hypertension, diabetes and
circulating levels of cholesterol, HDL, LDL, ApoA and ApoB100. None of the other
seven antigens detected an increase in IgG levels in AMI patients compared with
control subjects. Spearman correlation analysis showed no correlation between IgG
antibody for Ag1 and clinical characteristics. In conclusion, the linear peptide
antigens derived from ApoB100 may be suitable for the development of an ELISA
antibody test for prediction of AMI, although further confirmation is still
needed in large-scale clinical studies.
PMID- 26425441
TI - Role of presynaptic phosphoprotein synapsin II in schizophrenia.
AB - Synapsin II is a member of the neuronal phosphoprotein family. These
phosphoproteins are evolutionarily conserved across many organisms and are
important in a variety of synaptic functions, including synaptogenesis and the
regulation of neurotransmitter release. A number of genome-wide scans, meta
analyses, and genetic susceptibility studies have implicated the synapsin II gene
(3p25) in the etiology of schizophrenia (SZ) and other psychiatric disorders.
Further studies have found a reduction of synapsin II mRNA and protein in the
prefrontal cortex in post-mortem samples from schizophrenic patients. Disruptions
in the expression of this gene may cause synaptic dysfunction, which can result
in neurotransmitter imbalances, likely contributing to the pathogenesis of SZ. SZ
is a costly, debilitating psychiatric illness affecting approximately 1.1% of the
world's population, amounting to 51 million people today. The disorder is
characterized by positive (hallucinations, paranoia), negative (social
withdrawal, lack of motivation), and cognitive (memory impairments, attention
deficits) symptoms. This review provides a comprehensive summary of the
structure, function, and involvement of the synapsin family, specifically
synapsin II, in the pathophysiology of SZ and possible target for therapeutic
intervention/implications.
PMID- 26425444
TI - Months backward test: A review of its use in clinical studies.
AB - AIM: To review the use of the Months Backwards Test (MBT) in clinical and
research contexts. METHODS: We conducted a systematic review of reports relating
to the MBT based upon a search of PsychINFO and MEDLINE between January 1980 and
December 2014. Only reports that specifically described findings pertaining to
the MBT were included. Findings were considered in terms of rating procedures,
testing performance, psychometric properties, neuropsychological studies and use
in clinical populations. RESULTS: We identified 22 data reports. The MBT is
administered and rated in a variety of ways with very little consistency across
studies. It has been used to assess various cognitive functions including focused
and sustained attention as well as central processing speed. Performance can be
assessed in terms of the ability to accurately complete the test without errors
("MB accuracy"), and time taken to complete the test ("MB duration"). Completion
time in cognitively intact subjects is usually < 20 s with upper limits of 60-90
s typically applied in studies. The majority of cognitively intact adults can
complete the test without error such that any errors of omission are strongly
suggestive of cognitive dysfunction. Coverage of clinical populations, including
those with significant cognitive difficulties is high with the majority of
subjects able to engage with MBT procedures. Performance correlates highly with
other cognitive tests, especially of attention, including the digit span
backwards, trailmaking test B, serial threes and sevens, tests of simple and
complex choice reaction time, delayed story recall and standardized list learning
measures. Test-retest and inter-rater reliability are high (both > 0.90).
Functional magnetic resonance imaging studies comparing the months forward test
and MBT indicate greater involvement of more complex networks (bilateral middle
and inferior frontal gyri, the posterior parietal cortex and the left anterior
cingulate gyrus) for backwards cognitive processing. The MBT has been usefully
applied to the study of a variety of clinical presentations, for both cognitive
and functional assessment. In addition to the assessment of major
neuropsychiatric conditions such as delirium, dementia and Mild Cognitive
Impairment, the MBT has been used in the assessment of concussion, profiling of
neurocognitive impairments in organic brain disorders and Parkinson's disease,
prediction of delirium risk in surgical patients and medication compliance in
diabetes. The reported sensitivity for acute neurocognitive disturbance/delirium
in hospitalised patients is estimated at 83%-93%. Repeated testing can be used to
identify deteriorating cognitive function over time. CONCLUSION: The MBT is a
simple, versatile tool that is sensitive to significant cognitive impairment.
Performance can be assessed according to accuracy and speed of performance.
However, greater consistency in administration and rating is needed. We suggest
two approaches to assessing performance - a simple (pass/fail) method as well as
a ten point scale for rating test performance (467).
PMID- 26425443
TI - Usefulness of telepsychiatry: A critical evaluation of videoconferencing-based
approaches.
AB - Telepsychiatry, i.e., the use of information and communication technologies to
provide psychiatric services from a distance, has been around for more than half
a century now. Research over this period has shown that videoconferencing-based
telepsychiatry is an enabling and empowering form of service delivery, which
promotes equality of access, and high levels of satisfaction among patients. The
range of services offered by videoconferencing-based telepsychiatry, potential
users and points of delivery of such services are theoretically limitless.
Telepsychiatry has both clinical utility and non-clinical uses such as
administrative, learning and research applications. A large body of accumulated
evidence indicates that videoconferencing-based telepsychiatric assessments are
reliable, and clinical outcomes of telepsychiatric interventions are comparable
to conventional treatment among diverse patient populations, ages and diagnostic
groups, and on a wide range of measures. However, on many aspects of
effectiveness, the evidence base is still relatively limited and often
compromised by methodological problems. The lack of cost-effectiveness data in
particular, is a major hindrance, raising doubts about the continued viability of
telepsychiatric services. Added to this are the vagaries of technology, negative
views among clinicians, poor uptake by providers, and several legal, ethical and
administrative barriers. These hamper the widespread implementation of
telepsychiatry and its integration with routine care. Though further advances in
technology and research are expected to solve many of these problems, the way
forward would be to promote telepsychiatry as an adjunct to conventional care,
and to develop hybrid models, which incorporate both traditional and
telepsychiatric forms of mental health-care.
PMID- 26425442
TI - Psychiatric aspects of brain tumors: A review.
AB - Infrequently, psychiatric symptoms may be the only manifestation of brain tumors.
They may present with mood symptoms, psychosis, memory problems, personality
changes, anxiety, or anorexia. Symptoms may be misleading, complicating the
clinical picture. A comprehensive review of the literature was conducted
regarding reports of brain tumors and psychiatric symptoms from 1956-2014. Search
engines used include PubMed, Ovid, Psych Info, MEDLINE, and MedScape. Search
terms included psychiatric manifestations/symptoms, brain tumors/neoplasms. Our
literature search yielded case reports, case studies, and case series. There are
no double blind studies except for post-diagnosis/-surgery studies. Early
diagnosis is critical for improved quality of life. Symptoms that suggest work-up
with neuroimaging include: new-onset psychosis, mood/memory symptoms, occurrence
of new or atypical symptoms, personality changes, and anorexia without body
dysmorphic symptoms. This article reviews the existing literature regarding the
diagnosis and management of this clinically complex condition.
PMID- 26425445
TI - Motor abilities of children and adolescents with a psychiatric condition: A
systematic literature review.
AB - AIM: To summarize research regarding the motor abilities of children and
adolescents who suffer from a common psychiatric condition. METHODS: In order to
outline the current knowledge regarding the motor abilities of children and
adolescents with autism spectrum disorders (ASD), attention deficit hyperactivity
disorder (ADHD), disruptive behavior disorders (DBD) and depression, a
comprehensive systematic literature search was carried out using PubMed, Medline
and ERIC databases. The databases were searched for relevant English language
articles published between January 1990 and April 2014. Only studies that
conducted a quantitative evaluation of motor ability and concerned individuals
aged 0-18 years were included. A separate search was conducted for each disorder
(ASD, ADHD, DBD, depression) in conjunction with each of the following keywords:
(psycho/perceptuo) motor/movement skill(s), (psycho/perceptuo) motor/movement
abilities, (psycho/perceptuo) motor/movement impairment, (psycho/perceptuo)
motor/movement problem(s), motor function, motor coordination, motor performance,
motor deficit(s). To detect supplementary relevant literature, the reference
lists of the retrieved articles were examined. RESULTS: The search strategy
yielded 51 studies meeting the inclusion criteria. In total, 28 studies were
included that examined the motor abilities of children and adolescents with ASD.
All studies indicated that they performed below average on various standardized
motor assessment instruments. The overall prevalence rate for impairment in motor
abilities ranged from 33% to 100%. Twenty-seven studies examined the motor
abilities of children and adolescents with ADHD. Depending on the type of motor
assessment tool and the cut-off points used by different researchers, prevalence
rates of impairment in motor abilities are highly variable and ranged from 8% to
73%. Remarkably, there is a paucity of research addressing the motor abilities of
individuals with DBD or depression. Furthermore, methodological problems, such as
measurement and comorbidity issues, complicate the generalization of the
findings. CONCLUSION: Research suggests that motor impairment is highly prevalent
in some psychiatric conditions, particularly ASD and ADHD. However, future work
is necessary to draw sound conclusions.
PMID- 26425448
TI - Video-assisted surgery for thyroid cancer patients.
AB - BACKGROUND: Today is well known that endoscopic thyroidectomy could reach the
same level of completeness as a conventional operation. We have been using
minimally invasive video assisted thyroidectomy (MIVAT) as our favorite minimally
invasive access to thyroid diseases from the late nineties. METHODS: Our
experience with MIVAT is represented by 2,413 cases between 1998 and 2014: in
particular 821 patients were operated with a total thyroidectomy for a papillary
carcinoma (34.0%). Furthermore 967 patients underwent a MVAT for the presence of
an undetermined lesion (40.0%). RESULTS: The conversion rate was very low: 24
patients (1.0%), mainly due to: unexpected posterior tracheal invasions (nine
patients), involvement of lymph nodes not evident at echography (four patients),
esophageal infiltration (three patients), strap muscles infiltration (three
patients) and finally in five cases the presence of serious thyroiditis that had
escaped to ultrasonographic evaluation. CONCLUSIONS: The minimally MIVAT to treat
malignant thyroid tumors has today a very clear indication for malignancies.
PMID- 26425447
TI - Influence of gender in the recognition of basic facial expressions: A critical
literature review.
AB - AIM: To conduct a systematic literature review about the influence of gender on
the recognition of facial expressions of six basic emotions. METHODS: We made a
systematic search with the search terms (face OR facial) AND (processing OR
recognition OR perception) AND (emotional OR emotion) AND (gender or sex) in
PubMed, PsycINFO, LILACS, and SciELO electronic databases for articles assessing
outcomes related to response accuracy and latency and emotional intensity. The
articles selection was performed according to parameters set by COCHRANE. The
reference lists of the articles found through the database search were checked
for additional references of interest. RESULTS: In respect to accuracy, women
tend to perform better than men when all emotions are considered as a set.
Regarding specific emotions, there seems to be no gender-related differences in
the recognition of happiness, whereas results are quite heterogeneous in respect
to the remaining emotions, especially sadness, anger, and disgust. Fewer articles
dealt with the parameters of response latency and emotional intensity, which
hinders the generalization of their findings, especially in the face of their
methodological differences. CONCLUSION: The analysis of the studies conducted to
date do not allow for definite conclusions concerning the role of the observer's
gender in the recognition of facial emotion, mostly because of the absence of
standardized methods of investigation.
PMID- 26425446
TI - Pharmacologic approaches to treatment resistant depression: Evidences and
personal experience.
AB - AIM: To review evidence supporting pharmacological treatments for treatment
resistant depression (TRD) and to discuss them according to personal clinical
experience. METHODS: Original studies, clinical trials, systematic reviews, and
meta-analyses addressing pharmacological treatment for TRD in adult patients
published from 1990 to 2013 were identified by data base queries (PubMed, Google
Scholar e Quertle Searches) using terms: "treatment resistant depression",
"treatment refractory depression", "partial response depression", "non responder
depression", "optimization strategy", "switching strategy", "combination
strategy", "augmentation strategy", selective serotonin reuptake inhibitors
antidepressants (SSRI), tricyclic antidepressants (TCA), serotonin norepinephrine
reuptake inhibitors antidepressants, mirtazapine, mianserine, bupropione,
monoamine oxidase inhibitor antidepressant (MAOI), lithium, thyroid hormones,
second generation antipsychotics (SGA), dopamine agonists, lamotrigine,
psychostimulants, dextromethorphan, dextrorphan, ketamine, omega-3 fatty acids, S
adenosil-L-metionine, methylfolat, pindolol, sex steroids, glucocorticoid agents.
Other citations of interest were further identified from references reported in
the accessed articles. Selected publications were grouped by treatment strategy:
(1) switching from an ineffective antidepressant (AD) to a new AD from a similar
or different class; (2) combining the current AD regimen with a second AD from a
different class; and (3) augmenting the current AD regimen with a second agent
not thought to be an antidepressant itself. RESULTS: Switching from a TCA to
another TCA provides only a modest advantage (response rate 9%-27%), while
switching from a SSRI to another SSRI is more advantageous (response rate up to
75%). Evidence supports the usefulness of switching from SSRI to venlafaxine (5
positive trials out 6), TCA (2 positive trials out 3), and MAOI (2 positive
trials out 2) but not from SSRI to bupropione, duloxetine and mirtazapine. Three
reviews demonstrated that the benefits of intra- and cross-class switch do not
significantly differ. Data on combination strategy are controversial regarding
TCA-SSRI combination (positive results in old studies, negative in more recent
study) and bupropion-SSRI combination (three open series studies but not three
controlled trails support the useful of this combination) and positive regard
mirtazapine (or its analogue mianserine) combination with ADs of different
classes. As regards the augmentation strategy, available evidences supported the
efficacy of TCA augmentation with lithium salts and thyroid hormone (T3), but are
conflicting regard the SSRI augmentation with these two drugs (1 positive trial
out of 4 for lithium and 3 out of 5 for thyroid hormone). Double-blind controlled
studies showed the efficacy of AD augmentation with aripiprazole (5 positive
trials out 5), quetiapine (3 positive trials out 3) and, at less extent, of
fluoxetine augmentation with olanzapine (3 positive trials out 6), so these drugs
received the FDA indication for the acute treatment of TRD. Results on AD
augmentation with risperidone are conflicting (2 short term positive trials, 1
short-term and 1 long-term negative trials). Case series and open-label trials
showed that AD augmentation with pramipexole or ropinirole, two dopamine
agonists, could be an effective treatment for TRD (response rate to pramipexole
48%-74%, to ropinirole 40%-44%) although one recent double-blind placebo
controlled study does not support the superiority of pramipexole over placebo.
Evidences do not justify the use of psychostimulants, omega-3 fatty acids, S
adenosil-L-metionine, methylfolate, pindolol, lamotrigine, and sex hormone as AD
augmentation for TRD. Combining the available evidences with our experience we
suggest treating non-responders to one SSRI bupropion or mirtazapine trial by
switching to venlafaxine, and non-responders to one venlafaxine trial by
switching to a TCA or, if TCA are not tolerated, combining mirtazapine with SSRI
or venlafaxine. In non-responders to two or more ADs (including at least one TCA
if tolerated) current AD regimen could be augmented with lithium salts (mainly in
patients with bipolar depression or suicidality), SGAs (mostly aripiprazole) or
DA-agonists (mostly pramipexole). In patients with severe TRD, i.e., non
responders to combination and augmentation strategies as well as to
electroconvulsive therapy if workable, we suggest to try a combination plus
augmentation strategy. CONCLUSION: Our study identifies alternative effective
treatment strategies for TRD. Further studies are needed to compare the efficacy
of different strategies in more homogeneous subpopulations.
PMID- 26425449
TI - Electrophysiological neural monitoring of the laryngeal nerves in thyroid
surgery: review of the current literature.
AB - Recurrent laryngeal nerve (RLN) injury is one of the most common complications of
thyroid surgery. RLN injury can cause vocal cord paralysis, affecting the
patient's voice and the quality of life. Injury of the external branch of the
superior laryngeal nerve (EBSLN) can cause cricothyroid muscle denervation
affecting high vocal tones. Thus, securing the laryngeal nerves in these
surgeries is of utmost importance. Visual identification of the nerves has long
been the standard method for this precaution. Intraoperative neuromonitoring
(IONM) has been introduced as a novel technology to improve the protection of the
laryngeal nerves and reduce the rate of RLN injury. The aim of this article is to
provide a brief description of the technique and review the literature to
illustrate the value of IONM. IONM can provide early identification of anatomical
variations and unusual nerve routes, which carry a higher risk of injury if not
detected. IONM helps in prognosticating postoperative nerve function. Moreover,
by detecting nerve injury intraoperatively, it aids in staging bilateral
surgeries to avoid bilateral vocal cord paralysis and tracheostomy. The article
will discuss the value of continuous IONM (C-IOMN) that may prevent nerve injury
by detecting EMG waveform changes indicating impending nerve injury. Herein, we
are also discussing anatomy of laryngeal nerves and aspects of its injury.
PMID- 26425450
TI - Remote access thyroid surgery.
AB - Robot assisted thyroid surgery has been the latest advance in the evolution of
thyroid surgery after endoscopy assisted procedures. The advantage of a superior
field vision and technical advancements of robotic technology have permitted
novel remote access (trans-axillary and retro-auricular) surgical approaches.
Interestingly, several remote access surgical ports using robot surgical system
and endoscopic technique have been customized to avoid the social stigma of a
visible scar. Current literature has displayed their various advantages in terms
of post-operative outcomes; however, the associated financial burden and also
additional training and expertise necessary hinder its widespread adoption into
endocrine surgery practices. These approaches offer excellent cosmesis, with a
shorter learning curve and reduce discomfort to surgeons operating ergonomically
through a robotic console. This review aims to provide details of various remote
access techniques that are being offered for thyroid resection. Though these have
been reported to be safe and feasible approaches for thyroid surgery, further
evaluation for their efficacy still remains.
PMID- 26425451
TI - Transaxillary single-incision robotic neck dissection for metastatic thyroid
cancer.
AB - In head and neck area, neck dissection (ND) is one of the most complex and
precision-needed procedure. The long cervical scar and post-operative neck
discomfort have been also inevitable brands after this procedure. Heretofore, few
dare to try endoscopic surgical technique to the ND mainly due to its complexity
and jeopardy of complication. Although, there have been several reports about the
endoscopic approaches for functional ND or ND, they had so many technical and
instrumental limitations. The dexterities of the surgical robotics have advanced
the techniques of endoscopic surgery, and have facilitated the most precise and
delicate endoscopic surgical procedure in head and neck area. The technical
feasibility and early surgical outcomes of robotic ND using the transaxillary
approach for the management of metastatic thyroid cancer have already been
reported as satisfactory. Robotic ND can allow complete compartment-oriented
lymph node (LN) dissection without any fatal complications, or compromising
oncologic principles. We previously described a novel method of robotic
thyroidectomy with ND using a gasless transaxillary approach for metastatic
thyroid cancer, and here, we firstly introduce a less invasive robotic procedure
which has been modified from the original one, which we refer to as the
transaxillary single-incision robotic ND.
PMID- 26425452
TI - Robotic transaxillary thyroid surgery.
AB - Recent technological advances have led to a rapid progress in endocrine surgery.
With the advent of minimally invasive techniques in thyroid surgery, robot
assisted transaxillary thyroid surgery (RATS) has emerged as one of the most
promising approaches. Its main advantages are improved cosmetic outcome, avoiding
cervical incisions, increased patient satisfaction, improved visualization, arms
articulations, eliminating surgeon's natural tremor, thereby increasing
precision. The main disadvantages are longer operative time, and increased cost
compared to conventional thyroidectomy, as well as potential injuries to the
brachial plexus, skin flap, esophagus, and trachea. Large-scale studies, mainly
from South-Korea, have proved that in skilled hands, RATS is a safe alternative
to conservative thyroidectomy and should be presented to patients with aesthetic
concerns. As with any new emerging technique, careful patient selection is
crucial, and further evidence must be sought to confirm its indications.
PMID- 26425453
TI - Robotic facelift thyroid surgery.
AB - Techniques for thyroid surgery have advanced dramatically over the past two
decades, driven by a better understanding of thyroid physiology, anatomy, and
perioperative management strategies. Improvements in surgical technology have
permitted surgeons to perform minimally invasive surgery associated with less
dissection, decreased pain, smaller anterior cervical incisions, and most
importantly a faster recovery. The advent of robotic surgical technology has
allowed the development of remote access thyroidectomy for select patients who
wish to avoid a visible cervical incision completely. The robotic facelift
thyroidectomy (RFT) approach also offers the advantage of outpatient surgery
without the need for postoperative drainage. A growing body of evidence supports
the safety and efficacy of the approach, and as a result the technique is now
being performed at several centers around the world.
PMID- 26425454
TI - Minimally invasive parathyroid surgery.
AB - Traditionally, bilateral cervical exploration for localization of all four
parathyroid glands and removal of any that are grossly enlarged has been the
standard surgical treatment for primary hyperparathyroidism (PHPT). With the
advances in preoperative localization studies and greater public demand for less
invasive procedures, novel targeted, minimally invasive techniques to the
parathyroid glands have been described and practiced over the past 2 decades.
Minimally invasive parathyroidectomy (MIP) can be done either through the
standard Kocher incision, a smaller midline incision, with video assistance
(purely endoscopic and video-assisted techniques), or through an ectopically
placed, extracervical, incision. In current practice, once PHPT is diagnosed,
preoperative evaluation using high-resolution radiographic imaging to localize
the offending parathyroid gland is essential if MIP is to be considered. The
imaging study results suggest where the surgeon should begin the focused
procedure and serve as a road map to allow tailoring of an efficient, imaging
guided dissection while eliminating the unnecessary dissection of multiple glands
or a bilateral exploration. Intraoperative parathyroid hormone (IOPTH) levels may
be measured during the procedure, or a gamma probe used during radioguided
parathyroidectomy, to ascertain that the correct gland has been excised and that
no other hyperfunctional tissue is present. MIP has many advantages over the
traditional bilateral, four-gland exploration. MIP can be performed using local
anesthesia, requires less operative time, results in fewer complications, and
offers an improved cosmetic result and greater patient satisfaction. Additional
advantages of MIP are earlier hospital discharge and decreased overall associated
costs. This article aims to address the considerations for accomplishing MIP,
including the role of preoperative imaging studies, intraoperative adjuncts, and
surgical techniques.
PMID- 26425455
TI - Robotic transaxillary and retroauricular parathyroid surgery.
AB - Current advancement in robotic surgery has provided a safe, precise, 3
dimensional (3D) magnified dissection for parathyroid surgery without the need
for CO2 insufflation, and with a better cosmetic outcome due to an invisible scar
in the axillary or retroauricular region. Preoperative imaging studies that
assist in the localization of lesions have been key elements in patients'
selection for targeted parathyroid surgery.
PMID- 26425456
TI - Transoral robotic thyroid surgery.
AB - There is currently significant demand for minimally invasive thyroid surgery;
however the majority of proposed surgical approaches necessitate a compromise
between minimal tissue dissection with a visible cervical scar or extensive
tissue dissection with a remote, hidden scar. The development of transoral
endoscopic thyroid surgery however provides an approach which is truly minimally
invasive, as it conceals the incision within the oral cavity without
significantly increasing the amount of required dissection. The transoral
endoscopic approach however presents multiple technical challenges, which could
be overcome with the incorporation of a robotic operating system. This manuscript
summarizes the literature on the feasibility and current clinical experience with
transoral robotic thyroid surgery.
PMID- 26425457
TI - Laparoscopic and robotic adrenal surgery: transperitoneal approach.
AB - Recent advances in technology and the need to decrease surgical morbidity have
led a rapid progress in laparoscopic adrenalectomy (LA) over the past decade.
Robotics is attractive to the surgeon owing to the 3-dimensional image quality,
articulating instruments, and stable surgical platform. The safety and efficacy
of robotic adrenalectomy (RA) have been demonstrated by several reports. In
addition, RA has been shown to provide similar outcomes compared to LA.
Development of adrenal surgery has involved the description of several surgical
approaches including the anterior transperitoneal, lateral transperitoneal (LT)
and posterior retroperitoneal (PR). Among these, the most frequently preferred
technique is LT adrenalectomy, primarily due to the surgeon's familiarity of the
operative field, wider working space and visibility. The LT technique is suitable
for the resection of larger, unilateral tumors and in scenarios where conversion
to an open transperitoneal approach is warranted, it offers a lesser burden.
Also, the larger view of the entire abdominal cavity and excellent exposure of
both adrenal glands and surrounding structures provided by the LT technique
render it safe and feasible in pediatric and pregnant individuals.
PMID- 26425458
TI - Surgical approaches for liver metastases in carcinoid tumors.
AB - Liver is the commonest site for metastasis in patients with neuroendocrine tumors
(NETs); it occurs in 45-95% of patients. Available treatment options include
surgical resection, liver transplantation, chemotherapy and biotherapy. Surgery
is the gold standard for curative therapy. Typically, a multidisciplinary
approach is a cornerstone for decision making while dealing with this aggressive
disease. This review will focus on the performance and safety of open,
laparoscopic, and liver transplant surgical approaches in NETs patients with
liver metastases.
PMID- 26425459
TI - Robotic-assisted laparoscopic adrenalectomy for an adrenal adenoma.
AB - The patient was referred for management of a left adrenal incidentaloma.
Preoperative CT scan and MRI showed focal calcification. Here we are presenting
this video demonstrating robotic-assisted laparoscopic adrenalectomy for left
adrenal mass.
PMID- 26425460
TI - Role of bilateral adrenalectomy in adrenocorticotropic hormone-dependent
Cushing's syndrome.
PMID- 26425461
TI - Only generics (drugs/names): Is India ready?
PMID- 26425462
TI - Statins: Cholesterol guidelines and Indian perspective.
AB - Statins have become an important drug in preventing the occurrence of
atherosclerotic cardiovascular disease (ASCVD). The effectiveness of statins in
reducing ASCVD has been established in large-scale clinical trials. The lipid
management guidelines have been periodically modified due to accumulating
evidence about the proportionate benefit achieved with a progressive reduction in
cholesterol levels with higher doses of statins and even in those at low risk of
development of ASCVD. The current American College of Cardiology/American Heart
Association guidelines have based its recommendations from data gathered
exclusively from randomized controlled trials. It has simplified the use of
statins, but also raised questions regarding the validity of its cardiovascular
event risk prediction tool. Epidemiology of cardiovascular disease in India
differs from the western population; there is an increased the prevalence of
metabolic syndrome and atherogenic dyslipidemia phenotype a group not addressed
in the current guidelines. The guidelines are based on trials, which do not have
a representative South Asian population. This article reviews the relevant
literature, and examines the issues involved in adopting the guidelines to the
Indian population.
PMID- 26425463
TI - Pleiotropic effects of statins.
AB - Statins or 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors not
only prevents the synthesis of cholesterol biosynthesis but also inhibits the
synthesis of essential isoprenoid intermediates such as farnesyl pyrophosphate,
geranylgeranyl pyrophosphate, isopentanyl adenosine, dolichols and polyisoprenoid
side chains of ubiquinone, heme A, and nuclear lamins. These isoprenoid
intermediates are required for activation of various intracellular/signaling
proteins- small guanosine triphosphate bound protein Ras and Ras-like proteins
like Rho, Rab, Rac, Ral, or Rap which plays an indispensible role in multiple
cellular processes. Reduction of circulating isoprenoids intermediates as a
result of HMG CoA reductase inhibition by statins prevents activation of these
signalling proteins. Hence, the multiple effects of statins such as
antiinflammatory effects, antioxidant effects, antiproliferative and
immunomodulatory effects, plaque stability, normalization of sympathetic outflow,
and prevention of platelet aggregation are due to reduction of circulating
isoprenoids and hence inactivation of signalling proteins. These multiple lipid
independent effects of statins termed as statin pleiotropy would potentially open
floodgates for research in multiple treatment domains catching attentions of
researchers and clinician across the globe.
PMID- 26425464
TI - Bariatric surgery and diabetes remission: Who would have thought it?
AB - Type 2 diabetes mellitus (T2DM) and obesity are increasingly common and major
global health problems. The Edmonton obesity staging system clearly pointed
towards increased mortality proportionate to the severity of obesity. Obesity
itself triggers insulin resistance and thereby poses the risk of T2DM. Both
obesity and T2DM have been associated with higher morbidity and mortality and
this calls for institution of effective therapies to deal with the rising trend
of complications arising out of this dual menace. Although lifestyle changes form
the cornerstone of therapy for both the ailments, sustained results from this
modalities is far from satisfactory. While Look AHEAD (action for HEAalth in
diabetes) study showed significant weight loss, reduction in glycated hemoglobin
and higher remission rate of T2DM at 1(st) year following intensive lifestyle
measures; recurrence and relapse rate bounced back in half of subjects at 4
years, thereby indicating that weight loss and glycemic control is difficult to
maintain in the long term with lifestyle interventions. Same recurrence
phenomenon was also observed with pharmacotherapy with rimonabant, sibutramine
and orlistat. Bariatric surgery has been seen to associate with substantial and
sustained weight loss in morbidly obese patients. Interestingly, bariatric
surgeries also induce higher rates of short and long-term diabetes remission.
Although the exact mechanism behinds this diabetes remission are not well
understood; improved insulin action, beta-cell function and complex interplay of
hormones in the entero-insular axis appears to play a major role. This article
reviews the effectiveness of bariatric procedures on remission or improvement in
diabetes and put a perspective on its implicated mechanisms.
PMID- 26425466
TI - Profile of liver enzymes in non-alcoholic fatty liver disease in patients with
impaired glucose tolerance and newly detected untreated type 2 diabetes.
AB - CONTEXT: The perception of non-alcoholic fatty liver disease (NAFLD) as an
uncommon and benign condition is rapidly changing. Approximately, 70% type 2
diabetes mellitus (T2DM) patients have a fatty liver, which may follow an
aggressive course with necroinflammation and fibrosis. AIMS: To assess the
profile of liver enzymes in subjects with impaired glucose tolerance (IGT), new
onset treatment naive T2DM and normal glucose tolerance (NGT) with and without
NAFLD. SETTINGS AND DESIGN: Cross-sectional clinic-based study. SUBJECTS AND
METHODS: 152 IGT and 158 recently detected T2DM subjects aged between 30 and 69
years, along with 160 age and gender matched controls with NGT. An
ultrasonography scan of the upper abdomen was done in all patients in order to
examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were
also analyzed in all patients. STATISTICAL ANALYSIS USED: Unpaired t-test, Chi
square/Fisher Exact test (for categorical variables), Pearson/Spearmen
correlation test to find significant difference, association and correlation
between two or more groups respectively. RESULTS: NAFLD was significantly
associated with higher alanine aminotransferase (ALT) and gamma-glutamyl
transferase (GGT) but not ALP levels in IGT and T2DM patients. ALT, GGT
significant correlated with waist circumference, body mass index, fasting
insulin, homeostatic model assessment- insulin resistance, fasting blood glucose,
high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had
normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15
and 30 U/L. ALT <25 U/L and GGT <15 U/L had highest negative predictivity whereas
ALT >40 U/L and GGT > 30 U/L had highest positive predictivity for presence of
NAFLD in our study sample. CONCLUSIONS: Mild elevations of liver enzymes in the
upper normal range are associated with features of metabolic syndrome and NAFLD
even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes
are warranted in order to prevent unnecessary diagnostic work-ups and early
detection of NAFLD to reduce the risk of cirrhosis, hepatocellular carcinoma and
classical cardiovascular disease in T2DM and IGT patients.
PMID- 26425467
TI - Iodine nutritional status in Himachal Pradesh state, India.
AB - INTRODUCTION: Iodine deficiency (ID) is the preventable causes of mental
retardation worldwide. Himachal Pradesh (HP) state is a known endemic region to
ID. OBJECTIVE: the objective was to assess the current status of iodine nutrition
in a population of HP, India. METHODOLOGY: There are three regions in HP namely:
Kangra, Mandi, and Shimla. In each region, one district was selected namely:
Kangra, Kullu, and Solan. In each district, 30 clusters were identified by
utilizing population proportional-to-size cluster sampling methodology. A total
of 5748 school-age children (SAC) (Kangra; 1864, Kullu; 1986, Solan: 1898), 1711
pregnant mothers (PMs) (Kangra; 647, Kullu; 551, Solan: 513), and 1934 neonates
(Kangra; 613, Kullu; 638, Solan: 683), were included in study. Clinical
examination of thyroid of each child and PM was conducted. Casual urine samples
were collected from children and PMs. Cord blood samples were collected for
estimation of thyroid stimulating hormone (TSH) among neonates. RESULTS: In SAC,
total goiter rate (TGR) was 15.8% (Kangra), 23.4% (Kullu), and 15.4% (Solan).
Median urinary iodine concentration (UIC) level was 200 MUg/l (Kangra), 175 MUg/l
(Kullu), and 62.5 MUg/l (Solan). In PMs, TGR was 42.2% (Kangra), 42.0% (Kullu),
and 19.9% (Solan). Median UIC level was 200 MUg/l (Kangra), 149 MUg/l (Kullu),
and 130 MUg/l (Solan). In Neonates, TSH levels of > 5 mIU/L were found in 73.4
(Kangra), 79.8 (Kullu), and 63.2 (Solan) percent of neonates. CONCLUSION: As per,
UIC level (<100 MUg/l) in SAC, ID was found in district Solan. In Kullu and Solan
districts, there were ID (UIC level < 150 MUg/l) among PMs. TSH levels indicated
ID in all districts surveyed.
PMID- 26425465
TI - Place of sulfonylureas in the management of type 2 diabetes mellitus in South
Asia: A consensus statement.
AB - Since their introduction in clinical practice in the 1950's, Sulfonylureas (SUs)
have remained the main-stay of pharmacotherapy in the management of type 2
diabetes. Despite their well-established benefits, their place in therapy is
inappropriately being overshadowed by newer therapies. Many of the clinical
issues associated with the use of SUs are agent-specific, and do not pertain to
the class as such. Modern SUs (glimepiride, gliclazide MR) are backed by a large
body of evidence, experience, and most importantly, outcome data, which supports
their role in managing patients with diabetes. Person-centred care, i.e., careful
choice of SU, appropriate dosage, timing of administration, and adequate patient
counseling, will ensure that deserving patients are not deprived of the
advantages of this well-established class of anti-diabetic agents. Considering
their efficacy, safety, pleiotropic benefits, and low cost of therapy, SUs should
be considered as recommended therapy for the treatment of diabetes in South Asia.
This initiative by SAFES aims to encourage rational, safe and smart prescription
of SUs, and includes appropriate medication counseling.
PMID- 26425469
TI - Vitamin D status and gestational diabetes mellitus.
AB - CONTEXT: Vitamin D (Vit D) deficiency and gestational diabetes mellitus (GDM) are
increasingly being seen in Indian women. The role of Vit D in causing GDM is not
clear. AIMS: (1) To compare Vit D status in pregnant women with or without GDM.
(2) Frequency of GDM in women with Vit D insufficiency and deficiency. (3) To
reassess glucose tolerance after replacement of Vit D in those women with Vit D
deficiency and GDM. SETTINGS AND DESIGN: Tertiary Care Hospital, Antenatal Care
Department based prospective, controlled study. SUBJECTS AND METHODS: Seventy
eight consecutive women (<28 weeks gestational period) were screened for GDM by
glucose tolerance test (GTT) (75 g 2 h). Fifty-nine of these women were confirmed
to have GDM (2 h postglucose > 140 mg/dl). Eight of these women were excluded as
per laid exclusion criteria. Remaining 19 women with normal glucose tolerance
(NGT) were included as controls. Serum 25-OH Vit D level was estimated by
radioimmuno assay. Standard advice regarding diet, sunlight exposure, and
exercise was given to all by the same dietician. Women with Vit D levels below 20
ng/ml were prescribed 60,000 IU of oral cholecalciferol to be administered twice
weekly for 4 weeks. GTT was repeated after 6 weeks. Frequency of glucose
intolerance was compared between Vit D sufficient and deficient groups. Women
with GDM and Vit D deficiency who revert to NGT after supplementation with
cholecalciferol were evaluated. STATISTICAL ANALYSIS USED: Paired t-test for
comparing means, and Fisher's test for comparing proportions. RESULTS: Baseline
characteristics of GDM and NGT with respect to their age, prepregnancy body mass
index, and gestational period were comparable. Serum 25-OH Vit D levels were
significantly lower in GDM 24.7 (+/-17.6) ng/ml versus NGT (45.8 +/- 28) group (P
= 0.0004). Frequency of GDM was similar irrespective of Vit D status 67% versus
42% (P = 0.09). Standard advice on diet and exercise with or without Vit D
supplementation did not significantly differ in the conversion of GDM to NGT (P =
0.63). CONCLUSION: Although Vit D deficiency is associated with GDM however its
replacement does not reverse the glucose intolerance. There is no justification
at present for routine screening for Vit D deficiency or its replacement in the
management of GDM.
PMID- 26425468
TI - Bone mineral content has stronger association with lean mass than fat mass among
Indian urban adolescents.
AB - INTRODUCTION: There are conflicting reports on the relationship of lean mass (LM)
and fat mass (FM) with bone mineral content (BMC). Given the high prevalence of
Vitamin D deficiency in India, we planned the study to evaluate the relationship
between LM and FM with BMC in Indian children and adolescents. The objective of
the study was to evaluate the relationship of BMC with LM and FM. MATERIALS AND
METHODS: Total and regional BMC, LM, and FM using dual energy X-ray
absorptiometry and pubertal staging were assessed in 1403 children and
adolescents (boys [B]: 826; girls [G]: 577). BMC index, BMC/LM and BMC/FM ratio,
were calculated. RESULTS: The age ranged from 5 to 18 years, with a mean age of
13.2 +/- 2.7 years. BMC adjusted for height (BMC index and BMC/height ratio) was
comparable in both genders. There was no difference in total BMC between genders
in the prepubertal group but were higher in more advanced stages of pubertal
maturation. The correlation of total as well as regional BMC was stronger for LM
(B: Total BMC - 0.880, trunk - 0.715, leg - 0.894, arm - 0.891; G: Total BMC -
0.827, leg - 0.846, arm - 0.815 (all value indicate r (2), P < 0.0001 for all)
when compared with FM (B: Total BMC - 0.776, trunk - 0.676, leg - 0.772, arm -
0.728; G: Total BMC - 0.781, leg - 0.741, arm - 0.689; all P < 0.0001) except at
trunk BMC (LM - 0.682 vs. FM - 0.721; all P < 0.0001), even after controlling for
age, height, pubertal stage, and biochemical parameters. CONCLUSIONS: BMC had a
stronger positive correlation with LM than FM.
PMID- 26425470
TI - Thyroid autoimmunity in pregnant Nigerians.
AB - CONTEXT: Thyroid autoimmunity is a recognized disorder in pregnancy and is
associated with a number of adverse pregnancy outcomes. AIM: This study set out
to determine the relationship between pregnancy and thyroid autoimmunity in
Nigerian women. SETTINGS AND DESIGN: This was an analytical cross-sectional study
carried out in a tertiary hospital in South Western Nigeria with a total study
population of 108 pregnant and 52 nonpregnant women. SUBJECTS AND METHODS: Serum
thyroid stimulating hormone, free thyroxine and thyroid peroxidase antibodies
(TPO-Ab) were quantitatively determined using enzyme linked immuno-assays.
Pregnant women were grouped into three categories (<14 weeks, 14-28 weeks and >
28 weeks). The relationship between pregnancy and thyroid autoimmunity was
determined using Spearman correlation. Analysis of variance was used in
comparison of means, Chi-square test used in analyzing proportions while P <=
0.05 was considered as significant. RESULTS: The mean age of the pregnant women
was 30.4 +/- 6.0 years while the mean gestational age of all pregnant women was
20.6 +/- 9.6 weeks. The mean TPO-Ab of 11.58 IU/ml in the pregnant was
significantly higher than that of the controls of 7.23 IU/ml (P < 0.001). Out of
108 pregnant women, 27 (25%) had elevated TPO-Ab as against about 2% of the
nonpregnant women levels P < 0.001. The number of pregnant women with elevated
TPO-Ab levels decreased from 33.3% in the first group to 25.6% and 15.2% in the
second and third groups. CONCLUSION: Thyroid autoimmunity expressed by the
presence of TPO-Ab is high among pregnant Nigerian women and the frequency of
autoimmunity appears to decline with advancing gestational age.
PMID- 26425471
TI - Posology of insulins: A review of standard textbooks and product inserts.
AB - OBJECTIVES: The study is aimed to assess whether the information contained in
standard pharmacology, endocrinology, and diabetology textbooks regarding timings
of administration, frequency and dose of various insulins is adequate and also to
see whether the information contained in these texts is concordant with product
inserts. MATERIALS AND METHODS: Four standard textbooks of pharmacology, two of
diabetology and three of endocrinology were assessed for the published
information regarding dose, timing, and frequency of insulin administration. The
product inserts of commonly available insulins in India were also studied for the
same. RESULTS: Various omissions and disparities could be seen in the coverage of
insulins in standard textbooks. Posology information about premixed insulins and
basal insulins have been omitted by the majority of the textbooks. Details about
dose, frequency and timings of ultra-short acting insulins have also not been
covered by all textbooks. Some discrepancies regarding prescribing information
was also noted in product inserts, especially in case of newer insulins.
CONCLUSIONS: Thus, this article stresses upon the need of a uniform source of
information for providing adequate and standardized knowledge regarding timing,
frequency, and dose of insulins.
PMID- 26425472
TI - Appropriateness of using prevalent national standards for assessment of growth
parameters in children from Uttarakhand.
AB - BACKGROUND: With distinct geographical and demographic conditions prevalent in
the regions of Himalayan foothills, it seems questionable to assess the children
from these areas using the standards based upon growth pattern of children from
major central cities of the country. To answer this question, we compared the
growth parameters of apparently healthy children, attending our out-patient
clinic, with corresponding median values for age from national reference data.
MATERIALS AND METHODS: The growth parameters of apparently healthy children were
compared with the expected value for age that is, median value for the
corresponding age from the recommended national reference data (Agarwal et al).
RESULTS: Data from 205 boys and 200 girls, aged 5-18 years, were finally
evaluated. The considerable difference was observed between growth parameters.
Children from Uttarakhand were observed to be lighter, especially in older age
groups and taller, especially in younger age groups, when compared with
corresponding median values from reference data. CONCLUSION: It appears
inappropriate to interpret the growth parameters of the children of this region
in the background of index national reference.
PMID- 26425473
TI - Plasma free metanephrine, normetanephrine, and 3-methoxytyramine for the
diagnosis of pheochromocytoma/paraganglioma.
AB - BACKGROUND: Pheochromocytomas (PHEO) and paragangliomas (PGL) are derived from
paraganglia of the sympathetic and parasympathetic nervous system. Most of the
sympathetic PHEO/PGL secrete either catecholamine or their metabolites,
metanephrines, whereas parasympathetic PHEO/PGL are nonsecretory. We assessed the
utility of plasma free 3-methoxytyramine (3MT), normetanephrine (NM), and
metanephrine (MN) for the diagnosis of PHEO/PGL. MATERIALS AND METHODS: Sixty
five patients referred to endocrine/ENT clinics were enrolled. Twelve patients
with von Hippel-Lindau (VHL), neurofibromatosis type 1 (NF1) and multiple
endocrine neoplasia type 2 (MEN2) syndromes were excluded. Remaining 53 patients
(39 patients with adrenal, abdominal, cervical and thoracic PHEO/PGL and 14
patients with head and neck PGL (HNPGL) were taken for this study. Sixty-five age
and sex-matched subjects were taken as controls. Plasma levels 3MT, NM, and MN
were measured using high-performance liquid chromatography. Receivers operating
characteristics was plotted and cut-off levels were established. RESULTS: When
compared with controls, there was a 36-, 8.7- and 9.5-fold increase in levels of
NM, 3MT and MN in the patients with PHEO/PGL and 7.2- and 2.7-fold increase in
3MT and NM, in the patients with HNPGL, respectively. In malignant PHEO/PGL,
there was a 99-, 16- and 20-fold increase and in benign PHEO/PGL, there was 19-,
6.8- and 6.4-fold increase in levels of NM, 3MT, and MN, respectively. NM in
combination with MN was high in 97% of the patients with PHEO/PGL. All three
metabolites in combination were high in 83% of patients with HNPGL. In malignant
PHEO/PGL, 50% subjects had increased levels of both NM and 3MT. CONCLUSIONS:
Measurement of plasma-free NM along with 3MT and MN provides a better tool for
the diagnosis of PHEO/PGL as well as HNPGL. Further, NM in combination with 3MT
can be used for the diagnosis of malignant PHEO/PGL.
PMID- 26425474
TI - Pioglitazone and the risk of bladder cancer: An Indian retrospective cohort
study.
AB - AIM: To determine whether pioglitazone is associated with an increased risk of
bladder cancer among Indian type 2 diabetic patients. METHODS: A retrospective
data analysis of 2222 type 2 diabetic patients was conducted. The study subjects
were divided into two equal groups: 1111 pioglitazone users and 1111 pioglitazone
non-users. The safety of pioglitazone therapy was analyzed in terms of occurrence
of bladder and other types of cancers along with its efficacy in terms of
glycemic control. Parameters for assessing safety were duration of disease,
duration of usage and total dose of pioglitazone consumed across age groups,
glycemic control, obesity and family history of any cancer. Bladder cancer
prevalence was analyzed on the basis of urinary cytology, urine routine and
microscopy, hematuria, urinary nuclear matrix protein 22 analysis and
ultrasonography. RESULTS: Of the 2222 cases analysed, there was no evidence of
bladder cancer in any of the studied groups, (p=not significant) which was also
evident among 1111 patients on Pioglitazone therapy with a cumulative dose
consumption of 2737 mg to 1,31,400 mg. On subgroup analysis, there was no
evidence of bladder cancer amongst patients with age >60 years, duration of
diabetes > 10 years and uncontrolled diabetics (HbA1c >8%) with cumulative
pioglitazone consumption of >28,000 mg. A significant number of patients achieved
good glycemic control (HbA1c <7.5%) with pioglitazone therapy. CONCLUSION:
Pioglitazone therapy was not associated with occurrence of bladder cancer among
Indian type 2 diabetic patients and demonstrated good glycemic control.
PMID- 26425475
TI - Clinical profile and inheritance pattern of CYP21A2 gene mutations in patients
with classical congenital adrenal hyperplasia from 10 families.
AB - CONTEXT: Congenital adrenal hyperplasia (CAH) is an autosomal recessive metabolic
disorder caused by mutations in the CYP21A2 gene. Genetic diagnosis of 21-OH
deficiency causing CAH is more complicated than any other monogenic disorder due
to high variability of the locus. The disease has a wide spectrum of clinical
variants making it difficult to establish a genotyp-phenotype correlation.
Therefore, family studies are necessary to ascertain parental genotype and
segregation of the mutant allele among the offspring. AIM: The present study
aimed to identify CYP21A2 gene mutations and analyze the segregation pattern in
CAH trios (patients and their parents). MATERIALS AND METHODS: A total of ten
families having at least one CAH child were recruited. RESULTS: Out of 31
children from ten families, 15 were affected with CAH and 13 of/them (12 females
and 1 male) were available for genetic testing. One family had all the children
affected with CAH. Compound heterozygous mutations were identified in seven
patients (53.8%) whereas p.P30L, In2 and Delta8 bp mutations were present in
homozygous state in three (23.1%), two (15.3 %) and one (7.6%) patient
respectively. CONCLUSIONS: In majority of the families, mutant alleles observed
in the patients were inherited from the parents whereas three families showed
sporadic mutations without any paternal or maternal origin. This indicated their
novel occurrence due to misalignment of the parental genes and/or large deletion
of the gene. Female preponderance was noted in the CAH families and also among
the patients raising the possibility of survival advantage among females.
PMID- 26425476
TI - Prevalence of obesity and central obesity among adolescent girls in a district
school in Bangladesh.
AB - INTRODUCTION: The prevalence of childhood obesity has increased over the last two
decades. Obesity is a major risk factor for chronic diseases and plays a central
role in insulin resistance or metabolic syndrome. METHODS: The aim of the study
was to assess the prevalence of obesity and abdominal obesity by means of body
mass index (BMI) and waist-to-height ratio (WHtR) in adolescent girls in a
district school in Bangladesh. Based on age and sex specific BMI percentiles, the
students were classified as normal weight (5(th)-<85(th) percentile), overweight
(85(th)-<95(th) percentiles), and obese (>=95(th) percentile). Central obesity
was categorized as WHtR >= 0.5. Adolescent girls (aged 9-17 years) attending the
sixth to twelfth grades (n = 501) in a Bengali medium school participated in the
study. RESULTS: The prevalence of obesity and overweight were 23% and 14% among
the girls. The prevalence of central obesity was 26%. Around 14% of girls in the
normal weight group were centrally obese. There was a significant relationship
between WHtR and BMI status (P = 0.0001). CONCLUSION: Our study provides evidence
showing a high prevalence of overall and central obesity in adolescent girls in
our population. We emphasize the need for further large scale surveillance
programs and preventive strategies in our population to reduce the incidence of
obesity.
PMID- 26425477
TI - Effect of integrated approach of yoga therapy on autonomic functions in patients
with type 2 diabetes.
AB - BACKGROUND AND OBJECTIVES: Integrated approach of yoga therapy (IAYT) had shown
beneficial effects in the management of type 2 diabetes mellitus (DM). Autonomic
dysfunction is one of the major complications of type 2 DM. Research studies have
demonstrated that yoga can modulate autonomic functions. Hence, the current study
was designed to assess the effect of IAYT on autonomic functions in type 2
diabetics. MATERIALS AND METHODS: 15 patients of type 2 DM with ages ranging from
35 to 60 years were recruited for the study. They were diagnosed with type 2
diabetes from 1-year to 15 years. Assessments were made on day 1 (before yoga)
and day 7 (after 1-week of yoga practice). Heart rate variability (HRV), blood
pressure (BP) response to the isometric handgrip and heart rate response to deep
breathing were assessed before and after 1-week of IAYT. RESULTS: There was a
significant reduction in fasting plasma glucose from 154.67-130.27 mg/dL
(Wilcoxon signed rank test, P = 0.029) following 1-week of IAYT. BP response to
isometric hand grip improved significantly (Wilcoxon signed rank test, P = 0.01).
There was no statistical significant change in HRV components and heart rate
response to deep breathing test. However, there was a trend of increase in the
low frequency power (41.07%), high frequency power (6.29%), total power (5.38%),
and standard deviation of all NN intervals (SDNN) (6.29%). CONCLUSION: These
findings suggest that, IAYT improved autonomic functions in type 2 diabetes
patients.
PMID- 26425478
TI - Insulin aspart in patients with gestational diabetes mellitus and pregestational
diabetes mellitus.
AB - AIMS: This study was undertaken to assess the effectiveness and safety of insulin
aspart in patients with gestational and pregestational diabetes. SETTINGS AND
DESIGN: An open-label, prospective, nonrandomized, comparative, and observational
study conducted at single center in India. SUBJECTS AND METHODS: A total of 276
patients were in gestational diabetes mellitus (GDM) group, 79 were in the pre
GDM group. Patients were started on insulin therapy (insulin aspart +/- neutral
protamine hagedorn) once medical nutrition therapy for 2 weeks failed to achieve
control, that is., fasting plasma glucose >=90 mg/dL and/or 1.0 h postprandial
plasma glucose >=130 mg/dL. Insulin dose was titrated to keep the blood glucose
values between 90 and 130 mg/dL. Patients were followed once every 4 weeks until
the 28(th) week, then once every 2 weeks until 32(nd) week, then once every week
until delivery, and the final visit was on 60 +/- 7 days. The final outcome was
assessed in terms of incidence of macrosomia (>3.5 kg body weight) between the
two groups and episodes of confirmed (blood glucose <56 mg/dL) minor or major
maternal hypoglycemia. RESULTS: There was no statistically significant difference
among the two groups in terms of incidence of macrosomia that is., it was 5.1%,
8.9% in GDM, pre-GDM group, respectively. CONCLUSIONS: Insulin aspart was found
safe in pregnancy, however, more studies with double-blind, standard controlled
studies are required to confirm the findings of this study.
PMID- 26425479
TI - Metabolic syndrome among Jaffna Tamil community, Sri Lanka.
AB - AIM: The prevalence and associated risk factors of metabolic syndrome (MS) among
adults over 18 years old in Jaffna district. MATERIALS AND METHODS: It was
community-based cross-sectional descriptive study. Multistage stratified cluster
sampling technique was employed. An interviewer administered questionnaire was
used to obtain the relevant information. Waist circumference (WC) and blood
pressure (BP) measurements were recorded. Fasting plasma glucose (FPG), high
density lipoprotein (HDL), and triacylglycerols were analyzed by the enzymatic
colorimetric assay using semi-automated analyzer (Teco Diagnostics TC-3300).
International Diabetic Federation guideline for Asians was used to identify MS.
RESULTS: Sample response rate was 95.3% and of them, 43.8% (n = 224) was male.
The prevalence of central obesity (WC for male >=90 cm, female >=80 cm) was
23.9%. Raised FPG (>=100 mg/dL, or previously diagnosed diabetes mellitus),
hypertriacylglycerolemia (>=150 mg/dl), low level of HDL cholesterol (<40 mg/dL
in males, <50 mg/dL in females), and raised BP (systolic BP >=130 or diastolic BP
>=85 mmHg or previously diagnosed hypertension) were found in 23.9%, 25%, 79.3%,
and 36.6% of the participants. The prevalence of MS was 15.8% (95% confidence
interval [CI]: 12.8-19.3) and it was 17.4% in males and 14.6% in females.
Participants living in the urban area had a higher prevalence of MS when compared
with participants in a rural area (P = 0.015). Older age (P < 0.001) was a risk
factor for development of MS. Smoking (P = 0.005) was a risk factor for the
development of MS. Participants having sedentary, moderately active, and highly
active lifestyle had the prevalence of MS 20.6% (95% CI: 13.2-29.7), 14.7% (95%
CI: 10.6-19.5), and 14.7% (95% CI: 9.3-21.6), respectively (P = 0.247).
CONCLUSION: Older age, urban living, and smoking carry a higher risk for
development of MS among Jaffna Tamil community.
PMID- 26425480
TI - Association of low educational status with microvascular complications in type 2
diabetes: Jaipur diabetes registry-1.
AB - OBJECTIVE: To determine the association of educational status (ES), as a marker
of socioeconomic status, with the prevalence of microvascular complications in
diabetes. METHODS: Successive patients (n = 1214) presenting to our centre were
evaluated for sociodemographic, anthropometric, clinical, and therapeutic
variables. Subjects were classified according to ES into Group 1 (illiterate,
216); Group 2 (=25 kg/m(2) 64.0%, abdominal obesity 63.4%, hypertension 67.5%, high fat
diet 14.5%, low fruits/vegetables 31.8%, low fibre intake 60.0%, high salt diet
16.9%, physical inactivity 27.5%, coronary, or cerebrovascular disease 3.0%, and
microvascular disease (peripheral, ocular or renal) in 20.7%. Microvascular
disease was significantly greater in illiterate (25.9%) and low (23.6%) compared
to middle (15.0%) and high (14.7%) ES groups (P < 0.05). Age- and sex-adjusted
logistic regression analysis revealed that in illiterate and low ES groups
respectively, prevalence of smoking/tobacco use (odds ratio 3.84, confidence
intervals 2.09-7.05 and 2.15, 1.36-3.41); low fruit/vegetable (2.51, 1.53-4.14
and 1.99, 1.30-3.04) and low fibre intake (4.02, 2.50-6.45 and 1.78, 1.23-2.59)
was greater compared to high ES. Poor diabetes control (HbA1c >8.0%) was
significantly greater in illiterate (38.0%), low (46.0%) and middle (41.0%)
compared to high (31.5%) ES subjects (P < 0.05). CONCLUSIONS: There is a greater
prevalence of the microvascular disease in illiterate and low ES diabetes
patients in India. This is associated with the higher prevalence of
smoking/tobacco use, poor quality diet and sub-optimal diabetes control.
PMID- 26425481
TI - Clinical profile of diabetic ketoacidosis in tertiary care hospital of Eastern
Nepal.
AB - INTRODUCTION: Diabetes ketoacidoisis (DKA) is characterized by hyperketonaemia,
metabolic acidosis, and hyperglycemia. AIMS: The aim of this study was to
describe the demographic profile, clinical characterstics of patients admitted
with diabetic ketoacidosis in BPKIHS, medical ward. SETTINGS AND DESIGN: The
hospital based descriptive study. MATERIALS AND METHODS: We took all the patients
admitted with a diagnosis of diabetic ketoacidosis (DKA) as defined ADA 2006
consensus statement in medical ward from January 2010 to December 2010. The
statistical operations was done through Manufactured by IBM Corp. RESULTS: Only
sixteen patients (7 type 1 and 9 type 2DM) were with DKA. When compared to the 16
subjects with type 1 DM, the type 2 were older (56.8 s 25.7 years) and had a
significantly higher PH levels (7.11 s 7.28 P = 0.04). The mean body mass index
was 20.5+/-2.44 in both Type 1 and type 2 DM. Four were on diet control and
Insulin respectively. Five were on oral hypoglycemic agents (OHA) and three on
both (insulin and OHA). Infection was most common precipitating factor (56.25%)
followed by poor drug compliance (37.5%) and first presentation (6.25%).
CONCLUSIONS: We found majority of patients were type 2 DM. Metabolic acidosis has
significant association in both type of diabetic. We found infection was the most
common precipitating factor for DKA.
PMID- 26425482
TI - The making of an endocrinologist in India: Life and times at Institute of Post
Graduate Medical Education and Research Calcutta.
AB - Endocrinology is relatively one of the newer super-specialties of internal
medicine. Following higher secondary schooling, it takes anywhere between 13 and
18 years to become a super-specialist in India, which holds true for
endocrinology also. This article intends to highlight the life and the journey of
making an endocrinologist in India, through personal experiences, focusing on
Institute of Post Graduate Medical Education and Research (IPGMER) Calcutta, the
largest super-specialty teaching hospital and research institute of Eastern
India. In general, there is lack of adequate exposure to endocrinology during the
Bachelor of Medicine, Bachelor of Surgery and MD Internal Medicine Training in
India. Pre-Doctorate of Medicine (DM) senior residency goes a long way in
developing an orientation for endocrinology. Endocrinology DM entrance
examinations are usually a rigorous intimidating affair. Endocrinology training
at IPGMER was a heady mix of managing huge number of patients with diverse
endocrinopathies, laboratory work, academic presentations, and clinical research.
The support and back up provided by the entire faculty enhanced the learning
process. As I look back, the 3 years of DM residency flew by like the wink of the
eye. The journey of endocrinology is the journey of a lifetime.
PMID- 26425483
TI - Fasts, feasts, and festivals in diabetes: Glycemic management during Parsi
rituals.
AB - The article is one in the series of articles related to glycaemic management in
festivals across all religions in India. The article discusses issues in
glycaemic management among Parsi culture, which represent a small but ever
important group of Indian population.
PMID- 26425484
TI - Hemoglobin E disease and glycosylated hemoglobin.
AB - Glycosylated hemoglobin (HbA1C) is a routinely measured parameter to monitor long
term glycemic control in people with diabetes mellitus. The presence of
hemoglobin (Hb) variants can affect the accuracy of HbA1C methods. Hb E variant
is the most common Hb variant in South-east Asia and North-east India. In the
presence of Hb E, HbA1C may not be detectable by ion-exchange chromatography
(high-pressure liquid chromatography), but may be estimated by immunoassay
technique and boronate affinity chromatography. However, the result may be
underestimated when correlated with plasma glucose and serum fructosamine levels.
Clinicians should be aware of this limitation of HbA1C estimation in patients
with Hb E and other Hb variants.
PMID- 26425485
TI - High-mix insulins.
AB - Premix insulins are commonly used insulin preparations, which are available in
varying ratios of different molecules. These drugs contain one short- or rapid
acting, and one intermediate- or long-acting insulin. High-mix insulins are
mixtures of insulins that contain 50% or more than 50% of short-acting insulin.
This review describes the clinical pharmacology of high-mix insulins, including
data from randomized controlled trials. It suggests various ways, in which high
mix insulin can be used, including once daily, twice daily, thrice daily, hetero
mix, and reverse regimes. The authors provide a rational framework to help
diabetes care professionals, identify indications for pragmatic high-mix use.
PMID- 26425486
TI - The resolution of anemia after curative parathyroidectomy is sustained even after
a decade.
PMID- 26425487
TI - Endocrine Society of India Fun Research Workshop 2015: The participants
perspective.
PMID- 26425488
TI - Endocrinology training in India: A student's perspective.
PMID- 26425489
TI - Mid-Ventricular Variant of Dobutamine-Induced Stress Cardiomyopathy.
AB - INTRODUCTION: Dobutamine stress testing is a commonly used modality in detecting
and estimating the prognosis in coronary artery disease (CAD). Although it is
well tolerated by most patients, adverse events have been reported. Rarely,
transient wall motion abnormalities can occur in the absence of obstructive CAD
to suggest stress cardiomyopathy. CASE PRESENTATION: We report a 48-year-old
female with intermittent chest pain. Her physical exam, cardiac enzymes and
transthoracic echocardiogram were unremarkable. She underwent dobutamine stress
echocardiogram to rule out obstructive CAD. After 40 micrograms (mcg)/kg/minute
and 0.5 mg atropine, she complained of intense chest pain and became
hypertensive. Stress echocardiogram demonstrated mid-anterior and mid-septal
hypokinesis. Emergent coronary angiogram demonstrated normal coronaries. Left
ventricular angiogram in the right anterior oblique projection revealed mid
ventricular ballooning during systole with apical and basal hypercontractility.
Patient demonstrated excellent recovery with expectant management. CONCLUSIONS:
The mechanism of mid-variant of Dobutamine-induced stress cardiomyopathy remains
unclear. We think that multiple mechanisms are involved and this risk should be
considered in patients with comorbid psychiatric conditions and with use of
centrally acting stimulants.
PMID- 26425490
TI - Community Priority Index: Utility, Applicability and Validation for Priority
Setting in Community-Based Participatory Research.
AB - BACKGROUND: Providing practitioners with an intuitive measure for priority
setting that can be combined with diverse data collection methods is a necessary
step to foster accountability of the decision-making process in community
settings. Yet, there is a lack of easy-to-use, but methodologically robust
measures, that can be feasibly implemented for reliable decision-making in
community settings. To address this important gap in community based
participatory research (CBPR), the purpose of this study was to demonstrate the
utility, applicability, and validation of a community priority index in a
community-based participatory research setting. DESIGN AND METHODS: Mixed-method
study that combined focus groups findings, nominal group technique with six key
informants, and the generation of a Community Priority Index (CPI) that
integrated community importance, changeability, and target populations.
Bootstrapping and simulation were performed for validation. RESULTS: For pregnant
mothers, the top three highly important and highly changeable priorities were:
stress (CPI=0.85; 95%CI: 0.70, 1.00), lack of affection (CPI=0.87; 95%CI: 0.69,
1.00), and nutritional issues (CPI=0.78; 95%CI: 0.48, 1.00). For non-pregnant
women, top priorities were: low health literacy (CPI=0.87; 95%CI: 0.69, 1.00),
low educational attainment (CPI=0.78; 95%CI: 0.48, 1.00), and lack of self-esteem
(CPI=0.72; 95%CI: 0.44, 1.00). For children and adolescents, the top three
priorities were: obesity (CPI=0.88; 95%CI: 0.69, 1.00), low self-esteem
(CPI=0.81; 95%CI: 0.69, 0.94), and negative attitudes toward education (CPI=0.75;
95%CI: 0.50, 0.94). CONCLUSIONS: This study demonstrates the applicability of the
CPI as a simple and intuitive measure for priority setting in CBPR. Significance
for public healthCommunity-based participatory research (CBPR) has been credited
to be a promising approach for the reduction of health disparities and as an
effective way to create sustainable community outcomes. Priority setting is an
essential decision-making step in community-based participatory research. Issue
prioritization must be driven not just by the importance of the issue, but also
what realistically can be changed with available funds. However, there is little
guidance on how to approach priority setting with objective and subjective
measures while implementing CBPR. This study depicts the invention of a Community
Priority Index (CPI), which can be used to prioritize community health issues by
combining subjective and objective markers into a single measure. The CPI shown
in this study represents a viable systematic approach to improve the objectivity
and reliability of community-based decision-making.
PMID- 26425492
TI - Knowledge and Behavioural Factors Associated with Gender Gap in Acquiring HIV
Among Youth in Uganda.
AB - BACKGROUND: The increasing prevalence of HIV in Uganda during the last decade
(7.5% in 2004-05 to 8.3% in 2011 among women and 5.0% in 2004-05 to 6.1% among
men in 2011 of 15 to 49 years) clearly shows that women are disproportionately
affected by HIV epidemic. Hence, we assessed the prevalence of HIV and focused on
differences in risky sexual behaviour and knowledge of HIV among Ugandan youth.
DESIGN AND METHODS: Uganda AIDS Indicator Survey 2011 data was used. The total
samples of men and women (15 to 24 years), interviewed and tested for HIV, were
3450 and 4504 respectively. The analysis of risky sexual behaviour was based on
1941 men and 3127 women who had ever had sex and were tested for HIV. Pearson's
Chi-square test and multivariate logistic regression analysis were used. RESULTS:
Findings showed that young women were almost two times more vulnerable than young
men in acquiring HIV (OR=1.762, P<0.001). Women who had first sex under age 15
(7.3%), had more than 2 sexual partners (9.2%) and did not use condom during last
sex (6.4%) were more HIV-positive. Higher risk was found among women (6.3%) than
men (2.2%). Significantly (P<0.01) less percentage (81.3%) of women as compared
to men (83.8%) perceived that the probability of HIV transmission may be reduced
by correct and consistent use of the condom during sex. CONCLUSIONS: Hence, there
is an urgent need for effective strategies and programmes to raise awareness on
sexual health and risky behaviour, particularly targeting the youth, which will
reduce the gender gap in risky sexual behaviour and new transmission of HIV in
Uganda. Significance for public healthThe present study represents the evidence
of a recent increase in HIV infection in Uganda from the latest round of AIDs
indicator survey. This manuscript describes how young women (15-24 years-old) are
disproportionately HIV-infected compared to young men in Uganda. They are more
vulnerable to HIV than young men. Moreover, it is also observed that young women
are at greater risk of acquiring HIV because of their risky sexual behaviour and
inappropriate knowledge of HIV transmission. Some educational programmes, growing
gender equity in HIV/AIDS activities and services, dropping violence and
coercion, addressing male norms and behaviours, improving women's legal
protection, and rising women's access to income and productive resources can be
very effective in minimising the vulnerability of young women to HIV/AIDS.
PMID- 26425491
TI - Diabetic Peripheral Neuropathy and its Determinants among Patients Attending a
Tertiary Health Care Centre in Mangalore, India.
AB - BACKGROUND: The burden of diabetes mellitus (DM) is on the rise especially in
developing countries like India. Due to its chronic nature DM tends to cause many
debilitating complications and diabetic peripheral neuropathy (DPN) is one of
them. The aim of this study is to determine the prevalence of DPN among patients
attending a tertiary care hospital and to identify the determinants associated
with it. DESIGN AND METHODS: A cross sectional study was conducted in Government
Wenlock Hospital, Mangalore (India), during January-February 2014. A total of 208
patients with >5 year duration of DM were asked to respond to the patient history
version of Michigan Neuropathy Screening Instrument (MNSI) and examinations were
conducted after obtaining consent from them. The statistical analysis was done in
terms of descriptive statistics and association between variables was tested
using logistic regression test. RESULTS: The prevalence of DPN using the MNSI
history version and MNSI examination were found to be 18.3% and 32.2%
respectively. The major determinants associated with DPN were found to be male
gender (OR: 2.7, CI: 1.4-5.1, P=0.001), smoking (OR: 5.8, CI: 1.9-17.3, P=0.001)
and age >40 years (OR: 2.7, CI: 1.2-5.8, P=0.011). CONCLUSIONS: The burden of
undetected DPN was found to be higher among diabetics, with an especially higher
prevalence among males, smokers and those with long standing diabetes mellitus.
Interventions in the form of early detection through routine screening, smoking
cessation and regular follow up examinations would go a long way in reducing the
burden of disability among diabetics and improve their quality of life
significantly. Significance for public healthThe findings of the current research
hold importance since diabetes is one of the leading causes of morbidity and
mortality across the world. Due to its chronic nature and effects of
hyperglycaemia, diabetes tends to be associated with many comorbidities, like
peripheral neuropathy, nephropathy, retinopathy etc. The presence of diabetic
peripheral neuropathy leads to a reduced quality of life among diabetic patients
due to the trauma and consequent gangrenes andamputation. The concept of
secondary prevention can be applied to the prevention of diabetic peripheral
neuropathy using easy to apply screening tools and thus help in early diagnosis
and treatment to reduce the burden of this debilitating illness.
PMID- 26425493
TI - Investigation on the Trace Elemental Profile of Sewage Workers in Kolkata, an
Indian Megacity.
AB - BACKGROUND: Environmental pollution has become a global health risk. Exposure to
pollutants at the work place, i.e. occupational exposure, is one of the areas
that need immediate attention. The civic drainage workers are exposed to
pollutants present in the wastewater they handle and most of them are toxic heavy
metals. Exposure to such pollutants may be a health hazard, since it can lead to
the imbalance in nutrient elements status. DESIGN AND METHODS: In the present
study, profiling of trace elements in the blood of drainage worker population
from an Indian megacity, Kolkata, was carried out by energy dispersive x-ray
fluorescence (EDXRF) and compared with the control group population of the same
area. RESULTS: The elements detected by EDXRF spectrometry include P, S, Cl, K,
Fe, Cu, Zn, Se, Br, and Rb. By using ANOVA with 5% significance level, we
observed significant alterations in the trace elements status, iron over loading,
selenium deficiency, and in Cu-Zn ratio. Gender specific variations within the
same population were also observed. CONCLUSIONS: The results indicate that the
drainage workers have altered elemental profile in comparison to that of control
population. Significance for public healthEnvironmental pollution is a global
health risk and awareness among sewage workers is growing very slowly in many
developing countries. Due to this fact, workers are often exposed to different
pollutants which are responsible for several health complications. Imbalances in
the presence of trace elements in blood are a symptom of different health status
and could also indicate new health perspectives for the future. In the present
scenario, this paper is essential since this kind of analysis has not been done
yet, especially regarding the health status of sewage workers. We hope this
initial study will be a starting point for future investigations.
PMID- 26425494
TI - Predicting Malawian Women's Intention to Adhere to Antiretroviral Therapy.
AB - BACKGROUND: With the increase in scaling up of antiretroviral therapy (ART),
knowledge of the need for adherence to ART is pivotal for successful treatment
outcomes. DESIGN AND METHODS: A cross-sectional study was carried out between
October and December 2013. We administered theory of planned behaviour (TPB) and
adherence questionnaires to 358 women aged 18-49 years, from a rural and urban
ART-clinics in southern Malawi. Hierarchical linear regression models were used
to predict intentions to adhere to ART. RESULTS: Regression models show that
attitude (beta=0.47), subjective norm (beta=0.31) and perceived behavioural
control (beta=0.12) explain 55% of the variance in intentions to adhere to ART.
The relationship between both food insecurity and perceived side effects with
intentions to adhere to ART is mediated by attitude, subjective norm, and
perceived behavioural control. Household (r=0.20) and individual (r=0.21) food
insecurity were positively and significantly correlated with perceived
behavioural control. Household food insecurity had a negative correlation with
perceived side effects (r=-0.11). Perceived side effects were positively
correlated with attitude (r=0.25). There was no statistically significant
relationship between intentions to adhere to ART in the future and one month self
report of past month adherence. These interactions suggest that attitude
predicted adherence only when food insecurity is high or perception of side
effects is strong. CONCLUSIONS: This study shows that modification might be
needed when using TPB constructs in resource constraint environments.
Significance for public healthThe knowledge of the rates of adherence to
antiretroviral therapy (ART) could be used to evaluate planning and project,
which could lead to better outcomes predicted by treatment efficacy data. In
addition, knowledge of adherence behaviour could help the development of
interventions focusing on collaboration between healthcare providers and Malawian
government to provide food support for patients on ART. The interventions could
also focus on providing better counselling support to improve beliefs regarding
control over taking the medication and perceived versus real side effects. It is
relevant for public health professors to understand factors influencing women's
ART adherence, in order to create interventions that are appropriate for
increasing ART adherence, which may lead to improved outcomes among women with
HIV living in endemic regions with limited treatment access.
PMID- 26425495
TI - Physician Gender and Lifestyle Counselling to Prevent Cardiovascular Disease: A
Nationwide Representative Study.
AB - BACKGROUND: Primary care physicians (PCPs) have a key role in the prevention of
cardiovascular diseases (CVD). However, it is not clear whether lifestyle
counselling behaviour differs between female and male PCPs. Nonetheless, this
information might be helpful to develop need-based advanced training for female
and male PCPs. Therefore, our aim was to identify potential gender differences in
the implementation of health promotion and the prevention of CVD in primary care.
DESIGN AND METHODS: In a Germany-wide survey called the ASP-kardio Study, we
collected data from 4074 PCPs (40% female; from October 2011 to March 2012). We
compared the provision of prevention measures, the attitude towards counselling,
and the potential barriers in counselling among female and male German PCPs. We
used chi(2) tests, Mann-Whitney U tests, and logistic regression analysis.
RESULTS: We found differences in all of the above-mentioned aspects. Female PCPs
were less likely to perceive barriers than male and more likely to ask patients
about lifestyle, for example, nutrition (OR=1.62, P<=0.001). Additionally, female
PCPs were more likely to feel well prepared (84.2% vs. 76.0%, P<=0.001) and
successful (75.6% vs. 68.0%, P<=0.001). Male PCPs were more likely to mention
barriers in daily practice that hinder lifestyle counselling. CONCLUSIONS:
Overall, both female and male PCPs had a positive attitude towards lifestyle
counselling. Nevertheless, in view of the barriers that they indicated,
incentives such as better reimbursement may help output-oriented PCPs to
translate their positive attitude into action. Moreover, awareness of gender
differences may help PCPs to acquire the specific advanced training that they
need for effective lifestyle counselling in CVD. Significance for public
healthLifestyle counselling is an important instrument to reduce the burden of
cardiovascular disease. Here, primary care physicians (PCPs) play an important
role as health advisors. Our study was able to identify deficits in the health
promotion behaviour of PCPs. Because of the gender differences revealed in our
study, male PCPs in particular should be sensitized to the importance and the
potentials of prevention and health promotion. Overcoming the barriers of
prevention and health promotion identified by the PCPs may be an important
starting point. If, for instance, PCPs were better financially compensated for
offering lifestyle counselling, which was rated as the most important barrier, it
is conceivable that more PCPs would start to incorporate such measures into their
daily routine. Additionally, a stronger focus on prevention and health promotion
during advanced training programs for PCPs could increase the use of lifestyle
counselling.
PMID- 26425496
TI - From Disappointment to Holistic Ideals: A Qualitative Study on Motives and
Experiences of Using Complementary and Alternative Medicine in Sweden.
AB - BACKGROUND: Recent studies indicate increased use of complementary and
alternative medicine (CAM) in western societies, to ameliorate health problems.
Even if there is substantial research on general patterns of use, there is
limited knowledge on individual motives. This study contributes to a qualitative
understanding of experiences of choosing and using CAM. DESIGN AND METHODS: This
study consists of in-depth interviews with 10 CAM users in Sweden. The
participants represent different backgrounds and experiences of using CAM. The
interviews have been analysed in accordance with content analysis. RESULTS: In
analysing experiences of choosing and using CAM four main themes were identified:
frustration and critique, values and ideology, individual responsibility, and
combining treatments. In general, the participants were highly reflexive on
issues concerning their health. They highlighted their own role and
responsibility, combined a variety of treatments, and continuously dealt with
questions on risks, even if they had relatively different approaches to if and
when to use CAM. The results also show that motives may change over time. Even if
initial choices were closely related to frustration and critique of conventional
treatments (for example, by perceiving conventional health care as limited, not
receiving proper diagnoses, or being critical to conventional drugs) was long
term use motivated by ideological characteristics of CAM (such as holistic and
individualized treatments, and extensive interaction with practitioners).
CONCLUSIONS: Four main themes, concerning experiences of choosing and using CAM
were identified. This study also supports the idea that initial motives for
choosing CAM may differ from those explaining long-term use. Significance for
public healthRecent studies indicate increased use of complementary and
alternative medicine (CAM), both in general western populations and specific
patient groups. Well-documented motives for choosing CAM are related to
disappointment and failure of conventional health care. In addition, there are
findings that demonstrate that certain basic values (such as individualism and
holistic orientations) are related to the use of CAM. A better understanding of
individual motives behind people's choice of CAM, and how this is related to
their perception of the health care system, is important for policy makers and
health care professionals alike. This study contributes to a qualitative
understanding of experiences of choosing and using CAM and how motives may change
over time. It also contributes with knowledge on how users combine CAM with
conventional health care and deal with risks.
PMID- 26425497
TI - The Relationship of Built Environment to Health-Related Behaviors and Health
Outcomes in Elderly Community Residents in a Middle Income Country.
AB - BACKGROUND: Few studies have examined the impact of the built environment (BE) on
health behaviours and health outcomes in middle income countries. This study
examines associations between self-assessed characteristics of the home and
neighbourhood environment and health-related behaviours and health outcomes in an
elderly population in Brazil. DESIGN AND METHODS: In a community sample of 6963
community dwellers 60 years old and older living in the state of Rio Grande do
Sul, Brazil, associations between self-reported BE conditions and health
behaviours and health outcomes were assessed using a structured questionnaire.
Multivariate analysis was conducted to investigate these associations while
accounting for other relevant characteristics. RESULTS: We found significant
positive associations between adverse BE conditions and pulmonary, urinary
conditions, gastrointestinal, problems, headache and depression. There were mixed
associations between adverse BE conditions and musculoskeletal and sensory
conditions, inverse associations with metabolic disorders. and no associations
with dermatologic problems and cancer. After accounting for health related
behaviours, results suggest a modest association between adverse BE conditions
and hypertension, with no significant associations with other indicators of
cardiovascular conditions (heart problems, stroke, varicose veins). CONCLUSIONS:
The findings in this study suggest links between adverse conditions in the BE and
health related behaviours in the hypothesized direction. Associations with the
health conditions examined here are mixed. We find the strongest evidence for
effects of adverse BE conditions for pulmonary and infectious conditions.
Significant associations between the adverse BE indicators and health outcomes
persist after accounting for health related behaviours, suggesting that BE
conditions are linked to health pathways above and beyond the health related
behaviours assessed in this study. Significance for public healthThe health
outcomes for which we found most consistent evidence of associations with the
built environment index (BEI) included respiratory conditions (bronchitis,
pneumonia), urinary and renal conditions, gastrointestinal problems, headache,
visual impairment and stroke. These health outcomes in the elderly may reflect
exposures in the household environment associated with inadequate housing, such
as mold, dust and damp. They may also be influenced by poor sanitary conditions,
reflected in the absence of indoor plumbing and inadequate waste disposal
facilities. Poor vision, headache and depression may all be associated with
chronic exposure to poverty and stress, for which the measures of the household
and neighborhood environmental conditions used in the BEI may be indicators.
Assuring that the elderly in Brazil have access to adequate housing located in
neighborhoods with access to basic sanitary conditions, water and lighting, will
be increasingly important as the average age of Brazilians continues to increase,
and increasing proportions of the population experience the adverse health
effects associated with these conditions.
PMID- 26425498
TI - A Stakeholder-Based System Dynamics Model of Return-to-Work: A Research Protocol.
AB - BACKGROUND: Returning to work following a job-related injury or illness can be a
complex process, influenced by a range of interrelated personal, psychosocial,
and organizational components. System dynamics modelling (SDM) takes a
sociotechnical systems perspective to view return-to-work (RTW) as a system made
up of multiple feedback relationships between influential components. DESIGN AND
METHODS: To build the RTW SDM, a mixed-method approach will be used. The first
stage, that has already been completed, involved creating a baseline model using
key informant interviews. Second, in two manufacturing companies, stakeholder
based models will be developed through interviews and focus groups with senior
management, frontline workers, and frontline supervisors. Participants will be
asked about the RTW process in general and more targeted questions regarding
influential components. Participants will also be led through a reference mode
exercise where they will be asked to estimate the direction, shape and magnitude
of relationships between influential components. Data will be entered into the
software program Vensim that provides a platform for visualizing system-structure
and simulating the effects of adapting components. Finally, preliminary model
validity testing will be conducted to provide insights on model generalizability
and sensitivity. EXPECTED IMPACT OF THE STUDY FOR PUBLIC HEALTH: The proposed
methodology will create a SDM of the RTW process using feedback relationships of
influential components. It will also provide an important simulation tool to
understand system behaviour that underlies complex RTW cases, and examine
anticipated and unanticipated consequences of disability management policies.
Significance for public healthWhile the incidence of occupational injuries and
illnesses has declined over the past two decades, the proportion resulting in
sickness absence has actually increased. Implementing strategies to address
sickness absences and promote return-to-work (RTW) can significantly benefit
physical and mental health, and work outcomes like worker engagement, job
satisfaction and job strain. As a key social determinant of health, participation
in paid work can also ensure that work-disabled individuals generate income
necessary for access to housing, education, food, and social services that also
benefit health. Improving RTW outcomes can also have significant societal
benefits such as a reduction in workers compensation costs, increased economic
activity and less burden on social assistance programs. Despite its benefits,
returning to work after injury or illness is not a straightforward process and
can be complicated by the individual, psychosocial, organizational and regulatory
components that influence a disabled person's ability to resume work activities.
PMID- 26425499
TI - Medically Assisted Procreation and Fast-Moving Developments in Science and Law:
Ethical and Legal Issues in Heterologous Procreation in Italy.
AB - Significance for public healthContinual scientific progress is making new
applications available, with significant medical, ethical, legal and social
implications, not only for the persons directly concerned. In the area of
medically assisted procreation, the use of heterologous techniques is able to
overcome problems of sterility or infertility for those requesting access to
methods of this kind. On the other hand, legislation is required to regulate the
many correlated issues, also with regard to other parties such as ova or sperm
donors and the offspring resulting from the use of these techniques: the
protection of the health of the offspring; the management of laboratory results
obtained during donor selection tests; the protection of confidentiality; the
donor-child traceability; the number of donations; and individuals' rights to be
fully informed about their biological origins are just some of the questions
confirming that the implications of new procreation techniques are not restricted
merely to the couples who access them.
PMID- 26425500
TI - Barriers and Facilitators to Palliative Care of Patients with Chronic Heart
Failure in Germany: A Study Protocol.
AB - BACKGROUND: Despite its high prevalence, similar symptoms and symptom burden,
people suffering from chronic heart failure receive less palliative care than
patients with malignant diseases. Internationally, numerous barriers to
palliative care of patients with chronic heart failure are known, however, there
are no credible data regarding barriers and facilitators to palliative care of
people suffering from chronic heart failure available for Germany. DESIGN AND
METHODS: Tripartite study. First part of this study evaluates health care
providers' (physicians and nurses) perceived barriers and facilitators to
palliative care of patients with chronic heart failure using a qualitative
approach. At least 18 persons will be interviewed. In the second part, based on
the results of part one, a questionnaire about barriers and facilitators to
palliative care of patients with chronic heart failure will be designed and
applied to at least 150 physicians and nurses. In the last part a classic Delphi
method will be used to develop specific measures to improve the palliative care
for chronic heart failure patients. EXPECTED IMPACT FOR PUBLIC HEALTH: The
results of this study will help to understand why patients with heart failure are
seldom referred to palliative care and will provide solutions to overcome these
barriers. Developed solutions will be the first step to improve palliative care
in patients with heart failure in Germany. In addition, the results will help
health care providers in other countries to take action to improve palliative
care situations for heart failure patients. Significance for public
healthPatients with chronic heart failure suffer from similar symptoms and
symptom burden than patients with malignant diseases. However, palliative care
differs between these groups in a quantitative and qualitative way. This study
will help to understand why patients with chronic heart failure receive less
palliative care than patients with malignant disease. In addition, measures to
overcome barriers and to promote facilitators of palliative care in patients with
chronic heart failure will be developed. These recommendations could provide a
basis for quality improvement projects or studies aiming at improving symptoms
and symptom burden of heart failure patients. The recommended measures could also
be used to reduce caregiver burden.
PMID- 26425502
TI - Food and Human Behaviour: Consumption, Waste and Sustainability.
PMID- 26425503
TI - Endoscopic ultrasonography-guided portal injection chemotherapy for hepatic
metastases.
AB - INTRODUCTION: We hypothesized that endoscopic ultrasonography-guided portal
injection chemotherapy (EPIC) using irinotecan-loaded microbeads may achieve
increased intrahepatic concentrations, while decreasing systemic exposure. This
may achieve enhanced efficacy for the treatment of diffuse liver metastases,
while decreasing systemic toxicities. MATERIALS AND METHODS: In eight
anesthetized 35 kg pigs, EPIC was performed transgastrically using the linear
array echoendoscope and a 22 g fine-needle aspiration. In four animals,
irinotecan (100 mg) loaded onto 75-150 micron liquid chromatography (LC) beads
was injected. In four animals, saline was injected into the portal vein and
unloaded irinotecan (100 mg) was injected into the jugular vein. Plasma (every 15
min), and at 1 h bone marrow, liver and skeletal muscle samples were obtained.
Irinotecan and SN-38 (active metabolite) concentrations were assayed by LC/mass
spectrometry. RESULTS: The procedure was performed safely in all eight animals.
Compared with systemic administration, EPIC resulted in almost twice the hepatic
concentration of irinotecan (6242 vs. 3692 ng/g) and half the systemic
concentrations in plasma (1092 vs. 2762 ng/mL), bone marrow (815 vs. 1703 ng/mL)
and skeletal muscle (521 vs. 1058 ng/g). SN-38 levels were lower with EPIC
(liver: 166 vs. 681 ng/g; plasma: 1.8 vs. 2.4 ng/mL; bone marrow: 0.9 vs. 1.4
ng/mL; muscle 4.6 vs. 9.2 ng/g). Liver histology showed the beads within small
portal venules. CONCLUSIONS: EPIC using irinotecan-loaded microbeads can enhance
hepatic exposure to irinotecan, while decreasing systemic concentrations. SN-38
levels were lower with EPIC indicating that a substantial portion of the
irinotecan was still loaded onto beads. The microbeads may act as a reservoir
resulting in prolonged hepatic drug exposure.
PMID- 26425501
TI - H1N1 Influenza Pandemic in Italy Revisited: Has the Willingness to Get Vaccinated
Suffered in the Long Run?
AB - BACKGROUND: The aim of the study is to assess the long-term secondary effects of
personal experience with the H1N1 pandemic of 2009/2010 and the perception of the
institutional reaction to it on Italians' willingness to get vaccinated in case
of a novel influenza pandemic. DESIGN AND METHODS: We conducted 140 face-to-face
interviews in the Registry Office of the Municipality of Milan, Italy, from
October to December 2012. RESULTS: Willingness to get vaccinated during a novel
influenza pandemic was best predicted by having been vaccinated against the
seasonal flu in the past (OR=5.18; 95%CI: 1.40 to 19.13) and fear of losing one's
life in case of an infection with H1N1 (OR=4.09; 95%CI: 1.68 to 9.97). It was
unaffected by the assessment of institutional performance. CONCLUSIONS: The
findings of this study do not point to long-term secondary effects of the
institutional handling of the H1N1 pandemic. The results highlight the fact that
behavioural intention is not the same as behaviour, and that the former cannot
simply be taken as an indicator of the latter. Significance for public
healthWhereas influenza pandemics occurred rather rarely in the last centuries,
their frequency can be expected to increase in the future due to the enhanced
globalisation and still raising importance of air travelling. Recent examples
(Ebola, H1N1, SARS, avian influenza) demonstrate that initially local disease
outbreaks often become worldwide health threats of international concern.
National and international health authorities are consequently urged to present
preparedness plans on how to manage such health crises. However, their success
highly depends on their acceptance by the public. To ensure the public compliance
with recommended actions, effective communication is needed. Since communication
is most successful when it meets the needs of the target audience, a full
understanding of the audience is crucial. This study can help public health
experts to better understand the variables determining people's willingness to
get vaccinated during influenza pandemic, in terms of behavioural and perceptual
variables. This knowledge enables them to correctly address the public's concerns
when having to communicate during the next outbreak of pandemic influenza.
PMID- 26425504
TI - Characteristics of vessels wall, myocardium and epicardial fat in patients with
heart failure with preserved ejection fraction with and without metabolic
syndrome.
AB - BACKGROUND: The structure of the vessels wall and myocardium is an independent
predictor of cardiovascular events among patients with heart failure (HF). There
is a data that metabolic syndrome (MS) accelerates the progression of structural
and functional disorders of the vessel wall and myocardium. Epicardial fat
thickness was shown to correlates with visceral fat thickness and to be an
independent predictor of cardiovascular diseases. OBJECTIVES: To investigate the
characteristics of vessels wall, myocardium and epicardial fat in patients with
HF with preserved ejection fraction (HF-PEF) with and without MS. MATERIALS AND
METHODS: A total of 59 patients with HF-PEF were included. First group - patients
without MS (n = 29), second group - patients with MS (n = 30). Following
characteristics were evaluated: Arterial stiffness (stiffness index [SI]),
reflection index (RI), augmentation index (Alp). The function of big vessels was
evaluated by phase shift (PS), of the small vessels - by the occlusion index
(OI). Investigations were performed by the device "angioscan." Sizes of the heart
chambers and the thickness of the myocardium wall and epicardial fat thickness
were evaluated echocardiographically. RESULTS: Among the patients from both
groups significant changes of the vessels wall and myocardial structure were
found. SI at the first group was 8.26 +/- 1.72 m/s, at the second group - 9.62 +/
5.61 m/s (non-significant, P = 0.25). RI at the first group was 39.79 +/-
18.12%, at the second - 31.43 +/- 17.23% (non-significant, P = 0.086). Alp at the
first group was 23.47 +/- 14.69%, at the second - 11.16 +/- 17.14% (significant,
P = 0.011). PS at the first group was 8.05 +/- 7.72 ms, at the second - 5.34 +/-
4.4 ms (non-significant, P = 0.36). OI at the first group was 1.34 +/- 0.58%, at
the second - 1.46 +/- 0.54% (non-significant, P = 0.46). Significant intergroup
differences were found in the interventricular septum thickness: 10.3 +/- 1.2 mm
at the first group and 11.3 +/- 1.6 mm at the second (P = 0.01); left ventricle
wall thickness: 10.1 +/- 1.1 mm at the first group and 11.3 +/- 1.6 mm - at the
second (P = 0.001); left ventricle myocardium mass: 157.75 +/- 46.11 g at the
first group and 201.19 +/- 58.82 g - at the second (P = 0.005). The epicardial
fat thickness was 14.8 +/- 1.8 mm at the first group and 36.7 +/- 1.7 mm - at the
second group (significant, P = 0.001). CONCLUSION: Among patients with
hypertension and HF-PEF with and without MS significant changes in the structure
of the vessel wall and myocardium were found. The presence of MS lead to more
pronounced myocardial remodeling. The epicardial fat thickness is significantly
higher among patients MS.
PMID- 26425505
TI - Metallic stent in the endoscopic treatment of pancreatic fluid collections.
AB - BACKGROUND AND AIMS: The endoscopic treatment of pancreatic fluid collections
(PFCs) has become the preferred first-line approach. Fully covered self
expandable metal stents (FCSEMS) were considered as an alternative to multiple
double pigtail stents. The aim of this study was to evaluate the results of the
endosonography guided drainage (EUS-GD) of PFCs with FCEMS. MATERIALS AND
METHODS: A total of 33 consecutive patients were included. Cystogastrostomy and
cystoduodenostomy were created with a linear echoendoscope under endosonographic
and fluoroscopic control. Procedures were performed in a standard way of,
puncture with a 19 gauge needle, bougie dilation and insertion of FCSEMS.
RESULTS: A total of 33 patients (mean age 52 years, 21 men, range: 18-77 years),
were included. PFCs were 22 non-infected symptomatic pseudocyst and 11 walled-off
necrosis or abscess. EUS-GD was successful in 30 (90.9%) patients. Stent
insertion failed in one patient. Two patients needed surgery. Complications were
observed in 8 (25%) patients (stent dislocation in 3, perforation in 2, bleeding
in 2 and pneumoperitoneum in 1 patient). Procedure related mortality was not
seen. The mean cyst size was 11.3 cm (5-22). FCSEMS were successful in the
treatment of pseudocysts (after 1 month mean cyst size is 6.2 cm, range: 0-15 cm,
with 54.8% decrement rate). During a mean follow-up of 15 months complete
resolution was 66.6% (20 patients) and recurrence due to stent malfunction was
10%. All these cases were submitted to a new session of endoscopic drainage.
CONCLUSIONS: EUS-GD, FCSEMS insertion provides an effective, minimally invasive,
and safe approach in the management of PFCs.
PMID- 26425506
TI - Endosonographic features of unicentric Castleman Disease.
AB - BACKGROUND: Castleman disease (CD) is a rare lymphoproliferative disorder most
frequently occurring in the mediastinum. Peripancreatic forms are less frequent.
Few cases of endoscopic ultrasonography-fine-needle aspiration (EUS-FNA) findings
of this lesion have been reported, where no real-time tissue elastography (RTTE)
has been described in the literature to our knowledge. METHODS: We describe the
endosonographic, elastographic, cytologic and immunocytochemistry findings in two
cases of unicentric CD of the hyaline vascular variant. RESULTS: Two females,
aged 41 and 34 year were referred to our hospital for further EUS evaluation of a
peripancreatic mass found incidentally on computed tomography. EUS examination
revealed around, well-demarcated, uniformly hypoechoic mass measuring 52 and 23
mm respectively, with smaller adjacent hypoechoic lymph nodes. Doppler
examination revealed intense peripheral vascularity, together with prominent
penetrating feeding vessels entering a distinct hilum. RTTE revealed a relatively
homogenous soft elastographic pattern. EUS-FNA provided smears with clusters of
lymphocytes in a hemorrhagic background. Cell block preparation showed immature
lymphocytes surrounding lymphocyte-poor centers with vascular proliferation.
Immunohistochemical staining of the cell block sections showed CD45-leukocyte
common antigen, CD20, CD23, CD79a, Bcl-2 and CD5 positivity in small lymphocytes.
Cytology was suggestive of non-Hodgkin's lymphoma. Surgical excision was
performed in both cases and histopathology was consistent with CD of the hyaline
vascular type. CONCLUSION: The echo features of a solitary hypoechoic homogenous
well-demarcated mass with prominent vasculature and increased elasticity should
raise the possibility of unicentric CD. EUS-FNA usually cannot make a definitive
distinction from certain kinds of lymphoma.
PMID- 26425508
TI - Liver abscess as a first manifestation of colonic tumor.
AB - INTRODUCTION: Male, 72-year-old, morbidly obese, diabetic, admitted for abdominal
pain, prostration and fever that started last 3 days. Abdominal ultrasound and
abdominal computed tomography scan showed liver injury in the transition of V and
VI segments measuring 8.4 cm. Due to the possibility of liver abscess, initiate
empirical antibiotic therapy with ampicillin and sulbactam and metronidazole and
performed ultrasound-guided percutaneous drainage of liver injury. Negative for
malignant cells, with the presence of leukocytes and negative culture. After 2
weeks of treatment, take control image without changing the lesion dimension. New
percutaneous drainage with the same results. We opted for performing endoscopic
ultrasound (EUS) with fine-needle aspiration (FNA). FNA pathology: Moderately
differentiated adenocarcinoma. Immunohistochemistry suggestive of metastasis of
the lower gastrointestinal tract. Due this finding, realized colonoscopy, which
revealed a vegetating lesion with central ulceration, bleeding, filling almost
the entire cecum. Patient was referred for surgical resection of the bowel tumor,
which showed moderately differentiated adenocarcinoma infiltrating vegetative and
possibly originated from villous adenoma with high-grade dysplasia. DISCUSSION:
The finding of metastatic liver abscess of colonic neoplasia is not common. In
most cases, the material from the abscess drainage allows the diagnosis, but in
this case, even after two ultrasound-guided percutaneous drainage was not
obtained conclusive bacteriological or histopathological. Opted for new puncture
through EUS, which allowed definitive diagnosis of the condition. CONCLUSION:
Metastatic colon neoplasm should be considered in cases of differential diagnosis
of liver abscess.
PMID- 26425507
TI - Endoscopic ultrasonography-fine-needle aspiration of solid pancreatic lesions: A
prospective, randomized, single-blinded, comparative study using the 22 Gauge
EchoTip(r) ProCoreTM HD (A) and the 22 Gauge EchoTip(r) Ultra HD (B) endoscopic
ultrasound needles.
AB - INTRODUCTION: In order to improve diagnostic efficacy of pancreatic masses, a new
endoscopic ultrasonography-fine-needle aspiration (EUS-FNA) needle was developed
(EchoTip((r)) ProCoreTM HD). Very few studies have compared these two needles and
none could avoid selection biases. AIMS: The present study intends to compare the
results obtained by these two needles when performing EUS-FNA of pancreatic solid
lesions. PATIENTS AND METHODS: This was a prospective, single-blinded,
randomized, controlled trial conducted at a tertiary care referral center. Thirty
consecutive patients with solid pancreatic lesions were enrolled to have EUS-FNA
performed with two different types of needle. All patients were punctured with
the two needles and were randomized regarding the order of the needle to be used.
RESULTS: After collecting data, we used the Fisher's exact test in order to
compare the results P <0.05. There was no difference (P = 1.0) regarding
introduction, exposition and removal of the needles. The values of sensitivity
(92% for needles A and B), specificity (100% * 80%), positive predictive value
(100% * 95.8%), negative predictive value (71.4% * 66.6%) and accuracy (93.3% for
needle A and 90% for needle B) were not statistically different. The duration of
the procedure was the only analyzed parameter, in which we observed a difference
between the needles. For needle A, the average time was 2 min 26 s (1 min 30 s-4
min 0 s) and for needle B the average time was 11 min 7 s (6 min 0 s-17 min 0 s).
CONCLUSION: Even though, the 22 gauge EchoTip((r)) ProCoreTM HD and the 22 gauge
EchoTip((r)) Ultra HD endoscopic ultrasound needles had similar overall results,
the ProCoreTM needle allowed a much quicker procedure.
PMID- 26425509
TI - Diagnosis of ganglionar tuberculosis by endoscopic ultrasonography.
AB - INTRODUCTION: The endoscopic ultrasonography (EUS) is an endoscopic technique of
proven clinical validity today, having a significant impact on the diagnosis and
evaluation of several diseases with a low complication rate. The EUS-fine-needle
aspiration (FNA) allows the evaluation of subepithelial lesions, extra-luminal
lymph nodes or the gastrointestinal tract that are difficult to access by other
methods with safe and high diagnostic accuracy. AIMS AND METHODS: In the case
reported, the EUS-FNA was useful for the differential diagnosis with residual
biliary microlithiasis and the diagnosis of non-oncologic pathology. RESULTS:
Male, white, 35-year-old, human immunodeficiency virus and tuberculosis treatment
for about 5 months presented with jaundice. No fever, weight loss or abdominal
pain. Choluria and hipocholia. History of cholecystectomy for about 1 year due to
cholelithiasis. Laboratory tests showed cholestatic jaundice (direct
hyperbilirrubinemia). Abdominal ultrasound showed liver without particularities,
without biliary dilatation or filling defects. Initially suspected hepatitis due
tuberculosis drugs so, the treatment was suspended. After a week with no drugs,
no improvement in jaundice was observed. In contrast, a progressive increase
indirect bilirubin. EUS performed with identification of mass along the distal
common bile duct near the duodenal papilla. FNA performed with the presence of
lymphocytes and tuberculosis bacile positive. After, endoscopic retrograde
cholangiopancreatography was performed with sphincterotomy and placement of
endoprosthesis for biliary drainage. The tuberculosis drugs were restarted with
the plan to complete. The jaundice was resoluted. The patient completed 9 months
of treatment and abdominal tomography has not identified a mass in that place.
CONCLUSION: The EUS-FNA was proven to be a useful tool for diagnosis of non
oncologic pathologies like tuberculosis.
PMID- 26425510
TI - Solid pancreatic lesions: The choice of fine-needle aspiration-needle to optimize
the diagnosis.
AB - INTRODUCTION: Endoscopic ultrasonography (EUS)-guided fine-needle aspiration
(FNA) have a better accuracy for the detection of pancreatic tumors compared with
others images modalities. We assessed if the image criteria of elastography and
contrast harmonic echo-endoscopic ultrasound could help in choosing the
appropriate FNA-needle in the evaluation of focal pancreatic mass in other to
maximize the diagnostic yield. This study prospectively included all new patients
with focal pancreatic masses referred to be examined by EUS from October to
December/2013. A total of 21 patients performed EUS with sequentially
elastography and intravenous injection of a second-generation contrast agent (2.4
mL of SonoVue, Braco International, The Netherlands). The lesions which appear
hipovascular were assessed with 22 gauge or 25 gauge FNA-needles. The
hipervascular masses were biopsied with 19 gauge needles. RESULTS: The topography
of the lesions varied on 13 at the head, 4 at the body and 1 on the tail. The
finding of a hypoenhanced mass was found in 57% (12/21 patients). Hyperenhanced
was detected in 28% (6/21 patients). There were 14% (three patients) which the
data were not recorded. The cytological diagnosis was achieved in 81% (17/21
patients) on the first biopsy. The others four patients have reached the
diagnosis on the second examination. Of those four patients, in one was used the
ProCore 25 gauge (lesion on the uncinatus process), and another one was used both
22 gauge and 25 gauge in the first examination. CONCLUSION: A characterization of
the pancreatic lesions with elastography and contrast agents might be useful for
clinical decision of which needle is better to improve biopsy quality and
minimize EUS-FNA negatives results.
PMID- 26425512
TI - Feedback is the best way to see.
AB - A 60-year-old man with past history of acute mild pancreatitis (AP) in 1997 and
2005, recently with repeated attacks of AP 5 times in last 2 years. Repeated
endoscopic ultrasonography (EUS) showed 20 mm cyst in pancreatic body with 5 mm
nodule, main pancreatic duct (MPD) 4-6 mm, fine-needle aspiration malignant cell
negative, mucin positive. Computed tomography and magnetic resonance imaging of
branch duct intraductal papillary mucosal neoplasms with 10 mm branch duct. From
2011 to 2013, the cyst was without progression in size or character. Due to
clinical course of repeated AP, endoscopic retrograde cholangiopancreatography
was recommended. It revealed dilated MPD 5-7 mm and 15 mm * 13 mm cyst in
pancreatic body. Distal pancreatectomy was indicated because of clinical course
and "worrisome EUS features" - MPD size and intramural nodule. In terms of having
feedback, endosonographer use to examine every resected specimen of pancreas in
our hospital just after surgery. The resected body with "sand glass" appearance
of the cyst of size 3 cm was totally different from what we saw previously. We
rewinded the previous EUS documentation and made a new evaluation. EUS is unique
method for pancreatic tumors, but only in combination with real image of specimen
makes endosonographer to bow up.
PMID- 26425511
TI - Vascular image in autoimmune pancreatitis by contrast-enhanced color-Doppler
endoscopic ultrasonography: Comparison with pancreatic cancer.
AB - INTRODUCTION: In autoimmune pancreatitis (AIP), veins of various sizes are highly
affected by obliterative phlebitis without damage to arteries, in contrast, the
involvement of both arteries and veins is observed in the mass of pancreatic
cancer. A vascular image without blooming artifact in the pancreas is clearly
observed in the directional eFLOW (Prosound alpha10, Aloca Co., Tokyo, Japan)
color mode using contrast-enhanced color-Doppler endoscopic ultrasonography (CC
EUS) despite perfusion of the contrast media. AIMS AND METHODS: The aim of this
study was to compare the vascular structure of AIP with that of pancreatic cancer
using CC-EUS. We evaluated the perfusion image and the vascular image of the mass
in AIP patients (11) with an increase in serum IgG4 levels (477.3 +/- 314.2
IU/mL) and in pancreatic cancer patients (11) with elevated serum CA19-9 levels
(49839.0 +/- 80061.6 mg/dl), on CC-EUS. Perfusion images were obtained at 20-30 s
after injection of a contrast agent, Sonazoid (GE Healthcare AG, Oslo, Norway),
by extended pure harmonic detection mode and were assessed as to homogeneity or
heterogeneity (containing partial low echoic areas or multiple spotty low echoic
areas) enhancement. The vascular image was assessed in the directional eFLOW
color mode despite perfusion of the contrast media (40-50 s after injection of
Sonazoid) as to the presence of a dendritic vessel network or only a few feeder
vessels. The parameters for imaging were as follows: Mechanical index, 0.22-0.24;
transmission frequency, 5.0 MHz; and receiving frequency, 5.0 MHz. The Chi-square
test or Fisher's exact test was used for comparison of categorical data of the
two groups when appropriate. This study was approved by the institutional review
board of Sendai City Medical Center. All subjects gave informed consent. RESULTS:
A homogenous pattern in perfusion imaging was seen in 73% of patients with AIP
(8/11) and 55% of those with pancreatic cancer (6/11). The rates were not
significantly different between the two groups (P = 0.33). In the other patients
with a heterogenous pattern, multiple spotty low echoic areas were seen in 33%
(1/3) and 80% (4/5) in each group, respectively. A dendritic vascular pattern in
the eFLOW color mode was seen in 82% (9/11) of patients with AIP, but was not
seen in any of patients with pancreatic cancer. The other patients with AIP (18%)
and all patients with pancreatic cancer showed only a few feeder vessels in the
mass on CC-EUS. CONCLUSION: The eFLOW color mode using Sonazoid may be useful for
evaluating the vascular structure of AIP for differential diagnosis from
pancreatic cancer.
PMID- 26425513
TI - Short-term results after hepaticogastrostomy guided by echo-endoscopy:
Monocentric retrospective study.
AB - BACKGROUND: Biliary drainage guided by echo-endoscopy (EUS) is a recent technique
but expanding more and more in addition of retrograde and percutaneous
approaches. METHODS: Seventy-three hepaticogastrostomy (HG) were carried out from
2000 to 2013. After exclusion of patients included in a randomized prospective
study, data from 60 patients were retrospectively analyzed in order to study the
feasibility and early results of this technique. RESULTS: During the study
period, 60 patients (woman = 32; median age = 64 years [38-93]) were treated by
HG. This technique was choose in the event of impossibility to reach the papilla,
a failure of endoscopic retrograde cholangiopancreatography or to achieve
drainage of the left hepatic biliary ducts in 35%, 15% and 50%, respectively. The
biliary stricture was neoplasic in 85%. Sixty-four procedures were carried out:
The technical success rate was 94%. Eighteen patients presented one or more
adverse effects (28%) including: Infection (n = 14), pneumoperitoneum (n = 7),
choleperitoneum/bilioma (n = 8), hemorrhage (n = 2), other (n = 2). Seven stents
migration occurred (11%). The average duration of hospitalization was 9 days (0
61j). Three related deaths occurred, due to severe infection. During the period
of the study, several types of stent were placed during the first procedure:
Plastic stent (n = 12), one covered or uncovered metallic stent (n = 9),
association of one uncovered metallic stent and one fully covered stent (SIS, n =
27), or one half covered metallic stent (n = 16). The rate of complications was
respectively 33% (n = 4), 56% (n = 5), 26% (n = 7) and 13% (n = 2) according to
the type of stent used. Three successive periods can thus be individualized
according to the type of biliary stent used and the use of the CO2 insufflator
[Table 1]. [Table: see text]. CONCLUSIONS: Hepaticogastric anastomosis guided by
echo-endoscopy is an effective, useful technique when the retrograde way is not
possible or to drain selectively left intrahepatic biliary ducts. The morbidity
rate is quite high but seems to decrease.
PMID- 26425514
TI - Safety and efficacy of nitrous oxide for endoscopic ultrasound procedures that
need irrigation.
AB - OBJECTIVE: Echo-endoscopes are much stiffer and thicker than regular endoscopes.
During the procedure of endoscopic ultrasound (EUS) procedure, water irrigation
is a very useful for imaging but very dangerous if the patient receive the
procedure under anesthesia without intubation. In this study, we evaluated the
safety and effectiveness of nitrous oxide (N2O) (<=70%) for EUS. METHODS: Among
4230 patients who underwent EUS from December 2012 to December 2013, 347 out
patients who need irrigation during the procedure were enrolled and divided into
Group A. Group A (N2O sedation group, n = 162) and Group B (no sedative group, n
= 185). For Group A, patients received N2O by inhalation during the procedure.
The mixture rate of N2O and O2 was 45-65% and controlled by nurses according to
individual effect. The cardiorespiratory functions, procedure duration,
complications, and visual analog scale (VAS) of the patient and examiner
satisfaction were compared. RESULTS: Both group had comparable diagnostic
accuracy, but VAS of the patients who received N2O sedation was higher than that
in Group B (7.5 vs. 4.5, P < 0.05) and the examiner procedural satisfaction
ratings of Group A was also better than that of Group B (8.1 vs. 5.1, P < 0.05);
Most patients in Group A reported willingness to reconsider N2O for a future EUS.
No pulmonary aspiration occurred in this study. CONCLUSIONS: N2O for EUS is
comfortable, safe and feasible, especially for the procedures that need
irrigation.
PMID- 26425515
TI - Interobserver concordance for endoscopic ultrasonography-guided fine-needle
aspiration on-site cytopathology.
AB - INTRODUCTION: Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA)
is an accurate method of diagnosing and staging gastrointestinal and thoracic
malignancy. A key issue in maximizing FNA accuracy is to ensure that an adequate
specimen is obtained. On-site cytopathology increases the diagnostic yield of EUS
FNA. However, this increases the time and costs. Physicians trained in EUS and in
pathology are capable of interpreting cytologic adequacy from EUS-FNA specimens.
Furthermore, on-site interpretation by the endoscopist could reduce cost and
procedure duration. The learning curve of endossonographers in on-site
cytopathology and how they could contribute in EUS-FNA accuracy increase is
unknown. OBJECTIVE: To determine the interobserver concordance of on-site
cytopathology interpretation of EUS-FNA specimens by comparing endosonographers
trained in cytology with a physician cytopathologist. METHODS: A prospective
blinded study comparing one endossonographer with one physician cytopathologist.
The study was developed in the Santa Casa Medical School, Brazil from February to
November 2012. Fifteen different cases of EUS-FNA were analysed, in a total of 50
slides. Each observer described the slides for the adequate or not of tissue
sampling, and classified as benign, suspicious, malign or undefined. The analyses
were then matched. RESULTS: We analyzed the concordance of 50 slides description
made by the endossonographer and physician cytopathologist, according to enough
material, cellular group identification and final diagnosis. Kappa (kappa)
indexes were: Presence of material kappa = 0.480 (P < 0.001); presence of
malignance kappa = 0.808 (P < 0.001); in subepithelial lesions kappa = 0.615 (P =
0.06); in pancreatic lesions kappa = 0.675 (P < 0.001); in mediastinal lesions
kappa = 0.243 (P = 0.128). CONCLUSION: Our study showed that endosonographers and
cytopathologists had good concordance in EUS-FNA specimens on-site cytopathology
interpretation, except in mediastinal/pulmonary cases.
PMID- 26425516
TI - Relevance of endoscopic ultrasound in the management of esophagus cancer therapy.
AB - INTRODUCTION: The objective of this case series study by retrospective analysis
was to determine the relevance of endoscopic ultrasound (EUS) in therapeutic
decision esophageal cancer. MATERIAL AND METHODS: Using medical records of the
Department of Endoscopy of Santa Casa de Sao Paulo, we have collected data from
16 patients, in 4 years, diagnosed of esophageal cancer, and presented in the
form of clinical cases to a specialist surgeon in esophageal cancer and a
clinical oncologist, for therapeutic evaluation before and after the outcome of
EUS. RESULTS: Both of them choose non-resective and not curative methods (68.8%
by surgeon vs. 87.5% oncologist) before EUS. The best treatment by the surgeon
was chemotherapy and palliative radiotherapy associated (25%) and palliative
endoscopic prostheses (25%), and by the oncologist, neoadjuvant chemotherapy and
radiotherapy associated (56.2%). After EUS, the resective surgical treatment was
the both choice in only 6.2% of cases, and the rest of 93.8%, non-resective. The
surgeon choice was chemotherapy and palliative radiotherapy associated (44%), and
oncologist choice was neoadjuvant chemotherapy and radiotherapy associated (44%).
Analysis by the Chi-square method, comparing respective versus non-resective
treatment, surgeon versus oncologist, with and without the EUS, obtained values
of P = 0.39 and P = 0.46, respectively. The comparison between healing and non
healing treatment had the same P value. Regarding the change in behavior
(resective vs. non-resective), there was a change of approach by the surgeon in
25% of cases (P = 0.17) and the oncologist moved conduct in 6.25% of cases.
Comparing the changing of behavior among experts, the P value was 0.33. Despite
evidence of behavior change after the EUS, the statistical point of view, the P
value had no significant relevance. The main factor involved is probably due to a
reduced number of sample cases. However, this is a pilot study, and is needed
other with a larger number of cases. CONCLUSION: The data obtained allow us to
conclude that EUS proved to be an important test for the change in staging and
therapeutic management of esophageal cancer.
PMID- 26425517
TI - Influence of layer, size and organ of subepithelial lesions of upper
gastrointestinal tract in outcomes of endoscopic ultrasound-guided fine-needle
aspiration.
AB - INTRODUCTION: The endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)
has emerged as a minimally invasive and safe method for material procurement in
the differential diagnosis of subepithelial lesions (SEL) of upper
gastrointestinal tract (UGT), especially in suspicious lesions of
gastrointestinal stromal tumors (GIST). There are few studies discussing the
factors that influence the EUS-FNA in the diagnosis of SEL. AIM: To establish
possible associations between lesion size, layer and organ of origin with the
outcome of EUS-FNA in patients with SELs of UGT. METHODS: A retrospective
analysis using data of patients referred to French-Brazilian Center of EUS of
endoscopy Department of Santa Casa de Sao Paulo Hospital, with previous
endoscopic diagnosis of SEL, which underwent EUS-FNA from May 2006 to August
2011. RESULTS: A total of 222 patients were submitted to EUS. 15 with extrinsic
compressions and 207 with SEL. Of these, 89 underwent to EUS-FNA. Ninety-two SEL
were diagnosed on EUS and punctured. The EUS-FNA was positive in 58.7%. In
lesions measuring 2-3 cm and >3 cm, the EUS-FNA was positive in 80% and 72%,
respectively (P < 0.001). CONCLUSION: The size of SELs was the only variable that
influenced the outcome of EUS-FNA. Best results are achieved in lesions larger
than 2 cm.
PMID- 26425518
TI - Imaging of peritoneal ligament by endoscopic ultrasound.
AB - INTRODUCTION: Double layered peritoneal folds, variously named as ligaments,
omenta and mesenteries connect the intraperitoneal organs to the abdominal wall.
Some of these ligaments contain blood vessels and lymph nodes while others are
avascular. The peritoneal folds not only act as conduits for the passage of blood
vessels from the retroperitoneum to reach intraperitoneal organs, but also
provide a pathway for the spread of disease processes. It is difficult to
identify these normal peritoneal folds at imaging. Computed tomography is the
most common imaging modality used to detect diseases of the peritoneum to fully
delineate peritoneal anatomy and the extent of disease. The endoscopic ultrasound
(EUS) can be used to image peritoneal ligaments with the advantage of lack of
ionizing radiation and lower cost. Though EUS is being increasingly used both for
diagnostic and interventional purposes in the abdomen, it has not been used to
assess the peritoneal ligaments till now. METHODS: We did this study in 50
patients using linear echo endoscope to delineate various peritoneal ligaments.
The technique of evaluation of ligament has been described in this review.
CONCLUSION: The peritoneal ligaments can be delineated with accuracy by EUS.
PMID- 26425519
TI - To evaluate the role of novel fully covered self-expanding metal stent for
endoscopic drainage of infected pancreatic pseudocyst.
AB - INTRODUCTION: Endoscopic ultrasonography-guided transgastric drainage of
pancreatic pseudocyst (PPC) is the mainstay of treatment. Drainage can be
achieved either by plastic stents or fully covered self-expandable metal stent
(FCSEMS). Plastic stents have small lumen diameter, which may limit drainage and
may necessitate re-intervention. FCSEMS are easier to deploy and preclude the
need to place multiple plastic stents. OBJECTIVE: To evaluate the role of novel
FCSEMS for endoscopic drainage of infected PPC. METHODS: PATIENTS: 10 patients
with single symptomatic pseudocyst in proximity to the stomach or duodenum and
fever were treated. Pseudocyst drainage was done per protocol. Repeat computed
tomography scan after 72 h. Nasocystic drain removed after 3-5 days. PATIENTS
were followed-up at every 2 week interval. Stent was removed after complete
disappearance of pseudocyst confirmed on imaging. Early (7 days) and late (>7
days) complications were noted and managed accordingly. RESULTS: Technical
success and clinical success achieved in all. Early complication: 1/10
(pneumoperitoneum). No late complications observed. Stent were removed without
complication after 6-7 week follow-up period ranges from 6 to 8 months.
CONCLUSION: Use of FCSEMS for pseudocyst drainage is technically feasible and
safe.
PMID- 26425520
TI - A rare cause of hemosuccus pancreaticus diagnosed with endoscopic ultrasound.
AB - INTRODUCTION: Hemosuccus pancreaticus (HP), hemorrhage from the papilla of Vater
through the pancreatic duct (PD), is a rare cause of upper gastrointestinal
bleeding. It may be caused by chronic pancreatitis, pseudoaneurism and pancreatic
tumors. Only 2% of HP involves the hepatic arteries. Endoscopic ultrasound (EUS)
may not only visualize the presence of HP, previously seen on computed
tomography/magnetic resonance imaging (CT/MRI), but also reveal additional
pathology. CASE REPORT: A 62-year-old man was admitted with severe intermittent
gastrointestinal bleeding. He underwent gastroscopy, colonoscopy and capsule
endoscopy without sign of bleeding. The patient had no previous history of
pancreatitis or infection. On CT and MRI scan with angiography, an aneurism of
the common hepatic artery (CHA) was found, with a dilatation of the main PD
toward the tail of the pancreas, but no apparent source of bleeding. EUS was then
performed, and could show a partial thrombosed aneurysm of a hepatica with a
diameter of 5 cm. In addition, a narrow fistula between the hepatic artery and PD
could be identified using power Doppler. The patient was subsequently operated,
which revealed a thrombosed arteriosclerotic aneurysm in the CHA with fistula to
the PD. CONCLUSION: To the best of our knowledge, this is the second reported
case of a severe gastrointestinal bleeding due to a fistula between the CHA and
PD. The use of EUS in diagnosing this rare condition has not been reported
before, but seems feasible.
PMID- 26425521
TI - Endoscopic ultrasonography-guided bi-lateral biliary drainage: A case series
study.
AB - INTRODUCTION: Biliary obstruction is preferentially managed by endoscopic
retrograde cholangiopancreatography (ERCP). However, after ERCP failed,
alternatives include percutaneous transhepatic drainage, surgery and more
recently, endoscopic ultrasonography (EUS)-guided hepaticogastrostomy. The
limitation of this technique is that the drainage is restricted to the left side.
The aim of this study is to describe a new method of drainage of both hepatic
ductal systems by hepaticogastrostomy in patients with hilar obstruction.
RESULTS: Nine prospectively patients were included, all with hilar obstruction
(metastasis of a pancreatic adenocarcinoma n = 4, cholangiocarcinoma n = 1,
gallbladder cancer n = 2 and metastasis from a pancreatic neuroendocrine tumor n
= 2). A total of four patients had previously Whipple surgery and the others five
had duodenal involvement by the tumor. The topography of the stenosis varied from
Bismuth type 2 (n = 7) and hilar infiltration in the others two. All of them were
submitted a three-step drainage. The first one consisted in a transgastric EUS
guided puncture of the left-side bile duct with a 19 gauge needle, insertion of a
0.0035 inch guide wire which was positioned at the right biliary tree crossing
the bile bifurcation. After a dilatation with 6 Fr cystotome, a non-covered self
expandable metal stent was placed communicating the right and left biliary ducts.
Finally, a second stent, partially covered, was inserted at the left biliary
duct, with the distal part inside the previously stent and the proximal edge
positioned at the stomach. Successful drainage was observed in seven patients,
two of them presented abdominal pain during the first 72 h. One patient developed
sepsis and death 7 days after the procedure and the other one had drainage
failure. Jaundice was reduced significatively in seven patients and a
chemotherapy was started in 6/7 patients. CONCLUSION: This pilot study shows the
feasibility of this new technique to drain the right biliary duct in patients
with hilar obstruction, with few major complications rates.
PMID- 26425522
TI - Endoscopic ultrasound guided confocal microscopy: Atlas of cystic pancreatic
lesions.
PMID- 26425523
TI - The observation of the formation of splenic artery pseudoaneurysms.
AB - Pseudoaneurysms are infrequent, potentially fatal angiopathies. Because of a high
mortality rate, pseudoaneurysms must be handled urgently, regardless of the size
and symptoms at presentation. We report a case of chronic pancreatitis and a
pseudocyst of the pancreas complicated with a splenic artery pseudoaneurysm.
Endoscopic ultrasonography (EUS) was chosen as the device to observe the forming
of a splenic artery pseudoaneurysm, which could provide timely, minimally
invasive, precise lesion information. Early diagnosis and urgent measure are
important when there is a high probability of splenic artery psedoaneurysm. In
recent years, EUS has been extensively studied in the detection, diagnosis and
treatment of pancreatic disease. The color-Doppler flow imaging (CDFI) can
dynamically reflect the peripheral blood flow signal. EUS with a CDFI function
can play an important role in the initial detection of pseudoaneurysms,
especially when complicated with chronic pancreatitis with or without a
pseudocyst. We recommend that EUS should be carried out if a pseudoaneurysm near
the digestive tract is considered, then effective and timely measures can produce
a favorable prognosis.
PMID- 26425524
TI - Epicardial fat as the predictor for essential hypertension and early vascular
damage in patients with metabolic syndrome and non-alcoholic fatty liver disease.
AB - Increased visceral adiposity is a new marker of metabolic syndrome, early
vascular damage, non-alcoholic fatty liver disease and also is associated with
essential hypertension. Epicardial adipose tissue is a very important factor in
the pathogenesis of coronary atherosclerosis. Hypertension is one of the most
important risk factor for the development of coronary heart disease, stroke,
congestive heart failure, and end-stage renal disease. Epicardial fat is an
active endocrine organ producing a wide range of active molecules, which can
affect vessels dramatically.
PMID- 26425525
TI - Endoscopic ultrasound-guided needle confocal laser endomicroscopy in pancreatic
masses.
AB - INTRODUCTION: Endoscopic ultrasound (EUS) is an established tool in diagnosing
pancreatic masses and enables guided fine-needle aspiration (FNA). Confocal laser
endomicroscopy (CLE) has allowed in vivo microscopic analysis during on-going
endoscopy. Recently, CLE has gone beyond luminal indications with the development
of a new microprobe (nCLE). The aim of this case series was to study the
feasibility of EUS-guided nCLE and to correlate the findings with microscopy.
METHODS: A total of 25 patients with pancreatic masses were included. During the
procedure, an nCLE fiber preloaded into a 19 gauge FNA needle was advanced into
the lesion under EUS guidance. Fluorescein was administered intravenously and
imaging performed. Afterwards EUS-FNA was performed in the same location. Safety
and feasibility were evaluated and CLE structures were registered and correlated
to the standard hematoxylin and eosin cytopathology specimens. Moreover,
additional topical acriflavine-enhanced ex vivo examinations on fresh pancreatic
specimens were conducted. RESULTS: EUS-guided nCLE procedures were accomplished
in all patients. No adverse advents were registered. Furthermore, it was feasible
to do nCLE inside pathological lesions and relatively easy to visualize organ
specific tissue. Despite selecting predefined structures the diagnostic value was
limited mainly due to the missing ability to elucidate the cell nuclei, In the ex
vivo examinations, where acriflavine was administered topically on excised
pancreatic tissue, the nuclei were clearly visualized, thus increasing the
diagnostic value. CONCLUSION: EUS-guided nCLE procedures on focal pancreatic
masses are feasible and safe, but the diagnostic value seems limited. Thus,
further studies using different contrast agents are required to optimize the
diagnostic accuracy.
PMID- 26425526
TI - Gastric cancer-can we rely only on endoscopic ultrasonography?
AB - BACKGROUND: Endoscopic ultrasonography (EUS) is considered to be the most precise
method for locoregional staging, was commonly used for differentiating mucosal
lesions from submucosal lesions. By contrast, computed tomography (CT) was used
to detect the presence of distant metastasis. Both are valuable tools for the pre
operative evaluation of gastric cancer. With the introduction of new therapeutic
options and the recent improvements in CT technology, further evaluation of the
diagnostic accuracy of EUS and multidetector CT (MDCT) is needed. AIM: The
present study was conducted to compare the staging accuracy of EUS with that of
MDCT in series of patients and to evaluate their usefulness in association with
the clinicopathological factors. PATIENTS AND METHODS: In total, 277 patients
with gastric lesions who underwent EUS and CT, hospitalized at Department of
Gastroenterology and Hepatology, Clinical Center, University of Sarajevo. The
results from the pre-operative EUS and MDCT were compared with the post-operative
pathological findings. RESULTS: Among the 277 patients, the overall accuracy of
EUS and MDCT for T staging was 74.7% and 76.9%, respectively. Among the 141
patients with visualized primary lesions on MDCT, the overall accuracy of EUS and
MDCT for T staging was 61.7% and 63.8%, respectively. The overall accuracy for N
staging was 66% and 62.8%, respectively. The performance of EUS and MDCT for
large lesions and lesions at the cardia and angle had significantly lower
accuracy than that of other groups. For EUS, the early gastric cancer lesions
with ulcerative changes had significantly lower accuracy than those without
ulcerative changes. CONCLUSIONS: For the pre-operative assessment of individual T
and N staging in patients with gastric cancer, the accuracy of MDCT was close to
that of EUS. Both EUS and MDCT are useful complementary modalities for the
locoregional staging of gastric cancer.
PMID- 26425527
TI - Utility of endoscopic ultrasonography in the evaluation of dilated common bile
duct of undetermined etiology.
AB - INTRODUCTION: Occasionally, common bile duct (CBD) dilatation is discovered while
working up patients for various causes. Not infrequently, the usual imaging
modalities fail to identify the cause and endoscopic ultrasonography (EUS)
becomes necessary. The aim of this study is to assess the value of EUS in
identifying the cause of CBD dilatation undiagnosed by transabdominal
ultrasonography. PATIENTS AND METHODS: During 1 year, 152 consecutive patients
who were referred for evaluation of dilated CBD (diameter >=7 mm) discovered
incidentally during transabdominal ultrasonography were included. Final diagnoses
were confirmed by endoscopic retrograde cholangiopancreatography, EUS-guided fine
needle aspiration, surgical exploration, or clinical follow-up of at least 10
months. RESULTS: One hundred and fifty two patients (54% female) with dilated CBD
were included. Mean age of patients was 60 +/- 17 years. The final diagnoses was
choledocholithiasis in 32 (21.1%), passed CBD stone in 35 (23%), opium-induced
CBD dilation in 14 (9.2%), post-cholecystectomy states in 20 (13.1%), ampullary
neoplasia in 15 (15.8%), cholangiocarcinoma in 14 (9.2%) and pancreatic head
cancer in 9 (5.9%). Sensitivity, specificity, positive predictive value, negative
predictive value, and accuracy of EUS for patients with abnormal EUS was 89.5%,
100.0%, 100.0%, 91.2%, and 90.9%, respectively. CONCLUSION: After diagnosis of
CBD dilation by transabdominal ultrasonography, EUS may be a reasonable next
choice for determining the etiology of dilated CBD.
PMID- 26425528
TI - Comparison of elastography methods in patients with pancreatic masses.
AB - INTRODUCTION: Endoscopic ultrasonography (EUS) quantitative elastography methods
are developed for non-invasive differentiation of pancreatic masses. AIMS: First:
To evaluate the diagnostic value of strain ratio (SR) and hue histogram (HH) in
patients with pancreatic masses and to determine the cut-off value between
pancreatic cancer and focal pancreatitis using a pancreatic tissue close to the
mass as a reference area. Second: To calculate new variable HH ratio (HHR) in an
attempt to improve sensitivity, specificity and accuracy of the method. METHODS:
In a prospective single center study, 149 patients were examined: 105 with the
pancreatic masses and 44 controls using Pentax EUS linear probes in combination
with Hitachi platforms. SR and HH were automatically calculated by machine
software. Finally, two groups were formed: Pancreatic cancer group (58 patients)
and focal pancreatitis group (47 patients). All statistical analysis has been
made in SPSS 14.0 (SPSS Inc., Chicago, USA). CONCLUSION: Statistical analysis in
our study showed that SR with a cut-off value of 7.59 reaches 100% sensitivity
and 95% specificity with overall accuracy of 97% (confidence intervals [CI]: 92
97%) in detection of pancreatic cancer. Statistical analysis also showed that HH
with a cut-off value of >=86 reaches 100% sensitivity and just 45% specificity
with overall accuracy of 66% (CI: 61-66%) in detection of pancreatic cancer. New
variable HHR with cut-off >=1.153 was slightly better with 98% sensitivity and
50% specificity, with overall accuracy of 69% (CI: 63-70%). SR showed
significantly higher specificity compared with HH and HHR. More HH studies on
Hitachi platforms are needed.
PMID- 26425529
TI - The observation indicator induced from gastrointestinal stromal tumor under long
term monitoring by endoscopic ultrasonography.
AB - INTRODUCTION: We report a case of low-risk stomach gastrointestinal stromal tumor
(GIST) which has been under a long-term observation, obtaining from this
experience knowledge useful in determining the treatment formula for this
disease. RESULTS: During the observation for 6 years, no such change as ulcer
formation was observed in the appearance of the tumor. The measurement of tumor
diameter, however, showed gradual growth of maximum tumor diameter from 2.7 to
5.0 cm. When the changes in the diameter of tumor during this period is plotted,
taking the timeon the horizontal axis and the tumor diameter on the vertical
axis, the growth of the tumor can be approximated with a secondary function,
making it possible to estimate the developmental period of the GIST concerned
from the approximated secondary function. Thus, the developmental period in this
case was estimated to go back 19 years before the time when it was discovered for
the 1(st) time. Further, it was considered that the coefficient of the secondary
function represents the rate of tumor growth, and that comparison with this
coefficient contributed to the evaluation of malignancy stage of the GIST
concerned. CONCLUSION: The growth curve predicting the growth of tumor could be
depicted by measuring the diameter of the tumor in GIST twice or more at an
interval of 6-12 months with EUS, and it was thought that this was utilizable for
determining treatment formula for GISTs.
PMID- 26425530
TI - The analysis of endoscopic ultrasonographic finding for esophageal subepithelial
lesion.
AB - INTRODUCTION: The number of endoscopic ultrasonography (EUS) for esophageal
subepithelial lesion (SEL) is on the increase recently. We retrospectively
investigated the 230 patients who underwent EUS for esophageal SEL from July 2010
to June 2013. We analyzed EUS finding and assumptive diagnosis. RESULTS: Among
230 enrolled patients, subepithelial tumor (SET) was observed in 189 (82.2%)
patients. Mean size of SET was 8.5 +/- 5.0 mm and mean distance from incisor
tooth to lesion was 29.2 +/- 6.7 cm. The most common origin wall layer of the SET
was muscularis mucosa (59.4%), followed by submucosa (15.8%) and muscularis
propria (21.1%). 3.7% of SET was indetermined. In the analysis of primary
assumptive diagnosis, 70.5% was leiomyoma, 16.8% was granular cell tumor, 6.8%
was gastrointestinal stromal tumor, 1.6% was cyst and 2.1% was vascular ectasia.
The tissue sample by biopsy was checked in only 14.2% (27 cases) and the result
was mostly (81.5%) non-specific inflammation. 21 cases (9.1%) of 230 patients
revealed extrinsic compression, 61.9% was compressed by vessel, 33.3% was due to
spine and one case (4.8%) was bronchus. 20 patients (8.7%) was normal without
SEL. 107 patients (46.5%) of enrolled 230 patients repeatedly underwent EUS at
least twice but, 79.4% (85/107) of SET was no change in size or shape.
CONCLUSIONS: Esophageal SEL is mostly benign nature and misdiagnosed as extrinsic
compression or normal variation easily. Thus, meticulous inspection is essential
to distinguish SET and extrinsic compression. EUS is a good modality to examine
esophageal SEL but, EUS is limited to accurate diagnosis of SET. The tissue
acquisition for accurate diagnosis of SET is an important issue.
PMID- 26425531
TI - Evaluation of opium effect on pancreatobiliary system in opium addicted patients
by endoscopic ultrasonography.
AB - INTRODUCTION: Pancreatobiliary abnormalities in patients with opium addiction
have not been widely evaluated by endoscopic ultrasonography before. MATERIALS
AND METHODS: Patients without any pancreatobiliary disease or symptom during 10
months were enrolled in this study. Common bile duct (CBD), pancreatic duct (PD)
and portal vein (PV) diameters, gallbladder wall thickness and surface area of
the papilla and abnormalities were evaluated in both groups by endosonography.
RESULTS: In total, 199 patients were evaluated. 36 (18.1%) cases were addicted to
opium. Mean age of the patients was 56.0 +/- 14.2 years. Opium users had a
statistically significant higher (all P < 0.001) mean diameters of distal CBD
(4.6 +/- 1.9 vs. 3.1 +/- 1.0 mm), middle part of CBD (7.5 +/- 3.1 vs. 4.6 +/- 1.6
mm), PD in head (3.3 +/- 1.3 vs. 2.3 +/- 0.7 mm) and PV (10.3 +/- 2.3 vs. 8.9 +/-
2.1 mm). However, the difference in the diameters of PD in the body of pancreas
and gallbladder wall thickness did not reach statistical significance. The size
of the papilla as measured by the surface area of the papilla of Vater was also
significantly larger in opium users (40.6 +/- 17.1 vs. 29.9 +/- 13.5, P < 0.001).
CONCLUSION: Opium addicted persons have larger diameters of CBD, PV and a larger
surface area of the papilla of Vater. Dilated PD only in the head of the pancreas
might be an important clue to differentiate opium-induced CBD dilation from
periampullary tumors and chronic pancreatitis. The clinical significance of these
findings warrants further investigation.
PMID- 26425532
TI - Role of high resolution ultrasonography/endoscopic ultrasonography and
elastography in predicting lymph node malignancy.
AB - OBJECTIVE: To evaluate the role of high resolution ultrasonography (US) and
endoscopic ultrasonography (EUS)-elastography in predicting malignant
lymphadenopathy. METHODS: This prospective study included 88 patients who
underwent EUS or US examination of different groups of lymph nodes (LNs). The
classification as benign or malignant based on the real-time elastography pattern
and the B-mode US/EUS images was compared to the final diagnosis obtained by EUS
or US guided fine-needle aspiration cytology (FNAC), Tru-Cut biopsy or excisional
biopsy and follow-up in benign lesions not indicated for biopsy for at least 12
months. RESULTS: Regarding the echogenicity, 98.3% of the benign LNs were
hyperechoic, 1.7% were hypoechoic, while 89.7% of the malignant LNs were
hypoechoic, 3.4% were heterogenous and 6.9% were hyperechoic. With cut-off value
of 1.93, the sensitivity of longitudinal to transverse ratio was 73% and the
specificity was 100%. Score 1 elastography had specificity of 100% in diagnosis
of benign LNs, sensitivity was 76.3%, positive predictive value (PPV) was 100%,
negative predictive value (NPV) was 84.7% while Score 2 had a sensitivity of 60%,
specificity of 31.5%, PPV of 15.3%, NPV of 79.3%. Score 3 had a sensitivity of
70.2%, specificity of 100%, PPV of 13.8%, NPV of 100% in detecting malignancy
while Score 4 had a sensitivity of 85.5%, specificity of 100%, PPV of 100%, NPV
of 65.5%. CONCLUSION: Elastography is a promising diagnostic modality that may
complement standard ultrasound and EUS and help guide FNAC during staging of LNs.
PMID- 26425533
TI - Gastric mucosa-associated lymphoid tissue lymphoma associated with pancreatic non
Hodgkin's lymphoma: A case report.
AB - Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal lymphomas that
arise from B lymphocytes located in the marginal zone of lymphoid follicles.
Although, there is a substantial amount of lymphoid tissue in the
gastrointestinal tract, MALT lymphomas usually arise in chronically inflamed
sites that are normally devoid of lymphoid tissue. The best example is gastric
MALT lymphoma that is almost always associated with Helicobacter pylori. Primary
pancreatic lymphoma (PPL) is an extremely rare tumor (1% incidence) and is often
confused with pancreatic adenocarcinoma. By suspecting PPL on clinical and
imaging grounds, surgery and its associated complications can be avoided, since
the mainstay of the treatment is non-surgical strategies including chemotherapy.
We represent a case of a 45-year-old male presented with abdominal pain and
vomiting. Upper endoscopy showed multiple gastric ulcers, biopsies revealed non
specific inflammatory ulcers. The patient was given 4-weeks course of proton pump
inhibitor with no improvement. After few months, he complained of severe
abdominal pain relieved by leaning forward and associated with repeated vomiting.
Upper endoscopy revealed multiple umbilicated gastric masses, 10-20 mm in
diameter. Biopsies were taken, histopathology and immunohistochemistry revealed
MALT lymphoma. Endoscopic ultrasonography was done to the patient and it showed a
pancreatic head mass, fine-needle aspiration was done, histopathology and
immunohistochemistry revealed PPL. The patient received chemotherapy for MALT
lymphoma with near total relief of symptoms and disappearance of gastric and
pancreatic masses. CONCLUSION: This is a rare case having MALT lymphoma
associated with PPL.
PMID- 26425534
TI - A case of gastric aberrant pancreas with bleeding and diagnosed by endoscopic
ultrasonography.
AB - Aberrant pancreas is used to describe ectopic pancreatic tissue lying outside its
normal location with no anatomic or vascular connection to the pancreas proper.
Patients with aberrant pancreas are usually asymptomatic, so aberrant pancreas
are typically discovered incidentally during endoscopy, surgery, or autopsy. This
time, we report a case of gastric aberrant pancreas bleeding was repeated and
endoscopic hemostasis was difficult. A 22-year-old man was admitted to a hospital
with a complaint of epigastric pain and melena. Upper gastrointestinal endoscopy
and endoscopic ultrasonography (EUS) revealed a submucosal tumor with a bleeding
ulcer at the anterior wall of the antrum in the stomach, and diagnosed it as an
aberrant pancreas. It was hard to stop bleeding by in total 7 times endoscopic
hemostasis and anemia was gradually progressed, so partial gastrectomy was
performed. This gastric tumor measured 40 mm * 30 mm * 20 mm and had a severe
ulcerative change. The pathological diagnosis was aberrant pancreas with
Langerhans islet, acinous cells and excretory duct. (Heinrich type) Until
December 2013 in Japan, 13 cases of gastric aberrant pancreas with bleeding have
been reported and in these, a surgery was done in 11 cases. In gastric aberrant
pancreas cases with ulcer formation like this case, endoscopic hemostasis is
expected to be difficult, and surgery is necessary. Hence, early accurate
diagnosis by EUS is a very important to decide better treatment plan.
PMID- 26425536
TI - Dynamic control of pH in esophagus diseases treatment.
AB - During complete medical checkup of proximal gastrointestinal tract, the esophagus
pH measurement is an adventive procedure that requires probes usage, which is
introduced through the endoscope biopsy channel. Such procedure cannot be used
for everyday dynamic treatment control because of its invasiveness. The main aim
of this article is to develop an effective everyday quality control of esophagus
diseases non-traumatic antisecretory treatment. We solve the problem by measuring
the air-ionic esophagus internal environment characteristics with the help of the
air exhaled by the patient analysis. Initial examination is provided during
endoscopic research in the period of patient's planned checkup. Esophagus air
tests are get through biopsy channel and analyzed by computer air-ionic complex.
The range of air-ionic concentration in the esophagus air content is 0.060-0.040
(60-40%) in electrical voltage 0.020-0.050 V, which corresponds to pH 5.0-7.0.
The esophagus air content indexes, received from primary samples are used as
gauging for air-ionic characteristics of air exhausted by patient. Hereafter,
during the therapy course we study only air samples exhausted by the patient on a
daily basis. Air-ionic esophageal pH - measurement is used during checkup and
treatment of 42 patients with gastroesophageal reflux disease diagnose. Parallel
usage of invasive esophageal pH determination method demonstrated complete
results match. Thus, the proposed method is an advanced non-invasive diagnostic
method, which allows to measure intra-esophagus pH indexes and provides probable
assessment of antisecretory drugs treatment efficacy with an ability of
therapeutic course operative correction.
PMID- 26425535
TI - Comparison of capillary versus aspiration technique in endoscopic ultrasound
guided fine-needle aspiration: A preliminary report.
AB - INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is
widely used to diagnose pancreatic malignancies. Different EUS-FNA techniques
have been described to improve sample quality. Recently, a new technique, using
capillarity, has been proposed. AIM: To assess the quality of cytological
samples, comparing two different FNA techniques, in order to optimize tissue
acquisition. METHODS: All consecutive patients with solid pancreatic lesions,
requiring an EUS-FNA, were included in the study between July and September 2013.
All procedures were done under deep sedation. FNA was performed using a 25 gauge
needle, using both capillary and aspiration technique. Patients were randomized
to undergo firstly one or the other technique. Samples were evaluated "on site"
by expert cytotechnologist. An expert cytopathologist, blinded for the technique
used, reviewed the slides, for final diagnosis and assessed sampling quality.
Quality of samples was evaluated through the assessment of the amount of blood,
cellularity, tumoral versus normal cells ratio and adequacy for final diagnosis.
Data were analyzed with Student's t-test and Chi-square test, assuming a
significant P value of 0.05. RESULTS: A total of 30 consecutive patients (19 M,
mean age 67.8 years) with an EUS finding of pancreatic solid lesion were included
in the study. Cytological final diagnosis was adenocarcinoma in 25/30 (83.3%)
cases, neuroendocrine tumor 1/30 (3.3%), intraductal papillary mucosal neoplasms
with high-grade dysplasia 2/30 (6.7%), gastrointestinal stromal tumor in 1/30
(3.3%) and negative for malignant cells 1/30 (3.3%). The difference between the
overall blood amount score per technique was not statistically significant (P =
0.61) as well as the cellularity score (P = 0.08). In 13/30 patients (43%) the
two techniques reported concordant T/N ratio. In 6/30 patients (20%) final
diagnosis was achieved only by capillary obtained smears. In 1/30 patients (3.3%)
the diagnosis was done with aspiration. In the remnant, the ratio between the two
techniques was similar. Adequacy was reached in 24/30 (80%) with aspiration and
29/30 (97%) with capillary technique (P = 0.04). CONCLUSIONS: Aspiration and
capillary sampling techniques provided similar results in cellularity and blood
amount. However, adequacy rate was significantly superior in capillary technique.
Furthermore, in 20% of cases, final diagnosis was achieved only with capillary
samples.
PMID- 26425537
TI - True and false splenic artery aneurysm on endoscopic ultrasonography: Two-case
analysis.
AB - INTRODUCTION: The etiology of true and false splenic artery aneurysm is
different, but the differential X-ray contrast diagnosis could be difficult.
Purpose - to detect endoscopic ultrasonography (EUS) diagnostic capability for
false and true splenic artery aneurysm by considering two clinical cases: With
suspected stomach and pancreatic lesions. MATERIALS AND METHODS: FIRST CASE:
Patient, female, 50-year-old with suspected stomach lesion, complicated by
gastric bleeding. Endoscopy - acute gastric ulcer. X-ray - submucosal gastric
tumor. The patient was sent to the EUS with fine-needle aspiration. SECOND CASE:
Patient, male, 73-year-old with suspected pancreatic neoplasm. Ultrasound -
pancreatic cysts. Computed tomography (CT) - neoplasm of the pancreas body.
Celiacography - splenic artery aneurysm. The patient was sent to the EUS to
clarify the diagnosis. RESULTS: First patient EUS - anechoic rounded lesion with
thick wall close to the stomach. Stomach wall layers were not differentiated
above the lesion. Doppler - turbulent blood flow. EUS excluded submucosal lesion
and proved the presence of aneurysm. CT confirmed the aneurysm. Post-operative
histology - splenic artery pseudoaneurysm, destruction of the stomach wall and
pancreatic parenchyma. Second patient EUS - ovoid solid-cystic lesion with thin
hyperechoic "capsule." Doppler in cystic part - arterial blood flow. EUS
suspected saccular splenic artery aneurysm with the neck and the residual lumen.
Post-operative histology - true splenic artery aneurysm with thrombotic masses
near the wall, pancreatic parenchyma was intact. CONCLUSION: EUS can reliably
differentiate splenic artery aneurysm from gastric submucosal lesion and
differentiate true and false aneurysm with high probability.
PMID- 26425538
TI - Combined endoscopic ultrasonography and endobronchial ultrasound-fine-needle
aspiration for evaluation of mediastinal lymph nodes.
AB - OBJECTIVES: Endoscopic ultrasonography (EUS) and endobronchial ultrasound-fine
needle aspiration (EBUS-FNA), is an accurate technique for evaluation of
mediastinal lymph nodes (MLN) and stadification of lung cancer. The aims of the
study are to evaluate the feasibility and the efficacy of the combined technique
compared with mediastinoscopy for the diagnosis of MLN. DESIGN AND METHODS: All
patients with suspected malignant MLN and/or lung lesion identified by positron
emission tomography-computed tomography underwent combined EUS-EBUS-FNA. The
combined procedure was performed in outpatients under general anesthesia for EUS
and sedation by intravenous midazolam for EBUS when performed separately, using
linear-array echoendoscopes. The MLN were punctured during the EUS and EBUS-FNA
procedures with a 22 gauge needle. RESULTS: Thirty-four patients underwent
consecutively EUS and EBUS-FNA between September 2011 and November 2013 (8 women,
26 men, mean age of 65.9 year, range: 51-83). Combined EUS-EBUS-FNA was performed
in a single time procedure in 26 patients (mean time 50 min) and in two different
times in eight patients (mean delay 3 days). Twenty-five malignant and 9
inflammatory lesions were diagnosed. Mediastinoscopy was performed in nine
patients and confirmed in eight patients the initial combined EUS-EBUS-FNA
diagnosis. The diagnosis was obtained in 91.2% with EUS-FNA, 70.6% with EBUS-FNA
and 97% when combined procedure was performed. The overall sensitivity,
specificity, positive and negative predictive values of EUS-EBUS-FNA for
diagnosing malignancy were 96.5%, 100%, 100% and 90% respectively. No
complications related to the procedure were observed. CONCLUSION: Combined EUS
EBUS-FNA represents an accurate technique in the diagnosis of MLN, can be done in
a single time procedure and has the advantage of being less invasive than
mediastinoscopy.
PMID- 26425539
TI - Endoscopic ultrasonography for intra-abdominal textiloma.
AB - INTRODUCTION: The term textiloma is used to describe foreign body (swab)
forgotten during surgery. We don't know any case of the description of endoscopic
ultrasonography (EUS) for intra-abdominal textiloma. OBJECTIVES: To determine the
EUS capabilities in the topical diagnosis of intra-abdominal textiloma. MATERIALS
AND METHODS: Patient, female, 57-year-old was admitted to our hospital with post
operative hernia. 10 months before the patient underwent surgery (laparotomy,
splenectomy) in another hospital. For ethical reasons, we do not name that
hospital. Intra-abdominal lesion has been accidentally revealed by computed
tomography during the pre-operative examination prior to hernioplasty. Ultrasound
unclear detected hyperechoic lesion with a dense acoustic shadow. The patient was
sent to the EUS to clarify the diagnosis and to determine the topography of the
lesion, fine-needle aspiration - if required. RESULTS: EUS revealed a hyperechoic
corrugated border of the lesion with a dense acoustic shadow - between the
gastric wall and the lower surface of the liver. Taking into account preceding
surgery EUS suspected textiloma. The patient underwent hernioplasty and revision
of the abdominal cavity. Textiloma has been revealed between the stomach and
liver. CONCLUSION: EUS correctly diagnosed textiloma and accurately determined
its location.
PMID- 26425540
TI - Do Panic Symptoms Affect the Quality of Life and Add to the Disability in
Patients with Bronchial Asthma?
AB - Background. Anxiety and panic are known to be associated with bronchial asthma
with variety of impact on clinical presentation, treatment outcome,
comorbidities, quality of life, and functional disability in patients with
asthma. This study aims to explore the pattern of panic symptoms, prevalence and
severity of panic disorder (PD), quality of life, and disability in them.
Methods. Sixty consecutive patients of bronchial asthma were interviewed using
semistructured proforma, Panic and Agoraphobia scale, WHO Quality of life (QOL)
BREF scale, and WHO disability schedule II (WHODAS II). Results. Though 60% of
the participants had panic symptoms, only 46.7% had diagnosable panic attacks
according to DSM IV TR diagnostic criteria and 33.3% had PD. Most common symptoms
were "sensations of shortness of breath or smothering," "feeling of choking," and
"fear of dying" found in 83.3% of the participants. 73.3% of the participants had
poor quality of life which was most impaired in physical and environmental
domains. 55% of the participants had disability score more than a mean (18.1).
Conclusion. One-third of the participants had panic disorder with significant
effect on physical and environmental domains of quality of life. Patients with
more severe PD and bronchial asthma had more disability.
PMID- 26425541
TI - Prevalence and Factors Associated with Perceived Stigma among Patients with
Epilepsy in Ethiopia.
AB - Background. Epilepsy stigma is considered to be one of the most important factors
that have a negative influence on people with epilepsy. Among all types of stigma
perceived stigma further exerts stress and restricts normal participation in
society. Methods. Hospital based cross-sectional study was conducted from May 1,
2013, to May 30, 2013. All patients with epilepsy in Ethiopia were source
population. The sample size was determined using single population proportion
formula and 347 subjects were selected by using systematic random sampling
method. Data was analyzed by using SPSS version 20. Results. A total of 346
participants with mean age of 29.3 +/- 8.5 SD participated with a response rate
of 99.7%. The prevalence of perceived stigma was 31.2%. Age range between 18 and
24 [AOR = 2.84, 95%CI: 1.02, 7.92], difficulty to attend follow-up because of
stigma [AOR = 3.15, 95%CI: 1.19, 8.34], seizure related injury [AOR = 1.88,
95%CI: 1.12, 3.15], and contagion belief [AOR = 1.88, 95%CI: 1.10, 5.08] were
significantly associated with perceived stigma. Conclusions. Perceived stigma was
found to be a common problem among patients suffering from epilepsy. The results
reinforce the need for creating awareness among patients with epilepsy and
addressing misconceptions attached to epilepsy.
PMID- 26425542
TI - The Contribution of Alexithymia to Obsessive-Compulsive Disorder Symptoms
Dimensions: An Investigation in a Large Community Sample in Italy.
AB - Poor attention has been dedicated to the relation between Alexithymia and
specific OCD symptoms dimensions. Knowledge about which Alexithymia domains are
the most affected ones in OCD dimensions could inform clinical practice,
suggesting the need for the introduction of psychotherapeutic interventions
targeting Alexithymia deficits. The current study aimed to investigate which OCD
symptom dimension correlated with Alexithymia domains. A total of 425 community
individuals (mean age = 27.80, SD = 9.89, 60% women) completed measures of
Alexithymia, OCD symptoms dimensions, anxiety, and depression. Moderate
correlations emerged between Difficulty Identifying Feelings and Hoarding (r =
.36, p < .001) and Checking symptoms (r = .34, p < .001) and between Difficulty
Describing Feelings and Pure Obsessing (r = .31, p < .001). Difficulty
Identifying Feelings uniquely predicted OCD symptoms (beta = 0.20, t = 3.96, and
p < .001), after controlling for anxiety and depression. A main effect emerged of
Alexithymia on Ordering (beta = 0.70, t = 2.50, p < .05) and Pure Obsessing
symptoms (beta = 0.043, t = 2.08, and p < .05). Psychotherapeutic interventions
specifically targeting Alexithymia should be integrated in the treatment of
Ordering and Pure Obsessing symptoms. Difficulty Identifying Feelings and
Difficulty Describing Feelings should be addressed in the psychotherapeutic
treatment of Hoarding, Checking, and Pure Obsessing, respectively.
PMID- 26425543
TI - Exploring the Functional Disorder and Corresponding Key Transcription Factors in
Intraductal Papillary Mucinous Neoplasms Progression.
AB - This study has analyzed the gene expression patterns of an IPMN microarray
dataset including normal pancreatic ductal tissue (NT), intraductal papillary
mucinous adenoma (IPMA), intraductal papillary mucinous carcinoma (IPMC), and
invasive ductal carcinoma (IDC) samples. And eight clusters of differentially
expressed genes (DEGs) with similar expression pattern were detected by k-means
clustering. Then a survey map of functional disorder in IPMN progression was
established by functional enrichment analysis of these clusters. In addition,
transcription factors (TFs) enrichment analysis was used to detect the key TFs in
each cluster of DEGs, and three TFs (FLI1, ERG, and ESR1) were found to
significantly regulate DEGs in cluster 1, and expression of these three TFs was
validated by qRT-PCR. All these results indicated that these three TFs might play
key roles in the early stages of IPMN progression.
PMID- 26425546
TI - Comment on "Maternal Satisfaction on Delivery Service and Its Associated Factors
among Mothers Who Gave Birth in Public Health Facilities of Debre Markos Town,
Northwest Ethiopia".
PMID- 26425545
TI - Yeast Actin-Related Protein ARP6 Negatively Regulates Agrobacterium-Mediated
Transformation of Yeast Cell.
AB - The yeasts, including Saccharomyces cerevisiae and Pichia pastoris, are single
cell eukaryotic organisms that can serve as models for human genetic diseases and
hosts for large scale production of recombinant proteins in current
biopharmaceutical industry. Thus, efficient genetic engineering tools for yeasts
are of great research and economic values. Agrobacterium tumefaciens-mediated
transformation (AMT) can transfer T-DNA into yeast cells as a method for genetic
engineering. However, how the T-DNA is transferred into the yeast cells is not
well established yet. Here our genetic screening of yeast knockout mutants
identified a yeast actin-related protein ARP6 as a negative regulator of AMT.
ARP6 is a critical member of the SWR1 chromatin remodeling complex (SWR-C);
knocking out some other components of the complex also increased the
transformation efficiency, suggesting that ARP6 might regulate AMT via SWR-C.
Moreover, knockout of ARP6 led to disruption of microtubule integrity, higher
uptake and degradation of virulence proteins, and increased DNA stability inside
the cells, all of which resulted in enhanced transformation efficiency. Our
findings have identified molecular and cellular mechanisms regulating AMT and a
potential target for enhancing the transformation efficiency in yeast cells.
PMID- 26425547
TI - Chemotherapy-Induced Nausea and Vomiting.
PMID- 26425544
TI - Targeted Therapies in Adult B-Cell Malignancies.
AB - B-lymphocytes are programmed for the production of immunoglobulin (Ig) after
antigen presentation, in the context of T-lymphocyte control within lymphoid
organs. During this differentiation/activation process, B-lymphocytes exhibit
different restricted or common surface markers, activation of cellular pathways
that regulate cell cycle, metabolism, proteasome activity, and protein synthesis.
All molecules involved in these different cellular mechanisms are potent
therapeutic targets. Nowadays, due to the progress of the biology, more and more
targeted drugs are identified, a situation that is correlated with an extended
field of the targeted therapy. The full knowledge of the cellular machinery and
cell-cell communication allows making the best choice to treat patients, in the
context of personalized medicine. Also, focus should not be restricted to the
immediate effects observed as clinical endpoints, that is, response rate,
survival markers with conventional statistical methods, but it should consider
the prediction of different clinical consequences due to other collateral drug
targets, based on new methodologies. This means that new reflection and new
bioclinical follow-up have to be monitored, particularly with the new drugs used
with success in B-cell malignancies. This review discussed the principal aspects
of such evident bioclinical progress.
PMID- 26425548
TI - Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate
Vaccines for Follicular Lymphoma.
AB - We report the first evaluation of plant-made conjugate vaccines for targeted
treatment of B-cell follicular lymphoma (FL) in a Phase I safety and
immunogenicity clinical study. Each recombinant personalized immunogen consisted
of a tumor-derived, plant-produced idiotypic antibody (Ab) hybrid comprising the
hypervariable regions of the tumor-associated light and heavy Ab chains,
genetically grafted onto a common human IgG1 scaffold. Each immunogen was
produced in Nicotiana benthamiana plants using twin magnICON vectors expressing
the light and heavy chains of the idiotypic Ab. Each purified Ab was chemically
linked to the carrier protein keyhole limpet hemocyanin (KLH) to form a conjugate
vaccine. The vaccines were administered to FL patients over a series of >=6
subcutaneous injections in conjunction with the adjuvant Leukine (GM-CSF). The 27
patients enrolled in the study had previously received non-anti-CD20
cytoreductive therapy followed by >=4 months of immune recovery prior to first
vaccination. Of 11 patients who became evaluable at study conclusion, 82% (9/11)
displayed a vaccine-induced, idiotype-specific cellular and/or humoral immune
response. No patients showed serious adverse events (SAE) related to vaccination.
The fully scalable plant-based manufacturing process yields safe and immunogenic
personalized FL vaccines that can be produced within weeks of obtaining patient
biopsies.
PMID- 26425549
TI - The Implications of HIV Treatment on the HIV-Malaria Coinfection Dynamics: A
Modeling Perspective.
AB - Most hosts harbor multiple pathogens at the same time in disease epidemiology.
Multiple pathogens have the potential for interaction resulting in negative
impacts on host fitness or alterations in pathogen transmission dynamics. In this
paper we develop a mathematical model describing the dynamics of HIV-malaria
coinfection. Additionally, we extended our model to examine the role treatment
(of malaria and HIV) plays in altering populations' dynamics. Our model consists
of 13 interlinked equations which allow us to explore multiple aspects of HIV
malaria transmission and treatment. We perform qualitative analysis of the model
that includes positivity and boundedness of solutions. Furthermore, we evaluate
the reproductive numbers corresponding to the submodels and investigate the long
term behavior of the submodels. We also consider the qualitative dynamics of the
full model. Sensitivity analysis is done to determine the impact of some chosen
parameters on the dynamics of malaria. Finally, numerical simulations illustrate
the potential impact of the treatment scenarios and confirm our analytical
results.
PMID- 26425551
TI - Expression of Translationally Controlled Tumor Protein in Human Kidney and in
Renal Cell Carcinoma.
AB - Translationally controlled tumor protein is a multifaceted protein involved in
several physiological and biological functions. Its expression in normal kidney
and in renal carcinomas, once corroborated by functional data, may add elements
to elucidate renal physiology and carcinogenesis. In this study, translationally
controlled tumor protein expression was evaluated by quantitative real time
polymerase chain reaction and western blotting, and its localization was examined
by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein
expression was found in the cytoplasm of proximal and distal tubular cells, in
cells of the thick segment of the loop of Henle, and in urothelial cells of the
pelvis. It was also detectable in cells of renal carcinoma with different pattern
of localization (membranous and cytoplasmic) depending on tumor histotype. Our
data may suggest an involvement of translationally controlled tumor protein in
normal physiology and carcinogenesis. However, functional in vitro and in vivo
studies are needed to verify this hypothesis.
PMID- 26425550
TI - Reviving Lonidamine and 6-Diazo-5-oxo-L-norleucine to Be Used in Combination for
Metabolic Cancer Therapy.
AB - Abnormal metabolism is another cancer hallmark. The two most characterized
altered metabolic pathways are high rates of glycolysis and glutaminolysis, which
are natural targets for cancer therapy. Currently, a number of newer compounds to
block glycolysis and glutaminolysis are being developed; nevertheless, lonidamine
and 6-diazo-5-oxo-L-norleucine (DON) are two old drugs well characterized as
inhibitors of glycolysis and glutaminolysis, respectively, whose clinical
development was abandoned years ago when the importance of cancer metabolism was
not fully appreciated and clinical trial methodology was less developed. In this
review, a PubMed search using the words lonidamine and 6-diazo-5-oxo-L-norleucine
(DON) was undertaken to analyse existing information on the preclinical and
clinical studies of these drugs for cancer treatment. Data show that they exhibit
antitumor effects; besides there is also the suggestion that they are
synergistic. We conclude that lonidamine and DON are safe and potentially
effective drugs that need to be reevaluated in combination as metabolic therapy
of cancer.
PMID- 26425552
TI - A Bayesian Outbreak Detection Method for Influenza-Like Illness.
AB - Epidemic outbreak detection is an important problem in public health and the
development of reliable methods for outbreak detection remains an active research
area. In this paper we introduce a Bayesian method to detect outbreaks of
influenza-like illness from surveillance data. The rationale is that, during the
early phase of the outbreak, surveillance data changes from autoregressive
dynamics to a regime of exponential growth. Our method uses Bayesian model
selection and Bayesian regression to identify the breakpoint. No free parameters
need to be tuned. However, historical information regarding influenza-like
illnesses needs to be incorporated into the model. In order to show and discuss
the performance of our method we analyze synthetic, seasonal, and pandemic
outbreak data.
PMID- 26425553
TI - Understanding Transcription Factor Regulation by Integrating Gene Expression and
DNase I Hypersensitive Sites.
AB - Transcription factors are proteins that bind to DNA sequences to regulate gene
transcription. The transcription factor binding sites are short DNA sequences (5
20 bp long) specifically bound by one or more transcription factors. The
identification of transcription factor binding sites and prediction of their
function continue to be challenging problems in computational biology. In this
study, by integrating the DNase I hypersensitive sites with known position weight
matrices in the TRANSFAC database, the transcription factor binding sites in gene
regulatory region are identified. Based on the global gene expression patterns in
cervical cancer HeLaS3 cell and HelaS3-ifnalpha4h cell (interferon treatment on
HeLaS3 cell for 4 hours), we present a model-based computational approach to
predict a set of transcription factors that potentially cause such differential
gene expression. Significantly, 6 out 10 predicted functional factors, including
IRF, IRF-2, IRF-9, IRF-1 and IRF-3, ICSBP, belong to interferon regulatory factor
family and upregulate the gene expression levels responding to the interferon
treatment. Another factor, ISGF-3, is also a transcriptional activator induced by
interferon alpha. Using the different transcription factor binding sites selected
criteria, the prediction result of our model is consistent. Our model
demonstrated the potential to computationally identify the functional
transcription factors in gene regulation.
PMID- 26425554
TI - iTRAQ-Based Quantitative Proteomic Analysis Identified HSC71 as a Novel Serum
Biomarker for Renal Cell Carcinoma.
AB - Renal cell carcinoma (RCC) is one of the most lethal urologic cancers and about
80% of RCC are of the clear-cell type (ccRCC). However, there are no serum
biomarkers for the accurate diagnosis of RCC. In this study, we performed a
quantitative proteomic analysis on serum samples from ccRCC patients and control
group by using isobaric tag for relative and absolute quantitation (iTRAQ)
labeling and LC-MS/MS analysis to access differentially expressed proteins.
Overall, 16 proteins were significantly upregulated (ratio > 1.5) and 14 proteins
were significantly downregulated (ratio < 0.67) in early-stage ccRCC compared to
control group. HSC71 was selected and subsequently validated by Western blot in
six independent sets of patients. ELISA subsequently confirmed HSC71 as a
potential serum biomarker for distinguishing RCC from benign urologic disease
with an operating characteristic curve (ROC) area under the curve (AUC) of 0.86
(95% confidence interval (CI), 0.76~0.96), achieving sensitivity of 87% (95% CI
69%~96%) at a specificity of 80% (95% CI 61~92%) with a threshold of 15 ng/mL.
iTRAQ-based quantitative proteomic analysis led to identification of serum HSC71
as a novel serum biomarker of RCC, particularly useful in early diagnosis of
ccRCC.
PMID- 26425555
TI - Association of Tag SNPs and Rare CNVs of the MIR155HG/miR-155 Gene with Epilepsy
in the Chinese Han Population.
AB - BACKGROUND: miR-155 likely acts as an important modulator in the inflammatory
mechanism of epilepsy, and this study investigated its association with epilepsy
from the perspective of molecular genetics. METHODS: This study enrolled 249
epileptic patients and 289 healthy individuals of the Chinese Han population; 4
tag single-nucleotide polymorphisms (SNPs: rs969885, rs12483428, rs987195, and
rs4817027) of the MIR155HG/miR-155 gene were selected, and their association with
epilepsy was investigated. Additionally, this study determined the copy numbers
of the MIR155HG/miR-155 gene. RESULTS: The TCA haplotype (rs12483428-rs987195
rs4817027) and the AA genotype at rs4817027 conferred higher vulnerability to
epilepsy in males. Stratification by age of onset revealed that the CC haplotype
(rs969885-rs987195) was a genetic susceptibility factor for early-onset epilepsy.
Further stratification by drug-resistant status indicated the CC haplotype
(rs969885-rs987195) and the AA genotype at rs4817027 were genetic susceptibility
factors for drug-resistant epilepsy (DRE) but the CG haplotype (rs987195
rs969885) was a genetically protective factor against DRE. Besides, 3 epileptic
patients with copy number variants of the MIR155HG/miR-155 gene were observed.
CONCLUSIONS: This study first demonstrates the association of MIR155HG/miR-155
tag SNPs with epilepsy and shows that rare CNVs were found exclusively in
epileptic patients, clarifying the genetic role of miR-155 in epilepsy.
PMID- 26425557
TI - Prophylactic Management of Radiation-Induced Nausea and Vomiting.
AB - The incidence of nausea and vomiting after radiotherapy is often underestimated
by physicians, though some 50-80% of patients may experience these symptoms. The
occurrence of radiotherapy-induced nausea and vomiting (RINV) will depend on
radiotherapy-related factors, such as the site of irradiation, the dosing,
fractionation, irradiated volume, and radiotherapy techniques. Patients should
receive antiemetic prophylaxis as suggested by the international antiemetic
guidelines based upon a risk assessment, taking especially into account the
affected anatomic region and the planned radiotherapy regimen. In this field the
international guidelines from the Multinational Association of Supportive Care in
Cancer (MASCC)/European Society of Medical Oncology (ESMO) and the American
Society of Clinical Oncology (ASCO) guidelines as well as the National
Comprehensive Cancer Network (NCCN) are widely endorsed. The emetogenicity of
radiotherapy regimens and recommendations for the appropriate use of antiemetics
including 5-hydroxytryptamine (5-HT3) receptor antagonists, steroids, and other
antiemetics will be reviewed in regard to the applied radiotherapy or
radiochemotherapy regimen.
PMID- 26425556
TI - MicroRNA Promoter Identification in Arabidopsis Using Multiple Histone Markers.
AB - A microRNA is a small noncoding RNA molecule, which functions in RNA silencing
and posttranscriptional regulation of gene expression. To understand the
mechanism of the activation of microRNA genes, the location of promoter regions
driving their expression is required to be annotated precisely. Only a fraction
of microRNA genes have confirmed transcription start sites (TSSs), which hinders
our understanding of the transcription factor binding events. With the
development of the next generation sequencing technology, the chromatin states
can be inferred precisely by virtue of a combination of specific histone
modifications. Using the genome-wide profiles of nine histone markers including
H3K4me2, H3K4me3, H3K9Ac, H3K9me2, H3K18Ac, H3K27me1, H3K27me3, H3K36me2, and
H3K36me3, we developed a computational strategy to identify the promoter regions
of most microRNA genes in Arabidopsis, based upon the assumption that the
distribution of histone markers around the TSSs of microRNA genes is similar to
the TSSs of protein coding genes. Among 298 miRNA genes, our model identified 42
independent miRNA TSSs and 132 miRNA TSSs, which are located in the promoters of
upstream genes. The identification of promoters will provide better understanding
of microRNA regulation and can play an important role in the study of diseases at
genetic level.
PMID- 26425558
TI - Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa.
AB - Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and
among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic
immunotherapy with anti-CD20 monoclonal antibody has been investigated as first
line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas
is still unknown. The present study evaluated retrospectively the outcome of
seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom
six were treated with single agent Rituximab. All patients received 6 cycles of
Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was
100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a
partial response. In four patients an additional Rituximab maintenance every 2-3
months was given for two years. After a median follow-up of 29 months (range 8
34), no recurrences were observed, without of therapy- or disease-related severe
adverse events. None of the patients needed additional radiotherapy or other
treatments. Rituximab as a single agent is highly effective and tolerable in
first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore,
durable responses are achievable with the same-agent maintenance. Rituximab can
be considered the agent of choice in the management of an indolent disease in
whom the "quality of life" matter is of primary importance.
PMID- 26425559
TI - Orthostatic Intolerance Is Independent of the Degree of Autonomic Cardiovascular
Adaptation after 60 Days of Head-Down Bed Rest.
AB - Spaceflight and head-down bed rest (HDBR) can induce the orthostatic intolerance
(OI); the mechanisms remain to be clarified. The aim of this study was to
determine whether or not OI after HDBR relates to the degree of autonomic
cardiovascular adaptation. Fourteen volunteers were enrolled for 60 days of HDBR.
A head-up tilt test (HUTT) was performed before and after HDBR. Our data revealed
that, in all nonfainters, there was a progressive increase in heart rate over the
course of HDBR, which remained higher until 12 days of recovery. The mean
arterial pressure gradually increased until day 56 of HDBR and returned to
baseline after 12 days of recovery. Respiratory sinus arrhythmia and baroreflex
sensitivity decreased during HDBR and remained suppressed until 12 days of
recovery. Low-frequency power of systolic arterial pressure increased during HDBR
and remained elevated during recovery. Three subjects fainted during the HUTT
after HDBR, in which systemic vascular resistance did not increase and remained
lower until syncope. None of the circulatory patterns significantly differed
between the fainters and the nonfainters at any time point. In conclusion, our
data indicate that the impaired orthostatic tolerance after HDBR could not be
distinguished by estimation of normal hemodynamic and/or neurocardiac data.
PMID- 26425560
TI - The Roles of Hedgehog Signaling in Upper Lip Formation.
AB - Craniofacial development consists of a highly complex sequence of the
orchestrated growth and fusion of facial processes. It is also known that
craniofacial abnormalities can be detected in 1/3 of all patients with congenital
diseases. Within the various craniofacial abnormalities, orofacial clefting is
one of the most common phenotypic outcomes associated with retarded facial growth
or fusion. Cleft lip is one of the representative and frequently encountered
conditions in the spectrum of orofacial clefting. Despite various mechanisms or
signaling pathways that have been proposed to be the cause of cleft lip, a
detailed mechanism that bridges individual signaling pathways to the cleft lip is
still elusive. Shh signaling is indispensable for normal embryonic development,
and disruption can result in a wide spectrum of craniofacial disorders, including
cleft lip. This review focuses on the current knowledge about the mechanisms of
facial development and the etiology of cleft lip that are related to Shh
signaling.
PMID- 26425561
TI - Subcutaneous Administration of Bortezomib in Combination with Thalidomide and
Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients.
AB - OBJECTIVE: To investigate the efficacy and safety of the treatment of the newly
diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ)
administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.
METHODS: A total of 60 newly diagnosed MM patients were analyzed. 30 patients
received improved VTD regimen (improved VTD group) with the subQ injection of
bortezomib and the other 30 patients received conventional VTD regimen (VTD
group).The efficacy and safety of two groups were analyzed retrospectively.
RESULTS: The overall remission (OR) after eight cycles of treatment was 73.3% in
the VTD group and 76.7% in the improved VTD group (P > 0.05). No significant
differences in time to 1-year estimate of overall survival (72% versus 75%, P =
0.848) and progression-free survival (median 22 months versus 25 months; P =
0.725) between two groups. The main toxicities related to therapy were
leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and
urinary disorders. Grade 3 and higher adverse events were significantly less
common in the improved VTD group (50%) than VTD group (80%, P = 0.015).
CONCLUSIONS: The improved VTD regimen by changing bortezomib from intravenous
administration to subcutaneous injection has noninferior efficacy to standard VTD
regimen, with an improved safety profile and reduced adverse events.
PMID- 26425562
TI - Impact of CYP1A1 Polymorphisms on Susceptibility to Chronic Obstructive Pulmonary
Disease: A Meta-Analysis.
AB - OBJECTIVE: Several studies have evaluated the association between CYP1A1
polymorphisms and the susceptibility of chronic obstructive pulmonary disease
(COPD) with inconclusive results. We performed the first comprehensive meta
analysis to summarize the association between CYP1A1 polymorphisms and COPD risk.
METHOD: A systematic literature search was conducted (up to April 2015) in five
online databases: PubMed, EMBASE, China National Knowledge Infrastructure (CNKI),
WeiPu, and WanFang databases. The strength of association was calculated by odds
ratio (OR) and corresponding 95% confidence interval (CI). RESULTS: Seven case
control studies with 1050 cases and 1202 controls were included. Our study
suggested a significant association between the MspI polymorphism and COPD risk
(CC versus TC + TT: OR = 1.57, CI: 1.09-2.26, P = 0.02; CC versus TT: OR = 1.73,
CI: 1.18-2.55, P = 0.005). For the Ile/Val polymorphism, a significant
association with COPD risk was observed (GG versus AG + AA: OR = 2.75, CI: 1.29
5.84, P = 0.009; GG versus AA: OR = 3.23, CI: 1.50-6.93, P = 0.003; AG versus AA:
OR = 1.39, CI: 1.01-1.90, P = 0.04). Subgroup analysis indicated a significant
association between the MspI variation and COPD risk among Asians (CC versus TC +
TT: OR = 1.70, CI: 1.06-2.71, P = 0.03; CC versus TT: OR = 1.84, CI: 1.11-3.06, P
= 0.02). CONCLUSION: The MspI and Ile/Val polymorphisms might alter the
susceptibility of COPD, and MspI polymorphism might play a role in COPD risk
among Asian population.
PMID- 26425563
TI - Management of Chemotherapy Induced Nausea and Vomiting in Patients on Multiday
Cisplatin Based Combination Chemotherapy.
AB - Introduction of cisplatin based chemotherapy has revolutionized the treatment of
germ cell tumors. A common side effect of multiday cisplatin chemotherapy is
severe nausea and vomiting. Considerable progress has been made in the control of
these side effects since the introduction of cisplatin based chemotherapy in the
1970s. Germ cell tumor which is a model for a curable neoplasm has also turned
into an excellent testing ground to develop effective strategies to prevent
chemotherapy induced nausea and vomiting (CINV) in multiday cisplatin based
regimens. The use of combination of a 5-hydroxytryptamine (HT)3 receptor
antagonist, a neurokinin-1 (NK1) antagonist, and dexamethasone has greatly
improved our ability to prevent and control acute and delayed CINV. Mechanism and
pattern of CINV with multiday chemotherapy may differ from those in single day
chemotherapy and therefore efficacy of antiemetic drugs as observed in single day
chemotherapy may not be applicable. There are only few randomized clinical trials
with special emphasis on multiday chemotherapy. Further studies are essential to
determine the efficacy, optimal dose, and duration of the newer agents and
combinations in multiday cisplatin based chemotherapy.
PMID- 26425564
TI - Efficacy of Olanzapine Combined Therapy for Patients Receiving Highly Emetogenic
Chemotherapy Resistant to Standard Antiemetic Therapy.
AB - OBJECTIVE: Olanzapine is proved to be effective for chemotherapy induced nausea
and vomiting (CINV). But its efficacy in combination with standard antiemetic
therapy is unknown. The purpose of this study is to prove the preventive effect
of olanzapine for the prevention of CINV caused by highly emetogenic chemotherapy
when used with standard antiemetic therapy. METHOD: Gynecologic cancer patients
receiving cisplatin-based chemotherapy who had grade 2 or 3 nausea in overall
phase (0-120 h after chemotherapy) despite standard therapy were assigned to this
study. From the next cycles to cycles in which patients developed grade 2 or 3
nausea, they received olanzapine with standard therapy. 5 mg oral olanzapine was
administered for 7 days from the day before chemotherapy. The effectiveness of
preventive administration of olanzapine was evaluated retrospectively. The
primary endpoint was nausea control rate (grade 0 or 1) with olanzapine. RESULTS:
Fifty patients were evaluable. The nausea control rate with olanzapine was
improved from 58% to 98% in acute phase (0-24 h after chemotherapy) and 2% to 94%
in delayed phase (24-120 h after chemotherapy). In overall phase, the nausea
control rate improved from 0% to 92%, and it was statistically significant (P <
0.001). CONCLUSION: Preventive use of olanzapine combined with standard
antiemetic therapy showed improvement in control of refractory nausea.
PMID- 26425565
TI - Following Up Crack Users after Hospital Discharge Using Record Linkage
Methodology: An Alternative to Find Hidden Populations.
AB - This paper presents the probabilistic record linkage (PRL) methodology as an
alternative way to find or follow up hard-to-reach population as crack users. PRL
was based on secondary data from public health information systems and the
strategy used from standardization; phonetic encoding and the rounds of matching
data were described. A total of 293 patient records from medical database and two
administrative datasets obtained from Ministry of Health Information Systems were
used. Patient information from the medical database was the identifiers to the
administrative datasets containing data on outpatient treatment and hospital
admissions. 40% of patient records were found in the hospital database and 12%
were found in the outpatient database; 95% of the patients were hospitalized up
to 5 times, and only 10 out of them had outpatient information. The record
linkage methodology by linking government databases may help to address research
questions about the path of patients in the care network without spending time
and financial resources with primary data collection.
PMID- 26425567
TI - Prevalence, Clinical Correlates, and Use of Glucose-Lowering Drugs among Older
Patients with Type 2 Diabetes Living in Long-Term Care Facilities.
AB - Prevalence, clinical correlates, and use of glucose-lowering drugs were
comprehensively evaluated among 863 nursing home older patients with diabetes
(mean age 82.9 +/- 2.1 years): functional dependence and cognitive impairment
were present in 84.1% and 68% of patients, respectively, and 66.3% of patients
had 2-4 comorbidities. HbA1c values < 7.0% were documented in 54.9% of diabetic;
significantly lower HbA1c levels were observed in demented patients than in
nondemented subjects. Documented hypoglycemic episodes were reported for 57
patients (6.6%), without significant association with age, functional dependence,
cognitive impairment, or HbA1c levels. About one-fifth of older long-term
facilities residents have diabetes, with concomitant poor health conditions and
high prevalence of cognitive impairment and functional dependence. Roughly three
fourths of these older and frail diabetic patients have HbA1c values lower than
optimal, suggesting a potential for hypoglycemic harm especially among patients
with severe cognitive impairment.
PMID- 26425566
TI - Active Microbial Communities Inhabit Sulphate-Methane Interphase in Deep Bedrock
Fracture Fluids in Olkiluoto, Finland.
AB - Active microbial communities of deep crystalline bedrock fracture water were
investigated from seven different boreholes in Olkiluoto (Western Finland) using
bacterial and archaeal 16S rRNA, dsrB, and mcrA gene transcript targeted 454
pyrosequencing. Over a depth range of 296-798 m below ground surface the
microbial communities changed according to depth, salinity gradient, and sulphate
and methane concentrations. The highest bacterial diversity was observed in the
sulphate-methane mixing zone (SMMZ) at 250-350 m depth, whereas archaeal
diversity was highest in the lowest boundaries of the SMMZ. Sulphide-oxidizing
epsilon-proteobacteria (Sulfurimonas sp.) dominated in the SMMZ and gamma
proteobacteria (Pseudomonas spp.) below the SMMZ. The active archaeal communities
consisted mostly of ANME-2D and Thermoplasmatales groups, although
Methermicoccaceae, Methanobacteriaceae, and Thermoplasmatales (SAGMEG, TMG) were
more common at 415-559 m depth. Typical indicator microorganisms for sulphate
methane transition zones in marine sediments, such as ANME-1 archaea, alpha-,
beta- and delta-proteobacteria, JS1, Actinomycetes, Planctomycetes, Chloroflexi,
and MBGB Crenarchaeota were detected at specific depths. DsrB genes were most
numerous and most actively transcribed in the SMMZ while the mcrA gene
concentration was highest in the deep methane rich groundwater. Our results
demonstrate that active and highly diverse but sparse and stratified microbial
communities inhabit the Fennoscandian deep bedrock ecosystems.
PMID- 26425568
TI - Metastatic Insulinoma Following Resection of Nonsecreting Pancreatic Islet Cell
Tumor: A Case Report and Review of the Literature.
AB - A 56-year-old woman presented to our clinic for recurrent hypoglycemia after
undergoing resection of an incidentally discovered nonfunctional pancreatic
endocrine tumor 6 years ago. She underwent a distal pancreatectomy and
splenectomy, after which she developed diabetes and was placed on an insulin
pump. Pathology showed a pancreatic endocrine neoplasm with negative islet
hormone immunostains. Two years later, computed tomography scan of the abdomen
showed multiple liver lesions. Biopsy of a liver lesion showed a well
differentiated neuroendocrine neoplasm, consistent with pancreatic origin. Six
years later, she presented to clinic with 1.5 years of recurrent hypoglycemia.
Laboratory results showed elevated proinsulin, insulin levels, and c-peptide
levels during a hypoglycemic episode. Computed tomography scan of the abdomen
redemonstrated multiple liver lesions. Repeated transarterial catheter
chemoembolization and microwave thermal ablation controlled hypoglycemia. The
unusual features of interest of this case include the transformation of
nonfunctioning pancreatic endocrine tumor to a metastatic insulinoma and the
occurrence of atrial flutter after octreotide for treatment.
PMID- 26425569
TI - Obscure Severe Infrarenal Aortoiliac Stenosis With Severe Transient Lactic
Acidosis.
AB - A 57-year-old man presented with sudden onset of leg pain, right-sided weakness,
aphasia, confusion, drooling, and severe lactic acidosis (15 mmol/L). He had
normal peripheral pulses and demonstrated no pain, pallor, poikilothermia,
paresthesia, or paralysis. Empiric antibiotics, aspirin, full-dose enoxaparin,
and intravenous fluid were initiated. Lactic acid level decreased to 2.5 mmol/L.
The patient was subsequently extubated and was alert and oriented with no
complaints of leg or abdominal pain. Unexpectedly, the patient developed cardiac
arrest, rebound severe lactic acidosis (8.13 mmol/L), and signs of acute limb
ischemia. Emergent computed tomography of the aorta confirmed infrarenal
aortoiliac thrombosis. Transient leg pain and transient severe lactic acidosis
can be unusual presentations of severe infrarenal aortoiliac stenosis. When in
doubt, vascular studies should be implemented without delay to identify this
catastrophic diagnosis.
PMID- 26425571
TI - Urticarial Vasculitis in a Teenage Girl.
AB - This case involves a 13-year-old female who presented to the pediatrician for a
routine check-up with complaints of a long history of intermittent diarrhea
followed by a severe rash lasting for up to a week afterwards. The mother had
described her daughter's condition to multiple physicians, several whom had seen
her during flare-ups. The nonmigratory lesions resembled "hives" with a single
lesion lasting for 48 to 72 hours and resolving into what her parent described as
a bruise. They often diagnosed her daughter with urticaria and prescribed
steroids, which did resolve the acute flare-ups. None of the physicians, however,
focused on the disease's evolution and chronicity in an effort toward diagnosis
and prevention. The patient was referred by her pediatrician to a dermatologist
who diagnosed the patient with urticarial vasculitis. She was initially started
on dapsone 25 mg and was increased over a period of months to a maintenance dose
of 100 mg daily. She has had no recurrences in her cutaneous or systemic symptoms
on this dose. She is closely monitored by her dermatologist on a regular basis
with twice yearly complete blood counts. Several attempts have been made to
discontinue the dapsone, resulting in a flare of her gastrointestinal symptoms.
This patient suffered with this condition for almost 10 years. This is a reminder
that spending extra time to think through a patient's problem early on may
prevent years of suffering for patients and their families.
PMID- 26425570
TI - Cyclophosphamide-Induced Cardiomyopathy: A Case Report, Review, and
Recommendations for Management.
AB - Cyclophosphamide is increasingly used to treat various types of cancers and
autoimmune conditions. Higher doses of this drug may produce significant cardiac
toxicity, including fatal hemorrhagic myocarditis. In this review, we present a
case of cyclophosphamide-induced cardiomyopathy requiring mechanical circulatory
support. We also describe the pathophysiology, clinical manifestations, and risk
factors for this important clinical entity and propose early detection and
management strategies.
PMID- 26425572
TI - Two Metachronous Neoplasms in the Radiotherapy Fields of a Young Man With
Familial Adenomatous Polyposis.
AB - BACKGROUND: It is recognized that various radiation-induced malignancies often
follow childhood radiotherapy. Radiation-induced neoplasms have been shown to
occur with increased frequency in syndromes due to mutated tumor suppressor
genes. There exist no recommendations for the management of cancer patients with
germline APC gene mutations. Preclinical data suggest that APC gene mutations
cause enhanced radiosensitivity, but no clinical observations exist that show
that patients with this mutation are at higher risk for radiation-induced
malignancies. RESULTS: We report the case of a 32-year-old man with a genetic
diagnosis of familial adenomatous polyposis (FAP) who initially presented at age
10 with a medulloblastoma treated with radiotherapy and surgery. Radiation
induced papillary thyroid carcinoma followed 13 years later. Finally, radiation
induced soft tissue osteosarcoma occurred with widespread metastasis 20 years
thereafter. CONCLUSIONS: This is the first report of 2 malignancies in the prior
radiotherapy fields of a patient with a genetic diagnosis of FAP. More important,
this suggests that APC-defective cells are at an enhanced sensitivity to the
carcinogenic effects of radiotherapy compared with APC-proficient cells. This
could argue for genetic screening in affected members of these families and for
creation of treatment recommendations to more seriously consider the risks of
radiation therapy.
PMID- 26425573
TI - Spontaneous Atraumatic Mediastinal Hemorrhage: Challenging Management of a Life
Threatening Condition and Literature Review.
AB - Spontaneous atraumatic mediastinal hematomas are rare. We present a case of a
previously fit and well middle-aged lady who presented with acute breathlessness
and an increasing neck swelling and spontaneous neck bruising. On plain chest
radiograph, widening of the mediastinum was noted. The bruising was later
confirmed to be secondary to mediastinal hematoma. This life-threatening
diagnostic conundrum was managed conservatively with a multidisciplinary team
approach involving upper gastrointestinal and thoracic surgeons,
gastroenterologists, radiologists, intensivists, and hematologists along with a
variety of diagnostic modalities. A review of literature is also presented to
help surgeons manage such challenging and complicated cases.
PMID- 26425574
TI - Hypercalcemia, Renal Failure, and Skull Lytic Lesions: Follicular Lymphoma
Masquerading as Multiple Myeloma.
AB - The findings of hypercalcemia, skull lytic lesions, and renal failure are usually
characteristic for multiple myeloma. We herein describe an interesting case of B
cell follicular lymphoma that presented with many features mimicking multiple
myeloma.
PMID- 26425575
TI - Recurrent Early Thrombus Formation in HeartMate II Left Ventricular Assist
Device.
AB - Left ventricular assist devices are becoming an established treatment for end
stage heart failure. In spite of their proven benefit, pump thrombosis remains a
significant complication. Here we describe the challenging management of a
patient with recurrent pump thrombosis.
PMID- 26425576
TI - When Is "Pseudo-Ludwig's Angina" Associated With Coagulopathy Also a "Pseudo"
Hemorrhage?
AB - Sublingual hematoma secondary to short-acting anticoagulants such as warfarin has
been labeled "pseudo-Ludwig's angina" to distinguish it from the classic syndrome
of localized infection and swelling involving the upper airway. Sublingual
hematoma with airway compromise secondary to brodifacoum, a common long-acting
anticoagulant rodenticide, has only been reported in the veterinary literature.
We report a case of massive tongue swelling and impending airway compromise in
the context of an intentional long-acting anticoagulant ingestion leading to
coagulopathy. The swelling was initially presumed to be due either to infection
or hemorrhage, but this was not supported by computed tomography scan imaging.
Instead, the patient's clinical course was consistent with corticosteroid
responsive angioedema, temporally associated with the ingested brodifacoum.
PMID- 26425577
TI - Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central
Nervous System Melanoma.
AB - Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary
adenomas that express adrenocorticotrophic hormone (ACTH) but do not cause the
clinical or laboratory features of hypercortisolemia. Primary central nervous
system (CNS) melanoma is well documented, but rarely originates in the sellar
region or pituitary gland. Here we report transformation of an aggressive silent
adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and
review other presentations of pituitary melanoma. A 37-year-old woman initially
presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for
which she underwent transphenoidal surgery. The patient underwent 3 subsequent
surgeries as the tumor continued to progress. Pathology from the first 3
operations showed pituitary adenoma or carcinoma. Pathology from the final
surgery showed melanoma and the magnetic resonance imaging characteristics of the
tumor had changed to become consistent with CNS melanoma. Dermatologic and
ophthalmologic examinations did not identify cutaneous or ocular melanoma. The
patient's disease progressed despite aggressive surgical, medical and radiologic
treatment. To our knowledge, this is the first report demonstrating
transformation of a primary pituitary tumor into melanoma. The mechanism of tumor
transformation is unclear, but it is possible that a mutation in the original
ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH
into alpha-melanocyte-stimulating hormone, which in turn stimulated the
expression of microopthalmia transcription factor, leading to melanocytic
phenotype transformation.
PMID- 26425578
TI - An Unusual Presentation of Isolated Leptomeningeal Disease in Carcinoma of
Unknown Primary With Pancreatic Features.
AB - Leptomeningeal disease (LMD) can occur in a small percentage of patients with
active metastatic cancer. However, we report a case of LMD occurring during
disease remission in a patient with carcinoma of unknown primary with
panreaticobiliary features. A 45-year-old woman was found with mediastinal and
abdominal lymphadenopathy with lymph node biopsy consistent with adenocarcinoma,
expressing immunomarkers CK7, CK20, and Ca19-9 along with markedly elevated serum
Ca19-9 level. The patient was started on a pancreatic cancer directed
chemotherapy regimen of Folfirinox (5-fluorouracil, leucovorin, oxaliplatin,
irinotecan) and achieved complete response. She was then noted to have slowly
rising Ca19-9 level that did not correlate with her lack of evidence of systemic
disease progression. Eventually, she presented with neurologic symptoms and was
found on imaging to have isolated LMD.
PMID- 26425579
TI - Polypoid Gallbladder Lesion in the Context of Renal Cell Carcinoma: Is
Laparoscopic Cholecystectomy a Reasonable Option?
AB - Introduction. The only curative therapeutic approach for renal cell carcinoma
(RCC) is surgery. Laparoscopic surgery for RCC has become an established surgical
procedure with equivalent cancer-free survival rate, following the same surgical
oncological principles as open surgery. Metastatic RCC of the gallbladder is a
rare phenomenon. Hence, there are few reports regarding their management. Case
Presentation. We report 2 cases of gallbladder metastasis from clear cell RCC
treated by laparoscopic cholecystectomy. The first case was that of a 44-year-old
male patient who underwent palliative cholecystectomy, the second case was that
of an 83-year-old female patient who is doing well 55 months after surgery
without evidence of disease recurrence. Conclusion. The outcome allows us to
demonstrate the interest of surgical resection of RCC metastases in the
gallbladder by laparoscopic cholecystectomy, respecting surgical oncological
principles. Laparoscopic resection of an uncommon gallbladder metastasis can
provide long-term favorable outcome.
PMID- 26425580
TI - Salter Harris Fractures of the Distal Femur: Learning Points From Two Cases
Compared.
AB - Salter Harris-type injuries of the distal femur should be treated as a
dislocation of the knee and therefore as a medical emergency. Senior medical
staff should be involved early, ankle-brachial index ratio should be measured in
all patients and the clinician should have a high index of suspicion for a
vascular injury. Ideally reduction, stabilization, and vascular repair, if
necessary, should be carried out within 6 hours of the initial event. There
should be a low threshold for fasciotomies. These 2 cases demonstrate the
importance of having a high index of suspicion for vascular injury and the need
for continued reassessment.
PMID- 26425581
TI - Clopidogrel-Induced Recurrent Polyarthritis.
AB - Clopidogrel is an oral thienopyridine and together with aspirin is a component of
dual antiplatelet therapy for the prevention of stent thrombosis after
intracoronary stent placement. The common adverse effects from its use are an
increased risk of bleeding, neutropenia, and rash. Arthralgia and backache are
also known to occur with its use. There have been case reports linking arthritis
with the use of clopidogrel. We describe the case of a 64-year-old man who
reported symptoms of fever and joint pains following initiation of therapy with
clopidogrel. Acute-phase reactants were elevated. Laboratory and radiologic
testing were unremarkable. Incidentally, he reported experiencing a similar
arthritis after he received a loading dose of clopidogrel prior to a diagnostic
coronary angiography in the past. The symptoms improved dramatically on
discontinuation of clopidogrel. There was no recurrence of symptoms with
prasugrel. This describes possibly the second incidence of recurrent arthritis
with clopidogrel therapy.
PMID- 26425582
TI - An Intriguing Endoscopic Case of Asymptomatic Crohn's Disease.
AB - We present the case of a 64-year old male with Crohn's disease, who has
intriguing endoscopic findings. Upon initial diagnosis at age 20, he received
steroid therapy, but has not required any further medical intervention. He has
remained relatively asymptomatic and keeps a healthy lifestyle. At routine
colonoscopy, we identified pseudopolyps as well as tissue bridges within the
colon, giving an unusual "swiss cheese" appearance. This case exemplifies the
heterogeneity of Crohn's disease, emphasizing the possibility of finding evidence
of ongoing disease despite lack of symptoms.
PMID- 26425583
TI - Thoracic Cavernous Lymphangioma Provoking Massive Chyloptysis: A Case Report.
AB - Chyloptysis is a relatively rare embodiment of disease that encompasses a lengthy
differential and provides many diagnostic and therapeutic challenges. Presented
here is the case of a young woman with massive chyloptysis due to a thoracic
cavernous lymphangioma arising in the peripartum period. The severity of her
condition mandated the use of cardiopulmonary bypass to resect her lymphangioma.
We believe that the extent of her symptoms, etiology of disease, and surgical
management represent a unique scenario in the literature.
PMID- 26425584
TI - rhIGF-1 Therapy for Growth Failure and IGF-1 Deficiency in Congenital Disorder of
Glycosylation Ia (PMM2 Deficiency).
AB - Background. Congenital disorders of glycosylation (CDG) are a group of rare
disorders in which glycosylation required for proper protein-protein interactions
and protein stability is disrupted, manifesting clinically with multiple system
involvement and growth failure. The insulin-like growth factor (IGF) system plays
an important role in childhood growth and has been shown to be dysfunctional with
low IGF-1 levels in children with CDG type Ia (PMM2 deficiency). Case report. A 3
year-old Caucasian male with failure to thrive was diagnosed with PMM2-CDG at 5
months of age. Initially, his length and weight were less than -2 standard
deviation score, IGF-1 <25 ng/mL (normal 55-327 ng/mL), IGFBP-3 1.0 ug/mL (normal
0.7-3.6 ng/mL), and acid-labile subunit 1.3 mg/L (normal 0.7-7.9 mg/L). Despite
aggressive feeding, he continued to show poor linear growth and weight gain. At
17 months, he underwent an IGF-1 generation test with growth hormone (0.1
mg/kg/d) for 7 days; baseline IGF-1of 27 ng/mL (normal 55-327 ng/mL) stimulated
to only 33 ng/mL. Recombinant human IGF-1 (rhIGF-1) therapy (up to 130 ug/kg/dose
twice daily) was initiated at 21 months of age resulting in an excellent linear
growth response with height increasing from -2.73 to -1.39 standard deviation
score over 22 months. IGF-1 and IGFBP-3 levels also increased. Conclusion. This
is the first case report of rhIGF-1 therapy in a patient with PMM2-CDG. The child
had an excellent linear growth response. These results provide additional in vivo
evidence for IGF dysfunction in PMM2-CDG and suggest that rhIGF-1 may be a novel
treatment for growth failure in PMM2-CDG.
PMID- 26425585
TI - Computed Tomography and Magnetic Resonance Imaging Findings of a Malignant
Hepatic Epithelioid Hemangioendothelioma: A Rare Case of Solitary Small Nodular
Form.
AB - We report the case of a rare solitary small nodular form of malignant hepatic
epithelioid hemangioendothelioma in a patient followed by computed tomography and
gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging with
histological analysis. This case showed early peripheral septal and nodular
enhancement and delayed centripetal enhancing pattern with capsular retraction,
mimicking peripheral cholangiocarcinoma, inflammatory pseudotumor, or metastases.
The histological and immunohistochemical findings were diagnostic of a malignant
hepatic epithelioid hemangioendothelioma.
PMID- 26425587
TI - A Case of Adenomyosis with a High Titer of IgG Autoantibody to Calreticulin.
AB - Background. High prevalence of autoantibodies to the calcium-binding, endoplasmic
reticulum chaperone protein calreticulin has been reported in various autoimmune
and parasitic diseases. It has been reported that adenomyosis is associated with
the presence of autoantibodies, in particular to phospholipids; however, it is
not known whether it is associated with autoimmunity to calreticulin. Results. A
35-year-old gravida 4 para 4 woman presented with a history of many years of
intractable menorrhagia. Histopathological examination of a subsequent
hysterectomy specimen revealed a bulky uterus, a poorly developed secretory
endometrium with decidualization of the stroma and chronic endometritis, as well
as the presence of adenomyosis uteri. IgG autoantibodies to calreticulin were
measured in the plasma of this and 234 other patients. Nine (3.8%) patients
tested positive. The titer of anticalreticulin IgG autoantibody in the sole case
with adenomyosis was approximately 8 times the average of other positive-testing
samples. Conclusions. The etiology of adenomyosis is unclear. The presence of a
high titer, blocking anticalreticulin autoantibody may directly increase the risk
that adenomyosis might develop. It is also possible that the expansion of
endometrial glandular tissue, as well as elevated estrogens, during adenomyosis
may lead to elevated calreticulin, which induces an autoimmune reaction to it.
Further study is required to determine whether there is a significant association
between adenomyosis and the prevalence of calreticulin autoantibodies.
PMID- 26425586
TI - Clinical Correlates of Autosomal Chromosomal Abnormalities in an Electronic
Medical Record-Linked Genome-Wide Association Study: A Case Series.
AB - Although mosaic autosomal chromosomal abnormalities are being increasingly
detected as part of high-density genotyping studies, the clinical correlates are
unclear. From an electronic medical record (EMR)-based genome-wide association
study (GWAS) of peripheral arterial disease, log-R-ratio and B-allele-frequency
data were used to identify mosaic autosomal chromosomal abnormalities including
copy number variation and loss of heterozygosity. The EMRs of patients with
chromosomal abnormalities and those without chromosomal abnormalities were
reviewed to compare clinical characteristics. Among 3336 study participants,
0.75% (n = 25, mean age = 74.8 +/- 10.7 years, 64% men) had abnormal intensity
plots indicative of autosomal chromosomal abnormalities. A hematologic malignancy
was present in 8 patients (32%), of whom 4 also had a solid organ malignancy
while 2 patients had a solid organ malignancy only. In 50 age- and sex-matched
participants without chromosomal abnormalities, there was a lower rate of
hematologic malignancies (2% vs 32%, P < .001) but not solid organ malignancies
(20% vs 24%, P = .69). We also report the clinical characteristics of each
patient with the observed chromosomal abnormalities. Interestingly, among 5
patients with 20q deletions, 4 had a myeloproliferative disorder while all 3 men
in this group had prostate cancer. In summary, in a GWAS of 3336 adults, 0.75%
had autosomal chromosomal abnormalities and nearly a third of them had
hematologic malignancies. A potential novel association between 20q deletions,
myeloproliferative disorders, and prostate cancer was also noted.
PMID- 26425588
TI - A Spontaneously Ruptured Hepatic Metastasis From a Gastric Gastrointestinal
Stromal Tumor That Presented as Hemoperitoneum.
AB - Spontaneous hepatic hemorrhage is a rare condition that may be caused by an
underlying hepatic tumor, most commonly hepatocellular carcinoma or hepatic
adenoma. A spontaneous rupture of a hepatic metastasis from a gastric
gastrointestinal stromal tumor is also extremely rare, and the majority of
affected patients present with hypovolemic shock or an acute abdomen. In this
article, we report the case of a 65-year-old man with a spontaneous rupture of a
hepatic metastasis from a gastric gastrointestinal stromal tumor that presented
as hypovolemic shock. Cross-sectional imaging studies (computed tomography or
magnetic resonance imaging) play a significant role in the diagnosis of this
condition and guides its management.
PMID- 26425589
TI - Fixed Drug Eruption in an Epileptic Patient Previously Receiving Treatment With
Phenytoin for Seven Years.
AB - A 52-year-old African American female presented with severe left thigh pain of
unknown etiology. She had a past medical history of generalized seizure disorder
treated with phenytoin for 7 years without incident. During admission a nurse
witnessed a seizure, and consequently loading and maintenance doses of phenytoin
were administered to obtain a therapeutic serum concentration. The patient had a
history of noncompliance with multiple subtherapeutic phenytoin levels.
Subsequently, unifocal blue discolored spots appeared, progressing to a bullous
component that was positive for skin sloughing. Drug-induced fixed drug eruption
was diagnosed and attributed to phenytoin. Clinicians should be cognizant of drug
induced fixed drug eruption in patients just initiated and those receiving long
term treatment with phenytoin. The administration rate of phenytoin may be
associated with the development of fixed drug eruption.
PMID- 26425590
TI - Isolated Pulmonary Valve Endocarditis Complicated With Septic Emboli to the Lung
Causing Pneumothorax, Pneumonia, and Sepsis in an Intravenous Drug Abuser.
AB - Intravenous drug users are at increased risk for developing right-sided infective
endocarditis involving the tricuspid and pulmonary valves. Isolated pulmonary
valve endocarditis in intravenous drug users is very rare, and these patients
often have more complications, such as pulmonary embolism, sepsis, and pneumonia.
We report a case with pulmonary valve endocarditis and extensive pulmonary
complications, including sepsis, septic emboli, pneumonia, and pneumothorax.
Early identification of pulmonic valve endocarditis and treatment with
appropriate antibiotics with or without surgical management should provide better
outcomes, and clinicians need to think about pulmonary valve endocarditis in
patients with complex respiratory presentations.
PMID- 26425591
TI - Drug-Induced Liver Injury by Glatiramer Acetate Used for Treatment of Multiple
Sclerosis: A Case Report.
AB - Glatiramer acetate (GA, Copaxone) is an approved drug for the treatment of
relapsing-remitting multiple sclerosis. Most common side effects observed with GA
are local injection site reactions, which can include pain, swelling, or redness.
However, systemic adverse event such as hepatotoxicity related to GA is rarely
seen. In this report, we present a case of GA-induced toxic hepatitis associated
with cholestatic and hepatocellular damage.
PMID- 26425592
TI - Late Onset of CSF Rhinorrhea in a Postoperative Transsphenoidal Surgery Patient
Following Robotic-Assisted Abdominal Hysterectomy.
AB - Cerebrospinal fluid (CSF) leak is the most commonly encountered perioperative
complication in transsphenoidal surgery for pituitary lesions. Direct closure
with a combination of autologous fat, local bone, and/or synthetic grafts remains
the standard of care for leaks encountered at the time of surgery as well as
postoperatively. The development of the vascularized nasoseptal flap as a closure
technique has increased the surgeon's capacity to correct even larger openings in
the dura of the sella as well as widely exposed anterior skull base defects. Yet
these advances in the technical nuances for management of post-transsphenoidal
CSF leak are useless without the ability to recognize a CSF leak by physical
examination, clinical history, biochemical testing, or radiographic assessment.
Here, we report a case of a patient who developed a CSF leak 28 years after
transsphenoidal surgery, precipitated by a robotic-assisted hysterectomy during
which increased intra-abdominal pressure and steep Trendelenberg positioning were
both factors. Given the remote nature of the patient's transsphenoidal surgery
and relative paucity of data regarding such a complication, the condition went
unrecognized for several months. We review the available literature regarding
risk and pathophysiology of CSF leak following abdominal surgery and propose the
need for increased vigilance in identification of such occurrences with the
increasing acceptance and popularity of minimally invasive abdominal and pelvic
surgeries as standards in the field.
PMID- 26425593
TI - Perioperative Outcome of Dyssomnia Patients on Chronic Methylphenidate Use.
AB - Methylphenidate is frequently prescribed for attention deficit hyperactivity
disorder, narcolepsy, and other sleep disorders requiring psychostimulants. Our
report is based on 2 different clinical experiences of patients with chronic
methylphenidate use, undergoing general anesthesia. These cases contrast
different strategies of taking versus withholding the drug treatment on the day
of surgery. From the standpoint of anesthetic management and patient safety, the
concerns for perioperative methylphenidate use are mainly related to
cardiovascular stability and possible counteraction of sedatives and anesthetics.
PMID- 26425594
TI - Right-Sided Pleural Effusion in a Critically Ill Stroke Patient.
AB - Pleural fluid collections are common in those critically ill. We report the case
of a left middle cerebral artery stroke patient who developed respiratory
distress and required intubation and mechanical ventilation. Although the
patient's clinical status and oxygenation improved, there was persistence of
right-sided opacity in the chest radiograph. Further workup proved a right-sided
pleural effusion, which was drained and managed. Following extubation, a swallow
study was ordered, which led to a fluoroscopic examination that demonstrated
esophageal perforation. Thoracic surgery was consulted and did a primary repair
of perforation and noted non-small cell carcinoma on the perforated site.
PMID- 26425595
TI - Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge.
AB - Case Presentation. A 69-year-old Hispanic male, with a past history of diabetes
and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks
duration. Physical examination showed a disoriented patient with multiple
ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7,
prothrombin time (PT) 21.4 seconds with international normalized ratio 2.1,
partial thromboplastin time (PTT) 55.6 seconds, fibrin split 10 ug/L, and lactate
dehydrogenase (LDH) 1231 IU/L. Except for a positive DNA test for Epstein-Barr
virus (EBV) infection, extensive diagnostic workup for infections, malignancy, or
a neurological cause was negative. Mixing studies revealed a nonspecific
inhibitor of PT and PTT but Factor VIII levels were normal. The patient was
empirically treated with antibiotics but developed hypotension and died on day 27
of admission. At autopsy, patient was found to have intravascular diffuse large B
cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were
positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30,
and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion.
Intravascular large cell B-cell lymphoma (IVLBCL) is rare form of diffuse large B
cell lymphoma and tends to proliferate within small blood vessels, particularly
capillaries and postcapillary venules. The cause of its affinity for vascular bed
remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV
infections. The fact that our case showed evidence of EBV infection lends support
to the association of this diagnosis to viral illness. The available literature
on this subject is scant, and in many cases, the diagnosis was made only at
autopsy. The typical presentation of this disorder is with B symptoms,
progressive neurologic deficits, and skin findings. Bone marrow, spleen, and
liver are involved in a minority of patients. Nearly all patients have elevated
LDH, and about 65% are anemic. About 20% have hepatic and renal dysfunction. The
treatment consists of systemic chemotherapy with cyclophosphamide, doxorubicin,
vincristine, prednisone plus rituximab (CHOP-R) and central nervous system
prophylaxis. Retrospective data suggests that, with treatment, 51% to 82% of the
patients achieve a complete remission and 27% to 56% are alive at 2-year follow
up. Conclusion. IVLBCL is a difficult diagnosis to make as the disease remains
confined to the vascular lumen. It may be associated with certain viral
illnesses, and this association needs to be explored further. It is important to
consider this diagnosis in the appropriate settings because patients may achieve
durable remissions with therapy.
PMID- 26425596
TI - Reversible Adrenal Insufficiency in Three Patients With Post-Roux-en-Y Gastric
Bypass Noninsulinoma Pancreatogenous Hypoglycemia Syndrome.
AB - Objective. Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a
disorder of endogenous hyperinsulinemia that is clinically distinguishable from
insulinoma, with a greater preponderance after Roux-en-Y gastric bypass (RYBG).
Hyperinsulinemic hypoglycemia can predispose to attenuation of counterregulatory
hormone responses to hypoglycemia, and consequent suppression of the hypothalamic
pituitary-adrenal (HPA) axis. This case series describes 3 individuals who were
diagnosed with adrenal insufficiency (AI) after undergoing RYGB, complicated by
NIPHS. Methods. A retrospective chart review was performed for each individual.
Chart review applied particular attention to the onset of hyperinsulinemic
hypoglycemia following bariatric surgery and the dynamic testing leading to the
diagnoses of NIPHS and AI. Results. In each case, reactive hypoglycemia ensued
within months to years after RYGB. Cosyntropin stimulation testing confirmed the
diagnosis of AI. Hydrocortisone therapy reduced the frequency and severity of
hypoglycemia and was continued until successful medical and/or surgical
management of hyperinsulinism occurred. Follow-up testing of the HPA axis
demonstrated resolution of AI. In all cases, hydrocortisone therapy was finally
discontinued without incident. Conclusion. We speculate that transient AI is a
potential complication in patients who experience recurrent hyperinsulinemic
hypoglycemia after RYGB. The putative mechanism for this observation may be
attenuation of the HPA axis after prolonged exposure to severe, recurrent
hypoglycemia. We conclude that biochemical screening for AI should be considered
in individuals who develop post-RYGB hyperinsulinemic hypoglycemia. If AI is
diagnosed, supportive treatment should be maintained until hyperinsulinemic
hypoglycemia has been managed effectively.
PMID- 26425597
TI - Long-Term Hypoparathyroidism and Hypophosphatemia in Dialysis Patients.
AB - Background and Objectives. Hypoparathyroidism in patients with functioning
kidneys leads to hyperphosphatemia. This article reviews data suggesting that
hypoparathyroidism in patients on dialysis leads to hypophosphatemia. Design.
Clinical data of the following were reviewed: (a) a patient with
hypoparathyroidism before and during chronic dialysis; (b) patients on dialysis
with surgically created hypoparathyroidism; (c) dialysis patients being treated
with Cinacalcet, a calcium-sensing receptor agonist that lowers parathyroid
hormone (PTH) levels; and (d) dialysis patients being treated with Velcalcetide,
a new calcium-sensing receptor agonist that also lowers PTH. Results. In the
patient presented in this study, in patients with surgically created
hypoparathyroidism, and those receiving Cinacalcet or Velcalcetide, a fall in PTH
was associated with hypophosphatemia or a fall in serum phosphorus. Conclusion.
In patients on dialysis, hypoparathyroidism may lead to hypophosphatemia.
PMID- 26425598
TI - Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as
Part of the "Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants": Case
Report and Literature Review.
AB - We report the case of a 14-year-old girl who developed postural orthostatic
tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil
vaccination. The patient suffered from persistent headaches, dizziness, recurrent
syncope, poor motor coordination, weakness, fatigue, myalgias, numbness,
tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment,
insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The
psychiatric evaluation ruled out the possibility that her symptoms were
psychogenic or related to anxiety disorders. Furthermore, the patient tested
positive for ANA (1:1280), lupus anticoagulant, and antiphospholipid. On clinical
examination she presented livedo reticularis and was diagnosed with Raynaud's
syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory
syndrome induced by adjuvants (ASIA). Because human papillomavirus vaccination is
universally recommended to teenagers and because POTS frequently results in long
term disabilities (as was the case in our patient), a thorough follow-up of
patients who present with relevant complaints after vaccination is strongly
recommended.
PMID- 26425599
TI - Ineffectual Medical Treatment of Cesarean Scar Ectopic Pregnancy With Systemic
Methotrexate: A Report of Two Cases.
AB - The implantation of a pregnancy within the scar of a previous cesarean section is
known as a "cesarean scar pregnancy." Its incidence was reported to be 6.1%.
However, with the increasing rates of cesarean sections, the incidence is
expected to rise. A variety of conservative and surgical treatment modalities
have been proposed for the management of cesarean scar pregnancy; however, there
are no optimal universal treatment guidelines because of its rarity. Treatment
should be tailored to the individual patient. It is obvious that more scar
pregnancies will be seen in the future and therefore a set of criteria for the
choice of various modes of management should be developed. Here, we present 2
cases of cesarean scar pregnancies treated with a local injection of potassium
chloride after the failure of methotrexate administration.
PMID- 26425600
TI - Pulmonary Artery Sarcoma: A Rare Entity.
AB - Pulmonary artery sarcomas (PAS) are extremely rare sarcomas of uncertain
histogenesis that often mimic pulmonary thromboemboli. This is a report of a 60
year-old female patient who presented with recurrent chest pain and cough. The
patient was first diagnosed with pulmonary embolism but she did not improve on
anticoagulant therapy. Follow-up imaging studies revealed a mass in the left
hilar region extending into the pulmonary trunk and branches of the left
pulmonary artery. The tru-cut biopsy revealed an undifferentiated sarcoma. The
patient died 10 months after her initial presentation.
PMID- 26425601
TI - Neuroborreliosis Mimicking Leptomeningeal Carcinomatosis in a Patient With Breast
Cancer: A Case Report.
AB - Leptomeningeal carcinomatosis is a serious complication of advanced cancer.
Various clinical manifestations may present, such as headache, nausea, seizures,
cranial neuropathies. In this article, we report the case of a 65-year-old woman
with metastatic breast cancer who was admitted to hospital suffering from facial
palsy, which was suspected to be caused by leptomeningeal tumor infiltration.
Magnetic resonance imaging (MRI) scans of the head and spine showed meningeal
enhancement of the facial nerve, conus medullaris, and fibers of the cauda
equina, which were radiologically interpreted as leptomeningeal carcinomatosis.
Assessment of cerebrospinal fluid found no malignant cells but investigation for
infectious diseases established the diagnosis of neuroborreliosis. Antibiotic
treatment with doxycycline was performed. After completion of treatment, follow
up MRI scans found complete regression of meningeal enhancement. Several months
later, the patient is still in good condition and without neurological symptoms.
Hence, initial diagnosis of leptomeningeal carcinomatosis was rejected. This case
report should alert oncologists to carefully rule out infectious diseases before
leptomeningeal carcinomatosis is diagnosed. Cerebrospinal fluid analysis is
strongly recommended due to low specificity of MRI images in this regard.
PMID- 26425602
TI - Herpes Simplex Pneumonia in an Immunocompetent Patient With Progression to
Organizing Pneumonia.
AB - Background. Organizing pneumonia is an uncommon diffuse interstitial lung disease
that affects the terminal and respiratory bronchioles, alveolar ducts, and
alveoli. Most cases are idiopathic, but some are associated with infections. We
present an uncommon case of organizing pneumonia associated with herpes simplex
virus-1 (HSV-1). Case. A 39-year-old man with hypertension presented with
dyspnea, fever, and productive cough for 2 weeks. He was treated for 5 days for
acute bronchitis as an outpatient with no improvement. His examination revealed
mild respiratory distress, O2 saturation 92% on room air, and right sided
crackles. Labs included a white blood cell count of 19 300/uL. His chest x-ray
showed bilateral infiltrates greater on the right. Bronchoalveolar lavage was
positive for HSV-1; transbronchial biopsies showed focal pneumonitis with
plentiful intra-alveolar macrophages. His respiratory status progressively
deteriorated, and he was intubated for mechanical ventilation. He received 10
days of intravenous (IV) antibiotics and 14 days of IV acyclovir. He was
readmitted 10 days later with worsening symptoms and was intubated for
respiratory failure. His CT chest showed diffuse, patchy consolidation of both
lungs, right more than left. Open lung biopsy showed extensive organizing
pneumonia, diffuse alveolar damage, intra-alveolar macrophages, and pleural
fibrosis; he was treated with IV corticosteroids. He was extubated after 10 days;
within 2 weeks his chest x-ray was markedly improved. Discussion. Organizing
pneumonia is usually idiopathic; infection is one of the secondary causes. To our
knowledge this is only the second reported case associated with HSV. This
association may have important pathogenic and therapeutic implications.
PMID- 26425603
TI - Spontaneous Heterotopic Triplet Pregnancy With Tubal Rupture: A Case Report and
Literature Review.
AB - The recent increase in heterotopic pregnancies has been largely attributed to the
increased use of assisted reproduction technologies. We report the rare case of a
multiparous woman with a spontaneous conception resulting in a triplet
heterotopic pregnancy: a twin intrauterine pregnancy and a single right tubal
ectopic pregnancy. Heterotopic pregnancy is a rare and potentially life
threatening condition in which simultaneous gestations occur at 2 or more
implantation sites. It is infrequent in natural conception cycles, occurring in
1:30 000 pregnancies. However, the prevalence is rising with the increased use of
assisted reproduction techniques to that of 1:100 to 1:500 in these patient
subgroups, highlighting the need to incorporate it into a clinician's diagnostic
algorithm.
PMID- 26425604
TI - Medulloblastoma in an Adult With Late Extraneural Metastases to the Mediastinum.
AB - Background. Medulloblastoma, although the most common brain tumor of childhood,
is exceedingly rare in adults. These tumors have a propensity for local
recurrence and to metastasize along the leptomeninges; however, extraneural
metastases are very rare and typically occur in the bone or bone marrow. We have
not come across any case in literature of medulloblastoma with mediastinal
metastases in an adult. Case Presentation. We report a case of medulloblastoma in
a 38-year-old lady who was treated with surgery followed by craniospinal
radiation. Ten years later she presented with hoarseness from true vocal cord
paralysis. She was diagnosed to have infiltrating metastases of her
medulloblastoma to the mediastinum, which was confirmed by biopsy. There was no
local recurrence. This was treated with chemotherapy followed by stem cell
rescue, and she remained progression free for 2 years. Conclusion.
Medulloblastomas are rare in adults and can present with late extraneural
metastases following treatment. Although most common reported sites are bone and
bone marrow, late metastases to other unexpected areas like the mediastinum are
possible too and warrant awareness. This can be treated with chemotherapy
followed by high-dose chemotherapy and stem cell rescue in a young patient with
good performance status.
PMID- 26425606
TI - Cholestatic Jaundice With the Use of Methylstenbolone and Dymethazine, Designer
Steroids Found in Super DMZ Rx 2.0 "Nutritional Supplement": A Case Report.
AB - "Nutritional supplements" that promise an increase in muscle mass and strength
are becoming a go to item as enhancing one's physical appearance becomes a more
important part of our society. This is alarming because many of these nutritional
supplements rely on androgen precursors to deliver their promises, without
adequately informing consumers of the potential side effects of such agents.
These products may conceal the presence of potent androgens to avoid regulatory
sanctions and become more appealing to consumers. Recent reports have shown that
some products marketed as "nutritional supplements" have been found to contain
androgenic anabolic steroids. Methylstenbolone and dymethazine are new androgenic
anabolic steroids currently gaining popularity among body builders for their
performance-enhancing properties and rapid effects on muscle mass. These agents
are found together in Super DMZ Rx 2.0, a "dietary supplement" for bodybuilders.
Here we report the first case of Super DMZ Rx 2.0-induced cholestatic jaundice in
a 26-year-old previously healthy Caucasian male, who took the supplement
according to the manufacturer's instructions for 30 days.
PMID- 26425607
TI - Fever Through a Jaundiced Eye.
AB - Pyogenic liver abscess (PLA) is an important clinical entity to consider in a
patient with fever and abdominal pain. Previously, the condition was difficult to
diagnose and treat, but with the introduction of widely available and reliable
imaging techniques, its diagnosis has become more straightforward. Although
uncommon, PLA should especially be considered in the differential diagnosis for
patients with specific predisposing conditions such as underlying biliary tract
disease, whether as a result of chronic inflammatory disease or malignancy. The
introduction of percutaneous drainage has revolutionized the management of PLA,
and thus, this disease has become largely correctable.
PMID- 26425605
TI - Ultrasound Detection of Salmonella Septic Arthritis in a Rheumatoid Arthritis
Patient on Anti-TNF Treatment.
AB - We report a case of Salmonella septic arthritis detected by ultrasound in a 40
year-old man with rheumatoid arthritis while he was on anti-tumor necrosis factor
alpha monoclonal antibody certolizumab. An aspirate of his left elbow joint
showed Salmonella enteritidis infection that was sensitive to ceftraixone. This
was preceded by a brief episode of loose stools following a visit to the Far
East. He was treated with antibiotics and made a good recovery. There have only
been a few case reports of Salmonella septic arthritis in a rheumatoid arthritis
patient on anti-tumor necrosis factor treatment but none previously in
association with certolizumab.
PMID- 26425608
TI - Immune Reconstitution Inflammatory Syndrome in Acquired Immune Deficiency
Syndrome related to Cryptococcal Meningoencephalitis.
AB - Background. Highly active antiretroviral therapy (HAART) has contributed to
reducing the occurrence of opportunistic infections and mortality in human
immunodeficiency virus (HIV) infected patients. However, a paradoxical worsening
of clinical signs and symptoms among patients during HAART may occur. Immune
reconstitution inflammatory syndrome (IRIS) is described as a paradoxical
deterioration of clinical status on initiation of HAART in patients with HIV
infection. Case Report. We describe the case of a 41-year-old man with
opportunistic cryptococcal encephalitis who exhibited neurological and
radiological deterioration during the course of HAART. A diagnosis of central
nervous system (CNS)-IRIS was based on a decrease of HIV-RNA viral load greater
than 1 log, with an increase in CD4(+) T-cell count from baseline. Conclusions.
Differential diagnosis of this paradoxical deterioration in clinical and
neurological status from overwhelming opportunistic infection is important; it
enables an avoidance of unnecessary diagnostic procedures and proper management
of this HIV-associated CNS disorder.
PMID- 26425609
TI - Brachial Neuritis With Phrenic Nerve Involvement in a Patient With a Possible
Connective Tissue Disease.
AB - Background. Brachial neuritis (BN) is a rare inflammatory condition of peripheral
nerves, usually involving the cervicobrachial plexus. These patients present with
sudden onset of shoulder and arm pain that evolves into muscle weakness and
atrophy.. Case Report. A 33-year-old woman presented with a 1-month history of
diffuse pain in her thorax. She had no trauma or inciting incident prior to the
onset of this pain and was initially treated for muscle spasms. The patient was
seen in the emergency room multiple times and was treated with several courses of
antibiotics for pneumonia on the basis of clinical symptoms and abnormal x-rays.
The pleuritic chest pain persisted for at least 4 months, and the patient was
eventually admitted for worsening pain and dyspnea. On physical examination,
crackles were heard at both lung bases, and chest inspection revealed increased
expansion in the upper thorax but poor expansion of the lower thorax and mild
paradoxical respiration. "Sniff" test revealed no motion of the left
hemidiaphragm and reduced motion on the right hemidiaphragm. Her computed
tomography scan revealed bilateral atelectasis, more severe at the left base. She
reported no symptoms involving her joints or skin or abdomen. Her presentation
and clinical course are best explained by BN with a bilateral diaphragmatic
weakness. However, she had a positive ANA, RF, anti-RNP antibody, and anti SS-A.
Conclusion. Patients with BN can present with diffuse thoracic pain, pleuritic
chest pain, and diaphragmatic weakness. Our patient may represent a case of
connective tissue disease presenting with brachial plexus neuritis.
PMID- 26425610
TI - Tension Pneumothorax During Surgery for Thoracic Spine Stabilization in Prone
Position: A Case Report and Review of Literature.
AB - The intraoperative progression of a simple or occult pneumothorax into a tension
pneumothorax can be a devastating clinical scenario. Routine use of prophylactic
thoracostomy prior to anesthesia and initiation of controlled ventilation in
patients with simple or occult pneumothorax remains controversial. We report the
case of a 75-year-old trauma patient with an insignificant pneumothorax on the
right who developed an intraoperative tension pneumothorax on the left side while
undergoing thoracic spine stabilization surgery in the prone position. Management
of an intraoperative tension pneumothorax requires prompt recognition and
treatment; however, the prone position presents an additional challenge of
readily accessing the standard anatomic sites for pleural puncture and air
drainage.
PMID- 26425611
TI - Mitral Valve Annuloplasty Ring Dehiscence Diagnosed Intraoperative With Real-Time
3D Transesophageal Echocardiogram.
AB - Mitral annular calcification (MAC) is often a result of the accumulation of
lipids around the annulus, which can lead to degeneration and calcification of
the valve. Multiple risk factors have been associated with the progression of MAC
and life-threatening complications such as the early mitral valve annuloplasty
dehiscence. Our case describes the different risk factors for annuloplasty
dehiscence in a patient with severe MAC, as well as the importance of its early
recognition intraoperatively with 3D transesophageal echocardiography.
PMID- 26425612
TI - Trousseau's Syndrome, a Previously Unrecognized Condition in Acute Ischemic
Stroke Associated With Myocardial Injury.
AB - Trousseau's syndrome is a well-known malignancy associated hypercoagulative state
leading to venous or arterial thrombosis. The pathophysiology is however poorly
understood, although multiple mechanisms are believed to be involved. We report a
case of Trousseau's syndrome resulting in concomitant cerebral and myocardial
microthrombosis, presenting with acute ischemic stroke and markedly elevated
plasma troponin T levels suggesting myocardial injury. Without any previous
medical history, the patient developed multiple cerebral infarctions and died
within 11 days of admission. The patient was postmortem diagnosed with an
advanced metastatic adenocarcinoma of the prostate with disseminated cerebral,
pulmonary, and myocardial microthrombosis. Further analyses revealed, to the best
of our knowledge for the first time in stroke patients, circulating microvesicles
positive for the epithelial tumor marker CK18 and citrullinated histone H3 in
thrombi, markers of the recently described cancer-associated procoagulant DNA
based neutrophil extracellular traps. We also found tissue factor, the main in
vivo initiator of coagulation, both in thrombi and in metastases. Troponin
elevation in acute ischemic stroke is common and has repeatedly been associated
with an increased risk of mortality. The underlying pathophysiology is however
not fully clarified, although a number of possible explanations have been
proposed. We now suggest that unexplainable high levels of troponin in acute
ischemic stroke deserve special attention in terms of possible occult malignancy.
PMID- 26425613
TI - Hepatic Dysfunction as a Paraneoplastic Manifestation of Metastatic Prostate
Adenocarcinoma.
AB - Cholestasis is a general feature of intrahepatic or extrahepatic biliary
obstruction by various mechanisms including cirrhosis, stricture,
choledocholithiasis, hepatitis, and neoplasms. Neoplasms can directly impinge on
the hepatobiliary tree resulting in bile stasis. Stauffer's syndrome is another
variant of this neoplastic process that can cause cholestasis and liver enzyme
elevation without any direct hepatobiliary obstruction, and is thus categorized
as a paraneoplastic syndrome of unclear pathophysiology. We report a first case
of metastatic prostate adenocarcinoma with features of Stauffer's syndrome that
reversed completely on androgen deprivation therapy. This is in contrast to a
previously reported case of Stauffer's syndrome due to metastatic prostate
adenocarcinoma, which reversed partially to androgen deprivation therapy. Our
case demonstrates the importance of early recognition of Stauffer's syndrome and
underlying neoplasms in patients who present with cholestasis without clear
evidence of intrahepatic or extrahepatic biliary obstruction, which may lead to
early initiation of treatment.
PMID- 26425614
TI - Abnormal Origin of the Right Pulmonary Artery From Ascending Aorta (Hemitruncus
Arteriosus).
AB - Hemitruncus arteriosus is a rare congenital deformity that results in early
infant mortality. Persistence into adulthood is very unusual and is associated
with pulmonary hypertension. We report a case in an adult male with the
associated clinical issues.
PMID- 26425616
TI - Tumor Lysis Syndrome in a Retroperitoneal Sarcoma.
AB - In the present case, a 49-year-old white female presented to the clinic with a 2
month history of nausea, vomiting, and right upper quadrant pain. On examination
a 3-cm mass on the right anterior scalene muscle was noted. A computed tomography
scan was performed revealing a 8.7 * 7.7 * 6.1 cm retroperitoneal mass with
possible invasion of the inferior vena cava and right renal and left common iliac
veins. An excisional biopsy was performed with pathology compatible with spindle
cell sarcoma. The patient was then sent for follow-up at the sarcoma clinic as an
outpatient. However, before chemotherapy was to be started the patient would be
admitted to the hospital with progressively worse nausea and vomiting. At that
time the patient's lab work showed lactic acidosis, acute renal failure,
hyperuricemia, hyperphosphatemia, and hypocalcemia, which met the Cairo-Bishop
criteria for tumor lysis syndrome (TLS). The patient was admitted to the
intensive care unit and kidney dialysis initiated. The patient would become
progressively obtunded at which time the family opted for hospice care. The
patient eventually succumbed peacefully 3 days after her last admission. In this
case report, we briefly review the literature on TLS in solid tumors, and we
present a rare case of spontaneous TLS in a retroperitoneal sarcoma.
PMID- 26425615
TI - Acute Surgical Abdomen: An Unusual Presentation of Pulmonary Embolus.
AB - Background. Pulmonary embolism is a common and potentially lethal condition. Most
patients who die from massive pulmonary embolism do so within the first few hours
of the event. The clinical manifestations of pulmonary embolism are nonspecific,
which makes the diagnosis difficult. Case Report. We present a case of massive
pulmonary embolism presenting as an acute surgical abdomen that underwent
exploratory laparotomy and made a complete recovery. Why should an emergency
physician be aware of this? Emergency department physicians should be aware that
massive pulmonary embolism could present as an acute surgical abdomen in young
healthy individuals.
PMID- 26425617
TI - Follicular Thyroid Carcinoma Presenting With Endobronchial Metastases: Case
Report and Review of Literature.
AB - Endobronchial metastasis is a rare manifestation of differentiated thyroid
cancer. A 79-year-old male was admitted to the hospital with shortness of breath,
chest pain, anemia, and weight loss. Computed tomography of chest revealed
multiple lung nodules. Bronchoscopy showed an endobronchial lesion in the right
upper lobe. The biopsy of the lesion demonstrated neoplastic cells stained
positive for thyroglobulin, thyroid transcription factor-1, and cytokeratin-7,
consistent with metastatic follicular thyroid cancer. Physical examination
revealed a firm fixed thyroid nodule, which was confirmed by thyroid ultrasound.
He subsequently underwent total thyroidectomy and neck exploration. Thyroid gland
pathology revealed a nodule with features of high-grade follicular thyroid
carcinoma. Metastatic thyroid cancer should be considered in workup of pulmonary
nodules. We recommend an examination of thyroid gland in patients who present
with pulmonary nodules associated with signs and symptoms of malignancy.
PMID- 26425618
TI - Permanent Peripheral Neuropathy: A Case Report on a Rare but Serious Debilitating
Side-Effect of Fluoroquinolone Administration.
AB - The health risks and side effects of fluoroquinolone use include the risk of
tendon rupture and myasthenia gravis exacerbation, and on August 15, 2013, the
Food and Drug Administration updated its warning to include the risk of permanent
peripheral neuropathy. We present a case of fluoroquinolone-induced peripheral
neuropathy in a patient treated for clinically diagnosed urinary tract infection
with ciprofloxacin antibiotic.
PMID- 26425619
TI - Belatacept for Maintenance Immunosuppression in Lung Transplantation.
AB - Belatacept is a novel immunosuppressant that blocks a T-cell costimulation
pathway and is approved for use in adult kidney transplant recipients. Its safety
and efficacy have not been established after lung transplantation. We present a
case of a lung transplant recipient treated with belatacept. A 56-year-old man
underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome
(BOS). In the third year posttransplant, he developed hemolytic uremic syndrome
(HUS) attributed to tacrolimus. Tacrolimus was changed to sirolimus. One month
later, he presented with worsening renal function and HUS attributed to
sirolimus. Plasmapheresis and steroid pulse were initiated with clinical
improvement, and sirolimus was switched to belatacept. He experienced no episodes
of cellular rejection but developed recurrent BOS. Complications during treatment
included anemia and recurrent pneumonias. The safety and efficacy of belatacept
in lung transplantation remains unclear; further studies are needed.
PMID- 26425620
TI - Carotid Stump Syndrome: Case Report and Endovascular Treatment.
AB - Objectives. To highlight the case of a patient with multiple transient ischemic
attacks and visual disturbances diagnosed with carotid stump syndrome and managed
with endovascular approach. Case Presentation. We present the case of a carotid
stump syndrome in an elderly patient found to have moderate left internal carotid
artery stenosis in response to an advertisement for carotid screening. After a
medical therapeutic approach and a close follow-up, transient ischemic attacks
recurred. Computed tomographic angiography showed an occlusion of the left
internal carotid artery and the presence of moderate stenosis in the right
internal carotid artery, which was treated by endovascular stenting and balloon
insertion. One month later, the patient presented with visual disturbances due to
the left carotid stump and severe stenosis of the left external carotid artery
that was reapproached by endovascular stenting. Conclusion. Considerations should
be given to the carotid stump syndrome as a source of emboli for ischemic
strokes, and vascular assessment could be used to detect and treat this syndrome.
PMID- 26425621
TI - Severe Osteomalacia Related to Long-Term Intravenous Drug Abuse.
AB - Objective. We present the clinical, biochemical, and imaging findings of a woman
with vitamin D deficiency and severe osteomalacia related to intravenous heroin
addiction. Results. A 54-year-old woman with a medical history significant for
long-standing heroin abuse presented with complaints of bone pain, muscle
cramping, and a left hip ulcer. She had been bed bound for approximately 1 year
secondary to pain of uncertain etiology, and her husband was bringing her both
food and drugs. She was admitted to the hospital for debridement of a right
ischial ulcer. Further workup revealed osteomyelitis of the left hip and severe
vitamin D deficiency. Radiologic evaluation demonstrated diffuse osteopenia with
pseudofractures, as well as true fractures. Conclusion. This is the first case
reported in the English literature of advanced osteomalacia resulting from a
debilitating narcotic dependency. Vitamin D deficiency should be considered in
patients with poor nutrition and prolonged sunlight deprivation from any cause.
PMID- 26425622
TI - When Coke Is Not Hydrating: Cocaine-Induced Acute Interstitial Nephritis.
AB - A 47-year-old African American man was admitted with 4 days of back pain, nausea
and vomiting, and low urine output. There was no history of fever, dysuria,
frequency, hesitancy, viral symptoms, trauma, rash, or constipation. Despite his
past medical history of hypertension, diabetes mellitus, and hyperlipidemia he
denied taking any medications for 18 months, including nonsteroidal anti
inflammatory drugs, acetaminophen, or antacids. He denied smoking and alcohol but
admitted to cocaine use. No significant FH. Physical examination results were as
follows: BP 235/125 mm Hg, heart rate 90 beats/min, temperature 98 degrees F, O2
saturation normal; lungs and heart normal, abdomen soft but bilateral
costovertebral angle tenderness. Neurological examination was normal. Laboratory
tests yielded the following results: creatinine (Cr) 10.5 mg/dL (1.2 mg/dL in
2010), blood urea nitrogen 63 mg/dL, glucose 151 mg/dL, Ca 9.4 mg/dL, PO4 6.1
mg/dL, Hgb 15 g/dL, white blood cells (WBC) 9100, platelets 167 000,
amylase/lipase normal, aspartate aminotransferase/alanine aminotransferase
(AST/ALT) normal, bilirubin 1.4 mg/dL, alkaline phosphatase 39 IU/L, creatine
phosphokinase 127 ug/L. Hepatic panel, C- and P-ANCA (cytoplasmic- and
perinuclear-antineutrophil cytoplasm antibodies, respectively), anti-GBM (anti
glomerular basement membrane), antimyeloperoxidase, antinuclear antibody, and
Helicobacter pylori were all negative. C3, C4 normal, urinalysis: 2+ blood, no
white blood cells or eosinophils, no casts, no albumin, negative for
nitrate/leukocyte esterase and bacteria. Imaging: chest radiograph, abdominal
radiograph, computed tomography of the abdomen, electrocardiography, and
transthoracic echocardiography were all normal. Course. The patient's urine
output declined from 700 to 400 cm(3)/d and the on third day he required
hemodialysis with Cr 14 mg/dL. Renal biopsy showed typical findings of
interstitial nephritis. The patient was dialyzed for 10 days and responded to
steroids and went home with an improving Cr of 3.5 mg/dL, back to baseline of 1.5
in 8 weeks. Discussion. Internists encounter patients with acute kidney injury
(AKI) on a daily basis, most of which can be explained by prerenal azotemia,
acute tubular necrosis (ATN), obstruction, or rhabdomyolysis among other
etiologies. Cocaine is only rarely implicated as an etiology of AKI and if it is,
usually the injury is due to ATN or pigment effects. Acute interstitial nephritis
(AIN) caused by cocaine, on the other hand, has only been described in a handful
of cases. AIN is a renal lesion that causes a decline in creatinine clearance and
is characterized by an inflammatory infiltrate in the kidney interstitium and is
most often associated with drug therapy. AIN can also be seen in autoimmune
disorders like systemic lupus erythematosus, Sjogren's syndrome, or sarcoidosis;
or with infections remote to the kidney like Legionella, leptospirosis, and
streptococcal disease. Our case was very similar to the other reported cases of
AIN due to cocaine in that all have occurred in middle-aged African American
males and all have responded to steroids. This case reminds clinicians to
consider AIN in patients with AKI and a history of cocaine abuse.
PMID- 26425623
TI - A Spotty Liver of Pregnancy.
AB - Herpes simplex virus (HSV) hepatitis by definition constitutes disseminated
herpes simplex infection; it is rare, with only approximately 130 cases reported
in the literature. Although HSV hepatitis typically occurs in immunocompromised
hosts, pregnancy-especially the third trimester, has been identified as a risk
factor for its development. This is likely because of the fact that humoral and
cell-mediated immunity decrease throughout pregnancy and nadir in the third
trimester with decreased T-cell counts and altered B/T lymphocyte ratios. Here,
we report on a patient with HSV 2 hepatitis in a previously healthy 27-year-old
woman in her 23rd week of pregnancy. She initially presented with nausea,
vomiting, and abdominal pain and was found to have acute hepatocellular liver
injury and a systemic inflammatory response syndrome. Broad-spectrum antibiotics
and acyclovir were promptly initiated. Liver biopsy, serum DNA polymerase chain
reaction (PCR) as well as a labial ulcer culture and PCR were all positive for
HSV 2. The patient recovered completely; however, her fetus did not survive.
Review of the literature emphasizes that presentation with disseminated HSV
infection typically occurs in the third trimester of pregnancy. This report
emphasizes that abdominal pain combined with fever and hepatic dysfunction in
pregnancy should prompt immediate consideration of the diagnosis of HSV
hepatitis. Furthermore, given the high mortality rate and effective treatment,
empiric treatment with acyclovir should be considered early in all potential
cases.
PMID- 26425625
TI - Cocaine Intoxication and Thyroid Storm: Similarity in Presentation and
Implications for Treatment.
AB - Introduction. Cocaine, a widely used sympathomimetic drug, causes
thermoregulatory and cardiac manifestations that can mimic a life-threatening
thyroid storm. Case. A man presented to the emergency department requesting only
cocaine detoxification. He reported symptoms over the last few years including
weight loss and diarrhea, which he attributed to ongoing cocaine use. On
presentation he had an elevated temperature of 39.4 degrees C and a heart rate up
to 130 beats per minute. Examination revealed the presence of an enlarged,
nontender goiter with bilateral continuous bruits. He was found to have
thyrotoxicosis by labs and was treated for thyroid storm and cocaine intoxication
concurrently. The patient was ultimately diagnosed with Graves' disease and
treated with iodine-131 therapy. Conclusion. Cocaine use should be considered a
possible trigger for thyroid storm. Recognition of thyroid storm is critical
because of the necessity for targeted therapy and the significant mortality
associated with the condition if left untreated.
PMID- 26425624
TI - Anesthetic Considerations for a Patient With Hereditary Hemorrhagic
Telangiectasia (Osler-Weber-Rendu Syndrome) Undergoing a Five-Box Thoracoscopic
Maze Procedure for Atrial Fibrillation.
AB - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic
disorder involving the abnormal communication of vascular structures. HHT
typically presents with recurrent epistaxis and telangiectasis of the nasal and
buccal mucosa, tongue, and lips. More serious manifestations of this disease
include cerebral, pulmonary, gastrointestinal, and hepatic arteriovenous
malformations. This case report details a 55-year-old male with HHT undergoing a
five-box maze procedure for curative treatment of atrial fibrillation. Particular
anesthetic considerations are described to reduce morbidity and mortality in this
patient population.
PMID- 26425626
TI - Methimazole-Induced Goitrogenesis in an Adult Patient With the Syndrome of
Resistance to Thyroid Hormone.
AB - Patients with the syndrome of resistance to thyroid hormone (RTH) have clinical
(tachycardia and anxiety) and biochemical (elevated thyroid hormones level)
features of hyperthyroidism. Based on previous reports in pediatric patients with
the RTH, antithyroid treatment in these patients is not indicated. Clinical and
biochemical sequel of antithyroid therapy in an adult patient with RTH was not
previously reported. A 63-year-old African American female with history of RTH
was treated with a therapy consisting of methimazole 15 mg daily and atenolol.
Methimazole treatment resulted in reduction in thyroid hormone level while the
patient's TSH increased with a peak of 24.88 mIU/L. Having achieved biochemical
euthyroidism, the patient developed thyroid gland enlargement associated with
progressive symptoms of dysphagia and dyspnea. Examination demonstrated globally
enlarged firm thyroid gland with areas of nodularity in both lobes. A computed
tomography of the neck showed enlarged thyroid gland with extension around
bilateral sternocleidomastoid muscles and compression onto the trachea.
Methimazole therapy was discontinued and patient was treated just on atenolol.
Over 12 months following discontinuation of methimazole, the patient experienced
marked clinical and radiographic improvement of the goiter size associated with
TSH reduction to 1.26 mIU/L and modest free thyroxine increase as expected in
RTH. It seems appealing to treat patients with the RTH with antithyroid
medications. However, in these patients decrease in thyroid hormone levels will
stimulate TSH production, which can, in turn, predispose to goiter formation. Our
report supports prior observations in children with RTH that treatment with
methimazole is not indicated in adult patients with RTH.
PMID- 26425627
TI - Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus
Vaccination: A Case Series Seen in General Practice.
AB - Three young women who developed premature ovarian insufficiency following
quadrivalent human papillomavirus (HPV) vaccination presented to a general
practitioner in rural New South Wales, Australia. The unrelated girls were aged
16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to
the onset of ovarian decline. Vaccinations had been administered in different
regions of the state of New South Wales and the 3 girls lived in different towns
in that state. Each had been prescribed the oral contraceptive pill to treat
menstrual cycle abnormalities prior to investigation and diagnosis. Vaccine
research does not present an ovary histology report of tested rats but does
present a testicular histology report. Enduring ovarian capacity and duration of
function following vaccination is unresearched in preclinical studies, clinical
and postlicensure studies. Postmarketing surveillance does not accurately
represent diagnoses in adverse event notifications and can neither represent
unnotified cases nor compare incident statistics with vaccine course
administration rates. The potential significance of a case series of adolescents
with idiopathic premature ovarian insufficiency following HPV vaccination
presenting to a general practice warrants further research. Preservation of
reproductive health is a primary concern in the recipient target group. Since
this group includes all prepubertal and pubertal young women, demonstration of
ongoing, uncompromised safety for the ovary is urgently required. This matter
needs to be resolved for the purposes of population health and public vaccine
confidence.
PMID- 26425628
TI - Ischemic Hepatitis as the Presenting Manifestation of Cardiac Amyloidosis.
AB - An abrupt elevation in aminotransferases without clear etiology may be attributed
to hypoxic hepatitis. Underlying cardiac dysfunction, an important clinical clue,
is often overlooked as a cause of hypoxic hepatitis, and understanding the
interdependence of the heart and liver is crucial in making this diagnosis.
Causes of cardiac dysfunction may include any of many different diagnoses;
infiltrative heart disease is a rare cause of cardiac dysfunction, with
amyloidosis being the most common among this category of pathologies. More
advanced imaging techniques have improved the ability to diagnose infiltrative
heart disease, thus allowing quicker diagnosis of conditions such as amyloidosis.
PMID- 26425629
TI - Two Cases of Transcutaneous Electrical Nerve Stimulation of the Common Peroneal
Nerve Successfully Treating Refractory, Multifactorial Leg Edema.
AB - The treatment of leg edema often involves promoting venous blood flow but can be
difficult in patients with comorbidities that prevent traditional management
strategies such as limb elevation or mechanical compression devices. The geko
device is a self-contained neuromuscular stimulation device that adheres to skin
over the common peroneal nerve and delivers a low-voltage stimulus that activates
the lower-leg musculature resulting in enhanced superficial femoral vein blood
flow and velocity. Here we report 2 cases of multifactorial and refractory leg
edema successfully treated with the geko device over a period of 4 to 16 weeks.
The device also improved pain and chronic wound healing. Although the geko device
is costly, it was well tolerated and may provide another treatment strategy for
resistant leg swelling.
PMID- 26425630
TI - Histological Regression of Giant Cell Tumor of Bone Following RANK Ligand
Inhibition.
AB - Lung metastases are a rare complication of giant cell tumors of bone. We herein
describe an interesting case of histological regression and size reduction of
lung metastases originating from a primary giant cell tumor of bone in response
to the RANK ligand inhibitor denosumab.
PMID- 26425631
TI - Embolic Stroke Diagnosed by Elevated D-Dimer in a Patient With Negative TEE for
Cardioembolic Source.
AB - We report a case of cerebrovascular accident with thromboembolic stroke etiology
in a patient who had atrial flutter and negative transesophageal echocardiography
(TEE) results. The increased D-dimer levels (1877 ng/mL) initiated referral for
magnetic resonance imaging and magnetic resonance angiography of the brain that
showed classic recanalization of an embolic thrombus in the angular branch of the
left middle cerebral distribution. The D-dimer level of this patient was
normalized after 3 months of anticoagulation therapy. Although TEE is considered
the gold standard for evaluation of cardiac source of embolism, exclusion of
intracardiac thrombus with TEE alone does not eliminate the risk of
thromboembolic events. This case highlights the utility of D-dimer as a potential
adjunct in the decision-making process to guide investigation of thromboembolism,
determine subsequent therapy, and hence reduce the risk of embolic stroke
recurrence.
PMID- 26425632
TI - A Case of Sarcoidosis Associated With Anti-Tumor Necrosis Factor Treatment.
AB - Sarcoidosis is a systemic chronic granulomatous disease of unknown etiology. It
predominantly involves the lungs but can affect many organs or tissues in the
body, such as the lymphatic system, skin, eyes, and liver. Typical
histopathological lesions are noncaseating granulomas in the affected organ or
tissue. Indications, type of treatment, and duration of sarcoidosis treatment is
currently debated. Despite studies showing that anti-tumor necrosis factor-alpha
(TNF-alpha) treatment can successfully be used in refractory sarcoidosis, there
are some case reports regarding the development of sarcoidosis with these agents.
There have been reports of 47 anti-TNF-associated cases of sarcoidosis until
2012. The patient is a 54-year-old Caucasian male. During routine examinations of
the patient who had been followed for psoriasis vulgaris for 20 years and who had
been on several anti-TNF regimens thereafter, new pulmonary pathologies due to
sarcoidosis were detected. We present here a case of sarcoidosis that developed
after infliximab treatment and showed obvious radiologic regression with
discontinuation of treatment. During anti-TNF treatment, it should be kept in
mind that autoimmune and granulomatous diseases may develop and particular care
should be given to patient follow-ups.
PMID- 26425633
TI - Cocaine: A Rare Cause of Left-Sided Renal Infarction.
AB - Cocaine abuse is commonly associated with myocardial ischemia, mesenteric
ischemia, and cerebrovascular accidents. Renal infarction is an uncommon
complication of cocaine abuse. Various mechanisms have been postulated for this
cocaine-related injury. There are only 15 cases reported on cocaine-induced renal
infarction. Among the cases with available data, very few cases had left kidney
involvement. We report a case of a 65-year-old African American man with history
of cocaine abuse who presented with left flank pain and had left renal
infarction.
PMID- 26425634
TI - When Feeding Difficulties Are due to Genetics: The Case of Familial Partial 9q
Duplication.
AB - Chromosomal abnormalities may cause growth failure before or since birth. 9q
duplication is reported as a cause of intrauterine growth restriction, mild
dysmporphism, and intellectual disabilities. We report a case of a maternally
inherited 9q21.31q21.33 duplication causing prenatal and postnatal growth
restriction with feeding refusal and mild facial dysmorphisms, prenatally
diagnosed by single-nucleotide polymorphism array analysis. Hypothesis of the
possible pathogenic mechanisms are discussed.
PMID- 26425635
TI - Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing
Multiple Sclerosis.
AB - A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15
months, developed acute lymphoblastic leukemia and died 4 months after immune
ablation and bone marrow allograft, from graft versus host disease. To our
knowledge, this is the first case of acute lymphoblastic leukemia reported in a
patient treated with fingolimod. Although no causal relationship can be
established between fingolimod use and acute lymphoblastic leukemia risk in this
single case, future surveillance for lymphatic cell malignancies in patients
treated with fingolimod appears justified.
PMID- 26425636
TI - CT and MRI Findings of Autoimmune Polymorph Bifocal Pancreatitis Mimicking
Pancreatic Adenocarcinoma: A Case Report and Review of the Literature.
AB - Autoimmune pancreatitis is a rare type of chronic pancreatitis. It is supposed to
be a pancreatic manifestation of an immune-complex modulated systemic disorder.
In contrast, pancreatic adenocarcinoma is the most frequent malignant neoplasm of
the pancreas. Within the rare type of focal autoimmune pancreatitis, only few
presentations with multifocal pancreatic lesions have been described. Herein we
report a case of a 58-year-old patient with autoimmune pancreatitis presenting
with bifocal manifestations of the pancreatic head and tail, mimicking pancreatic
adenocarcinoma clinically, on computed tomography and magnetic resonance imaging.
Typical imaging findings of autoimmune pancreatitis are compared with typical
findings in pancreatic carcinoma. The diagnostic dilemma of differentiating
between both entities is discussed. A review of the present literature regarding
multifocal presence of autoimmune pancreatitis is performed.
PMID- 26425637
TI - Fever-Induced Brugada Syndrome.
AB - Brugada syndrome is increasingly recognized as a cause of sudden cardiac death.
Many of these patients do not get diagnosed due its dynamic and often hidden
nature. We have come a long way in understanding the disease process, and its
electrophysiology appears to be intimately linked with sodium channel mutations
or disorders. The cardiac rhythm in these patients can deteriorate into fatal
ventricular arrhythmias. This makes it important for the clinician to be aware of
the conditions in which arrhythmogenicity of Brugada syndrome is revealed or even
potentiated. We present such an instance where our patient's Brugada syndrome was
unmasked by fever.
PMID- 26425638
TI - Metastatic Adenocarcinoma of Unknown Origin Presenting as Small Bowel
Perforation: A Case Report and Literature Review.
AB - Metastatic malignant tumors that originate from occult primaries are defined as
"cancers of unknown origin." We herein present the case of a 59-year-old man who
presented with small bowel perforation secondary to metastatic adenocarcinoma of
an unknown primary site. Imaging exhibited two pulmonary nodules, neither of
which was dominant, along with mediastinal and retroperitoneal lymphadenopathy.
Immunohistochemical profiling of the small bowel biopsy specimens revealed the
tumor was most likely pulmonary in origin.
PMID- 26425639
TI - Idiopathic Splenic Artery Pseudoaneurysm Rupture as an Uncommon Cause of
Hemorrhagic Shock.
AB - Splenic artery pseudoaneurysms are infrequently encountered but critical to
recognize. Limited literature to date describes associations with pancreatitis,
trauma, and rarely peptic ulcer disease. Hemorrhage and abdominal pain are the
most common manifestations. There is typically overt gastrointestinal blood loss
but bleeding can also extend into the peritoneum, retroperitoneum, adjacent
organs, or even a pseudocyst. Most patients with ruptured splenic artery
pseudoaneurysms present with hemodynamic instability. Here, we describe a patient
recovering from acute illness in the intensive care unit but with otherwise no
obvious risk factors or precipitants for visceral pseudoaneurysm. He presented
with acute onset altered mental status, nausea, and worsening back and abdominal
pain and was found to be in hypovolemic shock. The patient was urgently
stabilized until more detailed imaging could be performed, which ultimately
revealed the source of blood loss and explained his rapid decompensation. He was
successfully treated with arterial coiling and embolization. Thus, we herein
emphasize the importance of prompt recognition of hemorrhagic shock and of
aggressive hemodynamic stabilization, as well as a focused diagnostic approach to
this problem with specific treatment for splenic artery pseudoaneurysm. Finally,
we recommend that multidisciplinary management should be the standard approach in
all patients with splenic artery pseudoaneurysm.
PMID- 26425640
TI - Double Cystic Duct in a Septated Gallbladder.
AB - Double cystic duct in a single gallbladder is one of the least common variances
encountered in the biliary system. This article presents a 54-year-old man who
had a septated gallbladder with 2 separate cystic ducts. With intraoperative
cholangiogram, he had successful laparoscopic cholecystectomy without any ductal
injuries or complications.
PMID- 26425642
TI - Metastasizing Bronchopulmonary Leiomyosarcoma.
AB - An otherwise healthy 55-year-old female, nonsmoker, was seen in pulmonary
consultation for progressively worsening shortness of breath. She had undergone a
complete hysterectomy 7 years prior for bleeding leiomyomas. On presentation, her
initial chest X-ray showed a large right-sided pleural effusion with multiple
pulmonary nodules. Two thoracenteses failed to reveal any cytologic
abnormalities. Bronchoscopy revealed smooth, round, endobronchial lesions.
Histologic examination showed features consistent with leiomyosarcoma. We present
a rare case of a patient that initially had possible leiomyomas of the uterus
surgically removed and years later presented with bronchopulmonary
leiomyosarcoma.
PMID- 26425641
TI - Spilt Milk: An Unusual Cause of Bilateral Chylothorax.
AB - We report a case of bilateral chylothorax without evidence of chylous fistula in
a 62-year-old man following total laryngectomy and bilateral selective neck
dissection for laryngeal cancer. Chylous fistulae, a well-known complication of
neck dissection, occurs following 1% to 2% of these surgeries. On rare occasions,
the chyle leak may communicate with the pleural space, resulting in chylothorax.
This is a rare but potentially life-threatening complication. Bilateral
chylothorax following neck dissection is even rarer, with less than 25 cases
reported in the literature. Early diagnosis is essential to prevent
complications. Physicians should have a high index of suspicion, especially when
the postoperative effusions do not respond to diuretics. Though no evidence-based
treatment guidelines exist, expert opinion recommends conservative management as
first-line therapy. Our patient was effectively treated by conservative
management. We postulate a mechanism whereby bilateral chylothorax occurred in
our patient without a chylous fistula.
PMID- 26425644
TI - Unusually Located Stroke After Chemotherapy in Testicular Germ Cell Tumors.
AB - Testicular cancer is a type of malignancy that affects young adults and has high
rates of cure; however, as any malignancy, it is associated with an increased
risk of ischemic or hemorrhagic cerebrovascular disease, given the systemic tumor
effects or side effects of chemotherapy, which in turn increases morbidity,
functional impairment, and additional risk of early death.
PMID- 26425643
TI - Vocal Hoarseness and a Subglottic Mass: An Uncommon Diagnosis for a Common
Complaint.
AB - We report a patient with tracheopathia osteoplastica (TPO), a rare or perhaps
underrecognized disorder, detected in approximately 1 in every 2000 to 5000
patients who undergo bronchoscopy. TPO is marked by proliferation of bony and
cartilaginous spurs leading to airway stenosis. Multiple submucosal cartilaginous
and osseous nodules can develop in the respiratory tract and may involve the
entire trachea and mainstem bronchi. Symptoms may range from a completely silent
condition to life-threatening respiratory failure and diagnosis is made based on
radiological and bronchoscopic findings. Although the etiology has not been
established, TPO can be familial and is sometimes associated with chronic
inflammation, such as seen with rheumatic diseases. This case highlights the need
for understanding TPO so that it can be differentiated from potentially serious
conditions such as necrotizing granulomatous diseases, invasive infections, and
cancer.
PMID- 26425645
TI - Acute Pancreatitis Induced by Methimazole in a Patient With Subclinical
Hyperthyroidism.
AB - We report here a unique case of methimazole (MMI)-induced pancreatitis. To our
knowledge, this is the sixth case reported in the literature and the first
diagnosed in a patient with toxic multinodular goiter. A 51-year-old Caucasian
female with a history of benign multinodular goiter and subclinical
hyperthyroidism was started on MMI 10 mg orally daily. Three weeks later, she
developed sharp epigastric pain, diarrhea, lack of appetite, and fever. Her
lipase was elevated 5 times the upper limit of normal, consistent with acute
pancreatitis. There was no history of hypertriglyceridemia, or alcohol abuse.
Abdominal computed tomography was consistent with acute uncomplicated
pancreatitis, without evidence of gallstones or tumors. MMI was discontinued, and
her hyperthyroid symptoms were managed with propranolol. Her acute episode of
pancreatitis quickly resolved clinically and biochemically. One year later, she
redeveloped mild clinical symptoms of hyperthyroidism with biochemical evidence
of subclinical hyperthyroidism. MMI 10 mg orally daily was restarted. Five days
later, she experienced progressive abdominal discomfort. Her lipase was elevated
12 times the upper limit of normal, and the abdominal computed tomography was
again compatible with acute uncomplicated pancreatitis. MMI was again
discontinued, which was followed by rapid resolution of her pancreatitis. The
patient is currently considering undergoing definitive therapy with radioactive
iodine ablation. Our case as well as previous case reports in the literature
should raise awareness about the possibility of pancreatitis in subjects treated
with MMI in the presence of suggestive symptoms. If the diagnosis is confirmed by
elevated pancreatic enzymes, the drug should be discontinued.
PMID- 26425646
TI - Gas6/Axl in arginine-starvation therapy.
PMID- 26425647
TI - betaNp63 controls cellular redox status.
PMID- 26425648
TI - miR-25, integrin and cancer invasiveness.
PMID- 26425649
TI - BMI1, ATM and DDR.
PMID- 26425651
TI - The many-faced KSR1: a tumor suppressor in breast cancer.
PMID- 26425650
TI - Immunosuppression via Tenascin-C.
PMID- 26425652
TI - Targeting ncRNAs in the 3q26.2 amplicon.
PMID- 26425653
TI - ATP, a double-edged sword in cancer.
PMID- 26425654
TI - Cell hierarchies in colorectal cancer: focus on APC and BRAF.
PMID- 26425655
TI - NK cell modulation by JAK inhibition.
PMID- 26425656
TI - Cell-ECM interactions control DDR.
PMID- 26425657
TI - Right on TARGET: glutamine metabolism in cancer.
AB - Recent studies highlight the importance of glutamine metabolism in metabolic
reprogramming, which underlies cancer cell addiction to glutamine. Examples for
the dependence on glutamine metabolism are seen across different tumor types as
during different phases of cancer development, progression and response to
therapy. In this perspective, we assess the possibility of targeting glutamine
metabolism as a therapeutic modality for cancer.
PMID- 26425659
TI - A novel telomerase substrate precursor rapidly induces telomere dysfunction in
telomerase positive cancer cells but not telomerase silent normal cells.
AB - Although telomerase is an almost universal target for cancer therapy, there has
been no effective telomerase targeted inhibitor that has progressed to late stage
human clinical trials. Recently, we reported that a telomerase-mediated telomere
disrupting compound, 6-thio-2'-deoxyguanosine (6-thio-dG), was very effective at
targeting telomerase positive cancer cells while sparing telomerase silent normal
cells. 6-thio-dG, a nucleoside analogue of the already-approved drug 6
thioguanine, is incorporated into telomeres by telomerase, resulting in
disruption of the telomere-protecting shelterin complex. This disruption leads to
Telomere dysfunction-Induced Foci (TIFs) formation and rapid cell death for the
vast majority of cancer cells. Since most chemotherapies eventually fail due to
drug acquired resistance, novel drugs such as 6-thio-dG, as a single first line
agent or in the maintenance setting, may represent an effective new treatment for
cancer patients.
PMID- 26425658
TI - How to target small cell lung cancer.
AB - Small cell lung cancer (SCLC) is a highly malignant disease with dismal
prognosis. Although great progress has been made in investigating genetic
aberrations and putative drivers of this tumor entity, the mechanisms of rapid
dissemination and acquisition of drug resistance are not clear. The majority of
SCLC cases are characterized by inactivation of the tumor suppressors p53 and
retinoblastoma (Rb) and, therefore, interchangeable drivers will be difficult to
target successfully. Access to pure cultures of SCLC circulating tumor cells
(CTCs) and study of their tumor biology has revealed a number of new potential
targets. Most important, expression of chitinase-3-like-1/YKL-40 (CHI3L1) which
controls expression of vascular epithelial growth factor (VEGF) and matrix
metalloproteinase-9 (MMP9) was newly described in these cells. The process
switching CHI3L1-negative SCLC cells to CHI3L1-positive CTCs seems to be
associated with cytokines released by inflammatory immune cells. Furthermore,
these CTCs were found to promote monocyte-macrophage differentiation, most likely
of the M2 tumor-promoting type, recently described to express PD-1 immune
checkpoint antigen in SCLC. In conclusion, dissemination of SCLC seems to be
linked to conversion of regular tumor cells to highly invasive CHI3L1-positive
CTCs, which are protected by immune system suppression. Besides the classical
targets VEGF, MMP-9 and PD-1, CHI3L1 constitutes a new possibly drugable molecule
to retard down dissemination of SCLC cells, which may be similarly relevant for
glioblastoma and other tumor entities.
PMID- 26425660
TI - Doxycycline and therapeutic targeting of the DNA damage response in cancer cells:
old drug, new purpose.
AB - There is a small proportion of cells within a tumour with self-renewing
properties, which is resistant to conventional therapy, and is responsible for
tumour initiation, maintenance and metastasis. These cells are known as cancer
stem cells (CSCs) or tumour-initiating cells (TICs) [1]. Recent publications
identify several antibiotics, such as salinomycin or doxycycline, as selective
CSCs inhibitors [2-4]. However, the mechanisms of action of these antibiotics on
CSCs are not fully understood.
PMID- 26425661
TI - PRMT5-dependent p53 escape in tumorigenesis.
AB - Extensive studies have characterized mutational disruption of p53 signaling in
human cancers. However, the mechanism for bypass of p53 function in tumors
retaining wild-type p53 has remained ambiguous. Recent studies suggest that
PRMT5, which is frequently elevated in human cancers, cooperates with oncogenic
cyclin D1 and leaves marks on p53 by way of arginine methylation, promoting the
bypass of wild-type p53, and in doing so, evade apoptosis.
PMID- 26425664
TI - Dataset from the global phosphoproteomic mapping of early mitotic exit in human
cells.
AB - The presence or absence of a phosphorylation on a substrate at any particular
point in time is a functional readout of the balance in activity between the
regulatory kinase and the counteracting phosphatase. Understanding how stable or
short-lived a phosphorylation site is required for fully appreciating the
biological consequences of the phosphorylation. Our current understanding of
kinases and their substrates is well established; however, the role phosphatases
play is less understood. Therefore, we utilized a phosphatase dependent model of
mitotic exit to identify potential substrates that are preferentially
dephosphorylated. Using this method, we identified >16,000 phosphosites on >3300
unique proteins, and quantified the temporal phosphorylation changes that occur
during early mitotic exit (McCloy et al., 2015 [1]). Furthermore, we annotated
the majority of these phosphorylation sites with a high confidence upstream
kinase using published, motif and prediction based methods. The results from this
study have been deposited into the ProteomeXchange repository with identifier
PXD001559. Here we provide additional analysis of this dataset; for each of the
major mitotic kinases we identified motifs that correlated strongly with
phosphorylation status. These motifs could be used to predict the stability of
phosphorylated residues in proteins of interest, and help infer potential
functional roles for uncharacterized phosphorylations. In addition, we provide
validation at the single cell level that serine residues phosphorylated by Cdk
are stable during phosphatase dependent mitotic exit. In summary, this unique
dataset contains information on the temporal mitotic stability of thousands of
phosphorylation sites regulated by dozens of kinases, and information on the
potential preference that phosphatases have at both the protein and individual
phosphosite level. The compellation of this data provides an invaluable resource
for the wider research community.
PMID- 26425662
TI - Mcl-1 protects prostate cancer cells from cell death mediated by chemotherapy
induced DNA damage.
AB - The anti-apoptotic protein Mcl-1 is highly expressed in castration-resistant
prostate cancer (CRPC), resulting in resistance to apoptosis and association with
poor prognosis. Although predominantly localized in the cytoplasm, there is
evidence that Mcl-1 exhibits nuclear localization where it is thought to protect
against DNA damage-induced cell death. The role of Mcl-1 in mediating resistance
to chemotherapy-induced DNA damage in prostate cancer (PCa) is not known. We show
in human PCa cell lines and in TRAMP, a transgenic mouse model of PCa, that the
combination of the antimitotic agent ENMD-1198 (analog of 2-methoxyestradiol)
with betulinic acid (BA, increases proteotoxic stress) targets Mcl-1 by
increasing its proteasomal degradation, resulting in increased gammaH2AX (DNA
damage) and apoptotic/necrotic cell death. Knockdown of Mcl-1 in CRPC cells leads
to elevated gammaH2AX, DNA strand breaks, and cell death after treatment with
1198 + BA- or doxorubicin. Additional knockdowns in PC3 cells suggests that
cytoplasmic Mcl-1 protects against DNA damage by blocking the mitochondrial
release of apoptosis-inducing factor and thereby preventing its nuclear
translocation and subsequent interaction with the cyclophilin A endonuclease.
Overall, our results suggest that chemotherapeutic agents that target Mcl-1 will
promote cell death in response to DNA damage, particularly in CRPC.
PMID- 26425665
TI - SILAC-based quantification of changes in protein tyrosine phosphorylation induced
by Interleukin-2 (IL-2) and IL-15 in T-lymphocytes.
AB - This data article presents the first large-scale quantitative phosphoproteomics
dataset generated to decipher the signaling networks initiated by IL-2 and IL-15
in T-lymphocytes. Data was collected by combining immunoprecipitation of tyrosine
phosphorylated proteins and TiO2-based phosphopeptide enrichment with SILAC-based
quantitative mass spectrometry. We report all the proteins and phosphotyrosine
containing peptides identified and quantified in IL-2- and IL-15-stimulated T
lymphocytes. The gene ontology analysis of IL-2 and IL-15 effector proteins
detected in the present work is also included. The data supplied in this article
is related to the research work entitled "Simultaneous dissection and comparison
of IL-2 and IL-15 signaling pathways by global quantitative phosphoproteomics"
[1]. All mass spectrometry data have been deposited in the ProteomeXchange with
the identifier PXD001129.
PMID- 26425663
TI - Quantitative evaluation of cell death response in vitro and in vivo using
conventional-frequency ultrasound.
AB - Previous studies using high-frequency ultrasound have suggested that
radiofrequency (RF) spectral analysis can be used to quantify changes in cell
morphology to detect cell death response to therapy non-invasively. The study
here investigated this at conventional-frequencies, frequently used in clinical
settings. Spectral analysis was performed using ultrasound RF data collected with
a clinical ultrasound platform. Acute myeloid leukemia (AML-5) cells were exposed
to cisplatinum for 0-72 hours in vitro and prepared for ultrasound data
collection. Preclinical in vivo experiments were also performed on AML-5 tumour
bearing mice receiving chemotherapy. The mid-band fit (MBF) spectral parameter
demonstrated an increase of 4.4 +/- 1.5 dBr for in vitro samples assessed 48
hours after treatment, a statistically significant change (p < 0.05) compared to
control. Further, in vitro concentration-based analysis of a mixture of apoptotic
and untreated cells indicated a mean change of 10.9 +/- 2.4 dBr in MBF between 0%
and 40% apoptotic cell mixtures. Similar effects were reproduced in vivo with an
increase of 4.6 +/- 0.3 dBr in MBF compared to control, for tumours with
considerable apoptotic areas within histological samples. The alterations in the
size of cells and nuclei corresponded well with changes measured in the
quantitative ultrasound (QUS) parameters.
PMID- 26425666
TI - Reciprocal repression between Fgf8 and miR-133 regulates cardiac induction
through Bmp2 signaling.
AB - This data article contains complementary figures and results related to the
research article entitled "Negative Fgf8-Bmp2 feed-back is controlled by miR-130
during early cardiac specification" [15], which reveals what specific role miR
130 plays during the cardiac induction process. This study evidenced miR-130 a
putative microRNA that targets Erk1/2 (Mapk1) 3'UTR- as a necessary linkage in
the control of Fgf8 signaling, mediated by Bmp2. Thus, miR-130 regulates a
negative Fgf8-Bmp2 feed-back loop responsible to achieve early cardiac
specification. A significant aspect supporting our conclusions is given by the
expression pattern of miR-130 during early cardiac specification, as well as by
those results obtained after the designed experimental procedures. The data
presented here reveal that miR-133 is also expressed within the precardiac areas
during early cardiogenesis, pattern which is comparable to that of FGFR1,
receptor involved in the Fgf8/ERK signaling pathway. Interestingly, our miR-133
overexpression experiments resulted in a decrease of Fgf8 expression, whereas we
observed an increase of Bmp2 and subsequently of cardiac specific markers Nkx-2.5
and Gata4. Additionally, our loss-of-function experiments -through Fgf8 siRNA
electroporation- showed an increase of miR-133 expression. Finally, after our
Bmp2 experiments, we observed that miR-133 is upstream-regulated by Bmp2. All
those results suggest that miR-133 also constitutes a crucial linkage in the
crosstalk between Fgf8 and Bmp2 signaling by regulating the Fgf8/ERK pathway
during cardiac induction.
PMID- 26425667
TI - Dissipated power and induced velocity fields data of a micro single dielectric
barrier discharge plasma actuator for active flow control.
AB - In recent years, single dielectric barrier discharge (SDBD) plasma actuators have
gained great interest among all the active flow control devices typically
employed in aerospace and turbomachinery applications [1,2]. Compared with the
macro SDBDs, the micro single dielectric barrier discharge (MSDBD) actuators
showed a higher efficiency in conversion of input electrical power to delivered
mechanical power [3,4]. This article provides data regarding the performances of
a MSDBD plasma actuator [5,6]. The power dissipation values [5] and the
experimental and numerical induced velocity fields [6] are provided. The present
data support and enrich the research article entitled "Optimization of micro
single dielectric barrier discharge plasma actuator models based on experimental
velocity and body force fields" by Pescini et al. [6].
PMID- 26425668
TI - A predictive toxicogenomics signature to classify genotoxic versus non-genotoxic
chemicals in human TK6 cells.
AB - Genotoxicity testing is a critical component of chemical assessment. The use of
integrated approaches in genetic toxicology, including the incorporation of gene
expression data to determine the DNA damage response pathways involved in
response, is becoming more common. In companion papers previously published in
Environmental and Molecular Mutagenesis, Li et al. (2015) [6] developed a dose
optimization protocol that was based on evaluating expression changes in several
well-characterized stress-response genes using quantitative real-time PCR in
human lymphoblastoid TK6 cells in culture. This optimization approach was applied
to the analysis of TK6 cells exposed to one of 14 genotoxic or 14 non-genotoxic
agents, with sampling 4 h post-exposure. Microarray-based transcriptomic analyses
were then used to develop a classifier for genotoxicity using the nearest
shrunken centroids method. A panel of 65 genes was identified that could
accurately classify toxicants as genotoxic or non-genotoxic. In Buick et al.
(2015) [1], the utility of the biomarker for chemicals that require metabolic
activation was evaluated. In this study, TK6 cells were exposed to increasing
doses of four chemicals (two genotoxic that require metabolic activation and two
non-genotoxic chemicals) in the presence of rat liver S9 to demonstrate that S9
does not impair the ability to classify genotoxicity using this genomic biomarker
in TK6cells.
PMID- 26425669
TI - Getting Healthier Through Microbiome Makeover.
PMID- 26425670
TI - Flibanserin for Low Sexual Desire in Women: A Molecule From Bench to Bed?
PMID- 26425671
TI - Neural Stem Cell Carriers for the Treatment of Glioblastoma Multiforme.
PMID- 26425672
TI - New Brain Lymphatic Vessels Drain Old Concepts.
PMID- 26425673
TI - Is it Possible to Predict Benefit from 5FU Adjuvant Therapy in Stage III Colon
Cancer Patients?
PMID- 26425674
TI - Deciphering Crosstalk Circuits in Non-small Cell Lung Cancers with an Increasing
Interval Length of Low Dose CT Screening.
PMID- 26425675
TI - Surrogate Prognostic Biomarkers in OSCC: The Paradigm of PA28gamma
Overexpression.
PMID- 26425676
TI - Suppress for Success: A JAK Inhibitor for Adjunct Therapy of Tuberculosis.
PMID- 26425677
TI - How Much HIV is Alive? The Challenge of Measuring Replication Competent HIV for
HIV Cure Research.
PMID- 26425678
TI - Dormancy antigens as biomarkers of latent tuberculosis infection.
PMID- 26425679
TI - Unpacking Vaccine Hesitancy Among Healthcare Providers.
PMID- 26425680
TI - Is Psychosis a Disorder of XY Epigenetics?
PMID- 26425681
TI - The Importance of Measuring Multi-level Risk and Illness Progression Markers in
High-risk Youth From Well-characterized Bipolar Parents.
PMID- 26425682
TI - DNA methylation signatures in circulating cell-free DNA for the monitoring of at
risk populations progressing to lung cancer.
PMID- 26425683
TI - Disappearing acts of ADAMTS13.
PMID- 26425684
TI - How can clinical research help our understanding of trastuzumab-related
cardiotoxicity?
PMID- 26425685
TI - Predicting Risk at the End of the End: Telomere G-tail as a Biomarker.
PMID- 26425686
TI - You Lose Some, You Win Some: Weight Loss Induces Microbiota and Metabolite
Shifts.
PMID- 26425687
TI - Inhibition of de novo Palmitate Synthesis by Fatty Acid Synthase Induces
Apoptosis in Tumor Cells by Remodeling Cell Membranes, Inhibiting Signaling
Pathways, and Reprogramming Gene Expression.
AB - Inhibition of de novo palmitate synthesis via fatty acid synthase (FASN)
inhibition provides an unproven approach to cancer therapy with a strong
biological rationale. FASN expression increases with tumor progression and
associates with chemoresistance, tumor metastasis, and diminished patient
survival in numerous tumor types. TVB-3166, an orally-available, reversible,
potent, and selective FASN inhibitor induces apoptosis, inhibits anchorage
independent cell growth under lipid-rich conditions, and inhibits in-vivo
xenograft tumor growth. Dose-dependent effects are observed between 20-200 nM TVB
3166, which agrees with the IC50 in biochemical FASN and cellular palmitate
synthesis assays. Mechanistic studies show that FASN inhibition disrupts lipid
raft architecture, inhibits biological pathways such as lipid biosynthesis, PI3K
AKT-mTOR and beta-catenin signal transduction, and inhibits expression of
oncogenic effectors such as c-Myc; effects that are tumor-cell specific. Our
results demonstrate that FASN inhibition has anti-tumor activities in
biologically diverse preclinical tumor models and provide mechanistic and
pharmacologic evidence that FASN inhibition presents a promising therapeutic
strategy for treating a variety of cancers, including those expressing mutant K
Ras, ErbB2, c-Met, and PTEN. The reported findings inform ongoing studies to link
mechanisms of action with defined tumor types and advance the discovery of
biomarkers supporting development of FASN inhibitors as cancer therapeutics.
RESEARCH IN CONTEXT: Fatty acid synthase (FASN) is a vital enzyme in tumor cell
biology; the over-expression of FASN is associated with diminished patient
prognosis and resistance to many cancer therapies. Our data demonstrate that
selective and potent FASN inhibition with TVB-3166 leads to selective death of
tumor cells, without significant effect on normal cells, and inhibits in vivo
xenograft tumor growth at well-tolerated doses. Candidate biomarkers for
selecting tumors highly sensitive to FASN inhibition are identified. These
preclinical data provide mechanistic and pharmacologic evidence that FASN
inhibition presents a promising therapeutic strategy for treating a variety of
cancers.
PMID- 26425688
TI - TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in
Stage III Colon Cancer Patients.
AB - We investigated the hypothesis that the varying treatment efficacy of adjuvant 5
fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational
status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant
5FU was studied in stage III colon cancer patients. Tumor material of 70% of
these patients (389/572) was available for analysis of the biomarker TP53 using a
TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months.
TP53 mutation frequency was 33%. A significant interaction between TP53 status,
outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53
wildtype patients had significantly better overall survival than TP53 mutated
(81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344-3.378; P
= 0.0010). In the N2 category, the TP53 status did not affect survival (P =
0.4992). In TP53 wildtype patients, the prognostic significance of N category was
significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of
N1 and N2 patients overlapped and nodal category was no longer prognostic. The
biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer
patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no
effect.
PMID- 26425689
TI - Gene Signatures Stratify Computed Tomography Screening Detected Lung Cancer in
High-Risk Populations.
AB - BACKGROUND: Although screening programmes of smokers have detected resectable
early lung cancers more frequently than expected, their efficacy in reducing
mortality remains debatable. To elucidate the biological features of computed
tomography (CT) screening detected lung cancer, we examined the mRNA signatures
on tumours according to the year of detection, stage and survival. METHODS: Gene
expression profiles were analysed on 28 patients (INT-IEO training cohort) and 24
patients of Multicentre Italian Lung Detection (MILD validation cohort). The gene
signatures generated from the training set were validated on the MILD set and a
public deposited DNA microarray data set (GSE11969). Expression of selected genes
and proteins was validated by real-time RT-PCR and immunohistochemistry. Enriched
core pathway and pathway networks were explored by GeneSpring GX10. FINDINGS: A
239-gene signature was identified according to the year of tumour detection in
the training INT-IEO set and correlated with the patients' outcomes. These
signatures divided the MILD patients into two distinct survival groups
independently of tumour stage, size, histopathological type and screening year.
The signatures can also predict survival in the clinically detected cancers
(GSE11969). Pathway analyses revealed tumours detected in later years enrichment
of the PI3K/PTEN/AKT pathway, with up-regulation of PDPK1, ITGB1 and down
regulation of FOXO1A. Analysis of normal lung tissue from INT-IEO cohort produced
signatures distinguishing patients with early from late detected tumours.
INTERPRETATION: The distinct pattern of "indolent" and "aggressive" tumour exists
in CT-screening detected lung cancer according to the gene expression profiles.
The early development of an aggressive phenotype may account for the lack of
mortality reduction by screening observed in some cohorts.
PMID- 26425690
TI - Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell
Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With
Predictive Value.
AB - Lung cancer is the most frequent cause of cancer-related death world-wide.
Radiotherapy alone or in conjunction with chemotherapy is the standard treatment
for locally advanced non-small cell lung cancer (NSCLC). Currently there is no
predictive marker with clinical utility to guide treatment decisions in NSCLC
patients undergoing radiotherapy. Identification of such markers would allow
treatment options to be considered for more effective therapy. To enable the
identification of appropriate protein biomarkers, plasma samples were collected
from patients with non-small cell lung cancer before and during radiotherapy for
longitudinal comparison following a protocol that carries sufficient power for
effective discovery proteomics. Plasma samples from patients pre- and during
radiotherapy who had survived > 18 mo were compared to the same time points from
patients who survived < 14 mo using an 8 channel isobaric tagging tandem mass
spectrometry discovery proteomics platform. Over 650 proteins were detected and
relatively quantified. Proteins which showed a change during radiotherapy were
selected for validation using an orthogonal antibody-based approach. Two of these
proteins were verified in a separate patient cohort: values of CRP and LRG1
combined gave a highly significant indication of extended survival post one week
of radiotherapy treatment.
PMID- 26425691
TI - Associations between proteasomal activator PA28gamma and outcome of oral squamous
cell carcinoma: Evidence from cohort studies and functional analyses.
AB - BACKGROUND: PA28gamma was suggested to play a role in malignant progression. This
paper aimed to investigate the association between PA28gamma and the prognosis of
oral squamous cell carcinoma (OSCC) in cohort studies. METHODS: The PA28gamma
expression level was assessed by immunohistochemistry in a total of 368 OSCC
patients from three independent cohorts. The Cox proportional hazards regression
model was used to determine multivariate hazard ratios for Overall Survival (OS).
Model discrimination was measured using C Statistic. Additionally, OS was
analyzed in Head Neck Squamous Cell Carcinoma (HNSCC) patients from The Cancer
Genome Atlas (TCGA) data set. Functional analyses were conducted both in-vitro
and in-vivo. FINDINGS: The median follow-up times of patients in the three
studies were 60, 52, and 51 months. High expression of PA28gamma was identified
in tumors from 179 of 368 patients (48.6%). Compared with low expression, high
expression of PA28gamma was strongly associated with worse OS, with relative
risks of 5.14 (95% CI, 2.51-10.5; P < 0.001), 2.82 (95% CI, 1.73-4.61; P <
0.001), and 3.85 (95% CI, 1.59-9.37; P = 0.003). PA28gamma expression was also
associated with disease-free survival in all three cohorts (P < 0.005). These
findings are consistent with TCGA HNSCC data (P < 0.006). The prediction of all
cause mortality was significantly improved when PA28gamma was added to the
traditional clinical factors (Model 3, C statistic value: 0.78 VS 0.73, P =
0.016). In functional analyses, we found that PA28gamma silencing dramatically
inhibited the growth, proliferation and mobility of OSCC cells in vitro and
reduced tumor growth and angiogenesis in tumor-bearing mice. INTERPRETATION:
PA28gamma overexpression is associated with adverse prognosis in patients with
OSCC. The aberrant expression of PA28gamma may contribute to the pathogenesis and
progression of OSCC. RESEARCH IN CONTEXT: OSCC is one of the most common HNSCC,
which have a high lethally rate. However, few prognostic markers have been
applied in the clinical practice. We found that PA28gamma in OSCC tumor tissues
were significantly high expression than those in normal tissues. As the results
of the three cohorts from two independent research centers and from an additional
validation cohort from a US population in the TCGA dataset, we demonstrate
PA28gamma is a good predictor of the risk of death in OSCC. Meanwhile, we
demonstrate PA28gamma have a potential role in OSCC tumorigenesis.
PMID- 26425692
TI - Reverse Engineering of Vaccine Antigens Using High Throughput Sequencing-enhanced
mRNA Display.
AB - Vaccine reverse engineering is emerging as an important approach to vaccine
antigen identification, recently focusing mainly on structural characterization
of interactions between neutralizing monoclonal antibodies (mAbs) and antigens.
Using mAbs that bind unknown antigen structures, we sought to probe the intrinsic
features of antibody antigen-binding sites with a high complexity peptide
library, aiming to identify conformationally optimized mimotope antigens that
capture mAb-specific epitopes. Using a high throughput sequencing-enhanced
messenger ribonucleic acid (mRNA) display approach, we identified high affinity
binding peptides for a hepatitis C virus neutralizing mAb. Immunization with the
selected peptides induced neutralizing activity similar to that of the original
mAb. Antibodies elicited by the most commonly selected peptides were
predominantly against specific epitopes. Thus, using mRNA display to interrogate
mAbs permits high resolution identification of functional peptide antigens that
direct targeted immune responses, supporting its use in vaccine reverse
engineering for pathogens against which potent neutralizing mAbs are available.
RESEARCH IN CONTEXT: We used a large number of randomly produced small proteins
("peptides") to identify peptides containing specific protein sequences that bind
efficiently to an antibody that can prevent hepatitis C virus infection in cell
culture. After the identified peptides were injected into mice, the mice produced
their own antibodies with characteristics similar to the original antibody. This
approach can provide previously unavailable information about antibody binding
and could also be useful in developing new vaccines.
PMID- 26425693
TI - Efficacy of Adjunctive Tofacitinib Therapy in Mouse Models of Tuberculosis.
AB - The global tuberculosis (TB) epidemic and the spread of multi- and extensively
drug resistant strains of Mycobacterium tuberculosis (M.tb) have been fueled by
low adherence to following lengthy treatment protocols, and the rapid spread of
HIV (Human Immunodeficiency Virus). Persistence of the infection in
immunocompetent individuals follows from the ability of M.tb to subvert host
immune responses in favor of survival within macrophages. Alternative host
directed strategies are therefore being currently sought to improve treatment
efficacy and duration. In this study, we evaluated tofacitinib, a new oral Janus
kinase (JAK) blocker with anti-inflammatory properties, in shortening
tuberculosis treatment. BALB/c mice, which are immunocompetent, showed
acceleration of M.tb clearance achieving apparent sterilization after 16 weeks of
adjunctive tofacitinib therapy at average exposures higher than recommended in
humans, while mice receiving standard treatment alone did not achieve clearance
until 24 weeks. True sterilization with tofacitinib was not achieved until five
months. C3HeB/FeJ mice, which show reduced pro-inflammatory cytokines during M.tb
infection, did not show improved clearance with adjunctive tofacitinib therapy,
indicating that the nature of granulomatous lesions and host immunity may
influence responsiveness to tofacitinib. Our findings suggest that the JAK
pathway could be explored further for host-directed therapy in immunocompetent
individuals.
PMID- 26425694
TI - A Novel Assay to Measure the Magnitude of the Inducible Viral Reservoir in HIV
infected Individuals.
AB - BACKGROUND: Quantifying latently infected cells is critical to evaluate the
efficacy of therapeutic strategies aimed at reducing the size of the long-lived
viral reservoir, but the low frequency of these cells makes this very
challenging. METHODS: We developed TILDA (Tat/rev Induced Limiting Dilution
Assay) to measure the frequency of cells with inducible multiply-spliced HIV RNA,
as these transcripts are usually absent in latently infected cells but induced
upon viral reactivation. TILDA requires less than a million cells, does not
require RNA extraction and can be completed in two days. FINDINGS: In suppressed
individuals on ART, we found the median frequency of latently infected CD4 + T
cells as estimated by TILDA to be 24 cells/million, which was 48 times more than
the frequency measured by the quantitative viral outgrowth assay, and 6-27 times
less than the frequencies of cells harbouring viral DNA measured by PCR-based
assays. TILDA measurements strongly correlated with most HIV DNA assays. The size
of the latent reservoir measured by TILDA was lower in subjects who initiated ART
during the early compared to late stage of infection (p = 0.011). In untreated
HIV disease, the frequency of CD4 + cells carrying latent but inducible HIV
largely exceeded the frequency of actively producing cells, demonstrating that
the majority of infected cells are transcriptionally silent even in the absence
of ART. INTERPRETATIONS: Our results suggest that TILDA is a reproducible and
sensitive approach to measure the frequency of productively and latently infected
cells in clinical settings. We demonstrate that the latent reservoir represents a
substantial fraction of all infected cells prior to ART initiation. RESEARCH IN
CONTEXT: In this manuscript, we describe the development of a novel assay that
measures the magnitude of the latent HIV reservoir, the main barrier to HIV
eradication. This novel assay, termed TILDA for Tat/rev Induced Limiting Dilution
Assay, requires only 10 ml of blood, does not necessitate extraction of viral
nucleic acids, is highly reproducible, covers a wide dynamic range of reservoir
sizes and can be completed in two days. As such, TILDA may represent an
alternative to existing assays used to evaluate the efficacy of therapeutic
strategies aimed at reducing the size of the latent HIV reservoir.
PMID- 26425696
TI - Vaccine Hesitancy Among General Practitioners and Its Determinants During
Controversies: A National Cross-sectional Survey in France.
AB - BACKGROUND: This study aimed to assess: 1) vaccine hesitancy (VH) prevalence
among French general practitioners (GPs) through the frequency of their vaccine
recommendations, and 2) the determinants of these recommendations. METHODS: Cross
sectional observational study in 2014 nested in a national panel of 1712 randomly
selected GPs in private practice in France. We constructed a score of self
reported recommendation frequency for 6 specific vaccines to target populations.
RESULTS: 16% to 43% of GPs sometimes or never recommended at least one specific
vaccine to their target patients. Multivariable logistic regressions of the
dichotomized score showed that GPs recommended vaccines frequently when they felt
comfortable explaining their benefits and risks to patients (OR = 1.87; 1.35
2.59), or trusted official sources of information highly (OR = 1.40; 1.01-1.93).
They recommended vaccines infrequently when they considered that adverse effects
were likely (OR = 0.71; 0.52-0.96) or doubted the vaccine's utility (OR = 0.21;
0.15-0.29). INTERPRETATION: Our findings show that after repeated vaccine
controversies in France, some VH exists among French GPs, whose recommendation
behaviors depend on their trust in authorities, their perception of the utility
and risks of vaccines, and their comfort in explaining them. Further research is
needed to confirm these results among health care workers in other countries.
PMID- 26425695
TI - A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected
Bacillus Calmette-Guerin-vaccinated Individuals.
AB - IFN-gamma release assays (IGRAs) are better indicators of Mycobacterium
tuberculosis infection than the tuberculin skin test (TST) in Bacillus Calmette
Guerin (BCG)-vaccinated populations. However, IGRAs do not discriminate active
and latent infections (LTBI) and no gold standard for LTBI diagnosis is
available. Thus, since improved tests to diagnose M. tuberculosis infection are
required, we assessed the efficacy of several M. tuberculosis latency antigens.
BCG-vaccinated healthy donors (HD) and tuberculosis (TB) patients were recruited.
QuantiFERON-TB Gold In-Tube, TST and clinical data were used to differentiate
LTBI. IFN-gamma production against CFP-10, ESAT-6, Rv2624c, Rv2626c and Rv2628
antigens was tested in peripheral blood mononuclear cells. LTBI subjects secreted
significantly higher IFN-gamma levels against Rv2626c than HD. Additionally,
Rv2626c peptide pools to which only LTBI responded were identified, and their
cumulative IFN-gamma response improved LTBI discrimination. Interestingly, whole
blood stimulation with Rv2626c allowed the discrimination between active and
latent infections, since TB patients did not secrete IFN-gamma against Rv2626c,
in contrast to CFP-10 + ESAT-6 stimulation that induced IFN-gamma response from
both LTBI and TB patients. ROC analysis confirmed that Rv2626c discriminated LTBI
from HD and TB patients. Therefore, since only LTBI recognizes specific epitopes
from Rv2626c, this antigen could improve LTBI diagnosis, even in BCG-vaccinated
people.
PMID- 26425697
TI - Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep
Brain Stimulation.
AB - Although deep brain stimulation (DBS) shows promising efficacy as a therapy for
intractable depression, the neurobiological bases underlying its therapeutic
action remain largely unknown. The present study was aimed at characterizing the
effects of infralimbic prefrontal cortex (IL-PFC) DBS on several pre-clinical
markers of the antidepressant-like response and at investigating putative non
neuronal mechanism underlying DBS action. We found that DBS induced an
antidepressant-like response that was prevented by IL-PFC neuronal lesion and by
adenosine A1 receptor antagonists including caffeine. Moreover, high frequency
DBS induced a rapid increase of hippocampal mitosis and reversed the effects of
stress on hippocampal synaptic metaplasticity. In addition, DBS increased
spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity
and synaptogenesis. Unambiguously, a local glial lesion counteracted all these
neurobiological effects of DBS. Further in vivo electrophysiological results
revealed that this astrocytic modulation of DBS involved adenosine A1 receptors
and K(+) buffering system. Finally, a glial lesion within the site of stimulation
failed to counteract the beneficial effects of low frequency (30 Hz) DBS. It is
proposed that an unaltered neuronal-glial system constitutes a major prerequisite
to optimize antidepressant DBS efficacy. It is also suggested that decreasing
frequency could heighten antidepressant response of partial responders.
PMID- 26425698
TI - Over-expression of XIST, the Master Gene for X Chromosome Inactivation, in
Females With Major Affective Disorders.
AB - BACKGROUND: Psychiatric disorders are common mental disorders without a
pathological biomarker. Classic genetic studies found that an extra X chromosome
frequently causes psychiatric symptoms in patients with either Klinefelter
syndrome (XXY) or Triple X syndrome (XXX). Over-dosage of some X-linked escapee
genes was suggested to cause psychiatric disorders. However, relevance of these
rare genetic diseases to the pathogenesis of psychiatric disorders in the general
population of psychiatric patients is unknown. METHODS: XIST and several X-linked
genes were studied in 36 lymphoblastoid cell lines from healthy females and 60
lymphoblastoid cell lines from female patients with either bipolar disorder or
recurrent major depression. XIST and KDM5C expression was also quantified in 48
RNA samples from postmortem human brains of healthy female controls and female
psychiatric patients. FINDINGS: We found that the XIST gene, a master in control
of X chromosome inactivation (XCI), is significantly over-expressed (p = 1 * 10(-
7), corrected after multiple comparisons) in the lymphoblastoid cells of female
patients with either bipolar disorder or major depression. The X-linked escapee
gene KDM5C also displays significant up-regulation (p = 5.3 * 10(- 7), corrected
after multiple comparisons) in the patients' cells. Expression of XIST and KDM5C
is highly correlated (Pearson's coefficient, r = 0.78, p = 1.3 * 10(- 13)).
Studies on human postmortem brains supported over-expression of the XIST gene in
female psychiatric patients. INTERPRETATIONS: We propose that over-expression of
XIST may cause or result from subtle alteration of XCI, which up-regulates the
expression of some X-linked escapee genes including KDM5C. Over-expression of X
linked genes could be a common mechanism for the development of psychiatric
disorders between patients with those rare genetic diseases and the general
population of female psychiatric patients with XIST over-expression. Our studies
suggest that XIST and KDM5C expression could be used as a biological marker for
diagnosis of psychiatric disorders in a significantly large subset of female
patients. RESEARCH IN CONTEXT: Due to lack of biological markers, diagnosis and
treatment of psychiatric disorders are subjective. There is utmost urgency to
identify biomarkers for clinics, research, and drug development. We found that
XIST and KDM5C gene expression may be used as a biological marker for diagnosis
of major affective disorders in a significantly large subset of female patients
from the general population. Our studies show that over-expression of XIST and
some X-linked escapee genes may be a common mechanism for development of
psychiatric disorders between the patients with rare genetic diseases (XXY or
XXX) and the general population of female psychiatric patients.
PMID- 26425700
TI - Diagnostic Performance of Plasma DNA Methylation Profiles in Lung Cancer,
Pulmonary Fibrosis and COPD.
AB - Disease-specific alterations of the cell-free DNA methylation status are
frequently found in serum samples and are currently considered to be suitable
biomarkers. Candidate markers were identified by bisulfite conversion-based
genome-wide methylation screening of lung tissue from lung cancer, fibrotic ILD,
and COPD. cfDNA from 400 MUl serum (n = 204) served to test the diagnostic
performance of these markers. Following methylation-sensitive restriction enzyme
digestion and enrichment of methylated DNA via targeted amplification
(multiplexed MSRE enrichment), a total of 96 markers were addressed by highly
parallel qPCR. Lung cancer was efficiently separated from non-cancer and controls
with a sensitivity of 87.8%, (95%CI: 0.67-0.97) and specificity 90.2%, (95%CI:
0.65-0.98). Cancer was distinguished from ILD with a specificity of 88%, (95%CI:
0.57-1), and COPD from cancer with a specificity of 88% (95%CI: 0.64-0.97).
Separation of ILD from COPD and controls was possible with a sensitivity of 63.1%
(95%CI: 0.4-0.78) and a specificity of 70% (95%CI: 0.54-0.81). The results were
confirmed using an independent sample set (n = 46) by use of the four top markers
discovered in the study (HOXD10, PAX9, PTPRN2, and STAG3) yielding an AUC of 0.85
(95%CI: 0.72-0.95). This technique was capable of distinguishing interrelated
complex pulmonary diseases suggesting that multiplexed MSRE enrichment might be
useful for simple and reliable diagnosis of diverse multifactorial disease
states.
PMID- 26425701
TI - A Retrospective Analysis of the Significance of Haemoglobin SS and SC in Disease
Outcome in Patients With Sickle Cell Disease and Dengue Fever.
AB - BACKGROUND: Little is known about the significance of haemoglobin genotype in
dengue fever severity. This study was undertaken to determine the case fatality
ratio and the impact of genotype in patients with sickle cell disease and
confirmed dengue fever. METHODS: This retrospective analysis included 40 patients
with confirmed dengue and sickle cell disease, during the study period (2010
2012). FINDINGS: There was a significantly higher case fatality ratio, 12.5%
among patients with either haemoglobin SC disease or homozygous SS disease when
compared to that of the general population 0.41% (p < 0.0001). The unadjusted
odds of dying among those with haemoglobin SC disease compared with the group
with homozygous SS disease was OR = 4.4 (95% CI 0.6 to 31.7). The predictors of
mortality independent of sickle cell disease genotype were haemoglobin
concentration at presentation OR = 0.57 (95% CI, 0.35 to 0.94) and the change in
haemoglobin concentration from steady state OR = 0.59 (95% CI, 0.37 to 0.94).
Adjusting for haemoglobin concentration at presentation increased the risk of
death for the SC genotype relative to SS genotype OR = 13.4 (95% CI 1.1 to
160.3). INTERPRETATION: The risk of fatal dengue may be higher among patients
with a relatively mild genotype (haemoglobin SC).
PMID- 26425699
TI - A Multi-Dimensional and Integrative Approach to Examining the High-Risk and Ultra
High-Risk Stages of Bipolar Disorder.
AB - BACKGROUND: Validating the high-risk (HR) and ultra-high-risk (UHR) stages of
bipolar disorder (BP) may help enable early intervention strategies. METHODS: We
followed up with 44 offspring of parents with BP, subdividing into the HR and UHR
categories. The offspring were aged 8-28 years and were free of any current DSM
IV diagnoses. Our multilevel, integrative approach encompassed gray matter (GM)
volumes, brain network connectivity, neuropsychological performance, and clinical
outcomes. FINDINGS: Compared with the healthy controls (HCs) (n = 33), the HR
offspring (n = 26) showed GM volume reductions in the right orbitofrontal cortex.
Compared with the HR offspring, the UHR offspring (n = 18) exhibited increased GM
volumes in four regions. Both the HR and UHR offspring displayed abnormalities in
the inferior occipital cortex regarding the measures of degree and centrality,
reflecting the connections and roles of the region, respectively. In the UHR
versus the HR offspring, the UHR offspring exhibited upwards-shifted small world
topologies that reflect high clustering and efficiency in the brain networks.
Compared with the HCs, the UHR offspring had significantly lower assortativity,
which was suggestive of vulnerability. Finally, processing speed, visual-spatial,
and general function were impaired in the UHR offspring but not in the HR
offspring. INTERPRETATION: The abnormalities observed in the HR offspring appear
to be inherited, whereas those associated with the UHR offspring represent stage
specific changes predisposing them to developing the disorder.
PMID- 26425702
TI - Pathogenicity of Anti-ADAMTS13 Autoantibodies in Acquired Thrombotic
Thrombocytopenic Purpura.
AB - BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune
disease in which anti-ADAMTS13 autoantibodies cause severe enzyme deficiency.
ADAMTS13 deficiency causes the loss of regulation of von Willebrand factor
multimeric size and platelet-tethering function, which results in the formation
of disseminated microvascular platelet microthrombi. Precisely how anti-ADAMTS13
autoantibodies, or antibody subsets, cause ADAMTS13 deficiency (ADAMTS13 activity
generally < 10%) has not been formally investigated. METHODS: We analysed 92
acquired TTP episodes at presentation, through treatment and remission/relapse
using epitope mapping and functional analyses to understand the pathogenic
mechanisms of anti-ADAMTS13 IgG. RESULTS: 89/92 of TTP episodes had IgG
recognising the ADAMTS13 N-terminal domains. The central spacer domain was the
only N-terminal antigenic target detected. 38/92 TTP episodes had autoantibodies
recognising the N-terminal domains alone; 54/92 TTP episodes also had antibodies
against the ADAMTS13 C-terminal domains (TSP2-8 and/or CUB domains). Changes in
autoantibody specificity were detected in 9/16 patients at relapse, suggesting a
continued development of the disease. Functional analyses on IgG from 43 patients
revealed inhibitory IgG were limited to anti-spacer domain antibodies. However,
15/43 patients had autoantibodies with no detectable inhibitory action and as
many as 32/43 patients had autoantibodies with inhibitory function that was
insufficient to account for the severe deficiency state, suggesting that in many
patients there is an alternative pathogenic mechanism. We therefore analysed
plasma ADAMTS13 antigen levels in 91 acquired TTP presentation samples. We
demonstrated markedly reduced ADAMTS13 antigen levels in all presentation
samples, median 6% normal (range 0-47%), with 84/91 patients having < 25%
ADAMTS13 antigen. ADAMTS13 antigen in the lowest quartile at first presentation
was associated with increased mortality (odds ratio 5.7). CONCLUSIONS: Anti
spacer domain autoantibodies are the major inhibitory antibodies in acquired TTP.
However, depletion of ADAMTS13 antigen (rather than enzyme inhibition) is a
dominant pathogenic mechanism. ADAMTS13 antigen levels at presentation have
prognostic significance. Taken together, our results provide new insights into
the pathophysiology of acquired TTP.
PMID- 26425703
TI - Trastuzumab Induces an Immediate, Transient Volume Increase in Humans: A
Randomised Placebo-Controlled Trial.
AB - BACKGROUND: The exact extent of and the mechanism by which trastuzumab causes
cardiac side effects are not completely unravelled. We investigated the
(cardiotoxic) side effects of trastuzumab in a relatively large homogeneous
population. METHODS: Healthy male volunteers (n = 54) with a left ventricle
ejection fraction (LVEF) > 55% were administered 6 mg/kg trastuzumab (n = 46) IV
in 90 min in a placebo-controlled, parallel study. Placebo consisted of 0 . 9%
NaCl (n = 8). Assessments included body weight, routine and cardiac laboratory
markers and serial echocardiographic examinations (8 placebo and 9 trastuzumab
treated participants) up to 63 days after dosing. Statistical analysis was done
using repeated measurements of variance. FINDINGS: Following trastuzumab
infusion, fluid retention was observed: mean body weight increased over the first
4 days post-administration with 0 . 4 kg (95%-confidence interval: - 0 . 2, 0 .
9, p = 0 . 2261) compared to placebo, mean haemoglobin concentration decreased
with 0 . 3 mM (- 0 . 6, - 0 . 1; p = 0 . 0043), as did haematocrit (- 0 . 013 L/L
[- 0 . 024, - 0 . 002], p = 0 . 0216), and protein (- 2 g/L [- 4, - 0], p = 0 .
0443) and albumin (- 2 g/L [- 3, - 1], p < 0 . 0001) concentrations. Elevations
in NT-proBNP levels, parallel to the weight increase, were observed in individual
cases, but not on a group level. Troponin-T concentrations did not increase. The
only echocardiographic parameter that changed significantly at all studied dose
levels was E/A-ratio, a load-dependent parameter: from 1 . 81 (SD 0 . 42) to 1 .
98 (0 . 31) 3-5 days after administration, contrast to placebo of 0 . 57 (90%-CI:
0 . 21-0 . 93, p = 0 . 0034). Ejection fraction and pulsed-wave Doppler recorded
parameters remained unchanged. INTERPRETATION: Single dose administration of
trastuzumab in humans is associated with an immediate, transient extracellular
volume increase, either as a primary or secondary (compensatory) response, which
can be detected easily using routine clinical assessments. Echocardiographic
changes, both short and long term, could not be found after single dose
administration to drug-naive patients.
PMID- 26425704
TI - Telomere G-tail Length is a Promising Biomarker Related to White Matter Lesions
and Endothelial Dysfunction in Patients With Cardiovascular Risk: A Cross
sectional Study.
AB - BACKGROUND: The telomeric 3'-overhang (G-tail) length is essential for the
biological effects of telomere dysfunction in vitro, but the association of
length with aging and cardiovascular risk is unclear in humans. We investigated
the association between the telomere G-tail length of leukocytes and
cardiovascular risk, age-related white matter changes (ARWMCs), and endothelial
function. METHODS: Patients with a history of cerebrovascular disease and
comorbidity were enrolled (n = 102; 69 males and 33 females, 70.1 +/- 9.2 years).
Total telomere and telomere G-tail lengths were measured using a hybridization
protection assay. Endothelial function was evaluated by ultrasound assessment of
brachial flow-mediated dilation (FMD). FINDINGS: Shortened telomere G-tail length
was associated with age and Framingham risk score (P = 0.018 and P = 0.012). In
addition, telomere G-tail length was positively correlated with FMD values (P =
0.031) and negatively with the severity of ARWMCs (P = 0.002). On multivariate
regression analysis, telomere G-tail length was independently associated with FMD
values (P = 0.022) and the severity of ARWMCs (P = 0.033), whereas total telomere
length was not associated with these indicators. INTERPRETATION: Telomere G-tail
length is associated with age and vascular risk factors, and might be superior to
total telomere length as a marker of endothelial dysfunction and ARWMC severity.
PMID- 26425708
TI - Brain metastasis in two patients with stage IA papillary serous carcinoma of the
uterus.
AB - We report two cases of brain metastasis in patients initially diagnosed with
extremely early stage UPSC after extensive staging surgery. They did not receive
either adjuvant chemotherapy or adjuvant pelvic or vaginal cuff radiation. At the
same time that these patients were diagnosed with systemic metastasis, they both
had a local "drop" metastasis in the vulva or the vaginal cuff. After the initial
response to palliative chemotherapy, they both developed brain metastasis. The
pattern of recurrence with the lack of adjuvant treatment underscores the urgent
need in further evaluation of the potential benefits of adjuvant treatment,
including chemotherapy and possibly in combination with radiation in this highly
aggressive disease.
PMID- 26425705
TI - Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic
and Simple Obesity in Children.
AB - Gut microbiota has been implicated as a pivotal contributing factor in diet
related obesity; however, its role in development of disease phenotypes in human
genetic obesity such as Prader-Willi syndrome (PWS) remains elusive. In this
hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21)
children, a diet rich in non-digestible carbohydrates induced significant weight
loss and concomitant structural changes of the gut microbiota together with
reduction of serum antigen load and alleviation of inflammation. Co-abundance
network analysis of 161 prevalent bacterial draft genomes assembled directly from
metagenomic datasets showed relative increase of functional genome groups for
acetate production from carbohydrates fermentation. NMR-based metabolomic
profiling of urine showed diet-induced overall changes of host metabotypes and
identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host
bacteria co-metabolites known to induce metabolic deteriorations. Specific
bacterial genomes that were correlated with urine levels of these detrimental co
metabolites were found to encode enzyme genes for production of their precursors
by fermentation of choline or tryptophan in the gut. When transplanted into germ
free mice, the pre-intervention gut microbiota induced higher inflammation and
larger adipocytes compared with the post-intervention microbiota from the same
volunteer. Our multi-omics-based systems analysis indicates a significant
etiological contribution of dysbiotic gut microbiota to both genetic and simple
obesity in children, implicating a potentially effective target for alleviation.
RESEARCH IN CONTEXT: Poorly managed diet and genetic mutations are the two
primary driving forces behind the devastating epidemic of obesity-related
diseases. Lack of understanding of the molecular chain of causation between the
driving forces and the disease endpoints retards progress in prevention and
treatment of the diseases. We found that children genetically obese with Prader
Willi syndrome shared a similar dysbiosis in their gut microbiota with those
having diet-related obesity. A diet rich in non-digestible but fermentable
carbohydrates significantly promoted beneficial groups of bacteria and reduced
toxin-producers, which contributes to the alleviation of metabolic deteriorations
in obesity regardless of the primary driving forces.
PMID- 26425709
TI - Fertility-sparing management of a stage IB1 small cell neuroendocrine cervical
carcinoma with radical abdominal trachelectomy and adjuvant chemotherapy.
AB - *Neuroendocrine (NEC) tumors of the cervix are very rare and aggressive.*We
present a case of Stage IB1 disease managed with fertility-sparing
surgery.*Further investigation into fertility-sparing surgery is warranted.
PMID- 26425710
TI - Endometrioid adenocarcinoma associated with endometrial stromal sarcoma: A rare,
often unrecognized collision tumor.
AB - We are reporting 3 cases of the uterine corpus with collision of endometrioid
adenocarcinoma (EAC) with endometrial stromal sarcoma (ESS). The patients' ages
ranged from 36 to 59 years old. The major clinical presentation was abnormal
uterine bleeding. Microscopically, all 3 cases presented with 2 separate
components, EAC Grade 1 and ESS (one low grade and two high grades). The EAC
component ranged from 10% to 70%, and the ESS component ranged from 30% to 70% of
total tumor volume. The EAC component was stage 1A in two cases and stage II in
one case. The ESS component was stages IA, IIB, and IIIB. Adjuvant hormonal
therapy was administrated to one patient while a second patient was treated with
chemo/radiation therapy. Two patients were still alive with no evidence of
disease at 4 years post-therapy. One patient was lost for follow-up. Collision
tumor should be distinguished from carcinosarcoma due to its different treatment
modality, outcome and, prognosis.
PMID- 26425706
TI - Interventions to Improve Neonatal Health and Later Survival: An Overview of
Systematic Reviews.
AB - BACKGROUND: Evidence-based interventions and strategies are needed to improve
child survival in countries with a high burden of neonatal and child mortality.
An overview of systematic reviews can focus implementation on the most effective
ways to increase child survival. METHODS: In this overview we included published
Cochrane and other systematic reviews of experimental and observational studies
on antenatal, childbirth, postnatal and child health interventions aiming to
prevent perinatal/neonatal and child mortality using the WHO list of essential
interventions. We assessed the methodological quality of the reviews using the
AMSTAR criteria and assessed the quality of the outcomes using the GRADE
approach. Based on the findings from GRADE criteria, interventions were
summarized as effective, promising or ineffective. FINDINGS: The overview
identified 148 Cochrane and other systematic reviews on 61 reproductive,
maternal, newborn and child health interventions. Of these, only 57 reviews
reported mortality outcomes. Using the GRADE approach, antenatal corticosteroids
for preventing neonatal respiratory distress syndrome in preterm infants; early
initiation of breastfeeding; hygienic cord care; kangaroo care for preterm
infants; provision and promotion of use of insecticide treated bed nets (ITNs)
for children; and vitamin A supplementation for infants from six months of age,
were identified as clearly effective interventions for reducing neonatal, infant
or child mortality. Antenatal care, tetanus immunization in pregnancy,
prophylactic antimalarials during pregnancy, induction of labour for prolonged
pregnancy, case management of neonatal sepsis, meningitis and pneumonia,
prophylactic and therapeutic use of surfactant, continuous positive airway
pressure for neonatal resuscitation, case management of childhood malaria and
pneumonia, vitamin A as part of treatment for measles associated pneumonia for
children above 6 months, and home visits across the continuum of care, were
identified as promising interventions for reducing neonatal, infant, child or
perinatal mortality. INTERPRETATION: Comprehensive adoption of the above six
effective and 11 promising interventions can improve neonatal and child survival
around the world. Choice of intervention and degree of implementation currently
depends on resources available and policies in individual countries and
geographical settings. FUNDING: This review was part of doctoral thesis which was
funded by University of Adelaide, Australia.
PMID- 26425711
TI - Menopausal hormone therapy and mortality among women diagnosed with ovarian
cancer in the NIH-AARP Diet and Health Study.
AB - BACKGROUND: Although menopausal hormone therapy (MHT) use has been linked with an
increased risk of ovarian cancer, whether pre-diagnosis MHT use affects ovarian
cancer-specific mortality is unknown. METHODS: Our analysis included 395 incident
epithelial ovarian cancer patients with data on pre-diagnosis MHT use from the
National Institutes of Health-AARP (NIH-AARP) Diet and Health Study. We used Cox
proportional hazards regression models to estimate hazard ratios (HRs) and 95%
confidence intervals (CIs) for MHT type and ovarian cancer-specific mortality,
adjusted for tumor characteristics, treatment, and other risk factors. Effect
modification by histology (serous vs. non-serous) was examined using likelihood
ratio tests comparing models with and without interaction terms between MHT type
and histology. RESULTS: Ovarian cancer-specific mortality was not associated with
pre-diagnosis estrogen-only therapy (ET) (HR = 1.09, 95% CI = 0.70-1.68) or
estrogen plus progestin-only therapy (EPT) (HR = 0.97, 95% CI = 0.68-1.38).
Neither recency of use nor specific regimen of EPT-only (sequential vs.
continuous) was related to mortality. In analyses stratified by histology, no
significant association between MHT type and ovarian cancer-specific mortality
was observed among serous or non-serous cases; however, a significant interaction
between MHT type and histology was noted (p-heterogeneity = 0.01). CONCLUSION:
Our results suggest that pre-diagnosis MHT use is not related to risk of ovarian
cancer-specific death.
PMID- 26425712
TI - Spontaneous ureteral rupture during concurrent chemoradiotherapy in a woman with
uterine cervical cancer.
AB - Spontaneous rupture of the renal pelvis and ureter is associated with obstruction
of the urinary collecting system, but is rarely caused by tumors. We describe our
experience with a patient who had uterine cervical cancer with mild hydroureter
in whom spontaneous ureteral rupture occurred during concurrent
chemoradiotherapy. The patient was a 66-year-old woman with stage IIIB uterine
cervical cancer and mild hydroureter who received concurrent chemoradiotherapy.
The patient felt uncontrolled right-side abdominal pain caused by ureteral
rupture after she was given hydration and an intravenous bolus injection of
furosemide during the first week of chemoradiotherapy. Contrast-enhanced computed
tomography was more useful than ultrasonography for diagnosis of the ureteral
rupture. The ureteral rupture in our patient was attributed to a rapid rise in
the pressure of the urinary collecting system caused by hydration and the bolus
injection of furosemide. Placement of a double-J stent before starting concurrent
chemoradiotherapy may help to prevent ureteral rupture in patients who have
uterine cervical cancer with mild hydroureter.
PMID- 26425713
TI - Solitary ovarian plasmacytoma. A case report and review of literature.
AB - *A patient with rare solitary ovarian plasmacytoma is reported*Diagnostic work-up
is mandatory to rule out ovarian involvement as part of multiple myeloma.*After
complete surgical resection, the prognosis appears to be very favorable.
PMID- 26425714
TI - The problem of late ovarian metastases from primary cervical adenocarcinoma.
AB - *Ovarian metastases can occur after hysterectomy for cervical
adenocarcinoma.*Cervical adenocarcinoma and ovarian metastases showed common
genetic profiles.*Most likely mechanism is trans-tubal spread of neoplastic cells
via ovarian stroma.
PMID- 26425715
TI - WWP2 and its association with PTEN in endometrial cancer.
AB - We wished to determine if WWP2 gene expression and PTEN protein levels inversely
correlate in human endometrial cancer tissues. Fifty-one endometrioid endometrial
tumors and five normal endometrial controls were available for analysis. PTEN
protein levels were assessed by immunohistochemistry (IHC). WWP2 and PTEN gene
expression were quantitated by RT PCR. Clinical and pathologic information was
collected by chart review. We found that in tumors with low PTEN protein but
normal mRNA expression there were significantly higher levels of WWP2 expression
(p = 0.0017). Increased WWP2 expression was not associated with clinical
prognostic factors including lymphovascular space invasion, >= 50% myometrial
invasion, grade, stage or recurrence. WWP2 expression was not different
statistically between tumors and normal controls (p = NS). Therefore, in this
cohort, tumors with low PTEN protein but normal mRNA expression had elevated
levels of WWP2 expression. This suggests that WWP2 may be playing a role in PTEN
degradation in endometrial cancer.
PMID- 26425716
TI - Primary endometrial uterine Burkitt lymphoma in a 65-year-old woman.
AB - *Primary Burkitt lymphoma of the uterus is a rare disease.*Differential of
postmenopausal bleeding and night sweats should include lymphoma.*Outpatient
endometrial sampling expedites diagnosis of endometrial malignancy.
PMID- 26425717
TI - Breast cancer metastasis to the vulva 20 years remote from initial diagnosis: A
case report and literature review.
AB - *This is the 20th documented case of metastatic breast carcinoma to the
vulva.*Greater than 21 years have passed from initial diagnosis to vulvar
metastasis.*Existing literature supports long term surveillance in women with
invasive lobular carcinoma of the breast.
PMID- 26425719
TI - Palladium interstitial implant in combination with external beam radiotherapy and
chemotherapy for the definitive treatment of a female urethral carcinoma.
AB - Primary urethral cancer is a rare diagnosis, especially in females. This report
presents the utilization of a palladium interstitial implant and a review of the
retrospective data published on the management of female urethral cancer.
Excellent local control and survival has been obtained with the use of a
palladium interstitial implant in combination with external beam radiotherapy and
concurrent chemotherapy. This modality represents a novel and effective way to
treat primary urethral cancer in females.
PMID- 26425718
TI - Characteristics of ovarian tumors of low malignant potential in BRCA mutation
carriers: A case series.
AB - *Tumor characteristics of 5 cases of ovarian tumor of low malignant potential
(LMP) with BRCA mutation were examined.*Young age, BRCA1 mutation, and presence
of invasive implants may be characteristics of BRCA carriers with ovarian LMP.
PMID- 26425720
TI - Ureteroarterial fistula following retrograde ureteral stenting in a patient with
a double-barreled wet colostomy for cervical cancer.
AB - *Ureteroarterial fistula (UAF) is a rare cause of massive hematuria.*Percutaneous
retrograde ureteral stents via DBWC can be done safely in the compliant patient
for improved comfort.*Understanding the anatomy, risks, and minimally invasive
treatment options for UAF is important for prompt patient care.
PMID- 26425721
TI - The cost implications of the use of pegylated liposomal doxorubicin when choosing
an anthracycline for the treatment of platinum-resistant ovarian cancer: A low
value intervention?
PMID- 26425722
TI - Lumbee Native American ancestry and the incidence of aggressive histologic
subtypes of endometrial cancer.
AB - OBJECTIVE: The Lumbee Indian tribe is the largest Native American tribe in North
Carolina, with about 55,000 enrolled members who mostly reside in southeastern
counties. We evaluated whether Lumbee heritage is associated with high-risk
histologic subtypes of endometrial cancer. METHODS: We retrospectively analyzed
the available records from IRB-approved endometrial cancer databases at two
institutions of patients of Lumbee descent (year of diagnosis range 1980-2014).
Each Lumbee case was matched by age, year of diagnosis, and BMI to two non-Lumbee
controls. Chi-square test was used to compare categorical associations. Kaplan
Meier methods and log-rank test were used to display and compare disease-free
survival (DFS) and overall survival (OS). Multivariate Cox proportional hazards
regression was used to adjust for age and BMI while testing cohort as a predictor
of DFS and OS. RESULTS: Among 108 subjects, 10/35 (29%) Lumbee and 19/72 (26%)
non-Lumbee subjects had high-risk (serous/clear cell/carcinosarcoma) histologic
types (p = 0.8). 12/35 (34%) Lumbee and 24/72 (33%) non-Lumbee subjects had grade
3 tumors (p = 0.9). 5/33 (15%) Lumbee and 13/72 (18%) non-Lumbee had advanced
stage endometrial cancer at diagnosis (p = 0.7). Lumbee ancestry was not
associated with worse survival outcomes. OS (p = 0.054) and DFS (p = 0.01) were
both worse in Blacks compared to Lumbee and White subjects. CONCLUSION: In this
retrospective cohort analysis, Lumbee Native American ancestry was not a
significant independent predictor of rates of high-risk histological subtypes of
endometrial cancer or poor survival outcomes.
PMID- 26425723
TI - FGFR3-TACC3: A novel gene fusion in cervical cancer.
AB - Cervical cancer epitomizes the success of cancer prevention through the human
papillomavirus (HPV) vaccine, but significant challenges remain in the treatment
of advanced disease. We report the first three cases of cervical carcinoma
harboring an FGFR3-TACC3 fusion, which serves as a novel therapeutic target. The
fusion, identified by comprehensive genomic profiling, activates the FGFR pathway
that has been implicated in HPV-driven carcinogenesis. One of the patients whose
tumor contained the FGFR3-TACC3 fusion was treated with an investigational FGFR
tyrosine kinase inhibitor. Concomitant molecular alterations involving the
PI3K/AKT/mTOR and RAF/MEK pathways were also identified and suggest other
treatment strategies that deserve investigation. This case series highlights the
role of comprehensive genomic profiling in the identification of new therapeutic
targets and in targeted therapy selection for patients with cervical cancer.
PMID- 26425724
TI - Novel treatment of a central type, primitive neuroectodermal tumor of the ovary
with postoperative pediatric medulloblastoma chemotherapy regimen: A case report
and review of the literature.
AB - *Central type primitive neuroectodermal tumor (cPNET) of the ovary is difficult
to treat.*Etoposide, cisplatin and cyclophosphamide is a pediatric
medulloblastoma regimen.*Our case with cPNET responded to this combination
chemotherapy.
PMID- 26425725
TI - Debulking surgery and hyperthermic intraperitoneal chemotherapy in the management
of a recurrent aggressive uterine myxoid leiomyosarcoma with peritoneal
dissemination.
AB - *A rare case of recurrent peritoneal sarcomatosis (PS) arising from aggressive
uterine myxoid leiomyosarcoma was described.*Cytoreductive surgery with
hyperthermic intraperitoneal chemotherapy (HIPEC) has the potential to improve
outcomes in PS from uterine sarcoma.*Careful patient selection for cytoreductive
surgery with HIPEC is important to achieve better outcomes in PS.
PMID- 26425726
TI - Hepatoid carcinoma of the ovary: A case report and review of the literature.
AB - Primary hepatoid carcinoma of the ovary (HCO) is a rare aggressive tumor that
typically presents at an advanced stage in postmenopausal women with unilateral
or bilateral ovarian masses and elevated AFP and CA125. We report a case of HCO
in a 73 year-old woman who presented with abdominal distention, weight loss, and
a large lower abdominal mass. Postoperative serum AFP was markedly elevated and
trended down with initiation of chemotherapy. Review of the literature revealed
thirty-two reported cases with no consensus on histogenesis or consistent
immunohistochemical profile other than positive AFP staining in all but one case.
Although the optimal treatment has not yet been determined, tumor debulking
surgery followed by a platinum and taxane based chemotherapy regimen has shown
promise. Both serum AFP and CA125 appear to have prognostic value and can be used
to follow response to treatment and screen for recurrence.
PMID- 26425727
TI - Endometrioid adenocarcinoma arising from deep infiltrating endometriosis
involving the bladder: A case report and review of the literature.
AB - *Malignant transformation of deep infiltrating endometriosis involving the
bladder is quite rare.*We review eight relevant cases which have been
reported.*This is the second case fulfilling Sampson and Scott criteria.
PMID- 26425728
TI - Almost half of women with endometrial cancer or hyperplasia do not know that
obesity affects their cancer risk.
PMID- 26425729
TI - Fatal cardiac tamponade following cytoreductive surgery for serous carcinoma of
the ovary.
AB - *Pericardial effusion may be present early in the disease process in patients
with ovarian cancer.*Even a small pericardial effusion may become clinically
apparent in the setting of concomitant pleural effusion(s).*Cardiac tamponade
should be considered in the differential diagnosis of postoperative hemodynamic
instability to facilitate timely intervention.
PMID- 26425730
TI - In-vitro maturation and cryopreservation of oocytes at the time of oophorectomy.
AB - A 27 year old female presented for fertility preservation prior to undergoing
pelvic radiotherapy. She had previously undergone a radical laparoscopic
hysterectomy for cervical carcinoma seven months earlier. A trans-vaginal oocyte
aspiration was not advisable due to a vaginal recurrence of the disease. Due to a
polycystic ovarian morphology (PCO), follicle stimulating hormone (FSH) priming
with no human chorionic gonadotrophin (hCG) trigger was performed prior to
oophorectomy followed by ex-vivo oocyte aspiration and in vitro maturation (IVM).
All visualized follicles were punctured and follicular fluid aspirated. There
were 22 immature oocytes identified and placed into maturation culture for 24 h.
After this time, 15 oocytes were deemed to be mature and suitable for
vitrification. Following an additional 24 h in maturation culture of the
remaining 7 oocytes, three more were suitable for cryopreservation. The patient
recovered well and progressed to radiotherapy three days later. This report
demonstrates the use of IVM treatment to store oocytes for oncology patients in
time-limited circumstances.
PMID- 26425731
TI - The Use of Tutomesh for a Tension-Free and Tridimensional Repair of Uterovaginal
and Vaginal Vault Prolapse: Preliminary Report.
AB - Objective. To evaluate efficacy in terms of vaginal capacity, coital function,
and recurrence prevention of a new biological mesh of bovine pericardium
(Tutomesh) in the repair of severe POP. Methods. Thirty cases of patients
suffering from stage III uterine or apical prolapse undergone surgical repair by
means of a modified sacrospinous ligament suspension combined with mesh
attachment to both the cardinal ligaments, posterior and anterior colporrhaphy,
and perineal body fixation. The mesh was replaced inside the pelvis with the goal
of reconstructing the tridimensional fascial disposition of the structures
sustaining the correct axis of vagina. Follow-up was done at 12 months with POPIQ
analysis. Results. One total mesh failure occurred early after surgery due to
marked deficiency of anatomy. Two cystoceles were observed at 12 months in two
patients treated for apical prolapse where anterior repair was not performed. Two
other patients developed a de novo SUI at 12 months. No reported abnormalities of
coital function or dyspareunia were ever found after surgery. Conclusions. It is
possible that the utilization of a tension-free and tridimensional placement of
Tutomesh might favor a more physiologic reconstruction of the vaginal axis as
compared with traditional sacrospinous ligament suspension.
PMID- 26425732
TI - Teamwork Assessment Tools in Modern Surgical Practice: A Systematic Review.
AB - Introduction. Deficiencies in teamwork skills have been shown to contribute to
the occurrence of adverse events during surgery. Consequently, several teamwork
assessment tools have been developed to evaluate trainee nontechnical
performance. This paper aims to provide an overview of these instruments and
review the validity of each tool. Furthermore, the present paper aims to review
the deficiencies surrounding training and propose several recommendations to
address these issues. Methods. A systematic literature search was conducted to
identify teamwork assessment tools using MEDLINE (1946 to August 2015), EMBASE
(1974 to August 2015), and PsycINFO (1806 to August 2015) databases. Results.
Eight assessment tools which encompass aspects of teamwork were identified. The
Nontechnical Skills for Surgeons (NOTSS) assessment was found to possess the
highest level of validity from a variety of sources; reliability and
acceptability have also been established for this tool. Conclusions. Deficits in
current surgical training pathways have prompted several recommendations to meet
the evolving requirements of surgeons. Recommendations from the current paper
include integration of teamwork training and assessment into medical school
curricula, standardised formal training of assessors to ensure accurate
evaluation of nontechnical skill acquisition, and integration of concurrent
technical and nontechnical skills training throughout training.
PMID- 26425733
TI - Current Status of Single-Site Robotic Cholecystectomy, its feasibility, economic
and overall impact.
AB - This paper reviews recent, though limited, articles on the topic of robotic
single-site cholecystectomy (RSSC), a relatively new approach that is rapidly
advancing in both research and clinical application. Laparoscopy has typically
been the standard method of performing a cholecystectomy, but recent medical
advances have led to usage of the da Vinci(r) Surgical System robot technology to
assist in performing the procedure. Several studies have compared outcomes of the
RSSC to single-port laparoscopic cholecystectomies and to the traditional
multiport laparoscopic cholecystectomies. Single port advocates think it as a
tool with better cosmetic results and questionable less post-operative pain;
however, single port also limits the maneuverability of the instrument arms,
making some tasks more difficult, bigger single incision, more chances of post
operative hernia. Overall, the RSSC is considered as safe with no worse outcomes
regarding pain, hospital stay length, operative time, and patient satisfaction
when compared to other cholecystectomy methods. Future direction includes
expanding use of the miniature instruments and further advanced tools to overcome
manipulation and visualization limitations. Thus far, though, there may be enough
evidence with these smaller studies to support lack of harm with more use of
resources.
PMID- 26425735
TI - Development of a polymer based fiberoptic magnetostrictive metal detector system.
AB - This paper presents a new metal detector using a fiberoptic magnetostriction
sensor. The metal sensor uses a fiber-optic Mach-Zehnder interferometer with a
newly developed ferromagnetic polymer as the magnetostrictive sensing material.
This polymeric magnetostrictive fiberoptic metal sensor is simple to fabricate,
small in size, and resistant to RF interference (which is common in typical
electromagnetic type metal detectors). Metal detection is based on disruption of
the magnetic flux density across the magnetostriction sensor. In this paper,
characteristics of the material being sensed and magnetic properties of the
ferromagnetic polymers will be discussed.
PMID- 26425736
TI - Synthesis and luminescence modulation of pyrazine-based gold(III) pincer
complexes.
AB - The first examples of pyrazine-based gold(III) pincer complexes are reported;
their intense photoemissions can be modified by protonation, N-alkylation or
metal ions, without the need for altering the ligand framework. Emissions shift
from red (77 K) to blue (298 K) due to thermally activated delayed fluorescence
(TADF).
PMID- 26425737
TI - [Lassa fever and ribavirin].
PMID- 26425734
TI - Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and
infection.
AB - Ascending infection of microbes from the lower genital tract into the amniotic
cavity increases the risk of preterm birth, stillbirth, and newborn infections.
Host defenses that are critical for preventing ascending microbial infection are
not completely understood. Group B Streptococcus (GBS) are Gram-positive bacteria
that frequently colonize the lower genital tract of healthy women but cause
severe infections during pregnancy, leading to preterm birth, stillbirth, or
early-onset newborn infections. We recently described that the GBS pigment is
hemolytic, and increased pigment expression promotes GBS penetration of human
placenta. Here, we show that the GBS hemolytic pigment/lipid toxin and
hyperpigmented GBS strains induce mast cell degranulation, leading to the release
of preformed and proinflammatory mediators. Mast cell-deficient mice exhibit
enhanced bacterial burden, decreased neutrophil mobilization, and decreased
immune responses during systemic GBS infection. In a vaginal colonization model,
hyperpigmented GBS strains showed increased persistence in mast cell-deficient
mice compared to mast cell-proficient mice. Consistent with these observations,
fewer rectovaginal GBS isolates from women in their third trimester of pregnancy
were hyperpigmented/hyperhemolytic. Our work represents the first example of a
bacterial hemolytic lipid that induces mast cell degranulation and emphasizes the
role of mast cells in limiting genital colonization by hyperpigmented GBS.
PMID- 26425738
TI - Hormone crosstalk in plants.
PMID- 26425739
TI - Preface.
PMID- 26425740
TI - Homer Hupf (1933-2015): In memoriam.
PMID- 26425741
TI - Central Retinal Artery Occlusion in a 21-Year-Old Boxer.
PMID- 26425742
TI - Palisaded Encapsulated Neuroma of the Eyelid.
PMID- 26425743
TI - Orbital Choristoma.
PMID- 26425744
TI - Uveal Melanoma Presenting as a Pigmented Conjunctival Lesion.
PMID- 26425745
TI - Retraction notice to 'Design and synthesis of CHAP31, trapoxin B and HC-toxin
based bicyclic tetrapeptides disulfide as potent histone deacetylase inhibitors'
[Bioorg Med Chem 22 (2014) 3850-3855].
PMID- 26425746
TI - 2nd International Conference on Biomedicine and Pharmaceutics (ICBP) 2014.
PMID- 26425747
TI - From The Archives.
PMID- 26425781
TI - Are general surgeons able to accurately self-assess their level of technical
skills?
AB - INTRODUCTION: Self-assessment is a way of improving technical capabilities
without the need for trainer feedback. It can identify areas for improvement and
promote professional medical development. The aim of this review was to identify
whether self-assessment is an accurate form of technical skills appraisal in
general surgery. METHODS: The PubMed, MEDLINE((r)), Embase(TM) and Cochrane
databases were searched for studies assessing the reliability of self-assessment
of technical skills in general surgery. For each study, we recorded the skills
assessed and the evaluation methods used. Common endpoints between studies were
compared to provide recommendations based on the levels of evidence. RESULTS:
Twelve studies met the inclusion criteria from 22,292 initial papers. There was
no level 1 evidence published. All papers compared the correlation between self
appraisal versus an expert score but differed in the technical skills assessment
and the evaluation tools used. The accuracy of self-assessment improved with
increasing experience (level 2 recommendation), age (level 3 recommendation) and
the use of video playback (level 3 recommendation). Accuracy was reduced by
stressful learning environments (level 2 recommendation), lack of familiarity
with assessment tools (level 3 recommendation) and in advanced surgical
procedures (level 3 recommendation). CONCLUSIONS: Evidence exists to support the
reliability of self-assessment of technical skills in general surgery. Several
variables have been shown to affect the accuracy of self-assessment of technical
skills. Future work should focus on evaluating the reliability of self-assessment
during live operating procedures.
PMID- 26425782
TI - A framework for the frontline: How hospitalists can improve healthcare value.
AB - As healthcare costs continue to grow, hospitalists may be able to help patients
and health system administrators make decisions that generate higher-value care.
In this article, we discuss 3 ways hospitalists can contribute to the mission of
delivering value-based healthcare: design innovative strategies to coordinate
care, advocate for appropriate utilization of tests and treatments, and lead
local value-improvement initiatives. We also describe specific tools hospitalists
can use in their daily practice, including the Choosing Wisely lists and the COST
(Culture, Oversight, Systems Change, Training) framework for value-improvement
initiatives.
PMID- 26425783
TI - Can attachment and peer relation constructs predict anxiety in ethnic minority
youths? A longitudinal exploratory study.
AB - Anxiety is the most prevalent psychiatric disturbance in childhood effecting
typically 15-20% of all youth. It has been associated with attachment insecurity
and reduced competence in peer relations. Prior work has been limited by
including mainly White samples, relying on questionnaires, and applying a cross
sectional design. The present study addressed these limitations by considering
how at-risk non-White youth (n = 34) responded to the Friends and Family
Interview (FFI) in middle childhood and how this linked up with anxiety symptoms
and an anxiety diagnosis three years later in early adolescence. Five dimensions
of secure attachment, namely, (i) to mother, (ii) to father, (iii) coherence,
(iv) developmental understanding, and (v) social competence and quality of
contact with best friend in middle childhood, were found to correlate
significantly (and negatively) with self-reported anxiety symptoms. Linear
regression results showed independent influences of female gender, and (low)
quality of best friend contact as the most efficient model predicting anxiety
symptoms. Logistic regression results suggested a model that included female
gender, low social competence, and immature developmental understanding as
efficient predictors of an anxiety diagnosis, evident in only 18% of the sample.
These results point to the usefulness of after-school programs for at-risk
minority youth in promoting peer competence, developmental awareness, and
minimizing anxiety difficulties.
PMID- 26425784
TI - Protostane Triterpenoids from the Rhizome of Alisma orientale Exhibit Inhibitory
Effects on Human Carboxylesterase 2.
AB - Twelve new and 10 known protostane triterpenoids were isolated from the rhizome
of Alisma orientale. Their structures were elucidated based on physical data
analyses, including UV, HRESIMS, NMR experiments ((1)H, (13)C NMR, (1)H-(1)H
COSY, HSQC, HMBC, and NOESY), and induced electronic circular dichroism. New
compounds 1-12 were classified as protostanes (1-10), 29-norprotostane (11), and
24-norprotostane (12) by structure analyses. Furthermore, the inhibitory effects
on human carboxylesterases (hCE-1, hCE-2) of compounds 1-22 were evaluated.
Compounds 2, 6, 9, and 11 showed moderate inhibitory activities and were
selective toward hCE-2 enzymes, with IC50 values of 8.68, 4.72, 4.58, and 2.02
MUM, respectively. The inhibition kinetics of compound 11 toward hCE-2 were
established, and the Ki value was determined as 1.76 MUM using a mixed inhibition
model. The interaction of bioactive compound 11 with hCE-2 was shown using
molecular docking.
PMID- 26425786
TI - Fluorographane: a promising material for bipolar doping of MoS2.
AB - Using first principles calculations we investigate the structural and electronic
properties of interfaces between fluorographane and MoS2. Unsymmetrical
functionalization of graphene with H and F results in an intrinsic dipole moment
perpendicular to the plane of the buckled graphene skeleton. Depending on the
orientation of this dipole moment, the electronic properties of a physically
absorbed MoS2 monolayer can be switched from n- to p-type or vice versa. We show
that one can realize vanishing n-type/p-type Schottky barrier heights when
contacting MoS2 to fluorographane. By applying a perpendicular electric field,
the size of the Schottky barrier and the degree of doping can be tuned. Our
calculations indicate that a fluorographane monolayer is a promising candidate
for bipolar doping of MoS2, which is vital in the design of novel technological
applications based on two-dimensional materials.
PMID- 26425787
TI - Direct costs of acute respiratory infections in a pediatric long-term care
facility.
AB - Acute respiratory tract infections (ARI) are a major burden in pediatric long
term care. We analyzed the financial impact of ARI in 2012-2013. Costs associated
with ARI during the respiratory viral season were ten times greater than during
the non-respiratory viral season, $31 224 and $3242 per 1000 patient-days,
respectively (P < 0.001). ARI are burdensome for pediatric long-term care
facilities not only because of the associated morbidity and mortality, but also
due to the great financial costs of prevention.
PMID- 26425788
TI - Heteromerous Bistricyclic Aromatic Enes: Dynamic Stereochemistry of Xanthylidene
Anthrones.
AB - The heteromerous bistricyclic aromatic ene (BAE) 2,2'-dimethyl-10-(9H
xanthylidene)-9(10H)-anthrone (DMXA) was synthesized by a condensation of 10,10
dichloro-2-methylxanthene with 2-methylanthrone. X-ray crystallography of (E)
DMXA and xanthylidene-anthrone (XA) indicated that the molecules adopt anti
folded conformations with folding dihedral angles of 44 degrees /44 degrees and
39 degrees /41 degrees , respectively. The crystal structure of anti-folded (E)
DMXA does not indicate any xanthenylium-anthracenolate push-pull effect. E,Z
diastereomerization of DMXA was studied by (1) H-NMR coalescence-temperature
measurements at different magnetic field strengths and by kinetic equilibration
experiments. Free energy of activation for this process was 81.5 (+/-1.3) kJ/mol.
B3LYP/6-311+G(d,p) calculations showed that anti-folded conformers of XA, (E)
DMXA, bianthrone (AA), and dixanthylene (XX) were global minima. The twisted
conformers of XA, AA, and XX were local minima (DeltaG298 = 16, 18, and 24
kJ/mol) with a substantial dipolar xanthenylium-anthracenolate dipolar
contribution for XA. Chirality 27:919-928, 2015. (c) 2015 Wiley Periodicals, Inc.
PMID- 26425785
TI - Voxel-Based Lesion Symptom Mapping of Coarse Coding and Suppression Deficits in
Patients With Right Hemisphere Damage.
AB - PURPOSE: This study examined right hemisphere (RH) neuroanatomical correlates of
lexical-semantic deficits that predict narrative comprehension in adults with RH
brain damage. Coarse semantic coding and suppression deficits were related to
lesions by voxel-based lesion symptom mapping. METHOD: Participants were 20
adults with RH cerebrovascular accidents. Measures of coarse coding and
suppression deficits were computed from lexical decision reaction times at short
(175 ms) and long (1000 ms) prime-target intervals. Lesions were drawn on
magnetic resonance imaging images and through normalization were registered on an
age-matched brain template. Voxel-based lesion symptom mapping analysis was
applied to build a general linear model at each voxel. Z score maps were
generated for each deficit, and results were interpreted using automated
anatomical labeling procedures. RESULTS: A deficit in coarse semantic activation
was associated with lesions to the RH posterior middle temporal gyrus,
dorsolateral prefrontal cortex, and lenticular nuclei. A maintenance deficit for
coarsely coded representations involved the RH temporal pole and dorsolateral
prefrontal cortex more medially. Ineffective suppression implicated lesions to
the RH inferior frontal gyrus and subcortical regions, as hypothesized, along
with the rostral temporal pole. CONCLUSION: Beyond their scientific implications,
these lesion-deficit correspondences may help inform the clinical diagnosis and
enhance decisions about candidacy for deficit-focused treatment to improve
narrative comprehension in individuals with RH damage.
PMID- 26425789
TI - Telehealth will supersede face-to-face consultations in rural Australia by 2025.
PMID- 26425790
TI - Pathways to Remote Professional Practice: New release.
PMID- 26425791
TI - Chronic disease must be confronted on two fronts.
PMID- 26425792
TI - A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and
Outcome and an Investigation of Features Associated With BRAF Mutations.
AB - IMPORTANCE: Large studies investigating clinical presentation and treatment in
primary conjunctival melanoma (CM) are rare. Clinicopathological characteristics
of BRAF-mutated CM have not been studied thoroughly. OBJECTIVES: To determine the
associations of clinicopathological tumor features and treatment with local
recurrence, metastasis, and mortality and to determine the association of BRAF
mutations with these features. DESIGN, SETTING, AND PARTICIPANTS: Population
based cohort study at the Eye Pathology Institute, Copenhagen, Denmark.
Participants included 139 patients with primary CM in Denmark from January 1,
1960, to December 31, 2012. For BRAF analysis, all patients with available
formalin-fixed, paraffin-embedded tumor samples from January 1, 1994, to December
31, 2012, were included. MAIN OUTCOMES AND MEASURES: BRAF mutations, local
recurrence, regional and distant metastasis, melanoma-related mortality, and all
cause mortality were examined. RESULTS: A poor prognosis of tumors involving the
extrabulbar conjunctiva and adjacent tissue structures was confirmed in
multivariable Cox proportional hazards regression models. Patients undergoing
incisional biopsy more frequently developed metastasis (hazard ratio [HR], 2.46;
95% CI, 1.08-5.58; P = .03). Excision without adjuvant treatment was associated
with local recurrence (HR, 1.97; 95% CI, 0.11-3.48; P = .02), metastatic disease
(HR, 2.51; 95% CI, 1.07-5.91; P = .03), and all-cause mortality (HR, 1.80; 95%
CI, 1.05-3.08; P = .03). BRAF mutations were identified in 19 of 47 primary CMs
(40.4%) and were more frequent in younger patients (P = .005), less frequent in
the extrabulbar conjunctiva (P = .05), more frequently classified as T1 tumors (P
= .03), and rarely manifested with primary acquired melanosis (P = .001) or with
a uniformly pigmented lesion (P = .006). Distant metastases developed in 6 of 19
BRAF-mutated CMs (31.6%) as opposed to 1 of 28 BRAF wild-type CMs (3.6%). No
definitive association with distant metastasis was seen in multivariable Cox
proportional hazards regression models. CONCLUSIONS AND RELEVANCE: Incisional
biopsy and excision without adjuvant therapy were associated with a poor outcome
in patients with CM. Extrabulbar location was also associated with a poor outcome
in multivariable analysis. BRAF-mutated CMs were frequent in younger patients and
were rare in tumors involving the extrabulbar conjunctiva. Despite a more
favorable location, BRAF-mutated tumors may be associated with more frequent
distant metastasis.
PMID- 26425793
TI - Learning curves for transfemoral transcatheter aortic valve replacement in the
PARTNER-I trial: Success and safety.
AB - OBJECTIVES: To identify number of cases needed to maximize device success and
minimize adverse events after transfemoral transcatheter aortic valve replacement
(TF-TAVR), and determine if adverse events were linked to the technical
performance learning curve. BACKGROUND: TF-TAVR is a complex procedure with an
incompletely characterized learning curve for clinical outcomes. METHODS: From
4/2007-2/2012, 1521 patients underwent TF-TAVR in the PARTNER-I trial. Outcomes
learning curves were defined as number of cases needed to reach a plateau for
device success, adverse events, and post-procedure length of stay. Institutional
variation was accounted for by mixed-model non-linear techniques, which were also
used to identify contribution of the procedure time learning curve to 30-day
major adverse events and length of stay. RESULTS: Eighty percent device success
was achieved after 22 cases; major vascular complications fell below 5% after 70
cases and major bleeding below 10% after 25 cases. It took an average of 28 cases
to achieve a consistent low risk of 30-day major adverse events, but institutions
entering in the middle of the trial achieved it after about 26. The most
significant correlate of 30-day major adverse events and post-procedure length of
stay was procedure time (P < 0.0001). However, this association was related to
patient and unmeasured variables, not the procedure time learning curve (P =
0.6). CONCLUSIONS: By end of trial, a consistent low risk of adverse events was
achieved after ~26 cases. However, these improved results were due to change in
patient risk profile; outcomes were not linked to the technical performance
learning curve. (c) 2015 Wiley Periodicals, Inc.
PMID- 26425794
TI - The changing importance of key factors associated with anaemia in 6- to 59-month
old children in a sub-Saharan African setting where malaria is on the decline:
analysis of the Rwanda Demographic and Health Survey 2010.
AB - OBJECTIVE: To estimate the relative contribution of malaria and other potential
determinants to current anaemia prevalence in Rwanda. METHODS: The database for
this study was the Rwanda Demographic and Health Survey 2010. Haemoglobin and
malaria test results, and additional exposures ascertained through mothers'
interviews, were analysed for all eligible children age 6-59 months (n = 4068),
in addition to diet data available for the youngest under 5-year-old per
household. We examined anaemia-exposure associations through forward logistic
regression, first for the overall population (n = 3685), and second, for the
subpopulation with diet data (n = 1934). RESULTS: In the overall study
population, malaria was strongly associated with anaemia (OR = 6.83, 95% CI: 2.90
16.05), but population impact was modest (population-attributable fraction =
2.5%). Factors associated with lower odds of anaemia were recent de-worming
medication (six months; OR = 0.60, 95% CI: 0.49-0.74), female sex (OR = 0.76, 95%
CI: 0.66-0.87), increasing age, residence in North Province and educated mother.
Being underweight and recent fever (two weeks) were associated with higher odds.
In the subpopulation with diet data, odds were lower with consumption of vitamin
A-rich foods (OR = 0.66, 95% CI: 0.50-0.88); and higher in households with many
young children. CONCLUSIONS: Malaria remains a strong determinant of anaemia for
the individual child: transmission control efforts must be maintained. At
population level, to further reduce anaemia prevalence, promoting regular vitamin
A intake from natural sources and reducing intestinal helminths burden appear the
most promising strategies to explore; exploring potential hitherto unidentified
sex-linked factors is warranted.
PMID- 26425795
TI - A prospective observational study of needle-handling practices at a University
Veterinary Teaching Hospital.
AB - AIM: To determine the period prevalence of needlestick injury (NSI) at the Massey
University Veterinary Teaching Hospital (VTH) and to identify handling and
disposal practices that may contribute to the risk of NSI. METHODS: Observations
of personnel were conducted in the equine (EVH) and companion animal (CAH)
clinics of the VTH during scheduled clinical activities over 9- and 10-day
periods, respectively. The number and type of NSI incidents, needle uncapping,
capping and disposal events were recorded for veterinarians, nurses and other
personnel (visitors and students). The number of needle-related practices, as a
proportion of observations, were compared between CAH and EVH, and veterinarians,
nurses and others using chi(2) tests. RESULTS: Needlestick injury was not
observed during 190 and 163 needle handling and disposal observations in the CAH
and EVH, respectively. Uncapping of needles by mouth was observed and was
practised more by veterinarians (15/119; 13%) than nurses (2/42; 5%) and others
(6/193; 3%) (p=0.001). Two-handed needle recapping after use was observed 265/354
times, and the one handed scooping technique was rarely observed (8/352). In the
case of needle disposal, EVH workers used a container that was not purpose built
for disposal more than CAH staff (p=0.02), or placed them in a pocket more
frequently (p=0.003). Needle disposal containers were available on adjacent bench
tops for 65/190 (34%) CAH observations, but no EVH observations. For 51/163 (31%)
EVH observations the needle disposal containers were located on the ground,
whereas none were observed there in the CAH. No approved sharps containers were
observed in the immediate EVH and CAH work areas for 47/163 (28.8%) and 1/191
(0.5%) needle-handling activities, respectively. CONCLUSIONS: Unsafe needle
handling practices must be reduced by policies and training programmes to
encourage safe needle-related practices, and ensuring that approved sharps
containers are available in close proximity to where needles are used.
PMID- 26425797
TI - A Proton-Switchable Bifunctional Ruthenium Complex That Catalyzes Nitrile
Hydroboration.
AB - A new bifunctional pincer ligand framework bearing pendent proton-responsive
hydroxyl groups was prepared and metalated with Ru(II) and subsequently isolated
in four discrete protonation states. Stoichiometric reactions with H2 and HBPin
showed facile E-H (E = H or BPin) activation across a Ru(II)-O bond, providing
access to unusual Ru-H species with strong interactions with neighboring proton
and boron atoms. These complexes were found to promote the catalytic
hydroboration of ketones and nitriles under mild conditions, and the activity was
highly dependent on the ligand's protonation state. Mechanistic experiments
revealed a crucial role of the pendent hydroxyl groups for catalytic activity.
PMID- 26425799
TI - The dysfunctional inner mirror: poor insight in obsessive-compulsive disorder,
contributions to heterogeneity and outcome.
PMID- 26425800
TI - Comorbidity of personality disorder in obsessive-compulsive disorder: special
emphases on the clinical significance.
PMID- 26425798
TI - A proteomics approach to identifying key protein targets involved in VEGF
inhibitor mediated attenuation of bleomycin-induced pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a life
expectancy of less than 5 years post diagnosis for most patients. Poor molecular
characterization of IPF has led to insufficient understanding of the pathogenesis
of the disease, resulting in lack of effective therapies. In this study, we have
integrated a label-free LC-MS based approach with systems biology to identify
signaling pathways and regulatory nodes within protein interaction networks that
govern phenotypic changes that may lead to IPF. Ingenuity Pathway Analysis of
proteins modulated in response to bleomycin treatment identified PI3K/Akt and Wnt
signaling as the most significant profibrotic pathways. Similar analysis of
proteins modulated in response to vascular endothelial growth factor (VEGF)
inhibitor (CBO-P11) treatment identified natural killer cell signaling and PTEN
signaling as the most significant antifibrotic pathways. Mechanistic/mammalian
target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) were
identified to be key mediators of pro- and antifibrotic response, where bleomycin
(BLM) treatment resulted in increased expression and VEGF inhibitor treatment
attenuated expression of mTOR and ERK. Using a BLM mouse model of pulmonary
fibrosis and VEGF inhibitor CBO-P11 as a therapeutic measure, we identified a
comprehensive set of signaling pathways and proteins that contribute to the
pathogenesis of pulmonary fibrosis that can be targeted for therapy against this
fatal disease.
PMID- 26425801
TI - Molecular identification and physiological characterization of yeasts, lactic
acid bacteria and acetic acid bacteria isolated from heap and box cocoa bean
fermentations in West Africa.
AB - Yeast, lactic acid bacteria (LAB) and acetic acid bacteria (AAB) populations,
isolated from cocoa bean heap and box fermentations in West Africa, have been
investigated. The fermentation dynamicswere determined by viable counts, and 106
yeasts, 105 LAB and 82 AAB isolateswere identified by means of rep-PCR grouping
and sequencing of the rRNA genes. During the box fermentations, the most abundant
species were Saccharomyces cerevisiae, Candida ethanolica, Lactobacillus
fermentum, Lactobacillus plantarum, Acetobacter pasteurianus and Acetobacter
syzygii, while S. cerevisiae, Schizosaccharomyces pombe, Hanseniaspora
guilliermondii, Pichia manshurica, C. ethanolica, Hanseniaspora uvarum, Lb.
fermentum, Lb. plantarum, A. pasteurianus and Acetobacter lovaniensis were
identified in the heap fermentations. Furthermore, the most abundant species were
molecularly characterized by analyzing the rep-PCR profiles. Strains grouped
according to the type of fermentations and their progression during the
transformation process were also highlighted. The yeast, LAB and AAB isolates
were physiologically characterized to determine their ability to grow at
different temperatures, as well as at different pH, and ethanol concentrations,
tolerance to osmotic stress, and lactic acid and acetic acid inhibition.
Temperatures of 45 degrees C, a pH of 2.5 to 3.5, 12% (v/v) ethanol and high
concentrations of lactic and acetic acid have a significant influence on the
growth of yeasts, LAB and AAB. Finally, the yeastswere screened for enzymatic
activity, and the S. cerevisiae, H. guilliermondii, H. uvarumand C. ethanolica
species were shown to possess several enzymes that may impact the quality of the
final product.
PMID- 26425802
TI - Variation of the Pseudomonas community structure on oak leaf lettuce during
storage detected by culture-dependent and -independent methods.
AB - The genus Pseudomonas plays an important role in the lettuce leaf microbiota and
certain species can induce spoilage. The aim of this study was to investigate the
occurrence and diversity of Pseudomonas spp. on oak leaf lettuce and to follow
their community shift during a six day cold storage with culture-dependent and
culture-independent methods. In total, 21 analysed partial Pseudomonas 16S rRNA
gene sequences matched closely (> 98.3%) to the different reference strain
sequences, which were distributed among 13 different phylogenetic groups or
subgroups within the genus Pseudomonas. It could be shown that all detected
Pseudomonas species belonged to the P. fluorescens lineage. In the culture
dependent analysis, 73% of the isolates at day 0 and 79% of the isolates at day 6
belonged to the P. fluorescens subgroup. The second most frequent group, with 12%
of the isolates, was the P. koreensis subgroup. This subgroup was only detected
at day 0. In the culture-independent analysis the P. fluorescens subgroup and P.
extremaustralis could not be differentiated by RFLP. Both groups were most
abundant and amounted to approximately 46% at day 0 and 79% at day 6. The
phytopathogenic species P. salmonii, P. viridiflava and P. marginalis increased
during storage. Both approaches identified the P. fluorescens group as the main
phylogenetic group. The results of the present study suggest that pseudomonads
found by plating methods indeed represent the most abundant part of the
Pseudomonas community on oak leaf lettuce.
PMID- 26425804
TI - Two-dimensional MoS2-assisted immediate aggregation of poly-3-hexylthiophene with
high mobility.
AB - Nanoscale morphology is of significance to the electronic properties of
semiconducting polymers. Solution-processed poly-3-hexylthiophene (P3HT) has been
demonstrated as a promising active-layer material in organic thin film
transistors (OTFTs) and solar cells. Controlling the crystallinity of P3HT chains
is critical for gaining high-performance devices. Here we demonstrated the
immediate crystallization of P3HT induced by two-dimensional MoS2 nanosheets
under ultrasonication. The resulting aggregation was attributed to the presence
of interaction between the MoS2 nanosheets and P3HT, which could enhance the
inter-chain ordering and association of P3HT. The crystallization of P3HT
contributed to the 38-fold enhancement in the hole mobility of the thin film as
compared to the non-crystallized thin films because of the absence of MoS2. Our
approach of using 2D MoS2 nanosheets to induce immediate aggregation of P3HT
provides a facile process to control the crystallization of conjugated polymers
for the development of high-performance organic electronics.
PMID- 26425803
TI - Assessing the Indirect Photochemical Transformation of Dissolved Combined Amino
Acids through the Use of Systematically Designed Histidine-Containing
Oligopeptides.
AB - Photooxidation is an important abiotic transformation pathway for amino acids
(AAs) in sunlit waters. Although dissolved free AAs are well studied, the
photooxidation of dissolved combined AAs (DCAAs) remains poorly investigated.
This study is a systematic investigation of the effect of neighboring photostable
AA residues (i.e., aliphatic, cationic, anionic, or aromatic residues) on the
environmental indirect photochemical transformation of histidine (His) in His
containing oligopeptides. The pKa values of His residues in the studied
oligopeptides were found to be between 4.3 and 8.1. Accordingly, the
phototransformation rate constants of the His-containing oligopeptides were
highly pH-dependent in an environmentally relevant pH range with higher
reactivity for neutral His than for the protonated species. The photostable AA
residues significantly modulated the photoreactivity of oligopeptides either
through altering the accessibility of His to photochemically produced oxidants or
through shifting the pKa values of His residues. In addition, the influence of
neighboring photostable AA residues on the sorption-enhanced phototransformation
of oligopeptides in solutions containing chromophoric dissolved organic matter
(CDOM) was assessed. The constituent photostable AA residues promoted sorption of
His-containing oligopeptides to CDOM macromolecules through electrostatic
attraction, hydrophobic effects, and/or low-barrier hydrogen bonds, and
subsequently increased the apparent phototransformation rate constants by up to 2
orders of magnitude.
PMID- 26425805
TI - An overview of current knowledge concerning the health and environmental
consequences of the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident.
AB - Since 2011, the scientific community has worked to identify the exact transport
and deposition patterns of radionuclides released from the accident at the
Fukushima Daiichi Nuclear Power Plant (FDNPP) in Japan. Nevertheless, there still
remain many unknowns concerning the health and environmental impacts of these
radionuclides. The present paper reviews the current understanding of the FDNPP
accident with respect to interactions of the released radionuclides with the
environment and impacts on human and non-human biota. Here, we scrutinize
existing literature and combine and interpret observations and modeling
assessments derived after Fukushima. Finally, we discuss the behavior and
applications of radionuclides that might be used as tracers of environmental
processes. This review focuses on (137)Cs and (131)I releases derived from
Fukushima. Published estimates suggest total release amounts of 12-36.7PBq of
(137)Cs and 150-160PBq of (131)I. Maximum estimated human mortality due to the
Fukushima nuclear accident is 10,000 (due to all causes) and the maximum
estimates for lifetime cancer mortality and morbidity are 1500 and 1800,
respectively. Studies of plants and animals in the forests of Fukushima have
recorded a range of physiological, developmental, morphological, and behavioral
consequences of exposure to radioactivity. Some of the effects observed in the
exposed populations include the following: hematological aberrations in Fukushima
monkeys; genetic, developmental and morphological aberrations in a butterfly;
declines in abundances of birds, butterflies and cicadas; aberrant growth forms
in trees; and morphological abnormalities in aphids. These findings are discussed
from the perspective of conservation biology.
PMID- 26425806
TI - Pre- and postnatal exposures to pesticides and neurodevelopmental effects in
children living in agricultural communities from South-Eastern Spain.
AB - BACKGROUND: Childrens exposure to neurotoxic compounds poses a major problem to
public health because oftheir actively developing brain that makes them highly
vulnerable. However, limited information is available on neuropsychological
effects in children associated with pre- and postnatal exposures to pesticides.
OBJECTIVE: To evaluate the association between current and pre- and postnatal
exposures to pesticides and their effects on neurodevelopment in children aged 6
11 years living in agricultural communities from South-Eastern Spain. METHODS: An
ambispective study was conducted on 305 children aged 6-11 years randomly
selected from public schools of the study area. Current exposure to
organophosphate pesticides was assessed measuring children's urinary levels of
dialkylphosphates (DAPs). Both prenatal and postnatal residential exposure to
pesticides was estimated by developing a geographical information system (GIS)
technology-based index that integrated distance-weighted measure of agricultural
surface, time-series of crop areas per municipality and year, and land-use maps.
Neuropsychological performance was evaluated with the Wechsler Intelligence Scale
for Children-Fourth Edition (WISC-IV). The association of pre- and postnatal and
current pesticide exposure with WISC-IV scale scores was assessed using
multivariate linear regression models and generalized estimating equation (GEE)
models, respectively. RESULTS: Greater urinary DAP levels were associated with a
poorer performance on intelligence quotient and verbal comprehension domain, with
effects being more prominent in boys than in girls. The influence of an increase
in 10 ha per year in crop surface around the child's residence during the
postnatal period was associated with decreased intelligence quotient, processing
speed and verbal comprehension scores. As regards prenatal exposure to
pesticides, a poor processing speed performance was observed. These effects were
also more prominent in boys than in girls. CONCLUSIONS: Our results suggest that
postnatal exposure to pesticides can negatively affect children's
neuropsychological performance. Prenatal exposure was weakly associated to
neurodevelopment impairment.
PMID- 26425807
TI - Exposure to long-term air pollution and road traffic noise in relation to
cholesterol: A cross-sectional study.
AB - BACKGROUND: Exposure to traffic noise and air pollution have both been associated
with cardiovascular disease, though the mechanisms behind are not yet clear.
OBJECTIVES: We aimed to investigate whether the two exposures were associated
with levels of cholesterol in a cross-sectional design. METHODS: In 1993-1997,
39,863 participants aged 50-64 year and living in the Greater Copenhagen area
were enrolled in a population-based cohort study. For each participant, non
fasting total cholesterol was determined in whole blood samples on the day of
enrolment. Residential addresses 5-years preceding enrolment were identified in a
national register and road traffic noise (Lden) were modeled for all addresses.
For air pollution, nitrogen dioxide (NO2) was modeled at all addresses using a
dispersion model and PM2.5 was modeled at all enrolment addresses using a land
use regression model. Analyses were done using linear regression with adjustment
for potential confounders as well as mutual adjustment for the three exposures.
RESULTS: Baseline residential exposure to the interquartile range of road traffic
noise,NO2 and PM2.5 was associated with a 0.58 mg/dl (95% confidence interval:
0.09; 1.25), a 0.68 mg/dl (0.22; 1.16) and a 0.78 mg/dl (0.22; 1.34) higher level
of total cholesterol in single pollutant models, respectively. In two pollutant
models with adjustment for noise in air pollution models and vice versa, the
association between air pollution and cholesterol remained for both air pollution
variables (NO2: 0.72 (0.11; 1.34); PM2.5: 0.70 (0.12; 1.28) mg/dl), whereas there
was no association for noise (-0.08mg/dl). In three-pollutant models (NO2, PM2.5
and road traffic noise), estimates for NO2 and PM2.5 were slightly diminished
(NO2: 0.58 (-0.05; 1.22); PM2.5: 0.57 (-0.02; 1.17) mg/dl). CONCLUSIONS: Air
pollution and possibly also road traffic noise may be associated with slightly
higher levels of cholesterol, though associations for the two exposures were
difficult to separate.
PMID- 26425809
TI - Chelating Surfaces for Native State Proteins Patterning: The Human Serum Albumin
Case.
AB - The paper reports a new "soft" surface functionalization strategy, based on a
highly selective ion metal chelation process. The proposed stepwise methodology
implies at first the construction of a monolayer of terpyridine-based thiol
(Tpy), whose highly packed structuring has been followed in situ by using quartz
crystal microbalance (QCM-D) measurements, showing that the monolayers consist of
about 2.7 * 10(14) Tpy/cm(2). Then, the tridentate sites of the each Tpy moiety
are employed to partially chelate divalent metal ions, providing an effective
platform to anchoring proteins by completing the metal ion coordination with an
available site on the protein of interest. We report the case study of the
application of the process to the HSA immobilization onto various surfaces,
including Tpy-Fe(II) and Tpy-Cu(II) complexes, as well as hydrophilic bare gold
substrates and hydrophobic self-assembled Tpy-based monolayers. It is shown that
the chelation interaction between Tpy-Cu(II) complexes and HSA produces the
highest and most robust HSA immobilization, with an adsorbed mass at the steady
state of ~800 ng/cm(2), with respect to an average adsorption of ~350 ng/cm(2)
for the other surfaces. Furthermore, Cu(II)-chelated surfaces seem to promote a
sort of protein "soft" landing, preventing the ubiquitous surface-induced major
unfolding and transmitting an orientation information to the protein, owing to
the highly specific symmetry coordination of the Tpy-Cu(II)-protein complex.
Indeed, the interaction with a specific monoclonal antiboby (anti-HSA) indicated
the lack of a significant protein denaturation, while a massive
reorientation/denaturation process was found for all the remaining surfaces,
including the Tpy-Fe(II) complex. Finally, the metal-ion-dependent HSA
immobilization selectivity has been exploited to obtain micropatterned surfaces,
based on the strikingly different strength of interaction and stability observed
for Fe(II) and Cu(II) complexes.
PMID- 26425810
TI - One-pot synthesis of cobalt-coordinated N-doped carbon catalysts via co-synthesis
of ionic liquids and cobalt porphyrins.
AB - Cobalt-coordinated N-doped carbon (CoNC) was fabricated by heating cobalt
porphyrins and ionic liquids. The prepared catalysts displayed superior catalytic
capacity for the direct oxidation of ethylbenzene, and unprecedented stability
was obtained even after six runs with a similar catalytic performance.
PMID- 26425808
TI - Using a 3D Culture System to Differentiate Visceral Adipocytes In Vitro.
AB - It has long been recognized that body fat distribution and regional adiposity
play a major role in the control of metabolic homeostasis. However, the ability
to study and compare the cell autonomous regulation and response of adipocytes
from different fat depots has been hampered by the difficulty of inducing
preadipocytes isolated from the visceral depot to differentiate into mature
adipocytes in culture. Here, we present an easily created 3-dimensional (3D)
culture system that can be used to differentiate preadipocytes from the visceral
depot as robustly as those from the sc depot. The cells differentiated in these
3D collagen gels are mature adipocytes that retain depot-specific
characteristics, as determined by imaging, gene expression, and functional
assays. This 3D culture system therefore allows for study of the development and
function of adipocytes from both depots in vitro and may ultimately lead to a
greater understanding of site-specific functional differences of adipose tissues
to metabolic dysregulation.
PMID- 26425811
TI - Rapid, specific, simple, in-field detection of Xanthomonas campestris pathovar
musacearum by loop-mediated isothermal amplification.
AB - AIMS: To develop and evaluate a loop-mediated isothermal amplification (LAMP)
assay for Xanthomonas campestris pathovar musacearum (Xcm), the causal agent of
banana Xanthomonas wilt, a major disease of banana in Africa. METHODS AND
RESULTS: LAMP primers were designed to the general secretion pathway protein D
gene and tested against 17 isolates of Xcm encompassing the known genetic and
geographic diversity of the bacterium and all isolates were detected. Seventeen
other Xanthomonas isolates, including closely related Xanthomonas vasicola, other
bacterial pathogens/endophytes of Musa and two healthy Musa varieties gave
negative results with the LAMP assay. The assay showed good sensitivity,
detecting as little as 51 fg of Xcm DNA, a greater level of sensitivity than that
of an Xcm PCR assay. Amplification with the LAMP assay was very rapid, typically
within 9 min from bacterial cultures. Symptomatic field samples of Musa from
Uganda were tested and all produced amplification in less than 13 min.
CONCLUSIONS: The LAMP assay provides rapid, sensitive detection of the pathogen
that is ideally suited for deployment in laboratories with basic facilities and
in-field situations. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first LAMP
assay for Xcm which provides a significant improvement compared to existing
diagnostics.
PMID- 26425812
TI - Randomized controlled multicenter study comparing short dental implants (6 mm)
versus longer dental implants (11-15 mm) in combination with sinus floor
elevation procedures. Part 2: clinical and radiographic outcomes at 1 year of
loading.
AB - AIM: To compare, clinically and radiographically, short dental implants (6 mm) to
long implants (11-15 mm) placed with sinus grafting. METHODS: Participants with 5
7 mm of bone height in the posterior maxilla were randomly allocated to receive
short implants (GS) or long implants with sinus grafting (GG). Implants were
loaded with single crowns 6 months after placement (PR). Patients were re
evaluated 12 months after loading (FU-1). Outcome variables included: Implant
survival rate (CSR), marginal bone level alteration (MBL), periodontal probing
depth (PPD), bleeding on probing (BoP), plaque control record (PCR) and crown-to
implant ratios (C/I). Statistical analysis was performed using parametric tests.
RESULTS: In 97 subjects, 132 implants were re-evaluated at FU-1. The CSR was
100%. The MBL from implant placement (IP) to (PR) was -0.22 +/- 0.4 mm for GG and
-0.3 +/- 0.45 mm for GS (p < 0.001). MBL from IP to FU-1 was -0.37 +/- 0.59 mm
for GG and -0.22 +/- 0.3 mm for GS (p < 0.001). Intergroup comparisons showed non
significant differences for MBL (p > 0.05), PPD (p = 1) and PCR (p = 0.09). BoP
was higher in the GS (p = 0.04). The C/I was 0.99 +/- 0.17 for GG and 1.86 +/-
0.23 for GS (p < 0.001). No correlation was observed between C/I and MBL, (GG: p
= 0.13; GS: p = 0.38). CONCLUSIONS: Both treatment modalities provided similar
outcomes.
PMID- 26425817
TI - Lipophilic M(alpha,alpha'-OC5H11)8phthalocyanines (M = H2 and Ni(II)): synthesis,
electronic structure, and their utility for highly efficient carbonyl reductions.
AB - A lipophilic and electron-rich phthalocyanine (alpha,alpha'-n-OC5H11)8-H2Pc and
its nickel(ii) complex (alpha,alpha'-n-OC5H11)8-Ni(ii)Pc have been synthesized
and characterized. Detailed analyses of the electronic structure were carried out
by spectroscopy, electrochemistry, spectroelectrochemistry, and TD-DFT
calculations. A series of experiments demonstrate that the (alpha,alpha'-n
OC5H11)8-Ni(ii)Pc complex can be used as a catalyst for highly efficient carbonyl
reductions.
PMID- 26425818
TI - The HOMO Nodal Arrangement in Polychromophoric Molecules and Assemblies Controls
the Interchromophoric Electronic Coupling.
AB - Triptycenes spontaneously assemble into two-dimensional networks in which long
range charge transport is facilitated by the extensive electronic coupling
through the triptycene framework (intramolecularly) and by cofacial pi-stacking
(intermolecularly). While designing and synthesizing next-generation triptycenes
containing polyaromatic chromophores, the electronic coupling amongst the
chromophores was observed to be highly dependent on the nature and position of
the substituents. Herein, we demonstrate using hexaalkoxytriptycenes that the
electronic coupling amongst the chromophores is switched on and off by a simple
repositioning of the substituents, which alters the nodal arrangement of the
HOMOs of the individual chromophores. A visual inspection of the HOMOs can thus
provide a ready evaluation of the electronic coupling in polychromophoric
molecules/assemblies, and will serve as an important tool for the rational design
of modern charge-transport materials.
PMID- 26425819
TI - Isolation of cytotoxic diterpenoids from the Chilean medicinal plant Azorella
compacta Phil from the Atacama Desert by high-speed counter-current
chromatography.
AB - BACKGROUND: Azorella compacta (Apiaceae) is a native Chilean cushion shrub which
produces a resin containing mulinane and azorellane diterpenoids. This plant has
been used since pre-Colombian times to treat inflammation and dental neuralgias.
In this work the first preparative fractionation of diterpenoids present in this
plant by means of high-speed counter-current chromatography (HSCCC) was applied,
and cytotoxic effects of the isolated compounds were evaluated for the first time
against a panel of MCF7 cells. RESULTS: The major compounds isolated were
identified by means of spectroscopy as azorellanol, 13alpha, 14alpha
dihydroxymulin-11-en-20-oic acid, mulinolic acid, mulin-11,13-dien-20-oic acid,
17-acetoxy-mulin-11,13-dien-20 oic acid, and 17-acetoxy-mulinic acid (compounds
7, 9-11 and 13, respectively), and four minor diterpenoids [7-deacetyl
azorellanol (6), 13-epi-azorellanol, 7-acetoxy-mulin-9,12-diene, and 17-acetoxy
mulin-11,13-dien-20-oic acid (compounds 4, 8 and 12)], together with three new
minor diterpenoids: 13beta,14beta-dihydroxymulin-11-en-20-oic acid (1), 13
epiazorellanone (2) and 13-epi-7-deacetyl-azorellanol (3) were identified.
Besides, compounds 4, 6, 7, 8 and 11 displayed good cytotoxic activity (less than
50% cell viability at 100 uM). Among them, compound 7, an acetylated azorellane,
was the most active. CONCLUSIONS: HSCCC allowed the isolation of 13 diterpenoids
present in A. compacta. Three compounds are reported for the first time. Isolated
azorellanes are more potent cytotoxic agents than are mulinanes. (c) 2015 Society
of Chemical Industry.
PMID- 26425821
TI - Making the case for collaboration.
PMID- 26425822
TI - Understanding the effects of rheumatoid arthritis.
PMID- 26425820
TI - Interferon-gamma constrains cytokine production of group 2 innate lymphoid cells.
AB - Group 2 innate lymphoid cells (ILC2s) produce a significant amount of interleukin
5 (IL-5), which supports eosinophil responses in various tissues; they also
produce IL-13, which induces mucus production and contributes to tissue repair or
fibrosis. The ILC2s are activated by alarmins, such as IL-33 released from
epithelia, macrophages and natural killer T (NKT) cells in response to infection
and allergen exposure, leading to epithelial injury. We examined gene expression
in lung ILC2s and found that ILC2s expressed Ifngr1, the receptor for interferon
gamma (IFN-gamma). Interferon-gamma severely inhibited IL-5 and IL-13 production
by lung and kidney ILC2s. To evaluate the effects in vivo, we used alpha
galactosylceramide (alpha-GalCer) to induce NKT cells to produce IL-33 and IFN
gamma. Intraperitoneal injection of alpha-GalCer in mice induced NKT cell
activation resulting in IL-5 and IL-13 production by ILC2s. Administration of
anti-IFN-gamma together with alpha-GalCer significantly enhanced the production
of IL-5 and IL-13 by ILC2s in lung and kidney. Conversely, cytokine production
from ILC2s was markedly suppressed after injection of exogenous IL-33 in Il33(-/
) mice pre-treated with alpha-GalCer. Hence, IFN-gamma induced or already present
in tissues can impact downstream pleiotropic functions mediated by ILC2s, such as
inflammation and tissue repair.
PMID- 26425823
TI - The role of illness perceptions in adherence to surveillance in patients with
familial adenomatous polyposis (FAP).
AB - OBJECTIVE: The aim of the study was to examine patients' beliefs about having
familial adenomatous polyposis (FAP), a hereditary colorectal cancer syndrome,
and how these beliefs are associated with adherence to endoscopic surveillance.
METHODS: Adult patients diagnosed with FAP on the national Swedish polyposis
register who had undergone prophylactic colorectal surgery (n 209, response rate
76%) completed the Illness Perception Questionnaire (IPQ). Logistic regression
analysis was used to investigate the relationships between illness perceptions
and adherence, when controlling for demographic and clinical factors. RESULTS:
FAP was less distressing in men and those with fewer symptoms, reporting less
serious consequences and more coherent understanding of FAP. Non-adherence (14%)
to surveillance was associated with being older, having undergone surgery less
recently and no history of malignancy. Patients' beliefs about their FAP were
able to explain unique variance in non-adherence, in particular those who
believed FAP was less distressing. CONCLUSIONS: Patients who were non-adherent to
endoscopic surveillance had more positive perceptions about their FAP and, in
particular, were less emotionally affected compared to those who adhered. As non
adherence implies a greater risk of future malignancies, special efforts are
required to effectively prevent cancer in all patients with FAP. Those who have
lived with the condition for a long time, and are not troubled by
gastrointestinal symptoms or worried about their FAP, may be in need of specific
information and support. Further prospective research is required to examine
emotional predictors and consequences of non-adherence. Copyright (c) 2015 John
Wiley & Sons, Ltd.
PMID- 26425824
TI - Rhodium-catalyzed Asymmetric Hydrogenation of alpha-Dehydroamino Ketones: A
General Approach to Chiral alpha-amino Ketones.
AB - Rhodium/DuanPhos-catalyzed asymmetric hydrogenation of aliphatic alpha
dehydroamino ketones has been achieved and afforded chiral alpha-amino ketones in
high yields and excellent enantioselectives (up to 99 % ee), which could be
reduced further to chiral beta-amino alcohols by LiAlH(tBuO)3 with good yields.
This protocol provides a readily accessible route for the synthesis of chiral
alpha-amino ketones and chiral beta-amino alcohols.
PMID- 26425825
TI - Phase-Separation-Induced Anomalous Stiffening, Toughening, and Self-Healing of
Polyacrylamide Gels.
AB - Novel, tough, strong, and self-healable poly-acrylamide (PAAm) gels are
fabricated by inducing an appropriate phase-separation structure using a poor
solvent. The phase separation induces a gel-glass-like transition of the PAAm
gels, providing the gels an anomalously high modulus (211 MPa), fracture stress
(7.13 MPa), and fracture energy (4.16 * 10(4) J m(-2)), while keeping a high
solvent content (~60 vol%).
PMID- 26425826
TI - Micro-optical coherence tomography tracking of magnetic gene transfection via Au
Fe3O4 dumbbell nanoparticles.
AB - Heterogeneous Au-Fe3O4 dumbbell nanoparticles (NPs) are composed of Au NPs and
Fe3O4 NPs that bring in optical and magnetic properties respectively. This
article reports the engineering of Au-Fe3O4 NPs as gene carriers for magnetic
gene transfection as well as contrast agents for micro-optical coherence
tomography (MUOCT). As a proof-of-concept, Au-Fe3O4 NPs are used to deliver the
green fluorescent protein to HEK 293T cells and their entrance into the cells is
monitored through MUOCT.
PMID- 26425828
TI - Brain sonography insight into the midbrain in myotonic dystrophy type 2.
AB - INTRODUCTION: The aim of this study was to analyze transcranial sonography (TCS)
findings in genetically confirmed myotonic dystrophy type 2 (DM2) patients.
METHODS: Forty DM2 patients and 38 gender- and age-matched healthy controls (HCs)
underwent TCS through the pre-auricular acoustic bone window. RESULTS: Substantia
nigra hyperechogenicity was found in 20% of DM2 patients compared with 3% of HCs.
Brainstem raphe (BR) hypoechogenicity was more common in DM2 patients compared
with HCs (56% vs. 10%, P < 0.01), and it was more common in patients with fatigue
and excessive daytime sleepiness (P < 0.05). Diameter of the third ventricle was
increased in DM2 patients compared with HCs (5.8 +/- 1.7 vs. 5.1 +/- 1.0 mm, P <
0.05). CONCLUSIONS: Finding BR hypoechogenicity might have clinical implication
because of the potential response to serotonin-reuptake inhibitors. TCS revealed
alterations in brain structures previously not seen in MRI studies.
PMID- 26425827
TI - Retinol binding protein and vitamin D associations with serum antibody isotypes,
serum influenza virus-specific neutralizing activities and airway cytokine
profiles.
AB - Vitamin A supports the induction of immunoglobulin (Ig)A responses at mucosal
surfaces in mice, but much less is known about the influence of vitamins on
antibody isotype expression in humans. To address this knowledge gap, we examined
46 residual blood samples from adults and children, some of whom were
experiencing influenza virus infections of the respiratory tract. Assays were
performed for retinol binding protein (RBP, a surrogate for vitamin A), vitamin D
(a related vitamin) and antibody isotypes. Results showed that all but two tested
samples exhibited RBP and/or vitamin D insufficiencies or deficiencies. Vitamin D
correlated with blood IgM and IgG3, while RBP correlated with IgG4 and IgA. RBP
also correlated positively with age and with influenza virus-specific antibody
neutralization titres. Individuals with low blood RBP levels exhibited the
highest frequencies of over-expressed cytokines and growth factors in nasal wash
samples, an indication of inflamed mucosal tissues. While cause-effect
relationships were not discerned, results support a hypothesis that vitamins
directly influence B cell isotype expression in humans, and by so doing may help
protect mucosal surfaces from respiratory viral disease.
PMID- 26425830
TI - The SUDEP Risk Inventory: Association with postictal generalized EEG suppression.
AB - To help identify patients at greatest risk for sudden unexpected death in
epilepsy (SUDEP), screening inventories like the SUDEP-7 Inventory can be useful.
In this study, we examined the strength of association between this inventory's
risk factors and postictal generalized EEG suppression (PGES), a biomarker of
SUDEP risk. We reanalyzed data from an epilepsy monitoring unit study of 37
children. We performed a 2 by 2 contingency table analysis to determine the
association between "yes" responses on the inventory questions and PGES following
>=1 seizure. Having a history of >3 generalized tonic-clonic seizures (GTCS) in
the past year had the strongest association with PGES (Pearson chi-square
p<0.001, Cramer's V=0.75). Having >=1 GTCS in the past year was also strongly
associated with PGES (Pearson chi-square p<0.001, Cramer's V=0.636). Histories of
>50 seizures of any type/month (Pearson chi-square p=0.14, Cramer's V=0.241) and
intellectual disability (Pearson chi-square p=0.04, Cramer's V=0.337) were not as
robustly associated with PGES. Current use of >=3 AEDs had the weakest
association with PGES (Pearson chi-square p=0.66, Cramer's V=0.072). Given that
all study patients had >=1 seizure per year and epilepsy durations <30 years, the
strength of association with these questions and PGES could not be analyzed.
PMID- 26425829
TI - Volumetric and shape analysis of hippocampal subfields in unilateral mesial
temporal lobe epilepsy with hippocampal atrophy.
AB - OBJECTIVE: The hippocampus consists of several functionally and histologically
different subfields that are known to be differentially affected in mesial
temporal lobe epilepsy with hippocampal sclerosis (MTLE). Using automated MRI
analyses, we aimed to investigate atrophy patterns of hippocampal subfields and
their relationships with clinical characteristics in a homogenous group of
unilateral MTLE. METHODS: Twenty-four left MTLE patients, 23 right MTLE patients,
and 41 control subjects were scanned on a 3T MR scanner. Automated volumetry and
shape analysis were used to assess volume and shape changes of hippocampal
subfields in MTLE patients relative to controls. Within-group correlations were
performed between subfield volumes and clinical variables in patients. RESULTS:
Compared to controls, left and right MTLE patients exhibited significant volume
reductions in ipsilateral whole hippocampus and subfields including CA1, CA2-3,
CA4-DG, presubiculum, and subiculum (corrected p<0.05). Regional inward shape
deformation mainly localized to ipsilateral CA1 and adjacent subiculum was found
in left and right MTLE patients relative to controls (corrected p<0.05). Longer
disease duration was related to smaller volumes of left CA1, presubiculum, and
subiculum in left MTLE, and right CA1 in right MTLE. CONCLUSION: We found overall
volume reductions in ipsilateral hippocampal subfields in patients with
unilateral MTLE, in accordance with known pathologic findings. Our findings of
regional atrophy in ipsilateral CA1 and subiculum on shape analysis and an
inverse relationship between disease duration and ipsilateral CA1 volume
implicate an important role of CA1 and subiculum in the pathogenesis underlying
MTLE.
PMID- 26425831
TI - Predicting toxicity to Hyalella azteca in pyrogenic-impacted sediments-Do we need
to analyze for all 34 PAHs?
AB - Polycyclic aromatic hydrocarbons (PAHs) are major drivers of risk at many urban
and/or industrialized sediment sites. The US Environmental Protection Agency
(USEPA) currently recommends using measurements of 18 parent + 16 groups of
alkylated PAHs (PAH-34) to assess the potential for sediment-bound PAHs to impact
benthic organisms at these sites. ASTM Method D7363-13 was developed to directly
measure low-level sediment porewater PAH concentrations. These concentrations are
then compared to ambient water criteria (final chronic values [FCVs]) to assess
the potential for impact to benthic organisms. The interlaboratory validation
study that was used to finalize ASTM D7363-13 was developed using 24 of the 2-, 3
, and 4-ring PAHs (PAH-24) that are included in the USEPA PAH-34 analyte list.
However, it is the responsibility of the user of ASTM Method D7363 to establish a
test method to quantify the remaining 10 higher molecular weight PAHs that make
up PAH-34. These higher molecular weight PAHs exhibit extremely low saturation
solubilities that make their detection difficult in porewater, which has proven
difficult to implement in a contract laboratory setting. As a result, commercial
laboratories are hesitant to conduct the method on the entire PAH-34 analyte
list. This article presents a statistical comparison of the ability of the PAH-24
and PAH-34 porewater results to predict survival of the freshwater amphipod
Hyalella azteca, using the original 269 sediment samples used to gain ASTM D7363
Method approval. The statistical analysis shows that the PAH-24 are statistically
indistinguishable from the PAH-34 for predicting toxicity. These results indicate
that the analysis of freely dissolved porewater PAH-24 is sufficient for making
risk-based decisions based on benthic invertebrate toxicity (survival and
growth). This reduced target analyte list should result in a cost-saving for
stakeholders and broader implementation of the method at PAH-impacted sediment
sites. Integr Environ Assess Manag 2016;12:493-499. (c) 2015 SETAC.
PMID- 26425832
TI - Lifestyle and therapeutic interventions for hypertension.
PMID- 26425833
TI - Salutary cardiovascular effects of antidiabetic drugs: myth or fact?
PMID- 26425834
TI - Where there's smoke there might be hypertension.
PMID- 26425835
TI - Updated classification of hypertensive retinopathy: which role for cardiovascular
risk stratification?
PMID- 26425836
TI - Night-time blood pressure and target organ damage: a comparative analysis of
absolute blood pressure and dipping status.
AB - BACKGROUND: The prognostic significance of abnormal circadian blood pressure (BP)
patterns is well established. Research to date has focused on both nocturnal
dipping and absolute night-time BP levels; however, which of these variables
should be the primary target for therapy remains unclear. The aim of this study
is to determine whether dipping status or absolute night-time BP levels have a
stronger association with subclinical target organ damage (TOD). METHODS: The
Mitchelstown Cohort was established to examine cardiovascular health in an adult
population sample recruited from primary care. Night-time BP was categorized by
dipping status. Subclinical TOD was defined as Cornell Product left ventricular
hypertrophy (LVH) voltage criteria on ECG and urine albumin : creatinine ratio
(ACR) at least 1.1 mg/mmol. Multivariable logistic regression analysis was used
to assess the association between night-time BP and TOD. RESULTS: Of 2047
participants, 1207 (response rate 59%), underwent 24-h ambulatory BP monitoring.
We excluded 161 studies due to incomplete data. Of 1046 participants, 178 (17%)
had evidence of TOD. Each 10-mmHg rise in night-time SBP increased the odds of
TOD. Odds ratio (OR) ACR at least 1.1 mg/mmol 1.5 [95% confidence interval (95%
CI) 1.2-1.8] and OR LVH 1.4 (95% CI 1.1-1.8). CONCLUSION: Absolute BP level
rather than dipping status may be a superior early marker of risk associated with
night-time BP. Interventional studies are required to determine whether there is
a benefit in specifically targeting absolute night-time BP levels to prevent
clinically important outcomes.
PMID- 26425837
TI - PTPRD gene associated with blood pressure response to atenolol and resistant
hypertension.
AB - OBJECTIVE: The aim of this study is to identify single-nucleotide polymorphisms
(SNPs) influencing blood pressure (BP) response to the beta-blocker atenolol.
METHODS: Genome-wide association analysis of BP response to atenolol monotherapy
was performed in 233 white participants with uncomplicated hypertension in the
pharmacogenomic evaluation of antihypertensive responses study. Forty-two
polymorphisms with P less than 10 for association with either diastolic or
systolic response to atenolol monotherapy were validated in four independent
groups of hypertensive individuals (total n = 2114). RESULTS: In whites, two
polymorphisms near the gene PTPRD (rs12346562 and rs1104514) were associated with
DBP response to atenolol (P = 3.2 * 10 and P = 5.9 * 10, respectively) with
directionally opposite association for response to hydrochlorothiazide in another
group of 228 whites (P = 0.0018 and P = 0.00012). A different polymorphism
(rs10739150) near PTPRD was associated with response to atenolol in 150 black
hypertensive individuals (P = 8.25 * 10). rs12346562 had a similar trend in
association with response to bisoprolol (a different beta-blocker) in 207 Finnish
men in the genetics of drug responsiveness in essential hypertension study. In
addition, an intronic single-nucleotide polymorphism (rs4742610) in the PTPRD
gene was associated with resistant hypertension in whites and Hispanics in the
international verapamil SR trandolapril study (meta-analysis P = 3.2 * 10).
CONCLUSION: PTPRD was identified as a novel locus potentially associated with BP
response to atenolol and resistant hypertension in multiple ethnic groups.
PMID- 26425839
TI - Alkene anti-Dihydroxylation with Malonoyl Peroxides.
AB - Malonoyl peroxide 1, prepared in a single step from the commercially available
diacid, is an effective reagent for the anti-dihydroxylation of alkenes. Reaction
of 1 with an alkene in the presence of acetic acid at 40 degrees C followed by
alkaline hydrolysis leads to the corresponding diol (35-92%) with up to 13:1 anti
selectivity. A mechanism consistent with experimental findings is proposed that
accounts for the selectivity observed.
PMID- 26425838
TI - Parasite molecules and host responses in cystic echinococcosis.
AB - Cystic echinococcosis is the infection by the larvae of cestode parasites
belonging to the Echinococcus granulosus sensu lato species complex. Local host
responses are strikingly subdued in relation to the size and persistence of these
larvae, which develop within mammalian organs as 'hydatid cysts' measuring up to
tens of cm in diameter. In a context in which helminth-derived immune
suppressive, as well as Th2-inducing, molecules garner much interest, knowledge
on the interactions between E. granulosus molecules and the immune system lags
behind. Here, we discuss what is known and what are the open questions on E.
granulosus molecules and structures interacting with the innate and adaptive
immune systems, potentially or in demonstrated form. We attempt a global
biological approach on molecules that have been given consideration primarily as
protective (Eg95) or diagnostic antigens (antigen B, antigen 5). We integrate
glycobiological information, which traverses the discussions on antigen 5, the
mucin-based protective laminated layer and immunologically active preparations
from protoscoleces. We also highlight some less well-known molecules that appear
as promising candidates to possess immune-regulatory activities. Finally, we
point out gaps in the molecular-level knowledge of this infectious agent that
hinder our understanding of its immunology.
PMID- 26425840
TI - Metabolic profile of phillyrin in rats obtained by UPLC-Q-TOF-MS.
AB - Forsythia suspensa Vahl (Oleaceae) is an important original plant in traditional
Chinese medicine. The air-dried fruits of Forsythia suspensa have long been used
to relieve respiratory symptoms. Phillyrin is one of the main chemical
constituent of Forsythia suspensa. A clear understanding of the metabolism of
phillyrin is very important in rational clinical use and pharmacological
research. In this study, the metabolism of phillyrin in rat was investigated for
the first time using an ultra-high-performance liquid chromatography quadrupole
time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method. Bile, urine and feces
were collected from rats after single-dose (10 mg/kg) orally administered
phillyrin. Liquid-liquid extraction and ultrasonic extraction were used to
prepare samples. UPLC-Q-TOF-MS analysis of the phillyrin samples showed that
phillyrin was converted to a major metabolite, M26, which underwent
deglucosidation, further dehydration and desaturation. A total of 34 metabolites
were detected including 30 phase I and four phase II metabolites. The conjugation
types and structure skeletons of the metabolites were preliminarily determined.
Moreover, 28 new metabolites were reported for the first time. The main
biotransformation route of phillyrin was identified as hydrolysis, oxidation and
sulfation. These findings enhance our understanding of the metabolism and the
real active structures of phillyrin. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26425841
TI - Does lymphopenia or macrocytosis reflect 6-thioguanine levels in patients with
inflammatory bowel disease treated with azathioprine or 6-mercaptopurine?
AB - BACKGROUND: The thiopurine drugs, 6-mercaptopurine and azathioprine, remain the
mainstay of immunomodulator therapy for inflammatory bowel disease (IBD). Optimal
management depends on achieving therapeutic levels of 6-thioguanine (6-TGN), but
measuring thiopurine metabolites is associated with significant cost. Thiopurines
cause lymphopenia and an increase in mean corpuscular volume (MCV). It is unclear
whether any clinically useful correlation exists between 6-TGN levels and
lymphocyte count or MCV. AIMS: The aim of this study is to investigate the
correlation between 6-TGN levels and lymphocyte count and MCV in thiopurine
treated patients with IBD. METHODS: We analysed a prospectively acquired database
of 67 patients with IBD treated with thiopurine therapy. The data were analysed
looking at the relationship between 6-TGN levels and both lymphocyte count and
MCV by using the Spearman's rank correlation coefficient. RESULTS: Twenty-seven
(40%) patients had therapeutic 6-TGN levels. Thirty-three (49%) patients had sub
therapeutic 6-TGN levels. A weak positive correlation between 6-TGN levels and
lymphocyte count was demonstrated, but this was not statistically significant
(Spearman's R = 0.14, P = 0.23). Spearman's rank correlation coefficient between
6-TGN levels and MCV was statistically significant (R = 0.42, P = 0.0005). MCV
>101 fL excluded a subtherapeutic 6-TGN level with positive predictive value of
92%. CONCLUSIONS: There is no specific lymphopenia that can be assumed to
indicate a therapeutic 6-TGN level. The relationship between 6-TGN levels and MCV
is likely to be clinically relevant. If MCV is elevated, 6-TGN is unlikely to be
sub-therapeutic. MCV is a potential surrogate marker which can rule out sub
therapeutic thiopurine metabolites in patients with IBD treated with azathioprine
or 6-mercaptopurine.
PMID- 26425842
TI - Kidney Paired Donation Protocol for Participating Donors 2014.
PMID- 26425843
TI - Smooth Muscle Cell Differentiation: Model Systems, Regulatory Mechanisms, and
Vascular Diseases.
AB - Smooth muscle cell (SMC) differentiation is an important process during vascular
development. The highly differentiated mature SMCs play critical roles in
maintaining structural and functional integrity of blood vessels. However, SMCs
are not terminally differentiated, and their phenotype can be modulated between
contractile and proliferative states in response to various environmental
conditions. Alterations in SMC phenotype contribute to a number of major
cardiovascular diseases such as atherosclerosis, hypertension and restenosis
following angioplasty, etc. The goal of this review is to provide a brief
overview of the recent advancements in our understanding of SMC differentiation
and the development of in vitro SMC differentiation models, with a particular
emphasis on examination of molecular mechanisms involved in the regulation of SMC
differentiation and phenotypic modulation. J. Cell. Physiol. 231: 777-787, 2016.
(c) 2015 Wiley Periodicals, Inc.
PMID- 26425844
TI - Therapeutic Potential of Date Palm Pollen for Testicular Dysfunction Induced by
Thyroid Disorders in Male Rats.
AB - Hyper- or hypothyroidism can impair testicular function leading to infertility.
The present study was designed to examine the protective effect of date palm
pollen (DPP) extract on thyroid disorder-induced testicular dysfunction. Rats
were divided into six groups. Group I was normal control. Group II received oral
DPP extract (150 mg kg(-1)), group III (hyperthyroid group) received
intraperitoneal injection of L-thyroxine (L-T4, 300 MUg kg(-1); i.p.), group IV
received L-T4 plus DPP extract, group V (hypothyroid group) received
propylthiouracil (PTU, 10 mg kg(-1); i.p.) and group VI received PTU plus DPP
extract. All treatments were given every day for 56 days. L-T4 or PTU lowered
genital sex organs weight, sperm count and motility, serum levels of luteinizing
hormone (LH), follicle stimulating hormone (FSH) and testosterone (T), testicular
function markers and activities of testicular 3beta-hydroxysteroid dehydrogenase
(3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). Moreover, L-T4
or PTU increased estradiol (E2) serum level, testicular oxidative stress, DNA
damage and apoptotic markers. Morphometric and histopathologic studies backed
these observations. Treatment with DPP extract prevented LT4- or PTU induced
changes. In addition, supplementation of DPP extract to normal rats augmented
sperm count and motility, serum levels of LH, T and E2 paralleled with increased
activities of 3beta-HSD and 17beta-HSD as well as testicular antioxidant status.
These results provide evidence that DPP extract may have potential protective
effects on testicular dysfunction induced by altered thyroid hormones.
PMID- 26425845
TI - Addressing the Complications of Ebola and Other Viral Hemorrhagic Fever
Infections: Using Insights from Bacterial and Fungal Sepsis.
PMID- 26425846
TI - Glaucomatous-Type Optic Discs in High Myopia.
AB - PURPOSE: To assess the prevalence of glaucoma in patients with high myopia
defined as myopic refractive error of >-8 diopters or axial length >=26.5 mm.
METHODS: The hospital-based observational study included 172 patients (336 eyes)
with a mean age of 61.9+/-12.3 years and mean axial length of 30.1+/-2.3 mm
(range: 24.7-39.1mm). Glaucomatous-type optic discs were defined by glaucomatous
optic disc appearance. Glaucoma was defined by glaucomatous optic disc appearance
and glaucomatous Goldmann visual field defects not corresponding with myopic
macular changes. RESULTS: Larger disc area (mean: 3.18+/-1.94 mm2) was associated
with longer axial length (P<0.001; standardized correlation coefficient: 0.45).
Glaucoma was detected in 94 (28%; 95% Confidence intervals: 23%, 33%) eyes. In
multivariate analysis, glaucoma prevalence was 3.2 times higher (P<0.001) in
megalodiscs (>3.79 mm2) than in normal-sized discs or small discs (<1.51 mm2)
after adjusting for older age. Axial length was not significantly (P = 0.38)
associated with glaucoma prevalence in that model. Glaucoma prevalence increased
by a factor of 1.39 for each increase in optic disc area by one mm2. Again, axial
length was not significantly (P = 0.38) associated with glaucoma prevalence when
added to this multivariate model. CONCLUSION: Within highly myopic individuals,
glaucoma prevalence increased with larger optic disc size beyond a disc area of
3.8 mm2. Highly myopic megalodiscs as compared to normal sized discs or small
discs had a 3.2 times higher risk for glaucomatous optic nerve neuropathy. The
increased glaucoma prevalence in axial high myopia was primarily associated with
axial myopia associated disc enlargement and not with axial elongation itself.
PMID- 26425848
TI - Waist circumference cut-off in relation to body mass index and percentage of body
fat in adult women from Merida, Mexico.
AB - Waist circumference (WC) as an index of central obesity is related to body mass
index (BMI) and percent body fat (PBF). Waist circumference data were analyzed to
identify a WC cut-off for adult women with respect to BMI-based obesity (>= 30
kg/m2) and PBF. The sample was 138 women aged 22 to 41 years with Maya ancestry
(based on surnames) in Merida, Yucatan, measured during 2011 - 2013.
Anthropometric parameters included height, body weight (BW), and BMI. The PBF was
estimated by bioelectrical impedance. Estimated cut-offs per centimeter WC (80 -
99 cm) were predicted by BMI for obesity (>= 30 kg m-2; binomial: Yes = 1, No =
0) and PBF (continuous variable) using binary logistic regression analyses. Mean
age was 32 years, mean BMI was 29 kg m(-2) and mean WC was 89 cm. The sample
exhibited high PBF (44 %), and high rates of overweight (44%) and obesity (40%).
The threshold WC (>= 93 cm) had high sensitivity (80%), specificity (82%), Youden
Index value (0.62), and correct classification rate (82%). The area under the
receiver operating characteristic curve was 88 %. The WC >= 93 cm cut-off had
corresponding values for mean BMI (34 kg m-2) and PBF (47%). The optimal WC cut
off at 93 cm significantly identified central obesity for BMI >= 30 kg m-2 and
PBF for this sample.
PMID- 26425849
TI - Results of Automated Retinal Image Analysis for Detection of Diabetic Retinopathy
from the Nakuru Study, Kenya.
AB - OBJECTIVE: Digital retinal imaging is an established method of screening for
diabetic retinopathy (DR). It has been established that currently about 1% of the
world's blind or visually impaired is due to DR. However, the increasing
prevalence of diabetes mellitus and DR is creating an increased workload on those
with expertise in grading retinal images. Safe and reliable automated analysis of
retinal images may support screening services worldwide. This study aimed to
compare the Iowa Detection Program (IDP) ability to detect diabetic eye diseases
(DED) to human grading carried out at Moorfields Reading Centre on the population
of Nakuru Study from Kenya. PARTICIPANTS: Retinal images were taken from
participants of the Nakuru Eye Disease Study in Kenya in 2007/08 (n = 4,381
participants [NW6 Topcon Digital Retinal Camera]). METHODS: First, human grading
was performed for the presence or absence of DR, and for those with DR this was
sub-divided in to referable or non-referable DR. The automated IDP software was
deployed to identify those with DR and also to categorize the severity of DR.
MAIN OUTCOME MEASURES: The primary outcomes were sensitivity, specificity, and
positive and negative predictive value of IDP versus the human grader as
reference standard. RESULTS: Altogether 3,460 participants were included. 113 had
DED, giving a prevalence of 3.3% (95% CI, 2.7-3.9%). Sensitivity of the IDP to
detect DED as by the human grading was 91.0% (95% CI, 88.0-93.4%). The IDP
ability to detect DED gave an AUC of 0.878 (95% CI 0.850-0.905). It showed a
negative predictive value of 98%. The IDP missed no vision threatening
retinopathy in any patients and none of the false negative cases met criteria for
treatment. CONCLUSIONS: In this epidemiological sample, the IDP's grading was
comparable to that of human graders'. It therefore might be feasible to consider
inclusion into usual epidemiological grading.
PMID- 26425847
TI - Genome-Scale Mapping of Escherichia coli sigma54 Reveals Widespread, Conserved
Intragenic Binding.
AB - Bacterial RNA polymerases must associate with a sigma factor to bind promoter DNA
and initiate transcription. There are two families of sigma factor: the sigma70
family and the sigma54 family. Members of the sigma54 family are distinct in
their ability to bind promoter DNA sequences, in the context of RNA polymerase
holoenzyme, in a transcriptionally inactive state. Here, we map the genome-wide
association of Escherichia coli sigma54, the archetypal member of the sigma54
family. Thus, we vastly expand the list of known sigma54 binding sites to 135.
Moreover, we estimate that there are more than 250 sigma54 sites in total.
Strikingly, the majority of sigma54 binding sites are located inside genes. The
location and orientation of intragenic sigma54 binding sites is non-random, and
many intragenic sigma54 binding sites are conserved. We conclude that many
intragenic sigma54 binding sites are likely to be functional. Consistent with
this assertion, we identify three conserved, intragenic sigma54 promoters that
drive transcription of mRNAs with unusually long 5' UTRs.
PMID- 26425851
TI - Asia Pacific Stroke Conference 2015 Abstracts of the Annual Conference of the
Asia Pacific Stroke Organization (APSO) Kuala Lumpur, Malaysia, October 2-4,
2015: Abstracts.
PMID- 26425850
TI - Previous Exposure to Statin May Reduce the Risk of Subsequent Non-Hodgkin
Lymphoma: A Nationwide Population-Based Case-Control Study.
AB - BACKGROUND: The purpose of this study was to investigate the association between
previous exposure to statins and the risk of non-Hodgkin lymphoma (NHL). METHODS:
This nationwide population-based case-control study was conducted using the
National Health Insurance Research Database of Taiwan. The NHL group consisted of
the patients with a first-time diagnosis of NHL between 2005 and 2008. The cases
of the control group were pair-matched to the NHL group according to sex, year of
birth and date of NHL diagnosis (index date). The statin administration data from
both groups were retrospectively collected from the index date to January 1,
1996. The cumulative defined daily dose (cDDD) was estimated to evaluate the
statin exposure. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs)
were estimated using multivariate logistic regression. RESULTS: The study
population was composed of 1715 NHL patients and 16942 control subjects. The
analysis revealed that previous statin administration was associated with a
reduced risk of subsequent NHL with an adjusted OR of 0.52 (95% CI, 0.43-0.62).
Additionally, there was a dose-response relationship between statin
administration and the risk of NHL. The adjusted ORs were 0.63 (95% CI, 0.46
0.86), 0.58 (95% CI, 0.42-0.79), 0.51 (95% CI, 0.38-0.67), and 0.36 (95% CI, 0.24
0.53) for the subjects with statin administrations of fewer than 28, 28 to 90, 91
to 365, and more than 365 cDDDs, respectively, relative to the subjects without
any statin administration. CONCLUSIONS: The results of this study suggest that
previous statin administration is associated with a lower risk of subsequent NHL.
As statins are widely used medications, the magnitude of the risk reduction may
have a substantial influence on public health. Further studies to confirm our
findings are warranted.
PMID- 26425852
TI - Correction: Novel Compound Heterozygous Mutations in MYO7A Associated with Usher
Syndrome 1 in a Chinese Family.
PMID- 26425853
TI - Monte Carlo simulation of prompt gamma-ray emission in proton therapy using a
specific track length estimator.
AB - A Monte Carlo (MC) variance reduction technique is developed for prompt-gamma
emitters calculations in proton therapy. Prompt-gamma emitted through nuclear
fragmentation reactions and exiting the patient during proton therapy could play
an important role to help monitoring the treatment. However, the estimation of
the number and the energy of emitted prompt-gamma per primary proton with MC
simulations is a slow process. In order to estimate the local distribution of
prompt-gamma emission in a volume of interest for a given proton beam of the
treatment plan, a MC variance reduction technique based on a specific track
length estimator (TLE) has been developed. First an elemental database of prompt
gamma emission spectra is established in the clinical energy range of incident
protons for all elements in the composition of human tissues. This database of
the prompt-gamma spectra is built offline with high statistics. Regarding the
implementation of the prompt-gamma TLE MC tally, each proton deposits along its
track the expectation of the prompt-gamma spectra from the database according to
the proton kinetic energy and the local material composition. A detailed
statistical study shows that the relative efficiency mainly depends on the
geometrical distribution of the track length. Benchmarking of the proposed prompt
gamma TLE MC technique with respect to an analogous MC technique is carried out.
A large relative efficiency gain is reported, ca. 10(5).
PMID- 26425854
TI - Determinants of Default in P2P Lending.
AB - This paper studies P2P lending and the factors explaining loan default. This is
an important issue because in P2P lending individual investors bear the credit
risk, instead of financial institutions, which are experts in dealing with this
risk. P2P lenders suffer a severe problem of information asymmetry, because they
are at a disadvantage facing the borrower. For this reason, P2P lending sites
provide potential lenders with information about borrowers and their loan
purpose. They also assign a grade to each loan. The empirical study is based on
loans' data collected from Lending Club (N = 24,449) from 2008 to 2014 that are
first analyzed by using univariate means tests and survival analysis. Factors
explaining default are loan purpose, annual income, current housing situation,
credit history and indebtedness. Secondly, a logistic regression model is
developed to predict defaults. The grade assigned by the P2P lending site is the
most predictive factor of default, but the accuracy of the model is improved by
adding other information, especially the borrower's debt level.
PMID- 26425855
TI - A Review of Scientific Topics and Literature in Abdominal Radiology in Germany-
Part 2: Abdominal Parenchymal Organs.
AB - The working group for abdominal and gastrointestinal diagnosis is a group of the
German Radiological Society (DRG) focusing clinically and scientifically on the
diagnosis and treatment of the gastrointestinal tract as well as the parenchymal
abdominal organs. In this article we give an up-to-date literature review of
scientific radiological topics especially covered by German radiologists. The
working group experts cover the most recent relevant studies concerning liver
specific contrast media with an emphasis on a new classification system for liver
adenomas. Additionally studies regarding selective internal radiotherapy (SIRT)
are reviewed. For the pancreas the most important tumors are described followed
by an introduction to the most recently introduced functional imaging techniques.
The manuscript concludes with some remarks on recent studies and concerning
chronic pancreatitis as well as autoimmune pancreatitis. KEY POINTS: * Different
subtypes of liver adenomas with different therapeutic consequences can be
differentiated by MRI * Most recently published studies focus on liver imaging
with extracellular liver specific contrast media as well as diffusion weighted
imaging. They consider this new method having a high diagnostic potential. * For
pancreatic neoplasm diagnosis diffusion--as well as perfusion--imaging is
considered as a highly promising method.
PMID- 26425856
TI - [Cardiac metastasis of a recurrent urothelial carcinoma of the bladder].
PMID- 26425857
TI - Changes in Meningococcal Strains in the Era of a Serogroup C Vaccination
Campaign: Trends and Evolution in Belgium during the Period 1997-2012.
AB - BACKGROUND: Invasive meningococcal disease (IMD) is a major cause of bacterial
meningitides and septicaemia. This study shows the results of the laboratory
based surveillance of IMD in Belgium over the period 1997-2012. METHODS: The
results are based on microbiological and molecular laboratory surveillance of
2997 clinical isolates of N. meningitides received by the Belgian Meningococcal
Reference Centre (BMRC) over the period 1997-2012. RESULTS: Serogroup B has
always been a major cause of meningococcal disease in Belgium, with P3.4 as most
frequent serotype till 2008, while an increase in non-serotypable strains has
been observed in the last few years. Clonal complexes cc-41/44 and cc-269 are
most frequently observed in serogroup B strains. In the late nineties, the
incidence of serogroup C disease increased considerably and peaked in 2001,
mainly associated with phenotypes C:2a:P1.5,2, C:2a:P1.5 and C:2a:P1.2 (ST-11/ET
37 clonal complex). The introduction of the meningococcal C conjugate vaccine has
been followed by an 88% significant decrease in serogroup C disease from 2001 to
2004 nationally, yet sharper in Flanders (92%) compared to Wallonia (77%). Since
2008 a difference in incidence of serogroup C was observed in Flanders (0
0.1/100,000) versus Wallonia (0.1-0.3/100,000). CONCLUSION: This study showed the
change in epidemiology and strain population over a 16 years period spanning an
exhaustive vaccination campaign and highlights the influence of regional
vaccination policies with different cohorts sizes on short and long-term IMD
incidences.
PMID- 26425859
TI - Fetal Cardiac Axis in Fetuses with Conotruncal Anomalies.
AB - Purpose The purpose of this study was to assess the cardiac axis in fetuses with
conotruncal anomalies during four-chamber view scanning. Materials and Methods We
retrospectively evaluated the cardiac axis of 150 fetuses with conotruncal
anomalies within the second and third trimester between October 2008 and August
2014. The cardiac axis was obtained by the angle of two lines in a transverse
view of the fetal thorax at the level of the four-chamber view. The first line
divided the thorax into two equal halves starting from the spine posteriorly
ending at the sternum. The second line was placed through the interventricular
septum of the fetal heart. The angle was calculated using OsiriX software.
Results 23 had double outlet right ventricle (DORV), 17 had truncus arteriosus
communis (TAC), 36 had tetralogy of Fallot (TOF), and 74 had complete
transposition of the great arteries (d-TGA). In fetuses with DORV <= 24 + 6 weeks
of gestation (wks), the mean cardiac axis was 52.5 degrees (p = 0.005), at >= 25
+ 0 wks it was 51.1 degrees (p = 0.0003). In fetuses with TAC <= 24 + 6 wks, the
mean cardiac axis was 56.8 degrees (p = 0.01), at >= 25 + 0 wks it was 50.0
degrees (p = 0.05). In fetuses with TOF <= 24 + 6 wks, the mean cardiac axis was
67.5 degrees (p < 0.0001), at >= 25 + 0 wks it was 63.8 degrees (p < 0.0001).
In fetuses with d-TGA <= 24 + 6 wks, the mean cardiac axis was 45.6 degrees , at
>= 25 + 0 wks it was 45.4 degrees (not significant). Throughout gestation, the
cardiac axis did not show a difference in the two separate examinations.
Conclusion In fetuses with DORV, TAC and TOF, the cardiac axis is significantly
different from the normal axis, but in fetuses with TGA there is no significant
difference compared to the normal axis. Therefore, analysis of the heart axis
could be useful for screening for conotruncal anomalies.
PMID- 26425858
TI - Idiopathic Pulmonary Fibrosis: Gender-Age-Physiology Index Stage for Predicting
Future Lung Function Decline.
AB - BACKGROUND: Idiopathic pulmonary fibrosis is a progressive lung disease with
variable course. The Gender-Age-Physiology (GAP) Index and staging system uses
clinical variables to stage mortality risk. It is unknown whether clinical
staging predicts future decline in pulmonary function. We assessed whether the
GAP stage predicts future pulmonary function decline and whether interval
pulmonary function change predicts mortality after accounting for stage. METHODS:
Patients with idiopathic pulmonary fibrosis (N = 657) were identified
retrospectively at three tertiary referral centers, and baseline GAP stages were
assessed. Mixed models were used to describe average trajectories of FVC and
diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox
proportional hazards models were used to assess whether declines in pulmonary
function >= 10% in 6 months predict mortality after accounting for GAP stage.
RESULTS: Over a 2-year period, GAP stage was not associated with differences in
yearly lung function decline. After accounting for stage, a 10% decrease in FVC
or Dlco over 6 months independently predicted death or transplantation (FVC
hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P <= .03). Patients with GAP
stage 2 with declining pulmonary function experienced a survival profile similar
to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI,
49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). CONCLUSIONS: Baseline GAP stage
predicted death or lung transplantation but not the rate of future pulmonary
function decline. After accounting for GAP stage, a decline of >= 10% over 6
months independently predicted death or lung transplantation.
PMID- 26425860
TI - Image-based view-angle independent cardiorespiratory motion gating and coronary
sinus catheter tracking for x-ray-guided cardiac electrophysiology procedures.
AB - Determination of the cardiorespiratory phase of the heart has numerous
applications during cardiac imaging. In this article we propose a novel view
angle independent near-real time cardiorespiratory motion gating and coronary
sinus (CS) catheter tracking technique for x-ray fluoroscopy images that are used
to guide cardiac electrophysiology procedures. The method is based on learning CS
catheter motion using principal component analysis and then applying the derived
motion model to unseen images taken at arbitrary projections, using the epipolar
constraint. This method is also able to track the CS catheter throughout the x
ray images in any arbitrary subsequent view. We also demonstrate the clinical
application of our model on rotational angiography sequences. We validated our
technique in normal and very low dose phantom and clinical datasets. For the
normal dose clinical images we established average systole, end-expiration and
end-inspiration gating success rates of 100%, 85.7%, and 92.3%, respectively. For
very low dose applications, the technique was able to track the CS catheter with
median errors not exceeding 1 mm for all tracked electrodes. Average gating
success rates of 80.3%, 71.4%, and 69.2% were established for the application of
the technique on clinical datasets, even with a dose reduction of more than 10
times. In rotational sequences at normal dose, CS tracking median errors were
within 1.2 mm for all electrodes, and the gating success rate was 100%, for view
angles from RAO 90 degrees to LAO 90 degrees . This view-angle independent
technique can extract clinically useful cardiorespiratory motion information
using x-ray doses significantly lower than those currently used in clinical
practice.
PMID- 26425861
TI - Adolescents' Lived Experiences While Hospitalized After Surgery for Ulcerative
Colitis.
AB - Adolescents are in a transitional phase of life characterized by major physical,
emotional, and psychological challenges. Living with ulcerative colitis is
experienced as a reduction of their life quality. Initial treatment of ulcerative
colitis is medical, but surgery may be necessary when medical treatment ceases to
have an effect. No research-based studies of adolescents' experience of the
hospital period after surgery for ulcerative colitis exist. The objective of the
study was to identify and describe adolescents' lived experiences while
hospitalized after surgery for ulcerative colitis. This qualitative study was
based on interviews with eight adolescents. Analysis and interpretation were
based on a hermeneutic interpretation of meaning. Three themes were identified:
Body: Out of order; Seen and understood; and Where are all the others? The
adolescents experience a postoperative period characterized by physical and
mental impairment. Being mentally unprepared for such challenges, they shun
communication and interaction. The findings demonstrate the importance of
individualized nursing care on the basis of the adolescent's age, maturity, and
individual needs. Further study of adolescent patients' hospital stay, focusing
on the implications of being young and ill at the same time, is needed.
PMID- 26425862
TI - Nursing Assessment Tool for People With Liver Cirrhosis.
AB - The aim of this study was to describe the process of developing a nursing
assessment tool for hospitalized adult patients with liver cirrhosis. A
descriptive study was carried out in three stages. First, we conducted a
literature review to develop a data collection tool on the basis of the
Conceptual Model of Wanda Horta. Second, the data collection tool was assessed
through an expert panel. Third, we conducted the pilot testing in hospitalized
patients. Most of the comments offered by the panel members were accepted to
improve the tool. The final version was in the form of a questionnaire with open
closed questions. The panel members concluded that the tool was useful for
accurate nursing diagnosis. Horta's Conceptual Model assisted with the
development of this data collection tool to help nurses identify accurate nursing
diagnosis in hospitalized patients with liver cirrhosis. We hope that the tool
can be used by all nurses in clinical practice.
PMID- 26425864
TI - Predicting attitudes toward seeking professional psychological help among Alaska
Natives.
AB - This study sought to examine the role of current/previous treatment experience,
stigma (social and self), and cultural identification (Caucasian and Alaska
Native [AN]) in predicting attitudes toward psychological help seeking for ANs.
Results indicated that these variables together explained roughly 56% of variance
in attitudes. In particular, while self-stigma and identification with the
Caucasian culture predicted a unique amount of variance in help-seeking
attitudes, treatment use and identification with AN culture did not. The results
of this study indicate that efforts to address the experience of self-stigma may
prove most useful to improving help-seeking attitudes in ANs.
PMID- 26425863
TI - Post-traumatic stress disorder and HIV risk behaviors among rural American
Indian/Alaska Native women.
AB - We assessed the relationship between post-traumatic stress disorder (PTSD), binge
drinking, and HIV sexual risk behavior by examining number of unprotected sex
acts and number of sexual partners in the past 6 months among 129 sexually active
American Indian women. A total of 51 (39.5%) young women met PTSD criteria. Among
women who met the PTSD criteria, binge drinking was associated with a 35%
increased rate of unprotected sex (IRR 1.35, p < .05), and there was a stronger
association between increased binge drinking and risk of more sexual partners
(IRR 1.21, p < .001) than among women who did not meet PTSD criteria (IRR 1.08, p
< .01) with a difference of 13% (p < .05). HIV intervention and prevention
interventions in this population likely would benefit from the inclusion of
efforts to reduce binge drinking and increase treatment of PTSD symptoms.
PMID- 26425865
TI - Systematic review of interventions focusing on Indigenous adolescent mental
health and substance use.
AB - Mental health and substance use are pressing public health concerns among
Indigenous adolescent populations. This systematic review analyzed interventions
focusing on mental health and substance use that utilize the Positive Youth
Development (PYD) framework, incorporate culturally tailored programs, and are
geared toward Indigenous adolescents. In total, 474 articles were retrieved from
PSYCInfo and PubMed databases. Eight articles were eligible for analysis, with
six focusing on AI/AN populations in the U.S. Most programs reported positive or
expected outcomes. All the programs incorporated PYD variables, while all but one
were culturally grounded or included deep structure adaptations. Implications are
further discussed.
PMID- 26425866
TI - Iron Complexes of Square Planar Tetradentate Polypyridyl-Type Ligands as
Catalysts for Water Oxidation.
AB - The tetradentate ligand, 2-(pyrid-2'-yl)-8-(1",10"-phenanthrolin-2"-yl)-quinoline
(ppq) embodies a quaterpyridine backbone but with the quinoline C8 providing an
additional sp(2) center separating the two bipyridine-like subunits. Thus, the
four pyridine rings of ppq present a neutral, square planar host that is well
suited to first-row transition metals. When reacted with FeCl3, a MU-oxo-bridged
dimer is formed having a water bound to an axial metal site. A similar metal
binding environment is presented by a bis-phenanthroline amine (dpa) which forms
a 1:1 complex with FeCl3. Both structures are verified by X-ray analysis. While
the Fe(III)(dpa) complex shows two reversible one-electron oxidation waves, the
Fe(III)(ppq) complex shows a clear two-electron oxidation associated with the
process H2O-Fe(III)Fe(III) -> H2O-Fe(IV)Fe(IV) -> O?Fe(V)Fe(III). Subsequent
disproportionation to an Fe?O species is suggested. When the Fe(III)(ppq) complex
is exposed to a large excess of the sacrificial electron-acceptor ceric ammonium
nitrate at pH 1, copious amounts of oxygen are evolved immediately with a
turnover frequency (TOF) = 7920 h(-1). Under the same conditions the mononuclear
Fe(III)(dpa) complex also evolves oxygen with TOF = 842 h(-1).
PMID- 26425867
TI - Comparing the Maryland Comprehensive Cancer Control Plan With Federal Cancer
Prevention and Control Recommendations.
AB - INTRODUCTION: Since the introduction of the Affordable Care Act (ACA) in 2012, 11
million more Americans now have access to preventive services via health care
coverage. Several prevention-related recommendations issued by the US Preventive
Services Task Force (USPSTF), Centers for Disease Control and Prevention (CDC),
and Advisory Committee on Immunization Practices (ACIP) are covered under the
ACA. State cancer plans often provide prevention strategies, but whether these
strategies correspond to federal evidence-based recommendations is unclear. The
objective of this article is to assess whether federal evidence-based
recommendations, including those covered under the ACA, are included in the
Maryland Comprehensive Cancer Control Plan (MCCCP). METHODS: A total of 19
federal recommendations pertaining to cancer prevention and control were
identified. Inclusion of federal cancer-related recommendations by USPSTF, CDC,
and ACIP in the MCCCP's goals, objectives, and strategies was examined. RESULTS:
Nine of the federal recommendations were issued after the MCCCP's publication.
MCCCP recommendations corresponded completely with 4 federal recommendations and
corresponded only partially with 3. Reasons for partial correspondence included
specification of less restrictive at-risk populations or different intervention
implementers. Three federal recommendations were not mentioned in the MCCCP's
goals, objectives, and strategies. CONCLUSION: Many cancer-related federal
recommendations were released after the MCCCP's publication and therefore do not
appear in the most current version. We recommend that the results of this
analysis be considered in the update of the MCCCP. Our findings underscore the
need for a periodic scan for changes to federal recommendations and for adjusting
state policies and programs to correspond with federal recommendations, as
appropriate for Marylanders.
PMID- 26425868
TI - Using Photovoice to Understand Barriers to and Facilitators of Cardiovascular
Health Among African American Adults and Adolescents, North Carolina, 2011-2012.
AB - INTRODUCTION: Cardiovascular disease is the leading cause of death in the United
States, and mortality rates are higher among African Americans than among people
of other races/ethnicities. We aimed to understand how African American adults
and adolescents conceptualize cardiovascular health and perceive related barriers
and facilitators. METHODS: This qualitative study was conducted as formative
research for a larger study, Heart Healthy Lenoir, which aimed to reduce
cardiovascular disease disparities among African Americans in eastern North
Carolina, part of the widely-known "stroke belt" that runs through the
southeastern United States. Using photovoice, a community-based participatory
research method, we conducted eight 90-minute photovoice sessions with 6 adults
and 9 adolescents in Lenoir County, North Carolina. Topics for each discussion
were selected by participants and reflected themes related to cardiovascular
health promotion. All sessions were transcribed and coded using a data-driven,
inductive approach. RESULTS: Participants conceptualized cardiovascular health to
have mental, spiritual, and social health dimensions. Given these broad domains,
participants acknowledged many ecological barriers to cardiovascular health;
however, they also emphasized the importance of personal responsibility.
Facilitators for cardiovascular health included using social health (eg,
family/community relationships) and spiritual health dimensions (eg,
understanding one's body and purpose) to improve health behaviors. CONCLUSION:
The perspectives of African American adults and adolescents elicited through this
formative research provided a strong foundation for Heart Healthy Lenoir's
ongoing engagement of community members in Lenoir County and development and
implementation of its intervention to prevent cardiovascular disease.
PMID- 26425869
TI - Evaluating the Effects of Coping Style on Allostatic Load, by Sex: The Jackson
Heart Study, 2000-2004.
AB - The objective of this study was to examine the cross-sectional association
between coping styles and allostatic load among African American adults in the
Jackson Heart Study (2000-2004). Coping styles were assessed using the Coping
Strategies Inventory-Short Form; allostatic load was measured by using 9
biomarkers standardized into z-scores. Sex-stratified multivariable linear
regressions indicated that females who used disengagement coping styles had
significantly higher allostatic load scores (beta = 0.016; 95% CI, 0.001-0.032);
no such associations were found in males. Future longitudinal investigations
should examine why disengagement coping style is linked to increased allostatic
load to better inform effective interventions and reduce health disparities among
African American women.
PMID- 26425870
TI - New School Meal Regulations and Consumption of Flavored Milk in Ten US Elementary
Schools, 2010 and 2013.
AB - Milk is a source of shortfall nutrients in children's diets, but most children do
not consume recommended amounts. We measured consumption of milk by elementary
schoolchildren (grades 3-5) in a diverse sample of schools before and after
implementation of the US Department of Agriculture's updated meal regulations
requiring flavored milk to be fat-free. Flavored milk consumption did not change
from 2010 to 2013; 52.2% of students in 2010 and 49.7% in 2013 consumed 7 ounces
or more of an 8-ounce container. Updated regulations succeeded in lowering the
amount of fat, added sugars, and calories in school milk but did not change
overall milk consumption, thus improving children's diet quality.
PMID- 26425872
TI - Detectability of hepatic tumors during 3D post-processed ultrafast cone-beam
computed tomography.
AB - To evaluate hepatic tumor detection using ultrafast cone-beam computed tomography
(UCBCT) cross-sectional and 3D post-processed image datasets. 657 patients were
examined using UCBCT during hepatic transarterial chemoembolization (TACE), and
data were collected retrospectively from January 2012 to September 2014. Tumor
detectability, diagnostic ability, detection accuracy and sensitivity were
examined for different hepatic tumors using UCBCT cross-sectional, perfusion
blood volume (PBV) and UCBCT-MRI (magnetic resonance imaging) fused image
datasets. Appropriate statistical tests were used to compare collected sample
data. Fused image data showed the significantly higher (all P < 0.05)
diagnostic ability for hepatic tumors compared to UCBCT or PBV image data. The
detectability of small hepatic tumors (<5 mm) was significantly reduced (all P <
0.05) using UCBCT cross-sectional images compared to MRI or fused image data;
however, PBV improved tumor detectability using a color display. Fused image data
produced 100% tumor sensitivity due to the simultaneous availability of MRI and
UCBCT information during tumor diagnosis. Fused image data produced excellent
hepatic tumor sensitivity, detectability and diagnostic ability compared to other
datasets assessed. Fused image data is extremely reliable and useful compared to
UCBCT cross-sectional or PBV image datasets to depict hepatic tumors during TACE.
Partial anatomical visualization on cross-sectional images was compensated by
fused image data during tumor diagnosis.
PMID- 26425871
TI - Strategies to Support Tobacco Cessation and Tobacco-Free Environments in Mental
Health and Substance Abuse Facilities.
AB - We identified and described strategies for promoting smoking cessation and smoke
free environments that were implemented in Oregon and Utah in treatment centers
for mental illness and substance abuse. We reviewed final evaluation reports
submitted by state tobacco control programs (TCPs) to the Centers for Disease
Control and Prevention and transcripts from a call study evaluation. The TCPs
described factors that assisted in implementing strategies: being ready for
opportunity, having a sound infrastructure, and having a branded initiative.
These strategies could be used by other programs serving high-need populations
for whom evidence-based interventions are still being developed.
PMID- 26425873
TI - Nephrologists' Perspectives on Recipient Eligibility and Access to Living Kidney
Donor Transplantation.
AB - BACKGROUND: Wide variations in access to living kidney donation are apparent
across transplant centers. Such disparities may be in part explained by
nephrologists' beliefs and decisions about recipient eligibility. This study aims
to describe nephrologists' attitudes towards recipient eligibility and access to
living kidney donor transplantation. METHODS: Face-to-face semistructured
interviews were conducted from June to October 2013 with 41 nephrologists from
Australia and New Zealand. Transcripts were analyzed thematically. RESULTS: We
identified five major themes: championing optimal recipient outcomes (maximizing
recipient survival, increasing opportunity, accepting justified risks, needing
control and certainty of outcomes, safeguarding psychological wellbeing),
justifying donor sacrifice (confidence in reasonable utility, sparing the donor,
ensuring reciprocal donor benefit), advocating for patients (being proactive and
encouraging, addressing ambivalence, depending on supportive infrastructure,
avoiding selective recommendations), maintaining professional boundaries
(minimizing conflict of interest, respecting shared decision-making, emphasizing
patient accountability, restricted decisional power, protecting unit interests),
and entrenched inequities (exclusivity of living donors, inherently advantaging
self-advocates, navigating language barriers, increasing center transparency,
inevitable geographical disadvantage, understanding cultural barriers).
CONCLUSIONS: Nephrologists' decisions about recipient suitability for living
donor transplantation aimed to achieve optimal recipient outcomes, but were
constrained by competing priorities to ensure reasonable utility derived from the
donor kidney and protect the integrity of the transplant program. Comprehensive
guidelines that provide explicit recommendations for complex medical and
psychosocial risk factors might promote more equitable and transparent decision
making. Psychosocial support and culturally sensitive educational resources are
needed to help nephrologists advocate for disadvantaged patients and address
disparities in access to living kidney donor transplantation.
PMID- 26425874
TI - Ventilatory Management During Normothermic Ex Vivo Lung Perfusion: Effects on
Clinical Outcomes.
AB - BACKGROUND: During ex vivo lung perfusion (EVLP), fixed ventilator settings and
monitoring of compliance are used to prevent ventilator-induced lung injury
(VILI). Analysis of the airway pressure-time curve (stress index) has been
proposed to assess the presence of VILI. We tested whether currently proposed
ventilator settings expose lungs to VILI during EVLP and whether the stress index
could identify VILI better than compliance. METHODS: Flow, volume, and airway
opening pressure were collected continuously during EVLP. Durations of mechanical
ventilation, intensive care unit (ICU) and hospital lengths of stay were recorded
in lung recipients. RESULTS: Fourteen lungs underwent EVLP and were transplanted.
In 5 lungs, 95 +/- 2% of the stress index values were within the 0.95 to 1.05
range (protected); in the remaining nine lungs, 69 +/- 1% of the values were
greater than 1.05 and 15 +/- 3% were less than 0.95 (nonprotected). There was a
significant (P < 0.05) increase in cytokine concentrations after 4 hours of EVLP
in the nonprotected lungs. Durations of mechanical ventilation, ICU, and hospital
lengths of stay were shorter in recipients of protected than that of nonprotected
lungs (P < 0.05). There was no correlation between compliance during EVLP and
duration of mechanical ventilation or ICU and hospital lengths of stay in
recipients, but the stress index during EVLP was significantly correlated with
the duration of mechanical ventilation and with ICU and hospital lengths of stay
(P < 0.05). CONCLUSIONS: This small, preliminary study shows that ventilator
settings currently proposed for EVLP may expose lungs to VILI. Use of the stress
index to personalize ventilator settings needs to be tested in further clinical
studies.
PMID- 26425875
TI - Quantifying the Race Stratified Impact of Socioeconomics on Graft Outcomes in
Kidney Transplant Recipients.
AB - BACKGROUND: Socioeconomic status (SES) is a significant determinant of health
outcomes and may be an important component of the causal chain surrounding racial
disparities in kidney transplantation. The social adaptability index (SAI) is a
validated and quantifiable measure of SES, with a lack of studies analyzing this
measure longitudinally or between races. METHODS: Longitudinal cohort study in
adult kidney transplantation transplanted at a single-center between 2005 and
2012. The SAI score includes 5 domains (employment, education, marital status,
substance abuse and income), each with a minimum of 0 and maximum of 3 for an
aggregate of 0 to 15 (higher score -> better SES). RESULTS: One thousand one
hundred seventy-one patients were included; 624 (53%) were African American (AA)
and 547 were non-AA. African Americans had significantly lower mean baseline SAI
scores (AAs 6.5 vs non-AAs 7.8; P < 0.001). Cox regression analysis demonstrated
that there was no association between baseline SAI and acute rejection in non-AAs
(hazard ratio [HR], 0.92; 95% confidence interval [95% CI], 0.81-1.05), whereas
it was a significant predictor of acute rejection in AAs (HR, 0.89; 95% CI, 0.80
0.99). Similarly, a 2-stage approach to joint modelling of time to graft loss and
longitudinal SAI did not predict graft loss in non-AAs (HR, 1.01; 95% CI, 0.28
3.62), whereas it was a significant predictor of graft loss in AAs (HR, 0.23; 95%
CI, 0.06-0.93). CONCLUSIONS: After controlling for confounders, SAI scores were
associated with a lower risk of acute rejection and graft loss in AA kidney
transplant recipients, whereas neither baseline nor follow-up SAI predicted
outcomes in non-AA kidney transplant recipients.
PMID- 26425876
TI - Preconditioning Therapy in ABO-Incompatible Living Kidney Transplantation: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: ABO-incompatible (ABOi) kidney transplantation is now an established
form of renal replacement therapy, but the efficacy and safety of the different
types of preconditioning therapies are unclear. We aimed to synthesize the
totality of the published evidence about the effects of any form of
preconditioning therapies in living donor ABOi kidney transplantation on graft
and patient outcomes. METHODS: We searched MEDLINE, Embase, and Clinicaltrial.gov
databases (inception through June 2015) to identify all studies that described
the outcomes of adult living donor ABOi kidney transplantations using any form of
preconditioning therapies. Two independent reviewers identified studies,
extracted data, and assessed the risk of bias. Data were summarized using the
random effects model, and heterogeneity was explored using subgroup analyses. We
assessed confidence in the evidence using the Grading of Recommendations
Assessment, Development, and Evaluation framework. RESULTS: Eighty-three studies
(54 case reports and case series, 25 cohort, 2 case-control, and 2 registry
studies) involving 4810 ABOi transplant recipients were identified. Overall,
confidence in the available evidence was low. During a mean follow-up time of 28
(standard deviation [SD], 26.6) months, the overall graft survival for recipients
who received immunoadsorption or apheresis was 94.1% (95% confidence interval
[95%CI], 88.2%-97.1%) and 88.0% (95% CI, 82.6%-91.8%), respectively. For those
who received rituximab or underwent splenectomy, the overall graft survival was
94.5% (95% CI, 91.6%-96.5%) and 79.7% (95% CI, 72.9%-85.1%), respectively. Data
on other longer-term outcomes, including malignancy, were sparse. CONCLUSIONS:
Rituximab or immunoadsorption appeared to be promising preconditioning strategies
before ABOi kidney transplantation. However, the overall quality of evidence and
the confidence in the observed treatment effects are low. The increased use of
ABOi kidney transplantation needs to be matched with randomized trials of
different types, dosing, and frequency of preconditioning therapies so that this
scarce resource can be used most effectively and efficiently.
PMID- 26425877
TI - Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor
2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and
Predictor of Delayed and Slow Graft Function After Kidney Transplantation.
AB - BACKGROUND: Delayed graft function (DGF) and slow graft function (SGF) are
ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long
term graft survival after kidney transplantation. Regulatory T (Treg) cells are
protective in murine AKI, and their suppressive function predictive of AKI in
kidney transplantation. The conventional Treg cell function coculture assay is
however time-consuming and labor intensive. We sought a simpler alternative to
measure Treg cell function and predict AKI. METHODS: In this prospective
observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/
and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were
measured by flow cytometry in 76 deceased donor kidney transplant recipients
(DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset
of 37 recipients, pretransplant circulating Treg cell-suppressive function was
also quantified by measuring the suppression of autologous effector T-cell
proliferation by Treg cell in coculture. RESULTS: The TNFR2+ expression on
CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P
< 0.01). In receiver operating characteristic curves, percentage and absolute
number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF)
with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF +
SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P <
0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in
multivariate logistic regression accounting for cold ischemic time, donor age,
previous transplant, and pretransplant dialysis modality. CONCLUSIONS:
Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially
a simpler alternative to Treg cell function as a pretransplant recipient immune
marker for AKI (DGF + SGF), independent from donor and organ procurement
characteristics.
PMID- 26425878
TI - Transformation between Inverse Bicontinuous Cubic Phases of a Lipid from Diamond
to Gyroid.
AB - The transformation between inverse bicontinuous cubic phases of a lipid from
diamond (QII(D)) to gyroid (QII(G)) in the single crystal region of monoolein was
studied. X-ray diffraction data indicate that the single orientation of the
QII(D) phase was converted into an almost single orientation of the QII(G) phase.
The [111] and [110] directions of a single crystal of the QII(D) phase
corresponded to the [202] and [040] directions of the QII(G) phase, respectively.
This orientation relationship indicated that one direction in the four-branched
water channels of the QII(D) phase was preserved in the three-branched water
channels of the QII(G) phase. Using this relationship, a transformation model was
constructed in which one direction of the water channels was preserved while
another direction appeared.
PMID- 26425879
TI - Cardiac Troponin Measurement in the Critically Ill: Potential for Guiding
Clinical Management.
AB - BACKGROUND: Elevated cardiac troponin (cTn) in the absence of acute coronary
syndromes (ACS) is associated with increased mortality in critically ill
patients. There are no evidence-based interventions that reduce mortality in this
group. OBJECTIVES: We performed a retrospective investigation of the Veterans
Administration Inpatient Evaluation Center database to determine whether drugs
used in ACS (beta-blockers, aspirin, and statins) are associated with reduced
mortality in critically ill patients. METHODS: Thirty-day mortality was
determined for non-ACS patients admitted to any Veterans Administration Intensive
Care Unit between October 1, 2007, and September 30, 2008, adjusted for severity
of illness. Troponin assay values were normalized across institutions. RESULTS:
Multivariate analyses for 30-day mortality showed an odds ratio (OR) of 1.82 for
patients with high cTn (P < 0.0001, cTn > 10% coefficient of variation) and 1.18
for intermediate cTn (P = 0.0021, cTn between lowest limit detectable and 10%
coefficient of variation) compared with patients with no elevation, adjusting for
severity of illness (n = 19,979). Logistic regression models showed that patients
with no or intermediate elevations of cTn taking statins within 24 hours of cTn
measurement had a lower mortality than patients not taking statins (OR, 0.66; 95%
confidence interval [95% CI], 0.53-0.82; P = 0.0003), whereas patients with high
cTn had a lower mortality if they were taking beta-blockers or aspirin within 24
hours of cTn measurement compared to patients not taking beta-blockers or aspirin
(beta-blockers: OR, 0.80; 95% CI, 0.68-0.94; P = 0.0077; aspirin: OR, 0.81;95%
CI, 0.69-0.96; P = 0.0134). CONCLUSIONS: This retrospective study confirms an
association between elevated troponin and outcomes in critically ill patients
without ACS and identifies statins, beta-blockers, and aspirin as potential
outcome modifiers in a cTn-dependent manner.
PMID- 26425882
TI - Correction to Spectroscopy and Structure of the Simplest Actinide Bonds.
PMID- 26425881
TI - Are You Missing an Entropion? The Test of Induced Entropion 2.
AB - PURPOSE: Entropion is the inward turning of the eyelid. The most common type of
entropion is involutional, a combination of eyelid laxity, lower eyelid retractor
weakness, and orbicularis oculi override. Unfortunately, the condition can be
intermittent and remain undiagnosed, leading to ocular surface damage. In
suspected cases, clinicians can use provocation techniques to elicit the
condition. These include the forced closure of the eyelids, the tetracaine
provocation test, and the test of induced entropion (TIE). The authors present an
alternative diagnostic test: the TIE-2. METHODS: The TIE-2 test is performed by
asking the patient to look down while the examiner holds the upper eyelid open
and high to prevent downward movement. The patient is then asked to close their
eyelids as tightly as possible. An entropion will then be induced. To illustrate
the technique, the authors present 2 patients seen in the oculoplastics clinic
with symptoms and signs suggestive of intermittent entropion, in whom
conventional provocation tests were unsuccessful. RESULTS: In both cases,
conventional methods did not provoke an entropion. However, the TIE-2 test
successfully induced an entropion, leading to the correct diagnosis and
appropriate management. CONCLUSION: When there is suspicion of intermittent
entropion that is not revealed with existing provocation tests, the TIE-2 is a
simple and useful diagnostic tool.
PMID- 26425883
TI - Intranasal Human Growth Hormone (hGH) Induces IGF-1 Levels Comparable With
Subcutaneous Injection With Lower Systemic Exposure to hGH in Healthy Volunteers.
AB - CONTEXT: The development of an improved, efficacious human GH (hGH) product
administered by a noninjectable route of delivery such as the nasal route is
highly desirable. We have developed a novel nasal hGH product (CP024) that showed
excellent nasal absorption in animal models; however, the translation of these
results into the clinical setting is essential because past attempts to develop
such formulations by other groups have been unable to induce IGF-1 in man.
OBJECTIVE: The objective of the study was to assess the pharmacokinetics,
pharmacodynamics, and tolerability of CP024 compared with a sc hGH injection.
DESIGN: This was a single-center, nonrandomized placebo-controlled, open-label,
five-way crossover study in eight healthy volunteers. SETTING: The study was
carried out at a contract research organization, Quotient Bioresearch.
VOLUNTEERS: Eight healthy male volunteers, given an iv infusion of octreotide to
suppress the endogenous GH secretion during the study period, participated in the
study. No volunteers were withdrawn due to side effects. MAIN OUTCOME MEASURES:
Measurement of hGH and IGF-1 levels and tolerability of the drug product was
performed. RESULTS: No serious adverse events were reported and no subjects
withdrawn from study due to the treatment. After the nasal administration of
CP024, 3-fold higher hGH blood levels were obtained as compared with hGH nasal
control. The relative bioavailability was about 3%. CP024 (given twice daily)
induced a significant increase in IGF-1 levels up to 19 hours after
administration, with no significant difference to those obtained after the sc
injection of hGH. CONCLUSIONS: The study indicates that CP024 is a promising
candidate for an efficacious nasal product for the treatment of GH deficiency due
to induction of IGF-1 similar to that after a sc injection, despite the lower
plasma hGH concentration obtained. A dose-response study is needed to evaluate
the optimal nasal dose.
PMID- 26425885
TI - Chenodeoxycholic Acid as a Potential Prognostic Marker for Roux-en-Y Gastric
Bypass in Chinese Obese Patients.
AB - CONTEXT: Bile acids (BAs) have been suggested as key mediators of the
improvements in glucose metabolism after Roux-en-Y gastric bypass (RYGB).
OBJECTIVE: The objective of the study was to test whether the individual or a
group of BAs have potential value to predict diabetes remission after RYGB.
DESIGN AND PATIENTS: A retrospective cohort of 38 Chinese obese patients with
type 2 diabetes mellitus (T2DM) who had undergone RYGB and a cross-sectional
cohort of 327 subjects from the Shanghai Obesity Study were involved in the
study. MAIN OUTCOME AND MEASURES: We applied a targeted metabolomics approach to
quantitatively measure 26 serum BAs. The relative proportion of each BA in total
BAs was calculated. RESULTS: In the metabolic surgery study, RYGB was effective
in the reduction of body weight in both remission and nonremission groups. The
reductions of body mass index (BMI) in both groups were 7.34 +/- 2.10 kg/m(2) and
6.31 +/- 2.38 kg/m(2), respectively (P = .14). Patients in the remission group
had a shorter duration of diabetes, lower glycated hemoglobin, and higher C
peptide and chenodeoxycholic acid (CDCA) proportion at baseline compared with the
nonremission group. Multiple logistic regression indicated that a higher level of
CDCA relative to total BA (CDCA%) and shorter duration of diabetes at baseline
were associated with a greater chance of diabetes remission. The odd ratios were
0.19 (95% confidence interval 0.05-0.74) and 1.77 (95% confidence interval 1.13
2.76), respectively, after adjustment for age, gender, and BMI. In the cross
sectional study, CDCA% was significantly higher in obese individuals with T2DM
than the normal glucose tolerance group. Correlation analysis showed CDCA% was
positively correlated with BMI, glycated hemoglobin, triglycerides, and low
density lipoprotein cholesterol and negatively correlated with high-density
lipoprotein cholesterol and diabetes duration. CONCLUSION: Increased CDCA, a
major primary BA, was correlated with a shorter duration of T2DM, which was
associated with a higher possibility of remission after surgery. CDCA% might act
as a potential prognostic marker of RYGB.
PMID- 26425884
TI - Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines
in Obese Women.
AB - CONTEXT: Obesity is associated with a pro-inflammatory state and relative
hypogonadotropic hypogonadism. Estrogen (E2) is a potential link between these
phenomena because it exhibits negative feedback on gonadotropin secretion and
also inhibits production of pro-inflammatory cytokines. OBJECTIVE: We sought to
examine the effect of estrogen priming on the hypothalamic-pituitary-ovarian axis
in obesity. DESIGN, SETTING, AND PARTICIPANTS: This was an interventional study
at an academic center of 11 obese and 10 normal-weight (NW) women. INTERVENTION:
A frequent blood-sampling study and one month of daily urinary collection were
performed before and after administration of transdermal estradiol 0.1 mg/d for
one entire menstrual cycle. MAIN OUTCOME MEASURES: Serum LH and FSH before and
after GnRH stimulation, and urinary estrogen and progesterone metabolites were
measured. RESULTS: E2 increased LH pulse amplitude and FSH response to GnRH (P =
.048, and P < .03, respectively) in obese but not NW women. After E2 priming,
ovulatory obese but not NW women had a 25% increase in luteal progesterone (P =
.01). Obese women had significantly higher baseline IL-6, IL-10, TGF-beta, and IL
12 compared with NW (all P < .05); these levels were reduced after E2 (-6% for IL
1beta, -21% for IL-8, -5% for TGF-beta, -5% for IL-12; all P < .05) in obese but
not in NW women. CONCLUSIONS: E2 priming seems to improve hypothalamic-pituitary
ovarian axis function and systemic inflammation in ovulatory, obese women.
Reducing chronic inflammation at the pituitary level may decrease the burden of
obesity on fertility.
PMID- 26425891
TI - Author's reply to Performance of interferon-gamma release assay for tuberculosis
screening in inflammatory bowel disease patients: disease activity as an
influencing factor.
PMID- 26425892
TI - Pyridine-Hydrazones as N,N'-Ligands in Asymmetric Catalysis: Pd(II)-Catalyzed
Addition of Boronic Acids to Cyclic Sulfonylketimines.
AB - The design, synthesis, and coordination features of a novel class of chiral
pyridine-hydrazone ligands are described. As a first application, L/Pd(TFA)2
complexes served as catalysts in the 1,2-addition of arylboronic acids to
saccharin-derived cyclic ketimines, affording products in high yields and
enantioselectivities. The method was also applied to more challenging 3,4
disubstituted 1,2,5-thiadiazole 1,1-dioxides, affording again high yields and
enantioselectivities along with high regioselectivities for unsymmetrically
substituted derivatives.
PMID- 26425886
TI - Timing of Estradiol Treatment After Menopause May Determine Benefit or Harm to
Insulin Action.
AB - CONTEXT: Type 2 diabetes (T2D) is reduced in postmenopausal women randomized to
estrogen-based hormone therapy (HT) compared with placebo. Insulin sensitivity is
a key determinant of T2D risk and overall cardiometabolic health, and studies
indicate that estradiol (E2) directly impacts insulin action. OBJECTIVE: We
hypothesized that the timing of E2 administration after menopause is an important
determinant of its effect on insulin action. DESIGN: We performed a randomized,
crossover, placebo-controlled study. PARTICIPANTS: Study participants were early
postmenopausal (EPM; <= 6 years of final menses; n = 22) and late postmenopausal
(LPM; >= 10 years since last menses; n = 24) women naive to HT. INTERVENTION:
Study interventions included short-term (1 week) transdermal E2 and placebo. MAIN
OUTCOMES AND MEASURES: The study's main outcome was insulin-mediated glucose
disposal (glucose disposal rate [GDR]) via hyperinsulinemic-euglycemic clamp.
RESULTS: Compared to EPM women, LPM women were older (mean +/- SD; 63 +/- 3 vs 56
+/- 4 years, P < .05) and more years past menopause (12 +/- 2 vs 3 +/- 2 years, P
< .05). Body mass index (24 +/- 3 vs 25 +/- 7 kg/m(2)) and fat mass (25 +/- 7 vs
23 +/- 6 kg) did not differ between groups, but fat-free mass (FFM) was lower in
LPM women compared to EPM women (40 +/- 4 vs 43 +/- 5 kg, P < .05). Baseline GDR
did not differ between groups (11.7 +/- 2.8 vs 11.5 +/- 2.9 mg/kg FFM/min). In
support of our hypothesis, 1 week of E2 decreased GDR in LPM women compared to an
increase in EPM women (+0.44 +/- 1.7 vs - 0.76 +/- 2.1 mg/kg FFM/min, P < .05).
CONCLUSIONS: There was not an apparent decline in GDR with age or time since
menopause per se. However, E2 action on GDR was dependent on time since
menopause, such that there was an apparent benefit early (<= 6 years) compared to
harm later (>= 10 years) in menopause. E2-mediated effects on insulin action may
be one mechanism by which HT reduces the incidence of T2D in early postmenopausal
women.
PMID- 26425893
TI - An Update on Hantaviruses.
PMID- 26425894
TI - Molecular Characterization of Murine Monoclonal Antibody Variable Regions
Specific for Hepatitis B Surface Antigen.
AB - BACKGROUND: Hepatitis B virus (HBV) surface antigen (HBsAg) induces a vigorous
neutralizing antibody response, which causes effective protection against HBV
infection. Little is known about the profile of variable region genes of
immunoglobuline heavy (VH) and light (VL) chains rearranged in anti-HBs
antibodies, and also the possible association of this profile with specificity
pattern of these antibodies to mutant forms of HBsAg. AIMS: The present study
determined the nucleotide sequence of VH and VL genes of mouse monoclonal
antibodies (MAbs) generated against HBsAg. METHODS: Hybridoma clones secreting
anti-HBsAg MAbs were developed from hyperimmunized Balb/c mice. VH and VL gene
sequences of all MAbs were determined by amplifying the genes using a panel of VH
and VL family specific primers by reverse transcription polymerase chain
reaction. The reactivity pattern of anti-HBs MAbs with different mutant forms of
HBsAg was evaluated by enzyme-linked immunosorbent assay, and then the profile of
antigen specificity and its association to VH/VL family expression was analyzed.
RESULTS: Twenty-three murine hybridomas producing anti-HBs MAbs were generated.
Nucleotide sequence analysis revealed that heavy chains of these MAbs were
encoded by IGHV genes from the HV1 (52%), HV6 (22%), HV5 (17%), and HV3 (9%)
families in combination with IGHJ2 (57%), HJ1 (26%), and HJ4 (17%). Besides, 56%
of MAbs used IGHD1 genes in their VDJ rearrangements. Concerning the IGKV gene,
26% and 22% of clones used KV4 and KV10 gene families, while the rest of the
clones used KV8, KV6, KV1, KV12, and KV14 gene families. Besides, the IGKJ2 gene
was the most represented KJ gene (43%). No association was found between the
specificity pattern of MAbs to mutant forms of HBsAg with their preferential V,
D, and J genes usage for most of MAbs. CONCLUSION: The data suggest that heavy
chains of anti-HBs MAbs preferentially use genes derived from the IGHV1, IGHV6,
IGHJ2, and IGHD1 families. In contrast to heavy chains, which predominantly use
four families of IGHV genes, light chains use more diverse IGKV gene families.
PMID- 26425896
TI - The MCART Consortium Animal Model Series: MCART Animal Model Refinement and MCM
Development: Defining organ dose, organ-specific tissue imaging, model validation
and the natural history between the acute radiation syndrome (ARS) and the
delayed effects of acute radiation exposure (DEARE).
PMID- 26425897
TI - The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A
Systematic Review of the Lethal Dose Response Relationship.
AB - Well characterized animal models that mimic the human response to potentially
lethal doses of radiation are required to assess the efficacy of medical
countermeasures under the criteria of the U.S. Food and Drug Administration
"animal rule." Development of a model requires the determination of the radiation
dose response relationship and time course of mortality and morbidity across the
hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is
a relevant animal model that may be used to determine the efficacy of medical
countermeasures to mitigate major signs of morbidity and mortality at selected
lethal doses of total body irradiation. A systematic review of relevant studies
that determined the dose response relationship for the hematopoietic acute
radiation syndrome in the rhesus macaque relative to radiation quality, dose
rate, and exposure uniformity has never been performed. The selection of data
cohorts was made from the following sources: Ovid Medline (1957-present), PubMed
(1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S.
HHS REPORT (2002 to present). The following terms were used: Rhesus, total body
irradiation, total body x irradiation, TBI, irradiation, gamma radiation,
hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate,
NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear
radiation. The reference lists of all studies, published and unpublished, were
reviewed for additional studies. The total number of hits across all search sites
was 3,001. There were a number of referenced, unpublished, non-peer reviewed
government reports that were unavailable for review. Fifteen studies, 11 primary
(n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates
(NHP), rhesus Macaca mulatta] were evaluated to provide an informative and
consistent review. The dose response relationships (DRRs) were determined for
uniform or non-uniform total body irradiation (TBI) with 250 kVp or 2 MeV x
radiation, Co gamma radiation and reactor- and nuclear weapon-derived mixed
gamma: neutron-radiation, delivered at various dose rates from a total body,
bilateral, rotational, or unilateral exposure aspect. The DRRs established by a
probit analysis vs. linear dose relationship were characterized by two main
parameters or dependent variables: a slope and LD50/30. Respective LD50/30 values
for studies that used 250 kVp x radiation (five primary studies combined, n =
338), 2 MeV x radiation, Co gamma radiation, and steady-state reactor-derived
mixed gamma:neutron radiation for total body uniform exposures were 521 rad [498,
542], 671 rad [632, 715], 644 rad [613, 678], and 385 rad [357, 413]. The
respective slopes were steep and ranged from 0.738 to 1.316. The DRR, LD50/30
values and slopes were also determined for total body, non-uniform, unilateral,
pulse-rate exposures of mixed gamma:neutron radiation derived at reactor and
nuclear weapon detonations. The LD50/30 values were, respectively, 395 rad [337,
432] and 412 rad [359, 460]. Secondary data sets of limited studies that did not
describe a DRR were used to support the mid-to-high lethal dose range for the H
ARS and the threshold dose range for the concurrent acute GI ARS. The available
evidence provided a reliable and extensive database that characterized the DRR
for the H-ARS in young rhesus macaques exposed to 250 kVp uniform total body x
radiation without the benefit of medical management. A less substantial but
consistent database demonstrated the DRR for total body exposure of differing
radiation quality, dose rate and non-uniform exposure. The DRR for the H-ARS is
characterized by steep slopes and relative LD50/30 values that reflect the
radiation quality, exposure aspect, and dose rate over a range in time from 1954
2012.
PMID- 26425898
TI - Mean Organ Doses Resulting From Non-Human Primate Whole Thorax Lung Irradiation
Prescribed to Mid-Line Tissue.
AB - Multi-organ dose evaluations and the effects of heterogeneous tissue dose
calculations have been retrospectively evaluated following irradiation to the
whole thorax and lung in non-human primates (NHP). A clinical-based approach was
established to evaluate actual doses received in the heart and lungs during whole
thorax lung irradiation. Anatomical structure and organ densities have been
introduced in the calculations to show the effects of dose distribution through
heterogeneous tissue. Mean organ doses received by non-human primates undergoing
whole thorax lung irradiations were calculated using a treatment planning system
that is routinely used in clinical radiation oncology. The doses received by non
human primates irradiated following conventional dose calculations have been
retrospectively reconstructed using computerized tomography-based, heterogeneity
corrected dose calculations. The use of dose volume descriptors for irradiation
to organs at risk and tissue exposed to radiation is introduced. Mean and partial
volume doses to lung and heart are presented and contrasted. The importance of
exact dose definitions is highlighted, and the relevance of precise dosimetry to
establish organ-specific dose response relationships in NHP models of acute and
delayed effects of acute radiation exposure is emphasized.
PMID- 26425899
TI - Increased Expression of Connective Tissue Growth Factor (CTGF) in Multiple Organs
After Exposure of Non-Human Primates (NHP) to Lethal Doses of Radiation.
AB - Exposure to sufficiently high doses of ionizing radiation is known to cause
fibrosis in many different organs and tissues. Connective tissue growth factor
(CTGF/CCN2), a member of the CCN family of matricellular proteins, plays an
important role in the development of fibrosis in multiple organs. The aim of the
present study was to quantify the gene and protein expression of CTGF in a
variety of organs from non-human primates (NHP) that were previously exposed to
potentially lethal doses of radiation. Tissues from non-irradiated NHP and NHP
exposed to whole thoracic lung irradiation (WTLI) or partial-body irradiation
with 5% bone marrow sparing (PBI/BM5) were examined by real-time quantitative
reverse transcription PCR, western blot, and immunohistochemistry. Expression of
CTGF was elevated in the lung tissues of NHP exposed to WTLI relative to the lung
tissues of the non-irradiated NHP. Increased expression of CTGF was also observed
in multiple organs from NHP exposed to PBI/BM5 compared to non-irradiated NHP;
these included the lung, kidney, spleen, thymus, and liver. These irradiated
organs also exhibited histological evidence of increased collagen deposition
compared to the control tissues. There was significant correlation of CTGF
expression with collagen deposition in the lung and spleen of NHP exposed to
PBI/BM5. Significant correlations were observed between spleen and multiple
organs on CTGF expression and collagen deposition, respectively, suggesting
possible crosstalk between spleen and other organs. These data suggest that CTGF
levels are increased in multiple organs after radiation exposure and that
inflammatory cell infiltration may contribute to the elevated levels of CTGF in
multiple organs.
PMID- 26425900
TI - The H-ARS Dose Response Relationship (DRR): Validation and Variables.
AB - Manipulations of lethally-irradiated animals, such as for administration of
pharmaceuticals, blood sampling, or other laboratory procedures, have the
potential to induce stress effects that may negatively affect morbidity and
mortality. To investigate this in a murine model of the hematopoietic acute
radiation syndrome, 20 individual survival efficacy studies were grouped based on
the severity of the administration (Admn) schedules of their medical
countermeasure (MCM) into Admn 1 (no injections), Admn 2 (1-3 injections), or
Admn 3 (29 injections or 6-9 oral gavages). Radiation doses ranged from LD30/30
to LD95/30. Thirty-day survival of vehicle controls in each group was used to
construct radiation dose lethality response relationship (DRR) probit plots,
which were compared statistically to the original DRR from which all LDXX/30 for
the studies were obtained. The slope of the Admn 3 probit was found to be
significantly steeper (5.190) than that of the original DRR (2.842) or Admn 2
(2.009), which were not significantly different. The LD50/30 for Admn 3 (8.43 Gy)
was less than that of the original DRR (8.53 Gy, p < 0.050), whereas the LD50/30
of other groups were similar. Kaplan-Meier survival curves showed significantly
worse survival of Admn 3 mice compared to the three other groups (p = 0.007).
Taken together, these results show that stressful administration schedules of MCM
can negatively impact survival and that dosing regimens should be considered when
constructing DRR to use in survival studies.
PMID- 26425901
TI - The Delayed Effects of Acute Radiation Syndrome: Evidence of Long-Term Functional
Changes in the Clonogenic Cells of the Small Intestine.
AB - Long term or residual damage post-irradiation has been described for many
tissues. In hematopoietic stem cells (HSC), this is only revealed when the HSC
are stressed and required to regenerate and repopulate a myeloablated host. Such
an assay cannot be used to assess the recovery potential of previously irradiated
intestinal stem cells (ISC) due to their incompatibility with transplantation.
The best approximation to the HSC assay is the crypt microcolony assay, also
based on clonogen survival. In the current study, the regenerative capacity of
intestinal clonogenic cells in mice that had survived 13 Gy irradiation (with 5%
bone marrow shielding to allow survival through the hematopoietic syndrome) and
were then aged for 200 d was compared to previously unirradiated age-matched
controls. Interestingly, at 200 d following 13 Gy, there remained a statistically
significant reduction in crypts present in the various small intestinal regions
(illustrating that the gastrointestinal epithelium had not fully recovered
despite the 200-d interval). However, upon re-irradiation on day 196, those mice
previously irradiated had improved crypt survival and regeneration compared to
the age-matched controls. This was evident in all regions of the small intestine
following 11-13 Gy re-exposure. Thus, there were either more clonogens per crypt
within those previously irradiated and/or those that were present were more
radioresistant (possibly because a subpopulation was more quiescent). This is
contrary to the popular belief that previously irradiated animals may have an
impaired/delayed regenerative response and be more radiosensitive.
PMID- 26425902
TI - Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X
Irradiation.
AB - Recovery from severe immunosuppression requires hematopoietic stem cell
reconstitution and effective thymopoiesis to restore a functional immune cell
repertoire. Herein, a model of immune cell reconstitution consequent to
potentially lethal doses of irradiation is described, which may be valuable in
evaluating potential medical countermeasures. Male rhesus macaques were total
body irradiated by exposure to 6.00 Gy 250 kVp x-radiation (midline tissue dose,
0.13 Gy min), resulting in an approximate LD10/60 (n = 5/59). Animals received
medical management, and hematopoietic and immune cell recovery was assessed (n <=
14) through 370 d post exposure. A subset of animals (n <= 8) was examined
through 700 d. Myeloid recovery was assessed by neutrophil and platelet-related
parameters. Lymphoid recovery was assessed by the absolute lymphocyte count and
FACS-based phenotyping of B- and T-cell subsets. Recent thymic emigrants were
identified by T cell receptor excision circle quantification. Severe neutropenia,
lymphopenia, and thrombocytopenia resolved within 30 d. Total CD3+ cells MUL
required 60 d to reach values 60% of normal, followed by subsequent slow recovery
to approximately normal by 180 d post irradiation. Recovery of CD3+4+ and CD3+8+
cell memory and naive subsets were markedly different. Memory populations were >=
100% of normal by day 60, whereas naive populations were only 57% normal at 180 d
and never fully recovered to baseline post irradiation. Total (CD20+) B cells MUL
were within normal levels by 77 d post exposure. This animal model elucidates the
variable T- and B-cell subset recovery kinetics after a potentially lethal dose
of total-body irradiation that are dependent on marrow-derived stem and
progenitor cell recovery, peripheral homeostatic expansion, and thymopoiesis.
PMID- 26425903
TI - The Effect of Radiation Dose and Variation in Neupogen(r) Initiation Schedule on
the Mitigation of Myelosuppression during the Concomitant GI-ARS and H-ARS in a
Nonhuman Primate Model of High-dose Exposure with Marrow Sparing.
AB - A nonhuman primate (NHP) model of acute high-dose, partial-body irradiation with
5% bone marrow (PBI/BM5) sparing was used to assess the effect of Neupogen(r)
[granulocyte colony stimulating factor (G-CSF)] to mitigate the associated
myelosuppression when administered at an increasing interval between exposure and
initiation of treatment. A secondary objective was to assess the effect of
Neupogen(r) on the mortality or morbidity of the hematopoietic (H)- acute
radiation syndrome (ARS) and concurrent acute gastrointestinal radiation syndrome
(GI-ARS). NHP were exposed to 10.0 or 11.0 Gy with 6 MV LINAC-derived photons at
approximately 0.80 Gy min. All NHP received medical management. NHP were dosed
daily with control article (5% dextrose in water) initiated on day 1 post
exposure or Neupogen(r) (10 MUg kg) initiated on day 1, day 3, or day 5 until
recovery [absolute neutrophil count (ANC) >= 1,000 cells MUL for three
consecutive days]. Mortality in both the 10.0 Gy and 11.0 Gy cohorts suggested
that early administration of Neupogen(r) at day 1 post exposure may affect acute
GI-ARS mortality, while Neupogen(r) appeared to mitigate mortality due to the H
ARS. However, the study was not powered to detect statistically significant
differences in survival. The ability of Neupogen(r) to stimulate granulopoiesis
was assessed by evaluating key parameters for ANC recovery: the depth of nadir,
duration of neutropenia (ANC < 500 cells MUL) and recovery time to ANC >= 1,000
cells MUL. Following 10.0 Gy PBI/BM5, the mean duration of neutropenia was 11.6 d
in the control cohort vs. 3.5 d and 4.6 d in the day 1 and day 3 Neupogen(r)
cohorts, respectively. The respective ANC nadirs were 94 cells MUL, 220 cells
MUL, and 243 cells MUL for the control and day 1 and day 3 Neupogen(r) cohorts.
Following 11.0 Gy PBI/BM5, the duration of neutropenia was 10.9 d in the control
cohort vs. 2.8 d, 3.8 d, and 4.5 d in the day 1, day 3, and day 5 Neupogen(r)
cohorts, respectively. The respective ANC nadirs for the control and day 1, day
3, and day 5 Neupogen(r) cohorts were 131 cells MUL, 292 cells MUL, 236 cells
MUL, and 217 cells MUL, respectively. Therefore, the acceleration of
granulopoiesis by Neupogen(r) in this model is independent of the time interval
between radiation exposure and treatment initiation up to 5 d post-exposure. The
PBI/BM5 model can be used to assess medical countermeasure efficacy in the
context of the concurrent GI- and H-ARS.
PMID- 26425904
TI - Citrulline as a Biomarker in the Non-human Primate Total- and Partial-body
Irradiation Models: Correlation of Circulating Citrulline to Acute and Prolonged
Gastrointestinal Injury.
AB - The use of plasma citrulline as a biomarker for acute and prolonged
gastrointestinal injury via exposure to total- and partial-body irradiation (6 MV
LINAC-derived photons; 0.80 Gy min) in nonhuman primate models was investigated.
The irradiation exposure covered gastrointestinal injuries spanning lethal, mid
lethal, and sub-lethal doses. The acute gastrointestinal injury was assessed via
measurement of plasma citrulline and small intestinal histopathology over the
first 15 d following radiation exposure and included total-body irradiation at
13.0 Gy, 10.5 Gy, and 7.5 Gy and partial-body irradiation at 11.0 Gy with 5% bone
marrow sparing. The dosing schemes of 7.5 Gy total-body irradiation and 11.0 Gy
partial-body irradiation included time points out to day 60 and day 180,
respectively, which allowed for correlation of plasma citrulline to prolonged
gastrointestinal injury and survival. Plasma citrulline values were radiation
dependent for all radiation doses under consideration, with nadir values ranging
from 63-80% lower than radiation-naive NHP plasma. The nadir values were observed
at day 5 to 7 post irradiation. Longitudinal plasma citrulline profiles
demonstrated prolonged gastrointestinal injury resulting from acute high-dose
irradiation had long lasting effects on enterocyte function. Moreover, plasma
citrulline did not discriminate between total-body or partial-body irradiation
over the first 15 d following irradiation and was not predictive of survival
based on the radiation models considered herein.
PMID- 26425905
TI - Citrulline as a Biomarker in the Murine Total-Body Irradiation Model: Correlation
of Circulating and Tissue Citrulline to Small Intestine Epithelial
Histopathology.
AB - The use of plasma citrulline as a biomarker for gastrointestinal acute radiation
syndrome via exposure to total-body irradiation in a murine model was
investigated. The radiation exposure covered lethal, mid-lethal, and sub-lethal
gastrointestinal acute radiation syndrome. Plasma citrulline profiles were
generated over the first 6 d following total-body irradiation exposure of 6-15
Gy. In addition, plasma citrulline was comprehensively evaluated in the context
of matching small intestine citrulline and histopathology. Higher plasma
citrulline was significantly associated with lower irradiation doses over the
first 6 d following the irradiation insult. Furthermore, higher plasma citrulline
was significantly associated with higher crypt survival. The correlation of the
plasma citrulline to crypt survival was more robust for higher irradiation doses
and for later time points. The data suggested plasma citrulline was most
informative for reflecting gastrointestinal injury resulting from exposure to 9
15 Gy total-body irradiation covering time-points 2-5 d post the irradiation
insult.
PMID- 26425906
TI - A MALDI-MSI Approach to the Characterization of Radiation-Induced Lung Injury and
Medical Countermeasure Development.
AB - Radiation-induced lung injury is highly complex and characterized by multiple
pathologies, which occur over time and sporadically throughout the lung. This
complexity makes biomarker investigations and medical countermeasure screenings
challenging. Matrix-assisted laser desorption/ionization mass spectrometry
imaging (MALDI-MSI) has the ability to resolve differences spatially in molecular
profiles within the lung following radiation exposure and can aid in biomarker
identification and pharmaceutical efficacy investigations. MALDI-MSI was applied
to the investigation of a whole-thorax lung irradiation model in non-human
primates (NHP) for lipidomic analysis and medical countermeasure distribution.
PMID- 26425907
TI - The Evolving Mcart Multimodal Imaging Core: Establishing a Protocol for Computed
Tomography and Echocardiography in the Rhesus Macaque to Perform Longitudinal
Analysis of Radiation-Induced Organ Injury.
AB - Computed Tomography (CT) and Echocardiography (EC) are two imaging modalities
that produce critical longitudinal data that can be analyzed for radiation
induced organ-specific injury to the lung and heart. The Medical Countermeasures
Against Radiological Threats (MCART) consortium has a well established animal
model research platform that includes nonhuman primate (NHP) models of the acute
radiation syndrome and the delayed effects of acute radiation exposure. These
models call for a definition of the latency, incidence, severity, duration, and
resolution of different organ-specific radiation-induced subsyndromes. The
pulmonary subsyndromes and cardiac effects are a pair of interdependent syndromes
impacted by exposure to potentially lethal doses of radiation. Establishing a
connection between these will reveal important information about their
interaction and progression of injury and recovery. Herein, the authors
demonstrate the use of CT and EC data in the rhesus macaque models to define
delayed organ injury, thereby establishing: a) consistent and reliable
methodology to assess radiation-induced damage to the lung and heart; b) an
extensive database in normal age-matched NHP for key primary and secondary
endpoints; c) identified problematic variables in imaging techniques and proposed
solutions to maintain data integrity; and d) initiated longitudinal analysis of
potentially lethal radiation-induced damage to the lung and heart.
PMID- 26425908
TI - Comparing the Hematopoetic Syndrome Time Course in the NHP Animal Model to
Radiation Accident Cases From the Database Search.
AB - Since controlled clinical studies on drug administration for the acute radiation
syndrome are lacking, clinical data of human radiation accident victims as well
as experimental animal models are the main sources of information. This leads to
the question of how to compare and link clinical observations collected after
human radiation accidents with experimental observations in non-human primate
(NHP) models. Using the example of granulocyte counts in the peripheral blood
following radiation exposure, approaches for adaptation between NHP and patient
databases on data comparison and transformation are introduced. As a substitute
for studying the effects of administration of granulocyte-colony stimulating
factor (G-CSF) in human clinical trials, the method of mathematical modeling is
suggested using the example of G-CSF administration to NHP after total body
irradiation.
PMID- 26425909
TI - An Interlaboratory Validation of the Radiation Dose Response Relationship (DRR)
for H-ARS in the Rhesus Macaque.
AB - The Medical Countermeasures against Radiological Threats (MCART) consortium has
established a dose response relationship for the hematopoietic acute radiation
syndrome (HARS) in the rhesus macaque conducted under an individualized
supportive care protocol, including blood transfusions. Application of this
animal model as a platform for demonstrating efficacy of candidate medical
countermeasures is significantly strengthened when the model is independently
validated at multiple institutions. The study reported here describes
implementation of standard operating procedures at an institute outside the
consortium in order to evaluate the ability to establish an equivalent radiation
dose response relationship in a selected species. Validation of the animal model
is a significant component for consideration of the model protocol as an FDA
recommended drug development tool in the context of the "Animal Rule." In the
current study, 48 male rhesus macaques (4-8 kg) were exposed to total-body
irradiation (TBI) using 6 MV photon energy at a dose rate of approximately 0.8 Gy
min. Results show that onset and duration of the hematological response,
including anemia, neutropenia, and thrombocytopenia, following TBI ranging from
6.25 to 8.75 Gy correlate well with previously reported findings. The lethality
values at 60 d following TBI were estimated to be 6.88 Gy (LD30/60), 7.43 Gy
(LD50/60), and 7.98 Gy (LD70/60). These values are equivalent to those published
previously of 7.06 Gy (LD30/60), 7.52 Gy (LD50/60), and 7.99 Gy (LD70/60); the
DRR slope (p = 0.68) and y-intercepts show agreement along the complete dose
range for HARS. The ability to replicate the previously established institutional
lethality profile (PROBIT) and model outcomes through careful implementation of
defined procedures is a testament to the robustness of the model and highlights
the need for consistency in procedures.
PMID- 26425910
TI - Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS:
Multiple-Organ Injury Consequent to <10 Gy Total Body Irradiation.
AB - The threat of radiation exposure from warfare or radiation accidents raises the
need for appropriate animal models to study the acute and chronic effects of high
dose rate radiation exposure. The goal of this study was to assess the late
development of fibrosis in multiple organs (kidney, heart, and lung) in survivors
of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS).
Separate groups of mice for histological and functional studies were exposed to a
single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a
Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were
elevated significantly in the irradiated mice at 9 and 21 mo (from ~22 to 34 +/-
3.8 and 69 +/- 6.0 mg dL, p < 0.01 vs. non-irradiated controls) and correlated
with glomerosclerosis (29 +/- 1.8% vs. 64 +/- 9.7% of total glomeruli, p < 0.01
vs. non-irradiated controls). Glomerular tubularization and hypertrophy and
tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An
increase in interstitial, perivascular, pericardial and peribronchial
fibrosis/collagen deposition was observed from ~9-21 mo post-TBI in kidney,
heart, and lung of irradiated mice relative to age-matched controls.
Echocardiography suggested decreased ventricular volumes with a compensatory
increase in the left ventricular ejection fraction. The results indicate that
significant delayed effects of acute radiation exposure occur in kidney, heart,
and lung in survivors of the murine H-ARS TBI model, which mirrors pathology
detected in larger species and humans at higher radiation doses focused on
specific organs.
PMID- 26425916
TI - Fibrinolytic system related to pulmonary arterial pressure and lung function of
patients with idiopathic pulmonary fibrosis.
AB - OBJECTIVES AND AIMS: To investigate urokinase-(uPA) and tissue-type (tPA)
plasminogen activator and plasminogen activator inhibitor type-1 (PAI-1) levels
in patients with idiopathic pulmonary fibrosis (IPF) and to determine the
relationship between fibrinolytic system and pulmonary arterial pressure and
pulmonary function. METHODS: Seventy-nine patients with IPF were included.
Bronchoalveolar lavage fluid (BALF) and blood samples were collected. The
concentrations of tPA, uPA and PAI-1 were measured using enzyme-linked
immunosorbent assay. Doppler echocardiography was used to detect tricuspid
regurgitation pressure gradient (TRPG) to estimate pulmonary arterial pressure.
RESULTS: BALF tPA elevated (P < 0.005), circulatory PAI-1 decreased (P = 0.05)
and the ratio of uPA and PAI-1 decreased (P = 0.01) in BALF in IPF patients with
pulmonary hypertension (PH) compared to those without PH. Positive linear
correlations were found: BALF tPA and TRPG (r = 0.558, P = 0.013); the predicted
percentage of diffusion capacity of lung for carbon monoxide adjustments for
alveolar volume and BALF uPA (r = 0.319, P = 0.035). Negative linear correlations
were as follows: BALF PAI-1 and the predicted percentage of VCmax (r = -0.325, P
= 0.020), or total lung capacity (r = -0.312, P = 0.033); circulatory PAI-1 and
TRPG (r = -0.697, P = 0.003). CONCLUSIONS: The change of alveolar fibrolytic
system in IPF, especially the uPA reduction and the PAI-1elevation, contributes
to the deterioration of lung function. During the lung injury initiating
fibrosis, tPA and PAI-1 might be leaked out of the pulmonary capillaries into
alveoli, resulting in their elevation in alveoli and reduction in circulation,
and finally contributing to the development of PH in IPF.
PMID- 26425917
TI - Comparative study of reproductive skew and pair-bond stability using genealogies
from 80 small-scale human societies.
AB - OBJECTIVES: Genealogies contain information on the prevalence of different
sibling types that result from past reproductive behavior. Full sibling sets stem
from stable monogamy, paternal half siblings primarily indicate male reproductive
skew, and maternal half siblings reflect unstable pair bonds. METHODS: Full and
half sibling types are calculated for a total of 61,181 siblings from published
genealogies for 80 small-scale societies, including foragers, horticulturalists,
agriculturalists, and pastoralists from around the world. RESULTS: Most siblings
are full (61%) followed by paternal half siblings (27%) and maternal half
siblings (13%). Paternal half siblings are positively correlated with more
polygynous marriages, higher at low latitudes, and slightly higher in
nonforagers, Maternal half sibling fractions are slightly higher at low latitudes
but do not vary with subsistence. Partible paternity societies in Amazonia have
more paternal half siblings indicating higher male reproductive skew.
CONCLUSIONS: Sibling counts from genealogies provide a convenient method to
simultaneously investigate the reproductive skew and pair-bond stability
dimensions of human mating systems cross-culturally. Am. J. Hum. Biol. 28:335
342, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26425918
TI - Chiral Inhibition of Rivaroxaban Derivatives Towards UDP-Glucuronosyltransferase
(UGT) Isoforms.
AB - Rivaroxaban is an oral direct factor Xa (FXa) inhibitor clinically used to
prevent and treat thromboembolic disorders. Drug-drug interaction (DDI) exist for
rivaroxaban and the inhibitors of CYP3A4/5. This study aims to investigate the
inhibition of rivaroxaban and its derivatives with a chiral center towards UDP
glucuronosyltransferases (UGTs). Chemical synthesis was performed to obtain
rivaroxaban derivatives with different chiral centers. UGTs supersomes-catalyzed
4-methylumbelliferone (4-MU) glucuronidation was employed to evaluate the
inhibition potential towards various UGT isoforms. A significant influence of
rivaroxaban derivatives towards UGT1A3 was observed. Chiral centers produce
different effects towards the effect of four pairs of rivaroxaban derivatives
towards UGT1A3 activity, with stronger inhibition potential of S1 than R1, but
stronger inhibition capability of R2, R3, R4 than S2, S3, and S4. Competitive
inhibition of R3 and R4 towards UGT1A3 was demonstrated by Dixon and Lineweaver
Burk plots. In conclusion, the significant influence of rivaroxaban derivatives
towards UGT1A3's activity was demonstrated in the present study. The chirality
centers highly affected the inhibition behavior of rivaroxaban derivatives
towards UGT1A3.
PMID- 26425919
TI - Transcatheter aortic valve replacement for native aortic valve regurgitation as a
bridge to liver transplantation.
AB - Coexistence of end-stage liver disease (ESLD) and severe valvular heart disease
conveyed substantial risk for patients, oftentimes leading to exclusion from
liver transplantation candidacy due to inability to safely offer cardiac surgery
prior to transplantation. Several approaches have been described, including
performing transplantation and valve surgery concurrently, or in sequence. Both
options, however, have associated complications: catastrophic repercussion of
peri-operative coagulopathy and organ dysfunction post-transplantation,
respectively. The introduction of transcatheter procedures offered a safer
alternative for high-risk patients; however, its recognized indications remained
limited. A novel approach to this surgical dilemma by performing transcatheter
aortic valve replacement (TAVR) for severe native aortic valve regurgitation in a
patient on the liver transplant list has been presented. The procedure proved to
be an effective management for the aortic valve insufficiency, improving our
patient's hemodynamics in preparation for the subsequent orthotopic liver
transplantation (OLT). (c) 2015 Wiley Periodicals, Inc.
PMID- 26425920
TI - Comparing two survey methods of measuring health-related indicators: Lot Quality
Assurance Sampling and Demographic Health Surveys.
AB - OBJECTIVES: Two common methods used to measure indicators for health programme
monitoring and evaluation are the demographic and health surveys (DHS) and lot
quality assurance sampling (LQAS); each one has different strengths. We report on
both methods when utilised in comparable situations. METHODS: We compared 24
indicators in south-west Uganda, where data for prevalence estimations were
collected independently for the two methods in 2011 (LQAS: n = 8876; DHS: n =
1200). Data were stratified (e.g. gender and age) resulting in 37 comparisons. We
used a two-sample two-sided Z-test of proportions to compare both methods.
RESULTS: The average difference between LQAS and DHS for 37 estimates was 0.062
(SD = 0.093; median = 0.039). The average difference among the 21 failures to
reject equality of proportions was 0.010 (SD = 0.041; median = 0.009); among the
16 rejections, it was 0.130 (SD = 0.010, median = 0.118). Seven of the 16
rejections exhibited absolute differences of <0.10, which are clinically (or
managerially) not significant; 5 had differences >0.10 and <0.20 (mean = 0.137,
SD = 0.031) and four differences were >0.20 (mean = 0.261, SD = 0.083).
CONCLUSION: There is 75.7% agreement across the two surveys. Both methods yield
regional results, but only LQAS provides information at less granular levels
(e.g. the district level) where managerial action is taken. The cost advantage
and localisation make LQAS feasible to conduct more frequently, and provides the
possibility for real-time health outcomes monitoring.
PMID- 26425921
TI - The effect of a low radiation CT protocol on accuracy of CT guided implant
migration measurement: A cadaver study.
AB - The current study compared the impact of low radiation CT protocols on the
accuracy, repeatability, and inter- and intra-observer variability of implant
migration studies in total hip arthroplasty. Two total hip replacements were
performed in two human cadavers and six tantalum beads were inserted into the
femur similar to radiostereometric analysis. Six different 28 mm heads (-3 mm, 0
mm, 2.5 mm, 5.0 mm, 7.5 mm, and 10 mm) were added to simulate five reproducible
translations (maximum total point migration) of the center of the head. Three CT
scans with varying levels of radiation were performed for each head position. The
effective dose (mSv) was 3.8 mSv for Protocol A (standard protocol), 0.7 mSv for
Protocol B and 1.6 mSv for Protocol C. Implant migration was measured in a 3-D
analysis software (Geomagic Studio 7). The accuracy was 0.16 mm for CT Protocol
A, 0.13 mm for Protocol B and 0.14 mm for Protocol C; The repeatability was 0.22
mm for CT Protocol A, 0.18 mm for Protocol B and 0.20 mm for Protocol C; ICC for
inter observer reliability was 0.89, intra observer reliability was 0.95. The
difference in accuracy between standard protocol A and the two low radiation
protocols (B, C) was less than 0.05 mm. The accuracy, inter- and intra-observer
reliability of all three CT protocols is comparable to radiostereometric
analysis. Reducing the CT radiation exposure to numbers similar to an AP Pelvis
radiograph (0.7 mSv protocol B) does not affect the accuracy of implant migration
measurements.
PMID- 26425922
TI - Bioelectrical impedance vector analysis for evaluating zinc supplementation in
prepubertal and healthy children.
AB - BACKGROUND: The prevalence of abnormal nutritional status has increased in
children and adolescents. Nutritional assessment is important for monitoring the
health and nutritional status. Bioelectrical impedance vector analysis (BIVA)
combines changes in tissue hydration and structure and body composition that can
be assessed. OBJECTIVES: The objective of this study was to use BIVA to evaluate
nutritional status in 60 prepubertal children, aged between 8 and 9 years,
supplemented with zinc, to detect possible changes in body composition. DESIGN:
We performed a randomized, controlled, triple-blind study. The children were
divided into the control group (CG; sorbitol 10%, n=29) or the experimental group
(EG; 10 mg Zn/day, n=31), and the duration of the experiment was 3 months.
Anthropometric assessments were performed for all of the children. RESULTS: The
body mass index-for-age increased after oral zinc supplementation in the EG
(p=0.005). BIVA indicated that the CG demonstrated a tendency for dehydration and
decreased soft tissue and the EG demonstrated a tendency for increased soft
tissue, primarily the fat-free mass. After analyses of BIVA ellipses, we observed
that this method could detect improvements in body composition in healthy
children supplemented with zinc. CONCLUSIONS: These results suggest that BIVA
could be an auxiliary method for studying a small population undergoing zinc
intervention.
PMID- 26425923
TI - Phenolic Acid-based Poly(anhydride-esters) as Antioxidant Biomaterials.
AB - Poly(anhydride-esters) comprised of naturally occurring, non-toxic phenolic
acids, namely syringic and vanillic acid, with antioxidant properties were
prepared via solution polymerization methods. Polymer and polymer precursor
physiochemical properties were characterized, including polymer molecular weight
and thermal properties. In vitro release studies illustrated that polymer
hydrolytic degradation was influenced by relative hydrophobicity and degree of
methoxy substitution of the phenolic acids. Further, the released phenolic acids
were found to maintain antioxidant potency relative to free phenolic acid
controls as determined by a 2,2-diphenyl-1-picrylhydrazyl assay. Polymer
cytotoxicity was assessed with L929 fibroblasts in polymer-containing media;
appropriate cell morphology and high fibroblast proliferation were obtained for
the polymers at the lower concentrations. These polymers deliver non-cytotoxic
levels of naturally occurring antioxidants, which could be efficacious in topical
delivery of antioxidant therapies.
PMID- 26425924
TI - Time-Resolved Proteomic Visualization of Dendrimer Cellular Entry and
Trafficking.
AB - Our understanding of the complex cell entry pathways would greatly benefit from a
comprehensive characterization of key proteins involved in this dynamic process.
Here we devise a novel proteomic strategy named TITAN (Tracing Internalization
and TrAfficking of Nanomaterials) to reveal real-time protein-dendrimer
interactions using a systems biology approach. Dendrimers functionalized with
photoreactive cross-linkers were internalized by HeLa cells and irradiated at set
time intervals, then isolated and subjected to quantitative proteomics. In total,
809 interacting proteins cross-linked with dendrimers were determined by TITAN in
a detailed temporal manner during dendrimer internalization, traceable to at
least two major endocytic mechanisms, clathrin-mediated and caveolar/raft
mediated endocytosis. The direct involvement of the two pathways was further
established by the inhibitory effect of dynasore on dendrimer uptake and changes
in temporal profiles of key proteins.
PMID- 26425926
TI - High mobility, large linear magnetoresistance, and quantum transport phenomena in
Bi2Te3 films grown by metallo-organic chemical vapor deposition (MOCVD).
AB - We investigated the magnetotransport properties of Bi2Te3 films grown on GaAs
(001) substrate by a cost-effective metallo-organic chemical vapor deposition
(MOCVD). We observed the remarkably high carrier mobility and the giant linear
magnetoresistance (carrier mobility ~ 22 000 cm(2) V(-1) s(-1), magnetoresistance
~ 750% at 1.8 K and 9 T for a 100 nm thick film) that depends on the film
thickness. In addition, the Shubnikov-de Haas oscillation was observed, from
which the effective mass was calculated to be consistent with the known value.
From the thickness dependence of the Shubnikov-de Haas oscillation, it was found
that a two dimensional electron gas with the conventional electron nature
coexists with the topological Dirac fermion states and dominates the carrier
transport in the Bi2Te3 film with thickness higher than 300 nm. These results are
attributed to the intrinsic nature of Bi2Te3 in the high-mobility transport
regime obtained by a deliberate choice of the substrate and the growth
conditions.
PMID- 26425925
TI - Dental maturation, eruption, and gingival emergence in the upper jaw of newborn
primates.
AB - In this report we provide data on dental eruption and tooth germ maturation at
birth in a large sample constituting the broadest array of non-human primates
studied to date. Over 100 perinatal primates, obtained from natural captive
deaths, were screened for characteristics indicating premature birth, and were
subsequently studied using a combination of histology and micro-CT. Results
reveal one probable unifying characteristic of living primates: relatively
advanced maturation of deciduous teeth and M1 at birth. Beyond this, there is
great diversity in the status of tooth eruption and maturation (dental stage) in
the newborn primate. Contrasting strategies in producing a masticatory battery
are already apparent at birth in strepsirrhines and anthropoids. Results show
that dental maturation and eruption schedules are potentially independently co
opted as different strategies for attaining feeding independence. The most common
strategy in strepsirrhines is accelerating eruption and the maturation of the
permanent dentition, including replacement teeth. Anthropoids, with only few
exceptions, accelerate mineralization of the deciduous teeth, while delaying
development of all permanent teeth except M1. These results also show that no
living primate resembles the altricial tree shrew (Tupaia) in dental development.
Our preliminary observations suggest that ecological explanations, such as diet,
provide an explanation for certain morphological variations at birth. These
results confirm previous work on perinatal indriids indicating that these and
other primates telegraph their feeding adaptations well before masticatory
anatomy is functional. Quantitative analyses are required to decipher specific
dietary and other influences on dental size and maturation in the newborn
primate.
PMID- 26425927
TI - The impact of a cancer diagnosis on health and well-being: a prospective,
population-based study.
AB - OBJECTIVE: Little is known about the trajectory of health and well-being from
before to after a cancer diagnosis. This study aimed to examine changes in health
and well-being across three time points (0-2 years before a cancer diagnosis, 0-2
years post-diagnosis and 2-4 years post-diagnosis) in individuals receiving a new
cancer diagnosis, and at matched time points in a cancer-free comparison group.
METHODS: Data were from waves 1-6 of the English Longitudinal Study of Ageing.
Repeated-measures ANOVAs were used to examine differences in self-rated health,
mobility impairments, activities of daily living impairments, quality of life,
depressive symptoms and life satisfaction by group and time, and group-by-time
interactions. RESULTS: Of the 4565 participants with data from three time points,
444 (9.7%) reported a new cancer diagnosis. Those in the cancer group reported
poorer self-rated health (p < .001), quality of life (p < .001) and life
satisfaction (p < .01) than participants in the comparison group, and a higher
proportion reported depressive symptoms (p < .001) and impairments in mobility (p
< .001) and activities of daily living (p < .001). All markers of health and well
being worsened significantly over time. The group-by-time interaction was
significant for self-rated health (p < .001), with a greater decline in health
over time in the cancer group. CONCLUSIONS: Cancer survivors in this sample had
poorer health and well-being than those with no diagnosis, and self-rated health
deteriorated more rapidly following a cancer diagnosis. Screening for these
factors around the time of a cancer diagnosis could allow for interventions to be
targeted effectively and improve the health and well-being of cancer survivors.
(c) 2015 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.
PMID- 26425928
TI - Referential Ambiguity in the Narrative Productions of African American Adults.
AB - PURPOSE: The purpose of this study was to examine the production of referential
ambiguities in two contrasting narrative conditions among age-defined groups of
healthy African American women. METHOD: Twenty middle-aged adults (M = 51 years)
and 20 older adults (M = 72 years) produced a complex story retelling and a
personal narrative. All narratives were transcribed orthographically, parsed into
T-units, and analyzed for surface structure markings of referents and the
presence of ambiguities. RESULTS: The results demonstrated that older adults
produced more ambiguities than middle-aged adults, were more compromised with
task complexity, used more role or relation designations to refer to story
characters while underusing proper names, and exhibited significant lexical
retrieval deficits during ongoing narrative production. Middle-aged adults
produced more proper names, but were also challenged by the complexity of the
story-retelling task. Moreover, the results showed that older adults produced
more African American English variants than middle-aged adults. CONCLUSION: This
investigation revealed a pattern of age-related ambiguities during narrative
production. The results demonstrated that lexical retrieval from long-term
semantic memory was an important predictor of ambiguity, whereas African American
English contributed negligibly. These results show that referential ambiguities
may be a robust characteristic of cognitive-linguistic changes that occur with
typical aging.
PMID- 26425929
TI - The effect of training in mindfulness and affect consciousness on the therapeutic
environment for patients with psychoses: an explorative intervention study.
AB - RATIONALE: The ward atmosphere and the relationships between patients and staff
contribute to the improvement in symptoms and psychiatric patient functioning and
satisfaction. The quality of the therapeutic relationship is connected to the
degree of self-reflection and self-awareness by the staff. OBJECTIVE: To examine
the effect of two different training programmes for healthcare professionals on
the ward atmosphere in wards for psychotic patients. DESIGN AND METHODS:
Exploratory intervention study with two eight-week interventions of mindfulness
training and affect-consciousness training. The outcome was measured on
mindfulness and on relevant subscales of the Ward Atmosphere Scale. Data were
collected by means of questionnaires and analysed using paired samples t-tests
and repeated measures anova. RESULTS: Two groups professionals (n = 27 & n = 23)
participated in the study. Improvements indicated that both interventions had a
positive impact on the ward atmosphere. STUDY LIMITATIONS: The exploratory design
and the small samples size make definitive conclusions difficult. Patient
assessment on the ward atmosphere scale would have strengthened the validity of
the results. CONCLUSION: The ward atmosphere in two different wards for psychotic
patients improved after staff training in mindfulness or affect consciousness.
There were differences in change profiles for the groups in accordance with the
differences in the two interventions. PRACTICE IMPLICATIONS: We recommend
awareness on the quality of the ward atmosphere in wards for psychotic patients.
Both training in mindfulness and affect consciousness can support healthcare
professionals in their awareness.
PMID- 26425930
TI - Serotonergic or Anticholinergic Toxidrome: Case Report of a 9-Year-Old Girl.
AB - OBJECTIVE: The aim of this study was to report an acute onset of symptoms
erroneously attributed to serotonin syndrome in a child who had been given both
anticholinergic and serotonergic agents. CASE SUMMARY: A 9-year-old girl with
chronic anxiety and gastrointestinal problems was prescribed oral sertraline 6.25
mg daily, as well as hyoscyamine, ondansetron, montelukast, and a course of
nitazoxanide. She was also routinely given diphenhydramine and omeprazole. Three
days after increasing sertraline to 12.5 mg, she presented to the emergency
department with altered mental status, hallucinations, mydriasis, tachycardia,
and pyrexia. She was admitted to the pediatric intensive care unit and
subsequently treated unsuccessfully for serotonin syndrome, with blurred vision
and clonus persisting at discharge 4 days after admittance. Upon follow-up with
her outpatient clinic, all anticholinergic agents were discontinued, and symptoms
slowly resolved. CONCLUSIONS: This case illustrates the importance of
differential diagnosis between toxidromes and how clinical presentation can be
altered by preexisting conditions as well as the use of medications that affect
multiple neurotransmitter systems.
PMID- 26425931
TI - Child Abuse Mimic: Avulsion Injury in a Child With Penoscrotal Webbing.
AB - Sexual abuse of children is prevalent in today's society. In 2012, approximately
686,000 children (9.2 per 1000) in the United States were determined to be
victims of substantiated child abuse and neglect, according to national data
compiled by child protective service agencies; victimization rates were highest
for children younger than 1 year. Nearly 9.3% of maltreated children were victims
of sexual abuse, this finding was reported by US Department of Health and Human
Services (http://www.acf.hhs.gov/programs/cb/research-data-technology/statistics
research/child-maltreatment). Previous research has shown that as many as 1 in 3
girls and 1 in 7 boys will be sexually abused during childhood (Child Abuse Negl.
2003;27:1205-1222). Although sexual abuse seems to be less common in boys than
girls, this may be partly due to underdiagnosis and underreporting of sexual
abuse in boys (Arch Dis Child. 2007;92:328-331). Clinicians should therefore
consider the possibility of sexual abuse when boys present with genital injuries,
because failing to recognize and diagnose sexual abuse can pose an ongoing safety
risk to a child. However, an erroneous diagnosis of sexual abuse can have equally
hazardous repercussions, including removal of a child from their caregivers or
prosecution of an innocent individual. A number of medical conditions can mimic
child sexual abuse injuries, including anal fissures, failure of midline fusion,
perianal streptococcal dermatitis, and straddle injury (J Pediatr Health Care.
2009;23:283-288 and Acta Paediatr. 2011;100:590-593). The following case involves
a 5-week-old male infant who presented to the pediatric emergency department with
an avulsion injury to his penis concerning for sexual abuse. He was ultimately
diagnosed with a relatively rare anatomic variant of the genitalia and determined
to have sustained an accidental injury whose appearance mimicked abuse.
PMID- 26425932
TI - Ultrasound-Assisted Lumbar Puncture in Pediatric Emergency Department.
AB - BACKGROUND: Lumbar puncture (LP) is one of the essential diagnostic tools in
pediatric emergency services. Recently, ultrasound-assisted LP was reported to be
beneficial in the emergency service by facilitating the procedure and improving
the successful procedure rates. In addition, this method may be effective in
reducing patient and parent anxiety due to the LP procedure. OBJECTIVES: The aim
of this study was to investigate the effect of ultrasound-assisted LP on the
outcomes of puncture procedures and traumatic LP. METHODS: The study included
patients younger than 18 years, who were admitted to the pediatric emergency
service and underwent LP because of suspected central nervous system infection.
The patients requiring LP were randomly divided into 2 groups designated as odd
and even. One group received LP using the conventional method, whereas the other
group had LP after spinal space measurement by ultrasound. The patients who did
and who did not undergo ultrasound-assisted LP were compared for demographics,
number of puncture attempts, and traumatic LP. Statistical analysis was performed
using the Mann-Whitney U test and the Student t test. The chi test was used when
nominal data were compared between the 2 groups. RESULTS: Ultrasound-assisted LP
was performed in 56 patients, and LP by using conventional method was performed
in 55 patients. There was traumatic LP in 5 (8.9%) of the patients who underwent
ultrasound-assisted LP and 9 (16.3%) of the patients who underwent LP using the
conventional method (P > 0.05). The number of puncture attempts was 2 or more in
2 (3.5%) of the patients who underwent ultrasound-assisted LP and 5 (9%) of the
patients who had LP using the conventional method (P > 0.05). CONCLUSIONS:
Ultrasound-assisted LP reduced traumatic LP and the number of puncture attempts
in pediatric patients; however, the results were not statistically significant.
PMID- 26425933
TI - An imputation-based genome-wide association study on traits related to male
reproduction in a White Duroc * Erhualian F2 population.
AB - Boar reproductive traits are economically important for the pig industry. Here we
conducted a genome-wide association study (GWAS) for 13 reproductive traits
measured on 205 F2 boars at day 300 using 60 K single nucleotide polymorphism
(SNP) data imputed from a reference panel of 1200 pigs in a White Duroc *
Erhualian F2 intercross population. We identified 10 significant loci for seven
traits on eight pig chromosomes (SSC). Two loci surpassed the genome-wide
significance level, including one for epididymal weight around 60.25 Mb on SSC7
and one for semen temperature around 43.69 Mb on SSC4. Four of the 10 significant
loci that we identified were consistent with previously reported quantitative
trait loci for boar reproduction traits. We highlighted several interesting
candidate genes at these loci, including APN, TEP1, PARP2, SPINK1 and PDE1C. To
evaluate the imputation accuracy, we further genotyped nine GWAS top SNPs using
PCR restriction fragment length polymorphism or Sanger sequencing. We found an
average of 91.44% of genotype concordance, 95.36% of allelic concordance and 0.85
of r(2) correlation between imputed and real genotype data. This indicates that
our GWAS mapping results based on imputed SNP data are reliable, providing
insights into the genetic basis of boar reproductive traits.
PMID- 26425934
TI - Are Cellulose Nanofibers a Solution for a More Circular Economy of Paper
Products?
AB - This paper presents the study of the feasibility of incorporating lignocellulosic
nanofibers (LCNF) to paper in order to maintain the relevant physical properties
and increase the number of cycles that paper can be recycled in the technosphere
in a more circular economy. For that purpose, the effect of mechanical refining
in recycling processes was compared with that of the novel LCNF addition. In this
sense, the behavior of a bleached kraft hardwood pulp when recycled was
investigated, as well as the effects of each methodology. Since there are many
issues to be considered when trying to replace a technology, the present paper
analyses its feasibility from a technical and environmental point of view.
Technically, LCNF present greater advantages against mechanical refining, such as
higher mechanical properties and longer durability of the fibers. A preliminary
life cycle assessment showed that the environmental impacts of both systems are
very similar; however, changing the boundary conditions to some feasible future
scenarios, led to demonstrate that the CNF technology may improve significantly
those impacts.
PMID- 26425935
TI - Oral Anticoagulation and the Risk of Stroke or Death in Patients With Atrial
Fibrillation and One Additional Stroke Risk Factor: The Loire Valley Atrial
Fibrillation Project.
AB - BACKGROUND: It remains uncertain whether patients with atrial fibrillation (AF)
and a single additional stroke risk factor (congestive heart failure,
hypertension, age >= 75 years, diabetes mellitus, prior stroke or
thromboembolism, vascular disease, age 65-74 years, and sex category [CHA2DS2
VASc] score = 1 in men, 2 in women) should be treated with oral anticoagulation
(OAC). We investigated the risk of ischemic stroke, systemic embolism, and death
in a community-based cohort of unselected patients with AF with zero to one
stroke risk factor based on the CHA2DS2-VASc score. METHODS: Among 8,962 patients
with AF seen between 2000 and 2010, 2,177 (24%) had zero or one additional stroke
risk factor, of which 53% were prescribed OAC. RESULTS: Over a follow-up of 979
+/- 1,158 days, 151 (7%) had a major adverse event (stroke/systemic
thromboembolism/death). Prescription of OAC was not associated with a better
prognosis for stroke/systemic thromboembolism/death for patients in the "low
risk" category (ie, CHA2DS2-VASc score = 0 for men or 1 for women; adjusted
hazard ratio [HR], 0.68; 95% CI, 0.35-1.31; P = .25). OAC use was independently
associated with a better prognosis in patients with AF with a single additional
stroke risk factor (ie, CHA2DS2-VASc score = 1 in men, 2 in women; adjusted HR,
0.59; 95% CI, 0.40-0.86; P = .007). CONCLUSIONS: Among patients with AF with a
single additional stroke risk factor (CHA2DS2-VASc score = 1 in men, 2 in women),
OAC use was associated with an improved prognosis for stroke/systemic
thromboembolism/death.
PMID- 26425936
TI - Sensitive Detection of Deliquescent Bacterial Capsules through Nanomechanical
Analysis.
AB - Encapsulated bacteria usually exhibit strong resistance to a wide range of
sterilization methods, and are often virulent. Early detection of encapsulation
can be crucial in microbial pathology. This work demonstrates a fast and
sensitive method for the detection of encapsulated bacterial cells.
Nanoindentation force measurements were used to confirm the presence of
deliquescent bacterial capsules surrounding bacterial cells. Force/distance
approach curves contained characteristic linear-nonlinear-linear domains,
indicating cocompression of the capsular layer and cell, indentation of the
capsule, and compression of the cell alone. This is a sensitive method for the
detection and verification of the encapsulation status of bacterial cells. Given
that this method was successful in detecting the nanomechanical properties of two
different layers of cell material, i.e. distinguishing between the capsule and
the remainder of the cell, further development may potentially lead to the
ability to analyze even thinner cellular layers, e.g. lipid bilayers.
PMID- 26425938
TI - Self-organization of "fibro-axonal" composite tissue around unmodified metallic
micro-electrodes can form a functioning interface with a peripheral nerve: A new
direction for creating long-term neural interfaces.
AB - INTRODUCTION: A long-term peripheral neural interface is an area of intense
research. The use of electrode interfaces is limited by the biological response
to the electrode material. METHODS: We created an electrode construct to harbor
the rat sciatic nerve with interposition of autogenous adipose tissue between the
nerve and the electrode. The construct was implanted for 10 weeks. RESULTS:
Immunohistochemistry showed a unique laminar pattern of axonal growth layered
between fibro-collagenous tissue, forming a physical interface with the tungsten
micro-electrode. Action potentials transmitted across the intrerface showed mean
conduction velocities varying between 6.99 +/- 2.46 and 20.14 +/- 4 m/s.
CONCLUSIONS: We have demonstrated the feasibility of a novel peripheral nerve
interface through modulation of normal biologic phenomena. It has potential
applications as a chronic implantable neural interface.
PMID- 26425939
TI - The effect of ferrous-chelating hairtail peptides on iron deficiency and
intestinal flora in rats.
AB - BACKGROUND: Chelating agents, such as small peptides, can decrease free iron
content and increase iron bioavailability. They may have promising therapeutic
potential and may prevent the pro-oxidant effects of low molecular weight iron.
Hairtail is a species of fish that is rich in easily digestible proteins. We
extended this strategy for iron delivery by using an enzymatic hydrolysate of
hairtail as the chelating agent and found that the ferrous-chelating hairtail
peptides have anti-anaemic activity in Sprague-Dawley rats with anaemia. RESULTS:
The anti-anaemic activity of ferrous-chelating hairtail peptides prepared by
enzymatic hydrolysis of the hairtail and ferrous chelation was studied in rat
models of iron deficiency anaemia. After the end of the 35 d experiment, we noted
significant differences in haemoglobin, mean corpuscular volume, haemoglobin
distribution width, and ferritin concentrations between those animals
supplemented with ferrous-chelating hairtail peptides and FeSO4 and healthy
animals. There were no negative side effects on the animals' growth or behaviour.
There was no obvious inflammation in the intestinal mucosa lamina propria and no
unbalance of intestinal flora. CONCLUSION: The novel ferrous-chelating hairtail
peptides may be a suitable fortificant for improving iron-deficiency status. Our
findings demonstrated that this multi-tracer technique has many applications in
nutritional research. (c) 2015 Society of Chemical Industry.
PMID- 26425937
TI - Structures and Energetics of Four Adjacent G.U Pairs That Stabilize an RNA Helix.
AB - Consecutive G.U base pairs inside RNA helices can be destabilizing, while those
at the ends of helices are thermodynamically stabilizing. To determine if this
paradox could be explained by differences in base stacking, we determined the
high-resolution (1.32 A) crystal structure of (5'-GGUGGCUGUU-3')2 and studied
three sequences with four consecutive terminal G.U pairs by NMR spectroscopy. In
the crystal structure of (5'-GGUGGCUGUU-3')2, the helix is overwound but retains
the overall features of A-form RNA. The penultimate base steps at each end of the
helix have high base overlap and contribute to the unexpectedly favorable
energetic contribution for the 5'-GU-3'/3'-UG-5' motif in this helix position.
The balance of base stacking and helical twist contributes to the positional
dependence of G.U pair stabilities. The energetic stabilities and similarity to A
form RNA helices suggest that consecutive G.U pairs would be recognized by RNA
helix binding proteins, such as Dicer and Ago. Thus, these results will aid
future searches for target sites of small RNAs in gene regulation.
PMID- 26425940
TI - Differences in major bacterial populations in the intestines of mature broilers
after feeding virginiamycin or bacitracin methylene disalicylate.
AB - AIMS: The purpose of this study was to compare the effects of feeding
virginiamycin or bacitracin methylene disalicylate (BMD), two in-feed antibiotics
typically used by commercial poultry producers in the United States, on the
chicken gastrointestinal microbiota. METHODS AND RESULTS: 454 pyrosequencing of
the V6-V8 region of the 16S rRNA gene and quantitative PCR were employed to
examine the bacterial microbiota and Clostridium perfringens, respectively, in
the jejunum and caecum of market-age broiler chickens over four replicate grow
outs. CONCLUSIONS: Our results suggest that virginiamycin has a more pronounced
impact on broiler gastrointestinal tract bacterial communities, relative to BMD,
manifested primarily through significant enrichments in the genus
Faecalibacterium in the caecum and a distinct population of Lactobacillus,
OTU_02, in both the jejunum and caecum. No evidence for a difference among the
diets in Cl. perfringens levels in the jejunum or caecum was observed.
SIGNIFICANCE AND IMPACT OF THE STUDY: This work represents the highest resolution
comparison to date of the jejunum and caecum microbiota in broilers fed either
virginiamycin or BMD, and provides evidence for specific bacterial OTUs
potentially involved in the health and performance benefits typically attributed
to these in-feed antibiotics.
PMID- 26425941
TI - Can Low-Cost Strategies Improve Attendance Rates in Brief Psychological Therapy?
Double-Blind Randomized Controlled Trial.
AB - OBJECTIVES: To assess if telephone text message appointment reminders and
orientation leaflets can increase the proportion of patients who attend brief
interventions after being assessed as suitable for guided self-help following
cognitive behavioral therapy principles. METHOD: Attendance was operationally
defined as having accessed at least 1 therapy appointment. A secondary outcome
was the proportion of attenders who completed or dropped out of therapy. After
initial assessment, 254 patients with depression and anxiety disorders were
randomly assigned to 1 of 3 groups: (a) usual waitlist control, (b) leaflet, (c)
leaflet plus text message. Differences in the proportions of patients who started
and completed therapy across groups were assessed using chi-square and logistic
regression analyses. RESULTS: Overall, 63% of patients in this sample attended
therapy. Between-group differences were not significant for attendance, x(2) (2)
= 3.94, p = .14, or completion rates, x(2) (2) = 2.98, p = .23. These results
were not confounded by demographic or clinical characteristics. CONCLUSIONS: Low
cost strategies appear to make no significant difference to therapy attendance
and completion rates.
PMID- 26425942
TI - Individual and combined effects of deoxynivalenol and alpha-zearalenol on cell
proliferation and steroidogenesis of granulosa cells in cattle.
AB - This study was conducted to evaluate the impact of deoxynivalenol (DON) and
zearalenone (ZEA) metabolite, alpha-zearalenol (alpha-Zol), on cell proliferation
and steroidogenesis of bovine large (LG) follicle granulosa cells (GC). LGGC were
obtained from bovine ovarian follicles (8-22 mm) and were cultured for 2 days in
medium containing 10% fetal bovine serum followed by 1 or 2 days in serum-free
medium without (control) or with treatments. Three different experiments were
performed using different dosages of DON and alpha-Zol and in different
combinations and a fourth experiment evaluated estradiol effects on granulosa
cell proliferation. DON inhibited progesterone (P4) and estradiol (E2) production
at high dose. alpha-Zol alone and in combination with DON increased cell growth.
Estradiol inhibited cell growth indicating alpha-Zol is not acting as an estrogen
agonist. This study demonstrates that alpha-Zol and DON can impact in vitro GC
function, however further studies will be required to better understand the
mechanism of action and reproductive effects of Fusarium mycotoxins.
PMID- 26425943
TI - Toxicological effects of silver nanoparticles.
AB - Nanotechnology offers numerous biomedical applications and in so doing, exerts
toxic effects. AgNPs, one of the metallic nanoparticles is known for its
antibacterial applications and hence exposed to human through various healthcare
products. Analysis of its toxic effects is necessary before its appliance into
the biomedical field. Hence, this mini-review focuses on toxic effects of AgNPs
related to human and his environment in vitro and in vivo.
PMID- 26425944
TI - Frog-Leg Test Maneuver for the Diagnosis of Injuries to the Posterolateral Corner
of the Knee: A Diagnostic Accuracy Study.
AB - OBJECTIVE: To determine the sensitivity and specificity of a new clinical test
for the diagnosis of injuries to the posterolateral corner of the knee by using
magnetic resonance imaging (MRI) as the reference standard. DESIGN: Diagnostic
accuracy study. SETTING: A tertiary care teaching hospital. PARTICIPANTS: Twelve
subjects with chronic instability of the knee and posterolateral corner injury
diagnosed by intraoperative findings and 9 subjects without posterolateral corner
injury (used as controls). INTERVENTIONS: Injured and uninjured knees were
assessed blindly by 2 examiners using a new clinical diagnostic test (the frog
leg test) and the classic varus stress test. MAIN OUTCOME MEASURES: Injuries to
the posterolateral corner of the knee identified by the 2 clinical tests.
Findings were compared and examined for reproducibility, and kappa statistic was
used to assess interobserver agreement. Test results were compared with those of
MRI and intraoperative findings to determine diagnostic accuracy. RESULTS: The
frog-leg test showed high interobserver agreement (kappa, 0.86), with a high rate
(83%-100%) of agreement with the intraoperative diagnosis. The frog-leg test had
high sensitivity (91.7%) and specificity (94.5%) for detecting posterolateral
corner injuries. The sensitivity of the varus stress test increased from 83.3% to
90.0% when combined with the frog-leg test. CONCLUSIONS: Examiners were able to
identify posterolateral corner injuries and differentiate injured from uninjured
knees using the frog-leg test, which could potentially be used as an ancillary
tool to the varus stress test in diagnosing injuries to the posterolateral corner
of the knee. Larger studies are needed to confirm our findings.
PMID- 26425954
TI - Category Index.
PMID- 26425958
TI - Continuing Medical Education and Disclosures.
PMID- 26425956
TI - Meeting-at-a-Glance.
PMID- 26425959
TI - Poster Sessions.
PMID- 26425962
TI - Organic Single-Crystal Semiconductor Films on a Millimeter Domain Scale.
AB - Nucleation and growth processes can be effectively controlled in organic
semiconductor films through a new concept of template-mediated molecular crystal
seeds during the phase transition; the effective control of these processes
ensures millimeter-scale crystal domains, as well as the performance of the
resulting organic films with intrinsic hole mobility of 18 cm(2) V(-1) s(-1).
PMID- 26425963
TI - Generation of Hydrogen by Visible Light-Induced Water Splitting with the Use of
Semiconductors and Dyes.
AB - Photosynthesis that occurs in plants involves both the oxidation of water and the
reduction of carbon dioxide. Plants carry out these reactions with ease, by
involving electron-transport chains. In this article, hydrogen generation by the
reduction of water in the laboratory by using semiconductor nanostructures
through artificial photosynthesis is examined. Dye-sensitized photochemical
generation of hydrogen from water is also discussed. Hydrogen generation by these
means has great technological relevance, since it is an environmentally friendly
fuel. The way in which oxygen can be generated by the oxidation of water using
metal oxide catalysts is also shown.
PMID- 26425961
TI - Relationships Between Measures of the Ability to Perform Vision-Related
Activities, Vision-Related Quality of Life, and Clinical Findings in Patients
With Glaucoma.
AB - IMPORTANCE: To our knowledge, few studies have combined an objective measure of
vision-related performance (VRP) and subjective measures of vision-related
quality of life (VRQoL) with clinically related visual parameters, particularly
in a large, prospective, cohort study setting. OBJECTIVE: To examine the
relationships between clinical visual assessments and both a VRP and 2 self
reported VRQoL measurements. DESIGN, SETTING, AND PARTICIPANTS: Patients (N =
161) with moderate-stage glaucoma recruited from the Glaucoma Service at Wills
Eye Hospital, Philadelphia, Pennsylvania, were enrolled from May 2012 to May 2014
in an ongoing prospective, 4-year longitudinal observational study. This report
includes cross-sectional results from the baseline visit. Patients received a
complete ocular examination, automated visual field (VF) test and Cirrus optical
coherence tomographic scan. Contrast sensitivity was measured with the Pelli
Robson and the Spaeth-Richman Contrast Sensitivity (SPARCS) tests. Vision-related
performance was assessed by the Compressed Assessment of Ability Related to
Vision (CAARV) test. Vision-related QoL was assessed by the National Eye
Institute Visual Function Questionnaire 25 (NEI-VFQ-25) and a modified Glaucoma
Symptom Scale (MGSS). MAIN OUTCOMES AND MEASURES: Correlations between clinical
measures and CAARV, NEI-VFQ-25, and MGSS scores. RESULTS: A total of 161 patients
were enrolled in the study. The strongest correlation was found between SPARCS
score in the better eye and total CAARV score (r = 0.398; 95% CI, 0.235-0.537; P
< .001). The CAARV score also correlated with the Pelli-Robson score (r = 0.353;
95% CI, 0.186-0.499; P = .001), VF mean deviation (r = 0.366; 95% CI, 0.200
0.510; P < .001), and VA (r = -0.326, 95% CI = -0.476 to -0.157; P = .003) in the
better eye. There were more statistically significant correlations between
contrast sensitivity tests and VF mean deviation with VRQoL measurements than
with other clinical measures (visual acuity, intraocular pressure, Disc Damage
Likelihood Scale, and mean retinal nerve fiber layer thickness). The MGSS scores
were lower (worse) in women compared with men (P = .03 for binocular, P = .01 for
better eye, and P = .05 for the worse eye). Structural measures (eg, Disc Damage
Likelihood Scale, and retinal nerve fiber layer thickness) were generally not
informative with respect to VRP or VRQoL. CONCLUSIONS AND RELEVANCE: Contrast
sensitivity tests and VF mean deviation were associated with both objective
measures of the ability to act and subjective measurements of VRQoL. The
strongest correlation was between SPARCS score (contrast sensitivity) in the
better eye and total CAARV score. Therefore, measurement of contrast sensitivity
should be considered when evaluating patients' VRQoL. The results of this study
were limited by the patient population and apply only within the bounds of the
tested cohort.
PMID- 26425964
TI - The triplet-charge annihilation in copolymer-based organic light emitting diodes:
through the "Scattering Channel" or the "Dissociation Channel"?
AB - In organic semiconductors, the triplet-charge annihilation (TCA) is one of the
most common excitonic interactions influencing the opto-electronic power
conversion efficiency of the devices. However, it is still unclear whether the
TCA reaction goes through the "Scattering Channel" or the "Dissociation Channel".
In this work, by measuring the organic magneto-current (OMC) of the conjugated co
polymer poly[{9,9-dioctyl-2,7-divinylene-fluorenylene}-alt-co-{2-methoxy-5-(2
ethylhexyloxy)-1,4-phenyene}] (PFOPV)-based organic light-emitting diodes (OLEDs)
containing both localized exciton (LE) and charge-transfer-complex (CT), it is
found that (3)LE and (3)CT play a crucial role in the "Scattering Channel" and
the "Dissociation Channel" of TCA, respectively. This argument was supported by
the simulations of Lorentzian and non-Lorentzian functions used, respectively,
for intersystem crossing (or reverse intersystem crossing, RISC) and TCA effects.
Moreover, by inserting a tris(2,4,6-trimethyl-3-(pyridin-3-yl)phenyl)borane
(3TPYMB) layer between PFOPV and the cathode, we improved the electroluminescence
efficiency of PFOPV-based OLEDs by suppressing the TCA when (3)CT involves in
RISC. Our results give insights into the spin-dependent TCA limiting the
efficiency of hotly discussed CT-based OLEDs.
PMID- 26425966
TI - Classical Amphiphilic Behavior of Nonclassical Amphiphiles: A Comparison of
Metallacarborane Self-Assembly with SDS Micellization.
AB - The self-assembly of metallacarboranes, a peculiar family of compounds exhibiting
surface activity and resembling molecular-scale Pickering stabilizers, has been
investigated by comparison to the micellization of sodium dodecylsulfate (SDS).
These studies have shown that molecules without classical amphiphilic topology
but with an inherent amphiphilic nature can behave similarly to classical
surfactants. As shown by NMR techniques, the self-assembly of both
metallacarboranes and SDS obey a closed association model. However, the
aggregation of metallacarboranes is found to be enthalpy-driven, which is very
unusual for classical surfactants. Possible explanations of this fact are
outlined.
PMID- 26425965
TI - Simulation of biological therapies for degenerated intervertebral discs.
AB - The efficacy of biological therapies on intervertebral disc repair was
quantitatively studied using a three-dimensional finite element model based on a
cell-activity coupled multiphasic mixture theory. In this model, cell metabolism
and matrix synthesis and degradation were considered. Three types of biological
therapies-increasing the cell density (Case I), increasing the glycosaminoglycan
(GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case
III)-to the nucleus pulposus (NP) of each of two degenerated discs [one mildly
degenerated (e.g., 80% viable cells in the NP) and one severely degenerated
(e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without
treatment were also simulated as a control. The cell number needed, nutrition
level demanded, time required for the repair, and the long-term outcomes of these
therapies were analyzed. For Case I, the repair process was predicted to be
dependent on the cell density implanted and the nutrition level at disc
boundaries. With sufficient nutrition supply, this method was predicted to be
effective for treating both mildly and severely degenerated discs. For Case II,
the therapy was predicted to be effective for repairing the mildly degenerated
disc, but not for the severely degenerated disc. Similar results were predicted
for Case III. No change in cell density for Cases II and III were predicted under
normal nutrition level. This study provides a quantitative guide for choosing
proper strategies of biological therapies for different degenerated discs.
PMID- 26425968
TI - Disruptive Innovation: Latest Buzzword or New Reality?
AB - This is an inaugural department column focusing on disruptive healthcare
innovations and the implications for nurse leaders and nursing practice.
PMID- 26425967
TI - Certification as a Quality Initiative.
AB - The vice president of the Certification and Measurement Services for the American
Nurses Credentialing Center presents this month's column focused on the value of
certification for both the patient and the organization.
PMID- 26425969
TI - Creating Supportive Environments and Thriving in a Volatile, Uncertain, Complex,
and Ambiguous World.
AB - Nurse executives (NEs) are operating in a volatile, uncertain, complex, and
ambiguous world. NEs must create supportive environments that promote staff
empowerment, resilience, and alignment, to ensure organizational success. In
addition, NEs need to be transparent and create a culture of partnership with
their staff. The ability of NEs to create and sustain this environment is vital
in supporting teams to successfully navigate in today's healthcare environment.
PMID- 26425970
TI - Findings From the 2015 National Forum of State Nursing Workforce Centers Annual
Meeting.
AB - Estimating the future nursing workforce needs is critical to all aspects of
nursing care. Currently, the healthcare system is undergoing chaotic change, and
predicting the workforce needs over the next 10 years has been challenging. The
efforts of Dr Peter Buerhaus and his associates in addressing nursing workforce
issues over the last 25 years are a hallmark. Dr Buerhaus joined forces with the
state nursing workforce centers to discuss new approaches to this critical issue.
PMID- 26425971
TI - US Nurses' Perceptions Regarding Caring for Suspected, Probable, and Confirmed
Ebola Virus Disease Patients, Part 1: A Quantitative Analysis.
AB - OBJECTIVE: This study examined US hospital, ambulatory/outpatient facility, and
clinic nurses' perceptions regarding care of persons under investigation (PUIs)
and confirmed Ebola virus disease (EVD) patients and EVD nursing workforce
impact. BACKGROUND: Timely research was warranted to better understand nurses'
perceptions. METHODS: This survey research used convenience sampling of RNs,
LPNs, and nurse technicians. Respondents completed a 45-item electronic validated
survey. RESULTS: Overall average perceived risk with providing care was higher
for confirmed EVD patients (5.2) than PUIs (4.8) (0 = no risk, 10 = highest
risk). Few had cared for confirmed EVD patients (0.3%) or PUIs (0.7%). Whereas
48.4% felt prepared in protecting themselves from contracting EVD, 25.2% were
concerned with contracting EVD. More nurses (45.9%) felt they should be able to
opt out of caring for confirmed EVD patients as compared with those caring for
PUIs (39.2%). EVD emergence had not affected (85.8%) nurses' willingness to
provide direct patient care; however, 6.8% reported EVD has decreased years
planned in the nursing workforce. CONCLUSIONS: Nurses reported moderate risk for
EVD-related patient care; 6.8% may leave the workforce earlier.
PMID- 26425972
TI - Models of Discharge Care in Magnet(r) Hospitals.
AB - OBJECTIVE: The aim of this article is to describe how the discharge preparation
process is operationalized in Magnet(r) hospitals. BACKGROUND: Nationally, there
are intensive efforts toward improving discharge transitions and reducing
readmissions. Discharge preparation is a core hospital function, yet there are
few reports of operational models. METHODS: This was a descriptive, Web-based
survey of 32 Magnet hospitals (64 units) participating in the Readiness
Evaluation and Discharge Interventions study. RESULTS: Most hospitals have
adopted 1 or more national readmission reduction initiatives. Most unit models
include several discharge preparation roles; RN case managers, and discharging
RNs lead the process. Nearly one-half of units actively screen for readmission
risk. More than three-fourths report daily discharge rounds, but less than one
third include the patient and family. More than two-thirds report a follow-up
phone call, mostly to assess patient satisfaction. CONCLUSIONS: Magnet hospitals
operationalize discharge preparation differently. Recommended practices from
national discharge initiatives are inconsistently used. RNs play a central role
in discharge planning, coordination, and teaching.
PMID- 26425973
TI - A Phenomenological Study of Nurse Manager Interventions Related to Workplace
Bullying.
AB - OBJECTIVE: The aim of this study was to acquire nurse managers' perspectives as
to the scope of workplace bullying, which interventions were deemed as effective
and ineffective, and what environmental characteristics cultivated a healthy,
caring work environment. BACKGROUND: Research has linked workplace bullying among
RNs to medical errors, unsafe hospital environments, and negative patient
outcomes. Limited research had been conducted with nurse managers to discern
their perspectives. METHODS: Six nurse managers from hospital settings
participated in in-depth, semistructured interviews. Ray's theory of bureaucratic
caring guided the study. RESULTS: These themes emerged: (a) awareness, (b) scope
of the problem, (c) quality of performance, and (d) healthy, caring environment.
Findings indicated mandated antibullying programs were not as effective as
individual manager interventions. CONCLUSIONS: Systems must be in place to hold
individuals accountable for their behavior. Communication, collective support,
and teamwork are essential to create environments that lead to the delivery of
safe, optimum patient care.
PMID- 26425974
TI - Major Predictors of Inpatient Falls: A Multisite Study.
AB - OBJECTIVE: The purpose of this secondary data analysis was to identify key
factors predictive of falls in hospitals. BACKGROUND: Patient falls remain a
major concern for hospitals. Falls can increase patient morbidity/mortality and
increase legal risk/cost for institutions. While a number of high-risk falls
assessments are available, key predictors of falls have not been identified.
METHODS: A secondary data analysis was performed on 281,865 high-risk falls
assessments collected in a multisite study. RESULTS: For the total sample,
logistic regression analyses demonstrated that 3 factors, falls within the past 6
months (OR=2.98), confusion (odds ratio, 2.05), taking a laxative (odds ratio,
1.54), are strong predictors of falling. Similar results were found for
individual hospitals, different units within hospitals, and urban versus rural
hospital locations. CONCLUSION: Findings suggest that assessments of fall risk
should heavily weigh the 3 predictors identified in this study. Another approach
would be to intervene based on these predictors.
PMID- 26425975
TI - Interactive Care Model: A Framework for More Fully Engaging People in Their
Healthcare.
AB - Transformation of care delivery requires rethinking the relationship between the
person and clinician. The model described provides a process to more fully engage
patients in their care. Five encounters include assessing capacity for
engagement, exchanging information and choices, planning, determining
interventions, and evaluating the effectiveness of engagement interventions.
Created by researchers and validated by experts, implications for practice,
education, and policy are explored.
PMID- 26425976
TI - Simulation-Based Mastery Learning Improves Central Line Maintenance Skills of ICU
Nurses.
AB - OBJECTIVE: This study evaluated the impact of a simulation-based mastery learning
(SBML) curriculum on central line maintenance and care among a group of ICU
nurses. METHODS: The intervention included 5 tasks: (a) medication
administration, (b) injection cap (needleless connector) changes, (c) tubing
changes, (d) blood drawing, and (e) dressing changes. All participants underwent
a pretest, engaged in deliberate practice with directed feedback, and completed a
posttest. We compared pretest and posttest scores and assessed correlations
between demographics, self-confidence, and pretest performance. RESULTS: The
number of nurses passing each task at pretest varied from 24 of 49 (49%) for
dressing changes to 44 of 49 (90%) for tubing changes. At pretest, scores ranged
from a median of 0.0% to 73.1%. At posttest, all scores rose to a median of
100.0%. Total years in nursing and ICU nursing had significant, negative
correlations with medication administration pretest performance (r = -0.42, P =
.003; r = -0.42, P = .003, respectively). CONCLUSION: ICU nurses displayed large
variability in their ability to perform central line maintenance tasks. After
SBML, there was significant improvement, and all nurses reached a predetermined
level of competency.
PMID- 26425977
TI - Design and Outcome of a Certification Preparation Program for Outpatient Nurses.
AB - This article presents the design, implementation, and outcomes of a certification
preparation program for nurses working in an outpatient clinic. A nurse educator
designed curriculum using the Certified Breast Care Nurse test blueprint. Nurse
administrators provided the resources and the staff coverage to allow all staff
members to attend the sessions without disruption to patient care. This
outpatient center has achieved and sustained 100% certification among eligible
nurses over the past 5 years.
PMID- 26425978
TI - Stability and toxicity of tris-tolyl bismuth(V) dicarboxylates and their
biological activity towards Leishmania major.
AB - A series of 29 tris-tolyl bismuth(v) di-carboxylato complexes of composition
[Bi(Tol)3(O2CR)2] involving either ortho, meta or para substituted tolyl ligands
have been synthesized and characterised. Of these 15 were assessed for their
toxicity towards Leishmania promastigotes and human fibroblast cells, with ten
then being subsequently assessed against parasite amastigotes. The carboxylate
ligands are drawn from a series of substituted and biologically relevant benzoic
acids which allow a comparison with earlier studies on [BiPh3(O2CR)2] and
analogous Sb(v) [SbAr3(O2CR)2] (Ar = Ph and Tol) complexes. Twelve complexes have
been structurally characterized by single crystal X-ray diffraction and shown to
adopt a typical trigonal bipyramidal geometry in which the three tolyl ligands
occupy the equatorial plane. NMR studies on two illustrative examples indicate
that the complexes are stable in D2O and DMSO but only have a half-life of 1.2
hours in culture medium, with glucose being a contributing factor in
decomposition and reduction to Bi(Tol)3. Despite their short lifetime many
complexes show significant toxicity towards promastigotes at low concentration
(<6 MUM) and at that concentration provide for good selectivity indices (parasite
vs. mammalian cells), for example 114 for [Bi(o-Tol)3(O2CC6H3(2-OH,5-C6H3(2,4
F2)))2] and 838 for [Bi(m-Tol)3(O2CC6H4(2-OAc))2]. Best activity and selectivity
is observed with complexes containing o- and m-tolyl ligands, and it appears the
primary influence on fibroblast toxicity is the Ar ligand while the carboxylate
influences promastigote toxicity. The complexes are less effective in vitro
against the parasite amastigotes, where longer incubation times and harsher
chemical and biological environments are encountered in the assay. Nevertheless,
there were some statistically relevant differences at 1 MUM against the positive
controls with the best performing complexes being [Bi(o-Tol)3(O2CC6H4(2-EtO))2]
and [Bi(m-Tol)3(O2CC6H4(2-OAc))2].
PMID- 26425979
TI - The effect of pressure on cation-cellulose interactions in cellulose/ionic liquid
mixtures.
AB - Cation-cellulose interactions in binary mixtures of [EMIM][OAc] and cellulose
have been investigated using high-pressure infrared spectroscopy. At low
concentrations of cellulose, almost no changes were observed in the imidazolium
C(2)-H frequency; on the other hand, at high concentrations of cellulose,
increases in the C(2)-H vibration frequency were observed under ambient pressure.
As the pressure was elevated, the imidazolium C(2)-H absorption of the
[EMIM][OAc]/cellulose mixtures underwent band-narrowing and blue-shifts in the
frequency. These observations suggest that high pressures may strengthen the
hydrogen bonds formed between C(2)-H and cellulose, possibly forcing the
cellulose to dissociate clusters of ionic liquid through enhanced cation
cellulose interactions. In contrast to the cation-cellulose interaction results,
the COO(-) absorption of the anion does not show dramatic changes under high
pressures. Our results indicate the possibility of enhanced cation-cellulose
interactions through pressure elevation, demonstrating that high pressures may
have the potential to tune the relative contributions of cation-cellulose and
anion-cellulose interactions in cellulose/ionic liquid mixtures.
PMID- 26425980
TI - ORS Interview with Warren Snell.
PMID- 26425981
TI - Proposal for a Simple and Efficient Monthly Quality Management Program Assessing
the Consistency of Robotic Image-Guided Small Animal Radiation Systems.
AB - Modern pre-clinical radiation therapy (RT) research requires high precision and
accurate dosimetry to facilitate the translation of research findings into
clinical practice. Several systems are available that provide precise delivery
and on-board imaging capabilities, highlighting the need for a quality management
program (QMP) to ensure consistent and accurate radiation dose delivery. An
ongoing, simple, and efficient QMP for image-guided robotic small animal
irradiators used in pre-clinical RT research is described. Protocols were
developed and implemented to assess the dose output constancy (based on the AAPM
TG-61 protocol), cone-beam computed tomography (CBCT) image quality and object
representation accuracy (using a custom-designed imaging phantom), CBCT-guided
target localization accuracy and consistency of the CBCT-based dose calculation.
To facilitate an efficient read-out and limit the user dependence of the QMP data
analysis, a semi-automatic image analysis and data representation program was
developed using the technical computing software MATLAB. The results of the first
6-mo experience using the suggested QMP for a Small Animal Radiation Research
Platform (SARRP) are presented, with data collected on a bi-monthly basis. The
dosimetric output constancy was established to be within +/-1 %, the consistency
of the image resolution was within +/-0.2 mm, the accuracy of CBCT-guided target
localization was within +/-0.5 mm, and dose calculation consistency was within +/
2 s (+/-3%) per treatment beam. Based on these results, this simple quality
assurance program allows for the detection of inconsistencies in dosimetric or
imaging parameters that are beyond the acceptable variability for a reliable and
accurate pre-clinical RT system, on a monthly or bi-monthly basis.
PMID- 26425982
TI - Technical Assessment of Internal Surface Smoothness and Particle Transmission to
the American National Standard ANSI/HPS N13.1-2011.
AB - Clause 6.4.4 in the American National Standard ANSI/HPS N13.1 standard "Sampling
and Monitoring Releases of Airborne Radioactive Substances From the Stacks and
Ducts of Nuclear Facilities" addresses the internal smoothness of sample
transport lines present between the nozzle and the analyzer (or collector). The
appropriateness of this clause is evaluated by comparing roughness length of
various materials against the required relative roughness and by conducting
computational fluid dynamic modeling. The results indicate that the inclusion of
numerical criteria for the relative roughness of pipe by the ANSI/HPS N13.1-2011
(clause 6.4.4) is not appropriate. Recommended alternatives would be elimination
of the numerical criteria or modification of the standard to include a variable
criterion for relative roughness.
PMID- 26425983
TI - Attenuation of X and Gamma Rays in Personal Radiation Shielding Protective
Clothing.
AB - A collection of personal radiation shielding protective clothing, suitable for
use in case of accidents in nuclear facilities or radiological emergency
situations involving radioactive agents, was gathered and tested at the Nuclear
Protection Department of the National Institute for Nuclear, Chemical and
Biological Protection, Czech Republic. Attenuating qualities of shielding layers
in individual protective clothing were tested via spectra measurement of x and
gamma rays, penetrating them. The rays originated from different radionuclide
point sources, the gamma ray energies of which cover a broad energy range. The
spectra were measured by handheld spectrometers, both scintillation and High
Purity Germanium. Different narrow beam geometries were adjusted using a special
testing bench and a set of various collimators. The main experimentally
determined quantity for individual samples of personal radiation shielding
protective clothing was x and gamma rays attenuation for significant energies of
the spectra. The attenuation was assessed comparing net peak areas (after
background subtraction) in spectra, where a tested sample was placed between the
source and the detector, and corresponding net peak areas in spectra, measured
without the sample. Mass attenuation coefficients, which describe attenuating
qualities of shielding layers materials in individual samples, together with
corresponding lead equivalents, were determined as well. Experimentally assessed
mass attenuation coefficients of the samples were compared to the referred ones
for individual heavy metals.
PMID- 26425984
TI - Lessons Learned on the Presentation of Scan Data.
AB - Technicians performed a radiological survey of a surplus metal tank to support
disposition planning at an Oak Ridge, TN, site. The survey included radiation
scans to identify contamination and, if identified, define the boundary and
magnitude of contamination. Fixed-point 1-min measurements were also collected at
randomly selected locations for comparison against the site's free release limit
of 5,000 disintegrations per minute per 100 cm (dpm 100 cm) (0.83 Bq cm). Scan
data were recorded using a data logger as a means to document surveyor
observation-logged data captured at 1-s intervals and converted to counts per
minute (cpm) by the data logger software were presented in the project report.
Both the qualitative scan data (in cpm) and the quantitative direct measurements
(in dpm 100 cm) were reported for completeness, so stakeholders had all available
information to support disposition decisions. However, a new stakeholder
introduced to the project at the reporting phase of work-used the instrument
efficiency and background data to convert the scan data from cpm to dpm 100 cm,
then compared the converted results to the site limit. Many of the converted
values exceeded 5,000 dpm 100 cm. This resulted in delays in tank disposition and
additional project costs that could have been avoided if the proper use and
interpretation of scan data and implications of radon progeny buildup on oxidized
metal surfaces had been better communicated.
PMID- 26425985
TI - Occupational Exposure to Veterinary Workers from the Positron Emission Tomography
Imaging Agent 64Cu-ATSM.
AB - Cu-ATSM is an emerging radiopharmaceutical for diagnostic use in positron
emission tomography (PET), but to date there are no studies that assess the
potential occupational doses to workers in either human or veterinary medicine.
This study was aimed at determining the external radiation dose to veterinary
workers from clinical PET/CT (PET combined with computed tomography) procedures
using Cu-ATSM. To determine the dose to the workers, each worker was assigned two
Electronic Personal Dosimeters (EPDs) to be worn on the chest and waist during
the entirety of each procedure. The workers monitored during this study included
a radiobiologist, a nuclear medicine technologist, an anesthesiologist, and a
veterinary surgeon. Seven canine patients were imaged with an average mass of
33.7 kg (a range of 20.0-55.1 kg) with an average injected activity of 5 MBq kg.
The dose range for the radiobiologist was 2-17 MUSv (mean of 7.1 MUSv), for the
nuclear medicine technologist 0-14 MUSv (mean of 5.6 MUSv), for the
anesthesiologist 0-12 MUSv (mean of 4.0 MUSv), and for the surgeon 0-10 MUSv
(mean of 3.6 MUSv). In a comparison between the results of this study and
published literature on occupational exposures from veterinary FDG PET/CT
procedures, Cu-ATSM veterinary PET/CT procedures, on a per patient bias, exposed
workers to less radiation.
PMID- 26425990
TI - Mitochondrial capture enriches mito-DNA 100 fold, enabling PCR-free mitogenomics
biodiversity analysis.
AB - Biodiversity analyses based on next-generation sequencing (NGS) platforms have
developed by leaps and bounds in recent years. A PCR-free strategy, which can
alleviate taxonomic bias, was considered as a promising approach to delivering
reliable species compositions of targeted environments. The major impediment of
such a method is the lack of appropriate mitochondrial DNA enrichment ways.
Because mitochondrial genomes (mitogenomes) make up only a small proportion of
total DNA, PCR-free methods will inevitably result in a huge excess of data
(>99%). Furthermore, the massive volume of sequence data is highly demanding on
computing resources. Here, we present a mitogenome enrichment pipeline via a gene
capture chip that was designed by virtue of the mitogenome sequences of the 1000
Insect Transcriptome Evolution project (1KITE, www.1kite.org). A mock sample
containing 49 species was used to evaluate the efficiency of the mitogenome
capture method. We demonstrate that the proportion of mitochondrial DNA can be
increased by approximately 100-fold (from the original 0.47% to 42.52%).
Variation in phylogenetic distances of target taxa to the probe set could in
principle result in bias in abundance. However, the frequencies of input taxa
were largely maintained after capture (R(2) = 0.81). We suggest that our
mitogenome capture approach coupled with PCR-free shotgun sequencing could
provide ecological researchers an efficient NGS method to deliver reliable
biodiversity assessment.
PMID- 26425991
TI - Active biomonitoring with Corbicula for USEPA priority pollutant and metal
sources in the Anacostia River (DC, Maryland, USA).
AB - The freshwater Anacostia River watershed (Maryland, DC, USA) was surveyed for the
sources of bioavailable US Environmental Protection Agency (USEPA) Priority
Pollutants and toxic metals by active biomontoring (ABM) using the freshwater
Asiatic clam Corbicula fluminea. The Anacostia River is a 456 km(2) tributary of
the tidal freshwater Potomac River that includes the city of Washington, DC where
edible fish are highly contaminated with PCBs and chlordane. From 1999 to 2011,
Corbicula were collected for ABM from a Potomac reference site and translocated
in cages placed at 45 sites in the tidal and nontidal Anacostia watershed.
Minimum clam mortality and maximum contaminant bioaccumulation was with 2-week
translocation. The clam tissues (28-50) were combined at sites and analyzed by
TestAmerica for 66 USEPA Priority Pollutants plus technical chlordane, benz(e)
pyrene, and 6 metals (As, Cd, Cr, Cu, Fe, Pb). Tissue contaminants reflected
water, not sediment, levels. To compare sites, all contaminant data above
detection or reference were grouped as total metals (TMET), total polycyclic
aromatic hydrocarbons (TPAH), total PCB congeners (TPCB), total pesticides
(TPEST), and total technical chlordane (TCHL). Tidal Anacostia ABM found highest
TPAH and TCHL upstream at Bladensburg Marina (MD) except for TCHL at site PP near
the confluence. Five nontidal MD subtributaries (94% of flow) had 17 sites with
bioavailable TPAH, TPCB, or TCHL 2 to 3 times higher than found at the toxic
sediment "hotspots" near Washington. The only TMET noted was Fe at 1 site. TPAH
in MD subtributaries was highest near industrial parks and Metro stations. A
naphthalene spill was detected in Watts Branch. TPCB (low molecular weight)
originated upstream at 1 industrial park. Total technical chlordane (80% of
TPEST) was 2 to 5 times the US Food and Drug Administration action in 4 nontidal
tributaries where heptachlor indicated legacy chlordane dumpsites. Total
technical chlordane fell to reference below a stormwater pond, suggesting
transport via suspended sediment. Controlling the formation and movement of
contaminated TSS in MD should enable the uncontaminated-sediment capping of
Washington DC's toxic-sediment "hot-spots" that are presently considered
responsible for fish contamination. Integr Environ Assess Manag 2016;12:548-558.
(c) 2015 SETAC.
PMID- 26425992
TI - The relationship between women's attitude towards menopause and menopausal
symptoms among postmenopausal women.
AB - OBJECTIVES: The purpose of this study is to assess the symptoms of menopausal
women as well as the relationship between women's attitude towards menopause and
menopausal symptoms. METHOD: This studied, following a cross-sectional method,
included 349 selected postmenopausal women attending health care centers. The
data was collected using the attitude toward menopause (ATM) checklist and
Menopause-Specific Quality of Life (MENQOL) questionnaires. RESULTS: The most
common menopausal symptoms were physical with joint and muscle pain. The highest
mean score belongs to vasomotor symptoms (1.37 +/- 1.43), followed by
psychosocial (1.32 +/- 1.16), physical (1.22 +/- 0.96), and sexual (0.91 +/-
0.94) symptoms. Attitude toward menopause was significantly influenced by sweat
nights, poor memory, and sleeplessness. The marital status and educational level
of the husband were the only demographic factors affecting the severity of
menopausal symptoms. CONCLUSION: This study provides deeper insights about the
relationship between attitudes towards menopause and menopausal symptoms, which
can guide health-care professionals towards providing an optimal package.
PMID- 26425993
TI - Statistical modeling of nitrogen-dependent modulation of root system architecture
in Arabidopsis thaliana.
AB - Plant root development is strongly affected by nutrient availability. Despite the
importance of structure and function of roots in nutrient acquisition,
statistical modeling approaches to evaluate dynamic and temporal modulations of
root system architecture in response to nutrient availability have remained as
widely open and exploratory areas in root biology. In this study, we developed a
statistical modeling approach to investigate modulations of root system
architecture in response to nitrogen availability. Mathematical models were
designed for quantitative assessment of root growth and root branching phenotypes
and their dynamic relationships based on hierarchical configuration of primary
and lateral roots formulating the fishbone-shaped root system architecture in
Arabidopsis thaliana. Time-series datasets reporting dynamic changes in root
developmental traits on different nitrate or ammonium concentrations were
generated for statistical analyses. Regression analyses unraveled key parameters
associated with: (i) inhibition of primary root growth under nitrogen limitation
or on ammonium; (ii) rapid progression of lateral root emergence in response to
ammonium; and (iii) inhibition of lateral root elongation in the presence of
excess nitrate or ammonium. This study provides a statistical framework for
interpreting dynamic modulation of root system architecture, supported by meta
analysis of datasets displaying morphological responses of roots to diverse
nitrogen supplies.
PMID- 26425996
TI - Plasticity in oscillatory coupling between hippocampus and cortex.
AB - Neural oscillations observed in local field potentials (LFP) represent gross
cellular activity near the recording electrode. Coupling of oscillations in
distributed brain circuits has been proposed to enhance communication across the
circuits, and the plasticity in oscillatory coupling can underlie flexible task
learning, but the direct evidence has been lacking. Recently, evidence for
plasticity in oscillatory coupling in theta, beta and gamma bands has been
obtained in memory circuits consisted of the hippocampus and its connected areas,
suggesting importance of oscillatory coupling plasticity in memory processing. I
hypothesize that such plasticity in oscillatory coupling could be a key mechanism
for enhancing inter-regional neural communication, especially in the entorhinal
hippocampal and prefrontal-hippocampal memory circuits that underlie formation,
control and retrieval of memory.
PMID- 26425994
TI - HDL cholesterol and stroke risk: The Multi-Ethnic Study of Atherosclerosis.
AB - BACKGROUND AND PURPOSE: Accurate identification of risk factors for stroke is
important for public health promotion and disease prevention. HDL cholesterol is
a potential risk factor, yet its role in stroke risk is unclear, as is whether
HDL cholesterol content or particle number might be a better indicator of stroke
risk. Furthermore, the degree to which ethnicity moderates the risk is unknown.
As such, the current study examines the associations between incident stroke and
both HDL cholesterol concentration and particle number, and assesses the
moderating role of race and ethnicity. METHODS: The sample is a racially diverse
cohort of US adults between the ages of 45-84 years enrolled in the Multi-Ethnic
Study of Atherosclerosis between 2000 and 2002 and followed until December 2011.
The associations among cholesterol content and stroke risk, particle number and
stroke risk, and the interaction with race were explored. RESULTS: The incidence
of stroke was 2.6%. HDL cholesterol concentration (mmol/L) (Hazard Ratio (HR) =
.56; 95% Confidence Interval (CI): .312-.988) and number of large HDL particles
(MUmol/L) (HR = .52, CI: .278-.956) were associated with lower stroke risk. When
interactions with race were evaluated, the relationship between both HDL
variables and stroke were significant in Blacks, but not other races.
CONCLUSIONS: Higher HDL cholesterol and a higher concentration of large particles
are associated with lower risk of stroke in Blacks. Further research is needed to
elucidate the mechanisms by which HDL subfractions may differentially affect
stroke outcome in different races/ethnicities.
PMID- 26425998
TI - Hydroxymethyl Salicylaldehyde Auxiliary for a Glycine-Dependent Amide-Forming
Ligation.
AB - A new amide-forming ligation that requires a glycine or a primary amine at the
linkage site is described herein. The distinguishing feature of this ligation is
its reliance on an O-hydroxymethyl salicylaldehyde ester at the C-terminus which
allows, via an N,O-acetal intermediate, the formation of a native peptide bond.
PMID- 26425997
TI - Mainstream wastewater treatment in integrated fixed film activated sludge (IFAS)
reactor by partial nitritation/anammox process.
AB - In this study the system based on the combination of biofilm and activated sludge
(IFAS - integrated fixed film activated sludge) was tested and compared with a
system that relies only on biofilm (MBBR - moving bed biofilm reactor) for
nitrogen removal from municipal wastewater by deammonification process. By
introduction of suspended biomass into MBBR the nitrogen removal efficiency
increased from 36 +/- 3% to 70 +/- 4% with simultaneous 3-fold increase of
nitrogen removal rate. Results of batch tests and continuous reactor operation
showed that organotrophic nitrate reduction to nitrite, followed by anammox
reaction contributed to this high removal efficiency. After sCOD/NH4-N ratio
decreased from 1.8 +/- 0.2 to 1.3 +/- 0.1 removal efficiency decreased to 52 +/-
4%, while still maintaining 150% higher removal rate, comparing to MBBR. Activity
tests revealed that affinity of NOB to oxygen is higher than affinity of AOB with
half-saturation constants of 0.05 and 0.41 mg/L, respectively.
PMID- 26425999
TI - Bioassay-Guided Isolation and Identification of Xanthine Oxidase Inhibitory
Constituents from the Leaves of Perilla frutescens.
AB - Activity-directed fractionation and purification processes were employed to
identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla
frutescens. The total extract was evaluated in vitro on XO inhibitory activity
and in vivo in an experimental model with potassium oxonate-induced hyperuricemia
in mice which was used to evaluate anti-hyperuricemic activity. The crude extract
showed expressive urate-lowering activity results. Solvent partitioning of the
total extract followed by macroporous resin column chromatography of the n
butanol extract yielded four extracts and eluted parts. Among them, only the 70%
ethanol eluted part of the n-butanol extract showed strong activity and therefore
was subjected to separation and purification using various chromatographic
techniques. Five compounds showing potent activity were identified by comparing
their spectral data with literature values to be caffeic acid, vinyl caffeate,
rosmarinic acid, methyl rosmarinate, and apigenin. These results indicate that
pending further study, these compounds could be used as novel natural product
agents for the treatment of hyperuricemia.
PMID- 26426000
TI - Amination of Aryl Halides and Esters Using Intensified Continuous Flow
Processing.
AB - Significant process intensification of the amination reactions of aryl halides
and esters has been demonstrated using continuous flow processing. Using this
technology traditionally difficult amination reactions have been performed safely
at elevated temperatures. These reactions were successfully conducted on
laboratory scale coil reactor modules with 1 mm internal diameter (ID) and on a
preparatory scale tubular reactor with 6 mm ID containing static mixers.
PMID- 26426001
TI - Methanolic Extract of Ganoderma lucidum Induces Autophagy of AGS Human Gastric
Tumor Cells.
AB - Ganoderma lucidum is one of the most widely studied mushroom species,
particularly in what concerns its medicinal properties. Previous studies
(including those from some of us) have shown some evidence that the methanolic
extract of G. lucidum affects cellular autophagy. However, it was not known if it
induces autophagy or decreases the autophagic flux. The treatment of a gastric
adenocarcinoma cell line (AGS) with the mushroom extract increased the formation
of autophagosomes (vacuoles typical from autophagy). Moreover, the cellular
levels of LC3-II were also increased, and the cellular levels of p62 decreased,
confirming that the extract affects cellular autophagy. Treating the cells with
the extract together with lysossomal protease inhibitors, the cellular levels of
LC3-II and p62 increased. The results obtained proved that, in AGS cells, the
methanolic extract of G. lucidum causes an induction of autophagy, rather than a
reduction in the autophagic flux. To our knowledge, this is the first study
proving that statement.
PMID- 26426002
TI - Phytotoxic Potential and Biological Activity of Three Synthetic Coumarin
Derivatives as New Natural-Like Herbicides.
AB - Coumarin is a natural compound well known for its phytotoxic potential. In the
search for new herbicidal compounds to manage weeds, three synthetic derivatives
bearing the coumarin scaffold (1-3), synthesized by a carbonylative
organometallic approach, were in vitro assayed on germination and root growth of
two noxious weeds, Amaranthus retroflexus and Echinochloa crus-galli. Moreover,
the synthetic coumarins 1-3 were also in vitro assayed on seedlings growth of the
model species Arabidopsis thaliana to identify the possible physiological
targets. All molecules strongly affected seed germination and root growth of both
weeds. Interestingly, the effects of synthetic coumarins on weed germination were
higher than template natural coumarin, pointing out ED50 values ranging from 50
115 uM. Moreover, all synthetic coumarins showed a strong phytotoxic potential on
both Arabidopsis shoot and root growth, causing a strong reduction in shoot fresh
weight (ED50 values <= 60 uM), accompanied by leaf development and a decrease in
pigment content. Furthermore, they caused a strong alteration in root growth
(ED50 values <= 170 uM) and morphology with evident alterations in root tip
anatomy. Taken together, our results highlight the promising potential herbicidal
activity of these compounds.
PMID- 26426003
TI - Activity of Polyphenolic Compounds against Candida glabrata.
AB - Opportunistic mycoses increase the morbidity and mortality of immuno-compromised
patients. Five Candida species have been shown to be responsible for 97% of
worldwide cases of invasive candidiasis. Resistance of C. glabrata and C. krusei
to azoles has been reported, and new, improved antifungal agents are needed. The
current study was designed to evaluatethe activity of various polyphenolic
compounds against Candida species. Antifungal activity was evaluated following
the M27-A3 protocol of the Clinical and Laboratory Standards Institute, and
antioxidant activity was determined using the DPPH assay. Myricetin and baicalein
inhibited the growth of all species tested. This effect was strongest against C.
glabrata, for which the minimum inhibitory concentration (MIC) value was lower
than that of fluconazole. The MIC values against C. glabrata for myricitrin,
luteolin, quercetin, 3-hydroxyflavone, and fisetin were similar to that of
fluconazole. The antioxidant activity of all compounds was confirmed, and
polyphenolic compounds with antioxidant activity had the greatest activity
against C. glabrata. The structure and position of their hydroxyl groups appear
to influence their activity against C. glabrata.
PMID- 26426004
TI - Potent Activities of Roemerine against Candida albicans and the Underlying
Mechanisms.
AB - Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of
Fibraurea recisa, and it has been demonstrated to have certain antifungal
activity. This study aimed to investigate the antifungal activity of RM and the
underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal
activity of RM was evaluated by a series of experiments, including the XTT
reduction assay, confocal laser scanning microscopy assay, scanning electron
microscope assay. Results showed that 1 MUg/mL RM inhibited biofilm formation
significantly (p < 0.01) both in Spider medium and Lee's medium. In addition, RM
could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent
manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6,
HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 MUg/mL RM
treatment. Furthermore, the toxicity of RM was investigated using C. elegans
worms, three cancer cells and one normal cell. The date showed that RM had no
significant toxicity. In conclusion, RM could inhibited the formation of C.
albicans biofilm in vitro, but it had no fungicidal effect on planktonic C.
albicans cells, and the anti-biofilm mechanism may be related to the cAMP
pathway.
PMID- 26426005
TI - Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the
Treatment of Basal Cell Carcinoma.
AB - Basal cell carcinoma (BCC) is the most common cancer in individuals with fair
skin type (I-II) and steadily increasing in incidence (70% of skin malignancy).
It is locally invasive but metastasis is usually very rare, with an estimated
incidence of 0.0028%-0.55%. Conventional therapy is surgery, especially for the H
region of the face and infiltrative lesions; in case of inoperable tumors,
radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has
become an effective treatment in the management of superficial and small nodular
BCC. PDT is a minimally invasive procedure that involves the administration of a
photo-sensibilizing agent followed by irradiation at a pre-defined wavelength;
this determines the creation of reactive oxygen species that specifically destroy
target cells. The only major side effect is pain, reported by some patients
during the irradiation. The high cure rate and excellent cosmetic outcome
requires considering this possibility for the management of patients with both
sporadic and hereditary BCC. In this article, an extensive review of the recent
literature was made, in order to clarify the role of PDT as a possible
alternative therapeutic option in the treatment of BCC.
PMID- 26426006
TI - Evaluating Osteogenic Potential of Ligamentum Flavum Cells Cultivated in
Photoresponsive Hydrogel that Incorporates Bone Morphogenetic Protein-2 for
Spinal Fusion.
AB - Regenerative medicine is increasingly important in clinical practice. Ligamentum
flava (LF) are typically removed during spine-related surgeries. LF may be a
source of cells for spinal fusion that is conducted using tissue engineering
techniques. In this investigation, LF cells of rabbits were isolated and then
characterized by flow cytometry, morphological observation, and
immunofluorescence staining. The LF cells were also cultivated in polyethylene
(glycol) diacrylate (PEGDA) hydrogels that incorporated bone morphogenetic
protein-2 (BMP-2) growth factor, to evaluate their proliferation and secretion of
ECM and differentiation in vitro. The experimental results thus obtained that the
proliferation, ECM secretion, and differentiation of the PEGDA-BMP-2 group
exceeded those of the PEGDA group during the period of cultivation. The
mineralization and histological staining results differed similarly. A nude mice
model was utilized to prove that LF cells on hydrogels could undergo osteogenic
differentiation in vivo. These experimental results also revealed that the PEGDA
BMP-2 group had better osteogenic effects than the PEGDA group following a 12
weeks after transplantation. According to all of these experimental results, LF
cells are a source of cells for spinal fusion and PEGDA-BMP-2 hydrogel is a
candidate biomaterial for spinal fusion by tissue engineering.
PMID- 26426008
TI - Polyphosphate during the Regreening of Chlorella vulgaris under Nitrogen
Deficiency.
AB - Polyphosphate (Poly-P) accumulation has been reported in Chlorella vulgaris under
nitrogen deficiency conditions with sufficient P supply, and the process has been
demonstrated to have great impact on lipid productivity. In this article, the
utilization of polyphosphates and the regreening process under N resupplying
conditions, especially for lipid production reviving, were investigated. This
regreening process was completed within approximately 3-5 days. Polyphosphates
were first degraded within 3 days in the regreening process, with and without an
external P supply, and the degradation preceded the assimilation of phosphate in
the media with an external P offering. Nitrate assimilation was markedly
influenced by the starvation of P after polyphosphates were exhausted in the
medium without external phosphates, and then the reviving process of biomass and
lipid production was strictly impeded. It is, thus, reasonable to assume that
simultaneous provision of external N and P is essential for overall biodiesel
production revival during the regreening process.
PMID- 26426007
TI - Dangerous Liaisons: Caspase-11 and Reactive Oxygen Species Crosstalk in Pathogen
Elimination.
AB - Recently, the focus of murine caspase-11 and human orthologs caspase-4, -5
research has been on their novel function to induce noncanonical inflammasome
activation in direct response to Gram-negative bacterial infection. On the other
hand, a new role in anti-bacterial autophagy has been attributed to caspase-11,
4 and -5, which currently stands largely unexplored. In this review, we connect
lately emerged evidence that suggests these caspases have a key role in anti
bacterial autophagy and discuss the growing implications of a danger molecule-
extracellular ATP--and NADPH oxidase-mediated ROS generation as novel inducers of
human caspase-4, -5 signaling during infection. We also highlight the adeptness
of persistent pathogens like Porphyromonas gingivalis, a Gram-negative anaerobe
and successful colonizer of oral mucosa, to potentially interfere with the
activated caspase-4 pathway and autophagy. While, the ability of caspase-4, -5 to
promote autophagolysosomal fusion is not well understood, the abundance of
caspase-4 in skin and other mucosal epithelial cells implies an important role
for caspase-4 in mucosal defense, supporting the view that caspase-4, -5 may play
a non-redundant part in innate immunity. Thus, this review will join the
currently disconnected cutting-edge research thereby proposing a working model
for regulation of caspase-4, -5 in pathogen elimination via cellular-trafficking.
PMID- 26426009
TI - Alkyl Chain Growth on a Transition Metal Center: How Does Iron Compare to
Ruthenium and Osmium?
AB - Industrial Fischer-Tropsch processes involve the synthesis of hydrocarbons
usually on metal surface catalysts. On the other hand, very few homogeneous
catalysts are known to perform a Fischer-Tropsch style of reaction. In recent
work, we established the catalytic properties of a diruthenium-platinum carbene
complex, [(CpRu)2(MU2-H) (MU2-NHCH3)(MU3-C)PtCH3(P(CH3)3)2](CO)n+ with n=0, 2 and
Cp=eta5-C5(CH3)5, and showed it to react efficiently by initial hydrogen atom
transfer followed by methyl transfer to form an alkyl chain on the Ru-center. In
particular, the catalytic efficiency was shown to increase after the addition of
two CO molecules. As such, this system could be viewed as a potential homogeneous
Fischer-Tropsch catalyst. Herein, we have engineered the catalytic center of the
catalyst and investigated the reactivity of trimetal carbene complexes of the
same type using iron, ruthenium and osmium at the central metal scaffold. The
work shows that the reactivity should increase from diosmium to diruthenium to
diiron; however, a non-linear trend is observed due to multiple factors
contributing to the individual barrier heights. We identified all individual
components of these reaction steps in detail and established the difference in
reactivity of the various complexes.
PMID- 26426010
TI - Combination of MiR-378 and MiR-210 Serum Levels Enables Sensitive Detection of
Renal Cell Carcinoma.
AB - Serum microRNAs are emerging as a clinically useful tool for early and non
invasive detection of various cancer types including renal cell carcinoma (RCC).
Based on our previous results, we performed the study to analyze circulating
serum miR-378 and miR-210 in patients with various histological subtypes of RCC.
RNA was purified from blood serum samples of 195 RCC patients and 100 healthy
controls. The levels of miR-378 and miR-210 in serum were determined absolutely
using quantitative real-time PCR. Pre- and postoperative levels of both microRNAs
were compared in 20 RCC patients. Significantly increased serum levels of both
miR-378 and miR-210 enabled to clearly distinguish RCC patients and healthy
controls with 80% sensitivity and 78% specificity if analyzed in combination
(p<0.0001), and their levels significantly decreased in the time period of three
months after radical nephrectomy (p<0.0001). Increased level of miR-378
positively correlates with disease-free survival (p=0.036) and clinical stage
(p=0.0476). The analysis of serum miR-378 and miR-210 proved their potential to
serve as powerful non-invasive diagnostic and prognostic biomarkers in RCC.
PMID- 26426011
TI - Heavy Metal Induced Antibiotic Resistance in Bacterium LSJC7.
AB - Co-contamination of antibiotics and heavy metals prevails in the environment, and
may play an important role in disseminating bacterial antibiotic resistance, but
the selective effects of heavy metals on bacterial antibiotic resistance is
largely unclear. To investigate this, the effects of heavy metals on antibiotic
resistance were studied in a genome-sequenced bacterium, LSJC7. The results
showed that the presence of arsenate, copper, and zinc were implicated in
fortifying the resistance of LSJC7 towards tetracycline. The concentrations of
heavy metals required to induce antibiotic resistance, i.e., the minimum heavy
metal concentrations (MHCs), were far below (up to 64-fold) the minimum
inhibition concentrations (MIC) of LSJC7. This finding indicates that the
relatively low heavy metal levels in polluted environments and in treated humans
and animals might be sufficient to induce bacterial antibiotic resistance. In
addition, heavy metal induced antibiotic resistance was also observed for a
combination of arsenate and chloramphenicol in LSJC7, and copper/zinc and
tetracycline in antibiotic susceptible strain Escherichia coli DH5alpha. Overall,
this study implies that heavy metal induced antibiotic resistance might be
ubiquitous among various microbial species and suggests that it might play a role
in the emergence and spread of antibiotic resistance in metal and antibiotic co
contaminated environments.
PMID- 26426012
TI - Nimbolide Induces ROS-Regulated Apoptosis and Inhibits Cell Migration in
Osteosarcoma.
AB - Osteosarcoma (OS) is a primary malignant tumor of bone and is most prevalent in
children and adolescents. OS is frequently associated with pulmonary metastasis,
which is the main cause of OS-related mortality. OS has a poor prognosis and is
often unresponsive to conventional chemotherapy. In this study, we determined
that Nimbolide, a novel anti-cancer therapy, acts by modulating multiple
mechanisms in osteosarcoma cells. Nimbolide induces apoptosis by increasing
endoplasmic reticulum (ER) stress, mitochondrial dysfunction, accumulation of
reactive oxygen species (ROS), and finally, caspase activation. We also
determined that Nimbolide inhibits cell migration, which is crucial for
metastasis, by reducing the expression of integrin alphavbeta5. In addition, our
results demonstrate that integrin alphavbeta5 expression is modulated by the
PI3K/Akt and NF-kappaB signaling cascade. Nimbolide has potential as an anti
tumor drug given its multifunctional effects in OS. Collectively, these results
help us to understand the mechanisms of action of Nimbolide and will aid in the
development of effective therapies for OS.
PMID- 26426015
TI - Performance Evaluation of Wearable Sensor Systems: A Case Study in Moderate-Scale
Deployment in Hospital Environment.
AB - A wearable sensor system enables continuous and remote health monitoring and is
widely considered as the next generation of healthcare technology. The
performance, the packet error rate (PER) in particular, of a wearable sensor
system may deteriorate due to a number of factors, particularly the interference
from the other wearable sensor systems in the vicinity. We systematically
evaluate the performance of the wearable sensor system in terms of PER in the
presence of such interference in this paper. The factors that affect the
performance of the wearable sensor system, such as density, traffic load, and
transmission power in a realistic moderate-scale deployment case in hospital are
all considered. Simulation results show that with 20% duty cycle, only 68.5% of
data transmission can achieve the targeted reliability requirement (PER is less
than 0.05) even in the off-peak period in hospital. We then suggest some
interference mitigation schemes based on the performance evaluation results in
the case study.
PMID- 26426013
TI - Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on
Aged Pancreas after Life-Long Coenzyme Q Addition.
AB - An adequate pancreatic structure is necessary for optimal organ function.
Structural changes are critical in the development of age-related pancreatic
disorders. In this context, it has been reported that different pancreatic
compartments from rats were affected according to the fat composition consumed.
Since there is a close relationship between mitochondria, oxidative stress and
aging, an experimental approach has been developed to gain more insight into this
process in the pancreas. A low dosage of coenzyme Q was administered life-long in
rats in order to try to prevent pancreatic aging-related alterations associated
to some dietary fat sources. According to that, three groups of rats were fed
normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive,
sunflower, or fish oil was included as unique fat source. Pancreatic samples for
microscopy and blood samples were collected at the moment of euthanasia. The main
finding is that CoQ supplementation gives different results according to fat used
in diet. When sunflower oil was the main fat in the diet, CoQ supplementation
seems to improve endocrine pancreas structure and in particular beta-cell mass
resembling positive effects of virgin olive oil. Conversely, CoQ intake does not
seem to improve the structural alterations of exocrine compartment previously
observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations
associated to the chronic intake of some dietary fat sources.
PMID- 26426016
TI - Rate Adaptive Based Resource Allocation with Proportional Fairness Constraints in
OFDMA Systems.
AB - Orthogonal frequency division multiple access (OFDMA), which is widely used in
the wireless sensor networks, allows different users to obtain different
subcarriers according to their subchannel gains. Therefore, how to assign
subcarriers and power to different users to achieve a high system sum rate is an
important research area in OFDMA systems. In this paper, the focus of study is on
the rate adaptive (RA) based resource allocation with proportional fairness
constraints. Since the resource allocation is a NP-hard and non-convex
optimization problem, a new efficient resource allocation algorithm ACO-SPA is
proposed, which combines ant colony optimization (ACO) and suboptimal power
allocation (SPA). To reduce the computational complexity, the optimization
problem of resource allocation in OFDMA systems is separated into two steps. For
the first one, the ant colony optimization algorithm is performed to solve the
subcarrier allocation. Then, the suboptimal power allocation algorithm is
developed with strict proportional fairness, and the algorithm is based on the
principle that the sums of power and the reciprocal of channel-to-noise ratio for
each user in different subchannels are equal. To support it, plenty of simulation
results are presented. In contrast with root-finding and linear methods, the
proposed method provides better performance in solving the proportional resource
allocation problem in OFDMA systems.
PMID- 26426014
TI - An Overview of Predictors for Intrinsically Disordered Proteins over 2010-2014.
AB - The sequence-structure-function paradigm of proteins has been changed by the
occurrence of intrinsically disordered proteins (IDPs). Benefiting from the
structural disorder, IDPs are of particular importance in biological processes
like regulation and signaling. IDPs are associated with human diseases, including
cancer, cardiovascular disease, neurodegenerative diseases, amyloidoses, and
several other maladies. IDPs attract a high level of interest and a substantial
effort has been made to develop experimental and computational methods. So far,
more than 70 prediction tools have been developed since 1997, within which 17
predictors were created in the last five years. Here, we presented an overview of
IDPs predictors developed during 2010-2014. We analyzed the algorithms used for
IDPs prediction by these tools and we also discussed the basic concept of various
prediction methods for IDPs. The comparison of prediction performance among these
tools is discussed as well.
PMID- 26426017
TI - Optimisation and Characterisation of Anti-Fouling Ternary SAM Layers for
Impedance-Based Aptasensors.
AB - An aptasensor with enhanced anti-fouling properties has been developed. As a case
study, the aptasensor was designed with specificity for human thrombin. The
sensing platform was developed on screen printed electrodes and is composed of a
self-assembled monolayer made from a ternary mixture of 15-base thiolated DNA
aptamers specific for human thrombin co-immobilised with 1,6-hexanedithiol (HDT)
and further passivated with 1-mercapto-6-hexanol (MCH). HDT binds to the surface
by two of its thiol groups forming alkyl chain bridges and this architecture
protects from non-specific attachment of molecules to the electrode surface.
Using Electrochemical Impedance Spectroscopy (EIS), the aptasensor is able to
detect human thrombin as variations in charge transfer resistance (Rct) upon
protein binding. After exposure to a high concentration of non-specific Bovine
Serum Albumin (BSA) solution, no changes in the Rct value were observed,
highlighting the bio-fouling resistance of the surface generated. In this paper,
we present the optimisation and characterisation of the aptasensor based on the
ternary self-assembled monolayer (SAM) layer. We show that anti-fouling
properties depend on the type of gold surface used for biosensor construction,
which was also confirmed by contact angle measurements. We further studied the
ratio between aptamers and HDT, which can determine the specificity and
selectivity of the sensing layer. We also report the influence of buffer pH and
temperature used for incubation of electrodes with proteins on detection and anti
fouling properties. Finally, the stability of the aptasensor was studied by
storage of modified electrodes for up to 28 days in different buffers and
atmospheric conditions. Aptasensors based on ternary SAM layers are highly
promising for clinical applications for detection of a range of proteins in real
biological samples.
PMID- 26426018
TI - A Note on an Improved Self-Healing Group Key Distribution Scheme.
AB - In 2014, Chen et al. proposed a one-way hash self-healing group key distribution
scheme for resource-constrained wireless networks in the journal of Sensors
(14(14):24358-24380, doi: 10.3390/ s141224358). They asserted that their Scheme 2
achieves mt-revocation capability, mt-wise forward secrecy, any-wise backward
secrecy and has mt-wise collusion attack resistance capability. Unfortunately,
this paper pointed out that their scheme does not satisfy the forward security,
mt-revocation capability and mt-wise collusion attack resistance capability.
PMID- 26426019
TI - A Feasibility Analysis of Land-Based SINS/GNSS Gravimetry for Groundwater
Resource Detection in Taiwan.
AB - The integration of the Strapdown Inertial Navigation System and Global Navigation
Satellite System (SINS/GNSS) has been implemented for land-based gravimetry and
has been proven to perform well in estimating gravity. Based on the mGal-level
gravimetry results, this research aims to construct and develop a land-based
SINS/GNSS gravimetry device containing a navigation-grade Inertial Measurement
Unit. This research also presents a feasibility analysis for groundwater resource
detection. A preliminary comparison of the kinematic velocities and accelerations
using multi-combination of GNSS data including Global Positioning System, Global
Navigation Satellite System, and BeiDou Navigation Satellite System, indicates
that three-system observations performed better than two-system data in the
computation. A comparison of gravity derived from SINS/GNSS and measured using a
relative gravimeter also shows that both agree reasonably well with a mean
difference of 2.30 mGal. The mean difference between repeat measurements of
gravity disturbance using SINS/GNSS is 2.46 mGal with a standard deviation of
1.32 mGal. The gravity variation because of the groundwater at Pingtung Plain,
Taiwan could reach 2.72 mGal. Hence, the developed land-based SINS/GNSS
gravimetry can sufficiently and effectively detect groundwater resources.
PMID- 26426020
TI - Quantitative Assessment of Parkinsonian Tremor Based on an Inertial Measurement
Unit.
AB - Quantitative assessment of parkinsonian tremor based on inertial sensors can
provide reliable feedback on the effect of medication. In this regard, the
features of parkinsonian tremor and its unique properties such as motor
fluctuations and dyskinesia are taken into account. Least-square-estimation
models are used to assess the severities of rest, postural, and action tremors.
In addition, a time-frequency signal analysis algorithm for tremor state
detection was also included in the tremor assessment method. This inertial sensor
based method was verified through comparison with an electromagnetic motion
tracking system. Seven Parkinson's disease (PD) patients were tested using this
tremor assessment system. The measured tremor amplitudes correlated well with the
judgments of a neurologist (r = 0.98). The systematic analysis of sensor-based
tremor quantification and the corresponding experiments could be of great help in
monitoring the severity of parkinsonian tremor.
PMID- 26426021
TI - A Novel Fusion-Based Ship Detection Method from Pol-SAR Images.
AB - A novel fusion-based ship detection method from polarimetric Synthetic Aperture
Radar (Pol-SAR) images is proposed in this paper. After feature extraction and
constant false alarm rate (CFAR) detection, the detection results of HH channel,
diplane scattering by Pauli decomposition and helical factor by Barnes
decomposition are fused together. The confirmed targets and potential target
pixels can be obtained after the fusion process. Using the difference degree of
the target, potential target pixels can be classified. The fusion-based ship
detection method works accurately by utilizing three different features
comprehensively. The result of applying the technique to measured Airborne
Synthetic Radar (AIRSAR) data shows that the novel detection method can achieve
better performance in both ship's detection and ship's shape preservation
compared to the result of K-means clustering method and the Notch Filter method.
PMID- 26426022
TI - Surface Plasmon Scattering in Exposed Core Optical Fiber for Enhanced Resolution
Refractive Index Sensing.
AB - Refractometric sensors based on optical excitation of surface plasmons on the
side of an optical fiber is an established sensing architecture that has enabled
laboratory demonstrations of cost effective portable devices for biological and
chemical applications. Here we report a Surface Plasmon Resonance (SPR)
configuration realized in an Exposed Core Microstructured Optical Fiber (ECF)
capable of optimizing both sensitivity and resolution. To the best of our
knowledge, this is the first demonstration of fabrication of a rough metal
coating suitable for spectral interrogation of scattered plasmonic wave using
chemical electroless plating technique on a 10 MUm diameter exposed core of the
ECF. Performance of the sensor in terms of its refractive index sensitivity and
full width at half maximum (FWHM) of SPR response is compared to that achieved
with an unstructured bare core fiber with 140 MUm core diameter. The experimental
improvement in FWHM, and therefore the detection limit, is found to be a factor
of two (75 nm for ECF in comparison to 150 nm for the large core fiber).
Refractive index sensitivity of 1800 nm/RIU was achieved for both fibers in the
sensing range of aqueous environment (1.33-1.37) suitable for biosensing
applications.
PMID- 26426023
TI - The Video Collaborative Localization of a Miner's Lamp Based on Wireless
Multimedia Sensor Networks for Underground Coal Mines.
AB - Based on wireless multimedia sensor networks (WMSNs) deployed in an underground
coal mine, a miner's lamp video collaborative localization algorithm was proposed
to locate miners in the scene of insufficient illumination and bifurcated
structures of underground tunnels. In bifurcation area, several camera nodes are
deployed along the longitudinal direction of tunnels, forming a collaborative
cluster in wireless way to monitor and locate miners in underground tunnels. Cap
lamps are regarded as the feature of miners in the scene of insufficient
illumination of underground tunnels, which means that miners can be identified by
detecting their cap-lamps. A miner's lamp will project mapping points on the
imaging plane of collaborative cameras and the coordinates of mapping points are
calculated by collaborative cameras. Then, multiple straight lines between the
positions of collaborative cameras and their corresponding mapping points are
established. To find the three-dimension (3D) coordinate location of the miner's
lamp a least square method is proposed to get the optimal intersection of the
multiple straight lines. Tests were carried out both in a corridor and a
realistic scenario of underground tunnel, which show that the proposed miner's
lamp video collaborative localization algorithm has good effectiveness,
robustness and localization accuracy in real world conditions of underground
tunnels.
PMID- 26426024
TI - Double Laser for Depth Measurement of Thin Films of Ice.
AB - The use of thin films is extensive in both science and industry. We have created
an experimental system that allows us to measure the thicknesses of thin films
(with typical thicknesses of around 1 um) in real time without the need for any
prior knowledge or parameters. Using the proposed system, we can also measure the
refractive index of the thin film material exactly under the same experimental
conditions. We have also obtained interesting results with regard to structural
changes in the solid substance with changing temperature and have observed the
corresponding behavior of mixtures of substances.
PMID- 26426025
TI - Opioid Facilitation of beta-Adrenergic Blockade: A New Pharmacological Condition?
AB - Recently, propranolol was suggested to prevent hyperlactatemia in a child with
hypovolemic shock through beta-adrenergic blockade. Though it is a known
inhibitor of glycolysis, propranolol, outside this observation, has never been
reported to fully protect against lactate overproduction. On the other hand,
literature evidence exists for a cross-talk between beta-adrenergic receptors
(protein targets of propranolol) and delta-opioid receptor. In this literature
context, it is hypothesized here that anti-diarrheic racecadotril (a pro-drug of
thiorphan, an inhibitor of enkephalinases), which, in the cited observation, was
co-administered with propranolol, might have facilitated the beta-blocker-driven
inhibition of glycolysis and resulting lactate production. The opioid-facilitated
beta-adrenergic blockade would be essentially additivity or even synergism
putatively existing between antagonism of beta-adrenergic receptors and agonism
of delta-opioid receptor in lowering cellular cAMP and dependent functions.
PMID- 26426026
TI - Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of
Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and
Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass.
AB - Health authorities worldwide have consistently recommended the regular
consumption of marine fishes and seafood to preserve memory, sustain cognitive
functions, and prevent neurodegenerative processes in humans. Shrimp, crabs,
lobster, and salmon are of particular interest in the human diet due to their
substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant
carotenoid astaxanthin (ASTA). However, the optimal ratio between these
nutraceuticals in natural sources is apparently the key factor for maximum
protection against most neuro-motor disorders. Therefore, we aimed here to
investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish
oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural
combination of both nutrients) on baseline redox balance and neuro-inflammation
indexes in cerebellum and motor cortex of Wistar rats. Significant changes in
redox metabolism were only observed upon ASTA supplementation, which reinforce
its antioxidant properties with a putative mitochondrial-centered action in rat
brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar
rats, although no redox or inflammatory index was concomitantly altered. In
summary, there is no experimental evidence that krill oil, fish oil, oralgal
biomass (minor variation), drastically change the baseline oxidative conditions
or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.
PMID- 26426027
TI - Photo-Oxidative Stress-Driven Mutagenesis and Adaptive Evolution on the Marine
Diatom Phaeodactylum tricornutum for Enhanced Carotenoid Accumulation.
AB - Marine diatoms have recently gained much attention as they are expected to be a
promising resource for sustainable production of bioactive compounds such as
carotenoids and biofuels as a future clean energy solution. To develop
photosynthetic cell factories, it is important to improve diatoms for value-added
products. In this study, we utilized UVC radiation to induce mutations in the
marine diatom Phaeodactylum tricornutum and screened strains with enhanced
accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution
(ALE) was also used in parallel to develop altered phenotypic and biological
functions in P. tricornutum and it was reported for the first time that ALE was
successfully applied on diatoms for the enhancement of growth performance and
productivity of value-added carotenoids to date. Liquid chromatography-mass
spectrometry (LC-MS) was utilized to study the composition of major pigments in
the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains
exhibited higher accumulation of fucoxanthin as well as neutral lipids compared
to their wild type counterpart. In addition to UV mutagenesis, P. tricornutum
strains developed by ALE also yielded enhanced biomass production and fucoxanthin
accumulation under combined red and blue light. In short, both UV mutagenesis and
ALE appeared as an effective approach to developing desired phenotypes in the
marine diatoms via electromagnetic radiation-induced oxidative stress.
PMID- 26426028
TI - Blood Cadmium Is Associated with Osteoporosis in Obese Males but Not in Non-Obese
Males: The Korea National Health and Nutrition Examination Survey 2008-2011.
AB - Osteoporosis in males is becoming an important health concern in an aging
society. The aim of this study was to investigate the associations between
cadmium exposure and osteoporosis by considering the effect of obesity in aged
males using a representative sample of the Korean population. Using the fourth
and fifth Korea National Health and Nutrition Examination Survey data, 1098 males
over 50 years of age were analyzed. The blood cadmium concentration was measured.
The bone mineral density in the total hip, femur neck, and lumbar spine was
measured using dual-energy X-ray absorptiometry. T-scores to determine the
presence of osteoporosis were calculated using a Korean reference. Subjects were
stratified into two groups according to obesity status (body mass index <25 kg/m2
and >=25 kg/m2). In comparison with obese subjects with blood cadmium <1.00
MUg/L, those with blood cadmium >1.50 MUg/L had odds ratios of 4.57 (95%
confidence interval [CI] 1.49-14.01) and 5.71 (95% CI 1.99-16.38) at the femur
neck and any site, respectively, after adjusting for potential confounders such
as age, serum creatinine, vitamin D deficiency, smoking, alcohol drinking, and
physical activity level. However, this association was not significant in non
obese males. In conclusion, the effect of cadmium on osteoporosis was different
by obesity status in aged males.
PMID- 26426029
TI - Healthy Aging Promotion through Neuroscientific Information-Based Strategies.
AB - To ensure the well-being of a rapidly growing elderly population, it is
fundamental to find strategies to foster healthy brain aging. With this
intention, we designed a program of scientific-based lectures aimed at
dissemination by established neuroscientists about brain function, brain
plasticity and how lifestyle influences the brain. We also carried out a pilot
study on the impact of the lectures on attendees. The objective was to provide
information to elderly people in order to encourage them to identify unhealthy
and healthy daily habits, and more importantly, to promote behavioral changes
towards healthy brain aging. Here we report on our experience. In order to
determine the impact of the lectures in the daily routine of the attendees, we
asked them to fill out questionnaires. Preliminary results indicate that
neuroscientific information-based strategies can be a useful method to have a
positive impact on the lives of elderly, increase their awareness on how to
improve brain function and promote positive lifestyle modifications. Furthermore,
based on self-reported data, we also found that through this strategy it is
possible to promote behavioral changes related to nutrition, sleep, and
realization of physical and cognitively stimulating activities. Finally, based on
the results obtained, the importance of promoting self-efficacy and the
empowerment of the older populations is highlighted.
PMID- 26426030
TI - Temporal and Spatial Simulation of Atmospheric Pollutant PM2.5 Changes and Risk
Assessment of Population Exposure to Pollution Using Optimization Algorithms of
the Back Propagation-Artificial Neural Network Model and GIS.
AB - PM2.5 pollution has become of increasing public concern because of its relative
importance and sensitivity to population health risks. Accurate predictions of
PM2.5 pollution and population exposure risks are crucial to developing effective
air pollution control strategies. We simulated and predicted the temporal and
spatial changes of PM2.5 concentration and population exposure risks, by coupling
optimization algorithms of the Back Propagation-Artificial Neural Network (BP
ANN) model and a geographical information system (GIS) in Xi'an, China, for 2013,
2020, and 2025. Results indicated that PM2.5 concentration was positively
correlated with GDP, SO2, and NO2, while it was negatively correlated with
population density, average temperature, precipitation, and wind speed. Principal
component analysis of the PM2.5 concentration and its influencing factors'
variables extracted four components that accounted for 86.39% of the total
variance. Correlation coefficients of the Levenberg-Marquardt (trainlm) and
elastic (trainrp) algorithms were more than 0.8, the index of agreement (IA)
ranged from 0.541 to 0.863 and from 0.502 to 0.803 by trainrp and trainlm
algorithms, respectively; mean bias error (MBE) and Root Mean Square Error (RMSE)
indicated that the predicted values were very close to the observed values, and
the accuracy of trainlm algorithm was better than the trainrp. Compared to 2013,
temporal and spatial variation of PM2.5 concentration and risk of population
exposure to pollution decreased in 2020 and 2025. The high-risk areas of
population exposure to PM2.5 were mainly distributed in the northern region,
where there is downtown traffic, abundant commercial activity, and more exhaust
emissions. A moderate risk zone was located in the southern region associated
with some industrial pollution sources, and there were mainly low-risk areas in
the western and eastern regions, which are predominantly residential and
educational areas.
PMID- 26426031
TI - High Cancer Burden in Elderly Chinese, 2005-2011.
AB - OBJECTIVE: Cancer risk increases with age, creating a challenge for the Chinese
health system. To inform public health policy and research, we evaluated the
cancer burden in elderly Chinese. METHODS: Based on the published Chinese Cancer
Registry Annual Report or related literature and the China Population and
Employment Statistics Yearbooks, we estimated the cancer burden of elderly
Chinese, who were representative of the Chinese population. We calculated the
cancer incidence, cancer-related mortality, potential years of life lost (PYLL),
and disability-adjusted life years (DALYs) in 2005-2011 by age, sex, district
(rural, urban), and calendar year using national cancer registry, publication,
and census data. The relative ratios (RRs) were determined between the elderly
(>=60 years) and young (<60 years). RESULTS: Cancer incidence and related
mortality in the elderly were 8.47 and 13.96 times, respectively, those in the
young. The PYLL and DALY rates of the elderly were 1.63 and 5.00 times,
respectively, those in the young. The PYLL and DALY rates for elderly men and
rural districts were higher than for elderly women and urban districts. The RRs
for male sex and rural districts were higher than for female sex and urban
districts. RRs increased sharply from 2005 to 2011. CONCLUSIONS: The cancer
burden in elderly Chinese was higher in men and rural districts than in women and
urban districts, which creates considerable challenges for the Chinese health
care system. Comprehensive measures for cancer prevention and treatment in the
elderly are needed.
PMID- 26426032
TI - Water Environmental Capacity Analysis of Taihu Lake and Parameter Estimation
Based on the Integration of the Inverse Method and Bayesian Modeling.
AB - An integrated approach using the inverse method and Bayesian approach, combined
with a lake eutrophication water quality model, was developed for parameter
estimation and water environmental capacity (WEC) analysis. The model was used to
support load reduction and effective water quality management in the Taihu Lake
system in eastern China. Water quality was surveyed yearly from 1987 to 2010.
Total nitrogen (TN) and total phosphorus (TP) were selected as water quality
model variables. Decay rates of TN and TP were estimated using the proposed
approach. WECs of TN and TP in 2011 were determined based on the estimated decay
rates. Results showed that the historical loading was beyond the WEC, thus,
reduction of nitrogen and phosphorus input is necessary to meet water quality
goals. Then WEC and allowable discharge capacity (ADC) in 2015 and 2020 were
predicted. The reduction ratios of ADC during these years were also provided. All
of these enable decision makers to assess the influence of each loading and
visualize potential load reductions under different water quality goals, and then
to formulate a reasonable water quality management strategy.
PMID- 26426033
TI - A Comparative Land Use-Based Analysis of Noise Pollution Levels in Selected Urban
Centers of Nigeria.
AB - Growth in the commercialization, mobility and urbanization of human settlements
across the globe has greatly exposed world urban population to potentially
harmful noise levels. The situation is more disturbing in developing countries
like Nigeria, where there are no sacrosanct noise laws and regulations. This
study characterized noise pollution levels in Ibadan and Ile-Ife, two urban areas
of Southwestern Nigeria that have experienced significant increases in population
and land use activities. Eight hundred noise measurements, taken at 20 different
positions in the morning, afternoon, and evening of carefully selected weekdays,
in each urban area, were used for this study. Findings put the average noise
levels in the urban centers at between 53 dB(A) and 89 dB (A), a far cry from the
World Health Organization (WHO) permissible limits in all the land use types,
with highest noise pollution levels recorded for transportation, commercial,
residential and educational land use types. The result of the one-way ANOVA test
carried out on the dependent variable noise and fixed factor land use types
reveals a statistically significant mean noise levels across the study area
(F(3,34) = 15.13, p = 0.000). The study underscores noise pollution monitoring
and the urgent need to control urban noise pollution with appropriate and
effective policies.
PMID- 26426034
TI - Nipple Pain in Breastfeeding Mothers: Incidence, Causes and Treatments.
AB - BACKGROUND: Persistent nipple pain is one of the most common reasons given by
mothers for ceasing exclusive breastfeeding. We aimed to determine the frequency
of nipple pain as a reason for consultation, the most common attributed
aetiologies, and the effectiveness of the advice and treatment given. METHODS:
All consultations at the Breast Feeding Centre of Western Australia (WA) were
audited over two six-month periods in 2011 (n = 469) and 2014 (n = 708).
Attributed cause(s) of nipple pain, microbiology results, treatment(s) advised,
and resolution of pain were recorded. RESULTS: Nipple pain was one of the reasons
for consultation in 36% of cases. The most common attributed cause of nipple pain
was incorrect positioning and attachment, followed by tongue tie, infection,
palatal anomaly, flat or inverted nipples, mastitis, and vasospasm. Advice
included correction of positioning and attachment, use of a nipple shield,
resting the nipples and expressing breastmilk, frenotomy, oral antibiotics,
topical treatments, and cold or warm compresses. Pain was resolving or resolved
in 57% of cases after 18 days (range 2-110). CONCLUSION: The multiple attributed
causes of nipple pain, possibly as a result of a cascade of events, suggests that
effective early lactation management for prevention of nipple pain and early
diagnosis and effective treatment are crucial to avoid early weaning.
PMID- 26426035
TI - Comparison of Hourly PM2.5 Observations Between Urban and Suburban Areas in
Beijing, China.
AB - Hourly PM2.5 observations collected at 12 stations over a 1-year period are used
to identify variations between urban and suburban areas in Beijing. The data
demonstrates a unique monthly variation form, as compared with other major
cities. Urban areas suffer higher PM2.5 concentration (about 92 MUg/m3) than
suburban areas (about 77 MUg/m3), and the average PM2.5 concentration in cold
season (about 105 MUg/m3) is higher than warm season (about 78 MUg/m3). Hourly
PM2.5 observations exhibit distinct seasonal, diurnal and day-of-week variations.
The diurnal variation of PM2.5 is observed with higher concentration at night and
lower value at daytime, and the cumulative growth of nighttime (22:00 p.m. in
winter) PM2.5 concentration maybe due to the atmospheric stability. Moreover,
annual average PM2.5 concentrations are about 18 MUg/m3 higher on weekends than
weekdays, consistent with driving restrictions on weekdays. Additionally, the
nighttime peak in weekdays (21:00 p.m.) is one hour later than weekends (20:00
p.m.) which also shows the evidence of human activity. These observed facts
indicate that the variations of PM2.5 concentration between urban and suburban
areas in Beijing are influenced by complex meteorological factors and human
activities.
PMID- 26426036
TI - Filoviruses: One of These Things is (not) Like the Other.
AB - The family Filoviridae contains several of the most deadly pathogens known to
date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to
Ebola virus (EBOV) infection, highlights the need for active and broad research
into filovirus pathogenesis. However, in comparison, the seven other known
filovirus family members are significantly understudied. Many of these, including
Marburgviruses and Ebolaviruses other than EBOV, are also highly virulent and
fully capable of causing widespread epidemics. This review places the focus on
these non-EBOV filoviruses, including known immunological and pathological data.
The available animal models, research tools and currently available therapeutics
will also be discussed along with an emphasis in the large number of current gaps
in knowledge of these less highlighted filoviruses. It is evident that much
research is yet to be done in order to bring the non-EBOV filovirus field to the
forefront of current research and, importantly, to the development of more
effective vaccines and therapeutics to combat potential future outbreaks.
PMID- 26426037
TI - Differentially-Expressed Pseudogenes in HIV-1 Infection.
AB - Not all pseudogenes are transcriptionally silent as previously thought.
Pseudogene transcripts, although not translated, contribute to the non-coding RNA
pool of the cell that regulates the expression of other genes. Pseudogene
transcripts can also directly compete with the parent gene transcripts for mRNA
stability and other cell factors, modulating their expression levels. Tissue
specific and cancer-specific differential expression of these "functional"
pseudogenes has been reported. To ascertain potential pseudogene:gene
interactions in HIV-1 infection, we analyzed transcriptomes from infected and
uninfected T-cells and found that 21 pseudogenes are differentially expressed in
HIV-1 infection. This is interesting because parent genes of one-third of these
differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and
parent genes of half of these pseudogenes are involved in different viral
infections. Our bioinformatics analysis identifies candidate pseudogene:gene
interactions that may be of significance in HIV-1 infection. Experimental
validation of these interactions would establish that retroviruses exploit this
newly-discovered layer of host gene expression regulation for their own benefit.
PMID- 26426039
TI - Solid Microneedles for Transdermal Delivery of Amantadine Hydrochloride and
Pramipexole Dihydrochloride.
AB - The aim of this project was to study the influence of microneedles on transdermal
delivery of amantadine hydrochloride and pramipexole dihydrochloride across
porcine ear skin in vitro. Microchannel visualization studies were carried out
and characterization of the microchannel depth was performed using confocal laser
scanning microscopy (CLSM) to demonstrate microchannel formation following
microneedle roller application. We also report, for the first time, the use of
TA.XT Plus Texture Analyzer to characterize burst force in pig skin for
transdermal drug delivery experiments. This is the force required to rupture pig
skin. The mean passive flux of amantadine hydrochloride, determined using a
developed LC-MS/MS technique, was 22.38 +/- 4.73 ug/cm2/h, while the mean flux
following the use of a stainless steel microneedle roller was 49.04 +/- 19.77
ug/cm2/h. The mean passive flux of pramipexole dihydrochloride was 134.83 +/-
13.66 ug/cm2/h, while the flux following the use of a stainless steel microneedle
roller was 134.04 +/- 0.98 ug/cm2/h. For both drugs, the difference in flux
values following the use of solid stainless steel microneedle roller was not
statistically significantly (p > 0.05). Statistical analysis was carried out
using the Mann-Whitney Rank sum test.
PMID- 26426038
TI - Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance.
AB - The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial
health and economic burden in both developing and developed countries.
Controlling the spread of HCV through behavioural prevention strategies has met
with limited success and vaccine development remains slow. The development of
antiviral therapeutic agents has also been challenging, primarily due to the lack
of efficient cell culture and animal models for all HCV genotypes, as well as the
large genetic diversity between HCV strains. On the other hand, the use of
interferon-alpha-based treatments in combination with the guanosine analogue,
ribavirin, achieved limited success, and widespread use of these therapies has
been hampered by prevalent side effects. For more than a decade, the HCV RNA
dependent RNA polymerase (RdRp) has been targeted for antiviral development, and
direct-acting antivirals (DAA) have been identified which bind to one of at least
six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly
effective and well tolerated antiviral treatment for HCV infection. Here we
review the different classes of RdRp inhibitors and their mode of action against
HCV. Furthermore, the mechanism of antiviral resistance to each class is
described, including naturally occurring resistance-associated variants (RAVs) in
different viral strains and genotypes. Finally, we review the impact of these
RAVs on treatment outcomes with the newly developed regimens.
PMID- 26426040
TI - Methylene Blue-Loaded Dissolving Microneedles: Potential Use in Photodynamic
Antimicrobial Chemotherapy of Infected Wounds.
AB - Photodynamic therapy involves delivery of a photosensitising drug that is
activated by light of a specific wavelength, resulting in generation of highly
reactive radicals. This activated species can cause destruction of targeted
cells. Application of this process for treatment of microbial infections has been
termed "photodynamic antimicrobial chemotherapy" (PACT). In the treatment of
chronic wounds, the delivery of photosensitising agents is often impeded by the
presence of a thick hyperkeratotic/necrotic tissue layer, reducing their
therapeutic efficacy. Microneedles (MNs) are an emerging drug delivery technology
that have been demonstrated to successfully penetrate the outer layers of the
skin, whilst minimising damage to skin barrier function. Delivering
photosensitising drugs using this platform has been demonstrated to have several
advantages over conventional photodynamic therapy, such as, painless application,
reduced erythema, enhanced cosmetic results and improved intradermal delivery.
The aim of this study was to physically characterise dissolving MNs loaded with
the photosensitising agent, methylene blue and assess their photodynamic
antimicrobial activity. Dissolving MNs were fabricated from aqueous blends of
Gantrez((r)) AN-139 co-polymer containing varying loadings of methylene blue. A
height reduction of 29.8% was observed for MNs prepared from blends containing
0.5% w/w methylene blue following application of a total force of 70.56 N/array.
A previously validated insertion test was used to assess the effect of drug
loading on MN insertion into a wound model. Staphylococcus aureus, Escherichia
coli and Candida albicans biofilms were incubated with various methylene blue
concentrations within the range delivered by MNs in vitro (0.1-2.5 mg/mL) and
either irradiated at 635 nm using a Paterson Lamp or subjected to a dark period.
Microbial susceptibility to PACT was determined by assessing the total viable
count. Kill rates of >96%, were achieved for S. aureus and >99% for E. coli and
C. albicans with the combination of PACT and methylene blue concentrations
between 0.1 and 2.5 mg/mL. A reduction in the colony count was also observed when
incorporating the photosensitiser without irradiation, this reduction was more
notable in S. aureus and E. coli strains than in C. albicans.
PMID- 26426041
TI - Anti-Tumor Effect of Steamed Codonopsis lanceolata in H22 Tumor-Bearing Mice and
Its Possible Mechanism.
AB - Although previous studies confirmed that steaming and the fermentation process
could significantly improve the cognitive-enhancement and neuroprotective effects
of Codonopsis lanceolata, the anti-tumor efficacy of steamed C. lanceolata (SCL)
and what mechanisms are involved remain largely unknown. The present study was
designed to evaluate the anti-tumor effect in vivo of SCL in H22 tumor-bearing
mice. The results clearly indicated that SCL could not only inhibit the tumor
growth, but also prolong the survival time of H22 tumor-bearing mice. Besides,
the serum levels of cytokines, such as interferon gamma (IFN-gamma), tumor
necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-2 (IL-2),
were enhanced by SCL administration. The observations of Hoechst 33258 staining
demonstrated that SCL was able to induce tumor cell apoptosis. Finally,
immunohistochemical analysis revealed that SCL treatment significantly increased
Bax expression and decreased Bcl-2 and vascular endothelial growth factor (VEGF)
expression of H22 tumor tissues in a dose-dependent manner. Moreover, LC/MS
analysis of SCL indicated that it mainly contained lobetyolin and six saponins.
Taken all together, the findings in the present study clearly demonstrated that
SCL inhibited the H22 tumor growth in vivo at least partly via improving the
immune functions, inducing apoptosis and inhibiting angiogenesis.
PMID- 26426042
TI - Total and Differential Phylloquinone (Vitamin K1) Intakes of Preterm Infants from
All Sources during the Neonatal Period.
AB - All newborns require phylloquinone after birth to prevent vitamin K deficiency
bleeding. Babies born prematurely may be at particular risk of deficiency without
adequate supplementation during infancy. The main sources of phylloquinone in
preterm babies during the neonatal period are the prophylactic dose of
phylloquinone given at birth, and that derived from parenteral and/or enteral
feeding. This observational study formed part of a prospective, multicentre,
randomised, controlled trial that examined the vitamin K status of preterm
infants after random allocation to one of three phylloquinone prophylactic
regimens at birth (0.5 or 0.2 mg intramuscularly or 0.2 mg intravenously). In
this nutritional sub-study we quantified the proportional and total phylloquinone
intakes of preterm infants within the neonatal period from all sources. Almost
all infants had average daily phylloquinone intakes that were in excess of the
currently recommended amounts. In infants who did not receive parenteral
nutrition, the bolus dose of phylloquinone given at birth was the major source of
phylloquinone intake, whereas in infants who received parenteral nutrition, the
intake from the parenteral preparation exceeded that from the bolus dose by a
ratio of approximately 3:1. Our study supports the concern of others that preterm
infants who receive current parenteral nutrition formulations may be receiving
excessive vitamin K.
PMID- 26426043
TI - Body Mass Index and Risk of Gallbladder Cancer: Systematic Review and Meta
Analysis of Observational Studies.
AB - OBJECTIVES: To provide a quantitative assessment of the association between
excess body weight, interpreted as increased body mass index (BMI), and the risk
of gallbladder cancer (GBC). METHODS: We identified eligible studies in Medline
and EMBASE up to 1 February 2015, and reference lists of retrieved articles.
Summary relative risks with their 95% confidence intervals were calculated in a
random-effects model. Subgroup analyses were performed according to study design,
gender, geographic location, ascertainment of exposure and adjustment for
confounders. RESUITS: A total of 12 cohort studies and 8 case-control studies
were included in the meta-analysis. Overall, compared with "normal" weight, the
summary relative risks of GBC were 1.14 (95% CI, 1.04-1.25) for overweight
individuals (BMI 25-30 kg/m2) and 1.56 (95% CI, 1.41-1.73) for obese individuals
(BMI > 30 kg/m2). Obese women had a higher risk of GBC than men did (women: SRRs
1.67, 95% CI 1.38-2.02; men: SRRs 1.42, 95% CI 1.21-1.66), and there was
significant association between overweight and GBC risk in women (SRRs 1.26, 95%
CI 1.13-1.40), but not in men (SRRs 1.06, 95% CI 0.94-1.20). CONCLUSIONS:
Findings from this meta-analysis indicate that obesity is associated with an
increased risk of GBC, especially in women. Overweight is associated with GBC
risk only in women.
PMID- 26426044
TI - Effect of Probiotic Supplement on Cytokine Levels in HIV-Infected Individuals: A
Preliminary Study.
AB - Inflammation persists in patients infected with HIV. Reduction of inflammatory
cytokines and microbial translocation might be one way that this could be
managed. PURPOSE: The anti-inflammatory properties of certain probiotic strains
prompted us to investigate whether a probiotic could reduce the inflammatory
index of HIV-infected patients. METHODS: The study involved 30 HIV+ males on
antiretroviral therapy, who were given one bottle of fermented milk Yakult
Light(r) containing Lactobacillus casei Shirota (LcS) twice a day for four weeks.
RESULTS: The probiotic LcS was associated with an increase of T lymphocytes and a
significant increase of CD56+ cells (p = 0.04). There was also a significant
decrease of mRNA levels of TGFbeta, IL-10 and IL-12 (p < 0.001) and IL-1beta
expression (p < 0.001) and an increase of serum IL-23 (p = 0.03). In addition,
decreased inflammation and cardiovascular risk were observed, as shown by a
reduction of cystatin C (p < 0.001). CONCLUSIONS: These data provide preliminary
evidence that probiotic supplementation may modulate certain immunological
parameters and some of the cytokines that were analyzed. Thus, we propose that
LcS may be an inexpensive and practical strategy to support the immune function
of HIV+ patients.
PMID- 26426046
TI - Development and Evaluation of Monoclonal Antibodies for Paxilline.
AB - Paxilline (PAX) is a tremorgenic mycotoxin that has been found in perennial
ryegrass infected with Acremonium lolii. To facilitate screening for this toxin,
four murine monoclonal antibodies (mAbs) were developed. In competitive indirect
enzyme-linked immunosorbent assays (CI-ELISAs) the concentrations of PAX required
to inhibit signal development by 50% (IC50s) ranged from 1.2 to 2.5 ng/mL. One
mAb (2-9) was applied to the detection of PAX in maize silage. The assay was
sensitive to the effects of solvents, with 5% acetonitrile or 20% methanol
causing a two-fold or greater increase in IC50. For analysis of silage samples,
extracts were cleaned up by adsorbing potential matrix interferences onto a solid
phase extraction column. The non-retained extract was then diluted with buffer to
reduce solvent content prior to assay. Using this method, the limit of detection
for PAX in dried silage was 15 ug/kg and the limit of quantification was 90
ug/kg. Recovery from samples spiked over the range of 100 to 1000 ug/kg averaged
106% +/- 18%. The assay was applied to 86 maize silage samples, with many having
detectable, but none having quantifiable, levels of PAX. The results suggest the
CI-ELISA can be applied as a sensitive technique for the screening of PAX in
maize silage.
PMID- 26426045
TI - Gut Function-Enhancing Properties and Metabolic Effects of Dietary Indigestible
Sugars in Rodents and Rabbits.
AB - Indigestible sugars (iS) have received particular interest in food and nutrition
research due to their prebiotic properties and other health benefits in humans
and animals. The main aim of this review article is to summarize the current
knowledge regarding digestive and health-enhancing properties of iS such as sugar
alcohols, oligosacharides, and polysaccharides, in rodents and rabbits. Besides
ameliorating gut health, iS ingestion also elicits laxative effects and stimulate
intestinal permeability and fluid secretions, thereby shortening digesta transit
time and increasing stool mass and quality. In rodents and rabbits, as hindgut
fermenters, consumption of iS leads to an improved nutrient digestibility, too.
Cecal fermentation of iS reduces luminal pH and extends wall tissue facilitating
absorption of key dietary minerals across hindgut. The microbial fermentation of
iS also enhances excessive blood nitrogen (N) flowing into the cecum to be used
as N source for bacterial growth, enhancing N retention in cecotrophic animals.
This review also highlights the impact of iS on improving lipid metabolism,
mainly by lowering cholesterol and triglycerides levels in the blood. The paper
serves as an index of the current knowledge of iS effects in rodents and rabbits
and also identifies gaps of knowledge that need to be addressed by future
research.
PMID- 26426048
TI - Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of
Chronic Kidney Disease and during Hemodialysis.
AB - As protein binding of uremic toxins is not well understood, neither in chronic
kidney disease (CKD) progression, nor during a hemodialysis (HD) session, we
studied protein binding in two cross-sectional studies. Ninety-five CKD 2 to 5
patients and ten stable hemodialysis patients were included. Blood samples were
taken either during the routine ambulatory visit (CKD patients) or from blood
inlet and outlet line during dialysis (HD patients). Total (CT) and free
concentrations were determined of p-cresylglucuronide (pCG), hippuric acid (HA),
indole-3-acetic acid (IAA), indoxyl sulfate (IS) and p-cresylsulfate (pCS), and
their percentage protein binding (%PB) was calculated. In CKD patients, %PB/CT
resulted in a positive correlation (all p < 0.001) with renal function for all
five uremic toxins. In HD patients, %PB was increased after 120 min of dialysis
for HA and at the dialysis end for the stronger (IAA) and the highly-bound (IS
and pCS) solutes. During one passage through the dialyzer at 120 min, %PB was
increased for HA (borderline), IAA, IS and pCS. These findings explain why
protein-bound solutes are difficult to remove by dialysis: a combination of the
fact that (i) only the free fraction can pass the filter and (ii) the
equilibrium, as it was pre-dialysis, cannot be restored during the dialysis
session, as it is continuously disturbed.
PMID- 26426049
TI - Detection of Dinophysistoxin-1 in Clonal Culture of Marine Dinoflagellate
Prorocentrum foraminosum (Faust M.A., 1993) from the Sea of Japan.
AB - For the first time the presence of dinophysistoxin-1 (DTX-1) in a culture of
Prorocentrum foraminosum was revealed in cells and in the culture medium. The
clone was isolated from coastal waters of the Sea of Japan and identified by
molecular analyses of SSU and D1/D2 regions of LSU rDNA. The concentration of DTX
1 in cells was 8.4 +/- 2.5 pg/cell and, in cell-free media, 27.9 +/- 14.7 ug/L.
The toxin presence was confirmed by HPLC with high-resolution tandem mass
spectrometry.
PMID- 26426047
TI - Conotoxin Interactions with alpha9alpha10-nAChRs: Is the alpha9alpha10-Nicotinic
Acetylcholine Receptor an Important Therapeutic Target for Pain Management?
AB - The alpha9alpha10-nicotinic acetylcholine receptor (nAChR) has been implicated in
pain and has been proposed to be a novel target for analgesics. However, the
evidence to support the involvement of the alpha9alpha10-nAChR in pain is
conflicted. This receptor was first implicated in pain with the characterisation
of conotoxin Vc1.1, which is highly selective for alpha9alpha10-nAChRs and is an
efficacious analgesic in chronic pain models with restorative capacities and no
reported side effects. Numerous other analgesic conotoxin and non-conotoxin
molecules have been subsequently characterised that also inhibit alpha9alpha10
nAChRs. However, there is evidence that alpha9alpha10-nAChR inhibition is neither
necessary nor sufficient for analgesia. alpha9alpha10-nAChR-inhibiting analogues
of Vc1.1 have no analgesic effects. Genetically-modified alpha9-nAChR knockout
mice have a phenotype that is markedly different from the analgesic profile of
Vc1.1 and similar conotoxins, suggesting that the conotoxin effects are largely
independent of alpha9alpha10-nAChRs. Furthermore, an alternative mechanism of
analgesia by Vc1.1 and other similar conotoxins involving non-canonical coupling
of GABAB receptors to voltage-gated calcium channels is known. Additional
incongruities regarding alpha9alpha10-nAChRs in analgesia are discussed. A more
comprehensive characterisation of the role of alpha9alpha10-nAChRs in pain is
crucial for understanding the analgesic action of conotoxins and for improved
drug design.
PMID- 26426050
TI - Passive Immunotherapy Protects against Enteric Invasion and Lethal Sepsis in a
Murine Model of Gastrointestinal Anthrax.
AB - The principal portal for anthrax infection in natural animal outbreaks is the
digestive tract. Enteric exposure to anthrax, which is difficult to detect or
prevent in a timely manner, could be exploited as an act of terror through
contamination of human or animal food. Our group has developed a novel animal
model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and
experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne
strain) administered to A/J mice (a complement-deficient strain) by oral gavage.
We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that
neutralizes the protective antigen (PA) component of B. anthracis lethal toxin
(LT) and edema toxin (ET) could be an effective treatment. Although the efficacy
of this anti-anthrax PA mAb has been shown in animal models of inhalational
anthrax, its activity in GI infection had not yet been ascertained. We hereby
demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at
the same time as gastrointestinal exposure to B. anthracis, prevents lethal
sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in
treatment still greatly reduces mortality following exposure (65%). Moreover,
passive immunotherapy protects against enteric invasion, associated mucosal
injury and subsequent dissemination by gastrointestinal B. anthracis, indicating
that it acts to prevent the initial stages of infection. * Expired raxibacumab
being cycled off the Strategic National Stockpile; biological activity confirmed
by in vitro assay.
PMID- 26426051
TI - Study of Adsorption and Flocculation Properties of Natural Clays to Remove
Prorocentrum lima.
AB - High accumulations of phytoplankton species that produce toxins are referred to
as harmful algal blooms (HABs). HABs represent one of the most important sources
of contamination in marine environments, as well as a serious threat to public
health, fisheries, aquaculture-based industries, and tourism. Therefore, methods
effectively controlling HABs with minimal impact on marine ecology are required.
Marine dinoflagellates of the genera Dinophysis and Prorocentrum are
representative producers of okadaic acid (OA) and dinophysistoxins responsible
for the diarrhetic shellfish poisoning (DSP) which is a human intoxication caused
by the consumption of shellfish that bioaccumulate those toxins. In this work we
explore the use of natural clay for removing Prorocentrum lima. We evaluate the
adsorption properties of clays in seawater containing the dinoflagellates. The
experimental results confirmed the cell removal through the flocculation of algal
and mineral particles leading to the formation of aggregates, which rapidly
settle and further entrain cells during their descent. Moreover, the microscopy
images of the samples enable one to observe the clays in aggregates of two or
more cells where the mineral particles were bound to the outer membranes of the
dinoflagellates. Therefore, this preliminary data offers promising results to use
these clays for the mitigation of HABs.
PMID- 26426053
TI - Clinical Implications of Hedgehog Pathway Signaling in Prostate Cancer.
AB - Activity in the Hedgehog pathway, which regulates GLI-mediated transcription, is
important in organogenesis and stem cell regulation in self-renewing organs, but
is pathologically elevated in many human malignancies. Mutations leading to
constitutive activation of the pathway have been implicated in medulloblastoma
and basal cell carcinoma, and inhibition of the pathway has demonstrated clinical
responses leading to the approval of the Smoothened inhibitor, vismodegib, for
the treatment of advanced basal cell carcinoma. Aberrant Hedgehog pathway
signaling has also been noted in prostate cancer with evidence suggesting that it
may render prostate epithelial cells tumorigenic, drive the epithelial-to
mesenchymal transition, and contribute towards the development of castration
resistance through autocrine and paracrine signaling within the tumor
microenvironment and cross-talk with the androgen pathway. In addition, there are
emerging clinical data suggesting that inhibition of the Hedgehog pathway may be
effective in the treatment of recurrent and metastatic prostate cancer. Here we
will review these data and highlight areas of active clinical research as they
relate to Hedgehog pathway inhibition in prostate cancer.
PMID- 26426052
TI - Histone Modifications, Modifiers and Readers in Melanoma Resistance to Targeted
and Immune Therapy.
AB - The treatment of melanoma has been revolutionized by new therapies targeting MAPK
signaling or the immune system. Unfortunately these therapies are hindered by
either primary resistance or the development of acquired resistance. Resistance
mechanisms involving somatic mutations in genes associated with resistance have
been identified in some cases of melanoma, however, the cause of resistance
remains largely unexplained in other cases. The importance of epigenetic factors
targeting histones and histone modifiers in driving the behavior of melanoma is
only starting to be unraveled and provides significant opportunity to combat the
problems of therapy resistance. There is also an increasing ability to target
these epigenetic changes with new drugs that inhibit these modifications to
either prevent or overcome resistance to both MAPK inhibitors and immunotherapy.
This review focuses on changes in histones, histone reader proteins and histone
positioning, which can mediate resistance to new therapeutics and that can be
targeted for future therapies.
PMID- 26426054
TI - The Mesothelial Origin of Carcinoma Associated-Fibroblasts in Peritoneal
Metastasis.
AB - Solid tumors are complex and unstructured organs that, in addition to cancer
cells, also contain other cell types. Carcinoma-associated fibroblasts (CAFs)
represent an important population in the tumor microenviroment and participate in
several stages of tumor progression, including cancer cell migration/invasion and
metastasis. During peritoneal metastasis, cancer cells detach from the primary
tumor, such as ovarian or gastrointestinal, disseminate through the peritoneal
fluid and colonize the peritoneum. Tumor cells metastasize by attaching to and
invading through the mesothelial cell (MC) monolayer that lines the peritoneal
cavity, then colonizing the submesothelial compact zone where CAFs accumulate.
CAFs may derive from different sources depending on the surrounding metastatic
niche. In peritoneal metastasis, a sizeable subpopulation of CAFs originates from
MCs through a mesothelial-to-mesenchymal transition (MMT), which promotes
adhesion, invasion, vascularization and subsequent tumor growth. The
bidirectional communication between cancer cells and MC-derived CAFs via
secretion of a wide range of cytokines, growth factors and extracellular matrix
components seems to be crucial for the establishment and progression of the
metastasis in the peritoneum. This manuscript provides a comprehensive review of
novel advances in understanding how peritoneal CAFs provide cancer cells with a
supportive microenvironment, as well as the development of future therapeutic
approaches by interfering with the MMT in the peritoneum.
PMID- 26426055
TI - Intracellular Mono-ADP-Ribosylation in Signaling and Disease.
AB - A key process in the regulation of protein activities and thus cellular signaling
pathways is the modification of proteins by post-translational mechanisms.
Knowledge about the enzymes (writers and erasers) that attach and remove post
translational modifications, the targets that are modified and the functional
consequences elicited by specific modifications, is crucial for understanding
cell biological processes. Moreover detailed knowledge about these mechanisms and
pathways helps to elucidate the molecular causes of various diseases and in
defining potential targets for therapeutic approaches. Intracellular adenosine
diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide
(NAD+)-dependent modification of proteins with ADP-ribose and is catalyzed by
enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as
PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation
is relatively well understood with inhibitors being used as anti-cancer agents.
However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are
restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and
erasers of intracellular mono-ADP-ribosylation have been identified only
recently, it is becoming more and more evident that this reversible post
translational modification is capable of modulating key intracellular processes
and signaling pathways. These include signal transduction mechanisms, stress
pathways associated with the endoplasmic reticulum and stress granules, and
chromatin-associated processes such as transcription and DNA repair. We
hypothesize that mono-ADP-ribosylation controls, through these different
pathways, the development of cancer and infectious diseases.
PMID- 26426057
TI - Non-Conserved Residues in Clostridium acetobutylicum tRNA(Ala) Contribute to tRNA
Tuning for Efficient Antitermination of the alaS T Box Riboswitch.
AB - The T box riboswitch regulates expression of amino acid-related genes in Gram
positive bacteria by monitoring the aminoacylation status of a specific tRNA, the
binding of which affects the folding of the riboswitch into mutually exclusive
terminator or antiterminator structures. Two main pairing interactions between
the tRNA and the leader RNA have been demonstrated to be necessary, but not
sufficient, for efficient antitermination. In this study, we used the Clostridium
acetobutylicum alaS gene, which encodes alanyl-tRNA synthetase, to investigate
the specificity of the tRNA response. We show that the homologous C.
acetobutylicum tRNA(Ala) directs antitermination of the C. acetobutylicum alaS
gene in vitro, but the heterologous Bacillus subtilis tRNA(Ala) (with the same
anticodon and acceptor end) does not. Base substitutions at positions that vary
between these two tRNAs revealed synergistic and antagonistic effects. Variation
occurs primarily at positions that are not conserved in tRNA(Ala) species, which
indicates that these non-conserved residues contribute to optimal antitermination
of the homologous alaS gene. This study suggests that elements in tRNA(Ala) may
have coevolved with the homologous alaS T box leader RNA for efficient
antitermination.
PMID- 26426056
TI - Epigenetic Therapy for Solid Tumors: Highlighting the Impact of Tumor Hypoxia.
AB - In the last few decades, epigenetics has emerged as an exciting new field in
development and disease, with a more recent focus towards cancer. Epigenetics has
classically referred to heritable patterns of gene expression, primarily mediated
through DNA methylation patterns. More recently, it has come to include the
reversible chemical modification of histones and DNA that dictate gene expression
patterns. Both the epigenetic up-regulation of oncogenes and downregulation of
tumor suppressors have been shown to drive tumor development. Current clinical
trials for cancer therapy include pharmacological inhibition of DNA methylation
and histone deacetylation, with the aim of reversing these cancer-promoting
epigenetic changes. However, the DNA methyltransferase and histone deacetylase
inhibitors have met with less than promising results in the treatment of solid
tumors. Regions of hypoxia are a common occurrence in solid tumors. Tumor hypoxia
is associated with increased aggressiveness and therapy resistance, and
importantly, hypoxic tumor cells have a distinct epigenetic profile. In this
review, we provide a summary of the recent clinical trials using epigenetic drugs
in solid tumors, discuss the hypoxia-induced epigenetic changes and highlight the
importance of testing the epigenetic drugs for efficacy against the most
aggressive hypoxic fraction of the tumor in future preclinical testing.
PMID- 26426058
TI - The Scalp Confounds Near-Infrared Signal from Rat Brain Following Innocuous and
Noxious Stimulation.
AB - Functional near-infrared imaging (fNIRI) is a non-invasive, low-cost and highly
portable technique for assessing brain activity and functions. Both clinical and
experimental evidence suggest that fNIRI is able to assess brain activity at
associated regions during pain processing, indicating a strong possibility of
using fNIRI-derived brain activity pattern as a biomarker for pain. However, it
remains unclear how, especially in small animals, the scalp influences fNIRI
signal in pain processing. Previously, we have shown that the use of a multi
channel system improves the spatial resolution of fNIRI in rats (without the
scalp) during pain processing. Our current work is to investigate a scalp effect
by comparing with new data from rats with the scalp during innocuous or noxious
stimulation (n = 6). Results showed remarkable stimulus-dependent differences
between the no-scalp and intact-scalp groups. In conclusion, the scalp confounded
the fNIRI signal in pain processing likely via an autonomic mechanism; the scalp
effect should be a critical factor in image reconstruction and data
interpretation.
PMID- 26426059
TI - Hemodynamic and Light-Scattering Changes of Rat Spinal Cord and Primary
Somatosensory Cortex in Response to Innocuous and Noxious Stimuli.
AB - Neuroimaging technologies with an exceptional spatial resolution and
noninvasiveness have become a powerful tool for assessing neural activity in both
animals and humans. However, the effectiveness of neuroimaging for pain remains
unclear partly because the neurovascular coupling during pain processing is not
completely characterized. Our current work aims to unravel patterns of
neurovascular parameters in pain processing. A novel fiber-optic method was used
to acquire absolute values of regional oxy- (HbO) and deoxy-hemoglobin
concentrations, oxygen saturation rates (SO2), and the light-scattering
coefficients from the spinal cord and primary somatosensory cortex (SI) in 10
rats. Brief mechanical and electrical stimuli (ranging from innocuous to noxious
intensities) as well as a long-lasting noxious stimulus (formalin injection) were
applied to the hindlimb under pentobarbital anesthesia. Interhemispheric
comparisons in the spinal cord and SI were used to confirm functional activation
during sensory processing. We found that all neurovascular parameters showed
stimulation-induced changes; however, patterns of changes varied with regions and
stimuli. Particularly, transient increases in HbO and SO2 were more reliably
attributed to brief stimuli, whereas a sustained decrease in SO2 was more
reliably attributed to formalin. Only the ipsilateral SI showed delayed responses
to brief stimuli. In conclusion, innocuous and noxious stimuli induced
significant neurovascular responses at critical centers (e.g., the spinal cord
and SI) along the somatosensory pathway; however, there was no single response
pattern (as measured by amplitude, duration, lateralization, decrease or
increase) that was able to consistently differentiate noxious stimuli. Our
results strongly suggested that the neurovascular response patterns differ
between brief and long-lasting noxious stimuli, and can also differ between the
spinal cord and SI. Therefore, a use of multiple-parameter strategy tailored by
stimulus modality (brief or long-lasting) as well as region-dependent
characteristics may be more effective in detecting pain using neuroimaging
technologies.
PMID- 26426060
TI - Micelle-Based Adjuvants for Subunit Vaccine Delivery.
AB - In the development of subunit vaccines with purified or recombinant antigens for
cancer and infectious diseases, the design of improved and safe adjuvants able to
efficiently target the antigen presenting cells, such as dendritic cells,
represents a crucial challenge. Nanoparticle-based antigen delivery systems have
been identified as an innovative strategy to improve the efficacy of subunit
vaccines. Among them, self-assembled micellar nanoparticles from amphiphilic
(macro)molecules have recently emerged as promising candidates. In this short
review, we report on the recent research findings highlighting the versatility
and potential of such systems in vaccine delivery.
PMID- 26426061
TI - The Effect of the Nonlinearity of the Response of Lipid Membranes to Voltage
Perturbations on the Interpretation of Their Electrical Properties. A New
Theoretical Description.
AB - Our understanding of the electrical properties of cell membranes is derived from
experiments where the membrane is exposed to a perturbation (in the form of a
time-dependent voltage or current change) and information is extracted from the
measured output. The interpretation of such electrical recordings consists in
finding an electronic equivalent that would show the same or similar response as
the biological system. In general, however, there is no unique circuit
configuration, which can explain a single electrical recording and the choice of
an electric model for a biological system is based on complementary information
(most commonly structural information) of the system investigated. Most of the
electrophysiological data on cell membranes address the functional role of
protein channels while assuming that the lipid matrix is an insulator with
constant capacitance. However, close to their melting transition the lipid
bilayers are no inert insulators. Their conductivity and their capacitance are
nonlinear functions of both voltage, area and volume density. This has to be
considered when interpreting electrical data. Here we show how electric data
commonly interpreted as gating currents of proteins and inductance can be
explained by the nonlinear dynamics of the lipid matrix itself.
PMID- 26426062
TI - On the Recent Use of Membrane Technology for Olive Mill Wastewater Purification.
AB - Many reclamation treatments as well as integrated processes for the purification
of olive mill wastewaters (OMW) have already been proposed and developed but not
led to completely satisfactory results, principally due to complexity or cost
ineffectiveness. The olive oil industry in its current status, composed of little
and dispersed factories, cannot stand such high costs. Moreover, these treatments
are not able to abate the high concentration of dissolved inorganic matter
present in these highly polluted effluents. In the present work, a review on the
actual state of the art concerning the treatment and disposal of OMW by membranes
is addressed, comprising microfiltration (MF), ultrafiltration (UF),
nanofiltration (NF), and reverse osmosis (RO), as well as membrane bioreactors
(MBR) and non-conventional membrane processes such as vacuum distillation (VD),
osmotic distillation (OD) and forward osmosis (FO). Membrane processes are
becoming extensively used to replace many conventional processes in the
purification of water and groundwater as well as in the reclamation of wastewater
streams of very diverse sources, such as those generated by agro-industrial
activities. Moreover, a brief insight into inhibition and control of fouling by
properly-tailored pretreatment processes upstream the membrane operation and the
use of the critical and threshold flux theories is provided.
PMID- 26426063
TI - Strong Static Magnetic Fields Increase the Gel Signal in Partially Hydrated
DPPC/DMPC Membranes.
AB - NIt was recently reported that static magnetic fields increase lipid order in the
hydrophobic membrane core of dehydrated native plant plasma membranes [Poinapen,
Soft Matter 9:6804-6813, 2013]. As plasma membranes are multicomponent, highly
complex structures, in order to elucidate the origin of this effect, we prepared
model membranes consisting of a lipid species with low and high melting
temperature. By controlling the temperature, bilayers coexisting of small gel and
fluid domains were prepared as a basic model for the plasma membrane core. We
studied molecular order in mixed lipid membranes made of dimyristoyl-sn-glycero-3
phosphocholine (DMPC) and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) using
neutron diffraction in the presence of strong static magnetic fields up to 3.5 T.
The contribution of the hydrophobic membrane core was highlighted through
deuterium labeling the lipid acyl chains. There was no observable effect on lipid
organization in fluid or gel domains at high hydration of the membranes. However,
lipid order was found to be enhanced at a reduced relative humidity of 43%: a
magnetic field of 3.5 T led to an increase of the gel signal in the diffraction
patterns of 5%. While all biological materials have weak diamagnetic properties,
the corresponding energy is too small to compete against thermal disorder or
viscous effects in the case of lipid molecules. We tentatively propose that the
interaction between the fatty acid chains' electric moment and the external
magnetic field is driving the lipid tails in the hydrophobic membrane core into a
better ordered state.
PMID- 26426064
TI - Regulation of the Target of Rapamycin and Other Phosphatidylinositol 3-Kinase
Related Kinases by Membrane Targeting.
AB - Phosphatidylinositol 3-kinase-related kinases (PIKKs) play vital roles in the
regulation of cell growth, proliferation, survival, and consequently metabolism,
as well as in the cellular response to stresses such as ionizing radiation or
redox changes. In humans six family members are known to date, namely
mammalian/mechanistic target of rapamycin (mTOR), ataxia-telangiectasia mutated
(ATM), ataxia- and Rad3-related (ATR), DNA-dependent protein kinase catalytic
subunit (DNA-PKcs), suppressor of morphogenesis in genitalia-1 (SMG-1), and
transformation/transcription domain-associated protein (TRRAP). All fulfill
rather diverse functions and most of them have been detected in different
cellular compartments including various cellular membranes. It has been suggested
that the regulation of the localization of signaling proteins allows for
generating a locally specific output. Moreover, spatial partitioning is expected
to improve the reliability of biochemical signaling. Since these assumptions may
also be true for the regulation of PIKK function, the current knowledge about the
regulation of the localization of PIKKs at different cellular (membrane)
compartments by a network of interactions is reviewed. Membrane targeting can
involve direct lipid-/membrane interactions as well as interactions with membrane
anchored regulatory proteins, such as, for example, small GTPases, or a
combination of both.
PMID- 26426066
TI - T Cells in Fish.
AB - Cartilaginous and bony fish are the most primitive vertebrates with a thymus, and
possess T cells equivalent to those in mammals. There are a number of studies in
fish demonstrating that the thymus is the essential organ for development of T
lymphocytes from early thymocyte progenitors to functionally competent T cells. A
high number of T cells in the intestine and gills has been reported in several
fish species. Involvement of CD4+ and CD8alpha+ T cells in allograft rejection
and graft-versus-host reaction (GVHR) has been demonstrated using monoclonal
antibodies. Conservation of CD4+ helper T cell functions among teleost fishes has
been suggested in a number studies employing mixed leukocyte culture (MLC) and
hapten/carrier effect. Alloantigen- and virus-specific cytotoxicity has also been
demonstrated in ginbuna and rainbow trout. Furthermore, the important role of
cell-mediated immunity rather than humoral immunity has been reported in the
protection against intracellular bacterial infection. Recently, the direct
antibacterial activity of CD8alpha+, CD4+ T-cells and sIgM+ cells in fish has
been reported. In this review, we summarize the recent progress in T cell
research focusing on the tissue distribution and function of fish T cells.
PMID- 26426065
TI - Antimicrobial Peptides as Mediators of Innate Immunity in Teleosts.
AB - Antimicrobial peptides (AMPs) have been identified throughout the metazoa
suggesting their evolutionarily conserved nature and their presence in teleosts
is no exception. AMPs are short (18-46 amino acids), usually cationic,
amphipathic peptides. While AMPs are diverse in amino acid sequence, with no two
AMPs being identical, they collectively appear to have conserved functions in the
innate immunity of animals towards the pathogens they encounter in their
environment. Fish AMPs are upregulated in response to pathogens and appear to
have direct broad-spectrum antimicrobial activity towards both human and fish
pathogens. However, an emerging role for AMPs as immunomodulatory molecules has
become apparent-the ability of AMPs to activate the innate immune system sheds
light onto the multifaceted capacity of these small peptides to combat pathogens
through direct and indirect means. Herein, this review focuses on the role of
teleost AMPs as modulators of the innate immune system and their regulation in
response to pathogens or other exogenous molecules. The capacity to regulate AMP
expression by exogenous factors may prove useful in modulating AMP expression in
fish to prevent disease, particularly in aquaculture settings where crowded
conditions and environmental stress pre-dispose these fish to infection.
PMID- 26426069
TI - Incidence of dentinal defects after preparation of severely curved root canals
using the Reciproc single-file system with and without prior creation of a glide
path.
AB - AIM: To investigate the incidence of dentinal defects after preparation of
severely curved root canals using the Reciproc single-file system with and
without prior creation of a glide path. METHODOLOGY: Mesial roots from extracted
mandibular first molars were collected and scanned with CBCT to assess the
morphology of the root canal systems. Three groups of 20 anatomically comparable
specimens were generated. The control group was left unprepared, whilst the
experimental groups were prepared with Reciproc R25 with and without a glide path
(groups RG and R, respectively). Roots were then sectioned perpendicular to the
long axis at 2, 4, 6, 8 and 10 mm from the apex, and coloured photographs of the
sections at 40* were obtained. Two blinded examiners registered the presence of
dentinal defects twice at 2-week interval. Data were statistically analysed using
the Fisher exact and Cochran's Q tests. RESULTS: No defects were observed in the
control group. The overall incidence of dentinal defects was 26% in group R and
24% in group RG, with no significant differences between them (P > 0.05).
Dentinal defects occurred significantly more often in the middle and coronal
thirds compared to the apical third of the canals (P < 0.05). CONCLUSIONS: Prior
preparation of a glide path had no impact on the incidence of dentinal defects
when using Reciproc files.
PMID- 26426070
TI - LM-CMA: An Alternative to L-BFGS for Large-Scale Black Box Optimization.
AB - Limited-memory BFGS (L-BFGS; Liu and Nocedal, 1989 ) is often considered to be
the method of choice for continuous optimization when first- or second-order
information is available. However, the use of L-BFGS can be complicated in a
black box scenario where gradient information is not available and therefore
should be numerically estimated. The accuracy of this estimation, obtained by
finite difference methods, is often problem-dependent and may lead to premature
convergence of the algorithm. This article demonstrates an alternative to L-BFGS,
the limited memory covariance matrix adaptation evolution strategy (LM-CMA)
proposed by Loshchilov ( 2014 ). LM-CMA is a stochastic derivative-free algorithm
for numerical optimization of nonlinear, nonconvex optimization problems.
Inspired by L-BFGS, LM-CMA samples candidate solutions according to a covariance
matrix reproduced from m direction vectors selected during the optimization
process. The decomposition of the covariance matrix into Cholesky factors allows
reducing the memory complexity to [Formula: see text], where n is the number of
decision variables. The time complexity of sampling one candidate solution is
also [Formula: see text] but scales as only about 25 scalar-vector
multiplications in practice. The algorithm has an important property of
invariance with respect to strictly increasing transformations of the objective
function; such transformations do not compromise its ability to approach the
optimum. LM-CMA outperforms the original CMA-ES and its large-scale versions on
nonseparable ill-conditioned problems with a factor increasing with problem
dimension. Invariance properties of the algorithm do not prevent it from
demonstrating a comparable performance to L-BFGS on nontrivial large-scale smooth
and nonsmooth optimization problems.
PMID- 26426067
TI - Using Gene Essentiality and Synthetic Lethality Information to Correct Yeast and
CHO Cell Genome-Scale Models.
AB - Essentiality (ES) and Synthetic Lethality (SL) information identify combination
of genes whose deletion inhibits cell growth. This information is important for
both identifying drug targets for tumor and pathogenic bacteria suppression and
for flagging and avoiding gene deletions that are non-viable in biotechnology. In
this study, we performed a comprehensive ES and SL analysis of two important
eukaryotic models (S. cerevisiae and CHO cells) using a bilevel optimization
approach introduced earlier. Information gleaned from this study is used to
propose specific model changes to remedy inconsistent with data model
predictions. Even for the highly curated Yeast 7.11 model we identified 50
changes (metabolic and GPR) leading to the correct prediction of an additional
28% of essential genes and 36% of synthetic lethals along with a 53% reduction in
the erroneous identification of essential genes. Due to the paucity of mutant
growth phenotype data only 12 changes were made for the CHO 1.2 model leading to
an additional correctly predicted 11 essential and eight non-essential genes.
Overall, we find that CHO 1.2 was 76% less accurate than the Yeast 7.11 metabolic
model in predicting essential genes. Based on this analysis, 14 (single and
double deletion) maximally informative experiments are suggested to improve the
CHO cell model by using information from a mouse metabolic model. This analysis
demonstrates the importance of single and multiple knockout phenotypes in
assessing and improving model reconstructions. The advent of techniques such as
CRISPR opens the door for the global assessment of eukaryotic models.
PMID- 26426071
TI - Perinatal outcomes after hypertensive disorders in pregnancy in a low resource
setting.
AB - OBJECTIVE: The objective of this study was to evaluate perinatal outcomes of
pregnancies complicated by hypertensive disorders in pregnancy in an urban sub
Saharan African setting. METHODS: A prospective cohort study of 1010 women of
less than 17 weeks of gestation was conducted at two antenatal clinics in Accra,
Ghana, between July 2012 and March 2014. Information about hypertensive disorders
was available for analysis on 789 pregnancies. The main outcomes were pre-term
birth, birthweight, Apgar scores, small for gestational age and mortality.
Relative risk (RR, 95% confidence interval (CI)) for the association between
hypertensive disorders of pregnancy and perinatal outcomes was assessed using
logistic regression adjusting for potential confounders. RESULTS: A total of
88.7% of women remained normotensive, 7.5% developed pregnancy-induced
hypertension, 2.0% had chronic hypertension, and 1.7% developed (pre-)eclampsia.
No adverse effects were observed in women with pregnancy-induced hypertension.
Women with chronic hypertension were more likely to have a lower gestational age
at delivery (38.0 +/- 2.3 weeks vs. 39.0 +/- 1.9 weeks, P = 0.04) and higher risk
of pre-term delivery (aRR 4.63, 95% CI 1.35-15.91). Women with pre-eclampsia had
emergency Caesarean section significantly more often (88.9% vs. 50%, P = 0.04),
with a higher risk for low birthweight infants (aRR 7.95, 95% CI 1.41-44.80) and
a higher risk of neonatal death (aRR 18.41, 95% CI 1.20-283.22). CONCLUSION:
Comparable to high-income countries, in Accra hypertensive disorders during
pregnancy were associated with increased risk of adverse perinatal outcomes
necessitating maternal and newborn care.
PMID- 26426068
TI - Impact of Alcohol on Glycemic Control and Insulin Action.
AB - Alcohol has profound effects on tissue and whole-body fuel metabolism which
contribute to the increased morbidity and mortality in individuals with alcohol
use disorder. This review focuses on the glucose metabolic effects of alcohol,
primarily in the muscle, liver and adipose tissue, under basal postabsorptive
conditions and in response to insulin stimulation. While there is a relatively
extensive literature in this area, results are often discordant and extrapolating
between models and tissues is fraught with uncertainty. Comparisons between data
generated in experimental cell and animals systems will be contrasted with that
obtained from human subjects as often times results differ. Further, the
nutritional status is also an important component of the sometimes divergent
findings pertaining to the effects of alcohol on the regulation of insulin and
glucose metabolism. This work is relevant as the contribution of alcohol intake
to the development or exacerbation of type 2 diabetes remains ill-defined and a
multi-systems approach is likely needed as both alcohol and diabetes affect
multiple targets within the body.
PMID- 26426072
TI - The Network for Evaluation of One Health: evidence-based added value of One
Health.
PMID- 26426073
TI - A conversation with Helen Hobbs.
PMID- 26426074
TI - Rescuing the physician-scientist workforce: the time for action is now.
AB - The 2014 NIH Physician-Scientist Workforce (PSW) Working Group report identified
distressing trends among the small proportion of physicians who consider research
to be their primary occupation. If unchecked, these trends will lead to a steep
decline in the size of the workforce. They include high rates of attrition among
young investigators, failure to maintain a robust and diverse pipeline, and a
marked increase in the average age of physician-scientists, as older
investigators have chosen to continue working and too few younger investigators
have entered the workforce to replace them when they eventually retire. While the
policy debates continue, here we propose four actions that can be implemented
now. These include applying lessons from the MD-PhD training experience to
postgraduate training, shortening the time to independence by at least 5 years,
achieving greater diversity and numbers in training programs, and establishing
Physician-Scientist Career Development offices at medical centers and
universities. Rather than waiting for the federal government to solve our
problems, we urge the academic community to address these goals by partnering
with the NIH and national clinical specialty and medical organizations.
PMID- 26426075
TI - Proof-of-principle rapid noninvasive prenatal diagnosis of autosomal recessive
founder mutations.
AB - BACKGROUND: Noninvasive prenatal testing can be used to accurately detect
chromosomal aneuploidies in circulating fetal DNA; however, the necessity of
parental haplotype construction is a primary drawback to noninvasive prenatal
diagnosis (NIPD) of monogenic disease. Family-specific haplotype assembly is
essential for accurate diagnosis of minuscule amounts of circulating cell-free
fetal DNA; however, current haplotyping techniques are too time-consuming and
laborious to be carried out within the limited time constraints of prenatal
testing, hampering practical application of NIPD in the clinic. Here, we have
addressed this pitfall and devised a universal strategy for rapid NIPD of a
prevalent mutation in the Ashkenazi Jewish (AJ) population. METHODS: Pregnant AJ
couples, carrying mutation(s) in GBA, which encodes acid beta-glucosidase, were
recruited at the SZMC Gaucher Clinic. Targeted next-generation sequencing of GBA
flanking SNPs was performed on peripheral blood samples from each couple,
relevant mutation carrier family members, and unrelated individuals who are
homozygotes for an AJ founder mutation. Allele-specific haplotypes were
constructed based on linkage, and a consensus Gaucher disease-associated founder
mutation-flanking haplotype was fine mapped. Together, these haplotypes were used
for NIPD. All test results were validated by conventional prenatal or postnatal
diagnostic methods. RESULTS: Ten parental alleles in eight unrelated fetuses were
diagnosed successfully based on the noninvasive method developed in this study.
The consensus mutation-flanking haplotype aided diagnosis for 6 of 9 founder
mutation alleles. CONCLUSIONS: The founder NIPD method developed and described
here is rapid, economical, and readily adaptable for prenatal testing of
prevalent autosomal recessive disease-causing mutations in an assortment of
worldwide populations. FUNDING: SZMC, Protalix Biotherapeutics Inc., and
Centogene AG.
PMID- 26426076
TI - IDO1 suppresses inhibitor development in hemophilia A treated with factor VIII.
AB - The development of inhibitory antibodies to factor VIII (FVIII) is a major
obstacle in using this clotting factor to treat individuals with hemophilia A.
Patients with a congenital absence of FVIII do not develop central tolerance to
FVIII, and therefore, any control of their FVIII-reactive lymphocytes relies upon
peripheral tolerance mechanisms. Indoleamine 2,3-dioxygenase 1 (IDO1) is a key
regulatory enzyme that supports Treg function and peripheral tolerance in adult
life. Here, we investigated the association between IDO1 competence and inhibitor
status by evaluating hemophilia A patients harboring F8-null mutations that were
either inhibitor negative (n = 50) or positive (n = 50). We analyzed IDO1
induction, expression, and function for any relationship with inhibitor
occurrence by multivariable logistic regression and determined that defective
TLR9-mediated activation of IDO1 induction is associated with an inhibitor
positive status. Evaluation of experimental hemophilic mouse models with or
without functional IDO1 revealed that tryptophan metabolites, which result from
IDO1 activity, prevent generation of anti-FVIII antibodies. Moreover, treatment
of hemophilic animals with a TLR9 agonist suppressed FVIII-specific B cells by a
mechanism that involves IDO1-dependent induction of Tregs. Together, these
findings indicate that strategies aimed at improving IDO1 function should be
further explored for preventing or eradicating inhibitors to therapeutically
administered FVIII protein.
PMID- 26426077
TI - Identifying local and descending inputs for primary sensory neurons.
AB - Primary pain and touch sensory neurons not only detect internal and external
sensory stimuli, but also receive inputs from other neurons. However, the
neuronal derived inputs for primary neurons have not been systematically
identified. Using a monosynaptic rabies viruses-based transneuronal tracing
method combined with sensory-specific Cre-drivers, we found that sensory neurons
receive intraganglion, intraspinal, and supraspinal inputs, the latter of which
are mainly derived from the rostroventral medulla (RVM). The viral-traced central
neurons were largely inhibitory but also consisted of some glutamatergic neurons
in the spinal cord and serotonergic neurons in the RVM. The majority of RVM
derived descending inputs were dual GABAergic and enkephalinergic (opioidergic).
These inputs projected through the dorsolateral funiculus and primarily
innervated layers I, II, and V of the dorsal horn, where pain-sensory afferents
terminate. Silencing or activation of the dual GABA/enkephalinergic RVM neurons
in adult animals substantially increased or decreased behavioral sensitivity,
respectively, to heat and mechanical stimuli. These results are consistent with
the fact that both GABA and enkephalin can exert presynaptic inhibition of the
sensory afferents. Taken together, this work provides a systematic view of and a
set of tools for examining peri- and extrasynaptic regulations of pain-afferent
transmission.
PMID- 26426078
TI - ZIC2-dependent OCT4 activation drives self-renewal of human liver cancer stem
cells.
AB - Liver cancer stem cells (CSCs) have been identified and shown to have self
renewal and differentiation properties; however, the biology of these hepatic
CSCs remains largely unknown. Here, we analyzed transcriptome gene expression
profiles of liver CSCs and non-CSCs from hepatocellular carcinoma (HCC) cells
lines and found that the transcription factor (TF) ZIC2 is highly expressed in
liver CSCs. ZIC2 was required for the self-renewal maintenance of liver CSCs, as
ZIC2 depletion reduced sphere formation and xenograft tumor growth in mice. We
determined that ZIC2 acts upstream of the TF OCT4 and that ZIC2 recruits the
nuclear remodeling factor (NURF) complex to the OCT4 promoter, thereby initiating
OCT4 activation. In HCC patients, expression levels of the NURF complex were
consistent with clinical severity and prognosis. Moreover, ZIC2 and OCT4 levels
positively correlated to the clinicopathological stages of HCC patients.
Altogether, our results indicate that levels of ZIC2, OCT4, and the NURF complex
can be detected and used for diagnosis and prognosis prediction of HCC patients.
Moreover, these factors may be potential therapeutic targets for eradicating
liver CSCs.
PMID- 26426080
TI - CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells
and defines connective tissue healing in a rodent injury model.
PMID- 26426081
TI - The tragic fate of group 3 innate lymphoid cells during HIV-1 infection.
PMID- 26426082
TI - A New Strategy to Increase Scientific Publications and Facilitate Research Uptake
in the Caribbean.
PMID- 26426079
TI - Bacterial exploitation of phosphorylcholine mimicry suppresses inflammation to
promote airway infection.
AB - Regulation of neutrophil activity is critical for immune evasion among
extracellular pathogens, yet the mechanisms by which many bacteria disrupt
phagocyte function remain unclear. Here, we have shown that the respiratory
pathogen Streptococcus pneumoniae disables neutrophils by exploiting molecular
mimicry to degrade platelet-activating factor (PAF), a host-derived inflammatory
phospholipid. Using mass spectrometry and murine upper airway infection models,
we demonstrated that phosphorylcholine (ChoP) moieties that are shared by PAF and
the bacterial cell wall allow S. pneumoniae to leverage a ChoP-remodeling enzyme
(Pce) to remove PAF from the airway. S. pneumoniae-mediated PAF deprivation
impaired viability, activation, and bactericidal capacity among responding
neutrophils. In the absence of Pce, neutrophils rapidly cleared S. pneumoniae
from the airway and impeded invasive disease and transmission between mice.
Abrogation of PAF signaling rendered Pce dispensable for S. pneumoniae
persistence, reinforcing that this enzyme deprives neutrophils of essential PAF
mediated stimulation. Accordingly, exogenous activation of neutrophils
overwhelmed Pce-mediated phagocyte disruption. Haemophilus influenzae also uses
an enzyme, GlpQ, to hydrolyze ChoP and subvert PAF function, suggesting that
mimicry-driven immune evasion is a common paradigm among respiratory pathogens.
These results identify a mechanism by which shared molecular structures enable
microbial enzymes to subvert host lipid signaling, suppress inflammation, and
ensure bacterial persistence at the mucosa.
PMID- 26426084
TI - Alexithymia in children with and without autism spectrum disorders.
AB - Alexithymia refers to pronounced difficulty in identifying and describing one's
own emotions and is associated with an externally oriented focus of thinking.
Alexithymia is known to be much more common in adults with autism spectrum
disorders (ASD) compared with the typically developing (TD) adult population.
However, we know very little about alexithymia in young children with ASD and
advancing our understanding of this topic may be of critical clinical and
translational importance. Here, we present the first study to examine alexithymia
in children with ASD. We find that alexithymia is substantially elevated in ASD
on both self- and parent-report measures. Despite both measures being sensitive
to on-average group differentiation, we find no evidence of correlation between
such measures, indicating that children and their parents may be using different
sources of information. Parent-rated alexithymia is also associated with
increasing levels of autistic traits. Discrepancy between self and other
alexithymia ratings are also associated with autistic traits, but only in ASD.
These results underscore the idea that assessing alexithymia in ASD at younger
ages may help identify important subgroups that have particular difficulties in
the domain of emotion processing. Autism Res 2016, 9: 773-780. (c) 2015
International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 26426085
TI - Boosting the sensitivity of Nd(3+)-based luminescent nanothermometers.
AB - Luminescence thermal sensing and deep-tissue imaging using nanomaterials
operating within the first biological window (ca. 700-980 nm) are of great
interest, prompted by the ever-growing demands in the fields of nanotechnology
and nanomedicine. Here, we show that (Gd1-xNdx)2O3 (x = 0.009, 0.024 and 0.049)
nanorods exhibit one of the highest thermal sensitivity and temperature
uncertainty reported so far (1.75 +/- 0.04% K(-1) and 0.14 +/- 0.05 K,
respectively) for a nanothermometer operating in the first transparent near
infrared window at temperatures in the physiological range. This sensitivity
value is achieved using a common R928 photomultiplier tube that allows defining
the thermometric parameter as the integrated intensity ratio between the (4)F5/2
> (4)I9/2 and (4)F3/2 -> (4)I9/2 transitions (with an energy difference between
the barycentres of the two transitions >1000 cm(-1)). Moreover, the measured
sensitivity is one order of magnitude higher than the values reported so far for
Nd(3+)-based nanothermometers enlarging, therefore, the potential of using Nd(3+)
ions in luminescence thermal sensing and deep-tissue imaging.
PMID- 26426083
TI - Neisseria gonorrhoeae survives within and modulates apoptosis and inflammatory
cytokine production of human macrophages.
AB - The human-adapted organism Neisseria gonorrhoeae is the causative agent of
gonorrhoea, a sexually transmitted infection. It readily colonizes the genital,
rectal and nasalpharyngeal mucosa during infection. While it is well established
that N. gonorrhoeae recruits and modulates the functions of polymorphonuclear
leukocytes during infection, how N. gonorrhoeae interacts with macrophages
present in infected tissue is not fully defined. We studied the interactions of
N. gonorrhoeae with two human monocytic cell lines, THP-1 and U937, and primary
monocytes, all differentiated into macrophages. Most engulfed bacteria were
killed in the phagolysosome, but a subset of bacteria was able to survive and
replicate inside the macrophages suggesting that those cells may be an unexplored
cellular reservoir for N. gonorrhoeae during infection. N. gonorrhoeae was able
to modulate macrophage apoptosis: N. gonorrhoeae induced apoptosis in THP-1 cells
whereas it inhibited induced apoptosis in U937 cells and primary human
macrophages. Furthermore, N. gonorrhoeae induced expression of inflammatory
cytokines in macrophages, suggesting a role for macrophages in recruiting
polymorphonuclear leukocytes to the site of infection. These results indicate
macrophages may serve as a significant replicative niche for N. gonorrhoeae and
play an important role in gonorrheal pathogenesis.
PMID- 26426086
TI - Enhancing the Therapy Experience Using Principles of Video Game Design.
AB - PURPOSE: This article considers the potential benefits that applying design
principles from contemporary video games may have on enhancing therapy
experiences. METHOD: Six principles of video game design are presented, and their
relevance for enriching clinical experiences is discussed. RESULTS: The
motivational and learning benefits of each design principle have been discussed
in the education literature as having positive impacts on student motivation and
learning and are related here to aspects of clinical practice. The essential
experience principle suggests connecting all aspects of the experience around a
central emotion or cognitive connection. The discovery principle promotes
indirect learning in focused environments. The risk-taking principle addresses
the uncertainties clients face when attempting newly learned skills in novel
situations. The generalization principle encourages multiple opportunities for
skill transfer. The reward system principle directly relates to the scaffolding
of frequent and varied feedback in treatment. Last, the identity principle can
assist clients in using their newly learned communication skills to redefine self
perceptions. CONCLUSION: These principles highlight areas for research and
interventions that may be used to reinforce or advance current practice.
PMID- 26426087
TI - Plasma Xanthine Oxidase Activity Is Predictive of Cardiovascular Disease in
Patients with Chronic Kidney Disease, Independently of Uric Acid Levels.
AB - BACKGROUND: Chronic kidney disease (CKD) is associated with increased
cardiovascular morbidity and mortality. Oxidative stress seems to play a pivotal
role in this process, and purine metabolism may be involved in CKD-related
oxidative stress. Xanthine oxidase (XO) is an enzyme involved in purine
metabolism and is also responsible for the production of reactive oxygen species.
METHODS: This prospective study aimed to analyze the relation between plasma
dosages of molecules involved in redox balance, purine metabolism and
cardiovascular events in patients with non-diabetic CKD stages 3-5 or on chronic
hemodialysis (HD). CKD (n = 51) and HD (n = 50) patients were compared to matched
healthy controls (n = 38) and followed-up for 3 years. RESULTS: Both CKD and HD
patients had decreased plasma levels of antioxidants (selenium, zinc, vitamin C).
HD patients had decreased levels of the antioxidant enzyme superoxide dismutase
and increased levels of oxidation products (ischemia-modified albumin,
malondialdehyde [MDA]). The following substrates and enzymes involved in purine
metabolism were increased in the HD cohort: adenosine, adenosine deaminase and
the pro-oxidant XO. XO activity was negatively correlated with super oxide
dismutase and positively with MDA. Interestingly, XO activity was an independent
predictor of cardiovascular events in CKD and HD patients, regardless of uric
acid levels. Uric acid was not predictive of events. CONCLUSION: This highlights
a possible role of XO itself in CKD-related cardiovascular disease (CVD) and
raises the hypothesis that beneficial effects observed with XO inhibitors on CVD
in CKD may also be due to the reduction of oxidative stress.
PMID- 26426088
TI - Why Do Patients with COPD Decline Rehabilitation.
AB - AIM: This paper aimed to suggest possible answers to the question: Why do
patients with COPD decline pulmonary rehabilitation (PR)? METHOD: The study is a
metasynthesis inspired by Noblit of the existing qualitative research on the
area. The data were collected during 2014. Six studies were found through a
systematic literature search in relevant databases. In these six studies, 65
persons were identified as decliners of PR. Four themes were identified from
these studies. RESULTS: The themes identified were as follows: the referral
process, transport problems, perception of health and other obligations or
priorities. The problems with the referral of patients relate to different areas:
the referring health professional's conviction and commitment, and the patients'
understanding of the referral. It seems that various transport problems cause
decline, for example long distance to the PR centre or the expenses of getting
back and forth. Perceptions of health cause decline. Decliners feel too sick to
join PR or do not identify themselves as a sick person, and do not want undertake
the 'patient role'. Other obligations or priorities such as work, family
obligations and vacations are prioritised on behalf of PR causing decline.
CONCLUSION: The studies included show patients' rational accounts and reflections
on declining PR. The included studies tend to describe accounts for deselection
of PR in relation to the preferences and beliefs of the patients rather than
including the social and economic variables framing the behaviour and choices of
the patients.
PMID- 26426089
TI - Amidinate-Stabilized Group 9 Metal-Silicon(I) Dimer and -Silylene Complexes.
AB - The coordination chemistry of the amidinate-stabilized silicon(I) dimer toward
group 9 metal complexes is described. The reaction of [LSi:]2 (1, L = PhC(NtBu)2)
with [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) in toluene at ambient temperature
afforded the base-stabilized silicon(I) dimer-iridium complex [LSi{Ir(cod)-MU-Cl
Ir(cod)}SiL][(cod)IrCl2] (2). In contrast, the reaction of 1 with [Rh(cod)Cl]2 in
toluene at ambient temperature afforded a mixture of the amidinate-stabilized
silicon(I) dimer-rhodium complex [LSi{Rh(cod)-MU-Cl-Rh(cod)}SiL] (3) and the
dimeric amidinate-stabilized rhodosilylene [(LSi)MU-{Rh(MU-Cl)2Rh(cod)}]2 (4).
Moreover, the latter reacted with PPh3 to afford a mixture of the Wilkinson's
catalyst [(PPh3)3RhCl] and the dimeric rhodosilylene complex [(LSi)MU
{RhCl(PPh3)}]2 (5), which underwent a rearrangement to form the rhodosilylene
phosphidorhodium dimer (LSi)[MU-{RhCl(PPh3)}MU-{RhCl(LSiPh)}](PPh2) (6).
Compounds 2-6 were characterized by NMR spectroscopy and X-ray crystallography.
In addition, DFT calculations of compound 4 were performed to understand its
electronic structure.
PMID- 26426091
TI - Computerized tomography scanning: are we optimizing catheter revision surgery in
targeted drug delivery systems?
PMID- 26426090
TI - Production of decellularized porcine lung scaffolds for use in tissue
engineering.
AB - There is a growing body of work dedicated to producing acellular lung scaffolds
for use in regenerative medicine by decellularizing donor lungs of various
species. These scaffolds typically undergo substantial matrix damage due to the
harsh conditions required to remove cellular material (e.g., high pH, strong
detergents), lengthy processing times, or pre-existing tissue contamination from
microbial colonization. In this work, a new decellularization technique is
described that maintains the global tissue architecture, key matrix components,
mechanical composition and cell-seeding potential of lung tissue while
effectively removing resident cellular material. Acellular lung scaffolds were
produced from native porcine lungs using a combination of Triton X-100 and sodium
deoxycholate (SDC) at low concentrations in 24 hours. We assessed the effect of
matrix decellularization by measuring residual DNA, biochemical composition,
mechanical characteristics, tissue architecture, and recellularization capacity.
PMID- 26426092
TI - Subgroup analysis of Japanese patients in a phase 3 study of lenvatinib in
radioiodine-refractory differentiated thyroid cancer.
AB - Lenvatinib significantly prolonged progression-free survival (PFS) versus placebo
in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) in
the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid
(SELECT) trial. This subanalysis evaluated the efficacy and safety of lenvatinib
in Japanese patients who participated in SELECT. Outcomes for Japanese patients
(lenvatinib, n = 30; placebo, n = 10) were assessed in relationship to the SELECT
population (lenvatinib, n = 261; placebo, n = 131). The primary endpoint was PFS;
secondary endpoints included overall survival, overall response rate, and safety.
Lenvatinib PFS benefit was shown in Japanese patients (median PFS: lenvatinib,
16.5 months; placebo, 3.7 months), although significance was not reached,
presumably due to sample size (hazard ratio, 0.39; 95% confidence interval, 0.10
1.57; P = 0.067). Overall response rates were 63.3% and 0% for lenvatinib and
placebo, respectively. No significant difference was found in overall survival.
The lenvatinib safety profile was similar between the Japanese and overall SELECT
population, except for higher incidences of hypertension (any grade: Japanese,
87%; overall, 68%; grade >=3: Japanese, 80%; overall, 42%), palmar-plantar
erythrodysesthesia syndrome (any grade: Japanese, 70%; overall, 32%; grade >=3:
Japanese, 3%; overall, 3%), and proteinuria (any grade: Japanese, 63%; overall,
31%; grade >=3: Japanese, 20%; overall, 10%). Japanese patients had more dose
reductions (Japanese, 90%; overall, 67.8%), but fewer discontinuations due to
adverse events (Japanese, 3.3%; overall, 14.2%). There was no difference in
lenvatinib exposure between the Japanese and overall SELECT populations after
adjusting for body weight. In Japanese patients with radioiodine-refractory
differentiated thyroid cancer, lenvatinib showed similar clinical outcomes to the
overall SELECT population. Some differences in adverse event frequencies and dose
modifications were observed. Clinical trial registration no.: NCT01321554.
PMID- 26426093
TI - Remote Loading of (64)Cu(2+) into Liposomes without the Use of Ion Transport
Enhancers.
AB - Due to low ion permeability of lipid bilayers, it has been and still is common
practice to use transporter molecules such as ionophores or lipophilic chelators
to increase transmembrane diffusion rates and loading efficiencies of
radionuclides into liposomes. Here, we report a novel and very simple method for
loading the positron emitter (64)Cu(2+) into liposomes, which is important for in
vivo positron emission tomography (PET) imaging. By this approach, copper is
added to liposomes entrapping a chelator, which causes spontaneous diffusion of
copper across the lipid bilayer where it is trapped. Using this method, we
achieve highly efficient (64)Cu(2+) loading (>95%), high radionuclide retention
(>95%), and favorable loading kinetics, excluding the use of transporter molecule
additives. Therefore, clinically relevant activities of 200-400 MBq/patient can
be loaded fast (60-75 min) and efficiently into preformed stealth liposomes
avoiding subsequent purification steps. We investigate the molecular coordination
of entrapped copper using X-ray absorption spectroscopy and demonstrate high
adaptability of the loading method to pegylated, nonpegylated, gel- or fluid
like, cholesterol rich or cholesterol depleted, cationic, anionic, and
zwitterionic lipid compositions. We demonstrate high in vivo stability of (64)Cu
liposomes in a large canine model observing a blood circulation half-life of 24 h
and show a tumor accumulation of 6% ID/g in FaDu xenograft mice using PET
imaging. With this work, it is demonstrated that copper ions are capable of
crossing a lipid membrane unassisted. This method is highly valuable for
characterizing the in vivo performance of liposome-based nanomedicine with great
potential in diagnostic imaging applications.
PMID- 26426094
TI - Ultrasound Guidance Facilitates Radial Artery Catheterization: A Meta-analysis
With Trial Sequential Analysis of Randomized Controlled Trials.
AB - BACKGROUND: Potential benefits and possible risks associated with ultrasound
guidance compared with traditional palpation for radial artery catheterization
are not fully understood. METHODS: We searched PubMed, Embase, and the Cochrane
Library through July 2015 to identify randomized controlled trials that evaluated
ultrasound guidance compared with traditional palpation for radial artery
catheterization. Primary outcome was first-attempt failure. Secondary outcomes
included mean attempts to success, mean time to success, and hematoma
complications. A random-effects model was used to estimate relative risks (RRs)
with 95% CIs. RESULTS: Twelve trials used dynamic two-dimensional (2-D)
ultrasound guidance (N = 1,992) and two used Doppler ultrasound guidance (N =
666). Compared with traditional palpation, dynamic 2-D ultrasound guidance was
associated with a reduced first-attempt failure (RR, 0.68; 95% CI, 0.52-0.87).
Trial sequential analysis showed that the cumulative z curve crossed the trial
sequential monitoring boundary for benefit establishing sufficient and conclusive
evidence. Dynamic 2-D ultrasound guidance further reduced mean attempts to
success, mean time to success, and hematoma complications. No evidence of
publication bias was detected. Compared with traditional palpation, Doppler
ultrasound guidance had no benefit on first-attempt failure (RR, 1.00; 95% CI,
0.87-1.15), which was confirmed by trial sequential analysis as the cumulative z
curve entered the futility area. CONCLUSIONS: The use of dynamic 2-D ultrasound
guidance for radial artery catheterization decreases first-attempt failure, mean
attempts to success, mean time to success, and the occurrence of hematoma
complications. Dynamic 2-D ultrasound guidance is recommended as an adjunct to
aid radial arterial catheterization.
PMID- 26426095
TI - Outcome and Prognostic Factors for Canine Splenic Lymphoma Treated by Splenectomy
(1995-2011).
AB - OBJECTIVE: To assess the outcome of canine splenic lymphoma treated with
splenectomy and to evaluate prognostic factors, including involvement of other
sites, adjuvant chemotherapy, and the effect of World Health Organization (WHO)
histological classification of canine malignant lymphoma. DESIGN: Multi
institutional, retrospective study. ANIMALS: Client-owned dogs (n = 28). METHODS:
Medical records (1995-2011) of dogs with a histological diagnosis of splenic
lymphoma and treated by splenectomy submitted by Veterinary Society of Surgical
Oncology members were reviewed. Included were dogs treated with or without
adjuvant therapy. Overall survival, disease-free interval, and cause of death
were determined. Prognostic factors and the WHO histological classification of
canine malignant lymphoma were evaluated with respect to outcome. RESULTS: Dogs
with splenic lymphoma treated by splenectomy had a 1-year survival rate of 58.8%,
after which no animals died of their disease. B cell lymphoma held a better
prognosis for survival than other variants of splenic lymphoma. Marginal zone
lymphoma and mantle cell lymphoma were the most common B cell lymphoma subtypes
in our study. Hemoabdomen and clinical signs related to splenic lymphoma,
including abdominal distention, lethargy, and anorexia, were poor prognostic
indicators, whereas disease confined to the spleen was a positive prognostic
indicator. Pre- or postoperative adjuvant chemotherapy did not provide a survival
benefit. CONCLUSION: Based on our sample population, splenectomy alone was an
effective treatment for splenic lymphoma in cases with disease confined to the
spleen. Chemotherapy may not improve survival in cases of lymphoma restricted to
the spleen.
PMID- 26426096
TI - Degradation Mechanism Induced by Psoriasis in Human Fingernails-A Different
Approach.
PMID- 26426098
TI - In cellulo protein labelling with Ru-conjugate for luminescence imaging and
bioorthogonal photocatalysis.
AB - Labelling of proteins with a luminescent ruthenium complex enables the direct
visualization and photocatalytic reduction of aryl azide in live cells. The
confinement of catalysis to the labeled proteins was visualized using an azide
based immolative linker releasing a precipitating dye.
PMID- 26426099
TI - Infection of Penile Prostheses in Patients with Diabetes Mellitus.
AB - BACKGROUND: Controversy still exists in some centers on whether diabetes mellitus
is a risk factor for penile prosthesis infection. The aim of this review is to
examine the evidence correlating penile implant infections to the presence of
diabetes mellitus in patients with organic erectile dysfunction. METHODS: We
performed a systematic review searching through Medline database from 1960 to
2014, using keywords; penile prosthesis(es), penile implant(s), and diabetes
mellitus. We used the Prisma 2009 Flow diagram for systematic reviews. Thirty
eight publications were selected for inclusion in this qualitative analysis.
RESULTS: Most case series reporting a greater infection rate in patients with
diabetes mellitus date from the 1970s to 1990s. These series reported an
infection rate of 5.5 to 20% and contained small cohort of patients. In the 1990s
larger case series reported a lower infection rate in patients with diabetes
mellitus compared with patients with paraplegia, pelvic trauma, and patients on
steroids, but still reported an infection rate as high as 10.6%. With the
implementation of antibiotic coated implants in 2001, infection rates reduced
further with reported rates becoming less than 2% in patients with diabetes
mellitus. The latest and largest case series by Eid et al. (2012) reported an
infection rate of 0.46% with antibiotic coated implants and "no touch" technique
in a cohort of 1511 cases, out of which 41% were patients with diabetes mellitus.
CONCLUSION: Strong evidence exists that the risk of penile prosthesis infection
has reduced over the decades with device improvement and surgical expertise. In
larger case series infection rates in patients with diabetes mellitus is not
statistically significant from that experiences in the population at large.
PMID- 26426100
TI - Impaired Performance of Pressure-Retarded Osmosis due to Irreversible Biofouling.
AB - Next-generation pressure-retarded osmosis (PRO) approaches aim to harness the
energy potential of streams with high salinity differences, such as wastewater
effluent and seawater desalination plant brine. In this study, we evaluated
biofouling propensity in PRO. Bench-scale experiments were carried out for 24 h
using a model wastewater effluent feed solution and simulated seawater
desalination brine pressurized to 24 bar. For biofouling tests, wastewater
effluent was inoculated with Pseudomonas aeruginosa and artificial seawater
desalination plant brine draw solution was seeded with Pseudoalteromonas
atlantica. Our results indicate that biological growth in the feed wastewater
stream channel severely fouled both the membrane support layer and feed spacer,
resulting in ~50% water flux decline. We also observed an increase in the pumping
pressure required to force water through the spacer-filled feed channel, with
pressure drop increasing from 6.4+/-0.8 bar m(-1) to 15.1+/-2.6 bar m(-1) due to
spacer blockage from the developing biofilm. Neither the water flux decline nor
the increased pressure drop in the feed channel could be reversed using a
pressure-aided osmotic backwash. In contrast, biofouling in the seawater brine
draw channel was negligible. Overall, the reduced performance due to water flux
decline and increased pumping energy requirements from spacer blockage highlight
the serious challenges of using high fouling potential feed sources in PRO, such
as secondary wastewater effluent. We conclude that PRO power generation using
wastewater effluent and seawater desalination plant brine may become possible
only with rigorous pretreatment or new spacer and membrane designs.
PMID- 26426101
TI - Isolation and characterization of Leptolyngbya sp. KIOST-1, a basophilic and
euryhaline filamentous cyanobacterium from an open paddle-wheel raceway
Arthrospira culture pond in Korea.
AB - AIMS: Cyanobacteria have been used as sustainable bioresource producers for
foods, feeds and other valuable natural products. However, selection of a new
species (other than Arthrospira), with advantageous properties for alimentary
purposes, continues to be a challenge due to potential toxicity and low biomass
productivity. In this study, we report a valuable filamentous cyanobacterium
isolated from Korea. METHODS AND RESULTS: Morphological and phylogenetic analyses
demonstrated that the isolate belongs to the genus Leptolyngbya, and consequently
designated Leptolyngbya sp. KIOST-1. Interestingly, Leptolyngbya sp. KIOST-1
possessed numerous advantageous characteristics for biomass production, similar
to Arthrospira. The isolate readily propagated in SOT medium with efficient
biomass productivity, and its optimum growth was observed at 30 degrees C under
alkaline and saline conditions. Moreover, more than half of the cellular
components in Leptolyngbya sp. KIOST-1 were composed of protein, with approx. 40%
of essential amino acids. Most importantly, no significant cytotoxicity was
detected in the isolate. CONCLUSIONS: Leptolyngbya sp. KIOST-1 has a number of
advantageous characteristics for alimentary purposes due to its efficient
productivity, high protein content and lack of potential cytotoxicity.
SIGNIFICANCE AND IMPACT OF THE STUDY: Leptolyngbya sp. KIOST-1 may be considered
a potential candidate for industrial biomass production, similar to Arthrospira.
PMID- 26426102
TI - Food consumption in patients referred for bariatric surgery with and without
binge eating disorder.
AB - INTRODUCTION: The prevalence of Binge Eating Disorder (BED) is high in obese
patients referred to bariatric surgery. Although the total energy intake is
increased, the risk of nutritional deficiencies in these patients is unknown.
This study proposes to evaluate and compare the intakes of candidate patients for
bariatric surgery with and without BED, using for this purpose the Dietary
Reference Intakes. METHODS: 116 patients referred for bariatric surgery were
submitted to nutritional, laboratory and psychological assessments. RESULTS:
Among the patients, 46.6% had BED, of these, 25.9% had the severe form. The
patients with current depression (31.9%) were more compulsive than those without
depression (p < 0.001). The mean age was significantly higher in patients without
BED (46.94 +/- 12.05 vs 42.32 +/- 10.60, p = 0.030). The only difference in
anthropometric parameters individuals with and without BED was the mid-upper arm
circumference (P = 0.047). The percentage of energy from carbohydrates was higher
in patients with BED (53.78%) than without BED (48.88%) (U = 1222, P = 0.018, r =
- 0.22). The percentage from total fat (13.63% versus 12.89%, U = 1201.0, P =
0.019, r = - 0.22) and from saturated fat (9.04% versus 8.15%, U = 1074.0, P =
0.023, r = - 0.21), was higher in patients without BED. When adjusted for the
body weight of patients, these differences were not significant. CONCLUSION:
Patients with BED eat more carbohydrates and have larger mid-upper arm
circumference in the face of similar body weight, suggesting a higher percentage
of fat mass.
PMID- 26426104
TI - Jugular pit associated with 5q14.3 deletion incorporating the MEF2C locus: a
recurrent clinical finding.
PMID- 26426103
TI - Biometric Modeling of Gene-Environment Interplay: The Intersection of Theory and
Method and Applications for Social Inequality.
AB - For more than a decade, biometric moderation models have been used to examine
whether genetic and environmental influences on individual differences might vary
within the population. These quantitative Gene * Environment interaction models
have the potential to elucidate not only when genetic and environmental
influences on a phenotype might differ, but also why, as they provide an
empirical test of several theoretical paradigms that serve as useful heuristics
to explain etiology-diathesis-stress, bioecological, differential susceptibility,
and social control. In the current article, we review how these developmental
theories align with different patterns of findings from statistical models of
gene-environment interplay. We then describe the extant empirical evidence, using
work by our own research group and others, to lay out genetically informative
plausible accounts of how phenotypes related to social inequality-physical health
and cognition-might relate to these theoretical models.
PMID- 26426113
TI - Population Prevalence of Need for Spectacles and Spectacle Ownership Among Urban
Migrant Children in Eastern China.
AB - IMPORTANCE: The number of urban migrants in China is 300 million and is
increasing rapidly in response to government policies. Urban migrants have poor
access to health care, but little is known about rates of correction of
refractive error among migrant children. This is of particular significance in
light of recent evidence demonstrating the educational impact of providing
children with spectacles. OBJECTIVE: To measure prevalence of spectacle need and
ownership among Chinese migrant children. DESIGN, SETTING, AND PARTICIPANTS:
Population-based, cross-sectional study among children who failed vision testing
(uncorrected visual acuity <=6/12 in either eye) between September 15 and 30,
2013, at 94 randomly selected primary schools in predominantly migrant
communities in Shanghai, Suzhou, and Wuxi, China. MAIN OUTCOMES AND MEASURES:
Refractive error by cycloplegic refraction; spectacle ownership, defined as
producing glasses at school, having been told to bring them; and needing glasses,
defined as uncorrected visual acuity of 6/12 or less correctable to greater than
6/12 in either eye, with myopia of -0.5 diopters (D) or less, hyperopia of +2.0 D
or greater, or astigmatism of 0.75 D or greater in both eyes. RESULTS: Among 4409
children, 4376 (99.3%) completed vision screening (mean [SD] age, 11.0 [0.81]
years; 55.3% boys; 4225 [96.5%] migrant and 151 [3.5%] local). Among 1204
children failing vision testing (total, 27.5%; 1147 migrant children [27.1%] vs
57 local children [37.7%]; P = .003), 850 (70.6%) completed refraction. Spectacle
ownership in migrant children needing glasses (147 of 640 children [23.0%]) was
less than among local children (12 of 34 children [35.3%]) (odds ratio = 0.55;
95% CI, 0.32-0.95; P = .03). Having uncorrected visual acuity less than 6/18 in
both eyes was associated positively with baseline spectacle ownership (odds ratio
= 5.73; 95% CI, 3.81-8.62; P < .001), but parental education and family wealth
were not. CONCLUSIONS AND RELEVANCE: Among urban migrant children, there was a
high prevalence of need for spectacles and a very low rate of spectacle
ownership. Spectacle distribution programs are needed specifically targeting
migrant children.
PMID- 26426114
TI - Ultratrace DNA Detection Based on the Condensing-Enrichment Effect of
Superwettable Microchips.
AB - A sensitive nucleic acid detection platform based on superhydrophilic microwells
spotted on a superhydrophobic substrate is fabricated. Due to the wettability
differences, ultratrace DNA molecules are enriched and the fluorescent signals
are amplified to allow more sensitive detection. The biosensing interface based
on superwettable materials provides a simple and cost-effective way for
ultratrace DNA sensing.
PMID- 26426115
TI - Glycerol Production from Glucose and Fructose by 3T3-L1 Cells: A Mechanism of
Adipocyte Defense from Excess Substrate.
AB - Cultured adipocytes (3T3-L1) produce large amounts of 3C fragments; largely
lactate, depending on medium glucose levels. Increased glycolysis has been
observed also in vivo in different sites of rat white adipose tissue. We
investigated whether fructose can substitute glucose as source of lactate, and,
especially whether the glycerol released to the medium was of lipolytic or
glycolytic origin. Fructose conversion to lactate and glycerol was lower than
that of glucose. The fast exhaustion of medium glucose was unrelated to
significant changes in lipid storage. Fructose inhibited to a higher degree than
glucose the expression of lipogenic enzymes. When both hexoses were present, the
effects of fructose on gene expression prevailed over those of glucose.
Adipocytes expressed fructokinase, but not aldolase b. Substantive release of
glycerol accompanied lactate when fructose was the substrate. The mass of cell
triacylglycerol (and its lack of change) could not justify the comparatively
higher amount of glycerol released. Consequently, most of this glycerol should be
derived from the glycolytic pathway, since its lipolytic origin could not be
(quantitatively) sustained. Proportionally (with respect to lactate plus
glycerol), more glycerol was produced from fructose than from glucose, which
suggests that part of fructose was catabolized by the alternate (hepatic)
fructose pathway. Earlier described adipose glycerophophatase activity may help
explain the glycolytic origin of most of the glycerol. However, no gene is known
for this enzyme in mammals, which suggests that this function may be carried out
by one of the known phosphatases in the tissue. Break up of glycerol-3P to yield
glycerol, may be a limiting factor for the synthesis of triacylglycerols through
control of glycerol-3P availability. A phosphatase pathway such as that described
may have a potential regulatory function, and explain the production of glycerol
by adipocytes in the absence of lipolytic stimulation.
PMID- 26426116
TI - Transcytosis-Targeting Peptide: A Conductor of Liposomal Nanoparticles through
the Endothelial Cell Barrier.
AB - The ultimate goal in the area of drug-delivery systems is the development of a
nanoparticle that can penetrate the endothelial cell monolayer for the targeting
of tissue parenchyma. In the present study, we identify a transcytosis-targeting
peptide (TTP) that permits polyethyleneglycol (PEG)-modified liposomes (PEG-LPs)
to penetrate through monolayers of brain-derived endothelial cells. These
endothelial cells were layered on a gelatin nanofiber sheet, a nanofiber meshwork
that allows the evaluation of transcellular transport of nanosized particles (ca.
100 nm). Systematic modification of the sequences results in the identification
of the consensus sequence of TTP as L(R/K)QZZZL, where Z denotes hydrophilic
amino acids (R/K/S and partially D). The TTP-modified liposomes are bound on the
heparin sulfate proteoglycan, and are then taken up via lipid raft-mediated
endocytosis. Subsequent intracellular imaging of the particles reveals a unique
intracellular sorting of TTP-modified PEG liposomes (TTP-PEG-LPs); namely the TTP
LPs are not localized with the lysosomes, whereas this co-localization is
dominant in the unmodified PEG liposomes (PEG-LPs). The in vivo endothelial
penetration of liposomes in adipose tissue is conferred by the dual modification
of the particles with TTP and tissue-targeting ligands. This technology promises
innovations in intravenously available delivery system to tissue parenchyma.
PMID- 26426117
TI - Development of a High-Content Orthopoxvirus Infectivity and Neutralization
Assays.
AB - Currently, a number of assays measure Orthopoxvirus neutralization with serum
from individuals, vaccinated against smallpox. In addition to the traditional
plaque reduction neutralization test (PRNT), newer higher throughput assays are
based on neutralization of recombinant vaccinia virus, expressing reporter genes
such as beta-galactosidase or green fluorescent protein. These methods could not
be used to evaluate neutralization of variola virus, since genetic manipulations
of this virus are prohibited by international agreements. Currently, PRNT is the
assay of choice to measure neutralization of variola virus. However, PRNT assays
are time consuming, labor intensive, and require considerable volume of serum
sample for testing. Here, we describe the development of a high-throughput, cell
based imaging assay that can be used to measure neutralization, and characterize
replication kinetics of various Orthopoxviruses, including variola, vaccinia,
monkeypox, and cowpox.
PMID- 26426118
TI - Host Coenzyme Q Redox State Is an Early Biomarker of Thermal Stress in the Coral
Acropora millepora.
AB - Bleaching episodes caused by increasing seawater temperatures may induce mass
coral mortality and are regarded as one of the biggest threats to coral reef
ecosystems worldwide. The current consensus is that this phenomenon results from
enhanced production of harmful reactive oxygen species (ROS) that disrupt the
symbiosis between corals and their endosymbiotic dinoflagellates, Symbiodinium.
Here, the responses of two important antioxidant defence components, the host
coenzyme Q (CoQ) and symbiont plastoquinone (PQ) pools, are investigated for the
first time in colonies of the scleractinian coral, Acropora millepora, during
experimentally-induced bleaching under ecologically relevant conditions. Liquid
chromatography-mass spectrometry (LC-MS) was used to quantify the states of these
two pools, together with physiological parameters assessing the general state of
the symbiosis (including photosystem II photochemical efficiency, chlorophyll
concentration and Symbiodinium cell densities). The results show that the
responses of the two antioxidant systems occur on different timescales: (i) the
redox state of the Symbiodinium PQ pool remained stable until twelve days into
the experiment, after which there was an abrupt oxidative shift; (ii) by
contrast, an oxidative shift of approximately 10% had occurred in the host CoQ
pool after 6 days of thermal stress, prior to significant changes in any other
physiological parameter measured. Host CoQ pool oxidation is thus an early
biomarker of thermal stress in corals, and this antioxidant pool is likely to
play a key role in quenching thermally-induced ROS in the coral-algal symbiosis.
This study adds to a growing body of work that indicates host cellular responses
may precede the bleaching process and symbiont dysfunction.
PMID- 26426119
TI - Striking Similarities in the Presentation and Duration of Illness of Influenza A
and B in the Community: A Study Based on Sentinel Surveillance Networks in France
and Turkey, 2010-2012.
AB - Influenza B represents a high proportion of influenza cases in some seasons (even
over 50%). The Influenza B study in General Practice (IBGP) is a multicenter
study providing information about the clinical, demographic and socio-economic
characteristics of patients affected by lab-confirmed influenza A or B. Influenza
B patients and age-matched influenza A patients were recruited within the
sentinel surveillance networks of France and Turkey in 2010-11 and 2011-12
seasons. Data were collected for each patient at the swab test day, after 9+/-2
days and, if not recovered, after 28+/-5 days. It was related to patient's
characteristics, symptoms at presentation, vaccination status, prescriptions of
antibiotics and antivirals, duration of illness, follow-up consultations in
general practice or emergency room. We performed descriptive analyses and
developed a multiple regression model to investigate the effect of patients and
disease characteristics on the duration of illness. Overall, 774 influenza cases
were included in the study: 419 influenza B cases (209 in France and 210 in
Turkey) and 355 influenza A cases (205 in France and 150 in Turkey). There were
no differences between influenza A and B patients in terms of clinical
presentation and number of consultations with a practitioner; however, the use of
antivirals was higher among influenza B patients in both countries. The average
(median) reported duration of illness in the age groups 0-14 years, 15-64 years
and 65+ years was 7.4 (6), 8.7 (8) and 10.5 (9) days in France, and 6.3 (6), 8.2
(7) and 9.2 (6) days in Turkey; it increased with age but did not differ by virus
type; increased duration of illness was associated with antibiotics prescription.
In conclusion, our findings show that influenza B infection appears not to be
milder disease than influenza A infection.
PMID- 26426121
TI - Interferon-gamma: The Jekyll and Hyde of Malaria.
PMID- 26426120
TI - Classification of Rhinoentomophthoromycosis into Atypical, Early, Intermediate,
and Late Disease: A Proposal.
AB - BACKGROUND: Rhinoentomophthoromycosis, or rhino-facial conidiobolomycosis, is a
rare, grossly disfiguring disease due to an infection with entomophthoralean
fungi. We report a case of rhinoentomophthoromycosis from Gabon and suggest a
staging system, which provides information on the prognosis and duration of
antifungal therapy. METHODS: We present a case of rhinoentomophthoromycosis
including the histopathology, mycology, and course of disease. For the suggested
staging system, all cases on confirmed rhinoentomophthoromycosis published in the
literature without language restriction were eligible. Exclusion criteria were
missing data on (i) duration of disease before correct diagnosis, (ii) outcome,
and (iii) confirmation of entomophthoralean fungus infection by histopathology
and/or mycology. We classified cases into atypical (orbital cellulitis, severe
pain, fever, dissemination), early, intermediate, and late disease based on the
duration of symptoms before diagnosis. The outcome was evaluated for each stage
of disease. FINDINGS: The literature search of the Medpilot database was
conducted on January 13, 2014, (updated on January 18, 2015). The search yielded
8,333 results including 198 cases from 117 papers; of these, 145 met our
inclusion criteria and were included in the final analysis. Median duration of
treatment was 4, 3, 4, and 5 months in atypical, early, intermediate, and late
disease, respectively. Cure rates were clearly associated with stage of disease
and were 57%, 100%, 82%, and 43% in atypical, early, intermediate, and late
disease, respectively. CONCLUSION: We suggest a clinical staging system that
underlines the benefit of early case detection and may guide the duration of
antifungal treatment. The scientific value of this classification is its capacity
to structure and harmonize the clinical and research approach towards
rhinoentomophthoromycosis.
PMID- 26426125
TI - Non-thermal ion desorption from an acetonitrile (CH3CN) astrophysical ice
analogue studied by electron stimulated ion desorption.
AB - The incidence of high-energy radiation onto icy surfaces constitutes an important
route for leading new neutral or ionized molecular species back to the gas phase
in interstellar and circumstellar environments, especially where thermal
desorption is negligible. In order to simulate such processes, an acetonitrile
ice (CH3CN) frozen at 120 K is bombarded by high energy electrons, and the
desorbing positive ions are analyzed by time-of-flight mass spectrometry (TOF
MS). Several fragment and cluster ions were identified, including the Hn=1-3(+),
CHn=0-3(+)/NHn=0-1(+); C2Hn=0-3(+)/CHn=0-3N(+), C2Hn=0-6N(+) ion series and the
ion clusters (CH3CN)n=1-2(+) and (CH3CN)n=1-2H(+). The energy dependence on the
positive ion desorption yield indicates that ion desorption is initiated by
Coulomb explosion following Auger electronic decay. The results presented here
suggest that non-thermal desorption processes, such as desorption induced by
electronic transitions (DIET) may be responsible for delivering neutral and ionic
fragments from simple nitrile-bearing ices to the gas-phase, contributing to the
production of more complex molecules. The derived desorption yields per electron
impact may contribute to chemical evolution models in different cold
astrophysical objects, especially where the abundance of CH3CN is expected to be
high.
PMID- 26426123
TI - Acetylation of NDPK-D Regulates Its Subcellular Localization and Cell Survival.
AB - Nucleoside diphosphate kinases (NDPK) are ubiquitous enzymes that catalyze the
reversible phosphotransfer of gamma-phosphates between di- and
triphosphonucleosides. NDPK-D (Nm23-H4) is the only member of the NDPK family
with a mitochondrial targeting sequence. Despite the high expression of NDPK-D in
the developing central nervous system, its function remains to be determined. In
this study, we show that NDPK-D knockdown induces apoptosis in neuroblastoma
cells as well as in mouse cortex, suggesting that NDPK-D is required for neuronal
survival. We identified NDPK-D as a binding partner of NAD+-dependent histone
deacetylase, SIRT1, by yeast two-hybrid screening. NDPK-D co-localized with
SIRT1, and the association of these molecules was confirmed by co
immunoprecipitation. Inhibition of SIRT1 increases the acetylation of NDPK-D.
Overexpression of NDPK-D along with SIRT1, or mutation in the acetylated lysine
residues in NDPK-D, increases its nuclear accumulation. Furthermore, the NDPK-D
acetylation-mimic mutant increased apoptosis in N1E-115 cells. Our data
demonstrate that acetylation regulates the shuttling of NDPK-D between nucleus
and cytoplasm, and increased acetylation of NDPK-D causes apoptosis.
PMID- 26426122
TI - Differential Translocation of Host Cellular Materials into the Chlamydia
trachomatis Inclusion Lumen during Chemical Fixation.
AB - Chlamydia trachomatis manipulates host cellular pathways to ensure its
proliferation and survival. Translocation of host materials into the pathogenic
vacuole (termed 'inclusion') may facilitate nutrient acquisition and various
organelles have been observed within the inclusion, including lipid droplets,
peroxisomes, multivesicular body components, and membranes of the endoplasmic
reticulum (ER). However, few of these processes have been documented in living
cells. Here, we survey the localization of a broad panel of subcellular elements
and find ER, mitochondria, and inclusion membranes within the inclusion lumen of
fixed cells. However, we see little evidence of intraluminal localization of
these organelles in live inclusions. Using time-lapse video microscopy we
document ER marker translocation into the inclusion lumen during chemical
fixation. These intra-inclusion ER elements resist a variety of post-fixation
manipulations and are detectable via immunofluorescence microscopy. We speculate
that the localization of a subset of organelles may be exaggerated during
fixation. Finally, we find similar structures within the pathogenic vacuole of
Coxiella burnetti infected cells, suggesting that fixation-induced translocation
of cellular materials may occur into the vacuole of a range of intracellular
pathogens.
PMID- 26426124
TI - Cost-Effectiveness of Including a Nurse Specialist in the Treatment of Urinary
Incontinence in Primary Care in the Netherlands.
AB - OBJECTIVE: Incontinence is an important health problem. Effectively treating
incontinence could lead to important health gains in patients and caregivers.
Management of incontinence is currently suboptimal, especially in elderly
patients. To optimise the provision of incontinence care a global optimum
continence service specification (OCSS) was developed. The current study
evaluates the costs and effects of implementing this OCSS for community-dwelling
patients older than 65 years with four or more chronic diseases in the
Netherlands. METHOD: A decision analytic model was developed comparing the
current care pathway for urinary incontinence in the Netherlands with the pathway
as described in the OCSS. The new care strategy was operationalised as the
appointment of a continence nurse specialist (NS) located with the general
practitioner (GP). This was assumed to increase case detection and to include
initial assessment and treatment by the NS. The analysis used a societal
perspective, including medical costs, containment products (out-of-pocket and
paid by insurer), home care, informal care, and implementation costs. RESULTS:
With the new care strategy a QALY gain of 0.005 per patient is achieved while
saving ?402 per patient over a 3 year period from a societal perspective. In
interpreting these findings it is important to realise that many patients are
undetected, even in the new care situation (36%), or receive care for containment
only. In both of these groups no health gains were achieved. CONCLUSION:
Implementing the OCSS in the Netherlands by locating a NS in the GP practice is
likely to reduce incontinence, improve quality of life, and reduce costs.
Furthermore, the study also highlighted that various areas of the continence care
process lack data, which would be valuable to collect through the introduction of
the NS in a study setting.
PMID- 26426126
TI - Melatonin attenuates (-)-epigallocatehin-3-gallate-triggered hepatotoxicity
without compromising its downregulation of hepatic gluconeogenic and lipogenic
genes in mice.
AB - (-)-Epigallocatehin-3-gallate (EGCG), a major constituent of green tea, can
ameliorate metabolic syndrome at least in part through reducing gluconeogenesis
and lipogenesis. Green tea extracts, of which EGCG is a key constituent, have
been used for weight loss in humans. A potential adverse effect of high-dose EGCG
or green tea extracts is hepatotoxicity. Melatonin, an endogenous antioxidant
with a high safety profile, is effective in preventing various types of tissue
damage. The current study investigated the influence of melatonin on EGCG
triggered hepatotoxicity and EGCG-downregulated hepatic genes responsible for
gluconeogenesis and lipogenesis in mice. We found that (i) melatonin extended
survival time of mice intoxicated with lethal doses of EGCG; (ii) melatonin
ameliorated acute liver damage and associated hepatic Nrf2 suppression caused by
a nonlethal toxic dose of EGCG; (iii) melatonin reduced subacute liver injury and
hepatic Nrf2 activation caused by lower toxic doses of EGCG; and (iv) melatonin
did not compromise the action of pharmacological doses of EGCG in downregulating
a battery of hepatic genes responsible for gluconeogenesis and lipogenesis,
including G6Pc, PEPCK, FOXO1alpha, SCD1, Fasn, leptin, ACCalpha, ACCbeta, GAPT,
and Srebp-1. Taken together, these results suggest that the combination of EGCG
and melatonin is an effective approach for preventing potential adverse effects
of EGCG as a dietary supplement for metabolic syndrome alleviation and body
weight reduction.
PMID- 26426127
TI - Patients' experience of partial tooth loss and expectations to treatment: a
qualitative study in Danish and Swedish patients.
AB - Knowledge of impairments, wishes and expectations is essential to make correct
decisions regarding oral rehabilitation. The purpose of this study was to
investigate discomforts, wishes and expectations in patients' with partial
edentulism before entering oral rehabilitation. In Copenhagen, Denmark, and
Malmo, Sweden, respectively, 20 patients with partial edentulism seeking
rehabilitation were interviewed in a semistructured qualitative manner. The
interviews were transcribed and analysed yielding overall domains. Six themes
appeared as overall domains: (i) experienced impairments, (ii) experienced social
awareness, (iii) expectation to treatment, (iv) expectation to
durability/survival, (v) coping strategies dealing with the tooth loss including
explanations of the tooth loss and (vi) modifications to experienced impairment.
The impairments were mostly experienced as problems in social settings. Most
participants expressed a simple wish to function normally; a fixed solution was
preferred. Many Danish participants accepted a removable solution whereas only
few Swedish participants did so. The domains 'coping strategies' and
'modifications' were not part of the chosen topics of interest, indicating a high
wish of the participants to explain their tooth loss and how they coped with it.
In conclusion, a large degree of social impairment was found in the patient group
along with several coping strategies. The impairments were modified by a number
of factors indicating that highly individualised care and treatment is needed. A
state of normality was described as the primary treatment wish with a higher
acceptance of removable solutions in Denmark than in Sweden. For final decision
making, surrounding factors seemed to influence the patients' choices.
PMID- 26426128
TI - Supramolecular Assays for Mapping Enzyme Activity by Displacement-Triggered
Change in Hyperpolarized (129)Xe Magnetization Transfer NMR Spectroscopy.
AB - Reversibly bound Xe is a sensitive NMR and MRI reporter with its resonance
frequency being influenced by the chemical environment of the host. Molecular
imaging of enzyme activity presents a promising approach for disease
identification, but current Xe biosensing concepts are limited since substrate
conversion typically has little impact on the chemical shift of Xe inside
tailored cavities. Herein, we exploit the ability of the product of the enzymatic
reaction to bind itself to the macrocyclic hosts CB6 and CB7 and thereby displace
Xe. We demonstrate the suitability of this method to map areas of enzyme activity
through changes in magnetization transfer with hyperpolarized Xe under different
saturation scenarios.
PMID- 26426129
TI - Nursing Workforce Trends Demand Transformational Leadership.
PMID- 26426130
TI - Hospital Nursing Workforce Costs, Wages, Occupational Mix,and Resource
Utilization.
AB - BACKGROUND: The objective of the study was to better understand how hospitals use
different types of RNs, LPNs, and nurse aides in proprietary (for-profit),
nonprofit, and government-owned hospitals and to estimate the wages, cost, and
intensity of nursing care using a national data set. METHOD: This is a cross
sectional observational study of 3,129 acute care hospitals in all 50 states and
District of Columbia using data from the 2008 Occupational Mix Survey
administered by the Centers for Medicare &Medicaid Services (CMS). Nursing skill
mix, hours, and labor costs were combined with other CMS hospital descriptive
data, including type of hospital ownership, urban or rural location, hospital
beds, and case-mix index. RESULTS: RN labor costs make up 25.5% of all hospital
expenditures annually, and all nursing labor costs represent 30.1%, which is
nearly a quarter trillion dollars ($216.7 billion) per year for inpatient nursing
care. On average, proprietary hospitals employ 1.3 RNs per bed and 1.9 nursing
personnel per bed in urban hospitals compared with 1.7 RNs per bed and 2.3
nursing personnel per bed for nonprofit and government-owned hospitals (P G .05).
States with higher ratios of RN compared with LPN licenses used fewer LPNs in the
inpatient setting. CONCLUSION: The findings from this study can be helpful in
comparing nursing care across different types of hospitals, ownership, and
geographic locations and used as a benchmark for future nursing workforce needs
and costs.
PMID- 26426131
TI - Mitigating Knowledge Loss: A Strategic Imperative for Nurse Leaders.
AB - With the aging of the nursing workforce and expected retirement of large numbers
of experienced nurses in the next decade, mitigating the impact that lost
knowledge will have on organizational performance and patient outcomes is
critical. The authors raise awareness of the problem, summarize observations
procured from hospital nurse executive regarding approaches for knowledge
transfer through workforce development, and pose proactive strategies for nurse
leaders who can provide direction to offset the issue before it becomes a crisis.
PMID- 26426132
TI - Retirement Financial Planning and the RN: An Integrative Literature Review.
AB - This integrative literature review examined the current research on RN
retirement. The review identified 3 critical gaps in knowledge: (a) minimal
knowledge regarding the economic impact on RN retirement, (b) incomplete
information regarding the demographics of RN retirement, and (c) a scarcity of
prospective longitudinal RN workforce studies. Future research must address these
gaps to better address RN workforce sustainability.
PMID- 26426133
TI - Correlates of New Graduate Nurses' Experiences of Workplace Mistreatment.
AB - OBJECTIVE: This study explores correlates of new graduate nurses' experiences of
workplace mistreatment. BACKGROUND: New graduate nurses' experiences of workplace
mistreatment, such as bullying, coworker incivility, and supervisor incivility,
negatively influence nurses' work and health. It is unclear whether these forms
of workplace mistreatment have similar precipitating factors and outcomes.
METHODS: We surveyed 342 new graduate nurses in Ontario to explore correlates of
3 forms of workplace mistreatment. RESULTS: Workplace incivility and bullying
were significantly related to authentic leadership, structural empowerment,
worklife fit, and psychological capital. Bullying was more strongly related to
job satisfaction, emotional exhaustion, and mental and physical health outcomes
than supervisor and coworker incivility. CONCLUSIONS: New graduate nurses'
experiences of 3 types of workplace mistreatment are related to organizational
and health factors, although bullying appears to have stronger negative effects.
PMID- 26426134
TI - Reflections on Nursing Workforce.
PMID- 26426135
TI - New Nurses' Perceptions of Hostility and Job Satisfaction: Magnet(r) Versus Non
Magnet.
AB - PURPOSE: This study investigated the perceptions of nursing hostility and job
satisfaction of new RNs, comparing the working settings of MagnetA and non-Magnet
hospitals. METHODS: An online survey of new graduate RNs wasconducted using
theNegative Acts QuestionnaireY Revised, the McCloskey/Mueller Satisfaction
Survey, the Casey-Fink Graduate Nurse Experience Survey, and a demographic
questionnaire. RESULTS: Findings indicated that RNs of Magnet and non-Magnet
facilities experienced similar hostility and job satisfaction results. Magnet
nurses (n = 226) perceived nursing hostility significantly different than non
Magnet nurses (n = 939); however, both groups reported a global perception of
nursing hostility as new RNs. CONCLUSION: Based on this study's findings, greater
consideration should be placed on orientation/residency programs, collaborative
partnerships between academia and service, zero tolerance for behaviors
undermining culture safety, and addressing nursing hostility.
PMID- 26426136
TI - Factors Influencing Critical Care Nurses' Perception of Their Overall Job
Satisfaction: An Empirical Study.
AB - OBJECTIVE: The aim of this study was to explore the factors influencing critical
care nurses' perception of their overall job satisfaction. BACKGROUND: Nurses'
job satisfaction is a key issue to consider in the retention of critical care
nurses. Shortages of nurses result in unsafe patient care, increased expense, and
increased stress levels among other nurses. METHOD: The Leadership Practices
Inventory was used among a sample of critical care nurses to measure perceived
leadership practices, the Organizational Commitment Questionnaire measured nurses
commitment, and the Job in General scale was used to measure nurses' overall job
satisfaction. Four different hypotheses were tested using bivariate and
multivariate statistical analytical techniques. RESULTS: Statistically
significant relationships were found among the following hypotheses: (a)
perceived leadership and job satisfaction; (b) organizational commitment and job
satisfaction; and (c) perceived leadership practices, organizational commitment,
and job satisfaction. No significant relationships were found among critical care
nurses' demographic variables and job satisfaction. Organizational commitment was
the strongest predictor of job satisfaction. Encourage the heart (B = 0.116, P =
.035) and organizational commitment (B = 0.353, P = .000) were found to be
significantly associated with job satisfaction. CONCLUSION: These findings have
implications for nurse educators, preceptors, administrators, recruiters, and
managers in promoting satisfaction.
PMID- 26426137
TI - Projections of the Long-Term Growth of the Registered Nurse Workforce: A Regional
Analysis.
PMID- 26426138
TI - Understanding the Role of the Professional Practice Environment on Quality of
Care in Magnet(r) and Non-Magnet Hospitals.
AB - OBJECTIVE: The aim of this study was to explore the relationship between Magnet
RecognitionA and nurse-reported quality of care. BACKGROUND: MagnetA hospitals
are recognized for nursing excellence and quality patient outcomes; however, few
studies have explored contributing factors for these superior outcomes. METHODS:
This was a secondary analysis of linked nurse survey data, hospital
administrative data, and a listing of American Nurses Credentialing Center Magnet
hospitals. Multivariate regressions were modeled before and after propensity
score matching to assess the relationship between Magnet status and quality of
care. A mediation model assessed the indirect effect of the professional practice
environment on quality of care. RESULTS: Nurse-reported quality of care was
significantly associated with Magnet Recognition after matching. The professional
practice environment mediates the relationship between Magnet status and quality
of care. CONCLUSION: A prominent feature of Magnet hospitals, a professional
practice environment that is supportive of nursing, plays a role in explaining
why Magnet hospitals have better nurse-reported quality of care.
PMID- 26426139
TI - Explaining the mechanical mechanisms of zeolitic metal-organic frameworks:
revealing auxeticity and anomalous elasticity.
AB - The comprehensive elastic properties of Zeolitic Imidazolate Frameworks (ZIF-1 to
ZIF-4) have been computed using density functional theory (DFT). We employed the
periodic CRYSTAL14 code to calculate the single-crystal elastic coefficients
(Cij) at the B3LYP level of theory. While the chemical compositions of ZIFs-1 to
4 are the same, each structure features a distinct network topology, crystal
symmetry and porosity configuration, which translate into differential structure
function mechanical correlations. We elucidate the anisotropic mechanical
response with respect to the directionally dependent Young's and shear moduli
properties. Our theoretical results suggest that ZIF-3 adopting a dft topology
has an extremely low shear resistance (Gmin = 0.1 GPa), which is also
underpinning the flexible mechanism responsible for its negative Poisson's ratio
(auxetic numin = -0.43). Interestingly, we identified that ZIF-1, ZIF-2, and ZIF
4 could exhibit a nearly zero Poisson's ratio for certain crystal orientations,
which is reminescent of a rare "cork-like" phenomenon where there is practically
no lateral deformation corresponding to an applied axial strain. Furthermore, we
determined the bulk moduli and linear compressibilities, alongside the averaged
elastic properties of the ZIF polycrystals.
PMID- 26426141
TI - The origin of a large apparent tortuosity factor for the Knudsen diffusion inside
monoliths of a samaria-alumina aerogel catalyst: a diffusion NMR study.
AB - Pulsed field gradient (PFG) NMR was applied to measure tortuosity factors for
carbon dioxide diffusion in the Knudsen and gas regimes inside monoliths of a
samaria-alumina aerogel catalyst, a high porosity material containing micropores
in addition to meso- and macropores. The apparent tortuosity factor obtained from
PFG NMR measurements for the Knudsen diffusion in the meso- and macropores of the
catalyst has an unexpectedly large value of approximately 6 if carbon dioxide
adsorption in the micropores and other types of surface adsorption sites of the
catalyst is ignored. At the same time, the corresponding apparent tortuosity
factor in the gas regime was found to be around 2. Application of a proposed
model which describes fast molecular exchange between the surface adsorption
sites and the main pore volume of the catalyst yields corrected tortuosity
factors which depend only on the pore system geometry. Using this model, the
corrected tortuosity factors were found to be around 2 for both diffusion
regimes, in agreement with the expectations based on a high porosity of the
studied catalyst.
PMID- 26426140
TI - Synthesis and Evaluation of Cytosolic Phospholipase A(2) Activatable Fluorophores
for Cancer Imaging.
AB - Activatable fluorophores selective to cytosolic phospholipase A2 (cPLA2) were
synthesized and evaluated for their ability to image triple negative breast
cancer cells. The activatable constructs were synthesized by esterification of a
small molecule fluorophore with a fatty acid resulting in ablated fluorescence.
Selectivity for cPLA2 was generated through the choice of fluorophore and fatty
acid. Esterification with arachidonic acid was sufficient to impart specificity
to cPLA2 when compared to esterification with palmitic acid. In vitro analysis of
probes incorporated into phosphatidylcholine liposomes demonstrated that a
nonselective phospholipase (sPLA2 group IB) was able to hydrolyze both
arachidonate and palmitate coupled fluorophores resulting in the generation of
fluorescence. Of the four fluorophores tested, DDAO (7-hydroxy-9H-(1,3-dichloro
9,9-dimethylacridin-2-one)) was observed to perform optimally in vitro and was
analyzed further in 4175-Luc+ cells, a metastatic triple negative human breast
cancer cell line expressing high levels of cPLA2. In contrast to the in vitro
analysis, DDAO arachidonate was shown to activate selectively in 4175-Luc+ cells
compared to the control DDAO palmitate as measured by fluorescence microscopy and
quantitated with fluorescence spectroscopy. The addition of two agents known to
activate cPLA2 enhanced DDAO arachidonate fluorescence without inducing any
change to DDAO palmitate. Inhibition of cPLA2 resulted in reduced fluorescence of
DDAO arachidonate but not DDAO palmitate. Together, we report the synthesis of a
cPLA2 selective activatable fluorophore capable of detecting cPLA2 in triple
negative breast cancer cells.
PMID- 26426143
TI - The Archean Nickel Famine Revisited.
AB - Iron formations (IF) preserve a history of Precambrian oceanic elemental
abundance that can be exploited to examine nutrient limitations on early
biological productivity. However, in order for IF to be employed as paleomarine
proxies, lumped-process distribution coefficients for the element of interest
must be experimentally determined or assumed. This necessitates consideration of
bulk ocean chemistry and which authigenic ferric iron minerals controlled the
sorption reactions. It also requires an assessment of metal mobilization
reactions that might have occurred in the water column during particle descent
and during post-depositional burial. Here, we summarize recent developments
pertaining to the interpretation and fidelity of the IF record in reconstructions
of oceanic trace element evolution. Using an updated compilation, we reexamine
and validate temporal trends previously reported for the nickel content in IF
(see Konhauser et al., 2009 ). Finally, we reevaluate the consequences of
methanogen Ni starvation in the context of evolving views of the Archean ocean
climate system and how the Ni famine may have ultimately facilitated the rise in
atmospheric oxygen.
PMID- 26426144
TI - Modification Strategies with Inorganic Acids for Efficient Photocatalysts by
Promoting the Adsorption of O2.
AB - Efficient photocatalysis for degrading environmental organic pollutants on
semiconductors requires photogenerated charge carrier separation to drive the
photochemical processes. To ensure charge separation, it is indispensable to make
charges captured effectively. Generally, the step for capturing the
photogenerated electrons by the surface adsorbed O2 is relatively slow as
compared to that for capturing holes by the surface adsorbed hydroxyl groups so
that it is taken as the rate-determining step. However, it is frequently
neglected. Thus, it is greatly desired to develop feasible strategies to promote
the adsorption of O2 for efficient photocatalysts. In this paper, we have mainly
discussed surface modification with inorganic acids, such as H3PO4, HF, and
H3BO3, to enhance photogenerated charge carrier separation based on oxygen
adsorption promotion for photocatalytic degradation of environmental pollutants.
Among these acids, the function and mechanism of H3PO4 are highlighted because of
its good performance and universality. Several important photocatalyst systems,
mainly including TiO2, alpha-Fe2O3, and g-C3N4, along with the nanostructured
carbons as electron acceptors in nanocomposites, are addressed to improve the
ability to adsorb O2. A key consideration in this review is the development of a
strategy for the promotion of adsorbed O2 for efficient photocatalysts, along
with the process mechanisms by revealing the relationships among the adsorbed O2,
photogenerated charge carrier separation, and photocatalytic performance.
Interestingly, it is suggested that the enrichment in surface acidity be
favorable for promotion of O2 adsorption, leading to the improved charge carrier
separation and then to the enhanced photoactivities of various semiconductor
photocatalysts. Moreover, several outlooks are put forward.
PMID- 26426142
TI - Crystal structure of the Legionella pneumophila Lem10 effector reveals a new
member of the HD protein superfamily.
AB - Legionella pneumophila, the intracellular pathogen that can cause severe
pneumonia known as Legionnaire's disease, translocates close to 300 effectors
inside the host cell using Dot/Icm type IVB secretion system. The structure and
function for the majority of these effector proteins remains unknown. Here, we
present the crystal structure of the L. pneumophila effector Lem10. The structure
reveals a multidomain organization with the largest C-terminal domain showing
strong structural similarity to the HD protein superfamily representatives.
However, Lem10 lacks the catalytic His-Asp residue pair and does not show any in
vitro phosphohydrolase enzymatic activity, typical for HD proteins. While the
biological function of Lem10 remains elusive, our analysis shows that similar
distinct features are shared by a significant number of HD domains found in
Legionella proteins, including the SidE family of effectors known to play an
important role during infection. Taken together our data point to the presence of
a specific group of non-catalytic Legionella HD domains, dubbed LHDs, which are
involved in pathogenesis.
PMID- 26426145
TI - Compartmentalization of Incompatible Catalytic Transformations for Tandem
Catalysis.
AB - In Nature, incompatible catalytic transformations are being carried out
simultaneously through compartmentalization that allows for the combination of
incompatible catalysts in tandem reactions. Herein, we take the
compartmentalization concept to the synthetic realm and present an approach that
allows two incompatible transition metal catalyzed transformations to proceed in
one pot in tandem. The key is the site isolation of both catalysts through
compartmentalization using a core-shell micellar support in an aqueous
environment. The support is based on amphiphilic triblock copolymers of poly(2
oxazoline)s with orthogonal functional groups on the side chain that can be used
to cross-link covalently the micelle and to conjugate two metal catalysts in
different domains of the micelle. The micelle core and shell provide different
microenvironments for the transformations: Co-catalyzed hydration of an alkyne
proceeds in the hydrophobic core, while the Rh-catalyzed asymmetric transfer
hydrogenation of the intermediate ketone into a chiral alcohol occurs in the
hydrophilic shell.
PMID- 26426146
TI - Fourier transform infrared microspectroscopy reveals biochemical changes
associated with glioma stem cell differentiation.
AB - According to the cancer stem cell theory malignant glioma is incurable because of
the presence of the cancer stem cells - a subpopulation of cells that are
resistant to therapy and cause the recurrence of a tumor after surgical
resection. Several protein markers of cancer stem cell were reported but none of
those is fully reliable to grade the content of stem cells in a tumor. Hereby we
propose Fourier transform infrared (FTIR) microspectroscopy as an alternative,
labelfree, non-damaging and fast method to identify glioma stem cells based on
their own spectral characteristics. The analysis of FTIR data revealed that in
NCH421k cells, a model of glioma stem cells, the relative content of lipids is
higher than in their all-trans retinoic acid-differentiated counterparts.
Moreover, it has been assessed that stem cells have more rigid cellular membranes
and more phosphorylated proteins, whereas after differentiation glycogen level
increases. The ability of FTIR to estimate the content of stem cells in a
heterogeneous sample, on the base of the identified spectral markers, and to
classify stem and non-stem cells into two separate populations was probed.
Although it was not possible to calculate the exact percentage of each
subpopulation, we could clearly see that with the increasing amount of
differentiated cells in a sample, more hits occupy the PC space previously
identified as a space of differentiated cells. The present study is therefore an
initial step towards the development of a FTIR based protocol in clinical
practice to estimate the content of stem cells in a tumor sample.
PMID- 26426147
TI - The Irish living kidney donor program - why potential donors do not proceed to
live kidney donation?
AB - BACKGROUND: Living donation is not only a method to increase access to kidney
transplantation but can also offer superior outcomes. We report the experience of
the living donor (LD) program in the Republic of Ireland and explore reasons why
potential donors do not proceed to live donation. METHODS: Retrospective cohort
study of all potential donors from January 2000 to March 2014 who presented
wishing to undergo donor work-up and their subsequent outcomes. RESULTS: A total
of 956 donors for 496 recipients contacted the live kidney donation program of
which 883 potential donors proceeded to the initial stage of assessment. The
donor dropout rate at this stage was 64.2% (614/956 potential donors did not
proceed to further evaluation). Thereafter, 269 (28.1%) donors underwent further
assessment by the multidisciplinary team. In total, 93 (9.7%) donors were
declined following this assessment with 176 (18.4%) donors ultimately proceeding
to live kidney donation. The major reason for declining a donor was a medical
contraindication (n = 63, 67.7%). In term of recipients, 54.2% (n = 269/496) had
a potential donor proceed for further assessment of which 65.4% (n = 176/269)
ultimately proceeding to live donation. CONCLUSION: Further evaluation of the
declined donor group is warranted to allow for expansion of the LD program.
PMID- 26426148
TI - The Effect of Breathing, Movement, and Meditation on Psychological and Physical
Symptoms and Inflammatory Biomarkers in Inflammatory Bowel Disease: A Randomized
Controlled Trial.
AB - BACKGROUND: This study evaluated the effects of the Breath-Body-Mind Workshop
(BBMW) (breathing, movement, and meditation) on psychological and physical
symptoms and inflammatory biomarkers in inflammatory bowel disease (IBD).
METHODS: Twenty-nine IBD patients from the Jill Roberts IBD Center were
randomized to BBMW or an educational seminar. Beck Anxiety Inventory, Beck
Depression Inventory, Brief Symptom Inventory 18, IBD Questionnaire, Perceived
Disability Scale, Perceived Stress Questionnaire, Digestive Disease Acceptance
Questionnaire, Brief Illness Perception Questionnaire, fecal calprotectin, C
reactive protein, and physiological measures were obtained at baseline and weeks
6 and 26. RESULTS: The BBMW group significantly improved between baseline and
week 6 on Brief Symptom Inventory 18 (P = 0.02), Beck Anxiety Inventory (P =
0.02), and IBD Questionnaire (P = 0.01) and between baseline and week 26 on Brief
Symptom Inventory 18 (P = 0.04), Beck Anxiety Inventory (P = 0.03), Beck
Depression Inventory (P = 0.01), IBD Questionnaire (P = 0.01), Perceived
Disability Scale (P = 0.001), and Perceived Stress Questionnaire (P = 0.01) by
paired t tests. No significant changes occurred in the educational seminar group
at week 6 or 26. By week 26, median C-reactive protein values decreased
significantly in the BBMW group (P = 0.01 by Wilcoxon signed-rank test) versus no
significant change in the educational seminar group. CONCLUSIONS: In patients
with IBD, participation in the BBMW was associated with significant improvements
in psychological and physical symptoms, quality of life, and C-reactive protein.
Mind-body interventions, such as BBMW, which emphasize Voluntarily Regulated
Breathing Practices, may have significant long-lasting benefits for IBD symptoms,
anxiety, depression, quality of life, and inflammation. BBMW, a promising
adjunctive treatment for IBD, warrants further study.
PMID- 26426153
TI - A tiered, integrated biological and chemical monitoring framework for
contaminants of emerging concern in aquatic ecosystems.
AB - The chemical-specific risk-based paradigm that informs monitoring and assessment
of environmental contaminants does not apply well to the many thousands of new
chemicals that are being introduced into ambient receiving waters. We propose a
tiered framework that incorporates bioanalytical screening tools and diagnostic
nontargeted chemical analysis to more effectively monitor for contaminants of
emerging concern (CECs). The framework is based on a comprehensive battery of in
vitro bioassays to first screen for a broad spectrum of CECs and nontargeted
analytical methods to identify bioactive contaminants missed by the currently
favored targeted analyses. Water quality managers in California have embraced
this strategy with plans to further develop and test this framework in regional
and statewide pilot studies on waterbodies that receive discharge from municipal
wastewater treatment plants and stormwater runoff. In addition to directly
informing decisions, the data obtained using this framework can be used to
construct and validate models that better predict CEC occurrence and toxicity.
The adaptive interplay among screening results, diagnostic assessment and
predictive modeling will allow managers to make decisions based on the most
current and relevant information, instead of extrapolating from parameters with
questionable linkage to CEC impacts. Integr Environ Assess Manag 2016;12:540-547.
(c) 2015 SETAC.
PMID- 26426152
TI - High-throughput genotyping of Anopheles mosquitoes using intact legs by Agena
Biosciences iPLEX.
AB - Recent developments in genotyping technologies coupled with the growing desire to
characterize genome variation in Anopheles populations open the opportunity to
develop more effective genotyping strategies for high-throughput screening. A
major bottleneck of this goal is nucleic acid extraction. Here, we examined the
feasibility of using intact portions of a mosquito's leg as sources of template
DNA for whole-genome amplification (WGA) by primer-extension preamplification. We
used the Agena Biosciences MassARRAY((r)) platform (formerly Sequenom) to
genotype 78 SNPs for 265 WGA leg samples. We performed nucleic acid extraction on
36 mosquito carcasses and compared the genotype call concordance with their
corresponding legs and observed full concordance. Using three legs instead of one
improved genotyping success rates (96% vs. 89%, respectively), although this
difference was not significant. We provide a proof of concept that WGA reactions
can be performed directly on mosquito legs, thereby eliminating the need to
extract nucleic acid. This approach is straightforward and sensitive and allows
both species determination and genotyping of Anopheles mosquitoes to be performed
in a high-throughput manner. Our protocol also leaves the mosquito body intact
facilitating other experimental analysis to be undertaken on the same sample.
Based on our findings, this method would also be suitable for use with other
insect species.
PMID- 26426154
TI - Drosophila glob1 expresses dynamically and is required for development and
oxidative stress response.
AB - Biological significance of the globin protein family could be ascertained by
their conservation through archaea to human. Globin(s) have been "classically"
studied as oxygen binding protein(s), with recent implications in a host of other
physiological functions. Drosophila melanogaster possesses three globin genes
(glob1, glob2, glob3) located at different cytogenetic positions. We have
performed a comprehensive investigation on the cellular expression profile and
functional relevance of glob1 in Drosophila development. A profound level of
maternally contributed glob1 gene products was found during early embryogenesis.
Subsequently, commencement of zygotic transcription leads to its strong
expression in somatic muscles, gut primordia, fat bodies, tracheal cells, etc.
Similarly, dynamic expression of glob1 was evident in most of the larval tissues,
interestingly with high expression in dividing cells. Reduced expression of glob1
leads to various impairments and lethality during embryogenesis and larval
development. A substantial increase in level of cellular ROS was also evident due
to reduced expression of glob1 which consequently leads to locomotor impairment
and early aging in surviving adult flies. To best of our knowledge, this is the
first report which demonstrates that in addition to oxygen management, globin
gene(s) are also involved in regulating various aspects of development in
Drosophila.
PMID- 26426158
TI - Radiotracer investigations in pilot-scale soakers.
AB - This paper describes a radiotracer investigation carried out to measure residence
time distribution (RTD) of petroleum residues in pilot-scale soakers. The main
objectives of the investigation were to evaluate the feasibility of using bromine
82 as dibromobiphenyl (DBBP) for tracing the petroleum residues (organic phase)
as a radiotracer at elevated temperature and pressure, and to investigate the
flow dynamics of the phase in the soaker at different operating and process
conditions. The measured RTD was treated and mean residence times (MRTs) were
determined. Tanks-in-series with backmixing model (TISBM) was used to simulate
the measured RTD data. The results of model simulation indicated a high degree of
backmixing in the soaker without baffles i.e. without sectionalizing the soaker.
However, the introduction of perforated plates at various axial locations inside
the soaker i.e. sectionalizing the soaker, reduces the extent of backmixing thus
tending the flow towards plug flow.
PMID- 26426155
TI - Expression of stem cell-related genes in the endometrium and endometriotic
lesions: a pilot study.
AB - OBJECTIVE: To compare the expression of stem cell-related genes in the
endometrium (END), superficial endometriosis (SE), and deep infiltrating
endometriosis (DIE). STUDY DESIGN: We performed a prospective pilot study of six
women suffering from SE and DIE who gave consent for laparoscopy surgery,
endometrial biopsies, and participation in this study. Quantitative RT-PCR
analysis of 84 stem cell-related genes was performed in 18 biopsy samples.
RESULTS: A total of 40 of 84 genes were expressed in SE and DIE, but were
different from END as follows. Seven genes were over-expressed in SE and 33 genes
were under-expressed in DIE compared with END. Two genes were only over-expressed
in SE and three genes were only over-expressed in DIE. Six under-expressed genes
were exclusively located in SE and one was only located in DIE. The remaining 31
genes were not different among the groups. There was no significant difference in
gene expression between SE and DIE samples. CONCLUSION: Tissue of DIE and SE
appears to have similar stem cell-related genes. Nevertheless, there are
differences in gene expression between SE and DIE.
PMID- 26426159
TI - Maxillofacial trauma in the emergency department: pearls and pitfalls in airway
management.
AB - Maxillofacial trauma poses a challenge for the anesthesiologist because injuries
can often compromise the patient's airways. Airway maintenance is the first step
in the American College of Surgeons Advance Trauma Life Support (ATLS(r))
protocol. However, clinical dilemmas may arise about the best way to manage a
potentially life-threatening injury. There are no recommendations about the best
time to intubate, the warning signs for deciding to intubate, or which device
should be used when difficulty is expected. In this context the ATLS(r) approach
is important but not sufficient. It is also necessary to recognize and be able to
manage specific problems in this scenario where clinical priorities may be
conflicting, may suddenly change or may be hidden. This clinical review discusses
the complexity of this scenario, providing an overview of the conditions at
greatest risk for airway obstruction and the options for airway management, on
the basis of the recent literature. Clinicians must recognize the milestones and
pitfalls of this topic in order to adopt a systematic approach for airway
management, to identify specific characteristics associated with it, and to
establish the utility of different instruments for airway management.
PMID- 26426160
TI - Pulmonary pathophysiology in obesity: did we miss something?
PMID- 26426161
TI - Influence of therapeutic cancer radiation on the bond strength of an epoxy- or an
MTA-based sealer to root dentine.
AB - AIM: To evaluate the influence of radiation on root canal sealer push-out bond
strength to dentine and sealer/dentine interface in teeth filled with AH Plus
(Dentsply Ind. Com. Ltda, Petropolis, RJ, Brazil) and MTA Fillapex (Angelus Ind.
Prod. Odontologicos S/A, Londrina, PR, Brazil). METHODOLOGY: Thirty-two maxillary
canines were selected and randomly assigned to 2 groups (n = 16): one group was
not irradiated, and the other was subjected to a cumulative radiation dose of 60
Gy. Root canals were prepared with the Reciproc system (VDW GmbH, Munich,
Germany), and each group was divided into 2 subgroups (n = 8) according to the
sealer - AH Plus or MTA Fillapex - using the single-cone filling technique. Then,
1-mm-thick dentine slices were obtained from each root third for the push-out
test to evaluate sealer bond strength to dentine and for scanning electron
microscopy (SEM) to examine the sealer/dentine interface. Failure mode after
debonding was determined with a stereomicroscope at *25 magnification. Bond
strength data were analysed by two-way anova with a split-plot design and post
hoc Tukey's test (alpha = 0.05). RESULTS: Significantly lower bond strength (P <
0.0001) was obtained after irradiation (0.71 +/- 0.20 versus 0.97 +/- 0.29 MPa)
and in specimens filled with MTA Fillapex (0.70 +/- 0.18 MPa) compared with AH
Plus (1.00 +/- 0.27 MPa). Percentage of adhesive failures increased after
radiation in all root thirds in the teeth filled with AH Plus. SEM revealed more
gap-containing regions and fewer tags at the sealer/dentine interface in
irradiated specimens, with more tag formation and fewer gaps with AH Plus sealer.
CONCLUSIONS: Radiation was associated with a decrease in the push-out bond
strength of sealers to intraradicular dentine and formation of more gaps and
fewer tags at the sealer/dentine interface regardless of the sealer.
PMID- 26426162
TI - Identification of immunodominant antigens for the laboratory diagnosis of
toxocariasis.
AB - OBJECTIVES: To identify immunodominant antigens of Toxocara canis recognised by
Toxocara-infected sera as recombinant reagents for immunodiagnosis of
toxocariasis. METHODS: Pooled sera from human cases of toxocariasis were used to
identify immunodominant antigens by immunoscreening a T. canis larval expression
cDNA library. The positive clones were sequenced to reveal the identity of the
antigens. The recombinant proteins were expressed in E. coli and then used to
confirm their immunoreaction with sera of humans with toxocariasis. Two chosen
antigens were also used to differentiate Toxocara infection from other helminth
infections in mice. RESULTS: Eleven antigens with immunodiagnostic potential were
identified, including two C-type lectins (CTLs) that reacted strongly with the
Toxocara-positive serum pool. The first CTL (Tc-CTL-1) is the same as TES-32,
previously identified as a major immunodominant component of TES; the second CTL
(Tc-CTL-2) is a novel C-type lectin sharing 83% amino acid sequence identity
within the functional domain of Tc-CTL-1. The E. coli-expressed recombinant Tc
CTL-1 was strongly recognised by the Toxocara-positive serum pool or sera from
animals experimentally infected with T. canis. Reactivity with recombinant Tc-CTL
1 was higher when the unreduced protein was used in an enzyme-linked
immunosorbent assay (ELISA), dot-blot assay or Western blot test compared to the
protein under reduced condition. Both recombinant Tc-CTL-1- and Tc-CTL-2-based
ELISAs were able to differentiate T. canis infection from other helminth
infections in experimentally infected mice. CONCLUSIONS: Both Tc-CTL-1 and Tc-CTL
2 were able to differentiate Toxocara infection from other helminth infections
and could potentially be used as sensitive and specific immunodiagnostic
antigens.
PMID- 26426163
TI - Effects of particle size and hydro-thermal treatment of feed on performance and
stomach health in fattening pigs.
AB - Effects of grinding and hydro-thermal treatment of feed on growth performance,
slaughter traits, nutrient digestibility, stomach content and stomach health were
examined by using 96 crossbred fattening pigs. Pigs were fed a grain-soybean meal
based diet processed by various technical treatments. Feeding groups differed in
particle size after grinding (finely vs. coarsely ground feed) and hydro-thermal
treatment (without hydro-thermal treatment, pelleting, expanding, expanding and
pelleting). Fine grinding and hydro-thermal treatment showed significant
improvements on the digestibility of crude nutrients and content of metabolisable
energy. Hydro-thermal treatment influenced average daily gain (ADG) and average
daily feed intake (DFI) significantly. Finely ground pelleted feed without
expanding enhanced performances by increasing ADG and decreasing feed-to-gain
ratio (FGR) of fattening pigs. Coarsely ground feed without hydro-thermal
treatment resulted in the highest ADG and DFI, however also in the highest FGR.
Expanded feed decreased DFI and ADG. Slaughter traits were not affected by
treatments. Coarsely ground feed without hydro-thermal treatment had protective
effects on the health of gastric pars nonglandularis, however, pelleting
increased gastric lesions. Hydro-thermal treatment, especially expanding,
resulted in clumping of stomach content which possibly induced satiety by slower
ingesta passage rate and thus decreased feed intake. Pigs fed pelleted feed
showed less pronounced development of clumps in stomach content compared with
expanded feed.
PMID- 26426165
TI - Priapism in Homozygous Sickle Cell Disease: A 40-year Study of the Natural
History.
AB - OBJECTIVES: To describe the incidence, pattern, and outcome of priapism in
homozygous sickle cell (SS) disease. METHODS: Regular review, for periods up to
40 years, was done of all 162 males with SS disease detected during the screening
of 100 000 consecutive non-operative deliveries at the main government maternity
hospital in Kingston, Jamaica, between June 1973 and December 1981. RESULTS:
Priapism occurred in 52 (32.7%) patients overall, the incidence rising steeply in
late adolescence to 32% by age 20 years and a cumulative incidence of nearly 60%
of patients by age 40 years. Many cases were elicited only on direct questioning
because of embarrassment and the lack of realization that priapism complicates SS
disease. Initial events were recurrent stuttering episodes in 39 patients, a
single short-term event in six patients and a major attack (more than six hours)
in seven patients. Erectile function was preserved in almost all patients with
simple stuttering or single events. Major attacks (> 6 hours) occurred in 17
patients, preceded by stuttering episodes in nine, by a single event in one, and
occurring de novo in seven. In these, erectile function was unknown in five,
deemed satisfactory in five (sometimes improving over three years), weak in three
and impotence persisted in four (two with major attacks three and six months
previously). CONCLUSION: A history of stuttering priapism should be routinely
enquired and prophylactic measures used if attacks exceed once weekly. Major
events generally result in short-term impotence, but the late recovery of
erectile function cautions against the early insertion of penile prostheses.
PMID- 26426164
TI - Biosimilar Epoetin Zeta in Oncology and Haematology: Development and Experience
following 6 Years of Use.
AB - Chemotherapy-induced anaemia is frequent in cancer patients, with severity
depending on the extent of the disease and intensity of treatment. Clinical
guidelines recommend erythropoietin therapy to treat or prevent anaemia in some
oncology/haematology patients being treated with chemotherapy. The patent expiry
of the first-generation erythropoietins has led to the development of biosimilar
products, i.e. therapeutic proteins exhibiting comparable quality, safety and
efficacy to an existing reference biological medicine, the patent of which has
expired. This review summarises the available data set supporting the use of one
such biosimilar product, epoetin zeta (RetacritTM) in oncology/haematology. The
body of evidence supporting the use of epoetin zeta continues to grow, with post
marketing clinical studies underway to evaluate its longer-term clinical efficacy
and safety. Biosimilar medicines have the potential to offer cost savings to
health care providers, with the assurance of ongoing risk management programmes
to ensure patient safety.
PMID- 26426166
TI - Healthy Eating in Jamaica: The Cost Factor.
AB - OBJECTIVE: This study was conducted to determine the importance of food cost in
securing a healthy diet to combat non-communicable diseases. Several studies have
evaluated whether healthier foods or diets cost more but a full range of health
criteria has rarely been explored. Rather than merely comparing high and low
energy dense foods, this study also included type of fat, vitamin, mineral and
fibre content of foods in classifying them as healthy and less healthy. METHOD:
Both 'commonly consumed' and 'all available' foods were ranked according to their
nutritional value and potential positive or negative contribution to the
development of major health problems in Jamaica such as obesity and chronic
diseases. The costs of 158 food items were averaged from supermarkets, municipal
markets and wholesale outlets in six parishes across Jamaica. Cost differentials
were then assessed in comparing healthy and less healthy foods. RESULTS: The
study found that among the commonly consumed foods in Jamaica, healthy options
cost J$88 (US$0.78) more than less healthy ones. However, when all the available
food items were considered, the less healthy options cost more. The cheapest
daily cost of a nutritionally balanced diet in Jamaica varied considerably by
parish but was on average J$269 (US$2.40) per person. For a family of three, this
translates approximately to the total minimum wage per week. CONCLUSION: Eating
healthy in Jamaica can be achieved at low cost if appropriate information on
nutrient content/value for money is provided to consumers. Effective promotions
by public and private sector agencies are essential for consumer choice to be
optimal.
PMID- 26426167
TI - The Protective Effect of Epigallocatechin-3-gallate on Paraquat-induced
Haemolysis.
AB - Epigallocatechin-3-gallate (EGCG) is a major ingredient present in green tea,
which has a high antioxidant activity. In this study, the effect of EGCG was
investigated on paraquat-induced haemolysis of erythrocyte membrane. Erythrocytes
were incubated in 0.03, 0.3, 3.0 and 30 mg/mL EGCG, respectively and exposed to
30 mg/mL of paraquat for 10 minutes. The effect of paraquat was determined by an
analysis of the osmotic fragility of the erythrocytes. The results showed that
EGCG (30 mg/mL) significantly (p < 0.05) reduced the haemolysis of erythrocytes
exposed to paraquat (5.0 mg/mL). This suggests that EGCG may have a protective
effect on paraquat-induced erythrocyte membrane haemolysis and that consumption
of green tea, with high EGCG concentration, could ameliorate the deleterious
effect of paraquat toxicity on the haemolysis of erythrocyte membrane.
PMID- 26426168
TI - Effect of L-ornithine L-aspartate on Liver Injury Due to Acute Ethyl Alcohol
Intoxication in Rats.
AB - OBJECTIVE: Ethyl alcohol is a substance that is widely used worldwide and known
to exert toxic effects on liver. In this study, we aimed to examine the effect of
L-ornithine L-aspartate (LOLA) on the toxicity of a single dose of ethyl alcohol
in rats. SUBJECTS AND METHOD: We used 32 randomly selected male Sprague-Dawley
rats weighing 200-250 g. The rats were grouped into four groups with each group
containing eight rats: Group 1: the control group, Group 2: the ethyl alcohol
group, Group 3: the LOLA group and Group 4: the ethyl alcohol+LOLA group. Ethyl
alcohol was administered orally through a nasogastric tube at a dose of 6 g/kg
after diluting with distilled water. One hour after ethyl alcohol administration,
LOLA was administered to pre-specified groups orally through a nasogastric tube
at a dose of 200 mg/kg after diluting with distilled water. Liver tissue and
blood samples were obtained from all rats 24 hours later to study total
antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index
(OSI) levels in liver samples, and aspartate aminotransferase (AST), alanine
transferase (ALT), TAC, TOS and OSI levels in blood samples. RESULTS: Serum TAC,
TOS and OSI levels were higher in the groups that were administered ethyl
alcohol. In addition, tissue TAC level was higher and TOS and OSI levels were
lower in groups that were given ethyl alcohol. No significant changes were
observed in serum and tissue TAC, TOS, OSI, ALT and AST levels in the LOLA
administered groups. CONCLUSION: This study showed that LOLA was not
biochemically effective and exerts no oxidative stress reducing activity in liver
injury due to acute ethyl alcohol toxicity.
PMID- 26426169
TI - Alcoholic Extract of Lotus Leaves Improves Lipid Profile in Rats with HIV
Protease Inhibitor-induced Dyslipidaemia.
AB - OBJECTIVE: To examine the effect of the alcoholic extract of lotus leaves (AELL)
on antiretroviral treatment-induced dyslipidaemia in a rat model. METHODS: Lotus
leaves were extracted by 95% ethanol. Seventy male Sprague-Dawley rats were given
lopinavir/ritonavir for six weeks. At week 0 and 6, sera were collected for
measurement of total cholesterol (TC) and triglyceride (TG). Rats meeting the
criteria for dyslipidaemia were assigned to four groups and received once daily
for another four weeks lopinavir/ritonavir (group A), lopinavir/ritonavir plus
0.52 g/kg AELL (group B), lopinavir/ritonavir plus 0.26 g/kg AELL (group C), or
lopinavir/ritonavir plus 0.13 g/kg AELL (group D), respectively. At weeks 8 and
10, blood samples were collected again for measurement of TC or TG. RESULTS: Both
TC and TG increased over time in group A during the observation period (weeks 6
to 10), however, TC and TG decreased in group B, and TG declined in group C.
Neither TC nor TG could be reduced to a level near baseline. CONCLUSION:
Alcoholic extract of lotus leaves may have the potential to treat dyslipidaemia
related to highly active antiretroviral therapy, but may not be potent enough to
reduce TC or TG concentrations to goal levels when used alone.
PMID- 26426170
TI - Prevalence of Chronic Kidney Disease among Patients Attending a Specialist
Diabetes Clinic in Jamaica.
AB - OBJECTIVE: To estimate the prevalence of chronic kidney disease (CKD) among
patients attending the University Hospital of the West Indies (UHWI) Diabetes
Clinic and to determine the proportion of patients at high risk for adverse
outcomes. METHODS: We conducted a cross-sectional study among patients attending
the UHWI Diabetes Clinic between 2009 and 2010. Trained nurses administered a
questionnaire, reviewed dockets, and performed urinalyses. Estimated glomerular
filtration rate (eGFR) was calculated using the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equation. Albuminuria was assessed using
urine test strips for protein and microalbumin. Chronic kidney disease was
defined as an eGFR < 60 ml/min/1.73m2 or albuminuria >= 30 mg/g creatinine. Risk
of adverse outcome (all-cause mortality, cardiovascular disease and kidney
failure) was determined using the Kidney Disease: Improving Global Outcome
(KDIGO) 2012 prognosis grid. RESULTS: Participants included 100 women and 32 men
(mean age, 55.4 +/- 12.9 years, mean duration of diabetes, 16.7 +/- 11.7 years).
Twenty-two per cent of participants had eGFR < 60 ml/min/1.73m2. Moderate
albuminuria (30-300 mg/g) was present in 20.5% of participants and severe
albuminuria (> 300 mg/g) in 62.1%. Overall prevalence of CKD was 86.3% (95%CI
80.4%, 92.2%). Based on KDIGO risk categories, 50.8% were at high risk and 17.4%
at very high risk of adverse outcomes. CONCLUSION: Most patients at the UHWI
Diabetes Clinic had CKD and were at high or very high risk of adverse outcomes.
Further studies to determine the burden of CKD in other clinical settings and to
identify the best strategies for preventing adverse outcomes in developing
countries need to be conducted.
PMID- 26426171
TI - Application of Modified Glomerular Filtration Rate Estimation Equations in
Chinese Diabetic Patients with Chronic Kidney Diseases.
AB - OBJECTIVE: To evaluate the applicability of modified formulae based on plasma
creatinine levels in Chinese diabetic patients with chronic kidney diseases
(CKD). METHODS: A total of 294 diabetic patients were investigated. Glomerular
filtration rate (GFR) was estimated with the Ruijin equation, Cockcroft-Gault
(CG) and Modification of Diet in Renal Disease (MDRD) formulae. The accuracy of
estimated GFR was compared with technetium-99m diethylene triamine pentaacetic
acid (99mTc-DTPA)-GFR (sGFR). RESULTS: Bland-Altman analysis demonstrated that
the Ruijin equation was more consistent with sGFR than the other equations.
However, all the equations were not very consistent with sGFR. The analysis
showed that the slope of the Ruijin equation was closer to the identical line and
indicated that the bias of Ruijin equation was lowest. The 15%, 30% and 50%
accuracies of the Ruijin equation were higher than those of the other equations;
the 30% accuracy of Ruijin equation was more than 70%. CONCLUSION: Ruijin
equation is more applicable in Chinese diabetic and CKD patients.
PMID- 26426172
TI - Evaluation of Nutritional Biochemical Parameters in Haemodialysis Patients over a
Ten-year Period.
AB - AIM: Protein-energy malnutrition as well as systemic inflammation and metabolic
disorders are common in patients with chronic kidney failure, who require renal
replacement therapy (haemodialysis). Such malnutrition is a factor that
significantly contributes to their morbidity and mortality. This study evaluated
the nutritional status of haemodialysis patients by assessing biochemical and
anthropometric parameters in order to determine whether these patients suffered
disorders reflecting nutritional deterioration directly related to time on
haemodialysis. SUBJECTS AND METHOD: This research comprised 90 patients of both
genders with chronic kidney failure, who regularly received haemodialysis at our
unit over a period of ten years. The patients' blood was tested quarterly for
plasma albumin, total cholesterol and total proteins, and tested monthly for
transferrin. The patients' weight, height and body mass index (BMI) were
monitored. Body mass index was calculated using the formula: weight (kg)/height
(m2 ) and classified in one of the following categories defined in the World
Health Organization (WHO) Global Database on Body Mass Index: (i) underweight
[BMI < 18.50], (ii) normal [BMI 18.50 - 24.99], (iii) overweight [BMI 25 -
29.99], (iv) obese [BMI > 30]. RESULTS: In the ten-year period of the study, the
patients experienced a substantial decline in their biochemical parameters.
Nevertheless, their BMI did not show any significant changes despite the
patients' state of malnutrition. CONCLUSIONS: The prevalence of malnutrition in
haemodialysis patients was evident. Nevertheless, the BMI of the subjects did not
correspond to the biochemical parameters measured. Consequently, the results
showed that the nutritional deterioration of these patients was mainly reflected
in their biochemical parameters rather than in their anthropometric measurements.
PMID- 26426173
TI - Treatment Experience of Severe Abdominal Infection after Orthotopic Liver
Transplantation.
AB - This study aims to investigate the causes and treatment experience of severe
abdominal infection after orthotopic liver transplantation. Clinical data were
retrospectively analysed in perioperative severe abdominal infection of 186
orthotopic liver transplantation cases from March 2004 to November 2011. Among
the 186 patients, 16 cases had severe abdominal infection: five cases had bile
duct anastomotic leakage-inducing massive hydrops and infection under liver
interstice, 10 cases had extensive bleeding of surgical wound leading to massive
haematocele and infection around the liver, and one case had postoperative lower
oesophageal fistula leakage causing massive hydrops and infection under the left
diaphragm. After definite diagnosis, 12 cases underwent surgery within three
days, with no death. Among the four cases that underwent surgery three days after
diagnosis, one case died of multiple-organ failure five days after abdominal
cavity exploration, which was performed 21 days after liver transplantation.
Severe abdominal infections after liver transplantation were the most common
causes of death in perioperative liver transplantation. Comprehensive treatment
with efficacious antibiotics, multiple-organ support, controlled surgical removal
of the lesion, and adequate drainage establishment was the key to the entire
treatment.
PMID- 26426174
TI - Time-dependent Degradation Pattern of Cardiac Troponin T in Cases of Death by
Burn.
AB - OBJECTIVE: Death due to burn occurs frequently. This study investigated time
dependent alterations in cardiac troponin T (cTnT) associated with fatal burns.
METHODS: Cardiac tissue samples were collected from 10 medico-legal autopsies
after informed consent from the relatives and post-mortem degradation by
incubation of the cardiac tissue was studied at room temperature for different
time periods. The cases included in this study were the subjects of burns without
any prior history of disease who died in the hospital and their exact time of
death was known. An efficient extraction protocol to analyse the banding pattern
of cTnT in post-mortem tissue was developed. RESULTS: The data show a distinct
time-dependent profile corresponding to the degradation of cTnT by proteases
found in cardiac muscle. Both post-mortem interval and cardiac tissue of burned
corpses had a statistically significant effect where the greatest amount of
protein breakdown was observed within the first 41.20 hours, after which intact
protein slowly disappears. The average molecular weight of all fragments showed
intact cTnT to be rapidly degraded into smaller fragments. CONCLUSION: In cases
of burns, such knowledge will assist in knowing if there were previous scars that
might have mimicked a burn and also help to properly evaluate the real cause of
death.
PMID- 26426175
TI - Treatment of Parapelvic Cyst by Internal Drainage Technology Using Ureteroscope
and Holmium Laser.
AB - BACKGROUND: The aim of parapelvic cyst treatment is to have complete drainage of
cyst fluid and prevent its further compression of the kidney and collective
system. This study explores the efficacy and safety of surgical approaches with
holmium laser ureteroscopic internal drainage in the treatment of parapelvic
cyst. METHODS: The compression effect of parapelvic cyst on the renal collective
system was observed by rigid ureteroscope using retrograde ureteroscopic
technology. With direct vision, the cyst wall on the obvious parapelvic
compression site was cut. The diameter of the cyst wall cut was about 1 cm. The
internal drainage was obtained by double-J tubes. When the cyst was in the
inferior pole of kidney or where the rigid ureteroscope could not reach, a
flexible ureteroscope was used. RESULTS: In 28 cases of operation, 27 cases were
successful. The cyst treatment time was eight to 40 minutes (average 26 minutes).
During the operation, no massive haemorrhage, damage of nearby organ and ureter,
or other complications happened. Time of follow-up was 10-72 months (average 39
months). The results of follow-up showed that in 22 cases, the cyst disappeared;
the diameter of the cyst in four cases was reduced by more than half, and one
case recurred. CONCLUSION: The treatment of parapelvic cyst by internal drainage
operation using holmium laser and ureteroscopy was effective. The operation was
safe with few complications.
PMID- 26426176
TI - Ascites in Ovarian Carcinoma - Reliability and Limitations of Cytological
Analysis.
AB - OBJECTIVE: The objective of this study was to examine the validity of ascitic
fluid cytology in the detection of pathological findings, to examine the
percentage of false positive and false negative results in the cytology of
ascitic fluid and to determine the validity of peritoneal cytology in relation to
the histopathological type of the ovarian tumour. METHODS: This retrospective
study included 170 peritoneal cytology findings. The study was conducted from
January 2010 to December 2012. The experimental group included 76 cytology
findings obtained from patients diagnosed with ovarian carcinoma, whereas the
control group was composed of 94 cytology findings of benign ovarian tumours and
liver cirrhosis ascites. The patients with ovarian carcinoma had grades III, as
well as grades I and IIc but only in cases where operative and pathological
finding indicated a ruptured or perforated tumour capsule. RESULTS: The
sensitivity of peritoneal cytology is 68.92%, specificity is 93.61%, positive
predictive value is 89.65% and negative predictive value is 78.57%. In 30.02% of
patients, the peritoneal cytology showed false negative results, while in 6.38%,
the results were false positive. The highest percentage of false negative
findings was 77%, found in endometrioid carcinoma. CONCLUSION: Peritoneal
cytology of ascitic fluid is highly specific but has relatively low sensitivity,
particularly in the case of endometrioid ovarian carcinoma. In order to increase
sensitivity, peritoneal cytology should be combined with monoclonal antibodies
and other biochemical and immunohistochemical markers.
PMID- 26426177
TI - Analysing Biological Rhythms in Fibromyalgia Syndrome.
AB - AIM: This study evaluated biological rhythm disorders in patients with
fibromyalgia syndrome (FMS). METHODS: The study enrolled 82 patients with FMS and
82 controls. Pain intensity was evaluated using a visual analogue scale (VAS).
The psychological conditions of the patients were evaluated using the Beck
Depression Inventory (BDI). The Biological Rhythms Interview of Assessment in
Neuropsychiatry (BRIAN) was used to assess disturbances in biological rhythms (ie
sleep, activity, social and eating patterns). RESULTS: There was no difference
between the two groups at baseline (all p > 0.05). The BDI, BRIAN total, sleep,
activity, social, and eating scores were higher in patients with FMS than in the
controls (all p < 0.001). Further, a significant correlation was found between
biological rhythms and BDI scores (p < 0.001) and there were positive
correlations between the VAS score and BRIAN total, sleep, and eating and BDI in
patients with FMS (all p < 0.001). CONCLUSION: There are marked biological rhythm
disturbances in FMS. There is an important relationship between rhythm disorders
and FMS. The disturbances in sleep, functional activities, social participation,
and disordered rhythms like eating patterns show the need for a multidisciplinary
approach to treating patients with FMS.
PMID- 26426178
TI - Estimated Burden of Serious Fungal Infections in Jamaica by Literature Review and
Modelling.
AB - OBJECTIVE: Jamaica is one of the largest countries in the Caribbean with a
population of 2 706 500. Prevalence of human immunodificency virus (HIV) in
Jamaica is high, while that of tuberculosis (TB) is recorded to be low. In this
study, we have estimated the burden of serious fungal infections and some other
mycoses in Jamaica. METHODS: All published papers reporting on rates of fungal
infections in Jamaica and the Caribbean were identified through extensive search
of the literature. We also extracted data from published papers on epidemiology
and from the World Health Organization (WHO) TB Programme and UNAIDS. Chronic
pulmonary aspergillosis (CPA), allergic bronchopulmonary aspergillosis (ABPA) and
severe asthma with fungal sensitization (SAFS) rates were derived from asthma and
TB rates. Where there were no available data on some mycoses, we used specific
populations at risk and frequencies of fungal infection of each to estimate
national prevalence. RESULTS: Over 57 600 people in Jamaica probably suffer from
serious fungal infections each year, most related to 'fungal asthma' (ABPA and
SAFS), recurrent vulvovaginal candidiasis and AIDS-related opportunistic
infections. Histoplasmosis is endemic in Jamaica, though only a few clinical
cases are known. Pneumocystis pneumonia is frequent while cryptococcosis and
aspergillosis are rarely recorded. Tinea capitis is common in children. Recurrent
vulvovaginal candidiasis is very common (3154/100 000) and candidaemia occurs.
Subcutaneous mycoses such as chromoblastomycosis and mycetoma also seem to be
relatively common. CONCLUSION: Local epidemiological studies are urgently
required to validate or modify these estimates of serious fungal infections in
Jamaica.
PMID- 26426180
TI - Simvastatin Protects Osteoblasts from the Deleterious Effects of the Liquid
Milieu of Multiple Myeloma.
AB - Lytic bone lesions are the main clinical manifestation of multiple myeloma. The
intense variety in this cell microenvironment, composed mainly of fibroblasts,
osteoblasts, osteoclasts, immune cells and mesenchymal cells, is influenced by
the massive presence of neoplastic plasma cells. Studies with statins have
reported their action in stimulating the formation and reducing bone resorption.
The aim of this study was to verify the in vitro response of human osteoblasts
exposed to the supernatant (liquid milieu) of multiple myeloma. The data obtained
indicate that simvastatin has positive effects on the growth of osteoblasts and
protection against the anti-proliferative effects of multiple myeloma
supernatant.
PMID- 26426179
TI - Mini-review: Obesity in Caribbean Youth.
AB - OBJECTIVE: Our focus was on the determination of the growing number of youths of
every race and ethnicity, diagnosed with obesity and its co-morbidities in the
Caribbean. We reviewed the causes and strategies to combat obesity, and the
implications of the fast food industry in enabling the escalation of obesity.
METHODS: We consulted several databases such as PubMed, MEDLINE, the Obesity Gene
Map Database, and the USEPA Toxicity Reference Database. Organizations such as
the World Health Organization (WHO), Centers for Disease Control and Prevention
(CDC), Organization for Economic Co-operation and Development (OECD) and the Pan
American Health Organization (PAHO) were used as information sources. RESULTS:
Transgenerational effects and triggers like obesogens, pathogens, environmental
stress, antibiotics and gut microbiota are some of the causes of obesity, and
some of these triggers are imprinted epigenetically early in embryonic
development, leading to lifelong obesity. With an estimated population of 42
million in the Caribbean, the economic cost of obesity, including medical,
absenteeism, presenteeism, insurance, disability, direct and indirect cost, was
estimated cost of 68.5 billion USD with 88.2 million quality-adjusted life years
lost. CONCLUSION: Genome-wide association studies have established that genetics
play a role in the aetiology of this "non-communicable" disease. While the
development of personalized interventions according to genotype is futuristic, we
must focus on effective nutrition and physical education classes in schools and
establishing monitoring programmes using simple tools such as scales and tape
measures as suggested intervention. A Pigovian tax to control the fast food
industry is mandatory. Nevertheless, lifestyle adjustment, including alterations
in diet and increased physical activity, continues to be a sound recommendation.
PMID- 26426181
TI - Oral Hygiene and Handwashing Practices among Middle School Students in 15 Latin
American and Caribbean Countries.
AB - OBJECTIVE: To examine the relationship between infrequent toothbrushing and
infrequent handwashing among middle school students from 15 Latin American and
Caribbean countries (Antigua and Barbuda, Argentina, British Virgin Islands,
Cayman Islands, Costa Rica, Grenada, Guatemala, Guyana, Peru, Saint Kitts and
Nevis, Saint Lucia, Saint Vincent and Grenadines, Suriname, Trinidad and Tobago,
and Uruguay). METHODS: A secondary analysis was done of nationally-representative
data from 33 174 middle school students who participated in the Global School
based Student Health Survey (GSHS) between 2006 and 2011. RESULTS: In all 15
countries, the association between rarely brushing or cleaning teeth and rarely
handwashing after using the toilet was significant for both boys and girls. The
pooled odds ratio for this association was 6.7 (5.8, 7.7). CONCLUSION: Healthcare
providers who notice signs of poor dental hygiene or infrequent bathing in
adolescents should consider providing comprehensive hygiene education to their
patients, since infrequent oral and body hygiene behaviours tend to co-exist and
both are threats to health.
PMID- 26426182
TI - Correlation of Radiographic Mental Foramen Position and Occulusion in Three
Different Indian Populations.
AB - BACKGROUND: The knowledge of the position of the mental foramen (MF) is important
for administering local anaesthesia for diagnostic, surgical or operative
procedures. AIMS: To determine the shape, position, symmetry of MF and its
continuity with the inferior dental canal (IDC) on a digital panoramic view and
to find its correlation with Angle's molar relations in three Indian
subpopulations. The study also determines the correlation of inter-foramen
distance in both genders of three Indian subpopulations. SUBJECTS AND METHODS:
One hundred and twenty digital panoramic radiographs were evaluated from three
Indian subpopulations (Punjab, Rajasthan and Northeast [NE]). The assessment of
occlusion was based on Angle's molar relationships. The data obtained were
statistically analysed. RESULTS: The commonest position of the MF in the
Rajasthan and NE populations was position 4 bilaterally, while in the Punjab
population, it was position 3 on the right and position 4 on the left side. The
majority of the MF was round in shape followed by oval. The mean distance between
two MF was highest among the Punjab male population and least among the NE female
population. The most frequent pattern of MF continuity with IDC was diffuse in
Rajasthan population, separated in NE and continuous in Punjab. Correlation
between Angle's molar relation with MF position was significant for Classes I and
II but not for Class III. Correlation of inter-foramen distance between genders
was highly significant in the NE and Punjab populations. CONCLUSION: The
commonest MF position was aligned with the 1st premolar and between the 1st and
2nd premolar.
PMID- 26426184
TI - Amlodipine-induced Gingival Hyperplasia - A Case Report and Review.
AB - Anticonvulsants, antihypertensive calcium channel blockers and immunosuppressants
are the three main classes of drugs known to cause drug-induced gingival
hypertrophy or hyperplasia. Among the calcium channel blockers, nifedipine
administration has most frequently been associated with medication-related
gingival hyperplasia. The incidence with amlodipine, which has a mode of action
pharmacodynamically comparable to nifedipine, has rarely been reported. Here, we
present a rare case of amlodipine-induced gingival hyperplasia in a hypertensive
patient.
PMID- 26426183
TI - Paroxysmal Complete Atrioventricular Block: A Rare Cause of Syncope in Children.
AB - Paroxysmal atrioventricular block (PAVB) is a rare cause of syncope, mostly
reported in adults. In the present study, a child with recurrent syncope due to
PAVB is reported. A 12-year old boy was admitted due to syncope. Some syncopal
episodes were consistent with vasovagal syncope, while others had atypical
features. Electrocardiography, echocardiography and 24-hour electrocardiography
monitoring were normal. Head-up tilt table test revealed mixed type vasovagal
syncope. With beta-blocker treatment, the frequency of syncopal episodes
decreased; however, the episodes with atypical features continued. Intracardiac
electrophysiological study was normal, but repeated external loop recorder
monitoring revealed transient AVB during a syncopal episode. In children with
syncope with atypical features, PAVB should be kept in mind. Repeated external
loop recorder monitoring may be useful in the diagnosis of such seldom seen
arrhythmic causes.
PMID- 26426185
TI - Functional Outcomes of the Surgery and Rehabilitation in a Challenging Case of
Heterotopic Ossification after Encephalitis.
AB - Heterotopic ossification is the formation of the lamellar bone where normally
osseous tissue does not exist. Since heterotopic ossification can cause severe
functional loss, it is a challenging condition for both clinicians and patients.
Neurogenic heterotopic ossification is a rare condition after encephalitis.
Likewise, in this paper, we have presented a challenging case of heterotopic
ossification after viral encephalitis and functional outcomes after the
management of heterotopic ossification.
PMID- 26426186
TI - Rare Seagull Cooing Murmur from Acute Aortic Dissection.
AB - Acute aortic dissection is a rare but potentially fatal disease. The early
recognition of this disease is important for timely treatment. Some signs and
symptoms, such as past history of hypertension, tearing pain and pulselessness,
can provide valuable clues to the diagnosis of this disease. In this case study,
the mechanism of a seagull murmur from aortic dissection is first described. This
information is potentially useful for the differential diagnosis of dissection.
PMID- 26426187
TI - Repeated Burkholderia cepacia Peritonitis in a Patient Undergoing Continuous
Ambulatory Peritoneal Dialysis.
AB - Burkholderia cepacia (B cepacia) is a rare opportunistic pathogen in continuous
ambulatory peritoneal dialysis (CAPD) peritonitis. We describe the first case of
repeated B cepacia CAPD peritonitis, occurring in an outpatient environment,
treated with antimicrobial medication without peritoneal catheter removal. B
cepacia may lead to repeat infection, therefore, we should insist on catheter
removal during each peritonitis episode.
PMID- 26426188
TI - A Reduction Grade of Lipodystrophy and Limited Side Effects after HAART Regimen
with Raltegravir, Lamivudine, Darunavir and Ritonavir in an HIV-1 Infected
Patient after Six Years of Antiretroviral Therapy.
AB - HIV-associated lipodystrophy commonly presents with fat loss in the face,
buttocks, arms and legs, hypocomplementaemia, glomerulonephritis, and autoimmune
disorders. The exact mechanism of HIV-associated lipodystrophy is not fully
elucidated. There is evidence indicating that it can be caused by both
antiretroviral medications and HIV infection in the absence of antiretroviral
medication. Lipodystrophy seems to be mainly due to HIV-1 protease inhibitors.
Interference with lipid metabolism is postulated as pathophysiology. Also, the
development of lipodystrophy is associated with specific nucleoside reverse
transcriptase inhibitors (NRTI). Mitochondrial toxicity is postulated to be
involved in the pathogenesis associated with NRTI. Here, we analyse the side
effects and examine the impact of the highly active antiretroviral therapy
(HAART) regimen including raltegravir, lamivudine, darunavir and ritonavir in an
HIV-1 infected patient with severe lipodystrophy after six years of
antiretroviral therapy.
PMID- 26426189
TI - Tricuspid Atresia 18 Years Post Glenn: Is Fontan Necessary in All Cases?
AB - Tricuspid atresia is a rare cyanotic congenital heart disease, first described by
Kreysig (1817), has an incidence of 1% to 5%. It is incompatible with longevity
without surgical intervention. Glenn (1958) was successful in using a superior
vena cava to right pulmonary artery anastomosis. Fontan (1958) was successful in
separating the right and left cardiac circulation; this is the surgical method of
choice, with death of 17% by 20 years of age. The Fontan circulation has burdens
of multisystem abnormalities, including ventricular dysfunction (72%),
dysrhythmias (40%) and renal, hepatic, gastrointestinal and pulmonary
complications. The index case is the oldest documented report of tricuspid
atresia with rudimentary right ventricle and concordant ventriculo-arterial
connections, 18 years post Glen only, from two years of age. She is asymptomatic,
of high intellect, never used medications and is now functioning at New York
Heart Association (NYHA) I-II, at 20 years of age. Her survival and function was
secondary to an innate large atrial and ventricular communication with normal
left ventricle, mitral, aortic and pulmonary valves, indicating Fontan may not be
needed in all structural anatomic cases of tricuspid atresia.
PMID- 26426190
TI - Valvar Pulmonary Atresia in Afro-Caribbean Adolescents: Echocardiographic
Features.
AB - Valvar pulmonary atresia is a rare congenital anomaly usually associated with
ventricular septal defects or intact ventricular septum. The patent ductus
arteriosus (56%) and systemic pulmonary collaterals maintain pulmonary blood
flow. Presentation beyond childhood is unusual, as there is usually high
morbidity in the first year of life. The two index cases highlight the rarity of
adolescents with valvar pulmonary atresia and focusses on the transthoracic
echocardiographic features, whose diagnoses provide definitive and curative
options with adequate size pulmonary dimensions. Options available are
transcatheter interventional radiofrequency pulmonary valvotomy, which is both
diagnostic and therapeutic, and intraoperative valve replacement, thus
eliminating the need for right ventricle pulmonary artery external valved conduit
during corrective surgery. They are the first cases of adolescents with isolated
cardiac anomaly of valvar pulmonary atresia, documented in Afro-Caribbeans.
PMID- 26426191
TI - The Non-recurrent Laryngeal Nerve -- A Rare Phenomenon Which Requires Vigilance.
PMID- 26426193
TI - Extradural Haematoma in Football.
PMID- 26426192
TI - Parathyroid Carcinoma: A Case Report and Review of the Literature.
PMID- 26426194
TI - The Significance of Evaluating the Variation of Mechanical Microstructure for
Hypertrophic Cardiomyopathy Using Diffusion Tensor Magnetic Resonance Imaging.
PMID- 26426195
TI - Adrenal Cystic Lymphangioma.
PMID- 26426196
TI - Closing the Gap between Preclinical Biologic Development and Clinical Application
in Rheumatoid Arthritis.
PMID- 26426197
TI - Lack of awareness of treatment failure among HIV-1-infected patients in Guinea
Bissau - a retrospective cohort study.
AB - INTRODUCTION: With more people receiving antiretroviral treatment (ART), the need
to detect treatment failure and switch to second-line ART has also increased. We
assessed CD4 cell counts (as a marker of treatment failure), determined the rate
of switching to second-line treatment and evaluated mortality related to
treatment failure among HIV-infected patients in Guinea-Bissau. METHODS: In this
retrospective cohort study, adult patients infected with HIV-1 receiving >=6
months of ART at an HIV clinic in Bissau were included from June 2005 to July
2014 and followed until January 2015. Treatment failure was defined as 1) a fall
in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100
cells/uL after >=6 months of ART. Cox hazard models, with time since six months
of ART as the time-varying coefficient, were used to estimate the hazard ratio
for death and loss to follow-up. RESULTS: We assessed 1,591 HIV-1-infected
patients for immunological treatment failure. Treatment failure could not be
determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the
remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%)
with failure were switched from first- to second-line ART. The overall switching
rate was 3.1 per 100 person-years. Mortality rate was higher in patients with
than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95%
CI: 0.9-107.8), 7.6 (95% CI: 1.6-35.5) and 3.1 (95% CI: 1.5-6.3) in the first,
second and following years, respectively. During the first year of follow-up,
patients experiencing treatment failure had a higher risk of being lost to follow
up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI:
1.7-11.8). CONCLUSIONS: We found a high rate of treatment failure, an alarmingly
high number of patients for whom treatment failure could not be assessed, and a
low rate of switching to a second-line therapy. These factors could lead to an
increased risk of resistance development and excess mortality.
PMID- 26426198
TI - Estimated and Measured GFR Associate Differently with Retinal Vasculopathy in the
General Population.
AB - BACKGROUND/AIMS: Estimated glomerular filtration rate (eGFR) is used extensively
in epidemiological research. Validations of eGFR have demonstrated acceptable
performance, but the dependence of creatinine and cystatin C on non-GFR factors
could confound associations with disease. Few studies have investigated this
issue in direct comparison with measured GFR (mGFR). We compared the associations
between eGFR and mGFR and retinal vasculopathy, a marker of systemic
microvasculopathy. METHODS: Iohexol clearance and retinal photography were
examined in the Renal Iohexol Clearance Survey in Tromso 6, which consists of a
representative sample of middle-aged persons from the general population. A total
of 1,553 persons without self-reported kidney disease, cardiovascular disease or
diabetes were investigated. Three eGFR equations based on creatinine and/or
cystatin C from the Chronic Kidney Disease Epidemiology Collaboration were
studied. Differences between eGFR and mGFR were analyzed with seemingly unrelated
regression methods. RESULTS: mGFR in the lowest quartile was associated with an
increased multivariable-adjusted odds ratio of retinopathy (OR 1.86, 95% CI 1.16
2.97), but not with retinal artery or vein diameters. eGFR based on cystatin C
(eGFRcys) was consistently biased relative to mGFR in its associations with
retinal vessel diameters across different models. eGFR based on creatinine
(eGFRcrea) and eGFR based on both creatinine and cystatin C were also biased in
several of these models (p < 0.05). For retinopathy, the differences between the
3 eGFR and mGFR measurements were not statistically significant. CONCLUSIONS: Low
mGFR is associated with retinopathy in the general population. eGFR based on
creatinine and/or cystatin C are not valid substitutes for mGFR in studies of the
relationship between the retina and kidney function in healthy persons.
PMID- 26426199
TI - Human Inducible Pluripotent Stem Cells and Autism Spectrum Disorder: Emerging
Technologies.
AB - Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental
condition. Symptoms of ASD cover the spectrum from mild qualitative differences
in social interaction to severe communication and social and behavioral
challenges that require lifelong support. Attempts at understanding the
pathophysiology of ASD have been hampered by a multifactorial etiology that
stretches the limits of current behavioral and cell based models. Recent progress
has implicated numerous autism-risk genes but efforts to gain a better
understanding of the underlying biological mechanisms have seen slow progress.
This is in part due to lack of appropriate models for complete molecular and
pharmacological studies. The advent of induced pluripotent stem cells (iPSC) has
reinvigorated efforts to establish more complete model systems that more reliably
identify molecular pathways and predict effective drug targets and candidates in
ASD. iPSCs are particularly appealing because they can be derived from human
patients and controls for research purposes and provide a technology for the
development of a personalized treatment regimen for ASD patients. The
pluripotency of iPSCs allow them to be reprogrammed into a number of CNS cell
types and phenotypically screened across many patients. This quality is already
being exploited in protocols to generate 2-dimensional (2-D) and three
dimensional (3-D) models of neurons and developing brain structures. iPSC models
make powerful platforms that can be interrogated using electrophysiology, gene
expression studies, and other cell-based quantitative assays. iPSC technology has
limitations but when combined with other model systems has great potential for
helping define the underlying pathophysiology of ASD. Autism Res 2016, 9: 513
535. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 26426200
TI - Bright-Yellow-Emissive N-Doped Carbon Dots: Preparation, Cellular Imaging, and
Bifunctional Sensing.
AB - Fluorescent carbon dots (CDs) have attracted much attention in recent years
because of their superior optical and chemical properties, thus demonstrating
many potential applications. However, the previously reported CDs mostly show
strong emission only in the blue-light region, and the long-wavelength (i.e.,
yellow- to red-light) emissions are usually very weak. Such a drawback restricts
their further applications, particularly in the biology-relevant fields. Herein,
a rare example of N-doped CDs that emit bright-yellow fluorescence (i.e., y-CDs)
is reported using 1,2,4-triaminobenzene as carbon precursor. The as-prepared y
CDs exhibit not only respectable emission quantum yield and highly optical
stabilities but superior biocompatibility and biolabeling potentials. In
addition, the y-CDs are found to show an interesting "ON-OFF-ON" three-state
emission with the stepwise addition of Ag(+) and cysteine (Cys), indicating
potential applications as a bifunctional sensing platform. Thanks to the highly
intense emission of y-CDs, the gradual quenching and restoration of their
fluorescence with the addition of Ag(+) and further Cys could also be observed
with the naked eye. More importantly, the ensemble of the y-CDs and Ag(+)
demonstrates practicability for the highly selective and sensitive detection of
Cys in human plasma samples with satisfactory results.
PMID- 26426201
TI - Heterodimers formed through a partial anionic exchange process: scanning
tunneling spectroscopy to monitor bands across the junction vis-a-vis
photoinduced charge separation.
AB - We report controlled formation of heterodimers and their charge separation
properties. CdS|CdTe heterodimers were formed through an anionic exchange process
of CdS nanostructures. With control over the duration of the anionic exchange
process, bulk|dot, bulk|bulk, and then dot|bulk phases of the semiconductors
could be observed to have formed. A mapping of density of states as derived from
scanning tunneling spectroscopy (STS) brought out conduction and valence band
edges along the nanostructures and heterodimers. The CdS|CdTe heterodimers
evidenced a type-II band-alignment between the semiconductors along with the
formation of a depletion region at the interface. The width (of the depletion
region) and the energy-offset at the interface depended on the size of the
semiconductors. We report that the width that is instrumental for photoinduced
charge separation in the heterodimers has a direct correlation with the
performance of hybrid bulk-heterojunction solar cells based on the nanostructures
in a polymer matrix.
PMID- 26426202
TI - Rust fungal effectors mimic host transit peptides to translocate into
chloroplasts.
AB - Parasite effector proteins target various host cell compartments to alter host
processes and promote infection. How effectors cross membrane-rich interfaces to
reach these compartments is a major question in effector biology. Growing
evidence suggests that effectors use molecular mimicry to subvert host cell
machinery for protein sorting. We recently identified chloroplast-targeted
protein 1 (CTP1), a candidate effector from the poplar leaf rust fungus
Melampsora larici-populina that carries a predicted transit peptide and
accumulates in chloroplasts and mitochondria. Here, we show that the CTP1 transit
peptide is necessary and sufficient for accumulation in the stroma of
chloroplasts. CTP1 is part of a Melampsora-specific family of polymorphic
secreted proteins. Two members of that family, CTP2 and CTP3, also translocate in
chloroplasts in an N-terminal signal-dependent manner. CTP1, CTP2 and CTP3 are
cleaved when they accumulate in chloroplasts, while they remain intact when they
do not translocate into chloroplasts. Our findings reveal that fungi have evolved
effector proteins that mimic plant-specific sorting signals to traffic within
plant cells.
PMID- 26426203
TI - Role of (H2O)(n) (n = 2-3) Clusters on the HO2 + O3 Reaction: A Theoretical
Study.
AB - We report a theoretical investigation on the role of the water dimer and trimer
in the reaction between the hydroperoxyl radical and ozone. This study is part of
an ongoing series of research endeavors that intend to deliver a comprehensive
understanding on the role of water on this reaction. Due to the complexity of the
potential energy surface, and to be able to make comparisons with our previous
works, our calculations have employed model chemistries based on the Kohn-Sham
DFT formalism. It is found that the calculated reaction paths share a common
scheme, not only in the context of this work, but also in consideration of our
previous studies. Also, oxygen-abstraction barriers are always submerged, with
the relative energy between the hydrogen- and oxygen-abstraction saddle-points
increasing with the number of water molecules, which maintain an apparent
spectator role. Finally, we report novel HO2...(H2O)3 and HO3...(H2O)n complexes
originating from our reaction schemes.
PMID- 26426204
TI - The Effect of Luting Cement and Titanium Base on the Final Color of Zirconium
Oxide Core Material.
AB - PURPOSE: To evaluate the effects of different types of luting cements and
different colors of zirconium cores on the final color of the restoration that
simulates implant-supported fixed partial dentures (FPDs) by using a titanium
base on the bottom. MATERIALS AND METHODS: One hundred and twenty zirconium oxide
core plates (Zr-Zahn; 10 mm in width, 5 mm in length, 0.5 mm in height) were
prepared in different shades (n = 20; noncolored, A2, A3, B1, C2, D2). The
specimens were subdivided into two subgroups for the two types of luting cements
(n = 10). The initial color measurements were made on zirconium oxide core plates
using a spectrometer. To create the cement thicknesses, stretch strips with holes
in the middle (5 mm in diameter, 70 MUm in height) were used. The second
measurement was done on the zirconium oxide core plates after the application of
the resin cement (U-200, A2 Shade) or polycarboxylate cement (Lumicon). The final
measurement was done after placing the titanium discs (5 mm in diameter, 3 mm in
height) in the bottom. The data were analyzed with two-way ANOVA and Tukey's
honestly significant differences (HSD) tests (alpha = 0.05). RESULTS: The ?E*ab
value was higher in the resin cement-applied group than in the polycarboxylate
cement-applied group (p < 0.001). The highest ?E*ab value was recorded for the
zirconium oxide core-resin cement-titanium base, and the lowest was recorded for
the polycarboxylate cement-zirconium oxide core (p < 0.001). CONCLUSION: The
luting cement, the presence of titanium, and the color of zirconium are all
important factors that determine the final shade of zirconia cores in implant
supported FPDs.
PMID- 26426205
TI - DNA methylation status as a biomarker of anti-epidermal growth factor receptor
treatment for metastatic colorectal cancer.
AB - Anti-epidermal growth factor receptor (EGFR) treatment is an effective option for
metastatic colorectal cancer (CRC) treatment. However, there are few reliable
biomarkers to predict the clinical response to anti-EGFR treatment. We
investigated the genome-wide DNA methylation status in metastatic colorectal
cancer to identify associations between the methylation status and clinical
response to anti-EGFR antibody. We retrospectively reviewed the medical records
of 97 patients (45 patients for the first cohort and 52 patients for the second
cohort) who received anti-EGFR treatment for KRAS wild-type metastatic CRC. Then
we analyzed the associations between genome-wide DNA methylation status and
clinical response to anti-EGFR treatment, and evaluated the predictive power and
value of the methylation status statistically. As a result, each cohort was
classified into highly methylated CRC and low methylated CRC subgroups by
unsupervised clustering analyses. In the first cohort, clinical outcomes were
significantly better in the low methylated CRC subgroup than in the highly
methylated CRC subgroup (response rate, 35.7% vs 6.3%, P = 0.03; disease control
rate, 75% vs 31.3%, P = 0.005; hazard ratio for progression-free survival, 0.27;
95% confidence interval, 0.13-0.57, P < 0.001; overall survival, 0.19; 95%
confidence interval, 0.06-0.54, P < 0.001). These results were reproducible in
the second cohort. The genome-wide methylation status was a predictive factor of
progression-free survival and overall survival independently of RAS mutation
status. In conclusion, we found that the genome-wide DNA methylation status is a
powerful epigenetic predictor of anti-EGFR treatment in patients with KRAS wild
type metastatic colorectal cancer (UMIN000005490).
PMID- 26426207
TI - Exploring Expressive Vocabulary Variability in Two-Year-Olds: The Role of Working
Memory.
AB - PURPOSE: This study explored whether measures of working memory ability
contribute to the wide variation in 2-year-olds' expressive vocabulary skills.
METHOD: Seventy-nine children (aged 24-30 months) were assessed by using
standardized tests of vocabulary and visual cognition, a processing speed
measure, and behavioral measures of verbal working memory and phonological short
term memory. RESULTS: Strong correlations were observed between phonological
short-term memory, verbal working memory, and expressive vocabulary. Speed of
spoken word recognition showed a moderate significant correlation with expressive
vocabulary. In a multivariate regression model for expressive vocabulary, the
most powerful predictor was a measure of phonological short-term memory
(accounting for 66% unique variance), followed by verbal working memory (6%), sex
(2%), and age (1%). Processing speed did not add significant unique variance.
CONCLUSIONS: These findings confirm previous research positing a strong role for
phonological short-term memory in early expressive vocabulary acquisition. They
also extend previous research in two ways. First, a unique association between
verbal working memory and expressive vocabulary in 2-year-olds was observed.
Second, processing speed was not a unique predictor of variance in expressive
vocabulary when included alongside measures of working memory.
PMID- 26426206
TI - Design and preparation of matrine surface-imprinted material and studies on its
molecule recognition selectivity.
AB - A matrine molecule surface-imprinted material was designed and prepared using an
effective surface-imprinting technique developed by our group, and its molecular
recognition performance and mechanism were investigated in depth. Monomer
glycidyl methacrylate (GMA) was first graft-polymerized on the surfaces of micron
sized silica gel particles in surface-initiated graft polymerization manner,
obtaining the grafted particles PGMA/SiO(2) with high grafting degree.
Subsequently, the ring-opening reaction of the epoxy groups of the grafted
macromolecules PGMA with 5-aminosalicylic acid (5-ASA) was carried out, resulting
in the functional grafted particle SA-PGMA/SiO(2), on whose surfaces salicylic
acid as functional group was chemically bonded. By right of the mutual strong
secondary bond forces, electrostatic interaction and hydrogen bonding, SA
PGMA/SiO(2) particles produced strong adsorption for matrine. Finally, with this
strong adsorption, matrine molecule surface imprinting was carried out on the
surfaces of SA-PGMA/SiO(2) particles with ethylene glycol diglycidyl ether as
cross-linking agent, resulting in the matrine molecule surface-imprinted material
MIP-SAP/SiO(2). The binding characteristic of MIP-SAP/SiO(2) toward matrine was
investigated in depth with both batch and column methods and using oxymatrine and
cytisine as two contrast alkaloids. The experimental results show that MIP
SAP/SiO(2) has special recognition selectivity and excellent binding affinity for
matrine. Relative to oxymatrine and cytisine, the selectivity coefficients of MIP
SAP/SiO(2) for matrine are 5.66 and 11.17, respectively.
PMID- 26426208
TI - Investigating the impact of pain, age, Gross Motor Function Classification
System, and sex on health-related quality of life in children with cerebral
palsy.
AB - AIM: To explore whether health-related quality of life (HRQOL) can be predicted
by pain, age, Gross Motor Function Classification System (GMFCS) level, and sex
in children with cerebral palsy (CP) and whether different pain etiologies have
varying effects on HRQOL. METHODS: Children with CP aged 3 to 19 years and their
caregivers were consecutively recruited. Caregivers reported their child's pain
(Health Utilities Index 3 [HUI3] pain subset) and HRQOL (DISABKIDS
questionnaires). Physicians identified pain etiologies. A multiple linear
regression model determined whether pain, GMFCS level, sex, and age predicted
HRQOL. An ANOVA evaluated the effects of pain etiologies on HRQOL. RESULTS: Three
hundred and forty-four participants were approached and 87% (n=300) participated.
Sufficient data were available on 248 (72% of total sample). Sixty-six
participants (27%) formed the pain group with HUI3 pain scores of at least 3. The
presence of pain and increasing age significantly negatively predicted HRQOL
(p<0.001, R(2) =0.141), while GMFCS and sex did not. Musculoskeletal deformity
(24%) and hypertonia (18%) were the most frequent pain causes. HRQOL
statistically differed depending on the pain etiology (p=0.028) with
musculoskeletal deformity showing the lowest mean HRQOL. INTERPRETATION: The
presence of pain and increasing age negatively predict HRQOL in CP.
musculoskeletal deformity has the greatest negative impact on HRQOL.
PMID- 26426209
TI - Protic Ionic Liquids: Evolving Structure-Property Relationships and Expanding
Applications.
PMID- 26426210
TI - Building intentions with the theory of planned behaviour: a qualitative
assessment of salient beliefs about pharmacy value added services in Malaysia.
AB - OBJECTIVE: To improve pharmaceutical care delivery in Malaysia, the Ministry of
Health (MOH) had introduced the concept of value added services (VAS). Despite
its reported convenience and advantages, VAS utilization rate is low in the
country. The study aims to explore patients' understanding, beliefs and
expectations towards VAS in Malaysia using the theory of planned behaviour (TPB)
as the theoretical model. METHODS: A qualitative methodology was used whereby
face-to-face interviews were conducted with 12 patients who collected partial
medicine supplies from government pharmacies. Participants were recruited using
purposive and snowball sampling method in the state of Negeri Sembilan, Malaysia.
Interviews were audio-recorded. Verbatim transcription and thematic content
analysis were performed on the data. RESULTS: Thematic content analysis yielded
five major themes: (i) attitudes towards using VAS, (ii) subjective norms, (iii)
perceived behavioural control, (iv) lack of knowledge and understanding of VAS
and (v) expectations towards VAS. CONCLUSION: The interviews explored and
informed new information about salient beliefs towards pharmacy VAS. The findings
suggest that VAS is still in its infancy and a more robust and effective
advertising and marketing campaign is needed to boost the adoption rate.
Behavioural attitudes, subjective norms and perceived control elements were
discussed and serve as important variables of interest in future study.
Expectations towards VAS serve as an important guideline to further improve
patient-oriented services.
PMID- 26426211
TI - OPG, RANKL, and RANK gene polymorphisms and the bone mineral density response to
alendronate therapy in postmenopausal Chinese women with osteoporosis or
osteopenia.
AB - OBJECTIVE: The aim of the study was to explore the association between OPG,
RANKL, and RANK gene variations and the bone mineral density (BMD) response to
alendronate therapy in postmenopausal Chinese women with osteoporosis or
osteopenia. MATERIALS AND METHODS: In the present study, 40 single-nucleotide
polymorphisms (SNPs) in the OPG, RANKL, and RANK genes were genotyped in 501
postmenopausal Chinese women with osteoporosis or osteopenia who were given
alendronate (70 mg weekly) orally for 1 year. The BMD at the lumbar spine 1-4 (L1
L4), femoral neck, and total hip was measured. RESULTS: A total of 442 patients
completed 1 year of alendronate therapy. The rs7239261 SNP of the RANK gene was
significantly associated with baseline L1-L4 BMD (P=0.0004) after correction for
age and BMI. Participants with the SNP A allele (C/A and A/A) had a higher BMD
than those with the C/C genotype (C/A vs. C/C, P=0.001; A/A vs. C/C, P=0.025).
Haplotypes AG of rs7239261-rs12969154, GG of rs3826619-rs11877530, and CACG of
rs1805034-rs8083511-rs17069895-rs7231887 in the RANK gene were genetic protective
factors toward a higher baseline L1-L4 BMD. No association was observed between
any SNP or haplotype of the OPG, RANKL, and RANK genes and the response of BMD to
alendronate therapy. CONCLUSION: The RANK gene might contribute to genetic
variability in L1-L4 BMD in postmenopausal Chinese women with osteoporosis or
osteopenia. No evidence of an association between any SNP or haplotype of the
OPG, RANKL, and RANK genes and the response of BMD to alendronate therapy was
found in postmenopausal Chinese women with osteoporosis or osteopenia.
PMID- 26426212
TI - A genetic variant in NRP1 is associated with worse response to ranibizumab
treatment in neovascular age-related macular degeneration.
AB - OBJECTIVE: The aim of the study was to investigate the role of single-nucleotide
polymorphisms (SNPs) located in the neuropilin-1 (NRP1) gene in treatment
response to antivascular endothelial growth factor (VEGF) therapy for neovascular
age-related macular degeneration (nvAMD). METHODS: Four SNPs in the NRP1 gene
(rs2229935, rs2247383, rs2070296, and rs2804495) were genotyped in a study cohort
of 377 nvAMD patients who received the loading dose of three monthly ranibizumab
injections. Treatment response was assessed as the change in visual acuity after
three monthly loading injections compared with baseline. RESULTS: SNP rs2070296
was associated with change in visual acuity after 3 months of treatment. Patients
carrying the GA or AA genotypes performed significantly worse than individuals
carrying the GG genotype (P=0.01). A cumulative effect of rs2070296 in the NRP1
gene and rs4576072 located in the VEGF receptor 2 (VEGFR2 or KDR) gene,
previously associated with treatment response, was observed. Patients carrying
two risk alleles performed significantly worse than patients carrying zero or one
risk allele (P=0.03), and patients with more than two risk alleles responded even
worse to the therapy (P=3*10). The combined effect of these two SNPs on the
response was also seen after 6 and 12 months of treatment. CONCLUSION: This study
suggests that genetic variation in NRP1, a key molecule in VEGFA-driven
neovascularization, influences treatment response to ranibizumab in nvAMD
patients. The results of this study may be used to generate prediction models for
treatment response, which in the future may help tailor medical care to
individual needs.
PMID- 26426215
TI - Integrating Tobacco Use Treatment Into Practice: Billing and Documentation.
AB - Balancing population-based efforts to modify the social and environmental factors
that promote tobacco dependence with efforts to improve the delivery of case
based treatments is necessary for realizing maximum reductions in the cost and
consequences of the disease. Public health antismoking campaigns following the
1964 Surgeon General's report on the health risks of smoking have changed social
norms, prevented initiation among youth, and promoted abstinence among the
addicted. However, the rate of progress enjoyed to date is unlikely to continue
into the coming decades, given that current annual unassisted cessation rates
among prevalent smokers remains fairly low. With more than 1 billion patient
interactions annually, there is an enormous unrealized capacity for health-care
systems to have an effect on this problem. Clinicians report a perceived lack of
reimbursement as a significant barrier to full integration of tobacco dependence
into health care. A more complete understanding of the coding and documentation
requirements for successful practice in this critically important area is a
prerequisite to increasing engagement. This paper presents several case-based
scenarios illustrating important practice management issues related to the
treatment of tobacco dependence in health care.
PMID- 26426216
TI - Association between the diagnosis of atrial fibrillation and aspects of health
status: a Danish cross-sectional study.
AB - BACKGROUND: Caring for patients living with atrial fibrillation (AF) is expected
to be an increasing challenge for the healthcare sector in the future.
Inconclusive results on self-reported health-related quality of life and health
status in patients living with AF have previously been reported, ranging from
being similar to those observed in patients who have sustained and survived a
myocardial infarction to not being different from those of healthy subjects. In
these studies, gender differences were not taken into account. AIM AND OBJECTIVE:
To investigate the association between the diagnosis of atrial fibrillation and
self-reported health status. DESIGN: An observational, cross-sectional study was
conducted using data from the Danish Diet, Cancer and Health cohort. Information
on health status was obtained using the Danish version of the Short Form 36
version 2 questionnaire. The analyses were stratified on gender. In adjusted
analysis, we considered potential confounding from comorbidity expressed by the
Charlson Comorbidity Index and effect modification by age. ETHICAL APPROVAL: The
local ethical committees of Copenhagen and Frederiksberg municipalities (Approval
no.: (KF) 01-345/93) approved the study. RESULTS: We included 42 598 participants
of whom 873 had a diagnosis of AF and/or atrial flutter. We found a lower
adjusted physical component score among AF patients. No systematic differences in
the mental component score (MCS) were observed. CONCLUSION: Participants
diagnosed with AF report a clinically and statistically significantly lower
physical health component score. No systematic differences in the MCS were found
when comparing with the remaining participants in the cohort. As healthcare
professionals caring for patients living with AF are not always expecting
patients living with AF to experience a burden from their disease, the individual
patients' experience of their situation, feelings, preferences, symptoms and
needs leading to physical limitations should always be articulated.
PMID- 26426229
TI - For All Intensive Purposes.
PMID- 26426217
TI - Seroprevalence of Babesia microti infection in Canadian blood donors.
AB - BACKGROUND: Human babesiosis, caused by the intraerythrocytic protozoan parasite
Babesia microti, is primarily transmitted by tick bites and is also transmitted
by transfusion. Infections have been identified in U.S. blood donors close to
Canadian borders. We aimed to assess the risk of transfusion-transmitted
babesiosis in Canada by examining infections in ticks and seroprevalence in blood
donors. STUDY DESIGN AND METHODS: Passive surveillance (receipt of ticks
submitted by the public) was used to identify regions for tick drag sampling
(active surveillance, 2009-2014). All ticks were tested for B. microti using an
indirect immunofluorescent antibody assay (Imugen, Inc.). Between July and
December 2013, blood donations from selected sites (southern Manitoba, Ontario,
Quebec, New Brunswick, and Nova Scotia) near endemic U.S. regions were tested for
antibody to B. microti. Donors completed a questionnaire about risk travel and
possible tick exposure. RESULTS: Of approximately 12,000 ticks submitted, 14 were
B. microti positive (10 in Manitoba, one in Ontario, one in Quebec, two in New
Brunswick). From active tick surveillance, six of 361 ticks in Manitoba were
positive (1.7%), three of 641 (0.5%) in Quebec, and none elsewhere. There were
26,260 donors at the selected sites of whom 13,993 (53%) were tested. None were
positive for antibody to B. microti. In 2013, 47% of donors visited forested
areas in Canada, and 41% traveled to the United States. CONCLUSION: The data do
not suggest that laboratory-based testing is warranted at this time. However,
there are indicators that B. microti may be advancing into Canada and ongoing
monitoring of tick populations and donor seroprevalence is indicated.
PMID- 26426230
TI - Diagnosis and Management of Subarachnoid Hemorrhage.
AB - PURPOSE OF REVIEW: The purpose of this article is to present the epidemiology,
clinical presentation, and management of patients with subarachnoid hemorrhage
(SAH). SAH is a neurologic emergency that carries high morbidity and mortality.
Patients with SAH are at risk for several significant neurologic complications,
including hydrocephalus, cerebral edema, delayed cerebral ischemia, rebleeding,
seizures, and neuroendocrine abnormalities that lead to impaired body regulation
of sodium, water, and glucose. RECENT FINDINGS: The incidence of SAH has remained
stable, but mortality of hospitalized patients has significantly declined over
the past 3 decades. Many common therapies for SAH have created controversy, and
various recent neuroprotective clinical trials have produced negative results.
However, the publication of two consensus guidelines by the American Heart
Association/American Stroke Association and the Neurocritical Care Society have
provided a clarification for what should constitute best practice for patients
with SAH. The most important of those recommendations include the following:
admission of patients to high-volume centers (defined as more than 35 patients
with SAH per year) under the management of a specialized and multidisciplinary
team; early identification and management of the bleeding source; evaluation and
treatment decision for unsecured aneurysms by a multidisciplinary team made up of
cerebrovascular neurosurgeons, endovascular practitioners, and neurointensivists;
management of patients in the neurocritical care unit with oral nimodipine, blood
pressure control, euvolemia, and frequent monitoring for neurologic and systemic
complications; and delayed cerebral ischemia secondary to cerebral vasospasm
should be treated with induced hypertension and endovascular therapies once
confirmed. SUMMARY: SAH is a devastating neurologic disease. Management of
patients with SAH should adhere to currently available treatment guidelines.
Several aspects of SAH management remain controversial and need further studies
to clarify their role in improving patient outcome.
PMID- 26426231
TI - Diagnosis and Management of Spontaneous Intracerebral Hemorrhage.
AB - PURPOSE OF REVIEW: This article updates neurologists on recent insights and
management strategies of intracerebral hemorrhage (ICH). RECENT FINDINGS: Blood
pressure reduction likely improves outcomes in patients with intracerebral
hemorrhage, although not by the expected mechanism of reducing hematoma growth.
One formulation of prothrombin complex concentrate for reversing severe bleeding
associated with warfarin is now approved by the US Food and Drug Administration
(FDA), and specific reversal therapies for the novel oral anticoagulants are in
development. Neurologic monitoring frequently detects ICH worsening that requires
an intervention. Platelet transfusion and pharmacologic platelet activation are
promising and often used as part of patient management but have not yet been
shown to improve patient outcomes. SUMMARY: Measurable progress continues toward
establishing effective therapies to improve outcomes in patients with ICH. Blood
pressure reduction and reversal of medications that exacerbate bleeding are
likely to improve outcomes. Recommendations for neuromonitoring will help
clinicians at the bedside attend to the most important abnormalities and optimize
later quality of life. This article reviews standards for diagnosis and severity
of ICH, monitoring and treatment of complications in the hospital, available
interventions, and the measurement of outcomes.
PMID- 26426232
TI - Management of Intracranial Pressure.
AB - PURPOSE OF REVIEW: Intracranial pressure (ICP) can be elevated in traumatic brain
injury, large artery acute ischemic stroke, intracranial hemorrhage, intracranial
neoplasms, and diffuse cerebral disorders such as meningitis, encephalitis, and
acute hepatic failure. Raised ICP is also known as intracranial hypertension and
is defined as a sustained ICP of greater than 20 mm Hg. RECENT FINDINGS: ICP must
be measured through an invasive brain catheter, typically an external ventricular
catheter that can drain CSF and measure ICP, or through an intraparenchymal ICP
probe. Proper recognition of the clinical signs of elevated ICP is essential for
timely diagnosis and treatment to prevent cerebral hypoperfusion and possible
brain death. Clinical signs of elevated ICP include headache, papilledema,
nausea, and vomiting in the early phases, followed by stupor and coma, pupillary
changes, hemiparesis or quadriparesis, posturing and respiratory abnormalities,
and eventually cardiopulmonary arrest. SUMMARY: Management of elevated ICP is, in
part, dependent on the underlying cause. Medical options for treating elevated
ICP include head of bed elevation, IV mannitol, hypertonic saline, transient
hyperventilation, barbiturates, and, if ICP remains refractory, sedation,
endotracheal intubation, mechanical ventilation, and neuromuscular paralysis.
Surgical options include CSF drainage if hydrocephalus is present and
decompression of a surgical lesion, such as an intracranial hematoma/large
infarct or tumor, if the patient's condition is deemed salvageable. Future
research should continue investigating medical and surgical options for the
treatment of raised ICP, such as hypothermia, drugs that reduce cerebral edema,
and operations aimed at reducing intracranial mass effect.
PMID- 26426233
TI - Acute Neuromuscular Respiratory Failure.
AB - PURPOSE OF REVIEW: Neurologists working in the hospital are often called to
evaluate patients with severe muscle weakness. Some of these patients can develop
ventilatory compromise and require admission to the intensive care unit (ICU).
This article reviews the general evaluation of neuromuscular respiratory failure,
discusses its differential diagnosis, and provides practical advice on the
management of its most common causes. RECENT FINDINGS: Determining the cause of
acute neuromuscular respiratory failure is crucial because functional prognosis
is poor in patients for whom the cause cannot be defined. The differential
diagnosis is extensive, but the first step is to discriminate between cases
related to a primary neurologic disease (primary neuromuscular respiratory
failure) and those provoked by systemic disease, most often critical illness from
sepsis and multiorgan failure (secondary neuromuscular respiratory failure).
Guillain-Barre syndrome (GBS) and myasthenic crisis are the two most frequent
causes of primary neuromuscular respiratory failure. Although they are both
autoimmune conditions that benefit from the administration of plasma exchange or
IV immunoglobulin (IVIg), they are otherwise very different disorders with unique
features and distinct complications. Optimal strategies for mechanical
ventilation also differ between these two conditions; while myasthenic crisis is
ideally managed with noninvasive bilevel positive airway pressure (BiPAP)
ventilation, GBS demands early intubation. SUMMARY: Prompt recognition of
neuromuscular respiratory failure can be lifesaving, and identification of its
cause has substantial prognostic implications. Adequate management of these
patients requires a multidisciplinary team with the neurologist at its center,
not only to guide the diagnostic evaluation but often also to prescribe the
optimal management.
PMID- 26426234
TI - Management of Hemispheric Infarction and Ischemic Swelling.
AB - PURPOSE OF REVIEW: This article provides an overview of large territory
hemispheric infarction, with an emphasis on recent developments and practical
issues related to its evaluation, diagnosis, monitoring, and treatment. Swelling
after large infarction results in severe morbidity and often death. Early
vigilance for the development of swelling is critical to optimize patient
outcome. Comprehensive management is highly dependent on a strong
multidisciplinary, collaborative approach. RECENT FINDINGS: Several advances in
the last decade have led to an increasingly standardized approach to the patient
with significant brain swelling after stroke. In particular, early identification
of patients with large stroke at high risk for deterioration, and decompressive
craniectomy as an important treatment option, are two significant advances.
SUMMARY: Effective management of hemispheric ischemic stroke and swelling
requires a team skilled in the neurologic examination of critically ill patients
and a broad understanding of the natural history of brain swelling after stroke.
PMID- 26426235
TI - Status Epilepticus.
AB - PURPOSE OF REVIEW: Status epilepticus, which is simultaneously a neurologic and
systemic emergency, often results in significant disability and may be fatal.
This article presents a pragmatic approach to the evaluation and management of
status epilepticus in adults for the practicing clinician. RECENT FINDINGS: Rapid
recognition, treatment respecting a written protocol, and careful attention to
potential complications may limit sequelae. Studies aimed at earlier
identification of etiologies in cryptogenic status epilepticus and improving the
treatment of established status epilepticus are urgently needed to limit the
development of refractoriness. SUMMARY: This article reviews the guidelines and
up-to-date information on the use of both pharmacologic and nonpharmacologic
therapies in status epilepticus and discusses the shifts in our understanding of
the balance between the need for aggressive control of seizures and the risks of
treatment. This article also presents a suggested approach to the evaluation and
management of common types of status epilepticus and explores future directions.
PMID- 26426236
TI - Cardiac Arrest and Postanoxic Encephalopathy.
AB - PURPOSE OF REVIEW: Neuroprognostication following cardiac arrest is a common and
challenging dilemma for neurologists and intensivists, complicated by the use of
therapeutic hypothermia and targeted temperature management. Great advances have
been made in understanding the mechanisms of disorders of consciousness in
hypoxic-ischemic brain injury, and new diagnostic and therapeutic avenues are
arising. RECENT FINDINGS: In the era of therapeutic hypothermia and targeted
temperature management, traditional clinical signs, electrophysiologic findings,
and chemical biomarkers have now become questionable or variable, and the proper
time for diagnostic and prognostic testing has become murky. Although the value
of absent pupillary and corneal reflexes remains fairly robust, the presence of
myoclonic status epilepticus and a motor response of extensor posturing or worse
no longer appear to have acceptable false-positive rates. Somatosensory evoked
potentials (SSEPs), thought to be the most reliable ancillary test for predicting
prognosis, have recently been the subject of several reports showing unexpectedly
good outcome in the face of absent cortical responses. The presence or absence of
reactivity on EEG appears to be a promising prognostic sign, and aggressive
treatment of seizures (and even status epilepticus) may lead to better than
expected outcomes. Serum biomarkers that were previously felt to be valid, such
as elevated neuron-specific enolase, have been drawn into question owing to
multiple reports of patient survival with good outcome despite highly elevated
levels. Advanced EEG and neuroimaging techniques, particularly looking at
functional connectivity and underlying neuronal pathways, are giving great
insights to the underlying mechanisms of disease and potential therapeutic
targets. SUMMARY: Predicting neurologic prognosis following cardiac arrest is an
evolving field, with new prognostic methods and reevaluation of older techniques
holding great promise for advancing our ability to predict outcome and improve
patient care.
PMID- 26426237
TI - Evaluating the Potential for Recovery of Consciousness in the Intensive Care
Unit.
AB - PURPOSE OF REVIEW: Evaluating patients in the intensive care unit (ICU) with
disorders of consciousness has prognostic implications. When brainstem functions
are intact, the neurologist must use ancillary testing to help determine
prognosis. This article addresses the challenges of arriving at prognoses in
patients with hypoxic-ischemic encephalopathy and traumatic brain injury (TBI)
and discusses strategies for dealing with these challenges. This has some
relevance to other conditions that are capable of causing irreversible brain
damage. RECENT FINDINGS: Although practice parameters formulated by an American
Academy of Neurology (AAN) subcommittee in 2006 were reliable for evaluating
patients with hypoxic-ischemic encephalopathy who did not receive hypothermia,
the advent of hypothermia has shown that some of these prognostic features were
unreliable. Some patients with TBI thought to be vegetative have been found to
have cognitive responses. These revelations require neurologists to reconsider
prognostic strategies. SUMMARY: To arrive at a more accurate prognosis, it is
best to employ multiple pieces of evidence and incorporate the most updated
information from the literature. In some cases, newer technologies can provide
further insights into cortical function in behaviorally unresponsive patients.
PMID- 26426238
TI - Determining Brain Death.
AB - PURPOSE OF REVIEW: Major complexities exist in the assessment of a patient with a
catastrophic neurologic disorder that might have progressed to loss of all brain
function. The determination of brain death and initial management of the
potential organ donor is one of the major key tasks of the neurologist. This
article addresses the potential for errors, mimickers, and uncertainties
associated with ancillary tests for determining brain death. RECENT FINDINGS:
Major professional neurologic organizations including the American Academy of
Neurology have published guidelines for the determination of brain death in both
adults and children. Checklists are now available to assist physicians in the
assessment of the patient. SUMMARY: The clinical diagnosis of brain death in a
patient with a catastrophic brain injury is determined by a comprehensive
clinical examination that involves at least 25 individual assessments. It
requires excluding confounding factors first (to confirm futility), examining the
patient carefully with special attention to signs of brainstem function, and,
finally, performing an apnea test. Once a patient is declared brain dead, organ
donation may proceed after consent is obtained.
PMID- 26426239
TI - Complications of Neurosurgery.
AB - PURPOSE OF REVIEW: This article provides an overview of the major neurologic
complications of common neurosurgical and endovascular procedures. RECENT
FINDINGS: Brain edema, seizures, postoperative hemorrhage, and cerebral ischemia
can complicate neurosurgical procedures and produce neurologic decline. The high
variability of reporting, types of operations, patient characteristics, and
acuity of cases make estimating the incidence and severity of complications
difficult. Overall, the complication rate of neurosurgical procedures is
approximately 14%, but these are commonly systemic complications (eg, bleeding
requiring transfusion, need for mechanical ventilation). In addition to
intracranial hemorrhage, ischemia, and seizures after craniotomies, additional
characteristic complications include hyperperfusion syndrome and cranial nerve
palsies after carotid endarterectomy, cerebrospinal fluid leaks and aseptic
meningitis after posterior fossa surgery, and arterial dissections or groin
hematomas after endovascular procedures. SUMMARY: Neurologic decline can be
caused by a variety of causes in the postoperative period. The indication for
surgery, type of surgery, and time of decline is helpful in narrowing the
differential diagnosis. Brain edema, elevated intracranial pressure (ICP),
seizures, intracranial hemorrhage, ischemic infarction, and cranial nerve palsies
are some of the more common complications in patients that neurologists may be
asked to evaluate or comanage in the postoperative setting.
PMID- 26426240
TI - Ethical Aspects of Organ Donation After Circulatory Death.
AB - Neurologists should be familiar with the process and ethical aspects of organ
donation. While most neurologists understand the steps involved in organ
procurement following brain death, the controversial practice of organ donation
after circulatory death (also referred to as non-heart-beating organ donation) is
less familiar but increasingly frequent. This article presents a hypothetical
case of a patient with a devastating neurologic injury and a poor prognosis for
meaningful recovery and discusses the ethical considerations underlying donation
after circulatory death, the general procedure of donation after circulatory
death, and ethical controversies associated with this practice.
PMID- 26426241
TI - Advanced Practice Provider Utilization in the Neurocritical Care Unit.
AB - This article discusses the role of advanced practice providers (APPs) in the
interprofessional team management of patients with critical neurologic illnesses
and how this role has evolved through the years. There is increasing demand for
these types of practitioners, formerly termed midlevel providers. Furthermore,
the use of APPs appears to have a positive impact on patient satisfaction,
reduced costs, and reduced length of stays.
PMID- 26426242
TI - Critical Care Coding for Neurologists.
AB - Accurate coding is an important function of neurologic practice. This
contribution to Continuum is part of an ongoing series that presents helpful
coding information along with examples related to the issue topic. Tips for
diagnosis coding, Evaluation and Management coding, procedure coding, or a
combination are presented, depending on which is most applicable to the subject
area of the issue.
PMID- 26426247
TI - Patient Management Problem.
PMID- 26426250
TI - Next-Generation Sequencing for the Identification of Targetable Molecular
Alterations in Cancer.
PMID- 26426252
TI - A strategy for reducing neonatal mortality at high altitude using oxygen
conditioning.
AB - Neonatal mortality increases with altitude. For example, in Peru the incidence of
neonatal mortality in the highlands has been shown to be about double that at
lower altitudes. An important factor is the low inspired PO2 of newborn babies.
Typically, expectant mothers at high altitude will travel to low altitude to have
their babies if possible, but often this is not feasible because of economic
factors. The procedure described here raises the oxygen concentration in the air
of rooms where neonates are being housed and, in effect, this means that both the
mother and baby are at a much lower altitude. Oxygen conditioning is similar to
air conditioning except that the oxygen concentration of the air is increased
rather than the temperature being reduced. The procedure is now used at high
altitude in many hotels, dormitories and telescope facilities, and has been shown
to be feasible and effective.
PMID- 26426251
TI - Cancer-Cell-Specific Nuclear-Targeted Drug Delivery by Dual-Ligand-Modified
Mesoporous Silica Nanoparticles.
AB - Mesoporous silica nanoparticles are modified with dual targeting ligands, i.e.,
folic acid and dexamethasone, to construct a cancer-cell-specific nuclear
targeted delivery system. The resulting nanocarriers can not only enhance the
inhibition efficacy of doxorubicin on Hela cells through active nucleus
accumulation but also reduce toxic side effects on noncancer cells though
receptor-mediated selective cellular uptake.
PMID- 26426254
TI - Palladium-catalyzed three-component reaction of N-tosyl hydrazones, isonitriles
and amines leading to amidines.
AB - A palladium-catalyzed three-component reaction between N-tosyl hydrazones, aryl
isonitriles and amines was developed, leading to amidines in moderate to good
yields. This procedure features the rapid construction of amidine frameworks with
high diversity and complexity. Ketenimines serve as intermediates, which
encounter nucleophilic attack by amines to produce amidines.
PMID- 26426253
TI - Proton magnetic resonance spectroscopy and outcome in term neonates with
chorioamnionitis.
AB - OBJECTIVE: Evaluate brain metabolites, which reflect neuroinflammation, and
relate to neurodevelopmental outcomes in healthy term neonates exposed to
chorioamnionitis. STUDY DESIGN: Thirty-one healthy term neonates with documented
fetal inflammatory response after maternal chorioamnionitis underwent magnetic
resonance spectroscopy (MRS), with voxels placed in basal ganglia (BG) and
frontal white matter. Bayley III examinations were performed at 12 months of age.
RESULT: Infants with below average outcomes did not show the same increase in
NAA/Cho ratios postnatally as the group with normal outcomes. Decreased NAA/Cho
and increased Lac/Cr in BG correlated with lower motor and cognitive composite
scores, respectively, controlling for postnatal age. In males, increased
lactate/NAA in BG were associated with lower motor scores. Funisitis severity was
associated with decreased NAA/Cho and increased mI/NAA in males. CONCLUSION: In
healthy term newborns with chorioamnionitis, MRS ratios shortly after birth may
provide evidence of occult neuroinflammation, which may be associated with worse
performance on 1-year neurodevelopmental tests.
PMID- 26426255
TI - Reprogramming of macrophages--new opportunities for therapeutic targeting.
AB - Macrophages are key players of tissue homeostasis and are cells involved in all
major human diseases including infections, tumors, western life-style associated
diseases and even neurodegenerative diseases. Therefore, specifically targeting
macrophages seems to be an attractive therapeutic approach, yet such strategies
have not been successfully translated to the clinic. An important hallmark of
macrophages is their astounding plasticity and their capacity to integrate
microenvironmental signals to perform distinct biological functions.
Understanding the cellular programming of macrophages during such events will be
a fundamental pre-requisite to develop targeted therapeutic approaches in human
diseases. Here, I highlight recent findings of how macrophage activation is
regulated and how one can envision much more specific approaches of targeting
macrophages.
PMID- 26426257
TI - Brassinin Combined with Capsaicin Enhances Apoptotic and Anti-metastatic Effects
in PC-3 Human Prostate Cancer Cells.
AB - Brassinin (BSN), a type of indole compound derived from cruciferous vegetables,
has shown anti-cancer effects in cells and animals. Capsaicin (CAP), an alkaloid
derived from the chilli pepper, is also of interest in for its reported efficacy
against various malignancies. The objective of our study was to analyze the
potential synergistic anti-tumor effects of BSN combined with CAP on prostate
cancer PC-3 cells. After treatment with BSN and CAP at various concentrations,
the synergistic cytotoxic effect of PC-3 cells was analyzed by MTT method,
proliferation, apoptosis, mitochondrial membrane potential, colony formation, and
Western blotting. Moreover, the inhibitory effects of BSN and CAP on the
constitutive expressions of MMP-9/2, their enzymatic activities, cellular
migration, and cell invasion were also investigated. The cytotoxicity was
synergistically increased in combination compared with the single drug used;
moreover, proliferation, apoptosis, mitochondrial membrane potential, and colony
formation were significantly suppressed and anti-apoptotic-, proliferative-, and
metastatic-related proteins were clearly abolished in the combination group.
Besides, constitutive MMP-9/2 expression, their enzymatic activities, cell
migration, and tumor cell invasion were inhibited, and TIMP-1 was up-regulated in
the combination group in PC-3 cells. Our results indicate, for the first time,
that BSN and CAP in combination exert synergistic anticancer effects in prostate
carcinoma.
PMID- 26426256
TI - Potassium inhibits nitric oxide and adenosine arteriolar vasodilatation via K(IR)
and Na(+)/K(+) ATPase: implications for redundancy in active hyperaemia.
AB - Redundancy, in active hyperaemia, where one vasodilator can compensate for
another if the first is missing, would require that one vasodilator inhibits the
effects of another; therefore, if the first vasodilator is inhibited, its
inhibitory influence on the second vasodilator is removed and the second
vasodilator exerts a greater vasodilatory effect. We aimed to determine whether
vasodilators relevant to skeletal muscle contraction [potassium chloride (KCl),
adenosine (ADO) and nitric oxide] inhibit one another and, in addition, to
investigate the mechanisms for this interaction. We used the hamster cremaster
muscle and intravital microscopy to directly visualize 2A arterioles when exposed
to a range of concentrations of one vasodilator [10(-8) to 10(-5) M S-nitroso-N
acetyl penicillamine (SNAP), 10(-8) to 10(-5) M ADO, 10 and 20 mM KCl] in the
absence and then in the presence of a second vasodilator (10(-7) M ADO, 10(-7) M
SNAP, 10 mM KCl). We found that KCl significantly attenuated SNAP-induced
vasodilatations by ~65.8% and vasodilatations induced by 10(-8) to 10(-6) M ADO
by ~72.8%. Furthermore, we observed that inhibition of KCl vasodilatation, by
antagonizing either Na(+)/K(+) ATPase using ouabain or inward rectifying
potassium channels using barium chloride, could restore the SNAP-induced
vasodilatation by up to ~53.9% and 30.6%, respectively, and also restore the ADO
induced vasodilatations by up to ~107% and 76.7%, respectively. Our data show
that vasodilators relevant to muscle contraction can interact in a way that
alters the effectiveness of other vasodilators. These data suggest that active
hyperaemia may be the result of complex interactions between multiple
vasodilators via a redundant control paradigm.
PMID- 26426258
TI - Neurodegeneration in Autoimmune Optic Neuritis Is Associated with Altered APP
Cleavage in Neurons and Up-Regulation of p53.
AB - Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the
central nervous system (CNS). Histopathological and radiological analysis
revealed that neurodegeneration occurs early in the disease course. However, the
pathological mechanisms involved in neurodegeneration are poorly understood.
Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune
encephalomyelitis (EAE) in Brown Norway rats (BN-rats) is a well-established
animal model, especially of the neurodegenerative aspects of MS. Previous studies
in this animal model indicated that loss of retinal ganglion cells (RGCs), the
neurons that form the axons of the optic nerve, occurs in the preclinical phase
of the disease and is in part independent of overt histopathological changes of
the optic nerve. Therefore, the aim of this study was to identify genes which are
involved in neuronal cell loss at different disease stages of EAE. Furthermore,
genes that are highly specific for autoimmune-driven neurodegeneration were
compared to those regulated in RGCs after optic nerve axotomy at corresponding
time points. Using laser capture micro dissection we isolated RNA from unfixed
RGCs and performed global transcriptome analysis of retinal neurons. In total, we
detected 582 genes sequentially expressed in the preclinical phase and 1150 genes
in the clinical manifest EAE (P < 0.05, fold-induction >1.5). Furthermore, using
ingenuity pathway analysis (IPA), we identified amyloid precursor protein (APP)
as a potential upstream regulator of changes in gene expression in the
preclinical EAE but neither in clinical EAE, nor at any time point after optic
nerve transection. Therefore, the gene pathway analysis lead to the hypothesis
that altered cleavage of APP in neurons in the preclinical phase of EAE leads to
the enhanced production of APP intracellular domain (AICD), which in turn acts as
a transcriptional regulator and thereby initiates an apoptotic signaling cascade
via up-regulation of the target gene p53.
PMID- 26426259
TI - TRPM8-Dependent Dynamic Response in a Mathematical Model of Cold Thermoreceptor.
AB - Cold-sensitive nerve terminals (CSNTs) encode steady temperatures with regular,
rhythmic temperature-dependent firing patterns that range from irregular tonic
firing to regular bursting (static response). During abrupt temperature changes,
CSNTs show a dynamic response, transiently increasing their firing frequency as
temperature decreases and silencing when the temperature increases (dynamic
response). To date, mathematical models that simulate the static response are
based on two depolarizing/repolarizing pairs of membrane ionic conductance (slow
and fast kinetics). However, these models fail to reproduce the dynamic response
of CSNTs to rapid changes in temperature and notoriously they lack a specific
cold-activated conductance such as the TRPM8 channel. We developed a model that
includes TRPM8 as a temperature-dependent conductance with a calcium-dependent
desensitization. We show by computer simulations that it appropriately reproduces
the dynamic response of CSNTs from mouse cornea, while preserving their static
response behavior. In this model, the TRPM8 conductance is essential to display a
dynamic response. In agreement with experimental results, TRPM8 is also needed
for the ongoing activity in the absence of stimulus (i.e. neutral skin
temperature). Free parameters of the model were adjusted by an evolutionary
optimization algorithm, allowing us to find different solutions. We present a
family of possible parameters that reproduce the behavior of CSNTs under
different temperature protocols. The detection of temperature gradients is
associated to a homeostatic mechanism supported by the calcium-dependent
desensitization.
PMID- 26426261
TI - Squaraine based solution processed inverted bulk heterojunction solar cells
processed in air.
AB - Inverted bulk heterojunction solar cells based on low temperature solution
processed squaraine (SQ) and [6,6]-phenyl C71 butyric acid methyl-ester (PC71BM)
with varying blend ratios were made in air. An optimized bulk heterojunction
device of SQ and PC71BM (with a blend ratio of 1 : 6) showed a power conversion
efficiency (PCE) of 2.45% with an incident photon to current conversion
efficiency of 65% at 680 nm and a spectral window extending to the NIR region.
The devices also showed an enhanced PCE value of 4.12% upon continuous
illumination from an AM1.5G light source of intensity 1 Sun. The intensity
dependent photocurrent studies showed a monomolecular recombination mechanism in
the photovoltaic device performance. The device stored in air showed reasonable
stability for a period of one month.
PMID- 26426262
TI - Si Donor Incorporation in GaN Nanowires.
AB - With increasing interest in GaN based devices, the control and evaluation of
doping are becoming more and more important. We have studied the structural and
electrical properties of a series of Si-doped GaN nanowires (NWs) grown by
molecular beam epitaxy (MBE) with a typical dimension of 2-3 MUm in length and 20
200 nm in radius. In particular, high resolution energy dispersive X-ray
spectroscopy (EDX) has illustrated a higher Si incorporation in NWs than that in
two-dimensional (2D) layers and Si segregation at the edge of the NW with the
highest doping. Moreover, direct transport measurements on single NWs have shown
a controlled doping with resistivity from 10(2) to 10(-3) Omega.cm, and a carrier
concentration from 10(17) to 10(20) cm(-3). Field effect transistor (FET)
measurements combined with finite element simulation by NextNano(3) software have
put in evidence the high mobility of carriers in the nonintentionally doped (NID)
NWs.
PMID- 26426260
TI - Transcriptomic Analysis of Ovaries from Pigs with High And Low Litter Size.
AB - Litter size is one of the most important economic traits for pig production as it
is directly related to the production efficiency. Litter size is affected by
interactions between multiple genes and the environment. While recent studies
have identified some genes associated with prolificacy in pigs, transcriptomic
studies of specific genes affecting litter size in porcine ovaries are rare. In
order to identify candidate genes associated with litter size in swine, we
assessed gene expression differences between the ovaries of Yorkshire pigs with
extremely high and low litter sizes using the RNA-Seq method. A total of 1 243
differentially expressed genes were identified: 897 genes were upregulated and
346 genes were downregulated in high litter size ovary samples compared with low
litter size ovary samples. A large number of these genes related to steroid
hormone regulation in animal ovaries, including 59 Gene Ontology terms and 27
Kyoto Encyclopedia of Genes and Genomes pathways involved in steroid biosynthesis
and ovarian steroidogenesis. From these differentially expressed genes, we
identified a total of 11 genes using a bioinformatics screen that may be
associated with high litter size in Yorkshire pigs. These results provide a list
of new candidate genes for porcine litter size and prolificacy to be further
investigated.
PMID- 26426263
TI - Anti-inflammatory role of obestatin in autoimmune myocarditis.
AB - Obestatin is a popular endogeneous peptide, known to have an autoimmune
regulatory effect on energy metabolism and the gastrointestinal system. Studies
regarding the anti-inflammatory effects of obestatin are scarce. The aim of this
study was to show the anti-inflammatory effect of obestatin in an experimental
model of autoimmune myocarditis in rats. Experimental autoimmune myocarditis was
induced in Lewis rats by immunization with subcutaneous administration of porcine
cardiac myosin, twice at 7-day intervals. Intraperitoneal pretreatment with
obestatin (50 MUg/kg) was started before the induction of myocarditis and
continued for 3 weeks. The severity of myocarditis was evidenced by clinical,
echocardiographic and histological findings. In addition, by-products of
neutrophil activation, lipid peroxidation, inflammatory and anti-inflammatory
cytokines were measured in serum. Obestatin significantly ameliorated the
clinical and histopathological severity of autoimmune myocarditis. Therapeutic
effects of obestatin in myocarditis were associated with reduced lipid
peroxidation, suppression of polymorphonuclear leukocyte infiltration and
enhancement of glutathione synthesis, inhibition of serum inflammatory and
activation of anti-inflammatory cytokines. Histopathologically, the left
ventricle was significantly dilated, and its wall thickened, along with
widespread lymphocytic and histocytic infiltration. The myocardium was severely
infiltrated with relatively large mononuclear cells. These histopathological
changes were observed in lesser degrees in obestatin-treated rats. This study
demonstrated a novel anti-inflammatory effect of obestatin in an experimental
model of autoimmune myocarditis. Consequently, obestatin administration may
represent a promising therapeutic approach for myocarditis and dilated
cardiomyopathy in the future.
PMID- 26426264
TI - A Quinoline Carboxamide Antimalarial Drug Candidate Uniquely Targets Plasmodia at
Three Stages of the Parasite Life Cycle.
PMID- 26426265
TI - A 15-year retrospective analysis of prognostic factors in childhood bacterial
meningitis.
AB - AIM: This retrospective chart review aimed to identify factors in childhood
bacterial meningitis that predicted disease severity and long-term outcome.
METHODS: The study included 112 episodes of microbiologically confirmed bacterial
meningitis in children aged three days to 15 years who were admitted to a
Singapore hospital from 1998 to 2013. RESULTS: The mortality rate was 6%, and 44%
required intensive care unit (ICU) admission. Predictive factors associated with
ICU admission included pneumococcal meningitis, with an odds ratio (OR) of 5.2
and 95% confidence interval (CI) of 1.5-18.2, leukopenia (OR 5.6, 95% CI 1.7
17.9) and a cerebrospinal fluid (CSF):serum glucose ratio <0.25 (OR 4.5, 95% CI
1.4-14.4). An initial CSF white blood cell count >1000/mm(3) (OR 0.26, 95% CI
0.086-0.76) was negatively associated with ICU admission. Five years after
meningitis, 32% had residual sequelae, and the associated prognostic factors were
Haemophilus influenzae type b (Hib) meningitis (OR 29.5, 95% CI 2-429), seizures
during their inpatient stay (OR 10.6, 95% CI 1.9-60.2) and septic shock (OR 8.4,
95% CI 1.1-62.1). CONCLUSION: As mortality was low in this bacterial meningitis
study, ICU admission was used as a marker of disease severity. These findings
underscore the importance of the pneumococcal and Hib meningitis vaccines.
PMID- 26426266
TI - A Novel Tau Mutation in Exon 12, p.Q336H, Causes Hereditary Pick Disease.
AB - Pick disease (PiD) is a frontotemporal lobar degeneration with distinctive
neuronal inclusions (Pick bodies) that are enriched in 3-repeat (3R) tau.
Although mostly sporadic, mutations in the tau gene (MAPT) have been reported. We
screened 24 cases of neuropathologically confirmed PiD for MAPT mutations and
found a novel mutation (c.1008G>C, p.Q336H) in 1 patient. Pathogenicity was
confirmed on microtubule assembly and tau filament formation assays. The patient
was compared with sporadic PiD and PiD associated with MAPT mutations from a
review of the literature. The patient had behavioral changes at 55 years of age,
followed by reduced verbal fluency, parkinsonism, and death at 63 years of age.
His mother and maternal uncle had similar symptoms. Recombinant tau with p.Q336H
mutation formed filaments faster than wild-type tau, especially with 3R tau. It
also promoted more microtubule assembly than wild-type tau. We conclude that
mutations in MAPT, including p.Q336H, can be associated with clinical,
pathologic, and biochemical features that are similar to those in sporadic PiD.
The pathomechanism of p.Q336H, and another previously reported variant at the
same codon (p.Q336R), seems to be unique to MAPT mutations in that they not only
predispose to abnormal tau filament formation but also facilitate microtubule
assembly in a 3R tau-dependent manner.
PMID- 26426268
TI - Neuronal ADAM10 Promotes Outgrowth of Small-Caliber Myelinated Axons in the
Peripheral Nervous System.
AB - The regulation of myelination and axonal outgrowth in the peripheral nervous
system is controlled by a complex signaling network involving various signaling
pathways. Members of the A Disintegrin And Metalloproteinase (ADAM) family are
membrane-anchored proteinases with both proteolytic and disintegrin
characteristics that modulate the function of signaling molecules. One family
member, ADAM17, is known to influence myelination by cleaving and thus regulating
one of the key signals, neuregulin-1, which controls peripheral nervous system
myelination. A similar function for ADAM10 had been suggested by previous in
vitro studies. Here, we assessed whether ADAM10 exerts a similar function in vivo
and deleted ADAM10 in a cell type-specific manner in either neurons or Schwann
cells. We found that ADAM10 is not required in either Schwann cells or neurons
for normal myelination during development or for remyelination after injury.
Instead, ADAM10 is required specifically in neurons for the outgrowth of
myelinated small-fiber axons in vitro and after injury in vivo. Thus, we report
for the first time a neuron-intrinsic function of ADAM10 in axonal regeneration
that is distinct from that of the related protein family member ADAM17 and that
may have implications for targeting ADAM function in nervous system diseases.
PMID- 26426267
TI - Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus
Infected Macaques Receiving Antiretroviral Therapy.
AB - Human immunodeficiency virus (HIV)-induced peripheral neuropathy is the most
common neurologic complication associated with HIV infection. In addition to
virus-mediated injury of the peripheral nervous system (PNS), treatment of HIV
infection with combination antiretroviral therapy (cART) may induce toxic
neuropathy as a side effect. Antiretroviral toxic neuropathy is clinically
indistinguishable from the sensory neuropathy induced by HIV; in some patients,
these 2 processes are likely superimposed. To study these intercurrent PNS
disease processes, we first established a simian immunodeficiency virus
(SIV)/pigtailed macaque model in which more than 90% of animals developed PNS
changes closely resembling those seen in HIV-infected individuals with distal
sensory neuropathy. To determine whether cART alters the progression of SIV
induced PNS damage, dorsal root ganglia and epidermal nerve fibers were evaluated
in SIV-infected macaques after long-term suppressive cART. Although cART
effectively suppressed SIV replication and reduced macrophage activation in the
dorsal root ganglia, PGP 9.5 immunostaining and measurements of epidermal nerve
fibers in the plantar surface of the feet of treated SIV-infected macaques
clearly showed that cART did not normalize epidermal nerve fiber density. These
findings illustrate that significant PNS damage persists in SIV-infected macaques
on suppressive cART.
PMID- 26426269
TI - Investigation of a Simple Model for Within-Flock Transmission of Scrapie.
AB - Genetic control programs for scrapie in sheep build on solid knowledge of how
susceptibility to scrapie is modulated by the prion protein genotype at the level
of an individual sheep. In order to satisfactorily analyze the effectivity of
control programs at the population level, insight is needed at the flock level,
i.e., how the grouping of sheep in flocks affects the population-level
transmission risk. In particular, one would like to understand how this risk is
affected by between-flock differences in genotype frequency distribution. A first
step is to model the scrapie transmission risk within a flock as a function of
the flock genotype profile. Here we do so by estimating parameters for a model of
within-flock transmission using genotyping data on Dutch flocks affected by
scrapie. We show that the data are consistent with a relatively simple
transmission model assuming horizontal transmission and homogeneous mixing
between animals. The model expresses the basic reproduction number for within
flock scrapie as a weighted average of genotype-specific susceptibilities,
multiplied by a single overall transmission parameter. The value of the overall
transmission parameter may vary between flocks to account for random between
flock variation in non-genetic determinants such as management practice. Here we
provide an estimate of its mean value and variation for Dutch flocks.
PMID- 26426270
TI - The Effect of Deworming on Growth in One-Year-Old Children Living in a Soil
Transmitted Helminth-Endemic Area of Peru: A Randomized Controlled Trial.
AB - BACKGROUND: Appropriate health and nutrition interventions to prevent long-term
adverse effects in children are necessary before two years of age. One such
intervention may include population-based deworming, recommended as of 12 months
of age by the World Health Organization in soil-transmitted helminth (STH)
endemic areas; however, the benefit of deworming has been understudied in early
preschool-age children. METHODOLOGY/PRINCIPAL FINDINGS: A randomized, double
blind, placebo-controlled trial was conducted to determine the effect of
deworming (500 mg single-dose crushed mebendazole tablet) on growth in one-year
old children in Iquitos, Peru. Children were enrolled during their routine 12
month growth and development clinic visit and followed up at their 18 and 24
month visits. Children were randomly allocated to: Group 1: deworming at 12
months and placebo at 18 months; Group 2: placebo at 12 months and deworming at
18 months; Group 3: deworming at both 12 and 18 months; or Group 4: placebo at
both 12 and 18 months (i.e. control group). The primary outcome was weight gain
at the 24-month visit. An intention-to-treat approach was used. A total of 1760
children were enrolled between September 2011 and June 2012. Follow-up of 1563
children (88.8%) was completed by July 2013. STH infection was of low prevalence
and predominantly light intensity in the study population. All groups gained
between 1.93 and 2.05 kg on average over 12 months; the average difference in
weight gain (kg) compared to placebo was: 0.05 (95% CI: -0.05, 0.17) in Group 1;
0.07 (95%CI: -0.17, 0.04) in Group 2; and 0.04 (95%CI: -0.06, 0.14) in Group 3.
There was no statistically significant difference in weight gain in any of the
deworming intervention groups compared to the control group. CONCLUSIONS:
Overall, with one year of follow-up, no effect of deworming on growth could be
detected in this population of preschool-age children. Low baseline STH
prevalence and intensity and/or access to deworming drugs outside of the trial
may have diluted the potential effect of the intervention. Additional research is
required to overcome these challenges and to contribute to strengthening the
evidence base on deworming. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01314937).
PMID- 26426271
TI - Incidence of HIV and Syphilis among Men Who Have Sex with Men (MSM) in Beijing:
An Open Cohort Study.
AB - BACKGROUND: This study investigated HIV and syphilis incidence among men who have
sex with men (MSM) in Beijing, China. METHODS: An open cohort was established
from September 2009 to April 2012. Participants were followed up with every three
to four months after recruitment and for thirty-one months in total. Chi-square
tests were used to compare demographic and behavioral characteristics between
participants who were followed up with and those lost to follow up. Univariate
and multivariate Cox proportional hazards regression analyses were used to
examine demographic and behavioral associations with HIV and syphilis incidence.
RESULTS: 69.7% (699/1,003) of the participants finished at least two follow-up
surveys during the study period. Variables which corresponded to increased loss
to follow-up included younger age, less education, non-identification of
homosexual identity, and migrant status. A total of 1,045 person-years (PYs) and
1,016.4 PYs were followed up for HIV and syphilis incidence estimation,
respectively. The HIV incidence was 5.9 per 100 PYs and 7.8 per 100 PYs for
syphilis. The predictors for the high HIV incidence included unsafe anal sex, sex
after drinking alcohol and STI infection. CONCLUSION: HIV incidence increased
rapidly within the cohort, but syphilis incidence remained stable and decreased.
More research is needed to provide multi-pronged HIV prevention interventions
among MSM in order to reduce the increasing burden of HIV and sexually
transmitted infections (STIs) in China.
PMID- 26426273
TI - Incidence and characterisation of spontaneous coronary artery dissection as a
cause of acute coronary syndrome--A single-centre Australian experience.
PMID- 26426272
TI - The White-Nose Syndrome Transcriptome: Activation of Anti-fungal Host Responses
in Wing Tissue of Hibernating Little Brown Myotis.
AB - White-nose syndrome (WNS) in North American bats is caused by an invasive
cutaneous infection by the psychrophilic fungus Pseudogymnoascus destructans
(Pd). We compared transcriptome-wide changes in gene expression using RNA-Seq on
wing skin tissue from hibernating little brown myotis (Myotis lucifugus) with WNS
to bats without Pd exposure. We found that WNS caused significant changes in gene
expression in hibernating bats including pathways involved in inflammation, wound
healing, and metabolism. Local acute inflammatory responses were initiated by
fungal invasion. Gene expression was increased for inflammatory cytokines,
including interleukins (IL) IL-1beta, IL-6, IL-17C, IL-20, IL-23A, IL-24, and G
CSF and chemokines, such as Ccl2 and Ccl20. This pattern of gene expression
changes demonstrates that WNS is accompanied by an innate anti-fungal host
response similar to that caused by cutaneous Candida albicans infections.
However, despite the apparent production of appropriate chemokines, immune cells
such as neutrophils and T cells do not appear to be recruited. We observed
upregulation of acute inflammatory genes, including prostaglandin G/H synthase 2
(cyclooxygenase-2), that generate eicosanoids and other nociception mediators. We
also observed differences in Pd gene expression that suggest host-pathogen
interactions that might determine WNS progression. We identified several classes
of potential virulence factors that are expressed in Pd during WNS, including
secreted proteases that may mediate tissue invasion. These results demonstrate
that hibernation does not prevent a local inflammatory response to Pd infection
but that recruitment of leukocytes to the site of infection does not occur. The
putative virulence factors may provide novel targets for treatment or prevention
of WNS. These observations support a dual role for inflammation during WNS;
inflammatory responses provide protection but excessive inflammation may
contribute to mortality, either by affecting torpor behavior or causing damage
upon emergence in the spring.
PMID- 26426274
TI - Importance of chronotropic response and left ventricular long-axis function for
exercise performance in patients with heart failure and preserved ejection
fraction.
AB - BACKGROUND: We evaluated the relationship between the degree of chronotropic
incompetence and left ventricular (LV) impairment during exercise with severity
of exercise intolerance in patients with heart failure and preserved ejection
fraction (HFPEF). METHODS: All patients underwent exercise echocardiography
during bicycle Ergometer exercise with the acquisition of long-axis tissue
Doppler imaging (TDI). Peak heart rates during exercise were also recorded and
the percentages of maximal age-predicted heart rate (%MPHR) and heart rate
reserve (%HRR) were calculated thereby. Besides, cardiopulmonary exercise testing
was performed with peak oxygen consumption (VO2) measuring averaged at the
highest 30-second during exercise. RESULTS: Forty HFPEF patients (aged 65+/-9
years; 75% male) were divided into two groups according to the median of peak
VO2: patients with peak VO2<16.5 and >=16.5 ml/kg/min, respectively. Patients
with lower peak VO2 had decreased peak heart rates, %MPHR, %HRR, stroke volume
and cardiac indices (LVSI and LVCI) than those with higher peak VO2 (all p<0.05).
The LV long-axis functions (TDI Sm, Em, s' and e') were reduced in patients with
lower peak VO2 (all p<0.05). Moreover, peak VO2 correlated with the following
parameters: peak heart rates, %MPHR, %HRR, LVSI, LVCI, TDI Sm, Em, s' and e'(all
p<0.05). CONCLUSIONS: The degree of blunted chronotropic response and impaired LV
long-axis function were more profound in HFPEF patients with poor exercise
performance.
PMID- 26426275
TI - Microvascular obstruction detected by cardiac MRI after AMI for the prediction of
LV remodeling and MACE: A meta-analysis of prospective trials.
PMID- 26426276
TI - Cardiac resynchronization therapy in chronic heart failure with moderately
reduced left ventricular ejection fraction: Lessons from the Multicenter InSync
Randomized Clinical Evaluation MIRACLE EF study.
AB - BACKGROUND: The benefits of CRT for symptomatic heart failure (HF) patients with
a wide QRS and reduced left ventricular ejection fraction (LVEF<=35%), are well
established .Post-hoc subgroup analyses suggest that CRT benefit may extend to
patients with LVEF>35%. METHODS: The MIRACLE EF was a prospective, randomized,
controlled, double-blinded study to evaluate CRT-P in NYHA II-III HF patients
with LBBB and with LVEF of 36%-50% and no previous pacing or ICD. The primary
endpoint was a composite of time to first HF event or death. All patients were
implanted with a CRT-P and randomized 2:1 to CRT-P ON or CRT-P OFF groups. The
minimum follow up time was 24 months. RESULTS: The MIRACLE EF study was stopped
for enrollment futility after 13 months and enrolling only 44 patients. The main
difficulties in recruiting patients were lack of eligible patients, previous ICD
implants, and the reluctance of institutions, patients or physicians to enroll in
the study which included a potential 5 year CRT OFF period. CONCLUSION: Despite a
careful design, identification and randomization of eligible patients were
challenging and a trial to assess morbidity and mortality trial was not feasible.
The MIRACLE EF experience illustrates the difficulties of designing a
scientifically robust but feasible study to assess potential new indications for
implantable devices. Smaller randomized studies with surrogate endpoints may
therefore be more reasonable, although the potential impact of such studies on
clinical practice, guidelines, and reimbursement remain to be determined.
PMID- 26426277
TI - Aerobic exercise improves cardiac autonomic modulation in women with polycystic
ovary syndrome.
AB - BACKGROUND: This study aimed to evaluate the effects of aerobic exercise on
cardiac autonomic modulation in women with polycystic ovary syndrome (PCOS).
METHODS: Thirty women with PCOS (25.8+/-4.8 years old; body mass index, BMI>=25
kg/m2) were divided into two groups; exercise group (n=15) and control group
(n=15). R-R interval was recorded during 15-min at rest in the supine position.
Heart rate variability (HRV) was analyzed by linear (rMSSD, SDNN, LF, HF, LFnu,
HFnu, and LF/HF) and nonlinear methods (Shannon entropy, SE; symbolic analyses, 0
V%, 1 V%, 2LV%, and 2UV%) at baseline and after 16 weeks. The multivariate
analysis of covariance was used to analyze the effects of exercise on HRV
indexes, adjusted for changes in BMI, fasting insulin, and testosterone level.
RESULTS: The exercise group increased parasympathetic modulation (rMSSD, HF,
HFnu, 2UV%; (p<0.05)) and decreased sympathetic modulation (LF, LFnu, 0 V%;
(p<0.05)) independently of changes in BMI, fasting insulin, and testosterone
level. Moreover, the exercise group decreased resting HR and systolic blood
pressure (p<0.05). All parameters remained unchanged in the control group.
CONCLUSIONS: Aerobic exercise increased vagal modulation and decreased
sympathetic modulation in women with PCOS. This finding reinforces the
recommendations for exercise during the clinical management of these patients.
PMID- 26426278
TI - The association of frailty with abnormal ankle-brachial index determinations is
related to age: Results from the Atahualpa Project.
PMID- 26426279
TI - Profile Changes in the Soil Microbial Community When Desert Becomes Oasis.
AB - The conversion of virgin desert into oasis farmland creates two contrasting types
of land-cover. During oasis formation with irrigation and fertilizer application,
however, the changes in the soil microbial population, which play critical roles
in the ecosystem, remain poorly understood. We applied high-throughput
pyrosequencing to investigate bacterial and archaeal communities throughout the
profile (0-3 m) in an experimental field, where irrigation and fertilization
began in 1990 and cropped with winter wheat since then. To assess the effects of
cultivation, the following treatments were compared with the virgin desert: CK
(no fertilizer), PK, NK, NP, NPK, NPKR, and NPKM (R: straw residue; M: manure
fertilizer). Irrigation had a greater impact on the overall microbial community
than fertilizer application. The greatest impact occurred in topsoil (0-0.2 m),
e.g., Cyanobacteria (25% total abundance) were most abundant in desert soil,
while Actinobacteria (26%) were most abundant in oasis soil. The proportions of
extremophilic and photosynthetic groups (e.g., Deinococcus-Thermus and
Cyanobacteria) decreased, while the proportions of R-strategy (e.g.,
Gammaproteobacteria including Xanthomonadales), nitrifying (e.g., Nitrospirae),
and anaerobic bacteria (e.g., Anaerolineae) increased throughout the oasis
profile. Archaea occurred only in oasis soil. The impact of fertilizer
application was mainly reflected in the non-dominant communities or finer
taxonomic divisions. Oasis formation led to a dramatic shift in microbial
community and enhanced soil enzyme activities. The rapidly increased soil
moisture and decreased salt caused by irrigation were responsible for this shift.
Furthermore, difference in fertilization and crop growth altered the organic
carbon contents in the soil, which resulted in differences of microbial
communities within oasis.
PMID- 26426281
TI - Clarifying the role of Ru in methanol oxidation at Ru(core)@Pt(shell)
nanoparticles.
AB - The catalytic activity of Rucore@Ptshell nanoparticles (NPs) towards CO
oxidation, a strongly adsorbed intermediate that compromises the performance of
direct methanol fuel cells, is known to be significantly better than at Pt alone.
However, a systematic study aimed at understanding the beneficial effect of Ru on
Pt during the methanol oxidation reaction (MOR) has not been carried out as yet.
Here, Rucore@Ptshell NPs, having a controlled Ptshell coverage of zero to two
monolayers and two different Rucore sizes (2 and 3 nm), were synthesized using
the simple polyol method to determine the precise role and impact of Ru on the
MOR in 0.5 M H2SO4 + 1 M methanol at RT and 60 degrees C. Because the structure
of our Rucore@Ptshell NPs is known with such certainty, we were able to show here
that the rate of methanol adsorption/dehydrogenation can be accelerated either by
compression of the Ptshell (by making the Rucore larger) when it is less than one
monolayer in thickness, or by decreasing the electronic effect of the Rucore on
the Ptshell (achieved by adding a second Pt layer to the Ptshell). At low
overpotentials, decreasing the Ptshell thickness also helps in increasing the
rate of the MOR by enhancing the rate of oxidation of adsorbed CO. Finally, it is
shown that the bi-functional effect of Ru on the Ptshell plays only a minor role
in the catalysis of the MOR, especially at large particles where CO surface
diffusion is facilitated.
PMID- 26426280
TI - The Combined Use of Correlative and Mechanistic Species Distribution Models
Benefits Low Conservation Status Species.
AB - Species can respond to climate change by tracking appropriate environmental
conditions in space, resulting in a range shift. Species Distribution Models
(SDMs) can help forecast such range shift responses. For few species, both
correlative and mechanistic SDMs were built, but allis shad (Alosa alosa), an
endangered anadromous fish species, is one of them. The main purpose of this
study was to provide a framework for joint analyses of correlative and
mechanistic SDMs projections in order to strengthen conservation measures for
species of conservation concern. Guidelines for joint representation and
subsequent interpretation of models outputs were defined and applied. The present
joint analysis was based on the novel mechanistic model GR3D (Global
Repositioning Dynamics of Diadromous fish Distribution) which was parameterized
on allis shad and then used to predict its future distribution along the European
Atlantic coast under different climate change scenarios (RCP 4.5 and RCP 8.5). We
then used a correlative SDM for this species to forecast its distribution across
the same geographic area and under the same climate change scenarios. First,
projections from correlative and mechanistic models provided congruent trends in
probability of habitat suitability and population dynamics. This agreement was
preferentially interpreted as referring to the species vulnerability to climate
change. Climate change could not be accordingly listed as a major threat for
allis shad. The congruence in predicted range limits between SDMs projections was
the next point of interest. The difference, when noticed, required to deepen our
understanding of the niche modelled by each approach. In this respect, the
relative position of the northern range limit between the two methods strongly
suggested here that a key biological process related to intraspecific variability
was potentially lacking in the mechanistic SDM. Based on our knowledge, we
hypothesized that local adaptations to cold temperatures deserved more attention
in terms of modelling, but further in conservation planning as well.
PMID- 26426282
TI - Palagonitization of Basalt Glass in the Flanks of Mid-Ocean Ridges: Implications
for the Bioenergetics of Oceanic Intracrustal Ecosystems.
AB - When basalt is exposed to oxygenated aqueous solutions, rims of palagonite form
along fractures at the expense of glass. We employed electron microprobe and
laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analyses
of fresh glass and adjacent palagonite crusts to determine the geochemical
changes involved in palagonite formation. Samples were retrieved from drill cores
taken in the North Pond Area, located on the western flank of the Mid-Atlantic
Ridge at 22 degrees 45'N and 46 degrees 05'W. We also analyzed whole rock powders
to determine the overall crust-seawater exchange in a young ridge flank.
Radioactive elements are enriched in palagonite relative to fresh glass, reaching
concentrations where radiolytic production of molecular hydrogen (H2) may be a
significant energy source. Based on these results, we hypothesize that microbial
ecosystems in ridge flank habitats undergo a transition in the principal energy
carrier, fueling carbon fixation from Fe oxidation in very young crust to H2
consumption in older crust. Unless the H2 is swept away by rapid fluid flow
(i.e., in young flanks), it may easily accumulate to levels high enough to
support chemolithoautotrophic life. In older flanks, crustal sealing and sediment
accumulation have slowed down seawater circulation, and the significance of
radiolytically produced H2 for catalytic energy supply is expected to increase
greatly. Similar habitats on other planetary surfaces are theoretically possible,
as accumulation of radiolytically produced hydrogen merely requires the presence
of H2O molecules and a porous medium, from which the hydrogen is not lost.
PMID- 26426283
TI - Emergence, institutionalization and renewal: Rhythms of adaptive governance in
complex social-ecological systems.
AB - Adaptive governance provides the capacity for environmental managers and decision
makers to confront variable degrees of uncertainty inherent to complex social
ecological systems. Current theoretical conceptualizations of adaptive governance
represent a series of structures and processes best suited for either adapting or
transforming existing environmental governance regimes towards forms flexible
enough to confront rapid ecological change. As the number of empirical examples
of adaptive governance described in the literature grows, the conceptual basis of
adaptive governance remains largely under theorized. We argue that reconnecting
adaptive governance with foundational concepts of ecological resilience
specifically Panarchy and the adaptive cycle of complex systems-highlights the
importance of episodic disturbances and cross-scale interactions in triggering
reorganizations in governance. By envisioning the processes of adaptive
governance through the lens of Panarchy, scholars and practitioners alike will be
better able to identify the emergence of adaptive governance, as well as take
advantage of opportunities to institutionalize this type of governance in pursuit
of sustainability outcomes. The synergistic analysis of adaptive governance and
Panarchy can provide critical insight for analyzing the role of social dynamics
during oscillating periods of stability and instability in social-ecological
systems. A deeper understanding of the potential for cross-scale interactions to
shape adaptive governance regimes may be useful as society faces the challenge of
mitigating the impacts of global environmental change.
PMID- 26426284
TI - Trends in the incidence of Oral and Pharyngeal Cancer (ICD00-14) in Guilan, North
of Iran.
AB - AIM: This study sought to assess the incidence of oral and pharyngeal cancer
based on ICD-10 in Guilan, Iran, from 2004 to 2009. METHOD: This retrospective
study assessed data collected from the Iranian cancer registries and
publications. The rate, age-standardized incidence, type, and location of lesions
according to ICD-10 were evaluated. Annual percent changes (APC) were estimated.
RESULTS: A total of 1533 head and neck cancers were recorded. Of them, 290 cases
(185 males and 105 females) were identified with oral and pharyngeal carcinoma
(ICD00-14) with a mean age of 58.92 +/- 17.94 years. The most common type of
cancer was oral squamous cell carcinoma (n = 156). Cancer of the oropharynx (ICD
06) and lips (ICD00) had high incidence. APC was 1.36%. ASR was 3.5 and 2.04 per
100 000 among males and females, respectively. The mean crude rate was 3.69 per 1
000 000. CONCLUSION: In contrast to the global cancer statistics (ICD 00-14),
Guilan showed lower incidence of oral and pharyngeal cancer during the understudy
years. Oral squamous cell carcinoma was the most common type of cancer in this
region.
PMID- 26426285
TI - Clinimetric properties and clinical utility in rehabilitation of postsurgical
scar rating scales: a systematic review.
AB - The aim of this study was to review and critically assess the most used and
clinimetrically sound outcome measures currently available for postsurgical scar
assessment in rehabilitation. We performed a systematic review of the Medline and
Embase databases to June 2015. All published peer-reviewed studies referring to
the development, validation, or clinical use of scales or questionnaires in
patients with linear scars were screened. Of 922 articles initially identified in
the literature search, 48 full-text articles were retrieved for assessment. Of
these, 16 fulfilled the inclusion criteria for data collection. Data were
collected pertaining to instrument item domains, validity, reliability, and Rasch
analysis. The eight outcome measures identified were as follows: Vancouver Scar
Scale, Dermatology Life Quality Index, Manchester Scar Scale, Patient and
Observer Scar Assessment Scale, Bock Quality of Life (Bock QoL) questionnaire,
Stony Brook Scar Evaluation Scale, Patient-Reported Impact of Scars Measure, and
Patient Scar Assessment Questionnaire. Scales were examined for their clinimetric
properties, and recommendations for their clinical or research use and selection
were made. There is currently no absolute gold standard to be used in
rehabilitation for the assessment of postsurgical scars, although the Patient and
Observer Scar Assessment Scale and the Patient-Reported Impact of Scars Measure
emerged as the most robust scales.
PMID- 26426290
TI - DNA barcodes from century-old type specimens using next-generation sequencing.
AB - Type specimens have high scientific importance because they provide the only
certain connection between the application of a Linnean name and a physical
specimen. Many other individuals may have been identified as a particular
species, but their linkage to the taxon concept is inferential. Because type
specimens are often more than a century old and have experienced conditions
unfavourable for DNA preservation, success in sequence recovery has been
uncertain. This study addresses this challenge by employing next-generation
sequencing (NGS) to recover sequences for the barcode region of the cytochrome c
oxidase 1 gene from small amounts of template DNA. DNA quality was first screened
in more than 1800 century-old type specimens of Lepidoptera by attempting to
recover 164-bp and 94-bp reads via Sanger sequencing. This analysis permitted the
assignment of each specimen to one of three DNA quality categories--high (164-bp
sequence), medium (94-bp sequence) or low (no sequence). Ten specimens from each
category were subsequently analysed via a PCR-based NGS protocol requiring very
little template DNA. It recovered sequence information from all specimens with
average read lengths ranging from 458 bp to 610 bp for the three DNA categories.
By sequencing ten specimens in each NGS run, costs were similar to Sanger
analysis. Future increases in the number of specimens processed in each run
promise substantial reductions in cost, making it possible to anticipate a future
where barcode sequences are available from most type specimens.
PMID- 26426291
TI - Comprehensive interactome of Otx2 in the adult mouse neural retina.
AB - The Otx2 homeodomain transcription factor exerts multiple functions in specific
developmental contexts, probably through the regulation of different sets of
genes. Protein partners of Otx2 have been shown to modulate its activity.
Therefore, the Otx2 interactome may play a key role in selecting a precise target
gene repertoire, hence determining its function in a specific tissue. To address
the nature of Otx2 interactome, we generated a new recombinant Otx2(CTAP-tag)
mouse line, designed for protein complexes purification. We validated this mouse
line by establishing the Otx2 interactome in the adult neural retina. In this
tissue, Otx2 is thought to have overlapping function with its paralog Crx. Our
analysis revealed that, in contrary to Crx, Otx2 did not develop interactions
with proteins that are known to regulate phototransduction genes but showed
specific partnership with factors associated with retinal development. The
relationship between Otx2 and Crx in the neural retina should therefore be
considered as complementarity rather than redundancy. Furthermore, study of the
Otx2 interactome revealed strong associations with RNA processing and translation
machineries, suggesting unexpected roles for Otx2 in the regulation of selected
target genes all along the transcription/translation pathway. The Otx2(CTAP-tag)
line, therefore, appears suitable for a systematic approach to Otx2 protein
protein interactions. genesis 53:685-694, 2015. (c) 2015 Wiley Periodicals, Inc.
PMID- 26426292
TI - Association of a (TTTA)n microsatellite and a TCT del/ins polymorphisms in the
aromatase gene (CYP19) with hip fracture risk in Mexican postmenopausal women.
AB - A (TTTA)n polymorphism in the aromatase gene has been studied in relation to bone
mineral density (BMD). The low number of TTTA repeats has been associated with
low BMD and fracture risk. The aim of this study was to search for associations
of TTTA copy number with hip fracture and lumbar spine osteoporosis in Mexican
peri and postmenopausal women. The allele with seven repeats was present in the
two reported versions, with or without a TCT deletion upstream of the
microsatellite (A1 and A2, respectively). After adjustment by confounders, the A1
allele and the A1A1 genotype were significantly associated with an elevated risk
of fracture (p = 0.034, OR = 3.2 [95% CI, 1.09-9.41] and p = 0.019, OR = 2.26
[95% CI, 1.14-4.49], respectively) and the A2 allele was associated with
protection of hip fracture (p = 0.04, OR = 0.48, [95% CI, 0.22-1.05]) as the A2A2
genotype (p = 0.048, OR = 0.29 [95% CI, 0.06-1.16]). The analysis allowed us to
defining the usefulness of the (TTTA)n polymorphism in the aromatase gene as an
indicator of hip fracture risk in Mexican population.
PMID- 26426293
TI - Mechanisms of fluorescence decays of colloidal CdSe-CdS/ZnS quantum dots
unraveled by time-resolved fluorescence measurement.
AB - By narrowing the detection bandpass and increasing the signal-to-noise ratio in
measuring the time-resolved fluorescence decay spectrum of colloidal CdSe-CdS/ZnS
quantum dots (QDs), we show that directly after the photoexcitation, the
fluorescence decay spectrum is characterized by a single exponential decay, which
represents the energy relaxation of the photogenerated exciton from its initial
high-energy state to the ground exciton state. The fluorescence decay spectrum of
long decay time is in the form of beta/t(2), where beta is the radiative
recombination time of the ground-state exciton and t is the decay time. Our
findings provide us with a direct and quantitative link between fluorescence
decay measurement data and fundamental photophysics of QD exciton, thereby
leading to a novel way of applying colloidal QDs to study microscopic, physical
and chemical processes in many fields including biomedicine.
PMID- 26426295
TI - Mechanical properties of ProTaper Gold nickel-titanium rotary instruments.
AB - AIM: To evaluate and compare the resistance to cyclic fatigue and torsional
stress, flexibility and surface microhardness of ProTaper Gold (PTG; Dentsply,
Tulsa Dental Specialties, Tulsa, OK, USA) system with ProTaper Universal (PTU;
Dentsply Maillefer, Ballaigues, Switzerland). METHODOLOGY: PTG and PTU
instruments were rotated in simulated canals and the number of cycles to failure
was recorded to assess their cyclic fatigue resistance. Torsional strength was
measured using a torsiometer after fixing firmly the apical 3 mm of the
instrument. A scanning electron microscope was used to characterize the
topographic features of the fracture surfaces of the broken instruments. The
instruments were tested for bending resistance using cantilever-bending test.
Vickers microhardness was measured on the cross section of instruments with 300 g
load and 15 s dwell time. Data were analysed statistically using independent t
tests. Statistical significance was set at P < 0.05. RESULTS: PTG instruments had
a significantly higher resistance to cyclic fatigue and flexibility than PTU (P <
0.001). The fractured cross-sectional surfaces revealed typical features of
cyclic fractures, including crack origins, fatigue zones and overload fast
fracture zones. On the other hand, PTU instruments were associated with higher
resistance to torsional stress and microhardness than PTG instruments (P <
0.001). After torsional tests, the fractured cross-sectional surfaces revealed
skewed dimples near the centre of the fracture surfaces and circular abrasion
streaks. CONCLUSIONS: The PTG instrument had improved resistance to cyclic
fatigue and flexibility compared with PTU. PTU instruments had improved
resistance to torsional stress and microhardness compared with PTG.
PMID- 26426294
TI - A kinetic model of municipal sludge degradation during non-catalytic wet
oxidation.
AB - Wet oxidation is a successful process for the treatment of municipal sludge. In
addition, the resulting effluent from wet oxidation is a useful carbon source for
subsequent biological nutrient removal processes in wastewater treatment. Owing
to limitations with current kinetic models, this study produced a kinetic model
which predicts the concentrations of key intermediate components during wet
oxidation. The model was regressed from lab-scale experiments and then
subsequently validated using data from a wet oxidation pilot plant. The model was
shown to be accurate in predicting the concentrations of each component, and
produced good results when applied to a plant 500 times larger in size. A
statistical study was undertaken to investigate the validity of the regressed
model parameters. Finally the usefulness of the model was demonstrated by
suggesting optimum operating conditions such that volatile fatty acids were
maximised.
PMID- 26426296
TI - A High-Throughput Genetic Complementation Assay in Yeast Cells Identified
Selective Inhibitors of Sphingosine Kinase 1 Not Found Using a Cell-Free Enzyme
Assay.
AB - Sphingosine kinase 1 (SphK1) is a lipid kinase that phosphorylates sphingosine to
produce the bioactive sphingolipid, sphingosine-1-phosphate (S1P), and therefore
represents a potential drug target for a variety of pathological processes such
as fibrosis, inflammation, and cancer. We developed two assays compatible with
high-throughput screening to identify small-molecule inhibitors of SphK1: a
purified component enzyme assay and a genetic complementation assay in yeast
cells. The biochemical enzyme assay measures the phosphorylation of sphingosine
fluorescein to S1P-fluorescein by recombinant human full-length SphK1 using an
immobilized metal affinity for phosphochemicals (IMAP) time-resolved fluorescence
resonance energy transfer format. The yeast assay employs an engineered strain of
Saccharomyces cerevisiae, in which the human gene encoding SphK1 replaced the
yeast ortholog and quantitates cell viability by measuring intracellular
adenosine 5'-triphosphate (ATP) using a luciferase-based luminescent readout. In
this assay, expression of human SphK1 was toxic, and the resulting yeast cell
death was prevented by SphK1 inhibitors. We optimized both assays in a 384-well
format and screened ~10(6) compounds selected from the Boehringer Ingelheim
library. The biochemical IMAP high-throughput screen identified 5,561
concentration-responsive hits, most of which were ATP competitive and not
selective over sphingosine kinase 2 (SphK2). The yeast screen identified 205
concentration-responsive hits, including several distinct compound series that
were selective against SphK2 and were not ATP competitive.
PMID- 26426298
TI - Risk of gentamicin toxicity in neonates treated for possible severe bacterial
infection in low- and middle-income countries: Systematic Review.
AB - OBJECTIVES: To assess the risk of gentamicin toxicity and potential number of
neonates exposed annually to this risk, through treatment with WHO-recommended
first-line antibiotics (gentamicin with penicillin) for the 6.9 million neonates
with possible serious bacterial infection (PSBI). METHODS: Systematic literature
review and assessment of the evidence using Cochrane and GRADE criteria. Meta
analysis was undertaken for pooled estimates where appropriate. RESULTS: Eleven
studies (946 neonates) were included (nine randomised controlled trials and two
prospective cohort studies). Six trials reported consistently measured
ototoxicity outcomes in neonates treated with gentamicin, and the pooled estimate
for hearing loss was 3% (95% CI 0-7%). Nephrotoxicity could not be assessed due
to variation in case definitions used. Estimates of the number of neonates
potentially affected by gentamicin toxicity were not undertaken due to
insufficient data. CONCLUSION: Given wider scale-up of outpatient-based and lower
level treatment of PSBI, improved data are essential to better assess the risks
from neonatal gentamicin treatment without assessment of blood levels, to
maximise benefit and reduce harm.
PMID- 26426299
TI - Hybrid percutaneous and surgical minimally invasive, thoracoscopy-guided removal
of a pacemaker lead subacutely perforating the right ventricle.
PMID- 26426300
TI - The predictive value of plasma biomarkers in discharged heart failure patients:
role of galectin-3.
AB - Over the last years a number of new biomarkers reflecting different aspects of
heart failure (HF) pathophysiology have been evaluated in order to improve
diagnosis and to better define prognosis of patients. Among these, Galectin 3
(Gal-3) seems particularly promising. It is a soluble beta galactoside-binding
lectin produced by activated macrophages which binds and activates the
fibroblasts thus leading to the deposition of collagen into the extracellular
matrix and to a progressive cardiac fibrosis. Gal-3 plays also an important
regulatory role in inflammatory status. Experimental studies have demonstrated
that it is involved in cardiac remodeling and that it is one of the main
determinants of development and progression of HF. In humans, Gal-3 plasma levels
are associated with the onset of HF in apparently healthy patients and have been
found being predictors of a worse prognosis in acute (AHF) as well as in chronic
heart failure (CHF). Furthermore, Gal-3 serum levels are strongly correlated with
renal dysfunction thus suggesting a possible role in better characterizing
cardiorenal syndrome. The aim of this review was to revise the available
experimental and clinical data concerning the role of Gal-3 as prognostic marker
in HF.
PMID- 26426301
TI - Identification and quantification of vinpocetine and picamilon in dietary
supplements sold in the United States.
AB - Vinpocetine and picamilon are drugs prescribed in many countries to treat a
variety of cerebrovascular disorders. In the United States, vinpocetine and
picamilon have never been approved by the US Food and Drug Administration, but
they are both available for sale directly to consumers as dietary supplements. We
designed our study to determine the accuracy of supplement labels with regard to
the presence and quantity of vinpocetine and picamilon. A validated ultra-high
performance liquid chromatography-photodiode-array method was developed for the
quantification of vinpocetine and picamilon. The separation was achieved using a
reversed phase (C-18) column, photodiode array detection, and water/acetonitrile
as the mobile phase. Vinpocetine and picamilon were detected at concentrations as
low as 10 and 50 ng/mL, respectively. The presence of vinpocetine and picamilon
was confirmed using reference standards. Twenty-three supplements labelled as
containing vinpocetine were available for sale at two large supplement retail
chains; 17 contained vinpocetine with quantities ranging from 0.3 to 32 mg per
recommended daily serving. No vinpocetine was detected in six of the sampled
supplements. The supplement label implied that vinpocetine was a constituent of
lesser periwinkle in three of the supplements. Of the 31 picamilon supplements
available for sale from a variety of retailers: 30 contained picamilon in
quantities ranging from 2.7 to 721.5 mg per recommended daily serving. We found
that consumers cannot obtain accurate information from supplement labels
regarding the presence or quantity of vinpocetine and picamilon. Copyright (c)
2015 John Wiley & Sons, Ltd.
PMID- 26426302
TI - Association between Macrophage Migration Inhibitory Factor Gene Variation and
Response to Glucocorticoid Treatment in Sudden Sensorineural Hearing Loss.
AB - Several lines of evidence suggest the role of the immune system in the
pathogenesis of sudden sensorineural hearing loss (SSNHL). Macrophage migration
inhibitory factor (MIF) mediates its role in various immune and inflammatory
conditions by the regulation of immune reactions. Several studies have confirmed
an association between MIF gene polymorphisms and susceptibility to various
inflammatory and autoimmune disorders. The aim of this study was to explore the
association between the MIF (-173 G/C) polymorphism (rs755622) and SSNHL in an
Iranian population. In this case-control association study, SSNHL cases (n = 77)
were included. Normal healthy subjects (n = 100) were also recruited from the
same region. Genotyping for MIF (-173 G/C) polymorphism was carried out using the
polymerase chain reaction-restriction fragment length polymorphism technique. The
frequency of the MIF -173 C allele carriers (GC + CC genotype) was significantly
elevated in SSNHL patients who responded to glucocorticoid treatment compared
with the patients with no response to treatment. These results suggest that the
MIF gene polymorphism is associated with a response to glucocorticoid treatment
in patients with SSNHL.
PMID- 26426303
TI - Highly Conductive Ionic-Liquid Gels Prepared with Orthogonal Double Networks of a
Low-Molecular-Weight Gelator and Cross-Linked Polymer.
AB - We prepared a heterogeneous double-network (DN) ionogel containing a low
molecular-weight gelator network and a polymer network that can exhibit high
ionic conductivity and high mechanical strength. An imidazolium-based ionic
liquid was first gelated by the molecular self-assembly of a low-molecular-weight
gelator (benzenetricarboxamide derivative), and methyl methacrylate was
polymerized with a cross-linker to form a cross-linked poly(methyl methacrylate)
(PMMA) network within the ionogel. Microscopic observation and calorimetric
measurement revealed that the fibrous network of the low-molecular-weight gelator
was maintained in the DN ionogel. The PMMA network strengthened the ionogel of
the low-molecular-weight gelator and allowed us to handle the ionogel using
tweezers. The orthogonal DNs produced ionogels with a broad range of storage
elastic moduli. DN ionogels with low PMMA concentrations exhibited high ionic
conductivity that was comparable to that of a neat ionic liquid. The present
study demonstrates that the ionic conductivities of the DN and single-network,
low-molecular-weight gelator or polymer ionogels strongly depended on their
storage elastic moduli.
PMID- 26426304
TI - Designing the shape evolution of SnSe2 nanosheets and their optoelectronic
properties.
AB - Layered chalcogenide materials (LCMs) are emerging materials in recent years for
their great potential in applications of electronics and optoelectronics. As a
member of LCMs, SnSe2, an n-type semiconductor with a band gap of ~1.0 eV, is of
great value to explore. In this paper, we develop a facile CVD method, for the
first time, to synthesize diverse shaped SnSe2 and square SnSe nanosheets (NSs)
on SiO2/Si substrates. To the best of our knowledge, the thickness of as-grown
SnSe2 is among the thinnest ones synthesized by CVD methods on various
substrates. What's more, photodetectors are fabricated to investigate the
optoelectronic properties of SnSe2. The on/off ratio of photoswitches reaches 100
under the illumination of an 800 nm laser. This work will pave a new pathway to
synthesize LCM nanostructures, shed light on the shape evolution during the
growth process and expand the candidates for high performance optoelectronic
devices.
PMID- 26426305
TI - Oncologic Outcomes according to the Treatment Strategy in Radiologic Complete
Responders after Neoadjuvant Chemoradiation for Rectal Cancer.
AB - OBJECTIVE: This study aimed to compare the oncologic outcomes between treatment
strategies for rectal cancer [radical surgery, local excision (LE), and the wait
and-see approach] in radiologic complete responders after neoadjuvant
chemoradiation (nCRT). METHODS: We retrospectively reviewed rectal cancer
patients and included 52 radiologic complete responders after nCRT defined as no
residual tumor or residual fibrosis and no suspicious metastatic lymph nodes on
magnetic resonance imaging (MRI). Clinicopathologic features and oncologic
outcomes were compared according to the treatment strategies. RESULTS: The median
follow-up period was 41 months (range, 6-80). Twenty-eight patients underwent
radical surgery, whereas 16 underwent LE, and 8 were closely monitored without
initial surgery. The pathologic complete response rate was 40.9%. Patients who
underwent radical surgery showed better prognosis compared to those who underwent
LE or wait-and-see (3-year disease-free survival: radical surgery 85.0% vs. LE
62.5%, wait-and-see 75.0%, p = 0.019; 3-year local recurrence-free survival:
radical surgery 96.4% vs. LE 67.0%, wait-and-see 75.0%, p = 0.009). After
recurrence, patients who underwent salvage surgery showed a relatively good
oncologic outcome. CONCLUSION: Pursuing LE or the wait-and-see approach instead
of radical surgery in rectal cancer patients undergoing nCRT may bring about a
detrimental oncologic outcome if clinical complete response is solely determined
by MRI.
PMID- 26426306
TI - Robust species taxonomy assignment algorithm for 16S rRNA NGS reads: application
to oral carcinoma samples.
AB - BACKGROUND: Usefulness of next-generation sequencing (NGS) in assessing bacteria
associated with oral squamous cell carcinoma (OSCC) has been undermined by
inability to classify reads to the species level. OBJECTIVE: The purpose of this
study was to develop a robust algorithm for species-level classification of NGS
reads from oral samples and to pilot test it for profiling bacteria within OSCC
tissues. METHODS: Bacterial 16S V1-V3 libraries were prepared from three OSCC DNA
samples and sequenced using 454's FLX chemistry. High-quality, well-aligned, and
non-chimeric reads >=350 bp were classified using a novel, multi-stage algorithm
that involves matching reads to reference sequences in revised versions of the
Human Oral Microbiome Database (HOMD), HOMD extended (HOMDEXT), and Greengene
Gold (GGG) at alignment coverage and percentage identity >=98%, followed by
assignment to species level based on top hit reference sequences. Priority was
given to hits in HOMD, then HOMDEXT and finally GGG. Unmatched reads were subject
to operational taxonomic unit analysis. RESULTS: Nearly, 92.8% of the reads were
matched to updated-HOMD 13.2, 1.83% to trusted-HOMDEXT, and 1.36% to modified
GGG. Of all matched reads, 99.6% were classified to species level. A total of 228
species-level taxa were identified, representing 11 phyla; the most abundant were
Proteobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Actinobacteria.
Thirty-five species-level taxa were detected in all samples. On average,
Prevotella oris, Neisseria flava, Neisseria flavescens/subflava, Fusobacterium
nucleatum ss polymorphum, Aggregatibacter segnis, Streptococcus mitis, and
Fusobacterium periodontium were the most abundant. Bacteroides fragilis, a
species rarely isolated from the oral cavity, was detected in two samples.
CONCLUSION: This multi-stage algorithm maximizes the fraction of reads classified
to the species level while ensuring reliable classification by giving priority to
the human, oral reference set. Applying the algorithm to OSCC samples revealed
high diversity. In addition to oral taxa, a number of human, non-oral taxa were
also identified, some of which are rarely detected in the oral cavity.
PMID- 26426307
TI - Mining Novel Allergens from Coconut Pollen Employing Manual De Novo Sequencing
and Homology-Driven Proteomics.
AB - Coconut pollen, one of the major palm pollen grains is an important constituent
among vectors of inhalant allergens in India and a major sensitizer for
respiratory allergy in susceptible patients. To gain insight into its allergenic
components, pollen proteins were analyzed by two-dimensional electrophoresis,
immunoblotted with coconut pollen sensitive patient sera, followed by mass
spectrometry of IgE reactive proteins. Coconut being largely unsequenced, a
proteomic workflow has been devised that combines the conventional database
dependent analysis of tandem mass spectral data and manual de novo sequencing
followed by a homology-based search for identifying the allergenic proteins. N
terminal acetylation helped to distinguish "b" ions from others, facilitating
reliable sequencing. This led to the identification of 12 allergenic proteins.
Cluster analysis with individual patient sera recognized vicilin-like protein as
a major allergen, which was purified to assess its in vitro allergenicity and
then partially sequenced. Other IgE-sensitive spots showed significant homology
with well-known allergenic proteins such as 11S globulin, enolase, and isoflavone
reductase along with a few which are reported as novel allergens. The allergens
identified can be used as potential candidates to develop hypoallergenic
vaccines, to design specific immunotherapy trials, and to enrich the repertoire
of existing IgE reactive proteins.
PMID- 26426308
TI - Spatial predictions at the community level: from current approaches to future
frameworks.
AB - A fundamental goal of ecological research is to understand and model how
processes generate patterns so that if conditions change, changes in the patterns
can be predicted. Different approaches have been proposed for modelling species
assemblage, but their use to predict spatial patterns of species richness and
other community attributes over a range of spatial and temporal scales remains
challenging. Different methods emphasize different processes of structuring
communities and different goals. In this review, we focus on models that were
developed for generating spatially explicit predictions of communities, with a
particular focus on species richness, composition, relative abundance and related
attributes. We first briefly describe the concepts and theories that span the
different drivers of species assembly. A combination of abiotic processes and
biotic mechanisms are thought to influence the community assembly process. In
this review, we describe four categories of drivers: (i) historical and
evolutionary, (ii) environmental, (iii) biotic, and (iv) stochastic. We discuss
the different modelling approaches proposed or applied at the community level and
examine them from different standpoints, i.e. the theoretical bases, the drivers
included, the source data, and the expected outputs, with special emphasis on
conservation needs under climate change. We also highlight the most promising
novelties, possible shortcomings, and potential extensions of existing methods.
Finally, we present new approaches to model and predict species assemblages by
reviewing promising 'integrative frameworks' and views that seek to incorporate
all drivers of community assembly into a unique modelling workflow. We discuss
the strengths and weaknesses of these new solutions and how they may hasten
progress in community-level modelling.
PMID- 26426309
TI - Digital microfluidics platform for interfacing solid-liquid extraction column
with portable capillary electropherograph for analysis of soil amino acids.
AB - In this work, the concept of a field-portable analyzer is proposed that operates
with milliliter amounts of solvents and samples. The need to develop such an
analyzer is not only driven by specific extraterrestrial analysis but also, for
example, by forensics applications where the amount of liquid that can be taken
to the field is severely limited. The prototype of the proposed analyzer consists
of a solid-liquid extractor, the output of which is connected to the micropump,
which delivers droplets of extracts to digital microfluidic platform (DMFP). In
this way, world-to-chip interfacing is established. Further, the sample droplets
are transported to CE capillary inlet port, separated and detected via a
contactless conductivity detector. Working buffers and other solvents needed to
perform CE analysis are also delivered as droplets to the DMFP and transported
through the CE capillary. The performance of the analyzer is demonstrated by
analysis of amino acids in sand matrices. The recovery of the spiked amino acids
from the inert sand sample was from 34 to 51% with analysis LOD from 0.2 to 0.6
ppm and migration time RSD from 0.2 to 6.0%.
PMID- 26426310
TI - Description and Phylogeny of Urostyla grandis wiackowskii subsp. nov.
(Ciliophora, Hypotricha) from an Estuarine Mangrove in Brazil.
AB - Interphase specimens, aspects of physiological reorganization and divisional
morphogenesis were investigated in a strain of a hypotrichous ciliate highly
similar to Urostyla grandis Ehrenberg, (type species of Urostyla), collected from
a mangrove area in the estuary of the Paraiba do Sul river (Rio de Janeiro,
Brazil). The results revealed that albeit interphase specimens match with the
known morphologic variability in U. grandis, morphogenetic processes have
conspicuous differences. Parental adoral zone is entirely renewed during
morphogenesis, and marginal cirri exhibit a unique combination of developmental
modes, in which left marginal rows originate from multiple anlagen arising from
innermost left marginal cirral row, whereas right marginal ciliature originates
from individual within-row anlagen. Based on such characteristics, a new
subspecies, namely U. grandis wiackowskii subsp. nov. is proposed, and
consequently, U. grandis grandis Ehrenberg, stat. nov. is established. Bayesian
and maximum-likelihood analyses of the 18S rDNA unambiguously placed U. grandis
wiackowskii as adelphotaxon of a cluster formed by other U. grandis sequences.
The implications of such findings to the systematics of Urostyla are discussed.
PMID- 26426311
TI - Expanding population edges: theories, traits, and trade-offs.
AB - Recent patterns of global change have highlighted the importance of understanding
the dynamics and mechanisms of species range shifts and expansions. Unique
demographic features, spatial processes, and selective pressures can result in
the accumulation and evolution of distinctive phenotypic traits at the leading
edges of expansions. We review the characteristics of expanding range margins and
highlight possible mechanisms for the appearance of phenotypic differences
between individuals at the leading edge and core of the range. The development of
life history traits that increase dispersal or reproductive ability is predicted
by theory and supported with extensive empirical evidence. Many examples of rapid
phenotypic change are associated with trade-offs that may influence the
persistence of the trait once expansion ends. Accounting for the effects of edge
phenotypes and related trade-offs could be critical for predicting the spread of
invasive species and population responses to climate change.
PMID- 26426313
TI - Electrochemistry of Nanostructured Layered Transition-Metal Dichalcogenides.
PMID- 26426312
TI - The Relationship Between Submental Surface Electromyography and Hyo-Laryngeal
Kinematic Measures of Mendelsohn Maneuver Duration.
AB - PURPOSE: The Mendelsohn Maneuver (MM) is a commonly prescribed technique that is
taught to individuals with dysphagia to improve swallowing ability. Due to cost
and safety concerns associated with videofluoroscopy (VFS) use, submental surface
electromyography (ssEMG) is commonly used in place of VFS to train the MM in
clinical and research settings. However, it is unknown whether ssEMG accurately
reflects the prolonged hyo-laryngeal movements required for execution of the MM.
The primary goal of this study was to examine the relationship among ssEMG
duration, duration of laryngeal vestibule closure, and duration of maximum hyoid
elevation during MM performance. METHOD: Participants included healthy adults and
patients with dysphagia due to stroke. All performed the MM during synchronous
ssEMG and VFS recording. RESULTS: Significant correlations between ssEMG duration
and VFS measures of hyo-laryngeal kinematic durations during MM performance
ranged from very weak to moderate. None of the correlations in the group of
stroke patients reached statistical significance. CONCLUSION: Clinicians and
researchers should consider that the MM involves novel hyo-laryngeal kinematics
that may be only moderately represented with ssEMG. Thus, there is a risk that
these target therapeutic movements are not consistently being trained.
PMID- 26426315
TI - Gastric emptying and disease activity in inflammatory bowel disease.
AB - BACKGROUND: Gastric emptying (GE) is delayed in a subset of patients with
inflammatory bowel disease (IBD). We have shown before that altered release of
gastrointestinal hormones may contribute to GE disturbances, but overall effects
of disease activity remain unclear. Thus, we aimed to evaluate GE in patients
with IBD during active disease and following therapy. DESIGN: A total of 20
healthy subjects (HC) and 26 patients with IBD hospitalized because of an acute
episode of their disease (Crohn's disease (CD) n = 13, ulcerative colitis (UC) n
= 13) underwent a standardized (13) C-octanoic acid GE breath test (baseline
test). Plasma glucose, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like
peptide-1 (GLP-1) were measured periodically throughout the test. A total of 16
patients underwent a second GE test after 3-4 months of therapy. RESULTS: At
baseline, nine patients with IBD had pathologically delayed GE half-time (T1/2 >
150 min) (P = 0.028 vs. HC). Moreover, T1/2 was significantly longer in the total
group of patients with IBD than in HC (129 +/- 12 min vs. 96 +/- 7, P = 0.030).
Postprandial GLP-1 responses were elevated in IBD (P = 0.002 vs. HC) and
correlated with T1/2 (P = 0.05). Following therapy clinical activity indices and
T1/2 were decreased in IBD (P <= 0.01 vs. baseline), and T1/2 no longer differed
from HC (P > 0.5). Moreover, GLP-1 plasma levels decreased significantly (P =
0.031). CONCLUSIONS: Higher disease activity in IBD is associated with prolonged
GE and increased release of GLP-1. Following effective therapy, GE is accelerated
and GLP-1 release decreases significantly. Thus, increased release of GLP-1 from
the inflamed mucosa might contribute to GE disturbances in IBD.
PMID- 26426316
TI - Pediatric deceased donor renal transplantation: An approach to decision making I.
Pediatric kidney allocation in the USA: The old and the new.
AB - Renal transplantation is the treatment of choice for children with end-stage
renal disease. More than 50% of children receive a deceased donor renal
transplant. Marked disparity between the number of children on the renal
transplant wait list and the supply has prompted numerous advances to increase
supply as well as maximize the utility of donor organs. Allocation of deceased
donor kidneys is based on several criteria. The organ allocation system policy is
continually evaluated and changed incrementally to optimize allocation. We, in
the United States, are in the process of transitioning into a new kidney
allocation system to enhance post-transplant survival benefit, increase
utilization of donated kidneys, and increase transplant access for biologically
disadvantaged candidates. This review will provide a brief overview of the organ
sharing system in the United States, compare the "old" and the "new" allocation
system, and discuss the considerations for the pediatric nephrologist while
accepting a deceased donor kidney for a particular pediatric patient.
PMID- 26426314
TI - Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report.
AB - BACKGROUND: Unexplained chronic cough (UCC) causes significant impairments in
quality of life. Effective assessment and treatment approaches are needed for
UCC. METHODS: This systematic review of randomized controlled trials (RCTs)
asked: What is the efficacy of treatment compared with usual care for cough
severity, cough frequency, and cough-related quality of life in patients with
UCC? Studies of adults and adolescents aged > 12 years with a chronic cough of >
8 weeks' duration that was unexplained after systematic investigation and
treatment were included and assessed for relevance and quality. Based on the
systematic review, guideline suggestions were developed and voted on by using the
American College of Chest Physicians organization methodology. RESULTS: Eleven
RCTs and five systematic reviews were included. The 11 RCTs reported data on 570
participants with chronic cough who received a variety of interventions. Study
quality was high in 10 RCTs. The studies used an assortment of descriptors and
assessments to identify UCC. Although gabapentin and morphine exhibited positive
effects on cough-related quality of life, only gabapentin was supported as a
treatment recommendation. Studies of inhaled corticosteroids (ICS) were affected
by intervention fidelity bias; when this factor was addressed, ICS were found to
be ineffective for UCC. Esomeprazole was ineffective for UCC without features of
gastroesophageal acid reflux. Studies addressing nonacid gastroesophageal reflux
disease were not identified. A multimodality speech pathology intervention
improved cough severity. CONCLUSIONS: The evidence supporting the diagnosis and
management of UCC is limited. UCC requires further study to establish agreed
terminology and the optimal methods of investigation using established criteria
for intervention fidelity. Speech pathology-based cough suppression is suggested
as a treatment option for UCC. This guideline presents suggestions for diagnosis
and treatment based on the best available evidence and identifies gaps in our
knowledge as well as areas for future research.
PMID- 26426317
TI - The Implementation and Evaluation of the Patient Admission Prediction Tool:
Assessing Its Impact on Decision-Making Strategies and Patient Flow Outcomes in 2
Australian Hospitals.
AB - STUDY OBJECTIVES: To evaluate the implementation of a Patient Admission
Prediction Tool (PAPT) in terms of patient flow outcomes and decision-making
strategies. METHODS: SETTING: The PAPT was implemented in 2 Australian public
teaching hospitals during October-December 2010 (hospital A) and October-December
2011 (hospital B). DESIGN: A multisite prospective, comparative (before and
after) design was used. Patient flow outcomes measured included access block and
hospital occupancy. Daily and weekly data were collected from patient flow
reports and routinely collected emergency department information by the site
champion and researchers. RESULTS: Daily decision-making strategies ranged from
business as usual to use of overcensus beds. Weekly strategies included advanced
approval to use of overcensus beds and prebooking nursing staff. These strategies
resulted in improved weekend discharges to manage incoming demand for the
following week. Following the introduction of the PAPT and workflow guidelines,
patient access and hospital occupancy levels could be maintained despite
increases in patient presentations (hospital A). CONCLUSIONS: The use of a PAPT,
embedded in patient flow management processes and championed by a manager, can
benefit bed and staff management. Further research that incorporates wider
evaluation of the use of the tool at other sites is warranted.
PMID- 26426318
TI - Increasing Efficiency in Evaluation of Chronic Cough: A Multidisciplinary,
Collaborative Approach.
AB - Chronic cough is the most common reason for medical office visits in the United
States. The typical patient has coughed more than 8 years and seen many
specialists. This quality improvement project is an ambulatory clinic redesign to
deliver efficient, patient-centered care with interspecialty collaboration.
Methodology included the Institute for Healthcare Improvement collaborative model
focused on Lean/Six Sigma and ADKAR (Awareness, Desire, Knowledge, Ability,
Reinforcement) Change Management. Interventions targeted education to referring
providers, implementation of software changes, building a collaborative
interdepartmental scheduling decision tree, and an interclinic dashboard
enhancing communication and decision support. Outcome measures compare group
resource utilization, evidenced by the total number of specialist referrals for
same indication of chronic cough (International Classification of Diseases, Ninth
Revision: 786.2), and length of time to complete evaluation. A retrospective
review of 165 medical records yielded 2 groups, "current care" (n = 67) and
"intervention" (n = 68). The number of specialist referrals per patient was
reduced in the intervention group (M = 1.22, SD = 0.48) compared with the current
care group (M = 3.33, SD = 1.02). Length of itinerary was reduced in the
intervention group (M = 11.90, SD = 12.13, GM = 6.82) compared with the current
care group (M = 126.93, SD = 158.13, GM = 54.8). Multidisciplinary collaboration,
communication, coordinating diagnosis, and management of multifactorial
conditions, such as chronic cough, are associated with lower costs and decreased
utilization of health care resources.
PMID- 26426319
TI - Patient Satisfaction in an Outpatient Hand Surgery Office: A Comparison of
English- and Spanish-Speaking Patients.
AB - BACKGROUND: As health care in the United States transitions from a fee-for
service to an outcomes-based environment, patient satisfaction is increasingly
incentivized and publicly reported. Despite the continued growth of the Latino
population and concomitant rise in the demand for health care, relatively little
is known regarding patient satisfaction in Spanish speakers. We sought to compare
patient satisfaction with hand surgery office visits between Spanish- and English
speaking patients. METHODS: Directly after the office visit, 150 patients (75
English speakers and 75 Spanish speakers) completed a sociodemographic survey, an
11-point ordinal rating of pain intensity, and a survey of satisfaction with the
encounter using items derived from the CG-CAHPS (Clinician and Group-Consumer
Assessment of Healthcare Providers and Systems) survey. Multivariable regression
modeling was used to identify factors associated with patient dissatisfaction.
RESULTS: Overall, 79% of Spanish-speaking patients were satisfied with the
physician as compared with 91% of English speakers (P = .041). Compared with
English-speaking patients, Spanish speakers were less likely to be satisfied with
provider listening carefully (91% vs 100%, P = .007) and spending enough time
with them (56% vs 93%, P < .001), as well as with waiting times (81% vs 96%, P =
.005). There was no difference with regard to provider showing respect, clarity
of communication, and explanation of what was done. Younger age and Spanish
language were independent predictors of patient dissatisfaction. CONCLUSIONS:
Spanish-speaking patients are less satisfied with the care provided in a hand
surgery office. In light of the growing diversity of the US population and the
fact that patient satisfaction is increasingly tied to reimbursement, additional
research might identify potential areas of improvement from both the surgeon (eg,
communication strategies, cultural competence) and patient (eg health literacy,
expectations) perspectives.
PMID- 26426320
TI - Electronic Tracking of Patients in an Outpatient Ophthalmology Clinic to Improve
Efficient Flow: A Feasibility Analysis and Benchmarking Study.
AB - INTRODUCTION: Real-time location systems (RTLS) and Lean management approaches
have been employed to improve patient flow in clinical settings. This study
explored the feasibility of using these methodologies in an outpatient resident
ophthalmology clinic. METHODS: Patients, providers, and staff in Wilmer Eye
Institute General Eye Services Clinic were provided RTLS tags to track their
movement throughout the clinic after observational studies modeling flow were
conducted. Tracking data guided changes for clinic processes based on Lean
management approaches, including reorganization of the reception desk,
consolidation of forms, creation of task sheets to improve communication,
installation of door flags on examination rooms, and training the staff in
service excellence. Tracking was repeated after changes were implemented. A
patient satisfaction survey was also conducted prior to and after the changes.
RESULTS: After intervention, significant increases were measured in the average
time patients spent in the clinic (99.3 minutes vs 112.8 minutes). Significant
decreases were seen in the times patients spent with the optometrists (15.4
minutes vs 12.1 minutes), testing (24.7 minutes vs 23.0 minutes), and together
with both the attending and the resident (8.3 minutes vs 5.8 minutes). The
patient satisfaction survey indicated improvements in patients' perception of the
helpfulness/friendliness of the staff, the length of time patients perceived they
waited, and overall clinic experience. DISCUSSION: Both RTLS and Lean management
approaches may be feasible ways to track and improve patient flow and
satisfaction if certain limitations can be overcome. This is the first published
report describing these approaches applied to an academic ophthalmology clinic in
the United States.
PMID- 26426321
TI - Factors Associated With Reintubation in Patients With Chronic Obstructive
Pulmonary Disease.
AB - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD)
increase morbidity, mortality, and health care costs in COPD patients. Patients
who require mechanical ventilation and fail extubation often have longer hospital
stays and/or increased mortality. Determining predictors to identify patients who
might require reintubation could help respiratory care teams manage these
patients better. METHODS: We retrospectively reviewed data of COPD patients over
a 3-year period. Inclusion criteria were patients with acute exacerbations of
COPD, age more than 45 years, and patients on mechanical ventilation. Exclusion
criteria were ventilated via tracheostomy, unplanned extubation, and reintubation
for reasons other than respiratory failure. RESULTS: This study included 88
patients; 61 patients were successfully extubated, 11 patients were extubated and
required reintubation, and 16 patients were not extubated during their intensive
care unit stay. There were no differences in demographic or clinical
characteristics between the patients with successful extubation and failed
extubation. Patients with successful extubation were more likely to have a "good
cough" assessment and to not receive any sedatives or analgesics in the 24 hours
prior to extubation than patients who failed extubation (P < .05). Multiple
variable logistic regression demonstrated that reintubation was significantly
associated with sedatives/analgesics given prior to extubation (odds ratio = 8.6;
95% confidence interval, 1.23-60.8). Intensive care unit and hospital lengths of
stay, tracheostomy events, and mortality rates were higher in the reintubation
group (P < .001). CONCLUSION: Sedative and analgesic drug use prior to extubation
was associated with more frequent reintubation in patients with acute
exacerbations of COPD. This study suggests that the judicious withdrawal of
sedatives prior to extubation may reduce reintubations.
PMID- 26426322
TI - A Simulated Level Loading of Supply and Demand for Beds in a Tertiary Care
Children's Hospital Reduces Overall Bed Requirements.
AB - BACKGROUND: Anticipating throughput and allocating resources effectively in
children's hospitals have unique challenges relative to adult inpatient centers.
The seasonal and daily variation can be difficult to anticipate in terms of
impact and creating plans for adequate preparation. Discrete event simulation
methodology can be helpful in determining appropriate allocation of resources and
has been increasingly appropriated in health care from industry. METHODS: A
representative sample set was abstracted from the Cohen Children's Medical Center
census tracking system to describe the present state. A larger data set was used
to determine the appropriate level load. The total work performed each hour from
8 AM to 8 PM was evaluated against the level load plan of 11.5%. During the
initial hours of the working period when the total work was low, more discharges
were added. For each discharge added, an equal quantity of discharges was
subtracted from the later hours of the day to bring the total work below 11.5%
for each hour. Once the simulated state discharges were determined, a new
aggregate bed supply line was created. These values were then added to the
original visualization to show improvement. RESULTS: Our analysis suggests that a
large part of the discharge/transfer activity and bed demand activity occurs in
the pediatric intensive care unit in a roughly 4- to 5-hour window. Our
simulation analysis suggests that level loading of this resource-intensive
activity period has a potential to reduce bed occupancy, increase bed
availability in peak bed demand times, and improve efficiency and throughput
throughout the hospital. CONCLUSION: Discrete event simulation can be an
effective tool for pediatric inpatient centers to determine appropriate
allocation of resources to enhance patient safety and throughput without
significant, costly expansion of bed capacity.
PMID- 26426323
TI - Collaboratively Improving Diabetes Care in Sweden Using a National Quality
Register: Successes and Challenges-A Case Study.
AB - BACKGROUND: Since 1996, the Swedish National Diabetes Register (NDR) enabled
health care providers to monitor their clinical performance over time and compare
it with the national average. All health systems of Swedish county councils
report data. By 2014, the NDR included data from 360 000 patients. Comparisons
among county councils show significant variations in clinical outcomes and in
adherence to evidence-based national guidelines. The purpose of this study was to
evaluate whether and how a quality improvement collaborative could influence
clinical practice and outcomes. METHODS: Twenty-three diabetes teams from all
over Sweden, both primary care units and internal medicine departments, joined a
quality improvement collaborative. The project was inspired by the Breakthrough
Collaborative Model and lasted for 20 months. Evaluation data were collected from
the teams' final reports and the NDR throughout the study period. RESULTS AND
CONCLUSION: The teams reported improved patient outcomes significantly compared
with the national average for systolic blood pressure and low-density lipoprotein
levels. In contrast, glycated hemoglobin A1c levels deteriorated in the whole NDR
population. Five themes of changes in practice were tested and implemented.
Success factors included improved teamwork, with active use of register data, and
testing new ideas and learning from others.
PMID- 26426324
TI - How Visual Management for Continuous Improvement Might Guide and Affect Hospital
Staff: A Case Study.
AB - Visual management (VM) tools such as whiteboards, often employed in Lean thinking
applications, are intended to be helpful in improving work processes in different
industries including health care. It remains unclear, however, how VM is actually
applied in health care Lean interventions and how it might influence the clinical
staff. We therefore examined how Lean-inspired VM using whiteboards for
continuous improvement efforts related to the hospital staff's work and
collaboration. Within a case study design, we combined semistructured interviews,
nonparticipant observations, and photography on 2 cardiology wards. The fate of
VM differed between the 2 wards; in one, it was well received by the staff and
enhanced continuous improvement efforts, whereas in the other ward, it was not
perceived to fit in the work flow or to make enough sense in order to be
sustained. Visual management may enable the staff and managers to allow
communication across time and facilitate teamwork by enabling the inclusion of
team members who are not present simultaneously; however, its adoption and value
seem contingent on finding a good fit with the local context. A combination of
continuous improvement and VM may be helpful in keeping the staff engaged in the
change process in the long run.
PMID- 26426328
TI - Correlation between Serum Levels of 3,3',5'-Triiodothyronine and Thyroid Hormones
Measured by Liquid Chromatography-Tandem Mass Spectrometry and Immunoassay.
AB - OBJECTIVE: For measuring serum 3,3',5'-triiodothyronine (rT3) levels,
radioimmunoassay (RIA) has traditionally been used owing to the lack of other
reliable methods; however, it has recently become difficult to perform.
Meanwhile, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has recently
been attracting attention as a novel alternative method in clinical chemistry. To
the best of our knowledge, there are no studies to date comparing results of the
quantification of human serum rT3 between LC-MS/MS and RIA. We therefore examined
the feasibility of LC-MS/MS as a novel alternative method for measuring serum
rT3, thyroxine (T4), and 3,5,3'-triiodothyronine (T3) levels. METHODS: Assay
validation was performed by LC-MS/MS using quality control samples of rT3, T4,
and T3 at 4 various concentrations which were prepared from reference compounds.
Serum samples of 50 outpatients in our department were quantified both by LC
MS/MS and conventional immunoassay for rT3, T4, and T3. Correlation coefficients
between the 2 measurement methods were statistically analyzed respectively.
RESULTS: Matrix effects were not observed with our method. Intra-day and inter
day precisions were less than 10.8% and 9.6% for each analyte at each quality
control level, respectively. Intra-day and inter-day accuracies were between
96.2% and 110%, and between 98.3% and 108.6%, respectively. The lower limit of
quantification was 0.05 ng/mL. Strong correlations were observed between the 2
measurement methods (correlation coefficient, T4: 0.976, p < 0.001; T3: 0.912, p
< 0.001; rT3: 0.928, p < 0.001). CONCLUSIONS: Our LC-MS/MS system requires no
manual cleanup operation, and the process after application of a sample is fully
automated; furthermore, it was found to be highly sensitive, and superior in both
precision and accuracy. The correlation between the 2 methods over a wide range
of concentrations was strong. LC-MS/MS is therefore expected to become a useful
tool for clinical diagnosis and research.
PMID- 26426329
TI - Concurrent Relations between Face Scanning and Language: A Cross-Syndrome Infant
Study.
AB - Typically developing (TD) infants enhance their learning of spoken language by
observing speakers' mouth movements. Given the fact that word learning is
seriously delayed in most children with neurodevelopmental disorders, we
hypothesized that this delay partly results from differences in visual face
scanning, e.g., focusing attention away from the mouth. To test this hypothesis,
we used an eye tracker to measure visual attention in 95 infants and toddlers
with Down syndrome (DS), fragile X syndrome (FXS), and Williams syndrome (WS),
and compared their data to 25 chronological- and mental-age matched 16-month-old
TD controls. We presented participants with two talking faces (one on each side
of the screen) and a sound (/ga/). One face (the congruent face) mouthed the
syllable that the participants could hear (i.e., /ga/), while the other face (the
incongruent face) mouthed a different syllable (/ba/) from the one they could
hear. As expected, we found that TD children with a relatively large vocabulary
made more fixations to the mouth region of the incongruent face than elsewhere.
However, toddlers with FXS or WS who had a relatively large receptive vocabulary
made more fixations to the eyes (rather than the mouth) of the incongruent face.
In DS, by contrast, fixations to the speaker's overall face (rather than to her
eyes or mouth) predicted vocabulary size. These findings suggest that, at some
point in development, different processes or strategies relating to visual
attention are involved in language acquisition in DS, FXS, and WS. This knowledge
may help further explain why language is delayed in children with
neurodevelopmental disorders. It also raises the possibility that syndrome
specific interventions should include an early focus on efficient face-scanning
behaviour.
PMID- 26426330
TI - Re-Annotator: Annotation Pipeline for Microarray Probe Sequences.
AB - Microarray technologies are established approaches for high throughput gene
expression, methylation and genotyping analysis. An accurate mapping of the array
probes is essential to generate reliable biological findings. However,
manufacturers of the microarray platforms typically provide incomplete and
outdated annotation tables, which often rely on older genome and transcriptome
versions that differ substantially from up-to-date sequence databases. Here, we
present the Re-Annotator, a re-annotation pipeline for microarray probe
sequences. It is primarily designed for gene expression microarrays but can also
be adapted to other types of microarrays. The Re-Annotator uses a custom-built
mRNA reference database to identify the positions of gene expression array probe
sequences. We applied Re-Annotator to the Illumina Human-HT12 v4 microarray
platform and found that about one quarter (25%) of the probes differed from the
manufacturer's annotation. In further computational experiments on experimental
gene expression data, we compared Re-Annotator to another probe re-annotation
tool, ReMOAT, and found that Re-Annotator provided an improved re-annotation of
microarray probes. A thorough re-annotation of probe information is crucial to
any microarray analysis. The Re-Annotator pipeline is freely available at
http://sourceforge.net/projects/reannotator along with re-annotated files for
Illumina microarrays HumanHT-12 v3/v4 and MouseRef-8 v2.
PMID- 26426332
TI - Facilitators and barriers for electronic social support.
AB - BACKGROUND: Nonprofit cancer societies play an important role in providing social
support for patients with cancer through nonprofit electronic counselling
services (ECS) provided by counselling nurses (CNs) with experience in oncology
nursing. To date, there exist only few studies addressing the facilitators and
barriers for social support of patients with cancer as reported by CNs.
OBJECTIVE: To describe the facilitators and barriers for electronic social
support of patients with cancer received from the ECS in the nonprofit cancer
societies as reported by CNs. METHODS: Qualitative design with three group
interviews was conducted with 10 CNs in three nonprofit cancer societies in
southern and western parts of Finland. Interviews were recorded, transcribed
verbatim and content analysed inductively. FINDINGS: The facilitators were
promotion of the access to ECS, functioning structures of ECS, utilisation of the
strengths of an individual CN in ECS, promotion of the life management of
patients, patient-centeredness as a basis of ECS and reliability of ECS. The
barriers for electronic social support were the unmet paths between ECS and
patients, nonfunctioning structures of ECS, inadequacy of mutual communication
and lack of shared viewpoints between CNs and patients. CONCLUSIONS: Facilitators
and barriers for electronic social support of patients with cancer were related
to organisation, individuals and counselling process. The counselling work in ECS
as its best promotes the life management of patients with cancer but,
alternatively, can lead to conflicts in communication and therefore be a barrier
for electronic social support. IMPLICATIONS FOR PRACTICE: To make the nonprofit
ECS better known, the cooperation with hospitals is needed to enable social
support for patients. To improve communication between CNs and patients,
continuous communications skills training and functional working environments are
needed.
PMID- 26426331
TI - Thermoresponsive release of viable microfiltrated Circulating Tumor Cells (CTCs)
for precision medicine applications.
AB - Stimulus responsive release of Circulating Tumor Cells (CTCs), with high recovery
rates from their capture platform, is highly desirable for off-chip analyses.
Here, we present a temperature responsive polymer coating method to achieve both
release as well as culture of viable CTCs captured from patient blood samples.
PMID- 26426333
TI - Potential Value of Cellulose Synthesis Inhibitors Combined With PHMB in the
Treatment of Acanthamoeba Keratitis.
AB - PURPOSE: The aim of this study was to improve the cytopathic effect (CPE) of
antiamebic agents by combining with cellulose synthesis inhibitor as an
encystation inhibitor. METHODS: Cellulose synthesis inhibitors, 2,6
dichlorobenzonitrile (DCB) and isoxaben were used to block encystation of
Acanthamoeba during cultivation. Cultured human corneal epithelial (HCE) cells
and Acanthamoeba were treated with polyhexamethylene biguanide (PHMB) combined
with cellulose synthesis inhibitors to evaluate the CPE as an antiamebic agent.
RESULTS: 0.02% PHMB showed a 51.9% CPE on HCE cells within 30 minutes but
exhibited significant toxic effects on Acanthamoeba. At a level of 0.00125%, PHMB
had no significant CPEs on HCE cells, whereas 100 MUM DCB and 10 MUM isoxaben
significantly inhibited the formation of the inner cyst wall of Acanthamoeba
during encystation, and Acanthamoeba trophozoites failed to convert into mature
cysts. Although a low concentration (0.00125%) of PHMB was used, the novel
combinations with 100 MUM DCB or 10 MUM isoxaben had 23.4% or 18.7% additional
amebicidal effects on Acanthamoeba. However, 100 MUM DCB and 10 MUM isoxaben had
no CPEs on HCE cells. CONCLUSIONS: The combination of cellulose synthesis
inhibitors with low concentrations of PHMB reduced the CPE on HCE cells and
improved the amebicidal effect on Acanthamoeba by inhibition of encystation.
PMID- 26426334
TI - Depressive Symptoms in Patients With Dry Eye Disease: A Case-Control Study Using
the Beck Depression Inventory.
AB - PURPOSE: To measure depressive symptoms in patients with dry eye disease (DED)
and controls using the Beck Depression Inventory (BDI) and to determine the
association between depressive and DED symptoms. METHODS: Fifty-three patients
with DED and 41 controls were recruited to the study. DED symptoms were assessed
using the Symptom Burden Tool and Ocular Surface Disease Index tool. Depressive
symptoms were assessed using the BDI. Regression diagnostics were performed to
detect outliers. Linear statistical models and polynomial regression were used to
determine the relationship between depressive symptoms and DED symptoms. An
independent t test was performed to determine differences in BDI scores between
cases and controls. Scatter plots were generated and linear regression was used
to estimate the association between scores. Logistic regression was used for the
DED dichotomous outcome and depression status as exposure. RESULTS: Regression
models revealed that the association is linear more than quadratic or cubic.
After adjusting for age, sex, race, and psychiatric medication, the regression
coefficient between DED symptoms and depressive symptoms among DED cases was 1.22
(95% confidence interval, 0.27-2.18). DED symptom scores and depression scores
were statistically significantly different between DED cases and controls.
Adjusted logistic regression revealed an odds ratio of 2.79 (95% confidence
interval, 0.96-8.12). CONCLUSIONS: This study provides further evidence regarding
the association between DED and depression and their symptoms. Prospective
studies are needed to understand the mechanisms underlying the association
between symptoms of depression and symptoms of DED.
PMID- 26426335
TI - Global Consensus on Keratoconus Diagnosis.
PMID- 26426336
TI - Graphane versus graphene: a computational investigation of the interaction of
nucleobases, aminoacids, heterocycles, small molecules (CO2, H2O, NH3, CH4, H2),
metal ions and onium ions.
AB - Graphane has emerged as a two-dimensional hydrocarbon with interesting physical
properties and potential applications. Understanding the interaction of graphane
with various molecules and ions is crucial to appreciate its potential
applications. We investigated the interaction of nucleobases, aminoacids,
saturated and unsaturated heterocycles, small molecules, metal ions and onium
ions with graphane by using density functional theory calculations. The preferred
orientations of these molecules and ions on the graphane surface have been
analysed. The binding energies of graphane with these molecules have been
compared with the corresponding binding energies of graphene. Our results reveal
that graphane forms stable complexes with all the molecules and ions yet showing
lesser binding affinity when compared to graphene. As an exemption, the
preferential strong binding of H2O with graphane than graphene reveals the fact
that graphane is more hydrophilic than graphene. Charge transfer between graphane
and the molecules and ions have been found to be an important factor in
determining the binding strength of the complexes. The effect of the interaction
of these molecules and ions on the HOMO-LUMO energy gap of graphane has also been
investigated.
PMID- 26426337
TI - Genetic Testing for BRCA Mutations Today and Tomorrow-About the ABOUT Study.
PMID- 26426339
TI - Hemoglobin oxidation at functional amino acid residues during routine storage of
red blood cells.
AB - BACKGROUND: Routine storage of red blood cells (RBCs) results in the progressive
accumulation of storage lesions. While the clinical relevance of these lesions is
still a matter of debate, alterations to RBC morphology and biochemistry,
especially in terms of energy and redox homeostasis, are likely to affect RBC
physiology and functionality at a minimum. Identification of oxidative
modifications that accumulate on key RBC proteins will help bridge the gap
between storage induced alterations and post-transfusion RBC viability. STUDY
DESIGN AND METHODS: Five AS-3 units were analyzed during routine storage via one
dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis-nano-high
performance liquid chromatography coupled online with tandem mass spectrometry
and advanced database searches. RESULTS: We identified oxidative modifications to
functional residues of hemoglobin (Hb) beta chain, including proximal histidine,
cysteine beta 94 (counting initiator methionine in the sequence), and histidine
144. Semiquantitative analysis indicates that up to approximately 20% of total Hb
could be targeted by these oxidative modifications that are overlooked by
standard proteomics approaches using routine database search conditions.
Progressive accumulation of oxidized residues in stored RBCs and selective
accumulation in vesicles was observed, further substantiating the hypothesis that
vesiculation represents a self-protective mechanism in ageing RBCs. CONCLUSION:
Several of the oxidized residues identified play well-established roles in heme
iron coordination, 2,3-diphosphoglycerate binding, and nitric oxide homeostasis.
Further functional and structural studies are necessary to determine possible
associations between these modifications and impaired gas transport homeostasis
in RBCs from old units.
PMID- 26426338
TI - Rad and Rem are non-canonical G-proteins with respect to the regulatory role of
guanine nucleotide binding in Ca(V)1.2 channel regulation.
AB - Rad and Rem are Ras-like G-proteins linked to diverse cardiovascular functions
and pathophysiology. Understanding how Rad and Rem are regulated is important for
deepened insights into their pathophysiological roles. As in other Ras-like G
proteins, Rad and Rem contain a conserved guanine-nucleotide binding domain (G
domain). Canonically, G-domains are key control modules, functioning as
nucleotide-regulated switches of G-protein activity. Whether Rad and Rem G
domains conform to this canonical paradigm is ambiguous. Here, we used multiple
functional measurements in HEK293 cells and cardiomyocytes (Ca(V)1.2 currents,
Ca(2+) transients, Ca(V)beta binding) as biosensors to probe the role of the G
domain in regulation of Rad and Rem function. We utilized Rad(S105N) and
Rem(T94N), which are the cognate mutants to Ras(S17N), a dominant-negative
variant of Ras that displays decreased nucleotide binding affinity. In HEK293
cells, over-expression of either Rad(S105N) or Rem(T94N) strongly inhibited
reconstituted Ca(V)1.2 currents to the same extent as their wild-type (wt)
counterparts, contrasting with reports that Rad(S105N) is functionally inert in
HEK293 cells. Adenovirus-mediated expression of either wt Rad or Rad(S105N) in
cardiomyocytes dramatically blocked L-type calcium current (I(Ca,L)) and
inhibited Ca(2+)-induced Ca(2+) release, contradicting reports that Rad(S105N)
acts as a dominant negative in heart. By contrast, Rem(T94N) was significantly
less effective than wt Rem at inhibiting I(Ca,L) and Ca(2+) transients in
cardiomyocytes. FRET analyses in cardiomyocytes revealed that both Rad(S105N) and
Rem(T94N) had moderately reduced binding affinity for Ca(V)betas relative to
their wt counterparts. The results indicate Rad and Rem are non-canonical G
proteins with respect to the regulatory role of their G-domain in Ca(V)1.2
regulation.
PMID- 26426340
TI - Analysis of BRAF and NRAS Mutation Status in Advanced Melanoma Patients Treated
with Anti-CTLA-4 Antibodies: Association with Overall Survival?
AB - Ipilimumab and tremelimumab are human monoclonal antibodies (Abs) against
cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show
a statistically significant benefit in overall survival in advanced melanoma
patients. Currently, there is no proven association between the BRAFV600 mutation
and the disease control rate in response to ipilimumab. This analysis was carried
out to assess if BRAFV600 and NRAS mutation status affects the clinical outcome
of anti-CTLA-4-treated melanoma patients. This is a retrospective multi-center
analysis of 101 patients, with confirmed BRAF and NRAS mutation status, treated
with anti-CTLA-4 antibodies from December 2006 until August 2012. The median
overall survival, defined from the treatment start date with the anti-CTLA-4. Abs
treatment to death or till last follow up, of BRAFV600 or NRAS mutant patients (n
= 62) was 10.12 months (95% CI 6.78-13.2) compared to 8.26 months (95% CI 6.02
19.9) in BRAFV600/NRASwt subpopulation (n = 39) (p = 0.67). The median OS of NRAS
mutated patients (n = 24) was 12.1 months and although was prolonged compared to
the median OS of BRAF mutated patients (n = 38, mOS = 8.03 months) or
BRAFV600/NRASwt patients (n = 39, mOS = 8.26 months) the difference didn't reach
statistical significance (p = 0.56). 69 patients were able to complete 4 cycles
of anti-CTLA-4 treatment. Of the 24 patients treated with selected BRAF- or MEK
inhibitors, 16 patients received anti-CTLA 4 Abs following either a BRAF or MEK
inhibitor with only 8 of them being able to finish 4 cycles of treatment. Based
on our results, there is no difference in the median OS in patients treated with
anti-CTLA-4 Abs implying that the BRAF/NRAS mutation status alone is not
sufficient to predict the outcome of patients treated with anti-CTLA-4 Abs.
PMID- 26426341
TI - External Validation of Models for Prediction of Lymph Node Metastasis in
Urothelial Carcinoma of the Bladder.
AB - PURPOSE: To externally validate models to predict LN metastsis; Karakiewicz
nomogram, clinical nodal staging score (cNSS), and pathologic nodal staging score
(pNSS) using a different cohort. MATERIALS AND METHODS: Clinicopathologic data
from 500 patients who underwent radical cystectomy and pelvic lymphadenectomy
were analyzed. The overall predictive values of models were compared with the
criteria of overall performance, discrimination, calibration, and clinical
usefulness. RESULTS: Presence of pN+ stages was recorded in 117 patients (23.4%).
Agreement between clinical and pathologic stage was noted in 174 (34.8%). Based
on Nagelkerke's peudo-R2 and brier score, pNSS demonstrated best overall
performance. Area under the receiver operating characteristics curve, showed that
pNSS had the best discriminatory ability. In all models, calibration was on
average correct (calibration-in-the-large coefficient = zero). On decision curve
analysis, pNSS performed better than other models across a wide range of
threshold probabilities. CONCLUSIONS: When compared to pNSS, current
precystectomy models such as the Karakiewicz nomogram and cNSS cannot predict the
probability of LN metastases accurately. The findings suggest that the
application of pNSS to Asian patients is feasible.
PMID- 26426343
TI - Diversity and population structure of northern switchgrass as revealed through
exome capture sequencing.
AB - Panicum virgatum L. (switchgrass) is a polyploid, perennial grass species that is
native to North America, and is being developed as a future biofuel feedstock
crop. Switchgrass is present primarily in two ecotypes: a northern upland
ecotype, composed of tetraploid and octoploid accessions, and a southern lowland
ecotype, composed of primarily tetraploid accessions. We employed high-coverage
exome capture sequencing (~2.4 Tb) to genotype 537 individuals from 45 upland and
21 lowland populations. From these data, we identified ~27 million single
nucleotide polymorphisms (SNPs), of which 1 590 653 high-confidence SNPs were
used in downstream analyses of diversity within and between the populations. From
the 66 populations, we identified five primary population groups within the
upland and lowland ecotypes, a result that was further supported through genetic
distance analysis. We identified conserved, ecotype-restricted, non-synonymous
SNPs that are predicted to affect the protein function of CONSTANS (CO) and EARLY
HEADING DATE 1 (EHD1), key genes involved in flowering, which may contribute to
the phenotypic differences between the two ecotypes. We also identified, relative
to the near-reference Kanlow population, 17 228 genes present in more copies than
in the reference genome (up-CNVs), 112 630 genes present in fewer copies than in
the reference genome (down-CNVs) and 14 430 presence/absence variants (PAVs),
affecting a total of 9979 genes, including two upland-specific CNV clusters. In
total, 45 719 genes were affected by an SNP, CNV, or PAV across the panel,
providing a firm foundation to identify functional variation associated with
phenotypic traits of interest for biofuel feedstock production.
PMID- 26426342
TI - Predicting Risk of Motor Vehicle Collisions in Patients with Glaucoma: A
Longitudinal Study.
AB - PURPOSE: To evaluate the ability of longitudinal Useful Field of View (UFOV) and
simulated driving measurements to predict future occurrence of motor vehicle
collision (MVC) in drivers with glaucoma. DESIGN: Prospective observational
cohort study. PARTICIPANTS: 117 drivers with glaucoma followed for an average of
2.1 +/- 0.5 years. METHODS: All subjects had standard automated perimetry (SAP),
UFOV, driving simulator, and cognitive assessment obtained at baseline and every
6 months during follow-up. The driving simulator evaluated reaction times to high
and low contrast peripheral divided attention stimuli presented while negotiating
a winding country road, with central driving task performance assessed as "curve
coherence". Drivers with MVC during follow-up were identified from Department of
Motor Vehicle records. MAIN OUTCOME MEASURES: Survival models were used to
evaluate the ability of driving simulator and UFOV to predict MVC over time,
adjusting for potential confounding factors. RESULTS: Mean age at baseline was
64.5 +/- 12.6 years. 11 of 117 (9.4%) drivers had a MVC during follow-up. In the
multivariable models, low contrast reaction time was significantly predictive of
MVC, with a hazard ratio (HR) of 2.19 per 1 SD slower reaction time (95% CI, 1.30
to 3.69; P = 0.003). UFOV divided attention was also significantly predictive of
MVC with a HR of 1.98 per 1 SD worse (95% CI, 1.10 to 3.57; P = 0.022). Global
SAP visual field indices in the better or worse eye were not predictive of MVC.
The longitudinal model including driving simulator performance was a better
predictor of MVC compared to UFOV (R2 = 0.41 vs R2 = 0.18). CONCLUSIONS:
Longitudinal divided attention metrics on the UFOV test and during simulated
driving were significantly predictive of risk of MVC in glaucoma patients. These
findings may help improve the understanding of factors associated with driving
impairment related to glaucoma.
PMID- 26426344
TI - Integration of High-k Oxide on MoS2 by Using Ozone Pretreatment for High
Performance MoS2 Top-Gated Transistor with Thickness-Dependent Carrier Scattering
Investigation.
AB - A top-gated MoS2 transistor with 6 nm thick HfO2 is fabricated using an ozone
pretreatment. The influence to the top-gated mobility brought about by the
deposition of HfO2 is studied statistically, for the first time. The top-gated
mobility is suppressed by the deposition of HfO2 , and multilayered samples are
less susceptible than monolayer ones.
PMID- 26426345
TI - Exciton-phonon scattering and nonradiative relaxation of excited carriers in
hydrothermally synthesized CdTe quantum dots.
AB - Naturally formed CdTe/CdS core/shell quantum dot (QD) structures in the presence
of surface stabilizing agents have been synthesized by a hydrothermal method.
Size and temperature dependent photoluminescence (PL) spectra have been
investigated to understand the exciton-phonon interaction, and radiative and
nonradiative relaxation of carriers in these QDs. The PL of these aqueous CdTe
QDs (3.0-4.8 nm) has been studied in the temperature range 15-300 K. The strength
of the exciton-LO-phonon coupling, as reflected in the Huang-Rhys parameter 'S'
is found to increase from 1.13 to 1.51 with the QD size varying from 4.8 to 3.0
nm. The PL linewidth (FWHM) increases with increase in temperature and is found
to have a maximum in the case of QDs of 3.0 nm in size, where the exciton
acoustic phonon coupling coefficient is enhanced to 51 MUeV K(-1), compared to
the bulk value of 0.72 MUeV K(-1). To understand the nonradiative processes,
which affect the relaxation of carriers, the integrated PL intensity is observed
as a function of temperature. The integrated PL intensity remains constant until
50 K for relatively large QDs (3.9-4.8 nm) beyond which a thermally activated
process takes over. Below 150 K, a small activation energy, 45-19 meV, is found
to be responsible for the quenching of the PL. Above 150 K, the thermal escape
from the dot assisted by scattering with multiple longitudinal optical (LO)
phonons is the main mechanism for the fast quenching of the PL. Besides this high
temperature quenching, interestingly for relatively smaller size QDs (3.4-3.0
nm), the PL intensity enhances as the temperature increases up to 90-130 K, which
is attributed to the emission of carriers from interface/trap states having an
activation energy in the range of 6-13 meV.
PMID- 26426346
TI - Synthesis of Triborylalkenes from Terminal Alkynes by Iridium-Catalyzed Tandem C
H Borylation and Diboration.
AB - A two-step reaction to convert terminal alkynes into triborylalkenes is reported.
In the first step, the terminal alkyne and pinacolborane (HBpin) are converted
into an alkynylboronate, which is catalyzed by an iridium complex supported by a
SiNN pincer ligand. In the second step, treatment of the reaction mixture with CO
generates a new catalyst which mediates dehydrogenative diboration of
alkynylboronate with pinacolborane. The mechanism of the diboration remains
unclear but it does not proceed via intermediacy of hydroboration products or via
B2 pin2.
PMID- 26426347
TI - Resilience factors play an important role in the mental health of parents when
children survive acute lymphoblastic leukaemia.
AB - AIM: Childhood cancer is a tremendous stressor that requires parents to adapt to
new challenges, and research has mainly focused on psychopathology and rarely on
a resource-oriented perspective, such as resilience. This study assessed
resilience factors among parents of children surviving acute lymphoblastic
leukaemia and parents of healthy children. We also explored the association
between parental resilience and mental health. METHODS: The study compared 57
parents of 40 children from eight to 15 years of age in remission from acute
lymphoblastic leukaemia and 63 parents of 42 healthy children. The Resilience
Scale for Adults and the General Health Questionnaire were used to assess
parental resilience and mental health. RESULTS: Parents of children surviving
acute lymphoblastic leukaemia showed significantly lower levels of resilience
than parents of healthy children, but no significant difference was found for
mental health. Certain resilience factors were positively associated with mental
health, especially for mothers, such as family cohesion, good perception of self
and being able to plan their future. CONCLUSION: Resilience factors may help to
protect parents' mental health, especially mothers, when their child has survived
acute lymphoblastic leukaemia and should be considered in a clinical setting.
Further research on resilience factors for fathers is needed.
PMID- 26426353
TI - Self-management for people with poorly controlled epilepsy: Participants' views
of the UK Self-Management in epILEpsy (SMILE) program.
AB - BACKGROUND: Epilepsy is a long-term condition that requires self-management, but
currently, there is no well-evaluated epilepsy self-education or self-management
intervention in the United Kingdom (UK). AIM: The aim of this study was to
examine the views and experiences of the first participants of the Self
Management in epILEpsy UK (SMILE UK) program to assist the development of a full
trial. METHOD: In-depth semistructured interviews and group discussions were
conducted with 10 people with poorly controlled epilepsy to explore their views
and experiences of the self-management program. Interviews were audio-recorded,
transcribed, and analyzed thematically. RESULTS: All participants viewed the
program positively. Three themes emerged: i) peer support was experienced through
knowledge sharing, disclosure of experiences, and exchange of contact details;
ii) participants felt better equipped to enter discussions with doctors and other
health-care professionals about their condition; and iii) participants reported
an improvement in their personal life through increased confidence to live with
epilepsy and acceptance of their diagnosis. CONCLUSION: A brief group self
management intervention increased knowledge and confidence in managing epilepsy.
PMID- 26426352
TI - The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol
in relation to CYP2C19 and CYP3A5 genotypes.
AB - AIM: The primary objective of the present study was to evaluate the
pharmacokinetic and pharmacodynamic interactions between clopidogrel and
cilostazol in relation to the CYP2C19 and CYP3A5 genotypes. METHODS: In a
randomized, three-way crossover study, 27 healthy subjects were administered
clopidogrel (300 mg), cilostazol (100 mg) or clopidogrel + cilostazol orally.
Plasma concentrations of clopidogrel, cilostazol and their active metabolites
(clopidogrel thiol metabolite, 3,4-dehydrocilostazol and 4"-trans
hydroxycilostazol), and adenosine diphosphate-induced platelet aggregation were
measured for pharmacokinetic and pharmacodynamic assessment. RESULTS: The area
under the plasma concentration-time curve (AUC) of the active thiol metabolite of
clopidogrel was highest in the CYP2C19 extensive metabolizers (EM) and lowest in
the poor metabolizers (PM). Cilostazol decreased the thiol metabolite AUC by 29%
in the CYP3A5*1/*3 genotype [geometric mean ratio (GMR) 0.71; 90% confidence
interval (CI) 0.58, 0.86; P = 0.020] but not in the CYP3A5*3/*3 genotype (GMR
0.93; 90% CI 0.80, 1.10; P = 0.446). Known effects of the CYP2C19 and CYP3A5
genotypes on the exposure of cilostazol and its metabolites were observed but
there was no significant difference in the AUC of cilostazol and 3,4
dehydrocilostazol between cilostazol and clopidogrel + cilostazol. The inhibition
of platelet aggregation from 4 h to 24 h (IPA4-24 ) following the administration
of clopidogrel alone was highest in the CYP2C19 EM genotype and lowest in the
CYP2C19 PM genotype (59.05 +/- 18.95 vs. 36.74 +/- 13.26, P = 0.023). However,
the IPA of the CYP2C19 PM following co-administration of clopidogrel and
cilostazol was comparable with that of the CYP2C19 EM and intermediate
metabolizers (IM) only in CYP3A5*3/*3 subjects. CONCLUSIONS: The additive
antiplatelet effect of cilostazol plus clopidogrel is maximized in subjects with
both the CYP2C19 PM and CYP3A5*3/*3 genotypes because of a lack of change of
clopidogrel thiol metabolite exposure in CYP3A5*3/*3 as well as the highest
cilostazol IPA in CYP2C19 PM and CYP3A5*3/*3 subjects.
PMID- 26426354
TI - A TaqMan-Based Multiplex qPCR Assay and DNA Extraction Method for Phylotype IIB
Sequevars 1&2 (Select Agent) Strains of Ralstonia solanacearum.
AB - Ralstonia solanacearum race 3 biovar 2 strains belonging to phylotype IIB,
sequevars 1 and 2 (IIB-1&2) cause brown rot of potato in temperate climates, and
are quarantined pathogens in Canada and Europe. Since these strains are not
established in the U.S. and because of their potential risk to the potato
industry, the U.S. government has listed them as select agents. Cultivated
geraniums are also a host and have the potential to spread the pathogen through
trade, and its extracts strongly inhibits DNA-based detection methods. We
designed four primer and probe sets for an improved qPCR method that targets
stable regions of DNA. RsSA1 and RsSA2 recognize IIB-1&2 strains, RsII recognizes
the current phylotype II (the newly proposed R. solanacearum species) strains
(and a non-plant associated R. mannitolilytica), and Cox1 recognizes eight plant
species including major hosts of R. solanacearum such as potato, tomato and
cultivated geranium as an internal plant control. We multiplexed the RsSA2 with
the RsII and Cox1 sets to provide two layers of detection of a positive IIB-1&2
sample, and to validate plant extracts and qPCR reactions. The TaqMan-based
uniplex and multiplex qPCR assays correctly identified 34 IIB-1&2 and 52
phylotype II strains out of 90 R. solanacearum species complex strains.
Additionally, the multiplex qPCR assay was validated successfully using 169
artificially inoculated symptomatic and asymptomatic plant samples from multiple
plant hosts including geranium. Furthermore, we developed an extraction buffer
that allowed for a quick and easy DNA extraction from infected plants including
geranium for detection of R. solanacearum by qPCR. Our multiplex qPCR assay,
especially when coupled with the quick extraction buffer method, allows for
quick, easy and reliable detection and differentiation of the IIB-1&2 strains of
R. solanacearum.
PMID- 26426355
TI - Nanostructured Carbon Allotropes with Weyl-like Loops and Points.
AB - Carbon allotropes are subject of intense investigations for their superb
structural, electronic, and chemical properties, but not for topological band
properties because of the lack of strong spin-orbit coupling (SOC). Here, we show
that conjugated p-orbital interactions, common to most carbon allotropes, can in
principle produce a new type of topological band structure, forming the so-called
Weyl-like semimetal in the absence of SOC. Taking a structurally stable
interpenetrated graphene network (IGN) as example, we show, by first-principles
calculations and tight-binding modeling, that its Fermi surface is made of two
symmetry-protected Weyl-like loops with linear dispersion along perpendicular
directions. These loops are reduced to Weyl-like points upon breaking of the
inversion symmetry. Because of the topological properties of these band-structure
anomalies, remarkably, at a surface terminated by vacuum there emerges a flat
band in the loop case and two Fermi arcs in the point case. These topological
carbon materials may also find applications in the fields of catalysts.
PMID- 26426358
TI - Health Human Resources Guidelines: Minimum staffing standards for cystic fibrosis
health care teams.
PMID- 26426357
TI - Ruthenium catalysts for water oxidation involving tetradentate polypyridine-type
ligands.
AB - A series of Ru(II) complexes that behave as water oxidation catalysts were
prepared involving a tetradentate equatorial ligand and two 4-substituted
pyridines as the axial ligands. Two of these complexes were derived from 2,9-di
(pyrid-2'-yl)-1,10-phenanthroline (dpp) and examine the effect of incorporating
electron-donating amino and bulky t-butyl groups on catalytic activity. A third
complex replaced the two distal pyridines with N-methylimidazoles that are more
electron-donating than the pyridines of dpp and potentially stabilize higher
oxidation states of the metal. The tetradentate ligand 2-(pyrid-2'-yl)-6
(1'',10''-phenanthrol-2''-yl)pyridine (bpy-phen), possessing a bonding cavity
similar to dpp, was also prepared. The Ru(II) complex of this ligand does not
have two rotatable pyridines in the equatorial plane and thus shows different
flexibility from the [Ru(dpp)] complexes. All the complexes showed activity
towards water oxidation. Investigation of their catalytic behavior and
electrochemical properties suggests that they may follow the same catalytic
pathway as the prototype [Ru(dpp)pic2](2+) involving a seven-coordinated
[Ru(IV)(O)] intermediate. The influence of coordination geometry on catalytic
performance is analyzed and discussed.
PMID- 26426356
TI - Positron emission tomography quantification of serotonin transporter binding in
medication-free bipolar disorder.
AB - OBJECTIVES: Bipolar disorder (BD) is associated with abnormalities in the
serotonin transporter (5-HTT), but specific in vivo findings have been
discrepant. Using positron emission tomography (PET) and [(11)C]DASB, we compared
5-HTT binding between unmedicated depressed BD subjects and healthy volunteers
(HVs). EXPERIMENTAL DESIGN: 5-HTT binding in six brain regions was compared
between 17 depressed, unmedicated BD subjects and 31 HVs, using the outcome
measure of VT/fP (proportional to the total number of available transporters).
Alternative outcome measures were examined as well. 47% of BD were BP I; and 65%
reported a prior suicide attempt. PRINCIPAL OBSERVATIONS: 5-HTT binding (VT/fP )
did not differ between BD and HV groups considering six brain regions of interest
simultaneously (P = 0.24). In contrast, alternative outcome measures (BPF*, BPP*,
and BPND*) indicated lower binding in BD compared with HV across these six
regions of interest (BPF*: P = 0.047; BPP*: P = 0.032; BPND*: P = 0.031). 5-HTT
binding was unrelated to suicide attempt history, depression severity, bipolar
subtype, or history of past substance use disorder. CONCLUSIONS: Choice of
outcome measure strongly affects comparisons of serotonin transporter binding
using PET with [(11)C]DASB. We do not find evidence of abnormal 5-HTT binding in
bipolar depression using our primary outcome measure, VT /fP . However, we did
observe lower 5-HTT binding in BD with alternative outcome measures that are
frequently used with [(11)C]DASB. Relative merits and assumptions of different
outcome measures are discussed. Evaluation in larger samples and during different
mood states, including remission, is warranted.
PMID- 26426359
TI - An adverse reaction in a pediatric sleep laboratory.
PMID- 26426361
TI - From Dispersed Microspheres to Interconnected Nanospheres: Carbon-Sandwiched
Monolayered MoS2 as High-Performance Anode of Li-Ion Batteries.
AB - Hierarchical structured carbon@MoS2 (C@MoS2) microspheres and nanospheres
composed of carbon-sandwiched monolayered MoS2 building blocks are synthesized
through a facile one-pot polyvinylpyrrolidone (PVP) micelle-assisted hydrothermal
route. The dimension and carbon content of C@MoS2 spheres are effectively
controlled by singly adjusting the concentration of PVP, which plays the dual
functions of soft-template and carbon source. As the anode materials of Li-ion
batteries, C@MoS2 nanospheres present considerably higher capacity, better rate
behavior and cycling stability than C@MoS2 microspheres. The reasons are
attributed to the unique interconnected nanospherical morphology and the internal
hierarchical construction of C@MoS2 nanospheres with expanded MoS2/carbon
interlayer spacing.
PMID- 26426360
TI - Compensatory Effect between Aortic Stiffening and Remodelling during Ageing.
AB - The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy
behaviour depends on a subtle balance between mechanical and geometrical
properties. Several clinical studies demonstrated that such a balance
progressively breaks down during ageing, when the aorta stiffens and remodels by
increasing its diameter. These two degenerative processes however, have different
impacts on the arterial wave pattern. They both tend to compensate for each
other, thus reducing the detrimental effect they would have had if they had
arisen individually. This remarkable compensatory mechanism is investigated by a
validated multi-scale model, with the aim to elucidate how aortic stiffening and
remodelling quantitatively impact the complex interplay between forward and
reflected backward waves in the arterial network. We focus on the aorta and on
the pressure at the ventricular-aortic interface, which epidemiological studies
demonstrate to play a key role in cardiovascular diseases.
PMID- 26426362
TI - Toll-like receptors 2, 4, and 9 in primary, metastasized, and recurrent oral
tongue squamous cell carcinomas.
AB - BACKGROUND: Toll-like receptors (TLRs) are pattern-recognizing proteins involved
in innate immunity and they seem to regulate both cancer progression and
inhibition. In oral cancer, TLR activation has been linked to invasion. To define
the role of TLR-2, TLR-4, and TLR-9 in oral tongue squamous cell carcinoma
(OTSCC), we studied their expression in vivo in OTSCC tumor samples, as well as
in vitro in cell invasion model. METHODS: We used immunohistochemistry to compare
the expression of TLR-2, TLR-4, and TLR-9 in 21 primary Stage I-II OTSCCs, neck
metastases, and recurrent tumors. In addition, we used myoma organotypic invasion
assay to evaluate the effect of GIT27 (4,5-dihydro-3-phenyl-5
isoxasoleaceticacid) on the invasion of the HSC-3 OTSCC cell line. RESULTS: TLR
2, TLR-4, and TLR-9 were expressed in most tumors. Nuclear TLR-2 expression
occurred more often in primary tumors than in neck metastases or recurrent tumors
of the neck, whereas nuclear TLR-4 expression and cytoplasmic TLR-9 expression
were higher in primary tumors than in local recurrent tumors. GIT27 did not
affect the invasion of HSC-3 OTSCC cells, but a myoma organotypic invasion assay
revealed that the expression of TLR-2 and TLR-4 was stronger in deeper-invading
cells. CONCLUSIONS: TLR-2, TLR-4, and TLR-9 were expressed in primary tumors,
neck metastases as well as in recurrent tumors of OTSCC. Thus, these receptors
seem to play a role in both the development and progression of tongue carcinoma.
These TLRs may also contribute to the invasive potential of OTSCC.
PMID- 26426363
TI - Conditioned Medium From Mesenchymal Stem Cells Enhances Early Bone Regeneration
After Maxillary Sinus Floor Elevation in Rabbits.
AB - PURPOSE: Conditioned medium from stem cells contains growth factors and has a
promising prospect for use in regenerative medicine. In this study, the effects
of marrow-derived stem cell-conditioned medium (MSC-CM) on bone regeneration
after maxillary sinus floor elevation were examined in rabbits. MATERIALS AND
METHODS: Rabbit bone marrow-derived stem cells (rMSCs) were cultured with MSC-CM
for 48 hours, and their mobilization and proliferation were evaluated. Beta
tricalcium phosphate scaffolds were impregnated with MSC-CM and grafted in the
rabbit maxillary sinus cavities. At 2, 4, and 8 weeks after transplantation,
sections of the newly formed bone were evaluated histologically and by
immunohistochemical staining. RESULTS: MSC-CM increased the migration and
proliferation of rMSCs and the early bone regeneration in rabbit sinus. Cell
proliferation and vascularization were increased at 2 weeks after implantation of
grafts impregnated with MSC-CM compared to controls, indicating that MSC-CM is
effective at the early phase of bone regeneration. CONCLUSION: MSC-CM is a
promising novel therapeutic agent to promote bone regeneration after maxillary
sinus floor elevation.
PMID- 26426364
TI - Acute hemorrhagic complications are associated with lower coated-platelet levels
in non-lacunar brain infarction.
AB - BACKGROUND: Coated platelets are procoagulant platelets observed upon dual
agonist stimulation with collagen and thrombin. Coated-platelet levels are
elevated in patients with non-lacunar ischemic stroke and decreased in patients
with spontaneous intracerebral hemorrhage as compared with controls. OBJECTIVE:
To investigate whether acute hemorrhagic complications occurring during the
initial hospital admission for non-lacunar ischemic stroke are associated with
lower coated-platelet levels. PATIENTS/METHODS: Coated-platelet levels were
determined in 385 consecutive patients with non-lacunar stroke. Hemorrhagic
complications were defined as either intracranial hemorrhage or significant
extracranial bleeding (drop in hemoglobin of >= 2 g dL(-1) ). The rate of acute
hemorrhagic complication was compared among subjects categorized into tertiles of
coated-platelet levels using an exact Cochrane-Armitage trend test. Logistic
regression was used to estimate the adjusted odds of hemorrhagic complication
associated with coated-platelet levels. RESULTS: Hemorrhagic complications were
present in 15 (3.9%) cases. Of these, four had intracranial hemorrhage and 11 had
extracranial hemorrhage. The occurrence of hemorrhagic complications differed
among the coated-platelet tertiles: 10.2% for the first tertile (coated-platelet
levels < 35.5%), 1.5% for the second tertile and 0% for the third tertile (coated
platelet levels >= 47.5%, trend test). Logistic regression showed that the odds
of hemorrhagic complication in those with levels < 35.5% were 14.59 times the
odds for patients with levels >= 35.5% (95% CI: 3.24-65.7). CONCLUSIONS: Lower
levels of procoagulant platelets are associated with acute hemorrhagic
complications following non-lacunar ischemic stroke. These results suggest a role
for coated-platelets in risk/benefit assessment in the early stages of stroke.
PMID- 26426370
TI - Unusual bonding modes of perfluorobenzene in its polymeric (dimeric, trimeric and
tetrameric) forms: entirely negative fluorine interacting cooperatively with
entirely negative fluorine.
AB - The F(delta-)...F(delta-) intermolecular synthon was recently observed to be
useful for generating a two-dimensional layered supramolecular architecture on
the Ag(111) surface (Kawai, et al., ACS Nano, 2015). This was formed when the
entirely negative covalently bonded fluorine atoms in
phenyleneethynylene(bis(2,3,5,6-tetrafluoro-4-(2,3,4,5,6
pentafluorophenylethynyl)phenyl)-ethyne (BPEPE-F18)) were in close proximity to
the same atoms in another BPEPE-F18 molecule. With a view to provide rigorous
insights into the physical chemistry of such an intermolecular synthon, we have
selected perfluorobenzene (C6F6) as a model compound, and have performed
extensive DFT-M06-2X/6-311++G(d,p) investigations on a number of its
homomolecular dimers, trimers, and tetramers. Of the twelve (C6F6)2 dimers
investigated, a displaced-parallel arrangement with an uncorrected binding energy
(DeltaE) of -7.4 kcal mol(-1) was found to be the most stable, and an
incorporation of the basis set superposition error (BSSE) has significantly
reduced its DeltaE to -4.7 kcal mol(-1). Besides, the DeltaE for a minimum-energy
least stable conformation of the same dimer, which involves a single sigmahole(
)...sigmahole(-) type F(delta-)...F(delta-) intermolecular bonding interaction,
amounts to -0.62 and -0.24 kcal mol(-1) without and with BSSE, respectively. The
geometry of another conformation of the dimer, which accompanies a set of three
F(delta-)...F(delta-) intermolecular interactions somehow similarly to those
observed in the layered supramolecular structure formed by the BPEPE-F18
molecules, lies at a relative energy of 6.5 kcal mol(-1) above the most stable
conformation. Passing from the latter dimer to an analogous (C6F6)3 trimer, as
well as from the trimer to an analogous (C6F6)4 tetramer, the latter two clusters
comprising windmill-type F(delta-)...F(delta-) intermolecular topologies, we have
marked a preferential increase in the value of DeltaE from -0.94 (dimer) to -2.76
(trimer) to -4.49 kcal mol(-1) (tetramer), thereby suggesting the presence of
cooperative binding. An energy decomposition analysis has revealed that
dispersion and polarization are the principal driving forces that bring the C6F6
molecules together in complex configurations. While a reasonable agreement was
found between the charge density based topological results of the intermolecular
bonding interactions that emerged from the application of Quantum Theory of Atoms
in Molecules (QTAIM) and Reduced Density Gradient approaches to all the polymeric
compounds, the results of the latter method were found to be too vague especially
near the (3, +1) ring critical point regions. QTAIM's source function analysis
has suggested that the fully negatively charged fluorine atoms in C6F6 serve as
sinks for the F(delta-)...F(delta-) bond formation.
PMID- 26426371
TI - Erratum.
PMID- 26426372
TI - Exhaled breath analysis, a simple tool to study the pathophysiology of
obstructive sleep apnoea.
AB - Accelerated airway inflammation may play a crucial role in the pathophysiology of
obstructive sleep apnoea (OSA); however this phenomenon has been investigated
only in a limited number of studies. The analysis of exhaled breath represents a
promising, non-invasive tool to evaluate airway inflammation in this context. The
knowledge on exhaled biomarkers in OSA has been growing with an emerging number
of methodological studies which help to interpret exhaled breath data. This
article not only summarises the results of studies on exhaled breath condensate
(EBC) biomarkers, exhaled volatile compounds and exhaled monoxides in OSA, but
also aims to critically review methodological limitations and provide some
guideline for further research.
PMID- 26426374
TI - Nutritional status and dental fluorosis among schoolchildren in communities with
different drinking water fluoride concentrations in a central region in Mexico.
AB - Poor water quality and under nutrition are important factors affecting the health
of many communities in developing countries. The aims of this study were: i) to
describe the fluoride water concentration and the hydrogeological conditions in a
region of a state located in the central in Mexico ii) to measure the association
between undernutrition and dental fluorosis in children living in communities
with different drinking water fluoride concentrations in a state located in the
central region of Mexico. METHODS: Field work was performed in the region to
identify the prevailing groundwater flow characteristics and water wells were
sampled to analyze water fluoride concentration. Children were selected from
three communities that had different drinking water fluoride concentrations
(i.e., 0.56, 0.70 and 1.60 mg/l). Fluoridated salt was available in these
communities. The Thylstrup-Fejerskov Index (TFI) was used to assess dental
fluorosis. Categories four or higher of this index involve changes in the entire
tooth surface (ITF >= 4). The weight and height of the children were measured.
The assessment of undernutrition was based on the World Health Organization
criteria: children were classified as being at risk of low-height (Height-for-Age
Z score < - 1.0 SD) and having low-height (Height-for-Age Z score < - 2.0 SD) for
age and sex, the same cutoff points of the Z score were used to classify "risk of
low-weight" and" low-weight children". RESULTS: In the region the mineralization
of the water captured by the wells is the result of a reaction with volcanic
materials. The water fluoride concentration in the region ranged from 0.2 to 1.6
mg/l. A total of 734 schoolchildren participated in the study. The percentage of
children in fluorosis categories (ITF >= 4) was 15.9%, 21.1% of the children were
at risk of low height-for-age, and 8.0% had low height-for-age. The percentage of
children with fluorosis (ITF >= 4) was 6.3%, 9.1% and 31.9% (p ? 0.001) and low
high-for-age was 2.9%, 2.5% and 8.4% (p ? 0.001), for the communities with F
concentrations of 0.56 mg/l, 0.70 mg/l and 1.6 mg/l, respectively. The logistic
regression model showed an association between dental fluorosis (TFI >= 4) and
low height-for-age (OR 2.09, p = 0.022) after adjusting for sex, number of teeth
erupted, source of drinking water, use of fluoridated toothpaste and tap water
fluoride concentration in the community. CONCLUSION: Children with low height-for
age were more likely to have dental fluorosis in the TFI categories that affect
the entire tooth surface. The results suggest that subpopulations with chronic
undernutrition are more susceptible to dental fluorosis.
PMID- 26426373
TI - Identification and BAC construction of Han, the first characterized HCMV clinical
strain in China.
AB - Human cytomegalovirus (HCMV) is the leading infectious cause of birth defects,
and may lead to severe or lethal diseases in immunocompromised individuals.
Several HCMV strains have been identified and widely applied in research, but no
isolate from China has been characterized. In the present study, we isolated,
characterized and sequenced the first Chinese HCMV clinical strain Han, and
constructed the novel and functional HCMV infectious clone Han-BAC-2311. HCMV Han
was isolated from the urine sample of a Chinese infant with multiple
developmental disorders. It expresses HCMV specific proteins and contains a
representative HCMV genome with minor differences compared to other strains. By
homologous recombination using mini-F derived BAC vector pUS-F6, the infectious
clone Han-BAC-2311 was constructed containing representative viral genes across
the HCMV genome. The insertion site and orientation of BAC sequence were
confirmed by restriction enzyme digestion and Southern blotting. The
reconstituted recombinant virus HanBAC-2311 expresses typical viral proteins with
the same pattern as that of wild-type Han, and also displayed a similar growth
kinetics to wild-type Han. The identification of the first clinical HCMV strain
in China and the construction of its infectious clone will greatly facilitate the
pathogenesis studies and vaccine development in China.
PMID- 26426375
TI - MuSIC report III: tumour microcirculation patterns and development of metastasis
in long-term follow-up of melanocytic uveal tumours.
AB - PURPOSE: To statistically determine differences in microcirculation patterns
between nevi and uveal melanomas and the influence of these patterns on
metastatic potential in the long-term follow-up of 112 patients with melanocytic
uveal tumours. In vivo markers indicating malignancy and metastatic potential
have implications for treatment decision. METHODS: Primary diagnosis and work-up
included clinical examination, fundus photography, standardized A and B scan
echography as well as evaluation of tumour microcirculation patterns via confocal
fluorescein and indocyanine green angiography (ICGA). Patient data were collected
from the patient files, the tumour registry or personal contact. Statistical
analysis was performed with spss 22.0 using chi-square, Fisher's exact test and
Kaplan-Meier survival analysis. RESULTS: Forty-three uveal melanocytic lesions
remained untreated and were retrospectively classified as benign nevi, whereas 69
lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and
'arcs without branching' were found significantly more often in nevi (p = 0.001
and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were
significantly more frequent in melanomas (p = 0.022 and p = 0.029). The
microcirculation pattern 'parallel with cross-linking' proved significantly more
frequent in patients who developed metastases (p = 0.001). CONCLUSIONS: Certain
microcirculation patterns may guide us in differentiating uveal nevi from
malignant melanomas. A non-invasive prognostic marker can be of great value for
borderline lesions in which cytology is less likely taken. 'Parallel with cross
linking' did not only indicate malignancy, but it was also associated with later
tumour metastasis.
PMID- 26426376
TI - Recurrent proliferating trichilemmal cyst of the scalp.
AB - Pilar tumors, commonly called trichilemmal cysts, are usually benign in nature,
malignant transformation (so called proliferating pilar tumors or proliferating
trichilemmal cysts [PTCs]) with high recurrence rates, local invasion and
metastases have been described. A 64-year-old women presented to our hospital
with a recurrent ulcerated mass lesion of the scalp. Non-contrast-enhanced
computed tomography scan of the head was performed. The mass was managed by
complete excisional biopsy and the defect closure was achieved by using a full
thickness skin graft. Histopathological analysis revealed the characteristic
structures of PTC; in addition foci of squamous pearls, squamous cells with
pleomorphic nuclei suggestive of cellular atypia and increased typical mitotic
activity were also noticed. PTCs are related to high recurrency rates, local
invasion and possible metastases. Radical surgical treatment and precise
histological analysis are essential in order to achieve a fast and complete
healing. Cooperation of the clinician and the pathologist is essential for
accurate diagnosis, treatment and follow-up planning.
PMID- 26426377
TI - Inflammatory linear verrucous epidermal nevus: an unusual manifestation.
PMID- 26426378
TI - Performance of a Branch Chain RNA In Situ Hybridization Assay for the Detection
of High-risk Human Papillomavirus in Head and Neck Squamous Cell Carcinoma.
AB - High-risk human papillomavirus (HR-HPV) is a major etiologic agent in a subset of
head and neck squamous cell carcinomas (HNSCCs), and its recognition has
prognostic and predictive implications. The availability of a sensitive and
specific test to assess HR-HPV status is limited. We evaluate an RNA in situ
hybridization (ISH) method using branch chain technology to detect HR-HPV and
compare its results with DNA ISH, p16 immunohistochemistry, and polymerase chain
reaction (PCR). Tissue sections from 54 patients were stained with a manual RNA
ISH assay (ViewRNA), which detects 14 HR-HPV types, an automated DNA ISH assay,
and p16 immunohistochemistry. Most cases (83%, n=45) were also tested on an
automated platform for 14 HR-HPV types and 1 limited to HPV 16/18. PCR was
performed in all cases and was successful in 93% (n=50). The RNA ISH assay
produced results in 96% of the cases with strong signals and was easily
interpreted. HR-HPV was detected in more cases (63%, n=34) by RNA ISH than by DNA
ISH (39%, n=21). Compared with PCR, both ISH platforms were 94% specific. RNA ISH
was more sensitive (91%) than DNA ISH (65%), and RNA ISH correlated more strongly
with p16 immunostaining. HPV 16 represented 89% of HR-HPV detected. The cocktail
HPV 16/18 platform was concordant with the pooled HR-HPV assay in all expected
cases. The automated assay demonstrated high concordance (96%) with the manual
version, showed decreased background, and should allow for easy implementation
into the workflow of the diagnostic pathology laboratory.
PMID- 26426379
TI - Do Clear Cell Papillary Renal Cell Carcinomas Have Malignant Potential?
AB - There have been no recurrences or metastases of clear cell papillary renal cell
carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language
literature. We identified all our cases of CCPRCC (1990 to 2013), reviewing all
cases that preceded the formal designation of the entity. Immunohistochemical
stains were performed on 32 cases during their initial workup. In addition,
stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one
with atypical follow-up and the other with a more compact morphology, although
not performed initially. An extended panel with AMACR, CD10, and renal cell
carcinoma (RCC) was added to the case with atypical follow-up. Fluorescence in
situ hybridization for chromosomes 3p, 7, and 17 was performed on the latter case
and on another clinically presumed metastatic tumor. In classic cases,
immunohistochemical staining was not performed. Fifty-eight patients (31 women;
27 men) with follow-up data were included in our study; 39 cases were from our
consult service. The patients' ages ranged from 36 to 83 years. Thirty-five
patients had cystic or partially cystic lesions; 6 tumors were multifocal, 3 of
which were bilateral. The majority (53 patients; 91.4%) presented with stage pT1
disease (size range, 0.2 to 8 cm), 2 patients presented with pT2 disease (8.5 and
10.3 cm), 1 patient presented with pT3 disease (6.5 cm sarcomatoid RCC focally
extending out of the kidney), and pathologic stage was unavailable in 2 cases.
Treatment consisted of 29 partial nephrectomies, 26 radical nephrectomies, 2
cryoablations, and 1 cyst ablation. The resection margins were negative in all
but one case, with this case disease free after a 26-month period. Two patients
had intraoperative tumor disruption and were disease free at 9 and 34 months.
Five patients had synchronous ipsilateral renal cell carcinomas (non-CCPRCC).
Mean follow-up time was 21 months (range, 1 to 175 mo), with all but 3 patients
having no evidence of disease. One patient was presumed to have contralateral
disease on the basis of imaging findings and is alive and well 37 months after
multiple partial nephrectomies. Metastatic disease to the lung was clinically
presumed in 1 patient in whom a higher-grade lesion may have been missed during
sampling of the predominantly cystic pT1b tumor and tissue confirmation of the
metastases was not obtained. Another case presented with multiple skeletal and
pulmonary metastases 8 months after resection of pT3 sarcomatoid CCPRCC. The
patient with the sarcomatoid RCC died of multifocal skeletal and pulmonary
metastatic disease 13 months after resection of the renal tumor. Our study, the
largest to date with follow-up, along with others, suggests that pure CCPRCC is
an indolent tumor and should be renamed "clear cell papillary neoplasm of low
malignant potential" to reflect their biology.
PMID- 26426380
TI - Perineural Invasion is a Strong Prognostic Factor in Colorectal Cancer: A
Systematic Review.
AB - Perineural invasion (PNI) is a possible route for metastatic spread in various
cancer types, including colorectal cancer (CRC). PNI is linked to poor prognosis,
but systematic analyses are lacking. This study systematically reviews the
frequency and impact of PNI in CRC. A literature search was performed using
PubMed database from inception to January 1, 2014. Data were analyzed using
Review Manager 5.3. A quality assessment was performed on the basis of modified
REMARK criteria. Endpoints were local recurrence (LR), 5-year disease-free
survival (5yDFS), 5-year cancer-specific survival (5yCSS), and 5-year overall
survival (5yOS). Meta-analysis was performed in terms of risk ratios (RR) and
hazard ratios (HR) with 95% confidence interval (95% CI). In this meta-analysis,
58 articles with 22,900 patients were included. PNI was present in 18.2% of
tumors. PNI is correlated with increased LR (RR 3.22, 95% CI, 2.33-4.44) and
decreased 5yDFS (RR 2.35, 95% CI, 1.66-3.31), 5yCSS (RR 3.61, 95% CI, 2.76-4.72),
and 5yOS (RR 2.09, 95% CI, 1.68-2.61). In multivariate analysis PNI remains an
independent prognostic factor for 5yDFS, 5yCSS, and 5yOS (HR 2.35, 95% CI, 1.97
3.08; HR 1.91, 95% CI, 1.50-2.42; and HR 1.85, 95% CI, 1.63-2.12, respectively).
We confirmed the strong impact of PNI for LR and survival in CRC. The prognostic
value of PNI is similar to that of well-established prognostic factors as depth
of invasion, differentiation grade, lymph node metastases, and lymphatic and
extramural vascular invasion. Therefore, PNI should be one of the factors in the
standardized reporting of CRC and might be considered a high-risk feature.
PMID- 26426382
TI - Carcinoma of the Uterine Cervix Involving the Genitourinary Tract: A Potential
Diagnostic Dilemma.
AB - Uterine cervical carcinoma secondarily involving the genitourinary tract is
rarely documented histologically. These tumors present a unique diagnostic
challenge as they can appear morphologically similar to urothelial carcinoma as
well as primary squamous cell carcinoma and primary adenocarcinoma of the
bladder. Genitourinary consult cases at the Johns Hopkins Hospital from 1984 to
the present were searched for cases in which the differential diagnosis was
primary bladder carcinoma versus secondary involvement by cervical carcinoma. We
identified 10 cases that met these criteria and evaluated them by
immunohistochemistry for p16 and GATA3 and in situ hybridization for human
papillomavirus (HPV). Six cases were received with a gynecologic history. Four
cases had been misdiagnosed as urothelial carcinoma, and 1 case was favored to be
cystitis cystica et glandularis by the submitting institutions. Morphologically,
the majority of cases showed basaloid nests of tumor cells infiltrating muscle
bundles, with several having foci that mimicked urothelial carcinoma in situ. Six
tumors were found to be diffusely positive with p16, 1 tumor was patchy, 1 was
weak, and 2 were negative. GATA3 staining was negative in 6 cases, and 4 showed
weak to strong positivity. Eight cases were positive for high-risk HPV (6 were
positive for HPV 16, and 1 was positive for HPV 18). In the 2 cases that were
negative for HPV by in situ hybridization, characteristic morphologic features of
HPV-unrelated type of endocervical adenocarcinoma were present. On the basis of
our findings we advocate a multifaceted approach, combining morphologic
evaluation with ancillary studies including immunohistochemistry and in situ
hybridization in the evaluation of genitourinary specimens for secondary
involvement by cervical carcinoma. Furthermore, gynecologic clinical history is
absolutely critical and most important to the evaluation and diagnosis of these
specimens, as these ancillary studies are not completely sensitive or specific.
PMID- 26426381
TI - NOTCH1, TP53, and MAP2K1 Mutations in Splenic Diffuse Red Pulp Small B-cell
Lymphoma Are Associated With Progressive Disease.
AB - Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is considered an indolent
neoplasm and its pathogenesis is not well known. We investigated the molecular
characteristics of 19 SDRPL patients, 5 of them with progressive disease. IGHV
genes were mutated in 9/13 (69%). Cytogenetic and molecular studies identified
complex karyotypes in 2 cases, and IGH rearrangements in 3, with PAX5 and
potentially TCL1 as partners in each one of them. Copy number arrays showed
aberrations in 69% of the tumors, including recurrent losses of 10q23, 14q31-q32,
and 17p13 in 3, and 9p21 in 2 cases. Deletion of 7q31.3-q32.3 was present in only
1 case and no trisomies 3 or 18 were detected. NOTCH1 and MAP2K1 were mutated in
2 cases each, whereas BRAF, TP53, and SF3B1 were mutated each in single cases. No
mutations were found in NOTCH2 or MYD88. Four of the 5 patients with aggressive
disease had mutations in NOTCH1 (2 cases), TP53 (1 case), and MAP2K1 (1 case).
The progression-free survival of patients with mutated genes was significantly
shorter than in the unmutated (P=0.011). These findings show that SDRPL share
some mutated genes but not chromosomal alterations, with other splenic lymphomas,
that may confer a more aggressive behavior.
PMID- 26426383
TI - Idelalisib-associated Enterocolitis: Clinicopathologic Features and Distinction
From Other Enterocolitides.
AB - Idelalisib is a highly specific small-molecule phosphoinositide-3-kinase delta
inhibitor that was recently approved by the Food and Drug Administration for the
treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma and
follicular lymphoma. The known side effects of idelalisib include severe diarrhea
and colitis. Here we report the histologic findings in idelalisib-associated
enterocolitis in 11 patients with chronic lymphocytic leukemia or follicular
lymphoma receiving idelalisib over a 5-year period (2011 to 2015) at our
institution. All 11 patients were receiving idelalisib and underwent colonoscopy
for the evaluation of diarrhea. None of the patients had previously received a
stem cell transplant. Histologically, the colon biopsies in all 11 cases showed
some degree of apoptosis within crypts, with 5 cases showing moderate to severe
apoptosis involving the majority of the crypts with loss of goblet cells. No
viral inclusions were seen in any case and immunohistochemical stains for
cytomegalovirus performed in 9/11 cases were negative. All cases showed at least
focal acute cryptitis, and 8 of these cases showed mild architectural distortion.
Increased inflammation within the lamina propria was seen in 7 cases, and
increased intraepithelial lymphocytes within crypts was seen in 8 cases; the
lymphocytes were mostly T cells with a predominance of CD8 T cells, with the
majority expressing the alpha/beta T-cell receptor. Diagnoses of graft-versus
host disease, autoimmune enteropathy, infectious enterocolitis, and although
thought to be less likely, inflammatory bowel disease were considered in each
case. The presence of numerous intraepithelial lymphocytes in addition to severe
villous blunting and apoptosis in the small intestinal biopsies from a subset of
these patients additionally raised the possibility of autoimmune enteropathy,
common variable immunodeficiency, or less likely, celiac disease. Awareness of
the histologic features of idelalisib-associated enterocolitis is important to
distinguish it from potential mimics, particularly graft-versus-host disease,
autoimmune enteropathy, and cytomegalovirus/infectious enterocolitis.
PMID- 26426384
TI - Whole Mouse Brain Image Reconstruction from Serial Coronal Sections Using FIJI
(ImageJ).
AB - Whole-brain reconstruction of the mouse enables comprehensive analysis of the
distribution of neurochemical markers, the distribution of anterogradely labeled
axonal projections or retrogradely labeled neurons projecting to a specific brain
site, or the distribution of neurons displaying activity-related markers in
behavioral paradigms. This unit describes a method to produce whole-brain
reconstruction image sets from coronal brain sections with up to four fluorescent
markers using the freely available image-processing program FIJI (ImageJ).
PMID- 26426385
TI - Laser-Mediated Microlesions in Mouse Neocortex to Investigate Neuronal
Degeneration and Regeneration.
AB - In vivo two-photon (2P) imaging enables neural circuitry to be repeatedly
visualized in both normal conditions and following trauma. This protocol
describes how laser-mediated neuronal microlesions can be created in the cerebral
cortex using an ultrafast laser without causing a significant inflammatory
reaction or compromising the blood-brain barrier. Furthermore, directives are
provided for the acute and chronic in vivo imaging of the lesion site, as well as
for post-hoc analysis of the lesion site in fixed tissue, which can be correlated
with the live imaging phase.
PMID- 26426388
TI - Squaramide-catalysed asymmetric cascade aza-Michael/Michael addition reaction for
the synthesis of chiral trisubstituted pyrrolidines.
AB - A bifunctional squaramide catalysed aza-Michael/Michael cascade reaction between
nitroalkenes and tosylaminomethyl enones or enoates has been developed. This
organocatalytic cascade reaction provides easy access to highly functionalized
chiral pyrrolidines with a broad substrate scope, giving the desired products in
good yields (up to 99%) with good diastereoselectivities (up to 91 : 9 dr) and
excellent enantioselectivities (up to >99% ee) under mild conditions. This
protocol provides a straightforward entry to highly functionalized chiral
trisubstituted pyrrolidine derivatives from simple starting materials.
PMID- 26426387
TI - Implementation of isoniazid preventive therapy in an HIV clinic in Cambodia: high
rates of discontinuation when combined with antiretroviral therapy.
AB - OBJECTIVE: Data on feasibility and completion rates of isoniazid preventive
therapy (IPT) in HIV-infected patient in Asia are limited. Within a hospital
based HIV programme in Phnom Penh, Cambodia, we determined the proportion
completing IPT and reasons for non-completion. METHODS: Retrospective cohort
study using HIV/IPT programme data, including all adults starting IPT (300 mg/day
self-administered for 24 weeks) from February 2011 to March 2013. All patients
underwent symptom screening and further investigations as indicated. After ruling
out tuberculosis (TB), IPT was started, with monthly follow-up visits. As per
national guideline, IPT was only prescribed for ART-naive patients. IPT
completion was defined as taking IPT for at least 22 of the planned 24 weeks.
Stavudine/lamivudine/nevirapine was the preferential first-line ART regimen.
RESULTS: Among 445 ART-naive patients starting IPT (median age: 35 years (IQR: 31
43), median CD4 count 354 cells/MUl (IQR 215-545) and 288 (65%) were female), 214
(48%) started ART after a median of 4 weeks (IQR 2-6) on IPT ('concurrent ART').
Overall, 348 (78%) completed IPT. Among individuals with concurrent ART, the
completion rate was 73% (157/214). Those without concurrent ART had a higher
completion rate (83%; 191/231; P 0.017). The main reason for non-completion with
concurrent ART was drug toxicity (mainly hepatotoxicity/rash), occurring in 22%
(48/214). Without concurrent ART, the main reason for non-completion was loss to
follow-up (16/231; 7%). Fourteen (3%) patients were diagnosed with TB while on
IPT, of whom three had a positive TB culture at baseline. An additional 14 TB
cases were diagnosed after IPT completion; four were bacteriologically confirmed.
CONCLUSION: Although overall completion rates were acceptable, IPT
discontinuation due to drug toxicity was common in patients subsequently
initiating ART. Future studies should evaluate whether this relates to IPT, ARVs
or both, and whether the increased toxicity would justify delaying IPT initiation
until stabilisation on ART.
PMID- 26426386
TI - Use of Adeno-Associated and Herpes Simplex Viral Vectors for In Vivo Neuronal
Expression in Mice.
AB - Adeno-associated viruses and the herpes simplex virus are the two most widely
used vectors for the in vivo expression of exogenous genes. Advances in the
development of these vectors have enabled remarkable temporal and spatial control
of gene expression. This unit provides methods for storing, delivering, and
verifying expression of adeno-associated and herpes simplex viruses in the adult
mouse brain. It also describes important considerations for experiments using in
vivo expression of these viral vectors, including serotype and promoter
selection, as well as timing of expression. Additional protocols are provided
that describe methods for preliminary experiments to determine the appropriate
conditions for in vivo delivery.
PMID- 26426389
TI - Differential expression of CARMIL-family genes during zebrafish development.
AB - CARMILs are a conserved family of large multidomain proteins that regulate and
target actin assembly by interacting with actin capping protein (CP). Vertebrates
contain three highly conserved CARMIL isoforms encoded by three genes, whereas
lower organisms contain only one isoform and gene. In order to investigate the
functions of vertebrate CARMILs, we identified and characterized the three CARMIL
genes in zebrafish (Danio rerio). We isolated and sequenced complete and partial
cDNAs from embryos. The three genes display distinct spatial and temporal
expression patterns during development. Sequence and phylogenetic analyses of
cDNAs and predicted protein sequences reveal that the three zebrafish genes fall
into the three conserved isoform groups previously defined for other vertebrates,
which have isoform-specific and overlapping functions in human cultured cells.
These results provide new tools and offer insight into understanding the role of
the regulation of actin assembly dynamics during embryonic development and tissue
morphogenesis.
PMID- 26426390
TI - Targeted gene exchange in plant cells mediated by a zinc finger nuclease double
cut.
AB - Genome modification by homology-directed repair (HDR) is an attractive tool for
the controlled genetic manipulation of plants. Here, we report the HDR-mediated
gene exchange of expression cassettes in tobacco BY-2 cells using a designed zinc
finger nuclease (ZFN). The target contained a 7-kb fragment flanked by two ZFN
cutting sites. That fragment was replaced with a 4-kb donor cassette, which
integrates gene markers for selection (kanamycin resistance) and for scoring
targeting (red fluorescent protein, RFP). Candidates resulting from cassette
exchange were identified by molecular analysis of calli generated by
transformation via direct DNA delivery. The precision of HDR-mediated donor
integration was evaluated by Southern blot analysis, sequencing of the
integration locus and analysis of RFP fluorescence by flow cytometry. Screening
of 1326 kanamycin-resistant calli yielded 18 HDR events, 16 of which had a
perfect cassette exchange at the insert junction and 13 of which produced
functional RFP. Our results demonstrate that ZFN-based HDR can be used for high
frequency, precise, targeted exchange of fragments of sizes that are commercially
relevant in plants.
PMID- 26426391
TI - Controlling the Fluorescence Response of PET Sensors via the Metal-Ion pi
Contacting Ability of the Fluorophore: Coumarin, a Weaker pi Contacter.
AB - The pi-contact hypothesis, that quenching of the fluorescence of complexes of
photoinduced electron transfer sensors with heavy diamagnetic metal ions may be
caused by pi contacts between the metal ion and the fluorophore of the sensor, is
examined with a study of the fluorescent properties of the sensor 4-[[bis(2
pyridinylmethyl)amino]methyl]-6,7-dimethoxy-1-benzopyran-2-one (cdpa) and the
structures of its complexes with some metal ions. The coumarin-type fluorophore
of cdpa is a weaker pi-contact former than the anthracenyl fluorophore of the
analogue adpa (Inorg. Chem. 2014, 53, 9014): only Ag(I), the strongest pi contact
former, quenches the fluorescence of cdpa, apart from paramagnetic Cu(II) and
Ni(II), which quench fluorescence by a redox mechanism not requiring pi contacts.
The structures of [Ag(cdpa)NO3] (1), [Pb(cdpa)(NO3)2] (2), [Zn(cdpa)(NO3)2] (3),
[Cd(cdpa)Cl2]2 (4), [Cd(cdpa)2H2O](NO3)2 (5), and [Hg(cdpa)2H2O](NO3)2 (6) are
reported. Structure 1 shows that Ag(I) is the only metal ion studied that forms
pi contacts with the fluorophore of cdpa in the solid state: Ag...C eta(2) pi
contacts of 3.083 and 3.095 A, in line with quenching of the fluorescence of the
Ag(I)(cdpa) complex. In contrast, Pb(II), Zn(II), and Cd(II) show chelation
enhanced fluorescence in their cdpa complexes, and the structures of 2-4 show
that the fluorophore of cdpa in each case forms no pi contacts. By contrast, the
adpa complexes of Pb(II) and Cd(II) show pi contacts with its more strongly pi
contacting fluorophore (Inorg. Chem. 2014, 53, 9014). The structures of 5 and 6
show bis-complexes of cdpa: the coordination geometries of Cd(II) and Hg(II) are
discussed in relation to the number of covalently bound donor atoms present. The
preferred hapticity of pi-contacted metal ions is evaluated from the literature
structures, suggesting that d(10) metal ions such as Ag(I) and Hg(II), and
tetragonally distorted Cu(II) and Pd(II), prefer eta(1) and eta(2) pi contacts,
while more ionically bound metal ions such as K(I), Ba(II), and La(III), as well
as d(10)s(2) metal ions such as Tl(I), Pb(II), and Bi(III), prefer eta(6)
contacts.
PMID- 26426392
TI - Behavioral Evolution of Progressive Semantic Aphasia in Comparison with Nonfluent
Aphasia.
AB - BACKGROUND: Patients with primary progressive aphasia (PPA) usually develop
significant behavioral disturbances with progression of the disease. We tested
our clinical observation that development of disruptive agitation is more likely
in semantic than in nonfluent PPA and examined which clinical variables could be
associated with this behavior. METHODS: We retrospectively analyzed
neuropsychiatric scores and the need for behavioral treatments in semantic PPA (n
= 41) and nonfluent PPA (n = 39) cases and compared first (1-3 years since the
onset of symptoms) and last (5-13 years since the onset) evaluations. Clinical
variables and laterality of temporal atrophy were associated with symptoms in
semantic PPA cases. RESULTS: The semantic PPA group developed more frequent (p =
0.03) and intense agitation (p = 0.0008) and had a greater need for antipsychotic
drugs (p = 0.001) than the nonfluent PPA group. Presence of agitation was clearly
associated with psychotic symptoms (delusions/hallucinations) but was not
associated with gender, age at onset, duration of the disease, or laterality of
temporal atrophy. In contrast, nonfluent PPA cases were more frequently depressed
and treated with antidepressants (p = 0.0007). There were no differences in
anxiety, irritability, apathy, perseverations, hyperorality, or abnormal motor
behavior. CONCLUSIONS: Semantic PPA in advanced disease is frequently associated
with agitation and psychotic symptoms with fewer mood symptoms, while nonfluent
PPA maintains a high prevalence of depression. This implies different treatment
and care and support needs for each group.
PMID- 26426393
TI - A new method to evaluate the effects of shear on the skin.
AB - Currently, pressure ulcer preventive strategies focus mainly on pressure
redistribution. Little attention is paid to reduce the harmful effects of shear
force, because little is known about pathophysiological aspects of shear-force.
Even today, no method to measure the effects of shear-force on the skin is
available. Therefore, the aim of this study was to investigate the response to
shear-forces in terms of analyzing a noninvasive biomarker and reactive hyperemic
parameter measured at the skin of healthy participants. A physical model was
developed to produce a combination of pressure and shear or pressure alone on the
skin. Ten healthy male participants were included and pressure (3.9 kPa) and a
combined loading of pressure and shear (2.4 kPa + 14.5 N) was applied at the
volar aspect of the forearms for 15 and 30 minutes. A Sebutape sample was used to
collect IL-1alpha and total protein (TP) noninvasively. The reactive hyperemic
parameter was derived from a laser Doppler flowmeter. The increase in IL
1alpha/TP-ratio after a combined loading of pressure and shear for 30 minutes of
6.2 +/- 2.5 was significantly higher compared with all other test conditions (p <
0.05). The increase in cutaneous blood cell flux was already significantly higher
when a combined loading of pressure and shear was applied for 15 minutes compared
with pressure alone. These results shows that the IL-1alpha/TP-ratio and
cutaneous blood cell flux can be used as robust measures of the effect of shear
force on skin in humans. Therefore, this model can be used to evaluate materials
aimed at the reduction of shear.
PMID- 26426394
TI - Short-term carbon cycling responses of a mature eucalypt woodland to gradual
stepwise enrichment of atmospheric CO2 concentration.
AB - Projections of future climate are highly sensitive to uncertainties regarding
carbon (C) uptake and storage by terrestrial ecosystems. The Eucalyptus Free-Air
CO2 Enrichment (EucFACE) experiment was established to study the effects of
elevated atmospheric CO2 concentrations (eCO2 ) on a native mature eucalypt
woodland with low fertility soils in southeast Australia. In contrast to other
FACE experiments, the concentration of CO2 at EucFACE was increased gradually in
steps above ambient (+0, 30, 60, 90, 120, and 150 ppm CO2 above ambient of ~400
ppm), with each step lasting approximately 5 weeks. This provided a unique
opportunity to study the short-term (weeks to months) response of C cycle flux
components to eCO2 across a range of CO2 concentrations in an intact ecosystem.
Soil CO2 efflux (i.e., soil respiration or Rsoil ) increased in response to
initial enrichment (e.g., +30 and +60 ppm CO2 ) but did not continue to increase
as the CO2 enrichment was stepped up to higher concentrations. Light-saturated
photosynthesis of canopy leaves (Asat ) also showed similar stimulation by
elevated CO2 at +60 ppm as at +150 ppm CO2 . The lack of significant effects of
eCO2 on soil moisture, microbial biomass, or activity suggests that the increase
in Rsoil likely reflected increased root and rhizosphere respiration rather than
increased microbial decomposition of soil organic matter. This rapid increase in
Rsoil suggests that under eCO2, additional photosynthate was produced,
transported belowground, and respired. The consequences of this increased
belowground activity and whether it is sustained through time in mature
ecosystems under eCO2 are a priority for future research.
PMID- 26426395
TI - Myosin-Powered Membrane Compartment Drives Cytoplasmic Streaming, Cell Expansion
and Plant Development.
AB - Using genetic approaches, particle image velocimetry and an inert tracer of
cytoplasmic streaming, we have made a mechanistic connection between the motor
proteins (myosins XI), cargo transported by these motors (distinct endomembrane
compartment defined by membrane-anchored MyoB receptors) and the process of
cytoplasmic streaming in plant cells. It is shown that the MyoB compartment in
Nicotiana benthamiana is highly dynamic moving with the mean velocity of ~3
MUm/sec. In contrast, Golgi, mitochondria, peroxisomes, carrier vesicles and a
cytosol flow tracer share distinct velocity profile with mean velocities of 0.6
1.5 MUm/sec. Dominant negative inhibition of the myosins XI or MyoB receptors
using overexpression of the N. benthamiana myosin cargo-binding domain or MyoB
myosin-binding domain, respectively, resulted in velocity reduction for not only
the MyoB compartment, but also each of the tested organelles, vesicles and
cytoplasmic streaming. Furthermore, the extents of this reduction were similar
for each of these compartments suggesting that MyoB compartment plays primary
role in cytosol dynamics. Using gene knockout analysis in Arabidopsis thaliana,
it is demonstrated that inactivation of MyoB1-4 results in reduced velocity of
mitochondria implying slower cytoplasmic streaming. It is also shown that myosins
XI and MyoB receptors genetically interact to contribute to cell expansion, plant
growth, morphogenesis and proper onset of flowering. These results support a
model according to which myosin-dependent, MyoB receptor-mediated transport of a
specialized membrane compartment that is conserved in all land plants drives
cytoplasmic streaming that carries organelles and vesicles and facilitates cell
growth and plant development.
PMID- 26426396
TI - Microarray Analysis of the Gene Expression Profile and Lipid Metabolism in Fat-1
Transgenic Cattle.
AB - Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) are beneficial for human
health. However, humans and mammals are unable to synthesize n-3 PUFAs because
they lack the n-3 desaturase gene fat-1 and must therefore obtain this type of
fatty acid through their diet. Through the production of fat-1 transgenic
animals, it is possible to obtain animal products that are rich in n-3 PUFAs,
such as meat and milk. The aim of this study was to analyze the gene expression
profile and the mechanism of lipid metabolism in fat-1 transgenic cattle and to
accumulate important basic data that are required to obtain more efficient fat-1
transgenic cattle. Transcriptome profiling of fat-1 transgenic and wild-type
cattle identified differentially expressed genes that are involved in 90
biological pathways, eight pathways of which were related to lipid metabolism
processes 36 genes of which were related to lipid metabolism. This analysis also
identified 11 significantly enriched genes that were involved in the peroxisome
proliferator-activated receptor signaling pathway. These findings were verified
by quantitative polymerase chain reaction. The information obtained in this study
indicated that the introduction of an exogenous fat-1 gene into cattle affects
the gene expression profile and the process of lipid metabolism in these animals.
These results may provide important insights into how an exogenous fat-1 gene
synthesizes n-3 PUFAs in transgenic cattle and other mammals.
PMID- 26426397
TI - Micro-RNA Binding Site Polymorphisms in the WFS1 Gene Are Risk Factors of
Diabetes Mellitus.
AB - The absolute or relative lack of insulin is the key factor in the pathogenesis of
diabetes mellitus. Although the connection between loss of function mutations of
the WFS1 gene and DIDMOAD-syndrome including diabetes mellitus underpins the
significance of wolframin in the pathogenesis, exact role of WFS1 polymorphic
variants in the development of type 1 and type 2 diabetes has not been discovered
yet. In this analysis, 787 patients with diabetes and 900 healthy people
participated. Genotyping of the 7 WFS1 SNPs was carried out by TaqMan assays.
Association study was performed by chi2-test in combination with correction for
multiple testing. For functional analysis, the entire 3' UTR of the WFS1 gene was
subcloned in a pMIR-Report plasmid and relative luciferase activities were
determined. Linkage disequilibrium analysis showed a generally high LD within the
investigated region, however the rs1046322 locus was not in LD with the other
SNPs. The two miR-SNPs, rs1046322 and rs9457 showed significant association with
T1DM and T2DM, respectively. Haplotype analysis also confirmed the association
between the 3' UTR loci and both disease types. In vitro experiments showed that
miR-185 reduces the amount of the resulting protein, and rs9457 miRSNP
significantly influences the rate of reduction in a luciferase reporter assay.
Genetic variants of the WFS1 gene might contribute to the genetic risk of T1DM
and T2DM. Furthermore demonstrating the effect of rs9457 in binding of miR-185,
we suggest that the optimal level of wolframin protein, potentially influenced by
miR-regulation, is crucial in normal beta cell function.
PMID- 26426399
TI - A Puzzle in the Carotid Space. Ancient schwannoma.
PMID- 26426398
TI - Estimation of apparent binding constant of complexes of selected acyclic
nucleoside phosphonates with beta-cyclodextrin by affinity capillary
electrophoresis.
AB - Affinity capillary electrophoresis (ACE) has been applied to estimation of
apparent binding constant of complexes of (R,S)-enantiomers of selected acyclic
nucleoside phosphonates (ANPs) with chiral selector beta-cyclodextrin (betaCD) in
aqueous alkaline medium. The noncovalent interactions of five pairs of (R,S)
enantiomers of ANPs-based antiviral drugs and their derivatives with betaCD were
investigated in the background electrolyte (BGE) composed of 35 or 50 mM sodium
tetraborate, pH 10.0, and containing variable concentration (0-25 mM) of betaCD.
The apparent binding constants of the complexes of (R,S)-enantiomers of ANPs with
betaCD were estimated from the dependence of effective electrophoretic mobilities
of (R,S)-enantiomers of ANPs (measured simultaneously by ACE at constant
reference temperature 25 degrees C inside the capillary) on the concentration of
betaCD in the BGE using different nonlinear and linear calculation methodologies.
Nonlinear regression analysis provided more precise and accurate values of the
binding constants and a higher correlation coefficient as compared to the
regression analysis of the three linearized plots of the effective mobility
dependence on betaCD concentration in the BGE. The complexes of (R,S)-enantiomers
of ANPs with betaCD have been found to be relatively weak - their apparent
binding constants determined by the nonlinear regression analysis were in the
range 13.3-46.4 L/mol whereas the values from the linearized plots spanned the
interval 12.3-55.2 L/mol.
PMID- 26426400
TI - Relationship of residency program characteristics with pass rate of the American
Board of Internal Medicine certifying exam.
AB - OBJECTIVES: To evaluate the relationship between the pass rate of the American
Board of Internal Medicine (ABIM) certifying exam and the characteristics of
residency programs. METHODS: The study used a retrospective, cross-sectional
design with publicly available data from the ABIM and the Fellowship and
Residency Electronic Interactive Database. All categorical residency programs
with reported pass rates were included. Using univariate and multivariate, linear
regression analyses, I analyzed how 69 factors (e.g., location, general
information, number of faculty and trainees, work schedule, educational
environment) are related to the pass rate. RESULTS: Of 371 programs, only one
region had a significantly different pass rate from the other regions; however,
as no other characteristics were reported in this region, I excluded program
location from further analysis. In the multivariate analysis, pass rate was
significantly associated with four program characteristics: ratio of full-time
equivalent paid faculty to positions, percentage of osteopathic doctors, formal
mentoring program, and on-site child care (OCC). Numerous factors were not
associated at all, including minimum exam scores, salary, vacation days, and
average hours per week. CONCLUSIONS: As shown through the ratio of full-time
equivalent paid faculty to positions and whether there was a formal mentoring
program, a highly supervised training experience was strongly associated with the
pass rate. In contrast, percentage of osteopathic doctors was inversely related
to the pass rate. Programs with OCC significantly outperformed programs without
OCC. This study suggested that enhancing supervision of training programs and
offering parental support may help attract and produce competitive residents.
PMID- 26426401
TI - Gamification in medical education.
PMID- 26426402
TI - Non-invasive assessment of liver fibrosis in chronic viral hepatitis.
AB - BACKGROUND: Hyaluronic acid (HA), ASAT to Platelet Ratio Index (APRI), ASAT/ALAT
ratio, Fibrosis 4 score (FIB4) and FibroScan were studied as non-invasive markers
of liver fibrosis (F) in chronic viral hepatitis B (CHB) and C (CHC), in an
attempt to avoid the complications of liver puncture biopsy, considered the gold
standard in the evaluation of F. The aim of our research was to study whether HA,
APRI, ASAT/ALAT ratio, FIB4 and FibroScan are useful non-invasive markers in
predicting severe F in Romanian patients. PATIENTS AND METHODS: This was a
prospective multicenter transversal and observational study, which included 76
patients with CHB/CHC. The independent effect of studied markers was tested using
multiple binary logistic regression. RESULTS: In patients with CHB and CHC, the
APRI cut-off value for F4 was 0.70 ng/mL (Se = 77%, Sp = 78%), the FIB4 cut-off
value was 2.01 (Se = 77%, Sp = 69%), and the FibroScan cut-off value was 13.15
(Se = 92%, Sp = 88%). For patients with CHB/CHC, there was a significant linear
positive correlation between F and HA (r = 0.42, P = 0.001), FibroScan (r = 0.67,
P < 0.001), APRI (r = 0.46, P < 0.001) and FIB4 (r = 0.51, P < 0.001).
Considering age, sex and body mass index as possible confounding factors or
covariates in multivariable logistic modelling, FibroScan was the unique test
that able to significantly highlight the presence of F4 score in CHB/CHC patients
(P = 0.009) while FIB4 test seems to have a tendency to statistical significance.
CONCLUSION: FibroScan, APRI and FIB4 are useful non-invasive tests for the
evaluation of F4 in patients with CHB and CHC.
PMID- 26426403
TI - Details of Glaucomatous Damage Are Better Seen on OCT En Face Images Than on OCT
Retinal Nerve Fiber Layer Thickness Maps.
AB - PURPOSE: High-resolution images of glaucomatous damage to the retinal nerve fiber
layer (RNFL) were obtained with an adaptive optics-scanning light ophthalmoscope
(AO-SLO) and used as a basis for comparisons between en face slab images and
thickness maps derived from optical coherence tomography (OCT) scans. METHODS:
Wide-field (9 * 12 mm) cube scans were obtained with swept-source OCT (DRI-OCT)
from six eyes of six patients. All eyes had a deep defect near fixation as seen
on a 10-2 visual field test. Optical coherence tomography en face images, based
on the average reflectance intensity, were generated (ATL 3D-Suite) from 52-MUm
slabs just below the vitreal border of the inner limiting membrane. The RNFL
thickness maps were generated from the same OCT data. Both were compared with the
AO-SLO peripapillary images that were previously obtained. RESULTS: On AO-SLO
images, three eyes showed small regions of preserved and/or missing RNFL bundles
within the affected region. Details in these regions were seen on the OCT en face
images but not on the RNFL thickness maps. In addition, in the healthier hemi
retinas of two eyes, there were darker, arcuate-shaped regions on en face images
that corresponded to abnormalities seen on AO-SLO. These were not seen on RNFL
thickness maps. CONCLUSIONS: Details of local glaucomatous damage, missing or
easily overlooked on traditional OCT RNFL thickness analysis used in clinical OCT
reports, were seen on OCT en face images based on the average reflectance
intensity. While more work is needed, it is likely that en face slab imaging has
a role in the clinical management of glaucoma.
PMID- 26426404
TI - Compartmental Innervation of the Superior Oblique Muscle in Mammals.
AB - PURPOSE: Intramuscular innervation of mammalian horizontal rectus extraocular
muscles (EOMs) is compartmental. We sought evidence of similar compartmental
innervation of the superior oblique (SO) muscle. METHODS: Three fresh bovine
orbits and one human orbit were dissected to trace continuity of SO muscle and
tendon fibers to the scleral insertions. Whole orbits were also obtained from
four humans (two adults, a 17-month-old child, and a 33-week stillborn fetus),
two rhesus monkeys, one rabbit, and one cow. Orbits were formalin fixed, embedded
whole in paraffin, serially sectioned in the coronal plane at 10-MUm thickness,
and stained with Masson trichrome. Extraocular muscle fibers and branches of the
trochlear nerve (CN4) were traced in serial sections and reconstructed in three
dimensions. RESULTS: In the human, the lateral SO belly is in continuity with
tendon fibers inserting more posteriorly on the sclera for infraducting
mechanical advantage, while the medial belly is continuous with anteriorly
inserting fibers having mechanical advantage for incycloduction. Fibers in the
monkey superior SO insert more posteriorly on the sclera to favor infraduction,
while the inferior portion inserts more anteriorly to favor incycloduction. In
all species, CN4 bifurcates prior to penetrating the SO belly. Each branch
innervates a nonoverlapping compartment of EOM fibers, consisting of medial and
lateral compartments in humans and monkeys, and superior and inferior
compartments in cows and rabbits. CONCLUSIONS: The SO muscle of humans and other
mammals is compartmentally innervated in a manner that could permit separate CN4
branches to selectively influence vertical versus torsional action.
PMID- 26426405
TI - Pediatric deceased donor renal transplantation: An approach to decision making
II. Acceptability of a deceased donor kidney for a child, a snap decision at 3
AM.
AB - Allocation of deceased donor kidneys is based on several criteria; however, the
final decision to accept or reject the offered kidney is made by the potential
recipient's transplant team (surgeon/nephrologist). Several considerations
including assessment of the donor quality, the HLA match between the donor and
the recipient, several recipient factors, the geographical location of the
recipient, and the organ all affect the decision of whether or not to finally
accept the organ for a particular recipient. This decision needs to be made
quickly, often on the spot. Maximizing the benefit from this scarce resource
raises difficult ethical issues. The philosophies of equity and utility are often
competing. This article will discuss the several considerations for the pediatric
nephrologist while accepting a deceased donor kidney for a particular pediatric
patient.
PMID- 26426407
TI - MULTIFOCAL RETINAL INFILTRATES WITH PHLEBITIS AND OPTIC NEUROPATHY IN AN HIV
POSITIVE PEDIATRIC PATIENT.
AB - PURPOSE: To describe an unusual presentation of bilateral HIV-associated
multifocal retinal infiltrates with phlebitis and optic neuropathy in a pediatric
patient from Zimbabwe, Africa. METHODS: Retrospective case report of a 15-year
old boy from Zimbabwe, Africa. RESULTS: The patient was found to have bilateral
vitritis, multifocal retinitis with phlebitis, and optic neuropathy in the
setting of previously unrecognized HIV infection. Vision improved and the
clinical findings resolved after treatment with intravenous corticosteroids and
highly active retroviral therapy (HAART). CONCLUSION: The authors describe the
occurrence and treatment of bilateral, HIV-associated multifocal retinal
infiltrates with phlebitis and HIV-associated optic neuropathy in a pediatric
patient from Zimbabwe, Africa.
PMID- 26426406
TI - Failure of Ovarian Suppression With Gonadotropin-Releasing Hormone Analogs to
Preserve Fertility: An Assessment Based on the Quality of Evidence.
PMID- 26426408
TI - SEROUS NEUROSENSORY RETINAL DETACHMENT ASSOCIATED WITH ATYPICAL COGAN SYNDROME: A
CASE REPORT.
AB - PURPOSE: To present a case of a 71-year-old woman with possible focal choroiditis
and secondary serous neurosensory retinal detachment associated with atypical
Cogan syndrome. METHODS: Retrospective case report. RESULTS: On initial
evaluation, the patient had decreased vision with photopsias and distortion in
the affected eye. Her history revealed 3 years of preexisting neurosensory
hearing loss and corneal scarring in the affected eye. Examination findings were
significant for unilateral interstitial keratitis and focal macular neurosensory
retinal detachment. Fluorescein and indocyanine green angiography demonstrated
focal macular leakage and staining. Treatment with intravitreal and periocular
steroid injections resulted in complete resolution of the subretinal fluid and
visual improvement. CONCLUSION: Posterior segment manifestations associated with
Cogan syndrome are exceedingly rare. This is the first known case of a serous
neurosensory retinal detachment from suspected choroidal inflammation associated
with Cogan syndrome. Prompt recognition and treatment with corticosteroids may
result in anatomical and functional visual improvement, as in this case.
PMID- 26426410
TI - Organocatalytic multicomponent synthesis of polysubstituted pyrroles from 1,2
diones, aldehydes and arylamines.
AB - We have developed an organocatalyzed three-component reaction of 1,2-diones,
aldehydes and arylamines, which provides an efficient approach to access
polysubstituted pyrroles. In the catalysis of 4-methylbenzenesulfonic acid
monohydrate, the reactions of a wide range of 1,2-diones, arylamines and
aldehydes took place smoothly to generate the corresponding polysubstituted
pyrroles in acceptable to good yields under mild reaction conditions.
PMID- 26426412
TI - Will the attributes of multiparametric MRI permit the creation of a new approach
to therapy?
AB - PURPOSE OF REVIEW: To explore the concept that MRI can be used to permit a new
approach to therapy of localized prostate cancer. RECENT FINDINGS: With the
development of multiparametric MRI, we can characterize cancer within the
prostate, in terms of location, volume and radiological phenotype. The use of
volume and location to identify candidates for focal ablative therapy is well
established.The radiological phenotype of a tumour includes the vascularity and
diffusion characteristics of that tumour. These characteristics may help us to
develop novel interventions to target particular characteristics of a tumour.The
assessment of novel interventions such as sulforaphanes found in broccoli, and
common medications used for other diseases such as aspirin and metformin
typically use population based studies, or repeat biopsy studies in large groups
of men on active surveillance. MRI, with its accurate detection of change in
visible tumour over a 6-month period, could allow rapid noninvasive assessment of
a novel intervention. SUMMARY: MRI could be used to allow the rapid and efficient
assessment of dietary and other interventions to identify candidates for
assessment in larger studies and potentially, to identify subgroups of tumours
which would be most suited to a given intervention.
PMID- 26426413
TI - Continent cutaneous diversion.
AB - PURPOSE OF REVIEW: This article updates the recently reported intermediate to
long-term results with the most commonly used forms of continent cutaneous
urinary diversion, and to discuss approaches to early and late complications.
RECENT FINDINGS: Many variations on construction of a continent cutaneous
diversion have been described. Results with large series of patients demonstrate
acceptable results with all of them, but with a significant revision rate. Long
term complication rates and adaptation to robotic approaches have recently been
described. SUMMARY: Continent cutaneous diversion is rarely offered in the USA to
patients undergoing cystectomy except in a few centers. Most studies have found a
high complication rate and need for revision surgery in 10-20% of patients.
However, functional results are acceptable and many patients are willing to
accept the complications in exchange for avoiding an external appliance.
PMID- 26426415
TI - Recent advances in energy transfer in bulk and nanoscale luminescent materials:
from spectroscopy to applications.
AB - Transfer of energy occurs endlessly in our universe by means of radiation.
Compared to energy transfer (ET) in free space, in solid state materials the
transfer of energy occurs in a rather confined manner, which is usually mediated
by real or virtual particles, including not only photons, but also electrons,
phonons, and excitons. In the present review, we discuss the recent advances in
optical ET by resonance mediated with photons in solid materials as well as their
nanoscale counterparts, with focus on the photoluminescence behavior pertaining
to ET between optically active centers, such as rare earth (RE) ions. This review
begins with a brief discussion on the classification of optical ET together with
an overview of the theoretical formulations and experimental method for the
examination of ET. We will then present a comprehensive discussion on the ET in
practical systems in which normal photoluminescence, upconversion and quantum
cutting resulted from ET involving metal ions, QDs, organic species, 2D materials
and plasmonic nanostructures. Diverse ET systems are therefore simply categorized
into cases of ion-ion interactions and non-ion interactions. Special attention
has been paid to the progress in the manipulation of spatially confined ET in
nanostructured systems including core-shell structures, as well as the ET in
multiple exciton generation found in QDs and organic molecules, which behave
quite similarly to resonance ET between metal ion centers. Afterwards, we will
discuss the broad spectrum of applications of ET in the aforementioned systems,
including solid state lighting, solar energy utilization, bio-imaging and
diagnosis, and sensing. In the closing part, along with a short summary, we
discuss further research focus regarding the problems and possible future
directions of optical ET in solids.
PMID- 26426416
TI - Bridging the gap between interviewer and interviewee: developing an interview
guide for individual interviews by means of a focus group.
AB - BACKGROUND: In developing an interview guide, pre-existing knowledge about the
research topic is essential. In a recent study, we were interested in exploring
the experiences of weight changes among women treated for breast cancer using
individual interviews. However, to develop an interview guide for the individual
interviews that covered relevant thematic and dynamic dimensions, we found
existing literature insufficient. Thus, we turned our attention to the benefit of
the focus group method. OBJECTIVES: This study aims to discuss how a focus group
prior to individual interviews may contribute in developing the thematic
dimension and translating the dynamic dimension of an interview guide into
everyday language. METHODS: We conducted one focus group interview of five women
treated for breast cancer with experiences in weight changes. Data were analysed
using content and conversation analysis and discussed with relevant literature on
interview guide development. ETHICS: The study is approved by the Danish Data
Protection Agency (2008-58-0028) and follows the ethical guidelines for
qualitative research. RESULTS: Data generation and analysis resulted in themes
for the thematic dimension, as well as three dynamic areas to consider in the
individual interviews to bridge the gap between the interviewer and the
interviewee. The dynamic areas are as follows: The use of words, images and
metaphors - a shield and self-protection, Multiple meanings to explore and
Staying close to the everyday language. CONCLUSION: The analysis made us more
familiar with the content and meaning of weight changes among breast cancer
survivors. Furthermore, it provided images and metaphors, multiple meanings and a
sense of the women's everyday language that calls for an open interview frame to
be used in subsequent individual interviews.
PMID- 26426411
TI - Single-Molecule Sequencing Reveals Estrogen-Regulated Clinically Relevant lncRNAs
in Breast Cancer.
AB - Estrogen receptor (ER)alpha-positive tumors are commonly treated with ERalpha
antagonists or inhibitors of estrogen synthesis, but most tumors develop
resistance, and we need to better understand the pathways that underlie the
proliferative and tumorigenic role of this estrogen-activated transcription
factor. We here present the first single-molecule sequencing of the estradiol
induced ERalpha transcriptome in the luminal A-type human breast cancer cell
lines MCF7 and T47D. Sequencing libraries were prepared from the polyadenylated
RNA fraction after 8 hours of estrogen or vehicle treatment. Single-molecule
sequencing was carried out in biological and technical replicates and
differentially expressed genes were defined and analyzed for enriched processes.
Correlation analysis with clinical expression and survival were performed, and
follow-up experiments carried out using time series, chromatin
immunoprecipitation and quantitative real-time PCR. We uncovered that ERalpha in
addition to regulating approximately 2000 protein-coding genes, also regulated up
to 1000 long noncoding RNAs (lncRNAs). Most of these were up-regulated, and 178
lncRNAs were regulated in both cell lines. We demonstrate that Long Intergenic
Non-protein Coding RNA 1016 (LINC01016) and LINC00160 are direct transcriptional
targets of ERalpha, correlate with ERalpha expression in clinical samples, and
show prognostic significance in relation to breast cancer survival. We show that
silencing of LINC00160 results in reduced proliferation, demonstrating that
lncRNA expression have functional consequences. Our findings suggest that ERalpha
regulation of lncRNAs is clinically relevant and that their functions and
potential use as biomarkers for endocrine response are important to explore.
PMID- 26426409
TI - Behavioral and brain asymmetries in primates: a preliminary evaluation of two
evolutionary hypotheses.
AB - Contrary to many historical views, recent evidence suggests that species-level
behavioral and brain asymmetries are evident in nonhuman species. Here, we
briefly present evidence of behavioral, perceptual, cognitive, functional, and
neuroanatomical asymmetries in nonhuman primates. In addition, we describe two
historical accounts of the evolutionary origins of hemispheric specialization and
present data from nonhuman primates that address these specific theories.
Specifically, we first discuss the evidence that genes play specific roles in
determining left-right differences in anatomical and functional asymmetries in
primates. We next consider and present data on the hypothesis that hemispheric
specialization evolved as a by-product of increasing brain size relative to the
surface area of the corpus callosum in different primate species. Last, we
discuss some of the challenges in the study of hemispheric specialization in
primates and offer some suggestions on how to advance the field.
PMID- 26426417
TI - A knowledge-based molecular screen uncovers a broad-spectrum OsSWEET14 resistance
allele to bacterial blight from wild rice.
AB - Transcription activator-like (TAL) effectors are type III-delivered transcription
factors that enhance the virulence of plant pathogenic Xanthomonas species
through the activation of host susceptibility (S) genes. TAL effectors recognize
their DNA target(s) via a partially degenerate code, whereby modular repeats in
the TAL effector bind to nucleotide sequences in the host promoter. Although this
knowledge has greatly facilitated our power to identify new S genes, it can also
be easily used to screen plant genomes for variations in TAL effector target
sequences and to predict for loss-of-function gene candidates in silico. In a
proof-of-principle experiment, we screened a germplasm of 169 rice accessions for
polymorphism in the promoter of the major bacterial blight susceptibility S gene
OsSWEET14, which encodes a sugar transporter targeted by numerous strains of
Xanthomonas oryzae pv. oryzae. We identified a single allele with a deletion of
18 bp overlapping with the binding sites targeted by several TAL effectors known
to activate the gene. We show that this allele, which we call xa41(t), confers
resistance against half of the tested Xoo strains, representative of various
geographic origins and genetic lineages, highlighting the selective pressure on
the pathogen to accommodate OsSWEET14 polymorphism, and reciprocally the apparent
limited possibilities for the host to create variability at this particular S
gene. Analysis of xa41(t) conservation across the Oryza genus enabled us to
hypothesize scenarios as to its evolutionary history, prior to and during
domestication. Our findings demonstrate that resistance through TAL effector
dependent loss of S-gene expression can be greatly fostered upon knowledge-based
molecular screening of a large collection of host plants.
PMID- 26426418
TI - Behavior of Kinesin Driven Quantum Dots Trapped in a Microtubule Loop.
AB - We report the observation of kinesin driven quantum dots (QDs) trapped in a
microtubule loop, allowing the investigation of moving QDs for a long time and an
unprecedented long distance. The QD conjugates did not depart from our
observational field of view, enabling the tracking of specific conjugates for
more than 5 min. The unusually long run length and the periodicity caused by the
loop track allow comparing and studying the trajectory of the kinesin driven QDs
for more than 2 full laps, i.e., about 70 MUm, enabling a statistical analysis of
interactions of the same kinesin driven object with the same obstacle. The
trajectories were extracted and analyzed from kymographs with a newly developed
algorithm. Despite dispersion, several repetitive trajectory patterns can be
identified. A method evaluating the similarity is introduced allowing a
quantitative comparison between the trajectories. The velocity variations appear
strongly correlated to the presence of obstacles. We discuss the reasons making
this long continuous travel distances on the loop track possible.
PMID- 26426419
TI - Highly-efficient and versatile fluorous-tagged Cu(I)-catalyzed azide-alkyne
cycloaddition ligand for preparing bioconjugates.
AB - A novel ligand (FBTTBE) for Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC)
has been developed, which demonstrates not only superior catalytic efficiency but
also the ease of removing toxic copper species. FBTTBE has also been successfully
applied in the synthesis of radiometal-labeled peptide and antibody without
observable transchelation with the non-radioactive Cu(i) catalyst.
PMID- 26426420
TI - Core-Cone Structured Monodispersed Mesoporous Silica Nanoparticles with Ultra
large Cavity for Protein Delivery.
AB - A new type of monodispersed mesoporous silica nanoparticles with a core-cone
structure (MSN-CC) has been synthesized. The large cone-shaped pores are formed
by silica lamellae closely packed encircling a spherical core, showing a
structure similar to the flower dahlia. MSN-CC has a large pore size of 45 nm and
a high pore volume of 2.59 cm(3) g(-1). MSN-CC demonstrates a high loading
capacity of large proteins and successfully delivers active beta-galactosidase
into cells, showing their potential as efficient nanocarriers for the cellular
delivery of proteins with large molecular weights.
PMID- 26426421
TI - Efficacy of a Community-Based Physical Activity Program KM2H2 for Stroke and
Heart Attack Prevention among Senior Hypertensive Patients: A Cluster Randomized
Controlled Phase-II Trial.
AB - OBJECTIVE: To evaluate the efficacy of the program Keep Moving toward Healthy
Heart and Healthy Brain (KM2H2) in encouraging physical activities for the
prevention of heart attack and stroke among hypertensive patients enrolled in the
Community-Based Hypertension Control Program (CBHCP). DESIGN: Cluster randomized
controlled trial with three waves of longitudinal assessments at baseline, 3 and
6 months post intervention. SETTING: Community-based and patient-centered self
care for behavioral intervention in urban settings of China. PARTICIPANTS: A
total of 450 participants diagnosed with hypertension from 12 community health
centers in Wuhan, China were recruited, and were randomly assigned by center to
receive either KM2H2 plus standard CBHCP care (6 centers and 232 patients) or the
standard care only (6 centers and 218 patients). INTERVENTION: KM2H2 is a
behavioral intervention guided by the Transtheoretical Model, the Model of
Personalized Medicine and Social Capital Theory. It consists of six intervention
sessions and two booster sessions engineered in a progressive manner. The purpose
is to motivate and maintain physical activities for the prevention of heart
attack and stroke. OUTCOME MEASURES: Heart attack and stroke (clinically
diagnosed, primary outcome), blood pressure (measured, secondary outcome), and
physical activity (self-report, tertiary outcome) were assessed at the individual
level during the baseline, 3- and 6-month post-intervention. RESULTS: Relative to
the standard care, receiving KM2H2 was associated with significant reductions in
the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs.
9.90%, p<0.05), and moderate reduction in blood pressure (-3.72 mmHg in DBP and
2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in
physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95%
CI: 0.04, 0.85) post-intervention, respectively. CONCLUSION: The program KM2H2 is
efficacious to reduce the risk of heart attack and stroke among senior patients
who are on anti-hypertensive medication. Findings of this study provide solid
data supporting a formal phase-III trial to establish the effectiveness of KM2H2
for use in community settings for prevention. TRIAL REGISTRATION: ISRCTN Register
ISRCTN12608966.
PMID- 26426422
TI - A Novel C-Terminal CIB2 (Calcium and Integrin Binding Protein 2) Mutation
Associated with Non-Syndromic Hearing Loss in a Hispanic Family.
AB - Hearing loss is a complex disorder caused by both genetic and environmental
factors. Previously, mutations in CIB2 have been identified as a common cause of
genetic hearing loss in Pakistani and Turkish populations. Here we report a novel
(c.556C>T; p.(Arg186Trp)) transition mutation in the CIB2 gene identified through
whole exome sequencing (WES) in a Caribbean Hispanic family with non-syndromic
hearing loss. CIB2 belongs to the family of calcium-and integrin-binding (CIB)
proteins. The carboxy-termini of CIB proteins are associated with calcium binding
and intracellular signaling. The p.(Arg186Trp) mutation is localized within
predicted type II PDZ binding ligand at the carboxy terminus. Our ex vivo studies
revealed that the mutation did not alter the interactions of CIB2 with Whirlin,
nor its targeting to the tips of hair cell stereocilia. However, we found that
the mutation disrupts inhibition of ATP-induced Ca2+ responses by CIB2 in a
heterologous expression system. Our findings support p.(Arg186Trp) mutation as a
cause for hearing loss in this Hispanic family. In addition, it further
highlights the necessity of the calcium binding property of CIB2 for normal
hearing.
PMID- 26426423
TI - Rapamycin Promotes Mouse 4T1 Tumor Metastasis that Can Be Reversed by a Dendritic
Cell-Based Vaccine.
AB - Suppression of tumor metastasis is a key strategy for successful cancer
interventions. Previous studies indicated that rapamycin (sirolimus) may promote
tumor regression activity or enhance immune response against tumor targets.
However, rapamycin also exhibits immunosuppressant effects and is hence used
clinically as an organ transplantation drug. We hypothesized that the
immunosuppressive activities of rapamycin might also negatively mediate host
immunity, resulting in promotion of tumor metastasis. In this study, the effects
of rapamycin and phytochemical shikonin were investigated in vitro and in vivo in
a 4T1 mouse mammary tumor model through quantitative assessment of immunogenic
cell death (ICD), autophagy, tumor growth and metastasis. Tumor-bearing mice were
immunized with test vaccines to monitor their effect on tumor metastasis. We
found that intraperitoneal (ip) administration of rapamycin after a tumor
resection surgery drastically increased the metastatic activity of 4T1 tumors.
Possible correlation of this finding to human cancers was suggested by
epidemiological analysis of data from Taiwan's National Health Insurance Research
Database (NHIRD). Since our previous studies showed that modified tumor cell
lysate (TCL)-pulsed, dendritic cell (DC)-based cancer vaccines can effectively
suppress metastasis in mouse tumor models, we assessed whether such vaccines may
help offset this rapamycin-promoted metastasis. We observed that shikonin
efficiently induced ICD of 4T1 cells in culture, and DC vaccines pulsed with
shikonin-treated TCL (SK-TCL-DC) significantly suppressed rapamycin-enhanced
metastasis and Treg cell expansion in test mice. In conclusion, rapamycin
treatment in mice (and perhaps in humans) promotes metastasis and the effect may
be offset by treatment with a DC-based cancer vaccine.
PMID- 26426424
TI - Multi-probe relaxation dispersion measurements increase sensitivity to protein
dynamics.
AB - Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion measurements are a
valuable tool for the characterization of structural transitions on the micro
millisecond timescale. While the measurement of (15)N relaxation dispersion is
now routine, the measurements with alternative nuclei remain limited. Here we
report (15)N as well as (1)H R2 relaxation dispersion measurements of the
N23PP/S148A "dynamic knockout" mutant of dihydrofolate reductase. The (1)H
dispersion measurements are complementary to (15)N data as many additional
residues are observed to have dispersive behavior for the (1)H nucleus.
Simultaneous fitting of the dispersion profiles for the two nuclei increases the
accuracy of exchange parameters determined for individual residues and clustered
groups of residues. The different sensitivity of the two nuclei to changes in
backbone torsional angles, ring currents, and hydrogen bonding effects provides
important insights into the nature of the structural changes that take place
during the exchange process. We observe clear evidence of direct and indirect
hydrogen bond effects for the (15)N and (1)H chemical shift changes in the active
site, modulation of ring current shielding in the CD-loop and backbone torsional
changes in a cluster of residues associated with the C-terminus. This work
demonstrates the power of combined (1)H and (15)N probes for the study of
backbone dynamics on the micro-millisecond timescale though the analysis of
chemical shift changes.
PMID- 26426425
TI - Supracerebellar infratentorial approach with paramedian expansion for posterior
third ventricular and pineal region lesions.
AB - BACKGROUND: Surgical treatment for lesions in the posterior third ventricle is
technically challenging. Surgical approaches to this area carries a risk of both
venous and neural injury, with subsequent morbidity. Several approaches are used
to reach the pineal region. The supracerebellar infratentorial approach is the
commonly approach used for such lesions. OBJECTIVES: This work describes adding a
paramedian expansion to the "classical median supracerebellar infratentorial
approach" for posterior third ventricular and pineal region lesions with lateral
expansion. This study discusses the results concerning the extent of removal and
surgical complications for this procedure. Contralateral paramedian expansion is
used for targeting lesions inside the posterior third ventricle extending to the
lateral ventricular wall and thalamus. Ipsilateral paramedian expansion was used
in resecting collicular lesions. METHODS: The authors operated on patients
suffering from lesions in the pineal region using a paramedian expanded SCTT
approach between 2007 and 2014. The prone position was used in 25 cases. A
typical median suboccipital craniotomy with a paramedian expansion was performed.
Ipsilateral expansion of the approach has been used for targeting lesions in the
pineal region but outside the posterior third ventricle. Contralateral expansion
provides a direct view of the lateral walls of the third ventricle. RESULTS: We
encountered 28 cases of different pathologies: fourteen patients suffered from
pineal body tumors while twelve had glial tumors, one case of cavernoma.
Obstructive hydrocephalus was treated by CSF diversion before tumor surgery.
Postoperative complications included ataxia, double vision, and Parinaud's
syndrome. CONCLUSION: The merit of the expanded supracerebellar infratentorial
approach is adding a unilateral paramedian expansion to the classical approach.
This paramedian expansion offers a better lateral and inferior tumor resection.
This approach does not add any risk of more postoperative complications or
jeopardizing the neurological state than the classical midline approach. PRACTICE
AND IMPLICATIONS: The paramedian expansion offers a better lateral and inferior
tumor resection and a better view of the contralateral extension within the
posterior third ventricle. Collicular lesions are better controlled using this
approach by gentle inferior and lateral retraction of the cerebellum. The
expanded supracerebellar infratentorial approach allows for working on the
lateral tumor extension without jeopardizing the deep venous system.
PMID- 26426426
TI - Education and Imaging. Gastrointestinal: Sarcomatoid carcinoma of the colon, a
rare and highly aggressive tumor subtype.
PMID- 26426427
TI - Remote Control of the Planar Chirality in Peptide-Bound Metallomacrocycles and
Dynamic-to-Static Planar Chirality Control Triggered by Solvent-Induced 3(10)-to
alpha-Helix Transitions.
AB - The dynamic planar chirality in a peptide-bound Ni(II)-salphen-based macrocycle
can be remotely controlled. First, a right-handed (P)-3(10)-helix is induced in
the dynamic helical oligopeptides by a chiral amino acid residue far from the
macrocyclic framework. The induced planar chirality remains dynamic in chloroform
and acetonitrile, but is almost completely locked in fluoroalcohols as a result
of the solvent-induced transition of the peptide chains from a 3(10)-helix to a
wider alpha-helix, which freezes the rotation of the pendant peptide units around
the macrocycle.
PMID- 26426429
TI - Obesity, low levels of physical activity and smoking present opportunities for
primary care asthma interventions: an analysis of baseline data from The Asthma
Tools Study.
AB - BACKGROUND: Asthma prevalence, severity and outcomes are associated with various
patient characteristics and lifestyle choices. AIMS: To identify potentially
modifiable factors associated with poor asthma outcomes among US primary care
patients. METHODS: Using baseline data from the Asthma Tools Study, we calculated
cross-sectional frequencies of activity levels, smoking, secondhand smoke
exposure and the presence of obesity, as well as rates of out-of-control asthma
and asthma exacerbations. Frequencies were stratified by sex, and into three age
groups: 5-11 years, 12-18 years and 19 years and older. Logistic regression was
used to identify factors associated with each of the asthma outcomes. RESULTS: In
the 901 individuals enrolled in this asthma study, tobacco smoke exposure,
obesity, low activity levels, poverty, inadequately controlled asthma and high
asthma-related health-care utilisation were common. Across all age groups,
obesity was associated with poorer asthma outcomes: either poor asthma control
(odds ratio (OR)=2.3, 95% confidence interval (CI) 1.1-4.7 in 5- to 11-year-olds
and OR=1.5, 95% CI 1.1-2.2 in adults) or asthma exacerbations (OR 2.9, 95% CI 1.6
5.1 in 12- to 18-year-olds and OR 1.7, 95% CI 1.1-2.5 in adults). Among adults,
smoking was associated with both measures of poorer asthma outcomes; inadequate
asthma control (OR=2.3, 95% CI 1.5-3.5), and asthma exacerbations (OR 1.7, 95% CI
1.1-2.6), and low physical activity were associated with poor asthma control
(OR=1.5, 95% CI 1.1-2.2). CONCLUSIONS: Obesity, low levels of physical activity
and smoking are common, and they are associated with poor asthma outcomes in a
sample of primary care patients, suggesting important targets for intervention.
PMID- 26426430
TI - Correlation of Thermal Stability and Structural Distortion of DNA Interstrand
Cross-Links Produced from Oxidized Abasic Sites with Their Selective Formation
and Repair.
AB - C4'-oxidized (C4-AP) and C5'-oxidized abasic sites (DOB) that are produced
following abstraction of a hydrogen atom from the DNA backbone reversibly form
cross-links selectively with dA opposite a 3'-adjacent nucleotide, despite the
comparable proximity of an opposing dA. A previous report on UvrABC incision of
DNA substrates containing stabilized analogues of the ICLs derived from C4-AP and
DOB also indicated that the latter is repaired more readily by nucleotide
excision repair [Ghosh, S., and Greenberg, M. M. (2014) Biochemistry 53, 5958
5965]. The source for selective cross-link formation was probed by comparing the
reactivity of ICL analogues of C4-AP and DOB that mimic the preferred and
disfavored cross-links with that of reagents that indirectly detect distortion by
reacting with the nucleobases. The disfavored C4-AP and DOB analogues were each
more reactive than the corresponding preferred cross-link substrates, suggesting
that the latter are more stable, which is consistent with selective ICL
formation. In addition, the preferred DOB analogue is more reactive than the
respective C4-AP ICL, which is consistent with its more efficient incision by
UvrABC. The conclusions drawn from the chemical probing experiments are
corroborated by UV melting studies. The preferred ICLs exhibit melting
temperatures higher than those of the corresponding disfavored isomers. These
studies suggest that oxidized abasic sites form reversible interstrand cross
links with dA opposite the 3'-adjacent thymidine because these products are more
stable and the thermodynamic preference is reflected in the transition states for
their formation.
PMID- 26426431
TI - Clinicopathological analysis of programmed cell death 1 and programmed cell death
ligand 1 expression in the tumour microenvironments of diffuse large B cell
lymphomas.
AB - AIMS: To investigate the clinicopathological characteristics of programmed cell
death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expression in the
tumour microenvironments of diffuse large B cell lymphoma (DLBCL). METHODS AND
RESULTS: Tumour tissues from 126 DLBCL patients were immunostained for PD-L1 and
PD-1. The expression of PD-L1 by tumour cells and/or tumour-infiltrating immune
cells (mainly macrophages) was evaluated, and the number of tumour-infiltrating
PD-1(+) cells was assessed. PD-L1 expression in tumour cells was observed in
61.1% of DLBCLs, with a weak intensity in 29.4%, moderate intensity in 21.4% and
strong intensity in 10.3% of cases. Strong PD-L1 expression in tumour cells was
associated significantly with the presence of B symptoms (adjusted P = 0.005) and
Epstein-Barr virus (EBV) infection (adjusted P = 0.015), and tended to be higher
in activated B cell-like immunophenotype (16.7%) than germinal centre B cell-like
immunophenotype (2.5%) (adjusted P = 0.271). DLBCLs with PD-L1 expression in
tumour cells/macrophages showed similar clinicopathological characteristics. The
quantity of PD-1(+) tumour-infiltrating lymphocytes correlated positively with
the level of PD-L1 expression in tumour cells (P = 0.042) or in tumour
cells/macrophages (P = 0.03). Increased infiltration of PD-1(+) cells was
associated with prolonged progression-free survival (P = 0.005) and overall
survival (P = 0.026) in DLBCL patients treated with rituximab-cyclophosphamide,
doxorubicin, vincristine, prednisone (R-CHOP), whereas PD-L1 expression had no
prognostic significance. CONCLUSIONS: PD-L1 and PD-1 were expressed variably in
DLBCLs by tumour cells and tumour-infiltrating immune cells and might be
potential therapeutic targets using PD-1/PD-L1 blockade.
PMID- 26426432
TI - Simultaneous mechanical property and biodegradation improvement of wollastonite
bioceramic through magnesium dilute doping.
AB - The large-area bone defects in head (including calvarial, orbital, and
maxillofacial bone) and segmental bone are attracting increased attention in a
wide range of clinical departments. A key requirement for the clinical success of
the bioactive ceramics is the match of the mechanical behavior of the implants
with the specific bone tissue to be filled. This raises the question as to what
design strategy might be the best indicators for the balance between mechanical
properties and biological performances. Here we go beyond the traditional
approaches that use phase conversion or biphasic hybrid; instead, we achieved a
simultaneous enhancement of several mechanical parameters and optimalization of
biodegradability by using a dilute doping of Mg in a single-phase wollastonite
bioceramic. We show that the wollastonite ceramic can be rationally tuned in
phase (alpha or beta), mechanical strength (in compression and bending mode),
elastic modulus (18-23GPa), and fracture toughness (>3.2MPam(1/2)) through the
usage of Mg dopant introduced at precisely defined dilute concentrations (Mg/Ca
molar ratio: 1.2-2.1%). Meanwhile, the dilute Mg-doped wollastonite ceramics are
shown to exhibit good bioactivity in vitro in SBF but biodegradation in Tris is
inversely proportional to Mg content. Consequently, such new highly bioactive
ceramics with appreciable strength and toughness are promising for making
specific porous scaffolds for enhancing large segmental bone defect and thin-wall
bone defect repair.
PMID- 26426433
TI - Gate-Tunable Electron Transport Phenomena in Al-Ge?111?-Al Nanowire
Heterostructures.
AB - Electrostatically tunable negative differential resistance (NDR) is demonstrated
in monolithic metal-semiconductor-metal (Al-Ge-Al) nanowire (NW) heterostructures
integrated in back-gated field-effect transistors (FETs). Unambiguous signatures
of NDR even at room temperature are attributed to intervalley electron transfer.
At yet higher electric fields, impact ionization leads to an exponential increase
of the current in the ?111? oriented Ge NW segments. Modulation of the transfer
rates, manifested as a large tunability of the peak-to-valley ratio (PVR) and the
onset of impact ionization is achieved by the combined influences of
electrostatic gating, geometric confinement, and heterojunction shape on hot
electron transfer and by electron-electron scattering rates that can be altered
by varying the charge carrier concentration in the NW FETs.
PMID- 26426434
TI - Necrotizing Enterocolitis Is Not Associated With Sequence Variants in Antioxidant
Response Genes in Premature Infants.
AB - Reactive oxygen species mediate intestinal injury in necrotizing enterocolitis
(NEC), and yet the contribution of antioxidant response (ARE) gene polymorphisms
to NEC risk remains unknown. Premature infants recruited in a multicenter study
were genotyped for 6 ARE variants. Among 637 infants, 52 had NEC, and 22
developed surgical NEC. Gestational age <28 weeks (P < 0.02) and African American
race (P = 0.03) were associated with NEC. The NFE2L2 (rs6721961), SOD2 (rs4880),
GSTP1 (rs1695), NQO1 (rs1800566), GCLC (rs17883901), and HMOX1 (rs2071747)
variants were not associated with medical or surgical NEC. This study does not
support a role for common deleterious ARE variants in NEC.
PMID- 26426436
TI - Synthesis and strong photooxidation power of a supramolecular hybrid comprising a
polyoxometalate and Ru(II) polypyridyl complex with zinc(II).
AB - A novel method for constructing supramolecular hybrids composed of
polyoxometalates and photofunctional metal complexes was developed. A Ru(II)
complex with phosphonate groups (RuP) strongly interacted with Zn(II) to afford a
2 : 1 trinuclear metal complex ([(RuP)2Zn](3+)). In dimethylsulfoxide,
[(RuP)2Zn](3+) strongly interacted with a Keggin-type heteropolyoxometalate (Si
WPOM) to form a 1 : 1 hybrid ([(RuP)2Zn]-POM). Irradiation of [(RuP)2Zn]-POM in
the presence of diethanolamine caused rapid accumulation of the one-electron
reduced hybrid with a quantum yield of 0.99.
PMID- 26426435
TI - Altered NMDA receptor function in primary cultures of hippocampal neurons from
mice lacking the Homer2 gene.
AB - N-Methyl-D-Aspartate (NMDA) receptors are inhibited during acute exposure to
ethanol and are involved in changes in neuronal plasticity following repeated
ethanol exposure. The postsynaptic scaffolding protein Homer2 can regulate the
cell surface expression of NMDA receptors in vivo, and mice with a null mutation
of the Homer2 gene exhibit an alcohol-avoiding and -intolerant phenotype that is
accompanied by a lack of ethanol-induced glutamate sensitization. Thus, Homer2
deletion may perturb the function or acute ethanol sensitivity of the NMDA
receptor. In this study, the function and ethanol sensitivity of glutamate
receptors in cultured hippocampal neurons from wild-type (WT) and Homer2 knock
out (KO) mice were examined at 7 and 14 days in vitro (DIV) using standard whole
cell voltage-clamp electrophysiology. As compared with wild-type controls, NMDA
receptor current density was reduced in cultured hippocampal neurons from Homer2
KO mice at 14 DIV, but not at 7 DIV. There were no genotype-dependent changes in
whole-cell capacitance or in currents evoked by kainic acid. The GluN2B-selective
antagonist ifenprodil inhibited NMDA-evoked currents to a similar extent in both
wild-type and Homer2 KO neurons and inhibition was greater at 7 versus 14 DIV.
NMDA receptor currents from both WT and KO mice were inhibited by ethanol (10-100
mM) and the degree of inhibition did not differ as a function of genotype. In
conclusion, NMDA receptor function, but not ethanol sensitivity, is reduced in
hippocampal neurons lacking the Homer2 gene.
PMID- 26426439
TI - Mg-Zr Cosubstituted Ta3N5 Photoanode for Lower-Onset-Potential Solar-Driven
Photoelectrochemical Water Splitting.
AB - In p/n photoelectrochemical (PEC) cell systems, a low onset potential for the
photoanode, as well as a high photocurrent, are critical for efficient water
splitting. Here, we report a Mg-Zr cosubstituted Ta3N5 (Ta3N5:Mg+Zr) photoanode,
designed to provide a more negative onset potential for PEC water splitting. The
anodic photocurrent onset on Ta3N5:Mg+Zr was 0.55 V(RHE) under AM 1.5G-simulated
sunlight, which represented a negative shift from the ca. 0.8 V(RHE) for pure
Ta3N5. This negative shift in the onset potential of PEC water splitting was
attributed to the change in the bandgap potential due to partial substitution by
the foreign ions Mg(2+) and/or Zr(4+).
PMID- 26426440
TI - Small RNA and Degradome Sequencing Reveal Complex Roles of miRNAs and Their
Targets in Developing Wheat Grains.
AB - Plant microRNAs (miRNAs) have been shown to play critical roles in plant
development. In this study, we employed small RNA combined with degradome
sequencing to survey development-related miRNAs and their validated targets
during wheat grain development. A total of 186 known miRNAs and 37 novel miRNAs
were identified in four small RNA libraries. Moreover, a miRNA-like long hairpin
locus was first identified to produce 21~22-nt phased siRNAs that act in trans to
cleave target mRNAs. A comparison of the miRNAomes revealed that 55 miRNA
families were differentially expressed during the grain development. Predicted
and validated targets of these development-related miRNAs are involved in
different cellular responses and metabolic processes including cell
proliferation, auxin signaling, nutrient metabolism and gene expression. This
study provides insight into the complex roles of miRNAs and their targets in
regulating wheat grain development.
PMID- 26426441
TI - Vitamin D deficiency is an independent risk factor for PTDM after kidney
transplantation.
AB - An association between 25 hydroxyvitamin D [25(OH)D] deficiency and type 2
diabetes was observed in the general population. Such association was not
investigated in kidney transplant recipients. We prospectively evaluated 444
patients following primary kidney transplantation between 2000 and 2010. The
25(OH)D level at transplantation was classified into three grades: deficiency (<
10 ng/ml), insufficiency (>= 10 and < 30 ng/ml), and normal range (>= 30 ng/ml).
Time to Post-Transplant Diabetes Mellitus (PTDM) was defined according to the day
of first prescription of hypoglycemic treatment. The 25(OH)D level at
transplantation was deficient in 88 patients, insufficient in 264 patients, and
normal in 92 patients. At 1 year post-transplantation, cumulative incidence of
PTDM was 13.2%. Cox multivariate analysis indicated that 25(OH)D deficiency (<=
10 ng/ml) at the time of transplantation was an independent risk factor for PTDM
within the first year post-transplantation (HR = 2.41, 95% CI 1.01-5.75, P =
0.048), whereas insufficiency tended to increase this risk, although not
significantly. 25(OH)D deficiency is a new independent risk factor for PTDM
within the first year after kidney transplantation. Our study suggests that
25(OH)D may be a marker of general health in kidney transplant recipients and
could alert clinicians for PTDM risk.
PMID- 26426442
TI - Management of aripiprazole-induced tardive Pisa syndrome: a case report and
literature review.
AB - Pisa syndrome (PS) is characterized by an abnormally sustained posture with
flexion of the body and head to one side and slight axial rotation of the trunk.
PS has been related to the use of neuroleptics and is clinically classified as
either an acute or a tardive dystonia. This is the first report describing a case
of late-onset PS, occurring in a young patient treated with aripiprazole for 2
years. To establish optimal treatment management, we reviewed the literature on
aripiprazole-induced PS and tardive dystonia. In light of current knowledge, we
proposed a multistep algorithm to aid in the clinical management of this
condition.
PMID- 26426443
TI - Use of benzodiazepines in obsessive-compulsive disorder.
AB - This study aimed to determine the frequency of benzodiazepine (BDZ) use in a
large sample of patients with obsessive-compulsive disorder (OCD) and ascertain
the type of BDZ used and the correlates and predictors of BDZ use in OCD. The
sample consisted of 955 patients with OCD from a comprehensive, cross-sectional,
multicentre study conducted by the Brazilian Research Consortium on Obsessive
Compulsive Spectrum Disorders between 2003 and 2009. The rate of BDZ use over
time in this OCD sample was 38.4%. Of individuals taking BDZs, 96.7% used them in
combination with other medications, usually serotonin reuptake inhibitors. The
most commonly used BDZ was clonazepam. Current age, current level of anxiety and
number of additional medications for OCD taken over time significantly predicted
BDZ use. This is the first study to comprehensively examine BDZ use in OCD
patients, demonstrating that it is relatively common, despite recommendations
from treatment guidelines. Use of BDZs in combination with several other
medications over time and in patients with marked anxiety suggests that OCD
patients taking BDZs may be more complex and more difficult to manage. This calls
for further research and clarification of the role of BDZs in the treatment of
OCD.
PMID- 26426450
TI - Do resonance-assisted intramolecular halogen bonds exist without a charge
transfer and a sigma-hole?
AB - To analyze the properties and mechanisms of six types of intramolecular resonance
assisted halogen bonds (Br...O, Cl...O, F...O, Br...O, Cl...S and F...S), we have
chosen the five-membered closed ring system X-C1R1=C3R2-C2R3=Y (X = Br, Cl & F; Y
= O & S) of unsaturated compounds with the substituents NO2, CH3 and H. A total
of 78 structures were investigated by quantum chemical calculations at the
MP2/aug-cc-pVTZ level of theory. A molecular electrostatic potential (MESP) map
reveals that the cusp point of the sigma-hole was not utilized but the belt point
was used for all these intramolecular halogen-bonding interactions, indicating
that all are electrostatic interactions. The halogen-bonding angle is below 100
degrees with the strongest interactions. The value of the nucleus-independent
chemical shift (NICS (1)) reflects the changes and efficiency of resonance in all
structures with a long bond. The presence of all interactions was proved by the
bond critical point (BCP) and analyzed through its electron density, Laplacian of
electron density and ellipticity parameter. The linear-probability correlation
between the difference of the sum of the van der Waals radius and the non
covalent bond length (?vdW-L) and the electron density of the BCP was reported.
2D and 3D-NCI (non covalent interactions) plots show that halogen-bonding
interactions are a mixed type of interactions with an attractive term. Natural
bond orbital (NBO) analysis clearly indicates that the halogen bond lacks charge
transfer and orbital overlapping through non-interacting lobes.
PMID- 26426444
TI - Cloning and Characterization of 5' Flanking Regulatory Sequences of AhLEC1B Gene
from Arachis Hypogaea L.
AB - LEAFY COTYLEDON1 (LEC1) is a B subunit of Nuclear Factor Y (NF-YB) transcription
factor that mainly accumulates during embryo development. We cloned the 5'
flanking regulatory sequence of AhLEC1B gene, a homolog of Arabidopsis LEC1, and
analyzed its regulatory elements using online software. To identify the crucial
regulatory region, we generated a series of GUS expression frameworks driven by
different length promoters with 5' terminal and/or 3' terminal deletion. We
further characterized the GUS expression patterns in the transgenic Arabidopsis
lines. Our results show that both the 65 bp proximal promoter region and the 52
bp 5' UTR of AhLEC1B contain the key motifs required for the essential promoting
activity. Moreover, AhLEC1B is preferentially expressed in the embryo and is co
regulated by binding of its upstream genes with both positive and negative
corresponding cis-regulatory elements.
PMID- 26426451
TI - Does attention redirection contribute to the effectiveness of attention bias
modification on social anxiety?
AB - Attention bias modification (ABM) is designed to modify threat-related attention
bias and thus alleviate anxiety. The current research examined whether
consistently directing attention towards targeted goals per se contributes to ABM
efficacy. We randomly assigned 68 non-clinical college students with elevated
social anxiety to non-valence-specific attend-to-geometrics (AGC), attention
modification (AMC), or attention control (ACC) conditions. We assessed
subjective, behavioral, and physiological reactivity to a speech task and self
reported social anxiety symptoms. After training, participants in the AMC
exhibited an attention avoidance from threat, and those in the AGC responded more
rapidly toward targeted geometrics. There was a significant pre- to post
reduction in subjective speech distress across groups, but behavioral and
physiological reactivity to speech, as well as self-report social anxiety
symptoms, remained unchanged. These results lead to questions concerning
effectiveness of ABM training for reducing social anxiety. Further examination of
the current ABM protocol is required.
PMID- 26426449
TI - Triptolide enhances the tumoricidal activity of TRAIL against renal cell
carcinoma.
AB - Renal cell carcinoma (RCC) is resistant to traditional cancer therapies, and
metastatic RCC (mRCC) is incurable. The shortcomings in current therapeutic
options for patients with mRCC provide the rationale for the development of novel
treatment protocols. Tumor necrosis factor-related apoptosis-inducing ligand
(TRAIL) has proven to be a potent inducer of tumor cell death in vitro and in
vivo, and a number of TRAIL death receptor agonists (recombinant TRAIL or TRAIL
death receptor-specific mAb) have been developed and tested clinically.
Unfortunately the clinical efficacy of TRAIL has been underwhelming and is likely
due to a number of possible mechanisms that render tumors resistant to TRAIL,
prompting the search for drugs that increase tumor cell susceptibility to TRAIL.
The objective of this study was to determine the effectiveness of combining the
diterpene triepoxide triptolide, or its water-soluble prodrug, Minnelide, with
TRAIL receptor agonists against RCC in vitro or in vivo, respectively. TRAIL
induced apoptotic death of human RCC cells was increased in the presence of
triptolide. The triptolide-induced sensitization was accompanied by increased
TRAIL-R2 (DR5) and decreased heat shock protein 70 expression. In vivo treatment
of mice bearing orthotopic RCC (Renca) tumors showed the combination of Minnelide
and agonistic anti-DR5 mAb significantly decreased tumor burden and increased
animal survival compared to either therapy alone. Our data suggest
triptolide/Minnelide sensitizes RCC cells to TRAIL-induced apoptosis through
altered TRAIL death receptor and heat shock protein expression.
PMID- 26426452
TI - Adipokinins in pregnancies at risk of preterm delivery.
AB - OBJECTIVE: To compare adipokinins between women experiencing preterm labor (PTL)
and prior preterm deliveries (PTD). STUDY DESIGN: In this prospective
observational cohort, 110 women with a singleton <35 weeks at increased risk of
PTD were studied. Serum leptin, adiponectin, and resistin were obtained at three
times (23-34 weeks, 35-36 weeks, at delivery) and analyzed via enzyme-linked
immunosorbent assay. The adipokinins were compared across time and between PTL (n
= 59) and prior PTD (n = 51) groups using generalized estimated equation models.
RESULTS: There were no differences in leptin, adiponectin, or resistin levels
over the three times between the PTL and PTD groups. There was a trend toward
higher leptin levels (p = 0.06 unadjusted analysis, p = 0.09 adjusted analysis)
at 23-34 weeks. When stratified by body mass index (BMI), there were differences
in leptin (p < 0.001 for BMI < 30; p = 0.77 for BMI >= 30) and adiponectin (p =
0.04 for BMI < 30; p = 0.09 for BMI >= 30), but not in resistin over the three
times between the PTL and prior PTD groups. CONCLUSION: There were no significant
differences in adipokinins in women with PTL and a prior PTD. The trends toward
higher leptin levels at 23-34 weeks in women with PTL may represent a
compensatory response and require further evaluation in the study of treatments
for PTL.
PMID- 26426453
TI - MASCG: Multi-Atlas Segmentation Constrained Graph method for accurate
segmentation of hip CT images.
AB - This paper addresses the issue of fully automatic segmentation of a hip CT image
with the goal to preserve the joint structure for clinical applications in hip
disease diagnosis and treatment. For this purpose, we propose a Multi-Atlas
Segmentation Constrained Graph (MASCG) method. The MASCG method uses multi-atlas
based mesh fusion results to initialize a bone sheetness based multi-label graph
cut for an accurate hip CT segmentation which has the inherent advantage of
automatic separation of the pelvic region from the bilateral proximal femoral
regions. We then introduce a graph cut constrained graph search algorithm to
further improve the segmentation accuracy around the bilateral hip joint regions.
Taking manual segmentation as the ground truth, we evaluated the present approach
on 30 hip CT images (60 hips) with a 15-fold cross validation. When the present
approach was compared to manual segmentation, an average surface distance error
of 0.30 mm, 0.29 mm, and 0.30 mm was found for the pelvis, the left proximal
femur, and the right proximal femur, respectively. A further look at the
bilateral hip joint regions demonstrated an average surface distance error of
0.16 mm, 0.21 mm and 0.20 mm for the acetabulum, the left femoral head, and the
right femoral head, respectively.
PMID- 26426454
TI - Further Examination of the Resetting Zone in Supraventricular Tachycardia.
PMID- 26426455
TI - Development of chitosan/poly-gamma-glutamic acid/pluronic/curcumin nanoparticles
in chitosan dressings for wound regeneration.
AB - The hydrophobic polyphenol curcumin has anti-inflammatory, antimicrobial, and
wound-healing properties that warrant its pharmacological consideration. We
report a curcumin nanoparticle with a tripolymeric composite that can be used as
a delivery device for wound healing. The present composite nanoparticles were
prepared with three biocompatible polymers of chitosan, poly-gamma-glutamic acid,
and pluronic using a simple ionic gelation technology. Pluronic was used to
enhance the solubility of curcumin in chitosan/poly-gamma-glutamic acid
nanoparticles, leading to the incorporation of chitosan/poly-gamma-glutamic
acid/pluronic/curcumin nanoparticles into chitosan membranes, and reduced
inflammation and bacterial infection during wound regeneration. Nanoparticles
were of 193.1 +/- 8.9 nm and had a zeta potential of 20.6 +/- 2.4 mV. Moreover,
in vitro analyses indicated controlled curcumin release in a simulated skin
tissue model. Subsequent in vivo studies show that chitosan wound dressing
containing chitosan/poly-gamma-glutamic acid/pluronic/curcumin nanoparticles
promoted neocollagen regeneration and tissue reconstruction. (c) 2015 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 81-90, 2017.
PMID- 26426456
TI - The role of serological titres in the diagnosis of ocular toxoplasmosis.
PMID- 26426457
TI - Brief report: Assessing youth well-being in global emergency settings: Early
results from the Emergency Developmental Assets Profile.
AB - The 13-item Emergency Developmental Assets Profile measures the well-being of
children and youth in emergency settings such as refugee camps and armed conflict
zones, assessing whether young people are experiencing adequate positive
relationships and opportunities, and developing positive values, skills, and self
perceptions, despite being in crisis circumstances. The instrument was found to
have acceptable and nearly identical internal consistency reliability in 22
administrations in non-emergency samples in 15 countries (.75), and in 4 samples
of youth ages 10-18 (n = 1550) in the emergency settings (war refugees and
typhoon victims, .74) that are the measure's focus, and evidence of convergent
validity. Confirmatory Factor Analysis showed acceptable model fit among those
youth in emergency settings. Measures of model fit showed that the Em-DAP has
configural and metric invariance across all emergency contexts and scalar
invariance across some. The Em-DAP is a promising brief cross-cultural tool for
assessing the developmental quality of life as reported by samples of youth in a
current humanitarian crisis situation. The results can help to inform
international relief program decisions about services and activities to be
provided for children, youth, and families in emergency settings.
PMID- 26426459
TI - Multidetector computed tomography angiography in the management of transarterial
embolization of primary and secondary liver malignancy.
AB - BACKGROUND: Endovascular management is the mainstay of therapy for most patients
with primary and secondary liver tumors. Radiologist should understand the
anatomy of the hepatic vasculature and tumor feeding vessels to ensure successful
conduction of the embolization procedure. The aim of this study was to evaluate
the accuracy of multidetector computed tomographic angiography (MDCTA) for the
evaluation of hepatic arterial anatomy and tumor feeding vessels prior to
embolization procedure. METHODS: This study included 42 patients. They were 30
with hepatocellular carcinoma, 6 with colorectal cancer metastases, 3 with
intrahepatic cholangiocellular carcinoma, 2 with giant focal nodular hyperplasia
and 1 with gallbladder tumor. The findings of MDCTA were compared with the DSA
findings, which served as the standard of reference. Sensitivity and specificity
of the MDCTA were calculated. RESULTS: MDCTA showed 100% coincidence with the DSA
and 100% accuracy in the evaluation of gross hepatic arterial anatomy and its
variations. 61 out of the 64 feeders were correctly identified with the MDCTA.
False positives and false negatives were 3 each. Accordingly sensitivity and
specificity were 95.31%, 97.95% respectively. CONCLUSIONS: MDCT angiography
permits accurate assessment of the hepatic vascular anatomy. Although some
pathways of tumor irrigation may not be well visible on the computed tomography.
These require detailed reevaluation of suspected tumor feeders during
embolization procedure.
PMID- 26426458
TI - Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the
Critically Ill.
AB - RATIONALE: Hypoxemia is common during endotracheal intubation of critically ill
patients and may predispose to cardiac arrest and death. Administration of
supplemental oxygen during laryngoscopy (apneic oxygenation) may prevent
hypoxemia. OBJECTIVES: To determine if apneic oxygenation increases the lowest
arterial oxygen saturation experienced by patients undergoing endotracheal
intubation in the intensive care unit. METHODS: This was a randomized, open
label, pragmatic trial in which 150 adults undergoing endotracheal intubation in
a medical intensive care unit were randomized to receive 15 L/min of 100% oxygen
via high-flow nasal cannula during laryngoscopy (apneic oxygenation) or no
supplemental oxygen during laryngoscopy (usual care). The primary outcome was
lowest arterial oxygen saturation between induction and 2 minutes after
completion of endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: Median
lowest arterial oxygen saturation was 92% with apneic oxygenation versus 90% with
usual care (95% confidence interval for the difference, -1.6 to 7.4%; P = 0.16).
There was no difference between apneic oxygenation and usual care in incidence of
oxygen saturation less than 90% (44.7 vs. 47.2%; P = 0.87), oxygen saturation
less than 80% (15.8 vs. 25.0%; P = 0.22), or decrease in oxygen saturation
greater than 3% (53.9 vs. 55.6%; P = 0.87). Duration of mechanical ventilation,
intensive care unit length of stay, and in-hospital mortality were similar
between study groups. CONCLUSIONS: Apneic oxygenation does not seem to increase
lowest arterial oxygen saturation during endotracheal intubation of critically
ill patients compared with usual care. These findings do not support routine use
of apneic oxygenation during endotracheal intubation of critically ill adults.
Clinical trial registered with www.clinicaltrials.gov (NCT 02051816).
PMID- 26426460
TI - Irritable bowel syndrome in quiescent inflammatory bowel disease: a review.
AB - Ongoing troublesome bowel symptoms despite quiescent inflammatory disease are a
frequent management challenge when caring for patients with inflammatory bowel
disease (IBD). Even when active disease has been excluded the prevalence of
residual gastrointestinal symptoms is surprisingly high and the cause often
obscure. The presence of a concurrent functional disorder such as irritable bowel
syndrome (IBS) is associated with worse quality of life, worse physical
functioning, higher prevalence of anxiety and greater health care utilization.
Potential etiological mechanisms leading to the development of IBS like symptoms
include the development of visceral hypersensitivity following the original
inflammatory insult, alteration in cortical processing, dysbiosis and residual
subacute inflammation. Therapeutic options for managing IBS in patients with IBD
include dietary modification, interventions targeted at correction of visceral
sensory dysfunction or cortical processing and modulation of the gut microbiota.
As there are few studies specifically examining the treatment of IBS in patients
with IBD, the majority of therapeutic interventions are extrapolated from the IBS
literature. Given the frequency of residual functional symptoms in IBS,
significantly more research is warranted in this field.
PMID- 26426461
TI - Cerebral Blood-Flow Regulation During Hemorrhage.
AB - Massive uncontrolled blood loss can occur under a variety of conditions including
trauma, as a complication of childbirth or surgery, ruptured ulcers, clotting
disorders, and hemorrhagic fevers. Across the continuum of hemorrhage, loss of
blood volume is a significant challenge to the maintenance of cerebral perfusion.
During the initial stages of hemorrhage, reflex mechanisms are activated to
protect cerebral perfusion, but persistent blood loss will eventually reduce
global cerebral blood flow and the delivery of metabolic substrates, leading to
generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death.
Cerebral blood flow is controlled by various regulatory mechanisms, including
prevailing arterial pressure, intracranial pressure, arterial blood gases, neural
activity, and metabolic demand. Hemorrhage represents a unique physiological
stress to the brain, as it influences each of these regulatory mechanisms,
resulting in complex interplay that ultimately challenges the ability of the
brain to maintain adequate perfusion. Early studies of actual hemorrhage in
humans employed blood loss protocols up to 1000 mL, but did not include any
measurements of cerebral blood flow. As ethical considerations necessarily
constrain the use of human volunteers for massive blood loss studies that induce
irreversible shock, most of what is known about cerebral blood-flow responses to
hemorrhage has been determined from animal models. Limitations of species
differences regarding regulatory mechanisms, anatomy, and the effect of
anesthesia, however, must be considered. Advances in monitoring technologies, and
a recent renewed interest in understanding cerebral blood-flow regulation in
humans, however, is rapidly accelerating knowledge in this field.
PMID- 26426463
TI - Gene Targeting in Neuroendocrinology.
AB - Research in neuroendocrinology faces particular challenges due to the complex
interactions between cells in the hypothalamus, in the pituitary gland and in
peripheral tissues. Within the hypothalamus alone, attempting to target a
specific neuronal cell type can be problematic due to the heterogeneous nature
and level of cellular diversity of hypothalamic nuclei. Because of the inherent
complexity of the reproductive axis, the use of animal models and in vivo
experiments are often a prerequisite in reproductive neuroendocrinology. The
advent of targeted genetic modifications, particularly in mice, has opened new
avenues of neuroendocrine research. Within this review, we evaluate various mouse
models used in reproductive neuroendocrinology and discuss the different
approaches to generate genetically modified mice, along with their inherent
advantages and disadvantages. We also discuss a variety of versatile genetic
tools with a focus on their potential use in reproductive neuroendocrinology.
PMID- 26426464
TI - Metabolism at the Max: How Vertebrate Organisms Respond to Physical Activity.
AB - Activity metabolism is supported by phosphorylated reserves (adenosine
triphosphate, creatine phosphate), glycolytic, and aerobic metabolism. Because
there is no apparent variation between vertebrate groups in phosphorylated
reserves or glycolytic potential of skeletal muscle, variation in maximal
metabolic rate between major vertebrate groups represents selection operating on
aerobic mechanisms. Maximal rates of oxygen consumption in vertebrates are
supported by increased conductive and diffusive fluxes of oxygen from the
environment to the mitochondria. Maximal CO2 efflux from the mitochondria to the
environment must be matched to oxygen flux, or imbalances in pH will occur. Among
vertebrates, there are a variety of modes of locomotion and vastly different
rates of metabolism supported by a variety of cardiorespiratory architectures.
However, interclass comparisons strongly implicate systemic oxygen transport as
the rate-limiting step to maximal oxygen consumption for all vertebrate groups.
The key evolutionary step that accounts for the approximately 10-fold increase in
maximal oxygen flux in endotherms versus ectotherms appears to be maximal heart
rate. Other variables such as ventilation, pulmonary/gill, and tissue diffusing
capacity, have excess capacity and thus are not limiting to maximal oxygen
consumption. During maximal activity, the ratio of ventilation to respiratory
system blood flow is remarkably similar among vertebrates, and CO2 extraction
efficiency increases while oxygen extraction efficiency decreases, suggesting
that the respiratory system provides the largest resistance to maximal CO2 flux.
Despite the large variation in modes of activity and rates of metabolism, maximal
rates of oxygen and CO2 flux appear to be limited by the cardiovascular and
respiratory systems, respectively.
PMID- 26426465
TI - Human Physiology in an Aquatic Environment.
AB - Water covers over 70% of the earth, has varying depths and temperatures and
contains much of the earth's resources. Head-out water immersion (HOWI) or
submersion at various depths (diving) in water of thermoneutral (TN) temperature
elicits profound cardiorespiratory, endocrine, and renal responses. The
translocation of blood into the thorax and elevation of plasma volume by
autotransfusion of fluid from cells to the vascular compartment lead to increased
cardiac stroke volume and output and there is a hyperperfusion of some tissues.
Pulmonary artery and capillary hydrostatic pressures increase causing a decline
in vital capacity with the potential for pulmonary edema. Atrial stretch and
increased arterial pressure cause reflex autonomic responses which result in
endocrine changes that return plasma volume and arterial pressure to preimmersion
levels. Plasma volume is regulated via a reflex diuresis and natriuresis.
Hydrostatic pressure also leads to elastic loading of the chest, increasing work
of breathing, energy cost, and thus blood flow to respiratory muscles. Decreases
in water temperature in HOWI do not affect the cardiac output compared to TN;
however, they influence heart rate and the distribution of muscle and fat blood
flow. The reduced muscle blood flow results in a reduced maximal oxygen
consumption. The properties of water determine the mechanical load and the
physiological responses during exercise in water (e.g. swimming and water based
activities). Increased hydrostatic pressure caused by submersion does not affect
stroke volume; however, progressive bradycardia decreases cardiac output. During
submersion, compressed gas must be breathed which introduces the potential for
oxygen toxicity, narcosis due to nitrogen, and tissue and vascular gas bubbles
during decompression and after may cause pain in joints and the nervous system.
PMID- 26426466
TI - Aging Effects on Cardiac Progenitor Cell Physiology.
AB - Cardiac aging has been confounded by the concept that the heart is a postmitotic
organ characterized by a predetermined number of myocytes, which is established
at birth and largely preserved throughout life until death of the organ and
organism. Based on this premise, the age of cardiac cells should coincide with
that of the organism; at any given time, the heart would be composed of a
homogeneous population of myocytes of identical age. The discovery that stem
cells reside in the heart and generate cardiac cell lineages has imposed a
reconsideration of the mechanisms implicated in the manifestations of the aging
myopathy. The progressive alterations of terminally differentiated myocytes, and
vascular smooth muscle cells and endothelial cells may represent an epiphenomenon
dictated by aging effects on cardiac progenitor cells (CPCs). Changes in the
properties of CPCs with time may involve loss of self-renewing capacity,
increased symmetric division with formation of daughter committed cells, partial
depletion of the primitive pool, biased differentiation to the fibroblast fate,
impaired ability to migrate, and forced entry into an irreversible quiescent
state. Telomere shortening is a major variable of cellular senescence and organ
aging, and support the notion that CPCs with critically shortened or
dysfunctional telomeres contribute to myocardial aging and chronic heart failure.
These defects constitute the critical variables that define the aging myopathy in
humans. Importantly, a compartment of functionally competent human CPCs persists
in the decompensated heart pointing to stem cell therapy as a novel form of
treatment for the aging myopathy.
PMID- 26426467
TI - Liver Sinusoidal Endothelial Cells.
AB - The liver sinusoidal endothelial cell (LSEC) forms the fenestrated wall of the
hepatic sinusoid and functions as a control post regulating and surveying the
trafficking of molecules and cells between the liver parenchyma and the blood.
The cell acts as a scavenger cell responsible for removal of potential dangerous
macromolecules from blood, and is increasingly acknowledged as an important
player in liver immunity. This review provides an update of the major functions
of the LSEC, including its role in plasma ultrafiltration and regulation of the
hepatic microcirculation, scavenger functions, immune functions, and role in
liver aging, as well as issues that are either undercommunicated or confusingly
dealt with in the literature. These include metabolic functions, including energy
metabolic interplay between the LSEC and the hepatocyte, and adequate ways of
identifying and distinguishing the cells.
PMID- 26426462
TI - Biomechanics of Cardiac Function.
AB - The heart pumps blood to maintain circulation and ensure the delivery of
oxygenated blood to all the organs of the body. Mechanics play a critical role in
governing and regulating heart function under both normal and pathological
conditions. Biological processes and mechanical stress are coupled together in
regulating myocyte function and extracellular matrix structure thus controlling
heart function. Here, we offer a brief introduction to the biomechanics of left
ventricular function and then summarize recent progress in the study of the
effects of mechanical stress on ventricular wall remodeling and cardiac function
as well as the effects of wall mechanical properties on cardiac function in
normal and dysfunctional hearts. Various mechanical models to determine wall
stress and cardiac function in normal and diseased hearts with both systolic and
diastolic dysfunction are discussed. The results of these studies have enhanced
our understanding of the biomechanical mechanism in the development and
remodeling of normal and dysfunctional hearts. Biomechanics provide a tool to
understand the mechanism of left ventricular remodeling in diastolic and systolic
dysfunction and guidance in designing and developing new treatments.
PMID- 26426468
TI - Glucose Homeostasis and Cardiovascular Alterations in Diabetes.
AB - Diabetes mellitus is an increasingly prevalent disease associated with a high
morbidity and mortality burden. Many of the adverse outcomes secondary to
diabetes occur as a result of the impaired glucose homeostasis and
pathophysiological alterations to the cardiovascular system. The purpose of this
overview is to broadly discuss many of the changes that occur in the context of
diabetes that affect cardiovascular function. Following a brief introduction to
the classification and etiologies of the various forms of diabetes, the
mechanisms of impaired glucose homeostasis will be covered. Vascular endothelial
dysfunction, which has been posited to play a major role in the development of
target organ pathology, will be addressed, followed by a discussion of the
effects of diabetes on the renal, cardiovascular, and pulmonary systems.
PMID- 26426469
TI - Pathophysiology of Myocardial Infarction.
AB - Myocardial infarction is defined as sudden ischemic death of myocardial tissue.
In the clinical context, myocardial infarction is usually due to thrombotic
occlusion of a coronary vessel caused by rupture of a vulnerable plaque. Ischemia
induces profound metabolic and ionic perturbations in the affected myocardium and
causes rapid depression of systolic function. Prolonged myocardial ischemia
activates a "wavefront" of cardiomyocyte death that extends from the
subendocardium to the subepicardium. Mitochondrial alterations are prominently
involved in apoptosis and necrosis of cardiomyocytes in the infarcted heart. The
adult mammalian heart has negligible regenerative capacity, thus the infarcted
myocardium heals through formation of a scar. Infarct healing is dependent on an
inflammatory cascade, triggered by alarmins released by dying cells. Clearance of
dead cells and matrix debris by infiltrating phagocytes activates anti
inflammatory pathways leading to suppression of cytokine and chemokine signaling.
Activation of the renin-angiotensin-aldosterone system and release of
transforming growth factor-beta induce conversion of fibroblasts into
myofibroblasts, promoting deposition of extracellular matrix proteins. Infarct
healing is intertwined with geometric remodeling of the chamber, characterized by
dilation, hypertrophy of viable segments, and progressive dysfunction. This
review manuscript describes the molecular signals and cellular effectors
implicated in injury, repair, and remodeling of the infarcted heart, the
mechanistic basis of the most common complications associated with myocardial
infarction, and the pathophysiologic effects of established treatment strategies.
Moreover, we discuss the implications of pathophysiological insights in design
and implementation of new promising therapeutic approaches for patients with
myocardial infarction.
PMID- 26426471
TI - Assessment of Cardiac Function--Basic Principles and Approaches.
AB - Increased access and ability to visualize the heart has provided a means to
measure a myriad of cardiovascular parameters in real or near real time. However,
without fundamental knowledge regarding the basis for cardiac contraction and how
to evaluate cardiac function in terms of loading conditions and inotropic state,
appropriate interpretation of these cardiovascular parameters can be difficult
and can lead to misleading conclusions regarding the functional state of the
cardiac muscle. Thus, in this series of Comprehensive Physiology, the basic
properties of cardiac muscle function, the cardiac cycle, and determinants of
pump function will be reviewed. These basic concepts will then be integrated by
presenting approaches in which the effects of preload, afterload, and myocardial
contractility can be examined. Moreover, the utility of the pressure-volume
relation in terms of assessing both myocardial contractility as well as critical
aspects of diastolic performance will be presented. Finally, a generalized
approach for the assessment and interpretation of cardiac function within the
intact cardiovascular system will be presented.
PMID- 26426472
TI - Skeletal Muscle Changes in Chronic Cardiac Disease and Failure.
AB - Peak exercise performance in healthy man is limited not only by pulmonary or
skeletal muscle function but also by cardiac function. Thus, abnormalities in
cardiac function will have a major impact on exercise performance. Many cardiac
diseases affect exercise performance and indeed for some cardiac conditions such
as atherosclerotic heart disease, exercise testing is frequently used not only to
measure functional capacity but also to make a diagnosis of heart disease,
evaluate the efficacy of treatment, and predict prognosis. Early in the course of
cardiac diseases, exercise performance will be minimally affected but with
disease progression impairment in exercise capacity will become apparent.
Ejection fraction, that is, the percent of blood volume ejected with each cardiac
cycle is often used as a measure of cardiac performance but frequently there is a
dissociation between the ejection fraction and exercise capacity in patients with
heart disease. How abnormalities in cardiac function impacts the muscles,
vasculature, and lungs to impact exercise performance will here be reviewed. The
focus of this work will be on patients with systolic heart failure as the
incidence and prevalence of heart failure is reaching epidemic proportions and
heart failure is the end result of many other chronic cardiac diseases. The
prognostic role of exercise and benefits of exercise training will also be
discussed.
PMID- 26426473
TI - Corrigendum.
PMID- 26426474
TI - An efficient transformation of furano-hydroxychalcones to furanoflavones via base
mediated intramolecular tandem O-arylation and C-O bond cleavage: a new approach
for the synthesis of furanoflavones.
AB - A new and efficient potassium carbonate mediated intramolecular tandem O
arylation followed by C-O bond cleavage of furano-hydroxychalcones is described.
The treatment of furano-hydroxychalcones pongamol (1a) and ovalitenone (2a) with
potassium carbonate in DMF led to the direct formation of the furanoflavones
lanceolatin B (3ab) and pongaglabrone (4ab) in excellent yields. This is the
first report on the cyclization of furano-hydroxychalcones via C-O bond cleavage
(demethoxylation) to produce furanoflavonoids.
PMID- 26426475
TI - Origins of the Stereoselectivity in a Thiourea-Primary Amine-Catalyzed Nazarov
Cyclization.
AB - The origins of stereoselectivity of the Nazarov reactions of alpha
hydroxydivinylketones catalyzed by a vicinal thiourea-primary amine first
reported by Tius have been explored with density functional theory. The
electrocyclization transition structures in which the thiourea group of the
catalyst donates two hydrogen bonds to the keto carbonyl group of the Nazarov
reactant and the primary amine accepts a hydrogen bond from the hydroxyl group of
the reactant have been modeled. The enantiomeric Nazarov transition structures,
which are conventionally described by the absolute sense of conrotation of the
dienone termini ("clockwise" or "counterclockwise") in the literature, are
nonplanar and adopt helically chiral conformations. The interactions of these
helical electrocyclization transition structures with the chiral catalyst are
studied in detail. The organocatalyst is found to employ a combination of
hydrogen bonding and steric effects to achieve helical recognition of the Nazarov
transition state.
PMID- 26426476
TI - Consideration of Submandibular (Undescended) Ectopic Parathyroid Glands in
Surgery and Localization Studies.
PMID- 26426477
TI - Water-like Anomalies and Phase Behavior of a Pair Potential that Stabilizes
Diamond.
AB - Water, silicon, silica, and other liquids that favor tetrahedral order display
thermodynamic, dynamic, and structural anomalies in the pressure range in which
they form tetrahedrally coordinated crystals. The tetrahedral order in these
liquids is induced by anisotropic hydrogen bonding or covalent interactions, or,
in ionic melts, by an appropriate size ratio of the ions. Simple isotropic two
length scale models have been extensively used to understand the origin of
anomalies in complex liquids. However, single-component isotropic liquids
characterized to date generally do not stabilize tetrahedral crystals, and in the
few cases that they do, it was found that the liquids do not display anomalies in
the region of the tetrahedral crystal. This poses the question of whether it is
possible for isotropic pair potentials to display water-like phase behavior and
anomalies. In this work, we use molecular dynamics simulations to investigate the
phase behavior and the existence and loci of anomalies of a single-component
purely repulsive isotropic pair potential that stabilizes diamond in the ground
state over a wide range of pressures. We demonstrate that, akin to water, silica,
and silicon, the isotropic potential of Marcotte, Stillinger, and Torquato (MST)
presents structural, dynamic, and thermodynamic anomalies in the region of
stability of the tetrahedral crystal. The regions of anomalies of MST are nested
in the T-p plane following the same hierarchy as in silica: the region of
diffusional anomalies encloses the region of structural anomalies, which in turn
contains the region of thermodynamic anomalies. To our knowledge, MST is the
first example of pair potential for which water-like anomalies are associated
with the formation of tetrahedral order.
PMID- 26426470
TI - Physiological Implications of Myocardial Scar Structure.
AB - Once myocardium dies during a heart attack, it is replaced by scar tissue over
the course of several weeks. The size, location, composition, structure, and
mechanical properties of the healing scar are all critical determinants of the
fate of patients who survive the initial infarction. While the central importance
of scar structure in determining pump function and remodeling has long been
recognized, it has proven remarkably difficult to design therapies that improve
heart function or limit remodeling by modifying scar structure. Many exciting new
therapies are under development, but predicting their long-term effects requires
a detailed understanding of how infarct scar forms, how its properties impact
left ventricular function and remodeling, and how changes in scar structure and
properties feed back to affect not only heart mechanics but also electrical
conduction, reflex hemodynamic compensations, and the ongoing process of scar
formation itself. In this article, we outline the scar formation process
following a myocardial infarction, discuss interpretation of standard measures of
heart function in the setting of a healing infarct, then present implications of
infarct scar geometry and structure for both mechanical and electrical function
of the heart and summarize experiences to date with therapeutic interventions
that aim to modify scar geometry and structure. One important conclusion that
emerges from the studies reviewed here is that computational modeling is an
essential tool for integrating the wealth of information required to understand
this complex system and predict the impact of novel therapies on scar healing,
heart function, and remodeling following myocardial infarction.
PMID- 26426478
TI - Hypocretin neuron-specific transcriptome profiling identifies the sleep modulator
Kcnh4a.
AB - Sleep has been conserved throughout evolution; however, the molecular and
neuronal mechanisms of sleep are largely unknown. The hypothalamic
hypocretin/orexin (Hcrt) neurons regulate sleep?wake states, feeding, stress, and
reward. To elucidate the mechanism that enables these various functions and to
identify sleep regulators, we combined fluorescence cell sorting and RNA-seq in
hcrt:EGFP zebrafish. Dozens of Hcrt-neuron-specific transcripts were identified
and comprehensive high-resolution imaging revealed gene-specific localization in
all or subsets of Hcrt neurons. Clusters of Hcrt-neuron-specific genes are
predicted to be regulated by shared transcription factors. These findings show
that Hcrt neurons are heterogeneous and that integrative molecular mechanisms
orchestrate their diverse functions. The voltage-gated potassium channel Kcnh4a,
which is expressed in all Hcrt neurons, was silenced by the CRISPR-mediated gene
inactivation system. The mutant kcnh4a (kcnh4a(-/-)) larvae showed reduced sleep
time and consolidation, specifically during the night, suggesting that Kcnh4a
regulates sleep.
PMID- 26426480
TI - Utilization and Outcomes of BRCA Genetic Testing and Counseling in a National
Commercially Insured Population: The ABOUT Study.
AB - IMPORTANCE: BRCA genetic testing has substantial public health impact, yet little
is known of the real-world experiences of the more than 100 000 Americans
undergoing testing annually. OBJECTIVE: To identify factors associated with use
of BRCA testing, assess whether delivery of genetic counseling and testing
services adheres to professional guidelines, and measure the impact on patient
reported outcomes. DESIGN, SETTING, AND PARTICIPANTS: The American BRCA Outcomes
and Utilization of Testing (ABOUT) Study analyzed data from a consecutive
national series of 11 159 women whose clinicians ordered BRCA testing between
December 2011 and December 2012. Aetna mailed recruitment information across the
United States to commercial health plan members whose clinicians had ordered BRCA
testing. A total of 3874 women (34.7%) completed questionnaires. Deidentified
clinician-reported data from all respondents and a random sample of 2613
nonrespondents were also analyzed. MAIN OUTCOMES AND MEASURES: The proportion of
eligible participants who met testing criteria and respondents' report of
receiving genetic counseling by a genetics clinician and its association with
BRCA knowledge, understanding, and satisfaction were assessed. RESULTS: Among
3628 women respondents whose clinicians ordered comprehensive BRCA testing, most
were white non-Hispanic (2502 [69.0%]), college educated (2953 [81.4%]), married
(2751 [75.8%]), and had higher incomes (2011 [55.4%]). Approximately 16.4% (596)
did not meet testing criteria. Mutations were identified in 161 (5.3%) of these
women who received comprehensive testing. Only 1334 (36.8%) reported receiving
genetic counseling from a genetics clinician prior to testing; the lowest rates
(130 [12.3%]) were among patients of obstetrician/gynecologists. The most
commonly reported reason for not receiving this clinical service was lack of
clinician recommendation. Those who received it demonstrated greater knowledge
about BRCA (mean score difference adjusted for demographics and clinician
specialty, beta = 0.99 [95% CI, 0.83-1.14]; P < .001) and expressed greater
understanding (beta = 0.47 [95% CI, 0.41-0.54]; P < .001) and satisfaction (beta
= 2.21 [95% CI, 1.60-2.81]; P < .001). CONCLUSIONS AND RELEVANCE: Despite
improved patient knowledge, understanding, and satisfaction among patients who
receive genetic counseling provided by a genetics clinician, as well as multiple
guidelines emphasizing the importance of genetic counseling, most US women
undergoing BRCA genetic testing do not receive this clinical service. Lack of
physician recommendation is the most commonly reported reason. These findings
demonstrate important gaps in clinical genetics services. Recently mandated
coverage of genetic counseling services as a preventive service without patient
cost sharing should contribute to improving clinical genetics services and
associated outcomes in the future.
PMID- 26426482
TI - TWO CASES OF ACUTE ENDOPHTHALMITIS AFTER INTRAVITREAL DEXAMETHASONE IMPLANT
INJECTION.
AB - PURPOSE: To present two cases of acute endophthalmitis after intravitreal
dexamethasone implant injection and discuss the management of intravitreal
implant-associated endophthalmitis. METHODS: Two patients, who underwent
intravitreal dexamethasone implant injection for macular edema secondary to
diabetic retinopathy in one and branch retinal vein occlusion in the other, were
admitted with decreased vision, pain, and redness in their treated eyes, 3 days
and 5 days after the injection, respectively. The clinical findings of both
patients were consistent with acute endophthalmitis. RESULTS: After obtaining
aqueous and vitreous samples, the patients were treated with intravitreal
antibiotic injection and topical fortified antibiotics. Both patients revealed
favorable clinical response and functional vision was recovered. CONCLUSION:
Intravitreal dexamethasone implant-associated endophthalmitis is an uncommon and
a challenging situation. Intravitreal antibiotics may lead to favorable visual
outcomes without the need for a pars plana vitrectomy and implant removal in
selected cases.
PMID- 26426479
TI - Evolutionary adaptation after crippling cell polarization follows reproducible
trajectories.
AB - Cells are organized by functional modules, which typically contain components
whose removal severely compromises the module's function. Despite their
importance, these components are not absolutely conserved between parts of the
tree of life, suggesting that cells can evolve to perform the same biological
functions with different proteins. We evolved Saccharomyces cerevisiae for 1000
generations without the important polarity gene BEM1. Initially the bem1?
lineages rapidly increase in fitness and then slowly reach >90% of the fitness of
their BEM1 ancestors at the end of the evolution. Sequencing their genomes and
monitoring polarization reveals a common evolutionary trajectory, with a fixed
sequence of adaptive mutations, each improving cell polarization by inactivating
proteins. Our results show that organisms can be evolutionarily robust to
physiologically destructive perturbations and suggest that recovery by gene
inactivation can lead to rapid divergence in the parts list for cell biologically
important functions.
PMID- 26426481
TI - Development of Novel, CNS Penetrant Positive Allosteric Modulators for the
Metabotropic Glutamate Receptor Subtype 1 (mGlu1), Based on an N-(3-Chloro-4-(1,3
dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide Scaffold, That
Potentiate Wild Type and Mutant mGlu1 Receptors Found in Schizophrenics.
AB - The therapeutic potential of selective mGlu1 activation is vastly unexplored
relative to the other group I mGlu receptor, mGlu5; therefore, our lab has
focused considerable effort toward developing mGlu1 positive allosteric
modulators (PAMs) suitable as in vivo proof of concept tool compounds.
Optimization of a series of mGlu1 PAMs based on an N-(3-chloro-4-(1,3
dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide scaffold provided 17e, a
potent (mGlu1 EC50 = 31.8 nM) and highly CNS penetrant (brain to plasma ratio
(Kp) of 1.02) mGlu1 PAM tool compound, that potentiated not only wild-type human
mGlu1 but also mutant mGlu1 receptors derived from deleterious GRM1 mutations
found in schizophrenic patients. Moreover, both electrophysiological and in vivo
studies indicate the mGlu1 ago-PAMs/PAMs do not possess the same epileptiform
adverse effect liability as mGlu5 ago-PAMs/PAMs and maintain temporal activity
suggesting a broader therapeutic window.
PMID- 26426483
TI - Gold-installed biostable nanocomplexes for tumor-targeted siRNA delivery in vivo.
AB - The key issues, associated with nanocarriers for small interfering RNAs (siRNAs),
are their poor stability and lack of tumor targetability in vivo. To address
these issues, we developed gold-installed polyethyleneimine/siRNA complexes with
a corona of PEGylated hyaluronic acid.
PMID- 26426484
TI - Excitation of Ni nanorod colloids in oscillating magnetic fields: a new approach
for nanosensing investigated by TISANE.
AB - The response of a colloidal dispersion of Ni nanorods to an oscillating magnetic
field was characterized by optical transmission measurements as well as small
angle neutron scattering (SANS) experiments using the TISANE (Time-dependent SANS
experiments) technique. Exposed to a static magnetic field, the scattering
intensity of the rod ensemble could be well described by the cylinder form factor
using the geometrical particle parameters (length, diameter, orientation
distribution) determined by transmission electronmicroscopy and magnetometry. An
oscillation of the field vector resulted in a reorientation of the nanorods and a
time-dependency of the scattering intensity due to the shape anisotropy of the
rods. Analysis of the SANS data revealed that in the range of low frequencies the
orientation distribution of the rods is comparable to the static case. With
increasing frequency, the rod oscillation was gradually damped due to an increase
of the viscous drag. It could be shown that despite of the increased friction in
the high frequency range no observable change of the orientation distribution of
the ensemble with respect to its symmetry axis occurs.
PMID- 26426485
TI - A modelling approach for MOF-encapsulated metal catalysts and application to n
butane oxidation.
AB - Metal nanoparticles (NP) encapsulated by metal-organic frameworks (MOFs) are
novel composite materials that have shown promise as regioselective catalysts.
The regioselectivity in these materials arises from steric constraints imposed by
the porous MOF structure, which limit the way molecules approach and interact
with the metal surface. Here we introduce a conceptually simple DFT approach to
model reactions under such steric constraints. This approach is computationally
efficient and accounts for the steric constraints imposed by a MOF pore in a
general way. The adsorption of reactants, intermediates, and products associated
with oxidation of n-butane to 1-butanol (and 2-butanol) on clean and oxygen
covered palladium surfaces is investigated with (and without) the constraints of
a pore. Reaction energies are calculated, and we find that the thermodynamic
favorability of the intermediate reactions is affected by the presence of steric
constraints, oxygen coverage, and the exposed crystal surface of the metal. Based
on these results, the Pd(111) surface with 0.25 ML oxygen coverage and steric
constraints (which could be provided by a suitable MOF) seems promising to favor
the desired sequence of reactions that would lead to the conversion of n-butane
to 1-butanol.
PMID- 26426486
TI - NanoSIMS analysis of an isotopically labelled organometallic ruthenium(II) drug
to probe its distribution and state in vitro.
AB - The in vitro inter- and intra-cellular distribution of an isotopically labelled
ruthenium(II)-arene (RAPTA) anti-metastatic compound in human ovarian cancer
cells was imaged using nano-scale secondary ion mass spectrometry (NanoSIMS).
Ultra-high resolution isotopic images of (13)C, (15)N, and Ru indicate that the
phosphine ligand remains coordinated to the ruthenium(II) ion whereas the arene
detaches. The complex localizes mainly on the membrane or at the interface
between cells which correlates with its anti-metastatic effects.
PMID- 26426487
TI - Profiling Private Water Systems to Identify Patterns of Waterborne Lead Exposure.
AB - Although extensive literature documents corrosion in municipal water systems,
only minimal data is available describing corrosion in private water systems
(e.g., wells), which serve as a primary source of drinking water for
approximately 47 million Americans. This study developed a profiling technique
specifically tailored to evaluate lead release in these systems. When applied in
an intensive field study of 15 private systems, three patterns of lead release
were documented: no elevated lead or lead elevated in the first draw only (Type
I), erratic spikes of particulate lead (Type II), and sustained detectable lead
concentrations (Type III). While flushing protocols as short as 15-30 s may be
sufficient to reduce lead concentrations below 15 MUg/L for Types I and III
exposure, flushing may not be an appropriate remediation strategy for Type II
exposure. In addition, the sustained detectable lead concentrations observed with
Type III exposure likely result from corrosion of components within the well and
therefore cannot be reduced with increased flushing. As profiling techniques are
labor- and sample-intensive, we discuss recommendations for simpler sampling
schemes for initial private system surveys aimed at quantifying lead and
protecting public health.
PMID- 26426488
TI - Editorial: Lessons From the Classic Scientific Literature.
PMID- 26426491
TI - Dielectric shell isolated and graphene shell isolated nanoparticle enhanced Raman
spectroscopies and their applications.
AB - Surface-enhanced Raman scattering (SERS) is a powerful technique that provides
fingerprint vibrational information with ultrahigh sensitivity. However, only a
few metals (gold, silver and copper) yield a large SERS effect, and they must be
rough at the nanoscale. Shell-isolated nanoparticle-enhanced Raman spectroscopy
(SHINERS) was developed to overcome the long-standing materials and morphological
limitations of SERS. It has already been applied in a variety of fields such as
materials science, electrochemistry, surface science, catalysis, food safety and
the life sciences. Here, the principles and applications of SHINERS are
highlighted. To provide an understanding of the plasmonics involved, finite
difference time-domain (FDTD) calculations and single nanoparticle SHINERS
experiments are reviewed. Next, various shell-isolated nanoparticle (SHIN) types
are described. Then a number of applications are discussed. In the first
application, SHINERS is used to characterize the adsorption processes of pyridine
on Au(hkl) single-crystal electrode surfaces. Then, SHINERS' applicability to
food inspection and cultural heritage science is demonstrated by the detection of
parathion and fenthion pesticides, and Lauth's violet (thionine dye). Finally,
graphene-isolated Au nanoparticles (GIANs) are shown to be effective for
multimodal cell imaging, photothermal cancer therapy and photothermally-enhanced
chemotherapy. SHINERS is a fast, simple and reliable method, suitable for
application to many areas of science and technology. The concept of shell
isolation can also be applied to other surface-enhanced spectroscopies such as
fluorescence, infrared absorption and sum frequency generation.
PMID- 26426492
TI - Fano Resonant Aluminum Nanoclusters for Plasmonic Colorimetric Sensing.
AB - Aluminum is an abundant and high-quality material for plasmonics with potential
for large-area, low-cost photonic technologies. Here we examine aluminum
nanoclusters with plasmonic Fano resonances that can be tuned from the near-UV
into the visible region of the spectrum. These nanoclusters can be designed with
specific chromaticities in the blue-green region of the spectrum and exhibit a
remarkable spectral sensitivity to changes in the local dielectric environment.
We show that such structures can be used quite generally for colorimetric
localized surface plasmon resonance (LSPR) sensing, where the presence of
analytes is detected by directly observable color changes rather than through
photodetectors and spectral analyzers. To quantify our results and provide a
metric for optimization of such structures for colorimetric LSPR sensing, we
introduce a figure of merit based on the color perception ability of the human
eye.
PMID- 26426499
TI - Selective 2'-hydroxyl acylation analyzed by primer extension and mutational
profiling (SHAPE-MaP) for direct, versatile and accurate RNA structure analysis.
AB - Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) chemistries
exploit small electrophilic reagents that react with 2'-hydroxyl groups to
interrogate RNA structure at single-nucleotide resolution. Mutational profiling
(MaP) identifies modified residues by using reverse transcriptase to misread a
SHAPE-modified nucleotide and then counting the resulting mutations by massively
parallel sequencing. The SHAPE-MaP approach measures the structure of large and
transcriptome-wide systems as accurately as can be done for simple model RNAs.
This protocol describes the experimental steps, implemented over 3 d, that are
required to perform SHAPE probing and to construct multiplexed SHAPE-MaP
libraries suitable for deep sequencing. Automated processing of MaP sequencing
data is accomplished using two software packages. ShapeMapper converts raw
sequencing files into mutational profiles, creates SHAPE reactivity plots and
provides useful troubleshooting information. SuperFold uses these data to model
RNA secondary structures, identify regions with well-defined structures and
visualize probable and alternative helices, often in under 1 d. SHAPE-MaP can be
used to make nucleotide-resolution biophysical measurements of individual RNA
motifs, rare components of complex RNA ensembles and entire transcriptomes.
PMID- 26426500
TI - Fabrication of nanopores with ultrashort single-walled carbon nanotubes inserted
in a lipid bilayer.
AB - We describe a protocol for the insertion of ultrashort single-walled carbon
nanotubes (SWCNTs) to form nanopores in a Montal-Mueller lipid bilayer. The
SWCNTs are designed to bind to a specific analyte of interest; binding will
result in the reduction of current in single-channel recording experiments. The
first stage of the PROCEDURE is to cut and separate the SWCNTs. We cut long,
purified SWCNTs with sonication in concentrated sulfuric acid/nitric acid (3/1).
Isolation of ultrashort SWCNTs is carried out by size-exclusion HPLC separation.
The second stage is to insert these short SWCNTs into the lipid bilayer. This
step requires a microinjection probe made from a glass capillary. The setup for
protein nanopore research can be adopted for the single-channel recording
experiments without any special treatment. The obtained current traces are of
very high quality, showing stable baselines and little background noise. Example
procedures are shown for investigating ion transport and DNA translocation
through these SWCNT nanopores. This nanopore has potential applications in
molecular sensing, nanopore DNA sequencing and early disease diagnosis. For
example, we have selectively detected modified 5-hydroxymethylcytosine in single
stranded DNA (ssDNA), which may have implications in screening specific genomic
DNA sequences. The protocol takes ~15 d, including SWCNT purification, cutting
and separation, as well as the formation of SWCNT nanopores for DNA analyses.
PMID- 26426501
TI - Efficient processing and analysis of large-scale light-sheet microscopy data.
AB - Light-sheet microscopy is a powerful method for imaging the development and
function of complex biological systems at high spatiotemporal resolution and over
long time scales. Such experiments typically generate terabytes of
multidimensional image data, and thus they demand efficient computational
solutions for data management, processing and analysis. We present protocols and
software to tackle these steps, focusing on the imaging-based study of animal
development. Our protocols facilitate (i) high-speed lossless data compression
and content-based multiview image fusion optimized for multicore CPU
architectures, reducing image data size 30-500-fold; (ii) automated large-scale
cell tracking and segmentation; and (iii) visualization, editing and annotation
of multiterabyte image data and cell-lineage reconstructions with tens of
millions of data points. These software modules are open source. They provide
high data throughput using a single computer workstation and are readily
applicable to a wide spectrum of biological model systems.
PMID- 26426503
TI - Photoelectrochemical properties of porphyrin dyes with a molecular dipole in the
linker.
AB - The electronic properties of three porphyrin-bridge-anchor photosensitizers are
reported with (1a, 1e, 3a and 3e) or without (2a and 2e) an intramolecular dipole
in the bridge. The presence and orientation of the bridge dipole is hypothesized
to influence the photovoltaic properties due to variations in the intrinsic
dipole at the semiconductor-molecule interface. Electrochemical studies of the
porphyrin-bridge-anchor dyes self-assembled on mesoporous nanoparticle ZrO2
films, show that the presence or direction of the bridge dipole does not have an
observable effect on the electronic properties of the porphyrin ring. Subsequent
photovoltaic measurements of nanostructured TiO2 semiconductor films in dye
sensitized solar cells show a reduced photocurrent for photosensitizers 1a and 3a
containing a bridge dipole. However, cooperative increased binding of the 1a + 3a
co-sensitized device demonstrates that dye packing overrides any differences due
to the presence of the small internal dipole.
PMID- 26426502
TI - Evidence synthesis in international development: a critique of systematic reviews
and a pragmatist alternative.
AB - Systematic reviews are an instrument of Evidence-Based Policy designed to produce
comprehensive, unbiased, transparent and clear assessments of interventions'
effectiveness. From their origins in medical fields, systematic reviews have
recently been promoted as offering important advances in a range of applied
social science fields, including international development. Drawing on a case
study of a systematic review of the effectiveness of community mobilisation as an
intervention to tackle HIV/AIDS, this article problematises the use of systematic
reviews to summarise complex and context-specific bodies of evidence. Social
development interventions, such as 'community mobilisation' often take different
forms in different interventions; are made successful by their situation in
particular contexts, rather than being successful or unsuccessful universally;
and have a rhetorical value that leads to the over-application of positively
valued terms (e.g. 'community mobilisation'), invalidating the keyword search
process of a systematic review. The article suggests that the policy interest in
definitive summary statements of 'the evidence' is at odds with academic
assessments that evidence takes multiple, contradictory and complex forms, and
with practitioner experience of the variability of practice in context. A
pragmatist philosophy of evidence is explored as an alternative. Taking this
approach implies expanding the definition of forms of research considered to be
'useful evidence' for evidence-based policy-making; decentralising decisions
about 'what works' to allow for the use of local practical wisdom; and
prioritising the establishment of good processes for the critical use of
evidence, rather than producing context-insensitive summaries of 'the evidence'.
PMID- 26426504
TI - Early management of neurologic clubfoot using Ponseti casting with minor
posterior release in myelomeningocele: a preliminary report.
AB - This study aimed to examine the results of manipulation and serial casting,
followed by open Achilles lengthening combined, when necessary, with posterior
release in the management of neurologic clubfoot in infants with
myelomeningocele. This study was carried out prospectively with a minimum follow
up of 2 years on 24 consecutive infants (48 feet) with neurologic insensate feet.
Manipulation and serial casting were performed, followed by open tendo Achilles
lengthening with/without posterior capsulotomy of the ankle and subtalar joints.
The Dimeglio scoring system was used to assess the degree of deformity correction
immediately postoperatively and the latest follow-up visits. The mean age of the
patients at initial treatment was 5.9 (3-8) weeks. None of the patients was lost
to follow-up. For 36 feet, the final range of scores was 5-6 and the deformities
were grade II of moderate type. Only for seven of 48 feet the final scores were
in the range 10-12, grade III, and severe type. Only three infants (5/48 feet)
failed to show any improvement. We thus support this treatment for the management
of insensate feet of infants with myelomeningocele soon after birth as most
infants responded satisfactorily in terms of deformity correction and achieved
plantigrade mobile feet that fit into orthotics.
PMID- 26426505
TI - Post-traumatic nonunion of a clavicle fracture in a 9-year-old child.
AB - Clavicular fractures account for around 15% of fractures in children. Although
nonunion is a recognized complication in adults, post-traumatic nonunion of the
clavicle in children is extremely rare. To the best of our knowledge, post
traumatic nonunion of the clavicle in a child following repeated clavicular
fracture has not yet been published in the English literature. Here, we report a
case of a 9-year-old boy who presented with post-traumatic nonunion of his right
clavicle following his third fracture after radiologically documented healing of
the first two fractures. He underwent open reduction and internal fixation,
supplemented with ipsilateral iliac crest bone graft, with resultant healing on
follow-up radiographs.
PMID- 26426506
TI - Salter-Harris type-IV displaced distal radius fracture in a 5-year-old.
AB - Displaced Salter-Harris type-IV fractures are rare in young children and can
result in articular incongruity or premature physeal arrest. We describe a 5-year
old boy who sustained a displaced left distal radial Salter-Harris type-IV
fracture. The patient had normal wrist function and physeal growth at the 3-year
postoperative follow-up. Our patient is by far the youngest reported child with a
displaced Salter-Harris type-IV fracture of the distal radius. Prompt anatomic
reduction and fixation of a displaced distal radial Salter-Harris type-IV
fracture can result in excellent short-term wrist motion with maintenance of
physeal function.
PMID- 26426507
TI - A modified Puddu technique for the treatment of adolescent mild to moderate tibia
vara.
AB - The aim of this work was to evaluate the results of a modified 'subphyseal' Puddu
technique for the treatment of selected cases of the adolescent tibia vara.
Twenty-five legs in 18 patients with adolescent tibia vara between January 2008
and February 2012 were included. The mean value of angular correction was 22.24
degrees (range, 18 degrees -25 degrees , SD 2.0 degrees ). All of the
osteotomies in this series healed by 8 weeks. There were no postoperative
neurologic or vascular complications. At the end of follow-up, no iatrogenic
disturbance to the proximal tibial physis was observed, but recurrence was
reported in three cases (12%). The modified 'subphyseal' Puddu technique is a
reproducible, easy, and convenient technique for the treatment of adolescent
tibia vara, provided there is proper case selection.
PMID- 26426508
TI - Fixator-augmented flexible intramedullary nailing for osteopenic femoral shaft
fractures in children.
AB - Children with underlying metabolic bone diseases, such as osteogenesis imperfecta
and spastic cerebral palsy, pose a challenge in the treatment of femoral shaft
fractures. We performed flexible intramedullary nailing with supplemental
monolateral external fixation in a subgroup of such patients. The external
fixator assists in controlling angulation and rotation at the fracture site, and
avoids the need for supplemental casting with its associated problems such as
skin breakdown and difficulty with personal hygiene. We describe the surgical
technique, pitfalls, and outcomes in a series of four patients with underlying
osteopenia treated with external fixator-augmented flexible nailing for femoral
shaft fractures.
PMID- 26426509
TI - Mesenchymal stem cells and serelaxin synergistically abrogate established airway
fibrosis in an experimental model of chronic allergic airways disease.
AB - This study determined if the anti-fibrotic drug, serelaxin (RLN), could augment
human bone marrow-derived mesenchymal stem cell (MSC)-mediated reversal of airway
remodeling and airway hyperresponsiveness (AHR) associated with chronic allergic
airways disease (AAD/asthma). Female Balb/c mice subjected to the 9-week model of
ovalbumin (OVA)-induced chronic AAD were either untreated or treated with MSCs
alone, RLN alone or both combined from weeks 9-11. Changes in airway inflammation
(AI), epithelial thickness, goblet cell metaplasia, transforming growth factor
(TGF)-beta1 expression, myofibroblast differentiation, subepithelial and total
lung collagen deposition, matrix metalloproteinase (MMP) expression, and AHR were
then assessed. MSCs alone modestly reversed OVA-induced subepithelial and total
collagen deposition, and increased MMP-9 levels above that induced by OVA alone
(all p<0.05 vs OVA group). RLN alone more broadly reversed OVA-induced epithelial
thickening, TGF-beta1 expression, myofibroblast differentiation, airway fibrosis
and AHR (all p<0.05 vs OVA group). Combination treatment further reversed OVA
induced AI and airway/lung fibrosis compared to either treatment alone (all
p<0.05 vs either treatment alone), and further increased MMP-9 levels. RLN
appeared to enhance the therapeutic effects of MSCs in a chronic disease setting;
most likely a consequence of the ability of RLN to limit TGF-beta1-induced matrix
synthesis complemented by the MMP-promoting effects of MSCs.
PMID- 26426510
TI - Hot Electron-Based Near-Infrared Photodetection Using Bilayer MoS2.
AB - Recently, there has been much interest in the extraction of hot electrons
generated from surface plasmon decay, as this process can be used to achieve
additional bandwidth for both photodetectors and photovoltaics. Hot electrons are
typically injected into semiconductors over a Schottky barrier between the metal
and semiconductor, enabling generation of photocurrent with below bandgap photon
illumination. As a two-dimensional semiconductor single and few layer molybdenum
disulfide (MoS2) has been demonstrated to exhibit internal photogain and
therefore becomes an attractive hot electron acceptor. Here, we investigate hot
electron-based photodetection in a device consisting of bilayer MoS2 integrated
with a plasmonic antenna array. We demonstrate sub-bandgap photocurrent
originating from the injection of hot electrons into MoS2 as well as
photoamplification that yields a photogain of 10(5). The large photogain results
in a photoresponsivity of 5.2 A/W at 1070 nm, which is far above similar silicon
based hot electron photodetectors in which no photoamplification is present. This
technique is expected to have potential use in future ultracompact near-infrared
photodetection and optical memory devices.
PMID- 26426514
TI - Reliability and validity of the 6-min walk test in adults and seniors with
intellectual disabilities.
AB - INTRODUCTION: Adults with intellectual disabilities (ID) have significantly lower
rates of physical activity and fitness than adults without ID. The 6-min walk
test (6 MWT) is an inexpensive and simple way to test mobility and submaximal
work capacity. PURPOSE: To evaluate the test-retest reliability and validity of
the 6 MWT in adults and seniors with ID and explore factors contributing to the 6
MWT distance (6 MWD). METHODS: 46 participants with mild, moderate and severe ID
levels (age=41 +/- 11 years) performed the 6 MWT three times (T1; T2; T3) to
determine test-retest reliability. To test validity, peak oxygen uptake (VO2
peak) was measured using a treadmill protocol. To analyze factors contributing to
the 6 MWD, sex, height, fat mass % and fat free mass %, ID level, isometric leg
strength and relative VO2 peak were also measured. RESULTS: The walking distances
for T1, T2 and T3 were 460.3 +/- 76.9; 489.4 +/- 81.2 and 491.4 +/- 77.9 m,
respectively. The 6 MWDs between T1-T2 and T1-T3 were significantly different
(p<0.001), but T2 and T3 were not different. The intraclass correlation
coefficient between T2 and T3 was 0.96 indicating high reliability. Relative VO2
peak and isometric leg strength significantly contributed to the 6 MWD
(R(2)=0.55). CONCLUSIONS: The 6 MWT is an easy, inexpensive, reliable and valid
test in adults and seniors with ID. Familiarization is necessary to obtain
reliable values. Relative VO2 peak and leg strength have significant impact on
the distance walked.
PMID- 26426516
TI - Investigation of stable germane structures under high-pressure.
AB - The evolutionary structure-searching method discovers that the energetically
preferred compounds of germane can be synthesized at a pressure of 190 GPa. New
structures with the space groups Ama2 and C2/c proposed here contain
semimolecular H2 and V-type H3 units, respectively. Electronic structure analysis
shows the metallic character and charge transfer from Ge to H. The conductivity
of the two structures originates from the electrons around the hydrogen atoms.
Further electron-phonon coupling calculations predict that the two phases are
superconductors with a high Tc of 47-57 K for Ama2 at 250 GPa and 70-84 K for
C2/c at 500 GPa from quasi-harmonic approximation calculations, which may be
higher than under actual conditions.
PMID- 26426515
TI - Ipsilesional motor-evoked potential absence in pediatric hemiparesis impacts
tracking accuracy of the less affected hand.
AB - This study analyzed the relationship between electrophysiological responses to
transcranial magnetic stimulation (TMS), finger tracking accuracy, and volume of
neural substrate in children with congenital hemiparesis. Nineteen participants
demonstrating an ipsilesional motor-evoked potential (MEP) were compared with
eleven participants showing an absent ipsilesional MEP response. Comparisons of
finger tracking accuracy from the affected and less affected hands and
ipsilesional/contralesional (I/C) volume ratio for the primary motor cortex (M1)
and posterior limb of internal capsule (PLIC) were done using two-sample t-tests.
Participants showing an ipsilesional MEP response demonstrated superior tracking
performance from the less affected hand (p=0.016) and significantly higher I/C
volume ratios for M1 (p=0.028) and PLIC (p=0.005) compared to participants
without an ipsilesional MEP response. Group differences in finger tracking
accuracy from the affected hand were not significant. These results highlight
differentiating factors amongst children with congenital hemiparesis showing
contrasting MEP responses: less affected hand performance and preserved M1 and
PLIC volume. Along with MEP status, these factors pose important clinical
implications in pediatric stroke rehabilitation. These findings may also reflect
competitive developmental processes associated with the preservation of affected
hand function at the expense of some function in the less affected hand.
PMID- 26426517
TI - The accuracy of clinical prediction of prognosis for patients admitted with
sepsis to internal medicine departments.
AB - INTRODUCTION: Prognosis estimation offered by physicians for patients inflicted
by sepsis on their admission to Internal Medicine (IM) departments is considered
a challenge. Early prognosis estimation is critical and determines the intensity
of treatment offered. The accuracy of prognosis estimation made by physicians has
previously been investigated mainly among intensive care physicians and
oncologists. OBJECTIVE: To ascertain the accuracy of prognosis prediction made by
internists for septic patients on admission to IM departments. METHODS:
Physicians were asked to estimate the prognosis of every patient identified to
have sepsis on admission. Their intuitive assessment of prognosis was
incorporated into the patients' electronic medical record. Survival follow-up was
recorded until death or for at least 2 years. Later we compared survival with
physicians' prognosis estimations. RESULTS: Prognosis estimation was recorded for
1,073 consecutive septic patients admitted throughout the years 2008-2009 to IM
departments. The mean age of patients was 74.7 +/- 16.1 years. A total of 42.4%
were suspected to have pneumonia, and 65.4% died during a mean follow-up time of
661.1 +/- 612.3 days. Almost half of the patients classified to have good
prognosis survived compared to 14.9% and 4.9% of those with intermediate and bad
prognosis estimation, respectively (P < 0.001). CONCLUSION: Internists can
discriminate well between septic patients with good, intermediate, and bad
prognosis.
PMID- 26426518
TI - The Adverse Effects of Motherhood on Substance Use Treatment Program Outcomes
Among Adolescent Women.
AB - OBJECTIVES: Adolescent mothers have differing risks and responsibilities compared
to adolescent women without children that may impact substance use treatment.
This study sought to describe characteristics of adolescent women in a substance
use treatment program and determine the effect of adolescent motherhood on
treatment program outcomes. METHODS: Data were collected from standardized
interviews of female adolescents in a case management criminal justice diversion
program for substance-using adolescents and adults. Variables included
sociodemographic factors (ie, race/ethnicity, age, financial support, education,
insurance, marital status, sexual abuse), Diagnostic and Statistical Manual-IV
(DSM-IV) substance use disorder diagnoses, and motherhood (ie, childbirth and
residence with a child). Treatment program outcome was documented by case workers
at the end of the participants' time in the program. Chi-square analyses and
analysis of variances determined associations between variables. Logistic
regression was used to assess characteristics associated with negative treatment
program outcome. RESULTS: Data from 1080 adolescent women aged 16-21 years (mean
19.7 years, SD = 1.16) were analyzed; 403 (37%) were mothers. After controlling
for sociodemographic factors and substance use disorder diagnoses, adolescent
mothers were less likely to successfully complete the treatment program than
nonmothers. Adolescent women with reliance on family or friends for financial
support, lower education status, and cannabis and cocaine use disorders had worse
treatment program outcomes. CONCLUSIONS: Childbirth and parenting adversely
affect substance use treatment outcomes for adolescent women in the criminal
justice system. Future research should explore tailored substance use treatments
for adolescents with children. Job training and educational support may improve
outcomes.
PMID- 26426519
TI - Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through
suppression of oxidative stress and apoptotic responses.
AB - The organ toxicity of doxorubicin (DOX), an anthracycline antineoplastic agent,
narrows the therapeutic window despite its clinical usefulness. In the present
study, we determined whether taurine protected against DOX-induced hepatic
injury, and explored the molecular mechanisms underlying the suppressive effects
of taurine in terms of alterations in oxidative stress and apoptotic responses.
DOX-induced body weight loss was completely suppressed by taurine treatment.
Elevations in the serum activity levels of lactate dehydrogenase, aspartate
aminotransferase, and alanine aminotransferase by DOX were also dose-dependently
attenuated by a concurrent treatment with taurine. Superoxide dismutase activity
and reduced glutathione content in the liver were decreased following the
administration of DOX, whereas these changes were suppressed when 10 mg/kg
taurine was given in combination with DOX. Taurine attenuated the increased
expression of mRNAs for Fas and Bax after DOX exposure. Furthermore, the
formation of cleaved caspase-3 protein in the group given DOX with taurine was
lower than that in the group treated with DOX alone. Our results suggest that
taurine can protect against DOX-induced acute hepatic damage, the underlying
mechanism of which is attributable to the suppression of oxidative stress and
apoptotic responses.
PMID- 26426520
TI - Comparison of the effectiveness of whole-brain radiotherapy plus temozolomide
versus whole-brain radiotherapy in treating brain metastases based on a
systematic review of randomized controlled trials.
AB - Temozolomide (TMZ) combination with whole-brain radiotherapy (WBRT) has been
tested by many randomized controlled trials in the treatment of brain metastases
(BMs) in China and other countries. We performed an up-to-date meta-analysis to
determine (i) the log odds ratios (LORs) of objective response (ORR) and adverse
effects (AEs) for all-grade, and (ii) the T value of mean overall survival in
patients with BMs treated with WBRT combined with TMZ versus WBRT alone. PubMed,
Chinese National Knowledge Infrastructure, and WanFang Data were searched for
articles published up to 28 January 2015. Eligible studies were selected
according to the PRISMA statement. ORR, AEs, and 95% confidence intervals were
calculated using random-effects models. Eighteen studies were included in our
analysis. A total of 1028 participants were enrolled. Summary LORs of ORR were
1.0239 (P<0.0001) on comparing WBRT plus TMZ with WBRT ORR (n=17). The overall
mean difference of mean overall survival (n=17) between TMZ plus WBRT and WBRT
was 2.2505 weeks (P=0.02185). There was a significant difference between WBRT
plus TMZ and WBRT alone with a LOR of AEs for all-grade of (i) 0.923 for
gastrointestinal toxicity and (ii) 0.7978 for myelosuppression. Sensitivity
analysis and subgroup analysis were also performed. The 18 eligible randomized
controlled trials demonstrated that the combination of WBRT and TMZ significantly
improves the ORR and is statistically insignificant in prolonging the survival of
patients with BMs. In addition, an increase in the incidence of gastrointestinal
toxicity and myelosuppression was significant for all-grade.
PMID- 26426521
TI - Synthesis and assessment of a maleimide functionalized BF2 azadipyrromethene near
infrared fluorochrome.
AB - The first water soluble maleimide bearing NIR BF2-azadipyrromethene (NIR-AZA)
fluorochrome has been synthesised which is capable of rapid thiol conjugations in
water with peptides such as glutathione, the cell penetrating peptide (CPP)
C(beta-A)SKKKKTKV-NH2 and a thiol substituted cRGD. NIR fluorescence imaging
showed rapid cellular delivery of the CPP conjugate and effective in vivo tumour
localization for the cRGD conjugate.
PMID- 26426523
TI - Mortality in adult immigrants in the 2000s in Belgium: a test of the 'healthy
migrant' and the 'migration-as-rapid-health-transition' hypotheses.
AB - OBJECTIVE: Firstly, to map out and compare all-cause and cause-specific mortality
patterns by migrant background in Belgium; and secondly, to probe into
explanations for the observed patterns, more specifically into the healthy
migrant, acculturation and the migration-as-rapid-health-transition theories.
METHODS: Data comprise individually linked Belgian census-mortality follow-up
data for the period 2001-2011. All official inhabitants aged 25-54 at time of the
census were included. To delve into the different explanations, differences in
all-cause and chronic- and infectious-disease mortality were estimated using
Poisson regression models, adjusted for age, socioeconomic position and
urbanicity. RESULTS: First-generation immigrants have lower all-cause and chronic
disease mortality than the host population. This mortality advantage wears off
with length of stay and is more marked among non-Western than Western first
generation immigrants. For example, Western and non-Western male immigrants
residing 10 years or more in Belgium have a mortality rate ratio for
cardiovascular disease of 0.72 (95% CI 0.66-0.78) and 0.59 (95% CI 0.53-0.66),
respectively (vs host population). The pattern of infectious-disease mortality in
migrants is slightly different, with rather high mortality rates in first
generation sub-Saharan Africans and rather low rates in all other immigrant
groups. As for second-generation immigrants, the picture is gloomier, with a
mortality disadvantage that disappears after control for socioeconomic position.
CONCLUSION: Findings are largely consistent with the healthy-migrant,
acculturation and the migration-as-rapid-health-transition theories. The
convergence of the mortality profile of second-generation immigrants towards that
of the host population with similar socioeconomic position indicates the need for
policies simultaneously addressing different areas of deprivation.
PMID- 26426522
TI - Restoration of Corticosteroid Sensitivity in Chronic Obstructive Pulmonary
Disease by Inhibition of Mammalian Target of Rapamycin.
AB - RATIONALE: Corticosteroid resistance is a major barrier to the effective
treatment of chronic obstructive pulmonary disease (COPD). Several molecular
mechanisms have been proposed, such as activations of the phosphoinositide-3
kinase/Akt pathway and p38 mitogen-activated protein kinase. However, the
mechanism for corticosteroid resistance is still not fully elucidated.
OBJECTIVES: To investigate the role of mammalian target of rapamycin (mTOR) in
corticosteroid sensitivity in COPD. METHODS: The corticosteroid sensitivity of
peripheral blood mononuclear cells collected from patients with COPD, smokers,
and nonsmoking control subjects, or of human monocytic U937 cells exposed to
cigarette smoke extract (CSE), was quantified as the dexamethasone concentration
required to achieve 30% inhibition of tumor necrosis factor-alpha-induced CXCL8
production in the presence or absence of the mTOR inhibitor rapamycin. mTOR
activity was determined as the phosphorylation of p70 S6 kinase, using Western
blotting. MEASUREMENTS AND MAIN RESULTS: mTOR activity was increased in
peripheral blood mononuclear cells from patients with COPD, and treatment with
rapamycin inhibited this as well as restoring corticosteroid sensitivity. In U937
cells, CSE stimulated mTOR activity and c-Jun expression, but pretreatment with
rapamycin inhibited both and also reversed CSE-induced corticosteroid
insensitivity. CONCLUSIONS: mTOR inhibition by rapamycin restores corticosteroid
sensitivity via inhibition of c-Jun expression, and thus mTOR is a potential
novel therapeutic target for COPD.
PMID- 26426525
TI - Intestinal amoebiasis in a patient with acute graft-versus-host disease after
allogeneic bone marrow transplantation successfully treated by metronidazole.
AB - Amoebiasis has rarely been reported in patients undergoing hematopoietic stem
cell transplantation, although it is a world-wide infection and extremely common.
We present a case of intestinal amoebiasis unexpectedly revealed by colonoscopy
after allogeneic bone marrow transplantation from a human leukocyte antigen
mismatched unrelated donor for acute myeloid leukemia arising from chronic
myelomonocytic leukemia and successfully treated by metronidazole.
PMID- 26426524
TI - Objective Assessment and Thematic Categorization of Patient-audible Information
in an Emergency Department.
AB - OBJECTIVES: The objective was to assess and categorize the understandable
components of patient-audible information (e.g., provider conversations) in
emergency department (ED) care areas and to initiate a baseline ED soundscape
assessment. METHODS: Investigators at an academic referral hospital accessed 21
deidentified transcripts of recordings made with binaural in-ear microphones in
patient rooms (n = 10) and spaces adjacent to nurses' stations (n = 11), during
ED staff sign-outs as part of an approved quality management process. Transcribed
materials were classified by speaker (health care provider,
patient/family/friend, or unknown). Using qualitative analysis software and
predefined thematic categories, two investigators then independently coded each
transcript by word, phrase, clause, and/or sentence for general content, patient
information, and HIPAA-defined patient identifiers. Scheduled reviews were used
to resolve any data coding discrepancies. RESULTS: Patient room recordings
featured a median of 11 (interquartile range [IQR] = 2 to 33) understandable
words per minute (wpm) over 16.2 (IQR = 15.1 to 18.4) minutes; nurses' station
recordings featured 74 (IQR = 47 to 109) understandable wpm over 17.0 (IQR = 15.4
to 20.3) minutes. Transcript content from patient room recordings was categorized
as follows: clinical, 44.8% (IQR = 17.7% to 62.2%); nonclinical, 0.0% (IQR = 0.0%
to 0.0%); inappropriate (provider), 0.0% (IQR = 0.0% to 0.0%); and unknown, 6.0%
(IQR = 1.7% to 58.2%). Transcript content from nurses' stations was categorized
as follows: clinical, 86.0% (IQR = 68.7% to 94.7%); nonclinical, 1.2% (IQR = 0.0%
to 19.5%); inappropriate (provider), 0.1% (IQR = 0.0% to 2.3%); and unknown, 1.3%
(IQR = 0.0% to 7.1%). Limited patient information was audible on patient room
recordings. Audible patient information at nurses' stations was coded as follows
(median words per sign-out sample): general patient history, 116 (IQR = 19 to
206); social history, 12 (IQR = 4 to 19); physical examination, 39 (IQR = 19 to
56); imaging results, 0 (IQR = 0 to 21); laboratory results, 7 (IQR = 0 to 22);
other results, 0 (IQR = 0 to 3); medical decision-making, 39 (IQR = 10 to 69);
management (general), 118 (IQR = 79 to 235); pain management, 4 (IQR = 0 to 53);
and disposition, 42 (IQR = 22 to 60). Medians of 0 (IQR = 0 to 0) and 3 (IQR = 1
to 4) patient name identifiers were audible on in-room and nurses' station sign
out recordings, respectively. CONCLUSIONS: Sound recordings in an ED setting
captured audible and understandable provider discussions that included
confidential, protected health information and discernible quantities of
nonclinical content.
PMID- 26426526
TI - Diversification of sterol methyltransferase enzymes in plants and a role for beta
sitosterol in oriented cell plate formation and polarized growth.
AB - Phytosterols are classified into C24-ethylsterols and C24-methylsterols according
to the different C24-alkylation levels conferred by two types of sterol
methyltransferases (SMTs). The first type of SMT (SMT1) is widely conserved,
whereas the second type (SMT2) has diverged in charophytes and land plants. The
Arabidopsis smt2 smt3 mutant is defective in the SMT2 step, leading to deficiency
in C24-ethylsterols while the C24-methylsterol pathway is unchanged. smt2 smt3
plants exhibit severe dwarfism and abnormal development throughout their life
cycle, with irregular cell division followed by collapsed cell files. Preprophase
bands are occasionally formed in perpendicular directions in adjacent cells, and
abnormal phragmoplasts with mislocalized KNOLLE syntaxin and tubulin are
observed. Defects in auxin-dependent processes are exemplified by
mislocalizations of the PIN2 auxin efflux carrier due to disrupted cell division
and failure to distribute PIN2 asymmetrically after cytokinesis. Although
endocytosis of PIN2-GFP from the plasma membrane (PM) is apparently unaffected in
smt2 smt3, strong inhibition of the endocytic recycling is associated with a
remarkable reduction in the level of PIN2-GFP on the PM. Aberrant localization of
the cytoplasmic linker associated protein (CLASP) and microtubules is implicated
in the disrupted endocytic recycling in smt2 smt3. Exogenous C24-ethylsterols
partially recover lateral root development and auxin distribution in smt2 smt3
roots. These results indicate that C24-ethylsterols play a crucial role in
division plane determination, directional auxin transport, and polar growth. It
is proposed that the divergence of SMT2 genes together with the ability to
produce C24-ethylsterols were critical events to achieve polarized growth in the
plant lineage.
PMID- 26426527
TI - Motor Vehicle Crashes, Medical Outcomes, and Hospital Charges Among Children Aged
1-12 Years - Crash Outcome Data Evaluation System, 11 States, 2005-2008.
AB - PROBLEM: Motor vehicle crashes are a leading cause of death among children. Age-
and size-appropriate restraint use is an effective way to prevent motor vehicle
related injuries and deaths. However, children are not always properly restrained
while riding in a motor vehicle, and some are not restrained at all, which
increases their risk for injury and death in a crash. REPORTING PERIOD: 2005
2008. DESCRIPTION OF THE SYSTEM: The Crash Outcome Data Evaluation System (CODES)
is a multistate program facilitated by the National Highway Traffic Safety
Administration to probabilistically link police crash reports and hospital
databases for traffic safety analyses. Eleven participating states (Connecticut,
Georgia, Kentucky, Maryland, Minnesota, Missouri, Nebraska, New York, Ohio, South
Carolina, and Utah) submitted data to CODES during the reporting period.
Descriptive analysis was used to describe drivers and child passengers involved
in motor vehicle crashes and to summarize crash and medical outcomes. Odds ratios
and 95% confidence intervals were used to compare a child passenger's likelihood
of sustaining specific types of injuries by restraint status (optimal,
suboptimal, or unrestrained) and seating location (front or back seat). Because
of data constraints, optimal restraint use was defined as a car seat or booster
seat use for children aged 1-7 years and seat belt use for children aged 8-12
years. Suboptimal restraint use was defined as seat belt use for children aged 1
7 years. Unrestrained was defined as no use of car seat, booster seat, or seat
belt for children aged 1-12 years. RESULTS: Optimal restraint use in the back
seat declined with child's age (1 year: 95.9%, 5 years: 95.4%, 7 years: 94.7%, 8
years: 77.4%, 10 years: 67.5%, 12 years: 54.7%). Child restraint use was
associated with driver restraint use; 41.3% of children riding with unrestrained
drivers also were unrestrained compared with 2.2% of children riding with
restrained drivers. Child restraint use also was associated with impaired driving
due to alcohol or drug use; 16.4% children riding with drivers suspected of
alcohol or drug use were unrestrained compared with 2.9% of children riding with
drivers not suspected of such use. Optimally restrained and suboptimally
restrained children were less likely to sustain a traumatic brain injury than
unrestrained children. The 90th percentile hospital charges for children aged 4-7
years who were in motor vehicle crashes were $1,630.00 and $1,958.00 for those
optimally restrained in a back seat and front seat, respectively; $2,035.91 and
$3,696.00 for those suboptimally restrained in a back seat and front seat,
respectively; and $9,956.60 and $11,143.85 for those unrestrained in a back seat
and front seat, respectively. INTERPRETATION: Proper car seat, booster seat, and
seat belt use among children in the back seat prevents injuries and deaths, as
well as averts hospital charges. However, the number, severity, and cost of
injuries among children in crashes who were not optimally restrained or who were
seated in a front seat indicates the need for improvements in proper use of age-
and size-appropriate car seats, booster seats, and seat belts in the back seat.
PUBLIC HEALTH ACTIONS: Effective interventions for increasing proper child
restraint use could be universally implemented by states and communities to
prevent motor vehicle-related injuries among children and their resulting costs.
PMID- 26426528
TI - Nitrate, nitrite and nitric oxide reductases: from the last universal common
ancestor to modern bacterial pathogens.
AB - The electrochemical gradient that ensues from the enzymatic activity of
cytochromes such as nitrate reductase, nitric oxide reductase, and quinol oxidase
contributes to the bioenergetics of the bacterial cell. Reduction of nitrogen
oxides by bacterial pathogens can, however, be uncoupled from proton
translocation and biosynthesis of ATP or NH4(+), but still linked to quinol and
NADH oxidation. Ancestral nitric oxide reductases, as well as cytochrome c
oxidases and quinol bo oxidases evolved from the former, are capable of binding
and detoxifying nitric oxide to nitrous oxide. The NO-metabolizing activity
associated with these cytochromes can be a sizable source of antinitrosative
defense in bacteria during their associations with host cells. Nitrosylation of
terminal cytochromes arrests respiration, reprograms bacterial metabolism,
stimulates antioxidant defenses and alters antibiotic cytotoxicity. Collectively,
the bioenergetics and regulation of redox homeostasis that accompanies the
utilization of nitrogen oxides and detoxification of nitric oxide by cytochromes
of the electron transport chain increases fitness of many Gram-positive and
negative pathogens during their associations with invertebrate and vertebrate
hosts.
PMID- 26426529
TI - Peripheral Nerve Transplantation Combined with Acidic Fibroblast Growth Factor
and Chondroitinase Induces Regeneration and Improves Urinary Function in Complete
Spinal Cord Transected Adult Mice.
AB - The loss of lower urinary tract (LUT) control is a ubiquitous consequence of a
complete spinal cord injury, attributed to a lack of regeneration of supraspinal
pathways controlling the bladder. Previous work in our lab has utilized a
combinatorial therapy of peripheral nerve autografts (PNG), acidic fibroblast
growth factor (aFGF), and chondroitinase ABC (ChABC) to treat a complete T8
spinal cord transection in the adult rat, resulting in supraspinal control of
bladder function. In the present study we extended these findings by examining
the use of the combinatorial PNG+aFGF+ChABC treatment in a T8 transected mouse
model, which more closely models human urinary deficits following spinal cord
injury. Cystometry analysis and external urethral sphincter electromyograms
reveal that treatment with PNG+aFGF+ChABC reduced bladder weight, improved
bladder and external urethral sphincter histology, and significantly enhanced LUT
function, resulting in more efficient voiding. Treated mice's injured spinal cord
also showed a reduction in collagen scaring, and regeneration of serotonergic and
tyrosine hydroxylase-positive axons across the lesion and into the distal spinal
cord. Regeneration of serotonin axons correlated with LUT recovery. These results
suggest that our mouse model of LUT dysfunction recapitulates the results found
in the rat model and may be used to further investigate genetic contributions to
regeneration failure.
PMID- 26426530
TI - The Impact of Misuse and Diversion of Opioid Substitution Treatment Medicines:
Evidence Review and Expert Consensus.
AB - BACKGROUND/AIMS: Opioid substitution treatment (OST) improves outcomes in opioid
dependence. However, controlled drugs used in treatment may be misused or
diverted, resulting in negative treatment outcomes. This review defines a
framework to assess the impact of misuse and diversion. METHODS: A systematic
review of published studies of misuse and diversion of OST medicines was
completed; this evidence was paired with expert real-world experience to better
understand the impact of misuse and diversion on the individual and on society.
RESULTS: Direct impact to the individual includes failure to progress in recovery
and negative effects on health (overdose, health risks associated with injecting
behaviour). Diversion of OST has impacts on a community that is beyond the
intended OST recipient. The direct impact includes risk to others (unsupervised
use; unintended exposure of children to diverted medication) and drug-related
criminal behavior. The indirect impact includes the economic costs of untreated
opioid dependence, crime and loss of productivity. CONCLUSION: While treatment
for opioid dependence is essential and must be supported, it is vital to reduce
misuse and diversion while ensuring the best possible care. Understanding the
impact of OST misuse and diversion is key to defining strategies to address these
issues.
PMID- 26426531
TI - Efficacy of Procyanidins against In Vivo Cellular Oxidative Damage: A Systematic
Review and Meta-Analysis.
AB - AIMS: In this study, the efficacy of proanthocyanidins (PCs) against oxidative
damage was systematically reviewed to facilitate their use in various
applications. METHODS: A meta-analysis was performed by two researchers. Each
investigator independently searched electronic databases, including Cochrane,
PubMed, Springer, Web of Science, China National Knowledge Infrastructure (CKNI),
China Science and Technology Journal Database (CSTJ), and WanFang Data, and
analyzed published data from 29 studies on the effects of PCs against oxidative
damage. Oxidative stress indexes included superoxide dismutase (SOD),
malondialdehyde (MDA), catalase (CAT), glutathione (GSH), glutathione peroxidase
(GPx), and total antioxidative capacity (T-AOC). RESULTS: Compared with the
oxidative damage model group, PCs effectively improved the T-AOC, SOD, GSH, GPx,
and CAT levels, and reduced the MDA levels; these differences were statistically
significant (P < 0.05). In studies that used the gavage method, SOD (95% CI, 2.33
4.00) and GPx (95% CI, 2.10-4.05) were 3.16-fold and 3.08-fold higher in the PC
group than in the control group, respectively. In studies that used the feeding
method, SOD (95% CI, 0.32-1.74) and GPx (95% CI, -0.31 to 1.65) were 1.03-fold
and 0.67-fold higher in the PC group than in the control group, respectively.
Statistically significant differences in the effects of PCs (P < 0.00001) were
observed between these two methods. MDA estimated from tissue samples (95% CI,
5.82 to -2.60) was 4.32-fold lower in the PC group than in the control group. In
contrast, MDA estimated using serum samples (95% CI, -4.07 to -2.06) was 3.06
fold lower in the PC group than in the control group. The effect of PCs on MDA
was significantly greater in tissue samples than in serum samples (P = 0.02).
CONCLUSION: PCs effectively antagonize oxidative damage and enhance antioxidant
capacity. The antagonistic effect may be related to intervention time,
intervention method, and the source from which the indexes are estimated.
PMID- 26426532
TI - Mapping Above- and Below-Ground Carbon Pools in Boreal Forests: The Case for
Airborne Lidar.
AB - A large and growing body of evidence has demonstrated that airborne scanning
light detection and ranging (lidar) systems can be an effective tool in measuring
and monitoring above-ground forest tree biomass. However, the potential of lidar
as an all-round tool for assisting in assessment of carbon (C) stocks in soil and
non-tree vegetation components of the forest ecosystem has been given much less
attention. Here we combine the use airborne small footprint scanning lidar with
fine-scale spatial C data relating to vegetation and the soil surface to describe
and contrast the size and spatial distribution of C pools within and among
multilayered Norway spruce (Picea abies) stands. Predictor variables from lidar
derived metrics delivered precise models of above- and below-ground tree C, which
comprised the largest C pool in our study stands. We also found evidence that
lidar canopy data correlated well with the variation in field layer C stock,
consisting mainly of ericaceous dwarf shrubs and herbaceous plants. However,
lidar metrics derived directly from understory echoes did not yield significant
models. Furthermore, our results indicate that the variation in both the mosses
and soil organic layer C stock plots appears less influenced by differences in
stand structure properties than topographical gradients. By using topographical
models from lidar ground returns we were able to establish a strong correlation
between lidar data and the organic layer C stock at a stand level. Increasing the
topographical resolution from plot averages (~2000 m2) towards individual grid
cells (1 m2) did not yield consistent models. Our study demonstrates a connection
between the size and distribution of different forest C pools and models derived
from airborne lidar data, providing a foundation for future research concerning
the use of lidar for assessing and monitoring boreal forest C.
PMID- 26426533
TI - Rheumatoid Arthritis Risk Associated with Periodontitis Exposure: A Nationwide,
Population-Based Cohort Study.
AB - BACKGROUND: The risk of periodontitis (PD) is increased in the patient group of
rheumatoid arthritis (RA). RA and PD also shared some pathological mechanism. The
aim of this study is to investigate the risk of RA associated with PD exposure.
METHODS AND FINDINGS: This study identified 3 mutually exclusive cohorts using
the 1999-2010 Taiwanese National Health Insurance Research Database (NHIRD) to
investigate the association between PD and the risk of incident RA. All patients
with PD in 2000 were identified from the database of all enrollees as the PD
cohort. From the representative database of 1,000,000 enrollees randomly selected
in 2010 (LHID2010), individuals without any periodontal disease (PO) during 1999
2010 were selected as the non-PO cohort. Individuals who were not included in the
non-PO cohort and received dental scaling (DS) no more than two times per year
during 1999-2010 were selected as the DS cohort from LHID2010. Using cox
proportional regression analysis, hazard ratios (HRs) with 95% confidence
intervals (Cis) were calculated to quantify the association between PD exposure
and RA development. In the three-group comparison using the non-PO cohort as
reference, we found that the risk of RA was higher in the PD and DS cohorts (HRs,
1.89 and 1.43; 95% CIs, 1.56-2.29 and 1.09-1.87, respectively). For comparisons
between two cohorts, the PD cohort had a higher risk of RA than the non-PO and DS
cohorts (HRs, 1.91 and 1.35; 95% CIs, 1.57-2.30 and 1.09-1.67, respectively).
CONCLUSION: PD was associated with an increased risk of RA development.
PMID- 26426534
TI - Hemispheric lateralization in reasoning.
AB - A growing body of evidence suggests that reasoning in humans relies on a number
of related processes whose neural loci are largely lateralized to one hemisphere
or the other. A recent review of this evidence concluded that the patterns of
lateralization observed are organized according to two complementary tendencies.
The left hemisphere attempts to reduce uncertainty by drawing inferences or
creating explanations, even at the cost of ignoring conflicting evidence or
generating implausible explanations. Conversely, the right hemisphere aims to
reduce conflict by rejecting or refining explanations that are no longer tenable
in the face of new evidence. In healthy adults, the hemispheres work together to
achieve a balance between certainty and consistency, and a wealth of
neuropsychological research supports the notion that upsetting this balance
results in various failures in reasoning, including delusions. However, support
for this model from the neuroimaging literature is mixed. Here, we examine the
evidence for this framework from multiple research domains, including an
activation likelihood estimation analysis of functional magnetic resonance
imaging studies of reasoning. Our results suggest a need to either revise this
model as it applies to healthy adults or to develop better tools for assessing
lateralization in these individuals.
PMID- 26426535
TI - Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced
Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice.
AB - Plasma gelsolin levels significantly decline in several disease conditions, since
gelsolin gets scavenged when it depolymerizes and caps filamentous actin released
in the circulation following tissue injury. It is well established that our body
require/implement inflammatory and analgesic responses to protect against cell
damage and injury to the tissue. This study was envisaged to examine analgesic
and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse) in mice models
of pain and acute inflammation. Administration of gelsolin in acetic acid-induced
writhing and tail immersion tests not only demonstrated a significant reduction
in the number of acetic acid-induced writhing effects, but also exhibited an
analgesic activity in tail immersion test in mice as compared to placebo treated
mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse) compared
with anti-inflammatory drug diclofenac sodium (10 mg/kg)] was confirmed in the
carrageenan injection induced paw edema where latter was measured by vernier
caliper and fluorescent tomography imaging. Interestingly, results showed that
plasma gelsolin was capable of reducing severity of inflammation in mice
comparable to diclofenac sodium. Analysis of cytokines and histopathological
examinations of tissue revealed administration of gelsolin and diclofenac sodium
significantly reduced production of pro-inflammatory cytokines, TNF-alpha and IL
6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin
showed a marked decrease in edema and infiltration of inflammatory cells in paw
tissue. Our study provides evidence that administration of gelsolin can
effectively reduce the pain and inflammation in mice model.
PMID- 26426536
TI - Ornithine Decarboxylase Activity Is Required for Prostatic Budding in the
Developing Mouse Prostate.
AB - The prostate is a male accessory sex gland that produces secretions in seminal
fluid to facilitate fertilization. Prostate secretory function is dependent on
androgens, although the mechanism by which androgens exert their effects is still
unclear. Polyamines are small cationic molecules that play pivotal roles in DNA
transcription, translation and gene regulation. The rate-limiting enzyme in
polyamine biosynthesis is ornithine decarboxylase, which is encoded by the gene
Odc1. Ornithine decarboxylase mRNA decreases in the prostate upon castration and
increases upon administration of androgens. Furthermore, testosterone
administered to castrated male mice restores prostate secretory activity, whereas
administering testosterone and the ornithine decarboxylase inhibitor D,L-alpha
difluromethylornithine (DFMO) to castrated males does not restore prostate
secretory activity, suggesting that polyamines are required for androgens to
exert their effects. To date, no one has examined polyamines in prostate
development, which is also androgen dependent. In this study, we showed that
ornithine decarboxylase protein was expressed in the epithelium of the ventral,
dorsolateral and anterior lobes of the adult mouse prostate. Ornithine
decarboxylase protein was also expressed in the urogenital sinus (UGS) epithelium
of the male and female embryo prior to prostate development, and expression
continued in prostatic epithelial buds as they emerged from the UGS. Inhibiting
ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of
prostatic buds by androgens, and significantly decreased expression of key
prostate transcription factor, Nkx3.1, by androgens. DFMO also significantly
decreased the expression of developmental regulatory gene Notch1. Other genes
implicated in prostatic development including Sox9, Wif1 and Srd5a2 were
unaffected by DFMO. Together these results indicate that Odc1 and polyamines are
required for androgens to exert their effect in mediating prostatic bud
induction, and are required for the expression of a subset of prostatic
developmental regulatory genes including Notch1 and Nkx3.1.
PMID- 26426538
TI - Social Capital as a Determinant of Pregnant Mother's Place of Delivery:
Experience from Kongwa District in Central Tanzania.
AB - INTRODUCTION: Maternal ill health contributes highly to the global burden of
diseases in countries South of Sahara including Tanzania. Ensuring that all
deliveries take place in health facilities and hence attended by skilled health
personnel is one of the strategies advocated by global and national policies,
including the Millennium Development Goals (MDGs). However, the number of women
delivered by skilled health personnel has remained low in sub Saharan Africa
despite of a number of interventions. We sought to determine the role of social
capital in facilitating health facility delivery. METHODS: We randomly selected
744 households with children aged less than five years from two randomly selected
wards in a rural area in Tanzania. Mothers were enquired about place of delivery
of the last child. Social capital was assessed using a modified questionnaire
with both structural and cognitive aspects of social capital, administered in
face-to-face interviews. Principal Component Analysis (PCA) was used to develop
asocial capital index measure. Uni-variate and multivariable regression models
were run using STATA 12. RESULTS: Majority (85.9%) of the mothers reported to
have delivered in a health facility during their last birth. Compared to the
lowest social capital quintile, delivering in a health facility increased
significantly with increase in social capital level: low (Adjusted Odds Ratio
(AOR) = 2.9; Confidence Interval (CI): 1.4-6.1, p = 0.004); moderate (AOR = 5.5,
CI: 2.3-13.3, p-value<0.001); high (AOR = 4.7; CI: 1.9-11.6, p-value<0.001) and
highest (AOR = 5.6, CI: 2.4-13.4, p-value<0.001) and chi2-test for the trend was
significant (chi2 = 17.21, p<0.001). CONCLUSION: Overall, social capital seems to
play an important role in enhancing health facility delivery that may lead to
improved maternal and child health. Concerted efforts should focus on promoting
and supporting effective social capital and in particular cognitive social
capital.
PMID- 26426539
TI - Shifts in functional traits elevate risk of fire-driven tree dieback in tropical
savanna and forest biomes.
AB - Numerous predictions indicate rising CO2 will accelerate the expansion of forests
into savannas. Although encroaching forests can sequester carbon over the short
term, increased fires and drought-fire interactions could offset carbon gains,
which may be amplified by the shift toward forest plant communities more
susceptible to fire-driven dieback. We quantify how bark thickness determines the
ability of individual tree species to tolerate fire and subsequently determine
the fire sensitivity of ecosystem carbon across 180 plots in savannas and forests
throughout the 2.2-million km(2) Cerrado region in Brazil. We find that not
accounting for variation in bark thickness across tree species underestimated
carbon losses in forests by ~50%, totaling 0.22 PgC across the Cerrado region.
The lower bark thicknesses of plant species in forests decreased fire tolerance
to such an extent that a third of carbon gains during forest encroachment may be
at risk of dieback if burned. These results illustrate that consideration of
trait-based differences in fire tolerance is critical for determining the climate
carbon-fire feedback in tropical savanna and forest biomes.
PMID- 26426537
TI - Reversal of multidrug resistance by co-delivery of paclitaxel and lonidamine
using a TPGS and hyaluronic acid dual-functionalized liposome for cancer
treatment.
AB - Multidrug resistance (MDR) remains the primary issue in cancer therapy, which is
characterized by the overexpressed P-glycoprotein (P-gp)-included efflux pump or
the upregulated anti-apoptotic proteins. In this study, a D-alpha-tocopheryl poly
(ethylene glycol 1000) succinate (TPGS) and hyaluronic acid (HA) dual
functionalized cationic liposome containing a synthetic cationic lipid, 1,5
dioctadecyl-N-histidyl-L-glutamate (HG2C18) was developed for co-delivery of a
small-molecule chemotherapeutic drug, paclitaxel (PTX) with a chemosensitizing
agent, lonidamine (LND) to treat the MDR cancer. It was demonstrated that the
HG2C18 lipid contributes to the endo-lysosomal escape of the liposome following
internalization for efficient intracellular delivery. The TPGS component was
confirmed able to elevate the intracellular accumulation of PTX by inhibiting the
P-gp efflux, and to facilitate the mitochondrial-targeting of the liposome. The
intracellularly released LND suppressed the intracellular ATP production by
interfering with the mitochondrial function for enhanced P-gp inhibition, and
additionally, sensitized the MDR breast cancer (MCF-7/MDR) cells to PTX for
promoted induction of apoptosis through a synergistic effect. Functionalized with
the outer HA shell, the liposome preferentially accumulated at the tumor site and
showed a superior antitumor efficacy in the xenograft MCF-7/MDR tumor mice
models. These findings suggest that this dual-functional liposome for co-delivery
of a cytotoxic drug and an MDR modulator provides a promising strategy for
reversal of MDR in cancer treatment.
PMID- 26426540
TI - Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving
Intravenously Administered Gentamicin.
AB - BACKGROUND: Gentamicin is an aminoglycoside antimicrobial commonly used in horses
at 6.6 mg/kg IV once daily. Therapeutic drug monitoring (TDM) can confirm desired
peak concentration is reached for common bacterial isolates, and detect toxicosis
associated with high trough values. OBJECTIVES: Determine the relationship
between gentamicin dose and plasma concentration in hospitalized horses, and
identify a starting dose range to achieve peaks > 32 MUg/mL. ANIMALS: Sixty-five
horses (2002-2010) receiving once-daily gentamicin with TDM performed (N = 99
sets). METHODS: Retrospective study. Data from hospitalized horses including
weight, dose, plasma peak, and trough gentamicin concentration, creatinine
concentrations and presence of focal or systemic disease were collected from
medical records. Peak concentrations measured 25-35 minutes after administration
were included (N = 77). Data were divided into low (<7.7 mg/kg), medium (7.7-9.7
mg/kg) and high (>9.7 mg/kg) dose groups, and were grouped by the horse having
focal or systemic disease. RESULTS: Peak concentrations resulting from doses
>=7.7 mg/kg were 5.74 MUg/mL (SE 2.1 MUg/mL) greater than peaks from doses <7.7
mg/kg (P = .007). Peak concentrations was 3.6 times more likely to be >32 MUg/mL
if dose was >=7.7 mg/kg (P = .04). There were no significant effects of dose on
trough or creatinine concentration. At a given dose, horses with focal disease
had higher peaks than those with systemic disease (P = .039). CONCLUSIONS AND
CLINICAL IMPORTANCE: These data suggest gentamicin dosage should be individually
determined in horses using TDM, but support an initial once-daily dose of 7.7-9.7
mg/kg IV to achieve peaks >32 MUg/mL and trough concentrations <2 MUg/mL. Further
studies evaluating the safety of doses >6.6 mg/kg are required.
PMID- 26426541
TI - Rod-to-Globule Transition of pDNA/PEG-Poly(l-Lysine) Polyplex Micelles Induced by
a Collapsed Balance Between DNA Rigidity and PEG Crowdedness.
AB - The role of poly(ethylene-glycol) (PEG) in rod-shaped polyplex micelle
structures, having a characteristic core of folded plasmid DNA (pDNA) and a shell
of tethered PEG chains, is investigated using PEG-detachable polyplex micelles.
Rod shapes undergo change to compacted globule shapes by removal of PEG from
polyplex micelles prepared from block copolymer with acid-labile linkage between
PEG and poly(l-lysine) (PLys) through exposure to acidic milieu. This structural
change supports the previous investigation on the rod shapes that PEG shell
prevents the DNA structure from being globule shaped as the most favored
structure in minimizing surface area. Noteworthy, despite the PEG is continuously
depleted, the structural change does not occur in gradual shortening manner but
the rod shapes keep their length unchanged and abruptly transform into globule
shapes. Analysis of PEG density reveals the transition occurred when tethered PEG
of rod shapes has decreased to a critical crowdedness, i.e., discontacted with
neighboring PEG, which eventually illuminates another contribution, rigidity of
DNA packaged as bundle in the rod shapes, in addition to the steric repulsion of
PEG, in sustaining rod shapes. This investigation affirms significant role of PEG
and also DNA rigidity as bundle in the formation of rod-shaped structures
enduring the quest of compaction of charge-neutralized DNA in the polyplex
micelles.
PMID- 26426542
TI - Recent applications of CE- and HPLC-MS in the analysis of human fluids.
AB - The present review intends to cover the literature on the use of CE-/LC-MS for
the analysis of human fluids, from 2010 until present. It has been planned to
provide an overview of the most recent practical applications of these techniques
to less extensively used human body fluids, including, bronchoalveolar lavage
fluid, synovial fluid, nipple aspirate, tear fluid, breast fluid, amniotic fluid,
and cerumen. Potential pitfalls related to fluid collection and sample
preparation, with particular attention to sample clean-up procedures, and methods
of analysis, from the research laboratory to a clinical setting will also be
addressed. While being apparent that proteomics/metabolomics represent the most
prominent approaches for global identification/quantification of putative
biomarkers for a variety of human diseases, evidence is also provided of the
suitability of these sophisticated techniques for the detection of heterogeneous
components carried by these fluids.
PMID- 26426543
TI - Preparation of silicon-modified antimicrobial polyethylene endotracheal tubes.
AB - Antimicrobial coating of polyethylene endotracheal tubes (PE ETTs) has proven to
be an effective method to prevent endoluminal biofilm formation. A transparent
silicon-modified antimicrobial PE ETT was obtained by coating PE with a SiO2
/gamma-methacryloxypropyl trimethoxy silane (KH-570)/methyltriethoxysilane
(MTES)/Ag-SiO2 solution prepared by chemically mixing Ag-SiO2 with SiO2 /KH
570/MTES in solution via a dip-coating method, with tetraethyl orthosilicate
(TEOS) as the inorganic silicon source, followed by drying. All the films were
characterized by various techniques, including the pencil hardness test, infrared
spectroscopy, scanning electron microscopy, UV-vis analysis, and inductively
coupled plasma mass spectrometry (ICP-MS). The results indicated that the TEOS/KH
570/MTES/Ag-SiO2 (15:6:1:0.6-1.0) films, which exhibited simple in-solution film
formation on PE ETTs, had a homogeneous morphology, high transmittance above 87%,
high hardness of 5H and strong adhesion to the tubes. The concentration of Ag+
ion dissolved out from the antibacterial coating is very low in ICP-MS results.
The antibacterial test results show that the antibacterial coatings have
excellent antibacterial property with antibacterial ratio up to 93.5% when Ag
SiO2 content is 2.6%. In pyrogen test and hemolytic test, the body temperature of
rabbits rise 0.03 degrees c for 3 h after inserting antibacterial PE ETT, and the
hemolytic ratio is 0.7512%, which conform to the requirements of biomedical
material. The results preliminarily proved that the antibacterial materials could
be a good candidate of medical catheter material application or medical device
surface coating materials. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res
Part B: Appl Biomater, 105B: 91-98, 2017.
PMID- 26426544
TI - Sexual function and depressive symptoms in young women with thyroid autoimmunity
and subclinical hypothyroidism.
AB - OBJECTIVE: The results of few studies conducted to date suggest an increased
prevalence of sexual dysfunction in patients with thyroid disorders. DESIGN: The
aim of this study was to compare female sexual function and depressive symptoms
between women with autoimmune thyroid disease and with mild thyroid failure.
PATIENTS: The study included four groups of young women: euthyroid women with
Hashimoto's thyroiditis (Group 1), women with nonautoimmune subclinical
hypothyroidism (Group 2), women with autoimmune subclinical hypothyroidism (Group
3) and healthy euthyroid females without thyroid autoimmunity (Group 4).
MEASUREMENTS: Beyond measuring serum hormone levels and thyroid antibody titres,
all enrolled women completed questionnaires evaluating female sexual function
(Female Sexual Function Index - FSFI) and the presence and severity of depressive
symptoms (Beck Depression Inventory-Second Edition - BDI-II). RESULTS: The mean
total FSFI score was lower in women with autoimmune hypothyroidism than in the
remaining groups of women, as well as lower in Groups 1 and 2 than in Group 4.
Compared to Group 4, three domains (sexual desire, lubrication and sexual
satisfaction) were lower in Group 1, four domains (desire, arousal, lubrication
and dyspareunia) in Group 2 and all FSFI domain scores in Group 3. The total BDI
II score was higher in Groups 1 and 2 than in Group 4, as well as higher in Group
3 than in the other groups of women. CONCLUSIONS: The obtained results suggest
that both thyroid autoimmunity and mild thyroid failure, particularly if they
occur together, may negatively affect female sexual function and depressive
symptoms.
PMID- 26426545
TI - Synthesis of Triazole-Linked Analogues of c-di-GMP and Their Interactions with
Diguanylate Cyclase.
AB - Cyclic di-GMP (c-di-GMP) is a widespread second messenger that plays a key role
in bacterial biofilm formation. The compound's ability to assume multiple
conformations allows it to interact with a diverse set of target macromolecules.
Here, we analyzed the binding mode of c-di-GMP to the allosteric inhibitory site
(I-site) of diguanylate cyclases (DGCs) and compared it to the conformation
adopted in the catalytic site of the EAL phosphodiesterases (PDEs). An array of
novel molecules has been designed and synthesized by simplifying the native c-di
GMP structure and replacing the charged phosphodiester backbone with an isosteric
nonhydrolyzable 1,2,3-triazole moiety. We developed the first neutral small
molecule able to selectively target DGCs discriminating between the I-site of
DGCs and the active site of PDEs; this molecule represents a novel tool for
mechanistic studies, particularly on those proteins bearing both DGC and PDE
modules, and for future optimization studies to target DGCs in vivo.
PMID- 26426546
TI - Enantioselective sp(3) C-H alkylation of gamma-butyrolactam by a chiral Ir(I)
catalyst for the synthesis of 4-substituted gamma-amino acids.
AB - Ir-catalyzed sp(3) C-H alkylation of gamma-butyrolactam with alkenes was used for
the highly enantioselective synthesis of 5-substituted gamma-lactams, which were
readily converted into chiral 4-substituted gamma-amino acids. A broad scope of
alkenes was amenable as coupling partners, and the alkylated product using
acrylate could be transformed into the key intermediate of pyrrolam A synthesis.
PMID- 26426547
TI - EDUCATION AND IMAGING. Hepatobiliary and Pancreatic: Elastography assessment in
AL hepatic amyloidosis with no fibrosis.
PMID- 26426548
TI - Regarding: Diabetic macular ischaemia is associated with narrower retinal
arterioles in patients with type 2 diabetes.
PMID- 26426549
TI - Editor's message.
PMID- 26426550
TI - Urticaria and angioedema: Diagnostic and treatment considerations.
AB - Urticaria and angioedema are common-and commonly frustrating-problems for
physicians and patients alike. Patients often are in considerable distress with
pruritus and uncomfortable lesions. They are frightened about their condition and
frustrated when modem medicine cannot pinpoint the cause of the symptoms. Both
urticaria and angioedema may be categorized as acute and chronic conditions. The
dividing line between acute and chronic forms is relatively arbitrarily set at 6
weeks. A thorough history and physical examination may provide clues to the
underlying cause, but in the majority of patients, the cause is rarely
identified. One is more likely to discover the cause of acute than of chronic
urticaria. A multitude of laboratory tests can be performed, but they often do
not provide a diagnosis. It is not appropriate to do a large "screening" battery
oflaboratory tests. The dermal mast cells and their mediators playa central role
in chronic urticaria. Chronic urticaria may have an autoimmune aspect. Recent
evidence reveals that 50% of patients with chronic urticaria have a cutaneous
autoimmune disorder mediated by autoantibodies to the high-affinity IgE receptor
on mast cells. Biopsy may be necessary and may help with treatment.
PMID- 26426551
TI - Contact dermatitis: Evaluation and treatment.
AB - Contact dermatitis is a common condition that can be categorized as irritant
dermatitis and allergic contact dermatitis. Although each of these conditions may
have a similar presentation, allergic contact dermatitis is immunologically
mediated, whereas irritant contact dermatitis is not. Contact dermatitis can be
acute, subacute, or chronic, and each of these phases may progress into the next.
Almost any substance may induce a cutaneous reaction, depending on its
concentration, the duration of contact, and the condition of the contacted skin.
It is estimated that there are more than 6 million chemicals in the environment;
approximately 3000 are potential sensitizers. A careful history may identify the
responsible agent. If the contactant is identified and eliminated, the contact
dermatitis can be a self-limited, mild condition. H the exposure is not
discontinued, a cycle of itching, scratching, and skin disruption occurs, which
leads to chronic changes in the skin. The history of presentation, including
occupational exposures, and distribution of the rash are important in identifying
the offending agent. More severe cases may require more extensive evaluation,
possibly including patch testing, to determine the offending agent. This article
reviews treatment, including antihistamines, topical and oral steroids, physical
measures such as cold water compresses, and the treatment of secondary infection.
PMID- 26426552
TI - Skin manifestations of food allergies.
AB - The role of dietary factors in chronic skin diseases has been a subject of
controversy, but several investigators have shown the effectiveness of
elimination diets in the management of some patients with atopic dermatitis.
Chronic skin diseases are common, complex, and often difficult to treat;
therefore, the physician should consider all possible causes. More people
consider themselves to have food allergies than can actually be documented to
have an immunologic reaction to foods. Six foods--egg, peanut, cow's milk, soy,
fish, and wheat-account for most skin reactions to food in children, with egg,
peanut, and cow's milk being most common. Elimination of the offending food can
be an effective form of treatment, but it must be done with caution, and while
ensuring that the patient maintains adequate nutrition.
PMID- 26426553
TI - Skin manifestations of allergic reactions: A 'comparative color atlas'.
PMID- 26426554
TI - CME QUIZ.
PMID- 26426555
TI - Atopic dermatitis: A clinical review for the primary care physician.
AB - Atopic dermatitis is a common disease, causing significant morbidity. The
histology and cellular mechanisms suggest that atopic dermatitis is an atopic
disease similar to asthma and allergic rhinitis, with helper T type 2 lymphocytes
being at least a component of the pathogenesis of the disease. Specific
allergies, including food allergies, should be explored and treated. Treatment
should be directed at increasing the patient's quality of life. Antihistamines,
topical steroids, and lubricants are the keystones of therapy. In severe cases,
oral steroids may be necessary but should be used sparingly. Interferon,
cyclospocine, phototherapy, and immunosuppressive agents may be necessary in
refractory cases. It appears that leukotriene inhibitors may have a future role
in therapy. Clinical assessment and follow-up are important, as other atopic
diseases such as asthma and allergic nasosinus disease may eventually develop in
many of these patients.
PMID- 26426556
TI - Comparison of Chest Compressions Metrics Measured Using the Laerdal Skill
Reporter and Q-CPR: A Simulation Study.
AB - INTRODUCTION: There has been an increased emphasis on the quality of chest
compressions as a part of the cardiopulmonary resuscitation (CPR) bundle of care
for recent times. During CPR training, chest compression quality parameters can
be measured directly from sensors within a manikin or from external devices
placed on the manikin chest that use accelerometer-based technology. The aim of
this study was to compare external chest compression data from the manikin-based
Laerdal Skill Reporter (LSR) and the accelerometer-based Q-CPR technology,
incorporated into the Philips MRx defibrillator, during CPR on a single Resusci
Anne Simulator manikin. METHODS: Each paramedic (n = 15) performed 2 sessions of
2 minutes of chest compressions, with a 2-minute rest period in between sessions.
Both over-the-head and from-the-side positions were used on a single manikin. The
quality of chest compressions were concurrently measured using both LSR and
Philips MRx Q-CPR accelerometer with audiovisual feedback disabled. RESULTS:
There was no significant difference in the measurement of the number of chest
compressions performed in 2 minutes, the compression rate, total number of
compressions of adequate depth, or the number of compressions exhibiting leaning
between the LSR and the Phillips Q-CPR devices. There was a significant
difference in measurement of compression depth (P < 0.0001) and duty cycle (P <
0.0001) with the MRx Q-CPR accelerometer demonstrating both lower compression
depth and duty cycle compared with LSR. CONCLUSIONS: There was no significant
difference in most chest compression quality metrics measured between the LSR and
the Phillips Q-CPR devices when measured on a manikin. However, there were
significant differences in the measurement of duty cycle and also the depth of
compressions between the 2 devices with the Phillips Q-CPR device measuring lower
depth of compression and duty cycle compared with the LSR device.
PMID- 26426557
TI - Clinical Placement Before or After Simulated Learning Environments?: A
Naturalistic Study of Clinical Skills Acquisition Among Early-Stage Paramedicine
Students.
AB - BACKGROUND: There is conflicting evidence surrounding the merit of clinical
placements (CPs) for early-stage health-profession students. Some contend that
early-stage CPs facilitate contextualization of a subsequently learned theory.
Others argue that training in simulated-learning experiences (SLEs) should occur
before CP to ensure that students possess at least basic competency. We sought to
investigate both claims. METHODS: First-year paramedicine students (n = 85)
undertook 3 days of CP and SLEs as part of course requirements. Students
undertook CP either before or after participation in SLEs creating 2 groups (Clin
-> Sim/Sim -> Clin). Clinical skills acquisition was measured via direct scenario
based clinical assessments with expert observers conducted at 4 intervals during
the semester. Perceptions of difficulty of CP and SLE were measured via the
National Aeronautics and Space Administration Task Load Index. RESULTS: Students'
clinical assessment scores in both groups improved significantly from beginning
to end of semester (P < 0.001). However, at semester's end, clinical assessment
scores for the Sim -> Clin group were statistically significantly greater than
those of the Clin -> Sim group (P = 0.021). Both groups found SLEs more demanding
than CP (P < 0.001). However, compared with the Sim -> Clin group, the Clin ->
Sim group rated SLE as substantially more time-demanding than CP (P = 0.003).
CONCLUSIONS: Differences in temporal demand suggest that the Clin -> Sim students
had fewer opportunities to practice clinical skills during CP than the Sim ->
Clin students due to a more limited scope of practice. The Sim -> Clin students
contextualized SLE within subsequent CP resulting in greater improvement in
clinical competency by semester's end in comparison with the Clin -> Sim students
who were forced to contextualize skills retrospectively.
PMID- 26426558
TI - Use of the Learning Curve-Cumulative Summation Test for Leopold Maneuvers
Assessment in a Simulator: A Pilot Study.
AB - INTRODUCTION: Simulation enables medical students to practice clinical skills in
a safe environment. Graduates in medicine must be able to correctly perform an
examination on a pregnant woman using Leopold maneuvers. Learning curves
cumulative summation (LC-CUSUM) may help determine when the student has achieved
a specific skill. Our objective was to perform the LC-CUSUM test regarding the
ability of students to correctly carry out Leopold maneuvers; a pregnancy
simulator was used, transferring the results to a clinical setting. METHODS: Five
medical students were trained to carry out Leopold maneuvers using the simulator.
Each student performed maneuvers for 50 cases of different fetus positions; a LC
CUSUM was plotted for each student. Afterward, the students performed the Leopold
maneuvers on 5 pregnant women. RESULTS: Of the 5 students, 3 achieved a level of
proficiency; the attempts needed for reaching this level were 13, 13, and 37,
respectively. The other 2 students did not reach proficiency level. Of the
students who became successfully proficient with the simulator, one of them
attained a 100% success rate in pregnant patients, whereas the other two had
success rates of 80%. The students who did not achieve a level of competency with
the simulator had only a 60% success rate with patients. CONCLUSIONS: Because of
the differences observed between students in the number of attempts needed for
achieving proficiency in Leopold maneuvers, we believe that each student should
build his/her own learning curve. Achieving competency in carrying out Leopold
maneuvers using the simulator could be transferable to patients.
PMID- 26426559
TI - Defining the Simulation Technician Role: Results of a Survey-Based Study.
AB - INTRODUCTION: In health care simulation, simulation technicians perform multiple
tasks to support various educational offerings. Technician responsibilities and
the tasks that accompany them seem to vary between centers. The objectives were
to identify the range and frequency of tasks that technicians perform and to
determine if there is a correspondence between what technicians do and what they
feel their responsibilities should be. We hypothesized that there is a core set
of responsibilities and tasks for the technician position regardless of
background, experience, and type of simulation center. METHODS: We conducted a
prospective, survey-based study of individuals currently functioning in a
simulation technician role in a simulation center. This survey was designed
internally and piloted within 3 academic simulation centers. Potential
respondents were identified through a national mailing list, and the survey was
distributed electronically during a 3-week period. RESULTS: A survey request was
sent to 280 potential participants, 136 (49%) responded, and 73 met inclusion
criteria. Five core tasks were identified as follows: equipment setup and
breakdown, programming scenarios into software, operation of software during
simulation, audiovisual support for courses, and on-site simulator maintenance.
Independent of background before they were hired, technicians felt unprepared for
their role once taking the position. Formal training was identified as a need;
however, the majority of technicians felt experience over time was the main
contributor toward developing knowledge and skills within their role.
CONCLUSIONS: This study represents a first step in defining the technician role
within simulation-based education and supports the need for the development of a
formal job description to allow recruitment, development, and certification.
PMID- 26426560
TI - Assessing Procedural Competence: Validity Considerations.
AB - STATEMENT: Simulation-based medical education (SBME) offers opportunities for
trainees to learn how to perform procedures and to be assessed in a safe
environment. However, SBME research studies often lack robust evidence to support
the validity of the interpretation of the results obtained from tools used to
assess trainees' skills. The purpose of this paper is to describe how a validity
framework can be applied when reporting and interpreting the results of a
simulation-based assessment of skills related to performing procedures. The
authors discuss various sources of validity evidence because they relate to SBME.
A case study is presented.
PMID- 26426561
TI - Learning Empathy Through Simulation: A Systematic Literature Review.
AB - STATEMENT: Simulation is increasingly used as an educational methodology for
teaching empathy to preservice health professional students. This systematic
review aimed to determine if and how simulation, including games, simulated
patients, and role-play, might develop empathy and empathetic behaviors in
learners. Eleven databases or clearing houses including MEDLINE, EMBASE, CINAHL,
PsychInfo, and ERIC were searched for all articles published from any date until
May 2014, using terms relating to (i) preservice health professional students,
(ii) simulation, and (iii) empathy. Twenty-seven studies met the inclusion
criteria, including 9 randomized controlled trials. A narrative synthesis
suggests that simulation may be an appropriate method to teach empathy to
preservice health professional students and identifies the value of the learner
taking the role of the patient.
PMID- 26426562
TI - Local Anesthetic Systemic Toxicity in a Nonoperative Location.
PMID- 26426563
TI - Acquiring Insight Into the Cognitive Processes of Clinicians.
PMID- 26426564
TI - Eye Tracking to Acquire Insight Into the Cognitive Processes of Clinicians: Is
"Looking" the Same as "Seeing"?
PMID- 26426565
TI - Association Between Multimodality Neck Treatment and Work and Leisure
Impairment: A Disease-Specific Measure to Assess Both Impairment and
Rehabilitation After Neck Dissection.
AB - IMPORTANCE: This study describes the effect of adjuvant treatment on shoulder
related quality of life, leisure activities, and employment for patients
undergoing neck dissection for head and neck cancer. OBJECTIVE: To explore the
association between treatment outcome and shoulder-related on critical daily life
functions such as employment and recreation. DESIGN, SETTING, AND PARTICIPANTS:
Cross-sectional study of patients with head and neck cancer at a tertiary care
hospital. EXPOSURES: Level V-sparing selective neck dissection or modified
radical neck dissection sparing the accessory nerve, with or without radiation
therapy and/or chemotherapy. MAIN OUTCOMES AND MEASURES: Patients completed the
Neck Dissection Impairment Index (NDII), with scores ranging from 0 to 100 and
higher scores indicating better shoulder functioning and shoulder-related quality
of life, and underwent objective testing with the Constant-Murley Shoulder
Function Test (Constant test) at least 12 months after the completion of all
adjuvant treatment. Additional outcome measures related to physical therapy, pain
medication use, leisure activity, and employment status. RESULTS: We evaluated
167 patients who underwent 121 selective neck dissections and 46 modified radical
neck dissections. The median (range) NDII score was 90 (10-100). Patients with
modified radical neck dissection reported lower scores than those with selective
neck dissection (85 [10-100] vs. 92 [30-100]; P = .01). Multivariable analysis
showed that advanced-stage disease (mean, 77 [range, 25-100] vs. 87 [18-100]; P =
.006), radiation therapy (80 [10-100] vs. 88 [50-100]; P = .03), and chemotherapy
(77 [30-100] vs. 83 [18-100]; P = .002) were associated with greater shoulder
impairment. The NDII and Constant test were well correlated (0.64; P < .001).
Change in leisure activity was correlated with greater impairment (median [range]
NDII score, 90 [18-100] for patients with no change vs. 53 [10-100] for patients
with change, P = .005; Constant score, 85 [12-100] vs. 68 [10-88], P = .004).
Patients who remained employed or resumed working had higher median (range) NDII
scores (94 [10-100] and 88 [75-100], respectively) than those who limited or
stopped working (70 [10-100]), which also correlates with greater shoulder
impairment (P < .001). CONCLUSIONS AND RELEVANCE: More aggressive treatment,
either in the form of increased surgical dissection, radiation therapy, or
chemotherapy, was associated with worse shoulder function and quality of life.
The degree of impairment perceived by the patient and measured in objective
testing was correlated with leisure activity and employment status. These
findings may stimulate further investigation related to optimizing quality of
life following neck dissection.
PMID- 26426566
TI - Asystole during Pulse Generator Change: Unexpected Failure of Pacemaker Implant
Autoinitialization.
PMID- 26426567
TI - Mechanism-Based Trapping of the Quinonoid Intermediate by Using the K276R Mutant
of PLP-Dependent 3-Aminobenzoate Synthase PctV in the Biosynthesis of Pactamycin.
AB - Mutational analysis of the pyridoxal 5'-phosphate (PLP)-dependent enzyme PctV was
carried out to elucidate the multi-step reaction mechanism for the formation of 3
aminobenzoate (3-ABA) from 3-dehydroshikimate (3-DSA). Introduction of mutation
K276R led to the accumulation of a quinonoid intermediate with an absorption
maximum at 580 nm after the reaction of pyridoxamine 5'-phosphate (PMP) with 3
DSA. The chemical structure of this intermediate was supported by X-ray
crystallographic analysis of the complex formed between the K276R mutant and the
quinonoid intermediate. These results clearly show that a quinonoid intermediate
is involved in the formation of 3-ABA. They also indicate that Lys276 (in the
active site of PctV) plays multiple roles, including acid/base catalysis during
the dehydration reaction of the quinonoid intermediate.
PMID- 26426568
TI - Long-term outcome of living kidney donation: Position paper of the European
Committee on Organ Transplantation (CD-P-TO), Council of Europe.
PMID- 26426569
TI - Room-Temperature Oxidation of Formaldehyde by Layered Manganese Oxide: Effect of
Water.
AB - Layered manganese oxide, i.e., birnessite was prepared via the reaction of
potassium permanganate with ammonium oxalate. The water content in the birnessite
was adjusted by drying/calcining the samples at various temperatures (30 degrees
C, 100 degrees C, 200 degrees C, 300 degrees C, and 500 degrees C).
Thermogravimetry-mass spectroscopy showed three types of water released from
birnessite, which can be ascribed to physically adsorbed H2O, interlayer H2O and
hydroxyl, respectively. The activity of birnessite for formaldehyde oxidation was
positively associated with its water content, i.e., the higher the water content,
the better activity it has. In-situ DRIFTS and step scanning XRD analysis
indicate that adsorbed formaldehyde, which is promoted by bonded water via
hydrogen bonding, is transformed into formate and carbonate with the consumption
of hydroxyl and bonded water. Both bonded water and water in air can compensate
the consumed hydroxyl groups to sustain the mineralization of formaldehyde at
room temperature. In addition, water in air stimulates the desorption of
carbonate via water competitive adsorption, and accordingly the birnessite
recovers its activity. This investigation elucidated the role of water in
oxidizing formaldehyde by layered manganese oxides at room temperature, which may
be helpful for the development of more efficient materials.
PMID- 26426570
TI - Evidence of cancer-promoting roles for AMPK and related kinases.
AB - The discovery that the 5'AMP-activated protein kinase (AMPK) serves to link the
tumour suppressors LKB1 and the tuberous sclerosis complex and functions to slow
macromolecular synthesis through attenuation of the mechanistic target of
rapamycin complex 1 revealed a role for AMPK in tumour suppression. On the other
hand, the well-recognized role of AMPK in maintaining ATP homeostasis, through
suppression of anabolism and promotion of catabolism, as well as the role of AMPK
in neutralizing reactive oxygen species, via maintenance of NADPH-dependent
reductive capacity, point to tumour-protective roles in the context of metabolic
stress, which is a key feature of many solid tumours. A growing number of studies
thus suggest a duality of functions for AMPK that are either pro- or anti-cancer,
depending upon context. Importantly, AMPK is composed of three subunits, and
multiple isoforms exist for all three, allowing for different permutations to
assemble and the potential for specific AMPK complexes to regulate distinct
cellular processes. Moreover, certain subunits of the AMPK complex are frequently
overexpressed in a spectrum of human cancer types, suggesting an outright
oncogenic function for specific AMPK complexes. Adding complexity to this
picture, the catalytic AMPK alpha subunits belong to a family of 14 kinases that
can all be activated by LKB1 and studies are beginning to reveal a similar
duality of roles in cancer for other members of the AMPK-related kinase family.
PMID- 26426571
TI - anti-Selective aminofluorination of alkenes with amidines mediated by hypervalent
iodine(iii) reagents.
AB - anti-Selective aminofluorination of alkenes with amidines was enabled by
hypervalent iodine(iii) reagents, affording 4-fluoroalkyl-2-imidazolines. Further
reductive ring-opening of the 2-imidazoline moiety could deliver highly
functionalized 3-fluoropropane-1,2-diamine derivatives.
PMID- 26426572
TI - The use of the Rx spin label in orientation measurement on proteins, by EPR.
AB - The bipedal spin label Rx is more restricted in its conformation and dynamics
than its monopodal counterpart R1. To systematically investigate the utility of
the Rx label, we have attempted to comprehensively survey the attachment of Rx to
protein secondary structures. We have examined the formation, structure and
dynamics of the spin label in relation to the underlying protein in order to
determine feasibility and optimum conditions for distance and orientation
measurement by pulsed EPR. The labeled proteins have been studied using molecular
dynamics, CW EPR, pulsed EPR distance measurement at X-band and orientation
measurement at W-band. The utility of different modes and positions of attachment
have been compared and contrasted.
PMID- 26426574
TI - Is pholcodine a dangerous cough suppressant?
PMID- 26426573
TI - Gonadotropin-Releasing Hormone Agonists for Ovarian Function Preservation in
Premenopausal Women Undergoing Chemotherapy for Early-Stage Breast Cancer: A
Systematic Review and Meta-analysis.
AB - IMPORTANCE: Chemotherapy may result in a detrimental effect on ovarian function
and fertility in premenopausal women undergoing treatment for early-stage breast
cancer (EBC). To minimize risk of harm to ovarian function and fertility for
patients in this setting, careful considerations should be made. Gonadotropin
releasing hormone agonists (GnRHa) have been suggested as an alternative to
prevent the loss of ovarian function due to exposure to cytotoxic agents, but
GnRHa use for ovarian protection in EBC patients is not fully resolved.
OBJECTIVE: To determine the effectiveness of GnRHa administered concurrently with
chemotherapy for ovarian function preservation. DATA SOURCES: PubMed, SCOPUS, and
Cochrane databases were searched for studies published between January 1975 and
March 2015. The abstracts of the American Society of Clinical Oncology Annual
Meeting between 1995 and 2014 and the San Antonio Breast Cancer Symposium between
2009 and 2014 were searched as well. STUDY SELECTION: Prospective, randomized,
clinical trials addressing the role of ovarian suppression with GnRHa in
preventing early ovarian dysfunction in premenopausal women undergoing treatment
for EBC were selected. DATA EXTRACTION AND SYNTHESIS: Data extraction was
performed independently by 2 authors. The methodology and the risk of bias were
assessment based on the description of randomization method, withdrawals, and
blinding process. MAIN OUTCOMES AND MEASURES: Rate of resumption of regular
menses after a minimal follow-up period of 6 months following chemotherapy was
used as a surrogate to assess the incidence of ovarian dysfunction. Additional
secondary outcomes included hormone levels and number of pregnancies. Risk ratio
estimates were calculated based on the number of evaluable patients. Analyses
were conducted using a random effect model. RESULTS: Seven studies were included
in this analysis, totaling 1047 randomized patients and 856 evaluable patients.
The use of GnRHa was associated with a higher rate of recovery of regular menses
after 6 months (odds ratio [OR], 2.41; 95% CI, 1.40-4.15; P = .002) and at least
12 months (OR, 1.85; 95% CI, 1.33-2.59; P < .001) following the last chemotherapy
cycle. The use of GnRHa was also associated with a higher number of pregnancies
(OR, 1.85; 95% CI, 1.02-3.36; P = .04), although this outcome was not uniformly
reported and fertility or rate of pregnancy was not the primary outcome in any of
the trials. CONCLUSIONS AND RELEVANCE: Gonadotropin-releasing hormone agonists
given with chemotherapy was associated with increased rates of recovery of
regular menses in this meta-analysis. Evidence was insufficient to assess
outcomes related to GnRHa and ovarian function and fertility and needs further
investigation.
PMID- 26426576
TI - Comparison of efficacy and safety of lateral-to-medial continuous transversus
abdominis plane block with thoracic epidural analgesia in patients undergoing
abdominal surgery: A randomised, open-label feasibility study.
AB - BACKGROUND: We recently described a lateral-to-medial approach for transversus
abdominis plane (LM-TAP) block, which may permit preoperative initiation of the
block. OBJECTIVE: Our objective was to evaluate the feasibility of continuous LM
TAP blocks in clinical practice in comparison with thoracic epidural analgesia
(TEA). DESIGN: A randomised, open-label study. SETTING: University Hospital,
London Health Sciences Centre, London, Ontario, Canada from July 2008 to August
2012. PATIENTS: Fifty adult patients undergoing open abdominal surgery via
laparotomy were allocated randomly to receive preoperative catheter-congruent TEA
or ultrasound-guided continuous bilateral LM-TAP block for 72 h postoperatively.
Reasons for noninclusion were American Society of Anesthesiologists' physical
status more than 4, known allergy to study drugs, chronic pain/opioid dependence,
spinal abnormalities or psychiatric illness. INTERVENTIONS: In the TEA group (n =
24), patient-controlled epidural analgesia was maintained using bupivacaine 0.1%
with hydromorphone 10 MUg ml-1 after establishment of the initial block. In the
LM-TAP group (n = 26), ultrasound-guided LM-TAP catheters were inserted on each
side preoperatively after a bolus of 30 ml of ropivacaine 0.5% (20 ml subcostal
and 10 ml subumbilical injections on both sides). Analgesia was maintained with
an infusion of ropivacaine 0.35% at a rate of 2 to 2.5 ml h-1 through each
catheter, along with rescue intravenous patient-controlled analgesia. MAIN
OUTCOME MEASURES: The primary outcome was pain score on coughing 24 h after the
end of surgery. Secondary outcomes were pain scores from 24 to 72 h,
intraoperative and postoperative opioid consumption, time to onset of bowel
movement and side effect profiles. RESULTS: Mean [95% confidence interval (95%
CI)] pain scores at rest ranged from 1. 7 (0.9 to 2.5) to 2.3 (1.1 to 3.4) in TEA
vs. 1.5 (0.7 to 2.2) to 2.2 (1.3 to 3.0) in LM-TAP (P = 0.829). The dynamic pain
scores ranged from 2.9 (1.5 to 4.4) to 3.8 (2.8 to 4.8) in TEA vs. 3.3 (2.4 to
4.3) to 3.8 (2.7 to 4.9) in LM-TAP (P = 0.551). The variability in pain scores
was lower in the LM-TAP group than in the TEA group in the first 24 h
postoperatively. Patient satisfaction and other secondary outcomes were similar.
CONCLUSION: Continuous bilateral LM-TAP block can be initiated preoperatively and
may provide comparable analgesia to TEA in patients undergoing laparotomy.
CLINICAL TRIALS REGISTRY: not registered because registration was not mandatory
at the time of starting the trial.
PMID- 26426575
TI - The Shamrock lumbar plexus block: A dose-finding study.
AB - BACKGROUND: The Shamrock technique is a new method for ultrasound-guided lumbar
plexus blockade. Data on the optimal local anaesthetic dose are not available.
OBJECTIVE: The objective of this study is to estimate the effective dose of
ropivacaine 0.5% for a Shamrock lumbar plexus block. DESIGN: A prospective dose
finding study using Dixon's up-and-down sequential method. SETTING: University
Hospital Orthopaedic Anaesthesia Unit. INTERVENTION: Shamrock lumbar plexus block
performance and block assessment were scheduled preoperatively. Ropivacaine 0.5%
was titrated with the Dixon and Massey up-and-down method using a stepwise change
of 5 ml in each consecutive patient. Combined blocks of the femoral, the lateral
femoral cutaneous and the obturator nerve were prerequisite for a successful
lumbar plexus block. PATIENTS: Thirty patients scheduled for lower limb
orthopaedic surgery completed the study. MAIN OUTCOME MEASURES: The minimum
effective anaesthetic volume of ropivacaine 0.5% (ED50) to achieve a successful
Shamrock lumbar plexus block in 50% of the patients. Further analysis of the data
was performed with a logistic regression model to calculate ED95 and to estimate
the effective doses for a sensory lumbar plexus block not requiring a motor block
of the femoral nerve. RESULTS: The Dixon and Massay estimate of the ED50 was 20.4
[95% confidence interval (95% CI) 13.9 to 30.0] ml ropivacaine 0.5%. The logistic
regression estimate of the ED95 was 36.0 (95% CI 19.7 to 52.2) ml ropivacaine
0.5%. For a sensory lumbar plexus block, the ED50 was 17.1 (95% CI 12.3 to 21.9)
ml and the ED95 was 25.8 (95% CI 18.6 to 33.1) ml. CONCLUSION: A volume of 20.4
ml ropivacaine 0.5% provided a successful Shamrock lumbar plexus block in 50% of
the patients. A volume of 36.0 ml would be successful in 95% of the patients.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01956617.
PMID- 26426578
TI - Correction: Registered report: A coding-independent function of gene and
pseudogene mRNAs regulates tumour biology.
PMID- 26426577
TI - Clonidine versus sufentanil as an adjuvant to ropivacaine in patient-controlled
epidural labour analgesia: A randomised double-blind trial.
AB - BACKGROUND: Adjuvants to local anaesthetics for epidural labour analgesia are
useful if they reduce side-effects or personnel requirements. Epidural clonidine
improves analgesia and provides a significant local anaesthetic-sparing effect.
OBJECTIVE: To compare the number of rescue doses administered by the
anaesthesiologist when clonidine or sufentanil is added to epidural ropivacaine.
DESIGN: A randomised double-blind trial. SETTING: Cliniques Universitaires Saint
Luc, Universite Catholique de Louvain, Brussels, Belgium, from June 2009 to June
2010. PATIENTS: One hundred and ninety-five women in labour. INTERVENTION:
Epidural analgesia initiated with 10 ml ropivacaine 0.1%, women randomised to
receive patient-controlled epidural analgesia (5 ml demand bolus, 15 min lockout)
with ropivacaine 0.1% and sufentanil 0.25 MUg ml-1 (RS group; n = 65), or
ropivacaine 0.1% and clonidine 1.5 MUg ml-1 (RC1.5 group; n = 65) or ropivacaine
0.1% and clonidine 3 MUg ml-1 (RC3 group; n = 65). Rescue analgesia was available
as needed - 10 ml ropivacaine 0.1% (numerical rating scale <6/10) or ropivacaine
0.2% (numerical rating scale >=6/10). MAIN OUTCOME: Comparison of the total
number of rescue doses. RESULTS: The total number of rescue doses was similar
among the groups [median (interquartile range): 1 (0 to 1) in the RC1.5 group, 1
(1 to 2) in the RC3 group and 2 (1 to 2) in the RS group; overall P = 0.056].
However, fewer patients in both the RC1.5 and RC3 groups needed two or more
rescue doses (25 and 29% versus 52% in the RS group, P = 0.01). The rate of
instrumental delivery was higher in both clonidine groups (13 and 12% versus 0%,
P = 0.03). Nausea was significantly less frequent in both the clonidine groups.
Satisfaction scores, total ropivacaine consumption, maternal sedation, and
hypotension and neonatal outcomes were similar among the groups. CONCLUSION:
Compared with sufentanil 0.25 MUg ml-1, addition of clonidine (1.5 to 3 MUg ml-1)
to patient-controlled epidural analgesia with ropivacaine 0.1% provided similar
labour analgesia and a similar need for anaesthesiologist-administered rescue
doses. Clonidine 3 MUg ml-1 did not offer any advantage over clonidine 1.5 MUg ml
1. The instrumentation rate was higher in both the clonidine groups.
PMID- 26426579
TI - On spinning plates.
PMID- 26426581
TI - Room-temperature, solution-processable organic electron extraction layer for high
performance planar heterojunction perovskite solar cells.
AB - In this work, we describe a room-temperature, solution-processable organic
electron extraction layer (EEL) for high-performance planar heterojunction
perovskite solar cells (PHJ PVSCs). This EEL is composed of a bilayered
fulleropyrrolidinium iodide (FPI)-polyethyleneimine (PEIE) and PC61BM, which
yields a promising power conversion efficiency (PCE) of 15.7% with insignificant
hysteresis. We reveal that PC61BM can serve as a surface modifier of FPI-PEIE to
simultaneously facilitate the crystallization of perovskite and the charge
extraction at FPI-PEIE/CH3NH3PbI3 interface. Furthermore, the FPI-PEIE can also
tune the work function of ITO and dope PC61BM to promote the efficient electron
transport between ITO and PC61BM. Based on the advantages of room-temperature
processability and decent electrical property of FPI-PEIE/PC61BM EEL, a high
performance flexible PVSC with a PCE ~10% is eventually demonstrated. This study
shows the potential of low-temperature processed organic EEL to replace
transition metal oxide-based interlayers for highly printing compatible PVSCs
with high-performance.
PMID- 26426580
TI - Lack of PRKD2 and PRKD3 kinase domain somatic mutations in PRKD1 wild-type
classic polymorphous low-grade adenocarcinomas of the salivary gland.
AB - AIMS: Polymorphous low-grade adenocarcinoma (PLGA) is the second most common
intra-oral salivary gland malignancy. The vast majority of PLGAs harbour a PRKD1
E710D hot-spot somatic mutation or somatic rearrangements of PRKD1, PRKD2 or
PRKD3. Given the kinase domain homology among PRKD1, PRKD2 and PRKD3, we sought
to define whether PLGAs lacking PRKD1 somatic mutations or PRKD gene family
rearrangements would be driven by somatic mutations affecting the kinase domains
of PRKD2 or PRKD3. METHODS AND RESULTS: DNA was extracted from eight
microdissected PLGAs lacking PRKD1 somatic mutations or PRKD gene family
rearrangements. Samples were thoroughly centrally reviewed, microdissected and
subjected to Sanger sequencing of the kinase domains of the PRKD2 and PRKD3
genes. None of the PLGAs lacking PRKD1 somatic mutations or PRKD gene family
rearrangements harboured somatic mutations in the kinase domains of the PRKD2 or
PRKD3 genes. CONCLUSION: PLGAs lacking PRKD1 somatic mutations or PRKD gene
family rearrangements are unlikely to harbour somatic mutations in the kinase
domains of PRKD2 or PRKD3. Further studies are warranted to define the driver
genetic events in this subgroup of PLGAs.
PMID- 26426583
TI - Increased Risk of Post-Trauma Stroke after Traumatic Brain Injury-Induced Acute
Respiratory Distress Syndrome.
AB - This study determines whether acute respiratory distress syndrome (ARDS) is an
independent risk factor for an increased risk of post-traumatic brain injury
(TBI) stroke during 3-month, 1-year, and 5-year follow-ups, respectively, after
adjusting for other covariates. Clinical data for the analysis were from the
National Health Insurance Database 2000, which covered a total of 2121 TBI
patients and 101 patients with a diagnosis of TBI complicated with ARDS (TBI
ARDS) hospitalized between January 1, 2001 and December 31, 2005. Each patient
was tracked for 5 years to record stroke occurrences after discharge from the
hospital. The prognostic value of TBI-ARDS was evaluated using a multivariate Cox
proportional hazard model. The main outcome found that stroke occurred in nearly
40% of patients with TBI-ARDS, and the hazard ratio for post-TBI stroke increased
fourfold during the 5-year follow-up period after adjusting for other covariates.
The increased risk of hemorrhagic stroke in the ARDS group was considerably
higher than in the TBI-only cohort. This is the first study to report that post
traumatic ARDS yielded an approximate fourfold increased risk of stroke in TBI
only patients. We suggest intensive and appropriate medical management and
intensive follow-up of TBI-ARDS patients during the beginning of the hospital
discharge.
PMID- 26426582
TI - Prion Protein Does Not Confer Resistance to Hippocampus-Derived Zpl Cells against
the Toxic Effects of Cu2+, Mn2+, Zn2+ and Co2+ Not Supporting a General
Protective Role for PrP in Transition Metal Induced Toxicity.
AB - The interactions of transition metals with the prion protein (PrP) are well
documented and characterized, however, there is no consensus on their role in
either the physiology of PrP or PrP-related neurodegenerative disorders. PrP has
been reported to protect cells from the toxic stimuli of metals. By employing a
cell viability assay, we examined the effects of various concentrations of Cu2+,
Zn2+, Mn2+, and Co2+ on Zpl (Prnp-/-) and ZW (Prnp+/+) hippocampus-derived mouse
neuronal cells. Prnp-/- Zpl cells were more sensitive to all four metals than PrP
expressing Zw cells. However, when we introduced PrP or only the empty vector
into Zpl cells, we could not discern any protective effect associated with the
presence of PrP. This observation was further corroborated when assessing the
toxic effect of metals by propidium-iodide staining and fluorescence activated
cell sorting analysis. Thus, our results on this mouse cell culture model do not
seem to support a strong protective role for PrP against transition metal
toxicity and also emphasize the necessity of extreme care when comparing cells
derived from PrP knock-out and wild type mice.
PMID- 26426584
TI - Earth-abundant NiS co-catalyst modified metal-free mpg-C3N4/CNT nanocomposites
for highly efficient visible-light photocatalytic H2 evolution.
AB - In the present work, the earth-abundant NiS co-catalyst modified mesoporous
graphite-like C3N4 (mpg-C3N4)/CNT nanocomposites were prepared via a two-step
strategy: the sol-gel method and the direct precipitation process. The mpg
C3N4/CNT/NiS composite photocatalysts were characterized by X-ray diffraction
(XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy
(XPS), UV-vis absorption spectroscopy, photoluminescence spectroscopy (PL),
photoelectrochemical (PEC) and electrochemical impedance spectra (EIS)
experiments. The photocatalytic H2-production activity over the composite
catalysts was also evaluated by using an aqueous solution containing
triethanolamine under visible light (lambda>= 420 nm). The results showed that
the loading of earth-abundant NiS co-catalysts onto metal-free mpg-C3N4/CNT
nanocomposites can remarkably enhance their photocatalytic H2-production
activity. The optimal loading amount of NiS on metal-free mpg-C3N4/CNT
nanocomposites was about 1 wt%. The as-obtained mpg-C3N4/CNT/1% NiS ternary
composite photocatalyst exhibits the best H2-evolution activity with the highest
rate of about 521 MUmol g(-1) h(-1) under visible light (lambda>= 420 nm), which
is almost 148 times that of a pure mpg-C3N4/CNT sample. The enhanced
photocatalytic activity can be mainly attributed to the synergistic effect of
effectively promoted separation of photo-generated electron-hole pairs and
enhanced H2-evolution kinetics. The co-loading of nanocarbon materials and earth
abundant co-catalysts onto metal-free mpg-C3N4 photocatalysts offers great
potential for practical applications in photocatalytic H2 evolution under visible
light illumination.
PMID- 26426585
TI - Controlled DNA Patterning by Chemical Lift-Off Lithography: Matrix Matters.
AB - Nucleotide arrays require controlled surface densities and minimal nucleotide
substrate interactions to enable highly specific and efficient recognition by
corresponding targets. We investigated chemical lift-off lithography with
hydroxyl- and oligo(ethylene glycol)-terminated alkanethiol self-assembled
monolayers as a means to produce substrates optimized for tethered DNA insertion
into post-lift-off regions. Residual alkanethiols in the patterned regions after
lift-off lithography enabled the formation of patterned DNA monolayers that
favored hybridization with target DNA. Nucleotide densities were tunable by
altering surface chemistries and alkanethiol ratios prior to lift-off.
Lithography-induced conformational changes in oligo(ethylene glycol)-terminated
monolayers hindered nucleotide insertion but could be used to advantage via mixed
monolayers or double-lift-off lithography. Compared to thiolated DNA self
assembly alone or with alkanethiol backfilling, preparation of functional
nucleotide arrays by chemical lift-off lithography enables superior hybridization
efficiency and tunability.
PMID- 26426586
TI - Application of Genomic Technologies in Clinical Pharmacology Research.
AB - Technology is the basis of scientific progress and is an essential component for
continued competitiveness in industry. The development of a new drug candidate is
a long and expensive process, in which a molecule undergoes several stages of
research (both pre-clinical and clinical) before being approved for
commercialization. Scientific progress has revolutionized the pharmaceutical
industry and reshaped the processes by which new drugs are discovered,
investigated, and developed. Currently, the influence of genomic variations in
drug metabolism must be better understood to predict an individual's response to
a given treatment. Employing genomics tools, an individual's genetic profile may
be obtained and used as the basis for prescription of the best treatment option,
thus personalizing medicine. In this review, we discuss how current mainstream
genomic technologies used in clinical pharmacology research can accelerate the
identification of populations that can benefit the most while reducing adverse
events.
PMID- 26426587
TI - Economic Evaluation of the Use of Drug-Eluting Stents versus Bare-Metal Stents in
Adults with Ischemic Cardiomyopathy Requiring Angioplasty.
AB - BACKGROUND: The value of drug-eluting stents in preventing cardiovascular events
has not been investigated in Mexico. OBJECTIVE: To conduct a cost-effectiveness
analysis of early and new-generation drug-eluting stents from the perspective of
a healthcare provider. METHODS: We conducted a cost-effectiveness analysis of
early and new-generation drug-eluting stents in patients with ischemic
cardiomyopathy attending a Cardiology Hospital of the Mexican Social Security
Institute. The health endpoint used was major acute cardiovascular events
prevented. The effectiveness by stent type was obtained from the literature. A
retrospective chart review study was conducted to collect cost data on
cardiovascular events including seven cost categories. Average and incremental
cost-effectiveness ratios were estimated. Deterministic and probabilistic
sensitivity analyses were performed to test the robustness of estimates. RESULTS:
Incremental cost-effectiveness ratios in base-case were 28,910 and US$ 35,590 for
early and new-generation stents, respectively. In an optimal scenario,
incremental-cost effectiveness ratio was 24,776 and US$ 25,262 for early and new
stents, respectively. Probabilistic sensitivity analysis suggested that 90% of
cases were cost-effective when willingness-to-pay was 58,000 and US$ 66,000 for
early and new-generation stents, respectively. CONCLUSIONS: The cost
effectiveness ratios of early and new-generation stents were significantly higher
than corresponding bare-metal stents.
PMID- 26426588
TI - Proton Magnetic Resonance Spectroscopy Changes in Parkinson's Disease With and
Without Psychosis.
AB - BACKGROUND: Psychosis prevalence in Parkinson's disease is estimated at 8-30%.
Proton magnetic resonance spectroscopy measures specific metabolites as markers
of cell functioning. OBJECTIVE: To study N-acetyl-aspartate and glutamate levels
in the caudate and putamen nuclei in subjects with Parkinson's disease with and
without psychosis. METHODS: We included 20 non-demented Parkinson's disease
patients with psychosis and 20 Parkinson's disease patients without psychosis
matched for age, sex, disease duration, and levodopa equivalent daily dose, all
attended at an academic medical center. Proton magnetic resonance spectroscopy
scans were performed in a 3T GE whole-body scanner. RESULTS: Decreased glutamate
levels scaled to creatine were found in the dorsal caudate (p = 0.005) and
putamen (p = 0.007) of the Parkinson's disease psychosis group compared with the
without psychosis group. Glutamate plus glutamine levels scaled to creatine and N
acetyl-aspartate levels scaled to creatine were also significantly reduced in the
dorsal caudate of the Parkinson's disease with psychosis group (p = 0.018 and p =
0.011, respectively). No group differences were found for any of the other
metabolites in the two regions of interest. CONCLUSIONS: Our findings suggest
that decreased metabolite levels in specific brain areas may be implicated in the
development of psychosis in Parkinson's disease.
PMID- 26426590
TI - Carotid Intima-Media Thickness, Ankle-Arm Index, and Inflammation Profile in
Mexican Patients with Early and Late Onset Type 2 Diabetes.
AB - BACKGROUND: Type 2 diabetes is strongly linked to an increased incidence of
cardiovascular outcomes. Carotid artery intima-media thickness and ankle-arm
index are non-invasive complementary measures as subclinical markers of
atherosclerosis. OBJECTIVE: To evaluate the association of carotid intima-media
thickness, ankle-arm index, and inflammation profile in Mexican patients with
early- and late-onset type 2 diabetes mellitus. MATERIAL AND METHODS: We included
145 subjects at an academic medical center: 77 patients with early-onset (< 40
years of age) and 33 patients with late-onset (>= 40 years) type 2 diabetes
mellitus, and 35 healthy volunteers. Clinical history, anthropometrics, blood
chemistry, lipids profile, glycosylated hemoglobin A1c, cytokines, and high
sensitivity C-reactive protein were determined; carotid and lower limb ultrasound
were taken. Groups were compared with ANOVA or Kruskal-Wallis, Student's t or
Mann-Whitney U. Spearman or Pearson correlation and logistic regression analysis
were used. RESULTS: There were anthropometric and biochemical differences between
the three groups. Concentrations of interleukin-1beta, -4 and -6 were
significantly higher in patients with late versus early onset diabetes. There
were differences in carotid intima-media thickness and ankle-arm index between
early and late onset. Age, body mass index, high-density lipoprotein cholesterol,
high-sensitivity C-reactive protein, waist circumference, and glycosylated
hemoglobin A1c showed direct correlation with carotid intima-media thickness,
while ankle-arm index showed inverse correlation with blood pressure,
glycosylated hemoglobin A1c, time with disease, age at onset, triglycerides, and
fibrinogen. Multivariate analysis showed an association between carotid intima
media thickness and disease duration; ankle-arm index with disease duration and
high-sensitivity C-reactive protein; while only body mass index associated with
end diastolic flow velocity. CONCLUSIONS: Our findings suggest that carotid
intima-media thickness and ankle-arm index are associated with inflammation
markers and could be included in the evaluation of type 2 diabetes mellitus
patients, according to disease onset and duration. There are important
differences in interleukin concentrations between early- and late-onset type 2
diabetes mellitus. Additionally, measurement of high-sensitivity C-reactive
protein is suggested in patients with abnormal ankle-arm index.
PMID- 26426589
TI - Surveillance of Oseltamivir-Resistant Influenza A(H1N1)pdm09 in Guanajuato State,
Mexico from 2009 to 2012.
AB - BACKGROUND: The influenza A(H1N1)pdm09 virus was first identified in Mexico in
April 2009, subsequently spreading worldwide. Soon after the WHO declared a
pandemic, a series of cases involving oseltamivir-resistant viruses were
described, following concerns about the spread of strains resistant to
neuraminidase inhibitors that could hamper control measures. To study the
prevalence of oseltamivir-resistant influenza A(H1N1)pdm09, we implemented a
surveillance program across the state of Guanajuato, Mexico. METHODS: We
collected respiratory samples from patients with confirmed infection with
influenza A(H1N1)pdm09 virus between 2009 and 2012 in rural and urban regions in
Guanajuato, Mexico. Specimens were screened for the H275Y mutation by Sanger
sequencing. RESULTS: A total of 1,192 laboratory confirmed influenza A(H1N1)pdm09
positive samples were processed between 2009 and 2012. Using two endpoint real
time polymerase chain reaction, 575 samples were sequenced. Two different
clusters, I and II, were identified. The H275Y substitution was found in only one
sample from cluster I. CONCLUSIONS: The prevalence of oseltamivir-resistant
influenza A(H1N1)pdm09 2009 viruses during the pandemic period and following
years was very low in our State.
PMID- 26426591
TI - Parecoxib Increases Blood Pressure Through Inhibition of Cyclooxygenase-2
Messenger RNA in an Experimental Model.
AB - BACKGROUND: Cyclooxygenase-2 selective inhibitors have been developed to
alleviate pain and inflammation; however, the use of a selective cyclooxygenase-2
inhibitor is associated with mild edema, hypertension, and cardiovascular risk.
AIM: To evaluate, in an experimental model in normotensive rats, the effect of
treatment with parecoxib in comparison with diclofenac and aspirin and L-NAME, a
non-selective nitric oxide synthetase, on mean arterial blood pressure, and
cyclooxygenase-1 and -2 messenger RNA and protein expression in aortic tissue.
METHODS: Rats were treated for seven days with parecoxib (10 mg/kg/day),
diclofenac (3.2 mg/kg/day), aspirin (10 mg/kg/day), or L-NAME (10 mg/kg/day).
Mean arterial blood pressure was evaluated in rat tail; cyclooxygenase-1 and -2
were evaluated by reverse transcription-polymerase chain reaction and Western
blot analysis in aortic tissue. RESULTS: Parecoxib and L-NAME, but not aspirin
and diclofenac, increased mean arterial blood pressure by about 50% (p < 0.05)
without changes in cardiac frequency. Messenger RNA cyclooxygenase-1 expression
in aortic tissue was not modified with any drug (p < 0.05). L-NAME and parecoxib
treatment decreased messenger RNA cyclooxygenase-2 and cyclooxygenase-2 (p <
0.05). While cyclooxygenase-1 protein decreased with the three drugs tested but
not with L-NAME (p < 0.05), the cyclooxygenase-2 protein decreased only with
aspirin and parecoxib (p < 0.05). CONCLUSION: Parecoxib increases the blood
pressure of normotensive rats by the suppression of COX-2 gene expression, which
apparently induced cardiovascular control.
PMID- 26426592
TI - Diagnostic Value of the Morphometric Model and Adjusted Neck Circumference in
Adults with Obstructive Sleep Apnea Syndrome.
AB - BACKGROUND: Obstructive sleep apnea syndrome is a major public health problem.
The morphometric model and the Sleep Apnea Clinical Score are widely used to
evaluate adults; however, neither of these tools has been validated in a Mexican
population. OBJECTIVE: To determine the diagnostic value of the morphometric
model and the Sleep Apnea Clinical Score and compare them with conventional
clinical instruments. METHODS: A total of 97 individuals were recruited
prospectively. Initial screening excluded 36, of whom nine were subjects without
apnea; the remaining 52 were consecutive patients with obstructive sleep apnea
syndrome diagnosed by nocturnal polysomnography. Diagnostic values of each test
were calculated. RESULTS: Obstructive sleep apnea syndrome patients had
significantly higher scores with both instruments than controls: morphometric
model: 61.3 (95% CI: 45.5-75.3) vs. 41.0 (95% CI: 35.6-45.6); Sleep Apnea
Clinical Score: 45.3 (95% CI: 39.5-40.3) vs. 36 (95% CI: 34.0-36.5),
respectively. For severe cases, the best cutoff point for morphometric model was
46, with a sensitivity of 81% (95% CI: 62.5-92.6) and specificity of 46.7% (95%
CI: 66.4-100), while for Sleep Apnea Clinical Score it was > 48, with a
sensitivity of 61% (95% CI: 46.1-74.2) and specificity of 80.4% (95% CI: 66
90.6). CONCLUSIONS: A morphometric model value of >= 46 or an adjusted neck
circumference (Sleep Apnea Clinical Score) > 48 were adequate for diagnosing
obstructive sleep apnea syndrome.
PMID- 26426593
TI - Albuminuria and Glomerular Filtration Rate in Individuals with Type 1 Diabetes
Mellitus: Contribution of Metabolic Syndrome.
AB - BACKGROUND: The development of metabolic syndrome has been described in patients
with type 1 diabetes mellitus as the disease progresses over time. The purpose of
this study is to assess the relationship between metabolic syndrome, albuminuria,
and glomerular filtration rate, as well as to determine the prevalence of
metabolic syndrome, in a group of Mexican patients with type 1 diabetes mellitus.
METHODS: We conducted a cross-sectional study that included patients with type 1
diabetes mellitus who were diagnosed over 10 years ago and who are seen at the
Diabetes Intensive Control Clinic of the Instituto Nacional de Ciencias Medicas y
Nutricion Salvador Zubiran in Mexico City. The presence of metabolic syndrome was
determined by using the National Cholesterol Education Program-Adult Treatment
Panel III (ATP III) criteria. RESULTS: A total of 81 individuals were studied.
The prevalence of metabolic syndrome was 18.5% (n = 15). A higher albuminuria was
found in subjects with metabolic syndrome (34.9 mg/24 hours; 8.3-169.3) than in
those without metabolic syndrome (9.0 mg/24 hours; 5.0-27.0; p = 0.02).
Glomerular filtration rate was lower in patients with metabolic syndrome (95.3
ml/minute; [64.9-107.2] vs. 110.2 ml/minute [88.1-120.3]; p = 0.04). After
classifying the population according to the number of metabolic syndrome
criteria, a progressive increase in albuminuria and a progressive decrease in
glomerular filtration rate were found with each additional metabolic syndrome
criterion (p = 0.008 and p = 0.032, respectively). After adjusting for age, time
from diagnosis, systolic blood pressure, triglycerides, HDL-cholesterol, and
treatment with angiotensin receptor blockers or angiotensin converting enzyme
inhibitors, we found that age, time from diagnosis, triglycerides, and HDL
cholesterol were independent factors associated with glomerular filtration rate
(R2 = 0.286; p < 0.001). CONCLUSIONS: Metabolic syndrome was associated with a
higher albuminuria and a reduction in glomerular filtration rate in patients with
type 1 diabetes mellitus. Metabolic syndrome was present in 18.5% of this group
of Mexican individuals with type 1 diabetes mellitus.
PMID- 26426594
TI - Lactic Acidosis Complicating Metformin and Non-Nucleoside Reverse Transcriptase
Inhibitor Combination Therapy: A Smoldering Threat in the Post-HAART Era.
AB - Dear Editor, The prevalence of type 2 diabetes (DM-2) in HIV-infected patients
and the concomitant use of metformin (MTF) and non-nucleoside reverse
transcriptase inhibitors (NRTI) is rising. Through inhibition of NADH
dehydrogenase and DNA pol-gamma, both drugs hinder oxidative phosphorylation that
may lead to lactic acidosis (LA). Among NRTIs, abacavir and tenofovir have the
lowest mitochondrial toxicity, with only a few LA cases reported2-4. We describe
here a case of MTF-associated LA (MALA) secondary to the interaction with NRTI.
PMID- 26426600
TI - TIIA attenuates LPS-induced mouse endometritis by suppressing the NF-kappaB
signaling pathway.
AB - Endometritis is one of the main diseases that harms the dairy cow industry.
Tanshinone IIA (TIIA), a fat-soluble alkaloid isolated from Salviae
miltiorrhizae, has been reported to have potent anti-inflammatory properties.
However, the anti-inflammatory effects of TIIA on a mouse model of
lipopolysaccharide (LPS)-induced endometritis remain to be elucidated. The
purpose of the present study was to investigate the effects of TIIA on LPS
induced mouse endometritis. TIIA was intraperitoneally injected 1 h before and 12
h after perfusion of LPS into the uterus. A histological examination was then
performed, and the concentrations of myeloperoxidase (MPO) and nitric oxide (NO)
in the uterine tissue were determined. The levels of tumor necrosis factor-alpha
(TNF-alpha) and interleukin-1beta (IL-1beta) in a homogenate of the uterus were
detected by enzyme-linked immunosorbent assay. The extent of phosphorylation of
IkappaBalpha and p65 was detected by Western blotting. TIIA markedly reduced the
infiltration of neutrophils, suppressed MPO activity and the concentration of NO,
and attenuated the expression of TNF-alpha and IL-1beta. Furthermore, TIIA
inhibited the phosphorylation of the nuclear factor-kappa B (NF-kappaB) p65
subunit and the degradation of its inhibitor IkappaBalpha. All the results
suggest that TIIA has strong anti-inflammatory effects on LPS-induced mouse
endometritis.
PMID- 26426601
TI - Monitoring guanine photo-oxidation by enantiomerically resolved Ru(II)
dipyridophenazine complexes using inosine-substituted oligonucleotides.
AB - The intercalating [Ru(TAP)2(dppz)](2+) complex can photo-oxidise guanine in DNA,
although in mixed-sequence DNA it can be difficult to understand the precise
mechanism due to uncertainties in where and how the complex is bound. Replacement
of guanine with the less oxidisable inosine (I) base can be used to understand
the mechanism of electron transfer (ET). Here the ET has been compared for both
Lambda- and Delta-enantiomers of [Ru(TAP)2(dppz)](2+) in a set of sequences where
guanines in the readily oxidisable GG step in {TCGGCGCCGA}2 have been replaced
with I. The ET has been monitored using picosecond and nanosecond transient
absorption and picosecond time-resolved IR spectroscopy. In both cases inosine
replacement leads to a diminished yield, but the trends are strikingly different
for Lambda- and Delta-complexes.
PMID- 26426602
TI - Polymorphisms in the interleukin 4, interleukin 4 receptor and interleukin 13
genes and allergic phenotype: A case control study.
AB - PURPOSE: Interleukin 4 (IL4), interleukin 4 receptor (IL4R) and interleukin 13
(IL13) play a key role in the pathogenesis of allergy and asthma development. IL4
and IL13 strongly influence bronchial hyperreactivity in response to allergen,
airway remodeling, airway inflammation and airway smooth muscle proliferation.
Both IL4 and IL13 exert biologic effect via interleukin 4 receptor. The aim of
this study was to evaluate the impact of the polymorphisms within interleukin 4
(rs2243250, rs2227284), interleukin 4 receptor alpha chain (rs1805010, rs1805011)
and interleukin 13 (rs20541) genes on the incidence of allergic phenotype in
Polish pediatric population. MATERIAL/METHODS: We compared 177 asthmatic
pediatric patients with 194 healthy children. Five polymorphisms within IL4, IL13
and IL4Ralpha genes were analyzed. Genotypes of four polymorphisms (rs2243250,
rs2227284, rs1805011, rs20541) were assigned by TaqMan SNP Genotyping Assays
(Applied Biosystems), whereas rs18050100 polymorphism was established using PCR
RFLP method. RESULTS: We observed an association of rs1805011 polymorphism of
IL4Ralpha gene with allergy (p=0.021), mild asthma (p=0.00005) and atopic
dermatitis (p=0.0056). Significant correlation was found between rs20541 in IL-13
gene and the positive skin prick test results (p=0.029), along with rs2243250
polymorphism with clinical atopy (p=0.033) and rs2227284 with total IgE levels
(p=0.00047). No associations were found for rs1805010. CONCLUSIONS: Our results
indicate that rs1805011 polymorphism of IL4Ralpha gene seems to influence allergy
risk, especially mild asthma and atopic dermatitis predisposition in Polish
children. Subgroup analysis of three other SNPs revealed possible influence on
allergy development.
PMID- 26426603
TI - Cost-Effectiveness Analysis on Endoscopic Surveillance Among Western Patients
With Barrett's Esophagus for Esophageal Adenocarcinoma Screening.
AB - Incidence of esophageal adenocarcinoma (EAC) has risen rapidly over the past
decades in Western countries. As a premalignant lesion, Barrett's esophagus (BE)
is an established risk factor of EAC. This study estimated the impact of
surveillance endoscopy for BE on population's survival upon EAC by a whole
population cost-effectiveness analysis among modeled Western population.
Possibilities and survival payoffs were retrieved through literature searching
based on PubMed database. Patients with BE were classified as adequate
surveillance (AS), inadequate surveillance (IAS), and no surveillance groups.
Direct cost of endoscopy per person-year was estimated from diagnosis of BE to
before diagnosis of EAC in the whole-population model, whereas the payoff was 2
year disease-specific survival rate of EAC. AS for patients with BE had lower
cost-effectiveness ratio (CER) than that of IAS group, as well as lower
incremental cost-effectiveness ratio (6116 ?/% vs 118,347 ?/%). Prolonging the
surveillance years could decrease the yearly cost in whole population and also
relevant CERs, despite increased total cost. Increasing the proportion of
participants in AS group could improve the survival benefit. The maximal payoff
was up to 2-year mortality reduction of 2.7 per 100,000 persons by spending extra
? 1,658,913 per 100,000 person-years. A longer endoscopic surveillance among BE
subpopulation plan can reduce yearly budget. Attempt to increase the proportion
of AS participants can induce decline in population mortality of EAC, despite
extra but acceptable expenditure. However, regarding optimal cost-effectiveness,
further studies are still required to identify a high-risk subpopulation out of
BE patients for endoscopic surveillance.
PMID- 26426604
TI - Isolated Total Rupture of Extraocular Muscles.
AB - Total rupture of extraocular muscles is an infrequent clinical finding. Here we
conducted this retrospective study to evaluate their causes of injury, clinical
features, imaging, surgical management, and final outcomes in cases of isolated
extraocular muscle rupture at a tertiary center in China. Thirty-six patients
were identified (24 men and 12 women). Mean age was 34 years (range 2-60). The
right eye was involved in 21 patients and the left 1 in 15. A sharp object or
metal hook was the cause of this lesion in 16 patients, sinus surgery in 14
patients, traffic accident in 3 patients, orbital surgery in 2 patients, and
conjunctive tumor surgery in 1 patient. The most commonly involved muscles were
medial (18 patients) and inferior rectus muscles (13 patients). The function of
the ruptured muscles revealed a scale of -3 to -4 defect of ocular motility and
the amount of deviation in primary position varied from 10 to 140 PD (prism
diopter). Computerized tomography (CT) confirmed the presence of ruptured
muscles. An end-to-end muscle anastomosis was performed and 3 to 5 mm of muscle
was resected in 23 patients. When the posterior border of the injured muscle
could not be identified (13 patients), a partial tendon transposition was
performed, together with recession of the antagonist in most patients, whereas a
recession of the antagonist muscle plus a resection of the involved muscle with
or without nasal periosteal fixation was performed in the remaining patients.
After an average of 16.42 months of follow-up an excellent result was achieved in
23 patients and results of 13 patients were considered as a failure. In most
patients, the posterior border of the ruptured muscle can be identified and an
early surgery can be performed to restore function. Alternatively, a partial
tendon transposition should be performed. When muscular rupture is suspected, an
early orbital CT is required to confirm this possibility, which can then verify
the necessity for an early surgical intervention.
PMID- 26426605
TI - Socioeconomic Disparities in Colorectal Cancer Screening in Korea: A Nationwide
Cross-Sectional Study.
AB - Colorectal cancer (CRC) is a common cancer worldwide. The incidence and mortality
rates of CRC are higher among lower socioeconomic status (SES) populations. We
investigated the association between different indicators of SES and CRC
screening rates in Korea. The eligible study population included males and
females aged 50 to 74 years who participated in a nationwide cross-sectional
survey (2010-2012). The "compliance with recommendation" category was applicable
to participants who had undergone a fecal occult blood test (FOBT), double
contrast barium enema, or colonoscopy within 1, 5, or 10 years, respectively. In
total, 6221 subjects (51.4% female, 55.6% aged 50 years) were included in the
final analysis. Lower household income was significantly negatively related to
compliance with screening recommendations (P for trend < 0.01) and marginally
significantly related to noncompliance with recommendations (P for trend = 0.07).
Older age and poor self-reported health were associated with the screening rate
using the FOBT; male sex, older age, higher household income, having supplemental
insurance, family history of cancer, and poor self-reported health were
associated with a higher screening rate using colonoscopy. Lower household income
was associated with a higher screening rate using the FOBT and with a lower
screening rate using colonoscopy. To increase the rate of CRC screening using
colonoscopy, efforts should be made toward improving the education and promotion
of screening to the low household income target population.
PMID- 26426606
TI - Citrus Fruit Intake Substantially Reduces the Risk of Esophageal Cancer: A Meta
Analysis of Epidemiologic Studies.
AB - Many epidemiologic studies indicate a potential association between fruit and
vegetable intake and various cancers. The purpose of this meta-analysis is to
investigate the association between citrus fruit intake and esophageal cancer
risk. The authors conducted a comprehensive search on PubMed, EMBASE, and the
Cochrane Library from inception until July 2014. Studies presenting information
about citrus intake and esophageal cancer were analyzed. The authors extracted
the categories of citrus intake, study-specific odds ratio or relative risk, and
the P value and associated 95% confidence intervals for the highest versus lowest
dietary intake of citrus fruit level. The association was quantified using meta
analysis of standard errors with a random-effects model. Thirteen case-control
studies and 6 cohort studies were eligible for inclusion. Citrus intake may
significantly reduce risk of esophageal cancer (summary odds ratio = 0.63; 95%
confidence interval = 0.52-0.75; P = 0), without notable publication bias
(intercept = -0.79, P = 0.288) and with significant heterogeneity across studies
(I = 52%). The results from epidemiologic studies suggest an inverse association
between citrus fruit intake and esophageal cancer risk. The significant effect is
consistent between case-control and cohort studies. Larger prospective studies
with rigorous methodology should be considered to validate the association
between citrus fruits and esophageal cancer.
PMID- 26426607
TI - Three-Dimensional Reconstruction Modeling of the Spatial Displacement, Extent and
Rotational Orientation of Undisplaced Femoral Neck Fractures.
AB - The purpose of this study was to employ a new three-dimensional (3D)
reconstruction and modeling method to measure displacement of undisplaced femoral
neck fractures (Garden stages I and II). We also aimed to evaluate the
effectiveness of the Garden classification for determining the displacement of
undisplaced femoral neck fractures. A total of 120 consecutive patients with
undisplaced femoral neck fractures were enrolled between 2012 and 2014, including
60 within the Garden I group and 60 within the Garden II group. The displacements
of the femoral head center (d1) and the lowest point of the fovea capitis femoris
(d2) and rotational displacement of the femoral head (alpha) in the 3D model were
measured with 3D computed tomography reconstruction and modeling. Five observers,
trauma surgeons, were asked to found the centers of the femoral heads and the
deepest points of the foveae. The intraobserver and inter-observer agreements
were calculated using Fleiss' kappa. The inter-observer and intra-observer kappa
values were 0.937 and 0.985, respectively. Current method has good reliability.
We discovered that many participants in our study had been misclassified by an
anterior-posterior radiograph as having an "incomplete" fracture. In incomplete
fracture of Garden stage I group, the average displacements d1 and d2 were 3.69
+/- 1.77 mm and 14.51 +/- 1.91 mm, respectively. The mean alpha was 4.91 degrees
+/- 2.49 degrees . For impacted fracture of Garden stage I, significant spatial
displacement in the impacted fractures was observed (d1: 6.22 +/- 3.36 mm; d2:
10.30 +/- 5.73 mm; and alpha: 17.83 degrees +/- 10.72 degrees ). Similarly,
significant spatial displacement was observed among the Garden stage II group
(d1: 7.16 +/- 4.58 mm; d2: 12.95 +/- 8.25 mm; and alpha: 18.77 degrees +/- 9.10
degrees ). There was no significant difference in alpha, d1, and d2 between
impacted fracture and Garden stage II groups (P > 0.05). However, significant
differences were found between incomplete fracture and Garden stage II groups (P
< 0.05). Our findings suggest that 3D reconstruction and modeling may be a better
tool for assessing femoral neck fractures than the Garden classification.
Undisplaced femoral neck fractures showed variable degrees of displacement and
were not undisplaced, stable fractures. Garden classification for undisplaced
femoral neck fractures has certain limitations.
PMID- 26426608
TI - Radioguided Adrenal Surgery: Access in Complex Situations: Technical Notes.
AB - The laparoscopic adrenalectomy is considered as the procedure of choice for the
treatment of adrenal hyperplasia and tumor lesions. However, some special
situations may limit the use of this method due to the difficulty to locate the
gland and perform the lesion excision. We analyze 2 patients of a left adrenal
tumor, explaining how they have overcome the difficulties in both situations. The
first case was a patient with a history of intra-abdominal surgery and the other
patient suffered from severe obesity. We performed with the use of the gamma
probe, and the 2 cases, was of great help to access and glandular localization.
The help of gamma probe test was achieved in the surgical bed, that removal was
complete. The use of the portable gamma probe facilitated the access to the left
adrenal gland as well as conducting the glandular excision without delay, despite
the difficulties due to the intra abdominal surgery caused by the previous
surgery, and in the case of severe obesity.
PMID- 26426609
TI - Improved Sepsis Alert With a Telephone Call From the Clinical Microbiology
Laboratory: A Clinical Trial.
AB - Early sepsis attention is a standard of care in many institutions and the role of
different specialists is well recognized. However, the impact of a telephone call
from a specialist in Clinical Microbiology upon blood cultures request has not
been assessed to the best of our knowledge. We performed telephone calls followed
by an interview with physicians and nurses in charge of adult patients (> 18
years old) whose blood cultures had just been received in the Microbiology
Laboratory in a tertiary hospital. Patients were randomly classified in 2
different groups: group A (telephone call performed) and group B (no telephone
call). At the end of the telephonic intervention, recommendations on the use of
microbiology and biochemical tests as well as on the management and antibiotic
therapy of sepsis were made if required. We included 300 patients. Of those
fulfilling standard criteria of sepsis, 30.3% of the nurses and 50% of the
physicians immediately recognized it. Advice to optimize the use of biochemical
and microbiological tests was provided in 36% of the cases and to improve
antimicrobial therapy in 57.6%. The median number of days of antibiotic use in
groups A and B were, respectively, 6 days (IQR: 2-12) vs 9 days (IQR: 4-16) P =
0.008 and the median number of prescribed daily doses of antimicrobials (6 [IQR:
3-17] vs 10 [IQR: 5-22] P = 0.016) were lower in group A. We estimate a
reduction, only in the use of antibiotic, of 1.8 million Euros per year. A
telephone call with management advice, immediately after the arrival of blood
cultures in the Microbiology Laboratory improves the recognition of sepsis and
the use of diagnostic resources and reduces antimicrobial consumption and
expenses.
PMID- 26426610
TI - Omission of Chemotherapy in Early Stage Nasopharyngeal Carcinoma Treated with
IMRT: A Paired Cohort Study.
AB - The objective of this study was to evaluate the necessity of concurrent
chemotherapy in T1-2N1 nasopharyngeal carcinoma (NPC) patients treated with
intensity-modulated radiation therapy (IMRT). The retrospective analysis was
conducted using the paired comparison method. We matched cases to controls using
the greedy matching algorithm with 1:1 control to case ratio. Controls were
matched to cases by factors including age, gender, T stage, and duration of RT.
The control group included patients received IMRT alone. In another group,
concurrent chemotherapy (DDP 40 mg2/m/w) was administrated to each paired
patient. From Jan 2009 to Dec 2011, a total of 86 well-balanced T1-2N1 (2002 UICC
staging system) NPC patients were retrospectively analyzed. Half of them (43
patients) received radical IMRT alone and another 43 received concurrent
chemotherapy with IMRT (CCRT). Median follow-up is 37.4 months (4.8-66.2 months).
All patients received a radiation dose of 66 Gy/30Fx. In the CCRT group, all
patients received a cumulative dose of >= 200 mg/m2. The differences of 3-year
overall survival (OS), 3-year progression-free survival (PFS), 3-year relapse
free survival (RFS), and 3-year metastasis-free survival (MFS) between 2 groups
were not significant (P > 0.05). The most frequently increased toxicities related
to chemotherapy were mild to moderate leukopenia (P = 0.003) and mild anemia (P =
0.008).Omission of weekly cisplatin chemotherapy resulted in comparable survival
outcomes to CCRT in IMRT populations. More data from future randomized trials are
warranted to further confirm it.
PMID- 26426611
TI - Strong Neck Accumulation of 131I Is a Predictor of Incomplete Low-Dose
Radioiodine Remnant Ablation Using Recombinant Human Thyroid-Stimulating Hormone.
AB - The purpose of this study was to identify the factors that predict incomplete low
dose radioiodine remnant ablation (RRA) with recombinant human thyroid
stimulating hormone (rhTSH) and to report the adverse events associated with this
treatment. Between 2012 and 2014, 43 consecutive patients with thyroid cancer
received low-dose RRA with rhTSH after total thyroidectomy. We retrospectively
investigated the adverse events during low-dose RRA and during diagnostic whole
body scan (DxWBS) using rhTSH, and analyzed the rate of RRA completion and the
associations between RRA completion and various clinical/pathological factors.
Complete RRA was seen in 33 (76.7%) patients, and incomplete RRA was observed in
10 (23.3%). Patients with incomplete RRA had stronger neck accumulation of 131I
than those with complete RRA (P < 0.001). Adverse events at RRA and DxWBS were
seen in 12 and 9 patients, respectively. All events at RRA were grade 1, with one
exception (grade 2 vertigo after rhTSH administration). The rate of adverse
events at DxWBS was significantly higher in patients with adverse events seen at
RRA (risk ratio, 3.778, P = 0.008). Strong neck accumulation of 131I is
significant independent predictor of incomplete low-dose RRA. The risk of adverse
events at DxWBS was higher in patients who experienced adverse events at RRA than
in those who did not.
PMID- 26426612
TI - Upregulated Expression of A20 on Monocytes is Associated With Increased Severity
of Acute-on-Chronic Hepatitis B Liver Failure: A Case-Control Study.
AB - A20 expression is increased in various inflammatory diseases. However, the role
of A20 in acute-on-chronic liver failure is unknown. This study was to evaluate
A20 expression on monocytes and its associations with the severity of acute-on
chronic hepatitis B liver failure (ACHBLF). Thirty-seven patients with ACHBLF, 20
patients with chronic hepatitis B (CHB), and 15 healthy controls (HC) were
enrolled in this case-control study. A20-positive monocytes were identified using
flow cytometry. Serum levels of interleukin (IL)-10, IL-12p70, and TNF-alpha were
determined using bead cytometry. A20 and IL-10 expressions were examined in THP-1
cells stimulated by lipopolysaccharide (LPS). The frequency of A20+ monocytes was
significantly increased in patients with ACHBLF compared with HC (median
[interquartile range, IQR]: 15.7 [22.8]% vs 2.5 [4.7]%, P < 0.001). Increased
monocyte A20 expression was detected during the progression phase (including the
mild/moderate and severe grades of ACHBLF) compared with patients in the recovery
phase (both P < 0.05), and in the ACHBLF worsening group compared with patients
in the improvement group (P < 0.001). LPS treatment upregulated A20 and IL-10
expressions in THP-1 cells. A20 expression on monocytes from patients with ACHBLF
was positively correlated with total bilirubin (r = 0.60, P = 0.0001), direct
bilirubin (r = 0.63, P < 0.0001), and MELD score (r = 0.43, P = 0.008), and
inversely with prothrombin activity (r = -0.33, P = 0.046). IL-10 and TLR4
expression levels in monocytes, and serum levels of IL-10, IL-12p70, and TNF
alpha were increased in patients with ACHBLF compared with patients with CHB and
HC. Increased A20 expression on monocytes was associated with the severity of
ACHBLF.
PMID- 26426613
TI - Pro-Inflammatory Cytokines in Nasopharyngeal Aspirate From Hospitalized Children
With Respiratory Syncytial Virus Infection With or Without Rhinovirus
Bronchiolitis, and Use of the Cytokines as Predictors of Illness Severity.
AB - Respiratory syncytial virus (RSV) and human rhinovirus (HRV) respiratory
infection in children induce production of inflammatory interleukins (ILs) in the
respiratory epithelium. As IL(s) determine the severity of illness, the purpose
of this study was to identify the pro-inflammatory IL(s) that could be
predictor(s) of clinical severity. One hundred and fifteen patients <2 years old
with bronchiolitis due to RSV and /or HRV and 38 controls were selected from a
hospital and an outpatient clinic. Clinical data of all patients were recorded.
Severity was defined by the number of days with oxygen need. Nasopharyngeal
aspirates (NPA) were collected to perform viral diagnosis by quantitative reverse
transcription and polymerase chain reaction (qRT-PCR) and to quantify ILs: TNF
alpha, IL-10, IL-6, IL-1beta, and IL-8, by flow cytometry. Simple and multiple
regression and receiver operating characteristic (ROC) curves were used for
statistical analysis. Of the patients selected 60 were single RSV, 28 RSV
associated to HRV, and 27 single HRV. All patients (115) showed significantly
higher IL levels when compared with controls. Levels of IL-6, IL-1beta, and IL-8
detected in NPA from RSV single and associated to HRV were significantly higher
than HRV infected and positively associated with days requiring O2.Levels of IL
6, IL-1beta, and IL-8 detected in NPA from patients infected with RSV only or
with both RSV and HRV are increased, and any of those 3 cytokines may have a
predictive value for the number of days with need of supplemental oxygen.
PMID- 26426614
TI - Serum Fetuin-A Associated With Fatty Liver Index, Early Indicator of Nonalcoholic
Fatty Liver Disease: A Strobe-Compliant Article.
AB - Increased fetuin-A has been reported in association with type 2 diabetes and
other metabolic diseases. However, the large population data concerning fetuin-A
and nonalcoholic fatty liver disease (NAFLD) were limited. In this study, we
aimed to investigate the association of serum fetuin-A with fatty liver index
(FLI), the indicator of NAFLD. A population-based cross-sectional analysis was
performed in 5219 middle-aged and elderly participants who were recruited from 2
nearby urban communities in Shanghai, China. Serum fetuin-A concentrations were
measured by enzyme-linked immunosorbent assay (ELISA). The fourth quartiles of
FLI, alanine aminotransferance (ALT), aspartate aminotransferance (AST), and
gamma-glutamyl transpeptadase (GGT) were defined as elevated FLI, ALT, AST, and
GGT, respectively. Fetuin-A was positively associated with log-transformed-FLI,
ALT, -AST, and -GGT after adjustment for the confounding factors (all P < 0.05).
Multivariate logistic regression analysis showed that each one-standard deviation
increase in serum fetuin-A (120.1 mg/L) was associated with 12% (95% confidence
interval [CI] 1.01-1.25, P = 0.04), 13% (95% CI 1.06-1.21, P < 0.001), and 10%
(95% CI 1.03-1.17, P = 0.005) increased risk of elevated FLI, ALT, and AST,
respectively. Categorical analysis showed that as compared to the lowest
quartile, the highest quartile of serum fetuin-A associated with a 35% (95% CI
0.98-1.86), 50% (95% CI 1.24-1.83), and 33% (95% CI 1.10-1.60) increased risk of
elevated FLI, ALT, and AST, respectively. No significant association was found
with GGT. In Chinese adults, serum fetuin-A concentrations were significantly
associated with elevated FLI, ALT, and AST, the early indicators of NAFLD.
PMID- 26426615
TI - Serum Bone Morphogenic Protein-4 Contributes to Discriminating Coronary Artery
Disease Severity.
AB - Bone morphogenic protein 4 (BMP-4) is a known pro-inflammatory and pro
atherogenic cytokine. Here, we investigated whether the serum BMP-4 level
predicts coronary artery disease (CAD) severity in humans. We measured serum BMP
4 concentrations in 1044 consecutive patients who underwent elective coronary
angiography and percutaneous coronary intervention. CAD severity was estimated by
the number of diseased vessels showing >= 50% diameter stenosis. Among males, the
serum BMP-4 level was significantly lower in patients with multivessel disease
(MVD) compared with those with single-vessel disease (SVD) (16.3 +/- 22.6 vs.
22.0 +/- 28.4 pg/mL, P < 0.01). After adjustment for other cardiovascular risk
factors, a high serum BMP-4 level was an independent predictor for a decreased
risk of MVD (odds ratio, 0.992; 95% confidence interval [CI], 0.985-0.998; P =
.01) and patients in the lower tertile were 1.55-fold more likely to have MVD
compared with upper tertile patients. Receiver-operating characteristic curve
analysis demonstrated that the serum BMP-4 level had a 54% sensitivity and 54%
specificity for predicting MVD (area under the curve [AUC], 56.5%; 95% CI, 51.9
61.0%; P < 0.01). Serum BMP-4 improved the predictive capability of risk factors
for MVD (AUC with and without BMP-4: 64.9 and 63.6%, respectively). Considering
the likelihood ratio and number of parameters, adding the serum BMP-4 level
provided a better-fit model for predicting MVD compared with the model consisting
of conventional risk factors (likelihood ratio chi2 = 6.20, P = .01). However,
an association between serum BMP-4 and CAD was not observed in females.Serum BMP
4 levels are independently associated with CAD severity and contribute to
discriminating CAD severity in males.
PMID- 26426616
TI - Ocular Trauma Score in Siderosis Bulbi With Retained Intraocular Foreign Body.
AB - The purpose of this study was to investigate the clinical characteristic and
visual outcome of siderosis bulbi with retained intraocular foreign body (IOFB)
and to validate the predictive value of the Ocular Trauma Score (OTS) in
siderosis bulbi. Certain numerical values rendered to the OTS variables at
present were summated (Table 1) and converted into 5 OTS categories as performed
in the OTS study. The prognostic value of OTS was first assessed in cases of
siderosis bulbi resulting from a chemical reaction of retained IOFBs. Twenty-four
eyes of 24 patients diagnosed with siderosis bulbi who underwent surgery between
2007 and 2013 at our medical centre were reviewed. Due to patients' ignorance in
ocular injuries, delayed presentation by the patient (54.17%) and no history of
trauma (16.67%) were the most common cause of siderosis bulbi with IOFB
retention. The main symptom of all these patients was impaired vision. The most
common complications were cataract (23/24, 95.83%), followed by retinal
pigmentary degeneration (15/22, 68.18%), iris heterochromia (14/24, 58.33%),
pupillary mydriasis (10/21, 47.62%), secondary glaucoma (6/24, 25.00%), relative
afferent pupillary defect (6/24, 25.00%), and retinal detachment (3/24, 12.50%).
IOFBs were removed in 22 eyes (91.67%), except 2 enucleated eyes with absolute
glaucoma (8.33%). Among all the patients (24 eyes), the best-corrected visual
acuity improved in 63.64%, unchanged in 18.18% and deteriorated in 18.18% after
surgical intervention. No statistically significant difference was found between
the categorical distributions of our patients and those in the OTS study group.
Further promotion and education on eye protection are needed to minimize visual
loss from siderosis bulbi. The OTS, which was designed to predict visual outcomes
of general ocular trauma, may also provide reliable information about the
prognosis of siderosis bulbi resulting from a chemical reaction of retained
IOFBs.
PMID- 26426617
TI - Value of Chromosome 9p21 Polymorphism for Prediction of Cardiovascular Mortality
in Han Chinese Without Coronary Lesions: An Observational Study.
AB - Variants at chromosome 9p21 are associated with coronary artery disease (CAD).
However, the longitudinal effects of 9p21 variants on cardiovascular mortality
remain controversial and may depend on whether the patient has CAD. We tested the
hypothesis that the single-nucleotide polymorphism (SNP) rs4977574 is associated
longitudinally with cardiovascular death in patients without detectable coronary
lesions. We enrolled patients who underwent coronary angiography for angina
pectoris but had normal angiographic findings. Laboratory analyses and rs4977574
TaqMan genotyping were performed using fasting blood samples collected during
hospitalization. Cardiovascular and all-cause mortality rates were acquired from
a national database. Among the 679 enrolled subjects with neither myocardial
infarction nor an angiographic coronary lesion, 28 (19.0%) of the 147 homozygous
GG carriers suffered a cardiovascular death, compared with 63 (11.8%) of the 532
subjects with the AG or AA genotype during the median 12.3 years (interquartile
range 8.6-12.7 years) of follow-up. In a recessive model, cardiovascular
mortality was significantly higher in subjects with the GG genotype than in those
with the other genotypes (hazard ratio, 1.69, 95% confidence interval 1.08 to
2.64; P = 0.021). In this follow-up study, rs4977574, a tag SNP at chromosome
9p21, was shown to be associated with cardiovascular mortality in Taiwanese
patients with angina pectoris but no coronary lesions.
PMID- 26426618
TI - Association Between Tooth Loss, Body Mass Index, and All-Cause Mortality Among
Elderly Patients in Taiwan.
AB - To date, the effect of tooth loss on all-cause mortality among elderly patients
with a different weight group has not been assessed. This retrospective cohort
study evaluated the data obtained from a government-sponsored, annual physical
examination program for elderly citizens residing in Taipei City during 2005 to
2007, and follow-up to December 31, 2010. We recruited 55,651 eligible citizens
of Taipei City aged >= 65 years, including 29,572 men and 26,079 women, in our
study. Their mortality data were ascertained based on the national death files.
The number of missing teeth was used as a representative of oral health status.
We used multivariate Cox proportional hazards regression analysis to determine
the association between tooth loss and all-cause mortality. After adjustment for
all confounders, the hazard ratios (HRs) of all-cause mortality in participants
with no teeth, 1 to 9 teeth, and 10 to 19 teeth were 1.36 [95% confidence
interval (CI): 1.15-1.61], 1.24 (95% CI: 1.08-1.42), and 1.19 (95% CI: 1.09
1.31), respectively, compared with participants with 20 or more teeth. A
significant positive correlation of body mass index (BMI) with all-cause
mortality was found in underweight and overweight elderly patients and was
represented as a U-shaped curve. Subgroup analysis revealed a significant
positive correlation in underweight (no teeth: HR = 1.49, 95% CI: 1.21-1.83; 1-9
teeth: HR = 1.23, 95% CI: 1.03-1.47; 10-19 teeth: HR = 1.20, 95% CI: 1.06-1.36)
and overweight participants (no teeth: HR = 1.37, 95% CI: 1.05-1.79; 1-9 teeth:
HR = 1.27, 95% CI: 1.07-1.52). The number of teeth lost is associated with an
increased risk of all-cause mortality, particularly for participants with
underweight and overweight.
PMID- 26426619
TI - Early Immunoglobulin Therapy and Outcomes in Kawasaki Disease: A Nationwide
Cohort Study.
AB - Kawasaki disease is the leading cause of acquired heart disease among children in
most industrialized countries; however, only few descriptive studies have
discussed the pros and cons of early immunoglobulin therapy. This study aimed to
see the effect of early immunoglobulin therapy on Kawasaki disease outcomes.
Patients who received immunoglobulin therapy for the first time were enrolled.
Basic data were analyzed for descriptive epidemiology. If there was no
prescription of antipyretics 4 to 12 days before admission, those patients were
regarded as early immunoglobulin therapy group. The risk for acute aneurysm,
requiring long-term anticoagulant therapy and recurrence rate were compared. Of
5235 patients with first attack of Kawasaki disease, 1156 received early
immunoglobulin therapy. The odds ratios for acute aneurysm and needing long-term
anticoagulant therapy were 0.99 (95% confidence interval [CI], 0.75-1.29) and
1.06 (95% CI, 0.86-1.31), respectively. The recurrence rate was higher for the
early immunoglobulin therapy group, with an adjusted hazard ratio of 1.38 (95%
CI, 1.29-1.47). Early immunoglobulin therapy might not be beneficial for the
coronary outcomes of children with Kawasaki disease in this observational study.
On the contrary, it might be associated with higher recurrence rate. A randomized
controlled study comparing early and late intravenous immunoglobulin therapy
would have probably brought relevant results.
PMID- 26426620
TI - High Agatston Calcium Score of Intracranial Carotid Artery: A Significant Risk
Factor for Cognitive Impairment.
AB - The effect of intracranial internal carotid artery (ICA) calcification on
cognitive impairment is uncertain. Our objective was to investigate whether
intracranial ICA calcification is a significant cognitive predictor for cognitive
impairment. Global cognition and degrees of intracranial ICA calcification of 579
subjects were assessed with Mini-Mental State Examination (MMSE) and Agatston
calcium scoring method, respectively. Other risk factors for cognitive
impairment, including age, education level, hypertension, diabetes mellitus,
smoking, hyperlipidemia, and body mass index, were documented and analyzed for
their associations with cognitive function. In univariate analyses, older age,
lower education level, hypertension, diabetes mellitus, and higher intracranial
ICA Agatston scores were significantly associated with cognitive impairment. In
ordinal logistic regression, only age and total intracranial ICA Agatston score
were significant risk factors for cognitive impairment. After adjustment for the
other documented risk factors, subjects were 7% (95% CI: 5-10; P < 0.001) and 6%
(95% CI: 0-13; P = 0.04) more likely to have lower cognitive category with every
year increment of age and every 100-point increment of the total intracranial ICA
Agatston score respectively. These results suggest an important role of the
intracranial ICA calcification on cognitive impairment.
PMID- 26426621
TI - Relationship of Blood Pressure With Mortality and Cardiovascular Events Among
Hypertensive Patients aged >= 60 years in Rural Areas of China: A Strobe
Compliant Study.
AB - The Eighth Joint National Committee (JNC-8) panel recently recommended a systolic
blood pressure (BP) threshold of >= 150 mmHg for the initiation of drug therapy
and a therapeutic target of <150/90 mmHg in patients >= 60 years of age. However,
results from some post-hoc analysis of randomized controlled trials and
observational studies did not support these recommendations. In the prospective
cohort study, 5006 eligible hypertensive patients aged >= 60 years from rural
areas of China were enrolled for the present analysis. The association between
the average follow-up BP and outcomes (all-cause and cardiovascular death,
incident coronary heart disease [CHD], and stroke), followed by a median of 4.8
years, were evaluated using Cox proportional hazards models adjusting for other
potential confounders. The relationship between BP (systolic or diastolic) showed
an increased or J-shaped curve association with adverse outcomes. Compared with
the reference group of BP <140/90 mmHg, the risk of all-cause death (hazard ratio
[HR]: 2.698; 95% confidence interval [CI]: 1.989-3.659), cardiovascular death
(HR: 2.702; 95% CI: 1.855-3.935), incident CHD (HR: 3.263; 95% CI: 2.063-5.161),
and stroke (HR: 2.334; 95% CI: 1.559-3.945) was still significantly increased in
the group with BP of 140-149/<90 mmHg. Older hypertensive patients with BP of 140
149/<90 mmHg were at higher risk of developing adverse outcomes, implying that
lenient BP control of 140-149/<90 mmHg, based on the JNC-8 guidelines, may not be
appropriate for hypertensive patients aged >= 60 years in rural areas of China.
PMID- 26426622
TI - Prevalence and Predictors of Quality of Recovery at Home After Day Surgery.
AB - Traditionally, major complications and unanticipated admission/readmission rates
were used to assess outcome after day surgery. However, in view of the relative
absence of major complications the quality of recovery (QOR) should be considered
one of the principal endpoints after day surgery. In our study, the level of QOR
is defined by a combination of the Global Surgical Recovery (GSR) Index and the
Quality of Life (QOL). The aim of this study was to analyze prevalence and
predictors of QOR after day surgery on the fourth postoperative day. Elective
patients scheduled for day surgery from November 2008 to April 2010 were enrolled
in a prospective cohort study. Outcome parameters were measured by using
questionnaire packages at 2 time points: 1 week preoperatively and 4 days
postoperatively. Primary outcome parameter is the QOR and is defined as good if
the GSR index >80% as well as the postoperative QOL is unchanged or improved as
compared with baseline. QOR is defined as poor if both the GSR index <= 80% and
if the postoperative QOL is decreased as compared with baseline. QOR is defined
as intermediate in all other cases. Three logistic regression analyses were
performed to determine predictors for poor QOR after day surgery. A total of 1118
patients were included. A good QOR was noted in 17.3% of patients, an
intermediate QOR in 34.8%, and a poor QOR in 47.8% 4 days after day surgery. The
best predictor for poor QOR after day surgery was type of surgery. Other
predictors were younger age, work status, and longer duration of surgery. A
history of previous surgery, expected pain (by the patient) and high long-term
surgical fear were significant predictors of poor QOR in only 1 of 3 prediction
models. The QOR at home 4 days after day surgery was poor in the majority of
patients and showed a significant procedure-specific variation. Patients at risk
for poor QOR can be identified during the preoperative period based on type of
surgery, age, work status, and the duration of the surgery.
PMID- 26426623
TI - Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study
of 41 Patients and Literature Review.
AB - Adult-onset Still's disease (AOSD) is often refractory to standard therapy.
Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy
in single cases and small series of AOSD. We assessed the efficacy of ANK in a
series of AOSD patients. Multicenter retrospective open-label study. ANK was used
due to lack of efficacy to standard synthetic immunosuppressive drugs and in some
cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men)
were recruited. They had a mean age of 34.4 +/- 14 years and a median
[interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At
that time the most common clinical features were joint manifestations 87.8%,
fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical
and laboratory improvement. After 1 year of therapy, the frequency of joint and
cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever
from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to
4.9%. A dramatic improvement of laboratory parameters was also achieved. The
median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK
onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50]
months, the most important side effects were cutaneous manifestations (n = 8),
mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is
associated with rapid and maintained clinical and laboratory improvement, even in
nonresponders to other biologic agents. However, joint manifestations are more
refractory than the systemic manifestations.
PMID- 26426624
TI - Hyperhomocysteinemia as an Early Predictor of Erectile Dysfunction: International
Index of Erectile Function (IIEF) and Penile Doppler Ultrasound Correlation With
Plasma Levels of Homocysteine.
AB - Erectile dysfunction (ED) is inability to achieve and maintain an erection to
permit satisfactory sexual activity. Homocysteine (Hcys) is a sulfur-containing
amino acid synthesized from the essential amino acid methionine. Experimental
models have elucidated the role of hyperhomocysteinemia (HHcys) as a strong and
independent predictor for atherosclerosis progression and impaired cavernosal
perfusion. The aim of this study is to investigate the serum levels of Hcys in
our cohort of patients with ED, to compare these values with these of control
population and to examine Hcys as a predictive marker for those patients who are
beginning to complain mild-moderate ED. A total of 431 patients were enrolled in
the study. The whole cohort was asked to complete the International Index of
Erectile Function (IIEF) questionnaire. The study population was divided in 3
main groups: Group A: 145 patients with no ED serving as a control group; Group
B: 145 patients with mild or mild-moderate ED; Group C: 141 patients with
moderate or severe ED. Each participant underwent blood analysis. All patients
underwent baseline and dynamic penile Doppler ultrasonography. We found in our
cohort mean Hcys plasma concentrations significantly higher than the cut-off
point in both groups B and C (18.6 +/- 4.7 and 28.38 +/- 7.8, respectively). Mean
IIEF score was 27.9 +/- 1.39, 19.5 +/- 2.6, and 11.1 +/- 2.5 for groups A, B, and
C, respectively (P < 0.0001). In the penile Doppler ultrasonography studies, a
high significant inverse correlation was detected between the mean values of the
10th minute's peak-systolic velocity (PSV) and Hcys levels for the groups B and
C. This establishes a dose-dependent association between Hcys and ED.
Furthermore, we showed that Hcys was an earlier predictor of ED than Doppler
studies, as the Hcys increase was present in patients with mild ED even before
abnormal Doppler values.
PMID- 26426625
TI - Modalities of Invasive Arterial Pressure Monitoring in Critically Ill Patients: A
Prospective Observational Study.
AB - Few studies assessed modalities of invasive arterial pressure monitoring (IAPM).
We evaluated effects on measured values of various combinations of transducer
level, catheter access site, and patient position. Prospective observational
study in consecutive adults admitted to a French intensive care unit in 2009 to
2011 and fulfilling our inclusion criteria. Four combinations (B-E) of transducer
level, catheter access site, and patient position were compared with a reference
combination (A) (A: patient supine with all catheters in the same plane and a
single transducer level (M) for zero point reference (Z) aligned on the
phlebostatic axis; B: 45 degrees head-of-bed elevation with M and Z aligned on
the phlebostatic axis; C: 45 degrees head-of-bed elevation with M aligned on the
catheter access site and Z on the phlebostatic axis; D: 45 degrees head-of-bed
elevation with M and Z aligned on the catheter access site; and E: 45 degrees
head-of-bed elevation with M aligned on the phlebostatic axis and Z on the
catheter access site). We included 103 patients, 68 men and 35 women, with a
median age of 69 years (interquartile range [IQR], 56-78); at inclusion, 91
(88.3%) received mechanical ventilation, 45 (43.7%) catecholamines, and 66
(64.1%) sedation. The IAPM access site was femoral in 49 (47.6%) and radial in 54
(52.4%) patients, with 62 of 103 (60.2%) catheters on the right side. Measured
absolute mean arterial pressure values were significantly higher with 3 study
combinations (C-E) than with the reference combination (A). After adjustment, the
differences versus A (median, 83 [IQR, 74-92] mm Hg) remained significant for D
(median, 91 [IQR, 85-100] mm Hg, P < 0.001) and E (median, 88 [IQR, 77-99] mm Hg,
P < 0.001). The difference versus A was not significant for B (median, 85 [IQR,
76-94] mm Hg, P = 0.21) or C (median, 90 [IQR, 84-100] mm Hg, P = 0.006). Several
modalities used for zeroing and/or transducer leveling during IAPM may result in
statistically and clinically significant overestimation of measured mean arterial
pressure values. For patients in the 45 degrees head-of-bed elevation position,
aligning the Z on the phlebostatic axis provides values that are not
significantly different from those obtained using the reference supine modality.
PMID- 26426626
TI - Very Early Lactate Threshold in Healthy Young Men as Related to Oxygen Uptake
Kinetics.
AB - We assessed the correspondence between the V-slope ventilatory threshold (VT) and
the lactate threshold (LT) by using a distinctive slow submaximal ramp protocol
to ensure that sufficient data points exist around the threshold. Twenty healthy
young men participated. A submaximal test based on a prior maximal test (25
watt/min, medium ramp) was performed with an individual slow-ramp protocol (6-17
watt/min, slow ramp), in which the time to reach the VT workload was estimated to
be 10 minutes. The LT was determined visually by detecting a rise above the
resting value, without or with log-log transformation (LT1, LT2). The point at
which the blood lactate exceeded the minimal difference (LMD) of 2 resting values
was also calculated. The VT appeared significantly earlier under the slow-ramp
protocol compared to the medium-ramp protocol (from 19.3 +/- 3.9 to 15.0 +/- 4.0
mL/kg/min VO2, P < 0.001). The mean LT1 and LT2 values appeared even earlier than
the VT (LT1, P = 0.004; LT2, P = 0.002) (LT1, 11.9; LT2, 13.4; LMD, 17.0; VT,
15.0 mL/kg/min VO2). As the mean % of peak VO2, each occurred at 29.9%, 33.7%,
42.5%, and 37.8%. The VT correlated significantly with LT1, LT2, and LMD (r =
0.61, 0.64, 0.80; P = 0.004, 0.002, <0.001). Mean blood lactate showed a similar
trend (1.30, 1.43, 1.81, 1.68 mmol/L, respectively). Furthermore, the
DeltaVO2/Delta work rate slope increased (from 10.8 +/- 0.9 to 11.5 +/- 0.9; P =
0.01) with the slow ramp, and the lower LT was associated with the greater
increase in slope (LT1, r = -0.47, P = 0.03; LT2, r = -0.59, P = .005), that is,
the lower LT was an indication that on the faster medium ramp the slope would
decrease. The LMD and VT did not show this relation. Under slow-ramp exercise
testing in healthy young men, the VT appeared earlier than under medium-ramp
exercise testing. In addition, the LT appeared even earlier (at approximately 30%
of peak VO2) than the VT, although they correlated. This very early onset of LT
was, however, associated with evidence of reduced oxygen uptake kinetics.
PMID- 26426627
TI - Effects of ACEIs Versus ARBs on Proteinuria or Albuminuria in Primary
Hypertension: A Meta-Analysis of Randomized Trials.
AB - Although angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin
receptor blockers (ARBs) belong to a family of therapies that block the renin
angiotensin system and are suggested to improve proteinuria/albuminuria, it is
unclear which is more effective. To compare the effects of ACEIs and ARBs on
proteinuria in primary hypertension by performing a meta-analysis covering
randomized controlled trials (RCTs). We systematically searched MEDLINE, EMBASE,
and the Cochrane Central Register of Controlled Trials from January 1990 to
November 2014. Eligible studies were RCTs of ACEI therapy versus ARB therapy that
reported the albumin excretion rate (AER), albumin (Alb), and urinary albumin
excretion (UAE) as outcomes. Seventeen RCTs, including 17,951 patients (without
limit of race, age, or sex) with a mean duration of 62.6 weeks, were included.
Pooled analysis suggested that ACEIs and ARBs showed no significant differences
in AER/Alb/UAE/24-h urine protein/24-h urine total protein in a comparison of 10
trials (SMD 0.09; 95% CI -0.18-0.36; P = 0.52). No significant differences were
observed in urinary protein/creatinine ratio (UPCR)/urinary albumin/creatinine
ratio (UACR), or albumin/creatinine ratio (ACR) in 7 trials (SMD 0.15; 95% CI
1.88-2.19; P = 0.88). The total outcome of ACEIs and ARBs also showed no
significant difference (SMD 0.13; 95% CI -1.03-1.29; P = 0.83). The efficacies of
ACEIs and ARBs in controlling blood pressure as a secondary indicator were also
similar (SMD -0.50; 95% CI -1.58-0.58; P = 0.37). Based on a meta-analysis of 17
randomized controlled trials including 17,951 patients, we found that ACEIs and
ARBs can reduce urine protein levels, improve blood pressure, and were similarly
effective in terms of reducing urinary protein excretion.
PMID- 26426628
TI - Clinical Analysis of Pulmonary Nocardiosis in Patients With Autoimmune Disease.
AB - Nocardiosis is an opportunistic infection that most commonly involves the lung;
however, only a few case reports of autoimmune disease complicated by pulmonary
nocardiosis exist in the literature. We conducted a retrospective analysis of 24
cases of both autoimmune disease and pulmonary nocardiosis at the Peking Union
Medical College Hospital between 1990 and 2012. Fifty-two cases were hospitalized
with nocardiosis, 24 of whom had at least 1 autoimmune disease before the
diagnosis of pulmonary nocardiosis. The cohort patients consisted of 5 men and 19
women, with a mean age of 44.2 years. All were negative for human
immunodeficiency virus. All but 1 patient had received immunosuppressants,
including corticosteroids, cyclophosphamide, azathioprine, methotrexate, or
hydroxychloroquine. Fever (87.5%), cough (83.3%), and sputum (79.2%) were the
most common clinical manifestations. Ten cases were accompanied by subcutaneous
nodules and/or cutaneous abscesses, and 4 had brain abscess. Half of them were
lymphocytopenic. Thirteen of the 16 cases who underwent lymphocyte subtype
analysis had decreased CD4+ T-cell counts. Nineteen cases had decreased serum
albumin levels. Nocardia was isolated from sputum (13/24), bronchoalveolar lavage
fluid (4/6), lung tissue (5/6), pleural effusions (3/5), skin or cutaneous pus
(7/10), and brain tissue (1/1). The most common imaging findings were air-space
opacities (83.3%), followed by nodules (62.5%), cavitations (45.8%), and masses
(37.5%). Five were administered co-trimoxazole only, and the others were treated
with 2 or more antibiotics. All 5 cases with skin abscesses and 2 of the 4 cases
with brain abscesses were treated by surgical incision and drainage. None
underwent thoracic surgery. Corticosteroid dosages were decreased in all cases,
and cytotoxic agents were discontinued in some cases. Twenty-two cases recovered,
and 2 died. Pulmonary nocardiosis associated with an underlying autoimmune
disease showed a female predominance and presentation at younger age.
Immunosuppressant therapy, lymphocytopenia, particularly low CD4+ T-lymphocyte
counts, and low serum albumin levels may be disease susceptibility factors. Air
space opacities and nodules were the most common chest imaging features, and
disseminated nocardiosis with lung and skin involvement was more common among
them. Early diagnosis and anti-nocardial antibiotics with modulation of the basic
immunosuppressive therapy were important for them.
PMID- 26426630
TI - A Retrospective Cohort Study Comparing Stroke Recurrence Rate in Ischemic Stroke
Patients With and Without Acupuncture Treatment.
AB - Little was known about the effects of acupuncture on stroke recurrence. The aim
of this study is to investigate whether ischemic stroke patients receiving
acupuncture treatment have a decreased risk of stroke recurrence. A retrospective
cohort study of 30,058 newly diagnosed cases of ischemic stroke in 2000 to 2004
was conducted based on the claims of Taiwan National Health Insurance Research
Database. The use of acupuncture treatment and stroke recurrence were identified
during the follow-up period from 2000 to 2009. This study compared the risk of
stroke recurrence between ischemic stroke cohorts with and without acupuncture
treatment by calculating adjusted hazard ratios (HRs) and 95% confidence
intervals (CIs) of acupuncture associated with stroke recurrence in the Cox
proportional hazard model. The stroke recurrence rate per 1000 person-years
decreased from 71.4 without to 69.9 with acupuncture treatment (P < 0.001).
Acupuncture treatment was associated with reduced risk of stroke recurrence (HR
0.88; 95% CI 0.84-0.91). The acupuncture effect was noted in patients with or
without medical treatment for stroke prevention but its impact decreased with
aging of stroke patients. Compared with stroke patients without acupuncture
treatment and medication therapy, the hazard ratios of stroke recurrence for
those had medication therapy only, acupuncture only, and both were 0.42 (95% CI
0.38-0.46), 0.50 (95% CI 0.43-0.57), and 0.39 (95% CI 0.35-0.43), respectively.
This study raises the possibility that acupuncture might be effective in lowering
stroke recurrence rate even in those on medications for stroke prevention.
Results suggest the need of prospective sham-controlled and randomized trials to
establish the efficacy of acupuncture in preventing stroke.
PMID- 26426631
TI - A Cross-Cultural Study on Behaviors When Death Is Approaching in East Asian
Countries: What Are the Physician-Perceived Common Beliefs and Practices?
AB - The primary aim of this study was to explore common beliefs and practices when
death is approaching in East-Asian countries. A cross-sectional survey was
performed involving palliative care physicians in Japan, Korea, and Taiwan.
Measurement outcomes were physician-perceived frequencies of the following when
patient death was approaching: (1) reluctance to take part in end-of-life
discussions, (2) role of family members, (3) home death, and (4) circumstances
surrounding death. A total of 505, 211, and 207 responses were obtained from
Japanese, Korea, and Taiwan physicians, respectively. While 50% of the Japanese
physicians reported that they often or very often experienced families as being
reluctant to discuss end-of-life issues, the corresponding figures were 59% in
Korea and 70% in Taiwan. Two specific reasons to avoid end-of-life discussion,
"bad things happen after you say them out loud" and "a bad life is better than a
good death" were significantly more frequently observed in Taiwan. Prioritizing
the oldest of the family in breaking bad news and having all family members
present at the time of death were significantly more frequently observed in Korea
and Taiwan. Half of Taiwanese physicians reported they often or very often
experienced the patients/family wanted to go back home to die because the soul
would not be able to return from the hospital. In all countries, more than 70% of
the physicians reported certain family members were expected to care for the
patient at home. At the time of death, while no Japanese physicians stated that
they often experienced patients wanted a religious person to visit, the
corresponding figure in Korean and Taiwan was about 40%. Uncovered expression of
emotion was significantly frequently observed in Korean and Taiwan, and 42% of
the Japanese physicians reported family members cleaned the dead body of the
patient themselves. There seem to be significant intercountry differences in
beliefs and practices when death is approaching in East Asian countries. Future
studies on direct observations of patients and families are needed.
PMID- 26426632
TI - Perioperative Allogenenic Blood Transfusion is Associated With Worse Clinical
Outcome for Patients Undergoing Gastric Carcinoma Surgery: A Meta-Analysis.
AB - Whether perioperative allogenic blood transfusion (ABT) has adverse effect on
patients with gastric carcinoma (GC) surgery or not, that is controversial. Our
study evaluated the association between ABT and some clinical outcomes of GC
surgery patients. Data of relevant studies were based on PubMed, EMBASE, and the
Cochrane Library search. The relative risk (RR) of 5-year survival rates, tumor
recurrence, and postoperative complications were performed; subgroup analyses
included district, transfusion rates, age, participants, sex, and tumor stage.
The study was approved by the ethics committee of the First People's Hospital of
Shunde. In total, 9189 participants from 16 studies were included in the meta
analysis. The 5-year survival rate was decreased for the GC patients with ABT (RR
= 0.74, 95% confidence interval [CI] = 0.69-0.79), the risk of tumor recurrence
was significantly higher for ABT patients (RR = 1.82, 95% CI = 1.32-2.51), and
postoperative complications increased in ABT patients (RR = 1.36, 95% CI = 1.02
1.81), respectively; in subgroup analyses, 5-year survival rates were not
associated with the transfusion rates (chi2 = 0.37, P = 0.54). Transfusion for
patients undergoing GC surgery, even low transfusion rates, would reduce the 5
year survival rates, and elevated the risk of tumor recurrence and postoperative
complication.
PMID- 26426633
TI - Does Helicobacter pylori Eradication Reduce the Risk of Open Angle Glaucoma in
Patients With Peptic Ulcer Disease?
AB - To investigate whether Helicobacter pylori (H pylori) eradication would influence
the risk of primary open angle glaucoma (POAG) in patients with peptic ulcer
disease. From the Longitudinal Health Insurance Database 2000, 6061 patients with
peptic ulcer and receiving H pylori eradication therapy were recruited. The study
cohort was subdivided into early (within 1 year) and late (after 1 year)
eradication cohorts. The 24,244 control cohort subjects were those who without
peptic ulcer and without receiving H pylori eradication therapy and were
frequency-matched with the H pylori eradication cohort by age, sex, and the year
of receiving H pylori eradication therapy. The higher incidence of POAG was
observed in late H pylori eradication cohort and in early H pylori eradication
cohort than in control cohort (1.57, 1.32, and 0.95, per 1000 person-year,
respectively). However, overall risk of glaucoma was not significantly higher in
the late eradication than in the early eradication (adjusted hazard ratio = 0.85,
95% confidence interval = 0.48-1.53). The POAG incidence was greater in the late
H pylori eradication cohort when follow-up duration <= 5 years (1.59, per 1000
person-years). However, when follow-up duration >5 years, the incidence of POAG
was greater in the early H pylori eradication cohort (1.68, per 1000 person
years). These relationships were not associated with a significantly increased or
decreased risk of POAG in multivariable analyses. Either early or late H pylori
eradication does not significantly reduce the risk of glaucoma in patients with
peptic ulcer disease compared with normal control.
PMID- 26426634
TI - Low Expression of LDHB Correlates With Unfavorable Survival in Hepatocellular
Carcinoma: Strobe-Compliant Article.
AB - Lactate dehydrogenase B (LDHB) is widely expressed in adult somatic tissue and
plays important roles in the development of human cancers. However, the
association between LDHB expression and the clinicopathological characteristics
of hepatocellular carcinoma (HCC) is not well understood. The study was to detect
the expression of LDHB in human HCC and investigate the association between its
expression and the clinicopathological characteristics of HCC.
Immunohistochemistry (IHC) analysis was performed to characterize the expression
of LDHB in HCC and matched noncancerous tissues. Kaplan-Meier survival and Cox
regression analyses were employed to evaluate the prognosis of 75 HCC patients.
The results showed that the expression of LDHB in HCC was significantly lower
than that in noncancerous tissues. Moreover, the expression level of the LDHB
protein in HCC was correlated with pathological grade (P = 0.037), vascular
invasion (P = 0.037), lymph node metastasis (P = 0.016), and tumor-node
metastasis (TNM) stage (P = 0.007). Cox regression analysis further revealed that
LDHB expression is an independent prognostic factor for disease-free survival (P
= 0.045) and overall survival (P = 0.019).These data are the first to indicate
that LDHB expression is a valuable prognostic biomarker for HCC and that low LDHB
expression suggests unfavorable survival outcomes in HCC patients.
PMID- 26426635
TI - Prognostic Value of the Preoperative Neutrophil to Lymphocyte Ratio in Resectable
Gastric Cancer.
AB - This study aimed to investigate the prognostic value of the preoperative
neutrophil to lymphocyte ratio (NLR) in resectable gastric cancer (GC). This was
a retrospective review of 1030 patients with resectable GC managed between 2005
and 2011. Patients were stratified into 2 groups, those with a preoperative NLR
>3.44 and those with a preoperative NLR <= 3.44. Clinicopathological data
affecting patient prognosis were collected prospectively and analyzed. The high
NLR (> 3.44) group had a higher proportion of a platelet to lymphocyte ratio >
132, tumor size > 4.8 cm, T4 lesions, metastatic tumors, a ratio of metastatic to
examined lymph nodes >0.18, positive resection margins, and presence of vascular
or lymphatic invasion than the low NLR (<= 3.44) group. Patients with a high
preoperative NLR had significantly lower 3- and 5-year overall survival rates
than those with a low preoperative NLR (55.1% vs 71.0% and 47.2% vs 64.1%,
respectively; P < 0.001). Preoperative NLR was a prognostic factor for resectable
GC in multivariate analysis. More aggressive tumor behavior was observed in
patients with resectable GC with a high preoperative NLR than in those with a low
preoperative NLR. High preoperative NLR was an independent unfavorable prognostic
factor. Measurement of this ratio may serve as a clinically accessible and useful
biomarker for patient outcomes.
PMID- 26426629
TI - Characteristics and Outcome of Streptococcus pneumoniae Endocarditis in the XXI
Century: A Systematic Review of 111 Cases (2000-2013).
AB - Streptococcus pneumoniae is an infrequent cause of severe infectious endocarditis
(IE). The aim of our study was to describe the epidemiology, clinical and
microbiological characteristics, and outcome of a series of cases of S.
pneumoniae IE diagnosed in Spain and in a series of cases published since 2000 in
the medical literature. We prospectively collected all cases of IE diagnosed in a
multicenter cohort of patients from 27 Spanish hospitals (n = 2539). We also
performed a systematic review of the literature since 2000 and retrieved all
cases with complete clinical data using a pre-established protocol. Predictors of
mortality were identified using a logistic regression model. We collected 111
cases of pneumococcal IE: 24 patients from the Spanish cohort and 87 cases from
the literature review. Median age was 51 years, and 23 patients (20.7%) were
under 15 years. Men accounted for 64% of patients, and infection was community
acquired in 96.4% of cases. The most important underlying conditions were liver
disease (27.9%) and immunosuppression (10.8%). A predisposing heart condition was
present in only 18 patients (16.2%). Pneumococcal IE affected a native valve in
93.7% of patients. Left-sided endocarditis predominated (aortic valve 53.2% and
mitral valve 40.5%). The microbiological diagnosis was obtained from blood
cultures in 84.7% of cases. In the Spanish cohort, nonsusceptibility to
penicillin was detected in 4.2%. The most common clinical manifestations included
fever (71.2%), a new heart murmur (55%), pneumonia (45.9%), meningitis (40.5%),
and Austrian syndrome (26.1%). Cardiac surgery was performed in 47.7% of
patients. The in-hospital mortality rate was 20.7%. The multivariate analysis
revealed the independent risk factors for mortality to be meningitis (OR, 4.3;
95% CI, 1.4-12.9; P < 0.01). Valve surgery was protective (OR, 0.1; 95% CI, 0.04
0.4; P < 0.01). Streptococcus pneumoniae IE is a community-acquired disease that
mainly affects native aortic valves. Half of the cases in the present study had
concomitant pneumonia, and a considerable number developed meningitis. Mortality
was high, mainly in patients with central nervous system (CNS) involvement.
Surgery was protective.
PMID- 26426636
TI - Acoustic Radiation Force Impulse Measurement in Renal Transplantation: A
Prospective, Longitudinal Study With Protocol Biopsies.
AB - Interstitial fibrosis and tubular atrophy (IF/TA) is a common cause of kidney
allograft loss. Several noninvasive techniques developed to assess tissue
fibrosis are widely used to examine the liver. However, relatively few studies
have investigated the use of elastographic methods to assess transplanted
kidneys. The aim of this study was to explore the clinical implications of the
acoustic radiation force impulse (ARFI) technique in renal transplant patients. A
total of 91 patients who underwent living donor renal transplantation between
September 2010 and January 2013 were included in this prospective study. Shear
wave velocity (SWV) was measured by ARFI at baseline and predetermined time
points (1 week and 6 and 12 months after transplantation). Protocol biopsies were
performed at 12 months. Instead of reflecting IF/TA, SWVs were found to be
related to time elapsed after transplantation. Mean SWV increased continuously
during the first postoperative year (P < 0.001). In addition, mixed model
analysis showed no correlation existed between SWV and serum creatinine (r =
0.2426, P = 0.0771). There was also no evidence of a relationship between IF/TA
and serum creatinine (odds ratio [OR] = 1.220, P = 0.7648). Furthermore, SWV
temporal patterns were dependent on the kidney weight to body weight ratio
(KW/BW). In patients with a KW/BW < 3.5 g/kg, mean SWV continuously increased for
12 months, whereas it decreased after 6 months in those with a KW/BW >= 3.5
g/kg.No significant correlation was observed between SWV and IF/TA or renal
dysfunction. However, SWV was found to be related to the time after
transplantation. Renal hemodynamics influenced by KW/BW might impact SWV values.
PMID- 26426638
TI - CT-Guided Percutaneous Step-by-Step Radiofrequency Ablation for the Treatment of
Carcinoma in the Caudate Lobe.
AB - The location of the caudate lobe and its complex anatomy make caudate lobectomy
and radiofrequency ablation (RFA) under ultrasound guidance technically
challenging. The objective of the exploratory study was to introduce a novel
modality of treatment of lesions in caudate lobe and discuss all details with our
experiences to make this novel treatment modality repeatable and educational. The
study enrolled 39 patients with liver caudate lobe tumor first diagnosed by
computerized tomography (CT) or magnetic resonance imaging (MRI). After
consultation of multi-disciplinary team, 7 patients with hepatic caudate lobe
lesions were enrolled and accepted CT-guided percutaneous step-by-step RFA
treatment. A total of 8 caudate lobe lesions of the 7 patients were treated by
RFA in 6 cases and RFA combined with percutaneous ethanol injection (PEI) in 1
case. Median tumor diameter was 29 mm (range, 18-69 mm). A right approach was
selected for 6 patients and a dorsal approach for 1 patient. Median operative
time was 64 min (range, 59-102 min). Median blood loss was 10 mL (range, 8-16 mL)
and mainly due to puncture injury. Median hospitalization time was 4 days (range,
2-5 days). All lesions were completely ablated (8/8; 100%) and no recurrence at
the site of previous RFA was observed during median 8 months follow-up (range 3
11 months). No major or life-threatening complications or deaths occurred. In
conclusion, percutaneous step-by-step RFA under CT guidance is a novel and
effective minimally invasive therapy for hepatic caudate lobe lesions with well
repeatability.
PMID- 26426639
TI - Comparative Study of Modified Posterior Operation to Treat Kummell's Disease.
AB - The present study aimed at examining the curative effect of modified posterior
operation on treatment of Kummell's disease. About 30 patients of Kummell's
disease with complete image and clinical data treated during June 2004 to July
2013 were conducted with anterior and posterior approaches, respectively.
Kyphotic Cobb angle, fractured vertebra wedge angle, and the anterior and
posterior heights of fractured vertebra were all measured through x-ray before
and after operation, and the pain visual analog scale (VAS) was determined for
evaluating the effect of operations. The injury and restoration of neurological
function were assessed using Frankel classification. Patients in group A were
treated with anterior operation, whereas group B was posterior operation.
Postoperatively, VAS score, kyphotic Cobb angle, anterior vertebra height, and
pathologic vertebra wedge angle were all significantly improved in patients with
Kummell's disease receiving modified posterior operation (group B). Similar
results were also observed in patients with anterior operation. The improvement
of VAS and correction rate of kyphotic Cobb angle indicated equivalent effects of
posterior and anterior operations. Meanwhile, alleviated neurological function
damage was observed in 2 groups. Relevant factor analysis illustrated that there
was no significant correlation of the severity and improvement rate of pain
symptoms with age, medical history, anterior and posterior vertebra heights,
kyphotic Cobb angle, and pathological vertebra wedge angle. Compared with
traditional anterior approach, modified posterior operation, adopting
transpedicular vertebral body grafting combined with vertebral pedicle screw
fixation, could produce equivalent effects on kyphosis correction, pain relief,
and improvement of neurological function in patients with Kummell's disease.
PMID- 26426637
TI - Predictive Value of Ercc1 and Xpd Polymorphisms for Clinical Outcomes of Patients
Receiving Neoadjuvant Therapy: A Prisma-Compliant Meta-Analysis.
AB - Excision repair cross complementing 1 (ERCC1) and xeroderma pigmentosum group D
(XPD) play important roles in the nucleotide excision repair (NER) pathway. The
correlation between ERCC1 polymorphisms (rs11615 and rs3212986) and XPD
polymorphisms (rs13181 and rs1799793) with the response rate and overall survival
of cancer patients who accept neoadjuvant therapy has been extensively
investigated. However, the results are inconclusive. In this study, we performed
a meta-analysis to determine the strength of this correlation. A comprehensive
literature search was conducted in Medline, PubMed, and Embase up to February
2015. A review of all titles and abstracts was performed by 2 of the authors to
screen the articles based on the eligibility criteria. Clinical trials,
observational studies, and epidemiological studies describing ERCC polymorphisms
and neoadjuvant treatment were considered for review. The response rate was
analyzed using pooled odds ratios (ORs) with corresponding 95% confidence
intervals (CIs). Overall survival was assessed using the hazard ratio (HR) with
corresponding 95% confidence intervals. In the present meta-analysis, we
demonstrated that the ERCC1 rs3212986 polymorphism was significantly correlated
with the response rate of esophageal cancer patients to neoadjuvant therapy (OR =
.49, 95% CI = 0.31-0.76, heterogeneity P = 0.480). Furthermore, a considerable
correlation was observed between ERCC1 rs11615 and the response rate of
esophageal cancer patients to neoadjuvant therapy (OR = 0.228, 95% CI = 0.125
0.418, heterogeneity P = 0.291). No correlation was observed in the meta-analysis
of overall survival. The individual studies included in our study differed in
their patient selection and therapeutic protocols, which might lead to some bias
in the results. These findings indicate that the ERCC1 rs11615 and ERCC1 rs312986
polymorphisms may be candidate pharmacogenomic factors capable of predicting the
response rate of esophageal cancer patients who accept neoadjuvant therapy.
Further studies are warranted.
PMID- 26426640
TI - The Relationship Between Educational Years and Phonemic Verbal Fluency (PVF) and
Semantic Verbal Fluency (SVF) Tasks in Spanish Patients Diagnosed With
Schizophrenia, Bipolar Disorder, and Psychotic Bipolar Disorder.
AB - Semantic and verbal fluency tasks are widely used as a measure of frontal
capacities. It has been well described in literature that patients affected by
schizophrenic and bipolar disorders present a worse execution in these tasks.
Some authors have also noted the importance of educational years. Our objective
is to analyze whether the effect of cognitive malfunction caused by apathology is
superior to the expected effect of years of education in phonemic verbal fluency
(PVF) and semantic verbal fluency (SVF) task execution. A total of 62 individuals
took part in this study, out of which 23 were patients with schizophrenic
paranoid disorder, 11 suffered from bipolar disorder with psychotic
symptomatology, 13 suffered from bipolar disorder without psychotic
symptomatology, and 15 participants were nonpathological individuals. All
participants were evaluated with the PVF and SVF tests (animals and tools). The
performance/execution results were analyzed with a mixed-model ANCOVA, with
educational years as a covariable. The effect of education seems to be more
determined by PVF FAS tests than by SVF. With PVF FAS tasks, the expected effect
of pathology disappears when the covariable EDUCATION is introduced. With SVF
tasks, the effect continues to be significant, even though the EDUACTION
covariable dims such effect. These results suggest that SVF tests (animals
category) are better evaluation tools as they are less dependent on the patients'
education than PVF FAS tests.
PMID- 26426641
TI - A Method to Prepare a Descemet's Stripping Automated Endothelial Keratoplasty
(DSAEK) Graft Using Donor Corneas With Narrow Scleral Rims: A Case Report.
AB - Donor corneas with narrow scleral rims are often disqualified for Descemet's
Stripping Automated Endothelial Keratoplasty (DSAEK), mainly because of fluid
leak and low pressure when they are mounted onto an artificial anterior chamber
(AAC). This report describes a novel method to tight-lock a donor cornea with a
narrow scleral rim so that microkeratome cutting is possible, allowing a DSAEK
procedure to be completed. A 50-year-old male suffering from Epstein-Barr virus
(EBV) endotheliitis with resulting corneal edema in his left eye was the subject
of this study. His best corrected visual acuity (BCVA) was 20/600. The patient
underwent a DSAEK procedure; however, the microkeratome cutting of the donor
cornea initially failed due to its narrow scleral rim, which caused the balance
salt solution (BSS) to leak out of the AAC. A doughnut-shaped cushion was made
from a surgical glove, which enabled a tight lock of the cornea to the AAC,
enabling the chamber pressure to be raised and the microkeratome cutting to be
completed. A subsequent DSAEK procedure was performed uneventfully.
Postoperatively, the patient received oral valganciclovir 450 mg b.i.d. to
prevent EBV recurrence. The graft remained clear at 5 months post-op, and the
patient's BCVA improved to 6/7.5. His endothelial count was 1830, which was ~ 79%
of the original value. Inserting a self-made cushion can enable donor corneas
with narrow scleral rims to be used in DSAEK procedures and avoids unwanted
switching from endothelial keratoplasty to penetrating keratoplasty (PKP).
PMID- 26426642
TI - Fructose Malabsorption in Systemic Sclerosis.
AB - The deleterious effect of fructose, which is increasingly incorporated in many
beverages, dairy products, and processed foods, has been described; fructose
malabsorption has thus been reported in up to 2.4% of healthy subjects, leading
to digestive clinical symptoms (eg, pain, distension, diarrhea). Because
digestive involvement is frequent in patients with systemic sclerosis (SSc), we
hypothesized that fructose malabsorption could be responsible for intestinal
manifestations in these patients. The aims of this prospective study were to:
determine the prevalence of fructose malabsorption, in SSc; predict which SSc
patients are at risk of developing fructose malabsorption; and assess the outcome
of digestive symptoms in SSc patients after initiation of standardized low
fructose diet. Eighty consecutive patients with SSc underwent fructose breath
test. All SSc patients also completed a questionnaire on digestive symptoms, and
a global symptom score (GSS) was calculated. The prevalence of fructose
malabsorption was as high as 40% in SSc patients. We also observed a marked
correlation between the presence of fructose malabsorption and: higher values of
GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric
emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption,
the median value of GSS score of digestive symptoms was lower after initiation of
standardized low-fructose diet (4 before vs. 1 after; P = 0.0009). Our study
underscores that fructose malabsorption often occurs in SSc patients. Our
findings are thus relevant for clinical practice, highlighting that fructose
breath test is a helpful, noninvasive method by: demonstrating fructose
intolerance in patients with SSc; and identifying the group of SSc patients with
fructose intolerance who may benefit from low-fructose diet. Interestingly,
because the present series also shows that low-fructose diet resulted in a marked
decrease of gastrointestinal clinical manifestations in SSc patients with
fructose malabsorption, our findings underscore that fructose malabsorption may
play a significant role in the onset of gastrointestinal symptoms in these
patients. Finally, we suggest that fructose malabsorption may be due to reduced
fructose absorption by enterocytes, impaired enteric microbiome, and decreased
intestinal permeability.
PMID- 26426643
TI - Etiology and Antimicrobial Susceptibility Pattern of Pathogenic Bacteria in
Children Subjected to UTI: A Referral Hospital-Based Study in Northwest of Iran.
AB - Urinary tract infection (UTI) is 1 of the most common bacterial diseases in
children with a considerable resistance to antimicrobials. This 5 years
prospective study was carried out to determine the frequency of isolation and
antimicrobial resistance patterns of uropathogens among children subjected to
urine culture at Tabriz Children Educational-Health Care Center, in the northwest
of Iran. Organisms were isolated using standard culture techniques. Frequency of
UTI among children examined by urine culture was 3.6%. The isolated bacteria were
Escherichia coli (71.4%), followed by Klebsiella spp. (9.6%), Enterococcus spp.
(6.4%), Pseudomonas aeruginosa (4.2%), Serratia spp. (4.2%), and Enterobacter
spp. (4.2%). E coli resistance levels were 11% for nitrofurantoin, 15% for
ciprofloxacin, 25% for nalidixic acid, and 30% to 75% for amikacin, gentamicin,
ceftriaxone, ceftizoxime, cefotaxime, and co-trimoxazole. Among the tested
antibiotics, ciprofloxacin, showed the highest activity (100%) against Klebsiella
and P aeruginosa isolates followed by amikacin, nalidixic acid, and gentamicin.
Overall, the highly active antibiotic against Gram-negative and Gram-positive
organisms was amikacin and then ciprofloxacin. On the other hand, the empirical
initial therapy with co-trimoxazole and third-generation cephalosporins would be
inadequate for more cases of UTI in the study area. Moreover, susceptibility
testing should be carried out on all clinical isolates, and the empirical
antibiotic treatment changed accordingly.
PMID- 26426644
TI - Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and
Delivery in a Woman With Panhypopituitarism: Case Report and Review.
AB - Hypopituitarism is defined as the partial or complete defect of anterior
pituitary hormone secretion. Patients with hypopituitarism usually need life-long
hormone replacement therapy. However, in this case, we report a patient with
panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was
completely recovered after pregnancy and delivery. In this case study, we
reported the case management and conducted a review of literature to identify the
possible mechanism of pituitary function recovery. The patient who suffered from
secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the
hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin
were at normal range. After surgical removal of the tumor which invasion in the
sellar region, the patient had panhypopituitarism confirmed by the routine
hormone test. Though spontaneous pregnancy is impossible in female patients with
panhypopituitarism, the patient was restored fertility by the help of artificial
reproductive techniques. After the confirmation of the pregnancy, levothyroixine
was increased to 75 MUg daily and readjusted to 150 MUg daily before delivery
according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily
replaced cortisone acetate; the dose was increased according to the symptoms of
morning sickness. A single stress dose of hydrocortisone (200 mg) was used before
elective cesarean delivery and was tapered to the dose of 10 mg per day in 1
week. Levothyroixine was reduced to 75 MUg daily after delivery. During follow
up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely
recovered. The peak serum cortisol level could increase to 19.08 MUg/dL by
insulin-induced hypoglycemia. However, growth hormone remained unresponsive to
the insulin-tolerance test, and thyroid hormone still needed exogenous
supplementation. Hormone replacement therapy needed closely followed by
endocrinologist and multidisciplinary cooperation during the pregnancy of
patients with hypopituitarism. This case indicates that the pituitary function
may partially recover after pregnancy in panhypopituitarism patients.
PMID- 26426645
TI - Interface Fluid Syndrome Induced by Uncontrolled Intraocular Pressure Without
Triggering Factors After LASIK in a Glaucoma Patient: A Case Report.
AB - This study sought to describe a glaucoma patient with interface fluid syndrome
(IFS) induced by uncontrolled intraocular pressure (IOP) without triggering
factors after laser in situ keratomileusis (LASIK). Case report and review of the
literature. A 23-year-old man with open-angle glaucoma underwent bilateral LASIK
for myopia in 2009. Two years later, the patient reported sudden vision loss. The
IOP in the right eye was not measurable using Goldmann applanation tonometry
(GAT), but was determined to be 33.7 mm Hg using a noncontact tonometer. IFS was
diagnosed based on the presence of space-occupying interface fluid on anterior
segment optical coherence tomography images. After a trabeculectomy was
performed, the IOP decreased to 10 mm Hg, and GAT measurement became possible.
However, the corneal fold remained visible in the flap interface. Six months
later, the IOP in the left eye increased, and a trabeculectomy was performed
during the early stages of this increase in IOP. Following this procedure, the
IOP decreased, and visual acuity remained stable. In glaucoma cases that involve
a prior increase in IOP, IOP can continue to increase during the disease course
even if temporary control of IOP has been achieved. If LASIK is performed in such
cases, the treatment of glaucoma becomes insufficient because of underestimation
of the typical IOP. In fact, the measurement of IOP can become difficult because
of high-IOP levels. Therefore, LASIK should not be performed on patients with
glaucoma who are at high risk of elevated IOP.
PMID- 26426646
TI - Novel Therapy for Primary Canaliculitis: A Pilot Study of Intracanalicular
Ophthalmic Corticosteroid/Antibiotic Combination Ointment Infiltration.
AB - In patients with primary canaliculitis, conservative medical therapy is
associated with a high recurrence rate. Surgical treatments carry a great
resolution rate but sometimes can result in the lacrimal pump dysfunction and
canalicular scarring. The aim of this study is to introduce a minimally invasive
approach, intracanalicular ophthalmic corticosteroid/antibiotic combination
ointment infiltration (IOI, intracanalicular ointment infiltration), and to
report our preliminary results for treating primary canaliculitis. In this
retrospective, interventional case series, 68 consecutive patients with newly
developed primary canaliculitis at a major tertiary eye center between January
2012 and January 2015. Thirty-six patients received conservative medical
treatment alone (group 1; 36 eyes). Twenty-two patients and 10 medically
uncontrolled patients from group 1 underwent IOI therapy (group 2; 32 eyes). Ten
patients and 26 recurrent patients from group 1 and group 2 underwent surgery
(group 3; 36 eyes). Patients were followed-up for at least 8 weeks. Clinical
characteristics and outcomes were analyzed and compared. In this study, patients'
age, sex, onset location, and durations of disease among 3 groups showed no
significant difference. The resolution rate in group 2 was 72.7% (16/22) for new
patients and 68.8% (22/32) for gross patients, respectively, both of which are
higher than that of group 1 (22.2%, 10/36) but lower than that of group 3 (100%,
36/36). Of group 3, 2 patients received 2 surgical interventions and resolved
finally. Microbiological workup was available in 51 patients. The most common
isolates were staphylococcus species (27.9%) and streptococcus species (20%).
Canalicular laceration developed in 1 patient during the IOI procedure and 1
patient undergoing surgery. Only 2 had postoperative lacrimal pump dysfunction
and 1 had canalicular scarring in group 3. The IOI may be an effective and
minimally invasive technique for treating primary canaliculitis and obviate the
need for further intensive surgery.
PMID- 26426647
TI - The Expanding Burden of Elevated Blood Pressure in China: Evidence From Jiangxi
Province, 2007-2010.
AB - Elevated blood pressure (BP) as a risk factor accounts for the biggest burden of
disease worldwide and in China. This study aimed to estimate attributed mortality
and life expectancy (LE) to elevated BP in Jiangxi province between 2007 and
2010. BP and mortality data (2007 and 2010 inclusive) were obtained from the
National Chronic Diseases and Risk Factors Surveillance Survey and Disease
Surveillance Points system, respectively. Population-attributable fraction used
in comparative risk assessment of the Global Burden of Disease study 2010 were
followed to quantify the attributed mortality to elevated BP, subsequently life
table methods were applied to estimate its effects on LE. Uncertainty analysis
was conducted to get 95% uncertainty intervals (95% uncertainty interval [UI])
for each outcome. There are 35,482 (95% UI: 31,389-39,928) and 47,842 (42,323
53,837) deaths in Jiangxi province were caused by elevated BP in 2007 and 2010,
respectively. 2.24 (1.87-2.65) years of LE would be gained if all the attributed
deaths were eliminated in 2007, and increased to 3.04 (2.52-3.48) in 2010. If the
mean value of elevated BP in 2010 was decreased by 5 and 10 mm Hg, 5324 (4710
5991) and 11,422 (10,104-12,853) deaths would be avoided, with 0.41 (0.37-0.48)
and 0.85 (0.71-1.09) years of LE gained, respectively. The deaths attributable to
elevated BP in Jiangxi province has increased by 35% from 2007 to 2010, with 0.8
years of LE loss, suggesting the necessity to take actions to control BP in
Chinese population.
PMID- 26426648
TI - Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A
Prospective Observational Study.
AB - Despite numerous studies, there has been little progress in the use of biomarkers
for predicting treatment response in patients with tuberculosis (TB). Patients
with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively
recruited. Blood samples were taken upon diagnosis and 2 months after the start
of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen
stimulated cytokines was conducted to select potential biomarkers for further
testing. Outcome was defined as persistent culture positivity at 2 months into
treatment. Of 167 enrolled patients, 26 had persistent culture positivity.
RANTES, IL-22, MMP-8, IL-18, MIG, and Granzyme A were selected as potential
biomarkers. For predicting persistent culture positivity, receiver-operating
characteristics (ROC) analysis showed that initial RANTES (AUC: 0.725 [0.624
0.827]) and 2-month MMP-8 (AUC: 0.632 [0.512-0.713]) had good discriminative
ability. Using a logistic regression model, low initial RANTES level (< 440
pg/mL), initial smear positivity, and high 2-month MMP-8 level (> 3000 pg/mL)
were associated with persistent culture positivity. Low initial RANTES level and
initial smear positivity had a positive predictive value of 60% (12/20) for
persistent culture positivity, compared with 4% (3/75) among patients with high
RANTES level and smear negativity upon diagnosis. In the 72 patients with either
low RANTES/smear negativity or high RANTES/smear positivity upon diagnosis, the 2
month MMP-8 level had a positive and negative predictive value of 24 and 94%,
respectively, for 2-month culture status. Aside from an initial sputum smear
status, serum RANTES level at diagnosis and MMP-8 level at 2 months of treatment
may be used to stratify risk for culture persistence.
PMID- 26426649
TI - Effectiveness of Prior Use of Beta-Blockers for Preventing Adverse Influences of
Severe Hypoglycemia in Patients With Diabetes: An Observational Study.
AB - The study aimed to identify predictors of severe acute hypertension (>= 180/110
mmHg) during severe hypoglycemia and to assess the efficacy of prior use of
catecholamine-blocking agents for preventing adverse influences in diabetic
patients with severe hypoglycemia. We performed a retrospective study between
January 2006 and March 2012 to assess diabetic patients with severe hypoglycemia
at a single center in Japan. Severe hypoglycemia was defined as the presence of
any hypoglycemic symptoms that required the medical assistance of another person
after visiting the emergency room by ambulance. Multivariate logistic regression
analysis was performed to identify possible predictors of severe hypertension due
to severe hypoglycemia and to assess whether prior use of alpha- or beta-blockers
is beneficial for the prevention of severe hypertension in diabetic patients with
severe hypoglycemia. Multivariate adjustments were made for age, sex, preexisting
hypertension, history of ischemic heart disease, blood glucose level upon
arrival, estimated GFR, and prior use of alpha- or beta-blockers. A total of
59,602 patients who visited the emergency room were screened and 352 diabetic
patients with severe hypoglycemia were enrolled. Incidences of severe
hypertension before and at 3 and 6 hours after the initiation of antihypoglycemic
treatment were 21.3%, 6.7%, and 0% in patients with type 1 diabetes (n = 61) and
38.8%, 18.2%, and 8.2% in patients with type 2 diabetes (n = 291), respectively.
Aging was positively (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.00
1.03; P = 0.02) and female sex was negatively (OR, 0.50; 95% CI, 0.29-0.86; P =
0.01) associated with occurrence of severe hypertension during severe
hypoglycemia. In addition, prior use of beta-blockers was negatively associated
with occurrence of severe hypertension during severe hypoglycemia using
multivariate logistic regression analysis (OR, 0.31; 95% CI, 0.11-0.83; P =
0.02). None of the patients with prior use of beta-blockers had hypokalemia (<3.0
mEq/L). Prior use of beta-blockers may prevent adverse influences such as severe
hypertension and hypokalemia during severe hypoglycemia in diabetic patients.
PMID- 26426650
TI - Tumor-Infiltrating Immune Cells Are Associated With Prognosis of Gastric Cancer.
AB - Immune cells contribute to determining the prognosis of gastric cancer. However,
their exact role is less clear. We determined the prognostic significance of
different immune cells in intratumoral tissue (T), stromal tissue (S), and
adjacent normal tissue (N) of 166 gastric cancer cases and their interactions,
including CD3+, CD4+, CD8, CD57+, CD68+, CD66b+, and Foxp3+ cells, and
established an effective prognostic nomogram based on the immune reactions. We
found high densities of TCD3+, TCD4+, TCD8+, SCD3+, SCD4+, SCD57+, SCD66b+, and
NFoxp3+ cells, as well as high TCD8+/SCD8+ ratio, TCD68+/SCD68+ ratio,
TCD3+/TFoxp3+ ratio, TCD4+/TFoxp3+ ratio, TCD8+/TFoxp3+ ratio, SCD3+/SFoxp3+
ratio, and SCD4+/SCD8+ ratio were associated with better survival, whereas high
densities of TCD66b+, TFoxp3+, SFoxp3+ and NCD66b+ cells as well as high
TCD57+/SCD57+ ratio, TCD66b+/SCD66b+ ratio, SCD8+/SFoxp3+ ratio, and
TFoxp3+/NFoxp3+ ratio were associated with significantly worse outcome.
Multivariate analysis indicated that tumor size, longitudinal tumor location, N
stage, TCD68+/SCD68+ ratio, TCD8+/TFoxp3+ ratio, density of TFoxp3+ cells, and
TCD66b+/SCD66b+ ratio were independent prognostic factors, which were all
selected into the nomogram. The calibration curve for likelihood of survival
demonstrated favorable consistency between predictive value of the nomogram and
actual observation. The C-index (0.83, 95% CI: 0.78 to 0.87) of our nomogram for
predicting prognosis was significantly higher than that of TNM staging system
(0.70). Collectively, high TCD68+/SCD68+ ratio and TCD8+/TFoxp3+ ratio were
associated with improved overall survival, whereas high density of TFoxp3+ cells
and TCD66b+/SCD66b+ ratio demonstrated poor overall survival, which are promising
independent predictors for overall survival in gastric cancer.
PMID- 26426651
TI - Comparison of Laparoscopic-Assisted Operations and Laparotomy Operations for the
Treatment of Hirschsprung Disease: Evidence From a Meta-Analysis.
AB - The purpose of this meta-analysis is to compare the relative merits among
laparoscopic-assisted operations and laparotomy operations for patients with
Hirschsprung disease. PubMed, Web of Science, and Wanfang databases were searched
for the related articles. We analyzed dichotomous variables by estimating odds
ratios (ORs) with their 95% confidence intervals (CIs) and continuous variables
using the weighted mean difference (WMD) with the 95% CI. The random-effects
model (REM) was used to combine the results. The outcome measures included
operating time (OT), estimated blood loss (EBL), length of hospital stay (LOHS),
mean first bowel movement (MFBM), and number of complications. Sixteen articles
were included in the meta-analysis. These studies involved a total of 774
patients, 396 of whom underwent laparoscopic-assisted operations and 378 of whom
underwent laparotomy operations. The EBL (WMD = -1.48, 95% CI = -1.82, -1.13),
LOHS (WMD = -0.67, 95% CI = -0.86, -0.49), MFBM (WMD = -0.83, 95% CI = -1.05,
0.61), and number of complications (OR = 0.60, 95% CI = 0.40, 0.89) were
significantly lower in laparoscopic-assisted operations than in laparotomy
operations. The OT (WMD = 0.12, 95% CI = -0.05, 0.28) showed no significant
differences between laparoscopic-assisted operations and laparotomy operations.
Compared with laparotomy operations, laparoscopic-assisted operations are
generally safer and more reliable for patients with Hirschsprung disease.
PMID- 26426652
TI - The Risk of Epithelial Ovarian Cancer of Women With Endometriosis May be Varied
Greatly if Diagnostic Criteria Are Different: A Nationwide Population-Based
Cohort Study.
AB - This article aims to test the hypothesis that the risk of epithelial ovarian
cancer (EOC) in women with endometriosis might be changed by enrolling different
population. A nationwide 14-year historic cohort study using the National Health
Insurance Research Database (NHIRD) of Taiwan and the Registry for Catastrophic
Illness Patients was conducted. A total of 239,385 women aged between 20 and 51
years, with at least 1 gynecologic visit after 2000, were analyzed. Cases
included women with a diagnosed endometriosis, which was established along a
spectrum from at least 1 medical record of endometriosis (recalled endometriosis)
to tissue-proved ovarian endometriosis (n = X). Controls included women without
any diagnosis of endometriosis (n = 239,385 - X). We used Cox regression, and
computed hazard ratios (HRs) with 95% confidence intervals (95% CI) to determine
the risk of EOC in patients. The EOC incidence rates (IRs, per 10,000 person
years) of women with endometriosis ranged from 1.90 in women with recalled
endometriosis to 18.70 in women with tissue-proved ovarian endometrioma, compared
with those women without any diagnosis of endometriosis (0.77-0.89), contributing
to crude HRs ranging from 2.59 (95% CI, 2.09-3.21; P < 0.001) to 24.04 (95% CI,
17.48-33.05; P < 0.001). After adjustment for pelvic inflammatory disease,
infertility, Charlson co-morbidity index, and age, adjusted HRs were ranged from
the lowest of 1.90 (95% CI, 1.51-2.37; P < 0.001) in recalled endometriosis to
the highest of 18.57 (95% CI, 13.37-25.79; P < 0.001) in tissue-proved ovarian
endometrioma, which was inversely related to the prevalence rate of endometriosis
(from the highest of 30.80% in recalled endometriosis to the lowest of 1.54% in
tissue-proved ovarian endometrioma). The risk of EOC in women with endometriosis
varied greatly by different criteria used. Women with endometriosis might have a
more apparently higher risk than those reported by systematic review and meta
analysis.
PMID- 26426653
TI - TIPE2 mRNA Level in PBMCs Serves as a Novel Biomarker for Predicting Short-Term
Mortality of Acute-on-Chronic Hepatitis B Liver Failure: A Prospective Single
Center Study.
AB - It remains difficult to accurately predicate short-term mortality of acute-on
chronic hepatitis B liver failure (ACHBLF). Tumor necrosis factor-alpha-induced
protein 8-like 2 (TIPE2) is a novel identified negative regulator of immune
response and we have previously demonstrated TIPE2 play an essential role in the
pathogenesis of ACHBLF. We therefore aimed to evaluate the diagnosis value of
TIPE2 mRNA in peripheral blood mononuclear cells (PBMCs) for predicting 3-month
mortality of ACHBLF patients. This prospective study consisted of 108 ACHBLF
patients from March 2009 to May 2013 as training cohort and 63 ACHBLF patients
from June 2013 to December 2014 as validation cohort. Forty-two patients with
chronic hepatitis B (CHB) and 22 healthy volunteers were also included as
controls. The mRNA level of TIPE2 in PBMCs was determined using quantitative real
time polymerase chain reaction. Univariate analysis and Cox proportional hazard
regression analysis were performed to identify independent risk factors to 3
month mortality. Area under the receptor operating characteristic curve (AUROC)
was performed to assess diagnostic value of TIPE2 mRNA in training and validation
cohort. The level of TIPE2 mRNA was significantly higher in ACHBLF patients
(median (interquartile): 6.5 [3.7, 9.6]) compared with CHB (2.3 [1.6, 3.7]) and
healthy controls (0.4 [0.3, 0.6]; both P < 0.05). Cox proportional hazards
regression analyses showed 5 independent risk factors associated with 3-month
mortality of ACHBLF: white blood cells (HR = 1.058, 95% CI: 1.023-1.095),
spontaneous bacterial peritonitis (HR = 2.541, 95% CI: 1.378-4.686), hepatic
encephalopathy (HR = 1.848, 95% CI: 1.028-3.321), model for end-stage liver
diseases (MELD) score (HR = 1.062, 95% CI: 1.009-1.118), and TIPE2 mRNA (HR =
1.081, 95% CI: 1.009-1.159). An optimal cut-off point 6.54 of TIPE2 mRNA showed
sensitivity of 74.63%, specificity of 90.24%, positive predictive value of 92.5%,
and negative predictive value of 67.3% for predicting 3-month mortality in
training cohort. Furthermore, TIPE2 mRNA plus MELD performed better than MELD
alone for predicting 3-month mortality in training (AUROC, 0.853 vs 0.722, P <
0.05) and validation cohort (AUROC, 0.909 vs 0.717, P < 0.001). TIPE2 mRNA level
might be a novel biomarker in predicting 3-month mortality of ACHBLF. Combination
of TIPE2 mRNA and MELD would improve the diagnostic value of MELD alone in
predicting 3-month mortality of patients with ACHBLF.
PMID- 26426654
TI - Lower Serum 25-Hydroxyvitamin D Level is Associated With 3 Types of Autoimmune
Thyroid Diseases.
AB - Autoimmune thyroid diseases (AITD) are common autoimmune disorders. A few studies
have analyzed the association between serum vitamin D levels and AITD, and
available data remain inconclusive. The aim of this study was to evaluate the
association between serum vitamin D levels and 3 types of AITD, that is Graves'
disease (GD), Hashimoto's thyroiditis (HT), and postpartum thyroiditis (PPT). Two
independent case-control studies were designed. The first is a cross-sectional
case-control study in which we examined the levels of 25(OH)D in patients with
newly diagnosed GD or HT and in controls; the second is a nested case-control
study in which we compared 25(OH)D levels in 610 women who developed PPT during
the follow-up after delivery and those who did not. Compared with the controls,
GD patients and HT patients had significantly lower 25(OH)D levels. PPT cases
also had a lower serum 25(OH)D concentration than controls. Serum 25(OH)D levels
were associated with neither antithyroid peroxidase antibody nor
antithyroglobulin antibody in GD and HT. There was no significant relationship
between thyroid-stimulating hormone and 25(OH)D levels. Every 5 nmol/L increase
in serum 25(OH)D concentrations was associated with a 1.55-, 1.62-, and 1.51-fold
reduction in GD, HT, and PPT risk, respectively. We observed a lower serum
vitamin D levels in AITD patients compared with controls. The lower the vitamin D
level is, not vitamin D deficiency per se, the higher the risk for developing
AITD will be. However, vitamin D does not have strong association with the titers
of thyroid antibodies or the levels of thyroid hormones.
PMID- 26426655
TI - Increased Risk of Chronic Sinusitis in Adults With Gastroesophgeal Reflux
Disease: A Nationwide Population-Based Cohort Study.
AB - Although gastroesophageal reflux disease (GERD) has been reported to coexist with
chronic rhinosinusitis (CRS), it remains controversial whether it increases risk
of CRS in adults. This study accesses risk of CRS in adults with newly diagnosed
GERD. We identified 15,807 adult patients with newly diagnosed GERD from Taiwan's
National Health Insurance Research Database for January 1, 2006 to December 31,
2009. We also randomly selected 47,421 subjects without this disease and matched
them with patients by age, sex, index year, and comorbidity to create a control
cohort. A Cox proportional hazards model was conducted to estimate the
development of CRS, including CRS without nasal polyps and CRS with nasal polyps.
Subjects were followed for a median of 2.12 years. In total, CRS developed in 964
(1.52%) of the subjects: 406 patients with GERD (2.57%) and 558 without it
(1.18%). After adjustment, those with GERD were found to have a 2.36 times
greater risk of CRS (95% confidence interval = 2.08-2.68; P < .001). Risk of this
CRS without nasal polyps was higher than the disease with polyps (adjusted hazard
ratio: 2.48 vs 1.85). The individuals with GERD in this study were at
significantly greater risk of CRS, most often without nasal polyps.
PMID- 26426656
TI - Statin Use Reduces Prostate Cancer All-Cause Mortality: A Nationwide Population
Based Cohort Study.
AB - Studies have suggested that statin use is related to cancer risk and prostate
cancer mortality. We conducted a population-based cohort study to determine
whether using statins in prostate cancer patients is associated with reduced all
cause mortality rates. Data were obtained from the Taiwan National Health
Insurance Research Database. The study cohort comprised 5179 patients diagnosed
with prostate cancer who used statins for at least 6 months between January 1,
1998 and December 31, 2010. To form a comparison group, each patient was randomly
frequency-matched (according to age and index date) with a prostate cancer
patient who did not use any type of statin-based drugs during the study period.
The study endpoint was mortality. The hazard ratio (HR) and 95% confidence
interval (CI) were estimated using Cox regression models. Among prostate cancer
patients, statin use was associated with significantly decreased all-cause
mortality (adjusted HR = 0.65; 95% CI = 0.60-0.71). This phenomenon was observed
among various types of statin, age groups, and treatment methods. Analyzing the
defined daily dose of statins indicated that both low- and high-dose groups
exhibited significantly decreased death rates compared with nonusers, suggesting
a dose-response relationship. The results of this population-based cohort study
suggest that using statins reduces all-cause mortality among prostate cancer
patients, and a dose-response relationship may exist.
PMID- 26426658
TI - Association of Sodium Excretion With Metabolic Syndrome, Insulin Resistance, and
Body Fat.
AB - Sodium intake was reported to be related to metabolic syndrome (MS). Although a
strong association between sodium intake and blood pressure (BP) has been
reported, the relationship between sodium intake and other components of MS is
unknown. An observational study of 18,146 adults in the Korea National Health and
Nutrition Examination Survey IV-V databases (2008-2011) was performed. Estimates
of 24-h sodium excretion were made from a single fasting urine sample. A
significant positive association was found between sodium excretion and systolic
BP and between sodium excretion and diastolic BP in participants with and without
hypertension after adjusting for multiple covariates (P < 0.001 for trend). The
relationship between triglyceride or glucose levels and sodium excretion was
linear (P < 0.005). In both men and women, a positive relationship between sodium
excretion and waist circumference and an inverse relationship between sodium
excretion and high-density lipoprotein were found (P <= 0.001). Body fat
percentage, body fat mass, and insulin level were positively related to sodium
excretion (P <= 0.001), and HOMA-IR was significantly associated with sodium
excretion (P < 0.05). The risk of MS was elevated 1.279-fold in the second
quartile of sodium excretion (95% CI, 1.088-1.504, P = 0.003), 1.479-fold in the
third quartile (95% CI, 1.262-1.734; P < 0.001), and 1.929-fold in the highest
quartile (95% CI 1.654-2.249, P < .001) compared with the lowest quartile.
Sodium intake is significantly associated with all components of MS, body fat,
and insulin resistance. Therefore, a high-salt diet is a significant risk factor
for MS.
PMID- 26426657
TI - Inverse Probability of Treatment Weighting Analysis of Upfront Surgery Versus
Neoadjuvant Chemoradiotherapy Followed by Surgery for Pancreatic Adenocarcinoma
with Arterial Abutment.
AB - Combined arterial resection during pancreatectomy can be a challenging treatment,
and outcome would be more favorable if the tumor becomes technically removable
from the artery. Neoadjuvant chemoradiotherapy (NACRT) is expected to achieve
locoregional control and enable margin-negative resection. To investigate the
effects of NACRT in patients with pancreatic adenocarcinoma (PDAC) which were
deemed borderline resectable through preoperative imaging due to abutment of the
major artery, including the superior mesenteric artery (SMA) or common hepatic
artery (CHA), but were still considered to be technically removable. In the
current study, comparisons were make between 71 patients who underwent upfront
surgery and 21 patients who underwent NACRT followed by surgery in the strategy
to preserve the artery, using unmatched and inverse probability of treatment
weighting analysis (UMIN000017115). Fifty patients in the upfront surgery group
and 18 in the NACRT group underwent curative resection (70% vs 86%, respectively;
P = 0.16). The results of the propensity score weighted logistic regressions
indicated that the incidences of pathological lymph node metastasis and a
pathological positive resection margin were significantly lower in the NACRT
group (odds ratio, 0.006; P < 0.001 and odds ratio, 0.007; P < 0.001,
respectively). Among the propensity-score matched patients, the estimated 1- and
2-year survival rates in the upfront surgery group were 66.7% and 16.0%,
respectively, and those in the NACRT group were 80.0% and 65.2%, respectively. In
conclusion, it was suggested that chemoradiotherapy followed by surgery provided
clinical benefits in patients with PDACs in contact with the SMA or CHA.
PMID- 26426659
TI - Comparison of Efficacy Between Endoscopic Cyclophotocoagulation and Alternative
Surgeries in Refractory Glaucoma: A Meta-analysis.
AB - Refractory glaucoma refers to uncontrolled intraocular pressure (IOP) despite
anti-glaucoma medication and surgical treatment, which remains a challenge to be
treated. The objective of this study is to evaluate and statistically compare the
clinical efficacy between endoscopic cyclophotocoagulation (ECP) and alternative
surgical techniques in the treatment of refractory glaucoma in this article, as a
meta-analysis. Data sources are China Biomedical Database (Sinomed, online
version), China National Knowledge Infrastructure (CNKI), Cqvip, Wanfang
database, and PubMed. The randomized controlled trial (RCT) and case-control
study literatures evaluating the clinical efficacy between ECP and other surgical
techniques were searched electronically from public databases. The methodology
quality of the retrieved articles was evaluated according to the RCT or case
control study criteria. The success rate of treatment, intraocular pressure (IOP)
and visual acuity were statistically compared. RevMan 5.3 software was used for
the meta-analysis. In total, 6 relevant control studies were selected in this
study with a total sampling of 429 cases (429 eyes), including 204 eyes in the
ECP group and 225 in the non-ECP group. Meta-analysis demonstrated that the
clinical efficacy did not significantly differ between 2 groups (P > 0.05).
Postoperative IOP was dramatically reduced in both groups. However, it was
difficult to evaluate the combined influence of ECP and non-ECP therapies upon
IOP reduction. In conclusion, ECP and non-ECP treatment yielded almost equivalent
clinical efficacy in treating refractory glaucoma. The IOP-lowering degree,
safety, and incidence of complications remain to be further elucidated by RCTs
with a larger sample size.
PMID- 26426660
TI - Predicting of Venous Thromboembolism for Patients Undergoing Gynecological
Surgery.
AB - The purpose of this study was to determine the risk stratification of deep venous
thrombosis (DVT) in patients undergoing gynecological surgery. A retrospective
study was conducted with a cohort of 739 consecutive female patients undergoing
gynecological surgery between May 2008 and July 2013 in Beijing Chao-yang
hospital. DVT of the leg was detected using complete compression and color
Doppler ultrasound. Pulmonary embolism (PE) was diagnosed by computed tomography
pulmonary angiogram (CTPA). The overall incidence of DVT was 9.20% (68/739) in
this patient population, including 16 (2.17%) symptomatic DVT and 52 (7.04%)
silent DVT. A total of 66 (97.06%) DVT events were found within 7 days of surgery
and 2 (2.94%) after 1 week. 94.82% thrombi were located in distal vein, and the
rest 5.18% located in proximal and distal veins. Among the 68 patients with DVT,
46 patients with suspected PE received CTPA and 21 (45.65%) were confirmed with
PE. Six independent factors including varicose vein, bed rest time >= 48 h,
length of operation >= 3 h, laparotomy surgery, hypertension, and age >= 50 years
significantly increased the incidence of postoperative DVT on multivariate
analysis. Patients with none risk factor are at low risk, with 1 or 2 risk
factors are at moderate risk, and with >= 3 factors are at high risk of DVT. The
incidence of postoperative DVT and PE after gynecological surgery is high in
patients with moderate or high-risk level. Noninvasive detection of DVT in 7 days
after surgery is necessary because most patients showed no typical symptoms.
Appropriate prophylaxis could be performed in patients at moderate or high risk
of DVT.
PMID- 26426661
TI - Application of Onyx for Renal Arteriovenous Malformation With First Case Report
of a Renal Hyperdense Striation Sign: A CARE-Compliant Article.
AB - Onyx is an emerging treatment modality for visceral vascular malformations,
especially in cases in which delicate nidal penetration of the arteriovenous
malformation (AVM) is desired. A computed tomography (CT) image presentation of
hyperdense striations along the renal medulla secondary to the tantalum powder
has not been previously reported. A 65-year-old woman presented to our
institution with intermittent gross hematuria and left flank pain for 10 days.
Both CT and conventional angiographies confirmed cirsoid-type renal AVM, which
was successfully treated with Onyx. Follow-up CT after treatment revealed
presence of hyperdense striations along the renal medulla, which resolved during
later image follow-up. Despite its frequent usage in neural intervention, the
application of Onyx in visceral AVM is gradually gaining interest, especially in
cases in which delicate nidal penetration of the AVM is desired. Renal hyperdense
striation sign should be recognized to avoid confusion with embolizer migration,
and further studies in patients with renal function impairment may be helpful in
understanding its influence of renal function.
PMID- 26426662
TI - Risk-Factor Profile and Comorbidities in 2398 Patients With Newly Diagnosed
Hypertension From the Abuja Heart Study.
AB - Risk factors, comorbidities, and end-organ damage in newly diagnosed hypertension
(HT) are poorly described in larger cohorts of urban African patients undergoing
epidemiological transition. We therefore decided to characterize a large cohort
of hypertensive subjects presenting to a tertiary health center in sub-Saharan
Africa. It is an observational cross-sectional study. We prospectively collected
detailed clinical, biochemical, electrocardiography, and echocardiography data of
all subjects with HT as the primary diagnosis in patients presenting at the
Cardiology Unit of the University of Abuja Teaching Hospital over an 8-year
period. Of 2398 subjects, 1187 patients (49.4%) were female with a mean age of 51
+/- 12.8 years. Presenting symptoms and signs were most commonly palpitation in
691 (28.8%) followed by dyspnoea on exertion in 541 (22.6%), orthopnea in 532
(22.2%), pedal oedema in 468 (19.5%), paroxysmal nocturnal dyspnoea in 332
(13.8%), whereas only 31 (1.3%) presented with chest pain. Risk factors were
obesity in 671 (28%); 523 (21.8%) had total cholesterol >5.2 mmol/L, diabetes
mellitus was present in 201 (8.4%) and 187 (7.8%) were smokers. End-organ damage
was present in form of echocardiographic left ventricular hypertrophy in 1336
(55.7%) followed by heart failure in 542 (22.6%). Arrhythmias occurred in 110
(4.6%) of cases, cerebrovascular accident in 103 (4.3%), chronic kidney disease
in 26 (1.1%), hypertensive encephalopathy in 10 (0.4%), and coronary artery
disease in 6 (0.26%). There were marked differences in sex as women were more
obese and men presented with more advanced disease. The burden of HT and its
complications in this carefully characterized African cohort is quite enormous
with more than three-fourth having one form of complication. The need of
effective primary and secondary preventive measures to be mapped out to tackle
this problem cannot be overemphasized.
PMID- 26426663
TI - A Case Report of Gastrointestinal Hemorrhage and Perforation During Apatinib
Treatment of Gastric Cancer.
AB - Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial
growth factor receptor-2, which shows good efficacy and safety in clinical trials
for chemotherapy-refractory gastric cancer patients. Till now, there is no case
report after apatinib came in the market. We presented a 55-year-old Chinese
woman with advanced gastric cancer, who received apatinib after failure of second
line chemotherapy. On the 19th day of apatinib administration, she suffered from
gastrointestinal hemorrhage. Then, her condition rapidly deteriorated to
gastrointestinal perforation. Although the patient received timely medical and
surgical treatment, she finally died of septic shock. Although apatinib shows
exciting efficacy and good tolerance in phase II and III clinical trials, this
novel targeted drug should be prescribed carefully and close clinical monitoring
is needed when using it.
PMID- 26426664
TI - Comparative Treatment Failure Rates of Respiratory Fluoroquinolones or beta
Lactam + Macrolide Versus beta-Lactam Alone in the Treatment for Community
Acquired Pneumonia in Adult Outpatients: An Analysis of a Nationally
Representative Claims Database.
AB - No comparative effectiveness study has been conducted for the following 3
antibiotics: respiratory fluoroquinolones, beta-lactam, and beta-lactam +
advanced macrolide. To gain insights into the real-world clinical effectiveness
of these antibiotics for community-acquired pneumonia in adult outpatients, our
study investigated the treatment failure rates in 2 million representative
participants from the National Health Informatics Project (NHIP) of Taiwan. A new
user cohort design was used to follow NHIP participants from January 2000 until
December 2009. Treatment failure was defined by either one of the following
events: a second antibiotic prescription, hospitalization due to CAP, an
emergency department visit with a diagnosis of CAP, or 30-day nonaccident-related
mortality. From 2006 to 2009, we identified 9256 newly diagnosed CAP outpatients,
1602 of whom were prescribed levofloxacin, 2100 were prescribed moxifloxacin,
5049 were prescribed beta-lactam alone, and 505 were prescribed advanced
macrolide + beta-lactam. Compared with the beta-lactam-based regimen, the
propensity score-matched odds ratio for composite treatment failure was 0.81 (95%
CI, 0.67-0.97) for moxifloxacin, 1.10 (95% CI, 0.90-1.35) for levofloxacin, and
0.95 (95% CI, 0.67-1.35) for macrolide +beta-lactam. Moxifloxacin was associated
with lower treatment failure rates compared with beta-lactam alone, or
levofloxacin in Taiwanese CAP outpatients. However, due to inherent limitations
in our claims database, more randomized controlled trials are required before
coming to a conclusion on which antibiotic is more effective for Taiwanese CAP
outpatients. More population-based comparative effectiveness studies are also
encouraged and should be considered as an integral piece of evidence in local CAP
treatment guidelines.
PMID- 26426665
TI - Steroid Administration is Effective to Prevent Strictures After Endoscopic
Esophageal Submucosal Dissection: A Network Meta-Analysis.
AB - Esophageal stricture is a severe adverse event after circumferential endoscopic
submucosal dissection (ESD). Steroid administration is a new method to prevent
stricture formation. We performed a meta-analysis to investigate the efficacy and
safety of steroid administration to prevent esophageal stricture after
circumferential ESD. PubMed, the Cochrane Library, EMBASE, Chinese Biomedical
Database, and Clinicaltrials.gov were searched. Studies on steroid administration
+ endoscopic balloon dilation (EBD) versus EBD alone for esophageal stricture
were included and pooled analyzed in random-effects models. Besides, subgroup
analysis and network analysis were performed to define the influence of ESD type
and steroid administration method. Twelve studies involving 513 patients were
included. Meta-analysis showed that steroid administration significantly achieved
a lower stricture rate (risk ratio [RR], 0.40; 95% CI, 0.20-0.81) and less
required EBD sessions (mean difference [MD], -4.33; 95% CI, -6.10 to -2.57) than
control. Subgroup analysis indicated that steroid was effective after both semi-
and complete circumferential ESD. Network meta-analysis showed that compared with
oral steroid, local injected steroid had a similar effect to prevent stricture
(RR, 1.16; 95% CI, 0.48-2.85), whereas a better effect to reduce required EBD
sessions (MD, 7.77; 95%CI, 0.26-15.3). Additional steroid administration is
effective to reduce the stricture rate and required EBD sessions. And local
injected steroid was superior to oral steroid in EBD reduction, whereas due to
the varied method and dose of steroid administration, the finding needs to be
clarified in the future.
PMID- 26426667
TI - Massive Lumbosacral Subcutaneous Exudate After Surgical Treatment of a Large
Lipomyelocele: Case Report and Literature Review.
AB - Lipomyelocele is an uncommon type of lipoma that occurs with spina bifida. We
present the clinical course and therapeutic process of a female who underwent
resection of a lipomyelocele and developed a massive lumbosacral subcutaneous
exudate postoperatively. The therapeutic process is described in detail, and a
review of the relevant literature on lipomyelocele is presented. A 23-year-old
woman presented to our institution complaining of a large lumbosacral
subcutaneous mass. She underwent surgical resection of the mass and untethering
of the spinal cord under intraoperative neurophysiologic monitoring. A massive
lumbosacral subcutaneous exudate developed postoperatively. After excluding
cerebrospinal fluid (CSF) leakage, we placed a suction drain. Written informed
consent was obtained from the patient for publication of this case report and any
accompanying images. A copy of the written consent is available for review by the
editor of this journal. Because of this, there is no need to conduct special
ethic review and the ethical approval is not necessary. Postoperative pathologic
examination confirmed the diagnosis of lipomyelocele. Continuation of the
negative-pressure drain for 1 week yielded >1000 mL of fluid. The patient
recovered well and developed no further subcutaneous exudate. In a patient with
massive lumbosacral subcutaneous exudate after surgical treatment of a large
lipomyelocele, continuous negative-pressure drainage can be an effective
treatment method after excluding CSF leakage.
PMID- 26426668
TI - Cyclophilin A in Ruptured Intracranial Aneurysm: A Prognostic Biomarker.
AB - Cyclophilin A (CyPA), an oxidative stress-induced factor, was found to play an
important role in the aneurysm formation. Our working hypothesis was that the
plasma level of CyPA in ruptured intracranial aneurysm could predict the
neurological outcome. From 2011 to 2013, a total of 36 patients with ruptured
saccular intracranial aneurysm were recruited in our study. Before coil
embolization, we draw blood samples at the orifice of a culprit aneurysm and in
the remote peripheral vein for measurements of the CyPA levels. We utilized the
modified Rankin scale 30 days after aneurysm rupture as the outcome measure.
Generalized linear models were used to estimate the adjusted odds ratios of the
poor neurological outcome given the presence of high plasma level of CyPA. The
aneurysmal and venous CyPA levels were significantly associated with the initial
clinical severity (P = 0.004 and 0.03, respectively) and 30-day outcome (P = 0.01
and 0.02, respectively). The aneurysmal CyPA levels modestly correlated with age
and high Fisher grade (rho = 0.39 and 0.41; P = 0.02 and 0.01, respectively). The
aneurysmal CyPA levels strongly correlated with the venous counterpart (rho =
0.89; P < 0.001). Patients with high levels of aneurysmal CyPA were 15.66 times
(95% CI, 1.48-166.24; P = 0.02) more likely to have worse neurological outcome
than those with the low levels after adjustment of the age, gender, and the
documented confounding factors. High plasma level of CyPA is a significant
prognostic biomarker for poor neurological outcome in patients with ruptured
intracranial aneurysm.
PMID- 26426666
TI - Comparative Effectiveness of First Antiretroviral Regimens in Clinical Practice
Using a Causal Approach.
AB - The objective of this study was to estimate the cumulative incidences of failure
by months 12 (M12) and 24 (M24) for the most prescribed first-line anti
retroviral regimens (ART). It is retrospective analysis of a prospectively
collected database. All patients who initiated their first ART with the most
prescribed regimens between 1st January 2004 and 30th June 2013 in 12 large HIV
reference centers in France were included. The outcome was treatment failure-
defined by any treatment modification for virological or tolerability reasons-
and comparisons between regimens were carried out at M12 and M24. Adjusted and
weighted methods via the propensity score (PS) were used to compare the
effectiveness of the first antiretroviral regimens. Potential confounders of the
treatment-outcome association were used to estimate PS with multinomial logistic
regression. Overall, 3128 and 2690 patients were included in the M12 and M24
analyses, respectively. Patients received 5 different regimens (ABC/3TC with
ATV/r or DRV/r, TDF/FTC with ATV/r, DRV/r, or EFV). Failure was reported in 25%
and 42% at M12 and M24, respectively. Patients who received TDF/FTC/EFV had a
significantly higher proportion of failure at M12 by comparison with TDF/FTC with
DRV/r (reference), but not at M24. Patients in the 3 other groups had a trend
toward a higher proportion of failure at M12 although not statistically
significant. No difference was found at M24. Using data from a large prospective
cohort, we found that boosted atazanavir and darunavir had comparable
effectiveness, whatever the associated NRTIs, whereas efavirenz-based regimens
were relatively less performing on the short term.
PMID- 26426669
TI - Tibial Tuberosity Avulsion Fracture and Open Proximal Tibial Fracture in an
Adult: A Case Report and Literature Review.
AB - A displaced tibial tuberosity avulsion fracture associated with an open extra
articular proximal tibial diaphyseal fracture is an uncommon fracture pattern.
This case report describes the successful management of such a fracture pattern
in a 45-year old male using an open reduction and lag screw fixation of the
tuberosity with a minimally invasive reduction and plate fixation of the proximal
tibial diaphyseal fracture. A literature search was done to determine the
expected clinical outcome of this fracture pattern. This is the first reported
adult case of an avulsion fractures of the tibial tuberosity associated with an
open proximal tibial diaphyseal fracture successfully treated by an anatomical
reduction and fixation of the avulsion fracture of the tibial tuberosity combined
with minimally invasive percutaneous plate osteosynthesis of the proximal tibial
diaphyseal fractures.
PMID- 26426670
TI - Hypokalemic Paralysis Complicated by Concurrent Hyperthyroidism and Chronic
Alcoholism: A Case Report.
AB - Thyrotoxic periodic paralysis (TPP) is characterized by the presence of muscle
paralysis, hypokalemia, and hyperthyroidism. We report the case of a young man
with paralysis of the lower extremities, severe hypokalemia, and concurrent
hyperthyroidism. TPP was suspected; therefore, treatment consisting of judicious
potassium (K+) repletion and beta-blocker administration was initiated. However,
urinary K+ excretion rate, as well as refractoriness to treatment, was
inconsistent with TPP. Chronic alcoholism was considered as an alternative cause
of hypokalemia, and serum K+ was restored through vigorous K repletion and the
addition of K+ -sparing diuretics. The presence of thyrotoxicosis and hypokalemia
does not always indicate a diagnosis of TPP. Exclusion of TPP can be accomplished
by immediate evaluation of urinary K+ excretion, acid-base status, and the amount
of potassium chloride required to correct hypokalemia at presentation.
PMID- 26426671
TI - Strain Lattice Imprinting in Graphene by C60 Intercalation at the Graphene/Cu
Interface.
AB - Intercalation of C60 molecules at the graphene-substrate interface by annealing
leads to amorphous and crystalline structures. A comparison of topography and
electronic structure with wrinkles and moire patterns confirms intercalation. The
intercalated molecules imprint a local strain/deformation on the graphene layer
whose magnitude is controlled by the intermolecular distance. The crystalline
intercalated structure exhibits a superlattice peak in the local density of
states. This work provides control of local strain in graphene.
PMID- 26426675
TI - Enhancement of heat conduction in carbon nanotubes filled with fullerene
molecules.
AB - Heat conduction in carbon nanopeapods (CNPs), i.e. carbon nanotubes (CNTs) filled
with fullerene C60 molecules, is investigated using molecular dynamics
simulations. The enhancement mechanisms of CNP thermal conductivity, compared
with bare CNTs, are discussed via the local heat flux onto a single atom, the
relative contributions of different phonon oscillation frequencies to thermal
conductivity and the phonon vibrational density of states. The result shows that
filled C60 can increase the CNT thermal conductivity by up to 9.6 times in the
temperature range of 100-500 K. The constructive phonon mode couplings between
the tube and C60 in a frequency range of 0-20 THz, especially in x-, y-direction
transverse acoustic modes and the radial breath mode, are primarily responsible
for the increment of thermal conductivity. In addition, filled C60 molecules in
CNPs enhance the mass transfer contribution to the total heat flux. This
contribution accounts for 22-58% in CNPs, much higher than 12% in CNTs. With the
temperature going up, the phonon scattering increases and the contribution from
mass transfer to total heat flux decreases. Therefore, the CNP thermal
conductivity decreases with rising temperature. This study sheds lights on
nanoscale thermal/phonon engineering by utilization of CNTs and C60.
PMID- 26426676
TI - Sitagliptin increases acute pancreatitis risk within 2 years of its initiation: A
retrospective cohort analysis of the National Health Insurance database in
Taiwan.
AB - PURPOSE: To evaluate the risk of acute pancreatitis hospitalization with
sitagliptin use in patients with type 2 diabetes mellitus (T2DM). METHODS: This
retrospective cohort analysis included newly diagnosed T2DM with onset age >=25
years between 1999 and 2010 from the National Health Insurance database. Ever
users (n = 89,800) and never users (n = 449,000) of sitagliptin were followed
until end of 2011. A time-dependent approach was used to calculate event
incidence and estimate hazard ratios adjusted for propensity score. RESULTS:
During follow-up, 261 ever users and 5,840 never users were hospitalized for
acute pancreatitis (respective incidence, 224.0 and 168.4 per 100,000 person
years), with adjusted hazard ratio of 1.59 (95% CI 1.40-1.81). The respective
hazard ratio for the first, second, and third tertile of time since starting
sitagliptin <9.5, 9.5-21.0, and >21.0 months was 8.10 (6.80-9.65), 1.70 (1.38
2.11), and 0.41 (0.30-0.56); 3.26 (2.67-3.98), 1.86 (1.52-2.27), and 0.76 (0.59
0.98) for cumulative duration <3.7, 3.7-10.3, and >10.3 months; and 3.21 (2.65
3.90), 1.89 (1.54-2.32), and 0.73 (0.57-0.95) for cumulative dose <9,000, 9,000
28,000, and >28,000 mg. CONCLUSIONS: Sitagliptin is associated with a higher risk
of acute pancreatitis within the first 2 years of its initiation. The risk
diminishes thereafter, probably due to the depletion of susceptible patients.
PMID- 26426678
TI - Blue-Black Trachea as a Result of Minocycline-induced Hyperpigmentation.
PMID- 26426677
TI - Neuroimmune pharmacological approaches.
AB - Intestinal inflammation is a major health problem which impairs the quality of
life, impacts mental health and is exacerbated by stress and psychiatric
disturbances which, in turn, can affect disease prognosis and response to
treatment. Accumulating evidence indicates that the immune system is an important
interface between intestinal inflammation and the enteric, sensory, central and
autonomic nervous systems. In addition, the neuroimmune interactions originating
from the gastrointestinal tract are orchestrated by the gut microbiota. This
article reviews some major insights into this complex homeostatic network that
have been achieved during the past two years and attempts to put these advances
into perspective with novel opportunities of pharmacological intervention.
PMID- 26426679
TI - Protecting patients with cardiovascular diseases from catastrophic health
expenditure and impoverishment by health finance reform.
AB - OBJECTIVES: To compare the incidences of catastrophic health expenditure (CHE)
and impoverishment, the risk protection offered by two health financial reforms
and to explore factors associated with CHE and impoverishment among patients with
cardiovascular diseases (CVDs) in rural Inner Mongolia, China. METHODS: Cross
sectional study conducted in 2014 in rural Inner Mongolia, China. Patients with
CVDs aged over 18 years residing in the sample areas for at least one year were
eligible. The definitions of CHE and impoverishment recommended by WHO were
adopted. The protection of CHE and impoverishment was compared between the New
Cooperative Medical Scheme (NCMS) alone and NCMS plus National Essential
Medicines Scheme (NEMS) using the percentage change of incidences for CHE and
impoverishment. Logistic regression was used to explore factors associated with
CHE and impoverishment. RESULTS: The incidences of CHE and impoverishment under
NCMS plus NEMS were 11.26% and 3.30%, respectively, which were lower than those
under NCMS alone. The rates of protection were higher among households with
patients with CVDs covered by NCMS plus NEMS (25.68% and 34.65%, respectively).
NCMS plus NEMS could protect the poor households more from CHE but not
impoverishment. NCMS plus NEMS protected more than one-fourth of households from
CHE and more than one-third from impoverishment. CONCLUSION: NCMS plus NEMS was
more effective at protecting households with patients with CVDs from CHE and
impoverishment than NCMS alone. An integration of NCMS with NEMS should be
expanded. However, further strategies to minimise catastrophic health expenditure
after this health finance reform are still needed.
PMID- 26426680
TI - The Intestinal Microbiome in Bariatric Surgery Patients.
AB - With nearly 39% of the worldwide adult population classified as obese, much of
the globe is facing a serious public health challenge. Increasing rates of
obesity, coupled with the failure of many behavioural and pharmacological
interventions, have contributed to a rise in popularity of bariatric surgery as a
treatment for obesity. Surgery-mediated weight loss was initially thought to be a
direct result of mechanical alterations causing restriction and calorie
malabsorption. However, the mounting evidence suggests that indirect factors
influence the accumulation and storage of fat in patients that have undergone
this procedure. Given the established impact the intestinal microbiota has on
adiposity, it is likely that this complex enteric microbial community contributes
to surgery-mediated weight loss and maintenance of weight loss postsurgery. In
this review, we discuss the physiological and psychological traits exhibited by
bariatric surgery candidates that can be influenced by the intestinal microbiota.
Additionally, we detail the studies that investigated the impact of bariatric
surgery on the intestinal microbiota in humans and mouse models of this
procedure.
PMID- 26426682
TI - Post-transplant lymphoproliferative disorder of the adrenal gland after
allogeneic hematopoietic stem cell transplantation: report of two cases and
literature review.
AB - Post-transplant lymphoproliferative disorder (PTLD) is one of the life
threatening complications after hematopoietic stem cell transplantation (HSCT)
and solid organ transplantation (SOT), and it is associated almost exclusively
with Epstein-Barr virus (EBV). We herein report 2 cases of EBV-associated PTLD
after allogeneic HSCT localized in the adrenal gland. Both patients developed
adrenal tumor within 3 months after HSCT and were successfully treated with
rituximab or tapering immunosuppressive agents. Both remained alive without
recurrence. A literature review revealed 12 reported cases of PTLD involving the
adrenal gland, but the adrenal gland was involved as one of the lesions of
advanced-stage PTLD after SOT. To the best of our knowledge, this is the first
report to show cases of isolated EBV-associated adrenal PTLD after HSCT. PTLD
should be recognized as one of the causes of isolated adrenal tumor after HSCT.
PMID- 26426683
TI - Disinfection of transvaginal ultrasound probes in a clinical setting: comparative
performance of automated and manual reprocessing methods.
AB - OBJECTIVES: Transvaginal and intracavitary ultrasound probes are a possible
source of cross-contamination with microorganisms and thus a risk to patients'
health. Therefore appropriate methods for reprocessing are needed. This study was
designed to compare the standard disinfection method for transvaginal ultrasound
probes in Germany with an automated disinfection method in a clinical setting.
METHODS: This was a prospective randomized controlled clinical study of two
groups. In each group, 120 microbial samples were collected from ultrasound
transducers before and after disinfection with either an automated method
(Trophon EPR(r)) or a manual method (Mikrozid Sensitive(r) wipes). Samples were
then analyzed for microbial growth and isolates were identified to species level.
RESULTS: Automated disinfection had a statistically significantly higher success
rate of 91.4% (106/116) compared with 78.8% (89/113) for manual disinfection (P =
0.009). The risk of contamination was increased by 2.9-fold when disinfection was
performed manually (odds ratio, 2.9 (95% CI, 1.3-6.3)). Before disinfection,
bacterial contamination was observed on 98.8% of probes. Microbial analysis
revealed 36 different species of bacteria, including skin and environmental
bacteria as well as pathogenic bacteria such as Staphylococcus aureus,
enterobacteriaceae and Pseudomonas spp. CONCLUSIONS: Considering the high number
of contaminated probes and bacterial species found, disinfection of the
ultrasound probe's body and handle should be performed after each use to decrease
the risk of cross-contamination. This study favored automated disinfection owing
to its significantly higher efficacy compared with a manual method. Copyright (c)
2015 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 26426681
TI - QseBC, a two-component bacterial adrenergic receptor and global regulator of
virulence in Enterobacteriaceae and Pasteurellaceae.
AB - The QseBC two-component system (TCS) is associated with quorum sensing and
functions as a global regulator of virulence. Based on sequence similarity within
the sensor domain and conservation of an acidic motif essential for signal
recognition, QseBC is primarily distributed in the Enterobacteriaceae and
Pasteurellaceae. In Escherichia coli, QseC responds to autoinducer-3 and/or
epinephrine/norepinephrine. Binding of epinephrine/norepinephrine is inhibited by
adrenergic antagonists; hence QseC functions as a bacterial adrenergic receptor.
Aggregatibacter actinomycetemcomitans QseC is activated by a combination of
epinephrine/norepinephrine and iron, whereas only iron activates the Haemophilus
influenzae sensor. QseC phosphorylates QseB but there is growing evidence that
QseB is activated by non-cognate sensors and regulated by dephosphorylation via
QseC. Interestingly, the QseBC signaling cascades and regulons differ
significantly. In enterohemorrhagic E. coli, QseC induces expression of a second
adrenergic TCS and phosphorylates two non-cognate response regulators, each of
which induces specific sets of virulence genes. This signaling pathway integrates
with other regulatory mechanisms mediated by transcriptional regulators QseA and
QseD and a fucose-sensing TCS and likely controls the level and timing of
virulence gene expression. In contrast, A. actinomycetemcomitans QseC signals
through QseB to regulate genes involved in anaerobic metabolism and energy
production, which may prime cellular metabolism for growth in an anaerobic host
niche. QseC represents a novel target for therapeutic intervention and small
molecule inhibitors already show promise as broad-spectrum antimicrobials.
Further characterization of QseBC signaling may identify additional differences
in QseBC function and inform further development of new therapeutics to control
microbial infections.
PMID- 26426684
TI - Downregulation of the cancer susceptibility protein WRAP53beta in epithelial
ovarian cancer leads to defective DNA repair and poor clinical outcome.
AB - Alterations in the scaffold protein WRAP53beta have previously been linked to
carcinogenesis and, in particular, associated with an increased risk for
epithelial ovarian cancer. Here, we investigated the pathogenic impact and
prognostic significance of WRAP53beta in connection with epithelial ovarian
cancer and examined the underlying mechanisms. We find that reduced expression of
WRAP53beta in ovarian tumors correlated with attenuated DNA damage response and
poor patient survival. Furthermore, in ovarian cancer cell lines, WRAP53beta was
rapidly recruited to DNA double-strand breaks, where it orchestrated the
recruitment of repair factors involved in homologous recombination and non
homologous end joining, including RNF168, 53BP1, BRCA1 and RAD51.
Mechanistically, WRAP53beta accomplishes this by facilitating the necessary
ubiquitinylation at DNA breaks. Finally, we demonstrate that loss of WRAP53beta
significantly impairs the repair of DNA double-strand breaks, resulting in their
accumulation. Our findings establish WRAP53beta as a regulator of homologous
recombination and non-homologous end joining repair in ovarian cancer cells,
suggesting that loss of this protein contributes to the development and/or
progression of ovarian tumors. Moreover, our current observations identify the
nuclear levels of WRAP53beta as a promising biomarker for the survival of
patients with ovarian cancer.
PMID- 26426685
TI - Caspase-8 activation by TRAIL monotherapy predicts responses to IAPi and TRAIL
combination treatment in breast cancer cell lines.
AB - The discovery of cancer cell-selective tumour necrosis factor-related apoptosis
inducing ligand (TRAIL)-induced apoptosis generated broad excitement and
development of TRAIL receptor agonists (TRA) as potential cancer therapy. Studies
demonstrating the synergistic combination effect of SMAC mimetics and TRA further
suggested potentially effective treatment in multiple tumour settings. However,
predictive biomarkers allowing identification of patients that could respond to
treatment are lacking. Here, we described a high throughput combination screen
conducted across a panel of 31 breast cancer cell lines in which we observed
highly synergistic activity between TRAIL and the inhibitors of apoptosis
proteins (IAP) inhibitor (IAPi) AZD5582 in ~30% of cell lines. We detected no
difference in the expression levels of the IAPi or TRAIL-targeted proteins or
common modulators of the apoptotic pathway between the sensitive and resistant
cell lines. Synergistic combination effect of AZD5582 and TRAIL correlated with
sensitivity to TRAIL, but not to AZD5582 as a single agent. TRAIL treatment led
to significantly greater activity of Caspase-8 in sensitive than in resistant
cell lines (P=0.002). The majority (12/14) of AZD5582+TRAIL-resistant cell lines
retained a functional cell death pathway, as they were sensitive to
AZD5582+TNFalpha combination treatment. This suggested that failure of the TRAIL
receptor complex to transduce the death signal to Caspase-8 underlies
AZD5582+TRAIL resistance. We developed a 3D spheroid assay and demonstrated its
suitability for the ex vivo analysis of the Caspase-8 activity as a predictive
biomarker. Altogether, our study demonstrated a link between the functionality of
the TRAIL receptor pathway and the synergistic activity of the IAPi+TRA
combination treatment. It also provided a rationale for development of the
Caspase-8 activity assay as a functional predictive biomarker that could allow
better prediction of the response to IAPi+TRA-based therapies than the analysis
of expression levels of protein biomarkers.
PMID- 26426686
TI - IMP2/p62 induces genomic instability and an aggressive hepatocellular carcinoma
phenotype.
AB - Hepatocellular carcinoma (HCC) represents the third leading cause of cancer
related deaths and commonly develops in inflammatory environments. The IGF2 mRNA
binding protein IMP2-2/IGF2BP2-2/p62 was originally identified as an autoantigen
in HCC. Aim of this study was to investigate a potential pathophysiological role
of p62 in hepatocarcinogenesis. Human HCC tissue showed overexpression of IMP2,
which strongly correlated with the fetal markers AFP and DLK1/Pref-1/FA-1 and was
particularly elevated in tumors with stem-like features and hypervascularization.
Molecular classification of IMP2-overexpressing tumors revealed an aggressive
phenotype. Livers of mice overexpressing the IMP2 splice variant p62 highly
expressed the stem cell marker DLK1 and secreted DLK1 into the blood. p62 was
oncogenic: diethylnitrosamine (DEN)-treated p62 transgenic mice exhibited a
higher tumor incidence and multiplicity than wild types. Tumors of transgenics
showed a more aggressive and stem-like phenotype and displayed more oncogenic
chromosomal aberrations determined with aCGH analysis. DEN-treated p62 transgenic
mice exhibited distinct signs of inflammation, such as inflammatory cytokine
expression and oxidative stress markers, that is, thiobarbituric acid-reactive
substance (TBARS) levels. Reactive oxygen species (ROS) production was elevated
in HepG2 cells, which either overexpressed p62 or were treated with DLK1. p62
induced this ROS production by a DLK1-dependent induction and activation of the
small Rho-GTPase RAC1, activating NADPH oxidase and being overexpressed in human
HCC. Our data indicate that p62/IMP2 promotes hepatocarcinogenesis by an
amplification of inflammation.
PMID- 26426688
TI - Oncogenic potential of hepatitis B virus encoded proteins.
AB - Due to the limited treatment options hepatocellular carcinoma (HCC) is one of the
leading causes of cancer related death, and hepatitis B virus (HBV) infection is
the major risk factor for development of HCC worldwide. HCC is typically preceded
by chronic inflammation, but may also develop in the absence of liver disease on
the basis of HBV infection and even when virus replication is controlled by
antivirals. In this situation, HBV antigen expression persists and direct
oncogenic effects of HBV are integration of the viral DNA into the host genome as
well as direct effects of viral proteins. These factors have to be taken into
account in order to personalize HCC surveillance in CHB and unravel novel
therapeutic approaches.
PMID- 26426687
TI - How do persistent infections with hepatitis C virus cause liver cancer?
AB - Persistent infection with hepatitis C virus (HCV) is associated with an increased
risk of hepatocellular carcinoma (HCC). Cancer typically develops in a setting of
chronic hepatic inflammation and advanced fibrosis or cirrhosis, and such tissue
represents a pre-neoplastic 'cancer field'. However, not all persistent
infections progress to HCC and a combination of viral and host immune factors
likely contributes to carcinogenesis. HCV may disrupt cellular pathways involved
in detecting and responding to DNA damage, potentially adding to the risk of
cancer. Efforts to unravel how HCV promotes HCC are hindered by lack of a robust
small animal model, but a better understanding of molecular mechanisms could
identify novel biomarkers for early detection and allow for development of
improved therapies.
PMID- 26426690
TI - Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional
Characterization of a Novel MCT8 Mutation.
AB - BACKGROUND: Mutations in the thyroid hormone (TH) transporter MCT8 have been
identified as the cause for Allan-Herndon-Dudley Syndrome (AHDS), characterized
by severe psychomotor retardation and altered TH serum levels. Here we report a
novel MCT8 mutation identified in 4 generations of one family, and its functional
characterization. METHODS: Proband and family members were screened for 60 genes
involved in X-linked cognitive impairment and the MCT8 mutation was confirmed.
Functional consequences of MCT8 mutations were studied by analysis of [125I]TH
transport in fibroblasts and transiently transfected JEG3 and COS1 cells, and by
subcellular localization of the transporter. RESULTS: The proband and a male
cousin demonstrated clinical findings characteristic of AHDS. Serum analysis
showed high T3, low rT3, and normal T4 and TSH levels in the proband. A MCT8
mutation (c.869C>T; p.S290F) was identified in the proband, his cousin, and
several female carriers. Functional analysis of the S290F mutant showed decreased
TH transport, metabolism and protein expression in the three cell types, whereas
the S290A mutation had no effect. Interestingly, both uptake and efflux of T3 and
T4 was impaired in fibroblasts of the proband, compared to his healthy brother.
However, no effect of the S290F mutation was observed on TH efflux from COS1 and
JEG3 cells. Immunocytochemistry showed plasma membrane localization of wild-type
MCT8 and the S290A and S290F mutants in JEG3 cells. CONCLUSIONS: We describe a
novel MCT8 mutation (S290F) in 4 generations of a family with Allan-Herndon
Dudley Syndrome. Functional analysis demonstrates loss-of-function of the MCT8
transporter. Furthermore, our results indicate that the function of the S290F
mutant is dependent on cell context. Comparison of the S290F and S290A mutants
indicates that it is not the loss of Ser but its substitution with Phe, which
leads to S290F dysfunction.
PMID- 26426691
TI - Thrombin Generation by Fetoscopic Trauma to the Fetal Membranes: An in vivo and
in vitro Study.
AB - OBJECTIVE: We first aimed to investigate in vivo thrombin generation induced by
fetoscopy, and second we used term membrane explants for measurement of thrombin
generation, thrombin receptor location and induction of selected matrix
metalloproteinases (MMPs) in tissue culture. MATERIALS AND METHODS: In vivo study
(37 cases): samples of amniotic fluid were taken at the beginning and end of
fetoscopy (mean gestational age 26.7 weeks) and analyzed by ELISA for thrombin
antithrombin complexes. In vitro study: fetal membranes were put in culture and
punctured for measurement of thrombin generation by calibrated automated
thrombography and ELISA. Induction of MMP-9 and MMP-2 was analyzed by zymography.
PAR-1 was localized by immunohistochemistry. RESULTS: No significant increase in
thrombin-antithrombin was measured in amniotic fluid obtained during fetoscopy.
In vitro, thrombin generation induced by needle trauma of membrane cultures is
correlated to the amount of plasma. Activity of MMP-9 but not MMP-2 was elevated
in cultured membranes but could not be inhibited by a thrombin inhibitor. On
histology, the thrombin receptor PAR-1 was located in the chorion and decidua,
but not in the amnion. DISCUSSION: Despite the influence of thrombin on punctured
fetal membranes in vitro, the role of thrombin in iatrogenic preterm premature
rupture of membranes is questionable.
PMID- 26426692
TI - Examining the Impact of a Public Health Message on Fish Consumption in Bermuda.
AB - BACKGROUND: In 2003 mean cord blood mercury concentrations in pregnant Bermudian
women exceeded levels associated with adverse health outcomes in children. The
principal mercury source was local fish species. Public health messages were
developed suggesting pregnant women reduce consumption of fish species with
higher mercury concentrations (e.g. swordfish), substituting species containing
lower mercury concentrations, and elevated omega-3 fatty acids (e.g. anchovies).
Recent evidence indicates mercury concentrations in Bermuda's pregnant women have
fallen five- fold. OBJECTIVES: Assess whether changes in women's fish eating
patterns during pregnancy are consistent with the public health messaging.
Determine who is making changes to their diet during pregnancy and why. METHODS:
Mixed methods study with a cross-sectional survey of 121 pregnant women,
including 13 opened-ended interviews. Health system, social vulnerability, public
health messaging, and socio-demographic variables were characterized and related
to changes in fish consumption during pregnancy. Qualitative data were coded
according to nutritional advice messages, comprehension of communication
strategies, and sources of information. RESULTS: 95% of women surveyed
encountered recommendations about fish consumption during pregnancy. 75% reported
modifying fish eating behaviors because of recommendations. Principal sources of
information about fish consumption in pregnancy were health care providers and
the Internet. 71% of women reported reducing consumption of large fish species
with greater mercury levels, but 60% reported reduced consumption of smaller, low
mercury fish. No participant mentioned hearing about the benefits of fish
consumption. More frequent exposure to public health messages during pregnancy
was associated with lower reported consumption. Bermudian born women were less
likely to reduce consumption of large fish species during pregnancy. CONCLUSIONS:
In Bermuda, public health messages advocating reduced consumption of larger,
higher mercury-containing fish species appear effective, but masked the
nutritional value message of small fish species, with low mercury concentration.
Adjustment is needed to better balance the risk communication.
PMID- 26426693
TI - PD98059 Influences Immune Factors and Enhances Opioid Analgesia in Model of
Neuropathy.
AB - Neuropathic pain treatment remains challenging due to ineffective therapy and
resistance to opioid analgesia. Mitogen-activated protein kinase kinase (MAPKK)
have been identified as the crucial regulators of pro- and antinociceptive
factors. We used PD98059, an inhibitor of the MAPKK family members MEK1/2. The
aim of study was to examine the influence of single and/or repeated PD98059 on
nociception and opioid effectiveness in neuropathy. Moreover, we examined how
PD98059 influences selected members of cellular pathways and cytokines. The
PD98059 (2.5 mcg) was intrathecally preemptively administered before chronic
constriction injury (CCI), and then once daily for 7 days. Additionally, at day 7
after CCI the PD98059-treated rats received a single injection of opioids. Using
Western blot and qRT-PCR techniques in PD98059-treated rats we analyzed the mRNA
and/or protein level of p38, ERK1/2, JNK, NF-kappaB, IL-1beta, IL-6, iNOS and IL
10 in the lumbar spinal cord. Our results indicate that PD98059 has an analgesic
effects and potentiates morphine and/or buprenorphine analgesia. Parallel we
observed that PD98059 inhibit upregulation of the CCI-elevated p38, ERK1/2, JNK
and NF-kappaB protein levels. Moreover, PD98059 also prevented increase of pro-
(IL-1beta, IL-6, and iNOS) but enhances anti-nociceptive (IL-10) factors. Summing
up, PD98059 diminished pain and increased the effectiveness of opioids in
neuropathy. The inhibition of MEKs might inactivate a variety of cell signaling
pathways that are implicated in nociception.
PMID- 26426694
TI - Decreased Yes-Associated Protein-1 (YAP1) Expression in Pediatric Hearts with
Ventricular Septal Defects.
AB - BACKGROUND: Ventricular septal defects (VSDs) are the most common and simplest
type of congenital heart diseases (CHDs). Animal studies have suggested that the
downregulation of Yes-associated protein 1 (YAP1) during embryonic development
causes VSD-associated CHDs. However, how YAP1 contributes to isolated VSD (iVSD)
is unclear. METHODS AND RESULTS: Twenty right atrial specimens were obtained from
iVSD patients during routine congenital cardiac surgery and we assessed YAP1
expression in these specimens. For controls, six right atrial specimens were
obtained from normal hearts of children without heart disease, three of whom died
from cerebral palsy, and three who underwent heart transplants. YAP1 mRNA and
protein levels and nuclear localization were significantly reduced in iVSD
specimens compared to normal heart specimens. Concomitantly, mRNA levels of YAP1
downstream targets CTGF and AXL were also significantly decreased in iVSD
specimens. Although Ki67-positive cardiomyocytes in iVSD specimens were
comparable to normal heart specimens, Ki67-positive non-cardiomyocytes were
significantly decreased. CONCLUSIONS: YAP1 expression was markedly decreased in
hearts of iVSD children. Given the important role of YAP1 during heart
development, downregulation of YAP1 expression may contribute to iVSD and affect
the proliferation of non-cardiomyocytes.
PMID- 26426695
TI - The GSTome Reflects the Chemical Environment of White-Rot Fungi.
AB - White-rot fungi possess the unique ability to degrade and mineralize all the
different components of wood. In other respects, wood durability, among other
factors, is due to the presence of extractives that are potential antimicrobial
molecules. To cope with these molecules, wood decay fungi have developed a
complex detoxification network including glutathione transferases (GST). The
interactions between GSTs from two white-rot fungi, Trametes versicolor and
Phanerochaete chrysosporium, and an environmental library of wood extracts have
been studied. The results demonstrate that the specificity of these interactions
is closely related to the chemical composition of the extracts in accordance with
the tree species and their localization inside the wood (sapwood vs heartwood vs
knotwood). These data suggest that the fungal GSTome could reflect the chemical
environment encountered by these fungi during wood degradation and could be a way
to study their adaptation to their way of life.
PMID- 26426697
TI - Zinc-cadmium interactions: Impact on wheat physiology and mineral acquisition.
AB - Increasing concentration of Cd in soil is of great concern due to risk of its
entry into food chain. Zinc (Zn) being antagonist to Cd is an important
micronutrient to ameliorate its toxic effects on plants and to limit its entry
into food chain. A pot experiment was conducted using Cd contaminated soil (30 mg
Cd kg(-1) soil as 3CdSO4 . 8H2O) to investigate the effect of soil and foliar
applied Zn on physiological response and Cd concentration in wheat. In soil, Zn
was applied at 15 and 30 mg Zn kg(-1) soil as zinc sulfate (ZnSO4 . 7H2O). For
foliar applications, 3 and 6 g L(-1) ZnSO4 solution was sprayed on completing
eight weeks of growth. Results indicated that Zn application could effectively
improve physiological performance and mineral content of wheat grown on Cd
contaminated soils. Among different Zn fertilization treatments, foliar
application of 3 g L(-1) ZnSO4 solution recorded the maximum soluble proteins and
the minimum grain-Cd concentration. Soil application of ZnSO4 or foliar
application at 6 g L(-1) did not affect Cd concentration in grains. Zinc
application through both the methods significantly increased phosphorus (P),
potassium (K) and Zn concentrations in shoots. Concentration of P and K in grains
showed positive relationship with that of Zn. In crux, present study suggests
that foliar application of Zn at booting stage in a suitable concentration (3 g
L(-1) ZnSO4 solution) can effectively ameliorate the adverse effects of Cd and
decrease grain-Cd of wheat grown in Cd contaminated soil.
PMID- 26426696
TI - Genetic Variation in miR-146a Is Not Associated with Susceptibility to IgA
Nephropathy in Adults from a Chinese Han Population.
AB - BACKGROUND: MicroRNA 146a (miR-146a) is a 19 to 23 nucleotide long, small non
coding RNA with gene regulatory functions that has influence on the pathogenesis
of many diseases. A single nucleotide polymorphism (rs2910164 C>G) in pre-miR
146a is correlated with the expression of miR-146a. The aim of this study was to
perform an association analysis of rs2910164 with IgA nephropathy in adult
patients from a Chinese Han population. METHODS: A total of 145 patients with
renal biopsy-proved IgA nephropathy (IgAN) and 179 healthy controls were
recruited to the current study. rs2910164 was genotyped by the polymerase chain
reaction (PCR) and high-resolution melting methods (HRM). Clinical
characteristics and pathology grading of patients with IgAN were recorded at the
time of kidney biopsy. RESULT: There were significant differences among the
population of patients grouped by different age of onset in a co-dominant model
(CG vs. CC vs. GG) (p = 0.033) and a recessive model (CG+CC vs. GG) (p = 0.001).
However, no significant difference was observed in the distribution of genotypes
between cases and controls (p = 0.144). There was also no significant difference
between rs2910164 and patient quantitative traits (all p > 0.003) or different
pathology grading (Lee's grading system and tubular atrophy/interstitial fibrosis
in the Oxford classification) (all p > 0.05). CONCLUSIONS: There was no
association of rs2910164 with susceptibility to IgAN in adults from a Chinese Han
population. However, rs2910164 was correlated with the age of onset of IgAN in
adult patients.
PMID- 26426698
TI - Shifting grassland plant community structure drives positive interactive effects
of warming and diversity on aboveground net primary productivity.
AB - Ecosystems worldwide are increasingly impacted by multiple drivers of
environmental change, including climate warming and loss of biodiversity. We
show, using a long-term factorial experiment, that plant diversity loss alters
the effects of warming on productivity. Aboveground primary productivity was
increased by both high plant diversity and warming, and, in concert, warming
(~1.5 degrees C average above and belowground warming over the growing season)
and diversity caused a greater than additive increase in aboveground
productivity. The aboveground warming effects increased over time, particularly
at higher levels of diversity, perhaps because of warming-induced increases in
legume and C4 bunch grass abundances, and facilitative feedbacks of these species
on productivity. Moreover, higher plant diversity was associated with the
amelioration of warming-induced environmental conditions. This led to cooler
temperatures, decreased vapor pressure deficit, and increased surface soil
moisture in higher diversity communities. Root biomass (0-30 cm) was likewise
consistently greater at higher plant diversity and was greater with warming in
monocultures and at intermediate diversity, but at high diversity warming had no
detectable effect. This may be because warming increased the abundance of
legumes, which have lower root : shoot ratios than the other types of plants. In
addition, legumes increase soil nitrogen (N) supply, which could make N less
limiting to other species and potentially decrease their investment in roots. The
negative warming * diversity interaction on root mass led to an overall negative
interactive effect of these two global change factors on the sum of above and
belowground biomass, and thus likely on total plant carbon stores. In total,
plant diversity increased the effect of warming on aboveground net productivity
and moderated the effect on root mass. These divergent effects suggest that
warming and changes in plant diversity are likely to have both interactive and
divergent impacts on various aspects of ecosystem functioning.
PMID- 26426699
TI - Host-Guest Interaction-Mediated Construction of Hydrogels and Nanovesicles for
Drug Delivery.
AB - Hand-in-hand or head-to-head: A novel naphthalimide derivative is successfully
designed and synthesized, which can self-assemble to produce hydrogels. When
injecting this compound into CB[8] solution, the nanovesicles are obtained with a
narrow size distribution. The cytotoxicity assay confirms that doxorubicin-loaded
nanocarriers show therapeutic effects to cancer cells.
PMID- 26426700
TI - Association between left ventricular mass, androgens, adiposity and insulin
resistance in girls with precocious pubarche: a case-control study.
AB - OBJECTIVE: Precocious pubarche (PP) has been linked to higher prevalence of
metabolic disturbances and polycystic ovary syndrome (PCOS). The aim of the study
was to assess echocardiographic parameters in PP girls and to analyse their
relationship with androgens and insulin resistance (IR). DESIGN: Case-control
study. PATIENTS: Thirty-five PP girls and 35 healthy age-matched controls.
MEASUREMENTS: Clinical, hormonal and metabolic profiles, echocardiography, body
composition and oral glucose tolerance test. RESULTS: Chronological age (10.04 +/
2.6 years in PP vs 10.13 +/- 2.56 years in controls, P = 0.227), and pubertal
stage at the time of the study were similar between the groups. PP girls had
higher free androgen index (FAI) [1.39 (0.48-3.64) vs 1.06 (0.39-1.7), P = 0.005]
and QUICKI (0.58 +/- 0.08 vs 0.63 +/- 0.12, P = 0.021). However, HOMA-IR was not
significantly different between the groups [2.79 (1.84-4.05) vs 2.15 (1.09-3.23),
P = 0.085]. After adjusting for total body fat, left ventricular mass (LVM) was
higher in the PP group (97.31 +/- 33.37 vs 81.25 +/- 19.06 g, P = 0.017) as well
as A' wave (5.66 +/- 1.34 vs 5.09 +/- 0.98 cm/s, P = 0.025), a measurement of
diastolic function. FAI and total body fat were independent predictors of higher
LVM and together with HOMA-IR contributed 72% of LVM variability in the PP group.
CONCLUSION: In this study with PP girls, greater LVM, associated with higher
androgen levels, IR and total body fat, occurred early in pubertal development.
PMID- 26426701
TI - Bayes Node Energy Polynomial Distribution to Improve Routing in Wireless Sensor
Network.
AB - Wireless Sensor Network monitor and control the physical world via large number
of small, low-priced sensor nodes. Existing method on Wireless Sensor Network
(WSN) presented sensed data communication through continuous data collection
resulting in higher delay and energy consumption. To conquer the routing issue
and reduce energy drain rate, Bayes Node Energy and Polynomial Distribution
(BNEPD) technique is introduced with energy aware routing in the wireless sensor
network. The Bayes Node Energy Distribution initially distributes the sensor
nodes that detect an object of similar event (i.e., temperature, pressure, flow)
into specific regions with the application of Bayes rule. The object detection of
similar events is accomplished based on the bayes probabilities and is sent to
the sink node resulting in minimizing the energy consumption. Next, the
Polynomial Regression Function is applied to the target object of similar events
considered for different sensors are combined. They are based on the minimum and
maximum value of object events and are transferred to the sink node. Finally, the
Poly Distribute algorithm effectively distributes the sensor nodes. The energy
efficient routing path for each sensor nodes are created by data aggregation at
the sink based on polynomial regression function which reduces the energy drain
rate with minimum communication overhead. Experimental performance is evaluated
using Dodgers Loop Sensor Data Set from UCI repository. Simulation results show
that the proposed distribution algorithm significantly reduce the node energy
drain rate and ensure fairness among different users reducing the communication
overhead.
PMID- 26426702
TI - Amniotic fluid biochemistry in isolated polyhydramnios: a series of 464 cases.
AB - OBJECTIVE: To report amniotic fluid biochemistry in a large series of 464 cases
of isolated polyhydramnios in order to analyze both the outcome and the benefit
of amniotic fluid biochemistry. METHODS: This retrospective cohort (2008-2012)
included polyhydramnios cases for which amniotic fluid samples were sent to our
laboratory for biochemical analysis (total protein, alpha-fetoprotein and gamma
glutamyl transpeptidase) so as to investigate the etiology. A Bartter index and
an esophageal atresia index were defined. Final diagnoses were compared between
groups to determine the association between these indices and the frequency and
type of adverse outcomes. RESULTS: Among 464 cases of polyhydramnios considered
isolated at ultrasound examination, severe fetal diseases were diagnosed in 136
(29.3%): 46 (9.9%) chromosomal anomalies, 28 (6%) Bartter syndrome, 23 (4.95%)
other genetic syndromes, 22 (4.75%) swallowing disorders and 17 (3.7%) uro
nephrological disorders. Amniotic fluid biochemistry identified esophageal
atresia with 66.6% (10/15) sensitivity and 100% specificity and Bartter syndrome
with 85.7% (24/28) sensitivity and 84.2% specificity. CONCLUSION: Isolated
polyhydramnios is associated with a high risk of severe fetal diseases. Molecular
cytogenetics and amniotic fluid biochemistry are helpful tools.
PMID- 26426703
TI - Biocompatibility and biomechanical analysis of elastic TPU threads as new suture
material.
AB - High suture tension is one of the causes for many wound-healing problems.
Constriction of tissue within the suture loops of nonelastic sutures can lead to
cutting of the suture through tissues and necrosis of the tissue within these
loops. The use of elastic materials in new suture types could give the material
the ability to adapt tension to the tissue requirements and subsequently lead to
more vital tissue within its loops. We evaluated the foreign body host response,
as indicator of biocompatibility, to a new thermoplastic poly(carbonate) urethane
(TPU) synthetic suture material in a rat model compared with standard nonelastic
polypropylene (PP) sutures. Tissue samples were collected at 7 and 21 days, and
host response was evaluated. Subsequently, suture tension curves of the new
elastic sutures for the first 30 min after knotting were recorded in a pig model.
The new TPU sutures showed an improved foreign body response when compared with
that of PP, with a reduction in the amount of macrophages surrounding the
material. Tension experiments showed a superior tension curve for TPU sutures,
with a major reduction in peak suture tension when compared with that of standard
PP sutures, while still retaining adequate tension after 30 min. (c) 2015 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 99-106, 2017.
PMID- 26426705
TI - Quantitative Contact Resonance Force Microscopy for Viscoelastic Measurement of
Soft Materials at the Solid-Liquid Interface.
AB - Viscoelastic property measurements made at the solid-liquid interface are key to
characterizing materials for a variety of biological and industrial applications.
Further, nanostructured materials require nanoscale measurements. Here, material
loss tangents (tan delta) were extracted from confounding liquid effects in
nanoscale contact resonance force microscopy (CR-FM), an atomic force microscope
based technique for observing mechanical properties of surfaces. Obtaining
reliable CR-FM viscoelastic measurements in liquid is complicated by two effects.
First, in liquid, spurious signals arise during cantilever excitation. Second, it
is challenging to separate changes to cantilever behavior due to the sample from
changes due to environmental damping and added mass effects. We overcame these
challenges by applying photothermal cantilever excitation in multiple resonance
modes and a predictive model for the hydrodynamic effects. We demonstrated
quantitative, nanoscale viscoelastic CR-FM measurements of polymers at the solid
liquid interface. The technique is demonstrated on a point-by-point basis on
polymer samples and while imaging in contact mode on a fixed plant cell wall.
Values of tan delta for measurements made in water agreed with the values for
measurements in air for some experimental conditions on polystyrene and for all
examined conditions on polypropylene.
PMID- 26426706
TI - Exploring water as building bricks in enzyme engineering.
AB - A novel enzyme engineering strategy for accelerated catalysis based on
redesigning a water network through protein backbone deshielding is presented.
Fundamental insight into the energetic consequences associated with the design is
discussed in the light of experimental results and computer simulations. Using
water as biobricks provides unique opportunities when transition state
stabilisation is not easily attained by traditional enzyme engineering.
PMID- 26426704
TI - Cohort Study of the Success of Controlled Weight Loss Programs for Obese Dogs.
AB - BACKGROUND: Most weight loss studies in obese dogs assess rate and percentage of
weight loss in the first 2-3 months, rather than the likelihood of successfully
reaching target weight. OBJECTIVE: To determine outcome of controlled weight loss
programs for obese dogs, and to determine the factors associated with successful
completion. ANIMALS: 143 obese dogs undergoing a controlled weight loss program.
METHODS: This was a cohort study of obese dogs attending a referral weight
management clinic. Dogs were studied during their period of weight loss, and
cases classified according to outcome as "completed" (reached target weight),
"euthanized" (was euthanized before reaching target weight), or "stopped
prematurely" (program stopped early for other reasons). Factors associated with
successful completion were assessed using simple and multiple logistic
regression. RESULTS: 87/143 dogs (61%) completed their weight loss program, 11
[8%] died or were euthanized, and the remaining 45 [32%] stopped prematurely.
Reasons for dogs stopping prematurely included inability to contact owner,
refusal to comply with weight management advice, or development of another
illness. Successful weight loss was positively associated with a faster rate (P <
.001), a longer duration (P < .001), and feeding a dried weight management diet
(P = .010), but negatively associated with starting body fat (P < .001), and use
of dirlotapide (P = .0046). CONCLUSIONS AND CLINICAL RELEVANCE: Just over half of
all obese dogs on a controlled weight loss program reach their target weight.
Future studies should better clarify reasons for success in individual cases, and
also the role of factors such as activity and behavioral modification.
PMID- 26426707
TI - Education and Imaging. Hepatobiliary and Pancreatic: Role of CT angiography in
the evaluation of liver involvement in Rendu-Osler-Weber syndrome.
PMID- 26426708
TI - Ultrafast Photoinduced Charge Separation Leading to High-Energy Radical Ion-Pairs
in Directly Linked Corrole-C60 and Triphenylamine-Corrole-C60 Donor-Acceptor
Conjugates.
AB - Closely positioned donor-acceptor pairs facilitate electron- and energy-transfer
events, relevant to light energy conversion. Here, a triad system TPACor-C60 ,
possessing a free-base corrole as central unit that linked the energy donor
triphenylamine (TPA) at the meso position and an electron acceptor fullerene
(C60) at the beta-pyrrole position was newly synthesized, as were the component
dyads TPA-Cor and Cor-C60. Spectroscopic, electrochemical, and DFT studies
confirmed the molecular integrity and existence of a moderate level of
intramolecular interactions between the components. Steady-state fluorescence
studies showed efficient energy transfer from (1) TPA* to the corrole and
subsequent electron transfer from (1) corrole* to fullerene. Further studies
involving femtosecond and nanosecond laser flash photolysis confirmed electron
transfer to be the quenching mechanism of corrole emission, in which the electron
transfer products, the corrole radical cation (Cor(?+) in Cor-C60 and TPA-Cor(?+)
in TPACor-C60) and fullerene radical anion (C60(?-)), could be spectrally
characterized. Owing to the close proximity of the donor and acceptor entities in
the dyad and triad, the rate of charge separation, kCS , was found to be about
10(11) s(-1), suggesting the occurrence of an ultrafast charge-separation
process. Interestingly, although an order of magnitude slower than kCS , the rate
of charge recombination, kCR , was also found to be rapid (kCR ~10(10) s(-1)),
and both processes followed the solvent polarity trend
DMF>benzonitrile>THF>toluene. The charge-separated species relaxed directly to
the ground state in polar solvents while in toluene, formation of (3) corrole*
was observed, thus implying that the energy of the charge-separated state in a
nonpolar solvent is higher than the energy of (3) corrole* being about 1.52 eV.
That is, ultrafast formation of a high-energy charge-separated state in toluene
has been achieved in these closely spaced corrole-fullerene donor-acceptor
conjugates.
PMID- 26426709
TI - The Effect of Smoking on Spinal Cord Healing Following Surgical Treatment of
Cervical Myelopathy.
AB - STUDY DESIGN: Retrospective cohort. OBJECTIVE: The purpose of this study was to
compare outcomes of surgical treatment of cervical myelopathy between smokers and
nonsmokers as assessed by the Nurick score. SUMMARY OF BACKGROUND DATA: The
harmful effects of smoking on healing have been well established. However, the
effect of smoking on postoperative outcomes for cervical myelopathy has not been
specifically evaluated. METHODS: The medical records of 212 patients who
underwent surgery for cervical spondylotic myelopathy were reviewed. Inclusion
criteria were the diagnosis of cervical spondylotic myelopathy with a Nurick
score, surgical intervention, and at least 2 years of follow-up. The patients
were categorized into 2 groups according to smoking status and stratified
according to pack years and packs per day. Age at presentation, sex, preoperative
and postoperative Nurick score, duration of symptoms preoperatively, duration of
follow-up, procedure performed, surgical approach, number of levels fused,
diabetes status, cocaine use, ethanol use, preoperative magnetic resonance
imaging signal change, and whether the patient belonged to the Veterans
Administration (VA) were recorded. Analysis was done using simple linear
regression and multiple regression. RESULTS: Univariate analysis demonstrated a
postoperative improvement in nonsmokers of 1.53 points on the Nurick scale
compared with 0.6 points in smokers (P < 0.001). There is a progressive decrease
in improvement as the number of pack years and packs per day increase (P <
0.001). There is a greater improvement in Nurick score with greater (worse)
preoperative score but only in patients with fewer than 25 pack years. Smoking
status is not associated with preoperative Nurick score. CONCLUSION: Smoking
status is associated with poor improvement in Nurick score after surgical
treatment of cervical myelopathy. Smoking may have a directly toxic effect on the
intrinsic healing capability of the spinal cord, particularly beyond 25 pack
years. LEVEL OF EVIDENCE: 3.
PMID- 26426710
TI - Safety and Efficacy of Reconstruction of Complex Cervical Spine Pathology Using
Pedicle Screws Inserted with Stealth Navigation and 3D Image-Guided (O-Arm)
Technology.
AB - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To determine safety and efficacy
of cervical pedicle screw placement using O-Arm and Stealth Navigation in
patients with cervicothoracic spinal deformities and revision subaxial cervical
pathology. SUMMARY OF BACKGROUND DATA: Cervical pedicle screws are
biomechanically advantageous to other posterior cervical fixation techniques;
however, their use is limited by concerns for neurovascular injury. Few clinical
reports exist on their placement safety and efficacy using modern navigation
systems. METHODS: Adults who had cervical pedicle screws inserted using O-Arm and
Stealth Navigation between November 2007 and January 2014 and with a minimum 1
year follow-up were retrospectively studied. Screw insertion safety, surgical
complications, need for reoperation, and clinical outcomes [Neck Disability
Index, EQ-5D, numeric pain rating scales] were evaluated. RESULTS: 21 patients
(female-10; male-11; average age 63 yr [32-83 yr]) met inclusion criteria.
Average follow-up was 29.8 months (12-81.6 mo). Reconstruction of C2 and the
subaxial cervical spine included 8 primary operations for cervicothoracic
kyphosis and 13 revision operations. 121 pedicle screws were placed (C2: 4, C3:
20, C4: 22, C5: 23, C6: 18, C7: 34) using Stealth Navigation. The average number
of screws placed per case was 6 (1-12). Greater than 99% of screws were placed
safely without neurovascular injury. 1 screw (0.8%) was noted postoperatively to
critically breach the medial wall and was associated with an acute C5 nerve root
palsy. 2 patients required revisions for postoperative iatrogenic foraminal
stenosis and associated C8 radiculopathies. No vascular complications due to
aberrant screw placement occurred. There were significant improvements (P < 0.05)
in EQ-5D utility scores and neck and arm pain. Neck Disability Index scores
decreased on average by 10 points (P = 0.12). CONCLUSION: Placement of cervical
pedicle screws using O-Arm/Stealth Navigation in this series was a safe and
effective method for posterior stabilization in cervicothoracic deformity and
revision operations of the subaxial cervical spine. LEVEL OF EVIDENCE: 4.
PMID- 26426711
TI - American Spinal Injury Association Impairment Scale Predicts the Need for
Tracheostomy After Cervical Spinal Cord Injury.
AB - STUDY DESIGN: Retrospective review. OBJECTIVE: The objective of this study was to
evaluate the ability of the American Spinal Injury Association (ASIA) Impairment
Scale and neurological level of injury to predict the need for mechanical
ventilation as well as tracheostomy. SUMMARY OF BACKGROUND DATA: High-level
cervical spinal cord injuries, high Injury Severity Score, and low Glasgow Coma
Scale have been shown to predict tracheostomy. METHODS: A total of 383 patients
with fractures, dislocations, or ligamentous injury of the cervical spine were
included in the study. Charts were reviewed to determine demographics, Injury
Severity Score, Glasgow Coma Scale, presence and severity of chest injuries,
length of hospital stay, intensive care unit stay, mechanical ventilation time,
and mortality. RESULTS: Fifty-nine patients (15.4%) underwent tracheostomy. An
ASIA Impairment Scale of A had a specificity of 98.8% and sensitivity of 32.2%
for predicting the need for tracheostomy. This yielded a 1.2% false-positive
rate. The ASIA Impairment Scale remained the most significant predictor after
regression for Injury Severity Score, Glasgow Coma Scale, and Chest Abbreviated
Injury Scale. Neurological level of injury was not a significant predictor of
tracheostomy. CONCLUSION: An ASIA Impairment Scale of A at any level of injury is
a specific predictor of the need for tracheostomy with a low false-positive rate.
Given the relatively low risk of early tracheostomy and the potential benefits,
an ASIA Impairment Scale of A would be a sensible early criterion to determine
the need for tracheostomy. LEVEL OF EVIDENCE: 3.
PMID- 26426712
TI - Radiographical and Implant-Related Complications in Adult Spinal Deformity
Surgery: Incidence, Patient Risk Factors, and Impact on Health-Related Quality of
Life.
AB - STUDY DESIGN: A multicenter, prospective review of surgical patients with adult
spine deformity. OBJECTIVE: Assessment of the incidence, risk factor, and impact
of radiographical and implant-related complications (RIC) on health-related
quality of life measures. SUMMARY OF BACKGROUND DATA: This study provides
assessment of the incidence of RIC in adult spinal deformity surgery and impact
of these complications on need for reoperation. Risk factors for development of
RIC are also assessed, as well as the impact of these complications on health
related quality of life (HRQOL) outcomes measures. METHODS: A multicenter,
prospective database of surgical patients with adult spinal deformity was
reviewed. All patients with complete 2-year follow-up were included. HRQOL was
measured using the Oswestry Disability Index, General Health Survey (36-Item
Short Form Health Survey [SF-36]), and Scoliosis Research Society-22 (SRS-22r) at
baseline, 6 weeks, 1 year, and 2 years postoperatively. Univariate testing was
performed as appropriate. Multivariate logistic regression modeling was used to
determine independent predictors of RIC. Multivariate repeated-measures mixed
models were used to examine HRQOL, accounting for confounders. RESULTS: A total
of 245 patients met inclusion criteria. The incidence of RIC was 31.7% and 52.6%
of those patients required reoperation. Rod breakage accounted for 47% of the
implant-related complications, and proximal junctional kyphosis accounted for
54.5% of radiographical complications. Univariate analysis identified the
following potential risk factors for RIC: weight, American Society of
Anesthesiologists score, revision, stopping the fusion in the lower thoracic
spine, worse SRS-Schwab classification modifiers (pelvic tilt++, pelvic incidence
minus lumbar lordosis++, sagittal vertical axis++), higher T1 spinopelvic
inclination, and higher T1 slope. Independent predictors of RIC as identified on
multivariate logistic regression included American Society of Anesthesiologists
(odds ratio: 1.75, P = 0.029) and sagittal vertical axis modifier ++ (odds ratio
3.43, P = 0.0001). The RIC and no RIC groups each experienced significant
improvement over time, as measured on the Oswestry Disability Index (P = 0.0001),
SF-36 (P = 0.0001), and SRS-22r (P = 0.0001). However, the rate of improvement
over time was less for patients with RIC (SRS-22r P = 0.043, SF-36 P = 0.0001).
CONCLUSION: This study identified that nearly one-third of patients undergoing
adult spinal deformity surgery experienced a radiographical or implant-related
complication, and that just more than one-half of these patients experiencing
complication required a reoperation within 2 years of surgery. These
complications significantly affected HRQOL measures. Baseline patient
characteristics and parameters of the SRS-Schwab classification can be used to
help identify those patients at greater risk. LEVEL OF EVIDENCE: 3.
PMID- 26426713
TI - The Incidence of Durotomy and its Clinical and Economic Impact in Primary, Short
segment Lumbar Fusion: An Analysis of 17,232 Cases.
AB - STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To determine the
incidence of durotomy in primary short-segment lumbar fusion and assess its
clinical and economic impacts. SUMMARY OF BACKGROUND DATA: The incidence of
durotomy during primary lumbar fusion and its economic impact are not well
described. METHODS: The Nationwide Inpatient Sample was queried for all primary 1
or 2-level lumbar fusions performed in adults for lumbar spinal stenosis between
2009 and 2011; only elective cases without concurrent diagnoses of vertebral
infection, fracture, or tumor were included. chi and t-tests were used as
appropriate to compare categorical and continuous variables, respectively.
Multivariate regression analysis was performed to identify factors independently
associated with incidental durotomy, as well as total hospital charges, costs,
and length of stay. RESULTS: Among 17,232 cases, 802 incidental durotomies were
identified (rate 4.65%). The multivariate odds of durotomy in the oldest patients
(age >= 73) were 2.4 times greater than the odds of durotomy in the youngest
patients (age <= 56; P < 0.0001). Durotomy was associated with increased
neurological complications and longer hospital stay. Length of stay was a
significant driver of cost. The multivariate odds of dural tears in teaching
hospitals was significantly higher compared with nonteaching hospitals (odds
ratio 1.27; 95% confidence interval, 1.06-1.52; P < 0.005). Durotomy was
associated with a $10,885 increase in total hospital charges, and a $3,873
increase in estimated total costs (compared with no durotomy group with P <
0.0001). CONCLUSION: Increasing age is a risk factor for durotomy in primary
lumbar fusion. Durotomy is associated with neurological complications, increased
length of stay, greater healthcare costs, and is more common in teaching
hospitals. Length of stay is an independent driver of cost and complications.
LEVEL OF EVIDENCE: 3.
PMID- 26426714
TI - Dante and Musculoskeletal Diseases: Anatomy and Pathophysiology of Orthopedic and
Spinal Disorders in the Middle Ages.
PMID- 26426715
TI - The Reliability and Validity of the Thoracolumbar Injury Classification System in
Pediatric Spine Trauma.
AB - STUDY DESIGN: The thoracolumbar injury classification system (TLICS) was
evaluated in 20 consecutive pediatric spine trauma cases. OBJECTIVE: The purpose
of this study was to determine the reliability and validity of the TLICS in
pediatric spine trauma. SUMMARY OF BACKGROUND DATA: The TLICS was developed to
improve the categorization and management of thoracolumbar trauma. TLICS has been
shown to have good reliability and validity in the adult population. METHODS: The
clinical and radiographical findings of 20 pediatric thoracolumbar fractures were
prospectively presented to 20 surgeons with disparate levels of training and
experience with spinal trauma. These injuries were consecutively scored using the
TLICS. Cohen unweighted kappa coefficients and Spearman rank order correlation
values were calculated for the key parameters (injury morphology, status of
posterior ligamentous complex, neurological status, TLICS total score, and
proposed management) to assess the inter-rater reliabilities. Five surgeons
scored the same cases 3 months later to assess the intra-rater reliability. The
actual management of each case was then compared with the treatment recommended
by the TLICS algorithm to assess validity. RESULTS: The inter-rater kappa
statistics of all subgroups (injury morphology, status of the posterior
ligamentous complex, neurological status, TLICS total score, and proposed
treatment) were within the range of moderate to substantial reproducibility
(0.524-0.958). All subgroups had excellent intra-rater reliability (0.748-1.000).
The various indices for validity were calculated (80.3% correct, 0.836
sensitivity, 0.785 specificity, 0.676 positive predictive value, 0.899 negative
predictive value). Overall, TLICS demonstrated good validity. CONCLUSION: The
TLICS has good reliability and validity when used in the pediatric population.
The inter-rater reliability of predicting management and indices for validity are
lower than those in adults with thoracolumbar fractures, which is likely due to
differences in the way children are treated for certain types of injuries. TLICS
can be used to reliably categorize thoracolumbar injuries in the pediatric
population; however, modifications may be needed to better guide treatment in
this specific patient population. LEVEL OF EVIDENCE: 4.
PMID- 26426717
TI - Conjunctival Melanoma-Clinical Pearls Now, Hope for the Future.
PMID- 26426718
TI - A Narrow QRS Tachycardia with Unusual Electrophysiological Characteristics: What
Is the Mechanism?
PMID- 26426723
TI - Microscopic Mechanism of Doping-Induced Kinetically Constrained Crystallization
in Phase-Change Materials.
AB - A comprehensive microscopic mechanism of doping-induced kinetically constrained
crystallization in phase-change materials is provided by investigating structural
and dynamical dopant characteristics via ab initio molecular dynamics
simulations. The information gained from this study may provide a basis for a
fast screening of dopant species for electronic memory devices, or for
understanding the general physics involved in the crystallization of doped
glasses.
PMID- 26426719
TI - Engineering a Constrained Peptidic Scaffold towards Potent and Selective Furin
Inhibitors.
AB - We report the engineering of the monocyclic sunflower trypsin inhibitor (SFTI
1[1,14]) into a potent furin inhibitor. In a rational approach, we converted the
native scaffold of this trypsin-like serine protease inhibitor into a subtilisin
like one by substitutions in the canonical and, particularly, in the substrate
binding loop. Although the substrate sequence for furin is Arg-X-Arg/Lys-Arg?,
the most potent inhibitor had a lysine at position P1. C-terminally truncated
versions demonstrated the strongest activity, thus suggesting a lack of
interaction between this motif and the surface of furin. This observation was
further supported by molecular modeling. With an inhibition constant of 0.49 nm,
the engineered peptide H-KRCKKSIPPICF-NH2 is a promising compound for further
development of furin inhibitors aimed at controlling the activity of this
protease in vitro and in vivo.
PMID- 26426729
TI - Atmospheric Deposition of Indium in the Northeastern United States: Flux and
Historical Trends.
AB - The metal indium is an example of an increasingly important material used in
electronics and new energy technologies, whose environmental behavior and
toxicity are poorly understood despite increasing evidence of detrimental health
impacts and human-induced releases to the environment. In the present work, the
history of indium deposition from the atmosphere is reconstructed from its
depositional record in an ombrotrophic bog in Massachusetts. A novel freeze
coring technique is used to overcome coring difficulties posed by woody roots and
peat compressibility, enabling retrieval of relatively undisturbed peat cores
dating back more than a century. Results indicate that long-range atmospheric
transport is a significant pathway for the transport of indium, with peak
concentrations of 69 ppb and peak fluxes of 1.9 ng/cm2/yr. Atmospheric deposition
to the bog began increasing in the late 1800s/early 1900s, and peaked in the
early 1970s. A comparison of deposition data with industrial production and
emissions estimates suggests that both coal combustion and the smelting of lead,
zinc, copper, and tin sulfides are sources of indium to the atmosphere in this
region. Deposition appears to have decreased considerably since the 1970s,
potentially a visible effect of particulate emissions controls instated in North
America during that decade.
PMID- 26426725
TI - Freestanding Artificial Synapses Based on Laterally Proton-Coupled Transistors on
Chitosan Membranes.
AB - Freestanding synaptic transistors are fabricated on solution-processed chitosan
membranes. A short-term memory to long-term memory transition is observed due to
proton-related electrochemical doping under repeated pulse stimulus. Moreover,
freestanding artificial synaptic devices with multiple presynaptic inputs are
investigated, and spiking logic operation and logic modulation are realized.
PMID- 26426730
TI - Effect of friction on the peeling test at zero-degrees.
AB - We describe the peeling of an elastomeric strip adhering to a glass plate through
van der Waals interactions in the limit of a zero peeling angle. In contrast to
classical studies that predict a saturation of the pulling force, in this lap
test configuration the force continuously increases, while a sliding front
propagates along the tape. The strip eventually detaches from the substrate when
the front reaches its end. Although the evolution of the force is reminiscent of
recent studies involving a compliant adhesive coupled with a rigid backing, the
progression of a front is in contradiction with such a mechanism. To interpret
this behavior, we estimate the local shear stress at the interface by monitoring
the deformation of the strip. Our results are consistent with a nearly constant
friction stress in the sliding zone in agreement with other experimental
observations where adhesion and friction are observed.
PMID- 26426732
TI - Correction to "Simple, Chemoselective, Catalytic Olefin Isomerization".
PMID- 26426731
TI - Sequence and structure-based prediction of fructosyltransferase activity for
functional subclassification of fungal GH32 enzymes.
AB - Sucrolytic enzymes catalyse sucrose hydrolysis or the synthesis of
fructooligosaccharides (FOSs), a prebiotic in human and animal nutrition. FOS
synthesis capacity differs between sucrolytic enzymes. Amino-acid-sequence-based
classification of FOS synthesizing enzymes would greatly facilitate the in silico
identification of novel catalysts, as large amounts of sequence data lie
untapped. The development of a bioinformatics tool to rapidly distinguish between
high-level FOSs synthesizing predominantly sucrose hydrolysing enzymes from
fungal genomic data is presented. Sequence comparison of functionally
characterized enzymes displaying low- and high-level FOS synthesis revealed
conserved motifs unique to each group. New light is shed on the sequence context
of active site residues in three previously identified conserved motifs. We
characterized two enzymes predicted to possess low- and high-level FOS synthesis
activities based on their conserved motif sequences. FOS data for the enzymes
confirmed our successful prediction of their FOS synthesis capacity. Structural
comparison of enzymes displaying low- and high-level FOS synthesis identified
steric hindrance between nystose and a long loop region present only in low-level
FOS synthesizers. This loop is proposed to limit the synthesis of FOS species
with higher degrees of polymerization, a phenomenon observed among enzymes
displaying low-level FOS synthesis. Conserved sequence motifs surrounding
catalytic residues and a distant structural determinant were identifiers of FOS
synthesis capacity and allow for functional annotation of sucrolytic enzymes
directly from amino acid sequence. The tool presented may also be useful to study
the structure-function relationships of beta-fructofuranosidases by identifying
mutations present in a group of closely related enzymes displaying similar
function.
PMID- 26426733
TI - Light emitting diodes based on carbon dots derived from food, beverage, and
combustion wastes.
AB - One important resource for material synthesis is waste. Utilization of waste as a
resource for material synthesis is an environmentally responsible approach that
reduces the need for virgin resources and subsequent processing. In this report a
method to produce multicolored, luminescent carbon dots (CDs) and subsequent
fabrication of light emitting diodes from food, beverage, and combustion wastes,
is discussed. Apart from food and beverages, combustion exhaust was also utilized
for CDs production. Optical characterization results suggest that CDs from waste
food and beverages are more luminescent than those produced from combustion
waste.
PMID- 26426734
TI - Diversity Oriented Synthesis of Polycyclic Heterocycles through the Condensation
of 2-Amino[1,2,4]triazolo[1,5-a]pyrimidines with 1,3-Diketones.
AB - The acid-catalyzed condensation between 2-aminosubstituted [1,2,4]triazolo[1,5
a]pyrimidines and their analogues with various saturation of the pyrimidine ring
and 1,3-diketones or 1,1,3,3-tetramethoxypropane was evaluated as a new approach
for the synthesis of diversely substituted polycyclic derivatives of
triazolopyrimidine. The reaction of 4,5,6,7-tetrahydro- or aromatic
aminotriazolopyrimidines results in selective formation of the corresponding
[1,2,4]triazolo[1,5-a:4,3-a']dipyrimidin-5-ium salts, and the condensation of
substrates containing the 4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine fragment
is accompanied by a cascade rearrangement with unusual recyclization of the
dihydropyrimidine ring to yield partially hydrogenated [1,2,4]triazolo[1,5-a:4,3
a']dipyrimidin-5-ium or pyrimido[1',2':1,5][1,2,4]triazolo[3,4-b]quinazolin-5-ium
salts. The proposed methodology exhibits a wide scope, providing rapid access to
polycondensed derivatives of the [1,2,4]triazolo[1,5-a]pyrimidine scaffold. DFT
calculations of the Gibbs free energies of possible isomers were performed to
rationalize the experimentally observed reactivity and selectivity.
PMID- 26426735
TI - Incidences of Unfavorable Events in the Management of Low-Risk Papillary
Microcarcinoma of the Thyroid by Active Surveillance Versus Immediate Surgery.
AB - BACKGROUND: The incidence of papillary microcarcinoma (PMC) of the thyroid is
rapidly increasing globally, making the management of PMC an important clinical
issue. Excellent oncological outcomes of active surveillance for low-risk PMC
have been reported previously. Here, unfavorable events following active
surveillance and surgical treatment for PMC were studied. METHODS: From February
2005 to August 2013, 2153 patients were diagnosed with low-risk PMC. Of these,
1179 patients chose active surveillance and 974 patients chose immediate surgery.
The oncological outcomes and the incidences of unfavorable events of these groups
were analyzed. RESULTS: In the active surveillance group, 94 patients underwent
surgery for various reasons; tumor enlargement and the appearance of novel lymph
node metastases were the reasons in 27 (2.3%) and six patients (0.5%),
respectively. One of the patients with conversion to surgery had nodal
recurrence, and five patients in the immediate surgery group had a recurrence in
a cervical node or unresected thyroid lobe. All of these recurrences were
successfully treated. None of the patients had distant metastases, and none died
of the disease. The immediate surgery group had significantly higher incidences
of transient vocal cord paralysis (VCP), transient hypoparathyroidism, and
permanent hypoparathyroidism than the active-surveillance group did (4.1% vs.
0.6%, p < 0.0001; 16.7% vs. 2.8%, p < 0.0001; and 1.6% vs. 0.08%, p < 0.0001,
respectively). Permanent VCP occurred only in two patients (0.2%) in the
immediate surgery group. The proportion of patients on L-thyroxine for
supplemental or thyrotropin (TSH)-suppressive purposes was significantly larger
in the immediate surgery group than in the active surveillance group (66.1% vs.
20.7%, p < 0.0001). The immediate surgery group had significantly higher
incidences of postsurgical hematoma and surgical scar in the neck compared with
the active surveillance group (0.5% vs. 0%, p < 0.05; and 8.0% vs. 100%, p <
0.0001, respectively). CONCLUSIONS: The oncological outcomes of the immediate
surgery and active surveillance groups were similarly excellent, but the
incidences of unfavorable events were definitely higher in the immediate surgery
group. Thus, active surveillance is now recommended as the best choice for
patients with low-risk PMC.
PMID- 26426736
TI - Effect on the Gastrointestinal Absorption of Drugs from Different Classes in the
Biopharmaceutics Classification System, When Treating with Liraglutide.
AB - Like other GLP-1 receptor agonists used for treatment of type 2 diabetes,
liraglutide delays gastric emptying. In this clinical absorption study, the
primary objective was to investigate the effect of liraglutide (at steady state)
on the rate and/or extent of gastrointestinal (GI) absorption of concomitantly
orally taken drugs from three classes of the Biopharmaceutics Classification
System (BCS). To provide a general prediction on liraglutide drug-drug absorption
interaction, single-dose pharmacokinetics of drugs representing BCS classes II
(low solubility-high permeability; atorvastatin 40 mg and griseofulvin 500 mg),
III (high solubility-low permeability; lisinopril 20 mg), and IV (low solubility
low permeability; digoxin 1 mg) were studied in healthy subjects at steady state
of liraglutide 1.8 mg, or placebo, in a two-period crossover design. With
liraglutide, the oral drugs atorvastatin, lisinopril, and digoxin showed delayed
tmax (by <=2 h) and did not meet the criterion for bioequivalence for Cmax
(reduced Cmax by 27-38%); griseofulvin had similar tmax and 37% increased Cmax.
Although the prespecified bioequivalence criterion was not met by all drugs, the
overall plasma exposure (AUC) of griseofulvin, atorvastatin, lisinopril, and
digoxin only exhibited minor changes and was not considered to be of clinical
relevance.
PMID- 26426737
TI - Moving Toward Economically Sustainable Value-Based Cancer Care in the Academic
Setting.
PMID- 26426738
TI - Use of broad-spectrum antibiotics in French EDs: different trends for third
generation cephalosporins and fluoroquinolones.
AB - OBJECTIVES: Third-generation cephalosporins and fluoroquinolones are particularly
prone to promoting bacterial resistance. Their use in Emergency Departments (EDs)
is poorly known. Our objectives were to assess the use of antibacterial agents in
French EDs. METHODS: This study is a retrospective study of antibiotics delivered
to the adult units of 11 EDs of French academic centres in 2012, and to six of
these EDs between 2009 and 2012. RESULTS: The total antibiotic use was 66.4
defined daily doses (DDD)/1000 ED visits in 2012, and it increased between 2009
and 2012 (yearly estimate, +1.8+/-0.9 DDD/1000 ED visits, P=0.048). The 3GC-FQ
class, which grouped third-generation cephalosporins and fluoroquinolones,
accounted for 39.2% of the total antibiotic use, and the use of this class of
antibiotics was highly variable among EDs (range, 31.6-49.5% of total antibiotic
use). The aminopenicillin and beta-lactamase inhibitor/3GC-FQ ratio varied among
EDs [median (range), 0.91 (0.52-1.25)]. Between 2009 and 2012, there was a
significant decrease in the use of the 3GC-FQ class (yearly estimate, -0.8+/-0.4%
of total antibiotic use), antipneumococcal fluoroquinolones (-0.8+/-0.3%) and
other fluoroquinolones (-0.9%+/-0.3%), and there was a significant increase in
the use of third-generation cephalosporins (+0.7+/-0.3%), aminoglycosides (+0.4+/
0.1%), imidazole derivatives (+0.4+/-0.1%) and lincosamides (+0.1+/-0.0%).
CONCLUSION: Fluoroquinolones and third-generation cephalosporins are widely used
in the ED. Their use is highly variable among EDs. Third-generation
cephalosporins were increasingly used between 2009 and 2012, whereas the use of
fluoroquinolones decreased. Reduced use of cephalosporins in the ED, without
increasing fluoroquinolone use, should be aimed at through antibiotic stewardship
programs.
PMID- 26426739
TI - Epidemiology and aetiology of impaired level of consciousness in prehospital
nontrauma patients in an urban setting.
AB - BACKGROUND: There is little information on the epidemiology and aetiology of
nontraumatic loss of consciousness in patients in the Emergency Department, and
this high-risk patient group has been poorly characterized in the prehospital
setting as well. The aim of this study was to study the epidemiology and
aetiology of nontraumatic impaired level of consciousness among the patients
treated by an urban Emergency Medical Service (EMS) system in Finland. METHODS:
Data of all emergency calls not related to trauma in an urban EMS system in
southern Finland during 2012 were analysed. The inclusion criterion in this study
was impaired level of consciousness as identified from the EMS run sheets.
Diagnoses made in the receiving facility were cross-checked with the data.
RESULTS: During the study period, the EMS was alerted to 22 184 emergency calls.
Of these, 306 calls met the inclusion criterion. The included patients could be
categorized into four groups: seizures (32%), diabetes (24%), intoxication (17%)
and impaired level of consciousness with no other obvious or specific cause
(27%). The overall case fatality rate was 8%. CONCLUSION: Of all EMS calls,
patients who presented with an impaired level of consciousness represented 1.4%
of all patients, but the fatality rate in those who remained with an impaired
level of consciousness during the prehospital phase was considerable. Impaired
level of consciousness was associated with a multitude of aetiologies, of which
seizures were the most common.
PMID- 26426740
TI - Catatonia is a systemic medical syndrome.
PMID- 26426742
TI - Visual discrimination of dihydroxybenzene isomers based on a nitrogen-doped
graphene quantum dot-silver nanoparticle hybrid.
AB - A room temperature reducing agent-free strategy for the synthesis of a nitrogen
doped graphene quantum dot-silver nanoparticle (N-GQD/AgNP) hybrid was presented.
In this strategy, N-GQDs were used as a reducing agent and stabilizer for the
formation of the N-GQD/AgNP hybrid, and the formation of the N-GQD/AgNP hybrid
may result from the extraordinary reduction properties of N-GQDs, which are
attributed to the nature of the surface oxygen-containing functional groups. The
N-GQD/AgNP hybrid exhibits good dispersity and outstanding catalytic ability
toward the oxidation of catechol (CC) and hydroquinone (HQ) by Ag(+). In the
presence of the N-GQD/AgNP hybrid, the reduction of Ag(+) by CC and HQ was
improved. CC enhanced the absorbance of the N-GQD/AgNP-Ag(+) system the most, and
HQ followed, while resorcinol (RC) had only a little effect on the absorption
intensity of the system. Thus, a sensitive and selective colorimetric sensing
method based on the N-GQD/AgNP-Ag(+) system was developed for the discrimination
of CC, HQ and RC. A good linear relationship was obtained from 0.1 to 15.0 MUM
for CC and from 0.3 to 20.0 MUM for HQ. The detection limits of CC and HQ were
0.03 and 0.1 MUM, respectively. In addition, the proposed method also shows a
high selectivity for the detection of CC and HQ, and appreciable changes in color
of the N-GQD/AgNP-Ag(+) system toward CC, RC and HQ were observed.
PMID- 26426741
TI - MYC/BCL6 double-hit lymphoma (DHL): a tumour associated with an aggressive
clinical course and poor prognosis.
AB - AIMS: Large B cell lymphomas with MYC and BCL6/3q27 rearrangements, designated
MYC/BCL6 DHL, are uncommon. Our aim was to better characterize this group of
tumours. METHODS AND RESULTS: We studied the clinicopathological features and
outcome of 13 patients with MYC/BCL6 DHL and compared this group to a group of 83
MYC/BCL2 DHL patients. There were eight men and five women, with a median age of
63 years. Eleven tumours were classified as diffuse large B cell lymphomas
(DLBCL) and two were B cell lymphoma, unclassifiable, with features intermediate
between DLBCL and Burkitt lymphoma (BCLU). Immunohistochemical analysis showed
that these tumours were positive for BCL6 (100%), BCL2 (eight of 10; 80%) and
CD10 (eight of 10; 80%). Nine of 12 (75%) cases had a germinal centre B cell
(GCB) immunophenotype; in one case data were incomplete. All patients were
treated with chemotherapy. The clinicopathological features of MYC/BCL6 DHL were
similar to MYC/BCL2 DHL, except that MYC/BCL6 DHL had a GCB immunophenotype less
often. Patients with MYC/BCL6 DHL had a poor overall survival, similar to
patients with MYC/BCL2 DHL (P = 0.32). CONCLUSIONS: MYC/BCL6 DHL is an aggressive
B cell lymphoma and patients often have an aggressive clinical course and poor
prognosis, similar to patients with MYC/BCL2 DHL.
PMID- 26426743
TI - Trajectories of alcohol use and consequences in college women with and without
depressed mood.
AB - College students with depressed mood face heightened risk for experiencing
drinking-related negative consequences. However, few studies have examined
prospective patterns of alcohol consequences among depressed students. In the
present investigation, we assessed how first-year college women's trajectories of
heavy episodic drinking (HED) and alcohol consequences differed as a function of
depressed mood at college entry. Participants were 233 heavy drinking incoming
first-year college females (61% White) at a mid-sized West Coast University.
Participants completed an online baseline survey, attended a single brief group
intervention session, and completed 1- and 6-month post-intervention follow-up
surveys. Depressed mood, alcohol consumption, and alcohol consequences were
assessed at each time point. We employed latent growth curve analyses. Females
with depressed mood, versus without depressed mood, experienced greater levels of
alcohol consequences overall, particularly during transitions to college.
However, contrary to hypotheses, participants with depressed mood (vs. without)
exhibited significantly steeper declining trends in consequences, controlling for
treatment condition, age, race, and ethnicity, and despite stable drinking
levels, depressed mood, and use of protective behaviors over time. Potential
explanations and suggestions for future research are discussed.
PMID- 26426744
TI - Temporal Profile of MicroRNA Expression in Contused Cortex after Traumatic Brain
Injury in Mice.
AB - MicroRNAs (miRNAs) were recently identified as important regulators of gene
expression under a wide range of physiological and pathophysiological conditions.
Thus, they may represent a novel class of molecular targets for the management of
traumatic brain injury (TBI). In this study, we investigated the temporal profile
of miRNA expression during the development of secondary brain damage after
experimental TBI. For this purpose, we used a controlled cortical impact model in
C57Bl/6 mice (n = 6) to induce a cortical contusion and analyzed miRNA expression
in the traumatized cortex by microarray analysis during the development of
secondary contusion expansion-i.e., at 1, 6, and 12 h after TBI. Of a total 780
mature miRNA sequences analyzed, 410 were detected in all experimental groups. Of
these, 158 miRNAs were significantly upregulated or downregulated in TBI compared
with sham-operated animals, and 52 miRNAs increased more than twofold. We
validated the upregulation of five of the most differentially expressed miRNAs
(miR-21*, miR-144, miR-184, miR-451, miR-2137) and the downregulation of four of
the most differentially expressed miRNAs (miR-107, miR-137, miR-190, miR-541) by
quantitative polymerase chain reaction (qPCR). miR-2137, the most differentially
expressed miRNA after TBI, was further investigated by in situ hybridization and
was found to be upregulated in neurons within the traumatic penumbra. This study
gives a comprehensive picture of miRNA expression levels during secondary
contusion expansion after TBI and may pave the way for the identification of
novel targets for the management of brain trauma.
PMID- 26426745
TI - Group 13 complexes of dipyridylmethane, a forgotten ligand in coordination
chemistry.
AB - The reactions of dipyridylmethane (dpma) with group 13 trichlorides were
investigated in 1 : 1 and 1 : 2 molar ratios using NMR spectroscopy and X-ray
crystallography. With 1 : 1 stoichiometry and Et2O as solvent, reactions
employing AlCl3 or GaCl3 gave mixtures of products with the salt
[(dpma)2MCl2](+)[MCl4](-) (M = Al, Ga) as the main species. The corresponding
reactions in 1 : 2 molar ratio gave similar mixtures but with
[(dpma)MCl2](+)[MCl4](-) as the primary product. Pure salts [(dpma)AlCl2](+)[Cl](
) and [(dpma)AlCl2](+)[AlCl4](-) could be obtained by performing the reactions in
CH3CN. In the case of InCl3, a neutral monoadduct (dpma)InCl3 formed regardless
of the stoichiometry employed. A neutral adduct (dpma)(BCl3)2 was obtained from
the reaction between dpma and BCl3 in Et2O using 1 : 2 stoichiometry. With 1 : 1
molar ratio of reagents, a mixture of products and deprotonation of the methylene
bridge in [(dpma)BCl2](+) was observed. The experimental data showed that the
structural flexibility of the dpma ligand results in more diverse coordination
chemistry with group 13 elements than that observed for bipyridine (bpy), while
computational investigations indicated that the investigated metal-ligand
interactions are, to a first approximation, independent of the ligand type.
Electrochemical and chemical attempts to reduce the cations [(dpma)MCl2](+)
showed that, in stark contrast to the chemistry of the related [(bpy)BCl2](+)
cation, the neutral radicals [(dpma)MCl2] are extremely unstable. Differences in
the redox behaviour of dpma and bpy could be rationalized with the electronic
structure of the ligand and that of the methylene bridge in particular. As a
whole, the facile reactivity of the methylene bridge in the dpma ligand renders
it amenable to further reactivity and functionalization that is not possible in
the case of bpy.
PMID- 26426746
TI - Holey Graphene as a Weed Barrier for Molecules.
AB - We demonstrate the use of "holey" graphene as a mask against molecular
adsorption. Prepared porous graphene is transferred onto a Au{111} substrate,
annealed, and then exposed to dilute solutions of 1-adamantanethiol. In the pores
of the graphene lattice, we find islands of organized, self-assembled molecules.
The bare Au in the pores can be regenerated by postdeposition annealing, and new
molecules can be self-assembled in the exposed Au region. Graphene can serve as a
robust, patternable mask against the deposition of self-assembled monolayers.
PMID- 26426747
TI - Plasma Exosomal miRNAs in Persons with and without Alzheimer Disease: Altered
Expression and Prospects for Biomarkers.
AB - To assess the value of exosomal miRNAs as biomarkers for Alzheimer disease (AD),
the expression of microRNAs was measured in a plasma fraction enriched in
exosomes by differential centrifugation, using Illumina deep sequencing. Samples
from 35 persons with a clinical diagnosis of AD dementia were compared to 35 age
and sex matched controls. Although these samples contained less than 0.1
microgram of total RNA, deep sequencing gave reliable and informative results.
Twenty miRNAs showed significant differences in the AD group in initial screening
(miR-23b-3p, miR-24-3p, miR-29b-3p, miR-125b-5p, miR-138-5p, miR-139-5p, miR-141
3p, miR-150-5p, miR-152-3p, miR-185-5p, miR-338-3p, miR-342-3p, miR-342-5p, miR
548at-5p, miR-659-5p, miR-3065-5p, miR-3613-3p, miR-3916, miR-4772-3p, miR-5001
3p), many of which satisfied additional biological and statistical criteria, and
among which a panel of seven miRNAs were highly informative in a machine learning
model for predicting AD status of individual samples with 83-89% accuracy. This
performance is not due to over-fitting, because a) we used separate samples for
training and testing, and b) similar performance was achieved when tested on
technical replicate data. Perhaps the most interesting single miRNA was miR-342
3p, which was a) expressed in the AD group at about 60% of control levels, b)
highly correlated with several of the other miRNAs that were significantly down
regulated in AD, and c) was also reported to be down-regulated in AD in two
previous studies. The findings warrant replication and follow-up with a larger
cohort of patients and controls who have been carefully characterized in terms of
cognitive and imaging data, other biomarkers (e.g., CSF amyloid and tau levels)
and risk factors (e.g., apoE4 status), and who are sampled repeatedly over time.
Integrating miRNA expression data with other data is likely to provide
informative and robust biomarkers in Alzheimer disease.
PMID- 26426748
TI - Quantitative-profiling of neurotransmitter abnormalities in the disease
progression of experimental diabetic encephalopathy rat.
AB - Diabetic encephalopathy (DE) is one of the most prevalent chronic complications
of diabetes mellitus (DM), with neither effective prevention nor proven
therapeutic regimen. This study aims to uncover the potential dysregulation
pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced
experimental DE. For that purpose, male Sprague-Dawley (SD) rats were treated
with a single intraperitoneal injection of STZ. Cognitive performance was
detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF),
and brain tissues were collected to measure the levels of neurotransmitters.
Compared with the control rats, the acetylcholine (ACh) levels in serum, CSF,
hippocampus, and cortex were all significantly down-regulated as early as 6 weeks
in the STZ treatment group. In contrast, the glutamate (Glu) levels were
decreased in CSF and the hippocampus, but unaffected in the serum and cortex of
STZ-treated rats. As for gamma-aminobutyric acid (GABA), it was down-regulated in
serum, but up-regulated in CSF, hippocampus, and the cortex in the STZ-treated
group. The mRNA expressions of neurotransmitter-related rate limiting enzymes
(including AChE, GAD1, and GAD2) and pro-inflammatory cytokines (including IL
1beta and TNF-alpha) were all increased in the DE rats. Our data suggest that DM
induces isoform-dependent and tissue-specific neurotransmitter abnormalities, and
that neuroinflammation may underlay the nervous system dysfunction observed in
the progression of DE.
PMID- 26426757
TI - Ten Simple Rules for Protecting Research Integrity.
PMID- 26426758
TI - Imaging the behavior of molecules in biological systems: breaking the 3D speed
barrier with 3D multi-resolution microscopy.
AB - The overwhelming effort in the development of new microscopy methods has been
focused on increasing the spatial and temporal resolution in all three dimensions
to enable the measurement of the molecular scale phenomena at the heart of
biological processes. However, there exists a significant speed barrier to
existing 3D imaging methods, which is associated with the overhead required to
image large volumes. This overhead can be overcome to provide nearly unlimited
temporal precision by simply focusing on a single molecule or particle via real
time 3D single-particle tracking and the newly developed 3D Multi-resolution
Microscopy (3D-MM). Here, we investigate the optical and mechanical limits of
real-time 3D single-particle tracking in the context of other methods. In
particular, we investigate the use of an optical cantilever for position
sensitive detection, finding that this method yields system magnifications of
over 3000*. We also investigate the ideal PID control parameters and their effect
on the power spectrum of simulated trajectories. Taken together, these data
suggest that the speed limit in real-time 3D single particle-tracking is a result
of slow piezoelectric stage response as opposed to optical sensitivity or PID
control.
PMID- 26426759
TI - Photohole Induced Corrosion of Titanium Dioxide: Mechanism and Solutions.
AB - Titanium dioxide (TiO2) has been extensively investigated as photoanode for water
oxidation, as it is believed to be one of the most stable photoanode materials.
Yet, we surprisingly found that TiO2 photoanodes (rutile nanowire, anatase
nanotube, and P25 nanoparticle film) suffered from substantial photocurrent decay
in neutral (Na2SO4) as well as basic (KOH) electrolyte solution.
Photoelectrochemical measurements togehter with electron microscopy studies
performed on rutile TiO2 nanowire photoanode show that the photocurrent decay is
due to photohole induced corrosion, which competes with water oxidation reaction.
Further studies reveal that photocurrent decay profile in neutral and basic
solutions are fundamentally different. Notably, the structural reconstruction of
nanowire surface occurs simultaneously with the corrosion of TiO2 in KOH solution
resulting in the formation of an amorphous layer of titanium hydroxide, which
slows down the photocorrosion. Based on this discovery, we demonstrate that the
photoelectrochemical stability of TiO2 photoanode can be significantly improved
by intentionally coating an amorphous layer of titanium hydroxide on the nanowire
surface. The pretreated TiO2 photaonode exhibits an excellent photocurrent
retention rate of 97% after testing in KOH solution for 72 h, while in comparison
the untreated sample lost 10-20% of photocurrent in 12 h under the same
measurement conditions. This work provides new insights in understanding of the
photoelectrochemical stability of bare TiO2 photoanodes.
PMID- 26426761
TI - Staging and therapy for patients with hepatocellular cancer in a defined
population from 2000 to 2011 - active palliative treatment improved overall
survival.
AB - BACKGROUND: Sweden's western region has successively introduced the use of
validated non-invasive diagnostic algorithms and treatment allocation for
hepatocellular cancer (HCC). The aim was to analyse whether between 2000 and 2011
these changes in strategy had an impact on survival. METHODS: Data concerning
diagnosis, survival and treatment for 687 individuals with HCC were retrieved
from the regional cancer centre's register and hospital charts. The 12-year
period was divided into three four-year cohorts (A-B-C). RESULTS: There was an
increase in the crude incidence rate of HCC from 2.7 to 4.2 per 100 000
inhabitants (p < 0.0001) over the period studied. Imaging was increasingly used
for diagnosis over the three time periods (1.4%, 7.9% and 29%; p < 0.0001).
Alcohol abuse was the most common aetiology for underlying liver disease (42%).
The median survival time for all HCC patients improved over time - period A: 3.8
months, period B: 5.1 months and period C: 7.0 months (p = 0.0007). The 209
patients without any underlying liver disease had a worse survival than the 377
with a reported underlying liver disease (p = 0.0001). Active palliative
treatment (APT) increased from 17% to 35% during period C (p < 0.0001). For these
patients, median survival increased from 8.8 months to 14.2 months. Best
supportive care was used less over time. DISCUSSION: Overall survival improved
when more patients had APT, mainly trans arterial chemoembolisation (TACE).
PMID- 26426760
TI - Emerging roles for the FBXW7 ubiquitin ligase in leukemia and beyond.
AB - Protein degradation plays key roles in diverse pathways in cell division, growth
and differentiation. Aberrant stabilization of crucial proteins participating in
oncogenic pathways is often observed in cancer. The importance of proper protein
turnover is exemplified by the SCF(Fbxw7) ubiquitin ligase, which is frequently
mutated in human cancer, including T cell acute lymphoblastic leukemia. Recent
studies have revealed novel substrates of Fbxw7 and shed light on its role on
differentiation of stem cells and expansion of stem-cell-like cells driving
tumorigenesis. Detailed understanding of the contribution of the Fbxw7-regulated
network of proteins in initiation and progression of cancer will facilitate the
identification of candidate intervention targets in human cancer.
PMID- 26426762
TI - Skin self-examination behaviors among individuals diagnosed with melanoma.
AB - Many melanoma patients do not regularly perform thorough skin self-examinations.
We examined the extent to which melanoma patients conduct thorough skin self
examination, how they perform skin self-examination, and their related knowledge
and self-efficacy. A sample of 176 individuals (61.5% response rate) diagnosed
with primary pathologic stage 0-III cutaneous malignant melanoma at a single
cancer center completed a written or telephone survey regarding their skin self
examination behaviors and associated factors. Almost all participants (98.9%)
reported their race as white. Almost three-quarters (71.6%) of participants
reported doing an examination in the past 2 months. However, only 14.2% had
examined all areas of the body in the past 2 months. Few participants reported
always using a full-length mirror (13.4%), hand-held mirror (11.3%), or having
someone help (9.2%) when doing an examination. Having a higher level of
education, greater knowledge of the ABCDE rule for detecting potential melanoma,
higher skin self-examination self-efficacy, being shown how to do skin self
examination, and being shown what a suspicious mole would look like were all
significantly associated with conducting more thorough skin self-examination.
Most melanoma patients do not engage in regular, thorough skin self-examination,
and when they do examine their skin they typically do not sufficiently utilize
tools and techniques to facilitate a thorough examination and tracking of
potentially suspicious moles. Efforts to promote skin self-examination among
melanoma patients should focus on increasing knowledge and self-efficacy and
providing education about the why, when, and how of conducting self-examination
and mole tracking.
PMID- 26426763
TI - Computer-assisted melanoma diagnosis: a new integrated system.
AB - In dermatology, attempts at synergy between man and machine have mainly been made
to improve melanoma diagnosis. The aim of the present study was to test an
'integrated digital dermoscopy analysis' (i-DDA) system with a series of
melanocytic lesions that were benign and malignant in nature, and to evaluate its
discriminating power with respect to histological diagnosis. In a retrospective
study we used an i-DDA system to evaluate a series of 856 excised, clinically
atypical pigmented skin lesions (584 benign and 272 malignant). The system
evaluated 48 parameters to be studied as possible discriminant variables, grouped
into four categories (geometries, colours, textures and islands of colour)
integrated with three personal metadata items (sex, age and site of lesion) and
presence/absence of three dermoscopic patterns (regression structures, blue-white
veil and polymorphic vascular structures). Stepwise multivariate logistic
regression of i-DDA data selected nine variables with the highest possible
discriminant power. At the end of the stepwise procedure the percentage of cases
correctly classified by i-DDA was 89.2% (100% sensitivity and 40.8% specificity).
The limitations of the study included those associated with a retrospective
design and the 'a priori' exclusion of nonmelanocytic skin lesions. By
incorporating numerical digital features with personal data and some dermoscopic
patterns into the learning process, the proposed i-DDA improved the performance
of assisted melanoma diagnosis, with the advantage that our results can be
objectively repeated in any other clinical setting.
PMID- 26426764
TI - Integrating first-line treatment options into clinical practice: what's new in
advanced melanoma?
AB - Melanoma remains a serious form of skin cancer in Europe and worldwide.
Localized, early-stage melanomas can usually be treated with surgical excision.
However, the prognosis is poorer for patients with advanced disease. Before 2011,
treatment for advanced melanoma included palliative surgery and/or radiotherapy,
and chemotherapy with or without immunotherapy, such as interleukin-2. As none of
these treatments had shown survival benefits in patients with advanced melanoma,
European guidelines had recommended that patients be entered into clinical
trials. The lack of approved first-line options and varying access to clinical
trials meant that European clinicians relied on experimental regimens and
chemotherapy-based treatments when no other options were available. Since 2011,
ipilimumab, an immuno-oncology therapy, and vemurafenib and dabrafenib, targeted
agents that inhibit mutant BRAF, have been approved by the European Medicines
Agency for the treatment of advanced melanoma. More recently, the MEK inhibitor,
trametinib, received European marketing authorization for use in patients with
BRAF mutation-positive advanced melanoma. In 2014, the anti-PD-1 antibody
nivolumab was approved as a first-line therapy in Japan. Whereas nivolumab and
another anti-PD-1 antibody, pembrolizumab, were approved as second-line therapies
in the USA, their recent approval in Europe are for first-line use based on new
clinical trial data in this setting. Together these agents are changing clinical
practice and making therapeutic decisions more complex. Here, we discuss current
and emerging therapeutic options for the first-line treatment of advanced
melanoma, and how these therapies can be optimized to provide the best possible
outcomes for patients.
PMID- 26426765
TI - Decreased expression of class III beta-tubulin is associated with unfavourable
prognosis in patients with malignant melanoma.
AB - Class III beta-tubulin (TUBB3) has been recognized as being associated with
resistance to taxane-based regimens in several cancers. However, little is known
about the clinicopathological significance of TUBB3 expression in patients with
cutaneous malignant melanoma. The aim of this study was to examine the prognostic
significance of TUBB3 expression in cutaneous malignant melanoma. A total of 106
patients with surgically resected cutaneous malignant melanoma were assessed.
Tumour sections were immunohistochemically stained for TUBB3, Ki-67 and
microvessel density with CD34. TUBB3 was highly expressed in 80% (85/106) of
patients. No statistically significant relationship was observed between the high
expression of TUBB3 and any variables. On univariate analysis, ulceration,
disease stage, TUBB3 and CD34 revealed a significant relationship with overall
survival and progression-free survival. Multivariate analysis confirmed that a
low TUBB3 expression was an independent prognostic factor for poor prognosis of
cutaneous malignant melanoma. The decreased expression of TUBB3 could be a
significant marker for predicting unfavourable prognosis in patients with
cutaneous malignant melanoma.
PMID- 26426766
TI - Interaction of NBD-labelled fatty amines with liquid-ordered membranes: a
combined molecular dynamics simulation and fluorescence spectroscopy study.
AB - A complete homologous series of fluorescent 7-nitrobenz-2-oxa-1,3-diazol-4-yl
(NBD) labelled fatty amines of varying alkyl chain lengths, NBD-Cn, inserted in 1
palmitoyl, 2-oleoyl-sn-glycero-3-phosphocholine (POPC) or N-palmitoyl
sphingomyelin (SpM) bilayers, with 50 mol% and 40 mol% cholesterol (Chol),
respectively, was studied using atomistic molecular dynamics simulations. For all
amphiphiles in both bilayers, the NBD fluorophore locates at the interface, in a
more external position than that previously observed for pure POPC bilayers. This
shallower location of the NBD group agrees with the lower fluorescent quantum
yield, shorter fluorescence lifetime, and higher ionisation constants (smaller
pKa) determined experimentally. The more external location is also consistent
with the changes measured in steady-state fluorescence anisotropy from POPC to
POPC/Chol (1 : 1) vesicles. Accordingly, the equilibrium location of the NBD
group within the various bilayers is mainly dictated by bilayer compositions, and
is mostly unaffected by the length of the attached alkyl chain. Similarly to the
behaviour observed in POPC bilayers, the longer-chained NBD-Cn amphiphiles show
significant mass density near the mixed bilayers' midplanes, and the alkyl chains
of the longer derivatives, mainly NBD-C16, penetrate the opposite bilayer leaflet
to some extent. However, this effect is quantitatively less pronounced in these
ordered bilayers than in POPC. Similarly to POPC bilayers, the effects of these
amphiphiles on the structure and dynamics of the host lipid were found to be
relatively mild, in comparison with acyl-chain phospholipid analogues.
PMID- 26426767
TI - Correction to Fidelity of RNA Polymerase II Transcription: Role of Rpb9 in Error
Detection and Proofreading.
PMID- 26426768
TI - Affair With Triphasic Waves-Their Striking Presence, Mysterious Significance, and
Cryptic Origins: What are They?
AB - Triphasic waves, which have been recorded in the EEG of encephalopathy for more
than 50 years, remain clearly identifiable but historically purportedly of
uncertain significance. Initially described with liver failure and high serum
ammonias, they came to be reported in an ever-expanding list of metabolic, toxic,
and structural conditions. Often a dynamic finding (in which the occurrence of
triphasic waves might increase or decrease with stimulation or arousal of the
patient during EEG), there has been increasing insight into their correlation
with multiple concurrent conditions, including subcortical white-matter disease,
infections and metabolic disturbances, and their prognostic significance. There
are sparse data, but there is active controversy into their confusion for, or
occurrence in, nonconvulsive status epilepticus. This review and commentary
discuss our current understanding of triphasic waves and the newer areas of
contention surrounding this mysterious EEG morphology.
PMID- 26426769
TI - Day-Night Patterns of Epileptiform Activity in 65 Patients With Long-Term
Ambulatory Electrocorticography.
AB - PURPOSE: To characterize cyclic day-night patterns of electrocorticographic
epileptiform activity (EA) in patients with focal onset seizures. METHODS:
Epileptiform events as defined by the physician (also termed more generally as
"epileptiform activity" or EA) were recorded in 65 patients with partial onset
(also referred to as "focal onset") seizures using the RNS System, which includes
a cranially implanted neurostimulator connected to 1 or two 4-contact leads
placed at the seizure focus. The neurostimulator is programmed to detect specific
patterns of electrocorticographic activity and to provide responsive stimulation.
The 24-hour periodicity of detections of EA was analyzed for individual patients
and for subgroups of patients according to the type of EA, laterality, lobe of
onset, and whether the onset was neocortical or hippocampal. The time of day when
peaks in EA occurred was also analyzed. RESULTS: There were robust circadian
patterns of detections of EA in most patients, with a primary peak in detections
at night and a secondary peak in the late afternoon in some cases. Subset
analyses were performed by lobe, region of the brain, and type of cortex
(neocortical vs. hippocampal); significant circadian rhythmicity was present in
all subsets. CONCLUSIONS: This is the first report of circadian cycles of EA as
assessed through chronic ambulatory electrocorticographic recordings in adults
with focal onset seizures. Epileptiform activity displayed circadian patterns in
the majority of these patients. These findings suggest that epilepsy therapies
might be optimized by adjusting the timing of therapy according to each patient's
unique circadian pattern of EA.
PMID- 26426770
TI - Clinical and Imaging Correlations of Generalized Hypersynchronous Alpha Activity
in Human EEG Recordings, During Alertness.
AB - PURPOSE: In a considerable percentage of individuals with a detectable alpha
rhythm in their EEG, bursts of generalized hypersynchronous alpha activity
(GHSAA) may occur, during alertness. The aim of this study was to examine whether
appearance of GHSAA, which probably generates from transcortical circuitry, shows
any correlation with demographic characteristics, underlying normal or abnormal
pathophysiology, or substances in use. METHODS: The authors retrospectively
reviewed 441 EEG recordings performed in their laboratory during a 1-year period
for presence of GHSAA, concomitantly collecting data that concerned symptoms,
diagnosis, imaging, medication, and demographics. Recordings in mental states
other than alertness were excluded from the sample. RESULTS: Generalized
hypersynchronous alpha activity was found in 22.95% of the study population. Its
occurrence was diminished in male gender (P < 0.001), older age (Kendall tau,
0.16; P < 0.0001), and disorders involving structural abnormalities like brain
lesions or neurodegeneration (P < 0.02). Dementia, Parkinson disease, and
psychoses showed individually a trend towards lower GHSAA presence. CONCLUSIONS:
In the sample, the presence of GHSAA was commonly observed in the cohort of
patients without abnormalities in their neuroimaging studies. Generalized
hypersynchronous alpha activity is a finding of youth and requires a properly
functioning cerebral cortex in order to emerge. Female preponderance may signify
underlying trangender differences in alpha rhythm generators. These preliminary
results indicate that the significance of GHSAA alterations deserves more
thorough evaluation in larger groups of patients suffering from a variety of
different neuropsychiatric disorders.
PMID- 26426771
TI - Author Response: Concerns About Utility and Cost-Effectiveness of Continuous
Critical-Care EEG.
PMID- 26426772
TI - Author Response: The Timing of Continuous EEG in Critically Ill Patients: Stat?
ASAP? Routine?
PMID- 26426773
TI - Dengue in the State of Rio Grande do Norte, Brazil, 2010-2012.
AB - OBJECTIVE: To present results of virological surveillance and epidemiological
aspects of dengue in the State of Rio Grande do Norte, Brazil. METHODS: A total
of 1581 cases, reported from 2010 to 2012 at various health centres in the state,
were analysed by viral isolation and/or RT-PCR for viral detection and typing. To
identify whether different genotypes were circulating in the state during this
period, sequencing of the complete E gene for DENV (1485 bp in length) was
performed directly from patient serum samples. RESULTS: All four serotypes of
dengue virus circulated in Rio Grande do Norte, with the introduction of DENV-4
in the state in 2011. In 2012, DENV-4 represented 100% of positive confirmed
cases. 53.97% of cases occurred in Natal. Case numbers peaked in April (21%) and
May (23%). Genetic characterisation of circulating strains confirmed the
circulation of genotypes V, south-east Asian/American and II, respectively, for
DENV-1, DENV-2 and DENV-4. CONCLUSIONS: This work furthers a better understanding
of dengue viruses in the State of Rio Grande do Norte. Strengthening control
efforts in the region is important considering the impact of dengue.
PMID- 26426777
TI - Single-Molecule Spin Switch Based on Voltage-Triggered Distortion of the
Coordination Sphere.
AB - Here, we report on a new single-molecule-switching concept based on the
coordination-sphere-dependent spin state of Fe(II) species. The perpendicular
arrangement of two terpyridine (tpy) ligands within heteroleptic complexes is
distorted by the applied electric field. Whereas one ligand fixes the complex in
the junction, the second one exhibits an intrinsic dipole moment which senses the
E field and causes the distortion of the Fe(II) coordination sphere triggering
the alteration of its spin state. A series of complexes with different dipole
moments have been synthesized and their transport features were investigated via
mechanically controlled break-junctions. Statistical analyses support the
hypothesized switching mechanism with increasing numbers of junctions displaying
voltage-dependent bistabilities upon increasing the Fe(II) complexes' intrinsic
dipole moments. A constant threshold value of the E field required for switching
corroborates the mechanism.
PMID- 26426778
TI - Fetal cerebellar hemorrhage: three cases with postnatal follow-up.
PMID- 26426779
TI - Is genomic medicine finally coming of age for the diagnosis of pneumonia?
PMID- 26426780
TI - The evidence for long-term benefits of restoration of CFTR function continues to
grow.
PMID- 26426781
TI - A milestone in the investigation of population-wide effects of vaccines.
PMID- 26426782
TI - Bone morphogenetic protein receptor type II and inflammation are bringing old
concepts into the new pulmonary arterial hypertension world.
PMID- 26426783
TI - Is the kidney yet another potential end-organ casualty of obstructive sleep
apnea?
PMID- 26426784
TI - Update in Mycobacterium tuberculosis lung disease 2014.
PMID- 26426786
TI - Surgical masks reduce airborne spread of Pseudomonas aeruginosa in colonized
patients with cystic fibrosis.
PMID- 26426787
TI - Risk factors for frequent severe exacerbations in late-onset eosinophilic asthma.
PMID- 26426785
TI - An official American Thoracic Society/American College of Chest Physicians policy
statement: implementation of low-dose computed tomography lung cancer screening
programs in clinical practice.
AB - RATIONALE: Annual low-radiation-dose computed tomography (LDCT) screening for
lung cancer has been shown to reduce lung cancer mortality among high-risk
individuals and is now recommended by multiple organizations. However, LDCT
screening is complex, and implementation requires careful planning to ensure
benefits outweigh harms. Little guidance has been provided for sites wishing to
develop and implement lung cancer screening programs. OBJECTIVES: To promote
successful implementation of comprehensive LDCT screening programs that are safe,
effective, and sustainable. METHODS: The American Thoracic Society (ATS) and
American College of Chest Physicians (ACCP) convened a committee with expertise
in lung cancer screening, pulmonary nodule evaluation, and implementation
science. The committee reviewed the evidence from systematic reviews, clinical
practice guidelines, surveys, and the experience of early-adopting LDCT screening
programs and summarized potential strategies to implement LDCT screening programs
successfully. MEASUREMENTS AND MAIN RESULTS: We address steps that sites should
consider during the main three phases of developing an LDCT screening program:
planning, implementation, and maintenance. We present multiple strategies to
implement the nine core elements of comprehensive lung cancer screening programs
enumerated in a recent ACCP/ATS statement, which will allow sites to select the
strategy that best fits with their local context and workflow patterns. Although
we do not comment on cost-effectiveness of LDCT screening, we outline the
necessary costs associated with starting and sustaining a high-quality LDCT
screening program. CONCLUSIONS: Following the strategies delineated in this
policy statement may help sites to develop comprehensive LDCT screening programs
that are safe and effective.
PMID- 26426788
TI - The forgotten era of medical discoveries.
PMID- 26426789
TI - The lung immune response to bacteria in chronic obstructive pulmonary disease.
PMID- 26426790
TI - Reply: the lung immune response to bacteria in chronic obstructive pulmonary
disease.
PMID- 26426791
TI - Understanding the anatomic basis for obstructive sleep apnea syndrome in
adolescents: how to proceed?
PMID- 26426792
TI - Reply: understanding the anatomic basis for obstructive sleep apnea syndrome in
adolescents: how to proceed?
PMID- 26426793
TI - Continuous positive airway pressure-emergent protracted central apneas with
profound oxygen desaturation.
PMID- 26426794
TI - What is lung transplantation?
PMID- 26426795
TI - IL-2 and IL-15 regulate CD8+ memory T-cell differentiation but are dispensable
for protective recall responses.
AB - The ability to mount effective secondary responses is a cardinal feature of
memory CD8(+) T cells. An understanding of the factors that regulate the
generation and recall capacities of memory T cells remains to be ascertained.
Several cues indicate that two highly related cytokines, IL-2 and IL-15, share
redundant functions in this process. To establish their combined roles in memory
CD8(+) T-cell development, maintenance, and secondary responses, we compared the
outcome of adoptively transferred IL2Rbeta(+/-) or IL2Rbeta(-/-) CD8(+) T cells
after an acute viral infection in mice. Our results demonstrate that both IL-2
and IL-15 signals condition the differentiation of primary and secondary short
lived effector cells by altering the transcriptional network governing lineage
choices. These two cytokines also regulate the homeostasis of the memory T-cell
pool, with effector memory CD8(+) T cells being the most sensitive to these two
interleukins. Noticeably, the inability to respond to both cytokines limits the
proliferation and survival of primary and secondary effectors cells, whereas it
does not preclude potent cytotoxic functions and viral control either initially
or upon rechallenge. Globally, these results indicate that lack of IL-2 and IL-15
signaling modulates the CD8(+) T-cell differentiation program but does not impede
adequate effector functions.
PMID- 26426796
TI - Similar Reduction of Cholesterol-Adjusted Vitamin E Serum Levels in Simple
Steatosis and Non-Alcoholic Steatohepatitis.
AB - OBJECTIVES: Reduced vitamin E levels have been reported in patients with non
alcoholic steatohepatitis (NASH), but no conclusive data on patients with simple
steatosis (SS) are available. Aim of this study was to investigate the
association between serum vitamin E levels and SS. METHODS: A cohort of 312
patients with cardio-metabolic risk factors was screened for liver steatosis by
ultrasonography (US). We reasonably classified as SS patients with US-fatty
liver, normal liver function tests (LFTs) and with Cytokeratin 18 <246 mIU/ml.
Liver biopsy was performed in 41 patients with US-fatty liver and persistent
elevation of LFTs (>6 months). Serum cholesterol-adjusted vitamin E (Vit E/chol)
levels were measured. RESULTS: Mean age was 53.9+/-12.5 years and 38.4% were
women. Non-alcoholic fatty liver disease (NAFLD) was detected at US in 244
patients; of those 39 had biopsy-proven NASH and 2 borderline NASH. Vit E/chol
was reduced in both SS (3.4+/-2.0, P<0.001), and NASH (3.5+/-2.1, P=0.006)
compared with non-NAFLD patients (4.8+/-2.0 MUmol/mmol chol). No difference was
found between SS and NASH (P=0.785). After excluding patients with NASH, a
multivariable logistic regression analysis found that Vit E/chol (odds ratio
(OR): 0.716, 95% confidence interval (CI) 0.602-0.851, P<0.001), alanine
aminotransferase (ALT, OR: 1.093, 95% CI 1.029-1.161, P=0.004), body mass index
(OR: 1.162, 95% CI 1.055-1.279, P=0.002) and metabolic syndrome (OR: 5.725, 95%
CI 2.247-14.591, P<0.001) were factors independently associated with the presence
of SS. CONCLUSIONS: Reduced vitamin E serum levels are associated with SS, with a
similar reduction between patients with SS and NASH, compared with non-NAFLD
patients. Our findings suggest that the potential benefit of vitamin E
supplementation should be investigated also in patients with SS.
PMID- 26426797
TI - Prenatal diagnosis and outcomes of fetal teratomas.
AB - PURPOSE: Our aim was to evaluate the diagnostic performance of ultrasonography
(US) in the prenatal identification of teratomas and the perinatal outcome of the
fetuses with those teratomas. METHODS: In this retrospective case series study,
we searched the archives using the keywords "fetal mass" or "fetal tumor" or
"fetal teratoma" and "sacrococcygeal teratoma," diagnosed between 2009 and 2014,
within the US database of our center. RESULTS: One hundred seven fetuses were
prenatally diagnosed as having a cystic or solid mass, tumor, or teratoma.
Nineteen of those cases were diagnosed prenatally as having fetal teratoma, but
that diagnosis could not be verified in three cases. In one fetus, the prenatal
diagnosis could not be confirmed. The sensitivity of US in identifying fetal
teratoma was 100% and the false-positive rate, 3.3%. Six pregnancies complicated
by a fetal teratoma were terminated. A normal karyotype was identified in all
fetuses that underwent karyotyping. Among the nine women who continued their
pregnancy, polyhydramnios was identified in four fetuses; although high-output
heart failure was also identified in two of those fetuses during prenatal follow
up, none developed hydrops. On delivery, nine infants were born alive, but three
(33.3%) of them died within the early neonatal period. CONCLUSIONS: US has very
high sensitivity and low false-positive rates in identifying fetal teratoma
prenatally. The risk of chromosomal abnormalities is very low in fetuses with
teratoma, and their prognosis depends on the location and size of the tumor and
any associated perinatal complications.
PMID- 26426798
TI - A Multiple Regression Approach to Normalization of Spatiotemporal Gait Features.
AB - Normalization of gait data is performed to reduce the effects of intersubject
variations due to physical characteristics. This study reports a multiple
regression normalization approach for spatiotemporal gait data that takes into
account intersubject variations in self-selected walking speed and physical
properties including age, height, body mass, and sex. Spatiotemporal gait data
including stride length, cadence, stance time, double support time, and stride
time were obtained from healthy subjects including 782 children, 71 adults, 29
elderly subjects, and 28 elderly Parkinson's disease (PD) patients. Data were
normalized using standard dimensionless equations, a detrending method, and a
multiple regression approach. After normalization using dimensionless equations
and the detrending method, weak to moderate correlations between walking speed,
physical properties, and spatiotemporal gait features were observed (0.01 < |r| <
0.88), whereas normalization using the multiple regression method reduced these
correlations to weak values (|r| <0.29). Data normalization using dimensionless
equations and detrending resulted in significant differences in stride length and
double support time of PD patients; however the multiple regression approach
revealed significant differences in these features as well as in cadence, stance
time, and stride time. The proposed multiple regression normalization may be
useful in machine learning, gait classification, and clinical evaluation of
pathological gait patterns.
PMID- 26426799
TI - Patterns of Sensitization to Inhalant Allergens in Japanese Lower-Grade
Schoolchildren and Related Factors.
AB - OBJECTIVE: This study clarified sensitization patterns to house dust mite (HDM)
and Japanese cedar pollen (JCP) in Japanese lower-grade schoolchildren. We also
explored factors associated with allergic sensitization. METHODS: This cross
sectional study used a database from the Study on Respiratory Disease and
Automobile Exhaust (SORA), a Japanese health study project. The subjects
comprised 8,815 pupils aged 6-9 years. We obtained the distribution of HDM- and
JCP-specific IgE, respectively, as a marker of sensitization. To determine
factors associated with sensitization, we used logistic regression and calculated
adjusted odds ratios (AORs) for the relative prevalence of sensitization. The cut
off point for specific IgE levels was 0.35 kU/l. RESULTS: Sensitization to HDM
and JCP was detected in 51 and 39% of subjects, respectively, occurring more
often in boys and at older ages. In addition, AORs of sensitization to HDM/JCP
were higher in subjects with a history of bronchitis, parental asthma, parental
atopic eczema and parental pollinosis. In contrast, AORs for sensitization were
lower in those subjected to maternal passive smoking as well as among boys with
pets. AORs of sensitization to JCP alone were lower in those with a history of
otitis media, those who had been bottle milk fed, and those who were not the
firstborn and who lived near a busy road. CONCLUSION: Sensitization to HDM and
JCP was detected in 51 and 39% of lower-grade schoolchildren, respectively.
PMID- 26426800
TI - Complete Plastid Genome Sequence of the Brown Alga Undaria pinnatifida.
AB - In this study, we fully sequenced the circular plastid genome of a brown alga,
Undaria pinnatifida. The genome is 130,383 base pairs (bp) in size; it contains a
large single-copy (LSC, 76,598 bp) and a small single-copy region (SSC, 42,977
bp), separated by two inverted repeats (IRa and IRb: 5,404 bp). The genome
contains 139 protein-coding, 28 tRNA, and 6 rRNA genes; none of these genes
contains introns. Organization and gene contents of the U. pinnatifida plastid
genome were similar to those of Saccharina japonica. There is a co-linear
relationship between the plastid genome of U. pinnatifida and that of three
previously sequenced large brown algal species. Phylogenetic analyses of 43 taxa
based on 23 plastid protein-coding genes grouped all plastids into a red or green
lineage. In the large brown algae branch, U. pinnatifida and S. japonica formed a
sister clade with much closer relationship to Ectocarpus siliculosus than to
Fucus vesiculosus. For the first time, the start codon ATT was identified in the
plastid genome of large brown algae, in the atpA gene of U. pinnatifida. In
addition, we found a gene-length change induced by a 3-bp repetitive DNA in ycf35
and ilvB genes of the U. pinnatifida plastid genome.
PMID- 26426801
TI - Site-adapted admixed tree species reduce drought susceptibility of mature
European beech.
AB - Some forest-related studies on possible effects of climate change conclude that
growth potential of European beech (Fagus sylvatica L.) might be impaired by the
predicted increase in future serious drought events during the growing season.
Other recent research suggests that not only multiyear increment rates but also
growth resistance and recovery of beech during, respectively, after dry years may
differ between pure and mixed stands. Thus, we combined dendrochronological
investigations and wood stable isotope measurements to further investigate the
impact of neighborhood diversity on long-term performance, short-term drought
response and soil water availability of European beech in three major geographic
regions of Germany. During the last four decades, target trees whose competitive
neighborhood consisted of co-occurring species exhibited a superior growth
performance compared to beeches in pure stands of the same investigation area.
This general pattern was also found in exceptional dry years. Although the summer
droughts of 1976 and 2003 predominantly caused stronger relative growth declines
if target trees were exposed to interspecific competition, with few exceptions
they still formed wider annual rings than beeches growing in close-by
monocultures. Within the same study region, recovery of standardized beech target
tree radial growth was consistently slower in monospecific stands than in the
neighborhood of other competitor species. These findings suggest an improved
water availability of beech in mixtures what is in line with the results of the
stable isotope analysis. Apparently, the magnitude of competitive complementarity
determines the growth response of target beech trees in mixtures. Our
investigation strongly suggest that the sensitivity of European beech to
environmental constrains depends on neighborhood identity. Therefore, the
systematic formation of mixed stands tends to be an appropriate silvicultural
measure to mitigate the effects of global warming and droughts on growth patterns
of Fagus sylvatica.
PMID- 26426802
TI - Implementation of Web-Based Respondent Driven Sampling among Men Who Have Sex
with Men in Sweden.
AB - BACKGROUND: Respondent driven sampling (RDS) was designed to study 'hidden'
populations, for which there are no available sampling frame. RDS has been shown
to recruit far into social networks of the study population and achieve unbiased
estimates when certain assumptions are fulfilled. Web-based respondent driven
sampling (WebRDS) has been implemented among MSM in Vietnam and produced a
sufficient sample of MSM. In order to see if WebRDS could work in a 'hidden'
population in a high-income setting, we performed a WebRDS among MSM in Sweden to
study a sensitive topic, sexual risk behaviour for HIV/STI and Internet use.
METHODS: A cross-sectional survey was implemented between July 11, 2012 and
January 21, 2013 by using a WebRDS software. Men, fifteen years old or above, who
reported having ever had sex with another man were included. The web-survey
explored sociodemographics, sexual risk behaviour for HIV/STI and Internet use.
RESULTS: The WebRDS process created a sample of 123 eligible respondents. The
mean age among participants was 32 years old. All respondents reported having had
unprotected anal intercourse (UAI) with at least one regular and one casual sex
partner during the last 12 months. On average participants reported having had
UAI with three casual sexual partners and in total having had seven casual sex
partners during the last 12 months. CONCLUSION: The WebRDS produced a sample of
Internet-using MSM in Sweden who all reported sexual risk behaviour for HIV/STI
during the last 12 months. It holds promise for future online studies among MSM
and a possibility to reach MSM at risk for HIV/STI with interventions or
information. Some challenges were found including short recruitment chains, and
further research need to address how to optimize WebRDS online recruitment
methods in high income settings.
PMID- 26426803
TI - Trends in Incidence of Stroke and Transition of Stroke Subtypes in Rural Tianjin
China: A Population-Based Study from 1992 to 2012.
AB - OBJECTIVES: The incidence of ischemic stroke has increased and that of
hemorrhagic stroke has decreased in urban China; however, the trends in rural
areas are unknown. We aimed to explore the secular trends in incidence and
transition of stroke subtypes among rural Chinese. METHODS: This was a population
based stroke surveillance through the Tianjin Brain Study. A total of 14,538
residents in a township of Ji County in Tianjin, China participated in the study
since 1985. We investigated the age-standardized stroke incidence (sex-specific,
type-specific, and age-specific), the annual proportion of change in the
incidence of stroke, and the proportion of intracerebral hemorrhage in the
periods 1992-1998, 1999-2005, and 2006-2012, because the neuroimaging technique
was available since 1992 in this area. RESULTS: The age-standardized incidence
per 100,000 person-years increased significantly for both intracerebral
hemorrhage (37.8 in 1992-1998, 46.5 in 1999-2005, and 76.5 in 2006-2012) and
ischemic stroke (83.9 in 1992-1998, 135.3 in 1999-2005, and 238.0 in 2006-2012).
The age-standardized incidence of first-ever stroke increased annually by 4.9%
for intracerebral hemorrhage and by 7.3% for ischemic stroke. The greatest
increase was observed in men aged 45-64 years for both stroke types (P < 0.001).
The proportion of intracerebral hemorrhage was stable overall, increased among
men aged 45-64 years, and decreased among men aged >=65 years. The average age of
intracerebral hemorrhage in men reduced by 7.5 years from 1992 to 2012.
CONCLUSION: The age-standardized incidence of main stroke subtypes increased
significantly in rural China over the past 21 years; the overall proportion of
intracerebral hemorrhage was stable, but the incidence increased significantly
among middle-aged men. These findings imply that it is crucial to control stroke
risk factors in middle-aged men for stroke prevention in future decades.
PMID- 26426804
TI - The Use of Solitaire AB Stents in Coil Embolization of Wide-Necked Cerebral
Aneurysms.
AB - BACKGROUND: The Solitaire AB stent is one of many assistant stents used for
treating wide-necked cerebral aneurysm, and has been used since 2003. However,
large sample studies on its safety and effectiveness are lacking. The objective
of this study was to evaluate the effectiveness and safety of the Solitaire AB
stent in the coil embolization of wide-necked cerebral aneurysms. METHODS:
Retrospective review of the clinical and image data of 116 patients with wide
necked cerebral aneurysms who had been enrolled at six interventional
neuroradiology centers from February 2010 to February 2014 and had been treated
by coil embolization; in total, 120 Solitaire AB stents were used. The degree of
aneurysm occlusion was examined using digital subtraction angiography (DSA)
immediately after the procedure and during follow-up, and was graded using the
modified Raymond classification. We also observed complications to evaluate the
safety and effectiveness of this therapy. RESULTS: The 120 Solitaire AB stents (4
mm * 15 mm, four stents; 4 mm * 20 mm, 16 stents; 6 mm * 20 mm, 36 stents; 6 mm *
30 mm, 64 stents) were inserted to treat 120 wide-necked cerebral aneurysms. All
stents were inserted successfully. DSA immediately post-surgery revealed 55 cases
of complete occlusion, 59 cases of neck remnant, and six cases of aneurysm
remnant. Perioperatively, there were four cases of hemorrhage and four cases of
stent thrombosis. The follow-up spanned 3-37 months; of 92 patients examined by
DSA at the 6-month follow up, 12 had disease recurrence. CONCLUSIONS: The
Solitaire AB stent is effective with a good technical success rate and short-term
effect for assisting coil embolization of wide-necked cerebral aneurysms.
PMID- 26426805
TI - The Association between Insomnia and Insomnia Treatment Side Effects on Health
Status, Work Productivity, and Healthcare Resource Use.
AB - The aims of this study were (1) to compare health outcomes (i.e., health-related
quality of life [HRQoL], productivity at work, and healthcare resource use
visits) between those with insomnia and non-insomnia controls, (2) to compare
health outcomes between those treated for insomnia and non-insomnia controls, and
(3) to assess the prevalence of side effects of insomnia medications and their
relationship with health outcomes. Data from the 2013 US (N = 75,000) and 5EU (N
= 62,000) National Health and Wellness Survey (NHWS) were used. The NHWS is a
patient-reported survey administered to a demographically representative sample
of adults. Those who met DSM-V criteria for insomnia and, separately, those
treated for insomnia were compared with equivalently sized control groups who
were identified using a propensity score matching method. Outcomes included HRQoL
(Short Form 36v2), productivity at work (Work Productivity and Activity
Impairment-General Health questionnaire), and healthcare resource use visits in
the past 6 months and were analyzed using one-way ANOVAs. Among those with
treated insomnia, those with and without side effects were compared on health
outcomes using general linear models controlling for confounding variables.
Patients with insomnia (n = 4147) and treated insomnia (n = 2860) in the 5EU
reported significantly worse HRQoL than controls (health utilities: 0.60 vs.
0.74; 0.60 vs. 0.74, respectively), greater overall work impairment (38.74% vs.
14.86%; 39.50% vs. 15.66%), and more physician visits in the past 6 months (9.10
vs. 4.08; 9.58 vs. 4.11). Similar findings were observed in the US. Among those
treated for insomnia, 13.56% and 24.55% in the US and 5EU, respectively, were non
adherent due to side effects. In the US, non-adherence was associated with
significantly worse HRQoL (health utilities: 0.60 vs. 0.64, p <.05) and greater
overall work impairment (37.71% vs. 29.08%, p <.05), among other significant
differences. These relationships were not significant in the 5EU. A significant
burden of insomnia was observed in both the US and 5EU, and the association
remained even after treatment. Non-adherence due to side effects was common and,
in the case of the US, associated with significantly poorer health outcomes.
PMID- 26426806
TI - The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like
Osteoclasts.
AB - Foreign body multinucleated giant cells (FBGCs) and osteoclasts share several
characteristics, like a common myeloid precursor cell, multinuclearity,
expression of tartrate-resistant acid phosphatase (TRAcP) and dendritic cell
specific transmembrane protein (DC-STAMP). However, there is an important
difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form
only under pathological conditions or at the surface of foreign materials, like
medical implants. Despite similarities, an important distinction between these
cell types is that osteoclasts can resorb bone, but it is unknown whether FBGCs
are capable of such an activity. To investigate this, we differentiated FBGCs and
osteoclasts in vitro from their common CD14+ monocyte precursor cells, using
different sets of cytokines. Both cell types were cultured on bovine bone slices
and analyzed for typical osteoclast features, such as bone resorption, presence
of actin rings, formation of a ruffled border, and characteristic gene expression
over time. Additionally, both cell types were cultured on a biomimetic
hydroxyapatite coating to discriminate between bone resorption and mineral
dissolution independent of organic matrix proteolysis. Both cell types
differentiated into multinucleated cells on bone, but FBGCs were larger and had a
higher number of nuclei compared to osteoclasts. FBGCs were not able to resorb
bone, yet they were able to dissolve the mineral fraction of bone at the surface.
Remarkably, FBGCs also expressed actin rings, podosome belts and sealing zones-
cytoskeletal organization that is considered to be osteoclast-specific. However,
they did not form a ruffled border. At the gene expression level, FBGCs and
osteoclasts expressed similar levels of mRNAs that are associated with the
dissolution of mineral (e.g., anion exchange protein 2 (AE2), carbonic anhydrase
2 (CAII), chloride channel 7 (CIC7), and vacuolar-type H+-ATPase (v-ATPase)), in
contrast the matrix degrading enzyme cathepsin K, which was hardly expressed by
FBGCs. Functionally, the latter cells were able to dissolve a biomimetic
hydroxyapatite coating in vitro, which was blocked by inhibiting v-ATPase enzyme
activity. These results show that FBGCs have the capacity to dissolve the mineral
phase of bone, similar to osteoclasts. However, they are not able to digest the
matrix fraction of bone, likely due to the lack of a ruffled border and cathepsin
K.
PMID- 26426810
TI - Insulin resistance and composite indices of femoral neck strength in Asians: the
fourth Korea National Health and Nutrition Examination Survey (KNHANES IV).
AB - OBJECTIVE: Fracture risk in type 2 diabetes mellitus with insulin resistance is
increased, despite relatively preserved bone mineral density (BMD). In this
study, we investigated the relationship between insulin resistance and composite
indices of femoral neck strength in Koreans. DESIGN: A population-based, cross
sectional study from the Korea National Health and Nutrition Examination Survey
PARTICIPANTS: About 1243 men and 1433 women MEASUREMENTS: Insulin resistance was
evaluated using the homoeostasis model assessment-estimated insulin resistance
(HOMA-IR) index. Femoral neck width and axis length were measured from hip dual
energy X-ray absorptiometry scans and combined with BMD, weight and height to
calculate composite indices of femoral neck strength relative to load:
compression (CSI), bending (BSI) and impact strength indices (ISI). RESULTS: HOMA
IR showed an inverse relationship with CSI, BSI and ISI in both genders before
and after adjusting for confounders (P < 0.001-0.029). CSI was more strongly
associated with HOMA-IR than BSI and/or ISI in both genders (P < 0.001-0.013).
When men were stratified according to HOMA-IR quartiles, all strength indices
decreased as the quartile increased, after adjusting for all potential
confounders (P for trend <0.001-0.001), whereas CSI and ISI did in women (P for
trend = 0.012 and 0.002, respectively). Fasting insulin levels, but not glucose
levels, were negatively associated with all strength indices regardless of
confounders (P < 0.001-0.044). CONCLUSIONS: Insulin resistance is associated with
low femoral neck strength, particularly against the compressive load. These
findings suggest a better approach to evaluate bone health in insulin-resistant
individuals.
PMID- 26426811
TI - An extended single-index multiplexed 16S rRNA sequencing for microbial community
analysis on MiSeq illumina platforms.
AB - The primary 16S rRNA sequencing protocol for microbial community analysis using
Illumina platforms includes a single-indexing approach that allows pooling of
hundreds of samples in each sequencing run. The protocol targets the V4
hypervariable region (HVR) of 16S rRNA using 150 bp paired-end (PE) sequencing.
However, the latest improvement in Illumina chemistry has increased the read
length up to 600 bp using 300 bp PE sequencing. To take advantage of the longer
read length, a dual-indexing approach was previously developed for targeting
different HVRs. However, due to simple working protocols, the single-index 150 bp
PE approach still continues to be attractive to many researchers. Here, we
described an extended single-indexing protocol for 300 bp PE illumina sequencing
that targets the V3-V4 HVRs of 16S rRNA. The new primer set led to increased read
length and alignment resolution, as well as increased richness and diversity of
resulting microbial profile compared to that obtained from150 bp PE protocol for
V4 sequencing. The beta-diversity profile also differed qualitatively and
quantitatively between the two approaches. Both primer sets had high coverage
rates and specificity to detect dominant phyla; however, their coverage rate with
regards to the rare biosphere varied. Our data further confirms that the choice
of primer is the most deterministic factor in sequencing coverage and
specificity.
PMID- 26426812
TI - Bioactive glass plus laser phototherapy as promise candidates for dentine
hypersensitivity treatment.
AB - Treatments for dentine hypersensitivity (DH) may produce positive effects, though
do not have lasting results. We investigated the reparative potential of stem
cells derived from deciduous teeth (SHEDs) in response to components delivered
from substances used in the treatment of the DH, associated or not to laser
phototherapy (LPT), to stimulate dentine formation. SHEDs were submitted to
substances delivered from a laboratorial P-rich bioactive glass [57SiO2 -26CaO
17P2 O5 (wt %)] or a commercially available desensitizer (Gluma(r) Desensitizer),
associated (or not) to LPT (InGAlP diode laser, 660 nm, 0.028 cm2 , 20 mW, 5
J/cm2 , 7 s, contact mode). Biomaterial characterization was performed by X-ray
diffraction, scanning electron microscopy and the particle size was evaluated by
dynamic light scattering. SHEDs proliferation and differentiation were analyzed
by MTT and Alizarin Red staining, respectively. The conditioned media used in
these tests were evaluated regarding their pH and the ionic concentration changes
due to ions leached from the bioactive glass (BG). BG majority presented a non
crystalline solid structure and mixed particle sizes characterized by the
agglomeration of nanoparticles. Cultures treated with BG alone or in association
to LPT showed improved cell growth in relation to Gluma(r) (p < 0.05). Gluma(r)
was cytotoxic in all tested conditions, regardless irradiated or not. BG
associated to LPT induced intense mineral matrix formation. In conclusion, BG
releases ionic dissolution products able to promote SHEDs differentiation. BG
associated to LPT improves SHEDs proliferation and differentiation in vitro, and
may be a promise therapeutic approach for the DH treatment. (c) 2015 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 107-116, 2017.
PMID- 26426814
TI - Assessment of cardiac dyssynchrony by cardiac MR: A comparison of velocity
encoding and feature tracking analysis.
AB - PURPOSE: To investigate whether cardiac magnetic resonance (cardiac MR)-based
feature tracking (FT) may be used for robust and rapid quantification of
dyssynchrony by measurement of the septal to lateral delay (SLD). MATERIALS AND
METHODS: Healthy volunteers (n = 18) and patients with mechanical dyssynchrony (n
= 17) were investigated. Velocity encoding cardiac MR (VENC) and steady-state
free precession (SSFP)-cine sequences were acquired in identical horizontal long
axis (HLA) positions using a 1.5T MR scanner. Using FT and VENC cardiac MR
software, myocardial velocity curves were calculated for the basal segment of the
septal and lateral wall. Based on the quantity of dyssynchrony, the patients were
classified into three subgroups (minimal, intermediate, extensive). SLD and
patient classification were compared and intra- as well as interobserver
variability assessed. RESULTS: VENC and FT SLD measurements showed strong
correlation (r = 0.94) and good agreement (mean 1.33 msec; limits of agreement
[LoA] -2.96 to 5.63). Dyssynchrony subclassification based on FT was identical to
VENC in 83% of the cases. While FT correctly classified all healthy subjects,
three patients with mechanical dyssynchrony were misclassified. Compared to VENC,
FT showed higher intra- and interobserver variability. VENC: intraobserver: mean
2.5 msec, LoA -17.5 to 22.5; interobserver: mean 1.5 msec, LoA -17.2 to 21.9. FT:
intraobserver: mean 2.1 msec, LoA 27.6 to 31.8; interobserver: mean 2.4 msec LoA
31.4 to 34.5. CONCLUSION: Cardiac MR-based FT analysis may be used for rapid
appraisal of left ventricle cardiac dyssynchrony from SSFP images. However, FT
results are less accurate and reproducible compared to VENC-based assessment of
SLD.
PMID- 26426813
TI - The Association of Endothelin-1 Signaling with Bone Alkaline Phosphatase
Expression and Protumorigenic Activities in Canine Osteosarcoma.
AB - BACKGROUND: Canine osteosarcoma (OS) is an aggressive sarcoma characterized by
pathologic skeletal resorption and pulmonary metastases. A number of negative
prognostic factors, including bone alkaline phosphatase, have been identified in
dogs with OS, but the underlying biologic factors responsible for such
observations have not been thoroughly investigated. Endothelin-1-mediated
signaling is active during bone repair, and is responsible for osteoblast
migration, survival, proliferation, and bone alkaline phosphatase expression.
HYPOTHESIS: The endothelin-1 signaling axis is active in canine OS cells, and
this pathway is utilized by malignant osteoblasts for promoting cellular
migration, survival, proliferation, and bone alkaline phosphatase activities.
ANIMALS: 45 dogs with appendicular OS. METHODS: The expressions of endothelin-1
and endothelin A receptor were studied in OS cell lines and in samples from
spontaneously occurring tumors. Activities mediated by endothelin-1 signaling
were investigated by characterizing responses in 3 OS cell lines. In 45 dogs with
OS, bone alkaline phosphatase concentrations were correlated with primary tumor
osteoproductivity. RESULTS: Canine OS cells express endothelin-1 and endothelin A
receptor, and this signaling axis mediates OS migration, survival, proliferation,
and bone alkaline phosphatase activities. In OS-bearing dogs, circulating bone
alkaline phosphatase activities were positively correlated with primary tumor
relative bone mineral densities. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine OS
cells express endothelin-1 and functional endothelin A receptors, with the
potential for a protumorigenic signaling loop. Increases in bone alkaline
phosphatase activity are associated with osteoblastic OS lesions, and might be an
epiphenomenon of active endothelin-1 signaling or excessive osteoproduction
within the localized bone microenvironment.
PMID- 26426816
TI - A rapid and selective synthesis of alpha,alpha-fluorohalo esters via
fluorohalogenative or difluorinative hydration of ynol ethers.
AB - A Selectfluor-mediated fluorohalogenative or difluorinative hydration of ynol
ethers is described, giving various alpha,alpha-fluorohalo esters including
alpha,alpha-bromofluoro, alpha,alpha-chlorofluoro, alpha,alpha-fluoroiodo, and
alpha,alpha-difluoro derivatives in a highly selective manner under very mild
reaction conditions. The resultant products can be applied to the facile
synthesis of alpha-monofluoro-alpha-amino acids. This reaction represents a new
advance in the trifunctionalization of alkynes.
PMID- 26426815
TI - Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect
Mechanisms: Evidence from Intervention Studies in Pigmented Mice.
AB - OBJECTIVE: Daily application of far-red light from the onset of diabetes
mitigated diabetes-induced abnormalities in retinas of albino rats. Here, we test
the hypothesis that photobiomodulation (PBM) is effective in diabetic, pigmented
mice, even when delayed until weeks after onset of diabetes. Direct and indirect
effects of PBM on the retina also were studied. METHODS: Diabetes was induced in
C57Bl/6J mice using streptozotocin. Some diabetics were exposed to PBM therapy (4
min/day; 670 nm) daily. In one study, mice were diabetic for 4 weeks before
initiation of PBM for an additional 10 weeks. Retinal oxidative stress,
inflammation, and retinal function were measured. In some mice, heads were
covered with a lead shield during PBM to prevent direct illumination of the eye,
or animals were treated with an inhibitor of heme oxygenase-1. In a second study,
PBM was initiated immediately after onset of diabetes, and administered daily for
2 months. These mice were examined using manganese-enhanced MRI to assess effects
of PBM on transretinal calcium channel function in vivo. RESULTS: PBM
intervention improved diabetes-induced changes in superoxide generation,
leukostasis, expression of ICAM-1, and visual performance. PBM acted in part
remotely from the retina because the beneficial effects were achieved even with
the head shielded from the light therapy, and because leukocyte-mediated
cytotoxicity of retinal endothelial cells was less in diabetics treated with PBM.
SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but
significantly exacerbated leukostasis. In study 2, PBM largely mitigated diabetes
induced retinal calcium channel dysfunction in all retinal layers. CONCLUSIONS:
PBM induces retinal protection against abnormalities induced by diabetes in
pigmented animals, and even as an intervention. Beneficial effects on the retina
likely are mediated by both direct and indirect mechanisms. PBM is a novel non
pharmacologic treatment strategy to inhibit early changes of diabetic
retinopathy.
PMID- 26426817
TI - Ultrathin unsedated transnasal gastroscopy in monitoring eosinophilic
esophagitis.
AB - BACKGROUND: Ultrathin unsedated transnasal gastroscopy (UTEG) has a number of
advantages applicable to eosinophilic esophagitis (EoE) and has not been
evaluated for this condition. AIM: The aim of the study is to determine the
feasibility of UTEG in patients with EoE and the acceptability of histological
specimens obtained at biopsy. METHOD: All patients with a diagnosis of EoE
presenting to the outpatients department of two hospitals (Box Hill Hospital and
The Alfred Hospital, Melbourne Australia) were asked to participate in the study.
UTEG was performed on consenting individuals. Feasibility was determined by the
success of nasal intubaton, patient perception according to post procedural
survey, and adequacy of esophageal biopsies was assessed. RESULTS: Ninety-six
consecutive patients with EoE were offered UTEG, and 24 agreed to participate in
the study. Seventy-four UTEGs were performed over a period of 26 months
(September 2012 to December 2014). Nineteen patients had repeat procedures.
Successful nasal intubation occurred in 97% (72 of 74 procedures), and 21 of 24
(86%) described high satisfaction with the procedure and minimal discomfort, and
would choose UTEG for future procedures. Mean duration was 5 min. Adverse events
of epistaxis (three cases) and vomiting of liquid contents during the procedure
(two cases) were recorded, cardiorespiratory parameters remaining normal in all
patients. All completed procedures produced adequate histological samples.
CONCLUSION: In those who decide to undergo UTEG, it is a safe and well-tolerated
procedure.
PMID- 26426819
TI - Impaired Visual Acuity and Spectacle Ownership of Urban Migrant Children in
Eastern China.
PMID- 26426818
TI - Exogenous attention facilitates location transfer of perceptual learning.
AB - Perceptual skills can be improved through practice on a perceptual task, even in
adulthood. Visual perceptual learning is known to be mostly specific to the
trained retinal location, which is considered as evidence of neural plasticity in
retinotopic early visual cortex. Recent findings demonstrate that transfer of
learning to untrained locations can occur under some specific training
procedures. Here, we evaluated whether exogenous attention facilitates transfer
of perceptual learning to untrained locations, both adjacent to the trained
locations (Experiment 1) and distant from them (Experiment 2). The results reveal
that attention facilitates transfer of perceptual learning to untrained locations
in both experiments, and that this transfer occurs both within and across visual
hemifields. These findings show that training with exogenous attention is a
powerful regime that is able to overcome the major limitation of location
specificity.
PMID- 26426822
TI - Interactions between Flavins and Quadruplex Nucleic Acids.
AB - Quadruplex nucleic acids are widespread in genomes. They influence processes such
as transcription, translation, replication, recombination, and the regulation of
gene expression. Several synthetic ligands have been demonstrated to target
quadruplex nucleic acids. However, only very few metabolites have been reported
to interact with quadruplexes. In principle, an intracellular metabolite that
selectively binds to four-stranded sequences could modulate quadruplex formation,
stability, and thus functions in a riboswitch (or deoxyriboswitch) manner. Here
we report quadruplex interactions with flavin derivatives such as FMN and FAD.
The affinities were highest with parallel quadruplexes, with low (14-20 MUm)
dissociation constants. Taking into account combined intracellular flavin
concentrations of 243 MUm in E. coli, the observed interactions in principle open
up the possibility of flavin levels affecting gene expression and other processes
by modulating quadruplex formation.
PMID- 26426823
TI - Antibody-Modified Reduced Graphene Oxide Films with Extreme Sensitivity to
Circulating Tumor Cells.
AB - An antibody-modified reduced graphene oxide (rGO) film with unexpected -extreme
sensitivity to circulating tumor cells (CTCs) is reported. The antibody--modified
rGO films efficiently capture CTCs from billions of blood cells and minimize the
background of white blood cells, without complex microfluidic operations.
PMID- 26426824
TI - Configurable lipid membrane gradients quantify diffusion, phase separations and
binding densities.
AB - Single-experiment analysis of phospholipid compositional gradients reveals
diffusion coefficients, phase separation parameters, and binding densities as a
function of localized lipid mixture. Compositional gradients are formed by
directed self assembly where rapid-prototyping techniques (i.e., additive
manufacturing or laser-cutting) prescribe lipid geometries that self-spread, heal
and mix by diffusion.
PMID- 26426825
TI - Chiral modification of platinum: ab initio study of the effect of hydrogen
coadsorption on stability and geometry of adsorbed cinchona alkaloids.
AB - The cinchona alkaloids cinchonidine and cinchonine belong to the most efficient
chiral modifiers for the noble metal-catalyzed enantioselective hydrogenation of
C=O and C=C bonds. Under reaction conditions these modifiers are coadsorbed on
the noble metal surface with hydrogen. Using density functional theory, we
studied the effect of coadsorbed hydrogen on the adsorption mode of cinchonidine
and cinchonine on a Pt(111) surface at different hydrogen coverages. The
theoretical study indicates that the presence of coadsorbed hydrogen affects both
the adsorption geometry as well as the stability of the adsorbed cinchona
alkaloids. At all hydrogen coverages the cinchona alkaloids are found to be
adsorbed via anchoring of the quinoline moiety. In the absence of hydrogen as
well as at low hydrogen coverage the quinoline moiety adsorbs nearly parallel to
the surface, whereas at higher hydrogen coverage it becomes tilted. Higher
hydrogen coverage as well as partial hydrogenation of the quinoline part of the
cinchona alkaloid and hydrogen transfer to the C[double bond, length as m-dash]C
double bond at 10, 11 position of the quinuclidine moiety destabilize the
adsorbed cinchona alkaloid, whereas hydrogen transfer to the nitrogen atom of the
quinoline and the quinuclidine moiety stabilizes the adsorbed molecule. The
stability as well as the adsorption geometry of the cinchona alkaloids are
affected by the coadsorbed hydrogen and are proposed to influence the efficiency
of the enantiodifferentiating ability of the chirally modified platinum surface.
PMID- 26426827
TI - Copper- and Silver-Catalyzed Diastereo- and Enantioselective Conjugate Addition
Reaction of 1-Pyrroline Esters to Nitroalkenes: Diastereoselectivity Switch by
Chiral Metal Complexes.
AB - syn-Diastereoselective conjugate addition of 1-pyrroline esters to nitroalkenes
in good yields with an excellent enantioselectivity by using CuOAc/Me-FcPHOX
catalyst in the presence of pyridine. In contrast, AgOAc/tBu-ThioClickFerrophos
catalyzed the anti diastereoselective conjugate addition with a high
enantioselectivity without additional base. Thus, the preparation of chiral 1
pyrroline derivatives bearing diverse stereochemistry could be achieved. The
diastereoselective reduction of the imine group in the conjugate adduct could
afford the 2,5-cis-proline ester derivative.
PMID- 26426826
TI - Genetics of murine craniofacial morphology: diallel analysis of the eight
founders of the Collaborative Cross.
AB - Using eight inbred founder strains of the mouse Collaborative Cross (CC) project
and their reciprocal F1 hybrids, we quantified variation in craniofacial
morphology across mouse strains, explored genetic contributions to craniofacial
variation that distinguish the founder strains, and tested whether specific or
summary measures of craniofacial shape display stronger additive genetic
contributions. This study thus provides critical information about phenotypic
diversity among CC founder strains and about the genetic contributions to this
phenotypic diversity, which is relevant to understanding the basis of variation
in standard laboratory strains and natural populations. Craniofacial shape was
quantified as a series of size-adjusted linear dimensions (RDs) and by principal
components (PC) analysis of morphological landmarks captured from computed
tomography images from 62 of the 64 reciprocal crosses of the CC founder strains.
We first identified aspects of skull morphology that vary between these
phenotypically 'normal' founder strains and that are defining characteristics of
these strains. We estimated the contributions of additive and various non
additive genetic factors to phenotypic variation using diallel analyses of a
subset of these strongly differing RDs and the first eight PCs of skull shape
variation. We find little difference in the genetic contributions to RD measures
and PC scores, suggesting fundamental similarities in the magnitude of genetic
contributions to both specific and summary measures of craniofacial phenotypes.
Our results indicate that there are stronger additive genetic effects associated
with defining phenotypic characteristics of specific founder strains, suggesting
these distinguishing measures are good candidates for use in genotype-phenotype
association studies of CC mice. Our results add significantly to understanding of
genotype-phenotype associations in the skull, which serve as a foundation for
modeling the origins of medically and evolutionarily relevant variation.
PMID- 26426828
TI - Thyroid Cancer and Nonsteroidal Anti-Inflammatory Drug Use: A Pooled Analysis of
Patients Older Than 40 Years of Age.
AB - BACKGROUND: Cyclooxygenase (COX-2) has been associated with tumor growth and
metastasis in several cancers, including thyroid cancer. For this reason, several
investigators have studied COX-2 inhibitors in preclinical models of thyroid
cancer and found antineoplastic effects. Thus, the primary aim of this study was
to assess if the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is
associated with a reduced incidence of thyroid cancer. A second aim of the study
was to determine additional risk or protective factors for thyroid cancer.
METHODS: Three large prospective population-based studies (the NIH-AARP Diet and
Health Study; the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial;
and the U.S. Radiologic Technologists Study) were pooled to investigate the
association between self-reported frequency of aspirin and nonaspirin NSAID use
one year prior to baseline (no use, <= 2/week, >2-6/week, and >= 7/week) and
subsequent risk of thyroid cancer. A Cox regression proportional hazard model was
used to estimate aggregated hazard ratios (HR) adjusted for cohort, sex,
race/ethnicity, weight, smoking status, and alcohol intake. RESULTS: There were
388,577 participants in the pooled cohort, with 481 cases of thyroid cancer. No
significant risk reduction was observed with regular use of nonaspirin NSAIDs (HR
= 1.14 [confidence interval (CI) 0.84-1.55]), and/or regular use of aspirin (HR =
1.06 [CI 0.82-1.39]). The multivariate regression analysis confirmed as
previously reported in the literature that female sex, obesity class I (body mass
index [BMI] = 30-34.99 kg/m(2)), and obesity class II (BMI = 35-35.99 kg/m(2))
were independently associated with an increased thyroid cancer risk. Current
smoking status and moderate and excessive alcohol use were also confirmed as
independent risk factors associated with a reduced thyroid cancer risk.
CONCLUSIONS: Neither nonaspirin NSAIDs nor aspirin use is associated with a
reduced risk of thyroid cancer. Women and obesity are associated with an
increased risk of thyroid cancer, whereas smoking and alcohol use are associated
with decreased risk of thyroid cancer.
PMID- 26426829
TI - A Chimeric Cetuximab-Functionalized Corona as a Potent Delivery System for
Microtubule-Destabilizing Nanocomplexes to Hepatocellular Carcinoma Cells: A
Focus on EGFR and Tubulin Intracellular Dynamics.
AB - In this study, we have developed microtubule destabilizing agents combretastatin
A4 (CA4) or 2-methoxyestradiol (2ME) encapsulated poly(d,l-lactide-co-glycolide)
b-poly(ethylene glycol) (PLGA-b-PEG) nanocomplexes for targeted delivery to human
hepatocellular carcinoma (HCC) cells. An epidermal growth factor receptor (EGFR)
is known to be overexpressed in HCC cells. Therefore, the targeting moiety
cetuximab (Cet), an anti-EGFR chimeric monoclonal antibody, is functionalized on
the surface of these diblock copolymeric coronas. Cetuximab is associated with
the extracellular domain of the EGFR; therefore, the uptake of the cetuximab
conjugated nanocomplexes occurred efficiently in EGFR overexpressing HCC cells
indicating potent internalization of the complex. The cetuximab targeted-PLGA-b
PEG nanocomplexes encapsulating CA4 or 2ME strongly inhibited phospho-EGFR
expression, depolymerized microtubules, produced spindle abnormalities, stalled
mitosis, and induced apoptosis in Huh7 cells compared to the free drugs, CA4 or
2ME. Further, the combinatorial strategy of targeted nanocomplexes, Cet-PLGA-b
PEG-CA4 NP and Cet-PLGA-b-PEG-2ME NP, significantly reduced the migration of Huh7
cells, and markedly enhanced the anticancer effects of the microtubule-targeted
drugs in Huh7 cells compared to the free drugs, CA4 or 2ME. The results indicated
that EGFR receptor-mediated internalization via cetuximab facilitated enhanced
uptake of the nanocomplexes leading to potent anticancer efficacy in Huh7 cells.
Cetuximab-functionalized PLGA-b-PEG nanocomplexes possess a strong potential for
the targeted delivery of CA4 or 2ME in EGFR overexpressed HCC cells, and the
strategy may be useful for selectively targeting microtubules in these cells.
PMID- 26426830
TI - Antimicrobials at the End of Life: An Opportunity to Improve Palliative Care and
Infection Management.
PMID- 26426831
TI - Serum lipid profile changes after successful treatment with electroconvulsive
therapy in major depression: A prospective pilot trial.
AB - BACKGROUND: Cholesterol is reduced in depressed patients, however, these patients
have a higher risk for cardiovascular diseases. Electroconvulsive therapy (ECT)
is a highly effective treatment option for specific forms of depression. Like for
other non-pharmacological therapies targeting depression such as psychotherapy or
sleep deprivation, there is a lack of evidence about the effects on peripheral
lipid parameters. Our objective was to study the impact of ECT as a non
pharmacological treatment on the peripheral lipid pattern in depressive patients.
METHOD: Peripheral lipid profile composition before and after a course of ECT was
analysed in 27 non-fasting inpatients at a university psychiatric hospital with
DSM-IV major depressive episode. For the impact of ECT treatment on each lipid
parameter a multivariate repeated measurement regression analysis was performed
and computed separately for every dependent variable. RESULTS: Total Cholesterol
and the cholesterol subtypes HDL and LDL were increased after the treatment
compared to baseline. Apolipoprotein A1 was also increased after ECT, whereas
apolipoprotein B was not. Indices for the prediction of cardiovascular diseases
were unchanged after successful treatment by ECT. The reduction of depressive
psychopathology negatively correlated with increases of HDL cholesterol and
apolipoprotein A1. LIMITATIONS: Subjects received several antidepressants and
other psychotropic medication before and during the ECT. CONCLUSIONS: In our
preliminary pilot study ECT as a non-pharmacological, effective treatment of
depression led to distinct effects on the peripheral lipid pattern.
PMID- 26426832
TI - Survival and risk factors related to death in outpatients with cirrhosis treated
in a clinic in Southern Brazil.
AB - INTRODUCTION: Cirrhosis represents a public health issue that generally evolves
and presents serious complications. OBJECTIVES: To assess the outcomes of
outpatients with cirrhosis. PATIENTS AND METHODS: We used a retrospective
outpatient-based cohort, assessing 527 patients with cirrhosis. Demographic,
clinical, and laboratory variables were analyzed, as well as the risk factors
related to death, using the Cox proportional-hazard regression model. The Kaplan
Meier method was used to analyze survival rates. RESULTS: Patients had a mean age
of 52.9+/-9.7 years and were more frequently men (59%), presenting Child-Turcotte
Pugh B or C in 43% of the cases in addition to a mean Model for End-Stage Liver
Disease score of 12.0+/-4.1. The predominant etiology of liver disease was the
hepatitis C virus. The most frequent complications during follow-up were ascites
(34%), hepatic encephalopathy (17%), and hepatocellular carcinoma (17%). The
survival rate at years 5 and 10 was 73 and 57%, respectively. The main risk
factors that were related to death were, in a multivariate analysis, hepatitis C
virus etiology, presence of hepatocellular carcinoma, and serum levels of
albumin. CONCLUSION: Patients with cirrhosis monitored on an outpatient basis,
despite showing a reasonable survival rate, have a worse prognosis when the
etiology of liver disease is related to hepatitis C virus and when they have
hepatocellular carcinoma or hypoalbuminemia.
PMID- 26426833
TI - Gallstones are associated with hidradenitis suppurativa: a population-based and
hospital-based cross-sectional study from Denmark.
AB - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory
dermatological disease that was recently linked to the metabolic syndrome (MetS).
MetS has been associated with gallstones, and nonalcoholic fatty liver has been
suggested to be the hepatic expression of MetS. OBJECTIVE: The objective of the
study was to investigate whether there was an association of HS with gallstones
as well as with hepatic dysfunction. PATIENTS AND METHODS: This was a cross
sectional study comparing a hospital-based HS group, a population-based HS group,
and controls for self-reported gallstone and blood sample verified hepatic
dysfunction. Blood samples were analyzed for alanine transaminase, bilirubin,
alkaline phosphatase, albumin, thrombocytes, and the international normalized
ratio. RESULTS: A total of 32 hospital HS patients, 430 population-based HS
patients, and 20 780 non-HS controls were identified. The age-sex-smoking
adjusted analysis of gallstones revealed a significant OR of 1.72 (95% CI 1.23
2.42, P=0.0191) and a borderline significant OR of 3.28 (95% CI 1.24-8.74,
P=0.0516) for the population HS group and hospital HS group versus controls,
respectively. Furthermore, no clinically significant evidence was found with
regard to hepatic dysfunction. CONCLUSION: This study demonstrates an association
of HS with gallstones, but not with hepatic dysfunction. The association with
gallstones may be partly explained by the comorbidity of hypertriglyceridemia and
obesity as a part of MetS.
PMID- 26426835
TI - Adalimumab as a second-line biological therapy in children with refractory
ulcerative colitis.
AB - AIM: The role of adalimumab in medically refractory ulcerative colitis (UC) in
children remains to be defined. The aim of this study was to describe 11 cases of
paediatric patients who received adalimumab as a second-line anti-TNF-alpha
treatment for paediatric UC. METHODS: A retrospective review of all patients with
UC who received adalimumab between April 2008 and October 2013 at our hospital
was conducted. Clinical efficacy and safety were assessed. RESULTS: Eleven
patients (three boys, eight girls) with a median age of 13.8 years (5.7-16.6
years) were included. All patients had been previously treated with infliximab.
Six patients achieved and maintained clinical remission, with a median duration
of treatment of 25 months. One patient was successfully weaned off adalimumab
after 26 months of therapy. Treatment was unsuccessful in four out of 11 patients
(36%) who underwent colectomy 4-13 months (median 7 months) from the first
adalimumab dose. The remaining patient developed extensive rash and was switched
to alternative therapy. CONCLUSION: In this case series, our experience shows
that there is a role for adalimumab as a combination therapy in a subgroup of
children with refractory UC.
PMID- 26426836
TI - A multicenter randomized comparison between high-definition white light endoscopy
and narrow band imaging for detection of gastric lesions.
AB - OBJECTIVE: Narrow band imaging (NBI) is generally considered to be useful for
lesion characterization, but not enhanced detection of gastric lesions, because
of the dark endoscopic view. We tested whether the new generation of NBI (190-NBI
or 290-NBI), which is twice as bright as the previous version, would improve
detection of premalignant gastric lesions compared with high-definition white
light endoscopy (HD-WLE). PATIENTS AND METHODS: This was a multicenter
prospective randomized study involving five tertiary institutions in the Asia
Pacific region. A total of 579 patients aged older than 50 years who underwent
diagnostic upper gastrointestinal endoscopy were randomized to either HD-WLE or
NBI. The outcome measurements were detection of intestinal metaplasia (IM), focal
gastric lesions, and gastric cancers. RESULTS: Focal gastric lesions were
detected in 83/286 (29%) and 119/293 patients (40.6%) by HD-WLE and by NBI,
respectively (P=0.003). IM was detected in 22/286 patients (7.7%) by HD-WLE and
in 52/293 patients (17.7%) by NBI (P<0.001). Gastric cancer were found in 7/286
(2.4%) and 3/293 patients (1%) in HD-WLE and NBI groups, respectively (P=0.189).
CONCLUSION: NBI increased the detection rate of IM compared with HD-WLE.
PMID- 26426834
TI - Diagnosis of bile acid diarrhoea by fasting and postprandial measurements of
fibroblast growth factor 19.
AB - BACKGROUND: A deficiency in the ileal hormone fibroblast growth factor 19 (FGF19)
has been described in patients with bile acid diarrhoea (BAD), but fasting FGF19
levels have insufficient diagnostic power. We assess whether single postprandial
sampling of FGF19 has greater discriminative value than fasting FGF19 for
detection of BAD and we evaluate the reproducibility of fasting FGF19. MATERIALS
AND METHODS: Twenty-six patients consecutively referred to Se homocholic acid
retention test (SeHCAT) were included. Serum FGF19 was measured after an
overnight fast and again 1 h postprandially and again in the fasting state 1 week
later. RESULTS: Nine of 26 patients had SeHCAT less than 10% and fasting FGF19
was lower [median 62 pg/ml, interquartile range (IQR): 47-67] than in the 17
diarrhoea controls with SeHCAT at least 10% (median 103 pg/ml, IQR: 77-135,
P=0.006). Postprandial FGF19 in BAD patients (61 pg/ml, IQR: 48-69) was similar
to fasting values (P=0.59) and increased insignificantly in diarrhoea controls
(137 pg/ml, IQR: 88-182; P=0.25). The difference in postprandial FGF19 between
patients with BAD and diarrhoea controls was highly significant (P<0.001).
CONCLUSION: The difference in serum FGF19 between groups of patients with BAD and
diarrhoea controls is amplified postprandially. Within each group, the difference
between fasting and postprandial FGF19 was not statistically significant. Further
investigations are warranted on stimulated FGF19 response to elucidate its role
in BAD.
PMID- 26426837
TI - Self-expandable metal stent placement for malignant duodenal obstruction distal
to the bulb.
AB - OBJECTIVE: Self-expandable metal stents (SEMS) are widely used for the palliative
management of malignant proximal gastroduodenal obstruction because of its low
morbidity and mortality rates compared with surgical bypass. However, stent
placement for duodenal obstruction beyond the first part of the duodenum is
considered technically difficult and is not routinely performed. We report our
experience with SEMS placement for these patients. METHODS: Between 2006 and
2015, 51 patients with unresectable or metastatic malignancy underwent SEMS
placements under combined endoscopic and fluoroscopic guidance. Eighteen patients
had intestinal obstruction distal to the duodenal bulb. Their demographics,
technical and clinical outcomes, periprocedural morbidity and mortality, length
of hospital stay, further interventions and overall survival were analysed.
RESULTS: Out of the 18 cases, nine cases of intestinal obstruction were due to
primary malignancy of the pancreas, three due to gastric malignancy, three from
other locoregional cancers and three were the result of metastases. In 12
patients, the obstruction involved the second part (D2), in four the third part
(D3) and in two the fourth part (D4) of the duodenum. A front-facing therapeutic
gastroscope was used to visualize the duodenum before the stricture was crossed
under direct vision and fluoroscopic guidance, with a catheter and guidewire, and
a through-the-scope SEMS deployed using an 'over-the-wire' technique. Technical
success rate was 89%. The mean gastric outlet obstruction scores improved from
0.63 to 2.57 (P<0.0001). Four patients died within 30 days of the procedure,
although none of the deaths were procedure related. The median length of
postprocedural hospital stay was 4 days and the median overall survival was 58
days.
PMID- 26426838
TI - FoxP3-positive T cell lymphoma arising in non-HTLV1 carrier: clinicopathological
analysis of 11 cases of PTCL-NOS and 2 cases of mycosis fungoides.
AB - AIMS: Forkhead box protein 3-positive (FoxP3(+) ) T cell lymphoma, in the absence
of human T cell lymphotrophic virus type 1 (HTLV-1) infection, is rare and its
clinicopathological characteristics still remain unclear. The aim of this study
was to elucidate its characteristics. METHODS AND RESULTS: We describe here 11
cases of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) and two
cases of mycosis fingoides (MF) which were positive for FoxP3. The median age of
the 11 PTCL-NOS cases was 65 years (range: 48-80 years), and all the patients
were male. Eight patients (80%) showed stages III/IV disease, and six (60%) were
categorized as high-intermediate/high-risk groups according to the International
Prognostic Index. Two cases of MF were 57- and 59-year-old males. Both cases were
categorized as stage IA, according to International Society for Cutaneous
Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC)
classification. Immunohistochemically, all the cases were negative for cytotoxic
molecule marker, and nine (75%) were alphabeta T cell type. Scattered Epstein
Barr virus (EBV)-infected cells were detected in four cases of PTCL-NOS, implying
the reactivation of EBV caused by the immunodeficient status of the patients.
CONCLUSIONS: FoxP3(+) PTCL-NOS constitute a minor phenotypical subtype with poor
prognosis and EBV reactivation in some. Conversely, two cases of MF showed an
indolent clinical course which was different from previously reported cutaneous T
cell lymphoma (CTCL) cases.
PMID- 26426839
TI - Dust in the wind: How climate variables and volcanic dust affect rates of tooth
wear in Central American howling monkeys.
AB - OBJECTIVES: Two factors have been considered important contributors to tooth
wear: dietary abrasives in plant foods themselves and mineral particles adhering
to ingested food. Each factor limits the functional life of teeth. Cross
population studies of wear rates in a single species living in different habitats
may point to the relative contributions of each factor. MATERIALS AND METHODS: We
examine macroscopic dental wear in populations of Alouatta palliata (Gray, 1849)
from Costa Rica (115 specimens), Panama (19), and Nicaragua (56). The sites
differ in mean annual precipitation, with the Panamanian sites receiving more
than twice the precipitation of those in Costa Rica or Nicaragua (~3,500 mm vs.
~1,500 mm). Additionally, many of the Nicaraguan specimens were collected
downwind of active plinian volcanoes. Molar wear is expressed as the ratio of
exposed dentin area to tooth area; premolar wear was scored using a ranking
system. RESULTS: Despite substantial variation in environmental variables and the
added presence of ash in some environments, molar wear rates do not differ
significantly among the populations. Premolar wear, however, is greater in
individuals collected downwind from active volcanoes compared with those living
in environments that did not experience ash-fall. DISCUSSION: Volcanic ash seems
to be an important contributor to anterior tooth wear but less so in molar wear.
That wear is not found uniformly across the tooth row may be related to
malformation in the premolars due to fluorosis. A surge of fluoride accompanying
the volcanic ash may differentially affect the premolars as the molars fully
mineralize early in the life of Alouatta.
PMID- 26426840
TI - Increasing the thermopower of crown-ether-bridged anthraquinones.
AB - We investigate strategies for increasing the thermopower of crown-ether-bridged
anthraquinones. The novel design feature of these molecules is the presence of
either () crown-ether or () diaza-crown-ether bridges attached to the side of the
current-carrying anthraquinone wire. The crown-ether side groups selectively bind
alkali-metal cations and when combined with TCNE or TTF dopants, provide a large
phase-space for optimising thermoelectric properties. We find that the optimum
combination of cations and dopants depends on the temperature range of interest.
The thermopowers of both and are negative and at room temperature are optimised
by binding with TTF alone, achieving thermpowers of -600 MUV K(-1) and -285 MUV
K(-1) respectively. At much lower temperatures, which are relevant to cascade
coolers, we find that for , a combination of TTF and Na(+) yields a maximum
thermopower of -710 MUV K(-1) at 70 K, whereas a combination of TTF and Li(+)
yields a maximum thermopower of -600 MUV K(-1) at 90 K. For , we find that TTF
doping yields a maximum thermopower of -800 MUV K(-1) at 90 K, whereas at 50 K,
the largest thermopower (of -600 MUV K(-1)) is obtain by a combination TTF and
K(+) doping. At room temperature, we obtain power factors of 73 MUW m(-1) K(-2)
for (in combination with TTF and Na(+)) and 90 MUW m(-1) K(-2) for (with TTF).
These are higher or comparable with reported power factors of other organic
materials.
PMID- 26426842
TI - The structures of CyMe4-BTBP complexes of americium(iii) and europium(iii) in
solvents used in solvent extraction, explaining their separation properties.
AB - Separation of trivalent actinoid (An(iii)) and lanthanoid (Ln(iii)) ions is
extremely challenging due to their similar ionic radii and chemical properties.
Poly-aromatic nitrogen compounds acting as tetradentate chelating ligands to the
metal ions in the extraction, have the ability to sufficiently separate An(iii)
from Ln(iii). One of these compounds, 6,6'-bis(5,5,8,8-tetramethyl-5,6,7,8
tetrahydro-benzol[1,2,4]triazin-3-yl)[2,2]bipyridine, CyMe4-BTBP, has proven to
be resistant towards acidic environments and strong radiation from radioactive
decomposition. EXAFS studies of the dicomplexes of CyMe4-BTBP with americium(iii)
and europium(iii) in nitrobenzene, cyclohexanone, 1-hexanol, 1-octanol and
malonamide (DMDOHEMA) in 1-octanol have been carried out to get a deeper
understanding of the parameters responsible for the separation. The predominating
complexes independent of solvent used are [Am(CyMe4-BTBP)2(NO3)](2+) and
[Eu(CyMe4-BTBP)2](3+), respectively, which are present as outer-sphere ion-pairs
with nitrate ions in the studied solvents with low relative permittivity. The
presence of a nitrate ion in the first coordination sphere of the americium(iii)
complex compensates the charge density of the complex considerably in comparison
when only outer-sphere ion-pairs are formed as for the [Eu(CyMe4-BTBP)2](3+)
complex. The stability and solubility of a complex in a solvent with low relative
permittivity increase with decreasing charge density. The [Am(CyMe4
BTBP)2(NO3)](2+) complex will therefore be increasingly soluble and stabilized
over the [Eu(CyMe4-BTBP)2](3+) complex in solvents with decreasing relative
permittivity of the solvent. The separation of americium(iii) from europium(iii)
with CyMe4-BTBP as extraction agent will increase with decreasing relative
permittivity of the solvent, and thereby also with decreasing solubility of CyMe4
BTBP. The choice of solvent is therefore a balance of a high separation factor
and sufficient solubility of the CyMe4-BTBP ligand.
PMID- 26426848
TI - Synthesis and Evaluation of 5,5'-Bitetralone-Based Chiral Phosphoric Acids.
AB - A new type of phosphoric acid bearing a 5,5'-bitetralone scaffold was synthesized
from BINOL and was shown to be a highly effective catalyst as illustrated in the
asymmetric transfer hydrogenation of 2-phenylquinoline and the Friedel-Crafts
reaction of 2,2,2-trifluoroacetophenone.
PMID- 26426849
TI - Water Selective Imaging and bSSFP Banding Artifact Correction in Humans and Small
Animals at 3T and 7T, Respectively.
AB - INTRODUCTION: The purpose of this paper is to develop an easy method to generate
both fat signal and banding artifact free 3D balanced Steady State Free
Precession (bSSFP) images at high magnetic field. METHODS: In order to suppress
fat signal and bSSFP banding artifacts, two or four images were acquired with the
excitation frequency of the water-selective binomial radiofrequency pulse set On
Resonance or shifted by a maximum of 3/4TR. Mice and human volunteers were imaged
at 7 T and 3 T, respectively to perform whole-body and musculoskeletal imaging.
"Sum-Of-Square" reconstruction was performed and combined or not with parallel
imaging. RESULTS: The frequency selectivity of 1-2-3-2-1 or 1-3-3-1 binomial
pulses was preserved after (3/4TR) frequency shifting. Consequently, whole body
small animal 3D imaging was performed at 7 T and enabled visualization of small
structures within adipose tissue like lymph nodes. In parallel, this method
allowed 3D musculoskeletal imaging in humans with high spatial resolution at 3 T.
The combination with parallel imaging allowed the acquisition of knee images with
~500 MUm resolution images in less than 2 min. In addition, ankles, full head
coverage and legs of volunteers were imaged, demonstrating the possible
application of the method also for large FOV. CONCLUSION: In conclusion, this
robust method can be applied in small animals and humans at high magnetic fields.
The high SNR and tissue contrast obtained in short acquisition times allows to
prescribe bSSFP sequence for several preclinical and clinical applications.
PMID- 26426851
TI - Glomerular filtration rate measured by iohexol clearance: A comparison of venous
samples and capillary blood spots.
AB - BACKGROUND: Glomerular filtration rate (GFR) measured by iohexol clearance using
venous samples is widely used. Capillary sampling on filter paper is easier to
perform, may be less painful and spares the blood volume. The purpose of the
study was to validate a blood spot method for measuring GFR in children aged 6
years or younger suffering from chronic kidney disease (CKD). METHODS: We
examined 32 children with CKD, median age (range) 3.0 (0.3-6.2) years. Seven
venous samples (10, 30/60, 120, 180, 210, 240, 300 min) were collected and GFR
based on all samples was calculated for reference. Following injection of
iohexol, blood spots were collected at 120, 180, 210 and 240 min and compared to
the reference iohexol clearance. RESULTS: Median (range) reference GFR was 65 (6
122) mL/min/1.73 m(2). The 2, 3 and 4-point blood spot GFR were highly correlated
to the reference GFR (r = 0.947, 0.945, 0.937). The mean relative bias between 2
point blood spot and reference GFR was 7.2%, and only 2.3% in the patients with
reference GFR < 60 mL/min/1.73 m(2). The diagnostic accuracy for 2-point blood
spot was: 87.5% and 96.9% within +/- 15% (P15) and +/- 30% (P30) of the reference
GFR respectively. In patients with GFR < 60 mL/min/1.73 m(2), both P15 and P30
were 100%. CONCLUSIONS: GFR calculation based on blood spot iohexol measurement
is an alternative method to traditional venous iohexol measurement in children.
Our study demonstrates strong agreement between the blood spot and the venous GFR
with acceptable bias, precision and diagnostic accuracy, especially in patients
with GFR < 60 mL/min/1.73 m(2).
PMID- 26426850
TI - Evaluation of a newly developed quantitative heart-type fatty acid binding
protein assay based on fluorescence immunochromatography using specific
monoclonal antibodies.
AB - OBJECTIVES: To develop a rapid, sensitive and specific assay for quantification
of serum heart-type fatty acid binding protein (H-FABP) based on
immunofluorescence of specific monoclonal antibodies. DESIGN AND METHODS: We
generated novel H-FABP-directed monoclonal antibodies by cloning of spleen cells
of mice immunized with H-FABP. Epitopes were mapped and antigen affinity was
assessed by surface plasmon resonance (SPR). The H-FABP specific monoclonal
antibodies were coupled to fluorescent beads and sprayed onto a nitrocellulose
membrane facilitating quantification of H-FABP by immunofluorescence. Reagent
cross-reactivity, interference resistance, accuracy and sensitivity were
examined. A total of 103 clinical samples were used to compare the sensitivity
and specificity of the new assay to a commercially available Randox kit. RESULTS:
This new assay could be finished within 15 min, with sensitivity reaching 1
ng/ml. In a trial of 103 clinical serum samples, the new testing kit results were
highly correlated with those from the Randox kit (R(2) = 0.9707). Using the
Randox kit as the reference kit, the sensitivity of the new assay was 98.25%, and
specificity was 100%. CONCLUSIONS: An immunofluorescence-based H-FABP assay
employing novel monoclonal antibodies could rapidly, specifically and sensitively
detect H-FABP in serum samples, providing an effective method for rapid clinical
assessment of H-FABP index in the clinic.
PMID- 26426852
TI - Impact of incorrect filling of citrate blood sampling tubes on
thromboelastometry.
AB - BACKGROUND: ROTEM((r)) test results can be affected by the citrate to blood ratio
in the tested sample. Overfilling or underfilling specimen tubes can change this
ratio. OBJECTIVES: The aim of this study was to determine the impact of under-
and overfilling citrate test tubes on ROTEM((r)) EXTEM measurements. RESULTS:
Overall repeated measures ANOVA demonstrated significant differences of CT (p =
0.004), CFT (p = 0.005), A5 (p = 0.001), A10 (p <0.001), and MCF (p < 0.001).
Pairwise comparison revealed that underfilling significantly altered the results
of those parameters reflecting functional clot firmness (A5, A10, and MCF), while
overfilling led to a prolongation of the CT results only. No differences were
observed for alpha angle and maximum lysis. CONCLUSION: Both underfilling and
overfilling specimen tubes have significant influence on the results of the
ROTEM((r)) EXTEM test, although the small observed bias is likely of limited
clinical relevance. However, it seems prudent to limit the maximum allowed
difference in filling to less than +/- 10%. All ROTEM((r)) operators should be
aware of this pre-analytical variable.
PMID- 26426853
TI - Fluorescent glutathione probe based on MnO2-phenol formaldehyde resin
nanocomposite.
AB - MnO2-phenol formaldehyde resin (MnO2-PFR) nanocomposite is successfully prepared
by a simple chemical reduction process. The resultant MnO2-PFR nanocomposite is
well characterized. The absorption band of non-fluorescent MnO2 nanosheets
overlaps well with the fluorescence emission of PFR nanoparticles. The green
fluorescence of PFR in this nanocomposite can be effectively quenched by
fluorescence resonance energy transfer from PFR to MnO2. In the presence of
glutathione (GSH), the fluorescence of PFR could be recovered due to MnO2 was
reduced to Mn(2+) by GSH. The nanocomposite can be use for detecting glutathione
in blood serum.
PMID- 26426855
TI - Self-reported benefit, sound perception, and quality-of-life in patients with
auditory brainstem implants (ABIs).
AB - CONCLUSION: The majority of the patients used their auditory brainstem implants
(ABIs) all the time, reporting that he/she would make the decision to receive an
implant again if the decision were reconsidered. The findings support that the
ABI is a valuable treatment in patients with type 2 neurofibromatosis (NF2) and
in children with congenital inner ear and nerve anomalies or cochlear
ossification. OBJECTIVE: To evaluate the patients who underwent ABI implantation
in Uppsala during 1993-2013. This study analyzed patients' implant use,
perception of environmental sounds, perceived benefit from the implant, and
quality-of-life (QoL). METHOD: The NF2-patients (n = 20) comprised the majority
of the patients, and there were a few non-NF2 pediatric patients (n = 4). The
exclusion criteria included deceased patients (n = 4) and patients with no
hearing sensations from the implant, or those with an inactivated ABI (n = 2).
The data were collected from a questionnaire survey. RESULTS: Eleven adult
patients and two pediatric patients answered the questionnaires. Eight of the
adult patients used their implants 'always'. The two children always used their
implants. Hearing problems had the largest negative effect on the QoL. The non
users and the users scored equally on the NFTI-QoL.
PMID- 26426854
TI - Implications of Heterogeneous Biting Exposure and Animal Hosts on Trypanosomiasis
brucei gambiense Transmission and Control.
AB - The gambiense form of sleeping sickness is a neglected tropical disease, which is
presumed to be anthroponotic. However, the parasite persists in human populations
at levels of considerable rarity and as such the existence of animal reservoirs
has been posited. Clarifying the impact of animal host reservoirs on the
feasibility of interrupting sleeping sickness transmission through interventions
is a matter of urgency. We developed a mathematical model allowing for
heterogeneous exposure of humans to tsetse, with animal populations that differed
in their ability to transmit infections, to investigate the effectiveness of two
established techniques, screening and treatment of at-risk populations, and
vector control. Importantly, under both assumptions, an integrated approach of
human screening and vector control was supported in high transmission areas.
However, increasing the intensity of vector control was more likely to eliminate
transmission, while increasing the intensity of human screening reduced the time
to elimination. Non-human animal hosts played important, but different roles in
HAT transmission, depending on whether or not they contributed as reservoirs. If
they did not serve as reservoirs, sensitivity analyses suggested their
attractiveness may instead function as a sink for tsetse bites. These outcomes
highlight the importance of understanding the ecological and environmental
context of sleeping sickness in optimizing integrated interventions, particularly
for moderate and low transmission intensity settings.
PMID- 26426856
TI - Adrenergic beta2-receptor mediates itch hypersensitivity following heterotypic
chronic stress in rats.
AB - Chronic stress is widely considered to trigger or enhance itch, especially for
pruritic dermatitis. However, the molecular mechanisms linking chronic stress and
itch are still unknown. The present study aimed to elucidate the role of
adrenergic signaling in itch hypersensitivity following heterotypic chronic
intermittent stress (HIS) in rats. HIS significantly increased hindlimb
scratching, but not forepaw swiping, induced by intradermal injection of 5
hydroxytryptamine (5-HT) in the rat cheek. Coadministration of stress mediators
such as norepinephrine or epinephrine dose-dependently increased both 5-HT
induced hindlimb scratching and 5-HT-induced forepaw swiping. HIS-induced itch
hypersensitivity was attenuated by blockade of sympathetic signaling through
guanethidine treatment, and systemic administration of the beta-adrenoceptor
antagonist propranolol and the beta2-adrenoceptor antagonist butoxamine, but not
on treatment with an alpha-adrenoceptor antagonist phentolamine and a beta1
adrenoceptor antagonist atenolol. Moreover, HIS selectively increased the
expression of beta2-adrenoceptors and proinflammatory factors [tumor necrosis
factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and nerve growth factor
(NGF)] in rat skin. The beta-blockers propranolol and butoxamine abolished the
upregulation of proinflammatory factors. The beta2-adrenoceptor agonist
terbutaline was sufficient to enhance the skin expression of TNF-alpha and IL
1beta and to increase 5-HT-induced scratching in naive rats. Pretreatment with
TNF-alpha could increase 5-HT-induced scratching. Together, these results
demonstrate that beta2-adrenoceptors mediate itch hypersensitivity following
chronic stress by inducing proinflammatory factors, such as TNF-alpha, in the
skin.
PMID- 26426857
TI - Brain contrasts between migratory and nonmigratory North American lark sparrows
(Chondestes grammacus).
AB - The impact of evolving migratory behavior on brain organization in birds has been
a foundational question in the emerging field of neuroecology. One generalization
that seems to be approaching consensus is that migratory species/populations have
smaller brain volumes than their nonmigratory comparison groups. The lark sparrow
(Chondestes grammacus) is a North American species characterized by migratory and
nonmigratory populations. Consistent with what has been observed in other
species/population comparisons, we found that, relative to body weight, migratory
females from Nebraska have smaller brain volumes than nonmigratory females from
Texas. We also carried out an exploratory, higher-order analysis of possible
differences in the volumes of a number of telencephalic subdivisions. Although
our small sample size precluded statistical verification of any difference,
noteworthy was that, although there seemed to be no indication of a difference in
the relative hippocampal volume between the two populations, the migratory birds
from Nebraska showed a clear trend toward a smaller nidopallium. The importance
of higher-resolution, brain subdivisional analyses has been discussed.
PMID- 26426858
TI - The influences of reappraisal and suppression instructions on memory for neutral
words in negative background.
AB - Previous studies have investigated the influences of emotion regulation on memory
for emotional stimuli. However, whether and how emotion regulation impacts
recognition memory for neutral items in negative background is still unclear.
Thus, the present study used event-related potentials and the study-recognition
memory task to examine the effects of the two commonly used emotion regulation
strategies, cognitive reappraisal and expressive suppression, on recognition
memory of neutral words centrally presented on negative pictures. The behavior
results showed that, compared with suppression, the reappraisal strategy enhanced
the neutral words memory. Moreover, the event-related potential data demonstrated
larger FN400 old/new effect indexing familiarity and late positive component
old/new effect presenting episodic information recollection for the reappraisal
condition relative to view and suppression conditions. These might be due to
significant elaboration encouraged by this strategy.
PMID- 26426860
TI - Water-Dispersible, Responsive, and Carbonizable Hairy Microporous Polymeric
Nanospheres.
AB - Multifunctionalization of microporous polymers is highly desirable but remains a
significant challenge, considering that the current microporous polymers are
generally hydrophobic and nonresponsive to different environmental stimuli and
difficult to be carbonized without damage of their well-defined nanomorphology.
Herein, we demonstrate a facile and versatile method to fabricate water
dispersible, pH/temperature responsive and readily carbonizable hairy microporous
polymeric nanospheres based on combination of the hyper-cross-linking chemistry
with the surface-initiated atom transfer radical polymerization (SI-ATRP). The
hyper-cross-linking creates a highly microporous core, whereas the SI-ATRP
provides diverse functionalities by surface grafting of hairy functional blocks.
The as-prepared materials present multifunctional properties, including sensitive
response to pH/temperature, high adsorption capacity toward adsorbates from
aqueous solution, and valuable transformation into well-defined microporous
carbon nanospheres because of hybrid of carbonizable core and thermo-decomposable
protection shell. We hope this strategy could promote the development of both
functional microporous polymers and advanced hairy nanoparticles for multipurpose
applications.
PMID- 26426859
TI - Tight junction disruption of blood-brain barrier in white matter lesions in
chronic hypertensive rats.
AB - Tight junctions (TJs) are the most important structure of the blood-brain barrier
(BBB). Studies have shown that triggering of white matter lesions (WMLs) may be
related to a BBB dysfunction, but rarely have studies observed the progressive
changes in TJs longitudinally. In our present study, the ultrastructure of TJs
was observed using a transmission electron microscope in Stroke-prone
Renalvascular Hypertensive Rats. Western blotting was used to detect TJ-related
proteins zonula occludens-1 and occludin. The results showed that in Stroke-prone
Renalvascular Hypertensive Rats, the severity of WMLs increased gradually. TJs
was destroyed gradually 8 weeks after hypertension. The levels of zonula
occludens-1 and occludin also decreased gradually. These data suggested that long
term hypertension may contribute toward the gradual disruption of TJs of BBB and
induce WMLs in chronic hypertensive rats.
PMID- 26426861
TI - Intravenous Delta-9-Tetrahydrocannabinol to Prevent Postoperative Nausea and
Vomiting: A Randomized Controlled Trial.
AB - BACKGROUND: Evidence suggests that cannabinoids can prevent chemotherapy-induced
nausea and vomiting. The use of tetrahydrocannabinol (THC) has also been
suggested for the prevention of postoperative nausea and vomiting (PONV), but
evidence is very limited and inconclusive. To evaluate the effectiveness of IV
THC in the prevention of PONV, we performed this double-blind, randomized,
placebo-controlled trial with patient stratification according to the risk of
PONV. Our hypothesis was that THC would reduce the relative risk of PONV by 25%
compared with placebo. METHODS: With IRB approval and written informed consent,
40 patients at high risk for PONV received either 0.125 mg/kg IV THC or placebo
at the end of surgery before emergence from anesthesia. The primary outcome
parameter was PONV during the first 24 hours after emergence. Secondary outcome
parameters included early and late nausea, emetic episodes and PONV, and side
effects such as sedation or psychotropic alterations. RESULTS: The relative risk
reduction of overall PONV in the THC group was 12% (95% confidence interval, -37%
to 43%), potentially less than the clinically significant 25% relative risk
reduction demonstrated by other drugs used for PONV prophylaxis. Calculation of
the effect of treatment group on overall PONV by logistic regression adjusted for
anesthesia time gave an odds ratio of 0.97 (95% confidence interval, 0.21 to
4.43, P = 0.97). Psychotropic THC side effects were clinically relevant and
mainly consisted of sedation and confusion that were not tampered by the effects
of anesthesia. The study was discontinued after 40 patients because of the
inefficacy of THC against PONV and the finding of clinically unacceptable side
effects that would impede the use of THC in the studied setting. CONCLUSIONS:
Because of an unacceptable side effect profile and uncertain antiemetic effects,
IV THC administered at the end of surgery before emergence from anesthesia cannot
be recommended for the prevention of PONV in high-risk patients.
PMID- 26426862
TI - A low-cost cementite (Fe3C) nanocrystal@N-doped graphitic carbon electrocatalyst
for efficient oxygen reduction.
AB - In this work, chitosan whiskers (CWs) were first extracted using low-cost and
earth-abundant crab shells as materials by a series of chemical processes, and
then assembled into chitosan whisker microspheres (CWMs) via a simple
photochemical polymerization approach. Subsequently, a cementite (Fe3C)
nanocrystal@N-doped graphitic carbon (Fe3C@NGC) nanocomposite was successfully
fabricated by high temperature pyrolysis of CWMs adsorbed with ferric
acetylacetonate (Fe(acac)3) at 900 degrees C. It was found that a suitable
growth atmosphere generated inside CWMs during high temperature pyrolysis is
critically important to form Fe3C nanocrystal cores, concurrently accompanying a
structural transformation from chitosan whiskers to mesoporous graphitic carbon
shells with natural nitrogen (N) doping properties, resulting in the formation of
a core-shell structure Fe3C@NGC nanocomposite. The resulting samples were
evaluated as electrocatalysts for oxygen reduction reaction (ORR). In comparison
with sole N-doped graphitic carbon without Fe3C nanocrystals obtained by direct
pyrolysis of chitosan whisker microspheres at 900 degrees C (CWMs-900), Fe3C@NGC
showed significantly improved ORR catalytic activity. The tolerance to fuel cell
molecules (e.g., methanol) and the durability of Fe3C@NGC are obviously superior
to commercial Pt/C catalysts in alkaline media. The high ORR performance of
Fe3C@NGC could be due to its large surface area (313.7 m(2) g(-1)), a synergistic
role of Fe3C nanocrystals, N doping in graphitic carbon creating more catalytic
active sites, and a porous structure of the nanocomposite facilitating mass
transfer to efficiently improve the utilization of these catalytic active sites.
PMID- 26426863
TI - Tuberculin reaction and BCG scar: association with infant mortality.
AB - OBJECTIVE: To test the hypothesis that having a scar and a positive tuberculin
skin test (TST) response after vaccination with Bacille Calmette-Guerin (BCG) is
associated with reduced infant mortality. METHODS: We studied cohorts of 2709
normal-birthweight (NBW) and 1102 low-birthweight (LBW) infants in Guinea-Bissau.
Children were enrolled in randomised trials between year 2002 and 2008 and
received BCG vaccination at birth. BCG scars and TST responses were assessed at 2
and 6 months of age. The infants were followed for mortality to 12 months of age,
and survival was analysed using Cox regression. RESULTS: At age 2 months, 88% of
NBW children and 91% of LBW children had a BCG scar, and 36% and 17% had a TST
response, respectively. The LBW infants had nearly twofold higher mortality
(4.5%) than the NBW infants (2.8%) between 2 and 12 months of age. In the LBW
cohort, the adjusted mortality rate ratio (MRR) comparing children with a BCG
scar with those without was 0.42 (95% CI = 0.19; 0.93). There was a similar
tendency for TST positivity: MRR = 0.47 (95% CI = 0.14; 1.54). For LBW children
who had both a positive TST reaction and a scar, the MRR was 0.22 (95% CI = 0.05;
0.87). For NBW children, a scar and a positive TST were associated with 20%
reductions in mortality, which did not reach statistical significance.
CONCLUSION: We confirmed previous observations that having a scar and a TST
response after BCG vaccination is associated with lower mortality risk. The
possibility of revaccinating scar-negative children should be considered.
PMID- 26426864
TI - Rapid Determination of the Specificity Constant of Irreversible Inhibitors
(kinact/KI) by Means of an Endpoint Competition Assay.
AB - Owing to their covalent target occupancy, irreversible inhibitors require low
exposures and offer long duration, and their use thus represents a powerful
strategy for achieving pharmacological efficacy. Importantly, the potency metric
of irreversible inhibitors is kinact/KI not IC50. A simple approach to measuring
kinact/KI was developed that makes use of an irreversible probe for competitive
assays run to completion against test compounds. In this system, the kinact/KI
value of the test compound is equal to (kinact/KI)probe *[probe]/IC50. The
advantages of this method include simplicity, high throughput, and application to
all target classes, and it only requires an in-depth kinetic evaluation of the
probe.
PMID- 26426866
TI - Establishment of a specific cell death induction system in Bombyx mori by a
transgene with the conserved apoptotic regulator, mouse Bcl-2-associated X
protein (mouse Bax).
AB - The induction of apoptosis in vivo is a useful tool for investigating the
functions and importance of particular tissues. B-cell leukaemia/lymphoma 2
associated X protein (Bax) functions as a pro-apoptotic factor and induces
apoptosis in several organisms. The Bax-mediated apoptotic system is widely
conserved from Caenorhabditis elegans to humans. In order to establish a tissue
specific cell death system in the domestic silkworm, Bombyx mori, we constructed
a transgenic silkworm that overexpressed mouse Bax (mBax) in particular tissues
by the Gal4-upstream activation sequence system. We found that the expression of
mBax induced specific cell death in the silk gland, fat body and sensory cells.
Fragmentation of genomic DNA was observed in the fat body, which expressed mBax,
thereby supporting apoptotic cell death in this tissue. Using this system, we
also demonstrated that specific cell death in sensory cells attenuated the
response to the sex pheromone bombykol. These results show that we successfully
established a tissue-specific cell death system in vivo that enabled specific
deficiencies in particular tissues. The inducible cell death system may provide
useful means for industrial applications of the silkworm and possible utilization
for other species.
PMID- 26426865
TI - Prognostic and mechanistic potential of progesterone sulfates in intrahepatic
cholestasis of pregnancy and pruritus gravidarum.
AB - A challenge in obstetrics is to distinguish pathological symptoms from those
associated with normal changes of pregnancy, typified by the need to
differentiate whether gestational pruritus of the skin is an early symptom of
intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum.
ICP is characterized by raised serum bile acids and complicated by spontaneous
preterm labor and stillbirth. A biomarker for ICP would be invaluable for early
diagnosis and treatment and to enable its differentiation from other maternal
diseases. Three progesterone sulfate compounds, whose concentrations have not
previously been studied, were newly synthesized and assayed in the serum of three
groups of ICP patients and found to be significantly higher in ICP at 9-15 weeks
of gestation and prior to symptom onset (group 1 cases/samples: ICP n = 35/80,
uncomplicated pregnancy = 29/100), demonstrating that all three progesterone
sulfates are prognostic for ICP. Concentrations of progesterone sulfates were
associated with itch severity and, in combination with autotaxin, distinguished
pregnant women with itch that would subsequently develop ICP from pruritus
gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of
first-trimester samples all progesterone sulfates were significantly elevated in
serum from low-risk asymptomatic women who subsequently developed ICP
(ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that
progesterone sulfates mediate itch by evoking a Tgr5-dependent scratch response
in mice. CONCLUSION: Our discovery that sulfated progesterone metabolites are a
prognostic indicator for ICP will help predict onset of ICP and distinguish it
from benign pruritus gravidarum, enabling targeted obstetric care to a high-risk
population. Delineation of a progesterone sulfate-TGR5 pruritus axis identifies a
therapeutic target for itch management in ICP.
PMID- 26426867
TI - Pneumothorax in a dog caused by necrotizing pneumonia secondary to heatstroke.
AB - OBJECTIVE: To describe the clinical course, diagnostic findings, medical and
surgical treatments, and outcome in a dog with spontaneous pneumothorax secondary
to necrotizing pneumonia thought to be a delayed complication of heatstroke. CASE
SUMMARY: A 1.5-year-old Labrador Retriever developed spontaneous pneumothorax 12
days after an episode of exertional heat stroke. Computed tomography was
performed and showed bilateral pneumothorax and multifocal pulmonary
consolidation, especially at the lung periphery. A median sternotomy was
performed, and multifocal, well-demarcated areas of consolidated pulmonary tissue
with purple discoloration were identified and resected from the right middle,
right caudal, and accessory lung lobes. Histologic examination of the resected
pulmonary tissue indicated necrotizing pneumonia, and bacteriologic culture of
the tissue resulted in growth of Pseudomonas aeruginosa. Examination of tissue
from a pectoral muscle biopsy performed at this time showed necrotizing myopathy.
The dog was discharged 7 days after surgery and made a full recovery. NEW OR
UNIQUE INFORMATION PROVIDED: This case report describes pneumothorax and
multifocal necrotizing pneumonia as a delayed complication of heatstroke, and
provides the first description of the computed tomography appearance of
histologically confirmed necrotizing pneumonia in a dog. Multifocal necrotizing
pneumonia with or without pneumothorax should be considered in dogs that develop
respiratory distress following severe systemic illness.
PMID- 26426869
TI - News from the pediatric anesthesia societies: the Congenital Cardiac Anesthesia
Society.
PMID- 26426870
TI - The puzzling aspects of anesthesia and autism spectrum disorder.
PMID- 26426871
TI - Why rare diseases are of special interest to pediatric anesthesiologists.
PMID- 26426872
TI - Response to Dr A Snoek - 'Useful as a point-of-care algorithm?'.
PMID- 26426873
TI - Useful as a point-of-care algorithm?
PMID- 26426874
TI - Response to editorial comments by Drs. Williams and Ramamoorthy.
PMID- 26426875
TI - Surveys and all--the role of pediatric anesthetic societies.
PMID- 26426876
TI - Reply to Engelhardt, Thomas; Wolf, Andy, regarding their comment 'Surveys and all
-the role of pediatric anesthetic societies'.
PMID- 26426877
TI - Evaluating the efficacy and safety of scalp blocks in nonsyndromic
craniosynostosis surgery.
PMID- 26426878
TI - Laryngospasm notch pressure ('Larson's maneuver') may have a role in laryngospasm
management in children: highlighting a so far unproven technique.
PMID- 26426879
TI - Is the supraclavicular approach to the central vein still risky and taboo?
PMID- 26426880
TI - Anesthesia and the developing brain: a way forward for clinical research.
PMID- 26426881
TI - Globotriaosylceramide inhibits iNKT-cell activation in a CD1d-dependent manner.
AB - Globotriaosylceramide (Gb3) is a glycosphingolipid present in cellular membranes
that progressively accumulates in Fabry disease. Invariant Natural Killer T
(iNKT) cells are a population of lipid-specific T cells that are phenotypically
and functionally altered in Fabry disease. The mechanisms responsible for the
iNKT-cell alterations in Fabry disease are not well understood. Here, we analyzed
the effect of Gb3 on CD1d-mediated iNKT-cell activation in vitro using human
cells and in vivo in the mouse model. We found that Gb3 competes with endogenous
and exogenous antigens for CD1d binding, thereby reducing the activation of iNKT
cells. This effect was exerted by a reduction in the amount of stimulatory
CD1d:alpha-GalCer complexes in the presence of Gb3 as demonstrated by using an
mAb specific for the complex. We also found that administration of Gb3 delivered
to the same APC as alpha-GalCer, induces reduced iNKT-cell activation in vivo.
This work highlights the complexity of iNKT-cell activation and the importance of
nonantigenic glycosphingolipids in the modulation of this process.
PMID- 26426882
TI - Determination of Intermolecular Interactions Using Polarization Compensated
Heteronuclear Overhauser Effect of Hyperpolarized Spins.
AB - The nuclear Overhauser effect (NOE) has long been used as a selective indicator
for intermolecular interactions. Due to relatively small changes of signal
intensity, often on the order of several percent, quantitative NOE measurements
can be challenging. Hyperpolarization of nuclear spins can dramatically increase
the NOE intensity by increasing population differences, but poses its own
challenge in quantifying the original polarization level. Here, we demonstrate a
method for the accurate measurement of intermolecular heteronuclear cross
relaxation rates by simultaneous acquisition of signals from both nuclei. Using
this method, we measure cross-relaxation rates between water protons and (19)F of
trifluoroacetic acid at concentrations ranging from 23 to 72 mM. A concentration
independent value of 2.46 * 10(-4) +/- 1.02 * 10(-5) s(-1) M(-1) is obtained at a
temperature of 301 K and validated using a nonhyperpolarized measurement. In a
broader context, accurate measurement of heteronuclear cross-relaxation rates may
enable the study of intermolecular interactions including those involving
macromolecules where (19)F atoms can be introduced as site-selective labels.
PMID- 26426883
TI - Multigene panels in prostate cancer risk assessment: a systematic review.
AB - PURPOSE: Single-nucleotide polymorphism (SNP) panel tests have been proposed for
use in the detection of, and prediction of risk for, prostate cancer and as
prognostic indicator in affected men. A systematic review was undertaken to
address three research questions to evaluate the analytic validity, clinical
validity, clinical utility, and prognostic validity of SNP-based panels. METHODS:
Data sources comprised MEDLINE, Cochrane CENTRAL, Cochrane Database of Systematic
Reviews, and EMBASE; these were searched from inception to April 2013. The gray
literature searches included contact with manufacturers. Eligible studies
included English-language studies evaluating commercially available SNP panels.
Study selection and risk of bias assessment were undertaken by two independent
reviewers. RESULTS: Twenty-one studies met eligibility criteria. All focused on
clinical validity and evaluated 18 individual panels with 2 to 35 SNPs. All had
poor discriminative ability (overall area under receiver-operator characteristic
curves, 58-74%; incremental gain resulting from inclusion of SNP data, 2.5-11%)
for predicting risk of prostate cancer and/or distinguishing between aggressive
and asymptomatic/latent disease. The risk of bias of the studies, as assessed by
the Newcastle Ottawa Scale (NOS) and Quality Assessment of Diagnostic Accuracy
Studies (QUADAS) tools, was moderate. CONCLUSION: The evidence on currently
available SNP panels is insufficient to assess analytic validity, and at best the
panels assessed would add a small and clinically unimportant improvement to
factors such as age and family history in risk stratification (clinical
validity). No evidence on the clinical utility of current panels is
available.Genet Med 18 6, 535-544.
PMID- 26426885
TI - Magnetic nanoparticles for biomedical applications.
PMID- 26426886
TI - Mild cognitive impairment affects motor control and skill learning.
AB - Mild cognitive impairment (MCI) is a transitional phase between normal cognitive
aging and dementia. As the world population is aging rapidly, more MCI patients
will be identified, posing significant problems to society. Normal aging is
associated with cognitive and motor decline, and MCI brings additional
impairments. Compared to healthy older adults, MCI patients show poorer motor
control in a variety of tasks. Efficient motor control and skill learning are
essential for occupational and leisure purposes; degradation of motor behaviors
in MCI patients often adversely affects their health and quality of life. In this
article, we first define MCI and describe its pathology and neural correlates.
After this, we review cognitive changes and motor control and skill learning in
normal aging. This section is followed by a discussion of MCI-related degradation
of motor behaviors. Finally, we propose that multicomponent interventions
targeting both cognitive and motor domains can improve MCI patients' motor
functions. Future research directions are also raised.
PMID- 26426884
TI - Cesarean delivery is not associated with decreased at-birth fracture rates in
osteogenesis imperfecta.
AB - PURPOSE: Osteogenesis imperfecta (OI) predisposes to recurrent fractures.
Patients with the moderate to severe forms of OI present with antenatal
fractures, and the mode of delivery that would be safest for the fetus is not
known. METHODS: We conducted systematic analyses of the largest cohort of
individuals with OI (n = 540) enrolled to date in the OI Linked Clinical Research
Centers. Self-reported at-birth fracture rates were compared among individuals
with OI types I, III, and IV. Multivariate analyses utilizing backward
elimination logistic regression model building were performed to assess the
effect of multiple covariates, including method of delivery, on fracture-related
outcomes. RESULTS: When accounting for other covariates, at-birth fracture rates
did not differ based on whether delivery was by vaginal route or by cesarean
delivery (CD). Increased birth weight conferred higher risk for fractures
irrespective of the delivery method. In utero fracture, maternal history of OI,
and breech presentation were strong predictors for choosing CD. CONCLUSION: Our
study, the largest to analyze the effect of various factors on at-birth fracture
rates in OI, shows that CD is not associated with decreased fracture rate. With
the limitation that the fracture data were self-reported in this cohort, these
results suggest that CD should be performed only for other maternal or fetal
indications, not for the sole purpose of fracture prevention in OI.Genet Med 18
6, 570-576.
PMID- 26426888
TI - Cannabis - the Israeli perspective.
AB - Short overviews are presented on the historical uses of cannabis in the Middle
East and on the more recent scientific and medical research on phytocannabinoids
and the endocannabinoid system, with emphasis on research contributions from
Israel. These are followed by examples of research projects and clinical trials
with cannabinoids and by a short report on the regulation of medical marijuana in
Israel, which at present is administered to over 22,000 patients.
PMID- 26426887
TI - Targeting the endocannabinoid system to treat anxiety-related disorders.
AB - The endocannabinoid system plays an important role in the control of emotions,
and its dysregulation has been implicated in several psychiatric disorders. The
most common self-reported reason for using cannabis is rooted in its ability to
reduce feelings of stress, tension, and anxiety. Nevertheless, there are only few
studies in controlled clinical settings that confirm that administration of
cannabinoids can benefit patients with a post-traumatic stress disorder (PTSD).
There are considerable encouraging preclinical data to suggest that
endocannabinoid-targeted therapeutics for anxiety disorders should continue. In
this review, we will describe data supporting a role for the endocannabinoid
system in preventing and treating anxiety-like behavior in animal models and PTSD
patients. Cannabinoids have shown beneficial outcomes in rat and mouse models of
anxiety and PTSD, but they also may have untoward effects that discourage their
chronic usage, including anxiogenic effects. Hence, clinical and preclinical
research on the endocannabinoid system should further study the effects of
cannabinoids on anxiety and help determine whether the benefits of using
exogenous cannabinoids outweigh the risks. In general, this review suggests that
targeting the endocannabinoid system represents an attractive and novel approach
to the treatment of anxiety-related disorders and, in particular, PTSD.
PMID- 26426889
TI - Synthesis of androstanopyridine and pyrimidine compounds as novel activators of
the tumor suppressor protein p53.
AB - A series of androstane derivatives 2-16 were synthesized from 3beta
hydroxyandrostan-17-one derivatives (1a-e). Compounds (1a,b) were treated with
ethyl cyanoacetate, cyanoacetamide, or malononitrile and gave the corresponding
derivatives 2-7, respectively. Additionally, compounds (1a-e) were condensed with
cyanothioacetamide, urea, or guanidine hydrochloride afforded the corresponding
derivatives 8-12, which then by Moffat oxidation gave the oxidized derivatives 9,
11 and 13, respectively. Finally, compound (1) condensed with acetyl acetone or
ethyl acetoacetate gave cyclohexene derivatives (14a-c) and (15a,b),
respectively. Compound 15 was oxidized with a Moffat oxidizing agent and afforded
the corresponding oxidized compound 16. The newly synthesized compounds activated
the tumor suppressor p53 in cancer cells through inhibition of the p53-specific
ubiquitin E3 ligase HDM2.
PMID- 26426890
TI - Comparison between B.R.A.H.M.S PCT direct, a new sensitive point-of-care testing
device for rapid quantification of procalcitonin in emergency department patients
and established reference methods - a prospective multinational trial.
AB - BACKGROUND: Procalcitonin (PCT) is increasingly being used for the diagnostic and
prognostic work up of patients with suspected infections in the emergency
department (ED). Recently, B.R.A.H.M.S PCT direct, the first high sensitive point
of-care test (POCT), has been developed for fast PCT measurement on capillary or
venous blood samples. METHODS: This is a prospective, international comparison
study conducted in three European EDs. Consecutive patients with suspicion of
bacterial infection were included. Duplicate determination of PCT was performed
in capillary (fingertip) and venous whole blood (EDTA), and compared to the
reference method. The diagnostic accuracy was evaluated by correlation and
concordance analyses. RESULTS: Three hundred and three patients were included
over a 6-month period (60.4% male, median age 65.2 years). The correlation
between capillary or venous whole blood and the reference method was excellent:
r2=0.96 and 0.97, sensitivity 88.1% and 93.0%, specificity 96.5% and 96.8%,
concordance 93% and 95%, respectively at a 0.25 MUg/L threshold. No significant
bias was observed (-0.04 and -0.02 for capillary and venous whole blood) although
there were 6.8% and 5.1% outliers, respectively. B.R.A.H.M.S PCT direct had a
shorter time to result as compared to the reference method (25 vs. 144 min,
difference 119 min, 95% CI 110-134 min, p<0.0001). CONCLUSIONS: This study found
a high diagnostic accuracy and a faster time to result of B.R.A.H.M.S PCT direct
in the ED setting, allowing shortening time to therapy and a more wide-spread use
of PCT.
PMID- 26426891
TI - Non-fasting plasma glucose concentration in blood donors.
PMID- 26426892
TI - Croatian laboratories have a good knowledge of the proper detection and
management of hemolyzed, icteric and lipemic samples.
AB - BACKGROUND: Endogenous interferences are an important source of biased laboratory
results. Hemolysis, lipemia and icteria are the main source of endogenous
interference in laboratory medicine. Accreditation according to ISO 15189
improves the overall quality of the laboratory procedures. The aim of our study
was i) to assess the level of knowledge of Croatian medical biochemists about the
proper detection and management of hemolysis, lipemia and icteria; and ii) to
identify possible differences in the level of knowledge respective to the
laboratory accreditation status. METHODS: An on-line self-report survey was
carried out by the Working Group for Preanalytical Phase of the Croatian Society
of Medical Biochemistry and Laboratory Medicine during April to May 2015. Survey
included 14 statements (Q1-Q14) about procedures for samples with interferences
and participants were asked to assess the degree of agreement with the statement
using a 4-point Likert scale. RESULTS: The lowest level of knowledge was observed
for statements Q10 (dealing with icteric sample; 40.9% participants agreed with
the correct procedure), Q12 (allowable error for interference; 47.2%) and Q11
(dealing with lipemic sample; 60.1%). Almost all participants (97.4%) agreed that
laboratories in Croatia should have a harmonized protocol for management of
samples with interferences. Participants from accredited laboratories showed
higher knowledge of hemolysis detection (p=0.031), rejection of hemolyzed sample
(p<0.001), management of icteric samples (p=0.038) and allowable error for
interferences (p=0.040). CONCLUSIONS: Croatian laboratories have a good knowledge
of the proper detection and management of hemolyzed, icteric and lipemic samples.
Accreditation is associated with higher knowledge about management of samples
with interferences.
PMID- 26426893
TI - Useful measures and models for analytical quality management in medical
laboratories.
AB - The 2014 Milan Conference "Defining analytical performance goals 15 years after
the Stockholm Conference" initiated a new discussion of issues concerning goals
for precision, trueness or bias, total analytical error (TAE), and measurement
uncertainty (MU). Goal-setting models are critical for analytical quality
management, along with error models, quality-assessment models, quality-planning
models, as well as comprehensive models for quality management systems. There are
also critical underlying issues, such as an emphasis on MU to the possible
exclusion of TAE and a corresponding preference for separate precision and bias
goals instead of a combined total error goal. This opinion recommends careful
consideration of the differences in the concepts of accuracy and traceability and
the appropriateness of different measures, particularly TAE as a measure of
accuracy and MU as a measure of traceability. TAE is essential to manage quality
within a medical laboratory and MU and trueness are essential to achieve
comparability of results across laboratories. With this perspective, laboratory
scientists can better understand the many measures and models needed for
analytical quality management and assess their usefulness for practical
applications in medical laboratories.
PMID- 26426894
TI - Development of reference intervals for serum alkaline phosphatase among adults in
Southern China traced to the new IFCC reference measurement procedure.
AB - BACKGROUND: Serum alkaline phosphatase (ALP) plays a critical role in the
diagnosis of various diseases, and the establishment of relevant, reliable
reference intervals (RI) is key to avoiding misdiagnoses. In 2011, IFCC published
the new reference measurement procedure (RMP) for the determination of serum ALP
in which one of the main modifications was the measuring temperature of the
assay. Here, the new RMP was used to help establish RIs for serum ALP
concentrations in healthy Chinese Han. METHODS: Volunteer individuals in
Guangdong province, China (n=1622) were screened by questionnaire and laboratory
testing for eligibility as a reference. Blood (20 mL) was collected and samples
were measured by the Roche Modular system using the new RMP for the serum ALP
compatible method. Partitioning of values by gender and/or age was evaluated with
a standard normal deviate test after removing outliers. A simple non-parametric
method for a two-sided 95% distribution of reference values was calculated.
RESULTS: Serum ALP concentrations were obtained from the cohort of eligible
reference individuals (n=658). The RI for serum ALP in males age 18-79 years was
48-131 U/L. Females were partitioned into two age groups based on statistical
analysis, 18-49 years and 50-79 years, and the RIs derived were 40-106 U/L and 57
159 U/L, respectively. CONCLUSIONS: RIs for serum ALP for Chinese Han individuals
in between the ages of 18 and 79 years were determined and required partitioning
due to the higher ALP values of females age 50-79 years.
PMID- 26426895
TI - Birth season predicts the values of red blood cell distribution width (RDW) in
adulthood.
AB - BACKGROUND: Recent evidence suggests that red blood cell distribution width
(RDW), a simple measure of anisocytosis, may predict the risk of adverse clinical
outcomes in both the general population and in patients with severe pathologies.
Since it was also shown that the birth season influences the lifetime disease
risk, this study was aimed to investigate whether an association may exist
between adult RDW values and birth season. METHODS: The study population
consisted in healthy Caucasian blood donors aged 18 or older, undergoing routine
laboratory testing before regular blood donation. RESULTS: Overall, 6122 healthy
blood donors were included in this study (median age 41 years; 1807 women and
4315 men). Age, sex, mean corpuscular volume (MCV) and mean corpuscular
hemoglobin (MCH) but not hemoglobin and hematocrit were found to be independent
predictors of RDW. When the study population was classified according to birth
season, a significant difference was found for RDW values, but not for age, sex,
hemoglobin, hematocrit, MCV and MCH. Subjects born in spring exhibited RDW values
generally higher compared to those born in other seasons, reaching statistical
significance when compared to those born in summer and winter. In particular,
subjects born in spring had a 33% (p=0.014) higher probability of displaying
increased RDW values in adulthood compared to those with summer birth.
CONCLUSIONS: Despite additional studies that are needed to confirm these original
findings, the evidence that a significant link exists between birth season and
adult anisocytosis provides a plausible explanation for the association between
birth season and lifetime disease risk.
PMID- 26426896
TI - A robust distribution-free test for genetic association studies of quantitative
traits.
AB - In association studies of quantitative traits, the association of each genetic
marker with the trait of interest is typically tested using the F-test assuming
an additive genetic model. In practice, the true model is rarely known, and
specifying an incorrect model can lead to a loss of power. For case-control
studies, the maximum of test statistics optimal for additive, dominant, and
recessive models has been shown to be robust to model misspecification. The
approach has later been extended to quantitative traits. However, the existing
procedures assume that the trait is normally distributed and may not maintain
correct type I error rates and can also have reduced power when the assumption of
normality is violated. Here, we introduce a maximum (MAX3) test that is based on
ranks and is therefore distribution-free. We examine the behavior of the proposed
method using a Monte Carlo simulation with both normal and non-normal data and
compare the results to the usual parametric procedures and other nonparametric
alternatives. We show that the rank-based maximum test has favorable properties
relative to other tests, especially in the case of symmetric distributions with
heavy tails. We illustrate the method with data from a real association study of
symmetric dimethylarginine (SDMA).
PMID- 26426897
TI - Likelihood ratio and score burden tests for detecting disease-associated rare
variants.
AB - This paper presents two simple rare variant (RV) burden tests based on the
likelihood ratio test (LRT) and score statistics. LRT is one of the commonly used
tests in practical data analysis, and we show here that there is no reason to
ignore it in testing RV associations. With the Bartlett correction, we have
numerically shown that the LRT-based test can have a reliable distribution. Our
simulation study indicates that if the non-null variants are as common as the
null variants, then the LRT and score statistics have comparable performance to
the C-alpha test, and if the former is rarer than the null variants, then they
outperform the C-alpha test.
PMID- 26426898
TI - Plant responses to climatic extremes: within-species variation equals among
species variation.
AB - Within-species and among-species differences in growth responses to a changing
climate have been well documented, yet the relative magnitude of within-species
vs. among-species variation has remained largely unexplored. This missing
comparison impedes our ability to make general predictions of biodiversity change
and to project future species distributions using models. We present a direct
comparison of among- versus within-species variation in response to three of the
main stresses anticipated with climate change: drought, warming, and frost. Two
earlier experiments had experimentally induced (i) summer drought and (ii) spring
frost for four common European grass species and their ecotypes from across
Europe. To supplement existing data, a third experiment was carried out, to
compare variation among species from different functional groups to within
species variation. Here, we simulated (iii) winter warming plus frost for four
grasses, two nonleguminous, and two leguminous forbs, in addition to eleven
European ecotypes of the widespread grass Arrhenatherum elatius. For each
experiment, we measured: (i) C/N ratio and biomass, (ii) chlorophyll content and
biomass, and (iii) plant greenness, root (15) N uptake, and live and dead tissue
mass. Using coefficients of variation (CVs) for each experiment and response
parameter, a total of 156 within- vs. among-species comparisons were conducted,
comparing within-species variation in each of four species with among-species
variation for each seed origin (five countries). Of the six significant
differences, within-species CVs were higher than among-species CVs in four cases.
Partitioning of variance within each treatment in two of the three experiments
showed that within-species variability (ecotypes) could explain an additional 9%
of response variation after accounting for the among-species variation. Our
observation that within-species variation was generally as high as among-species
variation emphasizes the importance of including both within- and among-species
variability in ecological theory (e.g., the insurance hypothesis) and for
practical applications (e.g., biodiversity conservation).
PMID- 26426899
TI - Galactose-alpha-1,3-Galactose Allergy Is Not a Hitherto Unrecognized Cause of
Chronic Spontaneous Urticaria.
AB - BACKGROUND: Tick bite-induced galactose-alpha-1,3-galactose (alpha-Gal) IgE and
subsequent ingestion of red meat may cause delayed severe allergic reactions
including urticaria, gastrointestinal symptoms or anaphylaxis. We tested the
hypothesis that increased levels of IgE to alpha-Gal due to tick bites and the
subsequent ingestion of red meat or meat products may possibly be an
un(der)recognized cause of chronic spontaneous urticaria (CSU). METHODS: Levels
of IgE to alpha-Gal and total IgE were measured (ImmunoCAP, Phadia AB/Thermo
Fisher Scientific) in 83 patients (61 female and 22 male, median age 43 years,
range 18-82) from the Department of Dermatology and Allergy, Charite -
Universitatsmedizin, Berlin, Germany. All had been clinically diagnosed with
moderate-to-severe CSU of a median duration of 2.9 years (range 0.1-50). RESULTS:
Eighty of the 83 patients (96%) had undetectable (<0.1 kUA/l) serum levels of IgE
against alpha-Gal. The levels in the remaining 3 were all low (0.25, 0.4 and 3.1
kUA/l). In no patient, including those with measurable serum levels of IgE
against alpha-Gal, was eating red meat associated with the development of
symptoms of urticaria. CONCLUSION: Our results indicate that an allergic response
to alpha-Gal is highly unlikely to be a hitherto unrecognized common cause of
CSU.
PMID- 26426900
TI - Inhibitory Effects of Green Tea and (-)-Epigallocatechin Gallate on Transport by
OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-Glycoprotein.
AB - Green tea catechins inhibit the function of organic anion transporting
polypeptides (OATPs) that mediate the uptake of a diverse group of drugs and
endogenous compounds into cells. The present study was aimed at investigating the
effect of green tea and its most abundant catechin epigallocatechin gallate
(EGCG) on the transport activity of several drug transporters expressed in
enterocytes, hepatocytes and renal proximal tubular cells such as OATPs, organic
cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), and P
glycoprotein (P-gp). Uptake of the typical substrates metformin for OCTs and
MATEs and bromosulphophthalein (BSP) and atorvastatin for OATPs was measured in
the absence and presence of a commercially available green tea and EGCG.
Transcellular transport of digoxin, a typical substrate of P-gp, was measured
over 4 hours in the absence and presence of green tea or EGCG in Caco-2 cell
monolayers. OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was
significantly reduced in the presence of green tea and EGCG (P < 0.05). BSP net
uptake by OATP1B1 and OATP1B3 was inhibited by green tea [IC50 2.6% (v/v) and
0.39% (v/v), respectively]. Green tea also inhibited OATP1B1- and OATP1B3
mediated atorvastatin net uptake with IC50 values of 1.9% (v/v) and 1.0% (v/v),
respectively. Basolateral to apical transport of digoxin was significantly
decreased in the presence of green tea and EGCG. These findings indicate that
green tea and EGCG inhibit multiple drug transporters in vitro. Further studies
are necessary to investigate the effects of green tea on prototoypical substrates
of these transporters in humans, in particular on substrates of hepatic uptake
transporters (e.g. statins) as well as on P-glycoprotein substrates.
PMID- 26426901
TI - Population Trends of Central European Montane Birds Provide Evidence for Adverse
Impacts of Climate Change on High-Altitude Species.
AB - Climate change is among the most important global threats to biodiversity and
mountain areas are supposed to be under especially high pressure. Although recent
modelling studies suggest considerable future range contractions of montane
species accompanied with increased extinction risk, data allowing to test actual
population consequences of the observed climate changes and identifying traits
associated to their adverse impacts are very scarce. To fill this knowledge gap,
we estimated long-term population trends of montane birds from 1984 to 2011 in a
central European mountain range, the Giant Mountains (Krkonose), where
significant warming occurred over this period. We then related the population
trends to several species' traits related to the climate change effects. We found
that the species breeding in various habitats at higher altitudes had more
negative trends than species breeding at lower altitudes. We also found that the
species moved upwards as a response to warming climate, and these altitudinal
range shifts were associated with more positive population trends at lower
altitudes than at higher altitudes. Moreover, long-distance migrants declined
more than residents or species migrating for shorter distances. Taken together,
these results indicate that the climate change, besides other possible
environmental changes, already influences populations of montane birds with
particularly adverse impacts on high-altitude species such as water pipit (Anthus
spinoletta). It is evident that the alpine species, predicted to undergo serious
climatically induced range contractions due to warming climate in the future,
already started moving along this trajectory.
PMID- 26426903
TI - Causes and Consequences of Schadenfreude and Sympathy: A Developmental Analysis.
AB - Moral judgments and moral emotions are a ubiquitous feature of social
interactions. Humans decide quickly and intuitively whether an action is morally
right or wrong. Schadenfreude and sympathy, as emotional reactions to the
misfortunes of others, are prototypical moral emotions. So far, however, little
evidence exists concerning children's understanding of schadenfreude. Within
three studies, we investigated the experience of schadenfreude and sympathy among
N = 364 children of different age groups. We interviewed the children while
showing them picture stories. In the picture stories, we varied the behavior of
the protagonist prior to a misfortune: (1) whether his behavior had been morally
right or wrong, (2) whether the protagonist attained his goal, (3) whether the
protagonist was responsible for the misfortune. In addition, in one study we
varied (4) the emotional relationship of the interviewed children to the
protagonist. Furthermore, we asked the children to decide whether they want to
sit next to the protagonist or do him a favor. Results show that children
experience sympathy as well as schadenfreude at the age of 4 years. Sympathy is
more likely to arise when the protagonists of a story are likable, when these
actors typically pursue morally positive goals, and if they are not responsible
for their misfortune. In contrast, schadenfreude is more likely when the
protagonist is disliked, when actors pursue immoral goals and if they are
responsible for their misfortune. In addition, sympathy increases approach
(helping behavior, sitting next to the agent and doing favors), whereas
schadenfreude increases avoidance tendencies.
PMID- 26426902
TI - N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress
on the Gut Microbiota.
AB - BACKGROUND: Early life stress is a risk factor for many psychiatric disorders
ranging from depression to anxiety. Stress, especially during early life, can
induce dysbiosis in the gut microbiota, the key modulators of the bidirectional
signalling pathways in the gut-brain axis that underline several
neurodevelopmental and psychiatric disorders. Despite their critical role in the
development and function of the central nervous system, the effect of n-3
polyunsaturated fatty acids (n-3 PUFAs) on the regulation of gut-microbiota in
early-life stress has not been explored. METHODS AND RESULTS: Here, we show that
long-term supplementation of eicosapentaenoic acid (EPA)/docosahexaenoic acid
(DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture could restore the disturbed gut
microbiota composition of maternally separated (MS) female rats. Sprague-Dawley
female rats were subjected to an early-life stress, maternal separation procedure
from postnatal days 2 to 12. Non-separated (NS) and MS rats were administered
saline, EPA/DHA 0.4 g/kg/day or EPA/DHA 1 g/kg/day, respectively. Analysis of the
gut microbiota in adult rats revealed that EPA/DHA changes composition in the MS,
and to a lesser extent the NS rats, and was associated with attenuation of the
corticosterone response to acute stress. CONCLUSIONS: In conclusion, EPA/DHA
intervention alters the gut microbiota composition of both neurodevelopmentally
normal and early-life stressed animals. This study offers insights into the
interaction between n-3 PUFAs and gut microbes, which may play an important role
in advancing our understanding of disorders of mood and cognitive functioning,
such as anxiety and depression.
PMID- 26426905
TI - A Symposium in Honor of Richard G. Powell, a Long-Time Associate Editor of the
Journal of Natural Products.
PMID- 26426904
TI - The Effect of Comorbidity on Glycemic Control and Systolic Blood Pressure in Type
2 Diabetes: A Cohort Study with 5 Year Follow-Up in Primary Care.
AB - AIMS: To explore the longitudinal effect of chronic comorbid diseases on glycemic
control (HbA1C) and systolic blood pressure (SBP) in type 2 diabetes patients.
METHODS: In a representative primary care cohort of patients with newly diagnosed
type 2 diabetes in The Netherlands (n = 610), we tested differences in the five
year trend of HbA1C and SBP according to comorbidity profiles. In a mixed model
analysis technique we corrected for relevant covariates. Influence of comorbidity
(a chronic disease already present when diabetes was diagnosed) was tested as
total number of comorbid diseases, and as presence of specific disease groups,
i.e. cardiovascular, mental, and musculoskeletal disease, malignancies, and COPD.
In subgroup effect analyses we tested if potential differences were modified by
age, sex, socioeconomic status, and BMI. RESULTS: The number of comorbid diseases
significantly influenced the SBP trend, with highest values after five years for
diabetes patients without comorbidity (p = 0.005). The number of diseases did not
influence the HbA1C trend (p = 0.075). Comorbid musculoskeletal disease resulted
in lower HbA1C at the time of diabetes diagnosis, but in higher values after five
years (p = 0.044). Patients with cardiovascular diseases had sustained elevated
levels of SBP (p = 0.014). Effect modification by socioeconomic status was
observed in some comorbidity subgroups. CONCLUSIONS: Presence of comorbidity in
type 2 diabetes patients affected the long-term course of HbA1C and SBP in this
primary care cohort. Numbers and types of comorbidity showed differential
effects: not the simple sum of diseases, but specific types of comorbid disease
had a negative influence on long-term diabetes control parameters. The complex
interactions between comorbidity, diabetes control and effect modifiers require
further investigation and may help to personalize treatment goals.
PMID- 26426906
TI - Comparison of high-intensity sound and mechanical vibration for cleaning porous
titanium cylinders fabricated using selective laser melting.
AB - Orthopedic components, such as the acetabular cup in total hip joint replacement,
can be fabricated using porous metals, such as titanium, and a number of
processes, such as selective laser melting. The issue of how to effectively
remove loose powder from the pores (residual powder) of such components has not
been addressed in the literature. In this work, we investigated the feasibility
of two processes, acoustic cleaning using high-intensity sound inside acoustic
horns and mechanical vibration, to remove residual titanium powder from selective
laser melting-fabricated cylinders. With acoustic cleaning, the amount of
residual powder removed was not influenced by either the fundamental frequency of
the horn used (75 vs. 230 Hz) or, for a given horn, the number of soundings
(between 1 and 20). With mechanical vibration, the amount of residual powder
removed was not influenced by the application time (10 vs. 20 s). Acoustic
cleaning was found to be more reliable and effective in removal of residual
powder than cleaning with mechanical vibration. It is concluded that acoustic
cleaning using high-intensity sound has significant potential for use in the
final preparation stages of porous metal orthopedic components. (c) 2015 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 117-123, 2017.
PMID- 26426907
TI - Understanding the rates of nonpolar organic chemical accumulation into passive
samplers deployed in the environment: Guidance for passive sampler deployments.
AB - Polymeric passive samplers have become a common method for estimating freely
dissolved concentrations in environmental media. However, this approach has not
yet been adopted by investigators conducting remedial investigations of
contaminated environmental sites. Successful adoption of this sampling
methodology relies on an understanding of how passive samplers accumulate
chemical mass as well as developing guidance for the design and deployment of
passive samplers. Herein, we outline the development of a simple mathematical
relationship of the environmental, polymer, and chemical properties that control
the uptake rate. This relationship, called a timescale, is then used to
illustrate how each property controls the rate of equilibration in samplers
deployed in the water or in the sediment. Guidance is also given on how to use
the timescales to select an appropriate polymer, deployment time, and suite of
performance reference compounds. Integr Environ Assess Manag 2016;12:486-492. (c)
2015 SETAC.
PMID- 26426910
TI - Telomere measurement in individuals occupationally exposed to pesticide mixtures
in tobacco fields.
AB - Occupational exposure to pesticides in tobacco fields causes genetic damage in
farmers. The aim of this study was to analyze tobacco farmers chronically exposed
to low doses of pesticides and nicotine (present in the tobacco leaves) in
relation to absolute telomere length (aTL), and explore the influence of
lifestyle characteristics, oxidative stress, and inorganic element levels. DNA
was isolated from peripheral blood samples from agricultural workers and non
exposed individuals, and aTL was measured by quantitative real time polymerase
chain reaction (qPCR) analysis. Oxidative stress (thiobarbituric acid reactive
substances [TBARS], which measures oxidative damage to lipids; and toxic
equivalent antioxidant capacity [TEAC], which measures total equivalent
antioxidant capacity) was evaluated in serum, and inorganic element content was
analyzed in whole blood through particle-induced X-ray emission technique. It was
found that exposure to pesticides and tobacco smoking had significant effects on
aTL. Individuals occupationally exposed to complex mixtures of pesticides in
tobacco fields and individuals who smoked had decreased aTL compared with the non
exposed group. TBARS and TEAC were significantly elevated in the exposed group.
There were no significant differences in inorganic elements. There was no
evidence of an influence of age, gender, consumption of alcoholic beverages, or
intake of fruits and vegetables on aTL within the groups. In addition, years of
work in the tobacco field in the exposed group did not influence any of the
variables analyzed. Although further studies were needed, these results suggested
differences in telomere maintenance in tobacco farmers compared with the control
group, indicating that telomere length may be a good biomarker of occupational
exposure.
PMID- 26426911
TI - Depression and distress in caregivers of children with brain tumors undergoing
treatment: psychosocial factors as moderators.
AB - OBJECTIVE: This study's objectives were to examine the effects of depression on
the distress of caregivers of children with brain tumors and to identify the
factors moderating depression and caregiver distress. METHODS: Participants were
82 caregivers of children with brain tumors undergoing treatment in the National
Cancer Center of South Korea. The depression subscale of the Symptom Checklist 90
Revised (SCL-90-R) and the Burden of a Primary Caregiver (BPC) Scale were used to
measure participants' depression and caregiver distress, respectively. The Korean
version of the Parenting Sense of Competence (K-PSOC) Scale, Family Environmental
Scale-Revised (K-FES-R), and the DUKE-UNC Functional Social Support Questionnaire
S (DUKE-UNC-FSSQ) were used to assess parental efficacy, family relationships,
and perceived social support, respectively. RESULTS: Younger patient age, lower
family income, and caregivers' greater number of years of education significantly
predicted caregiver distress. Caregivers with depression experienced
significantly more distress than those without depression. The interaction of
depression with parenting efficacy and social support affected caregiver
distress. For highly depressed caregivers, parental efficacy, social support, and
family relationships played weaker roles as protective factors against caregiver
distress. High parental efficacy and social support were protective factors
against distress in caregivers without depression. CONCLUSIONS: A multi
dimensional assessment of the psychosocial factors that may affect caregivers of
children with brain tumors should precede interventions for distress management.
Interventions tailored to individuals' psychosocial factors are needed.
PMID- 26426914
TI - Noise masking of White's illusion exposes the weakness of current spatial
filtering models of lightness perception.
AB - Spatial filtering models are currently a widely accepted mechanistic account of
human lightness perception. Their popularity can be ascribed to two reasons: They
correctly predict how human observers perceive a variety of lightness illusions,
and the processing steps involved in the models bear an apparent resemblance with
known physiological mechanisms at early stages of visual processing. Here, we
tested the adequacy of these models by probing their response to stimuli that
have been modified by adding narrowband noise. Psychophysically, it has been
shown that noise in the range of one to five cycles per degree (cpd) can
drastically reduce the strength of some lightness phenomena, while noise outside
this range has little or no effect on perceived lightness. Choosing White's
illusion (White, 1979) as a test case, we replicated and extended the
psychophysical results, and found that none of the spatial filtering models
tested was able to reproduce the spatial frequency specific effect of narrowband
noise. We discuss the reasons for failure for each model individually, but we
argue that the failure is indicative of the general inadequacy of this class of
spatial filtering models. Given the present evidence we do not believe that
spatial filtering models capture the mechanisms that are responsible for
producing many of the lightness phenomena observed in human perception. Instead
we think that our findings support the idea that low-level contributions to
perceived lightness are primarily determined by the luminance contrast at surface
boundaries.
PMID- 26426912
TI - Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to
Abnormal Enamel Formation.
AB - Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a
restrictive distribution so far demonstrated mainly in the kidney. Here, we
demonstrate the expression of CLDN16 also in the tooth germ and show that claudin
16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5
studied patients with familial hypomagnesemia with hypercalciuria and
nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation,
we studied a murine model of FHHNC and showed that CLDN16 deficiency led to
altered secretory ameloblast TJ structure, lowering of extracellular pH in the
forming enamel matrix, and abnormal enamel matrix protein processing, resulting
in an enamel phenotype closely resembling human AI. This study unravels an
association of FHHNC owing to CLDN16 mutations with AI, which is directly related
to the loss of function of CLDN16 during amelogenesis. Overall, this study
indicates for the first time the importance of a TJ protein in tooth formation
and underlines the need to establish a specific dental follow-up for these
patients.
PMID- 26426913
TI - Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease
Is Not Associated with the Proportion of Exhausted CD8+ T Cells.
AB - CD8+ T cell-restricted immunity is important in the control of HIV-1 infection,
but continued immune activation results in CD8+ T cell dysfunction. Early
initiation of antiretroviral treatment (ART) and the duration of ART have been
associated with immune reconstitution. Here, we evaluated whether restoration of
CD8+ T cell function in HIV-1-infected individuals was dependent on early
initiation of ART. HIV-specific CD107a, IFNgamma, IL-2, TNFalpha and MIP-1beta
expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4
and CD160 were measured by flow cytometry. The frequency of CD8+ T cells
expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated
individuals compared with ART-naive individuals and similar to the frequency in
HIV-uninfected controls. The expression of the three markers was similarly
independent of when therapy was initiated. Individuals treated before
seroconversion displayed an HIV-specific CD8+ T cell response that included all
five functional markers; this was not observed in individuals treated after
seroconversion or in ART-naive individuals. In summary, ART appears to restore
the total CD8+ T cell population to a less exhausted phenotype, independent of
the time point of initiation. However, to preserve multifunctional, HIV-1
specific CD8+ T cells, ART might have to be initiated before seroconversion.
PMID- 26426915
TI - Comparison of stimulus rivalry to binocular rivalry with functional magnetic
resonance imaging.
AB - When incompatible images are presented to each eye, a phenomenon known as
binocular rivalry occurs in which the viewer's conscious visual perception
alternates between the two images. In stimulus rivalry, similar perceptual
alternations between rival images can occur even in the midst of fast image
swapping between the eyes. Here, we used functional magnetic resonance imaging to
directly compare brain activity underlying the two types of perceptual rivalry.
Overall, we found that activity for binocular rivalry was always stronger and
more widespread than that for stimulus rivalry-even more so during passive
viewing conditions. In particular, the right superior parietal cortex and the
right temporoparietal junction were prominently engaged for passive binocular
rivalry. While both types of rivalry engaged higher tier visual regions such as
the ventral temporal cortex during an active task, activity for stimulus rivalry
was comparatively weak in early visual areas V1 to V3, presumably due to a weaker
feed-forward signal due to both intraocular and interocular inhibition that may
reduce effective contrast. In sum, only binocular rivalry produced perceptually
vivid alternations, increased activation of the early visual cortex, and the
coordinated engagement of dorsal stream regions, even when a task was not
performed. These findings help characterize how stimulus rivalry fits within
hierarchical models of binocular rivalry.
PMID- 26426916
TI - Invasive Squamous Cell Carcinoma With Clear Cell Change of the Eyelid Arising in
a Seborrheic Keratosis.
PMID- 26426918
TI - New Tricks for Leukocytes: Memory Where You Least Suspect It.
PMID- 26426919
TI - Quantification of mRNA Expression by RT-qPCR.
PMID- 26426920
TI - Jean-Francoise Borel and the Origin of the World's First Billion Dollar Molecule.
PMID- 26426921
TI - Use of Oxygen Carriers to Promote Islet Engraftment in Extravascular Sites.
PMID- 26426922
TI - Living Unrelated Kidney Transplantation: Trust, But Verify!
PMID- 26426923
TI - A Primer of Neoclassical (Traditional) and Behavioral Economic Principles for
Organ Transplantation: Part 1.
PMID- 26426924
TI - Cotransplantation of Polymerized Hemoglobin Reduces beta-Cell Hypoxia and
Improves beta-Cell Function in Intramuscular Islet Grafts.
AB - BACKGROUND: Muscle is a promising alternative site for islet transplantation that
facilitates rapid restoration of islet vascularization. However, the development
of fibrosis suggests massive cellular death after transplantation. This study
tested the hypothesis that islet graft function is limited by hypoxia-related
death early after intramuscular transplantation, but that this can be overcome by
cotransplantation of an oxygen carrier, that is, polymerized bovine hemoglobin
(PolyHb). METHODS: Two hundred islets were transplanted with or without different
doses of PolyHb intramuscularly to nondiabetic C57BL/6 and diabetic C57BL/6 nu/nu
mice. beta-cell hypoxia and apoptosis were evaluated by immunohistochemistry
after injection of the biochemical marker pimonidazole or by staining for caspase
3, respectively. Blood glucose concentrations were monitored for 30 days after
islet transplantation and animals were then subjected to an intravenous glucose
tolerance test. RESULTS: Substantial hypoxia was observed in control islet grafts
during the first 4 days after transplantation. Cotransplantation of PolyHb
resulted in a dose-dependent reduction of beta-cell hypoxia, but beta-cell
apoptosis was only reduced by cotransplantation of low-dose PolyHb (0.03 mg/g
body weight) due to the inflammatory effects of higher PolyHb concentrations.
Cotransplantation of low-dose PolyHb resulted in improved islet graft function 30
days after transplantation in diabetic mice, with a glucose tolerance comparable
to transplantation of 50% more islets. CONCLUSION: We conclude that
cotransplantation of islets with PolyHb can be used to effectively bridge the
critical hypoxic phase immediately after transplantation, improve islet graft
function, and reduce the number of islets needed for successful intramuscular
transplantation.
PMID- 26426925
TI - Response to Kidney Transplantation Threshold in Patients With Hepatitis C: A
Decision Analysis Model.
PMID- 26426927
TI - Outcomes of Kidney Transplant Recipients From Donation After Circulatory Death
Donors Without Preagonal Heparin Administration.
PMID- 26426926
TI - Preoperative Assessment of Renal Transplant Ureteric Blood Supply Using Ex Vivo
Normothermic Perfusion.
PMID- 26426928
TI - Cold Denaturation Unveiled: Molecular Mechanism of the Asymmetric Unfolding of
Yeast Frataxin.
AB - What is the mechanism that determines the denaturation of proteins at low
temperatures, which is, by now, recognized as a fundamental property of all
proteins? We present experimental evidence that clarifies the role of specific
interactions that favor the entrance of water into the hydrophobic core, a
mechanism originally proposed by Privalov but never proved experimentally. By
using a combination of molecular dynamics simulation, molecular biology, and
biophysics, we identified a cluster of negatively charged residues that
represents a preferential gate for the entrance of water molecules into the core.
Even single-residue mutations in this cluster, from acidic to neutral residues,
affect cold denaturation much more than heat denaturation, suppressing cold
denaturation at temperatures above zero degrees. The molecular mechanism of the
cold denaturation of yeast frataxin is intrinsically different from that of heat
denaturation.
PMID- 26426929
TI - Robust Eye Center Localization through Face Alignment and Invariant Isocentric
Patterns.
AB - The localization of eye centers is a very useful cue for numerous applications
like face recognition, facial expression recognition, and the early screening of
neurological pathologies. Several methods relying on available light for accurate
eye-center localization have been exploited. However, despite the considerable
improvements that eye-center localization systems have undergone in recent years,
only few of these developments deal with the challenges posed by the profile (non
frontal face). In this paper, we first use the explicit shape regression method
to obtain the rough location of the eye centers. Because this method extracts
global information from the human face, it is robust against any changes in the
eye region. We exploit this robustness and utilize it as a constraint. To locate
the eye centers accurately, we employ isophote curvature features, the accuracy
of which has been demonstrated in a previous study. By applying these features,
we obtain a series of eye-center locations which are candidates for the actual
position of the eye-center. Among these locations, the estimated locations which
minimize the reconstruction error between the two methods mentioned above are
taken as the closest approximation for the eye centers locations. Therefore, we
combine explicit shape regression and isophote curvature feature analysis to
achieve robustness and accuracy, respectively. In practical experiments, we use
BioID and FERET datasets to test our approach to obtaining an accurate eye-center
location while retaining robustness against changes in scale and pose. In
addition, we apply our method to non-frontal faces to test its robustness and
accuracy, which are essential in gaze estimation but have seldom been mentioned
in previous works. Through extensive experimentation, we show that the proposed
method can achieve a significant improvement in accuracy and robustness over
state-of-the-art techniques, with our method ranking second in terms of accuracy.
According to our implementation on a PC with a Xeon 2.5Ghz CPU, the frame rate of
the eye tracking process can achieve 38 Hz.
PMID- 26426930
TI - Side-Chain Engineering for Enhancing the Thermal Stability of Polymer Solar
Cells.
AB - An effective strategy of engineering side chains is proposed for enhancing solar
cell-device thermal stability. As the conjugated length of the side chains
increases, the morphological stability of the blend film is enhanced. The thermal
stability of corresponding devices is consequently improved.
PMID- 26426931
TI - Au nanoflower-Ag nanoparticle assembled SERS-active substrates for sensitive MC
LR detection.
AB - Surface-enhanced Raman scattering (SERS)-active substrates assembled by two types
of metallic nanoparticles (NPs) were fabricated. Aptamers driven Au nanoflower
(Au NF)-Ag NP core-satellite assemblies exhibited amplified SERS signals and
achieved the sensitive detection of microcystin-LR (MC-LR) in Tai lake water with
the limit of detection (LOD) of 8.6 +/- 0.4 pM.
PMID- 26426932
TI - Short-time dynamics in dispersions with competing short-range attraction and long
range repulsion.
AB - Dynamic clustering of globular Brownian particles in dispersions exhibiting
competing short-range attraction and long-range repulsion (SALR) such as low
salinity protein solutions has gained a lot of interest over the past few years.
While the structure of the various cluster phases has been intensely explored,
little is known about the dynamics of SALR systems. We present the first
systematic theoretical study of short-time diffusion and rheological transport
properties of two-Yukawa potential SALR systems in the single-particle dominated
dispersed-fluid phase, using semi-analytic methods where the salient hydrodynamic
interactions are accounted for. We show that the dynamics has unusual features
compared to reference systems with pure repulsion or attraction. Results are
discussed for the hydrodynamic function characterizing short-time diffusion that
reveals an intermediate-range-order (cluster) peak, self-diffusion and
sedimentation coefficients, and high-frequency viscosity. As important
applications, we discuss the applicability of two generalized Stokes-Einstein
relations, and assess the wavenumber range required for the determination of self
diffusion in a dynamic scattering experiment.
PMID- 26426934
TI - Dynamics of ultrathin gold layers on vitreous silica probed by density functional
theory.
AB - The structure and properties of Au ultrathin films on hydroxyl-free and
hydroxylated silica glass surfaces are investigated using ab initio molecular
dynamics simulations. Substantial surface structure dependence of Au
agglomeration behavior (solid-state dewetting) is found. On hydroxyl-free
surfaces, the Au film virtually undergoes instantaneous agglomeration accompanied
by the formation of voids exposing a bare silica glass surface. In contrast,
simulated annealing of the Au film on hydroxylated surface models leaves its
structure unchanged within the simulation time. This points to a key role of
reactive defect sites in the kinetics of solid-state dewetting processes of
metals deposited on the glass surface. Such sites are important for initial void
nucleation and formation of metal clusters. In addition, our calculations
demonstrate the crucial role of the appropriate inclusion of dispersion
interactions in density functional theory simulations of metals deposited on
glass surfaces. For defective, hydroxyl-free glass surfaces the dispersion
correction accounts for 35% of the total adhesion energy. The effect is even more
dramatic for hydroxylated glass surfaces, where adhesion energies are almost
entirely due to dispersion interactions. The Au adhesion energies of 200 and 160
kJ (mol nm(2))(-1) calculated for hydroxylated glass surfaces are in good
agreement with the experimental data.
PMID- 26426933
TI - Synthesis, Biological Evaluation, and Molecular Docking of (R)-2-((8-(3
aminopiperidin-1-yl)-3-methyl-7-(3-methylbut-2-en-1-yl)-2,6-dioxo-2,3,6,7
tetrahydro-1H-purin-1-yl)methyl)benzonitrile as Dipeptidyl Peptidase IV
Inhibitors.
AB - Type 2 diabetes (T2D) is classified as a major metabolic disorder, which has
affected approximately 194 million people worldwide. DPP-IV inhibitors as a new
therapy have shown several advantages over traditional antidiabetic drugs. Based
on the similar binding modes of Alogliptin and Linagliptin, molecular operation
was conducted via combining pharmacophore hybridization with structural
optimization between the two market drugs and racemic compounds 40 and 43 were
reported as DPP-IV inhibitors in our previous studies. But the majority of DPP-IV
inhibitors have developed into a small molecule with certain conformation; in
this study, we described the synthesis, biological evaluation, and molecular
docking of corresponding enantiomers of compounds 40 and 43. The most potent
inhibitor is (R)-40 (IC50 = 23.5 nm, F = 74.67%, T1/2 = 4 h), which exhibited
moderate antihyperglycemic activity as compared to the standard antidiabetic drug
Linagliptin in OGTT. In addition, compound (R)-40 effectively improved the
pathological state of DIO mice. Molecular docking studies clarified the favorable
binding affinity between compound (R)-40 and DPP-IV active site. Thus, compound
(R)-40 would be entitled to further development as a drug candidate on the basis
of the suitable pharmacokinetic (PK) and desirable pharmacodynamic (PD) profiles.
PMID- 26426935
TI - Expression of amelogenin and effects of cyclosporin A in developing hair
follicles in rats.
AB - Amelogenin, an enamel matrix protein has been considered to be exclusively
expressed by ameloblasts during odontogenesis. However, burgeoning evidence
indicates that amelogenin is also expressed in non-mineralizing tissues. Under
the hypothesis that amelogenin may be a functional molecule in developing hair
follicles which share developmental features with odontogenesis, this study for
the first time elucidated the presence and functional changes of amelogenin and
its receptors during rat hair follicle development. Amelogenin was specifically
localized in the outer epithelial root sheath of hair follicles. Its expression
appeared in the deeper portion of hair follicles, i.e. the bulbar and suprabulbar
regions rather than the superficial region. Lamp-1, an amelogenin receptor, was
localized in either follicular cells or outer epithelial sheath cells, reflecting
functional changes during development. The expression of amelogenin splicing
variants increased in a time-dependent manner during postnatal development of
hair follicles. Amelogenin expression was increased by treatment with cyclosporin
A, which is an inducer of anagen in the hair follicle, whereas the level of Lamp
1 and -2 was decreased by cyclosporin A treatment. These results suggest that
amelogenin may be a functional molecule involved in the development of the hair
follicle rather than an inert hair shaft matrix protein.
PMID- 26426936
TI - The Mosaic of Rottlerin.
AB - The first total synthesis of rottlerin is described. The methodology allows the
development of potential novel protein kinase C delta (PKCdelta) analogues for
better treatment of various diseases. Kamalachalcone A and dimeric rottlerin were
synthesized in a very practical and economical way using FeCl3 as a catalyst.
PMID- 26426937
TI - Modeling Our Way to Better Outcomes.
PMID- 26426938
TI - Protein expression in dairy cows with and without subclinical hypocalcaemia.
AB - AIM: To determine differences in plasma proteomic profiles between healthy cows
and those with subclinical hypocalcaemia within 12 hours after calving, and
thereby explore the underlying biological mechanism of subclinical hypocalcaemia
in dairy cows. METHODS: Plasma samples were collected within 6 hours of calving
from Holstein cows on a farm in Heilongjiang, China; 32 with subclinical
hypocalcaemia (plasma calcium concentration 1.38-2.00 mmol/L and no clinical
signs) and 59 control cows (plasma calcium concentration 2.10-2.8 mmol/L). Plasma
samples were applied to weak cationic exchange protein chips for protein
profiling by surface-enhanced laser desorption/ionisation time-of-flight mass
spectrometry (SELDI-TOF-MS), and the data were analysed using the PBS-IIC system.
The amplitude of peaks for the two groups were compared using the Wilcoxon sum
rank test, and the mass-to-charge ratio of the peaks that differed was used to
identify peptide fragments using the Swiss-Prot protein database. RESULTS: Seven
peaks were identified in the subclinical hypocalcaemia group that differed from
those of the control group (p<0.001), that represented six unique proteins.
Expression of serum albumin, fibrinogen alpha chain, amyloid beta A4 proteins and
neurosecretory protein VGF were increased, and expression of apolipoprotein A-II
and serum amyloid A proteins were decreased in the subclinical hypocalcaemic cows
compared with control cows. CONCLUSION: Use of SELDI-TOF-MS technology can
effectively identify differences in plasma protein expression patterns in cows
with subclinical hypocalcaemia. Neurosecretory protein VGF and amyloid beta A4
protein might represent useful biomarkers for diagnosis of subclinical
hypocalcaemia.
PMID- 26426939
TI - Traffic Noise and Adverse Birth Outcomes in Madrid: A Time-series Analysis.
PMID- 26426940
TI - Re: The Quasi-cohort Approach in Pharmaco epidemiology: Upgrading the Nested Case
control.
PMID- 26426941
TI - A New Technique for Evaluating Land-use Regression Models and Their Impact on
Health Effect Estimates.
AB - BACKGROUND: Leave-one-out cross-validation that fails to account for variable
selection does not properly reflect prediction accuracy when the number of
training sites is small. The impact on health effect estimates has rarely been
studied. The objective of this study was to develop an improved validation
procedure for land-use regression models with variable selection and investigate
health effect estimates in relation to land-use regression model performance.
METHODS: We randomly generated 10 training and test sets for nitrogen dioxide and
particulate matter. For each training set, we developed models and evaluated them
using a cross-holdout validation approach. Cross-holdout validation develops new
models for each evaluation compared with refitting the model without variable
selection, as in standard leave-one-out cross-validation. We also implemented
holdout validation, which evaluates model predictions using independent test
sets. We evaluated the relationship between cross-holdout validation and holdout
validation R and estimates of the association between air pollution and forced
vital capacity in the Dutch birth cohort. RESULTS: Cross-holdout validation Rs
were generally identical to holdout validation Rs, but were notably smaller than
leave-one-out cross-validation Rs. Decreases in forced vital capacity in relation
to air pollution exposure were larger for land-use regression models that had
larger holdout validation and cross-holdout validation Rs rather than leave-one
out cross-validation R. CONCLUSION: Cross-holdout validation accurately reflects
predictive ability of land-use regression models and is a useful validation
approach for small datasets. Land-use regression predictive ability in terms of
holdout validation and cross-holdout validation rather than leave-one-out cross
validation was associated with the magnitude of health effect estimates in a case
study.
PMID- 26426942
TI - Air Pollution and Cognitive Development at Age 7 in a Prospective Italian Birth
Cohort.
AB - BACKGROUND: Early life exposure to air pollution has been linked with cognitive
impairment in children, but the results have not been conclusive. We analyzed the
association between traffic-related air pollution and cognitive function in a
prospective birth cohort in Rome. METHODS: A cohort of 719 newborns was enrolled
in 2003-2004 as part of the GASPII project. At age 7 years, 474 children took the
Wechsler Intelligence Scale for Children-III to assess their cognitive
development in terms of IQ composite scores. Exposure to air pollutants (NO2,
PMcoarse, PM2.5, PM2.5 absorbance) at birth was assessed using land use
regression models. We also considered variables indicating traffic intensity. The
effect of environmental pollution on IQ was evaluated performing a linear
regression model for each outcome, adjusting for gender, child age at cognitive
test, maternal age at delivery, parental educational level, siblings, socio
economic status, maternal smoking during pregnancy, and tester. To account for
selection bias at enrollment and during follow-up, the regression models were
weighted for the inverse probabilities of participation and follow-up. RESULTS: A
10 MUg/m3 higher NO2 exposure during pregnancy was associated with 1.4 fewer
points (95% confidence interval = -2.6, -0.20) of verbal IQ, and 1.4 fewer points
(95% confidence interval = -2.7, -0.20) of verbal comprehension IQ. Similar
associations were found for traffic intensity in a 100 m buffer around home.
Other pollutants showed negative associations with larger confidence intervals.
CONCLUSIONS: Consistent with previous evidence, this study suggests an
association of exposure to NO2 and traffic intensity with the verbal area of
cognitive development.See Video Abstract at http://links.lww.com/EDE/B12.
PMID- 26426943
TI - Bias Formulas for Estimating Direct and Indirect Effects When Unmeasured
Confounding Is Present.
AB - Mediation analysis examines the influence of intermediate factors in the causal
pathway between an exposure and an outcome. It yields estimates of the direct
effect of the exposure on the outcome and of the indirect effect through the
intermediate variable. Both estimates can be biased if the relationship between
the mediator and the outcome is confounded. In this article, we study the effect
of unmeasured confounding on direct and indirect effect estimates for a
continuous mediator and an outcome that may be either binary, count, or
continuous. We formulate the effect of the confounder on the intermediate and on
the outcome directly in regression models, which makes the formulas intuitive to
use by applied users. The formulas are derived under the assumption that the
confounder follows a normal distribution. In simulations, the formulas for a
linear response model performed well, also as it did when the unmeasured
confounder was binary. For a rare binary outcome, the formulas for logistic
regression performed well if the unmeasured confounder followed a normal
distribution, but for a binary confounder the bias in the direct effect was
overcorrected. We applied the formulas to data from a case-control study (Leiden
Thrombophilia Study) on risk factors for venous thrombosis. This showed that
unmeasured confounding can severely bias the estimates of direct and indirect
effects.
PMID- 26426944
TI - Occupational Diesel Exposure, Duration of Employment, and Lung Cancer: An
Application of the Parametric G-Formula.
AB - BACKGROUND: If less healthy workers terminate employment earlier, thus
accumulating less exposure, yet remain at greater risk of the health outcome,
estimated health effects of cumulative exposure will be biased downward. If
exposure also affects termination of employment, then the bias cannot be
addressed using conventional methods. We examined these conditions as a prelude
to a reanalysis of lung cancer mortality in the Diesel Exhaust in Miners Study.
METHODS: We applied an accelerated failure time model to assess the effect of
exposures to respirable elemental carbon (a surrogate for diesel) on time to
termination of employment among nonmetal miners who ever worked underground (n =
8,307). We then applied the parametric g-formula to assess how possible
interventions setting respirable elemental carbon exposure limits would have
changed lifetime risk of lung cancer, adjusting for time-varying employment
status. RESULTS: Median time to termination was 36% shorter (95% confidence
interval = 33%, 39%), per interquartile range width increase in respirable
elemental carbon exposure. Lung cancer risk decreased with more stringent
interventions, with a risk ratio of 0.8 (95% confidence interval = 0.5, 1.1)
comparing a limit of <=25 ug/m respirable elemental carbon to no intervention.
The fraction of cases attributable to diesel exposure was 27% in this population.
CONCLUSIONS: The g-formula controlled for time-varying confounding by employment
status, the signature of healthy worker survivor bias, which was also affected by
diesel exposure. It also offers an alternative approach to risk assessment for
estimating excess cumulative risk, and the impact of interventions based entirely
on an observed population.
PMID- 26426945
TI - Unconventional Natural Gas Development and Birth Outcomes in Pennsylvania, USA.
AB - BACKGROUND: Unconventional natural gas development has expanded rapidly. In
Pennsylvania, the number of producing wells increased from 0 in 2005 to 3,689 in
2013. Few publications have focused on unconventional natural gas development and
birth outcomes. METHODS: We performed a retrospective cohort study using
electronic health record data on 9,384 mothers linked to 10,946 neonates in the
Geisinger Health System from January 2009 to January 2013. We estimated
cumulative exposure to unconventional natural gas development activity with an
inverse-distance squared model that incorporated distance to the mother's home;
dates and durations of well pad development, drilling, and hydraulic fracturing;
and production volume during the pregnancy. We used multilevel linear and
logistic regression models to examine associations between activity index
quartile and term birth weight, preterm birth, low 5-minute Apgar score and small
size for gestational age birth, while controlling for potential confounding
variables. RESULTS: In adjusted models, there was an association between
unconventional natural gas development activity and preterm birth that increased
across quartiles, with a fourth quartile odds ratio of 1.4 (95% confidence
interval = 1.0, 1.9). There were no associations of activity with Apgar score,
small for gestational age birth, or term birth weight (after adjustment for
year). In a posthoc analysis, there was an association with physician-recorded
high-risk pregnancy identified from the problem list (fourth vs. first quartile,
1.3 [95% confidence interval = 1.1, 1.7]). CONCLUSION: Prenatal residential
exposure to unconventional natural gas development activity was associated with
two pregnancy outcomes, adding to evidence that unconventional natural gas
development may impact health.See Video Abstract at http://links.lww.com/EDE/B14.
PMID- 26426946
TI - Prevalence of oesophageal epidermoid metaplasia in 1048 consecutive patients and
58 patients with squamous neoplasms.
AB - AIMS: Oesophageal epidermoid metaplasia is defined by a dense granular layer with
overlying hyperorthokeratosis, resembling the epidermis of skin. A possible
association between epidermoid metaplasia, squamous dysplasia and squamous cell
carcinoma has been proposed. The aim of this study was to compare the prevalence
of epidermoid metaplasia in patients with oesophageal squamous neoplasms with
that in a control cohort. METHODS AND RESULTS: Medical records and slides from
1048 consecutive oesophageal biopsies and resections for any indication and 58
patients with oesophageal squamous neoplasms were reviewed. Two cases (0.19%) of
epidermoid metaplasia were identified in the 1048-patient control group. The
prevalence of epidermoid metaplasia was significantly higher (P < 0.05) in the 58
patients with oesophageal squamous neoplasms, two of whom (3.5%) had concurrent
epidermoid metaplasia (odds ratio 18.1, 95% confidence interval 2.5-131). One
case was associated with a verrucous carcinoma and the other with a well
differentiated, superficial (pT1), exophytic squamous cell carcinoma. No patients
had epidermoid metaplasia in a biopsy prior to the diagnosis of squamous
neoplasia. CONCLUSIONS: The increased prevalence of epidermoid metaplasia
observed in patients with squamous neoplasms provides some additional support for
the proposed association. The hypothesis that epidermoid metaplasia is a
precursor to squamous neoplasms remains unproven.
PMID- 26426947
TI - Integrating the concept of advanced gynaecological imaging for endometriosis.
PMID- 26426948
TI - Re: New Zealand National GDM Guidelines: an alternative view of some good
practice points.
PMID- 26426949
TI - Oxygen orders differently under graphene: new superstructures on Ir(111).
AB - Using scanning tunneling microscopy, the oxygen adsorbate superstructures on bare
Ir(111) are identified and compared to the ones formed by intercalation in
between graphene and the Ir(111) substrate. For bare Ir(111) we observe O-(2 * 2)
and O-(2 * 1) structures, thereby clarifying a persistent uncertainty about the
existence of these structures and the role of defects for their stability. For
the case of graphene-covered Ir(111), oxygen intercalation superstructures can be
imaged through the graphene monolayer by choosing proper tunneling conditions.
Depending on the pressure, temperature and duration of O2 exposure as well as on
the graphene morphology, O-(2 * 2), O-(?3*?3)-R30 degrees , O-(2 * 1) and O-(2?3
* 2?3)-R30 degrees superstructures with respect to Ir(111) are observed under
the graphene cover. Two of these structures, the O-(?3 * ?3)-R30 degrees and the
(2?3 * 2?3)-R30 degrees structure are only observed when the graphene layer is
on top. Phase coexistence and formation conditions of the intercalation
structures between graphene and Ir(111) are analyzed. The experimental results
are compared to density functional theory calculations including dispersive
forces. The existence of these phases under graphene and their absence on bare
Ir(111) are discussed in terms of possible changes in the adsorbate-substrate
interaction due to the presence of the graphene cover.
PMID- 26426950
TI - Multifunctional polyoxometalates encapsulated in MIL-100(Fe): highly efficient
photocatalysts for selective transformation under visible light.
AB - H3PMo12O40 molecules have been successfully encapsulated in the cavities of MIL
100(Fe) via a facile hydrothermal method (denoted as HPMo@MIL-100(Fe)). A series
of characterization has corroborated the insertion of H3PMo12O40 within the
cavities of MIL-100(Fe). The resulting HPMo@MIL-100(Fe) nanocomposites have
exhibited much higher photoactivity than the original-MIL-100(Fe) toward the
photocatalytic selective oxidation of benzylic alcohols and the reduction of
Cr(vi) under visible light irradiation (lambda>= 420 nm). The higher
photoactivity of HPMo@MIL-100(Fe) can be attributed to the integrative effect of
enhanced light absorption intensity and more efficient separation of
photogenerated electron-hole pairs. The host porous structure of MIL-100(Fe) can
achieve a uniform composition with H3PMo12O40, which is significantly important
for producing highly reactive dispersed H3PMo12O40 molecules and enhancing the
photocatalytic activity of HPMo@MIL-100(Fe) nanocomposites. And the immobilized
H3PMo12O40 molecules are more convenient for recycling. Importantly, almost no Fe
and Mo ions leach from the MIL-100(Fe) during the reaction, which verifies the
photostability of the HPMo@MIL-100(Fe). In addition, possible photocatalytic
redox reaction mechanisms have been investigated.
PMID- 26426954
TI - Assessment of carboxyhemoglobin, hydrogen cyanide and methemoglobin in fire
victims: a novel approach.
AB - To establish the cause of death, carboxyhemoglobin (COHb), total hemoglobin
(tHb), methemoglobin (MetHb), and hydrogen cyanide (HCN) were quantified in the
blood of fire victims. We analyzed 32 out of 33 blood samples from forensic
autopsy cases in a disastrous polyurethane mattress fire, which caused the deaths
of 33 inmates at a prison in Argentina in 2006. The cadaveric blood samples were
collected by femoral vein puncture. These samples were analyzed using the IL80 CO
oximeter system for tHb, MetHb, and COHb levels and by microdiffusion for HCN and
COHb levels. Blood alcohol (ethanol) and drugs were examined by headspace gas
chromatography-flame ionization detection (HS-GC-FID) and GC-mass spectrometry
(MS), respectively. Polyurethane mattress samples were analyzed according to the
California 117 protocol. The saturation of COHb ranged from 10% to 43%, tHb from
2% to 19.7%, MetHb from 0.10% to 35.7%, and HCN from 0.24 to 15mg/L. These HCN
values are higher than the lethal levels reported in the literature. Other toxic
components routinely measured (ethanol, methanol, aldehydes, and other volatile
compounds) gave negative results in the 32 cases. Neither drugs of abuse nor
psychotropic drugs were detected. The results indicate that death in the 32 fire
victims was probably caused in part by HCN, generated during the extensive
polyurethane decomposition stimulated by a rapid increase in temperature. We also
considered the influence of oxygen depletion and the formation of other volatile
compounds such as NOx in this disaster, as well as pathological evidence
demonstrating that heat was not the cause of death in all victims. Furthermore,
statistical analysis showed that the percentage values of COHb and MetHb in the
blood were not independent variables, with chi(2)=11.12 (theoretical chi(2)=4.09,
degrees of freedom=12, and alpha=0.05). However, no correlation was found between
HCN and MetHb in the blood of the victims. This is the first report to assess the
relationship between COHb and MetHb in forensic blood samples. We further discuss
other factors that could lead to a lethal atmosphere generated by the fire and
compare the data from this disaster with that of other published fire episodes.
PMID- 26426956
TI - Two Enantiomeric Pairs of Meroterpenoids from Rhododendron capitatum.
AB - Two enantiomeric pairs of meroterpenoids, (-)- and (+)-rhodonoids A (1a and 1b)
and B (2a and 2b), were isolated unprecedentedly from partially racemic mixtures
that naturally occurred in Rhododendron capitatum. Their structures were fully
determined by spectroscopic data, X-ray crystallography, and electronic circular
dichroism analysis. Compounds 1a and 1b are the first examples of
meromonoterpenes featuring a unique 6/6/6/4 ring system. Compounds 2a and 2b
showed PTP1B inhibitory activity.
PMID- 26426957
TI - Needle-free nasal delivery of glucagon for treatment of diabetes-related severe
hypoglycemia: toxicology of polypropylene resin used in delivery device.
AB - CONTEXT: The intranasal route is a promising route of administration for several
emergency rescue drugs including naloxone and glucagon. Glucagon nasal powder
(GNP) is a novel, needle-free delivery system for intranasal administration of
glucagon for the treatment of severe hypoglycemia, an infrequent but serious
complication of insulin use in patients with diabetes. The GNP delivery device is
a compact, highly portable, single-use nasal powder dosing device constructed of
polypropylene that allows for simple, single-step administration. OBJECTIVE: To
evaluate the toxicological profile of the polypropylene resin used in the
actuator part of the delivery device that will contact skin and nasal mucosal
membranes of the patient, we performed an in vitro cytotoxicity study, a skin
sensitization study and an irritation (intracutaneous reactivity) study in animal
models. METHODS: Extracts of the actuator of the GNP device were generated from
HAM F12 medium with 10% fetal bovine serum, 0.9% sodium chloride (NaCl) or sesame
oil. The in vitro cytotoxicity test was performed in cultured L929 mouse
fibroblasts. Skin sensitization analysis was performed in 10 guinea pigs
according to the Magnusson-Kligman method, using a maximization method with
Freund's Complete Adjuvant. Irritation following intracutaneous/intradermal
treatment with device extracts (NaCl and sesame oil extractants) was assessed in
three New Zealand White rabbits. RESULTS: In vitro cytotoxicity test: Both
undiluted and diluted extract showed no toxicity (i.e. no abnormal morphology,
cell death or cell lysis) toward L929 fibroblasts (cytotoxicity grade 0).
Sensitization test in guinea pigs: Challenge with device extracts did not evoke
positive responses in test animals previously induced with device extracts. The
net response value represented an incidence rate of 0% and a net dermal
irritation score value of 0.00. Irritation (intracutaneous/intradermal) test in
New Zealand White rabbits: Device extracts and corresponding vehicle controls
caused similar irritation reactions. The difference between the mean scores for
the device extracts and the corresponding vehicle controls was less than 1.0.
CONCLUSIONS: Extracts of the polypropylene resin of the GNP delivery device are
not cytotoxic, do not result in dermal sensitization and do not cause irritation
when applied topically or intracutaneously. Given the infrequent use and very
short duration of exposure to the nasal mucosa during administration of GNP, the
polypropylene resin of the GNP device actuator will likely not cause adverse
dermal sensitization effects or irritation effects in humans and can, therefore,
be considered for use as a delivery device in clinical trials assessing the
efficacy and safety of GNP for the treatment of insulin-using patients
experiencing episodes of severe hypoglycemia.
PMID- 26426958
TI - Microbial production of scent and flavor compounds.
AB - Scents and flavors like those of fresh oranges are no longer limited to just the
natural product. Fruit, flower, and essential oil scents have found place in
cosmetics, soaps, candles, and food amongst many common household products. With
their increasing global demand and difficulty in extractation from the natural
source, alternative methods of their production are being sought. One sustainable
method is to employ microorganisms for the production of these high value
compounds. With the tools of metabolic engineering, microorganisms can be
modified to produce compounds such as esters, terpenoids, aldehydes, and methyl
ketones. Approaches and challenges for the production of these compounds from
microbial hosts are discussed in this review.
PMID- 26426959
TI - Food metabolomics: from farm to human.
AB - Metabolomics, one of the latest components in the suite of systems biology, has
been used to understand the metabolism and physiology of living systems,
including microorganisms, plants, animals and humans. Food metabolomics can be
defined as the application of metabolomics in food systems, including food
resources, food processing and diet for humans. The study of food metabolomics
has increased gradually in the recent years, because food systems are directly
related to nutrition and human health. This review describes the recent trends
and applications of metabolomics to food systems, from farm to human, including
food resource production, industrial food processing and food intake by humans.
PMID- 26426951
TI - Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology,
and Molecular Genetics of Polycystic Ovary Syndrome.
AB - Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has
both adverse reproductive and metabolic implications for affected women. However,
there is generally poor understanding of its etiology. Varying expert-based
diagnostic criteria utilize some combination of oligo-ovulation,
hyperandrogenism, and the presence of polycystic ovaries. Criteria that require
hyperandrogenism tend to identify a more severe reproductive and metabolic
phenotype. The phenotype can vary by race and ethnicity, is difficult to define
in the perimenarchal and perimenopausal period, and is exacerbated by obesity.
The pathophysiology involves abnormal gonadotropin secretion from a reduced
hypothalamic feedback response to circulating sex steroids, altered ovarian
morphology and functional changes, and disordered insulin action in a variety of
target tissues. PCOS clusters in families and both female and male relatives can
show stigmata of the syndrome, including metabolic abnormalities. Genome-wide
association studies have identified a number of candidate regions, although their
role in contributing to PCOS is still largely unknown.
PMID- 26426960
TI - Objective measurements of excess skin in post bariatric patients--inter-rater
reliability.
AB - BACKGROUND: An ability to reliably assess excess skin after massive weight loss
using well-described and transferrable methods is important. The aim of this
trial was to evaluate inter-rater reliability of ptosis and circumference
measurements in patients with excess skin after bariatric surgery. MATERIALS AND
METHODS: Twenty-five postbariatric patients were included in the study, and their
excess skin was measured 18 months after surgery. A protocol was designed to
measure excess skin in a standardised way. To evaluate the inter-rater
reliability in the measuring protocol, all patients were measured twice, by a
specialist nurse and a specialist physiotherapist. RESULTS: All circumference
measurements on different body parts had an ICC > 0.9, indicating high
reliability. Furthermore, all breast and abdominal ptosis measurements had high
reliability. In contrast, visual evaluation of abdominal ptosis had poor
reliability. Measurements of ptoses on different body parts had an ICC > 0.6.
There were no systematic differences between the results of the two testers,
except for measurements of the buttocks and maximal knee circumference.
CONCLUSION: The measuring protocol presented in this study has high reliability
and, therefore, represents a useful instrument to provide a consistent and
objective assessment of excess skin in the postbariatric patient.
PMID- 26426961
TI - Correction: Comparative Analysis of Label-Free and 8-Plex iTRAQ Approach for
Quantitative Tissue Proteomic Analysis.
PMID- 26426962
TI - Interplay between the virus and the ubiquitin-proteasome system: molecular
mechanism of viral pathogenesis.
AB - The ubiquitin-proteasome system (UPS) plays a central role in a wide range of
fundamental cellular functions by ensuring protein quality control and through
maintaining a critical level of important regulatory proteins. Viruses subvert or
manipulate this cellular machinery to favor viral propagation and to evade host
immune response. The UPS serves as a double-edged sword in viral pathogenesis: on
the one hand, the UPS is utilized by many viruses to maintain proper function and
level of viral proteins; while on the other hand, the UPS constitutes a host
defense mechanism to eliminate viral components. To combat this host anti-viral
machinery, viruses have evolved to employ the UPS to degrade or inactivate
cellular proteins that limit viral growth. This review will highlight our current
knowledge pertaining to the different roles for the UPS in viral pathogenesis.
PMID- 26426963
TI - Uncovering Nonconventional and Conventional Hydrogen Bonds in Oligosaccharides
through NMR Experiments and Molecular Modeling: Application to Sialyl Lewis-X.
AB - We describe the direct NMR detection of a C-H...O nonconventional hydrogen bond
(Hbond) and provide experimental and theoretical evidence for conventional Hbonds
in the pentasaccharide sialyl Lewis-X (sLe(X)-5) between 5 and 37 degrees C in
water. Extensive NMR structural studies together with molecular dynamics
simulations offer strong evidence for significant local dynamics in the Le(X)
core and for previously undetected conventional Hbonds in rapid equilibrium that
modulate structure. These NMR studies also showed temperature-dependent (1)H and
(13)C line broadening. The resulting model emerging from this study is more
complex than a simple rigid core description of Le(X)-like molecules and improves
our understanding of stabilizing interactions in glycans.
PMID- 26426964
TI - What approach should we take for the incidental finding of increased 18F-FDG
uptake foci in the colon on PET/CT?
AB - INTRODUCTION: F-Fluorodeoxyglucose (F-FDG) PET/CT represents an imaging modality
that is gaining increasingly more prominence in screening, staging, and
therapeutic monitoring of malignant diseases. An incidental focus of uptake in
different regions of the body is not an uncommon finding during PET/CT imaging.
Patients with incidental gastrointestinal tract findings comprise ~3% of the
overall patient group. The aim of the current study was to provide contributory
information in relation to the answer on the most appropriate approach in cases
with incidental colonic F-FDG uptake. PATIENTS AND METHODS: A retrospective
examination was performed on PET/CT results of 5258 patients. Of these, 152 were
recommended to undergo colonoscopy because of the presence of suspicious foci and
31 underwent colonoscopy within 60 days with biopsy from all visible lesions.
These dates were also examined. RESULTS: Of the 24 patients undergoing
colonoscopy with a suspicion of malignancy, five (20.83%) had no pathological
findings. Of the 19 (79.17%) cases with a pathological finding in endoscopy,
histopathology showed a benign lesion in five (20.83%), premalignant lesion in
seven (29.17%), and a malignant lesion in seven (29.17%). Among seven patients
undergoing colonoscopy because of a suspicion of inflammatory bowel disease, five
were free of pathological signs and two patients with pathological endoscopy
findings had nonspecific inflammation as documented by histopathological
examination. CONCLUSION: Colonoscopic and histopathological examination of the
increased foci of colonic F-FDG uptake incidentally detected at PET/CT seems to
be a plausible approach.
PMID- 26426965
TI - Methimazole discontinuation before radioiodine therapy in patients with Graves'
disease.
AB - INTRODUCTION: Although radioiodine therapy (RIT) has been used for the treatment
of hyperthyroidism for many decades, there is no consensus on the optimal time of
methimazole (MMI) discontinuation before RIT. The aim of this clinical trial is
to study the effect of three different time points of MMI discontinuation on
response to RIT. METHOD AND PATIENTS: Overall, 151 patients (18-65 years old),
with Graves' disease who were taking MMI and referred to I-131 therapy, were
consecutively assigned to one of three groups, and MMI was discontinued for 24
48, 48.1-72, and 72.1-168 h in group, 1, 2, and 3, respectively. Radioiodine
uptake was measured in all patients and the radioiodine dose was calculated
according to the Quimby formula to deliver 7.4 MBq of I-131 per gram of thyroid
weight. Response to RIT was assessed at 1, 3, 6, and 12 months after RIT.
RESULTS: A total of 102 women and 49 men were included in the study. The mean
administered dose of I-131 was 362.9+/-188.7 MBq (9.8+/-5.1 mCi) and the mean
time to response for radioiodine was 4.1+/-3.6 months. There was no significant
difference between the three groups in age, thyroid weight, anti-TPO level,
radioactive iodine uptake level, and radioiodine dose (P>0.1). Response to RIT at
1, 3, 6, and 12 months after administration was also not different between the
three groups (P>0.57). CONCLUSION: No difference was found in the response to
treatment between patients with MMI discontinuation for 24-48, 48.1-72, and 72.1
96 h before RIT. Shorter discontinuation of MMI before RIT may be preferable in
most patients. Video Abstract: http://links.lww.com/NMC/A39.
PMID- 26426966
TI - Determinants of diagnostic performance of 18F-FDG PET/CT in patients with fever
of unknown origin.
AB - OBJECTIVES: There is uncertainty about patient selection and the adequate timing
at which fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) is
indicated in the diagnostic work-up of fever of unknown origin (FUO). The aim of
this study was to determine the diagnostic performance of F-FDG PET/CT in
patients with FUO. METHODS: All consecutive patients who underwent F-FDG PET/CT
at the University Hospital Zurich because of FUO between 2006 and 2012 were
included in this retrospective, observational study. RESULTS: A total of 76
patients [70% men, median (interquartile range) age 60 (47-67) years] were
included. F-FDG PET/CT showed characteristically increased F-FDG activity in 56
patients (74%), leading to confirmation of or change in the suspected cause of
FUO in 57 and 17%, respectively. The final diagnosis after F-FDG PET/CT included
infection (21%), malignancy (22%), noninfectious inflammatory disease (12%),
others (5%), or an unknown cause (40%). The success rate, sensitivity, and
specificity of F-FDG PET/CT were 60, 77, and 31%, respectively. Sensitivity was
highest in patients with suspected malignancy (100%, 95% confidence interval 79
100%). Diagnostic performance was independent of the investigated variables other
than suspected infection as a cause of FUO (odds ratio 0.1, 95% confidence
interval 0.01-0.8, P=0.033). CONCLUSION: The diagnostic performance of F-FDG
PET/CT was significantly higher in patients with suspected malignancy causing a
FUO compared with suspected infection or noninfectious inflammatory disease.
However, it was independent of the baseline characteristics and duration of
fever. This supports the recommendation to perform F-FDG PET/CT early in the
diagnostic work-up of FUO, which may shorten disease duration and lower health
costs, particularly when infection or malignancy is suspected.
PMID- 26426967
TI - Partial volume correction and image segmentation for accurate measurement of
standardized uptake value of grey matter in the brain.
AB - OBJECTIVES: Our aim was to explore a novel quantitative method [based upon an MRI
based image segmentation that allows actual calculation of grey matter, white
matter and cerebrospinal fluid (CSF) volumes] for overcoming the difficulties
associated with conventional techniques for measuring actual metabolic activity
of the grey matter. METHODS: We included four patients with normal brain MRI and
fluorine-18 fluorodeoxyglucose (F-FDG)-PET scans (two women and two men; mean age
46+/-14 years) in this analysis. The time interval between the two scans was 0
180 days. We calculated the volumes of grey matter, white matter and CSF by using
a novel segmentation technique applied to the MRI images. We measured the mean
standardized uptake value (SUV) representing the whole metabolic activity of the
brain from the F-FDG-PET images. We also calculated the white matter SUV from the
upper transaxial slices (centrum semiovale) of the F-FDG-PET images. The whole
brain volume was calculated by summing up the volumes of the white matter, grey
matter and CSF. The global cerebral metabolic activity was calculated by
multiplying the mean SUV with total brain volume. The whole brain white matter
metabolic activity was calculated by multiplying the mean SUV for the white
matter by the white matter volume. The global cerebral metabolic activity only
reflects those of the grey matter and the white matter, whereas that of the CSF
is zero. We subtracted the global white matter metabolic activity from that of
the whole brain, resulting in the global grey matter metabolism alone. We then
divided the grey matter global metabolic activity by grey matter volume to
accurately calculate the SUV for the grey matter alone. RESULTS: The brain
volumes ranged between 1546 and 1924 ml. The mean SUV for total brain was 4.8-7.
Total metabolic burden of the brain ranged from 5565 to 9617. The mean SUV for
white matter was 2.8-4.1. On the basis of these measurements we generated the
grey matter SUV, which ranged from 8.1 to 11.3. CONCLUSION: The accurate
metabolic activity of the grey matter can be calculated using the novel
segmentation technique that we applied to MRI. By combining these quantitative
data with those generated from F-FDG-PET images we were able to calculate the
accurate metabolic activity of the grey matter. These types of measurements will
be of great value in accurate analysis of the data from patients with
neuropsychiatric disorders.
PMID- 26426968
TI - A comparison of acoustic radiation force impulse imaging and scintigraphy in the
functional evaluation of the major salivary glands.
AB - PURPOSE: This study aimed to determine the efficacy of acoustic radiation force
impulse (ARFI) imaging for the functional assessment of salivary glands by
comparing ARFI with salivary gland scintigraphy. MATERIALS AND METHODS: We
prospectively evaluated 60 parotid (P) glands and 60 submandibular (SM) glands of
30 patients using salivary gland scintigraphy and ARFI elastography. The average
pixel uptake and the excretion fraction (EF) in the P and SM glands were
determined scintigraphically. The degree of stiffness in the P and SM glands at
prelemon and postlemon stimulation periods were measured elastographically with
ARFI. Changes in the degree of stiffness of the P and SM glands were also
calculated with lemon stimulation. The scintigraphic and elastographic parameters
were then compared statistically. RESULTS: We found a moderate linear correlation
between the excretion function and the changes in the degree of stiffness of the
P and SM glands induced by lemon stimulation (P<0.001, r=0.661; P<0.001, r=0.530,
respectively). We also found a weak positive correlation between the EF and the
degree of stiffness of the P and SM glands in the prelemon stimulation period
(P=0.001, r=0.405; P<0.001, r=0.480, respectively). However, we did not find any
significant correlation between other scintigraphic and elastographic parameters.
CONCLUSION: ARFI imaging may play a role in the determination of the EF of P and
SM glands by measuring tissue elasticity changes with lemon stimulation. However,
ARFI does not seem to be a suitable substitute for scintigraphy in the evaluation
of the parenchymal function of P and SM glands.
PMID- 26426970
TI - Development of a conversion program to make SIMIND-generated SPECT data interfile
acceptable to Xeleris.
AB - The Monte Carlo code SIMIND is used in nuclear medicine for research purposes,
and also for testing the validity of various applications. Conversion of a SIMIND
generated interfile (header and image data file) is required to process the
simulated image data on a Xeleris workstation. Currently there is no conversion
program provided with SIMIND to convert its interfile, which is acceptable in any
nuclear medicine workstation. Manual editing of the header file is possible with
any standard text editor but it is time-consuming (requiring ~1 h) and stressful.
To alleviate this, we have developed a conversion program using FreeMat V4.0 (an
open source software similar to MATLAB from MathWorks). It takes an average of
0.04404 s to convert a SIMIND SPECT data interfile and make it acceptable to
Xeleris.
PMID- 26426969
TI - Consistency of metabolic tumor volume of non-small-cell lung cancer primary tumor
measured using 18F-FDG PET/CT at two different tracer uptake times.
AB - OBJECTIVES: The objective of this study was to test the hypothesis that the
metabolic tumor volume (MTV) of primary non-small-cell lung cancer is not
sensitive to differences in F-fluorodeoxyglucose (F-FDG) uptake time, and to
compare this consistency of MTV measurements with that of standardized uptake
value (SUV) and total lesion glycolysis (TLG). METHODS: Under Institutional
Review Board approval, 134 consecutive patients with histologically proven non
small-cell lung cancer underwent F-FDG PET/computed tomography scanning at about
1 h (early) and 2 h (delayed) after intravenous injection of F-FDG. MTV, SUV, and
TLG of the primary tumor were all measured. Student's t-test and Wilcoxon's
signed-rank test for paired data were used to compare MTV, SUV, and TLG between
the two scans. The intraclass correlation coefficient (ICC) was used to assess
agreement in PET parameters between the two scans and between the measurements
made by two observers. RESULTS: MTV was not significantly different (P=0.17)
between the two scans. However, SUVmax, SUVmean, SUVpeak, and TLG increased
significantly from the early to the delayed scans (P<0.0001 for all). The median
percentage change between the two scans in MTV (1.65%) was smaller than in SUVmax
(11.76%), SUVmean(10.57%), SUVpeak(13.51%), and TLG (14.34%); the ICC of MTV
(0.996) was greater than that of SUVmax (0.933), SUVmean (0.952), SUVpeak
(0.928), and TLG (0.982). Interobserver agreement between the two radiologists
was excellent for MTV, SUV, and TLG on both scans (ICC: 0.934-0.999). CONCLUSION:
MTV is not sensitive to common clinical variations in F-FDG uptake time, its
consistency is greater than that of SUVmax, SUVmean, SUVpeak, and TLG, and it has
excellent interobserver agreement.
PMID- 26426972
TI - Enhanced thermoelectric performance of carbon nanotubes at elevated temperature.
AB - The electronic and transport properties of the (10, 0) single-walled carbon
nanotube are studied by performing first-principles calculations and semi
classical Boltzmann theory. It is found that the (10, 0) tube exhibits a
considerably large Seebeck coefficient and electrical conductivity which are
highly desirable for good thermoelectric materials. Together with the lattice
thermal conductivity predicted by non-equilibrium molecular dynamics simulations,
the room temperature ZT value of the (10, 0) tube is estimated to be 0.15 for p
type carriers. Moreover, the ZT value exhibits strong temperature dependence and
can reach to 0.77 at 1000 K. Such a ZT value can be further enhanced to as high
as 1.9 by isotopic substitution and chemisorptions of hydrogen on the tube
surface.
PMID- 26426973
TI - Ca(2+) Interacts with Glu-22 of Abeta(1-42) and Phospholipid Bilayers to
Accelerate the Abeta(1-42) Aggregation Below the Critical Micelle Concentration.
AB - The amyloid cascade hypothesis links the amyloid-beta (Abeta) peptide aggregation
to neuronal cell damage and ultimately the etiology of Alzheimer's disease (AD).
Although Abeta aggregation has been known to accelerate at cell membranes, the
exact mechanism of Abeta peptide deposition and the involvement of extracellular
species are still largely unclear. Using surface plasmon resonance (SPR) and
atomic force microscopy (AFM), we demonstrate that Ca(2+) ions, in conjunction
with lipid bilayer, lower the threshold concentration for Abeta aggregation (>a
few micromolar in vitro) to physiological levels (low nanomolar). Circular
dichroism spectroscopy reveals that Ca(2+) ions and the lipid bilayer concertedly
accelerate the conformational change or misfolding of Abeta peptides. Molecular
dynamics calculation indicates that Ca(2+) is sandwiched between Glu-22 of Abeta
and the lipid phosphate group. SPR experiments conducted using an E22G mutant
confirmed the strong interaction among Ca(2+), Abeta(1-42), and the phospholipid
bilayer. With the C- and N-termini of the Abeta dimer fully exposed for the
attachment of additional Abeta molecules, fibrils formed with the Ca(2+)-anchored
Abeta nuclei appear to interact with lipid bilayers differently from those
preformed in solution. Thus, similar to the role of Ca(2+) in enriching islet
amyloid polypeptides in the pancreas of diabetic patients ( Biophys. J. 2013 ,
104 , 173 - 184 ) and the "Ca(2+) bridge" in mediating membrane interaction with
alpha-synuclein in the Parkinson's disease ( Biochemistry , 2006 , 45 , 10947 -
10956 ), the influence of Ca(2+) on the Abeta adsorption at cell membranes, which
leads to neuronal membrane damage in AD, cannot be overlooked.
PMID- 26426974
TI - Multimorbidity among registered immigrants in Norway: the role of reason for
migration and length of stay.
AB - OBJECTIVES: International migration is rapidly increasing worldwide. However, the
health status of migrants differs across groups. Information regarding health at
arrival and subsequent periodic follow-up in the host country is necessary to
develop equitable health care to immigrants. The objective of this study was to
determine the impact of the length of stay in Norway and other sociodemographic
variables on the prevalence of multimorbidity across immigrant groups (refugees,
labour immigrants, family reunification immigrants and education immigrants).
METHODS: This is a register-based study merging data from the National Population
Register and the Norwegian Health Economics Administration database.
Sociodemographic variables and multimorbidity across the immigrant groups were
compared using Persons' chi-square test and anova as appropriate. Several binary
logistic regression models were conducted. RESULTS: Multimorbidity was
significantly lower among labour immigrants (OR (95% CI) 0.23 (0.21-0.26) and
0.45 (0.40-0.50) for men and women, respectively) and education immigrants (OR
(95% CI) 0.40 (0.32-0.50) and 0.38 (0.33-0.43)) and higher among refugees (OR
(95% CI) 1.67 (1.57-1.78) and 1.83 (1.75-1.92)), compared to family reunification
immigrants. For all groups, multimorbidity doubled after a five-year stay in
Norway. Effect modifications between multimorbidity and sociodemographic
characteristics across the different reasons for migration were observed.
CONCLUSIONS: Multimorbidity was highest among refugees at arrival but increased
rapidly among labour immigrants, especially females. Health providers need to
ensure tailor-made preventive and management strategies that take into account
pre-migration and post-migration experiences for immigrants in order to address
their needs.
PMID- 26426975
TI - Direct and indirect relations between parent-child attachments, peer acceptance,
and self-esteem for preschool children.
AB - The present study aims to test Bowlby's suggestions concerning relations between
the child's attachment quality with parents and subsequently constructed models
of self-worth during early childhood. In most research on this question,
attachment with mothers is considered in relation to self-worth but the child's
attachment with fathers is not. Neither has the peer group been studied as an
influence on child self-esteem, in the context of attachment research. This study
addresses these relatively unstudied influences on child self-esteem. Attachment
security to mother and father was measured by the Attachment Behavior Q-Set at
two and half years of age. At five years of age social acceptance was measured
using two sociometric techniques, and the self-esteem with the California Child Q
Sort. Our analyses indicated that security of the attachment to father and peer
acceptance are both unique, significant predictors of the childrens' self-esteem.
The security of the attachment to mother was also related to child self-esteem
but did not emerge as a uniquely significant predictor. Peer acceptance appeared
to moderate of the effect of the security of the attachment to father on the self
esteem of children. Our results extend the relatively sparse literature relating
early attachments to self-esteem during early childhood.
PMID- 26426976
TI - Chiral phosphoric acid catalyzed oxidative kinetic resolution of cyclic secondary
amine derivatives including tetrahydroquinolines by hydrogen transfer to imines.
AB - A chiral Bronsted acid catalyzed dehydrogenative kinetic resolution of
tetrahydroquinoline derivatives, which are representative of cyclic secondary
amines, based on their hydrogen transfer to aromatic imines was efficiently
achieved with high enantioselectivities. This hydrogen transfer of
tetrahydroquinolines to imines was not driven by their aromatization to
quinolines. This dehydrogenative kinetic resolution could be also applied to the
asymmetric synthesis of various benzofused heterocycles containing secondary
amine cores.
PMID- 26426977
TI - A Dioxobilin-Type Fluorescent Chlorophyll Catabolite as a Transient Early
Intermediate of the Dioxobilin-Branch of Chlorophyll Breakdown in Arabidopsis
thaliana.
AB - Chlorophyll breakdown in higher plants occurs by the so called "PaO/phyllobilin"
path. It generates two major types of phyllobilins, the characteristic 1-formyl
19-oxobilins and the more recently discovered 1,19-dioxobilins. The hypothetical
branching point at which the original 1-formyl-19-oxobilins are transformed into
1,19-dioxobilins is still elusive. Here, we clarify this hypothetical crucial
transition on the basis of the identification of the first natural 1,19
dioxobilin-type fluorescent chlorophyll catabolite (DFCC). This transient
chlorophyll breakdown intermediate was isolated from leaf extracts of Arabidopsis
thaliana at an early stage of senescence. The fleetingly existent DFCC was then
shown to represent the direct precursor of the major nonfluorescent 1,19
dioxobilin that accumulated in fully senescent leaves.
PMID- 26426978
TI - Association between nucleos(t)ide analog and tumor recurrence in hepatitis B
virus-related hepatocellular carcinoma after radiofrequency ablation.
AB - Radiofrequency ablation (RFA) is the best choice for curative treatment of
hepatocellular carcinoma (HCC) cases not suitable for surgical intervention, but
efforts should be made to reduce the risk of tumor recurrence. We aimed to
investigate the association between nucleos(t)ide analog (NA) therapy for
hepatitis B virus (HBV) and the risk of HCC recurrence post-RFA. Using the Taiwan
National Health Insurance Research Database between July 1, 2004 and December 31,
2012, we screened 48,807 patients with newly diagnosed HBV-related HCC. We
identified 850 patients (200 patients who used NAs for more than 90 days and 650
who never used NA post-RFA) who received RFA as a potentially curative treatment
for HCC. Patients in the NA-treated cohort were randomly matched 1:2 with
patients in the untreated cohort by age, sex, cirrhosis, and the time period
between RFA and initiation of NA therapy. Finally, 133 patients were recruited in
the NA-treated group and 266 in the untreated group for analysis. Cumulative
incidences of and hazard ratios (HRs) for HCC recurrence were analyzed after
adjusting for competing mortality. The HCC recurrence rate of the NA-treated
group was significantly lower than that of the untreated group (2-year recurrence
rate: 41.8%; 95% confidence interval [CI]: 32.9-50.6 vs. 54.3%; 95% CI: 48.0
60.6; modified log-rank test: P < 0.05). In modified Cox's regression analysis,
NA therapy was independently associated with a decreased risk of HCC recurrence
(HR, 0.69; 95% CI: 0.50-0.95; P < 0.05). Multivariate stratified analyses
verified the association of NA therapy and decreased HCC recurrence in almost all
patient subgroups. CONCLUSION: NA therapy was associated with a decreased risk of
HCC recurrence among patients with HBV-related HCC post-RFA.
PMID- 26426979
TI - Hybrid 'superswarm' leads to rapid divergence and establishment of populations
during a biological invasion.
AB - Understanding the genetic background of invading species can be crucial
information clarifying why they become invasive. Intraspecific genetic admixture
among lineages separated in the native ranges may promote the rate and extent of
an invasion by substantially increasing standing genetic variation. Here, we
examined the genetic relationships among threespine stickleback that recently
colonized Switzerland. This invasion results from several distinct genetic
lineages that colonized multiple locations and have since undergone range
expansions, where they coexist and admix in parts of their range. Using 17
microsatellites genotyped for 634 individuals collected from 17 Swiss and two non
Swiss European sites, we reconstruct the invasion of stickleback and investigate
the potential and extent of admixture and hybridization among the colonizing
lineages from a population genetic perspective. Specifically, we test for an
increase in standing genetic variation in populations where multiple lineages
coexist. We find strong evidence of massive hybridization early on, followed by
what appears to be recent increased genetic isolation and the formation of
several new genetically distinguishable populations, consistent with a hybrid
'superswarm'. This massive hybridization and population formation event(s)
occurred over approximately 140 years and likely fuelled the successful invasion
of a diverse range of habitats. The implications are that multiple colonizations
coupled with hybridization can lead to the formation of new stable genetic
populations potentially kick-starting speciation and adaptive radiation over a
very short timescale.
PMID- 26426980
TI - The use of the diaphragmatico-hepatic (DH) views of the abdominal and thoracic
focused assessment with sonography for triage (AFAST/TFAST) examinations for the
detection of pericardial effusion in 24 dogs (2011-2012).
AB - OBJECTIVE: To evaluate the clinical usefulness of the diaphragmatico-hepatic (DH)
view of the abdominal and thoracic focused assessment with sonography for triage
(AFAST/TFAST) in detecting pericardial effusion (PE) in dogs. DESIGN:
Retrospective case series from 2011 to 2012. SETTING: Private practice emergency
and critical care hospital. ANIMALS: Twenty-four dogs with PE diagnosed by FAST.
INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Fifty-two medical records from
October 1, 2011 through September 30, 2012 had the terms "PE" within the medical
record. Twenty-four dogs were diagnosed with PE by FAST with entries for the DH
view. Of the 24 dogs, 7 had abdominal FAST, 6 had thoracic FAST (TFAST), and 11
had both exams performed. PE was noted on the DH view in 20 of 24 (83%) cases.
Subjective PE volume assessment ranged from trivial (<5 mm) to severe. Of the 4
cases in which PE was absent via the DH view, PE was seen during the same exam at
the TFAST pericardial views (n = 2) or detected on serial exam at the DH view (n
= 2). The PE volume that was missed via the DH view was characterized as trivial
(<5 mm; n = 1), mild (n = 1), and moderate (n = 2). CONCLUSIONS: The DH view of
FAST was found to be clinically helpful for the detection of PE. Veterinarians
should make it routine practice and part of FAST training to look into the thorax
via the DH view during both abdominal FAST and TFAST exams.
PMID- 26426983
TI - Association of serum sodium levels with all-cause and cardiovascular mortality in
chronic kidney disease: Results from a prospective observational study.
AB - AIMS: The prevalence of hyponatraemia in the outpatient setting has not been
thoroughly explored, and little is known about the prognostic implication of
dysnatraemia in chronic kidney disease (CKD) patients, in particular
accommodating the effect of concurrent medications. METHODS: This is a
prospective observational study of non-dialysis-dependent CKD patients managed in
a nephrology clinic. Patients enrolled between 2002 and 2012 in the Chronic Renal
Insufficiency Standards Implementation Study were assessed. Survival analyses
were performed using baseline sodium and 12-month time-averaged sodium, with
adjustment for co-morbid diseases, laboratory findings and concurrent
medications. RESULTS: At baseline (n = 2093), mean estimated glomerular
filtration rate was 32.8 +/- 15.9 ml/min per 1.73 m(2) , median age was 67
(interquartile range 56-75) years and median serum sodium concentration was 140
(138-142) mmol/l. After a follow up of 41 (18-67) months, there were 684 deaths,
174 from cardiovascular causes; 1925 time-averaged sodium values were analysed.
In the Cox multivariate adjusted regression, baseline hyponatraemia, but not
hypernatraemia, was independently associated with all-cause mortality (hazard
ratio (HR) 1.35, 95% confidence interval (CI) 1.02-1.78, P = 0.04, and HR 1.15,
95% CI 0.84-1.57, P = 0.39, respectively). This was similarly the case for time
averaged hyponatraemia and hypernatraemia (HR 2.15, 95% CI 1.59-2.91, P < 0.01,
and HR 1.47, 95% CI 0.93-2.38, P = 0.10, respectively). However, the association
of baseline and time-averaged hyponatraemia with cardiovascular mortality was not
significant. CONCLUSION: Hyponatraemia in the ambulatory setting is associated
with all-cause but not cardiovascular mortality in CKD, independent of
concomitant medications and co-morbidities.
PMID- 26426981
TI - Protection from Radiation-Induced Pulmonary Fibrosis by Peripheral Targeting of
Cannabinoid Receptor-1.
AB - Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic
radiotherapy that limits its dose, intensity, and duration. The contribution of
the endocannabinoid signaling system in pulmonary fibrogenesis is not known.
Using a well-established mouse model of RIF, we assessed the involvement of
cannabinoid receptor-1 (CB1) in the onset and progression of pulmonary fibrosis.
Female C57BL/6 mice and CB1 knockout mice generated on C57BL/6 background
received 20 Gy (2 Gy/min) single-dose thoracic irradiation that resulted in
pulmonary fibrosis and animal death within 15 to 18 weeks. Some C57BL/6 animals
received the CB1 peripherally restricted antagonist AM6545 at 1 mg/kg
intraperitoneally three times per week. Animal survival and parameters of
pulmonary inflammation and fibrosis were evaluated. Thoracic irradiation (20 Gy)
was associated with marked pulmonary inflammation and fibrosis in mice and high
mortality within 15 to 18 weeks after exposure. Genetic deletion or
pharmacological inhibition of CB1 receptors with a peripheral CB1 antagonist
AM6545 markedly attenuated or delayed the lung inflammation and fibrosis and
increased animal survival. Our results show that CB1 signaling plays a key
pathological role in the development of radiation-induced pulmonary inflammation
and fibrosis, and peripherally restricted CB1 antagonists may represent a novel
therapeutic approach against this devastating complication of
radiotherapy/irradiation.
PMID- 26426984
TI - Barrier function and natural moisturizing factor levels after cumulative exposure
to a fruit-derived organic acid and a detergent: different outcomes in atopic and
healthy skin and relevance for occupational contact dermatitis in the food
industry.
AB - BACKGROUND: Fruit-derived organic compounds and detergents are relevant exposure
factors for occupational contact dermatitis in the food industry. Although
individuals with atopic dermatitis (AD) are at risk for development of
occupational contact dermatitis, there have been no controlled studies on the
effects of repeated exposure to multiple irritants, relevant for the food
industry, in atopic skin. OBJECTIVES: The aim of the study was to investigate the
outcomes of repeated exposure to a fruit-derived organic acid and a detergent in
AD compared to healthy volunteers. METHODS: The volunteers were exposed to 2.0%
acetic acid (AcA) and/or 0.5% sodium lauryl sulfate (SLS) in controlled tandem
repeated irritation test. The outcomes were assessed by measurements of erythema,
transepidermal water loss (TEWL) and natural moisturizing factor (NMF) levels.
RESULTS: In the AD volunteers, repeated AcA exposure led to barrier disruption
and significant TEWL increase; no significant differences after the same exposure
in the healthy controls were found. Repeated exposure to SLS and the irritant
tandems enhanced the reactions and resulted in a significantly higher increase in
TEWL in the AD compared to the control group. Cumulative irritant exposure
reduced the NMF levels in both groups. CONCLUSIONS: Differences in the severity
of irritant-induced barrier impairment in atopic individuals contribute to the
risk for occupational contact dermatitis in result of multiple exposures to food
derived irritants and detergents.
PMID- 26426985
TI - Loss of thermal refugia near equatorial range limits.
AB - This study examines the importance of thermal refugia along the majority of the
geographical range of a key intertidal species (Patella vulgata Linnaeus, 1758)
on the Atlantic coast of Europe. We asked whether differences between sun-exposed
and shaded microhabitats were responsible for differences in physiological stress
and ecological performance and examined the availability of refugia near
equatorial range limits. Thermal differences between sun-exposed and shaded
microhabitats are consistently associated with differences in physiological
performance, and the frequency of occurrence of high temperatures is most
probably limiting the maximum population densities supported at any given place.
Topographical complexity provides thermal refugia throughout most of the
distribution range, although towards the equatorial edges the magnitude of the
amelioration provided by shaded microhabitats is largely reduced. Importantly,
the limiting effects of temperature, rather than being related to latitude, seem
to be tightly associated with microsite variability, which therefore is likely to
have profound effects on the way local populations (and consequently species)
respond to climatic changes.
PMID- 26426986
TI - Nanoscopic fuel-rich thermobaric formulations: Chemical composition optimization
and sustained secondary combustion shock wave modulation.
AB - Advanced thermobaric explosives have become one of the urgent requirements when
targeting caves, fortified structures, and bunkers. Highly metal-based systems
are designed to exploit the secondary combustion resulted from active metal
particles; thus sustained overpressure and additional thermal loadings can be
achieved. This study, reports on a novel approach for chemical composition
optimization using thermochemical calculations in an attempt to achieve the
highest explosion power. Shock wave resulted from thermobaric explosives (TBX)
was simulated using ANSYS((r)) AUTODYN((r)) 2D hydrocode. Nanoscopic fuel-rich
thermobaric charge was prepared by pressing technique; static field test was
conducted. Comparative studies of modeled pressure-time histories to practical
measurements were conducted. Good agreement between numerical modeling and
experimental measurements was observed, particularly in terms of the prediction
of wider overpressure profile which is the main characteristics of TBX. The TBX
wider overpressure profile was ascribed to the secondary shock wave resulted from
fuel combustion. The shock wave duration time and its decay pattern were
acceptably predicted. Effective lethal fire-ball duration up to 50ms was achieved
and evaluated using image analysis technique. The extended fire-ball duration was
correlated to the additional thermal loading due to active metal fuel combustion.
The tailored thermobaric charge exhibited an increase in the total impulse by 40
45% compared with reference charge.
PMID- 26426987
TI - Enrichment of adenosine using thermally responsive chromatographic materials
under friendly pH conditions.
AB - A thermally responsive boronate affinity chromatographic material, which showed
thermal sensitivity, had been successfully applied for the enrichment and
separation of cis-diol-containing compounds, and the capture and release process
could be facilitated by adjusting the temperature. However, in this system, the
pH of the mobile phase must be higher than 9.8, and alkaline media can lead to
the degradation of labile compounds; the use of silica beads also limits its use.
In this study, thermally responsive boronate affinity chromatographic material,
namely poly(N-isopropylacrylamide-co-N-acryloyl-3-aminophenylboronic acid)
grafted silica, was successfully prepared by atom transfer radical
polymerization. Its structure was confirmed by IR spectroscopy and the graft
ratio was 20.8%, determined by thermogravimetric analysis. Furthermore, the
capture/release of adenosine, a cis-diol, was performed from pH 5.0-9.0 and 10-50
degrees C. The elution of adenosine was remarkably retarded at decreased
temperatures and adenosine could be captured completely at 10 degrees C at pH
values of 5.0-9.0. The enrichment of adenosine could be achieved by simply
changing the temperature from 10 to 50 degrees C. Therefore, this material not
only improved the stability of the silica, but was also suitable for the capture
of oxidation-sensitive biological analytes. Moreover, it could be used for the
enrichment of cis-diol-containing compounds in LC with MS.
PMID- 26426989
TI - Lipids under stress--a lipidomic approach for the study of mood disorders.
AB - The emerging field of lipidomics has identified lipids as key players in disease
physiology. Their physicochemical diversity allows precise control of cell
structure and signaling events through modulation of membrane properties and
trafficking of proteins. As such, lipids are important regulators of brain
function and have been implicated in neurodegenerative and mood disorders.
Importantly, environmental chronic stress has been associated with anxiety and
depression and its exposure in rodents has been extensively used as a model to
study these diseases. With the accessibility to modern mass-spectrometry
lipidomic platforms, it is now possible to snapshot the extensively
interconnected lipid network. Here, we review the fundamentals of lipid biology
and outline a framework for the interpretation of lipidomic studies as a new
approach to study brain pathophysiology. Thus, lipid profiling provides an
exciting avenue for the identification of disease signatures with important
implications for diagnosis and treatment of mood disorders.
PMID- 26426988
TI - Control of hydroxyapatite coating by self-assembled monolayers on titanium and
improvement of osteoblast adhesion.
AB - Self-assembly technique was applied to introduce functional groups and form
hydroxyl-, amine-, and carboxyl-terminal self-assembled monolayers (SAMs). The
SAMs were grafted onto titanium substrates to obtain a molecularly smooth
functional surface. Subsequent hydrothermal crystal growth formed homogeneous and
crack-free crystalline hydroxyapatite (HA) coatings on these substrates. AFM and
XPS were used to characterize the SAM surfaces, and XRD, SEM, and TEM were used
to characterize the HA coatings. Results show that highly crystalline, dense, and
oriented HA coatings can be formed on the OH-, NH2 -, and COOH-SAM surfaces. The
SAM surface with -COOH exhibited stronger nucleating ability than that with -OH
and -NH2 . The nucleation and growth processes of HA coatings were effectively
controlled by varying reaction time, pH, and temperature. By using this method,
highly crystalline, dense, and adherent HA coatings were obtained. In addition,
in vitro cell evaluation demonstrated that HA coatings improved cell adhesion as
compared with pristine titanium substrate. The proposed method is considerably
effective in introducing the HA coatings on titanium surfaces for various
biomedical applications and further usage in other industries. (c) 2015 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 124-135, 2017.
PMID- 26426991
TI - Mindfulness, Self-Compassion, Posttraumatic Stress Disorder Symptoms, and
Functional Disability in U.S. Iraq and Afghanistan War Veterans.
AB - Mindfulness and self-compassion are overlapping, but distinct constructs that
characterize how people relate to emotional distress. Both are associated with
posttraumatic stress disorder (PTSD) and may be related to functional disability.
Although self-compassion includes mindful awareness of emotional distress, it is
a broader construct that also includes being kind and supportive to oneself and
viewing suffering as part of the shared human experience--a potentially powerful
way of dealing with distressing situations. We examined the association of
mindfulness and self-compassion with PTSD symptom severity and functional
disability in 115 trauma-exposed U.S. Iraq/Afghanistan war veterans. Mindfulness
and self-compassion were each uniquely, negatively associated with PTSD symptom
severity. After accounting for mindfulness, self-compassion accounted for unique
variance in PTSD symptom severity (f(2) = .25; medium ES). After accounting for
PTSD symptom severity, mindfulness and self-compassion were each uniquely
negatively associated with functional disability. The combined association of
mindfulness and self-compassion with disability over and above PTSD was large
(f(2) = .41). After accounting for mindfulness, self-compassion accounted for
unique variance in disability (f(2) = .13; small ES). These findings suggest that
interventions aimed at increasing mindfulness and self-compassion could
potentially decrease functional disability in returning veterans with PTSD
symptoms.
PMID- 26426992
TI - First description of a sporadic breast cancer in a woman with BRCA1 germline
mutation.
AB - We describe the case of a woman carrying a germline pathogenic BRCA1 mutation
diagnosed with a breast cancer overexpressing HER2. Clinical presentation of the
tumor, HER2-positivity, genomic profile and loss of the mutated BRCA1 allele in
tumor evidence that BRCA1 is not inactivated in this breast cancer. It represents
the first biological demonstration for the existence of a sporadic HER2-positive
breast cancer independent from BRCA loss of function in a woman carrier of a
deleterious BRCA1 mutation. In a context where targeted therapies based on BRCA
loss of function in the tumor are developed, such case could have direct
implications.
PMID- 26426971
TI - The Influence of Age and Sex on Genetic Associations with Adult Body Size and
Shape: A Large-Scale Genome-Wide Interaction Study.
AB - Genome-wide association studies (GWAS) have identified more than 100 genetic
variants contributing to BMI, a measure of body size, or waist-to-hip ratio
(adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape
change as people grow older and these changes differ substantially between men
and women. To systematically screen for age- and/or sex-specific effects of
genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies
(up to 320,485 individuals of European descent) with genome-wide chip and/or
Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT)
Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and
WHRadjBMI in four strata (men <=50y, men >50y, women <=50y, women >50y) and
summary statistics were combined in stratum-specific meta-analyses. We then
screened for variants that showed age-specific effects (G x AGE), sex-specific
effects (G x SEX) or age-specific effects that differed between men and women (G
x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main
effects, four novel) that showed significant (FDR<5%) age-specific effects, of
which 11 had larger effects in younger (<50y) than in older adults (>=50y). No
sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44
loci (27 previously established for main effects, 17 novel) with sex-specific
effects, of which 28 showed larger effects in women than in men, five showed
larger effects in men than in women, and 11 showed opposite effects between
sexes. No age-dependent effects were identified for WHRadjBMI. This is the first
genome-wide interaction meta-analysis to report convincing evidence of age
dependent genetic effects on BMI. In addition, we confirm the sex-specificity of
genetic effects on WHRadjBMI. These results may provide further insights into the
biology that underlies weight change with age or the sexually dimorphism of body
shape.
PMID- 26426993
TI - Prognosis of patients with esophageal squamous cell carcinoma after esophagectomy
using the log odds of positive lymph nodes.
AB - To compare the log odds of positive lymph nodes (LODDS) with the number of
positive lymph nodes (pN), lymph node ratio (LNR), removed lymph node (RLN)
count, and negative lymph node (NLN) count in determining the prognosis of
patients with esophageal squamous cell carcinoma (ESCC) after esophagectomy. The
records of patients with ESCC who received esophagectomy were retrospectively
reviewed. The log-rank test was used to compare curves for overall survival (OS),
and Cox regression analysis was performed to identify prognostic factors. The
prognostic performance of the different lymph node staging systems were compared
using the linear trend chi-square test, likelihood ratio chi-square test, and
Akaike information criterion. A total of 589 patients were enrolled. Univariate
Cox analysis showed that pN stage, LNR, RLN count, NLN count, and the LODDS were
significantly associated with OS (p < 0.05 for all). Multivariate Cox analysis
adjusted for significant factors indicated that LODDS was independent risk factor
on overall survival (OS), and a higher LODDS was associated with worse OS (hazard
ratio = 3.297, 95% confidence interval: 2.684-4.050, p < 0.001). The modified
Tumor-LODDS-Metastasis staging system had better discriminatory ability,
monotonicity, and homogeneity, and better optimistic prognostic stratification
than the Tumor-Node-Metastasis staging system in determining the prognosis of
patients with ESCC. The LODDS staging system was superior to other lymph node
classifications in determining the prognosis of patients with ESCC after
esophagectomy. LODDS may be incorporated into esophageal staging system if these
results are eventually confirmed by other studies.
PMID- 26426995
TI - Psychometric evaluation of novel measures of partner interfering and supportive
behaviors among women with cancer.
AB - PURPOSE: The aim of this study was to evaluate the psychometric properties of
complementary and novel measures of partner interfering and partner supportive
behaviors in cancer care (PIB-C and PSB-C). METHODS: Structured telephone
interviews were conducted with 378 women (aged 18-79) in partnered relationships
and recruited from the Kentucky Cancer Registry. Psychometric analyses of PIB-C
and PSB-C were used to determine scale reliability, and scale construct and
predictive validity (correlations with indicators of partner abuse, symptoms of
depression, anxiety, and stress after cancer). RESULTS: Cronbach's alpha and
split-half calculations indicated excellent internal consistency of the 20-item
PIB-C (0.936 and 0.87, respectively) and 12-item PSB-C (0.930 and 0.89). Three
thematic clusters for the PIB-C and two for the PSB-C were identified through
factor analyses. Regarding construct validity, higher PIB-C and lower PSB-C
scores were associated with a measure of psychological impacts from abuse.
Predictive validity was suggested through (1) lower PSB-C associated with
depression, (2) higher PIB-C associated with anxiety, and (3) higher perceived
stress associated with higher PIB-C/lower PSB-C scores. CONCLUSION: Both PIB-C
and PSB-C have strong psychometric properties and distinguish partner behaviors
more likely to negatively impact women's depression, anxiety, and stress during
cancer care/recovery. Use of these measures may assist clinical teams in
comprehensively assessing women patients' home environment to best ensure cancer
care/recovery. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26426994
TI - Repurposing the anti-malarial drug artesunate as a novel therapeutic agent for
metastatic renal cell carcinoma due to its attenuation of tumor growth,
metastasis, and angiogenesis.
AB - Despite advances in the development of molecularly targeted therapies, metastatic
renal cell carcinoma (RCC) is still incurable. Artesunate (ART), a well-known
anti-malarial drug with low toxicity, exhibits highly selective anti-tumor
actions against various tumors through generation of cytotoxic carbon-centered
free radical in the presence of free iron. However, the therapeutic efficacy of
ART against metastatic RCC has not yet been fully elucidated. In the analysis on
a dataset from The Cancer Genome Atlas (TCGA) (n = 469) and a tissue microarray
set from Samsung Medical Center (n = 119) from a cohort of patients with clear
cell RCC (ccRCC), up-regulation of transferrin receptor 1 (TfR1), which is a well
known predictive marker for ART, was correlated with the presence of distant
metastasis and an unfavorable prognosis. Moreover, ART exerted potent selective
cytotoxicity against human RCC cell lines (Caki-1, 786-O, and SN12C-GFP-SRLu2)
and sensitized these cells to sorafenib in vitro, and the extent of ART
cytotoxicity correlated with TfR1 expression. ART-mediated growth inhibition of
human RCC cell lines was shown to result from the induction of cell cycle arrest
at the G2/M phase and oncosis-like cell death. Furthermore, ART inhibited cell
clonogenicity and invasion of human RCC cells and anti-angiogenic effects in
vitro in a dose-dependent manner. Consistent with these in vitro data, anti
tumor, anti-metastatic and anti-angiogenic effects of ART were also validated in
human 786-O xenografts. Taken together, ART is a promising novel candidate for
treating human RCC, either alone or in combination with other therapies.
PMID- 26426996
TI - c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with
Colorectal Cancer.
AB - BACKGROUND: The aim of this study was to determine the incidence and
clinicopathological significance of c-MYC gene copy-number (GCN) gain in patients
with primary colorectal cancer (CRC). METHODS: The c-MYC GCN was investigated in
367 consecutive CRC patients (cohort 1) by using dual-color silver in situ
hybridization. Additionally, to evaluate regional heterogeneity, we examined CRC
tissue from 3 sites including the primary cancer, distant metastasis, and lymph
node metastasis in 152 advanced CRC patients (cohort 2). KRAS exons 2 and 3 were
investigated for mutations. RESULTS: In cohort 1, c-MYC gene amplification,
defined by a c-MYC:centromere of chromosome 8 ratio >= 2.0, was detected in 31
(8.4%) of 367 patients. A c-MYC GCN gain, defined by >= 4.0 c-MYC copies/nucleus,
was found in 63 (17.2%) patients and was associated with poor prognosis (P =
0.015). Multivariate Cox regression analysis showed that the hazard ratio for c
MYC GCN gain was 2.35 (95% confidence interval, 1.453-3.802; P < 0.001). In a
subgroup of stage II-III CRC patients, c-MYC GCN gain was significantly
associated with poor prognosis by univariate (P = 0.034) and multivariate (P =
0.040) analyses. c-MYC protein overexpression was observed in 201 (54.8%) out of
367 patients and weakly correlated with c-MYC GCN gain (rho, 0.211). In cohort 2,
the c-MYC genetic status was heterogenous in advanced CRC patients. Discordance
between GCN gain in the primary tumor and either distant or lymph-node metastasis
was 25.7% and 30.4%, respectively. A similar frequency for c-MYC GCN gain and
amplification was observed in CRC patients with both wild-type and mutated KRAS.
CONCLUSIONS: c-MYC GCN gain was an independent factor for poor prognosis in
consecutive CRC patients and in the stage II-III subgroup. Our findings indicate
that the status of c-MYC may be helpful in predicting the patients' outcome and
for managing CRC patients.
PMID- 26426998
TI - The Long-Run Socio-Economic Consequences of a Large Disaster: The 1995 Earthquake
in Kobe.
AB - We quantify the 'permanent' socio-economic impacts of the Great Hanshin-Awaji
(Kobe) earthquake in 1995 by employing a large-scale panel dataset of 1,719
cities, towns, and wards from Japan over three decades. In order to estimate the
counterfactual--i.e., the Kobe economy without the earthquake--we use the
synthetic control method. Three important empirical patterns emerge: First, the
population size and especially the average income level in Kobe have been lower
than the counterfactual level without the earthquake for over fifteen years,
indicating a permanent negative effect of the earthquake. Such a negative impact
can be found especially in the central areas which are closer to the epicenter.
Second, the surrounding areas experienced some positive permanent impacts in
spite of short-run negative effects of the earthquake. Much of this is associated
with movement of people to East Kobe, and consequent movement of jobs to the
metropolitan center of Osaka, that is located immediately to the East of Kobe.
Third, the furthest areas in the vicinity of Kobe seem to have been insulated
from the large direct and indirect impacts of the earthquake.
PMID- 26426997
TI - Genome and Phenotype Microarray Analyses of Rhodococcus sp. BCP1 and Rhodococcus
opacus R7: Genetic Determinants and Metabolic Abilities with Environmental
Relevance.
AB - In this paper comparative genome and phenotype microarray analyses of Rhodococcus
sp. BCP1 and Rhodococcus opacus R7 were performed. Rhodococcus sp. BCP1 was
selected for its ability to grow on short-chain n-alkanes and R. opacus R7 was
isolated for its ability to grow on naphthalene and on o-xylene. Results of
genome comparison, including BCP1, R7, along with other Rhodococcus reference
strains, showed that at least 30% of the genome of each strain presented unique
sequences and only 50% of the predicted proteome was shared. To associate genomic
features with metabolic capabilities of BCP1 and R7 strains, hundreds of
different growth conditions were tested through Phenotype Microarray, by using
Biolog plates and plates manually prepared with additional xenobiotic compounds.
Around one-third of the surveyed carbon sources was utilized by both strains
although R7 generally showed higher metabolic activity values compared to BCP1.
Moreover, R7 showed broader range of nitrogen and sulphur sources. Phenotype
Microarray data were combined with genomic analysis to genetically support the
metabolic features of the two strains. The genome analysis allowed to identify
some gene clusters involved in the metabolism of the main tested xenobiotic
compounds. Results show that R7 contains multiple genes for the degradation of a
large set of aromatic and PAHs compounds, while a lower variability in terms of
genes predicted to be involved in aromatic degradation was found in BCP1. This
genetic feature can be related to the strong genetic pressure exerted by the two
different environment from which the two strains were isolated. According to
this, in the BCP1 genome the smo gene cluster involved in the short-chain n
alkanes degradation, is included in one of the unique regions and it is not
conserved in the Rhodococcus strains compared in this work. Data obtained
underline the great potential of these two Rhodococcus spp. strains for
biodegradation and environmental decontamination processes.
PMID- 26426999
TI - Multimodal endoscope can quantify wide-field fluorescence detection of Barrett's
neoplasia.
AB - BACKGROUND AND STUDY AIMS: To demonstrate the clinical use of a multimodal
endoscope with a targeted fluorescently labeled peptide for quantitative
detection of Barrett's neoplasia. PATIENTS AND METHODS: We studied 50 patients
with Barrett's esophagus using a prototype multimodal endoscope with a
fluorescently labeled peptide. Co-registered fluorescence and reflectance images
were converted to ratios to correct for differences in distance and geometry over
the image field of view. The ratio images were segmented using a unique threshold
that maximized the variance between high and low intensities to localize regions
of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). RESULTS: Early
neoplasia (HGD and EAC) was identified with 94 % specificity and 96 % positive
predictive value at a threshold of 1.49. The mean results for HGD and EAC were
significantly greater than those for squamous/Barrett's esophagus and low grade
dysplasia by one-way analysis of variance (ANOVA). The receiver operator
characteristic curve for detection of early neoplasia had an area under the curve
of 0.884. No adverse events associated with the endoscope or peptide were found.
CONCLUSION: A multimodal endoscope can quantify fluorescence images from targeted
peptides to localize early Barrett's neoplasia. (ClinicalTrials.gov number
NCT01630798.).
PMID- 26427000
TI - Rarity of adenomatous polyps in ulcerative colitis and its implications for
colonic carcinogenesis.
AB - BACKGROUND AND STUDY AIMS: Despite ample research on the dysplasia to carcinoma
risk in ulcerative colitis, there are scant data on the prevalence of adenomatous
polyps in this population. METHODS: The number and histology of all polyps
detected at colonoscopies of ulcerative colitis patients aged > 50 during 2006 -
2012 were compared with similarly aged controls undergoing screening colonoscopy.
RESULTS: There were 206 patients with ulcerative colitis and 624 controls
included in the study (mean age 61.7 +/- 8.7 vs. 60.8 +/- 6.1, respectively; P =
0.15). Adenomatous polyps were detected in only 13/206 colonoscopies for
ulcerative colitis compared with 162 /624 controls (6.3 % vs. 25.9 %,
respectively; odds ratio [OR] 0.19, 95 % confidence interval [CI] 0.1 - 0.34; P <
0.0001). When also considering all prior colonoscopies performed over 7.7 +/- 4.6
years of follow-up (mean 4.1 +/- 2.9 colonoscopies/patient, range 1 - 15, total
832 colonoscopies), the risk of ever finding an adenoma in ulcerative colitis
patients was still significantly lower compared with controls (14.1 % vs. 25.9 %,
respectively; OR 0.47, 95 %CI 0.3 - 0.72; P = 0.0005). On multivariable analysis,
adenomas were positively associated with advanced age (OR 1.07/year, 95 %CI 1.03
1.1; P < 0.0001) and with increasing body mass index (BMI; OR 1.06/kg/m(2), 95
%CI 1.01 - 1.1; P = 0.01) and negatively associated with having ulcerative
colitis (OR 0.15, 95 %CI 0.09 - 0.44; P = 0.0005). Among 115 Crohn's disease
patients aged > 50 years, the rate of ever-adenomas in small-bowel Crohn's
disease was similar to the controls (P = 0.8) and not influenced by 5
aminosalicylic acid use, whereas patients with colonic Crohn's disease had a
significantly lower rate of adenomas compared with the controls (3.9 % vs. 25.9
%; P = 0.002). CONCLUSION: Unlike patients with small-bowel Crohn's disease,
patients with ulcerative colitis or with colonic Crohn's disease seldom develop
sporadic adenomatous polyps. These data may provide novel clues to a possible
role for colonic immune activation in restricting the adenoma to carcinoma
sequence while propagating the dysplasia to carcinoma pathway.
PMID- 26427001
TI - Efficacy of the endoscopic rendez-vous technique for the reconstruction of
complete esophageal disruptions.
AB - BACKGROUND AND STUDY AIMS: The rendezvous endoscopic approach, already described,
might be an interesting technique in complete esophageal obstructions (CEO).
PATIENTS AND METHODS: This retrospective report on nine patients referred because
of CEO classified patients into two groups based on length of their esophageal
disruption: the long (> 5 cm) group were three patients (esophageal stripping at
stent removal [n = 2] and caustic ingestion [n = 1]; two patients having superior
esophageal sphincter [SES] destruction); the short (< 5 cm) group were six
patients (anastomotic or post-radiotherapy). The procedures were performed under
radiographic guidance. RESULTS: All the reconstructions were successful. In four
patients, a neo-SES was created, by transillumination (n = 2) or surgery (n = 2).
The first dilation was performed by hydrostatic balloon, with additional metal
stents (n = 4) and nasogastric tubes (n = 2) used. All the patients were able to
eat after the procedure. Two delayed bleeds occurred, which were managed
endoscopically. The patients underwent a median of seven dilations (range 3 - 55)
over 8 months (2 - 32 months), with dilations ongoing in five patients, but all
able to eat normally. CONCLUSION: Endoscopic rendezvous for CEO is safe and
effective, even in patients with long disruptions and complete loss of SES.
PMID- 26427002
TI - In-class didactic versus self-directed teaching of the probe-based confocal laser
endomicroscopy (pCLE) criteria for Barrett's esophagus.
AB - BACKGROUND AND AIMS: Optimal teaching methods for disease recognition using probe
based confocal laser endomicroscopy (pCLE) have not been developed. Our aim was
to compare in-class didactic teaching vs. self-directed teaching of Barrett's
neoplasia diagnosis using pCLE. METHODS: This randomized controlled trial was
conducted at a tertiary academic center. Study participants with no prior pCLE
experience were randomized to in-class didactic (group 1) or self-directed
teaching groups (group 2). For group 1, an expert conducted a classroom teaching
session using standardized educational material. Participants in group 2 were
provided with the same material on an audio PowerPoint. After initial training,
all participants graded an initial set of 20 pCLE videos and reviewed correct
responses with the expert (group 1) or on audio PowerPoint (group 2). Finally,
all participants completed interpretations of a further 40 videos. RESULTS:
Eighteen trainees (8 medical students, 10 gastroenterology trainees) participated
in the study. Overall diagnostic accuracy for neoplasia prediction by pCLE was 77
% (95 % confidence interval [CI] 74.0 % - 79.2 %); of predictions made with high
confidence (53 %), the accuracy was 85 % (95 %CI 81.8 % - 87.8 %). The overall
accuracy and interobserver agreement was significantly higher in group 1 than in
group 2 for all predictions (80.4 % vs. 73 %; P = 0.005) and for high confidence
predictions (90 % vs. 80 %; P < 0.001). Following feedback (after the initial 20
videos), the overall accuracy improved from 73 % to 79 % (P = 0.04), mainly
driven by a significant improvement in group 1 (74 % to 84 %; P < 0.01). Accuracy
of prediction significantly improved with time in endoscopy training (72 %
students, 77 % FY1, 82 % FY2, and 85 % FY3; P = 0.003). CONCLUSION: For novice
trainees, in-class didactic teaching enables significantly better recognition of
the pCLE features of Barrett's esophagus than self-directed teaching. The in
class didactic group had a shorter learning curve and were able to achieve 90 %
accuracy for their high confidence predictions.
PMID- 26427003
TI - Gastrocnemius muscle architecture and achilles tendon properties influence
walking distance in claudicants with peripheral arterial disease.
AB - INTRODUCTION: The extent to which gastrocnemius muscle and Achilles tendon
properties contribute to the impaired walking endurance of claudicants is not
known. METHODS: Ultrasound images quantified muscle architecture of the lateral
and medial gastrocnemius (GL and GM) and were combined with dynamometry during
plantarflexor contractions to calculate tendon stress, strain, stiffness, the
Young modulus, and hysteresis. Key parameters were entered into multiple
regression models to explain walking endurance. RESULTS: Worse disease severity
was significantly associated with longer fascicle: tendon length ratios (GL R =
0.789 and GM R = -0.828) and increased tendon hysteresis (R = -0.740). Walking
endurance could be explained by GL and GM pennation angle, maximum tendon force,
tendon hysteresis, and disease severity (R(2) = ~0.6). CONCLUSIONS: Peripheral
arterial disease was associated with functionally important changes in muscle and
tendon properties, including the usage of stored elastic energy. Interventions
known to target these characteristics should be adopted as a means to improve
walking endurance.
PMID- 26427006
TI - Thermally Driven Large N-Type Voltage Responses from Hybrids of Carbon Nanotubes
and Poly(3,4-ethylenedioxythiophene) with Tetrakis(dimethylamino)ethylene.
AB - Hybrids of carbon nanotubes (CNTs) and poly(3,4-ethylenedioxythiophene) (PEDOT)
treated by tetrakis(dimethylamino)ethylene (TDAE) have large n-type voltages in
response to temperature differences. The reduced carrier concentration by TDAE
reduction and partially percolated CNT networks embedded in the PEDOT matrix
result in high thermopower and low thermal conductivity. The high electron
mobility in the CNTs helps to minimally reduce the electrical conductivity of the
hybrid, resulting in a large figure-of-merit.
PMID- 26427005
TI - De Novo Transcriptome Assembly in Firmiana danxiaensis, a Tree Species Endemic to
the Danxia Landform.
AB - Many Firmiana species are locally endemic, providing an interesting system for
studying adaptation and speciation. Among these species, F. danxiaensis is a tree
species endemic to Mount Danxia in Guangdong, China, which is an area known for
presenting the Danxia landform. How F. danxiaensis could have adapted to the
stressful environment of rocky cliffs covered with barren soils in the Danxia
landform is still unknown. In this study, we performed de novo assembly of the
transcriptome of F. danxiaensis, obtaining 47,221 unigenes with an N50 value of
987 bp. Homology analysis showed that 32,318 of the unigenes presented hits in
the NCBI non-redundant database, and 31,857 exhibited significant matches with
the protein database of Theobroma cacao. Gene Ontology (GO) annotation showed
that hundreds of unigenes participated in responses to various stresses or
nutritional starvation, which may help us to understand the adaptation of F.
danxiaensis to Danxia landform. Additionally, we found 263 genes related to
responses to Cd, partially explaining the high accumulation of Cd observed in
Firmiana species. The EuKaryotic Orthologous Groups (KOG) and Kyoto Encyclopedia
of Genes and Genomes (KEGG) annotations revealed many genes playing roles in the
biosynthesis of secondary metabolites and environmental adaptation, which may
also contribute to the survivor and success of Firmiana species in extreme
environments. Based on the obtained transcriptome, we further identified a
Firmiana-specific whole-genome duplication event that occurred approximately 20
Mya, which may have provided raw materials for the diversification of Firmiana
species.
PMID- 26427004
TI - Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and
Neurotypical Siblings in the Simons Simplex Collection.
AB - In order to assess potential associations between autism spectrum disorder (ASD)
phenotype, functional GI disorders and fecal microbiota, we recruited simplex
families, which had only a single ASD proband and neurotypical (NT) siblings,
through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN).
Fecal samples and metadata related to functional GI disorders and diet were
collected from ASD probands and NT siblings of ASD probands (age 7-14).
Functional gastrointestinal disorders (FGID) were assessed using the parent
completed ROME III questionnaire for pediatric FGIDs, and problem behaviors were
assessed using the Child Behavior Check List (CBCL). Targeted quantitative
polymerase chain reaction (qPCR) assays were conducted on selected taxa
implicated in ASD, including Sutterella spp., Bacteroidetes spp. and Prevotella
spp. Illumina sequencing of the V1V2 and the V1V3 regions of the bacterial 16S
rRNA genes from fecal DNA was performed to an average depth of 208,000 and
107,000 high-quality reads respectively. Twenty-five of 59 ASD children and 13 of
44 NT siblings met ROME III criteria for at least one FGID. Functional
constipation was more prevalent in ASD (17 of 59) compared to NT siblings (6 of
44, P = 0.035). The mean CBCL scores in NT siblings with FGID, ASD children with
FGID and ASD without FGID were comparably higher (58-62 vs. 44, P < 0.0001) when
compared to NT children without FGID. There was no significant difference in
macronutrient intake between ASD and NT siblings. There was no significant
difference in ASD severity scores between ASD children with and without FGID. No
significant difference in diversity or overall microbial composition was detected
between ASD children with NT siblings. Exploratory analysis of the 16S rRNA
sequencing data, however, identified several low abundance taxa binned at the
genus level that were associated with ASD and/or first order ASD*FGID
interactions (FDR <0.1).
PMID- 26427007
TI - Iridotomy: a brief history and some physics.
PMID- 26427008
TI - Carpe diem.
PMID- 26427010
TI - Deducing CO2 motion, adsorption locations and binding strengths in a flexible
metal-organic framework without open metal sites.
AB - Microporous metal-organic frameworks (MOFs) have high surface areas and
porosities, and are well-suited for CO2 capture. MIL-53 features corner-sharing
MO4(OH)2 (M = Al, Ga, Cr, etc.) octahedra interconnected by benzenedicarboxylate
linkers that form one-dimensional rhombic tunnels, and exhibits an excellent
adsorption ability for guest molecules such as CO2. Studying the behavior of
adsorbed CO2 in MIL-53 via solid-state NMR (SSNMR) provides rich information on
the dynamic motion of guest molecules as well as their binding strengths to the
MOF host, and sheds light on the specific guest adsorption mechanisms. Variable
temperature (13)C SSNMR spectra of (13)CO2 adsorbed within various forms of MIL
53 are acquired and analyzed. CO2 undergoes a combination of two motions within
MIL-53; we report the types of motion present, their rates, and rotational
angles. (1)H-(13)C CP SSNMR experiments are used to examine the proximity of (1)H
atoms in the MOF to (13)C atoms in CO2 guests. By replacing (1)H with (2)H in MIL
53, the location of the CO2 adsorption site in MIL-53 is experimentally confirmed
by (1)H-(13)C CP SSNMR. The binding strength of CO2 within these MIL-53 MOFs
follows the order MIL-53-NH2 (Al) > MIL-53-NH2 (Ga) > MIL-53 (Al) > MIL-53 (Ga).
PMID- 26427011
TI - Reduced Dentin Matrix Protein Expression in Camurati-Engelmann Disease Transgenic
Mouse Model.
AB - Overexpression of transforming growth factor-beta1 (TGF-beta1) has been shown to
lead to mineralization defects in both the enamel and dentin layers of teeth. A
TGFB1 point mutation (H222D), derived from published cases of Camurati-Engelmann
disease (CED), has been shown to constitutively activate TGF-beta1, leading to
excess bone matrix production. Although CED has been well documented in clinical
case reports, there are no published studies on the effect of CED on the
dentition. The objective of this study was to determine the dental manifestations
of hyperactivated TGF-beta1 signaling using an established mouse model of CED
derived TGF-beta1 mutation. Murine dental tissues were studied via radiography,
micro-CT, immunohistochemistry, and qRT-PCR. Results showed that initial
decreased dental mineralized tissue density is resolved. Proliferation assays of
incisor pulp and alveolar bone cell cultures revealed that cells from transgenic
animals displayed a reduced rate of growth compared to alveolar bone cultures
from wild-type mice. TGF-beta family gene expression analysis indicated
significant fold changes in the expression of Alpl, Bmp2-5, Col-1, -2, -4, and
6, Fgf, Mmp, Runx2, Tgfb3, Tfgbr3, and Vdr genes. Assessment of SIBLINGs revealed
downregulation of Ibsp, Dmp1, Dspp, Mepe, and Spp1, as well as reduced staining
for BMP-2 and VDR in mesenchymal-derived pulp tissue in CED animals. Treatment of
dental pulp cells with recombinant human TGF-beta1 resulted in increased SIBLING
gene expression. CONCLUSIONS: Our results provide in vivo evidence suggesting
that TFG-beta1 mediates expression of important dentin extracellular matrix
components secreted by dental pulp, and when unbalanced, may contribute to
abnormal dentin disorders.
PMID- 26427012
TI - Finite Element Model Analysis of Cephalic Trim on Nasal Tip Stability.
AB - IMPORTANCE: Alar rim retraction is the most common unintended consequence of
tissue remodeling that results from overresection of the cephalic lateral crural
cartilage; however, the complex tissue remodeling process that produces this
shape change is not well understood. OBJECTIVES: To simulate how resection of
cephalic trim alters the stress distribution within the human nose in response to
tip depression (palpation) and to simulate the internal forces generated after
cephalic trim that may lead to alar rim retraction cephalically and upward
rotation of the nasal tip. DESIGN, SETTING, AND PARTICIPANTS: A multicomponent
finite element model was derived from maxillofacial computed tomography with 1-mm
axial resolution. The 3-dimensional editing function in the medical imaging
software was used to trim the cephalic portion of the lower lateral cartilage to
emulate that performed in typical rhinoplasty. Three models were created: a
control, a conservative trim, and an aggressive trim. Each simulated model was
imported to a software program that performs mechanical simulations, and material
properties were assigned. First, nasal tip depression (palpation) was simulated,
and the resulting stress distribution was calculated for each model. Second, long
term tissue migration was simulated on conservative and aggressive trim models by
placing normal and shear force vectors along the caudal and cephalic borders of
the tissue defect. RESULTS: The von Mises stress distribution created by a 5-mm
tip depression revealed consistent findings among all 3 simulations, with regions
of high stress being concentrated to the medial portion of the intermediate crus
and the caudal septum. Nasal tip reaction force marginally decreased as more
lower lateral cartilage tissue was resected. Conservative and aggressive cephalic
trim models produced some degree of alar rim retraction and tip rotation, which
increased with the magnitude of the force applied to the region of the tissue
defect. CONCLUSIONS AND RELEVANCE: Cephalic trim was performed on a computerized
composite model of the human nose to simulate conservative and aggressive trims.
Internal forces were applied to each model to emulate the tissue migration that
results from decades of wound healing. Our simulations reveal that the degree of
tip rotation and alar rim retraction is dependent on the amount of cartilage that
was resected owing to cephalic trim. Tip reaction force is marginally reduced
with increasing tissue volume resection. LEVEL OF EVIDENCE: NA.
PMID- 26427014
TI - Experimental and theoretical photoluminescence studies in nucleic acid assembled
gold-upconverting nanoparticle clusters.
AB - Combinations of rare earth doped upconverting nanoparticles (UCNPs) and gold
nanostructures are sought as nanoscale theranostics due to their ability to
convert near infrared (NIR) photons into visible light and heat, respectively.
However, because the large NIR absorption cross-section of the gold coupled with
their thermo-optical properties can significantly hamper the photoluminescence of
UCNPs, methods to optimize the ratio of gold nanostructures to UCNPs must be
developed and studied. We demonstrate here nucleic acid assembly methods to
conjugate spherical gold nanoparticles (AuNPs) and gold nanostars (AuNSs) to
silica-coated UCNPs and probe the effect on photoluminescence. These studies
showed that while UCNP fluorescence enhancement was observed from the AuNPs
conjugated UCNPs, AuNSs tended to quench fluorescence. However, conjugating lower
ratios of AuNSs to UCNPs led to reduced quenching. Simulation studies both
confirmed the experimental results and demonstrated that the orientation and
distance of the UCNP with respect to the core and arms of the gold nanostructures
played a significant role in PL. In addition, the AuNS-UCNP assemblies were able
to cause rapid gains in temperature of the surrounding medium enabling their
potential use as a photoimaging-photodynamic-photothermal agent.
PMID- 26427013
TI - Ternary Dinuclear Copper(II) Complexes of a Reduced Schiff Base Ligand with
Diimine Coligands: DNA Binding, Cytotoxic Cell Apoptosis, and Apoptotic
Mechanism.
AB - A serial of mixed-ligand Cu(II) complexes of the type [Cu(phens)(H2 PDILeu)]H2 O
(1-4) containing phens as 2,2'-bipyridyl (bpy, 1), 1,10-phenanthroline (phen, 2),
dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3), and dipyrido[3,2-a:2',3'-c]phenazine
(dppz, 4) have been isolated and characterized. The interaction of the complexes
with calf-thymus DNA has been explored by physical methods to propose modes of
DNA binding of the complexes, which indicate that 4 interacts with DNA more
strongly than all of the other complexes through intercalation interaction.
Furthermore, cell apoptosis was detected by AnnexinV/PI flow cytometry and TUNEL
assay and by Western blotting to detect the protein expression of p53, Bax, and
Bcl-2. All the three copper complexes can effectively induce apoptosis of the
three human tumor cells, which was accompanied with upregulation of the
expression of p53 and Bax, while Bcl-2 decreased.
PMID- 26427015
TI - X-ray structure of a Ni(II)-tri-phenoxyl radical complex.
AB - The diimino-diphenolato neutral square-planar Ni(ii) complex, NiL2, is readily
oxidised with 2 equiv. of Ag[SbF6], to produce an unprecedented octahedral Ni(ii)
tris(phenoxyl) radical complex, [Ni(L)3][SbF6]2. This study reveals, for the
first time, the X-ray structure of a metal-tri-phenoxyl radical complex.
PMID- 26427016
TI - Knockdown of LRP/LR Induces Apoptosis in Breast and Oesophageal Cancer Cells.
AB - Cancer is a global burden due to high incidence and mortality rates and is ranked
the second most diagnosed disease amongst non-communicable diseases in South
Africa. A high expression level of the 37kDa/67kDa laminin receptor (LRP/LR) is
one characteristic of cancer cells. This receptor is implicated in the
pathogenesis of cancer cells by supporting tumor angiogenesis, metastasis and
especially for this study, the evasion of apoptosis. In the current study, the
role of LRP/LR on cellular viability of breast MCF-7, MDA-MB 231 and WHCO1
oesophageal cancer cells was investigated. Western blot analysis revealed that
total LRP expression levels of MCF-7, MDA-MB 231 and WHCO1 were significantly
downregulated by targeting LRP mRNA using siRNA-LAMR1. This knockdown of LRP/LR
resulted in a significant decrease of viability in the breast and oesophageal
cancer cells as determined by an MTT assay. Transfection of MDA-MB 231 cells with
esiRNA-RPSA directed against a different region of the LRP mRNA had similar
effects on LRP/LR expression and cell viability compared to siRNA-LAMR1,
excluding an off-target effect of siRNA-LAMR1. This reduction in cellular
viability is as a consequence of apoptosis induction as indicated by the exposure
of the phosphatidylserine protein on the surface of breast MCF-7, MDA-MB 231 and
oesophageal WHCO1 cancer cells, respectively, detected by an Annexin-V/FITC assay
as well as nuclear morphological changes observed post-staining with Hoechst.
These observations indicate that LRP/LR is crucial for the maintenance of
cellular viability of breast and oesophageal cancer cells and recommend siRNA
technology targeting LRP expression as a possible novel alternative technique for
breast and oesophageal cancer treatment.
PMID- 26427017
TI - Prevalence and Incidence of Epilepsy Associated with Convulsive Seizures in Rural
Bolivia. A Global Campaign against Epilepsy Project.
AB - OBJECTIVE: we performed a three-stages door-to-door survey to estimate incidence
and prevalence of epilepsy associated with convulsive seizures (EACS) in a rural
area of Bolivia. METHODS: the study was carried out in the Cordillera Province,
southern-eastern Bolivia. One hundred fourteen rural communities with a total
population of 18,907 inhabitants were included in the survey. In order to
identify subjects with EACS, trained fieldworkers administered a validated single
screening question to the householders (stage I). A second face-to-face
questionnaire was administered to each positive subject (stage II) that, in case
of positive answer, underwent a complete neurological examination to confirm the
diagnosis (stage III). We estimated age and sex specific life-time and active
EACS prevalence at the prevalence day (30th June 2010). Incidence risk was
evaluated for the 10-year period between January 2000 and December 2010. RESULTS:
on prevalence day we identified 136 subjects with EACS, 124 of whom had active
epilepsy. The life-time prevalence of EACS was 7.2/1,000 (7.6/1,000 age-adjusted
to the world standard population) while the prevalence of active EACS was
6.6/1,000 (6.7/1,000 age-adjusted to the world standard population). Both life
time and active prevalence showed a peak (10.3/1,000) in the 15-24 years age
group and, overall, were higher among women. During the incidence study period,
105 patients living in the study area had the onset of EACS. The crude incidence
risk was 55.4/100,000 (49.5/100,000 age-adjusted to the world standard
population). Incidence was slightly but not significantly higher among women
(58.9/100,000 versus 51.9/100,000). CONCLUSIONS: the present study demonstrated a
considerable burden of EACS in the Bolivian Chaco, showing prevalence and
incidence estimates close to those reported for low and middle- income countries
and underlying the need of treatment programs.
PMID- 26427018
TI - Antimony(III) complexes with 2-amino-4,6-dimethoxypyrimidines: Synthesis,
characterization and biological evaluation.
AB - Novel pyrimidine compound bearing disulfide bridge, 5,5'-disulfanediylbis(2-amino
4,6-dimetoxypyrimidine) (3) was synthesized by reduction of 2-amino-4,6-dimethoxy
5-thiocyanatopyrimidine for the first time, and its structure was confirmed by X
ray crystallographic analysis. Novel binuclear antimony(III) compound of (3),
{Sb[5,5'-disulfanediylbis(2-amino-4,6-dimetoxypyrimidine)]Cl3}2 (4) and
mononuclear antimony(III) compounds, SbL2Cl3, [L: 2-amino-5-thiol-4,6-dimethoxy
pyrimidine (2) and 2-amino-5-(1H-tetrazol-5-ylthio)-4,6-dimethoxypyrimidine (6)]
were synthesized and characterized with the help of elemental analysis, molecular
conductivity, FT-IR, (1)H-NMR and LC-MS techniques. The geometrical structures
optimized by a DFT/B3LYP/LANL2DZ method of the compounds, indicated that
monomeric compounds have square pyramidal shape. Both antileishmanial activity
against Leishmania tropica promastigote and glutathione reductase inhibitory
activity were determined in vitro. The results showed that (3) has the best
biological activity.
PMID- 26427020
TI - The relationship between chemical concentration and odor activity value explains
the inconsistency in making a comprehensive surrogate scent training tool
representative of illicit drugs.
AB - This report highlights the importance of an individual chemical's odor impact in
the olfactory identification of marijuana, cocaine, and heroin. There are small
amounts of highly odorous compounds present in headspace of these drugs, with
very low odor detection thresholds, that are more likely responsible for
contributing to the overall odor of these drugs. Previous reports of the most
abundant compounds in headspace can mislead researchers when dealing with whole
odor of these drugs. Surrogate scent formulations, therefore, must match the odor
impact of key compounds and not just the chemical abundance of compounds. The
objective of this study was to compare odorous volatile organic compounds (VOCs)
emitted from illicit drug samples of marijuana, cocaine, and heroin to surrogate
smell formulations using simultaneous sensory (via human olfaction) and chemical
analyses. Use of solid phase microextraction (SPME) allowed VOCs in drug
headspace to be extracted and pre-concentrated on site, and analyzed by
multidimensional gas chromatography-mass spectrometry-olfactometry (MDGC-MS-O).
Use of MDGC-MS-O allowed for further separation of odorous compounds and
simultaneous detection by the human nose of the separate odor parts that make up
the total aroma of these drugs. The compounds most abundant in headspace were not
the most odor impactful when ranked by odor activity values (OAVs) (defined as
ratio of concentration to odor detection threshold, ODT). There were no apparent
correlations between concentrations and OAVs. A 1g marijuana surrogate lacked in
odor active acids, aldehydes, ethers, hydrocarbons, N-containing, and S
containing VOCs and was overabundant in odor active alcohols and aromatics
compared with real marijuana. A 1g cocaine surrogate was overabundant in odor
active alcohols, aldehydes, aromatics, esters, ethers, halogenates, hydrocarbons,
ketones and N-containing compounds compared with real. A 1g heroin surrogate
should contain less odor active acids, alcohols, aromatics, esters, ketones, and
N-containing compounds. Drug quantity, age and adulterants can affect VOC
emissions and their odor impact. The concept of odor activity value, then, is
useful to researchers without access to more sophisticated instrumentation. Odor
activity values can be calculated from published odor detection thresholds. More
research is warranted to expand the database, and determine odor detection
thresholds for compounds of interest. Additional information could be obtained
from establishing ODTs of key odorants for canines.
PMID- 26427019
TI - Oral administration of hyaluronan prevents skin dryness and epidermal thickening
in ultraviolet irradiated hairless mice.
AB - Hyaluronan is a component of the extracellular matrix that plays a role in water
retention in tissues. In this study, we orally administered hyaluronans of
varying molecular weights (300k and less than 10k) repeatedly to hairless mice
exposed to ultraviolet (UV) irradiation and examined their effects on the skin of
these mice. UV irradiation induces a marked increase in the epidermal thickness
of the dorsal skin and a marked decrease in the skin moisture content; however,
orally administered hyaluronan, particularly that with a molecular weight of less
than 10k, markedly reversed the increase and decrease in the epidermal thickness
and skin moisture content, respectively. Furthermore, on analyzing the mice skin,
orally administered hyaluronan with a molecular weight of less than 10k increased
the levels of the HAS2 gene expression in the skin. Based on these findings, it
is assumed that orally administered hyaluronans, with molecular weight of 300k
and less than 10k, reversed UV irradiation-induced skin disturbance. In
particular, it was considered that the increase in the skin moisture content by
orally administered hyaluronan, with a molecular weight of less than 10k, was
related to the effect on skin cells.
PMID- 26427021
TI - Differential grandparental investment - the impact of phenotypic resemblance.
AB - Differential grandparental investment is mainly explained as a result of
paternity uncertainty. Phenotypic resemblance may be interpreted as an indicator
of genetically relatedness. Consequently the present study focused on the impact
of phenotypic resemblance on grandparental investment, i.e. solicitude, contact
frequency and quality of relationship. 213 adults persons between the age 19 and
32 years (x = 25.5; SD = 3.4) were enrolled in the study. Data concerning
grandparental investment during childhood were collected retrospectively using a
30 item questionnaire. Grandparental investment patterns differed significantly
according grandparent category. In detail maternal grandmothers showed the
highest contact frequency and the highest solicitude while - as to be expected -
the paternal grandfather exhibited the lowest degree of investment. Grandparental
investment was independent of grandparent category mainly influenced by
residential distance. Phenotypic resemblance had an impact on grandparental
investment independent of residential distance. This was first of all true of
paternal grandfathers. An impact of phenotypic resemblance on grandparental
investment patters can be assumed.
PMID- 26427022
TI - Self-catalytic polymerization of a water-soluble selenium/polypyrrole
nanocomposite and its nonlinear optical properties.
AB - A facile one-step method for the synthesis of a water-soluble
selenium/polypyrrole (Se/PPy) nanocomposite was developed. In the aqueous
synthesis process, the pyrrole acted as a reductant for the reduction of H2SeO3,
and then the elemental Se formed in situ acted as a catalyst for the
polymerization of pyrrole. The characterization results show that the as-obtained
composite (Se/PPy) is a spherical (Phi80 nm) product that is made up of amorphous
Se particles coated by PPy layers. The formation mechanism and influence factors
of the products were discussed, based on a series of experiments. It is proposed
that remainder H2SeO3 adsorbed on the PPy chains increased the water-solubility
and conductivity of the Se/PPy nanocomposite. Significantly, relying on the
synergistic effect of photo-conductive Se nanoparticles and electric-conductive
PPy molecules, the Se/PPy nanocomposite possesses a large two-photon absorption
(2PA) cross-section and good optical limiting properties, which were demonstrated
by the Z-scan technique using a femtosecond laser. We believe that this work
should be an interesting strategy for developing polymer composites with
excellent optoelectrical properties.
PMID- 26427023
TI - Dynamics of Weeds in the Soil Seed Bank: A Hidden Markov Model to Estimate Life
History Traits from Standing Plant Time Series.
AB - Predicting the population dynamics of annual plants is a challenge due to their
hidden seed banks in the field. However, such predictions are highly valuable for
determining management strategies, specifically in agricultural landscapes. In
agroecosystems, most weed seeds survive during unfavourable seasons and persist
for several years in the seed bank. This causes difficulties in making accurate
predictions of weed population dynamics and life history traits (LHT).
Consequently, it is very difficult to identify management strategies that limit
both weed populations and species diversity. In this article, we present a method
of assessing weed population dynamics from both standing plant time series data
and an unknown seed bank. We use a Hidden Markov Model (HMM) to obtain estimates
of over 3,080 botanical records for three major LHT: seed survival in the soil,
plant establishment (including post-emergence mortality), and seed production of
18 common weed species. Maximum likelihood and Bayesian approaches were
complementarily used to estimate LHT values. The results showed that the LHT
provided by the HMM enabled fairly accurate estimates of weed populations in
different crops. There was a positive correlation between estimated germination
rates and an index of the specialisation to the crop type (IndVal). The
relationships between estimated LHTs and that between the estimated LHTs and the
ecological characteristics of weeds provided insights into weed strategies. For
example, a common strategy to cope with agricultural practices in several weeds
was to produce less seeds and increase germination rates. This knowledge,
especially of LHT for each type of crop, should provide valuable information for
developing sustainable weed management strategies.
PMID- 26427024
TI - Prevalence of malaria across Papua New Guinea after initial roll-out of
insecticide-treated mosquito nets.
AB - OBJECTIVES: To assess the population prevalence of malaria in villages across
Papua New Guinea (PNG) following the first roll-out of free long-lasting
insecticidal nets (LLIN). METHODS: Between October 2008 and August 2009, a
household survey was conducted in 49 random villages in districts covered by the
LLIN distribution campaign. The survey extended to 19 villages in sentinel sites
that had not yet been covered by the campaign. In each village, 30 households
were randomly sampled, household heads were interviewed and capillary blood
samples were collected from all consenting household members for microscopic
diagnosis of malaria. RESULTS: Malaria prevalence ranged from 0% to 49.7% with a
weighted average of 12.1% (95% CI 9.5, 15.3) in the national sample. More people
were infected with Plasmodium falciparum (7.0%; 95% CI 5.4, 9.1) than with P.
vivax (3.8%; 95% CI 2.4, 5.7) or P. malariae (0.3%; 95% CI 0.1, 0.6).
Parasitaemia was strongly age-dependent with a P. falciparum peak at age 5-9
years and a P. vivax peak at age 1-4 years, yet with differences between
geographical regions. Individual LLIN use and high community coverage were
associated with reduced odds of infection (OR = 0.64 and 0.07, respectively; both
P < 0.001). Splenomegaly in children and anaemia were common morbidities
attributable to malaria. CONCLUSIONS: Malaria prevalence across PNG is again at
levels comparable to the 1970s. The strong association of LLIN use with reduced
parasitaemia supports efforts to achieve and maintain high country-wide coverage.
P. vivax infections will require special targeted approaches across PNG.
PMID- 26427025
TI - Nanoparticles made of pi-conjugated compounds targeted for chemical and
biological applications.
AB - Semiconducting organic nanoparticles have recently attracted increasing attention
in the chemical and biomedical fields. Such nanoparticles are mainly composed of
pi-conjugated compounds. They possess the properties of easy synthesis, facile
tuning, less toxicity and more biocompatibility relative to the existing
inorganic nanoparticles. In addition, they show advantages such as brighter
fluorescence, higher photostability and higher biocompatibility, compared with
classical fluorescent organic dyes. In this review, we summarize the latest
advances in the development of organic nanoparticles made of pi-conjugated
compounds, including preparation methods, material design, nanoparticle
fabrication and surface functionalization for chemical and biological
applications. Especially, we focus on the applications of semiconducting organic
nanoparticles in chemical and biological sensing by monitoring the fluorescence
signal, as nanocarriers for drug/gene delivery, in photothermal and photodynamic
therapy, and in photoacoustic imaging. Finally, the challenges and perspectives
for the future development of organic nanoparticles based on pi-conjugated
compounds are also discussed.
PMID- 26427026
TI - The Synthesis of B2(SIDip)2 and its Reactivity Between the Diboracumulenic and
Diborynic Extremes.
AB - A new compound with the formula L-B2-L wherein the stabilizing ligand (L) is 1,3
bis[diisopropylphenyl]-4,5-dihydroimidazol-2-ylidene (SIDip) has been
synthesized, isolated, and characterized. The pi-acidity of the SIDip ligand,
intermediate between the relatively non-acidic IDip (1,3
bis[diisopropylphenyl]imidazol-2-ylidene) ligand and the much more highly acidic
CAAC (1-[2,6-diisopropylphenyl]-3,3,5,5-tetramethylpyrrolidin-2-ylidene) ligand,
gives rise to a compound with spectroscopic, electrochemical, and structural
properties between those of L-B2-L compounds stabilized by CAAC and IDip.
Reactions of all three L-B2-L compounds with CO demonstrate the differences
caused by their respective ligands, as the pi-acidities of the CAAC and SIDip
carbenes enabled the isolation of bis(boraketene) compounds (L(OC)B-B(CO)L),
which could not be isolated from reactions with B2(IDip)2. However, only
B2(IDip)2 and B2(SIDip)2 could be converted into bicyclic bis(boralactone)
compounds.
PMID- 26427028
TI - What is your diagnosis? A soft tissue mass in a Black Rat Snake.
PMID- 26427029
TI - Rapid changes in genetic architecture of behavioural syndromes following
colonization of a novel environment.
AB - Behavioural syndromes, that is correlated behaviours, may be a result from
adaptive correlational selection, but in a new environmental setting, the trait
correlation might act as an evolutionary constraint. However, knowledge about the
quantitative genetic basis of behavioural syndromes, and the stability and
evolvability of genetic correlations under different ecological conditions, is
limited. We investigated the quantitative genetic basis of correlated behaviours
in the freshwater isopod Asellus aquaticus. In some Swedish lakes, A. aquaticus
has recently colonized a novel habitat and diverged into two ecotypes, presumably
due to habitat-specific selection from predation. Using a common garden approach
and animal model analyses, we estimated quantitative genetic parameters for
behavioural traits and compared the genetic architecture between the ecotypes. We
report that the genetic covariance structure of the behavioural traits has been
altered in the novel ecotype, demonstrating divergence in behavioural
correlations. Thus, our study confirms that genetic correlations behind
behaviours can change rapidly in response to novel selective environments.
PMID- 26427027
TI - Functional Impact and Evolution of a Novel Human Polymorphic Inversion That
Disrupts a Gene and Creates a Fusion Transcript.
AB - Despite many years of study into inversions, very little is known about their
functional consequences, especially in humans. A common hypothesis is that the
selective value of inversions stems in part from their effects on nearby genes,
although evidence of this in natural populations is almost nonexistent. Here we
present a global analysis of a new 415-kb polymorphic inversion that is among the
longest ones found in humans and is the first with clear position effects. This
inversion is located in chromosome 19 and has been generated by non-homologous
end joining between blocks of transposable elements with low identity. PCR
genotyping in 541 individuals from eight different human populations allowed the
detection of tag SNPs and inversion genotyping in multiple populations worldwide,
showing that the inverted allele is mainly found in East Asia with an average
frequency of 4.7%. Interestingly, one of the breakpoints disrupts the
transcription factor gene ZNF257, causing a significant reduction in the total
expression level of this gene in lymphoblastoid cell lines. RNA-Seq analysis of
the effects of this expression change in standard homozygotes and inversion
heterozygotes revealed distinct expression patterns that were validated by
quantitative RT-PCR. Moreover, we have found a new fusion transcript that is
generated exclusively from inverted chromosomes around one of the breakpoints.
Finally, by the analysis of the associated nucleotide variation, we have
estimated that the inversion was generated ~40,000-50,000 years ago and, while a
neutral evolution cannot be ruled out, its current frequencies are more
consistent with those expected for a deleterious variant, although no significant
association with phenotypic traits has been found so far.
PMID- 26427030
TI - Estimating glomerular filtration rate by serum creatinine or/and cystatin C
equations: An analysis of multi-centre Chinese subjects.
AB - AIM: Various equations based on serum creatinine or/and cystatin C, required
further validation in a Chinese population. We compared the performance of six
Chinese equations (Mascr, Peiscr, Macys, Fengcys, Mascr-cys and Fengscr-cys) with
the CKD-EPI equations in multi-centre Chinese subjects and evaluated their
applicability in clinical practice. METHODS: A total of 1522 adult patients from
four different hospitals of China were enrolled in the study. (99m) Tc-DTPA renal
dynamic imaging was used as the reference GFR (rGFR), and serum creatinine and
cystatin C were measured by standardized assays. An optimal score system was
implemented in the study. RESULTS: The average rGFR of recruited subjects was
67.30+/-28.89 mL/min per 1.73m(2) . All estimated GFR (eGFR) correlated well with
rGFR. In accordance with Bland-Altman analysis, the Fengscr-cys equations
achieved optimal overall performance (score 14 vs 0-6), with least bias (median
difference, -0.57 mL/min per 1.73m(2) ; median absolute difference, 8.83 mL/min
per 1.73m(2) ), best precision (17.99 mL/min per 1.73m(2) ), highest accuracy
(percentage of eGFR within 15%, 30% and 50% of the rGFR (P15 , P30 and P50 ;
49.7%, 78.7% and 91.8%, respectively); root-mean-square-error (RMSE, 16.28)). The
Fengcys equation, a typical cystatin C based equation, was another well-behaved
formula with an impressive performance. The Ma equations performed much poorer
than the CKD-EPI equations. Consistent results can be observed in the GFR- /age-
and sex-specific subgroups, while none equation yielded ideal accuracy in GFR<60
mL/min per 1.73 m(2) subgroup. CONCLUSION: The Fengscr-cys equation appeared to
achieve the best performance for GFR estimation in overall Chinese adult
patients. However, further research is warranted to improve the accuracy of
available equations in GFR less than 60 mL/min per 1.73 m(2) individuals.
PMID- 26427031
TI - Congruent phylogenetic and fossil signatures of mammalian diversification
dynamics driven by Tertiary abiotic change.
AB - Computational methods for estimating diversification rates from extant species
phylogenetic trees have become abundant in evolutionary research. However, little
evidence exists about how their outcome compares to a complementary and direct
source of information: the fossil record. Furthermore, there is virtually no
direct test for the congruence of evolutionary rates based on these two sources.
This task is only achievable in clades with both a well-known fossil record and a
complete phylogenetic tree. Here, we compare the evolutionary rates of ruminant
mammals as estimated from their vast paleontological record--over 1200 species
spanning 50 myr--and their living-species phylogeny. Significantly, our results
revealed that the ruminant's fossil record and phylogeny reflect congruent
evolutionary processes. The concordance is especially strong for the last 25 myr,
when living groups became a dominant part of ruminant diversity. We found
empirical support for previous hypotheses based on simulations and neontological
data: The pattern captured by the tree depends on how clade specific the
processes are and which clades are involved. Also, we report fossil evidence for
a postradiation speciation slowdown coupled with constant, moderate extinction in
the Miocene. The recent deceleration in phylogenetic rates is connected to rapid
extinction triggered by recent climatic fluctuations.
PMID- 26427032
TI - Dendritic cells revisited in human allergic rhinitis and asthma.
AB - The role of dendritic cells (DCs) in airway allergy has been studied for 15
years; recent data has highlighted the cross talk with airway epithelial cells
and environmental factors (allergens, virus) during the inception and
exacerbation of allergic asthma. Although murine models have provided key
information, it remains uncertain to what extent these basic mechanisms take
place in human allergic disease, notably with regard to different clinical
phenotypes. In the present review, we discuss new evidence regarding mechanisms
of DC regulation in the mouse which could be important in human asthma. Finally,
after discussing the effects of current therapies on DC biology, we focus on
pathways that could represent targets for future therapies.
PMID- 26427034
TI - Efficacy of disinfectants against porcine rotavirus in the presence and absence
of organic matter.
AB - Rotavirus is an enteric pathogen that causes morbidity and mortality in young
mammals, including pigs. Outbreaks of rotavirus on commercial farms have a
significant economic impact in terms of losses in production. Effective cleaning
and disinfection along with good farm management can reduce rotavirus
contamination in the environment, and decrease the chance of outbreaks of
disease. This study investigated the efficacy of six commercial disinfectants
against MS2 bacteriophage and Group A porcine rotavirus, in the presence of high
and low levels of organic matter to simulate the farm environment. A phenolic
based disinfectant (Bi-OO-cyst) was effective at all levels of organic matter
concentrations. Iodophore-based disinfectants did not have a significant
virucidal effect against rotavirus under any conditions. For peroxygen compound
based disinfectants and glutaraldehyde-based disinfectants, organic matter load
made a significant difference in reducing efficacy. This highlights the
importance of thorough cleaning with detergent before disinfection to reduce
viral contamination on the farm and decrease rotavirus disease incidence in pigs.
SIGNIFICANCE AND IMPACT OF THE STUDY: Infection of rotavirus has a negative
impact on the health and growth of pigs in production. Given that the virus is
transmitted faecal-orally, use of an effective disinfectant on farm, which works
even in high organic matter, has the potential to save costs in terms of
outbreaks of disease and viral contamination. Here, we test a number of
commercial disinfectants of which one a phenolic compound, Bio-OO-cyst, shows
effectivity even in high organic matter, implying its use could have a huge
impact in reducing viral contamination and preventing losses in production.
PMID- 26427033
TI - Sodium stibogluconate and paromomycin for treating visceral leishmaniasis under
routine conditions in eastern Sudan.
AB - OBJECTIVES: Among patients with primary and relapse visceral leishmaniasis (VL)
in eastern Sudan, we determined the proportion eligible for treatment with sodium
stibogluconate and paromomycin (SSG/PM) and, of these, their demographic and
clinical characteristics; initial treatment outcomes including adverse side
effects requiring treatment discontinuation; treatment outcomes by 6 months; and
risk factors associated with initial (slow responders) and late treatment failure
(relapses and post-kala-azar dermal leishmaniasis, PKDL). METHODS: A
retrospective cohort study in Tabarak Allah Hospital, Gedaref Province, eastern
Sudan, from July 2011 to January 2014. RESULTS: Of 1252 individuals diagnosed
with VL (1151 primary and 101 relapses), 65% were eligible for SSG/PM including
83% children, almost half of them malnourished and anaemic. About 4% of
individuals discontinued treatment due to side effects; 0.7% died during
treatment. Initial cure was achieved in 93% of 774 primary cases and 77% of 35
relapse cases (P < 0.001). Among the 809 patients eligible for SSG/PM, 218 (27%)
were lost to follow-up. Outcomes by six months among the 591 patients with
available follow-up data were: definitive cure (n = 506; 86%), relapse (n = 38;
6%), treatment discontinuation (n = 33; 6%), PKDL (n = 7; 1%) and death (n = 7;
1%). Among those completing a full course of SSG/PM, relapses and under-fives
were at significantly higher risk of early and late treatment failure,
respectively. CONCLUSION: Whether SSG/PM as a first-line regimen is an undeniable
progress compared to SSG monotherapy, it excluded a considerable proportion of VL
patients due to drug safety concerns. We call for accelerated development of new
drugs and treatment regimens to improve VL treatment in Sudan.
PMID- 26427035
TI - Improving healthcare worker hand hygiene adherence before patient contact: A
multimodal intervention of hand hygiene practice in Three Japanese tertiary care
centers.
AB - BACKGROUND: Though hand hygiene is an important method of preventing healthcare
associated infection, we found suboptimal hand hygiene adherence among healthcare
workers in 4 diverse Japanese hospitals (adherence rates of 11%-25%). OBJECTIVE:
Our goal was to assess multimodal hand hygiene intervention coupled with a
contest to improve hand hygiene adherence. SETTING: A total of 3 to 4 inpatient
wards in 3 Japanese hospitals. DESIGN: Pre-post intervention study. INTERVENTION:
The intervention was a multimodal hand hygiene intervention recommended by the
World Health Organization that was tailored to each facility. The hospital with
the highest adherence after the intervention was given $5000 US dollars and a
trophy, provided by an American coinvestigator unaffiliated with any of the
Japanese hospitals. MEASUREMENT: We tracked hand hygiene adherence rates before
patient contact for each unit and hospital and compared these to pre-intervention
adherence rates. RESULTS: We observed 2982 postintervention provider-patient
encounters in 10 units across 3 hospitals. Hand hygiene adherence rates were
improved overall after the intervention (18% pre- to 33% postintervention; P <
0.001), but postintervention adherence rates varied considerably: hospital A +
29%, B + 5%, C + 8%. Hospital A won the contest with 40% adherence after the
intervention. CONCLUSIONS: Using a novel contest coupled with a multimodal
intervention successfully improved hand hygiene rates among Japanese healthcare
workers. Given the overall low rates, however, further improvement is necessary.
PMID- 26427036
TI - The effect of a streptococci containing probiotic in periodontal therapy: a
randomized controlled trial.
AB - AIM: To evaluate the adjunctive effects of a Streptococcus oralis KJ3,
Streptococcus uberis KJ2 and Streptococcus rattus JH145 containing probiotic
tablet after scaling and root planing (SRP). MATERIALS AND METHODS: Forty-eight
periodontitis patients were included in this double-blind, placebo-controlled
clinical trial. After root planing, patients used either a placebo or a probiotic
tablet twice a day for 12 weeks. The pocket probing depth (primary outcome
measure), bleeding on probing and relative attachment levels were measured at
baseline, 12 and 24 weeks. At baseline, 4, 8, 12 and 24 weeks, microbiological
sampling was performed and plaque and gingival indices were recorded. RESULTS:
The primary and secondary outcome measures were significantly (p < 0.05) improved
at the 12- and the 24-week evaluation in both groups. However, no significant
inter-group differences could be detected at any time point, except from the % of
sites with plaque that were significantly lower in the probiotic group than in
the control group at the 24-week evaluation. In addition, at the 12-week time
point, the salivary Prevotella intermedia counts were significantly lower in the
probiotic group. CONCLUSIONS: No differences were detected when comparing the
adjunctive use of a placebo or the investigated streptococci containing probiotic
tablet after SRP. ClinicalTrials.gov Identifier: NCT02403960.
PMID- 26427037
TI - The flavors of plasma cells.
PMID- 26427038
TI - Adenosine: a selfish-immunity signal?
PMID- 26427039
TI - Sub-apoptotic dosages of pro-oxidant vitamin cocktails sensitize human melanoma
cells to NK cell lysis.
AB - Alpha-tocopheryl succinate (alphaTOS), vitamin K3 (VK3) and vitamin C (ascorbic
acid, AA) were previously shown to synergistically promote different death
pathways in carcinoma cells, depending on their concentrations and combinations.
Similar effects were observed herein in melanoma cells, although alphaTOS behaved
as an antagonist. Interestingly, suboptimal cell death-inducing concentrations
(1.5 MUM alphaTOS/20 MUM AA/0.2 MUM VK3) effectively up-regulated activating
Natural Killer (NK) cell ligands, including MICA (the stress-signaling ligand of
the NKG2D receptor), and/or the ligands of at least one of the natural
cytotoxicity receptors (NKp30, NKp44 and NKp46) in 5/6 melanoma cell lines. Only
an isolated MICA down-regulation was seen. HLA class I, HLA class II, ULBP1,
ULBP2, ULBP3, Nectin-2, and PVR displayed little, if any, change in expression.
Ligand up-regulation resulted in improved lysis by polyclonal NK cells armed with
the corresponding activating receptors. These results provide the first evidence
for concerted induction of cell death by cell-autonomous and extrinsic (immune)
mechanisms. Alarming the immune system much below the cell damage threshold may
have evolved as a sensitive readout of neoplastic transformation and oxidative
stress. Cocktails of vitamin analogues at slightly supra-physiological dosages
may find application as mild complements of melanoma treatment, and in
chemoprevention.
PMID- 26427040
TI - Decoding c-Myc networks of cell cycle and apoptosis regulated genes in a
transgenic mouse model of papillary lung adenocarcinomas.
AB - The c-Myc gene codes for a basic-helix-loop-helix-leucine zipper transcription
factor protein and is reported to be frequently over-expressed in human cancers.
Given that c-Myc plays an essential role in neoplastic transformation we wished
to define its activity in lung cancer and therefore studied its targeted
expression to respiratory epithelium in a transgenic mouse disease model. Using
histological well-defined tumors, transcriptome analysis identified novel c-Myc
responsive cell cycle and apoptosis genes that were validated as direct c-Myc
targets using EMSA, Western blotting, gene reporter and ChIP assays.Through
computational analyses c-Myc cooperating transcription factors emerged for
repressed and up-regulated genes in cancer samples, namely Klf7, Gata3, Sox18,
p53 and Elf5 and Cebpalpha, respectively. Conversely, at promoters of genes
regulated in transgenic but non-carcinomatous lung tissue enriched binding sites
for c-Myc, Hbp1, Hif1 were observed. Bioinformatic analysis of tumor
transcriptomic data revealed regulatory gene networks and highlighted mortalin
and moesin as master regulators while gene reporter and ChIP assays in the H1299
lung cancer cell line as well as cross-examination of published ChIP-sequence
data of 7 human and 2 mouse cell lines provided strong evidence for the
identified genes to be c-Myc targets. The clinical significance of findings was
established by evaluating expression of orthologous proteins in human lung
cancer. Taken collectively, a molecular circuit for c-Myc-dependent cellular
transformation was identified and the network analysis broadened the perspective
for molecularly targeted therapies.
PMID- 26427041
TI - Comprehensive portrait of recurrent glioblastoma multiforme in molecular and
clinical characteristics.
AB - Glioblastoma multiforme is the most common primary malignant brain tumor in
adults. In addition to poor response to treatment, a high recurrence rate
contributes to the poor prognosis. The purpose of this study was to investigate
the genetical and clinical characteristics of recurrent glioblastoma. We used
whole transcriptome sequencing data to examine the distribution of molecular
subtypes and gene signatures in 22 recurrent glioblastoma taken from the Chinese
population, and further analyzed biological progression of the tumors, when
compared with primary glioblastoma. The proportion of the classical subtype in
recurrent ones (22%) was lower than that in primary glioblastoma (36%). The
frequency of IDH1 mutations in recurrent glioblastomas was nearly twice that in
primary glioblastomas. TP53 mutations were fewer in proneural recurrent
glioblastomas (20%) but frequent in classical recurrent glioblastomas (80%). The
most common sites of recurrent glioblastomas were the temporal lobe (41%). In
patients diagnosed with recurrent glioblastoma multiforme, 64% were younger than
50 years. Gene set enrichment analysis revealed that chromatin fracture, repair,
and remodeling genes were enriched in recurrent glioblastoma. Our results
highlight the differences in clinical features, molecular subtypes and gene
alterations between primary and recurrent glioblastoma and may be helpful for
targeted therapy for recurrent glioblastoma.
PMID- 26427043
TI - DOT1L: a new therapeutic target for aggressive breast cancer.
PMID- 26427042
TI - Targeted therapy for Epstein-Barr virus-associated gastric carcinoma using low
dose gemcitabine-induced lytic activation.
AB - The constant presence of the viral genome in Epstein-Barr virus (EBV)-associated
gastric cancers (EBVaGCs) suggests the applicability of novel EBV-targeted
therapies. The antiviral nucleoside drug, ganciclovir (GCV), is effective only in
the context of the viral lytic cycle in the presence of EBV-encoded thymidine
kinase (TK)/protein kinase (PK) expression. In this study, screening of the Johns
Hopkins Drug Library identified gemcitabine as a candidate for combination
treatment with GCV. Pharmacological induction of EBV-TK or PK in EBVaGC
originated tumor cells were used to study combination treatment with GCV in vitro
and in vivo. Gemcitabine was found to be a lytic inducer via activation of the
ataxia telangiectasia-mutated (ATM)/p53 genotoxic stress pathway in EBVaGC. Using
an EBVaGC mouse model and a [125I] fialuridine (FIAU)-based lytic activation
imaging system, we evaluated gemcitabine-induced lytic activation in an in vivo
system and confirmed the efficacy of gemcitabine-GCV combination treatment. This
viral enzyme-targeted anti-tumor strategy may provide a new therapeutic approach
for EBVaGCs.
PMID- 26427044
TI - EFTUD2 on innate immunity.
PMID- 26427045
TI - The Complete Mitochondrial Genome of Delia antiqua and Its Implications in
Dipteran Phylogenetics.
AB - Delia antiqua is a major underground agricultural pest widely distributed in
Asia, Europe and North America. In this study, we sequenced and annotated the
complete mitochondrial genome of this species, which is the first report of
complete mitochondrial genome in the family Anthomyiidae. This genome is a double
stranded circular molecule with a length of 16,141 bp and an A+T content of
78.5%. It contains 37 genes (13 protein-coding genes, 22 tRNAs and 2 rRNAs) and a
non-coding A+T rich region or control region. The mitochondrial genome of Delia
antiqua presents a clear bias in nucleotide composition with a positive AT-skew
and a negative GC-skew. All of the 13 protein-coding genes use ATN as an
initiation codon except for the COI gene that starts with ATCA. Most protein
coding genes have complete termination codons but COII and ND5 that have the
incomplete termination codon T. This bias is reflected in both codon usage and
amino acid composition. The protein-coding genes in the D. antiqua mitochondrial
genome prefer to use the codon UUA (Leu). All of the tRNAs have the typical
clover-leaf structure, except for tRNASer(AGN) that does not contain the
dihydrouridine (DHU) arm like in many other insects. There are 7 mismatches with
U-U in the tRNAs. The location and structure of the two rRNAs are conservative
and stable when compared with other insects. The control region between 12S rRNA
and tRNAIle has the highest A+T content of 93.7% in the D. antiqua mitochondrial
genome. The control region includes three kinds of special regions, two highly
conserved poly-T stretches, a (TA)n stretch and several G(A)nT structures
considered important elements related to replication and transcription. The
nucleotide sequences of 13 protein-coding genes are used to construct the
phylogenetics of 26 representative Dipteran species. Both maximum likelihood and
Bayesian inference analyses suggest a closer relationship of D. antiqua in
Anthomyiidae with Calliphoridae, Calliphoridae is a paraphyly, and both
Oestroidea and Muscoidea are polyphyletic.
PMID- 26427046
TI - Interactive Effects of Temperature and UV Radiation on Photosynthesis of
Chlorella Strains from Polar, Temperate and Tropical Environments: Differential
Impacts on Damage and Repair.
AB - Global warming and ozone depletion, and the resulting increase of ultraviolet
radiation (UVR), have far-reaching impacts on biota, especially affecting the
algae that form the basis of the food webs in aquatic ecosystems. The aim of the
present study was to investigate the interactive effects of temperature and UVR
by comparing the photosynthetic responses of similar taxa of Chlorella from
Antarctic (Chlorella UMACC 237), temperate (Chlorella vulgaris UMACC 248) and
tropical (Chlorella vulgaris UMACC 001) environments. The cultures were exposed
to three different treatments: photosynthetically active radiation (PAR; 400-700
nm), PAR plus ultraviolet-A (320-400 nm) radiation (PAR + UV-A) and PAR plus UV-A
and ultraviolet-B (280-320 nm) radiation (PAR + UV-A + UV-B) for one hour in
incubators set at different temperatures. The Antarctic Chlorella was exposed to
4, 14 and 20 degrees C. The temperate Chlorella was exposed to 11, 18 and 25
degrees C while the tropical Chlorella was exposed to 24, 28 and 30 degrees C. A
pulse-amplitude modulated (PAM) fluorometer was used to assess the photosynthetic
response of microalgae. Parameters such as the photoadaptive index (Ek) and light
harvesting efficiency (alpha) were determined from rapid light curves. The damage
(k) and repair (r) rates were calculated from the decrease in PhiPSIIeff over
time during exposure response curves where cells were exposed to the various
combinations of PAR and UVR, and fitting the data to the Kok model. The results
showed that UV-A caused much lower inhibition than UV-B in photosynthesis in all
Chlorella isolates. The three isolates of Chlorella from different regions showed
different trends in their photosynthesis responses under the combined effects of
UVR (PAR + UV-A + UV-B) and temperature. In accordance with the noted strain
specific characteristics, we can conclude that the repair (r) mechanisms at
higher temperatures were not sufficient to overcome damage caused by UVR in the
Antarctic Chlorella strain, suggesting negative effects of global climate change
on microalgae inhabiting (circum-) polar regions. For temperate and tropical
strains of Chlorella, damage from UVR was independent of temperature but the
repair constant increased with increasing temperature, implying an improved
ability of these strains to recover from UVR stress under global warming.
PMID- 26427047
TI - Reliability of measures of quadriceps muscle function using magnetic stimulation.
AB - INTRODUCTION: Magnetic stimulation can be used to assess muscle function by
calculating voluntary activation using an interpolated twitch during maximal
voluntary contractions (MVCs) and control twitches to potentiated muscle. In this
study we assessed the reliability of torque, electromyography (EMG), and
voluntary activation variables. METHODS: Fifteen men completed 5 testing sessions
(2 familiarization and 3 reliability trials) to assess quadriceps femoris muscle
function. Intra- and interday reliability levels of torque and EMG variables were
estimated using typical error +/- 90% confidence limits, expressed as percentage
[coefficient of variation (CV)] and intraclass correlation coefficient. The
smallest worthwhile change was calculated as 0.2 * between-participant standard
deviation. RESULTS: Intra- and interday torque variables for MVC were reliable
(CV < 4%, ICC 0.98, and CV < 5%, ICC 0.99, respectively). EMG variables were less
reliable than torque variables, with CVs ranging from 7% to 18%. CONCLUSION:
Magnetic stimulation of the femoral nerve is a reliable method for assessing
muscle function.
PMID- 26427048
TI - Role of the nucleolus in neurodegenerative diseases with particular reference to
the retina: a review.
AB - The nucleolus has emerged as a key regulator of cellular growth and the response
to stress, in addition to its traditionally understood function in ribosome
biogenesis. The association between nucleolar function and neurodegenerative
disease is increasingly being explored. There is also recent evidence indicating
that the nucleolus may well be crucial in the development of the eye. In this
present review, the role of the nucleolus in retinal development as well as in
neurodegeneration with an emphasis on the retina is discussed.
PMID- 26427049
TI - Acute generalized exanthematous pustulosis induced by Mycoplasma pneumoniae
infection.
PMID- 26427050
TI - Fluorescence-Guided Surgery of Liver Metastasis in Orthotopic Nude-Mouse Models.
AB - We report here the development of fluorescence-guided surgery of liver
metastasis. HT29 human colon cancer cells expressing green fluorescent protein
(GFP) were initially injected in the spleen of nude mice. Three weeks later,
established liver metastases were harvested and implanted on the left lobe of the
liver in other nude mice in order to make an orthotopic liver metastasis model.
Fourteen mice with a single liver metastasis were randomized into bright-light
surgery (BLS) or fluorescence-guided surgery (FGS) groups. Seven mice were
treated with BLS, seven were treated with FGS. Three weeks after implantation,
the left lobe of the liver with a single metastasis was exposed through a median
abdominal incision. BLS was performed under white light. FGS was performed using
a hand-held portable fluorescence imaging system (Dino-Lite). Post-surgical
residual tumor fluorescence was visualized with the OV100 Small Animal Imaging
System. Residual tumor fluorescence after BLS was clearly visualized at high
magnification with the OV100. In contrast, residual tumor fluorescence after FGS
was not detected even at high magnification with the OV100. These results
demonstrate the feasibility of FGS for liver metastasis.
PMID- 26427051
TI - A Non-Interventional Naturalistic Study of the Prescription Patterns of
Antipsychotics in Patients with Schizophrenia from the Spanish Province of
Tarragona.
AB - BACKGROUND: The analysis of prescribing patterns in entire catchment areas
contributes to global mapping of the use of antipsychotics and may improve
treatment outcomes. OBJECTIVE: To determine the pattern of long-term
antipsychotic prescription in outpatients with schizophrenia in the province of
Tarragona (Catalonia-Spain). METHODS: A naturalistic, observational,
retrospective, non-interventional study based on the analysis of registries of
computerized medical records from an anonymized database of 1,765 patients with
schizophrenia treated between 2011 and 2013. RESULTS: The most used antipsychotic
was risperidone, identified in 463 (26.3%) patients, followed by olanzapine in
249 (14.1%), paliperidone in 225 (12.7%), zuclopenthixol in 201 (11.4%),
quetiapine in 141 (8%), aripiprazole in 100 (5.7%), and clozapine in 100 (5.7%).
Almost 8 out of 10 patients (79.3%) were treated with atypical or second
generation antipsychotics. Long-acting injectable (LAI) formulations were used in
44.8% of patients. Antipsychotics were generally prescribed in their recommended
doses, with clozapine, ziprasidone, LAI paliperidone, and LAI risperidone being
prescribed at the higher end of their therapeutic ranges. Almost 7 out of 10
patients (69.6%) were on antipsychotic polypharmacy, and 81.4% were on
psychiatric medications aside from antipsychotics. Being prescribed quetiapine
(OR 14.24, 95% CI 4.94-40.97), LAI (OR 9.99, 95% CI 6.45-15.45), psychiatric co
medications (OR 4.25, 95% CI 2.72-6.64), and paliperidone (OR 3.13, 95% CI 1.23
7.92) were all associated with an increased likelihood of polypharmacy. Being
prescribed risperidone (OR 0.54, 95% CI 0.35-0.83) and older age (OR 0.98, 95% CI
0.97-0.99) were related to a low polypharmacy probability. CONCLUSIONS:
Polypharmacy is the most common pattern of antipsychotic use in this region of
Spain. Use of atypical antipsychotics is extensive. Most patients receive
psychiatric co-medications such as anxiolytics or antidepressants. Polypharmacy
is associated with the use of quetiapine or paliperidone, use of a LAI, younger
age, and psychiatric co-medication.
PMID- 26427052
TI - Heterogeneous Mechanisms of Secondary Resistance and Clonal Selection in Sarcoma
during Treatment with Nutlin.
AB - Nutlin inhibits TP53-MDM2 interaction and is under investigation in soft-tissue
sarcomas (STS) and other malignancies. Molecular mechanisms of secondary
resistance to nutlin in STS are unknown. We performed whole-transcriptome
sequencing (RNA-seq) on three pretreatment and secondary resistant STS cell lines
selected based on their high primary sensitivity to nutlin. Our data identified a
subset of cancer gene mutations and ploidy variations that were positively
selected following treatment, including TP53 mutations in 2 out of 3 resistant
cell lines. Further, secondary resistance to nutlin was associated with
deregulation of apoptosis-related genes and marked productive autophagy, the
inhibition of which resulted in significant restoration of nutlin-induced cell
death. Collectively, our findings argue that secondary resistance to nutlin in
STS involved heterogeneous mechanisms resulting from clonal evolution and several
biological pathways. Alternative dosing regimens and combination with other
targeted agents are needed to achieve successful development of nutlin in the
clinical setting.
PMID- 26427053
TI - Attenuation of Inflammatory Mediators (TNF-alpha and Nitric Oxide) and Up
Regulation of IL-10 by Wild and Domesticated Basidiocarps of Amauroderma rugosum
(Blume & T. Nees) Torrend in LPS-Stimulated RAW264.7 Cells.
AB - Amauroderma rugosum, commonly known as "Jiazi" in China, is a wild mushroom
traditionally used by the Chinese to reduce inflammation, to treat diuretic and
upset stomach, and to prevent cancer. It is also used by the indigenous
communities in Malaysia to prevent epileptic episodes and incessant crying by
babies. The aim of this study was to compare the wild and domesticated
basidiocarps of A. rugosum for antioxidant and in vitro anti-inflammatory effects
in LPS-stimulated RAW264.7 cells. The wild basidiocarps of A. rugosum were
collected from the Belum Forest, Perak, Malaysia and the domesticated
basidiocarps of A. rugosum were cultivated in the mushroom house located in the
University of Malaya, Kuala Lumpur, Malaysia. Both the wild and domesticated
basidiocarps were subjected to ethanolic extraction and the extracts were tested
for antioxidant and anti-inflammatory activities. In this study, the crude
ethanolic extract of wild (WB) and domesticated (DB) basidiocarps of A. rugosum
had comparable total phenolic content and DPPH scavenging activity. However, WB
(EC50 = 222.90 MUg/mL) displayed a better ABTS cation radical scavenging activity
than DB (EC50 = 469.60 MUg/mL). Both WB and DB were able to scavenge nitric oxide
(NO) radical and suppress the NO production in LPS-stimulated RAW264.7 cells and
this effect was mediated through the down-regulation of inducible nitric oxide
synthase (iNOS) gene. In addition, both WB and DB caused down-regulation of the
inflammatory gene TNF-alpha and the up-regulation of the anti-inflammatory gene
IL-10. There was no inhibitory effect of WB and DB on nuclear translocation of NF
kappaB p65. In conclusion, the wild and domesticated basidiocarps of A. rugosum
possessed antioxidant and in vitro anti-inflammatory properties. WB and DB
inhibited downstream inflammatory mediators (TNF-alpha and NO) and induced anti
inflammatory cytokine IL-10 production. No inhibitory effects shown on upstream
nuclear translocation of NF-kappaB p65. WB and DB exhibited antioxidant activity
and attenuation of proinflammatory mediators and therefore, A. rugosum may serve
as a potential therapeutic agent in the management of inflammation.
PMID- 26427055
TI - Accuracy of blood pressure monitors available in high street pharmacies.
AB - The aim of this study was to assess the accuracy of automated blood pressure
monitors on sale to the UK general public. We conducted static pressure accuracy
testing on all compatible (19 out of 22 available) blood pressure monitors
available for sale in pharmacies within the city of Oxford, UK, and tested two
devices for accuracy in measurement of systolic and diastolic blood pressures in
21 adults. The devices showed good accuracy when measuring static pressure in
laboratory bench testing, with the median error per device ranging from -2.2 to
+1.2 mmHg; however, the two devices tested performed worse in vivo than in
laboratory tests, with median errors as high as 6 mmHg. The monitors showed good
accuracy in static pressure testing, with a lack of correlation between monitor
price and accuracy. However, higher error rates seen during in-vivo testing of a
subset of monitors may indicate that static testing may not be appropriate for
routine accuracy assessment of these monitors.
PMID- 26427054
TI - Expression of Mitochondrial Cytochrome C Oxidase Chaperone Gene (COX20) Improves
Tolerance to Weak Acid and Oxidative Stress during Yeast Fermentation.
AB - INTRODUCTION: Saccharomyces cerevisiae is the micro-organism of choice for the
conversion of fermentable sugars released by the pre-treatment of lignocellulosic
material into bioethanol. Pre-treatment of lignocellulosic material releases
acetic acid and previous work identified a cytochrome oxidase chaperone gene
(COX20) which was significantly up-regulated in yeast cells in the presence of
acetic acid. RESULTS: A Deltacox20 strain was sensitive to the presence of acetic
acid compared with the background strain. Overexpressing COX20 using a
tetracycline-regulatable expression vector system in a Deltacox20 strain,
resulted in tolerance to the presence of acetic acid and tolerance could be
ablated with addition of tetracycline. Assays also revealed that overexpression
improved tolerance to the presence of hydrogen peroxide-induced oxidative stress.
CONCLUSION: This is a study which has utilised tetracycline-regulated protein
expression in a fermentation system, which was characterised by improved (or
enhanced) tolerance to acetic acid and oxidative stress.
PMID- 26427056
TI - Structural and Ultrastructural Analysis of the Cervical Discs of Young and
Elderly Humans.
AB - Several studies describing the ultrastructure and extracellular matrix (ECM) of
intervertebral discs (IVDs) involve animal models and specimens obtained from
symptomatic individuals during surgery for degenerative disease or scoliosis,
which may not necessarily correlate to changes secondary to normal aging in
humans. These changes may also be segment-specific based on different load
patterns throughout life. Our objective was to describe the ECM and collagen
profile of cervical IVDs in young (G1 - <35 years) and elderly (G2 - >65 years)
presumably-asymptomatic individuals. Thirty cervical discs per group were
obtained during autopsies of presumably-asymptomatic individuals. IVDs were
analyzed with MRI, a morphological grading scale, light microscopy, scanning
electron microscopy (SEM) and immunohistochemistry (IHC) for collagen types I,
II, III, IV, V, VI, IX and X. Macroscopic degenerative features such as loss of
annulus-nucleus distinction and fissures were found in both groups and
significantly more severe in G2 as expected. MRI could not detect all
morphological changes when compared even with simple morphological inspection.
The loose fibrocartilaginous G1 matrix was replaced by a denser ECM in G2 with
predominantly cartilaginous characteristics, chondrocyte clusters and absent
elastic fibers. SEM demonstrated persistence of an identifiable nucleus and
Sharpey-type insertion of cervical annulus fibers even in highly-degenerated G2
specimens. All collagen types were detected in every disc sector except for
collagen X, with the largest area stained by collagens II and IV. Collagen
detection was significantly decreased in G2: although significant intradiscal
differences were rare, changes may occur faster or earlier in the posterior
annulus. These results demonstrate an extensive modification of the ECM with
maintenance of basic ultrastructural features despite severe macroscopic
degeneration. Collagen analysis supports there is not a "pathologic" collagen
type and changes are generally similar throughout the disc. Understanding the
collagen and ultrastructural substrate of degenerative changes in the human disc
is an essential step in planning restorative therapies.
PMID- 26427057
TI - Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of
the SALL4A Transcription Factor.
AB - All-trans retinoic acid (ATRA) is instrumental to male germ cell differentiation,
but its mechanism of action remains elusive. To address this question, we have
analyzed the phenotypes of mice lacking, in spermatogonia, all rexinoid receptors
(RXRA, RXRB and RXRG) or all ATRA receptors (RARA, RARB and RARG). We demonstrate
that the combined ablation of RXRA and RXRB in spermatogonia recapitulates the
set of defects observed both upon ablation of RAR in spermatogonia. We also show
that ATRA activates RAR and RXR bound to a conserved regulatory region to
increase expression of the SALL4A transcription factor in spermatogonia. Our
results reveal that this major pluripotency gene is a target of ATRA signaling
and that RAR/RXR heterodimers are the functional units driving its expression in
spermatogonia. They add to the mechanisms through which ATRA promote expression
of the KIT tyrosine kinase receptor to trigger a critical step in spermatogonia
differentiation. Importantly, they indicate also that meiosis eventually occurs
in the absence of a RAR/RXR pathway within germ cells and suggest that
instructing this process is either ATRA-independent or requires an ATRA signal
originating from Sertoli cells.
PMID- 26427059
TI - Zipf's Law: Balancing Signal Usage Cost and Communication Efficiency.
AB - We propose a model that explains the reliable emergence of power laws (e.g.,
Zipf's law) during the development of different human languages. The model
incorporates the principle of least effort in communications, minimizing a
combination of the information-theoretic communication inefficiency and direct
signal cost. We prove a general relationship, for all optimal languages, between
the signal cost distribution and the resulting distribution of signals. Zipf's
law then emerges for logarithmic signal cost distributions, which is the cost
distribution expected for words constructed from letters or phonemes.
PMID- 26427058
TI - Postoperative Changes in Aqueous Monocyte Chemotactic Protein-1 Levels and Bleb
Morphology after Trabeculectomy vs. Ex-PRESS Shunt Surgery.
AB - PURPOSE: To evaluate the postoperative changes in blebs and levels of aqueous
monocyte chemotactic protein-1 (MCP-1) after trabeculectomy vs. Ex-PRESS tube
shunt surgery. METHODS: Rabbits were subjected to trabeculectomy or Ex-PRESS tube
shunt surgery and observed for up to 3 months. Intraocular pressure (IOP) was
measured using a rebound tonometer. The MCP-1 level was measured by enzyme-linked
immunosorbent assay (ELISA). Bleb morphology was evaluated using photos and
anterior-segment optical coherence tomography (OCT). RESULTS: There were no
differences in bleb appearance or IOP at any time between the groups. Bleb wall
density in the anterior-segment OCT image was significantly lower 1 week after
surgery in the Ex-PRESS group than the trabeculectomy group. The MCP-1 level in
control eyes was 304.1 +/- 45.2 pg/mL. In the trabeculectomy group, the mean
aqueous MCP-1 level was 1444.9, 1914.3, 1899.8, 516.4, 398.3, 427.3, 609.5,
1612.7, 386.2, and 167.9 pg/mL at 3, 6, and 12 h, and 1, 2, 5, 7, 14, 30, and 90
days after surgery, respectively. In the Ex-PRESS group, the corresponding values
were 1744.0, 1372.0, 932.5, 711.7, 396.1, 487.3, 799.5, 1327.9, 293.6, and 184.0
pg/mL. There were no significant differences in the aqueous MCP-1 level between
the groups at any time point. CONCLUSION: The postoperative changes were similar
in the Ex-PRESS and trabeculectomy groups, except for bleb wall density in the
anterior-segment OCT image. The postoperative aqueous MCP-1 level had bimodal
peaks in both groups.
PMID- 26427060
TI - Design, Synthesis and Evaluation of 2,5-Diketopiperazines as Inhibitors of the
MDM2-p53 Interaction.
AB - The transcription factor p53 is the main tumour suppressor in cells and many
cancer types have p53 mutations resulting in a loss of its function. In tumours
that retain wild-type p53 function, p53 activity is down-regulated by MDM2 (human
murine double minute 2) via a direct protein-protein interaction. We have
designed and synthesised two series of 2,5-diketopiperazines as inhibitors of the
MDM2-p53 interaction. The first set was designed to directly mimic the alpha
helical region of the p53 peptide, containing key residues in the i, i+4 and i+7
positions of a natural alpha-helix. Conformational analysis indicated that 1,3,6
trisubstituted 2,5-diketopiperazines were able to place substituents in the same
spatial orientation as an alpha-helix template. The key step of the synthesis
involved the cyclisation of substituted dipeptides. The other set of
tetrasubstituted 2,5-diketopiperazines were designed based on structure-based
docking studies and the Ugi multicomponent reaction was used for the synthesis.
This latter set comprised the most potent inhibitors which displayed micromolar
IC50-values in a biochemical fluorescence polarisation assay.
PMID- 26427061
TI - Histological and Transcriptomic Analysis of Adult Japanese Medaka Sampled Onboard
the International Space Station.
AB - To understand how humans adapt to the space environment, many experiments can be
conducted on astronauts as they work aboard the Space Shuttle or the
International Space Station (ISS). We also need animal experiments that can apply
to human models and help prevent or solve the health issues we face in space
travel. The Japanese medaka (Oryzias latipes) is a suitable model fish for
studying space adaptation as evidenced by adults of the species having mated
successfully in space during 15 days of flight during the second International
Microgravity Laboratory mission in 1994. The eggs laid by the fish developed
normally and hatched as juveniles in space. In 2012, another space experiment
("Medaka Osteoclast") was conducted. Six-week-old male and female Japanese medaka
(Cab strain osteoblast transgenic fish) were maintained in the Aquatic Habitat
system for two months in the ISS. Fish of the same strain and age were used as
the ground controls. Six fish were fixed with paraformaldehyde or kept in RNA
stabilization reagent (n = 4) and dissected for tissue sampling after being
returned to the ground, so that several principal investigators working on the
project could share samples. Histology indicated no significant changes except in
the ovary. However, the RNA-seq analysis of 5345 genes from six tissues revealed
highly tissue-specific space responsiveness after a two-month stay in the ISS.
Similar responsiveness was observed among the brain and eye, ovary and testis,
and the liver and intestine. Among these six tissues, the intestine showed the
highest space response with 10 genes categorized as oxidation-reduction processes
(gene ontogeny term GO:0055114), and the expression levels of choriogenin
precursor genes were suppressed in the ovary. Eleven genes including klf9, klf13,
odc1, hsp70 and hif3a were upregulated in more than four of the tissues examined,
thus suggesting common immunoregulatory and stress responses during space
adaptation.
PMID- 26427062
TI - Fingerspelling as a Novel Gateway into Reading Fluency in Deaf Bilinguals.
AB - Studies have shown that American Sign Language (ASL) fluency has a positive
impact on deaf individuals' English reading, but the cognitive and cross
linguistic mechanisms permitting the mapping of a visual-manual language onto a
sound-based language have yet to be elucidated. Fingerspelling, which represents
English orthography with 26 distinct hand configurations, is an integral part of
ASL and has been suggested to provide deaf bilinguals with important cross
linguistic links between sign language and orthography. Using a hierarchical
multiple regression analysis, this study examined the relationship of age of ASL
exposure, ASL fluency, and fingerspelling skill on reading fluency in deaf
college-age bilinguals. After controlling for ASL fluency, fingerspelling skill
significantly predicted reading fluency, revealing for the first-time that
fingerspelling, above and beyond ASL skills, contributes to reading fluency in
deaf bilinguals. We suggest that both fingerspelling--in the visual-manual
modality--and reading--in the visual-orthographic modality--are mutually
facilitating because they share common underlying cognitive capacities of word
decoding accuracy and automaticity of word recognition. The findings provide
support for the hypothesis that the development of English reading proficiency
may be facilitated through strengthening of the relationship among
fingerspelling, sign language, and orthographic decoding en route to reading
mastery, and may also reveal optimal approaches for reading instruction for deaf
and hard of hearing children.
PMID- 26427063
TI - Intrinsic Multi-Scale Dynamic Behaviors of Complex Financial Systems.
AB - The empirical mode decomposition is applied to analyze the intrinsic multi-scale
dynamic behaviors of complex financial systems. In this approach, the time series
of the price returns of each stock is decomposed into a small number of intrinsic
mode functions, which represent the price motion from high frequency to low
frequency. These intrinsic mode functions are then grouped into three modes,
i.e., the fast mode, medium mode and slow mode. The probability distribution of
returns and auto-correlation of volatilities for the fast and medium modes
exhibit similar behaviors as those of the full time series, i.e., these
characteristics are rather robust in multi time scale. However, the cross
correlation between individual stocks and the return-volatility correlation are
time scale dependent. The structure of business sectors is mainly governed by the
fast mode when returns are sampled at a couple of days, while by the medium mode
when returns are sampled at dozens of days. More importantly, the leverage and
anti-leverage effects are dominated by the medium mode.
PMID- 26427066
TI - [Evidence-based practice guidelines for standardized pathological diagnosis of
primary liver cancer in China: 2015].
PMID- 26427064
TI - Comparisons of the Effects of Elevated Vapor Pressure Deficit on Gene Expression
in Leaves among Two Fast-Wilting and a Slow-Wilting Soybean.
AB - Limiting the transpiration rate (TR) of a plant under high vapor pressure deficit
(VPD) has the potential to improve crop yield under drought conditions. The
effects of elevated VPD on the expression of genes in the leaves of three soybean
accessions, Plant Introduction (PI) 416937, PI 471938 and Hutcheson (PI 518664)
were investigated because these accessions have contrasting responses to VPD
changes. Hutcheson, a fast-wilting soybean, and PI 471938, a slow-wilting
soybean, respond to increased VPD with a linear increase in TR. TR of the slow
wilting PI 416937 is limited when VPD increases to greater than about 2 kPa. The
objective of this study was to identify the response of the transcriptome of
these accessions to elevated VPD under well-watered conditions and identify
responses that are unique to the slow-wilting accessions. Gene expression
analysis in leaves of genotypes PI 471938 and Hutcheson showed that 22 and 1
genes, respectively, were differentially expressed under high VPD. In contrast,
there were 944 genes differentially expressed in PI 416937 with the same increase
in VPD. The increased alteration of the transcriptome of PI 416937 in response to
elevated VPD clearly distinguished it from the other slow-wilting PI 471938 and
the fast-wilting Hutcheson. The inventory and analysis of differentially
expressed genes in PI 416937 in response to VPD is a foundation for further
investigation to extend the current understanding of plant hydraulic conductivity
in drought environments.
PMID- 26427065
TI - Evaluation of LiF:Mg,Ti (TLD-100) for Intraoperative Electron Radiation Therapy
Quality Assurance.
AB - BACKGROUND: Purpose of the present work was to investigate thermoluminescent
dosimeters (TLDs) response to intraoperative electron radiation therapy (IOERT)
beams. In an IOERT treatment, a large single radiation dose is delivered with a
high dose-per-pulse electron beam (2-12 cGy/pulse) during surgery. To verify and
to record the delivered dose, in vivo dosimetry is a mandatory procedure for
quality assurance. The TLDs feature many advantages such as a small detector size
and close tissue equivalence that make them attractive for IOERT as in vivo
dosimeters. METHODS: LiF:Mg,Ti dosimeters (TLD-100) were irradiated with
different IOERT electron beam energies (5, 7 and 9 MeV) and with a 6 MV
conventional photon beam. For each energy, the TLDs were irradiated in the dose
range of 0-10 Gy in step of 2 Gy. Regression analysis was performed to establish
the response variation of thermoluminescent signals with dose and energy.
RESULTS: The TLD-100 dose-response curves were obtained. In the dose range of 0
10 Gy, the calibration curve was confirmed to be linear for the conventional
photon beam. In the same dose region, the quadratic model performs better than
the linear model when high dose-per-pulse electron beams were used (F test;
p<0.05). CONCLUSIONS: This study demonstrates that the TLD dose response, for
doses <=10 Gy, has a parabolic behavior in high dose-per-pulse electron beams.
TLD-100 can be useful detectors for IOERT patient dosimetry if a proper
calibration is provided.
PMID- 26427067
TI - [Percutaneous transhepatic variceal embolization followed with partial splenic
embolization for the acute variceal massive hemorrhage in cirrhosis].
PMID- 26427068
TI - [Clinical study on the risk factors of severe hepatitis with nosocomial fungal
infection].
PMID- 26427069
TI - [Evaluation of the safety of granulocyte colony-stimulating factor subcutaneous
injection as treatment for HBV-related acute on chronic liver failure].
PMID- 26427070
TI - [Prevalence of nutritional risk factors and malnutrition among inpatients with
fever diseases in Tianjin].
PMID- 26427071
TI - [Performance evaluation of the IS1200 domestic chemiluminescence analyzer for
detecting hepatitis B virus serum markers].
PMID- 26427072
TI - [A case report of overlapping Rosai-Dorfman disease of the liver and gallbladder
combined with hepatocellular adenoma].
PMID- 26427074
TI - [Obstructive sleep apnea hypopnea syndrome and nonalcoholic fatty liver disease].
PMID- 26427073
TI - [Observational research is an important accompaniment to randomized and
controlled clinical studies].
PMID- 26427075
TI - [Hepokines in metabolic diseases].
PMID- 26427076
TI - [Progress in the clinical and basic research of liver fibrosis].
PMID- 26427077
TI - [Diagnose the regression of liver fibrosis and cirrhosis].
PMID- 26427078
TI - [Researches on the prevention and treatment of bleeding gastroesophageal varices
secondary to portal hypertension in patients with cirrhosis].
PMID- 26427080
TI - [Efficacy and safety of Fuzhenghuayu capsule for treating liver fibrosis in
patients with chronic hepatitis B: a meta-analysis].
PMID- 26427079
TI - [Diffraction-enhanced imaging and in-line phase contrast imaging with synchrotron
radiation for human intra-hepatic bile duct dilation ex vivo].
PMID- 26427081
TI - [Potential values for diagnosis and assessment of nonalcoholic fatty liver
disease staging using Gd+-EOB-DTPA-enhanced MRI].
PMID- 26427082
TI - [Expression and prognostic significance of cyclin kinase subunit 1 in human
hepatocellular carcinoma].
PMID- 26427083
TI - [Clinical analysis of Fanconi syndrome induced by adefovir dipivoxil].
PMID- 26427084
TI - [Report of the Sixth Symposium on the Hotspots and Challenges in Research of
Antiviral Therapy for Chronic Hepatitis B and Chronic Hepatitis C].
PMID- 26427085
TI - [Rules of lipotoxicity and lipoapoptosis in the pathogenesis of alcoholic fatty
liver disease].
PMID- 26427086
TI - [Polymorphisms in the PNPLA3 gene are associated with hepatocellular carcinoma].
PMID- 26427087
TI - [Acquired hepatocerebral degeneration: a rare liver-related neurological
disorder].
PMID- 26427088
TI - [Advances in diagnosis and management of adult-onset type II citrullinemia
(CTLN2)].
PMID- 26427089
TI - Gertrude H. Lamb, 1918-2015, AHIP, FMLA.
PMID- 26427090
TI - Observing the human condition.
PMID- 26427091
TI - Better concordance for interphalangeal depth ratio than Schamroth's sign or
hyponychial angle for diagnosis of digital clubbing.
PMID- 26427092
TI - Patients' perspectives on the delivery of hepatitis B management and care.
PMID- 26427093
TI - Developing a care model for hospice and palliative nurses. Reply.
PMID- 26427094
TI - [History of Japanese Kampo Medicines Manufacturers].
PMID- 26427095
TI - [History of Inorganic-pharmaceutics in Japan].
PMID- 26427096
TI - [Transition of Psychotropic Drugs in Japanese Pharmacopoeia (JP) (Part 15).
Transitions in the Standards and Test Methods of Potassium Bromide in JP I (1886)
and JP X VI (2011), and Comparison between the USP and BP].
AB - In mental clinics, bromide agents such as potassium bromide were often once used
as therapeutic drugs to treat psychiatric disorders. They were also given as
hypnotic, sedative and antiepileptic medicines. However, the appearance of new
medicines has resulted in them not being used for these purposes in recent years.
Potassium bromide is still continuously listed in today's JP and BP. This
suggests that it maintains value as a basic medicine for treating mental
disorders in the history of psychotropic medicines. However, regarding the
standards and test methods for potassium bromide in the present JP, as a result
of a comparison between the USP of the same age, BP and EP, a gap is seen, and
this is very regrettable. The exchange of art and scientific information related
to medical sciences with foreign countries is becoming more active today.
Therefore, scholarly information overseas should be collected and reflected in
the standards and test methods for potassium bromide adopted in the JP of Japan.
The author believes that the standards and test methods comparable to those at
the international level should introduced. On the other hand, potassium bromide
was recetnly relisted by USP29 (2006) for the first time in approximately 50
years. Moreover, instrumental analysis was introduced as part of the test methods
in BP2013; that is, an epoch-making revision was made in terms of test methods.
It is assumed from this that there is a sign of new change regarding the
existence of potassium bromide as hypnotic, sedative and antiepileptic medicines,
and its utility value. It is believed that the sign of change in view of the
utility value and pharmacological evaluation probably arose with the new clinical
knowledge that potassium bromide was used to treat a baby seriously ill with
myoclony epilepsy, as well as to treat a dog with epilepsy.
PMID- 26427097
TI - [Element Analysis of a Chinese Yagen Bearing the Inscription of "Product of the
Ming-Zhengde Period" [Property of the Naito Memorial Museum of Pharmaceutical
Science and Industry, Gifu] using an X-ray Fluorescence Spectrometer].
AB - Yagen (see text) is an oriental grinder for crude plant medicines. It consists of
a disk and navicular mortar. A Chinese yagen with the inscription, "Product of
the Ming-Zhengde Period (See text), (1506-1521 A.D.)" has been housed for 40
years in the Naito Memorial Museum of Pharmaceutical Science and Industry
(Kakamigahara, Gifu Prefecture, Japan). To identify the district that produced
this yagen, the authors analyzed the elements using an X-ray fluorescence
spectrometer. The results showed that the blue design and blue Chinese characters
on the yagen were enameled with elements of cobalt, manganese, and iron.
Therefore, it is believed that the yagen was made in an old porcelain kiln near
Zhangzhou in Fujian Province, China. However, as the period of production could
not determined in the present study, further research is needed in the future.
PMID- 26427098
TI - [Herbological Study on the Medicinal Effects of Roasted Licorice and Honey
roasted Licorice].
AB - In China, the crude drug licorice ("kanzo" in Japanese, "gancao" in Chinese) has
been used both dried and roasted as the situation demands from ancient times. The
meaning of "roasted licorice" is simply roasted and honey-roasted in ancient and
modern times, respectively. However, it is not clear medicinal purposes of
processed licorice or why licorice processed with honey began to be used. We
researched ancient literature and found that the main objective of roasting was
to change the property of licorice from cool to warm (i.e., dried licorice had
the effect of draining fire), while roasted licorice was used as an energy
supplement, having a digestive effect and thus warming the body. Meanwhile,
doctors began using honey-roasted licorice to treat throat pain from the Song
dynasty, and then at the end of the Qing dynasty, honey-roasted licorice was
expected to have the same effects of roasted licorice (i.e., supplementing energy
and having a digestive effect).
PMID- 26427099
TI - [Tri-phala (Three Myrobalans) as Described in the Second Part of the Bower
Manuscript, the Navanitaka].
AB - In India, since ancient times Tri-phala (meaning "three fruits" in Sanskrit) has
been considered to be a combination of the following fruits: -Haritaki
(Terminalia chebula, Retz.), Amalaka (Embelica officinalis Gaertn), and Vibhitaka
(Terminalia belerica Roxb.). These plants are also listed in the Ayurvedic
Pharmacopoeia of India. Haritaki and Amalaka have also been used for medicinal
purposes since ancient times in Japan under the Japanese names of (see text)
(Kariroku) and (see text) (Annmaroku), respectively. Both have been carefully
preserved as treasured drugs in the nationally important Shosoin treasure
storehouse. This study attempts to clarify the description of Tri-phala in the
Navanitaka, which is the second part of the Bower Manuscript (Bower Ms.), and
examines the reasons why these plants were combined. This paper begins with a
summary description of Tri-phala in the context of traditional Asian medicine,
followed by the delineation of drug selection principles in Ayurveda. Tri-phala
formulas in the Navanitaka are then examined. The Carakasamhita (CS) treats Tri
phala as a purifier and tonic (rasayana), describing it as a formula for
rejuvenation and longevity. On the other hand, the Susrutasamhitd (SS) regards
Tri-phala as having the efficacy of balancing kapha (phlegm) and pitta (bile),
and also as being a medicine to promote excretion and enhance digestive functions
for better nutritional intake. It is described to have an effect of curing
diseases by keeping the tridhau (theree element) valance. Tri-phala is thus used
as an ingredient of laxatives for diseases that result from kapha imbalance and
tonic. The Astangahrdayasamhita (AHS) considers Tri-phala to have a particular
superiority among cure-all medicines with the power to dispel illness. It
controls kapha and overcomes blood diseases. Tri-phala formulas found in the
Navanitaka were prescribed for the treatment of abdominal tumors induced by vayu
(wind) disorder as well as for coughs caused by pitta and kapha disorder. Tri
phala was also administered to facilitate nutrient absorption, regulate bowel
function, and promote excretion. Tri-phala thus restores the balance of tridhau
by facilitating water distribution in the body. For these reasons, the optimal
combination of Tri-phala was then established to adjust kapha for most efficient
purification effects.
PMID- 26427100
TI - [Twenty-year History and Future Challenges in Transparency Enhancement of Review
Process for Approval: Focus on Public Release of Review Reports regarding New
Drugs and Medical Devices].
AB - For 20 years, the Ministry of Health, Labour and Welfare (MHLW, formerly Ministry
of Health and Welfare (MHW)) has been trying to increase transparency of the
review process for approving reports in order to promote the rational use of
newly approved drugs and medical devices. The first Summary Basis of Approval
(SBA) was published by MHW in 1994. In 1999, evaluation reports were prepared by
MHW and the Pharmaceuticals and Medical Devices Evaluation Center to make them
available to the public. In 2005, a notice from the Chief Executive of the
Pharmaceuticals and Medical Devices Agency (PMDA) made procedures for public
release of information on reviewing applications for new drugs. In 2006, 90
review reports of newly approved drugs and eight medical devices were revealed on
PMDA websites. The dissemination of information by the United States Food and
Drug Administration (FDA) and that of the European Medicines Agency (EMA) were
studied and compared with that of the MHLW and PMDA. While common technical
documents (CTD) for new drugs and summary technical documents (STED) for new
medical devices have been released by PMDA, such documents are not released by
the FDA and EMA. The European Public Assessment Report (EAPR) summary for the
public is an interesting questionnaire approach that uses the "What," "How" and
"Why" format. Finally, future proposals for the next decade are also outlined.
PMID- 26427101
TI - [The Original Formulation for Toso-shu (Tusujiu), Created by the 3rd Century
Chinese Physician, Hua Tuo].
AB - The original formulation for "Tusujiu," which Japanese people still consume on
the morning of January 1st, was created by Hua Tuo, but has not been studied in
detail. The book Huatuo Shenyi Bizhuan, found in 1918, describes a concoction,
"Biyijiu," that shows great similarity to the current Tusujiu; the ingredients
for Biyijiu being rhubarb, atractylodes rhizome, cinnamon bark, platycodon root,
zanthoxylum fruit, processed aconite root and smilax rhizome. The procedures for
preparing and drinking it are to "pound the ingredients and then put them into a
silk bag dyed with madder. During the daytime of the last day of the year, hang
the bag in a well to soften the powder. Take the bag out early in the morning of
the next day, the first day of the year. Heat the bag in fermented liquor until
simmering. Drink the liquid with all family members, doing so while facing east.
If one person drinks it, there will be no disease in the family. If the whole
family drinks it, there will be no disease in their neighborhood in an area of
one square 'li'. In this study, to determine the original formulation for
Tusujiu, we examined a number of ancient medical texts from the 3rd to the 13th
century that discuss Biyijiu and Tusujiu. As a result, we concluded that
"Biyijiu" is likely to be the original formulation developed by Hua Tuo.
PMID- 26427102
TI - [Pharmaceutical Regulations in the Japanese Hospitals in 1880s and the Case of a
Scholar of Pharmacology in Oita Prefecture].
AB - In the 1870s, various provisions existed regarding pharmacists working at
Japanese military hospitals. And in the decade of the 1880s, some hospitals in
Tokyo and Oita implemented them. These provisions gave pharmacists the right to
challenge doctors' prescriptions and provide patients with medicine-related
information. In Oita Prefecture, patients could have their prescriptions filled
outside of the hospital. This paper examines the case of one scholar of
pharmacology who worked in Oita Medical School Hospital.
PMID- 26427103
TI - [Visualization for Traditional Quality Management Techniques--Characterization
Method for Spikenard of INUBUSHI SEIYAKU Established in the Edo Period].
AB - INUBUSHI SEIYAKU, a Japanese pharmaceutical company established in 1807,
manufactures KEISHIN-TAN. This is an original drug developed by the company, and
consists of 14 exotic natural medicines, spikenard, oriental bezoar, musk,
agarwood, etc. It has been used for adjusting the autonomic nervous system and
physical conditions. We studied the original methods of the traditional quality
management techniques handed down within INUBUSHI SEIYAKU in selecting the
appropriate spikenard (Nardostachys chinensis) for medicinal use. Currently,
spikenards are mainly used as incense rather than medicine. KEISHIN-TAN is a rare
case in that the bulk powder of the spikenards is used for pharmaceutical
products in Japan. We examined the morphological characteristics and made an
analysis of the component of spikenards selected by traditional methods. The raw
material of the spikenards was purchased from the Japanese market, and was
classified into two categories-superior, fit for medicinal use and defective, to
be discarded-by traditional methods of INUBUSHI SEIYAKU. The methods of the
characterization of the spikenard by INUBUSHI SEIYAKU were investigated. As a
result, only thick spikenard roots over 2.0 cm in length and approximately 0.5 cm
in diameter were found to be used, and the total weight of the superior was only
15% of the raw material. By comparing the weights of hexane extracts and GC-MS
analyses, the content of calarene--main sedative compound in spikenards--in the
superior material was 2.8 times higher than the raw material and 4.3 times higher
than the defective material. The ways to devise how to enhance the
pharmacological effects of spikenards may be contained in this method. These
results revealed the traditional spikenard selection criteria, and may show the
indications of using spikenard or its compounds for medicinal purposes.
PMID- 26427104
TI - Effect of Aidi injection plus chemotherapy on gastric carcinoma: a Meta-analysis
of randomized controlled trials.
AB - OBJECTIVE: To conduct a Meta-analysis of studies on the effect of Aidi injection
combined with chemotherapy versus chemotherapy alone in the treatment of gastric
cancer (GC). METHODS: Nine electronic databases and six gray literature databases
were comprehensively searched until April 20, 2013. Two reviewers independently
selected and assessed included trials according to the inclusion and exclusion
criteria. The risk of bias tool from the Cochrane Handbook version 5.1.0 was used
to assess trial quality. All calculations were performed using Review Manager
5.0. RESULTS: Thirty-two studies including 1927 participants met the inclusion
criteria, most of which were low quality. Compared with chemotherapy alone, Aidi
injection plus the same chemotherapy significantly improved the effective rate
[OR = 1.52, 95% CI (1.24, 1.86), P < 0.0001], clinical beneficial rate [OR =
1.77, 95% CI (1.33, 2.36), P < 0.0001], and quality of life [OR = 3.02, 95% CI
(2.39, 3.82), P < 0.000 01]. There was a significant improvement in nausea and
vomiting incidence [OR = 0.34, 95% CI (0.24, 0.47), P < 0.000 01], diarrhea [OR =
0.47, 95% CI (0.33, 0.69), P < 0.000 01], leukopenia (III-IV) [OR = 0.34, 95% CI
(0.23, 0.51), P = 0.05], hemoglobin decrease (III-IV) [OR = 0.42, 95% CI (0.18
1.00), P = 0.05], thrombocytopenia (III-IV) [OR = 0.46, 95% CI (0.22, 0.96), P =
0.04], and damage to liver function [OR = 0.36, 95% CI (0.24, 0.54), P <
0.00001]. CONCLUSION: Aidi injection combined with chemotherapy significantly
improved the clinical effect of chemotherapy, reducing the incidence of adverse
events. Use of the CONSORT statement for randomized controlled trials is
recommended for stricter reporting.
PMID- 26427105
TI - Effect of Sancaijiangtang on plasma nitric oxide and endothelin-1 levels in
patients with type 2 diabetes mellitus and vascular dementia: a single-blind
randomized controlled trial.
AB - OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric
oxide and endothelin-1 levels. We sought to identify the common pathological link
and mechanism of action for Traditional Chinese medicine in type 2 diabetes
mellitus and vascular dementia, and to explicate the material basis for treating
the different diseases with the same method in Traditional Chinese Medicine.
METHODS: In total, 168 patients with type 2 diabetes mellitus and vascular
dementia were enrolled in the study, and randomly divided into two groups by
simple randomization. Patients in the treatment group received oral
Sancaijiangtang powders with pioglitazone hydrochloride three times daily, while
patients in the control group received pioglitazone hydrochloride alone. The
treatment course was for 12 weeks. Mini-mental state examinations (Chinese
version) and Montreal Cognitive Assessments (Beijing version) were performed, and
fasting plasma glucose, fasting insulin, hemoglobin A1c, homeostasis model
assessment of insulin resistance, plasma nitric oxide and endothelin-1 levels
were measured before and after the treatment. RESULTS: The post-treatment levels
for all measurements in both groups were better than pre-treat- ment levels (P <
0.05). The post-treatment levels for all measurements in the treatment group were
better than the levels measured in the control group (P < 0.05). CONCLUSION: Type
2 diabetes mellitus and vascular dementia have common pathological mechanisms for
insulin resistance and endothelium dysfunction. Sancaijiangtang powders could
improve the release of nitric oxide and inhibit the secretion of endothelin-1.
Therefore, the material basis exists for treating the different diseases with the
same method in Traditional Chinese Medicine.
PMID- 26427106
TI - Efficacy of Zhenjingdingzhi decoction in treating insomnia with Qi-deficiency of
heart and gallbladder: a randomized, double-blind, controlled trial.
AB - OBJECTIVE: To evaluate the clinical efficacy of Zhenjingdingzhi decoction in
treating insomnia with Qi-deficiency of heart and gallbladder. METHODS: We
conducted a double-blind, randomized, controlled trial involving 100 patients
with insomnia of Qi-deficiency of heart and gallbladder. Patients were randomly
divided into the treatment group (n = 50) and the control group (n = 50)
according to a random number table. The treatment group was given Zhenjingdingzhi
decoction, while the control group was treated with Suanzaoren decoction. The
pharmacological treatment lasted for 8 weeks. The clinical efficacy was assessed
by using Spiegel scale, Pittsburgh sleep quality index (PSQ) and Traditional
Chinese Medicine (TCM) syndrome scores. RESULTS: Comparing Spiegel scores between
the two groups at 4 and 8 weeks, the differences in curative effect between the
two groups were both significant (both P < 0.05). The total effective rate was
46% in the treatment group and 27.7% in the control group at 4 weeks, and 80% and
53.2% at 8 weeks, respectively; After 8 weeks, PSQI scores showed that the total
effective rates differed significantly between the two groups (P < 0.01): 84% in
the treatment group and 59.6% in the control group; In improving sleep quality
and sleep duration, the curative effect of the treatment group was better than
that of the control group (P < 0.05). TCM syndrome, especially insomnia and
palpitation, was improved better in the treatment group after 8 weeks as compared
to that in the control group (P < 0.05). The total effective rate of the two
groups was 84% and 66%, respectively. CONCLUSION: Zhenjingdingzhi decoction is
effective and safe for the treatment of insomnia with Qi-deficiency of heart and
gallbladder, especially for improving sleep quality and sleep duration.
PMID- 26427107
TI - Effect of Shoushen granule on arterial elasticity in patients with carotid
atherosclerosis: a clinical randomized controlled trial.
AB - OBJECTIVE: To investigate the effectiveness of Shoushen granule, Chinese herbal
preparation, on carotid artery elasticity in patients with carotid
atherosclerosis. METHODS: The total of 156 carotid atherosclerosis patients were
randomly divided into the intervention group (83 cases, treated with Shoushen
granule) and the control group (73 cases, treated with pravastatin). Brachial
ankle pulse wave velocity baPWV) and Ankle-Brachial Pressure Index (ABI) were
measured by automated arteriosclerosis detector. The changes of common carotid
artery intima-media thickness (IMT) and parameters of the carotid artery
elasticity in patients, including stiffness parameter (beta), pressure-strain
elastic modulus (Ep), arterial compliance (Ac), augmentation index (AI), and
pulse wave velocity (PWV) were detected by Echo-Tracking (ET) technique before
and after 24 week treatment. In the meantime, levels of blood lipid, and liver
and renal function were measured respectively. RESULTS: After 24 weeks, baPWV, MT
and parameters of the carotid artery elasticity (beta, Ep, AI and PWVbeta) were
markedly decreased in intervention group compared with those of before treatment
(P < 0.01), but the level of Ac was increased significantly (P < 0.01). And there
were no significant differences compared with control group on the same period (P
> 0.05). CONCLUSION: In this pilot study, it was demonstrated ET technology and
automated arteriosclerosis detector could be used to evaluate carotid artery
elasticity effectively, and the action of Shoushen granule on carotid
atherosclerosis might be related to the regulation of carotid artery elasticity.
PMID- 26427108
TI - Impact of classic massage on blood pressure in patients with clinically diagnosed
hypertension.
AB - OBJECTIVE: To assess the impact of classic massage on the changes in the values
of blood pressure in women with previously diagnosed hypertension. METHODS: The
study involved a group often women aged 60-68, who had previously been diagnosed
with hypertension. Ten sessions of classic massage of the lower limbs were
performed on the subjects. The massage sessions were conducted every day over ten
consecutive days. Throughout the treatment, the subjects' blood pressure was
measured using a manometer with a stethoscope TRO-CARDIO KIT 2 MONO. Their blood
pressure was taken 1 min before the massage, as well as 1 min and 5 min after
each session. The study took place between March and June 2013 in Szpital
Specjalistyczny im. Jedrzeja Sniadeckiego (Jedrzej Sniadecki Specialist Hospital)
in Nowy Sacz, at the Department of Internal Diseases. RESULTS: For ten
consecutive days, the blood pressure values in the examined women were
decreasing, with the exception of the diastolic blood pressure measured 5 min
after the massage. CONCLUSION: The drops in blood pressure by several percent,
noted in the majority of the female subjects over the time of the study. Classic
massage might provide a safe supportive measure in pharmacologic treatment of
hypertension.
PMID- 26427109
TI - Comparative effect of electroacupuncture and moxibustion on the expression of
substance P and vasoactive intestinal peptide in patients with irritable bowel
syndrome.
AB - OBJECTIVE: To compare the impacts of electroacu puncture (EA) and moxibustion
(Mox) on the prima ry gastrointestinal symptoms and the expressions of colonic
mucosa-associated neuropeptide substance P (SP) and vasoactive intestinal peptide
(VIP) in patients with either diarrhea-predominant or constipation-predominant
irritable bowel syndrome (IBS-D and IBS-C, respectively). METHODS: Eighty-five
IBS patients were randomly allocated to the EA and Mox groups. Zusanli (ST 36)
and Shangjuxu (ST 37) were selected as acupoints for electroacupuncture or warm
moxibustion treatment once a day for 14 consecutive days. Before and after the
treatment sessions, a Visual Analog Pain Scale and the Bristol Stool Form Scale
were used to evaluate gastrointestinal symptoms. There were four dropout cases,
leaving 81 participants (41 with IBS-D and 40 with IBS-C) who volunteered to
undergo colonoscopy before and after the treatment sessions. During colonoscopy,
sigmoid mucosa were collected to detect SP and VIP expression using
immunohistochemistry assay. RESULTS: Both EA and Mox treatments were effective at
relieving abdominal pain in IBS-D and IBS-C patients. However, Mox was more
effective at reducing diarrhea in IBS-D patients, whereas EA was more effective
at improving constipation in IBS-C patients. EA and Mox treatments both down
regulated the abnormally increased SP and VIP expression in the colonic mucosa,
with no significant difference shown between the two treatments. CONCLUSION: Both
EA and Mox treatments are effective at ameliorating gastrointestinal symptoms by
reducing SP and VIP expression in the colonic mucosa of IBS patients.
PMID- 26427110
TI - Gait analysis of patients with knee osteoarthritis before and after Chinese
massage treatment.
AB - The objective of this study was to evaluate the effectiveness of Chinese massage
therapy in patients with knee osteoarthritis (OA) by measuring lower-limb gait
parameters. We recruited 20 women with knee OA, who then underwent Chinese
massage therapy three times per week for 2 weeks. The patients underwent gait
evaluation using a six-camera infrared motion analysis system. They completed
Western Ontario and McMaster Universities Osteoarthritis Index questionnaires
before and after treatment. We calculated the forward speed, step width, step
length, total support time percentage, initial double support time percentage,
and single support time percentage. We also measured the angles at the knee, hip,
and ankle during the stance phase of walking. The results showed statistically
significant mean differences in knee pain relief, alleviation of stiffness, and
physical function enhancement after therapy (P < 0.05). The patients gained
significantly faster gait speed, greater step width, and increased total support
time percentage after the Chinese massage therapy (P < 0.05). There were no
significant differences in the range of motion or initial contact angles of the
knee, hip, or ankle during the stance phase of walking. We concluded that Chinese
massage is a beneficial complementary treatment and an alternative therapy choice
for patients with knee OA for short-term pain relief. Chinese massage may improve
walking ability for these patients.
PMID- 26427111
TI - Effect of Huqian Wan on liver-Yin and kidney-Yin deficiency patterns in patients
with knee osteoarthritis.
AB - OBJECTIVE: To observe the curative effect of Huqian Wan on liver and kidney-Yin
deficiency knee osteoarthritis (KOA). METHODS: One hundred patients were randomly
divided, into a treatment (50 patients) and control group (50 patients). In the
treatment group, patients orally took the Chinese medicine Huqian Wan. Control
group patients orally took Votalin, 75 mg, once a day, for 8 weeks. The visual
analog scale (VAS), Western Ontario and McMaster University Osteoarthritis Index
(WOMAC), and Medical Outcomes Study Short Form 36-Item Health Survey (SF 36) were
used to evaluate the curative effect before treatment and after 8 and 16 weeks of
treatment. RESULTS: VAS and WOMAC scores significantly decreased and SF 36 scores
significantly increased after treatment in both groups compared with before
treatment (P < 0.05). There were significant differences in VAS, WOMAC, and SF 36
score changes between the two groups at week 16 (P < 0.05). There was a
significant increase in VAS and WOMAC scores in the control groups (P < 0.05)
between weeks 8 and 16, but no significant difference was found in the treatment
group (P > 0.05). CONCLUSION: Huqian Wan could effectively improve the clinical
symptoms and quality of life in patients with KOA. It could also have a better
and longer lasting curative effect without obvious adverse events compared with
Votalin.
PMID- 26427112
TI - Effect of Dongchongxiacao (Cordyceps) therapy on contrast-induced nephropathy in
patients with type 2 diabetes and renal insufficiency undergoing coronary
angiography.
AB - OBJECTIVE: To study the protective effects of Dongchongxiacao (Cordyceps) (DCXC)
on contrast-induced nephropathy (CIN) in patients with type 2 diabetes and renal
insufficiency undergoing coronary angiography. METHODS: A total of 120 patients
with type 2 diabetes whose estimated glomerular filtration rater (eGFR) was 60
mL/min . 1.73 in2, were divided randomly into three groups, basic treatment group
(n = 41), standard DCXC therapy group (n = 39, 2-g corbrin capsules, 3 times/d, 3
days before and after angiography), and intensive DCXC therapy group (n = 40, 3-g
corbrin capsules, 3 times/d, 3 days before and after angiography). Serum
creatinine (cr) and eGFR were assessed at the time of admission to hospital, and
on days 1, 2 and 3 after angiography. Urine neutrophil-gelatinase-associated-lipo
calin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) were
measured before angiography and at day 1 after angiography for all patients. The
primary end point was the prevalence of CIN. The secondary end point was a 25% or
greater reduction in eGFR. RESULTS: CIN occurred in 11 of 120 patients (9.17 %).
The prevalence of CIN was lower in the DCXC treatment groups than in the basic
treatment group (P < 0.05), with a more significant decrease in the prevalence of
CIN in the intensive DCXC therapy group (P < 0.01). Compared with the basic
treatment group, a lower proportion of patients in the DCXC treatment groups had
an eGFR decrease of 25% or greater (P < 0.05); patients with an eGFR decrease of
25% or greater accounted for an even lower proportion in the intensive DCXC
therapy group (P < 0.01). Within 1 day of the procedure, urine levels of KIM-1,
NGAL and IL-18 in patients in the intensive DCXC therapy group were lower than
those in the basic treatment group and standard therapy group (P < 0.05).
CONCLUSION: DCXC treatment may protect against CIN in patients with type 2
diabetes and renal insufficiency undergoing coronary angiography, with intensive
DCXC therapy being more effective.
PMID- 26427113
TI - Effect of traditional Chinese comprehensive therapy on gestation in patients with
previously failed in vitro fertilization and embryo transfer.
AB - OBJECTIVE: To explore the effect of traditional Chinese comprehensive therapy
(TCCT) on promoting gestation in patients with previously failed in vitro
fertilization and embryo transfer (IVF-ET) because of kidney deficiency, liver
stagnation, and blood stasis (KLB). METHODS: Sixty-seven patients were enrolled
in this study and divided into two groups: a trial group with 35 patients and a
control group with 32 patients. The trial group was given TCCT for 3 months, then
administered IVF-ET or awaited natural pregnancy. The control group was
administered IVF--ET without TCCT 3 months after the previous IVF-ET or natural
pregnancy attempt. The patterns of KLB were observed both before and after
treatment. The natural pregnancy rate of the two groups was calculated after
treatment. Differences between the two groups were compared after using IVF-ET
treatment again in fertilized egg number and fertilization rate were evaluated.
RESULTS: After treatment with TCM comprehensive therapy, seven patients in the
treatment group became pregnant, while there were no successful conceptions in
the control group. The difference in clinical pregnancy rate in the initial cycle
and transfer cycle of IVF were significantly different (P < 0.05). The trial
group had a significantly higher conception rate than that of the control group
(P < 0.05). CONCLUSION: TCCT can promote the natural pre nancy rate in patients
with previously failed IVF-ET. TCCT could increase patients' fertilized egg
number, fertilization rate, pregnancy rate, and clinical pregnancy rate after
another IVF-ET treatment.
PMID- 26427114
TI - Effect of Chaiqinchengqi decoction on inositol requiring enzyme 1alpha in
alveolar macrophages of dogs with acute necrotising pancreatitis induced by
sodium taurocholate.
AB - OBJECTIVE: To investigate the effect of Chaiqinchengqi decoction (CQCQD) on
inositol requiring enzyme lalpha (IRElalpha) in alveolar macrophages (AMs) of the
dog model of acute necrotising pancreatitis (ANP) induced by sodium taurocholate.
METHODS: Fifteen beagle dogs were randomised into a control group, ANP group and
CQCQD group (n = 5 per group). ANP was induced by a retrograde duct injection of
50 mg/kg of 5% sodium taurocholate. The dogs in the control group received
injections of the same volume of saline as the sodium taurocholate. After the
models were induced, the dogs in the CQCQD group were administered 10 mL/kg CQCQD
every 2 h for 6 h. Two hours after the last administration of either CQCQD or
saline, they were sacrificed by anaesthesia. AMs were collected to determine the
IRElalpha and interleukin-1beta (IL-1beta) mRNA and protein expression, and
pancreatic tissues were collected for histopathology analysis. RESULTS: Compared
with the ANP group, the mRNA and protein expression of IREl a and the protein
expression of IL-1beta of AMs in the CQCQD group were significantly down
regulated, and the pancreatic histopathology score of the CQCQD group also was
lower. There was no significant difference in the mRNA expression of IL-1beta of
AMs between the two groups. CONCLUSION: The CQCQD-induced down-regulation of the
IL-1beta protein expression may involve the down-regulation of the mRNA and
protein expression of IRElalpha in AMs.
PMID- 26427115
TI - Ginsenoside Rg3 inhibits colon cancer cell migration by suppressing nuclear
factor kappa B activity.
AB - OBJECTIVE: To study the mechanism of the inhibitory effect of ginsenoside Rg3 on
colon cancer cell migration. METHODS: Transwell migration assays were performed
to investigate the inhibitory effect of ginsenoside Rg3 on SW480 cell migration.
Electrophoretic mobility shift assays (EMSAs) and dual luciferase reporter assays
were used to study the suppression capability of Rg3 on nuclear factor kappa B
(NF-kappaB) activity. Western blotting was adopted to determine protein levels.
RESULTS: Two-hundred micromolar ginsenoside Rg3 significantly inhibited SW480
cell migration (P < 0.05). EMSA showed that Rg3 suppressed the DNA binding
ability of NF-kappaB. Dual luciferase reporter assay showed that Rg3 decreased NF
kappaB-regulated gene transcription (P < 0.01). Western blots indicated that Rg3
down-regulated expression of the NF-kappaB-regulated matrix metalloproteinase 9,
cyclooxygenase-2 and C-Myc. An NF-kappaB inhibitor, pyrrolidine dithiocarbamate,
enhanced the inhibitory effect of Rg3 on SW480 cell migration. CONCLUSION:
Ginsenoside Rg3 has a strong antitumor migration capability by suppressing NF
kappaB activity and expression of NF-kappaB-regulated gene products. It could be
a good adjuvant for colon cancer patients during the course of chemotherapy.
PMID- 26427116
TI - Effect of Chaihushugan San on expression of the Raf/mitogen-activated protein
kinase/extracellular signal-regulated kinase pathway in the hippocampi of
perimenopausal rats induced by immobilization stress.
AB - OBJECTIVE: We wished to study the impact of Chaihushugan San (CSS) on the
behavior of perimenopausal rats with liver-Qi stagnation (LQS) and to investigate
the effect of CSS on signal transduction of the Raf/mitogen-activated protein
kinase (MEK)/ extracellular signal-regulated kinase (ERK) cascade in the
hippocampi of rats induced by immobilization. METHODS: Twenty 52-week-old female
rats were divided into two groups by the random number table method: model
control group (MCG) and CSS group (CSSG), with 10 rats in each group. Ten-week
old female rats were used as the normal control group (NCG). CSS effects were
assessed using rats exposed to immobilization stress by measuring body weight and
sucrose consumption, serum hormone levels, and observing performance in the open
field test (OFT). Molecular mechanisms were examined by measuring the effect of
CSS on expression of Raf1, MEK1/2 and ERK1/2 mRNA in hippocampi using
quantitative real-time polymerase chain reaction and by measuring levels of these
proteins and related phospho-proteins using Western blotting. RESULTS:
Perimenopausal rats with LQS had decreased locomotor activity; reduced sucrose
consumption; and increased serum levels of corticotropin releasing hormone (CRH)
and corticosterone (CORT). Activation of hippocampal Raf/MEK/ERK cascade was
suppressed significantly in the MCG, and activation was increased after 21 days
of CSS treatment. CONCLUSION: CSS has significant effects upon relief of the
symptoms of LQS in immobilization-induced rats. The mechanism underlying this
action might (at least in part) be mediated by reversal of disruption of the
Raf/MEK/ERK pathway.
PMID- 26427117
TI - Effect of Liuweidihuang pill and Jinkuishenqi pill on inhibition of spontaneous
breast carcinoma growth in mice.
AB - OBJECTIVE: To investigate the preventing and treating action of Liuweidihuang
pill (LP) and Jinkuishenqi pill (JP) on spontaneous breast carcinoma in mice.
METHODS: A model of spontaneous breast carcinoma was derived from 11.5-month-old
female Kunming breeding mice following the delivery of several litters. The mice
were randomly divided into five groups: model control group (C), Liuweidihuang
pill high-dose group (LH; 4.6 g . kg(-1) . d(-1)), Liuweidihuang pill low-dose
group (LL; 2.3 g . kg(-1) . d(-1)), Jinkuishenqi pill high-dose group (JH; 4.6 g
. kg(-1) . d(-1)) and Jinkuishenqi pill low-dose group (JL; 2.3 g . kg(-1) . d(
1)). Cancer tissue volume was measured by water immersion. Histopathology was
analyzed by hematoxylin and eosin staining. Vascular endothelial growth factor
(VEGF), extracellular signal-regulated kinase (ERK) and cyclin D1 protein
expression in cancer tissue was assayed by western blotting. RESULTS: Compared
with the control group, cancer tissue volume and weight were lower in the LP and
JP groups, and survival time was longer. The expression of VEGF, ERK and Cyclin
D1 were inhibited in the LP and JP groups (P < 0.05), and cell differentiation
was increased. Tumor weights and volumes and VEGF, ERK and Cyclin D1 expression
in LL or LH were significantly lower than in JL and JH (P < 0.01). CONCLUSION:
Both LP and JP could restrain cancer growth and promote cancer cell
differentiation; moreover, LP was more effective than JP The likely mechanism of
action was via inhibition of VEGF, ERK and cyclin D1.
PMID- 26427118
TI - Estrogenic effect of the extract of Renshen (Radix Ginseng) on reproductive
tissues in immature mice.
AB - OBJECTIVE: To evaluate the estrogenic efficacy of Renshen (Radix Ginseng) (GS) on
reproductive target tissues in immature mice. METHODS: One hundred and ten female
immature Kunming (KM) mice, 21-day-old, were randomly assigned to eleven groups,
10 for each; one served as control group treated with 0.154 mg/kg estradiol
valerate (EV, n = 10), the rest were treated respectively with GS
intragastrically at a daily dose of 0.5, 1.0, 1.5, 3.0, 6.0, 12.0, 18.0, 24.0 and
30.0 g/kg (n = 10 in per group) for 7 days. The estrous cycle, uterine weight,
hormone levels in circulation and histomorphology changes of uterus and vagina
were scrupulously examined. The estrogen receptor (ER) alpha and ERbeta
expressions in the uterus and vagina were detected by immunohistochemistry and
western blotting. RESULTS: Treatment with GS at the dose of 12.0, 18.0 and 24.0
g/kg resulted significant estrogenic activity in the mice, as indicated by
advanced and prolonged estrous stage and increased uterine weight (all P < 0.05).
GS treatment substantially promoted development of reproductive tisue by
thickening the uterine endometrium and increasing vaginal epithelial layers. In
addition, treatment with GS induced significant up-regulation of ERalpha and
ERbeta expressions in reproductive tissues, and ERalpha up-regulation was
stronger than that of ERbeta. GS could raise levels of circulating estrogen,
simultaneously decrease levels of luteinizing hormone and follicle-stimulating
hormone (all P < 0.001) compared with the control group. CONCLUSION: Our findings
suggest that GS had estrogenic effect on reproductive tissues in immature mice by
stimulating biosynthesis of estrogen in circulation and up-regulating ERs.
PMID- 26427119
TI - Effect of Inonotus Obliquus Polysaccharides on physical fatigue in mice.
AB - OBJECTIVE: To evaluate the potential beneficial effects of Inonotus
obliquuspolysaccharides (IOP) on the alleviation of physical fatigue in mice.
METHODS: Sixty-four male mice were randomly divided into four groups (n = 16 per
group). Mice were orally administered IOP for a period of 14 days at 0, 100, 200
and 300 mg/kg/d, and were assigned to the control, IOP-100, IOP-200, and IOP-300
groups, respectively by the random number table method. Mice in the control group
received an oral administration of sterile distilled water. A forced swimming
test was performed for 8 mice per group at one hour after the last treatment. The
other 8 mice in each group swam for 30 min. Blood, liver and muscle samples were
taken after resting for 30 min. Levels of blood urea nitrogen and lactate, as
well as glycogen contents of the liver and muscle were measured. Morphology of
liver was observed by light microscopy. RESULTS: IOP extended the swimming time
of mice, and increased the glycogen content of liver and muscle, but decreased
blood lactic acid and serum urea nitrogen levels, IOP had no toxic effects on
major organs such as the liver as assessed by histopathological examinations.
CONCLUSION: IOP might be a potential anti-fatigue pharmacological agent.
PMID- 26427120
TI - Survival rate: an indicator of the management of acquired immune deficiency
syndrome using Traditional Chinese Medicine.
AB - Complementary and alternative medicine, including Traditional Chinese Medicine
(TCM), has been used as therapy against acquired immune deficiency syndrome
(AIDS) for almost 30 years. Based on evaluation indicators for AIDS treatment
using TCM, we discuss why the survival rate (which has been used widely in
Western Medicine) should be adopted as a new important indicator of TCM treatment
for AIDS. We advise that further prospective or retrospective cohort studies
should be carried out to confirm this hypothesis.
PMID- 26427121
TI - Epidemiological data on acupuncture and physical and rehabilitation medicine in
the European Union.
AB - OBJETIVE: To know the prevalence of acupuncturists within physical and
rehabilitation medicine specialists in Europe and their characteristics, as well
as to analyze the pathologies treated and therapeutic techniques used. METHODS:
This is a cross-sectional descriptive study based on a structured and closed
questionnaire. The study was carried out from October 2011 to May 2014. RESULTS:
A total of 115 specialists from 19 countries completed the questionnaire. The
mean characteristics of the physical and rehabilitation medicine (PRM)
specialists who are also acupuncturists in Europe were: women (62.6 %); mean age
of 47.91 years old; 4.20 years of physical and rehabilitation medicine school and
2.00 years of acupuncture training; 15.03 years of mean time of clinical practice
as physical and rehabilitation medicine specialists and 10.42 years of experience
as acupuncturists; 35.65 % had a doctorate (PhD) degree, obtained at a mean age
of 33.55 years old; working in a public hospital (80%); treating mainly
neurological conditions (48.1% ) and using mainly techniques such as
kinesiotherapy (11.81%), orthosis (10.40%) and electrotherapy (9.92%).
Acupuncture was applied by 32.2% of the participants mainly in musculoskeletal
conditions (27.38%). A mean number of more than 20 patients a day were treated by
47.04% of the specialists, being 41.8% of the patients (adults and children).
Significant differences were found between the variables, acupuncture and gender
(Pearson's correlation Index = 0.007). However, no differences were observed in
relation to acupuncture and age, doctorate degree, years of clinical practice and
workplace (all with P values > 0.05). CONCLUSION: In the European area, physical
and rehabilitation medicine specialists who are also acupuncturists are mainly
female, middle-aged, with 15 years of professional experience, PhD holders,
working in public hospitals, treating mainly neurological conditions with
kinesiotherapy and acupuncture, and treating over 20 patients a day (adults and
children) during a 7 h shift. Further epidemiological studies on PRM to provide
more information regarding the real situation of this medical specialty and the
possibility to open to Chinese traditional medicine techniques such as
acupuncture are necessary.
PMID- 26427122
TI - [A change in strides may change your life? A new exercise prescription to prevent
life-style-related diseases and avoidance of dependence on nursing care].
PMID- 26427123
TI - [From the background to the forefront: The sensor channel related to life and
death of cells and constancy of the living systems (3)].
PMID- 26427124
TI - HOW I FELL IN LOVE WITH JAPAN.
PMID- 26427125
TI - [Videofluoroscopic Examination of Swallowing Using the AsR Score for
Postoperative Swallowing Function in Oral Cancer Patients].
AB - To evaluate the postoperative swallowing function in head and neck cancer
patients, videofluoroscopic examination of swallowing (VF) proved useful as a
qualitative evaluation, but was complex as a quantitative evaluation. We made use
of the AsR score which consisted of a 10-point scale as a quantitative evaluation
of VF. To identify the usefulness of the AsR score, 146 patients who had
undergone extensive resection and reconstruction with free flaps or pedicle
grafts were reviewed. The AsR score of VF for the first time after surgery was
defined as "first score", and at the last time in the hospital was defined as
"last score". The correlations between the first score and continuity of direct
therapy, and between the last score and way of nutrition at the time of discharge
were examined. Using the ROC (receiver operator characteristic) analysis and the
AUC (area under the curve) the cut-off values of the AsR score were estimated.
One hundred and thirty one patients could continue direct therapy after the first
time of VF. The first score detected continuity of direct therapy with high
accuracy (AUC = 0.946), furthermore using a cut-off of 5, the sensitivity,
specificity, positive predictive value (PPV) and negative predictive value (NPV)
were about 96.2%, 86.6%, 98.4%, and 72.2%, respectively. At the time of
discharge, 138 patients had no limitation of oral intake and 8 patients had a
limitation e.g. PEG (n = 7) and a total laryngectomy for preventing aspiration (n
= 1). The last score detected oral intake ability with no limitation with high
accuracy (AUC = 0.925). Using a cut-off of 6, the sensitivity, specificity, PPV
and NPV were about 82.6%, 87.5%, 99.1% and 22.6%, respectively. The AsR score is
useful as a quantitative evaluation of postoperative swallowing function in oral
cancer patients.
PMID- 26427126
TI - [A Retrospective Series of 77 Pediatric Patients with Vertigo at a National
Center for Child Health and Development].
AB - The evaluation and management of vertigo in children varies among institutional
and medical specialties. The aim of this study was to describe the
characteristics of vertigo in children presenting at a national pediatric center.
Patients < 16 years old presenting with vertigo to the department of
otolaryngology at a national center for child health and development from April
2004 to October 2009 were included (N = 77; 42 males and 35 females; average age,
8.7 +/- 3.4 years) in this study. The most common diagnoses were vestibular
migraine (VM; N = 21), benign paroxysmal vertigo (BPV; N =16), unilateral
vestibulopathy (N = 12), and psychogenic vertigo (N = 8). Significant differences
were observed in the frequency of the diagnoses between children aged older and
younger than 7 years: BPV was most common in children < 7 years of age (p < 0.01)
and VM was most common in >= 27 years of age (p < 0.05). Because obtaining
adequate information from children for making a correct diagnosis is sometimes
difficult, acquiring sufficient information from the parents is important. In
addition, getting the parents to record the nystagmus during a vertigo attack
with a digital camera or cellular phone can be useful because observing the
nystagmus recorded on the video is helpful for making a diagnosis. Furthermore,
the parents are participating in their child's care by attempting to record the
attack, strengthening the relationship between the parents and the child. The
incidence of psychogenic vertigo is low (less than 10%). Therefore, although
physicians have recently tended to define the disorder as psychogenic when no
objective abnormality is found in a patient, making a diagnosis of psychogenic
vertigo is not recommended. Because vertigo can sometimes make a child anxious,
delivering the correct diagnosis and treatment at the early stage is important
for preventing anxiety in affected children.
PMID- 26427127
TI - [Intratympanic Steroid Treatment for Severe Idiopathic Sudden Sensorineural
Hearing Loss].
AB - Systemic steroid therapy is the only standard drug therapy for severe idiopathic
sudden sensorineural hearing loss (ISSHL). We have treated severe ISSHL patients
with double combined therapy, intravenous steroids (IVS) and hyperbaric oxygen
(HBO). In this study, we retrospectively examined the effects of intratympanic
steroids (ITS) by adding it to the double combined therapy. The study subjects
were 172 patients with severe ISSHL. Eighty patients (38 men and 42 women) were
treated with the double combined IVS and HBO therapy between April, 2007 and
July, 2010 (A group: Historical control arm). Ninety-two patients (51 men and 41
women) were treated with triple therapy, combined therapy with IVS and HBO plus
ITS, between August, 2010 and October, 2013 (B group: Current protocol arm). Each
group was divided into two subgroups; one with a pure-tone average (PTA) between
60 and 89 dB (A1 and B1) and the other with a PTA >= 90 dB. A 1, A2, B1, and B2
sub-groups had 56 (29 men, 27 women), 24 (9 men, 15 women), 64 (36 men, 28
women), and 28 (15 men, 13 women) patients, respectively. All patients were
treated within 30 days from the onset. There was a statistically significant
difference in hearing improvement between the A2 and B2 groups, whereas no
significant difference was observed between the A1 and B1 groups. Furthermore, a
significant difference was observed in all frequencies but 2 kHz between at the
A2 group and B2 group, but not between the A1 and B1 groups. Multivariate
logistic analysis revealed that the treatment method (double vs.. triple combined
therapies) had the strongest impact on hearing improvement in the ISSHL patients
with a PTA >= 90 dB. These results indicated that the B2 group demonstrated
better hearing improvement than the A2 group and suggested that the addition of
the ITS could be effective for profound ISSHL patients with a PTA >= 90 dB.
PMID- 26427128
TI - [Solitary Fibrous Tumors of the Nasal and Paranasal Sinuses].
AB - Solitary fibrous tumors (SFT) are uncommon neoplasm that arises in most cases
from the pleura. SFT has been rarely observed in the head and neck, but SFT of
the paranasal sinuses is especially rare, with 39 previously reported cases to
date including those reported in this abstract. Herein we describe three cases of
SFT in the paranasal sinuses that were successfully treated endoscopically. Two
of the three cases involved patients with no previous history of SFT. The lesion
of one of the patients was pathologically diagnosed as SFT preoperatively, but
the other was diagnosed as an angiogenic tumor without any biopsies. The tumors
were completely resected after arterial embolization by a transnasal endoscopic
procedure. The third case involved a 43-year old man, who had undergone medial
maxillectomy through a lateral rhinotomy incision to resect SFT four years and
seven months before. The tumor relapsed intracranially and, therefore, a
craniotomy procedure followed by endoscopic skull base surgery was performed.
Radiation therapy was performed postoperatively because the recurrent tumor was
pathologically identified as malignant SFT, which had been classified benign at
the time of the first resection. All three patients are presently alive with no
evidence of disease.
PMID- 26427129
TI - [Submucosal Partial-turbinectomy (SPT) Preceding an Endoscopic Sinus Surgery
(ESS) Procedure].
AB - Preceding a endoscopic sinus surgery (ESS), we have proposed performing a
submucosal partial-turbinectomy (SPT) which removes a part of the inferior nasal
concha bone attached to maxillary sinus with an antrostomy. By this method, we
could not only make a large antrostomy but also obtain good maneuverability by
opening the middle nasal meatus in ESS. We performed SPT preceding ESS in 140
cases (261 sides) between January 2012 and June 2014. The stenosis rates of the
middle nasal meatus were 14.2% (37 sides from 261 sides) in one month, 7.4% (18
sides from 243 sides) in three months and 3.7% (6 sides from 163 sides) in 6
months after surgery. The closing rates of the antrostomy were 1.5% (4 sides from
261 sides) in one month, 2.9% (7 sides from 243 sides) in three months and 6.7%
(11 sides from 163 sides) in 6 months after surgery. We considered that the SPT
method would contribute to secure sufficient ventilation routes for wound healing
of sinusitis following surgery on the mucous membrane. In addition, the SPT
method has merit from the point of deceasing risks of atrophic rhinitis and empty
nose syndrome by preserving most of the inferior nasal concha.
PMID- 26427130
TI - Vaspin as a Risk Factor of Insulin Resistance in Obstructive Sleep Apnea-Hypopnea
Syndrome in an Animal Model.
AB - BACKGROUND: In this study, we aimed to establish a chronic intermittent hypoxia
model in rats and explore the possible role of vaspin in insulin sensitivity.
METHODS: Healthy male Wistar rats were randomly divided into two groups: normal
control group (NC) and chronic intermittent hypoxia group (CIH). The NC group was
raised under physiological conditions and the CIH group was kept in the
plexiglass chamber between 9 am and 5 pm undergoing intermittent hypoxic
challenge for 8 hours/day for 8 weeks. Arterial blood pressure of rats (tail
cannulation) was measured before and after the study. Fasting plasma glucose
(FPG), total cholesterol (TC), triglycerides (TG), fasting insulin (FINS),
vaspin, and leptin levels were measured. Vaspin mRNA expression in visceral
adipose tissues was measured with Real Time-PCR. The protein levels of vaspin,
Akt and phospho-Akt in visceral tissues were determined by Western-blot. RESULTS:
At baseline, all the measurements in the CIH and NC groups were comparable. By
the end of the experiment, the blood pressure of the CIH group was significantly
higher than the NC group. The levels of FPG, FINS, TG, TC, leptin, and vaspin in
the CIH group were significantly higher than in NC group. Plasma vaspin levels
were correlated with FINS, HOMA-IR, and TG levels. Vaspin expression in both mRNA
and protein levels in visceral adipose tissues of the CIH group were clearly
higher than the NC group. Phospho-Akt protein level was decreased in visceral
adipose tissues of the CIH group compared to the NC group. CONCLUSIONS: In the
chronic intermittent hypoxia rat model, the expression of vaspin in visceral
adipose tissues and plasma were increased, which were correlated with insulin
resistance.
PMID- 26427131
TI - Design of Analytical Run Length for Clinical Chemistry Analytes.
AB - BACKGROUND: The expected number of unacceptable patient results E (Nu) can be set
as a patient-based quality goal. Analytical run length can be designed to limit E
(Nu) < 1. METHODS: The new internal quality control (IQC) strategy and length of
analytical run for each analyte was applied to routine IQC paralleled with the
way before redesign. IQC charts were produced by QC test results to analyze and
compare the performance of out-of-control error detection. RESULTS: Optimal
analytical run lengths designed by the quality control computer software QCCS
2008 were 39 for albumin, 61 for cholesterol, 900 for triglycerides, 112 for
aspartate aminotransferase, 279 for lactate dehydrogenase, 267 for alcaline
phospatase, 363 for total bilirubin, 151 for ceatinine, 230 for uric acid, 46 for
phosphorus PHOS, 158 for carbon dioxide, and 580 for glucose. After being
redesigned, IQC strategies for ALB, CHOL, and PHOS detected more out-of-control
error than before and achieved more cost-effectiveness. CONCLUSIONS: Using E (Nu)
as a QC performance measure, frequency of QC testing can be objectively designed.
Additionally, new QC strategies can help find more problems of testing systems
and promote efficiency and cost savings.
PMID- 26427132
TI - Age will affect the Growth and Mineralization Ability of the Rat Osteoblast.
AB - BACKGROUND: Primary culture of rat osteoblast cells serves as a model in in vitro
research of bone metabolism. But most of studies about osteoblast use fetal or
newborn rats for cell isolation, including researches about the post-menopausal
osteoporosis. This will affect the authenticity and reliability of the results.
These differences have been a concern in recent years. So far, little research
has focused on adult female rat osteoblasts. METHODS: In this study, a systematic
study was done regarding the proliferation, differentiation, and mineralization
of adult female rat osteoblasts. RESULTS: The study showed that the age of the
host may affect the growth and the mineralization ability of osteoblast.
CONCLUSIONS: The result of the study suggests that in vitro studies related to
osteoblasts should select the right host and appropriate observation points
according to the cell growth characteristics in order to ensure the consistency
of the actual changes.
PMID- 26427133
TI - The Therapeutic Effects of Thymosin alpha1 Combined with Human Immunoglobulin
(Ig) and Bundles on Severe Sepsis: a Retrospective Study.
AB - BACKGROUND: To explore the role of human immunoglobulin (Ig) and thymosin alpha1
therapy for severe sepsis through comparison between bundles combined with human
immunoglobulin (Ig) and thymosin alpha1 therapy group (A group) and bundles group
(B group). METHODS: A total of 526 subjects with severe sepsis in the ICU were
divided into two groups: bundles combined with human immunoglobulin (Ig) and
thymosin alpha1 therapy (A group) and bundles (B group). The two groups were then
divided into two subgroups: one group had a history of underlying disease (A1
group and B1 group) and the other did not (A2 group and B2 group). Data on
demographics, underlying diseases, infection site, organ involvement, duration of
artificial ventilation, APACHE II and SOFA scores on day-1 and day-14 after ICU
admission, and duration of ICU stay, were recorded. The study lasted 28 days. A
total of 526 subjects with severe sepsis in the intensive care unit (ICU) of
Beijing Chaoyang Hospital (affiliated with Capital Medical University; Beijing,
China) from January 2008 to December 2011 were selected. Bundles combined with
human immunoglobulin (Ig) and thymosin alpha1 therapy was administrated to 221
patients. 305 patients were treated with bundles. RESULTS: Compared with the B
group, the number of days of artificial ventilation was decreased (p < 0.005) and
ICU stay shortened (p < 0.001) in the A group. After 14 days of treatment, APACHE
II and SOFA scores were decreased (both p < 0.001). Mortality in the A group was
decreased by 13.89% (p < 0.005). The survival period in the A group was longer
than that of the B group (p < 0.001). CONCLUSIONS: Bundles combined with human
immunoglobulin (Ig) and thymosin alpha1 therapy may reduce APACHE II and SOFA
scores, shorten the time of artificial ventilation and length of ICU stay, and
improve the prognosis of subjects with severe sepsis.
PMID- 26427134
TI - The Seroprevalence of Some Pathogen Specific IgM in Children with Acute
Respiratory Tract Infections in Guangzhou Region, 2011 - 2012.
AB - BACKGROUND: Acute respiratory tract infections (ARTIs) are the leading cause of
morbidity and death in children < 5 years worldwide. The aim of this study is to
analyze the seroprevalence of nine pathogen specific IgMs in children with ARTIs
with respect to gender, age, and seasonality in the Guangzhou region. METHODS:
Serum samples were collected from 20160 children with ARTIs admitted to the
Guangzhou Women and Children's Medical Center between 2011 and 2012. Serum
specific IgM antibodies to nine respiratory pathogens, Mycoplasma pneumonia (MP),
Legionella pneumophila (LP), Coxiella burnetii (C. burnetii), Chlamydophila
pneumonia (CP), adenovirus (ADV), respiratory syncytial virus (RSV), type A and
type B influenza virus (IVA and IVB), and parainfluenza virus (PIV), were
detected using immunofluorescence assay. RESULTS: The male-to-female ratio of all
patients was 1.9:1. The median age was 3 years and 8 months with a significant
difference in seropositivity to respiratory tract pathogens between children from
different age groups. Seropositivity was detected in 43.53% of the children with
the top three pathogens being MP (33.15%), RSV (10.27%), and ADV (6.63%),
followed by IVB (2.63%), LP (2.25%), IVA (1.59%), PIV (1.57%), CP (0.27%), and C.
burnetii (0.13%). The prevalence of single, double, and triple seropositivity was
70.20% (6160/8775), 25.22% (2213/8775), and 4.57% (401/8775), respectively. The
total IgM seropositivity for any kind of pathogen in the nine kinds of pathogens
peaked in winter (46.53%), while the nadir was observed in summer (41.97%).
CONCLUSIONS: The top three seroprevalence of nine kinds of pathogen specific IgM
was MP, followed by RSV and ADV. The epidemic pathogen specific IgM had a season
specific seropositivity distribution. Seroprevalence of the pathogen should be a
focus of attention.
PMID- 26427135
TI - Frequencies of Six (Five Novel) STR Markers Linked to TUSC3 (MRT7) or NSUN2
(MRT5) Genes Used for Homozygosity Mapping of Recessive Intellectual Disability.
AB - BACKGROUND: Non-syndromic autosomal recessive intellectual disability (NS-ARID)
is an extremely heterogeneous genetic disorder. Therefore, to investigate these
genes, more research is required. One approach to investigate the NS-ARID loci is
homozygosity mapping which requires appropriate STR markers within or flanking
the gene/s of interest. In this research, we aimed to find novel STRs for two
common NS-ARID genes (TUSC3 and NSUN2) and, in addition, to identify allele
frequencies of those STR markers. METHODS: The study group included 119 unrelated
healthy individuals. STR markers were investigated using the UCSC genome browser
web site and SERV software. Genotyping was determined by multiplex PCR. Data were
evaluated using Gene Mapper software. Allele frequencies and observed
heterozygosity rates were calculated using PowerStatV12. Deviation from Hardy
Weinberg equilibrium and expected heterozygosity were assessed using the DNAView
software. RESULTS: In total, 56 alleles were detected. According to our research,
D8TUSC3SU8.3 and D5NSUN2SU0.5 were the most informative STR markers in MRT7 and
MRT5 loci, respectively and showed a high percentage of heterozygosity in Iranian
population. The observed range of allele frequencies was from 3.4% to 32.4% and
0.8% to 18.9% for MRT5 and MRT7 loci, respectively. Further, we have evaluated
other statistical surveys of these STR markers and discovered that all of the six
listed STRs were informative and five meet the Hardy-Weinberg equilibrium for the
tester group. CONCLUSIONS: Finding novel STRs, with high allele heterozygosity,
is one of the most significant current finding in the present study for the two
common NSARID genes. The recognized heterozygosity of these markers make MRT
flanking STR markers very efficient to be used in diagnostic medical genetics
labs or homozygosity mapping on NS-ARID.
PMID- 26427136
TI - Evaluate the Effect of Valproate Monotherapy on the Serum Homocysteine, Folate
and Vitamin B12 Levels in Epileptic Children.
AB - BACKGROUND: The data regarding Valproate and its influence on serum folate and
homocysteine levels are conflicting. The aim of this study was to evaluate
whether differences exist in homocysteine, folate, and vitamin B12 levels in
children receiving Valproate. METHODS: A total of 55 newly diagnosed epileptic
children with ages ranging from 2 to 15 years were enrolled at the start of study
but after 3 months follow up, the total sample size finally was only 50 epileptic
children. 5 children dropped out of study due to poor follow up. 50 age and
gender matched healthy control subjects were also studied on enrollment at the
start of study. Serum homocysteine levels were analyzed by enzyme immunoassay
method using the kits provided by Axis-Shield Diagnostics Ltd (Dundee DD2 1XA,
United Kingdom). Serum folate and serum vitamin B12 were estimated by Competitive
Chemiluminescent Enzyme Immunoassay method. RESULTS: The serum homocysteine level
in epileptic children was found to be significantly increased after Valproate
monotherapy as compared to before therapy. Moreover, a highly significant
decrease was observed in the levels of serum folate in epileptic children after
Valproate monotherapy as compared to before therapy. But a non significant
difference was observed in serum vitamin B12 levels in epileptic children before
and after Valproate monotherapy. CONCLUSIONS: Thus, we conclude that there is a
significant increase in the levels of homocysteine and a significant decrease in
the concentration of serum folate while vitamin B12 decreases non-significantly
after Valproate monotherapy. The atherogenic effect of increased serum
homocysteine level is well established; the patients under Valproate monotherapy
should be monitored for possible atherogenic effects. Considering the above
observation and results of children undergoing Valproate monotherapy, these
children should be screened for levels of serum homocysteine, folate, and vitamin
B12 and treated when their levels are found to be disturbed.
PMID- 26427137
TI - Virulence Genes and Antibiotic Susceptibilities of Uropathogenic E. coli Strains.
AB - BACKGROUND: The aim of this study is to detect the presence of and possible
relation between virulence genes and antibiotic resistance in E. coli strains
isolated from patients with acute, uncomplicated urinary tract infections (UTI).
METHODS: 62 E. coli strains isolated from patients with acute, uncomplicated
urinary tract infections (50 strains isolated from acute uncomplicated cystitis
cases (AUC); 12 strains from acute uncomplicated pyelonephritis cases (AUP)) were
screened for virulence genes [pap (pyelonephritis-associated pili), sfa/foc (S
and F1C fimbriae), afa (afimbrial adhesins), hly (hemolysin), cnf1 (cytotoxic
necrotizing factor), aer (aerobactin), PAI (pathogenicity island marker), iroN
(catecholate siderophore receptor), ompT (outer membrane protein T), usp
(uropathogenic specific protein)] by PCR and for antimicrobial resistance by disk
diffusion method according to CLSI criteria. RESULTS: It was found that 56
strains (90.3%) carried at least one virulence gene. The most common virulence
genes were ompT (79%), aer (51.6%), PAI (51.6%) and usp (56.5%). 60% of the
strains were resistant to at least one antibiotic. The highest resistance rates
were against ampicillin (79%) and co-trimoxazole (41.9%). Fifty percent of the E.
coli strains (31 strains) were found to be multiple resistant. Eight (12.9%) out
of 62 strains were found to be ESBL positive. Statistically significant
relationships were found between the absence of usp and AMP - SXT resistance,
iroN and OFX - CIP resistance, PAI and SXT resistance, cnf1 and AMP resistance,
and a significant relationship was also found between the presence of the afa and
OFX resistance. CONCLUSIONS: No difference between E. coli strains isolated from
two different clinical presentations was found in terms of virulence genes and
antibiotic susceptibility.
PMID- 26427138
TI - Molecular Analysis of IGH and Incomplete IGH D-J Clonality Gene Rearrangements in
Hodgkin Lymphoma Malignancies.
AB - BACKGROUND: We evaluated molecular clonality in immunoglobulin heavy chain (IGH)
and incomplete IGH D-J genes for improvement of clinical diagnosis of Hodgkin's
lymphoma (HL). We applied BIOMED-2 protocols in HL cases, which were previously
approved by clonality detection in non-Hodgkin lymphoma (NHL) cases. METHODS: We
investigated 50 consecutive FFPE samples of classical HL (cHL) patients to assess
IGH and IGH D-J clonal gene rearrangements by multiplex PCR protocols, which were
provided by the European Biomedicine and Health (BIOMED-2) Concerted Action
Project BMH4-CT98-3936. RESULTS: In the present study, there was a monoclonality
of 86% (43/50) including a clonality of 74% (37/50) for IGH and a clonality of
42% (21/50) in IGHD-J. In addition, a lack of clonality was detected in 14%
(7/50) of cases. Frequent gene rearrangements were detected in framework (FR) III
(54%) and FRII (20%), whereas no clonality was seen in FRI. Furthermore, a
monoclonality of 28% and 14% was detected in the DH(1-6)-JH and DH(see symbol)-JH
gene rearrangements, respectively. CONCLUSIONS: The present study suggests that
the complete IGH and incomplete IGH D-J clonality gene rearrangement assays using
BIOMED-2 protocols could be considered a valuable method for detection of clonal
gene rearrangements, especially in HL cases.
PMID- 26427139
TI - Differentiation between Transudate and Exudate in Pericardial Effusion has almost
no Diagnostic Value in Contemporary Medicine.
AB - BACKGROUND: The biochemical analysis of pericardial fluid for differentiating
transudate from exudate is often ordered and interpreted according to the
criteria extrapolated from pleural effusions. However, the validity of this
discrimination when applied to pericardial effusion is under question. METHODS:
Patients who underwent pericardiocentesis between January 2004 and February 2014
were identified. Among them, 216 had essential medical records available and
constituted the study population. The parameters specifically analyzed were the
following: lactate dehydrogenase, total protein and glucose concentrations in
both pericardial fluid and serum; pericardial fluid/serum ratios of lactate
dehydrogenase and total protein content; and pH and specific gravity of
pericardial fluid. RESULTS: Eighty-one percent of pericardial effusions were
classified as exudate according to Light's criteria. Both exudate and transudate
fluid characteristics were possible for all etiological causes except for
tuberculosis in which all were exudates. Although multiple cutoff points for all
parameters were tested, significant overlap between different causes persisted
(all having an area under the receiver operating characteristic curve of < 0.7).
Thus, a reasonable accuracy to differentiate one cause from another could not be
achieved. CONCLUSIONS: Although often ordered, the biochemical analysis of
pericardial fluid has almost no diagnostic value to distinguish among causes of
pericardial effusion in contemporary medicine.
PMID- 26427140
TI - Synovial Fluid alpha-MSH Levels are Inversely Correlated with Articular Cartilage
Degeneration in Anterior Cruciate Ligament Deficient Knees.
AB - BACKGROUND: Secondary osteoarthritis after ligament or meniscus injury generally
causes great burdens to patients. Alpha-melanocyte-stimulating hormone (alpha-MSH
), a 13 amino acid neuropeptide produced by intracellular cleavage of the
proopiomelanocortin (POMC) hormone, has been proven to suppress inflammation and
protect cartilage from damage. The present study was carried out to explore the
relationship between synovial fluid alpha-MSH levels and articular cartilage
degeneration in patients with anterior cruciate ligament (ACL) deficiency.
METHODS: 51 patients with ACL deficiency admitted to our hospital were enrolled.
The Noyes score method was used to assess articular cartilage damage
arthroscopically. Synovial fluid alpha-MSH levels were examined using a double
antibody radioimmunoassay method. Inflammation markers such as IL-6, MMP-3, and
degradation biomarker of collagen type II (CTX-II) were also explored by enzyme
linked immunosorbent assay (ELISA). RESULTS: The articular cartilage in ACL
deficiency patients deteriorated significantly with time after injury (r = 0.673,
p < 0.001). Synovial fluid alpha-MSH levels are inversely associated with Noyes
scores (r = -0.682, p < 0.001), levels of inflammation markers IL-6 (r = -0.302,
p = 0.035), MMP-3 (r = -0.652, p < 0.001) and degradation biomarker CTX-II (r =
0.584, p < 0.001). CONCLUSIONS: Synovial fluid alpha-MSH levels showed an
independent and negative correlation with articular cartilage degeneration in
patients with knee ACL deficiency. Supplementing with a-MSH may serve as a
possible adjuvant therapy for delaying cartilage degeneration after ACL injury.
PMID- 26427141
TI - Standardization of a Protocol for Obtaining Platelet Rich Plasma from blood
Donors; a Tool for Tissue Regeneration Procedures.
AB - BACKGROUND: To develop a protocol for obtaining autologous platelet rich plasma
in healthy individuals and to determine the concentration of five major growth
factors before platelet activation. This protocol could be integrated into the
guidelines of good clinical practice and research in regenerative medicine.
METHODS: Platelet rich plasma was isolated by centrifugation from 38 healthy men
and 42 women ranging from 18 to 59 years old. The platelet count and
quantification of growth factors were analyzed in eighty samples, stratified for
age and gender of the donor. Analyses were performed using parametric the t-test
or Pearson's analysis for non-parametric distribution. P < 0.05 was considered
statistically significant. RESULTS: Our centrifugation protocol allowed us to
concentrate basal platelet counts from 1.6 to 4.9 times (mean = 2.8). There was
no correlation between platelet concentration and the level of the following
growth factors: VEGF-D (r = 0.009, p = 0.4105), VEGF-A (r = 0.0068, p = 0.953),
PDGF subunit AA (p = 0.3618; r = 0.1047), PDGF-BB (p = 0.5936; r = 0.6095). In
the same way, there was no correlation between donor gender and growth factor
concentrations. Only TGF-beta concentration was correlated to platelet
concentration (r = 0.3163, p = 0.0175). CONCLUSIONS: The procedure used allowed
us to make preparations rich in platelets, low in leukocytes and red blood cells,
and sterile. Our results showed biological variations in content of growth
factors in PRP. The factors influencing these results should be further studied.
PMID- 26427142
TI - The Amount of Phosphorus in the Blood of Heroin Abusers Compared to that of
Healthy Subjects.
AB - BACKGROUND: The aim of the current retrospective study was to assess any
difference in terms of serum phosphate (P) between heroin addicts and healthy
subjects. METHODS: Between 2011 and 2012, under the authority of the Greek
Organization Against Drugs (OKANA), 30 regular heroin addicts, 22 males and 8
females (Group A) participated at the study. Between 2010 and 2011, 30 healthy
individuals, 22 males and 8 females (Group B), presented on an outpatient basis
for either fatigue or common flu symptoms without fever at the 424 Military
Hospital of Thessaloniki. RESULTS: No significant difference between group A and
B, in terms of either age (p = 0.454, Mann-Whitney test) or male/female ratio (p
= 0.573, Chi2 test), suggesting a homogeneity for the population of individuals
participating in the study. The mean values of serum-P in group A and B were 3.47
+/- 0.65 and 3.35 +/- 0.58, respectively (p = 0.45, Mann Whitney test).
CONCLUSIONS: The absence of statistical difference of serum-P between heroin
addicts and healthy subjects as shown in our results should be confirmed in
further studies.
PMID- 26427143
TI - Circulating Double-Stranded DNA in Plasma of Hemodialysis Patients and its
Association with Iron Stores.
AB - BACKGROUND: Chronic kidney disease (CKD) is characterized by oxidative stress,
and most of the adverse effects of CKD are mediated by iron-catalyzed ROS
generation. The DNA, in particular, is more susceptible to attack by ROS than
other proteins and membrane lipids. Considering the evidence on the relationship
between CKD, iron metabolism, and DNA damage, the purpose of this study was to
evaluate cell-free DNA in the plasma of HD patients and its association with iron
status biomarkers and kidney function. METHODS: Measurements of the circulating
cell-free DNA in plasma, iron, ferritin, transferrin and other biochemical
parameters were performed in 40 chronic hemodialysis (HD) patients and 40 healthy
controls. Blood samples were also collected 1 hour before and 1 hour after the HD
session to check whether a single HD session would be able to promote an increase
in cell-free DNA in the plasma. RESULTS: Cell-free DNA in plasma was
significantly increased in HD patients in comparison with healthy controls (p =
0.0017), and significant correlations were observed between cell-free DNA and GFR
and ferritin. Our findings showed that a single HD session was not able to
promote an increase in cell-free DNA. It was reported that increased ferritin
levels and reduced GFR were associated with higher circulating cell-free DNA.
CONCLUSIONS: The HD patients presented increased ceIl-free DNA. In addition, the
increase of ferritin levels and the decrease of GFR were associated with DNA
damage. We also observed that a single HD session was not able to promote an
increase in cell-free DNA.
PMID- 26427144
TI - Increased Synovial Fluid YKL-40 Levels are Linked with Symptomatic Severity in
Knee Osteoarthritis Patients.
AB - BACKGROUND: Elevated serum and synovial fluid (SF) YKL-40 levels have been
detected in knee osteoarthritis (OA) patients. The current study was focused on
the correlation between YKL-40 levels in serum or SF and symptomatic severity in
patients with knee osteoarthritis. METHODS: 144 patients with knee OA and 151
healthy individuals were recruited into this study. Symptomatic severity was
determined using Western Ontario and McMaster Universities Arthritis Index
(WOMAC) scores from OA patients. Serum and SF levels of YKL-40 were explored by
enzyme-linked immunosorbent assay. RESULTS: We found that YKL-40 levels in SF but
not serum were independently and positively related to WOMAC pain (r = 0.531, p =
0.001), physical disability (r = 0.380, p = 0.025), and total scores (r = 0.407,
p = 0.01) in knee OA patients. CONCLUSIONS: YKL-40 in SF could represent a
potential biomarker for assessing the symptomatic severity of OA.
PMID- 26427145
TI - Sirt1 and HMGB1 Regulate the AGE-Induced Pro-Inflammatory Cytokines in Human
Retinal Cells.
AB - BACKGROUND: Advanced glycation end products (AGEs) accumulate in the retinal
vascular cells, neurons, and glias of patients with diabetes mellitus and lead to
the pathogenesis of diabetic retinopathy (DR). METHODS: In the present study, to
elucidate the orchestrated interactions of high mobility group box 1 (HMGB1) and
silent mating type information regulation 2 homolog 1 (Sirt 1) in the AGE-induced
pro-inflammatory toxicity in retinal epithelial cells, we investigated the role
of HMGB1 and Sirt 1 in the AGE-induced pro-inflammatory cytokines and chemokines.
RESULTS: It was demonstrated that the expression of TNF-alpha, IL-1beta, IL-6,
MCP-1, RANTES and IP-10 was promoted by the AGE-BSA treatment dose-dependently.
The treatment with AGE-BSA also significantly promoted the HMGB1 at both mRNA and
protein levels, dose-dependently. And in addition, we confirmed that HMGB1
mediated the AGE-induced pro-inflammatory cytokines and chemokines in the AGE
treated ARPE-19 cells. Moreover, we found that the Sirt 1 was downregulated by
the AGE-BSA treatment at both mRNA and protein levels in the ARPE-19 cells, dose
dependently. Our further investigation recognized the regulatory role of Sirt 1
in the AGE-promoted pro-inflammatory cytokines and chemokines. The Sirt 1
inhibitor aggravated, whereas the Sirt 1 activator inhibited, the translocation
of HMGB1 and the promotion of AGE-induced IL-1beta and IL-6. CONCLUSIONS: Taken
together, we confirmed that AGE-BSA promoted HMGB1 but down regulated Sirt 1 in
human retinal cells. Sirt 1 was confirmed to regulate AGE-induced pro
inflammatory cytokines and chemokines via inhibiting the nuclear-to-cytoplasmic
translocation and release of HMGB1 in retinal ARPE-19 cells.
PMID- 26427146
TI - Ciculating miRNA-21 as a Biomarker Predicts Polycystic Ovary Syndrome (PCOS) in
Patients.
AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by
hyperandrogenism, hyperinsulinemia, and infertility. In PCOS, abnormal regulation
of relevant genes is required for follicular development. By binding to the 3'
untranslated region (3'URT), microRNAs (miRNAs) are widely involved in
posttranscriptional gene regulation. However, few studies have been conducted on
circulating miRNA expression in PCOS. This study aims to describe altered
expression of circulating miR-21 in PCOS. METHODS: The expression of serum miRNAs
of PCOS patients were explored using the TaqMan Low Density Array followed by
individual quantitative reverse transcription polymerase chain reaction assays.
The protein level of LATS1 was determined using Western blot. To validate whether
miR-21 targeted LATS1, the luciferase assay was applied. RESULTS: In comparison
with normal subjects, the circulating level of miRNA-21 was significantly
enhanced in PCOS patients. In PCOS patients, the expression levels of MST1/2,
LATS1/2, TAZ were much lower than the control subjects. Luciferase reporter assay
revealed that LATS1 was a downstream target of miR-21. CONCLUSIONS: In comparison
with normal subjects, serum miR-21 is obviously increased in PCOS patients.
Through targeting LATS1, miR-21 could prompt PCOS progression and could act as a
novel non-invasive biomarker for diagnosis of PCOS.
PMID- 26427147
TI - Analysis of the Molecular Evolution of the Mycobacterium Tuberculosis Drug
Resistant Gene rpoB in Asia Using a Bayesian Evolutionary Method.
AB - BACKGROUND: Tuberculosis (TB) is a serious communicable disease throughout the
world. Re-emergence of the TB epidemic is aggravated by the circulation of
multidrug-resistant Mycobacterium tuberculosis strains, and more than half of new
cases have occurred in Asia. Therefore, it is important to understand the gene
mutations underlying the development of rifampicin resistance in Asia. METHODS:
In this study, we classified the rifampicin-resistant Mycobacterium tuberculosis
(MTB) rpoB data downloaded from Genbank, based on 12 mutation points. The
relationship between the mutation sites and regional information was analyzed,
after which the mutation dates and mutation trends of the rpoB gene were
predicted by the Markov Chain Monte Carlo (MCMC) method. RESULTS: We discovered
that the mutation sites of the rpoB gene were disparate in different regions of
Asia. The results of this study clearly showed that drug-resistant gene mutations
in Asia started to increase in 2000 and peaked in 2006, indicating the
relationship between drug resistance and outbreak trends of TB. CONCLUSIONS: From
our analysis, it was not difficult to see the relationship between the mutation
rates of the rpoB gene and the outbreak of TB. Hence, to some degree, outbreak
trends of TB can be predicted through genotyping based on the rpoB gene.
PMID- 26427148
TI - Polymorphism of the Fcgamma Receptor II as a Possible Predisposing Factor for
Heparin-Induced Thrombocytopenia.
AB - BACKGROUND: Heparin-induced thrombocytopenia (HIT) represents a serious
complication of heparin treatment. IgG antibodies binding platelet factor 4 (PF4)
and heparin trigger the clinical manifestations of HIT. However, only a portion
of the antibodies have the ability to activate platelets, and these can be
identified by a platelet aggregation test (functional testing). However, this
expression has been detected to have a molecular cause, which is a mutation of
FcgammaRIIa. The FcgammaRIIa receptor is responsible for the activation of
platelets by antibodies in HIT. METHODS: To determine HIT, impedance aggregometry
using the Multiplate analyzer (MEA) as heparin-induced aggregation technique and
the Technozym HIT IgG ELISA test were used. The MEA method uses sensitization of
donor platelets with patient plasma in the presence of heparin at a concentration
of 0.5 IU/mL. The results were compared with the ELISA test. Mutation of
FcgammaRHa was assessed using the asymmetric real-time PCR method that is based
on the reaction with two hybridization probes and melting curve analysis.
RESULTS: Examined were 100 patients at a clinically intermediate and higher risk
of HIT according to the 4T's score. All samples were examined by the ELISA test
and MEA, with positive samples being further confirmed by high-concentration
heparin. In the group of patients, 10.0% were positive by MEA as compared with 4%
determined by ELISA. The results of genetic analysis of FcgammaRIIa did not
provide statistically significant differences between positive patients found by
the functional test as well as the ELISA test and seronegative patients.
CONCLUSIONS: The genetic mutation FcgammaRIIa is a predisposing factor for
manifestation of HIT in the form of thrombocytopenia, but the process of
seroconversion apparently needs another inducing factor. Therefore, the
examination of mutations can be classified as predisposing factors rather than to
confirm the diagnosis of HIT.
PMID- 26427149
TI - Association between Common Genetic Variants of alpha2A-, alpha2B-, and alpha2C
Adrenergic Receptors and Orthostatic Hypotension.
AB - BACKGROUND: The genetic background associated with the dysregulation of
orthostatic blood pressure remains poorly understood. The sympathetic nervous
system plays a pivotal role in the regulation of blood pressure, as well as in
response to positional changes. The essential role of adrenergic receptors in the
sympathetic nervous system prompted us to hypothesize that common genetic
variants of the alpha2-adrenergic receptor might contribute to the dysregulation
of orthostatic blood pressure in general populations. This study is to explore
the association between the polymorphisms of the alpha2-adrenergic receptor genes
and the occurrence of orthostatic hypotension in Chinese populations. METHODS:
The polymorphisms ADRA2A C-1291G (rs1800544), ADRA2B 301-303 I/D (rs28365031),
and ADRA2C 322-325 I/D (rs61767072) were genotyped in 317 patients with
orthostatic hypotension and 664 age- and gender-matched controls. Logistic
regression analyses, adjusted for multiple comparisons, were used to determine
the association between the allele/genotype of each ADRA2 gene and the risk of
orthostatic hypotension. RESULTS: No significant association was found between
the ADRA2A C-1291G, ADRA2B 301-303 I/D, and ADRA2C 322-325 I/D polymorphisms and
orthostatic hypotension. CONCLUSIONS: We concluded that the common polymorphisms
in the alpha2-adrenergic receptor gene is not associated with orthostatic
hypotension risk in Chinese.
PMID- 26427150
TI - Inhibition of Autophagy Increases Proliferation Inhibition and Apoptosis Induced
by the PI3K/mTOR Inhibitor NVP-BEZ235 in Breast Cancer Cells.
AB - BACKGROUND: The phosphoinositide 3 kinase (PI3K)/AKT/mammalian target of the
rapamycin (mTOR) pathway is a complicated intracellular pathway which leads to
cell growth and tumor proliferation and plays a significant role in breast
cancer. Multiple compounds targeting this pathway are being evaluated in clinical
trials. NVP-BEZ235, a novel and orally available dual PI3K/mTOR inhibitor, showed
great antitumor effect and provided a therapy strategy in breast cancer. METHODS:
In this study, we detect the effect of NVP-BEZ235 on cell viability, apoptosis,
and autophagy in a breast cancer cell line. We also test the effect of NVP-BEZ235
on the expression of PI3K/AKT/mTOR pathway proteins p-AKT, p-mTOR, and p-70S6K.
RESULTS: The results showed that the PI3K/AKT/mTOR proteins p-AKT, p-mTOR, and p
70S6K were obviously suppressed by NVP-BEZ235. NVP-BEZ235 inhibited cell
proliferation and induced apoptosis and autophagy in breast cancer cells. In
combination with autophagy inhibitors or autophagy gene knockdown, enhanced
growth inhibition and apoptosis was induced by NVP-BEZ235 in MCF-7 cells.
CONCLUSIONS: This study provides a novel treatment strategy that PI3K/AKT/mTOR
pathway inhibitors in combination with autophagy inhibitors lead to further
apoptosis in breast cancer cells.
PMID- 26427151
TI - Impact of Systemic Normobaric Short-Term Hypoxia on Pro-Inflammatory and Anti
Inflammatory Cytokines in Healthy Volunteers.
AB - BACKGROUND: Hypoxia has been shown to induce a microvascular inflammation, affect
the cell count of different types of immune cells, and influence cytokine
production in blood. In the present study, serum levels of different cytokines
were investigated to achieve insights into the effect of hypoxia on the balance
of inflammation and anti-inflammation. METHODS: Pro- (IL-8) and anti-inflammatory
(IL-10) cytokines were measured in an experiment exposing 12 healthy subjects (35
+/- 9 yr, 176 +/- 7 cm, 73 +/- 16 kg, BMI 23 +/- 4 kg/m2) to systemic, normobaric
hypoxia in a hypoxic chamber. In this chamber oxygen was replaced by nitrogen to
reach an oxygen content of 9.9% that is equivalent to an altitude of 5500 m
during 7 hours. Serum cytokine concentrations were analyzed using ELISA. RESULTS:
As expected, a significant decrease in peripheral oxygen saturation accompanied
by a significant increase in breathing frequency and heart rate were observed in
the subjects during hypoxia compared to baseline (BL). Blood leukocytes increased
slightly, but significantly in the course of hypoxia. A statistically significant
increase was measured for IL-8 serum level during hypoxia compared to the
baseline measurements (BL 12.0 +/- 1.1 pg/mL, hypoxia 16.2 +/- 1.6 pg/mL, p =
0.006). For IL-10 a statistically significant decrease was measured upon hypoxia
compared to baseline (BL 11.6 [6.2 - 43.31 pg/mL, hypoxia 8.3 [4.4 - 26.6] pg/mL,
p = 0.016). Additionally, a significant inverse correlation was found comparing
the anti-inflammatory cytokine IL-10 with the pro-inflammatory cytokine IL-8 (r =
-0.69, p < 0.001). CONCLUSIONS: The results of this study demonstrate a hypoxia
induced increase in pro- and decrease in anti-inflammatory cytokines reflecting
an increased pro-inflammatory status during hypoxia.
PMID- 26427152
TI - Fibroblast Growth Factor-23 and Carotid Artery Intima Media Thickness in Chronic
Kidney Disease.
AB - BACKGROUND: The cause of early-accelerated atherosclerosis development observed
in Chronic Kidney Disease (CKD) is not fully understood. The determination of the
relationship between the levels of fibroblast growth factor 23 (FGF-23) and the
development of endothelial dysfunction, left ventricular hypertrophy, and
myocardial infarction lends support to the possibility that FGF-23 plays a role
in the development of atherosclerosis in CKD. Only a few studies, however, have
been conducted that analyze the relationship between FGF-23 levels in the
progression of CKD and the development of atherosclerosis, and these studies have
generally been limited to those patients receiving dialysis therapy due to end
stage renal disease (ESRD). METHODS: In the present study, carotid artery intima
media thicknesses (IMT) were measured ultrasonically as a marker of
atherosclerosis in 91 patients with CKD stage 3 - 4 (61 female and 30 male, age
between 19 - 65 years, glomerular filtration rate [GFR] 15 - 60 mL/min 1.73 m2,
CKD was not related to diabetes mellitus, and without cardiovascular-cerebral
disease) in contrast to 36 healthy volunteers (26 female and 10 male, age between
19 - 65 years, GFR > 90 mL/min 1.73 m2, and without any diagnoses of acute or
chronic disease), and a possible role of FGF-23 on atherosclerosis was analyzed.
RESULTS: Patients were similar to controls with respect to age, gender, smoking
status, body mass index, and plasma glucose and lipid profile. On the other hand,
IMT measurements (p < 0.00001) and FGF-23 levels (p = 0.00012) were significantly
higher in patients than controls. IMT was measured above the subclinical
atherosclerosis limit of 0.750 mm in 54% of the patients. Multivariate regression
analysis showed that patients' age, high sensitive c-reactive protein (hsCRP),
and FGF-23 levels were independent predictors of IMT (p < 0.00001, r = 0.559).
Independent of other variables, every 1 MUmol/L increase in FGF-23 levels
resulted in 0.444 mm increase of IMT measurements in patients with CKD.
CONCLUSIONS: Our findings suggest that monitoring serum FGF-23 may be useful as a
non-invasive indicator of subclinical atherosclerosis in patients with chronic
kidney disease.
PMID- 26427153
TI - Relationship between the Level of Circulating Endothelial Micro-Particles in the
Blood and Blood Lipid Content in Uyghur and Han Patients with Acute Coronary
Syndrome.
AB - BACKGROUND: The aim of this study was to analyze the relationships between the
endothelial cell micro-particles (EMPs) blood level and the blood lipid in Uygur
and Han patients with acute coronary syndrome (ACS) in order to provide a
theoretical basis for the pathogenesis study of ACS. METHODS: 100 ACS patients
(50 cases for each ethnic group) were selected as the patient group from January
2012 to August 2013 from the Cardiology Sector of the People's Hospital of the
Xinjiang Uygur Autonomous Region, and 100 healthy subjects (50 cases for each
ethnic group) were selected as the control group. Blood samples were collected.
Flow cytometry was used to detect the EMP levels. An automatic biochemical
analyzer was used to detect the levels of the blood lipids and the related
indicators. RESULTS: The EMP levels in the patient group of both ethnicities were
higher than those in the control group (p < 0.05), although no statistically
significant differences were found in the EMP levels between Uygur and Han in the
patient groups, nor in the control group (p > 0.05). Multiple linear regression
analysis showed significant correlations between the EMP levels and the blood
lipid related indexes (p < 0.05), with a degree of correlation of 86.70%. Path
analysis indicated that the EMP level was mainly affected by high density
lipoprotein cholesterol (HDL-C) (p < 0.05). CONCLUSIONS: The EMP level in the
blood of ACS patients is significantly higher than in the control group, and the
levels between HDL-C and EMPs are negatively correlated. The pathogenesis of ACS
could be associated with the increase of the EMP level in the blood, and HDL-C
might affect the level of circulating EMPs.
PMID- 26427154
TI - Serum Levels of NTx and TRACP5b in Giant Cell Tumor of Bone and its Clinical
Implications.
AB - BACKGROUND: To investigate the serum levels of N-terminal telopeptide of type I
collagen (NTx) and tartrate-resistant acid phosphatase 5b (TRACP5b) in giant cell
tumor of bone (GCT) patients and the clinical implications. METHODS: 56 GCT
patients (29 males and 27 females, 15 to 60 years old with a median age of 28.0
years old) with clinicopathological characteristics of GCT were enrolled in the
Department of Bone Cancer, the Affiliated Cancer Hospital of Xinjiang Medical
University from October 2008 to October 2014. The enzyme-linked immunosorbent
assay (ELISA) was used to detect the serum levels of NTx and TRACP5b in the
patients. RESULTS: Compared with 21 patients who had a GCT of < 5 cm, the serum
levels of NTx and TRACP5b in the 35 patients with a GCT of >= 5 cm were
significantly increased (p < 0.05). Compared with those GCT patients who had a
grade I tumor, the levels of NTx and TRACP5b in grade II patients were not
increased (p > 0.05), but the levels of NTx and TRACP5b were significantly
increased in grade III patients (p < 0.05). Moreover, compared with the patients
in histologic stage I, the levels of NTx and TRACP5b in stage II GCT patients
were not increased (p > 0.05), whereas the levels in grade III patients were
significantly increased (p < 0.05). In addition, the location of the tumor had a
significant effect on the serum levels of NTx and TRACP5b (p < 0.05).
CONCLUSIONS: Our study suggests that serum NTx and TRACP5b are sensitive and
simple biomarkers to indicate aberrant bone metabolism in GCT patients, and they
may have a clinical significance in GCT diagnosis. Combined examination for both
markers helps in the classification of clinicopathological stages of GCT patients
and in the prognosis of the disease.
PMID- 26427155
TI - High-Sensitivity Cardiac Troponin T in Patients with Acute Myocardial Infarction
in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
AB - BACKGROUND: In clinical work, patients with acute exacerbation of chronic
obstructive pulmonary disease (AECOPD) often have high-sensitivity cardiac
troponin T (hs-cTnT) levels that surpass the 99th percentile of the normal
reference population, a cutoff used to screen patients for acute myocardial
infarction (AMI). However, a large proportion of these patients prove not to have
AMI and are frequently misdiagnosed and overtreated. We analyzed whether the
cutoff value of hs-cTnT for diagnosing AMI in AECOPD patients should be adjusted.
METHODS: This was a prospective study of 873 consecutive patients with AECOPD who
presented at the emergency department of West China Hospital of Sichuan
University from January 2010 to December 2013. Conventional cardiac troponin
(cTnT) was measured in patients' blood samples taken at presentation, and values
were compared with their final diagnoses. RESULTS: Among patients with a final
diagnosis other than AMI, 64.64% had a plasma hs-cTnT concentration above the
99th percentile of a normal reference population (14 ng/L). The median level of
hs-cTnT in AECOPD patients without AMI was 16 ng/L. The area under the receiver
operating characteristic curve (AUC) of hs-cTnT for diagnosis of AMI was 0.92
(0.85 - 0.99, p < 0.001) with a cutoff value of 60.5 ng/L. CONCLUSIONS: The
baseline levels of hs-cTnT were relatively high in AECOPD patients, and the
optimal cutoff value of hs-cTnT for AMI diagnosis (60.5 ng/L) was also higher
than that for non-AECOPD patients.
PMID- 26427156
TI - Reference Interval and Status for Serum Folate and Serum Vitamin B12 in a
Norwegian Population.
AB - BACKGROUND: Deficiencies of folate and vitamin B12 lead to an elevated serum
concentration of homocysteine which has been associated with many diseases
including cardiovascular disease. Laboratory algorithms often include initial
testing of serum folate and vitamin B12. Reference intervals for these vitamins
can vary significantly among populations for which dietary intakes may be
different. The aim of this study was to establish reference intervals in a
Norwegian population and to assess the folate and vitamin B12 status related to
reference intervals. METHODS: Blood samples were taken from 144 healthy
volunteers aged 18 - 65 years. A questionnaire provided data of medication,
medical history, vitamin supplementation, alcohol consumption, and use of oral
contraceptives and others. Serum folate and vitamin B12 concentrations were
measured on the Abbott Architect i2000. Reference values were calculated using
the bootstrap method. Results of serum folate, vitamin B12, and homocysteine from
1190 individuals from regional primary health care centers were evaluated related
to reference values and the proportion of individuals with deficiency was
estimated. RESULTS: Mean serum concentrations of folate and vitamin B12 were 11.9
nmol/L and 328 pmol/L, respectively. Men were found to have statistically
significant higher vitamin B12 concentrations than women. 95%-reference intervals
were calculated to 5.2 - 29.2 nmol/L for folate and 133 - 595 pmol/L for vitamin
B12. 1.1% of the study population has serum vitamin B12-concentrations < 133
pmol/L and 3.4% has serum folate concentrations < 5.2 nmoI/L. CONCLUSIONS: The
serum reference intervals for folate and vitamin B12 for a healthy, not vitamin
supplemented adult population were determined from 144 subjects. The application
of these intervals will assist in the evaluation of folate and vitamin status.
PMID- 26427157
TI - MicroRNAs as Biomarkers for the Diagnostics of Bladder Cancer: a Meta-Analysis.
AB - BACKGROUND: Bladder cancer (BCa) is the fifth most common cancer with significant
morbidity and mortality. Recently, numerous studies demonstrated that microRNAs
(miRNAs) are emerging as diagnostic biomarkers for BCa. However, the findings in
these studies are inconsistent. To systematically assess the potential diagnostic
value of miRNAs for BCa, a meta-analysis was performed in this study. METHODS:
Relevant literature was researched in PubMed, Embase, Cochrane Library, Chinese
National Knowledge Infrastructure (CNKI), and WanFang databases up to September
1, 2014. The pooled sensitivity, specificity, positive likelihood ratio (PLR),
negative LR (NLR), diagnostic odds ratio (DOR), and area under the SROC curve
(AUC) value were analyzed by the random-effects model, whose parameters reflected
the overall diagnostic performance of miRNAs. RESULTS: Thirty studies from 10
individual publications, including 1019 BCa patients and 690 controls, were
included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR,
DOR, and AUC were 0.80 (95% CI: 0.78 - 0.81), 0.74 (95% CI: 0.72 - 0.76), 3.22
(95% CI: 2.68 - 3.87), 0.26 (95% CI: 0.21 - 0.32), 15.20 (95% CI: 10.25 - 22.53)
and 0.85, respectively, indicating a moderate diagnostic accuracy for BCa.
Moreover, our subgroup analyses showed that analysis of multiple miRNAs (AUC,
sensitivity, and specificity of 0.913, 0.86, and 0.80, respectively) yielded a
higher diagnostic accuracy than of single miRNAs (AUC, sensitivity, and
specificity of 0.84, 0.78, and 0.73, respectively) in BCa diagnosis. In addition,
as biomarkers, miRNAs are more suitable for the diagnosis of non-muscle-invasive
BCa (NMIBCa) with AUC of 0.84, sensitivity of 0.74, and specificity of 0.77 than
muscle-invasive BCa (MIBCa) with AUC of 0.79, sensitivity of 0.73, and
specificity of 0.73. CONCLUSIONS: The present meta-analysis suggests that miRNAs
are potential novel biomarkers for detection of BCa. However, further validation
studies are still needed to confirm our findings.
PMID- 26427158
TI - Comparison of the Microarray-Based Assay, the Real-Time PCR Assay, and the
Bidirectional Sequencing Method for CYP2C19 Genotyping.
AB - BACKGROUND: Cytochrome P450 2C19 (CYP2C19) is a clinically important enzyme that
metabolizes a wide variety of drugs. Recently, some new genetic assays designed
to identify the CYP2C19 genotype were introduced. METHODS: We compared the
abilities of the microarray-based Verigene CYP2C19 Test (Nanosphere, USA) and the
AccuPower Real-time PCR CYP (*2,*3,*17) assay (Bioneer, Korea) with the ability
of the bidirectional sequencing method for the detection of CYP2C19 genotypes in
78 whole blood samples. RESULTS: Among 78 specimens, 28 were *1/*1, 1 was *1/*17,
27 were *1/*2, 10 were *1/*3, 8 were *2/*2, 1 was *3/*3, and 3 were *2/*3. In the
initial test, five samples (6.4%) in the Verigene assay and two samples (2.4%) in
the AccuPower assay failed to generate definite results. All retests with both
assays generated definitive results. In both assays, the results of CYP2C19
genotyping showed 100% final concordance with those obtained by the direct
sequencing method. CONCLUSIONS: These two assays could be useful for the
identification of CYP2C19 genotypes in clinical laboratories.
PMID- 26427159
TI - [A Prussian in Venice: the botanist Melchior Wieland (1520-1589), pioneer in
botanical field research in the Levant].
AB - The Italian physician and botanist Prospero Alpini (1553-1617) is considered as
one of the most famous 16th Century Italian botanists having explored the plant
species of Egypt and the Near East. Alpinis best-known works as for example De
medicina Egyptiorum (Venetijs 1591) or De plantis Aegypti liber (Venetijs 1592),
however, wouldn't certainly have been made possible without the influence of his
academic teacher, the Prussian physician and botanist Melchior Wieland (ca. 1520
1589), having been applied director of the botanical garden of Padua in 1561.
This study is therefore dedicated to the life, academic career, works and
reception of this nearly forgotten botanist.
PMID- 26427160
TI - [The medical faculty of the Wittenberg University 1502-1817 - the stats of
research].
AB - This essay provides an overview of the scientific literature regarding the
history of the Faculty of Medicine at the University of Wittenberg, Germany. The
University of Wittenberg was the domain, where Martin Luther and Philipp
Melanchton worked; in the 16th century it was one of the greatest universities of
the Holy Roman Empire. There has been a controversial discussion on the history
of the Faculty of Medicine since the mid-19th century. Since the 1980s, it is an
accepted and studied field of research on its own. The various publications on
the topic can be subdivided into three specific areas: 1. Reformation and
medicine, 2. biographic works on professors of medicine, and 3. historical works
regarding social and librarian fields of research. The results of those works can
be interpreted and merged in view of the Faculty of Medicine. However, for a
revalidation of the faculty's role within an European scientific scene further
scrutiny of sources is needed.
PMID- 26427161
TI - The Historical Discourse on the Etiology of Anorexia Nervosa. Results of a
Literature Analysis.
PMID- 26427162
TI - Anatomical Modernity in Red Vienna: Textbook for Systematic Anatomy and the
Politics of Visual Milieus.
PMID- 26427163
TI - [From the history of Roger commentators].
AB - The biblical manuscript A 12, preserved in Duesseldorf's Federal and University
Library (Universitaets- und Landesbibliothek Duesseldorf), dates from the mid
13th century. In the course of its scholarly analysis, a piece of parchment was
found in the interior board, where a fragment of a surgical text is written on.
Judging from the writing, the original manuscript came from southern France
(Montpellier) and dates from the late 13th century. Several pas- sages quote
"M[agister] W[ilhelmus] de Congenis", but the text bears only a vague resem-
blance to Pagel's (1891) and Sudhoff s (1918) editions. Upon the other hand, the
author was guided by Roger Frugardi's 'Chirurgia', which presumably gave the
structure for Wilhelm's lectures. The edition of the fragmentary text presents a
yet unknown example of student notes referring to William of Congenis and
illustrates the complex history of Roger commentaries.
PMID- 26427164
TI - [An honorable lie: Abderhalden's letter for deletion of Jewish members of the
Leopoldina - anticipatory obedience or protective statement?].
AB - In 1938, the president of the German Academy of Scientists Leopoldina, Emil
Abderhalden, on his own accord confirmed to the NS-Gauleiter and minister that
"to the Academy belong only members who are not Jews" and that the Leopoldina's
membership had "already for some time" coincided with contemporary demands. When
analysed according to the relevant sources, these exculpatory statements turn out
to be intentionally false and, thereby, Abderhalden's only known proven lie,
albeit an honourable one since the National Socialist leadership then had no
reason to intervene in the Leopoldina's membership affairs. With this letter
Abderhalden attempted to suggest that the Leopoldina had always operated in
anticipatory obedience--which was not the case in reality.
PMID- 26427165
TI - How to Increase Concentration & Focus Using Intention Statements.
PMID- 26427166
TI - An Emerging Role for RN's: the RN Primary Care Coordinator.
PMID- 26427167
TI - Oklahoma Nurse Practitioners Need Full Practice Authority.
PMID- 26427168
TI - Creating a Culture of Innovation.
PMID- 26427170
TI - A PHYSICIANS ROLE IN DISMISSING STAFF.
PMID- 26427171
TI - FIGHTING BACK. PART 1. Overcome the challenges of independent practice.
PMID- 26427173
TI - Improving practice-payer collaboration.
PMID- 26427174
TI - PATIENT LANGUAGE BARRIERS: YOU ARE RESPONSIBLE.
PMID- 26427175
TI - CLARIFYING INCIDENT-TO BULLING.
PMID- 26427176
TI - SETTING UP PATIENT PAYMENT PLANS: WHEN TO USE A THIRD PARTY.
PMID- 26427177
TI - Cardiometabolic Syndrome.
PMID- 26427179
TI - Suzy.
PMID- 26427180
TI - Why physicians must develop a mobile technology strategy.
PMID- 26427182
TI - PROTECT YOUR DATA FROM HACKERS IN 5 STEPS.
PMID- 26427183
TI - Nuggets of Knowledge and Opportunity.
PMID- 26427184
TI - Decreasing Emergency Department Visits and Hospital Admission in the Pediatric
Tracheostomy Population.
AB - Providing a child with a tracheostomy is often a life saving intervention.
However, the impact on the family is frequently life changing. Parents of
children with tracheostomies require specialized training in order to provide
safe care for their child in the home setting. The purpose of this project was to
investigate the outcomes of a parent education program delivered by a nurse
practitioner and its impact on patient follow up for children with tracheostomies
living at home. This quasi-experimental evidenced based project was based on an
intervention group of five parent-child dyads and a control group of 23 parent
child dyads. It took place at a local children's hospital. This project compares
the number of emergency room visits, inpatient admissions, phone calls and ENT
clinic visits between the two groups. A significant increase in the number of
phone calls to the clinic was found in the intervention group (p = 0.018).
However, there was no significant change in the number of emergency room visits
or inpatient admissions in the intervention group. The small number of
participants in the intervention group limits the applicability of the results,
however clinical significance exists. This study demonstrated that a structured
parent education program with scheduled follow up with a nurse practitioner
provides a positive impact on the care of the pediatric tracheostomy patient.
PMID- 26427186
TI - Diagnostic Considerations of Ultrasound versus Computed Tomography for Pediatric
Inflammatory Neck Infections.
PMID- 26427185
TI - Children With Sensorineural Hearing Loss And Referral To Early Intervention.
AB - OBJECTIVE: Sensorineural hearing loss (SNHL) is identified at a rate of 1-3 per
1,000 newborns in the United States. Timely referral to Early Intervention (EI)
services is critical, as early EI referral has been shown to improve outcomes,
including speech and language development, social and emotional development, and
academic performance. The objective of this study was to determine the rate at
which children diagnosed with SNHL at a large tertiary referral center were
referred to EI, and, if so, by whom. In addition, we sought to determine the time
from the diagnosis of SNHL to the completion of the referral, and what services
were received. DESIGN: Prospective observational study METHODS: Data were
collected by telephone survey and review of the electronic medical record
RESULTS: Children with SNHL were referred to and participated in EI at a high
rate. All children in this study (100%) were referred to EI. Most (92%) of the
children were referred by 6 months of age, and almost all (98%) participated in
EI. CONCLUSION: At our institution, children with SNHL are being consistently
referred to EI, meeting the goals of the Early Hearing Detection and Intervention
program. Future outcomes research can now be designed to determine whether
achieving these benchmark goals improves children's academic performance,
expressive and receptive language skills, and development as compared to age
matched, normal hearing peers.
PMID- 26427187
TI - Case Presentation: Incidental Finding of a Rare Syndrome in 13-Year-Old Girl.
PMID- 26427188
TI - A Case Study of Medical and Surgical Management of a Cystic Fibrosis Patient.
PMID- 26427190
TI - Commemorating the Anzac nurses.
PMID- 26427191
TI - Praise for Christchurch Hospital infection control measures.
PMID- 26427192
TI - War memorial honours nurses.
PMID- 26427193
TI - Workplace behaviours.
PMID- 26427194
TI - HPV immunisation research.
PMID- 26427195
TI - The Kaiwhakahaere comments.
PMID- 26427196
TI - Celebrations honour caregivers' work.
PMID- 26427197
TI - Government to appeal respite carer decision.
PMID- 26427198
TI - DHB MECA deal next month.
PMID- 26427199
TI - Morale of nurses falling--research.
PMID- 26427200
TI - Mental health care 'inequitable'.
PMID- 26427201
TI - Nurse appointed to suicide prevention programme.
PMID- 26427202
TI - Nurse practitioner heads rural advocacy network.
PMID- 26427203
TI - ED waiting time target causing problems.
PMID- 26427204
TI - Flu vaccinations now underway.
PMID- 26427205
TI - Containing Ebola. Helping nurse and save many patients with the Ebola Virus is a
source of much pride for one returning New Zealand nurse.
PMID- 26427206
TI - Army nursing service goes to war.
PMID- 26427207
TI - Nursing 'our boys' during the Great War.
PMID- 26427209
TI - Marking 100 years of military nursing.
PMID- 26427208
TI - Making some sense of war.
PMID- 26427210
TI - Honouring the Marquette nurses.
PMID- 26427211
TI - Electricity in the brain.
PMID- 26427212
TI - Pioneering nurse-led clinics enhance patient care.
PMID- 26427214
TI - In praise of patient portals.
PMID- 26427213
TI - Supporting patients on a life-changing journey.
PMID- 26427215
TI - Preserving nursing history.
PMID- 26427216
TI - How can unions help achieve effective staffing?
PMID- 26427217
TI - Protecting patients with diminished competence.
PMID- 26427219
TI - DHB members to consider pay deal.
PMID- 26427218
TI - Professionally yours.
PMID- 26427220
TI - Responding to member issues.
PMID- 26427221
TI - Protecting vulnerable communities.
PMID- 26427222
TI - Diabetes: Developing nurse prescribing.
PMID- 26427223
TI - Smokefree: Nurse researchers gather in Auckland.
PMID- 26427224
TI - Case management's value is finally recognized. What happens now? .
AB - In recent years, case management has been recognized as a key in improving
healthcare quality and reducing costs, but while hospitals are giving case
managers more responsibilities, many administrators are not approving an increase
in staff to handle the extra work. Case managers can help their hospital succeed
with the Centers for Medicare & Medicaid Services' Value-based Purchasing
program, the readmission reduction program, and bundled payments. Case management
directors should make sure the hospital's senior leadership understands the roles
and responsibilities of case managers and how their interventions can affect
outcomes and the bottom line. The number of caseloads depends on the case
management model, the responsibilities of case managers, and whether they have
assistants or case management extenders who can take over some tasks and allow
the licensed staff to work at the top of their licenses. Don't let technology
replace communication and patient-centered interactions.
PMID- 26427225
TI - There's no magic number for case management caseloads.
PMID- 26427226
TI - Case managers just can't do it all alone.
PMID- 26427227
TI - Technology is essential today, but there are pitfalls.
PMID- 26427228
TI - CASE MANAGEMENT INSIDER. The Top 10 Mistakes You May Be Making In Your Case
Management Department! Part 4.
AB - We have now completed our review of the top 10 mistakes you may be making in your
case management department. I've included tips and strategies for correcting
these mistakes if you are facing them in your organization. If you follow these
suggestions, you will help to keep your case management practice and your
department on track and moving forward!
PMID- 26427229
TI - Care management assistants help improve patient flow, care transitions.
PMID- 26427230
TI - Community partnerships keep patients safe after discharge.
PMID- 26427231
TI - CMS continues its push for quality-based reimbursement.
PMID- 26427232
TI - [Hoarding].
AB - Hoarding is a mental disorder having its onset at young age and often worsening
with age, manifested as a need of storing up goods to an extent that
significantly hampers everyday life. In the light of conducted studies, at least
1 to 2% of the adult population suffers from hoarding. Upon increased compulsive
hoarding with aging, problems arise especially for those living alone. Hoarding
differs from obsessive-compulsive disorder in its course and treatment response.
Treatment of hoarding disorder is based on methods applied in cognitive behavior
therapy.
PMID- 26427233
TI - [Obesogenic food environment explains most of the obesity epidemic].
AB - The food environment has undergone a considerable chance over the past 30 to 40
years. Availability, variation and low costs increase the consumption of foods.
Other changes in the food environment include: increase of the high-energy
density foods, increased consumption of sugar-sweetened beverages, large portion
sizes, large packages, increased variety, increased visibility of foods, and
marketing food to children, all known to augment eating and energy intake.
Societies should especially protect children from the obesogenic environment by
legislation and other regulations. The main targets should be decreasing the
consumption of high-energy density foods and sugar-sweetened beverages and
returning the sizes of portions and packages to normal.
PMID- 26427234
TI - [Breast lump in a young woman].
AB - While a breast lump in a young woman is almost always benign, the lump may also
be caused by breast cancer and rare malignant tumors. Factors increasing the risk
of breast cancer, and especially the family history in respect of breast cancer
and ovarian cancer should be mapped out from the anamnesis. Clinical examination
of both breasts and lymph node regions is carried out in a systematic manner.
Benignity of the lump must in all cases be confirmed by imaging and when
necessary, by taking a core needle biopsy. Among the benign tumors of the breast,
only a small symptomless fibroadenoma confirmed by core needle biopsy does not
require an assessment by a surgeon.
PMID- 26427235
TI - [Managing aggression and violence associated with psychosis].
AB - Risk for violence in psychosis is associated with the subject's history of early
onset antisocial behavior, substance abuse, suicidal ideation, lack of insight,
and non-adherence to antipsychotic medication. These risk factors can be managed
by effective treatment for psychosis, with the exception of predatory antisocial
aggression. Generally, this group of patients is at considerable risk for
untreated conditions. There is, however, no pharmacological treatment indicated
solely for aggression. Physical violence can often be avoided by alertness and
risk monitoring, and by attentive customer service skills. Safety at work is our
shared responsibility.
PMID- 26427236
TI - [Tick-borne encephalitis in Finland from 2010 to 2012].
AB - The frequency of occurrence of tick-borne encephalitis has increased
significantly in Europe and Finland during the past twenty years. There has been
a suspicion that the Finnish cases have at least over the last few years been
more severe than described in the literature. We analyzed the approximately one
hundred cases of tick-borne encephalitis diagnosed in Finland over a three-year
period. In two thirds of the patients general physical condition deteriorated
clearly, the disease caused permanent disability or the patients required
supportive measures in the hospital, such as ventilator therapy. Assessment of
the course and severity of the disease would seem to be impossible on the basis
of individual symptoms, such as duration of fever.
PMID- 26427237
TI - [Respiratory insufficiency due to duplications of the oesophagus].
AB - Duplications of the oesophagus are uncommon congenital malformations with
possible occurrence in any part of the gastrointestinal tract. The duplications
may be cysts, diverticula or tubular-shaped. Cysts may even occur further away
from the gastrointestinal tract, not necessarily having contact with it. I
present a patient case, in which a 13-month-old child was brought to the
emergency room due to gradually increasing dyspnea. The child made a full
recovery after the surgical procedure.
PMID- 26427238
TI - "Jeremy Hunt's speech downplayed nurses".
PMID- 26427239
TI - Time to be called on unsocial rates.
PMID- 26427241
TI - Midwives to be regulated by new system.
PMID- 26427240
TI - Health secretary outlines latest move on safe staffing guidance.
PMID- 26427242
TI - Race equality rules leave trusts facing 'uncomfortable' truth.
PMID- 26427243
TI - New radio series explores state of nurse education.
PMID- 26427245
TI - Colchester trust introduces new nursing badge.
PMID- 26427244
TI - Rotherham safeguarding review says school nurses overstretched.
PMID- 26427246
TI - 'Grave concerns' for hard-won health visitor gains.
PMID- 26427247
TI - Nurse-led primary care models could be answer to GP shortage.
PMID- 26427248
TI - Nursing team pioneers care home link role.
PMID- 26427249
TI - "All staff must know when and how to refer to palliative care".
PMID- 26427250
TI - "We need to plan creatively to solve growing healthcare needs".
PMID- 26427251
TI - In praise of gerontology.
PMID- 26427252
TI - "Nurses must be familiar with acute kidney injury guidelines".
PMID- 26427253
TI - Acute kidney injury: prevention and recognition.
AB - Acute kidney injury (AKI) is common and often preventable. Nurses should be able
to recognise it and respond when it occurs. Through prevention or early
detection, nurses can help to reduce morbidity and mortality associated with AKI,
improving patients' quality of life and reducing the financial impact of AKI on
the NHS.
PMID- 26427254
TI - How we are changing mental health nursing.
PMID- 26427255
TI - A nurse-led pathway to treat self-harm injuries.
AB - Self-harm occurs frequently in psychiatric hospitals and other mental health and
outpatient settings. Many patients at the Ayr Clinic are at risk of self-harm and
often access the local accident and emergency service for minor injury care. The
medical and nursing response to people who repeatedly self-harm, given increasing
pressures and dwindling A&E resources, can often be one of impatience,
frustration and hostility. A nurse-led pathway was developed by the Ayr Clinic
and NHS Ayrshire and Arran to fast-track the assessment and treatment of such
injuries and improve health professionals' attitudes towards these patients. This
project was winner of the Nursing Times emergency and critical care awrad 2014.
PMID- 26427256
TI - Systemic corticosteroids for acute COPD exacerbations.
PMID- 26427257
TI - Improving outcomes with online COPD self-care.
AB - If self-management was implemented properly, the NHS could save an estimated
L235m over the next 10 years. An online self-management system for people with
chronic obstructive pulmonary disease allows patients to access information
whenever they need it. A comparison of conventional and online approaches to COPD
self-management showed the online system is more effective in terms of health
status and inhaler technique.
PMID- 26427258
TI - Caring for patients with lower limb amputation.
AB - In 2014 a National Confidential Enquiry into Patient Outcome and Death report
examined the care of people requiring lower limb amputation as a consequence of
complications associated with vascular disease or diabetes. It suggests that less
than half of patients who undergo surgery receive good care. This article
summarises the key findings of the report and the implications for nursing
practice.
PMID- 26427259
TI - 60 seconds with Liz McCall.
PMID- 26427260
TI - Good care is in the blood.
PMID- 26427261
TI - Imagining the New NEHA.
PMID- 26427262
TI - How Clean Are Hotel Rooms? Part I: Visual Observations vs. Microbiological
Contamination.
AB - Current evidence of hotel room cleanliness is based on observation rather than
empirically based microbial assessment. The purpose of the study described here
was to determine if observation provides an accurate indicator of cleanliness.
Results demonstrated that visual assessment did not accurately predict microbial
contamination. Although testing standards have not yet been established for hotel
rooms and will be evaluated in Part II of the authors' study, potential microbial
hazards included the sponge and mop (housekeeping cart), toilet, bathroom floor,
bathroom sink, and light switch. Hotel managers should increase cleaning in key
areas to reduce guest exposure to harmful bacteria.
PMID- 26427263
TI - How Clean Are Hotel Rooms? Part II: Examining the Concept of Cleanliness
Standards.
AB - Hotel room cleanliness is based on observation and not on microbial assessment
even though recent reports suggest that infections may be acquired while staying
in hotel rooms. Exploratory research in the first part of the authors' study was
conducted to determine if contamination of hotel rooms occurs and whether visual
assessments are accurate indicators of hotel room cleanliness. Data suggested the
presence of microbial contamination that was not reflective of visual
assessments. Unfortunately, no standards exist for interpreting microbiological
data and other indicators of cleanliness in hotel rooms. The purpose of the
second half of the authors' study was to examine cleanliness standards in other
industries to see if they might suggest standards in hotels. Results of the
authors' study indicate that standards from other related industries do not
provide analogous criteria, but do provide suggestions for further research.
PMID- 26427264
TI - Prevalence, Knowledge, and Concern About Bed Bugs.
AB - Recent research suggests that the resurgence of bed bugs in the U.S. has occurred
at an alarming rate. Assumptions have been made that socioeconomic status is not
associated with the prevalence of bed bug infestations. Little information is
available at the local level, however, about the prevalence of bed bugs in
private homes. The authors' pilot study aimed to identify prevalence, knowledge,
and concern about bed bugs in one higher income village in Ohio utilizing survey
methodology. Responses from 96 individuals who completed the Prevalence,
Knowledge, and Concern About Bed Bugs survey were utilized for analysis. The
majority of the sample respondents were white and 95% reported that they owned
their residence. Only 6% knew someone with bed bugs. Additionally, 52% reported
they were somewhat concerned about bed bugs. About 46% reported that they had
changed their behavior. For a higher income area, the prevalence was dissimilar
to the rate reported in the general public (about 20%). This suggests that bed
bugs may be an environmental issue effecting low-income populations
disproportionately. Further research is needed in areas of differing
socioeconomic levels.
PMID- 26427265
TI - Implications of the Fukushima Nuclear Disaster: Man-Made Hazards, Vulnerability
Factors, and Risk to Environmental Health.
AB - The objective of this article was to examine the environmental health
implications of the 2011 Fukushima nuclear disaster from an all-hazards
perspective. The authors performed a literature review that included Japanese and
international nuclear guidance and policy, scientific papers, and reports on the
Chernobyl and Three Mile Island disasters while also considering all-hazards
preparedness rubrics in the U.S. The examination of the literature resulted in
the following: a) the authors' "All-Hazards Planning Reference Model" that
distinguishes three planning categories-Disaster Trigger Event, Man-Made Hazards,
and Vulnerability Factors; b) the generalization of their model to other
countries; and c) advocacy for environmental health end fate to be considered in
planning phases to minimize risk to environmental health. This article discusses
inconsistencies in disaster planning and nomenclature existing in the studied
materials and international guidance and proposes new opportunity for developing
predisaster risk assessment, risk communication, and prevention capacity
building.
PMID- 26427266
TI - What Is a Diplomate, and What Does It Do?
PMID- 26427267
TI - Equipping Environmental Health Workers With Environmental Assessment Tools.
PMID- 26427268
TI - A Millennial's Take on CDC's Environmental Public Health Tracking Network.
PMID- 26427269
TI - Outraged, Obligated, & Optimistic.
PMID- 26427270
TI - Should Substituted Decision-making Be Abolished?
PMID- 26427271
TI - Advance Directives in Some Western European Countries: A Legal and Ethical
Comparison between Spain, France, England, and Germany.
AB - We have studied national laws on advance directives in various Western European
countries: Romance-speaking countries (Italy, France, Portugal, and Spain),
English-speaking countries (Ireland and the United Kingdom), and German-speaking
countries (Austria, Germany, and Switzerland). We distinguish two potentially
complementary types of advance medical declaration: the 'living will' and the
nomination of a legal proxy. After examining the similarities and differences
between countries, we analyse in detail the legislation of four countries (Spain,
France, England, and Germany), since the other countries in this survey have
similar legal principles and/or a similar political approach. In conclusion, we
note that in all the countries examined, advance directives have been seen as an
instrument to enable the patient's right to self-determination. Notwithstanding,
in Romance-speaking countries, the involvement of physicians in the end-of-life
process and risks arising from the execution of advance directives were also
considered.
PMID- 26427272
TI - Medical Liability: The Current State of Italian Legislation.
PMID- 26427273
TI - Use of Force for Medical Purposes--A Danish Perspective.
PMID- 26427274
TI - European Court of Human Rights. ECHR 2015/15 Case of Ilievska v. The Former
Yugoslav Republic of Macedonia, 7 May 2015, no. 20136/11 (First Section).
PMID- 26427275
TI - European Court of Human Rights. ECHR 2015/16 Case of Lambert and Others v.
France, 5 June 2015, no. 46043/14 (Grand Chamber).
PMID- 26427276
TI - European Court of Justice. ECJ 2015/05, Geoffrey Leger v. Ministre des Affaires
sociales, de la Sante et des Droits des femmes, Etablissement francais du sang,
29 April 2015 (c-528/13).
PMID- 26427277
TI - [A literature review on the Messerer's fracture].
AB - The characteristic wedge-shaped fracture was first described by Messerer (1880)
and Bruns (1884) after performing experiments on long bones. Not much later,
Messerer (1885) formulated the forensic significance of the direct bending
fracture for the detection of the location and direction of blunt impact trauma.
He developed the basic biomechanical theory of the origin of this fracture type,
which is therefore called Messerer's fracture in the German-speaking world. In
the following decades, the findings concerning the origin, specificity and
forensic usability of Messerer's fractures were confirmed and supplemented by
experiments and case studies. For forensic examinations, it is important to bear
in mind that there are exceptions to the rule according to which the level of the
wedge-shaped fracture corresponds exactly to the point of impact. The possibility
of "false" or "reversed" wedges must also be considered. Already in the 19th
century, authors had pointed out the mechanism of indirect formation of wedge
shaped bone fragments. That is why a forensic examination always has to consider
the investigation results and medical findings in their entirety. Autopsy of
traffic victims is of paramount importance. It must include a thorough
examination of clothing, skin, soft tissues and skeletal system using special
preparation techniques. The examination of bone injuries in living victims also
requires special expertise. If properly applied, valuable results can be obtained
by the forensic expert from the wedge-shaped fracture. Until recently, Messerer's
fracture was a typical injury sustained by pedestrians hit by vehicles with
protruding frontal elements. In modern car production, not only the dimensions of
cars have been changed, but the front-end structures have also been modified, e.
g. by integrated bumpers. These constructional changes are likely to reduce the
frequency of narrow points of impact in collisions. However, further research on
the frequency and significance of Messerer's fractures in road traffic accident
victims is required.
PMID- 26427278
TI - [Reddish discoloration of the vascular intima in charred bodies].
AB - During the autopsy of fire victims, one often sees intensive reddening of the
inner vascular layers resembling changes due to putrefaction. To determine the
frequency of this phenomenon and the circumstances under which it occurs, in
particular the presence of putrescence, signs of vitality and the extent of
destruction by the fire, the fire fatalities autopsied at the Institutes of Legal
Medicine in Freiburg, Halle and Wurzburg were analyzed. In the concrete study,
259 fire deaths were investigated retrospectively and 21 prospectively. The study
material included 191 males and 68 females aged 0 to 93 years. Vital exposure to
the fire was found in 70%, perimortal exposure in 23 % and postmortem exposure in
7% of the cases. Red discoloration of the intima of the central vessels was seen
in 106 victims (41%). This finding is most likely caused by postmortem heat
induced hemolysis, which occurs when the temperature in the body rises above 52
degrees C due to the effect of external heat. Therefore, a reddish discoloration
of the intima cannot be regarded as sign of vitality.
PMID- 26427279
TI - [Diuretics and their potential effect on breath-alcohol concentration--a case
report].
AB - Many objections were raised to breath-alcohol analysis upon its introduction in
the field of traffic law enforcement in Germany, but in the meantime this issue
has become less relevant in forensic routine work. In the present case, the
defending lawyer claimed that the ethanol concentration in the blood and hence in
the breath of his client, which was 0.35 mg/l according to the Drager Alcotest
7110(r) Evidential and thus above the legal limit of 0.25 mg/l, had been changed
by diuretics taken 4 hours before the breath alcohol test, viz. 10 mg of
torasemide, a loop diuretic, and 50 mg of spironolactone, a competitive
aldosterone antagonist. According to the literature, the maximum urinary output
in healthy subjects within the first 4 hours after 10 mg torasemide was 1450 ml.
In patients suffering from heart failure, the urinary volume was reduced by a
factor of 2.5-3; after chronic intake of torasemide, water loss did not differ
from placebo. Spironolactone, which acts on the distal tubule, has little effect
on urinary output. In a publication, the loss of water in excess within 24 hours
was 90 ml. Co-administration of 100 mg spironolactone and 20 mg furosemide, which
roughly compares to 10 mg torasemide, resulted in a mean urinary volume of 1566
ml within the first 4 hours. In terms of the reported case and provided that no
compensatory fluid had been taken, a purely theoretical maximum shift of 0.007
mg/ may occur in the breath-alcohol concentration due to the smaller distribution
volume even considering maximum urinary excretion values. On the other hand,
already mild levels of dehydration may be associated with negative symptoms
affecting driving ability.
PMID- 26427280
TI - [Peranal exenteration of the intestine during a homicide].
AB - A 66-year-old female alcoholic was killed in a sexually motivated homicide. After
peranal insertion of the hand large parts of the intestine were torn from the
mesentery and pulled out through the anus. The findings are discussed and
compared with the pertinent literature.
PMID- 26427281
TI - [Wrong statement of manner of death after insufficient post-mortem examination].
AB - When death certificates already completed are submitted during forensic post
mortem examinations or autopsies, blatant errors are often found, especially with
regard to the classification of the manner of death. This is partly attributable
to insufficient knowledge of the classification criteria, but also to the fact
that the post-mortem examination was not properly performed and even clear signs
of unnatural death (e.g. a strangulation mark or sharp force injuries) are
overlooked. To avoid such misinterpretations, a thorough reformation of the post
mortem examination system and a regular continuing specialized training of the
physicians performing post-mortems seem necessary.
PMID- 26427282
TI - [Sexual assault during sleep: victim asleep/offender asleep--an update].
AB - The topic of sexual assault during sleep is discussed again on the basis of two
case reports and several incidents published in the media. The authors support
the assumption of Hohner and Pusche1 (2011). There is evidence that it is indeed
possible not to wake up during a sexual assault--even without being under the
influence of alcohol, illicit drugs or medication--and that a sexual assault
during sleep can pass unnoticed. In such cases the outcome of the criminal trial
often depends on the careful assessment of the expert, as the faculty of
imagination of those passing judgment varies greatly. Based on new findings
regarding sexsomnia, even sexual offenders may use the "sleepwalking defense" in
specific cases.
PMID- 26427283
TI - REVISED: Accreditation with Follow-up Survey and Preliminary Denial of
Accreditation Decision Processes for Organizations Undergoing Resurvey.
PMID- 26427284
TI - APPROVED: New Optional Perinatal Care Certification Program.
PMID- 26427285
TI - New Speak Up Video Educates Patients on Preparing for Surgery.
PMID- 26427286
TI - APPOINTED: Executive Vice President for Division of Healthcare Quality
Evaluation.
PMID- 26427287
TI - REVISED: Accreditation Decisions for Organizations Undergoing Initial Surveys.
PMID- 26427288
TI - [Gram positive multi-drug resistance: what probability and fear?].
AB - Antibiotic resistance in Gram-positive bacteria already has a significant impact
on morbidity and mortality. The situation is particularly alarming in the case of
methicillin-resistant Staphylococcus aureus and glycopeptide-resistant
Enterococcus faecium, which have shown an ability to spread to new ecological
niches and to generate new clones with both increased drug resistance and
increased virulence. The potential for genetic exchanges between these two
species raises the specter of highly resistant and virulent S. aureus strains.
PMID- 26427289
TI - [Innovative treatments for multidrug-resistant bacteria].
AB - The spread of multidrug-resistant bacteria has accelerated sharply in the last
decade. According to the World Health Organization they are responsible for an
estimated 25 000 deaths in Europe each year. In addition, few new antibiotics are
under development, raising the spectrum of a return to the "pre-antibiotic era".
Non antibiotic antibacterial agents have recently attracted renewed interest. The
most promising candidates are: i) phages (bacteria-infecting viruses) have been
widely used in Eastern European countries since the 1930s but come up against
logistic and regulatory obstacles due to the evolutionary nature of these
biologic agents, while convincing clinical data are lacking; ii) bacteriocines
are smallantibacterialpeptidesproducedby numerous bacteria; some have a rapid
bactericidal effect, good tolerability, and a limited impact on the commensal
flora; however, clinical use of bacteriocines is complicated by their fragility,
poor penetration, and substantial risk of resistance selection ; iii) antisense
oligonucleo tides act by inactivating genes through specific interaction with a
complementary DNA or RNA fragment, potentially allowing specific inhibition of
selected bacterial virulence factors. However, this therapeutic class may be more
suitable for viral or genetic diseases than for multidrug-resistant bacterial
infections, owing to the difficulty of delivering them inside bacteria.
PMID- 26427290
TI - [Anomalous aortic origin of coronary arteries: a frequent and curable cause of
sudden death].
AB - Anomalous aortic origin of coronary arteries is a congenital heart defect in
which one coronary artery arises from the opposite sinus (the left coronary
artery from the right coronary sinus, or the right coronary artery from the left
sinus). The initial segment of the abnormal artery courses between the great
arteries and is usually located within the aortic wall. These anomalies are far
from rare, affecting 0.1% to 0.3% of the population, and carry a high risk of
sudden cardiac death. It is thought that the main mechanism of cardiac death is
external compression of the abnormal coronary artery between the great arteries
as they expand during strenuous exercise. The risk of sudden death is
particularly high in patients with an anomalous left coronary artery or
associated anatomic lesions (stenotic intramural segment, slit-like deformation
of the ostium), and also in young athletes. A common presentation is sudden
unexplained death. The diagnosis can be made by echocardiographic examination.
Silent myocardial ischemia must be sought, with stress echocardiography and
stress nuclear imaging. Various surgical techniques have been described. Our own
technique involves the creation of a neo-ostium in the appropriate sinus.
Surgical treatment is relatively safe and provides satisfactory results, most
patients having no residual myocardial ischemia under stress. Surgery is
recommended for all patients with an anomalous left coronary artery, regardless
of symptom status, as well as for symptomatic patients with an anomalous right
coronary artery (aborted sudden death, symptoms under stress, myocardial ischemia
under stress). Because of the incidence and severity of these anomalies, careful
echocardiographic evaluation should be performed routinely, at least in young
athletes.
PMID- 26427291
TI - [Future of implantable electrical cardiac devices].
AB - Major improvements in implantable electrical cardiac devices have been made
during the last two decades, notably with the advent of automatic internal
defibrillation (ICD) to prevent sudden arrhythmic death, and cardiac
resynchronisation (CRT) to treat the discoordinated failing heart. They now
constitute a major therapeutic option and may eventually supersede drug therapy.
The coming era will be marked by a technological revolution, with improvements in
treatment delivery, safety and efficacy, and an expansion of clinical
indications. Leadless technologyfor cardiac pacemakers and defibrillators is
already in the pipeline, endovascular leads currently being responsible for most
long-term complications (lead failure, infection, vein thrombosis, etc.).
Miniaturized pacemakers based on nanotechnology can now be totally implanted
inside the right ventricle through the transvenous route, thus eliminating leads,
pockets and scarring In the same way, totally subcutaneous ICD systems are now
available, although they are currently only capable of delivering shocks, without
pacing (including antitachycardia pacing). In CRT optimised delivery is important
to improve clinical responses and to reduce the non-response rate (around 30 %
with current technology). Endocardial left ventricular pacing could be a solution
if it can be achieved at an acceptable risk. Multisite ventricular pacing is an
alternative. Besides CRT neuromodulation, especially by vagal stimulation, is
another important field of device researchfor heart failure. Preliminary clinical
results are encouraging.
PMID- 26427292
TI - [Cardiac rehabilitation: physiologic basis, beneficial effects and
contraindications].
AB - Cardiac rehabilitation can reduce morbidity and mortality cost-effectively among
patients with many types of cardiovascular disease yet is widely underutilized.
Rehabilitation is helpful not only for patients who have had myocardial
infarction but also for those with stable angina or congestive heart failure and
those who have undergone myocardial revascularization, transplantation, or valve
surgery. The beneficial effects of rehabilitation include a reduction in
mortality from cardiovascular disease, improved exercise tolerance, and fewer
cardiac symptoms. This method includes improved risk factor management, more
successful smoking cessation, better psychosocial well-being, and an increased
likelihood of return to work. Rehabilitation requires a multidisciplinary team
focusing on therapeutic education, individually tailored exercise, and
optimization of functional status and mental health. Current research trends in
this area include the evaluation of new secondary prevention modalities and
alternatives such as home-based rehabilitation.
PMID- 26427293
TI - [Benefits and indications of rehabilitation for coronary heart diseases].
AB - Cardiac rehabilitation (CR) is an essential element in the treatment of coronary
artery disease. It can be conducted on an inpatient or ambulatory basis in
cardiac rehabilitation units and includes complementary exercise training and a
therapeutic patient education (TPE) program. Rehabilitation can reduce the
occurrence of serious cardiac events and provide better control of cardiovascular
risk factors. All epidemiological surveys show that this approach is beneficial:
multidisciplinary care reduces mortality after myocardial infarction and improves
cardiac patients' lifestyles. Rehabilitation centers are the only structures able
to conduct 3- to 4-week program of cardiac training and TPE. Unfortunately, the
number of patients who participate in such programs is still too low, and cardiac
rehabilitation centers are underutilized (32 % in the French cohort of the
EUROASPIRE III study and about 15 % of all coronary patients). This situation is
regrettable, as all registers and epidemiological surveys have confirmed the
capacity of CR to improve exercise tolerance, the ischemic threshold, and
secondary prevention.
PMID- 26427294
TI - [Cannabis in France, new insights].
AB - France holds the record for cannabis use in Europe, especially among adolescents.
This drug of abuse is thus mainly used during a very sensitive period of brain
development, education, vehicle driving and development of life projects. In
addition, synthetic derivatives of tetrahydrocannabinol (THC), which are more
noxious than cannabis itself are now appearing on the market. Traficking and
cultivation for personnal use have intensified; products proposed for sale are
richer in THC; and some methods of consumption (e-cigarettes, vaporizers, water
pipes) increase the supply of THC to the lungs and thence to the body and brain.
It is in this context that attempts are being made to legalize this drug of
abuse. Other attempts are made to disguise it as a medication. Meanwhile, the
list of its psychic as well as physical damages grows longer, with some very
severe cases of major injuries. This evolution takes place in spite of numerous
warnings expressed by the French Academy of Medicine. Subsequently, it is
prompted to carefully and vigorously denounce these events. This will be the aim
of this thematic session.
PMID- 26427295
TI - [Neurobiology of endocannabinoids and central effects of tetrahydrocannabinol
contained in indian hemp].
AB - Tetrahydrocannabinol, the main psychotropic component of Cannabis indica, is an
addictive drug with multiple effects including both peripheral and central
damages. All these effects are due to interference with endocannabinoidergic
transmission. This endocannabinoid system subtly regulates many
physiologicalfunctions. This regulation involves various ligands derived from
arachidonic acid (anandamide, di-arachidonoylglycerol, virodhamin, noladin ether,
N arachidonoyl dopamine, etc.) which stimulate two main types of receptor CB1 in
the central nervous system and CB2 in the periphery. CB1 receptors are very
numerous and ubiquitous in the brain. They influence various important functions
(awakening, attention, delirium, hallucinations, memory, cognition, anxiety,
humor stability, motor coordination, brain maturation, etc.). Far from mimicking
endocannabinoids, THC caricatures their effects. It affects all brain structures,
simultaneously, intensely and durably, inducing down-regulation of CB1 receptors
and thereby reducing the effects of their physiological ligands. On account of
its exceptional lipophilia, THC accumulates for days and even weeks in the brain.
It is not a soft drug but rather a slow drug: its abuse induces long-lasting
modifications and deterioration of brain function, potentially leading to various
mental and psychiatric disorders.
PMID- 26427296
TI - [Tetrahydrocannabinol pharmacokinetics; new synthetic cannabinoids; road safety
and cannabis].
AB - Delta-9-tetrahydrocannabinol (THC) is the main psychoactive ingredient of
cannabis, a drug which is commonly smoked This paper focuses on the
pharmacokinetics of THC. The average THC content in cannabis plant material has
risen by a factor offour over the past 20 years, from 4% to 16%. This increase
has important implications not only for the pharmacokinetics but also for the
pharmacology of THC The mean bioavailability of THC in smoked cannabis is about
25%. In a cigarette containing 3.55% of THC, a peak plasma level of about 160
ng/mL occurs approximately 10 min after inhalation. THC is quickly cleared from
plasma in a multiphasic manner and is widely distributed to tissues, leading to
its pharmacologic effects. Body fat is a long-term storage site. This particular
pharmacokinetic behavior explains the lack of correlation between the THC blood
level and clinical effects, contrary to ethanol. The main THC metabolites are 11
OH-THC (the only active metabolite) and THC-COOH, which is eliminated in feces
and urine over several weeks. Therefore, abstinence can be established by
analyzing THC-COOH in urine, while blood THC analysis is used to confirm recent
exposure. Cannabis is the main illicit drug found among vehicle drivers. Various
traffic safety studies indicate that recent use of this drug at least doubles the
risk of causing an accident, and that simultaneous alcohol consumption multiplies
this risk by afactor of 14. Since 2009, synthetic cannabinoids have emerged on
the illicit drug market. These substances act on the same CB1 receptors as THC,
but with higher afinity. Their pharmacokinetics differs from that of THC, as they
are metabolized into multiple derivatives, most of which are more active than THC
itself.
PMID- 26427297
TI - [Cannabis-induced cognitive and psychiatric disorders].
AB - Several studies have shown that Delta-9-THC the main psychoactive constituent of
cannabis, can impair cognitive functions, especially attention, episodic memory,
working memory and executive functions. These impairments have been related to
the duration, frequency, dose and age at onset of cannabis use. Cognitive
deficits may disappear with abstinence, but abnormalities may be long-lasting in
subjects who began smoking cannabis before age 15. The lifetime prevalence of
cannabis use disorders is about 1% in the general population. The main
characteristics of cannabis use disorders are craving, persistent desire or
unsuccessful efforts to cut down or control cannabis use, and persistent
avoidance of familial, social occupational or recreational activities because of
cannabis use. Nine prospective longitudinal studies in the generalpopulation have
shown that cannabis use is associated with a two-fold increase in the risk of
psychotic disorders, particularly schizophrenia, compared to controls. The risk
of psychosis increases in a dose-related fashion. A higher risk of schizophrenia
is predicted by earlier onset of cannabis use. The effects of cannabis are
exerted primarily through THC interaction with cannabinoid (CB) 1 receptors in
the brain. Cannabis exposure may disrupt the last steps of brain maturation,
through the endocannabinoid system, thereby increasing the risk of psychosis
during adolescence.
PMID- 26427298
TI - [Cannabis use among children and adolescents: impacts and consequences].
AB - A health policy for the prevention and treatment of cannabis-related disorders is
urgently needed in France, given the high prevalence of cannabis use among
children and adolescents. Such a policy will require a better understanding of
the endo-cannabinoid system and the impact of exogenous cannabinoids in this
fragile population. The brain continues to undergo significant development until
the age of about 25 years, and cannabis consumption by young people therefore
carries specific risks of dependence (frequency and intensity), and of
neuroanatomical, cognitive and emotional damage. This article summarizes the
available data and offers a medical view of the risks and consequences of
cannabis use by children and adolescents.
PMID- 26427300
TI - Family group conferencing in dementia care: an exploration of opportunities and
challenges.
AB - BACKGROUND: The Family Group Conference (FGC) is an approach to partnership
working which brings together service users, their support network and care
professionals in a family-led decision making forum. Evidence, though limited,
indicates that that FGC can enhance outcomes for service providers and their
users. This study aimed to evaluate the impact of the pilot FGC service,
delivered to people with dementia and their families, in terms of the experience
of care provision by families and care professionals involved in the project.
METHODS: Focus group interviews were conducted with families and professionals
participating in the pilot intervention. RESULTS: FGC was perceived as having the
potential to positively impact service users, their families, service providers
and the wider culture of care. However, despite an overall positive evaluation
the participants identified a number of challenges related to service
implementation. Both the opportunities and challenges identified in this study
are discussed in the context of the existing international evidence base.
CONCLUSIONS: This study contributes to a better understanding of the
applicability of FGC as a strategy to support people with dementia and their
families. Although promising in terms of potential outcomes for service users and
providers, FGC presents challenges which need to be carefully managed in order to
secure maximum benefit to all parties.
PMID- 26427299
TI - [Issues surrounding the preservation and subsequent use of transsexual persons'
gametes].
AB - Some transsexual persons wish to have their gametes frozen before gender
transition, in order to preserve their fertility. This measure should be carried
out, in strict compliance with the law, in case of orchidectomy, oophorectomy or
hysterectomy However, as hormonal treatments do not irreversibly alter gonadal
function, the reproductive capacity of trans-sexual persons can be maintained by
avoiding surgical sterilization. There is therefore no obvious medical indication
for cryopreserving gametes or germinal tissue in the absence of surgical
sterilization. Moreover, the use of such cryopreserved gametes would, in
principle, be considered mainly by a same-sex couple, something that French law
currently prohibits. Regardless of these legal aspects, the issues surrounding
the use of cryopreserved gametes, and its consequences, must not be ignored. If
transsexual persons who are already parents may find ways of managing the change
in both their personal and parental identity, the use of gametes stored prior to
gender transition raises issues of identity whose consequences are difficult to
assess, especially for the future child. Cryopreservation of gametes or germinal
tissue cannot be undertaken without first considering whether their potential use
is in keeping with what is, at present, medically and legally possible. In any
case, it is up the physician to decide, on a case by case basis, whether or not
to implement cryopreservation, taking into account the situation of the persons
who request the procedure and their plans for parenthood.
PMID- 26427301
TI - A Comparison of the Use of Glottal Fry in the Spontaneous Speech of Young and
Middle-Aged American Women.
AB - OBJECTIVES/HYPOTHESIS: To compare vocal fry use in spontaneous speech of young
and middle-aged American women. STUDY DESIGN: This is a cross-sectional study.
METHODS: Subjects were 40 American women; 20 aged 18-25 years (mean = 22.9 years)
and 20 aged 35-50 years (mean = 43.4 years). Participants were asked to describe
all the steps involved in making a peanut butter and jelly sandwich and in doing
laundry. Acoustical analysis of selected parameters and sentence position of
vocal fry occurrences were performed. The acoustic parameters analyzed were mean,
minimum and maximum fundamental frequency (F0), glottal fry/minute ratio, and
sentence position of glottal fry. RESULTS: Values of minimum fundamental
frequency clearly show that there was vocal fry in the participants' spontaneous
speech samples. The average minimum F0 was 74.0 Hz (standard deviation [SD] =
5.6) for the younger women and 73.10 Hz (SD = 6.7) for the middle-aged women (P =
0.527). The mean glottal fry for the medial position and for the final position
was similar for both groups. The mean glottal fry/minute ratio for young women
was 13.8 (SD = 7.0), whereas for middle-aged women was 11.3 (SD = 7.5; P =
0.402). This study showed that all participants had at least one episode of
glottal fry in their spontaneous speech sample. CONCLUSIONS: Both groups
presented with vocal fry in their spontaneous speech, showing that vocal fry is
present in the speech of young and middle-aged women.
PMID- 26427302
TI - Three-dimensional ultrasound using the VOCAL technique for estimation of
reference values of fetal thigh volume in normally grown Egyptian fetuses from 20
to 41 weeks.
AB - OBJECTIVE: To establish the normal reference values for the fetal thigh volume
(FTV) of normally grown Egyptian fetuses using three-dimensional (3D) virtual
organ computer aided analysis (VOCAL) method. PATIENTS AND METHODS: A total of
334 Egyptian pregnant women carrying a singleton living normally grown fetus
between the 20th and the 41st weeks of gestation were enrolled in this cross
sectional study. FTV was measured using the 3D VOCAL method with 30 degrees
rotation. Estimated fetal weight (EFW) was calculated based on Hadlock formula.
RESULTS: FTV correlated strongly with gestational age (r = 0.921, p < 0.001) and
EFW (r = 0.891, p < 0.001). For clinical application, a nomogram of growth
percentiles of FTV was produced. CONCLUSION: Reference values of FTV between 20th
and 41st weeks of gestation in normally grown Egyptian fetuses were provided
using the 3D VOCAL method. These data may be helpful to assess fetal growth and
to diagnose deviation from normal.
PMID- 26427303
TI - Diffuse intestinal ganglioneuromatosis in the adult.
PMID- 26427304
TI - Measurement of cardiac index and stroke volume using electrical cardiometry
before and after administration of adenosine in a 6-year-old patient with
supraventricular tachycardia.
AB - We report the case of a 6-year-old boy who developed a supraventricular
tachycardia during an upper endoscopy while under general anesthesia. A
noninvasive electrical cardiometry device was applied to the patient, and cardiac
index and stroke volume were measured before and after the administration of
adenosine. Cardiac index fell 41% (P < .0001) after adenosine was given,
highlighting the known interdependence between cardiac output and heart rate in
the pediatric patient. Stroke volume decreased 9% (P = .0002) after adenosine
arrested the tachycardia, lending support to an increasing body of data that
suggests that heart rate itself can augment contractility.
PMID- 26427305
TI - Length of postanesthetic care unit stay in elderly patients after general
anesthesia: a randomized controlled trial comparing desflurane and sevoflurane.
AB - OBJECTIVE: The purpose of this study was to compare the length of postanesthetic
care unit (PACU) stay and recovery profiles of elderly patients after general
anesthesia between sevoflurane and desflurane. DESIGN: Randomized, double-blind,
controlled clinical trial. SETTING: Tertiary care hospital, university hospital.
PATIENTS: Eighty elderly patients undergoing nonemergency surgery under general
anesthesia. INTERVENTION: Patients were randomly allocated into 2 groups:
sevoflurane group (n = 38) and desflurane group (n = 42) in a double-blind
manner. All of the patients underwent general anesthesia with oral endotracheal
intubation using the same induction, muscle relaxants, and narcotics medication.
When the operation was finished, the volatile agent was discontinued and muscle
relaxation was reversed. MEASUREMENT: The length of PACU stay was recorded as the
primary outcome. The recovery profiles (time to open eyes, time to follow to
commands, and time to extubation) were assessed. MAIN RESULTS: There was no
significance between the groups in age, sex, body mass index, American Society of
Anesthesiologists physical status, type of surgery, duration of anesthesia,
perioperative use of fentanyl, or blood loss. The length of PACU stay was not
significantly different in the patients who recovered from sevoflurane (49.4 +/-
23.1 minutes) or desflurane (50.1 +/- 25.8 minutes) general anesthesia.
Desflurane was significantly associated with faster early recovery than
sevoflurane measured by time to open eyes (7.5 +/- 3.4 vs 9.6 +/- 4.6 minutes)
and time to follow commands (9.0 +/- 3.3 vs 11.2 +/- 5.1 minutes), respectively.
CONCLUSION: Desflurane was more associated with a faster early recovery (time to
open the eyes and follow commands) than sevoflurane in elderly patients after
general anesthesia. However, the length of PACU stay was similar in both groups.
PMID- 26427306
TI - Effects of vacuum suctioning and strategic drape tenting on oxygen concentration
in a simulated surgical field.
AB - STUDY OBJECTIVE: To investigate the isolated and combined effects of vacuum
suctioning and strategic drape tenting on oxygen concentration in an experimental
setting. DESIGN: Experimental. SETTING: Clinical simulation center of a
university-affiliated hospital. PARTICIPANTS: Mannequin simulation of a patient
undergoing facial surgery under sedation anesthesia. Supplemental oxygen was
delivered via nasal cannula. INTERVENTIONS: Vacuum suctioning and strategic drape
tenting. MEASUREMENTS: The experimental trials entailed measuring oxygen
concentration around the nasal cannula continuously either in the presence or
absence of a standard operating room vacuum suction system and strategic tenting
of surgical drapes. The primary outcome was the time required for oxygen
concentration to reach 21%. MAIN RESULTS: In the control group (without suction
or strategic tenting), a mean time of 180 seconds elapsed until the measured
oxygen concentration reached 21% after cessation of oxygen delivery. Use of a
vacuum suction device alone (110 seconds; P < .01) or in combination with
strategic tenting (110 seconds; P < .01) significantly reduced this time. No
significant benefit was seen when tenting was used alone (160 seconds; P < .30).
CONCLUSION: Use of a vacuum suction device during surgery will lower local oxygen
concentration, and this in turn may decrease the risk of operating room fires.
Although strategic tenting of surgical drapes has a theoretical benefit to
decreasing the pooling of oxygen around the surgical site, further investigation
is necessary before its routine use is recommended.
PMID- 26427307
TI - A comparison of ultrasound alone vs ultrasound with nerve stimulation guidance
for continuous femoral nerve block in patients undergoing total knee
arthroplasty.
AB - STUDY OBJECTIVE: To compare analgesic efficacy of ultrasound (US) guidance alone
and US guidance combined with nerve stimulation (NS) for continuous femoral nerve
block (CFNB) in patients undergoing total knee arthroplasty (TKA). DESIGN:
Prospective, randomized double-blind trial. SETTING: Postanesthesia care unit and
general ward. PATIENTS: Fifty American Society of Anesthesiologist physical
status I to II patients undergoing TKA under spinal anesthesia. INTERVENTIONS: In
group A (n = 25), an 18-gauge Tuohy needle was directed at the lower mid-part of
the femoral nerve, and a nonstimulating catheter was inserted through the needle
under US guidance. In group B (n = 25), an 18-gauge Tuohy needle and stimulating
catheter were directed to the lower part of femoral nerve under US guidance, and
quadriceps muscle contraction was checked using NS. All patients received a 20-mL
loading dose of 0.2% ropivacaine, a continuous infusion of 4 mL/h, and a 4-mL
bolus of 0.2% ropivacaine with a lockout time of 60 minutes for patient
controlled analgesia. MEASUREMENTS: The primary outcome was resting and
exercising pain quality assessed by numeric rating scale. Other outcomes included
procedure time for correct catheter placement, block failure rate, patient
satisfaction for postoperative pain control, total dose of local anesthetic,
additional opioid requirement, and adverse effects postoperatively. MAIN RESULTS:
There were no significant differences between groups in resting and exercising
numeric rating scale. Procedure times were longer in group B than group A (P <
.05). There were no significant differences between groups in block failure rate
or other outcomes. CONCLUSIONS: US-guided CFNB was associated with similar
analgesic efficacy and block failure rate and reduced procedure time compared to
US with NS guidance for CFNB in patients undergoing TKA.
PMID- 26427308
TI - Possible missed diagnosis of Ureaplasma spp infection in a case of fatal
hyperammonemia after repeat renal transplantation.
PMID- 26427309
TI - The impact of watching educational video clips on analogue patients'
physiological arousal and information recall.
AB - OBJECTIVE: Investigating the influence of watching three educational patient
provider interactions on analogue patients' emotional arousal and information
recall. METHODS: In 75 analogue patients the emotional arousal was measured with
physiological responses (electrodermal activity and heart rate) and self-reported
arousal. RESULTS: A moderate increased level of physiological arousal was
measured but not too much to inflict emotional distress. Recall of information
was within the pursued range. CONCLUSION: Hence, physiological arousal is not
expected to hinder the goals we pursue with our online intervention. PRACTICE
IMPLICATIONS: Still, developers and researchers should remain attentive to the
self-reported (conscious) and hidden (subconscious) emotions evoked by the
content of educational video clips presented in self-help interventions. A
moderate increased level of arousal is preferred to increase the learning
capacity. However, too much arousal may decrease the learning capacity and may
cause distress, which should obviously be avoided for ethical reasons.
PMID- 26427310
TI - Keep Europe alive.
PMID- 26427312
TI - Electrochemical Sensor for Lead Cation Sensitized with a DNA Functionalized
Porphyrinic Metal-Organic Framework.
AB - An efficient electrochemical sensor was presented for lead cation detection using
a DNA functionalized iron-porphyrinic metal-organic framework (GR-5/(Fe-P)n-MOF)
as a probe. The newly designed probe showed both the recognition behavior of GR-5
to Pb(2+) with high selectivity and the excellent mimic peroxidase performance of
(Fe-P)n-MOF. In the presence of Pb(2+), GR-5 could be specifically cleaved at the
ribonucleotide (rA) site, which produced the short (Fe-P)n-MOF-linked
oligonucleotide fragment to hybridize with hairpin DNA immobilized on the surface
of screen-printed carbon electrode (SPCE). Because of the mimic peroxidase
property of (Fe-P)n-MOF, enzymatically amplified electrochemical signal was
obtained to offer the sensitive detection of Pb(2+) ranging from 0.05 to 200 nM
with a detection limit of 0.034 nM. In addition, benefiting from the Pb(2+)
dependent GR-5, the proposed assay could selectively detect Pb(2+) in the
presence of other metal ions. The SPCE based electrochemical sensor along with
the GR-5/(Fe-P)n-MOF probe exhibited the advantages of low-cost, simple
fabrication, high sensitivity and selectivity, providing potential application of
on-site and real-time Pb(2+) detection in complex media.
PMID- 26427311
TI - Antibacterial and protein-repellent orthodontic cement to combat biofilms and
white spot lesions.
AB - OBJECTIVES: White spot lesions are the most undesired side-effect of fixed
orthodontic treatments. The objectives of this study were to combine
nanoparticles of silver (NAg) with 2-methacryloyloxyethyl phosphorylcholine (MPC)
to develop a modified resin-modified glass ionomer cement (RMGI) as orthodontic
cement with double benefits of antibacterial and protein-repellent capabilities
for the first time. METHODS: NAg and MPC were incorporated into a commercial
RMGI. Another commercial orthodontic adhesive also served as control. Enamel
shear bond strengths (SBS) were determined. Protein adsorption was measured via a
micro bicinchoninic acid method. A dental plaque microcosm biofilm model with
human saliva as inoculum was tested. Biofilms adherent on the cement samples and
planktonic bacteria in the culture medium away from the cement surfaces were both
evaluated for bacterial metabolic activity, colony-forming units (CFU), and
lactic acid production. RESULTS: Adding 0.1% NAg and 3% MPC to RMGI, and water
aging for 30 days, did not adversely affect the SBS, compared to the unmodified
RMGI control (p>0.1). The modified RMGI containing 0.1% NAg and 3% MPC achieved
the greatest reduction in protein adsorption, bacterial adhesion, CFU, metabolic
activity and lactic acid production. The RMGI containing 0.1% NAg and 3% MPC
inhibited not only the bacteria on its surface, but also the bacteria away from
the surface in the culture medium. CONCLUSIONS: The incorporation of double
agents (antibacterial NAg+protein-repellent MPC) into RMGI achieved much stronger
inhibition of biofilms than using each agent alone. The novel antibacterial and
protein-repellent RMGI with substantially-reduced biofilm acids is promising as
an orthodontic cement to combat white spot lesions in enamel.
PMID- 26427313
TI - Socio-economic inequalities in tobacco-related diseases in Portugal: an
ecological approach.
AB - OBJECTIVES: The existence of socio-economic (SE) inequalities in smoking is well
demonstrated, but less is known about its consequences. This study measures SE
inequalities in the prevalence of tobacco-related diseases (TRD) in Portugal,
using a new area-based SE indicator. STUDY DESIGN: Ecological study. METHODS: In
patient data were used to identify TRD discharges at all Portuguese NHS hospitals
for the year 2011. The definition of TRD incorporates malignant cancers,
cardiovascular diseases, cerebrovascular diseases and respiratory diseases. We
created an area-based SE indicator on the basis of census data, using factor
analyses. The association between the prevalence of TRD and the SE indicators was
measured using Generalized Linear Models. The spatial correlation of this
indicator was assessed using variograms. RESULTS: Two area-based SE factors were
identified at the parish level, reflecting (i) social position (education and
occupation); and (ii) deprivation (overcrowding and manual occupations). Upper
social-class areas were associated with a lower prevalence of malignant cancers,
cardiovascular, and respiratory diseases. CONCLUSION: We found significant
inequalities in TRDs across Portuguese parishes using a newly created area-based
SE indicator reflecting several SE dimensions. This result emphasizes that
inequalities in smoking are reflected in inequalities in health, and should be
tackled through equality-oriented area-based tobacco policies.
PMID- 26427314
TI - Beyond the Golden Era of public health: charting a path from sanitarianism to
ecological public health.
AB - The paper considers the long-term trajectory of public health and whether a
'Golden Era' in Public Health might be coming to an end. While successful
elements of the 20th century policy approach need still to be applied in the
developing world, two significant flaws are now apparent within its core
thinking. It assumes that continuing economic growth will generate sufficient
wealth to pay for the public health infrastructure and improvement needed in the
21st century when, in reality, externalised costs are spiralling. Secondly, there
is evidence of growing mismatch between ecosystems and human progress. While 20th
century development has undeniably improved public health, it has also undermined
the capacity to maintain life on a sustainable basis and has generated other more
negative health consequences. For these and other reasons a rethink about the
role, purpose and direction of public health is needed. While health has to be at
the heart of any viable notion of progress the dominant policy path offers new
versions of the 'health follows wealth' position. The paper posits ecological
public health as a radical project to reshape the conditions of existence. Both
of these broad paths require different functions and purposes from their
institutions, professions and politicians. The paper suggests that eco-systems
pressures, including climate change, are already adding to pressure for a change
of course.
PMID- 26427315
TI - The need to improve implementation and use of lifestyle surveillance systems for
planning prevention activities: an analysis of the Italian Regions.
AB - OBJECTIVES: To describe the level of use of lifestyle surveillance systems in
Italy and to identify predictors of their use by the Italian Regions for planning
and monitoring purposes. STUDY DESIGN: Data were extracted from the 19 Regional
Prevention Plans (RPPs) and the health promotion and prevention projects included
in them developed by the Italian Regions within the National Prevention Plan 2010
2013. METHODS: The 19 RPPs and the 702 projects were appraised using a tool
specifically developed for the purpose. Multiple logistic regression was
performed to identify predictors of use of surveillance systems in the 359
projects that could use them. RESULTS: The analysis of regional epidemiological
contexts does not always rely upon surveillance system data and there were too
few projects aimed at the maintenance and the development of these systems.
Moreover, fewer than half of projects that could have used surveillance systems
for planning and evaluation procedures actually did so, despite the potential
value of these data. There was a statistically significant association between
Regional Health Care Expenditure (RHCE) and the use of surveillance system data
for planning and/or evaluation of the projects (OR 7.81, 95% CI 2.86-21.29).
CONCLUSIONS: Use of surveillance systems for regional prevention planning in
Italy is not optimal due to late implementation, presence of different data
collecting systems and RGDP inequalities. There is a pressing need for full
implementation of surveillance systems to allow better definition of the
priorities and objectives of public health interventions.
PMID- 26427316
TI - Functional characterization of 12 allelic variants of CYP2C8 by assessment of
paclitaxel 6alpha-hydroxylation and amodiaquine N-deethylation.
AB - Cytochrome P450 2C8 (CYP2C8) is one of the enzymes primarily responsible for the
metabolism of many drugs, including paclitaxel and amodiaquine. CYP2C8 genetic
variants contribute to interindividual variations in the therapeutic efficacy and
toxicity of paclitaxel. Although it is difficult to investigate the enzymatic
function of most CYP2C8 variants in vivo, this can be investigated in vitro using
recombinant CYP2C8 protein variants. The present study used paclitaxel to
evaluate 6alpha-hydroxylase activity and amodiaquine for the N-deethylase
activity of wild-type and 11 CYP2C8 variants resulting in amino acid
substitutions in vitro. The wild-type and variant CYP2C8 proteins were
heterologously expressed in COS-7 cells. Paclitaxel 6alpha-hydroxylation and
amodiaquine N-deethylation activities were determined by measuring the
concentrations of 6alpha-hydroxypaclitaxel and N-desethylamodiaquine,
respectively, and the kinetic parameters were calculated. Compared to the wild
type enzyme (CYP2C8.1), CYP2C8.11 and CYP2C8.14 showed little or no activity with
either substrate. In addition, the intrinsic clearance values of CYP2C8.8 and
CYP2C8.13 for paclitaxel were 68% and 67% that of CYP2C8.1, respectively. In
contrast, the CLint values of CYP2C8.2 and CYP2C8.12 were 1.4 and 1.9 times
higher than that of CYP2C8.1. These comprehensive findings could inform for
further genotype-phenotype studies on interindividual differences in CYP2C8
mediated drug metabolism.
PMID- 26427317
TI - Editorial for the Special Issue: Toxins 2015 proceedings.
PMID- 26427318
TI - Synergistic effect of artocarpin on antibacterial activity of some antibiotics
against methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and
Escherichia coli.
AB - CONTEXT: Antibacterial resistance has dramatically increased and resulted in
serious health problems worldwide. One appealing strategy to overcome this
resistance problem is the use of combinations of antibacterial compounds to
increase their potency. OBJECTIVE: The objective of this study is to determine
the synergistic effects of artocarpin for ampicillin, norfloxacin, and
tetracycline against methicillin-resistant Staphylococcus aureus (MRSA) as well
as the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli.
MATERIALS AND METHODS: A broth microdilution method (1.95-250 ug/mL) was used to
determine the minimum inhibitory concentration (MIC) of artocarpin and the
antibiotics. Any synergistic effects were evaluated at their own MIC using the
checkerboard method and a time-kill assay at 37 degrees C for 24 h. RESULTS AND
DISCUSSION: Artocarpin showed antibacterial activity against MRSA and E. coli
with an MIC value of 62.5 ug/mL, and against P. aeruginosa with an MIC value of
250 ug/mL. The interaction of artocarpin with all tested antibiotics produced
synergistic effects against MRSA with a fractional inhibitory concentration index
(FICI) of 0.15-0.37. In addition, a combination of artocarpin and norfloxacin
showed a synergistic effect against E. coli with an FICI value of 0.37, while the
combinations of artocarpin and tetracycline as well as artocarpin and norfloxacin
exhibited synergy interactions against P. aeruginosa with FICI values of 0.24 and
0.37, respectively. Time-kill assays indicated that artocarpin enhanced the
antimicrobial activities of tetracycline, ampicillin, and norfloxacin against
MRSA as well as Gram-negative bacteria.
PMID- 26427319
TI - Quantitative Assessment of Cardiac Function in Fetuses of Women with Maternal
Gestational Thyroid Dysfunction Using VVI Echocardiography.
AB - BACKGROUND: The study aimed to investigate the clinical value of velocity vector
imaging (VVI) in assessing heart function in fetuses of pregnant women with
thyroid dysfunction. The inter-observer and intra-observer variability was
assessed for all VVI parameters observed. MATERIAL AND METHODS: The participants
were enrolled from singleton pregnant women with gestational ages ranging 24+0 to
40+1 weeks who visited the Department of Obstetrics and Gynecology at the
Affiliated Hospital of Qingdao University, China, for prenatal care from July
2011 to February 2014. Digital 2-dimensional (2D) dynamic 4-chamber images of the
heart were collected. A total of qualified 226 images from 125 fetuses of
pregnant women with normal thyroid (control group), 64 fetuses of pregnant women
with hypothyroidism (hypothyroidism group), and 37 fetuses of pregnant women with
hyperthyroidism (hyperthyroidism group) were interrogated offline using VVI
software. The echocardiographic parameters including the myocardium peak systolic
velocity (Vs), peak diastolic velocity (Vd), peak systolic strain (S), peak
systolic strain rate (SRs), peak diastolic strain rate (SRd) of RV and LV, were
obtained from the velocity curves of 2D myocardial motion. The heart rate was
measured using a virtual M-mode algorithm built into the software. RESULTS: The
study found that the longitudinal Vs and Vd of both ventricles in the control
group gradually decreased from basal segments to apical segments and
significantly increased over the gestation. S, SRs, and SRd of both ventricles
remained stable after middle gestation. Compared with the control group, the
hypothyroidism and hyperthyroidism groups exhibited significantly reduced S, SRs,
and SRd, even for fetuses at 24-weeks gestation. There were no significant
differences in global Vs and global Vd between the control group and the
hyperthyroidism or hypothyroidism groups. CONCLUSIONS: The thyroid dysfunction of
pregnant women may damage fetal heart function, and VVI could be a sensitive
technique to measure the variation of fetal heart function.
PMID- 26427320
TI - Speedy standing wave design of size-exclusion simulated moving bed: Solvent
consumption and sorbent productivity related to material properties and design
parameters.
AB - Size-exclusion simulated moving beds (SEC-SMB) have been used for large-scale
separations of linear alkanes from branched alkanes. While SEC-SMBs are orders of
magnitude more efficient than batch chromatography, they are not widely used. One
key barrier is the complexity in design and optimization. A four-zone SEC-SMB for
a binary separation has seven material properties and 14 design parameters (two
yields, five operating parameters, and seven equipment parameters). Previous
optimization studies using numerical methods do not guarantee global optima or
explicitly express solvent consumption (D/F) or sorbent productivity (PR) as
functions of the material properties and design parameters. The standing wave
concept is used to develop analytical expressions for D/F and PR as functions of
14 dimensionless groups, which consist of 21 material and design parameters. The
resulting speedy standing wave design (SSWD) solutions are simplified for two
limiting cases: diffusion or dispersion controlled. An example of SEC-SMB for
insulin purification is used to illustrate how D/F and PR change with the
dimensionless groups. The results show that maximum PR for both diffusion and
dispersion controlled systems is mainly determined by yields, equipment
parameters, material properties, and two key dimensionless groups: (1) the ratio
of step time to diffusion time and (2) the ratio of diffusion time to pressure
limited convection time. A sharp trade off of D/F and PR occurs when the yield is
greater than 99%. The column configuration for maximum PR is analytically related
to the diffusivity ratio and the selectivity. To achieve maximum sorbent
productivity, one should match step time, diffusion time, and pressure-limited
convection time for diffusion controlled systems. For dispersion controlled
systems, the axial dispersion time should be about 10 times the step time and
about 50 times the pressure-limited convection time. Its value can be estimated
from given yields, material properties, and column configuration. Among the
material properties, selectivity and particle size have the largest impact on D/F
and PR. Particle size and 14 design parameters can be optimized for minimum D/F,
maximum PR, or minimum cost on a laptop computer.
PMID- 26427321
TI - Gas chromatography with tandem differential mobility spectrometry of fatty acid
alkyl esters and the selective detection of methyl linolenate in biodiesels by
dual-stage ion filtering.
AB - Alkyl esters of fatty acids (FAAEs) with carbon numbers from 8 to 20 formed
protonated monomers and proton bound dimers through atmospheric pressure chemical
ionization reactions and these gas ions were characterized for their field
dependent mobility coefficients using differential mobility spectrometry (DMS).
Separation of ion peaks with a vapor modifier was achieved for ions with masses
of 317-1033 Da though the differences in these coefficients and the resolution of
ion peaks decreased proportionally with increased ion mass. Differences in
dispersion curves were sufficient to isolate ions from specific FAAEs in the
effluent of a gas chromatograph by dual stage ion filtering using a tandem DMS
detector. Methyl linolenate was isolated from nearby eluting methyl oleate,
methyl stearate and methyl linoleate within analysis times of 10s without
measureable complications from charge suppression in the ion source or leakage in
filtering of ions with close proximity of dispersion behavior.
PMID- 26427322
TI - Reversed-phase chromatography in extended-nano space for the separation of amino
acids.
AB - In this work we used reversed-phase chromatography in extended-nano channels to
separate amino acids. A hydrophobic surface modification of extended-nano
channels was established. A sample mixture of fluorescein and sulforhodamine B
(0.5 and 0.05mM respectively) was used for the demonstration of a reversed-phase
separation mode. A small amount of sample band (30fL) was injected into the
separation channel, and two compounds were successfully separated. The maximum
theoretical plate number of sulforhodamine B was 300,000plates/m. Two sets of 3
amino acids (3.75mM each) were separated using 0.01M citrate buffer (pH 5.5) with
0.01M sodium perchlorate and 12 and 25% of acetonitrile as a mobile phase. A
successful separation (320,000plates/m with plate height of 3.2MUm for serine)
was accomplished.
PMID- 26427323
TI - Evaluation of multistep derivatization methods for identification and
quantification of oxygenated species in organic aerosol.
AB - Two, 3-step methods for derivatizing mono- and multi-functional species with
carbonyl (CO), carboxylic acid (-COOH), and alcohol (-OH) moieties were compared
and optimized. In Method 1, the CO, -COOH, and -OH moieties were converted (1) to
methyloximes (R-CN-OCH3) with O-methylhydroxylamine hydrochloride (MHA), (2) to
methyl esters (OC-R-OCH3) with (trimethylsilyl)diazomethane in methanol
(TMSD/MeOH), and (3) to trimethylsilyl ethers [R-OSi(CH3)3] with N,O
bis(trimethylsilyl)-trifluoroacetamide (BSTFA) containing 1%
trimethylchlorosilane (TMCS), respectively. Steps 1 and 3 of both methods were
identical; however, in Step 2 of Method 2, -COOH moieties were derivatized with
10% (v/v) boron trifluoride (BF3) in MeOH or n-butanol (n-BuOH). The BF3/MeOH and
BF3/n-BuOH were ineffective at converting species with more than 2-OH moieties.
Average standard deviations for derivatization of 36 model compounds by the 3
step methods using TMSD/MeOH and BF3/(MeOH) were 7.4 and 14.8%, respectively.
Average derivatization efficiencies for Methods 1 and 2 were 88.0 and 114%,
respectively. Despite the lower average derivatization efficiency of Method 1,
distinct advantages included a greater certainty of derivatization yield for the
entire suite of mono- and multi-functional species and fewer processing steps for
sequential derivatization. Detection limits for Method 1 using GC*GC-ToF-MS were
0.3-54pgm(-3). Approximately 100 oxygenated organic species were identified and
quantified in aerosol filtered from 39m(3) of air in an urban location. Levels of
species were 0.013-17ngm(-3) and were nearly all above the Method 1 limit of
detection.
PMID- 26427324
TI - An improved design of spiral tube assembly for separation of proteins by high
speed counter-current chromatography.
AB - A new spiral tube assembly was designed to improve the column capacity and
partition efficiency for protein separation. This spiral tube assembly has
greater column capacity than the original tubing because of an increase in radial
grooves from 4 to 12 to accommodate more spiral layers and 12 narrow spots
instead of 4 in each circular loop to interrupt the laminar flow that causes
sample band broadening. Standard PTFE tubing (1.6mm ID) and the modified flat
twisted tubing were used as the separation column. The performances of both
assemblies were compared for separating three stable test proteins including
cytochrome c, myoglobin, and lysozyme using a two phase aqueous-aqueous solvent
system composed of polyethylene glycol 1000 (12.5% w/w) and dibasic potassium
phosphate (12.5% w/w). All samples were run at 1, 2, 3, and 5mL/min at both
800rpm and 1000rpm. The separation of these three protein samples produced high
stationary phase retentions at 1, 2, and 3mL/min, yet separated efficiently at
5mL/min in 40min. After comparing the separation efficiency in terms of the peak
resolutions, theoretical plate numbers, and separation times, it was determined
that the flat-twisted tubing was more effective in separating these protein
samples. In order to validate the efficacy of this novel assembly, a mixture of
five protein samples (cytochrome c, myoglobin, ovalbumin, lysozyme, and
hemoglobin) were separated, under the optimal conditions established with these
three protein samples, at 1mL/min with a revolution speed of 1000rpm. There were
high stationary phase retentions of around 60%, with effective separations,
demonstrating the efficiency of the flat-twisted spiral tube assembly. The
separation time of 6h was a limitation but can potentially be shortened by
improving the strength of the column that will permit an increase in revolution
speed and flow rate. This novel spiral separation column will allow rapid and
efficient separation of mixtures with high yield of the constituent components.
PMID- 26427325
TI - Imidazole-free purification of His3-tagged recombinant proteins using ssDNA
aptamer-based affinity chromatography.
AB - Immobilized metal ion affinity chromatography (IMAC) is widely used for the
purification of many different His6-tagged recombinant proteins. On the one hand,
it is a powerful technique but on the other hand it has its disadvantages. In
this report, we present the development of a unique ssDNA aptamer for the
purification of His3-tagged recombinant proteins. Our study shows that stability
of the His3-tag/H3T aptamer complex can be controlled by the sodium ion
concentration. Based on this feature, we demonstrate that H3T aptamer resin was
successfully employed for the purification of three out of four tested His3
tagged recombinant proteins from an E. coli total protein extract using imidazole
free buffers. Finally, we show that the purity of His3-tagged proteins is
superior when purified with the help of the H3T aptamer in comparison with Ni-NTA
resin.
PMID- 26427326
TI - Simultaneous determination of fluoroquinolones in environmental water by liquid
chromatography-tandem mass spectrometry with direct injection: A green approach.
AB - This work describes an on-line multi-residue method for simultaneous
quantification of ciprofloxacin, enrofloxacin, gemifloxacin, moxifloxacin,
norfloxacin and ofloxacin in superficial and wastewater samples. For that, an
octyl restricted-access media bovine serum albumin column (RAM-BSA C8) was used
for sample clean-up, enrichment and analysis with quantitation carried out by
tandem mass spectrometry. For water samples volumes of only 500MUL the method
provided good selectivity, extraction efficiency, accuracy, and precision with
quantification limits in the order of 20-150ngL(-1). Out of the six
fluoroquinolones only ciprofloxacin (195ngL(-1)) and norfloxacin (270ngL(-1))
were quantified in an influent sample of the wastewater treatment plant (WWTP) of
Sao Carlos (SP, Brazil). None were found in the superficial water samples
analyzed. The capability of injecting native sample in an automated mode provides
high productivity and represents a greener approach in environmental sample
analysis.
PMID- 26427327
TI - Characterization of goat colostrum oligosaccharides by nano-liquid chromatography
on chip quadrupole time-of-flight mass spectrometry and hydrophilic interaction
liquid chromatography-quadrupole mass spectrometry.
AB - A detailed qualitative and quantitative characterization of goat colostrum
oligosaccharides (GCO) has been carried out for the first time. Defatted and
deproteinized colostrum samples, previously treated by size exclusion
chromatography (SEC) to remove lactose, were analyzed by nanoflow liquid
chromatography-quadrupole-time of flight mass spectrometry (Nano-LC-Chip-Q-TOF
MS). Up to 78 oligosaccharides containing hexose, hexosamine, fucose, N
acetylneuraminic acid or N-glycolylneuraminic acid monomeric units were
identified in the samples, some of them detected for the first time in goat
colostra. As a second step, a hydrophilic interaction liquid chromatography
coupled to mass spectrometry (HILIC-MS) methodology was developed for the
separation and quantitation of the main GCO, both acidic and neutral
carbohydrates. Among other experimental chromatographic conditions, mobile phase
additives and column temperature were evaluated in terms of retention time,
resolution, peak width and symmetry of target carbohydrates. Narrow peaks (wh:
0.2-0.6min) and good symmetry (As: 0.8-1.4) were obtained for GCO using an
acetonitrile:water gradient with 0.1% ammonium hydroxide at 40 degrees C. These
conditions were selected to quantify the main oligosaccharides in goat colostrum
samples. Values ranging from 140 to 315mgL(-1) for neutral oligosaccharides and
from 83 to 251mgL(-1) for acidic oligosaccharides were found. The combination of
both techniques resulted to be useful to achieve a comprehensive characterization
of GCO.
PMID- 26427328
TI - Analysis of black pepper volatiles by solid phase microextraction-gas
chromatography: A comparison of terpenes profiles with hydrodistillation.
AB - Solid phase microextraction (SPME) is widely used in food flavor compounds
analysis in majority for profiling volatile compounds. Based on such profiles
conclusions are often drawn concerning the percentage composition of volatile
compounds in particular food, spices or raw materials. This paper focuses on the
usefulness of SPME for the profiling of volatile compounds from spices using
black pepper as an example. SPME profiles obtained in different analytical
conditions were compared to the profile of pepper volatiles obtained using
hydrodistillation in Clevenger apparatus. The profiles of both monoterpenes and
sesquiterpenes of black pepper were highly dependent on sample weight (0.1 and 1g
samples were tested), and extraction time (durations from 2 to 120min were
tested), regardless of the SPME fiber used (PDMS and CAR/PDMS coatings were
used). The characteristic phenomenon for extraction from dry ground pepper was
the decrease of monoterpenes % share in volatiles with increasing extraction
times, whereas at the same time the % contents of sesquiterpenes increased.
Addition of water to ground pepper substantially changed extraction kinetics and
mutual proportions of mono to sesquiterpenes compared to dry samples by
minimizing changes in mono- to sesquiterpenes ratio in different extraction
times. Obtained results indicate that SPME can be a fast extraction method for
volatiles of black pepper. Short extraction times (2-10min) in conjunction with
the fast GC analysis (2.1min) proposed here may offer fast alternative to
hydrodistillation allowing black pepper terpenes characterization.
PMID- 26427330
TI - Medicinal leech therapy: New life for an ancient treatment.
PMID- 26427331
TI - Melioidosis in the non-endemic setting: Not only in diabetic travelers returning
from Southeast Asia.
PMID- 26427333
TI - Correction: Highly regio- and stereoselective synthesis of alkenylboronic esters
by copper-catalyzed boron additions to disubstituted alkynes.
AB - Correction for 'Highly regio- and stereoselective synthesis of alkenylboronic
esters by copper-catalyzed boron additions to disubstituted alkynes' by Hye Ryung
Kim et al., Chem. Commun., 2011, 47, 2943-2945.
PMID- 26427332
TI - Self-criticism in therapist training: A grounded theory analysis.
AB - OBJECTIVE: The primary objective of this study is to engender an understanding of
how therapists-in-training experience and cope with self-criticism in the context
of their clinical training and therapy experiences. METHOD: In this study,
trainees were interviewed about their experience of self-criticism related to
psychotherapy practice and these interviews were subjected to a grounded theory
analysis generating a core self-critical process. RESULTS: The analysis
highlighted the vulnerability of self-criticism in therapists' training
experiences, especially when they related to balancing the "expert" role while
maintaining authentic interactions with their clients. The results also described
ways in which self-criticism is mitigated by a sense of interpersonal safety and
the provision of clinical freedom and flexibility in therapists' training.
CONCLUSIONS: The implications for future psychotherapy research and clinical
training within clinical training environments are discussed.
PMID- 26427329
TI - Small molecule therapeutics targeting F-box proteins in cancer.
AB - The ubiquitin proteasome system (UPS) plays vital roles in maintaining protein
equilibrium mainly through proteolytic degradation of targeted substrates. The
archetypical SCF ubiquitin E3 ligase complex contains a substrate recognition
subunit F-box protein that recruits substrates to the catalytic ligase core for
its polyubiquitylation and subsequent proteasomal degradation. Several well
characterized F-box proteins have been demonstrated that are tightly linked to
neoplasia. There is mounting information characterizing F-box protein-substrate
interactions with the rationale to develop unique therapeutics for cancer
treatment. Here we review that how F-box proteins function in cancer and
summarize potential small molecule inhibitors for cancer therapy.
PMID- 26427335
TI - Identification of a novel HLA-B*46:01 variant, HLA-B*46:01:20, in a Taiwanese
unrelated hematopoietic stem cell donor.
AB - One nucleotide replacement at residue 528 of HLA-B*46:01:01 results in a new
allele, HLA-B*46:01:20.
PMID- 26427334
TI - A common promoter hypomethylation signature in invasive breast, liver and
prostate cancer cell lines reveals novel targets involved in cancer invasiveness.
AB - Cancer invasion and metastasis is the most morbid aspect of cancer and is
governed by different cellular mechanisms than those driving the deregulated
growth of tumors. We addressed here the question of whether a common DNA
methylation signature of invasion exists in cancer cells from different origins
that differentiates invasive from non-invasive cells. We identified a common DNA
methylation signature consisting of hyper- and hypomethylation and determined the
overlap of differences in DNA methylation with differences in mRNA expression
using expression array analyses. A pathway analysis reveals that the
hypomethylation signature includes some of the major pathways that were
previously implicated in cancer migration and invasion such as TGF beta and ERBB2
triggered pathways. The relevance of these hypomethylation events in human tumors
was validated by identification of the signature in several publicly available
databases of human tumor transcriptomes. We shortlisted novel invasion promoting
candidates and tested the role of four genes in cellular invasiveness from the
list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion.
Importantly these genes are upregulated in human cancer specimens as determined
by immunostaining of human normal and cancer breast, liver and prostate tissue
arrays. Since these genes are activated in cancer they constitute a group of
targets for specific pharmacological inhibitors of cancer invasiveness. SUMMARY:
Our study provides evidence that common DNA hypomethylation signature exists
between cancer cells derived from different tissues, pointing to a common
mechanism of cancer invasiveness in cancer cells from different origins that
could serve as drug targets.
PMID- 26427336
TI - Novel Chiral Bifunctional L-Thiazoline-Thiourea Derivatives: Design and
Application in Enantioselective Michael Reactions.
AB - Several novel chiral bifunctional L-thiazoline-thiourea derivatives were easily
synthesized from commercially available L-cysteine in high yield. These catalysts
were subsequently applied to the enantioselective Michael addition of
acetylacetone to beta-nitrostyrenes. The products with S configuration were
obtained in 98% enantiomeric excess (ee) when the L-thiazoline-thiourea
derivatives were used. A plausible transition state model is proposed to explain
the observed enantioselectivities.
PMID- 26427337
TI - Rare k-mer DNA: Identification of sequence motifs and prediction of CpG island
and promoter.
AB - Empirical analysis on k-mer DNA has been proven as an effective tool in finding
unique patterns in DNA sequences which can lead to the discovery of potential
sequence motifs. In an extensive study of empirical k-mer DNA on hundreds of
organisms, the researchers found unique multi-modal k-mer spectra occur in the
genomes of organisms from the tetrapod clade only which includes all mammals. The
multi-modality is caused by the formation of the two lowest modes where k-mers
under them are referred as the rare k-mers. The suppression of the two lowest
modes (or the rare k-mers) can be attributed to the CG dinucleotide inclusions in
them. Apart from that, the rare k-mers are selectively distributed in certain
genomic features of CpG Island (CGI), promoter, 5' UTR, and exon. We correlated
the rare k-mers with hundreds of annotated features using several bioinformatic
tools, performed further intrinsic rare k-mer analyses within the correlated
features, and modeled the elucidated rare k-mer clustering feature into a
classifier to predict the correlated CGI and promoter features. Our correlation
results show that rare k-mers are highly associated with several annotated
features of CGI, promoter, 5' UTR, and open chromatin regions. Our intrinsic
results show that rare k-mers have several unique topological, compositional, and
clustering properties in CGI and promoter features. Finally, the performances of
our RWC (rare-word clustering) method in predicting the CGI and promoter features
are ranked among the top three, in eight of the CGI and promoter evaluations,
among eight of the benchmarked datasets.
PMID- 26427338
TI - Effect of walking speed on the gait of king penguins: An accelerometric approach.
AB - Little is known about non-human bipedal gaits. This is probably due to the fact
that most large animals are quadrupedal and that non-human bipedal animals are
mostly birds, whose primary form of locomotion is flight. Very little research
has been conducted on penguin pedestrian locomotion with the focus instead on
their associated high energy expenditure. In animals, tri-axial accelerometers
are frequently used to estimate physiological energy cost, as well as to define
the behaviour pattern of a species, or the kinematics of swimming. In this study,
we showed how an accelerometer-based technique could be used to determine the
biomechanical characteristics of pedestrian locomotion. Eight king penguins,
which represent the only family of birds to have an upright bipedal gait, were
trained to walk on a treadmill. The trunk tri-axial accelerations were recorded
while the bird was walking at four different speeds (1.0, 1.2, 1.4 and 1.6km/h),
enabling the amplitude of dynamic body acceleration along the three axes
(amplitude of DBAx, DBAy and DBAz), stride frequency, waddling and leaning
amplitude, as well as the leaning angle to be defined. The magnitude of the
measured variables showed a significant increase with increasing speed, apart
from the backwards angle of lean, which decreased with increasing speed. The
variability of the measured variables also showed a significant increase with
speed apart from the DBAz amplitude, the waddling amplitude, and the leaning
angle, where no significant effect of the walking speed was found. This paper is
the first approach to describe 3D biomechanics with an accelerometer on wild
animals, demonstrating the potential of this technique.
PMID- 26427339
TI - Liver Contrast-Enhanced Ultrasound Improves Detection of Liver Metastases in
Patients with Pancreatic or Periampullary Cancer.
AB - The aim of this study is to provide a diagnostic performance evaluation of
contrast-enhanced ultrasonography (CEUS) in detecting liver metastases in
patients with suspected of pancreatic or periampullary cancer. Computed
tomography (CT) is often insufficient for detection of liver metastases, but
their presence plays a crucial role in the choice of therapy. Eighty-nine
patients with suspected pancreatic or periampullary cancer were included in this
prospective study with retrospective analysis. Patients underwent an abdominal CT
and CEUS. Fifteen patients had liver metastases. The CT sensitivity was 73.3%
(11/15), the specificity 93.2% (69/74), the positive predictive value (PPV) 68.8%
(11/16) and the negative predictive value (NPV) 94.6% (69/73). Based on CEUS, the
sensitivity was 80% (12/15), specificity 98.6% (73/74), PPV 92.3% (12/13) and NPV
96.1% (73/76). CEUS improved characterization of liver lesions in patients with
suspected pancreatic or periampullary cancer compared with CT. CEUS can better
detect benign liver lesions and distinguish false-positive or indeterminate CT
results.
PMID- 26427340
TI - Polypropylene/Polyaniline Nanofiber/Reduced Graphene Oxide Nanocomposite with
Enhanced Electrical, Dielectric, and Ferroelectric Properties for a High Energy
Density Capacitor.
AB - This work demonstrates a ternary nanocomposite system, composed of polypropylene
(PP), redoped PANI (r-PANI) nanofibers, and reduced graphene oxides (RGOs), for
use in a high energy density capacitor. r-PANI nanofibers were fabricated by the
combination methods of chemical oxidation polymerization and secondary doping
processes, resulting in higher conductivity (sigma~156 S cm(-1)) than that of the
primarily doped PANI nanofibers (sigma~16 S cm(-1)). RGO sheets with high
electron mobility and thermal stability can enhance the conductivity of r
PANI/RGO (sigma~220 S cm(-1)) and thermal stability of PP matrix. These findings
could be extended to combine the advantages of r-PANI nanofibers and RGO sheets
for developing an efficient means of preparing PP/r-PANI/RGO nanocomposite. When
the r-PANI/RGO cofillers (10 vol %) were added to PP matrix, the resulting PP/r
PANI/RGO nanocomposite exhibited high dielectric constant (epsilon'~51.8) with
small dielectric loss (epsilon"~9.3*10(-3)). Furthermore, the PP/r-PANI/RGO
nanocomposite was used for an energy-harvesting device, which demonstrated high
energy density (Ue~12.6 J cm(-3)) and breakdown strength (E~5.86*10(3) kV cm(
1)).
PMID- 26427341
TI - Therapeutic education and self-care: Results from the cross-sectional study
Diabetes, Attitudes, Wishes and Needs 2 (DAWN2) in Spain.
AB - INTRODUCTION: Therapeutic education (TE) has been gradually introduced
progressively into diabetes mellitus care programs with the aim of providing
patients and their families or caregivers with the necessary skills for the self
management of the disease. The Diabetes Attitudes, Wishes and Needs 2 (DAWN2)
study helps to clarify what are the unmet needs with regards to self-management
and the TE offer available to patients and their families. The objective of this
paper is to analyse the results of the DAWN2 study regarding self-care habits and
participation in TE activities in Spain. METHODS: The DAWN2 is an observational,
cross-national study. In this paper, an analysis was performed on the Spanish
sample of diabetic patients (502) and family members (123). RESULTS: Patients
report taking their medications as recommended by their doctor an average of 6.4
days/week, and self-monitor their blood glucose an average of 3.4 days/week. The
large majority (86%) of patients with diabetes mellitus type 1, 59% of patients
with diabetes mellitus type 2, and 21% of family members state to have
participated in education activities. CONCLUSIONS: Diabetes educators should
reinforce the messages about the benefits of self-care, particularly for patients
who are in the early stages of the disease. Likewise, access for family members
and people with diabetes mellitus type 2 to TE programs should be improved, and
these programs for diabetic patients and their families should be included in the
services portfolio of health centres.
PMID- 26427342
TI - Chemical contaminants in surficial sediment in Coral and Fish Bays, St. John,
U.S. Virgin Islands.
AB - Land based sources of pollution have the potential to negatively impact coral
reef ecosystems. Many coral systems, including environmentally sensitive marine
protected areas, do not have assessments of their chemical contaminant status
(magnitude and extent). Without a status assessment, it is impossible to measure
change in a system. This study presents surficial sediment data from Coral and
Fish Bays (St. John, US Virgin Islands (USVI)). Portions of these bays are
included in Virgin Islands National Park, and Virgin Islands Coral Reef National
Monument. A suite of analytes (PCBs, PAHs, pesticides, heavy metals, butyltins)
was quantified and compared against other regional data and against previously
published sediment quality guidelines (SQG). Contamination from toxic
contaminants in the system was generally low when compared to other similar
studies and potential toxicity thresholds (SQG). Exceptions to this were copper
and total chlordane which exceeded the Effects Range Low (ERL) sediment quality
guideline, indicating possible sediment toxicity. This assessment will be useful
to coastal managers for tracking environmental change, and ensuring that this
marine protected area remains relatively free from toxic contamination.
PMID- 26427343
TI - Cognitive control during sentence generation.
AB - Sentence generation involves selecting the right words out of multiple co
activated representations for the right utterance positions. This selection
process is hypothesized to involve cognitive control. Previous research has
linked cognitive control during language processing to regions within the frontal
lobe, including the anterior cingulate cortex (ACC) and left ventrolateral
prefrontal cortex (VLPFC). We examined the neural correlates of word and sentence
generation to determine whether these cognitive control regions were activated
more for sentences than words. We also manipulated the phonological overlap
between nouns in the sentence to determine whether cognitive control recruitment
increased under phonological competition. Whole-brain analysis revealed increased
activation in the ACC and bilateral frontal cortex for sentences over words.
Region of interest analysis revealed an effect of phonological competition within
the ACC. Psychophysiological interaction (PPI) analysis further showed that
functional connectivity within a task-maintenance network increased under
phonological competition. These results suggest a role for conflict detection and
monitoring during sentence generation, which is consistent with a theoretical
framework incorporating domain-general cognitive control processes into language
processing.
PMID- 26427344
TI - Effects of Maternal Stress During Pregnancy on Birth Outcome and Stress-related
Hormones.
PMID- 26427346
TI - Stable Co-Catalyst-Free Photocatalytic H2 Evolution From Oxidized Titanium
Nitride Nanopowders.
AB - A simple strategy is used to thermally oxidize TiN nanopowder (~20 nm) to an
anatase phase of a TiO2:Ti(3+):N compound. In contrast to the rutile phase of
such a compound, this photocatalyst provides activity for hydrogen evolution
under AM1.5 conditions, without the use of any noble metal co-catalyst. Moreover
the photocatalyst is active and stable over extended periods of time (tested for
4 months). Importantly, to achieve successful conversion to the active anatase
polymorph, sufficiently small starting particles of TiN are needed. The key
factor for catalysis is the stabilization of the co-catalytically active Ti(3+)
species against oxidation by nitrogen present in the starting material.
PMID- 26427347
TI - Identification of a Lead Candidate in the Search for Carbene-Stabilised
Homoaromatics.
AB - The effect of carbenes as Lewis donor groups on the homoaromaticity of mono- and
bicyclic organic molecules is surveyed. The search for viable carbene-stabilised
homoaromatics resulted in a large amount of rejected candidates as well as nine
promising candidates that are further analysed for their homoaromaticity by using
a number of metrics. Of these, five appeared to show modest homoaromaticity,
whereas another compound showed a level of homoaromaticity comparable with the
homotropylium cation benchmark compound. Isoelectronic analogues and
constitutional isomers of the lead compound were investigated, however, none of
these showed comparable homoaromaticity. The implications of these calculations
on the design of donor-stabilised homoaromatics are discussed.
PMID- 26427345
TI - A cell-free expression and purification process for rapid production of protein
biologics.
AB - Cell-free protein synthesis has emerged as a powerful technology for rapid and
efficient protein production. Cell-free methods are also amenable to automation
and such systems have been extensively used for high-throughput protein
production and screening; however, current fluidic systems are not adequate for
manufacturing protein biopharmaceuticals. In this work, we report on the initial
development of a fluidic process for rapid end-to-end production of recombinant
protein biologics. This process incorporates a bioreactor module that can be used
with eukaryotic or prokaryotic lysates that are programmed for combined
transcription/translation of an engineered DNA template encoding for specific
protein targets. Purification of the cell-free expressed product occurs through a
series of protein separation modules that are configurable for process-specific
isolation of different proteins. Using this approach, we demonstrate production
of two bioactive human protein therapeutics, erythropoietin and granulocyte
macrophage colony-stimulating factor, in yeast and bacterial extracts,
respectively, each within 24 hours. This process is flexible, scalable and
amenable to automation for rapid production at the point-of-need of proteins with
significant pharmaceutical, medical, or biotechnological value.
PMID- 26427348
TI - NHS commissioning in probation in England - on a wing and a prayer.
AB - National guidance in England exhorts Clinical Commissioning Groups [groups of
general practices established to organise delivery of National Health Service
(NHS) care in their local area (CCGs)] to commission healthcare for those living
in the community who are serving non-custodial sentences called 'community
orders'. This includes 'approved premises' - accommodation providing enhanced
supervision for offenders and individuals on bail who may present a high risk of
harm to the public. In this national survey of CCGs in England, we compared the
extent to which healthcare services were commissioned for probationers in 2014
with similar data we collected in 2013. A freedom of information (FOI) request
was sent to all CCGs (n = 212) and Mental Health Trusts (organisations
commissioned to provide health and social care services to individuals with
mental health disorders) (n = 53) in England. Mental Health Trusts were included
as they were known to fund mental health services for probation as part of their
block funding allocations. A small number of basic questions were asked. The
response rate was good with 65% of CCGs (n = 137) and 68% (n = 36) of Mental
Health Trusts responding. The findings show that the proportion of CCGs
commissioning healthcare for probation reduced from 7% to 1%, with 20% of CCGs
stating that funding healthcare for this group was the responsibility of the NHS
England Area Teams. There was also a reduction in the proportion of Mental Health
Trusts funding healthcare for probation but from a much higher baseline, that is
from 70% to 61%. The prevalence of mental health disorders in probation is high,
so it was of concern that only 12% of Mental Health Trusts provided a service to
support approved premises and just 32% provided clinics in probation. The results
are discussed within the context of the NHS reforms and the government's plans in
England to reform probation.
PMID- 26427349
TI - [Effects of satisfaction with leisure time in family carers of elderly
dependents].
AB - AIM: To analyse the relationship between satisfaction with leisure time and
subjective burden, depression and anxiety in caregivers of dependent elderly
relatives. DESIGN: Cross-sectional study. LOCATION: Primary health care
(Andalusia, Spain). PARTICIPANTS: A probabilistic sample of 200 primary
caregivers of dependent elderly relatives. MAIN MEASUREMENTS: Satisfaction with
leisure time, subjective burden, anxiety, depression, and objective burden
(functional ability, cognitive impairment and behavioural problems of the care
recipient, and dedication to caring of the caregiver). RESULTS: Most of the
caregivers were women, daughters of the care recipients, and shared home with
them. An inverse statistical association was found between satisfaction with
leisure time and subjective burden (r=-0.55, 95%CI: -0.45 to -0.64), anxiety (r=
0.30, 95%CI: -0.17 to -0.41) and depression (r=-0.25, 95%CI: -0.11 to -0.37).
These associations remained after controlling for objective burden. CONCLUSIONS:
Satisfaction with leisure time may have a protective effect on subjective burden,
anxiety and depression, regardless of objective burden.
PMID- 26427350
TI - Ginsenoside Rg3 induces FUT4-mediated apoptosis in H. pylori CagA-treated gastric
cancer cells by regulating SP1 and HSF1 expressions.
AB - Helicobacter pylori (H. pylori) cytotoxin associated antigen A (CagA) plays a
significant role in the development of gastric cancer. Ginsenoside Rg3 is a
herbal medicine which inhibits cell proliferation and induces apoptosis in
various cancer cells. Fucosylation plays important roles in cancer biology as
increased fucosylation levels of glycoproteins and glycolipids have been reported
in many cancers. Fucosyltransferase IV (FUT4) is an essential enzyme, catalyzes
the synthesis of LewisY oligosaccharides and is regulated by specificity protein
1 (SP1) and heat shock factor protein 1 (HSF1) transcription factors. Herein, we
studied the mechanism action of Rg3 apoptosis induction in gastric cancer cells.
We treated the gastric cancer cells with CagA followed by Rg3, and analyzed their
ability to induce apoptosis by evaluating the role of FUT4 as well as SP1 and
HSF1 expressions by Western blot, flow cytometry and ELISA. We found that Rg3
significantly induced apoptosis in CagA treated gastric cancer cells, as
evidenced by nuclear staining of 4-6-diamidino-2-phenylindole (DAPI) and Annexin
V/PI double-labeling. In addition, Rg3 significantly increased the expression of
pro-apoptotic proteins and triggered the activation of caspase-3, -8, and -9 and
PARP. Moreover, Rg3-induced apoptotic mechanisms indicated that Rg3 inhibited
FUT4 expression through SP1 upregulation and HSF1 downregulation. Hence, Rg3
therapy is an effective strategy for gastric cancer treatment. Furthermore SP1
and HSF1 may serve as potential diagnostic and therapeutic targets for gastric
cancer.
PMID- 26427351
TI - Functional structure and physiological functions of mammalian wild-type HSP60.
AB - The Chaperonins comprise a family of molecular chaperones having a double-ring
structure and similar sequence homology. These proteins play an essential role in
biological reactions that mediate the folding of newly synthesized polypeptides
and partially denatured proteins. In the prokaryotic group I chaperonins,
structural and reaction cycle analyses of GroEL and its co-chaperone GroES have
been performed in detail. While in eukaryotes, there have been limited reports
analyzing the group I chaperonin HSP60 and its co-chaperone HSP10. In the present
study, we purified the wild type HSP60 from porcine liver and investigated the
interaction between HSP60 and HSP10, including conformation and physiological
relationships. Based on the results of transmission electron microscopy, native
PAGE, and gel filtration column chromatography, the wild type HSP60 displayed a
heptameric single-ring structure in the absence of ATP. In contrast, HSP60 formed
mainly a "football-type" complex with HSP10 in the presence of ATP and mediated
the refolding of denatured substrate protein. The functional conformation cycle
of the purified mammalian HSP60 is distinct from the cycle of the prokaryotic
GroEL/GroES chaperonin.
PMID- 26427352
TI - Glutathione modifies the oxidation products of 2'-deoxyguanosine by singlet
molecular oxygen.
AB - The oxidation of the free nucleoside 2'-deoxyguanosine (dGuo) by singlet
molecular oxygen ((1)O2) has been studied over the three last decades due to the
major role of DNA oxidation products in process such as ageing, mutation and
carcinogenesis. In the present work we investigated the dGuo oxidation by (1)O2
in the presence of the important low molecular antioxidant, glutathione, in its
reduced (GSH) and oxidized (GSSG) forms. There were applied different conditions
of concentration, pH, time of incubation, and the use of a [(18)O]-labeled
thermolabile endoperoxide naphthalene derivative as a source of [(18)O]-labeled
(1)O2. Data was obtained through high performance liquid chromatography (HPLC)
and HPLC coupled to micrOTOF Q-II analysis of the main oxidation products: the
diastereomers of spiroiminodihydantoin-2'-deoxyribonucleosides (dSp) and 8-oxo
7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). An intriguing result was that 8
oxodGuo levels increased by 100 fold when dGuo was oxidized by (1)O2 in the
presence of GSH and by 2 fold in the presence of GSSG, while dSp levels dropped
to zero for both conditions. All data from dGuo, 8-oxodGuo and dSp quantification
together with the analysis of residual GSH/GSSG content in each sample strongly
suggest that glutathione modifies the mechanism of dGuo oxidation by (1)O2 by
disfavoring the pathway of dSp formation.
PMID- 26427353
TI - Early response as shown by enhancement of transglutaminase 1 expression after
cisplatin-induced acute kidney injury.
AB - Acute kidney injury (AKI) is caused by drugs and other stimuli, which limits the
use of several therapeutic approaches. The AKI mouse model generated by
intraperitoneal administration with cisplatin, one of the most widely used anti
cancer drugs, is generally applied to study on this disease. Transglutaminases
are posttranslational modifying enzymes that catalyze irreversible cross-linking
reactions between proteins in several biological events such as skin formation
and blood coagulation. In this study, we found an increase in the expression
level of transglutaminase (TG1) in the kidney of mice which had been injected
with cisplatin and underwent progressive nephrotoxicity. Before the appearance of
the tentative symptoms of renal failure, which is apparent by morphological
damage in the kidney and increases in blood creatinine levels, both the
expression level and activity of TG1 rapidly increased mainly at the proximal
tubule. On the other hand, the protein expression level of another major isozyme
(TG2) remained mostly unaltered. This investigation will provide a possible basal
level biomarker and also information on progression of renal failure from the
aspect of the protein-modifying enzyme, transglutaminase.
PMID- 26427354
TI - Expression, regulation and functional assessment of the 80 amino acid Small
Adipocyte Factor 1 (Smaf1) protein in adipocytes.
AB - The gene for Small Adipocyte Factor 1, Smaf1 (also known as adipogenin, ADIG),
encodes a ~600 base transcript that is highly upregulated during 3T3-L1 in vitro
adipogenesis and markedly enriched in adipose tissues. Based on the lack of an
obvious open reading frame in the Smaf1 transcript, it is not known if the Smaf1
gene is protein coding or non-coding RNA. Using a peptide from a putative open
reading frame of Smaf1 as antigen, we generated antibodies for western analysis.
Our studies prove that Smaf1 encodes an adipose-enriched protein which in western
blot analysis migrates at ~10 kDa. Rapid induction of Smaf1 protein occurs during
in vitro adipogenesis and its expression in 3T3-L1 adipocytes is positively
regulated by insulin and glucose. Moreover, siRNA studies reveal that expression
of Smaf1 in adipocytes is wholly dependent on PPARgamma. On the other hand, use
of siRNA for Smaf1 to nearly abolish its protein expression in adipocytes
revealed that Smaf1 does not have a major role in adipocyte triglyceride
accumulation, lipolysis or insulin-stimulated pAkt induction. However,
immunolocalization studies using HA-tagged Smaf1 reveal enrichment at adipocyte
lipid droplets. Together our findings show that Smaf1 is a novel small protein
endogenous to adipocytes and that Smaf1 expression is closely tied to PPARgamma
mediated signals and the adipocyte phenotype.
PMID- 26427355
TI - China and the United States--Global partners, competitors and collaborators in
nanotechnology development.
AB - USA and China are two leading countries engaged in nanotechnology research and
development. They compete with each other for fruits in this innovative area in a
parallel and compatible manner. Understanding the status and developmental
prospects of nanotechnology in USA and China is important for policy-makers to
decide nanotechnology priorities and funding, and to explore new ways for global
cooperation on key issues. We here present the nanoscience and nanomedicine
research and the related productivity measured by publications, and patent
applications, governmental funding, policies and regulations, institutional
translational research, industrial and enterprise growth in nanotechnology
related fields across China and USA. The comparison reveals some marked
asymmetries of nanotechnology development in China and USA, which may be helpful
for future directions to strengthen nanotechnology collaboration for both
countries, and for the world as a whole.
PMID- 26427356
TI - Shape regulated anticancer activities and systematic toxicities of drug
nanocrystals in vivo.
AB - In this paper, shape regulated anticancer activities as well as systematic
toxicities of hydroxycamptothecin nanorods and nanoparticles (HCPT NRs and NPs)
were systematically studied. In vitro and in vivo therapeutic efficacies were
evaluated in cancer cells and tumor-bearing mice, indicating that NRs possessed
superior antitumor efficacy over NPs at the equivalent dose, while systematic
toxicity of the differently shaped nanodrugs assessed in healthy mice, including
the maximum tolerated dose, blood analysis and histology examinations and so on,
suggested that the NRs also caused higher toxicities than NPs, and also had a
long-term toxicity. These results imply that the balance between anticancer
efficiency and systematic toxicity of drug nanocrystals should be fully
considered in practice, which will provide new concept in the future design of
drug nanocrystals for cancer therapy. From the Clinical Editor: Advances in
nanotechnology have enabled the design of novel nanosized drugs for the treatment
of cancer. One of the interesting findings thus far is the different biological
effects seen with different shaped nanoparticles. In this article, the authors
investigated and compared the anticancer activities of hydroxycamptothecin
nanorods and nanoparticles. The experimental data would provide a better
understanding for future drug design.
PMID- 26427357
TI - A commentary on "Involvement of activating ERK1/2 trough G protein coupled
receptor 30 and estrogen receptor alpha/beta in low doses of bisphenol A
promoting growth of Sertoli TM4 cells".
PMID- 26427358
TI - Cancer surgery: a vital specialty to prevent premature death.
PMID- 26427359
TI - Primacy of surgery in cancer care: a global situation.
PMID- 26427360
TI - Cancer surgery: an Indian-Asian perspective.
PMID- 26427361
TI - Cancer surgery in Africa: if all you have is a hammer....
PMID- 26427362
TI - The surgeon's role in childhood cancer worldwide.
PMID- 26427363
TI - Global cancer surgery: delivering safe, affordable, and timely cancer surgery.
AB - Surgery is essential for global cancer care in all resource settings. Of the 15.2
million new cases of cancer in 2015, over 80% of cases will need surgery, some
several times. By 2030, we estimate that annually 45 million surgical procedures
will be needed worldwide. Yet, less than 25% of patients with cancer worldwide
actually get safe, affordable, or timely surgery. This Commission on global
cancer surgery, building on Global Surgery 2030, has examined the state of global
cancer surgery through an analysis of the burden of surgical disease and breadth
of cancer surgery, economics and financing, factors for strengthening surgical
systems for cancer with multiple-country studies, the research agenda, and the
political factors that frame policy making in this area. We found wide equity and
economic gaps in global cancer surgery. Many patients throughout the world do not
have access to cancer surgery, and the failure to train more cancer surgeons and
strengthen systems could result in as much as US $6.2 trillion in lost cumulative
gross domestic product by 2030. Many of the key adjunct treatment modalities for
cancer surgery--e.g., pathology and imaging--are also inadequate. Our analysis
identified substantial issues, but also highlights solutions and innovations.
Issues of access, a paucity of investment in public surgical systems, low
investment in research, and training and education gaps are remarkably
widespread. Solutions include better regulated public systems, international
partnerships, super-centralisation of surgical services, novel surgical clinical
trials, and new approaches to improve quality and scale up cancer surgical
systems through education and training. Our key messages are directed at many
global stakeholders, but the central message is that to deliver safe, affordable,
and timely cancer surgery to all, surgery must be at the heart of global and
national cancer control planning.
PMID- 26427364
TI - Anal Pap Screening for HIV-infected Men Who Have Sex With Men: Practice
Improvement.
AB - HIV-infected men who have sex with men (MSM) have the highest rates of anal
dysplasia and anal cancer when compared to HIV-uninfected MSM and when compared
to HIV-infected heterosexual men and women. Despite significantly increasing
rates of anal dysplasia and anal cancer in HIV-infected MSM, in many settings, no
standard protocol is in place to screen for anal dysplasia in this high-risk
group. A practice improvement project was conducted at a primary care health
center to educate the HIV health care team about anal Pap screening in an effort
to increase provider knowledge and rates of anal Pap screening performed as part
of primary comprehensive care for HIV-infected MSM. Increased health care
provider knowledge of anal Pap screening within this setting resulted in
increased anal Pap screening for HIV-infected MSM. Routine screening leads to
improved surveillance and treatment of precancerous lesions, decreasing morbidity
and mortality in HIV-infected MSM.
PMID- 26427365
TI - Diagnostic accuracy of the rapid urine lipoarabinomannan test for pulmonary
tuberculosis among HIV-infected adults in Ghana-findings from the DETECT HIV-TB
study.
AB - BACKGROUND: Rapid diagnostic tests are urgently needed to mitigate HIV-associated
tuberculosis (TB) mortality. We evaluated diagnostic accuracy of the rapid urine
lipoarabinomannan (LAM) test for pulmonary TB and assessed the effect of a two
sample strategy. METHODS: HIV-infected adults eligible for antiretroviral therapy
were prospectively enrolled from Korle-Bu Teaching Hospital in Ghana and followed
for minimum 6 months. We applied the LAM test on urine collected as a spot and
early morning sample. Diagnostic accuracy was analysed for a microbiological TB
reference standard based on sputum culture and Gene Xpert MTB/RIF results and for
a composite reference standard including clinical follow-up data. Performance of
sputum smear microscopy was included for comparison. RESULTS: Of 469 patients
investigated for TB, the LAM test correctly identified 24/55 (44 %) of
microbiologically confirmed TB cases. Sensitivity of the LAM test was positively
associated with hospitalisation (67 %), Modified Early Warning Score > 4 (57 %)
and subsequent death (71 %). LAM test specificity was 95 % increasing to 98 % for
the composite reference standard. A two-sample LAM test strategy did not improve
test performance. Using concentrated sputum for Ziehl-Neelsen and fluorescence
microscopy in combination yielded a sensitivity of 31/55 (56 %) that increased to
35/55 (64 %) when the LAM test was added. Surprisingly, nontuberculous
mycobacteria were cultured in 34/469 (7 %) and associated with a positive LAM
test (p = 0.008). CONCLUSIONS: LAM test sensitivity was highest in patients with
poor prognosis and subsequent death and did not increase with a two-sample
strategy. A rigorous sputum microscopy strategy had superior sensitivity, but the
simplicity of the LAM test holds operational possibilities as a TB screening
method among severely sick patients.
PMID- 26427366
TI - A Comparison of transgenic and wild type soybean seeds: analysis of transcriptome
profiles using RNA-Seq.
AB - BACKGROUND: Soybean (Glycine max) has been bred for thousands of years to produce
seeds rich in protein for human and animal consumption, making them an appealing
bioreactor for producing valuable recombinant proteins at high levels. However,
the effects of expressing recombinant protein at high levels on bean physiology
are not well understood. To address this, we investigated whether gene expression
within transgenic soybean seed tissue is altered when large amounts of
recombinant proteins are being produced and stored exclusively in the seeds. We
used RNA-Seq to survey gene expression in three transgenic soybean lines
expressing recombinant protein at levels representing up to 1.61 % of total
protein in seed tissues. The three lines included: ST77, expressing human
thyroglobulin protein (hTG), ST111, expressing human myelin basic protein (hMBP),
and 764, expressing a mutant, nontoxic form of a staphylococcal subunit vaccine
protein (mSEB). All lines selected for analysis were homozygous and contained a
single copy of the transgene. METHODS: Each transgenic soybean seed was screened
for transgene presence and recombinant protein expression via PCR and western
blotting. Whole seed mRNA was extracted and cDNA libraries constructed for
Illumina sequencing. Following alignment to the soybean reference genome,
differential gene expression analysis was conducted using edgeR and cufflinks.
Functional analysis of differentially expressed genes was carried out using the
gene ontology analysis tool AgriGO. RESULTS: The transcriptomes of nine seeds
from each transgenic line were sequenced and compared with wild type seeds.
Native soybean gene expression was significantly altered in line 764 (mSEB) with
more than 3000 genes being upregulated or downregulated. ST77 (hTG) and ST111
(hMBP) had significantly less differences with 52 and 307 differentially
expressed genes respectively. Gene ontology enrichment analysis found that the
upregulated genes in the 764 line were annotated with functions related to
endopeptidase inhibitors and protein synthesis, but suppressed expression of
genes annotated to the nuclear pore and to protein transport. No significant gene
ontology terms were detected in ST77, and only a few genes involved in
photosynthesis and thylakoid functions were downregulated in ST111. Despite these
differences, transgenic plants and seeds appeared phenotypically similar to non
transgenic controls. There was no correlation between recombinant protein
expression level and the quantity of differentially expressed genes detected.
CONCLUSIONS: Measurable unscripted gene expression changes were detected in the
seed transcriptomes of all three transgenic soybean lines analyzed, with line 764
being substantially altered. Differences detected at the transcript level may be
due to T-DNA insert locations, random mutations following transformation or
direct effects of the recombinant protein itself, or a combination of these. The
physiological consequences of such changes remain unknown.
PMID- 26427367
TI - Caffeine differentially alters cortical hemodynamic activity during working
memory: a near infrared spectroscopy study.
AB - BACKGROUND: Caffeine is a widely used stimulant with potentially beneficial
effects on cognition as well as vasoconstrictive properties. In functional
magnetic imaging research, caffeine has gained attention as a potential enhancer
of the blood oxygenation level-dependent (BOLD) response. In order to clarify
changes of oxy- and deoxyhemoglobin (HbO and HbR) induced by caffeine during a
cognitive task, we investigated a working memory (WM) paradigm (visual 2-back)
using near-infrared spectroscopy (NIRS). RESULTS: Behaviorally, caffeine had no
effect on the WM performance but influenced reaction times in the 0-back
condition. NIRS data demonstrate caffeine-dependent alterations of the course of
the hemodynamic response. The intake of 200 mg caffeine caused a significant
decrease of the HbO response between 20 and 40 s after the onset of a 2-back task
in the bilateral inferior frontal cortex (IFC). In parallel, the HbR response of
the left IFC was significantly increased due to caffeine intake. CONCLUSIONS: In
line with previous results, we did not detect an effect of caffeine on most
aspects of behavior. Effects of caffeine on brain vasculature were detected as
general reduction of HbO. Neuronal effects of caffeine are reflected in an
increased concentration of HbR in the left hemisphere when performing a verbal
memory task and suggest influences on metabolism.
PMID- 26427368
TI - Clinical impact of diabetes mellitus in patients undergoing transcatheter aortic
valve replacement.
AB - BACKGROUND: Diabetes mellitus (DM) and aortic stenosis (AS) are frequent findings
in the elderly population. Data regarding the influence of DM on the outcomes of
patients undergoing transcatheter aortic valve replacement (TAVR) due to AS are
limited. The aim of this study was to examine the impact of DM on TAVR outcomes.
METHODS: We investigated 443 patients with severe AS undergoing TAVR. Subjects
were divided into insulin-dependent diabetic mellitus (IDDM) patients (N = 44),
non-dependent insulin diabetic mellitus (NIDDM) patients (N = 114) and non
diabetics (N = 285) of whom 31 (74%), 86 (79%) and 209 (76%) respectively had
trans-femoral TAVR. Peri-procedural complications and outcomes were recorded
according to the Valve Academic Research Consortium-2 criteria. RESULTS: Patients
with IDDM as well as NIDDM demonstrated similar complication rates compared with
non-diabetic patients, except for acute kidney injury (AKI) grade 3 [4 (2%) and 3
(3%) vs. 1 (0.4%) respectively, p = 0.032]. Kaplan-Meier survival analysis showed
that DM, regardless of the type of treatment, was not associated with increased 2
years mortality (Log-rank p value 0.44). Multivariate cox regression analysis
adjusted for age, gender, coronary artery disease, DM, AKI3, hypertension,
chronic renal failure and peripheral vascular disease found that AKI3 was
associated with increased risk of 2 years mortality [HR = 7.35, 95% CI 2.16
25.07, p = 0.001] whereas female gender was found as a protective factor [HR =
0.47, 95% CI 0.28-0.8, p = 0.005], and DM was not associated with increased risk.
CONCLUSIONS: Following TAVR, DM patients seem to have similar peri-procedural and
mid-term outcomes compared with patients without DM, while IDDM patients seem to
suffer greater incidence of AKI. Further research in larger cohorts of patients
is needed to validate our results.
PMID- 26427369
TI - In a context of time: the impact of delay and exposure time on the emergence of
memory context effects.
AB - Research on context-mediated facilitation of recognition memory distinguishes
between the effects of reinstating the exact same context previously associated
with a target and a context that is familiar but not directly associated with the
target. As both effects are difficult to produce reliably in recognition
experiments, attention has turned to measures that may explain inconsistencies,
such as the extent to which instructions encourage association between targets
and contexts. The aim of the current study was to examine the distinctive and
interactive effects of three factors that may lead to variability in context
effects (CEs), namely type of instructions given at learning, delay between
learning and test, and exposure time for targets and contexts at learning. Using
a comprehensive paradigm developed by Vakil and colleagues, with photographs of
faces serving as target and context stimuli, both exposure time and delay were
shown to be associated with the occurrence of CEs and appeared to interact with
one another in determining the nature of these effects. Unlike several previous
studies, false alarms did not increase when foils were presented with familiar
contexts. Also unexpectedly, the instruction manipulation did not appear to
strengthen target-context binding. It may instead have increased attention to
contexts at the expense of targets, as suggested by the finding that direct
memory for context improved under associative instruction conditions. Overall,
the study demonstrates the importance of understanding and controlling various
factors that may potentially influence the emergence of both reinstatement and
familiarity-based CEs, among them exposure time and learning-to-test delay.
PMID- 26427370
TI - What happens when pharmaceuticals meet colloids.
AB - Pharmaceuticals (PCs) have been widely detected in natural environment due to
agricultural application of reclaimed water, sludge and animal wastes. Their
potential risks to various ecosystems and even to human health have caused great
concern; however, little was known about their environmental behaviors. Colloids
(such as clays, metal oxides, and particulate organics) are kind of substances
that are active and widespread in the environment. When PCs meet colloids, their
interaction may influence the fate, transport, and toxicity of PCs. This review
summarizes the progress of studies on the role of colloids in mediating the
environmental behaviors of PCs. Synthesized results showed that colloids can
adsorb PCs mainly through ion exchange, complexation and non-electrostatic
interactions. During this process the structure of colloids and the stability of
PCs may be changed. The adsorbed PCs may have higher risks to induce antibiotic
resistance; besides, their transport may also be altered considering they have
great chance to move with colloids. Solution conditions (such as pH, ionic
strength, and cations) could influence these interactions between PCs and
colloids, as they can change the forms of PCs and alter the primary forces
between PCs and colloids in the solution. It could be concluded that PCs in
natural soils could bind with colloids and then co-transport during the processes
of irrigation, leaching, and erosion. Therefore, colloid-PC interactions need to
be understood for risk assessment of PCs and the best management practices of
various ecosystems (such as agricultural and wetland systems).
PMID- 26427371
TI - Biological efficacy and toxic effect of emergency water disinfection process
based on advanced oxidation technology.
AB - An innovative and removable water treatment system consisted of strong electric
field discharge and hydrodynamic cavitation based on advanced oxidation
technologies was developed for reactive free radicals producing and waterborne
pathogens eliminating in the present study. The biological efficacy and toxic
effects of this advanced oxidation system were evaluated during water
disinfection treatments. Bench tests were carried out with synthetic microbial
contaminated water, as well as source water in rainy season from a reservoir of
Dalian city (Liaoning Province, China). Results showed that high inactivation
efficiency of Escherichia coli (>5 log) could be obtained for synthetic
contaminated water at a low concentration (0.5-0.7 mg L(-1)) of total oxidants in
3-10 s. The numbers of wild total bacteria (108 * 10(3) CFU mL(-1)) and total
coliforms (260 * 10(2) MPN 100 mL(-1)) in source water greatly reduced to 50 and
0 CFU mL(-1) respectively after treated by the advanced oxidation system, which
meet the microbiological standards of drinking water, and especially that the
inactivation efficiency of total coliforms could reach 100%. Meanwhile, source
water qualities were greatly improved during the disinfection processes. The
values of UV254 in particular were significantly reduced (60-80%) by reactive
free radicals. Moreover, the concentrations of possible disinfection by-products
(formaldehyde and bromide) in treated water were lower than detection limits,
indicating that there was no harmful effect on water after the treatments. These
investigations are helpful for the ecotoxicological studies of advanced oxidation
system in the treatments of chemical polluted water or waste water. The findings
of this work suggest that the developed water treatment system is ideal in the
acute phases of emergencies, which also could offer additional advantages over a
wide range of applications in water pollution control.
PMID- 26427373
TI - Cost-Effectiveness in Hepatic Lobectomy: the Effect of Case Volume on Mortality,
Readmission, and Cost of Care.
AB - OBJECTIVE(S): Higher-volume centers demonstrate better perioperative outcomes for
complex surgical interventions, though resource utilization implications of this
hospital-level variation are unclear. We hypothesized that for hepatic lobectomy,
higher operative volume correlates with better outcomes and lower costs. METHODS:
From 2009 to 2011, 4163 patients undergoing hepatic lobectomy were identified
from the University HealthSystems Consortium database. Univariate, multivariate
logistic regression, and decision analytic models were constructed to identify
differences in hospital utilization and cost. Cost included both index and
readmission hospitalizations, when applicable. RESULTS: The annual number of
hepatic lobectomies performed by the institutions within the study ranged from 1
to 86. The median age of the 4163 patients was 58 years with a roughly equal
gender split (M/F 49 %:51 %) and a racial breakdown which reflected that of the
general US population. For all patients, the overall perioperative mortality rate
was 2.3 % and the 30-day readmission rate was 13.4 %. Hospitals performing >30
hepatic lobectomies per year had significantly lower mortality and readmission
rates than those hospitals performing <=15 lobectomies annually (both p < 0.05).
On multivariate analysis, higher severity of illness (odd ratio (OR) 2.13, 95 %
confidence interval (CI) [1.48-3.07], p < 0.001), discharge to rehab (OR 1.84,
[1.28-2.64], p < 0.001), home with home health care (OR 1.38, [1.08-1.76], p =
0.01), and surgery at a low-volume hospital (OR 1.49, [1.18-1.88], p < 0.001)
were significant predictors of readmission. Conversely, surgical intervention at
high-volume centers was associated with decreased risk of readmission (OR 0.67,
[0.53-0.85], p < 0.001). When both index and readmission costs were considered,
per-patient cost at low-volume centers was 21.9 % higher than at high-volume
centers ($19,669 vs. $16,137). Sensitivity analyses adjusting for perioperative
mortality and readmission at all centers did not significantly change the
analysis. CONCLUSIONS: These data, for the first time, demonstrate that hospital
volume in hepatic lobectomy is an important, modifiable risk factor for
readmission and cost. To optimize resource utilization, patients undergoing
complex hepatic surgery should be directed to higher-volume surgical
institutions.
PMID- 26427372
TI - The role of B-1 cells in inflammation.
AB - B-1 lymphocytes exhibit unique phenotypic, ontogenic, and functional
characteristics that differ from the conventional B-2 cells. B-1 cells
spontaneously secrete germline-like, repertoire-skewed polyreactive natural
antibody, which acts as a first line of defense by neutralizing a wide range of
pathogens before launching of the adaptive immune response. Immunomodulatory
molecules such as interleukin-10, adenosine, granulocyte-macrophage colony
stimulating factor, interleukin-3, and interleukin-35 are also produced by B-1
cells in the presence or absence of stimulation, which regulate acute and chronic
inflammatory diseases. Considerable progress has been made during the past three
decades since the discovery of B-1 cells, which has improved not only our
understanding of their phenotypic and ontogenic uniqueness but also their role in
various inflammatory diseases including influenza, pneumonia, sepsis,
atherosclerosis, inflammatory bowel disease, autoimmunity, obesity and diabetes
mellitus. Recent identification of human B-1 cells widens the scope of this
field, leading to novel innovations that can be implemented from bench to
bedside. Among the vast number of studies on B-1 cells, we have carried out a
literature review highlighting current trends in the study of B-1 cell
involvement during inflammation, which may result in a paradigm shift toward
sustainable therapeutics in various inflammatory diseases.
PMID- 26427374
TI - A Tale of Two Cities: Reconsidering Adjuvant Radiation in Pancreatic Cancer Care.
AB - Adjuvant chemotherapy plays a critical role in the treatment of resected
pancreatic cancer patients. However, the role of adjuvant radiation remains
controversial. This study compares survival between resected pancreatic cancer
patients who received adjuvant radiation and no adjuvant radiation. Medical
records of patients with pancreatic ductal adenocarcinoma who underwent surgical
resection from January 2003 through 2013 at medical centers in Boston and Leiden
were retrospectively reviewed. Propensity score matching was used to correct for
potential selection bias in the allocation of adjuvant chemoradiation versus
chemotherapy alone. Three hundred fifty total patients were identified, of whom
138 (39.4%) received adjuvant radiation. On pathological staging, 245 (70.0%) had
positive lymph nodes, and these patients gained a significant survival benefit
from adjuvant radiation (hazard ratio (HR) 0.74; 95% confidence interval (CI)
0.56-0.99) in the complete cohort. After propensity score matching, adjuvant
radiation lost its prognostic significance in the complete cohort. However, after
matching, patients who survived longer than 12 months and had positive lymph
nodes (n = 108) demonstrated a significant (log-rank p = 0.04) survival benefit
from adjuvant radiation. This study, while non-randomized, suggests that adjuvant
radiation may be associated with a survival benefit for resected pancreatic
cancer patients in specific situations.
PMID- 26427376
TI - Low Non-structured Antiretroviral Therapy Interruptions in HIV-Infected Persons
Who Inject Drugs Receiving Multidisciplinary Comprehensive HIV Care at an
Outpatient Drug Abuse Treatment Center.
AB - Continuous HIV treatment is necessary to ensure successful combined
antiretroviral therapy (cART). The aim of this study was to evaluate the
incidence of patient-initiated non-structured treatment interruptions in HIV
infected persons who inject drugs and who received a multidisciplinary
comprehensive program, including medical HIV care, drug-dependence treatment and
psychosocial support, at a drug outpatient addiction center. Non-structured
treatment interruptions were defined as >=30 consecutive days off cART without
medical indication. During a median follow-up of 53.8 months, 37/132 (28 %)
patients experienced the first non-structured treatment interruptions. The
cumulative probability of cART interruption at 5 years was 31.2 % (95 % CI 22.4
40.0). Current drug use injection >=1/day (HR 14.77; 95 % CI 5.90-36.96) and cART
naive patients (HR 0.35, 95 % CI 0.14-0.93) were predictive factors for non
structured treatment interruptions. HIV care provided at a drug addiction center
is a useful strategy to sustain continuous cART, however, drug abstinence is
essential for the long-term maintenance of cART.
PMID- 26427375
TI - Inferring synthetic lethal interactions from mutual exclusivity of genetic events
in cancer.
AB - BACKGROUND: Synthetic lethality (SL) refers to the genetic interaction between
two or more genes where only their co-alteration (e.g. by mutations,
amplifications or deletions) results in cell death. In recent years, SL has
emerged as an attractive therapeutic strategy against cancer: by targeting the SL
partners of altered genes in cancer cells, these cells can be selectively killed
while sparing the normal cells. Consequently, a number of studies have attempted
prediction of SL interactions in human, a majority by extrapolating SL
interactions inferred through large-scale screens in model organisms. However,
these predicted SL interactions either do not hold in human cells or do not
include genes that are (frequently) altered in human cancers, and are therefore
not attractive in the context of cancer therapy. RESULTS: Here, we develop a
computational approach to infer SL interactions directly from frequently altered
genes in human cancers. It is based on the observation that pairs of genes that
are altered in a (significantly) mutually exclusive manner in cancers are likely
to constitute lethal combinations. Using genomic copy-number and gene-expression
data from four cancers, breast, prostate, ovarian and uterine (total 3980
samples) from The Cancer Genome Atlas, we identify 718 genes that are frequently
amplified or upregulated, and are likely to be synthetic lethal with six key DNA
damage response (DDR) genes in these cancers. By comparing with published data on
gene essentiality (~16000 genes) from ten DDR-deficient cancer cell lines, we
show that our identified genes are enriched among the top quartile of essential
genes in these cell lines, implying that our inferred genes are highly likely to
be (synthetic) lethal upon knockdown in these cell lines. Among the inferred
targets are tousled-like kinase 2 (TLK2) and the deubiquitinating enzyme
ubiquitin-specific-processing protease 7 (USP7) whose overexpression correlates
with poor survival in cancers. CONCLUSION: Mutual exclusivity between frequently
occurring genetic events identifies synthetic lethal combinations in cancers.
These identified genes are essential in cell lines, and are potential candidates
for targeted cancer therapy. Availability: http://bioinformatics.org.au/tools
data/underMutExSL
PMID- 26427377
TI - The consequences of the economic crisis in radiology.
AB - The effects of the economic crisis have led to complex problems in radiology. The
crisis has led to a reduction in the turnover of imaging equipment. This reflects
on the quantity and quality of output, an aspect which is worsened by the
contraction of the radiology market, late payments on supplies, and competitive
procurement of medical goods centralized on a regional or national level. Many
local and national institutions have operated with significant reductions of
reimbursement for procedures, forcing a reorganization of facilities, manpower,
and equipment. The reduction in operating margins of the industry has resulted in
a reduction of invested capital for projects of industrial R&D and direct or
indirect sponsorship. The quality of care will be affected with less comfortable
conditions, reduction of local availability of radiologists, and failure to
invest in lower dose equipment to control population medical radiation exposure.
The crisis resulted in a reduction in the number of graduates in medicine and
scholarships for specialization induced by linear cuts will result in a drastic
reduction of radiological specialists. This will favour the development of
teleradiology services, with the risk of accelerating the demedicalisation of
radiology departments, and isolation of the professionals. MAIN MESSAGES: * The
economic crisis has led to reduction in the turnover of imaging equipment. * The
economic crisis has led to reductions of reimbursement for procedures. * The
economic crisis has led to reductions in operating margins of the industry. * The
economic crisis has led to contraction of quantity and quality of output. * The
economic crisis resulted in demedicalisation of radiology departments and
isolation of professionals.
PMID- 26427378
TI - Complete genome sequence of the siphoviral bacteriophage Betaphi-R3177, which
lyses an OXA-66-producing carbapenem-resistant Acinetobacter baumannii isolate.
AB - In recent years, antimicrobial resistance has become a major medical threat
worldwide. Among these threats, the rapid increase in carbapenem-resistant
Acinetobacter baumannii (CRAB) is a particularly challenging global issue in the
health care setting. In this study, a novel lytic A. baumannii phage, Betaphi
R3177, infecting carbapenem-resistant A. baumannii strains was isolated from
sewage samples at a hospital. The morphology of the phage as assessed by
transmission electron microscopy (TEM) indicated that it belongs to the family
Siphoviridae within the order Caudovirales. It has a linear double-stranded DNA
genome of 47,575 bp with a G+C content of 39.83%. Eighty open reading frames
(ORFs) were predicted; however, only 14 ORFs were annotated as encoding
functional proteins, while most of the ORFs encoded hypothetical proteins. Among
the total ORFs of the phage genome, no toxin-related genes were detected. A
bioinformatics analysis showed that the whole genome sequence of phage Betaphi
R3177 exhibited 62% sequence similarity to that of Acinetobacter phage Betaphi
B1252, but there was no homology seen with other phages. Physiological
characteristics, such as one-step growth properties, pH and temperature
stability, and host cell lysis activity showed this phage has high stability and
lytic activity against host bacteria and therefore has potential applicability as
an antibacterial agent to control pathogens in the hospital environment.
PMID- 26427379
TI - Complete nucleotide sequences of two new begomoviruses infecting the wild
malvaceous plant Melochia sp. in Brazil.
AB - Wild malvaceous plants are hosts for a large number of begomoviruses (genus
Begomovirus, family Geminiviridae) in both the Old World and the New World. Here,
we report the complete genome sequences of two new begomoviruses from Melochia
sp. plants from Brazil. The cloned bipartite genomes, composed of DNA-A and DNA
B, showed the typical organization of the New World begomoviruses but they were
distantly related to the genomes of other begomoviruses. We propose the names
Melochia mosaic virus and Melochia yellow mosaic virus for these begomoviruses.
PMID- 26427380
TI - Comparative analysis of transcriptional profiles of retinoic-acid-induced gene I
like receptors and interferons in seven tissues from ducks infected with avian
Tembusu virus.
AB - Avian Tembusu virus (ATV), an emerging virus that mainly infects laying and
breeding ducks in China, has caused severe economic loss in duck industry.
However, there have been no reports about host innate immune responses during ATV
infection and its correlation with clinical signs or pathology. To identify the
roles of these immune factors in the innate host response to ATV infection,
quantitative real-time PCR (qPCR) was used to analyze the transcriptional
profiles on the genes encoding two retinoic-acid-induced gene I (RIG-I)-like
receptors (RLRs) and two interferons (INF-alpha and INF-gamma) in seven tissues
of an ATV-infected shelduck. After infection with ATV, both RLR genes were
significantly upregulated (P < 0.05) in all seven tissues. The peak expression
levels of the two RLR genes were observed at 24 hours postinfection (hpi) and
were higher in non-lymphoid tissues (liver, lung, kidney, and ovary) than in
lymphoid tissues (thymus, spleen and bursa). Although the transcription levels of
both IFN genes were also upregulated, they showed different time-dependent
expression patterns compared with those of the RLR genes. In addition, the
highest mRNA expression of the two IFN genes was observed in the ovary at 6 hpi.
This observation suggests that the ovary is the primary target tissue in ATV
infection and explains the clinical characteristics of the primary pathological
changes in the ovaries of ATV-infected ducks. Our results, for the first time,
elucidate the differential and coordinated expression profiles of two RLRs and
two IFNs in an ATV-infected shelduck.
PMID- 26427382
TI - Erratum to: Healthy Start: Description of a Safety Net for Perinatal Support
During Disaster Recovery.
PMID- 26427381
TI - Treatment effect, postoperative complications, and their reasons in juvenile
thoracic and lumbar spinal tuberculosis surgery.
AB - OBJECTIVE: Fifty-four juvenile cases under 18 years of age with thoracic and
lumbar spinal tuberculosis underwent focus debridement, deformity correction,
bone graft fusion, and internal fixation. The treatment effects, complications,
and reasons were analyzed retrospectively. MATERIAL AND METHOD: There were 54
juvenile cases under 18 years of age with thoracolumbar spinal tuberculosis. The
average age was 9.2 years old, and the sample comprised 38 males and 16 females.
The disease types included 28 thoracic cases, 17 thoracolumbar cases, and 9
lumbar cases. Nerve function was evaluated with the Frankel classification.
Thirty-six cases were performed with focus debridement and deformity correction
and were supported with allograft or autograft in mesh and fixed with pedicle
screws from a posterior approach. Eight cases underwent a combined anterior and
posterior surgical approach. Nine cases underwent osteotomy and deformity
correction, and one case received focus debridement. The treatment effects,
complications, and bone fusions were tracked for an average of 52 months.
RESULTS: According to the Frankel classification, paralysis was improved from 3
cases of B, 8 cases of C, 18 cases of D, and 25 cases of E preoperatively. This
improvement was found in 3 cases of C, 6 cases of D, and 45 cases of E at a final
follow-up postoperatively. No nerve dysfunction was aggravated. VAS was improved
from 7.8 +/- 1.7 preoperatively to 3.2 +/- 2.1 at final follow-up
postoperatively. ODI was improved from 77.5 +/- 17.3 preoperatively to 28.4 +/-
15.9 at final follow-up postoperatively. Kyphosis Cobb angle improved from 62.2
degrees +/- 3.7 degrees preoperatively to 37 degrees +/- 2.4 degrees at final
follow-up postoperatively. Both of these are significant improvements, and all
bone grafts were fused. Complications related to the operation occurred in 31.5%
(17/54) of cases. Six cases suffered postoperative aggravated kyphosis deformity,
eight cases suffered proximal kyphosis deformity, one case suffered pedicle
penetration, one case suffered failure of internal devices, and one case suffered
recurrence of tuberculosis. CONCLUSION: As long as the treatment plan is fully
prepared, the surgical option can achieve a satisfactory curative effect in
treating juvenile spinal tuberculosis despite some complications.
PMID- 26427383
TI - Significance of Lipolytic Enzymes in Pathogenesis and Treatment of Neglected
Diseases.
AB - Neglected diseases are infectious diseases that affect poor people of tropical
countries. Drug resistance, lower availability of funds and research hinder the
opportunities for the development of new drugs. The need for new drugs will
persist until pathogens are eradicated. This calls for understanding the disease
prognosis to initiate research for new drug targets and thus development of new
drugs. As drug development is complex and expensive process, in silico drug
development can aid in this regard by reducing time, effort and capital for the
quest of a "better drug" for such neglected diseases. Recent knowledge about the
genome and proteome has increased enthusiasm for the quest of new drug targets.
One such potential target can be lipases which are involved in the lipid
metabolism of pathogens. Lipases of pathogens have multitude of functions in many
patho-physiological processes including virulence, transmission, life cycle
development, modulation of host lipids and host immune responses. Thus the aim of
this review is to describe the significance of lipases in the life cycle and
pathogenesis of the pathogen and whether they can be used as drug targets. The
development of research in this direction has also been brought forward. This may
help in finding new drug targets for neglected disease.
PMID- 26427384
TI - Multi-output Model with Box-Jenkins Operators of Quadratic Indices for Prediction
of Malaria and Cancer Inhibitors Targeting Ubiquitin- Proteasome Pathway (UPP)
Proteins.
AB - The ubiquitin-proteasome pathway (UPP) is the primary degradation system of short
lived regulatory proteins. Cellular processes such as the cell cycle, signal
transduction, gene expression, DNA repair and apoptosis are regulated by this UPP
and dysfunctions in this system have important implications in the development of
cancer, neurodegenerative, cardiac and other human pathologies. UPP seems also to
be very important in the function of eukaryote cells of the human parasites like
Plasmodium falciparum, the causal agent of the neglected disease Malaria. Hence,
the UPP could be considered as an attractive target for the development of
compounds with Anti-Malarial or Anti-cancer properties. Recent online databases
like ChEMBL contains a larger quantity of information in terms of pharmacological
assay protocols and compounds tested as UPP inhibitors under many different
conditions. This large amount of data give new openings for the computer-aided
identification of UPP inhibitors, but the intrinsic data diversity is an obstacle
for the development of successful classifiers. To solve this problem here we used
the Bob-Jenkins moving average operators and the atom-based quadratic molecular
indices calculated with the software TOMOCOMD-CARDD (TC) to develop a
quantitative model for the prediction of the multiple outputs in this complex
dataset. Our multi-target model can predict results for drugs against 22
molecular or cellular targets of different organisms with accuracies above 70% in
both training and validation sets.
PMID- 26427385
TI - Pyrazinamide and Pyrazinoic Acid Derivatives Directed to Mycobacterial Enzymes
Against Tuberculosis.
AB - Tuberculosis (TB) is an infectious diseases responsible for thousands of deaths
worldwide. Due to the use of antimycobacterial drugs, TB prevalence seemed to be
controlled, but with the appearance of resistant tuberculosis cases, the concern
about the disease had become significant again, as well as the need for new
alternatives to TB treatment. Since pyrazinamide (PZA) is part of the firstline
agents in TB treatment, several derivatives of this drug were described, besides
pyrazinoic acid (POA) derivatives, the active form of PZA. POA has been used
mainly to design prodrugs to be activated by mycobacterial esterases, while PZA
derivatives should be activated specifically by the nicotinamidase/
pyrazinamidase (PZAse), or other PZAse-independent pathways. The intention of
this paper is to discuss the state of art of PZA and POA derivatives and their
activity against Mycobacterium tuberculosis and other mycobacteria, besides the
therapeutic potential. Focus was given in prodrugs and derivatives directed to
mycobacterial enzymes involved in its activation or mechanism of action.
PMID- 26427386
TI - Apolipoprotein E Isoforms and AMD.
AB - The cholesterol transporting protein apolipoprotein E (ApoE) occurs in three
allelic variants in humans unlike in other species. The resulting protein
isoforms E2, E3 and E4 exhibit differences in lipid binding, integrating into
lipoprotein particles and affinity for lipoprotein receptors. ApoE isoforms
confer genetic risk for several diseases of aging including atherosclerosis,
Alzheimer's disease, and age-related macular degeneration (AMD). A single E4
allele increases the risk of developing Alzheimer's disease, whereas the E2
allele is protective. Intriguingly, the E4 allele is protective in AMD. Current
thinking about different functions of ApoE isoforms comes largely from studies on
Alzheimer's disease. These data cannot be directly extrapolated to AMD since the
primary cells affected in these diseases (neurons vs. retinal pigment epithelium)
are so different. Here, we propose that ApoE serves a fundamentally different
purpose in regulating cholesterol homeostasis in the retinal pigment epithelium
and this could explain why allelic risk factors are flipped for AMD compared to
Alzheimer's disease.
PMID- 26427387
TI - Role of Chemokines in Shaping Macrophage Activity in AMD.
AB - Age-related macular degeneration (AMD) is a multifactorial disorder that affects
millions of individuals worldwide. While the advent of anti-VEGF therapy has
allowed for effective treatment of neovascular 'wet' AMD, no treatments are
available to mitigate the more prevalent 'dry' forms of the disease. A role for
inflammatory processes in the progression of AMD has emerged over a period of
many years, particularly the characterisation of leukocyte infiltrates in AMD
affected eyes, as well as in animal models. This review focuses on the burgeoning
understanding of chemokines in the retina, and their potential role in shaping
the recruitment and activation of macrophages in AMD. Understanding the
mechanisms which promote macrophage activity in the degenerating retina may be
key to controlling the potentially devastating consequences of inflammation in
diseases such as AMD.
PMID- 26427388
TI - Biology of p62/sequestosome-1 in Age-Related Macular Degeneration (AMD).
AB - p62/sequestosome-1 is a multidimensional protein that interacts with many
signaling factors, and regulates a variety of cellular functions including
inflammation, apoptosis, and autophagy. Our previous work has revealed in the
retinal pigment epithelium (RPE) that p62 promotes autophagy and simultaneously
enhances an Nrf2-mediated antioxidant response to protect against acute oxidative
stress. Several recent studies demonstrated that p62 contributes to NFkB mediated
inflammation and inflammasome activation under certain circumstances, raising the
question of whether p62 protects against or contributes to tissue injury. Herein,
we will review the general characteristics of p62, focusing on its pro- and anti
cell survival roles within different physiological/pathological contexts, and
discuss the potential of p62 as a therapeutic target for AMD.
PMID- 26427389
TI - Gene Structure of the 10q26 Locus: A Clue to Cracking the ARMS2/HTRA1 Riddle?
AB - Age-related macular degeneration (AMD) is a sight-threatening disorder of the
central retina. Being the leading cause of visual impairment in senior citizens,
it represents a major public health issue in developed countries. Genetic studies
of AMD identified two major susceptibility loci on chromosomes 1 and 10. The high
risk allele of the 10q26 locus encompasses three genes, PLEKHA1, ARMS2, and HTRA1
with high linkage disequilibrium and the individual contribution of the encoded
proteins to disease etiology remains controversial. While PLEKHA1 and HTRA1 are
highly conserved proteins, ARMS2 is only present in primates and can be detected
by using RT-PCR. On the other hand, there is no unequivocal evidence for the
existence of the encoded protein. However, it has been reported that risk
haplotypes only affect the expression of ARMS2 (but not of HTRA1), making ARMS2
the best candidate for being the genuine AMD gene within this locus. Yet,
homozygous carriers of a common haplotype carry a premature stop codon in the
ARMS2 gene (R38X) and therefore lack ARMS2, but this variant is not associated
with AMD. In this work we aimed at characterizing the diversity of transcripts
originating from this locus, in order to find new hints on how to resolve this
perplexing paradox. We found chimeric transcripts originating from the PLEKHA1
gene but ending in ARMS2. This finding may give a new explanation as to how
variants in this locus contribute to AMD.
PMID- 26427390
TI - Conditional Induction of Oxidative Stress in RPE: A Mouse Model of Progressive
Retinal Degeneration.
AB - An appropriate animal model is essential to screening drugs or designing a
treatment strategy for geographic atrophy. Since oxidative stress contributes to
the pathological changes of the retinal pigment epithelium (RPE), we are
reporting a new mouse AMD model of retinal degeneration by inducing mitochondrial
oxidative stress in RPE. Sod2 the gene for manganese superoxide dismutase (MnSOD)
was deleted in RPE layer using conditional knockout strategy. Fundus microscopy,
SD-OCT and electroretinography were used to monitor retinal structure and
function in living animals and microscopy was used to assess pathology post
mortem. Tissue specific deletion of Sod2 caused elevated signs of oxidative
stress, RPE dysfunction and showed some key features of AMD. Due to induction of
oxidative stress, the conditional knockout mice show progressive reduction in ERG
responses and thinning of outer nuclear layer (ONL) compared to non-induced
littermates.
PMID- 26427391
TI - Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration.
AB - Recent data have revealed epigenetic derangements and subsequent chromatin
remodeling as a potent biologic switch for chronic inflammation and cell survival
which are important therapeutic targets in the pathogenesis of several retinal
degenerations. Histone deacetylases (HDACs) are a major component of this system
and serve as a unique control of the chromatin remodeling process. With a
multitude of targeted HDAC inhibitors now available, their use in both basic
science and clinical studies has widened substantially. In the field of ocular
biology, there are data to suggest that HDAC inhibition may suppress
neovascularization and may be a possible treatment for retinitis pigmentosa and
dry age-related macular degeneration (AMD). However, the effects of these
inhibitors on cell survival and chemokine expression in the chorioretinal tissues
remain very unclear. Here, we review the multifaceted biology of HDAC activity
and pharmacologic inhibition while offering further insight into the importance
of this epigenetic pathway in retinal degenerations. Our laboratory
investigations aim to open translational avenues to advance dry AMD therapeutics
while exploring the role of acetylation on inflammatory gene expression in the
aging and degenerating retina.
PMID- 26427392
TI - A Brief Discussion on Lipid Activated Nuclear Receptors and their Potential Role
in Regulating Microglia in Age-Related Macular Degeneration (AMD).
AB - Age-related macular degeneration (AMD) is the leading cause of legal blindness
and visual impairment in individuals over 60 years of age in the Western World. A
common morphological denominator in all forms of AMD is the accumulation of
microglia within the sub-retinal space, which is believed to be a contributing
factor to AMD progression. However, the signaling pathway and molecular players
regulating microglial recruitment have not been completely identified. Multiple
in-vitro and in-vivo studies, to date, have highlighted the contributions of
nuclear receptor ligands in the treatment of inflammation related disorders such
as atherosclerosis and Alzheimer's disease. Given that inflammation and the
immune response play a vital role in the initiation and progression of AMD, in
this brief review we will highlight some of these studies with a particular focus
on the lipid activated "adopted orphan" nuclear receptors, the liver x receptors
(LXRs) and the peroxisome proliferator-activated receptors (PPARs). The results
of these studies strongly support the rationale that treatment with LXR and PPAR
ligands may ameliorate microglial activation in the sub-retinal space and
ultimately slow down or reverse the progression of AMD.
PMID- 26427393
TI - Extracellular Matrix Alterations and Deposit Formation in AMD.
AB - Age related macular degeneration (AMD) is the primary cause of vision loss in the
western world (Friedman et al., Arch Ophthalmol 122:564-572, 2004). The first
clinical indication of AMD is the presence of drusen. However, with age and prior
to the formation of drusen, extracellular basal deposits accumulate between the
retinal pigment epithelium (RPE) and Bruch's membrane (BrM). Many studies on the
molecular composition of the basal deposits and drusen have demonstrated the
presence of extracellular matrix (ECM) proteins, complement components and
cellular debris. The evidence reviewed here suggests that alteration in RPE cell
function might be the primary cause for the accumulation of ECM and cellular
debri found in basal deposits. Further studies are obviously needed in order to
unravel the specific pathways that lead to abnormal formation of ECM and
complement activation.
PMID- 26427394
TI - The NLRP3 Inflammasome and its Role in Age-Related Macular Degeneration.
AB - Age related macular degeneration (AMD) is the most common cause of blindness
among people of 65 years and older in developed countries (Klein and Klein,
Invest Ophthalmol Vis Sci 54:7395-7401, 2013). Recent advances in dry AMD
research points towards an important role of the inflammatory response in the
development of the disease. The presence of inflammatory cells, antibodies,
complement factors and pro-inflammatory cytokines in AMD retinas and drusen
indicates that the immune system could be an important driving force in dry AMD.
The NLRP3 inflammasome has been proposed as an integrator of process associated
with AMD and the induction of inflammation. Herein we summarize the most recent
studies that attempt to understand the role of the NLRP3 inflammasome in AMD.
PMID- 26427395
TI - Oxidative Stress and the Nrf2 Anti-Oxidant Transcription Factor in Age-Related
Macular Degeneration.
AB - Age-related macular degeneration (AMD) is the leading cause of acquired and
irreversible blindness among elderly Americans. Most AMD patients have the dry
form of the disease (dAMD) for which reliable therapies are lacking. A major
obstacle to the development of effective treatments is a deficit in our
understanding of what triggers dAMD onset. This is particularly the case with
respect to the events that cause retinal pigment epithelial (RPE) cells to
transition from a state of health and homeostasis to one of dysfunction and
atrophy. These cells provide critical support to the photoreceptors and their
atrophy often precipitates photoreceptor death in dAMD. Chronic oxidative stress
is a primary driver of age-dependent, RPE atrophy. Sources of this stress have
been identified (e.g., cigarette smoke, photooxidized bisretinoids), but we still
do not understand how these stressors damage RPE constituents or what age
dependent changes undermine the cytoprotective systems in the RPE. This review
focuses on Nrf2, the master antioxidant transcription factor, and its role in the
RPE during aging and dAMD onset.
PMID- 26427396
TI - Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal
Disease.
AB - Age-related retinal diseases, such as age-related macular degeneration (AMD) and
glaucoma, contain features of chronic retinal inflammation that may promote
disease progression. However, the relationship between aging and
neuroinflammation is unclear. Microglia are long-lived, resident immune cells of
the retina, and mediate local neuroinflammatory reactions. We hypothesize that
aging changes in microglia may be causally linked to neuroinflammatory changes
underlying age-dependent retinal diseases. Here, we review the evidence for (1)
how the retinal microglial phenotype changes with aging, (2) the factors that
drive microglial aging in the retina, and (3) aging-related changes in microglial
gene expression. We examine how these aspects of microglial aging changes may
relate to pathogenic mechanisms of immune dysregulation driving the progression
of age-related retinal disease. These relationships can highlight microglial
aging as a novel target for the prevention and treatment of retinal disease.
PMID- 26427397
TI - VEGF-A and the NLRP3 Inflammasome in Age-Related Macular Degeneration.
AB - The pathomechanisms that lead to age-related macular degeneration (AMD) are only
partially understood. The NLRP3 inflammasome has been shown to be activated in
the retinal pigment epithelium (RPE) in eyes with AMD. However, it is not known
whether inflammasome activation is a cause or consequence of pathologic changes
in AMD. A roadblock to defining the role of inflammasome activation and pathways
that regulate it for AMD has been the lack of a mouse model that forms AMD-like
pathologies in an age-dependent manner in which the role of the inflammasome can
be investigated using genetic studies. We have recently identified such a mouse
model, in which increased VEGF-A levels result in early degenerative changes of
the RPE, followed by cardinal features of both nonexudative and neovascular AMD.
Importantly, higher VEGF-A levels lead to increased oxidative damage and a sub
retinal inflammatory infiltrate that are associated with NLRP3 inflammasome
activation in the RPE. Targeting the NLRP3 inflammasome inhibited AMD-like
pathologies in these mice. These findings suggest that inhibiting the NLRP3
inflammasome or pathways that regulate it may provide novel therapeutic
approaches for the treatment of both forms of AMD.
PMID- 26427398
TI - Interrelation Between Oxidative Stress and Complement Activation in Models of Age
Related Macular Degeneration.
AB - Millions of individuals older than 50-years suffer from age-related macular
degeneration (AMD). Associated with this multifactorial disease are polymorphisms
of complement factor genes and a main environmental risk factor-oxidative stress.
Until now the linkage between these risk factors for AMD has not been fully
understood. Recent studies, integrating results on oxidative stress, complement
activation, epidemiology and ocular pathology suggested the following sequence in
AMD-etiology: initially, chronic oxidative stress results in modification of
proteins and lipids in the posterior of the eye; these tissue alterations trigger
chronic inflammation, involving the complement system; and finally, invasive
immune cells facilitate pathology in the retina. Here, we summarize the results
for animal studies which aim to elucidate this molecular interplay of oxidative
events and tissue-specific complement activation in the eye.
PMID- 26427399
TI - Gene-Diet Interactions in Age-Related Macular Degeneration.
AB - Age-related macular degeneration (AMD) is a prevalent blinding disease,
accounting for roughly 50 % of blindness in developed nations. Very significant
advances have been made in terms of discovering genetic susceptibilities to AMD
as well as dietary risk factors. To date, nutritional supplementation is the only
available treatment option for the dry form of the disease known to slow
progression of AMD. Despite an excellent understanding of genes and nutrition in
AMD, there is remarkably little known about gene-diet interactions that may
identify efficacious approaches to treat individuals. This review will summarize
our current understanding of gene-diet interactions in AMD with a focus on animal
models and human epidemiological studies.
PMID- 26427400
TI - Challenges in the Development of Therapy for Dry Age-Related Macular
Degeneration.
AB - Dry age-related macular degeneration (AMD), a multifactorial progressive
degenerative disease of the retinal photoreceptors, pigmented epithelium and
Bruch's membrane/choroid in central retina, causes visual impairment in millions
of elderly people worldwide. The only available therapy for this disease is the
over-the-counter (OTC) multi-vitamins plus macular xanthophyll
(lutein/zeaxanthin) which attempts to block the damages of oxidative stress and
ionizing blue light. Therefore development of dry AMD prescribed treatment is a
pressing unmet medical need. However, this effort is currently hindered by many
challenges, including an incomplete understanding of the mechanism of
pathogenesis that leads to uncertain targets, confounded by not yet validated
preclinical models and the difficulty to deliver the drugs to the posterior
segment of the eye. Additionally, with slow disease progression and a less than
ideal endpoint measurement method, clinical trials are necessarily large, lengthy
and expensive. Increased commitment to research and development is an essential
foundation for dealing with these problems. Innovations in clinical trials with
novel endpoints, nontraditional study designs and the use of surrogate diseases
might shorten the study time, reduce the patient sample size and consequently
lower the budget for the development of the new therapies for the dry AMD.
PMID- 26427401
TI - Nanoceria: a Potential Therapeutic for Dry AMD.
AB - Age-related macular degeneration (AMD) is the leading cause of blinding diseases.
The "dry" form of AMD is the most common form of AMD. In contrast to the
treatable neovascular (wet) AMD, no effective treatment is available for dry AMD.
In this review, we summarize the animal models and therapeutic strategies for dry
AMD. The novel candidates as potential treatment targets and the potential
effectiveness of nanoceria as a treatment of dry AMD are also discussed.
PMID- 26427402
TI - beta-amyloidopathy in the Pathogenesis of Age-Related Macular Degeneration in
Correlation with Neurodegenerative Diseases.
AB - Involvement of new biotechnology and genetic engineering methods to the study of
the aging organism allowed to select a group of neurodegenerative diseases (NDD)
which have a similar mechanism of pathogenesis including pathological processes
of protein aggregation and its deposition in the structures of nerve tissue. The
development of eye and brain from one embryonic germ layer, community of
ethiopathogenetic and morphological manifestations of age-related macular
degeneration (AMD) and Alzheimer's disease (AD), a common pathway of beta-amyloid
precursor protein (APP) are associated with the pathological aggregation of
fibrillar beta-amyloid (Abeta) protein and the development of beta-amyloidopathy
in structural elements of the eye and the brain. The review demonstrates the
keynote of AMD and AD pathogenesis is beta-amyloidopathy that is a manifestation
of proteinopathy leading to cytotoxicity, neurodegeneration and the development
of pathological apoptosis activated by the formation of intracellular Abeta. This
view on the problem predetermines the development of new strategies for the
creating of ophthalmogeriatric and neuroprotective drugs affecting the
pathogenesis and including all stages of Abeta formation and pathological
aggregation.
PMID- 26427403
TI - Different Mutations in ELOVL4 Affect Very Long Chain Fatty Acid Biosynthesis to
Cause Variable Neurological Disorders in Humans.
AB - All mammalian cell membranes are characterized by amphipathic lipid molecules
that interact with proteins to confer structural and functional properties on the
cell. The predominant lipid species are phospholipids, glycolipids, sphingolipids
and cholesterol. These lipids contain fatty acids with variable hydrocarbon chain
lengths between C14-C40, either saturated or unsaturated, that are derived from
diet, synthesized de novo, or elongated from shorter chain fatty acids by fatty
acid elongase enzymes. One member of the family of elongases, ELOngation of Very
Long chain fatty acids-4 (ELOVL4), mediates the biosynthesis of both saturated
and unsaturated very long chain fatty acids (VLC-FA; > C26) in the retina,
meibomian gland, brain, skin, and testis. Different mutations in ELOVL4 cause
tissue-specific maculopathy and/or neuro-ichthyotic disorders. The goal of this
mini-review is to highlight how different mutations in ELOVL4 can cause variable
phenotypic disorder, and propose a possible mechanism, based on the role of fatty
acids in membranes, which could explain the different phenotypes.
PMID- 26427404
TI - Mouse Models of Stargardt 3 Dominant Macular Degeneration.
AB - Stargardt type 3 macular degeneration is dependent on a dominant defect in a
single gene, ELOVL4 (elongase of very long chain fatty acids 4). The encoded
enzyme, ELOVL4, is required for the synthesis of very long chain polyunsaturated
fatty acids (VLC-PUFAs), a rare class of > C24 lipids. In vitro expression
studies suggest that mutated ELOVL4(STGD3) proteins fold improperly, resulting in
ER stress and formation of cytosolic aggresomes of wild type and mutant ELOVL4.
Although a number of mouse models have been developed to determine whether
photoreceptor cell loss in STGD3 results from depletion of VLC-PUFAs, aggresome
dependent cell stress or a combination of these two factors, none of these models
adequately recapitulates the disease phenotype in humans. Thus, the precise
molecular mechanism by which ELOVL4 mutation causes photoreceptor degeneration in
mice and in human patients remains to be characterized. This mini review compares
and evaluates current STGD3 mouse models and determines what conclusions can be
drawn from past work.
PMID- 26427405
TI - Current Progress in Deciphering Importance of VLC-PUFA in the Retina.
AB - Stargardt-like macular dystrophy-3 (STGD3) is a juvenile-onset disease caused by
mutations in ELOVL4 (elongation of very long fatty acids-4). This gene product
catalyzes the elongation of long chain saturated and polyunsaturated fatty acids
(LC-FAs and LC-PUFAs) into very long chain FAs and PUFAs (VLC-FAs and VLC-PUFAs).
These mutations cause a frame shift in the ELOVL4 transcript, introducing a
premature stop codon that results in the translation of a truncated protein that
has lost a C-terminus endoplasmic reticulum (ER) retention/retrieval signal. The
truncated protein is not targeted to the ER, the site of very long-chain PUFA
(VLC-PUFA; 28-40 carbons) synthesis. Expression of the ELOVL4 gene is limited
mainly to the brain, testis, skin, and photoreceptor cells of the retina. While
the skin and brain contain very long chain saturated fatty acids (VLC-FAs), the
other tissues expressing ELOVL4 contain VLC-PUFAs, with sperm and the retina
having the highest levels. This review focuses on the current information
available concerning the role of VLC-PUFAs in the retina.
PMID- 26427406
TI - Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy: Similarities to Age
Related Macular Degeneration and Potential Therapies.
AB - Fibulin-3 (F3) is a secreted, disulfide-rich glycoprotein which is expressed in a
variety of tissues within the body, including the retina. An Arg345Trp (R345W)
mutation in F3 was identified as the cause of a rare retinal dystrophy, Malattia
Leventinese/Doyne Honeycomb Retinal Dystrophy (ML/DHRD). ML/DHRD shares many
phenotypic similarities with age-related macular degeneration (AMD). The most
prominent feature of ML/DHRD is the development of radial or honeycomb patterns
of drusen which can develop as early as adolescence. Two independent mouse models
of ML/DHRD show evidence of complement activation as well as retinal pigment
epithelium (RPE) atrophy, strengthening the phenotypic connection with AMD.
Because of its similarities with AMD, ML/DHRD is receiving increasing interest as
a potential surrogate disease to study the underpinnings of AMD. This mini-review
summarizes the current knowledge of F3 and points toward potential therapeutic
strategies which directly or indirectly target cellular dysfunction associated
with R345W F3.
PMID- 26427407
TI - Hsp90 as a Potential Therapeutic Target in Retinal Disease.
AB - The molecular chaperone heat shock protein 90 (Hsp90) is a pivotal cellular
regulator involved in the folding, activation and assembly of a wide range of
proteins. Hsp90 has multiple roles in the retina and the use of different Hsp90
inhibitors has been shown to prevent retinal degeneration in models of retinitis
pigmentosa and age-related macular degeneration. Hsp90 is also a potential target
in uveal melanoma. Mechanistically, Hsp90 inhibition can evoke a dual response in
the retina; stimulating a stress response with molecular chaperone expression.
Thereby leading to an improvement in visual function and photoreceptor survival;
however, prolonged inhibition can also stimulate the degradation of Hsp90 client
proteins potentially deleteriously affect vision. Here, we review the multiple
roles of Hsp90 in the retina and the therapeutic potential of Hsp90 as a target.
PMID- 26427408
TI - Leber Congenital Amaurosis: Genotypes and Retinal Structure Phenotypes.
AB - Leber congenital amaurosis (LCA) patients of 10 known genotypes (n = 24; age
range, 3-25 years) were studied clinically and by optical coherence tomography
(OCT). Comparisons were made between OCT results across the horizontal meridian
(central 60(o)) of the patients. Three patterns were identified. First, there
were LCA genotypes with unusual and readily identifiable patterns, such as near
normal outer nuclear layer (ONL) across the central retina or severely dysplastic
retina. Second, there were genotypes with well-formed foveal architecture but
only residual central islands of normal or reduced ONL thickness. Third, some
genotypes showed central ONL losses or dysmorphology suggesting early macular
disease or foveal maldevelopment. Objective in vivo morphological features could
complement other phenotypic characteristics and help guide genetic testing of LCA
patients or at least permit a differential diagnosis of genotypes to be made in
the clinic.
PMID- 26427409
TI - A Chemical Mutagenesis Screen Identifies Mouse Models with ERG Defects.
AB - Mouse models provide important resources for many areas of vision research,
pertaining to retinal development, retinal function and retinal disease. The
Translational Vision Research Models (TVRM) program uses chemical mutagenesis to
generate new mouse models for vision research. In this chapter, we report the
identification of mouse models for Grm1, Grk1 and Lrit3. Each of these is
characterized by a primary defect in the electroretinogram. All are available
without restriction to the research community.
PMID- 26427410
TI - Ablation of Chop Transiently Enhances Photoreceptor Survival but Does Not Prevent
Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin.
AB - RHO (Rod opsin) encodes a G-protein coupled receptor that is expressed
exclusively by rod photoreceptors of the retina and forms the essential
photopigment, rhodopsin, when coupled with 11-cis-retinal. Many rod opsin disease
-mutations cause rod opsin protein misfolding and trigger endoplasmic reticulum
(ER) stress, leading to activation of the Unfolded Protein Response (UPR) signal
transduction network. Chop is a transcriptional activator that is induced by ER
stress and promotes cell death in response to chronic ER stress. Here, we
examined the role of Chop in transgenic mice expressing human P23H rhodopsin
(hP23H Rho Tg) that undergo retinal degeneration. With the exception of one time
point, we found no significant induction of Chop in these animals and no
significant change in retinal degeneration by histology and electrophysiology
when hP23H Rho Tg animals were bred into a Chop (-/-) background. Our results
indicate that Chop does not play a significant causal role during retinal
degeneration in these animals. We suggest that other modules of the ER stress
induced UPR signaling network may be involved photoreceptor disease induced by
P23H rhodopsin.
PMID- 26427411
TI - Identification of a Novel Gene on 10q22.1 Causing Autosomal Dominant Retinitis
Pigmentosa (adRP).
AB - Whole-genome linkage mapping identified a region on chromosome 10q21.3-q22.1 with
a maximum LOD score of 3.0 at 0 % recombination in a six-generation family with
autosomal dominant retinitis pigmentosa (adRP). All known adRP genes and X-linked
RP genes were excluded in the family by a combination of methods. Whole-exome
next-generation sequencing revealed a missense mutation in hexokinase 1, HK1
c.2539G > A, p.Glu847Lys, tracking with disease in all affected family members.
One severely-affected male is homozygous for this region by linkage analysis and
has two copies of the mutation. No other potential mutations were detected in the
linkage region nor were any candidates identified elsewhere in the genome.
Subsequent testing detected the same mutation in four additional, unrelated adRP
families, for a total of five mutations in 404 probands tested (1.2 %). Of the
five families, three are from the Acadian population in Louisiana, one is French
Canadian and one is Sicilian. Haplotype analysis of the affected chromosome in
each family and the homozygous individual revealed a rare, shared haplotype of
450 kb, suggesting an ancient founder mutation. HK1 is a widely-expressed gene,
with multiple, abundant retinal transcripts, coding for hexokinase 1. Hexokinase
catalyzes phosphorylation of glucose to glusose-6-phospate, the first step in
glycolysis. The Glu847Lys mutation is in a highly-conserved site, outside of the
active site or known functional sites.
PMID- 26427412
TI - FAM161A and TTC8 are Differentially Expressed in Non-Allelelic Early Onset
Retinal Degeneration.
AB - Ciliary genes FAM161A and TTC8 have been implicated in retinal degeneration (RD)
in humans and in dogs. The identification of FAM161A and TTC8 mutations in canine
RD is exciting as there is the potential to develop novel large animal models for
RD. However, the disease phenotypes in the dog and the roles of abnormal genes in
disease pathology have yet to be fully characterized. The present study evaluated
the expression patterns of FAM161A and TTC8 during normal retinal development in
dogs, and in three non-allelic, early onset canine RD models at critical time
points of the disease: RCD1, XLPRA2 and ERD. Both genes were differentially
expressed in RCD1 and ERD, but not in XLPRA2. These results add evidence to the
hypothesis that (a) mutations in many retinal genes have a cascade effect on the
expression of multiple, possibly unrelated genes and (b) a large number and wide
range of genes probably contribute to RD in general.
PMID- 26427413
TI - Mutations in the Dynein1 Complex are Permissible for Basal Body Migration in
Photoreceptors but Alter Rab6 Localization.
AB - The photoreceptor outer segment is a specialized primary cilium, and anchoring of
the basal body at the apical membrane is required for outer segment formation. We
hypothesized that basal body localization and outer segment formation would
require the microtubule motor dynein 1 and analyzed the zebrafish cannonball and
mike oko mutants, which carry mutations in the heavy chain subunit of cytoplasmic
dynein 1 (dync1h1) and the p150(Glued) subunit of Dynactin (dctn1a). The
distribution of Rab6, a player in the post-Golgi trafficking of rhodopsin, was
also examined. Basal body docking was unaffected in both mutants, but Rab6
expression was reduced. The results suggest that dynein 1 is dispensable for
basal body docking but that outer segment defects may be due to defects in post
Golgi trafficking.
PMID- 26427414
TI - RDS Functional Domains and Dysfunction in Disease.
AB - The photoreceptor specific tetraspanin protein retina degeneration slow (RDS) is
a critical component of the machinery necessary for the formation of rod and cone
outer segments. Over 80 individual pathogenic mutations in RDS have been
identified in human patients that lead to a wide variety of retinal degenerative
diseases including retinitis pigmentosa, cone-rod dystrophy, and various forms of
macular dystrophy. RDS-associated disease is characterized by a high degree of
variability in phenotype and penetrance, making analysis of the underlying
molecular mechanisms of interest difficult. Here we summarize our modern
understanding of RDS functional domains and oligomerization and how disruption of
these domains and complexes could contribute to the variety of disease
pathologies seen in human patients with RDS mutations.
PMID- 26427415
TI - TULP1 Missense Mutations Induces the Endoplasmic Reticulum Unfolded Protein
Response Stress Complex (ER-UPR).
AB - Mutations in the TULP1 gene are associated with early-onset retinitis pigmentosa
(RP); however, the molecular mechanisms related to the deleterious effects of
TULP1 mutations remains unknown. Several studies have shown that misfolded
proteins secondary to genetic mutations can accumulate within the endoplasmic
reticulum (ER), causing activation of the unfolded protein response (UPR) complex
followed by cellular apoptosis. We hypothesize that TULP1 mutations produce
misfolded protein products that accumulate in the ER and induce cellular
apoptosis via the UPR. To test our hypothesis, we first performed three in-silico
analyses of TULP1 missense mutations (I459K, R420P and F491L), which predicted
misfolded protein products. Subsequently, the three mutant TULP1-GFP constructs
and wild-type (wt) TULP1-GFP were transiently transfected into hTERT-RPE-1 cells.
Staining of cells using ER tracker followed by confocal microscopy showed wt
TULP1 localized predominantly to the cytoplasm and plasma membrane. In contrast,
all three mutant TULP1 proteins revealed cytoplasmic punctate staining which co
localized with the ER. Furthermore, western blot analysis of cells expressing
mutant TULP1 proteins revealed induction of downstream targets of the ER-UPR
complex, including BiP/GPR-78, phosphorylated-PERK (Thr980) and CHOP. Our in
vitro analyses suggest that mutant TULP1 proteins are misfolded and accumulate
within the ER leading to induction of the UPR stress response complex.
PMID- 26427416
TI - Understanding Cone Photoreceptor Cell Death in Achromatopsia.
AB - Colour vision is only achieved in the presence of healthy and functional cone
photoreceptors found in the retina. It is an essential component of human vision
and usually the first complaint patients undergoing vision degeneration have is
the loss of daylight colour vision. Therefore, an understanding of the biology
and basic mechanisms behind cone death under the degenerative state of retinal
dystrophies and how the activation of the apoptotic pathway is triggered will
provide valuable knowledge. It will also have broader applications for a spectrum
of visual disorders and will be critical for future advances in translational
research.
PMID- 26427417
TI - Geranylgeranylacetone Suppresses N-Methyl-N-nitrosourea-Induced Photoreceptor
Cell Loss in Mice.
AB - Retinitis pigmentosa is a disease characterized by the loss of photoreceptor
cells. The N-methyl-N-nitrosourea (MNU)-induced retinal degeneration model is
widely used to study the mechanism of these retinal degenerative disorders
because of its selective photoreceptor cell death. As for the cell death
mechanism of MNU, calcium-calpain activation and lipid peroxidation processes are
involved in the initiation of this cell death. Although such molecular mechanisms
of the MNU-induced cell death have been described, the total image of the cell
death is still obscure. Heat shock protein 70 (HSP70) has been shown to function
as a chaperon molecule to protect cells against environmental and physiological
stresses. In this study, we investigated the effect of geranylgeranylacetone
(GGA), an accylic polyisoprenoid, on MNU-induced photoreceptor cell loss. HSP70
induction by GGA was effective against MNU-induced photoreceptor cell loss as a
result of its ability to prevent HSP70 degradation. The data indicate that GGA
may help to suppress the onset and progression of retinitis pigmentosa.
PMID- 26427418
TI - My Retina TrackerTM: An On-line International Registry for People Affected with
Inherited Orphan Retinal Degenerative Diseases and their Genetic Relatives - A
New Resource.
AB - My Retina TrackerTM is a new on-line registry for people affected with inherited
orphan retinal degenerative diseases, and their unaffected, genetic relatives.
Created and supported by the Foundation Fighting Blindness, it is an
international resource designed to capture the disease from the perspective of
the registry participant and their retinal health care providers. The registry
operates under an Institutional Review Board (IRB)-approved protocol and allows
sharing of de-identified data with participants, researchers and clinicians. All
participants sign an informed consent that includes selecting which data they
wish to share. There is no minimum age of participation. Guardians must sign on
behalf of minors, and children between the ages of 12 to 17 also sign an informed
assent. Participants may compare their disease to others in the registry using
graphical interpretations of the aggregate registry data. Researchers and
clinicians have two levels of access. The first provides an interface to
interrogate all data fields registrants have agreed to share based on their
answers in the IRB informed consent. The second provides a route to contact
people in the registry who may be eligible for studies or trials, through the
Foundation.
PMID- 26427419
TI - A Mini-review: Animal Models of GUCY2D Leber Congenital Amaurosis (LCA1).
AB - GUCY2D encodes retinal guanylate cylase-1 (retGC1), a protein that plays a
pivotal role in the recovery phase of phototransduction. Mutations in GUCY2D are
associated with a leading cause of recessive Leber congenital amaurosis (LCA1).
Patients present within the first year of life with aberrant or unrecordable
electroretinogram (ERG), nystagmus and a relatively normal fundus. Aside from
abnormalities in the outer segments of foveal cones and, in some patients, foveal
cone loss, LCA1 patients retain normal retinal laminar architecture suggesting
they may be good candidates for gene replacement therapy. Several animal models
of LCA1, both naturally occurring and engineered, have been characterized and
provide valuable tools for translational studies. This mini-review will summarize
the phenotypes of these models and describe how each has been instrumental in
proof of concept studies to develop a gene replacement therapy for GUCY2D-LCA1.
PMID- 26427420
TI - A Comprehensive Review of Mutations in the MERTK Proto-Oncogene.
AB - Phagocytosis and elimination of shed aged photoreceptor outer segments (POS) by
retinal pigment epithelial cells is crucial for photoreceptor function and
survival. Genetic studies on a natural animal model of recessive retinal
degeneration allowed the identification of MerTK, the gene encoding the surface
receptor required for POS internalization. Following this discovery, screenings
of DNA samples from patients have revealed that MERTK mutations cause retinal
degenerations in humans. MERTK patients present some of the classical symptoms of
retinitis pigmentosa, but it is atypical in that the disease develops very early
during childhood and the macula is also involved early on. Therefore, the
phenotype ought to be qualified as a rod-cone dystrophy. Recently, MERTK has been
implicated in various types of cancers and sclerosis. This review identifies the
different MERTK mutations known so far and describes associated pathologies.
PMID- 26427421
TI - New Developments in Murine Imaging for Assessing Photoreceptor Degeneration In
Vivo.
AB - Optical Coherence Tomography (OCT) is a powerful clinical tool that measures near
infrared light backscattered from the eye and other tissues. OCT is used for
assessing changes in retinal structure, including layer thicknesses, detachments
and the presence of drusen in patient populations. Our custom-built OCT system
for the mouse eye quantitatively images all layers of the neural retinal, the
RPE, Bruchs' membrane and the choroid. Longitudinal assessment of the same
retinal region reveals that the relative intensities of retinal layers are highly
stable in healthy tissue, but show progressive increases in intensity in a model
of retinal degeneration. The observed changes in OCT signal have been correlated
with ultrastructural disruptions that were most dramatic in the inner segments
and nuclei of the rods. These early changes in photoreceptor structure coincided
with activation of retinal microglia, which migrated vertically from the inner to
the outer retina to phagocytose photoreceptor cell bodies (Levine et al., Vis Res
102:71-79, 2014). We conclude that quantitative analysis of OCT light scattering
signals may be a useful tool for early detection and subcellular localization of
cell stress prior to cell death, and for assessing the progression of
degenerative disease over time. Future efforts to develop sensitive approaches
for monitoring microglial dynamics in vivo may likewise elucidate earlier signs
of cellular stress during retinal degeneration.
PMID- 26427422
TI - Reliability and Repeatability of Cone Density Measurements in Patients with
Congenital Achromatopsia.
AB - Adaptive optics scanning light ophthalmoscopy (AOSLO) allows non-invasive
assessment of the cone photoreceptor mosaic. Confocal AOSLO imaging of patients
with achromatopsia (ACHM) reveals an altered reflectivity of the remaining cone
structure, making identification of the cells more challenging than in normal
retinas. Recently, a "split-detector" AOSLO imaging method was shown to enable
direct visualization of cone inner segments in patients with ACHM. Several
studies have demonstrated gene replacement therapy effective in restoring cone
function in animal models of ACHM and human trials have on the horizon, making
the ability to reliably assess cone structure increasingly important. Here we
sought to examine whether absolute estimates of cone density obtained from split
detector and confocal AOSLO images differed from one another and whether the
inter- and intra-observer reliability is significantly different between these
modes. These findings provide an important foundation for evaluating the role of
these images as tools to assess the efficacy of future gene therapy trials.
PMID- 26427424
TI - Interpretation of Flood-Illuminated Adaptive Optics Images in Subjects with
Retinitis Pigmentosa.
AB - The purpose of this study was to correlate features on flood-illuminated adaptive
optics (AO) images with color fundus, fundus autofluorescence (FAF) and spectral
domain optical coherence tomography (SD-OCT) images in patients with retinitis
pigmentosa (RP). We imaged 39 subjects diagnosed with RP using the rtx1TM flood
illuminated AO camera from Imagine Eyes (Orsay, France). We observed a
correlation between hyper-autofluoresence changes on FAF, disruption of the
interdigitation zone (IZ) on SD-OCT and loss of reflective cone profiles on AO.
Four main patterns of cone-reflectivity were seen on AO: presumed healthy cone
mosaics, hypo-reflective blurred cone-like structures, higher frequency
disorganized hyper-reflective spots, and lower frequency hypo-reflective spots.
These regions were correlated to progressive phases of cone photoreceptor
degeneration observed using SD-OCT and FAF. These results help provide
interpretation of en face images obtained by flood-illuminated AO in subjects
with RP. However, significant ambiguity remains as to what truly constitutes a
cone, especially in areas of degeneration. With further refinements in
technology, flood illuminated AO imaging has the potential to provide rapid,
standardized, longitudinal and lower cost imaging in patients with retinal
degeneration.
PMID- 26427423
TI - Quantitative Fundus Autofluorescence in Best Vitelliform Macular Dystrophy: RPE
Lipofuscin is not Increased in Non-Lesion Areas of Retina.
AB - Since the lipofuscin of retinal pigment epithelial (RPE) cells has been
implicated in the pathogenesis of Best vitelliform macular dystrophy, we
quantified fundus autofluorescence (quantitative fundus autofluorescence, qAF) as
an indirect measure of RPE lipofuscin levels. Mean non-lesion qAF was found to be
within normal limits for age. By spectral domain optical coherence tomography (SD
OCT) vitelliform lesions presented as fluid-filled subretinal detachments
containing reflective material. We discuss photoreceptor outer segment debris as
the source of the intense fluorescence of these lesions and loss of anion channel
functioning as an explanation for the bullous photoreceptor-RPE detachment.
Unexplained is the propensity of the disease for central retina.
PMID- 26427425
TI - Intra-familial Similarity of Wide-Field Fundus Autofluorescence in Inherited
Retinal Dystrophy.
AB - To examine the similarity of wide-field fundus autofluorescence (FAF) imaging in
inherited retinal dystrophy between siblings and between parents and their
children. The subjects included 17 siblings (12 with retinitis pigmentosa and 5
with cone rod dystrophy) and 10 parent-child pairs (8 with retinitis pigmentosa
and 2 with cone rod dystrophy). We quantified the similarity of wide-field FAF
using image processing techniques of cropping, binarization, superimposition, and
subtraction. The estimated similarity of the siblings was compared with that of
the parent-child pairs and that of the age-matched unrelated patients. The
similarity between siblings was significantly higher that of parent-child pairs
or that of age-matched unrelated patients (P = 0.004 and P = 0.049,
respectively). Wide-field FAF images were similar between siblings with inherited
retinal dystrophy but different between parent-child pairs. This suggests that
aging is a confounding factor in genotype-phenotype correlation studies.
PMID- 26427426
TI - Wide-Field Fundus Autofluorescence for Retinitis Pigmentosa and Cone/Cone-Rod
Dystrophy.
AB - Retinitis pigmentosa and cone/cone-rod dystrophy are inherited retinal diseases
characterized by the progressive loss of rod and/or cone photoreceptors. To
evaluate the status of rod/cone photoreceptors and visual function, visual acuity
and visual field tests, electroretinogram, and optical coherence tomography are
typically used. In addition to these examinations, fundus autofluorescence (FAF)
has recently garnered attention. FAF visualizes the intrinsic fluorescent
material in the retina, which is mainly lipofuscin contained within the retinal
pigment epithelium. While conventional devices offer limited viewing angles in
FAF, the recently developed Optos machine enables recording of wide-field FAF.
With wide-field analysis, an association between abnormal FAF areas and visual
function was demonstrated in retinitis pigmentosa and cone-rod dystrophy. In
addition, the presence of "patchy" hypoautofluorescent areas was found to be
correlated with symptom duration. Although physicians should be cautious when
interpreting wide-field FAF results because the peripheral parts of the image are
magnified significantly, this examination method provides previously unavailable
information.
PMID- 26427427
TI - The Development of a Cat Model of Retinal Detachment and Re-attachment.
AB - We present an optimized surgical technique for feline retinal detachment which
allows for natural re-attachment, reduces retinal scarring and vitreal bands, and
allows central placement of the detachment in close proximity to the optic nerve.
This enables imaging via Optical Coherence Tomography (OCT) and multifocal
electroretinography (mfERG) analysis. Ideal detachment conditions involve a
lensectomy followed by a three-port pars plana vitrectomy. A 16-20 % retinal
detachment is induced by injecting 8 % C3F8 gas into the subretinal space in the
central retina with a 42G cannula. The retinal detachment resolves approximately
6 weeks post-surgery. Imaging is enhanced by using a 7.5 and 20 diopter lens for
OCT and mfERG fundus imaging, respectively, to compensate for the removed lens.
PMID- 26427428
TI - The Role of X-Chromosome Inactivation in Retinal Development and Disease.
AB - The expression of X-linked genes is equalized between males and females in
mammalian species through X-Chromosome inactivation (XCI). Every cell in a female
mammalian embryo randomly chooses one X Chromosome for epigenetic silencing at
the 8-16 cell stage, resulting in a Gaussian distribution of XCI ratios with a
peak at 50:50. At the tail extremes of this distribution, X-linked recessive
mutations can manifest in disease in female carriers if the mutant allele is
disproportionately active. The role of XCI skewing, if any, in X-linked retinal
disease is still unknown, although many have speculated that such skewing
accounts for phenotypic variation in female carriers of X-linked retinitis
pigmentosa (XlRP). Some investigators have used clinical findings such as tapetal
like reflex, pigmentary changes, and multifocal ERG parameters to approximate XCI
patches in the retina. These studies are limited by small cohorts and the
relative inaccessibility of retinal tissue for genetic and epigenetic analysis.
Although blood has been used as a proxy for other tissues in determining XCI
ratios, blood XCI skews with age out of proportion to other tissues and may not
accurately reflect retinal XCI ratios. Future investigations in determining
retinal XCI ratios and the contribution of XCI to phenotype could potentially
impact prognosis for female carriers of X-linked retinal disease.
PMID- 26427429
TI - A Non-Canonical Role for beta-Secretase in the Retina.
AB - It has long been established that beta-Secretase (BACE) plays a critical role in
the formation of amyloid plaques in Alzheimer's Disease patients, but it is only
recently that the importance of beta-secretases in retinal pathophysiology has
been recognized. BACE expression is elevated in response to stress, and
downregulation results in lysosomal abnormalities and mitochondrial changes.
Inhibition of BACE can lead to reduced retinal function, retinal thinning,
lipofuscin accumulation and vascular dysfunction in mice. Furthermore, BACE
inhibition accelerates choroidal neovascularization (CNV) in mice. We propose
that BACE plays an important role in retinal homeostasis and that BACE
upregulation in response to stress is a protective measure.
PMID- 26427430
TI - The Consequences of Hypomorphic RPE65 for Rod and Cone Photoreceptors.
AB - RPE65 is essential for both rod- and cone-mediated vision. So far, more than 120
disease-associated mutations have been identified in the human RPE65 gene.
Differential clinical manifestations suggested that some patients suffer from
null mutations while others retain residual RPE65 activity and some useful
vision. To understand the mechanism of retinal degeneration or dysfunction caused
by such hypomorphic RPE65 alleles, we generated an Rpe65 (R91W) knock-in mouse
(R91W) that expresses a mutant RPE65 protein with reduced function. Data obtained
suggested that the R91W mouse is highly suitable to study the impact of RPE65
insufficiency on rod pathophysiology. To study the impact on cones, we combined
the R91W with the Nrl (-/-) mouse that develops an all-cone retina. Here we
summarize the consequences of hypomorphic RPE65 function (reduced 11-cis-retinal
synthesis) for rod and cone pathophysiology.
PMID- 26427431
TI - The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus
Autofluorescence, Retinal Senescence and Degeneration.
AB - One of the earliest events preceding several forms of retinal degeneration is the
formation and accumulation of vitamin A dimers in the retinal pigment epithelium
(RPE) and underlying Bruch's membrane (BM). Such degenerations include Stargardt
disease, Best disease, forms of retinitis pigmentosa, and age-related macular
degeneration (AMD). Since their discovery in the 1990's, dimers of vitamin A,
have been postulated as chemical triggers driving retinal senescence and
degeneration. There is evidence to suggest that the rate at which vitamin A
dimerizes and the eye's response to the dimerization products may dictate the
retina's lifespan. Here, we present outstanding questions, finding the answers to
which may help to elucidate the role of vitamin A dimerization in retinal
degeneration.
PMID- 26427432
TI - Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular
Degeneration, Stargardt Disease and Other Retinal Dystrophies?
AB - We discuss how an imperfect visual cycle results in the formation of vitamin A
dimers, thought to be involved in the pathogenesis of various retinal diseases,
and summarize how slowing vitamin A dimerization has been a therapeutic target of
interest to prevent blindness. To elucidate the molecular mechanism of vitamin A
dimerization, an alternative form of vitamin A, one that forms dimers more slowly
yet maneuvers effortlessly through the visual cycle, was developed. Such a
vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non
disruptive tool to understand the contribution of vitamin A dimers to vision
loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to
slow or stop vision loss associated with dry age-related macular degeneration
(AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers.
Human clinical trials of C20-D3-vitamin A (ALK-001) are underway.
PMID- 26427433
TI - Class I Phosphoinositide 3-Kinase Exerts a Differential Role on Cell Survival and
Cell Trafficking in Retina.
AB - Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that
phosphorylates the 3'OH of the inositol ring of phosphoinositides. They are
responsible for coordinating a diverse range of cell functions including
proliferation, cell survival, degranulation, vesicular trafficking, and cell
migration. The PI 3-kinases are grouped into three distinct classes: I, II, and
III. Class III PI3K has been shown to be involved in intracellular protein
trafficking, whereas class I PI3K is known to regulate cell survival following
activation of cell surface receptors. However, studies from our laboratory and
others have shown that class I PI3K may also be involved in photoreceptor protein
trafficking. Therefore, to learn more about the role of class I and class III
P13K in trafficking and to understand the impact of the lipid content of
trafficking cargo vesicles, we developed a methodology to isolate trafficking
vesicles from retinal tissue. PI3K class I and III proteins were enriched in our
extracted trafficking vesicle fraction. Moreover, levels of ether
phosphatidylethanolamine (PE) and ether phosphatidylcholine (PC) were
significantly higher in the trafficking vesicle fraction than in total retina.
These two lipid classes have been suggested to be involved with fusion/targeting
of trafficking vesicles.
PMID- 26427434
TI - Cell Cycle Proteins and Retinal Degeneration: Evidences of New Potential
Therapeutic Targets.
AB - During different forms of neurodegenerative diseases, including the retinal
degeneration, several cell cycle proteins are expressed in the dying neurons from
Drosophila to human revealing that these proteins are a hallmark of neuronal
degeneration. This is true for animal models of Alzheimer's, and Parkinson's
diseases, Amyotrophic Lateral Sclerosis and for Retinitis Pigmentosa as well as
for acute injuries such as stroke and light damage. Longitudinal investigation
and loss-of-function studies attest that cell cycle proteins participate to the
process of cell death although with different impacts, depending on the disease.
In the retina, inhibition of cell cycle protein action can result to massive
protection. Nonetheless, the dissection of the molecular mechanisms of neuronal
cell death is necessary to develop adapted therapeutic tools to efficiently
protect photoreceptors as well as other neuron types.
PMID- 26427435
TI - Nitric Oxide Synthase Activation as a Trigger of N-methyl-N-nitrosourea-Induced
Photoreceptor Cell Death.
AB - Retinal degeneration (RD) such as retinitis pigmentosa and age-related macular
degeneration are major causes of blindness in adulthood. As one of the model for
RD, intraperitoneal injection of N-methyl-N-nitrosourea (MNU) is widely used
because of its selective photoreceptor cell death. It has been reported that MNU
increases intracellular calcium ions in the retina and induces photoreceptor cell
death. Although calcium ion influx triggers the neuronal nitric oxide synthase
(nNOS) activation, the role of nNOS on photoreceptor cell death by MNU has not
been reported yet. In this study, we investigated the contribution of nNOS on
photoreceptor cell death induced by MNU in mice. MNU significantly increased NOS
activation at 3 day after treatment. Then, we evaluated the effect of nNOS
specific inhibitor, ethyl[4-(trifluoromethyl) phenyl]carbamimidothioate (ETPI) on
the MNU-induced photoreceptor cell death. At 3 days, ETPI clearly inhibited the
MNU-induced cell death in the ONL. These data indicate that nNOS is a key
molecule for pathogenesis of MNU-induced photoreceptor cell death.
PMID- 26427436
TI - Molecular Principles for Decoding Homeostasis Disruptions in the Retinal Pigment
Epithelium: Significance of Lipid Mediators to Retinal Degenerative Diseases.
AB - Dysregulated neuroinflammatory signaling during impending disruption of
homeostasis in retinal pigment epithelium (RPE) and photoreceptor cells (PRC)
takes place in early stages of retinal degeneration. PRCs avidly retain and
display the highest content in the human body of docosahexaenoic acid (DHA; an
omega-3 essential fatty acid). Docosanoids are DHA-derived mediators, such as
neuroprotectin D1 (NPD1), made on-demand that promote repair, phagocytic
clearance, cell survival, and are active participants of effective, well
concerted homeostasis restoration. Here we develop the concept that there is a
molecular logic that sustains PRC survival and that transcriptional signatures
governed by NPD1 in the RPE may be engaged.
PMID- 26427437
TI - Aging and Vision.
AB - Aging involves defined genetic, biochemical and cellular pathways that regulate
lifespan. These pathways are called longevity pathways and they have relevance
for many age-related diseases. In the eye, longevity pathways are involved in the
major blinding diseases, cataract, glaucoma, age-related macular degeneration
(AMD) and diabetic retinopathy. Pharmaceutical targeting of longevity pathways
can extend healthy lifespan in laboratory model systems. This offers the
possibility of therapeutic interventions to also delay onset or slow the
progression of age-related eye diseases. I suggest that retinal degeneration may
be viewed as accelerated aging of photoreceptors and that interventions extending
healthy lifespan may also slow the pace of photoreceptor loss.
PMID- 26427438
TI - The Potential Use of PGC-1alpha and PGC-1beta to Protect the Retina by
Stimulating Mitochondrial Repair.
AB - Damage to mitochondria is a common mechanism of cell death in inherited
neurodegenerative disorders. Therefore, mitochondrial protection and
mitochondrial repair are promising strategies to induce retinal neuroprotection.
Peroxisome proliferator-activated receptor gamma coactivator-alpha (PGC-1alpha)
and beta (PGC-1beta) are transcriptional coactivators that are the main
regulators of mitochondrial biogenesis. We propose that PGC-1alpha and PGC-1beta
could play a role in regulating retina cell survival, and may be important
therapeutic targets to prevent retinal degeneration.
PMID- 26427439
TI - Retinal Caveolin-1 Modulates Neuroprotective Signaling.
AB - Caveolin-1 (Cav-1), the scaffolding protein of caveolae, is expressed in several
retinal cell types and is associated with ocular pathologies. Cav-1 modulates
neuroinflammatory/neuroprotective responses to central nervous system injury. We
have shown that loss of Cav-1 results in a blunted cytokine response in retinas
challenged with inflammatory stimuli. As neuroinflammatory and neuroprotective
signaling overlap in their cytokine production and downstream signaling pathways,
we hypothesized that loss of Cav-1 may also suppress neuroprotective signaling in
the retina. To test this, we subjected mice in which Cav-1 was deleted
specifically in the retina to a neurodegenerative insult induced by sodium iodate
(NaIO3) and measured STAT3 activation, a measure of neuroprotective signaling.
Our results show that Cav-1 ablation blunts STAT3 activation induced by NaIO3.
STAT3 activation in response to intravitreal administration of the IL-6 family
cytokine, leukemia inhibitory factor (LIF), was not affected by Cav-1 deletion
indicating a competent gp130 receptor response. Thus, Cav-1 modulates
neuroprotective signaling by regulating the endogenous production of
neuroprotective factors.
PMID- 26427440
TI - Photoreceptor Neuroprotection: Regulation of Akt Activation Through
Serine/Threonine Phosphatases, PHLPP and PHLPPL.
AB - Serine/threonine kinase Akt is a downstream effector of insulin receptor/PI3K
pathway that is involved in many processes, including providing neuroprotection
to stressed rod photoreceptor cells. Akt signaling is known to be regulated by
the serine/threonine phosphatases, PHLPP (PH domain and leucine rich repeat
protein phosphatase) and PHLPPL (PH domain and leucine rich repeat protein
phosphatase-like). We previously reported that both phosphatases are expressed in
the retina, as well as in photoreceptor cells. In this study, we examined the
PHLPP and PHLPPL phosphatase activities towards non-physiological and
physiological substrates. Our results suggest that PHLPP was more active than
PHLPPL towards non-physiological substrates, whereas both PHLPP and PHLPP
dephosphorylated the physiological substrates of Akt1 and Akt3 with similar
efficiencies. Our results also suggest that knockdown of PHLPPL alone does not
increase Akt phosphorylation, due to a compensatory increase of PHLPP, which
results in the dephosphorylation of Akt. Therefore, PHLPP and PHLPPL regulate Akt
activation together when both phosphatases are expressed.
PMID- 26427441
TI - The Role of AMPK Pathway in Neuroprotection.
AB - Adenosine monophosphate-activated kinase (AMPK) is a highly conserved protein
kinase found in all eukaryotic genomes. It exists as heterotrimeric protein
consisting of alpha, beta, and gamma subunits. AMPK is activated by elevated
levels of adenosine mono-phosphate (AMP), which is produced during conditions of
low ATP production and perhaps mitochondrial dysfunction. Activation of AMPK has
been shown to regulate a large number of downstream pathways. These will either
increase energy production such as increase oxidation of fatty acids and glucose,
or decrease energy utilization such as inhibiting synthesis of glycogen, fatty
acid synthesis, and protein synthesis. In addition, being a key regulator of
physiological energy dynamics, AMPK has been demonstrated to play roles in
regulating various cellular processes such as mitochondrial biogenesis (Jager et
al. Proc Natl Acad Sci U S A 104:12017-12022, 2007), autophagy (Hyttinen et al.
Rejuven Res 14:651-660, 2011) and inflammation and immune responses (Giri et al.
2004). Retinal neurons have a high energy demand but have a poor energy storage
capacity. Because of this, it is likely that the AMPK signaling pathway plays an
important role in maintaining energy balance, and therefore may be a therapeutic
target to prevent or delay retinal degeneration.
PMID- 26427443
TI - Near-Infrared Photobiomodulation in Retinal Injury and Disease.
AB - Evidence is growing that exposure of tissue to low energy photon irradiation in
the far-red (FR) to near-infrared (NIR) range of the spectrum, collectively
termed "photobiomodulation" (PBM) can restore the function of damaged
mitochondria, upregulate the production of cytoprotective factors and prevent
apoptotic cell death. PBM has been applied clinically in the treatment of soft
tissue injuries and acceleration of wound healing for more than 40 years. Recent
studies have demonstrated that FR/NIR photons penetrate diseased tissues
including the retina. The therapeutic effects of PBM have been hypothesized to
result from intracellular signaling pathways triggered when FR/NIR photons are
absorbed by the mitochondrial photoacceptor molecule, cytochrome c oxidase,
culminating in improved mitochondrial energy metabolism, increased cytoprotective
factor production and cell survival. Investigations in rodent models of methanol
induced ocular toxicity, light damage, retinitis pigmentosa and age-related
macular degeneration have demonstrated the PBM attenuates photoreceptor cell
death, protects retinal function and exerts anti-inflammatory actions.
PMID- 26427442
TI - Tauroursodeoxycholic Acid Protects Retinal Function and Structure in rd1 Mice.
AB - We explored the potential protective effects of tauroursodeoxycholic acid (TUDCA)
on cone photoreceptor survival in a model of rapid retinal degeneration, the beta
Pde6 (rd1) (rd1) mouse model. We injected two strains of rd1 mice (B6.C3-Pde6b
(rd1) Hps4(le)/J and C57BL/6J-Pde6b (rd1-2)/J mice) daily from postnatal day (P)
6 to P21 with TUDCA or vehicle. At P21, retinal function was evaluated with light
adapted electroretinography (ERG) and retinal structure was observed with plastic
or frozen sections. TUDCA treatment partially preserved function and structure in
B6.C3-Pde6b (rd1) Hps4(le)/J mice but only partially preserved structure in
C57BL/6J-Pde6b (rd1-2)/J mice. Our results suggest a possible intervention for
patients undergoing rapid retinal degeneration.
PMID- 26427444
TI - Exercise and Cyclic Light Preconditioning Protect Against Light-Induced Retinal
Degeneration and Evoke Similar Gene Expression Patterns.
AB - To compare patterns of gene expression following preconditioning cyclic light
rearing versus preconditioning aerobic exercise. BALB/C mice were preconditioned
either by rearing in 800 lx 12:12 h cyclic light for 8 days or by running on
treadmills for 9 days, exposed to toxic levels of light to cause light-induced
retinal degeneration (LIRD), then sacrificed and retinal tissue harvested.
Subsets of mice were maintained for an additional 2 weeks and for assessment of
retinal function by electroretinogram (ERG). Both preconditioning protocols
partially but significantly preserved retinal function and morphology and induced
similar leukemia inhibitory factor (LIF) gene expression pattern. The data
demonstrate that exercise preconditioning and cyclic light preconditioning
protect photoreceptors against LIRD and evoke a similar pattern of retinal LIF
gene expression. It may be that similar stress response pathways mediate the
protection provided by the two preconditioning modalities.
PMID- 26427445
TI - Small Molecules that Protect Mitochondrial Function from Metabolic Stress
Decelerate Loss of Photoreceptor Cells in Murine Retinal Degeneration Models.
AB - One feature common to many of the pathways implicated in retinal degeneration is
increased metabolic stress leading to impaired mitochondrial function. We found
that exposure of cells to calcium ionophores or oxidants as metabolic stressors
diminish maximal mitochondrial capacity. A library of 50,000 structurally diverse
"drug-like" molecules was screened for protection against loss of calcium-induced
loss of mitochondrial capacity in 661W rod-derived cells and C6 glioblastomas.
Initial protective hits were then tested for protection against IBMX-induced loss
of mitochondrial capacity as measured via respirometry. Molecules that protected
mitochondria were then evaluated for protection of rod photoreceptor cells in
retinal explants from rd1 mice. Two of the molecules attenuated loss of
photoreceptor cells in the rd1 model. In the 661W cells, exposure to calcium
ionophore or tert-butylhydroperoxide caused mitochondrial fragmentation that was
blocked with the both compounds. Our studies have identified molecules that
protect mitochondria and attenuate loss of photoreceptors in models of retinal
degeneration suggesting that they could be good leads for development of
therapeutic drugs for treatment of a wide variety of retinal dystrophies.
PMID- 26427446
TI - Histone Deacetylase: Therapeutic Targets in Retinal Degeneration.
AB - Previous studies report that retinitis pigmentosa (RP) patients treated with the
histone deacetylase inhibitor (HDACi) valproic acid (VPA) present with improved
visual fields and delayed vision loss. However, other studies report poor
efficacy and safety of HDACi in other cohorts of retinal degeneration patients.
Furthermore, the molecular mechanisms by which HDACi can improve visual function
is unknown, albeit HDACi can attenuate pro-apoptotic stimuli and induce
expression of neuroprotective factors. Thus, further analysis of HDACi is
warranted in pre-clinical models of retinal degeneration including zebrafish.
Analysis of HDAC expression in developing zebrafish reveals diverse temporal
expression patterns during development and maturation of visual function.
PMID- 26427447
TI - Therapeutic Approach of Nanotechnology for Oxidative Stress Induced Ocular
Neurodegenerative Diseases.
AB - Oxidative stress plays a role in many different forms of neurodegenerative ocular
disease. The imbalance between the generation of endogenous reactive oxygen
species (ROS) and their corresponding neutralization by endogenous antioxidant
defense systems leads to cellular oxidative stress, oxidation of different bio
macromolecules, and eventually retinal disease. As a result, the administration
of supplemental endogenous antioxidant materials or exogenous ROS scavengers is
an interesting therapeutic approach for the treatment of forms of ocular disease
associated with oxidative stress. Thus far, different dietary antioxidant
supplements have been proven to be clinically reliable and effective, and
different antioxidant gene therapy approaches are under investigation. In
addition, various metal oxide nanoparticles were shown to be effective in
defending against oxidative stress-associated injury. These benefits are due to
free radical scavenging properties of the materials arising from non
stoichiometric crystal defects and oxygen deficiencies. Here we discuss the
application of this approach to the protection of the retina.
PMID- 26427448
TI - Transscleral Controlled Delivery of Geranylgeranylaceton Using a Polymeric Device
Protects Rat Retina Against Light Injury.
AB - We evaluated the effects of a transscleral drug delivery device, consisting of a
reservoir and controlled-release cover, which were made of photopolymerized
polyethylene glycol dimethacrylate and triethylene glycol dimethacrylate,
combined at different ratios. Geranylgeranylacetone (GGA), a heat-shock protein
(HSP) inducer, was loaded into the device. The GGA was released from the device
under zero-order kinetics. At both 1 week and 4 weeks after device implantation
on rat sclera, HSP70 gene and protein expression were up-regulated in the sclera
choroid-retinal pigment epithelium fraction of rat eyes treated with the GGA
loaded device compared with rat eyes treated with saline-loaded devices or eyes
of non-treated rats. Flash electroretinograms were recorded 4 days after white
light exposure (8000 lx for 18 h). Electroretinographic amplitudes of the a- and
b-waves were preserved significantly in rats treated with GGA-loaded devices
compared with rats treated with saline-loaded devices. Histological examination
showed that the outer nuclear layer thickness was preserved in rats that had the
GGA-loaded device. These results may show that transscleral GGA delivery using
our device may offer an alternative method to treat retinal diseases.
PMID- 26427449
TI - Targeting the Proteostasis Network in Rhodopsin Retinitis Pigmentosa.
AB - Mutations in rhodopsin are one of the most common causes of retinitis pigmentosa
(RP). Misfolding of rhodopsin can result in disruptions in cellular protein
homeostasis, or proteostasis. There is currently no available treatment for RP.
In this review, we discuss the different approaches currently being investigated
for treatment of rhodopsin RP, focusing on the potential of manipulation of the
proteostasis network as a therapeutic approach to combat retinal degeneration.
PMID- 26427451
TI - Tamoxifen-Containing Eye Drops Successfully Trigger Cre-Mediated Recombination in
the Entire Eye.
AB - Embryonic lethality in mice with targeted gene deletion is a major issue that can
be circumvented by using Cre-loxP-based animal models. Various inducible Cre
systems are available, e.g. such that are activated following tamoxifen
treatment, and allow deletion of a specific target gene at any desired time point
during the life span of the animal. In this study, we describe the efficiency of
topical tamoxifen administration by eye drops using a Cre- reporter mouse strain
(R26R). We report that tamoxifen-responsive CAGGCre-ER (TM) mice show a robust
Cre- mediated recombination throughout the entire eye.
PMID- 26427450
TI - Gene Therapy for MERTK-Associated Retinal Degenerations.
AB - MERTK-associated retinal degenerations are thought to have defects in
phagocytosis of shed outer segment membranes by the retinal pigment epithelium
(RPE), as do the rodent models of these diseases. We have subretinally injected
an RPE-specific AAV2 vector, AAV2-VMD2-hMERTK, to determine whether this would
provide long-term photoreceptor rescue in the RCS rat, which it did for up to 6.5
months, the longest time point examined. Moreover, we found phagosomes in the RPE
in the rescued regions of RCS retinas soon after the onset of light. The same
vector also had a major protective effect in Mertk-null mice, with a concomitant
increase in ERG response amplitudes in the vector-injected eyes. These findings
suggest that planned clinical trials with this vector will have a favorable
outcome.
PMID- 26427452
TI - Distinct Expression Patterns of AAV8 Vectors with Broadly Active Promoters from
Subretinal Injections of Neonatal Mouse Eyes at Two Different Ages.
AB - The retinal expression patterns were analyzed following the injection of serotype
8 adeno-associated virus (AAV8) vectors that utilize two broadly active and
commonly used sets of transcription regulatory sequences. These include the human
cytomegalovirus (CMV) immediate early (IE) enhancer/promoter and the hybrid CAG
element (also known as CAGGS or CBA) composed of a partial human CMV IE enhancer
and the chicken beta-actin promoter and intron. Subretinal delivery to postnatal
day 0 (P0) or 6 (P6) mouse eyes resulted in efficient labeling of retinal cells,
but with very distinct patterns. With P0 delivery, AAV8-CMV-GFP selectively
labelled photoreceptors, while AAV8-CAG-GFP efficiently labeled both outer and
inner retinal neurons, including photoreceptors, horizontal cells, amacrine cells
and retinal ganglion cells. With P6 delivery, both vectors led to efficient
labeling of photoreceptors and Muller glia cells, but not of inner retinal
neurons. Our results suggest that the cell types that express the genes encoded
by subretinally delivered AAV8 vectors are determined by both the timing of the
injection and the regulatory sequences.
PMID- 26427453
TI - Characterization of Ribozymes Targeting a Congenital Night Blindness Mutation in
Rhodopsin Mutation.
AB - The G90D mutation in the rhodopsin gene leads to autosomal dominant congenital
stationary night blindness (CSNB) in patients. This occurs because the G90D
mutant protein cannot efficiently bind chromophore and is constitutively active.
To combat this mutation, we designed and characterized two different hammerhead
ribozymes to cleave G90D transcript. In vitro testing showed that the G90D1
ribozyme efficiently and specifically cleaved the mutant transcript while G90D2
cleaved both WT and mutant transcript. AAV-mediated delivery of G90D1 under the
control of the mouse opsin promoter (MOP500) to G90D transgenic eyes showed that
the ribozyme partially retarded the functional degeneration (as measured by
electroretinography [ERG]) associated with this mutation. These results suggest
that with additional optimization, ribozymes may be a useful part of the gene
therapy knockdown strategy for dominant retinal disease.
PMID- 26427454
TI - Antisense Oligonucleotide Therapy for Inherited Retinal Dystrophies.
AB - Inherited retinal dystrophies (IRDs) are an extremely heterogeneous group of
genetic diseases for which currently no effective treatment strategies exist.
Over the last decade, significant progress has been made utilizing gene
augmentation therapy for a few genetic subtypes of IRD, although several
technical challenges so far prevent a broad clinical application of this approach
for other forms of IRD. Many of the mutations leading to these retinal diseases
affect pre-mRNA splicing of the mutated genes . Antisense oligonucleotide (AON)
mediated splice modulation appears to be a powerful approach to correct the
consequences of such mutations at the pre-mRNA level , as demonstrated by
promising results in clinical trials for several inherited disorders like
Duchenne muscular dystrophy, hypercholesterolemia and various types of cancer. In
this mini-review, we summarize ongoing pre-clinical research on AON-based therapy
for a few genetic subtypes of IRD , speculate on other potential therapeutic
targets, and discuss the opportunities and challenges that lie ahead to translate
splice modulation therapy for retinal disorders to the clinic.
PMID- 26427455
TI - Functional Rescue of Retinal Degeneration-Associated Mutant RPE65 Proteins.
AB - More than 100 different mutations in the RPE65 gene are associated with inherited
retinal degeneration. Although some missense mutations have been shown to abolish
isomerase activity of RPE65, the molecular bases leading to loss of function and
retinal degeneration remain incompletely understood. Here we show that several
missense mutations resulted in significant decrease in expression level of RPE65
in the human retinal pigment epithelium cells. The 26S proteasome non-ATPase
regulatory subunit 13, a newly identified negative regulator of RPE65, mediated
degradation of mutant RPE65s, which were misfolded and formed aggregates in the
cells. Many mutations, including L22P, T101I, and L408P, were mapped on nonactive
sites of RPE65. Enzyme activities of these mutant RPE65s were significantly
rescued at low temperature, whereas mutant RPE65s with a distinct active site
mutation could not be rescued under the same conditions. 4-phenylbutyrate (PBA)
displayed a significant synergistic effect on the low temperature-mediated rescue
of the mutant RPE65s. Our results suggest that a low temperature eye mask and
PBA, a FDA-approved oral medicine, may provide a promising "protein repair
therapy" that can enhance the efficacy of gene therapy for delaying retinal
degeneration caused by RPE65 mutations.
PMID- 26427456
TI - Evaluation of Ocular Gene Therapy in an Italian Patient Affected by Congenital
Leber Amaurosis Type 2 Treated in Both Eyes.
AB - Gene therapy clinical trials with gene augmentation therapy for Leber Congenital
Amaurosis have shown partial reversal of retinal dysfunction. Most studies
described the effect of treatment in a single eye and limited evidence is
reported in literature about patients treated in both eyes. In this chapter, we
present the findings of a young patient treated in both eyes. Efficacy of the
treatment was assessed with Best Corrected Visual Acuity, Goldman Visual Field
testing, Esterman computerized binocular visual field and Microperimetric
testing. Post-treatment results showed improvement of visual function in both
eyes, in particular, a strong amelioration was observed after the first
injection, by using conventional monocular tests. Moreover, the treatment in the
second eye resulted in a further improvement of binocular visual functionality,
as easily detected by computerized binocular visual field. In conclusion, our
data suggest that gene therapy can inhibit retinal degeneration and can be safe
and effective in restoring visual functionality in young subjects treated in both
eyes. Finally, new outcome measurements, in particular binocular computerized
visual field parameters, can therefore be useful to quantify overall visual gain
in patients undergoing gene therapy in both eyes.
PMID- 26427457
TI - Regenerative Medicine: Solution in Sight.
AB - The retina, like other central nervous system tissues, has poor regenerative
properties in humans. Therefore, diseases that cause retinal cell loss, such as
Age-related macular degeneration (AMD), retinitis pigmentosa (RP), Leber
congenital amaurosis, Usher syndrome, glaucoma, and diabetic retinopathy,
typically result in permanent visual impairment. Stem cell technologies have
revolutionized our ability to produce neural cells in abundant supply. Much stem
cell research effort is focused on producing the required cell types for cell
replacement, or to generate disease-in-a-dish models to elucidate novel disease
mechanisms for therapeutic development. Here we review the recent advances in
stem cell studies relevant to producing RPE and retinal cells, and highlight
future directions.
PMID- 26427458
TI - Personalized Medicine: Cell and Gene Therapy Based on Patient-Specific iPSC
Derived Retinal Pigment Epithelium Cells.
AB - Interest in generating human induced pluripotent stem (iPS) cells for stem cell
modeling of diseases has overtaken that of patient-specific human embryonic stem
cells due to the ethical, technical, and political concerns associated with the
latter. In ophthalmology, researchers are currently using iPS cells to explore
various applications, including: (1) modeling of retinal diseases using patient
specific iPS cells; (2) autologous transplantation of differentiated retinal
cells that undergo gene correction at the iPS cell stage via gene editing tools
(e.g., CRISPR/Cas9, TALENs and ZFNs); and (3) autologous transplantation of
patient-specific iPS-derived retinal cells treated with gene therapy. In this
review, we will discuss the uses of patient-specific iPS cells for
differentiating into retinal pigment epithelium (RPE) cells, uncovering disease
pathophysiology, and developing new treatments such as gene therapy and cell
replacement therapy via autologous transplantation.
PMID- 26427459
TI - Human Retinal Pigment Epithelium Stem Cell (RPESC).
AB - The retinal pigment epithelium (RPE) is a pigmented cellular monolayer that
supports photoreceptor cells located in the overlying neural retina. The RPE is
critical for vision and its dysfunction results in numerous pathologies, several
with limited available disease-altering strategies. Regeneration of the retina
from RPE is robust in lower vertebrates, but is not normally exhibited in
mammals. We recently found that a subpopulation of human RPE cells can be
stimulated in culture to generate multipotent self-renewing cells-the RPE stem
cell (RPESC). RPESC can be expanded to generate RPE progeny that are a potential
source for cell replacement therapy. Alternatively, RPESC can produce mesenchymal
progeny which serve as a disease model of epiretinal membrane formation. Yet
another potential application of RPESCs is activation within the eye to awaken
dormant endogenous repair.
PMID- 26427460
TI - Embryonic Stem Cell-Derived Microvesicles: Could They be Used for Retinal
Regeneration?
AB - Mouse embryonic stem cells (mESCs) release into the medium in which they are
cultured heterogeneous populations of microvesicles (mESMVs), important
components of cell-cell communication, that transfer their contents not only to
other stem cells but also to cells of other origins. The purpose of these studies
was to demonstrate that ESMVs could be the signals that lead the retinal
progenitor Muller cells to de-differentiate and re-entry the cell cycle, followed
by differentiation along retinal lineages. Indeed, we found that ESMVs induce
these processes and change Muller cells' microenvironment towards a more
permissive state for tissue regeneration.
PMID- 26427461
TI - Intravitreal Implantation of Genetically Modified Autologous Bone Marrow-Derived
Stem Cells for Treating Retinal Disorders.
AB - A number of retinal degenerative diseases may be amenable to treatment with
continuous intraocular delivery of therapeutic agents that cannot be delivered
effectively to the retina via systemic or topical administration. Among these
disorders are lysosomal storage diseases resulting from deficiencies in soluble
lysosomal enzymes. Most cells, including those of the retina, are able to take up
these enzymes and incorporate them in active form into their lysosomes. In
theory, therefore, continuous intraocular administration of a normal form of a
soluble lysosomal enzyme should be able to cure the molecular defect in the
retinas of subjects lacking this enzyme. Experiments were conducted to determine
whether genetically modified bone marrow-derived stem cells implanted into the
vitreous could be used as -vehicles for continuous delivery of such enzymes to
the retina. Bone marrow-derived mesenchymal stem cells (MSCs) from normal mice
were implanted into the vitreous of mice undergoing retinal degeneration as a
result of a mutation in the PPT1 gene. The implanted cells appeared to survive
indefinitely in the vitreous without proliferating or invading the retina. This
indicates that intravitreal implantation of MSCs is likely a safe means of long
term delivery of proteins synthesized by the implanted cells. Experiments have
been initiated to test the efficacy of using genetically modified autologous MSCs
to inhibit retinal degeneration in a canine model of neuronal ceroid
lipofuscinosis.
PMID- 26427462
TI - Gliosis Can Impede Integration Following Photoreceptor Transplantation into the
Diseased Retina.
AB - Retinal degenerations leading to the loss of photoreceptor (PR) cells are a major
cause of vision impairment and untreatable blindness. There are few clinical
treatments and none can reverse the loss of vision. With the rapid advances in
stem cell biology and techniques in cell transplantation, PR replacement by
transplantation represents a broad treatment strategy applicable to many types of
degeneration. The number of donor cells that integrate into the recipient retina
determines transplantation success, yet the degenerating retinae presents a
number of barriers that can impede effective integration. Here, we briefly review
recent advances in the field of PR transplantation. We then describe how
different aspects of gliosis may impact on cell integration efficiency.
PMID- 26427463
TI - Interkinetic Nuclear Migration in the Regenerating Retina.
AB - In the adult zebrafish, death of retinal neurons stimulates Muller glia to re
enter the cell cycle to produce neuronal progenitor cells (NPCs) that undergo
further cell divisions and differentiate to replace lost neurons in the correct
spatial locations. Understanding the mechanisms regulating retinal regeneration
will ultimately provide avenues to overcome vision loss in human. Recently, the
observation of interkinetic nuclear migration (INM) of Muller glia in the
regenerating zebrafish retina resulted in the inclusion of an additional complex
step to the regeneration process. The pathways regulating INM and its function in
the regenerating retina have not been well studied. Here, we summarize the
evidence for INM in the regenerating retina and review mechanisms that control
INM during neuro-epithelial development in the context of pathways known to be
critical during retinal regeneration.
PMID- 26427464
TI - Use of a Machine Learning-Based High Content Analysis Approach to Identify
Photoreceptor Neurite Promoting Molecules.
AB - High content analysis (HCA) has become a leading methodology in phenotypic drug
discovery efforts. Typical HCA workflows include imaging cells using an automated
microscope and analyzing the data using algorithms designed to quantify one or
more specific phenotypes of interest. Due to the richness of high content data,
unappreciated phenotypic changes may be discovered in existing image sets using
interactive machine-learning based software systems. Primary postnatal day four
retinal cells from the photoreceptor (PR) labeled QRX-EGFP reporter mice were
isolated, seeded, treated with a set of 234 profiled kinase inhibitors and then
cultured for 1 week. The cells were imaged with an Acumen plate-based laser
cytometer to determine the number and intensity of GFP-expressing, i.e. PR,
cells. Wells displaying intensities and counts above threshold values of interest
were re-imaged at a higher resolution with an INCell2000 automated microscope.
The images were analyzed with an open source HCA analysis tool, PhenoRipper
(Rajaram et al., Nat Methods 9:635-637, 2012), to identify the high GFP-inducing
treatments that additionally resulted in diverse phenotypes compared to the
vehicle control samples. The pyrimidinopyrimidone kinase inhibitor CHEMBL
1766490, a pan kinase inhibitor whose major known targets are p38alpha and the
Src family member lck, was identified as an inducer of photoreceptor
neuritogenesis by using the open-source HCA program PhenoRipper. This finding was
corroborated using a cell-based method of image analysis that measures
quantitative differences in the mean neurite length in GFP expressing cells.
Interacting with data using machine learning algorithms may complement
traditional HCA approaches by leading to the discovery of small molecule-induced
cellular phenotypes in addition to those upon which the investigator is initially
focusing.
PMID- 26427465
TI - A Novel Approach to Identify Photoreceptor Compartment-Specific Tulp1 Binding
Partners.
AB - Photoreceptors (PRs) are highly polarized and compartmentalized cells with large
amounts of proteins synthesized in the inner segment (IS) and transported to the
outer segment (OS) and synaptic terminal. The PR-specific protein, Tulp1, is
localized to the IS and synapse and is hypothesized to be involved in protein
trafficking. To better understand the molecular processes that regulate protein
trafficking in PRs, we aimed to identify compartment-specific Tulp1 binding
partners. Serial tangential sectioning of Long Evans rat retinas was utilized to
isolate the IS and synaptic PR compartments. Tulp1 binding partners in each of
these layers were identified using co-immunoprecipitation (co-IP) with Tulp1
antibodies. The co-IP eluates were separated by SDS-PAGE, trypsinized into
peptide fragments, and proteins were identified by liquid chromatography tandem
mass spectrometry. In the IS, potential Tulp1-binding partners included
cytoskeletal scaffold proteins, protein trafficking molecules, as well as members
of the phototransduction cascade. In the synaptic region, the majority of
interacting proteins identified were cytoskeletal. A separate subset of proteins
were identified in both the IS and synapse including chaperones and family
members of the GTPase activating proteins. Tulp1 has two distinct PR compartment
specific interactomes. Our results support the hypothesis that Tulp1 is involved
in the trafficking of proteins from the IS to the OS and the continuous membrane
remodeling and vesicle cycling at the synaptic terminal.
PMID- 26427466
TI - Thyroid Hormone Signaling and Cone Photoreceptor Viability.
AB - Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and
apoptosis. In the retina, TH signaling plays a central role in cone opsin
expression. TH signaling inhibits S opsin expression, stimulates M opsin
expression, and promotes dorsal-ventral opsin patterning. TH signaling has also
been associated with cone photoreceptor viability. Treatment with thyroid hormone
triiodothyronine (T3) or induction of high T3 by deleting the hormone
inactivating enzyme type 3 iodothyronine deiodinase (DIO3) causes cone death in
mice. This effect is reversed by deletion of the TH receptor (TR) gene.
Consistent with the T3 treatment effect, suppressing TH signaling preserves cones
in mouse models of retinal degeneration. The regulation of cone survival by TH
signaling appears to be independent of its regulatory role in cone opsin
expression. The mechanism by which TH signaling regulates cone viability remains
to be identified. The current understanding of TH signaling regulation in
photoreceptor viability suggests that suppressing TH signaling locally in the
retina may represent a novel strategy for retinal degeneration management.
PMID- 26427467
TI - In-Depth Functional Diagnostics of Mouse Models by Single-Flash and Flicker
Electroretinograms without Adapting Background Illumination.
AB - Electroretinograms (ERGs) are commonly recorded at the cornea for an assessment
of the functional status of the retina in mouse models. Full-field ERGs can be
elicited by single-flash as well as flicker light stimulation although in most
laboratories flicker ERGs are recorded much less frequently than singleflash
ERGs. Whereas conventional single-flash ERGs contain information about layers,
i.e., outer and inner retina, flicker ERGs permit functional assessment of the
vertical pathways of the retina, i.e., rod system, cone ON-pathway, and cone OFF
pathway, when the responses are evoked at a relatively high luminance (0.5 log cd
s/m(2)) with varying frequency (from 0.5 to 30 Hz) without any adapting
background illumination. Therefore, both types of ERGs complement an in-depth
functional characterization of the mouse retina, allowing for a discrimination of
an underlying functional pathology. Here, we introduce the systematic
interpretation of the single-flash and flicker ERGs by demonstrating several
different patterns of functional phenotype in genetic mouse models, in which
photoreceptors and/or bipolar cells are primarily or secondarily affected.
PMID- 26427468
TI - The Role of Intraflagellar Transport in the Photoreceptor Sensory Cilium.
AB - The photoreceptor is a complex specialized cell in which a major component
responsible for visual transduction is the photoreceptor sensory cilium (PSC).
Building and maintenance of the PSC requires the transport of large proteins
along microtubules that extend from the inner segments to the outer segments. A
key process, termed intraflagellar transport (IFT), has been recognized as an
essential phenomenon for photoreceptor development and maintenance, and exciting
new studies have highlighted its importance in retinal and cilia related
diseases. This review focuses on the important roles of IFT players, including
motor proteins, IFT proteins, and photoreceptor-specific cargos in photoreceptor
sensory cilium. In addition, specific IFT components that are involved in
inherited human diseases are discussed.
PMID- 26427469
TI - Regulation of Retinal Development via the Epigenetic Modification of Histone H3.
AB - We are interested in the roles of epigenetic mechanisms in retinal development.
By ChIP-qPCR using whole retinal extracts at various developmental stages, we
found that the levels of methylation of histones H3K27 and H3K4 and acetylation
of histone H3 at specific loci in various genes, which play critical roles in
retinal proliferation and differentiation, changed dramatically during retinal
development. We next focused on the roles of H3K27 trimethylation in retinal
development. Ezh1 and Ezh2 are methyltransferases that act on H3K27, while Jmjd3
and Utx are demethylases. We found that Ezh2 and Jmjd3 were mainly expressed
during retinal development, and a loss-of-function of these genes revealed a role
for H3K27me3 in the maturation of subsets of bipolar cells. Furthermore, Ezh2 and
Jmjd3 regulate H3K27 trimethylation at specific loci within Bhlhb4 and Vsx1,
which play critical roles in the differentiation of subsets of bipolar cells. Utx
is expressed weakly in retina, and the down-regulation of Utx by sh-RNA in
retinal explants suggested that Utx also participates in the maturation of
bipolar cells. Ezh1 is expressed weakly in postnatal retina, and the phenotype of
Ezh2-knockout retina suggested that Ezh1 plays a role in the methylation of H3K27
in the late phase of retinal differentiation. Taken together, we found that these
four genes, which exhibit temporally and spatially unique expression patterns
during retinal development, play critical roles in the differentiation of retinal
subsets through the regulation of histone H3K27 methylation at critical genetic
loci.
PMID- 26427470
TI - The Potential Role of Flavins and Retbindin in Retinal Function and Homeostasis.
AB - Flavins are highly concentrated in the retina; likely because they are involved
as cofactors in energy metabolism and photoreceptors have an extremely high
metabolic rate. How this concentration is established is currently unknown, but
photoreceptor specific proteins may exist that shuttle flavins to flavoproteins,
which may also function in retinal neuron specific processes. It has been
suggested due to sequence homology to folate receptors that retbindin could be
binding flavins in the retina. Here we present a brief overview of flavins in the
retina and initial findings that suggest retbindin may be located in the
photoreceptor layer where flavin acquisition from the RPE would occur.
PMID- 26427471
TI - Identification of Tyrosine O Sulfated Proteins in Cow Retina and the 661W Cell
Line.
AB - Lack of tyrosine O Sulfation compromises both rod and cone electroretinographic
responses emphasizing the importance of this post-translational modification for
vision. To identify tyrosine sulfated proteins in retina, cow retinal lysates
were subjected to immunoaffinity purification using an anti-sulfotyrosine
antibody. The tyrosine sulfated proteins were eluted from the column using a
sulfotyrosine pentapeptide and identified using mass spectrometry. Similarly,
tyrosine sulfated proteins secreted by the 661W cell line were identified.
Proteins identified were vitronectin, fibronectin, fibulin 2, nidogen, collagen V
alpha 2, complement component 3 and C4 and fibrinogen beta. All proteins were
subjected to analysis by 'Sulfinator' to determine potential sulfated tyrosines.
PMID- 26427472
TI - The Function of Arf-like Proteins ARL2 and ARL3 in Photoreceptors.
AB - Arf-like proteins (ARLs) are ubiquitously expressed small G proteins of the RAS
superfamily. In photoreceptors, ARL2 and ARL3 participate in the trafficking of
lipidated membrane-associated proteins and colocalize in the inner segment with
UNC119A and PDEdelta. UNC119A and PDEdelta are acyl- and prenyl-binding proteins,
respectively, involved in trafficking of acylated (transducin-alpha subunit,
nephrocystin NPHP3) and prenylated proteins (GRK1, PDE6). Germline Arl3 knockout
mice do not survive beyond postnatal day 21 and display ciliary defects in
multiple organs (kidney, liver and pancreas) as well as retinal degeneration.
Conditional knockouts will be necessary to delineate mechanisms of protein
transport in retina disease.
PMID- 26427473
TI - Characterization of Antibodies to Identify Cellular Expression of Dopamine
Receptor 4.
AB - The dopamine receptor D4 (DRD4) plays an important role in vision. In order to
study the DRD4 expression in vivo, it is important to have antibodies that are
specific for DRD4 for both immunoblot and immunohistochemical (IHC) applications.
In this study, six antibodies raised against DRD4 peptides were tested in vitro,
using transfected mammalian cells, and in vivo, using mouse retinas. Three Santa
Cruz (SC) antibodies, D-16, N-20, and R-20, were successful in IHC of transfected
DRD4; however, N-20 was the only one effective on immunoblot analysis in DRD4
transfected cells and IHC of mouse retinal sections, while R-20, 2B9, and
Antibody Verify AAS63631C were non-specific or below detection.
PMID- 26427474
TI - A Possible Role of Neuroglobin in the Retina After Optic Nerve Injury: A
Comparative Study of Zebrafish and Mouse Retina.
AB - Neuroglobin (Ngb) is a new member of the family of heme proteins and is
specifically expressed in neurons of the central and peripheral nervous systems
in all vertebrates. In particular, the retina has a 100-fold higher concentration
of Ngb than do other nervous tissues. The role of Ngb in the retina is yet to be
clarified. Therefore, to understand the functional role of Ngb in the retina
after optic nerve injury (ONI), we used two types of retina, from zebrafish and
mice, which have permissible and non-permissible capacity for nerve regeneration
after ONI, respectively. After ONI, the Ngb protein in zebrafish was upregulated
in the amacrine cells within 3 days, whereas in the mouse retina, Ngb was
downregulated in the retinal ganglion cells (RGCs) within 3 days. Zebrafish Ngb
(z-Ngb) significantly enhanced neurite outgrowth in retinal explant culture.
According to these results, we designed an overexpression experiment with the
mouse Ngb (m-Ngb) gene in RGC-5 cells (retinal precursor cells). The excess of m
Ngb actually rescued RGC-5 cells under hypoxic conditions and significantly
enhanced neurite outgrowth in cell culture. These data suggest that mammalian Ngb
has positive neuroprotective and neuritogenic effects that induce nerve
regeneration after ONI.
PMID- 26427475
TI - JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In
Vivo and after Hypoxia In Vitro.
AB - Mitogen-activated protein kinases (MAPKs) are key regulators that have been
linked to cell survival and death. Among the main classes of MAPKs, c-jun N
terminal kinase (JNK) has been shown to mediate cell stress responses associated
with apoptosis. In Vitro, hypoxia induced a significant increase in 661W cell
death that paralleled increased activity of JNK and c-jun. 661W cells cultured in
presence of the inhibitor of JNK (D-JNKi) were less sensitive to hypoxia-induced
cell death. In vivo, elevation in intraocular pressure (IOP) in the rat promoted
cell death that correlated with modulation of JNK activation. In vivo inhibition
of JNK activation with D-JNKi resulted in a significant and sustained decrease in
apoptosis in the ganglion cell layer, the inner nuclear layer and the
photoreceptor layer. These results highlight the protective effect of D-JNKi in
ischemia/reperfusion induced cell death of the retina.
PMID- 26427476
TI - Cell Fate of Muller Cells During Photoreceptor Regeneration in an N-Methyl-N
nitrosourea-Induced Retinal Degeneration Model of Zebrafish.
AB - Zebrafish can regenerate several organs such as the tail fin, heart, central
nervous system, and photoreceptors. Very recently, a study has demonstrated the
photoreceptor regeneration in the alkylating agent N-methyl-N-nitrosourea (MNU)
induced retinal degeneration (RD) zebrafish model, in which whole photoreceptors
are lost within a week after MNU treatment and then regenerated within a month.
The research has also shown massive proliferation of Muller cells within a week.
To address the question of whether proliferating Muller cells are the source of
regenerating photoreceptors, which remains unknown in the MNU-induced zebrafish
RD model, we employed a BrdU pulse-chase technique to label the proliferating
cells within a week after MNU treatment. As a result of the BrdU pulse-chase
technique, a number of BrdU(+) cells were observed in the outer nuclear layer as
well as the inner nuclear layer. This implies that regenerating photoreceptors
are derived from proliferating Muller cells in the zebrafish MNU-induced RD
model.
PMID- 26427477
TI - Polymodal Sensory Integration in Retinal Ganglion Cells.
AB - An animal's ability to perceive the external world is conditioned by its capacity
to extract and encode specific features of the visual image. The output of the
vertebrate retina is not a simple representation of the 2D visual map generated
by photon absorptions in the photoreceptor layer. Rather, spatial, temporal,
direction selectivity and color "dimensions" of the original image are
distributed in the form of parallel output channels mediated by distinct retinal
ganglion cell (RGC) populations. We propose that visual information transmitted
to the brain includes additional, light-independent, inputs that reflect the
functional states of the retina, anterior eye and the body. These may include the
local ion microenvironment, glial metabolism and systemic parameters such as
intraocular pressure, temperature and immune activation which act on ion channels
that are intrinsic to RGCs. We particularly focus on light-independent mechanical
inputs that are associated with physical impact, cell swelling and intraocular
pressure as excessive mechanical stimuli lead to the counterintuitive experience
of "pressure phosphenes" and/or debilitating blinding disease such as glaucoma
and diabetic retinopathy. We point at recently discovered retinal
mechanosensitive ion channels as examples through which molecular physiology
brings together Greek phenomenology, modern neuroscience and medicine. Thus, RGC
output represents a unified picture of the embodied context within which vision
takes place.
PMID- 26427478
TI - Pigment Epithelium-Derived Factor, a Protective Factor for Photoreceptors in
Vivo.
AB - Pigment epithelium-derived factor (PEDF) is a natural protein of the retina with
demonstrable neurotrophic properties, found in the interphotoreceptor matrix in
intimate contact with photoreceptors. This review summarizes the effects of PEDF
on photoreceptors in several animal models of retinal degeneration.
PMID- 26427479
TI - The mTOR Kinase Inhibitor INK128 Blunts Migration of Cultured Retinal Pigment
Epithelial Cells.
AB - Retinal pigment epithelium (RPE) cell migration in response to disease has been
reported for age-related macular degeneration, proliferative vitreoretinopathy,
and proliferative diabetic retinopathy. The complex molecular process of RPE cell
migration is regulated in part by growth factors and cytokines, and activation of
the PI3/AKT/mTOR signaling pathway. Rapamycin, an allosteric mTOR inhibitor, has
been shown to block only one of the primary downstream mTOR effectors, p70 S6
kinase 1, in many cell types. INK128, a selective mTOR ATP binding site
competitor, blocks both p70 S6 kinase 1 and a second primary downstream effector,
4E-BP1. We performed scratch assays using differentiated ARPE-19 and primary
porcine RPE cells to assess the effect of mTOR inhibition on cell migration. We
found that INK128-mediated blocking of both p70 S6 kinase 1 and 4E-BP1 was much
more effective at preventing RPE cell migration than rapamycin-mediated
inhibition of p70 S6 kinase 1 alone.
PMID- 26427480
TI - Live Imaging of LysoTracker-Labelled Phagolysosomes Tracks Diurnal Phagocytosis
of Photoreceptor Outer Segment Fragments in Rat RPE Tissue Ex Vivo.
AB - Renewal of rod photoreceptor outer segments in the mammalian eye involves
synchronized diurnal shedding after light onset of spent distal outer segment
fragments (POS) linked to swift clearance of shed POS from the subretinal space
by the adjacent retinal pigment epithelium (RPE). Engulfed POS phagosomes in RPE
cells mature to acidified phagolysosomes, which accomplish enzymatic degradation
of POS macromolecules. Here, we used an acidophilic fluorophore LysoTracker to
label acidic organelles in freshly dissected, live rat RPE tissue flat mounts. We
observed that all RPE cells imaged contained numerous acidified POS
phagolysosomes whose abundance per cell was dramatically increased 2 h after
light onset as compared to either 1 h before or 4 h after light onset. Lack of
organelles of similar diameter (of 1-2 MUm) in phagocytosis-defective mutant RCS
rat RPE confirmed that LysoTracker live imaging detected POS phagolysosomes. Lack
of increase in lysosomal membrane protein LAMP-1 in RPE/choroid during the
diurnal phagocytic burst suggests that formation of POS phagolysosomes in RPE in
situ may not involve extra lysosome membrane biogenesis. Taken together, we
report a new imaging approach that directly detects POS phagosome acidification
and allows rapid tracking and quantification of POS phagocytosis by live RPE
tissue ex situ.
PMID- 26427481
TI - Cre Recombinase: You Can't Live with It, and You Can't Live Without It.
AB - The development of conditional gene targeting has greatly advanced our knowledge
of human retinal diseases, but issues have arisen related to the use of some Cre
expressing mouse lines. In this article, we discuss potential problems associated
with transgenic Cre expression-induced degeneration and alteration of rod
photoreceptors and retinal pigment epithelium (RPE). Our strategy for
circumventing RPE degeneration by induced transient Cre expression uses a single
intravitreal doxycycline injection in a tetracycline-inducible RPE-specific Cre
mouse line, which results in productive Cre-mediated recombination efficiently in
the RPE. As constitutive expression of Cre in the RPE alters RPE biology, this
inducible Cre/lox system provides an opportunity for conditional gene targeting
in the RPE, a tissue that is closely related to photoreceptor degeneration, age
related macular degeneration, and diabetic retinopathy.
PMID- 26427482
TI - Efficiency of Membrane Protein Expression Following Infection with Recombinant
Adenovirus of Polarized Non-Transformed Human Retinal Pigment Epithelial Cells.
AB - Transient expression of exogenous proteins facilitates studies of molecular
mechanisms and utility for transplantation of retinal pigment epithelial (RPE)
cells in culture. Here, we compared expression of the membrane protein beta5
integrin-GFP (beta5-GFP) in two recently established models of differentiated
human RPE, adult RPE stem cell-derived RPE and primary fetal RPE, upon infection
with recombinant adenovirus or transfection with DNA in liposomes. We varied
viral titer and duration of virus incubation and examined beta5-GFP and the tight
junction marker ZO-1 in manipulated cells by confocal microscopy. Fewer than 5 %
of cells expressed beta5-GFP after liposome-mediated transfection. The percentage
of cells with detectable beta5-GFP exceeded 90 % after adenovirus infection for
as little as 1 h. Decreasing virus titer two-fold did not alter the fraction of
cells expressing beta5-GFP but increased variability of beta5-GFP level among
cells. In cells with low expression levels, beta5-GFP localized mostly to the
apical plasma membrane like endogenous alphavbeta5 integrin. In cells with high
expression levels, beta5-GFP localized to the cytoplasm in addition to the apical
surface suggesting accumulation in trafficking compartments. Altogether,
adenovirus delivery yields efficient exogenous membrane protein expression of
correct polarity in differentiated human RPE cells in culture.
PMID- 26427484
TI - Lysosomal Trafficking Regulator (LYST).
AB - Regulation of vesicle trafficking to lysosomes and lysosome-related organelles
(LROs) as well as regulation of the size of these organelles are critical to
maintain their functions. Disruption of the lysosomal trafficking regulator
(LYST) results in Chediak-Higashi syndrome (CHS), a rare autosomal recessive
disorder characterized by oculocutaneous albinism, prolonged bleeding, severe
immunodeficiency, recurrent bacterial infection, neurologic dysfunction and
hemophagocytic lympohistiocytosis (HLH). The classic diagnostic feature of the
syndrome is enlarged LROs in all cell types, including lysosomes, melanosomes,
cytolytic granules and platelet dense bodies. The most striking CHS ocular
pathology observed is an enlargement of melanosomes in the retinal pigment
epithelium (RPE), which leads to aberrant distribution of eye pigmentation, and
results in photophobia and decreased visual acuity. Understanding the molecular
function of LYST and identification of its interacting partners may provide
therapeutic targets for CHS and other diseases associated with the regulation of
LRO size and/or vesicle trafficking, such as asthma, urticaria and Leishmania
amazonensis infections.
PMID- 26427483
TI - Contribution of Ion Channels in Calcium Signaling Regulating Phagocytosis: MaxiK,
Cav1.3 and Bestrophin-1.
AB - Mutations in the BEST1 gene lead to a variety of retinal degenerations including
Best's vitelliforme macular degeneration. The BEST1 gene product, bestrophin-1,
is expressed in the retinal pigment epithelium (RPE). It is likely that mutant
bestrophin-1 impairs functions of the RPE which support photoreceptor function
and will thus lead to retinal degeneration. However, the RPE function which is
influenced by bestrophin-1 is so far not identified. Previously we showed that
bestrophin-1 interacts with L-type Ca2+ channels of the CaV1.3 subtype and that
the endogenously expressed bestrophin-1 is required for intracellular Ca2+
regulation. A hallmark of Best's disease is the fast lipofuscin accumulation
occurring already at young ages. Therefore, we addressed the hypothesis that
bestrophin-1 might influence phagocytosis of photoreceptor outer segments (POS)
by the RPE. Here, siRNA knock-down of bestrophin-1 expression as well as
inhibition of L-type Ca2+ channel activity modulated the POS phagocytosis in
vitro. In vivo CaV1.3 expression appeared to be diurnal regulated with a higher
expression rate in the afternoon. Compared to wild-type littermates, Ca V 1.3 (-/
) mice showed a shift in the circadian POS phagocytosis with an increased
activity in the afternoon. Thus we suggest that mutant bestrophin-1 leads to an
impaired regulation of the POS phagocytosis by the RPE which would explain the
fast lipofuscin accumulation in Best patients.
PMID- 26427485
TI - Live-Cell Imaging of Phagosome Motility in Primary Mouse RPE Cells.
AB - The retinal pigment epithelium (RPE) is a post-mitotic epithelial monolayer
situated between the light-sensitive photoreceptors and the choriocapillaris.
Given its vital functions for healthy vision, the RPE is a primary target for
insults that result in blinding diseases, including age-related macular
degeneration (AMD). One such function is the phagocytosis and digestion of shed
photoreceptor outer segments. In the present study, we examined the process of
trafficking of outer segment disk membranes in live cultures of primary mouse
RPE, using high speed spinning disk confocal microscopy. This approach has
enabled us to track phagosomes, and determine parameters of their motility, which
are important for their efficient degradation.
PMID- 26427486
TI - RPE Cell and Sheet Properties in Normal and Diseased Eyes.
AB - Previous studies of human retinal pigment epithelium (RPE) morphology found
spatial differences in density: a high density of cells in the macula, decreasing
peripherally. Because the RPE sheet is not perfectly regular, we anticipate that
there will be differences between conditions and when and where damage is most
likely to begin. The purpose of this study is to establish relationships among
RPE morphometrics in age, cell location, and disease of normal human and AMD eyes
that highlight irregularities reflecting damage. Cadaveric eyes from 11 normal
and 3 age-related macular degeneration (AMD) human donors ranging from 29 to 82
years of age were used. Borders of RPE cells were identified with phalloidin. RPE
segmentation and analysis were conducted with CellProfiler. Exploration of
spatial point patterns was conducted using the "spatstat" package of R. In the
normal human eye, with increasing age, cell size increased, and cells lost their
regular hexagonal shape. Cell density was higher in the macula versus periphery.
AMD resulted in greater variability in size and shape of the RPE cell. Spatial
point analysis revealed an ordered distribution of cells in normal and high
spatial disorder in AMD eyes. Morphometrics of the RPE cell readily discriminate
among young vs. old and normal vs. diseased in the human eye. The normal RPE
sheet is organized in a regular array of cells, but AMD exhibited strong spatial
irregularity. These findings reflect on the robust recovery of the RPE sheet
after wounding and the circumstances under which it cannot recover.
PMID- 26427487
TI - Valproic Acid Induced Human Retinal Pigment Epithelial Cell Death as Well as its
Survival after Hydrogen Peroxide Damage is Mediated by P38 Kinase.
AB - Age-related macular degeneration (AMD) is a leading cause of legal blindness in
developed countries. Several new drugs are now available to reduce the sight
threatening complications of this disease, however, all are useful in only a
small fraction of patients and none of them prevents disease development. An
understanding of the pathogenesis of the retinal and macular degeneration is the
first step in developing preventive and fully effective treatment options for
this condition. Lifelong oxidative stress seems to be an etiologic factor. In
this study, we used cultured human retinal pigment epithelial cells to study the
mechanism of cell death and survival in cells exposed to oxidative stress. Our
studies demonstrate that valproic acid (VPA), an epigenetic factor, reduces
apoptosis in hRPE cells that were subjected to hydrogen peroxide-induced
oxidative injury by alteration in P38 kinase activity. Since VPA has been shown
to have therapeutic use in other neuronal diseases, better understanding of the
mechanism of this VPA anti-apoptotic activity may enhance its development as a
therapeutic agent.
PMID- 26427488
TI - Blockade of MerTK Activation by AMPK Inhibits RPE Cell Phagocytosis.
AB - Timely removal of shed photoreceptor outer segments by retinal pigment epithelial
cells (RPE) plays a key role in biological renewal of these highly peroxidizable
structures and in maintenance of retina health. How environmental stress cause
RPE cell dysfunction is undefined however. AMP-activated protein kinase (AMPK), a
heterotrimer of a catalytic alpha subunit and regulatory beta and gamma subunits,
maintains energy homeostasis by limiting energy utilization and/or promoting
energy production when energy supply is compromised. Intriguingly, AMPK has been
shown to be important in functions of RPE cells. In this mini-review, the role
and mechanisms of AMPK in controlling RPE cell phagocytosis are discussed.
PMID- 26427489
TI - Modulation of V-ATPase by betaA3/A1-Crystallin in Retinal Pigment Epithelial
Cells.
AB - We have previously demonstrated that betaA3/A1-crystallin, a member of the
beta/gamma-crystallin superfamily, is expressed in the astrocytes and retinal
pigment epithelial (RPE) cells of the eye. In order to understand the
physiological functions of betaA3/A1-crystallin in RPE cells, we generated
conditional knockout (cKO) mice where Cryba1, the gene encoding betaA3/A1
crystallin, is deleted specifically from the RPE using the Cre-loxP system. By
utilizing the cKO model, we have shown that this protein is required by RPE cells
for proper lysosomal degradation of photoreceptor outer segments (OS) that have
been internalized in phagosomes and also for the proper functioning of the
autophagy process. We also reported that betaA3/A1-crystallin is trafficked to
lysosomes, where it regulates endolysosomal acidification by modulating the
activity of the lysosomal V-ATPase complex. Our results show that the V-ATPase
activity in cKO RPE is significantly lower than WT RPE. Since, V-ATPase is
important for regulating lysosomal pH, we noticed that endolysosomal pH was
higher in the cKO cells compared to the WT cells. Increased lysosomal pH in cKO
RPE is also associated with reduced Cathepsin D activity. Cathepsin D is a major
lysosomal aspartic protease involved in the degradation of the OS and hence we
believe that reduced proteolytic activity contributes to impaired degradation of
OS in the cKO RPE. Reduced lysosomal activity in the cKO RPE also contributes to
the incomplete degradation of the autophagosomes. Our results also suggest that
betaA3/A1-crystallin regulates V-ATPase activity by binding to the V0 subunit of
the V-ATPase complex. Taken together, these results suggest a novel mechanism by
which betaA3/A1-crystallin regulates lysosomal function by modulating the
activity of V-ATPase.
PMID- 26427490
TI - Proteomic Profiling of Cigarette Smoke Induced Changes in Retinal Pigment
Epithelium Cells.
AB - Age-related macular degeneration (AMD) is a medical condition usually affecting
older adults and resulting in a loss of vision in the macula, the center of the
visual field. The dry form of this disease presents with atrophy of the retinal
pigment epithelium, resulting in the detachment of the retina and loss of
photoreceptors. Cigarette smoke is one main risk factor for dry AMD and increases
the risk of developing the disease by three times. In order to understand the
influence of cigarette smoke on retinal pigment epithelial cells, cultured human
ARPE-19 cells were treated with cigarette smoke extract for 24 h. Using
quantitative mass spectrometry more than 3000 proteins were identified and their
respective abundances were compared between cigarette smoke-treated and untreated
cells. Altogether 1932 proteins were quantified with at least two unique
peptides, with 686 proteins found to be significantly differentially abundant
with p > 0.05. Of these proteins the abundance of 64 proteins was at least 2-fold
down-regulated after cigarette smoke treatment while 120 proteins were 2-fold up
regulated. The analysis of associated biological processes revealed an alteration
of proteins involved in RNA processing and transport as well as extracellular
matrix remodelling in response to cigarette smoke treatment.
PMID- 26427491
TI - Reduced Metabolic Capacity in Aged Primary Retinal Pigment Epithelium (RPE) is
Correlated with Increased Susceptibility to Oxidative Stress.
AB - One of the affected tissues in age-related macular degeneration (AMD) is the
retinal pigment epithelium (RPE), a tissue that consists of terminally
differentiated cells and that accumulates damage over time. In all tissues,
mitochondria (mt), which play an essential role in both cell health (energy) and
death (initiator of apoptosis), undergo an aging process through the accumulation
of mtDNA damage, changes in mitochondrial dynamics, a reduction in biogenesis,
and mitophagy, leading to an overall reduction in mitochondrial energy production
and other non-energy-related functions. Here we have compared energy metabolism
in primary human RPE cells isolated from aborted fetus or aged donor eyes and
grown as stable monolayers. H2O2 treatment resulted in the generation of reactive
oxygen species and superoxide, an effect that was significantly augmented by age.
Mitochondrial metabolism, as analyzed by Seahorse respirometry, revealed reduced
mitochondrial oxygen consumption (ATP production) at baseline and a complete loss
of reserve capacity in aged cells. Likewise, glycolysis was blunted in aged
cells. Taken together, these studies showed that RPE cells derived from aged
donor eyes are more susceptible to oxidative stress, and exhibit a loss in
mitochondrial respiratory reserve capacity and a reduction in glycolysis. These
data suggest that while old cells may have sufficient energy at rest, they cannot
mount a stress response requiring additional ATP and reducing agents. In summary,
these data support the hypothesis that mitochondria or energy metabolism is a
valid target for therapy in AMD.
PMID- 26427492
TI - Cell phone explosion.
AB - Cell phone explosions and resultant burn injuries are rarely reported in the
scientific literature. We report a case of cell phone explosion that occurred
when a young male was listening to music while the mobile was plugged in for
charging.
PMID- 26427493
TI - Animal models of hepatotoxicity.
AB - INTRODUCTION: Liver is the largest and important organ in the body, involved in
the metabolism of food and drugs. Liver diseases are potentially life threatening
for humans. The etiology of liver disorder varied due to different reasons like
autoimmune disorder, viral infection, toxic chemical, and due to changing diet
style. Liver injury produces pathological changes like increase level of SGOT,
SGPT, TB and generation of free radical radicals. METHODS: A better understanding
of primary mechanisms is mandatory for designing of new therapeutic drugs.
Therefore, animal models are being developed to mimic human liver diseases.
Animal models are being used for several decades to study the pathogenesis of
liver disorders and related toxicities. CONCLUSION: In this review, we revealed
various animal models with their merits and demerits. Our main focus is to
explore all new and traditional animal models under broad classification like non
invasive, invasive and genetic models which directly or indirectly produce
hepatotoxicity.
PMID- 26427494
TI - Dual effects of a lectin from the green seaweed Caulerpa cupressoides var.
lycopodium on inflammatory mediators in classical models of inflammation.
AB - OBJECTIVE: Wide biotechnological investigations of only a limited number of
seaweed lectins have been performed. We previously demonstrated the anti
nociceptive and anti-inflammatory effects of a lectin isolated from the green
seaweed Caulerpa cupressoides var. lycopodium (CcL). Herein, we further studied
the mechanisms of action of CcL. METHODS: Classical acute inflammation models
induced by different flogistic agents were used to evaluate the anti-inflammatory
action of CcL. CcL was injected locally into the rat paw to verify a possible pro
inflammatory outcome. RESULTS: CcL (0.1, 1 or 10 mg/kg; i.v.) reduced the
carrageenan-induced rat paw edema and neutrophilic infiltration, which was not
altered by either mucin (inhibitor of CcL carbohydrate-binding site) or ZnPP-IX
(specific HO-1 inhibitor). Immunohistochemical analyses showed that CcL (1 mg/kg)
reduced the expression of the cytokines IL-1beta, TNF-alpha, IL-6 and COX-2. CcL
(0.1, 1 or 10 mg/kg) inhibited dextran, and CcL (1 mg/kg) inhibited histamine
induced rat paw edema. Both effects were reversed by mucin inhibition. CcL (1
mg/kg) was ineffective for the treatment of serotonin- and bradykinin-induced rat
paw edema. When injected via the i.pl. route, CcL (10 mg/kg) elicited rat paw
edema involving a wide range of mediators. CONCLUSIONS: The anti-inflammatory
action of CcL involves the inhibition of IL-1beta, TNF-alpha, IL-6 and COX-2
expression and histamine H1 receptors. When locally administered, CcL exerts pro
inflammatory actions.
PMID- 26427496
TI - WHO should commit to eradicating malaria by 2040, says Gates Foundation.
PMID- 26427495
TI - Prenatal constriction of the ductus arteriosus following maternal diclofenac
medication in the third trimester.
AB - We describe a case of a 21-year-old primigravida at 36 weeks' gestation who was
admitted to a local hospital because of abdominal pain. She was prescribed a
total of six doses of diclofenac 50 mg over 2 days. One day later, there was
difficulty registering the fetal heartbeats on cardiotocography. Ultrasound
examination revealed a fetus with ascites and pathological flow over the
tricuspid valve. The patient was referred to a tertiary centre for fetal
medicine. Fetal echocardiography revealed, in addition to ascites and tricuspid
regurgitation, a constricted ductus arteriosus, dilated right ventricle and
reduced flow in the pulmonary artery. Immediate caesarean section resulted in an
excellent neonatal outcome.
PMID- 26427497
TI - Multi-class method for biomonitoring of hair samples using gas chromatography
mass spectrometry.
AB - Currently, non-invasive biomonitoring of human exposure to organic pollutants
bases upon the analysis mainly of urine and human breast milk. While mostly
persistent organic pollutants are the center of interest, the aim of our study
was to develop a method for the determination of different chemical classes of
emerging pollutants (organophosphorus flame retardants, plastic additives such as
phthalates, bisphenol A, insecticides, antimicrobials, preservatives and musk
fragrances) in hair by gas chromatography-mass spectrometry. The preferred sample
preparation included hydrolysis of the hair with trifluoroacetic acid in methanol
followed by a liquid-liquid extraction using hexane/ethyl acetate. The validated
method is characterized by recoveries higher than 77 % for most analytes,
relative standard deviations below 16 % and limits of detection between 2 pg mg(
1) (HHCB) and 292 pg mg(-1) (propylparaben) using 50 mg of dry hair. After
respective blank corrections, bis-(2-ethylhexyl)phthalate (DEHP) and the musk
fragrance HHCB were the predominant compounds determined in all hair samples at
concentrations between 32 and 59 ng mg(-1) and 0.8-13 ng mg(-1), respectively.
The bactericide triclosan and the insect repellent N,N-diethyl-3-methylbenzamide
(DEET) were detected in selected hair samples at 2 and 0.8 ng mg(-1),
respectively.
PMID- 26427498
TI - Prediction of retention characteristics of heterocyclic compounds.
AB - The CORAL software ( http://www.insilico.eu/coral ) was used to build up
quantitative structure-property relationships (QSPRs) for the retention
characteristics of 93 derivatives of three groups of heterocyclic compounds: 2
phenyl-1,3-benzoxazoles, 4-benzylsulfanylpyridines, and benzoxazines. The QSPRs
are one-variable models based on the optimal descriptors calculated from the
molecular structure represented by simplified molecular input-line entry systems
(SMILES). Each symbol (or two undivided symbols) of SMILES is characterized by
correlation weight. The optimal descriptor is the sum of the correlation weights.
The numerical data on the correlation weights were calculated with the Monte
Carlo method by the manner which provides best correlation between endpoint and
optimal descriptor for the calibration set. The predictive ability of the model
is checked with the validation set (compounds invisible during building up of the
model). The approach has been checked with three random splits into the training,
calibration, and validation sets: all models have apparent predictive potential.
The mechanistic interpretation of the molecular features extracted from SMILES as
the promoters of increase or decrease of examined endpoints is suggested.
PMID- 26427499
TI - Separation of peptide fragments of a protein kinase C substrate fused to a beta
hairpin by capillary electrophoresis.
AB - Synthetic peptides incorporating well-folded beta-hairpin peptides possess
advantages in a variety of cell biology applications by virtue of increased
resistance to proteolytic degradation. In this study, the WKpG beta-hairpin
peptide fused to a protein kinase C (PKC) substrate was synthesized, and
capillary-electrophoretic separation conditions for this peptide and its
proteolytic fragments were developed. Fragments of WKpG-PKC were generated by
enzymatic treatment with trypsin and Pronase E to produce standards for
identification of degradation fragments in a cellular lysate. A simple buffer
system of 250 mM H3PO4, pH 1.5 enabled separation of WKpG-PKC and its fragments
by capillary electrophoresis in less than 16 min. Using a cellular lysate
produced from Ba/F3 cells, the beta-hairpin-conjugated substrate and its PKCalpha
phosphorylated product could be detected and separated from peptidase-generated
fragments produced in a cell lysate. The method has potential application for
identification and quantification of WKpG-PKC and its fragments in complex
biological systems when the peptide is used as a reporter to assay PKC activity.
PMID- 26427500
TI - Analysis of epinephrine, norepinephrine, and dopamine in urine samples of
hospital patients by micellar liquid chromatography.
AB - An analytical method based on micellar liquid chromatography was developed to
determine the concentration of three catecholamines (epinephrine, norepinephrine,
and dopamine) in urine. The detection of these compounds in urine can be useful
to diagnose several diseases, related to stress and sympathoadrenal system
dysfunction, using a non-invasive collection procedure. The sample pretreatment
was a simple dilution in a micellar solution, filtration, and direct injection,
thus avoiding time-consuming and tedious extraction steps. Therefore, there is no
need to use an internal standard. The three catecholamines were eluted using a
C18 column and a mobile phase of 0.055 M sodium dodecyl sulfate-1.5% methanol
buffered at pH 3.8 running at 1.5 mL/min under isocratic mode in less than 25
min. The detection was performed by amperometry applying a constant potential of
+0.5 V. The procedure was validated following the guidelines of the European
Medicines Agency in terms of the following: calibration range (0.09-5 MUg/mL),
linearity (r(2) > 0.9995), limit of detection (0.02 MUg/mL), within- and between
run accuracy (-6.5 to +8.4%) and precision (<10.2%), dilution integrity, matrix
effect, robustness (<8.4), and stability. The obtained values were below those
required by the guide. The method was rapid, easy-to-handle, eco-friendly, and
safe and provides reliable quantitative data, and is thus useful for routine
analysis. The procedure was applied to the analysis of epinephrine,
norepinephrine, and dopamine in urine samples from patients of a local hospital.
PMID- 26427501
TI - New ex-ovo colorectal-cancer models from different SdFFF-sorted tumor-initiating
cells.
AB - Despite effective treatments, relapse of colorectal cancer (CRC) is frequent, in
part caused by the existence of tumor-initiating cells (TICs). Different subtypes
of TICs, quiescent and activated, coexist in tumors, defining the tumor
aggressiveness and therapeutic response. These subtypes have been sorted by
hyperlayer sedimentation field-flow fractionation (SdFFF) from WiDr and HCT116
cell lines. On the basis of a new strategy, including TIC SdFFF sorting, 3D
Matrigel amplification, and grafting of corresponding TIC colonies on the chick
chorioallantoic membrane (CAM), specific tumor matrices could be obtained. If
tumors had similar architectural structure with vascularization by the host
system, they had different proliferative indices in agreement with their initial
quiescent or activated state. Protein analysis also revealed that tumors obtained
from a population enriched for "activated" TICs lost "stemness" properties and
became invasive. In contrast, tumors obtained from a population enriched for
"quiescent" TICs kept their stemness properties and seemed to be less
proliferative and invasive. Then, it was possible to produce different kinds of
tumor which could be used as selective supports to study carcinogenesis and
therapy sensitivity.
PMID- 26427502
TI - Development of a MAb-based immunoassay for the simultaneous determination of O,O
diethyl and O,O-dimethyl organophosphorus pesticides in vegetable and fruit
samples pretreated with QuEChERS.
AB - To develop a broad-specificity immunoassay for organophosphorus pesticides (OPs),
a broad-specificity monoclonal antibody (MAb) for OPs against a generic hapten,
O,O-diethyl O-(3-carboxyphenyl) phosphorothioate with the carboxy group in the
meta position of the benzene ring, was produced. Eight haptens were prepared and
covalently attached to ovalbumin (OVA) for use as coating antigens, and the
optimum coating antigen was selected. Then, a sensitive and broadly class
selective competitive indirect enzyme-linked immunosorbent assay (ciELISA) based
on the MAb and the optimum coating antigen (hapten H-OVA, possessing an O,O
dimethyl generic structure and linked through a linear spacer arm) was developed
and optimized. The MAb developed in this study showed quite different cross
reactivity and selectivity compared to previously produced anti-OPs broad
specificity MAbs. Specifically, the MAb showed high and uniform sensitivity to
seven O,O-diethyl OPs and six O,O-dimethyl OPs. With the optimum ciELISA, the
IC50 values of the 13 OPs were determined as 23.1~151.2 ng mL(-1). The average
IC50 and coefficient of variation (CV) for the IC50 values of the 13 OPs were
74.6 ng mL(-1) and 33.9%, respectively. For the recovery study, a QuEChERS
approach based on dispersive solid-phase extraction (d-SPE) was implemented to
decrease the matrix effects of vegetable and fruit samples. The recoveries of six
representative OPs from the spiked samples ranged from 89.4 to 135.5%; the CV
ranged from 3.5 to 15.7%. The ciELISA was also applied to real samples, followed
by confirmation with gas chromatography-tandem mass spectrometry (GC-MS/MS)
analysis. The results demonstrated that the ciELISA is suitable for monitoring OP
contamination in vegetable and fruit samples.
PMID- 26427503
TI - Novel imidazolium-embedded N,N-dimethylaminopropyl-functionalized silica-based
stationary phase for hydrophilic interaction/reversed-phase mixed-mode
chromatography.
AB - A novel imidazolium-embedded N,N-dimethylaminopropyl-functionalized silica-based
stationary phase (Sil-ImCl) was prepared and further used for hydrophilic
interaction/reversed-phase mixed-mode chromatography. The Sil-ImCl stationary
phase was respectively characterized by Fourier transform infrared spectrometry,
thermogravimetric analysis, and element analysis. A variety of hydrophilic or
hydrophobic compounds were used to evaluate the retention mechanisms of the
developed stationary phase, and the effects of buffer salt concentration and pH
of mobile phase on the retention of these compounds were also investigated. The
developed stationary phase was successfully applied for separation of nucleosides
and nucleic acid bases, water-soluble vitamins, phenols, and positional isomers.
Moreover, simultaneous separation of polar and nonpolar compounds was also
achieved with high resolution, outperforming the commercially available C8 column
and amino column. Furthermore, the Sil-ImCl stationary phase has been
successfully applied for separation of secondary metabolites of Hansfordia
sinuosae. All these results demonstrate that the Sil-ImCl stationary phase might
be promising for separation of complex polar and nonpolar compounds with high
efficiency, especially in biological industry.
PMID- 26427504
TI - Immobilizing affinity proteins to nitrocellulose: a toolbox for paper-based assay
developers.
AB - To enable enhanced paper-based diagnostics with improved detection capabilities,
new methods are needed to immobilize affinity reagents to porous substrates,
especially for capture molecules other than IgG. To this end, we have developed
and characterized three novel methods for immobilizing protein-based affinity
reagents to nitrocellulose membranes. We have demonstrated these methods using
recombinant affinity proteins for the influenza surface protein hemagglutinin,
leveraging the customizability of these recombinant "flu binders" for the design
of features for immobilization. The three approaches shown are: (1) covalent
attachment of thiolated affinity protein to an epoxide-functionalized
nitrocellulose membrane, (2) attachment of biotinylated affinity protein through
a nitrocellulose-binding streptavidin anchor protein, and (3) fusion of affinity
protein to a novel nitrocellulose-binding anchor protein for direct coupling and
immobilization. We also characterized the use of direct adsorption for the flu
binders, as a point of comparison and motivation for these novel methods.
Finally, we demonstrated that these novel methods can provide improved
performance to an influenza hemagglutinin assay, compared to a traditional
antibody-based capture system. Taken together, this work advances the toolkit
available for the development of next-generation paper-based diagnostics.
PMID- 26427505
TI - A selective biomarker for confirming nitrofurazone residues in crab and shrimp
using ultra-performance liquid chromatography-tandem mass spectrometry.
AB - Reliably detecting nitrofurazone (NFZ) residues in farmed crab and shrimp was
previously hindered by lack of appropriately specific analytical methodology.
Parent NFZ rapidly breaks down in meat, and the commonly used side-chain
metabolite, semicarbazide (SEM), is non-specific as it occurs naturally in
crustacean shell often leading to 'false positive' detections in meat. Using 5
nitro-2-furaldehyde (NF) as marker metabolite, following pre-column
derivatization with 2,4-dinitrophenylhydrazine (DNPH), ultra-performance liquid
chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis in negative
electrospray ionization mode enabled confirmation of NFZ residues in deliberately
treated whole crab, crab meat and shrimp meat, with a limit of detection (LOD)
and limit of quantification (LOQ) below 1 ng g(-1). Meanwhile, the derivatives of
DNPH-NF were synthesized for the first time, purified by preparative liquid
chromatography and structure characterized with nuclear magnetic resonance
spectroscopy ((1)H-NMR). The purity of derivative was checked by ultra
performance liquid chromatography-tunable ultraviolet (UPLC-TUV), and the
contents were beyond 99.9%. For comparison purposes, crustacean samples were
analysed using both NF and SEM marker metabolites. NFZ treatment was revealed by
both NF and SEM marker metabolites, but untreated crab also showed measurable
levels of SEM which could potentially be misinterpreted as evidence of illegal
NFZ use.
PMID- 26427506
TI - Stable isotope tracing: a powerful tool for selenium speciation and metabolic
studies in non-hyperaccumulator plants (ryegrass Lolium perenne L.).
AB - Selenium is both essential and toxic for mammals; the range between the two roles
is narrow and not only dose-dependent but also related to the chemical species
present in foodstuff. Unraveling the metabolism of Se in plants as a function of
Se source may thus lead to ways to increase efficiency of fertilization
procedures in selenium deficient regions. In this study, stable-isotope tracing
was applied for the first time in plants to simultaneously monitor the bio
incorporation of two inorganic Se species commonly used as foodstuff enrichment
sources. Occurrence and speciation of Se coming from different Se sources were
investigated in root and leaf extracts of ryegrass (Lolium perenne L.), which had
been co-exposed to two labeled Se species ((77)SeIV and (82)SeVI). Although the
plant absorbed similar amounts of Se when supplied in the form of selenite or
selenate, the results evidenced marked differences in speciation and tissues
allocation. Selenite was converted into organic forms incorporated mostly into
high molecular weight compounds with limited translocation to leaves, whereas
selenate was highly mobile being little assimilated into organic forms. Double
spike isotopic tracer methodology makes it possible to compare the metabolism of
two species-specific Se sources simultaneously in a single experiment and to
analyze Se behavior in not-hyperaccumulator plants, the ICP-MS sensitivity being
improved by the use of enriched isotopes.
PMID- 26427507
TI - Analysis of gamma-hydroxy butyrate by combining capillary electrophoresis
indirect detection and wall dynamic coating: application to dried matrices.
AB - gamma-Hydroxybutyric acid (GHB) is a powerful central nervous system depressant,
currently used in medicine for the treatment of narcolepsy and alcohol
dependence. In recent years, it has gained popularity among illegal club drugs,
mainly because of its euphoric effects as well as doping agent and date rape
drug. The purpose of the present work was the development of a rapid analytical
method for the analysis of GHB in innovative biological matrices, namely dried
blood spots (DBSs) and dried urine spots (DUSs). The analytical method is based
on capillary zone electrophoresis with indirect UV absorption detection at 210 nm
and capillary wall dynamic coating. The background electrolyte is composed of a
phosphate buffer containing nicotinic acid (probe for detection) and
cetyltrimethylammonium bromide (CTAB, reversal of electroosmosis in wall dynamic
coating). The influence of probe and CTAB concentration, together with buffer pH,
on migration time and signal response was investigated. Under the optimized
conditions, analytical linearity and precision were satisfactory; absolute
recovery values were also high (>90 %); the use of dried matrices (DBSs and DUSs)
was advantageous as an alternative matrix to classical ones. No interferences
were found either from the most common exogenous or from endogenous compounds.
This analytical approach can offer a rapid, precise and accurate method for GHB
determination in innovative biological samples, which could be important for
screening purposes in clinical and forensic toxicology. Graphical Abstract CE
method, by combined indirect UV detection and dynamic coating, for GHB
determination in DBSs and DUSs.
PMID- 26427509
TI - Commentary on: isolation and differentiation potential of human mesenchymal stem
cells from adipose tissue harvested by water jet-assisted liposuction.
PMID- 26427508
TI - Serum urate gene associations with incident gout, measured in the Framingham
Heart Study, are modified by renal disease and not by body mass index.
AB - We hypothesized that serum urate-associated SNPs, individually or collectively,
interact with BMI and renal disease to contribute to risk of incident gout. We
measured the incidence of gout and associated comorbidities using the original
and offspring cohorts of the Framingham Heart Study. We used direct and imputed
genotypes for eight validated serum urate loci. We fit binomial regression models
of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and
all main and interaction effects of the eight serum urate SNPs with BMI and renal
disease. Models were also fit with a genetic risk score for serum urate levels
which corresponds to the sum of risk alleles at the eight SNPs. Model covariates,
age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E
11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936
(P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident
gout. No BMI by SNP or BMI by serum urate genetic risk score interactions were
statistically significant, but renal disease by rs1106766 was statistically
significant (P = 6.12E-03). We demonstrated that minor alleles of rs1106766
(intergenic, INHBC) were negatively associated with the risk of incident gout in
subjects without renal disease, but not for individuals with renal disease. These
analyses demonstrate that a significant component of the risk of gout may involve
complex interplay between genes and environment.
PMID- 26427510
TI - The National Mental Health Commission Report: Evidence based or ideologically
driven?
PMID- 26427511
TI - A record linkage study of antidepressant medication use and weight change in
Australian adults.
AB - OBJECTIVE: Antidepressant use is widespread. While weight gain is a commonly
reported side-effect of antidepressant use and has the potential to affect
population health, there is little large-scale population-based evidence on the
issue, particularly for long-term use (?12 months). The aim of this study is to
investigate the association between antidepressant use and weight change,
including whether this relationship varies according to antidepressant class,
recency of use, duration of use and dose. METHODS: Annual percentage weight
change was calculated from self-reported weight at two time-points from 20,751
participants aged ?45 years from the 45 and Up Study - a population-based cohort
study from New South Wales, Australia. Antidepressant use, ascertained from
linked pharmaceutical data, from 19 months before baseline until end of follow-up
(mean = 3.3 years of follow-up), was categorised as current, past-only, non
persistent or non-use. The association between antidepressant use and weight
change was modelled using linear and multinomial logistic regressions and
according to antidepressant class, recency, duration and dose. RESULTS:
Antidepressants were dispensed to 23% of participants (n = 4748) during the study
period. Current antidepressant users were significantly more likely to gain >3%
of their body weight annually than non-users (adjusted relative risk ratio =
1.19; 95% confidence interval: [1.03, 1.38]); the risk increased with increasing
dose among current users (p[trend] = 0.003). Risk of weight gain did not vary
significantly according to antidepressant class, recency or duration of use;
however, statistical power was limited. No significant associations were found
between antidepressant use and weight loss. CONCLUSION: Current antidepressant
use was associated with modest but statistically significant annual gains in
weight, with similar effects observed across the different classes of
antidepressants used.
PMID- 26427512
TI - Degradation of miR-21 induces apoptosis and inhibits cell proliferation in human
hepatocellular carcinoma.
AB - MicroRNAs (miRNAs) are small non-coding RNAs, 18-25 nucleotides long and have an
important role in post-transcriptional regulation of gene. Several aspects of
cellular activities such as cell growth, proliferation and differentiation are
regulated by miRNAs. In many cancers and malignancies, up- or downregulation of
different miRNAs has been reported. In human hepatocellular carcinoma (HCC),
upregulation of miR-21 has been reported in human in vitro studies. Here, we made
an assessment of the effect of miR-21 degradation on viability and apoptosis of
HCC cell line (HepG2) using locked nucleic acid (LNA). At different time points
(24, 48, 72 h) after LNA-anti-miR-21 transfection, 3-[4,5-dimethylthiazol-2-yl]
2, 5-diphenyl tetrazolium bromide assay and Annexin/propidium iodide staining
were performed. The results show that miR-21 degradation can decrease the
viability of cells, mainly by induction of apoptosis and necrosis. These findings
suggest that degradation of miR-21 could be used as a novel approach in treatment
of HCC.
PMID- 26427513
TI - Integrated analysis of gene expression and genomic aberration data in
osteosarcoma (OS).
AB - Cytogenetic analyses have revealed that complex karyotypes with numerous and
highly variable genomic aberrations including single-nucleotide polymorphisms
(SNPs) and copy number variants (CNVs), are observed in most of the conventional
osteosarcomas (OSs). Several genome-wide studies have reported that the
dysregulated expression of many genes is correlated with genomic aberrations in
OS. We first compared OS gene expression in Gene Expression Omnibus (GEO) data
sets and genomic aberrations in International Cancer Genome Consortium (ICGC)
database to identify differentially expressed genes (DEGs) associated with SNPs
or CNVs in OS. Then the function annotation of SNP- or CNV-associated DEGs was
performed in terms of gene ontology analysis, pathway analysis and protein
protein interactions (PPIs). Finally, the expression of genes correlated with
both SNPs and CNVs were confirmed by quantitative reverse-transcription PCR.
Eight publicly available GEO data sets were obtained, and a set of 979 DEGs were
identified (472 upregulated and 507 downregulated DEGs). Moreover, we obtained
1039 SNPs mapped in 938 genes, and 583 CNV sites mapped in 2915 genes. Comparing
genomic aberrations and DGEs, we found 41 SNP-associated DEGs and 124 CNV
associated DEGs, in which 7 DGEs were associated with both SNPs and CNVs,
including WWP1, EXT1, LDHB, C8orf59, PLEKHA5, CCT3 and VWF. The result of
function annotation showed that ossification, bone development and skeletal
system development were the significantly enriched terms of biological processes
for DEGs. PPI network analysis showed that CCT3, COPS3 and WWP1 were the
significant hub proteins. We conclude that these genes, including CCT3, COPS3 and
WWP1 are candidate driver genes of importance in OS tumorigenesis.
PMID- 26427515
TI - The professionalization and training of psychologists: The place of clinical
wisdom.
AB - OBJECTIVE: The current study examines how clinical wisdom develops and how it
both is and can be influenced by professional training processes. In this way,
the project is studying the intersection of developmental and systemic processes
related to clinical wisdom. METHOD: Researchers analyzed the interviews of
psychologists practicing in the USA and Canada who were nominated for their
clinical wisdom by their peers. These interviews explored how graduate training
and professionalization were thought to influence the development of clinical
wisdom and were subjected to an adapted grounded theory analysis. RESULTS: The
findings described both professional and personal disincentives toward developing
wisdom, including the dangers of isolation. Therapists reported concerns about
educational systems that rewarded quick answers instead of thoughtful questioning
in processes of admittance, training, and accreditation. Findings emphasized the
importance of teaching multiple psychotherapy orientations, critical self- and
professional-reflection skills, and openly supporting graduate students'
curiosities and continued professional engagement. CONCLUSIONS: Recommended
principles for training are put forward for the development and evaluation of
psychotherapy training programs that aim to foster clinical wisdom. These
principles complement training models focused upon clinical competence by helping
trainees to develop a foundation for clinical wisdom.
PMID- 26427514
TI - Down-regulation of IKKbeta expression in glioma-infiltrating
microglia/macrophages is associated with defective inflammatory/immune gene
responses in glioblastoma.
AB - Glioblastoma (GBM) is an aggressive malignancy associated with profound host
immunosuppression. Microglia and macrophages infiltrating GBM acquire the pro
tumorigenic, M2 phenotype and support tumor invasion, proliferation, survival,
angiogenesis and block immune responses both locally and systematically.
Mechanisms responsible for immunological deficits in GBM patients are poorly
understood. We analyzed immune/inflammatory gene expression in five datasets of
low and high grade gliomas, and performed Gene Ontology and signaling pathway
analyses to identify defective transcriptional responses. The expression of many
immune/inflammatory response and TLR signaling pathway genes was reduced in high
grade gliomas compared to low grade gliomas. In particular, we found the reduced
expression of the IKBKB, a gene coding for IKKbeta, which phosphorylates IkappaB
proteins and represents a convergence point for most signal transduction pathways
leading to NFkappaB activation. The reduced IKBKB expression and IKKbeta levels
in GBM tissues were demonstrated by qPCR, Western blotting and
immunohistochemistry. The IKKbeta expression was down-regulated in
microglia/macrophages infiltrating glioblastoma. NFkappaB activation, prominent
in microglia/macrophages infiltrating low grade gliomas, was reduced in
microglia/macrophages in glioblastoma tissues. Down-regulation of IKBKB
expression and NFkappaB signaling in microglia/macrophages infiltrating
glioblastoma correlates with defective expression of immune/inflammatory genes
and M2 polarization that may result in the global impairment of anti-tumor immune
responses in glioblastoma.
PMID- 26427517
TI - Quote ... unquote.
PMID- 26427516
TI - Intuition in medical practice: A reflection on Donald Schon's reflective
practitioner.
AB - In a recent commentary, Dr. Abhishek Biswas asks the question whether physicians
should rely on their "gut feeling" when making clinical decisions. Biswas
describes a situation where his intuition resulted in an immediate course of
action that prompted urgent medical attention for a patient who had "routine"
pain. Inspired by the author's account, I would like to further Biswas'
discussion and examine its importance using the educational theories of Donald
Schon and his concept of the reflective practitioner. Schon argues that technical
knowledge alone is not sufficient to solve the complex problems that
professionals face on a daily basis and intuition, developed through a reflective
practice, is crucial for any professional's practice, especially in a time of
greater uncertainty in the workplace.
PMID- 26427518
TI - A critical appraisal of the selegiline transdermal system for major depressive
disorder.
AB - The selegiline transdermal system (STS) is the first antidepressant transdermal
medication approved by the US FDA for the treatment of major depressive disorder.
Its unique antidepressant delivery system allows for steady release of selegiline
over 24 h with minimal fluctuation in drug serum levels. It is able to deliver
high enough central nervous system concentrations required for an antidepressant
effect without substantially inhibiting Monoamine oxidase-A in the
gastrointestinal and hepatic system, thereby reducing the risk of tyramine
hypertensive crises especially at the lowest doses. Patient adherence
theoretically could be improved due to ease of use and once-daily dosing when
compared to oral counterparts' need for multiple daily doses. Clinical trials
have established that doses between 6 and 12 mg over 24 h have been effective for
major depressive disorder and tolerated among patients. Episodes of hypertensive
crisis with STS have been minimally reported thus far. Overall, STS appears to be
an effective agent for major depressive disorder when held to regulatory
standards and post marketing analyses. This paper reviews the pharmacologic
characteristics of STS and results of studies investigating its clinical efficacy
and safety.
PMID- 26427519
TI - Controlled-release dinoprostone insert versus Foley catheter for labor induction:
a meta-analysis.
AB - OBJECTIVE: To compare the effectiveness and safety of controlled-release
dinoprostone insert with Foley catheter balloon for cervical ripening and labor
induction. METHODS: PubMed, Cochrane Central Register of Controlled Trials, Web
of Science, and China Knowledge Resource Integrated Database were searched. Only
randomized controlled trials comparing controlled-release dinoprostone insert
with Foley catheter balloon were included. Risk ratio (RR) or mean difference
(MD) with 95% confidence interval (CI) was calculated. RESULTS: Six studies were
included with 731 women received dinoprostone insert and 722 Foley catheter. Time
from induction to delivery was significantly shortened in dinoprostone insert
group compared to Foley catheter group (MD 5.73 h, 95% CI 1.26-10.20). There were
no significant differences in vaginal delivery within 24 h (RR 0.75, 95% CI 0.43
1.30) or cesarean section (RR 0.94, 95% CI 0.80-1.12) between two ripening
methods. Dinoprostone insert was related with increased rate of excessive uterine
contraction (RR 0.07, 95% CI 0.03-0.19), but less oxytocin use (RR 1.86, 95% CI
1.25-2.77) when compared with Foley catheter. CONCLUSIONS: Induction of labor
with controlled-release dinoprostone insert seems to be more effective than Foley
catheter. However, the former method causes excessive uterine contraction more
frequently.
PMID- 26427520
TI - Nitrogen-Doped Graphene Quantum Dots as a New Catalyst Accelerating the
Coordination Reaction between Cadmium(II) and 5,10,15,20-Tetrakis(1-methyl-4
pyridinio)porphyrin for Cadmium(II) Sensing.
AB - Small molecules or metal ions can be employed as catalysts to accelerate
metalloporphyrin formation. Herein, we for the first time report the coordination
reaction between cadmium(II) and 5,10,15,20-tetrakis(1-methyl-4
pyridinio)porphyrin can be accelerated by nitrogen-doped graphene quantum dots
(NGQDs). This catalytic reaction results in the change of the absorption of
porphyrins and the fluorescence of NGQDs as a result of the inner filter effect
(IFE) of the porphyrins on the assembled NGQDs. Both signals can be used for
rapid and sensitive determination of metal ions. The present work promises a
novel strategy for constructing sensors for metal ions.
PMID- 26427521
TI - Kaurane diterpenes as mitochondrial alterations preventive agents under
experimental oxidative stress conditions.
AB - CONTEXT: Foliol, linearol, and sidol are the most common diterpenes found in
Sideritis L. spp. (Lamiaceae) with a wide range of demonstrated properties
including anti-inflammatory, antioxidant, and anti-apoptotic effects. OBJECTIVE:
For the first time, the present work was studied for the potential protective
role of these kaurane-type diterpenes on mitochondrial oxidative stress induced
by H2O2 in the human astrocytoma U373-MG cell line and in the rat adrenal
pheochromocytoma PC12 cell line. MATERIALS AND METHODS: Mitochondrial protection
was assayed at 5 and 10 uM concentrations for 24 h (for kaurane diterpenes) and
H2O2 as oxidative stress inducer (0.1 mM for PC12 cells and 1 mM for U373-MG, for
30 min). ATP concentration was determined by high-performance liquid
chromatography (HPLC), and changes in mitochondrial membrane potential, caspase-3
activity as well as in cytosolic and mitochondrial calcium levels were assessed
by fluorometric techniques, by using specific fluorescent probes. RESULTS:
Pretreatments for 24 h with linearol and sidol, prior to H2O2 exposure, acted as
mitochondrial alterations preventive agents by increasing membrane potential
(over 40-60% in PC12 cells and over 10-20% in U373-MG), restoring both cytosolic
and mitochondrial calcium homeostasis (linearol at 10 uM caused a 3.5-fold
decrease in cytosolic calcium concentration in PC12 cells), decreasing caspase-3
activity (over 1.25-1.5-fold for linearol and sidol) and avoiding ATP depletion
(linearol increased over 20% ATP level in both cell types). CONCLUSION: Our
results suggest that linearol and sidol could provide protective activity by
targeting mitochondria in response to the deleterious changes induced by H2O2.
PMID- 26427522
TI - Pharmacogenomics in the treatment of lung cancer: an update.
AB - Significant advances have been made in the analysis of the human genome in the
first decades of the 21st century and understanding of tumor biology has matured
greatly. The identification of tumor-associated mutations and the pathways
involved has led to the development of targeted anticancer therapies. However,
the challenge now in using chemotherapy to treat nonsmall-cell lung cancer is to
identify more molecular markers predictive of drug sensitivity and determine the
optimal drug sequences in order to tailor treatment to each patient. This
approach could permit selection of patients who could benefit most from a
specific type of chemotherapy by matching their tumor and individual genetic
profile. Nevertheless, this potential has been limited so far by reliance on the
single biomarker approach, though this is now on the way to being overcome
through whole genome studies.
PMID- 26427523
TI - Transferring research from researchers to knowledge users: the importance of
relationships and getting them right.
PMID- 26427524
TI - The challenge of creating a 'Welsh NHS'.
AB - Health policy in the UK has been greatly affected by devolution, with growing
divergence in policy and practice across the four UK countries. Since 1999, Wales
has created distinctive policies and structures and made some progress in
improving health and services, despite obstacles. These include financial and
demographic challenges faced elsewhere and others rooted in local attitudes and
expectations and in the nature of the Welsh constitutional settlement.
PMID- 26427525
TI - An innovative strategy to increase a professional workforce: the fast track
initiative for health visitors in England.
AB - OBJECTIVES: Fast tracking is one strategy that organizations use to ameliorate
workforce shortfalls by attracting new recruits, and accelerating their skills
development and experience. In response to the Government's target of rapidly
expanding the number of health visitors in England's National Health Service, the
fast track initiative was launched to recruit newly qualified (fast track) as
well as experienced (standard entry) nurses and midwives onto health visiting
programmes. This paper evaluates the fast track initiative, from the perspective
of fast track and standard entry students, practice teachers and health visitor
managers. METHODS: A mixed methods design was used comprising a questionnaire
survey (n = 71 students), semi-structured interviews (n = 37 students), telephone
interviews (n = 13 managers) and six focus groups (n = 24 practice teachers).
Data were collected between April 2012 and July 2013. Descriptive statistics, t
tests and the Pearson Chi-square test were used to analyse the quantitative data.
The qualitative data were analysed thematically. RESULTS: Motivations for health
visiting as a career choice were similar for fast track and standard entry
students, with career progression and interest in health promotion being key
motivators. There was consensus that personal qualities and characteristics were
more important than experience or qualifications. However, fast track students
were significantly less confident about their public health competencies in
leadership and management (p < 0.05) and communication (p < 0.02). Practice
teachers and managers also reported that fast track students required more
intensive supervision particularly at the beginning of the programme. Programme
completion including pass rates and academic achievement showed no significant
difference by route of entry (p > 0.5). CONCLUSION: Fast tracking offers a useful
recruitment strategy in order to expand the health visitor workforce, but
longitudinal research is needed to confirm benefits such as retention and career
trajectories.
PMID- 26427526
TI - A cigar by any other name would taste as sweet.
PMID- 26427527
TI - Economic burden from smoking-related diseases in Thailand.
AB - OBJECTIVE: To assess economic burden attributable to smoking in Thailand in 2009.
METHODS: A prevalence-based, disease-specific cost of illness approach was used
to estimate the direct medical costs, indirect medical costs, productivity loss
due to premature deaths and absenteeism caused by smoking-related diseases.
Direct healthcare costs were obtained from the inpatient and outpatient charge
database at the National Health Security Office and the Central Office for
Healthcare Information. Indirect healthcare costs were obtained from the Health
and Welfare Survey. The household Socioeconomic Survey provided data on income of
the population. Costs were estimated for 7 disease groups, namely, lung cancer,
chronic obstructive pulmonary disease (COPD), cardiovascular disease (CVD), upper
aerodigestive tract cancer, other cancer, other respiratory diseases and other
medical conditions. Smoking Attributable Fractions were derived from the 2009
Thai Burden of Disease study. RESULTS: Total economic burden of smoking amounted
to 74.88 billion Thai Baht (THB) (95% CI 74.59 to 75.18) (US$2.18, 95% CI US$2.17
to US$2.19 billion). Of this, most of the burden resulted from productivity loss
62.24 billion THB (95% CI 62.05 to 62.44) (US$1.81, 95% CI US$1.81 to US$1.82
billion). Total medical cost was 12.64 billion THB (12.44 to 12.85) (US$0.37, 95%
CI US$0.36 to US$0.37 billion). Excluding other medical conditions, the direct
healthcare costs were highest for CVD, followed by COPD and other respiratory
diseases, respectively. All together, the total cost of smoking accounted for
0.78% (95% CI 0.78% to 0.79%) of the national gross domestic product and about
18.19% (95% CI 18.12% to 18.27%) of total health expenditure. CONCLUSIONS: The
total economic loss from smoking-related diseases highlights the significant loss
to the society, health sector and the country's economy. Such information is
crucial for informing national public health policy, particularly when a conflict
arises between the economy and health.
PMID- 26427528
TI - Assessing tobacco marketing receptivity among youth: integrating point of sale
marketing, cigarette package branding and branded merchandise.
AB - BACKGROUND: As countries prohibit tobacco marketing through traditional channels,
marketing at point of sale (PoS) and through tobacco packaging is increasingly
important for promoting tobacco consumption. OBJECTIVES: Assess the validity of a
novel marketing receptivity index that considers frequency of PoS exposures,
tobacco brand recall and ownership of branded merchandise. METHODS: Data come
from a cross-sectional survey of 3172 secondary school students in Argentina.
Questions assessed frequency of going to stores where tobacco is often sold; cued
recall of brand names for 3 cigarette packages with brand name removed and
ownership of branded merchandise. A four-level marketing receptivity index was
derived: low PoS exposure only; high PoS exposure or recall of 1 brand; recall of
2 or more brands; and ownership of branded merchandise. Indicators of marketing
receptivity and smoking involvement were regressed on the index, including in
adjusted models that controlled for sociodemographics, social influences and
sensation seeking. FINDINGS: Among never-smokers, the index had independent
positive associations with smoking susceptibility (ie, adjusted OR (AOR)2v1=1.66;
AOR3v1=1.64; AOR4v1=2.95), willingness to try a specific brand (ie, AOR2v1=1.45;
AOR3v1=2.38; AOR4v1=2.20) and positive smoking expectancies (ie, Badj 2v1=0.09;
Badj 3v1=0.18; Badj 4v1=0.34). A more marked dose-response independent
association was found with current smoking behaviour (ie, AOR2v1=2.47;
AOR3v1=3.16; AOR4v1=3.62). CONCLUSIONS: The marketing receptivity index was
associated with important variation in smoking-related perceptions, intentions
and behaviour among Argentine adolescents. Future research should determine the
predictive validity and generalisability of this measure to other contexts,
including the explanatory power gained by integrating cigarette package brand
recognition tasks.
PMID- 26427529
TI - Histone deacetylase inhibition reduces hypothyroidism-induced neurodevelopmental
defects in rats.
AB - Thyroid hormone (TH) through its receptor (TRalpha/beta) influences spatio
temporal regulation of its target gene repertoire during brain development.
Though hypothyroidism in WT rodent models of perinatal hypothyroidism severely
impairs neurodevelopment, its effect on TRalpha/beta knockout mice is less
severe. An explanation to this paradox is attributed to a possible repressive
action of unliganded TRs during development. Since unliganded TRs suppress gene
expression through the recruitment of histone deacetylase (HDACs) via co
repressor complexes, we tested whether pharmacological inhibition of HDACs may
prevent the effects of hypothyroidism on brain development. Using valproate, an
HDAC inhibitor, we show that HDAC inhibition significantly blocks the deleterious
effects of hypothyroidism on rat cerebellum, evident by recovery of TH target
genes like Bdnf, Pcp2 and Mbp as well as improved dendritic structure of
cerebellar Purkinje neurons. Together with this, HDAC inhibition also rescues
hypothyroidism-induced motor and cognitive defects. This study therefore provides
an insight into the role of HDACs in TH insufficiency during neurodevelopment and
their inhibition as a possible therapeutics for treatment.
PMID- 26427530
TI - What Influences Patient-Therapist Interactions in Musculoskeletal Physical
Therapy? Qualitative Systematic Review and Meta-Synthesis.
AB - BACKGROUND: Musculoskeletal physical therapy involves both specific and
nonspecific effects. Nonspecific variables associated with the patient,
therapist, and setting may influence clinical outcomes. Recent quantitative
research has shown that nonspecific factors, including patient-therapist
interactions, can influence treatment outcomes. It remains unclear, however, what
factors influence patient-therapist interaction. PURPOSE: This qualitative
systematic review and meta-synthesis investigated patients' and physical
therapists' perceptions of factors that influence patient-therapist interactions.
DATA SOURCES: Eleven databases were searched independently. STUDY SELECTION:
Qualitative studies examining physical therapists' and patients' perceptions of
factors that influence patient-therapist interactions in musculoskeletal settings
were included. DATA EXTRACTION: Two reviewers independently selected articles,
assessed methodological quality using the Critical Appraisal Skills Programme
(CASP), and performed the 3 stages of analysis: extraction of findings, grouping
of findings (codes), and abstraction of findings. DATA SYNTHESIS: Thirteen
studies were included. Four themes were perceived to influence patient-therapist
interactions: (1) physical therapist interpersonal and communication skills (ie,
presence of skills such as listening, encouragement, confidence, being empathetic
and friendly, and nonverbal communication), (2) physical therapist practical
skills (ie, physical therapist expertise and level of training, although the
ability to provide good education was considered as important only by patients),
(3) individualized patient-centered care (ie, individualizing the treatment to
the patient and taking patient's opinions into account), and (4) organizational
and environmental factors (ie, time and flexibility with care and appointments).
LIMITATIONS: Only studies published in English were included. CONCLUSIONS: A mix
of interpersonal, clinical, and organizational factors are perceived to influence
patient-therapist interactions, although research is needed to identify which of
these factors actually influence patient-therapist interactions. Physical
therapists' awareness of these factors could enhance patient interactions and
treatment outcomes. Mechanisms to best enhance these factors in clinical practice
warrant further study.
PMID- 26427531
TI - Root resorption of self-ligating and conventional preadjusted brackets in severe
anterior crowding Class I patients: a longitudinal retrospective study.
AB - BACKGROUND: To test the null hypothesis that there is no difference in the apical
root resorption seen after orthodontic treatment with the conventional brackets
and the self-ligating brackets. METHODS: Pre-treatment and post-treatment
periapical radio-graphs of 70 patients, (35 treated with the Damon3 0.022"
bracket and 35 with the 0.022" 3 M bracket) were studied. The long cone
paralleling technique was used for all the radio-graphs. Any image distortion
between the pre-treatment and post-treatment radio-graph was calculated and
compensated for by using the crown length measurements, on the assumption that
the crown length remains unaltered during the treatment period. Quantitative
measurements of crown and root lengths for the maxillary and the mandibular
central and lateral incisors were compared. Means and standard deviations for the
percentage root resorption per tooth group were calculated. A paired t-test and
non paired t-test analysis was performed to determine whether there was an
appliance, treatment time, or initial age effect on the amount of root resorption
seen after treatment. RESULT: No statistically significant difference in root
resorption between the two appliance systems was found. The patient's degree of
root resorption were graded as grade 1 and grade 2 in the self-ligating group
which is more than the conventional group. CONCLUSIONS: There was no significant
difference in root resorption between self-ligating brackets and conventional
brackets in severe crowding incisors subjects.
PMID- 26427532
TI - Women's satisfaction with childbirth care in Felege Hiwot Referral Hospital,
Bahir Dar city, Northwest Ethiopia, 2014: cross sectional study.
AB - BACKGROUND: Globally, each year more than half million women die from pregnancy
related causes and an estimated 10 million experience injuries, infections and
disease that can cause lifelong suffering attributed to poor quality care. Client
satisfaction on health care delivery is an indication of quality care and
reported to affect health service utilization. Individuals happy with the care
received comply with services and follow up. The aim of this study was to assess
women's satisfaction with care during child birth and associated factors.
METHODS: Hospital based cross-sectional study was conducted on women delivering
their baby in April to May 2014. Systematic sampling procedure was used to select
594 eligible women, and face to face interview technique was used to collect the
data. The data were coded, entered into EPI-INFO (3.5.1) and analyzed using SPSS
version 20 software package. RESULTS: The findings of this study revealed that
the proportion of women satisfied with childbirth care service was 74.9 %.
Mothers whose age less than 20, and 20-34 years were less likely to satisfy with
the care during child birth compared to mothers whose age was above 35 years (AOR
= 0.17, 95 % CI 0.04-0.68, and AOR = 0.13.95 % CI 0.13-0.85). Besides, women who
did not attend ANC were more than 3 times likely to satisfy with care compared to
women attended ANC (AOR = 3.75, 95 % CI 1.12-12.59). Moreover, who who gave birth
for the first time, and two to five times were more than 4 times likely to
satisfy compared to women who gave birth for more than 5 times (AOR = 4.68, 95 %
CI 1.75-12.54, and AOR = 4.38, 95 % CI 1.91-12.22). CONCLUSION: Only 75 % of
women gave birth satisfied with the care they received. Moreover, age of women,
antenatal care follow-up and the number of deliveries were important predictors
of level of satisfaction. Therefore, the hospital administration and health
professionals need to offer patient oriented service to increase level of
satisfaction, as it is one of the measures of quality care.
PMID- 26427533
TI - A cross sectional study of upper extremity strength ten days after a stroke;
relationship between patient-reported and objective measures.
AB - BACKGROUND: Reduced upper extremity function early after a stroke is common, and
a combination of strength capacity and patient-reported measures contribute to
setting realistic goals. The validity of the patient's perception of upper
extremity strength in relation to objective strength assessments early after a
stroke needs to be clarified. The objective was to investigate the relationship
between perceived upper extremity strength and measured hand strength at ten days
post-stroke. METHODS: This study of 99 patients with reduced upper extremity
function at 3 days post stroke, were consecutively included from a stroke unit to
the Stroke Arm Longitudinal Study at the University of Gothenburg, (the SALGOT
study). The correlations between two questions from the Stroke Impact Scale (SIS
1a and 1b), and a dynamometer measure of hand strength values (percentage of
normative values) were investigated. In order to explain differences between the
two types of measurements, the accordance between perceived strength in a
dichotomized SIS and objective measures was explored. In SIS 1a and 1b, 1-3
points correspond to reduced strength (<80% or normative strength values). In SIS
1a and 1b, 4-5 points correspond to normal strength (>= 80% of normative strength
values). RESULTS: The correlation between the measured strength values and
perceived arm strength was rho 0.82 (p = <0.001) and with perceived grip
strength rho 0.87 (p = <0.001). Using the dichotomized SIS and the 80% cut-off
correctly classified arm strength in 81% and grip strength in 84% of the
patients, with a sensitivity of 0.86-0.87, a specificity of 0.62-0.77, positive
predicted values of 0.87-0.91 and negative predicated values of 0.64-0.67.
DISCUSSION: The discrepancy between assessed strength capacity and self-perceived
strength highlights the importance of including self-perceived assessments early
after stroke, in order to increase knowledge of a patient's awareness of
functioning or lack thereof. CONCLUSIONS: Ten days after stroke in patients
without severe cognitive disabilities, this study suggests that despite high
correlations between measures, an objective assessment of arm and hand strength
does not always reflect the patient's perspective. A combination of self-reported
and objective strength assessment is requested to enhance in setting of realistic
goals early after stroke. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01115348,
May 3, 2010.
PMID- 26427535
TI - A 16-year-old with ST elevation myocardial infarction: case report and review of
the literature.
AB - Chest pain in young adults presents a unique diagnostic challenge, placing young
patients at an increased risk to be misdiagnosed, as this patient population
typically does not demonstrate the traditional risk factors associated with
cardiovascular disease. This study details the case of a 16-year-old male who
presented with new-onset chest pain and ST elevation on electrocardiogram. His
history was unremarkable for known cardiac risk factors, but laboratory
evaluation demonstrated markedly elevated troponins and electrocardiographic
findings confirmed ST-segment elevation myocardial infarction. Coronary
angiography demonstrated 100% occlusion of the left anterior descending artery,
which was managed with percutaneous transluminal coronary angioplasty,
thrombectomy, and bare-metal stenting. The patient had an uneventful recovery.
This study examines the major causes of ST elevation myocardial infarction in
young adults and reviews the major differences between younger and older
myocardial infarction populations with emphasis on risk factor profile,
pathophysiological mechanisms, clinical presentation, angiographic findings, and
prognosis. This review highlights the need for consideration of a wide
differential in younger subsets of the population presenting with chest pain and
ST elevation. The implementation of current adult management protocols and
guidelines for ST elevation myocardial infarction should not be overlooked due to
age. Given the potential for premature death and long-term disability with
resulting individual and societal consequences, it is crucial to understand the
importance of correct diagnostic evaluation in this clinical scenario.
PMID- 26427534
TI - Gender differences in the progression of target organ damage in patients with
increased insulin resistance: the LOD-DIABETES study.
AB - BACKGROUND: The purpose of this study was to analyze the evolution of vascular,
cardiac and renal target organ damage (TOD) in patients with increased insulin
resistance over a 3.5 year follow-up and to investigate gender difference and
factors that influence its progression. METHODS: We performed a prospective
observational study involving 112 patients (71 men, 41 women) who were followed
for 3.5 years. Measurements included blood pressure, blood glucose, lipids,
smoking, body mass index (BMI) and HOMA-Ir Vascular TOD included carotid intima
media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index (ABI).
Cardiac TOD included Cornell voltage-duration product and Sokolow. Renal TOD
included creatinine, glomerular filtration and albumin/creatinine ratio. RESULTS:
The IMT increased in both genders. Each year, the IMT increased 0.005 mm in men
and 0.011 in women and the PWV 0.024 and 0.020 m/sec, respectively. The highest
increase was in women with type 2 diabetes mellitus, who had an increase in TOD
carotid (40%), PWV (24%) and renal TOD (20 %). Multiple regression analysis,
after adjusting for age and gender, showed a negative association between
duration since diabetes diagnosis and ABI (beta = -0.006; p = 0.017) and between
BMI and glomerular filtration (beta = -0.813; p = 0.014). HbA1c was positively
associated with PWV (beta = 0.501; p = 0.014). CONCLUSIONS: This study showed
that the progression of vascular and renal TOD differs by gender. The increase in
vascular and renal TOD was higher in women, especially in diabetic women. The PWV
increase showed a positive association with mean HbA1c levels during the follow
up. Glomerular filtration was associated with BMI and the ABI was associated with
duration since type 2 diabetes mellitus diagnosis. TRIAL REGISTRATION: Clinical
Trials.gov Identifier NCT01065155.
PMID- 26427536
TI - Brugia RapidTM antibody responses in communities of Indonesia in relation to the
results of 'transmission assessment surveys' (TAS) for the lymphatic filariasis
elimination program.
AB - BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis recommends the
transmission assessment survey (TAS) as the preferred methodology for determining
whether mass drug administration can be stopped in an endemic area. Because of
the limited experience available globally with the use of Brugia RapidTM tests in
conducting TAS in Brugia spp. areas, we explored the relationship between the
antibody test results and Brugia spp. infection as detected by microfilaremia in
different epidemiological settings. METHODS: The study analyzes the Brugia
RapidTM antibody responses and microfilaremia in all ages at three study sites
in: i) a district which was classified as non-endemic, ii) a district which
passed TAS, and iii) a district which failed TAS. Convenience sampling was done
in each site, in one to three purposefully selected villages with a goal of 500
samples in each district. RESULTS: A total of 1543 samples were collected from
residents in all three study sites. In the site which was classified as non
endemic and where MDA had not been conducted, 5 % of study participants were
antibody positive, none was positive for microfilaremia, and age-specific
antibody prevalence peaked at almost 8 % in the 25-34 year-old age range, with no
antibody-positive results found in children under eight years of age. In the site
that had passed TAS, 1 % of participants were antibody positive and none was
positive for microfilaremia. In the site which failed TAS, 15 % of participants
were antibody positive, 0.2 % were microfilaremic, and age-specific antibody
prevalence was highest in 6-7 year olds (30 %), but above 8 % in all age levels
above 8 years old. CONCLUSIONS: These results from districts which followed the
current WHO guidance for mapping, MDA, and implementing TAS, while providing
antibody profiles of treated and untreated populations under programmatic
settings, support the choice of antibody prevalence in the 6- and 7-year-old age
group in TAS for making stopping MDA decisions. Since only one study participant
was microfilaremic, no conclusions could be drawn about the relationship between
antibodies and microfilaremia and further longitudinal studies are required to
understand this relationship.
PMID- 26427537
TI - Comprehensive Two-Dimensional Interrogation of the Tricuspid Valve Using
Knowledge Derived from Three-Dimensional Echocardiography.
AB - BACKGROUND: Accurate identification of tricuspid valve (TV) leaflets by two
dimensional (2D) transthoracic echocardiography is difficult because of
variability in the intersection between the imaging plane and leaflets. Using
information obtained from multiplanar reconstruction (MPR) of three-dimensional
(3D) data sets, the investigators sought to define "novel" 2D views that would
allow targeted interrogation of TV leaflets using 2D transthoracic
echocardiography. METHODS: Images of the TV in the standard 2D views (apical four
chamber, right ventricular focused, right ventricular inflow, and parasternal
short axis) and 3D data sets were acquired from the same probe position in 106
adults. Three-dimensional MPR was used to determine which leaflet combination was
seen in the 2D image: anterior and septal, anterior and posterior, anterior
alone, or posterior and septal. Using this analysis, 2D landmarks were identified
to define nonstandard TV views tailored to depict specific leaflets. Two
dimensional images in these views and 3D data sets were then prospectively
collected in 54 additional patients. Three independent readers analyzed these 2D
views to determine TV leaflet combinations, and their interpretation was compared
with 3D MPR-derived reference. RESULTS: Three-dimensional MPR views made it
possible to define six nonstandard 2D views on the basis of anatomic clues and
landmarks, which consistently depicted all the aforementioned leaflet
combinations. When these six views were prospectively tested, the agreement of TV
leaflet identification against 3D MPR was excellent (kappa = 0.88, kappa = 0.93,
and kappa = 0.98). CONCLUSION: The nonstandard 2D views defined in this study
allow accurate TV leaflet identification and may thus be useful when localization
of TV leaflet pathology is clinically important.
PMID- 26427538
TI - [Endotracheal intubation using the Airtraq optical laryngoscope when the glottis
is off-center of the viewfinder: are the options of optimization exhausted?].
PMID- 26427539
TI - [Pretreatment with remifentanil protects against the reduced-intestinal
contractility related to the ischemia and reperfusion injury in rat].
AB - BACKGROUND AND OBJECTIVES: Serious functional and structural alterations of
gastrointestinal tract are observed in failure of blood supply, leading to
gastrointestinal dismotility. Activation of opioid receptors provides
cardioprotective effect against ischemia-reperfusion (I/R) injury. The aim of the
present study was to determine whether or not remifentanil could reduce I/R
injury of small intestine. METHODS: Male Wistar Albino rats were subjected to
mesenteric ischemia (30min) followed by reperfusion (3h). Four groups were
designed: sham control; remifentanil alone; I/R control; and remifentanil+I/R.
Animals in remifentanil+I/R group were subjected to infusion of remifentanil
(2ugkg(-1)min(-1)) for 60min, half of which started before inducing ischemia.
Collecting the ileum tissues, evaluation of damage was based on contractile
responses to carbachol, levels of lipid peroxidation and neutrophil infiltration,
and observation of histopathological features in intestinal tissue. RESULTS:
Following reperfusion, a significant decrease in carbachol-induced contractile
response, a remarkable increase in both lipid peroxidation and neutrophil
infiltration, and a significant injury in mucosa were observed. An average
contractile response of remifentanil+I/R group was significantly different from
that of the I/R group. Lipid peroxidation and neutrophil infiltration were also
significantly suppressed by the treatment. The tissue samples of the I/R group
were grade 4 in histopathological evaluation. In remifentanil+I/R group, on the
other hand, the mucosal damage was moderate, staging as grade 1. CONCLUSIONS: The
pretreatment with remifentanil can attenuate the intestinal I/R injury at a
remarkable degree possibly by lowering lipid peroxidation and leukocyte
infiltration.
PMID- 26427540
TI - Non-steroidal anti-inflammatory drugs and risk of heart failure exacerbation: A
systematic review and meta-analysis.
AB - BACKGROUND: The association between exacerbation of heart failure (HF) and use of
non-steroidal anti-inflammatory drugs (NSAIDs) has long been recognized but the
data on this adverse effect are limited. METHODS: To further characterize this
possible association, we conducted a systematic review and meta-analysis of
observation studies that reported odds ratio, relative risk, hazard ratio or
standardized incidence ratio comparing risk of exacerbation of HF in patients
with pre-existing HF who took NSAIDs versus non-users. Pooled risk ratios (RR)
and 95% confidence intervals for conventional NSAIDs, celecoxib and rofecoxib
were calculated using random-effect, generic inverse variance method. RESULTS:
Six studies were identified and included in our data analysis. Use of
conventional NSAIDs was associated with a significantly higher risk of
development of exacerbation of HF with the pooled RR of 1.39 (95% CI 1.20-1.62).
Elevated risk was also observed among celecoxib and rofecoxib users (RR 1.34, 95%
CI 0.98-1.85 and RR 2.04, 95% CI 1.68-2.48). The pooled RR of rofecoxib was
significantly higher than conventional NSAIDs (p=0.02). CONCLUSION: Use of NSAIDs
is associated with an increased risk of HF exacerbation among patients with pre
existing HF. The excess risk was approximately 40% for conventional NSAIDs and
celecoxib. The highest risk was observed among rofecoxib users.
PMID- 26427541
TI - Dioxygen activation in the Cu-amyloid beta complex.
AB - We investigate, by means of density-functional theory, the binding of dioxygen to
Cu(I)-amyloid beta (Abeta), one of the first steps in the oxidation of ascorbate
by dioxygen. Cu, Abeta, ascorbate and dioxygen are all present in the synapse
during neurodegeneration, when the above species can trigger an irreversible
oxidative stress inducing the eventual death of neurons. The binding of dioxygen
to Cu(I) is possible and its role in dioxygen activation of Cu ligands and of
residues in the first coordination sphere is described in atomic detail. Dioxygen
is activated when a micro-environment suitable for a square-planar Cu(2+)
coordination is present and a negatively charged group like Asp 1 carboxylate
takes part in the Cu coordination anti to O2.
PMID- 26427542
TI - Breast cancer prognosis and isolated tumor cell findings in axillary lymph nodes
after core needle biopsy and fine needle aspiration cytology: Biopsy method and
breast cancer outcome.
AB - BACKGROUND: It is unknown whether performing a core needle biopsy (CNB) to
diagnose breast cancer increases the incidence of isolated tumor cells (ITC) in
the axillary sentinel lymph nodes. METHODS: Patients diagnosed with unilateral
invasive pT1 breast cancer (<=2 cm in diameter, n = 1525) at a single center
between February 2001 and August 2005 were included in this prospective
observational cohort study. The patients were categorized into two groups
according to the type of the preoperative breast needle biopsy performed, the CNB
and the fine needle aspiration cytology (FNAC) groups, and followed up for a
median of 9.5 years after breast surgery. RESULTS: 868 (56.9%) patients had FNAC
and 657 (43.2%) CNB. In the subset of patients with no axillary metastases (pN0,
n = 1005) 70 patients had ITC, 37 (4.3%) out of the 546 patients in FNAC group
and 33 (5.0%) out of the 459 patients in the CNB group (p = 0.798). The type of
tumor biopsy did not influence breast cancer-specific survival (p = 0.461) or
local recurrence-free survival (p = 0.814) in univariable survival analyses.
Overall, survival favored the CNB group in a univariable analysis, but no
difference in survival emerged in a multivariable analysis (p = 0.718).
CONCLUSIONS: CNB was not associated with a greater incidence of ITC in axillary
lymph nodes as compared with FNAC, and did not have an adverse effect on survival
outcomes in a patient population treated with modern adjuvant therapies.
PMID- 26427543
TI - Sitagliptin and cardiovascular outcomes in diabetic patients with chronic kidney
disease after acute myocardial infarction.
PMID- 26427544
TI - Risk of major cardiovascular events in patients with hemodialysis or peritoneal
dialysis with special reference to stroke.
PMID- 26427545
TI - Identification of a conserved neutralizing linear B-cell epitope in the VP1
proteins of duck hepatitis A virus type 1 and 3.
AB - Duck virus hepatitis (DVH), mainly caused by duck hepatitis A virus (DHAV), is a
severe disease threaten to duck industry and has worldwide distribution. As the
major structural protein, the VP1 protein of DHAV is able to induce neutralizing
antibody in ducks. In this study, a monoclonal antibody (mAb) 4F8 against the
intact DHAV-1 particles was used to identify the possible epitope in the three
serotypes of DHAV. The mAb 4F8 had weak neutralizing activities to both DHAV-1
and DHAV-3, and reacted with the conserved linear B-cell epitopes of
(75)GEIILT(80) in DHAV-1 VP1 and (75)GEVILT(80) in DHAV-3 VP1 protein,
respectively, while not with DHAV-2 VP1. This was the first report about
identification of the common conserved neutralizing linear B-cell epitope of DHAV
1 and DHAV-3, which will facilitate understanding of the antigenic structure of
VP1 and the serologic diagnosis of DHAV infection.
PMID- 26427546
TI - Evaluation of in-vivo measurement errors associated with micro-computed
tomography scans by means of the bone surface distance approach.
AB - In vivo micro-computed tomography (uCT) scanning is an important tool for
longitudinal monitoring of the bone adaptation process in animal models. However,
the errors associated with the usage of in vivo uCT measurements for the
evaluation of bone adaptations remain unclear. The aim of this study was to
evaluate the measurement errors using the bone surface distance approach. The
right tibiae of eight 14-week-old C57BL/6 J female mice were consecutively
scanned four times in an in vivo uCT scanner using a nominal isotropic image
voxel size (10.4 um) and the tibiae were repositioned between each scan. The
repeated scan image datasets were aligned to the corresponding baseline (first)
scan image dataset using rigid registration and a region of interest was selected
in the proximal tibia metaphysis for analysis. The bone surface distances between
the repeated and the baseline scan datasets were evaluated. It was found that the
average (+/-standard deviation) median and 95th percentile bone surface distances
were 3.10 +/- 0.76 um and 9.58 +/- 1.70 um, respectively. This study indicated
that there were inevitable errors associated with the in vivo uCT measurements of
bone microarchitecture and these errors should be taken into account for a better
interpretation of bone adaptations measured with in vivo uCT.
PMID- 26427547
TI - Behavioral and physiological changes around estrus events identified using
multiple automated monitoring technologies.
AB - This study included 2 objectives. The first objective was to describe estrus
related changes in parameters automatically recorded by the CowManager SensOor
(Agis Automatisering, Harmelen, the Netherlands), DVM bolus (DVM Systems LLC,
Greeley, CO), HR Tag (SCR Engineers Ltd., Netanya, Israel), IceQube (IceRobotics
Ltd., Edinburgh, UK), and Track a Cow (Animart Inc., Beaver Dam, WI). This
objective was accomplished using 35 cows in 3 groups between January and June
2013 at the University of Kentucky Coldstream Dairy. We used a modified Ovsynch
with G7G protocol to partially synchronize ovulation, ending after the last
PGF2alpha injection (d 0) to allow estrus expression. Visual observation for
standing estrus was conducted for four 30-min periods at 0330, 1000, 1430, and
2200h on d 2, 3, 4, and 5. Eighteen of the 35 cows stood to be mounted at least
once during the observation period. These cows were used to compare differences
between the 6h before and after the first standing event (estrus) and the 2wk
preceding that period (nonestrus) for all technology parameters. Differences
between estrus and nonestrus were observed for CowManager SensOor minutes feeding
per hour, minutes of high ear activity per hour, and minutes ruminating per hour;
twice daily DVM bolus reticulorumen temperature; HR Tag neck activity per 2h and
minutes ruminating per 2h; IceQube lying bouts per hour, minutes lying per hour,
and number of steps per hour; and Track a Cow leg activity per hour and minutes
lying per hour. No difference between estrus and nonestrus was observed for
CowManager SensOor ear surface temperature per hour. The second objective of this
study was to explore the estrus detection potential of machine-learning
techniques using automatically collected data. Three machine-learning techniques
(random forest, linear discriminant analysis, and neural network) were applied to
automatically collected parameter data from the 18 cows observed in standing
estrus. Machine learning accuracy for all technologies ranged from 91.0 to
100.0%. When we compared visual observation with progesterone profiles of all 32
cows, we found 65.6% accuracy. Based on these results, machine-learning
techniques have potential to be applied to automatically collected technology
data for estrus detection.
PMID- 26427550
TI - Maternal mortality and severe morbidity in a migration perspective.
AB - Among migrants in high-income countries, maternal mortality and severe morbidity
generally occur more frequently as compared to host populations. There is marked
variation between groups of migrants and host countries, with much elevated risks
in some groups and no elevated risk at all in others. Those without a legal
resident permit are most vulnerable. A reason for these elevated risks could be a
different risk profile in migrants, but risk factors are unevenly distributed and
not always present. Another reason is substandard care, which is identified more
frequently in migrants, and comprises patient delays, for example, due to a lack
of knowledge about the health system in the host country, and health worker
delays, often compounded by communication barriers. Improvements in family
planning and antenatal services are needed, and audits and confidential enquiries
should be extended to include maternal morbidity and ethnic background. This
requires scientific and political efforts.
PMID- 26427551
TI - Induced pluripotent stem (iPS) cells from human fetal stem cells.
AB - Pluripotency defines the ability of stem cells to differentiate into all the
lineages of the three germ layers and self-renew indefinitely. Somatic cells can
regain the developmental potential of embryonic stem cells following ectopic
expression of a set of transcription factors or, in certain circumstances, via
modulation of culture conditions and supplementation with small molecule, that
is, induced pluripotent stem (iPS) cells. Here, we discuss the use of fetal
tissues for reprogramming, focusing in particular on stem cells derived from
human amniotic fluid, and the development of chemical reprogramming. We next
address the advantages and disadvantages of deriving pluripotent cells from fetal
tissues and the potential clinical applications.
PMID- 26427548
TI - PatchSurfers: Two methods for local molecular property-based binding ligand
prediction.
AB - Protein function prediction is an active area of research in computational
biology. Function prediction can help biologists make hypotheses for
characterization of genes and help interpret biological assays, and thus is a
productive area for collaboration between experimental and computational
biologists. Among various function prediction methods, predicting binding ligand
molecules for a target protein is an important class because ligand binding
events for a protein are usually closely intertwined with the proteins'
biological function, and also because predicted binding ligands can often be
directly tested by biochemical assays. Binding ligand prediction methods can be
classified into two types: those which are based on protein-protein (or pocket
pocket) comparison, and those that compare a target pocket directly to ligands.
Recently, our group proposed two computational binding ligand prediction methods,
Patch-Surfer, which is a pocket-pocket comparison method, and PL-PatchSurfer,
which compares a pocket to ligand molecules. The two programs apply surface patch
based descriptions to calculate similarity or complementarity between molecules.
A surface patch is characterized by physicochemical properties such as shape,
hydrophobicity, and electrostatic potentials. These properties on the surface are
represented using three-dimensional Zernike descriptors (3DZD), which are based
on a series expansion of a 3 dimensional function. Utilizing 3DZD for describing
the physicochemical properties has two main advantages: (1) rotational invariance
and (2) fast comparison. Here, we introduce Patch-Surfer and PL-PatchSurfer with
an emphasis on PL-PatchSurfer, which is more recently developed. Illustrative
examples of PL-PatchSurfer performance on binding ligand prediction as well as
virtual drug screening are also provided.
PMID- 26427549
TI - Using magnets and magnetic beads to dissect signaling pathways activated by
mechanical tension applied to cells.
AB - Cellular tension has implications in normal biology and pathology. Membrane
adhesion receptors serve as conduits for mechanotransduction that lead to
cellular responses. Ligand-conjugated magnetic beads are a useful tool in the
study of how cells sense and respond to tension. Here we detail methods for their
use in applying tension to cells and strategies for analyzing the results. We
demonstrate the methods by analyzing mechanotransduction through VE-cadherin on
endothelial cells using both permanent magnets and magnetic tweezers.
PMID- 26427552
TI - Electron transfer activity of a de novo designed copper center in a three-helix
bundle fold.
AB - In this work, we characterized the intermolecular electron transfer (ET)
properties of a de novo designed metallopeptide using laser-flash photolysis.
alpha3D-CH3 is three helix bundle peptide that was designed to contain a copper
ET site that is found in the beta-barrel fold of native cupredoxins. The ET
activity of Cualpha3D-CH3 was determined using five different photosensitizers.
By exhibiting a complete depletion of the photo-oxidant and the successive
formation of a Cu(II) species at 400 nm, the transient and generated spectra
demonstrated an ET transfer reaction between the photo-oxidant and Cu(I)alpha3D
CH3. This observation illustrated our success in integrating an ET center within
a de novo designed scaffold. From the kinetic traces at 400 nm, first-order and
bimolecular rate constants of 10(5) s(-1) and 10(8) M(-1) s(-1) were derived.
Moreover, a Marcus equation analysis on the rate versus driving force study
produced a reorganization energy of 1.1 eV, demonstrating that the helical fold
of alpha3D requires further structural optimization to efficiently perform ET.
This article is part of a Special Issue entitled Biodesign for Bioenergetics--the
design and engineering of electronic transfer cofactors, proteins and protein
networks, edited by Ronald L. Koder and J.L. Ross Anderson.
PMID- 26427553
TI - Nasal chitosan microparticles target a zidovudine prodrug to brain HIV
sanctuaries.
AB - Zidovudine (AZT) is an antiretroviral drug that is a substrate of active efflux
transporters (AETs) that extrude the drug from the central nervous system (CNS)
and macrophages, which are considered to be sanctuaries of HIV. The conjugation
of AZT to ursodeoxycholic acid is known to produce a prodrug (UDCA-AZT) that is
able to elude the AET systems, indicating the potential ability of this prodrug
to act as a carrier of AZT in the CNS and in macrophages. Here, we demonstrate
that UDCA-AZT is able to permeate and remain in murine macrophages with an
efficiency twenty times higher than that of AZT. Moreover, we propose the nasal
administration of this prodrug in order to induce its uptake into the CNS.
Chitosan chloride-based microparticles (CP) were prepared by spray-drying and
were characterized with respect to size, morphology, density, water uptake and
the dissolution profile of UDCA-AZT. The CP sample was then nasally administered
to rats. All in vitro and in vivo measurements were also performed for a CP
parent physical mixture. The CP sample was able to increase the dissolution rate
of UDCA-AZT and to reduce water uptake with respect to its parent physical
mixture, inducing better uptake of UDCA-AZT into the cerebrospinal fluid of rats,
where the prodrug can act as an AZT carrier in macrophages.
PMID- 26427554
TI - Antiretroviral drugs do not interfere with bryostatin-mediated HIV-1 latency
reversal.
AB - Although an effective combination of antiretroviral therapy (cART) controls HIV-1
viraemia in infected patients, viral latency established soon after infection
hinders HIV-1 eradication. It has been shown that bryostatin-1 (BRY) inhibits HIV
infection in vitro and reactivates the latent virus through the protein kinase C
NF-kappaB pathway. We determined the in vitro potential effect of BRY in
combination with currently used antiretroviral drugs. BRY alone or in combination
with maraviroc (MVC)/Atripla (ATP) was tested for its capacity to reactivate
latent virus and inhibit new infections. JLTRG-R5 cells and two latent HIV-1
infected cell lines, J89GFP and THP89GFP, were used as latency models. To
quantify HIV infection, the reporter cell line TZM-bl was used. We found that BRY
reactivates HIV-1 even in combination with MVC or ATP. Antiretroviral
combinations with BRY do not interfere with BRY activity (i.e., the reactivation
of latently infected cells) or with the antiviral activity of antiretroviral
drugs. In addition, BRY-mediated down-modulation of surface CD4 and CXCR4 was not
affected when it was used in combination with other antiretrovirals, and no
hyperactivation or high-proliferation effects were observed in primary T cells.
Moreover, the BRY treatment was able to reactivate HIV-1 in CD4+ T cells from HIV
1-infected patients under cART. Thus, we propose the use of BRY to purge the
viral reservoir and recommend its combination with current antiretroviral
treatments.
PMID- 26427555
TI - Molecular simulations of glycolipids: Towards mammalian cell membrane models.
AB - Glycolipids are key components of mammalian cell membranes, influencing a diverse
range of cellular functions. For example, a number of receptor tyrosine kinases,
including the epidermal growth factor receptor (EGFR), are allosterically
regulated by the glycolipid monosialodihexosylganglioside (GM3). Recent advances
in molecular dynamics methods, especially the development of coarse-grained
models, have enabled simulations of increasingly complex models of cell
membranes. We demonstrate these methodological developments via a case study of a
coarse-grained model for the ganglioside GM3. This glycolipid is included in
simulations of a mixed lipid bilayer model reflecting the compositional
complexity of a mammalian cell membrane. The resultant membrane model is used to
simulate the interactions of GM3 with the transmembrane domain of the EGFR.
PMID- 26427556
TI - Changing in lipid profile induced by the mutation of Foxn1 gene: A lipidomic
analysis of Nude mice skin.
AB - Nude mice carry a spontaneous mutation affecting the gene Foxn1 mainly expressed
in the epidermis. This gene is involved in several skin functions, especially in
the proliferation and the differentiation of keratinocytes which are key cells of
epithelial barrier. The skin, a protective barrier for the body, is essentially
composed of lipids. Taking into account these factors, we conducted a lipidomic
study to search for any changes in lipid composition of skin possibly related to
Foxn1 mutation. Lipids were extracted from skin biopsies of Nude and BALB/c mice
to be analyzed by liquid chromatography coupled to a high resolution mass
spectrometer (HRMS). Multivariate and univariate data analyses were carried out
to compare lipid extracts. Identification was performed using HRMS data,
retention time and mass spectrometry fragmentation study. These results indicate
that mutation of Foxn1 leads to significant modifications in the lipidome in Nude
mice skin. An increase in cholesterol sulfate, phospholipids, sphingolipids and
fatty acids associated with a decrease in glycerolipids suggest that the lipidome
in mice skin is regulated by the Foxn1 gene.
PMID- 26427557
TI - Kinetics of quadruplex to duplex conversion.
AB - The equilibrium between G-quadruplex (G4) and duplex DNA structures is a
fundamental question whenever G4 are considered within a genomic context. In this
study, we performed a detailed thermodynamic and kinetic analysis of this
equilibria using a new fast and high throughput technique for the screening of G4
structures. This assay examines the isothermal stability of G-quadruplexes in the
presence of complementary strands monitoring the unwinding process by
fluorescence techniques. Unlabelled G4 structures were used in order to avoid any
thermodynamic effect that fluorophores could have on the G4 stability. The assay
was applied to investigate the effect that flanking sequences can have on the
thermodynamic stability of the quadruplex motifs. Interestingly, the presence of
adjacent bases to the G4 structure facilitates the recognition of the
complementary strand accelerating the G4 unfolding reaction. The simplicity of
the systems employed and the use of fluorescence emission allowed the use of high
throughput techniques and to monitor the opening reaction in real time in a
"pseudo" label-free method. This G4 opening reaction may be easily implemented as
a new isothermal assay for the screening of G4 structures, G4 ligands or G4
binding proteins.
PMID- 26427558
TI - Initiation of phospholipomannan beta-1,2 mannosylation involves Bmts with
redundant activity, influences its cell wall location and regulates beta-glucans
homeostasis but is dispensable for Candida albicans systemic infection.
AB - Pathogenic and non-pathogenic fungi synthesize glycosphingolipids, which have a
crucial role in growth and viability. Glycosphingolipids also contribute to
fungal-associated pathogenesis. The opportunistic yeast pathogen Candida albicans
synthesizes phospholipomannan (PLM), which is a glycosphingolipid of the
mannosylinositol phosphorylceramide family. Through its lipid and glycan
moieties, PLM contributes to the initial recognition of the yeast, causing immune
system disorder and persistent fungal disease through activation of host
signaling pathways. The lipid moiety of PLM activates the deregulation signaling
pathway involved in yeast phagocytosis whereas its glycan moiety, composed of
beta-1,2 mannosides (beta-Mans), participates to inflammatory processes through a
mechanism involving Galectin-3. Biosynthesis of PLM beta-Mans involves two beta
1,2 mannosyltransferases (Bmts) that initiate (Bmt5) and elongate (Bmt6) the
glycan chains. After generation of double bmtsDelta mutants, we show that Bmt5
has redundant activity with Bmt2, which can replace Bmt5 in bmt5Delta mutant. We
also report that PLM is located in the inner layer of the yeast cell wall. PLM
seems to be not essential for systemic infection of the yeast. However, defect of
PLM beta-mannosylation increases resistance of C. albicans to inhibitors of beta
glucans and chitin synthesis, highlighting a role of PLM in cell wall
homeostasis.
PMID- 26427559
TI - [Bloodstream infection due to Campylobacter fetus subspecies fetus and skin
involvement: A case series of three patients].
AB - INTRODUCTION: Among the species of Campylobacter, C. fetus subspecies fetus is
characterized by extra-intestinal manifestations, including bloodstream and
cardiovascular infections, occurring preferentially in the context of
immunosuppression. The cutaneous lesions are rarely described but may be
underestimated. CASE REPORTS: We report on 3 cases of cellulitis with bloodstream
infection due to Campylobacter fetus subspecies fetus, without cardiovascular
infection in a 72- and 85-year-old women, respectively, and a 79-year-old man.
Outcome was successful in all 3 cases after prolonged amoxicillin-clavulanic acid
treatment, without relapse. CONCLUSION: C. fetus subspecies fetus is rarely
associated with skin and soft tissue infections. Cardiovascular complications may
be searched in such context.
PMID- 26427560
TI - Influence of remission and its duration on development of early microvascular
complications in young adults with type 1 diabetes.
AB - INTRODUCTION: Prevalence of partial remission ranges between 20% and 80% in the
initial course of type 1 diabetes. In this phase of the disease, a substantial
insulin secretion contributes to good metabolic control. The aim of the study was
to determine the association between presence of partial remission and occurrence
of microangiopathy complications in type 1 diabetes. MATERIAL AND METHODS: Ninety
eight consecutive patients with newly diagnosed type 1 diabetes were asked to
participate in a cohort study. Partial remission was defined as the time in which
all of the following criteria were met: HbA1c below 6.5% (48mmol/mol), daily
insulin requirement below 0.3 U/kg body weight and serum Cpeptide concentration
above 0.5ng/ml. Patients were divided into those who were in remission at any
time during follow-up (remitters) and non-remitters. After 7years of follow-up,
the occurrence of microangiopathy complications was analyzed. In statistical
analysis, Mann-Whitney test, chi(2) test and Fisher test were used for analysis
between groups. We applied a Cox's multivariate regression model and univariate
regression method. P<0.05 was considered statistically significant. RESULTS: In
univariate logistic regression, a significant association was found between
absence of remission and occurrence of at least one microvascular complication.
In the Cox proportional hazards regression model that included clinically
significant parameters at diagnosis (presence of ketoacidosis, cigarette smoking
and HbA1c value) as covariates, absence of remission was associated with
occurrence of chronic complications of diabetes at 7years [HR: 3.65 (95% CI 1.23
4.56), p=0.04]. In non-remitters, higher incidence of at least one microvascular
complication (46.4% vs. 7.6%), higher incidence of retinopathy (42.8% vs. 5.7%),
and neuropathy (21.4% vs. 1.9%) was found. CONCLUSIONS: Occurrence of partial
remission of diabetes is associated with a reduced risk of chronic microvascular
complications at 7-year follow-up.
PMID- 26427561
TI - Evaluation of a supervised multi-modal physical exercise program for prostate
cancer survivors in the rehabilitation phase: Rationale and study protocol of the
ProCaLife study.
AB - BACKGROUND: After treatment for localized prostate cancer, many survivors
experience severe physical and psychological/psychosocial impairments, such as
urinary incontinence, erectile dysfunction, fatigue, depressive symptoms and
decreased physical functioning. Physical activity and exercise can positively
influence such side effects and improve quality of life. However, the majority of
prostate cancer survivors are not physically active. Thus, supportive
interventions, such as supervised exercise programs, are necessary. But
particularly in the post-treatment phase, infrastructure and resources are
limited and specific exercise recommendations for prostate cancer survivors do
not yet exist. METHODS/DESIGN: The ProCaLife study is a quasi-randomized
controlled intervention trial evaluating a specific 26-week physical exercise
program for prostate cancer survivors in the rehabilitation phase following
medical treatment. Participants are assigned to one of two intervention groups
(supervised multi-modal physical exercise including or not including further
behavior-oriented techniques) or a control group (not receiving any supervised
intervention). Exercise sessions are performed twice weekly and contain specific
aerobic, strengthening, flexibility, balance, relaxation and pelvic
floor/sphincter exercises as well as mixed games. Behavior-oriented techniques
include physical activity-related knowledge transfer and barriers management. The
primary endpoint quality of life and secondary psychological/psychosocial,
urological, physical fitness and physical activity outcomes are assessed at pre
intervention, post-intervention and follow-up time points. DISCUSSION/CONCLUSION:
By evaluating a specific supervised multi-modal physical exercise program, the
ProCaLife study contributes to identify effective forms of physical exercise for
prostate cancer survivors in the rehabilitation phase. This is of great
importance for establishing specific exercise recommendations which are missing
so far.
PMID- 26427562
TI - Connect for Health: Design of a clinical-community childhood obesity intervention
testing best practices of positive outliers.
AB - BACKGROUND: The Connect for Health study is designed to assess whether a novel
approach to care delivery that leverages clinical and community resources and
addresses socio-contextual factors will improve body mass index (BMI) and family
centered, obesity-related outcomes of interest to parents and children. The
intervention is informed by clinical, community, parent, and youth stakeholders
and incorporates successful strategies and best practices learned from 'positive
outlier' families, i.e., those who have succeeded in changing their health
behaviors and improve their BMI in the context of adverse built and social
environments. DESIGN: Two-arm, randomized controlled trial with measures at
baseline and 12 months after randomization. PARTICIPANTS: 2-12 year old children
with overweight or obesity (BMI >= 85th percentile) and their parents/guardians
recruited from 6 pediatric practices in eastern Massachusetts. INTERVENTION:
Children randomized to the intervention arm receive a contextually-tailored
intervention delivered by trained health coaches who use advanced geographic
information system tools to characterize children's environments and neighborhood
resources. Health coaches link families to community-level resources and use
multiple support modalities including text messages and virtual visits to support
families over a one-year intervention period. The control group receives enhanced
pediatric care plus non-tailored health coaching. MAIN OUTCOME MEASURES: Lower
age-associated increase in BMI over a 1-year period. The main parent- and child
reported outcome is improved health-related quality of life. CONCLUSIONS: The
Connect for Health study seeks to support families in leveraging clinical and
community resources to improve obesity-related outcomes that are most important
to parents and children.
PMID- 26427565
TI - Renal Tumour Biopsy--A New Standard of Care?
PMID- 26427564
TI - The Surgical Learning Curve for One-stage Anterior Urethroplasty: A Prospective
Single-surgeon Study.
AB - BACKGROUND: The learning process for one-stage anterior urethroplasty has never
been addressed before. OBJECTIVE: To evaluate the surgical learning curve for one
stage anterior urethroplasty. DESIGN, SETTING, AND PARTICIPANTS: Data from 641
consecutive patients treated with one-stage urethroplasty for urethral stricture
were collected prospectively. All the procedures were performed by a single
surgeon between 1994 and 2014. INTERVENTION: One-stage anterior urethroplasty
using substitute tissues. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The
outcome was treatment failure, defined as any postoperative instrumentation
needed including dilation. Surgeon experience was coded as the total number of
one-stage urethroplasties performed by the surgeon before the operation.
Multivariable Cox regression analysis was used to evaluate the association
between surgeon experience and treatment failure. Covariates consisted of age,
body mass index, smoking history (no, yes, ex-smoker), diabetes history (no or
yes), previous surgical treatments (no or yes), stricture length, and stricture
site (bulbar, penile, panurethral). RESULTS AND LIMITATIONS: Overall, 546
patients (85%) were treated with one-stage oral mucosa urethroplasty; penile skin
or skin flap was used in 95 patients (15%). Median follow-up among patients who
did not experience surgical failure was 69 mo (interquartile range: 35-118). The
failure-free survival at 5 yr was 77% (95% confidence interval [CI], 74-81). At
multivariable analysis, surgeon experience was significantly associated with a
lower probability of treatment failure (hazard ratio per 20 procedures: 0.98; 95%
CI, 0.97-0.99; p=0.008). The surgical learning curve appeared lengthened, without
reaching a plateau even after 600 procedures. CONCLUSIONS: In this single-surgeon
analysis, surgical experience has a significant impact on the probability of
treatment success for one-stage urethroplasty. Better results are achieved only
after a long learning curve that may not be justifiable for late-career and low
volume surgeons. PATIENT SUMMARY: The probability of surgical success after one
stage urethroplasty is importantly influenced by surgeon experience. Better
results are achieved only after a very long learning process.
PMID- 26427563
TI - Impact of increasing physical activity on cognitive functioning in breast cancer
survivors: Rationale and study design of Memory & Motion.
AB - INTRODUCTION: Many breast cancer survivors experience problems with cognitive
functioning that can persist years after treatment. Increasing physical activity
has been shown to improve cognitive functioning in healthy and cognitively
impaired adults, but has not yet been tested in cancer survivors. The primary aim
of this randomized controlled trial is to examine the effects of a 3-month
physical activity intervention compared to a waitlist Control arm on
neuropsychological outcomes and subjective cognitive concerns in breast cancer
survivors. METHODS: Eighty sedentary breast cancer survivors, self-reporting
difficulties with cognition, will be randomized into an Exercise arm or Control
arm. The Exercise arm includes an activity tracker (i.e., a Fitbit), phone calls,
plus tailored and non-tailored email content. The Control arm will receive emails
on women's health topics on the same schedule as the Exercise arm. Assessments
conducted at baseline and 3 months include: neuropsychological testing, cognitive
concerns and other aspects of quality of life, and 7 days of a hip-worn
accelerometer. Participants will also provide fasting blood draws to assess brain
derived neurotropic factor, Insulin-like growth factor 1, insulin resistance, and
C-reactive protein. Primary and secondary outcomes are changes in
neuropsychological testing and cognitive concerns. Biomarkers will be examined to
further understand the underlying relationship between physical activity and
cognition. CONCLUSION: The Memory & Motion study is designed to test whether
increasing physical activity can improve cognitive functioning in breast cancer
survivors. Results from this study could be used to guide development of
interventions to improve cognitive functioning in breast cancer survivors.
PMID- 26427566
TI - PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2.
AB - The Prostate Imaging - Reporting and Data System Version 2 (PI-RADSTM v2) is the
product of an international collaboration of the American College of Radiology
(ACR), European Society of Uroradiology (ESUR), and AdMetech Foundation. It is
designed to promote global standardization and diminish variation in the
acquisition, interpretation, and reporting of prostate multiparametric magnetic
resonance imaging (mpMRI) examination, and it is based on the best available
evidence and expert consensus opinion. It establishes minimum acceptable
technical parameters for prostate mpMRI, simplifies and standardizes terminology
and content of reports, and provides assessment categories that summarize levels
of suspicion or risk of clinically significant prostate cancer that can be used
to assist selection of patients for biopsies and management. It is intended to be
used in routine clinical practice and also to facilitate data collection and
outcome monitoring for research.
PMID- 26427567
TI - What is the Contribution of Genetics to Periodontal Risk?
AB - This review addresses the multicausal etiology of periodontitis, in which genetic
factors play a role. The various proposed causes for periodontitis always work
simultaneously, but the relative contribution of each of these varies from case
to case. We are still at an early stage to identify the genes involved, in
comparison with other chronic diseases. To date, the genetic variations firmly
and repeatedly associated with periodontitis in some populations are found within
the following genes: ANRIL, COX2, IL1, IL10, DEFB1, whereas many other proposed
periodontitis candidate genes have not been firmly proven or replicated.
PMID- 26427568
TI - What is the Proper Sample Size for Studies of Periodontal Treatment?
AB - Small sample sizes are a common problem in biomedical research, and the
periodontal literature is no exception. It is a problem leading to not only
reduced statistical power but also an inappropriate statistical inference of a
treatment effect. Using statistical methods with an insufficient sample size may
give rise to an increased chance of falsely detecting treatment efficacy. This
article provides some guidelines to cope with the small sample size problem. The
authors discuss adequate sample sizes in several statistical tests and then
suggest alternative statistical methods that are valid with a small sample size.
PMID- 26427569
TI - Can Chemical Mouthwash Agents Achieve Plaque/Gingivitis Control?
AB - Also note that structured abstracts are not allowed per journal style: What is
the effect of a mouthwash containing various active chemical ingredients on
plaque control and managing gingivitis in adults based on evidence gathered from
existing systematic reviews? The summarized evidence suggests that mouthwashes
containing chlorhexidine(CHX) and essential oils (EO) had a large effect
supported by a strong body of evidence. Also there was strong evidence for a
moderate effect of cetylpyridinium chloride(CPC). Evidence suggests that a CHX
mouthwash is the first choice, the most reliable alternative is EO. No difference
between CHX and EO with respect to gingivitis was observed.
PMID- 26427570
TI - Is Photodynamic Therapy an Effective Treatment for Periodontal and Peri-Implant
Infections?
AB - Antimicrobial photodynamic therapy (PDT) has attracted much attention for the
treatment of pathogenic biofilm associated with peridontitis and peri
implantitis. However, data from randomized controlled clinical studies (RCTs) are
limited and, to some extent, controversial, making it difficult to provide
appropriate recommendations. Therefore, the aims of the present study were (a) to
provide an overview on the current evidence from RCTs evaluating the potential
clinical benefit for the additional use of PDT to subgingival mechanical
debridement (ie, scaling and root planing) alone in nonsurgical periodontal
therapy; and (b) to provide clinical recommendations for the use of PDT in
periodontal practice.
PMID- 26427572
TI - Do Mobility and Occlusal Trauma Impact Periodontal Longevity?
AB - The impact of tooth mobility and occlusal trauma (OT) on periodontal bone loss
and need for therapy has been debated for many years. This paper summarizes the
relevant literature reported in three Dental Clinics of North America articles in
the late 1990s, and adds newer information from the 2000s. Principle findings
indicate that strong evidence of mobility and OT impacting tooth longevity is
lacking, but reducing inflammation in the surrounding periodontium remains a
critical treatment. Occlusal therapy when mobility is increasing, comfort or
function are compromised, or periodontal regeneration procedures are planned
should be considered.
PMID- 26427571
TI - Is Radiologic Assessment of Alveolar Crest Height Useful to Monitor Periodontal
Disease Activity?
AB - The mainstay of periodontal assessment is clinical probing. Radiographic
assessment provides quantitative information on the status of tooth-supporting
bone. This article reviews methods to assess periodontal structures, including
basic radiograph acquisition, assessment of alveolar crest levels, and typical
patterns of bone loss. Computer technology to objectively assess loss of alveolar
crest from radiographs is reviewed. Developments in computer-assisted
quantitation of alveolar crest height are described. Although probing
measurements continue to be viewed as more practical than radiographic
measurements, radiographic assessment can be made quantitative and is likely
easier and more precise than probing for routine assessment of periodontal
disease activity.
PMID- 26427573
TI - Does Treatment of Periodontal Disease Influence Systemic Disease?
AB - Periodontal diseases are the most common human diseases globally, with gingivitis
affecting up to 90% and periodontitis affecting 50% of adults. Tooth enamel is
the only nonshedding tissue in the human body. In the absence of proper oral
hygiene measures, microbial biofilm (dental plaque) develops on the teeth to
include more than 700 different bacterial species, along with viruses, fungi,
archea, and parasites. With time, ecological imbalances promote the growth of
selected commensal species that induce host inflammatory pathways resulting in
tissue destruction, including ulceration of the periodontal epithelium.
PMID- 26427575
TI - Unanswered Questions: Can Bone Lost from Furcations Be Regenerated?
AB - Periodontal regeneration-treatment that results in new alveolar bone, cementum,
and a functional periodontal ligament-is successful in class II furcation
defects. This article examines one aspect of periodontal regeneration-alveolar
bone growth in furcation defects-in trying to answer the question, Can bone lost
from furcations be regenerated? The best evidence for bone growth is histology
but there is limited histologic evidence for bone growth in human furcation
defects. There is more evidence from intraoperative measurements for hard tissue
growth in treated furcation defects, but the nature of the hard tissue needs to
be determined histologically.
PMID- 26427574
TI - Should Antibiotics Be Prescribed to Treat Chronic Periodontitis?
AB - Although scaling and root planing is a cost-effective approach for initial
treatment of chronic periodontitis, it fails to eliminate subgingival pathogens
and halt progressive attachment loss in some patients. Adjunctive use of systemic
antibiotics immediately after completion of scaling and root planing can enhance
the degree of clinical attachment gain and probing depth reduction provided by
nonsurgical periodontal treatment. This article discusses the rationale for
prescribing adjunctive antibiotics, reviews the evidence for their effectiveness,
and outlines practical issues that should be considered before prescribing
antibiotics to treat chronic periodontitis.
PMID- 26427576
TI - Can Periimplantitis Be Treated?
AB - Over the past few decades, dental implants have been found to have high
predictability and survival rates because of improvements in knowledge, clinical
expertise, and implant designs. As such, dental implants are frequently
integrated in the clinical management of fully or partially edentulous patients.
It is prudent to realize that despite the high early survival rates, dental
implants do have their fair share of long-term esthetic, biological, and
mechanical complications. Therefore, this paper aims to review the current
evidence on the management of peri-implant diseases in an attempt to answer the
following question: Can periimplantitis be treated?
PMID- 26427577
TI - Does Gingival Recession Require Surgical Treatment?
AB - Gingival recession represents a clinical condition in adults frequently
encountered in the general dental practice. Clinicians often face dilemmas of
whether or not to treat such a condition surgically. An initial condensed
literature search was performed using a combination of gingival recession and
surgery controlled terms and keywords. An analysis of the search results
highlights the limited understanding of the factors that guide the treatment of
gingival recession. Understanding the cause, prognosis, and treatment of gingival
recession continues to offer many unanswered questions and challenges in
periodontics as we strive to provide the best care possible for our patients.
PMID- 26427578
TI - Unanswered Questions in Periodontology.
PMID- 26427579
TI - Incidence of Neutropenia With Valproate and Quetiapine Combination Treatment in
Subjects With Acquired Brain Injuries.
AB - OBJECTIVE: To investigate whether the incidence of neutropenia was higher in
subjects who received a combination treatment with valproate and quetiapine than
in those who were administered monotherapy. DESIGN: Retrospective cohort study.
SETTING: Rehabilitation department of a university hospital. PARTICIPANTS:
Patients with acquired brain injuries who had taken valproate for seizures or
quetiapine for delirium for >7 days (N=101). Data were extracted from electronic
medical records of the hospital. INTERVENTIONS: Not applicable. MAIN OUTCOME
MEASURES: Incidence of neutropenia (absolute neutrophil count<2000 cells/MUL) was
elicited from the weekly complete blood cell records for 71.07+/-43.71 days of
observation. The odds ratio for neutropenia development was calculated and
adjusted for variables that showed significant differences between patients with
or without neutropenia. RESULTS: The incidence of neutropenia was significantly
higher in the group receiving the combination treatment than in those receiving
the monotherapy (32.26% vs 12.90%, adjusted P=.036), despite a lack of any
differences in the daily doses of the medications. Coadministration of quetiapine
and valproate was the predictor of neutropenia development when age, body weight,
and underlying diseases were adjusted in the logistic regression model (odds
ratio=3.749; 95% confidence interval, 1.161-12.099; P=.027). CONCLUSIONS:
Administration of quetiapine together with valproate in patients with acquired
brain injury could increase the incidence of medication-induced neutropenia.
PMID- 26427580
TI - Facing our future.
PMID- 26427581
TI - Ramelteon-induced nightmares: A case report.
AB - Ramelteon is the only FDA-approved melatonin agonist for treatment of insomnia.
It acts on melatonin MT1 and MT2 receptors. We describe a case of a patient who
was prescribed ramelteon for insomnia disorder. Shortly after initiation of
ramelteon, he described vivid nightmares leading to discontinuation of ramelteon.
The nightmares ameliorated with ramelteon discontinuation. Ramelteon is well
tolerated with a favorable side-effect profile. No documented cases of nightmares
secondary to ramelteon use were found in the literature. The effects of ramelteon
on rapid eye movement sleep, the stage of sleep where dreams occur, need to be
further explored.
PMID- 26427582
TI - Pervasive refusal syndrome: A misnomer for catatonia.
PMID- 26427583
TI - Audiograms, gap detection thresholds, and frequency difference limens in
cannabinoid receptor 1 knockout mice.
AB - The cannabinoid receptor 1 (CB1R) is found at several stages in the auditory
pathway, but its role in hearing is unknown. Hearing abilities were measured in
CB1R knockout mice and compared to those of wild-type mice. Operant conditioning
and the psychophysical Method of Constant Stimuli were used to measure
audiograms, gap detection thresholds, and frequency difference limens in trained
mice using the same methods and stimuli as in previous experiments. CB1R knockout
mice showed deficits at frequencies above 8 kHz in their audiograms relative to
wild-type mice. CB1R knockouts showed enhancements for detecting gaps in low-pass
noisebursts relative to wild-type mice, but were similar for other noise
conditions. Finally, the two groups of mice did not differ in their frequency
discrimination abilities as measured by the frequency difference limens task.
These experiments suggest that the CB1R is involved in auditory processing and
lay the groundwork for future physiological experiments.
PMID- 26427584
TI - p11 modulates calcium handling through 5-HT4R pathway in rat ventricular
cardiomyocytes.
AB - BACKGROUND: The role of the serotonin receptor 4 (5-HT4R) pathway in cardiac
excitation-contraction coupling (ECC) remains unclear. In the brain, induction of
the calcium (Ca(2+))-binding protein p11 enhances 5-HT4R translocation and
signaling and could therefore be considered as a modulator of the 5-HT4R pathway
in the myocardium. p11 expression is increased by brain-derived neurotrophic
factor (BDNF) or antidepressant drugs (imipramine). Thus, we investigated whether
p11 regulates the 5-HT4R pathway in the heart in physiological conditions or
under pharmacological induction and the effects on calcium handling. METHODS AND
RESULTS: p11 expression was induced in vivo in healthy Wistar rats by imipramine
(10 mg/kg/21 days) and in vitro in left ventricular cardiomyocytes exposed to
BDNF (50 ng/ml/8h). Cell shortening and real-time Ca(2+) measurements were
processed on field-stimulated intact cardiomyocytes with the selective 5-HT4R
agonist, prucalopride (1 MUM). Both imipramine and BDNF-induced cardiomyocyte p11
expression unmasked a strong response to prucalopride characterized by an
increase of both cell shortening and Ca(2+) transient amplitude compared to basal
prucalopride associated with a high propensity to trigger diastolic Ca(2+)
events. Healthy rats treated with BDNF (180 ng/day/14 days) exhibited a sustained
elevated heart rate following a single injection of prucalopride (0.1 mg/kg)
which was not observed prior to treatment. CONCLUSIONS: We have identified a
novel role for p11 in 5-HT4R signaling in healthy rat ventricular cardiomyocytes.
Increased p11 expression by BDNF and imipramine unraveled a 5-HT4R-mediated
modulation of cardiac Ca(2+) handling and ECC associated with deleterious Ca(2+)
flux disturbances. Such mechanism could partly explain some cardiac adverse
effects induced by antidepressant treatments.
PMID- 26427585
TI - Acute liver failure during hepatitis C treatment with sofosbuvir and ledipasvir.
PMID- 26427586
TI - Circulatory response to volume expansion and transjugular intrahepatic
portosystemic shunt in refractory ascites: Relationship with diastolic
dysfunction.
AB - BACKGROUND: Cirrhotic cardiomyopathy may lead to heart failure in stressful
circumstances, such as after transjugular intrahepatic portosystemic shunt (TIPS)
placement. AIM: To examine whether acute volume expansion predicts haemodynamic
changes after TIPS and elicits signs of impending heart failure. METHODS: We
prospectively evaluated refractory ascites patients (group A) and compensated
cirrhotics (group B), who underwent echocardiography, NT-proBNP measurement, and
heart catheterization before and after volume load; group A repeated measurements
after TIPS. RESULTS: 15 patients in group A (80% male; 54+/-12.4 years) and 8 in
group B (100% male; 56+/-6.2 years) were enrolled. Echocardiography disclosed
diastolic dysfunction in 30% and 12.5%, respectively. In group A, volume load and
TIPS induced a significant increase in right atrial, mean pulmonary, capillary
wedge pressure and cardiac index, and a decrease in systemic vascular resistance
(respectively, 4.7+/-2.8 vs. 9.9+/-3.6 mmHg; 13.3+/-3.5 vs. 21.9+/-5.9 mmHg;
8.3+/-3.4 vs. 15.4+/-4.7 mmHg; 3.7+/-0.7 vs. 4.6+/-11 t/min/m2; 961+/-278 vs.
767+/-285 dynscm(-5); and 10.1+/-3.3 vs. 14.2+/-3.4 mmHg; 17.5+/-4 vs. 25.2+/-4.2
mmHg; 12.3+/-4 vs. 19.3+/-3.4 mmHg; 3.4+/-0.8 vs. 4.5+/-0.91l t/min/m2; 779+/-62
vs. 596+/-199 dynscm(-5), p<0.001 for all pairs). At 24h, cardiopulmonary
pressures returned towards baseline. CONCLUSIONS: Acute volume expansion
predicted haemodynamic changes immediately after TIPS. All patients had adequate
haemodynamic adaptation to TIPS; none developed signs of heart failure.
PMID- 26427587
TI - Reinfusion of highly purified CD133+ bone marrow-derived stem/progenitor cells in
patients with end-stage liver disease: A phase I clinical trial.
AB - BACKGROUND: Bone marrow stem/progenitor cells seem to be effective in liver
regeneration after tissue injury. AIM: To evaluate the feasibility and safety of
the mobilization and reinfusion of CD133+ stem/progenitor cells in patients with
end-stage liver disease. METHODS: Autologous CD133+ stem/progenitor cells,
mobilized with granulocyte-colony stimulating factor, were collected by
leukapheresis and reinfused at increasing doses through the hepatic artery
starting from 5*10(4)/kg up to 1*10(6)/kg. RESULTS: 16 subjects with Model for
End-stage Liver Disease (MELD) score between 17 and 25 were enrolled, 14
mobilized an adequate number of CD133+ stem/progenitor cells and 12 were
reinfused. No severe adverse events related to the procedure were reported. MELD
score significantly worsened during mobilization in Child Turcotte Pugh-C
patients. A significant improvement of liver function was observed 2 months after
reinfusion (MELD 19.5 vs. 16; P=0.045). Overall, 5 patients underwent liver
transplantation within 12 months from reinfusion and 2 died because of
progressive liver failure. CONCLUSIONS: CD133+ stem/progenitor cells reinfusion
in patients with end-stage liver disease is feasible and safe. A worsening of
liver function was observed during mobilization in Child Turcotte Pugh-C
patients. The temporary improvement of MELD score after reinfusion suggests that
stem cells therapy may be a "bridge to transplant" approach for these patients.
PMID- 26427588
TI - Failure to Improve the Oxygenation Index Is a Useful Predictor of Therapy Failure
in Acute Respiratory Distress Syndrome Clinical Trials.
AB - OBJECTIVE: Acute respiratory distress syndrome trials powered for mortality
require significant resources, limiting the number of evaluable therapies.
Validation of intermediate endpoints would enhance the feasibility of testing
novel acute respiratory distress syndrome therapies in pilot studies and
potentially reduce the frequency of failed large clinical trials. We sought to
determine whether a change in the oxygenation index over the first 7 days of
acute respiratory distress syndrome could discriminate between therapies likely
or unlikely to show benefit in larger clinical trials. DESIGN: A derivation
cohort from three acute respiratory distress syndrome studies was used to
estimate the 7-day change in oxygenation index. Receiver operating characteristic
curves were used to calculate optimal thresholds and predictability of the change
in oxygenation index for 28-day mortality and ventilator-free days. The
thresholds were then validated in two cohorts. Then, for each individual acute
respiratory distress syndrome study, the threshold 7-day oxygenation index change
was tested as an outcome measure and compared with mortality and ventilator-free
days as reported in the original study. SETTING: Medical ICUs. PATIENTS: Acute
respiratory distress syndrome patients. INTERVENTIONS: Various. MEASUREMENTS AND
MAIN RESULTS: Change in oxygenation index, 28-day mortality, and ventilator-free
days. In the derivation cohort, the mean 7-day oxygenation index improved by 4.2
(+/- 11.7) in 28-day survivors compared with an increase of 2.4 (+/- 11.6) in 28
day nonsurvivors (p < 0.001). The mean 7-day oxygenation index decreased by 5.9
(+/- 8.4) in patients with more than 14 ventilator-free days, compared with a
decrease of 1.9 (+/- 12.4) among those with less than 14 ventilator-free days (p
= 0.001). The optimal 7-day oxygenation index threshold for predicting mortality
was an increase of 1.71 and for predicting less than 14 ventilator-free days, a
decrease of 2.34. When used as a surrogate endpoint, the optimal 7-day
oxygenation index change closely approximated mortality and ventilator-free day
outcomes in three Acute Respiratory Distress Syndrome Network studies used for
the derivation cohort and a distinct study used for validation. The change in
oxygenation index was a poor predictor of individual patient outcome.
CONCLUSIONS: Failure to meet a threshold improvement in the oxygenation index
over the first 7 days of therapy can be used to identify therapies unlikely to
succeed in subsequent trials powered for mortality and ventilator-free days. By
reducing trial time and costs, use of the 7-day oxygenation index change as an
intermediate endpoint could increase the number of clinical trials of promising
therapies for acute respiratory distress syndrome and reduce the number of large
scale trials of therapies unlikely to be of benefit.
PMID- 26427589
TI - Systemic Corticosteroids and Transition to Delirium in Critically Ill Patients.
AB - OBJECTIVE: Corticosteroids are frequently used in critically ill patients. We
investigated whether systemic corticosteroid use increases the probability of
transitioning to delirium in a large population of mixed medical-surgical ICU
patients. DESIGN: Prospective cohort study. SETTING: A 32-bed medical-surgical
ICU at an academic medical center. PATIENTS: Critically ill adults (n = 1,112),
admitted to the ICU for more than 24 hours without a condition that could hamper
delirium assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Systemic
corticosteroid exposure was measured daily and converted to prednisone
equivalents (milligrams). Daily mental status was classified as coma, delirium,
or an awake without delirium state. Transitions between states were analyzed
using a first-order Markov multinomial logistic regression model with 11
different covariables, with the transition from an awake without delirium state
to delirium as a primary interest. Among the 1,112 patients, corticosteroids were
administered on 35% (3,483/9,867) of the ICU days at a median dose of 50 mg
(interquartile range, 25-75 mg) prednisone equivalent. Administration of a
corticosteroid, and any increase in the dose of the corticosteroid given on
exposure days, was not significantly associated with the transition to delirium
(adjusted odds ratio, 1.08; 95% CI, 0.89-1.32 and adjusted odds ratio, 1.00; 95%
CI, 0.99-1.01, per 10 mg increase in prednisone equivalent). CONCLUSIONS: In a
large population of mixed medical-surgical ICU patients, systemic corticosteroid
use was not associated with an increased probability of transitioning to
delirium.
PMID- 26427590
TI - Long-Term beta-Blocker Therapy Decreases Blood Lactate Concentration in Severely
Septic Patients.
AB - OBJECTIVES: Measurement of blood lactate concentration in the early management of
sepsis is an important step in severity assessment. High blood lactate levels in
the early phase of sepsis have classically been thought to be related to tissue
hypoxia, but other factors could intervene. We hypothesized that the activation
of glycolysis through beta-adrenergic stimulation by endogenous catecholamines
plays an important role in lactate production and that long-term beta-blocker
therapy could affect the lactate concentration in patients with severe sepsis and
septic shock. DESIGN: Retrospective cohort study. SETTING: Emergency department.
PATIENTS: Two hundred sixty patients with severe sepsis or septic shock were
included. Twenty-five percent were previously treated with beta-blockers.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recorded initial vital
signs, the source of infection, mortality at 28 days, blood lactate
concentration, and Predisposition Insult Response of Organ failure and Sequential
Organ Failure Assessment scores using an electronic database. Blood lactate
concentration was significantly lower in patients previously treated with beta
blockers (3.9 +/- 2.3 mmol/L vs 5.6 +/- 3.6 mmol/L; p < 0.001). This difference
was still significant after controlling for mortality (p < 0.005), for the level
of the Predisposition Insult Response of Organ failure (p < 0.05) and Sequential
Organ Failure Assessment (p < 0.05) scores, and for the source of infection (p <
0.05). Nearly four times more patients treated with beta-blockers had normal
blood lactate levels (p< 0.001). Only two factors were significantly and
independently associated with normal blood lactate concentration during severe
sepsis and septic shock: survival (p = 0.03) and beta-blocker therapy (p = 0.01).
CONCLUSIONS: Long-term beta-blocker therapy decreases blood lactate concentration
of severely ill septic patients at presentation. We conclude that the use of
blood lactate measurement as a triage tool in the initial assessment of septic
patients with beta-blocker therapy may underestimate the severity of the sepsis.
PMID- 26427592
TI - Nutritional Status and Mortality in the Critically Ill.
AB - OBJECTIVES: The association between nutritional status and mortality in
critically ill patients is unclear based on the current literature. To clarify
this relation, we analyzed the association between nutrition and mortality in a
large population of critically ill patients and hypothesized that mortality would
be impacted by nutritional status. DESIGN: Retrospective observational study.
SETTING: Single academic medical center. PATIENTS: Six thousand five hundred
eighteen adults treated in medical and surgical ICUs between 2004 and 2011.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All cohort patients received
a formal, in-person, standardized evaluation by a registered dietitian. The
exposure of interest, malnutrition, was categorized as nonspecific malnutrition,
protein-energy malnutrition, or well nourished and determined by data related to
anthropometric measurements, biochemical indicators, clinical signs of
malnutrition, malnutrition risk factors, and metabolic stress. The primary
outcome was all-cause 30-day mortality determined by the Social Security Death
Master File. Associations between nutrition groups and mortality were estimated
by bivariable and multivariable logistic regression models. Adjusted odds ratios
were estimated with inclusion of covariate terms thought to plausibly interact
with both nutrition status and mortality. We used propensity score matching on
baseline characteristics to reduce residual confounding of the nutrition status
category assignment. In the cohort, nonspecific malnutrition was present in 56%,
protein-energy malnutrition was present in 12%, and 32% were well nourished. The
30-day and 90-day mortality rates for the cohort were 19.1% and 26.6%,
respectively. Nutritional status is a significant predictor of 30-day mortality
following adjustment for age, gender, race, medical versus surgical patient type,
Deyo-Charlson index, acute organ failure, vasopressor use, and sepsis:
nonspecific malnutrition 30-day mortality odds ratio, 1.17 (95% CI, 1.01-1.37);
protein-energy malnutrition 30-day mortality odds ratio, 2.10 (95% CI, 1.70
2.59), all relative to patients without malnutrition. In the matched cohort, the
adjusted odds of 30-day mortality in the group of propensity score-matched
patients with protein-energy malnutrition was two-fold greater than that of
patients without malnutrition. CONCLUSION: In a large population of critically
ill adults, an association exists between nutrition status and mortality.
PMID- 26427593
TI - High Level of Endotoxemia Following Out-of-Hospital Cardiac Arrest Is Associated
With Severity and Duration of Postcardiac Arrest Shock.
AB - OBJECTIVE: To investigate the contribution of endotoxemia to the severity of
postcardiac arrest shock. DESIGN: A prospective monocentric study. SETTING: A
tertiary hospital in Paris, France. PATIENTS: Patients admitted in our ICU after
a successfully resuscitated out-of-hospital cardiac arrest. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Endotoxin measurement was performed in the 12
hours following return of spontaneous circulation using the endotoxin activity
assay. Endotoxin level was classified as low (< 0.4 endotoxin activity),
intermediate (0.4 to < 0.6 endotoxin activity), or high (>= 0.6 endotoxin
activity) according to manufacture guidelines. Severity of shock was assessed by
the vasopressor-free days and by the mean daily dose of vasopressor to insure a
mean arterial pressure of 65-75 mm Hg. Among 92 patients included in the study,
60 presented a postcardiac arrest shock. Endotoxemia level was higher in patients
with postcardiac arrest shock. Among these patients, by multivariate linear
regression, high endotoxin class (adjusted estimate -2.0; 95% CI, -3.90 to
0.11), public place of cardiac arrest (adjusted estimate, 1.47; 95% CI, 0.007 to
2.93), and time to return of spontaneous circulation (adjusted estimate -0.08;
95% CI, -0.13 to -0.03) were independently associated with the number of
vasopressor-free days. Furthermore, high endotoxin class (adjusted estimate,
97.95; 95% CI, 20.5 to 175.4) and a nonshockable rhythm (adjusted estimate, 59.9;
95% CI, 6.2 to 113.7) were the sole factors independently associated with the
mean daily dose of vasopressors. CONCLUSIONS: In patients successfully
resuscitated from cardiac arrest with a postcardiac arrest shock, high level of
endotoxemia is independently associated with duration of postcardiac arrest shock
and the amount of vasopressive drugs. Whether treatment targeting endotoxemia
could be beneficial in the management of postcardiac arrest shock needs to be
studied in further randomized controlled studies.
PMID- 26427595
TI - Special Issue "Proteomics in India": Gazing Forward while Reflecting on the
Lessons Learned in Global Proteomics.
PMID- 26427594
TI - Predictors of Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth
Factor-Binding Protein-3 in Critical Illness.
AB - OBJECTIVE: To characterize predictors of insulin-like growth factor-1 and insulin
like growth factor-binding protein-3 in acute critical illness with the
hypothesis that acute factors associated with critical illness will more strongly
predict circulating insulin-like growth factor-1 and insulin-like growth factor
binding protein-3 than chronic clinical or genetic factors. DESIGN: Observational
study nested within a large prospective study using multivariable linear
regression to model circulating insulin-like growth factor-1 and insulin-like
growth factor-binding protein-3 with acute and chronic clinical variables, and
genotype from five polymorphisms in insulin-like growth factor pathway genes.
SETTING: ICUs from two large academic medical centers. PATIENTS: Five hundred
forty-three Caucasian patients with risk factors for acute respiratory distress
syndrome and available plasma from early in critical illness. INTERVENTIONS:
None. MEASUREMENTS AND MAIN RESULTS: Total insulin-like growth factor-1 and
insulin-like growth factor-binding protein-3 were measured in plasma using
IMMULITE assays (Siemens, Malvern, PA). We examined age, gender, body mass index,
cirrhosis, and diabetes, as well as Acute Physiology, Age, and Chronic Health
Evaluation III score, acute hepatic dysfunction, pneumonia and aspiration,
sepsis/septic shock, acute respiratory distress syndrome, and receipt of
corticosteroids. Body mass index, cirrhosis, and acute respiratory distress
syndrome were strongly associated with insulin-like growth factor-1 and insulin
like growth factor-binding protein-3 levels; Acute Physiology, Age, and Chronic
Health Evaluation III was strongly associated with insulin-like growth factor-1
levels; and age was strongly associated with insulin-like growth factor-binding
protein-3. Five polymorphisms (IGF1: rs1520220, rs35767, rs2946834; IGFBP1:
rs4619; IGFBP3: rs2854746) were analyzed for associations with plasma levels.
When genotypes were added to models, rs2854746 was significantly associated with
plasma insulin-like growth factor-binding protein-3. Genotype explained an
additional 2% of variability with an overall adjusted R-square of 0.18.
CONCLUSIONS: Despite the acute derangements of critical illness, both acute and
chronic health factors significantly influence circulating levels of insulin-like
growth factor-1 and insulin-like growth factor-binding protein-3 early in
critical illness. rs2854746 is also significantly associated with insulin-like
growth factor-binding protein-3 levels in this ICU cohort. Overall, phenotypic
and genotypic factors explained only a modest amount of variability in insulin
like growth factor-1 and insulin-like growth factor-binding protein-3. Further
research is needed to understand how to apply these findings to patient care.
PMID- 26427596
TI - The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration,
reinstatement of cocaine-seeking and cocaine induced locomotor activity.
AB - Lorcaserin (Lorqess, Belviq((r))) is a selective 5-HT(2C) receptor agonist that
has received FDA approval for the treatment of obesity. 5-HT(2C) receptor
agonists are also efficacious in decreasing multiple aspects of cocaine
motivation and reward in preclinical models. This would suggest that lorcaserin
is a clinically available therapeutic with the potential to treat cocaine
addiction. Here we report the effects of lorcaserin (0.1 mg/kg-1.0 mg/kg) on
multiple aspects of cocaine-related behaviours in rats. We find that lorcaserin
dose-dependently decreases cocaine self-administration on progressive and fixed
ratio schedules of reinforcement. Lorcaserin also reduces reinstatement of
cocaine-seeking behaviour in response to priming injections of cocaine and/or
reintroduction of cocaine-associated cues. Finally, lorcaserin dose-dependently
decreases cocaine-induced hyperlocomotion. Our results, when considered in
concert with similar emergent findings in non-human primates, strongly support
continued research into the potential of lorcaserin as a clinical treatment for
cocaine addiction.
PMID- 26427598
TI - Helical computed tomography scanning of the larynx and upper trachea in rabbits.
AB - BACKGROUND: Computed tomography (CT) is used to evaluate the human
tracheobronchial tree because of its unsurpassed ability to visualize the airway
and surrounding structures. To establish an ideal animal model for studying
subglottic stenosis, we assessed the size and morphology of the normal rabbit's
laryngotracheal airway by helical CT. We measured luminal dimensions at the
levels of the arytenoid and cricoid cartilages and the first, third, and eighth
tracheal rings. At all levels, the axial slices were used to calculate the
maximum anteroposterior (AP) dimension, transverse dimension, and cross-sectional
areas. We measured the tracheal length from the cricoid to the third and eighth
tracheal rings on sagittal reformation. We assessed the hyoid, thyroid, cricoid,
arytenoid, and tracheal rings for the presence of calcific or soft tissue
densities. We also addressed the presence or absence of pre-epiglottic and
paraglottic fat. RESULTS: The mean AP tracheal dimension +/- standard deviation
(SD) was 8.6 +/- 0.5 mm at the arytenoid level, 8.2 +/- 0.7 mm at the cricoid
level, and 7.7 +/- 0.2 mm at the first tracheal ring level. The transverse
tracheal dimension +/-SD was 5.3 +/- 0.1 mm at the arytenoid level, 5.5 +/- 0.5
mm at the cricoid level, and 6.1 +/- 0.6 mm at the first tracheal ring level. The
mean tracheal area +/-SD was 35.7 +/- 2.2 mm(2) at the arytenoid level, 35.8 +/-
5.1 mm(2) at the cricoid level, and 39.2 +/- 4.3 mm(2) at the first tracheal ring
level. The tracheal length +/-SD was 10.7 +/- 2.3 mm from the cricoid to the
third tracheal ring and 19.1 +/- 1.14 mm to the eighth tracheal ring. There was
complete calcification of the hyoid in all rabbits. Only two rabbits showed
complete thyroid, arytenoid, or tracheal ring calcification. The remaining airway
components were otherwise either uncalcified or partially calcified. The uvula,
epiglottis, aryepiglottic fold, vallecula, piriform sinus, true/false vocal
cords, and pre-epiglottic/paraglottic fat were not seen in any rabbit.
CONCLUSIONS: Helical CT investigation provides good, highly definitive anatomic
details of the larynx and trachea in rabbits. Such results may be used in further
evaluation of the normal airway and in cases of subglottic stenosis.
PMID- 26427597
TI - Deubiquitinating enzyme USP37 regulating oncogenic function of 14-3-3gamma.
AB - 14-3-3 is a family of highly conserved protein that is involved in a number of
cellular processes. In this study, we identified that the high expression of 14-3
3gamma in various cancer cell lines correlates with the invasiveness of the
cancer cells. Overexpression of 14-3-3gamma causes changes to the morphologic
characteristics of cell transformation, and promotes cell migration and invasion.
The cells overexpressed with 14-3-3gamma have been shown to stimulate foci and
tumor formation in SCID-NOD mice in concert with signaling components as reported
with the 14-3-3beta. In our previous study, we demonstrated that 14-3-3gamma
inhibits apoptotic cell death and mediates the promotion of cell proliferation in
immune cell lines. Earlier, binding partners for 14-3-3gamma were defined by
screening. We found that USP37, one of deubiquitinating enzymes (DUBs), belongs
to this binding partner group. Therefore, we investigated whether 14-3-3gamma
mediates proliferation in cancer cells, and 14-3-3gamma by USP37 is responsible
for promoting cell proliferation. Importantly, we found that USP37 regulates the
stability of ubiquitin-conjugated 14-3-3gamma through its catalytic activity.
This result implies that the interactive behavior between USP37 and 14-3-3gamma
could be involved in the regulation of 14-3-3gamma degradation. When all these
findings are considered together, USP37 is shown to be a specific DUB that
prevents 14-3-3gamma degradation, which may contribute to malignant
transformation via MAPK signaling pathway, possibly providing a new target for
therapeutic objectives of cancer.
PMID- 26427599
TI - Contributions of voluntary activation deficits to hand weakness after stroke.
AB - BACKGROUND: Hemiparetic stroke survivors often exhibit profound weakness in the
digits of the paretic hand, but the relative contribution of potential
biomechanical and neurological impairment mechanisms is not known. Establishing
sources of impairment would help in guiding treatment. OBJECTIVE: The present
study sought to quantify the role of diminished capacity to voluntarily active
finger flexor and extensor muscles as one possible neurological mechanism.
METHODS: Two groups of stroke survivors with "severe" (N = 9) or "moderate" (N =
9) hand impairment and one group of neurologically intact individuals (N = 9)
participated. Subjects were asked to create isometric flexion force and extension
force, respectively, with the tip of the middle finger. The maximum voluntary
force (MVF) and the maximum stimulated force (MSF) produced by an applied train
of electrical current pulses (MSF) were recorded for flexion and extension.
Percent voluntary activation (PVA) was computed from MVF and MSF. RESULTS:
Significant deficits in both MVF and PVA were observed for stroke subjects
compared to control subjects. For example, activation deficits were >80% for
extensor digitorum communis (EDC) for the "severe" group. Maximum voluntary force
and PVA deficits were greater for EDC than for flexor digitorum superficialis
(FDS) for stroke subjects with severe impairment. Maximum voluntary force and PVA
correlated significantly for stroke subjects but not for control subjects.
CONCLUSIONS: Although extrinsic finger muscles could be successfully recruited
electrically, voluntary excitation of these muscles was substantially limited in
stroke survivors. Thus, finger weakness after stroke results predominantly from
the inability to fully activate the muscle voluntarily.
PMID- 26427600
TI - Tremelimumab-associated tumor regression following after initial progression: two
case reports.
AB - The human IgG2 monoclonal antibody tremelimumab is an immune checkpoint inhibitor
that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). The therapeutic
response of anti-CTLA-4 monoclonal antibodies possess unique kinetics, in that
antitumor responses are often observed after initial short-term disease
progression, in some cases as long as 6-12 months after anti-CTLA-4 treatment
initiation. Here, we report two cases: one of bile duct cancer and the other of
squamous cell carcinoma of unknown primary, both of which demonstrated initial
rapid disease progression followed by dramatic tumor shrinkage after one or two
doses of tremelimumab, without any immune-related adverse events. This delayed,
yet dramatic antitumor response suggests that tremelimumab may hold promise in
the treatment of solid tumors.
PMID- 26427601
TI - Asthma symptoms in obese adults: The challenge of achieving asthma control.
AB - The association between asthma and obesity is well-described, but not
straightforward, and according to current guidelines asthma control is more
difficult to achieve in obese patients. The currently available studies
evaluating response to pharmacological asthma therapy in obese patients show that
these patients have an altered, in general less favorable, response to both
reliever and controller medication compared to normal weight patients. However,
at present, the limited available evidence precludes evidence-based
recommendations. The 'obesity-related asthma' phenotype has different
characteristics, including association with atopy and type of airway
inflammation, compared to 'classic' asthma. Furthermore, weight loss in patients
with this phenotype leads to an improvement in symptoms, lung function, and
airway responsiveness, as well as a reduction in medication utilization and
hospital admissions. Obese patients, who present with symptoms suggesting a
diagnosis of asthma, may have a distinct phenotype or a disease mimicking asthma,
likely to have a potentially higher remission rate. And by that, our approach to
this group of patients should combine pharmacologic and non-pharmacologic
therapies, including exercise, weight loss and dietary interventions, instead of
primarily focusing on disease control by stepping up asthma therapy.
PMID- 26427602
TI - Risk of adverse pregnancy outcomes stratified for pre-pregnancy body mass index.
AB - OBJECTIVE: To estimate the risk of adverse maternal and perinatal outcomes in
women with different pre-pregnancy body mass index (BMI). METHODS: We conducted a
cohort study with 14 451 singleton pregnancies in 15 medical centers in Beijing
between 20 June 2013 and 30 November 2013 using cluster random sampling. We
divided participants into four groups based on pre-pregnancy BMI: Group A
(underweight): BMI < 18.5 kg/m(2), Group B (normal): 18.5-23.9 kg/m(2), Group C
(overweight): 24-27.9 kg/m(2), Group D (obesity): >=28 kg/m(2). We used
multivariate analysis to evaluate the association of the risk of adverse
pregnancy outcomes and pre-pregnancy BMI. RESULTS: The prevalence of maternal
overweight and obesity was 14.82% (2142/14 451) and 4.71% (680/14 451) in the
study population, respectively. Higher pre-pregnancy BMI is associated with
higher prevalence of gestational diabetes (GDM), macrosomia, Cesarean section (C
section), preeclampsia and postpartum hemorrhage. Pre-pregnancy overweight or
obesity increases the risk of adverse pregnancy outcomes, regardless of GDM
status. CONCLUSIONS: Pre-pregnancy overweight or obesity is associated with
increased risk of adverse pregnancy outcomes. Nutrition counseling is recommended
before pregnancy in women who have overweight or obesity.
PMID- 26427603
TI - The Sojourn from Parenteral to Oral Taxanes using Nanocarrier Systems: A Patent
Review.
AB - Natural diterpenoid taxanes and their semisynthetic analogues have already made
an indelible mark in the chemotherapeutic world for treating various kinds of
malignancies. However, due to the absence of any functional groups which could be
ionized by pH alteration or which may participate in salt formation, these
taxanes, exhibit low solubility. Parenteral administration of taxanes with
solubilising agents such as Cremophor EL and Polysorbate 80 results in
undesirable side effects like hypersensitivity reactions, myelosuppression and
peripheral neuropathy. Nanoengineered drug delivery systems like nanoemulsions,
nanocrystals, dendrimers, micelles, selfnanoemulsifying systems, liposomes, solid
lipid nanoparticles and biodegradable polymeric nanoparticles, in this regard,
tend to surmount these ostensible challenges, when administered orally. The bare
taxanes encounter several inadequacies, namely poor aqueous solubility,
structural instability in physiological fluids, p-glycoprotein recognition,
hepatic first-pass effect, gastrointestinal permeability, and Cytochrome P450
enzymatic metabolism, etc. In addition, nanoscaled oral delivery improves drug
encapsulation, thus facilitating diffusion through intestinal epithelium,
modification of pharmacokinetic and tissue distribution profile of the drug,
eventually resulting in flexibility of dosing schedules, prevention of discomfort
of the injection and hospitalization, and improved patient convenience. The
current review paper endeavors to provide a bird's eye view on the significant
headway made on orally-administered nanosystems of taxanes and their analogues
through patent applications published till date since its discovery.
PMID- 26427604
TI - Promoting social capital to alleviate loneliness and improve health among older
people in Spain.
AB - Loneliness is especially frequent among older people in Southern Europe.
Furthermore, promoting social capital to tackle loneliness and its health effects
is an understudied intervention strategy. Therefore, a complex intervention was
piloted in Spain in a pre-post study with a 2-year follow-up. Its aims were to
explore the feasibility of the intervention and its short- and long-term effects.
It was conducted in one mixed rural-urban and two urban areas of diverse
socioeconomic levels from 2011 to 2012. The intervention framework was based on
social capital theory applying a behaviour change model and care co-ordination.
The intervention comprised: (i) a co-ordinated action aimed at building a network
between primary healthcare centres and community assets in the neighbourhood and
(ii) a group-based programme, which promoted social capital among lonely older
people, especially social support and participation. Older people active in
senior centres volunteered as gatekeepers. The main outcome domain was
loneliness. Secondary outcome domains were participation, social support, self
perceived health, quality of life, depressive symptoms and use of health
resources. Pre-post changes were assessed with t-test, Wilcoxon signed-rank test
and McNemar's test. Differences between the three time points were assessed with
a one-way ANOVA with repeated measures. Social workers and nurses were
successfully involved as group leaders, 10 volunteers took part and 38
participants were included. After the intervention, loneliness decreased while
social participation and support significantly increased. Furthermore, the number
of visits to nurses increased. Exactly 65.8% of the participants built social
contacts within the group and 47.4% became engaged in new activities. Two years
later, social effects were maintained and depressive symptoms had decreased.
Exactly 44.7% of the participants continued to be in contact with at least one
person from the group and 39.5% continued participating. The intervention
contributes a novel and feasible social capital-based approach for alleviating
loneliness among older adults while prompting meaningful changes in their lives.
PMID- 26427605
TI - Genetic traceability of cattle using an OpenArray genotyping platform.
PMID- 26427606
TI - SCN4A pore mutation pathogenetically contributes to autosomal dominant essential
tremor and may increase susceptibility to epilepsy.
AB - Essential tremor (ET) is the most prevalent movement disorder, affecting millions
of people in the USA. Although a positive family history is one of the most
important risk factors for ET, the genetic causes of ET remain unknown. In an
attempt to identify genetic causes for ET, we performed whole-exome sequencing
analyses in a large Spanish family with ET, in which two patients also developed
epilepsy. To further assess pathogenicity, site-directed mutagenesis, mouse and
human brain expression analyses, and patch clamp techniques were performed. A
disease-segregating mutation (p.Gly1537Ser) in the SCN4A gene was identified.
Posterior functional analyses demonstrated that more rapid kinetics at near
threshold potentials altered ion selectivity and facilitated the conductance of
both potassium and ammonium ions, which could contribute to tremor and increase
susceptibility to epilepsy, respectively. In this report, for the first time, we
associated the genetic variability of SCN4A with the development of essential
tremor, which adds ET to the growing list of neurological channelopathies.
PMID- 26427591
TI - Being Overweight Is Associated With Greater Survival in ICU Patients: Results
From the Intensive Care Over Nations Audit.
AB - OBJECTIVE: To assess the effect of body mass index on ICU outcome and on the
development of ICU-acquired infection. DESIGN: A substudy of the Intensive Care
Over Nations audit. SETTING: Seven hundred thirty ICUs in 84 countries. PATIENTS:
All adult ICU patients admitted between May 8 and 18, 2012, except those admitted
for less than 24 hours for routine postoperative monitoring (n = 10,069). In this
subanalysis, only patients with complete data on height and weight (measured or
estimated) on ICU admission in order to calculate the body mass index were
included (n = 8,829). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
Underweight was defined as body mass index less than 18.5 kg/m, normal weight as
body mass index 18.5-24.9 kg/m, overweight as body mass index 25-29.9 kg/m, obese
as body mass index 30-39.9 kg/m, and morbidly obese as body mass index greater
than or equal to 40 kg/m. The mean body mass index was 26.4 +/- 6.5 kg/m. The ICU
length of stay was similar among categories, but overweight and obese patients
had longer hospital lengths of stay than patients with normal body mass index (10
[interquartile range, 5-21] and 11 [5-21] vs 9 [4-19] d; p < 0.01 pairwise). ICU
mortality was lower in morbidly obese than in normal body mass index patients
(11.2% vs 16.6%; p = 0.015). In-hospital mortality was lower in morbidly obese
and overweight patients and higher in underweight patients than in those with
normal body mass index. In a multilevel Cox proportional hazard analysis,
underweight was independently associated with a higher hazard of 60-day in
hospital death (hazard ratio, 1.32; 95% CI, 1.05-1.65; p = 0.018), whereas
overweight was associated with a lower hazard (hazard ratio, 0.79; 95% CI, 0.71
0.89; p < 0.001). No body mass index category was associated with an increased
hazard of ICU-acquired infection. CONCLUSIONS: In this large cohort of critically
ill patients, underweight was independently associated with a higher hazard of 60
day in-hospital death and overweight with a lower hazard. None of the body mass
index categories as independently associated with an increased hazard of
infection during the ICU stay.
PMID- 26427607
TI - Impaired bone remodeling and its correction by combination therapy in a mouse
model of mucopolysaccharidosis-I.
AB - Mucopolysaccharidosis-I (MPS-I) is a lysosomal storage disease (LSD) caused by
inactivating mutations of IDUA, encoding the glycosaminoglycan-degrading enzyme
alpha-l-iduronidase. Although MPS-I is associated with skeletal abnormalities,
the impact of IDUA deficiency on bone remodeling is poorly defined. Here we
report that Idua-deficient mice progressively develop a high bone mass phenotype
with pathological lysosomal storage in cells of the osteoblast lineage.
Histomorphometric quantification identified shortening of bone-forming units and
reduced osteoclast numbers per bone surface. This phenotype was not transferable
into wild-type mice by bone marrow transplantation (BMT). In contrast, the high
bone mass phenotype of Idua-deficient mice was prevented by BMT from wild-type
donors. At the cellular level, BMT did not only normalize defects of Idua
deficient osteoblasts and osteocytes but additionally caused increased
osteoclastogenesis. Based on clinical observations in an individual with MPS-I,
previously subjected to BMT and enzyme replacement therapy (ERT), we treated Idua
deficient mice accordingly and found that combining both treatments normalized
all histomorphometric parameters of bone remodeling. Our results demonstrate that
BMT and ERT profoundly affect skeletal remodeling of Idua-deficient mice, thereby
suggesting that individuals with MPS-I should be monitored for their bone
remodeling status, before and after treatment, to avoid long-term skeletal
complications.
PMID- 26427608
TI - Design, Synthesis and in vitro Evaluation of Indolotacrine Analogues as
Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease.
AB - Novel indolotacrine analogues were designed, synthesized, and evaluated as
potential drugs for the treatment of Alzheimer's disease. By using a multitarget
directed ligand approach, compounds were designed to act simultaneously as
cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors. The compounds were
also evaluated for antioxidant, cytotoxic, hepatotoxic, and blood-brain barrier
(BBB) permeability properties. Indolotacrine 9 b (9-methoxy-2,3,4,6-tetrahydro-1H
indolo[2,3-b]quinolin-11-amine) showed the most promising results in the in vitro
assessment; it is a potent inhibitor of acetylcholinesterase (AChE IC50 : 1.5
MUm), butyrylcholinesterase (BChE IC50 : 2.4 MUm) and MAO A (IC50 : 0.49 MUm),
and it is also a weak inhibitor of MAO B (IC50 : 53.9 MUm). Although its
cytotoxic (IC50 : 5.5+/-0.4 MUm) and hepatotoxic (IC50 : 1.22+/-0.11 MUm)
profiles are not as good as those of the standard 7-methoxytacrine (IC50 : 63+/-4
and 11.50+/-0.77 MUm, respectively), the overall improvement in the inhibitory
activities and potential to cross the BBB make indolotacrine 9 b a promising lead
compound for further development and investigation.
PMID- 26427609
TI - Increased levels of MIP-1alpha in CSF and serum of ALS.
AB - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive
neurodegenerative disease with complicated pathogenesis. No effective diagnostic
test and cure exists for the disease at present. We detected the levels of MIP
1alpha in cerebrospinal fluid (CSF) and serum and then further evaluated whether
MIP-1alpha levels correlate with the severity and progression of ALS. METHODS: We
used ELISAs to detect MIP-1alpha levels from 58 patients with ALS and 45 age- and
gender-matched controls. The patients with ALS were also clinically evaluated
with the revised ALS functional rating scale (ALSFRS-r). Moreover, we followed up
with 40 cases of ALS by way of call or clinic visit 4 years after enrollment in
this study. Finally, we assessed the correlations between MIP-1alpha levels and
various clinical parameters. RESULTS: We found that the levels of MIP-1alpha in
patients with ALS significantly increased compared to controls and they were
positively correlated with duration. MIP-1alpha showed negative correlations with
disease progression rate and the decrease in ALSFRS-r. Furthermore, the
cumulative survival of patients with ALS with high levels of MIP-1alpha exceeded
patients with low MIP-1alpha levels. CONCLUSIONS: MIP-1alpha levels increased in
both CSF and serum of patients with ALS, and it may be a potential
neuroprotective biomarker in ALS.
PMID- 26427610
TI - Joint attention behaviours in people with profound intellectual and multiple
disabilities: the influence of the context.
AB - BACKGROUND: In spite of the profound cognitive and physical problems, people with
profound intellectual and multiple disabilities (PIMD) are able to develop joint
attention behaviours (JAB) and benefit from positive interactions. AIMS: To
investigate which context factors influence the JAB of people with PIMD. METHOD:
Based on video recordings of 45 participants, JAB and context factors were
analysed. RESULTS: An unstructured interaction situation produced the most
responses of a person with PIMD, whereas a structured interaction situation
produced the most initiatives. Furthermore, the familiarity of the partner and
the familiarity of objects used in the interaction had no influence on the JAB.
The sensitivity of the interaction partner was positively related to the presence
of JAB. CONCLUSIONS: Interaction partners of people with PIMD should be aware of
both the ability of people with PIMD to use JAB and the influence of different
context factors on these JAB.
PMID- 26427611
TI - Anti-HIV-1 integrase effect of compounds from Aglaia andamanica leaves and
molecular docking study with acute toxicity test in mice.
AB - CONTEXT: Acquired immunodeficiency syndrome (AIDS) is a serious health problem
worldwide. It has been reported that Aglaia andamanica Hiern (Meliaceae) leaves
possessed an antiviral effect. Therefore, a search of anti-HIV-1 integrase (HIV-1
IN) agents from A. andamanica is a promising target. OBJECTIVE: The objective of
this study is to evaluate anti-HIV-1 IN activity of isolated compounds from A.
andamanica using an in vitro assay and molecular docking study as well as testing
acute toxicity in mice using the up and down method. MATERIALS AND METHODS: The
leaves and compounds (3-100 MUg/mL) from A. andamanica were determined for the
anti-HIV-1 IN effect using the multiplate integration assay (MIA) by detection
the absorbance of the final product, p-nitrophenol, at 405 nm. The molecular
docking with the HIV-1 IN of the active compound N-methyl-trans-4-hydroxy-l
proline (10) was also studied. The Swiss albino mice were used for an acute
toxicity test. RESULTS AND DISCUSSION: Among the isolated compounds, 10 showed
marked anti-HIV-1 IN effect with an IC50 value of 11.8 MUg/mL, whereas other
compounds were inactive (IC50 value > 100 MUg/mL). The molecular docking of
compound 10 with an HIV-1 IN enzyme was also studied. The result revealed that
this compound formed the hydrogen bonding with the Thr66, Asn155, and Lys159 of
the HIV-1 IN binding site. The acute toxicity of the A. andamanica extract was
not observed at the dose 2000 mg/kg mice. This is the first report of A.
andamanica for anti-HIV-1 IN activity.
PMID- 26427612
TI - Stereodivergent Dual Catalytic alpha-Allylation of Protected alpha-Amino- and
alpha-Hydroxyacetaldehydes.
AB - Fully stereodivergent dual-catalytic alpha-allylation of protected alpha-amino-
and alpha-hydroxyacetaldehydes is achieved through iridium- and amine-catalyzed
substitution of racemic allylic alcohols with chiral enamines generated in situ.
The operationally simple method furnishes useful aldehyde building blocks in good
yields, more than 99% ee, and with d.r. values greater than 20:1 in some cases.
Additionally, the gamma,delta-unsaturated products can be further functionalized
in a stereodivergent fashion with high selectivity and with preservation of
stereochemical integrity at the Calpha position.
PMID- 26427613
TI - Type of LDLR mutation and the pharmacogenetics of familial hypercholesterolemia
treatment.
AB - Familial hypercholesterolemia (FH) is an autosomal dominant disease mainly caused
by mutations in the low-density lipoprotein receptor (LDLR) gene. FH patients
present a wide variability regarding response to drugs and they are usually
undertreated. Here, we review studies that evaluated the association between the
type of LDLR mutation and the response to lipid-lowering therapy. The main
findings were that patients with a null LDLR mutation had: higher baseline LDL-C,
higher LDL-C after drug therapy, lower proportion of patients within the LDL-C
target value and higher frequencies of CVD. Thus, we conclude that FH patients
harboring a null mutation have a trend to an increased risk, even if diagnosis is
early established and lipid-lowering treatment instituted. It is suggested that
these individuals may benefit from the use of newly approved lipid-lowering
agents.
PMID- 26427614
TI - Creation of the first ultra-low gluten barley (Hordeum vulgare L.) for coeliac
and gluten-intolerant populations.
AB - Coeliac disease is a well-defined condition that is estimated to affect
approximately 1% of the population worldwide. Noncoeliac gluten sensitivity is a
condition that is less well defined, but is estimated to affect up to 10% of the
population, and is often self-diagnosed. At present, the only remedy for both
conditions is a lifelong gluten-free diet. A gluten-free diet is often expensive,
high in fat and low in fibre, which in themselves can lead to adverse health
outcomes. Thus, there is an opportunity to use novel plant breeding strategies to
develop alternative gluten-free grains. In this work, we describe the breeding
and characterization of a novel ultra-low gluten (ULG) barley variety in which
the hordein (gluten) content was reduced to below 5 ppm. This was achieved using
traditional breeding strategies to combine three recessive alleles, which act
independently of each other to lower the hordein content in the parental
varieties. The grain of the initial variety was shrunken compared to wild-type
barleys. We implemented a breeding strategy to improve the grain size to near
wild-type levels and demonstrated that the grains can be malted and brewed
successfully. The ULG barley has the potential to provide novel healthy foods and
beverages for those who require a gluten-free diet.
PMID- 26427615
TI - Mesoporous Zirconium Phenylenesiliconate-phosphonate Hybrids with Ordered
Lamellar Nanostructures.
AB - Novel ordered lamellar mesostructure pZrPS-2 was hydrothermally prepared by using
zirconium propoxide and 4-(EtO)2OPC6H4Si(OEt)3 (pPPS-E), which was hydrolyzed to
organic building units substituted with both siliconate and phosphonate groups,
in the presence of Cn TAB and TMAOH. The pZrPS-2 materials were obtained at a
Zr/PPS ratio of 2 or higher and the basal spacing was increased by using a longer
chain surfactant (n = 12-18). Removal of the occluded surfactants at 300 degrees
C resulted in retention of the lamellar structure with negligible shrinkage of
the interlayer distance. Nitrogen adsorption studies revealed the ordered
mesoporous nature of pZrPS-2 with a pore diameter of approximately 2 to 3 nm. The
lamellar structure is assumed to be composed of layers that include zirconia
based crystalline nanodomains and interlayer pillars mainly based on PPS units.
Although lamellar structures with the same crystalline phase also formed when no
surfactant was added or when the meta isomer of PPS was used, no mesoporous
materials were obtained except pZrPS-2. A possible schematic model to elucidate
these results is also proposed.
PMID- 26427617
TI - Consider obstructive sleep apnea in patients with oropharyngeal vascular
malformations.
AB - INTRODUCTION: Patients with oropharyngeal vascular malformations with complaints
of upper airway obstruction were referred to a sleep specialist to investigate
the existence of obstructive sleep apnea (OSA). METHODS: Demography, complaints,
localization, and extent of the malformation were noted. The Epworth Sleeping
Scale (ESS) and a polysomnography were performed to analyze the existence of OSA.
RESULTS: Thirteen patients with vascular malformations in the upper oropharyngeal
tract were referred, with a mean age of 49 years (range, 20-77 years). The male:
female ratio was 7:6. In 2 patients the ESS was missed, and in the other 11
patients the mean ESS was 11.7 (range, 4-23). After polysomnography, 11 of the 13
patients (85%) were diagnosed with OSA, of whom 7 patients had severe OSA.
CONCLUSION: Patients with oropharyngeal vascular malformations with complaints of
upper airway obstruction have a high risk of OSA, and should be referred to a
sleep specialist.
PMID- 26427616
TI - Incidence of pain flare following palliative radiotherapy for symptomatic bone
metastases: multicenter prospective observational study.
AB - BACKGROUND: Palliative radiotherapy (RT) is an effective treatment for
symptomatic bone metastases. Pain flare, a transient worsening of the bone pain
after RT, has been described in previous reports with different incidence rates.
The aim of the study was to prospectively evaluate the incidence of pain flare
following RT for painful bone metastases and evaluate its effects on pain control
and functionality of the patients. METHODS: Between June 2010 and June 2014, 204
patients were enrolled in this study and 135 patients with complete data were
evaluable. Pain flare was defined as a 2- point increase in worst pain score as
compared with baseline with no decrease in analgesic intake or a 25% increase in
analgesic intake as compared with baseline with no decrease in worst pain score.
All pain medications and worst pain scores were collected before, daily during,
and for 10 days after RT. The Brief Pain Inventory (BPI) was filled out on the
pretreatment and at the 4 weeks follow-up visit. RESULTS: There were 90 men
(66.7%) and 45 women (33.3%). Mean age was 66 years (SD 9.8). The most common
primary cancer site was lung in 42 patients (31.1%), followed by prostate in 27
patients (20.0%). Forty-two patients (31.1%) patients received a single fraction
of 8 Gy and 83 (61.5%) received 20 Gy in five fractions. The overall pain flare
incidence across all centers was 51/135 (37.7%). The majority of pain flares
occurred on days 1-5 (88.2%). The mean duration of the pain flare was 3 days (SD:
3). There were no significant relationships between the occurrence of pain flare
and collected variables. All BPI items measured four weeks after end of RT showed
significant improvement as compared with pretreatment scores (p < 0.001). No
significant differences in BPI time trends were found between patients with and
without flare pain. CONCLUSION: Pain flare is a common event, occurring in nearly
40% of the patients that receive palliative RT for symptomatic bone metastases.
This phenomenon is not a predictor for pain response.
PMID- 26427618
TI - Does a large dehiscent implant surface at placement affect the 5-year treatment
outcome? An assessment of implants placed to support a maxillary overdenture.
AB - The aim of this study was to assess the 5-year clinical and radiographic outcome
of implants with a dehiscent surface at implant placement. A total of 26
consecutive patients (mean age 61.6 years; SD 8.0 years) with at least one
implant with a dehiscent implant surface of >= two thirds of the implant length
on the labial side were included. All implants were placed to support a maxillary
overdenture. The implants were placed with adequate primary stability and the
dehiscent surface was covered with autologous bone, inorganic bovine bone and a
resorbable membrane. Outcome measures were soft tissue conditions, change of
radiographic marginal bone level and implant survival. Baseline data (at loading,
T0) were compared with 1-year (T1) and 5-year (T5) post loading data. Of the 116
implants, 40 implants had no dehiscence, 16 had a buccal dehiscence < two thirds
of the implant length, and 60 implants had a dehiscence >= two thirds. The peri
implant tissues were healthy and 5-year marginal bone changes were well within
normal limits (-0.4 mm; range: -0.8 to -0.1). One implant was lost during the
osseointegration period. Even when implants are placed with a dehiscence >= two
thirds of the buccal implant surface, favorable 5-year peri-implant health can be
achieved provided these dehiscences are covered with autologous bone, inorganic
bone and a resorbable membrane, and there is good initial stability of the
implants.
PMID- 26427619
TI - Outcomes of microvascular free flap reconstruction for mandibular
osteoradionecrosis: A systematic review.
AB - INTRODUCTION: Osteoradionecrosis of the mandible is a devastating complication of
radiotherapy in patients with head and neck cancer. Many cases present at a late
stage, from months to years following completion of radiation therapy. When
medical treatment fails, surgery may be required with a variety of free flaps
available for microvascular reconstructive techniques. OBJECTIVE: To conduct a
systematic review of the literature investigating the outcomes of free flap
reconstruction of the jaw in mandibular osteoradionecrosis and determine the
failure rates of different flap tissue. METHODS: A systematic literature search
was performed using Medline (Ovid) Pubmed and Embase databases and Google
Scholar. Primary outcome measures were flap failures and complications, with
donor site complications representing the secondary outcome measure. Analysis of
pooled outcomes was undertaken for different flaps. RESULTS: 333 articles were
identified and 15 articles met the final inclusion criteria, detailing 368
primary free tissue flap transfers. There was a flap failure rate of 9.8%. There
were 146 post-operative complications (39.7%), the most common being fistula
formation (8.4%), hardware plate exposure (7.1%) and flap wound infections
(6.5%). CONCLUSION: The fibula is the workhorse free flap for reconstruction in
mandibular osteoradionecrosis. Evidence to date is largely limited with the need
for larger powered multi-institutional prospective studies to determine the ideal
flap donor tissue and evaluate patient and treatment predictors of free flap
outcomes in order to tailor the best patient-based surgical approach for
mandibular osteoradionecrosis.
PMID- 26427620
TI - Etiology and injury patterns of maxillofacial fractures from the years 2010 to
2013 in Mecklenburg-Western Pomerania, Germany: A retrospective study of 409
patients.
AB - OBJECTIVE: The aim of the present study was to illustrate the injury patterns and
the etiology of accident victims with maxillofacial fractures in the state of
Mecklenburg-Western Pomerania (M-P), Germany. MATERIAL AND METHODS: Between 2010
and 2013, patients with maxillofacial fractures from the Department of Oral and
Maxillofacial Surgery at the Helios Kliniken Schwerin, were evaluated with a
specially constructed data set in a retrospective analysis. After review of the
patient records, a case-related data collection was performed with the pre-set
characteristics: age, gender, age group, maxillofacial fracture, and cause of
injury. RESULTS: Of 409 patients, 79% (n = 323) were male and 21% (n = 86) were
female. A fracture of the zygomaticomaxillary complex was most frequently
observed (31%; n = 240). Midface fractures with orbital floor involvement were
the most common fracture types (48.4%; n = 137). A significant percentage of the
fractures (45.2%; n = 185) were caused by interpersonal violence; 70.8% (n =
131), and thus the majority of the patients who were treated due to a brutal
offense, had consumed alcohol. Within this group, men in the age group of 20-29
years were most prevalent (38.7%; n = 125). Etiologically, 25.2% (n = 103) of
fractures were caused by a fall. CONCLUSION: The regionalization of data on the
distribution, emergence, and localization of maxillofacial fractures in M-P
allows not only a national comparison but also an international comparison with
areas that are in a similar strong socio-demographic change, as it applies to the
East German population. This provides the opportunity to develop the global
preventive measures and to apply suitable quality management.
PMID- 26427621
TI - Geographic measures of retail food outlets and perceived availability of healthy
foods in neighbourhoods.
AB - OBJECTIVE: To examine associations between geographic measures of retail food
outlets and perceived availability of healthy foods. DESIGN: Cross-sectional.
SETTING: A predominantly rural, eight-county region of South Carolina, USA.
SUBJECTS: Data from 705 household shoppers were analysed using ordinary least
squares regression to examine relationships between geographic measures (presence
and distance) of food outlets obtained via a geographic information system and
perceived availability of healthy foods (fresh fruits and vegetables and low-fat
foods). RESULTS: The presence of a supermarket within an 8.05 km (5-mile) buffer
area was significantly associated with perceived availability of healthy foods
(beta=1.09, P=0.025) when controlling for all other food outlet types. However,
no other derived geographic presence measures were significant predictors of
perceived availability of healthy foods. Distances to the nearest supermarket
(beta=-0.16, P=0.003), dollar and variety store (beta=-0.15, P=0.005) and fast
food restaurant (beta=0.11, P=0.015) were all significantly associated with
perceptions of healthy food availability. CONCLUSIONS: Our results suggest that
distance to food outlets is a significant predictor of healthy food perceptions,
although presence is sensitive to boundary size. Our study contributes to the
understanding and improvement of techniques that characterize individuals' food
options in their community.
PMID- 26427622
TI - An evaluation of a community-based food supplementation for people living with
HIV in Ghana: implications for community-based interventions in Ghana.
AB - BACKGROUND: Community-based care and support services are limited in sub-Saharan
Africa and as a result a high number of people living with HIV (PLHIV) are not
getting the required care and support services. The aim of this study was to
assess the impact of food supplementation services for PLHIV in Ghana on weight
gained and factors associated with weight gained. METHODS: The study employed
mixed methods study design involving quantitative and qualitative techniques.
These were structured questionnaire administered to 200 PLHIV selected through
simple random sampling and a qualitative component consisting of 14 semi
structured interviews with purposefully selected stakeholders and eight focus
group discussions with the beneficiaries. RESULTS: The analysis of the
quantitative data showed on average, beneficiaries had gained weight [mean
difference in weight was 2 kg with 95 % CI (1.1, 2.9), P value <0.001].
Multivariate analysis showed that the support group to which the beneficiary
belonged was the most important determinant of gaining weight. Through the
qualitative interviews, beneficiaries indicated that the anti-retroviral drugs
were making them hungry and the food helped to alleviate that effect.
Notwithstanding, they indicated that the food was nutritious, made them healthy
and strong, contributed to their weight gain and was their main sources of hope
at home when they had no money. CONCLUSIONS: A broad strategy of food
supplementation for PLHIV should be implemented in different ways for different
support groups taking into account the differences between different support
groups when planning such an intervention.
PMID- 26427623
TI - Role of Dectin-1 in the innate immune response of rat corneal epithelial cells to
Aspergillus fumigatus.
AB - BACKGROUND: To observe Dectin-1 expression in fungal keratitis on rat models and
to determine the role of Dectin-1 in innate immune response to Aspergillus
fumigatus. METHODS: Wistar rats were randomly divided into control, fungal
keratitis and pretreatment (pretreated with Laminarin) groups. Samples were used
for conducting immunohistochemical staining and real-time PCR to observe
expression of cytokines like CCL2, CCL3, CXCL1, CXCL2, IL-1beta, TNF-alpha, IL-6,
IL-10. RESULTS: After fungal stimulations, all 7 inflammatory factors, except IL
10, increased with different levels. After 4 h of fungal stimulations, IL-1beta,
IL-6, CCL2, CXCL1 and CXCL2 of pretreatment groups were significantly (p < 0.05)
lower than fungal groups, while the other 3 cytokines had no significant changes.
After 8 h of fungal stimulations, IL-6 and CXCL1 of pretreatment groups were
still significantly (p < 0.05) lower than fungal groups. DISCUSSION: With
progress of fungus stimulation, expression of IL-1beta,CXCL1 ,CXCL2,MCP-1
gradually increased, whilepretreated with Laminarin to block Dectin-1, these
expression decreased, indicating that Dectin-1 maypromote immune reaction through
them. IL-10 decreased in fungal group because of itsimmunosuppressive effect at
4h, and it began to increase at 8h to suppress Th1 inflammation response inorder
to avoid excessive tissue damage. CONCLUSION: Dectin-1 in early period of innate
immune responses in rat fungal keratitis might work through IL-1beta, IL-6, CCL2,
CXCL1, CXCL2 to recruit neutrophils and macrophages to participate anti-fungal
immunity.
PMID- 26427626
TI - Electrochemical lithiation-induced polymorphism of anthraquinone derivatives
observed by operando X-ray diffraction.
AB - The use of organic molecules represents a very attractive and promising
alternative for electrical energy storage applications. Quinones, in general, and
anthraquinones, in particular, are especially attractive due to their ability to
reversibly exchange multiple electrons per formula unit. When used as the active
electrode material in a real lithium-ion battery (LIB), crystalline anthraquinone
powders reversibly change crystal packing as a function of state-of-charge (redox
state), with well-defined voltage plateaus appearing concomitantly with new
phases. Operando powder X-ray diffraction (XRD) is a powerful method for
screening the structural stability of organic cathode candidates and for
understanding electrochemically-induced structural transformations within organic
molecular crystals. Herein we explore the electrochemical lithiation-induced
polymorphism of anthraquinone (AQ) and three related derivatives. We believe that
this analysis can serve as a model for studying organic charge storage within
crystalline small-molecule candidates.
PMID- 26427625
TI - Development of a framework for genotyping bovine-derived Cryptosporidium parvum,
using a multilocus fragment typing tool.
AB - BACKGROUND: There is a need for an integrated genotyping approach for C. parvum;
no sufficiently discriminatory scheme to date has been fully validated or widely
adopted by veterinary or public health researchers. Multilocus fragment typing
(MLFT) can provide good differentiation and is relatively quick and cheap to
perform. A MLFT tool was assessed in terms of its typeability, specificity,
precision (repeatability and reproducibility), accuracy and ability to
genotypically discriminate bovine-derived Cryptosporidium parvum. METHODS: With
the aim of working towards a consensus, six markers were selected for inclusion
based on their successful application in previous studies: MM5, MM18, MM19, TP14,
MS1 and MS9. Alleles were assigned according to the fragment sizes of repeat
regions amplified, as determined by capillary electrophoresis. In addition, a
region of the GP60 gene was amplified and sequenced to determine gp60 subtype and
this was added to the allelic profiles of the 6 markers to determine the
multilocus genotype (MLG). The MLFT tool was applied to 140 C. parvum samples
collected in two cross-sectional studies of UK calves, conducted in Cheshire in
2004 (principally dairy animals) and Aberdeenshire/Caithness in 2011 (beef
animals). RESULTS: Typeability was 84 %. The primers did not amplify tested non
parvum species frequently detected in cattle. In terms of repeatability, within-
and between-run fragment sizes showed little variability. Between laboratories,
fragment sizes differed but allele calling was reproducible. The MLFT had good
discriminatory ability (Simpson's Index of Diversity, SID, was 0.92), compared to
gp60 sequencing alone (SID 0.44). Some markers were more informative than others,
with MS1 and MS9 proving monoallelic in tested samples. CONCLUSIONS: Further
inter-laboratory trials are now warranted with the inclusion of human-derived C.
parvum samples, allowing progress towards an integrated, standardised typing
scheme to enable source attribution and to determine the role of livestock in
future outbreaks of human C. parvum.
PMID- 26427627
TI - The effect of Varenicline on smoking cessation in a group of young asthma
patients.
AB - BACKGROUND: Tobacco use causes long-term morbidity and mortality. In patients
with asthma, the frequency of smokers is high; however, asthmatic smokers
experience more pronounced symptoms, accelerated loss of lung function and
treatment resistance. Varenicline is an effective drug in smoking cessation, when
investigated in COPD patients and general populations. The aim of the present
study was to evaluate the effect of Varenicline on tobacco cessation in young
asthmatics. METHODS: In a randomized, placebo-controlled, double-blinded trial,
52 asthmatic current smokers (age 19-40) >= 10 cigarettes daily and >=10
packyears (mean 15.6) were recruited to a 12 week treatment period with
Varenicline or placebo (1:1) in parallel design. Evaluation of smoking status,
asthma symptom score, general health quality score and methacholine challenge
were performed at week 0, week 6, week 12 and week 24. RESULTS: In the
Varenicline group, at week 12, 69% of the patients quit smoking vs. 36% in the
placebo group (p = 0.017, intended-to-treat analysis), but after 24 weeks, a high
relapse rate was present (quit rates 19% vs. 16%, NS). After 6 weeks of
treatment, significant improvements in airway hyperresponsiveness (AHR) in the
Varenicline group was found (from 88% to 58%, p = 0.016), whereas no change was
observed in the placebo group. Symptom score and general health quality improved
in both the Varenicline and the placebo group. CONCLUSION: We demonstrated that
Varenicline can be used with a high probability of success with tobacco cessation
in young smokers with asthma, but relapse rate after end of treatment is high.
Quitting smoking can improve asthma control.
PMID- 26427628
TI - Validation of human small airway measurements using endobronchial optical
coherence tomography.
AB - BACKGROUND: Small airway remodeling is the cardinal feature underlying chronic
airway diseases. There is no modality which identifies small airway pathological
changes, which is crucial for early diagnosis, efficacy and prognostic
assessment. OBJECTIVE: To evaluate the usefulness of endobronchial optical
coherence tomography (EB-OCT) in assessing small airways morphology in vivo.
METHODS: Twelve patients with pulmonary nodules scheduled for lung resection
underwent spirometry, multi-detector computed tomography (MDCT) and EB-OCT. We
measured D(mean) (mean luminal diameter), Ai (inner luminal area), Aw (airway
wall area) and Aw% [Aw/(Ai + Aw) * 100%] from the 3rd to 5th generation bronchi
of RB9 segment by MDCT. D(mean), Ai, Aw and Aw% from the 3rd to 9th generation
bronchi of RB9 segment were measured by EB-OCT and histology. Correlations of
these parameters, measured by three different methods, were evaluated. We
recruited 4 COPD patients to determine if EB-OCT could identify peripheral airway
remodeling. RESULTS: The 4 parameters, measured by CT and EB-OCT, correlated
significantly [D(mean) (r = 0.991), Ai (r = 0.997), Aw (r = 0.997), Aw% (r =
0.991), all P < 0.01]. Significant correlation were found for these parameters,
measured by histology and EB-OCT, from the 3rd to 5th generation bronchi [D(mean)
(r = 0.989), Ai (r = 0.997), Aw (r = 0.999), Aw% (r = 0.988), all P < 0.01], and
from the 6th to 9th generation bronchi [D(mean) (r = 0.979), Ai (r = 0.997), Aw
(r = 0.994) and Aw% (r = 0.988), all P < 0.01]. Significant small airways
morphological abnormalities were observed in COPD patients. CONCLUSIONS: EB-OCT,
a minimally invasive imaging modality with high-resolution, is useful and
clinically practical for assessing proximal and distal airways of human compared
with CT and histology.
PMID- 26427629
TI - Does Femoroacetabular Impingement Cause Hip Instability? A Systematic Review.
AB - PURPOSE: To determine whether femoroacetabular impingement (FAI) is associated
with hip instability. METHODS: A systematic search examining FAI and hip
instability was conducted according to Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) guidelines. Clinical and basic science studies
were included. Instability had to be documented with either a clinical or imaging
examination. Studies were excluded if they did not define diagnostic criteria for
FAI, involved prosthetic hips, were not in English, were review articles, or
reported Level V evidence (case reports, expert opinion). Rates of FAI
morphologic features in patients with documented hip instability were determined.
Mechanisms and rates of FAI-induced hip subluxation were examined in basic
science studies. RESULTS: The search yielded 1,630 relevant studies. Seven
studies (4 clinical and 3 basic science) met inclusion criteria. Four studies
investigated an association between FAI and hip instability in 92 patients with
an average age of 31 years. Seventy-six patients experienced frank dislocations
and 16 experienced posterior subluxation events. The prevalence of FAI was
documented in 89 patients with hip instability. The rates of cam and pincer
morphologic characteristics were 74% and 64%, respectively. The average lateral
center edge angle and prevalence of acetabular retroversion were 30 degrees and
70%, respectively (n = 76 patients). All 3 basic science studies had real-time
visualization of FAI-induced hip subluxations. CONCLUSIONS: High rates of FAI
morphologic characteristics are present in patients with hip instability. FAI
morphologic characteristics may predispose the hip to instability through
anatomic conflict caused by pincer or cam lesions (or both) levering the femoral
head posteriorly. LEVEL OF EVIDENCE: Level IV, systematic review of Level III,
Level IV, and non-clinical studies.
PMID- 26427630
TI - Bone-Patellar Tendon-Bone Versus Soft-Tissue Allograft for Anterior Cruciate
Ligament Reconstruction: A Systematic Review.
AB - PURPOSE: To describe the outcomes of bone-patellar tendon-bone (BPTB) and soft
tissue allografts in anterior cruciate ligament (ACL) reconstruction with respect
to graft failure risk, physical examination findings, instrumented laxity, and
patient-reported outcomes. METHODS: A search of the PubMed, Scopus, CINAHL
(Cumulative Index to Nursing and Allied Health Literature) Complete, Cochrane
Collaboration, and SPORTDiscus databases was performed. English-language studies
with outcome data on primary ACL reconstruction with nonirradiated BPTB and soft
tissue allografts were identified. Outcome data included failure risk, physical
examination findings, instrumented laxity measurements, and patient-reported
outcome scores. RESULTS: Seventeen studies met the inclusion criteria. Of these
studies, 11 reported on BPTB allografts exclusively, 5 reported on soft-tissue
allografts exclusively, and 1 compared both types. The comparative study showed
no difference in failure risk, Lachman grade, pivot-shift grade, instrumented
laxity, or overall International Knee Documentation Committee score between the 2
allograft types. Data from all studies yielded a failure risk of 10.3% (95%
confidence interval [CI], 4.5% to 18.1%) in the soft-tissue group and 15.2% (95%
CI, 11.3% to 19.6%) in the BPTB group. The risk of a Lachman grade greater than 5
mm was 6.4% (95% CI, 1.7% to 13.7%) in the soft-tissue group and 8.6% (95% CI,
6.3% to 11.2%) in the BPTB group. The risk of a grade 2 or 3 pivot shift was 1.4%
(95% CI, 0.3% to 3.3%) in the soft-tissue group and 4.1% (95% CI, 1.9% to 7.2%)
in the BPTB group. CONCLUSIONS: One comparative study showed no difference in
results after ACL reconstruction with nonirradiated BPTB and soft-tissue
allografts. Inclusion of case series in the analysis showed qualitatively similar
outcomes with the 2 graft types.
PMID- 26427631
TI - Systematic Review of Biceps Tenodesis: Arthroscopic Versus Open.
AB - PURPOSE: We present a systematic review of the recent literature regarding the
use of arthroscopic and open methods of tenodesis for lesions of the long head of
the biceps brachii and present an analysis of the subjective and objective
outcomes after these 2 procedures. METHODS: PubMed was carefully reviewed for
suitable articles relating to biceps tenodesis, both open and arthroscopic. We
included studies reporting on the clinical outcomes of these 2 procedures that
were of Level I to IV evidence and were published in the English language. The
primary clinical outcomes for each study were determined, normalized, and
reported as the percentage of good or excellent results versus poor results based
on the outcome scores and criteria laid out by the authors in each of the
studies. The exclusion criteria included studies in which biceps tenodesis was
performed in patients with concomitant rotator cuff repairs, nonhuman studies,
and biomechanical studies. RESULTS: A total of 16 studies met our inclusion
criteria. Among all studies, a total of 205 arthroscopic tenodesis procedures and
a total of 271 open tenodesis procedures were performed. Among the 271 open
tenodesis patients, 98% had a good or excellent outcome, with a poor outcome in 5
patients (2%). Among the 205 patients who underwent arthroscopic tenodesis, 98%
had a good or excellent outcome, with a poor outcome in 5 patients (2%).
CONCLUSIONS: Both open and arthroscopic biceps tenodesis provided satisfactory
outcomes in most patients, and there were no identifiable differences in this
review.
PMID- 26427632
TI - Effect of the Osteotomy Length on the Change of the Posterior Tibial Slope With a
Simple Distraction of the Posterior Gap in the Uni- and Biplanar Open-Wedge High
Tibial Osteotomy.
AB - PURPOSE: To (1) determine the length of the osteotomy at the anterior and
posterior cortex, (2) compare between uni- and biplanar osteotomy, and (3)
evaluate the relationship between the extent of the osteotomy and change of the
posterior tibial slope. METHODS: A prospective comparative study of 24 uniplanar
and 30 biplanar osteotomies was performed. To evaluate the length of osteotomy,
osteotomy lines of the anterior and posterior cortex were analyzed in the 3
dimensional surface models. For slope measurement, the intramedullary axis of the
proximal tibia (slope P), posterior cortical line of the proximal tibia (slope
C), and anterior cortical line of the proximal fibula (slope F) were used. An
analysis of the changes in the posterior tibial slope was performed independently
using a pre- and postoperative lateral plane radiograph. RESULTS: In the
uniplanar osteotomy, ratios of the osteotomized length to the total cortical
length aligned with the osteotomized plane were larger in the anterior cortex
(0.91 in uniplanar v 0.46 in biplanar; P = 0) and posterior cortex (0.97 in
uniplanar v 0.79 ratio in biplanar; P = 0). Furthermore, the posterior tibial
slope was maintained in both groups and the ratios between the anterior and
posterior gap in both groups were 0.57 and 0.63, respectively. The maintenance of
the slope was not related to any specific variables. Additionally, these
phenomena did not differ between those patients who underwent uni- and those who
underwent biplanar osteotomy. CONCLUSIONS: Increase in the posterior tibial slope
was prevented with appropriate uni- or biplanar osteotomy with a simple
distraction at the most posterior gap. However, in the uniplanar osteotomy, the
ratio of the osteotomized length to the total cortical length was larger in both
the anterior and posterior cortex.
PMID- 26427633
TI - Effects of different spray formulations on the reproductive parameters of
engorged Rhipicephalus (Boophilus) microplus females detached from experimentally
infested cattle.
AB - This present study aimed to evaluate the deleterious effects of some commercially
available spray formulations (15% Cypermethrin+25% Chlorpyriphos+1% Citronellal
and 8% Cypermethrin+60% Ethion) on the reproductive parameters of engorged
Rhipicephalus (Boophilus) microplus females that detached from experimentally
infested cattle. The following reproductive parameters of engorged female ticks
were analyzed: female weight, egg mass weight, percentage of hatchability,
percentage of reduction in oviposition, percentage of reduction in hatchability,
reproductive efficiency and percent control/efficacy of formulations for
reproductive parameters. Our findings showed that although the strain R. (B.)
microplus used in both experiments was thought to be sensitive to the test
compounds because of the acaricidal efficacy observed throughout these trials, it
was not possible to observe overall deleterious effects on the reproductive
parameters of this tick species with both spray formulations. However, the 8%
Cypermethrin+60% Ethion showed short-term significant effects on the weight of
female ticks between the 14th and 16th days post-treatment and the weight of
female and the egg mass weight between the 20th and 22nd days post-treatment. New
studies should be conducted to show if these results regarding the reproductive
parameters of fully engorged R. (B.) microplus females, combined with the
acaricidal efficacy can be sufficient to reduce the number of chemical treatments
administered to cattle.
PMID- 26427634
TI - Quantitative risk assessment of entry of contagious bovine pleuropneumonia
through live cattle imported from northwestern Ethiopia.
AB - Contagious bovine pleuropneumonia (CBPP) is a highly contagious bacterial disease
of cattle caused by Mycoplasma mycoides subspecies mycoides small colony (SC)
bovine biotype (MmmSC). It has been eradicated from many countries; however, the
disease persists in many parts of Africa and Asia. CBPP is one of the major trade
restricting diseases of cattle in Ethiopia. In this quantitative risk assessment
the OIE concept of zoning was adopted to assess the entry of CBPP into an
importing country when up to 280,000 live cattle are exported every year from the
northwestern proposed disease free zone (DFZ) of Ethiopia. To estimate the level
of risk, a six-tiered risk pathway (scenario tree) was developed, evidences
collected and equations generated. The probability of occurrence of the hazard at
each node was modelled as a probability distribution using Monte Carlo simulation
(@RISK software) at 10,000 iterations to account for uncertainty and variability.
The uncertainty and variability of data points surrounding the risk estimate were
further quantified by sensitivity analysis. In this study a single animal
destined for export from the northwestern DFZ of Ethiopia has a CBPP infection
probability of 4.76*10(-6) (95% CI=7.25*10(-8) 1.92*10(-5)). The probability that
at least one infected animal enters an importing country in one year is 0.53 (90%
CI=0.042-0.97). The expected number of CBPP infected animals exported any given
year is 1.28 (95% CI=0.021-5.42). According to the risk estimate, an average of
2.73*10(6) animals (90% CI=10,674-5.9*10(6)) must be exported to get the first
infected case. By this account it would, on average, take 10.15 years (90%
CI=0.24-23.18) for the first infected animal to be included in the consignment.
Sensitivity analysis revealed that prevalence and vaccination had the highest
impact on the uncertainty and variability of the overall risk.
PMID- 26427635
TI - Hyperostotic En Plaque Meningioma Mimicking Fibrous Dysplasia of the Temporal
Bone.
PMID- 26427636
TI - The Natural History and Management of Petrous Apex Cholesterol Granulomas.
AB - OBJECTIVE: To evaluate the clinical and radiographic characteristics of
cholesterol granulomas of the petrous apex, as well as the outcomes of operative
and conservative management. STUDY DESIGN: Retrospective chart review. SETTING:
Two independent tertiary academic referral centers. PATIENTS: Adult and pediatric
patients with cholesterol granulomas of the petrous apex were identified from the
experience of two separate centers. Patients were included after radiographic
diagnosis and clinical evaluation. All patients with less than 6 months of follow
up and those with iatrogenic postoperative cholesterol granulomas were excluded.
INTERVENTION: Demographic information, presenting symptoms, imaging
characteristics, treatment strategies, and outcomes were recorded. MAIN OUTCOME
MEASURES: Patients were evaluated on the basis of symptom and radiographic
evolution during time, with or without operative intervention. RESULTS: Ninety
petrous apex cholesterol granulomas were analyzed (57.8% females, 55.6% right
sided). The average age at presentation was 43.1 years (median 42.0, range 8.0
77.0 years). The most common presenting symptom was headache (56.7%), and the
average lesion size in the greatest dimension was 2.1 cm (median 1.7, range 0.7
5.0 cm). During a mean follow-up of 46.0 months, no cases of spontaneous rupture
or carotid injury occurred. Twenty-three patients (25.6%) ultimately underwent
surgical management, most commonly for intractable headache, and only 47.8% of
these patients experienced durable symptom improvement by their last
postoperative follow-up. CONCLUSION: Many cholesterol granulomas of the petrous
apex remain stable during time and can be safely managed with primary
observation. Surgery should be reserved for lesions that are causing, or
threatening, neurologic dysfunction because of mass effect or erosion of critical
structures such as the otic capsule. Cranial neuropathy associated with
cholesterol granuloma may improve after operative management; however, symptoms
such as headache and dizziness are less likely to benefit from surgery. As a
general guideline, in the presence of a radiologically stable cholesterol
granuloma in the petrous apex, alternative etiologies for headache and dizziness
should be considered and treated before offering surgical intervention.
PMID- 26427637
TI - Speech Intelligibility in Noise With a Pinna Effect Imitating Cochlear Implant
Processor.
AB - OBJECTIVE: To evaluate the speech intelligibility in noise with a new cochlear
implant (CI) processor that uses a pinna effect imitating directional microphone
system. STUDY DESIGN: Prospective experimental study. SETTING: Tertiary referral
center. PATIENTS: Ten experienced, unilateral CI recipients with bilateral severe
to-profound hearing loss.Intervention: All participants performed speech in noise
tests with the Opus 2 processor (omnidirectional microphone mode only) and the
newer Sonnet processor (omnidirectional and directional microphone mode). MAIN
OUTCOME MEASURE: The speech reception threshold (SRT) in noise was measured in
four spatial settings. The test sentences were always presented from the front.
The noise was arriving either from the front (S0N0), the ipsilateral side of the
CI (S0NIL), the contralateral side of the CI (S0NCL), or the back (S0N180).
RESULTS: The directional mode improved the SRTs by 3.6 dB (p < 0.01), 2.2 dB (p <
0.01), and 1.3 dB (p < 0.05) in the S0N180, S0NIL, and S0NCL situations, when
compared with the Sonnet in the omnidirectional mode. There was no statistically
significant difference in the S0N0 situation. No differences between the Opus 2
and the Sonnet in the omnidirectional mode were observed. CONCLUSION: Speech
intelligibility with the Sonnet system was statistically different to speech
recognition with the Opus 2 system suggesting that CI users might profit from the
pinna effect imitating directionality mode in noisy environments.
PMID- 26427624
TI - Patients with coronary artery disease and diabetes need improved management: a
report from the EUROASPIRE IV survey: a registry from the EuroObservational
Research Programme of the European Society of Cardiology.
AB - BACKGROUND: In order to influence every day clinical practice professional
organisations issue management guidelines. Cross-sectional surveys are used to
evaluate the implementation of such guidelines. The present survey investigated
screening for glucose perturbations in people with coronary artery disease and
compared patients with known and newly detected type 2 diabetes with those
without diabetes in terms of their life-style and pharmacological risk factor
management in relation to contemporary European guidelines. METHODS: A total of
6187 patients (18-80 years) with coronary artery disease and known glycaemic
status based on a self reported history of diabetes (previously known diabetes)
or the results of an oral glucose tolerance test and HbA1c (no diabetes or newly
diagnosed diabetes) were investigated in EUROASPIRE IV including patients in 24
European countries 2012-2013. The patients were interviewed and investigated in
order to enable a comparison between their actual risk factor control with that
recommended in current European management guidelines and the outcome in
previously conducted surveys. RESULTS: A total of 2846 (46%) patients had no
diabetes, 1158 (19%) newly diagnosed diabetes and 2183 (35%) previously known
diabetes. The combined use of all four cardioprotective drugs in these groups was
53, 55 and 60%, respectively. A blood pressure target of <140/90 mmHg was
achieved in 68, 61, 54% and a LDL-cholesterol target of <1.8 mmol/L in 16, 18 and
28%. Patients with newly diagnosed and previously known diabetes reached an HbA1c
<7.0% (53 mmol/mol) in 95 and 53% and 11% of those with previously known diabetes
had an HbA1c >9.0% (>75 mmol/mol). Of the patients with diabetes 69% reported on
low physical activity. The proportion of patients participating in cardiac
rehabilitation programmes was low (~40 %) and only 27% of those with diabetes had
attended diabetes schools. Compared with data from previous surveys the use of
cardioprotective drugs had increased and more patients were achieving the risk
factor treatment targets. CONCLUSIONS: Despite advances in patient management
there is further potential to improve both the detection and management of
patients with diabetes and coronary artery disease.
PMID- 26427638
TI - REM sleep Behaviour Disorder.
AB - Rapid Eye Movement (REM) sleep Behaviour Disorder (RBD) is a REM sleep parasomnia
characterized by loss of the muscle atonia that typically occurs during REM
sleep, therefore allowing patients to act out their dreams. RBD manifests itself
clinically as a violent behaviour occurring during the night, and is detected at
the polysomnography by phasic and/or tonic muscle activity on the
electromyography channel. In absence of neurological signs or central nervous
system lesions, RBD is defined as idiopathic. Nevertheless, in a large number of
cases the development of neurodegenerative diseases in RBD patients has been
described, with the duration of the follow-up representing a fundamental aspect.
A growing number of clinical, neurophysiologic and neuropsychological studies
aimed to detect early markers of neurodegenerative dysfunction in RBD patients.
Anyway, the evidence of impaired cortical activity, subtle neurocognitive
dysfunction, olfactory and autonomic impairment and neuroimaging brain changes in
RBD patients is challenging the concept of an idiopathic form of RBD, supporting
the idea of RBD as an early manifestation of a more complex neurodegenerative
process.
PMID- 26427640
TI - Intertemporal choice in Parkinson's disease and restless legs syndrome.
AB - BACKGROUND: Impulse control disorders in Parkinson's disease are a potential
consequence of dopaminergic therapy. Impulse control problems might be revealed
by intertemporal choice tasks which entail to forgo an immediately available
reward in favor of a larger but later reward. The steepness of the discounting
curve can be quantified by the parameter k. METHODS: Participants (37 Parkinson
patients [13 de novo, 24 medicated], 24 patients with restless legs syndrome, and
22 controls) were offered 54 choices between immediate smaller rewards and
delayed larger and the k value was estimated from the participants' responses.
Participants had the chance of winning one of their decisions. None of the
participants had impulse control disorders. RESULTS: Unmedicated Parkinson
patients had a higher discounting rate than controls and medicated patients with
restless legs syndrome. The k values of medicated Parkinson patients and patients
with restless legs syndrome did not differ from those of controls. No correlation
was found between the k value and the dopamine agonist dose. CONCLUSION:
Impulsive decision making in patients with Parkinson's disease may occur as part
of the disease rather than as a consequence of dopamine agonist therapy.
PMID- 26427639
TI - Psychogenic and neural visual-cue response in PD dopamine dysregulation syndrome.
AB - INTRODUCTION: Dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD)
patients refers to the compulsive use of dopaminergic replacement therapy and has
serious psycho-social consequences. Mechanisms underlying DDS are not clear
although has been linked to dysfunctional brain reward networks. METHODS: With
fMRI, we investigate behavioral and neural response to drug-cues in six PD DDS
patients and 12 PD control patients in both the ON and OFF medication state.
Behavioral measures of liking, wanting and subjectively 'feeling ON medication'
were also collected. RESULTS: Behaviorally, PD DDS patients feel less ON and want
their drugs more at baseline compared to PD controls. Following drug-cue
exposure, PD DDS patients feel significantly more ON medication, which correlates
with significant increases in reward related regions. CONCLUSIONS: The results
demonstrate that exposure to drug-cues increases the subjective feeling of being
'ON' medication which corresponds to dysfunctional activation in reward related
regions in PD DDS patients. These findings should be extended in future studies.
Visual stimuli being sufficient to elicit behavioral response through
neuroadaptations could have direct implications to the management of addictive
behavior.
PMID- 26427641
TI - Reduced early dried blood spot citrulline levels in preterm infants with meconium
obstruction of prematurity.
AB - BACKGROUND: Citrulline is a non-protein amino acid synthesized in the enterocytes
of the small bowel. Recent studies have reported that plasma citrulline levels
correlate with functional enterocyte mass. AIMS: This study aimed to determine
the normal dried blood spot (DBS) citrulline levels and to determine the
existence of a correlation between citrulline levels and meconium obstruction of
prematurity (MOP). STUDY DESIGN AND SUBJECTS: A retrospective cohort study was
performed involving 285 infants born at less than 32weeks gestation who were
admitted to the neonatal intensive care unit between Oct 2009 and Aug 2014.
OUTCOME MEASURES: We analyzed the DBS citrulline levels, which are routinely
measured via newborn screening at 7days following birth, using liquid
chromatography-MS/MS. We investigated the relationship between DBS citrulline
levels and clinical parameters such as gestational age (GA), body measurements at
birth, gender, or the presence or absence of either necrotizing enterocolitis or
MOP. RESULTS: A total of 229 infants with a median GA of 29.6weeks and a median
birth weight of 1160g were included. DBS citrulline levels were not associated
with GA, body measurements at birth or gender. DBS citrulline levels were
significantly decreased when patients presented with MOP (p=0.037). CONCLUSIONS:
Early DBS citrulline levels were not associated with either GA or body
measurements at birth but were reduced among preterm infants with MOP compared
with the control infants. These results may be indicative of abnormal fetal
intestinal development and reduced functional enterocyte mass among preterm
infants with MOP.
PMID- 26427643
TI - Temporal dynamics of visual working memory.
AB - The involvement of the human cerebellum in working memory has been well
established in the last decade. However, the cerebro-cerebellar network for
visual working memory is not as well defined. Our previous fMRI study showed
superior and inferior cerebellar activations during a block design visual working
memory task, but specific cerebellar contributions to cognitive processes in
encoding, maintenance and retrieval have not yet been established. The current
study examined cerebellar contributions to each of the components of visual
working memory and presence of cerebellar hemispheric laterality was
investigated. 40 young adults performed a Sternberg visual working memory task
during fMRI scanning using a parametric paradigm. The contrast between high and
low memory load during each phase was examined. We found that the most prominent
activation was observed in vermal lobule VIIIb and bilateral lobule VI during
encoding. Using a quantitative laterality index, we found that left-lateralized
activation of lobule VIIIa was present in the encoding phase. In the maintenance
phase, there was bilateral lobule VI and right-lateralized lobule VIIb activity.
Changes in activation in right lobule VIIIa were present during the retrieval
phase. The current results provide evidence that superior and inferior cerebellum
contributes to visual working memory, with a tendency for left-lateralized
activations in the inferior cerebellum during encoding and right-lateralized
lobule VIIb activations during maintenance. The results of the study are in
agreement with Baddeley's multi-component working memory model, but also suggest
that stored visual representations are additionally supported by maintenance
mechanisms that may employ verbal coding.
PMID- 26427644
TI - Stratified mixture modeling for segmentation of white-matter lesions in brain MR
images.
AB - Accurate characterization of white-matter lesions from magnetic resonance (MR)
images has increasing importance for diagnosis and management of treatment of
certain neurological diseases, and can be performed in an objective and effective
way by automated lesion segmentation. This usually involves modeling the whole
brain MR intensity distribution, however, capturing various sources of MR
intensity variability and lesion heterogeneity results in highly complex whole
brain MR intensity models, thus their robust estimation on a large set of MR
images presents a huge challenge. We propose a novel approach employing
stratified mixture modeling, where the main premise is that the otherwise complex
whole-brain model can be reduced to a tractable parametric form in small brain
subregions. We show on MR images of multiple sclerosis (MS) patients with
different lesion loads that robust estimators enable accurate mixture modeling of
MR intensity in small brain subregions even in the presence of lesions.
Recombination of the mixture models across strata provided an accurate whole
brain MR intensity model. Increasing the number of subregions and, thereby, the
model complexity, consistently improved the accuracy of whole-brain MR intensity
modeling and segmentation of normal structures. The proposed approach was
incorporated into three unsupervised lesion segmentation methods and, compared to
original and three other state-of-the-art methods, the proposed modeling approach
significantly improved lesion segmentation according to increased Dice similarity
indices and lower number of false positives on real MR images of 30 patients with
MS.
PMID- 26427642
TI - Generative models of the human connectome.
AB - The human connectome represents a network map of the brain's wiring diagram and
the pattern into which its connections are organized is thought to play an
important role in cognitive function. The generative rules that shape the
topology of the human connectome remain incompletely understood. Earlier work in
model organisms has suggested that wiring rules based on geometric relationships
(distance) can account for many but likely not all topological features. Here we
systematically explore a family of generative models of the human connectome that
yield synthetic networks designed according to different wiring rules combining
geometric and a broad range of topological factors. We find that a combination of
geometric constraints with a homophilic attachment mechanism can create synthetic
networks that closely match many topological characteristics of individual human
connectomes, including features that were not included in the optimization of the
generative model itself. We use these models to investigate a lifespan dataset
and show that, with age, the model parameters undergo progressive changes,
suggesting a rebalancing of the generative factors underlying the connectome
across the lifespan.
PMID- 26427645
TI - Neural structures involved in visual search guidance by reward-enhanced
contextual cueing of the target location.
AB - Spatial contextual cueing reflects an incidental form of learning that occurs
when spatial distractor configurations are repeated in visual search displays.
Recently, it was reported that the efficiency of contextual cueing can be
modulated by reward. We replicated this behavioral finding and investigated its
neural basis with fMRI. Reward value was associated with repeated displays in a
learning session. The effect of reward value on context-guided visual search was
assessed in a subsequent fMRI session without reward. Structures known to support
explicit reward valuation, such as ventral frontomedial cortex and posterior
cingulate cortex, were modulated by incidental reward learning. Contextual
cueing, leading to more efficient search, went along with decreased activation in
the visual search network. Retrosplenial cortex played a special role in that it
showed both a main effect of reward and a reward*configuration interaction and
may thereby be a central structure for the reward modulation of context-guided
visual search.
PMID- 26427646
TI - Estimation of the Survival of Patients With Lung Squamous Cell Carcinoma Using
Genomic Copy Number Aberrations.
AB - BACKGROUND: Estimation of the survival of patients with lung squamous cell
carcinoma (SCC) on the basis of histopathology is inadequate. The aim of this
study was to identify genomic regions with potential value for estimating the
prognosis of these patients. PATIENTS AND METHODS: Depending on their survival
time, 100 patients with primary lung SCC were separated into high- or low-risk
prognostic groups, and their copy number aberrations (CNAs) were analyzed using
array-comparative genomic hybridization (array-CGH). RESULTS: We identified 123
CNA regions that were significantly associated with survival. Among these
regions, some have been reported previously (eg, amplifications of 8p12, 3q27.1,
and loss of 9p21.3 and 13q34) but others have never been reported. For example,
gains of 3q27.1, 5p13.2, and 5p13.3 were found to be associated with a favorable
prognosis, but patients harboring gains of 11q23.3, 11q13.1, and 14q32.3, and
deletions of 3p21.3 and 9p21.3 tended to have poor survival. Among the 123 CNA
regions, 41 were further selected to construct a survival estimation model that
could effectively separate SCC patients into high- or low-risk groups with an
accuracy of 92%, sensitivity of 90%, and specificity of 94%. The results of the
array-CGH were further validated in an independent cohort of 45 formalin-fixed,
paraffin-embedded specimens using real-time polymerase chain reaction.
CONCLUSION: A number of CNA regions were found to be associated with the survival
of SCC patients, and we were able to construct a model to estimate prognosis on
the basis of these regions. Assessment of these CNAs could potentially assist in
clinical decision-making regarding adjuvant therapy after surgery.
PMID- 26427647
TI - Renin-Angiotensin System Inhibitors Might Help to Reduce the Development of
Symptomatic Radiation Pneumonitis After Stereotactic Body Radiotherapy for Lung
Cancer.
AB - INTRODUCTION: The purpose of the present study was to evaluate the role of renin
angiotensin system (RAS) inhibitors in preventing symptomatic radiation
pneumonitis (RP) after stereotactic body radiotherapy (SBRT). MATERIALS AND
METHODS: The data from 158 patients with a solitary lung lesion treated with 1 to
3 fractions of SBRT from December 2008 to July 2014 were retrospectively
analyzed. The incidence of RP was evaluated according to the Common Toxicity
Criteria for Adverse Events, version 4. The use of angiotensin-converting enzyme
inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) was analyzed to
assess for possible correlations with the development of grade >= 2 RP. The
patient and dosimetric variables were also assessed. RESULTS: After a median
follow-up period of 13.8 months (range, 3.2-55.0 months), 22 patients had
developed grade >= 2 RP. Patients with peripheral lesions, favorable dosimetric
data, and ACEI and/or ARB use had a reduced risk of symptomatic RP. In unadjusted
and adjusted multivariate analyses, ACEI and/or ARB intake and the dosimetric
variables were statistically significant factors. In a secondary analysis, the
use of ACEIs and ARBs among patients with a greater planning target volume and
higher dosimetric values correlated with a reduced risk of symptomatic RP.
CONCLUSION: The use of a RAS inhibitor was associated with a decreased incidence
of symptomatic RP among patients undergoing SBRT for lung lesions. Patients with
higher dosimetric values had a reduced risk of grade >= 2 RP with ACEI and ARB
use.
PMID- 26427648
TI - Potential of carboxymethyl cellulose and gamma-irradiation to maintain quality
and control disease of peach fruit.
AB - Carboxymethyl cellulose (CMC) coatings alone and in combination with gamma
irradiation were tested for maintaining the storage quality and control of post
harvest gray and black mold disease of peach. Matured green peaches were CMC
coated at levels 0.5-1.0% (w/v) and gamma irradiated at 1.2 kGy. The treated
fruit including control was stored under ambient (temperature 25 +/- 2 degrees C,
RH 70%) and refrigerated (temperature 3 +/- 1 degrees C, RH 80%) conditions. In
fruits treated with individual treatments of 1.0% (w/v) CMC; 1.2 kGy irradiation
and combination of 1.0% (w/v) CMC and 1.2 kGy irradiation, no decay was recorded
up to 6, 8 and 14 days of ambient storage. Irradiation alone at 1.2 kGy prevented
the onset of disease incidence up to 4 days compared to 2 days by 1.0% (w/v) CMC
coating following 30 days of refrigeration. Combination of CMC at 1.0% (w/v) and
1.2 kGy irradiation prevented disease incidence of peach up to 7 days during post
refrigerated storage at 25 +/- 2 degrees C, RH 70% following 30 days of
refrigeration. Above combinatory treatment can be of great potential in
facilitating the marketing of the fruit, thereby benefiting the growers.
PMID- 26427649
TI - Tensin1 positively regulates RhoA activity through its interaction with DLC1.
AB - DLC1 is a RhoGAP-containing tumor suppressor and many of DLC1's functions are
absolutely dependent on its RhoGAP activity. Through its RhoGAP domain, DLC1
inhibits the activity of RhoA GTPase, which regulates actin cytoskeleton networks
and dis/assembly of focal adhesions. Tensin1 (TNS1) is a focal adhesion molecule
that links the actin cytoskeleton to integrins and forms signaling complexes
through its multiple binding domains. Here, we report that TNS1 enhances RhoA
activity in a DLC1-dependent manner. This is accomplished by binding to DLC1
through TNS1's C2, SH2, and PTB domains. Point mutations at these three sites
disrupt TNS1's interaction with DLC1 as well as its effect on RhoA activity. The
biological relevance of this TNS1-DLC1-RhoA signaling axis is investigated in
TNS1 knockout (KO) cells and mice. Endothelial cells isolated from TNS1 KO mice
or those silenced with TNS1 siRNA show significant reduction in proliferation,
migration, and tube formation activities. Concomitantly, the RhoA activity is
down-regulated in TNS1 KO cells and this reduction is restored by further
silencing of DLC1. Furthermore, the angiogenic process is compromised in TNS1 KO
mice. These studies demonstrate that TNS1 binds to DLC1 and fine-tunes its RhoGAP
activity toward RhoA and that the TNS1-DLC1-RhoA signaling axis is critical in
regulating cellular functions that lead to angiogenesis.
PMID- 26427650
TI - Amphiregulin lacks an essential role for the bone anabolic action of parathyroid
hormone.
AB - Although parathyroid hormone (PTH) has long been known to act as a bone anabolic
agent when administered intermittently, the exact underlying mechanisms remain
largely unknown. Amphiregulin (AREG), a ligand of the epidermal growth factor
receptor, has been identified to be a PTH target gene in vitro and in vivo. Here,
we used female global AREG knockout (AREG-KO) mice to explore the role of AREG in
mediating the bone anabolic effects of PTH. AREG-KO mice were characterized by
unchanged distal femoral cancellous bone mass and only subtle decreases in bone
mineral density (BMD) and cortical thickness at the femoral midshaft at 3 and 8
months of age, relative to wildtype controls. AREG deficiency was associated with
complex changes in the mRNA expression of other EGFR ligands in femoral
cancellous bone osteoblasts in situ in 3-week-old mice. To examine the bone
anabolic effects of PTH in the absence and presence of AREG, we injected 3-month
old AREG-KO females and wildtype control littermates with 80 MUg/kg PTH or
vehicle 5 times per week over 4 weeks. Intermittent PTH treatment of AREG-KO mice
led to increases in femoral trabecular and cortical BMD, cortical thickness,
endocortical and periosteal bone formation, cancellous bone formation rate, and
serum osteocalcin, comparable to those observed in wildtype control mice. In
conclusion, our data indicate that the bone anabolic effects of PTH do not
require AREG, at least in 3-month-old female mice.
PMID- 26427651
TI - Developmental exposure to bisphenol A alters expression and DNA methylation of
Fkbp5, an important regulator of the stress response.
AB - Bisphenol A (BPA), an abundant endocrine disruptor, affects stress-responsiveness
and related behaviors in children. In rats, perinatal BPA exposure modifies
stress response in pubertal offspring via unknown mechanisms. Here we examined
possible epigenetic modifications in the glucocorticoid receptor gene and its
regulator Fkbp5 in hypothalamus and hippocampus of exposed offspring. We found
increased DNA methylation of Fkbp5 and reduced protein levels in the hippocampus
of exposed male rats. Similar effects were obtained in a male hippocampal cell
line when exposed to BPA during differentiation. The estrogen receptor (ER)
antagonist ICI 182,780 or ERbeta knock-down affected Fkbp5 expression and
methylation similarly to BPA. Further, BPA's effect on Fkbp5 was abolished upon
knock-down of ERbeta, suggesting a role for this receptor in mediating BPA's
effects on Fkbp5. These data demonstrate that developmental BPA exposure modifies
Fkbp5 methylation and expression in male rats, which may be related to its impact
on stress responsiveness.
PMID- 26427653
TI - Genome-wide association studies of human adiposity: Zooming in on synapses.
AB - The decade anniversary for genome-wide association studies (GWAS) is approaching,
and this experimental approach has commenced a deeper understanding of the
genetics underlying complex diseases. In obesity genetics the GIANT (Genetic
Investigation of ANthropometric Traits) consortium has played a crucial role,
recently with two comprehensive meta-analyses, one focusing on general obesity,
analyzing body-mass index (BMI) and the other on fat distribution, focusing on
waist-hip ratio adjusted for BMI. With the in silico methods applied in these two
studies as the pivot, this review looks into some of the biological knowledge,
beginning to emerge from the intricate genomic background behind the genetic
determinants of human adiposity. These include synaptic dysfunction, where GWAS
pinpoint potential new mechanisms in pathways already known to be linked with
obesity.
PMID- 26427652
TI - Lxr regulates lipid metabolic and visual perception pathways during zebrafish
development.
AB - The Liver X Receptors (LXRs) play important roles in multiple metabolic pathways,
including fatty acid, cholesterol, carbohydrate and energy metabolism. To expand
the knowledge of the functions of LXR signaling during embryonic development, we
performed a whole-genome microarray analysis of Lxr target genes in zebrafish
larvae treated with either one of the synthetic LXR ligands T0901317 or GW3965.
Assessment of the biological processes enriched by differentially expressed genes
revealed a prime role for Lxr in regulating lipid metabolic processes, similarly
to the function of LXR in mammals. In addition, exposure to the Lxr ligands
induced changes in expression of genes in the neural retina and lens of the
zebrafish eye, including the photoreceptor guanylate cyclase activators and lens
gamma crystallins, suggesting a potential novel role for Lxr in modulating the
transcription of genes associated with visual function in zebrafish. The
regulation of expression of metabolic genes was phenotypically reflected in an
increased absorption of yolk in the zebrafish larvae, and changes in the
expression of genes involved in visual perception were associated with
morphological alterations in the retina and lens of the developing zebrafish eye.
The regulation of expression of both lipid metabolic and eye specific genes was
sustained in 1 month old fish. The transcriptional networks demonstrated several
conserved effects of LXR activation between zebrafish and mammals, and also
identified potential novel functions of Lxr, supporting zebrafish as a promising
model for investigating the role of Lxr during development.
PMID- 26427654
TI - Influence of organic matters on AsIII oxidation by the microflora of polluted
soils.
AB - The global AsIII-oxidizing activity of microorganisms in eight surface soils from
polluted sites was quantified with and without addition of organic substrates.
The organic substances provided differed by their nature: either yeast extract,
commonly used in microbiological culture media, or a synthetic mixture of defined
organic matters (SMOM) presenting some common features with natural soil organic
matter. Correlations were sought between soil characteristics and both the AsIII
oxidizing rate constants and their evolution in accordance with inputs of organic
substrates. In the absence of added substrate, the global AsIII oxidation rate
constant correlated positively with the concentration of intrinsic organic matter
in the soil, suggesting that AsIII-oxidizing activity was limited by organic
substrate availability in nutrient-poor soils. This limitation was, however,
removed by 0.08 g/L of added organic carbon. In most conditions, the AsIII
oxidation rate constant decreased as organic carbon input increased from 0.08 to
0.4 g/L. Incubations of polluted soils in aerobic conditions, amended or not with
SMOM, resulted in short-term As mobilization in the presence of SMOM and active
microorganisms. In contrast, microbial AsIII oxidation seemed to stabilize As
when no organic substrate was added. Results suggest that microbial speciation of
arsenic driven by nature and concentration of organic matter exerts a major
influence on the fate of this toxic element in surface soils.
PMID- 26427655
TI - Quality assurance in clinical trials--the role of pathology.
AB - In the last two decades, our knowledge about cancer genetics and cancer biology
increased exponentially. Deep sequencing now allows rapid and cost-effective
analysis of entire cancer genomes. Dysregulation of cell growth, cell survival,
tissue homeostasis, and immune surveillance have been recognized as hallmarks of
cancer. In parallel, diagnostic surgical pathology has been harmonized and
consensus diagnostic criteria for cancer classification have been developed by
initiatives of the World Health Organization, the International Agency for
Research on Cancer, and the Union for International Cancer Control.
Pharmaceutical companies developed novel drugs targeting specific molecules in
signaling pathways, which has allowed the development of the concept of precision
medicine. Now, we are facing a large number of clinical trials which bring
together these advances and will explore efficacy of novel treatment regimens.
Assessment of the efficacy of a new drug is often coupled with the simultaneous
assessment of the capacity of tissue-based biomarkers to predict response of
individual patients (companion diagnostics/precision medicine). Patients with
histologically similar tumors might respond differently to the same drug. This
review summarizes the diverse roles played by surgical pathologists involved in
clinical trials, with a special focus on quality assurance of diagnostic,
laboratory, and reporting standards.
PMID- 26427656
TI - Potential role of Th17 cells in the pathogenesis of type 2 autoimmune
pancreatitis.
AB - Th17 cells have been shown to play an important role in the pathogenesis of a
variety of autoimmune diseases. The aim of this study was to investigate the
potential role of Th17 cells in autoimmune pancreatitis (AIP). Quantitative real
time polymerase chain reaction (qRT-PCR) was performed to determine gene
expression of the signature cytokines of Th17 cells IL-17A and IL-21 and of the
Th17 lineage-specific transcription factor retinoic acid receptor-related orphan
receptor C (RORC) in human tissue specimens of AIP, classical chronic
pancreatitis (CP), and normal pancreas (NP). Infiltrating immune cells were
characterized by immunohistochemistry (IHC). Gene expression of IL-17A, IL-21,
and RORC were found to be significantly increased in AIP. Accordingly, the number
of Th17 cells was significantly increased in AIP compared to NP or CP. Both gene
expression analysis and IHC revealed a clear difference between type 1 and 2 AIP.
In the periductal compartment of type 2 AIP, which is characterized by
granulocytic epithelial lesions (GELs), the number of infiltrating Th17 cells and
neutrophilic granulocytes was significantly increased compared to type 1 AIP. Our
data suggest that Th17 cells play a role in the pathogenesis of AIP, in
particular of type 2 AIP. Cross-talk between Th17 cells and neutrophilic
granulocytes mediated via IL-17A may be a potential mechanism by which
neutrophils are recruited to the duct and acinar cells with subsequent
destruction, a process that is pathognomonic for type 2 AIP.
PMID- 26427657
TI - ROBO1 deletion as a novel germline alteration in breast and colorectal cancer
patients.
AB - Despite one third of breast (BC) and colorectal cancer (CRC) cases having a
hereditary component, only a small proportion can be explained by germline
mutations. The aim of this study was to identify potential genomic alterations
related to cancer predisposition. Copy number variations (CNVs) were interrogated
in 113 unrelated cases fulfilling the criteria for hereditary BC/CRC and
presenting non-pathogenic mutations in BRCA1, BRCA2, MLH1, MSH2, TP53, and CHEK2
genes. An identical germline deep intronic deletion of ROBO1 was identified in
three index patients using two microarray platforms (Agilent 4x180K and
Affymetrix CytoScan HD). The ROBO1 deletion was confirmed by quantitative PCR
(qPCR). Six relatives were also evaluated by CytoScan HD Array. Genomic analysis
confirmed a co-segregation of the ROBO1 deletion with the occurrence of cancer in
two families. Direct sequencing revealed no pathogenic ROBO1 point mutations.
Transcriptomic analysis (HTA 2.0, Affymetrix) in two breast carcinomas from a
single patient revealed ROBO1 down-expression with no splicing events near the
intronic deletion. Deeper in silico analysis showed several enhancer regions and
a histone methylation mark in the deleted region. The ROBO1 deletion in a
putative transcriptional regulatory region, its down-expression in tumor samples,
and the results of the co-segregation analysis revealing the presence of the
alteration in affected individuals suggest a pathogenic effect of the ROBO1 in
cancer predisposition.
PMID- 26427658
TI - The effect of bovine rotavirus and its nonstructural protein 4 on ER stress
mediated apoptosis in HeLa and HT-29 cells.
AB - Endoplasmic reticulum (ER) plays important roles in multiple cellular processes
as well as cell survival and apoptosis. Perturbation of ER functions leads to ER
stress and unfolded protein response (UPR). The primary goal of this response is
cell survival, but severe ER stress can trigger apoptosis signaling. In tumor
cells, chronically activated UPR response provides tumor growth. So, apoptosis
induced by the ER stress has been the target for anti-cancer therapy. In this in
vitro study, we examined the apoptotic effect associated with ER stress of bovine
rotavirus and its nonstructural protein 4 (NSP4) alone in two cancer cell lines.
The plasmid pcDNA3.1 encoding NSP4 protein of bovine rotavirus transfected with
lipofectamine 2000 into the HeLa and HT-29 cells for protein production. MTT,
flow cytometry, and Western blot were used to evaluate the cell viability,
apoptosis, and expression level of C/EBP-homologous protein (CHOP) and activated
caspase-4. In parallel, the apoptotic effect of the bovine rotavirus associated
with ER stress in the infected cells was examined too. The cytotoxic and
apoptotic effect of NSP4 protein on the cells were statistically significant
compared to the control groups. However, Western blot showed that the expression
of the NSP4 protein by recombinant plasmid did not lead to high expression of
CHOP and activation of caspase-4. Interestingly, rotavirus not only induced
significant apoptosis but also caused an increase in CHOP expression and caspase
4 activation in the infected cells compared to control. As a result, NSP4 protein
and bovine rotavirus can be considered a potential novel bio-therapeutic strategy
for cancer treatment.
PMID- 26427659
TI - Deregulation of miR-93 and miR-143 in human esophageal cancer.
AB - Esophageal squamous cell carcinoma (ESCC) is the second and third most common
malignancy in Iranian males and females, respectively. Treatment of ESCC is
largely ineffective due to lack of detection at early stages of the disease. In
recent years, miRNA, a small RNA molecule, has drawn much attention to
researchers as a potential biomarker for esophageal cancer. miR-93 and miR-143
are two miRNA molecules reported to be frequently deregulated in various cancers,
including prostate, stomach, cervix, and etc. The purpose of this study was to
investigate the expression levels of these miRNAs and evaluate their diagnostic
and therapeutic potential in esophageal squamous cell carcinoma. In this study,
total RNA was extracted from 30 tumor tissues and 30 nontumor tissues of
esophageal tumor margins, using RNX-plus solution. After validating the quality
and quantity of total RNA, cDNAs of interest were synthesized using microRNA
specific cDNA Synthesis Kit. The expression level of miR-93 and miR-143 was
evaluated using quantitative real-time PCR with miRNA-specific primers. Finally,
the obtained data was analyzed by SPSS ver.20 software and paired t test was
performed to observe the significance of difference between groups. The
expression level of miR-93 was significantly increased and of miR-143 was
significantly decreased in most of the examined tumor tissues, compared to
nontumor tissues. Also, our findings did not detect correlation between mir-93
and mir-143 expressions in regard to stage and grade of the samples. These
findings suggest that the deregulation of these miRNAs may play an important role
in esophageal squamous cell carcinoma. Both miR-93 and miR-143 might be used as
potential biomarkers in esophageal squamous cell carcinoma. However, more studies
with large population of samples are necessary.
PMID- 26427660
TI - Long noncoding RNA PVT1 modulates thyroid cancer cell proliferation by recruiting
EZH2 and regulating thyroid-stimulating hormone receptor (TSHR).
AB - The purposes of this study were to investigate the potential roles of long
noncoding RNA (lncRNA) PVT1 in thyroid cancer cell proliferation and to explore
their possible mechanisms. A total of 84 patients who were diagnosed as having
thyroid cancer (papillary thyroid carcinoma (PTC), follicular thyroid carcinoma
(FTC), and anaplastic thyroid carcinoma (ATC)) in Renji Hospital were enrolled in
this study. Expressions of lncRNA PVT1 in thyroid cancer tissues and cell lines
(IHH-4, FTC-133, and 8505C) were analyzed using RT-polymerase chain reaction
(PCR) and western blotting analysis. The effects of lncRNA PVT1 expression on
thyroid cancer cell proliferation and cell cycle were analyzed using flow
cytometry. Furthermore, the effects of lncRNA expression on thyroid-stimulating
hormone receptor (TSHR) expression and polycomb enhancer of zeste homolog 2
(EZH2) were also analyzed using RNA immunoprecipitation (RIP) assay and chromatin
immunoprecipitation (ChIP) assay, respectively. Compared to the controls, lncRNA
PVT1 was significantly up-regulated in thyroid tissues, as well as in three kinds
of tumor cell lines (P < 0.05). Silenced PVT1 significantly inhibited thyroid
cell line IHH-4, FTC-133, and 8505C cell proliferation and arrested cell cycle at
G0/G1 stage and significantly decreased cyclin D1 and TSHR expressions (P <
0.05). Moreover, lncRNA PVT1 could be enriched by EZH2, and silencing PVT1
resulted in the decreased recruitment of EZH2. This study suggested that lncRNA
PVT1 may contribute to tumorigenesis of thyroid cancer through recruiting EZH2
and regulating TSHR expression.
PMID- 26427662
TI - RETRACTED ARTICLE: Upregulation of miR-20a and miR-10a expression levels act as
potential biomarkers of aggressive progression and poor prognosis in cervical
cancer.
PMID- 26427661
TI - Synthetic Tet-inducible small hairpin RNAs targeting hTERT or Bcl-2 inhibit
malignant phenotypes of bladder cancer T24 and 5637 cells.
AB - Small hairpin RNA (shRNA) can inhibit the malignant phenotypes of tumor cell
through ribonucleic acid interference (RNAi). However, it is hardly to be
regulated and it may induce few phenotypic changes. Here, we build a type of
tetracycline (Tet)-inducible vectors which can achieve regulatable expression of
shRNA in a time-dependent manner by using synthetic biology approach. In order to
prove the effectiveness of this device, we chose hTERT and Bcl-2 as target genes
and test the utility of the device on 5637 and T24 cell lines. The experiments
show that the Tet-inducible small hairpin RNA can effectively suppress their
target genes and generate anti-cancer effects on both 5637 and T24 cell lines.
The device we build not only can inhibit proliferation but also can induce
apoptosis and suppress migration of the bladder cancer cell lines 5637 and T24.
The Tet-inducible small hairpin RNAs may provide a novel strategy for the
treatment of human bladder cancer in the future.
PMID- 26427663
TI - The diagnostic utility of the triple markers Napsin A, TTF-1, and PAX8 in
differentiating between primary and metastatic lung carcinomas.
AB - Napsin A and thyroid transcription factor-1 (TTF-1) are useful biomarkers for
differentiating lung adenocarcinoma from squamous cell carcinoma and also for
differentiating primary lung adenocarcinoma from metastatic lung carcinoma. Pair
boxed 8 (PAX8) can help in distinguishing primary lung carcinoma from metastatic
carcinomas and help to determine the primary sites of metastatic carcinomas.
Immunohistochemistry for Napsin A, TTF-1, and PAX8 were performed on 193 cases of
carcinoma: 50 primary lung carcinoma and 143 carcinomas from other sites. Napsin
A and TTF-1 were positive in 54, 52 % of lung carcinomas cases, respectively.
While in adenocarcinoma cases, their expressions were 86.7 and 83.3 %,
respectively. PAX8 was negative in all lung carcinomas. TTF-1 and PAX8 were
positive in 93.3 and 96.7 % of thyroid carcinoma cases and in 87.5 and 93.8 % of
papillary carcinoma respectively, and both were positive in 100 % of follicular
carcinoma. Napsin A was negative in all thyroid carcinomas. Napsin A and PAX8
were positive in 50 and 93.3 % of renal carcinoma cases and in 81.8 and 100 % of
papillary carcinoma, 38.5 and 92.3 % of clear cell carcinoma, and 16.7 and 83.3 %
of chromophobe carcinoma respectively. TTF-1 was negative in all renal
carcinomas. PAX8 was positive in 80 % of ovarian carcinoma cases; 100 and 60 % of
serous mucinous carcinomas, respectively. It was also positive in 100 % of
endometrial carcinoma. Napsin A and TTF-1 were negative in both ovarian and
endometrial carcinomas. Our data demonstrated that combined use of Napsin A, TTF
1, and PAX8 may help in differentiating between primary lung adenocarcinoma and
metastatic lung carcinomas.
PMID- 26427664
TI - Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer
cells.
AB - The colorectal cancer (CRC) is one leading contributor of cancer-related
mortality worldwide. The search for effective anti-CRC agents is valuable. In the
current study, we showed that icaritin (ICT), an active natural ingredient from
the Chinese plant Epimedium, potently inhibited proliferation and survival of
established (HT-29, HCT-116, DLD-1, and SW-620) and primary (patient-derived) CRC
cells. Significantly, ICT mainly induced necrosis, but not apoptosis, in CRC
cells. The necrosis inhibitor necrostatin-1 attenuated ICT-mediated cytotoxicity
in CRC cells. We showed that ICT treatment in CRC cells induced mitochondrial
permeability transition pore (mPTP) opening, which was evidenced by mitochondrial
membrane potential (MMP) decrease and mitochondrial adenine nucleotide
translocator-1 (ANT-1)-cyclophilin-D (CyPD) association. On the other hand, mPTP
blockers, including sanglifehrin A, cyclosporin A, and bongkrekic acid, as well
as siRNA-mediated knockdown of mPTP component (CyPD or ANT-1), significantly
alleviated ICT-mediated cytotoxicity against CRC cells. We suggested that Jun-N
terminal kinase (JNK) activation by ICT mediated mPTP opening and subsequent CRC
cell necrosis. JNK pharmacological inhibition, dominant negative mutation, or
shRNA downregulation suppressed ICT-induced MMP reduction and subsequent HT-29
cell necrosis. In vivo, oral gavage of ICT dramatically inhibited HT-29 xenograft
growth in nude mice. The in vivo activity by ICT was largely attenuated by co
administration with the mPTP blocker CsA. Collectively, our results showed that
ICT exerts potent inhibitory effect against CRC cells in vitro and in vivo. JNK
dependent mPTP necrosis pathway could be key mechanism responsible for ICT's
actions.
PMID- 26427665
TI - The emerging role of Nemo-like kinase (NLK) in the regulation of cancers.
AB - Nemo-like kinase (NLK) is an evolutionarily conserved mitogen-activated protein
(MAP) kinase-related kinase that is highly expressed in neural tissues and
minimally detected in others. Accumulating evidence demonstrates that NLK exerts
a pivotal role in cell proliferation, migration, invasion, and apoptosis via
regulation of a variety of transcriptional molecules. The results of recent
studies have shown that aberrant expression of NLK is significantly associated
with the initiation and progression of various types of human cancers, as well as
clinicopathologic features and survival rate. NLK is gradually considered as a
potential tumor suppressor or an oncogene depending on the tumor system, and
silencing or upregulating of NLK may provide an effective therapeutic approach
against tumors. In this review, we will make a summary on the comprehensive roles
of NLK in the regulation of various cancers.
PMID- 26427666
TI - XPC (A2920C), XPF (T30028C), TP53 (Arg72Pro), and GSTP1 (Ile105Val) polymorphisms
in prognosis of cutaneous melanoma.
AB - This study aimed to evaluate whether XPC A2920C, XPF T30028C, TP53 Arg72Pro, and
GSTP1 Ile105Val polymorphisms alter outcomes of cutaneous melanoma (CM) patients.
DNA from 237 CM patients seen at the University of Campinas Teaching Hospital
from April 2000 to February 2014 was analyzed by polymerase chain reaction and
restriction fragment length polymorphism assays. The prognostic impact of
genotypes of polymorphisms on progression-free survival (PFS) and overall
survival (OS) of CM patients were examined using the Kaplan-Meier probability
estimates and univariate and multivariate Cox regression analyses. At 60 months
of follow-up, shorter PFS and OS were seen in patients with XPF CC genotype (48.9
vs. 66.7 %, P = 0.002; 77.9 vs. 83.5 %, P = 0.006, respectively) and XPF CC +
TP53 ArgArg (43.6 vs. 65.9 %, P = 0.007; 71.6 vs. 84.8 %, P = 0.006,
respectively) compared with those with remaining genotypes (Kaplan-Meier
estimates). Patients with XPF CC (hazard ratio (HR) 2.45, P = 0.002; HR 3.77, P =
0.005) and XPF CC + TP53 ArgArg (HR 2.67, P = 0.009; HR 4.04, P = 0.03) genotypes
had more chance to present tumor progression in univariate and multivariate
analyses, whereas patients with XPF CC (HR 2.78, P = 0.009) and XPF CC + TP53
ArgArg (HR 3.84, P = 0.01) genotypes were under greater risk of progressing to
death in univariate analysis, compared with those with the remaining genotypes.
The data suggest, for the first time, that inherited abnormalities in DNA repair
pathway related to XPF 30028C and TP53 Arg72Pro polymorphisms act as prognostic
factors for PFS and OS of CM patients.
PMID- 26427667
TI - FGF18 as a potential biomarker in serous and mucinous ovarian tumors.
AB - Fibroblast growth factor 18 (FGF18) has been suggested to play important roles in
promoting progression of ovarian high-grade serous carcinoma. Our aim was to
investigate FGF18 expression in the whole spectrum of serous and mucinous ovarian
tumors, highlighting differences in expression within the adenoma-carcinoma
sequence and differences between type I and type II tumors. We also aimed to test
the prognostic significance of this expression and its relation to microvessel
density (MVD). We evaluated the immunohistochemical expression of FGF18 and CD31
in 103 ovarian tumors and statistically analyzed their association with
clinicopathological variables and patients' outcome. FGF18 score increased
significantly within the adenoma-carcinoma sequence for serous and mucinous
tumors. MVD increased significantly only among serous tumors. FGF18 and MVD
correlated significantly (overall and among serous tumors only) and were
significantly higher in type II than type I tumors. Cox regression models were
built. Independent predictors could not be determined due to multicollinearity
between the predictors. However, the combination of International Federation of
Gynecology and Obstetrics (FIGO) stage, ovarian carcinoma type, and/or FGF18
score achieved the highest predictability of poor prognosis. FGF18 could play a
role within the adenoma-carcinoma sequence in type I tumors and might modulate
angiogenesis among serous tumors. Our findings further augment the differences
between type I and type II tumors. The combination of FIGO stage, ovarian
carcinoma type, and/or FGF18 score could predict poor prognosis among ovarian
carcinoma patients. Our work identifies FGF18 in ovarian neoplasia as a promising
field of research, although evaluation of the performance of the developed models
is still needed.
PMID- 26427668
TI - A patient as a self-manager of their personal data on health and disease with new
technology--challenges for nursing education.
AB - Background: Digital technologies have transformed nearly every aspect of our
lives. However, for many of us, they have not yet improved the way we receive or
participate in our health services and disease care. Hostetter et al. (2014)
explore in a new multimedia essay the changes occurring with the arrival of new
digital tools, from mobile apps and data-driven software solutions to wearable
sensors that transmit information to a patient's team of health care providers.
Digitisation will revolutionise health technology to a new extent, as the self
measurement, cloud services, teleconsultation and robotics technologies are being
used to get health expenditure under control. In the future, robots will dispense
drugs, and treatment routines will utilise cloud services (Biesdorf and
Niedermann, 2014; Grain and Sharper, 2013). According to the rationale of the
Horizon 2020 (European Commission, 2013b) work programme, personalising health
and care has been stated to empower citizens and patients to manage their own
health and disease, which can result in more cost-effective healthcare systems by
enabling the management of chronic diseases outside institutions, improving
health outcomes, and by encouraging healthy citizens to remain so. Solutions
should be developed and tested with the use of open innovation platforms, such as
large-scale demonstrators for health and service innovation. It is a fact that
ICT/new health technology and personal health applications are transforming
patients' self-management in many ways. A huge amount of personal health
application solutions are being offered in the marketplace, which engage in
activities that promote health, monitoring the symptoms and signs of illness, and
managing the impact of illness (European Commission eHealth Action Plan 2012
2020, 2012). The WHO (2011) has conducted a comprehensive study and published a
report on Member States' use of mHealth (mobile Health) as well as the readiness
and barriers to its use. The percentage of countries reporting that they had
formally evaluated mHealth initiatives was 12%. Seven per cent of developing
countries reported conducting a mHealth evaluation. Mobile technologies have
already changed, and they will continue to change the lives of millions around
the world. In the WHO's report, it was estimated that mHealth can revolutionise
health and well-being outcomes if implemented strategically and systematically,
thereby providing virtually anyone with a mobile phone with health and well-being
expertise and knowledge in real-time. In the research reports (European
Commission eHealth Action Plan 2012-2020, 2012; Blake, 2013), it was reported
that mobile phones as a tool are cost-effective and wide reaching, while they
easily target large samples and hard-to-reach groups. Studies show that eHealth
as a way to self-monitor and self-manage as well as supportive interventions for
clients offers a good possibility to bridge the gap between inpatient and
outpatient care. The mobile phone is especially effective in enhancing the
therapist-patient bond so that this does not collapse when the client leaves the
therapist's consulting room. Furthermore, eHealth applications can assist the
client to cope with everyday situations in an autonomous way while improving the
transfer of the abilities acquired by the client in the health care setting to
everyday life. The findings of various projects (European Commission eHealth
Action Plan 2012-2020, 2012; European Commission, 2012; European Commission,
2013b; Hamalainen, 2013) provide an opportunity for an open discussion regarding
the digital health revolution, which will change health care processes and
citizens' applications for health promotion and self-care.
PMID- 26427669
TI - Narrative competence: A neglected area in undergraduate curricula.
PMID- 26427670
TI - Notch2 signaling contributes to cell growth, invasion, and migration in salivary
adenoid cystic carcinoma.
AB - Many studies have explored whether the Notch signaling pathway has a tumor
suppressive or an oncogenic role in various tumors; however, the role of the
Notch signaling pathway in salivary adenoid cystic carcinoma (SACC) is still
unknown. In this study, we attempt to define the role of Notch2 signaling in cell
growth, invasion, and migration in SACC. We compared Notch2 expression in
clinical SACC samples with that of normal samples by using immunohistochemical
staining. Then, we down-regulated Notch2 expression to observe the effect of
Notch2 on proliferation, invasion, migration, and the expression of known target
genes of Notch signal pathway. According to our results, Notch2 expression was
higher in SACC tissues compared with normal tissues. Knockdown of Notch2
inhibited cell proliferation, invasion, and migration in vitro and down-regulated
the expression of HEY2 and CCND1. The results of this study suggest that Notch2
has an essential role in the cell growth, invasion, and migration of SACC. Notch2
may therefore be a potential target gene for the treatment of SACC by interfering
with cell growth and metastasis.
PMID- 26427672
TI - The beta-Barrel Assembly Machinery Complex.
AB - The outer membranes of gram-negative bacteria contain integral membrane proteins,
most of which are of beta-barrel structure, and critical for bacterial survival.
These beta-barrel proteins rely on the beta-barrel assembly machinery (BAM)
complex for their integration into the outer membrane as folded species. The
central and essential subunit of the BAM complex, BamA, is a beta-barrel protein
conserved in all gram-negative bacteria and also found in eukaryotic organelles
derived from bacterial endosymbionts. In Escherichia coli, BamA docks with four
peripheral lipoproteins, BamB, BamC, BamD and BamE, partner subunits that add to
the function of the BAM complex in outer membrane protein biogenesis. By way of
introduction to this volume, we provide an overview of the work that has
illuminated the mechanism by which the BAM complex drives beta-barrel assembly.
The protocols and methodologies associated with these studies as well as the
challenges encountered and their elegant solutions are discussed in subsequent
chapters.
PMID- 26427671
TI - Brain opioid and nociceptin receptors are involved in regulation of bombesin
induced activation of central sympatho-adrenomedullary outflow in the rat.
AB - Previously, we reported that central administration of bombesin, a stress-related
peptide, elevated plasma levels of catecholamines (noradrenaline and adrenaline)
in the rat. The sympatho-adrenomedullary system, which is an important component
of stress responses, can be regulated by the central opioid system. In the
present study, therefore, we examined the roles of brain opioid receptor subtypes
(u, delta, and kappa) and nociceptin receptors, originally identified as opioid
like orphan receptors, in the bombesin-induced activation of central sympatho
adrenomedullary outflow using anesthetized male Wistar rats.
Intracerebroventricularly (i.c.v.) administered bombesin-(1 nmol/animal) induced
elevation of plasma catecholamines was significantly potentiated by pretreatment
with naloxone (300 and 1000 ug/animal, i.c.v.), a non-selective antagonist for u
, delta-, and kappa-opioid receptors. Pretreatment with cyprodime (100 ug/animal,
i.c.v.), a selective antagonist for u-opioid receptors, also potentiated the
bombesin-induced responses. In contrast, pretreatment with naltrindole (100
ug/animal, i.c.v.) or nor-binaltorphimine (100 ug/animal, i.c.v.), a selective
antagonist for delta- or kappa-opioid receptors, significantly reduced the
elevation of bombesin-induced catecholamines. In addition, pretreatment with JTC
801 (30 and 100 ug/animal, i.c.v.) or J-113397 (100 ug/animal, i.c.v.), which are
selective antagonists for nociceptin receptors, also reduced the bombesin-induced
responses. These results suggest that brain u-opioid receptors play a suppressive
role and that brain delta-, kappa-opioid, and nociceptin receptors play a
facilitative role in the bombesin-induced elevation of plasma catecholamines in
the rat. Thus, in the brain, these receptors could play differential roles in
regulating the activation of central sympatho-adrenomedullary outflow.
PMID- 26427673
TI - Yeast Mitochondria as a Model System to Study the Biogenesis of Bacterial beta
Barrel Proteins.
AB - Beta-barrel proteins are found in the outer membrane of Gram-negative bacteria,
mitochondria, and chloroplasts. The evolutionary conservation in the biogenesis
of these proteins allows mitochondria to assemble bacterial beta-barrel proteins
in their functional form. In this chapter, we describe exemplarily how the
capacity of yeast mitochondria to process the trimeric autotransporter YadA can
be used to study the role of bacterial periplasmic chaperones in this process.
PMID- 26427674
TI - Experimental Methods for Studying the BAM Complex in Neisseria meningitidis.
AB - Neisseria meningitidis is a human pathogen. It is intensively studied for host
pathogen interactions and vaccine development. However, its favorable growth
properties, genetic accessibility, and small genome size also make it an
excellent model organism for studying fundamental biological processes, such as
outer membrane biogenesis. Indeed, the first component of the assembly machinery
for outer-membrane proteins, the BAM complex, was identified in N. meningitidis.
Here, we describe protocols to inactivate chromosomal genes and to express genes
from a well-controlled promoter on a plasmid in N. meningitidis. Together, these
protocols can be used, for example, to deplete cells from essential components of
the BAM complex. We also describe a simple, gel-based assay to assess the proper
functioning of the BAM complex in vivo.
PMID- 26427675
TI - Heat Modifiability of Outer Membrane Proteins from Gram-Negative Bacteria.
AB - beta-barrel membrane proteins are somewhat unique in that their folding states
can be monitored using semi-native SDS-PAGE methods to determine if they are
folded properly or not. This property, which is commonly referred to as heat
modifiability, has been used for many years on both purified protein and on whole
cells to monitor folded states of proteins of interest. Additionally, heat
modifiability assays have proven indispensable in studying the BAM complex and
its role in folding and inserting beta-barrel membrane proteins into the outer
membrane. Here, we describe the protocol our lab uses for performing the heat
modifiability assay in our studies on outer membrane proteins.
PMID- 26427676
TI - The Role of a Destabilized Membrane for OMP Insertion.
AB - Here we describe the procedures used in our laboratory for the in vitro
investigation of the apparent folding kinetics as well as the folding
efficiencies of outer membrane proteins (OMPs). Because microbial OMPs display a
change in their gel migration upon folding, the usage of traditional gel
electrophoresis is a standard method of folding analysis. Additional aspects of
the method we detail herein include the preparation and storage of OMP stocks,
the setup procedures for a folding reaction, and the analysis of fraction folded
from scanned gel images.
PMID- 26427677
TI - Treponema pallidum in Gel Microdroplets: A Method for Topological Analysis of
BamA (TP0326) and Localization of Rare Outer Membrane Proteins.
AB - The noncultivable spirochete Treponema pallidum subspecies pallidum (T. pallidum)
is the etiological agent of venereal syphilis. In contrast to the outer membranes
(OMs) of gram-negative bacteria, the OM of T. pallidum lacks lipopolysaccharide,
contains a paucity of integral membrane proteins, and is extremely labile. The
lability of the T. pallidum OM greatly hinders efforts to localize the
bacterium's rare outer membrane proteins (OMPs). To circumvent this problem, we
developed the gel microdroplet method in which treponemes are encapsulated in
porous agarose beads and then probed with specific antibodies in the absence or
presence of low concentrations of the non-ionic detergent Triton X-100. To
demonstrate the general utility of this method for surface localization of any T.
pallidum antigen, herein we describe a protocol for immunolabeling of
encapsulated treponemes using antibodies directed against the beta-barrel and
POTRA domains of TP0326, the spirochete's BamA ortholog.
PMID- 26427678
TI - Analyzing the Role of Periplasmic Folding Factors in the Biogenesis of OMPs and
Members of the Type V Secretion System.
AB - The outer membrane (OM) of gram-negative bacteria is highly packed with OM
proteins (OMPs) and the trafficking and assembly of OMPs in gram-negative
bacteria is a subject of intense research. Structurally, OMPs vary in the number
of beta-strands and in the size and complexity of extra-membrane domains, with
extreme examples being the members of the type V protein secretion system (T5SS),
such as the autotransporter (AT) and intimin/invasin families of secreted
proteins, in which a large extracellular "passenger" domain is linked to a beta
barrel that inserts in the OM. Despite their structural and functional diversity,
OMPs interact in the periplasm with a relatively small set of protein chaperones
that facilitate their transport from the inner membrane (IM) to the beta-barrel
assembly machinery (BAM complex), preventing aggregation and assisting their
folding in various aspects including disulfide bond formation. This chapter is
focused on the periplasmic folding factors involved in the biogenesis of integral
OMPs and members of T5SS in E. coli, which are used as a model system in this
field. Background information on these periplasmic folding factors is provided
along with genetic methods to generate conditional mutants that deplete these
factors from E. coli and biochemical methods to analyze the folding, surface
display, disulfide formation and oligomerization state of OMPs/T5SS in these
mutants.
PMID- 26427679
TI - An In Vitro Assay for Substrate Translocation by FhaC in Liposomes.
AB - The two-partner secretion (TPS) pathway is used by gram-negative bacteria to
secrete a large family of virulence exoproteins. Its name is derived from the
fact that it involves two proteins, a secreted TpsA protein and a cognate TpsB
transporter in the outer membrane. A typical TPS system is represented by the
filamentous hemagglutinin FhaB (TpsA protein) and its transporter FhaC (TpsB
protein) of Bordetella pertussis. Results from mutational analysis and
heterologous expression experiments suggested that FhaC is essential for FhaB
translocation across the outer membrane of bacteria. We have devised a cell-free
biochemical assay to reconstitute in vitro the translocation of FhaB into
reconstituted membrane vesicles. Thereby the clearest evidence has been provided
that the single beta-barrel FhaC protein serves as the sole translocator to
transport FhaB across the outer membrane. This is the first in vitro assay for
protein secretion across the Escherichia coli outer membrane and the detailed
protocol described here should be amenable to modifications and application to
the analysis of related protein transport events occurring at the outer membranes
of gram-negative bacteria.
PMID- 26427680
TI - Measuring Cell-Cell Binding Using Flow-Cytometry.
AB - Cell-cell adhesion mediates a number of competitive and cooperative microbial
interactions. Fluorescence labeling and flow cytometry techniques allow us to
observe and measure these interactions rapidly and easily. Here, we describe a
method to quantify cell-cell adhesion events between two differentially labeled
cell populations.
PMID- 26427681
TI - Methods to Characterize Folding and Function of BamA Cross-Link Mutants.
AB - The utility of protein engineering, both the mutation and deletion of specific
amino acids, to investigate protein structure and function has been demonstrated
time and time again, and intermolecular and intramolecular interactions within
the BAM complex and its individual components are no exception. Extensive efforts
have probed conserved and unique amino acid sequences of the Bam proteins to
define their functional roles. This chapter summarizes efforts as applied to the
disulfide cross-link mutants of BamA and describes experimental methods used in
our studies to determine that lateral opening of the barrel domain is required
for function.
PMID- 26427682
TI - Small Angle X-ray Scattering (SAXS) Characterization of the POTRA Domains of
BamA.
AB - BamA is the central component of the BAM complex and contains a C-terminal beta
barrel domain embedded in the outer membrane, and a soluble, periplasmic domain,
made out of five polypeptide transport associated (POTRA) motifs. Structural
characterization of the POTRA domains was carried out by a combination of
crystallographic, NMR and solution Small Angle X-ray Scattering (SAXS)
approaches. Despite its limited resolution, SAXS is an excellent complement to
NMR and crystallography. It is well suited to validate high-resolution models in
solution and is particularly useful to characterize flexible systems such as the
POTRA domains of BamA. Here we present a protocol for sample preparation and
discuss the considerations of SAXS data collection and quality control, which is
applicable to most soluble proteins.
PMID- 26427683
TI - Assessing the Outer Membrane Insertion and Folding of Multimeric Transmembrane
beta-Barrel Proteins.
AB - In addition to the cytoplasmic membrane, Gram-negative bacteria have a second
lipid bilayer, the outer membrane, which is the de facto barrier between the cell
and the extracellular milieu. Virtually all integral proteins of the outer
membrane form beta-barrels, which are inserted into the outer membrane by the BAM
complex. Some outer membrane proteins, like the porins and trimeric
autotransporter adhesins, are multimeric. In the former case, the porin trimer
consists of three individual beta-barrels, whereas in the latter, the single
autotransporter beta-barrel domain is formed by three separate polypeptides. This
chapter reviews methods to investigate the folding and membrane insertion of
multimeric OMPs and further explains the use of a BamA depletion strain to study
the effects of the BAM complex on multimeric OMPs in E. coli.
PMID- 26427684
TI - The Expression, Purification, and Structure Determination of BamA from E. coli.
AB - In gram-negative bacteria, assembly of outer membrane proteins requires the
multicomponent beta-barrel assembly machinery (BAM) complex, of which BamA is an
essential and evolutionarily conserved integral outer membrane protein. To
understand how BamA facilitates outer membrane protein biogenesis, it is
important to obtain sufficient amounts of purified recombinant BamA protein for
in vitro functional analysis and structure determination. In this chapter, we
describe the protocol that we used in our laboratory for the cloning, expression,
and purification of E. coli BamA and its N-terminal deletion variants for in
vitro functional studies and for structure determination of the beta-barrel
domain alone (residues 426-810).
PMID- 26427685
TI - Expression and Purification of the Individual Bam Components BamB-E.
AB - BamB, BamC, BamD, and BamE are lipoproteins that, along with the integral
membrane protein BamA, form the beta-barrel assembly machinery (BAM) complex in
the outer-membrane of Gram-negative bacteria. Elucidating the roles that these
lipoproteins play in the beta-barrel assembly process requires both structural
and functional studies that rely on milligram quantities of pure protein. Here,
we describe a simple protocol for expressing individual BamB-BamE proteins in
Escherichia coli and purifying them by nickel affinity and size-exclusion
chromatography. This protocol yields pure proteins in amounts that are sufficient
for crystallization trials, in vitro protein-protein interaction studies, NMR,
and other biochemical experiments.
PMID- 26427686
TI - Structure Determination of the BAM Complex Accessory Lipoproteins BamB-E.
AB - Outer membrane protein biogenesis is a fundamental and essential process in all
Gram-negative bacteria. The key players conducting this process are organized in
the beta-barrel assembly machinery (BAM) complex. This complex has recently
attracted a lot of attention due to its importance in cell wall generation,
maintenance, and the fascinating yet partially unknown mechanism. The currently
best studied example is the BAM complex from E. coli which comprises five
proteins, BamA-BamE, two of which, BamA and BamD, are essential for cell
survival. Four of the complex proteins, BamB-BamE, are lipoproteins and are
attached to the outer membrane via N-terminal lipid anchors. Two of them, BamB
and BamD, comprise protein folds known to mediate protein-protein interactions
through WD40 and TPR domains, respectively. Structures of BamB to BamE have been
determined using X-ray crystallography, NMR and SAXS techniques. Details on
protein preparation, crystallization, data acquisition, and determination of
structures are given here along with the brief summary of the currently available
structural Bam protein repertoire.
PMID- 26427687
TI - An In Vitro Assay for Outer Membrane Protein Assembly by the BAM Complex.
AB - To elucidate the mechanism of a biochemical process it is often essential to
reconstitute the reaction in vitro using the minimal set of factors required to
drive the reaction to completion. Here, we describe a method to reconstitute the
folding and membrane integration of bacterial outer membrane (OM) proteins that
have a characteristic beta-barrel structure. In this method the BAM complex, a
heteroligomer that catalyzes the membrane integration of beta-barrel proteins, is
first purified and inserted into small lipid vesicles. Denatured OM proteins are
then assembled and integrated into the vesicles in the presence of a molecular
chaperone called SurA.
PMID- 26427688
TI - Identification of BamC on the Surface of E. coli.
AB - In order to relate the structural architecture of the BAM complex to its function
in outer membrane protein assembly, the arrangement of each component within the
complex is vital. This chapter explores the structure and topology of BamC, using
a range of biochemical techniques to probe the topology and surface exposure.
PMID- 26427689
TI - Construction and Characterization of an E. coli bamD Depletion Strain.
AB - The central Bam components BamA and BamD are both essential genes in E. coli, a
fact that often confounds genetic analysis using classical methods. The isolation
of "depletion strains" in which these genes can be conditionally expressed
removes this obstacle and facilitates the in vivo characterization of Bam
function. This chapter describes an efficient two-step recombineering method for
the construction of such a depletion strain, which contains an arabinose
inducible allele of bamD, using the lambda Red system. Additionally, a simple
protocol is presented for the depletion of bamD expression in live cells, which
is particularly useful for the characterization of mutant alleles of bamD
(complementation analysis). In principle, the procedures described can be adapted
to produce and characterize depletion strains for any essential gene in E. coli
or any other bacterium that is similarly amenable to genome engineering.
PMID- 26427690
TI - Expression, Purification, and Screening of BamE, a Component of the BAM Complex,
for Structural Characterization.
AB - In Gram-negative bacteria, integral outer membrane beta-barrel proteins (OMP) are
assembled by the beta-barrel assembly machine complex, or BAM complex. This
complex includes the essential components BamA, an OMP composed of a carboxyl
terminal beta-barrel domain and five polypeptide transport-associated domains
(POTRA), and the lipoprotein BamD. In Escherichia coli, the complex contains an
additional three lipoproteins, BamB, C and E required for efficient delivery of
OMPs to the outer membrane. Here we provide methods for production, isotope
labeling, purification, and functional screening of BamE for research purposes.
Purification strategies of both the soluble and wild-type membrane-tethered forms
of BamE are described using techniques including osmotic shock, Ni-NTA
purification, and size-exclusion chromatography. Functional screening using a
simple plate assay is also described which allows screening for defects in outer
membrane permeability.
PMID- 26427691
TI - Purification and Bicelle Crystallization for Structure Determination of the E.
coli Outer Membrane Protein TamA.
AB - TamA is an Omp85 protein involved in autotransporter assembly in the outer
membrane of Escherichia coli. It comprises a C-terminal 16-stranded transmembrane
beta-barrel as well as three periplasmic POTRA domains, and is a challenging
target for structure determination. Here, we present a method for crystal
structure determination of TamA, including recombinant expression in E. coli,
detergent extraction, chromatographic purification, and bicelle crystallization
in combination with seeding. As a result, crystals in space group P21212 are
obtained, which diffract to 2.3 A resolution. This protocol also serves as a
template for structure determination of other outer membrane proteins, in
particular of the Omp85 family.
PMID- 26427692
TI - Strategies for the Analysis of Bam Recognition Motifs in Outer Membrane Proteins.
AB - Well-structured proteins interact with other proteins through surface-surface
interactions. In such cases, the residues that form the interacting surface are
not necessarily neighboring residues on the level of protein sequence. In
contrast, unfolded or partially unfolded proteins can interact with other
proteins through defined linear motifs. In the case of the beta-barrel assembly
machinery (BAM) in the outer membrane of Gram-negative bacteria, unfolded beta
barrel proteins are recognized through a C-terminal linear motif, and are
inserted into the membrane. While the exact mechanism of recognition is still
under investigation, it has been shown that mutations in the recognition motif
can partially or completely abolish membrane insertion. In this chapter, we
demonstrate the workflow for motif discovery, motif extraction, and motif
visualization on the example of the C-terminal motifs in transmembrane beta
barrel proteins.
PMID- 26427693
TI - Summary and Future Directions.
AB - beta-barrel outer membrane proteins (OMPs) are found in the outer membranes (OMs)
of all gram-negative bacteria, yet exactly how they are folded and inserted
remains unknown. The last decade has provided a wealth of discovery including the
identification of the BAM complex, a multicomponent complex responsible for the
biogenesis of all OMPs into the OM. It is anticipated that the next decade will
further advance our knowledge of how the BAM complex is able to perform its
unique and interesting function.
PMID- 26427694
TI - Evaluation of positive surgical margins in patients undergoing robot-assisted and
open radical prostatectomy according to preoperative risk groups.
AB - OBJECTIVES: Recent studies showed that robot-assisted radical prostatectomy
(RARP) represents an oncologically safe procedure in patients with prostate
cancer (PCa), where the rate of positive surgical margins (PSMs) might be lower
in patients treated with RARP as compared with that of those undergoing the open
approach (open RP [ORP]). The aim of this study is to analyze the rate of PSMs
according to preoperative risk groups in a large cohort of patients treated with
RARP and ORP in a single institution with standardized surgical technique and
pathological examination. MATERIALS AND METHODS: We evaluated 6,194 consecutive
patients with PCa undergoing either ORP (71.1%) or RARP (28.9%) between 1992 and
2014. Logistic regression analyses were used to test the association between type
of surgery and PSMs in each preoperative risk group (low vs. intermediate vs.
high) after adjusting for confounders. RESULTS: Overall, 21.6% patients had PSMs.
RARP was associated with a lower rate of PSMs in low-risk (11.5 vs. 15.4%, P =
0.01), intermediate-risk (18.9 vs. 23.5%, P = 0.008), and high-risk patients
(19.7 vs. 30.1%, P<0.001). In multivariable analyses, after stratification
according to risk group categories, no difference in PSMs between RARP and ORP
was observed for low-risk (odds ratio [OR] = 0.87, P = 0.46) and intermediate
risk patients (OR = 0.84, P = 0.19). Conversely, RARP was associated with lower
odds of PSMs in high-risk patients (OR = 0.69, P = 0.04). Similar results were
observed when our analyses were repeated after accounting for pathological
characteristics, in patients treated between 2006 and 2014 and in a cohort of men
treated by high-volume surgeons (all P<= 0.03). CONCLUSIONS: The introduction of
RARP at our institution led to a significant reduction in the risk of PSMs in
patients with PCa with high-risk disease.
PMID- 26427695
TI - Unemployment risk and income change after testicular cancer diagnosis: A
population-based study.
AB - BACKGROUND: Among patients with cancer, returning to full working may serve as an
indicator for return to normal lifestyle following illness, as opposed to
unemployment or shifting to part-time work. The aim of the project was to clarify
the association between unemployment risk and decreased income at 4 years after
the diagnosis of testicular cancer (TC). PARTICIPANTS AND METHODS: A case control
in a cohort study includes baseline measurement of people participating in the
Israeli Central Bureau of Statistics 1995 National Census, and follow-up until
2011. Cancer incidence, employment status, and income level were ascertained
through the Israel Cancer Registry and Tax Authority, respectively. A matched
group was sampled from the population in the census. Binary logistic regression
analyses were used to assess odds ratios (ORs) for study's outcomes, while
controlling for age, ethnicity, education, and socioeconomic and employment
status at 2 years before diagnosis. RESULTS: A total of 113 cases of TC and 468
persons in the matched group were included in the study after excluding persons
who died during the study period. No association was found between TC and
subsequent risk after the 4 years of unemployment (OR = 1.12, 95% CI: 0.65-1.95)
or decreased income (OR = 1.41, 95% CI: 0.84-2.36). Predictors of subsequent
unemployment were unemployment 2 years before diagnosis (OR = 6.91, 95% CI: 4.39
10.86) and increasing age (OR = 1.03 per year, 95% CI: 1.01-1.06). CONCLUSION: TC
survivorship is not associated with subsequent unemployment or decreased income
at 4 years after diagnosis.
PMID- 26427696
TI - Contemporary role of advanced imaging for bladder cancer staging.
AB - Optimized pretreatment staging of bladder urothelial carcinoma is essential in
guiding appropriate treatment. This staging process relies heavily on tissue
pathology from transurethral resection of bladder tumor as well as imaging for
diagnosis of local, regional, nodal, or distant visceral spread. Accurate
preoperative staging is critical for appropriate treatment decision making and
patient counseling as these are based on the extent of disease involvement,
largely classifying the cancer as having local, regional, or distant spread.
Currently, the gold standard of transurethral resection of bladder tumor followed
by computed tomography imaging with intravenous contrast provides excellent
staging specificity in cases of more advanced bladder cancers with suspicion of
spread; however, this often under stages patients that can lead to adverse
oncologic outcomes in these patients undergoing radical cystectomy. Incorporation
of novel imaging modalities including multiparametric magnetic resonance imaging
and positron emission tomography imaging have shown promise in improving accuracy
of staging for both local and distant disease in patients with bladder urothelial
carcinoma.
PMID- 26427697
TI - The value of a rapid contrast-enhanced angio-MRI protocol in the detection of
head and neck paragangliomas in SDHx mutations carriers: a retrospective study on
behalf of the PGL.EVA investigators.
AB - OBJECTIVES: To assess the performance of a simplified MRI protocol consisting of
a contrast-enhanced three-dimensional MR angiography (CE-MRA) in association with
a post-contrast T1-weighted sequence (T1WIV) for the detection of HNPGLs in SDHx
mutation carriers. METHODS: This retrospective sub-study is based on the
multicenter PGL.EVA cohort, which prospectively enrolled SDHx mutation carriers
from 2005 to 2009; 157 index cases or relatives were included. CE-MRA and the
T1WIV images were read solely with knowledge of the clinical data but blind to
the diagnosis. Sensitivity, specificity and likelihood ratios for the simplified
MRI protocol were compared to the full MRI protocol reading results and to the
gold standard status obtained through the consensus of an expert committee.
RESULTS: The sensitivity and specificity of the readings of the simplified MRI
protocol were, respectively, 88.7 % (95 % CI = 78.1-95.3) and 93.7 % (95 % CI =
86.8-97.7) versus 80.7 % (95 % CI = 68.6-89.6) and 94.7 % (95 % CI = 88.1-98.3)
for the readings of the full MRI protocol. CONCLUSIONS: The simplified post
contrast MRI with shorter duration (5 to 10 minutes) showed no performance
difference compared to the lengthy standard full MRI and can be proposed for the
detection of head and neck paragangliomas (HNPGLs) in SDHx mutation carriers. KEY
POINTS: * Rapid angio-MRI protocol and the usual lengthy protocol show equal
diagnostic performance. * The CE-MRA is the key sequence for the detection of
HNPGLs. * The T1WIV sequence assists in localizing HNPGLs.
PMID- 26427698
TI - Diffusion-weighted magnetic resonance imaging of thymoma: ability of the Apparent
Diffusion Coefficient in predicting the World Health Organization (WHO)
classification and the Masaoka-Koga staging system and its prognostic
significance on disease-free survival.
AB - OBJECTIVES: To evaluate the usefulness of diffusion-weighted magnetic resonance
for distinguishing thymomas according to WHO and Masaoka-Koga classifications and
in predicting disease-free survival (DFS) by using the apparent diffusion
coefficient (ADC). METHODS: Forty-one patients were grouped based on WHO (low
risk vs. high-risk) and Masaoka-Koga (early vs. advanced) classifications. For
prognosis, seven patients with recurrence at follow-up were grouped separately
from healthy subjects. Differences on ADC levels between groups were tested using
Student-t testing. Logistic regression models and areas under the ROC curve
(AUROC) were estimated. RESULTS: Mean ADC values were different between groups of
WHO (low-risk = 1.58 +/- 0.20 * 10(-3)mm(2)/sec; high-risk = 1.21 +/- 0.23 * 10(
3)mm(2)/sec; p < 0.0001) and Masaoka-Koga (early = 1.43 +/- 0.26 * 10(
3)mm(2)/sec; advanced = 1.31 +/- 0.31 * 10(-3)mm(2)/sec; p = 0.016)
classifications. Mean ADC of type-B3 (1.05 +/- 0.17 * 10(-3)mm(2)/sec) was lower
than type-B2 (1.32 +/- 0.20 * 10(-3)mm(2)/sec; p = 0.023). AUROC in
discriminating groups was 0.864 for WHO classification (cut-point = 1.309 * 10(
3)mm(2)/sec; accuracy = 78.1 %) and 0.730 for Masaoka-Koga classification (cut
point = 1.243 * 10(-3)mm(2)/sec; accuracy = 73.2 %). Logistic regression models
and two-way ANOVA were significant for WHO classification (odds ratio[OR] = 0.93,
p = 0.007; p < 0.001), but not for Masaoka-Koga classification (OR = 0.98, p =
0.31; p = 0.38). ADC levels were significantly associated with DFS recurrence
rate being higher for patients with ADC <= 1.299 * 10(-3)mm(2)/sec (p = 0.001;
AUROC, 0.834; accuracy = 78.0 %). CONCLUSIONS: ADC helps to differentiate high
risk from low-risk thymomas and discriminates the more aggressive type-B3.
Primary tumour ADC is a prognostic indicator of recurrence. KEY POINTS: * DW-MRI
is useful in characterizing thymomas and in predicting disease-free survival. *
ADC can differentiate low-risk from high-risk thymomas based on different
histological composition * The cutoff-ADC-value of 1.309 * 10 (-3) mm (2) /sec is
proposed as optimal cut-point for this differentiation * The ADC ability in
predicting Masaoka-Koga stage is uncertain and needs further validations * ADC
has prognostic value on disease-free survival and helps in stratification of
risk.
PMID- 26427699
TI - Safety and Clinical Effectiveness of Percutaneous Vertebroplasty in the Elderly
(>=80 years).
AB - PURPOSE: To evaluate the safety and clinical effectiveness of percutaneous
vertebroplasty (PVP) in patients aged 80 and over. METHODS: One hundred and
seventy-three patients (127 women, 46 men; mean age = 84.2y) underwent 201 PVP
procedures (391 vertebrae) in our institution from June 2008 to March 2012. One
hundred and twenty-six patients (73 %) had osteoporotic vertebral compression
fractures (VCF), 36 (20.5 %) were treated for tumour lesions, and the remaining
11 (6.5 %) for lesions from another cause. Comorbidities and American Society of
Anesthesiologists (ASA) scores were assessed before treatment. Periprocedural and
delayed complications were systematically recorded. A qualitative scale was used
to evaluate pain relief at 1-month follow-up, ranging from significant pain
worsening to marked improvement or disappearance. New fracture occurrence was
assessed on follow-up imaging. RESULTS: Forty-five percent of patients had
pretreatment ASA class scores >=3. No major complication occurred. Pain was
unchanged in 16.9 % of cases, mildly improved in 31.5 %, and disappeared in 47.8
%. We identified 27 (11 %) symptomatic new VCFs in patients with osteoporosis on
follow-up imaging. The mean delay in diagnosis of new fractures was 5 +/- 8.7
months. CONCLUSIONS: Even in the elderly, PVP remains a safe and effective
technique for pain relief, independently of the underlying disease. KEY POINTS: *
Post-PVP pain improvement was observed in 79.3 % of elderly patients. * PVP
remains a safe technique in elderly patients. * No decompensation of comorbidity
was observed in our series.
PMID- 26427700
TI - Protective effect against repeat adverse reactions to iodinated contrast medium:
Premedication vs. changing the contrast medium.
AB - OBJECTIVES: The purpose of this study was to assess the protective effect of
premedication and changing contrast media (CM) against repeat adverse reactions
(ARs) to iodinated CM. METHODS: Between January 2006 and September 2014, 771
cases with previous ARs to CM were administered CM. The same CM that had caused
ARs previously was administered to 491 cases (220 without premedication [defined
as the control group], and 271 with premedication [the premedication alone
group]). A different CM from the previous CM was given to 280 cases (58 without
premedication [the changing CM alone group], and 222 with premedication [the
premedication and changing CM group]). RESULTS: The control group had 61 repeat
ARs (27.7%). The premedication alone group had 47 ARs (17.3%, p<0.01). The
changing CM alone group had 3 ARs (5.2%, p<0.001). Three ARs (7.9%) were observed
in 38 cases changing from one to another low-osmolar nonionic CM. Twenty cases
with previous ARs to the high-osmolar CM and to the low-osmolar ionic CM showed
no ARs. The premedication and changing CM group had 6 ARs (2.7%, p<0.001).
CONCLUSION: Premedication prior to contrast for patients with previous ARs may be
protective, however, changing CM was more effective. KEY POINTS: * In patients
with previous adverse reactions, changing contrast media is recommended. *
Premedication is unnecessary against previous reactions to high-osmolar or ionic
CM. * Changing from one to another low-osmolar non-ionic CM may be effective.
PMID- 26427702
TI - Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition.
AB - Adenomyosis is a heterogenous gynecologic condition. Patients with adenomyosis
can have a range of clinical presentations. The most common presentation of
adenomyosis is heavy menstrual bleeding and dysmenorrhea; however, patients can
also be asymptomatic. Currently, there are no standard diagnostic imaging
criteria, and choosing the optimal treatment for patients is challenging. Women
with adenomyosis often have other associated gynecologic conditions such as
endometriosis or leiomyomas, therefore making the diagnosis and evaluating
response to treatment challenging. The objective of this review was to highlight
current clinical information regarding the epidemiology, risk factors,
pathogenesis, clinical manifestations, diagnosis, imaging findings, and treatment
of adenomyosis. Several studies support the theory that adenomyosis results from
invasion of the endometrium into the myometrium, causing alterations in the
junctional zone. These changes are commonly seen on imaging studies such as
transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). The second
most common theory is that adenomyosis results from embryologic-misplaced
pluripotent mullerian remnants. Traditionally, adenomyosis was only diagnosed
after hysterectomy; however, studies have shown that a diagnosis can be made with
biopsies at hysteroscopy and laparoscopy. Noninvasive imaging can be used to help
guide the differential diagnosis. The most common findings on 2-dimensional/3
dimensional TVUS and MRI are reviewed. Two-dimensional TVUS and MRI have a
respectable sensitivity and specificity; however, recent studies indicate that 3
dimensional TVUS is superior to 2-dimensional TVUS for the diagnosis of
adenomyosis and may allow for the diagnosis of early-stage disease. Management
options for adenomyosis, both medical and surgical, are reviewed. Currently, the
only definitive management option for patients is hysterectomy.
PMID- 26427701
TI - Cholangiocarcinoma: from molecular biology to treatment.
AB - Cholangiocarcinoma is a rare tumor originating in the bile ducts, which,
according to their anatomical location, is classified as intrahepatic,
extrahepatic and hilar. Nevertheless, incidence rates have increased markedly in
recent decades. With respect to tumor biology, several genetic alterations
correlated with resistance to chemotherapy and radiotherapy have been identified.
Here, we highlight changes in KRAS and TP53 genes that are normally associated
with a more aggressive phenotype. Also IL-6 and some proteins of the BCL-2 family
appear to be involved in the resistance that the cholangiocarcinoma presents
toward conventional therapies. With regard to diagnosis, tumor markers most
commonly used are CEA and CA 19-9, and although its use isolated appears
controversial, their combined value has been increasingly advocated. In imaging
terms, various methods are needed, such as abdominal ultrasound, computed
tomography and cholangiopancreatography. Regarding therapy, surgical modalities
are the only ones that offer chance of cure; however, due to late diagnosis, most
patients cannot take advantage of them. Thus, the majority of patients are
directed to other therapeutic modalities like chemotherapy, which, in this
context, assumes a purely palliative role. Thus, it becomes urgent to investigate
new therapeutic options for this highly aggressive type of tumor.
PMID- 26427703
TI - Impact of Laparoscopic Surgical Management of Deep Endometriosis on Pregnancy
Rate.
AB - STUDY OBJECTIVE: To evaluate the impact of laparoscopic excision of lesions on
deep endometriosis-related infertility. DESIGN: Retrospective study. SETTING:
Endometriosis tertiary referral center (Canadian Task Force II-2). PATIENTS: A
group of 115 patients who had undergone laparoscopic surgery for infertility with
histologic confirmation of deep endometriosis. INTERVENTIONS: Patient medical
records and operative reports were reviewed. Telephone interviews were conducted
for long-term follow-up of fertility outcomes. MEASUREMENTS AND MAIN RESULTS:
Evaluation of fertility outcome after laparoscopic treatment of deep
endometriosis by spontaneous conception and by assisted reproductive technology
(ART) correlated with lesion number, size, and location (anterior,
posterolateral, pouch of Douglas, and multiple locations). After a mean follow-up
of 22 months the overall pregnancy rate was 54.78% (n = 63) with a live-birth
rate of 42.6% (n = 49). Among those patients given the chance to conceive
spontaneously (n = 70), the overall pregnancy rate was 60% (n = 42): 38.5% (n =
27) spontaneously and 21.4% (n = 15) by ART. The removal of multiple lesions was
associated with a higher pregnancy rate after surgery. When comparing isolated
lesion size and disease location, there was no difference in pregnancy rate.
Furthermore, those patients who underwent surgical eradication of the disease for
the first time had a higher pregnancy rate (odds ratio, 4.18). CONCLUSION: This
study demonstrates that laparoscopic excision of deep endometriosis enhances
pregnancy rate, by both spontaneous conception and ART. First surgical treatment
of multiple lesions was associated with higher pregnancy rates, whereas isolated
lesions influenced the pregnancy rate irrespective of their location and size.
PMID- 26427704
TI - Efficient passage of human pluripotent stem cells on spider silk matrices under
xeno-free conditions.
AB - Human pluripotent stem cells (hPSCs) hold great promise for applications in
regenerative medicine and pharmaceutical development. Such applications require
cell culture methods and reagents that are chemically defined, xeno-free,
scalable, and low-cost. Herein, we describe non-mechanical passaging of hPSCs on
spider silk films under chemically defined and xeno-free conditions. The cells
were dissociated into single cells or small aggregates using Accutase or enzyme
free dissociation buffer and then passaged to spider silk films, where they
expanded in monolayers until they covered the surface. Cells cultured over 10
passages on spider silk film remained karyotypically normal and pluripotent. In
conclusion, a novel method for passaging dissociated hPSCs under conditions that
are compatible with clinical applications is presented. The method is cost
efficient and may be useful for both research and clinical applications.
PMID- 26427705
TI - One-day front-loading with four doses of rabeprazole followed by a standard twice
daily regimen provides sufficient acid inhibition in extensive metabolizers of
CYP2C19.
AB - BACKGROUND: Four times daily dosing (qid) with a proton pump inhibitor can cause
rapid increase in intragastric pH. We investigated the efficacy of the front
loading with rabeprazole 10 mg qid on a subsequent regimen with rabeprazole 10 mg
twice daily (bid) for 7 days in extensive metabolizers (EMs) of CYP2C19. METHODS:
Five EMs received three different 1-week regimens in a crossover manner as
follows: (1) rabeprazole 10 mg bid for 7 days; (2) a front-loading regimen of
rabeprazole (rabeprazole 10 mg qid on day 0 and bid on days 1 to 7); and (3)
rabeprazole 10 mg qid for 7 days. Five intermediate metabolizers (IMs) and four
poor metabolizers (PMs) received rabeprazole 10 mg bid regimen only. Twenty-four
hour intragastric pH-monitorings were performed on days 1, 4, and 7. Area under
the intragastric pH-time curves (AUCs) from days 1 to 7 was calculated using 24-h
median intragastric pHs on days 1, 4, and 7. RESULTS: Twenty-four-hour
intragastric pHs in the front-loading group on days 1, 4, and 7 were 5.1, 4.9,
and 5.1, respectively. The median AUC with front-loading in EMs (34.4, pH.day)
was significantly higher than that in EMs with rabeprazole 10 mg bid (30.74, p =
0.043). No statistically significant differences in median AUCs were noted among
front-loading in EMs, rabeprazole 10 mg qid in EMs (37.2), rabeprazole 10 mg bid
in IMs (37.3), and PMs (39.4). CONCLUSIONS: The one-day front-loading regimen of
rabeprazole 10 mg qid provided sufficient acid inhibition for 7 days, even in
CYP2C19 EMs.
PMID- 26427706
TI - Luteolin induces caspase-14-mediated terminal differentiation in human epidermal
keratinocytes.
AB - Recent studies have demonstrated the role of caspase-14 in terminally
differentiated keratinocytes, and its expression may decrease the magnitude of
tumors in the epidermis. In the present study, we assessed the potential of
luteolin (LUT) to elicit the expression of caspase-14 in terminal differentiation
of human keratinocytes. The semi-qualitative RT-PCR data revealed a significant
level of caspase-14 expression in LUT-treated human immortalized keratinocytes
(HaCaT) with respect to untreated cells. The quantitative data (ELISA) further
supported the potency of LUT to induce caspase-14 expression at 3.19 ng/ml when
compared to 1.29 ng/ml of vitamin D3 (positive control). Further, the enhanced
expression of human involucrin gene in LUT-treated HaCaT cells confirmed its
ability to drive terminal differentiation in these cells. These preliminary
results provide first-hand information about the in vitro potential of LUT to
elicit the expression of caspase-14, thereby inducing terminal differentiation in
human keratinocytes.
PMID- 26427707
TI - Erratum to: Maintenance of bladder urothelia integrity and successful
urothelialization of various tissue-engineered mesenchymes in vitro.
PMID- 26427708
TI - The primary culture of carp (Cyprinus carpio) macrophages and the verification of
its phagocytosis activity.
AB - This study establishes the primary culture method for red carp (Cyprinus carpio)
macrophages in vitro and lays the foundation for further research in the fish
immune system. The healthy adult red carp was chosen, and mechanical separation
and cell adherent culture methods were used to isolate the primary macrophages.
Compared to the traditional method of Percoll discontinuous density gradient
isolation, the protocol we reported here makes cell isolation steps more concise
and obtains more healthy cells with high macrophage purity. The cells were
uniform in size with a clearly visible nucleus. Trypan blue staining and non
radioactive cell proliferation assay were used to detect the cell survival rate.
Further, we provide optimum culture conditions which include cell density (1 *
10(7) cells/mL), culture medium (Leibovitz's L-15), pH (7.2-7.4), temperature (26
degrees C), and adherent time (24 h). Macrophages have been identified by
nonspecific esterase and Wright-Giemsa staining and have shown to grow very well.
In addition, the macrophages have a very strong bactericidal activity against
three kinds of bacteria, further verifying good growth conditions and proper
function.
PMID- 26427709
TI - The Wolbachia WO bacteriophage proteome in the Aedes albopictus C/wStr1 cell
line: evidence for lytic activity?
AB - Wolbachia pipientis (Rickettsiales), an obligate intracellular
alphaproteobacterium in insects, manipulates host reproduction to maximize
invasion of uninfected insect populations. Modification of host population
structure has potential applications for control of pest species, particularly if
Wolbachia can be maintained, manipulated, and genetically engineered in vitro.
Although Wolbachia maintains an obligate mutualism with genome stability in
nematodes, arthropods can be co-infected with distinct Wolbachia strains, and
horizontal gene transfer between strains is potentially mediated by WO phages
encoded within Wolbachia genomes. Proteomic analysis of a robust, persistent
infection of a mosquito cell line with wStr from the planthopper, Laodelphax
striatellus, revealed expression of a full array of WO phage genes, as well as
nine of ten non-phage genes that occur between two distinct clusters of WOMelB
genes in the genome of wMel, which infects Drosophila melanogaster. These non
phage genes encode potential host-adaptive proteins and are expressed in wStr at
higher levels than phage structural proteins. A subset of seven of the non-phage
genes is flanked by highly conserved non-coding sequences, including a putative
promoter element, that are not present in a syntenically arranged array of
homologs in plasmids from three tick-associated Rickettsia spp. These studies
expand our understanding of wStr in a host cell line derived from the mosquito,
Aedes albopictus, and provide a basis for investigating conditions that favor the
lytic phase of the WO phage life cycle and recovery of infectious phage
particles.
PMID- 26427710
TI - Development of primary cell cultures using hemocytes and phagocytic tissue cells
of Locusta migratoria: an application for locust immunity studies.
AB - Insect cell cultures played central roles in unraveling many insect physiological
and immunological processes. Regardless, despite imminent needs, insect cell
lines were developed primarily from Dipteran and Lepidopteran orders, leaving
many important insects such as Orthopteran locusts under-represented. Besides the
lack of cell lines, the slow progress in development of in vitro techniques is
attributed to poor communications between different laboratories regarding
optimized primary cell cultures. Therefore, we report here about methods
developed for primary cell culture of Locusta migratoria hemocyte and phagocytic
tissue cells by which we could maintain viable hemocytes in vitro for over 5 d
and phagocytic tissue cells for over 12 d. 2-Mercaptoethanol and phenyl-thiourea
supplements in Grace's medium together with addition of fetal bovine serum 30 min
after cell seeding resulted in a successful setup of the primary cell cultures
and a week-long survival of the hemocytes and phagocytic tissue cells in vitro.
PMID- 26427711
TI - Anticancer effect of rapamycin on MCF-7 via downregulation of VEGF expression.
AB - The importance of mTOR signaling in tumor biology is widely accepted and a number
of agents that selectively target mTOR are being developed in cancer therapy. On
the other hand, it has been demonstrated that mTOR can act as an angiogenic
agent. Thus, we hypothesized that the mTOR inhibitor-induced anticancer effect is
affected by expression of a key angiogenic factor, vascular endothelial growth
factor (VEGF) and investigated the anticancer effect underlying mTOR using an in
vitro assay. The mTOR inhibitor rapamycin dose-dependently reduced the cell
viability of the breast cancer cell line, MCF-7, but did not reduce the cell
viability of the colon cancer cell line, HT-29. Rapamycin reduced the VEGF
expression in the culture medium of MCF-7, while rapamycin did not contribute
VEGF expression in the culture medium of HT-29. VEGF stimulated cell viability
and VEGF inhibition reduced cell viability of MCF-7, and rapamycin dose
dependently restored the cell viability of MCF-7 reduced by rapamycin. These
findings suggest that mTOR acts as a direct anticancer agent and that the mTOR
inhibitor-induced anticancer effect involved the reduced expression of VEGF in
MCF-7. Our results imply that mTOR regulates the expression of VEGF and is
involved in breast cancer progression.
PMID- 26427712
TI - Staurosporine induces chondrogenesis of chick embryo wing bud mesenchyme in
monolayer cultures through canonical and non-canonical TGF-beta pathways.
AB - Staurosporine has been known to induce chondrogenesis in monolayer cultures of
mesenchymal cells by dissolving actin stress fibers. The aim of this study was to
further elucidate how the alteration of actin filaments by staurosporine induces
chondrogenesis. Specifically, we examined whether the transforming growth factor
(TGF)-beta pathway is implicated. SB505124 strongly suppressed staurosporine
induced chondrogenesis without affecting the drug's action on the actin
cytoskeleton. Staurosporine increased the phosphorylation of TGF-beta receptor I
(TbetaRI) but had no significant effect on the expression levels of TGF-beta1,
TGF-beta2, TGF-beta3, TbetaRI, TbetaRII, and TbetaRIII. Phosphorylation of Smad2
and Smad3 was not increased by staurosporine. However, SB505124 almost completely
suppressed the phosphorylation of Smad2 and Smad3. In addition, inhibition of
Smad3 blocked staurosporine-induced chondrogenesis. Inhibition of Akt, p38
mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK)
suppressed chondrogenesis induced by staurosporine. Phosphorylation of Akt, p38
MAPK, and JNK was increased by staurosporine. SB505124 reduced the
phosphorylation of Akt and p38 MAPK, while it had no effect on the
phosphorylation of JNK. The phosphorylation level of extracellular signal
regulated kinase (ERK) was not significantly affected by staurosporine. In
addition, inhibition of ERK with PD98059 alone did not induce chondrogenesis.
Taken together, these results suggest that staurosporine induces chondrogenesis
through TGF-beta pathways including canonical Smads and non-canonical Akt and p38
MAPK signaling.
PMID- 26427714
TI - Glutaminase 1 is a potential biomarker for chronic post-surgical pain in the rat
dorsal spinal cord using differential proteomics.
AB - Chronic post-surgical pain (CPSP) is a normal and significant symptom in clinical
surgery, such as breast operation, biliary tract operation, cesarean operation,
uterectomy and thoracic operation. Severe chronic post-surgical pain could
increase post-surgical complications, including myocardial ischemia, respiratory
insufficiency, pneumonia and thromboembolism. However, the underlying mechanism
is still unknown. Herein, a rat CPSP model was produced via thoracotomy. After
surgery, in an initial study, 5 out of 12 rats after surgery showed a significant
decrease in mechanical withdrawal threshold and/or increase in the number of
acetone-evoked responses, and therefore classified as the CPSP group. The
remaining seven animals were classified as non-CPSP. Subsequently, open-chest
operation was performed on another 30 rats and divided into CPSP and non-CPSP
groups after 21-day observation. Protein expression levels in the dorsal spinal
cord tissue were determined by 12.5 % SDS-PAGE. Finally, differently expressed
proteins were identified by LC MS/MS and analyzed by MASCOT software, followed by
Gene Ontology cluster analysis using PANTHER software. Compared with the non-CPSP
group, 24 proteins were only expressed in the CPSP group and another 23 proteins
expressed differentially between CPSP and non-CPSP group. Western blot further
confirmed that the expression of glutaminase 1 (GLS1) was significantly higher in
the CPSP than in the non-CPSP group. This study provided a new strategy to
identify the spinal proteins, which may contribute to the development of chronic
pain using differential proteomics, and suggested that GLS1 may serve as a
potential biomarker for CPSP.
PMID- 26427713
TI - In vitro differentiation process of human Wharton's jelly mesenchymal stem cells
to male germ cells in the presence of gonadal and non-gonadal conditioned media
with retinoic acid.
AB - Human umbilical Wharton's jelly-derived mesenchymal stem cells (HWJMSCs) are the
best candidate to get plentiful stem cells and differentiate them to germ cells
under appropriate conditions to treat infertility. We sought to determine under
which conditions HWJMSCs could form male germ cells in vitro. So, HWJMSCs were
differentiated to male germ cells under a mixture of bone morphogenetic protein-4
(BMP-4) and testicular and placental culture condition (TCC and PCC) medium
followed by retinoic acid for 21 d. In the present study, the HWJMSCs were
obtained from Wharton's jelly of umbilical cords of male neonates delivered by
cesarean section. At the third passage, mesenchymal stem cell markers and
differentiation to osteocytes and adipocytes were investigated. Then, HWJMSCs
were induced to differentiate into male germ cells in the presence of BMP-4, all
trans retinoic acid, PCC, and TCC for 21 d. The profile of c-Kit, DDX4, Piwil2,
and Dazl gene expression was evaluated by qPCR and ICC. Data was analyzed by
ANOVA test. After 3 wk of treatment with different reagents, the morphology of
these spindle-like cells changed to shiny clusters and germ cell-specific markers
in mRNA were upregulated in both TCC + retinoic acid (RA) and BMP-4 + RA.
Induction of HWJMSCs with TCC in the presence of RA resulted in significant
upregulation (P <= 0.05) of all germ cell-specific genes (c-Kit 2.6795 +/- 0.75,
DDX4 4.3188 +/- 1.18, Piwil2 4.9962 +/- 1.55, Dazl 6.1199 +/- 0.78) compared to
control and PCC + RA. Our results indicated that TCC and RA are involved in human
germ cell development. Moreover, BMP signaling also induced differentiation. Our
findings provide a novel effective approach for generation of germ cells in vitro
and studying the interaction of germ cells with their niche. Our work represents
an essential step toward gaining knowledge of the molecular properties of HWJMSCs
in the field of cell therapy. We demonstrated that under a suitable situation,
HWJMSCs have the ability to differentiate into germ cells and this provides an
excellent pattern to study infertility cause and cure.
PMID- 26427716
TI - Direct conversion of astrocytes into neuronal cells by drug cocktail.
PMID- 26427718
TI - One-Step Conversion of Methyl Ketones to Acyl Chlorides.
AB - Treatment of aromatic and heteroaromatic methyl ketones with sulfur monochloride
and catalytic amounts of pyridine in refluxing chlorobenzene leads to the
formation of acyl chlorides. Both electron-rich and electron-poor aryl methyl
ketones can be used as starting materials. The resulting C1-byproduct depends on
the precise reaction conditions chosen.
PMID- 26427717
TI - Implication of cell-in-cell structures in the transmission of HIV to epithelial
cells.
PMID- 26427715
TI - MSX2 mediates entry of human pluripotent stem cells into mesendoderm by
simultaneously suppressing SOX2 and activating NODAL signaling.
AB - How BMP signaling integrates into and destabilizes the pluripotency circuitry of
human pluripotent stem cells (hPSCs) to initiate differentiation into individual
germ layers is a long-standing puzzle. Here we report muscle segment homeobox 2
(MSX2), a homeobox transcription factor of msh family, as a direct target gene of
BMP signaling and a master mediator of hPSCs' differentiation to mesendoderm.
Enforced expression of MSX2 suffices to abolish pluripotency and induce directed
mesendoderm differentiation of hPSCs, while MSX2 depletion impairs mesendoderm
induction. MSX2 is a direct target gene of the BMP pathway in hPSCs, and can be
synergistically activated by Wnt signals via LEF1 during mesendoderm induction.
Furthermore, MSX2 destabilizes the pluripotency circuitry through direct binding
to the SOX2 promoter and repression of SOX2 transcription, while MSX2 controls
mesendoderm lineage commitment by simultaneous suppression of SOX2 and induction
of NODAL expression through direct binding and activation of the Nodal promoter.
Interestingly, SOX2 can promote the degradation of MSX2 protein, suggesting a
mutual antagonism between the two lineage-specifying factors in the control of
stem cell fate. Together, our findings reveal crucial new mechanisms of
destabilizing pluripotency and directing lineage commitment in hPSCs.
PMID- 26427719
TI - Cost and Cost-Effectiveness of Students for Nutrition and eXercise (SNaX).
AB - OBJECTIVE: To examine the cost and cost-effectiveness of implementing Students
for Nutrition and eXercise (SNaX), a 5-week middle school-based obesity
prevention intervention combining school-wide environmental changes, multimedia,
encouragement to eat healthy school cafeteria foods, and peer-led education.
METHODS: Five intervention and 5 control middle schools (mean enrollment, 1520
students) from the Los Angeles Unified School District participated in a
randomized controlled trial of SNaX. Acquisition costs for materials and time and
wage data for employees involved in implementing the program were used to
estimate fixed and variable costs. Cost-effectiveness was determined using the
ratio of variable costs to program efficacy outcomes. RESULTS: The costs of
implementing the program over 5 weeks were $5433.26 per school in fixed costs and
$2.11 per student in variable costs, equaling a total cost of $8637.17 per
school, or $0.23 per student per day. This investment yielded significant
increases in the proportion of students served fruit and lunch and a significant
decrease in the proportion of students buying snacks. The cost-effectiveness of
the program, per student over 5 weeks, was $1.20 per additional fruit served
during meals, $8.43 per additional full-priced lunch served, $2.11 per additional
reduced-price/free lunch served, and $1.69 per reduction in snacks sold.
CONCLUSIONS: SNaX demonstrated the feasibility and cost-effectiveness of a middle
school-based obesity-prevention intervention combining school-wide environmental
changes, multimedia, encouragement to eat healthy school cafeteria foods, and
peer-led education. Its cost is modest and unlikely to be a significant barrier
to adoption for many schools considering its implementation.
PMID- 26427721
TI - Evaluating the Validity of a Two-stage Sample in a Birth Cohort Established from
Administrative Databases.
AB - BACKGROUND: When using administrative databases for epidemiologic research, a
subsample of subjects can be interviewed, eliciting information on undocumented
confounders. This article presents a thorough investigation of the validity of a
two-stage sample encompassing an assessment of nonparticipation and
quantification of the extent of bias. METHODS: Established through record linkage
of administrative databases, the Quebec Birth Cohort on Immunity and Health (n =
81,496) aims to study the association between Bacillus Calmette-Guerin
vaccination and asthma. Among 76,623 subjects classified in four Bacillus
Calmette-Guerin-asthma strata, a two-stage sampling strategy with a balanced
design was used to randomly select individuals for interviews. We compared
stratum-specific sociodemographic characteristics and healthcare utilization of
stage 2 participants (n = 1,643) with those of eligible nonparticipants (n =
74,980) and nonrespondents (n = 3,157). We used logistic regression to determine
whether participation varied across strata according to these characteristics.
The effect of nonparticipation was described by the relative odds ratio (ROR =
ORparticipants/ORsource population) for the association between sociodemographic
characteristics and asthma. RESULTS: Parental age at childbirth, area of
residence, family income, and healthcare utilization were comparable between
groups. Participants were slightly more likely to be women and have a mother born
in Quebec. Participation did not vary across strata by sex, parental birthplace,
or material and social deprivation. Estimates were not biased by
nonparticipation; most RORs were below one and bias never exceeded 20%.
CONCLUSIONS: Our analyses evaluate and provide a detailed demonstration of the
validity of a two-stage sample for researchers assembling similar research
infrastructures.
PMID- 26427722
TI - Re: Ambient Air Pollution and Early Manifestation of Type 1 Diabetes.
PMID- 26427720
TI - Transcriptional Regulation of Cytosolic Sulfotransferase 1C2 by Intermediates of
the Cholesterol Biosynthetic Pathway in Primary Cultured Rat Hepatocytes.
AB - Cytosolic sulfotransferase 1C2 (SULT1C2) is expressed in the kidney, stomach, and
liver of rats; however, the mechanisms regulating expression of this enzyme are
not known. We evaluated transcriptional regulation of SULT1C2 by mevalonate (MVA)
derived intermediates in primary cultured rat hepatocytes using several
cholesterol synthesis inhibitors. Blocking production of mevalonate with the 3
hydroxy-3-methylglutaryl-CoA reductase inhibitor pravastatin (30 MUM), reduced
SULT1C2 mRNA content by ~40% whereas the squalene synthase inhibitor squalestatin
(SQ1, 0.1 MUM), which causes accumulation of nonsterol isoprenoids, increased
mRNA content by 4-fold. Treatment with MVA (10 mM) strongly induced SULT1C2 mRNA
by 12-fold, and this effect was blocked by inhibiting squalene epoxidase but not
by more distal cholesterol inhibitors, indicating the effects of MVA are mediated
by postsqualene metabolites. Using rapid amplification of cDNA ends (RACE), we
characterized the 5' end of SULT1C2 mRNA and used this information to generate
constructs for promoter analysis. SQ1 and MVA increased reporter activity by ~1.6
and 3-fold, respectively, from a construct beginning 49 base pairs (bp) upstream
from the longest 5'-RACE product (-3140:-49). Sequence deletions from this
construct revealed a hepatocyte nuclear factor 1 (HNF1) element (-2558), and
mutation of this element reduced basal (75%) and MVA-induced (30%) reporter
activity and attenuated promoter activation following overexpression of HNF1alpha
or 1beta. However, the effects of SQ1 were localized to a more proximal promoter
region (-281:-49). Collectively, our findings demonstrate that cholesterol
biosynthetic intermediates influence SULT1C2 expression in rat primary
hepatocytes. Further, HNF1 appears to play an important role in mediating basal
and MVA-induced SULT1C2 transcription.
PMID- 26427723
TI - Quantifying Protection Against Influenza Virus Infection Measured by
Hemagglutination-inhibition Assays in Vaccine Trials.
AB - BACKGROUND: Correlations between hemagglutination-inhibition titers (hereafter
"titers") and protection against infection have been identified in historical
studies. However, limited information is available about the dynamics of how
titer influences protection. METHODS: Titers were measured in randomized, placebo
controlled vaccine trials in Hong Kong among pediatrics during September 2009
December 2010 and the United States among adults during Oct 2007-April 2008.
Intermediate unobserved titers were imputed using three interpolation methods. As
participants were recruited at different times leading to varying exposure to
infection relative to entry, a modified proportional hazards model was developed
to account for staggered entry into the studies and to quantify the correlation
of titers with protection against influenza infections, adjusting for waning in
titers. The model was fitted using Markov chain Monte Carlo and importance
sampling. RESULTS: A titer of 1:40 was associated with a reduced infection risk
of 40%-70% relative to a titer of 1:10, depending on the circulating strain; the
corresponding protection associated with a titer of 1:80 was 54%-84%. Results
were robust across interpolation methods. The trivalent-inactivated vaccine
reduced cumulative incidence of influenza B and influenza A(H3N2) infections by
six percentage points (pp; 95% credible interval = 2 pp, 10 pp) and 1 pp (95%
credible interval = 0.3 pp, 2 pp) respectively, but not for influenza
A(H1N1)pdm09. The live-attenuated vaccine showed little efficacy against
influenza A(H3N2) infections. CONCLUSIONS: Titers are correlated with protection
against influenza infections. The trivalent inactivated vaccine can reduce the
risk of influenza A(H3N2) and influenza B infections in the community.
PMID- 26427724
TI - Maternal Leisure Time Physical Activity and Infant Birth Size.
AB - BACKGROUND: Associations of maternal leisure time physical activity with birth
size are inconsistent. Roles of infant sex and maternal prepregnancy body mass
index (BMI) in these associations have not been studied. METHODS: Participants (N
= 3,310) in the Omega study, a cohort in Washington State (1996-2008), reported
leisure time physical activity duration and energy expenditure in the year
prepregnancy and in early pregnancy (mean 15 weeks gestation). Regression models
estimated mean differences in infant head circumference, birthweight, and
ponderal index (birthweight/length) across quartiles of pre- or early-pregnancy
leisure time physical activity. We assessed effect modification by infant sex or
prepregnancy overweight/obese status (BMI >= 25 kg/m). RESULTS: We observed
positive associations between prepregnancy leisure time physical activity and
head circumference overall and among male infants. Among males, each quartile
increase in prepregnancy physical activity duration was associated with 0.14 cm
(95% confidence interval = 0.046, 0.24; trend P = 0.004) greater head
circumference. We did not observe associations between leisure time physical
activity and birthweight or ponderal index overall. Each quartile increase in pre
or early-pregnancy physical activity duration was associated with 17-23 g lower
birthweight among female infants and among women with normal prepregnancy BMI.
CONCLUSIONS: We observed positive associations between prepregnancy leisure time
physical activity and head circumference among male infants, and inverse
associations of pre- and early-pregnancy physical activity with birthweight among
female infants and women with normal prepregnancy BMI. Future studies should
confirm results and elucidate mechanisms of observed associations.
PMID- 26427726
TI - European regulation of continuing professional development won't improve quality
of care.
PMID- 26427725
TI - Interpreting Seroepidemiologic Studies of Influenza in a Context of Nonbracketing
Sera.
AB - BACKGROUND: In influenza epidemiology, analysis of paired sera collected from
people before and after influenza seasons has been used for decades to study the
cumulative incidence of influenza virus infections in populations. However,
interpretation becomes challenging when sera are collected after the start or
before the end of an epidemic, and do not neatly bracket the epidemic. METHODS:
Serum samples were collected longitudinally in a community-based study. Most
participants provided their first serum after the start of circulation of
influenza A(H1N1)pdm09 virus in 2009. We developed a Bayesian hierarchical model
to correct for nonbracketing sera and estimate the cumulative incidence of
infection from the serological data and surveillance data in Hong Kong. RESULTS:
We analyzed 4,843 sera from 2,097 unvaccinated participants in the study,
collected from April 2009 to December 2010. After accounting for nonbracketing,
we estimated that the cumulative incidence of H1N1pdm09 virus infection was 45%
(95% credible interval [CI] = 40%, 49%), 17% (95% CI = 13%, 20%), and 11% (95% CI
= 6%, 18%) for children ages 0-18 years, adults 19-50 years, and older adults >50
years, respectively. Including all available data substantially increased
precision compared with a simpler analysis based only on sera collected at 6
month intervals in a subset of participants. CONCLUSIONS: We developed a
framework for the analysis of antibody titers that accounted for the timing of
sera collection with respect to influenza activity and permitted robust
estimation of the cumulative incidence of infection during an epidemic.
PMID- 26427727
TI - Telomere dynamics in patients with del (5q) MDS before and under treatment with
lenalidomide.
AB - Myelodysplastic syndrome (MDS) associated with an acquired, isolated deletion of
chromosome 5q (del (5q) MDS), represent a clonal disorder of hematopoiesis and a
clinically distinct entity of MDS. Treatment of del (5q) MDS with the drug
lenalidomide has significantly improved quality of life leading to transfusion
independence and complete cytogenetic response rates (CCR) in the majority of
patients. Telomeres are located at the end of eukaryotic chromosomes and are
linked to replicative history/potential as well as genetic (in) stability of
hematopoietic stem cells. Here, we analyzed telomere length (TL) dynamics before
and under lenalidomide treatment in the peripheral blood and/or bone marrow of
del (5q) patients enrolled in the LEMON-5 study (NCT01081431). Hematopoietic
cells from del (5q) MDS patients were characterized by significantly shortened TL
compared to age-matched healthy controls. Telomere loss was more accelerated in
patients with longer disease duration (>2 years) and more pronounced cytopenias.
Sequential analysis under lenalidomide treatment revealed that previously
shortened TL in peripheral blood cells was significantly "elongated" towards
normal levels within the first six months suggesting a shift from clonal del (5q)
cells towards normal hematopoiesis in lenalidomide treated MDS patients. Taken
together our findings suggest that the development of the del (5q) clone is
associated with accelerated telomere shortening at diagnosis. However, upon
induction of CCR and reoccurrence of normal hematopoiesis, the lack of a
persistent TL deficit argues against telomere-mediated genetic instability
neither as a disease-promoting event of del (5q) MDS nor for lenalidomide
mediated development of secondary primary malignancies of the hematopoietic
system in responding patients.
PMID- 26427728
TI - Comparison of immune manifestations between refractory cytopenia of childhood and
aplastic anemia in children: A single-center retrospective study.
AB - This retrospective single-center study assessed the incidence and clinical
features of immune manifestations of refractory cytopenia of childhood (RCC) and
childhood aplastic anemia (AA). We evaluated 72 children with RCC and 123 with AA
between February 2008 and March 2013. RCC was associated with autoimmune disease
in 4 children, including 1 case each with autoimmune hemolytic anemia, rheumatoid
arthritis, systemic lupus erythematosus, and anaphylactoid purpura. No children
with AA were diagnosed with autoimmune diseases. Immune abnormalities were common
in both RCC and AA; the most significant reductions were in the relative numbers
of CD3-CD56+ subsets found in RCC. Despite the many similar immunologic
abnormalities in AA and RCC, the rate of autoimmune disease was significantly
lower in childhood AA than RCC (p=0.008, chi2=6.976). The relative numbers of
natural killer cells were significantly lower in RCC patients than AA patients.
By month 6, there was no significant difference in autoimmune manifestations
between RCC and AA in relation to the response to immunosuppressive therapy
(p=0.907, chi2=0.014). The large overlap of analogous immunologic abnormalities
indicates that RCC and childhood AA may share the same pathogenesis.
PMID- 26427729
TI - Secondary acute lymphoblastic leukemia is an independent predictor of poor
prognosis.
AB - Compared to secondary acute myeloid leukemia, secondary acute lymphoblastic
leukemia (sALL) is poorly characterized. We utilized data from the Surveillance,
Epidemiology, and End Results (SEER) 13 database to further elucidate patient
characteristics and prognostic factors in sALL. Cases of adult de novo acute
lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum,
cervix, or ovarian cancers or lymphoma with a latency period of at least 12
months were identified within the SEER 13 database. Survival in sALL and de novo
ALL were compared after propensity matching based on age, gender, race, ALL
subtype, and year of diagnosis. 4124 cases of de novo ALL and 79 cases of sALL
were identified. sALL patients were older at diagnosis (median 62 years vs. 44
years; p<0.01). Overall survival (OS) in sALL was lower than de novo ALL (median
8 months vs. 11 months), 1 year OS: 35% vs. 47% (p=0.05), 2 year OS: 16% vs. 31%
(p<0.01), and 5 year OS: 7% vs. 21% (p<0.01). Multivariate analysis revealed sALL
as an independent predictor of worsened survival (adjusted HR 1.54; 95% CI 1.16
2.04, p<0.01) after propensity matching.
PMID- 26427730
TI - Quantitative PCR for the diagnosis of cutaneous leishmaniasis from formalin-fixed
and paraffin-embedded skin sections.
AB - The present report describes a real-time PCR-based procedure to reliably
determine the quantity of Leishmania amastigotes in relation to the amount of
host tissue in histological skin sections from canine and equine cases of
cutaneous leishmaniasis. The novel diagnostic Leishmania-PCR has a detection
limit of <0.02 amastigotes per MUg tissue, which corresponds well to the
detection limit of immunohistochemistry and is far beyond that of conventional
histology. Our results emphasise the importance of PCR to complement routine
histology of cutaneous leishmaniasis cases, particularly in laboratories in which
no immunohistochemical assay is available.
PMID- 26427731
TI - Developmental expression of Kir4.1 in astrocytes and oligodendrocytes of rat
somatosensory cortex and hippocampus.
AB - Kir4.1 is the principal K(+) channel expressed in glial cells. It has been shown
that it plays a fundamental role in K(+)-spatial buffering, an astrocyte-specific
process where excess extracellular concentration of K(+) ions, generated by
synaptic activity, is spatially redistributed to distant sites via astrocytic
syncytia. Experimental and clinical evidence suggested that abnormality of Kir4.1
function in the brain is involved in different neurological diseases such as
epilepsy, dysmyelination, and Huntington's disease. Although it has been shown
that Kir4.1 is expressed predominantly in astrocytes in certain areas of the rat
brain and its transcript is present in the rat forebrain as early as embryonic
day E14, no information is available concerning the temporal sequence of Kir4.1
protein appearance during embryonic and post-natal development. Aim of this work
was to study the expression pattern of Kir4.1 channel in rat somatosensory cortex
and hippocampus during development and to examine its cellular localization with
the glial and oligodendroglial markers S100-beta, GFAP, and Olig-2. Kir4.1
protein was detected since E20 and a gradual increase of Kir4.1 expression
occurred between early postnatal period and adulthood. We showed a gradual shift
in Kir4.1 subcellular localization from the soma of astrocytes to distal glial
processes. Double immunofluorescence experiments confirmed the cellular
localization of Kir4.1 in glial cells. Our data provide the first overview of
Kir4.1 developmental expression both in the cortex and hippocampus and support
the glial role of Kir4.1 in K(+) spatial buffering.
PMID- 26427732
TI - Interaction between Pseudomonas aeruginosa and dermatophyte fungi: Repercussions
on the clinical course and microbiological diagnosis of tinea pedis.
PMID- 26427733
TI - New Information Technologies in Dermatology Education: Dermaconsulta--a Virtual
Patient Tool.
PMID- 26427734
TI - Neutrophilic Dermatoses Associated With Autoimmunity.
PMID- 26427735
TI - Why Is Mohs Micrographic Surgery Underused in the Treatment of
Dermatofibrosarcoma Protuberans in Children?
PMID- 26427736
TI - Comment on "Hidradenitis Suppurativa: New Opportunities for an Orphan Skin
Disease".
PMID- 26427737
TI - Usefulness of Photodynamic Therapy in the Management of Onychomycosis.
AB - Onychomycosis, or fungal infection of the nails, is one of the most prevalent
fungal diseases in the general population. Treatment is of limited effectiveness,
tedious, and must be administered for long periods. Furthermore, systemic
antifungal agents are associated with adverse effects. Photodynamic therapy (PDT)
may prove to be a viable alternative in the treatment of superficial skin
infections, including onychomycosis. We review articles relating to the
usefulness of PDT in onychomycosis in both in vitro and in vivo settings and
discuss the potential and limitations of various photosensitizing agents. In
vivo, methylene blue and 5-aminolevulinic acid have led to cure rates in 80% and
43% of cases, respectively, at 12 months. Finally, based on data in the
literature and our own experience, we propose a protocol of 3 PDT sessions,
separated by an interval of 1 or 2 weeks, using methyl aminolevulinate 16% as a
photosensitizing agent and red light (lambda=630 nm, 37 J.cm(-2)). Each session
is preceded by the topical application of urea 40% over several days. Clinical
trials are needed to optimize PDT protocols and to identify those patients who
will benefit most from this treatment.
PMID- 26427738
TI - Aging and Parkinson's disease as functional models of temporal order perception.
AB - OBJECTIVE: Our study evaluates how aging and Parkinson's disease (PD) alter
temporal order judgment (TOJ). METHOD: Two TOJ experiments were performed with
young participants, healthy elderly participants, and PD patients. Two white
squares were presented on opposite sides of a screen and participants responded
which appeared first. In Experiment 1, it was assessed how accurately each group
could judge temporal order at intervals from 0ms to 167ms. Detectability, the
capacity of detecting which stimulus appeared first, was measured. In Experiment
2, participants were asked to orient their attention to the hemifield indicated
by a cue. The PSS ("point of subjective simultaneity"), where the participant was
equally likely to respond that either stimulus appeared first, was measured.
RESULTS: In Experiment 1, PD patients had smaller detectability than healthy
elderly (p<0.05) and young participants (p<0.001), and healthy elderly
participants had smaller detectability than young participants (p<0.001). In
Experiment 2, PSS was 29ms for young participants, 121ms for healthy elderly
participants, and 283ms for PD patients; differences were statistically
significant for comparisons between PD patients and healthy elderly participants
(p<0.001), PD patients and young participants (p<0.001), and healthy elderly and
young participants (p<0.04). CONCLUSIONS: TOJ is impaired by aging and PD. Our
results suggest that dopamine loss increases latency and variability in visual
decision making due to a lower signal-to-noise ratio in the visual pathways.
PMID- 26427739
TI - Synaesthetic interactions across vision and audition.
AB - In everyday life our senses are exposed to a constant influx of sensory signals.
The brain binds signals into a coherent percept based on temporal, spatial or
semantic correspondences. In addition, synaesthetic correspondences may form
important cues for multisensory binding. This study focussed on the synaesthetic
correspondences between auditory pitch and visual size. While high pitch has been
associated with small objects in static contexts, recent research has
surprisingly found that increasing size is linked with rising pitch. The current
study presented participants with small/large visual circles/discs together with
high/low pitched pure tones in an intersensory selective attention paradigm.
Whilst fixating a central cross participants discriminated between small and
large visual size in the visual modality or between high and low pitch in the
auditory modality. Across a series of five experiments, we observed convergent
evidence that participants associated small visual size with low pitch and large
visual size with high pitch. In other words, we observed the pitch-size mapping
that has previously been observed only for dynamic contexts. We suggest that
these contradictory findings may emerge because participants can interpret visual
size as an index of permanent object size or distance (e.g. in motion) from the
observer. Moreover, the pitch-size mapping may depend not only on relative but
also on the absolute levels of pitch and size of the presented stimuli.
PMID- 26427740
TI - Measurement of Load Redistribution Properties of Wheelchair Cushions Using a
Compliant Cushion Loading Indenter.
AB - The aim of this project was to develop and validate a compliant cushion loading
indenter (CCLI) capable of evaluating wheelchair cushion performance by measuring
internal pressures and deflection. The design of the CCLI consists of 3
subsystems: 1) an internal substructure with medial and lateral protuberances to
mimic the load-bearing ischial tuberosities and trochanters, 2) an elastomeric
shell to mimic soft tissue and 3) instrumentation to measure internal pressures
at both protuberances and deflection of the elastomer at 7 locations. It is
parametrically designed so can be scaled larger or smaller to represent different
body sizes. To assess the repeatability and sensitivity of measurements, the
model was loaded onto two wheelchair cushions, 3" flat foam and Jay3, using two
loads, 44kgf and 53kgf, representing the average upper body mass of 70kg and 83kg
persons, respectively. The results showed a high precision of pressure and
deflection measurement across two different cushions and loads. Under both loads,
pressure measurements exhibited a standard error of < 1 mm and <3 mmHg. The
standard deviations of deflection values were less than 2.5 mm (0.1 in.). The
pressures and absolute deflection differed significantly across load and cushion
type indicating sensitivity to change.
PMID- 26427741
TI - Automatic Adjustment of Keyboard Settings Can Enhance Typing.
AB - We developed and evaluated a software tool for the automatic configuration of
Windows keyboard settings. The software is intended to accommodate the needs of
people with physical impairments, with a goal of improved productivity and
comfort during typing. The prototype software, called AutoIDA, monitors user
activity during performance of regular computer tasks and recommends the Sticky
Keys and key repeat settings to meet the user's specific needs. The evaluation
study included fourteen individuals with upper extremity impairments. AutoIDA
recommended changes to the default keyboard settings for 10 of the 14
participants. For these individuals, average typing speed was essentially the
same whether users typed with the default keyboard settings (5.5 wpm) or the
AutoIDA-recommended settings (5.3 wpm). Average typing errors decreased with use
of the recommended settings, from 17.6% to 13.3%, but this was not quite
statistically significant (p = .10). On an individual basis, four participants
appeared to improve their overall typing performance with AutoIDA-recommended
settings. For more specific metrics, AutoIDA prevented about 90% of inadvertent
key repeats (with a revised algorithm) and increased the efficiency and accuracy
of entering modified (shifted) characters. Participants agreed that software like
AutoIDA would be useful to them (average rating 4.1, where 5 = strongly agree).
PMID- 26427743
TI - A Low-Cost Audio Prescription Labeling System Using RFID for Thai Visually
Impaired People.
AB - This research aims to develop a low-cost audio prescription labeling (APL) system
for visually-impaired people by using the RFID system. The developed APL system
includes the APL machine and APL software. The APL machine is for visually
impaired people while APL software allows caregivers to record all important
information into the APL machine. The main objective of the development of the
APL machine is to reduce costs and size by designing all of the electronic
devices to fit into one print circuit board. Also, it is designed so that it is
easy to use and can become an electronic aid for daily living. The developed APL
software is based on Java and MySQL, both of which can operate on various
operating platforms and are easy to develop as commercial software. The developed
APL system was first evaluated by 5 experts. The APL system was also evaluated by
50 actual visually-impaired people (30 elders and 20 blind individuals) and 20
caregivers, pharmacists and nurses. After using the APL system, evaluations were
carried out, and it can be concluded from the evaluation results that this
proposed APL system can be effectively used for helping visually-impaired people
in terms of self-medication.
PMID- 26427744
TI - Usability of a Low-Cost Head Tracking Computer Access Method following Stroke.
AB - Assistive technology devices for computer access can facilitate social
reintegration and promote independence for people who have had a stroke. This
work describes the exploration of the usefulness and acceptability of a new
computer access device called the NouseTM (Nose-as-mouse). The device uses
standard webcam and video recognition algorithms to map the movement of the
user's nose to a computer cursor, thereby allowing hands-free computer operation.
Ten participants receiving in- or outpatient stroke rehabilitation completed a
series of standardized and everyday computer tasks using the NouseTM and then
completed a device usability questionnaire. Task completion rates were high (90%)
for computer activities only in the absence of time constraints. Most of the
participants were satisfied with ease of use (70%) and liked using the NouseTM
(60%), indicating they could resume most of their usual computer activities apart
from word-processing using the device. The findings suggest that hands-free
computer access devices like the NouseTM may be an option for people who
experience upper motor impairment caused by stroke and are highly motivated to
resume personal computing. More research is necessary to further evaluate the
effectiveness of this technology, especially in relation to other computer access
assistive technology devices.
PMID- 26427745
TI - Design of a Braille Learning Application for Visually Impaired Students in
Bangladesh.
AB - Visually impaired students (VIS) are unable to get visual information, which has
made their learning process complicated. This paper discusses the overall
situation of VIS in Bangladesh and identifies major challenges that they are
facing in getting education. The Braille system is followed to educate blind
students in Bangladesh. However, lack of Braille based educational resources and
technological solutions have made the learning process lengthy and complicated
for VIS. As a developing country, Bangladesh cannot afford for the costly Braille
related technological tools for VIS. Therefore, a mobile phone based Braille
application, "mBRAILLE", for Android platform is designed to provide an easy
Braille learning technology for VIS in Bangladesh. The proposed design is
evaluated by experts in assistive technology for students with disabilities, and
advanced learners of Braille. The application aims to provide a Bangla and
English Braille learning platform for VIS. In this paper, we depict iterative
(participatory) design of the application along with a preliminary evaluation
with 5 blind subjects, and 1 sighted and 2 blind experts. The results show that
the design scored an overall satisfaction level of 4.53 out of 5 by all
respondents, indicating that our design is ready for the next step of
development.
PMID- 26427746
TI - Design and Evaluation of the Kinect-Wheelchair Interface Controlled (KWIC) Smart
Wheelchair for Pediatric Powered Mobility Training.
AB - BACKGROUND: Children with severe disabilities are sometimes unable to access
powered mobility training. Thus, we developed the Kinect-Wheelchair Interface
Controlled (KWIC) smart wheelchair trainer that converts a manual wheelchair into
a powered wheelchair. The KWIC Trainer uses computer vision to create a virtual
tether with adaptive shared-control between the wheelchair and a therapist during
training. It also includes a mixed-reality video game system. METHODS: We
performed a year-long usability study of the KWIC Trainer at a local clinic,
soliciting qualitative and quantitative feedback on the device after extended
use. RESULTS: Eight therapists used the KWIC Trainer for over 50 hours with 8
different children. Two of the children obtained their own powered wheelchair as
a result of the training. The therapists indicated the device allowed them to
provide mobility training for more children than would have been possible with a
demo wheelchair, and they found use of the device to be as safe as or safer than
conventional training. They viewed the shared control algorithm as counter
productive because it made it difficult for the child to discern when he or she
was controlling the chair. They were enthusiastic about the video game
integration for increasing motivation and engagement during training. They
emphasized the need for additional access methods for controlling the device.
CONCLUSION: The therapists confirmed that the KWIC Trainer is a useful tool for
increasing access to powered mobility training and for engaging children during
training sessions. However, some improvements would enhance its applicability for
routine clinical use.
PMID- 26427747
TI - Rare adverse events due to house dust mite sublingual immunotherapy in pediatric
practice: two case reports.
AB - Sublingual route, a noninjective way of allergen administration appears to be
associated with a lower incidence of severe systemic reactions compared with the
subcutaneous route. Local adverse reactions are reported which resolve
spontaneously within a few days without need for discontinuation of treatment.
Hereby, we report two pediatric cases, one with persistent asthma and the other
one with persistent allergic rhinitis. Both were treated by house dust mite
sublingual immunotherapy, one of whom developed severe wheezing (grade 2 systemic
reaction based on World Allergy Organization subcutaneous systemic reaction
grading system) and the other intractable vomiting (grade 3 local reaction based
on World Allergy Organization sublingual immunotherapy local adverse events
grading system) at the end of the build-up phase which repeated on re
administration of the same dose. Both of those two cases completed their 3-year
immunotherapy successfully by patient-based adjustment of the highest tolerated
dose of the maintenance.
PMID- 26427748
TI - Adhesive Nanoparticles as Local Probes of Membrane Curvature.
AB - Biological and biomimetic membranes display complex shapes with nonuniform
curvature. Because the interaction of adhesive nanoparticles with such membranes
depends on the local membrane curvature, different segments of the same membrane
can differ in their engulfment behavior. For a single vesicle in contact with
many nanoparticles, we predict ten distinct engulfment patterns as well as
morphological transitions between these patterns, which are directly accessible
to experiment.
PMID- 26427749
TI - Transcriptomic Responses During Early Development Following Arsenic Exposure in
Western Clawed Frogs, Silurana tropicalis.
AB - Arsenic compounds are widespread environmental contaminants and exposure elicits
serious health issues, including early developmental anomalies. Depending on the
oxidation state, the intermediates of arsenic metabolism interfere with a range
of subcellular events, but the fundamental molecular events that lead to
speciation-dependent arsenic toxicity are not fully elucidated. This study
therefore assesses the impact of arsenic exposure on early development by
measuring speciation and gene expression profiles in the developing Western
clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5
and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid,
arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected.
Microarray and pathway analyses were utilized to characterize the comprehensive
transcriptomic responses to arsenic exposure. Clustering analysis of expression
data showed distinct gene expression patterns in arsenate treated groups when
compared with the control. Pathway enrichment revealed common biological themes
enriched in both treatments, including cell signal transduction, cell survival,
and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment
of pathways and biological processes involved in arsenic intake or efflux, as
well as histone remodeling. These compensatory responses are hypothesized to be
responsible for maintaining an in-body arsenic level comparable to control
animals. With no appreciable changes observed in malformation and mortality
between control and exposed larvae, this is the first study to suggest that the
underlying transcriptomic regulations related to signal transduction, cell
survival, developmental pathways, and histone remodeling may contribute to
maintaining ongoing development while coping with the potential arsenic toxicity
in S. tropicalis during early development.
PMID- 26427750
TI - Anti-inflammatory strategies in the treatment of schizophrenia.
AB - Schizophrenia is a major mental illness with a lifetime prevalence of about 1%.
Antipsychotic drugs, with a primary mechanism of action that involves dopamine
receptor blockade, are the mainstay in the treatment of the disorder. However,
despite optimum antipsychotic treatment, few patients return to pre-morbid
levels; the treatment deficit includes refractory positive symptoms, negative
symptoms, mood impairments, cognitive impairments, social impairments, and/or a
variety of medication-related adverse effects, including extrapyramidal symptoms,
metabolic disturbances, hyperprolactinemia, and others. To address these,
antipsychotic treatment has been augmented with psychosocial interventions,
cognitive rehabilitation, different kinds of electrical and magnetic brain
stimulation, and a large range of drugs from the neuropsychiatric as well as,
surprise, the general medical pharmacopeia. The pleomorphic pathophysiology of
schizophrenia includes abnormalities in immunological and inflammatory pathways,
and so it is not surprising that anti-inflammatory drugs have also been trialed
as augmentation agents in schizophrenia. This article critically examines the
outcomes after augmentation with conventional anti-inflammatory interventions;
results from randomized controlled trials do not encourage the use of either
aspirin (1000 mg/day) or celecoxib (400 mg/day), both of which have been studied
for this indication during the past decade and a half.
PMID- 26427752
TI - Erratum to: Intermittent high dose proton pump inhibitor enhances the antitumor
effects of chemotherapy in metastatic breast cancer.
PMID- 26427754
TI - Editorial: preventing disease progression in Crohn's--can we shut the stable door
before the horse bolts?
PMID- 26427753
TI - Self-reported care needs of Dutch homeless people with and without a suspected
intellectual disability: a 1.5-year follow-up study.
AB - Cognitive impairment is a prevalent problem among the homeless and seems related
to more psychosocial problems. However, little is known about the care needs of
the subgroup of homeless people with an intellectual disability compared to those
without an intellectual disability and how their care needs develop over time.
This study explores self-reported care needs within a broad range of life domains
among Dutch homeless people with and without a suspected intellectual disability
to gain insight into the transition of self-reported care needs from baseline to
follow-up in both subgroups. This longitudinal study is part of a cohort study
among homeless people who had been accepted for an individual programme plan in
four major Dutch cities. The initial cohort consisted of 513 participants who
were interviewed in 2011. At 1.5-year follow-up, 336 participants (65.5%) were
also interviewed and screened for intellectual disability. Of these participants,
31% (95% CI 26.2-36.1) had a suspected intellectual disability. For both groups,
between baseline and follow-up, the number of 'unmet care needs' decreased
significantly and the number of 'no care needs' increased significantly, while at
follow-up, participants with a suspected intellectual disability reported 'no
care needs' on significantly fewer life domains than those without a suspected
intellectual disability (mean numbers 16.4 vs. 17.5). Between baseline and follow
up, 'met care needs' decreased significantly on housing for both groups, and
increased on finances and dental care for participants with a suspected
intellectual disability. At follow-up, participants with a suspected intellectual
disability more often preferred housing support available by appointment than
those without a suspected intellectual disability. These findings suggest that
homeless people who had been accepted for an individual programme plan with a
suspected intellectual disability have care needs for a longer period of time
than those without a suspected intellectual disability. Providing care to
homeless people with a suspected intellectual disability might require ongoing
care and support, also after exiting homelessness. Support services should take
this into account when considering their care provision and planning of services.
PMID- 26427755
TI - Letter: infliximab therapy for patients with inflammatory bowel disease--some
unanswered questions.
PMID- 26427756
TI - Letter: infliximab therapy for patients with inflammatory bowel disease--some
unanswered questions. Authors' reply.
PMID- 26427757
TI - Corrigendum.
AB - In the paper 'Population pharmacokinetics-pharmacodynamics of vedolizumab in
patients with ulcerative colitis and Crohn's disease' published in Volume 42,
Issue 2 (July 2015), an error was found on page 2, column 1 last paragraph-the
unit used for the concentration is incorrect. It should be 1-10 MUg/mL instead of
1-10 ng/mL. The sentence should read 'After reaching peak concentrations,
vedolizumab serum concentrations fell in a generally biexponential fashion until
concentrations reached approximately 1-10 MUg/mL'.The authors apologise for this
error.
PMID- 26427758
TI - cIAP2 supports viability of mice lacking cIAP1 and XIAP.
PMID- 26427759
TI - Response to Heard et al.
PMID- 26427760
TI - The inner membrane histidine kinase EnvZ senses osmolality via helix-coil
transitions in the cytoplasm.
PMID- 26427761
TI - Identification of the Substrate Access Portal of 5-Lipoxygenase.
AB - The overproduction of inflammatory lipid mediators derived from arachidonic acid
contributes to asthma and cardiovascular diseases, among other pathologies.
Consequently, the enzyme that initiates the synthesis of pro-inflammatory
leukotrienes, 5-lipoxygenase (5-LOX), is a target for drug design. The crystal
structure of 5-LOX revealed a fully encapsulated active site; thus the point of
substrate entry is not known. We asked whether a structural motif, a "cork"
present in 5-LOX but absent in other mammalian lipoxygenases, might be ejected to
allow substrate access. Our results indicate that reduction of cork volume
facilitates access to the active site. However, if cork entry into the site is
obstructed, enzyme activity is significantly compromised. The results support a
model in which the "cork" that shields the active site in the absence of
substrate serves as the active site portal, but the "corking" amino acid Phe-177
plays a critical role in providing a fully functional active site. Thus, the more
appropriate metaphor for this structural motif is a "twist-and-pour" cap.
Additional mutagenesis data are consistent with a role for His-600, deep in the
elongated cavity, in positioning the substrate for catalysis.
PMID- 26427762
TI - Influence of developmental nicotine exposure on the ventilatory and metabolic
response to hyperthermia.
AB - To determine whether developmental nicotine exposure (DNE) alters the ventilatory
and metabolic response to hyperthermia in neonatal rats (postnatal age 2-4 days),
pregnant dams were exposed to nicotine (6 mg kg(-1) of nicotine tartrate daily)
or saline with an osmotic mini-pump implanted subdermally on day 5 of gestation.
Rat pups (a total of 72 controls and 72 DNE pups) were studied under
thermoneutral conditions (chamber temperature 33 degrees C) and during moderate
thermal stress (37.5 degrees C). In all pups, core temperature was similar to
chamber temperature, with no treatment effects. The rates of pulmonary
ventilation (V(I)), O2 consumption (V(O2)) and CO2 production (V(CO2)) did not
change with hyperthermia in either control or DNE pups. However, V(I) was lower
in DNE pups at both chamber temperatures, whereas the duration of spontaneous
apnoeas was longer in DNE pups than in controls at 33 degrees C. The V(I)/V(O2)
ratio increased at 37.5 degrees C in control pups, although it did not change in
DNE pups. To simulate severe thermal stress, additional pups were studied at 33
degrees C and 43 degrees C. V(I) increased with heating in control pups but not
in DNE pups. As heat stress continued, gasping was evoked in both groups, with no
effect of DNE on the gasping pattern. Over a 20 min recovery period at 33 degrees
C, V(I) returned to baseline in control pups but remained depressed in DNE pups.
In addition to altering baseline V(I) and apnoea duration, DNE is associated with
subtle but significant alterations in the ventilatory response to hyperthermia in
neonatal rats.
PMID- 26427763
TI - Role of aberrant IgG glycosylation in the pathogenesis of inflammatory bowel
disease.
AB - The intestine is one of the most important organs associated with the immune
system. It is thought that disruption of intestinal immunity causes inflammatory
bowel disease (IBD). Recent advances in immune glycobiology have provided novel
insights into many human diseases. For example, studies of glycosylation
remodeling in mice have underscored the importance of oligosaccharides in the
pathogenesis of IBD. Furthermore, aberrant glycosylation of IgG is a good serum
marker of IBD activity. In this review, we examine current understanding of the
role of aberrant glycosylation in the pathogenesis of IBD in terms of our
original data and recent reports.
PMID- 26427764
TI - Teatime Threats. Choking Incidents at the Evening Meal.
AB - PURPOSE: To explore caregiver perceptions of the socio-environmental issues
around evening meal ('teatime') which influence choking. Mealtime difficulties
for people with intellectual disabilities and/or mental illness may be
underdiagnosed. Difficulties affect quality of life with social aspects impacting
on service-users and caregivers. Reporting of choking incidents has increased
locally following widespread training. Analysis of reports showed most incidents
were occurring around evening meal. METHODOLOGY: A qualitative study of
caregivers witnessing a choking incident was undertaken. Semi-structured
interviews explored perceptions of the causes. Data were analysed using thematic
analysis. FINDINGS: Thematic analysis elicited individual service user
characteristics, and social and contextual factors implicated in choking. The
findings will facilitate risk assessment for service-users and inform mealtime
practice. Staff familiarity is a key factor. Further research involving service
users is indicated to complement these findings. This study widens the focus of
recent studies which have considered physical more than socio-environmental
aspects of mealtime difficulties.
PMID- 26427765
TI - Neuropsychological correlates of Pisa syndrome in patients with Parkinson's
disease.
AB - BACKGROUND: A complex relationship exists between postural control and cognition
in the elderly. Namely, neural mechanisms that are required for the regulation of
posture have been variably associated with cognitive dysfunctions. Parkinson's
disease (PD) is the second most common neurodegenerative disease among the
elderly, and it has been associated with both cognitive and postural
abnormalities such as Pisa syndrome (PS). Although its onset has been considered
to be multifactorial, the pathophysiological mechanisms underpinning PS are still
not fully explained. Until now, no study investigated the possible contribution
of cognitive dysfunction to occurrence of PS in PD. PATIENTS AND METHODS: Twenty
PD patients with PS and 20 PD patients without PS were enrolled. All patients
with PD underwent neuropsychological battery to assess behavioural disturbances,
memory, attention, frontal/executive and visuospatial functions. RESULTS: The two
groups did not differ on demographic features, age at PD onset and disease
duration, whereas they significantly differed on UPDRS-Part III, and levodopa
equivalent daily dose (LEDD). MANCOVA with above-mentioned clinical variable as
covariates revealed significant differences on tasks tapping verbal long-term
memory, and attentional and visuoperceptual abilities between groups. The binary
logistic regression revealed that higher LEDD and lower performance on
visuospatial task (Benton Judgment of Lines Orientation test) significantly
predicted occurrence of PS. CONCLUSION: Our results revealed a significant
association of PS with altered attention and visuoperceptual functions in PD,
suggesting that the occurrence of PS may be associated with alteration of both
frontal-striatal systems and posterior cortical areas.
PMID- 26427766
TI - The anti-dermatophyte activity of Commiphora molmol.
AB - CONTEXT: Commiphora molmol Engl (Burseraceae) or myrrh has been traditionally
used for the treatment of skin fungal infections. OBJECTIVE: This study evaluates
the antifungal activity of myrrh ethanol extract and essential oil against skin
dermatophytes. MATERIALS AND METHODS: The antifungal evaluations were performed
by the food poisoning technique (250 ppm) and micro-broth dilution assay (800
6.25 ug/mL) against Trichophyton rubrum, T. mentagrophytes, Microsporum canis, M.
gypseum, and T. verrucosum. The chemical composition of myrrh oil and ethanol
extract was analyzed by GC and GC-MS. RESULTS: Furanoeudesma 1,3-diene and
menthofuran were the main components of myrrh oil, while 2-tert-butyl-1,4
naphthoquinone, benzenemethanol,3-methoxy-alpha-phenyl, and curzerene were the
main components of myrrh ethanol extract. The inhibitory effect of myrrh oil and
ethanol extract against dermatophytes were 43.1-61.6% and 12.5-27.5%,
respectively. The MIC and MFC values of myrrh oil were 25-100 and 25-200 ug/mL
while these amounts for ethanol extract were 25-400 and 25-400 ug/mL,
respectively. Therefore, myrrh oil had higher antifungal activity than that of
the ethanol extract. Both extracts showed good anti-elastase activity.
CONCLUSION: The results of our investigation confirmed the traditional uses of C.
molmol as a poultice for the treatment of cutaneous fungal infections.
PMID- 26427767
TI - Striking Differences in Properties of Geometric Isomers of [Ir(tpy)(ppy)H](+):
Experimental and Computational Studies of their Hydricities, Interaction with
CO2, and Photochemistry.
AB - We prepared two geometric isomers of [Ir(tpy)(ppy)H](+), previously proposed as a
key intermediate in the photochemical reduction of CO2 to CO, and characterized
their notably different ground- and excited-state interactions with CO2 and their
hydricities using experimental and computational methods. Only one isomer, C
trans-[Ir(tpy)(ppy)H](+), reacts with CO2 to generate the formato complex in the
ground state, consistent with its calculated hydricity. Under photocatalytic
conditions in CH3CN/TEOA, a common reactive C-trans-[Ir(tpy)(ppy)](0) species,
irrespective of the starting isomer or monodentate ligand (such as hydride or
Cl), reacts with CO2 and produces CO with the same catalytic efficiency.
PMID- 26427769
TI - Functional Properties of Soybean and Processed Soy Foods Ingredients.
PMID- 26427770
TI - Feasibility of intercostal blood flow measurement by echo-Doppler technique in
healthy subjects.
AB - Intercostal artery blood flow supplies the external and internal intercostal
muscles, which are inspiratory and expiratory muscles. Intercostal blood flow
measured by the echo-Doppler (ED) technique has not previously been reported in
humans. This study describes the feasibility of this measurement during free and
loaded breathing in healthy subjects. Systolic, diastolic and mean blood flows
were measured in the eighth dorsal intercostal space during free and loaded
breathing using the ED technique. Flows were calculated as the product of the
artery intraluminal surface and blood velocity. Ten healthy subjects (42 +/- 13.6
years) were included. Integrated electromyogram (iEMG), arterial pressure,
cardiac frequency and breathing pattern were also recorded. Mean blood flows were
3.5 +/- 1.2 ml min-1 at rest, 6 +/- 2.6 ml min-1 while breathing through a
combined inspiratory and expiratory resistance and 4.0 +/- 1.3 ml min-1 1 min
after unloading. Diastolic blood flow was about one-third the systolic blood
flow. The changes in blood flows were consistent with those in iEMG. No change in
mean blood flow was observed between inspiration and expiration, suggesting a
balance in the perfusion of external and internal muscles during breathing. In
conclusion, ED is a feasible technique for non-invasive, real-time measurement of
intercostal blood flow in humans. In healthy subjects, mean blood flow appeared
tightly matched to iEMG activity. This technique may provide a way to assess the
vascular adaptations induced by diseases in which respiratory work is increased
or cardiac blood flow altered.
PMID- 26427771
TI - User-Friendly Platinum Catalysts for the Highly Stereoselective Hydrosilylation
of Alkynes and Alkenes.
AB - With a view to addressing the shortcomings of traditional catalysts, a new
generation of outstanding N-heterocyclic carbene platinum(0) complexes for the
hydrosilylation of unsaturated carbon-carbon bonds is reported. Their discovery
and application to the stereoselective addition of various silanes to silylated
alkynes, terminal acetylenes, and olefins is presented. Insights into the
catalytic cycle and the origin of the stereoselectivity are also discussed.
PMID- 26427772
TI - The Development of Faculty in Dental Education.
PMID- 26427773
TI - New Dental Accreditation Standard on Critical Thinking: A Call for Learning
Models, Outcomes, Assessments.
AB - This opinion article applauds the recent introduction of a new dental
accreditation standard addressing critical thinking and problem-solving, but
expresses a need for additional means for dental schools to demonstrate they are
meeting the new standard because articulated outcomes, learning models, and
assessments of competence are still being developed. Validated, research-based
learning models are needed to define reference points against which schools can
design and assess the education they provide to their students. This article
presents one possible learning model for this purpose and calls for national
experts from within and outside dental education to develop models that will help
schools define outcomes and assess performance in educating their students to
become practitioners who are effective critical thinkers and problem-solvers.
PMID- 26427774
TI - Social Media in the Dental School Environment, Part A: Benefits, Challenges, and
Recommendations for Use.
AB - Social media consist of powerful tools that impact not only communication but
relationships among people, thus posing an inherent challenge to the traditional
standards of who we are as dental educators and what we can expect of each other.
This article examines how the world of social media has changed dental education.
Its goal is to outline the complex issues that social media use presents for
academic dental institutions and to examine these issues from personal,
professional, and legal perspectives. After providing an update on social media,
the article considers the advantages and risks associated with the use of social
media at the interpersonal, professional, and institutional levels. Policies and
legal issues of which academic dental institutions need to be aware from a
compliance perspective are examined, along with considerations and resources
needed to develop effective social media policies. The challenge facing dental
educators is how to capitalize on the benefits that social media offer, while
minimizing risks and complying with the various forms of legal constraint.
PMID- 26427775
TI - Social Media in the Dental School Environment, Part B: Curricular Considerations.
AB - The goal of this article is to describe the broad curricular constructs
surrounding teaching and learning about social media in dental education. This
analysis takes into account timing, development, and assessment of the knowledge,
skills, attitudes, and behaviors needed to effectively use social media tools as
a contemporary dentist. Three developmental stages in a student's path to
becoming a competent professional are described: from undergraduate to dental
student, from the classroom and preclinical simulation laboratory to the clinical
setting, and from dental student to licensed practitioner. Considerations for
developing the dental curriculum and suggestions for effective instruction at
each stage are offered. In all three stages in the future dentist's evolution,
faculty members need to educate students about appropriate professional uses of
social media. Faculty members should provide instruction on the beneficial
aspects of this communication medium and help students recognize the potential
pitfalls associated with its use. The authors provide guidelines for customizing
instruction to complement each stage of development, recognizing that careful
timing is not only important for optimal learning but can prevent inappropriate
use of social media as students are introduced to novel situations.
PMID- 26427776
TI - Recruitment of Dental Hygiene Students from Underrepresented Minority Groups: A
National Survey of U.S. Dental Hygiene Programs.
AB - The aims of this study were to assess how U.S. undergraduate dental hygiene
programs recruit students, especially students from underrepresented minority
(URM) groups, and how the program directors value recruiting those students, how
satisfied they are with their efforts, which practices they use, and which
challenges they encounter. Relationships between diversity-related recruitment
motivation and satisfaction and the program and recruitment characteristics were
also explored. Survey data were collected from 56 of the 287 programs that could
be successfully contacted with individual emails to their directors (response
rate: 20%). The majority of responding programs recruited students into their
programs by using written materials (91%), websites (91%), on-campus events
(77%), and high school visits (52%). However, only 20% had written materials and
13% special events for recruiting students from URM groups. While 75% of the
responding program directors considered high grade point averages (GPAs) to be a
priority and 85% thought high GPAs were important/very important when recruiting
students, only 17% considered it a priority to recruit URM students, and only 35%
reported thinking it was important/very important to do so. The more of a
priority it was to have a diverse student body and the more important the
respondents considered it, the more likely they were to have written URM-specific
recruitment materials (r=0.34; p<0.05/r=0.39; p<0.01). The more the respondents
valued ACT scores, the less likely they were to engage in URM-specific
recruitment efforts (r=-0.38; p<0.05/r=-0.34; p<0.05). If the dental hygiene
profession is to better reflect the racial/ethnic makeup of the U.S. population,
dental hygiene programs' considerations and efforts related to the recruitment of
URM students need to be reconsidered.
PMID- 26427777
TI - Faculty Development at One Midwestern Dental School: A Program Evaluation.
AB - Most dental school faculty members arrive on campus with a wealth of clinical
experience but little to no teacher training. For the past two decades, there has
been a call for schools to educate their faculty on a wide variety of topics
including educational methodology and cutting-edge educational techniques through
faculty development programs. Drawing on theories of general program evaluation
as well as evaluation specific to educational programming, the aim of this study
was to investigate outcomes of the Faculty Development Program at the University
of Missouri-Kansas City School of Dentistry between 2007 and 2014. A mixed
methods research design gathered quantitative data via email survey sent to all
eligible teaching faculty members; it received an overall response rate of 54%
(N=51). Qualitative data came from open-ended survey questions and a focus group
with seven volunteer faculty participants. The survey data suggested that the
stated outcomes of faculty development were being met for all stakeholder groups
with varying degrees of success. Focus group results indicated a need for a more
formal new faculty orientation and better communication with all about the
specific charge of faculty development within the school. Evaluation of faculty
development activities in academic dental institutions is a necessary component
of the ongoing improvement of dental education. Suggestions for future
evaluations include the idea of collaborating with other dental schools to
increase sample sizes, which would increase participants' perception of the level
of confidentiality and make statistical analyses more robust.
PMID- 26427778
TI - Developing Dental Students' Awareness of Health Care Disparities and Desire to
Serve Vulnerable Populations Through Service-Learning.
AB - Service-learning in dental education helps students integrate knowledge with
practice in an underserved community setting. The aim of this study was to
explore how a service-learning experience affected a small group of dental
students' beliefs about cultural competence, professionalism, career development,
desire to practice in a community service setting, and perceptions about access
and disparities issues. Prior to beginning their first year of dental school,
five first-year dental students at one U.S. dental school participated in a six
week service-learning program in which they interned at one of three at-risk
settings in order to experience health care delivery there. After the program, 60
reflective writing assignments completed by the participants were analyzed using
grounded theory methods; interviews with the students were used to corroborate
the findings from that analysis. Seven themes identified in the journal
reflections and interview findings showed enhanced awareness of social health
care issues and patient differences, as well as a social justice orientation and
desire to address disparities. Building on this study, future research should
explore the curricular components of service-learning programs to ensure students
receive ample opportunity to reflect upon their experiences in order to integrate
previously held assumptions with their newfound knowledge.
PMID- 26427779
TI - Patients' Perceptions of Dehumanization of Patients in Dental School Settings:
Implications for Clinic Management and Curriculum Planning.
AB - Although the importance of empathy, rapport, and anxiety/pain awareness in
dentist-patient relations has been well documented, these factors continue to be
an issue with patients in many dental school clinics. The aim of this study was
to develop an in-depth understanding of how patients at an urban, university
affiliated medical center and its dental school's clinic experienced oral health
care and to generate ideas for improving the dental school's clinical curriculum
and management of the clinic. Although patient satisfaction surveys are common,
in-depth patient narratives are an underutilized resource for improving dental
education. In-depth qualitative interviews were conducted with 20 uninsured or
underinsured dental patients at these sites, and the results were analyzed using
content analysis. Major phenomena that participants discussed were the importance
of empathy and good rapport with their oral health providers and provider
awareness of dental pain and anxiety. Many patients also discussed feeling
dehumanized during dental visits. Based on their positive and negative
experiences, the participants made suggestions for how oral health professionals
can successfully engage patients in treatment.
PMID- 26427780
TI - Dental Students' Learning Experiences and Preferences Regarding Orofacial Pain: A
Cross-Sectional Study.
AB - Pain is a global health problem, the effects of which range from diminished
quality of life to pain management costs and loss of work and productivity. Pain
in the head and neck region is defined as a separate entity: orofacial pain
(OFP). However, some graduates from dental schools have reported feeling less
competent in their ability to diagnose OFP than in other areas of dentistry. The
aims of this study were to assess how students at one U.S. dental school had
learned about OFP and to identify the teaching methods and venues they would like
to see enhanced in the school's OFP curriculum. A cross-sectional four-question
survey was administered to 140 dental students in their third and fourth years;
the survey had a response rate of 53%. Most students reported having gained their
OFP knowledge mainly in dental school, and 91.9% selected didactic courses as the
main teaching method in which they had learned about this topic. Clinical
education was the main teaching venue these students said they would like to see
enhanced in order to gain more knowledge in most forms of OFP; this result
aligned with their learning preferences in general. These findings may help
dental schools design their OFP curricula to take account of students'
preferences as well as practical limitations regarding availability of clinical
experiences.
PMID- 26427781
TI - Establishing CAD/CAM in Preclinical Dental Education: Evaluation of a Hands-On
Module.
AB - The aim of this study was to evaluate a hands-on computer-assisted
design/computer-assisted manufacture (CAD/CAM) module in a preclinical dental
course in restorative dentistry. A controlled trial was conducted by dividing a
class of 56 third-year dental students in Germany into study and control groups;
allocation to the two groups depended on student schedules. Prior information
about CAD/CAM-based restorations was provided for all students by means of
lectures, preparation exercises, and production of gypsum casts of prepared resin
teeth. The study group (32 students) then participated in a hands-on CAD/CAM
module in small groups, digitizing their casts and designing zirconia frameworks
for single crowns. The digitization process was introduced to the control group
(24 students) solely by means of a video-supported lecture. To assess the
knowledge gained, a 20-question written examination was administered; 48 students
took the exam. The results were analyzed with Student's t-tests at a significance
level of 0.05. The results on the examination showed a significant difference
between the two groups: the mean scores were 16.8 (SD 1.7, range 13-19) for the
study group and 12.5 (SD 3, range 4-18) for the control group. After the control
group had also experienced the hands-on module, a total of 48 students from both
groups completed a questionnaire with 13 rating-scale and three open-ended
questions evaluating the module. Those results showed that the module was highly
regarded by the students. This study supports the idea that small-group hands-on
courses are helpful for instruction in digital restoration design. These
students' knowledge gained and satisfaction seemed to justify the time, effort,
and equipment needed.
PMID- 26427782
TI - Evidence Regarding Teaching and Assessment of Record-Keeping Skills in Training
of Dental Students.
AB - The aim of this study was to assess the literature on teaching and assessing
dental students' record-keeping skills prior to qualification to practice
independently as a dentist. A systematic literature review was performed using
Ovid MEDLINE and SCOPUS. Keywords used in the search included dental, record,
audit, education, and assessment. Electronic search results were screened for
publications that targeted undergraduate dental training, related to a record
keeping education intervention, and were published in English and available in
full text. Six studies met the inclusion and exclusion criteria. Data extraction
and quality assessment were performed, and research findings were compared across
the included studies. These six articles addressed the techniques used to teach
and assess record-keeping skills in a pre-qualification context. The techniques
included supervisor audits, peer audits, lectures, tutorials, research
assignments, case reports, record-keeping templates, and checklists of required
record components. The use of record audit as part of teaching and evaluation
dominated these articles; it was used as the assessment method in five of the six
studies. All methods of record-keeping training in studies published to date were
found effective in improving student record-keeping skills. However, there was
insufficient evidence to determine whether certain methods were more effective
than others.
PMID- 26427784
TI - Evaluation of new bone formation after sinus augmentation with two different
methods.
AB - The sinus infiltration technique for sinus floor elevation and simultaneous
implant placement has been used successfully when a reduced vertical height is
available in the posterior maxilla. However, the effect of the quantity of graft
material and the volume of the solution used on the volume of new bone formed has
not been fully investigated. The aim of this study was to evaluate, both
quantitatively and qualitatively, the new bone formation after sinus augmentation
using either the lateral sinus lift or sinus infiltration technique and to
determine any correlation with the volume of bone grafting material used.
Further, the volume of solution used in the sinus infiltration technique was also
assessed. Twenty healthy adults (13 women, seven men) were randomized to two
groups, each undergoing one of the two techniques. Quantitative aspects and the
space lifted in the sinus floor were analyzed using Simplant Pro Crystal
software. No correlation was found between the volume of bone created in the
sinus floor and the volume of bone grafting material used for the sinus
infiltration technique or the lateral sinus lift. A strong correlation was found
between the volume of liquid used in the sinus infiltration technique and the new
volume created in the sinus floor.
PMID- 26427785
TI - Cancer modelling in the NGS era - Part I: Emerging technology and initial
modelling.
AB - It is today indisputable that great progresses have been made in our molecular
understanding of cancer cells, but an effective implementation of such knowledge
into dramatic cancer-cures is still belated and yet desperately needed. This
review gives a snapshot at where we stand today in this search for cancer
understanding and definitive treatments, how far we have progressed and what are
the major obstacles we will have to overcome both technologically and for disease
modelling. In the first part, promising 3rd/4th Generation Sequencing
Technologies will be summarized (particularly IonTorrent and OxfordNanopore
technologies). Cancer modelling will be then reviewed from its origin in XIX
Century Germany to today's NGS applications for cancer understanding and
therapeutic interventions. Developments after Molecular Biology revolution (1953)
are discussed as successions of three phases. The first, PH1, labelled "Clonal
Outgrowth" (from 1960s to mid 1980s) was characterized by discoveries in
cytogenetics (Nowell, Rowley) and viral oncology (Dulbecco, Bishop, Varmus),
which demonstrated clonality. Treatments were consequently dominated by a
"cytotoxic eradication" strategy with chemotherapeutic agents. In PH2, (from the
mid 1980s to our days) the description of cancer as "Gene Networks" led to
targeted-gene-therapies (TGTs). TGTs are the focus of Section 3: in view of their
apparent failing (Ephemeral Therapies), alternative strategies will be discussed
in review part II (particularly cancer immunotherapy, CIT). Additional Pitfalls
impinge on the concepts of tumour heterogeneity (inter/intra; ITH). The described
pitfalls set the basis for a new phase, PH3, which is called "NGS Era" and will
be also discussed with ten emerging cancer models in the Review 2nd part.
PMID- 26427787
TI - Yiguanjian decoction and its ingredients inhibit angiogenesis in carbon
tetrachloride-induced cirrhosis mice.
AB - BACKGROUND: Cirrhosis is associated with angiogenesis and disruption of hepatic
vascular architecture. Yiguanjian (YGJ) decoction, a prescription from
traditional Chinese medicine, is widely used for treating liver diseases. We
studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and
explored possible mechanisms underlying this process. METHODS: Cirrhosis was
induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From
week 4 to week 6, cirrhotic mice were randomly divided into four groups:
sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum
biochemistries, hydroxyproline (Hyp) content and histopathological changes of
hepatic tissues were measured as were alpha-smooth muscle actin (alpha-SMA),
collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor
(VEGFR) 2 and hypoxia-inducible factor (HIF)-1alpha. RESULTS: Both YGJ and iYGJ
improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ
reduced hepatic tissue necroinflammatory and collagen fiber deposition in
cirrhosis mice. Compared to the CCl4 treated animals, Hyp, alpha-SMA, collagen I,
CD31, VEGF, VEGFR, and HIF-1alpha expression decreased in YGJ and iYGJ groups.
CONCLUSIONS: YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated
with CCl4 by inhibiting the HIF-1alpha/VEGF signaling pathway, suggesting that
anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic
hypoxic microenvironment.
PMID- 26427788
TI - Evaluating Nonattachment and Decentering as Possible Mediators of the Link
Between Mindfulness and Psychological Distress in a Nonclinical College Sample.
AB - Although increasing evidence shows that mindfulness is positively related to
mental health, the nature and mechanisms of this relationship are not fully
understood. Based on previous research findings and suggestions, the authors of
the current study hypothesized that decentering and nonattachment are 2 variables
that mediate the relationship between mindfulness and psychological distress. A
nonclinical, non-treatment-seeking sample of 308 students and employees from a
middle-class, primarily Caucasian university filled out mindfulness, decentering,
nonattachment, and mental distress measures online. Mediational analyses failed
to support the hypothesis. Results suggest that mindfulness and nonattachment are
independent predictors of nonclinical psychological distress and fully explain
the effect of decentering on psychological distress. Results should be
interpreted with caution and not generalized to clinical issues. A more
comprehensive look into the mechanisms of mindfulness, especially with rigorous
experimental, longitudinal studies, is warranted. The authors stress the
importance of checking alternative, equivalent models in mediation studies.
PMID- 26427786
TI - Structural Brain MRI Trait Polygenic Score Prediction of Cognitive Abilities.
AB - Structural brain magnetic resonance imaging (MRI) traits share part of their
genetic variance with cognitive traits. Here, we use genetic association results
from large meta-analytic studies of genome-wide association (GWA) for brain
infarcts (BI), white matter hyperintensities, intracranial, hippocampal, and
total brain volumes to estimate polygenic scores for these traits in three
Scottish samples: Generation Scotland: Scottish Family Health Study (GS:SFHS),
and the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921). These five
brain MRI trait polygenic scores were then used to: (1) predict corresponding MRI
traits in the LBC1936 (numbers ranged 573 to 630 across traits), and (2) predict
cognitive traits in all three cohorts (in 8,115-8,250 persons). In the LBC1936,
all MRI phenotypic traits were correlated with at least one cognitive measure,
and polygenic prediction of MRI traits was observed for intracranial volume. Meta
analysis of the correlations between MRI polygenic scores and cognitive traits
revealed a significant negative correlation (maximal r = 0.08) between the HV
polygenic score and measures of global cognitive ability collected in childhood
and in old age in the Lothian Birth Cohorts. The lack of association to a related
general cognitive measure when including the GS:SFHS points to either type 1
error or the importance of using prediction samples that closely match the
demographics of the GWA samples from which prediction is based. Ideally, these
analyses should be repeated in larger samples with data on both MRI and
cognition, and using MRI GWA results from even larger meta-analysis studies.
PMID- 26427790
TI - Evaluation of Anti-inflammatory and Some Possible Mechanisms of Antinociceptive
Effect of Ferula assa foetida Oleo Gum Resin.
AB - Asafetida is well known for its medicinal and therapeutic values in Iranian folk
medicine. This study was conducted to investigate the antinociceptive and anti
inflammatory effects of asafetida. In hot plate test, asafetida exhibited a
significant antinociceptive effect at all administered doses and the most
effective dose was 10 mg/kg. The highest maximum potent effect was observed 15
minutes after asafetida administration. The antinociceptive effect of asafetida
was not reversed by administration of any antagonist used in this study but
asafetida showed a remarkable antioxidant and also inhibitory action against
lipoxygenase activity. Paw weight was significantly reduced only in treated
animals with 2.5 mg/kg asafetida. Results clearly indicate that the asafetida
could be a potential source of anti-inflammatory and analgesic agent. These
effects may be due to its effective constituents such as monoterpenes, flavonoids
and phenolic components that have antioxidant properties and inhibit lipoxygenase
activity.
PMID- 26427789
TI - Topical use of Matricaria recutita L (Chamomile) Oil in the Treatment of
Monosymptomatic Enuresis in Children: A Double-Blind Randomized Controlled Trial.
AB - AIM: To evaluate the efficacy of topical use of Matricaria recutita L oil in the
treatment of enuresis in children. METHODS: Eighty patients diagnosed as
monosymptomatic nocturnal or daytime enuresis were allocated to receive
Matricaria recutita L (chamomile) oil or placebo topically for 6 weeks in a
double-blind randomized placebo-controlled trial with a parallel design. Patients
were evaluated prior to and following 8 weeks of the intervention in terms of
frequency of enuresis and any observed adverse events. RESULTS: The mean
frequency of enuresis at the first, second, and third 2 weeks was lower in the
intervention group compared with the placebo group, and the differences were
statistically significant (P < .001, P = .03, and P < .001, respectively). There
was no report of any adverse event in the study groups. CONCLUSION: The findings
of this study showed that the topical use of (chamomile) oil can decrease the
frequency of nocturia in children with monosymptomatic nocturnal or daytime
enuresis.
PMID- 26427791
TI - Physiopathology of Dementia in Iranian Traditional Medicine.
AB - Recently, an article published in this journal by Dr Seifaddini and colleagues.
In that article, the authors tried to connect dementia, including Alzheimer's
disease, with a condition mentioned in Iranian traditional medical condition,
Raoonat and Homgh In this condition, intellectual functions of the brain are
disturbed and therefore, learning and decision-making abilities are damaged. This
condition is not age limited and affects thinking ability but not memory. On the
other hand, there is a condition described in Iranian traditional medicine, which
completely matches with Alzheimer's disease. This condition is explained under
the title of Nesyan (forgetfulness). Nesyan has 5 subdivisions, one of which is
caused by the inclination of the brain normal temperament to more coldness and
dryness. By performing animal studies, we have recently shown that this kind of
Nesyan is related with Alzheimer's disease. Studies on the traditional
recommendations on treatment of this kind of Nesyan can be useful in treatment of
Alzheimer's disease.
PMID- 26427792
TI - The whole is greater than the sum of the parts: Distributed circuits in visual
cognition.
PMID- 26427793
TI - Fibronectin Splicing Variants Containing Extra Domain A Promote Atherosclerosis
in Mice Through Toll-Like Receptor 4.
AB - OBJECTIVE: Cellular fibronectin containing extra domain A (EDA(+)-FN) is abundant
in the arteries of patients with atherosclerosis. Several in vitro studies
suggest that EDA(+)-FN interacts with Toll-like receptor 4 (TLR4). We tested the
hypothesis that EDA(+)-FN exacerbates atherosclerosis through TLR4 in a
clinically relevant model of atherosclerosis, the apolipoprotein E-deficient
(Apoe(-/-)) mouse. APPROACH AND RESULTS: The extent of atherosclerosis was
evaluated in whole aortae and cross sections of the aortic sinus in male and
female EDA(-/-)Apoe(-/-) mice (which lack EDA(+)-FN), EDA(fl/fl)Apoe(-/-) mice
(which constitutively express EDA(+)-FN), and control Apoe(-/-) mice fed a high
fat Western diet for 14 weeks. Irrespective of sex, EDA(fl/fl)Apoe(-/-) mice
exhibited a 2-fold increase in atherosclerotic lesions (aorta and aortic sinus)
and macrophage content within plaques, whereas EDA(-/-)Apoe(-/-) mice exhibited
reduced atherosclerotic lesions (P<0.05 versus Apoe(-/-), n=10-12 mice/group),
although cholesterol and triglyceride levels and circulating leukocytes were
similar. Genetic ablation of TLR4 partially reversed atherosclerosis exacerbation
in EDA(fl/fl)Apoe(-/-) mice (P<0.05) but had no effect on atherosclerotic lesions
in EDA(-/-)Apoe(-/-) mice. Purified cellular FN, which contains EDA, potentiated
dose-dependent NFkappaB-mediated inflammation (increased phospho-NFkappaB
p65/NFkappaB p65, tumor necrosis factor-alpha, and interleukin-1beta) in bone
marrow-derived macrophages from EDA(-/-)Apoe(-/-) mice but not from EDA(-/-)TLR4(
/-)Apoe(-/-) mice. Finally, using immunohistochemistry, we provide evidence for
the first time that EDA(+)-FN colocalizes with macrophage TLR4 in murine aortic
lesions and human coronary artery atherosclerotic plaques. CONCLUSIONS: Our
findings reveal that TLR4 signaling contributes to EDA(+)-FN-mediated
exacerbation of atherosclerosis. We suggest that EDA(+)-FN could be a therapeutic
target in atherosclerosis.
PMID- 26427794
TI - Therapeutic Inhibition of miR-33 Promotes Fatty Acid Oxidation but Does Not
Ameliorate Metabolic Dysfunction in Diet-Induced Obesity.
AB - OBJECTIVE: miR-33 has emerged as an important regulator of lipid homeostasis.
Inhibition of miR-33 has been demonstrated as protective against atherosclerosis;
however, recent studies in mice suggest that miR-33 inhibition may have adverse
effects on lipid and insulin metabolism. Given the therapeutic interest in miR-33
inhibitors for treating atherosclerosis, we sought to test whether
pharmacologically inhibiting miR-33 at atheroprotective doses affected metabolic
parameters in a mouse model of diet-induced obesity. APPROACH AND RESULTS: High
fat diet (HFD) feeding in conjunction with treatment of male mice with 10 mg/kg
control anti-miR or anti-miR33 inhibitors for 20 weeks promoted equivalent weight
gain in all groups. miR-33 inhibitors increased plasma total cholesterol and
decreased serum triglycerides compared with control anti-miR, but not compared
with PBS-treated mice. Metrics of insulin resistance were not altered in anti
miR33-treated mice compared with controls; however, respiratory exchange ratio
was decreased in anti-miR33-treated mice. Hepatic expression of miR-33 targets
Abca1 and Hadhb were derepressed on miR-33 inhibition. In contrast, protein
levels of putative miR-33 target gene SREBP-1 or its downstream targets genes
Fasn and Acc were not altered in anti-miR33-treated mice, and hepatic lipid
accumulation did not differ between groups. In the adipose tissue, anti-miR33
treatment increased Ampk gene expression and markers of M2 macrophage
polarization. CONCLUSIONS: We demonstrate in a mouse model of diet-induced
obesity that therapeutic silencing of miR-33 may promote whole-body oxidative
metabolism but does not affect metabolic dysregulation. This suggests that
pharmacological inhibition of miR-33 at doses known to reduce atherosclerosis may
be a safe future therapeutic.
PMID- 26427795
TI - Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia.
AB - OBJECTIVE: Cyclic AMP responsive element-binding protein 3-like 3 (CREB3L3) is a
novel candidate gene for dominant hypertriglyceridemia. To date, only 4 kindred
with dominant hypertriglyceridemia have been found to be carriers of 2 nonsense
mutations in CREB3L3 gene (245fs and W46X). We investigated a family in which
hypertriglyceridemia displayed an autosomal dominant pattern of inheritance.
APPROACH AND RESULTS: The proband was a 49-year-old woman with high plasma
triglycerides (<=1300 mg/dL; 14.68 mmol/L). Her father had a history of moderate
hypertriglyceridemia, and her 51-year-old brother had triglycerides levels as
high as 1600 mg/dL (18.06 mmol/L). To identify the causal mutation in this
family, we analyzed the candidate genes of recessive and dominant forms of
primary hypertriglyceridemia by direct sequencing. The sequencing of CREB3L3 gene
led to the discovery of a novel minute frame shift mutation in exon 3 of CREB3L3
gene, predicted to result in the formation of a truncated protein devoid of
function (c.359delG-p.K120fsX20). Heterozygosity for the c.359delG mutation
resulted in a severe phenotype occurring later in life in the proband and her
brother and a good response to diet and a hypotriglyceridemic treatment. The same
mutation was detected in a 13-year-old daughter who to date is
normotriglyceridemic. CONCLUSIONS: We have identified a novel pathogenic mutation
in CREB3L3 gene in a family with dominant hypertriglyceridemia with a variable
pattern of penetrance.
PMID- 26427797
TI - A soluble cryogenic thermometer with high sensitivity based on excited-state
configuration transformations.
AB - Cryogenic temperature detection plays an irreplaceable role in exploring nature.
Developing high sensitivity, accurate, observable and convenient measurements of
cryogenic temperature is not only a challenge but also an opportunity for the
thermometer field. The small molecule 9-(9,9-dimethyl-9H-fluoren-3yl)-14-phenyl
9,14-dihydrodibenzo[a,c]phenazine (FIPAC) in 2-methyl-tetrahydrofuran (MeTHF)
solution is utilized for the detection of cryogenic temperature with a wide range
from 138 K to 343 K. This system possesses significantly high sensitivity at low
temperature, which reaches as high as 19.4% K(-1) at 138 K. The temperature
dependent ratio of the dual emission intensity can be fitted as a single
exponential curve as a function of temperature. This single-exponential curve can
be explained by the mechanism that the dual emission feature of FIPAC results
from the excited-state configuration transformations upon heating or cooling,
which is very different from the previously reported mechanisms. Here, our work
gives an overall interpretation for this mechanism. Therefore, application of
FIPAC as a cryogenic thermometer is experimentally and theoretically feasible.
PMID- 26427796
TI - Epac1 Deficiency Attenuated Vascular Smooth Muscle Cell Migration and Neointimal
Formation.
AB - OBJECTIVE: Vascular smooth muscle cell (SMC) migration causes neointima, which is
related to vascular remodeling after mechanical injury and atherosclerosis
development. We previously reported that an exchange protein activated by cAMP
(Epac) 1 was upregulated in mouse arterial neointima and promoted SMC migration.
In this study, we examined the molecular mechanisms of Epac1-induced SMC
migration and the effect of Epac1 deficiency on vascular remodeling in vivo.
APPROACH AND RESULTS: Platelet-derived growth factor-BB promoted a 2-fold
increase in SMC migration in a primary culture of aortic SMCs obtained from
Epac1(+/+) mice (Epac1(+/+)-ASMCs), whereas there was only a 1.2-fold increase in
Epac1(-/-)-ASMCs. The degree of platelet-derived growth factor-BB-induced
increase in intracellular Ca(2+) was smaller in Fura2-labeled Epac1(-/-)-ASMCs
than in Epac1(+/+)-ASMCs. In Epac1(+/+)-ASMCs, an Epac-selective cAMP analog or
platelet-derived growth factor-BB increased lamellipodia accompanied by cofilin
dephosphorylation, which is induced by Ca(2+) signaling, whereas these effects
were rarely observed in Epac1(-/-)-ASMCs. Furthermore, 4 weeks after femoral
artery injury, prominent neointima were formed in Epac1(+/+) mice, whereas
neointima formation was significantly attenuated in Epac1(-/-) mice in which
dephosphorylation of cofilin was inhibited. The chimeric mice generated by bone
marrow cell transplantation from Epac1(+/+) into Epac1(-/-) mice and vice versa
demonstrated that the genetic background of vascular tissues, including SMCs
rather than of bone marrow-derived cells affected Epac1-mediated neointima
formation. CONCLUSIONS: These data suggest that Epac1 deficiency attenuates
neointima formation through, at least in part, inhibition of SMC migration, in
which a decrease in Ca(2+) influx and a suppression of cofilin-mediated
lamellipodia formation occur.
PMID- 26427798
TI - Predictors of non-adherence to antihypertensive medication in Kinshasa,
Democratic Republic of Congo: a cross-sectional study.
AB - BACKGROUND: Hypertension remains a public health challenge worldwide. In the
Democratic Republic of Congo, its prevalence has increased in the past three
decades. Higher prevalence of poor blood pressure control and an increasing
number of reported cases of complications due to hypertension have also been
observed. It is well established that non-adherence to antihypertensive
medication contributes to poor control of blood pressure. The aim of this study
is to measure non-adherence to antihypertensive medication and to identify its
predictors. METHODS: A cross-sectional study was conducted at Kinshasa Primary
Health-care network facilities from October to November 2013. A total of 395
hypertensive patients were included in the study. A structured interview was used
to collect data. Adherence to medication was assessed using the Morisky
Medication Scale. Covariates were defined according to the framework of the World
Health Organization. Logistic regression was used to identify predictors of non
adherence. RESULTS: A total of 395 patients participated in this study. The
prevalence of non-adherence to antihypertensive medication and blood pressure
control was 54.2 % (95 % CI 47.3-61.8) and 15.6 % (95 % CI 12.1-20.0),
respectively. Poor knowledge of complications of hypertension (OR = 2.4; 95 % CI
1.4-4.4), unavailability of antihypertensive drugs in the healthcare facilities
(OR = 2.8; 95 % CI 1.4-5.5), lack of hypertensive patients education in the
healthcare facilities (OR = 1.7; 95 % CI 1.1-2.7), prior experience of medication
side effects (OR = 2.2; 95 % CI 1.4-3.3), uncontrolled blood pressure (OR = 2.0;
95 % CI 1.1-3.9), and taking non-prescribed medications (OR = 2.2; 95 % CI 1.2
3.8) were associated with non-adherence to antihypertensive medication.
CONCLUSION: This study identified predictors of non-adherence to antihypertensive
medication. All predictors identified were modifiable. Interventional studies
targeting these predictors for improving adherence are needed.
PMID- 26427799
TI - Nutritional epigenetics with a focus on amino acids: implications for the
development and treatment of metabolic syndrome.
AB - Recent findings from human and animal studies indicate that maternal
undernutrition or overnutrition affects covalent modifications of the fetal
genome and its associated histones that can be carried forward to subsequent
generations. An adverse outcome of maternal malnutrition is the development of
metabolic syndrome, which is defined as a cluster of disorders including obesity,
hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertension and insulin
resistance. The transgenerational impacts of maternal nutrition are known as
fetal programming, which is mediated by stable and heritable alterations of gene
expression through covalent modifications of DNA and histones without changes in
DNA sequences (namely, epigenetics). The underlying mechanisms include chromatin
remodeling, DNA methylation (occurring at the 5'-position of cytosine residues
within CpG dinucleotides), histone modifications (acetylation, methylation,
phosphorylation, ubiquitination and sumoylation) and expression and activity of
small noncoding RNAs. The enzymes catalyzing these reactions include S
adenosylmethionine-dependent DNA and protein methyltransferases, DNA
demethylases, histone acetylase (lysine acetyltransferase), general control
nonderepressible 5 (GCN5)-related N-acetyltransferase (a superfamily of
acetyltransferase) and histone deacetylase. Amino acids (e.g., glycine,
histidine, methionine and serine) and vitamins (B6, B12 and folate) play key
roles in provision of methyl donors for DNA and protein methylation. Therefore,
these nutrients and related metabolic pathways are of interest in dietary
treatment of metabolic syndrome. Intervention strategies include targeting
epigenetically disturbed metabolic pathways through dietary supplementation with
nutrients (particularly functional amino acids and vitamins) to regulate one
carbon-unit metabolism, antioxidative reactions and gene expression, as well as
protein methylation and acetylation. These mechanism-based approaches may
effectively improve health and well-being of affected offspring.
PMID- 26427800
TI - A cell-targeted chemotherapeutic nanomedicine strategy for oral squamous cell
carcinoma therapy.
AB - BACKGROUND: Oral squamous cell carcinoma (OSCC) or cancers of oral cavity is one
of the most common cancers worldwide with high rate of mortality and morbidity.
At present, chemotherapy is one of the most effective treatments; however it
often fails to meet the requirements in the clinical therapy. In the present
study, we have successfully formulated ligand-decorated cancer-targeted CDDP
loaded PLGA-PEG/NR7 nanoparticles and demonstrated the feasibility of using NR7
peptide for targeted delivery, rapid intracellular uptake, and enhanced cytotoxic
effect in receptor-overexpressed OSCC cancer cells. RESULTS: Nanosized particles
were formed and sustained release patterns were observed for PLGA/NR7
nanoparticles. Significantly higher cellular uptake was observed in HN6 OSCC
cancer cells and superior anticancer effects are observed from the optimized
targeted nanoparticles. Furthermore, Live/Dead assay showed a higher extent of
red fluorescence was observed for the cells exposed with PLGA/NR7 than compared
with non-targeted PLGA NP. The presence of the NR7-targeting moiety on the
surface of PLGA carriers could allow the specific receptor-mediated
internalization, enhanced cellular uptake, and higher cell killing potency.
Especially, PLGA/NR7 NP exhibited a superior apoptosis effect in HN6 cancer cells
with around ~45 % (early and late apoptotic stage) and ~59 % after 24 and 48 h
incubation, respectively. It is apparent that the actively targeted micelles will
deliver more anticancer agent to cancer cell than non-targeted one. CONCLUSION:
Altogether, our results show the feasibility and promise of a cell-targeted
anticancer nanomedicine strategy that can be effective for the treatment of oral
squamous cell carcinoma. The present work might be of great importance to the
further exploration of the potential application of PLGA/NR7 in the clinically
relevant animal models.
PMID- 26427801
TI - Prognostic impact of decisions taken by the heart team in patients evaluated for
transcatheter aortic valve implantation.
AB - OBJECTIVE: To analyze long-term survival and predictors of mortality in patients
evaluated for transcatheter aortic valve implantation (TAVI) depending on the
decision taken by the heart team. METHODS: All patients with severe aortic
stenosis and high surgical risk evaluated for TAVI between June 2008 and June
2012 were included. Patients were grouped according to the therapeutic strategy
decided by the heart team. Mean follow-up was 16.6 months (maximum 55.3).
RESULTS: A total of 149 patients were evaluated: 79 were accepted for TAVI, 12
had no current indication for valve replacement and were deferred, 13 were
redirected to conventional surgery and 45 received medical treatment. The
evaluated patients had a mean age of 83.7 years and a mean EuroSCORE of 19.8+/
12.3. Median survival free from all-cause death was 34.7 months (95% CI 27.1
42.3) in the TAVI group, 47.4 months (95% CI 0-97.4) in the deferred intervention
group, not available in the surgery group and 8.2 months (95% CI 5.6-10.9) in the
medical treatment group (log-rank p<0.001). After multivariable adjustment, only
treatment group remained as an independent predictor of mortality. Considering
the TAVI group as the reference category, the adjusted hazard ratio for all-cause
death was 0.70 (95% CI 0.24-2.04) for the deferred intervention group, 0.16 (95%
CI 0.02-1.19) for the surgery group and 2.47 (95% CI 1.46-4.18) for the medical
treatment group. CONCLUSION: The decision taken by the heart team on potential
candidates for TAVI has a decisive prognostic significance, as those who are
unsuitable for any kind of valve replacement have a significantly higher
mortality.
PMID- 26427802
TI - Anemia and iron in heart failure--a brief comment.
PMID- 26427803
TI - The temperament and character personality profile of the glaucoma patient.
AB - BACKGROUND: To determine the temperament and character profile of glaucoma
patients. METHODS: A total of 234 patients (104 with primary open angle glaucoma,
and 130 control subjects without any ocular disease) were selected for this
prospective, cross-sectional study. All the participants underwent a
comprehensive ophthalmological examination, including the best corrected visual
acuity, intraocular pressure measurement, gonioscopy, and visual field analysis.
All the participants were given the Turkish version of the Temperament and
Character Inventory (TCI). The TCI is a self-reported evaluate, with 240
true/false items measuring four domains of temperament; harm avoidance (HA),
persistence (PS), novelty seeking (NS), reward dependence (RD), and three domains
of character; self-transcendence (ST), cooperativeness (C), self-directedness
(SD). RESULTS: The glaucoma patients achieved the higher scores than the controls
for the HA and SD dimensions (p < 0.001 and p = 0.033). The glaucoma patients
scored lower than the controls for the NS, P and ST dimensions (p < 0.001, p <
0.001 and p = 0.002). There were no differences in the RD and C scores between
the patients and the controls (p = 0.944 and p = 0.343). There was no correlation
between the duration of illness and the TCI dimensions. Disease severity was
positively associated with HA (r = 0,220, p = 0,025) and the anticipatory worry
(r = 0.227, p = 0.021) dimension. CONCLUSIONS: Glaucoma patients had a different
personality profile to healthy individuals. This may affect treatment compliance
and is also important when coping with maladaptive patient attitudes.
PMID- 26427804
TI - A phantom assessment of achievable contouring concordance across multiple
treatment planning systems.
AB - In this paper, the highest level of inter- and intra-observer conformity
achievable with different treatment planning systems (TPSs), contouring tools,
shapes, and sites have been established for metrics including the Dice similarity
coefficient (DICE) and Hausdorff Distance. High conformity values, e.g.
DICE(Breast_Shape)=0.99+/-0.01, were achieved. Decreasing image resolution
decreased contouring conformity.
PMID- 26427805
TI - Mature results from a Swedish comparison study of conventional versus accelerated
radiotherapy in head and neck squamous cell carcinoma - The ARTSCAN trial.
AB - BACKGROUND AND PURPOSE: This report contains the mature five-year data from the
Swedish ARTSCAN trial including information on the influence of p16 positivity
(p16+) for oropharyngeal cancers. MATERIAL AND METHODS: Patients with previously
untreated squamous cell carcinoma without distant metastases of the oral cavity,
oropharynx, larynx (except T1-2, N0 glottic cancers) and hypopharynx were
included. Patients were randomised between accelerated fractionation (AF)
(1.1Gy+2Gy per day, 5days/week for 4.5weeks, total dose 68Gy) and conventional
fractionation (CF) (2Gy per day, 5days/week for 7weeks, total dose 68Gy). Human
papillomavirus (HPV)-associated p16-expression was assessed retrospectively in
tumour tissues from patients with oropharyngeal carcinoma. RESULTS: There was no
significant difference in loco-regional control (LRC) between AF and CF (log-rank
test p=0.75). LRC at 5years was 65.5% for AF and 64.9% for CF. Overall survival
(OS) was similar in both arms (p=0.99). The estimated cancer specific survival
(CSS) at 5years was 62.2% (AF) and 63.3% (CF) (p=0.99). 206 specimens were
analysed for p16 with 153 specimens (74%) identified as p16+. P16 status did not
discriminate for response to AF vs. CF with regard to LRC, OS or CSS. Patients
with p16+ tumours had a statistically significant better overall prognosis
compared with p16- tumours. CONCLUSION: This update confirms the results of the 2
year report. We failed to identify a positive effect resulting from AF with
regards to LRC, OS and CSS. The addition of information on the HPV-associated p16
overexpression did not explain this lack of effect.
PMID- 26427807
TI - Is "Good Neurologic Outcome" Following Cardiac Arrest Good Enough?
PMID- 26427806
TI - Prognosis of sepsis induced by cecal ligation and puncture in mice improved by
anti-Clonorchis Sinensis cyclopholin a antibodies.
AB - BACKGROUND: Cyclophilin A (CyPA), a ubiquitously distributed intracellular
protein, is thought to be one of the important inflammatory factors and plays a
significant role in the development process of sepsis. In the form of cytokine,
CyPA deteriorates sepsis by promoting intercellular communication, apoptosis of
endothelial cells and chemotactic effect on inflammatory cells. In our previous
study, cyclophilin A of Clonorchis sinensis (CsCyPA), a type of excretory
secretory antigen, could induce the patients infected with Clonorchis sinensis to
produce specific anti-CsCyPA antibodies. In this study, we investigated whether
anti-CsCyPA antibodies could cross-react with CyPA and then play a protective
role against sepsis, just like other anti-cytokine antagonists. METHODS: The mice
model with sepsis was established with cecal ligation and puncture (CLP). Fifty
mg/kg purified anti-CsCyPA antibodies were injected via the caudal vein 6 h after
the CLP operation, and persistent observation was performed for 72 h. Blood
samples and tissues were collected at 6 h, 12 h, 24 h, 48 h and 72 h after CLP.
Cytokines in serum were measured by ELISA. Lung and mesentery tissues were
stained with hematoxylin-eosin. Endothelial cells (ECs) isolated from murine
aorta were co-cultured with CyPA of mice (MuCyPA) and anti-CsCyPAs for 24 h,
then, viability was measured by Cell Counting Kit-8. RESULTS: Anti-CsCyPA
antibodies could combine with MuCyPA and inhibit its peptidyl prolyl isomerase
(PPIase) activity. In the antibodies treatment group, blood coagulation
indicators including PT, aPTT, D-dimer and platelet count were obviously more
ameliorative, the proinflammary factors like IL-6, TNF-alpha, IL-1beta were
significantly lower at 12 h and 24 h after surgery and the viability of ECs was
significantly improved compared to those in the control group. Furthermore, the
survival rate was elevated, ranging from 10.0 % to 45.0 % compared to the control
group. CONCLUSIONS: These antibodies may have a favorable effect on sepsis via
inhibition of enzymic activity or protection of endothelial cells.
PMID- 26427808
TI - Pediatric Acute Kidney Injury-Deadly Now, Costly Later, and a Public Health
Burden.
PMID- 26427809
TI - Critical Care Transport: How Do We Measure Up?
PMID- 26427810
TI - Under Pressure: Defining Management Goals for Pediatric Traumatic Brain Injury.
PMID- 26427811
TI - Pediatric Out-of-Hospital Cardiac Arrest Outcomes: A Case of Male/Female
Inequality?
PMID- 26427812
TI - Family-Centered Care in the PICU: Where Do We Go From Here?
PMID- 26427813
TI - Is It Safe? Are There Limits With Procedural Sedation for Endoscopy in Children?
PMID- 26427814
TI - Who Should Perform Critical Procedures on Children Prehospital, and How Often?
PMID- 26427815
TI - Early Enteral Nutrition in the PICU: Should We Trust Our Gut?
PMID- 26427816
TI - Fluid Resuscitation in Pediatric Sepsis: Lack of Data Versus Lack of Equipoise.
PMID- 26427817
TI - A Changing Workforce for the Changing Needs of Critically Ill Children in the
United States and Canada.
PMID- 26427818
TI - It's About Time ....
PMID- 26427819
TI - Standardizing the Postoperative Handover Process in the PICU.
PMID- 26427820
TI - The authors reply.
PMID- 26427821
TI - Is It Time for Food of the Soul in Pediatric Critical Care?
PMID- 26427822
TI - The authors reply.
PMID- 26427823
TI - Motivational strategies for returning patients with low back pain to usual
activities: A survey of physiotherapists working in Australia.
AB - Timely resumption of usual activities is integral to successful functional
outcomes in individuals with low back pain (LBP). Little is known about how
physiotherapists motivate their patients achieve this. This study examined
physiotherapists' knowledge, reported usage and training in a set of 12
motivational strategies. The results of an online cross sectional survey of 170
Australian physiotherapists were compared descriptively, and potential
associations between therapist training and strategy use, confidence and
perceived effectiveness analysed. Participants considered it extremely important
to motivate individuals with LBP to return to usual activities and most commonly
reported managing this aspect of treatment exclusively. Active goal setting was
the most recognised motivational strategy and transtheoretical based counselling
the least recognised. Provision of verbal information and praise/encouragement
were reported as the most frequently used strategies. The most common reasons for
not using a familiar motivational strategy were time constraints and lack of
training. Training in active goal setting was associated with greater use,
confidence and perceived effectiveness and was most commonly perceived as
moderately effective. Cognitive behavioural therapy was well recognised and
training associated with greater use and confidence but not perceived
effectiveness. Motivational interviewing was known to approximately half of
respondents, consistent with its infancy in LBP and training was not associated
with use, confidence or perceived effectiveness. Further research into clearly
defined, time efficient and physiotherapy specific motivational interventions for
individuals ambivalent to returning to usual activities following an episode of
low back pain, may help address the issues identified by the current survey.
PMID- 26427824
TI - Osteopathic educators' attitudes towards osteopathic principles and their
application in clinical practice: A qualitative inquiry.
AB - RATIONALE: The implicit use of overarching osteopathic principles (OP) in
clinical practice is a regulatory requirement; agreed definition of what
constitutes such principles remains elusive. The profession currently faces
questions of identity and relevance in the face of evidence-informed healthcare.
OBJECTIVE: This study sought to investigate the opinions and experiences of
practising osteopathic educators as to how OP are relevant to clinical practice
in isolation and to the profession as a whole. DESIGN: A qualitative approach
employing grounded theory to explore the views of current practitioners involved
in osteopathic education. SUBJECTS: Nine practising osteopaths were selected for
the study using initially purposive then theoretical sampling. METHODOLOGY: Semi
structured interviews were used to gather data, audio-recorded, transcribed
verbatim and anonymised. Data was analysed and interpreted using a thematic
framework approach and conceptually modelled. Triangulation was completed; peer
corroboration for high-level themes and participant confirmation for transcript
authenticity was obtained. RESULTS: Two polarised concepts emerged: (1) OP
benefit the profession and (2) OP limit or jeopardize the profession. These
emanated from different perceptions of the identity of osteopathy: (1) osteopathy
as a philosophy or (2) osteopathy as a manual therapy with a philosophical
background. CONCLUSION: The osteopathic profession faces the danger of being
divided on the basis of ideological differences from within. The increasing
criticality applied to UK healthcare behoves the osteopathic profession to
clarify its aims, guiding 'principles' and underlying values. This could be
problematic in light of the divergence of views, leading to a situation of either
settling these differences or irrevocably fracturing the profession.
PMID- 26427825
TI - Clarifying phylogenetic relationships and the evolutionary history of the bivalve
order Arcida (Mollusca: Bivalvia: Pteriomorphia).
AB - The systematics of the bivalve order Arcida constitutes an unresolved conundrum
in bivalve systematics. The current definition of Arcida encompasses two
superfamilies: Limopsoidea, which includes the recent families Philobryidae and
Limopsidae, and Arcoidea, which encompasses the families Arcidae, Cucullaeidae,
Noetiidae, Glycymerididae and Parallelodontidae. This classification, however, is
controversial particularly with respect to the position and taxonomic status of
Glycymerididae. Previous molecular phylogenies were limited either by the use of
only a single molecular marker or by including only a few limopsoid and
glycymeridid taxa. The challenging nature of Arcida taxonomy and the
controversial results of some of the previous studies, prompted us to use a broad
range of taxa (55 species), three nuclear markers (18S rRNA, 28S rRNA and histone
H3) and a wide range of algorithmic approaches. This broad but stringent approach
led to a number of results that differ significantly from previous studies. We
provide the first molecular evidence that supports the separation of Arcoidea
from Limopsoidea, although the exact position of Glycymerididae remains
unresolved, and the monophyly of Limopsoidea is algorithm-dependent. In addition,
we present the first time-calibrated evolutionary tree of Arcida relationships,
indicating a significant increase in the diversification of arcidan lineages at
the beginning of the Cretaceous, around 140Ma. The monophyly of Arcida, which has
been supported previously, was confirmed in all our analyses. Although
relationships among families remain somehow unresolved we found support for the
monophyly of most arcidan families, at least under some analytical conditions
(i.e., Glycymerididae, Noetiidae, Philobryidae, and Limopsidae). However,
Arcidae, and particularly Arcinae, remain a major source of inconsistency in the
current system of Arcida classification and are in dire need of taxonomic
revision.
PMID- 26427826
TI - Inactivation of human pathogenic dermatophytes by non-thermal plasma.
AB - Non-thermal plasma (NTP) was tested as an in vitro deactivation method on four
human pathogenic dermatophytes belonging to all ecological groups including
anthropophilic Trichophyton rubrum and Trichophyton interdigitale, zoophilic
Arthroderma benhamiae, and geophilic Microsporum gypseum. The identification of
all strains was confirmed by sequencing of ITS rDNA region (internal transcribed
spacer region of ribosomal DNA). Dermatophyte spores were suspended in water or
inoculated on agar plates and exposed to NTP generated by a positive or negative
corona discharge, or cometary discharge. After 15 min of exposure to NTP a
significant decrease in the number of surviving spores in water suspensions was
observed in all species. Complete spore inactivation and thus decontamination was
observed in anthropophilic species after 25 min of exposure. Similarly, a
significant decrease in the number of surviving spores was observed after 10-15
min of exposure to NTP on the surface of agar plates with full inhibition after
25 min in all tested species except of M. gypseum. Although the sensitivity of
dermatophytes to the action of NTP appears to be lower than that of bacteria and
yeast, our results suggest that NTP has the potential to be used as an
alternative treatment strategy for dermatophytosis and could be useful for
surface decontamination in clinical practice.
PMID- 26427827
TI - Flavin mononucleotide (FMN)-based fluorescent protein (FbFP) as reporter for
promoter screening in Clostridium cellulolyticum.
AB - Conventional methods for screening promoters in anaerobic bacteria are generally
based on detection of enzymatic reactions and thus usually complicated or strain
specific. Therefore a more efficient and universal method will be valuable. Here,
using cellulolytic bacteria Clostridium cellulolyticum H10 as a model, we
employed an oxygen-independent flavin-based fluorescent protein (FbFP) derived
from Pseudomonas putida as a quantitative reporter for the screening of promoter
via monitoring fluorescence intensity. The stability and reliability of FbFP
fluorescence were proven by the high correlation (R(2)=0.87) between fluorescence
intensity and abundance of FbFP. Moreover, two endogenous promoters with
exceptional performance were identified and characterized, including a
constitutive promoter p3398 and an inducible promoter p1133. Compared to the
existing reporter systems widely used in clostridia, this FbFP-based method is
more rapid, intuitive and versatile, and the endogenous promoters reported here
should enrich the synthetic biology toolbox for this and related organisms.
PMID- 26427828
TI - Usefulness of Pseudocontinuous Arterial Spin-Labeling for the Assessment of
Patients with Head and Neck Squamous Cell Carcinoma by Measuring Tumor Blood Flow
in the Pretreatment and Early Treatment Period.
AB - BACKGROUND AND PURPOSE: For the assessment of the treatment response in non
surgical treatment, tumor blood flow provides the functional information of the
tumor which is different from the morphological information such as tumor volume.
The purpose of this study was to evaluate the diagnostic value of tumor blood
flow values obtained by pseudocontinuous arterial spin-labeling in patients with
head and neck squamous cell carcinoma. MATERIALS AND METHODS: Forty-one patients
with head and neck squamous cell carcinoma were evaluated by using
pseudocontinuous arterial spin-labeling. Quantitative tumor blood flow was
calculated at the pretreatment and the early treatment periods in all the
patients, and the percentage change of tumor blood flow between the two was
calculated. At the early treatment period, based on their tumor volume reduction
rate, we divided the patients into stable disease and partial response groups for
a subgroup analysis. The local control or failure was confirmed either by
histopathology or by radiologic evaluation within the follow-up. RESULTS:
Pretreatment tumor blood flow in patients in the failure group was significantly
lower than that in patients in the local control group. In the subgroup analysis
of patients with stable disease, the percentage change of tumor blood flow was
significantly larger (due to the tumor blood flow increase from pretreatment
value) in the local control group than in the failure group. In addition, in
patients with a partial response, the percentage change of tumor blood flow was
significantly smaller (due to the tumor blood flow decrease from the pretreatment
value) in the local control group than in the failure group. The accuracy for
determination of the local control group or the failure group in pretreatment
tumor blood flow was 0.83 and that in the combination use of the percentage
change of tumor blood flow and tumor volume in the early treatment period was
0.93. CONCLUSIONS: Tumor blood flow obtained by pseudocontinuous arterial spin
labeling can be useful for the determination of local control. The combined use
of the percentage change of tumor blood flow and tumor volume had particularly
high diagnostic accuracy.
PMID- 26427829
TI - Posterior Inferior Cerebellar Artery Patency after Flow-Diverting Stent
Treatment.
AB - BACKGROUND AND PURPOSE: The rate of PICA occlusion after flow-diverting stent
placement for vertebral and vertebrobasilar artery aneurysms is not known. The
purpose of this study is to determine the medium-term rate of PICA patency and
risk factors for occlusion after such aneurysm treatment. MATERIALS AND METHODS:
Patients were identified who had vertebral or vertebrobasilar artery aneurysms
and who were treated by placing a flow-diverting stent across the PICA ostium.
Demographic and procedural factors associated with stent placement were recorded.
Patency of the PICA was evaluated immediately after stent placement and on follow
up angiography. RESULTS: Thirteen patients with vertebral or vertebrobasilar
artery aneurysms were treated in the study period, of whom 4 presented with
subarachnoid hemorrhage. The average number of devices that spanned the PICA
ostium was 1.77 (range, 1-3), with no immediate PICA occlusions. There were no
postoperative strokes in the treated PICA territory, although there was 1
contralateral PICA-territory stroke of unclear etiology without clinical
sequelae. In 11 patients with follow-up angiography at a mean of 10.6 months
(range, 0.67-27.9 months), the PICA patency rate remained 100%. CONCLUSIONS: Flow
diverting stent placement across the PICA ostium in the treatment of vertebral
and vertebrobasilar artery aneurysms may not result in immediate or midterm PICA
occlusion.
PMID- 26427830
TI - Ipilimumab Therapy for Melanoma: A Mimic of Leptomeningeal Metastases.
PMID- 26427831
TI - Multimodal Diagnostic Imaging for Hyperacute Stroke.
AB - In April 2015, the American Roentgen Ray Society and the American Society of
Neuroradiology cosponsored a unique program designed to evaluate the state of the
art in the imaging work-up of acute stroke. This topic has grown in importance
because of the recent randomized controlled trials demonstrating the clear
efficacy of endovascular stroke treatment. The authors, who were participants in
that symposium, will highlight the points of emphasis in this article.
PMID- 26427832
TI - Diagnostic Accuracy of PET, SPECT, and Arterial Spin-Labeling in Differentiating
Tumor Recurrence from Necrosis in Cerebral Metastasis after Stereotactic
Radiosurgery.
AB - BACKGROUND AND PURPOSE: Radiographic assessment of cerebral metastasis after
stereotactic radiosurgery remains a major challenge in neuro-oncology. It is
often difficult to distinguish tumor progression from radiation necrosis in this
setting using conventional MR imaging. The objective of this study was to compare
the diagnostic sensitivity and specificity of different functional imaging
modalities for detecting tumor recurrence after stereotactic radiosurgery.
MATERIALS AND METHODS: We retrospectively reviewed patients treated between 2007
and 2010 and identified 14 patients with cerebral metastasis who had clinical or
radiographic progression following stereotactic radiosurgery and were imaged with
arterial spin-labeling, FDG-PET, and thallium SPECT before stereotactic biopsy.
Diagnostic accuracy, specificity, sensitivity, positive predictive value, and
negative predictive value were calculated for each imaging technique by using the
pathologic diagnosis as the criterion standard. RESULTS: Six patients (42%) had
tumor progression, while 8 (58%) developed radiation necrosis. FDG-PET and
arterial spin-labeling were equally sensitive in detecting tumor progression
(83%). However, the specificity of arterial spin-labeling was superior to that of
the other modalities (100%, 75%, and 50%, respectively). A combination of
modalities did not augment the sensitivity, specificity, positive predictive
value, or negative predictive value of arterial spin-labeling. CONCLUSIONS: In
our series, arterial spin-labeling positivity was closely associated with the
pathologic diagnosis of tumor progression after stereotactic radiosurgery.
Validation of this finding in a large series is warranted.
PMID- 26427833
TI - On the Use of DSC-MRI for Measuring Vascular Permeability.
AB - BACKGROUND AND PURPOSE: Contrast agent extravasation has been shown to confound
brain tumor perfusion measurements with DSC-MR imaging, necessitating the use of
correction techniques (eg, Weisskoff, Bjornerud). Leakage parameters (K2 and
K(a)) postulated to reflect vessel permeability can be extracted from these
correction methods; however, the biophysical interpretation of these parameters
and their relationship to commonly used MR imaging measures of vascular
permeability (eg, contrast agent volume transfer constant, [K(trans)]) remain
unclear. Given that vascular density, as assessed by blood volume, and vascular
permeability, as reflected by K(trans) (and potentially K2 or K(a)), report on
unique and clinically informative vascular characteristics, there is a compelling
interest to simultaneously assess these features. MATERIALS AND METHODS: We
acquired multiecho DSC-MR imaging data, allowing the simultaneous computation and
voxelwise comparison of single- and dual-echo derived measures of K2, K(a) and
K(trans) in patients with glioma. This acquisition enabled the investigation of
competing T1 and T2* leakage effects and TE dependency on these parameters.
RESULTS: K2 and K(a) displayed nonsignificant (P = .150 and P = .060,
respectively) voxelwise linear correlations with K(trans), while a significant (P
< .001) inverse relationship was observed between K2 and Ka (coefficient of
determination [r(2)] = 0.466-0.984). Significantly different (P < .005) mean
estimates were found between voxels exhibiting predominately T1 and T2* effects
for K2 and K(a). K(trans), however, was observed to be similar between these
voxels (0.109 versus 0.092 minutes(-1)). Significant differences (P < .001) in
extracellular-extravascular volume fraction (v(e)) (0.285 versus 0.167) were also
observed between cohorts. Additionally, K2 and K(a) were found to have a
significant quadratic relationship (P = .031 and P = .005, respectively) with
v(e). CONCLUSIONS: Estimates of vascular permeability in brain tumors may be
simultaneously acquired from multiple-echo DSC-MR imaging via K(trans); however,
caution should be used in assuming a similar relationship for K2 and K(a).
PMID- 26427834
TI - Postoperative Imaging Findings following Sigmoid Sinus Wall Reconstruction for
Pulse Synchronous Tinnitus.
AB - BACKGROUND AND PURPOSE: Transmastoid sigmoid sinus wall reconstruction is a
surgical technique increasingly used for the treatment of pulsatile tinnitus
arising from sigmoid sinus wall anomalies. The imaging appearance of the temporal
bone following this procedure has not been well-characterized. The purpose of
this study was to evaluate the postoperative imaging appearance in a group of
patients who underwent this procedure. MATERIALS AND METHODS: The medical records
of 40 consecutive patients who underwent transmastoid sigmoid sinus wall
reconstruction were reviewed. Thirteen of 40 patients underwent postoperative
imaging. Nineteen CT and 7 MR imaging examinations were assessed for the
characteristics of the materials used for reconstruction, the impact of these on
the adjacent sigmoid sinus, and complications. RESULTS: Tinnitus resolved in 38
of 40 patients. Nine patients were imaged postoperatively for suspected
complications, including dural sinus thrombosis, facial swelling, and wound
drainage. Two patients underwent imaging for persistent tinnitus, and 2, for
development of tinnitus on the side contralateral to the side of surgery. The
materials used for reconstruction (NeuroAlloderm, HydroSet, bone pate)
demonstrated characteristic imaging appearances and could be consistently
identified. In 5 of 13 patients, there was extrinsic compression of the sigmoid
sinus by graft material. Dural sinus thrombosis occurred in 2 patients.
CONCLUSIONS: The imaging findings following sigmoid sinus wall repair are
characteristic. Graft materials may result in extrinsic compression of the
sigmoid sinus, and this finding may be confused with dural venous thrombosis.
Awareness of the imaging characteristics of the graft materials used enables this
differentiation.
PMID- 26427835
TI - Intensity of MRI Gadolinium Enhancement in Cerebral Adrenoleukodystrophy: A
Biomarker for Inflammation and Predictor of Outcome following Transplantation in
Higher Risk Patients.
AB - BACKGROUND AND PURPOSE: Outcomes following hematopoietic stem cell
transplantation for higher risk childhood-onset cerebral adrenoleukodystrophy are
variable. We explored whether a brain MR imaging gadolinium intensity scoring
system improves prediction of neurologic outcome. MATERIALS AND METHODS: We
developed a 4-point scale of gadolinium intensity relative to the choroid plexus:
0 = no enhancement; 1 = hypointense; 2 = isointense; 3 = hyperintense. The
interobserver concordance of the scale was assessed on 30 randomly chosen
studies. Scores were generated for 64 evaluable patients and compared with CSF
chitotriosidase levels, a known inflammatory marker correlating with outcomes
following transplantation. For 25 evaluable higher risk patients (Loes >=10), the
gadolinium intensity score was compared with longer term posttransplantation
clinical change. RESULTS: The gadolinium intensity scoring system showed good
interobserver reproducibility (kappa = 0.72). Of 64 evaluable boys, the score
positively correlated with average concomitant CSF chitotriosidase activity in
nanograms/milliliter/hour: 0: 2717, n = 5; 1: 3218, n = 13; 2: 6497, n = 23; and
3: 12,030, n = 23 (P < .01). For 25 evaluable higher risk patients, more intense
pretransplantation brain MR imaging gadolinium enhancement predicted greater
average loss on the adrenoleukodystrophy neurologic function scale following
transplantation: 0/1: adrenoleukodystrophy neurologic function scale score
difference = 4.3, n = 7; 2/3: adrenoleukodystrophy neurologic function scale
score difference = 10.4, n = 18 (P = .05). CONCLUSIONS: Gadolinium enhancement
intensity on brain MR imaging can be scored simply and reproducibly for cerebral
adrenoleukodystrophy. The enhancement score significantly correlates with
chitotriosidase. In boys with higher risk cerebral disease (Loes >=10), the
enhancement score itself predicts neurologic outcome following treatment. Such
data may help guide treatment decisions for clinicians and families.
PMID- 26427836
TI - Advanced Modeled Iterative Reconstruction in Low-Tube-Voltage Contrast-Enhanced
Neck CT: Evaluation of Objective and Subjective Image Quality.
AB - BACKGROUND AND PURPOSE: Dose-saving techniques in neck CT cause increased image
noise that can be counteracted by iterative reconstruction. Our aim was to
evaluate the image quality of advanced modeled iterative reconstruction (ADMIRE)
in contrast-enhanced low-tube-voltage neck CT. MATERIALS AND METHODS: Sixty-one
patients underwent 90-kV(peak) neck CT by using third-generation 192-section dual
source CT. Image series were reconstructed with standard filtered back-projection
and ADMIRE strength levels 1, 3, and 5. Attenuation and noise of the
sternocleidomastoid muscle, internal jugular vein, submandibular gland, tongue,
subscapularis muscle, and cervical fat were measured. Signal-to-noise and
contrast-to-noise ratios were calculated. Two radiologists assessed image noise,
image contrast, delineation of smaller structures, and overall diagnostic
acceptability. Interobserver agreement was calculated. RESULTS: Image noise was
significantly reduced by using ADMIRE compared with filtered back-projection with
the lowest noise observed in ADMIRE 5 (filtered back-projection, 9.4 +/- 2.4
Hounsfield units [HU]; ADMIRE 1, 8.3 +/- 2.8 HU; ADMIRE 3, 6.7 +/- 2.0 HU; ADMIRE
5, 5.4 +/- 1.7 HU; all, P < .001). Sternocleidomastoid SNR and internal jugular
vein-sternocleidomastoid contrast-to-noise ratios were significantly higher for
ADMIRE with the best results in ADMIRE 5 (all, P < .001). Subjective image
quality and image contrast of ADMIRE 3 and 5 were consistently rated better than
those for filtered back-projection and ADMIRE 1 (all, P < .001). Image noise was
rated highest for ADMIRE 5 (all, P < .005). Delineation of smaller structures was
voted higher in all ADMIRE strength levels compared with filtered back-projection
(P < .001). Global interobserver agreement was good (0.75). CONCLUSIONS: Contrast
enhanced 90-kVp neck CT is feasible, and ADMIRE 5 shows superior objective image
quality compared with filtered back-projection. ADMIRE 3 and 5 show the best
subjective image quality.
PMID- 26427837
TI - Spine Cryoablation: Pain Palliation and Local Tumor Control for Vertebral
Metastases.
AB - BACKGROUND AND PURPOSE: Percutaneous cryoablation has emerged as a minimally
invasive technique for the management of osseous metastases. The purpose of this
study was to assess the safety and effectiveness of percutaneous imaging-guided
spine cryoablation for pain palliation and local tumor control for vertebral
metastases. MATERIALS AND METHODS: Imaging-guided spine cryoablation was
performed in 14 patients (31 tumors) with vertebral metastases refractory to
conventional chemoradiation therapy or analgesics, to achieve pain palliation and
local tumor control in this retrospective study. Spinal nerve and soft-tissue
thermal protection techniques were implemented in all ablations. Patient response
was evaluated by a pain numeric rating scale administered before the procedure
and 1 week, 1 month, and 3 months after the procedure. Pre- and postprocedural
analgesic requirements (expressed as morphine-equivalent dosages) were also
analyzed at the same time points. Pre- and postprocedural cross-sectional imaging
was evaluated in all patients to assess local control (no radiographic evidence
of disease at the treated sites). Complications were monitored. Analysis of the
primary end points was undertaken via paired-comparison procedures by using the
Wilcoxon signed rank test. RESULTS: Thirty-one tumors were ablated in 14 patients
(9 women and 5 men; 20-73 years of age; mean age, 53 years). The most common
tumor location was in the lumbar spine (n = 14, 45%), followed by the thoracic
spine (n = 8, 26%), sacrum (n = 6, 19%), coccyx (n = 2, 6%), and cervical spine
(n = 1, 3%). There were statistically significant decreases in the median numeric
rating scale score and analgesic usage at 1-week, 1-month, and 3-month time
points (P < .001 for all). Local tumor control was achieved in 96.7% (30/31) of
tumors (median follow-up, 10 months). Two patients had transient postprocedural
unilateral lower extremity radiculopathy and weakness. CONCLUSIONS: Percutaneous
imaging-guided spine cryoablation is a safe and effective treatment for pain
palliation and local tumor control for vertebral metastases.
PMID- 26427838
TI - Proton Density MRI Increases Detection of Cervical Spinal Cord Multiple Sclerosis
Lesions Compared with T2-Weighted Fast Spin-Echo.
AB - BACKGROUND AND PURPOSE: There is a paucity of literature that supports the
Consortium of Multiple Sclerosis Centers guideline that proton density MR imaging
is a core spinal cord sequence. We hypothesized that proton density fast spin
echo imaging is superior to T2 fast spin-echo MR imaging for the detection of
cervical cord MS lesions. This study compared the detection rate and conspicuity
of cervical cord MS lesions on sagittal 1.5T proton density fast spin-echo and T2
fast spin-echo MR imaging. MATERIALS AND METHODS: One hundred consecutive
patients with MS imaged with 1.5T sagittal proton density fast spin-echo and T2
fast spin-echo cervical cord MR imaging between September 2012 and October 2013
were retrospectively included. The number of MS lesions detected on each sequence
was recorded; conspicuity was assessed quantitatively with the lesion-to-cord
contrast ratio and lesion-contrast-to-noise ratio. Statistical analysis was
performed by using the Wilcoxon signed rank test. RESULTS: Seventy-eight patients
had MS cord lesions detected. Proton density fast spin-echo imaging detected a
greater number of lesions (n = 181) compared with T2 fast spin-echo imaging (n =
137, P < .001). Fifteen patients (19%) with abnormal findings on proton density
fast spin-echo imaging had normal findings on T2 fast spin-echo imaging; no
patient with abnormal T2 fast spin-echo imaging findings had normal proton
density fast spin-echo imaging findings. Although proton density fast spin-echo
and T2 fast spin-echo imaging had similar lesion-to-cord contrast ratios (proton
density fast spin-echo, 0.32 +/- 0.01, versus T2 fast spin-echo, 0.33 +/- 0.01; P
= .43), proton density fast spin-echo had greater lesion-contrast-to-noise ratio
(proton density fast spin-echo, 82 +/- 3.0, versus T2 fast spin-echo, 64 +/- 2.6;
P < .001). CONCLUSIONS: Proton density fast spin-echo imaging is superior to T2
fast spin-echo MR imaging for the detection of cervical cord MS lesions. Proton
density fast spin-echo detects cord lesions in patients in whom T2 fast spin-echo
findings appear normal. This study forms the evidentiary base for the current
Consortium of Multiple Sclerosis Centers guideline that proton density imaging is
a core spinal cord sequence.
PMID- 26427839
TI - Dynamic Contrast-Enhanced MR Imaging in Head and Neck Cancer: Techniques and
Clinical Applications.
AB - In the past decade, dynamic contrast-enhanced MR imaging has had an increasing
role in assessing the microvascular characteristics of various tumors, including
head and neck cancer. Dynamic contrast-enhanced MR imaging allows noninvasive
assessment of permeability and blood flow, both important features of tumor
hypoxia, which is a marker for treatment resistance for head and neck cancer.
Dynamic contrast-enhanced MR imaging has the potential to identify early
locoregional recurrence, differentiate metastatic lymph nodes from normal nodes,
and predict tumor response to treatment and treatment monitoring in patients with
head and neck cancer. Quantitative analysis is in its early stage and
standardization and refinement of technique are essential. In this article, we
review the techniques of dynamic contrast-enhanced MR imaging data acquisition,
analytic methods, current limitations, and clinical applications in head and neck
cancer.
PMID- 26427840
TI - Proteomics discovery of radioresistant cancer biomarkers for radiotherapy.
AB - Radiotherapy (RT) is one of the most important strategies in cancer treatment.
Radioresistance is a major challenge to RT and results in locoregional recurrence
and metastasis. Thus, there is a great interest in investigating biomarkers to
distinguish radiosensitive from radioresistant (RR) cancer patients. The
development of proteomic techniques has sparked new searches for novel proteins
for cancer biomarker discovery. Modern proteomic techniques allow for a high
throughput analysis of samples with the visualization and quantification of
thousands of potential protein and peptide markers. The discovery of RR
biomarkers can provide a clue for predicting RT response and discover therapeutic
targets for developing personalised medicine of individual patients. In the past
decade, emerging advanced proteomic technologies have been performed to identify
radiation-related biomarkers in human cancers. This review discusses the mass
spectrometry (MS)-based proteomic techniques in RR cancer biomarker discovery,
summarises RR biomarkers identified in cancers from proteomics-based findings and
explores potential values of RR biomarkers for future clinical trials.
PMID- 26427841
TI - Identification of novel hereditary cancer genes by whole exome sequencing.
AB - Whole exome sequencing (WES) provides a powerful tool for medical genetic
research. Several dozens of WES studies involving patients with hereditary cancer
syndromes have already been reported. WES led to breakthrough in understanding of
the genetic basis of some exceptionally rare syndromes; for example,
identification of germ-line SMARCA4 mutations in patients with ovarian
hypercalcemic small cell carcinomas indeed explains a noticeable share of
familial aggregation of this disease. However, studies on common cancer types
turned out to be more difficult. In particular, there is almost a dozen of
reports describing WES analysis of breast cancer patients, but none of them yet
succeeded to reveal a gene responsible for the significant share of missing
heritability. Virtually all components of WES studies require substantial
improvement, e.g. technical performance of WES, interpretation of WES results,
mode of patient selection, etc. Most of contemporary investigations focus on
genes with autosomal dominant mechanism of inheritance; however, recessive and
oligogenic models of transmission of cancer susceptibility also need to be
considered. It is expected that the list of medically relevant tumor-predisposing
genes will be rapidly expanding in the next few years.
PMID- 26427842
TI - The effect of preoperative urinary tract infection on postoperative renal
function in prenatally diagnosed ureteropelvic junction obstruction: Indications
for the timing of pyeloplasty.
AB - PURPOSE: We reviewed renal function after pyeloplasty (PP) in cases of prenatally
diagnosed ureteropelvic junction obstruction (PDUPJO) to determine the impact of
preoperative urinary tract infection (UTI) on the timing of PP. METHODS: We
retrospectively reviewed 81 cases of PDUPJO diagnosed between 1998 and 2013.
Incidence of UTI was used to divide 37 kidneys requiring PP (3 bilateral) into U(
): UTI<=1; n=25, and U(+): UTI>=2; n=12 to compare age at PP, grade of
hydronephrosis (HN) on ultrasonography (US), glomerular filtration rate (GFR) on
diethylenetriaminepentacetic acid (DTPA) renography, and uptake on
dimercaptosuccinic acid (DMSA) scintigraphy pre/post PP. RESULTS: Age at first
UTI and age at PP were similar. HN improved significantly postPP in all cases.
Although DTPA and DMSA were similar prePP, improvement postPP was better in U(-)
than U(+), but only DMSA in U(-) was statistically significant (15.2%+/-4.0% vs.
20%+/-3.7%; p=0.049). There were no complications or UTI postPP. CONCLUSION: Two
or more UTIs would appear to be associated with postPP renal dysfunction in
PDUPJO. Thus, PP should be performed after the initial UTI but before the second
UTI.
PMID- 26427843
TI - Response to Letter to the Editor.
PMID- 26427844
TI - Triple-wavelength overlapping resonance Rayleigh scattering method for facile and
rapid assay of perfluorooctane sulfonate.
AB - In the present study, a novel triple-wavelength overlapping resonance Rayleigh
scattering (TWO-RRS) method had been well established to detect perfluorooctane
sulfonate (PFOS). We found that crystal violet (CV) could react with PFOS to form
1:1 ion-association complex by electrostatic attraction and hydrophobic effect
over a wide pH range (5.0~11.0) in less than 60 s. The complexes would further
self-aggregated into nanoparticles [CV-PFOS]n. Based on this phenomenon, not only
the absorption and Raman spectra were changed but also the resonance Rayleigh
scattering (RRS) intensities were significantly enhanced. And three new RRS peaks
located at 327, 492, and 654 nm were clearly observed, respectively. At the same
time, it was found that both the enhanced single-wavelength resonance Rayleigh
scattering (SW-RRS) and TWO-RRS intensities against the concentration of PFOS
showed an excellent correlation. The detection limits for the three single peaks
were 27.4 nmol L(-1) (13.7 MUg L(-1), 327 nm), 27.5 nmol L(-1) (13.8 MUg L(-1),
492 nm), and 31.4 nmol L(-1) (15.7 MUg L(-1), 654 nm), and for TWO-RRS method was
5.9 nmol L(-1) (3.0 MUg L(-1)). Moreover, it could be applied to determine PFOS
water samples successfully.
PMID- 26427845
TI - Assessment of typical natural processes and human activities' impact on the
quality of drinking water.
AB - This paper provides insight into the quality of groundwater used for public water
supply on the territory of Temerin municipality (Vojvodina, Serbia). The
following parameters were measured: color, turbidity, pH, KMnO4 consumption,
total dissolved solids (TDS), EC, NH4+, Cl-, NO2-, NO3-, Fe, Mn, As, Ca2+, Mg2+,
SO4(2-), HCO3-, K+, and Na+. The correlations and ratios among parameters that
define the chemical composition were determined aiming to identify main processes
that control the formation of the chemical composition of the analyzed waters.
Groundwater from three analyzed sources is Na-HCO3 type. Elevated organic matter
content, ammonium ion content, and arsene content are characteristic for these
waters. The importance of organic matter decay is assumed by positive correlation
between organic matter content and TDS, and HCO3- content. There is no evidence
that groundwater chemistry is determined by the depth of captured aquifer
interval. The main natural processes that control the chemistry of all analyzed
water are cation exchange and feldspar weathering. The dominant cause of As
concentration in groundwater is the use of mineral fertilizers and of KMnO4 in
urban area. The concentration of As and KMnO4 in the observed sources is
inversely proportional to the distance from agricultural land and urban area. 2D
model of distribution of As and KMnO4 is done, and it is applicable in detecting
sources of pollution. By using this model, we can quantify the impact of certain
pollutants on unfavorable content of some parameters in groundwater.
PMID- 26427846
TI - Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal
lobe epilepsy.
AB - Synaptic reorganization in the epileptic hippocampus involves altered excitatory
and inhibitory transmission besides the rearrangement of dendritic spines,
resulting in altered excitability, ion homeostasis, and cell swelling. The
potassium-chloride cotransporter-2 (KCC2) is the main chloride extruder in
neurons and hence will play a prominent role in determining the polarity of GABAA
receptor-mediated chloride currents. In addition, KCC2 also interacts with the
actin cytoskeleton which is critical for dendritic spine morphogenesis, and for
the maintenance of glutamatergic synapses and cell volume. Using
immunocytochemistry, we examined the cellular and subcellular levels of KCC2 in
surgically removed hippocampi of temporal lobe epilepsy (TLE) patients and
compared them to control human tissue. We also studied the distribution of KCC2
in a pilocarpine mouse model of epilepsy. An overall increase in KCC2-expression
was found in epilepsy and confirmed by Western blots. The cellular and
subcellular distributions in control mouse and human samples were largely
similar; moreover, changes affecting KCC2-expression were also alike in chronic
epileptic human and mouse hippocampi. At the subcellular level, we determined the
neuronal elements exhibiting enhanced KCC2 expression. In epileptic tissue,
staining became more intense in the immunopositive elements detected in control
tissue, and profiles with subthreshold expression of KCC2 in control samples
became labelled. Positive interneuron somata and dendrites were more numerous in
epileptic hippocampi, despite severe interneuron loss. Whether the elevation of
KCC2-expression is ultimately a pro- or anticonvulsive change, or both-behaving
differently during ictal and interictal states in a context-dependent manner
remains to be established.
PMID- 26427847
TI - Operative Results and Clinical Features of Chronic Stanford Type B Aortic
Dissection: Examination of 234 Patients Over 6 Years.
AB - OBJECTIVE/BACKGROUND: Recently, the indications for thoracic endovascular aortic
repair (TEVAR) have been expanding, and the applicability of TEVAR for acute type
B aortic dissection (TBAD) is proposed with regard to the high mortality of open
surgery for chronic TBAD. TEVAR in the acute phase may lead to remodeling of the
false lumen (FL), but it is controversial whether it completely resolves the
aortic expansion in the chronic phase. In this study, operative results and the
relationship between FL status and the time before surgical intervention were
retrospectively analyzed. METHODS: From January 2008 to September 2013, 234
patients underwent open surgery for chronic TBAD. Most patients were on left
heart bypass. By considering Japanese aortic disease treatment guidelines and the
smaller physique of Japanese patients, operative indications were aneurysm >50 mm
in diameter or rapid aneurysm enlargement of >5 mm in a 6 month period. RESULTS:
In 180 cases, the FL was patent. The mean interval between onset of TBAD and
operation was 61 +/- 54 months. There was no significant difference between
patients in the patent FL group and those in the thrombosed FL group (p = .44).
Mean ratio of FL diameter to maximum aortic diameter (FL/AD) was 0.64 +/- 0.21.
There was no correlation between FL and AD before the operation (r = .12).
Descending thoracic aortic replacement (DTAR) was performed in 127 cases and
thoracic ascending aortic replacement (TAAR) in 107 cases (Crawford type I, n =
9; Crawford type II, n = 65; Crawford type III and IV, n = 22, respectively; Safi
type V, n = 11). The overall operative mortality was 6.8%: 3.9% (5/127) for DTAR
and 10.3% (11/107) for TAAR. The three year survival was 86.7, and the freedom
from re-intervention rate was 97.0%. CONCLUSION: Enlargement of uncomplicated
TBAD in the chronic phase was poorly related to FL status and the results of open
repair have improved. However, further prospective study is necessary.
PMID- 26427848
TI - Linking landscape development intensity within watersheds to methyl-mercury
accumulation in river sediments.
AB - An indicator of the disturbance of natural systems, the landscape development
intensity (LDI) index, was used to assess the potential for land-use within
watersheds to influence the production/accumulation of methyl-mercury (MeHg) in
river sediments. Sediment samples were collected from locations impacted by well
identified land-use types within the Mobile-Alabama River Basin in Southeastern
USA. The samples were analyzed for total-Hg (THg) and MeHg concentrations and the
obtained values correlated to the calculated LDI indexes of the sampled
watersheds to assess the impact of prevalent land use/land cover on MeHg
accumulation in sediments. The results show that unlike THg, levels of MeHg found
in sediments are impacted by the LDI indexes. Overall, certain combinations of
land-use types within a given watershed appear to be more conducive to MeHg
accumulation than others, therefore, pointing to the possibility of targeting
land-use practices as potential means for reducing MeHg accumulation in
sediments, and ultimately, fish contamination.
PMID- 26427849
TI - Traumatic Experience and Somatoform Dissociation Among Spirit Possession
Practitioners in the Dominican Republic.
AB - Recent studies in African contexts have revealed a strong association between
spirit possession and severe trauma, with inclusion into a possession cult
serving at times a therapeutic function. Research on spirit possession in the
Dominican Republic has so far not included quantitative studies of trauma and
dissociation. This study evaluated demographic variables, somatoform dissociative
symptoms, and potentially traumatizing events in the Dominican Republic with a
group of Vodou practitioners that either do or do not experience spirit
possession. Inter-group comparisons revealed that in contrast to non-possessed
participants (n = 38), those experiencing spirit possession (n = 47) reported
greater somatoform dissociation, more problems with sleep, and previous exposure
to mortal danger such as assaults, accidents, or diseases. The two groups did not
differ significantly in other types of trauma. The best predictor variable for
group classification was somatoform dissociation, although those items could also
reflect the experience of followers during a possession episode. A factor
analysis across variables resulted in three factors: having to take
responsibility early on in life and taking on a professional spiritual role;
traumatic events and pain; and distress/dissociation. In comparison with the non
possessed individuals, the possessed ones did not seem to overall have a
remarkably more severe story of trauma and seemed to derive economic gains from
possession practice.
PMID- 26427850
TI - Phylogenetic analysis of Indian rabies virus isolates targeting the complete
glycoprotein gene.
AB - Rabies a fatal viral zoonosis is endemic in India. There is no report on
phylogenetic study of Indian rabies virus isolates based on the complete G gene.
In the present study, a total of 25 rabies positive brain samples collected
during 2001-2014 from North India (UP, MP, Delhi, Rajasthan), South India (Kerala
and Karnataka) and Gujarat states belonging to six different host species were
subjected to G gene amplification by RT-PCR as three overlapping fragments of 881
bp, 991 bp and 618 bp. Phylogenetic analysis revealed that all Indian rabies
virus isolates are genetically closely related with Arctic-like 1a lineage
viruses. However, two distinct clusters were identified namely, India South and
India North. All the Indian rabies isolates had 95.5-100% homology related to
geography, but not to host species. Deduced amino acids on comparison revealed
two amino acid changes, aa 356 in ECTO; N->K and aa 458; M->I, which were found
to distinguish between the India South and India North isolates.
PMID- 26427851
TI - Selective Lifelong Destruction of Brain Monoaminergic Nerves Through Perinatal
DSP-4 Treatment.
AB - N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a highly selective
neurotoxin for noradrenergic projections originating from the locus coeruleus
(LC). The outcome of the systemic DSP-4 treatment of newborn rats is an
alteration in postnatal development of the noradrenergic system, involving the
permanent denervation of distal noradrenergic projection areas (neocortex,
hippocampus, spinal cord), accompanied by noradrenergic hyperinnervation in
regions proximal to the LC cell bodies (cerebellum, pons-medulla). DSP-4 is well
tolerated by developing rats and does not increase the mortality rate. Permanent
noradrenergic denervation in the cerebral cortex and spinal cord is present at
all developmental stages, although this effect is more pronounced in rats treated
with DSP-4 at an early age, i.e., up to postnatal day 5 (PND 5). Notably,
regional hyperinnervation is a hallmark of neonatal DSP-4 treatment, which is not
observed after either prenatal or adult DSP-4 application. In contrast to robust
biochemical changes in the brain, DSP-4 treatment of newborn rats has a marginal
effect on arousal and cognition functions assessed in adulthood, and these
processes are critically influenced by the action of the noradrenergic
neurotransmitter, norepinephrine (NE). Conversely, neonatal DSP-4 does not
significantly affect 5-hydroxytryptamine (serotonin; 5-HT), dopamine (DA), gamma
aminobutyric acid (GABA), and histamine levels in brain. However, as a
consequence of altering the functional efficacy of 5-HT1A, 5-HT1B, DA, and GABA
receptors, these neurotransmitter systems are profoundly affected in adulthood.
Thus, the noradrenergic lesion obtained with neonatal DSP-4 treatment represents
a unique neurobiological technique for exploring the interplay between various
neuronal phenotypes and examining the pathomechanism of neurodevelopmental
disorders.
PMID- 26427853
TI - Loss of glucocerebrosidase 1 activity causes lysosomal dysfunction and alpha
synuclein aggregation.
PMID- 26427852
TI - Murine Sca1(+)Lin(-) bone marrow contains an endodermal precursor population that
differentiates into hepatocytes.
AB - The direct differentiation of hepatocytes from bone marrow cells remains
controversial. Several mechanisms, including transdifferentiation and cell
fusion, have been proposed for this phenomenon, although direct visualization of
the process and the underlying mechanisms have not been reported. In this study,
we established an efficient in vitro culture method for differentiation of
functioning hepatocytes from murine lineage-negative bone marrow cells. These
cells reduced liver damage and incorporated into hepatic parenchyma in two
independent hepatic injury models. Our simple and efficient in vitro protocol for
endodermal precursor cell survival and expansion enabled us to identify these
cells as existing in Sca1(+) subpopulations of lineage-negative bone marrow
cells. The endodermal precursor cells followed a sequential developmental pathway
that included endodermal cells and hepatocyte precursor cells, which indicates
that lineage-negative bone marrow cells contain more diverse multipotent stem
cells than considered previously. The presence of equivalent endodermal precursor
populations in human bone marrow would facilitate the development of these cells
into an effective treatment modality for chronic liver diseases.
PMID- 26427855
TI - Erratum to: Streptomyces mangrovi sp. nov., isolated from mangrove forest
sediment.
PMID- 26427856
TI - Phytomonospora cypria sp. nov., isolated from soil.
AB - A Gram-stain positive actinobacterial strain, designated KT1403(T), was isolated
from a soil sample, collected from Karpaz, Magusa, Northern Cyprus, and
characterised using a polyphasic approach. Morphological characteristics and
chemotaxonomic data indicated that the strain belongs to the genus
Phytomonospora. The cell wall of the novel strain contained meso-diaminopimelic
acid and galactose, glucose and mannose as the major sugars in whole cell
hydrolysates. The polar lipids in the cell membrane were identified as
diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine,
phosphatidylinositol, an unidentified aminophospholipid and three unidentified
glycolipids. The predominant menaquinones were MK-10(H6) and MK-10(H4). The major
fatty acids were found to be iso C15:0 , anteiso C15:0 and anteiso C17:0.
Phylogenetic analysis based on 16S rRNA gene sequences showed that strain
KT1403(T) belongs to the genus Phytomonospora with a sequence similarity of 99.73
% with Phytomonospora endophytica, the type species of the genus. DNA-DNA
hybridization further differentiated strain KT1403(T) from its near phylogenetic
neighbour, P. endophytica DSM 45386(T) (29.0 +/- 2.2 % DNA relatedness).
Therefore, it is proposed that strain KT1403(T) represents a novel species of the
genus Phytomonospora, for which the name Phytomonospora cypria sp. nov. is
proposed. The type strain is KT1403(T) (=KCTC 29479(T) = DSM 46767(T)).
PMID- 26427854
TI - Self-Assembling Peptide Nanofiber Containing Long Motif of Laminin Induces Neural
Differentiation, Tubulin Polymerization, and Neurogenesis: In Vitro, Ex Vivo, and
In Vivo Studies.
AB - Spinal cord injury (SCI) in humans stayed a ruining and healless disorder. Since
longer laminin motif (CQAASIKVAV (CQIK)) better mimics conformation of native
region in active site than isoleucine-lysine-valine-alanine-valine (IKVAV) and
resulted in improved cellular response so, for the first time in this study, CQIK
bounded with two glycines spacer and (RADA)4 as a self-assembling peptide
nanofiber backbone (-CQIK) was used. The purpose of this study was to investigate
the role of -CQIK in neural differentiation of human endometrial-derived stromal
cells (hEnSCs) in vitro, tubulin polymerization ex vivo, and assess the
supportive effect of this hydrogel in an animal model of chronic SCI. Results
disclosed that proton concentration has direct effect on hEnSCs membrane damage
but not on neuroblastoma cells. However, cell viability of neuroblastoma
encapsulated into -CQIK was higher than hEnSCs at the concentration of 0.125 %
v/w. Gene expression data confirmed neurogenesis, TH over-expression, and glial
fibrillary acidic protein (GFAP) suppression eventually through alpha6 and beta1
integrin site. However, it revealed higher neurogenesis as compared to bone
morrow homing peptides (BMHP). Although, Basso, Beattie, Bresnahan (BBB) score of
chronic model of SCI in rat was higher than control and phosphate-buffered saline
(PBS) group but significantly was less than BMHP group. However, -CQIK had
induced neurite outgrowth and myelination and inhibited astrogliosis. Tubulin
polymerization data using UV spectroscopy showed higher degree of polymerization.
However, tubulin polymerization was dependent on nanofiber concentration. Based
on our results, it might be concluded that peptidic nanofiber containing long
motif of laminin holds great promise for spinal cord injury recovery with
increment of neurogenesis and astrogliosis decrement.
PMID- 26427857
TI - Nocardia arizonensis sp. nov., obtained from human respiratory specimens.
AB - In 2008, three clinical isolates (W9405(T), W9409 and W9575) were obtained from
bronchial wash or sputum specimens from patients from the state of Arizona and
characterised by polyphasic analysis. All three clinical isolates 16S rRNA gene
sequences were found to be 100% identical to each other and showed the strains
belong in the genus Nocardia. BLASTn searches in the GenBank database of near
full-length 16S rRNA gene sequences showed the highest sequence similarities to
the type strains of Nocardia takedensis (98.3%, sequence similarity), Nocardia
lijiangensis (97.4%), Nocardia harenae (97.4%), and Nocardia xishanensis (97.1%).
The DNA-DNA relatedness between isolate W9405(T) and the type strain of N.
takedensis is 26.0 +/- 2.4% when measured in silico using genomic DNA sequences.
The G+C content of isolate W9405(T) is 68.6 mol%. Chemotaxonomic analyses of the
clinical isolates were consistent with their assignment to the genus Nocardia:
whole cell hydrolysates contain meso-diaminopimelic acid as the diagnostic
diamino acid of peptidoglycan; the whole-cell sugars are arabinose and galactose;
the predominant phospholipids include diphosphatidylglycerol,
phosphatidylethanolamine and phosphatidylinositol; MK-8-(H4)(omega-cyc) as the
major menaquinone; mycolic acids ranging from 38 to 62 carbon atoms; and palmitic
acid, tuberculostearic acid, palmitelaidic acid and oleic acid are the major
fatty acids. Genus and species specific profiles were obtained following analysis
by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass
spectra of the clinical isolates. All isolates were found to be intermediately
resistant or resistant to minocycline and resistant to ciprofloxacin but were
susceptible to amikacin, imipenem and linezolid. Our polyphasic analysis suggest
the three clinical isolates obtained from patients in Arizona represent a novel
species of Nocardia for which we propose the name Nocardia arizonensis, with
strain W9405(T) (=DSM 45748(T) = CCUG 62754(T) = NBRC 108935(T)) as the type
strain.
PMID- 26427858
TI - Sphingobium soli sp. nov. isolated from rhizosphere soil of a rose.
AB - Strain THG-SQA7(T), a Gram-negative, strictly aerobic, non-motile, rod-shaped
bacterium was isolated from rhizosphere soil of a rose in PR China. Strain THG
SQA7(T) is closely related to the members of the genus Sphingobium, showing the
highest 16S rRNA gene sequence similarities with Sphingobium lactosutens KACC
18100(T) (98.2%) and Sphingobium abikonense KCTC 2864(T) (98.1%). The DNA-DNA
relatedness between strain THG-SQA7(T) and S. lactosutens KACC 18100(T) and S.
abikonense KCTC 2864(T) was 26.2 +/- 0.9 and 28.3 +/- 1.2%, respectively.
Chemotaxonomic data showed that strain THG-SQA7(T) possesses ubiquinone Q-10 as
the predominant respiratory quinone, and C(18:1)omega7c, C(16:0), summed feature
3 (C(16:1)omega7c and/or C(16:1)omega6c) and C(14:0) 2OH as the major fatty
acids. The major polar lipids were found to be phosphatidylethanolamine,
phosphatidylmonomethylethanolamine, phosphatidylglycerol, sphingoglycolipid,
diphosphatidylglycerol and phosphatidyldimethylethanolamine. Based on these
results, together with phenotypic characterization, a novel species, Sphingobium
soli sp. nov. is proposed.with the type strain is THG-SQA7(T) (=CCTCC AB
2015125(T) = KCTC 42607(T)).
PMID- 26427859
TI - Breast cancer diagnosis, patterns of care and burden of disease in Queensland,
Australia (1998-2004): does being Indigenous make a difference?
AB - OBJECTIVES: We compared patterns of care, comorbidity, disability-adjusted life
years (DALYs) and survival in Indigenous and non-Indigenous women with breast
cancer in Queensland, Australia (1998-2004). METHODS: A cohort study of
Indigenous (n = 110) and non-Indigenous women (n = 105), frequency matched on age
and remoteness. We used Pearson's Chi-squared analysis to compare proportions,
hazard models to assess survival differences and calculated disability-adjusted
life years (DALYs). RESULTS: Indigenous women were more likely to be socially
disadvantaged (43 vs. 20 %, p < 0.01) have comorbidity (42 vs. 18 % p < 0.01),
and have regional spread or distant metastasis (metastasis, 51 vs. 36 %, p =
0.02) than non-Indigenous women; there was no difference in treatment patterns.
More Indigenous women died in the follow-up period (p = 0.01). DALY's were 469
and 665 per 100,000 for Indigenous and non-Indigenous women, respectively, with a
larger proportion of the burden attributed to premature death among the former
(63 vs. 59 %). CONCLUSIONS: Indigenous women with breast cancer received
comparable treatment to their non-Indigenous counterparts. The higher proportion
of DALYs related to early death in Indigenous women suggests higher fatality with
breast cancer in this group. Later stage at diagnosis and higher comorbidity
presence among Indigenous women reinforce the need for early detection and
improved management of co-existing disease.
PMID- 26427860
TI - Educational differentials in cancer mortality and avoidable deaths in Lithuania,
2001-2009: a census-linked study.
AB - OBJECTIVES: We investigate relative mortality inequalities by education for
detailed cancer sites and provide estimates of deaths which could have been
avoided through the elimination of these inequalities. METHODS: A census-linked
dataset based on a follow-up of all residents registered in the 2001 census was
used for the analysis. Mortality rate ratios were estimated by employing
multivariate Poisson regression models for count data. RESULTS: An inverse
educational gradient was observed for 11 cancer sites among men and for three
cancer sites among women. Substantial shares of these cancer deaths would have
been avoided if mortality among less educated groups had been the same as
mortality among highly educated groups. CONCLUSIONS: Cancer control plans must
consider socioeconomic inequalities and propose ways to improve prevention
measures aimed at disadvantaged groups.
PMID- 26427861
TI - Support for smoke-free policies in the Cyprus hospitality industry.
AB - OBJECTIVES: The present study used attitudinal and behavioural indicators to
measure support for smoke-free policies among employers and employees in the
hospitality industry in Cyprus. METHODS: A representative sample of 600
participants (95 % response rate) completed anonymous structured questionnaires
on demographic variables, smoking status, exposure to second-hand smoke at work
and related health beliefs, social norms, and smoke-free policy support. RESULTS:
Participants were predominantly males (68.3 %), with a mean age of 40 years (SD =
12.69), and 39.7 % were employers/owners of the hospitality venue. Analysis of
variance showed that employers and smokers were less supportive of smoke-free
policies, as compared to employees and non-smokers. Linear regression models
showed that attitudes towards smoke-free policy were predicted by smoking status,
SHS exposure and related health beliefs, and social norm variables. Logistic
regression analysis showed that willingness to confront a policy violator was
predicted by SHS exposure, perceived prevalence of smoker clients, and smoke-free
policy attitudes. CONCLUSIONS: SHS exposure and related health beliefs, and
normative factors should be targeted by interventions aiming to promote policy
support in the hospitality industry in Cyprus.
PMID- 26427863
TI - Charge-Transfer Emission in Organoboron-Based Biphenyls: Effect of Substitution
Position and Conformation.
AB - A series of organoboron-based biphenyls o,o'-NMe2, o,p'-NMe2, p,p'-NMe2, which
contain an electron-donating NMe2 and an electron-accepting BMes2 groups at o,o'
, o,p'-, p,p'-positions of biphenyl skeleton, respectively, as well as o,o'-NBn2,
which contains more bulky NBn2 rather than NMe2, were fully characterized to
explore the effect of structural modification on the intramolecular charge
transfer emissions. In addition to significant effect of substitution position on
photophysical properties, remarkable influence of conformation was also observed
for o,o'-substituted compounds. The emission is substantially blue-shifted as
conformation changes from the location of NMe2 and BMes2 at same side of biphenyl
axis with a close B...N distance, and thus direct B...N electronic interaction in
o,o'-NMe2, to the location of NBn2 and BMes2 on two opposite sides in o,o'-NBn2.
And o,o'-NMe2 exhibits the longest emission wavelength, but the shortest
absorption wavelength, and thus largest Stokes shift among these four organoboron
based biphenyls in both solution and solid state. The theoretical calculations
demonstrated that the unique structure of o,o'-NMe2, in which boryl and amino
located at the same side of biphenyl axis with close B...N distance and direct
B...N electronic interaction, is helpful to stabilize the lowest singly occupied
orbital in the exited state.
PMID- 26427862
TI - Unemployment, health, and education of HIV-infected males in Germany.
AB - OBJECTIVES: The present study on people living with HIV/AIDS (PLWHA) identifies
socio-demographic and health-related factors corresponding with their labour
market participation. METHODS: The study sample bases on a German observational
sub-study of 527 male PLWHA. The present analysis is restricted to male PLWHA in
working age. By means of a multivariate regression, we identify factors that
contribute to unemployment and job loss. RESULTS: The probability to be
unemployed is significantly negatively correlated with age above 40 years and
graduation from university and positively correlated with problems with daily
activities (frailty) and disease severity (CDC stage C). The probability of
employment loss during the 2-year observation period is significantly negatively
correlated with the educational level, whereas frailty and hepatitis C (HCV) co
infection increase the odds of employment loss. CONCLUSIONS: As problems to
manage daily activities and disease progression are associated with unemployment,
an effective HIV treatment is an important cornerstone for employment. This is
also true for the management of comorbidities, such as HCV co-infection, which
also negatively affects employment status in our study.
PMID- 26427864
TI - Predicting the mineral composition of ureteral stone using non-contrast computed
tomography.
AB - We investigated the correlation between computed tomography (CT) density of
ureteral stones and their mineral composition. A total of 346 patients who
underwent ureteroscopic lithotripsy for calculi all fragments of which were
acquired at a single institution from 2009 to 2011 were analyzed. The maximum and
mean CT densities were measured preoperatively. A mineral analysis revealed
calcium oxalate in 203 (58.7 %), mixed calcium oxalate and calcium phosphate in
78 (23.0 %), calcium phosphate in 18 (5.2 %), uric acid in 8 (2.3 %), struvite in
3 (0.9 %), and cysteine in 5 (1.4 %). The mean Hounsfield units (HUs) of the CT
density were 1046 HUs in calcium oxalate, 1101 HUs in mixed calcium oxalate and
calcium phosphate, 835 HUs in calcium phosphate, 549 HUs in uric acid, 729 HUs in
struvite, and 698 HUs in cystine. The HUs in calcium oxalate were significantly
higher than those in uric acid (p < 0.01) and struvite (p < 0.01). Those in
monohydrate stones were significantly higher, compared with dehydrate stones (p <
0.05). We analyzed the largest number of stones than each published study to
correlate their mineral composition and CT density. Calcium component stones
showed significantly higher CT densities than other types.
PMID- 26427865
TI - Conditional survival for pediatric and adolescent patients with cancer:
Implications for survivorship care.
AB - PURPOSE: Few studies have evaluated conditional survival (probability of
surviving y years given patients have already survived x years) for
pediatric/adolescent patients diagnosed with cancer. To provide more accurate
information on ongoing survival, we evaluate conditional survival for pediatric
and adolescent patients with cancer. METHODS: The statewide Utah Cancer Registry
identified 3344 patients born in Utah diagnosed with cancer at ages 0-21 years,
from 1973 to 2009. The Utah Population Database provided demographic information.
We estimated five-year conditional survival at diagnosis, and one and three years
after diagnosis, by risk factors such as cancer type, sex, diagnosis age and
treatment era (1973-1994 vs. 1995-2009). RESULTS: Conditional survival estimates
at one (85.1%, 95% CI: 83.7-86.5) and three years (92.9%, 95% CI: 91.8-93.9)
after diagnosis were significantly higher than survival at diagnosis (77.2%, 95%
CI: 75.6-78.9), although results varied by cancer type and initial prognosis.
Diagnosis age affected survival for cancers where age is a risk factor. For
example, five-year survival at one year after diagnosis was higher for younger
(<= 18 months of age) patients compared to older (>18 months) patients with
neuroblastoma (95.4%, 95% CI: 90.9-99.9 vs. 56.8%, 95% CI: 41.8-71.7, p<0.001).
Conditional survival improved over time for many cancers. Minimal differences
were observed by sex. CONCLUSION: Substantial improvements were observed in
conditional survival at one and three years after diagnosis compared with
survival at diagnosis. Several risk factors affected these outcomes. Clearer
understandings of survival will help in administering effective survivorship care
and decreasing prognosis-related anxiety/stress for patients and families.
PMID- 26427866
TI - Comparison of pulpal anesthesia and cardiovascular parameters with lidocaine with
epinephrine and lidocaine with clonidine after maxillary infiltration in type 2
diabetic volunteers.
AB - OBJECTIVES: The pulpal anesthetic and cardiovascular parameters obtained by 2 %
lidocaine with epinephrine (LE; 1:80,000) or clonidine (LC; 15 mcg/ml) were
studied in diabetes mellitus (DM) type 2 and healthy volunteers (72), after
maxillary infiltration anesthesia. MATERIALS AND METHODS: Onset and duration of
pulpal anesthesia were measured by electric pulp tester; vasoconstrictive effect
of used local anesthetic mixtures by laser Doppler flowmetry (LDF) through pulpal
blood flow (PBF); systolic blood pressure (SBP), diastolic blood pressure (DBP),
and heart rate (HR) were registered by electrocardiogram monitoring. RESULTS:
Onset of pulpal anesthesia was shorter for LC than for LE in healthy, while it
was not different in diabetic participants; duration of pulpal anesthesia was
significantly longer in type 2 diabetic participants, regardless of used
anesthetic mixture. Significant reduction of PBF with LE was observed during 45
min in healthy and 60 min in diabetic participants, while with LC such reduction
was observed during 45 min in both groups. LE caused a significant increase of
SBP in the 5th and 15th minutes in diabetic versus healthy participants, while LC
decreased SBP from the 10th to 60th minutes in healthy versus diabetic
participants. CONCLUSIONS: DM type 2 influences duration of maxillary
infiltration anesthesia obtained with LE and LC, and systolic blood pressure
during LE anesthesia. CLINICAL RELEVANCE: The obtained results provide elements
for future protocols concerning intraoral local anesthesia in DM type 2 patients.
PMID- 26427867
TI - Compliance and persistence with treatment with parathyroid hormone for
osteoporosis. A Danish national register-based cohort study.
AB - Medical intervention is important in the treatment of osteoporosis, and
compliance with medical treatment is essential for an optimal outcome. Based on
Danish national registers, we found that compliance with parathyroid hormone
(PTH) treatment is high and associated with marital status, working status, and
type of PTH treatment. PURPOSE: Compliance and persistence are essential for an
optimal outcome during medical treatment of osteoporosis. We aimed to evaluate
compliance and persistence with treatment with PTH in daily clinical practice in
Danish patients and to describe factors affecting compliance. METHODS: Register
based nationwide cohort study on all patients in Denmark initiates PTH or
analogue treatment for osteoporosis in 2003-2010 (n = 4281). PTH drugs included
were the PTH analogue teriparatide(1-34) and recombinant human PTH (rhPTH(1-84)).
Compliance with treatment was calculated by using medication possession ratio
(MPR). RESULTS: In the study period, 3702 patients were exclusively treated with
teriparatide and 579 were exclusively treated with rhPTH(1-84). We found that for
patients persistent with therapy for at least 18 months and with MPR >0.8, 83 %
of the patients in the teriparatide group were compliant versus 72 % in the
recombinant PTH group (p < 0.01). Being married/cohabiting, still in the labor
market, and taking teriparatide were significantly associated with higher
compliance, whereas age, gender, level of education, income, alcoholism, and
Charlson comorbidity index were not associated with compliance. CONCLUSION:
Compliance with PTH treatment overall is high, with teriparatide compliance
higher than rhPTH(1-84), in patients persistent to therapy for 18 months.
Compliance is associated with marital status, working status, and type of PTH
treatment.
PMID- 26427868
TI - Down-regulation of uterine LIF expression induced by the hormonal level disorder
causes embryo implantation loss after mice exposed to carbon disulfide at peri
implantation.
AB - Carbon disulfide (CS2) exposure can cause embryo implantation loss but the
mechanism remains unclear. Earlier study revealed that the 4th day of gestation
(GD4) and GD5 were the most sensitive exposure time on which the number of
implanted embryos decreased obviously in mice. Leukemia inhibitory factor (LIF)
in maternal uterine tissue is involved in embryo implantation, which is produced
by endometrium and Th2 cells that participate in cellular adhesion of maternal
fetal interface. We herein investigated the effect of CS2 on the expression of
LIF in uterine tissue and its regulatory mechanism in Kunming mice. Exposure was
on GD3, GD4, GD5 and GD6, respectively, single administration (631.4 mg/kg), and
the indexes were arranged in time series after exposure. The results showed that
LIF gene breakage was captured at the 18th hour after exposure by Comet-FISH and
the protein and mRNA of LIF in uterine tissue were down-regulated after exposure
through the peri-implantation period. In addition, sex steroid hormones,
progesterone (P4) and oestrogen (E2) were detected since they can stimulate
synthesis of LIF from endometrial cells. Results showed that P4 and E2 in serum
were down-regulated at all the endpoints of CS2 exposure groups. These findings
suggested that the down-regulated LIF induced by the decreased P4 and E2 after
mice exposure to CS2 might be important reasons for implantation disorders.
PMID- 26427869
TI - The effect of rat bone marrow derived mesenchymal stem cells transplantation for
restoration of olfactory disorder.
AB - The purpose of the study was to investigate the effect of bone marrow-derived
mesenchymal stem cells (BMSCs) transplantation on olfactory epithelium (OE) of
morphologic and functional restoration following neural Sensorineural Disorder in
rats. Except the Normal group, twenty-one rats underwent Triton X-100 (TX-100)
irrigation to induce degeneration of OE, and then BMSCs and PBS were treated from
the both medial canthus to the rear part of the both nasal cavity into the
experimental group and then were observed for restoration according to time
point. At two and four weeks after transplantation with BMSCs, restoration of OE
was observed with olfactory marker protein (OMP) and behavioral test. And we
observed the expression of OMP, nerve growth factor (NGF) and brain-derived
neurotrophic factor (BDNF). After TX-100 irrigation, the OE almost disappeared in
3 days. At four weeks after transplantation with BMSCs, the thickness and
cellular composition of OE was considerably restored to normal group and
expression of OMP was markedly increased when compared with PBS group and reduced
the searching time in the behavioral test. Furthermore at two weeks after
treatment with BMSCs, expression of NGF and BDNF was greatly increased when
compared with PBS group. However at four weeks after treatment with BMSCs,
expression of NGF and BDNF was slightly decreased. Our results suggest the BMSCs
transplantation affect restoration of OE and olfaction, most likely via
regulation of the neurotrophic factor expression, especially the expression of
NGF and BDNF and has a possibility of a new therapeutic strategy for the
treatment of olfactory disorder caused by the degeneration of OE.
PMID- 26427870
TI - Therapeutic effects of antibiotic drug tigecycline against cervical squamous cell
carcinoma by inhibiting Wnt/beta-catenin signaling.
AB - Aberrant activation of the Wnt/beta-catenin signaling pathway is common in human
cervical cancers and has great potential therapeutic value. We show that
tigecycline, a FDA-approved antibiotic drug, targets cervical squamous cell
carcinoma through inhibiting Wnt/beta-catenin signaling pathway. Tigecycline is
effective in inducing apoptosis, inhibiting proliferation and anchorage
independent colony formation of Hela cells. The inhibitory effects of tigecycline
are further enhanced upon combination with paclitaxel, a most commonly used
chemotherapeutic drug for cervical cancer. In a cervical xenograft model,
tigecycline inhibits tumor growth as a single agent and its combination with
paclitaxel significantly inhibits more tumor growth throughout the duration of
treatment. We further show that tigecycline decreases level of both cytoplasmic
and nuclear beta-catenin and suppressed Wnt/beta-catenin-mediated transcription
through increasing levels of Axin 1 in Hela cells. In addition, stabilization or
overexpression of beta-catenin using pharmacological and genetic approaches
abolished the effects of tigecycline in inhibiting proliferation and inducing
apoptosis of Hela cells. Our study suggests that tigecycline is a useful addition
to the treatment armamentarium for cervical cancer and targeting Wnt/beta-catenin
represents a potential therapeutic strategy in cervical cancer.
PMID- 26427873
TI - The N-terminal domains determine cellular localization and functions of the Doa4
and Ubp5 deubiquitinating enzymes.
AB - Ubiquitination is involved in numerous cellular regulatory mechanisms including
the cell cycle, signal transduction and quality control. Ubiquitin modifies
proteins by consecutive actions of ubiquitin-activating/conjugating enzymes.
Attachment of ubiquitin is reversible. Deubiquitinating enzymes are responsible
for removal of ubiquitin from ubiquitin-protein conjugates. Genome of the yeast
Saccharomyces cerevisiae encodes structurally related but functionally distinct
enzymes - Doa4 and Ubp5. Doa4 is involved in general ubiquitin-dependent
proteolysis and is responsible for deubiquitination of ubiquitin-protein
conjugates at the cytoplasmic face of the late endosome. The N-terminal domain
targets the enzyme to the endosome membrane after ESCRT-III complex has formed
there. By contrast, corresponding region of homologous Ubp5 is critical for its
bud neck localization in dividing cells. Conceivably, Ubp5 plays an essential
role in cytokinesis. Here we show that Doa4 physically interacts with the ESCRT
III component Snf7 and preferentially cleaves Lys63-linked ubiquitin oligomers
involved in membrane protein trafficking. We also demonstrate that the unstable
regulator of cytokinesis Hof1 accumulates in proteasomal mutants and is required
for cellular localization of Ubp5.
PMID- 26427872
TI - Maternal diabetes triggers DNA damage and DNA damage response in neurulation
stage embryos through oxidative stress.
AB - DNA damage and DNA damage response (DDR) in neurulation stage embryos under
maternal diabetes conditions are not well understood. The purpose of this study
was to investigate whether maternal diabetes and high glucose in vitro induce DNA
damage and DDR in the developing embryo through oxidative stress. In vivo
experiments were conducted by mating superoxide dismutase 1 (SOD1) transgenic
male mice with wild-type (WT) female mice with or without diabetes. Embryonic day
8.75 (E8.75) embryos were tested for the DNA damage markers, phosphorylated
histone H2A.X (p-H2A.X) and DDR signaling intermediates, including phosphorylated
checkpoint 1 (p-Chk1), phosphorylated checkpoint 2 (p-Chk2), and p53. Levels of
the same DNA damage markers and DDR signaling intermediates were also determined
in the mouse C17.2 neural stem cell line. Maternal diabetes and high glucose in
vitro significantly increased the levels of p-H2A.X. Levels of p-Chk1, p-Chk2,
and p53, were elevated under both maternal diabetic and high glucose conditions.
SOD1 overexpression blocked maternal diabetes-induced DNA damage and DDR in vivo.
Tempol, a SOD1 mimetic, diminished high glucose-induced DNA damage and DDR in
vitro. In conclusion, maternal diabetes and high glucose in vitro induce DNA
damage and activates DDR through oxidative stress, which may contribute to the
pathogenesis of diabetes-associated embryopathy.
PMID- 26427871
TI - Stem cell-derived vasculature: A potent and multidimensional technology for basic
research, disease modeling, and tissue engineering.
AB - Proper blood vessel networks are necessary for constructing and re-constructing
tissues, promoting wound healing, and delivering metabolic necessities throughout
the body. Conversely, an understanding of vascular dysfunction has provided
insight into the pathogenesis and progression of diseases both common and rare.
Recent advances in stem cell-based regenerative medicine - including advances in
stem cell technologies and related progress in bioscaffold design and complex
tissue engineering - have allowed rapid advances in the field of vascular
biology, leading in turn to more advanced modeling of vascular pathophysiology
and improved engineering of vascularized tissue constructs. In this review we
examine recent advances in the field of stem cell-derived vasculature, providing
an overview of stem cell technologies as a source for vascular cell types and
then focusing on their use in three primary areas: studies of vascular
development and angiogenesis, improved disease modeling, and the engineering of
vascularized constructs for tissue-level modeling and cell-based therapies.
PMID- 26427874
TI - Expression pattern of sonic hedgehog signaling and calcitonin gene-related
peptide in the socket healing process after tooth extraction.
AB - Sonic Hedgehog (SHH), a neural development inducer, plays a significant role in
the bone healing process. Calcitonin gene-related peptide (CGRP), a neuropeptide
marker of sensory nerves, has been demonstrated to affect bone formation. The
roles of SHH signaling and CGRP-positive sensory nerves in the alveolar bone
formation process have been unknown. Here we examined the expression patterns of
SHH signaling and CGRP in mouse socket by immunohistochemistry and
immunofluorescence analysis. We found that the expression level of SHH peaked at
day 3 and was then decreased at 5 days after tooth extraction. CGRP, PTCH1 and
GLI2 were each expressed in a similar pattern with their highest expression
levels at day 5 and day 7 after tooth extraction. CGRP and GLI2 were co-expressed
in some inflammatory cells and bone forming cells. In some areas, CGRP-positive
neurons expressed GLI2. In conclusion, SHH may affect alveolar bone healing by
interacting with CGRP-positive sensory neurons and thus regulate the socket's
healing process after tooth extraction.
PMID- 26427875
TI - Ex vivo genome-wide RNAi screening of the Drosophila Toll signaling pathway
elicited by a larva-derived tissue extract.
AB - Damage-associated molecular patterns (DAMPs), so-called "danger signals," play
important roles in host defense and pathophysiology in mammals and insects. In
Drosophila, the Toll pathway confers damage responses during bacterial infection
and improper cell-fate control. However, the intrinsic ligands and signaling
mechanisms that potentiate innate immune responses remain unknown. Here, we
demonstrate that a Drosophila larva-derived tissue extract strongly elicits Toll
pathway activation via the Toll receptor. Using this extract, we performed ex
vivo genome-wide RNAi screening in Drosophila cultured cells, and identified
several signaling factors that are required for host defense and antimicrobial
peptide expression in Drosophila adults. These results suggest that our larva
derived tissue extract contains active ingredients that mediate Toll pathway
activation, and the screening data will shed light on the mechanisms of damage
related Toll pathway signaling in Drosophila.
PMID- 26427876
TI - Caenorhabditis elegans ATAD-3 modulates mitochondrial iron and heme homeostasis.
AB - ATAD3 (ATPase family AAA domain-containing protein 3) is a mitochondrial protein,
which is essential for cell viability and organismal development. ATAD3 has been
implicated in several important cellular processes such as apoptosis regulation,
respiratory chain function and steroid hormone biosynthesis. Moreover, altered
expression of ATAD3 has been associated with several types of cancer. However,
the exact mechanisms underlying ATAD3 effects on cellular metabolism remain
largely unclear. Here, we demonstrate that Caenorhabditis elegans ATAD-3 is
involved in mitochondrial iron and heme homeostasis. Knockdown of atad-3 caused
mitochondrial iron- and heme accumulation. This was paralleled by changes in the
expression levels of several iron- and heme-regulatory genes as well as an
increased heme uptake. In conclusion, our data indicate a regulatory role of C.
elegans ATAD-3 in mitochondrial iron and heme metabolism.
PMID- 26427877
TI - Availability of primary care team members can improve teamwork and readiness for
change.
AB - BACKGROUND: Early experiences of patient-centered medical home implementation
indicate that redesigning primary care is an intensive organizational change that
is most effectively undertaken by high-functioning interdisciplinary teams. Team
effectiveness research indicates that consistent availability of team members and
other aspects of team structure can impact teamwork and organizational outcomes.
METHODS: We conducted a survey of 766 adult primary care providers and staff in
34 California safety net practices to assess primary care team structure (team
size, team member availability, and access to interdisciplinary expertise),
teamwork, and readiness for change. We used path models with robust standard
errors for clustering of respondents within practices to examine relationships
between team member availability and readiness for change. Using path analysis,
we examined the extent to which better teamwork mediated relationships between
team member availability and readiness for change. RESULTS: We received 628
completed surveys (response rate = 82%). Greater team member availability was
associated with greater readiness for change, but the relationship was stronger
for staff than for primary care providers. Contrary to our hypothesis, path
analyses revealed that the relationship of team member availability and greater
readiness for change was only partially mediated (21%) by better teamwork. The
direct effect of teamwork on readiness for change is approximately 2.9 times
larger than the direct effect of team member availability on greater readiness
for change. CONCLUSIONS: Ensuring that members perceive that their teammates are
routinely available to them may improve readiness for implementing organizational
changes like adopting patient-centered medical home models. Given that better
teamwork only partially explained the availability-readiness relationship,
additional research to identify the mechanisms through which consistent team
member availability increases change readiness could lend insight into how to
more effectively support clinicians and staff undergoing complex organizational
changes.
PMID- 26427878
TI - Oral fungal immunomodulatory protein-Flammulina velutipes has influence on
pulmonary inflammatory process and potential treatment for allergic airway
disease: A mouse model.
AB - BACKGROUND/PURPOSE: House dust mite (HDM) is well known as one of the major
indoor allergens that trigger allergic inflammation, especially asthma, and
accounts for 85% of all cases. So far, asthma has been thought of as a condition
of imbalance between T helper (Th)1 and Th2. Fungal immunomodulatory protein
Flammulina velutipes (FIP-fve) has been seemingly demonstrated to modulate the
response to Th1 cytokine production. The aim of this study was to investigate if
the oral administration of FIP-fve can inhibit HDM-induced asthma inflammation in
the mouse model. METHODS: We divided the mice (female BALB/c, 4-6 weeks) into
four groups: the prevention group, which consisted of mice sensitized by HDM
(intraperitoneally on Day 1, Day 7, and Day 14, and intranasally on Day 14, Day
17, Day 21, Day 24, and Day 27) fed with FIP-fve from Day 1 to Day 14; the
treatment group, which comprised mice that received treatment from Day 14 to Day
28; the positive control (PC, sensitized by HDM fed without FIP-fve) group; and
the negative control group (NC, nonsensitized). Airway hyperresponsiveness
induced by methacholine challenge was determined using whole-body barometric
plethysmography. In addition, cytokines were analyzed from bronchoalveolar lavage
fluid and serum. Histopathological studies and Liu's staining method in mice
lungs were also performed. RESULTS: The results showed that both pre- and
posttreated FIP-fve groups had significantly reduced airway hyperresponsiveness
compared with the PC group after methacholine challenge. In addition, a
significantly decreased level of HDM-specific immunoglobulin E in serum and
decreased production of Th2 cytokines in bronchoalveolar lavage fluid and serum
were observed in these two FIP-fve fed groups. Moreover, more decreased amounts
of infiltrating inflammatory cells were present in the lungs of FIP-fve fed
groups than those of the PC group. CONCLUSION: Oral FIP-fve had an anti
inflammatory effect on the acute phase of the airway inflammatory process induced
by HDM in the mouse model and might have a potentially therapeutic role for
allergic airway diseases.
PMID- 26427879
TI - DNA adenine methylation modulates pathogenicity of Klebsiella pneumoniae genotype
K1.
AB - BACKGROUND/PURPOSE: Klebsiella pneumoniae genotype K1 is a highly virulent
pathogen that causes liver abscess and metastatic endophthalmitis/meningitis.
Whether its pathogenicity is controlled by DNA adenine methylase (Dam), an
epigenetic regulator of bacterial virulence gene expression, is yet unknown. We
aimed to study the role of DNA adenine methylation in the pathogenicity of K.
pneumoniae genotype K1. METHODS: We identified the dam gene in the prototype
tissue-invasive strain (NTUH-K2044) of K. pneumoniae genotype K1, using the
strain's complete genome sequence in GenBank. We constructed a dam- mutant and
compared it with the wild type, in terms of in vitro serum resistance and in vivo
BALB/cByl mice inoculation. RESULTS: Loss of Dam activity in the mutant was
verified by MboI restriction digestion of the genomic DNA and a 1000-fold
increase in spontaneous mutation rate. The dam mutant lost at least 68% of serum
resistance when compared with the wild type (survival ratio at 1 hour: 2.6 +/-
0.4 vs. 8.2 +/- 1.9; at 2 hours: 3.9 +/- 1.6 vs. 17.4 +/- 3.6; p values < 0.05).
Likewise, virulence to mice decreased by 40-fold in an intraperitoneal injection
model [lethal dose, 50% (LD50): 2 * 103 colony-forming units (CFUs) vs. 5 * 101
CFUs] and by sixfold in a gastric ingestion model (LD50: 3 * 104 CFUs vs. 5 * 103
CFUs). Attenuation of the dam mutant was not attributable to its growth rate,
which was similar to that of the wild type. CONCLUSION: Our results support the
view that DNA adenine methylation plays an important role in modulating the
pathogenicity of K. pneumoniae genotype K1. The incomplete attenuation indicates
the existence of other regulatory factors.
PMID- 26427880
TI - Toxic effect of high concentration of sonochemically synthesized
polyvinylpyrrolidone-coated silver nanoparticles on Citrobacter sp. A1 and
Enterococcus sp. C1.
AB - BACKGROUND/PURPOSE: Currently, silver nanoparticles (AgNPs) have gained
importance in various industrial applications. However, their impact upon release
into the environment on microorganisms remains unclear. The aim of this study was
to analyze the effect of polyvinylpyrrolidone-capped AgNPs synthesized in this
laboratory on two bacterial strains isolated from the environment, Gram-negative
Citrobacter sp. A1 and Gram-positive Enterococcus sp. C1. METHODS:
Polyvinylpyrrolidone-capped AgNPs were synthesized by ultrasound-assisted
chemical reduction. Characterization of the AgNPs involved UV-visible
spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction,
transmission electron microscopy, and energy dispersive X-ray spectroscopy.
Citrobacter sp. A1 and Enterococcus sp. C1 were exposed to varying concentrations
of AgNPs, and cell viability was determined. Scanning electron microscopy was
performed to evaluate the morphological alteration of both species upon exposure
to AgNPs at 1000 mg/L. RESULTS: The synthesized AgNPs were spherical in shape,
with an average particle size of 15 nm. The AgNPs had different but prominent
effects on either Citrobacter sp. A1 or Enterococcus sp. C1. At an AgNP
concentration of 1000 mg/L, Citrobacter sp. A1 retained viability for 6 hours,
while Enterococcus sp. C1 retained viability only for 3 hours. Citrobacter sp. A1
appeared to be more resistant to AgNPs than Enterococcus sp. C1. The cell wall of
both strains was found to be morphologically altered at that concentration.
CONCLUSION: Minute and spherical AgNPs significantly affected the viability of
the two bacterial strains selected from the environment. Enterococcus sp. C1 was
more vulnerable to AgNPs, probably due to its cell wall architecture and the
absence of silver resistance-related genes.
PMID- 26427881
TI - RNA modification enzymes encoded by the gid operon: Implications in biology and
virulence of bacteria.
AB - Ribonucleic acid (RNA) molecules consist of numerous chemically modified
nucleosides that are highly conserved in eukarya, archeae, and bacteria, while
others are unique to each domain of life. In bacteria, hundreds of RNA
modification enzymes have been identified and implicated in biological pathways
associated with many cell processes. The glucose-inhibited division (gid) operon
encodes genes for two RNA modification enzymes named GidA and GidB. Studies have
shown GidA is essential for the proper biosynthesis of 5-methylaminomethyl-2
thiouridine (mnm(5)s(2)U) of bacterial transfer RNA (tRNA) with GidB responsible
for the methylation of the 16S ribosomal RNA (rRNA). Furthermore, deletion of
gidA and gidB has shown to alter numerous bacterial properties like virulence,
stress response, morphology, growth, antibiotic susceptibility, and others. In
this review, we discuss the present knowledge of the RNA modification enzymes
GidA and GidB, and their potential role in the biology and virulence of bacteria.
PMID- 26427882
TI - Antibacterial effect of porcine PTX3 against Streptococcus suis type 2 infection.
AB - Pentraxin 3 (PTX3), a soluble pattern recognition receptor, plays an important
role in innate immunity and has been implicated to be a candidate resistance gene
against Streptococcus suis 2 infection. To discover the antibacterial effect of
porcine PTX3 against S. suis 2, the 42-kDa PTX3 protein was expressed by Chinese
hamster ovary cells (CHO), and an additional eukaryotic expression vector pVAX
ptx3 was constructed. The expressed porcine PTX3 mediated a range of
antibacterial activities including increasing phagocytic capacity of primary
porcine alveolar macrophages (PAM) against S. suis 2 and inhibiting adhesion of
S. suis 2 to human epidermoid cancer cells (Hep-2). In mouse model, pre
intramuscular injecting with pVAX-ptx3 reduced mortality and reduced bacteria
loads in blood, spleen, lung and brain compared with that of control group during
2-12 h following intraperitoneal injection (i.p.) with S. suis 2. Meanwhile, the
expressions of IL-6 and IL-8 in blood were increased in pVAX-ptx3 group, whereas
no obvious changes about IL-10. In piglet model, bacteria load in blood of pVAX
ptx3 group was significantly lower than that of control group after i.p. with S.
suis 2, correspondingly, expression of IL-6 and IL-8 were significantly increased
in pVAX-ptx3 group. In contrast, white blood cell (WBC) and neutrophil cell (NEU)
count of peripheral blood in pVAX-ptx3 group were lower than that of control
group. These studies described a novel antibacterial role for porcine PTX3
against S. suis 2 both in vitro and in vivo and suggested that porcine PTX3 may
be a potential biological agent against S. suis 2 in pig and be used for the
clinical prevention and treatment of streptococcosis caused by S. suis 2.
PMID- 26427883
TI - NOX4-dependent Hydrogen peroxide promotes shear stress-induced SHP2 sulfenylation
and eNOS activation.
AB - Laminar shear stress (LSS) triggers signals that ultimately result in
atheroprotection and vasodilatation. Early responses are related to the
activation of specific signaling cascades. We investigated the participation of
redox-mediated modifications and in particular the role of hydrogen peroxide
(H2O2) in the sulfenylation of redox-sensitive phosphatases. Exposure of vascular
endothelial cells to short periods of LSS (12 dyn/cm(2)) resulted in the
generation of superoxide radical anion as detected by the formation of 2
hydroxyethidium by HPLC and its subsequent conversion to H2O2, which was
corroborated by the increase in the fluorescence of the specific peroxide sensor
HyPer. By using biotinylated dimedone we detected increased total protein
sulfenylation in the bovine proteome, which was dependent on NADPH oxidase 4
(NOX4)-mediated generation of peroxide. Mass spectrometry analysis allowed us to
identify the phosphatase SHP2 as a protein susceptible to sulfenylation under
LSS. Given the dependence of FAK activity on SHP2 function, we explored the role
of FAK under LSS conditions. FAK activation and subsequent endothelial NO
synthase (eNOS) phosphorylation were promoted by LSS and both processes were
dependent on NOX4, as demonstrated in lung endothelial cells isolated from NOX4
null mice. These results support the idea that LSS elicits redox-sensitive signal
transduction responses involving NOX4-dependent generation of hydrogen peroxide,
SHP2 sulfenylation, and ulterior FAK-mediated eNOS activation.
PMID- 26427884
TI - Methamphetamine oxidative stress, neurotoxicity, and functional deficits are
modulated by nuclear factor-E2-related factor 2.
AB - Activation of redox-sensitive transcription factors like nuclear factor-E2
related factor 2 (Nrf2) can enhance the transcription of cytoprotective genes
during oxidative stress. We investigated whether Nrf2 is activated by
methamphetamine (METH) thereby altering neurotoxicity in Nrf2 +/+ and -/- adult
mouse brain. A single dose of METH can induce the mRNA levels of Nrf2-regulated
antioxidant and cytoprotective proteins in mouse brain. Multiple-day dosing with
METH enhanced DNA oxidation and decreased tyrosine hydroxylase and dopamine
transporter staining in the striatum, indicating dopaminergic nerve terminal
toxicity, which was more severe in -/- mice, as were deficits in motor
coordination and olfactory discrimination. These Nrf2-dependent effects were
independent of changes in METH metabolism or the induction of hyperthermia.
Similarly, METH increased striatal glial fibrillary acidic protein, indicating
neurotoxicity. METH neurotoxicity was also observed in the glial cells and in the
GABAergic system of the olfactory bulbs and was enhanced in -/- mice, whereas
dopaminergic parameters were unaffected. With one-day dosing of METH, there were
no differences between +/+ and -/- mice in either basal or METH-enhanced DNA
oxidation and neurotoxicity markers. Nrf2-mediated pathways accordingly may
protect against the neurodegenerative effects and functional deficits initiated
by METH and perhaps other reactive oxygen species-enhancing neurotoxicants, when
there is time for transcriptional activation and protein induction. In human
users of METH, this mechanism may be essential when differences in drug abuse
patterns may alter the induction and duration of Nrf2 activation thereby
modulating susceptibility to the neurotoxic effects of METH.
PMID- 26427885
TI - Miro1-mediated mitochondrial dysfunction under high nutrient stress is linked to
NOD-like receptor 3 (NLRP3)-dependent inflammatory responses in rat pancreatic
beta cells.
AB - Type 2 Diabetes (T2D) is associated with a state of low-grade inflammation that
leads to insulin resistance under sustained high-fat and glucose (HFG) stress.
Mitochondria from pancreatic beta cells play an essential role by metabolizing
nutrients and generating signals required for both triggering and amplifying
pathways of insulin secretion responding to HFG. However, the underlying pathway
linking mitochondrial function to initiate and integrate inflammatory responses
within the pancreatic beta cells under HFG stress remains poorly defined. Here,
we demonstrated that HFG induced Ca(2+)-mediated deleterious effects on
mitochondrial rho GTPase 1 (Miro1), a protein allowing mitochondria to move along
microtubules to regulate mitochondria dynamics. This redistribution of Miro1 by
HFG led to aggravation of proinflammatory responses in rat islets due to damaged
mitochondria-producing reactive oxygen species (ROS). In addition, HFG-induced
Ca(2+)-mediated increased expression of mitochondrial dynamin-like protein (DLP1)
was assembled on the outer membrane of mitochondria to initiate fission events.
Higher expression of DLP1 induced mitochondria fragmentation as expected but was
not essential for ROS-induced proinflammatory responses, while Miro1-mediated
mitochondrial dysfunction induced proinflammatory responses under HFG stress.
Combined, we proposed in this study that HFG stress caused mtROS release mainly
through Miro1-mediated effects on mitochondria in pancreatic beta cells
triggering the NLRP3-dependent proinflammatory responses and, subsequently,
damaged insulin secretion.
PMID- 26427886
TI - Conditional and indirect effects of age of first exposure on PTSD symptoms.
AB - Childhood violence exposure (CVE) in formative developmental years may have
potent effects on severity and complexity of post-traumatic stress symptoms
(PTSS) in adulthood, yet little research has examined the role of age of first
exposure in the context of polyvictimization or gone beyond an examination of
direct effects. The current study examines the specific associations between age
of first exposure, total CVE, and posttraumatic stress symptoms in adulthood.
Further, the conditional and indirect effects of age of first exposure on
posttraumatic stress symptoms were examined. We hypothesized that age of first
exposure to violence would be associated with higher total violence exposure
across childhood, thereby predicting current posttraumatic stress symptom
severity (i.e., indirect effect). We also postulated that age of first exposure
would affect the relationship between total violence exposure and posttraumatic
stress symptoms such that earlier exposure would exacerbate the effects of
violence exposure (i.e., conditional effect). Participants included 269 violence
exposed adults recruited through MTurk; the mean age of first CVE was 6 years
(SD=3.29). Conditional process models indicated that age of first exposure was
significantly associated with higher total childhood violence exposure, which in
turn, was significantly associated with current posttraumatic stress symptoms in
all domains. Further, a conditional effect of age of first exposure was present
such that the relationship between total exposure to violence and symptoms of
hyperarousal was stronger for those first exposed at earlier ages. Findings
provide support suggesting the particular potency of early trauma on regulatory
response systems.
PMID- 26427887
TI - Community-based surveillance to monitor trends in unaccompanied and separated
children in eastern DRC.
AB - Children who are separated from their families and usual caregivers in
emergencies face a multitude of risks. The humanitarian community lacks methods
to systematically capture changes in the frequency and nature of such separations
over time. A mobile phone-based community surveillance system was piloted in the
Democratic Republic of the Congo. The goal was to identify new cases of
unaccompanied and separated children on a weekly basis. Over an 11-week period,
community focal points reported 62 cases of separation across 10 communities. The
majority of children had been under the care of their parents prior to
separation. More than half of the children were unaccompanied, meaning that they
were living without an adult relative or customary caregiver. The pilot results
suggest that implementing a mobile phone-based surveillance system in a
humanitarian setting may be feasible and cost-effective and fills a critical gap
in the measurement of separated and unaccompanied children in emergencies. A
longer pilot to better understand how the system performs over time is
recommended.
PMID- 26427888
TI - Speciation, stability, and coagulation mechanisms of hydroxyl aluminum clusters
formed by PACl and alum: A critical review.
AB - The physicochemical property of coagulant species plays a significant role in the
coagulation process. Recent progress on speciation, stability, and coagulation
mechanisms of the hydroxyl aluminum clusters formed by PACl and alum has been
critically reviewed. The complicated nature on species formation, stability, and
transformation of various hydrolyzed aluminum clusters formed by PACl and Alum
are discussed. Based on the aspects of spontaneous hydrolysis, forced hydrolysis,
and dual-hydrolysis models, the special stability of aluminum clusters that
results in various coagulation behaviors is compared with the traditional salts.
The coagulation behavior of the hydroxyl aluminum clusters in terms of particle
aggregation and restabilization, surface adsorption and coverage, microfloc
formation and kinetics, modified DLVO simulation, and finally, the coagulation
model is then analyzed in detail. It is indicative that the coagulation mechanism
of inorganic coagulants can be understood better with the hydroxyl clusters being
tailor-made.
PMID- 26427889
TI - Short-term effects of lunch on children's executive cognitive functioning: The
randomized crossover Cognition Intervention Study Dortmund PLUS (CogniDo PLUS).
AB - OBJECTIVE: Studies indicate that eating lunch impairs some aspects of adults'
cognitive functioning. However, the short-term effects of lunch on children's
executive functions (EF) have not been examined. The Cognition Intervention Study
Dortmund PLUS (CogniDo PLUS) investigated (a) short-term effects of lunch on EF
in children and (b) whether the postprandial cortisol increase mediates putative
lunch effects on EF performance. METHODS: 5th and 6th grade students of a
comprehensive school in Gelsenkirchen (Germany) participated in the randomized
crossover intervention study. On Day 1 of the study, Group 1 did not eat
lunch,whereas Group 2 received lunch ad libitum. One week later on Day 2 the
groups were treated vice versa. At the beginning of the afternoon lessons, the EF
parameters task switching,working memory updating and inhibition were tested
using a computerized test battery. Saliva samples were used to measure cortisol
directly before lunch and again at the beginning of the cognitive assessment. Of
the 215 initially recruited children 21 dropped out of the study due to illness
or absence on one of the two test days. RESULTS: Lower ratios of false alarms in
the working memory updating function were observed when children who ate lunch
than for children who had no lunch (8.2% (lunch) versus 9.4% (no lunch), p b
0.01). Parameters of task switching and inhibition did not differ between
children who ate lunch compared to children who had no lunch. Stratification
according to postprandial cortisol increase showed that the subgroup with a high
increase had lower ratios of false alarms after eating lunch, while false alarm
values did not change in the group with a low increase. CONCLUSION: In contrast
to findings in adults, the results indicate that children's EF are not impaired
by lunch under true-to-life conditions. On the contrary, the current study even
indicates beneficial effects of lunch intake for the working memory updating. The
postprandial cortisol increase in the range observed in our sample does not seem
to be related with negative effects on the performance of EF, but even seem to
mediate the beneficial effect of lunch on the working memory updating.
PMID- 26427890
TI - The clinical characteristics and treatment of cerebral AVM in pregnancy.
AB - Cerebral arteriovenous malformation (AVM) in pregnancy is a complex situation and
there is no agreement on its hemorrhage risk and treatment. Although studies on
bleeding risk of cerebral AVMs in pregnancy are very few and there are different
results between them, pregnancy will increase the hemorrhagic risk of AVM, and
ruptured cerebral AVM in pregnancy should be treated actively. After intracranial
hemorrhage, cerebral angiography should be performed for pregnant women shielded
correctly. Cerebral angiography could clearly demonstrate the characteristics of
cerebral AVM. The results from the literature show that the radiation dose of
endovascular and stereotactic radiotherapy for cerebral AVM in pregnancy is below
the safety value and is safe. Unruptured AVM in pregnancy, if there is no
bleeding factor, such as no coexisting aneurysm, smooth venous drainage, no
venous ectasia, or high risk of treatment, should be observed conservatively.
PMID- 26427891
TI - Final infarct volume discriminates outcome in mild strokes.
AB - INTRODUCTION: Knowledge of whether final infarct volume (FIV) predicts disability
after mild stroke is limited. We sought to determine if FIV could differentiate
good versus poor outcome after mild stroke. METHODS: We retrospectively
identified 65 patients with mild stroke (National Institutes of Health Stroke
Scale<=5) in a multicenter registry of 2453 patients. We evaluated associations
between FIV and clinical outcome and evaluated the optimal FIV threshold that
discriminated favorable (modified Rankin scale (mRS) 0-1) versus poor (mRS 2-6)
outcome. RESULTS: The FIV cut-point of 20 mL differentiated favorable and poor
outcomes (area under curve (AUC) 0.73, 95% confidence interval: 0.58-0.88).
Favorable outcome was observed in 37/45 (82%) with FIV<20 mL, compared to 5/14
(36%) with FIV>=20 mL (p<0.01). FIV>=20 mL remained strongly associated with poor
outcome independent of age, gender, stroke severity, Alberta Stroke Program Early
CT Score (ASPECTS), and proximal arterial occlusion. CONCLUSION: In our small
sample size, an FIV of 20 mL best differentiated between the likelihood of good
versus poor outcome in patients with mild stroke. Further validation of infarct
volume as a surrogate marker in mild stroke is warranted.
PMID- 26427892
TI - Accuracy of four-dimensional CT angiography in detection and characterisation of
arteriovenous malformations and dural arteriovenous fistulas.
AB - A retrospective review was made to assess the accuracy of four dimensional CT
angiogram (4D-CTA) in diagnosis of arteriovenous malformations (AVM) and dural
arteriovenous fistulas (DAVF), with catheter-based digital-subtraction angiogram
(DSA) being gold standard. 33 pairs of investigations (DSA and 4D-CTA) were
performed primarily for suspicion of AVM/DAVF. Based on blinded reports,
sensitivity and specificity for detection of AVM/DAVF were 77% (95% CI: 46-95%)
and 100% (95% CI: 83-100%) respectively. Positive predictive value was 100% (95%
CI: 69-100%) and negative predictive value 87% (95% CI: 66-97%). 4D-CTA is a
practical minimally-invasive technique for evaluating cerebrovascular
pathologies. There is good agreement between the findings of 4D-CTA and DSA
despite the differences in temporal and spatial resolutions. 4D-CTA may obviate
the need for DSA in a subgroup of patients who would otherwise have undergone
this invasive investigation, which carries a risk of important complications.
PMID- 26427893
TI - Magnetic resonance imaging findings of two sisters with Van der Knaap
leukoencephalopathy.
AB - Megalencephalic leukoencephalopathy with subcortical cysts, or Van der Knaap
leukoencephalopathy, is a rare disease which is characterised by macrocephaly and
neurological disorders with autosomal recessive inheritance. Magnetic resonance
imaging is very helpful for determining distinctive findings and distinguishing
other diseases. We present the radiological findings of two sisters (aged 6 and
10 years) diagnosed with Van der Knaap leukoencephalopathy.
PMID- 26427894
TI - Automatic brain matter segmentation of computed tomography images using a
statistical model: A tool to gain working time!
AB - Brain computed tomography (CT) is useful diagnostic tool for the evaluation of
several neurological disorders due to its accuracy, reliability, safety and wide
availability. In this field, a potentially interesting research topic is the
automatic segmentation and recognition of medical regions of interest (ROIs).
Herein, we propose a novel automated method, based on the use of the active
appearance model (AAM) for the segmentation of brain matter in CT images to
assist radiologists in the evaluation of the images. The method described, that
was applied to 54 CT images coming from a sample of outpatients affected by
cognitive impairment, enabled us to obtain the generation of a model overlapping
with the original image with quite good precision. Since CT neuroimaging is in
widespread use for detecting neurological disease, including neurodegenerative
conditions, the development of automated tools enabling technicians and
physicians to reduce working time and reach a more accurate diagnosis is needed.
PMID- 26427895
TI - Imaging of skull base pathologies: Role of advanced magnetic resonance imaging
techniques.
AB - Imaging plays a vital role in evaluation of skull base pathologies as this region
is not directly accessible for clinical evaluation. Computerized tomography (CT)
and magnetic resonance imaging (MRI) have played complementary roles in the
diagnosis of the various neoplastic and non-neoplastic lesions of the skull base.
However, CT and conventional MRI may at times be insufficient to correctly
pinpoint the accurate diagnosis. Advanced MRI techniques, though difficult to
apply in the skull base region, in conjunction with CT and conventional MRI can
however help in improving the diagnostic accuracy. This article aims to highlight
the importance of advanced MRI techniques like diffusion-weighted imaging,
susceptibility-weighted imaging, perfusion-weighted imaging, and MR spectroscopy
in differentiation of various lesions involving the skull base.
PMID- 26427896
TI - Contralateral recurrence of tumefactive demyelination.
AB - Tumefactive demyelination refers to large focal demyelinating lesions in the
brain, which can be mistaken for malignancy. In some patients, these lesions are
monophasic with a self-limited course; however, other patients demonstrate
recurrent disease with new tumefactive or non-tumefactive lesions, and a
subsequent diagnosis of relapsing-remitting multiple sclerosis is not uncommon.
Owing to the limited data available in the literature, many questions about the
patterns and prognostic significance of recurrent tumefactive lesions remain
unanswered. The current case report involves a patient who recovered from
tumefactive demyelination and presented two years later with a new recurrent
tumefactive lesion in the contralateral brain.
PMID- 26427898
TI - Bilateral pallidal hemorrhage in toxoplasmosis update of acute symmetric lesions
of deep nuclei.
AB - As acute symmetric lesions of deep gray nuclei are often associated with an
impaired level of consciousness and neuroimaging by itself cannot distinguish
between etiologies, diagnosis may be problematic. Appreciation of the cause of
the various neuroimaging patterns in conjunction with the history, examination
and laboratory investigations allows for accurate diagnosis in the vast majority
of cases. Given the metabolic vulnerability of deep gray nuclei, other than bi
thalamic infarction, it follows that toxic-metabolic and hypoxic-ischemic events
account for the majority of cases. Nevertheless, the differential diagnosis is
broad and diverse. We here describe two cases of bilateral pallidal hemorrhage in
AIDS-associated toxoplasmosis, and review conditions recently described with
acute symmetric deep gray nuclei lesions on neuroimaging.
PMID- 26427897
TI - Neuroimaging evaluation in refractory epilepsy.
AB - PURPOSE: To describe the application of neuroimaging analysis, compared to
neuropsychological tests and video-electroencephalogram, for the evaluation of
refractory epilepsy in a reference centre in Cali, Colombia. METHODS: Between
March 2013 and November 2014, 29 patients, 19 men and 10 women, aged 9-65 years
and with refractory epilepsy, were assessed by structural and functional magnetic
resonance imaging while performing tasks related to language, verbal and non
verbal memory. Also, volumetric evaluation was performed. A 1.5 Tesla magnetic
resonance imaging scanner was used in all cases. RESULTS: Neuroimaging evaluation
identified 13 patients with mesial temporal sclerosis. The remaining patients
were classified as: 10 patients with neoplastic masses, two patients with
cortical atrophy, two patients with scarring lesions and two patients with non
structural aetiology. Among patients with mesial temporal sclerosis, comparison
between techniques for lateralising the epileptogenic foci was made; the kappa
index between functional magnetic resonance imaging and hippocampi volumetry was
kappa=1.00, agreement between neuroimaging and video-electroencephalogram was
good (kappa=0.78) and comparison with a neuropsychological test was mild
(kappa=0.24). CONCLUSIONS: Neuroimaging studies allow the assessment of
functional and structural damage related to epileptogenic lesions and foci, and
are helpful to select surgical treatment, conduct intraoperative neuronavigation
techniques, predict surgical deficits and evaluate patient recovery.
PMID- 26427899
TI - All patients with HIV should get access to drug treatments regardless of CD4
count, says WHO.
PMID- 26427901
TI - Women's healthcare: initiatives and challenges.
AB - John C Jennings is 2014-2015 President of the American College and Congress of
Obstetricians and Gynecologists. He is currently Professor of Obstetrics and
Gynecology at Texas Tech University Health Sciences Center and has previously
served as Regional Dean of the School of Medicine at TTUHSC Permian Basin. He is
a passionate medical educator and during his academic career he has served as
division chief, residency program director and department chair. He has authored
numerous peer-reviewed and other publications and has been the recipient of
multiple teaching awards. Prior to entering academic medicine, he was a busy
practicing obstetrician/gynecologist in San Angelo, TX, USA.
PMID- 26427902
TI - Gluteal muscle fatty atrophy is not associated with elevated blood metal ions or
pseudotumors in patients with a unilateral metal-on-metal hip replacement.
AB - BACKGROUND AND PURPOSE: There are no international guidelines to define adverse
reaction to metal debris (ARMD). Muscle fatty atrophy has been reported to be
common in patients with failing metal-on-metal (MoM) hip replacements. We
assessed whether gluteal muscle fatty atrophy is associated with elevated blood
metal ion levels and pseudotumors. PATIENTS AND METHODS: 263 consecutive patients
with unilateral ASR XL total hip replacement using a posterior approach and with
an unoperated contralateral hip were included in the study. All patients had
undergone a standard screening program at our institution, including MRI and
blood metal ion measurement. Muscle fatty atrophy was graded as being absent,
mild, moderate, or severe in each of the gluteal muscles. RESULTS: The prevalence
of moderate-to-severe gluteal muscle atrophy was low (12% for gluteus minimus,
10% for gluteus medius, and 2% for gluteus maximus). Muscle atrophy was neither
associated with elevated blood metal ion levels (> 5 ppb) nor with the presence
of a clear (solid- or mixed-type) pseudotumor seen in MRI. A combination of
moderate-to-severe atrophy in MRI, elevated blood metal ion levels, and MRI
confirmed mixed or solid pseudotumor was rare. Multivariable regression revealed
that "preoperative diagnosis other than osteoarthrosis" was the strongest
predictor of the presence of fatty atrophy. INTERPRETATION: Gluteal muscle
atrophy may be a clinically significant finding with influence on hip muscle
strength in patients with MoM hip replacement. However, our results suggest that
gluteal muscle atrophy seen in MRI is not associated with either the presence or
severity of ARMD, at least not in patients who have been operated on using the
posterior approach.
PMID- 26427905
TI - Community pharmacy and emerging public health initiatives in developing Southeast
Asian countries: a systematic review.
AB - The development of health and healthcare systems in South-East Asia has
influenced the practice of community pharmacy. Over the years, community pharmacy
in the region has striven to expand services beyond dispensing to encompass more
involvement in public health issues. Searches were conducted in Scopus, EMBASE,
MEDLINE and PubMed for articles published between January 2000 and December 2014,
with 21 studies in five countries meeting the inclusion criteria. The findings
showed increasing interest in research into the delivery of pharmacy services and
public health initiatives. Overall, the review found that provision of some
health services in pharmacies was common; however, most public health initiatives
appeared to be poorly implemented, had limited evidence and were not demonstrated
to be sustainable across the sector. This indicates that the practice of
community pharmacy in the region has not significantly changed over the past 14
years with respect to the scope and quality of pharmacy services provided, and
fundamental policy changes are necessary to improve this situation.
PMID- 26427904
TI - Orthostatic hypotension: managing a difficult problem.
AB - Orthostatic hypotension (OH) leads to a significant number of hospitalizations
each year, and is associated with significant morbidity and mortality among
affected individuals. Given the increased risk for cardiovascular events and
falls, it is important to identify the underlying etiology of OH and to choose
appropriate therapeutic agents. OH can be non-neurogenic or neurogenic (arising
from a central or peripheral lesion). The initial evaluation includes orthostatic
vital signs, complete history and a physical examination. Patients should also be
evaluated for concomitant symptoms of post-prandial hypotension and supine
hypertension. Non-pharmacologic interventions are the first step for treatment of
OH. The appropriate selection of medications can also help with symptomatic
relief. This review highlights the pathophysiology, clinical features, diagnostic
work-up and treatment of patients with neurogenic OH.
PMID- 26427906
TI - Gating by tryptophan 73 exposes a cryptic pocket at the protein-binding interface
of the oncogenic eIF4E protein.
AB - Targeting protein-protein interacting sites for potential therapeutic
applications is a challenge in the development of inhibitors, and this becomes
more difficult when these interfaces are relatively planar, as in the eukaryotic
translation initiation factor 4E (eIF4E) protein. eIF4E is an oncogene that is
overexpressed in numerous forms of cancer, making it a prime target as a
therapeutic molecule. We report here the presence of a cryptic pocket at the
protein-binding interface of eIF4E, which opens transiently during molecular
dynamics simulations of the protein in solvent water and is observed to be stable
when solvent water is mixed with benzene molecules. This pocket can also be seen
in the ensemble of structures available from the solution-state conformations of
eIF4E. The accessibility of the pocket is gated by the side-chain transitions of
an evolutionarily conserved tryptophan residue. It is found to be feasible for
accommodating clusters of benzene molecules, which signify the plasticity and
ligandability of the pocket. We also observe that the newly formed cavity
provides a favorable binding environment for interaction of a well-recognized
small molecule inhibitor of eIF4E. The occurrence of this transiently accessible
cavity highlights the existence of a more pronounced binding groove in a region
that has traditionally been considered to be planar. Together, the data suggest
that an alternate binding cavity exists on eIF4E and could be exploited for the
rational design and development of a new class of lead compounds against the
protein.
PMID- 26427908
TI - Significantly Enhanced Separation using ZIF-8 Membranes by Partial Conversion of
Calcined Layered Double Hydroxide Precursors.
AB - Significantly enhanced H2 /CH4 (ca. 80) selectivity was realized by effective
suppression of the framework flexibility of a prepared ZIF-8 membrane. Initially
a ZnO buffer layer consisting of 20 nm-sized ZnO-nanoparticle aggregates was
fabricated by controlled calcination of a ZnAl-NO3 layered double hydroxide
membrane. Owing to its high chemical reactivity, the ZnO buffer layer was
partially converted into a well-intergrown ZIF-8 membrane with a certain
penetration depth upon solvothermal treatment with ligands. Our method may
represent a new concept for the design of advanced MOF membranes with high
selectivity.
PMID- 26427907
TI - Genetic upregulation of BK channel activity normalizes multiple synaptic and
circuit defects in a mouse model of fragile X syndrome.
AB - KEY POINTS: Single-channel recordings in CA3 pyramidal neurons revealed that
large-conductance calcium-activated K(+) (BK) channel open probability was
reduced by loss of fragile X mental retardation protein (FMRP) and that FMRP acts
on BK channels by modulating the channel's gating kinetics. Fmr1/BKbeta4 double
knockout mice were generated to genetically upregulate BK channel activity in the
absence of FMRP. Deletion of the BKbeta4 subunit alleviated reduced BK channel
open probability via increasing BK channel open frequency, but not through
prolonging its open duration. Genetic upregulation of BK channel activity via
deletion of BKbeta4 normalized action potential duration, excessive glutamate
release and short-term synaptic plasticity during naturalistic stimulus trains in
excitatory hippocampal neurons in the absence of FMRP. Genetic upregulation of BK
channel activity via deletion of BKbeta4 was sufficient to normalize excessive
epileptiform activity in an in vitro model of seizure activity in the hippocampal
circuit in the absence of FMRP. Loss of fragile X mental retardation protein
(FMRP) causes fragile X syndrome (FXS), yet the mechanisms underlying the
pathophysiology of FXS are incompletely understood. Recent studies identified
important new functions of FMRP in regulating neural excitability and synaptic
transmission via both translation-dependent mechanisms and direct interactions of
FMRP with a number of ion channels in the axons and presynaptic terminals. Among
these presynaptic FMRP functions, FMRP interaction with large-conductance calcium
activated K(+) (BK) channels, specifically their auxiliary beta4 subunit,
regulates action potential waveform and glutamate release in hippocampal and
cortical pyramidal neurons. Given the multitude of ion channels and mechanisms
that mediate presynaptic FMRP actions, it remains unclear, however, to what
extent FMRP-BK channel interactions contribute to synaptic and circuit defects in
FXS. To examine this question, we generated Fmr1/beta4 double knockout (dKO) mice
to genetically upregulate BK channel activity in the absence of FMRP and
determine its ability to normalize multilevel defects caused by FMRP loss. Single
channel analyses revealed that FMRP loss reduced BK channel open probability, and
this defect was compensated in dKO mice. Furthermore, dKO mice exhibited
normalized action potential duration, glutamate release and short-term dynamics
during naturalistic stimulus trains in hippocampal pyramidal neurons. BK channel
upregulation was also sufficient to correct excessive seizure susceptibility in
an in vitro model of seizure activity in hippocampal slices. Our studies thus
suggest that upregulation of BK channel activity normalizes multi-level deficits
caused by FMRP loss.
PMID- 26427909
TI - Bioactivites of two common polyphenolic compounds: Verbascoside and catechin.
AB - CONTEXT: Natural products can present remarkable biological and pharmacological
activities. In traditional medicine, plants have been used historically in
treating cancer, infections, and other inflammatory conditions. OBJECTIVE:
Verbascoside and catechin are widespread polyphenolic plant compounds that could
play a role in the anti-inflammatory and health-promoting effects of plants and
plant extracts. MATERIALS AND METHODS: This study compares the potential
cytotoxic effects of polyphenols verbascoside and catechin (6.25-200 uM) on human
peripheral blood mononuclear cells (PBMC) for 48 h and myelomonocytic THP-1 and
THP-1 Blue cells for 24 h. The effects of the compounds on immune activation
markers such as indoleamine 2,3-dioxygenase (IDO) activity as well as on
neopterin formation and nuclear factor-kappaB (NF-kappaB) activation were
investigated. Cytotoxicity of the compounds was tested using Cell-Titer Blue
assay. RESULTS: Verbascoside exhibited significant suppressive effects in mitogen
stimulated PBMC on tryptophan breakdown (>50 uM; IC50 value: 58.6 uM) and the
production of neopterin (>6.25 uM; IC50 value: 217 uM). These effects correlated
with a decline in cell viability, while THP-1 Blue cells were less sensitive. NF
kappaB activity was slightly enhanced at lower concentrations (<50 uM
verbascoside) in stimulated cells and at the highest concentration used in
unstimulated cells. Catechin had no relevant effects on cell viability and on the
tested inflammation markers, except NF-kappaB activation in THP-1 Blue cells.
DISCUSSION AND CONCLUSION: The results obtained show that verbascoside and
catechin represent effective compounds which interfere with immunobiochemical
pathways that are highly relevant for immunosurveillance and competing virus
infections.
PMID- 26427910
TI - Cerebral hemodynamics in orthostatic intolerance with normal head-up tilt test.
AB - OBJECTIVES: Orthostatic hypotension (OH) and postural orthostatic tachycardia
syndrome (POTS) are well-known causes of orthostatic intolerance (OI). In
addition, there are OI patients who are characterized by the symptoms of OI and
lack of abnormal findings in head-up tilt (HUT) test. The aim of this study was
to determine the cerebral hemodynamic changes in HUT test of OI patients with
normal HUT (OINH). MATERIALS AND METHODS: Two hundred and sixty-one OI patients
and 50 healthy controls were enrolled in this study. All subjects underwent
transcranial Doppler test while performing the HUT test. Forty-five patients had
OH, 33 patients had POTS, and 183 patients had OINH. Blood pressures, heart rate,
cerebral blood flow velocities (CBFVs), end-tidal carbon dioxide (ET-PCO2 ),
cerebral critical closing pressure (CCP), cerebral perfusion pressure (CPP), and
cerebral vascular resistance (CVR) were measured during HUT test. We compared the
hemodynamic parameters of OINH with those of OH, POTS, and healthy controls.
RESULTS: Reduced CBFVs, CPP, and ET-PCO2 and elevated CCP were observed in the
HUT test of all four groups. CVR was reduced in three OI patients. The drops in
systolic CBFV, CPP, and CVR of OINH patients were greater than those of healthy
controls. The changes in parameters in the HUT test of OINH group were not
different from those of OH and POTS groups except prominent decrements of CPP and
CVR in OH group. CONCLUSION: Our findings suggest that OINH is true OI sharing
the common pathomechanism of OH and POTS.
PMID- 26427913
TI - The impact of venous occlusion per se on forearm muscle blood flow: implications
for the near-infrared spectroscopy venous occlusion technique.
AB - The purpose of this study was to examine the effect of venous occlusion per se on
forearm muscle blood flow, as determined by the near-infrared spectroscopy (NIRS)
venous occlusion technique (NIRS-VOT). NIRS data were obtained from the flexor
digitorum superficialis (FDS) muscle on the dominant arm of 16 young, ostensibly
healthy participants (14 men and two women; 30 +/- 6 year; 73 +/- 7 kg).
Participants completed a series of five venous occlusion trials while seated at
rest, and a series of 12 venous occlusion trials during a reactive hyperaemia
induced by 5 min of forearm arterial occlusion. The NIRS-VOT was used to assess
FDS muscle blood flow (Qmus), beat-by-beat, over the first four cardiac beats
during venous occlusions. Qmus was also reported as a cumulative value, wherein
the first two, first three and first four cardiac beats were used to calculate
muscle blood flow. We observed that Qmus was highest when calculated over the
first cardiac beat during venous occlusions performed at rest and throughout
reactive hyperaemia (P<0.05). Moreover, the inclusion of more than one cardiac
beat in the calculation of Qmus underestimated muscle blood flows, irrespective
of the prevailing level of arterial inflow. These findings support the idea that
venous occlusion per se affects the measurement of Qmus via the NIRS-VOT.
Accordingly, it is recommended that Qmus is determined over the first cardiac
beat when using the NIRS-VOT to assess microvascular blood flow of human forearm
muscles.
PMID- 26427911
TI - Metal-Free Addition/Head-to-Tail Polymerization of Transient Phosphinoboranes,
RPH-BH2: A Route to Poly(alkylphosphinoboranes).
AB - Mild thermolysis of Lewis base stabilized phosphinoborane monomers R(1)R(2)P
BH2?NMe3 (R(1),R(2)=H, Ph, or tBu/H) at room temperature to 100 degrees C
provides a convenient new route to oligo- and polyphosphinoboranes [R(1)R(2)P
BH2]n. The polymerization appears to proceed via the addition/head-to-tail
polymerization of short-lived free phosphinoborane monomers, R(1)R(2)P-BH2. This
method offers access to high molar mass materials, as exemplified by poly(tert
butylphosphinoborane), that are currently inaccessible using other routes (e.g.
catalytic dehydrocoupling).
PMID- 26427912
TI - Direct and Mediating Effects of an Anxiety Sensitivity Intervention on
Posttraumatic Stress Disorder Symptoms in Trauma-Exposed Individuals.
AB - Anxiety sensitivity (AS), or fear of anxious arousal, is a higher-order cognitive
risk-factor for posttraumatic stress disorder (PTSD) composed of lower-order
physical, cognitive, and social concerns regarding anxiety symptoms. Brief and
effective interventions have been developed targeting AS and its constituent
components. However, there is limited evidence as to whether an intervention
aimed at targeting AS would result in reductions in PTS symptoms and whether the
effects on PTS symptoms would be mediated by reductions in AS. Furthermore, there
is no evidence whether these mediation effects would be because of the global or
more specific components of AS. The direct and indirect effects of an AS
intervention on PTS symptoms were examined in a sample of 82 trauma-exposed
individuals (M age = 18.84 years, SD = 1.50) selected based on elevated AS levels
(i.e., 1 SD above the mean) and assigned to either a treatment (n = 40) or an
active control (n = 42) condition. Results indicated that the intervention led to
reductions in Month 1 PTS symptoms, controlling for baseline PTS symptoms.
Furthermore, this effect was mediated by changes in global AS and AS social
concerns, occurring from intervention to Week 1. These findings provide an
initial support for an AS intervention in amelioration of PTS symptoms and
demonstrate that it is primarily reductions in the higher-order component of AS
contributing to PTS symptom reduction.
PMID- 26427915
TI - Evidence of the late lignification of the G-layer in Simarouba tension wood, to
assist understanding how non-G-layer species produce tensile stress.
AB - To recover verticality after disturbance, angiosperm trees produce 'tension wood'
allowing them to bend actively. The driving force of the tension has been shown
to take place in the G-layer, a specific unlignified layer of the cell wall
observed in most temperate species. However, in tropical rain forests, the G
layer is often absent and the mechanism generating the forces to reorient trees
remains unclear. A study was carried out on tilted seedlings, saplings and adult
Simarouba amara Aubl. trees-a species known to not produce a G-layer. Microscopic
observations were done on sections of normal and tension wood after staining or
observed under UV light to assess the presence/absence of lignin. We showed that
S. amara produces a cell-wall layer with all of the characteristics typical of G
layers, but that this G-layer can be observed only as a temporary stage of the
cell-wall development because it is masked by a late lignification. Being thin
and lignified, tension wood fibres cannot be distinguished from normal wood
fibres in the mature wood of adult trees. These observations indicate that the
mechanism generating the high tensile stress in tension wood is likely to be the
same as that in species with a typical G-layer and also in species where the G
layer cannot be observed in mature cells.
PMID- 26427914
TI - Cancer-related CD15/FUT4 overexpression decreases benefit to agents targeting
EGFR or VEGF acting as a novel RAF-MEK-ERK kinase downstream regulator in
metastatic colorectal cancer.
AB - BACKGROUND: Cancer-related immune antigens in the tumor microenvironment could
represent an obstacle to agents targeting EGFR "cetuximab" or VEGF "bevacizumab"
in metastatic colorectal cancer (mCRC) patients. METHODS: Infiltrating immune
cells into tumor tissues, cancer-related expression of immune antigens (CD3, CD8,
CD68, CD73, MPO, CD15/FUT4) from 102 mCRC patients receiving first-line Cetuximab
or Bevacizumab plus chemotherapy were assessed by immunohistochemistry and
validated in an independent tissue microarrays of 140 patients. Genome-wide
expression profiles from 436 patients and 60 colon cancer cell lines were
investigated using bioinformatics analysis. In vitro kinase assays of target
genes activated by chemokines or growth factors were performed. RESULTS: Here, we
report that cancer-related CD15/FUT4 is overexpressed in most of mCRCs patients
(43 %) and associates with lower intratumoral CD3+ and CD8+ T cells, higher
systemic inflammation (NLR at diagnosis >5) and poorer outcomes, in terms of
response and progression-free survival than those CD15/FUT4-low or negative ones
(adjusted hazard ratio (HR) = 2.92; 95 % CI = 1.86-4.41; P < 0.001).
Overexpression of CD15/FUT4 is induced through RAF-MEK-ERK kinase cascade,
suppressed by MEK inhibitors and exhibits a close connection with constitutive
oncogenic signalling pathways that respond to ERBB3 or FGFR4 activation (P <
0.001). CD15/FUT4-high expressing colon cancer cells with primary resistance to
cetuximab or bevacizumab are significantly more sensitive to MEK inhibitors than
CD15/FUT4-low counterparts. CONCLUSION: Cancer-related CD15/FUT4 overexpression
participates in cetuximab or bevacizumab mechanisms of resistance in mCRC
patients. CD15/FUT4 as a potential target of the antitumor immune response
requires further evaluation in clinical studies.
PMID- 26427916
TI - Towards Organized Hybrid Nanomaterials at the Air/Water Interface Based on Liquid
Crystal/ZnO Nanocrystals.
AB - The ability to self-assemble nanosized ligand-stabilized metal oxide or
semiconductor materials offers an intriguing route to engineer nanomaterials with
new tailored properties from the disparate components. We describe a novel one
pot two-step organometallic approach to prepare ZnO nanocrystals (NCs) coated
with deprotonated 4-(dodecyloxy)benzoic acid (i.e., an X-type liquid-crystalline
ligand) as a model LC system (termed ZnO-LC1 NCs). Langmuir and Langmuir-Blodgett
films of the resulting hybrids are investigated. The observed behavior of the ZnO
NCs at the air/water interface is rationalized by invoking a ZnO-interdigitation
process mediated by the anchored liquid-crystalline shell. The ordered
superstructures form according to mechanism based on a ZnO-interdigitation
process mediated by liquid crystals (termed ZIP-LC). The external and directed
force applied upon compression at the air/water interface and the packing of the
ligands that stabilize the ZnO cores drives the formation of nanorods of ordered
internal structure. To study the process in detail, we follow a nontraditional
protocol of thin-film investigation. We collect the films from the air/water
interface in powder form (ZnO-LC1 LB), resuspend the powder in organic solvents
and utilize otherwise unavailable experimental techniques. The structural and
physical properties of the resulting superlattices were studied by using electron
microscopy, atomic force microscopy, X-ray studies, dynamic light scattering,
thermogravimetric analysis, UV/Vis absorption, and photoluminescence
spectroscopy.
PMID- 26427918
TI - Comparison of people with serious mental illness and general population samples
enrolled in lifestyle interventions for weight loss.
PMID- 26427917
TI - Improving the understanding of the link between cognition and functional capacity
in schizophrenia and bipolar disorder.
AB - OBJECTIVE: Deficits in cognitive functioning are related to functional disability
in people with serious mental illness. Measures of functional capacity are
commonly used as a proxy for functional disabilities for cognitive remediation
programs, and robust linear relationships between functional capacity and
cognitive deficits are frequently observed. This study aimed to determine whether
a curvilinear relationship better approximates the association between cognitive
functioning and functional capacity. METHOD: Two independent samples were
studied. Study 1: participants with schizophrenia (n=435) and bipolar disorder
(n=390) aged 18-83 completed a neuropsychological battery and a performance-based
measure of functional capacity. Study 2: 205 participants with schizophrenia (age
range=39-72) completed a brief neuropsychological screening battery and a
performance-based measure of functional capacity. For both studies, linear and
quadratic curve estimations were conducted with cognitive performance predicting
functional capacity scores. RESULTS: Significant linear and quadratic trends were
observed for both studies. Study 1: in both the schizophrenia and bipolar
participants, when cognitive composite z-scores were >0 (indicating normal to
above normal performance), cognition was not related to functional capacity.
Study 2: when neuropsychological screening battery z-scores were >-1 (indicating
low average to average performance), cognition was not related to functional
capacity. CONCLUSIONS: These results illustrate that in cognitively normal adults
with serious mental illness, the relationship between cognitive function and
functional capacity is relatively weak. These findings may aid clinicians and
researchers determine who may optimally benefit from cognitive remediation
programs, with greater benefits possibly being achieved for individuals with
cognitive deficits relative to individuals with normal cognition.
PMID- 26427919
TI - Risk of Hospital Readmission Among Infants With Neonatal Abstinence Syndrome.
AB - OBJECTIVE: Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal
syndrome that may last for months. Our objective was to determine if infants with
NAS are at increased risk for hospital readmission compared with uncomplicated
term and late preterm newborns. METHODS: In this longitudinal retrospective
cohort study, administrative data were used for all births from 2006 to 2009 in
the New York State Inpatient Database. We identified infants with NAS, born late
preterm or uncomplicated term, as independent groups using diagnostic codes and
determined readmission rates. We fit a multivariable logistic regression model
with 30-day readmission after discharge as the outcome and infant
characteristics, clinical morbidities, insurance type, and length of birth
hospitalization as predictors. RESULTS: From 2006 to 2009 in New York State, 700
613 infants were classified as uncomplicated term, 51 748 were born late preterm,
and 1643 infants were diagnosed with NAS. After adjusting for confounders,
infants with NAS (odds ratio [OR] 2.49, 95% confidence interval [CI] 1.75-3.55)
were more likely than uncomplicated term infants to be readmitted within 30 days
of birth hospitalizations. The risk of readmission was similar to late preterm
infants (OR 2.26, 95% CI 2.09-2.45). Length of birth hospitalization in days was
inversely related to odds of being readmitted within 30 days of birth
hospitalization (OR 0.94 95% CI 0.92-0.96). CONCLUSIONS: When compared with
uncomplicated term infants, infants diagnosed with NAS were more than twice as
likely to be readmitted to the hospital. Future research and state-level policies
should investigate means to mitigate risk of hospital readmission for infants
with NAS.
PMID- 26427920
TI - Clinical Impact of an Antimicrobial Stewardship Program on Pediatric Hospitalist
Practice, a 5-Year Retrospective Analysis.
AB - BACKGROUND AND OBJECTIVES: Hospitalists increasingly serve as the primary
physicians for children hospitalized with infections. Consequently, hospitalists
frequently interact with institutional antimicrobial stewardship programs (ASPs).
Understanding how these services interact can inform ongoing practice improvement
efforts. The objectives of this study were to identify factors associated with
ASP recommendations among hospitalist-managed children, and to determine the
association of ASP interventions with clinical outcomes for hospitalist-managed
patients. METHODS: We retrospectively analyzed ASP reviews of hospitalist
patients from a children's hospital from March 2008 to June 2013. Clinical
factors associated with an ASP recommendation were determined. Length of stay and
30-day readmission were compared between cases of agreement and disagreement with
ASP recommendations. RESULTS: The ASP reviewed 2163 hospitalist patients,
resulting in 350 recommendations (16.2% of reviews). Hospitalists agreed with ASP
recommendations in 86.9% of cases. The odds of an ASP recommendation decreased
during the study period. Ceftriaxone was the most common antibiotic associated
with a recommendation (154/350, 44.0%); community-acquired pneumonia was the most
common diagnosis (105/350, 30.0%). Antibiotic discontinuation was the most often
recommendation; hospitalists most often disagreed with consulting infectious
diseases. Disagreement with ASP recommendations was associated with a decreased
length of stay of 15.4 (95% confidence interval -33.2 to 1.1) hours but not 30
day readmission prevalence. CONCLUSIONS: Pediatric hospitalists and ASPs can form
an effective collaboration that improves antibiotic use while providing safe
care. Better characterization of the areas of disagreement between hospitalists
and ASPs is needed. Future studies are needed to identify ASP strategies that
will be beneficial in other hospitalist settings.
PMID- 26427921
TI - Management of Hospitalized Febrile Neonates Without CSF Analysis: A Study of US
Pediatric Hospitals.
AB - OBJECTIVE: Management of febrile neonates includes obtaining blood, urine, and
cerebrospinal fluid (CSF) cultures with hospitalization for empiric parenteral
antibiotic therapy. Outcomes and management for neonates were compared based on
whether CSF was obtained. METHODS: This multicenter retrospective review of the
2002 to 2012 Pediatric Health Information System database included hospitalized
infants aged <=28 days (neonates) admitted to an inpatient ward with a diagnosis
code for fever or neonatal fever. Patients admitted to an ICU or with a complex
chronic condition diagnosis code were excluded. Neonates were categorized as full
septic workup (FSW; charge codes for blood, urine, and CSF culture or cell count)
or as partial septic workup (PSW; charge codes for blood and urine cultures
only), and their data were compared. RESULTS: Of 27 480 neonates with a diagnosis
code for fever, 14 774 underwent the FSW and 3254 had a PSW. Median length of
stay was 2 days for both groups, with no significant difference in readmissions,
disposition, or parenteral antibiotic administration. Neonates with a PSW had
significantly greater odds of having charge codes for additional laboratory
testing and imaging, and they were more likely to receive a diagnosis code for
sepsis, meningitis, or bronchiolitis. CONCLUSIONS: Neonates with PSW had lengths
of stay and readmission rates similar to those with FSW but were more likely to
undergo additional laboratory testing and imaging. Future studies including
information about clinical severity and test results may provide additional
insight into the variation in practice for this patient population.
PMID- 26427922
TI - A Brief Inpatient Intervention Using a Short Video to Promote Reduction of Child
Tobacco Smoke Exposure.
AB - OBJECTIVES: Tobacco smoke exposure (TSE) increases the risk for respiratory
related disease and hospitalizations. The hypothesis of this study was that a
brief intervention (which included a motivational video) provided to parents and
caregivers during their child's hospitalization would be associated with improved
knowledge and behavior changes that may reduce the child's TSE. METHODS: Parents
and caregivers of children hospitalized for respiratory illnesses with TSE were
recruited between June and December 2012. They completed a questionnaire to
determine baseline knowledge regarding the health effects of smoke exposure. The
intervention included a motivational video, written smoking cessation materials,
and referral to the state quitline. The questionnaire was repeated after the
intervention; telephone follow-up at 1 and 3 months included knowledge questions
and assessed behavior changes. Paired t tests were used to compare
preintervention and postintervention knowledge scores. RESULTS: A total of 167
parents/caregivers were enrolled. The mean preintervention knowledge score was
high at 5.4 of 6, which improved for 60 parents/caregivers (36%, P < .001) after
the intervention and was sustained at follow-up. Follow-up was obtained from 123
(74%) parents/caregivers, and 90% reported behavior changes to reduce TSE. There
was a 13% reported quit rate among the 99 parents/caregivers who smoked (95%
confidence interval: 7-21). Other behavior changes reported included initiating
home and vehicle smoking bans, discussing reduction of the child's smoke
exposure, and showing the video to others. Improvement in knowledge after this
brief intervention was associated with reported initiation of home and vehicle
smoking bans (P < .01). CONCLUSIONS: Parents and caregivers of smoke-exposed
children hospitalized for respiratory illnesses had high baseline knowledge of
the effects of TSE. A brief intervention that included a motivational video was
associated with reported behavior changes in parents/caretakers that decreased
second- and third-hand smoke. Improvement of knowledge was associated with
institution of home and vehicle smoking bans.
PMID- 26427923
TI - Triage of Intermediate-Care Patients in Pediatric Hospitals.
AB - BACKGROUND: Hospitalized children have a wide range of acuity and risk of
decompensation. The objective of this study was to determine where pediatric
patients are triaged when they present to pediatric hospitals needing intense
monitoring and nursing care, but do not require invasive monitoring or
technology. METHODS: We completed a telephone survey of pediatric hospitals in
the United States with at least 2 non-neonatal pediatric wards and at least 50
acute inpatient beds. The survey consisted of a brief scripted portrayal of 6
hypothetical patients who may be admitted to a hospital's general floor, ICU, or
an intermediate care unit (IMCU). The scenarios included severe asthma,
bronchiolitis, croup, diabetic ketoacidosis, and patients dependent on home
ventilation via noninvasive interface or tracheostomy. The hospital bed
coordinator or emergency department charge nurse was asked where each
hypothetical patient would be admitted in their hospital. RESULTS: A total192
hospitals met inclusion criteria and 164 hospitals (85%) responded. For all of
the scenarios, most of the institutions triaged them to the PICU. Twenty-eight
(17%) of the responding institutions triaged at least 1 of the patient scenarios
to an IMCU. The presence of an IMCU decreased triage to the ICU for all scenarios
when comparing hospitals with and without an IMCU (P < .001). CONCLUSIONS:
Inpatient triage practices among pediatric hospitals vary widely for patients who
require intense nursing or frequent monitoring due to specific acute illnesses or
respiratory technologies. Institutions that have an IMCU available are less
likely to send these patients to the ICU.
PMID- 26427924
TI - Pediatric Post-Acute Hospital Care: Striving for Identity and Value.
AB - The landscape of hospital care for children is changing. Hospital clinicians are
challenged to provide high-quality care to 2 increasingly complex groups of
children: (1) healthy children admitted for high-severity acute illnesses or
injury and (2) children admitted with lifelong, and often disabling, chronic
conditions. Hospitalizations for both of these groups are becoming more
prevalent, lengthy, and costly. In many situations, these children need weeks, or
sometimes months, to recover from their illness or injury, with a sustained
intensity of daily caregiving needs throughout their recovery period. Pediatric
post-acute hospital care is a little-known and underused option in pediatric
health care that could substantially help these children stabilize in a less
restrictive and less costly environment than acute care hospitals can provide. In
this commentary, we (1) propose the need and place for pediatric post-acute care
hospitals along the continuum of care, (2) discuss the characteristics of
children currently cared for in pediatric post-acute care hospitals, (3) suggest
research opportunities and challenges, and (4) present issues related to the cost
and value of pediatric post-acute care hospitals.
PMID- 26427925
TI - Taking Chances With Strep Throat.
PMID- 26427926
TI - Crawling Toward a Diagnosis: Vesicles and Thrombocytopenia in a Neonate.
PMID- 26427927
TI - Interferon-beta promotes macrophage foam cell formation by altering both
cholesterol influx and efflux mechanisms.
AB - Foam cell formation is a crucial event in atherogenesis. While interferon-beta
(IFNbeta) is known to promote atherosclerosis in mice, studies on the role of
IFNbeta on foam cell formation are minimal and conflicting. We therefore extended
these studies using both in vitro and in vivo approaches and examined IFNbeta's
function in macrophage foam cell formation. To do so, murine bone marrow-derived
macrophages (BMDMs) and human monocyte-derived macrophages were loaded with acLDL
overnight, followed by 6h IFNbeta co-treatment. This increased lipid content as
measured by Oil red O staining. We next analyzed the lipid uptake pathways of
IFNbeta-stimulated BMDMs and observed increased endocytosis of DiI-acLDL as
compared to controls. These effects were mediated via SR-A, as its gene
expression was increased and inhibition of SR-A with Poly(I) blocked the IFNbeta
induced increase in Oil red O staining and DiI-acLDL endocytosis. The IFNbeta
induced increase in lipid content was also associated with decreased ApoA1
mediated cholesterol efflux, in response to decreased ABCA1 protein and gene
expression. To validate our findings in vivo, LDLR(-/-) mice were put on chow or
a high cholesterol diet for 10weeks. 24 and 8h before sacrifice mice were
injected with IFNbeta or PBS, after which thioglycollate-elicited peritoneal
macrophages were collected and analyzed. In accordance with the in vitro data,
IFNbeta increased lipid accumulation. In conclusion, our experimental data
support the pro-atherogenic role of IFNbeta, as we show that IFNbeta promotes
macrophage foam cell formation by increasing SR-A-mediated cholesterol influx and
decreasing ABCA1-mediated efflux mechanisms.
PMID- 26427928
TI - Pharmacophore and QSAR Modeling of Neuronal Nitric Oxide Synthase Ligands and
Subsequent Validation and In Silico Search for New Scaffolds.
AB - Neuronal Nitric Oxide synthase (nNOS) is an attractive challenging target for the
treatment of various neurodegenerative disorders. To date, several structure
based studies were conducted to search novel selective nNOS inhibitors.
OBJECTIVE: Discovery of novel nNOS lead scaffolds through the integration of
ligand-based threedimensional (3D) pharmacophore (s) with quantitative structure
activity relationship model. METHOD: The pharmacophoric space of ten structurally
diverse sets acquired from 145 previously reported nNOS inhibitors was scrutinize
to fabricate representative pharmacophores. Afterwards, genetic algorithm
together with multiple linear regression analysis was applied to find out an
optimal pharmacophoric models and 2D physicochemical descriptors able to produce
optimal predictive QSAR equation (r(2) 116 =0.76, F = 353, r(2) LOO = 0.69, r(2)
PRESS against 29 external test ligands =0.51). A minimum of three binding modes
between ligands and nNOS binding pocket rationalized by the emergence of three
pharmacophoric models in the QSAR equation were illustrated. The QSAR-selected
pharmacophores were validated by receiver operating characteristic curves
analysis and afterward invested as a tool for screening national cancer institute
(NCI) database. RESULTS: Low micro molar novel nNOS inhibitors were revealed.
CONCLUSION: Two structurally diverse compounds 148 and 153 demonstrated new
scaffolds toward the discovery of potent nNOS inhibitors.
PMID- 26427929
TI - New Antimycobacterial Leads from Multicomponent Hydrazino-Ugi Reaction.
AB - BACKGROUND: Previously, modification of isoniazide- and pyrazinamide-derived
pharmacophores via the Ugi multicomponent reaction proved to be an effective
strategy to obtain efficacious and non-cytotoxic antimycobacterial leads.
OBJECTIVE: To apply the hydrazino-Ugi reaction developed in our group toward
modifying these pharmacophores with similar appendages as reported previously; to
create hydrolytically more stable compounds which are based on acyl hydrazine,
rather than diamide backbone. METHOD: Six hydrazino-Ugi products were synthesized
and modified at the reactive nitrogen atom via reductive alkylation.
Additionally, by conducting the hydrazino-Ugi reaction in methanol, three methyl
ester by-products were obtained and tested alongside the main library. Compounds
were screened against M. tuberculosis H37Rv strain and checked for cytotoxicity
vs. HEK293 cells. Hydrolytic stability of a model Ugi and one of the newly
synthesized hydrazino-Ugi products was compared in rat plasma stability
experiments. RESULTS: 6 out of 20 compounds prepared and tested, displayed potent
inhibition of M. tuberculosis growth and virtually no cytotoxicity in the testing
concentration range. The stability of a sample hydrazino-Ugi product in rat
plasma was over 3 times higher compared to that of one of the Ugi products
reported earlier. CONCLUSION: Hydrazino-Ugi reaction represents an effective way
to modify classical antitubercular chemotypes and generate compounds endowed with
specific antimycobacterial activity. These are new, hydrolytically stable leads
for the future antitubercular therapy development.
PMID- 26427930
TI - QSRR and QSAR Studies of Antitumor Drugs in View of their Biological Activity
Prediction.
AB - BACKGROUND: The QSRRs and QSARs are relatively new approaches to relate internal
chemical structure and particular biological activity. This methodology is based
on theory that mechanisms which took place into chromatography column are similar
to those that occur in a living organism at the molecular level, for example when
compounds penetrate into cells. OBJECTIVE: In this paper, we aim to describe
different cytostatic activities of selected anticancer drugs as QSRR and QSAR
models, and prove usefulness of connected QSRR and QSAR methodology in different
types of studies. METHOD: Chromatographic experiments using gradient RP-HPLC
method and different C18 stationary phases were performed. As a result we
obtained retention parameter log kw. Moreover, to calculate descriptors, which
characterize lipophilicity of analyzed antitumor drugs, DryLab program was
utilized. Molecular modeling studies were performed by using HyperChem program.
Dragon software was used to calculate structural descriptors, and then selected
descriptors were used to build QSRR and QSAR models. Obtained data were analyzed
by multiple regression analysis (MLR). RESULTS: Experimental log kw and predicted
log kw from QSRR models developed, were further used in QSAR analysis. The
goodness of fit was in the range of R2= 0.75 - 0.95, and the predictive
performance of the models was Q2 = 0.6 - 0.81. CONCLUSION: Both QSRR and QSAR
strategies presented in this paper, allowed predicting HPLC retention parameters
and cytotoxic activities of anticancer medicines without the necessity to carry
out time-consuming and expensive experimental tests.
PMID- 26427931
TI - Monooxime Bispyridinium Reactivators Bearing Xylene Linker Synthesis and In Vitro
Evaluation on Model of Organophosphate-Inhibited Acetylcholinesterase.
AB - Nine novel mono-oxime reactivators bearing xylene linker were synthesized in an
effort to improve previously prepared xylene bisoximes and monocarbamoyl
monooximes. The novel compounds were tested in vitro on the model of tabun-,
paraoxon-, methylparaoxon- and DFP-inhibited human erythrocyte AChE. Their
reactivation ability was compared to pralidoxime, asoxime, obidoxime and two
previously prepared xylene linked bisoximes (K107, K108). All compounds showed
minimal reactivation of tabun-inhibited AChE at selected concentration scale.
This finding was explained by molecular modelling study. Bisoximes obidoxime and
K108 resulted as the best reactivators for paraoxon-, methylparaoxon- and DFP
inhibited AChE. The loss of nonoxime moiety lead to the loss of reactivation
ability within the novel compounds. Though the novel reactivators did not exceed
previously known compounds, they confirmed former SAR findings for xylene-linked
AChE reactivators.
PMID- 26427932
TI - A public mental health approach in humanitarian settings is worthy of
consideration, with evidence.
PMID- 26427933
TI - Catalytic potential of highly defective (211) surfaces of zinc blende ZnO.
AB - Zinc blende (ZB) ZnO has gained increasing research interest due to its favorable
properties and its stabilization on the nanoscale. While surface properties are
important on the nanoscale, the studies on ZB ZnO surface properties are rare.
Here we have performed first principles calculations of the energies and
structures of ZB and wurtzite (WZ) ZnO surfaces. Our results indicate that, among
the four surfaces parallel to the polar axes, such as (1010) and (1120) of the WZ
phase and (110) and (211) of the ZB phase, the polar (211) surface has
substantially lower surface vacancy formation energies than the others, which
makes ZB ZnO promising for catalytic applications. Our results also imply that
the stabilization of ZB ZnO on the nanoscale is due to some mechanisms other than
surface energies.
PMID- 26427934
TI - Hospital food waste and environmental and economic indicators--A Portuguese case
study.
AB - This study presents a comprehensive characterization of plate waste (food served
but not eaten) at an acute care hospital in Portugal and elaborates on possible
waste reduction measures. Even though waste prevention is a priority in Europe,
large amounts of food are still being wasted every day, with hospitals giving
rise to two to three times more food waste than other foodservice sectors. For
this work the plate waste arising at the ward level was audited during 8 weeks,
covering almost 8000 meals, using a general hospital as case study. Weighing the
food served to patients and that returned after the meal allowed calculating
plate waste for the average meal, as well as for individual meal items.
Comparison of food waste arising showed that differences exist among wards, with
some generating more waste than others. On average each patient throws away 953 g
of food each day, representing 35% of the food served. This equates to 8.7
thousand tonnes of food waste being thrown away each year at hospitals across
Portugal. These tonnes of food transformed into waste represent economic losses
and environmental impacts, being estimated that 16.4 thousand tonnes of CO2
(equivalent) and 35.3 million euros are the annual national indicators in
Portugal. This means that 0.5% of the Portuguese National Health budget gets
thrown away as food waste. Given the magnitude of the food problem five measures
were suggested to reduce food waste, and their potential impact and ease of
implementation were discussed. Even though food waste is unavoidable the results
obtained in this work highlight the potential financial and environmental savings
for Portuguese hospitals, providing a basis to establish future strategies to
tackle food waste.
PMID- 26427935
TI - Mesophilic and thermophilic anaerobic digestion of the liquid fraction of pressed
biowaste for high energy yields recovery.
AB - Deep separate collection of the organic fraction of municipal solid waste
generates streams with relatively low content of inert material and high
biodegradability. This material can be conveniently treated to recovery both
energy and material by means of simplified technologies like screw-press and
extruder: in this study, the liquid fraction generated from pressed biowaste from
kerbside and door-to-door collection was anaerobically digested in both
mesophilic and thermophilic conditions while for the solid fraction composting is
suggested. Continuous operation results obtained both in mesophilic and
thermophilic conditions indicated that the anaerobic digestion of pressed
biowaste was viable at all operating conditions tested, with the greatest
specific gas production of 0.92m(3)/kgVSfed at an organic loading rate of
4.7kgVS/m(3)d in thermophilic conditions. Based on calculations the authors found
that the expected energy recovery is highly positive. The contents of heavy
metals and pathogens of fed substrate and effluent digestates were analyzed, and
results showed low levels (below End-of-Waste 2014 criteria limits) for both the
parameters thus indicating the good quality of digestate and its possible use for
agronomic purposes. Therefore, both energy and material were effectively
recovered.
PMID- 26427936
TI - Evaluation of different end-of-life management alternatives for used natural cork
stoppers through life cycle assessment.
AB - An important aspect of sustainable development is the implementation of effective
and sustainable waste management strategies. The present study focuses on a Life
Cycle Assessment (LCA) approach to different waste management strategies for
natural cork stoppers, namely incineration at a municipal solid waste
incinerator, landfilling in a sanitary landfill, and recycling. In the
literature, there are no LCA studies analyzing in detail the end-of-life stage of
natural cork stoppers as well as other cork products. In addition, cork is
usually treated as wood at the end-of-life stage. Thus, the outcome of this study
can provide an important insight into this matter. The results showed that
different management alternatives, namely incineration and recycling, could be
chosen depending on the impact category considered. The former alternative
presented the best environmental results in the impact categories of climate
change, ozone depletion and acidification, while the latter for photochemical
ozone formation and mineral and fossil resource depletion. The landfilling
alternative did not present the best environmental performance in any of the
impact categories. However, when the biogenic carbon dioxide emission was
assessed for the climate change category, the landfilling alternative was found
to be the most effective since most of the biogenic carbon would be permanently
stored in the cork products and not emitted into the atmosphere. A sensitivity
analysis was performed and the results showed that there are various parameters
that can significantly influence the results (e.g., carbon content in cork and
decay rate of cork in the landfill). Thus, LCA studies should include a detailed
description concerning their assumptions when the end-of-life stage is included
in the boundaries since they can influence the results, and furthermore, to
facilitate the comparison of different end-of-life scenarios. The present study
and the obtained results could be useful for the decision-making process
concerning public solid waste policies and industrial strategies.
PMID- 26427938
TI - Early Results of Medicare's Bundled Payment Initiative for a 90-Day Total Joint
Arthroplasty Episode of Care.
AB - BACKGROUND: In 2011 Medicare initiated a Bundled Payment for Care Improvement
(BPCI) program with the goal of introducing a payment model that would "lead to
higher quality, more coordinated care at a lower cost to Medicare." METHODS: A
Model 2 bundled payment initiative for Total Joint Replacement (TJR) was
implemented at a large, tertiary, urban academic medical center. The episode of
care includes all costs through 90 days following discharge. After one year, data
on 721 Medicare primary TJR patients were available for analysis. RESULTS:
Average length of stay (LOS) was decreased from 4.27 days to 3.58 days (Median
LOS 3 days). Discharges to inpatient facilities decreased from 71% to 44%.
Readmissions occurred in 80 patients (11%), which is slightly lower than before
implementation. The hospital has seen cost reduction in the inpatient component
over baseline. CONCLUSION: Early results from the implementation of a Medicare
BPCI Model 2 primary TJR program at this medical center demonstrate cost-savings.
LEVEL OF EVIDENCE: IV economic and decision analyses-developing an economic or
decision model.
PMID- 26427937
TI - Examining influential factors in providers' chronic pain treatment decisions: a
comparison of physicians and medical students.
AB - BACKGROUND: Chronic pain treatment guidelines are unclear and conflicting, which
contributes to inconsistent pain care. In order to improve pain care, it is
important to understand the various factors that providers rely on to make
treatment decisions. The purpose of this study was to examine factors that
reportedly influence providers' chronic pain treatment decisions. A secondary aim
was to examine differences across participant training level. METHODS: Eighty
five participants (35 medical students, 50 physicians) made treatment decisions
for 16 computer-simulated patients with chronic pain. Participants then selected
from provided lists the information they used and the information they would have
used (had it been available) to make their chronic pain treatment decisions for
the patient vignettes. RESULTS: Frequency analyses indicated that most
participants reported using patients' pain histories (97.6 %) and pain
description (95.3 %) when making treatment decisions, and they would have used
information about patients' previous treatments (97.6 %) and average and current
pain ratings (96.5 %) had this information been available. Compared to
physicians, medical students endorsed more frequently that they would have used
patients' employment and/or disability status (p < 0.05). A greater proportion of
medical students wanted information on patients' use of illicit drugs and alcohol
to make treatment decisions; while a greater proportion of physicians reported
using personal experience to inform their decisions. DISCUSSION: This study found
providers use patients' information and their own experiences and intuition to
make chronic pain treatment decisions. Also, participants of different training
levels report using different patient and personal factors to guide their
treatment decisions. CONCLUSIONS: These results highlight the complexity of
chronic pain care and suggest a need for more chronic pain education aimed at
medical students and practicing providers.
PMID- 26427939
TI - Tibial Crest Osteotomy in Extensile Knee Exposure-A Modified, Low-Energy, Suture
Technique.
AB - BACKGROUND: Tibial crest osteotomy is an established extensile knee approach.
Complications include mal-union, non-union, and fixation problems.We have
designed a technique aimed at reducing complications through the principles of
low-energy osteotomy and suture repair. METHODS: We reviewed our clinical and
radiological results in 159 consecutive patients 181 osteotomies with a mean age
of 66 years, and an average follow up of 22 months. RESULTS: Union occurred in
all osteotomies (100%) at a mean period of 11 weeks. Proximal migration averaging
11.5 mm occurred in 6 osteotomies (3%). Crest fragmentation occurred in 11
osteotomies (6%), with all cases resulting in uncomplicated union. No extensor
mechanism failure or complications related to the suture material occurred.
CONCLUSION: We conclude that this technique results in satisfactory outcomes
whilst avoiding hardware-related problems.
PMID- 26427940
TI - Hip Resurfacing Implant Orientation Analysis: A Comparison of a Computer-Added
Design Technique and Computed Tomography.
AB - BACKGROUND: Accurate acetabular component orientation in hip resurfacing is
mandatory. The aim of this study is to analyze if interpretation of pelvic
radiographs with computer-added design (CAD) software is comparable to computed
tomography (CT) in measurement of acetabular anteversion and inclination of a
Birmingham Hip Resurfacing (BHR) hip. METHODS: A consecutive series of 49
patients (50 hips) who underwent hip resurfacing arthroplasty between 2005 and
2007 with the BHR system were retrospectively included. The surgical procedure
was performed by 1 orthopedic surgeon in the beginning of his learning curve.
Computer-added design software was used to measure acetabular component
orientation on an anteroposterior pelvic radiograph. These measurements were
compared with CT measurements. We calculated the correlation between the CAD
software and CT analysis. The degree of underestimation or overestimation was
determined, and a Bland-Altman plot was created to visualize the agreement
between CAD software and CT results. RESULTS: We analyzed 50 BHR hips with mean
inclination of 54.6 degrees and 55.6 degrees and mean anteversion of 24.8
degrees and 13.3 degrees measured by CT and CAD, respectively. Pearson
correlation coefficient for inclination was 0.69 (P < .001) and for anteversion
0.81 (P < .001). Computer-added design showed a mean underestimated anteversion
of 11.6 degrees (P < .001). There was no significant underestimation or
overestimation of inclination with CAD analysis compared to CT measurements.
CONCLUSION: The CAD software is useful to assess acetabular inclination in hip
resurfacing but underestimates anteversion.
PMID- 26427941
TI - Hypoalbuminemia Independently Predicts Surgical Site Infection, Pneumonia, Length
of Stay, and Readmission After Total Joint Arthroplasty.
AB - This study investigates the association between preoperative hypoalbuminemia, a
marker for malnutrition, and complications during the 30 days after total joint
arthroplasty. Patients who underwent elective primary total hip and knee
arthroplasty as part of the American College of Surgeons National Surgical
Quality Improvement Program were identified. Outcomes were compared between
patients with and without hypoalbuminemia (serum albumin concentration <3.5 g/dL)
with adjustment for patient and procedural factors. A total of 49603 patients
were included. In comparison to patients with normal albumin concentration,
patients with hypoalbuminemia had a higher risk for surgical site infection,
pneumonia, extended length of stay, and readmission. Future efforts should
investigate methods of correcting nutritional deficiencies prior to total joint
arthroplasty. If successful, such efforts could lead to improvements in short
term outcomes for patients.
PMID- 26427942
TI - Safe sequencing depth to estimate the intra-host heterogeneity of viruses.
AB - Massively parallel sequencing allows efficient determination of genomic sequences
and intra-host polymorphisms for viruses. However, the sequencing depth that
guarantees safe interpretation of the observed data is unclear. We demonstrated
that 10-fold genome coverage may allow safe genome assembly, and 1000-fold
coverage is required to obtain reliable polymorphism estimation.
PMID- 26427943
TI - The contribution of case study design to supporting research on Clubhouse
psychosocial rehabilitation.
AB - BACKGROUND: Psychosocial Clubhouses provide recovery-focused psychosocial
rehabilitation to people with serious mental illness at over 300 sites in more
than 30 countries worldwide. To deliver the services involved, Clubhouses employ
a complex mix of theory, programs and relationships, with this complexity
presenting a number of challenges to those undertaking Clubhouse research. This
paper provides an overview of the usefulness of case study designs for Clubhouse
researchers; and suggests ways in which the evaluation of Clubhouse models can be
facilitated. RESULTS: The paper begins by providing a brief explanation of the
Clubhouse model of psychosocial rehabilitation, and the need for ongoing
evaluation of the services delivered. This explanation is followed by an
introduction to case study design, with consideration given to the way in which
case studies have been used in past Clubhouse research. It is posited that case
study design provides a methodological framework that supports the analysis of
either quantitative, qualitative or a mixture of both types of data to
investigate complex phenomena in their everyday contexts, and thereby support the
development of theory. As such, case study approaches to research are well suited
to the Clubhouse environment. The paper concludes with recommendations for future
Clubhouse researchers who choose to employ a case study design. CONCLUSIONS:
While the quality of case study research that explores Clubhouses has been
variable in the past, if applied in a diligent manner, case study design has a
valuable contribution to make in future Clubhouse research.
PMID- 26427945
TI - A Pale Baby With Blue Blood.
AB - A previously healthy 9-month-old boy presented to the emergency department with
sudden onset of pallor and reduced activity. A detailed history and initial blood
tests revealed the diagnosis of oxidant stress-induced hemolysis caused by
glucose-6-phosphate dehydrogenase deficiency. However, the child also had a
second diagnosis that was revealed with additional testing. This case is
described to illustrate the dual diagnosis and management guidelines for both
potentially serious conditions.
PMID- 26427944
TI - Emergency Department Visits for Gastroenteritis Before and After Rotavirus
Vaccine Implementation in 2006.
AB - OBJECTIVES: Gastroenteritis (GE) accounts for a significant number of emergency
department (ED) visits in children. Several studies since the introduction of a
new rotavirus vaccine in 2006 have found decreases in rotavirus illness. We
sought to determine in a large multicenter ED database whether there was also a
decrease in ED visits in young children for GE. METHODS: DESIGN: Retrospective
cohort of ED visits. SETTING: 28 EDs with annual visits between 22,000 and
82,000. POPULATION: Consecutive patients between January 1, 1996, and December
31, 2011. PROTOCOL: We identified GE visits using International Classification of
Diseases 9th revision (ICD-9) codes. For each year, less than 5 years, we
determined the average daily percent of total ED visits for GE. We calculated the
decreases from 2005 to 2011 in the average daily percent GE visits for each year
of life and their 95% confidence intervals. RESULTS: There were 7,740,823 total
visits in the database, and 811,317 (10.5%) are younger than 5 years. The annual
percent of GE visits rose for all years of life from 1999 to 2005 and then
decreased from 2005 to 2011. The decreases from 2005 to 2011 were greatest in the
earliest years of life ranging from 41% in the first year of life to 15% in the
fifth year of life. CONCLUSIONS: We found a decrease in average daily ED visits
for GE in each year of life for those younger than 5 years after the introduction
of the rotavirus vaccine. This was most pronounced during the earliest years of
life.
PMID- 26427946
TI - Epiploic Appendagitis: A Rare Cause of Acute Abdominal Pain in Children. Report
of a Case and Review of the Pediatric Literature.
AB - A 9-year-old boy presented with acute onset of abdominal pain and vomiting.
History, physical examination, and initial laboratory testing failed to provide a
diagnosis. A computed tomography scan revealed the rare finding of epiploic
appendagitis. We review the literature of this rare, but increasingly recognized,
condition that mimics appendicitis and needs to be considered in the child with
acute abdominal pain.
PMID- 26427947
TI - Acute Migraine Management in Children.
AB - Migraines are common, incapacitating, and often stress inducing for pediatric
patients and parents alike. According to the Agency for Healthcare Research and
Quality, more than 1 million Americans seek emergency care every year due to
migraines, with increasing frequency among adolescents. The disease can vary in
severity and character, often mimicking life-threatening conditions, requiring
prompt nuanced recognition by emergency personnel and implementation of an
effective treatment strategy. Development of emergency department guidelines for
the management of pediatric migraines should be based on up-to-date evidence
supporting safe, appropriate therapies for children.
PMID- 26427949
TI - ECGs in the ED.
PMID- 26427950
TI - Authors' Response to "Parental Cannabis Abuse and Accidental Intoxication in
Children: Prevention by Detecting Neglectful Situations and At-Risk Families".
PMID- 26427951
TI - The Use of Point-of-Care Ultrasound to Evaluate for Intestinal Foreign Bodies in
the Pediatric Emergency Department.
AB - We present the use of point-of-care ultrasound to evaluate two patients with
examinations concerning for appendicitis who were found to have multiple magnets
ingested and subsequent bowel perforations. These cases illustrate the
consequences of magnet ingestion as well as the application of point-of-care
ultrasound for the identification of intestinal foreign bodies in children.
PMID- 26427952
TI - Ultrasonographic assessment of fetal growth in miniature "Shiba" goats (Capra
hircus).
AB - The aim of the present study was to monitor fetal growth in relation to
gestational stage to generate formulae which could be used to estimate fetal age
in goats. Eight miniature Shiba goats (Capra hircus) were examined weekly by
transrectal and transabdominal ultrasound scanning during the gestation period
between Day 21 and 126 days of gestation. For accurate judgment, all fetometric
parameters were measured at least three times per one examination for each
animal. Quantification of the growth of the fetus allowed the development of a
number of predictors of fetal age. Low correlations were associated with
measurement of the chest diameter (R(2)=0.869), trunk diameter (R(2)=0.8969),
tibia length (R(2)=0.8662) and placentome diameter (R(2)=0.8999). Moderate
correlation was assessed by calculation of the length of six successive lumbar
vertebrae (R(2)=0.9296), femur length (R(2)=0.9278), heart axis length
(R(2)=0.9382 and 0.9589; for the longitudinal and transverse axis, respectively),
occipitonasal length (R(2)=0.9527), umbilical cord diameter (R(2)=0.9119) and
orbit diameter (R(2)=0.9239). A high correlation was estimated in investigating
the length of six successive thoracic vertebrae (R(2)=0.9674), braincase diameter
(R(2)=0.9831) and crown rump length (R(2)=0.9848). In conclusion, the
intrauterine fetal biometry estimation through ultrasound might be useful to
predict the accurate gestational age in miniature goats.
PMID- 26427953
TI - Health systems research for policy change: lessons from the implementation of
rapid assessment protocols for diabetes in low- and middle-income settings.
AB - BACKGROUND: As many challenges exist for access to diabetes care in developing
countries, the International Insulin Foundation developed a Rapid Assessment tool
and implemented this approach to identify barriers to care and propose concrete
recommendations for decision makers. The objective of this paper is to identify
the factors that contributed to informing and influencing policymakers with
regards to this work. METHODS: A documentary review comprised Stage 1. Stage 2
used an online questionnaire to gain insight from users of the Rapid Assessment
results. Based on Stages 1 and 2, Stage 3 comprised in-depth interviews with a
total of nine individuals (one individual each from the six participating
countries; two individuals from the World Health Organization; one "Global
Diabetes Advocate"). Interviews were analyzed based on a list of themes developed
from Stage 2. RESULTS: Stage 1 led to the identification of various types of
documents referring to the results. The online questionnaire had a response rate
of 33%. Respondents directly involved in the assessment had a "Good" or "Very
Good" appreciation of most aspects and scored these higher than those not
directly involved. From the interviews, formalized methods and close
collaboration between the international team and local partners were strengths.
Trust and a relationship with local partners were also seen as assets. All
stakeholders valued the results and the credibility of the data generated. Local
partners felt that more could have been done for dissemination. CONCLUSION: This
study shows the importance of specific results from the different assessments. In
addressing complex issues having external experts involved was seen as an
advantage. The uptake of results was due to the credibility of the research which
was influenced by a mix of the people involved, past assessments, trusted local
partners, and the use of the results by knowledge brokers, such as the World
Health Organization. Through these brokers, others gained ownership of the data.
The methods used and the fact that this data was grounded in a local context also
reinforced its value. Despite limitations, this study offers a unique perspective
where a similar research approach was taken in six countries.
PMID- 26427954
TI - Translational assessment of cardiac contractility by echocardiography in the
telemetered rat.
AB - INTRODUCTION: Cardiac contractility was evaluated using standard inotropic agents
in rats. We compared indices of cardiac contractility, i.e. LV dP/dt max from
telemetry while simultaneously collecting EF (ejection fraction) and FS
(fractional shortening) measures from echocardiography. METHODS: Male Wistar rats
were instrumented with telemetry devices for measurements of blood pressure and
left ventricular pressure. Milrinone (PDE III inhibitor) and verapamil (L-type
calcium channel blocker) at doses of 0, 3, 10, and 30 mg/kg were administered
orally using a 4 * 4 Latin square crossover study design. Telemetry data were
recorded at predose and continuously for 24h post-dose. Echocardiographic
evaluations were conducted once at predose and at 1 and 2h after milrinone or
verapamil administration, respectively. During the recording of echocardiograms,
telemetry data were collected simultaneously. Blood samples were also collected
to confirm plasma drug exposure. RESULTS: As expected, milrinone increased LV
dP/dt max, EF and FS while verapamil decreased LV dP/dt max, EF and FS. Linear
regression analysis showed a positive correlation between LV dP/dt max and EF or
FS (P<0.001) with both test agents. A change in LV dP/dt max of 1000 mmHg/s was
found to correspond with a change in EF and FS of 13 and 16%, respectively, in
the telemetered rat. DISCUSSION: The correlation between contractility indices
assessed by telemetry and echocardiographic methods in rat models has not
received much attention to date. Our results with two reference compounds
demonstrate that both methods are sensitive to alterations in contractility
induced by inotropic agents administered to rats. The high degree of correlation
between changes in LV dP/dt max and EF or FS in the rat enables a translational
element of clinical relevance following changes in contractility indices when
measured with telemetry devices in preclinical studies.
PMID- 26427955
TI - Incidence and serotype distribution of invasive group B streptococcal disease in
young infants: a multi-country observational study.
AB - BACKGROUND: Group B Streptococcus (GBS) is a leading cause of serious infection
in very young infants. Robust incidence data from many geographic regions,
including Latin America and Asia, are however lacking. METHODS: A multicenter,
hospital-based observational study was performed in Panama, Dominican Republic,
Hong Kong and Bangladesh. All represented urban, tertiary referral hospitals,
except Bangladesh. GBS cases (microbiological isolation from normally sterile
sites in infants aged 0-89 days) were collected over 12 months. RESULTS: At 2.35
(95% CI: 1.74-3.18) cases per 1000 live births, the incidence of early onset GBS
disease (EOD) was highest in the Dominican Republic, compared with 0.76 (95% CI:
0.41-1.39) in Hong Kong and 0.77 (95% CI: 0.44-1.35) in Panama, while no cases
were identified in Bangladesh. Over 90% of EOD cases occurred on the first day of
life, with case fatality ratios ranging from 6.7% to 40%, varying by center, age
of onset and clinical presentation. Overall, 90% of GBS (EOD and late onset
disease) was due to serotypes Ia, Ib and III. CONCLUSIONS: The incidence rate of
early onset GBS infection reported in Dominican Republic was not dissimilar from
that described in the United States prior to screening and intrapartum antibiotic
prophylaxis, while the incidence in Hong Kong was higher than previously reported
in the Asian region. The failure to identify GBS cases in Bangladesh highlights a
need to better understand the contribution of population, healthcare and
surveillance practice to variation in reported incidence. Overall, the identified
disease burden and serotype distribution support the need for effective
prevention methods in these populations, and the need for community based
surveillance studies in rural areas where access to healthcare may be
challenging.
PMID- 26427956
TI - Identification of chemical constituents of Zanthoxylum heitzii stem bark and
their insecticidal activity against the malaria mosquito Anopheles gambiae.
AB - BACKGROUND: Zanthoxylum heitzii bark extracts have insecticidal properties and
have been reported to be used against malaria in Western Africa. Previously, it
has been shown that a hexane extract of the bark is toxic to adult females of the
mosquito Anopheles gambiae, a malaria vector. As part of our project on the
control of malaria vectors using plant extracts, the phytochemistry of Z. heitzii
bark hexane extract has been investigated with the aim to identify the major
components with adulticidal and larvicidal effects on An. gambiae. METHODS: Z.
heitzii stem bark was extracted with hexane, and the extract was fractionated to
isolate major components from the bark, identified by NMR spectroscopy. Isolated
compounds were tested for toxicity towards adult female An. gambiae mosquitoes
and for larvicidal effects towards An. gambiae. RESULTS: The alkaloid
dihydronitidine, the sesquiterpenoid caryophyllene oxide, the amide pellitorine
and the lignan sesamin were identified as the major constituents in Z. heitzii
bark. Pellitorine was toxic to both adult insects (LD50 50 ng/mg insect) and
larvae (LD50 13 MUg/ml). None of the other compounds were toxic to adults, but
caryophyllene oxide and sesamin exhibited moderate larvicidal effects (LD50 > 150
MUg/ml). A mixture of the four compounds in the same ratio as in the hexane
extract showed higher toxicity (LD50 34 ng/mg insect) towards adult insects than
the pure compounds. CONCLUSION: The toxicity of Z. heitzii bark hexane extract to
An. gambiae is mostly due to pellitorine, although interactions between
pellitorine and other, inactive constituents may enhance the activity of the
extract.
PMID- 26427957
TI - High-tech image-guided therapy versus low-tech, simple, cheap gynecologic
brachytherapy.
PMID- 26427958
TI - The fiber-optic imaging and manipulation of neural activity during animal
behavior.
AB - Recent progress with optogenetic probes for imaging and manipulating neural
activity has further increased the relevance of fiber-optic systems for neural
circuitry research. Optical fibers, which bi-directionally transmit light between
separate sites (even at a distance of several meters), can be used for either
optical imaging or manipulating neural activity relevant to behavioral circuitry
mechanisms. The method's flexibility and the specifications of the light
structure are well suited for following the behavior of freely moving animals.
Furthermore, thin optical fibers allow researchers to monitor neural activity
from not only the cortical surface but also deep brain regions, including the
hippocampus and amygdala. Such regions are difficult to target with two-photon
microscopes. Optogenetic manipulation of neural activity with an optical fiber
has the advantage of being selective for both cell-types and projections as
compared to conventional electrophysiological brain tissue stimulation. It is
difficult to extract any data regarding changes in neural activity solely from a
fiber-optic manipulation device; however, the readout of data is made possible by
combining manipulation with electrophysiological recording, or the simultaneous
application of optical imaging and manipulation using a bundle-fiber. The present
review introduces recent progress in fiber-optic imaging and manipulation
methods, while also discussing fiber-optic system designs that are suitable for a
given experimental protocol.
PMID- 26427959
TI - Test-retest reliability of the Shape/Texture Identification testTM in people with
chronic stroke.
AB - OBJECTIVE: To evaluate the test-retest reliability of the Shape/Texture
Identification test (STI-testTM) in persons with chronic stroke. DESIGN: A test
retest design. SETTING: University hospital outpatient setting. PARTICIPANTS:
Forty-five persons (mean age 65 years) with mild to moderate impairments in the
arm and hand > 6 months post stroke. INTERVENTIONS: Not applicable. MAIN MEASURE:
The STI-testTM was used to assess active touch of the hand. It consists of two
subtests: identification of shapes and identification of textures, each in three
different sizes. Both hands were assessed twice, one week apart. The reliability
of the data was evaluated with weighted Kappa statistics and the Svensson rank
invariant method (percentage agreement, systematic and random disagreements).
RESULTS: The median total score of the STI-testTM was 5 points (min-max 0-6
points) for the more affected hand and 6 points (min-max 3-6 points) for the less
affected hand at both test occasions. The weighted Kappa coefficient was 0.94 for
the more affected hand and 0.55 for the less affected hand. The percentage
agreement for the more affected hand was 69% for the subtest shapes and 82% for
the subtest textures, and for the less affected hand 62% and 91%, respectively.
There were no systematic or random disagreements for any of the subtests.
CONCLUSION: The STI-testTM is reliable to assess active touch of the hand after
stroke.
PMID- 26427960
TI - Effects of Whole Body Vibration Exercise associated with Quadriceps Resistance
Exercise on functioning and quality of life in patients with knee osteoarthritis:
a randomized controlled trial.
AB - OBJECTIVE: To determine effects of Whole Body Vibration Exercise (WBVE)
associated with quadriceps resistance exercises (QRE) versus QRE only on pain,
physical function, biomarkers in serum and urine, activities of daily living
(ADL), and quality of life in patients with knee osteoarthitis (OA). DESIGN:
Randomized-controlled trial . SETTING: Rehabilitation medicine outpatient
department of West China Hospital, Chengdu, Sichuan, People's Republic of China.
SUBJECTS: Forty-nine patients were assigned to WBVE+QRE and 50 to QRE . MAIN
OUTCOME MEASURES: Primary outcomes included pain assessed with visual analogue
scale (VAS), Timed up & go test (TUG), 6-min walk distance test (6MWD), Western
Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary
outcomes comprised range of motion, muscular strength, serum COMP and urinary CTX
II, Lequesne Index (LI), and SF-36. All outcomes were analyzed with mixed effects
regression. RESULTS: Compared with QRE, WBVE+QRE showed significantly greater
improvement in VAS at 4weeks ( p=0.03), in VAS ( p<0.01), 6MWD ( p=0.01), WOMAC
pain ( p=0.01), and WOMAC physical function ( p=0.02) at 16 weeks, and in all
primary outcomes at 24 weeks (all p<0.01). CONCLUSION: Over a six months period,
WBVE in combination with QRE was superior to QRE in most outcomes.
PMID- 26427961
TI - Toward a model-based cognitive neuroscience of mind wandering.
AB - People often "mind wander" during everyday tasks, temporarily losing track of
time, place, or current task goals. In laboratory-based tasks, mind wandering is
often associated with performance decrements in behavioral variables and changes
in neural recordings. Such empirical associations provide descriptive accounts of
mind wandering - how it affects ongoing task performance - but fail to provide
true explanatory accounts - why it affects task performance. In this perspectives
paper, we consider mind wandering as a neural state or process that affects the
parameters of quantitative cognitive process models, which in turn affect
observed behavioral performance. Our approach thus uses cognitive process models
to bridge the explanatory divide between neural and behavioral data. We provide
an overview of two general frameworks for developing a model-based cognitive
neuroscience of mind wandering. The first approach uses neural data to segment
observed performance into a discrete mixture of latent task-related and task
unrelated states, and the second regresses single-trial measures of neural
activity onto structured trial-by-trial variation in the parameters of cognitive
process models. We discuss the relative merits of the two approaches, and the
research questions they can answer, and highlight that both approaches allow
neural data to provide additional constraint on the parameters of cognitive
models, which will lead to a more precise account of the effect of mind wandering
on brain and behavior. We conclude by summarizing prospects for mind wandering as
conceived within a model-based cognitive neuroscience framework, highlighting the
opportunities for its continued study and the benefits that arise from using well
developed quantitative techniques to study abstract theoretical constructs.
PMID- 26427962
TI - Repetition suppression in transcranial magnetic stimulation-induced motor-evoked
potentials is modulated by cortical inhibition.
AB - Transcranial magnetic stimulation (TMS) can be applied to modulate cortical
phenomena. The modulation effect is dependent on the applied stimulation
frequency. Repetition suppression (RS) has been demonstrated in the motor system
using TMS with short suprathreshold 1-Hz stimulation trains repeated at long
inter-train intervals. RS has been reported to occur in the resting motor-evoked
potentials (MEPs) with respect to the first pulse in a train of stimuli. Although
this RS in the motor system has been described in previous studies, the neuronal
origin of the phenomenon is still poorly understood. The present study evaluated
RS in three TMS-induced motor responses; resting and active MEPs as well as
corticospinal silent periods (SPs) in order to clarify the mechanism behind TMS
induced RS. We studied 10 healthy right-handed subjects using trains of four
stimuli with stimulation intensities of 120% of the resting motor threshold (rMT)
and 120% of the silent period threshold for an SP duration of 30 ms (SPT30).
Inter-trial interval was 20s, with a 1-s inter-stimulus interval within the
trains. We confirmed that RS appears in resting MEPs (p < 0.001), whereas active
MEPs did not exhibit RS (p > 0.792). SPs, on the contrary, lengthened (p < 0.001)
indicating modulation of cortical inhibition. The effects of the two stimulation
intensities exhibited a similar trend; however, the SPT30 evoked a more profound
inhibitory effect compared to that achieved by rMT. Moreover, the resting MEP
amplitudes and SP durations correlated (rho ? -0.674, p < 0.001) and the pre-TMS
EMG level did not differ between stimuli in resting MEPs (F = 0.0, p ? 0.999).
These results imply that the attenuation of response size seen in resting MEPs
might originate from increasing activity of inhibitory GABAergic interneurons
which relay the characteristics of SPs.
PMID- 26427964
TI - Talking about Death with Children with Incurable Cancer: Perspectives from
Parents.
AB - OBJECTIVE: To investigate the rationale and consequences associated with a
parent's decision to discuss death with a child with incurable cancer. STUDY
DESIGN: We present data from a larger retrospective study involving bereaved
parents of a child who died of cancer. Parents were asked whether they had
discussed the impending death with their child, whether they reflected on this
discussion positively, their reasons for not discussing death with their child,
and the manner in which the conversation regarding death occurred. The data were
analyzed qualitatively using a framework approach. RESULTS: Of the 86 parents of
56 children who answered the questions regarding discussing death with their
child, 55 parents of 35 children did not discuss the impending death with their
child. The following themes were identified: the parents' inability to discuss
the impending death; the parents' desire to protect their child; views regarding
talking with children; parents' views of child characteristics; the child's
unwillingness to discuss the subject; lack of opportunity to talk; and the
child's disability. The parents who did discuss death with their child generally
used symbolic and/or religious narratives, or they had brief, direct
conversations regarding death. The majority of parents felt positive regarding
their decision about whether to talk with their child about his/her impending
death. CONCLUSION: Most parents in this study cited several reasons for not
discussing death with their child. Our findings highlight the sensitive and
complex issues surrounding these conversations, indicating that there may be a
role for clinicians in supporting parents.
PMID- 26427963
TI - Relations among Adiposity and Insulin Resistance with Flow-Mediated Dilation,
Carotid Intima-Media Thickness, and Arterial Stiffness in Children.
AB - OBJECTIVE: To determine the associations of adiposity and insulin resistance with
measures of vascular structure and function in children. STUDY DESIGN: A cross
sectional study included 252 children (age 15.1 +/- 2.4 years; body mass index
percentile 68.2 +/- 26.5%; Tanner 2-5). Measurements of body fat percentage were
obtained with dual-energy X-ray absorptiometry and visceral adipose tissue (VAT)
with computed tomography. Insulin resistance was measured with hyperinsulinemic
euglycemic clamp. Vascular measurements for endothelial function (brachial artery
flow-mediated dilation [FMD]), vascular structure (carotid intima-media thickness
[cIMT]), vascular stiffness (carotid incremental elastic modulus), and pulse wave
velocity were analyzed by tertiles of adiposity and insulin resistance.
Additional analyses with ANCOVA and linear regression were adjusted for Tanner,
sex, race, and family relationship; FMD was also adjusted for baseline artery
diameter. RESULTS: FMD was positively associated with high adiposity (body mass
index, body fat percentage, and VAT) (P < .01 all). Insulin resistance was not
associated with FMD. cIMT was significantly, positively related to obesity, VAT,
and insulin resistance (P < .05 all). No differences in carotid incremental
elastic modulus and pulse wave velocity were observed in relation to adiposity or
insulin resistance. CONCLUSIONS: The findings suggest that adiposity is
associated with higher FMD, and insulin resistance and VAT are associated with
higher cIMT in children. Further research is needed to clarify the progression of
these relations.
PMID- 26427965
TI - Non-High-Density Lipoprotein Cholesterol in Children with Diabetes: Proposed
Treatment Recommendations Based on Glycemic Control, Body Mass Index, Age, Sex,
and Generally Accepted Cut Points.
AB - Percentile-based non-high-density lipoprotein cholesterol levels were analyzed by
glycemic control, weight, age, and sex of children with type 1 diabetes (n =
26,358). Ten percent of all children and 25% of overweight adolescent girls
require both immediate lipid-lowering medication and lifestyle changes to achieve
non-high-density lipoprotein cholesterol levels <120 mg/dL and cardiovascular
risk reduction.
PMID- 26427966
TI - Wimberger Sign in Congenital Syphilis.
PMID- 26427967
TI - Stability and complications of miniplates for mandibular reconstruction with a
fibular graft: outcomes for 544 patients.
AB - Fibular flaps are usually used for the reconstruction of the mandible, but the
use of plate systems, including miniplates and reconstruction plates, has
recently been debated. We have made a retrospective study of 544 consecutive
patients who had fibular grafts with miniplates used for fixation, and also made
retrospective measurements of orthopantomographs from 37 patients to assess the
stability of the miniplates used in the fibular flaps. When miniplates were used
with fibular flaps there were 10.3% (56/544) complications, of which 4.8%
(26/544) were loosening of the screws, 2.6% (14/544) fracture of the plate, 1.5%
(8/544) exposure of the plate, and 6.4% (35/544) infection. The median (IQR) time
at which the complications occurred was 24 (7-48) months. We conclude that
loosening of screws is common at the binding interface near the condyle and in
the molar region; plates are more likely to fracture near the binding interface
in proximity to the molar region; and plates at the chin are the most likely to
be exposed. Diabetes and the use of radiotherapy were associated with
complications. Our data suggest that miniplates used for mandibular
reconstruction are relatively reliable.
PMID- 26427968
TI - Evaluation of the efficacy and safety of propranolol, timolol maleate, and the
combination of the two, in the treatment of superficial infantile haemangiomas.
AB - Our aim was to compare in a prospective study the clinical effects and safety of
propranolol given orally, timolol maleate applied locally, and the combination of
the two, in the management of superficial infantile haemangiomas. Thirty-nine
patients with superficial infantile haemangiomas were randomised into three equal
groups of 13 each: the first given timolol maleate applied topically together
with propranolol given orally, the second given only propranolol orally, and the
third given only timolol maleate topically. Photographs were taken before, and
periodically after, starting treatment. A minimum of 50% improvement was
considered to be effective. The maximum duration of treatment was planned for 6
months, and the patients were followed up for 3-12 months. The overall rate of
clinical effectiveness for the three groups was 11/13, 9/13, and 8/13,
respectively. The two drugs together had a shorter effective response time than
when they were given separately. There were no serious adverse effects. We
therefore conclude that timolol maleate given topically together with propranolol
given orally is safe and effective in the treatment of superficial infantile
haemangiomas. Compared with simple medication, this method is more rapid, has an
appreciable effect, takes a shorter time, and has fewer adverse reactions. It
could be used as a first-line treatment, particularly if the lesion is
potentially disfiguring or functionally threatening such as large periocular
superficial haemangiomas.
PMID- 26427969
TI - Prevalence of biphasic response in anaphylaxis due to purposeful administration
of allergenic food.
PMID- 26427971
TI - Heart Failure and Low Health Literacy: Mitigating This Lethal Combination.
PMID- 26427972
TI - Safety First! Using a Checklist for Intrafacility Transport of Adult Intensive
Care Patients.
AB - BACKGROUND: Adult critical care patients in an academic medical center
experienced adverse events during intrafacility transport resulting from lack of
preparation. An intervention was needed to help keep patients safe during
intrafacility transport. OBJECTIVE: To develop a checklist for transport that is
easy to use and effective in preparing patients for transport. METHOD: A
checklist was developed and implemented. Elements of the checklist include
preparation of the patient before transport, screening of patients for criteria
that may place them at higher risk during transport, and a checklist for the
procedural site. RESULTS: From May 2011 through July 2014, 2506 transports were
conducted. Of these, 97.6% (n = 2445) involved no reported complications.
CONCLUSION: This tool is suitable for bedside clinicians to use when preparing
patients for transport.
PMID- 26427973
TI - Implementation of a Progressive Mobilization Program in a Medical-Surgical
Intensive Care Unit.
AB - BACKGROUND: Current literature supports implementation of progressive mobility
protocols in intensive care units. Education can help nurses overcome barriers to
mobility and increase knowledge about the positive effects of mobility.
OBJECTIVE: To evaluate the effect of education for a progressive mobilization
program for intensive care nurses on knowledge and performance. METHODS: A
pretest-posttest evaluation was conducted for 41 nurses, and a chart review was
performed before and after implementation of the educational intervention to
evaluate changes in knowledge and mobilization. RESULTS: Scores after the
educational intervention were significantly higher than scores before the
intervention (t = 2.02; P < .001). Overall mobilization (P = .04) and dangling (P
= .01) increased significantly after the education. No significant increases
occurred in ambulating or getting patients up to a chair. CONCLUSIONS:
Mobilization education was effective and increased nurses' knowledge about the
benefits of mobility for critically ill patients. The educational program also
affected how nurses performed mobility interventions. Although provision of
education had positive effects on patients' mobility, leadership and coaching are
still important components in implementing change.
PMID- 26427974
TI - Overcoming Barriers to Palliative Care Consultation.
AB - Palliative care consultations for patients with life-threatening illnesses
provide benefits for the patients and their families as well as for the health
care team. Patients have better quality of life and live longer but cost the
health care system less. Still, many patients are not offered the opportunity to
receive a palliative care consultation. Barriers to palliative care consultation
for patients in critical care units include misunderstandings about palliative
care and not having agreed upon criteria for referral. Critical care nurses can
assist in overcoming these barriers.
PMID- 26427975
TI - Prenatal Counseling and Care for Single-Ventricle Heart Disease: One Center's
Model for Care.
AB - Advances in prenatal imaging allow early detection of single-ventricle congenital
heart disease, which may enhance prenatal care and maximize care options and
decision making. Boston Children's Hospital's Advanced Fetal Care Center and
fetal cardiology program provide prenatal counseling and care for single
ventricle congenital heart disease. Key points for optimal prenatal counseling
and education include explanation of the diagnosis, delivery, the first surgery,
cardiac neurodevelopmental issues, feeding and growth issues, quality of life and
long-term care, family stressors, and fetal cardiac intervention. Such counseling
and education help families make the difficult decisions required in this
situation.
PMID- 26427976
TI - Critical Care in Critical Access Hospitals.
AB - What began as a grant-funded demonstration project, as a means of bridging the
gap in rural health care, has developed into a critical access hospital system
comprising 1328 facilities across 45 states. A critical access hospital is not
just a safety net for health care in a rural community. Such hospitals may also
provide specialized services such as same-day surgery, infusion therapy, and
intensive care. For hospitals located near the required minimum of 35 miles from
a tertiary care center, management of critically ill patients may be a matter of
stabilization and transfer. Critical access hospitals in more rural areas are
often much farther from tertiary care; some of these hospitals are situated
within frontier areas of the United States. This article describes the
development of critical access hospitals, provision of care and services,
challenges to critical care in critical access hospitals, and suggestions to
address gaps in research and collaborative care.
PMID- 26427977
TI - The Devil Is in the Details.
PMID- 26427978
TI - Use of Bicarbonate in Patients With Metabolic Acidosis.
PMID- 26427979
TI - Against All Odds: Preventing Pressure Ulcers in High-Risk Cardiac Surgery
Patients.
PMID- 26427981
TI - I Am a Critical Care Nurse.
PMID- 26427982
TI - Caring for Patients Treated With Therapeutic Hypothermia.
AB - Numerous studies have indicated that therapeutic hypothermia can improve
neurological outcomes after cardiac arrest. This treatment has redefined care
after resuscitation and offers an aggressive intervention that may mitigate
postresuscitation syndrome. Caregivers at Lehigh Valley Health Network,
Allentown, Pennsylvania, an academic, community Magnet hospital, treated more
than 200 patients with therapeutic hypothermia during an 8-year period. An
interprofessional team within the hospital developed, implemented, and refined a
clinical practice guideline for therapeutic hypothermia. In their experience,
beyond a protocol, 5 critical elements of success (interprofessional
stakeholders, coordination of care delivery, education, interprofessional case
analysis, and participation in a global database) enhanced translation into
clinical practice.
PMID- 26427983
TI - Tacrolimus use in lupus nephritis: A systematic review and meta-analysis.
AB - There is growing interest in the role of tacrolimus as a potential therapeutic
agent in SLE. This systematic review and meta-analysis evaluates the evidence for
tacrolimus use in the management of lupus nephritis. Thirteen controlled studies
were identified (9 suitable for inclusion), using Cochrane database, SCOPUS, Web
of Science and OVID (MEDLINE and EMBASE). Data on complete and partial remission
rates, proteinuria reduction and adverse events was extracted and analysed using
RevMan software. The meta-analysis showed that overall tacrolimus is more
effective at inducing complete renal remission than IVCYC (p=0.004), but there is
no significant difference compared to MMF (p=0.87). Multi-target TAC+MMF therapy
is more effective than IVCYC only when partial remission is included (p=0.0006).
Frequency of key adverse effects seems comparable to other agents used in the
management of lupus nephritis with fewer gastrointestinal side effects,
leukopenia, menstrual disorders, infections and episodes of liver dysfunction
reported, but more new onset hypertension and hyperglycaemia. Mortality was lower
in the tacrolimus groups, but this was not statistically significant (p=0.15).
Tacrolimus may be more effective at reducing proteinuria, but again this was not
statistically significant. There are no controlled trials looking at use in
pregnancy or juvenile patients, however case reports suggest potential efficacy
and safety. In conclusion, in moderately severe lupus nephritis, there is some
evidence supporting efficacy of tacrolimus or multi-target TAC+MMF over IVCYC,
but no evidence supporting tacrolimus over MMF. Tacrolimus may be more effective
at reducing proteinuria, having potential implications for long-term outcome. Key
limitations of this study are the lack of long-term outcome data and the lack of
high quality, large, blinded controlled trials in multi-ethnic groups.
PMID- 26427985
TI - New ideas for glaucoma.
PMID- 26427984
TI - Conservative treatment of retinoblastoma: a prospective phase II randomized trial
of neoadjuvant chemotherapy followed by local treatments and chemothermotherapy.
AB - PurposeIntraocular retinoblastoma treatments often combine chemotherapy and focal
treatments. A first prospective protocol of conservative treatments in our
institution showed the efficacy of the use of two courses of chemoreduction with
etoposide and carboplatin, followed by chemothermotherapy using carboplatin as a
single agent and diode laser. In order to decrease the possible long-term
toxicity of chemotherapy due to etoposide, a randomized neoadjuvant phase II
protocol was conducted using vincristine-carboplatin vs etoposide
carboplatin.Patients and methodsThe study was proposed when initial tumor
characteristics did not allow front-line local treatments. Patients included in
this phase II noncomparative randomized study of neoadjuvant chemotherapy
received vincristin-carboplatin (new arm) vs etoposide-carboplatin (our reference
arm). They were subsequently treated by local treatments and chemothermotherapy.
Primary end point was the need for secondary enucleation or external beam
radiotherapy (EBRT) not exceeding 40% at 2 years.ResultsA total of 65 eyes in 55
children were included in the study (May 2004 to August 2009). Of these, 32 eyes
(27 children) were treated in the arm etoposide-carboplatin and 33 eyes (28
children) in the arm vincristin-carboplatin. At 2 years after treatment, 23/33
(69.7%) eyes were treated and salvaged without EBRT or enucleation in the arm
vincristin-carboplatin and 26/32 (81.2%) in the arm etoposide
carboplatin.ConclusionEven if the two treatment arms could be considered as
sufficiently active according to the study decision rules, neoadjuvant
chemotherapy by two cycles of vincristine-carboplatin followed by
chemothermotherapy appear to offer less optimal local control than the etoposide
carboplatin combination.
PMID- 26427986
TI - Chloroquine retinopathy: pattern of presentation in Ibadan, Sub-Sahara Africa.
AB - BackgroundSelf-medication with chloroquine is common in Ibadan, Sub-Sahara
Africa. Retinopathy from chloroquine is not uncommon. The aim was to determine
the pattern of presentation.MethodologyCases of Chloroquine retinopathy seen at
the Retina and Vitreous Unit of the University College Hospital, Ibadan between
2008 and 2014 were reviewed. Information on age, sex, duration of chloroquine
use, and visual loss were retrieved. Visual acuity at presentation, anterior, and
posterior segment findings were documented. The results were analyzed using
proportions and percentages.ResultsFourteen cases were seen during the study
period. Mean age was 50.7 years. Male to female ratio was 3.5 : 1. Average
duration of visual loss before presentation was 2.7 years. Average duration of
self-medication with chloroquine was 5.3 years. Presenting visual acuity showed
2(14%) cases of bilateral blindness(VA<3/60 in both eyes); 5(35.7%) cases of
uniocular blindness; three cases of bilateral low vision(VA worse than 6/18 but
better than 3/60). Anterior segment examination showed abnormal sluggish
pupillary reaction in those with severe affectation. Dilated fundoscopy showed
features ranging from mild macular pigmentary changes and bulls eye maculopathy
to overt extensive retinal degeneration involving the posterior pole, attenuation
of retinal vessels, optic atrophy, and beaten bronze appearance of atrophic
maculopathy.ConclusionChloroquine retinopathy is not uncommon in Ibadan, Sub
Sahara Africa. Bulls eye maculopathy, extensive retinal, and macular degeneration
with optic atrophy are the main presentations. Public health education is
imperative.
PMID- 26427987
TI - Evaluation the adjunctive use of combined bevacizumab and mitomycinc to
trabeculectomy in management of recurrent pediatric glaucoma.
AB - PURPOSETO evaluate the efficacy and safety of combined bevacizumab-mitomycin c
(MMC) in recurrent cases of pediatric glaucoma.METHODSA prospective non-masked
controlled study that included bilateral cases of 12 patients (24 eyes) with
recurrent (had previous glaucoma surgery before) pediatric glaucoma. One eye in
each patient (12 eyes) was assigned to trabeculectomy operation with combined
application of MMC (0.4 mg/ml for 3 min) under and around the scleral flap before
trabeculectomy and bevacizumab (avastin) (2.5 mg in 0.2 ml) injected
subconjunctivally around the bleb after completing the surgery (group I). The
other eye of each patient (12 eyes) was assigned to trabeculectomy operation with
application of MMC (0.4 mg/ml for 3 min) only (group II). The mean follow-up
period was 13+/-1 months.ResultsThe mean age was 2.16+/-1.5 (range 7 months to
4.1 years). No significant difference in preoperative intraoperative pressure
(IOP) was observed between the groups (P>0.05). Recurrent primary congenital
glaucoma represents 66.7% of the cases. Other cases included were recurrent
aphakic and pseudophakic glaucoma 25% and recurrent post uveitic glaucoma 8.3%.
The mean IOP was 12.1+/-4.2, 12.6+/-5.4, and 12.8+/-5.2 mm Hg in group I at 3, 6,
and 12 months, respectively, and was 12.8+/-5.3, 13.7+/-6.7 and 15.6+/-5.9 mm Hg
in group II at 3, 6, and 12 months, respectively. There was a statistically
significant difference in the mean IOP between the studied groups at the 1-year
follow-up visit (P<0.05). In addition, group I showed a higher statistically
significant difference in absolute and total success (75 and 91.7%, respectively)
compared with group II (58.3 and 75%, respectively) (P<0.05). The encountered
complications included mild hyphema, which occurred in 8.33% in group 1, wound
leakage, which occurred in 8.33% in each group, and shallow anterior chamber
(AC), which occurred in 16.7% in each group and was the most common encountered
complication in the study. One case of shallow AC in group I led to choroidal
effusion (8.33%). One case in group II developed late bleb-related
endophthalmitis after 3 months, which resulted in phthisis bulbi
(8.33%).ConclusionThe additive effect of subconjunctival bevacizumab to MMC
augmented trabeculectomy in the case of recurrent pediatric glaucoma was
beneficial in improving the success rate. Better IOP control and prolonging the
bleb survivalvia reducing the long-term need of using anti-glaucoma drugs
postoperatively without adding complications had also been achieved with this
technique. This offers a promising alternative for the treatment of this type of
glaucoma.
PMID- 26427988
TI - Vision-related quality of life, metamorphopsia, and stereopsis after successful
surgery for rhegmatogenous retinal detachment.
AB - PurposeTo determine the relationship between vision-related quality of life,
metamorphopsia, and stereopsis after successful surgery to correct rhegmatogenous
retinal detachment (RRD).Patients and methodsData were obtained from 30 patients
with RRD who had scleral buckle surgery or vitrectomy. Age, gender, duration of
blurred vision, the best-corrected visual acuity (BCVA), extent of detachment,
and the location of retinal tears were measured before surgery. Approximately 1
year after surgery, stereopsis was measured with the Randot stereo test, visual
acuity (VA) was measured using a Snell VA acuity measurement at a distance of 5 m
and was presented as a linear LogMAR value, metamorphopsia was examined using an
M-chart, and vision-related quality of life was determined using the 25-Item
National Eye Institute Visual Function Questionnaire (VFQ-25).ResultsAll of the
patients achieved anatomical retinal reattachment. There was a significant
difference between preoperative BCVA (0.78+/-0.72) and BCVA 1 year
postoperatively (0.25+/-0.25) (P<0.05). Twenty-three patients had visual
distortion postoperatively, including vertical metamorphopsia (0.53+/-0.52
degrees ), and horizontal metamorphopsia (0.48+/-0.53 degrees ). Twenty patients
had no stereopsis. The composite score of VFQ-25 was 76.60 postoperatively.
Significant differences in postoperative BCVA, metamorphopsia, and VFQ-25 were
found between macula-on and macula-off groups (all P<0.05). There was a negative
correlation between VFQ-25 composite score and metamorphopsia (P<0.005); there
was no significant correlation between VFQ-25 composite score and BCVA or
stereopsis.ConclusionVision-related quality of life correlated with
metamorphopsia, but did not correlate with VA or stereopsis.
PMID- 26427989
TI - Clinical features of intratarsal keratinous cysts.
AB - PURPOSE: Intratarsal keratinous cysts (IKCs) have been frequently misdiagnosed as
chalazia or epidermal cysts. We reviewed a series of cases of IKCs to identify
clinical features that distinguish IKCs from other eyelid diseases. METHODS: We
retrospectively reviewed the medical records of 17 suspected IKC patients between
January 2004 and September 2014. RESULTS: Seventeen patients who were clinically
suspected to have IKC were enrolled. All patients presented with non-inflamed
eyelid nodules fixed to the tarsus. Among them, 12 biopsy specimens were
available and 11 patients (91.7%) were diagnosed with IKC, with a pathological
finding of stratified squamous cell lining with keratin material. The mean
patient age was 55.1 years (31-71). Six patients had a surgical history of
incision or incomplete excision of the lesion, followed by recurrence. On eyelid
eversion, five patients showed a white-yellow nodule, and three patients had a
bluish cystic lesion. The diameter of the nodules ranged from 4 to 10 mm. The
intracystic material was a milky white fluid. Ten patients underwent a complete
surgical excision including partial tarsectomy and there was no recurrence.
CONCLUSIONS: IKC can be distinguished from other intratarsal lesions by a
characteristic tarsal nodule fixed to the tarsus. To prevent recurrence, complete
excision with partial tarsectomy is needed.
PMID- 26427990
TI - Population diversity in Pacific herring of the Puget Sound, USA.
AB - Demographic, functional, or habitat diversity can confer stability on populations
via portfolio effects (PEs) that integrate across multiple ecological responses
and buffer against environmental impacts. The prevalence of these PEs in aquatic
organisms is as yet unknown, and can be difficult to quantify; however,
understanding mechanisms that stabilize populations in the face of environmental
change is a key concern in ecology. Here, we examine PEs in Pacific herring
(Clupea pallasii) in Puget Sound (USA) using a 40-year time series of biomass
data for 19 distinct spawning population units collected using two survey types.
Multivariate auto-regressive state-space models show independent dynamics among
spawning subpopulations, suggesting that variation in herring production is
partially driven by local effects at spawning grounds or during the earliest life
history stages. This independence at the subpopulation level confers a
stabilizing effect on the overall Puget Sound spawning stock, with herring being
as much as three times more stable in the face of environmental perturbation than
a single population unit of the same size. Herring populations within Puget Sound
are highly asynchronous but share a common negative growth rate and may be
influenced by the Pacific Decadal Oscillation. The biocomplexity in the herring
stock shown here demonstrates that preserving spatial and demographic diversity
can increase the stability of this herring population and its availability as a
resource for consumers.
PMID- 26427991
TI - Association between the FTOrs8050136 polymorphism and cancer risk: a meta
analysis.
AB - A meta-analysis on cancer risk relevant to FTOrs8050136 polymorphism. To
investigate the comprehensive effect of FTOrs8050136 polymorphism on cancer risk
based on a pooled result. Carcinogenesis is closely related to obesity. Both
obesity and cancer share common pathogenic factors such as hereditary
susceptibility and environmental predisposition. Recently, several studies had
reported that the FTOrs8050136 polymorphism, a genetic variation highly
associated with obesity, can be a potential cancer risk factor, while these
results were inconsistent. With the help of PubMed, EMBASE, Chinese National
Knowledge Infrastructure considerable research was done for potential studies
without language restriction. Pooled odds ratio combined with 95 % confidence
interval was employed to evaluate the potential correlations, and subgroup
analyses were performed based on the cancer types and ethnic populations. There
were eight articles comprising 21,810 cases and 85,070 controls met the
eligibility criteria. Overall, there was no significant association between the
FTOrs8050136 polymorphism and cancer risk (P = 0.163). Subgroup analysis
illustrated that no association existed between the FTOrs8050136 polymorphism and
cancer risk in Caucasians (P = 0.809), Asians (P = 0.412) and the mixed
population (P = 0.093). With regard to cancer types, the result suggested that
the FTOrs8050136 polymorphism had no connection with pancreatic cancer (P =
0.089), endometrial cancer (P = 0.353), prostate cancer (P = 0.578), colorectal
cancer (P = 0.054) and melanoma (P = 0.357), while the inverse result was
obtained in the subgroup of papillary thyroid cancer (P = 0.010). The
FTOrs8050136 polymorphism may be not associated with carcinogenesis apart from
papillary thyroid cancer, and further studies are needed to investigate the
potential correlation.
PMID- 26427992
TI - Computational and NMR Spectroscopic Evidence for Stereochemistry-Dependent
Conformations of 2,2,6,6-Tetramethylpiperidinyl-Masked 1,2-Diols.
AB - 2,2,6,6-Tetramethylpiperidinyl-masked 1,2-diols exhibited stereochemistry
dependent hydroxyl proton chemical shifts: ca. 7 ppm for the syn diastereomer and
ca. 2 ppm for the anti diastereomer. A computational search for low energy
geometries revealed that the syn isomer favors a six-membered ring hydrogen bond
to nitrogen and the anti isomer favors a five-membered ring hydrogen bond to
oxygen. The computed low energy conformations were found to have a large
difference in hydroxyl proton shielding that was reflected in the experimental
chemical shift difference. This chemical shift difference was observed in a broad
range of solvents, and thus may be useful as a stereochemical probe. The
stereochemistry-dependent conformation and chemical shift signature appeared to
be due to a syn pentane interaction between the gem-dimethyl groups on the
2,2,6,6-tetramethylpiperidinyl moiety.
PMID- 26427993
TI - No Evidence for Association of SCO2 Heterozygosity with High-Grade Myopia or
Other Diseases with Possible Mitochondrial Dysfunction.
AB - SCO2 mutations cause recessively inherited cytochrome c oxidase deficiency.
Recently Tran-Viet et al. proposed that heterozygosity for pathogenic SCO2
variants, including the common E140K variant, causes high-grade myopia. To
investigate the association of SCO2 mutations with myopia, ophthalmic
examinations were performed on 35 E140K carriers, one homozygous infant, and on a
mouse model of Sco2 deficiency. Additionally, a screen for other putative effects
of SCO2 heterozygosity was carried out by comparing the prevalence of the common
E140K variant in a population of patients with undiagnosed diseases compatible
with SCO2-related pathogenesis to that in a general population sample. High-grade
myopia was not identified in any of the studied individuals. Of the carriers, 17
were emmetropic, and 18 possessed refractive errors. Additionally, no significant
axial elongation indicative of high-grade myopia was found in mice carrying E129K
(corresponding to E140K in humans) knock-in mutations. The prevalence of E140K
carriers in the symptomatic cohort was evaluated as 1:103 (CI: 0.44-2.09) and did
not differ significantly from the population prevalence (1:147, CI: 0.45
1.04).Our study demonstrates that heterozygosity for pathogenic SCO2 variants is
not associated with high-grade myopia in either human patients or in mice.
PMID- 26427994
TI - Intracranial Pressure Monitoring Demonstrates that Cerebral Edema Is Not
Correlated to Hyperammonemia in a Child with Ornithine Transcarbamylase
Deficiency.
AB - BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) is an inborn error of
urea cycle resulting in increased plasma levels of ammonia and glutamine and
cerebral edema. However, the underlying mechanism of brain cytotoxicity remains
controversial. Our objective is to present an unusual acute hyperammonemic crisis
suggesting a key role of brain glutamine to mediate ammonia neurotoxicity and the
interest of intracerebral pressure (ICP) monitoring to maintain adequate cerebral
perfusion pressure and to prevent neurological damages. PATIENT: A 6-year-old boy
with OTCD was admitted for an acute hyperammonemic encephalopathy following viral
infection. At admission, he presented vomiting, confusion, lethargy (Glasgow
scale 7/15), and bilateral papilledema, suggesting cerebral edema. Plasma ammonia
level was slightly increased (194 MUmol/L, rr 25-50 MUmol/L), contrasting with
the severity of neurological deterioration and with high levels of glutamine in
plasma (1,949 MUmol/L, rr 335-666 MUmol/L) and the brain (10-fold increase on in
vivo MR spectroscopy). The patient was placed on neuroprotective treatments and
respiratory support. MAIN RESULTS: With a hypercaloric protein-free diet and
nitrogen scavenger drugs, plasma levels of ammonia and glutamine rapidly
decreased without neurological improvement. Continuous ICP monitoring showed
repetitive peaks of pressure up to 60 mmHg in the first four days and was helpful
to manage neuroprotective treatments. After several days, the patient
progressively recovered without cognitive or motor disability. CONCLUSION: This
case report highlights the discrepancy between the severity of neurological
impairment, presumably related to high level of brain glutamine, and plasma
levels of ammonia or glutamine in a child with acute hyperammonemic
encephalopathy related to OTCD. In this situation, continuous ICP monitoring was
helpful to manage neuroprotective treatments and prevent brain damages.
PMID- 26427995
TI - Developmental plasticity in vision and behavior may help guppies overcome
increased turbidity.
AB - Increasing turbidity in streams and rivers near human activity is cause for
environmental concern, as the ability of aquatic organisms to use visual
information declines. To investigate how some organisms might be able to
developmentally compensate for increasing turbidity, we reared guppies (Poecilia
reticulata) in either clear or turbid water. We assessed the effects of
developmental treatments on adult behavior and aspects of the visual system by
testing fish from both developmental treatments in turbid and clear water. We
found a strong interactive effect of rearing and assay conditions: fish reared in
clear water tended to decrease activity in turbid water, whereas fish reared in
turbid water tended to increase activity in turbid water. Guppies from all
treatments decreased activity when exposed to a predator. To measure plasticity
in the visual system, we quantified treatment differences in opsin gene
expression of individuals. We detected a shift from mid-wave-sensitive opsins to
long wave-sensitive opsins for guppies reared in turbid water. Since long
wavelength sensitivity is important in motion detection, this shift likely allows
guppies to salvage motion-detecting abilities when visual information is obscured
in turbid water. Our results demonstrate the importance of developmental
plasticity in responses of organisms to rapidly changing environments.
PMID- 26427996
TI - Differential protein expression analysis following olfactory learning in Apis
cerana.
AB - Studies of olfactory learning in honeybees have helped to elucidate the
neurobiological basis of learning and memory. In this study, protein expression
changes following olfactory learning in Apis cerana were investigated using
isobaric tags for relative and absolute quantification (iTRAQ) technology. A
total of 2406 proteins were identified from the trained and untrained groups.
Among these proteins, 147 were differentially expressed, with 87 up-regulated and
60 down-regulated in the trained group compared with the untrained group. These
results suggest that the differentially expressed proteins may be involved in the
regulation of olfactory learning and memory in A. cerana. The iTRAQ data can
provide information on the global protein expression patterns associated with
olfactory learning, which will facilitate our understanding of the molecular
mechanisms of learning and memory of honeybees.
PMID- 26427998
TI - Constraints and Benefits of Child Welfare Contracts with Behavioral Health
Providers: Conditions that Shape Service Access.
AB - This qualitative study examines worker perceptions of how public child welfare
agencies' purchase of service contracts with private behavioral health
organizations can both facilitate and constrain referral making and children's
access to services. Five, 90-min focus groups were conducted with workers (n =
50) from an urban public child welfare agency in the Midwest. Using a modified
grounded theory approach, findings suggest that contracts may expedite service
linkages, but contract benefits are conditioned upon design and implementation.
Results also suggest the critical role of front line workers in carrying out
contractual relationships. Implications for research and interventions for
enhancing contracting are discussed.
PMID- 26427997
TI - Role of serum hepatitis B virus marker quantitation to differentiate natural
history phases of HBV infection.
AB - PURPOSE: The purpose of this study was to characterize roles of serum hepatitis B
virus marker quantitation in differentiation of natural phases of HBV infection.
METHODS: A total of 184 chronic hepatitis B (CHB) patients were analyzed
retrospectively. Patients were classified into four categories: immune tolerant
phase (IT, n = 36), immune clearance phase (IC, n = 81), low-replicative phase
(LR, n = 31), and HBeAg-negative hepatitis phase (ENH, n = 36), based on
clinical, biochemical, serological, HBV DNA level and histological data. RESULTS:
Hepatitis B surface antigen (HBsAg) quantitation in four phases were 4.7 +/- 0.2,
3.8 +/- 0.5, 2.5 +/- 1.2 and 3.4 +/- 0.4 log10 IU/mL, respectively. There were
significant differences between IT and IC (p < 0.001) and between LR and ENH
phases (p < 0.001). Quantitation of hepatitis B e antigen (HBeAg) in IT and IC
phases are 1317.9 +/- 332.9 and 673.4 +/- 562.1 S/CO, respectively (p < 0.001).
Hepatitis B core antibody (HBcAb) quantitation in the four groups were 9.48 +/-
3.3, 11.7 +/- 2.8, 11.2 +/- 2.6 and 13.2 +/- 2.9 S/CO, respectively. Area under
receiver operating characteristic curve (AUCs) of HBsAg and HBeAg at cutoff
values of 4.41 log10 IU/mL and 1118.96 S/CO for differentiation of IT and IC
phases are 0.984 and 0.828, with sensitivity 94.4 and 85.2 %, specificity 98.7
and 75 %, respectively. AUCs of HBsAg and HBcAb at cutoff values of 3.4 log10
IU/mL and 10.5 S/CO for differentiation of LR and ENT phases are 0.796 and 0.705,
with sensitivity 58.1 and 85.7 %, and specificity 94.4 and 46.2 %, respectively.
CONCLUSIONS: HBsAg quantitation has high predictive value and HBeAg quantitation
has moderate predictive value for discriminating IT and IC phase. HBsAg and HBcAb
quantitations have moderate predictive values for differentiation of LR and ENH
phase.
PMID- 26427999
TI - What Factors are Associated with Consumer Initiation of Shared Decision Making in
Mental Health Visits?
AB - Understanding consumer initiation of shared decision making (SDM) is critical to
improving SDM in mental health consultations, particularly because providers do
not always invite consumer participation in treatment decisions. This study
examined the association between consumer initiation of nine elements of SDM as
measured by the SDM scale, and measures of consumer illness self-management and
the consumer-provider relationship. In 63 mental health visits, three SDM
elements were associated with self-management or relationship factors: discussion
of consumer goals, treatment alternatives, and pros and cons of a decision.
Limitations, implications, and future directions are discussed.
PMID- 26428000
TI - [Implementation of a rational standard of hygiene for preparation of operating
rooms].
AB - BACKGROUND: The assurance of high standards of care is a major requirement in
German hospitals while cost reduction and efficient use of resources are
mandatory. These requirements are particularly evident in the high-risk and cost
intensive operating theatre field with multiple process steps. The cleaning of
operating rooms (OR) between surgical procedures is of major relevance for
patient safety and requires time and human resources. The hygiene procedure plan
for OR cleaning between operations at the university hospital in Gottingen was
revised and optimized according to the plan-do-check-act principle due to not
clearly defined specifications of responsibilities, use of resources, prolonged
process times and increased staff engagement. METHODS: The current status was
evaluated in 2012 as part of the first step "plan". The subsequent step "do"
included an expert symposium with external consultants, interdisciplinary
consensus conferences with an actualization of the former hygiene procedure plan
and the implementation process. All staff members involved were integrated into
this management change process. The penetration rate of the training and
information measures as well as the acceptance and compliance with the new
hygiene procedure plan were reviewed within step "check". The rates of positive
swabs and air sampling as well as of postoperative wound infections were analyzed
for quality control and no evidence for a reduced effectiveness of the new
hygiene plan was found. After the successful implementation of these measures the
next improvement cycle ("act") was performed in 2014 which led to a
simplification of the hygiene plan by reduction of the number of defined cleaning
and disinfection programs for preparation of the OR. RESULTS: The reorganization
measures described led to a comprehensive commitment of the hygiene procedure
plan by distinct specifications for responsibilities, for the course of action
and for the use of resources. Furthermore, a simplification of the plan, a
rational staff assignment and reduced process times were accomplished. Finally,
potential conflicts due to an insufficient evidence-based knowledge of personnel
was reduced. CONCLUSION: This present project description can be used by other
hospitals as a guideline for similar changes in management processes.
PMID- 26428001
TI - Modulation of ALDH5A1 and SLC22A7 by microRNA hsa-miR-29a-3p in human liver
cells.
AB - Observed variations in drug responses among patients may result from differences
in heritable genetic traits or from alterations in the epigenetic regulation of
drug metabolizing enzymes and transporters (DMETs). MicroRNAs (miRNAs), a group
of small non-coding RNAs, provide an epigenetic mechanism for fine-tuning the
expression of targeted DMET genes by regulating the efficiency of protein
translation and by decreasing mRNA stability via enhanced degradation. In the
current study we systematically screened 374 important genes encoding DMETs for
potential response elements to hsa-miR-29a-3p, a highly abundant miRNA in human
liver. RNA electrophoresis mobility shift assays displayed direct interactions
between hsa-miR-29a-3p and its cognate targets within the mRNA transcripts for
the ABCC6, SLC22A7 and ALDH5A1 genes. The expression of luciferase reporter genes
containing the 3'-UTRs of SLC22A7 or ALDH5A1 and the expression of endogenous
SLC22A7 and ALDH5A1 were each suppressed by transfection with hsa-miR-29a-3p
mimics. Importantly, chemically-induced up-regulation of hsa-miR-29a-3p
correlated inversely with the expression of SLC22A7 and ALDH5A1. However, our
studies failed to detect suppressive effects of hsa-miR-29a-3p on ABCC6
expression, which might be explained by the notion that the interaction of hsa
miR-29a-3p and ABCC6 mRNA was unable to recruit ribonucleoproteins to form a RNA
induced silencing complex.
PMID- 26428002
TI - Thermodynamics and kinetics of inhibitor binding to human equilibrative
nucleoside transporter subtype-1.
AB - Many nucleoside transport inhibitors are in clinical use as anti-cancer,
vasodilator and cardioprotective drugs. However, little is known about the
binding energetics of these inhibitors to nucleoside transporters (NTs) due to
their low endogenous expression levels and difficulties in the biophysical
characterization of purified protein with ligands. Here, we present kinetics and
thermodynamic analyses of inhibitor binding to the human equilibrative nucleoside
transporter-1 (hENT1), also known as SLC29A1. Using a radioligand binding assay,
we obtained equilibrium binding and kinetic rate constants of well-known NT
inhibitors--[(3)H]nitrobenzylmercaptopurine ribonucleoside ([(3)H]NBMPR),
dilazep, and dipyridamole--and the native permeant, adenosine, to hENT1. We
observed that the equilibrium binding affinities for all inhibitors decreased
whereas, the kinetic rate constants increased with increasing temperature.
Furthermore, we found that binding is enthalpy driven and thus, an exothermic
reaction, implying that the transporter does not discriminate between its
inhibitors and substrates thermodynamically. This predominantly enthalpy-driven
binding by four chemically distinct ligands suggests that the transporter may not
tolerate diversity in the type of interactions that lead to high affinity
binding. Consistent with this, the measured activation energy of [(3)H]NBMPR
association was relatively large (20 kcal mol(-1)) suggesting a conformational
change upon inhibitor binding. For all three inhibitors the enthalpy (DeltaH
degrees ) and entropy (DeltaS degrees ) contributions to the reaction energetics
were determined by van't Hoff analysis to be roughly similar (25-75% DeltaG
degrees ). Gains in enthalpy with increasing polar surface area of inhibitors
suggest that the binding is favored by electrostatic or polar interactions
between the ligands and the transporter.
PMID- 26428003
TI - Mercury Distribution in the Deule River (Northern France) Measured by the
Diffusive Gradients in Thin Films Technique and Conventional Methods.
AB - The distribution of mercury in surface water and in sediment from Deule River in
Northern France was studied by application of conventional sampling methods and
by diffusive gradients in thin films technique (DGT). Concentration of total
dissolved mercury in surface water was 20.8 +/- 0.8 ng l(-1). The particulate
mercury concentration was 6.2 +/- 0.6 ug g(-1). The particulate mercury was
accumulated in sediment (9.9 +/- 2.3 mg kg(-1)), and it was transformed by
methylating bacteria to methylmercury, mainly in the first 2-cm layer of the
sediment. Total dissolved concentration of mercury in sediment pore water
obtained by application of centrifugation extraction was 17.6 +/- 4.1 ng l(-1),
and it was comparable with total dissolved pore water mercury concentration
measured by DGT probe containing Duolite GT-73 resin gel (18.2 +/- 4.3 ng l(-1)),
taking the sediment heterogeneity and different principles of the applied methods
into account. By application of two DGT probes with different resin gels specific
for mercury, it was found that approximately 30% of total dissolved mercury in
sediment pore water was present in labile forms easy available for biota. The
resolution of mercury DGT depth profiles was 0.5 cm, which allows, unlike
conventional techniques, to study the connection of the geochemical cycle of
mercury with geochemical cycles of iron and manganese.
PMID- 26428004
TI - Sources and Distribution of Trace Elements in Soils Near Coal-Related Industries.
AB - The degree of contamination of soil and the potential ecological risks associated
with five different coal-burning industries were assessed in Shanxi Province,
China. Results showed that the trace element concentrations in soil close to the
coal industries were higher than those in the background soils, and the
enrichment factors were >1. The potential ecological risk indexes ranged from 99
to 328 for the five coal-related industries. Results also illustrated that the
trace elements were transported through the atmosphere. Concentrations of B, Hg,
Mo, Pb, Se, Cr, Cu, Ni, V, Zn, and Mn were high in the area around the steel
plant. Principal component analysis and redundancy analysis indicated that the
sources of Se, Mo, Hg, Cd, As, Cr, B, Ni, and Cu were mainly anthropogenic,
whereas Pb, V, Cu, Zn, and Mn were from natural sources. The soil Hg and Se
contents were simulated by an artificial neural network model, which showed that
Hg and Se in soils were from atmospheric deposits and their spatial distributions
were related to the dominant wind direction. The potential ecological risk from
Hg was much higher (one order of magnitude) than that from the other trace
elements, which highlights the fact that it deserves urgent attention. Control of
emissions from the burning of coal and other raw materials (such as iron and
phosphate ores) should also be prioritized.
PMID- 26428005
TI - Towards an ICF core set for ADHD: a worldwide expert survey on ability and
disability.
AB - This is the second in a series of four empirical studies designed to develop
International Classification of Functioning, Disability and Health (ICF and
Children and Youth version, ICF-CY) core sets for attention deficit hyperactivity
disorder (ADHD). The objective of this stage was to gather the opinions from
international experts on which ability and disability concepts were considered
relevant to functioning in ADHD. An email-based survey was carried out amongst
international experts in ADHD. Relevant functional ability and disability
concepts were extracted from their responses and linked to the ICF/-CY categories
by two independent researchers using a standardised linking procedure. 174
experts from 11 different disciplines and 45 different countries completed the
survey. Meaningful concepts identified in their responses were linked to 185 ICF/
CY categories. Of these, 83 categories were identified by at least 5 % of the
experts and considered the most relevant to ADHD: 30 of these were related to
Body functions (most identified: attention functions, 85 %), 30 to Activities and
Participation (most identified: school education, 52 %), 20 to Environmental
factors (most identified: support from immediate family, 61 %), and 3 to Body
structures (most identified: structure of brain, 83 %). Experts also provided
their views on particular abilities related to ADHD, naming characteristics such
as high-energy levels, flexibility and resiliency. Gender differences in the
expression of ADHD identified by experts pertained mainly to females showing more
internalising (e.g. anxiety, low self-esteem) and less externalising behaviours
(e.g. hyperactivity), leading to a risk of late- and under-diagnosis in females.
Results indicate that the impact of ADHD extends beyond the core symptom domains,
into all areas of life and across the lifespan. The current study in combination
with three additional preparatory studies (comprehensive scoping review, focus
groups, clinical study) will provide the scientific basis to define the ADHD ICF/
CY core sets for multi-purpose use in basic and applied research and every day
clinical practice.
PMID- 26428007
TI - Maternal BCAS2 protects genomic integrity in mouse early embryonic development.
AB - Mammalian early embryos maintain accurate genome integrity for proper development
within a programmed timeline despite constant assaults on their DNA by
replication, DNA demethylation and genetic defects transmitted from germ cells.
However, how genome integrity is safeguarded during mammalian early embryonic
development remains unclear. BCAS2 (breast carcinoma amplified sequence 2), a
core component of the PRP19 complex involved in pre-mRNA splicing, plays an
important role in the DNA damage response through the RPA complex, a key
regulator in the maintenance of genome integrity. Currently, the physiological
role of BCAS2 in mammals is unknown. We now report that BCAS2 responds to
endogenous and exogenous DNA damage in mouse zygotes. Maternal depletion of BCAS2
compromises the DNA damage response in early embryos, leading to developmental
arrest at the two- to four-cell stage accompanied by the accumulation of damaged
DNA and micronuclei. Furthermore, BCAS2 mutants that are unable to bind RPA1 fail
in DNA repair during the zygotic stage. In addition, phosphorylated RPA2 cannot
localise to the DNA damage sites in mouse zygotes with disrupted maternal BCAS2.
These data suggest that BCAS2 might function through the RPA complex during DNA
repair in zygotes. Together, our results reveal that maternal BCAS2 maintains the
genome integrity of early embryos and is essential for female mouse fertility.
PMID- 26428006
TI - Osteogenic capillaries orchestrate growth plate-independent ossification of the
malleus.
AB - Endochondral ossification is a developmental process by which cartilage is
replaced by bone. Terminally differentiated hypertrophic chondrocytes are
calcified, vascularized, and removed by chondroclasts before bone matrix is laid
down by osteoblasts. In mammals, the malleus is one of three auditory ossicles
that transmit vibrations of the tympanic membrane to the inner ear. The malleus
is formed from a cartilaginous precursor without growth plate involvement, but
little is known about how bones of this type undergo endochondral ossification.
Here, we demonstrate that in the processus brevis of the malleus, clusters of
osteoblasts surrounding the capillary loop produce bone matrix, causing the
volume of the capillary lumen to decrease rapidly in post-weaning mice.
Synchrotron X-ray tomographic microscopy revealed a concentric, cylindrical
arrangement of osteocyte lacunae along capillaries, indicative of pericapillary
bone formation. Moreover, we report that overexpression of Fosl1, which encodes a
component of the AP-1 transcription factor complex, in osteoblasts significantly
blocked malleal capillary narrowing. These data suggest that
osteoblast/endothelial cell interactions control growth plate-free endochondral
ossification through 'osteogenic capillaries' in a Fosl1-regulated manner.
PMID- 26428009
TI - Intracellular lumen formation in Drosophila proceeds via a novel subcellular
compartment.
AB - Cellular tubes have diverse morphologies, including multicellular, unicellular
and subcellular architectures. Subcellular tubes are found prominently within the
vertebrate vasculature, the insect breathing system and the nematode excretory
apparatus, but how such tubes form is poorly understood. To characterize the
cellular mechanisms of subcellular tube formation, we have refined methods of
high pressure freezing/freeze substitution to prepare Drosophila larvae for
transmission electron microscopic (TEM) analysis. Using our methods, we have
found that subcellular tube formation may proceed through a previously
undescribed multimembrane intermediate composed of vesicles bound within a novel
subcellular compartment. We have also developed correlative light/TEM procedures
to identify labeled cells in TEM-fixed larval samples. Using this technique, we
have found that Vacuolar ATPase (V-ATPase) and the V-ATPase regulator
Rabconnectin-3 are required for subcellular tube formation, probably in a step
resolving the intermediate compartment into a mature lumen. In general, our
ultrastructural analysis methods could be useful for a wide range of cellular
investigations in Drosophila larvae.
PMID- 26428008
TI - Mechano-logical model of C. elegans germ line suggests feedback on the cell
cycle.
AB - The Caenorhabditis elegans germ line is an outstanding model system in which to
study the control of cell division and differentiation. Although many of the
molecules that regulate germ cell proliferation and fate decisions have been
identified, how these signals interact with cellular dynamics and physical forces
within the gonad remains poorly understood. We therefore developed a dynamic, 3D
in silico model of the C. elegans germ line, incorporating both the mechanical
interactions between cells and the decision-making processes within cells. Our
model successfully reproduces key features of the germ line during development
and adulthood, including a reasonable ovulation rate, correct sperm count, and
appropriate organization of the germ line into stably maintained zones. The model
highlights a previously overlooked way in which germ cell pressure may influence
gonadogenesis, and also predicts that adult germ cells might be subject to
mechanical feedback on the cell cycle akin to contact inhibition. We provide
experimental data consistent with the latter hypothesis. Finally, we present cell
trajectories and ancestry recorded over the course of a simulation. The novel
approaches and software described here link mechanics and cellular decision
making, and are applicable to modeling other developmental and stem cell systems.
PMID- 26428011
TI - Bone Behavior in Relation to the Depth of the Line of Marginal Cementation of
Prostheses on Morse Cone Implants: Radiographic Evaluation in a Dog Model.
AB - PURPOSE: This study was aimed at radiographically evaluating the effect of 3
different depths of the cementation line of prosthetic crowns on the bone
response around Morse cone implants. MATERIAL AND METHODS: Five dogs underwent
extractions of the lower premolars; after 3 months, placement of 30 implants, 3
mm apical to the bone level, was performed. Prefabricated cylinders of alumina,
used as abutments, with 3 different transmucosal extension were cemented to the
implants with zinc oxide-eugenol cement, determining the depth of the cementation
lines (1.5 mm apically, and 0.5 and 2.5 mm coronally, respectively, to the bone
level). In the control group, implants and abutments were placed without crowns,
therefore, with no cementation line. RESULTS: The results showed no statistically
significant differences between the control and test groups regarding the
different depths of the cementation line both mesially (P = 0.18) and distally (P
= 0.50). CONCLUSION: Different depths of cementation did not affect the behavior
of marginal bone, indicating that crowns can be cemented with zinc oxide-eugenol
cement at any distance or even at the bone level without disturbing bone healing
around Morse cone implants.
PMID- 26428010
TI - Opposing Shh and Fgf signals initiate nasotemporal patterning of the zebrafish
retina.
AB - The earliest known determinants of retinal nasotemporal identity are the
transcriptional regulators Foxg1, which is expressed in the prospective nasal
optic vesicle, and Foxd1, which is expressed in the prospective temporal optic
vesicle. Previous work has shown that, in zebrafish, Fgf signals from the dorsal
forebrain and olfactory primordia are required to specify nasal identity in the
dorsal, prospective nasal, optic vesicle. Here, we show that Hh signalling from
the ventral forebrain is required for specification of temporal identity in the
ventral optic vesicle and is sufficient to induce temporal character when
activated in the prospective nasal retina. Consequently, the evaginating optic
vesicles become partitioned into prospective nasal and temporal domains by the
opposing actions of Fgfs and Shh emanating from dorsal and ventral domains of the
forebrain primordium. In absence of Fgf activity, foxd1 expression is established
irrespective of levels of Hh signalling, indicating that the role of Shh in
promoting foxd1 expression is only required in the presence of Fgf activity. Once
the spatially complementary expression of foxd1 and foxg1 is established, the
boundary between expression domains is maintained by mutual repression between
Foxd1 and Foxg1.
PMID- 26428012
TI - Effects of Abutment Removal and Reconnection on Inflammatory Cytokine Production
Around Dental Implants.
AB - OBJECTIVES: The purpose of this study was to examine effects of abutment change
on inflammatory cytokine production around implants. MATERIALS AND METHODS: Ten
partially edentulous patients with a mean age of 60 years were recruited and
divided into 2 groups. External Branemark implants with anodic oxidized surface
were installed and submerged in all patients. In the control group, the healing
abutments were delivered at the second surgery, and they were removed more than 3
times till the final prosthesis delivery. In the test group, the final abutments
were delivered at the second surgery. At different time points during the
treatment, periimplant crevicular fluid was collected, and proinflammatory
cytokines (interleukin-1beta [IL-1beta] and tumor necrosis factor [TNF]-alpha)
were measured with enzyme-linked immunosorbent assay. The bone level was measured
on the radiograms and clinical indices were also taken. RESULTS: All implants
were osseointegrated. In the test group, IL-1beta level and probing depths were
less in test group patients compared with the control group patients, whereas TNF
alpha level and bone level were not different between the groups. CONCLUSION:
Although TNF-alpha and bone levels were not significantly different, delivering
final abutment at the second surgery would induce less inflammation in the
tissues around the implant.
PMID- 26428013
TI - Erratum to: Optical properties and bandgap evolution of ALD HfSiOxfilms.
PMID- 26428014
TI - Characterization and Evaluation of Reverse Osmosis Membranes Modified with Ag2O
Nanoparticles to Improve Performance.
AB - The objective of this work was to prepare and characterize a new and highly
efficient modified membrane by in situ interfacial polymerization on porous
polysulfone supports. The process used m-phenylenediamine and trimesoyl chloride
in hexane, incorporating silver oxide Ag2O nanoparticles of varied concentrations
from 0.001 to 0.1 wt%. Ag2O nanoparticles were prepared at different sizes
varying between 20 and 50 nm. The modified membranes were characterized by X-ray
diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray
spectroscopy (EDX), atomic force microscopy (AFM), transmission electron
microscopy (TEM), and contact angle measurement. The results showed a smooth
membrane surface and average surface roughness from 31 to 74 nm. Moreover,
hydrophilicity improved and the contact angle decreased to 41 degrees at 0.009
wt% silver oxide. The performances of the developed membranes were investigated
by measuring permeate fluxes and salt rejection capability by passing NaCl
solutions (2000 ppm) through the membranes at 225 psi. The results showed that
the flux increased from 26 to 40.5 L/m(2) h, while the salt rejection was high,
at 99 %, with 0.003 wt% Ag2O nanoparticles.
PMID- 26428015
TI - Systematic Control of Self-Assembled Au Nanoparticles and Nanostructures Through
the Variation of Deposition Amount, Annealing Duration, and Temperature on Si
(111).
AB - The size, density, and configurations of Au nanoparticles (NPs) can play
important roles in controlling the electron mobility, light absorption, and
localized surface plasmon resonance, and further in the Au NP-assisted
nanostructure fabrications. In this study, we present a systematical
investigation on the evolution of Au NPs and nanostructures on Si (111) by
controlling the deposition amount (DA), annealing temperature (AT), and dwelling
time (DT). Under an identical growth condition, the morphologies of Au NPs and
nanostructures drastically evolve when the DA is only slightly varied, based on
the Volmer-Weber and coalescence models: i.e. I: mini NPs, II: mid-sized round
dome-shaped Au NPs, III: large Au NPs, and IV: coalesced nanostructures. With the
AT control, three distinctive ranges are observed: i.e., NP nucleation, Au NPs
maturation and melting. The gradual dimensional expansion of Au NPs is always
compensated with the density reduction, which is explained with the thermodynamic
theory. The DT effect is relatively minor on Au NPs, a sharp contrast to other
metallic NPs, which is discussed based on the Ostwald-ripening.
PMID- 26428016
TI - Evaluation of High-Performance Curcumin Nanocrystals for Pulmonary Drug Delivery
Both In Vitro and In Vivo.
AB - This paper focused on formulating high-performance curcumin spray-dried powders
for inhalation (curcumin-DPIs) to achieve a high lung concentration. Curcumin
DPIs were produced using wet milling combined with the spray drying method. The
effects of different milling times on particle size and aerodynamic performance
were investigated. The curcumin-DPIs were characterized by scanning electron
microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray
diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and in vitro
dissolution. Furthermore, the in vivo pharmacokinetic behavior and tissue
distribution after pulmonary administration were also evaluated. Results showed
that the drug dissolution was significantly enhanced by processing into curcumin
DPIs. The aerodynamic results indicated that the DPIs displayed a good aerosol
performance. The plasma curcumin concentration was obviously enhanced by
inhalation, and most of the curcumin-DPIs were deposited in the lung. This study
demonstrated that inhalation was an effective way to carry drug to the lung, and
curcumin-DPIs were hopeful for lung cancer treatment in the future.
PMID- 26428017
TI - Ag2S/CdS/TiO2 Nanotube Array Films with High Photocurrent Density by Spotting
Sample Method.
AB - Ag2S/CdS/TiO2 hybrid nanotube array films (Ag2S/CdS/TNTs) were prepared by
selectively depositing a narrow-gap semiconductor-Ag2S (0.9 eV) quantum dots
(QDs)-in the local domain of the CdS/TiO2 nanotube array films by spotting sample
method (SSM). The improvement of sunlight absorption ability and photocurrent
density of titanium dioxide (TiO2) nanotube array films (TNTs) which were
obtained by anodic oxidation method was realized because of modifying
semiconductor QDs. The CdS/TNTs, Ag2S/TNTs, and Ag2S/CdS/TNTs fabricated by
uniformly depositing the QDs into the TNTs via the successive ionic layer
adsorption and reaction (SILAR) method were synthesized, respectively. The X-ray
powder diffraction (XRD), scanning electron microscopy (SEM), transmission
electron microscopy (TEM), and X-ray photoelectron spectrum (XPS) results
demonstrated that the Ag2S/CdS/TNTs prepared by SSM and other films were
successfully prepared. In comparison with the four films of TNTs, CdS/TNTs,
Ag2S/TNTs, and Ag2S/CdS/TNTs by SILAR, the Ag2S/CdS/TNTs prepared by SSM showed
much better absorption capability and the highest photocurrent density in UV-vis
range (320~800 nm). The cycles of local deposition have great influence on their
photoelectric properties. The photocurrent density of Ag2S/CdS/TNTs by SSM with
optimum deposition cycles of 6 was about 37 times that of TNTs without
modification, demonstrating their great prospective applications in solar energy
utilization fields.
PMID- 26428018
TI - A new immunoreactive recombinant protein designated as rBoSA2 from Babesia ovis:
Its molecular characterization, subcellular localization and antibody recognition
by infected sheep.
AB - Ovine babesiosis, caused by the intra-erythrocytic protozoan parasite Babesia
ovis, is an infectious and economically important tick-borne disease of sheep.
Diagnostic testing is an essential tool used for the control of the disease. In
order to identify and characterize the immunoreactive proteins which are useful
in serological diagnosis of the disease, a complementary DNA (cDNA) expression
library was constructed from B. ovis merozoite mRNA. A cDNA clone designated as
BoSA2 was identified by immunoscreening of a cDNA library using immune sheep
serum. The sequence of the BoSA2 cDNA had a partial open reading frame of 1156
nucleotides encoding a polypeptide of 384 amino acid residues. Theoretical
molecular mass for the mature protein was 43.5 kDa. The sequence of the BoSA2 was
inserted into the expression vector pGEX-4T-1 and then expressed in Escherichia
coli DH5alpha cells as a glutathione S-transferase (GST)-tagged fusion protein.
This recombinant fusion protein (rBoSA2) was purified by GST-affinity
chromatography. Immunoreactivity of the rBoSA2 was evaluated by indirect enzyme
linked immunosorbent assay (ELISA) using the sera from the animals naturally and
experimentally infected with B. ovis. ELISA results demonstrated that this
antigen was useful for the diagnosis of ovine babesiosis. The localization of the
BoSA2 protein was shown in and on the parasite and in the cytoplasm of the
infected erythrocyte by confocal laser microscope. To our knowledge, rBoSA2 is
the second immunoreactive recombinant protein of B. ovis until the present.
PMID- 26428019
TI - SSRI use during pregnancy.
AB - The Society of Maternal and Fetal Medicine recently had a conference on the use
of medications during pregnancy, delivery, and breast-feeding. One of the most
important topics covered during that 2-day conference was major depression (MDD)
and the use of Serotonin Selective Reuptake Inhibitors (SSRIs). This article will
review the current state of knowledge about MDD during and immediately after
pregnancy and treatment with SSRIs during pregnancy and breast-feeding.
PMID- 26428020
TI - FDA drug labeling for pregnancy and lactation drug safety monitoring systems.
AB - The product label required by the FDA for every drug approved for marketing in
the US is a legal document that originates with the company that wants to market
the drug, but it must be approved by the FDA. Despite the recognized limitations
of registries, the FDA's new labeling rule, effective from July 1, 2015, has
given the data available from post-marketing surveillance priority in the new
label. For this information to be maximally useful to both providers and
consumers, providers must refer as many exposed consumers as possible to the
registries, preferably prior to knowledge of the outcomes of the pregnancies.
Consumers need to cooperate with the registries to share their health information
with as much detail as possible with the registries. It will take years to
accumulate a meaningful quantity of information in many of the registries, but
they promise to be our best hope for useful counseling information in the future.
PMID- 26428021
TI - Efficacy and Safety of Paclitaxel-Coated Balloon for the Treatment of In-Stent
Restenosis in High-Risk Patients.
AB - In-stent restenosis (ISR) is a major cause of failure of percutaneous coronary
intervention. The efficacy and safety of drug-coated balloon (DCB) in patients
with high-risk clinical features are largely unknown. We enrolled 82 consecutive
patients at high risk of bleeding with angiographically significant (diameter
stenosis >= 50%) ISR of bare metal stent (BMS) or drug-eluting stent (DES),
treated with paclitaxel-coated balloon. All patients presented at least one of
the following criteria: high bleeding risk, neoplasm, chronic inflammatory
disease, and need for noncardiac surgery. Dual antiplatelet therapy was indicated
for 4 weeks after the procedure. At angiographic follow-up, overall late lumen
loss was 0.24 +/- 0.32 mm, with no significant difference between BMS-ISR and DES
ISR (0.25 +/- 0.35 vs 0.22 +/- 0.30 mm, p = 0.714). The Kaplan-Meier estimate for
major adverse clinical events-free survival at 3 years was 81.4% (82.3% in BMS
ISR vs 79.4% in DES-ISR, log-rank p = 0.866). No stent thrombosis has been
recorded. In conclusion, the use of paclitaxel-coated balloon seems to be
associated with favorable outcomes after percutaneous coronary intervention for
BMS-ISR or DES-ISR in patients with high-risk clinical features and could be
considered as a reasonable option in the presence of systemic co-morbidities and
contraindications to long-term dual antiplatelet therapy.
PMID- 26428023
TI - Obstructive sleep apnea and coronary artery calcium with special emphasis on
obesity.
PMID- 26428022
TI - Comparison of aortic root anatomy and calcification distribution between Asian
and Caucasian patients who underwent transcatheter aortic valve implantation.
AB - The current transcatheter aortic valve implantation (TAVI) devices have been
designed to fit Caucasian and Latin American aortic root anatomies. We evaluated
the racial differences in aortic root anatomy and calcium distribution in
patients with aortic stenosis who underwent TAVI. We conducted a multicenter
study of 4 centers in Asia and Europe, which includes consecutive patients who
underwent TAVI with preprocedural multidetector computed tomography. Quantitative
assessment of aortic root dimensions, calcium volume for leaflet, and left
ventricular outflow tract were retrospectively performed in a centralized core
laboratory. A total of 308 patients (Asian group, n = 202; Caucasian group, n =
106) were analyzed. Compared to Caucasian group, Asian group had smaller annulus
area (406.3 +/- 69.8 vs 430.0 +/- 76.8 mm(2); p = 0.007) and left coronary cusp
diameter (30.2 +/- 3.2 vs 31.1 +/- 3.4 mm; p = 0.02) and lower height of left
coronary artery ostia (12.0 +/- 2.5 vs 13.4 +/- 3.4 mm; p <0.001). Of baseline
anatomic characteristics, body height showed the highest correlation with annulus
area (Pearson correlation r = 0.64; p <0.001). Co-existence of lower height of
left coronary artery ostia (<12 mm) and small diameter of left coronary cusp (<30
mm) were more frequent in Asian group compared with Caucasian group (35.6% vs
20.8%; p = 0.02). In contrast, there were no differences in calcium volumes of
leaflet (367.2 +/- 322.5 vs 359.1 +/- 325.7 mm(3); p = 0.84) and left ventricular
outflow tract (8.9 +/- 23.4 vs 10.1 +/- 23.8 mm(3); p = 0.66) between 2 groups.
In conclusion, judicious consideration will be required to perform TAVI for short
patients with lower height of left coronary artery ostia and small sinus of
Valsalva.
PMID- 26428024
TI - Leg Pain in a Manual Laborer.
AB - A man admitted for deep vein thrombosis of his leg is found to have an important
unrelated electrocardiographic abnormality. In the second paragraph, either
reinsert the comma after V1 in the fifth line or remove the comma after
enlargement in the fourth line.
PMID- 26428025
TI - Effect of B-type natriuretic peptides on long-term outcomes after transcatheter
aortic valve implantation.
AB - B-type natriuretic peptide (BNP) levels are elevated in patients with aortic
stenosis (AS) and decrease acutely after replacement of the stenotic valve. The
long-term prognostic value of BNP after transcatheter aortic valve implantation
(TAVI) and the relative prognostic utility of single versus serial peri
interventional measurements of BNP and N-terminal prohormone BNP (NT-pro-BNP) are
unknown. This study sought to determine the impact of BNP levels on long-term
outcomes after TAVI and to compare the utility of BNP versus NT-pro-BNP measured
before and after intervention. We analyzed 340 patients with severe AS and
baseline pre-TAVI assessment of BNP. In 219 patients, BNP and NT-pro-BNP were
measured serially before and after intervention. Clinical outcomes over 2 years
were recorded. Patients with high baseline BNP (higher tertile >=591 pg/ml) had
increased risk of all-cause mortality (adjusted hazard ratio 3.16, 95% confidence
interval 1.84 to 5.42; p <0.001) and cardiovascular death at 2 years (adjusted
hazard ratio 3.37, 95% confidence interval 1.78 to 6.39; p <0.001). Outcomes were
most unfavorable in patients with persistently high BNP before and after
intervention. Comparing the 2 biomarkers, NT-pro-BNP levels measured after TAVI
showed the highest prognostic discrimination for 2-year mortality (area under the
curve 0.75; p <0.01). Baseline-to-discharge reduction, but not baseline levels of
BNP, was related to New York Heart Association functional improvement. In
conclusion, high preintervention BNP independently predicts 2-year outcomes after
TAVI, particularly when elevated levels persist after the intervention. BNP and
NT-pro-BNP and their serial periprocedural changes provide complementary
prognostic information for symptomatic improvement and survival.
PMID- 26428026
TI - Metabolic Dyslipidemia and Risk of Coronary Heart Disease in 28,318 Adults With
Diabetes Mellitus and Low-Density Lipoprotein Cholesterol <100 mg/dl.
AB - The risk of future coronary heart disease (CHD) in subjects with diabetes and
"metabolic dyslipidemia" (high triglyceride [TGs] and low high-density
cholesterol levels) remains a matter of concern. Little is known regarding the
risk of CHD for this phenotype with low-density lipoprotein cholesterol (LDL-C)
levels <100 mg/dl. We analyzed a diabetes cohort of 28,318 members (aged 30 to 90
years) of Kaiser Permanente Northern California during 2002 to 2011 (192,356
person-years [p-y] follow-up), with LDL-C levels <100 mg/dl and without known
CHD. We compared the incidence and hazard ratios (HRs) for CHD events in groups
using Cox models: normal high-density lipoprotein (HDL) and TG (reference; n =
7,278, 25.7%); normal HDL and high TG (>= 150 mg/dl; n = 4,484,15.8%); low HDL
(<= 50 mg/dl for women and <= 40 mg/dl for men) and normal TG (n = 4,048, 14.3%);
low HDL and high TG (metabolic dyslipidemia; n = 12,508, 44%). Patients with
metabolic dyslipidemia had the highest age-adjusted CHD events/1,000 p-y
(12.7/1,000 p-y and 19.0/1,000 p-y for women and men, respectively). After
multivariate adjustment for age, gender, ethnicity, hypertension, smoking, statin
use, duration of diabetes, and hemoglobin A1c, we observed an increased CHD risk
in women (HR 1.35, 95% confidence interval 1.14 to 1.60) and men (HR 1.62, 95%
confidence interval 1.43 to 1.83) with metabolic dyslipidemia compared to those
with normal HDL and TG. Even in subjects with an LDL-C <100 mg/dl, presence of
metabolic dyslipidemia in adults with diabetes is associated with an increased
risk of CHD. In conclusion, effective CHD prevention strategies are needed for
adults with diabetes and metabolic dyslipidemia.
PMID- 26428027
TI - Impact of hospital volume on outcomes of lower extremity endovascular
interventions: the better half?
PMID- 26428028
TI - Molecular profiling of estrogen receptor alpha and progesterone receptor
transcript variants in endometrial cancer.
AB - The human genes coding for estrogen receptor alpha (ERalpha) and progesterone
receptor (PR) express multiple receptor splice variants. Some of these receptor
variants previously have been shown to exert distinct functions in cancer cells
and might therefore differentially affect individual prognosis or therapy
response. To examine the role of ERalpha- and PR-isoforms in endometrial cancer,
we compared the expression of 19 ERalpha transcripts and 15 PR mRNA isoforms in
human endometrium and in endometrioid endometrial cancer. Expression of seven
ERalpha splice variants, total PR and of five PR transcript isoforms was found to
be significantly decreased in endometrial cancer. In endometrioid G3 tumors,
expression of 17 ERalpha and 10 PR splice variants was reduced when compared to
normal tissue. Notably, only 13% of G3 tumors did not express any ERalpha variant
and only in 25% of G3 samples no PR transcripts were expressed. Seven splice
variants were preferentially expressed in G1 and G2 tumors. In G1 tumors, a
higher number of different ERalpha and PR splice variants was expressed than in
normal endometrium, G2 or G3 tumors. Expression of total PR and of single PR
splice variants was found to be positively associated with PTEN. Our results
encourage further studies to elucidate to what extent the heterogeneous co
expression profiles we found in endometrial cancer patients differentially affect
both individual prognosis and therapy response.
PMID- 26428031
TI - Differential effects of prandial and non-prandial GLP-1 receptor agonists in type
2 diabetes therapy.
AB - In type 2 diabetes mellitus (T2DM), decreased pancreatic beta-cell function and
increased insulin resistance contribute to a steady decline in glucose
homeostasis. Maintaining levels of glycated hemoglobin <=7.0% is thought to
reduce the microvascular and possibly macrovascular complications that result if
T2DM is not properly managed. Recent guidelines have recognized the importance of
postprandial glucose (PPG) control in reducing cardiovascular risks, and have
recommended a more patient-centered approach. Glucagon-like peptide-1 receptor
agonists (GLP-1 RAs) mimic the action of the endogenous gastrointestinal hormone
GLP-1 to activate the insulin response in pancreatic beta cells in a glucose
dependent manner. Prandial GLP-1 RAs have a short plasma half-life and are
particularly effective at targeting PPG elevations, whereas long-acting non
prandial GLP-1 RAs are more effective at reducing fasting plasma glucose. These
differences highlight the potential for treatment with these agents to be
tailored to the need of individual patients and their glycemic imbalance. All GLP
1 RAs are being evaluated in long-term cardiovascular outcome trials. To date,
the only cardiovascular trial that has been completed is the ELIXA trial for
lixisenatide, which was found to meet the pre-specified criterion of non
inferiority versus placebo in terms of cardiovascular outcomes.
PMID- 26428032
TI - Versatile Particle-Based Route to Engineer Vertically Aligned Silicon Nanowire
Arrays and Nanoscale Pores.
AB - Control over particle self-assembly is a prerequisite for the colloidal
templating of lithographical etching masks to define nanostructures. This work
integrates and combines for the first time bottom-up and top-down approaches,
namely, particle self-assembly at liquid-liquid interfaces and metal-assisted
chemical etching, to generate vertically aligned silicon nanowire (VA-SiNW)
arrays and, alternatively, arrays of nanoscale pores in a silicon wafer. Of
particular importance, and in contrast to current techniques, including
conventional colloidal lithography, this approach provides excellent control over
the nanowire or pore etching site locations and decouples nanowire or pore
diameter and spacing. The spacing between pores or nanowires is tuned by
adjusting the specific area of the particles at the liquid-liquid interface
before deposition. Hence, the process enables fast and low-cost fabrication of
ordered nanostructures in silicon and can be easily scaled up. We demonstrate
that the fabricated VA-SiNW arrays can be used as in vitro transfection platforms
for transfecting human primary cells.
PMID- 26428033
TI - Stimuli-Triggered Activity of Nanoreactors by Biomimetic Engineering Polymer
Membranes.
AB - The development of advanced stimuli-responsive systems for medicine, catalysis,
or technology requires compartmentalized reaction spaces with triggered activity.
Only very few stimuli-responsive systems preserve the compartment architecture,
and none allows a triggered activity in situ. We present here a biomimetic
strategy to molecular transmembrane transport by engineering synthetic membranes
equipped with channel proteins so that they are stimuli-responsive. Nanoreactors
with triggered activity were designed by simultaneously encapsulating an enzyme
inside polymer compartments, and inserting protein "gates" in the membrane. The
outer membrane protein F (OmpF) porin was chemically modified with a pH
responsive molecular cap to serve as "gate" producing pH-driven molecular flow
through the membrane and control the in situ enzymatic activity. This strategy
provides complex reaction spaces necessary in "smart" medicine and for biomimetic
engineering of artificial cells.
PMID- 26428034
TI - Social gradients in health for Pakistani and White British women and infants in
two UK birth cohorts.
AB - OBJECTIVES: This study aims to examine social gradients in low birth weight
(LBW), preterm birth, smoking during pregnancy and maternal health for women and
infants of Pakistani origin and White British women and infants in the UK.
DESIGN: The sample included women and singleton infants from the Born in Bradford
(BiB) study (n = 8181) and the first sweep of the Millennium Cohort Study (MCS)
(n = 8980). Social gradients in health for four measures of socioeconomic status
(SES): maternal education, means-tested benefits, financial situation, and
occupation of the father were analysed in multivariate regression models
adjusting for maternal age and parity. RESULTS: For White British mothers and
infants in the MCS sample, social gradients in health were observed for at least
three out of four measures of SES for each health outcome (p for trend <.01).
Similar trends were found for White British mothers and infants in the BiB
sample, although these were less likely to be significant. There were few
associations between measures of SES and outcomes in the Pakistani samples. The
strongest evidence of a social gradient in health for Pakistani women was
demonstrated with the self-reported measure of financial situation, in relation
to mental health (p for trend <.001 in both cohorts). CONCLUSION: This study
describes a lack of social gradients in health for Pakistani women and infants
and discusses potential explanations for this finding.
PMID- 26428036
TI - Secukinumab (AIN457) for the treatment of psoriasis.
AB - Psoriasis is a chronic inflammatory disease with a multifactorial origin that
appears in patients with genetic predisposition and is induced by environmental
factors, and characterized by alterations in the innate and adaptive immunity. IL
17A is one of the specific cytokines involved in the pathogenesis of psoriasis
and its inhibition is highly effective in the treatment of patients with moderate
and severe psoriasis. Secukinumab is a monoclonal antibody that specifically
binds to IL-17A and inhibits the interaction to its receptor, and it has
demonstrated its efficacy and safety in the treatment of psoriasis. Phase II and
III clinical trials indicate that > 80% of the patients receiving secukinumab
achieve Psoriasis Area Severity Index (PASI) 75 at week 12. In the Phase III
efficacy of response and safety of two fixed secukinumab regimens in psoriasis
trial, PASI 75 rates were 81.6% with 300 mg secukinumab, 71.6% with 150 mg
secukinumab and 4.5% with placebo, and responses were maintained up to 52 weeks
in the majority of patients. In the Phase III Full Year Investigative Examination
Of Secukinumab versus Etanercept Using Two Dosing Regimens To Determine Efficacy
in Psoriasis study, the efficacy of secukinumab was compared to etanercept. The
results indicate that both doses of secukinumab (150 and 300 mg) showed superior
efficacy compared with etanercept throughout the study; PASI 75 rates at week 12
were 77.1% with 300 mg secukinumab, 67% with 150 mg of secukinumab, 44% with
etanercept and 4.9% with placebo. PASI 90 and PASI 100 were 54 and 24% with
secukinumab 300 mg and 21 and 4% with etanercept at week 12. At week 52, PASI 90
continued to be higher in the secukinumab group (65%) compared with the
etanercept group (33%). Regarding safety, the most common side effects were
nasopharyngitis and headache. The rate of infections was higher with secukinumab
than placebo. This was especially the case for Candida infections, which were
more common in the secukinumab group (4.7% with secukinumab 300 mg and 2.3% with
secukinumab 150 mg), but all cases were resolved with conventional treatment.
Secukinumab is a well-tolerated treatment that has demonstrated efficacy in
treating moderate-to-severe plaque psoriasis. Nevertheless, long-term studies are
necessary to confirm Phase II and Phase III data.
PMID- 26428035
TI - Influence of Spinal Cord Integrity on Gait Control in Human Spinal Cord Injury.
AB - Background Clinical trials in spinal cord injury (SCI) primarily rely on
simplified outcome metrics (ie, speed, distance) to obtain a global surrogate for
the complex alterations of gait control. However, these assessments lack
sufficient sensitivity to identify specific patterns of underlying impairment and
to target more specific treatment interventions. Objective To disentangle the
differential control of gait patterns following SCI beyond measures of time and
distance. Methods The gait of 22 individuals with motor-incomplete SCI and 21
healthy controls was assessed using a high-resolution 3-dimensional motion
tracking system and complemented by clinical and electrophysiological evaluations
applying unbiased multivariate analysis. Results Motor-incomplete SCI patients
showed varying degrees of spinal cord integrity (spinal conductivity) with severe
limitations in walking speed and altered gait patterns. Principal component (PC)
analysis applied on all the collected data uncovered robust coherence between
parameters related to walking speed, distortion of intralimb coordination, and
spinal cord integrity, explaining 45% of outcome variance (PC 1). Distinct from
the first PC, the modulation of gait-cycle variables (step length, gait-cycle
phases, cadence; PC 2) remained normal with respect to regained walking speed,
whereas hip and knee ranges of motion were distinctly altered with respect to
walking speed (PC 3). Conclusions In motor-incomplete SCI, distinct clusters of
discretely controlled gait parameters can be discerned that refine the evaluation
of gait impairment beyond outcomes of walking speed and distance. These findings
are specifically different from that in other neurological disorders (stroke,
Parkinson) and are more discrete at targeting and disentangling the complex
effects of interventions to improve walking outcome following motor-incomplete
SCI.
PMID- 26428037
TI - Behavioural interventions for diabetes yield modest benefits, reviews find.
PMID- 26428038
TI - Funding medical education: should we follow a different model to general higher
education? Commentary.
AB - ISSUE: There has been much recent discussion on the funding of medical education.
There has also been much discussion about the funding of higher education more
generally. EVIDENCE: The topics of discussion have included the rising costs of
education; who should pay; the various potential models of funding; and how best
to ensure maximum returns from investment. IMPLICATIONS: Medical education has
largely followed the emerging models of funding for higher education. However
there are important reasons why the funding models for higher education may not
suit medical education. These reasons include the fact that medical education is
as important to the public as it is to the learner; the range of funding sources
available to medical schools; the strict regulation of medical education; and the
fact that the privatisation and commercialisation of higher education may not
been in keeping with the social goals of medical schools and the agenda of
diversification within the medical student population.
PMID- 26428039
TI - Environmental health literacy within the Italian Asbestos Project: experience in
Italy and Latin American contexts. Commentary.
AB - The adoption of multidisciplinary approaches to foster scientific research in
public health and strengthen its impact on society is nowadays unavoidable.
Environmental health literacy (EHL) may be defined as the ability to search for,
understand, evaluate, and use environmental health information to promote the
adoption of informed choices, the reduction of health risks, the improvement of
quality of life and the protection of the environment. Both public health and
environmental health literacy involve access to and dissemination of scientific
information (including research findings), individual and collective decision
making and critical thinking. Specific experiences in environmental health
literacy have been developed within the Italian National Asbestos Project
(Progetto Amianto) in Latin American countries where the use of asbestos is still
permitted, and in Italy where a specific effort in EHL has been dedicated to the
risks caused by the presence of fluoro-edenite fibers in the town of Biancavilla
(Sicily). Taking into account the different geographical and socio-economic
contexts, both public health and environmental health literacy were addressed to
a wide range of stakeholders, within and outside the health domain.
PMID- 26428040
TI - Diabetes: a case study on strengthening health care for people with chronic
diseases. Preface.
PMID- 26428041
TI - Quality indicators for diabetes prevention programs in health care targeted at
people at high risk.
AB - OBJECTIVE: Type 2 diabetes can be efficiently prevented by lifestyle intervention
provided for people at high diabetes risk. The aim of this paper was to conduct a
literature search on existing quality indicators for type 2 diabetes prevention
and to collate and present a set of indicators that could be applied in European
countries with different health care systems and cultures. METHODS: Scientific
and grey literature was searched for relevant studies using electronic databases.
We also hand searched previous systematic reviews and reference lists of relevant
articles. RESULTS: The only publication identified was the report presenting the
results from the IMAGE project. The IMAGE indicators were used as the basis for
the proposed indicators. CONCLUSIONS: Publications on quality indicators of
diabetes prevention programmes are scarce. The quality indicators presented here
are a first step toward the definition of a core set of European indicators to
monitor and improve the quality of diabetes prevention.
PMID- 26428042
TI - Health promotion interventions in type 2 diabetes.
AB - AIM: To present the most common quality criteria in health promotion
interventions in type 2 diabetes mellitus (T2DM). METHODS: A systematic
literature search was conducted to identify review articles, health technology
assessments and policy reports of evaluated health promotion interventions in
T2DM. A descriptive analysis of study characteristics and evaluation criteria are
presented. RESULTS: Seven studies met the inclusion criteria. The findings
indicate that the most common health promotion interventions used in T2DM are
initiatives targeting health care professionals. The main ambition of the
programs was to increase the collaboration between health care professionals and
patients, and between health care centres, program managers and community
stakeholders. CONCLUSIONS: This investigation extends our knowledge of the most
common health promotion interventions in T2DM and which structure, process and
outcome measurements that are reported in such interventions. Future research
could usefully explore how the effectiveness of multicomponent and complex
interventions may be evaluated and extend the association of these factors into
other settings and in relation to other lifestyle related chronic diseases.
PMID- 26428043
TI - Education and health professionals training programs for people with type 2
diabetes: a review of quality criteria.
AB - OBJECTIVE: To contribute to the development of a set of quality criteria for
patient education and health professionals training that could be applied in
European countries. METHODS: Literature review quality criteria, pre-selection
based on a comparison of the criteria, peer group and expert based selection of
the criteria. RESULTS: 14 quality criteria were selected: goals, rationale,
target group, setting, scheduling of the education/training sessions,
environmental requirements, qualification of the trainers/educators, core
components of the educator/trainer's role, curriculum, education methods,
education didactics, monitoring of the effectiveness and quality of the program,
implementation level and source of funding. DISCUSSION: A set of preliminary
quality criteria for patient education and health professionals training was
developed, which could be applied in European countries.
PMID- 26428044
TI - National Diabetes Plans: can they support changes in health care systems to
strengthen diabetes prevention and care?
AB - Healthcare systems do not fit well with the "modern" patient, who has a right to
autonomy and self-determination. The services that are designed and delivered in
policy contexts are not prone to encourage innovation. National Diabetes Plans,
defined as "any formal strategy for improving diabetes policy, services and
outcomes that encompass structured and integrated or linked activities which are
planned and co-ordinated nationally and conducted at the national, regional, and
local level", may hold a great potential not only to improve prevention and care
for type 2 diabetes, but also for transforming healthcare delivery. Today,
changes to adapt healthcare delivery tend to be implemented within existing
provider structures, with limited understanding of specific context, structures,
processes and potential for change. National Diabetes Plan can be a diagnostic
tool for barriers, can be a driver for planning the change, and can help develop
capacities and competences that are needed to strengthen healthcare systems to
better address health promotion and chronic diseases.
PMID- 26428045
TI - Cancer burden trends in Umbria region using a joinpoint regression.
AB - INTRODUCTION: The analysis of the epidemiological data on cancer is an important
tool to control and evaluate the outcomes of primary and secondary prevention,
the effectiveness of health care and, in general, all cancer control activities.
MATERIALS AND METHODS: The aim of the this paper is to analyze the cancer
mortality in the Umbria region from 1978 to 2009 and incidence from 1994-2008.
Sex and site-specific trends for standardized rates were analyzed by "joinpoint
regression", using the surveillance epidemiology and end results (SEER) software.
RESULTS: Applying the jointpoint analyses by sex and cancer site, to incidence
spanning from 1994 to 2008 and mortality from 1978 to 2009 for all sites, both in
males and females, a significant joinpoint for mortality was found; moreover the
trend shape was similar and the joinpoint years were very close. In males
standardized rate significantly increased up to 1989 by 1.23% per year and
significantly decreased thereafter by -1.31%; among females the mortality rate
increased in average of 0.78% (not significant) per year till 1988 and afterward
significantly decreased by -0.92% per year. Incidence rate showed different
trends among sexes. In males was practically constant over the period studied
(not significant increase 0.14% per year), in females significantly increased by
1.49% per year up to 2001 and afterward slowly decreased (-0.71% n.s. estimated
annual percent change - EAPC). CONCLUSIONS: For all sites combined trends for
mortality decreased since late '80s, both in males and females; such behaviour is
in line with national and European Union data. This work shows that, even
compared to health systems that invest more resources, the Umbria public health
system achieved good health outcomes.
PMID- 26428046
TI - The influence of patients' complexity and general practitioners' characteristics
on referrals to outpatient health services in an Italian region.
AB - BACKGROUND: Patient referrals to outpatient health services may affect both
health outcomes and health expenditures. General practitioners (GP) have a
crucial role in driving the use of outpatient services and recognizing factors
which affect referrals is important for health managers and planners. OBJECTIVES:
We investigated patient- and physician-related determinants of patient referrals
in an Italian region. METHODS: This was cross-sectional study based on the
individual linkage of administrative databases from the health information system
of the Friuli Venezia Giulia region. For each GP of the region, the association
of the number of patient referrals to different types of outpatient services with
the proportion of patients with chronic conditions, with the number of hospital
admissions and drug prescriptions in 2012, and with GP's characteristics was
investigated through multilevel multivariable Poisson regression models. RESULTS:
Some chronic conditions (e.g., cancer, autoimmune diseases, endocrine diseases,
digestive system diseases) were positively associated with the number of
referrals, as were hospital admissions and drug prescriptions. Time since GP's
graduation was inversely related with referrals. CONCLUSION: Patient complexity
and GP's experience affect referral rates. These factors should be considered in
case of a reorganization of the general practice structure in Friuli Venezia
Giulia.
PMID- 26428047
TI - Recent entomological enquiry on mosquito fauna in Circeo National Park.
AB - The present study was carried out in Circeo National Park (Lazio region, Central
Italy), in order to collect data about mosquito (Diptera, Culicidae) fauna in a
protected area for biodiversity. From 2003 to 2004 seasonal surveys allowed to
collect and to identify 380 larvae and 713 adult mosquitoes in 6 sites. A total
of 15 mosquito species belonging to 6 genera were recorded; the most abundant
species were Culex pipens Linnaeus, 1758 known as the main West Nile virus
vector, Ochlerotatus detritus (Haliday, 1933) and Culiseta annulata (Dhrank,
1776). Present data show a noteworthy number of other mosquito species, even if
less abundant, reflecting the considerable environmental richness. Respect to the
past collections of Anophelinae mosquitoes carried out in the same area once
affected by malaria, the present research represents the first monitoring of the
whole Culicidae Family in Circeo National Park, up to now. This paper reports the
collected data as a first base for a future checklist in this protected area.
PMID- 26428048
TI - Mechanical qualification of collagen membranes used in dentistry.
AB - AIM: The aim of this work is the qualification of commercially available collagen
membranes in a comparative manner. The natural origin of collagen makes
standardization difficult. Nevertheless, through dimensional and mechanical
measures it is possible to mechanically qualify collagen membranes, and compare
them. METHODS: Three commercially available collagen membranes used in Guided
Bone Regeneration (GBR) and in Guided Tissue Regeneration (GTR) techniques,
namely Bio-Gide, Collprotect and Jason, were chosen for the comparison. Quasi
static (tensile tests) and time-dependent (stress relaxation test) mechanical
tests together with a functional test (tear test) were done to determine the
responses of collagen membranes under different loading conditions. RESULTS: The
tested membranes exhibited different behaviours, different deformability values
and thickness, Jason being the thinnest and Bio-Gide the thickest. Similar
differences were also observed in terms of surface density. DISCUSSION: Even
though clinical observations were not within the aim of this study, our findings
indicate that a better understanding of the correlation between mechanical
properties and thickness could lead to a more rational design and use of these
membranes in the face of specific clinical cases.
PMID- 26428049
TI - Antihypertensive drug use during pregnancy: a population based study.
AB - PURPOSE: The study aimed at assessing if the European guideline on the use of
antihypertensive drugs (AD) in pregnancy are followed in clinical practice. We
also evaluated the association between the use of non-recommended drugs and
individual characteristics. METHODS: This study analyzed a cohort of 86 171
singleton deliveries occurring between 2009-2010 in the Lombardy region, Italy.
Women with first prescription of AD during pregnancy were considered as incident
users. Methyldopa, labetalol and nifedipine were considered as "recommended
drugs"; all other AD were considered as "non-recommended". Odds Ratio and 95%
confidence intervals were estimated. RESULTS: Among the 1009 patients (1.2%)
exposed to AD during pregnancy, 675 (66.9%) were incident users. Among the
incident users, 31% received non-recommended drugs; this proportion decreased to
18% among women who started treatment in the third trimester. Women with at least
four concomitant diseases had an elevated risk of receiving non-recommended drugs
in pregnancy (OR 2.68; 95% CI 1.10-6.73). CONCLUSIONS: Exposure to recommended
antihypertensives increased during pregnancy. Nevertheless, a fraction of users
that continued or began treatment with non-recommended medications was still
present.
PMID- 26428050
TI - An ethics for the living world: operation methods of Animal Ethics Committees in
Italy.
AB - INTRODUCTION AND OBJECTIVES: Coinciding with the recent implementation in Italy
of the "Directive 2010/63/EU, regarding the protection of animals used for
scientific purposes", the Authors would like to analyse the topic of the
introduction of ethical committees for animal experimentation in Italy. This
paper furthermore aims to underline some critical aspects concerning the actions
taken by Italian institutions to comply with the provisions of EU. RESULTS AND
DISCUSSION: The implementation of the recent Italian law (Decreto Legislativo n.
26 on 4 March 2014 Implementation of the Directive 2010/63/EU on the protection
of animals used for scientific purposes) leans towards a restrictive
interpretation of the European provisions about composition and responsibilities
of "Ethical Committee for Animal Experimentation". In the composition of the
bodies mentioned, we note a tendency to restrict the composition to few
professional figures contemplated by Italian law, without guaranteeing the
independence of each committee; also, an absence of hierarchical relationship
between a research institution and his committee is apparent. Moreover, a
critical aspect is the lack of decision-making powers of these new organisms in
terms of ethical evaluation of protocols and research projects. CONCLUSIONS: What
EU legislation imposes on the member states is to set up an animal-welfare body
(art. 26). This represents a strong incentive for Italy to follow the steps of
many other European Countries, where ad hoc ethical committees have been working
for a long time. The proper functioning of these bodies may contribute to
guarantee the safety and welfare of the animals inside the laboratories, and to
balance the protection of animal life and the interests of research.
PMID- 26428051
TI - Human papilloma virus (HPV) genotypes prevalence in a region of South Italy
(Apulia).
AB - INTRODUCTION: Since human papillomavirus (HPV) is the central casual factor in
cervical cancer, understanding the epidemiology and geographical area
distribution of the most prevalent HPV genotypes constitutes an important step
towards development of strategies of prevention. AIM: The aim of this study was
to investigate the prevalence of HPV infection and to determine HPV types
distribution among 822 HPV positive women and some sexual male partners in Apulia
(Italy). METHODS: HPV DNA detection and genotyping was performed by nested-PCR
for the L1 region and reverse line blot hybridization allowing the specific
detection of 24 HPV genotyping both high risk (HR) and low risk (LR). RESULTS:
The most prevalent HPV genotypes were HPV 16 (35%), HPV 31 (16%) HPV 6 (9%), HPV
58 and 66 (7%), followed by HPV 33 (6%), HPV 18 and 56 (4%), HPV 70 and 45 (3%),
HPV 53 and 11 (2%). Currently 1.5% of tested specimens remained unclassified.
Multiple infections with at last two different high- risk HPV genotypes were
observed in 10% of specimens. CONCLUSIONS: This finding adds knowledge to HPV
epidemiological investigation, and addresses further studies aimed to consider
public health for identifying groups at risk for cervical cancer.
PMID- 26428052
TI - Patient satisfaction surveys and care quality: a continuum conundrum.
PMID- 26428053
TI - Infectious complications in patients with newly diagnosed multiple myeloma: A
complication from the past?
AB - Infectious complications are an important risk factor for early mortality in
patients with multiple myeloma. However, data about the impact and severity of
infections in these patients in the era of new therapies have not been properly
analyzed. This review has reviewed the incidence and severity of infections
complications and infection-related mortality during induction treatment in
patients with newly diagnosed myeloma receiving regimens with new drugs within
randomized trials. The results show that infections are still a major cause of
morbidity, especially among elderly patients receiving immunomodulatory drugs
seen in up to 28% of patients in some trials vs less than 10% among transplant
eligible patients. Overall infection-related mortality ranged from 0-7% in
transplant-ineligible patients, with no infection-related deaths in the majority
of the trials including younger patients. Strategies directed to further reduce
these complications and a better knowledge of their impact in patients treated
outside clinical trials are needed.
PMID- 26428055
TI - Spatio-temporal patterning of arginyl-tRNA protein transferase (ATE) contributes
to gametophytic development in a moss.
AB - The importance of the arginyl-tRNA protein transferase (ATE), the enzyme
mediating post-translation arginylation of proteins in the N-end rule degradation
(NERD) pathway of protein stability, was analysed in Physcomitrella patens and
compared to its known functions in other eukaryotes. We characterize ATE:GUS
reporter lines as well as ATE mutants in P. patens to study the impact and
function of arginylation on moss development and physiology. ATE protein
abundance is spatially and temporally regulated in P. patens by hormones and
light and is highly abundant in meristematic cells. Further, the amount of ATE
transcript is regulated during abscisic acid signalling and downstream of auxin
signalling. Loss-of-function mutants exhibit defects at various levels, most
severely in developing gametophores, in chloroplast starch accumulation and
senescence. Thus, arginylation is necessary for moss gametophyte development, in
contrast to the situation in flowering plants. Our analysis further substantiates
the conservation of the N-end rule pathway components in land plants and
highlights lineage-specific features. We introduce moss as a model system to
characterize the role of the NERD pathway as an additional layer of complexity in
eukaryotic development.
PMID- 26428056
TI - A note on bias of measures of explained variation for survival data.
AB - Papers evaluating measures of explained variation, or similar indices, almost
invariably use independence from censoring as the most important criterion. And
they always end up suggesting that some measures meet this criterion, and some do
not, most of the time leading to a conclusion that the first is better than the
second. As a consequence, users are offered measures that cannot be used with
time-dependent covariates and effects, not to mention extensions to repeated
events or multi-state models. We explain in this paper that the aforementioned
criterion is of no use in studying such measures, because it simply favors those
that make an implicit assumption of a model being valid everywhere. Measures not
making such an assumption are disqualified, even though they are better in every
other respect. We show that if these, allegedly inferior, measures are allowed to
make the same assumption, they are easily corrected to satisfy the 'independent
from-censoring' criterion. Even better, it is enough to make such an assumption
only for the times greater than the last observed failure time tau, which, in
contrast with the 'preferred' measures, makes it possible to use all the modeling
flexibility up to tau and assume whatever one wants after tau. As a consequence,
we claim that some of the measures being preferred as better in the existing
reviews are in fact inferior.
PMID- 26428057
TI - Sodium tanshinone IIA sulfonate affects Marek's disease virus replication by
inhibiting gB expression.
AB - CONTEXT: Previous studies demonstrated that sodium tanshinone IIA sulfonate (STS)
could inhibit MDV replication in vitro. The mechanism about how STS inhibits MDV
replication is still not well understood. OBJECTIVE: In this study, we evaluated
the effect of STS on gB gene/protein of Marek's disease virus (MDV). MATERIALS
AND METHODS: The concentration of 0.25 mg/ml of STS was used in this study.
Meanwhile, 0.25 mg/ml of acyclovir (ACV) was used as a positive control. About 9
11-d-old embryonated specific-pathogen-free (SPF) chicken eggs were used to
prepare CEF cells. CEF cells were infected with MDV 2 h, followed by treatment
with STS. Real-time PCR and western blot assay were used to measure the gB (UL27)
gene/protein expression in STS treatment group at 24, 48, 72, and 96 h post
infection. RESULTS: Compared with MDV control, the gB gene copies were
significantly decreased in STS and ACV treatment groups at 72 h and 96 h (p <
0.05), both in the DNA and in the mRNA level. Furthermore, the expression of gB
protein was also inhibited by STS at 24, 72, and 96 h. DISCUSSION AND CONCLUSION:
Our study demonstrated that STS could effectively inhibit the MDV replication by
suppressing gB gene/protein expression in cell culture.
PMID- 26428058
TI - Successful use of etanercept in a case of toxic epidermal necrolysis induced by
rituximab.
PMID- 26428059
TI - A Eu(II)-Containing Cryptate as a Redox Sensor in Magnetic Resonance Imaging of
Living Tissue.
AB - The Eu(II) ion rivals Gd(III) in its ability to enhance contrast in magnetic
resonance imaging. However, all reported Eu(II)-based complexes have been studied
in vitro largely because the tendency of Eu(II) to oxidize to Eu(III) has been
viewed as a major obstacle to in vivo imaging. Herein, we present solid- and
solution-phase characterization of a Eu(II)-containing cryptate and the first in
vivo use of Eu(II) to provide contrast enhancement. The results indicate that
between one and two water molecules are coordinated to the Eu(II) core upon
dissolution. We also demonstrate that Eu(II)-based contrast enhancement can be
observed for hours in a mouse.
PMID- 26428060
TI - Selective hydrogenolysis of raw glycerol to 1,2-propanediol over Cu-ZnO catalysts
in fixed-bed reactor.
AB - The catalytic properties of Cu-ZnO catalysts for glycerol hydrogenolysis to 1,2
propanediol (1,2-PDO) were tested in a fixed-bed reactor at 250 degrees C and
2.0 MPa H2. The relation between composition, surface properties, and catalytic
performance of glycerol hydrogenation of Cu-ZnO catalysts was studied using
nitrogen adsorption (BET methods), XRD, H2 temperature-programmed reduction, and
N2O chemisorptions. It was found that there was a close link between the surface
CuO amount of Cu-ZnO catalyst and the reactivity for glycerol hydrogenation. The
Cu-ZnO catalyst (Cu/Zn = 1.86) which had the highest surface Cu amount showed the
best catalytic activity for glycerol hydrogenolysis. Furthermore, Cu-ZnO catalyst
presented good stability and remarkable catalytic activity for glycerol
hydrogenolysis to 1,2-PDO using raw glycerol derived from the fat saponification
as feedstock.
PMID- 26428061
TI - The link between flowering time and stress tolerance.
AB - Evolutionary success in plants is largely dependent on the successful transition
from vegetative to reproductive growth. In the lifetime of a plant, flowering is
not only an essential part of the reproductive process but also a critical
developmental stage that can be vulnerable to environmental stresses. Exposure to
stress during this period can cause substantial yield losses in seed-producing
plants. However, it is becoming increasingly evident that altering flowering time
is an evolutionary strategy adopted by plants to maximize the chances of
reproduction under diverse stress conditions, ranging from pathogen infection to
heat, salinity, and drought. Here, recent studies that have revealed new insights
into how biotic and abiotic stress signals can be integrated into floral pathways
are reviewed. A better understanding of how complex environmental variables
affect plant phenology is important for future genetic manipulation of crops to
increase productivity under the changing climate.
PMID- 26428062
TI - Gene networks controlling petal organogenesis.
AB - One of the biggest unanswered questions in developmental biology is how growth is
controlled. Petals are an excellent organ system for investigating growth control
in plants: petals are dispensable, have a simple structure, and are largely
refractory to environmental perturbations that can alter their size and shape. In
recent studies, a number of genes controlling petal growth have been identified.
The overall picture of how such genes function in petal organogenesis is
beginning to be elucidated. This review will focus on studies using petals as a
model system to explore the underlying gene networks that control organ
initiation, growth, and final organ morphology.
PMID- 26428063
TI - Founder-cell-specific transcription of the DORNROSCHEN-LIKE promoter and
integration of the auxin response.
AB - Transcription of the DORNROSCHEN (DRNL) promoter marks lateral-organ founder
cells throughout Arabidopsis development, from cotyledons to flowers or floral
organs. In the inflorescence apex, DRNL::GFP depicts incipient floral phyllotaxy,
and organs in the four floral whorls are differentially prepatterned: the sepals
unidirectionally along an abaxial-adaxial axis, the four petals and two lateral
stamens in two putative morphogenetic fields, and the medial stamens subsequently
in a ring-shaped domain, before two groups of carpel founder cells are specified.
The dynamic DRNL transcription pattern is controlled by three enhancer elements,
which redundantly and synergistically control qualitative or quantitative aspects
of expression, and differentially integrate the auxin response in Arabidopsis
inflorescence and floral meristems. The high sequence conservation of all three
enhancer elements among the Brassicaceae is striking, which suggests that densely
packed cis-regulatory elements are conserved to recruit multiple transcription
factors, including auxin response factors, into higher-order enhanceosome
complexes. The spatial organization of the enhancers is also conserved, by a
microsynteny that extends beyond the Brassicaceae, which relates to enhancer
sharing, as the distal element En1 bidirectionally serves DRNL and the upstream
At1g24600 gene; the genes are transcribed in opposite directions and possibly
comprise a conserved functional chromatin domain.
PMID- 26428064
TI - Fluctuation of Arabidopsis seed dormancy with relative humidity and temperature
during dry storage.
AB - The changes in germination potential of freshly harvested seeds of Arabidopsis
thaliana stored in various combinations of temperature and relative humidity were
investigated over 63 weeks of storage. Seeds of the wild type Col-0 and of two
mutants displaying low and high levels of dormancy, cat2-1 and mtr4-1,
respectively, were stored at harvest in 24 different environments including a
combination of eight relative humidities, from 1 to 85%, and four temperatures
(10, 15, 20, and 25 degrees C). These mutations did not influence behaviour of
seeds during storage. Primary dormant seeds did not germinate in darkness at 25
degrees C but acquired the potential to germinate at this temperature within 7
weeks when stored in relative humidities close to 50% across all temperatures.
Sorption isotherms and Arrhenius plots demonstrated that the seed moisture
content of 0.06 g H2O/g dry weight was a critical value below which dormancy
release was associated with reactions of negative activation energy and above
which dormancy release increased with temperature. Longer storage times when
relative humidity did not exceed 75-85% led to decreased germination at 25
degrees C, corresponding to the induction of secondary dormancy. Dormancy release
and induction of secondary dormancy in the dry state were associated with
induction or repression of key genes related to abscisic acid and gibberellins
biosynthesis and signalling pathways. In high relative humidity, prolonged
storage of seeds induced ageing and progressive loss of viability, but this was
not related to the initial level of dormancy.
PMID- 26428065
TI - Soil water capture trends over 50 years of single-cross maize (Zea mays L.)
breeding in the US corn-belt.
AB - Breeders have successfully improved maize (Zea mays L.) grain yield for the
conditions of the US corn-belt over the past 80 years, with the past 50 years
utilizing single-cross hybrids. Long-term improvement for grain yield under water
limited conditions has also been reported. Grain yield under water-limited
conditions depends on water use, water use efficiency, and harvest index. It has
been hypothesized that long-term genetic gain for yield could be due, in part, to
increased water capture from the soil. This hypothesis was tested using a set of
elite single-cross hybrids that were released by DuPont Pioneer between 1963 and
2009. Eighteen hybrids were grown in the field during 2010 and 2011 growing
seasons at Woodland, CA, USA. Crops grew predominantly on stored soil water and
drought stress increased as the season progressed. Soil water content was
measured to 300cm depth throughout the growing season. Significant water
extraction occurred to a depth of 240-300cm and seasonal water use was calculated
from the change in soil water over this rooting zone. Grain yield increased
significantly with year of commercialization, but no such trend was observed for
total water extraction. Therefore, the measured genetic gain for yield for the
period represented by this set of hybrids must be related to either increased
efficiency of water use or increased carbon partitioning to the grain, rather
than increased soil water uptake.
PMID- 26428068
TI - Polyfluorides and Neat Fluorine as Host Material in Matrix-Isolation Experiments.
AB - The use of neat fluorine in matrix isolation is reported, as well as the
formation of polyfluoride monoanions under cryogenic conditions. Purification
procedures and spectroscopic data of fluorine are described, and matrix shifts of
selected molecules and impurities in solid fluorine are compared to those of
common matrix gases (Ar, Kr, N2 , Ne). The reaction of neat fluorine and IR-laser
ablated metal atoms to yield fluorides of chromium (CrF5 ), palladium (PdF2 ),
gold (AuF5 ), and praseodymium (PrF4 ) has been investigated. The fluorides have
been characterized in solid fluorine by IR spectroscopy at 5 K. Also the
fluorination of Kr and the photo-dismutation of XeO4 have been studied by using
IR spectroscopy in neat fluorine. Formation of the [F5 ](-) ion was obtained by
IR-laser ablation of platinum in the presence of fluorine and proven in a Ne
matrix at 5 K by two characteristic vibrational bands of [F5 ](-) at $?tilde ?nu
$=850.7 and 1805.0 cm(-1) and its photo-behavior.
PMID- 26428066
TI - Ethylene negatively regulates transcript abundance of ROP-GAP rheostat-encoding
genes and affects apoplastic reactive oxygen species homeostasis in epicarps of
cold stored apple fruits.
AB - Apple (Malus*domestica Borkh) fruits are stored for long periods of time at low
temperatures (1 degrees C) leading to the occurrence of physiological disorders.
'Superficial scald' of Granny Smith apples, an economically important ethylene
dependent disorder, was used as a model to study relationships among ethylene
action, the regulation of the ROP-GAP rheostat, and maintenance of H2O2
homeostasis in fruits during prolonged cold exposure. The ROP-GAP rheostat is a
key module for adaptation to low oxygen in Arabidopsis through Respiratory Burst
NADPH Oxidase Homologs (RBOH)-mediated and ROP GTPase-dependent regulation of
reactive oxygen species (ROS) homeostasis. Here, it was shown that the
transcriptional expression of several components of the apple ROP-GAP machinery,
including genes encoding RBOHs, ROPs, and their ancillary proteins ROP-GEFs and
ROP-GAPs, is coordinately and negatively regulated by ethylene in conjunction
with the progressive impairment of apoplastic H2O2 homeostatic levels. RNA
sequencing analyses showed that several components of the known ROP- and ROS
associated transcriptional networks are regulated along with the ROP-GAP rheostat
in response to ethylene perception. These findings may extend the role of the ROP
GAP rheostat beyond hypoxic responses and suggest that it may be a functional
regulatory node involved in the integration of ethylene and ROS signalling
pathways in abiotic stress.
PMID- 26428067
TI - Over-expression of an S-domain receptor-like kinase extracellular domain improves
panicle architecture and grain yield in rice.
AB - The S-domain receptor kinase (SRK) comprises a highly polymorphic subfamily of
receptor-like kinases (RLKs) originally found to be involved in the self
incompatibility response in Brassica. Although several members have been
identified to play roles in developmental control and disease responses, the
correlation between SRKs and yield components in rice is still unclear. The
utility of transgenic expression of a dominant negative form of SRK, OsLSK1
(Large spike S-domain receptor like Kinase 1), is reported here for the
improvement of grain yield components in rice. OsLSK1 was highly expressed in
nodes of rice and is a plasma membrane protein. The expression of OsLSK1
responded to the exogenous application of growth hormones, to abiotic stresses,
and its extracellular domain could form homodimers or heterodimers with other
related SRKs. Over-expression of a truncated version of OsLSK1 (including the
extracellular and transmembrane domain of OsLSK1 without the intracellular kinase
domain) increased plant height and improve yield components, including primary
branches per panicle and grains per primary branch, resulting in about a 55.8%
increase of the total grain yield per plot (10 plants). Transcriptional analysis
indicated that several key genes involved in the GA biosynthetic and signalling
pathway were up-regulated in transgenic plants. However, full-length cDNA over
expression and RNAi of OsLSK1 transgenic plants did not exhibit a detectable
visual phenotype and possible reasons for this were discussed. These results
indicate that OsLSK1 may act redundantly with its homologues to affect yield
traits in rice and manipulation of OsLSK1 by the dominant negative method is a
practicable strategy to improve grain yield in rice and other crops.
PMID- 26428069
TI - Gender-related patterns and determinants of recent help-seeking for past-year
affective, anxiety and substance use disorders: findings from a national
epidemiological survey.
AB - AIMS: To examine: (1) gender-specific determinants of help-seeking for mental
health, including health professional consultation and the use of non-clinical
support services and self-management strategies (SS/SM) and; (2) gender
differences among individuals with unmet perceived need for care. METHOD:
Analyses focused on 689 males and 1075 females aged 16-85 years who met ICD-10
criteria for a past-year affective, anxiety or substance use disorder in an
Australian community-representative survey. Two classifications of help-seeking
for mental health in the previous year were created: (1) no health professional
consultation or SS/SM, or health professional consultation, or SS/SM only, and;
(2) no general practitioner (GP) or mental health professional consultation, or
GP only consultation, or mental health professional consultation. Between- and
within-gender help-seeking patterns were explored using multinomial logistic
regression models. Characteristics of males and females with unmet perceived need
for care were compared using chi-square tests. RESULTS: Males with mental or
substance use disorders had relatively lower odds than females of any health
professional consultation (adjusted odds ratio [AOR] = 0.46), use of SS/SM only
(AOR = 0.59), and GP only consultation (AOR = 0.29). Notably, males with severe
disorders had substantially lower odds than females of any health professional
consultation (AOR = 0.29) and GP only consultation (AOR = 0.14). Most correlates
of help-seeking were need-related. Many applied to both genders (e.g., severity,
disability, psychiatric comorbidity), although some were male-specific (e.g.,
past-year reaction to a traumatic event) or female-specific (e.g., past-year
affective disorder). Certain enabling and predisposing factors increased the
probability of health professional consultation for both genders (age 30+ years)
or for males (unmarried, single parenthood, reliance on government pension).
Males with unmet perceived need for care were more likely to have experienced a
substance use disorder and to want medicine or tablets or social intervention,
whereas their females peers were more likely to have experienced an anxiety
disorder and to want counselling or talking therapy. For both genders,
attitudinal/knowledge barriers to receiving the types of help wanted (e.g., not
knowing where to get help) were more commonly reported than structural barriers
(e.g., cost). CONCLUSIONS: Findings suggest a need to address barriers to help
seeking in males with severe disorders, and promote GP consultation. Exploring
gender-specific attitudinal/knowledge barriers to receiving help, and the types
of help wanted, may assist in designing interventions to increase consultation.
Mental health promotion/education efforts could incorporate information about the
content and benefits of evidence-based treatments and encourage males to
participate in other potentially beneficial actions (e.g., physical activity).
PMID- 26428071
TI - Artificial evolution of coumarin dyes for dye sensitized solar cells.
AB - The design and discovery of novel molecular structures with optimal properties
has been an ongoing effort for materials scientists. This field has in general
been dominated by experiment driven trial-and-error approaches that are often
expensive and time-consuming. Here, we investigate if a de novo computational
design methodology can be applied to the design of coumarin-based dye sensitizers
with improved properties for use in Gratzel solar cells. To address the issue of
synthetic accessibility of the designed compounds, a fragment-based assembly is
employed, wherein the combination of chemical motifs (derived from the existing
databases of structures) is carried out with respect to user-adaptable set of
rules. Rather than using computationally intensive density functional theory
(DFT)/ab initio methods to screen candidate dyes, we employ quantitative
structure-property relationship (QSPR) models (calibrated from empirical data)
for rapid estimation of the property of interest, which in this case is the
product of short circuit current (Jsc) and open circuit voltage (Voc). Since QSPR
models have limited validity, pre-determined applicability domain criteria are
used to prevent unacceptable extrapolation. DFT analysis of the top-ranked
structures provides supporting evidence of their potential for dye sensitized
solar cell applications.
PMID- 26428072
TI - A comparison of volumetric modulated arc therapy and sliding-window intensity
modulated radiotherapy in the treatment of Stage I-II nasal natural killer/T-cell
lymphoma.
AB - This article is aimed to compare the dosimetric differences between volumetric
modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for
Stage I-II nasal natural killer/T-cell lymphoma (NNKTL). Ten patients with Stage
I-II NNKTL treated with IMRT were replanned with VMAT (2 arcs). The prescribed
dose of the planning target volume (PTV) was 50Gy in 25 fractions. The VMAT plans
with the Anisotropic Analytical Algorithm (Version 8.6.15) were based on an
Eclipse treatment planning system; the monitor units (MUs) and treatment time (T)
were scored to measure the expected treatment efficiency. All the 10 patients
under the study were subject to comparisons regarding the quality of target
coverage, the efficiency of delivery, and the exposure of normal adjacent organs
at risk (OARs). The study shows that VMAT was associated with a better conformal
index (CI) and homogeneity index (HI) (both p < 0.05) but slightly higher dose to
OARs than IMRT. The MUs with VMAT (650.80 +/- 24.59) were fewer than with IMRT
(1300.10 +/- 57.12) (relative reduction of 49.94%, p = 0.00) when using 2-Gy dose
fractions. The treatment time with VMAT (3.20 +/- 0.02 minutes) was shorter than
with IMRT (7.38 +/- 0.18 minutes) (relative reduction of 56.64%, p = 0.00). We
found that VMAT and IMRT both provide satisfactory target dosimetric coverage and
OARs sparing clinically. Likely to deliver a bit higher dose to OARs, VMAT in
comparison with IMRT, is still a better choice for treatment of patients with
Stage I-II NNKTL, thanks to better dose distribution, fewer MUs, and shorter
delivery time.
PMID- 26428073
TI - Associations of pancreatic beta-cell function and insulin resistance with
microalbuminuria in type 2 diabetes.
AB - We investigate the relationships of pancreatic beta-cell function and insulin
resistance with microalbuminuria in a cross-sectional study of patients with type
2 diabetes. The study suggests insulin resistance is associated with an increased
prevalence of microalbuminuria, while improved pancreatic beta-cell function is
linked to decreased rates of microalbuminuria for those patients.
PMID- 26428070
TI - Diversity in clinical management and protocols for the treatment of major
bleeding trauma patients across European level I Trauma Centres.
AB - BACKGROUND: Uncontrolled haemorrhage is still the leading cause of preventable
death after trauma and the primary focus of any treatment strategy should be
related to early detection and control of blood loss including haemostasis.
METHODS: For assessing management practices across six European level I trauma
centres with academic interest and research in the field of coagulopathy an
online survey was conducted addressing local management practice for bleeding
trauma patients including algorithms for detection, management and monitoring
coagulation disorders and immediate interventions. Each centre provided their
locally applied massive transfusion protocol. RESULTS: All participating trauma
centres have developed and implemented a local algorithm and protocol for the
bleeding trauma patient. These are uniformly activated by clinical triggers and
deactivated once the bleeding has stopped according to clinical assessment in
combination with laboratory signs of achieved haemostasis. The severity of
coagulopathy and shock is mostly assessed via standard coagulation tests and
partially used extended viscoelastic tests. All centres have implemented the
immediate use of tranexamic acid. Initial resuscitation is started either pre
hospital or after hospital admission by using transfusion packages with pre-fixed
universal blood product combinations and ratios following the concept of "damage
control resuscitation" at which applied ratios substantially vary. Two centres
initially start with transfusion packages but with viscoelastic tests running in
parallel to quickly allow a shift towards a viscoelastic test-guided therapy.
CONCLUSION: Diversity in the management of bleeding trauma patients such as pre
hospital blood administration and routinely performed viscoelastic tests exists
even among level I trauma centres. The paucity of consensus among these centres
highlights the need for further primary research followed by clinical trials to
improve the evidence for sophisticated guidelines and strategies.
PMID- 26428074
TI - Increased return of spontaneous circulation at the expense of neurologic
outcomes: Is prehospital epinephrine for out-of-hospital cardiac arrest really
worth it?
AB - INTRODUCTION: Current guidelines for the management of out-of-hospital cardiac
arrest (OHCA) recommend the use of prehospital epinephrine by initial responders.
This recommendation was initially based on data from animal models of cardiac
arrest and minimal human data, but since its inception, more human data regarding
prehospital epinephrine in this setting are now available. Although out-of
hospital return of spontaneous circulation (ROSC) may be higher with the use of
epinephrine, worse neurologic outcomes may be associated with its use. METHODS: A
systematic review of the literature was conducted by search of databases
including PubMed, Embase, and OVID to identify studies comparing patients with
OHCA who had received epinephrine before arrival to the hospital with those who
had not. Studies were assessed for quality and bias, and data were abstracted
from studies deemed appropriate for inclusion. A meta-analysis was conducted
using a Mantel-Haenszel model for dichotomous outcomes. Outcomes studied were
prehospital ROSC, survival at 1 month, survival to discharge, and positive
neurologic outcome. RESULTS: A total of 14 studies with 655853 patients were
included for the meta-analysis. The use of epinephrine for OHCA before arrival to
the hospital was associated with a significant increase in ROSC (odds ratio,
2.86; P<.001) and a significant increase in the risk of poor neurologic outcome
at the time of discharge (odds ratio 0.51, P=.008). There was no significant
difference in survival at 1 month or survival to discharge. CONCLUSION: Use of
epinephrine before arrival to the hospital for OHCA does not increase survival to
discharge but does make it more likely for those who are discharged to have poor
neurologic outcome. There is a need for additional randomized controlled trials.
PMID- 26428075
TI - Admission hyperglycemia is associated with poor outcome after emergent coronary
bypass grafting surgery.
AB - PURPOSE: Hyperglycemia during or after cardiac surgery is a common finding that
is associated with poor outcome. Very few data, however, are available regarding
a correlation between admission blood glucose and outcomes after coronary artery
bypass grafting (CABG). Thus, the goal of the current study was to examine the
relationship between admission blood glucose and outcome after emergency CABG
surgery. MATERIALS AND METHODS: A retrospective analysis to evaluate whether
admission hyperglycemia associated with increased morbidity or mortality was
performed in patients after emergency CABG surgery. The records of all the
patients undergoing emergency CABG surgery between January 1999 and December 2010
at the University of Virginia Health System were reviewed. Postoperative in
hospital mortality and complications were considered as study end points.
RESULTS: A total of 240 patients met the final inclusion criteria. Overall
mortality was 14.1%. The median admission blood glucose in patients who died 7.4
(interquartile range, 5.9-10.1) mmol/L was significantly higher compared with
survivors 6.1 (interquartile range, 5.4-7.2; P<.01). Furthermore, 59% of the
patients who died had admission blood glucose levels higher than 6.6 mmol/L,
whereas only 35% of the patients who survived had similar blood glucose levels
(P=.01). On multivariable analysis, admission blood glucose was identified as an
independent risk factor for death after emergency CABG (P=.01; odds ratio, 1.16;
95% confidence interval, 1.04-1.29). Admission blood glucose was further
identified as independently associated with increased risk for a composite
outcome of death, postoperative renal failure or stroke (P=.01; odds ratio, 1.14;
95% confidence interval, 1.03-1.27). CONCLUSIONS: Our study shows for the first
time that admission blood glucose is correlated with increased morbidity and
mortality among patients undergoing emergency CABG surgery.
PMID- 26428076
TI - Enhanced oral healing following local mesenchymal stromal cell therapy.
PMID- 26428077
TI - Link for Injured Kids: A Patient-Centered Program of Psychological First Aid
After Trauma.
AB - OBJECTIVE: Injury, the most common type of pediatric trauma, can lead to a number
of adverse psychosocial outcomes, including posttraumatic stress disorder.
Currently, few evidence-based parent programs exist to support children
hospitalized after a traumatic injury. Using methods in evaluation and
intervention research, we completed a formative research study to develop a new
program of psychological first aid, Link for Injured Kids, aimed to educate
parents in supporting their children after a severe traumatic injury. METHODS:
Using qualitative methods, we held focus groups with parents and pediatric trauma
providers of children hospitalized at a Level I Children's Hospital because of an
injury in 2012. We asked focus group participants to describe reactions to trauma
and review drafts of our intervention materials. RESULTS: Health professionals
and caregivers reported a broad spectrum of emotional responses by their children
or patients; however, difficulties were experienced during recovery at home and
upon returning to school. All parents and health professionals recommended that
interventions be offered to parents either in the emergency department or close
to discharge among admissions. CONCLUSIONS: Results from this study strongly
indicate a need for posttrauma interventions, particularly in rural settings, to
support families of children to address the psychosocial outcomes in the
aftermath of an injury. Findings presented here describe the process of
intervention development that responds to the needs of an affected population.
PMID- 26428078
TI - Adverse effects of frailty on social functioning in older adults: Results from
the Longitudinal Aging Study Amsterdam.
AB - OBJECTIVES: The aim of this study was to examine the association between physical
frailty and social functioning among older adults, cross-sectionally and
prospectively over 3 years. STUDY DESIGN: The study sample consisted of 1115
older adults aged 65 and over from two waves of the Longitudinal Aging Study
Amsterdam, a population based study. MAIN OUTCOME MEASURES: Frailty was measured
at T1 (2005/2006) using the criteria of the frailty phenotype, which includes
weight loss, weak grip strength, exhaustion, slow gait speed and low physical
activity. Social functioning was assessed at T1 and T2 (2008/2009) and included
social network size, instrumental support, emotional support, and loneliness.
RESULTS: Cross-sectional linear regression analyses adjusted for covariates (age,
sex, educational level and number of chronic diseases) showed that pre-frail and
frail older adults had a smaller network size and higher levels of loneliness
compared to their non-frail peers. Longitudinal linear regression analyses
adjusted for covariates and baseline social functioning showed that frailty was
associated with an increase in loneliness over 3 years. However, the network size
and levels of social support of frail older adults did not further decline over
time. CONCLUSIONS: Frailty is associated with poor social functioning, and with
an increase in loneliness over time. The social vulnerability of physical frail
older adults should be taken into account in the care provision for frail older
adults.
PMID- 26428079
TI - Regulation of HIPK Proteins by MicroRNAs.
AB - INTRODUCTION: The homeodomain-interacting protein kinase (HIPK) family consists
of four evolutionarily conserved and highly related nuclear serine/threonine
kinases of recent discovery. They interact with homeobox proteins and other
transcription factors, as well as transcriptional coactivators or corepressors
depending on the cellular context. HIPK proteins are sensors for various
extracellular stimuli, which control key cellular functions such as signal
transduction to downstream effectors that regulate apoptosis, embryonic
development, DNA-damage response, and cellular proliferation. Thus, HIPKs are
involved in proliferative diseases such as cancer and fibrosis. mRNA levels and
protein stability tightly regulate expression levels of HIPKs. METHODS: Here, we
review recent works investigating the regulation of HIPKs expression by microRNAs
(miRNAs) that are involved in the control of cell proliferation, sensitivity to
chemotherapeutic drugs, epithelial-mesenchymal transition, and glucose-stimulated
insulin secretion. CONCLUSION: It appears that HIPK family members, and their
related miRNAs, may be considered as novel therapeutic targets for treating
cancer, renal fibrosis and type 2 diabetes.
PMID- 26428080
TI - Development of Integrative Map of MicroRNA Gene Regulatory Elements.
AB - Like many other omics types, miRNomics is the topic of increased research
interest. Fast accumulation of diverse biological information generates
fragmented and sometimes contradictory results. There is an urgent need for
development of protocols for systematic assembling, organization and integration
of accumulated genomics data. In the present study we developed a protocol for
connecting microRNA (miRNA) interactions into an integrative map of miRNA
regulatory elements including: upstream regulators, overlapping genomic elements
and downstream targets; miRNA-target interactions (MTIs). Data integration
(integromics) in miRNomics enables revealing miRNA regulatory networks, obtaining
new knowledge, setting more targeted hypotheses, prioritization of candidate
regions, and facilitates biomarker development.
PMID- 26428081
TI - Widening access to medicine may improve general practitioner recruitment in
deprived and rural communities: survey of GP origins and current place of work.
AB - BACKGROUND: Widening access to medicine in the UK is a recalcitrant problem of
increasing political importance, with associated strong social justice arguments
but without clear evidence of impact on service delivery. Evidence from the
United States suggests that widening access may enhance care to underserved
communities. Additionally, rural origin has been demonstrated to be the factor
most strongly associated with rural practice. However the evidence regarding
socio-economic and rural background and subsequent practice locations in the UK
has not been explored. The aim of this study was to investigate the association
between general practitioners' (GPs) socio-economic and rural background at
application to medical school and demographic characteristics of their current
practice. METHOD: The study design was a cross-sectional email survey of general
practitioners practising in Scotland. Socio-economic status of GPs at application
to medical school was assessed using the self-coded National Statistics Socio
Economic Classification. UK postcode at application was used to define urban
rural location. Current practice deprivation and remoteness was measured using
NHS Scotland defined measures based on registered patients' postcodes. RESULTS: A
survey was sent to 2050 Scottish GPs with a valid accessible email address, with
801 (41.5 %) responding. GPs whose parents had semi-routine or routine
occupations had 4.3 times the odds of working in a deprived practice compared to
those with parents from managerial and professional occupations (95 % CI 1.8
10.2, p = 0.001). GPs from remote and rural Scottish backgrounds were more likely
to work in remote Scottish practices, as were GPs originating from other UK
countries. CONCLUSION: This study showed that childhood background is associated
with the population GPs subsequently serve, implying that widening access may
positively affect service delivery in addition to any social justice rationale.
Longitudinal research is needed to explore this association and the impact of
widening access on service delivery more broadly.
PMID- 26428083
TI - Ketoacidosis associated with low-carbohydrate diet in a non-diabetic lactating
woman: a case report.
AB - INTRODUCTION: Non-diabetic ketoacidosis is a rare condition which can be caused
by starvation. Lack of glucose can force the body into ketogenesis causing a
metabolic acidosis. As previously reported in the literature, ketoacidosis might,
on rare occasions, be caused by a diet with low carbohydrate content. However, to
the best of our knowledge this is the first reported case in the literature of
ketoacidosis, in a non-diabetic patient, associated with a combination of low
carbohydrate, high fat diet and lactation. CASE PRESENTATION: A healthy non
diabetic, 32-year old white woman started a low carbohydrate, high fat diet when
she was breastfeeding her son of 10 months of age. After 10 days she was admitted
to our hospital with nausea and vomiting and a serum pH of 7.20 and base excess
of -19. Clinical signs and blood samples were compatible with ketoacidosis. She
was given fluids intravenously and insulin. No anamnestic or clinical signs of
diabetes were found. She recovered quickly and was discharged 3 days later.
CONCLUSIONS: Ketogenic diets like low carbohydrate, high fat may induce
ketoacidosis. Lactation might further aggravate the condition and can perhaps
even be the trigger into ketoacidosis. Health services should be aware of the
risks associated with ketogenic diets, and be able to recognize this serious
condition when it is presented.
PMID- 26428084
TI - An institutional approach to support the conduct and use of health policy and
systems research: The Nodal Institute in the Eastern Mediterranean Region.
AB - BACKGROUND: The use of health policy and systems research (HPSR) to support
decision making in health systems is limited in the Eastern Mediterranean Region
(EMR). This is partly due to the lack of effective initiatives to strengthen
regional HPSR capacities and promote its use in decision making. This paper
offers a structured reflection on the establishment and core functioning of a
HPSR Nodal Institute for the EMR with specific focus on the approach used to
support the conduct and use of HPSR. It seeks to gain better understanding of the
activities conducted by the Nodal Institute, the methods by which the Nodal
Institute implemented these activities, and the outcomes of these activities.
METHODS: A multi-faceted approach was implemented by the Nodal Institute in
collaboration with regional academic/research institutions, Sub-Nodes. The
overall approach was a phased one that included the selection of Sub-Nodes,
mapping of academic/research institutions in the EMR, stakeholders' meetings, and
HPSR capacity building workshops, and culminated with a regional meeting.
RESULTS: The mapping of academic/research institutions in the EMR resulted in the
identification of 50 institutions, of which only 32 were engaged in HPSR. These
institutions have the highest HPSR involvement in information/evidence (84%) and
the lowest in human resources for health (34%). Their main HPSR focus areas
included quality of healthcare services, patient safety, management of non
communicable diseases, and human resources for health. Regional HPSR challenges
among these institutions were identified. The validation and ranking
questionnaires resulted in the identification of country-specific HPSR priorities
according to stakeholders in three countries. From these results, cross-cutting
HPSR priorities among the countries related to primary healthcare, non
communicable diseases, human resources for health, as well as cross-cutting HPSR
priorities among stakeholders and according to stakeholders of the countries,
were extracted. CONCLUSION: The Nodal Institute in the EMR is a promising
initiative to support the conduct and use of HPSR in health policies. The
approach and findings reported in this paper allow for the development of
opportunities towards the building of capacity for HPSR in the region and other
countries and provide a roadmap for academic/research institutions interested in
HPSR in the region.
PMID- 26428082
TI - American Society of Blood and Marrow Transplantation, European Society of Blood
and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network,
and International Myeloma Working Group Consensus Conference on Salvage
Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma.
AB - In contrast to the upfront setting in which the role of high-dose therapy with
autologous hematopoietic cell transplantation (HCT) as consolidation of a first
remission in patients with multiple myeloma (MM) is well established, the role of
high-dose therapy with autologous or allogeneic HCT has not been extensively
studied in MM patients relapsing after primary therapy. The International Myeloma
Working Group together with the Blood and Marrow Transplant Clinical Trials
Network, the American Society of Blood and Marrow Transplantation, and the
European Society of Blood and Marrow Transplantation convened a meeting of MM
experts to: (1) summarize current knowledge regarding the role of autologous or
allogeneic HCT in MM patients progressing after primary therapy, (2) propose
guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4)
propose a research agenda, and (5) develop a collaborative initiative to move the
research agenda forward. After reviewing the available data, the expert committee
came to the following consensus statement for salvage autologous HCT: (1) In
transplantation-eligible patients relapsing after primary therapy that did NOT
include an autologous HCT, high-dose therapy with HCT as part of salvage therapy
should be considered standard; (2) High-dose therapy and autologous HCT should be
considered appropriate therapy for any patients relapsing after primary therapy
that includes an autologous HCT with initial remission duration of more than 18
months; (3) High-dose therapy and autologous HCT can be used as a bridging
strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to
be explored in the context of well-designed prospective trials that should
include new agents, such as monoclonal antibodies, immune-modulating agents, and
oral proteasome inhibitors; (5) Autologous HCT consolidation should be explored
as a strategy to develop novel conditioning regimens or post-HCT strategies in
patients with short (less than 18 months remissions) after primary therapy; and
(6) Prospective randomized trials need to be performed to define the role of
salvage autologous HCT in patients with MM relapsing after primary therapy
comparing it to "best non-HCT" therapy. The expert committee also underscored the
importance of collecting enough hematopoietic stem cells to perform 2
transplantations early in the course of the disease. Regarding allogeneic HCT,
the expert committee agreed on the following consensus statements: (1) Allogeneic
HCT should be considered appropriate therapy for any eligible patient with early
relapse (less than 24 months) after primary therapy that included an autologous
HCT and/or high-risk features (ie, cytogenetics, extramedullary disease, plasma
cell leukemia, or high lactate dehydrogenase); (2) Allogeneic HCT should be
performed in the context of a clinical trial if possible; (3) The role of
postallogeneic HCT maintenance therapy needs to be explored in the context of
well-designed prospective trials; and (4) Prospective randomized trials need to
be performed to define the role salvage allogeneic HCT in patients with MM
relapsing after primary therapy.
PMID- 26428085
TI - Molecular detection of vector-borne agents in dogs from ten provinces of China.
AB - BACKGROUND: Although many vector-borne agents are potential zoonoses and cause
substantial morbidity and mortality in dogs worldwide, there are limited data on
these organisms in dogs of China. METHODS: Quantitative PCRs for vector-borne
agents were performed to investigate their prevalences in convenience whole blood
samples obtained from 1114 dogs from 21 veterinary clinics and a commercial dog
breeding facility in ten provinces of China. In addition, the PCRs were performed
on 146 Rhipicephalus sanguineus senso lato and 37 Linognathus setosus collected
from dogs in the commercial dog breeding facility. RESULTS: DNAs of Babesia
gibsoni and B. vogeli (1.2 %), Ehrlichia canis (1.3 %), Hepatozoon canis (1.8 %)
and Theileria orientalis (0.1 %) or a closely related organism were detected in
the bloods of the dogs studied, and Babesia vogeli (3.4 %) and Ehrlichia canis
(4.1 %) in R. sanguineus senso lato. The qPCRs for Anaplasma spp., Dirofilaria
immitis and Leishmania spp. were negative for all blood samples, ticks and lice.
At least one vector-borne agent was found in dogs from 5 of the 10 provinces
investigated in this study. Overall, 4.4 % (49/1117) of the dogs studied were
positive for at least one vector-borne agent with the prevalence being highest in
the commercial breeding colony (24/97; 24.7 %). CONCLUSIONS: Our study confirms
that B. vogeli, B. gibsoni, H. canis, and E. canis occur in China. Also, we
present evidence that T. orientalis or a closely related organism can infect
dogs.
PMID- 26428086
TI - Low case notification rates of childhood tuberculosis in southern Ethiopia.
AB - BACKGROUND: Childhood tuberculosis (TB) is a public health concern causing
considerable mortality. However, control of childhood TB receives little
attention. The control efforts could be inadequate because of challenges
associated with difficulties in diagnosing the disease in children. Understanding
the burden of the disease among children is important to assess the ongoing
transmission of the disease in a community and improving TB control efforts. This
study was carried out to assess TB case notification rates (CNRs) and treatment
outcomes in children aged less than 15 years over a ten-year period. METHODS:
Data were collected from unit TB registers from all health facilities providing
TB treatment in the Sidama Zone in Ethiopia. We analysed the CNRs and treatment
outcomes by age category, gender, and place of residence. We used logistic
regression analysis to identify factors associated with treatment outcomes and to
control for confounding. RESULTS: A total of 4,656 cases of children less than 15
years of age were notified as diagnosed and treated for TB, constituting 13% of
all notified TB cases in the study area. The mean CNRs per 100,000 children less
than 15 years were 30 for all new cases of TB, 28 for rural cases, 67 for urban
cases, 28 in boys, and 32 in girls. The proportions of treatment success were 82%
for new and 77% for retreatment cases for the entire study period and increased
to 93% for new cases in 2012 (X(2) trend, P < 0.001). Children less than five
years old had a lower treatment success [adjusted odds ratio (AOR) 0.64 (95% CI,
0.52-0.80)] and higher deaths [AOR 2 (95% CI, 1.27-3.12)]. The proportion of
children who died during treatment among children in the less than 2-year-old age
group was three times higher than children in the 2 year and above age groups
[AOR 3.34 (95% CI, 1.92-5.82)]. CONCLUSION: The CNRs of childhood TB were low in
Sidama. Children less than 5 years old had a higher proportion of deaths. Efforts
need to be made to improve the diagnosis and treatment of TB among children.
PMID- 26428087
TI - Polyhydroxyalkanoates production with Ralstonia eutropha from low quality waste
animal fats.
AB - Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible polyesters
considered as alternatives to petroleum-based plastics. Ralstonia eutropha is a
model organism for PHA production. Utilizing industrially rendered waste animal
fats as inexpensive carbon feedstocks for PHA production is demonstrated here. An
emulsification strategy, without any mechanical or chemical pre-treatment, was
developed to increase the bioavailability of solid, poorly-consumable fats. Wild
type R. eutropha strain H16 produced 79-82% (w/w) polyhydroxybutyrate (PHB) per
cell dry weight (CDW) when cultivated on various fats. A productivity of 0.3g
PHB/(L * h) with a total PHB production of 24 g/L was achieved using tallow as
carbon source. Using a recombinant strain of R. eutropha that produces
poly(hydroxybutyrate-co-hydroxyhexanoate) [P(HB-co-HHx)], 49-72% (w/w) of PHA per
CDW with a HHx content of 16-27 mol% were produced in shaking flask experiments.
The recombinant strain was grown on waste animal fat of the lowest quality
available at lab fermenter scale, resulting in 45 g/L CDW with 60% (w/w) PHA per
CDW and a productivity of 0.4 g PHA/(L * h). The final HHx content of the polymer
was 19 mol%. The use of low quality waste animal fats as an inexpensive carbon
feedstock exhibits a high potential to accelerate the commercialization of PHAs.
PMID- 26428088
TI - Dissecting the functional roles of the conserved NXXE and HXE motifs of the ADP
dependent glucokinase from Thermococcus litoralis.
AB - The activity of the ADP-dependent glucokinase from Thermococcus litoralis (TlGK)
relies on the highly conserved motifs NXXE (i.e. Asn-Xaa-Xaa-Glu) and HXE (i.e.
His-Xaa-Glu). Site-directed mutagenesis of residues Glu279 (HXE) and Glu308
(NXXE) leads to enzymes with highly reduced catalytic rates. The replacement of
Glu308 by Gln increased the KM for MgADP(-) and was activated by free Mg(2+). On
the other hand, HXE mutants did not affect the KM for MgADP(-), were still
inhibited by free Mg(2+), and caused a large increase on KM for glucose and an 87
fold weaker binding of glucose onto the non-hydrolysable TlGK.AMP-AlF3 complex.
Our findings put forward the fundamental role of the HXE motif in glucose binding
during ternary complex formation.
PMID- 26428089
TI - The diagnostic utility of scintigraphy in esophageal burn: a rat model.
AB - BACKGROUND: Corrosive esophageal injury due to accidental ingestion is a serious
clinical problem in children particularly in developing countries. The present
study was conducted to evaluate the diagnostic utility of technetium-99m
pyrophosphate ((99m)Tc-PYP) scintigraphy in the early stage of esophageal burns
by using different concentrations of sodium hydroxide (NaOH) in an experimental
rat model. MATERIALS AND METHODS: Twenty-eight male Sprague-Dawley rats, weighing
200-250 g, were used in the study. Esophageal burn model was created in 21 rats
by gastrically infusion of various concentrations of NaOH. The rats were divided
randomly into three groups: mild-burn group (n = 7) received 15% NaOH, moderate
burn group (n = 7) received 30% NaOH and severe-burn group (n = 7) received 45%
NaOH. Seven rats were identified as control group and received normal saline.
Three hours after burn injury, 1-mCi (99m)Tc-PYP was administered through tail
vein. Two hours after (99m)Tc-PYP administration, static imaging with gamma
camera was performed. Then, histopathologic assessment of esophageal samples was
achieved properly. RESULTS: All NaOH-applied groups (mild, moderate, and severe)
showed a significant higher uptake ratio when compared to control group (P <
0.005). NaOH-applied groups displayed important histologic alterations such as
mucosal disintegration, edema, inflammation, and stromal damage when compared to
control group. Pearson correlation analysis revealed a significant correlation
between the (99m)Tc-PYP uptake ratio and histologic score (P < 0.0005).
CONCLUSIONS: The scintigraphic imaging may provide advantages in the early stage
of esophageal burns in some patients whom endoscopic procedure is contraindicated
because of its high risk of complications such as bleeding and perforation.
PMID- 26428090
TI - Pulmonary emphysema and tumor microenvironment in primary lung cancer.
AB - BACKGROUND: To clarify the relationship between the presence of pulmonary
emphysema and tumor microenvironment and their significance for the
clinicopathologic aggressiveness of non-small cell lung cancer. METHODS: The
subjects included 48 patients with completely resected and pathologically
confirmed stage I non-small cell lung cancer. Quantitative computed tomography
was used to diagnose pulmonary emphysema, and immunohistochemical staining was
performed to evaluate the matrix metalloproteinase (MMP) expression status in the
intratumoral stromal cells as well as the microvessel density (MVD). RESULTS:
Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17
(35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent
lymphovascular invasion, a high proliferative activity, and high postoperative
recurrence rate (all, P < 0.05). The majority of the tumors (13 of 17) arose in
patients with pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary
emphysema were also associated with a high MVD, proliferative activity, and
postoperative recurrence rate (all, P < 0.05). CONCLUSIONS: The MMP-9 expression
in intratumoral stromal cells is associated with the clinicopathologic
aggressiveness of lung cancer and is predominantly identified in tumors arising
in emphysematous lungs. Further studies regarding the biological links between
the intratumoral and extratumoral microenvironment will help to explain why lung
cancers originating in emphysematous lung tissues are associated with a poor
prognosis.
PMID- 26428092
TI - Conformation of carboxylated schizophyllan in aqueous solution.
AB - Carboxylated schizophyllan (sclerox) samples of different degrees of oxidation
were molecularly characterized by size exclusion chromatography equipped with a
multi-angle light scattering detector (SEC-MALS) in 0.10 M aqueous NaCl solution.
The molar mass distribution obtained by SEC-MALS shows that sclerox of low degree
of oxidation is dissolved mainly as the trimer, whereas the trimer and single
chain coexist in solution of sclerox of high degree of oxidation. The trimer of
sclerox is much more flexible than the fully ordered triple helix of the parent
schizophyllan and easily dissociates into single chains upon heating.
PMID- 26428091
TI - Exposure to nicotine increases nicotinic acetylcholine receptor density in the
reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice.
AB - Nearly 80% of adult smokers begin smoking during adolescence. Binge alcohol
consumption is also common during adolescence. Past studies report that nicotine
and ethanol activate dopamine neurons in the reward pathway and may increase
synaptic levels of dopamine in the nucleus accumbens through nicotinic
acetylcholine receptor (nAChR) stimulation. Activation of the reward pathway
during adolescence through drug use may produce neural alterations affecting
subsequent drug consumption. Consequently, the effect of nicotine exposure on
binge alcohol consumption was examined along with an assessment of the
neurobiological underpinnings that drive adolescent use of these drugs.
Adolescent C57BL/6J mice (postnatal days 35-44) were exposed to either water or
nicotine (200MUg/ml) for ten days. On the final four days, ethanol intake was
examined using the drinking-in-the-dark paradigm. Nicotine-exposed mice consumed
significantly more ethanol and displayed higher blood ethanol concentrations than
did control mice. Autoradiographic analysis of nAChR density revealed higher
epibatidine binding in frontal cortical regions in mice exposed to nicotine and
ethanol compared to mice exposed to ethanol only. These data show that nicotine
exposure during adolescence increases subsequent binge ethanol consumption, and
may affect the number of nAChRs in regions of the brain reward pathway,
specifically the frontal cortex.
PMID- 26428093
TI - Biophysical properties of carboxymethyl derivatives of mannan and dextran.
AB - Mannan from Candida albicans, dextran from Leuconostoc spp. and their
carboxymethyl (CM)-derivatives were tested on antioxidant and thrombolytic
activities. As antioxidant tests, protection of liposomes against OH radicals and
reducing power assay were used. Dextran and mannan protected liposomes in dose
dependent manner. Carboxymethylation significantly increased antioxidant
properties of both CM-derivatives up to concentration of 10mg/mL, higher
concentrations did not change the protection of liposomes. The reducing power of
CM-mannan (DS 0.92) was significantly lower (P<0.05) than underivatized mannan.
No reductive activity was found for dextran and CM-dextran. All CM-derivatives
demonstrated statistically significant increasing activity compared with
underivatized polysaccharides. The highest thrombolytic activity was found using
CM-mannan (DS 0.92). The clot lysis here amounted to 68.78 +/- 6.52% compared
with 0.9% NaCl control (18.3 +/- 6.3%). Three-dimensional surface profiles of
mannan, dextran, and their CM-derivatives were compared by atomic force
microscopy.
PMID- 26428094
TI - Characterization and comparison of polysaccharides from Lycium barbarum in China
using saccharide mapping based on PACE and HPTLC.
AB - Water-soluble polysaccharides from 51 batches of fruits of L. barbarum
(wolfberry) in China were investigated and compared using saccharide mapping,
partial acid hydrolysis, single and composite enzymatic digestion, followed by
polysaccharide analysis by using carbohydrate gel electrophoresis (PACE) analysis
and high performance thin layer chromatography (HPTLC) analysis, respectively.
Results showed that multiple PACE and HPTLC fingerprints of partial acid and
enzymatic hydrolysates of polysaccharides from L. barbarum in China were similar,
respectively. In addition, results indicated that beta-1,3-glucosidic, alpha-1,4
galactosiduronic and alpha-1,5-arabinosidic linkages existed in polysaccharides
from L. barbarum collected in China, and the similarity of polysaccharides in L.
barbarum collected from different regions of China was pretty high, which are
helpful for the improvement of the performance of polysaccharides from L.
barbarum in functional/health foods area. Furthermore, polysaccharides from Panax
notoginseng, Angelica sinensis, and Astragalus membranaceus var. mongholicus were
successfully distinguished from those of L. barbarum based on their PACE
fingerprints. These results were beneficial to improve the quality control of
polysaccharides from L. barabrum and their products, which suggested that
saccharide mapping based on PACE and HPTLC analysis could be a routine approach
for quality control of polysaccharides.
PMID- 26428095
TI - Effect of post-treatments and concentration of cotton linter cellulose
nanocrystals on the properties of agar-based nanocomposite films.
AB - Cellulose nanocrystals (CNCs) were prepared by acid hydrolysis of cotton linter
pulp fibers and three different purification methods, i.e., without post
purification (CNC1), dialyzed against distilled water (CNC2), and neutralized
with NaOH (CNC3), and their effect on film properties was evaluated by
preparation of agar/CNCs composite films. All the CNCs were rod in shape with
diameter of 15-50 nm and length of 210-480 nm. FTIR result indicated that there
was no distinctive differences in the chemical structure between CNCs and cotton
linter cellulose fiber. No significant relationship was observed between the
sulfate content and crystallinity index of CNCs. The CNC3 showed higher thermal
stability than the other type of CNCs due to the less adverse effect on the
thermal stability of sulfate groups induced by the neutralization with NaOH. The
tensile strength (TS) of agar film increased by 15% with incorporation of 5 wt%
of CNC3, on the contrary, it decreased by 10% and 15% with incorporation of CNC1
and CNC2, respectively. Other performance properties of agar/CNCs composite films
such as optical and water vapor barrier properties showed that the CNC3 was more
effective filler than the other CNCs. In the range of concentration of CNC3
tested (1-10 wt%), inclusion of 5 wt% of CNC3 was the maximum concentration for
improving or maintaining film properties of the composite films. The
neutralization of acid hydrolyzed cellulose using NaOH was simple and convenient
for the preparation of CNC and bionanocomposite films.
PMID- 26428096
TI - Cationic guar gum orchestrated environmental synthesis for silver nano-bio
composite films.
AB - This work is meant for environmentally friendly synthesis and functional
evaluation of silver nanoparticles in a newer cationic guar biopolymer (GGAA).
Assembly of molecules in lower size range (~ 10 nm) was attained in a biopolymer
entrapped bottom-up synthesis. Guar gum is a filming biopolymer. Nanoparticles
encaged in cationic guar (GGAgnC) were preserved as films for months without any
significant effect on particle size, distribution or plasmonic intensity. The new
nano-bio-composite and films were characterized fully in FTIR, XRD, SEM and TEM
studies. Silver nanoparticles induced surface water repellency remarkably and
lowered moisture permeability. GGAgnC film water contact angle was recorded as
115 degrees while, that in case of GGAA was 59 degrees . GGAgnC expressed
intense antimicrobial activity when tested against a range of microorganisms.
Immobilized silver nanoparticles in GGAA can feasibly be used as filming
microbicidals suitable for textiles, packaging and biomedical device
applications.
PMID- 26428097
TI - Dehydration of an ethanol/water azeotrope through alginate-DNA membranes cross
linked with metal ions by pervaporation.
AB - To obtain high dehydration membranes for an ethanol/water azeotrope, dried blend
membranes prepared from mixtures of sodium alginate (Alg-Na) and sodium
deoxyribonucleate (DNA-Na) were cross-linked by immersing in a methanol solution
of CaCl2 or MaCl2. In the dehydration of an ethanol/water azeotropic mixture by
pervaporation, the effects of immersion time in methanol solution of CaCl2 or
MaCl2 on the permeation rate and water/ethanol selectivity through Alg-DNA/Ca(2+)
and Alg-DNA/Mg(2+) cross-linked membranes were investigated. Alg-DNA/Mg(2+) cross
linked membrane immersed for 12h in methanol solution of MaCl2 exhibited the
highest water/ethanol selectivity. This results from depressed swelling of the
membranes by formation of a cross-linked structure. However, excess immersion in
solution containing cross-linker led to an increase in the hydrophobicity of
cross-linked membrane. Therefore, the water/ethanol selectivity of Alg-DNA/Mg(2+)
cross-linked membranes with an excess immersion in cross-linking solution was
lowered. The relationship between the structure of Alg-DNA/Ca(2+) and Alg
DNA/Mg(2+) cross-linked membranes and their permeation and separation
characteristics during pervaporation of an ethanol/water azeotropic mixture is
discussed in detail.
PMID- 26428098
TI - Ionic dextran derivatives for removal of Fastac 10 EC from its aqueous emulsions.
AB - Separation studies of Fastac 10 EC from model emulsions by cationic
polysaccharides were followed by UV-vis spectroscopy and zeta potential
measurements. Floc size measurements at the optimum polycation dose were also
carried out using laser diffraction technology. The investigated polyelectrolytes
contained various amounts of quaternary ammonium salt groups, N-ethyl(octyl)-N,N
dimethyl-2-hydroxypropyl ammonium chloride, attached to a dextran backbone. The
effects of polycation dose, its charge density, emulsion pH and pesticide
concentration on the flocculation performance were studied. The pesticide removal
results (UV-vis spectroscopy) show that the optimum polycation dose decreased
with increasing polymer charge density and the emulsion pH and increased with
increasing pesticide concentration. The zeta potential values close to zero at
the optimum polymer dose point to contribution, mainly, from charge
neutralization mechanism for the flocculation process. The flocs size increase
with increasing pesticide concentration was also observed.
PMID- 26428099
TI - Poly(butylene succinate-co-butylene adipate)/cellulose nanocrystal composites
modified with phthalic anhydride.
AB - As a kind of biomass nanofiller for polymers, cellulose nanocrystal (CNC) has
good mechanical properties and reinforcing capability. To improve the
compatibility of poly(butylene succinate-co-butylene adipate) (PBSA)/CNC
composites, phthalic anhydride was used as a compatilizer during melt mixing,
leading to the significant improvement of the mechanical properties and thermal
stability of the composites, which is related to the better dispersion of CNC in
the composites. The addition of phthalic anhydride could accelerate the
crystallization of PBSA component as evidenced by the curves of isothermal
crystallization of the composites, but had little effect on the crystalline
polymorphs of PBSA component. The addition of phthalic anhydride could strongly
improve the hydrophobicity of the composites. The good mechanical properties,
fast crystallization and improved hydrophobicity of PBSA/CNC composites with
phthalic anhydride are favor to their practical commercial utilization.
PMID- 26428100
TI - Barrier properties of nano silicon carbide designed chitosan nanocomposites.
AB - Nano silicon carbide (SiC) designed chitosan nanocomposites were prepared by
solution technique. Fourier transform infrared spectroscopy (FTIR) and X-ray
diffraction (XRD) were used for studying structural interaction of nano silicon
carbide (SiC) with chitosan. The morphology of chitosan/SiC nanocomposites was
investigated by field emission scanning electron microscope (FESEM), and high
resolution transmission electron microscope (HRTEM). The thermal stability of
chitosan was substantially increased due to incorporation of stable silicon
carbide nanopowder. The oxygen permeability of chitosan/SiC nanocomposites was
reduced by three folds as compared to the virgin chitosan. The chemical
resistance properties of chitosan were enhanced due to the incorporation of nano
SiC. The biodegradability was investigated using sludge water. The tensile
strength of chitosan/SiC nanocomposites was increased with increasing percentage
of SiC. The substantial reduction in oxygen barrier properties in combination
with increased thermal stability, tensile strength and chemical resistance
properties; the synthesized nanocomposite may be suitable for packaging
applications.
PMID- 26428101
TI - Immunomodulatory activity on macrophage of a purified polysaccharide extracted
from Laminaria japonica.
AB - In this work, a novel water-soluble homogeneous polysaccharide (LJP-31) with a
molecular mass of 2.24 * 10(6) Da was isolated and purified from Laminaria
japonica using DEAE-cellulose and Sephacryl S500 chromatography. Results showed
that LJP-31 mainly consists of arabinose, mannose, glucose and galactose in a
molar ratio of 1.0:7.8:6.6:0.8. LJP-31 exhibited significant stimulation on
macrophages and enhanced the production of NO, TNF-alpha, IL-1beta, IL-6 and IL
10 as well as the up-regulation of their gene expressions. Western blot analysis
suggested that LJP-31 has the positive effects on the translocation of NF-kappaB
p65 from cytoplasm to nucleus and the phosphorylation of IkappaBalpha, ERK1/2,
JNK1/2 and P38 in macrophages. Flow cytometric and confocal laser-scanning
microscopy analysis indicated that toll-like receptor 4 (TLR4) was at least one
of the recognition receptors of LJP-31 on the plasma membrane of macrophages.
Taken together, LJP-31 may exert its immunostimulating potency via TLR4
activation of MAPK and NF-kappaB signaling pathways.
PMID- 26428102
TI - pH Effects on solubility, zeta potential, and correlation between antibacterial
activity and molecular weight of chitosan.
AB - Six chitosans with molecular weights (MWs) of 300, 156, 72.1, 29.2, 7.1, and 3.3
kDa were prepared by cellulase degradation of chitosan (300 kDa) and
ultrafiltration techniques. We examined the correlation between activity against
Escherichia coli and Staphylococcus aureus and chitosan MW, and provided the
underlying explanation. In acidic pH conditions, the chitosan activity increased
with increasing MW, irrespective of the temperature and bacteria tested. However,
at neutral pH, chitosan activity increased as the MW decreased, and little
activity was observed for chitosans with MW >29.2 kDa. At pH 5.0 and 6.0,
chitosans exhibited good water solubility and zeta potential (ZP) decreased with
the MW, whereas the solubility and ZP of the chitosans decreased with increasing
MW at pH 7.0. Particularly, low solubility and negative ZP values were determined
for chitosans with MW >29.2 kDa, which may explain the loss of their
antibacterial activity at pH 7.0.
PMID- 26428103
TI - Investigations of bisacodyl with modified beta-cyclodextrins: Characterization,
molecular modeling, and effect of PEG.
AB - Bisacodyl inclusion into hydroxypropyl-beta-cyclodextrin and 2,6-di-O-methyl-beta
cyclodextrin cavities was experimentally and theoretically investigated, and the
effect of PEG 4000 on these inclusions was studied. Isothermal calorimetry
titration curves indicated that the binary inclusion processes are enthalpy- and
entropy-driven. The solid-state complexes were fully characterized by FT-IR,
XRPD, DSC and SEM analyses. FT-IR, (1)H NMR, and ROESY studies provided the most
favorable encapsulation modes of binary complexes, and results were further
confirmed by molecular docking and molecular dynamics studies. The presence of
PEG 4000 slightly enhanced encapsulation efficiency, solubility and dissolution
rates of the binary complexes. In vivo studies showed that complexes with CDs
markedly accelerated gastrointestinal transit time compared with pure bisacodyl,
whereas addition of PEG 4000 showed no further significant improvement of the
bioavailability.
PMID- 26428104
TI - Effect of the molecular architecture on the thermosensitive properties of
chitosan-g-poly(N-vinylcaprolactam).
AB - A series of thermoresponsive copolymers based on chitosan-g-poly(N
vinylcaprolactam) were synthesized by amidation reaction using 4-(4,6-dimethoxy
1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as coupling reagent. The effect
of molecular architecture on the thermoresponsive properties of the graft
copolymers solutions was studied by varying the chain length of the grafted
poly(N-vinylcaprolactam), PVCL, (in the range from 4 to 26 kDa) and the spacing
between grafted chains onto the chitosan backbone. The most interesting
characteristic of these copolymers is their solubility in water at temperatures
below their lower critical solution temperature (LCST). These solutions presented
a LCST between 36 and 44 degrees C, which decreases with the spacing and length
of grafted PVCL chains onto the chitosan backbone, in contrast with the limited
decrease of the LCST of PVCL above a critical M-n value around 18 kDa. This
behavior offers tangible possibilities for the preparation and application of
sensitive bioactive formulations and "smart" drug delivery systems.
PMID- 26428105
TI - Study of quantitative interactions of potato and corn starch granules with ions
in diluted solutions of heavy metal salts.
AB - Interactions of potato and corn starch granules with ions in diluted solutions of
silver, lead, copper or iron salts were investigated. It was shown experimentally
that granules accumulated the cations in amounts depending on the granule
structure and water content as well as a type of both metal and counter-ions
present in solution. Potato starch retained almost three times more cations
compared to corn starch what was proportional to the total phosphorous content in
these starches. Quantity of milligrams of cations bound by 1g of starch was
inversely correlated with the cation hydration. Ag(+), Pb(2+) and Cu(2+) were
connected in stoichiometric amounts of moles to semicrystalline and amorphous
parts of the granules. Fe(3+) ions were accumulated in higher than stoichiometric
quantities mainly in granule amorphous regions. Metal ions penetrated into
granules together with anions except nitrates which remained on surface of potato
starch granules. Cations facilitated the starch thermal decomposition in
accordance with values of their standard redox potentials. Nitrates supported
this process only in the presence of base metal cations.
PMID- 26428106
TI - The role of nanocrystalline cellulose on the microstructure of foamed castor-oil
polyurethane nanocomposites.
AB - Nanocrystalline cellulose (CNC), obtained by sulphuric acid hydrolysis, was used
to synthesize polyurethane foams (PUFs) based on a functionalized castor oil
polyol and a Methylene diphenyl diisocyanate (MDI). Formulations with varying
isocyanate index (FI) and NCO number were prepared. At 0.5 wt.%, SEM's of the
fractured surface underlined that the CNC acted both as a nucleation agent and as
a particulate surfactant with cell geometries and apparent density changing
selectively. The chemical structure of the PUF (FTIR) changed after the
incorporation of CNC by a relative change of the amount of urea, urethane and
isocyanurate groups. A low NCO number and isocyanate index contributed to the
migration of the CNC to the Hard Segment (HS), acting as reinforcement and
improving substantially the compressive mechanical properties (Ec and sigmac
improvements of 63 and 50%, respectively). For a high NCO number or isocyanate
index, the CNC migrated to the Soft Segment (SS), without causing a reinforcement
effect. The migration of the CNC was also detected with DSC, TGA and DMA,
furtherly supporting the hypothesis that a low NCO number and index contributed
both to the formation of a microstructure with a higher content of urethane
groups.
PMID- 26428107
TI - Interactions between soy protein from water-soluble soy extract and
polysaccharides in solutions with polydextrose.
AB - This study focuses on the investigation of the interactions between
polysaccharides (carrageenan and carboxymethylcellulose--CMC) and soy proteins
from the water-soluble soy extract. The influence of pH (2-7) and protein
polysaccharide ratio (5:1-40:1) on the interaction between these polyelectrolytes
was investigated in aqueous solutions with 10% of polydextrose and without
polydextrose. The studied systems were analyzed in terms of pH-solubility profile
of protein, zeta-potential, methylene blue-polysaccharide interactions,
differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy
(FTIR), and confocal laser scanning microscopy. Although the mixtures of soy
extract with both carrageenan and CMC showed dependency on the pH and protein
polysaccharide ratio, they did not present the same behavior. Both
polysaccharides modified the pH-solubility profile of the soy protein, shifting
the pH range in which the coacervate is formed to a lower pH region with the
decrease of the soy extract-polysaccharide ratio. The samples also presented
detectable differences regarding to zeta-potential, DSC, FTIR and microscopy
analyses. The complex formation was also detected even in a pH range where both
biopolymers were net-negatively charged. The changes promoted by the presence of
polydextrose were mainly detected by blue-polysaccharide interactions measures
and confocal microscopy.
PMID- 26428108
TI - Application of carboxymethylcellulose hydrogel based silver nanocomposites on
cotton fabrics for antibacterial property.
AB - In this study, fumaric acid (FA) crosslinked carboxymethylcellulose (CMC)
hydrogel (CMCF) based silver nanocomposites were coated on cotton fabric for
antibacterial property for the first time. The performance of the nanocomposite
treated cotton fabric was tested for different mixing times of hydrogel solution,
padding times and concentrations of silver. The cotton fabrics treated with CMC
hydrogel based silver nanocomposites demonstrated 99.9% reduction for both
Staphylococcus aureus (Sa) and Klebsiella pneumonia (Kp). After one cycle washing
processes of treated cotton fabric, there is no significant variation observed in
antibacterial activity. From SEM and AFM analyses, silver particles in nano-size,
homogenously distributed, were observed. The treated samples were also evaluated
by tensile strength, thermogravimetric analysis (TGA), Fourier transform infrared
spectroscopy (FTIR) analysis, fluid absorbency properties, and whiteness index.
The treatment of cotton fabric with CMCF hydrogel did not affect the whiteness
considerably, but increased the absorbency values of cotton.
PMID- 26428109
TI - How copper corrosion can be retarded--New ways investigating a chronic problem
for cellulose in paper.
AB - To better assess the stabilization effects of chemical treatments on Cu(II)
catalyzed cellulose degradation, we developed Cu(II)-containing model rag paper
with typical copper corrosion characteristics using e-beam radiation. The paper
can be prepared homogeneously and quickly compared to tedious pre-aging methods.
Using the Cu(II)-containing model rag paper, the stabilization effects of various
chemicals on Cu(II)-catalyzed degradation of cellulose were tested. Benzotriazol
was highly effective in retarding the degradation of the Cu(II)-containing model
rag paper under hot and humid aging condition, as well as under photo-oxidative
stress. Tetrabutylammonium bromide reduced Cu(II)-catalyzed degradation of
cellulose, but its efficacy was dependent on the accelerated aging conditions.
The results with the alkaline treatments and gelatin treatment suggested that
their roles in the degradation mechanisms of cellulose in the presence of Cu(II)
differ from those of benzotriazol and tetrabutylammonium bromide.
PMID- 26428110
TI - Synthesis of well-dispersed magnetic CoFe2O4 nanoparticles in cellulose aerogels
via a facile oxidative co-precipitation method.
AB - With the increasing emphasis on green chemistry, it is becoming more important to
develop environmentally friendly matrix materials for the synthesis of
nanocomposites. Cellulose aerogels with hierarchical micro/nano-scale three
dimensional network beneficial to control and guide the growth of nanoparticles,
are suitable as a class of ideal green nanoparticles hosts to fabricate
multifunctional nanocomposites. Herein, a facile oxidative co-precipitation
method was carried out to disperse CoFe2O4 nanoparticles in the cellulose
aerogels matrixes, and the cellulose aerogels were prepared from the native wheat
straw based on a green NaOH/polyethylene glycol solution. The mean diameter of
the well-dispersed CoFe2O4 nanoparticles in the hybrid aerogels is 98.5 nm.
Besides, the hybrid aerogels exhibit strong magnetic responsiveness, which could
be flexibly actuated by a small magnet. And this feature also makes this class of
magnetic aerogels possibly useful as recyclable adsorbents and some magnetic
devices. Meanwhile, the mild green preparation method could also be extended to
fabricate other miscellaneous cellulose-based nanocomposites.
PMID- 26428111
TI - Production of a low molecular weight heparin using recombinant glycuronidase
[corrected].
AB - The Delta4,5 unsaturated uronate (4-deoxy-alpha-l-threo-hex-4-eno-pyranosyluronic
acid) residue is produced through the depolymerization of heparin, heparosan, and
heparan sulfate with heparin lyases. The recovery of unsaturated uronate
containing products is necessary to prepare low molecular weight heparin (LMWH)
from heparin or heparosan. In this study, the gene of Delta4,5 and
Delta4,5(Delta20) unsaturated glycuronidase (EC# 3.2.1.56) from Pedobacter
heparinus (formerly Flavobacterium heparinum) was cloned into pMAL-c2x plasmid.
Its fusion protein with MBP was expressed in Escherichia coli TB1. After
purification, Delta4,5 unsaturated glycuronidase was evaluated. The
Delta4,5(Delta20) glycuronidase showed excellent activity on the unsaturated
bonds of the different depolymerized products from Hep I, Hep II, and Hep III on
heparin, heparosan, and heparan sulfate.
PMID- 26428112
TI - Synthesis, characterization, and controlled release of selenium nanoparticles
stabilized by chitosan of different molecular weights.
AB - Chitosan-stabilized selenium nanoparticles (SeNPs) have been reported, but there
is no information on the effect of the chitosan molecular weight on the
structure, stability, and selenium release properties of the SeNPs. Herein, we
compared the uniform Se(0) spherical nanoparticles prepared through the reduction
of seleninic acid with ascorbic acid in the presence of chitosan with different
molecular weights (Mws). We found that both low and high molecular weight
chitosan-stabilized selenium nanoparticles exhibited core-shell microstructures
with a size of about 103 nm after 30 days growing through the "bottom-up
approach" and "top-down approach," respectively. Moreover, both chitosan SeNPs
processed excellent stability towards pH and enzyme treatment. In contrast,
selenium was easily released to different extents from these two chitosan SeNPs
upon treatment with different free radicals. This makes these materials
potentially useful as oral antioxidant supplements.
PMID- 26428113
TI - Gum arabic-curcumin conjugate micelles with enhanced loading for curcumin
delivery to hepatocarcinoma cells.
AB - Curcumin is conjugated to gum arabic, a highly water soluble polysaccharide to
enhance the solubility and stability of curcumin. Conjugation of curcumin to gum
arabic is confirmed by (1)H NMR, fluorescence and UV spectroscopy studies. The
conjugate self assembles to spherical nano-micelles (270 +/- 5 nm) spontaneously,
when dispersed in aqueous medium. Spherical morphology of the self assembled
conjugate is evidenced by field emission scanning electron microscopy and
transmission electron microscopy. The self assembly of the amphiphilic conjugate
into micelle in aqueous medium significantly enhances the solubility (900 fold of
that of free curcumin) and stability of curcumin in physiological pH. The
anticancer activity of the conjugate micelles is found to be higher in human
hepatocellular carcinoma (HepG2) cells than in human breast carcinoma (MCF-7)
cells. The conjugate exhibits enhanced accumulation and toxicity in HepG2 cells
due to the targeting efficiency of the galactose groups present in gum arabic.
PMID- 26428114
TI - A molecular modeling approach to understand the structure and conformation
relationship of (GlcpA)Xylan.
AB - The structure and conformation relationships of a heteropolysaccharide
(GlcpA)Xylan in terms of various molecular weights, Xylp/GlcpA ratio and the
distribution of GlcpA along xylan chain were investigated using computer
modeling. The adiabatic contour maps of xylobiose, XylpXylp(GlcpA) and
(GlcpA)XylpXylp(GlcpA) indicated that the insertion of the side group (GlcpA)
influenced the accessible conformational space of xylobiose molecule. RIS
Metropolis Monte Carlo method indicated that insertion of GlcpA side chain
induced a lowering effect of the calculated chain extension at low GlcpA:Xylp
ratio (GlcpA:Xylp = 1:3). The chain, however, became extended when the ratio of
GlcpA:Xylp above 2/3. It was also shown that the spatial extension of the polymer
chains was dependent on the distribution of side chain: the random distribution
demonstrated the most flexible structure compared to block and alternative
distribution. The present studies provide a unique insight into the dependence of
both side chain ratio and distribution on the stiffness and flexibility of
various (GlcpA)Xylan molecules.
PMID- 26428115
TI - Coloration of cotton fibers using nano chitosan.
AB - A method of coloration of cotton fabrics with nano chitosan is proposed. Nano
chitosan were prepared using crab shell chitin nanofibers through alkaline
deacetylation process. Average nano fiber diameters of nano chitosan were 18 nm
to 35 nm and the lengths were in the range of 0.2-1.3 MUm according to the atomic
force microscope study. The degree of deacetylation of the material was found to
be 97.3%. The prepared nano chitosan dyed using acid blue 25 (2
anthraquinonesulfonic acid) and used as the coloration agent for cotton fibers.
Simple wet immersion method was used to color the cotton fabrics by nano chitosan
dispersion followed by acid vapor treatment. Scanning electron microscope and
atomic force microscope study of the treated cotton fiber revealed that the nano
chitosan were consistently deposited on the cotton fiber surface and transformed
in to a thin polymer layer upon the acid vapor treatment. The color strength of
the dyed fabrics could be changed by changing the concentration of dyed nano
chitosan dispersion.
PMID- 26428116
TI - Arsenic(V) sorption using chitosan/Cu(OH)2 and chitosan/CuO composite sorbents.
AB - The removal of As(V) ions from aqueous solution was carried out using composite
sorbents based on chitosan (as the encapsulating material) and Cu(OH)2 or CuO.
The sorbents were characterized using SEM, EDX and Zeta potential analysis.
Sorption uptake was highly dependent on pH, temperature, initial As(V)
concentration and sorbent dosage (SD): the optimum initial pH for arsenic removal
was found close to 4. The sorption isotherm was described by the Langmuir
equation. The metal ion can be bound through two different sorption sites: one
having a strong affinity for As(V) (probably Cu(OH)2 or CuO) and the other having
a lower affinity (probably the encapsulating material). The uptake kinetics was
well fitted by the pseudo-second order rate equation. The effect of temperature
was also evaluated, verifying the endothermic nature of the sorption process.
Arsenic elution was performed using a saline solution (30 g L(-1) NaCl) at pH 12.
The recycling of the sorbent was tested, maintaining a removal efficiency and a
metal recovery over 95% for five successive sorption/desorption cycles.
PMID- 26428117
TI - Enhancement of thermoplastic starch final properties by blending with poly(E
caprolactone).
AB - Final properties of two thermoplastic corn starch matrices were improved by
adding poly(E-caprolactone), PCL, at 2.5, 5, and 10% w/w. One of the
thermoplastic starch matrices was processed using water and glycerol as
plasticizers (SG) and the other one was plasticized with a mixture of glycerol
and sodium alginate (SGA). Blends were suitably processed by melt mixing and
further injected. Films obtained by thermo-compression were flexible and easy to
handle. Microstructure studies (SEM and FTIR) revealed a nice distribution of PCL
within both matrices and also a good starch-PCL compatibility, attributed to the
lower polyester concentration. The crystalline character of PCL was the
responsible of the increment in the degree of crystallinity of starch matrices,
determined by XRD. Moreover, it was demonstrated by TGA that PCL incorporation
did not affect the thermal stability of these starch-based materials. In
addition, a shift of Tg values of both glycerol and starch-rich phases to lower
values was determined by DSC and DMA tests, attributed to the PCL plasticizing
action. Besides, PCL blocking effect to visible and UV radiations was evident by
the incremented opacity and the UV-barrier capacity of the starch films. Finally,
water vapor permeability and water solubility values were reduced by PCL
incorporation.
PMID- 26428118
TI - Quince seed mucilage magnetic nanocomposites as novel bioadsorbents for efficient
removal of cationic dyes from aqueous solutions.
AB - This study investigated the potential use of quince seed mucilage (QSM) as
alternative bioadsorbents for methylene blue (MB) dye from aqueous solutions.
This novel magnetic nanocomposite adsorbent (MNCA) based on QSM was synthesized
by in situ formation of magnetic iron oxide nanoparticles into QSM solution. The
MNCAs were characterized using FTIR, SEM, TEM, XRD, and VSM. Removal of MB was
investigated by batch adsorption technique. The thermodynamic parameters suggest
that the dye adsorption process is spontaneous and exothermic in nature.
Moreover, the adsorbents showed high selectivity for the adsorption of cationic
dyes with regenerated properties. The pseudo-second-order kinetics and Langmuir
adsorption isotherm models also provide the best correlation of the experimental
data for MB adsorption. The results indicate that the MNCAs can be employed as
efficient low cost adsorbents with excellent dye adsorption performance in
wastewater treatment process.
PMID- 26428119
TI - Physical, antioxidant and structural characterization of blend films based on
hsian-tsao gum (HG) and casein (CAS).
AB - The effects of hsian-tsao gum (HG) addition on the physical properties,
antioxidant activities and structure of casein (CAS) film have been investigated.
It has been observed that HG addition provided CAS film with better mechanical
properties and resistant to moisture, stronger barrier properties against light
and higher antioxidant activities than pure CAS film. Fourier transformation
infrared (FTIR) data indicated that hydrogen bonding interactions and Maillard
reactions occurred between CAS and HG, giving rise to a more compact structure
than CAS film. The results of X-ray diffraction and differential scanning
calorimetry (DSC) indicated that CAS and HG were compatible, and addition of HG
destroyed the original crystalline domains of CAS film, and the blend films
exhibited higher glass transition temperatures than CAS film. Moreover, nuclear
magnetic resonance (NMR) analysis showed that HG addition significantly changed
the mobility of water molecule in CAS film. Especially, ratio of the high
mobility water of CAS/HG films significantly decreased as compared to CAS film.
PMID- 26428120
TI - Modification of the cellulosic component of hemp fibers using sulfonic acid
derivatives: Surface and thermal characterization.
AB - The aim of this study was to characterize the surface, morphological, and thermal
properties of hemp fibers treated with two commercially available, inexpensive,
and water soluble sulfonic acid derivatives. Specifically, the cellulosic
component of the fibers were targeted, because cellulose is not easily removed
during chemical treatment. These acids have the potential to selectively
transform the surfaces of natural fibers for composite applications. The proposed
method proceeds in the absence of conventional organic solvents and high reaction
temperatures. Surface chemical composition and signature were measured using
gravimetric analysis, X-ray photoelectron spectroscopy (XPS) and Fourier
transform infra-red spectroscopy (FTIR). XPS data from the treated hemp fibers
were characterized by measuring the reduction in O/C ratio and an increase in
abundance of the C-C-O signature. FTIR confirmed the reaction with the emergence
of peaks characteristic of disubstituted benzene and amino groups. Grafting of
the sulfonic derivatives resulted in lower surface polarity. Thermogravimetric
analysis revealed that treated fibers were characterized by lower percent
degradation between 200 and 300 degrees C, and a higher initial degradation
temperature.
PMID- 26428121
TI - Characterization of nanocellulose reinforced semi-interpenetrating polymer
network of poly(vinyl alcohol) & polyacrylamide composite films.
AB - Semi-interpenetrating polymer network (semi-IPN) of poly(vinyl
alcohol)/polyacrylamide was reinforced with various doses of nanocellulose. The
different composite films thus prepared were characterized with respect to their
mechanical, thermal, morphological and barrier properties. The composite film
containing 5 wt.% of nanocellulose showed the highest tensile strength. The semi
interpenetrating polymer network of poly(vinyl alcohol)/polyacrylamide; and its
various composites with nanocellulose were almost identical in their thermal
stability. Each of the composites however exhibited much superior stability with
respect to the linear poly(vinyl alcohol) and crosslinked polyacrylamide. The
scanning electron microscopy (SEM) and atomic force microscopy (AFM) studies
exhibited phase separated morphology where agglomerates of nanocellulose were
found to be dispersed in the matrix of the semi-IPN. The moisture vapor
transmission rate (MVTR) was the lowest for the film containing 5 wt.% of
nanocellulose.
PMID- 26428122
TI - Application of Celluclast 1.5L in apple pectin extraction.
AB - Pectins were extracted from apple pomace with Celluclast 1.5L at a dose of 25, 50
and 75 MUl per 1g of material. In obtained pectin, the galacturonic acid (GalA)
content, the neutral sugars (NS) profile, the degree of methylation (DM) and
acetylation (DAc), the molecular mass, protein, ash and polyphenol levels as well
as antioxidant and antitumor activity were determined. The lowest dose of
enzymatic preparation resulted in the yield of pectin isolation comparable with
acidic treatment (15.3%). Application of higher dose caused further, almost 4%
increase in polymer recovery. Enzymatically isolated pectin was characterised by
larger molecular mass and contained more GalA of higher DM and DAc than polymer
extracted with acid. It was also richer in protein and polyphenols, and had
different NS profile, which resulted in higher antiradical activity as well as
the ability to inhibit the proliferation and invasion of Caco-2 adenocarcinoma
cells.
PMID- 26428123
TI - Bark derived submicron-sized and nano-sized cellulose fibers: From industrial
waste to high performance materials.
AB - In this study, the use of bark as a natural source for the production of
cellulose nanofibers has been explored for the first time. The fibrillation using
bleached and unbleached cellulose fibers from the bark yielded sub-micron scale
(<1 MUm) and nanoscale fibers (<100 nm). Previous attempts to break the cross
linked lignin barrier to produce fibrillated submicron sized or nano sized
cellulose fibers with high lignin content (>20%) have never been possible from
any other sources. The maximum elastic modulus value of 15.6 GPa and tensile
strength value of 76 MPa were obtained for the films made from fibrillated bark
cellulose fibers. The water vapour barrier efficiency for these films is
comparable to nanocellulose films from other studies.
PMID- 26428124
TI - Robust and biodegradable polymer of cassava starch and modified natural rubber.
AB - The application of starch based materials for packaging purposes has attracted
significant interest because they are both cheap and renewable resources. The
study investigated the preparation and properties of a novel biopolymer sheet
produced from a blend of maleated epoxidized natural rubber (MENR) and natural
rubber-g-cassava starch (NR-g-CSt). The water resistance, toluene resistance and
elongation at break of the polymer blend were enhanced after the addition of the
MENR compared to pristine NR-g-CSt. The maximum tensile strength and thermal
stability of the NR-g-CSt/MENR blend were found in the 100:50 NR-g-CSt:MENR
blend. The novel films demonstrated good biodegradability in soil.
PMID- 26428125
TI - Ultrasonic mediated production of carboxymethyl cellulose: Optimization of
conditions using response surface methodology.
AB - In the present research the optimization of ultrasound-mediated production of
carboxymethyl cellulose under microwave irradiation, towards achieving reduction
of chemicals, time of reaction and energy was carried out. Cellulose was
extracted and treated by environmentally friendly chlorine free bleaching method
using hydrogen peroxide. Produced alpha-cellulose was characterized using Fourier
transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and
thermogravimetric/differential thermal analysis (TG/DTA). Response Surface
Methodology (RSM) was used to optimize the preparation of carboxymethyl cellulose
(CMC). Highest degree of substitution 0.74 was obtained at 240 W ultrasonic power
for 37 min followed by etherification at 490 W microwave power for 12 min.
Results show that the preparation of CMC from cotton linter using ultrasound and
microwave energy can reduce the processing time, chemicals and energy
consumption. Additionally, X-ray analysis shows that the ultrasonic energy is
able to break cellulose crystals into smaller parts compared to other methods.
SEM photographs showed that this treatment is able to remove impurities from raw
material.
PMID- 26428126
TI - Effects of pH and temperature on colloidal properties and molecular
characteristics of Konjac glucomannan.
AB - The hydrocolloidal characteristics of Konjac glucomannan (KGM) are important for
its application as a thickening and gelling agent for liquid foods. In this
study, the rheological behavior and molecular properties such as molar mass,
hydrodynamic radius and chain conformation of KGM in water were determined at
various pH levels (4.0-10.0) during heating from 20 to 80 degrees C. Acidic and
neutral conditions (pH 4.0-7.0) promoted the dispersion of KGM, and alkaline
condition at pH 10 favored its aggregation in water, while KGM maintained a
random coil conformation in the whole pH range. Associated with the pH effects
were changes in the rheological behavior during heating from 20 to 80 degrees C.
The significant differences in the colloidal and rheological characteristics were
mainly attributed to alteration of intermolecular interaction (attractive or
repulsive) rather than deacetylation at various pH levels. Deacetylation occurred
in both acidic and alkaline condition. The second virial value was positive in
acidic and negative in alkaline condition. The results showed that hydrocolloidal
characteristics of KGM in water were significantly affected by pH.
PMID- 26428127
TI - alpha,beta-Unsaturated aldehyde of hyaluronan--Synthesis, analysis and
applications.
AB - Hyaluronic acid (HA) modified with an aldehyde group (HA-CHO or HA-aldehyde) has
been extensively used for various biomedical applications. The main advantage of
the aldehyde moieties is the ability to react with a wide range of amino
compounds under physiological conditions. Reactions of aldehydes with primary
amines in water are reversible and equilibrium is thoroughly shifted towards
starting aldehyde and amine. This work presents an unique modification of HA:
alpha,beta-unsaturated aldehyde of HA (4,5-anhydro-6(GlcNAc)-oxo HA or DeltaHA
CHO), which allows the primary amines to be attached to HA more effectively in
comparison to the saturated HA-CHO. Higher hydrolytic stability is caused by the
conjugation of imine with an adjacent --C=C-- double bond. Two strategies for the
preparation of unsaturated HA-aldehyde were developed and chemical structures
were studied in details. Cross-linked materials prepared from this precursor are
biocompatible and suitable for applications in drug delivery and regenerative
medicine.
PMID- 26428128
TI - Pharmaceutical grade chondroitin sulfate: Structural analysis and identification
of contaminants in different commercial preparations.
AB - The aim of the present study was to characterize 16 pharmaceutical grade
chondroitin sulfate (CS) samples, concerning the structure and presence of
contaminants, in comparison to USP and analytical grade CS. Agarose gel
electrophoresis has shown that only 5 samples were >90% CS, while 11 contained
less than 15% CS. FACE (fluorophore-assisted carbohydrate electrophoresis)
revealed that maltodextrin was the main contaminant in nine of them, and lactose
in two. Raman spectroscopy corroborated these results. Concerning the structure
of the CS present in the five CS-rich samples, the ratios 4-sulfated:6-sulfated
disaccharides varied from 0.9 to 1.7, and their modal molecular weight was 20-29
kDa. Also, they were all contaminated by small amounts of keratan sulfate (<1%).
In conclusion, our findings indicate that the composition of CS preparations not
always corresponds to the manufacturers' descriptions, and indicate that further
characterization should be required for the registry and license of
pharmaceutical grade CS.
PMID- 26428129
TI - A three-dimensionally chitin nanofiber/carbon nanotube hydrogel network for
foldable conductive paper.
AB - We reported a highly conductive nanocomposite made with multiwalled carbon
nanotubes (MWCNTs) and chitin nanofibers (ChNFs). The MWCNTs were dispersed into
ChNFs by the simple process of vacuum-filtration, forming a three-dimensional
network structure. In this approach, MWCNT acted as a filler to introduce
electron channel paths throughout the ChNF skeleton. And then, a hybrid hydrogel
system (20 wt.% NaOH, -18 degrees C) was applied to prepare the ChNF/MWCNT gel
film followed with drying process. It is found that the resultant ChNF/MWCNT gel
film exposed much more MWCNT areas forming denser structure due to the shrinking
of ChNFs after the gelation treatment. Compared with ChNF/MWCNT film, the one
treated under hydrogel system (ChNF/MWCNT gel-film) exhibited almost twice higher
conductivity (9.3S/cm for 50 wt.% MWCNTs in gel-film; whereas 4.7S/cm for 50 wt.%
MWCNTs in film). Moreover, the facile and low-cost of this conductive paper may
have great potential in development of foldable electronic devices.
PMID- 26428130
TI - Modified hydroxyethyl starch protects cells from oxidative damage.
AB - This article describes the synthesis of novel starch-antioxidant conjugates,
which show great potential for biomedical applications to protect cells from
oxidative damage. These conjugates were synthesized by the modification of a
hydroxyethyl starch (molecular weight=200,000g/mol) with various sterically
hindered phenols that differ in radical scavenging activity. They possess
substantial radical scavenging activity toward a model free radical. It was found
that the polymer conjugate conformation depends on the antioxidant structure and
degree of substitution. We constructed the complete conformational phase behavior
for the polymers with increasing degrees of substitution from small-angle neutron
scattering data. It was observed that the conjugate conformation changes are the
result of water shifting from a thermodynamically favorable solvent to an
unfavorable one, a process that then leads to compaction of the conjugate. We
selected the conjugates that possess high substitution degree but still exhibit
coil conformation for biological studies. The high efficiency of the conjugates
was confirmed by different in vitro (hypotonic hemolysis of erythrocytes/osmotic
resistance of erythrocytes and the change of [Ca(2+)]i inside freshly isolated
cardiomyocytes) and in vivo (acute hemorrhage/massive blood loss) methods.
PMID- 26428131
TI - Agro-industrial residue from starch extraction of Pachyrhizus ahipa as filler of
thermoplastic corn starch films.
AB - Biocomposites films based on thermoplastic corn starch (TPS) containing 0.5% w/w
fibrous residue from Pachyrhizus ahipa starch extraction (PASR) were obtained by
melt-mixing and compression molding. PASR is mainly constituted by remaining cell
walls and natural fibers, revealed by Scanning Electron Microscopy (SEM).
Chemical composition of the residue indicated that fiber and starch were the
principal components. Biocomposites thermo-stability was determined by Thermo
Gravimetric Analysis. A continuous PASR-TPS interface was observed by SEM, as a
result of a good adhesion of the fibrous residue to starch matrix. Likewise,
films containing PASR presented fewer superficial cracks than TPS ones, whereas
their fracture surfaces were more irregular. Besides, the presence of PASR
increased starch films roughness, due to fibers agglomerates. Films reinforced
with PASR showed significantly lower water vapor permeability (WVP). In addition,
PARS filler increased maximum tensile strength and Young's modulus of TPS films,
thus leading to more resistant starch matrixes.
PMID- 26428132
TI - Central metabolic pathways of Aureobasidium pullulans CGMCC1234 for pullulan
production.
AB - With the purpose of understanding the metabolic network of Aureobasidium
pullulans, the central metabolic pathways were confirmed by the activities of the
key enzymes involved in different pathways. The effect of different iodoacetic
acid concentrations on pullulan fermentation was also investigated in this paper.
The activities of phosphofructokinases and glucose-6-phosphate dehydrogenase
existed in A. pullulans CGMCC1234, whereas 2-keto-3-deoxy-6-phosphogluconate
aldolase activity was not detected. We proposed that the central metabolic
pathways of A. pullulans CGMCC1234 included EMP and PPP, but no ED. Pullulan
production declined fast as the iodoacetic acid increased, while cell growth
offered upgrade firstly than descending latter tendency. Compared to the control
group, the ratio of ATP/ADP of 0.60 mM iodoacetic acid group was lower at
different stages of pullulan fermentation. The findings revealed that low
concentration of iodoacetic acid might impel carbon flux flow toward the PPP, but
reduce the flux of the EMP.
PMID- 26428133
TI - Super water-absorbing new material from chitosan, EDTA and urea.
AB - A new, super water-absorbing, material is synthesized by the reaction between
chitosan, EDTA and urea and named as CHEDUR. CHEDUR is probably formed through
the crosslinking of chitosan molecules (CH) with the EDTA-urea (EDUR) adduct that
is formed during the reaction. CHEDUR as well as the other products formed in
control reactions are characterized extensively. CHEDUR exhibits a very high
water uptake capacity when compared with chitosan, chitosan-EDTA adduct, as well
as a commercial diaper material. A systematic study was done to find the optimum
composition as well as reaction conditions for maximum water absorbing capacity.
CHEDUR can play a vital role in applications that demand the rapid absorption and
slow release of water such as agriculture, as a three in one new material for the
slow release of urea, water and other metal ions that can be attached through the
EDTA component. The other potential advantage of CHEDUR is that it can be
expected to degrade in soil based on its chitosan backbone. The new material with
rapid and high water uptake could also find potential applications as
biodegradable active ingredient of the diaper material.
PMID- 26428134
TI - Effects of crosslinking temperature and time on microstructure and stability of
cassava starch microspheres.
AB - Starch microspheres (SMs) were prepared by a water-in-water emulsion-crosslinking
technique at 4 degrees C and 30 degrees C for 1, 6, 12 and 24h; the SMs
obtained were analyzed for crosslinking density, morphology, crystalline
structure, and stability against temperature, pH, and alpha-amylase hydrolysis.
The crosslinking degree at 30 degrees C was considerably higher than that at 4
degrees C. SMs prepared at 4 degrees C for less than 12h incubation had larger
size and more porous structure as compared with those prepared at 30 degrees C,
but the morphology became comparable (spherical shape with smooth surface and
dense structure) after 24h incubation. All SMs samples displayed amorphous
structure. Stability tests revealed that the SMs were very stable under acidic
and mild basic pH; however, stability against alpha-amylase hydrolysis varied
depending on incubation temperature and time.
PMID- 26428135
TI - Development of pH sensitive microparticles of Karaya gum: By response surface
methodology.
AB - The objective of the proposed work was to prepare pH sensitive microparticles
(MP) of Karaya gum using distilled water as a solvent by spray drying technique.
Different formulations were designed, prepared and evaluated by employing
response surface methodology and optimal design of experiment technique using
Design Expert((r)) ver 8.0.1 software. SEM photographs showed that MP were
roughly spherical in shape and free from cracks. The particle size and
encapsulation efficiency for optimized MP was found to be between 3.89 and 6.5
MUm and 81-94% respectively with good flow properties. At the end of the 12th
hour the in vitro drug release was found to be 96.9% for the optimized
formulation in pH 5.6 phosphate buffer. Low prediction errors were observed for
Cmax and AUC0-infinity which demonstrated that the Frusemide IVIVC model was
valid. Hence it can be concluded that pH sensitive MP of Karaya gum were
effectively prepared by spray drying technique using aqueous solvents and can be
used for treating various diseases like chronic hypertension, Ulcerative Colitis
and Diverticulitis.
PMID- 26428136
TI - Physicochemical and functional performance of pectin extracted by QbD approach
from Tamarindus indica L. pulp.
AB - The aim of present investigation was to utilize quality by design (QbD) approach
for extraction of tamarind pectin (TP) from Tamarindus indica L. pulp employing
purity descriptors as indicator. The software generated quadratic equations
showed significant effect of polarity index as compared to pulp concentration and
boiling temperature on percentage yield and purity characteristics of TP. An
insignificant effect on purity descriptors and percentage yield of TP upon
replacement of acetone with methanol during predicted vs observed correlation
studies (being similar polarity index of 5.1) pointed towards overwhelming
influence of solvent polarity. Further, the FTIR-ATR, (1)H NMR, DSC and mass
spectroscopy suggested TP was rhamnogalacturonan pectin with no tartaric acid
content. TP was found to have significantly higher antioxidant activity as
compare to apple pomace pectin, citrus peel pectin and commercial pectin.
Overall, the physicochemical properties and antioxidant potential of TP could be
utilized as an excipient for food and pharmaceutical industry.
PMID- 26428137
TI - A water soluble beta-glucan of an edible mushroom Termitomyces heimii: Structural
and biological investigation.
AB - A water soluble beta-glucan (PS-I) with an average molecular weight ~ 1.48 *
10(5)Da was isolated from the alkaline extract of an edible mushroom Termitomyces
heimii. PS-I contained (1 -> 3)-, (1 -> 6)-, (1 -> 3, 6)-linked and terminal beta
d-glucopyranosyl moieties in a ratio of nearly 2:1:1:1. Based on the total
hydrolysis, methylation analysis, periodate oxidation, Smith degradation, partial
hydrolysis and 1D/2D NMR experiments the structure of the PS-I was elucidated. On
the basis of these experiments, the repeating unit of the polysaccharide was
found to consist of a backbone chain of two (1 -> 6)-beta-D-glucopyranosyl
residues, one of which was branched at O-3 position with the side chain
consisting of two (1 -> 3)-beta-D-glucopyranosyl and a terminal beta-D
glucopyranosyl residue. Cytotoxic effect of PS-I on human blood lymphocytes at
varied concentrations was studied. Moreover, it also exhibited potent antioxidant
activities by diminishing the ROS and NO in the nicotine stimulated lymphocytes
up to 200 MUg/ml.
PMID- 26428138
TI - Synthesis of surfactant-free hydroxypropylcellulose nanogel and its dual
responsive properties.
AB - Surfactant-free hydroxypropylcellulose (HPC) nanogels were synthesized by using
thermo-sensitive HPC as a template to form HPC/PMAA nanoscale complex. The
formation mechanism was owing to the interpolymer hydrogen bonding between HPC
and PMAA induced phase transition of HPC in aqueous media. The average size of
the resulting HPC nanogels ranges from about 98 to 241 nm. It was found that the
average size of HPC nanogels changed little with increasing polymerization
temperature below 26 degrees C, whereas it greatly increased above 26 degrees
C. When the concentration of HPC was increased from 0.1 to 0.9 wt.%, the diameter
of nanogels decreased firstly and then increased. Besides, an increasing
crosslinker BIS concentration led to a reduced size of HPC nanogels, and the
nanogels had the narrowest size distribution when its concentration was 0.1 wt.%.
In addition to intrinsic thermo-sensitivity, HPC nanogels also display pH-induced
phase transition due to pH-responsive PMAA contained in HPC nanogels. Surfactant
free, dual-responsive HPC nanogels would have promising applications in
biotechnology and nanomedicine.
PMID- 26428139
TI - Carboxymethyl chitosan/clay nanocomposites and their copper complexes:
Fabrication and property.
AB - To obtain environmentally friendly antifouling agent, an effort was made to
intercalate carboxymethyl chitosan into the interlayer of organic montmorillonite
to prepare carboxymethyl chitosan/organic montmorillonite nanocomposites and
their copper complexes. In comparison, carboxymethyl chitosan-copper complexes
were also obtained. Their structures were characterized by X-ray diffaraction,
transmittance electron microscopy and Fourier transform infrared, and their
thermal behavior and antimicrobial activity were discussed. The results revealed
that the interlayer distance of carboxymethyl chitosan/organic montmorillonite
nanocomposites enlarged with the increasing mass ratio of carboxymethyl chitosan
to organic montmorillonite, when the mass ratio was at 20:1, the layer spacing of
carboxymethyl chitosan/organic montmorillonite nanocomposites reached the maximum
of 3.68 nm. As compared to other samples, carboxymethyl chitosan/organic
montmorillonite-copper nanocomposites showed much higher thermal stability and
inhibitory activity against Escherichia coli, the lowest minimum inhibition
concentration was only 0.0003125% (w/v). The study provides a new method to find
novel antifouling agent.
PMID- 26428140
TI - beta-Cyclodextrin associated polymeric systems: Rheology, flow behavior in porous
media and enhanced heavy oil recovery performance.
AB - This proof of concept research evaluates an approach to improve the enhanced
heavy oil recovery performance of conventional polymers. Three associated
polymeric systems, based on hydrolyzed polyacrylamide, xanthan gum, and a novel
hydrophobic copolymer, were proposed in this work. The results of the
theoretically rheology study indicate that these systems offer superior
viscoelasticity and pronounced shear-thinning behavior due to the "interlocking
effect". As a result of the surfactant collaboration, the dynamic interfacial
tension between oil and polymer solution can be reduced by two orders of
magnitude. Sandpack flooding tests demonstrated the capacity of the developed
systems in mobility control during propagating in porous media, and the
adsorption behavior was represented by the thickness of the adsorbed layer. The
relationship between microscopic efficiency and capillary number indicated that
the associated systems can significantly reduce the residual oil saturation due
to the synergistic effect of the mobility reduction and surface activity, and the
overall recovery efficiency was raised by 2-20% OOIP compared to the baseline
polymers.
PMID- 26428141
TI - Antitumor and immunomodulatory activity of a water-soluble polysaccharide from
Grifola frondosa.
AB - Grifola frondosa has long been known and respected as a medically important
fungus. This study investigated the characterization, antitumor and
immunomodulatory activity of a polysaccharide named GP11 purified from G.
frondosa. The results revealed that GP11 was composed of -> 1)-D-Manp-(6 ->,-> 1)
D-Glcp-(4 ->,-> 1)-D-Galp-(6 -> and -> 2,3,6)-D-Glcp-(1 ->, with branches
attached at O-2,3 of 1,2,3,6-linked Glcp residues and terminal T-Glcp. GP11
exhibited indirect cytotoxic activity against HepG-2 cells in vitro, and it
significantly inhibited the growth of Heps cells in vivo. GP11 increased the
relative thymus and spleen weights as well as serum tumor necrosis factor-alpha
and interleukin-2 levels. GP11 stimulated tumoricidal activity and the production
of nitric oxide (NO), TNF-alpha and interleukin-1beta, and it also stimulated the
protein expression of iNOS and mRNA expression of iNOS and TNF-alpha. TLR-4 is a
potential receptor for GP11-mediated macrophage activation. The results suggested
that the antitumor activity of GP11 may be due to the improvement of immune
functions through the TLR-4-mediated up-regulation of NO and TNF-alpha.
PMID- 26428142
TI - Inhibition of wheat starch retrogradation by tea derivatives.
AB - The effect of four industrial tea derivatives (tea polyphenols [TPS], tea water
soluble extracts [TSE], tea polysaccharides [TSS], and green tea powder [GTP]),
on the retrogradation of wheat starch was investigated using texture profile
analysis (TPA), differential scanning calorimetry (DSC), rapid viscosity analysis
(RVA), and the alpha-amylase-iodine method. The addition of the four tea
derivatives resulted in decreased hardness and increased cohesiveness of the
starch gel as shown by the TPA test. The DSC data demonstrated an increase in the
enthalpy change of starch gelatinization and a decrease in the enthalpy change of
starch recrystallite dissociation. The RVA results indicated that the peak
viscosity, representing the intermolecular forces of wheat starch, was reduced
after addition of TPS, TSE, and TSS, respectively, but was increased by GTP.
Furthermore, the half crystallization time in the Avrami equation almost doubled
after the separate addition of the tea derivatives.
PMID- 26428143
TI - Inulin, a flexible oligosaccharide. II: Review of its pharmaceutical
applications.
AB - Inulin is a flexible oligosaccharide which has been used primarily in food for
decades. Recently new applications in the pharmaceutical arena were described. In
a previous review (Mensink et al. (2015). Carbohydrate Polymers, 130, 405) we
described the physicochemical characteristics of inulin, characteristics which
make inulin a highly versatile substance. Here, we review its pharmaceutical
applications. Applications of inulin that are addressed are stabilization of
proteins, modified drug delivery (dissolution rate enhancement and drug
targeting), and lastly physiological and disease-modifying effects of inulin.
Further uses of inulin include colon specific drug administration and stabilizing
and adjuvating vaccine formulations. Overall, the uses of inulin in the
pharmaceutical area are very diverse and research is still continuing,
particularly with chemically modified inulins. It is therefore likely that even
more applications will be found for this flexible oligosaccharide.
PMID- 26428144
TI - Characterization of new natural cellulosic fiber from Lygeum spartum L.
AB - Integration of new natural fibers in polymer composites field can contribute to
increase the production of natural reinforcements and expand their use into new
applications. In the present work, new cellulosic fibers were extracted from
Lygeum spartum L. plant using an eco-friendly method. The morphological, physico
chemical, thermal and mechanical properties of L. spartum L. fibers were reported
for the first time in this paper. The stem anatomy and fiber SEM micrographs
showed a strong presence of fiber cells. ATR-FTIR and X-ray analysis proved that
these fibers are rich in cellulose content with crystallinity index of 46.19%.
The thermogravimetric analysis indicates that the L. spartum fibers are thermally
stable until 220 degrees C with apparent activation energy of 68.77 kJ/mol.
Young's modulus, tensile strength and strain at failure were determined from the
single fiber tensile test as 13.2 GPa, 280 MPa, and 3.7% respectively.
PMID- 26428145
TI - Antibacterial activity and in vitro evaluation of the biocompatibility of
chitosan-based polysaccharide/polyester membranes.
AB - The antibacterial activity and biocompatibility of membranes of poly(3
hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and chitosan (CS) (PHBV)/CS) were
evaluated in this study. Maleic anhydride (MA)-grafted polyhydroxyalkanoate (PHBV
g-MA) was evaluated as an alternative to PHBV. Mouse tail skin fibroblasts (FBs)
were seeded on two series of these films to assess cytocompatibility. Collagen
and cell proliferation analyses indicated that PHBV, PHBV-g-MA and their
composite membranes were biocompatible with respect to FB proliferation. However,
FB proliferation, collagen production and the percentage of normal cells growing
on PHBV/CS membranes were greater than those for PHBV-g-MA/CS membranes. Cell
cycle and apoptosis assays by FBs on the PHBV-series membrane samples were not
affected by DNA content related to damage; i.e. rapid apoptosis/necrosis was not
observed, demonstrating the potential of PHBV/CS or PHBV-g-MA/CS membranes for
biomedical material applications. Moreover, CS-based polysaccharide enhanced the
Escherichia coli (BCRC 10239) antibacterial activity of the membranes. Membranes
of PHBV-g-MA or PHBV containing CS-based polysaccharide had better antibacterial
activity.
PMID- 26428146
TI - Effect of granule size on the properties of lotus rhizome C-type starch.
AB - Lotus rhizome C-type starch was separated into different size fractions. Starch
morphologies changed from irregular to elongated, ellipsoid, oval, and spherical
with decreasing granule size. The small- and very-small-sized fractions had a
centric hilum, and the other size fractions had an eccentric hilum. The different
size fractions all showed C-type crystallinity, pseudoplasticity and shear
thinning rheological properties. The range of amylose content was 25.6 to 26.6%,
that of relative crystallinity was 23.9 to 25.8%, that of swelling power was 29.0
to 31.4 g/g, and that of gelatinization enthalpy was 12.4 to 14.2J/g. The very
small-sized fraction had a significantly lower short-range ordered degree and
flow behavior index and higher scattering peak intensity, water solubility,
gelatinization peak temperature, gelatinization conclusion temperature,
consistency coefficient, hydrolysis degrees, and digestion rate than the large
sized fraction. Granule size significantly positively influenced short-range
ordered structure and swelling power and negatively influenced scattering peak
intensity, water solubility, hydrolysis and digestion of starch (p<0.01).
PMID- 26428147
TI - Ion-responsive liquid crystals of cellulose nanowhiskers grafted with acrylamide.
AB - In order to develop a novel application for cellulose nanowhiskers (CNW) produced
from the sulfuric acid hydrolysis of cotton, acrylamide (AM) was grafted onto the
CNW. The graft reaction of the acrylamide-grafted CNW (AM-g-CNW) was confirmed by
Fourier transform infrared spectroscopy (FTIR) and UV-vis spectroscopy. The
carbon and nitrogen contents of the AM-g-CNW were measured by elemental analysis
and X-ray photoelectron spectroscopy (XPS). The grafting ratios and average
degrees of beta-1,4-linked anhydro-D-glucose unit substitution were measured. The
thermochemical properties of the AM-g-CNW were characterized using
thermogravimetric analysis (TG). The glass transition temperatures were
determined by differential scanning calorimetry (DSC). The degrees of
crystallinity were measured by X-ray diffraction (XRD). The liquid crystalline
properties of AM-g-CNW were observed by polarizing optical microscopy (POM). AM-g
CNW had the best grafting ratio, 12.77%, when the AM/CNW molar ratio was 3,
c(K2S2O8)/n(CNW) was 0.15, the reaction temperature was 70 degrees C, and the
reaction time was 60 min. The birefringence of AM-g-CNW was responsive to
hydroxide ions, which might be useful in applications that benefit from
sensitivity towards different ionic species.
PMID- 26428148
TI - High-throughput and high-yield fabrication of uniaxially-aligned chitosan-based
nanofibers by centrifugal electrospinning.
AB - The inability to produce large quantities of nanofibers has been a primary
obstacle in advancement and commercialization of electrospinning technologies,
especially when aligned nanofibers are desired. Here, we present a high
throughput centrifugal electrospinning (HTP-CES) system capable of producing a
large number of highly-aligned nanofiber samples with high-yield and tunable
diameters. The versatility of the design was revealed when bead-less nanofibers
were produced from copolymer chitosan/polycaprolactone (C-PCL) solutions despite
variations in polymer blend composition or spinneret needle gauge. Compared to
conventional electrospinning techniques, fibers spun with the HTP-CES not only
exhibited superior alignment, but also better diameter uniformity. Nanofiber
alignment was quantified using Fast Fourier Transform (FFT) analysis. In
addition, a concave correlation between the needle diameter and resultant fiber
diameter was identified. This system can be easily scaled up for industrial
production of highly-aligned nanofibers with tunable diameters that can
potentially meet the requirements for various engineering and biomedical
applications.
PMID- 26428149
TI - Mechanically modified xanthan gum: Rheology and polydispersity aspects.
AB - Xanthan gum solutions were treated with high-pressure homogenization (HPH) in
order to provide alternative treatments to enzymatic and chemical modification of
this carbohydrate. Rheological properties of the treated and control samples were
investigated in detail to gain an understanding of functional consequences of
physical modification. The molecular structural properties were investigated via
Size exclusion chromatography (SEC) coupled with Multi-angle laser light
scattering (MALLS) and Circular dichroism (CD). Structured network of xanthan gum
solutions was lost gradually depending on the severity of the HPH treatment as
evidenced by the observed changes in the viscosity and viscoelasticity of the
treated solutions. Reduction in molecular weight and a significant increase in
polydispersity of the polymer were the expected causes of these rheological
changes. Observed increase in hydrodynamic volume upon HPH treatment was not
surprising and attributed to the loss of structured networks. Changes in the
rheological and structural characteristics of biopolymer were irreversible and
significant recovery was not detected over a period of 11 weeks.
PMID- 26428150
TI - Extrusion induced low-order starch matrices: Enzymic hydrolysis and structure.
AB - Waxy, normal and highwaymen maize starches were extruded with water as sole
plasticizer to achieve low-order starch matrices. Of the three starches, we found
that only high-amylose extrudate showed lower digestion rate/extent than starches
cooked in excess water. The ordered structure of high-amylose starches in cooked
and extruded forms was similar, as judged by NMR, XRD and DSC techniques, but
enzyme resistance was much greater for extruded forms. Size exclusion
chromatography suggested that longer chains were involved in enzyme resistance.
We propose that the local molecular density of packing of amylose chains can
control the digestion kinetics rather than just crystallinity, with the principle
being that density sufficient to either prevent/limit binding and/or slow down
catalysis can be achieved by dense amorphous packing.
PMID- 26428151
TI - Development of crosslinked methylcellulose hydrogels for soft tissue augmentation
using an ammonium persulfate-ascorbic acid redox system.
AB - Hydrogels composed of methylcellulose are candidate materials for soft tissue
reconstruction. Although photocrosslinked methylcellulose hydrogels have shown
promise for such applications, gels crosslinked using reduction-oxidation (redox)
initiators may be more clinically viable. In this study, methylcellulose modified
with functional methacrylate groups was polymerized using an ammonium persulfate
(APS)-ascorbic acid (AA) redox initiation system to produce injectable hydrogels
with tunable properties. By varying macromer concentration from 2% to 4% (w/v),
the equilibrium moduli of the hydrogels ranged from 1.47 +/- 0.33 to 5.31 +/-
0.71 kPa, on par with human adipose tissue. Gelation time was found to conform to
the ISO standard for injectable materials. Cellulase treatment resulted in
complete degradation of the hydrogels within 24h, providing a reversible
corrective feature. Co-culture with human dermal fibroblasts confirmed the
cytocompatibility of the gels based on DNA measurements and Live/Dead imaging.
Taken together, this evidence indicates that APS-AA redox-polymerized
methylcellulose hydrogels possess properties beneficial for use as soft tissue
fillers.
PMID- 26428152
TI - Insights into the nucleation role of cellulose crystals during crystallization of
poly(beta-hydroxybutyrate).
AB - Cellulose crystals, including microcrystalline cellulose (MCC) and
nanocrystalline cellulose (NCC), were used as the fillers to prepare green
composites with poly(beta-hydroxybutyrate) (PHB) by melt mixing for
crystallization study. The results reveal that the spherulite morphology of PHB
and its composites depends highly on the crystallization temperature, evolving
from bundle shaped to ring-banded and finally to irregular or zigzag textures
with increase of temperature. However, the ring-banded structure is strongly
affected by the presence of cellulose crystals, and the average band space
decreases evidently with the addition of MCC or NCC. Compared with PHB/MCC
composite, PHB/NCC composite shows degraded spherulite structure with smaller
band space and higher flocculation level of peak-to-valley height because of
stronger unbalanced stresses in this system. Besides, cellulose crystals can act
as good heterogeneous nucleating agent to accelerate the crystallization of PHB,
which is further confirmed by the polarized optical microscopy observations and
the kinetic analyses.
PMID- 26428153
TI - Influence of tiopronin, captopril and levamisole therapeutics on the oxidative
degradation of hyaluronan.
AB - The ability to protect hyaluronic acid (HA) from oxidative degradation by cupric
ions and ascorbate (production of (*)OH and peroxy-type radicals) during acute
phase joint inflammation has been investigated using the following drugs:
tiopronin, captopril, and levamisole. Radical scavenging activity, i.e. the
propensity for donation of electrons was assessed for the drugs by ABTS and DPPH
assays. The kinetics of HA degradation have been measured in the presence of each
drug using rotational viscometry. The results of ABTS and DPPH assays show the
highest radical scavenging activity for captopril, followed by tiopronin. For
levamisole, no effect was observed. Captopril and tiopronin prevented HA
degradation induced by (*)OH radicals in a similar manner, while tiopronin was
more effective in scavenging peroxy-type radicals. On the other hand, levamisole
was shown to be a pro-oxidant. Recovered HA fragments were characterized using FT
IR analysis, the incorporation of a sulphur atom from captopril and tiopronin but
not from levamisole into the HA molecule was demonstrated.
PMID- 26428154
TI - Complexation of pectin with macro- and microelements. Antianemic activity of Na,
Fe and Na, Ca, Fe complexes.
AB - New water-soluble pectin complexes with Ca(2+), Mg(2+), Co(2+), Cu(2+), Fe(2+),
Mn(2+), Zn(2+) on the basis of pectin biopolymer have been synthesized and
successfully tested on white rats. For a starting, we have obtained a sodium
pectate to enhance solubility of target complexes as a whole. Shortly afterwards,
running the reaction of ligand exchange of Na(+) ions with corresponding s-, d-
metal cations we were able to synthesize new pectin complexes. The ranges of s-,
d-metals salts concentrations were detected experimentally, in which the
selective formation of water-soluble complexes occurred. Antianemic effect of new
pectin complexes with Na, Fe and Na, Ca, Fe was investigated on white rats with
posthemorrhagic anemia. Under the effect of complexes, the improvement of animals
and prevention of erythropoiesis disorders were observed. Antianemic effect of
the complexes manifested itself in the doses equivalent to 25% or 50% of the iron
daily rate, recommended in the treatment of iron-deficiency anemia with the drugs
based on iron sulphate.
PMID- 26428155
TI - Isolation and characterization of cellulose nanocrystals from parenchyma and
vascular bundle of oil palm trunk (Elaeis guineensis).
AB - In this study cellulose nanocrystals were isolated through acid hydrolysis
process from parenchyma and vascular bundle of oil palm trunk (Elaeis
guineensis). The morphological properties of obtained cellulose nanocrystals were
studied by scanning electron microscopy (SEM) and transmission electron
microscopy (TEM). The microscopy images showed smoother and cleaner surface of
parenchyma cellulose nanocrystals when compared to vascular bundle cellulose
nanocrystals. The TEM image shows a higher length and diameter for parenchyma
cellulose nanocrystals compared to vascular bundle cellulose nanocrystals. The
Fourier transform infrared (FTIR) spectra showed changes in functional groups
after acid hydrolysis due to removal of lignin, hemicelluloses and other
impurities in both type of cellulose nanocrystals. Crystallinity index of
cellulose nanocrystals was observed higher for vascular bundle as compared to
parenchyma. Thermogravimetric analysis (TGA) was performed to study the thermal
stability of cellulose nanocrystals and it was observed higher for parenchyma
cellulose nanocrystals compared to vascular bundle.
PMID- 26428156
TI - Macro-hydrogels versus nanoparticles by the controlled assembly of
polysaccharides.
AB - The controlled assembly of oppositely charged chitosan (CS, Mw ~ 33 * 10(3) to
600 * 10(3)g mol(-1)) and dextran sulfate (DS, Mw = 1.3 * 10(6)g mol(-1)) or
heparin (HP, Mw = 1.8 * 10(4)g mol(-1)) led either to nanoparticles or macro
hydrogels, at room temperature. The control over the electrostatic attractive
interactions was achieved using 2 mol L(-1) NaCl in the polyion solutions and
subsequent dialysis to let the assembly occur. Macrohydrogels formed with an
excess of polyanion. In the presence of an excess of polycation, colloidal gels
were exclusively obtained. At salt concentrations lower than 1 mol L(-1), the
spontaneous gelation provided macro-hydrogels, whatever the polyion in excess.
Rheology measurements showed a similar elastic behaviour for CS-DS and CS-HP
hydrogels, though CS-HP hydrogels appeared less cohesive. SAXS experiments
revealed an aggregate morphology with internal and surface structure depending on
the degree of acetylation (DA) of chitosan.
PMID- 26428157
TI - Inclusion complex of erlotinib with sulfobutyl ether-beta-cyclodextrin:
Preparation, characterization, in silico, in vitro and in vivo evaluation.
AB - The aim of the study was to investigate the impact of erlotinib sulfobutyl ether
beta-cyclodextrin complex (ERL-SBE-beta-CD) on ERL dissolution rate and oral
bioavailability. Preliminary comparative phase solubility study indicated ERL
exhibited maximum solubility in SBE-beta-CD solution. Optimal experimental design
confirmed freeze drying of SBE-beta-CD:ERL in 1:1.05 molar ratio as the optimum
method. Differential scanning calorimetry (DSC), Fourier transformation infrared
spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), proton nuclear magnetic
resonance ((1)H NMR) and two-dimensional rotating-frame Overhauser effect
spectroscopy (2D ROESY NMR) confirmed the inclusion complexation. The in silico
computational study, employed to analyze the comparative interactions of ERL with
SBE-beta-CD and beta-CD, indicated ease of ERL-SBE-beta-CD complexation. In vitro
dissolution and in vivo bioavailability studies further confirmed the ERL-SBE
beta-CD as a valuable approach to enhance ERL oral bioavailability with 3.6-fold
increase in relative oral bioavailability with higher Cmax (134.29 +/- 36.51 vs.
42.36 +/- 1.75 MUg/ml) and AUC0-infinity (2103.47 +/- 156.75 vs.580.43 +/- 71.91
MUg/ml h) over the free drug. The complex exhibited 3.2-fold increase in Cmax
with 5.4-fold decrease in Tmax (0.5 +/- 0.2 vs. 2.7 +/- 0.8h) in comparison to
pure ERL. Thus, ERL-SBE-beta-CD complexation exhibits a potential to enhance oral
bioavailability of ERL leading to reduce dose and dose-related side effects.
PMID- 26428158
TI - Functional chondroitin sulfate from Enteroctopus dofleini containing a 3-O-sulfo
glucuronic acid residue.
AB - There are several reports that chondroitin sulfate containing K-type units [GlcA
(3S)-GalNAc (4S)] exhibiting similar levels of neurite outgrowth promoting
activities as CS having high amounts of B-, D- and E-type disulfated
disaccharides. Although CS containing K-type units possess important biological
activities, there are only few sources, such as king crab cartilage, squid
cartilage or sea cucumber. In this study, CS containing 13.9% of K-type units was
found in octopus (Enteroctopus dofleini) cartilage using different substrate
specificities of chondroitinases. The 2D NMR spectra showed cross-peaks assigned
to protons on sugar ring of GlcA (3S), demonstrating the presence of K-type units
in octopus CS. Furthermore, proportion of fucosylated disaccharide units in
octopus CS was very low. Octopus CS showed high affinity for growth factors and
stimulated neurite outgrowth of hippocampal neurons, similar to the activity of
squid CS-E. These results strongly suggest that octopus cartilage is a rich
source of CS-K and has important biological activities.
PMID- 26428159
TI - Hydrodynamic behavior and dilute solution properties of Ulva fasciata algae
polysaccharide.
AB - Hydrodynamic behavior and dilute solution properties of Ulva fasciata
polysaccharides (UFP) were investigated. Experimental results indicated that the
variation of hydrodynamic behavior of UFP was affected by the type and
concentration of salts. The specific viscosity of UFP in water increased with its
increasing concentration. The slopes of the double logarithmic plots in the
dilute and semi-dilute solutions were 0.86 and 1.99, respectively. The molecular
conformation could be semi-flexible like. Huggins plots of UFP solutions in the
presence of salts including Na(+), K(+), Mg(2+) and Ca(2+) showed that the
hydrodynamic behavior of the UFP was strongly affected by the types and strength
of salt ion. The stiffness parameter of UFP solution was 0.1149, higher than that
of other reported polysaccharides, indicating that it could tolerate high salt
concentration. Dynamic rheological results suggested that 0.5% UFP solution was a
typical characteristic of polymer solution in the dilute region. This work
provided some valuable and fundamental information in understanding the
physicochemical properties of UFP solution.
PMID- 26428160
TI - Pinhao starch and coat extract as new natural cosmetic ingredients: Topical
formulation stability and sensory analysis.
AB - The objective of this study was to use pinhao derivatives, starch and coat
extract, as new natural ingredients to develop cosmetic formulations. Two types
of formulation, gel and emulgel, and their controls were developed. The
formulations were characterized by stability studies using thermal stress. The
parameters analyzed were resistance to centrifugation, pH, spreadability,
rheology, content of phenolic compounds and antioxidant activity. Sensory
analysis was also performed to verify the acceptability of the ingredients to
potential consumers. The pH was kept the same after heating/freezing cycles for
all formulations, and the formulations showed stability by resistance to
centrifugation. The formulations did not induce any skin irritation or cutaneous
pH alteration. The pinhao starch addition improved spreadability stability and
increased viscosity when compared with control formulations. The pinhao coat
extract used in these formulations is a good source of phenolic compounds and
antioxidant activity. Moreover, sensory analysis indicates that the emulgel
formulation is the best vehicle for adding pinhao starch and pinhao coat extract.
PMID- 26428161
TI - Chemical isolation and characterization of different cellulose nanofibers from
cotton stalks.
AB - Recently, cellulose nanofibers (CNFs) have received wide attention in green
nanomaterial technologies. Production of CNFs from agricultural residues has many
economic and environmental advantages. In this study, four different CNFs were
prepared from cotton stalks by different chemical treatments followed by
ultrasonication. CNFs were prepared from untreated bleached pulp, sulfuric acid
hydrolysis, and TEMPO [(2,2,6,6-tetramethylpiperidin-1-yl) oxy radical]-mediated
oxidation process. Physical and chemical properties of the prepared CNFs such as
morphological (FE-SEM, AFM), structural (FTIR), and thermal gravimetric analysis
(TGA) were investigated. Characterization results clearly showed that the method
of preparation results in a significant difference in the structure, thermal
stability, shape and dimensions of the produced CNFs. TEMPO-mediated oxidation
produced brighter and higher yields (>90%) of CNFs compared to other methods. FE
SEM and AFM analysis clearly indicated that, TEMPO-mediated oxidation produced
uniform nano-sized fibers with a very small diameter (3-15 nm width) and very
small length (10-100 nm). This was the first time uniform and very small
nanofibers were produced.
PMID- 26428162
TI - Review on complement analysis method and the roles of glycosaminoglycans in the
complement system.
AB - Complement system is composed of over 30 proteins and it plays important roles in
self-defence and inflammation. There are three activation pathways, including
classical pathway, alternative pathway and lectin pathway, in complement system,
and they are associated with many diseases such as osteoarthritis and age-related
macular degeneration. Modulation of the complement system may be a promising
strategy in the treatment of related diseases. Glycosaminoglycans are anionic
linear polysaccharides without branches. They are one kind of multi-functional
macromolecules which have great potential in regulating complement system. This
review is organized around two aspects between the introduction of complement
system and the interaction of glycosaminoglycans with complement system. Three
complement activation pathways and the biological significance were introduced
first. Then functional analysis methods were compared to provide a strategy for
potential glycosaminoglycans screen. Finally, the roles of glycosaminoglycans
played in the complement system were summed up.
PMID- 26428163
TI - Preparation of alginate-chitosan fibers with potential biomedical applications.
AB - The preparation of alginate-chitosan fibers, through wet spinning technique, as
well as the study of their properties as a function of chitosan's molecular
weight and retention time in the coagulation bath, is presented and discussed in
this work. Scanning electron microscopy (SEM) revealed that the fibers presented
irregular and rough surfaces, with a grooved and heavily striated morphology
distributed throughout the structure. Dynamic mechanical analysis (DMA) showed
that, with the exception of elongation at break, the incorporation of chitosan
into the fibers improved their tensile properties. The in vitro release profile
of sulfathiazole as a function of chitosan's molecular weight indicated that the
fibers are viable carriers of drugs. Kinetic models showed that the release of
the model drug is first-order, and the release mechanism is governed by the
Korsmeyer-Peppas model. Likewise, fibers loaded with sulfathiazole showed
excellent inhibition of Escherichia coli growth after an incubation time of 24h
at 37 degrees C.
PMID- 26428164
TI - Ionic liquid-mediated technology to produce cellulose nanocrystals directly from
wood.
AB - We report for the first time the direct extraction of cellulose nanocrystals
(CNCs) from wood by means of a 1-ethyl-3-methylimidazolium acetate ([EMIM][OAc])
treatment. A native cellulosic product could be recovered in 44% yield with
respect to wood cellulose content. The product was analyzed for morphological
(TEM, AFM, XRD), chemical (FTIR, (13)C CP/MAS NMR), thermal (DSC, TGA) and
surface properties (Zeta potential, contact angle). These analyses evidenced the
presence of partially acetylated (surface DS=0.28) nanocrystals of native
cellulose I microstructure, with a crystallinity index of about 75% and aspect
ratio of 65. Direct production of CNCs from wood is ascribed to the simultaneous
capability of [EMIM][OAc] to (1) dissolve lignin in situ while only swelling
cellulose, (2) decrease intermolecular cohesion in wood via acetylation, and (3)
to catalyze cellulose hydrolysis.
PMID- 26428165
TI - Internal structure and thermo-viscoelastic properties of agar ionogels.
AB - Ionic liquids (IL) can alter the physical properties of agar hydrogels. Rheology
studies show that gels with wide range of storage moduli (gel strength) G0 values
ranging from 1 to 20 KPa could be made in imidazolium based IL solutions where
the IL concentration may not exceed 5% (w/v). Gelation and gel melting
temperatures (tgel and Tm) could be altered by as much as ~ 10 degrees C. Small
angle neutron scattering studies revealed the presence of fibre bundles of agar
double helices having typical length of 120 nm that increased to ~ 180 nm under
favorable conditions. These structures gain flexibility from the cladding of the
agar bundles by IL molecules which in turn caused partial charge neutralization
of its surface. Raman spectroscopy revealed differential hydration of these
bundles. It was found that IL molecules with longer alkyl chain (more
hydrophobic) altered the gel homogeneity, and changed its thermal and mechanical
properties significantly. Therefore, customization of agar hydrogels in green
solvent medium (IL solutions) widens the scope of its application potential that
may include sensing.
PMID- 26428166
TI - Optimization of fermentation conditions of pectin production from Aspergillus
terreus and its partial characterization.
AB - Figures of persimmons for the world's top ten persimmon producing countries are
about 4000,000 tons in 2011 and are increasing every year according to FAO
statistics. However, there is not any report on pectin production by microbial
with persimmon peel as the source. Optimization of fermentation conditions of
pectin production from Aspergillus terreus in submerged culture and partial
characterization of pectin were carried out in the work. An optimum fermentation
condition for pectin production was obtained through a central composite
rotatable design in response surface methodology as follows: fermentation time,
30.09 h, temperature, 25.00 degrees C and the initial pH in the fermentation
medium, 6.90, respectively and the pectin yield reached the maximal value 0.449
g/g. Persimmon peel pectin had highly methoxylated (62.51%), high galacturonic
acid content (82.28%) than citrus pectin, and was classified as the highly
methoxylated pectin, the results indicated that persimmon peel had potential good
resources for pectin production. The investigation can make it available to
utilize persimmon peel to produce high methoxyl pectin for food industry,
pharmacy and cosmetic manufacture.
PMID- 26428167
TI - Starch/silver nanocomposite: Effect of thermal treatment temperature on the
morphology, oxygen and water transport properties.
AB - The present work reports a strategy involving the preparation of nanostructured
starch based film containing silver nanoparticles (AgNPs) using a completely
green chemistry process. The nanocomposite films were prepared by solution cast
process. The AgNPs were in situ generated inside the polymer film by thermal
treatment at different temperatures (25, 40 and 85 degrees C). The influence of
the presence and the amount of reducing agent (glucose) were also investigated.
For all nanocomposite films, the AgNPs were spherical with a diameter less than
15 nm. Contrary to the presence of glucose, thermal treatment condition was a key
factor for the AgNPs structure. Crystalline AgNPs were obtained only after
thermal treatment at 85 degrees C. Improvements of water and oxygen barrier
properties near to one decade were observed in this last case and were explained
by the formation of crystalline AgNPs associated to the establishment of strong
interactions between AgNPs and starch polymer matrix.
PMID- 26428168
TI - Facile approach to synthesize chitosan based composite--Characterization and
cadmium(II) ion adsorption studies.
AB - In this present study, the physicochemical properties, nature and morphology of
prepared composite materials involving Activated Eskom fly ash (A-FA) and
biopolymer-chitosan (Ch) for two components composite materials were
investigated. The nature, morphology, elemental characterizations of these
materials were carried out by means of modern analytical methods such as scanning
electron microscopy (SEM), X-ray diffraction (XRD), X-ray fluorescence (XRF), UV
vis spectroscopy (UV-vis), and Fourier transform infrared spectroscopy (FTIR.
Other physicochemical characterizations undertaken were carbon, nitrogen and
hydrogen (CNH) analysis, and ash content. The precursors and composite materials
were then applied to the sorption of cadmium (Cd(2+)) from aqueous water. Maximum
Cd(2+) adsorption capacity (Qmax) was recorded to be 87.72 mg/g at pH 8. The
adsorption kinetics of the composite materials fitted well with the pseudo second
order kinetic model while the adsorption isotherm data could be well described by
the Langmuir isotherm model.
PMID- 26428169
TI - Delivery of liquorice extract by liposomes and hyalurosomes to protect the skin
against oxidative stress injuries.
AB - Liquorice extract, obtained by percolation in ethanol of Glycyrrhiza glabra L.
roots, was incorporated in liposomes and hyalurosomes, new phospholipid-sodium
hyaluronate vesicles, and their protective effect against oxidative stress skin
damages was probed. As a comparison, raw glycyrrhizin was also tested. All the
vesicles were small in size (<= 100 nm), with a highly negative zeta potential
ensuring long-term stability, and able to incorporate a high amount of the
extract. In vitro tests showed that the liquorice extract loaded in vesicles was
able to scavenge DPPH free radical (80% inhibition) and to protect 3T3
fibroblasts against H2O2-induced oxidative stress, restoring the normal
conditions. By contrast, glycyrrhizin showed poor antioxidant activity, and was
not able to efficiently counteract the oxidative effect of H2O2. In addition, the
incorporation of the liquorice extract into the vesicular systems promoted the
proliferation and migration of 3T3 fibroblasts, favouring the closure of the
scratched area. In vivo anti-inflammatory tests on mice confirmed the ability of
the proposed nanosystems to improve the local efficacy of the extract, favouring
the re-epitelization process.
PMID- 26428170
TI - Effect of the oxidation treatment on the production of cellulose nanofiber
suspensions from Posidonia oceanica: The rheological aspect.
AB - Different grades of cellulose nanofibrils (CNF) were prepared from Posidonia
oceanica balls and leaves (POB and POL). Pretreatment using 2,2,6,6
tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation was performed to
facilitate the fibrillation during ultrafine friction grinding process. The
ensuing CNF batches were compared in terms of morphology and degree of
fibrillation. The rheological properties of the produced CNF suspensions were
also analyzed for varying doses of sodium hypochlorite used during the TEMPO-
mediated oxidation procedure. The stronger fibrous network structures were formed
when increasing the oxidant concentration, which was confirmed by the increase of
the storage moduli value. P. oceanica balls were found to undergo stronger
fibrillation and, consequently, to form stronger networks, compared to P.
oceanica leaves, when using equivalent concentration of the oxidizing agent.
PMID- 26428171
TI - Development and characterization of a new hydrogel based on galactomannan and
kappa-carrageenan.
AB - A new hydrogel based on two natural polysaccharides was prepared in aqueous
medium with 1.7% (w/v) galactomannan (from Cassia grandis seeds) and different
concentrations of kappa-carrageenan (0.3, 0.4 and 0.5%w/v), CaCl2 (0.0, 0.1 and
0.2M) and pH (5.0, 5.5 and 6.0), using a full factorial design based on
rheological parameters. The best formulation was obtained with 1.7% (w/v)
galactomannan and 0.5% (w/v) kappa-carrageenan, containing 0.2M CaCl2 at pH 5.0.
Nuclear magnetic resonance and scanning electron microscopy where used in order
to characterize the hydrogel formulation. A shelf life study was carried out with
this formulation along 90 days-period of storage at 4 degrees C, evaluating pH,
color, microbial contamination and rheology. This hydrogel showed no significant
changes in pH, no microbial contamination and became more translucent along the
aging. Analyses by nuclear magnetic resonance and rheology showed a larger
organization of the polysaccharides in the hydrogel matrix. The results
demonstrated that this hydrogel was stable with possible applications in medical
and cosmetic fields.
PMID- 26428172
TI - Application of chitosan and its N-heterocyclic derivatives for preconcentration
of noble metal ions and their determination using atomic absorption spectrometry.
AB - Chitosan and its N-heterocyclic derivatives N-2-(2-pyridyl)ethylchitosan (2-PEC),
N-2-(4-pyridyl) ethylchitosan (4-PEC), and N-(5-methyl-4-imidazolyl)
methylchitosan (IMC) have been applied in group preconcentration of gold,
platinum, and palladium for subsequent determination by atomic absorption
spectroscopy (AAS) in solutions with high background concentrations of iron and
sodium ions. It has been shown that the sorption mechanism, which was elucidated
by XPS, significantly influences the sorption capacity of materials, the
efficiency of metal ions elution after preconcentration, and, as a result, the
accuracy of metal determination by AAS. We have shown that native chitosan was
not suitable for preconcentration of Au(III), if the elution step was used as a
part of the analysis scheme. The group preconcentration of Au(III), Pd(II), and
Pt(IV) with subsequent quantitative elution using 0.1M HCl/1M thiourea solution
was possible only on IMC and 4-PEC. Application of IMC for analysis of the
national standard quartz ore sample proved that gold could be accurately
determined after preconcentration/elution with the recovery above 80%.
PMID- 26428173
TI - Enhancing biocompatibility of some cation selective electrodes using heparin
modified bacterial cellulose.
AB - Bacterial cellulose (BC) and heparin-modified bacterial cellulose (HBC) were
utilized to enhance the biocompatibility of highly thrombogenic PVC-based
potassium and calcium membrane electrodes. Three types of membrane electrodes
were prepared: (1) conventional PVC electrode (control), (2) PVC-based electrode
sandwiched with bacterial cellulose membrane (BC-PVC), and (3) PVC-based
electrode sandwiched with heparin-modified bacterial cellulose membrane (HBC
PVC). The potentiometric response characteristics of the modified potassium and
calcium membrane electrodes (BC-PVC and HBC-PVC) were compared with those of the
control PVC-based potassium and calcium selective electrode, respectively.
Response characteristics of the modified membrane electrodes were comparable to
the control PVC membrane electrode. The platelet adhesion investigations
indicated that (BC) and (HBC) layers are less thrombogenic compared to PVC.
Therefore, use of BC or HBC would enable the enhancement of the biocompatibility
of PVC-based membrane electrodes for potassium and calcium while practically
maintaining the overall electrochemical performance of the PVC sensing film.
PMID- 26428174
TI - A curcumin activated carboxymethyl cellulose-montmorillonite clay nanocomposite
having enhanced curcumin release in aqueous media.
AB - A novel curcumin activated carboxymethylcellulose-montmorillonite nanocomposite
is reported. A superabsorbent biopolymer; carboxymethyl cellulose (CMC) was used
as an emulsifier for curcumin which is a turmeric derived water insoluble
polyphenolic compound with antibacterial/anti-cancer properties. Montmorillonite
(MMT) nanoclay was incorporated in the formulation as a matrix material which
also plays a role in release kinetics. It was observed that water solubility of
curcumin in the nanocomposite has significantly increased (60% release within 2h
and 30 min in distilled water at pH 5.4) compared to pure curcumin. The prepared
curcumin activated carboxymethylcellulose-montmorillonite nanocomposite is
suitable as a curcumin carrier having enhanced release and structural properties.
PMID- 26428175
TI - Xylan-degrading enzymes from Aspergillus terreus: Physicochemical features and
functional studies on hydrolysis of cellulose pulp.
AB - Two endo-beta-1,4-xylanases named XylT1 and XylT2, previously purified from
Aspergillus terreus, were structurally investigated by fluorescence quenching and
characterized with respect to their binding properties with phenolic compounds.
Neutral and charged quenchers had access to both enzymes in neutral and alkaline
pHs. The greatest access was noted for the negative quencher, possibly due to
positive amino acid residues in the vicinity of tryptophan. These tryptophan
environments may partially explain the conformational differences and lower
binding constants of phenolic compounds for XylT2 than XylT1Phenolic compounds
had lower binding constants for XylT2 than XylT1. These results show that
xylanases present structural and functional differences, despite belonging to
similar families. XylT1 and XylT2 were also evaluated for their ability to
hydrolyze cellulose pulp in different stages of bleaching. Both enzymes promoted
hydrolysis of cellulose pulps, which was confirmed by the release of total
reducing sugars, pentoses and chromophoric material. Analysis of released
xylooligosaccharides demonstrated a preferential release of xylobiose. None of
xylanases released glucose, showing that they do not hydrolyze the cellulose
present in the pulp, making both enzymes excellent choices for bio-bleaching
applications.
PMID- 26428176
TI - Carbohydrate base co-polymers as an efficient immobilization matrix to enhance
lipase activity for potential biocatalytic applications.
AB - In the present study, we have synthesized biocompatible hybrid blend of
cellulosic polymers of hydroxypropyl-methyl-cellulose (HPMC) and chitosan (CHY)
for the immobilization of Candida rugosa lipase (CRL). The immobilized
biocatalyst HPMC:CHY:CRL was subjected for characterization such as SEM, TGA,
water content analysis, lipase activity, specific activity and protein content
analysis. The kinetic parameter study (Rmax/Km) demonstrated improved
biocatalytic activity of lipase after immobilization on carbohydrate co-polymers
of HPMC:CHY. This biocatalyst was then employed to study practical biocatalytic
applications for kinetic resolution which provided 50% conversion and >94%
enantiomeric excess of substrate/product (ees/eep). The protocol demonstrated
excellent recyclability upto five cycles. Finally, we studied influence of
immobilization on cellulosic polymers for substrate, structure and reactivity for
kinetic resolution. Hence, we investigated R0 (initial reaction rate), E-value
(enantioselectivity) and Ea (activation energy). This study confirms that, lipase
immobilized on carbohydrate polymers had 3-4 folds higher biocatalytic activity
as compared to crude CRL.
PMID- 26428177
TI - Effect of sub- and supercritical water treatments on the physicochemical
properties of crab shell chitin and its enzymatic degradation.
AB - This study examined the effects of sub- and supercritical water pretreatments on
the physicochemical properties of crab shell alpha-chitin and its enzymatic
degradation to obtain N,N'-diacetylchitobiose (GlcNAc)2. Following sub- and
supercritical water pretreatments, the protein in the crab shell was removed and
the residue of crab shell contained alpha-chitin and CaCO3. Prolonged
pretreatment led to alpha-chitin decomposition. The reaction of pure alpha-chitin
in sub- and supercritical water pretreatments was investigated separately; we
observed lower mean molecular weight and weaker hydrogen bonds compared with
untreated alpha-chitin. (GlcNAc)2 yields from enzymatic degradation of
subcritical (350 degrees C, 7 min) and supercritical water (400 degrees C, 2.5
min) pretreated crab shell were 8% and 6%, compared with 0% without any
pretreatment. This study shows that sub- and supercritical water pretreatments of
crab shell provide to an alternative method to the use of acid and base for
decalcification and deproteinization of crab shell required for (GlcNAc)2
production.
PMID- 26428178
TI - Functional, thermal, and antimicrobial properties of soluble soybean
polysaccharide biocomposites reinforced by nano TiO2.
AB - This study describes a new polysaccharide-based bionanocomposite developed
through solvent casting. Different concentrations (i.e., 0%, 1%, 3%, and 5%
(w/w)) of nano titanium dioxide (TiO2-N) were incorporated into soluble soybean
polysaccharide (SSPS), and the functional properties of the resultant SSPS films
were estimated. Incorporation of TiO2-N into the SSPS matrix decreased water
vapor permeability from 7.41 to 4.44 * (10(-11)gm(-1) s(-1) Pa(-1)) and oxygen
permeability from 202 to 98 (cm(3)MUmm(-2) d(-1) atm(-1)). Moisture content also
decreased, the glass transition temperature increased, and the mechanical
properties and heat seal strength of the SSPS films improved. SSPS
bionanocomposite films showed excellent antimicrobial activity against
Escherichia coli and Staphylococcus aureus. In summary, TiO2-N shows potential
use as a filler in SSPS-based films for the food and non-food industries.
PMID- 26428179
TI - Synthesis and applications of eco-magnetic nano-hydroxyapatite chitosan composite
for enhanced fluoride sorption.
AB - Adsorption is a significant reaction occurs between adsorbent/water interface for
controlling the pollutants in the aqueous environment. In this regard, an eco
magnetic biosorbent was prepared by uniform deposition of magnetic Fe3O4
particles on the surface of nano-hydroxyapatite (n-HAp)/chitosan (CS)
nanocomposite namely Fe3O4@n-HApCS composite as versatile sorbent for fluoride
sorption. The resulting Fe3O4@n-HApCS nanocomposite was characterized by FTIR and
SEM with EDAX techniques. The defluoridation capacity (DC) was found to depend on
the contact time, pH, co-existing anions, initial fluoride concentration and
temperature. The sorption isotherm was investigated by Freundlich, Langmuir and
Temkin isotherm models using the batch method. The thermodynamic parameters
revealed the feasibility, spontaneity and endothermic nature of fluoride
sorption. The results of this research work designated that Fe3O4@n-HApCS
composite having the excellent defluoridation capacity than the individual
components and interesting to note that the easy magnetic separation of Fe3O4@n
HApCS composite from aqueous medium.
PMID- 26428180
TI - Cellulosimicrobium cellulans strain E4-5 enzymatic hydrolysis of curdlan for
production of (1 -> 3)-linked beta-D-glucan oligosaccharides.
AB - In order to find an efficient enzymatic tool for curdlan degradation to produce
(1 -> 3)-linked beta-D-glucan oligosaccharides, strain E4-5 (registration number
JN089883, Genbank) was isolated from seaside soil. The 16S rRNA gene sequencing
classified it as Cellulosimicrobium cellulans. It was the first reported
microorganism that succeeded in degrading high-set heated curdlan blocks. The
ferments of strain E4-5 also showed good degradation effects on laminaran and
alkali-neutralized curdlan. Due to the products with less amount of glucose, it
was assumed that endo-1,3-beta-glucanases of strain E4-5 had a greater
hydrolyzing effect than exo-1,3-beta-glucanases. This indicated that strain E4-5
was a promising microorganism to hydrolyze (1 -> 3)-linked beta-D-glucan.
Moreover, alkali-neutralization pretreatment was effective for promoting a more
diversified degree of polymerization (DP) of (1 -> 3)-linked beta-D-glucan
oligosaccharides under enzymatic hydrolysis and will pave the way for making full
use of curdlan for production of glucan oligosaccharides.
PMID- 26428181
TI - Preparation and characterization of novel bionanocomposite based on soluble
soybean polysaccharide and halloysite nanoclay.
AB - In this research, casting method was used to prepare novel polysaccharide-based
bio-nanocomposite films with halloysite nanoclay (HNC). HNC was incorporated into
soluble soybean polysaccharide (SSPS) at different concentrations (e.g., 1, 3,
and 5%, w/w). Functional properties of SSPS films were evaluated following by
ASTM standards. Incorporating HNC to SSPS matrix decreased water vapor
permeability from 7.41 * 10(-11) to 3.27 * 10(-11) (gm(-1) s(-1) Pa(-1)) and
oxygen permeability from 202 to 84 cm(3)(MUm m(-2) day(-1) atm(-1)). By addition
of HNC to SSPS films, glass transition temperature, tensile strength, and heat
seal strength was increased and elongation at break was decreased. Uniform and
smooth surface morphology revealed by scanning electron microscopy and shows no
sign of phase separation among the film constitutes. In summary, HNC has the
potential to be a filler in SSPS-based films for use in food and non-food
packaging industries.
PMID- 26428182
TI - Structural characterization and antioxidant activity of a novel
heteropolysaccharide from the submerged fermentation mycelia of Ganoderma
capense.
AB - A novel heteropolysaccharide (GCPB-2) with a molecular mass of 1.03*10(5)Da was
isolated from the submerged fermentation culturing mycelia powder of Lingzhi,
Ganoderma capense, by DEAE-52 cellulose, DEAE Sepharose CL-6B, and Sephadex G-75
column chromatography. Its chemical structure was characterized for the first
time. The antioxidant activity was evaluated by two antioxidant assay methods.
The result of this study introduced G. capense as a possible valuable source that
helped to exhibit some antioxidant properties. The homogeneous polysaccharide was
composed of xylose and arabinose in the molar ratio of 1:1, and showed a specific
optical rotation of [alpha]D(25)=+161 degrees (c 1.0, H2O). Monosaccharide
analysis, partial acid hydrolysis, periodic acid oxidation, methylation analysis,
gas chromatography-mass spectrometry (GC-MS), Fourier transform-infrared
spectroscopy (FT-IR), and nuclear magnetic resonance (NMR) spectroscopy ((1)H,
(13)C, HMQC and HMBC) were conducted to elucidate its structure. The backbone of
GCPB-2 was composed of (1 -> 4)-linked-beta-D-xylopyranose residues which
branched at O-3. The two branches consisted of (1 -> 3)-linked-beta-L
arabinopyranose terminated with beta-D-xylopyranose residues, and (1 -> 4)-linked
beta-L-arabinopyranose terminated with beta-D-arabinopyranose residues. In the in
vitro antioxidant assay, GCPB-2 was found to possess 1-diphenyl-2-picryl-hydrazyl
(DPPH) radical-scavenging activity with an EC50 value of 0.379 MUM. The findings
of this study indicated that GCPB-2 possesses the hydroxyl radical-scavenging
activity, which provided an experimental evidence to support the G. capense as
functional foods in some Asian countries. To understand better the bioactivity of
GCPB-2, the antioxidant activity should be further investigated to find out its
mechanism in future work.
PMID- 26428183
TI - Biodegradation of cellulosic and lignocellulosic waste by Pseudoxanthomonas sp R
28.
AB - A microbial consortium, designated Con R, was established by successive sub
cultivation which can degrade 83% of filter paper after 15 days of incubation
over control. Among the 14 bacterial isolates obtained from Con R, only bacterial
isolate (R-28) was capable of degrading filter paper. Based on 16S rRNA gene
sequence, R-28 was identified as Pseudoxanthomonas sp R-28. After 5 days of
incubation, degradation efficiencies of Pseudoxanthomonas sp R-28 on filter paper
and pure cellulosic waste were 96% and 95% respectively as compared to control.
Pseudoxanthomonas sp R-28 also degraded 60% of non-pretreated rice straw after 7
days as compared to control. The degradation kinetics through a modified logistic
model showed high correlation coefficient (R(2)) of 0.965 and 0.665 for
cellulosic and rice straw waste degradation respectively. Micro scale structural
analysis showed the development of fissures and gaps over time which further
supported the degradation potential of Pseudoxanthomonas sp R-28.
PMID- 26428184
TI - Gelling process for sodium alginate: New technical approach by using calcium rich
micro-spheres.
AB - Alginate based materials have become an important class of products in many
fields from the pharmaceutical industry to tissue engineering, because of their
ability to create stimuli responsive hydrogels. We present a new technical
approach for obtaining a controlled gelling process, based on the quantities of
Ca(2+) rich alginate micro-beads added as crosslinkers. The gels have been
evaluated in light of the amount of Ca(2+) added to the alginate solution, and in
light of the different dimensions of the micro-beads, using rheological
measurements to assess the variation in the storage modulus (G'), loss modulus
(G'') and complex viscosity (eta(*)) as well as swelling and deswelling tests.
The methodology was developed to obtain a material with specific characteristics
for application in the field of conservation. The material had to be able to
create a stable gel after being applied on the artwork surface and to confine the
solvent action at the interface during cleaning operations.
PMID- 26428185
TI - Tuning Fe3O4 nanoparticle dispersion through pH in PVA/guar gum/electrospun
membranes.
AB - Polyvinyl Alcohol (PVA)/guar gum (GG) membranes with different loads of
paramagnetic iron oxide Fe3O4 nanoparticles were successfully electrospun using
both non-alkaline and alkaline stock solutions. The nanoparticle homogeneity
distribution was clearly enhanced in fibers obtained from alkaline stock
solutions. This is mainly due to the interaction between GG and the metallic ion,
which also leads to further dispersion of remained uncoated nanoparticles in the
mixture. It was also noticed that GG favors nanoparticle stability in the mixture
and contributes to nanoparticle encapsulation. X-ray results showed that all
membranes were semi-crystalline. FTIR-ATR spectra showed that Fe-O absorption
band intensity improved with increasing nanoparticle load, reaching saturation at
3.5mg/ml Fe3O4 concentration under alkaline conditions. VSM analyses showed that
the nanoparticles are paramagnetic and were successfully incorporated by the
fibers. In vitro biocompatibility tests using L929 cells indicates adequate
levels of cytotoxicity and cell adhesion/proliferation assays for both membranes
obtained from non-alkaline and alkaline stock solutions. Therefore, they have
potential for biomedical applications as biodegradable wound dressing.
PMID- 26428186
TI - Starch based polyurethanes: A critical review updating recent literature.
AB - Recent advancements in material science and technology made it obvious that use
of renewable feed stock is the need of hour. Polymer industry steadily moved to
get rid of its dependence on non-renewable resources. Starch, the second largest
occurring biomass (renewable) on this planet provides a cheap and eco-friendly
way to form huge variety of materials on blending with other biodegradable
polymers. Specific structural versatility design for individual application and
tailor-made properties have established the polyurethane (PU) as an important and
popular class of synthetic biodegradable polymers. Blending of starch with
polyurethane is relatively a developing area in PU chemistry but with lot of
attraction for researchers. Herein, various starch based polyurethane materials
including blends, grafts, copolymers, composites and nano-composites, as well as
the prospects and latest developments are discussed. Additionally, an overview of
starch based polymeric materials, including their potential applications are
presented.
PMID- 26428187
TI - Fabrication and in vitro biological activity of betaTCP-Chitosan-Fucoidan
composite for bone tissue engineering.
AB - We developed tricalcium phosphate-chitosan-fucoidan biocomposite scaffold (TCP-Ch
Fu) by using the freeze-drying technique. The fabricated biocomposite scaffolds
were analyzed by spectroscopy and porosity measurement. The biomechanical
properties of scaffolds were assessed by compression test and the results
suggested that the incorporation of Fucoidan into the biocomposite improves the
compression strength of scaffolds. Biomineralization of scaffolds was evaluated
by soaking them in simulated body fluid and the results revealed that the
addition of Fucoidan into the scaffolds enhanced the formation of apatite layer
on the surface of biocomposite after 7 days of immersion. Alamar Blue assay
confirmed that the cell viability of human-derived bone marrow stromal cell was
superior in the TCP-Ch-Fuscaffold. The addition of Fucoidan to TCP-Ch increased
the release of osteocalcin, confirming that it can support osteogenic
differentiation of human mesenchymal stromal cells in in vitro culture. Thus, TCP
Ch-Fu could be a potential candidate for bone-tissue engineering applications.
PMID- 26428188
TI - Identification of a highly sulfated fucoidan from sea cucumber Pearsonothuria
graeffei with well-repeated tetrasaccharides units.
AB - Sea cucumber fucoidan is a major bioactive component of sea cucumber. The
structures of fucoidans have significant influences on their biological
activities. The present study clarified the delicate structure of a fucoidan from
Pearsonothuria graeffei. Fucoidan was obtained after papain digestion and
purified by ion chromatography. The carbohydrate sequence of fucoidan was firstly
determined by negative-ion electrospray tandem mass spectrometry (ES-MS) with
collision-induced dissociation of the oligosaccharide fragments, which were
obtained by mild acid hydrolysis, and completed by NMR for assignment of the
anomeric conformation. It was unambiguously identified as a tetrasaccharide
repeating unit with a backbone of [ -> 3Fuc (2S, 4S) alpha1 -> 3Fucalpha1-> 3Fuc
(4S) alpha1 -> 3Fuc#7 * 10#]n. The glycosidic bonds between the non-sulfated and
2,4-O-disulfated fucose residues were selectively cleaved, and highly ordered
oligosaccharide fragments with a tetrasaccharide repeating unit were obtained.
The highly 4-O- and 2, 4-di-O-sulfated polysaccharide deserves further
developments for Pharmacia use.
PMID- 26428189
TI - Timing of Gonadectomy in Patients with Complete Androgen Insensitivity Syndrome
Current Recommendations and Future Directions.
AB - This review highlights the controversy regarding timing of gonadectomy in
patients with complete androgen insensitivity syndrome (CAIS). We will review the
published literature regarding frequency of gonadal malignancy and summarize
historical findings. Recent research suggests that gonadectomy may be deferred
until adulthood due to the low risk of malignancy. An algorithm is also provided
to help guide clinicians in management of patients with complete androgen
insensitivity syndrome who have deferred gonadectomy.
PMID- 26428190
TI - Factors That Affect Perinatal Outcomes of the Second Pregnancy of Adolescents.
AB - STUDY OBJECTIVE: We assessed factors that might affect perinatal outcomes in
second pregnancies in adolescents. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS,
MAIN OUTCOME MEASURES: This longitudinal retrospective study was carried out on
66 adolescents who experienced 2 deliveries during their adolescence. Data were
collected for the first and second pregnancies. Odds ratios (ORs) and 95%
confidence intervals (CIs) for adverse perinatal outcomes in the second pregnancy
were calculated using a logistic regression model and SPSS software (version 17.0
for Windows; SPSS Inc, Chicago, IL). A P value < .05 was considered to indicate
statistical significance. RESULTS: Body mass index, number of antenatal care
visits, weight gain during pregnancy, incidence of anemia, smoking status,
gestational week at delivery, cesarean section rate, and birth weight were
similar between the first and second pregnancies of these adolescents. Neonatal
intensive care unit admission rate, preeclampsia rate, low neonatal birth weight
rate, and 5-minute Apgar scores <7 were significantly higher in the first than in
the second pregnancy (P < .001). Age of 16 years or younger at the time of first
pregnancy (OR = 1.5; 95% CI, 0.9-2.1; P < .01), less than an 18-month interval
between births (OR = 1.4; 95% CI, 0.2-1.7; P < .04), presence of gestational
complications in the first pregnancy (OR = 1.9; 95% CI, 1.0-3.4; P < .01), and
the presence of perinatal complications in the first pregnancy (OR = 1.3; 95% CI,
1.0-1.9; P < .01) were found to be significant indicators for adverse neonatal
outcomes in second pregnancies of adolescents. CONCLUSION: We found that the
second pregnancies of adolescents were associated with fewer adverse perinatal
outcomes than were their first pregnancies. However, some factors regarding the
presence of perinatal complications in the first pregnancy, such as maternal age
of 16 years or younger at the time of the first pregnancy and interval between
first and second pregnancy of less than 18 months, were found to increase the
risk of adverse perinatal outcomes for the second births.
PMID- 26428191
TI - Vaginal cones or balls to improve pelvic floor muscle performance and urinary
continence in women post partum: A quantitative systematic review.
AB - OBJECTIVES: the vaginal use of cones or balls aims to increase muscle performance
and thereby prevent or treat urinary incontinence. To date, no systematic review
has focused on the effectiveness of these devices specifically during the
postpartum period. The objectives of this review were: to compare the
effectiveness of vaginal cones or balls for improvement of pelvic floor muscle
performance and urinary continence in the postpartum period to no treatment,
placebo, sham treatment or active controls; to gather information on effect on
perineal descent or pelvic organ prolapse, adverse effects and economical
aspects. DESIGN: quantitative systematic review. DATA SOURCES: 14 scientific
databases (including PubMed and CINAHL) and the world-wide web; experts were
contacted for published and unpublished data. REVIEW METHODS: studies had to be
randomised/quasi-randomised trials and have female participants up to one year
after childbirth. The intervention is compared to no treatment, placebo, sham
treatment or active controls. Outcome measures relate to pelvic floor muscle
performance or urinary incontinence. Studies were selected, 'risk of bias'
assessed, and data extracted by two reviewers independently with inter-reviewer
agreement. MAIN FINDINGS: one study met the inclusion criteria; its original data
were re-analysed. In an intention-to-treat analysis, compared with the control
group, the cone group showed a statistically significant lower rate of urinary
incontinence; compared with the exercise group, the prevalence was similar.
However, the validity of the analysis is limited. CONCLUSIONS AND IMPLICATIONS:
the evidence gained from this systematic review is very limited. The use of cones
may be helpful for urinary incontinence after childbirth, but further research is
needed.
PMID- 26428192
TI - Engineering the lipid layer of lipid-PLGA hybrid nanoparticles for enhanced in
vitro cellular uptake and improved stability.
AB - Lipid-polymer hybrid nanoparticles (NPs), consisting of a polymeric core and a
lipid shell, have been intensively examined as delivery systems for cancer drugs,
imaging agents, and vaccines. For applications in vaccine particularly, the
hybrid NPs need to be able to protect the enclosed antigens during circulation,
easily be up-taken by dendritic cells, and possess good stability for prolonged
storage. However, the influence of lipid composition on the performance of hybrid
NPs has not been well studied. In this study, we demonstrate that higher
concentrations of cholesterol in the lipid layer enable slower and more
controlled antigen release from lipid-poly(lactide-co-glycolide) acid (lipid
PLGA) NPs in human serum and phosphate buffered saline (PBS). Higher
concentrations of cholesterol also promoted in vitro cellular uptake of hybrid
NPs, improved the stability of the lipid layer, and protected the integrity of
the hybrid structure during long-term storage. However, stabilized hybrid
structures of high cholesterol content tended to fuse with each other during
storage, resulting in significant size increase and lowered cellular uptake.
Additional experiments demonstrated that PEGylation of NPs could effectively
minimize fusion-caused size increase after long term storage, leading to improved
cellular uptake, although excessive PEGylation will not be beneficial and led to
reduced improvement. STATEMENT OF SIGNIFICANCE: This paper reports the
engineering of the lipid layer that encloses a polymeric nanoparticle, which can
be used as a carrier for drug and vaccine molecules for targeted delivery. We
demonstrated that the concentration of cholesterol is critical for the stability
and uptake of the hybrid nanoparticles by dendritic cells, a targeted cell for
the delivery of immune effector molecules. However, we found that hybrid
nanoparticles with high cholesterol concentration tend to fuse during storage
resulting in larger particles with decreased cellular uptake. This problem is
subsequently solved by PEGylating the hybrid nanoparticles. With increased
research and clinical applications of lipid-polymer hybrid nanoparticles in drug
and vaccine delivery, this work will significantly impact the design of the
hybrid nanoparticles for minimized molecule release during circulation and
increased bioavailability of the target molecules.
PMID- 26428194
TI - Nasopharyngeal Carriage, Capsular and Molecular Serotyping and Antimicrobial
Susceptibility of Streptococcus pneumoniae among Asymptomatic Healthy Children in
Egypt.
AB - Streptococcus pneumoniae is a major cause of childhood morbidity and mortality
worldwide with increasing antimicrobial resistance. 600 randomly chosen
asymptomatic healthy children aged 2-60 months attending Alexandria University
Children's Hospital were evaluated for prevalence of nasopharyngeal (NP) carriage
of S. pneumoniae. Prevalence of NP carriage was 29.2% (n = 175/600) Capsular
serotyping was done using Quellung reaction. Vaccine covered serotypes (VST)
represented 67.4% while non-vaccine serotypes (NVST) were 32.6%. The most common
VST isolated were 19F (24.6%), 6B (14.3%) and 6A (10.9%). Confirmation of
serotyping was performed by multiplex PCR which showed 100% concordance with the
Quellung reaction. Antimicrobial susceptibility testing showed penicillin non
susceptibility of 15% (using non-meningitis penicillin MIC breakpoints) and 55%
(using meningitis penicillin MIC breakpoints). Highest resistance was found in
sulphamethoxazole-trimethoprim (55%), tetracyclins (49%), erythromycin (40%) and
clindamycin (25%). This study revealed the epidemiological importance to evaluate
regularly the prevalence, serotypes and the increasing antimicrobial resistance
of S. pneumoniae in the community.
PMID- 26428193
TI - Surface chemistry regulates valvular interstitial cell differentiation in vitro.
AB - The primary driver for valvular calcification is the differentiation of valvular
interstitial cells (VICs) into a diseased phenotype. However, the factors leading
to the onset of osteoblastic-like VICs (obVICs) and resulting calcification are
not fully understood. This study isolates the effect of substrate surface
chemistry on in vitro VIC differentiation and calcified tissue formation. Using
omega-functionalized alkanethiol self-assembled monolayers (SAMs) on gold [CH3
(hydrophobic), OH (hydrophilic), COOH (COO(-), negative at physiological pH), and
NH2 (NH3(+), positive at physiological pH)], we have demonstrated that surface
chemistry modulates VIC phenotype and calcified tissue deposition independent of
osteoblastic-inducing media additives. Over seven days VICs exhibited surface
dependent differences in cell proliferation (COO(-)=NH3(+)>OH>CH3), morphology,
and osteoblastic potential. Both NH3(+)and CH3-terminated SAMs promoted calcified
tissue formation while COO(-)-terminated SAMs showed no calcification. VICs on
NH3(+)-SAMs exhibited the most osteoblastic phenotypic markers through robust
nodule formation, up-regulated osteocalcin and alpha-smooth muscle actin
expression, and adoption of a round/rhomboid morphology indicative of
osteoblastic differentiation. With the slowest proliferation, VICs on CH3-SAMs
promoted calcified aggregate formation through cell detachment and increased cell
death indicative of dystrophic calcification. Furthermore, induction of calcified
tissue deposition on NH3(+) and CH3-SAMs was distinctly different than that of
media induced osteoblastic VICs. These results demonstrate that substrate surface
chemistry alters VIC behavior and plays an important role in calcified tissue
formation. In addition, we have identified two novel methods of calcified VIC
induction in vitro. Further study of these environments may yield new models for
in vitro testing of therapeutics for calcified valve stenosis, although
additional studies need to be conducted to correlate results to in vivo models.
STATEMENT OF SIGNIFICANCE: Valvular interstitial cell (VIC) differentiation and
aortic valve calcification is associated with increased risk of mortality and
onset of other cardiovascular disorders. This research examines effects of in
vitro substrate surface chemistry on VIC differentiation and has led to the
identification of two materials-based initiation mechanisms of osteoblastic-like
calcified tissue formation independent of soluble signaling methods. Such
findings are important for their potential to study signaling cascades
responsible for valvular heart disease initiation and progression as well
providing in vitro disease models for drug development. We have also identified a
VIC activating in vitro environment that does not exhibit confluence induced
nodule formation with promise for the development of tissue regenerating
scaffolds.
PMID- 26428195
TI - Use of Nasal Bubble CPAP in Children with Hypoxemic Clinical Pneumonia-Report
from a Resource Limited Set-Up.
AB - OBJECTIVE: Nasal bubble continuous positive airway pressure (bCPAP) is preferred
in developing economies for easy applicability and low cost. Because its use in
older children is unexplored, we sought to evaluate its utility in hypoxemic
clinical pneumonia. METHODS: Of 330 children (1 month-12 years) with clinical
pneumonia enrolled prospectively over 1 year, those with increased work of
breathing and/or SpO2 <92% received bCPAP delivered via an underwater 'T' tube
through nasal prongs. Proportion requiring intubation despite bCPAP constituted
primary outcome. Incidence of complications, duration of bCPAP and emergency stay
were secondary outcomes. RESULTS: Oxygen was initiated by nasal prongs (NPO2) in
204 (61.8%), and by bCPAP in 110 (33.3%). Sixteen (4.8%) were intubated at the
outset. Fifty-three (25.9%) on NPO2 were shifted to bCPAP for worsening distress
and hypoxemia. Only three (1.8%) from bCPAP group required intubation, of which
one died. Failure rate and complications were negligent. The median emergency
stay was 4 days. CONCLUSIONS: Nasal bCPAP was safe and effective in children with
hypoxemic clinical pneumonia.
PMID- 26428196
TI - Incidence, Etiology and Risk Factors Associated with Neonatal Healthcare
Associated Conjunctivitis: A Prospective Study from a Tertiary Care Hospital in
India.
AB - INTRODUCTION: Healthcare-associated conjunctivitis (HAC) can lead to serious
sequelae including blindness. We conducted a one-year prospective study to
determine the epidemiology of neonatal HAC at a tertiary-care hospital in India.
METHODS: From the neonates fulfilling a set of predefined inclusion criteria,
cases of HAC were diagnosed based on CDC guidelines. Conjunctival swabs, obtained
from neonates with suggestive clinical signs, were processed using standard
protocols. Twenty-eight potential risk factors were analyzed. RESULTS: We
detected 24 cases of HAC among 591 enrolled neonates, with Escherichia coli being
the most frequently isolated microorganism. On multivariate analysis, intubation
at birth (p = 0.046) and orogastric feeding (p = 0.029) had a statistically
significant association with neonatal HAC. Average hospitalization increased from
9.6 to 20.8 days for neonates diagnosed with HAC. CONCLUSION: A standardized case
definition and physician awareness of potential serious sequelae would help
improve detection rates and timely institution of therapy. Hand hygiene could
help control the menace of neonatal HAC.
PMID- 26428197
TI - Cell and Molecular Processes in Cancer Metastasis: an AJP-Cell Physiology set of
Themed Reviews.
PMID- 26428198
TI - In vivo characterization of pancreatic cystic lesions by needle-based confocal
laser endomicroscopy (nCLE): proposition of a comprehensive nCLE classification
confirmed by an external retrospective evaluation.
AB - BACKGROUND AND AIMS: The differential diagnosis of solitary pancreatic cystic
lesions is sometimes difficult. Needle-based confocal laser endomicroscopy (nCLE)
performed during endoscopic ultrasound-fine-needle aspiration (EUS-FNA) enables
real-time imaging of the internal structure of such cysts. Criteria have already
been described for serous cystadenoma and intraductal papillary mucinous neoplasm
(IPMN). The aims of the study were to determine new nCLE criteria for the
diagnosis of pancreatic cystic lesions, to propose a comprehensive nCLE
classification for the characterization of those lesions, and to carry out a
first external retrospective validation . METHODS: Thirty-three patients with a
lone pancreatic cystic lesion were included (CONTACT 1 study). EUS-FNA was
combined with nCLE. Diagnosis was based on either pathology result (Group 1, n =
20) or an adjudication committee consensus (Group 2, n = 13). Six investigators,
unblinded, studied cases from Group 1 and identified nCLE criteria for mucinous
cystic neoplasm (MCN), pseudocyst (PC), and cystic neuroendocrine neoplasm (NEN).
Four external reviewers assessed, blinded, the yield and interobserver agreement
for the newly identified (MCN, PC) and previously described (IPMN, SC) criteria
in a subset of 31 cases. RESULTS: New nCLE criteria were described for MCN (thick
gray line), PC (field of bright particles), and cystic NEN (black neoplastic
cells clusters with white fibrous areas). These criteria correlated with the
histological features of the corresponding lesions. In the retrospective
validation, a conclusive nCLE result was obtained for 74 % of the cases (87 %
"true" and 13 % "false" with respect to the final diagnosis). On this limited
case series, the nCLE criteria showed a trend for high diagnostic specificity
(>90 % for mucinous cysts, 100 % for non-mucinous cysts). CONCLUSIONS: Based on
this newly completed atlas of interpretation criteria, nCLE could facilitate the
diagnosis of pancreatic cystic lesion types.
PMID- 26428199
TI - Erratum to: Evaluation of safety profile of thoracoscopic esophagectomy for
T1bN0M0 cancer using data from JCOG0502: a prospective multicenter study.
PMID- 26428200
TI - Cosmetic outcome of skin adhesives versus transcutaneous sutures in laparoscopic
port-site wounds: a prospective randomized controlled trial.
AB - BACKGROUND: In an elective laparoscopic surgery, the cosmetic outcome becomes
increasingly important. We conducted a study to evaluate the cosmetic outcome 3
months after a laparoscopic procedure and compared skin adhesive (SA) versus
transcutaneous suture (TS). METHODS: A randomized, controlled, prospective study
was conducted at a single study centre in Hamburg, Germany. Seventy-seven
patients undergoing laparoscopic surgery with two lower abdominal port sites met
the study requirements. It was decided randomly which port site would be closed
with SA. The opposite site was closed with TS. Wounds were assessed after 7-12
days and after 3 months. Cosmetic outcome was measured by a visual analogue scale
(VAS) completed by the patient, by the Hollander wound evaluation scale (HWES)
and by the judgement of blinded investigators. RESULTS: Seventy-seven subjects
were randomized. Complete data from the 3-month follow-up visit were available
from 56 patients (72.7 %). The VAS scale ranged from 0 to 100 mm with "0"
representing the best possible cosmetic outcome. Median satisfaction was 2 mm in
the TS group and 3 mm in the SA group. The mean was high in both groups 4.6 (s =
13.1) versus 3.8 mm (s = 4.6). The outcome was neither clinically nor
statistically significant. Cosmetic outcome was assessed by an investigator, and
the HWES showed no difference. In regard to complications, no difference was
found between SA and TS, either. CONCLUSIONS: In conclusion this study
demonstrated that closure of laparoscopic port-site wounds leads to equivalent
outcomes whether SAs or TSs are used. Complications are rare in both methods.
Thus, SAs seem to be a valid alternative to sutures in laparoscopic surgery.
Registration site: www.clinicaltrials.gov . REGISTRATION NUMBER: NCT02179723.
PMID- 26428201
TI - Patient comorbidities increase postoperative resource utilization after
laparoscopic and open cholecystectomy.
AB - BACKGROUND: An understanding of the relationship between patient factors and
healthcare resource utilization represents a major point of interest for
optimizing clinical care and overall net savings, yet maintaining financial
margins for provider revenues. This study aims to review resource utilization
after cholecystectomy in order to characterize patient factors associated with
increased postoperative ED visits and 30-day readmissions. METHODS: A total of
53,632 open and laparoscopic cholecystectomies were reviewed from July 2009 to
December 2010 in a large private payer claims database. ICD-9 and CPT codes were
available for each event, as well as basic demographics. Data regarding 30-day
postoperative resource utilization metrics (emergency department visits and
inpatient hospitalizations) were analyzed and stratified by key patient
comorbidities. Differences between subgroups were evaluated with univariate and
multivariable methods. RESULTS: Of the 53,632 patients studied, 71.2 % (38,171)
were female and 28.8 % (15,461) male. Resource utilization within 30 days of
surgery included: 6.6 % (3538) of patients with an ED visit and 7.7 % (4103) with
an inpatient hospitalization. The most common comorbidities in the study
population were: hypertension, hyperlipidemia, GERD/hiatal hernia, and diabetes
mellitus. Patients with heart failure, cirrhosis, and a history of MI or acute
ischemic heart disease all had a significant association with postoperative ED
visit and the highest likelihood of inpatient hospitalization. Angina, diabetes,
and hypertension similarly increased both ED utilization and inpatient
readmissions to a lesser but still significant extent. Although patients with
GERD/hiatal hernia and sleep apnea had a significant association with ED use,
they did not have an increased likelihood of readmission. CONCLUSIONS: Patient
comorbidity indexing plays a major role in clinical risk stratification and
resource utilization for cholecystectomy. These factors should be considered in
bundled reimbursement packages and in the creation of preventive postoperative
ambulatory strategies given their role in determining potential resource
utilization in the postoperative setting.
PMID- 26428202
TI - Simple versus reinforced cruroplasty in patients submitted to concomitant
laparoscopic sleeve gastrectomy: prospective evaluation in a bariatric center of
excellence.
AB - BACKGROUND: Crural closure in addition to laparoscopic sleeve gastrectomy (LSG)
represents a valuable option for the synchronous management of morbid obesity and
hiatal defects, providing good outcomes in terms of weight loss and
gastroesophageal reflux disease (GERD) symptoms control. The aim of this
prospective study was to evaluate the safety and effectiveness of the reinforced
cruroplasty during LSG compared with a concurrent group of simple cruroplasty.
METHODS: The study groups included 96 morbidly obese patients who underwent
simultaneous LSG and cruroplasty. Group A: 48 patients with hiatal areal defect
<4 cm(2) and normal pillars (simple posterior cruroplasty); group B: 48 patients
with hiatal areal defect >4 and <8 cm(2) with weakness of the right pillar (on
lay synthetic absorbable mesh-reinforced cruroplasty). Upper GI symptoms were
assessed by Roma III standard questionnaire. Endoscopy, imaging, esophageal 24-h
pH monitoring and HR manometry were performed in cases of persistent or recurrent
symptoms after surgery. RESULTS: Mortality rate was nil. The conversion rate to
open was 1 %. Intra-operative diagnosis of hiatal hernia occured in 41 patients
(42.7 %). Mesh-related complications were none. Perioperative complications
occurred in four patients (4.1 %). After 19- to 21-month follow-up, GERD symptom
remission occurred in 89 % of patients. GERD symptoms were detected
postoperatively in eight patients: six in group A (five symptomatic and
radiological recurrences and one persistent) and two in group B (one persistent
and one de novo GERD) (P < 0.05). CONCLUSIONS: The synthetic absorbable mesh
offers an effective option for crural repair during LSG with no clinical
recurrences at 19 months. The midterm results of this prospective comparative
study evaluating two different technical options for cruroplasty confirm that the
simultaneous procedures are safe and cruroplasty is effective in mild-to-moderate
GERD control .
PMID- 26428203
TI - Adverse Selection in the Children's Health Insurance Program.
AB - This study investigates whether new enrollees in the Alabama Children's Health
Insurance Program have different claims experience from renewing enrollees who do
not have a lapse in coverage and from continuing enrollees. The analysis compared
health services utilization in the first month of enrollment for new enrollees
(who had not been in the program for at least 12 months) with utilization among
continuing enrollees. A second analysis compared first-month utilization of those
who renew immediately with those who waited at least 2 months to renew. A 2-part
model estimated the probability of usage and then the extent of usage conditional
on any utilization. Claims data for 826 866 child-years over the period from 1999
to 2012 were used. New enrollees annually constituted a stable 40% share of
participants. Among those enrolled in the program, 13.5% renewed on time and
86.5% of enrollees were late to renew their enrollment. In the multivariate 2
part models, controlling for age, gender, race, income eligibility category, and
year, new enrollees had overall first-month claims experience that was nearly $29
less than continuing enrollees. This was driven by lower ambulatory use. Late
renewals had overall first-month claims experience that was $10 less than
immediate renewals. However, controlling for the presence of chronic health
conditions, there was no statistically meaningful difference in the first-month
claims experience of late and early renewals. Thus, differences in claims
experience between new and continuing enrollees and between early and late
renewals are small, with greater spending found among continuing and early
renewing participants. Higher claims experience by early renewals is attributable
to having chronic health conditions.
PMID- 26428204
TI - Flare Rate in Patients with Rheumatoid Arthritis in Low Disease Activity or
Remission When Tapering or Stopping Synthetic or Biologic DMARD: A Systematic
Review.
AB - OBJECTIVE: To evaluate the risk of having a disease flare in patients with
rheumatoid arthritis (RA) with low disease activity (LDA) or in remission when
deescalating (tapering or stopping) disease-modifying antirheumatic drug (DMARD)
therapy. METHODS: A search in medical databases including publications from
January 1950 to February 2015 was performed. Included were trials and
observational studies in adults with RA who were in LDA or remission, evaluating
>= 20 patients tapering or stopping DMARD. Flare rates had to have been reported.
A metaanalysis was performed on studies deescalating tumor necrosis factor (TNF)
blockers. RESULTS: Four studies evaluated synthetic DMARD. Flare rates ranged
from 8% at 24 weeks to 63% at 4 months after deescalation. Fifteen studies
reported on TNF blockers. Estimated flare rates by metaanalysis on studies
tapering or stopping TNF blockers were 0.26 (95% CI 0.17-0.39) and 0.49 (95% CI
0.27-0.73) for good-quality and moderate-quality studies, respectively. Flare
rates in 3 studies stopping tocilizumab were 41% after 6 months, 55% at 1 year,
and 87% at 1 year. Flare rates in 3 studies deescalating abatacept were 34% at 1
year, 41% at 1 year, and 72% at 6 months. Five studies evaluating radiographic
progression in patients deescalating treatment all found limited to no
progression. CONCLUSION: Results suggest that more than one-third of patients
with RA with LDA or in remission may taper or stop DMARD treatment without
experiencing a disease flare within the first year. Dose reduction of TNF
blockers results in lower flare rates than stopping and may be noninferior to
continuing full dose. Radiological progression after treatment deescalation
remains low, but may increase slightly.
PMID- 26428206
TI - Concomitant Methotrexate Protects Against Total Knee Arthroplasty in Patients
with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitors.
AB - OBJECTIVE: To determine the effects of concomitant methotrexate (MTX) on the
incidence of total knee arthroplasty (TKA) resulting from the progression of
joint destruction in patients with rheumatoid arthritis (RA) during longterm
treatment with tumor necrosis factor (TNF) inhibitors. METHODS: A total of 155
patients with RA (310 knee joints) received TNF inhibitors at our institute
between May 1, 2001, and May 31, 2008. A total of 111 symptomatic (tender and/or
swollen) knee joints in 68 patients were retrospectively studied over the course
of a minimum of 5 years of followup. The median (interquartile range) followup
period was 8.1 (7.0-9.3) years. All data were analyzed using the knee joint as
the statistical unit of analysis. TKA during treatment with TNF inhibitors was
used as the outcome variable in predictive analyses. The cumulative incidence of
TKA was compared by concomitant or no MTX use (MTX+/-). RESULTS: There were 79
subjects (71%) who received concomitant MTX. According to Kaplan-Meier estimates,
the cumulative incidence of TKA for the MTX+ group was significantly lower than
that for the MTX- group (24% vs 45% at 5 yrs, respectively, p = 0.035).
Multivariate analysis using the Cox proportional hazards model revealed that
concomitant MTX (HR 0.44, 95% CI 0.22-0.89), Larsen grade (HR 2.93, 95% CI 1.94
4.41), and older age at baseline (HR 1.04, 95% CI 1.01-1.08) were independent
predictors of TKA. CONCLUSION: Concomitant MTX reduces the incidence of TKA by
56% in patients with RA during longterm treatment with TNF inhibitors.
PMID- 26428207
TI - Subclinical Atherosclerosis Is Not Accelerated in Patients with Ankylosing
Spondylitis with Low Disease Activity: New Data and Metaanalysis of Published
Studies.
AB - OBJECTIVE: Chronic inflammatory rheumatic diseases are associated with
accelerated atherosclerosis, but data in ankylosing spondylitis (AS) are limited
and the relative contribution of inflammation versus classical cardiovascular
(CV) risk factors remains a matter of controversy. We addressed this in an
original study and a metaanalysis of previous studies. METHODS: Atheromatic
plaques in carotid and femoral arteries, carotid hypertrophy [intima-media
thickness (IMT), cross-sectional area], and carotid stiffness by ultrasound, as
well as aortic stiffness by pulse wave velocity, were examined in consecutive
nondiabetic, CV disease (CVD)-free patients with AS. Healthy individuals
carefully matched 1:1 with patients for age, sex, smoking habits, hyperlipidemia,
and hypertension served as controls. A metaanalysis of original studies that
examined subclinical atherosclerosis in patients with AS versus controls with
comparable CVD risk factors was also performed. RESULTS: Carotid and femoral
atheromatic plaques were slightly less prevalent compared with controls in a
contemporary cohort consisting of 67 patients with AS (82% men), aged 47.5 +/-
12.5 years (mean +/- SD), with a median disease duration of 12 years and a Bath
AS Disease Activity Index (BASDAI) of 1.8 (interquartile range 0.4-3.6), of whom
66% were receiving anti-tumor necrosis factor (TNF) treatment. Carotid
hypertrophy and stiffness, as well as aortic stiffness, were similar between
patients and their matched controls. Metaanalysis of all published studies
revealed a significantly increased carotid IMT, but not plaque burden, in AS
versus controls. Notably, however, increased IMT was not evident in studies
involving patients with low disease activity (mean BASDAI < 4) or in those
studies that included > 50% of patients treated with anti-TNF. CONCLUSION: Low AS
disease activity is not associated with accelerated atherosclerosis.
PMID- 26428205
TI - Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying
Dosing Controversies and Improving Adherence.
AB - OBJECTIVE: Hydroxychloroquine (HCQ) is used for its effect on systemic lupus
erythematosus (SLE) disease activity and longterm benefits. This can be limited
by adherence. One way to assess adherence is to measure blood levels. Conflicting
data exist regarding blood levels and disease activity. There is disagreement
about dosing; rheumatologists recommend weight-based dosing while some other
specialists advocate height-based "ideal body weight" dosing. METHODS: Patients
were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis,
the dose was 200 mg after each session, and in renal insufficiency it was 200
mg/day. Levels were measured at each visit with a therapeutic range of 500-2000
ng/ml. Patients were divided according to baseline blood level. To assess the
effect of measurement and counseling on adherence, we compared the proportion of
patients with a level of 500 ng/ml or higher based on the number of prior
assessments. RESULTS: The proportion of patients with HCQ levels in the
therapeutic range differed significantly by age, sex, and Vitamin D level. There
was a trend toward lower levels with renal failure. Blood levels were similar
regardless of height and ideal body weight. Comparing those with undetectable,
subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease
Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were
therapeutic, and by the third measurement this increased to 80% (p <= 0.0001).
CONCLUSION: There was a trend toward higher disease activity with lower HCQ
levels. Renal failure dosing led to suboptimum levels. We show that weight-based
dosing (max 400 mg daily) is appropriate and that height does not appear to
influence levels. Measurement, counseling, and repeated testing can increase
adherence rates.
PMID- 26428208
TI - Fragility Fractures in Patients with Rheumatoid Arthritis and Osteoarthritis
Compared with the General Population.
AB - OBJECTIVE: To determine the rate ratios of hip and distal radius fractures in
patients with rheumatoid arthritis (RA), hip osteoarthritis (OA), and knee OA.
METHODS: Cohort study using healthcare data (1998-2012) covering the entire
population of the Skane region of Sweden. RESULTS: We found an increased rate of
hip fracture in both female [standardized fracture rate ratio (SFR) 1.54, 95% CI
1.40-1.70] and male patients with RA (SFR 1.81, 95% CI 1.51-2.17). The hip
fracture rate in female OA was reduced by 10-20%, and trochanteric fracture
tended to have a higher rate ratio compared with the cervical. CONCLUSION: The 50
80% increased rate of hip fracture adds to the total burden of RA while the
shifted distribution of cervical/trochanteric fractures in OA is in support of
subchondral bone alterations.
PMID- 26428209
TI - Effect of Urate Lowering Therapy on Renal Disease Progression in Hyperuricemic
Patients with Chronic Kidney Disease.
AB - OBJECTIVE: To determine whether urate lowering therapy (ULT) could delay renal
disease progression in hyperuricemic patients with chronic kidney disease (CKD).
METHODS: We performed a retrospective review of hyperuricemic patients with stage
3 CKD followed from September 2005 to July 2014 in Dongguk University Ilsan
Hospital, Goyang, Korea. A total of 158 eligible patients were identified and 65
of them were treated with ULT in addition to the usual CKD management. We divided
the patients according to the use of ULT and compared the estimated glomerular
filtration rate (eGFR) change from baseline value and the proportion of renal
disease progression (decline of eGFR > 30% of the baseline value, initiation of
dialysis or eGFR < 15 ml/min/1.73m(2)) at the time of last followup. Risk factors
for renal disease progression were identified by logistic regression analysis.
RESULTS: After a median followup of 118.5 weeks (minimum 25, maximum 465), the
ULT group showed better outcomes compared to the non-ULT group in terms of eGFR
change from baseline (-1.19 +/- 12.07 vs -7.37 +/- 11.17 ml/min/1.73 m(2), p =
0.001) and the proportion of renal disease progression (12.3% vs 27.9%, p =
0.01). Goal-directed ULT showed better clinical outcomes compared to maintaining
the initial ULT dose. Actual (area under the SUA-time curve adjusted by total
observation time period) serum uric acid was significantly associated with the
risk of renal disease progression (p for trend = 0.04) and actual serum uric acid
level < 7 mg/dl reduced the risk of renal disease progression by 69.4%.
CONCLUSION: ULT significantly delayed renal disease progression in hyperuricemic
patients with CKD. Goal-directed ULT seems to be better than continuing the
initial ULT prescription.
PMID- 26428210
TI - Synthesis of a-Alkylated Ketones via Tandem Acceptorless Dehydrogenation/a
Alkylation from Secondary and Primary Alcohols Catalyzed by Metal-Ligand
Bifunctional Iridium Complex [Cp*Ir(2,2'-bpyO)(H2O)].
AB - A new strategy for the synthesis of alpha-alkylated ketones via tandem
acceptorless dehydrogenation/alpha-alkylation from secondary and primary alcohols
was proposed and accomplished. In the presence of metal-ligand bifunctional
iridium complex [Cp*Ir(2,2'-bpyO)(H2O)], various desirable products were obtained
in high yields. Compared with previous methods for the direct dehydrogenative
coupling of secondary alcohols with primary alcohols to alpha-alkylated ketones,
this protocol has obvious advantages including complete selectivity for alpha
alkylated ketones and more environmentally benign conditions. Notably, the study
also exhibited the potential to develop tandem reactions catalyzed using a metal
ligand bifunctional iridium complex.
PMID- 26428211
TI - Risk of ectopic pregnancy is linked to endometrial thickness in a retrospective
cohort study of 8120 assisted reproduction technology cycles.
AB - STUDY QUESTION: Is endometrial combined thickness (ECT) measured prior to embryo
transfer (ET) associated with ectopic pregnancy (EP)? SUMMARY ANSWER: Following
IVF, the risk of EP is 4-fold increased in women with an ECT of <9 mm compared
with women with an ECT of >12 mm. WHAT IS KNOWN ALREADY: Known risk factors for
EP include tubal damage, maternal cigarette smoking and endometriosis. EP is also
more common following IVF but the underlying causes for this remain unclear.
STUDY DESIGN, SIZE, DURATION: Retrospective cohort study restricted to all IVF
cycles leading to a pregnancy (betahCG > 50 IU/l) between January 2006 and
December 2014. A total of 6465 patients achieved a pregnancy in 8120 cycles.
Cycles using preimplantation genetic screening or donor oocytes were excluded.
PARTICIPANTS/MATERIALS, SETTING, METHODS: This cohort consists of 6465 patients
achieving a pregnancy in 6920 stimulated cycles with fresh embryo transfers (STIM
ET) and 1200 hormone replacement therapy frozen embryo transfers (HRT-FET) cycles
at a private IVF unit (Monash IVF, Melbourne, Australia). ECT was the primary
independent variable of interest; the primary outcome was a diagnosis of EP. The
dataset was analysed using binary logistic general estimating equations (SPSS
v22.0) to calculate odds ratio (OR) for EP adjusted for known confounders (aOR).
There was no loss to follow-up in the dataset. MAIN RESULTS AND THE ROLE OF
CHANCE: The study groups did not differ significantly prior to IVF treatment.
After adjusting for confounders, ECT remained statistically significant as an
independent risk factor for EP. Compared with women with an ECT of <9 mm, women
with an ECT of 9-12 mm had an aOR of 0.44 (95% CI 0.29-0.69, P < 0.01) and women
with an ECT > 12 mm had an aOR of 0.27 (95% CI 0.10-0.77, P = 0.01). These
differences remained statistically significant after performing a sensitivity
analysis excluding HRT-FET, smokers and patients with tubal infertility.
LIMITATIONS, REASONS FOR CAUTION: The study design is retrospective, and it is
possible that not all confounders have been accounted for. Measurement of ECT was
performed by highly trained sonographers, but some inconsistency between
individuals may be present. WIDER IMPLICATIONS OF THE FINDINGS: Our group has
previously demonstrated an increased risk of placenta praevia with increased ECT.
These new findings suggest that the directionality of the uterine peristalsis
waves matters more than their frequency or amplitude. Combining the data from
both studies we now hypothesize that increased ECT is a marker for increased
fundus-to-cervix uterine peristalsis, explaining both the increased placenta
praevia risk and the lower EP risk. Further prospective studies are required to
confirm these observations.
PMID- 26428212
TI - Spermatogenesis in tumor-bearing testes in germ cell testicular cancer patients.
AB - STUDY QUESTION: What are the factors that might indicate a greater likelihood of
success in oncologic testicular sperm extraction (onco-TESE)? SUMMARY ANSWER:
Smaller tumor diameter and greater noncancerous testicular tissue width (NCTW)
are positive predictors of spermatogenesis in patients with testicular germ cell
tumors (TGCTs). WHAT IS KNOWN ALREADY: Onco-TESE is a key modality for fertility
preservation in cases of inadequate pretreatment sperm collection and azoospermic
men with testicular cancer. TGCTs are known to reduce sperm quality such that ~
10% of these patients are azoospermic, making surgical TESE at the same time as
orchiectomy their only means of fertility preservation. STUDY DESIGN, SIZE,
DURATION: This study is a retrospective analysis performed in a single university
hospital from 2002 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS:
Participants were 102 male patients (104 testes) who underwent inguinal
orchiectomy and were diagnosed with a germinoma. In each specimen, the Johnsen
Score Count (JSC) in seminiferous tubules at each established distance from the
tumor margin (1, 2.5, 5, 7.5, 10 and 12.5 mm) was determined. We analyzed the
relations between age, tumor histopathologic type, tumor size (maximum diameter),
distance from the tumor, non-tumor tissue width and JSC. MAIN RESULTS AND THE
ROLE OF CHANCE: The 104 specimens consisted of 78 seminomas and 26 non
seminomatous TGCTs. The mean +/- SD JSC was 4.7 +/- 2.4 in seminomas and 3.9 +/-
2.5 in non-seminomatous germ cell tumors, with no significant difference between
the two subtypes. Single regression analysis showed that tumor diameter was
significantly negatively correlated with spermatogenesis (RC = -0.422, P <
0.001). Multiple linear regression analysis also showed that tumor diameter had a
negative influence on spermatogenesis (RC = -0.437, P < 0.001). The greater the
distance the seminiferous tubules from the tumor, the better the preservation of
spermatogenesis. Mature spermatozoa were identified in 93.0% of patients with a
NCTW >= 7.5 mm and in 41.3% of those with NCTW < 7.5 mm (P < 0.001). LIMITATIONS,
REASONS FOR CAUTION: Study data were obtained retrospectively, which might have
affected the quality of data. We were unable to compare spermatogenesis
determined using preoperative seminograms with that determined
histopathologically. It was not possible to evaluate spermatogenesis in the total
volume of noncancerous testicular tissue. WIDER IMPLICATIONS OF THE FINDINGS:
When Onco-TESE is conducted at sites distant from tumors, the rate of sperm
extraction is high and contamination by tumor cells can be prevented. By
measuring non-testicular cancerous margin before the operation, the possibility
of sperm extraction can be predicted and biopsy of the contralateral testis can
be considered based on the results.
PMID- 26428214
TI - Introduction to the special issue on chemical glycobiology: all the aspects are
important.
PMID- 26428213
TI - Linked data research: a valuable tool in the ART field.
PMID- 26428215
TI - Sudden occurrence of Roth spots and retinal hemorrhages following endoscopic
adhesiolysis: an SD-OCT evaluation.
AB - PURPOSE: To document the occurrence of Roth spots and retinal hemorrhages by
spectral-domain optical coherence tomography (SD-OCT) following endoscopic
adhesiolysis for failed back surgery syndrome. METHODS: Case report. RESULTS: A
47-year-old patient noted progressive and bilateral visual loss immediately after
epidural endoscopy and endoscopic adhesiolysis. Funduscopic examination showed
multiple Roth spots and retinal hemorrhages at the posterior pole and the retinal
midperiphery in both eyes. Spectral-domain optical coherence tomography
demonstrated that Roth spots involved the inner retina, while dot hemorrhages
involved the outer retina. Most retinal hemorrhages and Roth spots resolved over
6 weeks, with complete functional recovery in both eyes. However, SD-OCT revealed
multiple areas of disruption of the outer retinal layers in the left eye.
CONCLUSIONS: Roth spots and retinal hemorrhages can occur after endoscopic spinal
surgery. Although hemorrhages resolve quickly over few weeks, SD-OCT can
demonstrate that retinal damage might persist, especially in the outer retina.
This finding may explain cases of incomplete recovery of visual function after
complicated endoscopic adhesiolysis.
PMID- 26428216
TI - Atlas OCT: angiography in AMD: comparison with multimodal imaging.
PMID- 26428217
TI - Choroidal thickness in diabetic retinopathy in relation to long-term systemic
treatments for diabetes mellitus.
AB - PURPOSE: To measure central choroidal thickness (CCT) in patients with diabetic
retinopathy (DR) and analyze the correlation with clinical backgrounds regarding
medications for diabetes mellitus (DM). METHODS: We retrospectively identified 86
patients with DR (172 eyes) and 43 healthy subjects (57 eyes) who underwent
spectral-domain optical coherence tomography. Among the 86 patients with DM who
had received no intraocular treatments, 61 were diabetic patients who had
continuously received systemic treatments for DM (under treatment group). Twenty
five were patients who had discontinued the treatments or had not received any
treatment for DM until this study started (no treatment group). RESULTS: The
results of CCT acquired by 2 masked raters showed a significant correlation
coefficient (r = 0.98), indicating high reproducibility in this study. No
correlation of CCT was noted between normal (272 +/- 71 um) and DM eyes (264 +/-
77 um), the presence of diabetic macular edema, or CCT and the severity of DR in
the patients examined. Interestingly, there was a significant decrease in CCT
(175 +/- 42 um) in eyes with mild/moderate nonproliferative DR (NPDR) in the no
treatment group (p<0.05), whereas CCT was prominently thicker in eyes with severe
NPDR (354 +/- 76 um) and proliferative DR (286 +/- 74 um) than in eyes without
DR. CONCLUSIONS: This study demonstrated that CCT was significantly decreased in
the presence of mild/moderate NPDR in the no treatment group, suggesting that a
continuously high blood sugar state caused by insufficient treatments for DM may
facilitate vascular damage in the choroid in the early stage of DR.
PMID- 26428218
TI - Enhanced depth imaging optical coherence tomography in adult-onset foveomacular
vitelliform dystrophy.
AB - PURPOSE: To compare mean choroidal thickness in patients with adult-onset
foveomacular vitelliform dystrophy (AOFVD) and healthy subjects, to analyze
patients with AOFVD in order to evaluate choroidal thickness disease-related
changes, also in relation to the different stages of AOFVD disease and to the
retinal pigment epithelium (RPE) features, and to correlate mean choroidal
thickness with age in both groups. METHODS: In this prospective observational
cross-sectional study, a total of 63 eyes of 51 consecutive subjects were
examined, consisting of a control group (n = 28 eyes) and the AOFVD group (n = 35
eyes). A complete ophthalmologic examination, fundus autofluorescence, and
spectral-domain optical coherence tomography were performed in all patients.
RESULTS: Mean subfoveal choroidal thickness was 214.78 +/- 62.35 um in healthy
subjects and 222.31 +/- 73.29 um in the AOFVD group (p = 0.33). In the
vitelliruptive group, the mean choroidal thickness was significantly thicker than
in the control group at each choroidal location. Mean choroidal thickness was
significantly increased in the pseudohypopyon stage when compared to the
vitelliform one (+66.34 um, p = 0.02). Eyes with subretinal fluid (SRF) showed
significantly thicker choroid when compared with those without SRF. No
significant correlations were found between age and choroidal thickness in the
study group. CONCLUSIONS: The study of the choroid in patients with AOFVD
suggested a possible role in the pathologic changes during the different stages
of disease, and could help us to evaluate progression of the disease. Greater
choroidal thickness associated with SRF and RPE bumps are signs of RPE
alterations and could be related to evolution of the AOFVD lesion to a different
stage.
PMID- 26428219
TI - Study of spectral-domain optical coherence tomography in children: normal values
and influence of age, sex, and refractive status.
AB - PURPOSE: To establish normal values for retinal nerve fiber layer (RNFL), macular
thickness, and macular volume in children using spectral-domain optical coherence
tomography (OCT). METHODS: A descriptive cross-sectional study was performed in
healthy children between 3 and 14 years of age. Each child underwent a
comprehensive ophthalmic examination that included 3 OCT scans with Spectralis
(Heidelberg Engineering, Heidelberg, Germany). All measurements were performed by
the same operator, and one eye was randomly selected. The influence of age, sex,
and refraction on OCT measurements was analyzed. RESULTS: The sample consisted of
162 Caucasian subjects, mean age 8.1 +/- 3.03 years. The spherical equivalent was
0.03 +/- 0.19 D (range +/-4 D, astigmatism <1 D). The average values were 263.69
+/- 4.54 um for central macular thickness, 0.21 +/- 0.01 mm3 for central macular
volume, and 100.45 +/- 1.98 um for RNFL. A significant correlation between RNFL
and spherical equivalent was found for the nasal (p = 0.001), inferior (p =
0.009), and inferior nasal (p = 0.005) sectors. No differences were found with
regard to sex (p>0.05). However, central macular thickness and central macular
volume were correlated with age (p = 0.027, p = 0.02). CONCLUSIONS: This study
provides reference values for macular thickness, macular volume, and RNFL in
healthy children.
PMID- 26428220
TI - Intraocular surgery with melphalan irrigation for vitreous hemorrhage in an only
eye with retinoblastoma.
AB - PURPOSE: To illustrate the successful outcome of pars plana vitrectomy (PPV) with
melphalan irrigation for vitreous hemorrhage (VH) with suspected viable
retinoblastoma. Despite the high risk of intraocular surgery, it was performed to
preserve the only potentially seeing eye with treated retinoblastoma. METHODS:
Vitreous hemorrhage occurred in the only eye of a 4-year-old boy after treatment
for recurrent multifocal group C retinoblastoma with systemic chemotherapy
(carboplatin, etoposide, and cyclophosphamide; and vincristine, cyclophosphamide,
and doxorubicin), ruthenium brachytherapy with plaque repositioning, cryotherapy,
and external radiotherapy. The VH developed 8 months after repeated brachytherapy
with subsequent intravitreal melphalan chemotherapy. The patient's parents
refused to remove the eye. The fellow eye was enucleated earlier because of VH
and secondary glaucoma, without histologic signs of a viable tumor. Pars plana
lensectomy, 25-G vitrectomy with melphalan irrigation (5 MUg/mL), and silicone
oil tamponade were performed. RESULTS: No ophthalmoscopic or morphologic signs of
a viable tumor were detected. Four months later, the silicone oil was removed.
Visual acuity was 20/200 with aphakic correction. Follow-up for 34 months
revealed no signs of tumor recurrence or dissemination. CONCLUSIONS: Despite the
high risk of intraocular surgery, the need to preserve the only potentially
seeing eye with treated retinoblastoma may require PPV. Thus, in unclear cases of
VH with suspected viable tumor, PPV with intraocular melphalan irrigation, with
caution, may be a reasonable procedure.
PMID- 26428222
TI - Intravitreal injection of recombinant tissue plasminogen activator in submacular
hemorrhage: case series.
AB - PURPOSE: To report the safety and efficacy of intravitreal recombinant tissue
plasminogen activator (rtPA) with gas for managing submacular hemorrhage.
METHODS: Patients with submacular hemorrhage centered in or close to the fovea
underwent hemorrhage displacement with intravitreal injection of rtPA (50
MUg/0.05 mL) followed by gas injection (0.3 mL SF6). Anatomic and visual outcomes
are described. RESULTS: Exudative age-related macular degeneration (AMD) (n = 4)
and blunt trauma (n = 2) were the etiologies of submacular hemorrhage in this
sample. Intravitreal injection of rtPA decreased the extent of submacular
hemorrhage in all eyes, with complete hemorrhage displacement in 2 and partial
displacement in 4. Visual acuity remained stable (n = 4) or improved (n = 2)
after the procedure. Improvements in anatomic and visual outcomes were less
evident in exudative AMD cases, which also had longer hemorrhage duration.
Recurrence occurred only in 1 eye. No evident rtPA-associated retinal toxicity
was observed. CONCLUSIONS: Untreated submacular hemorrhage has poor visual
prognosis. Our results suggest that rtPA injection is a minimally invasive,
simple, inexpensive procedure with few related complications. Cost-benefit of
this injection seems acceptable.
PMID- 26428221
TI - Receiver operating characteristic curve to predict anti-VEGF resistance in
retinal vein occlusions and efficacy of Ozurdex.
AB - PURPOSE: Current treatment paradigms for macular edema associated with retinal
vein occlusions (RVO) often involve initial treatment with anti-vascular
endothelial growth factor (VEGF) agents, then switching to intravitreal
dexamethasone implant (IDI; Ozurdex, Allergan, Parsippany, NJ) for poor
responders. However, many patients undergo multiple injections prior to being
declared a nonresponder. We devised a method for prediction of poor anti-VEGF
response after one injection, and show that these patients subsequently respond
well to IDI. METHODS: This study is a retrospective consecutive interventional
case series of patients with RVO receiving anti-VEGF agents that were switched to
IDI. Patients were categorized as nonresponders to anti-VEGF agents (edema did
not improve) or responders (edema improved, but switched to IDI for longer
treatment duration). Receiver operating characteristics (ROC) curve analysis was
used to determine cutoffs of reduction in central retinal thickness (CRT) to
predict poor response to anti-VEGF treatment. RESULTS: Twenty-three patients met
inclusion criteria. There were 14 nonresponders and 9 responders. The ROC curve
analysis found that the maximal sensitivity and specificity in correctly
identifying responders to anti-VEGF therapy was those with >25% reduction in CRT
1 month after 1 anti-VEGF treatment (sensitivity 0.89, specificity 0.79, area
under the curve 0.93). After IDI placement, anti-VEGF nonresponders showed
significant improvement in visual acuity (VA) (p = 0.02) and CRT (p = 0.01).
CONCLUSIONS: In patients with macular edema secondary to RVOs, a reduction in CRT
by <=25%, 1 month after 1 anti-VEGF injection, is predictive of poor response to
anti-VEGF treatment. These patients may benefit from earlier conversion to IDI
treatment, which in our study, resulted in improved VA and CRT.
PMID- 26428223
TI - Angiotensin-(1-7) enhances the effects of angiotensin II on the cardiac
sympathetic afferent reflex and sympathetic activity in rostral ventrolateral
medulla in renovascular hypertensive rats.
AB - Excessive sympathetic activity propels the pathogenesis and progression of organ
damage in hypertension. Enhanced cardiac sympathetic afferent reflex (CSAR) is
involved in sympathetic activation in hypertension. Given the important role of
the renin-angiotensin (Ang) system in regulating sympathetic outflow and
cardiovascular activity, the present study aimed to investigate the roles of Ang
(1-7) in Ang II-induced CSAR and the sympathetic activation responses in the
rostral ventrolateral medulla (RVLM) of hypertensive rats. The two-kidney one
clip (2K1C) method was used to induce renovascular hypertension. Responses of
renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to
epicardial application of capsaicin were used to evaluate the CSAR in sinoaortic
denervated and cervical-vagotomized rats with anesthesia. Both Ang II and Ang-(1
7) in the RVLM caused greater increases in RSNA and MAP in 2K1C rats than in sham
operated (sham) rats and enhanced CSAR independently. RVLM pretreatment with Ang
(1-7) dose dependently augmented the effects of Ang II on RSNA, MAP, and CSAR in
2K1C rats. Mas receptor antagonist A-779 in the RVLM exhibited more powerful
inhibitory effects on RSNA, MAP, and CSAR than the Ang II type 1 (AT1) receptor
antagonist losartan. The expression of both the AT1 receptor and Mas receptor
proteins in the RVLM increased, but neither the Ang II nor Ang-(1-7) levels in
the RVLM changed significantly in the 2K1C rats compared with the sham rats.
These results indicate that Ang-(1-7) in the RVLM enhances the CSAR and
sympathetic output not only by itself but also through enhancing the effects of
Ang II in renovascular hypertensive rats. Both endogenous Ang-(1-7) and Ang II in
the RVLM contribute to the enhanced CSAR and sympathetic activation in
renovascular hypertension.
PMID- 26428224
TI - Use of gastrografin in the management of worm-induced small bowel obstruction in
children.
AB - OBJECTIVE: Ascaris-induced small bowel obstruction (SBO) is a common sequel of
Ascaris lumbricoides (AL) infestation. Most cases respond to conservative
treatment practiced in different centers worldwide. We conceived a prospective
randomized trial to compare the conservative treatment with gastrografin
administered in addition to the conservative treatment. STUDY DESIGN: This
prospective randomized study was conducted between January 2011 and June 2014 at
Department of Paediatric and Neonatal Surgery, a tertiary-care hospital. Patients
were divided into two groups, one group received conservative treatment and the
other received gastrografin in addition to conservative treatment. Forty patients
having uncomplicated AL-induced SBO were included in each group. Gastrografin was
administered through nasogastric tube and serial clinical and radiological
monitoring was performed. The duration of hospital stay, time between admission
and first oral feed, passage of worms/flatus were compared in the two groups.
Student's t test was used for comparing these variables. RESULTS: Average time
for passage of flatus or worms and resolution of abdominal signs and was shorter
in gastrografin group as compared to the conservative group. This difference was
found to be statistically significant. The average duration of hospital stay in
gastrografin group was 25.20 +/- 8.01 h whereas it was 61.12 +/- 14.64 h in the
conservative group (P < 0.001). The difference in the operation rate was
statistically insignificant (2 in gastrografin group and 3 in the conservative
group).No serious adverse reaction was noted after gastrografin administration.
CONCLUSION: Use of gastrografin resulted in faster relief of signs and symptoms
of AL-induced SBO, early passage of worms/flatus and return to oral feeds.
However, the role of gastrografin role in reducing the likelihood of laparotomy
remains inconclusive. Adverse effects of gastrografin can be prevented if it is
used in well-hydrated patients.
PMID- 26428225
TI - The Primacy of the Social and Sociogenesis.
AB - It has become a truism to state that cultural characteristics (knowledge,
identity, practices) are "socially constructed." However, critics point out that
the social overwhelmingly is understood as a context-a trivial sense of the
social-and that the real social nature of human practices tends not to be shown.
The Russian social psychologist L. S. Vygotsky assumes in his late work a primacy
of the social such that all higher psychological functions are social relations
between people before they are functions. As a result, human development occurs
in and as sociogenesis. Grounded in an ethnomethodological take on the social,
the purpose of this article is to articulate and develop this unrecognized and
unheeded, radical aspect of the late Vygotskian theory, thereby going beyond
wrote and may have intended.
PMID- 26428227
TI - [Impact of anastomotic leakage on long-term survival in mid-to-low rectal
cancer].
AB - BACKGROUND: The occurrence of anastomotic leakage (AL) after sphincter preserving
anterior rectal resection in patients with rectal cancer is associated with
increased morbidity and mortality. The impact of AL on long-term survival has,
however, still not been sufficiently investigated and is currently the subject of
controversial discussion. OBJECTIVES: The aim of this study was to investigate
the impact of AL on long-term survival in patients with Union of International
Cancer Control (UICC) (y)0-III stage mid-to-low rectal cancer who underwent
sphincter preserving rectal resection. MATERIAL AND METHODS: A total of 108
patients with a mid-to-low rectal cancer (UICC stage (y)0-III) who underwent
sphincter preserving surgery between January 2003 and October 2010 were
identified within the institutional prospective colorectal cancer database. The
impact of AL on 5-year overall (OS), cancer specific (CSS) and relapse-free
survival (RFS) was investigated. RESULTS: The overall leakage rate was 17.6 %
(grade A 4.6 %, grade B 4.6 % and grade C 8.3 %). After a median follow-up of 70
months (range 24-123 months), patients with an anastomotic leakage had a
significantly decreased 5-year OS (63.6 % versus 87.8 %, p = 0.02), CSS (72.2 %
versus 93.5 %, p = 0.02) and RFS rate (61.1 % versus 84.2 %, p = 0.01). In
univariable Cox regression analysis AL was associated with an unfavorable OS
(hazard ratio HR 3.05, 95 % CI: 1.11-8.39, p = 0.03), CSS (HR 4.21, 95 % CI: 1.13
15.70, p = 0.03) and RFS (HR 3.02, 95 % CI: 1.20-7.58, p = 0.02). CONCLUSION: In
the study cohort anastomotic leakage after sphincter preserving anterior
resection in patients with mid-to-low rectal cancer was associated with a
significantly unfavorable impact on overall and oncological survival.
PMID- 26428228
TI - [Laparoscopic liver resection for hepatocellular carcinoma].
PMID- 26428226
TI - iPSC-based drug screening for Huntington's disease.
AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder,
caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. The
disease generally manifests in middle age with both physical and mental symptoms.
There are no effective treatments or cures and death usually occurs 10-20 years
after initial symptoms. Since the original identification of the Huntington
disease associated gene, in 1993, a variety of models have been created and used
to advance our understanding of HD. The most recent advances have utilized stem
cell models derived from HD-patient induced pluripotent stem cells (iPSCs)
offering a variety of screening and model options that were not previously
available. The discovery and advancement of technology to make human iPSCs has
allowed for a more thorough characterization of human HD on a cellular and
developmental level. The interaction between the genome editing and the stem cell
fields promises to further expand the variety of HD cellular models available for
researchers. In this review, we will discuss the history of Huntington's disease
models, common screening assays, currently available models and future directions
for modeling HD using iPSCs-derived from HD patients. This article is part of a
Special Issue entitled SI: PSC and the brain.
PMID- 26428229
TI - [KRAS mutations and survival after resection of colorectal liver metastases].
PMID- 26428230
TI - Characteristics of Transmitted Drug-Resistant HIV-1 in Recently Infected
Treatment-Naive Patients in Japan.
AB - OBJECTIVES: Progress in antiretroviral treatment has led to fewer virological
failure cases, but 10%-20% of treatment-naive HIV/AIDS cases are reported to
harbor drug-resistant strains, suggesting transmission of drug-resistant HIV. We
aimed to determine the trend in prevalence of transmitted drug-resistant (TDR)
HIV in Japan, particularly in recently infected patients. METHODS: Drug
resistance test was performed on 3904 HIV-1-infected cases newly diagnosed
between 2007 and 2012. The number of cases infected within 6 months [recent
seroconverters (RS)] was estimated by BED assay of 2700 plasma samples.
Characteristics of RS cases were further analyzed. RESULTS: The overall
prevalence of TDR was 9.1%, ranging from 7.3% in 2008% to 12.5% in 2010. Among
1403 subtype B/E/D cases with >50 CD4 T cell counts and >1000 HIV copies per
milliliter, 468 (33.4%) were estimated to be RS. The prevalence of RS was
significantly higher among cases who were male, Japanese, and men who have sex
with men. The prevalence of TDR did not differ significantly between recent and
long-term seroconverters (8.5% vs. 9.2%, respectively, P = 0.68). Common
mutations in both groups were M46I/L and T215 revertants. Furthermore, sequences
with these mutations, K103N and D30N/N88D formed clusters on phylogenetic trees.
CONCLUSION: Our study clarified an increase in prevalence of TDR in Japan from
2007 to 2012. The phylogenetic clustering of cases with M46I/L or T215 revertants
suggests that HIV with these mutations have become circulating strains.
Furthermore, detailed analyses showed that Japanese men who have sex with men are
more aware of their risk of HIV infection.
PMID- 26428231
TI - Incorporating Acute HIV Screening into Routine HIV Testing at Sexually
Transmitted Infection Clinics, and HIV Testing and Counseling Centers in
Lilongwe, Malawi.
AB - BACKGROUND AND OBJECTIVES: Integrating acute HIV-infection (AHI) testing into
clinical settings is critical to prevent transmission, and realize potential
treatment-as-prevention benefits. We evaluated acceptability of AHI testing and
compared AHI prevalence at sexually transmitted infection (STI) clinics and HIV
testing and counseling (HTC) clinics in Lilongwe, Malawi. METHODS: We conducted
HIV RNA testing for HIV-seronegative patients visiting STI and HTC clinics. AHI
was defined as positive RNA and negative/discordant rapid antibody tests. We
evaluated demographic, behavioral, and transmission-risk differences between STI
and HTC patients and assessed performance of a risk-score for targeted screening.
RESULTS: Nearly two-thirds (62.8%, 9280/14,755) of eligible patients consented to
AHI testing. We identified 59 persons with AHI (prevalence = 0.64%)-a 0.9% case
identification increase. Prevalence was higher at STI [1.03% (44/4255)] than at
HTC clinics [0.3% (15/5025), P < 0.01], accounting for 2.3% of new diagnoses vs
0.3% at HTC clinic. Median viral load (VL) was 758,050 copies per milliliter; 25%
(15/59) had VL >= 10,000,000 copies per milliliter. Median VL was higher at STI
(1,000,000 copies/mL) compared with HTC (153,125 copies/mL, P = 0.2). Among
persons with AHI, those tested at STI clinics were more likely to report genital
sores compared with those tested at HTC clinics (54.6% vs 6.7%, P < 0.01). The
risk score algorithm performed well in identifying persons with AHI at HTC
clinics (sensitivity = 73%, specificity = 89%). CONCLUSIONS: The majority of
patients consented to AHI testing. AHI prevalence was substantially higher in STI
clinics than HTC clinics. Remarkably high VLs and concomitant genital scores
demonstrate the potential for transmission. Universal AHI screening at STI
clinics, and targeted screening at HTC centers, should be considered.
PMID- 26428232
TI - Constructing a synthetic constitutive metabolic pathway in Escherichia coli for
(R, R)-2,3-butanediol production.
AB - Many microorganisms could naturally produce (R, R)-2,3-butanediol ((R, R)-2,3
BD), which has unique applications due to its special chiral group and spatial
configuration. But the low enantio-purity of the product hindered the development
of large-scale production. In this work, a synthetic constitutive metabolic
pathway for enantiomerically pure (R, R)-2,3-BD biosynthesis was constructed in
Escherichia coli with vector pUC6S, which does not contain any lac sequences. The
expression of this artificial constructed gene cluster was optimized by using two
different strength of promoters (AlperPLTet01 (P01) and AlperBB (PBB)). The
strength of P01 is twice stronger than PBB. The fermentation results suggested
that the yield of (R, R)-2,3-BD was higher when using the stronger promoter.
Compared with the wild type, the recombinant strain E. coli YJ2 produced a small
amount of acetic acid and showed higher glucose consumption rate and higher cell
density, which indicated a protection against acetic acid inhibition. In order to
further increase the (R, R)-2,3-BD production by reducing the accumulation of its
precursor acetoin, the synthetic operon was reconstructed by adding the strong
promoter P01 in front of the gene ydjL coding for the enzyme of (R, R)-2,3-BD
dehydrogenase which catalyzes the conversion of acetoin to (R, R)-2,3-BD. The
engineered strain E. coli YJ3 showed a 20 % decrease in acetoin production
compared with that of E. coli YJ2. After optimization the fermentation
conditions, 30.5 g/L of (R, R)-2,3-BD and 3.2 g/L of acetoin were produced from
80 g/L of glucose within 18 h, with an enantio-purity over 99 %.
PMID- 26428233
TI - Bioaugmentation of anaerobic sludge digestion with iron-reducing bacteria:
process and microbial responses to variations in hydraulic retention time.
AB - Although anaerobic digestion (AD) is a widely used option to manage waste
activated sludge (WAS), there are some drawbacks related to its slow reaction
rate and low energy productivity. This study examined an anaerobic WAS digester,
augmented with an iron-reducing microbial consortium, relative to changes in
microbial community structure and process performance at decreasing hydraulic
retention times (HRTs) of 20 to 10 days. The enhanced methanation performance
(approximately 40 % increase in methane yield) by the bioaugmentation was
sustained until the HRT was decreased to 12.5 days, under Fe(3+)-rich conditions
(ferric oxyhydroxide, 20 mM Fe). Enhanced iron-reducing activity was evidenced by
the increased Fe(2+) to total Fe ratio maintained above 50 % during the stable
operational phases. A further decrease in HRT to 10 days resulted in a
significant performance deterioration, along with a drop in the Fe(2+) to total
Fe ratio to <35 %, after four turnovers of operation. Prevailing existence of
putative iron-reducing bacteria (IRBs) was identified by denaturing gradient gel
electrophoresis (DGGE), with Spirochaetaceae- and Thauera-related organisms being
dominant members, and clear dominance shifts among them with respect to decrease
in HRT were observed. Lowering HRT led to evident shifts in bacterial community
structure likely associated with washout of IRBs, leading to decreases in iron
respiration activity and AD performance at a lower HRT. The bacterial community
structure shifted dynamically over phases, and the community transitions
correlated well with the changes in process performance. Overall, the combined
biostimulation and bioaugmentation investigated in this study proved effective
for enhanced methane recovery from anaerobic WAS digestion, which suggests an
interesting potential for high-rate AD.
PMID- 26428234
TI - Mutagenesis of conserved active site residues of dihydrolipoamide
succinyltransferase enhances the accumulation of alpha-ketoglutarate in Yarrowia
lipolytica.
AB - alpha-Ketoglutarate (alpha-KG) is an important intermediate in the tricarboxylic
acid cycle and has broad applications. The mitochondrial ketoglutarate
dehydrogenase (KGDH) complex catalyzes the oxidation of alpha-KG to succinyl-CoA.
Disruption of KGDH, which may enhance the accumulation of alpha-KG theoretically,
was found to be lethal to obligate aerobic cells. In this study, individual
overexpression of dihydrolipoamide succinyltransferase (DLST), which serves as
the inner core of KGDH, decreased overall activity of the enzyme complex.
Furthermore, two conserved active site residues of DLST, His419, and Asp423 were
identified. In order to determine whether these residues are engaged in enzyme
reaction or not, these two conserved residues were individually mutated. Analysis
of the kinetic parameters of the enzyme variants provided evidence that the
catalytic reaction of DLST depended on residues His419 and Asp423. Overexpression
of mutated DLST not only impaired balanced assembly of KGDH, but also disrupted
the catalytic integrity of the enzyme complex. Replacement of the Asp423 residue
by glutamate increased extracellular alpha-KG by 40 % to 50 g L(-1) in mutant
strain. These observations uncovered catalytic roles of two conserved active site
residues of DLST and provided clues for effective metabolic strategies for
rational carbon flux control for the enhanced production of alpha-KG and related
bioproducts.
PMID- 26428235
TI - Targeting c-kit receptor in neuroblastomas and colorectal cancers using stem cell
factor (SCF)-based recombinant bacterial toxins.
AB - Autocrine activation of c-kit (KIT receptor tyrosine kinase) has been postulated
to be a potent oncogenic driver in small cell lung cancer, neuroblastoma (NB),
and poorly differentiated colorectal carcinoma (CRC). Although targeted therapy
involving tyrosine kinase inhibitors (TKIs) such as imatinib mesylate is highly
effective for gastrointestinal stromal tumor carrying V560G c-kit mutation, it
does not show much potential for targeting wild-type KIT (WT-KIT). Our study
demonstrates the role of stem cell factor (SCF)-based toxin conjugates for
targeting WT-KIT-overexpressing malignancies such as NBs and CRCs. We constructed
SCF-based recombinant bacterial toxins by genetically fusing mutated form of
natural ligand SCF to receptor binding deficient forms of Diphtheria toxin (DT)
or Pseudomonas exotoxin A (ETA') and evaluated their efficacy in vitro. Efficient
targeting was achieved in all receptor-positive neuroblastoma (IMR-32 and SHSY5Y)
and colon cancer cell lines (COLO 320DM, HCT 116, and DLD-1) but not in receptor
negative breast carcinoma cell line (MCF-7) thereby proving specificity. While
dose- and time-dependent cytotoxicity was observed in both neuroblastoma cell
lines, COLO 320DM and HCT 116 cells, only an anti-proliferative effect was
observed in DLD-1 cells. We prove that these novel targeting agents have
promising potential as KIT receptor tyrosine kinase targeting system.
PMID- 26428236
TI - Production of halophilic proteins using Haloferax volcanii H1895 in a stirred
tank bioreactor.
AB - The success of biotechnological processes is based on the availability of
efficient and highly specific biocatalysts, which can satisfy industrial demands.
Extreme and remote environments like the deep brine pools of the Red Sea
represent highly interesting habitats for the discovery of novel halophilic and
thermophilic enzymes. Haloferax volcanii constitutes a suitable expression system
for halophilic enzymes obtained from such brine pools. We developed a batch
process for the cultivation of H. volcanii H1895 in controlled stirred-tank
bioreactors utilising knockouts of components of the flagella assembly system.
The standard medium Hv-YPC was supplemented to reach a higher cell density.
Without protein expression, cell dry weight reaches 10 g L(-1). Two halophilic
alcohol dehydrogenases were expressed under the control of the tryptophanase
promoter p.tna with 16.8 and 3.2 mg gCDW (-1), respectively, at a maximum cell
dry weight of 6.5 g L(-1). Protein expression was induced by the addition of L
tryptophan. Investigation of various expression strategies leads to an optimised
two-step induction protocol introducing 6 mM L-tryptophan at an OD650 of 0.4
followed by incubation for 16 h and a second induction step with 3 mM L
tryptophan followed by a final incubation time of 4 h. Compared with the
uncontrolled shaker-flask cultivations used until date, dry cell mass
concentrations were improved by a factor of more than 5 and cell-specific enzyme
activities showed an up to 28-fold increased yield of the heterologous proteins.
PMID- 26428237
TI - Unveiling PHA-storing populations using molecular methods.
AB - Enrichment of mixed microbial cultures (MMCs) in polyhydroxyalkanoate (PHA)
storing microorganisms must take place to develop a successful PHA production
process. Moreover, throughout the operational period of a MMC system, the
population needs to be checked in order to understand the changes in the
performance that eventually occurred. For these reasons, it is necessary to
monitor the population evolution, in order to identify the different groups of
microorganisms and relate them with the storage capacity and kinetics of the MMC.
Regarding this particular process, several culture-independent molecular
techniques were already applied, with the use of hybridization techniques such
fluorescence in situ hybridization and also PCR-based methods like denaturing
gradient gel electrophoresis, terminal restriction fragment length polymorphism,
pyrosequencing, and quantitative PCR standing out. This review intends, thus, to
look at the molecular methods currently applied in monitoring the PHA-storing
population evolution and how they can be combined with the evolutionary
engineering step in order to optimize the overall process.
PMID- 26428238
TI - Biogas desulfurization using autotrophic denitrification process.
AB - The aim of this study was to evaluate the performance of an autotrophic
denitrification process for desulfurization of biogas produced from a chicken
manure digester. A laboratory scale upflow fixed bed reactor (UFBR) was operated
for 105 days and fed with sodium sulfide or H2S scrubbed from the biogas and
nitrate as electron donor and acceptor, respectively. The S/N ratio (2.5 mol/mol)
of the feed solution was kept constant throughout the study. When the UFBR was
fed with sodium sulfide solution with an influent pH of 7.7, about 95 % sulfide
and 90 % nitrate removal efficiencies were achieved. However, the inlet of the
UFBR was clogged several times due to the accumulation of biologically produced
elemental sulfur particles and the clogging resulted in operational problems.
When the UFBR was fed with the H2S absorbed from the biogas and operated with an
influent pH of 8-9, around 98 % sulfide and 97 % nitrate removal efficiencies
were obtained. In this way, above 95 % of the H2S in the biogas was removed as
elemental sulfur and the reactor effluent was reused as scrubbing liquid without
any clogging problem.
PMID- 26428239
TI - Trophic regulation of autoaggregation in Pseudomonas taiwanensis VLB120.
AB - Five mutants of Pseudomonas taiwanensis VLB120DeltaCeGFP showed significant
autoaggregation when growing on defined carbohydrates or gluconate, while they
grew as suspended cells on complex medium and on organic acids like citrate and
succinate. Surprisingly, the respective mutations affected very different genes,
although all five strains exhibited the same behaviour of aggregate formation. To
elucidate the mechanism of the aggregative behaviour, the microbial adhesion to
hydrocarbons (MATH) assay and contact angle measurements were performed that
pointed to an increased cell surface hydrophobicity. Moreover, investigations of
the outer layer of the cell membrane revealed a reduced amount of O-specific
polysaccharides in the lipopolysaccharide of the mutant cells. To determine the
regulation of the aggregation, reverse transcription quantitative real-time PCR
was performed and, irrespective of the mutation, the transcription of a gene
encoding a putative phosphodiesterase, which is degrading the global second
messenger cyclic diguanylate, was decreased or even deactivated in all mutants.
In summary, it appears that the trophic autoaggregation was regulated via cyclic
diguanylate and a link between the cellular cyclic diguanylate concentration and
the lipopolysaccharide composition of P. taiwanensis VLB120DeltaCeGFP is
suggested.
PMID- 26428240
TI - Enzymatic processing of protein-based fibers.
AB - Wool and silk are major protein fiber materials used by the textile industry.
Fiber protein structure-function relationships are briefly described here, and
the major enzymatic processing routes for textiles and other novel applications
are deeply reviewed. Fiber biomodification is described here with various classes
of enzymes such as protease, transglutaminase, tyrosinase, and laccase. It is
expected that the reader will get a perspective on the research done as a basis
for new applications in other areas such as cosmetics and pharma.
PMID- 26428241
TI - Contrasting microbial community composition and function perspective in sections
of a full-scale coking wastewater treatment system.
AB - To characterize the microbial community of the coking wastewater (CWW) treatment
system and to study the effects of CWW characteristics and operational parameters
on microbial communities, active sludge samples were collected from a full-scale
CWW treatment plant using three-phase fluidized bed biological reactors. High
throughput MiSeq sequencing was used to examine the 16S rRNA genes of
microbiology, revealing a distinct microbial composition among the active sludge
samples of three sequential bioreactors. Pseudomonas, Comamonas, and Thiobacillus
related sequences dominated in the anaerobic bioreactor A, aerobic bioreactor O1,
and aerobic bioreactor O2 active sludge with relative abundance of 72.59, 56.75,
and 27.82 %, respectively. The physico-chemical characteristics of CWW were
analyzed by standard methods and operational parameters were recorded to examine
their effects on the microbial communities. The redundancy analysis (RDA) results
showed that the bacterial communities of bioreactors A, O1, and O2 correlated
strongly with cyanides, phenols, and ammonia, respectively. These results expand
the knowledge about the biodiversity and population dynamics of microorganisms
and discerned the relationships between bacterial communities and environmental
variables in the biological treatment processes in the full-scale CWW treatment
system.
PMID- 26428242
TI - Tryptophan promotes morphological and physiological differentiation in
Streptomyces coelicolor.
AB - The molecular mechanisms regulating tryptophan biosynthesis in actinomycetes are
poorly understood; similarly, the possible roles of tryptophan in the
differentiation program of microorganism life-cycle are still underexplored. To
unveil the possible regulatory effect of this amino acid on gene expression, an
integrated study based on quantitative teverse transcription-PCR (qRT-PCR) and
proteomic approaches was performed on the actinomycete model Streptomyces
coelicolor. Comparative analyses on the microorganism growth in a minimal medium
with or without tryptophan supplementation showed that biosynthetic trp gene
expression in S. coelicolor is not subjected to a negative regulation by the
presence of the end product. Conversely, tryptophan specifically induces the
transcription of trp genes present in the biosynthetic gene cluster of the
calcium-dependent antibiotic (CDA), a lipopeptide containing D- and L-tryptophan
residues. In addition, tryptophan stimulates the transcription of the CDA gene
cluster regulator cdaR and, coherently, CDA production. Surprisingly, tryptophan
also promotes the production of actinorhodin, another antibiotic that does not
contain this amino acid in its structure. Combined 2D-DIGE and nano liquid
chromatography electrospray linear ion trap tandem mass spectrometry (LC-ESI-LIT
MS/MS) analyses revealed that tryptophan exerts a growth-stage-dependent global
effect on S. coelicolor proteome, stimulating anabolic pathways and promoting the
accumulation of key factors associated with morphological and physiological
differentiation at the late growth stages. Phenotypic observations by scanning
electron microscopy and spore production assays demonstrated an increased
sporulation in the presence of tryptophan. Transcriptional analysis of catabolic
genes kynA and kynB suggested that the actinomycete also uses tryptophan as a
carbon and nitrogen source. In conclusion, this study originally provides the
molecular basis underlying the stimulatory effect of tryptophan on the production
of antibiotics and morphological development program of this actinomycete.
PMID- 26428243
TI - Characterization of a unique Caulobacter crescentus aldose-aldose oxidoreductase
having dual activities.
AB - We describe here the characterization of a novel enzyme called aldose-aldose
oxidoreductase (Cc AAOR; EC 1.1.99) from Caulobacter crescentus. The Cc AAOR
exists in solution as a dimer, belongs to the Gfo/Idh/MocA family and shows
homology with the glucose-fructose oxidoreductase from Zymomonas mobilis.
However, unlike other known members of this protein family, Cc AAOR is specific
for aldose sugars and can be in the same catalytic cycle both oxidise and reduce
a panel of monosaccharides at the C1 position, producing in each case the
corresponding aldonolactone and alditol, respectively. Cc AAOR contains a tightly
bound nicotinamide cofactor, which is regenerated in this oxidation-reduction
cycle. The highest oxidation activity was detected on D-glucose but significant
activity was also observed on D-xylose, L-arabinose and D-galactose, revealing
that both hexose and pentose sugars are accepted as substrates by Cc AAOR. The
configuration at the C2 and C3 positions of the saccharides was shown to be
especially important for the substrate binding. Interestingly, besides
monosaccharides, Cc AAOR can also oxidise a range of 1,4-linked oligosaccharides
having aldose unit at the reducing end, such as lactose, malto- and cello
oligosaccharides as well as xylotetraose. (1)H NMR used to monitor the oxidation
and reduction reaction simultaneously, demonstrated that although D-glucose has
the highest affinity and is also oxidised most efficiently by Cc AAOR, the
reduction of D-glucose is clearly not as efficient. For the overall reaction
catalysed by Cc AAOR, the L-arabinose, D-xylose and D-galactose were the most
potent substrates.
PMID- 26428244
TI - Inoculum pre-treatment affects the fermentative activity of hydrogen-producing
communities in the presence of 5-hydroxymethylfurfural.
AB - To enhance the productivity of mixed microbial cultures for fermentative bio
hydrogen production, chemical-physical pre-treatments of the original seed are
needed to suppress the activity of hydrogen (H2)-consuming microbes. This
approach might influence negatively the composition and diversity of the hydrogen
producing community with consequences on the functional stability of the H2
producing systems in case of perturbations. In this study, we aimed at
investigating the effect of different types of pre-treatment on the performance
of hydrogen production systems in the presence of an inhibitor, such as 5
hydroxymethylfurfural (HMF). The efficiency and the microbial community structure
of batch reactors amended with HMF and inoculated with non-pretreated and
pretreated (acid, heat shock, and aeration) anaerobic sludge were evaluated and
compared with control systems. The type of pre-treatments influenced the
microbial community assembly and activity in inhibited systems, with significant
effect on the performance. Cumulative H2 production tests showed that the pre
aerated systems (control and HMF inhibited) were the most efficient, while the
difference of the lag phase of the pre-acidified control and HMF-added test was
negligible. Analyses of the structure of the enriched microbial community in the
systems through PCR-denaturing gradient gel electrophoresis (DGGE) followed by
band sequencing revealed that the differences in performance were mostly related
to shifts in the metabolic pathways rather than in the predominant species. In
conclusion, the findings suggest that the use of specific inoculum pre-treatment
could contribute to regulate the metabolic activity of the fermentative H2
producing bacteria in order to enhance the bio-energy production.
PMID- 26428245
TI - Receptor Dissociation and B-Cell Activation.
AB - The B-cell antigen receptor (BCR) is one of the most abundant receptors on the
surface of B cells with roughly 100,000-200,000 copies per cell. Signaling
through the BCR is crucial for the activation and differentiation of B cells.
Unlike other receptors, the BCR can be activated by a large set of structurally
different ligands, but the molecular mechanism of BCR activation is still a
matter of controversy. Although dominant for a long time, the cross-link model
(CLM) of BCR activation is not supported by recent studies of the nanoscale
organization of the BCR on the surface of resting B cells. In contrast to the
prediction of CLM, the numerous BCR complexes on these cells are not randomly
distributed monomers but rather form oligomers which reside within membrane
confinements. This finding is more in line with the dissociation activation model
(DAM), wherein B-cell activation is accompanied by an opening of the auto
inhibited BCR oligomers instead of a cross-linking of the BCR monomers. In this
review, we discuss in detail the new findings and their implications for BCR
signaling.
PMID- 26428246
TI - Penetration of Treosulfan and its Active Monoepoxide Transformation Product into
Central Nervous System of Juvenile and Young Adult Rats.
AB - Treosulfan (TREO) is currently investigated as an alternative treatment of
busulfan in conditioning before hematopoietic stem cell transplantation. The
knowledge of the blood-brain barrier penetration of the drug is still scarce. In
this paper, penetration of TREO and its active monoepoxide (S,S-EBDM) and
diepoxide (S,S-DEB) into the CNS was studied in juvenile (JR) and young adult
rats (YAR) for the first time. CD rats of both sexes (n = 96) received an
intravenous dose of TREO 500 mg/kg b.wt. Concentrations of TREO, S,S-EBDM, and
S,S-DEB in rat plasma, brain, and cerebrospinal fluid (CSF, in YAR only) were
determined by validated bioanalytical methods. Pharmacokinetic calculations were
performed in WinNonlin using a noncompartmental analysis and statistical
evaluation was done in Statistica software. In male JR, female JR, male YAR, and
female YAR, the brain/plasma area under the curve (AUC) ratio for unbound TREO
was 0.14, 0.17, 0.10, and 0.07 and for unbound S,S-EBDM, it was 0.52, 0.48, 0.28,
and 0.22, respectively. The CSF/plasma AUC ratio in male and female YAR was 0.12
and 0.11 for TREO and 0.66 and 0.64 for S,S-EBDM, respectively. Elimination rate
constants of TREO and S,S-EBDM in all the matrices were sex-independent with a
tendency to be lower in the JR. No quantifiable levels of S,S-DEB were found in
the studied samples. TREO and S,S-EBDM demonstrated poor and sex-independent
penetration into CNS. However, the brain exposure was greater in juvenile rats,
so very young children might potentially be more susceptible to high-dose TREO
related CNS exposure than young adults.
PMID- 26428247
TI - Two-component regulatory systems: The moment of truth.
PMID- 26428248
TI - The Tunisian oasis ecosystem is a source of antagonistic Bacillus spp. producing
diverse antifungal lipopeptides.
AB - The use of microbial products has become a promising alternative approach to
controlling plant diseases caused by phytopathogenic fungi. Bacteria isolated
from the date palm tree rhizosphere of the Tunisian oasis ecosystem could provide
new biocontrol microorganisms adapted to extreme conditions, such as drought,
salinity and high temperature. The aim of this study was to screen bacteria
isolated from the rhizosphere of the date palm tree for their ability to inhibit
phytopathogenic fungi, and to identify molecules responsible for their antifungal
activity. Screening for antifungal activity was performed on twenty-eight
isolates. Five antagonistic isolates were selected and identified as different
species of Bacillus using phenotypical methods and a molecular approach. The five
antagonistic Bacillus isolated showed tolerance to abiotic stresses (high
temperature, salinity, drought). Their ability to produce lipopeptides was
investigated using a combination of two techniques: PCR amplification and MALDI
ToF mass spectrometry. Analyses revealed that the antagonistic isolates produced
a high diversity of lipopeptides that belonged to surfactin, fengycin, iturin and
kurstakin families. Their antagonistic activity, related to their capacity for
producing diverse antifungal lipopeptides and their tolerance to abiotic
stresses, highlighted Bacillus strains isolated from the rhizosphere of the date
palm tree as potential biocontrol agents for combatting plant diseases in extreme
environments.
PMID- 26428249
TI - Long-term Safety and Efficacy of Tapentadol Extended Release Following up to 2
Years of Treatment in Patients With Moderate to Severe, Chronic Pain: Results of
an Open-label Extension Trial.
AB - PURPOSE: Tapentadol extended release (ER) has demonstrated efficacy and safety
for the management of moderate to severe, chronic pain in adults. This study
evaluated the long-term safety and tolerability of tapentadol ER in patients with
chronic osteoarthritis or low back pain. METHODS: Patients were enrolled in this
1-year, open-label extension study after completing one of two 15-week, placebo
controlled studies of tapentadol ER and oxycodone controlled release (CR) for
osteoarthritis knee pain (NCT00421928) or low back pain (NCT00449176), a 7-week
crossover study between tapentadol immediate release and tapentadol ER for low
back pain (NCT00594516), or a 1-year safety study of tapentadol ER and oxycodone
CR for osteoarthritis or low back pain (NCT00361504). After titrating the drug to
an optimal dose, patients received tapentadol ER (100-250 mg BID) for up to 1
year (after finishing treatment in the preceding studies); patients who were
previously treated with tapentadol ER in the 1-year safety study received
tapentadol ER continuously for up to 2 years in total. FINDINGS: Of the 1,154
patients in the safety population, 82.7% were aged >65 years and 57.9% were
female; 50.1% had mild baseline pain intensity. Mean (SD) pain intensity scores
(11-point numerical rating scale) were 3.9 (2.38) at baseline (end of preceding
study) and 3.7 (2.42) at end point, indicating that pain relief was maintained
during the extension study. Improvements in measures of quality of life (eg,
EuroQol-5 Dimension and the 36-item Short Form Health Survey [SF-36]) health
status questionnaires) achieved during the preceding studies were maintained
during the open-label extension study. Tapentadol ER was associated with a safety
and tolerability profile comparable to that observed in the preceding studies.
The most common treatment-emergent adverse events (incidence >=10%; n = 1154)
were headache (13.1%), nausea (11.8%), and constipation (11.1%). Similar efficacy
and tolerability results were shown for patients who received up to 2 years of
tapentadol ER treatment. IMPLICATIONS: Pain relief and improvements in quality of
life achieved during the preceding studies were maintained throughout this
extension study, during which tapentadol ER was well tolerated for the long-term
treatment of chronic osteoarthritis or low back pain over up to 2 years of
treatment. (ClinicalTrials.gov identifier: NCT00487435.).
PMID- 26428250
TI - Gastroesophageal Reflux Disease and Sleeve Gastrectomy.
AB - Gastroesophageal reflux disease (GERD) and/or hiatus hernia (HH) are one of the
most common disorders of the upper gastrointestinal tract. Despite the positive
effect of sleeve gastrectomy (SG) regarding weight loss and improvement in
obesity co-morbidities, there are concerns about the development of de novo
gastroesophageal reflux disease or worsening the existing GERD after this
bariatric operation. Furthermore, controversy exists on the consequences of SG in
lower esophageal sphincter function and about the ideal procedure when a hiatus
hernia is preoperatively diagnosed or discovered during the laparoscopic SG. This
review systematically investigates the incidence, the pathophysiology of GERD
and/or HH in morbidly obese individuals before and after SG, and the treatment
options for concomitant HH repair during laparoscopic sleeve gastrectomy.
PMID- 26428251
TI - Early Weight Loss as a Predictor of 2-Year Weight Loss and Resolution of
Comorbidities After Sleeve Gastrectomy.
AB - BACKGROUND: The objective of this study was to investigate whether early
postoperative weight loss predicts weight loss 1 and 2 years after laparoscopic
sleeve gastrectomy (LSG) and to determine its effect on the resolution of
comorbidities. METHODS: This was a prospective study of patients who underwent
LSG at Jordan University Hospital from February 2009 to January 2014. RESULTS:
One hundred ninety patients (mean age 34.0 +/- 10.8 years; mean preoperative body
mass index 46.2 +/- 7.7 kg/m(2)) were included in the study. Of these, 146 were
followed for 1 year and 73 were followed for 2 years. Thirty patients (20.5 %)
had hypertension, 23 (15.8 %) had diabetes, 78 (53.4 %) had hyperlipidemia, 30
(20.5 %) had obstructive sleep apnea, and 50 (34.2 %) had more than one
comorbidity. The percentage of excess weight loss (%EWL) was 22.7 +/- 8.1, 75.1
+/- 22.8, and 72.6 +/- 17.5 at 1, 12, and 24 months, respectively. Fifty-five
patients (37.7 %) had a 1-year %EWL of >=80 %, and 29 (39.7 %) had a 2-year %EWL
of >=80 %. Linear regression analysis showed a strong correlation between 1-month
%EWL and %EWL at 1 year (r (2) = 0.23, p < 0.001) and 2 years (r (2) = 0.28, p <
0.001). Resolution of comorbidities was associated with higher %EWL achieved at 1
year, but early postoperative weight loss did not have a significant effect on
comorbidity resolution. CONCLUSIONS: Early postoperative weight loss can be used
to identify and target poor responders.
PMID- 26428252
TI - Association Between Bariatric Surgery and Bone Metabolism.
PMID- 26428253
TI - Marriage and Weight Loss Surgery: a Narrative Review of Patient and Spousal
Outcomes.
AB - Long-term weight maintenance following weight loss surgery (WLS) may be
challenging for patients without supportive spouses. The health behaviors and
relationship quality of spouses pre- and post-WLS have rarely been explored,
leaving providers with little guidance on how to engage spouses in treatment. The
purpose of this review is to synthesize the empirical research on relationship
factors and WLS among married couples. The identified articles (N = 13) reported
that the amount of weight lost post-WLS tended to be lower for married patients,
couples' relationship quality tended to decline from pre- to post-WLS, and sexual
contact increased post-WLS. Future research should explore how the relationship
factors and quality of couples may influence patients' WLS outcomes over time to
identify ways that interventions can enhance the couple's relationship and
health.
PMID- 26428254
TI - Routine Liver Biopsy During Bariatric Surgery: an Analysis of Evidence Base.
AB - Non-alcoholic fatty liver disease and non-alcoholic steato-hepatitis are common
in patients undergoing bariatric surgery. Non-alcoholic steato-hepatitis can
progress to cirrhosis of the liver and hepatocellular carcinoma. Non-invasive
methods of diagnosing non-alcoholic steato-hepatitis are not as accurate as liver
biopsy, and bariatric surgery presents a unique opportunity to carry out a
simultaneous liver biopsy. Routine liver biopsy can help early and accurate
diagnosis of obesity-associated liver conditions. This has led some surgeons to
argue for routine liver biopsy at the time of bariatric surgery. However, most
bariatric surgeons remain unconvinced and liver biopsy is currently not routine
practice with bariatric surgery. This review examines published scientific
literature to ascertain the usefulness of routine liver biopsy at the time of
bariatric surgery.
PMID- 26428255
TI - Wolbachia spread dynamics in stochastic environments.
AB - Dengue fever is a mosquito-borne viral disease with 100 million people infected
annually. A novel strategy for dengue control uses the bacterium Wolbachia to
invade dengue vector Aedes mosquitoes. As the impact of environmental
heterogeneity on Wolbachia spread dynamics in natural areas has been rarely
quantified, we develop a model of differential equations for which the
environmental conditions switch randomly between two regimes. We find some
striking phenomena that random regime transitions could drive Wolbachia to
extinction from certain initial states confirmed Wolbachia fixation in
homogeneous environments, and mosquito releasing facilitates Wolbachia invasion
more effectively when the regimes transit frequently. By superimposing the phase
spaces of the ODE systems defined in each regime, we identify the threshold
curves below which Wolbachia invades the whole population, which extends the
theory of threshold infection frequency to stochastic environments.
PMID- 26428257
TI - Modeling spatial trajectories in dynamics testing using basis splines:
application to tracking human volunteers in low-speed frontal impacts.
AB - Designing motor vehicle safety systems requires knowledge of whole body
kinematics during dynamic loading for occupants of varying size and age, often
obtained from sled tests with postmortem human subjects and human volunteers.
Recently, we reported pediatric and adult responses in low-speed (<4 g)
automotive-like impacts, noting reductions in maximum excursion with increasing
age. Since the time-based trajectory shape is also relevant for restraint design,
this study quantified the time-series trajectories using basis splines and
developed a statistical model for predicting trajectories as a function of body
dimension or age. Previously collected trajectories of the head, spine, and
pelvis were modeled using cubic basis splines with eight control points. A
principal component analysis was conducted on the control points and related to
erect seated height using a linear regression model. The resulting statistical
model quantified how trajectories became shorter and flatter with increasing body
size, corresponding to the validation data-set. Trajectories were then predicted
for erect seated heights corresponding to pediatric and adult anthropomorphic
test devices (ATDs), thus generating performance criteria for the ATDs based on
human response. This statistical model can be used to predict trajectories for a
subject of specified anthropometry and utilized in subject-specific computational
models of occupant response.
PMID- 26428258
TI - A flavonoid compound from Chrysosplenium nudicaule inhibits growth and induces
apoptosis of the human stomach cancer cell line SGC-7901.
AB - CONTEXT: Gastric cancer remains highly prevalent, but treatment options are
limited. Natural products have proved to be a rich source of anticancer drugs.
Chrysosplenium nudicaule Ledeb. (Saxifragaceae) is a perennial herb that grows in
the highlands of China. It has been used as a traditional Chinese medicine to
treat digestive diseases for hundreds of years. Recent studies revealed that this
herb had anticancer activity, and the flavonoids were speculated to be the
effective components. 6,7,3'-Trimethoxy-3,5,4'-trihydroxy flavone (TTF) and 5,4'
dihydroxy-3,6,3'trimethoxy-flavone-7-O-beta-d-glucoside (DTFG) are flavonoid
compounds isolated from Chrysosplenium nudicaule. OBJECTIVE: This study examined
the effect of TTF and DTFG on SGC-7901 human stomach cancer cell in vitro to
determine the anticancer and induction of apoptosis properties of TTF. MATERIALS
AND METHODS: The proliferation of cells treated with 32, 16, 8, 4, and 2 MUg/mL
of TTF or DTFG for 24, 48, and 72 h was assessed by the MTT assay. After being
treated with TTF, the apoptosis of SGC-7901 cells was assessed by acridine orange
staining, ultrastructure, electrophoresis of DNA fragmentation, and flow
cytometry. RESULTS: Results indicated that TTF inhibited the growth of cancer
cells with an IC50 value of 8.33 MUg/mL after 72 h incubation. However, DTFG
showed no inhibitory effect on the growth of the cancer cell. Further studies on
TTF also confirmed that it was able to induce apoptosis of SGC-7901 cells at a
concentration as low as 4 MUg/mL. DISCUSSION AND CONCLUSION: The apoptotic effect
of TTF makes it a promising candidate for future chemotherapeutic application in
treating stomach cancer.
PMID- 26428259
TI - ZnO/CoO and ZnCo2O4 Hierarchical Bipyramid Nanoframes: Morphology Control,
Formation Mechanism, and Their Lithium Storage Properties.
AB - Mastery over the structure of nanoscale materials can effectively tailor and
regulate their electrochemical properties, enabling improvement in both rate
capability and cycling stability. We report the shape-controlled synthesis of
novel mesoporous bicomponent-active ZnO/CoO hierarchical multilayered bipyramid
nanoframes (HMBNFs). The as-synthesized micro/nanocrystals look like multilayered
bipyramids and consist of a series of structural units with similar frames and
uniform sheet branches. The use of an appropriate straight-chain monoalcohol was
observed to be critical for the formation of HMBNFs. In addition, the structure
of HMBNFs could be preserved only in a limited range of the precursor ratio. An
extremely fast crystal growth process and an unusual transverse crystallization
of the ZnCo-carbonate HMBNFs were newly discovered and proposed. By calcination
of ZnCo-carbonate HMBNFs at the atmosphere of nitrogen and air, ZnO/CoO and
ZnCo2O4 HMBNFs were obtained, respectively. Compared to the ZnCo2O4 HMBNFs, the
ZnO/CoO HMBNFs with a uniform distribution of nanocrystal ZnO and CoO subunits
exhibited enhanced electrochemical activity, including greater rate capability
and longer cycling performance, when evaluated as an anode material for Li-ion
batteries. The superior electrochemical performance of the ZnO/CoO HMBNFs is
attributed to the unique nanostructure, bicomponent active synergy, and uniform
distribution of ZnO and CoO phases at the nanoscale.
PMID- 26428260
TI - Is the fibrotic parietal thickening a reliable parameter for diagnosing previous
asymptomatic deep vein thrombosis?
AB - AIM: Research of a starting point to debate about the possibility of identifying
a unique sign of previous DVT. MATERIAL OF STUDY: A retrospective study involving
202 outpatients with venous insufficiency of the lower limbs (CEAP classes C
4/6), classified according to the affected venous district. Patients positive for
deep vein thrombosis (DVT) were subjected to Compression Ultra Sound test (CUS
test) with measurement of the wall thickness at the point of formation of the
thrombus and at fixed points of common femoral and popliteal veins used also in
the patients with negative history of DVT RESULTS: Among total group, only 19
patients (9.40%) had an history of DVT. No one of them had a superficial
incontinence. The measurement of wall thickness in positive DVT history patients
(group A) resulted in an average value of 1.10 mm (s.d=0.06), while the average
value obtained in negative DVT history (group B) was 0.55 mm (s.d.= 0.20).
However, in 13 patients wall thickness was > 1mm (mean: 1.04 mm). The difference
between the averages of group A and B was statistically significant (p <0.05).
DISCUSSION: In all positive DVT history patients and in 13 ones with negative
history we found an increase in wall thickness, with a value > 1 mm. Can the wall
thickening more than 1 mm be considered an indicator of previous DVT? Can it be
considered a "marker" for thrombophilia status? CONCLUSIONS: The usefulness of a
sign of previous DVT (even if asymptomatic), detected during a routine Doppler
ultrasound check of lower limbs, could be a warning bell to investigate
thrombophilia status. KEY WORDS: Chronic Venous Insufficiency, Duplex ultrasound,
Hypercoagulability, Post-thrombotic Syndrome, Venous Thromboembolism.
PMID- 26428261
TI - Zoonotic transmission of rotavirus: surveillance and control.
AB - Group A rotavirus (Rotavirus A, RVA) is the main cause of acute dehydrating
diarrhea in humans and numerous animal species. RVA shows vast diversity and a
variety of human strains share genetic and antigenic features with animal origin
RVA strains. This finding suggests that interspecies transmission is an important
mechanism of rotavirus evolution and contributes to the diversity of human RVA
strains. RVA is responsible for half a million deaths and several million
hospitalizations worldwide. Globally, two rotavirus vaccines are available for
routine use in infants. These vaccines show a great efficacy profile and induce
protective immunity against various rotavirus strains. However, little is known
about the long-term evolution and epidemiology of RVA strains under selective
pressure related to vaccine use. Continuous strain surveillance in the post
vaccine licensure era is needed to help better understand mechanisms that may
affect vaccine effectiveness.
PMID- 26428262
TI - The application of human phase 0 microdosing trials: A systematic review and
perspectives.
AB - A decreasing number of new therapeutic drugs reaching the clinic has led to the
publication of regulatory guidelines on human microdosing trials by the European
Medicines Agency in 2004 and the US Food and Drug Administration in 2006.
Microdosing trials are defined by the administration of 1/100th of the
therapeutic dose and designed to investigate basic drug properties. This review
investigates the current application of phase 0 trials in medical research.
Thirty-three studies found in PubMed and EMBASE were systematically reviewed for
aim and analytical method. Pharmacokinetic studies have been a major focus of
phase 0 trials, but drug distribution, drug-drug interactions, imaging and
pharmacogenomics have also been investigated. Common analytical methods were
tandem mass liquid chromatography, accelerator mass spectrometry and positron
emission tomography. New ongoing trials are investigating the pharmacodynamics
and chemoresistance of marketed drugs, suggesting that the application of phase 0
trials is still evolving.
PMID- 26428267
TI - Inhaled sildenafil nanocomposites: lung accumulation and pulmonary
pharmacokinetics.
AB - CONTEXT: Administration of sildenafil citrate (SC) is considered as a strategy in
the treatment of pulmonary hypertension. OBJECTIVE: This study reports production
of the inhalable microparticles containing SC-loaded poly(lactide-co-glycolic
acid)-nanoparticles. METHODS: SC-nanoparticles were prepared by the double
emulsion solvent evaporation method. Next, free SC and SC-loaded nanoparticles
were spray dried in the presence of appropriate excipients (lactose, maltose and
trehalose). Physicochemical properties and aerodynamic behavior of prepared
powders were evaluated. In addition, drug accumulation from selected formulations
in the rat lung tissue was compared with oral and IV administration. RESULTS:
Size and fine particle fraction of selected nanocomposites and free SC
microparticles were 7 and 4.5 um, and 60.2% and 68.2%, respectively. Following
oral and IV administration, the drug was not detectable in the lung after 4 and 6
h, respectively, but in SC-loaded nanoparticles, the drug was detectable in the
lung even after 12 h of inhalation. Respirable particles containing free SC
provided high concentration at first that was detectable up to 6 after
insufflation. CONCLUSION: In vivo study demonstrated that pulmonary
administration of sildenafil and sildenafil nanoparticles produced longer half
life and higher concentration of the drug in the lung tissue as compared to oral
and IV administration. So, these formulations could be more effective than oral
and IV administration of this drug.
PMID- 26428268
TI - Emergence of new virulent populations of apple scab from nonagricultural disease
reservoirs.
AB - Plant pathogens adapt readily to new crop varieties in agrosystems, and it is
crucial to understand the factors underlying the epidemic spread of new virulent
strains if we are to develop more efficient strategies to control them. In this
study we used multilocus microsatellite typing, molecular epidemiology tools and
a large collection of isolates from cultivated, wild and ornamental apples to
investigate the origin of new virulent populations of Venturia inaequalis, an
ascomycete fungus causing apple scab on varieties carrying the Rvi6 resistance
gene. We demonstrated a common origin at the European scale of populations
infecting apples (Malus * domestica) carrying the Rvi6 resistance and Malus
floribunda, the progenitor of the Rvi6 resistance. Demographic modeling indicated
that the Rvi6-virulent lineage separated several thousands of years ago from
populations infecting non-Rvi6 hosts, without detectable gene flow between the
two lineages. These findings show that 'breakdowns' of plant resistance genes can
be caused by the selection and migration of virulent genotypes from standing
genetic variation maintained in environmental disease reservoirs, here ornamental
crabapples. This work stresses the need to take better account of pathogen
diversity in resistance screenings of breeding lines and in resistance deployment
strategies, in order to enhance sustainable disease management.
PMID- 26428269
TI - Quality of life among patients with rosacea: an investigation of patients in
China using two structured questionnaires.
PMID- 26428271
TI - Cytotoxicity, Antioxidant and Apoptosis Studies of Quercetin-3-O Glucoside and 4
(beta-D-Glucopyranosyl-1->4-alpha-L-Rhamnopyranosyloxy)-Benzyl Isothiocyanate
from Moringa oleifera.
AB - Moringa oleifera, from the family Moringaceae, is used as a source of vegetable
and herbal medicine and in the treatment of various cancers in many African
countries, including Kenya. The present study involved the phytochemical analyses
of the crude extracts of M.oleifera and biological activities (antioxidant,
cytotoxicity and induction of apoptosis in-vitro) of selected isolated compounds.
The compounds isolated from the leaves and seeds of the plant were quercetin-3-O
glucoside (1), 4-(beta-D-glucopyranosyl-1->4-alpha-L-rhamnopyranosyloxy)-benzyl
isothiocyanate (2), lutein (3), and sitosterol (4). Antioxidant activity of
compound 1 was significant when compared to that of the control, while compound 2
showed moderate activity. The cytotoxicity of compounds 1 and 2 were tested in
three cell lines, viz. liver hepatocellular carcinoma (HepG2), colon carcinoma
(Caco-2) and a non-cancer cell line Human Embryonic Kidney (HEK293), using the
MTT cell viability assay and compared against a standard anticancer drug, 5
fluorouracil. Apoptosis studies were carried out using the acridine
orange/ethidium bromide dual staining method. The isolated compounds showed
selective in vitro cytotoxic and apoptotic activity against human cancer and non
cancer cell lines, respectively. Compound 1 showed significant cytotoxicity
against the Caco-2 cell line with an IC50 of 79 MUg mL(-1) and moderate
cytotoxicity against the HepG2 cell line with an IC50 of 150 MUg mL(-1), while
compound 2 showed significant cytotoxicity against the Caco- 2 and HepG2 cell
lines with an IC50 of 45 MUg mL(-1) and 60 MUg mL(-1), respectively.
Comparatively both compounds showed much lower cytotoxicity against the HEK293
cell line with IC50 values of 186 MUg mL(-1) and 224 MUg mL(-1), respectively.
PMID- 26428272
TI - Chemoselective Alkene Hydrosilylation Catalyzed by Nickel Pincer Complexes.
AB - Chemoselective hydrosilylation of functionalized alkenes is difficult to achieve
using base-metal catalysts. Reported herein is that well-defined bis(amino)amide
nickel pincer complexes are efficient catalysts for anti-Markovnikov
hydrosilylation of terminal alkenes with turnover frequencies of up to 83,000 per
hour and turnover numbers of up to 10,000. Alkenes containing amino, ester,
amido, ketone, and formyl groups are selectively hydrosilylated. A slight
modification of reaction conditions allows tandem isomerization/hydrosilylation
reactions of internal alkenes using these nickel catalysts.
PMID- 26428273
TI - Identification of a characteristic antioxidant, anthrasesamone F, in black sesame
seeds and its accumulation at different seed developmental stages.
AB - Assay-guided fractionation of the methanol extract from black seeds of sesame
(Sesamum indicum L.) led to the isolation of an active compound that had a 1,1
diphenyl-2-picrylhydrazyl radical scavenging activity. This antioxidant was
confirmed to be anthrasesamone F, an anthraquinone derivative previously isolated
from different black sesame seeds and biogenetically related to other
anthrasesamones in sesame roots. The radical scavenging assay showed that
anthrasesamone F had more potent activity than Trolox. The content of
anthrasesamone F in different parts and at different developmental stages of
black sesame seeds was investigated to clarify the accumulation pattern of this
antioxidant in the black seeds. Anthrasesamone F was localized in the seed coat
of black seeds and accumulated after the seed coat color changed to black. The
content of anthrasesamone F increased gradually with seed maturation and
drastically on air-drying, the final stage in sesame cultivation.
PMID- 26428274
TI - A Longitudinal (6-week) 3T (1)H-MRS Study on the Effects of Lithium Treatment on
Anterior Cingulate Cortex Metabolites in Bipolar Depression.
AB - The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no
longitudinal study has specifically evaluated lithium's effects on ACC
metabolites using (1)H-MRS, as well as its association with clinical improvement
in bipolar depression. This (1)H-MRS (TE=35ms) study evaluated 24 drug-free BD
patients during depressive episodes and after lithium treatment at therapeutic
levels. Brain metabolite levels (N-acetyl aspartate (NAA), creatine (tCr),
choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline
(week 0) and after lithium monotherapy (week 6). The present investigation showed
that ACC glutamate (Glu/tCr) and glutamate+glutamine (Glx/tCr) significantly
increased after six weeks of lithium therapy. Regarding the association with
clinical improvement, remitters showed an increase in myoinositol levels (mI/tCr)
after lithium treatment compared to non-remitters. The present findings reinforce
a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets
for lithium's therapeutic effects in BD.
PMID- 26428275
TI - Facile Synthesis of Trisubstituted Carbazoles by Acid-Catalyzed Ring-Opening
Annulation of 2-Amidodihydrofurans with Indoles.
AB - A mild and convenient synthesis of carbazoles by TfOTMS (trimethylsilyl
trifluoromethanesulfonate)-catalyzed ring-opening annulation of 2
amidodihydrofurans is presented with a high degree of chemoselectivity and
regioselectivity. This procedure was also scaled up to a gram-scale synthesis.
The reaction could involve an iminonium intermediate through a series of C-O, C-N
bond cleavages, C-C bond formations, and a 1,2-migration process.
PMID- 26428276
TI - Differences in gluten metabolism among healthy volunteers, coeliac disease
patients and first-degree relatives.
AB - Coeliac disease (CD) is an immune-mediated enteropathy resulting from exposure to
gluten in genetically predisposed individuals. Gluten proteins are partially
digested by human proteases generating immunogenic peptides that cause
inflammation in patients carrying HLA-DQ2 and DQ8 genes. Although intestinal
dysbiosis has been associated with patients with CD, bacterial metabolism of
gluten has not been studied in depth thus far. The aim of this study was to
analyse the metabolic activity of intestinal bacteria associated with gluten
intake in healthy individuals, CD patients and first-degree relatives of CD
patients. Faecal samples belonging to twenty-two untreated CD patients, twenty
treated CD patients, sixteen healthy volunteers on normal diet, eleven healthy
volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on
normal diet and sixty-nine relatives on GFD were tested for several proteolytic
activities, cultivable bacteria involved in gluten metabolism, SCFA and the
amount of gluten in faeces. We detected faecal peptidasic activity against the
gluten-derived peptide 33-mer. CD patients showed differences in faecal
glutenasic activity (FGA), faecal tryptic activity (FTA), SCFA and faecal gluten
content with respect to healthy volunteers. Alterations in specific bacterial
groups metabolising gluten such as Clostridium or Lactobacillus were reported in
CD patients. Relatives showed similar parameters to CD patients (SCFA) and
healthy volunteers (FTA and FGA). Our data support the fact that commensal
microbial activity is an important factor in the metabolism of gluten proteins
and that this activity is altered in CD patients.
PMID- 26428279
TI - Synthesis of magnetic mesoporous titania colloidal crystals through evaporation
induced self-assembly in emulsion as effective and recyclable photocatalysts.
AB - This study illustrates the directed self-assembly of mesoporous TiO2 with
magnetic properties due to its colloidal crystal structure with Fe3O4. The Fe3O4
nanoparticles were synthesized using co-precipitation techniques to a size of
28.2 nm and a magnetic saturation of 66.9 emu g(-1). Meanwhile, mesoporous
titania nanoparticles (MTNs) with a particle diameter of 373 nm, a specific
surface area of 236.3 m(2) g(-1), and a pore size of 2.8 nm were prepared by
controlling the rate of hydrolysis. Magnetic colloidal crystals (a diameter of
10.2 MUm) were formed by the aggregation of Fe3O4 and MTNs caused by the
interface phenomena during solvent evaporation in emulsion. Even the anatase
octahedrite produced from the colloidal crystal after a hydrothermal reaction
retained a magnetic saturation of 2.8 emu g(-1). This study also investigates the
photodegradation activity of our synthesized material as a photocatalyst, while
utilizing its capability for magnetic separation to prove its usefulness in
catalyst recycling.
PMID- 26428278
TI - Impact of palm date consumption on microbiota growth and large intestinal health:
a randomised, controlled, cross-over, human intervention study.
AB - The reported inverse association between the intake of plant-based foods and a
reduction in the prevalence of colorectal cancer may be partly mediated by
interactions between insoluble fibre and (poly)phenols and the intestinal
microbiota. In the present study, we assessed the impact of palm date
consumption, rich in both polyphenols and fibre, on the growth of colonic
microbiota and markers of colon cancer risk in a randomised, controlled, cross
over human intervention study. A total of twenty-two healthy human volunteers
were randomly assigned to either a control group (maltodextrin-dextrose, 37.1 g)
or an intervention group (seven dates, approximately 50 g). Each arm was of 21 d
duration and was separated by a 14-d washout period in a cross-over manner.
Changes in the growth of microbiota were assessed by fluorescence in situ
hybridisation analysis, whereas SCFA levels were assessed using HPLC. Further,
ammonia concentrations, faecal water genotoxicity and anti-proliferation ability
were also assessed using different assays, which included cell work and the Comet
assay. Accordingly, dietary intakes, anthropometric measurements and bowel
movement assessment were also carried out. Although the consumption of dates did
not induce significant changes in the growth of select bacterial groups or SCFA,
there were significant increases in bowel movements and stool frequency (P<0.01;
n 21) and significant reductions in stool ammonia concentration (P<0.05; n 21)
after consumption of dates, relative to baseline. Furthermore, date fruit intake
significantly reduced genotoxicity in human faecal water relative to control
(P<0.01; n 21). Our data indicate that consumption of date fruit may reduce colon
cancer risk without inducing changes in the microbiota.
PMID- 26428277
TI - Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an
iron-supplemented fruit drink: a double-isotope cross-over single-blind study in
women of reproductive age.
AB - Iron deficiency is common, especially among young women. Adding probiotics to
foods could be one way to increase iron absorption. The aim of this study was to
test the hypothesis that non-haem iron absorption from a fruit drink is improved
by adding Lactobacillus plantarum 299v (Lp299v). Iron absorption was studied in
healthy women of reproductive age using a single-blind cross-over design in two
trials applying the double-isotope (55Fe and 59Fe) technique. In Trial 1, iron
absorption from a fruit drink containing 109 colony-forming units (CFU) Lp299v
was compared with that from a control drink without Lp299v. Trial 2 had the same
design but 1010 CFU were used. The test and control drinks contained
approximately 5 mg of iron as ferrous lactate and were labelled with 59Fe (B) and
55Fe (A), respectively, and consumed on 4 consecutive days in the order AABB.
Retention of the isotopes was measured with whole-body counting and in blood.
Mean iron absorption from the drink containing 109 CFU Lp299v (28.6(sd 12.5) %)
was significantly higher than from the control drink (18.5(sd 5.8) %), n 10,
P<0.028). The fruit drink with 1010 CFU Lp299v gave a mean iron absorption of
29.1(sd 17.0) %, whereas the control drink gave an absorption of (20.1(sd 6.4) %)
(n 11, P<0.080). The difference in iron absorption between the 109 CFU Lp299v and
the 1010 CFU Lp299v drinks was not significant (P=0.941). In conclusion, intake
of probiotics can increase iron absorption by approximately 50 % from a fruit
drink having an already relatively high iron bioavailability.
PMID- 26428280
TI - Significantly increased PELP1 protein expression in primary and metastatic triple
negative breast carcinoma: comparison with GATA3 expression and PELP1's potential
role in triple-negative breast carcinoma.
AB - PELP1 is a novel coregulator of nuclear hormone receptors and is implicated in
playing a role in driving breast cancer and enhancing metastatic potential. The
PELP1 protein expression and potential role of PELP1 in triple-negative breast
carcinoma (TNBC) have not been well characterized. We investigated PELP1
expression by immunohistochemistry in primary and metastatic triple-negative
tumors in human tissues and compared its expression with GATA-binding protein 3
(GATA3), a novel diagnostic marker for TNBC. We examined the expression of PELP1
and GATA3 in 70 primary TNBC cases and found that PELP1 had a significantly
higher frequency of expression compared to GATA3 (96% versus 46%; P < .0001). The
mean extent score of expression of PELP1 was also significantly higher than
GATA3's expression (3.87 +/- 0.07 versus 0.91 +/- 0.15; P < .0001). PELP1 had
stronger staining intensity than GATA3. Furthermore, PELP1 immunoreactivity was
consistently maintained in paired primary and metastatic TNBC cases (100%). The
frequency of PELP1 expression (100%) in metastatic triple-negative tumors was
higher than that of GATA3 (40%) in the same tumors (P < .0001). These findings
indicate that PELP1 is a much more sensitive marker than GATA3 for TNBCs. PELP1
may have diagnostic utility for metastatic TNBC in appropriate settings, such as
history of primary TNBC in cases where the primary is negative for GATA3,
mammaglobin, and GCDFP-15. The diffuse and strong nuclear immunoreactivity of
PELP1 in most cases suggests that PELP1 may be a molecular target for the
treatment of TNBC. We hope that this study will provide insights into the role of
PELP1 in TNBC.
PMID- 26428281
TI - The effects of prophylactic bolus phenylephrine on hypotension during low-dose
spinal anesthesia for cesarean section.
AB - BACKGROUND: Continuously infused phenylephrine is frequently used to reduce the
incidence of hypotension in women undergoing cesarean section under spinal
anesthesia, but less is known about the prophylactic bolus method. We evaluated
three prophylactic bolus doses of phenylephrine during low-dose spinal anesthesia
for cesarean section. METHODS: One-hundred-and-eighty-four patients were
randomized to receive 0.9% saline 2mL (Control Group) or phenylephrine 1.0MUg/kg
(PHE1 Group), 1.5MUg/kg (PHE1.5 Group), or 2.0MUg/kg (PHE2 Group) immediately
after induction of combined spinal-epidural anesthesia. Maternal blood pressure
and heart rate were recorded at 1-min intervals until delivery. Hypotension,
defined as systolic blood pressure <80% of baseline, was treated with rescue
doses of phenylephrine 100MUg at 1-min intervals until hypotension resolved. The
incidence of nausea, vomiting, bradycardia, and hypertension, as well as Apgar
scores and umbilical blood gases, were recorded. RESULTS: The incidence of
hypotension was 71.7% (33/46) in the Control Group, 68.9% (31/45) in the PHE1
Group, 37.0% (17/46) in the PHE1.5 Group and 45.7% (21/46) in the PHE2 Group
(P=0.001). The total rescue dose of phenylephrine was greater in the Control
Group than those in the PHE1.5 Group (P<0.05) and PHE2 Group (P<0.05). The
incidence of hypertension increased as the dose of prophylactic phenylephrine
increased (P<0.001) and was highest in the PHE2 group (37%). Other variables did
not differ among the four groups. CONCLUSIONS: Under the conditions of this
study, prophylactic bolus injection of phenylephrine 1.5MUg/kg was a suitable
alternative method for reducing the incidence of hypotension during low-dose
spinal anesthesia for cesarean section.
PMID- 26428282
TI - On the Way to Speciation: Shedding Light on the Karstic Phylogeography of the
Microendemic Cave Beetle Aphaenops cerberus in the Pyrenees.
AB - The highly modified morphology and ecological features of cave-dwelling organisms
are a strong obstacle to dispersion. Hence, they represent ideal models for the
study of historical biogeography at both large and fine timescales. Here, we
study the phylogeography of Aphaenops cerberus, an endemic hypogean ground beetle
with a fragmented distribution in the French Northern Pyrenees. We extracted 75
exemplars of 17 populations of A. cerberus and sequenced one mitochondrial and
one nuclear marker to assess the geographic structuration as well as the recent
biogeographic history of this species. We used Bayesian Inference and Maximum
Likelihood to reconstruct the relationships among most of the extant populations
of this species across its distributional range. We inferred divergence time
estimates using carabid substitution rates and reconstructed haplotype networks
to investigate the recent biogeographic history of this lineage. We recover a
strong geographic structuration of the populations across the mountain range. The
strong impact of geology on the structure of the populations is evidenced
although geological continuity does not systematically lead to continual gene
flow. The origin of the species is dated from the Early Pleistocene and the
dispersal predates the main Last Glacial Maximum. Our results indicate broad
similitudes between islands and karsts, which make cave organisms an excellent
model for the study of evolution mechanisms.
PMID- 26428283
TI - Retrospective analysis of pharmacist interventions in an ambulatory palliative
care practice.
AB - BACKGROUND: We have previously reported the development of an outpatient
palliative care practice under pharmacist-physician collaboration. The Doris A.
Howell Service at the University of California, San Diego Moores Cancer Center
includes two pharmacists who participate in a transdisciplinary clinic and
provide follow-up care to patients. OBJECTIVE: This study evaluated pharmacist
interventions and patient outcomes of a pharmacist-led outpatient palliative care
practice. METHODS: This was a retrospective data analysis conducted at a single,
academic, comprehensive cancer center. New (first visit) patient consultations
were referred by an oncologist or hematologist to an outpatient palliative care
practice. A pharmacist evaluated the patient at the first visit and at follow-up
(second, third, and fourth visits). Medication problems identified, medication
changes made, and changes in pain scores were assessed. RESULTS: Eighty-four new
and 135 follow-up patient visits with the pharmacist occurred from March 2011 to
March 2012. All new patients (n = 80) were mostly women (n = 44), had localized
disease (n = 42), a gastrointestinal cancer type (n = 21), and were on a long
acting (n = 61) and short-acting (n = 70) opioid. A lack of medication efficacy
was the most common problem for symptoms of pain, constipation, and
nausea/vomiting that was identified by the pharmacist at all visits. A change in
pain medication dose and initiation of a new medication for constipation and
nausea/vomiting were the most common interventions by the pharmacist. A
statistically significant change in pain score was observed for the third visit,
but not for the second and fourth visits. CONCLUSIONS: A pharmacist-led
outpatient palliative care practice identified medication problems for management
of pain, constipation, and nausea/vomiting. Medication changes involved a change
in dose and/or initiating a new medication. Trends were observed in improvement
and stabilization of pain over subsequent clinic visits.
PMID- 26428284
TI - Compatibility of epirubicin-loaded DC beadTM with different non-ionic contrast
media.
AB - PURPOSE: The aim of this study was to determine the compatibility of epirubicin
loaded DC beadTM with different non-ionic contrast media over a period of seven
days when stored light protected under refrigerated conditions. METHODS: DC
beadTM (2 ml) (Biocompatibles UK Ltd) of the bead size 70-150 um ( = DC bead M1)
or bead size 100-300 um were loaded with 75 mg epirubicin powder formulation
(Farmorubicin(r) dissolved in 3 ml water for injection to a concentration of 25
mg/ml) or 76 mg epirubicin injection solution (Epimedac(r) 2 mg/ml) within 2 h or
6 h, respectively. After removal of the excess solution, the epirubicin-loaded
beads were mixed in polypropylene syringes with an equal volume (~1.5 ml) of
contrast media, i.e. AccupaqueTM 300 (Nycomed Inc.), Imeron(r) 300 (Bracco
S.p.A), Ultravist(r) 300 (Bayer Pharma AG), VisipaqueTM 320 (GE Healthcare) and
agitated in a controlled manner to get a homogenous suspension. Syringes with
loaded beads in contrast media were stored protected from light under
refrigeration (2-8C). Compatibility was determined by measuring epirubicin
concentrations in the suspensions in triplicate on day 0, 1, and 7. A reversed
phase high-performance liquid chromatography assay with ultraviolet detection was
utilized to analyze the concentration and purity of epirubicin. RESULTS: Mixing
of epirubicin-loaded beads with different non-ionic contrast media released 0.1
0.5% of epirubicin over a period of 24 h, irrespectively, of the DC beadTM size
or type of contrast media. No further elution or degradation was observed after
seven days when the admixtures were stored protected from light under
refrigeration. CONCLUSION: Compatibility of epirubicin-loaded DC beadTM with an
equal volume of different contrast media in polypropylene syringes is given over
a period of seven days. Due to a maximum elution of 0.1-0.5% of epirubicin from
loaded DC beadTM, admixtures with contrast media can be prepared in advance in
centralized cytotoxic preparation units. Microbiological aspects have to be
considered when determining the expiration date of the product.
PMID- 26428286
TI - Increased appropriateness of customized alert acknowledgement reasons for
overridden medication alerts in a computerized provider order entry system.
AB - OBJECTIVE: Computerized provider order entry systems commonly contain alerting
mechanisms for patient allergies, incorrect doses, or drug-drug interactions when
ordering medications. Providers have the option to override (bypass) these alerts
and continue with the order unchanged. This study examines the effect of
customizing medication alert override options on the appropriateness of override
selection related to patient allergies, drug dosing, and drug-drug interactions
when ordering medications in an electronic medical record. MATERIALS AND METHODS:
In this prospective, randomized crossover study, providers were randomized into
cohorts that required a reason for overriding a medication alert from a
customized or non-customized list of override reasons and/or by free-text entry.
The primary outcome was to compare override responses that appropriately
correlate with the alert type between the customized and non-customized
configurations. The appropriateness of a subset of free-text responses that
represented an affirmative and active acknowledgement of the alert without
further explanation was classified as "indeterminate." Results were analyzed in
three different ways by classifying indeterminate answers as either appropriate,
inappropriate, or excluded entirely. Secondary outcomes included the
appropriateness of override reasons when comparing cohorts and individual
providers, reason selection based on order within the override list, and the
determination of the frequency of free-text use, nonsensical responses, and
multiple selection responses. RESULTS: Twenty-two clinicians were randomized into
2 cohorts and a total of 1829 alerts with a required response were generated
during the study period. The customized configuration had a higher rate of
appropriateness when compared to the non-customized configuration regardless of
how indeterminate responses were classified (p<0.001). When comparing cohorts,
appropriateness was significantly higher in the customized configuration
regardless of the classification of indeterminate responses (p<0.001) with one
exception: when indeterminate responses were considered inappropriate for the
cohort of providers that were first exposed to the non-customized list (p=0.103).
Free-text use was higher in the customized configuration overall (p<0.001), and
there was no difference in nonsensical response between configurations (p=0.39).
CONCLUSION: There is a benefit realized by using a customized list for medication
override reasons. Poor application design or configuration can negatively affect
provider behavior when responding to important medication alerts.
PMID- 26428285
TI - Italian guidelines for the management and treatment of neonatal cholestasis.
AB - Hyperbilirubinemia is a frequent condition affecting newborns during the first
two weeks of life and when it lasts more than 14 days it is defined as prolonged
jaundice. This condition requires differential diagnosis between the usually
benign unconjugated hyperbilirubinemia and the pathological conjugated
hyperbilirubinemia, that is mainly due to neonatal cholestasis. It is important
that the diagnosis of neonatal cholestasis be well-timed to optimize its
management, prevent worsening of the patient's outcome, and to avoid premature,
painful, expensive, and useless tests. Unfortunately, this does not always occur
and, therefore, the Task Force on Hyperbilirubinemia of the Italian Society of
Neonatology presents these shared Italian guidelines for the management and
treatment of neonatal cholestasis whose overall aim is to provide a useful tool
for its assessment for neonatologists and family pediatricians.
PMID- 26428287
TI - Combination of gaps in noise detection and visual analog scale for measuring
tinnitus components in patients treated with repetitive transcranial magnetic
stimulation.
AB - OBJECTIVES: We aimed to evaluate gaps in noise (GIN) detection and visual analog
scale (VAS) for measuring perceived tinnitus loudness and annoyance caused
thereby. We quantified the outcomes and effectiveness of repetitive transcranial
magnetic stimulation (rTMS) on chronic tinnitus. METHODS: Fourteen tinnitus
patients with normal hearing underwent a 10 day course of active 1-Hz rTMS to the
left region of the temporoparietal cortex. GIN (in which the matched pitch and
loudness of tinnitus was used to determine the frequency and intensity of
background noise) and VAS was used to assess tinnitus loudness and the extent of
annoyance caused thereby. Both ten patients with tinnitus who underwent left
temporoparietal sham stimulation and fifteen volunteers with normal hearing
without tinnitus participated with GIN detection as a control. Correlations
between VAS scores and GIN detection were determined via Spearman's correlation
analysis. RESULTS: The mean GIN thresholds of tinnitus-affected (5.87 ms) ears
and the ears of control subjects (4.85 ms) differed significantly. In the
tinnitus group, 42.8% (6/14) patients experienced significant reductions in
tinnitus annoyance, as assessed by VAS. 71.4% (10/14) patients experienced
significant reductions in tinnitus loudness, as evidenced by GIN evaluation.
Three tinnitus subjects (21.4%) achieved 30% decrease of the threshold of GIN
detection. There was no significant change in GIN detection and VAS scores after
sham stimulation. A significant positive correlation was evident between GIN data
and VAS scores (r=0.84, p<0.001). CONCLUSIONS: Gaps in noise detection, combined
with VAS scores, affords a promising sensitive method by which to evaluate
tinnitus loudness and annoyance. Low frequency rTMS significantly decreased
tinnitus after the active, but not the sham, treatment.
PMID- 26428288
TI - Pseudoknots in RNA folding landscapes.
AB - MOTIVATION: The function of an RNA molecule is not only linked to its native
structure, which is usually taken to be the ground state of its folding
landscape, but also in many cases crucially depends on the details of the folding
pathways such as stable folding intermediates or the timing of the folding
process itself. To model and understand these processes, it is necessary to go
beyond ground state structures. The study of rugged RNA folding landscapes holds
the key to answer these questions. Efficient coarse-graining methods are required
to reduce the intractably vast energy landscapes into condensed representations
such as barrier trees or basin hopping graphs : BHG) that convey an approximate
but comprehensive picture of the folding kinetics. So far, exact and heuristic
coarse-graining methods have been mostly restricted to the pseudoknot-free
secondary structures. Pseudoknots, which are common motifs and have been
repeatedly hypothesized to play an important role in guiding folding
trajectories, were usually excluded. RESULTS: We generalize the BHG framework to
include pseudoknotted RNA structures and systematically study the differences in
predicted folding behavior depending on whether pseudoknotted structures are
allowed to occur as folding intermediates or not. We observe that RNAs with
pseudoknotted ground state structures tend to have more pseudoknotted folding
intermediates than RNAs with pseudoknot-free ground state structures. The
occurrence and influence of pseudoknotted intermediates on the folding pathway,
however, appear to depend very strongly on the individual RNAs so that no general
rule can be inferred. AVAILABILITY AND IMPLEMENTATION: The algorithms described
here are implemented in C++ as standalone programs. Its source code and
Supplemental material can be freely downloaded from
http://www.tbi.univie.ac.at/bhg.html. CONTACT: qin@bioinf.uni-leipzig.de
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
online.
PMID- 26428289
TI - Generalized empirical Bayesian methods for discovery of differential data in high
throughput biology.
AB - MOTIVATION: High-throughput data are now commonplace in biological research.
Rapidly changing technologies and application mean that novel methods for
detecting differential behaviour that account for a 'large P, small n' setting
are required at an increasing rate. The development of such methods is, in
general, being done on an ad hoc basis, requiring further development cycles and
a lack of standardization between analyses. RESULTS: We present here a
generalized method for identifying differential behaviour within high-throughput
biological data through empirical Bayesian methods. This approach is based on our
baySeq algorithm for identification of differential expression in RNA-seq data
based on a negative binomial distribution, and in paired data based on a beta
binomial distribution. Here we show how the same empirical Bayesian approach can
be applied to any parametric distribution, removing the need for lengthy
development of novel methods for differently distributed data. Comparisons with
existing methods developed to address specific problems in high-throughput
biological data show that these generic methods can achieve equivalent or better
performance. A number of enhancements to the basic algorithm are also presented
to increase flexibility and reduce computational costs. AVAILABILITY AND
IMPLEMENTATION: The methods are implemented in the R baySeq (v2) package,
available on Bioconductor
http://www.bioconductor.org/packages/release/bioc/html/baySeq.html. CONTACT:
tjh48@cam.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at
Bioinformatics online.
PMID- 26428290
TI - cl-dash: rapid configuration and deployment of Hadoop clusters for bioinformatics
research in the cloud.
AB - : One of the solutions proposed for addressing the challenge of the overwhelming
abundance of genomic sequence and other biological data is the use of the Hadoop
computing framework. Appropriate tools are needed to set up computational
environments that facilitate research of novel bioinformatics methodology using
Hadoop. Here, we present cl-dash, a complete starter kit for setting up such an
environment. Configuring and deploying new Hadoop clusters can be done in
minutes. Use of Amazon Web Services ensures no initial investment and minimal
operation costs. Two sample bioinformatics applications help the researcher
understand and learn the principles of implementing an algorithm using the
MapReduce programming pattern. AVAILABILITY AND IMPLEMENTATION: Source code is
available at https://bitbucket.org/booz-allen-sci-comp-team/cl-dash.git. CONTACT:
hodor_paul@bah.com.
PMID- 26428291
TI - ALP & FALP: C++ libraries for pairwise local alignment E-values.
AB - MOTIVATION: Pairwise local alignment is an indispensable tool for molecular
biologists. In real time (i.e. in about 1 s), ALP (Ascending Ladder Program)
calculates the E-values for protein-protein or DNA-DNA local alignments of random
sequences, for arbitrary substitution score matrix, gap costs and letter
abundances; and FALP (Frameshift Ascending Ladder Program) performs a similar
task, although more slowly, for frameshifting DNA-protein alignments.
AVAILABILITY AND IMPLEMENTATION: To permit other C++ programmers to implement the
computational efficiencies in ALP and FALP directly within their own programs,
C++ source codes are available in the public domain at http://go.usa.gov/3GTSW
under 'ALP' and 'FALP', along with the standalone programs ALP and FALP. CONTACT:
spouge@nih.gov SUPPLEMENTARY INFORMATION: Supplementary data are available at
Bioinformatics online.
PMID- 26428292
TI - Qualimap 2: advanced multi-sample quality control for high-throughput sequencing
data.
AB - MOTIVATION: Detection of random errors and systematic biases is a crucial step of
a robust pipeline for processing high-throughput sequencing (HTS) data.
Bioinformatics software tools capable of performing this task are available,
either for general analysis of HTS data or targeted to a specific sequencing
technology. However, most of the existing QC instruments only allow processing of
one sample at a time. RESULTS: Qualimap 2 represents a next step in the QC
analysis of HTS data. Along with comprehensive single-sample analysis of
alignment data, it includes new modes that allow simultaneous processing and
comparison of multiple samples. As with the first version, the new features are
available via both graphical and command line interface. Additionally, it
includes a large number of improvements proposed by the user community.
AVAILABILITY AND IMPLEMENTATION: The implementation of the software along with
documentation is freely available at http://www.qualimap.org. CONTACT:
meyer@mpiib-berlin.mpg.de SUPPLEMENTARY INFORMATION: Supplementary data are
available at Bioinformatics online.
PMID- 26428293
TI - JEPEGMIX: gene-level joint analysis of functional SNPs in cosmopolitan cohorts.
AB - MOTIVATION: To increase detection power, gene level analysis methods are used to
aggregate weak signals. To greatly increase computational efficiency, most
methods use as input summary statistics from genome-wide association studies
(GWAS). Subsequently, gene statistics are constructed using linkage
disequilibrium (LD) patterns from a relevant reference panel. However, all
methods, including our own Joint Effect on Phenotype of eQTL/functional single
nucleotide polymorphisms (SNPs) associated with a Gene (JEPEG), assume
homogeneous panels, e.g. European. However, this renders these tools unsuitable
for the analysis of large cosmopolitan cohorts. RESULTS: We propose a JEPEG
extension, JEPEGMIX, which similar to one of our software tools, Direct
Imputation of summary STatistics of unmeasured SNPs from MIXed ethnicity cohorts,
is capable of estimating accurate LD patterns for cosmopolitan cohorts. JEPEGMIX
uses this accurate LD estimates to (i) impute the summary statistics at
unmeasured functional variants and (ii) test for the joint effect of all measured
and imputed functional variants which are associated with a gene. We illustrate
the performance of our tool by analyzing the GWAS meta-analysis summary
statistics from the multi-ethnic Psychiatric Genomics Consortium Schizophrenia
stage 2 cohort. This practical application supports the immune system being one
of the main drivers of the process leading to schizophrenia. AVAILABILITY AND
IMPLEMENTATION: Software, annotation database and examples are available at
http://dleelab.github.io/jepegmix/. CONTACT: donghyung.lee@vcuhealth.org
SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics
online.
PMID- 26428294
TI - Cell line name recognition in support of the identification of synthetic
lethality in cancer from text.
AB - MOTIVATION: The recognition and normalization of cell line names in text is an
important task in biomedical text mining research, facilitating for instance the
identification of synthetically lethal genes from the literature. While several
tools have previously been developed to address cell line recognition, it is
unclear whether available systems can perform sufficiently well in realistic and
broad-coverage applications such as extracting synthetically lethal genes from
the cancer literature. In this study, we revisit the cell line name recognition
task, evaluating both available systems and newly introduced methods on various
resources to obtain a reliable tagger not tied to any specific subdomain. In
support of this task, we introduce two text collections manually annotated for
cell line names: the broad-coverage corpus Gellus and CLL, a focused target
domain corpus. RESULTS: We find that the best performance is achieved using
NERsuite, a machine learning system based on Conditional Random Fields, trained
on the Gellus corpus and supported with a dictionary of cell line names. The
system achieves an F-score of 88.46% on the test set of Gellus and 85.98% on the
independently annotated CLL corpus. It was further applied at large scale to 24
302 102 unannotated articles, resulting in the identification of 5 181 342 cell
line mentions, normalized to 11 755 unique cell line database identifiers.
AVAILABILITY AND IMPLEMENTATION: The manually annotated datasets, the cell line
dictionary, derived corpora, NERsuite models and the results of the large-scale
run on unannotated texts are available under open licenses at
http://turkunlp.github.io/Cell-line-recognition/. CONTACT: sukaew@utu.fi.
PMID- 26428295
TI - Mutational and network level mechanisms underlying resistance to anti-cancer
kinase inhibitors.
AB - Tyrosine-specific and other protein kinases are embedded in signaling networks
critical for progression of tumors of all types. Hence, kinase inhibitors have
nucleated a major arm of personalized cancer therapy. Unfortunately, almost all
kinase inhibitors evoke resistance within a year or two, due to secondary
mutations, and other alterations within the targeted kinase, or due to emergence
of feedback regulatory loops that compensate for extinguished kinases. We review
clinically approved kinase inhibitors and the emergence of resistance in
leukemia, melanoma, lung and breast tumors, and draw parallel lines in terms of
secondary mutations and compensatory mechanisms. Currently emerging are
pharmacological strategies able to circumvent resistance and re-sensitize
patients to therapeutic treatments. They include second and third generation
inhibitors that overcome new mutations, novel drug combinations that
simultaneously block the primary oncogenic pathway and compensatory routes, as
well as monoclonal antibodies. Deeper understanding of biological signaling
networks and their responses to perturbations will aid in the development of
effective therapies for patients with cancer.
PMID- 26428297
TI - Gliding motility in apicomplexan parasites.
AB - Apicomplexan parasites, including Plasmodium and Toxoplasma, employ a unique form
of substrate-dependent locomotion known as gliding motility. In these obligate,
intracellular parasites, gliding motility is used for migration through the
tissues and cells of the host, for active penetration of the host cell, and, at
times, for proactive egress from the host. Gliding motility is powered by an
actin-myosin based motor apparatus, known as the glideosome, which is situated
within the elaborate cortical domain of the parasite. In this system, myosin is
anchored to an internal membrane complex and drives the rearward translocation of
actin-associated cell surface adhesins, thus leading to forward movement of the
parasite. This review outlines our current understanding of glideosome
architecture and the molecular basis of parasite motility.
PMID- 26428296
TI - Metabolic fibroblast growth factors (FGFs): Mediators of energy homeostasis.
AB - The metabolic fibroblast growth factors (FGFs), FGF1, FGF15/19, and FGF21 differ
from classic FGFs in that they modulate energy homeostasis in response to
fluctuating nutrient availability. These unique mediators of metabolism regulate
a number of physiological processes which contribute to their potent
pharmacological properties. Administration of pharmacological doses of these FGFs
causes weight loss, increases energy expenditure, and improves carbohydrate and
lipid metabolism in obese animal models. However, many questions remain regarding
the precise molecular and physiological mechanisms governing the effects of
individual metabolic FGFs. Here we review the metabolic actions of FGF1,
FGF15/19, and FGF21 while providing insights into their pharmacological effects
by examining known biological functions.
PMID- 26428298
TI - Maternal and reproductive health financing in Burundi: public-sector contribution
levels and trends from 2010 to 2012.
AB - BACKGROUND: An understanding of public financial flows to reproductive health
(RH) at the country level is key to assessing the extent to which they correspond
to political commitments. This is especially relevant for low-income countries
facing important challenges in the area of RH. To this end, the present study
analyzes public expenditure levels and trends with regards to RH in Burundi
between the years 2010 to 2012, looking specifically at financing agents, health
providers, and health functions. METHODS: The analysis was performed using
standard RH sub-account methodology. Information regarding public expenditures
was gathered from national budgets, the Burundi Ministry of Public Health
information system, and from other relevant public institutions. RESULTS: Public
RH expenditures in Burundi accounted for $41.163 million international dollars in
2012, which represents an increase of 16 % from 2010. In 2012, this sum
represented 0.57 % of the national GDP. The share of total public health spending
allocated to RH increased from 15 % in 2010 to 19 % in 2012. In terms of public
agents involved in RH financing, the Ministry of Public Health proved to play the
most important role. Half of all public RH spending went to primary health care
clinics, while more than 70 % of this money was used for maternal health; average
public RH spending per woman of childbearing age stagnated during the study
period. CONCLUSIONS: The flow patterns and levels of public funds to RH in
Burundi suggest that RH funding correctly reflects governmental priorities for
the period between 2010 and 2012. In a context of general shrinking donor
commitment, local governments have come to play a key role in ensuring the
efficient use of available resources and the mobilizing of additional domestic
funding. A strong and transparent financial tracking system is key to carrying
out this role and making progress towards the MDG Goals and development beyond
2015.
PMID- 26428299
TI - Improving Properties of Recombinant SsoPox by Site-Specific Pegylation.
AB - SsoPox, a ~35 kDa enzyme from Sulfolobus solfataricus, can hydrolyze and
inactivate a variety of organophosphate (OP)-compounds. The enzyme is a potential
candidate for the development of prophylactic and therapeutic agent against OP
poisoning in humans. However, the therapeutic use of recombinant SsoPox suffers
from certain limitations associated with the use of recombinant protein
pharmaceuticals. Some of these limitations could be overcome by conjugating
SsoPox enzyme with polyethylene glycol (PEG). In this study, we report generation
and in vitro characterization of N-terminal mono-PEGylated rSsoPox(2p) (a variant
of rSsoPox(wt) having enhanced OP-hydrolyzing activity). The enzyme was PEGylated
with mPEG-propionaldehyde and the PEGylated protein was isolated using ion
exchange chromatography. Compared with the unmodified enzyme, mono-PEGylation of
rSsoPox results in improvement in the thermostability and protease resistance of
the enzyme. PEGylated rSsoPox(2p) can be developed as a candidate for the
prevention / treatment of OP-poisoning.
PMID- 26428300
TI - Amyloid-like Fibril Formation by Trypsin in Aqueous Ethanol. Inhibition of
Fibrillation by PEG.
AB - The formation of amyloid-like fibrils was studied by using the well-known serine
protease trypsin as a model protein in the presence of ethanol as organic
solvent. Trypsin forms amyloid-like fibrils in aqueous ethanol at pH = 7.0. The
dye Congo red (CR) was used to detect the presence of amyloid-like fibrils in the
samples. The binding of CR to fibrils led to an increase in absorption intensity
and a red shift in the absorption band of CR. Thioflavin T (ThT) and 8-anilino-1-
naphthalenesulfonic acid (ANS) binding assays were employed to characterize
amyloid-like fibril formation. The ThT binding assay revealed that the protein
exhibited maximum aggregation in 60% (v/v) ethanol after incubation for 24 h at
24 (o)C. The ANS binding results indicated that the hydrophobic residues were
more exposed to the solvent in the aggregated form of the protein. The effects of
polyethylene glycol (PEG) on the formation of amyloid-like fibrils was studied in
vitro. The aggregation of trypsin was followed via the kinetics of aggregation,
the far-UV circular dichroism (CD) and transmission electron microscopy (TEM) in
the presence and absence of PEG. The CD measurements indicated that the protein
aggregates have a cross-beta structure in 60% ethanol. TEM revealed that trypsin
forms fibrils with a thread-like structure. The inhibitory effect of PEG on the
aggregation of trypsin increased with rising PEG concentration. PEG therefore
inhibits the formation of amyloid-like fibrils of trypsin in aqueous ethanol.
PMID- 26428301
TI - NatHER: protocol for systematic evaluation of trends in survival among patients
with HER2-positive advanced breast cancer.
AB - BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive metastatic
breast cancer (MBC) is an aggressive form of breast cancer and is historically
associated with poor outcomes compared with HER2-negative MBC. Since 1998, four
drugs have been globally approved for the targeted treatment of HER2-positive
MBC. Additional advances in patient care-such as improved breast cancer
screening, HER2 testing, and supportive care-have also occurred. The objective of
this systematic review and meta-analysis is to determine whether there has been a
cumulative change in survival over time in patients with HER2-positive advanced
breast cancer based on results from interventional clinical trials (ICTs) and
observational studies and to compare outcomes across these types of studies.
METHODS/DESIGN: A systematic search of Medline, EMBASE, and the Cochrane Central
Register of Controlled Trials will be performed. Two investigators will
independently assess each abstract for inclusion. English language reports of
ICTs and observational studies that include patients with HER2-positive advanced
breast cancer from 1987 onwards will be considered. The primary outcome of
interest is overall survival; secondary outcomes include progression-free
survival and safety. Data on clinical outcomes, as well as on study design, study
population, treatment/intervention, methodological quality, and outcomes, will be
extracted using a structured codebook developed by the authors for this study.
Standard and cumulative random effects meta-analysis will be performed to derive
pooled risk estimates, both overall and by study design, controlling for
covariates such as aggregate demographic and clinical characteristics of
patients, treatment/intervention, and study characteristics. Heterogeneity of
studies will be evaluated using the I(2) statistic. Differences in risk estimates
by quality characteristics will be performed using meta-regression. DISCUSSION:
This study will evaluate current and evolving trends in survival associated with
HER2-positive advanced breast cancer over nearly 30 years and will build upon
prior, less comprehensive, systematic analyses. This information is important to
patients, healthcare providers, and researchers, particularly in the advanced
disease setting, in which new therapies have been recently approved. Including
observational studies allows us to evaluate real-world effectiveness; useful
information will be gained by comparing findings from observational studies with
those from ICTs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014014345.
PMID- 26428303
TI - A determinant of disease symptom severity is located in RNA2 of broad bean wilt
virus 2.
AB - Broad bean wilt virus 2 (BBWV2), which belongs to the genus Fabavirus, is a
destructive pathogen of many economically important horticultural and ornamental
crops. In this study, we constructed infectious full-length cDNA clones of two
distinct isolates of BBWV2 under control of the cauliflower mosaic virus 35S
promoter. BBWV2-PAP1 isolated from paprika (Capsicum annuum var. gulosum) induces
severe disease symptoms in various pepper varieties, whereas BBWV2-RP1 isolated
from red pepper (Capsicum annuum L.) causes mild symptoms. Agrobacterium-mediated
inoculation of the infectious cDNA clones of BBWV2-PAP1 and RP1 resulted in the
same symptoms as the original virus isolates. The infectious cDNA clones of BBWV2
PAP1 and RP1 were used to examine the symptoms induced by pseudorecombinants
between the two isolates to localize in which of the two genomic RNAs are the
symptom severity determinants in BBWV2. The pseudorecombinant of RP1-RNA1 and
PAP1-RNA2 induced severe symptoms, similar to those caused by the parental
isolate PAP1, whereas the pseudorecombinant of PAP1-RNA1 and RP1-RNA2 induced
mild symptoms, similar to those caused by the parental isolate RP1. Our results
suggest that BBWV2 RNA2 contains a symptom determinant(s) capable of enhancing
symptom severity.
PMID- 26428302
TI - The NESH/Abi-3-based WAVE2 complex is functionally distinct from the Abi-1-based
WAVE2 complex.
AB - BACKGROUND: Abl interactor (Abi) family proteins play significant roles in actin
cytoskeleton organization through participation in the WAVE complex. Mammals
possess three Abi proteins: Abi-1, Abi-2, and NESH/Abi-3. Abi-1 and Abi-2 were
originally identified as Abl tyrosine kinase-binding proteins. It has been
disclosed that Abi-1 acts as a bridge between c-Abl and WAVE2, and c-Abl-mediated
WAVE2 phosphorylation promotes actin remodeling. We showed previously that
NESH/Abi-3 is present in the WAVE2 complex, but neither binds to c-Abl nor
promotes c-Abl-mediated phosphorylation of WAVE2. RESULTS: In this study, we
characterized NESH/Abi-3 in more detail, and compared its properties with those
of Abi-1 and Abi-2. NESH/Abi-3 was ectopically expressed in NIH3T3 cells, in
which Abi-1, but not NESH/Abi-3, is expressed. The expression of NESH/Abi-3
caused degradation of endogenous Abi-1, which led to the formation of a NESH/Abi
3-based WAVE2 complex. When these cells were plated on fibronectin-coated dishes,
the translocation of WAVE2 to the plasma membrane was significantly reduced and
the formation of peripheral lamellipodial structures was disturbed, suggesting
that the NESH/Abi-3-based WAVE2 complex was unable to help produce lamellipodial
protrusions. Next, Abi-1, Abi-2, or NESH/Abi-3 was expressed in v-src-transformed
NIH3T3 cells. Only in NESH/Abi-3-expressed cells did treatment with an Abl kinase
inhibitor, imatinib mesylate, or siRNA-mediated knockdown of c-Abl promote the
formation of invadopodia, which are ventral membrane protrusions with
extracellular matrix degradation activity. Structural studies showed that a
linker region between the proline-rich regions and the Src homology 3 (SH3)
domain of Abi-1 is crucial for its interaction with c-Abl and c-Abl-mediated
phosphorylation of WAVE2. CONCLUSIONS: The NESH/Abi-3-based WAVE2 complex is
functionally distinct from the Abi-1-based one, and NESH/Abi-3 may be involved in
the formation of ventral protrusions under certain conditions.
PMID- 26428304
TI - The phosphoprotein genes of measles viruses from subacute sclerosing
panencephalitis cases encode functional as well as non-functional proteins and
display reduced editing.
AB - Products expressed from the second (P/V/C) gene are important in replication and
abrogating innate immune responses during acute measles virus (MV) infection.
Thirteen clone sets were derived from the P/V/C genes of measles virus (MV) RNA
extracted from brains of a unique collection of seven cases of subacute
sclerosing panencephalitis (SSPE) caused by persistent MV in the central nervous
system (CNS). Whether these functions are fully maintained when MV replicates in
the CNS has not been previously determined. Co-transcriptional editing of the P
mRNAs by non-template insertion of guanine (G) nucleotides, which generates mRNAs
encoding the viral V protein, occurs much less frequently (9%) in the SSPE
derived samples than during the acute infection (30-50%). Thus it is likely that
less V protein, which is involved in combatting the innate immune response, is
produced. The P genes in MV from SSPE cases were not altered by biased
hypermutation but exhibited a high degree of variation within each case. Most but
not all SSPE derived phospho-(P) proteins were functional in mini genome
replication/transcription assays. An eight amino acid truncation of the carboxyl
terminus made the P protein non-functional while the insertion of an additional
glycine residue by insertion of G nucleotides at the editing site had no effect
on protein function.
PMID- 26428305
TI - Comparison of reproductive outcome in oligozoospermic men with high sperm DNA
fragmentation undergoing intracytoplasmic sperm injection with ejaculated and
testicular sperm.
AB - OBJECTIVE: To investigate the effectiveness of intracytoplasmic sperm injection
(ICSI) using testicular sperm as a strategy to overcome infertility in men with
high sperm DNA fragmentation (SDF). DESIGN: Prospective, observational, cohort
study. SETTING: Private IVF centers. PATIENT(S): A total of 147 couples
undergoing IVF-ICSI and day 3 fresh ETs whose male partner has oligozoospermia
and high SDF. INTERVENTION(S): Sperm injections were carried out with ejaculated
sperm (EJA-ICSI) or testicular sperm (TESTI-ICSI) retrieved by either testicular
sperm extraction (TESE) or testicular sperm aspiration (TESA). SDF levels were
reassessed on the day of oocyte retrieval in both ejaculated and testicular
specimens. MAIN OUTCOME MEASURE(S): Percentage of testicular and ejaculated
spermatozoa containing fragmented DNA (%DFI) and clinical pregnancy, miscarriage,
and live-birth rates. RESULT(S): The %DFI in testicular sperm was 8.3%, compared
with 40.7% in ejaculated sperm. For the TESTI-ICSI group versus the EJA-ICSI
group, respectively, the clinical pregnancy rate was 51.9% and 40.2%, the
miscarriage rate was 10.0% and 34.3%, and the live-birth rate was 46.7% and
26.4%. CONCLUSION(S): ICSI outcomes were significantly better in the group of men
who had testicular sperm used for ICSI compared with those with ejaculated sperm.
SDF was significantly lower in testicular specimens compared with ejaculated
counterparts. Our results suggest that TESTI-ICSI is an effective option to
overcome infertility when applied to selected men with oligozoospermia and high
ejaculated SDF levels.
PMID- 26428306
TI - Results of centralized Asherman surgery, 2003-2013.
AB - OBJECTIVE: To study the success rate of hysteroscopic adhesiolysis and the
spontaneous recurrence rate of intrauterine adhesions (IUAs) in patients with
Asherman syndrome. DESIGN: Cohort study. SETTING: University-affiliated
hospitals. PATIENT(S): A total of 638 women with Asherman syndrome were included,
all diagnosed using hysteroscopy, and operated on between 2003 and 2013.
INTERVENTION(S): Hysteroscopic adhesiolysis. MAIN OUTCOME MEASURE(S):
Hysteroscopic adhesiolysis was classified as successful if a normalization of
menstrual blood flow occurred, along with a restored, healthy, cavity anatomy,
free of adhesions, with hysteroscopic visualization of >= 1 tubal ostium.
Recurrences of adhesions were diagnosed using hysteroscopy after an initial
successful procedure. RESULT(S): A first-trimester procedure preceded Asherman
syndrome in 371 women (58.2%) and caused adhesions of grades 1-2A. In 243 (38.1%)
women, a postpartum procedure caused IUAs of grades 3-5. The procedure was
successful in 606 women (95%), and restoration of menstrual blood flow occurred
in 97.8%; IUAs spontaneously recurred in 174 (27.3%) of these cases. High grades
of adhesions were predictive of a higher chance of spontaneous recurrence of
adhesions. CONCLUSION(S): In 95% of women with Asherman syndrome, a healthy
uterine cavity was restored with hysteroscopic adhesiolysis, in 1-3 attempts,
with a 28.7% recurrence rate of spontaneous IUAs.
PMID- 26428307
TI - Prostatic relapse of an undifferentiated teratoma 24 years after orchidectomy.
AB - BACKGROUND: Non-seminomatous germ cell tumours make up about 40 % of all germ
cell tumours, which in turn are the most common tumours in men aged 15-44 years.
Low risk stage I non-seminomatous germ cell tumours, which are confined to the
testes, are commonly treated by orchiectomy and surveillance. Up to 20 % of
patients with this diagnosis relapse, usually within 1-2 years of follow up, but
very rarely after more than 5 years. The most common sites of relapse are the
retroperitoneal lymph nodes, the mediastinum, and the lungs. We describe a case
of relapse in the prostate over 20 years after initial diagnosis, which has not
been described in the literature so far. CASE PRESENTATION: This report presents
a 49-year-old white British man with relapsed testicular non-seminomatous germ
cell tumour 22 years after initial treatment with orchidectomy only. He relapsed
with a prostatic mass, haematospermia and back pain. His prostate specific
antigen levels were within normal range. Alpha feto-protein and lactate
dehydrogenase levels were elevated, and his human chorionic gonadotrophin levels
were normal. A biopsy confirmed undifferentiated malignant tumour, shown
immunohistochemically to be a yolk sac tumour. The patient was initially treated
with bleomycin, etoposide and cisplatin chemotherapy, but developed bleomycin
related pulmonary side effects after two cycles. His treatment was changed and he
completed four cycles of chemotherapy by receiving two cycles of etoposide,
ifosfamide, and cisplatin. Post treatment blood tumour markers were normal, but a
follow up computed tomography showed a mass in the base of the prostate, the
trigone and the left distal ureter which was surgically resected. The histology
from the surgical resection was of necrotic tissue. The patient is now in follow
up at 3 years after treatment with no evidence of residual disease on computed
tomography. His Alpha feto-protein, beta human chorionic gonadotrophin and
lactate dehydrogenase levels are normal. CONCLUSIONS: Very late relapse in stage
I non-seminomatous germ cell tumours is extremely rare and the prostate is a
highly unusual site of relapsed disease. For diagnosis of late relapse, this case
confirms the value of serum biomarkers in germ cell tumours, in particular non
seminomatous germ cell tumours.
PMID- 26428308
TI - LRP1B deletion is associated with poor outcome for glioblastoma patients.
AB - INTRODUCTION: Deletion of the tumor suppressor gene LRP1B has been reported in
glioblastoma, the most aggressive primary brain tumor in adults. Our objective
was to analyze frequency and prognostic impact of LRP1B deletion and expression
levels. METHODS: We retrospectively included all the primary IDH1/2 wild-type GBM
patients with available clinical follow-up, DNA and RNA from our database.
Deletions were analyzed by SNP-array. LRP1B mRNA expression was analyzed by
reverse transcription quantitative polymerase chain reaction. RESULTS: 178
patients were included with a median age of 62.36 years. LRP1B deletions were
observed for 10.1% of patients (complete: 2.8%, partial: 7.3%). LRP1B deletions
were associated with poor progression-free survival (PFS) (p=0.004) and overall
survival (OS) (p=0.001). By multivariate analysis, LRP1B deletions remained
significant for both PFS (p=0.003, hazard ratio (HR): 2.261) and OS (p=0.001, HR:
2.609). LRP1B was down expressed with a mean relative expression of 46%
comparatively to normal tissue. No association between LRP1B mRNA and patient
outcome was observed. No correlation was found between the deletions and the mRNA
down-expression. These results were validated using GBM TCGA data. CONCLUSION:
LRP1B presents with frequent molecular alterations which impact patient outcome,
highlighting the potential interest of this gene for glioblastoma patients.
PMID- 26428309
TI - Scales for hyperkinetic disorders: A systematic review.
AB - Hyperkinetic movement disorders represent a heterogeneous group of disorders in
which involuntary movements are the prevalent clinical symptoms. The five main
categories of hyperkinetic disorders are tremor, dystonia, tics,myoclonus and
drug-induced dyskinesia.The severity of hyperkinetic disorders is assessed by all
clinicians when they examine a patient; quantifying the severity also provides a
means of studying the natural history of a given disorder and the possible effect
of new therapeutic interventions. This means that good rating instruments are
required in both everyday practice and experimental settings. Unfortunately, the
clinical evaluation of these disorders is complicated by the inherent nature and
variability over time of involuntary movements. A number of scales have been
proposed over the years to study the various hyperkinetic disorders. The aim of
this review is to systematically identify all the clinical scales that have been
proposed and to classify them according to the criteria developed by the Movement
Disorder Society (MDS) task force for rating scales in Parkinson's disease.On the
basis of this methodology, a scale may be defined as 'Recommended', 'Suggested'
or 'Listed' in decreasing order of value.We found that, although numerous scales
aimed at assessing hyperkinetic disorders have been published, their variability
in terms of clinimetric properties, availability and effort required to
administer them is high. In this evaluation, we identified scales defined as
'Recommended' for the assessment of all forms of hyperkinetic disorders. The
situation highlighted by our analysis varies considerably, with several
'Recommended' scales being available for some conditions such as tics or
dystonia, but only one being available for myoclonus. This gap needs to be filled
by the scientific community through both the development of new clinical tools
and there finement of existing ones.
PMID- 26428310
TI - The characteristics of camptocormia in patients with Parkinson's disease: A large
cross-sectional multicenter study in Japan.
AB - PURPOSE: The goal of the present study was to clarify the clinical
characteristics and laboratory results of parkinsonian symptoms among patients
with and without camptocormia. METHODS: Seventy-eight Parkinson's disease (PD)
patients with camptocormia and 78 PD patients without camptocormia underwent a
neurological examination, a blood test, and spinal magnetic resonance imaging
(MRI). PD with camptocormia group and PD with non-camptocormia group were matched
on age, age at PD onset, and sex. PRINCIPAL RESULTS: Camptocormia group had
significantly higher prevalence of compression fractures, more severe
parkinsonian symptoms, and a greater incidence of dementia than those without
camptocormia. Serum creatine kinase levels in camptocormia group significantly
elevated compared with non-camptocormia group. There were higher prevalence of
abnormal findings in spine MRI including compression fractures and paravertebral
muscle changes in camptocormia group compared with non-camptocormia group. MAJOR
CONCLUSIONS: Camptocormia is associated with a greater prevalence of compression
fractures and associated with greater UPDRS part II, part III score, axial score,
and lower MMSE in this cross-sectional study. Thus, it can be concluded that
camptocormia in PD is predominantly myopathic.
PMID- 26428311
TI - Palmaris brevis spasm: Identified by high resolution ultrasound and treated by
botulinum toxin.
PMID- 26428312
TI - Endothelial nitric oxide synthase: From biochemistry and gene structure to
clinical implications of NOS3 polymorphisms.
AB - Nitric oxide (NO) is an important vasodilator with a well-established role in
cardiovascular homeostasis. While mediator is synthesized from L-arginine by
neuronal, endothelial, and inducible nitric oxide synthases (NOS1,NOS3 and NOS2
respectively), NOS3 is the most important isoform for NO formation in the
cardiovascular system. NOS3 is a dimeric enzyme whose expression and activity are
regulated at transcriptional, posttranscriptional,and posttranslational levels.
The NOS3 gene, which encodes NOS3, exhibits a number of polymorphic sites
including single nucleotide polymorphisms (SNPs), variable number of tandem
repeats (VNTRs), microsatellites, and insertions/deletions. Some NOS3
polymorphisms show functional effects on NOS3 expression or activity, thereby
affecting NO formation. Interestingly, many studies have evaluated the effects of
functional NOS3 polymorphisms on disease susceptibility and drug responses.
Moreover, some studies have investigated how NOS3 haplotypes may impact
endogenous NO formation and disease susceptibility. In this article,we carried
out a comprehensive review to provide a basic understanding of biochemical
mechanisms involved in NOS3 regulation and how genetic variations in NOS3 may
translate into relevant clinical and pharmacogenetic implications.
PMID- 26428313
TI - Reference gene selection for quantitative gene expression studies during
biological invasions: A test on multiple genes and tissues in a model ascidian
Ciona savignyi.
AB - As invasive species have successfully colonized a wide range of dramatically
different local environments, they offer a good opportunity to study interactions
between species and rapidly changing environments. Gene expression represents one
of the primary and crucial mechanisms for rapid adaptation to local environments.
Here, we aim to select reference genes for quantitative gene expression analysis
based on quantitative Real-Time PCR (qRT-PCR) for a model invasive ascidian,
Ciona savignyi. We analyzed the stability of ten candidate reference genes in
three tissues (siphon, pharynx and intestine) under two key environmental
stresses (temperature and salinity) in the marine realm based on three programs
(geNorm, NormFinder and delta Ct method). Our results demonstrated only minor
difference for stability rankings among the three methods. The use of different
single reference gene might influence the data interpretation, while multiple
reference genes could minimize possible errors. Therefore, reference gene
combinations were recommended for different tissues - the optimal reference gene
combination for siphon was RPS15 and RPL17 under temperature stress, and RPL17,
UBQ and TubA under salinity treatment; for pharynx, TubB, TubA and RPL17 were the
most stable genes under temperature stress, while TubB, TubA and UBQ were the
best under salinity stress; for intestine, UBQ, RPS15 and RPL17 were the most
reliable reference genes under both treatments. Our results suggest that the
necessity of selection and test of reference genes for different tissues under
varying environmental stresses. The results obtained here are expected to reveal
mechanisms of gene expression-mediated invasion success using C. savignyi as a
model species.
PMID- 26428314
TI - Problem Management Plus (PM+) for common mental disorders in a humanitarian
setting in Pakistan; study protocol for a randomised controlled trial (RCT).
AB - BACKGROUND: In humanitarian settings common mental disorders (depression, anxiety
disorders, posttraumatic stress disorder) are highly prevalent. The World Health
Organization (WHO) has developed Problem Management Plus (PM+), a 5-session,
individual psychological intervention program, delivered by paraprofessionals
that addresses common mental disorders in people in communities affected by
adversity. The objectives of this study are to test effectiveness and cost
effectiveness of the locally adapted PM+ compared to Treatment as usual (TAU) in
Peshawar District, Pakistan. METHODS: A randomised controlled trial will be
conducted in 346 primary care attendees in 3 health care centres in Peshawar
District, Pakistan. After informed consent, primary care attendees with high
levels of psychological distress according to the General Health Questionnaire-12
(GHQ-12) and functional impairment (WHO Disability Assessment Schedule 2.0
(WHODAS)) will be assigned to PM+ (n = 173) or TAU (n = 173). At baseline, 1 week
and 3 months following PM+, independent assessors will assess psychological
distress with the Hospital Anxiety and Depression Scale (HADS), and functional
disability with the WHODAS. Secondary outcomes are posttraumatic stress disorder
(PTSD) symptoms, and client-perceived priority problems. Further, cost
effectiveness will be assessed using the Service Receipt Inventory (SRI).
DISCUSSION: If proven effective, PM+ will be rolled out to other areas for
further adaptation and testing in diverse humanitarian settings. TRIAL
REGISTRATION: ACTRN12614001235695. Registered 26 November 2014. Australian New
Zealand Clinical Trials Registry.
PMID- 26428315
TI - Mechanisms underpinning the peak knee flexion moment increase over 2-years
following arthroscopic partial meniscectomy.
AB - BACKGROUND: Knee osteoarthritis is common in people who have undergone partial
meniscectomy, and a higher external knee flexion moment during gait may be a
potential contributor. Although the peak external knee flexion moment has been
shown to increase from 3 months to 2 years following partial meniscectomy,
mechanisms underpinning the increase in the peak knee flexion moment are unknown.
METHODS: Sixty-six participants with partial meniscectomy completed three
dimensional gait (normal and fast pace) and quadriceps strength assessment at
baseline (3 months following partial meniscectomy) and again 2 years later.
Variables included external knee flexion moment, vertical ground reaction force,
knee flexion kinematics, and quadriceps peak torque. FINDINGS: For normal pace
walking, the main significant predictors of change in peak knee flexion moment
were an increase in peak vertical ground reaction force (R(2)=0.55), mostly due
to an increase in walking speed, and increase in peak knee flexion angle
(R(2)=0.19). For fast pace walking, the main significant predictors of change in
peak knee flexion moment were an in increase in peak vertical ground reaction
force (R(2)=0.51) and increase in knee flexion angle at initial contact
(R(2)=0.17). Change in peak vertical force was mostly due to an increase in
walking speed. INTERPRETATION: Findings suggest that increases in vertical ground
reaction force and peak knee flexion angle during stance are predominant
contributors to the 2-year change in peak knee flexion moment. Future studies are
necessary to refine our understanding of joint loading and its determinants
following meniscectomy.
PMID- 26428316
TI - A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal
tumors.
AB - Sertoli-Leydig cell tumors are characterized by the presence of somatic DICER1
hotspot mutations. In this study, we sought to define the association between
DICER1 hotspot mutations and different morphologic subtypes of ovarian Sertoli
Leydig cell tumors. Furthermore, we aimed to assess whether DICER1 hotspot
mutations occur in other ovarian sex cord-stromal tumors, testicular sex cord
stromal tumors, or other female genital tract tumors with rhabdomyosarcomatous
differentiation. We subjected a series of ovarian Sertoli-Leydig cell tumors
(n=32), Sertoli cell tumors (n=5) and gynandroblastomas (n=5), testicular sex
cord-stromal tumors (n=15) and a diverse group of female genital tract tumors
with rhabdomyosarcomatous morphology (n=10) to DICER1 hotspot mutation analysis
using Sanger sequencing. We also tested two gynandroblastomas for the presence of
FOXL2 hotspot mutations (p.C134W; c.402C>G). Twenty of 32 (63%) Sertoli-Leydig
cell tumors harbored a DICER1 hotspot mutation, of which 80% had the p.E1705K
mutation. No association was found between DICER1 mutation status and the
presence of heterologous or retiform differentiation in Sertoli-Leydig cell
tumors. DICER1 mutations were found at similar frequencies in gynandroblastoma
(2/5; 40%) and ovarian Sertoli cell tumors (5/8; 63%; P>0.1), and all mutated
tumors harbored a p.E1705K mutation. DICER1 hotspot mutations were also
identified in a single cervical rhabdomyosarcoma and in the rhabdomyosarcomatous
component of a uterine carcinosarcoma. No DICER1 mutations were detected in
testicular sex cord-stromal tumors. Two DICER1 wild-type gynandroblastomas
harbored a p.C134W FOXL2 hotspot mutation in both tumor components. In this study
we confirmed that DICER1 hotspot mutations occur in over half of ovarian Sertoli
Leydig cell tumors, and are unrelated to tumor differentiation. We also widened
the spectrum of ovarian sex cord-stromal tumors with sertoliform differentiation,
in which DICER1 mutations are known to occur, to include Sertoli cell tumors and
gynandroblastomas. Our results suggest that DICER1 mutations may not have a role
in testicular sex cord-stromal tumorigenesis.
PMID- 26428317
TI - Comprehensive screening of alternative lengthening of telomeres phenotype and
loss of ATRX expression in sarcomas.
AB - According to cytogenetic aberrations, sarcomas can be categorized as complex or
simple karyotype tumors. Alternative lengthening of telomeres is a telomere
maintenance mechanism common in sarcomas. Recently, this mechanism was found to
be associated with loss of either alpha-thalassemia/mental retardation syndrome X
linked (ATRX) or death domain-associated (DAXX) protein. We previously reported
that alternative lengthening of telomeres and loss of ATRX expression were common
in leiomyosarcoma, angiosarcoma, pleomorphic liposarcoma, and dedifferentiated
liposarcoma. In the present study, we screened an additional 245 sarcomas of
other types to determine the prevalence of alternative lengthening of telomeres,
loss of ATRX/DAXX expression, and their relationship. Undifferentiated
pleomorphic sarcomas were frequently alternative lengthening of telomeres
positive (65%) and loss of ATRX was seen in approximately half of the alternative
lengthening of telomeres-positive tumors. Nineteen of 25 myxofibrosarcomas were
alternative lengthening of telomeres-positive, but only one was ATRX deficient.
Three of 15 radiation-associated sarcomas were alternative lengthening of
telomeres positive, but none of them was ATRX deficient. Alternative lengthening
of telomeres and/or loss of ATRX were uncommon in malignant peripheral nerve
sheath tumors, gastrointestinal stromal tumors, and embryonal rhabdomyosarcomas.
By contrast, none of the 71 gene fusion-associated sarcomas was ATRX deficient or
alternative lengthening of telomeres positive. All tumors exhibited preserved
DAXX expression. Combining our previous studies and this study, a total of 384
sarcomas with complex karyotypes were examined, 83 of which were ATRX deficient
(22%). By telomere-specific fluorescence in situ hybridization, 45% (138/308)
were alternative lengthening of telomeres positive, 55% (76/138) of which were
ATRX deficient. Loss of ATRX was highly associated with alternative lengthening
of telomeres (P<0.001). We conclude that alternative lengthening of telomeres is
a frequent telomere-maintenance mechanism in cytogenetically complex sarcomas.
Loss of ATRX is highly associated with this feature.
PMID- 26428318
TI - Mitochondrial DNA mutations distinguish bilateral multifocal renal oncocytomas
from familial Birt-Hogg-Dube tumors.
AB - Oncocytomas are mostly benign tumors characterized by accumulation of defective
mitochondria, and in sporadic cases, are associated with disruptive mitochondrial
DNA (mtDNA) mutations. However, the role mtDNA mutations have in renal tumors of
Birt-Hogg-Dube (BHD) patients and other renal oncocytomas with an apparent
genetic component has not been investigated to date. Here we characterize the
mitochondrial genome in different renal tumors and investigate the possibility of
employing mtDNA sequencing analyses of biopsy specimens to aid in the
differential diagnosis of oncocytomas. The entire mitochondrial genome was
sequenced in 25 samples of bilateral and multifocal (BMF) renal oncocytomas, 30
renal tumors from BHD patients and 36 non-oncocytic renal tumors of different
histologies as well as in biopsy samples of kidney tumors. mtDNA sequencing in
BMF oncocytomas revealed that all tumors carry disruptive mutations, which impair
the assembly of the NADH-ubiquinone oxidoreductase. Multiple tumors from a given
BMF oncocytoma patient mainly harbor the same somatic mutation and the kidneys of
these patients display diffuse oncocytosis. In contrast, renal oncocytomas of
patients with BHD syndrome and renal tumors with different histologies do not
show disruptive mtDNA mutations. Moreover, we demonstrate that it is feasible to
amplify and sequence the entire mtDNA in biopsy specimens, and that these
sequences are representative of the tumor DNA. These results show that pathogenic
mtDNA mutations affecting complex I of the respiratory chain are strongly
correlated with the oncocytoma phenotype in non-BHD-related renal tumors and that
mtDNA sequences from biopsies are predictive of the tumor genotype. This work
supports a role for mtDNA mutations in respiratory chain complexes as diagnostic
markers for renal oncocytomas.
PMID- 26428319
TI - Combined Hydroxyurea and Verapamil in the Clinical Treatment of Refractory
Meningioma: Human and Orthotopic Xenograft Studies.
AB - OBJECTIVE: Previous in vitro and in vivo results suggested that hydroxyurea (HU)
and verapamil could suppress meningioma growth individually and synergistically.
We evaluated the clinical efficacy and safety of this approach for the treatment
of refractory recurrent/progressive meningiomas and expanded our studies in a
xenograft orthotopic mouse model. METHODS: Six women and 1 man, aged 26-76 years
(median, 56 years), with magnetic resonance imaging-proven progression of >= 25%
in cross-sectional area of recurrent meningioma (2 World Health Organization
grade I, 5 grade II) within the preceding 6 months received HU 1000 or 1500
mg/day (20 mg/kg/day, twice daily) as well as verapamil sustained-release tablets
with dose escalation every 2 weeks (120-240 mg/day). They underwent magnetic
resonance imaging every 3 months during therapy. To augment the clinical trial
results, we performed mouse orthotopic xenograft experiments using similar dosing
to test tumor growth, vascularity, and drug bioavailability. RESULTS: After a
mean of 8.1 cycles of treatment, the patients demonstrated no significant
radiographic responses during mean follow-up of 14.5 +/- 4.8 months. Median
progression-free survival (PFS) was 8.0 months, and 6-month PFS was 85%. Side
effects occurred in 6 (86%) patients. Xenograft studies showed no effect of
individual or combined treatments on meningioma growth. Neither HU nor verapamil
was detectable in mouse brain tumor tissue despite adequate serum levels within
therapeutic ranges. CONCLUSIONS: Our results showed no effect of HU or verapamil
on tumor recurrence, PFS, and in vivo tumor burden reduction. Drug delivery to
the tumor may be a major limitation.
PMID- 26428320
TI - Intradural Spinal Arachnoid Cyst: A Long-Term Postlaminectomy Complication: A
Case Report and Review of the Literature.
AB - BACKGROUND: Spinal arachnoid cysts are a rare cause of spinal cord compression.
Intradural arachnoid cysts are rarer than extradural arachnoid cysts. Spinal
arachnoid cysts are mostly congenital in origin. Arachnoid cysts due to trauma,
lumbar puncture, or surgery are rarely reported. Most arachnoid cysts are located
posterior to the spinal cord in the thoracic regions. The ideal treatment is
laminectomy or laminoplasty with puncture, marsupialization, or excision. But the
development of a cervico-thoracic spinal intradural extramedullary arachnoid cyst
anteriorly located 28 years after laminectomy is a recognizable complication of
laminectomy. CASE DESCRIPTION: We report here a case of a 45-year-old man who
underwent C6-T1 laminectomy at the age of 17 years for cervical intervertebral
disc prolapse (C6/7, C7/T1) and compressive myelopathy. Twenty-eight years after
laminectomy, he developed spastic quadriparesis and was diagnosed with a spinal
intradural extramedullary anterior arachnoid cyst at the laminectomy site with
compressive myelopathy. CONCLUSIONS: So, although laminectomy with excision is
usually practiced to treat spinal arachnoid cysts, laminectomy itself is a cause
of development of intradural arachnoid cysts.
PMID- 26428321
TI - Near-Complete Resolution of Clinical and Radiographic Findings After Endovascular
Embolization of a Giant Serpentine A1 Aneurysm.
AB - BACKGROUND: Giant serpentine aneurysms are complex intracranial lesions,
associated with a poor prognosis if left untreated. Treatment usually involves
surgical trapping of the aneurysm with arterio-arterial anastomosis; however,
recent endovascular management has been implemented for the management of such
aneurysms. CASE DESCRIPTION: We report the unique case of a 71-year-old woman who
presented with visual deficits due to the mass effect of a giant serpentine
aneurysm arising from the A1 segment of the anterior cerebral artery. Because of
its location proximal to a widely patent anterior communicating artery,
angiographic cure was achieved with sacrifice of the A1 segment. Clinical and
radiographic follow-up demonstrated resolution of the presenting symptoms and
near-complete obliteration of the aneurysm. CONCLUSIONS: Thrombosed giant
serpentine aneurysms can show dramatic resolution of mass effect with
endovascular treatment.
PMID- 26428322
TI - Predictors of Shunt-Dependent Hydrocephalus Following Aneurysmal Subarachnoid
Hemorrhage.
AB - BACKGROUND: Shunt-dependent hydrocephalus is a common complication of aneurysmal
subarachnoid hemorrhage (aSAH). There is a need to identify patients who require
ventriculoperitoneal shunt (VPS) insertion so that any modifiable risk factors
can be addressed early after aSAH. METHODS: Exploratory analysis was performed on
413 patients enrolled in CONSCIOUS-1, a prospective randomized controlled trial
of patients with aSAH treated with clazosentan. The association between clinical
and neuroimaging covariates and VPS placement was first determined by univariate
analysis. Covariates with P < 0.15 on univariate analysis were then analyzed in a
multivariate logistic regression model. Receiver operating characteristic curve
analysis was used to define optimal predictive thresholds. The published
literature was reviewed to determine the overall rate of VPS insertion after
aSAH. RESULTS: Overall, 17.2% (71/413) of patients required VPS insertion.
Multivariate analysis demonstrated that insertion of an external ventricular
drain (odds ratio, 6.21; 95% confidence interval, 2.51-16.91) and increasing
volume of cerebrospinal fluid (CSF) drainage per day (odds ratio, 1.004; 95%
confidence interval, 1.000-1.009) were associated with VPS insertion. Receiver
operating characteristic curve analysis revealed an optimal daily CSF output
threshold of 78 mL was predictive of VPS insertion. Among 41,789 patients with
aSAH from 66 published studies, the overall VPS insertion rate was 12.7%.
CONCLUSIONS: The presence of an external ventricular drain and increased daily
CSF output (above 78 mL/day) seems to be predictive of subsequent VPS insertion
after aSAH. Although we could not identify modifiable risk factors for needing a
VPS, nevertheless, these findings identify patients at greatest risk of VPS
placement and inform treatment decisions as well as patient expectations.
PMID- 26428323
TI - Neuroprotective Effects of Thymoquinone on the Hippocampus in a Rat Model of
Traumatic Brain Injury.
AB - BACKGROUND: Traumatic brain injury is a leading cause of morbidity and mortality
worldwide. We evaluated the neuroprotective effects of thymoquinone (TQ) in a rat
model of traumatic brain injury by using biochemical and histopathologic methods
for the first time. MATERIALS AND METHODS: Twenty-four rats were divided into
sham (n = 8), trauma (n = 8), and TQ-treated (n = 8) groups. A moderate degree of
head trauma was induced with the use of Feeney's falling weight technique, and TQ
(5 mg/kg/day) was administered to the TQ-treated group for 7 days. All animals
were killed after cardiac perfusion. Brain tissues were extracted immediately
after perfusion without damaging the tissues. Biochemical procedures were
performed with the serum, and a histopathologic evaluation was performed on the
brain tissues. Biochemical experiments included malondialdehyde (MDA), reduced
and oxidized coenzyme Q10 analysis, DNA isolation and hydroylazation, and
glutathione peroxidase, and superoxide dismutase analyses. RESULTS: Neuron
density in contralateral hippocampal regions (CA1, CA2-3, and CA4) 7 days after
the trauma decreased significantly in the trauma and TQ-treated groups, compared
with that in the control group. Neuron densities in contralateral hippocampal
regions (CA1, CA2-3, and CA4) were greater in the TQ-treated group than in the
trauma group. TQ did not increase superoxide dismutase or glutathione peroxidase
antioxidant levels. However, TQ decreased the MDA levels. CONCLUSIONS: These
results indicate that TQ has a healing effect on neural cells after head injury
and this effect is mediated by decreasing MDA levels in the nuclei and
mitochondrial membrane of neurons.
PMID- 26428324
TI - A 5-Year Retrospective Analysis of Exposure to Ionizing Radiation by Neurosurgery
Residents in the Modern Era.
AB - BACKGROUND: The potential for radiation exposure during neurosurgical training
has increased dramatically in the last decade. Incorporation of instrumented and
minimally invasive spinal surgery and neuroendovascular procedures into the
curriculum has led to increased potential for exposure to ionizing radiation.
Contemporary neurosurgery residents' exposure to radiation has not been
previously reported. OBJECTIVE: To determine neurosurgery residents' exposure to
radiation over the course of 7 years of training. METHODS: Retrospective analysis
of a prospectively maintained radiation database from July 2009 to July 2014 for
all neurosurgery residents based on radiation dosimetry data. Standard radiation
safety precautions were used (e.g., lead gowns or aprons), although compliance
was not specifically monitored. RESULTS: Thirty-eight neurosurgery residents were
monitored from 2009 to 2014. Radiation exposure data were available for 34
residents for the final analysis. A total of 20,541 days of radiation monitoring
data were available. The mean deep dose equivalent over this period was 0.67 +/-
0.75 mrem per resident/day. The calculated maximum cumulative exposure during the
course of residency training was 12.15 +/- 13.50 mSv, approximately equivalent to
6 computed tomography head scans. CONCLUSIONS: To our knowledge, this study is
the first to quantify radiation exposure for neurosurgery residents in the
current era of training. From this work, efforts may be initiated to increase
awareness and safety with regard to radiation exposure. Although the total dose
is not high, a better understanding of the impact of radiation exposure on
practitioners may help to drive institutional policies to reduce occupational
exposure.
PMID- 26428325
TI - Experimental Evaluation of the Developmental Mechanism Underlying Fractures at
the Adjacent Segment.
AB - BACKGROUND: Compression fractures at adjacent mobile segments have been reported
as adjacent segment disease under trauma in several studies. In this study, the
occurrence of fractures at the adjacent segment was evaluated experimentally
under trauma. METHODS: Static testing of different fixation systems was performed
to show their biomechanical performances. The ovine vertebrae fixed with rigid,
dynamic, and semirigid systems were used as test samples. The stiffness values of
the systems were obtained by testing the vertebrectomy models under compression
bending, lateral bending, and torsion tests. In addition, their effects on the
adjacent segments were experimentally evaluated within a drop mechanism. A free
fall drop mechanism was designed and manufactured. Next, 3.5-kg, 5-kg, and 7-kg
weights were released from 1 m above the test samples to generate compression
fractures. The occurrence of compression fractures was observed with the use of
radiograph of test samples, which were obtained before and after the drop test.
RESULTS: Dynamic and semirigid systems have advantages compared with rigid
systems as the result of their lower stiffness values. Radiographs showed that
epiphysis fractures occurred at fixed and adjacent mobile segments, which were
fixed with semirigid fixation. In addition, dynamic fixation well preserved the
fixed and adjacent mobile segments under trauma. CONCLUSIONS: The dynamic system
with a polyetheretherketone rod can better preserve both adjacent and fixed
segments. However, because of the cantilever beam effect, the semirigid system
exhibits a great disadvantage.
PMID- 26428326
TI - Outcome of Surgery for Idiopathic Normal Pressure Hydrocephalus: Role of
Preoperative Static and Pulsatile Intracranial Pressure.
AB - OBJECTIVES: To examine the outcome of surgery for idiopathic normal-pressure
hydrocephalus (iNPH) and how outcome relates to the preoperative static and
pulsatile intracranial pressure (ICP). METHODS: An observational cohort study
included all patients with iNPH managed at our department during the years 2002
2012 in whom overnight ICP monitoring was part of the preoperative work-up.
Clinical data were retrieved from a quality registry and ICP scores from a
pressure database. RESULTS: The study included 472 patients, 316 in the surgery
group and 156 in the nonsurgery group. Among those treated surgically, 278 (90%)
showed clinical improvement (Responders) whereas 32 (10%) had no improvement
(Nonresponders). Among Responders, only about one third reached the best clinical
scores; moreover, the difference in clinical score between Responders and
Nonresponders declined with time after surgery, particularly after 3-4 years. The
surgery was accompanied by acute intracranial hematomas in 11 patients (3.5%), of
whom 4 (1.3%) died. Survival (age at death) was significantly greater among the
Responders than in Nonresponders. Although the static ICP was normal in all
patients, the pulsatile ICP was significantly greater in Responders than in Non
responders. CONCLUSIONS: The pulsatile ICP was greater in shunt Responders than
Nonresponders. Although the clinical improvement declined over time and the
majority did not experience complete relief of symptoms, shunt Responders lived
significantly longer than Nonresponders. The present observations suggest that
the current surgical treatment regimens for iNPH (primarily shunt surgery)
address only some aspects of the disease process, in particular the aspect of
brain water disturbance.
PMID- 26428327
TI - Carotid Artery Stenosis in the Setting of Transcatheter Aortic Valve Replacement:
Clinical and Technical Considerations of Carotid Stenting.
AB - OBJECTIVE: No consensus exists regarding the safety and efficacy of treatment of
carotid stenosis before transcatheter aortic valve replacement (TAVR). Our
objective was to review our series of patients treated for carotid stenosis with
stenting in the setting of severe aortic valve disease and TAVR to evaluate its
safety and efficacy. METHODS: We reviewed patients who underwent carotid stenting
in the setting of preoperative work-up or after TAVR from August 2012 through
January 2015. Perioperative patient outcomes were collected to assess the safety
and efficacy of carotid stenting. RESULTS: Five patients (4 men, 1 woman; median
age, 83 years; range, 72-88 years) underwent successful carotid stenting before
(median, 30 days before; range, 2 days-3 months) TAVR. The median extent of
carotid stenosis was 80% (range, 75%-90%), but the diagnoses were incidental and
all patients were asymptomatic. One patient suffered acute systolic heart failure
during stenting requiring emergent balloon aortic valvuloplasty and vasopressor
therapy. Median intensive care unit stay was 1 day (range, 1-16 days) for all
patients, and 1 day for patients treated electively. The median hospital stay was
1 day (range, 1-16 days) for all patients, and 1 day for patients treated
electively. All patients were discharged home. None suffered immediate or delayed
neurological complications. CONCLUSIONS: We successfully performed carotid
stenting in 5 patients before TAVR for severe aortic pathology. These patients
require intensive care and careful monitoring. Larger prospective studies are
needed to determine whether carotid stenting in the setting of TAVR can provide
long-term neurological benefits.
PMID- 26428328
TI - Technical Advances in Aneurysm Surgery: Continuous Evolution and Patient
Selection Are the Key for Better Outcomes.
PMID- 26428329
TI - Screening for the metabolic side effects of antipsychotic medication: findings of
a 6-year quality improvement programme in the UK.
AB - OBJECTIVES: To increase the frequency and quality of screening for the metabolic
syndrome in people prescribed continuing antipsychotic medication. DESIGN: An
audit-based, quality improvement programme (QIP) with customised feedback to
participating mental health services after each audit, including benchmarked data
on their relative and absolute performance against an evidence-based practice
standard and the provision of bespoke change interventions. SETTING: Adult,
assertive outreach, community psychiatric services in the UK. PARTICIPANTS: 6
audits were conducted between 2006 and 2012. 21 mental health Trusts participated
in the baseline audit in 2006, submitting data on screening for 1966 patients,
while 32 Trusts participated in the 2012 audit, submitting data on 1591 patients.
RESULTS: Over the 6 years of the programme, there was a statistically significant
increase in the proportion of patients for whom measures for all 4 aspects of the
metabolic syndrome had been documented in the clinical records in the previous
year, from just over 1 in 10 patients in 2006 to just over 1 in 3 by 2012. The
proportion of patients with no evidence of any screening fell from almost 1/2 to
1 in 7 patients over the same period. CONCLUSIONS: The findings suggest that
audit-based QIPs can help improve clinical practice in relation to physical
healthcare screening. Nevertheless, they also reveal that only a minority of
community psychiatric patients prescribed antipsychotic medication is screened
for the metabolic syndrome in accordance with best practice recommendations, and
therefore potentially remediable causes of poor physical health remain undetected
and untreated.
PMID- 26428330
TI - Minimally important difference estimates and methods: a protocol.
AB - INTRODUCTION: Patient-reported outcomes (PROs) are often the outcomes of greatest
importance to patients. The minimally important difference (MID) provides a
measure of the smallest change in the PRO that patients perceive as important. An
anchor-based approach is the most appropriate method for MID determination. No
study or database currently exists that provides all anchor-based MIDs associated
with PRO instruments; nor are there any accepted standards for appraising the
credibility of MID estimates. Our objectives are to complete a systematic survey
of the literature to collect and characterise published anchor-based MIDs
associated with PRO instruments used in evaluating the effects of interventions
on chronic medical and psychiatric conditions and to assess their credibility.
METHODS AND ANALYSIS: We will search MEDLINE, EMBASE and PsycINFO (1989 to
present) to identify studies addressing methods to estimate anchor-based MIDs of
target PRO instruments or reporting empirical ascertainment of anchor-based MIDs.
Teams of two reviewers will screen titles and abstracts, review full texts of
citations, and extract relevant data. On the basis of findings from studies
addressing methods to estimate anchor-based MIDs, we will summarise the available
methods and develop an instrument addressing the credibility of empirically
ascertained MIDs. We will evaluate the credibility of all studies reporting on
the empirical ascertainment of anchor-based MIDs using the credibility
instrument, and assess the instrument's inter-rater reliability. We will
separately present reports for adult and paediatric populations. ETHICS AND
DISSEMINATION: No research ethics approval was required as we will be using
aggregate data from published studies. Our work will summarise anchor-based
methods available to establish MIDs, provide an instrument to assess the
credibility of available MIDs, determine the reliability of that instrument, and
provide a comprehensive compendium of published anchor-based MIDs associated with
PRO instruments which will help improve the interpretability of outcome effects
in systematic reviews and practice guidelines.
PMID- 26428331
TI - General practitioners' attitudes towards the management of dental conditions and
use of antibiotics in these consultations: a qualitative study.
AB - OBJECTIVES: This study aimed to produce an account of the attitudes of general
practitioners (GPs) towards the management of dental conditions in general
practice, and sought to explore how GPs use antibiotics in the treatment of
dental problems. DESIGN: Qualitative study employing semistructured telephone
interviews and thematic analysis. PARTICIPANTS: 17 purposively sampled GPs
working in Wales, of which 9 were male. The median number of years since
graduation was 21. Maximum variation sampling techniques were used to ensure
participants represented different Rural-Urban localities, worked in communities
with varying levels of deprivation, and had differing lengths of practising
career. RESULTS: Most GPs reported regularly managing dental problems, with more
socioeconomically deprived patients being particularly prone to consult.
Participants recognised that dental problems are not optimally managed in general
practice, but had sympathy with patients experiencing dental pain who reported
difficulty obtaining an emergency dental consultation. Many GPs considered
antibiotics an acceptable first-line treatment for acute dental problems and
reported that patients often attended expecting to receive antibiotics. GPs who
reported that their usual practice was to prescribe antibiotics were more likely
to prioritise patients' immediate needs, whereas clinicians who reported rarely
prescribing often did so to encourage patients to consult a dental professional.
CONCLUSIONS: The presentation of patients with dental problems presents
challenges to GPs who report concerns about their ability to manage such
conditions. Despite this, many reported frequently prescribing antibiotics for
patients with dental conditions. This may contribute to both patient morbidity
and the emergence of antimicrobial resistance. This research has identified the
need for quantitative data on general practice consultations for dental problems
and qualitative research exploring patient perspectives on reasons for
consulting. The findings of these studies will inform the design of an
intervention to support patients in accessing appropriate care when experiencing
dental problems.
PMID- 26428332
TI - The UK Out of Hospital Cardiac Arrest Outcome (OHCAO) project.
AB - INTRODUCTION: Reducing premature death is a key priority for the UK National
Health Service (NHS). NHS Ambulance services treat approximately 30 000 cases of
suspected cardiac arrest each year but survival rates vary. The British Heart
Foundation and Resuscitation Council (UK) have funded a structured research
programme--the Out of Hospital Cardiac Arrest Outcomes (OHCAO) programme. The aim
of the project is to establish the epidemiology and outcome of OHCA, explore
sources of variation in outcome and establish the feasibility of setting up a
national OHCA registry. METHODS AND ANALYSIS: This is a prospective observational
study set in UK NHS Ambulance Services. The target population will be adults and
children sustaining an OHCA who are attended by an NHS ambulance emergency
response and where resuscitation is attempted. The data collected will be
characterised broadly as system characteristics, emergency medical services (EMS)
dispatch characteristics, patient characteristics and EMS process variables. The
main outcome variables of interest will be return of spontaneous circulation and
medium-long-term survival (30 days to 10-year survival). ETHICS AND
DISSEMINATION: Ethics committee permissions were gained and the study also has
received approval from the Confidentiality Advisory Group Ethics and
Confidentiality committee which provides authorisation to lawfully hold
identifiable data on patients without their consent. To identify the key
characteristics contributing to better outcomes in some ambulance services,
reliable and reproducible systems need to be established for collecting data on
OHCA in the UK. Reports generated from the registry will focus on data
completeness, timeliness and quality. Subsequent reports will summarise
demographic, patient, process and outcome variables with aim of improving patient
care through focus quality improvement initiatives.
PMID- 26428334
TI - An unusual presentation of acute Q fever.
PMID- 26428333
TI - Effectiveness of multicomponent interventions in primary healthcare settings to
promote continuous smoking cessation in adults: a systematic review.
AB - OBJECTIVE: The objective of the present review is to evaluate
multicomponent/complex primary care (PC) interventions for their effectiveness in
continuous smoking abstinence by adult smokers. DESIGN: A systematic review of
randomised and non-randomised controlled trials was undertaken. ELIGIBILITY
CRITERIA FOR INCLUDED STUDIES: Selected studies met the following criteria:
evaluated effects of a multicomponent/complex intervention (with 2 or more
intervention components) in achieving at least 6-month abstinence in adult
smokers who visited a PC, biochemical confirmation of abstinence, intention-to
treat analysis and results published in English/Spanish. METHODS: We followed
PRISMA statement to report the review. We searched the following data sources:
MEDLINE, Web of Science, Scopus (from inception to February 2014), 3 key journals
and a tobacco research bulletin. The Scottish Intercollegiate Guidelines Network
checklists were used to evaluate methodological quality. Data selection,
evaluation and extraction were done independently, using a paired review
approach. Owing to the heterogeneity of interventions in the studies included, a
meta-analysis was not conducted. RESULTS: Of 1147 references identified, 9
studies were selected (10,204 participants, up to 48 months of follow-up,
acceptable methodological quality). Methodologies used were mainly individual or
group sessions, telephone conversations, brochures or quit-smoking kits,
medications and economic incentives for doctors and no-cost medications for
smokers. Complex interventions achieved long-term continuous abstinence ranging
from 7% to 40%. Behavioural interventions were effective and had a dose-response
effect. Both nicotine replacement and bupropion therapy were safe and effective,
with no observed differences. CONCLUSIONS: Multicomponent/complex interventions
in PC are effective and safe, appearing to achieve greater long-term continuous
smoking cessation than usual care and counselling alone. Selected studies were
heterogeneous and some had significant losses to follow-up. Our results show that
smoking interventions should include more than one component and a strong follow
up of the patient to maximise results.
PMID- 26428336
TI - Researching and preventing diagnostic errors: chasing patient safety from a
different angle.
PMID- 26428335
TI - Clinical development of cancer therapeutics that target metabolism.
AB - Glucose and glutamine metabolism in cancer cells are markedly elevated relative
to non-transformed normal cells. This metabolic reprogramming enables the
production of adenosine triphosphate and the anabolic precursors needed for
survival, growth and motility. The recent observations that mutant oncogenic
proteins and the loss of tumor suppressors activate key metabolic enzymes suggest
that selective inhibition of these enzymes may yield effective cancer
therapeutics with acceptable toxicities. In support of this concept, pre-clinical
studies of small molecule antagonists of several metabolic enzymes in tumor
bearing mice have demonstrated reasonable therapeutic indices. We will review the
rationale for targeting metabolic enzymes as a strategy to treat cancer and will
detail the results of several recent clinical trials of metabolic inhibitors in
advanced cancer patients.
PMID- 26428337
TI - The ethical dilemma posed by unmonitored new anticoagulants.
PMID- 26428338
TI - Unusual cause of pleural effusion: ovarian hyperstimulation syndrome.
PMID- 26428339
TI - Diffuse iris nevus.
PMID- 26428341
TI - You Want to Publish in the Journal of Professional Nursing: Here Are Some
Strategies for Success.
PMID- 26428342
TI - The Development of a Clinical Nurse Scholar in Baccalaureate Education.
AB - The purpose of this national study was to explore the vision of chief academic
officers for baccalaureate nursing education. We invited chief academic nursing
officers, randomly selected from a representative sample of accredited
baccalaureate nursing programs to participate in the study. Audiotaped interviews
were conducted in focus groups at professional meetings or by telephone and were
transcribed verbatim. Data collection continued until thematic saturation was
reached (N = 29). Analysis of the findings revealed themes that described future
vision for baccalaureate education that provides guidance to faculty as they
develop curriculum. An overarching theme "We are all Stewards of the Profession"
and three supporting themes emerged: "Learning Pathways are Varied," "Faculty
Need to Grow," and "New Pedagogies Need to Focus on the Development of 'Who I Am'
as a Clinical Scholar." Findings point to a future where diverse learning
pathways are integrated throughout the curriculum. The curriculum of tomorrow
will place greater emphasis on the development of professional identity as a
nurse and calls for expanded stewardship for nursing education. Deans recommended
that investing time and resources into well-designed faculty development programs
will help all faculty, regardless of appointment, to adapt to changing student
needs and rapidly evolving practice environments.
PMID- 26428343
TI - Collaboration Among DNP- and PhD-Prepared Nurses: Opportunity to Drive Positive
Change.
AB - Because of the rapidly changing environment of doctoral education, collaborative
relationships between doctor of nursing practice and doctor of philosophy
prepared nurses continue to evolve. Although there are few currently reportable
outcomes, examples are given of collaborative efforts highlighting scholarship,
education, practice, and research. In accordance with the Institute Of Medicine
recommendations and building upon work done by the American Association of
Colleges of Nursing, this article describes opportunities for expanding
collaboration among doctoral-prepared nurses. Collaboration facilitates a timely
translation of research into practice, enhances educational opportunities, drives
positive change, and improves health outcomes.
PMID- 26428344
TI - Community-Academic Partnerships: Developing a Service-Learning Framework.
AB - Academic partnerships with hospitals and health care agencies for authentic
clinical learning have become a major focus of schools of nursing and
professional nursing organizations. Formal academic partnerships in community
settings are less common despite evolving models of care delivery outside of
inpatient settings. Community-Academic partnerships are commonly developed as a
means to engage nursing students in service-learning experiences with an emphasis
on student outcomes. The benefit of service-learning projects on community
partners and populations receiving the service is largely unknown primarily due
to the lack of structure for identifying and measuring outcomes specific to
service-learning. Nursing students and their faculty engaged in service-learning
have a unique opportunity to collaborate with community partners to evaluate
benefits of service-learning projects on those receiving the service. This
article describes the development of a service-learning framework as a first step
toward successful measurement of the benefits of undergraduate nursing students'
service-learning projects on community agencies and the people they serve through
a collaborative community-academic partnership.
PMID- 26428345
TI - Joining Forces: Enriching RN-to-BSN Education With Veteran-Centered Experiences.
AB - This article highlights the commitment of the American Association of Colleges of
Nursing to engage nursing schools to support the Joining Forces initiative by
enhancing the education and preparation of the nation's nurses to care for
veterans, service members, and their families. The progress toward meeting the
Joining Forces pledge and integrating veteran-centered learning in an on-line
registered nurse-to-bachelor of science in nursing program is described.
PMID- 26428346
TI - Are Virtual Classrooms Colorblind?
AB - E-learning, increasingly employed in nursing education, has been embraced as a
means to enhance options for all students, particularly those with limited
educational opportunities. Although a desire to increase access for underserved
students is often cited, disparities in availability, usage, and quality of e
learning persist among diverse households and student populations when compared
to the general population. In this article, these issues will be examined along
with reflection on the extent to which culture has been integrated into on-line
design and instruction. Historical and cultural aspects, circumscribing virtual
classrooms, are discussed using African Americans as an exemplar. The imperative
to harness the democratizing potential of this educational format is underscored.
In this article, culture will be examined in light of the significant growth in
on-line nursing education over the past several decades.
PMID- 26428347
TI - Mental Snapshots: Creating an Organized Plan for Health Assessment.
AB - Beginning nursing students enter a rapidly moving and changing health care
climate. Multiple stimulations can frighten and overwhelm the student's ability
to find order of essential patient information. Students need to know how to
collect, process, and manage important health data accurately and efficiently in
the clinical setting. An integrative method for teaching nursing students to walk
into the patient's room and construct a patterned sequence of focused assessments
assists students in creating an organized plan for health assessment. The Mental
Snapshots Method includes three components for health assessment: (a) sequential
assessment steps of the patient; (b) color-coded visual images of the patient
representing a bodily condition; and (c) focused assessment questions of primary
health complaint(s) with a plan for nursing care. This mental snapshots strategy
employs an information processing model of sensory, memory, and motor
functioning, which enable students to maintain patient quality and safety.
PMID- 26428348
TI - The Effect of a Self-Reflection and Insight Program on the Nursing Competence of
Nursing Students: A Longitudinal Study.
AB - Nurses have to solve complex problems for their patients and their families, and
as such, nursing care capability has become a focus of attention. The aim of this
longitudinal study was to develop a self-reflection practice exercise program for
nursing students to be used during clinical practice and to evaluate the effects
of this program empirically and longitudinally on change in students' clinical
competence, self-reflection, stress, and perceived teaching quality. An
additional aim was to determine the predictors important to nursing competence.
We sampled 260 nursing students from a total of 377 practicum students to
participate in this study. A total of 245 students nurse completed 4
questionnaires, Holistic Nursing Competence Scale, Self-Reflection and Insight
Scale, Perceived Stress Scale, and Clinical Teaching Quality Scale, at 2, 4, and
6 months after clinical practice experience. Generalized estimating equation
models were used to examine the change in scores on each of the questionnaires.
The findings showed that, at 6 months after clinical practice, nursing competence
was significantly higher than at 2 and 4 months, was positively related to self
reflection and insight, and was negatively related to practice stress. Nursing
students' competence at each time period was positively related to clinical
teachers' instructional quality at 4 and 6 months. These results indicate that a
clinical practice program with self-reflection learning exercise improves nursing
students' clinical competence and that nursing students' self-reflection and
perceived practice stress affect their nursing competence. Nursing core
competencies are enhanced with a self-reflection program, which helps nursing
students to improve self-awareness and decrease stress that may interfere with
learning. Further, clinical practice experience, self-reflection and insight, and
practice stress are predictors of nursing students' clinical competence.
PMID- 26428349
TI - Evaluation of World Health Organization Multi-Professional Patient Safety
Curriculum Topics in Nursing Education: Pre-test, post-test, none-experimental
study.
AB - The Multi-professional Patient Safety Curriculum Guide was launched by the World
Health Organization to develop a patient safety-friendly curriculum in health
education. The aim of this study was to evaluate the impact of teaching related
to two topics from the Patient Safety Curriculum Guide on student nurses'
knowledge and attitudes toward patient safety. A pretest, posttest,
nonexperimental design was used. Patient safety education questionnaires were
distributed to a convenience sample of 181 nursing students before the
intervention, and 141 questionnaires after the intervention in one university in
the East of England. The intervention consisted of two face-to-face lectures and
one facilitated group work discussion. Seventy-one responses from pre- and
posttest stages were matched. Paired t test, McNemar's test, and frequency
measures were used for data analysis. The findings suggest that there are
statistically significant differences in the subscales of the error and patient
safety and personal influence over safety. The differences in the students'
answers on patient safety knowledge before and after the interventions were not
statistically significant. Although the student nurses highly commended the
teaching delivered in this study, the use of experimental design in future
curriculum evaluation may provide a more complementary insight to the findings of
this study.
PMID- 26428350
TI - The Stressors and Coping Strategies of Older Adults With Persistent Atrial
Fibrillation Prior to and Following Direct Current Cardioversion.
AB - OBJECTIVE: The purpose of this study was to explore the stressors and coping
strategies of older adults with persistent atrial fibrillation (AF) before and
after direct current cardioversion. METHOD: The study used a qualitative
descriptive design. Sixteen patients were recruited through an AF clinic to
participate in individual interviews prior to the cardioversion and at 6 and 12
weeks post procedure. RESULTS: Pre-cardioversion, older adults experienced
symptom and health care-related stressors superimposed on existing non-AF
stressors. They used a range of emotion and problem-focused coping. Non-AF
stressors increased post procedure at the same time that participants perceived
less need for coping strategies with a return to regular rhythm. DISCUSSION:
There was a shift from AF to non-AF related stressors following the cardioversion
but a decrease in coping strategies. Older adults with AF should be encouraged to
maintain use of coping strategies to manage ongoing stress and reduce the risk of
AF recurrence.
PMID- 26428351
TI - Transcranial Magnetic Stimulation for Bipolar Disorder with Catatonic Stupor: A
Case Report.
PMID- 26428353
TI - Nutritional Impact of a Gluten-Free Casein-Free Diet in Children with Autism
Spectrum Disorder.
AB - We compared anthropometric values, nutrient intake, the Healthy Eating Index and
food variety in children with autism spectrum disorder (ASD), 20 on a gluten-free
casein-free (GFCF) diet and 85 on a regular diet in Valencia (Spain) using 3-days
food diaries. Those on the GFCF diet had a lower weight, body mass index, and
total energy, pantothenic acid, calcium, phosphorus and sodium intake, but a
higher intake of fiber, legumes, and vegetables. Further, the GFCF diet group had
a better quality of fat intake, but needed supplementation with vitamin D.
Randomized controlled trials are required to explore long-term effects of this
diet on anthropometric and nutritional status (the focus of our study), but also
behavioral symptoms, in children with ASD.
PMID- 26428352
TI - Brexpiprazole Alters Monoaminergic Systems following Repeated Administration: an
in Vivo Electrophysiological Study.
AB - BACKGROUND: Brexpiprazole was recently approved as adjunctive therapy for
depression and treatment of schizophrenia in adults. To complement results from a
previous study in which its acute effects were characterized, the present study
assessed the effect of repeated brexpiprazole administration on monoaminergic
systems. METHODS: Brexpiprazole (1mg/kg, subcutaneous) or vehicle was
administered once daily for 2 and 14 days. Single-unit electrophysiological
recordings from noradrenaline neurons in the locus coeruleus, serotonin neurons
in the dorsal raphe nucleus, dopaminergic neurons in the ventral tegmental area,
and pyramidal neurons in the hippocampus CA3 region were obtained in adult male
Sprague-Dawley rats under chloral hydrate anesthesia within 4 hours after final
dosing. RESULTS: Brexpiprazole blunted D2 autoreceptor responsiveness, while
firing activity of ventral tegmental area dopaminergic neurons remained
unaltered. Brexpiprazole increased the firing rate of locus coeruleus
noradrenaline neurons and increased noradrenaline tone on alpha2-adrenergic
receptors in the hippocampus. Administration of brexpiprazole for 2 but not 14
days increased the firing rate of serotonin neurons in the dorsal raphe nucleus.
In the hippocampus, serotonin1A receptor blockade significantly disinhibited
pyramidal neurons after 2- and 14-day brexpiprazole administration. In contrast,
no significant disinhibition occurred after 24-hour washout or acute
brexpiprazole. CONCLUSIONS: Repeated brexpiprazole administration resulted in a
marked occupancy of D2 autoreceptors, while discharge activity of ventral
tegmental area dopaminergic neurons remained unaltered. Brexpiprazole enhanced
serotonergic and noradrenergic tone in the hippocampus, effects common to
antidepressant agents. Together, these results provide further insight in the
neural mechanisms by which brexpiprazole exerts antidepressant and antipsychotic
effects.
PMID- 26428354
TI - Long-Term Outcomes in Children Diagnosed with Autism Spectrum Disorders in India.
AB - We investigated long-term outcomes in children with diagnosis of autism spectrum
disorders based on Childhood Autism Rating Scale (CARS score). Information about
outcomes such as speech, friendships and activities of daily living (ADLs) was
collected through telephone-based interviews. Gilliam Autism Rating Scale-2 and
Vineland Social Maturity Scale were used to assess level of functioning at follow
up. Parents of 80 [67 males, mean age 12 (3) years] children participated in the
interview, 23 attended follow-up assessment. Sixty-four (80%) were verbal, 34
(42.5%) had need-based speech, 20 (25%) had friends and 37 (46%) had achieved age
appropriate ADLs. Median total follow-up period was 10 years. Lower disease
severity, parent participation and higher maternal education were associated with
better outcomes.
PMID- 26428355
TI - 4-PBA prevents pressure overload-induced myocardial hypertrophy and interstitial
fibrosis by attenuating endoplasmic reticulum stress.
AB - Our previous study indicated that attenuation of endoplasmic reticulum (ER)
stress by administration of 4-phenylbutyric acid (4-PBA) could prevent cardiac
rupture and remodeling in a mouse model of myocardial infarction (MI). However,
whether 4-PBA is protective in hypertrophic heart disease is unclear. Thus, we
tested the therapeutic effect of 4-PBA on pressure-overload induced myocardial
hypertrophy. Transverse aortic constriction (TAC) was used to create myocardial
hypertrophy in C57BL/6 male mice for 4 weeks. Immediately after surgery, the mice
were administrated either 4-PBA (20 mg/kg/day) or 0.9% NaCl by intraperitoneal
injection. At the end of 4 weeks, the mice underwent high-resolution
echocardiographic imaging. Our results showed that both the left ventricular
posterior wall thickness at end systole (LVPWs) and diastole (LVPWd) were
increased in the TAC group, compared to control. 4-PBA administration attenuated
hypertrophy and decreased the heart weight over body weight ratio. Masson's
trichrome staining showed that myocardial interstitial fibrosis and collagen
deposition were also decreased by 4-PBA. We next detected the ER stress response
in the heart tissues of TAC mice in different time points. Western blotting
showed that the expression of ER stress marker, GRP78, CHOP and phosphor-PERK,
were persistently increased 4 weeks after TAC. The treatment of 4-PBA inhibited
the expression of ER stress markers. We also demonstrated that the 4-PBA at 20
mg/kg/day had no effect on histone 3 deacetylation inhibition, while attenuating
ER stress and TAC-induced hypertrophy. These findings suggest that 4-PBA may be a
therapeutic strategy to consider in preventing pressure-overload induced
myocardial hypertrophy and interstitial fibrosis by selectively attenuating ER
stress.
PMID- 26428356
TI - Chemical characteristics for optimizing CYP2E1 inhibition.
AB - Cytochrome P450 2E1 (CYP2E1) expression and activity in the liver is associated
with the degree of liver damage in patients with alcoholic steatohepatitis (ASH)
as well as non-alcoholic steatohepatitis (NASH). CYP2E1 is known to generate
reactive oxygen species, which leads to oxidative stress, one of the hallmarks of
both diseases. Apart from ROS, toxic metabolites can be formed by CYP2E1
metabolism, further potentiating liver injury. Therefore, CYP2E1 is implicated in
the pathogenesis of ASH and NASH. The aim of this study was to determine the
chemical characteristics of compounds that are important to inhibit CYP2E1. To
this end, structurally related analogs that differed in their lipophilic, steric
and electronic properties were tested. In addition, homologues series of
aliphatic primary alcohols, secondary alcohols, aldehydes, ketones and carboxylic
acids were tested. It was found that inhibition of the CYP2E1 activity is
primarily governed by lipophilicity. The optimal log D7.4 (octanol/water
distribution coefficient at pH 7.4) value for inhibition of CYP2E1 was
approximately 2.4. In the carboxylic acids series the interaction of the
carboxylate group with polar residues lining the CYP2E1 active site also has to
be considered. This study sketches the basic prerequisites in the search for
inhibitors of CYP2E1, which would strengthen our therapeutic armamentarium
against CYP2E1 associated diseases, such as ASH and NASH.
PMID- 26428357
TI - Pharmacokinetics of Glycopyrronium Following Repeated Once-Daily Inhalation in
Healthy Chinese Subjects.
AB - BACKGROUND AND OBJECTIVES: Glycopyrronium is a once-daily long-acting muscarinic
antagonist for the maintenance treatment of patients with chronic obstructive
pulmonary disease. This study assessed the pharmacokinetics of inhaled
glycopyrronium 50 ug once-daily for 14 days in healthy Chinese subjects. METHODS:
In this open-label study, 12 Chinese healthy subjects (six males and six females;
mean age 23.1 years [range 18-26 years]) were enrolled and completed the study.
Glycopyrronium in plasma was determined using validated liquid chromatography
mass spectrometry method with a lower limit of quantification of 1.5 pg/mL.
Plasma pharmacokinetic parameters were determined on Day 1 after first dose and
on Day 14 (steady state) after last dose using non-compartmental analysis. Trough
pharmacokinetic samples (Days 5, 7, 10 and 12) were collected. Safety was also
assessed. RESULTS: Glycopyrronium was rapidly absorbed into the systemic
circulation after inhalation and its plasma concentrations decreased rapidly
thereafter. Median time to reach maximum concentration (T max) was reached within
5 min after inhalation on both Days 1 and 14. Accumulation in the systemic
exposure to glycopyrronium was observed from the time of first dose
administration on Day 1 up to Day 14 and the observed accumulation ratio (R acc)
values of area under the plasma drug concentration-time curve [AUC] from time 0
to 24 h post-dose (AUC0-24h) and maximum plasma drug concentration (C max) (Day
14/Day 1) were 2.77 and 1.59, respectively. The elimination half-life (T 1/2) was
not reported. Mean effective half-life (T 1/2,acc) was 37.7 h. Pharmacokinetic
steady state was reached after 5 days of daily dosing. One subject experienced
dry mouth; otherwise glycopyrronium was well tolerated. CONCLUSIONS: Comparison
of systemic exposure to glycopyrronium in Chinese versus the non-Chinese
population did not indicate clinically relevant ethnic differences. Multiple
inhaled doses of glycopyrronium were safe and well tolerated.
PMID- 26428358
TI - Convection-enhanced delivery of an anti-miR is well-tolerated, preserves anti-miR
stability and causes efficient target de-repression: a proof of concept.
AB - Over-expressed microRNAs (miRs) are promising new targets in glioblastoma (GBM)
therapy. Inhibition of over-expressed miRs has been shown to diminish GBM
proliferation, invasion and angiogenesis, indicating a significant therapeutic
potential. However, the methods utilized for miR inhibition have had low
translational potential. In clinical trials convection-enhanced delivery (CED)
has been applied for local delivery of compounds in the brain. The aim of this
study was to determine if safe and efficient miR inhibition was possible by CED
of an anti-miR. We used a highly invasive GBM orthotopic xenograft model and
targeted a well-validated miR, let-7a, with a 2'-O-methoxyethyl anti-miR with a
combined phosphodiester/phosphorothioate backbone to establish an initial proof
of concept. In vitro, anti-let-7a was delivered unassisted to the patient-derived
T87 glioblastoma spheroid culture. In vivo, anti-let-7a or saline were
administered by CED into orthotopic T87-derived tumors. After 1 month of
infusion, tumors were removed and tumor mRNA levels of the target-gene High
mobility group AT-hook 2 (HMGA2) were determined. In vitro, 5 days inhibition was
superior to 1 day at de-repressing the let-7a target HMGA2 and the inhibition was
stable for 24 h. In vivo, anti-miR integrity was preserved in the pumps and no
animals showed signs of severe adverse effects attributable to the anti-miR
treatment. HMGA2 tumor level was significantly de-repressed in the anti-miR
treated animals. The results showed-as an initial proof of concept-that miRs can
be efficiently inhibited using CED delivery of anti-miR. The next step is to
apply CED for anti-miR delivery focusing on key oncogenic miRs.
PMID- 26428359
TI - Adapting Screening, Brief Intervention, and Referral to Treatment for Alcohol and
Drugs to Culturally Diverse Clinical Populations.
AB - OBJECTIVES: To review the literature on the screening, brief intervention, and
referral to treatment (SBIRT) approach to alcohol and drug use with racial and
ethnic subgroups in the United States and to develop recommendations for
culturally competent SBIRT practice. METHODS: Articles reporting on the use of
SBIRT components (screening, brief intervention, referral to treatment) for
alcohol and drug use were identified through a comprehensive literature search of
PubMed from 1995 to 2015. RESULTS: A synthesis of the published literature on
racial and ethnic considerations regarding SBIRT components (including
motivational interviewing techniques) was created using evidence-based findings.
Recommendations on culturally competent use of SBIRT with specific ethnic groups
are also described. CONCLUSIONS: On the basis of the literature reviewed, SBIRT
offers a useful set of tools to help reduce risky or problematic substance use.
Special attention to validated screeners, appropriate use of language/literacy,
trust building, and incorporation of patient and community health care
preferences may enhance SBIRT acceptability and effectiveness. PRACTICE
IMPLICATIONS: Providers should consider the implications of previous research
when adapting SBIRT for diverse populations, and use validated screening and
brief intervention methods. The accompanying case illustration provides
additional information relevant to clinical practice.
PMID- 26428360
TI - Cultural Adaptation of Screening, Brief Intervention and Referral to Treatment
Using Motivational Interviewing.
AB - This clinical case presentation and discussion illustrates a culturally adapted
alcohol and drug use intervention using the Screening, Brief Intervention, and
Referral to Treatment (SBIRT) approach, incorporating motivational interviewing
skills. This case conference serves to complement the accompanying review article
on SBIRT with diverse cultural groups, placing information from the review in the
context of a typical clinical setting. In this example, SBIRT is provided in a
primary care clinic to a Latino patient who reports hazardous drinking,
depression, chronic pain and use of prescription opioids.
PMID- 26428363
TI - Interstitial cells of Cajal increased in patients with rectal prolapse.
PMID- 26428361
TI - Correlates of Opioid Use in Adults With Self-Reported Drug Use Recruited From
Public Safety-Net Primary Care Clinics.
AB - OBJECTIVES: The purpose of this study was to compare demographic, clinical, and
survival characteristics of drug-using safety-net primary care patients who used
or did not use opioids, and to examine treatment implications of our findings.
METHODS: The sample consisted of 868 adults who reported illicit drug use in the
90 days before study enrollment, 396 (45.6%) of whom were opioid users. RESULTS:
Multiple measures indicated that, as a group, opioid users were less physically
and psychiatrically healthy than drug users who did not endorse using opioids,
and were heavy users of medical services (eg, emergency departments, inpatient
hospitals, and outpatient medical) at considerable public expense. After
adjusting for age, they were 2.61 (confidence interval, 1.48-4.61) times more
likely to die in the 1 to 5 years after study enrollment and more likely to die
from accidental poisoning than nonopioid users. Subgroup analyses suggested
patients using any nonprescribed opioids had more serious drug problems including
more intravenous drug use and greater HIV risk than patients using opioids only
as prescribed. CONCLUSIONS: Use of opioids adds a dimension of severity over and
above illicit drug use as it presents in the primary care setting. Opioid users
may benefit from psychiatric and addiction care integrated into their primary
care setting, naloxone overdose prevention kits, and prevention efforts such as
clean needle exchanges. Addiction or primary care providers are in a key position
to facilitate change among such patients, especially the third or more opioid
users having a goal of abstinence from drugs.
PMID- 26428364
TI - Practical problems of measuring depth of submucosal invasion in T1 colorectal
carcinomas.
AB - PURPOSE: Submucosal invasion depth (SID) in colorectal carcinoma (CRC) is an
important factor in estimating risk of lymph node metastasis, but can be
difficult to measure, leading to inadequate or over-extensive treatment. Here, we
aimed to clarify the practical aspects of measuring SID in T1 CRC. METHODS: We
investigated 568 T1 CRCs that were resected surgically at our hospital from April
2001 to December 2013, and relationships between SID and clinicopathological
factors, including the means of measurement, lesion morphology, and lymph node
metastasis. RESULTS: Of these 568 lesions, the SID was >=1000 MUm in 508 lesions.
SIDs for lesions measured from the surface layer were all >=1000 MUm. Although
lesions with SIDs >=1000 MUm were associated with significantly higher levels of
unfavorable histologic types and lymphovascular infiltration than shallower
lesions, a depth of >=1000 MUm was not a significant risk factor for lymph node
metastasis (LNM) (6.7 vs. 9.8 %; P = 0.64), and no lesions for which the sole
pathological factor was SID >=1000 MUm had lymph node metastasis. Protruded
lesions showed deeper SIDs than other types. CONCLUSIONS: Although we found
several problems of measuring SID in this study, we also found, surprisingly,
that SID is not a risk factor for lymph node metastasis, and its measurement is
not needed to estimate the risk of lymph node metastasis.
PMID- 26428365
TI - Proximal humeral osteoarticular allografts: technique, pearls and pitfalls,
outcomes.
AB - Allograft transplantation is a biologic reconstruction option for massive bone
defects after resection of bone sarcomas. This type of reconstruction not only
restores bone stock but it also allows us to reconstruct the joint anatomically.
These factors are a major concern, especially in a young and active population.We
are describing indications, surgical techniques, pearls and pitfalls, and
outcomes of proximal humeral osteoarticular allografts, done at present time in
our institution.We found that allograft fractures and articular complications, as
epiphyseal resorption and subchondral fracture, are the main complications
observed in proximal humerus osteoarticular allograft reconstructions.
Nevertheless, only fractures need a reconstruction revision. Joint complications
may adversely affect the limb function, but for this reason, an allograft
revision is rarely performed.
PMID- 26428366
TI - Response to: Practice of first aid in burn related injuries in a developing
country.
AB - Traditional remedies for burns first aid are rarely compliant with current best
practice. Greater Manchester is one of the most ethnically diverse regions in the
UK. Our burns centre has noted the prevalent use of traditional remedies over
recognised first aid prior to presentation. We review traditional burns remedies
and highlight the importance of burns first aid education that is accessible to
migrant communities.
PMID- 26428367
TI - Antitumor activity of ginseng sapogenins, 25-OH-PPD and 25-OCH3-PPD, on gastric
cancer cells.
AB - OBJECTIVES: 25-Hydroxyprotopanaxadiol (25-OH-PPD) and 25-methoxylprotopanaxadiol
(25-OCH3-PPD), two ginseng sapogenins, have potent antitumor activity and their
effects on gastric cancer (BGC-823, SGC-7901, MKN-28) cells and a gastric mucosa
(GES-1) cell line are reported. RESULTS: Both compounds significantly inhibited
the growth of gastric cancer cells, while having lesser inhibitory effects on GES
1 cells by MTT assay. A mechanistic study revealed that the two ginseng
sapogenins could induce apoptosis in BGC-823 cells by morphological observation,
DNA fragmentation, flow cytometry and western blot analysis. Besides, the
apoptosis was inhibited by Ac-DEVD-CHO, a caspase 3 inhibitor, which was
confirmed by cell viability analysis. CONCLUSIONS: These results indicate that 25
OH-PPD and 25-OCH3-PPD have potential to be promising agents for the treatment of
gastric cancer.
PMID- 26428368
TI - Increased production of plumbagin in Plumbago indica root cultures by biotic and
abiotic elicitors.
AB - OBJECTIVES: To evaluate the effects of 12 biotic and abiotic elicitors for
increasing the production of plumbagin in Plumbago indica root cultures. RESULTS:
Most elicitors showed minimal effects on the root dry weight, except for 250 mg
chitosan l(-1) and 10 mM L-alanine that markedly decreased root biomass by about
40 % compared to the untreated root cultures (5 g l(-1)). Treatments with 100 uM
AgNO3 significantly increased intracellular plumbagin production by up to 7.6 mg
g(-1) DW that was 4-fold more than the untreated root cultures (1.9 mg g(-1) DW).
In contrast, treatments with 150 mg chitosan l(-1), 5 mM L-alanine, and 50 uM 1
naphthol significantly enhanced the extracellular secretion of plumbagin by up to
10.6, 6.9, and 5.7 mg g(-1) DW, respectively, and increased the overall
production of plumbagin by up to 12.5, 12.5, and 9.4 mg g(-1) DW, respectively.
CONCLUSIONS: Chitosan (150 mg l(-1)), L-alanine (5 mM), and 1-naphthol (50 uM)
were the best elicitors to enhance plumbagin production in P. indica root
cultures.
PMID- 26428369
TI - Lung injury caused by greenstick fracture of the scapular body in a 6-year-old
boy.
AB - Complications caused by a scapular body fracture are rare, and usually occur due
to concomitant injuries or nonunion. Intrathoracic displacement of a fractured
scapula has only been described in two reports involving adolescents. In this
report, we describe a 6-year-old boy with a parenchymal lung injury caused by a
greenstick fracture fragment of the scapular body after being struck by a dump
truck. Three-dimensional CT (3D CT) scan showed an incomplete fractured fragment
impaling the left lung parenchyma resulting in pneumothorax, parenchymal
contusion, and pneumatocele in the left upper lobe. The patient underwent
emergency open reduction of the scapular fracture and chest tube insertion. A
rare subtype of scapular fracture with resultant fragment rotation and
intrathoracic penetration can injure the lung parenchyma. To the best of our
knowledge, lung injury caused by incomplete fracture of the scapula in patients
younger than 10 years has not been reported previously.
PMID- 26428370
TI - EBNA1.
AB - Epstein-Barr nuclear antigen 1 (EBNA1) plays multiple important roles in EBV
latent infection and has also been shown to impact EBV lytic infection. EBNA1 is
required for the stable persistence of the EBV genomes in latent infection and
activates the expression of other EBV latency genes through interactions with
specific DNA sequences in the viral episomes. EBNA1 also interacts with several
cellular proteins to modulate the activities of multiple cellular pathways
important for viral persistence and cell survival. These cellular effects are
also implicated in oncogenesis, suggesting a direct role of EBNA1 in the
development of EBV-associated tumors.
PMID- 26428371
TI - EBNA2 and Its Coactivator EBNA-LP.
AB - While all herpesviruses can switch between lytic and latent life cycle, which are
both driven by specific transcription programs, a unique feature of latent EBV
infection is the expression of several distinct and well-defined viral latent
transcription programs called latency I, II, and III. Growth transformation of B
cells by EBV in vitro is based on the concerted action of Epstein-Barr virus
nuclear antigens (EBNAs) and latent membrane proteins(LMPs). EBV growth
transformed B-cells express a viral transcriptional program, termed latency III,
which is characterized by the coexpression of EBNA2 and EBNA-LP with EBNA1,
EBNA3A, -3B, and -3C as well as LMP1, LMP2A, and LMP2B. The focus of this review
will be to discuss the current understanding of how two of these proteins, EBNA2
and EBNA-LP, contribute to EBV-mediated B-cell growth transformation.
PMID- 26428372
TI - The EBNA3 Family: Two Oncoproteins and a Tumour Suppressor that Are Central to
the Biology of EBV in B Cells.
AB - Epstein-Barr virus nuclear antigens EBNA3A , EBNA3B and EBNA3C are a family of
three large latency-associated proteins expressed in B cells induced to
proliferate by the virus. Together with the other nuclear antigens (EBNA-LP,
EBNA2 and EBNA1), they are expressed from a polycistronic transcription unit that
is probably unique to B cells. However, compared with the other EBNAs, hitherto
the EBNA3 proteins were relatively neglected and their roles in EBV biology
rather poorly understood. In recent years, powerful new technologies have been
used to show that these proteins are central to the latency of EBV in B cells,
playing major roles in reprogramming the expression of host genes affecting cell
proliferation, survival, differentiation and immune surveillance. This indicates
that the EBNA3s are critical in EBV persistence in the B cell system and in
modulating B cell lymphomagenesis. EBNA3A and EBNA3C are necessary for the
efficient proliferation of EBV-infected B cells because they target important
tumour suppressor pathways--so operationally they are considered oncoproteins. In
contrast, it is emerging that EBNA3B restrains the oncogenic capacity of EBV, so
it can be considered a tumour suppressor--to our knowledge the first to be
described in a tumour virus. Here, we provide a general overview of the EBNA3
genes and proteins. In particular, we describe recent research that has
highlighted the complexity of their functional interactions with each other, with
specific sites on the human genome and with the molecular machinery that controls
transcription and epigenetic states of diverse host genes.
PMID- 26428373
TI - The Latent Membrane Protein 1 (LMP1).
AB - Almost exactly twenty years after the discovery of Epstein-Barr virus (EBV), the
latent membrane protein 1 (LMP1) entered the EBV stage, and soon thereafter, it
was recognized as the primary transforming gene product of the virus. LMP1 is
expressed in most EBV-associated lymphoproliferative diseases and malignancies,
and it critically contributes to pathogenesis and disease phenotypes. Thirty
years of LMP1 research revealed its high potential as a deregulator of cellular
signal transduction pathways leading to target cell proliferation and the
simultaneous subversion of cell death programs. However, LMP1 has multiple roles
beyond cell transformation and immortalization, ranging from cytokine and
chemokine induction, immune modulation, the global alteration of gene and
microRNA expression patterns to the regulation of tumor angiogenesis, cell-cell
contact, cell migration, and invasive growth of tumor cells. By acting like a
constitutively active receptor, LMP1 recruits cellular signaling molecules
associated with tumor necrosis factor receptors such as tumor necrosis factor
receptor-associated factor (TRAF) proteins and TRADD to mimic signals of the
costimulatory CD40 receptor in the EBV-infected B lymphocyte. LMP1 activates NF
kappaB, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase
(PI3-K), IRF7, and STAT pathways. Here, we review LMP1's molecular and biological
functions, highlighting the interface between LMP1 and the cellular signal
transduction network as an important factor of virus-host interaction and a
potential therapeutic target.
PMID- 26428374
TI - Latent Membrane Protein 2 (LMP2).
AB - LMP2A is an EBV-encoded protein with three domains: (a) an N-terminal cytoplasmic
domain, which has PY motifs that bind to WW domain-containing E3 ubiquitin
ligases and an ITAM that binds to SH2 domain-containing proteins, (b) a
transmembrane domain with 12 transmembrane segments that localizes LMP2A in
cellular membranes, and (c) a 27-amino acid C-terminal domain which mediates
homodimerization and heterodimerization of LMP2 protein isoforms. The most
prominent two isoforms of the protein are LMP2A and LMP2B. The LMP2B isoform
lacks the 19-amino acid N-terminal domain found in LMP2A, which modulates
cellular signaling resulting in a baseline activation of B cells and degradation
of cellular kinases leading to the downregulation of normal B cell signaling
pathways. These two seemingly contradictory processes allow EBV to establish and
maintain latency. LMP2 is expressed in many EBV-associated malignancies. While
its antigenic properties may be useful in developing LMP2-specific immunity, the
LMP2A N-terminal motifs also provide a basis to target LMP2A-modulated cellular
kinases for the development of treatment strategies.
PMID- 26428376
TI - Viral Entry.
AB - Epstein-Barr virus primarily, though not exclusively, infects B cells and
epithelial cells. Many of the virus and cell proteins that are involved in entry
into these two cell types in vitro have been identified, and their roles in
attachment and fusion are being explored. This chapter discusses what is known
about entry at the cellular level in vitro and describes what little is known
about the process in vivo. It highlights some of the questions that still need to
be addressed and considers some models that need further testing.
PMID- 26428377
TI - Epstein-Barr Virus Lytic Cycle Reactivation.
AB - Epstein-Barr virus, which mainly infects B cells and epithelial cells, has two
modes of infection: latent and lytic. Epstein-Barr virus infection is
predominantly latent; however, lytic infection is detected in healthy
seropositive individuals and becomes more prominent in certain pathological
conditions. Lytic infection is divided into several stages: early gene
expression, DNA replication, late gene expression, assembly, and egress. This
chapter summarizes the most recent progress made toward understanding the
molecular mechanisms that regulate the different lytic stages leading to
production of viral progeny. In addition, the chapter highlights the potential
role of lytic infection in disease development and current attempts to purposely
induce lytic infection as a therapeutic approach.
PMID- 26428378
TI - Innate Immune Recognition of EBV.
AB - The ability of Epstein-Barr virus (EBV) to establish latency despite specific
immune responses and to successfully persist lifelong in the human host shows
that EBV has developed powerful strategies and mechanisms to exploit, evade,
abolish, or downsize otherwise effective immune responses to ensure its own
survival. This chapter focuses on current knowledge on innate immune responses
against EBV and its evasion strategies for own benefit and summarizes the
questions that remain to be tackled. Innate immune reactions against EBV
originate both from the main target cells of EBV and from nontarget cells, which
are elements of the innate immune system. Thus, we structured our review
accordingly but with a particular focus on the innate recognition of EBV in its
two stages in its life cycle, latent state and lytic replication. Specifically,
we discuss (I) innate sensing and resulting innate immune responses against EBV
by its main target cells, focusing on (i) EBV transmission between epithelial
cells and B cells and their life cycle stages; and (ii) elements of innate
immunity in EBV's target cells. Further, we debate (II) the innate recognition
and resulting innate immune responses against EBV by cells other than the main
target cells, focusing on (iii) myeloid cells: dendritic cells, monocytes,
macrophages, and neutrophil granulocytes; and (iv) natural killer cells. Finally,
we address (III) how EBV counteracts or exploits innate immunity in its latent
and lytic life cycle stages, concentrating on (v) TLRs; (vi) EBERs; and (vii)
microRNAs.
PMID- 26428375
TI - EBV Noncoding RNAs.
AB - EBV expresses a number of viral noncoding RNAs (ncRNAs) during latent infection,
many of which have known regulatory functions and can post-transcriptionally
regulate viral and/or cellular gene expression. With recent advances in RNA
sequencing technologies, the list of identified EBV ncRNAs continues to grow. EBV
encoded RNAs (EBERs) , the BamHI-A rightward transcripts (BARTs) , a small
nucleolar RNA (snoRNA) , and viral microRNAs (miRNAs) are all expressed during
EBV infection in a variety of cell types and tumors. Recently, additional novel
EBV ncRNAs have been identified. Viral miRNAs, in particular, have been under
extensive investigation since their initial identification over ten years ago.
High-throughput studies to capture miRNA targets have revealed a number of miRNA
regulated viral and cellular transcripts that tie into important biological
networks. Functions for many EBV ncRNAs are still unknown; however, roles for
many EBV miRNAs in latency and in tumorigenesis have begun to emerge. Ongoing
mechanistic studies to elucidate the functions of EBV ncRNAs should unravel
additional roles for ncRNAs in the viral life cycle. In this chapter, we will
discuss our current knowledge of the types of ncRNAs expressed by EBV, their
potential roles in viral latency, and their potential involvement in viral
pathogenesis.
PMID- 26428379
TI - Epstein-Barr Virus-Specific Humoral Immune Responses in Health and Disease.
AB - Epstein-Barr virus (EBV) is widely distributed in the world and associated with a
still increasing number of acute, chronic, malignant and autoimmune disease
syndromes. Humoral immune responses to EBV have been studied for diagnostic,
pathogenic and protective (vaccine) purposes. These studies use a range of
methodologies, from cell-based immunofluorescence testing to antibody-diversity
analysis using immunoblot and epitope analysis using recombinant or synthetic
peptide-scanning. First, the individual EBV antigen complexes (VCA , MA, EA(D),
EA(R) and EBNA) are defined at cellular and molecular levels, providing a
historic overview. The characteristic antibody responses to these complexes in
health and disease are described, and differences are highlighted by clinical
examples. Options for EBV vaccination are briefly addressed. For a selected
number of immunodominant proteins, in particular EBNA1, the interaction with
human antibodies is further detailed at the epitope level, revealing interesting
insights for structure, function and immunological aspects, not considered
previously. Humoral immune responses against EBV-encoded tumour antigens LMP1,
LMP2 and BARF1 are addressed, which provide novel options for targeted
immunotherapy. Finally, some considerations on EBV-linked autoimmune diseases are
given, and mechanisms of antigen mimicry are briefly discussed. Further analysis
of humoral immune responses against EBV in health and disease in carefully
selected patient cohorts will open new options for understanding pathogenesis of
individual EBV-linked diseases and developing targeted diagnostic and therapeutic
approaches.
PMID- 26428380
TI - T-Cell Responses to EBV.
AB - Epstein-Barr virus (EBV) is arguably one of the most successful pathogens of
humans, persistently infecting over ninety percent of the world's population.
Despite this high frequency of carriage, the virus causes apparently few adverse
effects in the vast majority of infected individuals. Nevertheless, the potent
growth transforming ability of EBV means the virus has the potential to cause
malignancies in infected individuals. Indeed, EBV is thought to cause 1% of human
malignancies, equating to 200,000 malignancies each year. A clear factor as to
why virus-induced disease is relatively infrequent in healthy infected
individuals is the presence of a potent immune response to EBV, in particular,
that mediated by T cells. Thus, patient groups with immunodeficiencies or whose
cellular immune response is suppressed have much higher frequencies of EBV
induced disease and, in at least some cases, these diseases can be controlled by
restoration of the T-cell compartment. In this chapter, we will primarily review
the role the alphabeta subset of T cells in the control of EBV in healthy and
diseased individuals.
PMID- 26428381
TI - Immune Evasion by Epstein-Barr Virus.
AB - Epstein-Bar virus (EBV) is widespread within the human population with over 90%
of adults being infected. In response to primary EBV infection, the host mounts
an antiviral immune response comprising both innate and adaptive effector
functions. Although the immune system can control EBV infection to a large
extent, the virus is not cleared. Instead, EBV establishes a latent infection in
B lymphocytes characterized by limited viral gene expression. For the production
of new viral progeny, EBV reactivates from these latently infected cells. During
the productive phase of infection, a repertoire of over 80 EBV gene products is
expressed, presenting a vast number of viral antigens to the primed immune
system. In particular the EBV-specific CD4+ and CD8+ memory T lymphocytes can
respond within hours, potentially destroying the virus-producing cells before
viral replication is completed and viral particles have been released. Preceding
the adaptive immune response, potent innate immune mechanisms provide a first
line of defense during primary and recurrent infections. In spite of this broad
range of antiviral immune effector mechanisms, EBV persists for life and
continues to replicate. Studies performed over the past decades have revealed a
wide array of viral gene products interfering with both innate and adaptive
immunity. These include EBV-encoded proteins as well as small noncoding RNAs with
immune-evasive properties. The current review presents an overview of the evasion
strategies that are employed by EBV to facilitate immune escape during latency
and productive infection. These evasion mechanisms may also compromise the
elimination of EBV-transformed cells, and thus contribute to malignancies
associated with EBV infection.
PMID- 26428382
TI - Non-human Primate Lymphocryptoviruses: Past, Present, and Future.
AB - Epstein-Barr virus (EBV) orthologues from non-human primates (NHPs) have been
studied for nearly as long as EBV itself. Cross-reactive sera and DNA
hybridization studies provided the first glimpses of the closely related
herpesviruses that belonged to the same gamma-1 herpesvirus, or
lymphocryptovirus, genus, as EBV. Over the years, detailed molecular and sequence
analyses of LCVs that infect humans and other NHPs revealed similar colinear
genome structures and homologous viral proteins expressed during latent and lytic
infection. Despite these similarities, experimental infection of NHPs with EBV
did not result in acute symptoms or persistent infection as observed in humans,
suggesting some degree of host species restriction. Genome sequencing and a
molecular clone of an LCV isolate from naturally infected rhesus macaques
combined with domestic colonies of LCV-naive rhesus macaques have opened the door
to a unique experimental animal model that accurately reproduces the normal
transmission, acute viremia, lifelong persistence, and immune responses found in
EBV-infected humans. This chapter will summarize the advances made over the last
50 years in our understanding of LCVs that naturally infect both Old and New
World NHPs, the recent, groundbreaking developments in the use of rhesus macaques
as an animal model for EBV infection, and how NHP LCVs and the rhLCV animal model
can advance future EBV research and the development of an EBV vaccine.
PMID- 26428383
TI - EBV Infection of Mice with Reconstituted Human Immune System Components.
AB - Epstein-Barr virus (EBV) was discovered 50 years ago as the first candidate human
tumor virus. Since then, we have realized that this human gamma-herpesvirus
establishes persistent infection in the majority of adult humans, but fortunately
causes EBV-associated diseases only in few individuals. This is an incredible
success story of the human immune system, which controls EBV infection and its
transforming capacity for decades. A better understanding of this immune control
would not only benefit patients with EBV-associated malignancies, but could also
provide clues how to establish such a potent, mostly cell-mediated immune control
against other pathogens and tumors. However, the functional relevance of EBV
specific immune responses can only be addressed in vivo, and mice with
reconstituted human immune system components (huMice) constitute a small animal
model to interrogate the protective value of immune compartments during EBV
infection, but also might provide a platform to test EBV-specific vaccines. This
chapter will summarize the insights into EBV immunobiology that have already been
gained in these models and provide an outlook into promising future avenues to
develop this in vivo model of EBV infection and human immune responses further.
PMID- 26428385
TI - The Development of Prophylactic and Therapeutic EBV Vaccines.
AB - Over the last century, the development of effective vaccine approaches to treat a
number of viral infections has provided the impetus for the continual development
of vaccine platforms for other viral infections, including Epstein-Barr virus
(EBV). The clinical manifestations associated with EBV infection occur either
following primary infection, such as infectious mononucleosis, or following an
extended period of latency, primarily the EBV-associated malignancies and
potentially including a number of autoimmune disorders, such as multiple
sclerosis. As a consequence, two independent vaccine approaches are under
development to prevent or control EBV-associated diseases. The first approach,
which has been widely successful against other viral infections, is aimed at
inducing a viral neutralisation antibody response to prevent primary infection.
The second approach focuses upon the induction of cell-mediated immunity to
control latent infected cells in persistently infected individuals. Early
clinical studies have offered some insight into the potential efficacy of both of
these approaches.
PMID- 26428386
TI - The Biology and Clinical Utility of EBV Monitoring in Blood.
AB - Epstein-Barr virus (EBV) DNA in blood can be quantified in peripheral blood
mononuclear cells, in circulating cell-free (CCF) DNA specimens, or in whole
blood. CCF viral DNA may be actively released or extruded from viable cells,
packaged in virions or passively shed from cells during apoptosis or necrosis. In
infectious mononucleosis, viral DNA is detected in each of these kinds of
specimens, although it is only transiently detected in CCF specimens. In
nasopharyngeal carcinoma, CCF EBV DNA is an established tumor marker. In EBV
associated Hodgkin lymphoma and in EBV-associated extranodal NK-/T-cell lymphoma,
there is growing evidence for the utility of CCF DNA as a tumor marker.
PMID- 26428384
TI - Adoptive T-Cell Immunotherapy.
AB - Epstein-Barr virus (EBV) is associated with a range of malignancies involving B
cells, T cells, natural killer (NK) cells, epithelial cells, and smooth muscle.
All of these are associated with the latent life cycles of EBV, but the pattern
of latency-associated viral antigens expressed in tumor cells depends on the type
of tumor. EBV-specific T cells (EBVSTs) have been explored as prophylaxis and
therapy for EBV-associated malignancies for more than two decades. EBVSTs have
been most successful as prophylaxis and therapy for post-transplant
lymphoproliferative disease (PTLD) , which expresses the full array of latent EBV
antigens (type 3 latency), in hematopoietic stem-cell transplant (HSCT)
recipients. While less effective, clinical studies have also demonstrated their
therapeutic potential for PTLD post-solid organ transplant and for EBV-associated
malignancies such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, and
nasopharyngeal carcinoma (NPC) that express a limited array of latent EBV
antigens (type 2 latency). Several approaches are actively being pursued to
improve the antitumor activity of EBVSTs including activation and expansion of T
cells specific for the EBV antigens expressed in type 2 latency, genetic
approaches to render EBVSTs resistant to the immunosuppressive tumor environment,
and combination approaches with other immune-modulating modalities. Given the
recent advances and renewed interest in cell therapy, we hope that EBVSTs will
become an integral part of our treatment armamentarium against EBV-positive
malignancies in the near-future.
PMID- 26428387
TI - Female plastic surgery patients prefer mirror-reversed photographs of themselves:
A prospective study.
AB - INTRODUCTION: The use of a patient's image in plastic surgery is common today.
Thus, plastic surgeons should master the use of the image and be aware of the
implications of the patients' perception of themselves. The mere-exposure effect
is a psychological phenomenon in which a person tends to rate things more
positively merely because (s)he is familiar with them. Faces are asymmetric, so
faces in photos are different from those observed in mirrors. The main objective
of this study was to assess whether patients within a plastic surgery population,
particularly those undergoing facial aesthetic surgery, preferred standard
photographs or mirror-reversed photographs of themselves. METHOD: A prospective
study was conducted in a plastic surgery department, which included women who
were admitted to the hospital the day before their procedures. The patients were
separated into the following two groups: Group 1 was composed of patients who
were undergoing facial aesthetic surgeries, and Group 2 consisted of other
patients who presented to the plastic surgery department for surgery. The
patients were required to rate their appreciation of their own faces and to
choose between standard and mirror-reversed photos of themselves. RESULTS: A
total of 214 patients participated. The median age was 47.9 years (interquartile
range (IQR): 36.4-60.6), and the median face appreciation was 5 (IQR: 5-7). The
preference for the mirror-reversed photograph was significantly different from
chance (p < 0.001, binomial (214, 156, 0.5)); 73% of the patients preferred the
mirror-reversed photographs. The proportions of patients who preferred the mirror
reversed photograph differed significantly (p = 0.047) between Groups 1 (84%) and
2 (70%). CONCLUSION: Plastic surgery patients have a significant preference for
mirror-reversed photographs of themselves over standard photographs. This
preference is even more pronounced among patients who are undergoing facial
aesthetic surgery. LEVEL OF EVIDENCE: III.
PMID- 26428388
TI - Hydroxyproline metabolism in a mouse model of Primary Hyperoxaluria Type 3.
AB - Primary Hyperoxaluria Type 3 is a recently discovered form of this autosomal
recessive disease that results from mutations in the gene coding for 4-hydroxy-2
oxoglutarate aldolase (HOGA1). This enzyme is one of the 2 unique enzymes in the
hydroxyproline catabolism pathway. Affected individuals have increased urinary
excretions of oxalate, 4-hydroxy-L-glutamate (4-OH-Glu), 4-hydroxy-2-oxoglutarate
(HOG), and 2,4-dihydroxyglutarate (DHG). While 4-OH-Glu and HOG are precursor
substrates of HOGA1 and increases in their concentrations are expected, how DHG
is formed and how HOG to oxalate are unclear. To resolve these important
questions and to provide insight into possible therapeutic avenues for treating
this disease, an animal model of the disease would be invaluable. We have
developed a mouse model of this disease which has null mutations in the Hoga1
gene and have characterized its phenotype. It shares many characteristics of the
human disease, particularly when challenged by the inclusion of hydroxyproline in
the diet. An increased oxalate excretion is not observed in the KO mice which may
be consistent with the recent recognition that only a small fraction of the
individuals with the genotype for HOGA deficiency develop PH.
PMID- 26428389
TI - Optimization of microwave-assisted extraction conditions for preparing lignan
rich extract from Saraca asoca bark using Box-Behnken design.
AB - CONTEXT: Lyoniside is the major constituent of Saraca asoca Linn.
(Caesalpiniaceae) bark. There is an immediate need to develop an efficient method
to isolate its chemical constituents, since it is a therapeutically important
plant. OBJECTIVE: A rapid extraction method for lyoniside based on microwave
assisted extraction of S. asoca bark was developed and optimized using response
surface methodology (RSM). MATERIALS AND METHODS: Lyoniside was analyzed and
quantified by high-performance liquid chromatography coupled with ultraviolet
detection (HPLC-UV). The extraction solvent ratio (%), material solvent ratio
(g/ml) and extraction time (min) were optimized using Box-Behnken design (BBD) to
obtain the highest extraction efficiency. The optimal conditions were the use of
1:30 material solvent ratio with 70:30 mixture of methanol:water for 10 min
duration. RESULTS: The optimized microwave-assisted extraction yielded 9.4 mg/g
of lyoniside content in comparison to reflux extraction under identical
conditions which yielded 4.2 mg/g of lyoniside content. Under optimum conditions,
the experimental values agreed closely with the predicted values. The analysis of
variance (ANOVA) indicated a high goodness-of-fit model and the success of the
RSM method for optimizing lyoniside extraction from the bark of S. asoca.
DISCUSSION: All the three variables significantly affected the lyoniside content.
Increased polarity of solvent medium enhances the lyoniside yield. CONCLUSION:
The present study shows the applicability of microwave-assisted extraction in
extraction of lyoniside from S. asoca bark.
PMID- 26428390
TI - Structural basis for pore-forming mechanism of staphylococcal alpha-hemolysin.
AB - Staphylococcal alpha-hemolysin (alpha-HL) is a beta-barrel pore-forming toxin
(PFT) expressed by Staphylococcus aureus. alpha-HL is secreted as a water-soluble
monomeric protein, which binds to target membranes and forms membrane-inserted
heptameric pores. To explore the pore-forming mechanism of alpha-HL in detail, we
determined the crystal structure of the alpha-HL monomer and prepore using H35A
mutant and W179A/R200A mutant, respectively. Although the overall structure of
the monomer was similar to that of other staphylococcal PFTs, a marked difference
was observed in the N-terminal amino latch, which bent toward the prestem.
Moreover, the prestem was fastened by the cap domain with a key hydrogen bond
between Asp45 and Tyr118. Prepore structure showed that the transmembrane region
is roughly formed with flexibility, although the upper half of the beta-barrel is
formed appropriately. Structure comparison among monomer, prepore and pore
revealed a series of motions, in which the N-terminal amino latch released upon
oligomerization destroys its own key hydrogen bond between Asp45-Tyr118. This
action initiated the protrusion of the prestem. Y118F mutant and the N-terminal
truncated mutant markedly decreased in the hemolytic activity, indicating the
importance of the key hydrogen bond and the N-terminal amino latch on the pore
formation. Based on these observations, we proposed a dynamic molecular mechanism
of pore formation for alpha-HL.
PMID- 26428391
TI - Antimycoplasmic activity and seasonal variation of essential oil of Eugenia
hiemalis Cambess. (Myrtaceae).
AB - The purpose of this work was to study the chemical composition and
antimycoplasmic and anticholinesterase activities of the essential oil of Eugenia
hiemalis leaves collected throughout the year. A total of 42 compounds were
identified by CG, and are present in almost every seasons. Sesquiterpenes were
dominant (86.01-91.48%), and non-functionalised sesquiterpenes comprised the
major fraction, which increased in the summer; monoterpenes were not identified.
The major components were spathulenol (5.36-16.06%), delta-cadinene (7.50
15.93%), bicyclogermacrene (5.70-14.24%) and beta-caryophyllene (4.80-9.43%). The
highest oil yield was obtained in summer and autumn. Essential oils presented
activity against three evaluated Mycoplasma strains, but no activity was observed
in the anticholinesterase assay.
PMID- 26428392
TI - Therapeutic potential of anti-CD137 (4-1BB) monoclonal antibodies.
AB - INTRODUCTION: 4-1BB (CD137) is an important T-cell stimulating molecule. The 4
1BB mAb or its variants have shown remarkable therapeutic activity against
autoimmunity, viral infections, and cancer. Antibodies to 4-1BB have recently
entered clinical trials for the treatment of cancer with favorable toxicity
profile. In this article, we present a review documenting the efficacy and
pitfalls of 4-1BB therapy. AREAS COVERED: An extensive literature search has been
made on 4-1BB, spanning two decades, and a comprehensive report is presented here
highlighting the origins, biological effects, therapeutic potential, and
mechanistic basis of targeting 4-1BB as well as the side effects associated with
such therapy. EXPERT OPINION: Research so far indicates that 4-1BB is highly
protective against various pathological conditions including cancer. However, a
few important side effects of 4-1BB therapy such as liver toxicity,
thrombocytopenia, anemia, and suppressive effects on certain immune competent
cells should be taken into consideration before it is used for human therapy.
PMID- 26428393
TI - Microfluidic Mobility Shift Profiling of Lysine Acetyltransferases Enables
Screening and Mechanistic Analysis of Cellular Acetylation Inhibitors.
AB - Lysine acetyltransferases (KATs) are critical regulators of signaling in many
diseases, including cancer. A major challenge in establishing the targetable
functions of KATs in disease is a lack of well-characterized, cell-active KAT
inhibitors. To confront this challenge, here we report a microfluidic mobility
shift platform for the discovery and characterization of small molecule KAT
inhibitors. Novel fluorescent peptide substrates were developed for four well
known KAT enzymes (p300, Crebbp, Morf, and Gcn5). Enzyme-catalyzed acetylation
alters the electrophoretic mobility of these peptides in a microfluidic chip,
allowing facile and direct monitoring of KAT activity. A pilot screen was used to
demonstrate the utility of microfluidic mobility shift profiling to identify
known and novel modulators of KAT activity. Real-time kinetic monitoring of KAT
activity revealed that garcinol, a natural product KAT inhibitor used in cellular
studies, exhibits time-dependent and detergent-sensitive inhibition, consistent
with an aggregation-based mechanism. In contrast, the cell-permeable bisubstrate
inhibitor Tat-CoA exhibited potent and time-independent KAT inhibition,
highlighting its potential utility as a cellular inhibitor of KAT activity. These
studies define microfluidic mobility shift profiling as a powerful platform for
the discovery and characterization of small molecule inhibitors of KAT activity,
and provide mechanistic insights potentially important for the application of KAT
inhibitors in cellular contexts.
PMID- 26428395
TI - [Scalp folliculitis: Dissequans or decalvans?].
PMID- 26428396
TI - The impact of having both cancer and diabetes on patient-reported outcomes: a
systematic review and directions for future research.
AB - PURPOSE: This systematic review aims to summarize the current literature
regarding potential effects of having both cancer and diabetes on patient
reported outcomes (PROs) and to provide directions for future research. METHODS:
MEDLINE, The Cochrane Library, CINAHL, and PsycINFO were searched from inception
to January 2015. All English peer-reviewed studies that included patients with
both cancer and diabetes and assessed PROs were included. All included studies
were independently assessed on methodological quality by two investigators.
RESULTS: Of the 3553 identified studies, 10 studies were included and all were
considered of high (40%) or adequate (60%) methodological quality. Eight of the
10 studies focused on health-related quality of life (HRQoL), functioning, or
symptoms and 2 studies assessed diabetes self-management. Overall, HRQoL and
functioning was lower, and symptoms were higher among patients with both cancer
and diabetes as compared to having cancer or diabetes alone. Furthermore, one
study reported that diabetes self-management was impaired after chemotherapy.
CONCLUSIONS: Having both cancer and diabetes resulted in worse PROs compared to
having either one of the diseases, however, the considerable heterogeneity of the
included studies hampered strong conclusions. Future studies are needed as this
research area is largely neglected. As the majority of the included studies
focused on HRQoL, future research should address the impact of both diseases on
other PROs such as depression, patient empowerment and self-management.
IMPLICATIONS FOR CANCER SURVIVOR: Having both cancer and diabetes might result in
worse PROs, however, more research is needed as current evidence is scarce.
PMID- 26428398
TI - Incommensurate modulation and thermal expansion of Sr3B(2 + x)Si(1 - x)O(8 - x/2)
solid solutions.
AB - Crystal structures of Sr3B(2 + x)Si(1 - x)O(8 - x/2) solid solutions with nominal
compositions x = 0.28, 0.53, 0.78 in the Sr3B2SiO8-Sr2B2O5 section of the SrO
B2O3-SiO2 system are refined using single-crystal X-ray diffraction data.
Incommensurate structure modulations are mainly associated with various
orientations of corner-sharing (B,Si)-polyhedra. Preference is given to the (3 +
2)-dimensional symmetry group Pnma(0betagamma)000(0betagamma)000 for a single
crystal compared with an alternate model of a twin formed by monoclinic
components, each of them corresponding to the (3 + 1)-dimensional symmetry group
P2(1)/n(0betagamma). Single-phase polycrystalline samples of solid solutions are
investigated by high-temperature X-ray powder diffraction in air. Orientation
preferences of the BO3 units lead to a strong anisotropy of thermal expansion.
Negative expansion is observed along the a axis over the temperature range 303
753 K. Anisotropy decreases both on heating and decreasing of the boron content.
PMID- 26428399
TI - Two-dimensional zeolite-like network in the new caesium copper aluminate
Cs2CuAl4O8.
AB - Monoclinic dicaesium copper tetraaluminate, Cs2CuAl4O8, space group P2(1)/c, a =
8.4551 (7), b = 10.012 (1), c = 17.073 (2) A, beta = 101.643 (9) degrees , Z = 6,
was obtained by high-temperature crystallization from a phosphate flux. Its
microporous crystal structure presents the first example of double layers built
from [AlO4] tetrahedra combined in 4-, 6- and 8-rings, topologically similar to
those found in the ATT-type zeolites and isostructural minerals armstrongite,
davanite and dalyite. These layers show a rare arrangement of three [AlO4]
tetrahedra sharing one oxygen vertex. The aluminate slabs are further linked by
chains of edge-sharing [CuO4] square planes to form a mixed anionic three
dimensional framework with Cs(+) cations in channels and cavities. An unusually
short Cu...Cs distance of 3.166 A is ascribed to the strong Jahn-Teller effect of
Cu(2+). The magnetic subsystem demonstrates properties of an alternating
antiferromagnetic chain with a gap in the spectrum of magnetic excitations.
PMID- 26428397
TI - Novel JAZ co-operativity and unexpected JA dynamics underpin Arabidopsis defence
responses to Pseudomonas syringae infection.
AB - Pathogens target phytohormone signalling pathways to promote disease. Plants
deploy salicylic acid (SA)-mediated defences against biotrophs. Pathogens
antagonize SA immunity by activating jasmonate signalling, for example
Pseudomonas syringae pv. tomato DC3000 produces coronatine (COR), a jasmonic acid
(JA) mimic. This study found unexpected dynamics between SA, JA and COR and co
operation between JAZ jasmonate repressor proteins during DC3000 infection. We
used a systems-based approach involving targeted hormone profiling, high-temporal
resolution micro-array analysis, reverse genetics and mRNA-seq. Unexpectedly,
foliar JA did not accumulate until late in the infection process and was higher
in leaves challenged with COR-deficient P. syringae or in the more resistant JA
receptor mutant coi1. JAZ regulation was complex and COR alone was insufficient
to sustainably induce JAZs. JAZs contribute to early basal and subsequent
secondary plant defence responses. We showed that JAZ5 and JAZ10 specifically co
operate to restrict COR cytotoxicity and pathogen growth through a complex
transcriptional reprogramming that does not involve the basic helix-loop-helix
transcription factors MYC2 and related MYC3 and MYC4 previously shown to restrict
pathogen growth. mRNA-seq predicts compromised SA signalling in a jaz5/10 mutant
and rapid suppression of JA-related components on bacterial infection.
PMID- 26428400
TI - Classification of ABO3 perovskite solids: a machine learning study.
AB - We explored the use of machine learning methods for classifying whether a
particular ABO3 chemistry forms a perovskite or non-perovskite structured solid.
Starting with three sets of feature pairs (the tolerance and octahedral factors,
the A and B ionic radii relative to the radius of O, and the bond valence
distances between the A and B ions from the O atoms), we used machine learning to
create a hyper-dimensional partial dependency structure plot using all three
feature pairs or any two of them. Doing so increased the accuracy of our
predictions by 2-3 percentage points over using any one pair. We also included
the Mendeleev numbers of the A and B atoms to this set of feature pairs. Doing
this and using the capabilities of our machine learning algorithm, the gradient
tree boosting classifier, enabled us to generate a new type of structure plot
that has the simplicity of one based on using just the Mendeleev numbers, but
with the added advantages of having a higher accuracy and providing a measure of
likelihood of the predicted structure.
PMID- 26428401
TI - Fluorite-related one-dimensional units in natural bismuth oxysulfates: the
crystal structures of Bi14O16(SO4)5 and Bi30O33(SO4)9(AsO4)2.
AB - The crystal structures of two new natural Bi oxysulfates with the formula
Bi14O16(SO4)5 [labelled new phase I; monoclinic, space group C2, a = 21.658 (4),
b = 5.6648 (9), c = 15.092 (3) A, beta = 119.433 (11) degrees and Z = 2] and
Bi30O33(SO4)9(AsO4)2 [labelled new phase II; triclinic, space group P1, a = 5.670
(3), b = 13.9408 (9), c = 22.7908 (18) A, alpha = 80.903 (5), beta = 82.854 (14),
gamma = 78.27 (2) degrees and Z = 1] from the high-temperature fumarole deposit
of the La Fossa crater at Vulcano (Aeolian Islands, Italy) are reported. The
structures are built up by a combination of fluorite-related Bi-O units and
isolated (SO4)(2-) tetrahedra (new phase I) or both (SO4)(2-) and (AsO4)(3-)
tetrahedra (new phase II). Owing to the effect of stereoactive lone pairs of
Bi(3+), Bi-O units in both the structures can be suitably described in terms of
oxo-centered OBi4 tetrahedra. The structure of Bi14O16(SO4)5 is based upon one
dimensional [O16Bi14](10+) ribbons formed by six chains of edge-sharing OBi4
tetrahedra extending along [010]. In the structure of Bi30O33(SO4)9(AsO4)2 the
same ribbon type coexists with another one-dimensional ribbon formed by seven
chains of edge-sharing OBi4 tetrahedra and with the composition [O17Bi16](14+).
Ribbons of the same type are joined by (SO4)(2-) and (AsO4)(3-) tetrahedra along
[010] - if a reduced triclinic unit-cell setting is considered - so forming two
different (001) slabs which alternate to each other along [001] and are joined by
additional (SO4)(2-) tetrahedra. New phase I represents the natural analogues of
synthetic Bi14O16(SO4)5, but with an ordered structure model.
PMID- 26428402
TI - Twinning of three Fe-PNP pincer complexes interpreted according to order-disorder
(OD) theory.
AB - The systematic twinning of three 2,6-diaminopyridine-based Fe-PNP complexes is
interpreted using order-disorder (OD) theory. The monoclinic [Fe(0)(PNP(Et)
(i)Pr)(CO)2] [P112(1)/b, Z' = 4] possesses pseudo-orthorhombic metrics and
crystallizes as a reflection twin by pseudo-merohedry with the twin plane (100).
The structure is made up of layers with idealized p2(1)a(b) symmetry. The a glide
planes of adjacent layers do not overlap, leading to OD polytypism. trans
[Fe(II)(PNP-Et)Br2(CO)] [P2(1)/n, Z' = 1] is systematically twinned via twofold
rotation about [001]. It is made up of OD layers with idealized p2(1)2(1)(2)
symmetry. OD polytypism is caused by the twofold rotation axes of adjacent layers
which do not overlap. [Fe(II)(kappa(2)P,N-PNP-(i)Pr,TAD)Cl2].THF [P1, Z^{?prime}
= 2] is systematically twinned via a twofold rotation about [010]. It is made up
of layers with idealized p121(1) symmetry. OD polytypism is caused by screw
rotations relating adjacent layers with an intrinsic translation along a fourth
of a primitive lattice vector. In all three structures the twin individuals are a
polytype with a maximum degree of order (MDO) and at the twin interface is
located a fragment of the second MDO polytype.
PMID- 26428403
TI - Crystalline state photochromism of 3-furylfulgides: impact of size and bond
flexibility of the non-aromatic alkylidene group.
AB - 3-Furylfulgides are photochromic compounds showing high thermal stability in
their closed forms. However, their photochromic properties in the solid state
should be improved further to fabricate molecular devices. Understanding how the
size and the flexibility of the non-aromatic alkylidene moiety alter the
crystalline state photochromic properties is also important here, as the
alkylidene group is directly involved in the photochromic ring closing and
opening reactions. The synthesis of four 3-furylfulgides composed of different
alkylidene groups (rigid isopropyl, flexible 2-butyl, rigid cyclopentyl and
flexible cyclohexyl), their crystal structures and structure-photochromic
property correlation in the crystalline state are reported here. Crystallographic
data along with reaction cavity volumes calculated using the program CAVITY
[Ohashi et al. (1981), J. Am. Chem. Soc. 103, 5805-5812] disclosed that fulgides
with flexible groups at the ring closing site have more free volume around the
reactive area in the crystal lattice, which can provide more space for the atomic
movements in the reaction and flexibility can reduce the strain built up in the
closed C-isomers by making conformations. According to UV-vis spectroscopic data,
a higher yield of C-isomers and a better fatigue resistance were obtained for the
3-furylfulgide with the largest and flexible cyclohexyl group showing greater
photochromic properties in the crystalline state than the fulgide containing the
smallest and rigid isopropyl group.
PMID- 26428404
TI - Combined analysis of chemical bonding in a Cu(II) dimer using QTAIM, Voronoi
tessellation and Hirshfeld surface approaches.
AB - Interaction of 1-(1H-pyrazol-5-yl)ethanone oxime (H2PzOx) with copper(II)
chloride in the presence of pyridine afforded a binuclear discrete
[Cu2(HPzOx)2Cl2py2] complex, which was characterized by Fourier transform-IR and
electron paramagnetic resonance (EPR) spectra, magnetochemistry and high
resolution X-ray diffraction experiments. Multipole refinement of X-ray
diffraction data and density-functional theory (DFT) calculations of an isolated
molecule allowed charge and spin distributions to be obtained for this compound.
Magnetochemistry data, EPR spectra and DFT calculations of an isolated molecule
show antiferromagnetic coupling between copper(II) ions. The spin distribution
suggests an exchange pathway via the bridging pyrazole ring in the equatorial
plane of the CuN4Cl coordination polyhedron, thus providing support for the
classical superexchange mechanism; the calculated value of the magnetic coupling
constant -2J is equal to 220 cm(-1), which compares well with the experimental
value of 203 +/- 2 cm(-1). Chemical connectivity was derived by Bader's 'quantum
theory of atoms in molecules' and compared with Voronoi tessellation and
Hirshfeld surface representations of crystal space. All methodologies gave a
similar qualitative and semi-quantitative description of intra- and
intermolecular connectivity.
PMID- 26428405
TI - At last! The single-crystal X-ray structure of a naturally occurring sample of
the ilmenite-type oxide FeCrO3.
AB - A natural single crystal of the ferrimagnetic oxide FeCrO3, which was found in an
opencast mine situated in the San Luis Potosi State in Mexico, has been
characterized in order to elucidate some outstanding issues about the actual
structure of this material. The single-crystal X-ray analysis unambiguously shows
that transition metal cations are segregated in alternating layers normal to the
threefold crystallographic axis, affording a structure isomorphous to that of
ilmenite (FeTiO3), in the space group R3. The possible occurrence of cation
antisite and vacancy defects is below the limit of detection available from X-ray
data. Structural and magnetic results are in agreement with the coherent slow
intergrowth of magnetic phases provided by the two antiferromagnetic corundum
type parent oxides Fe2O3 (hematite) and Cr2O3 (eskolaite). Our results are
consistent with the most recent density functional theory (DFT) studies carried
out on digital FeCrO3 [Sadat Nabi & Pentcheva (2011). Phys. Rev. B, 83, 214424],
and suggest that synthetic samples of FeCrO3 might present a cation distribution
different to that of the ilmenite structural type.
PMID- 26428406
TI - Comprehensive derivation of bond-valence parameters for ion pairs involving
oxygen.
AB - Published two-body bond-valence parameters for cation-oxygen bonds have been
evaluated via the root mean-square deviation (RMSD) from the valence-sum rule for
128 cations, using 180,194 filtered bond lengths from 31,489 coordination
polyhedra. Values of the RMSD range from 0.033-2.451 v.u. (1.1-40.9% per unit of
charge) with a weighted mean of 0.174 v.u. (7.34% per unit of charge). The set of
best published parameters has been determined for 128 ions and used as a
benchmark for the determination of new bond-valence parameters in this paper. Two
common methods for the derivation of bond-valence parameters have been evaluated:
(1) fixing B and solving for R(o); (2) the graphical method. On a subset of 90
ions observed in more than one coordination, fixing B at 0.37 A leads to a mean
weighted-RMSD of 0.139 v.u. (6.7% per unit of charge), while graphical derivation
gives 0.161 v.u. (8.0% per unit of charge). The advantages and disadvantages of
these (and other) methods of derivation have been considered, leading to the
conclusion that current methods of derivation of bond-valence parameters are not
satisfactory. A new method of derivation is introduced, the GRG (generalized
reduced gradient) method, which leads to a mean weighted-RMSD of 0.128 v.u. (6.1%
per unit of charge) over the same sample of 90 multiple-coordination ions. The
evaluation of 19 two-parameter equations and 7 three-parameter equations to model
the bond-valence-bond-length relation indicates that: (1) many equations can
adequately describe the relation; (2) a plateau has been reached in the fit for
two-parameter equations; (3) the equation of Brown & Altermatt (1985) is
sufficiently good that use of any of the other equations tested is not warranted.
Improved bond-valence parameters have been derived for 135 ions for the equation
of Brown & Altermatt (1985) in terms of both the cation and anion bond-valence
sums using the GRG method and our complete data set.
PMID- 26428408
TI - In vitro toxicity assay of cisplatin on mouse acute lymphoblastic leukaemia and
spermatogonial stem cells.
AB - Testicular cancer is the most common cancer affecting men in reproductive age,
and cisplatin is one of the major helpful chemotherapeutic agents for treatment
of this cancer. In addition, exposure of testes cancer cells to cisplatin could
potentially eliminate tumour cells from germ cells in patients. The aim of this
study was to evaluate the effect of cisplatin on viability of mouse acute
lymphoblastic leukaemia cell line (EL-4) and neonatal mouse spermatogonial cells
in vitro. In this study, the isolated spermatogonial stem cells (SSC) and EL-4
were divided into six groups including control (received medium), sham (received
DMSO in medium) and experimental groups which received different doses of
cisplatin (0.5, 5, 10 and 15 MUg ml(-1) ). Cells viability was evaluated with MTT
assay. The identity of the cultured cells was confirmed by the expression of
specific markers. Our finding showed that viability of both SSC and EL-4 cells
was reduced with the dose of 15 MUg/ml when compared to the control group (P <=
0.05). Also, the differences between the IC50 in doses 10 and 15 MUg/ml at
different time were significant (P <= 0.05). The number of TUNEL-positive cells
was increased, and the BAX and caspase-3 expressions were upregulated in EL4
cells for group that received an effective dose of cisplatin). In conclusion,
despite the dramatic effects of cisplatin on both cells, spermatogonial stem
cells could form colony in culture.
PMID- 26428409
TI - Efficacy and effects of palifermin for the treatment of oral mucositis in
patients affected by acute lymphoblastic leukemia.
AB - This randomized-controlled trial studied the efficacy of palifermin, administered
as a dose during hematopoietic stem cell transplant (HSCT) therapy, as primary
prophylaxis on pediatric patients with acute lymphoblastic leukemia in order to
reduce oral mucositis (OM). Patients in the palifermin group were randomly
assigned to receive palifermin, 60 MUg/kg, intravenously as a single dose 3 days
before and 0, +1, and +2 post autologous HSCT infusion. The patients in the
control group received only a placebo treatment. OM-related assessments were the
WHO oral-toxicity scale and the patient-reported outcomes. There was a
statistically significant reduction in the incidence of OM grade 3 and 4 in the
palifermin group compared to the control group. There was also a reduction in the
degree of severity of OM in the palifermin group (1.65 grade respect to 2.33 in
the control group). Palifermin could prevent the recurrence of severe OM and
improve the quality of life in patients with acute lymphoblastic leukemia (ALL).
PMID- 26428411
TI - A systematic review of outcome measures used in clinical trials of treatment
interventions following traumatic dental injuries.
AB - BACKGROUND: Traumatic dental injuries (TDI) are common, and appropriate treatment
will maximize the chances of maintaining teeth in function while safeguarding
their longevity and aesthetics. Subjectively, it appears that outcome measures
used in studies investigating TDI are numerous and diverse. OBJECTIVES: To
undertake a systematic review of the outcomes used in clinical trials of
treatment interventions following TDI. DATA SOURCES: The MEDLINE, Cochrane
Central Register of Controlled Trials, Cochrane Database of Systematic Reviews
and EMBASE databases were searched up to June 2014. Reference lists of eligible
studies were cross-checked to identify additional studies and strategies to
identify grey literature and ongoing trials were employed. STUDY SELECTION: Two
authors independently assessed studies for inclusion and undertook data
extraction. The study designs included were as follows: systematic reviews
with/without meta-analyses, randomized and pseudo-randomized controlled trials
and controlled clinical trials. There were no language restrictions. RESULTS: Ten
studies confined to two types of TDI were included: avulsion (5) and non-vital
immature permanent incisor teeth (5). The outcomes reported predominantly
concentrated on injury activity and the physical consequence of injury. There was
little consistency between studies for the length of follow up, the time points
at which outcomes were evaluated or the methods used to measure them.
CONCLUSIONS: There is significant heterogeneity in outcomes reported for TDI in
the literature. These findings preclude meaningful meta-analysis between studies.
Future clinical studies need to consider collecting a more consistent and wider
range of outcomes, which should include one or more from each of the following
domains: health resources utilisation, adverse effects and quality of life and
family outcome. There is a clear need for the development of a Core Outcome Set
for TDI using robust and established methodology, thus optimizing the value of
future research.
PMID- 26428410
TI - Prevalence of Cognitive Impairment and Dementia in Malays - Epidemiology of
Dementia in Singapore Study.
AB - OBJECTIVE: To study the prevalence of cognitive impairment and dementia in
communitydwelling Malays from Singapore; and to examine differences in prevalence
among Chinese and Malays. METHODS: Subjects (>= 60 years) - drawn from the Malay
component of the on-going multiethnic Epidemiology of Dementia in Singapore study
- were screened using locally validated Abbreviated Mental Test and Progressive
Forgetfulness Questionnaire. Subsequently, screen-positive participants underwent
detailed neuropsychological assessments and neuroimaging. Cognitive impairment no
dementia (CIND) and dementia were diagnosed based on accepted criteria. RESULTS:
A total of 966 Malay subjects were included, of whom 102 had CIND-mild, 135
CINDmoderate, and 27 dementia. The overall age-standardized prevalence of any
cognitive impairment was 25.5%, including 2% of dementia. The prevalence of any
cognitive impairment increased with age from 14.9% in those aged 60-64 years to
40.2% in age >=80 years. Women had a higher prevalence of CIND and dementia than
men. Compared to previously published data from EDIS on Chinese, Malay were
nearly twice more likely to have any cognitive impairment (Odds ratios adjusted
for age, demographic and cardiovascular risk factors, and ApoEepsilon4 carrier:
2.03, 95% confidence interval: 1.48-2.77). CONCLUSION: Among elderly Malays, the
overall prevalence of any cognitive impairment was 25.5%. Even with a similar
protocol of recruitment and assessment and adjusting for known risk factors, the
prevalence of cognitive impairment was higher in Malays compared to Chinese.
Further research is needed to unravel other factors that may underlie these
ethnic differences in the occurrence of cognitive impairment.
PMID- 26428412
TI - Sequestration and speciation of Eu(iii) on gamma alumina: role of temperature and
contact order.
AB - The speciation, migration and transport of radionuclides in the environment are
significantly influenced by their interactions with the natural minerals and
humic substances therein. In view of this, the effect of temperature and contact
order on the sorption behaviors of trivalent Eu(iii) in the gamma-Al2O3/Eu(iii)
and gamma-Al2O3/HA/Eu(iii) systems was studied using batch experiments and the
extended X-ray absorption fine structure spectroscopy (EXAFS) technique. The
endothermic sorption behavior of Eu(iii) in the gamma-Al2O3/Eu(iii) systems was
induced by the hydrolysis reaction of Eu(iii) in solution and the complexation of
Eu(iii) with the gamma-Al2O3 surface sites. The endothermic sorption of Eu(iii)
in the gamma-Al2O3/HA/Eu(iii) systems was attributed to the endothermic binding
of HA on gamma-Al2O3 and the endothermic complexation between Eu(iii) and HA.
EXAFS analysis suggested the formation of type B ternary complexes and their
thermodynamic stability improves with rising temperature. The different sorption
percentages under various contact orders were closely related to the binding mode
of Eu(iii) on the exposed gamma-Al2O3 surfaces or the gamma-Al2O3/HA colloids.
The findings obtained herein are important to evaluate the security of the
radioactive waste repository and predict the fate of trivalent actinides (e.g.,
Am(iii), Cm(iii), Pu(iii), etc.) near the geological repository.
PMID- 26428413
TI - Total Synthesis of Codeine.
AB - In this paper, a new strategy towards the synthesis of codeine and morphine is
reported. This new approach features a cascade cyclization to construct the
dihydrofuran ring, and an intramolecular palladium catalyzed C-H olefination of
unactivated aliphatic alkene to install the morphinan ring system.
PMID- 26428414
TI - Liver regeneration after splenectomy in patients with liver cirrhosis.
AB - AIM: Splenectomy is a well-known procedure to improve thrombocytopenia and liver
function in patients with liver cirrhosis (LC). However, the effect of
splenectomy on liver regeneration remains unclear. The aim of this study is to
investigate the effect of splenectomy on liver regeneration. METHODS: Twenty
patients with LC who underwent splenectomy were included in this study. Liver and
splenic volumes were measured by a 3-D simulation imaging system. Liver volume
(LV) and clinicopathological data were compared before and 6 months after
splenectomy. Thereafter, patients were divided into two groups: the elevated LV
group and the reduced LV group. Patient characteristics were compared between the
two groups. RESULTS: Postoperative LV was increased in 14 patients compared with
the preoperative state. Thrombocytopenia, leukopenia, total bilirubin and
prothrombin time were improved after splenectomy. In the elevated LV group, four
patients exhibited improved Child-Pugh grades after splenectomy, whereas no
patients demonstrated improvement in the reduced LV group. The elevated LV group
exhibited high albumin level, good indocyanine green retention rate at 15 min and
large splenic volume compared with the same measurements in the decreased group.
Patients with larger spleen volumes and higher albumin values before splenectomy
showed increased rates of LV after splenectomy. CONCLUSION: Splenectomy for
patients with LC improved pancytopenia and liver function. Especially, in
patients with large spleen and high albumin levels, considerable increases in LV
and improved liver function were observed.
PMID- 26428415
TI - Clean intermittent self-catheterization does not appear to be effective in the
prevention of urethral stricture recurrence.
AB - OBJECTIVE: The aim of this study was to assess the effect of clean intermittent
self-catheterization (CISC) on stricture recurrence. MATERIALS AND METHODS: The
incidence of stricture recurrence was assessed retrospectively in a group of 126
new patients treated endoscopically for urethral stricture in a general
urological setting between 1994 and 2001, of whom 31 performed twice-weekly CISC
and 95 did not. Stricture recurrence was defined as recurrent symptomatic
stricture requiring further operative intervention following initial
intervention. The mean follow-up available was 25 months (range 1-132 months).
RESULTS: Of the 126 patients assessed, 60 (47.6%) developed recurrent stricture
and required an average of 3.13 endoscopic retreatments each during the follow-up
period. There was no significant difference (chi-squared p = 0.46) between the
number of stricture recurrences in those performing CISC (13-41.9%) and those not
performing CISC (47-49.5%). CONCLUSION: CISC does not appear to prevent medium
term stricture recurrence.
PMID- 26428416
TI - The impact of oral anticoagulation on time to surgery in patients hospitalized
with hip fracture.
AB - INTRODUCTION: Current clinical guidelines recommend expedited repair of hip
fracture to reduce morbidity and mortality. A significant number of hip fracture
patients have concomitant cardiovascular disease requiring anticoagulation.
Vitamin K antagonists (VKAs), which have been traditionally used, might be
associated with an increased time to surgery (TTS) and it remains unknown what
effect direct oral anticoagulants (DOACs) have on this metric. Our objective is
to determine how anticoagulation with a VKA or DOAC affects TTS. MATERIALS AND
METHODS: This is a case control study comparing TTS in consecutively admitted hip
fracture patients receiving either a DOAC or VKA with age- and gender-matched
controls between January 1, 2010 and March 24, 2014. The primary end point is
TTS, which is defined as the time elapsed from admission to surgery. Secondary
end points include the rate of stroke, death, bleeding and VTE during admission.
RESULTS: Of 2258 patients, 233 were on a VKA while 27 were on a DOAC. Median TTS
seems to be longer in patients receiving a DOAC or a VKA when compared to
controls. (40 h vs. 26.2h). The DOAC group tended to have longer median TTS when
compared to the VKA groups (66.9h vs. 39.4h) There was no difference in the rate
of stroke, death, bleeding and VTE during admission. CONCLUSIONS: Patients on
anticoagulation prior to admission for hip fracture experienced longer delays in
surgery when compared to patients not receiving anticoagulation. Patients on a
DOAC experienced the longest surgical delay.
PMID- 26428417
TI - Paradigm lost: Reflections on grandparents.
PMID- 26428418
TI - The child with short stature.
PMID- 26428419
TI - ASCIA guidelines for prevention of anaphylaxis in schools, pre-schools and
childcare: 2015 update.
AB - The aim of these guidelines is to assist staff in school and childcare settings
to plan and implement appropriate risk minimisation strategies, taking into
consideration the needs of the allergic child, the likely effectiveness of
measures and the practicality of implementation. Although these guidelines
include risk minimisation strategies for allergic reactions to insect stings or
bites, latex and medication, the major focus relates to food allergy. This is due
to the higher relative prevalence of food allergy in childhood (compared with
other allergic triggers) and the higher likelihood of accidental exposure in
these settings. Care of the allergic child in the school, pre-school or childcare
settings requires accurate information obtained from parents and carers, staff
training in the recognition and management of acute allergic reactions, planning
for unexpected reactions (including in those not previously identified as being
at risk), age appropriate education of children with severe allergies and their
peers, and implementation of practical strategies to reduce the risk of
accidental exposure to known allergic triggers. Strategy development also needs
to take into account local or regional established legislative or procedural
guidelines and the possibility that the first episode of anaphylaxis may occur
outside the home. Food bans are not recommended as the primary risk minimisation
strategy due to difficulties in implementation and lack of proven effectiveness.
PMID- 26428420
TI - Retinopathy of prematurity: New Zealand recommendations for case detection and
treatment.
PMID- 26428421
TI - Is day surgery failing our children?
PMID- 26428422
TI - Psychological interventions for parents of children and adolescents with chronic
illness.
PMID- 26428423
TI - Medecins Sans Frontieres paediatrician profile.
PMID- 26428424
TI - A baby with an oral surprise.
PMID- 26428425
TI - Multicoloured papules on the neck.
PMID- 26428432
TI - Academy of Paediatrics.
PMID- 26428433
TI - Early screening of autism: Is age a confounding factor when screening for autism?
PMID- 26428434
TI - Early screening of autism: Is age a confounding factor when screening for autism?
PMID- 26428435
TI - CXCL14, CXCR7 expression and CXCR4 splice variant ratio associate with survival
and metastases in Ewing sarcoma patients.
AB - PURPOSE: Ewing sarcoma (EWS) is the second most common sarcoma of bone in
children and young adults. Patients with disseminated disease at diagnosis or
early relapse have a poor prognosis. Our goal was to identify novel predictive
biomarkers for these patients, focusing on chemokines, specifically genes
involved in the CXCR4-pathway because of their established role in metastasis and
tumour growth. METHODS: Total RNA isolated from therapy-naive tumour samples
(n=18; panel I) and cell lines (n=21) was used to study expression of CXCR4
pathway related genes and CXCR4 splice variants (CXCR4-2: Small and CXCR4-1:
Large) by RT-Q-PCR. Expression levels were correlated to overall survival (OS)
and event free survival (EFS). Study results were validated in an independent
series of 26 tumour samples (panel II) from therapy-naive tumour samples.
RESULTS: CXCL12, CXCR4, CXCR7 and CXCL14 were expressed and high CXCR7 and CXCL14
expression showed a positive correlation with EFS and OS and a negative
correlation with metastasis development. Both splice variants CXCR4 were
expressed in cell lines and tumour samples and CXCR4-1/CXCR4-2 ratio was
significantly higher in tumour samples compared to cell lines and correlated with
an improved EFS and OS. The results from the test panel were validated in an
independent sample panel. CONCLUSIONS: We identified a set of genes involved in
CXCR4 signalling that may be used as a marker to predict survival and metastasis
development in Ewing sarcoma.
PMID- 26428436
TI - Unmet medical needs for chronic spontaneous urticaria patients: highlighting the
real-life clinical practice in Taiwan.
AB - BACKGROUND: Treatment guidelines for chronic spontaneous/idiopathic urticaria
(CSU) are available; however, only 50% of patients are well controlled with
approved doses of H1-antihistamines, and certain patients remain symptomatic
despite receiving up to 4* the approved dose of H1-antihistamines plus H2
antihistamines and/or leucotriene-receptor antagonists. OBJECTIVES: To highlight
real-life clinical practice in Taiwan and to understand the unmet medical needs
of CSU patients. METHODS: A nationwide cross-sectional, observational survey of
50 dermatologists and 200 CSU patients was conducted between June 2013 and
November 2013. Face-to-face interviews of dermatologists and online interviews of
CSU patients were conducted independently. RESULTS: Dermatologists reported that
dermographism and blood tests were the most commonly used diagnostic methods to
confirm the diagnosis. The key driving factor for most clinic-based
dermatologists (70%) in choosing a treatment was 'response to my medicines', and
most preferred H1-antihistamines and steroids for treating CSU patients, whereas
most hospital-based dermatologists (85%) gave higher priority to 'severity and
impact of the conditions'. Patients were reported to have high psychological
pressures and significant impact of CSU on their daily activity. In addition, CSU
patients were not satisfied with their current treatment and 69% of patients
switched their first-consulted physician. Furthermore, lack of information and
concerns about side-effects were major factors which held back patients from
seeking Western treatment. CONCLUSIONS: There is an unmet medical need of CSU
patients in Taiwan highlighting gaps among guidelines, real-life clinical
practice, patients' perceptions and patients' knowledge of their disease.
PMID- 26428438
TI - Efficient and Accurate Identification of Platinum-Group Minerals by a Combination
of Mineral Liberation and Electron Probe Microanalysis with a New Approach to the
Offline Overlap Correction of Platinum-Group Element Concentrations.
AB - Identification and accurate characterization of platinum-group minerals (PGMs) is
usually a very cumbersome procedure due to their small grain size (typically
below 10 um) and inconspicuous appearance under reflected light. A novel strategy
for finding PGMs and quantifying their composition was developed. It combines a
mineral liberation analyzer (MLA), a point logging system, and electron probe
microanalysis (EPMA). As a first step, the PGMs are identified using the MLA.
Grains identified as PGMs are then marked and coordinates recorded and
transferred to the EPMA. Case studies illustrate that the combination of MLA,
point logging, and EPMA results in the identification of a significantly higher
number of PGM grains than reflected light microscopy. Analysis of PGMs by EPMA
requires considerable effort due to the often significant overlaps between the X
ray spectra of almost all platinum-group and associated elements. X-ray lines
suitable for quantitative analysis need to be carefully selected. As peak
overlaps cannot be avoided completely, an offline overlap correction based on
weight proportions has been developed. Results obtained with the procedure
proposed in this study attain acceptable totals and atomic proportions,
indicating that the applied corrections are appropriate.
PMID- 26428437
TI - A goose-type lysozyme from ostrich (Struthio camelus) egg white: multiple roles
of His101 in its enzymatic reaction.
AB - A goose-type lysozyme from ostrich egg white (OEL) was produced by Escherichia
coli expression system, and the role of His101 of OEL in the enzymatic reaction
was investigated by NMR spectroscopy, thermal unfolding, and theoretical modeling
of the enzymatic hydrolysis of hexa-N-acetylchitohexaose, (GlcNAc)6. Although the
binding of tri-N-acetylchitotriose, (GlcNAc)3, to OEL perturbed several backbone
resonances in the (1)H-(15)N HSQC spectrum, the chemical shift of the backbone
resonance of His101 was not significantly affected. However, apparent pKa values
of His101 and Lys102 determined from the pH titration curves of the backbone
chemical shifts were markedly shifted by (GlcNAc)3 binding. Thermal unfolding
experiments and modeling study of (GlcNAc)6 hydrolysis using a His101-mutated OEL
(H101A-OEL) revealed that the His101 mutation affected not only sugar residue
affinities at subsites -3 and -2 but also the rate constant for bond cleavage.
His101 appears to play multiple roles in the substrate binding and the catalytic
reaction.
PMID- 26428439
TI - Identification of Organic Binders in Ancient Chinese Paintings by Immunological
Techniques.
AB - The identification and localization of organic binders in artworks are big
challenges in archaeology and conservation science. Immunological techniques,
such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence
microscopy (IFM) have the potential to become powerful tools for the analysis of
organic materials in ancient samples. In this study, ELISA and IFM techniques
were combined to identify chicken ovalbumin, glue from several mammalian species,
bovine milk, and fish glue in ancient Chinese painting samples. As binders, egg
ovalbumin was found in two painting samples and animal glue was found in three
samples, which were dated from the 4th to 8th centuries. The results clearly
demonstrate that ELISA and IFM can be used to validate results from ancient
samples.
PMID- 26428440
TI - Interferometric Diffraction from Amorphous Double Films.
AB - We explore the interference fringes that arise in diffraction patterns from
double-layer amorphous samples where there is a substantial separation, up to
about a micron, between two overlapping thin films. This interferometric
diffraction geometry, where both waves have interacted with the specimen, reveals
phase gradients within microdiffraction patterns. The rapid fading of the
observed fringes as the magnitude of the diffraction vector increases confirms
that displacement decoherence is strong in high-energy electron scattering from
amorphous samples. The fading of fringes with increasing layer separation
indicates an effective illumination coherence length of about 225 nm, which is
consistent with the value of 270 nm expected for the heated Schottky field
emitter source. A small reduction in measured coherence length is expected
because of the additional energy spread induced in the beam after it passes
through the first layer.
PMID- 26428441
TI - Which hospitalisations are ambulatory care-sensitive, to what degree, and how
could the rates be reduced? Results of a group consensus study in Germany.
AB - BACKGROUND: Much has been written lately regarding hospitalisations for
ambulatory care-sensitive conditions (ACSH) and their strengths and weaknesses as
a quality management indicator. The idea underlying ambulatory care-sensitive
conditions (ACSC) is that effective treatment of acute conditions, good
management of chronic illnesses and immunisation against infectious diseases can
reduce the risk of a specified set of hospitalisations. METHODS: The present
paper applies group consensus methods to synthesise available evidence with
expert opinion, thus identifying relevant ACSC. It contributes to the literature
by evaluating the degree of preventability of ACSH and surveying the medical and
systemic changes needed to increase quality for each diagnosis group. Forty
physicians proportionally selected from all medical disciplines relevant to the
treatment of ACSC participated in the three round Delphi survey. The setting of
the study is Germany. RESULTS: The proposed core list is a subset of 22 ACSC
diagnosis groups, covering 90% of all consented ACSH and conditions with a higher
than 85% estimated degree of preventability. Of all 18.6 million German hospital
cases in the year 2012, the panelists considered 5.04 million hospitalisations
(27%) to be sensitive to ambulatory care, of which 3.72 (20%) were estimated to
be actually preventable. If only emergencies are considered, the ACSH share
reduces to less than 8%. The geographic distribution of ACSH indicates
significant regional variation with particularly high rates and potential for
improvement in the North Rhine region, in Thuringia, Saxony-Anhalt, northern and
eastern Bavaria and the Saarland. The average degree of preventability was 75%
across all diagnosis groups. By far the most often mentioned strategy for
reducing ACSH was 'improving continuous care'. CONCLUSION: There are several good
reasons why process indicators prevail in the assessment of ambulatory care. ACSH
rates can however provide a more complete picture by adding useful information
related to the overall patient outcome. The results of our analysis should be
used to encourage debate and as a basis for further confirmatory work.
PMID- 26428442
TI - Physical employment standards for U.K. fire and rescue service personnel.
AB - BACKGROUND: Evidence-based physical employment standards are vital for
recruiting, training and maintaining the operational effectiveness of personnel
in physically demanding occupations. AIMS: (i) Develop criterion tests for in
service physical assessment, which simulate the role-related physical demands of
UK fire and rescue service (UK FRS) personnel. (ii) Develop practical physical
selection tests for FRS applicants. (iii) Evaluate the validity of the selection
tests to predict criterion test performance. METHODS: Stage 1: we conducted a
physical demands analysis involving seven workshops and an expert panel to
document the key physical tasks required of UK FRS personnel and to develop
'criterion' and 'selection' tests. Stage 2: we measured the performance of 137
trainee and 50 trained UK FRS personnel on selection, criterion and 'field'
measures of aerobic power, strength and body size. Statistical models were
developed to predict criterion test performance. Stage 3: matter experts derived
minimum performance standards. RESULTS: We developed single person simulations of
the key physical tasks required of UK FRS personnel as criterion and selection
tests (rural fire, domestic fire, ladder lift, ladder extension, ladder climb,
pump assembly, enclosed space search). Selection tests were marginally stronger
predictors of criterion test performance (r = 0.88-0.94, 95% Limits of Agreement
[LoA] 7.6-14.0%) than field test scores (r = 0.84-0.94, 95% LoA 8.0-19.8%) and
offered greater face and content validity and more practical implementation.
CONCLUSIONS: This study outlines the development of role-related, gender-free
physical employment tests for the UK FRS, which conform to equal opportunities
law.
PMID- 26428443
TI - Coping patterns in special school staff: demographic and organizational factors.
AB - BACKGROUND: Teachers' mental health is commonly discussed in organizational
health studies, but studies in special schools are rare. Work-related coping and
experience patterns (WCEPs) have been shown to be associated with mental health
and intentions to leave. The influence of organizational factors on coping
patterns has not been examined. AIMS: To assess the distribution of WCEPs in
special school staff and to identify potential influencing factors. METHODS: We
surveyed a sample of teachers and educational staff in 13 German special schools
using the WCEP questionnaire and COPSOQ (Copenhagen Psychosocial Questionnaire).
RESULTS: Of 245 teachers and 417 educational staff contacted, 114 teachers (47%)
and 252 educational staff (60%) responded, an overall response rate of 55%
(366/662). Coping patterns of special school staff were classified as unambitious
(30%), excessively ambitious (7%), resigned (17%), healthy-ambitious (12%) or
unclassifiable (34%). Furthermore we found several significant relations with
demographic and organizational factors. For example, the resigned pattern is
associated with age [Exp(B) 1.12; 95% CI 1.05-1.19], emotional demands [Exp(B)
1.07; 95% CI 1.01-1.12], work-family conflict [Exp(B) 1.07; 95% CI 1.03-1.10] and
bullying [Exp(B) 1.04; 95% CI 1.00-1.08]. CONCLUSIONS: Since emotional and social
factors are associated with risky (excessively ambitious or resigned) and
unambitious coping patterns in special school teachers and educational staff,
interventions should focus on them. Further research could explore causal
relations and observe the development of coping styles over time.
PMID- 26428444
TI - Outcome of hemiplegic cerebral palsy born at term depends on its etiology.
AB - OBJECTIVES: To elucidate the etiology and its relationship to the outcomes of
hemiplegic cerebral palsy (HCP). PARTICIPANTS AND METHODS: MR images and outcomes
of 156 children with HCP born at term and older than three years were
investigated in two major centers for cerebral palsy in Japan. Etiologies were
classified into perinatal ischemic stroke (PIS), cerebral dysgenesis (CD), and
others. PIS was divided into periventricular venous infarction (PVI) and two
types of arterial infarction; middle cerebral artery infarction (MCAI) and deep
gray matter infarction (DGMI). Initial signs and the time of presentation were
investigated among the three types of PIS. As functional outcomes, laterality of
paresis, age at initial walk, affected hand's function, intellectual development,
and occurrence of epilepsy were compared among all the four types. RESULTS:
ETIOLOGY: PIS was found in 106 children (68%), while CD accounted for 28 (18%).
Among PIS, venous infarction was more common than arterial infarction (62:44).
OUTCOMES: PVI revealed later presentation of motor asymmetry and more involvement
of lower extremity as the initial sign among PIS groups. Only MCAI showed right
side predominance in laterality of paresis. DGMI related to better intellectual
development and PVI showed lower occurrence of epilepsy, while there was no
significant difference in affected hand's function among the four groups. PIS
groups showed significantly earlier attainment of independent walk, better
intellectual development, and lower occurrence of epilepsy than CD. CONCLUSIONS:
PVI was the most common cause of HCP born at term, and the etiology closely
related to the initial signs of hemiplegia and overall outcomes.
PMID- 26428445
TI - Positive Affect and Health Behaviors Across 5 Years in Patients With Coronary
Heart Disease: The Heart and Soul Study.
AB - OBJECTIVES: Positive psychological states are linked to superior health and
longevity, possibly due to behavioral factors. We evaluated cross-sectional and 5
year associations between positive affect and health behaviors in patients with
coronary heart disease (CHD). METHODS: Outpatients with CHD reported positive
affect, physical activity, sleep quality, medication adherence, cigarette
smoking, and alcohol use at baseline (n = 1022) and 5 years later (n = 662).
Covariates in regression analyses included demographics, cardiac disease
severity, and depressive symptoms. RESULTS: At baseline, higher positive affect
(per 1 standard deviation) was associated with better health behaviors: physical
activity (odds ratio [OR] = 1.52, 95% 95% confidence interval [CI] = 1.30-1.77, p
< .001), sleep quality (OR = 1.24, 95% CI = 1.04-1.48, p = .015), medication
adherence (OR = 1.46, 95% CI = 1.12-1.90, p = .005), and nonsmoking (OR = 1.29,
95% CI = 1.06-1.57, p = .012), but was unrelated to alcohol use. Baseline
positive affect did not predict health behaviors at follow-up, accounting for
baseline behaviors. However, increases in positive affect across 5 years co
occurred with improvements in physical activity (B = 0.023, standard error [SE] =
0.008, p = .002), sleep quality (B = 0.011, SE = 0.005, p = .039), and medication
adherence (B = 0.014, SE = 0.004, p < .001), but not smoking status (OR = 1.07,
95% CI = 0.73-1.55, p = .74). CONCLUSIONS: Positive affect was associated with
health behaviors among patients with CHD. Efforts to sustain or enhance positive
affect may be promising for promoting better health behaviors.
PMID- 26428446
TI - The Intestinal Microbiota in Acute Anorexia Nervosa and During Renourishment:
Relationship to Depression, Anxiety, and Eating Disorder Psychopathology.
AB - OBJECTIVE: The relevance of the microbe-gut-brain axis to psychopathology is of
interest in anorexia nervosa (AN), as the intestinal microbiota plays a critical
role in metabolic function and weight regulation. METHODS: We characterized the
composition and diversity of the intestinal microbiota in AN, using stool samples
collected at inpatient admission (T1; n = 16) and discharge (T2; n = 10). At T1,
participants completed the Beck Depression and Anxiety Inventories and the Eating
Disorder Examination-Questionnaire. Patients with AN were compared with healthy
individuals who participated in a previous study (healthy comparison group; HCG).
Genomic DNA was isolated from stool samples, and bacterial composition was
characterized by 454 pyrosequencing of the 16S rRNA gene. Sequencing results were
processed by the Quantitative Insights Into Microbial Ecology pipeline. We
compared T1 versus T2 samples, samples from both points were compared with HCG (n
= 12), and associations between psychopathology and T1 samples were explored.
RESULTS: In patients with AN, significant changes emerged between T1 and T2 in
taxa abundance and beta (between-sample) diversity. Patients with AN had
significantly lower alpha (within-sample) diversity than did HCG at both T1 (p =
.0001) and T2 (p = .016), and differences in taxa abundance were found between AN
patients and HCG. Levels of depression, anxiety, and eating disorder
psychopathology at T1 were associated with composition and diversity of the
intestinal microbiota. CONCLUSIONS: We provide evidence of an intestinal
dysbiosis in AN and an association between mood and the enteric microbiota in
this patient population. Future directions include mechanistic investigations of
the microbe-gut-brain axis in animal models and association of microbial measures
with metabolic changes and recovery indices.
PMID- 26428447
TI - Myoclonus in the critically ill: Diagnosis, management, and clinical impact.
AB - Myoclonus is the second most common involuntary non-epileptic movement in
intensive care units following tremor-like gestures. Although there are several
types of myoclonus, they remain underappreciated, and their diagnostic and
prognostic associations are largely ignored. This review discusses clinical,
electrophysiological, neuroanatomical, and neuroimaging characteristics of
different types of myoclonus in critically ill adults along with their prognostic
impact and treatment options. Myoclonus is characterized by a sudden, brief, and
sometimes repetitive muscle contraction of body parts, or a brief and sudden
cessation of tonic muscle innervation followed by a rapid recovery of tonus.
Myoclonus can resemble physiologic and other pathologic involuntary movements.
Neurologic injuries, anesthetics, and muscle relaxants interfere with the typical
appearance of myoclonus. Identifying "real myoclonus" and determining the
neuroanatomical origin are important, as treatment responses depend on the
involved neuroanatomical structures. The identification of the type of myoclonus,
the involved neuroanatomical structures, and the associated illnesses is
essential to direct treatment. In conclusion, the combined clinical,
electrophysiological, and neuroradiological examination reliably uncovers the
neuroanatomical sources and the pathophysiology of myoclonus. Recognizing
cortical myoclonus is critical, as it is treatable and may progress to
generalized convulsive seizures or status epilepticus.
PMID- 26428448
TI - Echocardiography for adult patients supported with extracorporeal membrane
oxygenation.
AB - Venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO)
support is increasingly being used in recent years in the adult population. Owing
to the underlying disease precipitating severe respiratory or cardiac failure,
echocardiography plays an important role in the management of these patients.
Nevertheless, there are currently no guidelines on the use of echocardiography in
the setting of ECMO support. This review describes the current state of
application of echocardiography for patients supported with both VA and VV ECMO.
PMID- 26428449
TI - Lysate of engineered Escherichia coli supports high-level conversion of glucose
to 2,3-butanediol.
AB - Cell-free metabolic engineering (CFME) is emerging as a powerful approach for the
production of target molecules and pathway debugging. Unfortunately, high
cofactor costs, limited cofactor and energy regeneration, and low volumetric
productivities hamper the widespread use and practical implementation of CFME
technology. To address these challenges, we have developed a cell-free system
that harnesses ensembles of catalytic proteins prepared from crude lysates, or
extracts, of cells to fuel highly active heterologous metabolic conversions. As a
model pathway, we selected conversion of glucose to 2,3-butanediol (2,3-BD), a
medium level commodity chemical with many industrial applications. Specifically,
we engineered a single strain of Escherichia coli to express three pathway
enzymes necessary to make meso-2,3-BD (m2,3-BD). We then demonstrated that
lysates from this strain, with addition of glucose and catalytic amounts of
cofactors NAD+ and ATP, can produce m2,3-BD. Endogenous glycolytic enzymes
convert glucose to pyruvate, the starting intermediate for m2,3-BD synthesis.
Strikingly, with no strain optimization, we observed a maximal synthesis rate of
m2,3-BD of 11.3 +/- 0.1 g/L/h with a theoretical yield of 71% (0.36 g m2,3-BD/g
glucose) in batch reactions. Titers reached 82 +/- 8 g/L m2,3-BD in a 30 h fed
batch reaction. Our results highlight the ability for high-level co-factor
regeneration in cell-free lysates. Further, they suggest exciting opportunities
to use lysate-based systems to rapidly prototype metabolic pathways and carry out
molecular transformations when bioconversion yields (g product/L), productivities
(g product/L/h), or cellular toxicity limit commercial feasibility of whole-cell
fermentation.
PMID- 26428451
TI - Whole organism blood stage vaccines against malaria.
AB - Despite a century of research focused on the development and implementation of
effective control strategies, infection with the malaria parasite continues to
result in significant morbidity and mortality worldwide. An effective malaria
vaccine is considered by many to be the definitive solution. Yet, after decades
of research, we are still without a vaccine that is capable of inducing robust,
long lasting protection in naturally exposed individuals. Extensive sub-unit
vaccine development focused on the blood stage of the malaria parasite has thus
far yielded disappointing results. There is now a renewed focus on whole parasite
vaccine strategies, particularly as they may overcome some of the inherent
weaknesses deemed to be associated with the sub-unit approach. This review
discusses the whole parasite vaccine strategy focusing on the blood stage of the
malaria parasite, with an emphasis on recent advances and challenges in the
development of killed and live attenuated vaccines.
PMID- 26428452
TI - Promoting Tdap immunization in pregnancy: Associations between maternal
perceptions and vaccination rates.
AB - OBJECTIVE: Tdap vaccine uptake among US pregnant women is low despite current
recommendations. This study evaluated if a Tdap vaccine information statement
(VIS) affected overall perception, vaccination intention, and components of a
health behavior model associated with Tdap vaccination rates. METHODS: A
randomized, prospective study was conducted among pregnant women receiving care
at two women's clinics in May-August 2014. Verbally consented participants were
randomized to receive either the standard CDC Tdap VIS (sVIS) or a modified
version (mVIS) before completing the first multi-part survey (T1). After T1,
participants read their assigned VIS then completed the second part (T2). A 2015
chart review identified vaccinated participants. A health behavior model was
hypothesized using the Reasoned Action Approach and Health Belief Model. Logistic
regression, path analysis, and chi-square tests were used in the analysis.
RESULTS: 279 surveys were analyzed. Average age of the participants was 26.4
years (SD=5.7) with average gestational age of 25.9 weeks (SD=9.2). 13% self
reported receiving Tdap vaccine prior to the survey. Overall perception scores
significantly increased (3.1-3.4, p<0.001) after VIS review. A chart review
showed that 131 (47%) received the vaccine post study. There was no significant
difference in vaccination rates between the sVIS and mVIS groups (45% vs. 49%).
Perceived benefits (B=0.315) and self-efficacy (B=0.197) were positively
associated with the overall perception (T1), while perceived barriers (B=-0.191)
were negatively associated with the overall perception (T1). Social norms
(B=0.230), self-efficacy (B=0.213), and perceived benefits (B=0.117) were
positively associated with vaccination intention (T1). The vaccination intention
(T2) was positively associated with participants' decision to receive Tdap
vaccine (B=0.223). CONCLUSION: A VIS improved overall perception of the Tdap
vaccine. Vaccination intention was a predictor of Tdap vaccination. It is crucial
to provide information about immunization benefits to promote maternal Tdap
vaccination.
PMID- 26428450
TI - Impact of the learning curve on procedural results and acute outcome after
percutaneous coronary interventions with everolimus-eluting bioresorbable
scaffolds in an all-comers population.
AB - BACKGROUND/PURPOSE: The implantation of bioresorbable scaffolds (BVSs) is an
emerging technique in the treatment of coronary lesions and implantation of BVSs
is different than that of metallic drug-eluting stents, however, due to different
mechanical properties. This investigation focused on procedural and mid-term
results and was designed to evaluate whether there is evidence of a learning
curve with BVSs and how it might influence the clinical outcome.
METHODS/MATERIALS: In an all-comers registry, the first 100 consecutive patients
were compared with the second 100 patients. Target parameters were major adverse
cardiac events (MACEs), including cardiac death, any myocardial infarction, and
percutaneous or surgical target lesion revascularization (TLR). Target vessel
failure (TVF) comprised cardiac death, target vessel myocardial infarction, and
percutaneous or surgical target vessel revascularization (TVR). RESULTS: Baseline
characteristics were not significantly different. Post-dilatation was used
significantly more often in the second group (23.8% vs. 50.5%, p<0.05) as was
intravascular imaging (9% vs. 19%, p<0.05). In-hospital MACEs (2.0% for both
groups) and median duration of hospital stay (4 (2-6)days) did not differ
significantly. During a follow-up of 210 (155-369) or 200 (176-286)days (p=n.s.)
for the first and second groups, respectively, MACE (11.2% vs. 1.1%, p<0.01), TVF
(10.1% vs. 1.1%, p<0.01), and TVR (9.9% vs. 1.1%, p<0.05) rates were
significantly lower in the second group. CONCLUSION: There is evidence of a
learning curve. Post-dilatation is most probably associated with an improved
clinical result and intravascular imaging might be useful for further
improvement.
PMID- 26428453
TI - Development of vaccines for Plasmodium vivax malaria.
AB - Plasmodium vivax continues to cause significant morbidity outside Africa with
more than 50% of malaria cases in many parts of South and South-east Asia,
Pacific islands, Central and South America being attributed to P. vivax
infections. The unique biology of P. vivax, including its ability to form latent
hypnozoites that emerge months to years later to cause blood stage infections,
early appearance of gametocytes before clinical symptoms are apparent and a
shorter development cycle in the vector makes elimination of P. vivax using
standard control tools difficult. The availability of an effective vaccine that
provides protection and prevents transmission would be a valuable tool in efforts
to eliminate P. vivax. Here, we review the latest developments related to P.
vivax malaria vaccines and discuss the challenges as well as directions toward
the goal of developing highly efficacious vaccines against P. vivax malaria.
PMID- 26428454
TI - A study of different buffers to maximize viability of an oral Shigella vaccine.
AB - Live, whole cell killed and subunit vaccines are being developed for diarrheal
diseases caused by V. cholerae, Shigella species, ETEC, and Campylobacter. Some
of these vaccines can be administered orally since this route best mimics natural
infection. Live vaccines administered orally have to be protected from the harsh
acidic gastric environment. Milk and bicarbonate solutions have been administered
to neutralize the stomach acid. For many Shigella vaccine trials, 100-120 ml of a
bicarbonate solution is ingested followed by the live vaccine candidate, which is
delivered in 30 ml of bicarbonate, water or saline. It is not clear if maximum
bacterial viability is achieved under these conditions. Also, volumes of
neutralizing buffer that are optimal for adults may be unsuitable for children
and infants. To address these questions, we performed studies to determine the
viability and stability of a Shigella sonnei vaccine candidate, WRSS1, in a
mixture of different volumes of five different buffer solutions added to
hydrochloric acid to simulate gastric acidity. Among the buffers tested,
bicarbonate solution, rotavirus buffer and CeraVacx were better at neutralizing
acid and maintaining the viability of WRSS1. Also, a much smaller volume of the
neutralizing buffer was sufficient to counteract stomach acid while maintaining
bacterial viability.
PMID- 26428455
TI - Optimal attenuation of a PR8-derived mouse pathogenic H5N1 recombinant virus for
testing antigenicity and protective efficacy in mice.
AB - The PR8-based reverse genetics vector system is widely used to generate
commercial vaccine strains, but the pathogenicity of PR8-derived recombinant
viruses in mice hinders further immunological studies. In the present study, we
generated PR8-derived H5N1 recombinant viruses, in which haemagglutinin (HA) and
neuraminidase (NA) originated from a mouse-pathogenic H5N1 low pathogenic avian
influenza virus (LPAIV), and the non-structural proteins (NS) and polymerase
basic protein 2 (PB2) originated from different H9N2 LPAIVs. In contrast to the
control H5N1 recombinant virus, harboring six internal genes from PR8, the NS and
PB2 recombinant viruses did not cause body weight loss in mice. However, the NS
recombinant virus replicated in the lungs of mice. It was more immunogenic than
the PB2 recombinant virus to protect efficiently against a lethal challenge of a
H5N1 highly pathogenic AIV with 89 and 88% amino acid identity in HA and NA,
respectively. Therefore, the NS gene may be useful for generating nonpathogenic
and immunogenic PR8-derived recombinant viruses for studies of antigenicity and
protective efficacy in mice.
PMID- 26428456
TI - Novel pseudorabies virus variant with defects in TK, gE and gI protects growing
pigs against lethal challenge.
AB - One of the distinct features of the emerging Chinese pseudorabies virus (PRV)
variant is its ability to cause severe neurological signs and high mortality in
growing pigs in Bartha-K61-vaccinated pig farms. Either single- or multiple-gene
deleted live vaccine candidates have been developed; however, none was evaluated
thoroughly in growing pigs. Here, we generated rSMXDeltagI/gEDeltaTK, an
attenuated PRV variant with defects in TK, gI and gE genes. The growth kinetics
of the attenuated virus was similar to the wild type (wt) strain. It was safe for
1-day-old piglets. Twenty one-day-old weaned pigs were immunized intramuscularly
either with 10(6.0) TCID50 of rSMXDeltagI/gEDeltaTK or one dose of commercial
Bartha-K61 vaccine, or with DMEM, and were challenged intranasally with 10(7.0)
TCID50 wt virus at 28 days post vaccination. rSMXDeltagI/gEDeltaTK elicited
higher level neutralization antibody against both PRV variant SMX and Bartha-K61
strain, while Bartha-K61 vaccine elicited lower neutralization activity of
antibody against SMX. After challenge, all pigs in rSMXDeltagI/gEDeltaTK group
survived without any clinical signs, while unvaccinated group showed 100%
mortality, and Bartha-K61 group showed severe respiratory symptoms and 3 out of 5
pigs exhibited severe neurological signs. Pigs in rSMXDeltagI/gEDeltaTK group
gained significantly higher body weight and diminished viral excretion titer and
period, compared with Bartha-K61 group. Furthermore, the safety and efficacy of
rSMXDeltagI/gEDeltaTK was also evaluated in sheep and compared with local vaccine
in growing pigs. These data suggest that the attenuated strain
rSMXDeltagI/gEDeltaTK is a promising live marker vaccine candidate for PR control
in the context of emerging PRV variants.
PMID- 26428457
TI - Hit-and-run, hit-and-stay, and commensal bacteria present different peptide
content when viewed from the perspective of the T cell.
AB - Different types of bacteria face different pressures from the immune system, with
those that persist ("hit-and-stay") potentially having to adapt more in order to
escape than those prone to short-lived infection ("hit-and-run"), and with
commensal bacteria potentially different from both due to additional physical
mechanisms for avoiding immune detection. The Janus Immunogenicity Score (JIS)
was recently developed to assess the likelihood of T cell recognition of an
antigen, using an analysis that considers both binding of a peptide within the
antigen by major histocompatability complex (MHC) and recognition of the
peptide:MHC complex by cognate T cell receptor (TCR). This score was shown to be
predictive of T effector vs. T regulatory or null responses in experimental data,
as well as to distinguish viruses representative of the hit-and-stay vs. hit-and
run phenotypes. Here, JIS-based analyses were conducted in order to characterize
the extent to which the pressure to avoid T cell recognition is manifested in
genomic differences among representative hit-and-run, hit-and-stay, and commensal
bacteria. Overall, extracellular proteins were found to have different JIS
profiles from cytoplasmic ones. Contrasting the bacterial groups, extracellular
proteins were shown to be quite different across the groups, much more so than
intracellular proteins. The differences were evident even at the level of
corresponding peptides in homologous protein pairs from hit-and-run and hit-and
stay bacteria. The multi-level analysis of patterns of immunogenicity across
different groups of bacteria provides a new way to approach questions of
bacterial immune camouflage or escape, as well as to approach the selection and
optimization of candidates for vaccine design.
PMID- 26428459
TI - Assessing the relationship between neighborhood factors and diabetes related
health outcomes and self-care behaviors.
AB - BACKGROUND: Studies have shown that community and neighborhood characteristics
can impact health outcomes of those with chronic illness, including T2DM.
Factors, such as crime, violence, and lack of resources have been shown to be
barriers to optimal health outcomes in diabetes. Thus, the objective of this
study is to assess the effects of neighborhood factors on diabetes-related health
outcomes and self-care behaviors. METHODS: Adult patients (N = 615) with type 2
diabetes mellitus (T2DM) were recruited from an academic medical center and a
Veterans Affairs medical center in the southeastern United States. Validated
scales and indices were used to assess neighborhood factors and diabetes-related
self-care behaviors. The most recent HbA1c, blood pressure, and LDL cholesterol
were abstracted from each patients' electronic medical record. RESULTS: In the
fully adjusted model, significant associations were between neighborhood
aesthetics and diabetes knowledge (beta = 0.141) and general diet (beta =
0.093); neighborhood comparison and diabetes knowledge (beta = 0.452);
neighborhood activities and general diet (beta = -0.072), exercise (beta =
0.104), and foot care (beta = -0.114); food insecurity and medication adherence
(beta = -0.147), general diet (beta = -0.125), and blood sugar testing (beta =
0.172); and social support and medication adherence (beta = 0.009), foot care
(beta = 0.010), and general diet (beta = 0.016). Significant associations were
also found between neighborhood violence and LDL Cholesterol (beta = 4.04),
walking environment and exercise (beta = -0.040), and social cohesion and HbA1c
(beta = -0.086). DISCUSSION: We found that neighborhood violence, aesthetics,
walking environment, activities, food insecurity, neighborhood comparison, social
cohesion and social support have statistically significant associations with self
care behaviors and outcomes to varying degrees. However, the key neighborhood
factors that had independent associations with multiple self-care behaviors and
outcomes were food insecurity, neighborhood activities and social support.
CONCLUSION: This study suggests that food insecurity, neighborhood activities,
aesthetics, and social support may be important targets for interventions in
individuals with T2DM.
PMID- 26428458
TI - Large screen approaches to identify novel malaria vaccine candidates.
AB - Until recently, malaria vaccine development efforts have focused almost
exclusively on a handful of well characterized Plasmodium falciparum antigens.
Despite dedicated work by many researchers on different continents spanning more
than half a century, a successful malaria vaccine remains elusive. Sequencing of
the P. falciparum genome has revealed more than five thousand genes, providing
the foundation for systematic approaches to discover candidate vaccine antigens.
We are taking advantage of this wealth of information to discover new antigens
that may be more effective vaccine targets. Herein, we describe different
approaches to large-scale screening of the P. falciparum genome to identify
targets of either antibody responses or T cell responses using human specimens
collected in Controlled Human Malaria Infections (CHMI) or under conditions of
natural exposure in the field. These genome, proteome and transcriptome based
approaches offer enormous potential for the development of an efficacious malaria
vaccine.
PMID- 26428460
TI - Coronary risk in relation to genetic variation in MEOX2 and TCF15 in a Flemish
population.
AB - BACKGROUND: In mice MEOX2/TCF15 heterodimers are highly expressed in heart
endothelial cells and are involved in the transcriptional regulation of lipid
transport. In a general population, we investigated whether genetic variation in
these genes predicted coronary heart disease (CHD). RESULTS: In 2027 participants
randomly recruited from a Flemish population (51.0 % women; mean age 43.6 years),
we genotyped six SNPs in MEOX2 and four in TCF15. Over 15.2 years (median), CHD,
myocardial infarction, coronary revascularisation and ischaemic cardiomyopathy
occurred in 106, 53, 78 and 22 participants. For SNPs, we contrasted CHD risk in
minor-allele heterozygotes and homozygotes (variant) vs. major-allele homozygotes
(reference) and for haplotypes carriers (variant) vs. non-carriers. In
multivariable-adjusted analyses with correction for multiple testing, CHD risk
was associated with MEOX2 SNPs (P <= 0.049), but not with TCF15 SNPs (P >= 0.29).
The MEOX2 GTCCGC haplotype (frequency 16.5 %) was associated with the sex- and
age-standardised CHD incidence (5.26 vs. 3.03 events per 1000 person-years; P =
0.036); the multivariable-adjusted hazard ratio [HR] of CHD was 1.78 (95 %
confidence interval, 1.25-2.56; P = 0.0054). For myocardial infarction, coronary
revascularisation, and ischaemic cardiomyopathy, the corresponding HRs were 1.96
(1.16-3.31), 1.87 (1.20-2.91) and 3.16 (1.41-7.09), respectively. The MEOX2
GTCCGC haplotype significantly improved the prediction of CHD over and beyond
traditional risk factors and was associated with similar population-attributable
risk as smoking (18.7 % vs. 16.2 %). CONCLUSIONS: Genetic variation in MEOX2, but
not TCF15, is a strong predictor of CHD. Further experimental studies should
elucidate the underlying molecular mechanisms.
PMID- 26428461
TI - A stapled peptide antagonist of MDM2 carried by polymeric micelles sensitizes
glioblastoma to temozolomide treatment through p53 activation.
AB - Antagonizing MDM2 and MDMX to activate the tumor suppressor protein p53 is an
attractive therapeutic paradigm for the treatment of glioblastoma multiforme
(GBM). However, challenges remain with respect to the poor ability of p53
activators to efficiently cross the blood-brain barrier and/or blood-brain tumor
barrier and to specifically target tumor cells. To circumvent these problems, we
developed a cyclic RGD peptide-conjugated poly(ethylene glycol)-co-poly(lactic
acid) polymeric micelle (RGD-M) that carried a stapled peptide antagonist of both
MDM2 and MDMX (sPMI). The peptide-carrying micelle RGD-M/sPMI was prepared via
film-hydration method with high encapsulation efficiency and loading capacity as
well as ideal size distribution. Micelle encapsulation dramatically increased the
solubility of sPMI, thus alleviating its serum sequestration. In vitro studies
showed that RGD-M/sPMI efficiently inhibited the proliferation of glioma cells in
the presence of serum by activating the p53 signaling pathway. Further, RGD
M/sPMI exerted potent tumor growth inhibitory activity against human glioblastoma
in nude mouse xenograft models. Importantly, the combination of RGD-M/sPMI and
temozolomide--a standard chemotherapy drug for GBM increased antitumor efficacy
against glioblastoma in experimental animals. Our results validate a combination
therapy using p53 activators with temozolomide as a more effective treatment for
GBM.
PMID- 26428462
TI - Liposome-based glioma targeted drug delivery enabled by stable peptide ligands.
AB - The treatment of glioma is one of the most challenging tasks in clinic. As an
intracranial tumor, glioma exhibits many distinctive characteristics from other
tumors. In particular, various barriers including enzymatic barriers in the blood
and brain capillary endothelial cells, blood-brain barrier (BBB) and blood-brain
tumor barrier (BBTB) rigorously prevent drug and drug delivery systems from
reaching the tumor site. To tackle this dilemma, we developed a liposomal
formulation to circumvent multiple-barriers by modifying the liposome surface
with proteolytically stable peptides, (D)CDX and c(RGDyK). (D)CDX is a D-peptide
ligand of nicotine acetylcholine receptors (nAChRs) on the BBB, and c(RGDyK) is a
ligand of integrin highly expressed on the BBTB and glioma cells. Lysosomal
compartments of brain capillary endothelial cells are implicated in the
transcytosis of those liposomes. However, both peptide ligands displayed
exceptional stability in lysosomal homogenate, ensuring that intact ligands could
exert subsequent exocytosis from brain capillary endothelial cells and glioma
targeting. In the cellular uptake studies, dually labeled liposomes could target
both brain capillary endothelial cells and tumor cells, effectively traversing
the BBB and BBTB monolayers, overcoming enzymatic barrier and targeting three
dimensional tumor spheroids. Its targeting ability to intracranial glioma was
further verified in vivo by ex vivo imaging and histological studies. As a
result, doxorubicin liposomes modified with both (D)CDX and c(RGDyK) presented
better anti-glioma effect with prolonged median survival of nude mice bearing
glioma than did unmodified liposomes and liposomes modified with individual
peptide ligand. In conclusion, the liposome suggested in the present study could
effectively overcome multi-barriers and accomplish glioma targeted drug delivery,
validating its potential value in improving the therapeutic efficacy of
doxorubicin for glioma.
PMID- 26428463
TI - Reply: To PMID 25823770.
PMID- 26428464
TI - White light endoscopy versus chromoendoscopy for the detection of dysplasia
during inflammatory bowel disease surveillance with colonoscopy.
PMID- 26428465
TI - Defining the relationship between clinical and biochemical disease activity
indices and perceived stress in inflammatory bowel disease.
PMID- 26428466
TI - Reply: To PMID 26077178.
PMID- 26428467
TI - Effects of education to facilitate knowledge about chronic pain for adults: a
systematic review with meta-analysis.
AB - BACKGROUND: Chronic pain can contribute to disability, depression, anxiety, sleep
disturbances, poor quality of life and increased health care costs, with close to
20 % of the adult population in Europe reporting chronic pain. To empower the
person to self-manage, it is advocated that education and training about the
nature of pain and its effects and how to live with pain is provided. The
objective of this review is to determine the level of evidence for education to
facilitate knowledge about chronic pain, delivered as a stand-alone intervention
for adults, to reduce pain and disability. METHODS: We identified randomised
controlled trials of educational intervention for chronic pain by searching
CENTRAL, MEDLINE, EMBASE and ongoing trials registries (inception to December
2013). Main inclusion criteria were (1) pain >3 months; (2) study design that
allowed isolation of effects of education and (3) measures of pain or disability.
Two reviewers independently screened and appraised each study. RESULTS: Nine
studies were analysed. Pooled data from five studies, where the comparator group
was usual care, showed no improvement in pain or disability. In the other four
studies, comparing different types of education, there was no evidence for an
improvement in pain; although, there was evidence (from one study) of a decrease
in disability with a particular form of education-pain neurophysiology education
(PNE). Post-hoc analysis of psychosocial outcomes reported in the studies showed
evidence of a reduction in catastrophising and an increase of knowledge about
pain following PNE. CONCLUSIONS: The evidence base is limited by the small
numbers of studies, their relatively small sample sizes, and the diversity in
types of education studied. From that limited evidence, the only support for this
type of education is for PNE, though it is insufficiently strong to recommend
conclusively that PNE should be delivered as a stand-alone intervention. It
therefore remains sensible to recommend that education be delivered in
conjunction with other pain management approaches as we cannot confidently
conclude that education alone is effective in reducing pain intensity or related
disability in chronic pain in adults.
PMID- 26428470
TI - An interview with David Sackett, 2014-2015.
PMID- 26428468
TI - Saturation pulse design for quantitative myocardial T1 mapping.
AB - BACKGROUND: Quantitative saturation-recovery based T1 mapping sequences are less
sensitive to systematic errors than the Modified Look-Locker Inversion recovery
(MOLLI) technique but require high performance saturation pulses. We propose to
optimize adiabatic and pulse train saturation pulses for quantitative T1 mapping
to have <1 % absolute residual longitudinal magnetization (|MZ/M0|) over ranges
of B0 and [Formula: see text] (B1 scale factor) inhomogeneity found at 1.5 T and
3 T. METHODS: Design parameters for an adiabatic BIR4-90 pulse were optimized for
improved performance within 1.5 T B0 (+/-120 Hz) and [Formula: see text] (0.7
1.0) ranges. Flip angles in hard pulse trains of 3-6 pulses were optimized for
1.5 T and 3 T, with consideration of T1 values, field inhomogeneities (B0 = +/
240 Hz and [Formula: see text]=0.4-1.2 at 3 T), and maximum achievable B1 field
strength. Residual MZ/M0 was simulated and measured experimentally for current
standard and optimized saturation pulses in phantoms and in-vivo human studies.
T1 maps were acquired at 3 T in human subjects and a swine using a SAturation
recovery single-SHot Acquisition (SASHA) technique with a standard 90 degrees -90
degrees -90 degrees and an optimized 6-pulse train. RESULTS: Measured residual
MZ/M0 in phantoms had excellent agreement with simulations over a wide range of
B0 and [Formula: see text]. The optimized BIR4-90 reduced the maximum residual
|MZ/M0| to <1 %, a 5.8* reduction compared to a reference BIR4-90. An optimized 3
pulse train achieved a maximum residual |MZ/M0| <1 % for the 1.5 T optimization
range compared to 11.3 % for a standard 90 degrees -90 degrees -90 degrees pulse
train, while a 6-pulse train met this target for the wider 3 T ranges of B0 and
[Formula: see text]. The 6-pulse train demonstrated more uniform saturation
across both the myocardium and entire field of view than other saturation pulses
in human studies. T1 maps were more spatially homogeneous with 6-pulse train
SASHA than the reference 90 degrees -90 degrees -90 degrees SASHA in both human
and animal studies. CONCLUSIONS: Adiabatic and pulse train saturation pulses
optimized for different constraints found at 1.5 T and 3 T achieved <1 % residual
|MZ/M0| in phantom experiments, enabling greater accuracy in quantitative
saturation recovery T1 imaging.
PMID- 26428471
TI - Atmospheric polycyclic aromatic hydrocarbons in the urban environment:
Occurrence, toxicity and source apportionment.
AB - Polycyclic Aromatic Hydrocarbons (PAHs) represent a major class of toxic
pollutants because of their carcinogenic and mutagenic characteristics. People
living in urban areas are regularly exposed to PAHs because of abundance of their
emission sources. Within this context, this study aimed to: (i) identify and
quantify the levels of ambient PAHs in an urban environment; (ii) evaluate their
toxicity; and (iii) identify their sources as well as the contribution of
specific sources to measured concentrations. Sixteen PAHs were identified and
quantified in air samples collected from Brisbane. Principal Component Analysis -
Absolute Principal Component Scores (PCA-APCS) was used in order to conduct
source apportionment of the measured PAHs. Vehicular emissions, natural gas
combustion, petrol emissions and evaporative/unburned fuel were the sources
identified; contributing 56%, 21%, 15% and 8% of the total PAHs emissions,
respectively, all of which need to be considered for any pollution control
measures implemented in urban areas.
PMID- 26428472
TI - The Vanderbilt Head and Neck Symptom Survey Brazilian Portuguese version 2.0
(VHNSS 2.0): psychometric properties for patients with head and neck cancer who
have undergone radiotherapy.
AB - BACKGROUND: Patients who undergo radiotherapy to treat head and neck cancer can
present with several symptoms, including oral ones. The symptoms are usually
assessed using instruments to evaluate quality of life. However, these
instruments do not really assess oral health outcomes and their functional
implications. The VHNSS 2.0 instrument was developed to be used with head and
neck cancer patients, and has recently been translated and culturally adapted to
be used in Brazil. The purpose of the study was to evaluate the psychometric
properties of the VHNSS 2.0 Brazilian Portuguese version. METHODS: Three
assessment instruments, the Brazilian Portuguese versions of EORTC QLQ-C30, EORTC
H&N 35 and VHNSS 2.0, were answered by 241 head and neck cancer patients, of whom
47 were submitted to the test retest in 5-16 days. The construct validity was
assessed through convergent validation (assuming correlations between VHNSS 2.0
and EORTC), and known group analysis (radiotherapy time, site of tumor, staging
and surgery). Reliability was evaluated by means of Cronbach's alpha and test
retest using the intraclass correlation coefficient. RESULTS: 241 head and neck
cancer patients, median age 58.8, were included in this study. Hypothesized
correlations were confirmed, the comparison among the groups showed differences
in most of the domains. Reliability for the domains of swallowing solids, dry
mouth, mouth pain, mucus, voice, pain and taste/smell presented Cronbach's alpha
values from 0.858 to 0.735 and for the domains of nutrition, swallowing liquids
and teeth, 0.618, 0.620 and 0.670 respectively. The test-retest reliability, for
the domains of the VHNSS 2.0, measured using intraclass correlation coefficient,
ranged from 0.372 to 0.854. CONCLUSION: The VHNSS 2.0 Brazilian Portuguese
version presented good results for the convergent validation and known-group
analyses. It also showed reliability for the Cronbach's alpha and test retest for
most domains.
PMID- 26428474
TI - Systematic donor selection review process improves cardiac transplant volumes and
outcomes.
AB - BACKGROUND: Heart transplant remains the definitive therapy for advanced heart
failure patients but is limited by organ availability. We identified a large
number of donor hearts from our organ procurement organization (OPO) being
exported to other regions. METHODS: We engaged a multidisciplinary team including
transplant surgeons, cardiologists, and our OPO colleagues to identify
opportunities to improve our center-specific organ utilization rate. We performed
a retrospective analysis of donor offers before and after institution of a novel
review process. RESULTS: Each donor offer made to our program was reviewed on a
monthly basis from July 2013 to June 2014 and compared with the previous year.
This review process resulted in a transplant utilization rate of 28% for period 1
versus 49% for period 2 (P = .007). Limiting the analysis to offers from our
local OPO changed our utilization rate from 46% to 75% (P = .02). Transplant
volume increased from 22 to 35 between the 2 study periods. Thirty-day and 1-year
mortality were unchanged over the 2 periods. A total of 58 hearts were refused by
our center and transplanted at other centers. During period 1, the 30-day and 1
year survival rates for recipients of those organs were 98% and 90%,
respectively, comparable with our historical survival data. CONCLUSIONS: The
simple process of systematically reviewing donor turndown events as a group
tended to reduce variability, increase confidence in expanded criteria for
donors, and resulted in improved donor organ utilization and transplant volumes.
PMID- 26428473
TI - Use of human fibrinogen concentrate during proximal aortic reconstruction with
deep hypothermic circulatory arrest.
AB - OBJECTIVE: Human fibrinogen concentrate (HFC) is approved by the Food and Drug
Administration for use at 70 mg/kg to treat congenital afibrinogenemia. We sought
to determine whether this dose of HFC increases fibrinogen levels in the setting
of high-risk bleeding associated with aortic reconstruction and deep hypothermic
circulatory arrest (DHCA). METHODS: This was a prospective, pilot, off-label
study in which 22 patients undergoing elective proximal aortic reconstruction
with DHCA were administered 70 mg/kg HFC upon separation from cardiopulmonary
bypass (CPB). Fibrinogen levels were measured at baseline, just before, and 10
minutes after HFC administration, on skin closure, and the day after surgery. The
primary study outcome was the difference in fibrinogen level immediately after
separation from CPB, when HFC was administered, and the fibrinogen level 10
minutes following HFC administration. Additionally, postoperative thromboembolic
events were assessed as a safety analysis. RESULTS: The mean baseline fibrinogen
level was 317 +/- 49 mg/dL and fell to 235 +/- 39 mg/dL just before separation
from CPB. After HFC administration, the fibrinogen level rose to 331 +/- 41 mg/dL
(P < .001) and averaged 372 +/- 45 mg/dL the next day. No postoperative
thromboembolic complications occurred. CONCLUSIONS: Administration of 70 mg/kg
HFC upon separation from CPB raises fibrinogen levels by approximately 100 mg/dL
without an apparent increase in thrombotic complications during proximal aortic
reconstruction with DHCA. Further prospective study in a larger cohort of
patients will be needed to definitively determine the safety and evaluate the
efficacy of HFC as a hemostatic adjunct during these procedures.
PMID- 26428475
TI - Utility of Allergy Testing in Patients with Chronic Laryngopharyngeal Symptoms:
Is It Allergic Laryngitis?
AB - OBJECTIVE: To determine the utility of allergy evaluation in patients with
chronic refractory laryngeal symptoms. STUDY DESIGN: Case series with chart
review. SETTING: Tertiary academic medical center. SUBJECTS: All patients who
underwent in vitro allergy testing at a single institution from 2006 to 2010, for
a total of 998 patients. METHODS: Charts of patients who underwent in vitro
allergy testing were identified. The charts were reviewed for the primary
indication for allergy testing, as categorized into rhinitis complaints, chronic
sinusitis, otitis media, and refractory laryngeal symptoms (globus, cough, throat
clearing, increased secretions, and hoarseness). Results of allergy tests and
comorbid conditions were analyzed and compared among groups. RESULTS: The
positive yield of allergy testing in patients with primary laryngeal indications
was 51.8%, 63.3% for rhinitis, 60.9% for sinusitis, and 33.3% for otitis media.
The odds ratio of having a positive test was not statistically different for
patients with laryngeal symptoms, rhinitis, or sinusitis. Patients with chronic
laryngeal symptoms and positive allergy testing were most often sensitized to
dust mites (63%) and least often sensitized to molds (1.3%). CONCLUSIONS: Allergy
testing in patients with chronic laryngeal symptoms yields positive results in
equivalent proportion to patients with other common presenting symptoms. Dust
mites sensitization is the most common sensitization in patients with allergic
laryngitis.
PMID- 26428477
TI - Application of 3-dimensional Modeling to Plan Totally Endoscopic Per-Meatal
Drainage of Petrous Apex Cholesterol Granuloma.
PMID- 26428476
TI - Sensitivity, Specificity, and Posttest Probability of Parotid Fine-Needle
Aspiration: A Systematic Review and Meta-analysis.
AB - OBJECTIVES: (1) To analyze the sensitivity and specificity of fine-needle
aspiration (FNA) in distinguishing benign from malignant parotid disease. (2) To
determine the anticipated posttest probability of malignancy and probability of
nondiagnostic and indeterminate cytology with parotid FNA. DATA SOURCES:
Independently corroborated computerized searches of PubMed, Embase, and Cochrane
Central Register were performed. These were supplemented with manual searches and
input from content experts. REVIEW METHODS: Inclusion/exclusion criteria
specified diagnosis of parotid mass, intervention with both FNA and surgical
excision, and enumeration of both cytologic and surgical histopathologic results.
The primary outcomes were sensitivity, specificity, and posttest probability of
malignancy. Heterogeneity was evaluated with the I(2) statistic. Meta-analysis
was performed via a 2-level mixed logistic regression model. Bayesian nomograms
were plotted via pooled likelihood ratios. RESULTS: The systematic review yielded
70 criterion-meeting studies, 63 of which contained data that allowed for
computation of numerical outcomes (n = 5647 patients; level 2a) and consideration
of meta-analysis. Subgroup analyses were performed in studies that were
prospective, involved consecutive patients, described the FNA technique utilized,
and used ultrasound guidance. The I(2) point estimate was >70% for all analyses,
except within prospectively obtained and ultrasound-guided results. Among the
prospective subgroup, the pooled analysis demonstrated a sensitivity of 0.882
(95% confidence interval [95% CI], 0.509-0.982) and a specificity of 0.995 (95%
CI, 0.960-0.999). The probabilities of nondiagnostic and indeterminate cytology
were 0.053 (95% CI, 0.030-0.075) and 0.147 (95% CI, 0.106-0.188), respectively.
CONCLUSION: FNA has moderate sensitivity and high specificity in differentiating
malignant from benign parotid lesions. Considerable heterogeneity is present
among studies.
PMID- 26428478
TI - Do everyday problems of people with chronic illness interfere with their disease
management?
AB - BACKGROUND: Being chronically ill is a continuous process of balancing the
demands of the illness and the demands of everyday life. Understanding how
everyday life affects self-management might help to provide better professional
support. However, little attention has been paid to the influence of everyday
life on self-management. The purpose of this study is to examine to what extent
problems in everyday life interfere with the self-management behaviour of people
with chronic illness, i.e. their ability to manage their illness. METHODS: To
estimate the effects of having everyday problems on self-management, cross
sectional linear regression analyses with propensity score matching were
conducted. Data was used from 1731 patients with chronic disease(s) who
participated in a nationwide Dutch panel-study. RESULTS: One third of people with
chronic illness encounter basic (e.g. financial, housing, employment) or social
(e.g. partner, children, sexual or leisure) problems in their daily life. Younger
people, people with poor health and people with physical limitations are more
likely to have everyday problems. Experiencing basic problems is related to less
active coping behaviour, while experiencing social problems is related to lower
levels of symptom management and less active coping behaviour. DISCUSSION: The
extent of everyday problems interfering with self-management of people with
chronic illness depends on the type of everyday problems encountered, as well as
on the type of self-management activities at stake. CONCLUSIONS: Healthcare
providers should pay attention to the life context of people with chronic illness
during consultations, as patients' ability to manage their illness is related to
it.
PMID- 26428479
TI - Electronic cigarettes: scarce data and divergent legislations. The need for
evidence-based health policies and research funding.
PMID- 26428480
TI - Investigating the effect of banning non-reduced ignition propensity cigarettes on
fatal residential fires in Sweden.
AB - BACKGROUND: Annually, 100 people die as a result of residential fires in Sweden
and almost a third of the fatal fires are known to be caused by smoking. In an
attempt to reduce the occurrence of these events, reduced ignition propensity
(RIP) cigarettes have been developed. They are designed to reduce the risk of
fire by preventing the cigarette from burning through the full length when left
unattended. In November 2011, a ban was introduced, forbidding the production and
sale of all non-RIP cigarettes in all member states of the European Union,
including Sweden. METHODS: Monthly data on all recorded residential fires and
associated fatalities in Sweden from January 2000 to December 2013 were analyzed
using an interrupted time series design. The effect of the intervention [in
relative risk (RR)] was quantified using generalised additive models for
location, shape and scale. RESULTS: There were no statistically significant
intervention effects on residential fires (RR 0.95 [95% CI: 0.89-1.01]), fatal
residential fires (RR 0.99 [95% CI: 0.80-1.23]), residential fires where smoking
was a known cause (RR 1.10 [95% CI: 0.95-1.28]) or fatal residential fires where
smoking was a known cause (RR 0.92 [95% CI: 0.63-1.35]). CONCLUSION: No evidence
of an effect of the ban on all non-RIP cigarettes on the risk of residential
fires in Sweden was found. The results may not be generalisable to other
countries.
PMID- 26428481
TI - Factors associated with the prevalence of adolescent binge drinking in the urban
areas of Greater Manchester.
AB - Background: Binge drinking in adolescents is a serious problem that has been
recognised for over a generation. On average 61% of students in the European
region had consumed alcohol in the last 30 days and 43% had participated in binge
drinking in the same period. This article investigates the prevalence of
adolescent binge drinking and the factors associated with this prevalence in
urban areas of Greater Manchester. Methods: Data were obtained from the youth
survey of the European Urban Health Indicator System 2 project. Study
participants were school students aged 14-16 from the urban areas of Greater
Manchester. The main outcome measures were adolescent binge drinking prevalence
in Greater Manchester and the socio-demographic factors influencing it. Results:
Greater Manchester had an adolescent binge drinking prevalence of 49.8%.
Individual factors associated with increased prevalence of binge drinking were:
age, substance use, school performance and early initiation of drinking (all
significant at chi2, P < 0.05). Peer factors associated with increased prevalence
of binge drinking were spending evenings with friends, keeping in touch with
friends, having a good relationship with peers and self-reported bullying
behaviours (all significant at chi2, P < 0.05). Family support lowered the
prevalence of adolescent binge drinking. Conduct problems, family affluence and
perceived local crime increased the prevalence of adolescent binge drinking.
Conclusions: Binge drinking is highly prevalent in Greater Manchester
adolescents. Various individual, peer-related, family-related and community
related factors were associated with this problem. Any attempt to tackle the
prevalence of adolescent binge drinking must take into account all of these
factors.
PMID- 26428483
TI - Developing a spinal cord injury research strategy.
PMID- 26428482
TI - Added effect of heat wave on mortality in Seoul, Korea.
AB - A heat wave could increase mortality owing to high temperature. However, little
is known about the added (duration) effect of heat wave from the prolonged period
of high temperature on mortality and different effect sizes depending on the
definition of heat waves and models. A distributed lag non-linear model with a
quasi-Poisson distribution was used to evaluate the added effect of heat wave on
mortality after adjusting for long-term and intra-seasonal trends and apparent
temperature. We evaluated the cumulative relative risk of the added wave effect
on mortality on lag days 0-30. The models were constructed using nine definitions
of heat wave and two relationships (cubic spline and linear threshold model)
between temperature and mortality to leave out the high temperature effect.
Further, we performed sensitivity analysis to evaluate the changes in the effect
of heat wave on mortality according to the different degrees of freedom for time
trend and cubic spline of temperature. We found that heat wave had the added
effect from the prolonged period of high temperature on mortality and it was
considerable in the aspect of cumulative risk because of the lagged influence.
When heat wave was defined with a threshold of 98th percentile temperature and
>=2, 3, and 4 consecutive days, mortality increased by 14.8 % (7.5-22.6, 95 %
confidence interval (CI)), 18.1 % (10.8-26.0, 95 % CI), 18.1 % (10.7-25.9, 95 %
CI), respectively, in cubic spline model. When it came to the definitions of 90th
and 95th percentile, the risk increase in mortality declined to 3.7-5.8 % and 8.6
11.3 %, respectively. This effect was robust to the flexibility of the model for
temperature and time trend, while the definitions of a heat wave were critical in
estimating its relationship with mortality. This finding could help deepen our
understanding and quantifying of the relationship between heat wave and mortality
and select an appropriate definition of heat wave and temperature model in the
future studies.
PMID- 26428484
TI - The Evolution of MALDI-TOF Mass Spectrometry toward Ultra-High-Throughput
Screening: 1536-Well Format and Beyond.
AB - Mass spectrometry (MS) offers a label-free, direct-detection method, in contrast
to fluorescent or colorimetric methodologies. Over recent years, solid-phase
extraction-based techniques, such as the Agilent RapidFire system, have emerged
that are capable of analyzing samples in <10 s. While dramatically faster than
liquid chromatography-coupled MS, an analysis time of 8-10 s is still considered
relatively slow for full-diversity high-throughput screening (HTS). Matrix
assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF)
offers an alternative for high-throughput MS detection. However, sample
preparation and deposition onto the MALDI target, as well as interference from
matrix ions, have been considered limitations for the use of MALDI for screening
assays. Here we describe the development and validation of assays for both small
molecule and peptide analytes using MALDI-TOF coupled with nanoliter liquid
handling. Using the JMJD2c histone demethylase and acetylcholinesterase as model
systems, we have generated robust data in a 1536 format and also increased sample
deposition to 6144 samples per target. Using these methods, we demonstrate that
this technology can deliver fast sample analysis time with low sample volume, and
data comparable to that of current RapidFire assays.
PMID- 26428485
TI - Reliability of Ultrasound Imaging Measures of Transverse Abdominis and Lumbar
Multifidus in Various Positions.
AB - OBJECTIVE: To determine the reliability of measurement of muscle activation via
ultrasound imaging measures of the transverse abdominis (TrA) and lumbar
multifidus (LM) in tabletop, seated, standing, and walking conditions. DESIGN:
Descriptive laboratory study. SETTING: University research laboratory.
PARTICIPANTS: Sixteen healthy participants (age, 20.4 +/- 1.8 years; height,
167.7 +/- 9.0 cm; mass, 65.1 +/- 10.8 kg). INTERVENTIONS: None. MAIN OUTCOME
MEASUREMENTS: The activation ratio (AR) of TrA and LM and preferential activation
ratio of TrA in tabletop, seated, standing, and walking positions were assessed
by the same examiner during 2 ultrasound imaging sessions 24-72 hours apart.
Statistical analysis included determination of intraclass correlation
coefficients (ICCs) using analysis of variance for each muscle and position
between sessions. RESULTS: Excellent reliability was found in TrA AR between
sessions for healthy participants in the tabletop position (ICC3,k = 0.903), and
acceptable to excellent reliability was found in seated (ICC3,k = 0.613),
standing (ICC3,k = 0.553), and walking (ICC3,k = 0.737) positions. LM AR was fair
in the tabletop position for these participants (ICC3,k = 0.264). The
preferential activation ratio for healthy participants was substantially reliable
in tabletop and seated positions (ICC3,k = 0.668, 0.684) and showed fair
reliability for walking (ICC3,k = 0.455). CONCLUSIONS: Ultrasound imaging is a
reliable method of measuring muscle thickness across multiple positions in
healthy persons. This measure may be used to compare abdominal muscle thickness
across populations or after interventions. LM AR was only found to be reliable in
the tabletop position.
PMID- 26428486
TI - A Phase II Trial of Fludarabine/Melphalan 100 Conditioning Therapy Followed by
Allogeneic Hematopoietic Cell Transplantation for Patients With Lymphoma.
AB - BACKGROUND: Conditioning therapy with fludarabine and melphalan 140 mg/m(2) has
been widely used before allogeneic hematopoietic cell transplantation (HCT) for
lymphoma. A lower dose of melphalan might result in lower mortality and morbidity
without compromising engraftment. PATIENTS AND METHODS: In our phase II trial, we
investigated a conditioning regimen of fludarabine (30 mg/m(2)/day for 5 days on
days -6 to -2) and melphalan (100 mg/m(2) on day -2). Antithymocyte globulin was
added to fludarabine and melphalan for unrelated or mismatched familial donor
HCT. The present study included 26 patients with lymphoma (B-cell in 10, T-cell
in 11, and natural killer/T-cell lymphoma in 2). RESULTS: An objective tumor
response after HCT was observed in 18 patients (75.0%; complete in 14 and partial
in 4). Acute and chronic graft-versus-host disease (GVHD) occurred in 23.1% and
55.0% of the assessable patients, respectively. The 5-year overall survival,
nonrelapse mortality, progression-free survival, and event-free survival rate was
40.4%, 21.6%, 39.2%, and 30.8%, respectively. Donor lymphocyte infusions were
given to 3 patients who had developed a relapse or progression after HCT, and 2
of whom had a showed partial response. Patients with severe chronic GVHD had
greater overall survival than those with no, mild, or moderate chronic GVHD.
CONCLUSION: Conditioning therapy with a lower dose of melphalan, combined with
fludarabine, appears to be promising in allogeneic HCT for lymphoma. The
Clinicaltrials.gov identification number for the present study is NCT00772811.
PMID- 26428487
TI - Images of the human placenta.
PMID- 26428488
TI - Functional imaging of the human placenta with magnetic resonance.
AB - Abnormal placentation is responsible for most failures in pregnancy; however, an
understanding of placental functions remains largely concealed from noninvasive,
in vivo investigations. Magnetic resonance imaging (MRI) is safe in pregnancy for
magnetic fields of up to 3 Tesla and is being used increasingly to improve the
accuracy of prenatal imaging. Functional MRI (fMRI) of the placenta has not yet
been validated in a clinical setting, and most data are derived from animal
studies. FMRI could be used to further explore placental functions that are
related to vascularization, oxygenation, and metabolism in human pregnancies by
the use of various enhancement processes. Dynamic contrast-enhanced MRI is best
able to quantify placental perfusion, permeability, and blood volume fractions.
However, the transplacental passage of Gadolinium-based contrast agents
represents a significant safety concern for this procedure in humans. There are
alternative contrast agents that may be safer in pregnancy or that do not cross
the placenta. Arterial spin labeling MRI relies on magnetically labeled water to
quantify the blood flows within the placenta. A disadvantage of this technique is
a poorer signal-to-noise ratio. Based on arterial spin labeling, placental
perfusion in normal pregnancy is 176 +/- 91 mL * min(-1) * 100 g(-1) and
decreases in cases with intrauterine growth restriction. Blood oxygen level
dependent and oxygen-enhanced MRIs do not assess perfusion but measure the
response of the placenta to changes in oxygen levels with the use of hemoglobin
as an endogenous contrast agent. Diffusion-weighted imaging and intravoxel
incoherent motion MRI do not require exogenous contrast agents, instead they use
the movement of water molecules within tissues. The apparent diffusion
coefficient and perfusion fraction are significantly lower in placentas of growth
restricted fetuses when compared with normal pregnancies. Magnetic resonance
spectroscopy has the ability to extract information regarding metabolites from
the placenta noninvasively and in vivo. There are marked differences in all 3
metabolites N-acetyl aspartate/choline levels, inositol/choline ratio between
small, and adequately grown fetuses. Current research is focused on the ability
of each fMRI technique to make a timely diagnosis of abnormal placentation that
would allow for appropriate planning of follow-up examinations and optimal
scheduling of delivery. These research programs will benefit from the use of well
defined sequences, standardized imaging protocols, and robust computational
methods.
PMID- 26428490
TI - How the placenta affects your life, from womb to tomb.
PMID- 26428489
TI - Why is placentation abnormal in preeclampsia?
AB - The causes of preeclampsia remain one of the great medical mysteries of our time.
This syndrome is thought to occur in 2 stages with abnormal placentation leading
to a maternal inflammatory response. Specific regions of the placenta have
distinct pathologic features. During normal pregnancy, cytotrophoblasts emigrate
from the chorionic villi and invade the uterus, reaching the inner third of the
myometrium. This unusual process is made even more exceptional by the fact that
the placental cells are hemiallogeneic, coexpressing maternal and paternal
genomes. Within the uterine wall, cytotrophoblasts deeply invade the spiral
arteries. Cytotrophoblasts migrate up these vessels and replace, in a retrograde
fashion, the maternal endothelial lining. They also insert themselves among the
smooth muscle cells that form the tunica media. As a result, the spiral arteries
attain the physiologic properties that are required to perfuse the placenta
adequately. In comparison, invasion of the venous side of the uterine circulation
is minimal, sufficient to enable venous return. In preeclampsia, cytotrophoblast
invasion of the interstitial uterine compartment is frequently shallow, although
not consistently so. In many locations, spiral artery invasion is incomplete.
There are many fewer endovascular cytotrophoblasts, and some vessels retain
portions of their endothelial lining with relatively intact muscular coats,
although others are not modified. Work from our group showed that these defects
mirror deficits in the differentiation program that enables cytotrophoblast
invasion of the uterine wall. During normal pregnancy, invasion is accompanied by
the down-regulation of epithelial-like molecules that are indicative of their
ectodermal origin and up-regulation of numerous receptors and ligands that
typically are expressed by endothelial or vascular smooth muscle cells. For
example, the expression of epithelial-cadherin (the cell-cell adhesion molecule
that many ectodermal derivatives use to adhere to one another) becomes nearly
undetectable, replaced by vascular-endothelial cadherin, which serves the same
purpose in blood vessels. Invading cytotrophoblasts also modulate vascular
endothelial growth factor ligands and receptors, at some point in the
differentiation process expressing every (mammalian) family member. Molecules in
this family play crucial roles in vascular and trophoblast biology, including the
prevention of apoptosis. In preeclampsia, this process of vascular mimicry is
incomplete, which we theorize hinders the cells interactions with spiral
arterioles. What causes these aberrations? Given what is known from animal models
and human risk factors, reduced placental perfusion and/or certain disease states
(metabolic, immune and cardiovascular) lie upstream. Recent evidence suggests the
surprising conclusion that isolation and culture of cytotrophoblasts from the
placentas of pregnancies complicated by preeclampsia enables normalization of
their gene expression. The affected molecules include SEMA3B, which down
regulates vascular endothelial growth factor signaling through the PI3K/AKT and
GSK3 pathways. Thus, some aspects of the aberrant differentiation of
cytotrophoblasts within the uterine wall that is observed in situ may be
reversible. The next challenge is asking what the instigating causes are. There
is added urgency to finding the answers, because these pathways could be valuable
therapeutic targets for reversing abnormal placental function in patients.
PMID- 26428492
TI - Trophoblast-microbiome interaction: a new paradigm on immune regulation.
AB - The immunologic paradigm of pregnancy led to the conceptualization of pregnancy
as an organ transplant that requires, for its success, suppression of the
maternal immune system. Growing scientific evidence suggests that in many ways
the placenta functions as a tumor rather than a transplant and the immune
regulation of the maternal-fetal interface is the result of the coordinated
interaction between all its cellular components, including bacteria. Examining
the role of microbiota in reproduction is in its infancy, but there is growing
literature that supports its relevance. We discuss a potential normal function of
bacteria in the establishment of immune tolerance and compelling evidence that a
viral infection might be the underlying cause of perturbation of homeostasis.
There is compelling evidence that many infectious diseases of human beings are
caused by >1 microorganism and are defined as polymicrobial infections. We
propose that pregnancy complications, such as preterm birth, are the result of
polymicrobial infections. We examine the potential cellular and molecular
mechanisms by which a viral infection of the placenta might disrupt the normal
interaction between the cellular component of the implantation site and bacteria.
As we better understand the normal homeostasis among the maternal immune system,
placenta, and commensal, we will be able to elucidate pathogenic conditions and
design better approaches to treat pregnancy complications associated with
infection.
PMID- 26428491
TI - Role of the fetoplacental endothelium in fetal growth restriction with abnormal
umbilical artery Doppler velocimetry.
AB - Growth-restricted fetuses with absent or reversed end-diastolic velocities in the
umbilical artery are at substantially increased risk for adverse perinatal and
long-term outcome, even in comparison to growth-restricted fetuses with preserved
end-diastolic velocities. Translational studies show that this Doppler
velocimetry correlates with fetoplacental blood flow, with absent or reversed end
diastolic velocities signifying abnormally elevated resistance within the
placental vasculature. The fetoplacental vasculature is unique in that it is not
subject to autonomic regulation, unlike other vascular beds. Instead, humoral
mediators, many of which are synthesized by local endothelial cells, regulate
placental vascular resistance. Existing data demonstrate that in growth
restricted pregnancies complicated by absent or reversed umbilical artery end
diastolic velocities, an imbalance in production of these vasoactive substances
occurs, favoring vasoconstriction. Morphologically, placentas from these
pregnancies also demonstrate impaired angiogenesis, whereby vessels within the
terminal villi are sparsely branched, abnormally thin, and elongated. This
structural deviation from normal placental angiogenesis restricts blood flow and
further contributes to elevated fetoplacental vascular resistance. Although
considerable work has been done in the field of fetoplacental vascular
development and function, much remains unknown about the mechanisms underlying
impaired development and function of the human fetoplacental vasculature,
especially in the context of severe fetal growth restriction with absent or
reversed umbilical artery end-diastolic velocities. Fetoplacental endothelial
cells are key regulators of angiogenesis and vasomotor tone. A thorough
understanding of their role in placental vascular biology carries the significant
potential of discovering clinically relevant and innovative approaches to
prevention and treatment of fetal growth restriction with compromised umbilical
artery end-diastolic velocities.
PMID- 26428493
TI - Placental transcriptome in development and pathology: expression, function, and
methods of analysis.
AB - The placenta is the essential organ of mammalian pregnancy and errors in its
development and function are associated with a wide range of human pathologies of
pregnancy. Genome sequencing has led to methods for investigation of the
transcriptome (all expressed RNA species) using microarrays and next-generation
sequencing, and implementation of these techniques has identified many novel
species of RNA including: micro-RNA, long noncoding RNA, and circular RNA. These
species can physically interact with both each other and regulatory proteins to
modify gene expression and messenger RNA to protein translation. Transcriptome
analysis is actively used to investigate placental development and dysfunction in
pathologies ranging from preeclampsia and fetal growth restriction to preterm
labor. Genome-wide gene expression analysis is also being applied to identify
prognostic and diagnostic biomarkers of these disorders. In this comprehensive
review we summarize transcriptome biology, methods of isolation and analysis,
application to placental development and pathology, and use in diagnostic
analysis in maternal blood. Key information for analysis methods is organized
into quick reference tables where current analysis techniques and tools are cited
and compared. We have created this review as a practical guide and starting
reference for those interested in beginning an investigation into the
transcriptome of the placenta.
PMID- 26428494
TI - The placenta is the center of the chronic disease universe.
PMID- 26428495
TI - Genomic imprinting in the human placenta.
AB - With the launch of the National Institute of Child Health and Human
Development/National Institutes of Health Human Placenta Project, the
anticipation is that this often-overlooked organ will be the subject of much
intense research. Compared with somatic tissues, the cells of the placenta have a
unique epigenetic profile that dictates its transcription patterns, which when
disturbed may be associated with adverse pregnancy outcomes. One major class of
genes that is dependent on strict epigenetic regulation in the placenta is
subject to genomic imprinting, the parent-of-origin-dependent monoallelic gene
expression. This review discusses the differences in allelic expression and
epigenetic profiles of imprinted genes that are identified between different
species, which reflect the continuous evolutionary adaption of this form of
epigenetic regulation. These observations divulge that placenta-specific
imprinted gene that is reliant on repressive histone signatures in mice are
unlikely to be imprinted in humans, whereas intense methylation profiling in
humans has uncovered numerous maternally methylated regions that are restricted
to the placenta that are not conserved in mice. Imprinting has been proposed to
be a mechanism that regulates parental resource allocation and ultimately can
influence fetal growth, with the placenta being the key in this process.
Furthermore, I discuss the developmental dynamics of both classic and transient
placenta-specific imprinting and examine the evidence for an involvement of these
genes in intrauterine growth restriction and placenta-associated complications.
Finally, I focus on examples of genes that are regulated aberrantly in
complicated pregnancies, emphasizing their application as pregnancy-related
disease biomarkers to aid the diagnosis of at-risk pregnancies early in
gestation.
PMID- 26428497
TI - Placental exosomes in normal and complicated pregnancy.
AB - While there is considerable contemporary interest in elucidating the role of
placenta-derived extracellular vesicles in normal and complicated pregnancies and
their utility as biomarkers and therapeutic interventions, progress in the field
is hindered by a lack of standardized extracellular vesicle taxonomy and
isolation protocols. The term "extracellular vesicle" is nonspecific and refers
to all membrane-bound vesicles from nanometer to micrometer diameters and of
different biogenic origins. To meaningfully ascribe biological function and/or
diagnostic and therapeutic utility to extracellular vesicles, and in particular
exosomes, greater specificity and vesicle characterization is required. The
current literature relating to exosome biology must be interpreted in this
context. Exosomes are a subtype of extracellular vesicle that are specifically
defined by an endosomal biogenesis and particle size (40-120 nm) and density
(1.13-1.19 g/mL(-1)). Exosomes are specifically package with signaling molecules
(including protein, messenger RNA, microRNA, and noncoding RNA) and are released
by exocytosis into biofluid compartments. Exosomes regulate the activity of both
proximal and distal target cells, including translational activity, angiogenesis,
proliferation, metabolism, and apoptosis. As such, exosomal signaling represents
an integral pathway mediating intercellular communication. During pregnancy, the
placenta releases exosomes into the maternal circulation from as early as 6 weeks
of gestation. Release is regulated by factors that include both oxygen tension
and glucose concentration and correlates with placental mass and perfusion. The
concentration of placenta-derived exosomes in maternal plasma increases
progressively during gestation. Exosomes isolated from maternal plasma are
bioactive in vitro and are incorporated into target cells by endocytosis. While
the functional significance of placental exosomes in pregnancy remains to be
fully elucidated, available data support a role in normal placental development
and maternal immunotolerance. Similarly, the role of exosomes in the etiology and
progression of complications of pregnancy remains in a formative stage. Changes
in the release of placenta- and nonplacenta-derived exosomes, their concentration
in maternal plasma, composition, and bioactivity have been reported in
association with pregnancies complicated by gestational diabetes and
preeclampsia. The data, however, are confounded by the use of different isolation
methodologies and vesicle subpopulations. The application of specific and well
characterized isolation methodologies is requisite to resolving the precise role
of exosomes in complications of pregnancies and their ultimate clinical utility.
PMID- 26428498
TI - Epigenetic regulation of human placental function and pregnancy outcome:
considerations for causal inference.
AB - Epigenetic mechanisms, often defined as regulating gene activity independently of
underlying DNA sequence, are crucial for healthy development. The sum total of
epigenetic marks within a cell or tissue (the epigenome) is sensitive to
environmental influence, and disruption of the epigenome in utero has been
associated with adverse pregnancy outcomes. Not surprisingly, given its
multifaceted functions and important role in regulating pregnancy outcome, the
placenta shows unique epigenetic features. Interestingly however, many of these
are only otherwise seen in human malignancy (the pseudomalignant placental
epigenome). Epigenetic variation in the placenta is now emerging as a candidate
mediator of environmental influence on placental functioning and a key regulator
of pregnancy outcome. However, replication of findings is generally lacking, most
likely due to small sample sizes and a lack of standardization of analytical
approaches. Defining DNA methylation "signatures" in the placenta associated with
maternal and fetal outcomes offers tremendous potential to improve pregnancy
outcomes, but care must be taken in interpretation of findings. Future placental
epigenetic research would do well to address the issues present in epigenetic
epidemiology more generally, including careful consideration of sample size,
potentially confounding factors, issues of tissue heterogeneity, reverse
causation, and the role of genetics in modulating epigenetic profile. The
importance of animal or in vitro models in establishing a functional role of
epigenetic variation identified in human beings, which is key to establishing
causation, should not be underestimated.
PMID- 26428496
TI - MicroRNAs in placental health and disease.
AB - MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that are
encoded by the genomes of most organisms. They regulate gene expression through
posttranscriptional mechanisms to attenuate protein output in various genetic
networks. The discovery of miRNAs has transformed our understanding of gene
regulation and sparked intense efforts intended to harness their potential as
diagnostic markers and therapeutic tools. Over the last decade, a flurry of
studies has shed light on placental miRNAs but has also raised many questions
regarding the scope of their biologic action. Moreover, the recognition that
miRNAs of placental origin are released continually in the maternal circulation
throughout pregnancy suggested that circulating miRNAs might serve as biomarkers
for placental function during pregnancy. Although this generated much enthusiasm,
recently recognized challenges have delayed the application of miRNA-based
biomarkers and therapeutics in clinical practice. In this review, we summarize
key findings in the field and discuss current knowledge related to miRNAs in the
context of placental biology.
PMID- 26428499
TI - Noninvasive nucleic acid-based approaches to monitor placental health and predict
pregnancy-related complications.
AB - During pregnancy, the placenta releases a variety of nucleic acids (including
deoxyribonucleic acid, messenger ribonucleic acid, or microribonucleic acids)
either as a result of cell turnover or as an active messaging system between the
placenta and cells in the maternal body. The profile of released nucleic acids
changes with the gestational age and has been associated with maternal and fetal
parameters. It also can directly reflect pathological changes in the placenta.
Nucleic acids may therefore provide a rich source of novel biomarkers for the
prediction of pregnancy complications. However, their utility in the clinical
setting depends, first, on overcoming some technical considerations in their
quantification, and, second, on developing a better understanding of the factors
that influence their function and abundance.
PMID- 26428500
TI - Classification of placental lesions.
AB - Placental pathology can be useful in a variety of ways including immediate
diagnosis of important conditions affecting the mother or infant, identifying
conditions that are likely to recur in subsequent pregnancies, separating
clinical syndromes into distinct pathological phenotypes for further
investigation, and uncovering the underlying cause of unexpected adverse
outcomes. Classification of placental lesions has evolved from being a purely
descriptive exercise through a stage in which the major pathophysiological
processes such as disorders of maternal implantation and the amniotic fluid
infection syndrome were first described to a recently proposed comprehensive
classification system that includes all of the major maternal and fetal vascular
and infectious and idiopathic/immune inflammatory processes (Amsterdam Placental
Workshop Group). Implementation of this unified system with reproducible grading
and staging should help establish evidence-based recommendations for placental
submission and facilitate progress in studying the pathogenesis, diagnosis, and
treatment of obstetric disorders with an underlying placental etiology.
PMID- 26428502
TI - The human placenta project: it's time for real time.
PMID- 26428504
TI - What is the placenta?
AB - Discarded at birth, the placenta is a highly complex and fascinating organ.
During the course of a pregnancy, it acts as the lungs, gut, kidneys, and liver
of the fetus. The placenta also has major endocrine actions that modulate
maternal physiology and metabolism and provides a safe and protective milieu in
which the fetus can develop. The human placenta undergoes dramatic
transformations in form and function between the first trimester, when
organogenesis occurs, and the remainder of pregnancy that reflect evolutionary
responses to changing oxygen concentrations in the earth's atmosphere. Recent
research indicates a more interactive dialogue between the placenta and the
maternal tissues than previously recognized. The endometrial glands provide
histotrophic support during the first weeks of pregnancy, and the placenta
appears able to stimulate its own development by up-regulating gland activity in
response to endocrine signals. Extravillous trophoblast cells migrate from the
placenta into the uterine wall, in which they interact with cells of the maternal
innate immune system. These interactions have a physiological, rather than a
classical immunological, outcome and most probably mediate remodeling of the
uterine spiral arteries that supply the placenta. Furthermore, deportation of
aggregates of transcriptionally active trophoblast nuclei, and the release of
exosomes carrying microribonucleic acids challenge our perceptions of fetal
maternal signaling and where the placental interface actually lies. Here we
reconsider definitions of the placenta in the light of these recent advances.
PMID- 26428505
TI - Using ultrasound in the clinical management of placental implantation
abnormalities.
AB - Placental implantation abnormalities, including placenta previa, placenta
accreta, vasa previa, and velamentous cord insertion, can have catastrophic
consequences for both mother and fetus, especially as pregnancy progresses to
term. In these situations, current recommendations for management usually call
for an indicated preterm delivery even in asymptomatic patients. However, the
recommended gestational age(s) for delivery in asymptomatic patients are
empirically determined without consideration of the recent literature regarding
the usefulness of specific ultrasound findings to help individualize management.
The purpose of this article is to propose literature-supported guidelines to the
current opinion-based management of asymptomatic patients with placental
implantation abnormalities based on relevant and specific ultrasound findings
such as cervical length, distance between the internal cervical os and placenta,
and placental edge thickness.
PMID- 26428506
TI - Placental implantation abnormalities and risk of preterm delivery: a systematic
review and metaanalysis.
AB - We sought to evaluate the extent of the association between placental
implantation abnormalities (PIA) and preterm delivery in singleton gestations. We
conducted a systematic review of English-language articles published from 1980
onward using PubMed, MEDLINE, EMBASE, CINAHL, LILACS, and Google Scholar, and by
identifying studies cited in the references of published articles. Search terms
were PIA defined as >= 1 of the following: placenta previa, placenta accreta,
vasa previa, and velamentous cord insertion. Observational and experimental
studies were included for review if data were available regarding any of the
aforementioned PIA and regarding gestational age at delivery or preterm delivery.
Case reports and case series were excluded. Studies were reviewed and data
extracted. The primary outcome was gestational age at delivery or preterm
delivery <37 weeks' gestation. Secondary outcomes included birthweight, 1- and 5
minute Apgar scores, neonatal intensive care unit (NICU) admission, neonatal and
perinatal death, and small for gestational age. Of the 1421 studies identified,
79 met the defined criteria; 56 studies were descriptive and 23 were comparative.
Based on the descriptive studies, the preterm delivery rates for low
lying/marginal placenta, placenta previa, placenta accreta, vasa previa, and
velamentous cord insertion were 26.9%, 43.5%, 57.7%, 81.9%, and 37.5%,
respectively. Based on the comparative studies using controls, there was
decreased pregnancy duration for every PIA; more specifically, there was an
increased risk for preterm delivery in patients with placenta previa (risk ratio
[RR], 5.32; 95% confidence interval [CI], 4.39-6.45), vasa previa (RR, 3.36; 95%
CI, 2.76-4.09), and velamentous cord insertion (RR, 1.95; 95% CI, 1.67-2.28).
Risks of NICU admissions (RR, 4.09; 95% CI, 2.80-5.97), neonatal death (RR, 5.44;
95% CI, 3.03-9.78), and perinatal death (RR, 3.01; 95% CI, 1.41-6.43) were higher
with placenta previa. Perinatal risks were also higher in patients with vasa
previa (perinatal death rate RR, 4.52; 95% CI, 2.77-7.39) and velamentous cord
insertion (NICU admissions [RR, 1.76; 95% CI, 1.68-1.84], small for gestational
age [RR, 1.69; 95% CI, 1.56-1.82], and perinatal death [RR, 2.15; 95% CI, 1.84
2.52]). In singleton gestations, there is a strong association between PIA and
preterm delivery resulting in significant perinatal morbidity and mortality.
PMID- 26428507
TI - Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity.
AB - The maternal syndrome of preeclampsia is mediated by dysfunctional
syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion,
its signaling to the mother changes, as part of a highly coordinated stress
response. The STB signals are both proinflammatory and dysangiogenic such that
the preeclamptic mother has a stronger vascular inflammatory response than
normal, with an antiangiogenic bias. Angiogenic factors have limitations as
preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia
at term. However, if they are recognized as markers of STB stress, their
physiological changes at term demonstrate that STB stress develops in all
pregnancies. The biomarkers reveal that the duration of pregnancies is restricted
by placental capacity, such that there is increasing placental dysfunction, at
and beyond term. This capacity includes limitations imposed by the size of the
uterus, the capacity of the uteroplacental circulation and, possibly, the supply
of villous progenitor trophoblast cells. Limited placental capacity explains the
increasing risks of postmaturity, including preeclampsia. Early-onset
preeclampsia is predictable because STB stress and changes in its biomarkers are
intrinsic to poor placentation, an early pregnancy pathology. Prediction of
preeclampsia at term is not good because there is no early STB pathology.
Moreover, biomarkers cannot accurately diagnose term preeclampsia against a
background of universal STB dysfunction, which may or may not be clinically
revealed before spontaneous or induced delivery. In this sense, postterm
pregnancy is, at best, a pseudonormal state. However, the markers may prove
useful in screening for women with more severe problems of postmaturity.
PMID- 26428503
TI - Chronic inflammation of the placenta: definition, classification, pathogenesis,
and clinical significance.
AB - Chronic inflammatory lesions of the placenta are characterized by the
infiltration of the organ by lymphocytes, plasma cells, and/or macrophages and
may result from infections (viral, bacterial, parasitic) or be of immune origin
(maternal anti-fetal rejection). The 3 major lesions are villitis (when the
inflammatory process affects the villous tree), chronic chorioamnionitis (which
affects the chorioamniotic membranes), and chronic deciduitis (which involves the
decidua basalis). Maternal cellular infiltration is a common feature of the
lesions. Villitis of unknown etiology (VUE) is a destructive villous inflammatory
lesion that is characterized by the infiltration of maternal T cells (CD8+
cytotoxic T cells) into chorionic villi. Migration of maternal T cells into the
villi is driven by the production of T-cell chemokines in the affected villi.
Activation of macrophages in the villi has been implicated in the destruction of
the villous architecture. VUE has been reported in association with preterm and
term fetal growth restriction, preeclampsia, fetal death, and preterm labor.
Infants whose placentas have VUE are at risk for death and abnormal
neurodevelopmental outcome at the age of 2 years. Chronic chorioamnionitis is the
most common lesion in late spontaneous preterm birth and is characterized by the
infiltration of maternal CD8+ T cells into the chorioamniotic membranes. These
cytotoxic T cells can induce trophoblast apoptosis and damage the fetal
membranes. The lesion frequently is accompanied by VUE. Chronic deciduitis
consists of the presence of lymphocytes or plasma cells in the basal plate of the
placenta. This lesion is more common in pregnancies that result from egg donation
and has been reported in a subset of patients with premature labor. Chronic
placental inflammatory lesions can be due to maternal anti-fetal rejection, a
process associated with the development of a novel form of fetal systemic
inflammatory response. The syndrome is characterized by an elevation of the fetal
plasma T-cell chemokine. The evidence that maternal anti-fetal rejection
underlies the pathogenesis of many chronic inflammatory lesions of the placenta
is reviewed. This article includes figures and histologic examples of all chronic
inflammatory lesions of the placenta.
PMID- 26428501
TI - Acute chorioamnionitis and funisitis: definition, pathologic features, and
clinical significance.
AB - Acute inflammatory lesions of the placenta consist of diffuse infiltration of
neutrophils at different sites in the organ. These lesions include acute
chorioamnionitis, funisitis, and chorionic vasculitis and represent a host
response (maternal or fetal) to a chemotactic gradient in the amniotic cavity.
While acute chorioamnionitis is evidence of a maternal host response, funisitis
and chorionic vasculitis represent fetal inflammatory responses. Intraamniotic
infection generally has been considered to be the cause of acute chorioamnionitis
and funisitis; however, recent evidence indicates that "sterile" intraamniotic
inflammation, which occurs in the absence of demonstrable microorganisms induced
by "danger signals," is frequently associated with these lesions. In the context
of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte
chemotactic protein) establish a gradient that favors the migration of
neutrophils from the maternal or fetal circulation into the chorioamniotic
membranes or umbilical cord, respectively. Danger signals that are released
during the course of cellular stress or cell death can also induce the release of
neutrophil chemokines. The prevalence of chorioamnionitis is a function of
gestational age at birth, and present in 3-5% of term placentas and in 94% of
placentas delivered at 21-24 weeks of gestation. The frequency is higher in
patients with spontaneous labor, preterm labor, clinical chorioamnionitis
(preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are
the hallmarks of the fetal inflammatory response syndrome, a condition
characterized by an elevation in the fetal plasma concentration of interleukin-6,
and associated with the impending onset of preterm labor, a higher rate of
neonatal morbidity (after adjustment for gestational age), and multiorgan fetal
involvement. This syndrome is the counterpart of the systemic inflammatory
response syndrome in adults: a risk factor for short- and long-term complications
(ie, sterile inflammation in fetuses, neonatal sepsis, bronchopulmonary
dysplasia, periventricular leukomalacia, and cerebral palsy). This article
reviews the definition, pathogenesis, grading and staging, and clinical
significance of the most common lesions in placental disease. Illustrations of
the lesions and diagrams of the mechanisms of disease are provided.
PMID- 26428508
TI - Anomalies of the placenta and umbilical cord in twin gestations.
AB - The frequency of twin gestations has increased over the last few decades, mainly
due to maternal age at childbearing, and the use of assisted reproductive
technologies. Twins are at higher risk of aneuploidy, structural anomalies, and
placental abnormalities. Some of the placental and umbilical cord abnormalities
found in twin gestations are nonspecific and can be found in singleton gestations
(ie, placenta previa, placental abruption, single umbilical artery, velamentous
cord insertion, vasa previa, etc). However, other anomalies are unique to twin
gestations, and are mainly associated with monochorionic twins-these include
intraplacental anastomosis and cord entanglement. Most of these conditions can be
diagnosed with ultrasound. An accurate and early diagnosis is important in the
management of twin gestations. Determination of chorionicity, amnionicity, and
the identification of placental anomalies are key issues for the adequate
management of twin pregnancies. Pathologic placental examination after delivery
can help in assessing the presence of placental and umbilical cord abnormalities,
as well as providing information about chorionicity and gaining insight into the
potential mechanisms of disease affecting twin gestations.
PMID- 26428509
TI - Emergency percutaneous, bicaval double-lumen, ECMO cannulation in neonates and
infants: insights from three consecutive cases.
AB - BACKGROUND: Veno-venous extracorporeal membrane oxygenation (ECMO) is probably
the preferable configuration to assist children with respiratory failure who do
not respond to maximized conventional therapies. The single-vessel, double-lumen
approach through the internal jugular vein is extremely advantageous, especially
in infants, where femoral access presents limitations related to the small
dimensions of the veins. In case of emergencies, ECMO might need to be started at
the bedside, without the availability of fluoroscopic guidance. To our knowledge,
a completely percutaneous approach has not been reported before in children
younger than 1 year and weighing less than 5 kg. METHODS: We describe 3 cases of
emergency bedside, percutaneous, bicaval double-lumen cannulation under real-time
transthoracic ultrasound control in 2 neonates and 1 infant. RESULTS: In our
experience, this approach proved to be safe, effective and time saving, while
minimizing bleeding from the cannula insertion site. Cannulation times, from
decision making to the beginning of ECMO flow, were 30, 28, 25 minutes
respectively, from patient 1 to 3. We do not report any cannula-related injury to
vessels and heart structures. CONCLUSIONS: Our preliminary data suggest that,
with the described precautions, percutaneous, echo-guided, bicaval double-lumen
cannulation in neonates and infants could be effective and free from major
complications. Further evaluation should be warranted in the neonatal population.
PMID- 26428510
TI - A Comparison of Techniques for Optimal Performance of Bronchoalveolar Lavage.
AB - BACKGROUND: Bronchoalveolar lavage (BAL) is a commonly used diagnostic and
research tool. Currently, there is limited evidence regarding standardizing this
technique. The type of suction method and number of aliquots used as well as the
anatomic lung segment sampled are not standardized nor well studied. Our primary
aim was to compare the quantity and quality of BAL specimens using 2 suction
methods, hand-held syringe versus wall suction. Our secondary aim was to assess
which anatomic lung segment yields the greatest BAL results and how many aliquots
are required. METHODS: A prospective clinical study was performed in patients
undergoing bronchoscopies using hand-held syringe or wall suction. On the basis
of radiologic findings, 100 mL (with 4 aliquots) of normal saline was instilled
and the percentage volume return calculated. RESULTS: Sixy-six patients were
enrolled. Thirty-three patients received hand-held syringe and 33 using wall
suction. There was no significant difference in the percentage volume returned,
or the adequacy of fluid between these suction methods. When comparing volumes of
return from different lobes, greater returns were demonstrated from the right
middle lobe (P=0.002). In addition, with each sequential aliquot instilled, the
return of fluid was increased significantly (P<0.001). CONCLUSIONS: No
significant difference was observed between hand-held syringe and wall suction in
terms of volumes returned and microbiological or diagnostic yield. Performance of
BAL in the right middle lobe is associated with increased return and should be
preferentially used when performing a nontargeted BAL in patients with diffuse
computed tomography chest changes.
PMID- 26428511
TI - Wingless mediated apoptosis: How cone cells direct the death of peripheral
ommatidia in the developing Drosophila eye.
AB - Morphogen gradients play pervasive roles in development, and understanding how
they are established and decoded is a major goal of contemporary developmental
biology. Here we examine how a Wingless (Wg) morphogen gradient patterns the
peripheral specialization of the fly eye. The outermost specialization is the
pigment rim; a thick band of pigment cells that circumscribes the eye and
optically insulates the sides of the retina. It results from the coalescence of
pigment cells that survive the death of the outermost row of developing
ommatidia. We investigate here how the Wg target genes expressed in the moribund
ommatidia direct the intercellular signaling, the morphogenetic movements, and
ultimately the ommatidial death. A salient feature of this process is the
secondary expression of the Wg morphogen elicited in the ommatidia by the primary
Wg signal. We find that neither the primary nor secondary sources of Wg alone are
able to promote ommatidial death, but together they suffice to drive the
apoptosis. This represents an unusual gradient read-out process in which a
morphogen induces its own expression in its target cells to generate a
concentration spike required to push the local cellular responses to the next
threshold response.
PMID- 26428512
TI - Introduction to the special issue: Data Part 2: Experimental Data.
PMID- 26428513
TI - TAS-102, a novel antitumor agent: a review of the mechanism of action.
AB - Inhibition of nucleoside metabolism is an important principle in cancer therapy
as evidenced by the role of fluoropyrimidines, such as 5-fluorouracil (5-FU), and
antifolates in the treatment of many cancers. TAS-102 is an oral combination
therapy consisting of trifluridine (FTD), a thymidine-based nucleoside analog,
plus tipiracil hydrochloride (TPI), a novel thymidine phosphorylase inhibitor
that improves the bioavailability of FTD. TAS-102 has demonstrated efficacy in 5
FU-refractory patients based on a different mechanism of action and has been
approved for the treatment of metastatic colorectal cancer in Japan. This review
describes the mechanism of action of TAS-102, highlighting key differences
between TAS-102 and 5-FU-based therapies. While both FTD and 5-FU inhibit
thymidylate synthase (TS), a central enzyme in DNA synthesis, sufficient TS
inhibition by FTD requires continuous infusion; therefore, it is not considered a
clinically relevant mechanism with oral dosing. Instead, the primary cytotoxic
mechanism with twice-daily oral dosing, the schedule used in TAS-102 clinical
development, is DNA incorporation. FTD incorporation into DNA induces DNA
dysfunction, including DNA strand breaks. Uracil-based analogs such as 5-FU may
also be incorporated into DNA; however, they are immediately cleaved off by
uracil-DNA glycosylases, reducing their ability to damage DNA. Moreover, the TPI
component may enhance the durability of response to FTD. With its distinct
mechanism of action and metabolism, TAS-102 is a promising treatment option for
patients resistant to or intolerant of 5-FU-based fluoropyrimidines.
PMID- 26428515
TI - On the Plausibility of Pseudosugar Formation in Cometary Ices and Oxygen-rich
Tholins.
AB - We revisit herein the formation and structure of dihydroxy dioxanes, which can be
obtained from prebiotically available precursors and can be regarded as primeval
sugar surrogates. Previous studies dealing with the heterogeneous composition of
interstellar bodies point to the existence of significant amounts of small
polyalcohols along with oxygen-containing oligomers. Even though such derivatives
did not give rise to nucleosides and oligonucleotides, nor they were incorporated
into subsequent metabolic routes, molecular chimeras based on sugar-like species
could be opportunistic scaffolds in pre-evolutionary scenarios. We could figure
out that pseudosugars, assembled by hemiacetalic bonds from available precursors
in both interstellar and terrestrial scenarios, were presumably more abundant
than thought. Moreover, these species share some key features with naturally
occurring sugar rings, such as anomeric preferences, coordinating ability, and
the prevalent occurrence of racemic compounds.
PMID- 26428516
TI - Interventional ASD II closure in the presence of an abnormally localized left
main coronary artery.
PMID- 26428514
TI - Cell-free mitochondrial DNA in CSF is associated with early viral rebound,
inflammation, and severity of neurocognitive deficits in HIV infection.
AB - Cell-free mitochondiral DNA (mtDNA) is an immunogenic molecule associated with
many inflammatory conditions. We evaluated the relationship between cell-free
mtDNA in cerebrospinal fluid (CSF) and neurocognitive performance and
inflammation during HIV infection. In a cross-sectional analysis, we evaluated
the association of mtDNA levels with clinical assessments, inflammatory markers,
and neurocognitive performance in 28 HIV-infected individuals. In CSF, we
measured mtDNA levels by droplet digital PCR, and soluble CD14 and CD163,
neurofilament light, and neopterin by ELISA. In blood and CSF, we measured
soluble IP-10, MCP-1, TNF-alpha, and IL-6 by ELISA, and intracellular expression
of IL-2, IFN-gamma, and TNF-alpha in CD4(+) and CD8(+) T cells by flow cytometry.
We also evaluated the relationship between CSF pleocytosis and mtDNA
longitudinally in another set of five individuals participating in an
antiretroviral treatment (ART) interruption study. Cell-free CSF mtDNA levels
strongly correlated with neurocognitive performance among individuals with
neurocognitive impairment (NCI) (r = 0.77, p = 0.001). CSF mtDNA also correlated
with levels of IP-10 in CSF (r = 0.70, p = 0.007) and MCP-1 in blood plasma (r =
0.66, p = 0.01) in individuals with NCI. There were no significant associations
between inflammatory markers and mtDNA in subjects without NCI, and levels of
mtDNA did not differ between subjects with and without NCI. MtDNA levels preceded
pleocytosis and HIV RNA following ART interruption. Cell-free mtDNA in CSF was
strongly associated with the severity of neurocognitive dysfunction and
inflammation only in individuals with NCI. Our findings suggest that within a
subset of subjects cell-free CSF mtDNA is associated with inflammation and degree
of NCI.
PMID- 26428517
TI - Dissolution Similarity Requirements: How Similar or Dissimilar Are the Global
Regulatory Expectations?
AB - The objective of this article is to compare and contrast the international
expectations associated with the model-independent similarity factor approach to
comparing dissolution profiles. This comparison highlights globally divergent
regulatory requirements to meet local dissolution similarity requirements. In
effect, experiments customized to meet the current international regulatory
expectations for dissolution and drug release unnecessarily increase
manufacturing costs, hinder science and risk-based approaches, increase
collective regulatory burden, reduce continuous improvement and innovation, and
potentially delay patient access to urgently needed medication. Comparative
assessment of regulatory differences in applying dissolution to demonstrate
product similarity is crucial to reduce non-scientifically justified experiments
and foster collaborative harmonization among global regulatory health authorities
and the pharmaceutical industry.
PMID- 26428519
TI - Novel dysfunctional variant in ABCG2 as a cause of severe tophaceous gout:
biochemical, molecular genetics and functional analysis.
PMID- 26428520
TI - Hydroxychloroquine-related retinal toxicity.
AB - HCQ is widely used for the treatment of rheumatic diseases, particularly lupus
and RA. It is generally well tolerated, but retinopathy is a concern. Retinopathy
is rare, but is sight threatening, generally irreversible and may progress even
after cessation of therapy. Damage may be subclinical. Although a number of risk
factors have been proposed (such as duration of therapy and cumulative dose), the
many exceptions (e.g. retinopathy on low-dose HCQ, or no retinopathy after a very
large cumulative dose of HCQ) highlight our limited understanding of the disease
process. Novel technologies such as optical coherence tomography (OCT), fundus
autofluorescence (FAF) and multifocal electroretinogram (mfERG) may provide the
earliest structural and functional evidence of toxicity in these stages. Along
with the well-established technique of central visual field testing (10-2 visual
fields), these modalities are increasingly being used as part of screening
programmes. The ideal single test with high sensitivity and high specificity for
HCQ retinopathy has still not been achieved. Screening for HCQ retinopathy
remains an area of considerable debate, including issues of when, who and how to
screen. Commonly accepted risk factors include receiving >6.5 mg/kg/day or a
cumulative dose of >1000 g of HCQ, being on treatment for >5 years, having renal
or liver dysfunction, having pre-existing retinopathy and being elderly. HCQ
continues to be a valuable drug in treating rheumatic disease, but clinicians
need to be aware of the associated risks and to have arrangements in place that
would enable early detection of toxicity.
PMID- 26428518
TI - Post-diagnosis adiposity and survival among breast cancer patients: influence of
breast cancer subtype.
AB - PURPOSE: Adiposity has been linked with increased breast cancer risk and
mortality. It is established that etiologic associations for adiposity vary by
tumor subtype, but the influence of adiposity on subtype-specific survival is
unknown. METHODS: Study participants were 1,109 invasive breast cancer
participants in the population-based Carolina Breast Cancer Study, diagnosed
between 1993 and 2001, and with tissue blocks available for immunohistochemical
subtyping. General and central adiposities were assessed by body mass index (BMI)
and waist-to-hip ratio (WHR), respectively, based on in-person measurements after
diagnosis. Vital status as of 2011 was determined using the National Death Index
(median follow-up = 13.5 years). Cox proportional hazards models were used to
calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for breast
cancer (BC)-specific and all-cause mortalities. RESULTS: Among all patients, high
WHR (>=0.84), but not BMI, was associated with all-cause mortality (adjusted HR
1.50, 95% CI 1.11-2.05, <0.77 as reference). No significant association between
adiposity and BC-specific mortality was detected, although there was a suggestion
of increased mortality risk among high-BMI (>=30 kg/m(2)) patients with basal
like tumors (adjusted HR 2.44, 95% CI 0.97-6.12, <25 kg/m(2) as reference).
Quantitative differences in all-cause mortality were observed by subtype, with
BMI associated with basal-like mortality and WHR associated with luminal
mortality. The associations were attenuated by tumor characteristics.
CONCLUSIONS: Our study confirms the association of adiposity and unfavorable
overall survival in breast cancer patients and suggests that this association may
vary by intrinsic subtype and adiposity measure.
PMID- 26428521
TI - [Screening and prevention of diabetes].
AB - A valid and efficient screening for individual diabetes risk is a highly welcomed
tool in primary care and specialist medical practice. It is needed to detect
early stages of diabetes risk and prediabetes and to start interventions that
have the aim to prevent diabetes and also other chronic diseases from developing.
The oral glucose tolerance test is the gold standard, but it is difficult to
perform in an evidence-based manner in primary care. Furthermore, measuring
fasting and 2-h postprandial glucose values detects only late stages of the
pathophysiological development of type 2 diabetes. Interestingly, the 1-h glucose
value is highly predictive of future diabetes risk, but is rarely used in primary
care. Therefore, risk scores are commonly used to evaluate diabetes risk, but
unfortunately, they generally do not mirror the relevance of increased risk due
to the person's own lifestyle. Measuring waist circumference is another
possibility, because the waist is directly associated with the amount of visceral
fat, which again directly correlates with the pathophysiology of diabetes
development. A further possibility is the EZSCANTM technology. The EZSCANTM is
based on reverse iontophoresis, a new technology to detect very early forms of
peripheral neuropathies, which are commonly associated with early diabetes risk
stages. It is important to perform diabetes screening in a targeted manner, in
both medical and paramedical environments, and it is mandatory to add targeted
interventions, based on the screening evaluated diabetes risk.
PMID- 26428525
TI - [Bridging in patients with atrial fibrillation].
PMID- 26428526
TI - [Erratum to: The most frequent electrolyte disorders in the emergency department.
What must be done immediately?].
PMID- 26428527
TI - Use of communication technologies by people with type 1 diabetes in the social
networking era. A chance for improvement.
AB - AIMS: To evaluate the health-related use of Web 2.0 tools by patients with type 1
diabetes. METHODS: Cross-sectional survey assessing views and usage of the
Internet, Apps and Web 2.0. RESULTS: Number of participants: 289 (age 42.8+/-13.5
years; diabetes duration 18.4+/-12.2 years; 58.7% males; 39% with an upper
secondary or higher education level). Web 2.0 usage for health purposes was low
with 19.6% and 14% of Web 2.0 members (147; 50.9%) having health-related contacts
and posting health comments. Health-related Apps were used by 35.4% of Smartphone
owners (161; 55.7%). 75.3% patients would share information online with
professionals, preferably through e-mail (78.7%) rather than Facebook (47.7%).
141 (66.5%) of those willing to share information would participate in a
professional-moderated Facebook group. CONCLUSIONS: Web 2.0 and Apps usage for
health purposes is low. The difference between the use of Web 2.0 networks and
the willingness to participate in professional-moderated Web 2.0 groups points to
the need of a higher implication of health professionals in promoting Web 2.0
technologies if these are to be adopted in a clinical setting. Currently, e-mail
is the tool to be considered when aiming to increase online communication with
patients with type 1 diabetes.
PMID- 26428528
TI - Crataegus songarica methanolic extract accelerates enzymatic status in kidney and
heart tissue damage in albino rats and its in vitro cytotoxic activity.
AB - CONTEXT: Crataegus songarica K. Koch (Rosaceae) has been used in folk medicine to
treat various diseases. OBJECTIVE: This study evaluates the effect of C.
songarica methanol extract on the kidney and heart tissue damage of albino rats,
and to determine cytotoxic activity of various extracts of songarica on various
human cancer cell lines. MATERIALS AND METHODS: Rats were divided into six
groups, Group I received water only; Group II received CCl4 (1 mL/kg b wt)
intraperitoneal; C. songarica extract (at doses of 100, 200 and 300 mg/kg b wt)
orally for 15 days. Cytotoxic activity was determined by SRB method using MCF-7,
HeLa, HepG2, SF-295, SW480 and IMR-32 cell lines. RESULTS: Compared with CCl4
group, administration of C. songarica extract at the dose of 300 mg/kg b wt,
significantly decreases serum creatinine (59.74%), urea (40.23%) and cholesterol
(54 mg/dL), MDA (0.007 nmol/mg protein) in kidney and (0.025 nmol/mg protein) in
heart tissue, along with evaluation of GSH (209.79 +/- 54.6), GR (111.45 +/-
2.84), GPx (94.01 +/- 14.80), GST (201.71) in kidney tissue and GSH (51.47 +/-
1.47), GR (45.42 +/- 6.69), GPx (77.19 +/- 10.94), GST (49.89) in heart tissue.
In addition, methanol, ethanol and ethyl acetate extracts exhibited potent
anticancer activity on six cancer cell lines with IC50 values ranging from 28.57
to 85.106 ug/mL. DISCUSSION AND CONCLUSION: Crataegus songarica methanol extract
has a potential antioxidant effect as it protects the kidney and heart tissue
against CCl4-induced toxicity, prevents DNA damage and showed strong anticancer
activity.
PMID- 26428529
TI - Qualitative interpretation of PET scans using a Likert scale to assess neck node
response to radiotherapy in head and neck cancer.
AB - PURPOSE: The aim of this study was to determine whether PET scans after
radiotherapy (RT), visually interpreted as equivocal regarding metabolic neck
node response can be used to accurately categorize patients as responders or
nonresponders using a Likert scale and/or maximum standardized uptake value
(SUVmax). Other aims were to determine the performance of different methods for
assessing post-RT PET scans (visual inspection, a Likert scale and SUVmax) and to
establish whether any method is superior in predicting regional control (RC) and
overall survival (OS). METHODS: In 105 patients with neck node-positive head and
neck cancer, the neck node response was evaluated by FDG PET/CT 6 weeks after RT.
The scans were clinically assessed by visual inspection and, for the purposes of
this analysis, re-evaluated using the Deauville criteria, a five-point Likert
scale previously used in lymphoma studies. In addition, SUVmax was determined.
RESULTS: All assessment methods were able to significantly predict RC but not OS.
The methods were also able to significantly predict remission of tumour after
completion of RT. Of the 105 PET scans, 19 were judged as equivocal on visual
inspection. The Likert scale was preferable to SUVmax for grouping patients as
responders or nonresponders. CONCLUSION: All methods (visual inspection, SUVmax
and the Likert scale) identified responders and nonresponders and predicted RC. A
Likert scale is a promising tool to reduce to a minimum the problem of PET scans
judged as equivocal. Consensus regarding qualitative assessment would facilitate
PET reporting in clinical practice.
PMID- 26428530
TI - Periodic model of an LTA framework.
AB - Zeolites are a group of microporous aluminosilicate frameworks with numerous
applications in, for example, catalysis and ion-exchange and sorption processes.
One of the most important tools for analyzing the properties of zeolite
structures is vibrational spectroscopy. However, the complexity of these
structures often leads to difficulties when attempting to interpret the resulting
spectra, so an additional complementary tool is required: computational methods.
The aim of this study was to formulate a simplified periodic model of an LTA
framework containing alkali metal cations (either Li(+), Na(+), K(+), Rb(+), or
Cs(+)) and to perform a set of ab initio calculations aimed at assessing the
influence of these cations on the properties of the vibrational spectra of the
LTA framework. Additionally, chemical bonding was analyzed by means of electron
density topology analysis. Results obtained were compared with experimental
spectra for alkali metal forms of zeolite A. It was found that the vibrational
spectra obtained using the proposed model agree well with the corresponding
experimentally derived spectra, meaning that the model can be used to analyze
real spectra in detail.
PMID- 26428531
TI - Does glimepiride alter the pharmacokinetics of sildenafil citrate in diabetic
nephropathy animals: investigating mechanism of interaction by molecular modeling
studies.
AB - The present study evaluates possible drug interactions between glimepiride (GLIM)
and sildenafil citrate (SIL) in streptozotocin (STZ)-induced diabetic
nephropathic (DN) animals and also postulates the possible mechanism of
interaction based on molecular modeling studies. Diabetic nephropathy was induced
by single dose of STZ (60 mg kg(-1), i.p.) and was confirmed by assessing blood
and urine biochemical parameters 28 days after induction. Selected DN animals
were used to explore the drug interaction between GLIM (0.5 mg kg(-1), p.o.) and
SIL (2.5 mg kg(-1), p.o.) on the 29th and 70th day of the protocol. Possible drug
interaction was assessed by evaluating the plasma drug concentration using HPLC
UV and changes in biochemical parameters in blood and urine were also determined.
The mechanism of the interaction was postulated from the results of a molecular
modeling study using the Maestro module of Schrodinger software. DN was confirmed
as there was significant alteration in blood and urine biochemical parameters in
STZ-treated groups. The concentration of SIL increased significantly (P < 0.001)
in rat plasma when co-administered with GLIM on the 70th day of the protocol.
Molecular modeling revealed important interactions with rat serum albumin and
CYP2C9. GLIM has a strong hydrophobic interaction with binding site residues of
rat serum albumin compared to SIL, whereas for CYP2C9, GLIM forms a stronger
hydrogen bond than SIL with polar contacts and hydrophobic interactions. The
present study concludes that bioavailability of SIL increases when co
administered chronically with GLIM in the management of DN animals, and the
mechanism is supported by molecular modeling studies.
PMID- 26428532
TI - Roles of the NMDA Receptor and EAAC1 Transporter in the Modulation of
Extracellular Glutamate by Low and High Affinity AMPA Receptors in the Cerebellum
in Vivo: Differential Alteration in Chronic Hyperammonemia.
AB - The roles of high- and low-affinity AMPA receptors in modulating extracellular
glutamate in the cerebellum remain unclear. Altered glutamatergic
neurotransmission is involved in neurological alterations in hyperammonemia,
which differently affects high- and low-affinity AMPA receptors. The aims were to
assess by in vivo microdialysis (a) the effects of high- and low-affinity AMPA
receptor activation on extracellular glutamate in the cerebellum; (b) whether
chronic hyperammonemia alters extracellular glutamate modulation by high- and/or
low-affinity AMPA receptors; and (c) the contribution of NMDA receptors and EAAC1
transporter to AMPA-induced changes in extracellular glutamate. In control rats,
high affinity receptor activation does not affect extracellular glutamate but
increases glutamate if NMDA receptors are blocked. Low affinity AMPA receptor
activation increases transiently extracellular glutamate followed by reduction
below basal levels and return to basal values. The reduction is associated with
transient increased membrane expression of EAAC1 and is prevented by blocking
NMDA receptors. Blocking NMDA receptors with MK-801 induces a transient increase
in extracellular glutamate which is associated with reduced membrane expression
of EAAC1 followed by increased membrane expression of the glutamate transporter
GLT-1. Chronic hyperammonemia does not affect responses to activation of low
affinity AMPA receptors. Activation of high affinity AMPA receptors increases
extracellular glutamate in hyperammonemic rats by an NMDA receptor-dependent
mechanism. In conclusion, these results show that there is a tightly controlled
interplay between AMPA and NMDA receptors and an EAAC1 transporter in controlling
extracellular glutamate. Hyperammonemia alters high- but not low-affinity AMPA
receptors.
PMID- 26428533
TI - Probing the kinetic landscape of Hox transcription factor-DNA binding in live
cells by massively parallel Fluorescence Correlation Spectroscopy.
AB - Hox genes encode transcription factors that control the formation of body
structures, segment-specifically along the anterior-posterior axis of metazoans.
Hox transcription factors bind nuclear DNA pervasively and regulate a plethora of
target genes, deploying various molecular mechanisms that depend on the
developmental and cellular context. To analyze quantitatively the dynamics of
their DNA-binding behavior we have used confocal laser scanning microscopy
(CLSM), single-point fluorescence correlation spectroscopy (FCS), fluorescence
cross-correlation spectroscopy (FCCS) and bimolecular fluorescence
complementation (BiFC). We show that the Hox transcription factor Sex combs
reduced (Scr) forms dimers that strongly associate with its specific fork head
binding site (fkh250) in live salivary gland cell nuclei. In contrast, dimers of
a constitutively inactive, phospho-mimicking variant of Scr show weak, non
specific DNA-binding. Our studies reveal that nuclear dynamics of Scr is complex,
exhibiting a changing landscape of interactions that is difficult to characterize
by probing one point at a time. Therefore, we also provide mechanistic evidence
using massively parallel FCS (mpFCS). We found that Scr dimers are predominantly
formed on the DNA and are equally abundant at the chromosomes and an introduced
multimeric fkh250 binding-site, indicating different mobilities, presumably
reflecting transient binding with different affinities on the DNA. Our proof-of
principle results emphasize the advantages of mpFCS for quantitative
characterization of fast dynamic processes in live cells.
PMID- 26428534
TI - Mitochondrial implications in bulbospinal muscular atrophy (Kennedy disease).
AB - There is increasing evidence that mitochondrial functions are secondarily
disturbed in bulbospinal muscular atrophy (BSMA). This review focuses on the
relation between BSMA and the effect of the expanded polyglutamine (poly-Q)
androgen receptor (AR) on mitochondrial functions. Mitochondrial functions in
bulbospinal muscular atrophy (SBMA) are affected on the molecular, clinical, and
therapeutic level. On the molecular level there is down-regulation of various
nuclear-DNA-encoded mitochondrial proteins by mutant androgen receptor (mAR),
colocalization of the mAR with various mitochondrial proteins, association of mAR
aggregates with mitochondria resulting in abnormal distribution of mitochondria,
mtDNA depletion or multiple mtDNA deletions, mitochondrial membrane
depolarization, increase in reactive oxidative species, and activation of the
mitochondrial caspase pathway. On the clinical level various mitochondrial
disorders mimic SBMA, and on the therapeutic level pioglitazone expresses PPAR
gamma, cyclosporine-A restores mitochondrial membrane potentials, coenzyme-Q and
idebenone reduce oxidative stress, and geldanamycin up-regulates protective
mitochondrial heat shock proteins. In conclusion, in BSMA mitochondrial
dysfunction results from various interactions of elongated poly-Q AR with
mitochondria, mitochondrial proteins, nuclear or mitochondrial DNA, causing
oxidative stress, decreased mitochondrial membrane potential, or activation of
the mitochondrial caspase pathway. Additionally, mitochondrial disease may mimic
BSMA and therapeutic approaches may depend on modifications of mitochondrial
pathways.
PMID- 26428535
TI - Mathematics and biology: The ultimate interface?
PMID- 26428536
TI - Editorial.
AB - Preparing this ambitious Special Issue has challenged everyone involved: authors,
reviewers, and guest editors. The editors solicited contributions from many
leading figures in a broad array of scientific and philosophical disciplines,
with emphasis on phenomenological approaches to philosophy (see Section I). The
motivating force was the conviction that if we could find a viable bridge for the
gap between the "two cultures"(1) of science and philosophy, fundamental problems
in each camp could be addressed more fruitfully than ever before and a new kind
of science be born. We believe the unprecedented cross-fertilization of ideas
from this initiative may furnish seeds from which that new, better integrated,
and more effective approach to science may arise. This Special Issue consists of
forty papers. For each one, multiple reviewers were solicited, with at least one
reviewer from each "culture" (a scientist and a philosopher). In many cases,
several rounds of revision were carried out. Needless to say, this required great
patience and dedication of all participants. The editors gratefully acknowledge
the contributions of our authors, and of our anonymous reviewers, who worked long
and hard on the papers we sent them with no compensation for their efforts. We
also wish to thank the Elsevier editorial and production team for the support
they gave us in bringing this project to fruition. We would now like to offer a
synoptic overview of the Special Issue, proceeding section by section and paper
by paper. Our hope is that the reader will find this unique effort to marry
science and philosophy both meaningful and enjoyable.
PMID- 26428537
TI - Ruthenium(II) p-cymene complex bearing 2,2'-dipyridylamine targets caspase 3
deficient MCF-7 breast cancer cells without disruption of antitumor immune
response.
AB - [Ru(eta(6)-p-cym)Cl{dpa(CH2)4COOEt}][PF6] (cym=cymene; dpa=2,2'-dipyridylamine;
complex 2) was prepared and characterized by elemental analysis, IR and
multinuclear NMR spectroscopy, as well as ESI-MS and X-ray structural analysis.
The structural analog without a side chain [Ru(eta(6)-p-cym)Cl(dpa)][PF6] (1) as
well as 2 were investigated in vitro against 518A2, SW480, 8505C, A253 and MCF-7
cell lines. Complex 1 is active against all investigated tumor cell lines while
the activity of compound 2 is limited only to caspase 3 deficient MCF-7 breast
cancer cells, however, both are less active than cisplatin. As CD4(+)Th cells are
necessary to trigger all the immune effector mechanisms required to eliminate
tumor cells, besides testing the in vitro antitumor activity of 1 and 2, the
effect of ruthenium(II) complexes on the cells of the adaptive immune system have
also been evaluated. Importantly, complex 1 applied in concentrations which were
effective against tumor cells did not affect immune cell viability, nor did exert
a general immunosuppressive effect on cytokine production. Thus, beneficial
characteristics of 1 might contribute to the overall therapeutic properties of
the complex.
PMID- 26428539
TI - Population Screening and Prevention Strategies for Thalassemias and other
Hemoglobinopathies of Eastern India: Experience of 18,166 cases.
AB - We evaluated population screening programs (1999-2011), conducted by the
Thalassaemia Foundation, Kolkata, India, for the first time in Eastern India in
different districts of West Bengal, for prevention of thalassemia comprising
screening of heterozygotes and beta-thalassemia intermedia (beta-TI) cases
[beta(+), beta(++), beta(0)/beta(+), beta(E)/beta(E) (codon 26 or HBB: c.79G >
A), Hb-E-beta-thalassemia (Hb E-beta-thal)]. Among 18,166 cases, we found 2092
heterozygotes and 2245 beta-TI individuals (who had no information about their
disorders). Results were evaluated with standard hematological analyses including
erythrocyte indices, hemoglobin (Hb) typing and quantification. Participants were
divided into five groups (children, pre-marriage cases, pre-pregnancy cases,
affected family members, pregnant women). The objectives of this evaluation were
to fix cut-off values of red blood cells (RBCs), mean corpuscular volume (MCV),
mean corpuscular Hb (MCH), red blood cell distribution width (RDW) and Hb A2, as
the standard World Health Organization (WHO) guidelines were not strictly
followed in mass-scale screening programs. We have observed many dilemmas in
considering the status of the thalassemia subject, due to presence of some other
clinical conditions such as iron deficiency anemia, alpha-thalassemia (alpha
thal), delta-thalassemia (delta-thal), clinically silent Hb variants, and some
cases of non hemoglobinopathies (such as pregnancy) along with thalassemia. The
MCV values varied greatly in different conditions of hemoglobinopathies, whereas
MCH provided a more stable measurement. We found an MCH value of <27.0 pg is a
suitable cut-off point for screening in this population. Participants with an MCH
of <27.0 pg should be investigated further to confirm or exclude a diagnosis of
beta-thal trait.
PMID- 26428540
TI - Occlusal traits in children with neurofibromatosis type 1.
AB - OBJECTIVES: Literature is poor of data about the occlusion in children affected
by neurofibromatosis type 1 (NF1). This case-control study investigated the
occlusal traits in a group of children with NF1. SETTING AND SAMPLE POPULATION: A
hundred and fifteen children with NF1 were enrolled; non-NF1 controls were
sequentially selected among subjects referred to the Pediatric Dentistry
Department. MATERIAL AND METHODS: All patients underwent a clinical dental
examination and a panoramic radiography. The following orthodontic variables were
considered: molar relationship, overjet, overbite, cross-bite, scissor bite, and
crowding/spacing. RESULTS: Class III molar relationship resulted significantly (p
= 0.01) more common in children with NF1 than in the control group as well as the
unilateral posterior cross-bite (p = 0.0017). Forty-three children with NF1
(37.3%) showed radiographic abnormalities; in one case, a plexiform neurofibroma
was detected. CONCLUSIONS: An early orthodontic evaluation might be planned in
the management of children with NF1 to prevent or decrease the need for extensive
orthodontic interventions.
PMID- 26428538
TI - On scattered waves and lipid domains: detecting membrane rafts with X-rays and
neutrons.
AB - In order to understand the biological role of lipids in cell membranes, it is
necessary to determine the mesoscopic structure of well-defined model membrane
systems. Neutron and X-ray scattering are non-invasive, probe-free techniques
that have been used extensively in such systems to probe length scales ranging
from angstroms to microns, and dynamics occurring over picosecond to millisecond
time scales. Recent developments in the area of phase separated lipid systems
mimicking membrane rafts will be presented, and the underlying concepts of the
different scattering techniques used to study them will be discussed in detail.
PMID- 26428541
TI - Disparities in conditional net survival among non-Hodgkin lymphoma survivors: a
population-based analysis.
AB - We evaluated the association of baseline prognostic factors with conditional net
survival among survivors of six subtypes non-Hodgkin lymphoma using the SEER
program data from 2000-2012. Among 2-year survivors, further prognosis markedly
improved in Burkitt's (BL) and diffuse large B-cell lymphoma (DLBCL), and became
the same as for follicular lymphoma (5-year net survival >= 85%). Mantle cell
lymphoma (MCL) demonstrated the worst prognosis of all studied histologies up to
5 years of survivorship. Age and stage lost prognostic significance in BL within
2 years from diagnosis. Racial disparities in net survival disappeared within 2
years for all subtypes, except in chronic lymphocytic leukemia, where black
patients had persistently worse prognosis, and in MCL, where they had
unexpectedly better prognosis than other races after 2 years. Many baseline
factors may lose their initial prognostic value for lymphoma survivors, which
should be considered when counseling patients about their prognosis and long-term
surveillance.
PMID- 26428546
TI - Towards witnessing quantum effects in complex molecules.
AB - Whether many-body objects like organic molecules can exhibit full quantum
behaviour, including entanglement, is an open fundamental question. We present a
generic theoretical protocol for entangling two organic molecules, such as
dibenzoterrylene in anthracene. The availability of organic dye molecules with
two-level energy structures characterised by sharp and intense emission lines are
characteristics that position them favourably as candidates for quantum
information processing technologies involving single-photons. Quantum
entanglement can in principle be generated between several organic molecules by
carefully interfering their photoluminescence spectra. Major milestones have been
achieved in the last 10 years showcasing entanglement in diverse systems
including ions, cold atoms, superconductors, photons, quantum dots and NV-centres
in diamond, but not yet in molecules.
PMID- 26428547
TI - Erratum to: Vertical scapular osteotomy in congenital high scapula.
PMID- 26428548
TI - Postharvest Biological Control of Colletotrichum acutatum on Apple by Bacillus
subtilis HM1 and the Structural Identification of Antagonists.
AB - Bacillus subtilis HM1 was isolated from the rhizosphere region of halophytes for
its antifungal activity against Colletotrichum acutatum, the causative agent of
anthracnose. Treatment of postharvest apples with the cell culture or with a cell
free culture supernatant reduced disease severity 80.7% and 69.4%, respectively.
Both treatments also exhibited antifungal activity against various
phytopathogenic fungi in vitro. The antifungal substances were purified and
analyzed by acid precipitation, gel filtration, high-performance liquid
chromatography, and matrix-assisted laser desorption ionization-time of flight
mass spectrometry (MALDI-TOF MS). Three compounds were identified as fengycin,
iturin, and surfactin. The MALDI-TOF/ TOF mass spectrum revealed the presence of
cyclized fengycin homologs A and B, which were distinguishable on the basis of
the presence of either alanine or valine, respectively, at position 6 of the
peptide sequence. In addition, the cyclized structure of fengycin was shown to
play a critical role in antifungal activity.
PMID- 26428550
TI - The Lag of the Proliferative Aging Clock Underlies the Lifespan-Extending Effect
of Calorie Restriction.
AB - BACKGROUND: The nature of the life-extending effect of calorie restriction (CR)
is an unsolved problem in biology since 30 years of the last century.
Furthermore, many different factors that cause analogous life-extending effect,
so called CR-mimetic factors, have been found. They increase the lifespan of
different animal species (repeatedly in invertebrates) and therefore remain in
the forefront of anti-aging researches. The aims of this paper is to find an
overarching solution for the nature of CR and all CR-mimetic factors and to
analyze the consequences following this phenomenon. METHODS: The analysis of
empirical scientific data, which concern aging process and boundary areas from
the point of view of the bioenergetics theory of aging. RESULTS: "Anything that
affects a living system that slows (accelerates) the rate of cell division
entails extending (reducing) life duration" is this overarching solution. CR is
one of such factors that cause a retardation in the rate of cell divisions due to
the shortage in 'construction materials' necessary for doubling cell mass during
reduplication. This put a brake on realization of the aging program. To draw this
conclusion, a new concept of the proliferative aging clock based on bioenergetics
theory of aging was put forward. This clock governs the rate of the aging process
via programmed, proliferative dependent and stepwise bioenergetics decline.
CONCLUSION: The mechanism of the life-extending effect of CR and CR-mimetic
factors is not related to that of natural aging, therefore this unable to be the
basis for elaboration of radical remedy for senescence. However, both the CR and
some of CR-mimetic factors can undoubtedly lead to human life extension: our
organism differs from that of the other mammals only slightly. It is the
wellbeing and vulnerability of such extended life that are under consideration.
To achieve a healthy and unlimited life it is necessary to reprogram gene
expression so that cell bioenergetics levels either remain at a previous level
after cell division, which will stop aging, or else grow, which will result in
organism rejuvenation.
PMID- 26428549
TI - Variation in serotonin neurotransmission genes affects neural activation during
response inhibition in adolescents and young adults with ADHD and healthy
controls.
AB - OBJECTIVES: Deficits in response inhibition have been associated with attention
deficit/hyperactivity disorder (ADHD). Given the role of serotonin in ADHD and
impulsivity, we postulated that genetic variants within the serotonin pathway
might influence response inhibition. METHODS: We measured neural activation
during stop-signal task performance in adolescents with ADHD (N = 185), their
unaffected siblings (N = 111), and healthy controls (N = 124), and investigated
the relationship of two serotonin gene polymorphisms (the rs6296 SNP of the HTR1B
gene and HTTLPR variants of the 5-HTT gene) with the neural correlates of
response inhibition. RESULTS: The whole-brain analyses demonstrated large scale
neural activation differences in the inferior and medial frontal and
temporal/parietal regions of the response inhibition network between the
different variants of both the HTR1B and 5HTT genes. Activation in these regions
was significantly associated with stop-task performance, but not with ADHD
diagnosis or severity. No associations were found between HTR1B and 5HTT variants
and ADHD or ADHD-related neural activation. CONCLUSIONS: These results provide
novel evidence that serotonin may play an important role in the neurobiology of
response inhibition. Although response inhibition is strongly linked to ADHD,
serotonin linked genetic variants associated with response inhibition and its
neural correlates do not explain variance of the ADHD phenotype.
PMID- 26428551
TI - Looking forward and looking back: the balancing act in new drug user designs for
pharmacoepidemiological research.
PMID- 26428552
TI - Editorial: The pre-history of Chaos-An Interdisciplinary Journal of Nonlinear
Science.
PMID- 26428553
TI - Introduction to Focus Issue: The 25th Anniversary of Chaos: Perspectives on
Nonlinear Science-Past, Present, and Future.
PMID- 26428554
TI - Quantum and wave dynamical chaos in superconducting microwave billiards.
AB - Experiments with superconducting microwave cavities have been performed in our
laboratory for more than two decades. The purpose of the present article is to
recapitulate some of the highlights achieved. We briefly review (i) results
obtained with flat, cylindrical microwave resonators, so-called microwave
billiards, concerning the universal fluctuation properties of the eigenvalues of
classically chaotic systems with no, a threefold and a broken symmetry; (ii)
summarize our findings concerning the wave-dynamical chaos in three-dimensional
microwave cavities; (iii) present a new approach for the understanding of the
phenomenon of dynamical tunneling which was developed on the basis of experiments
that were performed recently with unprecedented precision, and finally, (iv) give
an insight into an ongoing project, where we investigate universal properties of
(artificial) graphene with superconducting microwave photonic crystals that are
enclosed in a microwave resonator, i.e., so-called Dirac billiards.
PMID- 26428555
TI - Thirty years of turnstiles and transport.
AB - To characterize transport in a deterministic dynamical system is to compute exit
time distributions from regions or transition time distributions between regions
in phase space. This paper surveys the considerable progress on this problem over
the past thirty years. Primary measures of transport for volume-preserving maps
include the exiting and incoming fluxes to a region. For area-preserving maps,
transport is impeded by curves formed from invariant manifolds that form partial
barriers, e.g., stable and unstable manifolds bounding a resonance zone or
cantori, the remnants of destroyed invariant tori. When the map is exact volume
preserving, a Lagrangian differential form can be used to reduce the computation
of fluxes to finding a difference between the actions of certain key orbits, such
as homoclinic orbits to a saddle or to a cantorus. Given a partition of phase
space into regions bounded by partial barriers, a Markov tree model of transport
explains key observations, such as the algebraic decay of exit and recurrence
distributions.
PMID- 26428556
TI - Dynamical disease: Challenges for nonlinear dynamics and medicine.
AB - Dynamical disease refers to illnesses that are associated with striking changes
in the dynamics of some bodily function. There is a large literature in
mathematics and physics which proposes mathematical models for the physiological
systems and carries out analyses of the properties of these models using
nonlinear dynamics concepts involving analyses of the stability and bifurcations
of attractors. This paper discusses how these concepts can be applied to
medicine.
PMID- 26428557
TI - Invariant manifolds and global bifurcations.
AB - Invariant manifolds are key objects in describing how trajectories partition the
phase spaces of a dynamical system. Examples include stable, unstable, and center
manifolds of equilibria and periodic orbits, quasiperiodic invariant tori, and
slow manifolds of systems with multiple timescales. Changes in these objects and
their intersections with variation of system parameters give rise to global
bifurcations. Bifurcation manifolds in the parameter spaces of multi-parameter
families of dynamical systems also play a prominent role in dynamical systems
theory. Much progress has been made in developing theory and computational
methods for invariant manifolds during the past 25 years. This article highlights
some of these achievements and remaining open problems.
PMID- 26428558
TI - Chaos, patterns, coherent structures, and turbulence: Reflections on nonlinear
science.
AB - The paradigms of nonlinear science were succinctly articulated over 25 years ago
as deterministic chaos, pattern formation, coherent structures, and
adaptation/evolution/learning. For chaos, the main unifying concept was universal
routes to chaos in general nonlinear dynamical systems, built upon a framework of
bifurcation theory. Pattern formation focused on spatially extended nonlinear
systems, taking advantage of symmetry properties to develop highly quantitative
amplitude equations of the Ginzburg-Landau type to describe early nonlinear
phenomena in the vicinity of critical points. Solitons, mathematically precise
localized nonlinear wave states, were generalized to a larger and less precise
class of coherent structures such as, for example, concentrated regions of
vorticity from laboratory wake flows to the Jovian Great Red Spot. The
combination of these three ideas was hoped to provide the tools and concepts for
the understanding and characterization of the strongly nonlinear problem of fluid
turbulence. Although this early promise has been largely unfulfilled, steady
progress has been made using the approaches of nonlinear science. I provide a
series of examples of bifurcations and chaos, of one-dimensional and two
dimensional pattern formation, and of turbulence to illustrate both the progress
and limitations of the nonlinear science approach. As experimental and
computational methods continue to improve, the promise of nonlinear science to
elucidate fluid turbulence continues to advance in a steady manner, indicative of
the grand challenge nature of strongly nonlinear multi-scale dynamical systems.
PMID- 26428559
TI - Cycles, randomness, and transport from chaotic dynamics to stochastic processes.
AB - An overview of advances at the frontier between dynamical systems theory and
nonequilibrium statistical mechanics is given. Sensitivity to initial conditions
is a mechanism at the origin of dynamical randomness-alias temporal disorder-in
deterministic dynamical systems. In spatially extended systems, sustaining
transport processes, such as diffusion, relationships can be established between
the characteristic quantities of dynamical chaos and the transport coefficients,
bringing new insight into the second law of thermodynamics. With methods from
dynamical systems theory, the microscopic time-reversal symmetry can be shown to
be broken at the statistical level of description in nonequilibrium systems. In
this way, the thermodynamic entropy production turns out to be related to
temporal disorder and its time asymmetry away from equilibrium.
PMID- 26428560
TI - Self-organization of pulsing and bursting in a CO2 laser with opto-electronic
feedback.
AB - We report a detailed investigation of the stability of a CO2 laser with feedback
as described by a six-dimensional rate-equations model which provides
satisfactory agreement between numerical and experimental results. We focus on
experimentally accessible parameters, like bias voltage, feedback gain, and the
bandwidth of the feedback loop. The impact of decay rates and parameters
controlling cavity losses are also investigated as well as control planes which
imply changes of the laser physical medium. For several parameter combinations,
we report stability diagrams detailing how laser spiking and bursting is
organized over extended intervals. Laser pulsations are shown to emerge organized
in several hitherto unseen regular and irregular phases and to exhibit a much
richer and complex range of behaviors than described thus far. A significant
observation is that qualitatively similar organization of laser spiking and
bursting can be obtained by tuning rather distinct control parameters, suggesting
the existence of unexpected symmetries in the laser control space.
PMID- 26428561
TI - From globally coupled maps to complex-systems biology.
AB - Studies of globally coupled maps, introduced as a network of chaotic dynamics,
are briefly reviewed with an emphasis on novel concepts therein, which are
universal in high-dimensional dynamical systems. They include clustering of
synchronized oscillations, hierarchical clustering, chimera of synchronization
and desynchronization, partition complexity, prevalence of Milnor attractors,
chaotic itinerancy, and collective chaos. The degrees of freedom necessary for
high dimensionality are proposed to equal the number in which the combinatorial
exceeds the exponential. Future analysis of high-dimensional dynamical systems
with regard to complex-systems biology is briefly discussed.
PMID- 26428562
TI - Complex network based techniques to identify extreme events and (sudden)
transitions in spatio-temporal systems.
AB - We present here two promising techniques for the application of the complex
network approach to continuous spatio-temporal systems that have been developed
in the last decade and show large potential for future application and
development of complex systems analysis. First, we discuss the transforming of a
time series from such systems to a complex network. The natural approach is to
calculate the recurrence matrix and interpret such as the adjacency matrix of an
associated complex network, called recurrence network. Using complex network
measures, such as transitivity coefficient, we demonstrate that this approach is
very efficient for identifying qualitative transitions in observational data,
e.g., when analyzing paleoclimate regime transitions. Second, we demonstrate the
use of directed spatial networks constructed from spatio-temporal measurements of
such systems that can be derived from the synchronized-in-time occurrence of
extreme events in different spatial regions. Although there are many
possibilities to investigate such spatial networks, we present here the new
measure of network divergence and how it can be used to develop a prediction
scheme of extreme rainfall events.
PMID- 26428563
TI - Nonlinear time-series analysis revisited.
AB - In 1980 and 1981, two pioneering papers laid the foundation for what became known
as nonlinear time-series analysis: the analysis of observed data-typically
univariate-via dynamical systems theory. Based on the concept of state-space
reconstruction, this set of methods allows us to compute characteristic
quantities such as Lyapunov exponents and fractal dimensions, to predict the
future course of the time series, and even to reconstruct the equations of motion
in some cases. In practice, however, there are a number of issues that restrict
the power of this approach: whether the signal accurately and thoroughly samples
the dynamics, for instance, and whether it contains noise. Moreover, the
numerical algorithms that we use to instantiate these ideas are not perfect; they
involve approximations, scale parameters, and finite-precision arithmetic, among
other things. Even so, nonlinear time-series analysis has been used to great
advantage on thousands of real and synthetic data sets from a wide variety of
systems ranging from roulette wheels to lasers to the human heart. Even in cases
where the data do not meet the mathematical or algorithmic requirements to assure
full topological conjugacy, the results of nonlinear time-series analysis can be
helpful in understanding, characterizing, and predicting dynamical systems.
PMID- 26428564
TI - Synchronization of chaotic systems.
AB - We review some of the history and early work in the area of synchronization in
chaotic systems. We start with our own discovery of the phenomenon, but go on to
establish the historical timeline of this topic back to the earliest known paper.
The topic of synchronization of chaotic systems has always been intriguing, since
chaotic systems are known to resist synchronization because of their positive
Lyapunov exponents. The convergence of the two systems to identical trajectories
is a surprise. We show how people originally thought about this process and how
the concept of synchronization changed over the years to a more geometric view
using synchronization manifolds. We also show that building synchronizing systems
leads naturally to engineering more complex systems whose constituents are
chaotic, but which can be tuned to output various chaotic signals. We finally end
up at a topic that is still in very active exploration today and that is
synchronization of dynamical systems in networks of oscillators.
PMID- 26428565
TI - Recent advances in symmetric and network dynamics.
AB - We summarize some of the main results discovered over the past three decades
concerning symmetric dynamical systems and networks of dynamical systems, with a
focus on pattern formation. In both of these contexts, extra constraints on the
dynamical system are imposed, and the generic phenomena can change. The main
areas discussed are time-periodic states, mode interactions, and non-compact
symmetry groups such as the Euclidean group. We consider both dynamics and
bifurcations. We summarize applications of these ideas to pattern formation in a
variety of physical and biological systems, and explain how the methods were
motivated by transferring to new contexts Rene Thom's general viewpoint, one
version of which became known as "catastrophe theory." We emphasize the role of
symmetry-breaking in the creation of patterns. Topics include equivariant Hopf
bifurcation, which gives conditions for a periodic state to bifurcate from an
equilibrium, and the H/K theorem, which classifies the pairs of setwise and
pointwise symmetries of periodic states in equivariant dynamics. We discuss mode
interactions, which organize multiple bifurcations into a single degenerate
bifurcation, and systems with non-compact symmetry groups, where new technical
issues arise. We transfer many of the ideas to the context of networks of coupled
dynamical systems, and interpret synchrony and phase relations in network
dynamics as a type of pattern, in which space is discretized into finitely many
nodes, while time remains continuous. We also describe a variety of applications
including animal locomotion, Couette-Taylor flow, flames, the Belousov
Zhabotinskii reaction, binocular rivalry, and a nonlinear filter based on
anomalous growth rates for the amplitude of periodic oscillations in a feed
forward network.
PMID- 26428566
TI - From chemical systems to systems chemistry: Patterns in space and time.
AB - We present a brief, idiosyncratic overview of the past quarter century of
progress in nonlinear chemical dynamics and discuss what we view as the most
exciting recent developments and some challenges and likely areas of progress in
the next 25 years.
PMID- 26428567
TI - Some new surprises in chaos.
AB - "Chaos is found in greatest abundance wherever order is being sought.It always
defeats order, because it is better organized"Terry PratchettA brief review is
presented of some recent findings in the theory of chaotic dynamics. We also
prove a statement that could be naturally considered as a dual one to the
Poincare theorem on recurrences. Numerical results demonstrate that some parts of
the phase space of chaotic systems are more likely to be visited earlier than
other parts. A new class of chaotic focusing billiards is discussed that clearly
violates the main condition considered to be necessary for chaos in focusing
billiards.
PMID- 26428568
TI - Exploiting chaos for applications.
AB - We discuss how understanding the nature of chaotic dynamics allows us to control
these systems. A controlled chaotic system can then serve as a versatile pattern
generator that can be used for a range of application. Specifically, we will
discuss the application of controlled chaos to the design of novel computational
paradigms. Thus, we present an illustrative research arc, starting with ideas of
control, based on the general understanding of chaos, moving over to applications
that influence the course of building better devices.
PMID- 26428569
TI - Dynamics of globally coupled oscillators: Progress and perspectives.
AB - In this paper, we discuss recent progress in research of ensembles of mean field
coupled oscillators. Without an ambition to present a comprehensive review, we
outline most interesting from our viewpoint results and surprises, as well as
interrelations between different approaches.
PMID- 26428570
TI - Lagrangian based methods for coherent structure detection.
AB - There has been a proliferation in the development of Lagrangian analytical
methods for detecting coherent structures in fluid flow transport, yielding a
variety of qualitatively different approaches. We present a review of four
approaches and demonstrate the utility of these methods via their application to
the same sample analytic model, the canonical double-gyre flow, highlighting the
pros and cons of each approach. Two of the methods, the geometric and
probabilistic approaches, are well established and require velocity field data
over the time interval of interest to identify particularly important material
lines and surfaces, and influential regions, respectively. The other two
approaches, implementing tools from cluster and braid theory, seek coherent
structures based on limited trajectory data, attempting to partition the flow
transport into distinct regions. All four of these approaches share the common
trait that they are objective methods, meaning that their results do not depend
on the frame of reference used. For each method, we also present a number of
example applications ranging from blood flow and chemical reactions to ocean and
atmospheric flows.
PMID- 26428571
TI - Defining chaos.
AB - In this paper, we propose, discuss, and illustrate a computationally feasible
definition of chaos which can be applied very generally to situations that are
commonly encountered, including attractors, repellers, and non-periodically
forced systems. This definition is based on an entropy-like quantity, which we
call "expansion entropy," and we define chaos as occurring when this quantity is
positive. We relate and compare expansion entropy to the well-known concept of
topological entropy to which it is equivalent under appropriate conditions. We
also present example illustrations, discuss computational implementations, and
point out issues arising from attempts at giving definitions of chaos that are
not entropy-based.
PMID- 26428572
TI - The joy of transient chaos.
AB - We intend to show that transient chaos is a very appealing, but still not widely
appreciated, subfield of nonlinear dynamics. Besides flashing its basic
properties and giving a brief overview of the many applications, a few recent
transient-chaos-related subjects are introduced in some detail. These include the
dynamics of decision making, dispersion, and sedimentation of volcanic ash,
doubly transient chaos of undriven autonomous mechanical systems, and a dynamical
systems approach to energy absorption or explosion.
PMID- 26428573
TI - Beyond the KdV: Post-explosion development.
AB - Several threads of the last 25 years' developments in nonlinear wave theory that
stem from the classical Korteweg-de Vries (KdV) equation are surveyed. The focus
is on various generalizations of the KdV equation which include higher-order
nonlinearity, large-scale dispersion, and a non-local integral dispersion. We
also discuss how relatively simple models can capture strongly nonlinear dynamics
and how various modifications of the KdV equation lead to qualitatively new, non
trivial solutions and regimes of evolution observable in the laboratory and in
nature. As the main physical example, we choose internal gravity waves in the
ocean for which all these models are applicable and have genuine importance. We
also briefly outline the authors' view of the future development of the chosen
lines of nonlinear wave theory.
PMID- 26428575
TI - Granular chaos and mixing: Whirled in a grain of sand.
AB - In this paper, we overview examples of chaos in granular flows. We begin by
reviewing several remarkable behaviors that have intrigued researchers over the
past few decades, and we then focus on three areas in which chaos plays an
intrinsic role in granular behavior. First, we discuss pattern formation in
vibrated beds, which we show is a direct result of chaotic scattering combined
with dynamical dissipation. Next, we consider stick-slip motion, which involves
chaotic scattering on the micro-scale, and which results in complex and as yet
unexplained peculiarities on the macro-scale. Finally, we examine granular
mixing, which we show combines micro-scale chaotic scattering and macro-scale
stick-slip motion into behaviors that are well described by dynamical systems
tools, such as iterative mappings.
PMID- 26428574
TI - Networkcontrology.
AB - An increasing number of complex systems are now modeled as networks of coupled
dynamical entities. Nonlinearity and high-dimensionality are hallmarks of the
dynamics of such networks but have generally been regarded as obstacles to
control. Here, I discuss recent advances on mathematical and computational
approaches to control high-dimensional nonlinear network dynamics under general
constraints on the admissible interventions. I also discuss the potential of
network control to address pressing scientific problems in various disciplines.
PMID- 26428576
TI - Advanced treatment of biologically pretreated coal gasification wastewater by a
novel integration of three-dimensional catalytic electro-Fenton and membrane
bioreactor.
AB - Laboratorial scale experiments were conducted to investigate a novel system three
dimensional catalytic electro-Fenton (3DCEF, catalyst of sewage sludge based
activated carbon which loaded Fe3O4) integrating with membrane bioreactor (3DCEF
MBR) on advanced treatment of biologically pretreated coal gasification
wastewater. The results indicated that 3DCEF-MBR represented high efficiencies in
eliminating COD and total organic carbon, giving the maximum removal efficiencies
of 80% and 75%, respectively. The integrated 3DCEF-MBR system significantly
reduced the transmembrane pressure, giving 35% lower than conventional MBR after
30 days operation. The enhanced hydroxyl radical oxidation and bacteria self
repair function were the mechanisms for 3DCEF-MBR performance. Therefore, the
integrated 3DCEF-MBR was expected to be the promising technology for advanced
treatment in engineering applications.
PMID- 26428577
TI - Reflectance confocal microscopy features of acral lentiginous melanoma: a
comparative study with acral nevi.
AB - BACKGROUND: Acral lentiginous melanoma (ALM) can be difficult to differentiate
from acral nevus. Reflectance confocal microscopy (RCM) is widely used for the
diagnosis of melanocytic tumours, but the RCM features of ALM and acral nevus
have not been described yet. OBJECTIVE: To determine the RCM features of ALM and
acral nevus, and their correlation with clinical and histological
characteristics. METHODS: Retrospective study of 17 cases of ALM and 26 acral
nevi. RESULTS: Pagetoid cells were present in all ALMs with a visible epidermis
and in three nevi. A proliferation of atypical melanocytes at the dermal
epidermal junction (DEJ) and/or in the dermis was visible in nine ALMs but not in
nevi. The histopathological examination of initial skin biopsies was unable to
diagnose ALM in four cases, differing from RCM that could identify malignant
tumour cells by exploring the whole lesions. CONCLUSION: Reflectance confocal
microscopy can help in the differentiation of ALM and acral nevus, and to guide
the biopsy.
PMID- 26428578
TI - Exploring the roles of basal transcription factor 3 in eukaryotic growth and
development.
AB - Basal transcription factor 3 (BTF3) has been reported to play a significant part
in the transcriptional regulation linking with eukaryotes growth and development.
Alteration in the BTF3 gene expression patterns or variation in their activities
adds to the explanation of different signaling pathways and regulatory networks.
Moreover, BTF3s often respond to numerous stresses, and subsequently they are
involved in regulation of various mechanisms. BTF3 proteins also function through
protein-protein contact, which can assist us to identify the multifaceted
processes of signaling and transcriptional regulation controlled by BTF3
proteins. In this review, we discuss current advances made in starting to explore
the roles of BTF3 transcription factors in eukaryotes especially in plant growth
and development.
PMID- 26428580
TI - Developing the Evidence Base for Interventions for International Child Health.
PMID- 26428579
TI - Nicotine inhibits hippocampal and striatal acetylcholinesterase activities, and
demonstrates dual action on adult neuronal proliferation and maturation.
AB - AIM: The present study investigated the effects of nicotine on
acetylcholinesterase (AChE) activities in the hippocampus and striatum; and on
immunoreactivity of certain neurogenic markers in the dentate gyrus (DG) of the
hippocampus. METHODS: Male rats were given daily subcutaneous injections of
nicotine at doses of 0.25, 2 or 4mg/kg body weight for 28 days. Animals were
euthanized by cervical dislocation at the end of administration. Brains were
excised and processed for histochemical demonstration of AChE and
immunohistochemical studies of Ki67, GFAP and NSE. RESULTS: There was significant
decrease (P<0.001) in AChE positive cells in the hippocampus and striatum
following 2 and 4mg/kg nicotine but not at 0.25mg/kg. Nicotine treatment at 0.25
and 4mg/kg significantly decrease (P<0.05) immunoreactivity of Ki67 and NSE in
DG. Contrastingly, 2mg/kg nicotine did not alter Ki67 immunoreactivity but rather
significantly increased (P<0.05) NSE immunoreactivity in DG compared to control.
CONCLUSION: This study suggests that nicotine may inhibit AChE activities in the
brain, thereby having a direct or indirect influence on prevention of central
acetylcholine degradation, as well as either improve or retard maturation adult
born neurons in DG, at different doses.
PMID- 26428581
TI - Non-typhoidal Salmonella infections in HIV-positive adults.
AB - Non-typhoidal salmonellae are important pathogens causing bacteraemia, especially
in immunocompromised patients, but there are limited data explicitly describing
the clinical characteristics and outcome in these individuals. Recurrent invasive
salmonellosis has been recognised as an AIDS-defining condition in HIV-positive
patients since the 1980s. Salmonella meningitis is an infrequent complication of
Salmonella sepsis, accounting for 0.8-6% of all cases of bacterial meningitis,
and is associated with a high mortality rate.
PMID- 26428582
TI - Indications for the use of bronchial thermoplasty in severe asthma.
AB - Approximately 5% of the ~3 million asthmatics in South Africa have severe asthma
that is associated with substantial morbidity, cost, absenteeism, preventable
mortality, and the requirement for costly chronic medication that may be
associated with significant adverse events. There is an unmet need for
alternative safer and more effective interventions for severe asthma. A recently
introduced option, bronchial thermoplasty (BT), imparts radiofrequency-generated
heat energy to the airways to cause regression of airway smooth muscle. The
effectiveness of this technique has been confirmed in randomised control trials
and is now endorsed by several international guidelines, including the Global
Initiative for Asthma (GINA) guideline, the British Asthma Guideline, and the UK
National Institute of Clinical Excellence (NICE) guideline. We recommend BT as a
potential therapeutic intervention for severe uncontrolled asthma, provided that
it is performed by an experienced pulmonologist at an accredited centre and done
within the broader context of appropriate management of the disease by doctors
experienced in treating difficult-to-control asthma.
PMID- 26428583
TI - Recommendations for the use of endoscopic lung volume reduction in South Africa:
Role in the treatment of emphysema.
AB - Emphysema is a very common cause of morbidity and mortality in South Africa (SA).
Therapeutic options in severe emphysema are limited. Endoscopic lung volume
reduction (ELVR) is increasingly being used internationally for the treatment of
advanced emphysema in a subset of patients with advanced disease, aiming to
obtain the same functional advantages as surgical lung volume reduction while
reducing risks and costs. In addition to endobronchial valves, ELVR using
endobronchial coils is now available in SA. The high cost of these interventions
underscores the need for careful patient selection to best identify those who may
or may not benefit from ELVR-related procedures. The Assembly on Interventional
Pulmonology of the South African Thoracic Society appointed a committee
comprising both local and international experts to extensively review all
relevant evidence and provide advice on the use of ELVR in SA based on published
evidence, expert opinion and local access to the various devices.
PMID- 26428584
TI - Impact of transthoracic echocardiography at district hospital level.
AB - BACKGROUND: The use of and demand for echocardiography (ECHO) has increased
worldwide. In developed countries, this has not translated into improved access
outside tertiary centres. Previous studies have favoured the appropriate use of
ECHO over its clinical impact, limiting generalisability to resource-constrained
settings. OBJECTIVES: To assess the impact of an ECHO service at district
hospital level in Cape Town, South Africa. METHODS: A prospective, cross
sectional study was performed. A total of 210 consecutive patients, referred to
the ECHO clinic over a 5-month period, were recruited. Transthoracic ECHO was
evaluated in terms of its indication, new information provided, correlation with
the referring doctor's diagnosis and subsequent management plan. Impact included
the escalation and de-escalation of treatment, as well as usefulness without a
change in management. RESULTS: The results show that 83.8% of the patients'
management was impacted on by echocardiography. Valvular lesions were the main
indication. The most frequent contribution was information provided towards the
diagnosis of heart failure and assessment after myocardial infarction. Of the
echocardiograms, 56.2% confirmed the referring doctor's diagnosis, yet were still
associated with a significant impact. The rational prescription of medication had
the major impetus, followed by de-escalation of therapy and screening patients to
determine referral to a tertiary facility. CONCLUSION: ECHO has a positive impact
on patient management outside tertiary settings, where the definition of impact
appears to be different. The value of a normal study, screening prior to upstream
referral and usefulness irrespective of change have been established. This should
alert policy makers against restriction of access to ECHO and promote training of
personnel in its use.
PMID- 26428585
TI - The wrong and wounding road: Paediatric polytrauma admitted to a level 1 trauma
intensive care unit over a 5-year period.
AB - BACKGROUND: Injury in childhood is a major cause of potentially preventable
morbidity and mortality. In order to implement effective preventive strategies,
epidemiological data on mechanisms of injury and outcome are essential.
OBJECTIVES: To assess the causation, severity of injury, morbidity and mortality
of paediatric trauma admitted to a level 1 trauma intensive care unit (TICU).
METHODS: Children were defined as being <16 years of age. The study covered the 5
year period January 2008-December 2012. Eligible patients were identified from a
prospective database maintained in the level 1 TICU at Inkosi Albert Luthuli
Central Hospital, Durban, South Africa. Data extracted were referral source,
mechanism of injury, age and gender distribution, injury severity score (ISS),
anatomical distribution of injury and mortality. RESULTS: A total of 181 patients
admitted during the study period accounted for 15.9% of all admissions. There
were 84 females (46.4%) and 97 males (53.6%), with a median age of 7 years
(interquartile range (IQR) 4-10). Sources of admission were directly from the
scene in 38 cases (21.0%), from a primary healthcare facility in 47 (26.0%), from
a regional hospital in 56 (31.0%) and from a tertiary facility in 40 (22.0%).
Mortality rates according to location of transfer were regional hospital 8 deaths
(30.8%), tertiary facility 7 (26.9%), primary health clinic 7 (26.9%), and from
the scene 4 (15.4%). Mechanisms of injury were pedestrian-motor vehicle collision
(PMVC) in 105 cases (58.0%), motor vehicle passenger in 38 (21.0%), non-vehicular
blunt trauma in 18 (10.0%), gunshot wounds (GSWs) in 12 (6.6%), stab wounds in 6
(3.3%), bull goring in 1 (0.5%) and bicycle accident 1 (0.5%). The median ISS for
all admissions was 25 (IQR 16-38). ISSs were >25 in 98 patients (54.1%), 16-25 in
51 (28.2%), 9-15 in 9 (4.9%) and <9 in 13 (7.2%); 61.9% of patients had head
injuries, 48.1% injuries to the extremities, 41.4% abdominal trauma, 40.3%
thoracic trauma, 20.4% external soft-tissue trauma, 9.9% cervical injury and 9.4%
facial trauma. There were 26 deaths (14.4%), of which PMVCs accounted for 16
(61.5%), motor vehicle passengers for 7 (26.9%), blunt trauma for 2 (7.7%) and
GSWs for 1 (3.8%). The majority of deaths (92%) were of patients with an ISS>25.
Of the 26 patients who died, 88.4% had a head injury, 46.2% an extremity injury,
38.5% an external injury, 34.6% abdominal or chest injuries, 19.2% neck injury
and 11.5% facial injury. CONCLUSIONS: Motor vehicle-related injuries, especially
PMVCs, dominate severe paediatric trauma and there is an urgent need for more
road traffic education and stringent measures to decrease the incidence and
associated morbidity and mortality.
PMID- 26428586
TI - Interpersonal violence as a major contributor towards the skewed burden of trauma
in KwaZulu-Natal, South Africa.
AB - BACKGROUND: Trauma is one of the foremost causes of death worldwide, but there is
a paucity of data on demographics and injury patterns in developing countries.
OBJECTIVES: To quantify and describe the major trauma burden at a regional
hospital in KwaZulu-Natal (KZN), South Africa (SA), over a 5-year period.
METHODS: Ngwelezane Hospital is a large regional hospital in northern KZN. A
database is maintained of all major trauma patients admitted to the Emergency
Department (ED) resuscitation unit. Statistical analysis was performed to
quantify the burden of trauma and analyse trends in these data. RESULTS: Over a 5
year period, 3 735 major trauma patients were admitted to the ED resuscitation
unit. Analysis showed a male predominance, with a mean patient age of 28.6 years.
An average of 62 patients per month were admitted, the rate peaking over the
holiday seasons. Trauma secondary to interpersonal violence (IPV) predominated. A
disproportionately high level of pedestrian-motor vehicle collisions (PMVCs) in
relation to total road traffic collisions was noted. Blunt force trauma secondary
to motor vehicle collisions was the leading cause of death, while blunt force
trauma secondary to PMVC s carried the highest mortality rate. CONCLUSION: This
study highlights the high incidences of both IPV and PMVCs typical of trauma in
an SA setting. The demographics and injury patterns noted may be used to drive
public health interventions to address this burden of trauma.
PMID- 26428587
TI - The epidemiology of major incidents in the Western Cape Province, South Africa.
AB - BACKGROUND: Major incidents put pressure on any health system. There are
currently no studies describing the epidemiology of major incidents in South
Africa (SA). The lack of data makes planning for major incidents and exercising
of major incident plans difficult. OBJECTIVE: To describe the epidemiology of
major incidents in the Western Cape Province, SA. METHODS: A retrospective
analysis of the Western Cape Major Incident database was conducted for the period
1 December 2008-30 June 2014. Variables collected related to patient demographics
and incident details. Summary statistics were used to describe all variables.
RESULTS: Seven hundred and seventy-seven major incidents were reviewed (median
n=11 per month). Most major incidents occurred in the City of Cape Town (57.8%,
n=449), but the Central Karoo district had the highest incidence (11.97/10 000
population). Transport-related incidents occurred most frequently (94.0%, n=730).
Minibus taxis were involved in 312 major incidents (40.2%). There was no
significant difference between times of day when incidents occurred. A total of
8,732 patients were injured (median n=8 per incident); ten incidents involved 50
or more victims. Most patients were adults (80.0%, n=6 986) and male (51.0%,
n=4,455). Of 8,440 patients, 630 (7.5%) were severely injured. More than half of
the patients sustained minor injuries (54.6%, n=4,605). CONCLUSION: Major
incidents occurred more often than would have been expected compared with other
countries, with road traffic crashes the biggest contributor. A national database
will provide a better perspective of the burden of major incidents.
PMID- 26428588
TI - Epidemiology of acute spinal cord injuries in the Groote Schuur Hospital Acute
Spinal Cord Injury (GSH ASCI) Unit, Cape Town, South Africa, over the past 11
years.
AB - BACKGROUND: Spinal cord injury (SCI) is devastating to both patient and society,
with acute management and ongoing care being extremely expensive. Few
epidemiological data are available on SCIs in South Africa (SA). OBJECTIVES: To
identify the epidemiological profile of SCI patients at Groote Schuur Hospital
(GSH), Cape Town, SA, and identify seasonal trends and peak periods. As the
majority of the injuries are preventable, these data are important to develop
prevention strategies. METHODS: A retrospective review of prospectively collected
data was conducted on all patients admitted to the Acute Spinal Cord Injury
(ASCI) Unit at GSH from 1 April 2003 to 31 March 2014. All cases registered on a
prospectively maintained database were included in the study. RESULTS: The total
number of patients admitted to the ASCI Unit was 2,042, with an average of 185
admissions per year. The male/female ratio was 5.25:1. The 21-30-year-old age
category was the largest, comprising 33.5% of the patients. The most prevalent
cause of injury was motor vehicle accidents (44.6%), followed by violence-related
injuries (27.2%). Thirty-two point two per cent of patients needed ventilatory
support, and 91.5% of mechanically ventilated patients were successfully weaned.
December was the busiest month in the unit. In patients in whom neurological
deficit was incomplete, the average motor function improvement was 16.0%.
CONCLUSIONS: Data capturing and analysis of SCIs should be encouraged in SA to
guide management and prevention strategies, and to optimise outcomes. This study
establishes the ASCI Unit at GSH to be one of the key role players in acute SCI
management in SA.
PMID- 26428589
TI - Meeting national response time targets for priority 1 incidents in an urban
emergency medical services system in South Africa: More ambulances won't help.
AB - BACKGROUND: Response time is viewed as a key performance indicator in most
emergency medical services (EMS) systems. OBJECTIVE: To determine the effect of
increased emergency vehicle numbers on response time performance for priority 1
incidents in an urban EMS system in Cape Town, South Africa, using discrete-event
computer simulation. METHOD: A simulation model was created, based on input data
from part of the EMS operations. Two different versions of the model were used,
one with primary response vehicles and ambulances and one with only ambulances.
In both cases the models were run in seven different scenarios. The first
scenario used the actual number of emergency vehicles in the real system, and in
each subsequent scenario vehicle numbers were increased by adding the baseline
number to the cumulative total. RESULTS: The model using only ambulances had
shorter response times and a greater number of responses meeting national
response time targets than models using primary response vehicles and ambulances.
In both cases an improvement in response times and the number of responses
meeting national response time targets was observed with the first incremental
addition of vehicles. After this the improvements rapidly diminished and
eventually became negligible with each successive increase in vehicle numbers.
The national response time target for urban areas was never met, even with a
seven-fold increase in vehicle numbers. CONCLUSION: The addition of emergency
vehicles to an urban EMS system improves response times in priority 1 incidents,
but alone is not capable of the magnitude of response time improvement needed to
meet the national response time targets.
PMID- 26428590
TI - The appropriateness of emergency medical service responses in the eThekwini
district of KwaZulu-Natal, South Africa.
AB - INTRODUCTION: Emergency medical services (EMS) are sometimes required to respond
to cases that are later found not to be emergencies, resulting in high levels of
inappropriate responses. This study evaluated the extent to which this occurs.
METHODS: All cases dispatched over 72 hours by the eThekwini EMS in Durban,
South Africa, were prospectively enrolled in a quantitative descriptive study.
Vehicle control forms containing dispatch data were matched and compared with
patient report forms containing epidemiological and clinical data to describe the
nature and extent of inappropriate responses based on patient need. Data were
subjected to simple descriptive analysis, correlations and chi2 testing. RESULTS:
A total of 1 385 cases met the study inclusion criteria. Marked variations
existed between dispatch and on-scene priority settings, most notably in the
highest priority 'red-code' category, which constituted >56% of cases dispatched
yet accounted for <2% at the scene (p<0.001). Conversely, >80% of 'red-code'
dispatches required a lower priority response. When comparing resource allocation
according to patient interventional needs, >58% of cases required either no
intervention or transport only and almost 36% required basic life support
intervention only (p<0.001). Moreover, <12% of advanced life support dispatches
were for patients found to be 'red code' at the scene. CONCLUSION: There is a
significant mismatch between the dispatch of EMS resources and actual patient
need in the eThekwini district, with significantly high levels of inappropriate
emergency responses.
PMID- 26428591
TI - A 10-year review of fatal community assault cases at a regional forensic
pathology facility in Cape Town, South Africa.
AB - BACKGROUND: An increase in autopsied community assault (CA) fatalities was
observed at the Tygerberg Forensic Pathology Services (FPS), Cape Town, South
Africa (SA). There is a paucity of information on the incidence and prevalence of
these cases in SA. OBJECTIVES: To determine the patterns and trends of injuries
sustained in so-called CA fatalities. METHODS: A retrospective and descriptive
study was conducted. Fatal CA cases admitted to the Tygerberg FPS over the 10
year period 1 January 2003-31 December 2012 were reviewed. Data were collected
from autopsy/postmortem reports, contemporaneous notes, attached hospital
records, the South African Police Services (SAPS) 180 form (completed by the SAPS
representative) and other FPS documentation. RESULTS: A total of 424 cases of
fatal CA were seen during the study period, with an annual increase between 2003
and 2007 and a second peak in 2012. The cause of death in most cases was multiple
injuries (42.0%), with blunt-force trauma being the basis of most injuries
sustained. The area with the greatest burden of injury was the township of
Mfuleni (73 CA deaths per 100,000 population). There was a predominance of males,
with only one female fatality recorded. CONCLUSION: Adequate policing in
prevalent areas is essential to address unnecessary loss of life and the burden
imposed by these cases on the criminal justice system and healthcare services.
PMID- 26428592
TI - A review of primary and secondary burn services in the Western Cape, South
Africa.
AB - BACKGROUND: In 2011, the Department of Health of the Western Cape Province, South
Africa, requested a review of current burn services in the province, with a view
to formulating a more efficient and cost-effective service. This article
considers the findings of the review and presents strategies to improve delivery
of appropriate burn care at primary and secondary levels. METHODS: Surveys were
conducted at eight rural and urban hospitals, two outreach workshops on burn
care, four regional hospitals and at least 60 clinics in Cape Town and in the
Western Cape as far as Ladismith. A survey on community management of paediatric
burns was also included in the study. RESULTS: The incidence of burns was highest
in the winter months, more than half of those affected were children, and the
majority of burns were scalds from hot liquids. Most burn injuries managed at
primary level were minor, with 75% of patients treated by nurse practitioners and
discharged. The four regional secondary hospitals managed the majority of
moderate to severe burns. There is room for improvement in terms of treatment
facilities and consumables at all levels, regional hospitals being particularly
restricted in terms of outdated equipment, a shortage of intensive care unit
beds, and difficulties in transferring patients with major burns to a burns unit
when indicated. CONCLUSION: The community management of paediatric burns was
satisfactory, although considerable delays in transfer and insufficient pain
control hampered appropriate care. A great need for ongoing education at all
levels was identified. Ten strategies are presented that could, if implemented,
lead to tangible improvements in the management of burn patients at primary and
secondary levels in the Western Cape.
PMID- 26428593
TI - Self-expanding metal stent placement for oesophageal cancer without fluoroscopy
is safe and effective.
AB - BACKGROUND: Self-expanding metal stents (SEMS) are widely used to palliate
patients with oesophageal cancer. Placement is usually done under endoscopic and
fluoroscopic guidance. We have developed an exclusively endoscopic technique to
deploy these stents. This article documents the technique and periprocedural
experience. PATIENTS AND METHODS: All patients who had SEMS placement for
oesophageal cancer at Grey's Hospital, Pietermaritzburg, South Africa, over a 5
year period (2007-2011) were reviewed. Stenting was performed without
radiological guidance using the technique documented in this article. At
endoscopy, the oesophageal lesion was identified, dilated over a guidewire if
necessary, and a partially covered stent was passed over the wire and positioned
and deployed under direct vision. Data were captured from completed procedure
forms and included demographics, tumour length, the presence of fistulas, stent
size and immediate complications. RESULTS: A total of 480 SEMS were inserted,
involving 453 patients, of whom 43 required repeat stenting. There were 185
female patients (40.8%) and 268 male patients (59.2%). The mean age was 60 years
(range 38 - 101). There were 432 black patients (95.4%), 15 white patients (3.3%)
and 6 Indian patients (1.3%). The reasons for palliative stenting were
distributed as follows: age>70 years n=95 patients, tumour>8 cm n=142, tracheo
oesophageal fistula (TOF) n=29, and unspecified n=170. One patient refused
surgery, and one stent was placed for a post-oesophagectomy leak. Repeat stenting
was for stent migration (n=15), tumour overgrowth (n=26) and a blocked stent and
a stricture (n=1 each). Complications were recorded in six cases (1.3%):
iatrogenic TOF (n=2), false tracts (n=3) and perforation (n=1). All six were
nevertheless successfully stented. There was no periprocedural mortality.
CONCLUSION: The endoscopic placement technique described is a viable and safe
option with a low periprocedural complication rate. It is of particular use in
situations of restricted access to fluoroscopic guidance.
PMID- 26428594
TI - Pulmonary tuberculosis in a South African regional emergency centre: Can
infection control be improved to lower the risk of nosocomial transmission?
AB - BACKGROUND: George Regional Hospital (GRH) is a 272-bed regional referral
hospital for the Eden and Central Karoo districts, Western Cape Province, South
Africa. The perception among emergency centre (EC) staff is that a high burden of
tuberculosis (TB) is being diagnosed and that infection control procedures are
currently lacking, leading to a high risk of nosocomial transmission. OBJECTIVES:
To establish the burden of pulmonary TB (PTB) presenting to GRH via the EC and
audit current infection prevention and control practices, to quantify the risk of
transmission of PTB in the EC and to establish whether infection control measures
are inadequate. METHODS: An audit of infection control based on the Centers for
Disease Control audit tool for TB, analysis of results, and implementation of new
infection control measures including a new standard operating procedure based on
a set of triage criteria. RESULTS: Implementation of new triage criteria and a
standard operating procedure led to the longest length of stay of a patient with
suspected TB in the EC being reduced by 40% (from 142 hours to 84 hours). The
average time between seeing a doctor and leaving the EC for patients with
suspected TB was reduced by 20% (from 20 hours 40 minutes to 16 hours 45
minutes). CONCLUSION: Simple measures implemented in the EC led to a significant
reduction in the time patients with suspected or confirmed TB spent in the EC.
This should lead to a reduced risk of nosocomial transmission of TB to both staff
and patients.
PMID- 26428595
TI - Prevalence of breast tuberculosis: Retrospective analysis of 65 patients
attending a tertiary hospital in Durban, South Africa.
AB - BACKGROUND: Breast tuberculosis (BTB) is uncommon, but not rare. Knowledge of the
ways in which it can present can prevent unnecessary invasive procedures and
delay in diagnosis. OBJECTIVES: To describe the clinical and radiological
findings in patients with BTB, including evaluation of current treatment methods.
METHODS: We retrospectively analysed 65 patients diagnosed with BTB at Addington
and King Edward VIII hospitals, Durban, South Africa, between 2000 and 2013.
Demographic, clinical and radiological findings and treatment outcomes were
noted. RESULTS: A total of 11,092 patients underwent breast investigations
between 2009 and 2013, with a prevalence of BTB for the period of 0.3% (30
patients). Of the 65 patients diagnosed between 2000 and 2013, 64 were female
(98.5%) and one was male (1.5%). The age range was 23-69 years (mean 38.5). The
most common mammographic pattern was density (39.4%) and the least common a mass
(6.1%). Isolated axillary lymphadenitis was found in 12.1%. Abscess was the
commonest ultrasound pattern (39.0%). Of the 47 patients with a known history of
pulmonary tuberculosis (TB), 68.1% (n=32) did not have radiological evidence of
previous or concurrent pulmonary TB, nor was there evidence of TB elsewhere. Of
47 patients with known HIV status, 34 were HIV-positive. Fine-needle aspiration
cytology had sensitivity of only 28% compared with 94% for histology. Of those
treated, 72.7% obtained full resolution following 9 months of TB treatment; 25.0%
did not complete treatment, and 2.3% (n=1) died while on treatment. Follow-up
data on relapse rates after treatment completion and disease resolution are
scanty. CONCLUSION: Understanding and being aware of the various presentations of
BTB make it possible to treat most patients successfully.
PMID- 26428596
TI - Prenatal BoBsTM in the cytogenetic analysis of products of spontaneous
miscarriage.
AB - BACKGROUND: Fifty percent of spontaneous miscarriages (SMs) are attributed to
chromosomal abnormalities. Cytogenetic analysis is an important tool for patient
counselling and assessment of the risk of recurrence in future pregnancies.
Conventional karyotyping has been the gold standard for chromosomal investigation
of products of conception (POC), but it has limitations due to sample maceration,
culture failure and maternal cell contamination. Molecular cytogenetic approaches
have therefore been developed and found valuable in the cytogenetic investigation
of these samples. The Prenatal BoBsTM and KaryoLite BoBsTM, based on the newly
developed BACs-on-BeadsTM technology, have been described as reliable tests for
rapid detection of aneuploidies in prenatal and POC samples, respectively.
OBJECTIVE: To describe our clinical experience of routine screening of POC
samples with Prenatal BoBsTM, the test used by our laboratory in France. METHODS:
Seventeen samples collected at the University Hospital of Sidi Bel Abbes (Western
Algeria) and a further 60 from the University Hospital of Clermont-Ferrand
(France) were analysed (19 chorionic villi from products of curettage, 12
placentas, 9 amniotic cells and 37 biopsy specimens). All were screened for the
frequent aneuploidies (chromosomes 13, 18, 21, X and Y) in addition to nine
microdeletion/microduplication syndrome regions by Prenatal BoBsTM. Standard
karyotyping was performed on 51 samples, but failed in 38 cases. RESULTS:
Prenatal BoBsTM identified one trisomy 21 and one deletion of 17p13.3.
Furthermore, it provided a conclusive result in cases of culture failure (n=38)
and in samples with macerated tissue (n=19). The overall failure rate was 11.4%.
CONCLUSIONS: Prenatal BoBsTM is a promising technology that represents a fast,
sensitive and robust alternative to routine screening for chromosomal abnormality
in products of SM. Furthermore, it overcomes the limitations of conventional
karyotyping and current molecular cytogenetic techniques.
PMID- 26428597
TI - Geography should be taught at medical school.
PMID- 26428598
TI - Compressed sensing of ECG signal for wireless system with new fast iterative
method.
AB - Recent experiments in wireless body area network (WBAN) show that compressive
sensing (CS) is a promising tool to compress the Electrocardiogram signal ECG
signal. The performance of CS is based on algorithms use to reconstruct exactly
or approximately the original signal. In this paper, we present two methods work
with absence and presence of noise, these methods are Least Support Orthogonal
Matching Pursuit (LS-OMP) and Least Support Denoising-Orthogonal Matching Pursuit
(LSD-OMP). The algorithms achieve correct support recovery without requiring
sparsity knowledge. We derive an improved restricted isometry property (RIP)
based conditions over the best known results. The basic procedures are done by
observational and analytical of a different Electrocardiogram signal downloaded
them from PhysioBankATM. Experimental results show that significant performance
in term of reconstruction quality and compression rate can be obtained by these
two new proposed algorithms, and help the specialist gathering the necessary
information from the patient in less time if we use Magnetic Resonance Imaging
(MRI) application, or reconstructed the patient data after sending it through the
network.
PMID- 26428599
TI - MioLab, a rat cardiac contractile force simulator: Applications to teaching
cardiac cell physiology and biophysics.
AB - INTRODUCTION: Understanding the basic concepts of physiology and biophysics of
cardiac cells can be improved by virtual experiments that illustrate the complex
excitation-contraction coupling process in cardiac cells. The aim of this study
is to propose a rat cardiac myocyte simulator, with which calcium dynamics in
excitation-contraction coupling of an isolated cell can be observed. This model
has been used in the course "Mathematical Modeling and Simulation of Biological
Systems". In this paper we present the didactic utility of the simulator
MioLab((r)). METHODS: The simulator enables virtual experiments that can help
studying inhibitors and activators in the sarcoplasmic reticulum sodium-calcium
exchanger, thus corroborating a better understanding of the effects of
medications, which are used to treat arrhythmias, on these compartments. The
graphical interfaces were developed not only to facilitate the use of the
simulator, but also to promote a constructive learning on the subject, since
there are animations and videos for each stage of the simulation. The
effectiveness of the simulator was tested by a group of graduate students.
RESULTS: Some examples of simulations were presented in order to describe the
overall structure of the simulator. Part of these virtual experiments became an
activity for Biomedical Engineering graduate students, who evaluated the
simulator based on its didactic quality. As a result, students answered a
questionnaire on the usability and functionality of the simulator as a teaching
tool. All students performed the proposed activities and classified the simulator
as an optimal or good learning tool. In their written questions, students
indicated as negative characteristics some problems with visualizing graphs; as
positive characteristics, they indicated the simulator's didactic function,
especially tutorials and videos on the topic of this study. CONCLUSIONS: The
results show that the simulator complements the study of the physiology and
biophysics of the cardiac cell.
PMID- 26428600
TI - Congenital Mirror Movements in a 7-Year-Old Boy.
PMID- 26428601
TI - [Solitary tuberculous lesion of the right frontal lobe mimicking a malignant
tumor].
PMID- 26428602
TI - Update on the epidemiology, diagnosis, and treatment of leprosy.
AB - Leprosy is an infectious disease that has now been reported for more than 2000
years. The leprosy elimination goal set by the World Health Organization (WHO),
i.e. a global prevalence rate <1 patient per 10,000 population, was achieved in
the year 2000, but more than 200,000 new case patients are still reported each
year, particularly in India, Brazil, and Indonesia. Leprosy is a specific
infection: (i) it is a chronic infection primarily affecting the skin and
peripheral nerves, (ii) Mycobacterium leprae is one of the last bacterial species
of medical interest that cannot be cultured in vitro (mainly because of its
reductive genome evolution), and (iii) transmission and pathophysiological data
is still limited. The various presentations of the disease (Ridley-Jopling and
WHO classifications) are correlated with the patient's immune response, bacillary
load, and by the delay before diagnosis. Multidrug therapy (dapsone, rifampicin,
with or without clofazimine) has been recommended since 1982 as the standard
treatment of leprosy; 6 months for patients presenting with paucibacillary
leprosy and 12 months for patients presenting with multibacillary leprosy. The
worldwide use of leprosy drugs started in the 1980s and their free access since
1995 contributed to the drastic decline in the number of new case patients.
Resistant strains are however emerging despite the use of multidrug therapy;
identifying and monitoring resistance is still necessary.
PMID- 26428603
TI - Biodegradation and detoxification of textile dye Disperse Red 54 by Brevibacillus
laterosporus and determination of its metabolic fate.
AB - Bioremediation is one of the milestones achieved by the biotechnological
innovations. It is generating superior results in waste management such as
removal of textile dyes, which are considered xenobiotic compounds and
recalcitrant to biodegradation. In the present bioremedial approach,
Brevibacillus laterosporus was used as an effective microbial tool to decolorize
disperse dye Disperse Red 54 (DR54). Under optimized conditions (pH 7, 40 degrees
C), B. laterosporus led to 100% decolorization of DR54 (at 50 mg L(-1)) within 48
h. Yeast extract and peptone, supplemented in medium enhanced the decolorization
efficiency of the bacterium. During the decolorization process, activities of
enzymes responsible for decolorization, such as tyrosinase, veratryl alcohol
oxidase and NADH--DCIP reductase were induced by 1.32-, 1.51- and 4.37-fold,
respectively. The completely different chromatographic/spectroscopic spectrum of
metabolites obtained after decolorization confirmed the biodegradation of DR54 as
showed by High pressure liquid chromatography, High pressure thin layer
chromatography and Fourier transform infrared spectroscopy. Gas chromatography
Mass spectroscopy studies suggested the parent dye was biodegraded into simple
final product, N-(1lambda(3)-chlorinin-2-yl)acetamide. Phytotoxicity study
suggested that the metabolites obtained after biodegradation of DR54 were non
toxic as compared to the untreated dye signifying the detoxification of the DR54
by B. laterosporus.
PMID- 26428604
TI - DISTINGUISHING POLYPOIDAL CHOROIDAL VASCULOPATHY FROM TYPICAL NEOVASCULAR AGE
RELATED MACULAR DEGENERATION BASED ON SPECTRAL DOMAIN OPTICAL COHERENCE
TOMOGRAPHY.
AB - PURPOSE: To investigate the sensitivity and specificity of spectral domain
optical coherence tomography in distinguishing polypoidal choroidal vasculopathy
(PCV) from typical neovascular age-related macular degeneration (nAMD). METHODS:
One hundred and eighty-eight eyes in 156 patients with active PCV or typical nAMD
were enrolled prospectively. Three spectral domain optical coherence tomography
manifestations, pigment epithelium detachment, double-layer sign, and thumb-like
polyps were estimated in all the eyes. A diagnostic test to differentiate PCV
from nAMD based on spectral domain optical coherence tomography was performed.
Furthermore, the sensitivity and specificity was validated in a retrospective
series of patients. RESULTS: Pigment epithelium detachment, double-layer sign,
and thumb-like polyps were more common in PCV eyes than in nAMD eyes. When the
cutoff point was set as at least 2 positive signs out of 3 in the diagnostic
test, the sensitivity was 89.4% and specificity was 85.3%. The results of the
validation test further confirmed the strategy, with satisfying sensitivity
(87.5%) and specificity (86.2%). CONCLUSION: Spectral domain optical coherence
tomography is sensitive and specific in distinguishing PCV from nAMD. From these
results, the presence of at least two out three signs (pigment epithelium
detachment, double-layer sign, and thumb-like polyps) indicates a positive test
and is therefore suggested to be the screening strategy for PCV.
PMID- 26428605
TI - SURGICAL OUTCOME OF LATE IN-THE-BAG INTRAOCULAR LENS DISLOCATION TREATED WITH
PARS PLANA VITRECTOMY.
AB - PURPOSE: To present the visual outcome and postoperative complications of pars
plana vitrectomy and intraocular lenses (IOL) removal with or without IOL
exchange of late in-the-bag IOL dislocation after uneventful cataract surgery.
METHODS: Retrospective analysis of a consecutive series of 83 eyes with late in
the-bag dislocated IOL treated with pars plana vitrectomy and anterior chamber
IOL (25 eyes), transscleral suture-fixated posterior chamber IOL (38 eyes), or
aphakia (20 eyes). RESULTS: High myopia was the major predisposing factor (40%).
The interval between cataract surgery and the dislocation was 10.9 years. The
complication rate after the second surgery was 43%; being transient hypotony
(19%) and hypertension (15%) the most frequent. Postoperative best-corrected
visual acuity improvement was statistically significant (P < 0.001), with a mean
of 3 Snellen lines. This improvement was also significant in 2 subgroups,
patients with sutured posterior chamber IOL (20/80-20/40; P < 0.001) and in
patients with anterior chamber IOL (20/125-20/40; P < 0.001). However, best
corrected visual acuity did not improve in aphakic patients (20/63-20/63; P =
0.13). Postoperative astigmatism increased significantly (P < 0.001), with a mean
of -1 D. Mean follow-up was 24 months. CONCLUSION: The major predisposing factor
for late in-the-bag IOL dislocation is myopia. Despite a complication rate of
43%, mostly minor and transient, IOL exchange surgery is an effective procedure
with a good visual outcome (mean 3 Snellen lines improvement). There were no
statistically significant differences in the final best-corrected visual acuity
or complication rate between anterior chamber IOL and sutured posterior chamber
IOL, thus, both surgical techniques may be considered to treat this condition.
PMID- 26428606
TI - SOCIETAL COSTS ASSOCIATED WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN
THE UNITED STATES.
AB - PURPOSE: The purpose of this study was to use a cross-sectional prevalence-based
health care economic survey to ascertain the annual, incremental, societal
ophthalmic costs associated with neovascular age-related macular degeneration.
METHODS: Consecutive patients (n = 200) with neovascular age-related macular
degeneration were studied. A Control Cohort included patients with good (20/20
20/25) vision, while Study Cohort vision levels included Subcohort 1: 20/30 to
20/50, Subcohort 2: 20/60 to 20/100, Subcohort 3: 20/200 to 20/400, and Subcohort
4: 20/800 to no light perception. An interviewer-administered, standardized,
written survey assessed 1) direct ophthalmic medical, 2) direct nonophthalmic
medical, 3) direct nonmedical, and 4) indirect medical costs accrued due solely
to neovascular age-related macular degeneration. RESULTS: The mean annual
societal cost for the Control Cohort was $6,116 and for the Study Cohort averaged
$39,910 (P < 0.001). Study Subcohort 1 costs averaged $20,339, while Subcohort 4
costs averaged $82,984. Direct ophthalmic medical costs comprised 17.9% of Study
Cohort societal ophthalmic costs, versus 74.1% of Control Cohort societal
ophthalmic costs (P < 0.001) and 10.4% of 20/800 to no light perception subcohort
costs. Direct nonmedical costs, primarily caregiver, comprised 67.1% of Study
Cohort societal ophthalmic costs, versus 21.3% ($1,302/$6,116) of Control Cohort
costs (P < 0.001) and 74.1% of 20/800 to no light perception subcohort costs.
CONCLUSION: Total societal ophthalmic costs associated with neovascular age
related macular degeneration dramatically increase as vision in the better-seeing
eye decreases.
PMID- 26428607
TI - IMAGE ARTIFACTS IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB - PURPOSE: To describe image artifacts of optical coherence tomography (OCT)
angiography and their underlying causative mechanisms. To establish a common
vocabulary for the artifacts observed. METHODS: The methods by which OCT
angiography images are acquired, generated, and displayed are reviewed as are the
mechanisms by which each or all of these methods can produce extraneous image
information. A common set of terminology is proposed and used. RESULTS: Optical
coherence tomography angiography uses motion contrast to image blood flow and
thereby images the vasculature without the need for a contrast agent. Artifacts
are very common and can arise from the OCT image acquisition, intrinsic
characteristics of the eye, eye motion, image processing, and display strategies.
Optical coherence tomography image acquisition for angiography takes more time
than simple structural scans and necessitates trade-offs in flow resolution, scan
quality, and speed. An important set of artifacts are projection artifacts in
which images of blood vessels seem at erroneous locations. Image processing used
for OCT angiography can alter vascular appearance through segmentation defects,
and because of image display strategies can give false impressions of the density
and location of vessels. Eye motion leads to discontinuities in displayed data.
Optical coherence tomography angiography artifacts can be detected by interactive
evaluation of the images. CONCLUSION: Image artifacts are common and can lead to
incorrect interpretations of OCT angiography images. Because of the quantity of
data available and the potential for artifacts, physician interaction in viewing
the image data will be required, much like what happens in modern radiology
practice.
PMID- 26428608
TI - VOLUME-RENDERED ANGIOGRAPHIC AND STRUCTURAL OPTICAL COHERENCE TOMOGRAPHY.
AB - PURPOSE: To demonstrate combined and integrated volume rendering of the retinal
vasculature and selected structural abnormalities information derived from
optical coherence tomography. METHODS: The eyes were scanned using optical
coherence tomography using split-spectrum amplitude-decorrelation techniques to
derive flow information. Various sublayers could be color coded as needed. The
corresponding structural optical coherence tomography information was segmented
for salient anatomic structures of interest, such as areas of edema fluid or
intraretinal lipid deposits. The angiographic and structural data were integrated
on a plane-by-plane basis and used to create volume-rendered images. The combined
volume-rendered angiographic and structural optical coherence tomography data
could be rotated about three different axes for evaluation. RESULTS:
Representative images from the eyes with diabetic macular edema, Type 1 macular
telangiectasis, choroidal neovascularization, and retinal veno-occlusive disease
are shown. The interrelationships between areas of cystoid fluid accumulation or
intraretinal lipid accumulation could be visualized. CONCLUSION: Although
structural and angiographic findings are typically shown in isolation, they can
be integrated into a merged data set that is amenable to volume rendering. Using
this new technique will allow investigation into the interrelationships between
vascular and structural abnormalities of the retina and choroid.
PMID- 26428609
TI - An Effective and Well Tolerated Strategy of Bladder Preservation Therapy in
Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer.
AB - To investigate bladder preservation therapy with a well tolerated strategy, 30
patients with bladder cancer underwent concomitant chemoradiotherapy with weekly
carboplatin. The 2-year overall survival was 75% for all patients, 43% and 95%
for patients without adjuvant chemotherapy or with adjuvant chemotherapy
separately. This strategy was well tolerated with 7% of Grade 3/4 late bladder
toxicity. BACKGROUND: The purpose of this study was to determine the feasibility
and clinical effectiveness of concurrent weekly carboplatin chemotherapy in
conjunction with definite radiation with or without adjuvant chemotherapy in the
treatment of muscle-invasive bladder cancer. PATIENTS AND METHODS: Between April
2010 and December 2013, 30 patients with muscle-invasive bladder cancer were
evaluated retrospectively in this study. Concurrent chemoradiotherapy (CCRT) with
weekly carboplatin was initiated. CCRT was followed by 2 courses of carboplatin
and gemcitabine limited to patients with Eastern Cooperative Oncology Group
performance status < 3 and age < 80 years. RESULTS: Thirty patients were treated
and all completed the CCRT protocol. Seven of 8 patients (88%) achieved a
pathological complete response (pCR) with CCRT alone, and 18 of 22 patients (82%)
treated with CCRT followed by adjuvant chemotherapy had a pCR. The median follow
up was 23.2 (range, 8.3-40.7) months. The median progression-free survival was
15.9 months for the CCRT group, and not sufficient to evaluate CCRT followed by
adjuvant chemotherapy. The median overall survival with CCRT was 18.8 months, and
had not yet been reached for CCRT with adjuvant chemotherapy. The protocol was
well tolerated for adverse events. CONCLUSION: Our study has shown that
concomitant chemotherapy using weekly carboplatin in the management of muscle
invasive bladder cancer is feasible and well tolerated, even in older patients.
Additional adjuvant chemotherapy with 2 cycles of carboplatin and gemcitabine
should be encouraged in physically fit patients. These results provide a basis
for randomized studies to compare this approach with conventional therapy for
patients who wish to preserve the bladder.
PMID- 26428610
TI - Clinical Disparities for Minorities and Foreign-Born Men With Undescended Versus
Descended Testicular Germ Cell Tumors.
AB - BACKGROUND: Few reports have been published regarding the outcomes of patients
who develop an undescended testicular malignancy (UTM). Our objective was to
analyze the sociodemographic and survival outcomes of patients with UTM and those
of with descended testicular malignancy (DTM). PATIENTS AND METHODS: All 17
registries constituting the Surveillance, Epidemiology, and End Results (SEER)
database were analyzed from 1988 to 2008. Patients with a descended or
undescended testis and a diagnosis of nonseminomatous or seminomatous testicular
cancer were identified. Descriptive statistical data and multivariate analysis
were used to identify the predictors of a UTM diagnosis. The primary outcomes
were overall and disease-specific survival. RESULTS: The study cohort included
10,159 men (95.3%) with DTM and 496 (4.7%) with UTM. Patients with UTM were more
likely to be older, married, and a minority or foreign born and to have seminoma,
a higher rate of node positivity, and a higher SEER stage compared with patients
with DTM. The median survival time for patients with UTM was longer than that for
patients with to DTM (83.1 vs. 72.5 months; P = .0001), although no difference
was found in cancer-specific mortality (P = .34). CONCLUSION: Patients with UTM
are more likely to be a minority or foreign born, highlighting a previously
unrecognized healthcare disparity that might represent a lack of diagnosis and
access to care.
PMID- 26428611
TI - Decompression of Odontogenic Cystic Lesions: Past, Present, and Future.
AB - Tumors and cystic lesions of the jawbones have been described since the late
1600s and it took another 200 years for classification systems to appear in the
medical, surgical, and dental literatures. In the late 1800s, Carl Partsch
introduced cystostomy, a method by which the cyst is converted into a pouch by
suturing its lining to the mucosa of the oral cavity. The purpose of this article
is to analyze the history, present, and future of cystic conditions of the jaws
and decompression, a modality of treatment that during the past few years has
regained the attention of oral and maxillofacial surgeons and pathologists owing
to its relative simplicity and effectiveness compared with other conservative
options.
PMID- 26428612
TI - Evaluation of Bone Healing After Osteotomies Prepared With Er:YAG Laser in
Contact and Noncontact Modes and Piezosurgery--An Animal Study.
AB - PURPOSE: To analyze the healing of bone tissue treated with Er:YAG laser contact
and noncontact modes of and piezosurgery in a rat model using triangular laser
profilometry. MATERIALS AND METHODS: Twenty-four 10-week-old adult male Wistar
rats were used in the study. Three osteotomies on the medial part of tibia were
performed in each animal, 1 in the right tibia and 2 in the left tibia. The
osteotomies were performed with a piezoelectric device set at maximal power and
the Er:YAG laser in contact mode (power, 7.5 W; pulse energy, 375 mJ; repetition
rate, 20 Hz; MSP mode) and noncontact mode (power, 7.5 W; pulse energy, 750 mJ;
repetition rate, 10 Hz; QSP mode) with a novel type of circular, digitally
controlled handpiece (x-Runner). After surgery, 6 animals were immediately
euthanized (group 1), and the others were euthanized after 1 week (group 2, n =
6), 2 weeks (group 3, n = 6), and 3 weeks (group 4, n = 6). Bone healing after
osteotomy was analyzed using a 3-dimensional laser scanning technique (ie, laser
triangulation profilometry). RESULTS: The volume reduction rates are similar for
all 3 techniques (0.2 to 0.25 mm(3) per week). Greater volume reduction of 0.25
mm3 per week was observed for the Er:YAG laser in noncontact mode (x-Runner).
After 3 weeks, almost complete healing of the prepared osteotomy was observed.
CONCLUSION: Within the limitations of this study, the osteotomies performed by
the Er:YAG laser in digitally controlled noncontact mode healed the fastest.
PMID- 26428613
TI - A Comparison of Torque Forces Used to Apply Intermaxillary Fixation Screws.
AB - PURPOSE: When establishing intermaxillary fixation (IMF) using bone screws,
fracture of a screw is a potential complication. This study was conducted to
investigate the forces that arise at bone screw insertion and to determine safety
margins between torque for manually tightened insertion and torque until breakage
for 3 different IMF screw systems, which could ultimately favor the use of 1 IMF
screw system based on decreased risk of complications. MATERIALS AND METHODS: IMF
screws were placed into porcine mandibles by 3 oral and maxillofacial surgeons.
The porcine mandibles were evaluated for cortical thickness and suitable
insertion sites by cone-beam computed tomography. Measurements of torque until
failure were performed on predrilled aluminum plates by the primary author. A
digital torque screwdriver measured 180 data points per second as continuous data
and recorded the measurements. RESULTS: Measurements indicated clear differences
in torsion forces between manually tightened insertions and torque until breakage
for all 3 IMF screw systems. No statistical difference in safety margins was
found among the IMF screw systems. CONCLUSIONS: Because no statistical
differences in safety margins were found among the IMF screw systems, this study
indicates that IMF screw selection should be based on other clinical factors,
such as ease of use or economic factors. Future prospective studies are necessary
to fully determine evidence-based criteria for IMF screw selection.
PMID- 26428614
TI - Severity of Soft Tissue Injury Within the Temporomandibular Joint Following
Condylar Fracture as Seen on Magnetic Resonance Imaging and Its Impact on Outcome
of Functional Management.
AB - PURPOSE: This study aimed to quantify articular soft tissue injury in condylar
fractures based on magnetic resonance imaging (MRI) findings and investigate the
impact of severity of articular soft tissue injury on the development of
postoperative complications after functional reduction of a condylar fracture.
PATIENTS AND METHODS: Fifty-four patients 18 to 60 years old with unilateral
undisplaced, deviated, or displaced condylar fractures were included in this
prospective study. Articular soft tissue within the temporomandibular joint (TMJ)
was evaluated using MRI within 7 days after the condylar fracture. Based on MRI
findings, such injuries were classified as grade I (hemarthrosis only), grade II
(hemarthrosis and disc displacement), grade III (hemarthrosis, disc displacement,
and capsular tear), or grade IV (disc perforation in association with grade I,
II, or III). All condylar fractures were treated conservatively using a
standardized functional reduction method and patients were followed for 1 year.
RESULTS: In 37 of 54 TMJs, MRI diagnosis of disc displacement was established,
and capsular tear was observed in 12 joints and hemarthrosis was present in 42
joints. Disc perforation was present in only 5 cases. Patients with hemarthrosis
alone (grade I) had the best outcome after functional reduction, whereas patients
with hemarthrosis and disc displacement (grade II) had comparatively poorer
results. Fifty percent of patients with grade II injury and 66.6% of patients
with associated capsular tear (grade III) had limited mouth opening and
restricted movement at the end of the follow-up period. One hundred percent of
patients with disc perforation (grade IV) had restricted joint movement and joint
noise. CONCLUSION: Results suggest that serious injury to the articular disc and
capsule of the TMJ is a major contributing factor toward the development of
complications after closed reduction of a condylar fracture.
PMID- 26428616
TI - The role of Amh signaling in teleost fish--Multiple functions not restricted to
the gonads.
AB - This review summarizes the important role of Anti-Mullerian hormone (Amh) during
gonad development in fishes. This Tgfbeta-domain bearing hormone was named after
one of its known functions, the induction of the regression of Mullerian ducts in
male mammalian embryos. Later in development it is involved in male and female
gonad differentiation and extragonadal expression has been reported in mammals as
well. Teleosts lack Mullerian ducts, but they have amh orthologous genes. amh
expression is reported from 21 fish species and possible regulatory interactions
with further factors like sex steroids and gonadotropic hormones are discussed.
The gonadotropin Fsh inhibits amh expression in all fish species studied. Sex
steroids show no consistent influence on amh expression. Amh is produced in male
Sertoli cells and female granulosa cells and inhibits germ cell proliferation and
differentiation as well as steroidogenesis in both sexes. Therefore, Amh might be
a central player in gonad development and a target of gonadotropic Fsh.
Furthermore, there is evidence that an Amh-type II receptor is involved in germ
cell regulation. Amh and its corresponding type II receptor are also present in
brain and pituitary, at least in some teleosts, indicating additional roles of
Amh effects in the brain-pituitary-gonadal axis. Unraveling Amh signaling is
important in stem cell research and for reproduction as well as for aquaculture
and in environmental science.
PMID- 26428615
TI - Six-month quality-of-life and functional status of acute respiratory distress
syndrome survivors compared to patients at risk: a population-based study.
AB - INTRODUCTION: The long-term attributable burden related to acute respiratory
distress syndrome (ARDS) is not fully investigated. The aim of this study is to
evaluate the quality of life (QOL) and functional status at 6 months after
hospitalization in patients at risk for ARDS who did and did not develop the
syndrome. METHOD: This is a population-based prospective cohort study of adult
patients from Olmsted County, Minnesota, with or at risk for ARDS hospitalized
from October 2008 to July 2011. The primary outcomes were changes in QOL and
functional status, measured through 12-Item Short Form Survey (SF-12) and Barthel
Index (BI) respectively, from baseline to 6 months, compared between survivors
who did and did not develop ARDS. RESULTS: Of 410 patients with or at risk for
ARDS, 98 had baseline surveys collected and 67 responded to a 6-month survey (26
ARDS, 41 non-ARDS). Both ARDS and non-ARDS groups had lower physical component of
SF-12 at baseline compared to general population (P < 0.001 for both). ARDS
patients had poorer baseline functional status compared to non-ARDS (mean BI 80
+/- 25 vs. 88 +/- 22, P = 0.03). No significant differences were observed for the
change between 6 months and baseline BI (delta 2.3 for ARDS vs. 2.0 for non-ARDS,
P = 0.5), or mental (delta 2.7 vs. 2.4, P = 0.9) or physical (delta -3 vs. -3.3,
P = 0.9) component of SF-12 between survivors with and without ARDS. CONCLUSION:
In this population-based study, decreased QOL and functional status 6 months
after hospitalization were largely explained by baseline condition, with similar
recovery in survivors who did and did not develop ARDS.
PMID- 26428617
TI - Extracellular signaling molecules to promote fracture healing and bone
regeneration.
AB - To date, the delivery of signaling molecules for bone regeneration has focused
primarily on factors that directly affect the bone formation pathways
(osteoinduction) or that serve to increase the number of bone forming progenitor
cells. The first commercialized growth factors approved for bone regeneration,
Bone Morphogenetic Protein 2 and 7 (BMP2 and BMP7), are direct inducers of
osteoblast differentiation. As well, newer generations of potential therapeutics
that target the Wnt signaling pathway are also direct osteoinducers. On the other
hand, some signaling molecules may play a role as mitogens and serve to increase
the number of bone producing cells or may increase vascularization. This is true
for factors such as Platelet Derived Growth Factor (PDGF) or Fibroblast Growth
Factor (FGF). Vascular Endothelial Growth Factor (VEGF) likely has a special
role. Not only does it induce new blood vessel formation, it also has direct
effects on osteoblasts through endothelial cell-based BMP production. In addition
to these pathways that classically have targeted bone production, there are also
opportunities to target other aspects of the bone healing process such as
inflammation, vascularization, and cell ingress to the fracture site. Bone
regeneration is highly complex with defined, yet overlapping stages of healing.
We will review established and novel extracellular signaling factors associated
with various stages of fracture healing that could be targeted to promote
enhanced bone regeneration. Importantly, multiple potential cell and tissues
could be targeted to enhance healing in addition to focusing solely on
osteoinductive therapeutics.
PMID- 26428618
TI - In vitro cardiac tissue models: Current status and future prospects.
AB - Cardiovascular disease is the leading cause of death worldwide. Achieving the
next phase of potential treatment strategies and better prognostic tools will
require a concerted effort from interdisciplinary fields. Biomaterials-based
cardiac tissue models are revolutionizing the area of preclinical research and
translational applications. The goal of in vitro cardiac tissue modeling is to
create physiological functional models of the human myocardium, which is a
difficult task due to the complex structure and function of the human heart. This
review describes the advances made in area of in vitro cardiac models using
biomaterials and bioinspired platforms. The field has progressed extensively in
the past decade, and we envision its applications in the areas of drug screening,
disease modeling, and precision medicine.
PMID- 26428620
TI - Race/ethnicity, and Americans' perceptions and experiences of over- and under-use
of care: a cross-sectional study.
AB - BACKGROUND: Despite widespread documentation of racial/ethnic disparities in care
(predominantly under-use of needed care), differences in population-wide
attitudes or experiences about under- or overuse (care where harms may outweigh
potential benefits) of care are not well understood. We examined whether
race/ethnicity is associated with perceptions or experiences of overuse or
underuse. METHODS: We conducted secondary analysis of a cross-sectional national
telephone survey of nationally representative sample of 1238 American adults;
57.9 % female, 75.4 % Non-Hispanic White, 11.8 % Non-Hispanic Black, 10.1 %
Hispanic. The main outcome measures are general perceptions and personal
experiences of overuse and underuse, including cost-related dimensions of each.
RESULTS: Bivariate results indicated that respondents of minority race/ethnicity
generally viewed both overuse and underuse as bigger problems than did Whites,
and reported more personal experiences of each. After adjustment, Hispanics were
less likely than Whites to report personal experiences of overuse (odds ratio
[OR] [95 % CI], 0.44 [0.23 to 0.86]), while Blacks and Others were more likely to
report cost-related overuse (ORs [95 % CIs], 4.16 [2.30 to 7.51]; 3.55 [1.52 to
8.28], respectively). Non-Hispanic Others more often reported doctors' protection
from overuse (OR [95 % CI], 3.69 [1.75 to 7.78]). General concerns with underuse
were more frequent among Blacks and Hispanics (ORs [95 % CIs], 3.07 [1.72 to
5.54]; 2.12 [1.24 to 3.61] respectively), while Others reported significantly
fewer concerns (OR [95 % CI], 0.43 [0.23 to 0.80]). CONCLUSIONS: Over- and
underuse of medical care are important problems for many Americans, and
experiences vary by race/ethnicity. Clinician communication and educational
campaigns about appropriateness of care may need tailoring for varying population
groups.
PMID- 26428619
TI - Engineered heart tissues and induced pluripotent stem cells: Macro- and
microstructures for disease modeling, drug screening, and translational studies.
AB - Engineered heart tissue has emerged as a personalized platform for drug
screening. With the advent of induced pluripotent stem cell (iPSC) technology,
patient-specific stem cells can be developed and expanded into an indefinite
source of cells. Subsequent developments in cardiovascular biology have led to
efficient differentiation of cardiomyocytes, the force-producing cells of the
heart. iPSC-derived cardiomyocytes (iPSC-CMs) have provided potentially limitless
quantities of well-characterized, healthy, and disease-specific CMs, which in
turn has enabled and driven the generation and scale-up of human physiological
and disease-relevant engineered heart tissues. The combined technologies of
engineered heart tissue and iPSC-CMs are being used to study diseases and to test
drugs, and in the process, have advanced the field of cardiovascular tissue
engineering into the field of precision medicine. In this review, we will discuss
current developments in engineered heart tissue, including iPSC-CMs as a novel
cell source. We examine new research directions that have improved the function
of engineered heart tissue by using mechanical or electrical conditioning or the
incorporation of non-cardiomyocyte stromal cells. Finally, we discuss how
engineered heart tissue can evolve into a powerful tool for therapeutic drug
testing.
PMID- 26428621
TI - Protein supplementation does not alter intramuscular anabolic signaling or
endocrine response after resistance exercise in trained men.
AB - The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling
pathway appears to be the primary regulator of muscle protein synthesis. A
variety of stimuli including resistance exercise, amino acids, and hormonal
signals activate mTORC1 signaling. The purpose of this study was to investigate
the effect of a protein supplement on mTORC1 signaling following a resistance
exercise protocol designed to promote elevations in circulating hormone
concentrations. We hypothesized that the protein supplement would augment the
intramuscular anabolic signaling response. Ten resistance-trained men (age, 24.7
+/- 3.4 years; weight, 90.1 +/- 11.3 kg; height, 176.0 +/- 4.9 cm) received
either a placebo or a supplement containing 20 g protein, 6 g carbohydrates, and
1 g fat after high-volume, short-rest lower-body resistance exercise. Blood
samples were obtained at baseline, immediately, 30 minutes, 1 hour, 2 hours, and
5 hours after exercise. Fine-needle muscle biopsies were completed at baseline, 1
hour, and 5 hours after exercise. Myoglobin, lactate dehydrogenase, and lactate
concentrations were significantly elevated after resistance exercise (P < .0001);
however, no differences were observed between trials. Resistance exercise also
elicited a significant insulin, growth hormone, and cortisol response (P < .01);
however, no differences were observed between trials for insulin-like growth
factor-1, insulin, testosterone, growth hormone, or cortisol. Intramuscular
anabolic signaling analysis revealed significant elevations in RPS6
phosphorylation after resistance exercise (P = .001); however, no differences
were observed between trials for signaling proteins including Akt, mTOR, p70S6k,
and RPS6. The endocrine response and phosphorylation status of signaling proteins
within the mTORC1 pathway did not appear to be altered by ingestion of supplement
after resistance exercise in resistance-trained men.
PMID- 26428622
TI - Neonatal thyroid-stimulating hormone level is influenced by neonatal, maternal,
and pregnancy factors.
AB - The percentage of newborns with a neonatal whole blood thyroid-stimulating
hormone (TSH) greater than 5 mIU/L has been used as an indicator of iodine
deficiency at the population level. However, TSH levels in newborns may be
influenced by many factors other than iodine status. The objective of this study
was to identify neonatal, maternal, and pregnancy-related determinants of
neonatal TSH levels in a retrospective cohort study. The study sample included
313 Belgian mothers and their 4- to 5-year-old children. The children had a
neonatal TSH concentration between 0 and 15 mIU/L at neonatal screening, and
blood samples were collected 3 to 5 days after birth. Children with suspected
congenital hypothyroidism (neonatal TSH level >15 mIU/L), prematurely born (i.e.,
<37 weeks), or with a low birth weight (i.e., <2500 g) were excluded. Information
about maternal and birth-related determinants was collected from the neonatal
screening center via a self-administered questionnaire filled in by the mother
together with the child's health booklet. Higher TSH levels were found in spring
and winter compared to summer and autumn (P = .011). Higher TSH levels were
associated with lifetime smoking behavior (up to child birth) in the mother (P =
.005), lower weight gain during pregnancy (P = .014), and longer pregnancies (P =
.003). This study showed that several neonatal, maternal, and pregnancy-related
determinants are influencing neonatal TSH level.
PMID- 26428624
TI - Variability of sedimentary organic carbon in patchy seagrass landscapes.
AB - Seagrass ecosystems, considered among the most efficient carbon sinks worldwide,
encompass a wide variety of spatial configurations in the coastal landscape. Here
we evaluated the influence of the spatial configuration of seagrass meadows at
small scales (metres) on carbon storage in seagrass sediments. We intensively
sampled carbon stocks and other geochemical properties (delta(13)C, particle
size, depositional fluxes) across seagrass-sand edges in a Zostera muelleri
patchy seagrass landscape. Carbon stocks were significantly higher (ca. 20%)
inside seagrass patches than at seagrass-sand edges and bare sediments.
Deposition was similar among all positions and most of the carbon was from
allochthonous sources. Patch level attributes (e.g. edge distance) represent
important determinants of the spatial heterogeneity of carbon stocks within
seagrass ecosystems. Our findings indicate that carbon stocks of seagrass areas
have likely been overestimated by not considering the influence of meadow
landscapes, and have important relevance for the design of seagrass carbon stock
assessments.
PMID- 26428623
TI - Probiotic and anti-inflammatory attributes of an isolate Lactobacillus helveticus
NS8 from Mongolian fermented koumiss.
AB - BACKGROUND: Koumiss is a traditionally fermented mare's milk described with
health-promoting potentials for decades. However, only a few studies focused on
the probiotic strains isolated from koumiss. In this study, we collected koumiss
samples from Inner Mongolian pasturing area of China and selected a promising
strain of Lactobacillus helveticus, isolate NS8, based on the survival abilities
in gastrointestinal tract (GIT) and adhesion to intestinal endothelial cells in
vitro. As the ability to positively modulate host immune response is a feature of
increasing importance in measuring the probiotic potential of a bacterial strain,
our study mainly focus on the immunomodulatory properties of L. helveticus NS8 by
using in vivo and ex vivo analyses. RESULTS: L. helveticus NS8 was identified by
molecular-typing methods, both at genus and species levels. As a typical food
niche-specific bacteria, NS8 showed a moderate survival ability in GIT
environment in vitro. However, an excellent binding capacity to the human
intestinal epithelial cells, along with significant autoaggregation and cell
surface hydrophobicity was observed. Additionally, the presence of S-layer
protein was responsible for the cell surface properties of this strain. NS8 was
found to be rather protective against TNBS (2,4,6-trinitrobenzene sulfonic acid)
induced murine colitis. In the meantime, co-culture with NS8 induced an increased
level of secretion of anti-inflammatory cytokine IL-10 in peripheral blood mono
nuclear cells (PBMCs). Furthermore, NS8 was also able to diminish the
proinflammatory effects of lipopolysaccharide (LPS) in mouse macrophage cell line
RAW264.7 by inducing higher levels of IL-10. Specially, adding of the purified S
layer protein didn't influence the production of IL-10. The specific ligand-host
receptor interactions on the NS8 specific immune responses need to be learned
further. CONCLUSION: In summary, L. helveticus NS8 exhibited good probiotic and
particularly immunomodulatory properties, with a potential for development of
functional food commercially or therapeutic adjuvant for inflammatory diseases.
PMID- 26428625
TI - Persistent organic pesticide residues in sediments of Vasai Creek near Mumbai:
Assessment of sources and potential ecological risk.
AB - Thirteen persistent organic pesticides were investigated in the sediments of
Vasai Creek near Mumbai to evaluate their pollution levels and potential risks.
It was observed that SigmaOCPs level was in the range of 597-1538ng/g dw, with an
average value of 1115.25ng/g dw. The level of SigmaOPPs was in the range of 492
1034ng/g dw, with an average value of 798.15ng/g dw. The values o,p'-DDT/p,p'-DDT
ratio gives an indication of use of technical DDT as the prime source of DDT,
while the alpha/gamma-BHC ratio indicate that BHCs in study area might have been
received from fresh lindane. The results of an ecological risk assessment showed
that sediment bound organic pesticides are of more ecotoxicological concern as
they might create adverse ecological risk to the marine breeding habitats. These
pesticides residues may get remobilize and released to overlying waters creating
adverse effects on terrestrial and aquatic organisms.
PMID- 26428626
TI - Prevalence, trends, patterns and associations of analgesic use in Germany.
AB - BACKGROUND: Despite the public health relevance of analgesic use, large-scale
studies on this topic in Germany are lacking. This study describes the
prevalence, trends, associations and patterns of use of prescription and over-the
counter (OTC) analgesics, focusing on five of the most common agents: aspirin,
diclofenac, ibuprofen, naproxen and paracetamol. METHODS: Data from two
representative population-based surveys: The German National Health Interview and
Examination Survey 1998 (GNHIES98 n = 7099) and the German Health Interview and
Examination Survey for Adults 2008-2011 (DEGS1 n = 7091) was investigated.
Information on all medicines consumed in the previous 7 days was collected via
computer-assisted personal interviews with adults aged 18-79 years. Associations
between analgesic use and socio-demographic and health-behaviour factors were
analysed using logistic regression models. RESULTS: Analgesic use has increased
over the last decade from 19 to 21%. This was exclusively due to the rise in OTC
analgesic use from 10.0 to 12.2%. Prescribed analgesic use remained constant
(7.9%). Findings from DEGS1 indicate that ibuprofen is the most commonly used
analgesic followed by aspirin and paracetamol. OTC analgesic use is higher among
women and smokers, but lower among older adults (65-79 years). Prescribed
analgesics use is higher among women, older adults, smokers and obese adults with
medium or high socio- economic status. Adults performing more than 2 h/week of
physical exercise use fewer analgesics. DISCUSSION: Among the adult population of
Germany, the prevalence of OTC analgesic use has significantly increased over the
last decade. We found differences between adults consuming OTC and prescribed
analgesics (or both) concerning their health behaviour and health conditions.
International direct comparison between prevalence rates of analgesic use was
limited due to varying availability of analgesics between countries and to
methodological differences. CONCLUSIONS: About one in five community dwelling
adults aged 18-79 years in Germany use analgesics in a given week. Considering
the potential harms of analgesic use, monitoring of prevalence, patterns and
determinants of use at the population level are important steps to inform disease
prevention and health promotion policies.
PMID- 26428627
TI - Validation of high temporal resolution spiral phase velocity mapping of temporal
patterns of left and right coronary artery blood flow against Doppler guidewire.
AB - BACKGROUND: Temporal patterns of coronary blood flow velocity can provide
important information on disease state and are currently assessed invasively
using a Doppler guidewire. A non-invasive alternative would be beneficial as it
would allow study of a wider patient population and serial scanning. METHODS: A
retrospectively-gated breath-hold spiral phase velocity mapping sequence (TR 19
ms) was developed at 3 Tesla. Velocity maps were acquired in 8 proximal right and
15 proximal left coronary arteries of 18 subjects who had previously had a
Doppler guidewire study at the time of coronary angiography. Cardiovascular
magnetic resonance (CMR) velocity-time curves were processed semi-automatically
and compared with corresponding invasive Doppler data. RESULTS: When corrected
for differences in heart rate between the two studies, CMR mean velocity through
the cardiac cycle, peak systolic velocity (PSV) and peak diastolic velocity (PDV)
were approximately 40 % of the peak Doppler values with a moderate - good linear
relationship between the two techniques (R(2): 0.57, 0.64 and 0.79 respectively).
CMR values of PDV/PSV showed a strong linear relationship with Doppler values
with a slope close to unity (0.89 and 0.90 for right and left arteries
respectively). In individual vessels, plots of CMR velocities at all cardiac
phases against corresponding Doppler velocities showed a consistent linear
relationship between the two with high R(2) values (mean +/-SD: 0.79 +/-.13).
CONCLUSIONS: High temporal resolution breath-hold spiral phase velocity mapping
underestimates absolute values of coronary flow velocity but allows accurate
assessment of the temporal patterns of blood flow.
PMID- 26428628
TI - PSR: polymorphic SSR retrieval.
AB - BACKGROUND: With the advent of high-throughput sequencing technologies large
scale identification of microsatellites became affordable and was especially
directed to non-model species. By contrast, few efforts have been published
toward the automatic identification of polymorphic microsatellites by exploiting
sequence redundancy. Few tools for genotyping microsatellite repeats have been
implemented so far that are able to manage huge amount of sequence data and
handle the SAM/BAM file format. Most of them have been developed for and tested
on human or model organisms with high quality reference genomes. RESULTS: In this
note we describe polymorphic SSR retrieval (PSR), a read counter and simple
sequence repeat (SSR) length polymorphism detection tool. It is written in Perl
and was developed to identify length polymorphisms in perfect microsatellites
exploiting next generation sequencing (NGS) data. PSR has been developed bearing
in mind plant non-model species for which de novo transcriptome assembly is
generally the first sequence resource available to be used for SSR-mining. PSR is
divided into two modules: the read-counting module (PSR_read_retrieval)
identifies all the reads that cover the full-length of perfect microsatellites;
the comparative module (PSR_poly_finder) detects both heterozygous and homozygous
alleles at each microsatellite locus across all genotypes under investigation.
Two threshold values to call a length polymorphism and reduce the number of false
positives can be defined by the user: the minimum number of reads overlapping the
repetitive stretch and the minimum read depth. The first parameter determines if
the microsatellite-containing sequence must be processed or not, while the second
one is decisive for the identification of minor alleles. PSR was tested on two
different case studies. The first study aims at the identification of polymorphic
SSRs in a set of de novo assembled transcripts defined by RNA-sequencing of two
different plant genotypes. The second research activity aims to investigate
sequence variations within a collection of newly sequenced chloroplast genomes.
In both the cases PSR results are in agreement with those obtained by capillary
gel separation. CONCLUSION: PSR has been specifically developed from the need to
automate the gene-based and genome-wide identification of polymorphic
microsatellites from NGS data. It overcomes the limits related to the existing
and time-consuming efforts based on tools developed in the pre-NGS era.
PMID- 26428630
TI - A measurement system analysis with design of experiments: Investigation of the
adhesion performance of a pressure sensitive adhesive with the probe tack test.
AB - The tack of a pressure sensitive adhesive (PSA) is not an inherent material
property and strongly depends on the measurement conditions. Following the
concept of a measurement system analysis (MSA), influencing factors of the probe
tack test were investigated by a design of experiments (DoE) approach. A response
surface design with 38 runs was built to evaluate the influence of detachment
speed, dwell time, contact force, adhesive film thickness and API content on
tack, determined as the maximum of the stress strain curve (sigmamax). It could
be shown that all investigated factors have a significant effect on the response
and that the DoE approach allowed to detect two-factorial interactions between
the dwell time, the contact force, the adhesive film thickness and the API
content. Surprisingly, it was found that tack increases with decreasing and not
with increasing adhesive film thickness.
PMID- 26428629
TI - Development of chitosan nanoparticles as drug delivery system for a prototype
capsid inhibitor.
AB - Oral delivery of biopharmaceutics drug disposition classification system (BDDCS)
Class II or IV drugs with poor aqueous solubility and poor enzymatic and/or
metabolic stability is very challenging. Bay41-4109, a member of the
heteroaryldihydropyrimidine (HAP) family, inhibits HBV replication by
destabilizing capsid assembly. It pertains to class II of the BDDCS which has a
practically insoluble solubility which is 38 MUg/mL (LYSA) and the oral delivery
resulted in low bioavailability. The purpose of the current research work was to
develop and evaluate Bay41-4109 loaded chitosan nanoparticles to increase the
solubility and bioavailability for treatment of HBV. The Bay41-4109 nanoparticles
were prepared by gelation of chitosan with tripolyphosphate (TPP) through ionic
cross-linking. A three-factor three-level central composite design (CCD) was
introduced to perform the experiments. A quadratic polynomial model was generated
to predict and evaluate the independent variables with respect to the dependent
variables. Bay41-4109 was encapsulated in the chitosan nanoparticles were
demonstrated by PLM, FTIR, DSC, XRD and TEM etc. The in vivo results suggest that
Bay41-4109 nanoparticles have better bioavailability and would be a promising
approach for oral delivery of Bay41-4109 for the treatment of HBV.
PMID- 26428631
TI - Evaluation of a biodegradable microparticulate polymer as a carrier for
Burkholderia pseudomallei subunit vaccines in a mouse model of melioidosis.
AB - Melioidosis, a potentially lethal disease of humans and animals, is caused by the
soil-dwelling bacterium Burkholderia pseudomallei. Due to B. pseudomallei's
classification as a Tier 1 Select Agent, there is substantial interest in the
development of an effective vaccine. Yet, despite decades of research, no
effective target, adjuvant or delivery vehicle capable of inducing protective
immunity against B. pseudomallei infection has been identified. We propose a
microparticulate delivery vehicle comprised of the novel polymer acetalated
dextran (Ac-DEX). Ac-DEX is an acid-sensitive biodegradable carrier that can be
fabricated into microparticles (MPs) that are relatively stable at pH 7.4, but
rapidly degrade after phagocytosis by antigen presenting cells where the pH can
drop to 5.0. As compared to other biomaterials, this acid sensitivity has been
shown to enhance cross presentation of subunit antigens. To evaluate this
platform as a delivery system for a melioidosis vaccine, BALB/c mice were
vaccinated with Ac-DEX MPs separately encapsulating B. pseudomallei whole cell
lysate and the toll-like receptor (TLR) 7/8 agonist resiquimod. This vaccine
elicited a robust antibody response that included both Th1 and Th2 immunity.
Following lethal intraperitoneal challenge with B. pseudomallei 1026b, vaccinated
mice demonstrated a significant delay to time of death compared to untreated
mice. The formulation, however, demonstrated incomplete protection indicating
that lysate protein offers limited value as an antigen. Nevertheless, our Ac-DEX
MPs may offer an effective delivery vehicle for a subunit B. psuedomallei
vaccine.
PMID- 26428632
TI - Development of multifunctional lipid nanocapsules for the co-delivery of
paclitaxel and CpG-ODN in the treatment of glioblastoma.
AB - In this work, multifunctional lipid nanocapsules (M-LNC) were designed to combine
the activity of the cytotoxic drug paclitaxel (PTX) with the immunostimulant CpG.
This nanosystem, consisting of modified lipid nanocapsules coated with a cationic
polymeric shell composed of chitosan (CS), was able to allocate the hydrophobic
drug PTX in the inner oily core, and to associate onto the surface the genetic
material CpG. The CS-coated LNC (CS-LNC), showed a narrow size distribution with
an average size of 70 nm and a positive zeta potential (+25 mV). They
encapsulated PTX in a high amount (98%), and, due to the cationic surface charge,
were able to adsorb CpG without losing stability. As a preliminary in vitro
study, the apoptotic effect on GL261 glioma cells was investigated. The drug
loaded CS-LNC exhibited the ability to interact with glioma cells and induce an
important apoptotic effect in comparison with blank systems. Finally, the M-LNC
made of CS-LNC loaded with both CpG and PTX were tested in vivo, injected via
convention enhanced delivery (CED) in GL261-glioma-bearing mice. The results
showed that the overall survival of mice treated with the M-LNC was significantly
increased in comparison with the control, Taxol((r)), or the separated injection
of PTX-loaded LNC and CpG. This effect was also confirmed by magnetic resonance
imaging (MRI) which revealed the reduction of tumor growth in the animals treated
with CpG and PTX-loaded M-LNC. All these findings suggested that the developed M
LNC could potentiate both CpG immunopotency and PTX antitumor activity by
enhancing its delivery into the tumor microenvironment.
PMID- 26428633
TI - An investigation into the influence of drug-polymer interactions on the
miscibility, processability and structure of polyvinylpyrrolidone-based hot melt
extrusion formulations.
AB - While hot melt extrusion is now established within the pharmaceutical industry,
the prediction of miscibility, processability and structural stability remains a
pertinent issue, including the issue of whether molecular interaction is
necessary for suitable performance. Here we integrate the use of theoretical and
experimental drug-polymer interaction assessment with determination of
processability and structure of dispersions in two polyvinylpyrrolidone-based
polymers (PVP and PVP vinyl acetate, PVPVA). Caffeine and paracetamol were chosen
as model drugs on the basis of their differing hydrogen bonding potential with
PVP. Solubility parameter and interaction parameter calculations predicted a
greater miscibility for paracetamol, while ATR-FTIR confirmed the hydrogen
bonding propensity of the paracetamol with both polymers, with little interaction
detected for caffeine. PVP was found to exhibit greater interaction and
miscibility with paracetamol than did PVPVA. It was noted that lower processing
temperatures (circa 40 degrees C below the Tg of the polymer alone and Tm of the
crystalline drug) and higher drug loadings with associated molecular dispersion
up to 50% w/w were possible for the paracetamol dispersions, although molecular
dispersion with the non-interactive caffeine was noted at loadings up to 20%
w./w. A lower processing temperature was also noted for caffeine-loaded systems
despite the absence of detectable interactions. The study has therefore indicated
that theoretical and experimental detection of miscibility and drug-polymer
interactions may lead to insights into product processing and extrudate
structure, with direct molecular interaction representing a helpful but not
essential aspect of drug-polymer combination prediction.
PMID- 26428634
TI - Using simple technology to prompt multistep tasks in the home for people with
dementia: An exploratory study comparing prompting formats.
AB - Objectives To investigate the relative effectiveness of different prompts for
people with dementia during multistep tasks in the home, to inform prompting
technology design. Methods Nine pairs of participants (one with dementia and a
partner or relative) participated at home. The participants with mild to moderate
dementia (5M/4F, aged 73-86 years) functioned at the Planned or Exploratory
levels of the Pool Activity Level instrument. A touchscreen computer displayed
different prompts during two set tasks: "card-and-envelope" and "CD player." The
trials were scored to establish the relative effectiveness of the prompts.
Individual tasks were also explored. Results Text and audio prompts were each
more effective than video or picture prompts for a card-and-envelope task, but
this was not seen in a CD player task. The differences may be related to the type
of actions within the tasks; the card-and-envelope actions were easier to convey
verbally; the CD player actions lent themselves to visual prompts. Conclusions
Designers of technology-based prompts for people with dementia should consider
that the effectiveness of different prompts is likely to be task dependent.
Familiar, unambiguous language can increase the success of tailored prompts.
There are significant practical challenges associated with choosing and
deconstructing everyday tasks at home.
PMID- 26428635
TI - Understanding the determinants of under-five child mortality in Uganda including
the estimation of unobserved household and community effects using both
frequentist and Bayesian survival analysis approaches.
AB - BACKGROUND: Infant and child mortality rates are among the health indicators of
importance in a given community or country. It is the fourth millennium
development goal that by 2015, all the United Nations member countries are
expected to have reduced their infant and child mortality rates by two-thirds.
Uganda is one of those countries in Sub-Saharan Africa with high infant and child
mortality rates, therefore it is important to use sound statistical methods to
determine which factors are strongly associated with child mortality which in
turn will help inform the design of intervention strategies METHODS: The Uganda
Demographic Health Survey (UDHS) funded by USAID, UNFPA, UNICEF, Irish Aid and
the United Kingdom government provides a data set which is rich in information on
child mortality or survival. Survival analysis techniques are among the well
developed methods in Statistics for analysing time to event data. These methods
were adopted in this paper to examine factors affecting under-five child
mortality rates (UMR) in Uganda using the UDHS data for 2011 in R and STATA
software. RESULTS: Results obtained by fitting the Cox-proportional hazard model
with frailty effects and drawing inference using both the frequentists and
Bayesian approaches at 5 % significance level, show evidence of the existence of
unobserved heterogeneity at the household level but there was not enough evidence
to conclude the existence of unobserved heterogeneity at the community level. Sex
of the household head, sex of the child and number of births in the past one year
were found to be significant. The results further suggest that over the period of
1990-2015, Uganda reduced its UMR by 52 % . CONCLUSION: Uganda has not achieved
the MDG4 target but the 52 % reduction in the UMR is a move in the positive
direction. Demographic factors (sex of the household head) and Biological
determinants (sex of the child and number of births in the past one year) are
strongly associated with high UMR. Heterogeneity or unobserved covariates were
found to be significant at the household but insignificant at the community
level.
PMID- 26428637
TI - Benign Prostatic Hyperplasia - An economic assessment of fixed combination
therapy based on a literature review.
AB - FederAnziani Senior Italia and SIU - Italian Society of Urology - have decided to
work together to draft a document focussing on Benign Prostatic Hyperplasia
(BPH), and to stress the importance of adherence with pharmacological treatment
in this setting, from both a scientific and a patient standpoint. Starting from a
literature search, the two associations analysed to what extent an increase in
treatment adherence amongst these patients influences hospital savings and to
what extent therapy persistence levels are affected by monotherapy rather than
free drug combinations. These estimates were performed only on patients taking
medicinal products belonging to the 5 alpha-reductase inhibitors (5ARI) class
that, although not indispensable, are the compounds that bring the greatest
benefits, especially in the elderly and for which we know that every additional
30 days of therapy reduced the likelihood of acute urinary retention (AUR) and
surgery by 14% and 11% respectively *. The results show that the use of fixed
combination therapy would involve an increase in persistence due to the lower
rate of patients abandoning treatment over time. Each 30 day-increment of 5ARI
therapy, i.e. for an expenditure of 10.6 million euros extra per year for 5ARI
medication, savings of approximately 24.3 million euros in hospital costs could
be achieved.
PMID- 26428636
TI - Increased IGF-IEc expression and mechano-growth factor production in intestinal
muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy.
AB - The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans.
In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-beta1 induces IGF
IEa expression and IGF-I production in intestinal smooth muscle and results in
muscle hyperplasia and collagen I production that contribute to stricture
formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and
cardiac muscle hypertrophy following stress. We hypothesized that increased IGF
IEc expression and MGF production mediated smooth muscle hypertrophy also
characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF
protein were increased in muscle cells isolated from fibrostenotic intestine
under regulation by endogenous TGF-beta1. Erk5 and MEF2C were phosphorylated in
vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus
in response to synthetic MGF in vitro. Smooth muscle-specific protein expression
of alpha-smooth muscle actin, gamma-smooth muscle actin, and smoothelin was
increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth
muscle-specific gene expression and hypertrophy induced by synthetic MGF.
Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy
that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The
results indicate that TGF-beta1-dependent IGF-IEc expression and MGF production
in patients with fibrostenotic Crohn's disease regulates smooth muscle cell
hypertrophy a critical factor that contributes to intestinal stricture formation.
PMID- 26428638
TI - Improvement of seminal quality and sexual function of men with
oligoasthenoteratozoospermia syndrome following supplementation with L-arginine
and Pycnogenol(r).
AB - We evaluated the effectiveness of antioxidant co-supplementation therapy using
Larginine and Pycnogenol((r)) in Japanese men with oligoasthenozoospermia and
mild erectile dysfunction (ED). A total of forty-seven adult males with
oligoasthenoteratozoospermia syndrome (OAT) were eligible for enrollment. The
effectiveness of supplementation with a combination of L-arginine 690 mg and
French maritime pine bark extract (Pycnogenol((r))) 60mg for OAT and ED was
investigated. The sperm concentration was enhanced significantly after treatment
2 and 4 months (11.79 +/- 9.86 to 21.22 +/- 28.17 and 20.15 +/- 23.99 * 106/ml).
Significant improvements in the International Index of Erectile Function (IIEF)
were observed in the total score of IIEF (57.69 +/- 11.04 to 59.43 +/- 12.57) and
domain of Orgasmic Function (9.01 +/- 1.92 to 9.34 +/- 1.66) after 4 months of
treatment. L-arginine acts to increase the production of nitric oxide and
Pycnogenol((r)) activates the endothelial nitric oxide synthase and it is a
potent antioxidant and inhibitor of inducible nitric oxide synthase. This study
suggests that the combination of Pycnogenol((r)) and L-arginine (Edicare((r))) is
helpful for infertile men to ameliorate simultaneously quality of sperms as well
as erectile functions.
PMID- 26428639
TI - The relationship between serum hormone levels (follicle-stimulating hormone,
luteinizing hormone, total testosterone) and semen parameters.
AB - OBJECTIVE: The aim of this study was to investigate the effect of serum
gonadotropin and total testosterone levels on semen parameters. MATERIALS AND
METHODS: Three hundred and eighty-two patients that applied to a male infertility
polyclinic were included in our study. Serum gonadotropin and total testosterone
levels and semen parameters of the patients were analyzed during the first visit
to the clinic. The reference FSH value was 1.5-12.4 mIU/mL, that of LH was 1.7
8.6 mIU/mL and the reference value for total testosterone was 249-836 ng/dL.
RESULTS: While there was no statistically significant difference between the
patients with low gonadotropin levels and the controls regarding any of the semen
parameters (p > 0.05), there was a strong statistically significant difference
between the patients with high gonadotropin levels and the controls regarding
sperm concentration (p = 0.000), total motility (p = 0.000), progressive motility
(p = 0.000), and morphology (p = 0.000). There was a strong statistically
significant difference between the patients with low testosterone levels and the
controls regarding total motility (p = 0.012) and progressive motility (p =
0.010), and a weak statistically significant difference in morphology (p =
0.042). There was no statistically significant difference in semen volume or
sperm concentration (p > 0.05). There was no statistically significant difference
in any of the semen parameters between the patients with high testosterone levels
and the controls (p > 0.05). CONCLUSIONS: Our findings especially regarding LH
and T levels are not in agreement with previous reports. In this regard, there is
a need for larger-scale and randomized trials to resolve this discrepancy.
PMID- 26428641
TI - PDE-5 inhibitors in monotherapy versus combination therapy in a sample of 1200
patients with erectile dysfunction.
AB - OBJECTIVES: To compare the effectiveness in the treatment of erectile dysfunction
when using PDE-5 inhibitors (PDE5i), alprostadil (PG-E1) and testosterone (TES)
in monotherapy or combination therapy. MATERIAL AND METHODS: Observational
multicentre retrospective study of men diagnosed and treated for ED between
January 2008 and January 2014. Age, social and employment situation, pathological
medical history, risk factors, usual treatments, IIEF-5 at the first consultation
and at first and each 6 months follow-ups, physical examination, calculated total
and free testosterone and received treatment were analysed. Descriptive
statistics, one-way ANOVA analysis, Chi2 for qualitative data, t-test, Fisher's
exact test and Pearson's correlation coefficient were used; p < 0.05 is
considered significant. RESULTS: Average age was 58.61 years, SD5.02, average
follow- up time 48.21 months, SD 6.21, range 6-174 months. Out of the patients
76.12% were married, 9.81% divorced/separated, 10.04% single, 4.03% widowed;
85.14% of the total in stable partnership but 66.16% were not accompanied by
their partners. In total 844 patients received monotherapy (597 PDE5i; 62 PG-E1;
36 TES; 27 penile prosthesis; 121 psychotherapy/alternative therapies) and 357
combination therapy (167 PDE5i+TES; 124 PDE5i+PGE1; 66 PG-E1+TES). There was a
homogeneous distribution between risk factors and medical history groups.
Satisfactory response according to IIEF-5 was achieved for 72.33% of patients on
PDE5i monotherapy, 46.65% of patients on PDE5i+PG-E1 combination therapy and
83.41% of patients on PDE5i+TES. CONCLUSIONS: The best therapeutic success for ED
in this series was achieved through a combination of testosterone+PDE-5
inhibitors without increasing morbidity and maintaining the response over time.
Larger studies with longer follow-up will corroborate these findings.
PMID- 26428640
TI - The histology and the proapoptotic control in the ipsilateral and the
contralateral testes following unilateral vasectomy.
AB - OBJECTIVE: The aim of this study was to enlighten both the testicular histology
and the genetic aspects of the apoptotic process. Thus an experimental study was
designed with a model of unilateral vasectomy. METHODS: Twenty-two adult male
rats were used and 4 main groups were formed. The first (A), the second (B), the
third (C), and the fourth group (D) consisted of 4, 4, 4 and 10 rats
respectively. Rats in group A had sham operation while rats in other groups (B,
C, D) underwent left vasectomy operation including binding of ductus deferens
with a 3/0 silk and cutting a minimum of 1 cm part while preserving the vascular
structure under 9x magnification. Rats undergoing unilateral vasectomy were
sacrificed at the 1(st), 2(nd) and 8(th) weeks and their testicular structure and
proapoptotic gene proteins were compared with that of the control group
undergoing sham operation. RESULTS: We found that vasectomy gradually caused
destruction and both ipsilateral and contralateral testicles were affected
showing initial apoptosis. CONCLUSION: The procedure causes destruction in the
testicular structure by causing bilateral intratubular germ cell necrosis,
unilateral obstruction, increase in the tubular pressure and processes that are
aggravated by some probable autoimmune reactions.
PMID- 26428642
TI - Once-a-day Tadalafil administration improves the spermogram parameters in fertile
patients.
AB - OBJECTIVES: We explored the safety of Tadalafil once-daily treatment for 12 week
and its effects on semen quality in a clinical subpopulation of men with
psychogenic erectile dysfunction (ED). PATIENTS AND METHODS: Twenty-seven men,
between 19 and 35 years, unaware of their fertility status, suffering from
psychogenic ED were enrolled. The examination of the seminal fluid was performed
twice before administration of Tadalafil and twice after three months of
continuous daily administration of Tadalafil 5 mg. The volume of the seminal
fluid, the concentration of sperm, the concentration of sperm with type "a+b"
motility, the concentration of sperm with type "a" motility, the concentration of
normal sperm were taken into consideration. The results before treatment with
Tadalafil (T0) and after 3 months of treatment (T3m) were compared. RESULTS: The
administration of once-daily Tadalafil 5mg, brings to an average increase of the
total number of sperm cells, both total and fast motility (type a) and the
percentage of nemasperms, and to an average increase of semen volume of only 0.41
ml. These quantitative and qualitative improvements of the seminal fluid resulted
statistically significant as regard motility, nemasperm percentage and seminal
fluid volume. No unespected safety findings were observed. CONCLUSIONS: Tadalafil
administration improves the quality of sperm cells and seminal fluid: in
particular motility, percentage of nemasperms and volume of seminal fluid. We
emphasize the safety of the once-daily treatment with tadalafil 5mg and the
positive effects on spermatogenesis.
PMID- 26428643
TI - Sexual activity and the risk of prostate cancer: Review article.
AB - INTRODUCTION: Sexual activity can affect prostate cancer pathogenesis in a
variety of ways; including the proposed high androgen status, risk of sexually
transmitted infections and the potential effect of retained carcinogens within
the prostatic cells. METHODS: PubMed review of all publications concerning sexual
activity and the risk of prostate cancer was done by two researchers. RESULTS:
Few publications could be detected and data were classified as a prostate cancer
risk in association with either heterosexual or homosexual activities.
CONCLUSION: Frequent ejaculation seems to be protective from the development of
prostate cancer. Multiple sexual partners may be protective from prostate cancer,
excluding the risk of sexually transmitted infections. Homosexual men are at a
greater risk for the diagnosis of prostate cancer.
PMID- 26428644
TI - 500 penile prostheses implanted by a surgeon in Italy in the last 30 years.
AB - OBJECTIVES: The aim of our study was to report our experience with patients
affected by Erectile Dysfunction (ED) and undergoing penile prosthetic
implantation (PPI) in a single center by a single surgeon. MATERIAL AND METHODS:
We retrospectively evaluated the clinical outcome of 500 patients (mean age: 51.5
years, range: 20-86 years) affected by ED and referred to our private
andrological center from January 1984 to December 2013 who underwent penile
prosthesis implantation, including the reported level of patient satisfaction.
RESULTS: 182 silicone, 180 malleable, 18 monocomponent hydraulic and 120
multicomponents hydraulic prostheses were implanted by the same experienced
surgeon. All patients were hospitalized for the procedure. All patients were
evaluated immediately, 1 month (496 patients) and, for the great majority, every
year after implantation. One hundred twenty five patients were lost to follow-up.
Twenty two patients underwent revision surgery for complications in the
postoperative period. The most serious postoperative complications were
mechanical problems (45 patients, 9.0%) and infection (15 patients, 3%). Forty
two (8.4%) prostheses were explanted. Overall, 80% (400/500) of patients were
able to have sexual intercourse and were fully satisfied with the results.
CONCLUSIONS: In our experience prosthetic surgery should be considered a good
solution for men affected by ED and not responsive to other therapeutic
solutions. Prosthetic surgery can be performed not only in large public hospitals
but also in smaller private facilities.
PMID- 26428645
TI - Androgen deprivation therapy (castration therapy) and pedophilia: What's new.
AB - Andrology is a constantly evolving discipline, embracing social problems like
pedophilia and its pharmacological treatment. With regard to chemical castration,
the andrologist may perform an important role as part of a team of specialists.
At present, no knowledge is available regarding hormonal, chromosomal or genetic
alterations involved in pedophilia. International legislation primarily aims to
defend childhood, but does not provide for compulsory treatment. We reviewed
international literature that, at present, only comprises a few reports on
research concerning androgen deprivation. Most of these refer to the use of
leuprolide acetate, rather than medroxyprogesterone and cyproterone acetate,
which present a larger number of side effects. Current opinions on chemical
castration for pedophilia are discordant. Some surveys confirm that therapy
reduces sexual thoughts and fantasies, especially in recidivism. On the other
hand, some authors report that chemical castration does not modify the
pedophile's personality. In our opinion, once existing legislation has changed,
andrologists could play a significant role in the selection of patients to
receive androgen deprivation therapy, due in part to their knowledge about its
action and side effects.
PMID- 26428646
TI - Stone size and quality of life: A critical evaluation after extracorporeal shock
wave lithotripsy.
AB - OBJECTIVES: To evaluate the quality of life (QoL) of the patients after
extracorporeal shockwave lithotripsy (ESWL) on a treated stone size related
basis. METHODS: 90 patients undergoing ESWL for kidney stones were divided into
three groups; Group 1 (n: 30, <= 10 mm), Group 2 (n: 28, 11 mm- <= 20 mm) and
Group 3 (n: 32, 20- 25 mm). During 3- months follow-up, outcome of the procedure,
number of cases with emergency department visits, analgesic required, re
tretatment rates, additional procedures and the changes in the QoL were
evaluated. RESULTS: the number of emergency department visits and mean analgesic
need; re-treatment rates and additional procedures were significantly higher in
Group 3. Evaluation of the QoL scores in three groups showed that cases with
larger stone still had lower scores during 3-month evaluation. CONCLUSIONS: Stone
size could help us to predict the possible impact of ESWL on the QoL and
depending on the size of the stone treated, a well planned indication and
effective management possibly by an experienced urologist could limit the changes
in the QoL of the patients.
PMID- 26428648
TI - Clinical significance of prostatic-urethral angulation on the treatment outcome
of patients with symptomatic benign prostatic hyperplasia treated with tamsulosin
hydrochloride.
AB - OBJECTIVES: To evaluate the impact of the prostatic-urethral angulation (PUA) on
the treatment efficacy of selective alpha-1A receptor blocker in male patients
with lower urinary tract symptoms secondary to benign prostatic hyperplasia
(LUTS/BPH). MATERIALS AND METHODS: A total of 80 patients with LUTS/BPH and with
mean age 53.3 +/- 6.3 (range 47-70) were included in our prospective comparative
study. The patients were classified into 2 groups as a consecutive cases 40 in
each one depending on the PUA either <= 35 degrees (group A) or > 35 degrees
(group B). PUA and different prostatic parameters were measured using transrectal
ultrasound. Prostate-specific antigen (PSA), the International Prostate Symptom
Score and quality of life score (IPSS/QoL score), maximum flow rate (Qmax), and
postvoid residual (PVR) volume were compared between the groups. The clinical
significance of PUA was evaluated after 8 weeks of medical treatment with
tamsulosin hydrochloride 0.4 mg daily. RESULTS: Baseline evaluation (pre
treatment) for both groups were comparable to each other with no clinically
significant difference regarding age, PSA, IPSS/QoL score, Q(max) and PVR volume
(P-value > 0.05). Comparison of parameters after 8 weeks showed that tamsulosin
hydrochloride improved the total IPSS and all subscores (P < 0.001), QoL (P =
0.001), Q(max) (P = 0.002), and PVR (P = 0.04) in group A (Table 1). CONCLUSION:
Tamsulosin hydrochloride appears to be less effective in improving IPSS/Qol
score, Qmax and PVR in patients with lager PUA. The PUA might be a predictor for
the treatment efficacy of alpha-blockers and more studies are warranted in the
future before the final conclusion.
PMID- 26428647
TI - A two staged treatment procedure for the difficult to treat bladder neck
contractures with concomitant incontinence. In the search of a solution to a
complex problem.
AB - OBJECTIVE: To examine the efficacy of a two staged treating strategy with the use
of a non-permanent urethral ALLIUM((r)) stent for the management of recurrent
bladder neck stenosis and subsequently the use of an artificial sphincter
AUS800((r)) by AMS for the management of the incontinence. MATERIALS AND METHODS:
We progressively identified patients eligible for the study creating a population
of cases with recurrent bladder neck stenosis and concomitant incontinence
occurring after the last intervention for the stenosis. Efficacy for the
treatment of the stenosis was defined as no recurrence both prior and post to the
sphincter placement and efficacy for the treatment of the incontinence was
defined as continence (0-1pads) after the sphincter placement. RESULTS AND
LIMITATIONS: 14 white males with a mean age of 66.21, ranging from 59 to 73 years
consisted the population of the study. All patients had severe stress
incontinence following the last transurethral resection. The efficacy of the
treatment of the bladder neck stenosis was 93% (13/14) while the efficacy for the
treatment of the incontinence was 100%. A single patient had a recurrent bladder
neck stenosis after the artificial sphincter placement and was treated with
transurethral resection using a long pediatric 13 F resectoscope at 12 months.
Our limitations is the absence of a control group and the small number of
patients enrolled, with a relatively short time of follow up. CONCLUSIONS: In our
series we propose the use of a non-permanent urethral ALLIUM((r)) stent for 6
months in order to control the growth of fibrotic scar tissue, a further 6 months
follow up for recurrence, and then placement of an artificial sphincter. The
results are very promising both on stabilizing the vesicourethral stenosis, and
on patient safety and tolerability.
PMID- 26428649
TI - Urinary incontinence: Clinical observation on 30 patients undergoing treatment
with F.R.E.M.S (Frequency Rhythmic Electrical Modulation System).
AB - AIM OF THE STUDY: Urge incontinence is considered to be a dysfunctional pathology
of social interest due to the psychological and relational implications of such
disability, the elevated number of affected patients and the consequent treatment
costs. We propose an innovative non-pharmacological and non-invasive care
methodology: Frequency rhythmic electrical modulation system (F.R.E.M.S.) therapy
(FT), based on the administration of electric fields of monophasic pulsed,
negative, asymmetric current, generated by a neurostimulator with the
characteristics of low variable frequency, high voltage and very low impulse
duration. MATERIAL AND METHODS: 30 patients were studied with urodynamic
evaluation and radiological diagnostic techniques, and underwent 2 cycles of 15
days therapy, with a 12 months follow-up. RESULTS: In 93% of cases, we obtained a
positive result, with either disappearance or improvement of symptoms.
CONCLUSION: Although the Authors believe that clinical results deserve further
neurohistological and immunohistochemical studies, in order to define the
anathomophysiological and biochemical changes induced by FT, they propose it as a
possible alternative to traditional pharmacological therapy and electrical
stimulation.
PMID- 26428651
TI - Late-onset secondary nocturnal enuresis in adolescents associated with post
traumatic stress disorder developed after a traffic accident.
AB - Secondary nocturnal enuresis is generally seen between 5 and 7 years of age and
it is rarely encountered when compared with the primary incontinence. Patients
with suggested diagnosis of secondary nocturnal enuresis should be examined for
neurological and spinal anomalies and diabetes mellitus, diabetes insipidus,
renal failure and urinary tract infection should be ruled out in differential
diagnosis (1-3). Herein, we are presenting case reports of adolescent patients
with secondary nocturnal enuresis refractory to medical therapy and developed
after in-vehicle and extravehicular accidents.
PMID- 26428650
TI - A new ultrasound and clinical classification for management of prostatic abscess.
AB - OBJECTIVES: In literature, most of the published data regarding prostatic abscess
(PA) are case reports, whereas there is no standardization of the diagnostic and
therapeutic routines. The purpose of this study is a new classification of
ultrasound imaging of PA with clinical features correlation. MATERIAL AND
METHODS: We retrospectively analysed the ultrasound database archives and
performed a MEDLINE(r) research of the peer reviewed literature on diagnosis and
case reports of PA using the terms "prostate and abscess". RESULTS: PA can be
classified into five Types: Type I - PA is present focally in a prostate lobe (<=
10 mm). Type II - PA is present in a prostate lobe (> 10 mm) and/or partially
overcrosses the border of the midline prostatic glandular. Type III - PA is
present in both glandular lobes form of multifocal areas (<= 10 mm). Type IV - PA
is present in both glandular lobes form of multifocal areas (> 10 mm). Type V -
PA involving intra or extraprostatic structures (bladder, urethra, seminal
vesicles and prostatic capsule). The different ultrasound imaging and diagnostic
criteria are listed for each type and subtype. CONCLUSIONS: The sonographic
pattern of PA is usually characteristic and easily differentiated from other
glandular lesions. The purpose of the study was to associate the use of TRUS to a
clinical standardized classification in order to facilitate PA diagnosis and
localization directing the clinician treatment to the correct management and
adequate therapeutic treatment.
PMID- 26428652
TI - 10-year survival of a patient with metastatic prostate cancer: Case report and
literature review.
AB - Prostate cancer is the most common malignancy in men. The 5-year relative
survival for all stages combined is 98.8%. Patients diagnosed with metastatic
prostate cancer have median survival from 2 to 3 years. We describe a case of 64
year old man who clinically presented with inguinal lymphadenopathy. Because of
elevated PSA levels biopsy of prostate was done and adenocarcinoma was diagnosed.
Biopsy of inguinal lymph nodes confirmed the diagnosis of prostate cancer.
Hormonal treatment was started and at the most recent follow-up, 10 years later,
the patient is asymptomatic with no clinical signs of disseminated disease.
PMID- 26428653
TI - Treatment of urethral strictures with balloon dilation: A forgotten tale.
AB - Urethral stricture is a common condition that can lead to serious complications
such as urinary infections and renal insufficiency secondary to urinary
retention. Treatment options include catheterization and dilation, urethroplasty
and endoscopic internal urethrotomy as well. Although treatment option depends on
the type, length and aetiology of stricture, the choice can be influenced to
varying degrees by the simplicity of the method, the preferences of the patient
the available accoutrements and the patient health condition. Both urethroplasty
and endoscopic internal urethrotomy require anaesthesia and thus are not suitable
for many elder and unfit for surgical treatment patients. On the other hand,
dilations are easy to perform in every day clinical practice however they have
been associated with iatrogenic urethral trauma. In contrast, balloon dilation
under vision dilates by radial application of forces against the stricture,
avoiding the potentially shearing forces associated with sequential rigid
dilation. Since it reduces the possibility of an iatrogenic urethral trauma and
the subsequent spongiofibrosis may lead into improved therapeutic outcomes. In
this report we describe a technique for the treatment of urethral strictures with
balloon dilation in elder and unfit for surgical treatment patients.
PMID- 26428654
TI - Contralateral tumor seeding of renal cell carcinoma mimicking late metastasis of
liver after laparoscopic nephrectomy: A case report with review of the
literature.
AB - Laparoscopic surgery has been increasingly used every day in the management of
urologic malignancies. Even though it seems as a minimally invasive surgery,
during these interventions tumor seeding, as seen in open surgery, confronts us
as a rarely seen serious risk. Herein, we have reported a case who demonstrated
peritoneal tumor implantation at 12 month postoperative follow up after
laparoscopic radical nephrectomy (LRN) performed for Furhman grade 1 (T2N0M0)
renal cell cancer.
PMID- 26428656
TI - Sex-related penile fracture with complete urethral rupture: A case report and
review of the literature.
AB - OBJECTIVE: To present the management of a patient with partial disruption of both
cavernosal bodies and complete urethral rupture and to propose a non-systematic
review of literature about complete urethral rupture. MATERIAL AND METHOD - CASE
REPORT: A 46 years old man presented to our emergency department after a blunt
injury of the penis during sexual intercourse. On physical examination there was
subcutaneous hematoma extending over the proximal penile shaft with a dorsal-left
sided deviation of the penis and urethral bleeding. Ultrasound investigation
showed an hematoma in the ventral shaft of the penis with a discontinuity of the
tunica albuginea of the right cavernosal corporum. The patient underwent
immediate emergency surgery consisted on evacuation of the hematoma, reparation
the partial defect of both two cavernosal bodies and end to end suture of the
urethra that resulted completely disrupted. RESULTS: The urethral catheter was
removed at the 12-th postoperative day without voiding symptoms after a
retrograde urethrography. 6 months postoperatively the patients was evaluated
with uroflowmetry demonstrating a max flow rate of 22 ml/s and optimal functional
outcomes evaluated with validated questionnaires. 8 months after surgery the
patients was evaluated by dynamic magnetic resonance (MRI) of the penis showing
only a little curvature on the left side of the penile shaft. CONCLUSION: Penile
fracture is an extremely uncommon urologic injury with approximately 1331
reported cases in the literature till the years 2001. To best of our knowledge
from 2001 up today, 1839 more cases have been reported, only in 159 of them
anterior urethral rupture was associated and in only 22 cases a complete urethral
rupture was described. In our opinion, in order to prevent long term
complications, in case of clinical suspicion of penile fracture, especially if it
is associated to urethral disruption, emergency surgery should be the first
choice of treatment.
PMID- 26428655
TI - Distal corpus cavernosum fibrosis and erectile dysfunction secondary to non
ischaemic priapism.
AB - Non-ischaemic priapism is a rare type of priapism and is associated with penile
or perineal trauma. The absence of ischaemia should theoretically prevent smooth
muscle necrosis and corporal fibrosis which occurs in ischaemic priapism. The aim
of this study was to first report a patient series with non-ischaemic priapism
that developed distal corpus cavernosum fibrosis and erectile dysfunction. Over a
5 year period, a cohort of 6 patients diagnosed with non-ischaemic priapism
presented to a single centre. The diagnosis was based on a clinical history,
penile examination with confirmation using a combination of cavernosal blood gas
analysis, colour duplex ultrasonography of the penis and angiography. Patients
were followed up in clinic at regular intervals with clinical examination and
repeat imaging. Following a median follow up of 4 weeks (range 2-12) the patients
reported either the development of erectile dysfunction with distal penile
flaccidity. Five patients required the use of PDE-5 inhibitors to achieve full
tumescence. The remaining patient eventually underwent insertion of a penile
prosthesis due to the failure of pharmacotherapies. Based on these findings we
suggest that superselective embolisation of non-ischaemic priapism cases
occasionally should be performed after a shorter period of conservative
treatment.
PMID- 26428658
TI - The Radiology of Osteoporotic Vertebral Fractures Redux.
AB - When a low-energy fracture occurs, then osteoporosis has progressed to the point
of bony structural failure. Because vertebral fractures are the commonest type of
osteoporotic fracture, the correct identification of them becomes important for
diagnosis, risk estimation, and management. However, there are no uniformly
agreed criteria for their diagnosis. The purpose of this review was to examine
the diagnostic radiological strategies available and suggest a coherent approach
to diagnosis. Diagnosis had come to focus on comparative changes in vertebral
dimensions. However, it has become apparent that mild reductions in vertebral
height are of uncertain implication. The importance of structural damage in
diagnosis has become recognized in parallel. Relative reductions in vertebral
height may not be a necessary nor sufficient criterion by which to diagnose a
fracture.
PMID- 26428657
TI - Parathyroid hormone 1 receptor is essential to induce FGF23 production and
maintain systemic mineral ion homeostasis.
AB - Parathyroid-hormone-type 1 receptor (PTH1R) is extensively expressed in key
regulatory organs for systemic mineral ion homeostasis, including kidney and
bone. We investigated the bone-specific functions of PTH1R in modulating mineral
ion homeostasis by generating a novel mouse model in which PTH1R is ablated in
the limb mesenchyme using Prx1Cre transgenic mice. Such ablation decreased FGF23
protein and serum levels by 50%, despite normal Fgf23 mRNA levels in long bones.
Circulating calcium and PTH levels were unchanged, but inorganic phosphate and
1,25(OH)2D3 levels were significantly decreased and accompanied by elevated
urinary calcium and phosphate wasting. Key renal genes for balancing mineral ion
homeostasis, calbindinD28k, Klotho, and Napi2a were suppressed by 30-40%.
Intermittent hPTH(1-34) injections increased Fgf23 mRNA (7.3-fold), Nurr1 mRNA
(3.1-fold), and serum intact-FGF23 (1.6-fold) in controls, but failed to induce
Fgf23, Nurr1 mRNA, or intact FGF23 production in mutants. Moreover, a significant
elevation in serum C-terminal-FGF23 levels (4-fold) was detected in both
genotypes. PTH markedly downregulated Galnt3 expression (2.7-fold) in controls
but not in mutants. These results demonstrate the pivotal role of PTH1R in long
bones to regulate systemic mineral ion homeostasis and the direct induction of
FGF23 by PTH1R signaling.
PMID- 26428659
TI - A new algorithm to improve assessment of cortical bone geometry in pQCT.
AB - High-resolution peripheral quantitative computed tomography (HR-pQCT) is now
considered the leading imaging modality in bone research. However, access to HR
pQCT is limited and image acquisition is mainly constrained only for the distal
third of appendicular bones. Hence, the conventional pQCT is still commonly used
despite inaccurate threshold-based segmentation of cortical bone that can
compromise the assessment of whole bone strength. Therefore, this study addressed
whether the use of an advanced image processing algorithm, called OBS, can
enhance the cortical bone analysis in pQCT images and provide similar information
to HR-pQCT when the same volumes of interest are analyzed. Using pQCT images of
European Forearm Phantom (EFP), and pQCT and HR-pQCT images of the distal tibia
from 15 cadavers, we compared the results from the OBS algorithm with those
obtained from common pQCT analyses, HR-pQCT manual analysis (considered as a gold
standard) and common HR-pQCT analysis dual threshold technique.We found that the
use of OBS segmentation method for pQCT image analysis of EFP data did not result
in any improvement but reached similar performance in cortical bone delineation
as did HR-pQCT image analyses. The assessments of cortical cross-sectional bone
area and thickness by OBS algorithm were overestimated by less than 4% while area
moments of inertia were overestimated by ~5-10%, depending on reference HR-pQCT
analysis method. In conclusion, this study showed that the OBS algorithm
performed reasonably well and it offers a promising practical tool to enhance the
assessment of cortical bone geometry in pQCT.
PMID- 26428660
TI - Radiofrequency ablation plus chemoembolization versus radiofrequency ablation
alone for hepatocellular carcinoma: A systematic review and meta-analysis.
AB - BACKGROUND: To determine whether the use of radiofrequency ablation (RFA) plus
transcatheter arterial chemoembolization (TACE) is more effective than the use of
RFA alone for patients with hepatocellular carcinoma (HCC). METHODS: A computer
based search was performed. Randomised trials comparing RFA plus TACE and RFA
alone for treatment of HCC were included in this meta-analysis. The outcome of
interest for our analysis was survival (recurrence-free survival and overall
survival). RESULTS: Eight trials with 648 patients were eligible for this meta
analysis. Our pooled results suggest that RFA plus TACE is associated with a
significant advantage in recurrence-free survival (RFS) (HR=0.58; 95% CI=0.42
0.80, P=0.001), and overall survival (OS) (HR=0.60; 95% CI=0.47-0.76, P<0.001).
CONCLUSION: TACE combined with RFA was more effective than RFA alone, especially
for treatment for intermediate and large-size hepatic tumours or younger patients
with HCC.
PMID- 26428662
TI - Survey of Neurological Disorders in Children Aged 9-15 Years in Northern India.
AB - The prevalence of neurological disorders in resource-poor settings, although
likely to be high, is largely unexplored. The prevalence and risk factors for
neurological disorders, including epilepsy and intellectual, motor, vision, and
hearing deficits, in children aged 9 to 15 years in the community were
investigated. A new instrument was developed, validated, and used in a 2-stage
community survey for neurological disorders in Lucknow, India. Screen-positives
and random proportion of screen-negatives were validated using predefined
criteria. Prevalence of different neurological disorders was calculated by
weighted proportions. Of 6431 children screened, 221 were positive. A total of
214 screen-positives and 251 screen-negatives were validated. Prevalence of
neurological disorders was 31.3 per 1000 children of this age group (weighted 95%
confidence interval = 16.5, 46.4). The final model for risk factors included age,
mud house, delayed cry at birth, and previous head injury. The prevalence of
neurological disorders is high in this region. Predictors of neurological
disorders are largely modifiable.
PMID- 26428663
TI - The Val142Ile transthyretin cardiac amyloidosis: not only an Afro-American
pathogenic variant? A single-centre Italian experience.
AB - Transthyterin amyloidosis is a life-threatening disorder caused by the deposition
of hepatocyte-derived transthyretin (TTR) amyloid in various tissues and organs.
The most common worldwide pathogenic variant with almost exclusive cardiac
involvement is Val142Ile with an allele frequency of 3.5% in U.S. African
American population, but supposed extremely rare, with only sporadic cases in
Caucasian patients. Unexpectedly, in our amyloidosis referral centre, we
identified five patients (15.1% of all TTRm diagnosed patients, three families,
two singleton) with Val142Ile variant belonging to unrelated families of
Caucasian origin. Molecular study was performed in a total of 10 individuals of
which three were Italian families (three affected individuals and five unaffected
individuals) and two were singleton (one Italian patient and one patient from
Argentine with Spanish ancestry). Sequence analysis of TTR gene revealed the
presence of the heterozygous Val142Ile in the five affected patients and in five
asymptomatic individuals. All probands underwent, at diagnosis, a complete
clinical, echocardiographic and biohumoral evaluation. To the best of our
knowledge, we describe the larger report of Caucasian patients with Val142Ile
cardiomyopathy. All patients at diagnosis showed symptoms of heart failure with
increased thickness of left ventricular walls and systo-diastolic left
ventricular dysfunction. They also showed increased plasma values of NT-proBNP
and troponin I. Our data confirm that Caucasian patients with the Val142Ile
pathogenic variant have phenotypic manifestations similar to that of African
American one. Moreover, our data clearly show that Val142Ile pathogenic variant
is not only an African-American mutation but could be also an underestimated
Caucasian variant.
PMID- 26428661
TI - Gastric cancer stem cells: evidence, potential markers, and clinical
implications.
AB - Gastric cancer is a significant global health problem. It is the fifth most
common cancer and third leading cause of cancer-related death worldwide (Torre et
al. in CA Cancer J Clin 65(2):87-108, 2015). Despite advances in treatment,
overall prognosis remains poor, due to tumour relapse and metastasis. There is an
urgent need for novel therapeutic approaches to improve clinical outcomes in
gastric cancer. The cancer stem cell (CSC) model has been proposed to explain the
high rate of relapse and subsequent resistance of cancer to current systemic
treatments (Vermeulen et al. in Lancet Oncol 13(2):e83-e89, 2012). CSCs have been
identified in many solid malignancies, including gastric cancer, and have
significant clinical implications, as targeting the CSC population may be
essential in preventing the recurrence and spread of a tumour (Dewi et al. in J
Gastroenterol 46(10):1145-1157, 2011). This review seeks to summarise the current
evidence for CSC in gastric cancer, with an emphasis on candidate CSC markers,
clinical implications, and potential therapeutic approaches.
PMID- 26428664
TI - The small chemical enzyme inhibitor 5-phenylnicotinic acid/CD13 inhibits cell
migration and invasion of tartrate-resistant acid phosphatase/ACP5-overexpressing
MDA-MB-231 breast cancer cells.
AB - Tartrate-resistant acid phosphatase (TRAP/ACP5/uteroferrin/purple acid
phosphatase/PP5) has received considerable attention as a newly discovered
proinvasion metastasis driver associated with different malignancies. This
renders TRAP an interesting target for novel anti-cancer therapy approaches. TRAP
exists as two isoforms, 5a and 5b, where the 5a isoform represents an
enzymatically less active monomeric precursor to the more enzymatically active 5b
isoform generated by proteolytic excision of a repressive loop domain. Recently,
three novel lead compounds were identified by fragment-based screening and
demonstrated to be efficient TRAP enzyme inhibitors in vitro. We conclude that
one of the three compounds i.e. 5-phenylnicotinic acid (CD13) was efficient as a
TRAP inhibitor with Kic values in the low micromolar range towards the TRAP 5b
isoform, but was not able to inhibit the TRAP 5a isoform. Structure-based docking
revealed similar interactions of CD13 with the active site in both TRAP isoforms.
In stably TRAP-overexpressing MDA-MB-231 breast cancer cells, CD13 inhibited
intracellular TRAP activity and showed no cytotoxicity at 200 uM. Furthermore,
CD13 selectively blocked the TRAP 5b isoform compared to the TRAP 5a in cultured
cells, indicating the usefulness of CD13 for assessing the different biological
functions of the two TRAP isoforms 5a and 5b in cell systems. Moreover,
inhibition of cell migration and invasion of stably TRAP-overexpressing MDA-MB
231 by CD13 was observed. These data establish a proof of principle that a small
chemical inhibitor of the TRAP enzyme can block TRAP-dependent functions in
cancer cells.
PMID- 26428665
TI - HSPA12B regulates SSeCKS-mediated astrocyte inflammatory activation in
neuroinflammation.
AB - Reactive astrocytosis has been considered either beneficial or detrimental
effection in neuroinflammatory disease. HSPA12B, a new member belongs to the 70
kDa family of heat shock proteins (HSP70) which could modulate inflammatory
response, also shows an connection with the astrocyte activation. Recently, it
was reported that Src-Suppressed-C Kinase Substrate (SSeCKS) was detected in heat
shock protein A12B (HSPA12B) interacting proteins using a yeast 2-hybrid system.
SSeCKS, a major Lipopolysaccharide (LPS) response protein, has been involved in
regulating astrocyte activation via production of proinflammatory factor in CNS
inflammation. In this study, we found HSPA12B might regulate the expression and
activity of SSeCKS to promote astrocyte inflammatory activation and release of
inflammatory mediators, such as TNF-alpha and IL-1beta in spinal cord primary
astroglial cultures exposed to LPS treatment. The promoting mechanism of
interaction between HSPA12B and SSeCKS on LPS-induced astrocyte activation was
mediated via the activation of JNK and p38 signaling pathways but not ERK1/2 MAPK
signaling pathway. HSPA12B binded to SSeCKS via its both N terminus consisted of
amino acids 1-330 and C terminus consisted of amino acids 1278-1596. And, in
vivo, we confirmed the interaction between HSPA12B and SSeCKS of astrocyte
activation in the pathogenesis of EAE. The regulatory mechanisms of HSPA12B
SSeCKS interaction may possibly be the key therapeutic strategy of
neuroinflammatory disease.
PMID- 26428667
TI - Dynamic risk control by human nucleus accumbens.
AB - Real-world decisions about reward often involve a complex counterbalance of risk
and value. Although the nucleus accumbens has been implicated in the underlying
neural substrate, its criticality to human behaviour remains an open question,
best addressed with interventional methodology that probes the behavioural
consequences of focal neural modulation. Combining a psychometric index of risky
decision-making with transient electrical modulation of the nucleus accumbens,
here we reveal profound, highly dynamic alteration of the relation between
probability of reward and choice during therapeutic deep brain stimulation in
four patients with treatment-resistant psychiatric disease. Short-lived phasic
electrical stimulation of the region of the nucleus accumbens dynamically altered
risk behaviour, transiently shifting the psychometric function towards more risky
decisions only for the duration of stimulation. A critical, on-line role of human
nucleus accumbens in dynamic risk control is thereby established.
PMID- 26428666
TI - Different definitions of neurodegeneration produce similar
amyloid/neurodegeneration biomarker group findings.
AB - We recently demonstrated that the frequencies of biomarker groups defined by the
presence or absence of both amyloidosis (A+) and neurodegeneration (N+) changed
dramatically by age in cognitively non-impaired subjects. Our present objectives
were to assess the consequences of defining neurodegeneration in five different
ways on the frequency of subjects classified as N+, on the demographic
associations with N+, and on amyloidosis and neurodegeneration (A/N) biomarker
group frequencies by age. This was a largely cross-sectional observational study
of 1331 cognitively non-impaired subjects aged 50-89 drawn from a population
based study of cognitive ageing. We assessed demographic associations with N+,
and A/N biomarker group frequencies by age where A+ was defined by amyloid PET
and N+ was defined in five different ways: (i) abnormal adjusted hippocampal
volume alone; (ii) abnormal Alzheimer's disease signature cortical thickness
alone; (iii) abnormal fluorodeoxyglucose positron emission tomography alone; (iv)
abnormal adjusted hippocampal volume or abnormal fluorodeoxyglucose positron
emission tomography; and (v) abnormal Alzheimer's disease signature cortical
thickness or abnormal fluorodeoxyglucose positron emission tomography. For each
N+ definition, participants were assigned to one of four biomarker groups; A-N-,
A+N-, A-N+, or A+N+. The three continuous individual neurodegeneration measures
were moderately correlated (rs = 0.42 to 0.54) but when classified as normal or
abnormal had only weak agreement (kappa = 0.20 to 0.29). The adjusted hippocampal
volume alone definition classified the fewest subjects as N+ while the
Alzheimer's disease signature cortical thickness or abnormal fluorodeoxyglucose
positron emission tomography definition classified the most as N+. Across all N+
definitions, N+ subjects tended to be older, more often male and APOE4 carriers,
and performed less well on functional status and learning and memory than N-
subjects. For all definitions of neurodegeneration, (i) the frequency of A-N- was
100% at age 50 and declined monotonically thereafter; (ii) the frequency of A+N-
increased from age 50 to a maximum in the mid-70s and declined thereafter; and3
(iii) the frequency of A-N+ (suspected non-Alzheimer's pathophysiology) and of
A+N+ increased monotonically beginning in the mid-50s and mid-60s, respectively.
Overall, different neurodegeneration measures provide similar but not completely
redundant information. Despite quantitative differences, the overall qualitative
pattern of the A-N-, A+N-, A-N+, and A+N+ biomarker group frequency curves by age
were similar across the five different definitions of neurodegeneration. We
conclude that grouping subjects by amyloidosis and neurodegeneration status
(normal/abnormal) is robust to different imaging definitions of neurodegeneration
and thus is a useful way for investigators throughout the field to communicate in
a common classification framework.
PMID- 26428668
TI - Depression and Psychosocial Risk Factors among Community-Dwelling Older Adults in
Singapore.
AB - Depression is the most common mental and emotional disorder that emerges in the
late stages of life. It is closely associated with poor health, disability,
mortality, and suicide. The study examines the risk factors of depression in late
life, especially the psychosocial factors, among a sample comprising 162
community-dwelling Singaporean adults aged 65 years and above. An interview-based
structured survey was conducted in multiple senior activity centers located in
different parts of Singapore. Results from the hierarchical regression analysis
show that 32.9% of the variance in geriatric depression can be explained by the
three psychosocial factors, among which loneliness, perceived social support, and
the emotional regulation component of resilience are significantly associated
with depression in older adults. Large-scale studies should be conducted to
confirm the findings of the present study, and to further examine the predictive
effects of these psychosocial factors on depression among older adults.
PMID- 26428669
TI - A continuous mapping between space and valence with left- and right-handers.
AB - In this research, we examined whether emotional valence could correspond to a
continuous lateral bias in space, according to a mental metaphor that establishes
the mapping between a concrete domain (space) and an abstract one (valence).
Because acting with one's dominant hand is associated with fluency and positive
valence (the bodily specificity hypothesis, or BSH), we asked strong right- and
left-handers to perform two spatial location tasks using emotional faces with
seven levels of valence. We hypothesized and showed through two studies that,
according to the BSH, extreme valenced stimuli (as compared to moderate and weak
ones) would be located more at the extremity of a horizontal line, according to
the correspondences between handedness and the different valences of the stimuli.
This research establishes that spatial and continuous mapping of emotions was
obtained while controlling for motivational direction.
PMID- 26428671
TI - Liposome Formation Using a Coaxial Turbulent Jet in Co-Flow.
AB - PURPOSE: Liposomes are robust drug delivery systems that have been developed into
FDA-approved drug products for several pharmaceutical indications. Direct control
in producing liposomes of a particular particle size and particle size
distribution is extremely important since liposome size may impact cellular
uptake and biodistribution. METHODS: A device consisting of an injection-port was
fabricated to form a coaxial turbulent jet in co-flow that produces liposomes via
the ethanol injection method. By altering the injection-port dimensions and flow
rates, a fluid flow profile (i.e., flow velocity ratio vs. Reynolds number) was
plotted and associated with the polydispersity index of liposomes. RESULTS:
Certain flow conditions produced unilamellar, monodispersed liposomes and the
mean particle size was controllable from 25 up to >465 nm. The mean liposome size
is highly dependent on the Reynolds number of the mixed ethanol/aqueous phase and
independent of the flow velocity ratio. CONCLUSIONS: The significance of this
work is that the Reynolds number is predictive of the liposome particle size,
independent of the injection-port dimensions. In addition, a new model describing
liposome formation is outlined. The significance of the model is that it relates
fluid dynamic properties and lipid-molecule physical properties to the final
liposome size.
PMID- 26428670
TI - What a car does to your perception: Distance evaluations differ from within and
outside of a car.
AB - Almost a century ago it was first suggested that cars can be interpreted as
tools, but consequences of this assumption were never tested. Research on hand
held tools that are used to manipulate objects in the environment suggests that
perception of near space is extended by using tools. Literature on environment
perception finds perception of far space to be modulated by the observer's
potential to act in the environment. Here we argue that a car increases the
action potential and modulates perception of far space in a way similar to how
hand-held tools modulate perception of near space. Five distances (4 to 20
meters) were estimated by pedestrians and drivers before and after
driving/walking. Drivers underestimated all distances to a larger percentage than
did pedestrians. Underestimation was even stronger after driving. We conclude
that cars modulate the perception of far distances because they modulate the
driver's perception, like a tool typically does, and change the perceived action
potential.
PMID- 26428672
TI - Understanding the cholesterol metabolism-perturbing effects of docosahexaenoic
acid by gas chromatography-mass spectrometry targeted metabonomic profiling.
AB - PURPOSE: Over the past few decades, docosahexaenoic acid (DHA) has gained special
attention for management of cholesterol-associated metabolic disorders and
neurodegenerative diseases such as Alzheimer's disease (AD) owing to its
neuroprotective, anti-inflammatory and hypolipidemic properties. Several
epidemiological studies have reported the effect of DHA in reducing the risk of
developing AD by lowering cholesterol. Hypercholesterolemia is a pro
amyloidogenic factor influencing the enzymatic processing of amyloid-beta
precursor protein (AbetaPP) to toxic beta-amyloid. However, the mechanism by
which DHA modulates the cholesterol pathway has not been established. Thus, the
objective of this study was to investigate the mechanism of regulation of
cholesterol metabolism by DHA in an AbetaPP695 overexpressing AD cell model.
METHODS: A gas chromatography/mass spectrometry method was developed and
validated for the targeted profiling of 11 cholesterol metabolites in DHA-treated
Chinese hamster ovary wild-type (CHO-wt) and AbetaPP695 overexpressing (CHO
AbetaPP695) cells. The differential metabolite profiles between DHA- and vehicle
treated groups were further analyzed using fold change values of the ratio of
concentration of metabolites in CHO-AbetaPP695 to CHO-wt cells. Effect of DHA on
key rate-limiting enzymatic activities within the cholesterol pathway was
established using biochemical assays. RESULTS: Our results showed that DHA
reduced the levels of key cholesterol anabolites and catabolites in CHO
AbetaPP695 cells as compared to CHO-wt cells. Further enzymatic studies revealed
that the cholesterol-lowering effect of DHA was mediated by regulating HMG-CoA
reductase and squalene epoxidase enzyme activities. CONCLUSION: We demonstrate
for the first time the dual effects of DHA in inhibiting HMG-CoA reductase and
squalene epoxidase and modulating the sterol biosynthesis axis of the cholesterol
pathway in AbetaPP695 overexpressing AD. Our novel findings underscore the
potential of DHA as a multi-target hypocholesterolemic agent for the prophylaxis
of AD and other cholesterol-associated diseases.
PMID- 26428674
TI - Regional right ventricular dysfunction in acute pulmonary embolism: relationship
with clot burden and biomarker profile.
AB - Regional right ventricular (RV) dysfunction (RRVD) is an echocardiographic
feature in acute pulmonary embolism (PE), primarily reported in patients with
moderate-to-severe RV dysfunction. This study investigated the clinical
importance of RRVD by assessing its relationship with clot burden and biomarkers.
We identified consecutive patients admitted to the emergency department between
1999 and 2014 who underwent computed tomographic angiography, echocardiography,
and biomarker testing (troponin and NT-proBNP) for suspected acute PE. RRVD was
defined as normal excursion of the apex contrasting with hypokinesis of the mid
free wall segment. RV assessment included measurements of ventricular dimensions,
fractional area change, free-wall longitudinal strain and tricuspid annular plane
systolic excursion. Clot burden was assessed using the modified Miller score. Of
82 patients identified, 51 had acute PE (mean age 66 +/- 17 years, 43% male). No
patient had RV myocardial infarction. RRVD was present in 41% of PEs and absent
in all patients without PE. Among patients with PE, 86% of patients with RRVD had
central or multi-lobar PE. Patients with RRVD had higher prevalence of moderate
to-severe RV dilation (81 vs. 30%, p < 0.01) and dysfunction (86 vs. 23%, p <
0.01). There was a strong trend for higher troponin level in PE patients with
RRVD (38 vs. 13% in PE patients without RRVD, p = 0.08), while there was no
significant difference for NT-proBNP (67 vs. 73%, p = 0.88). RRVD showed good
concordance between readers (87%). RRVD is associated with an increased clot
burden in acute PE and is more prevalent among patients with moderate-to-severe
RV enlargement and dysfunction.
PMID- 26428673
TI - Resveratrol attenuates norepinephrine-induced ovarian cancer invasiveness through
downregulating hTERT expression.
AB - Stress hormone norepinephrine (NE) has been associated with acquisition of cancer
progression, and naturally occurring phytoalexin resveratrol (REV) has been known
to suppress cancer growth and progression. In the present study, we determine the
effect of REV on NE-induced ovarian cancer invasiveness. Pretreatment of REV
significantly inhibited NE-induced ovarian cancer cell epithelial-to-mesenchymal
transition with concomitant recovery of E-cadherin expression. In addition, our
data showed that REV downregulates NE-induced human telomerase reverse
transcriptase (hTERT) expression through inhibiting Src phosphorylation and HIF
1alpha expression. Further, REV reduced NE-induced Slug expression and subsequent
ovarian cancer invasion. More importantly, combined treatment of REV with a
pharmacological inhibitor of beta adrenergic receptor significantly attenuated NE
induced ovarian cancer invasion compared to single treatment. Therefore, we
demonstrate interference of a Src and HIF-1alpha/hTERT/Slug signaling cascade by
REV, providing potential therapeutic targets and inhibition of ovarian cancer.
PMID- 26428675
TI - Bioimpedance analysis versus lung ultrasonography for optimal risk prediction in
hemodialysis patients.
AB - Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients.
Two bedside methods are increasingly utilized to evaluate objectively fluid
status-bioimpedance and lung ultrasonography, but there is no available direct,
head-to-head comparison of their prognostic significance. Importantly, their
predictive abilities have never been tested in a HD population, alongside those
of a classic model that also incorporates established echocardiographic
parameters of increased mortality risk. Between 26 May 2011 and 26 October 2012,
we included in the study 173 patients undergoing chronic HD treatment for at
least 3 months in a single dialysis unit. Relative fluid overload (RFO) and B
lines score (BLS) were used as candidate predictors. From Cox survival analysis
we evaluated the increase in the predictive abilities for all-cause mortality of
adding continuous RFO or BLS to a model including conventional predictors . 31
patients (17.9 %) died during a median follow-up of 21.3 (interquartile range
19.9-30.3) months. All Cox models showed good calibration. The C statistic for
the all-cause mortality prediction increased significantly when the RFO was
included into the baseline model (DeltaC statistics 0.058 95 %CI = 0.003-0.114),
but not when the BLS was included into the baseline model. Only the model that
incorporated RFO showed significantly better risk reclassification abilities than
the baseline model (IDI = 3.6 % and continuous NRI = 24.8 %). Fluid overload, as
assessed by bioimpedance, and not by lung ultrasonography, improves risk
prediction for death, beyond classical and echocardiographic-based risk
prediction scores/parameters.
PMID- 26428676
TI - Relationship between left ventricular mass and coronary artery disease in young
adults: a single-center study using cardiac computed tomography.
AB - We evaluated the relationship between coronary artery disease (CAD) and left
ventricular mass (LVM) as measured by cardiac computed tomography (CT) in young
adults <=40 years of age. We retrospectively enrolled 490 consecutive individuals
(383 males; mean age, 35.2 +/- 4.4 years) who underwent cardiac CT. CAD was
defined by the presence of any plaque detected by coronary CT angiography. Left
ventricular (LV) function, including LVM, was automatically measured by a
dedicated workstation. LVM and LVM index (LVMi) in patients with CT-detected CAD
were compared to those of patients without CT-detected CAD. Logistic regression
analysis was used to evaluate the relationship between cardiovascular risk
factors and CAD. Fifty-five individuals had CT-detected CAD (11.2 %, 53 males).
LVM measured by cardiac CT was 126.9 +/- 30.0 g for males and 93.6 +/- 20.9 g for
females. LVM was higher (117.8 +/- 30.8 vs. 133.6 +/- 33.1 g, P < 0.001) in
patients with CT-detected CAD compared with patients without CT-detected CAD.
Obesity, hypertension, smoking, hypercholesterolemia, LVM and LVMi were
predictors of CT-detected CAD. Body mass index (r = 0.237, P < 0.001) and
systolic blood pressure (r = 0.281, P < 0.001) were positively correlated with
LVM. In the multivariate analysis, LVM [odds ratio (OR) = 1.016] and LVMi (OR =
1.026) remained independent predictors of CAD. LVM and LVMi in patients with CT
detected CAD were higher than that of patients without CT-detected CAD. LVM and
LVMi measured by cardiac CT were independent predictors of CAD.
PMID- 26428677
TI - Real-time in vivo imaging reveals the ability of neutrophils to remove
Cryptococcus neoformans directly from the brain vasculature.
AB - Although neutrophils are typically the first immune cells attracted to an
infection site, little is known about how neutrophils dynamically interact with
invading pathogens in vivo. Here, with the use of intravital microscopy, we
demonstrate that neutrophils migrate to the arrested Cryptococcus neoformans, a
leading agent to cause meningoencephalitis, in the brain microvasculature.
Following interactions with C. neoformans, neutrophils were seen to internalize
the organism and then circulate back into the bloodstream, resulting in a direct
removal of the organism from the endothelial surface before its transmigration
into the brain parenchyma. C. neoformans infection led to enhanced expression of
adhesion molecules macrophage 1 antigen on neutrophils and ICAM-1 on brain
endothelial cells. Depletion of neutrophils enhanced the brain fungal burden.
Complement C3 was critically involved in the recognition of C. neoformans by
neutrophils and subsequent clearance of the organism from the brain. Together,
our finding of the direct removal of C. neoformans by neutrophils from its
arrested site may represent a novel mechanism of host defense in the brain, in
addition to the known, direct killing of microorganisms at the infection sites.
These data are the first to characterize directly the dynamic interactions of
leukocytes with a microbe in the brain of a living animal.
PMID- 26428678
TI - gammadelta T cells protect against LPS-induced lung injury.
AB - gammadelta T lymphocytes are a unique T cell population with important anti
inflammatory capabilities. Their role in acute lung injury, however, is poorly
understood but may provide significant insight into lung-protective mechanisms
occurring after injury. In a murine model of lung injury, wild-type C57BL/6 and
TCRdelta(-/-) mice were exposed to Escherichia coli LPS, followed by analysis of
gammadelta T cell and macrophage subsets. In the absence of gammadelta T cells,
TCRdelta(-/-) mice developed increased inflammation and alveolar-capillary leak
compared with wild-type C57BL/6 mice after LPS exposure that correlated with
expansion of distinct macrophage populations. Classically activated M1
macrophages were increased in the lung of TCRdelta(-/-) mice at d 1, 4, and 7
after LPS exposure that peaked at d 4 and persisted at d 7 compared with wild
type animals. In response to LPS, Vgamma1 and Vgamma7 gammadelta T cells were
expanded in the lung and expressed IL-4. Coculture experiments showed decreased
expression of TNF-alpha by resident alveolar macrophages in the presence of
gammadelta T cells that was reversed in the presence of an anti-IL-4-blocking
antibody. Treatment of mice with rIL4 resulted in reduced numbers of M1
macrophages, inflammation, and alveolar-capillary leak. Therefore, one mechanism
by which Vgamma1 and Vgamma7 gammadelta T cells protect against LPS-induced lung
injury is through IL-4 expression, which decreases TNF-alpha production by
resident alveolar macrophages, thus reducing accumulation of M1 macrophages,
inflammation, and alveolar-capillary leak.
PMID- 26428679
TI - Characterization of lung infection-induced TCRgammadelta T cell phenotypes by
CyTOF mass cytometry.
AB - T cell receptor gammadelta cells are known to be the primary effector T cells
involved in the response to bacterial infections, yet their phenotypic
characteristics are not as well established as other T cell subsets. In this
study, we used cytometry by time-of-flight mass cytometry to better characterize
the phenotypic response of T cell receptor gammadelta cells to Streptococcus
pneumoniae lung infection. Mice were infected, and cells from lung washouts,
spleen, and lymph nodes were stained to detect cell-surface, intracellular, and
signaling markers. We observed that infection caused a significant increase in T
cell receptor gammadelta cells, which expressed high interferon-gamma and
interleukin-17A levels. Profiling T cell receptor gammadelta cells by cytometry
by time-of-flight revealed that activated gammadelta T cells uniquely coexpressed
cell-surface Gr-1, cluster of differentiation 14, and cluster of differentiation
274 (programmed death-ligand 1). Further classification of Gr-1 expression
patterns on T cell receptor gammadelta cells demonstrated that Gr-1(+) T cell
receptor gammadelta cells were the primary source of interferon-gamma, whereas Gr
1(-) cells mostly expressed interleukin-17A. Gr-1(+) T cell receptor gammadelta
cells also showed higher zeta-chain-associated protein kinase 70, p38, and 4eBP1
signaling in response to infection as compared with Gr-1(-) T cell receptor
gammadelta cells. Taken together, Gr-1 expression patterns on gammadelta T cells
in the lung provide a robust marker to differentiate interferon-gamma- and
interleukin-17A-producing subsets involved in the early immune response to
bacterial pneumonia.
PMID- 26428680
TI - Cochlear implant in a patient with neurofibromatosis type 2 undergoing
radiotherapy.
PMID- 26428681
TI - Anti-endotoxin effects of terpenoids fraction from Hygrophila auriculata in
lipopolysaccharide-induced septic shock in rats.
AB - CONTEXT: Hygrophila auriculata (K. Schum) Heine (Acanthaceae) has been
traditionally used for the treatment of various ailments such as inflammation,
rheumatism, jaundice and malaria. OBJECTIVE: The present study aims to separate
terpenoid fraction (TF) from alcohol (70%) extract of the whole plant of
Hygrophila auriculata and assess its anti-inflammatory activity. MATERIALS AND
METHODS: HPTLC analysis of TF was performed for the estimation of lupeol. Edema
was induced in Wistar albino rats by subplanter injection of 0.1 ml of 1% (w/v)
carrageenan into the right hind paw after 1 h of TF administration (100 and 200
mg/kg oral). Septic shock was induced by intraperitoneal administration of LPS
(100 MUg/kg) in rats and interleukins (IL-1beta and IL-6), tumor necrosis factor
(TNF-alpha), superoxide dismutase (SOD), lipid peroxidation (LPO), and nitric
oxide (NO) were measured in serum. AutoDock 4.2 was used for molecular docking.
RESULTS: Administration of TF significantly (p < 0.005) restored the serum levels
of cytokines, LPO (7.77 +/- 0.034 versus 4.59 +/- 0.059 nmole of TBARS), NO (9.72
+/- 0.18 versus 4.15 +/- 0.23 umol nitrite/mg of wet tissue), and SOD (4.89 +/-
0.036 versus 7.83 +/- 0.033 Unit/mg protein) compared with the LPS-challenged
rats. Analysis of in silico results revealed that TNF-alpha is the most
appropriate target in eliciting anti-inflammatory activity. CONCLUSION: The
present findings suggest that TF of Hygrophila auriculata possesses great promise
as an anti-inflammatory agent which may be due to its antioxidant effect.
Molecular docking results could be exploited for lead optimization and
development of suitable treatment of inflammatory disorders.
PMID- 26428685
TI - The ability of 18F-choline PET/CT to identify local recurrence of prostate
cancer.
AB - PURPOSE: To determine when 18F-choline PET/CT can truly identify local recurrence
of prostate cancer. METHODS: 1031 patients from 3 European centers underwent
(18)F-choline PET/CT (FCH PET/CT) for recurrent disease; 131 subjects (12.7%)
showed a positive FCH uptake in the prostatic gland or prostatic fossa. Median
age was 72 years (range 48-87 years), and the median PSA level at the time of FCH
PET/CT scan was 4.41 ng/mL (0.22-18.13 ng/mL). 45 patients (34.4%) had a Gleason
score (GS) >7, and the residual subjects had a GS <= 7. The assessment of true or
false-positive FCH PET/CT findings was made by magnetic resonance imaging (n =
34) and/or biopsy in 75/131 cases. A chi (2) test and a Z Kolmogorov-Smirnov test
were used to assess the correlation between clinical variables (age, PSA, GS,
type of therapy) and FCH PET/CT findings. RESULTS: FCH PET/CT resulted truly
positive (TP) for recurrent disease in the prostatic gland/fossa in 59/75
patients (79%) and falsely positive (FP) in 16 subjects (21%). The median value
of PSA at the time of FCH PET/CT scan was higher in TP as compared to FP,
although not statistically significant (4.76 vs. 3.04 ng/mL p > 0.05). Similarly,
median age, GS categories, and the type of therapy were similar between the two
groups (p > 0.05). However, when matching GS categories and PSA values, we found
that the number of patients with TP findings were higher in the case of a PSA > 2
ng/mL, independently from the GS (ranging between 74% and 92%). Conversely, FP
rate ranged between 50% and 65% in patients with a PSA <= 2 ng/mL, especially in
the case of GS <= 7, whereas FP was around 25% in those with a GS >7 and PSA > 2
ng/mL. CONCLUSIONS: FCH PET/CT has a limited role in evaluation of prostatic
gland/fossa recurrence, due to the physiological biodistribution of the
radiopharmaceutical agent. However, in 70-90% of patients with a PSA >2 ng/mL,
independently from GS, a focal FCH uptake is compatible with a true local
recurrence.
PMID- 26428686
TI - Chronobiology and Pharmacologic Modulation of the Renin-Angiotensin-Aldosterone
System in Dogs: What Have We Learned?
AB - Congestive heart failure (CHF) is a primary cause of morbidity and mortality with
an increasing prevalence in human and canine populations. Recognition of the role
of renin-angiotensin-aldosterone system (RAAS) overactivation in the
pathophysiology of CHF has led to significant medical advances. By decreasing
systemic vascular resistance and angiotensin II (AII) production, angiotensin
converting enzyme (ACE) inhibitors such as benazepril improve cardiac
hemodynamics and reduce mortality in human and dog CHF patients. Although several
experiments have pointed out that efficacy of ACE inhibitors depends on the time
of administration, little attention is paid to the optimum time of dosing of
these medications. A thorough characterization of the chronobiology of the renin
cascade has the potential to streamline the therapeutic management of RAAS
related diseases and to help determining the optimal time of drug administration
that maximizes efficacy of ACE inhibitors, while minimizing the occurrence of
adverse effects. We have developed an integrated pharmacokinetic-pharmacodynamic
model that adequately captures the disposition kinetics of the paradigm drug
benazeprilat, as well as the time-varying changes of systemic renin-angiotensin
aldosterone biomarkers, without and with ACE inhibition therapy. Based on these
chronobiological investigations, the optimal efficacy of ACE inhibitors is
expected with bedtime dosing. The data further show that benazepril influences
the dynamics of the renin-angiotensin-aldosterone cascade, resulting in a
profound decrease in AII and aldosterone (ALD), while increasing renin activity
for about 24 h. From the results of recent investigations in human, it is
hypothesized that reduction of AII and ALD is one of the drivers of increased
survival and improved quality of life in dogs receiving ACE inhibitors. To
support and consolidate this hypothesis, additional efforts should be directed
toward the collection of circulating RAAS peptides in spontaneous cases of canine
CHF. If such a link could be established, profiling of these biomarkers could
support determination of the severity of heart failure, complement clinical and
echocardiographic findings, and be used for therapeutic drug monitoring purposes.
PMID- 26428688
TI - Magnetic Transitions in Iron Porphyrin Halides by Inelastic Neutron Scattering
and Ab Initio Studies of Zero-Field Splittings.
AB - Zero-field splitting (ZFS) parameters of nondeuterated metalloporphyrins
[Fe(TPP)X] (X = F, Br, I; H2TPP = tetraphenylporphyrin) have been directly
determined by inelastic neutron scattering (INS). The ZFS values are D = 4.49(9)
cm-1 for tetragonal polycrystalline [Fe(TPP)F], and D = 8.8(2) cm-1, E = 0.1(2)
cm-1 and D = 13.4(6) cm-1, E = 0.3(6) cm-1 for monoclinic polycrystalline
[Fe(TPP)Br] and [Fe(TPP)I], respectively. Along with our recent report of the ZFS
value of D = 6.33(8) cm-1 for tetragonal polycrystalline [Fe(TPP)Cl], these data
provide a rare, complete determination of ZFS parameters in a metalloporphyrin
halide series. The electronic structure of [Fe(TPP)X] (X = F, Cl, Br, I) has been
studied by multireference ab initio methods: the complete active space self
consistent field (CASSCF) and the N-electron valence perturbation theory (NEVPT2)
with the aim of exploring the origin of the large and positive zero-field
splitting D of the 6A1 ground state. D was calculated from wave functions of the
electronic multiplets spanned by the d5 configuration of Fe(III) along with spin
orbit coupling accounted for by quasi degenerate perturbation theory. Results
reproduce trends of D from inelastic neutron scattering data increasing in the
order from F, Cl, Br, to I. A mapping of energy eigenvalues and eigenfunctions of
the S = 3/2 excited states on ligand field theory was used to characterize the
sigma- and pi-antibonding effects decreasing from F to I. This is in agreement
with similar results deduced from ab initio calculations on CrX63- complexes and
also with the spectrochemical series showing a decrease of the ligand field in
the same directions. A correlation is found between the increase of D and
decrease of the pi- and sigma-antibonding energies e(lambda)(X) (lambda = sigma,
pi) in the series from X = F to I. Analysis of this correlation using second
order perturbation theory expressions in terms of angular overlap parameters
rationalizes the experimentally deduced trend. D parameters from CASSCF and
NEVPT2 results have been calibrated against those from the INS data, yielding a
predictive power of these approaches. Methods to improve the quantitative
agreement between ab initio calculated and experimental D and spectroscopic
transitions for high-spin Fe(III) complexes are proposed.
PMID- 26428689
TI - Endoscopic Management of Esophageal Anastomotic Leaks After Surgery for Malignant
Disease.
AB - BACKGROUND: Esophageal anastomotic leaks after cancer surgery remain a major
cause of morbidity and mortality. Endoscopic interventions, including covered
metal stents (cSEMS), clips, and direct percutaneous endoscopic jejunostomy
(dPEJ) tubes are increasingly used despite limited published data regarding their
utility in this setting. This study aimed to determine the efficacy and safety of
a multimodality endoscopic approach to anastomotic leak management after
operation for esophageal or gastric cancer. METHODS: We performed a retrospective
review of prospectively maintained databases of gastric and esophageal operations
at our hospital between January 2003 and December 2012. Included patients had an
operation for esophageal or gastric cancer, demonstrated evidence of an
anastomotic leak at the esophageal anastomosis, and underwent attempted
endoscopic therapy. Healing was defined as clinical and radiographic leak
resolution. RESULTS: Forty-nine patients with leaks underwent endoscopic
management. Of the 49 patients, 31 (63%) received cSEMS, 40 (82%) had dPEJ tubes
inserted, and 3 (6%) received clips. Twenty-three (47%) patients underwent a
combined approach. Overall, 88% of patients achieved healing in a median of 83
days. Twenty-two of 23 patients (96%) who underwent a multimodality endoscopic
approach healed. Only 1 patient had a major complication associated with stent
erosion into the pulmonary artery, which was successfully treated with operative
repair. CONCLUSIONS: Esophageal anastomotic leaks after esophageal and gastric
cancer operations can be managed successfully and safely with endoscopic therapy.
Combining cSEMS for leak control and dPEJ tube placement for nutritional support
was highly effective in achieving healing, without the need for surgical repair.
PMID- 26428690
TI - Nodal Upstaging During Lung Cancer Resection Is Associated With Surgical
Approach.
AB - BACKGROUND: Recent reports indicate that thoracoscopic lobectomy for lung cancer
may be associated with lower rates of surgical upstaging. We queried a statewide
cancer registry for differences in upstaging rates and survival by surgical
approach. METHODS: The Kentucky Cancer Registry (KCR) collects data, including
centralized pathology reporting, on cancer patients treated statewide. We
performed a retrospective review from 2010 to 2012 to examine clinical and
pathologic stage. We assessed rates of upstaging and whether the surgical
approach, thoracotomy (THOR) versus minimally invasive techniques (video-assisted
thoracic surgery; VATS), had an impact on final pathologic stage and survival.
RESULTS: The KCR database from 2010 to 2012 contained information on 2830 lung
cancer cases, 1964 having THOR procedure and 500 having VATS resections.
Preoperatively, 36.4% of THOR were clinically stage 1a versus 47.4% VATS (p =
0.0002). Of these, final pathologic stage remained stage 1a in 30.5% of THOR
procedures and 38.0% of VATS (p = 0.0002). The overall nodal upstaging rate for
THOR was 9.9% and 4.8% for VATS (p = 0.002). Decreased nodal upstaging was found
with VATS, independent of tumor size and extent of resection (odds ratio 0.6, 95%
confidence interval [CI]: 0.387 to 0.985, p = 0.04). However, improved survival
was found with VATS compared with THOR (hazard ratio 0.733, 95% CI: 0.592 to
0.907, p = 0.0042). CONCLUSIONS: Consistent with other reports, we report a lower
upstaging rate with VATS. Nevertheless, there is a survival advantage in VATS
patients. Although selection bias may play a role in these observed differences,
the improved quality of life measures associated with VATS may explain survival
improvement despite lower surgical upstaging.
PMID- 26428691
TI - Anomalous Aortic Origin of a Coronary Artery: Surgical Repair With Anatomic- and
Function-Based Follow-Up.
AB - BACKGROUND: Anomalous aortic origin of the coronary artery (AAOCA) with an
interarterial (IAC) course is an uncommon congenital anomaly. Surgical
indications and repair techniques have evolved. We have managed 259 adult
patients with AAOCA over 40 years. Our management strategy includes anatomic- and
function-based surveillance to select surgical candidates. We reviewed our
surgical cohort and analyzed anatomic and functional outcomes. METHODS: We
queried our heart center databases to obtain the names of all patients with AAOCA
managed at our institution between 1974 and 2014. We performed a retrospective
chart review. RESULTS: Two hundred fifty-nine patients were managed for AAOCA.
Sixty-one underwent surgical intervention. Twenty-six with associated coronary
atherosclerosis were excluded. Thirty-one who underwent surgical repair were
analyzed. Mean age was 42.5 +/- 2.7 years. Twenty-four patients (77.4%) had right
AAOCA. Six (19.4%) had left AAOCA. One (3.2%) had bilateral coronary anomalies.
Repair techniques included 21 unroofing procedures (67.7%), 6 translocations
(19.4%), and 4 coronary artery bypass grafting (CABG) procedures (12.9%). Mean
follow-up was 3.8 +/- 0.8 years. Thirteen patients underwent follow-up anatomic
testing with computed tomography. Twelve of these patients had widely patent
coronary arteries, and 1 patient had mild coronary artery stenosis. Seventeen
patients underwent functional testing. Fifteen of these patients had no evidence
of ischemia. One patient had reversible ischemia after CABG, and 1 had
subclinical ischemia after unroofing. There was 1 late mortality from
endocarditis. CONCLUSIONS: Our multidisciplinary program uses a treatment
algorithm to select patients with AAOCA for surgical intervention. Only a small
subset requires an operation, and we favor unroofing and translocation
techniques. With this paradigm, outcomes are excellent, as validated with
anatomic- and function-based testing.
PMID- 26428693
TI - Kommerell Diverticulum Should Be Removed in Children With Vascular Ring and
Aberrant Left Subclavian Artery.
AB - BACKGROUND: Right aortic arch with aberrant left subclavian artery is the most
frequent cause of vascular ring. Ligamentum arteriosus division opens the ring
but leaves the Kommerell diverticulum in place, with a risk of residual
compression, aneurysmal dilation, dissection, or even rupture. A procedure
consisting of translocation of the aberrant left subclavian artery to the left
carotid artery with removal of the Kommerell diverticulum and division of the
ligamentum is currently advocated. METHODS: Between September /2009 and August
2011, 12 consecutive patients underwent the foregoing procedure. Clinical
findings, surgical procedure, complications, histopathologic findings, and follow
up data were retrospectively analyzed. RESULTS: Mean age at the time of operation
was 7.7 years (median, 4.3 years, range, 0.9 to 18.9 years), and mean weight was
26 kg (median, 18 kg; range, 8.4 to 59 kg). All patients had symptoms. Computed
tomography scan or magnetic resonance imaging, or both, had confirmed the
diagnosis in all patients. Postoperative events, all transient, included
chylothorax (1 patient), phrenic palsy (1 patient), pneumonia (1 patient), and
the need for prolonged chest drainage (3 patients). Mean follow-up reached 19
months (median, 13 months; range, 12 to 41 months). Mild residual respiratory
symptoms were noted in 3 patients. Echo-Doppler analysis showed a patent left
subclavian-to-carotid artery anastomosis. Histopathologic analysis of the
resected diverticulum (n = 6) showed cystic medial necrosis in four diverticula
(focal in one). CONCLUSIONS: Translocation of the aberrant left subclavian artery
with diverticulum resection and ligamentum division is an efficient procedure for
symptom relief. Profound wall abnormalities such as medial necrosis in at least
50% of the analyzed diverticula encourage us to maintain this strategy, to reduce
the risk of aneurysm formation and dissection.
PMID- 26428692
TI - Coxiella burnetii Endocarditis and Aortic Vascular Graft Infection: An
Underrecognized Disease.
AB - BACKGROUND: Q fever is considered endemic worldwide, and endocarditis, or aortic
vascular infection, or both caused by Coxiella burnetii can be a fatal disease.
The importance of surgical intervention has not yet been defined. We performed a
descriptive retrospective study to assess indications for surgical treatment,
timing of treatment, and outcome. METHODS: We studied all patients from the
cardiac surgery department of a large tertiary hospital who underwent valve
surgical procedure due to endocarditis or aortic surgical procedure due to graft
infection. RESULTS: Throughout a 10-year period, we performed a total of 171
procedures due to valve endocarditis and/or vascular infection. In 16 patients
(9.36%) Coxiella burnetii infection was diagnosed. Ten patients had previous
cardiac surgical procedures, 3 had previous aortic surgical procedures, 2 had
preexisting valvular disease, and 1 patient had no previous valve disorder. All
patients received prolonged oral-specific antibiotic therapy under serologic
guidance. In 9 patients antibiotic treatment (doxycycline and hydroxychloroquine)
was started before the surgical procedure (12.4 +/- 37.5 days), and in 7 patients
after the surgical procedure (5.1 +/- 13.5 days). We observed one in-hospital
death (6.25%) and no long-term mortality. The mean follow-up period was 50.5 +/-
34.7 months (range, 2 to 104 months). CONCLUSIONS: In this series surgical
treatment yielded good results for both Q fever endocarditis and vascular graft
infection. No association was found between timing of the surgical procedure and
patients' outcomes.
PMID- 26428696
TI - Crystallization and arrest mechanisms of model colloids.
AB - We performed dynamic simulations of spheres with short-range attractive
interactions for many values of interaction strength and range. Fast
crystallization occurs in a localized region of this parameter space, but the
character of crystallization pathways is not uniform within this region. Pathways
range from one-step, in which a crystal nucleates directly from a gas, to two
step, in which substantial liquid-like clusters form and only subsequently become
crystalline. Crystallization can fail because of slow nucleation from either gas
or liquid, or because of dynamic arrest caused by strong interactions. Arrested
states are characterized by the formation of networks of face-sharing tetrahedra
that can be detected by a local common neighbor analysis.
PMID- 26428694
TI - Influenza A virus preferentially snatches noncoding RNA caps.
AB - Influenza A virus (IAV) lacks the enzyme for adding 5' caps to its RNAs and
snatches the 5' ends of host capped RNAs to prime transcription. Neither the
preference of the host RNA sequences snatched nor the effect of cap-snatching on
host processes is completely defined. Previous studies of influenza cap-snatching
used poly(A)-selected RNAs from infected cells or relied on annotated host genes
to define the snatched host RNAs, and thus lack details on many noncoding host
RNAs including snRNAs, snoRNAs, and promoter-associated capped small (cs)RNAs,
which are made by "paused" Pol II during transcription initiation. In this study,
we used a nonbiased technique, CapSeq, to identify host and viral-capped RNAs
including nonpolyadenylated RNAs in the same samples, and investigated the
substrate-product correlation between the host RNAs and the viral RNAs. We
demonstrated that noncoding host RNAs, particularly U1 and U2, are the preferred
cap-snatching source over mRNAs or pre-mRNAs. We also found that csRNAs are
highly snatched by IAV. Because the functions of csRNAs remain mostly unknown,
especially in somatic cells, our finding reveals that csRNAs at least play roles
in the process of IAV infection. Our findings support a model where nascent RNAs
including csRNAs are the preferred targets for cap-snatching by IAV and raise
questions about how IAV might use snatching preferences to modulate host-mRNA
splicing and transcription.
PMID- 26428695
TI - A conserved charged single alpha-helix with a putative steric role in paraspeckle
formation.
AB - Paraspeckles are subnuclear particles involved in the regulation of mRNA
expression. They are formed by the association of DBHS family proteins and the
NEAT1 long noncoding RNA. Here, we show that a recently identified structural
motif, the charged single alpha-helix, is largely conserved in the DBHS family.
Based on the available structural data and a previously suggested multimerization
scheme of DBHS proteins, we built a structural model of a (PSPC1/NONO)(n)
multimer that might have relevance in paraspeckle formation. Our model contains
an extended coiled-coil region that is followed by and partially overlaps with
the predicted charged single alpha-helix. We suggest that the charged single
alpha-helix can act as an elastic ruler governing the exact positioning of the
dimeric core structures relative to each other during paraspeckle assembly along
the NEAT1 noncoding RNA.
PMID- 26428698
TI - Soluble beta-(1,3)-glucans enhance LPS-induced response in the monocyte
activation test, but inhibit LPS-mediated febrile response in rabbits:
Implications for pyrogenicity tests.
AB - In the present study, we aimed to determine the influence of beta-(1,3)-d-glucans
on the LPS-induced pro-inflammatory cytokine response in the Monocyte Activation
Test (MAT) for pyrogens, and on the LPS-induced febrile response in the Rabbit
Pyrogen Test (RPT), thus evaluating the resulting effect in the outcome of each
test. It was found that beta-(1,3)-d-glucans elicited the production of pro
inflammatory cytokines IL-1beta, IL-6 and TNF-alpha, also known as endogenous
pyrogens, but not enough to classify them as pyrogenic according to MAT. The same
beta-(1,3)-d-glucans samples were non-pyrogenic by RPT. However, beta-(1,3)-d
glucans significantly enhanced the LPS-induced pro-inflammatory cytokines
response in MAT, insomuch that samples containing non-pyrogenic concentrations of
LPS become pyrogenic. On the other hand, beta-(1,3)-d-glucans had no effect on
sub-pyrogenic LPS doses in the RPT, but surprisingly, inhibited the LPS-induced
febrile response of pyrogenic LPS concentrations. Thus, while beta-(1,3)-d
glucans could mask the LPS pyrogenic activity in the RPT, they exerted an
overstimulation of pro-inflammatory cytokines in the MAT. Hence, MAT provides
higher safety since it evidences an unwanted biological response, which is not
completely controlled and is overlooked by the RPT.
PMID- 26428697
TI - Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles increase the SPF
of the association of UVA and UVB filters.
AB - The encapsulation of natural ingredients, such as rutin, can offer improvements
in sun protection effectiveness. This strategy can provide enhanced flavonoid
content and produces an improved bioactive compound with new physical and
functional characteristics. As an alternative to common synthetic-based
sunscreens, rutin-entrapped gelatin nanoparticles (GNPs) were designed and
associated with ethylhexyl dimethyl PABA (EHDP), ethylhexyl methoxycinnamate
(EHMC) and methoxydibenzoylmethane (BMDBM) in sunscreen formulations. The purpose
of this study was to develop rutin-loaded gelatin nanoparticles and characterize
their physicochemical, thermal, functional and safety properties. Rutin-loaded
gelatin nanoparticles increased antioxidant activity by 74% relative to free
rutin (FR) solution. Also, this new ingredient upgraded the Sun Protection Factor
(SPF) by 48%, indicating its potential as a raw material for bioactive
sunscreens. The safety profile indicated that GNPs and glutaraldehyde (GTA)
decreased HaCaT cell viability in a concentration/time-dependent manner. However,
both blank nanoparticles (B-NC) and rutin-loaded nanoparticles (R-NC) had good
performance on skin compatibility tests. These results functionally characterized
rutin-loaded nanoparticles as a safe SPF enhancer in sunscreens, especially in
association with UV filters.
PMID- 26428699
TI - Unfriendly Filter: An Unusual Cause of Hydronephrosis and Hematuria.
AB - A 67-year-old woman was referred to the urology clinic for abdominal pain and
hematuria. Urine analysis showed microscopic hematuria. Computed tomography
urogram revealed a misplaced inferior vena cava (IVC) filter in the right gonadal
vein causing right hydronephrosis. Retrograde pyelography revealed a 3-cm
ureteral narrowing at the level of the IVC filter. A double-J ureteral stent was
placed in the right ureter prior to exploratory laparotomy, which revealed
partial erosion of the IVC filter into the right ureter and a thrombosed right
ovary. The patient underwent a right oophorectomy and removal of the misplaced
IVC filter. Her postoperative course was uncomplicated.
PMID- 26428700
TI - Tunical Outer Layer Plays an Essential Role in Penile Veno-occlusive Mechanism
Evidenced from Electrocautery Effects to the Corpora Cavernosa in Defrosted Human
Cadavers.
AB - OBJECTIVE: To determine the exact anatomical structure for establishing penile
veno-occlusive function, we sought to conduct a hemodynamic study on defrosted
human cadavers. MATERIALS AND METHODS: Thirteen penises were used for this
experiment, and 11 intact penises were allocated into the electrocautery group
(EG, n = 6) and the ligation group (LG, n = 5). A circumcision was made on the
penis to access the veins. Two #19 scalp needles were fixed in the 3 and 9
o'clock positions in the distal penis for colloid infusion and intracavernous
pressure (ICP) monitoring, respectively. For the EG, the deep dorsal vein and
cavernosal vein trunks were freed for 3-5 cm where at least 3 emissary veins were
identified via opening Buck's fascia; these veins underwent electrocautery at 45
watts, while the ICP was maintained at 0, 50, 75, 100, 125, and 150 mmHg,
respectively. For control, venous ligation was made but at the ICP of 150 mmHg. A
tissue block including the emissary vein was then obtained for histological
analysis. RESULTS: Except all in the EG and those whose ICP exceed 125 mmHg in
the EG, the sinusoids of the corpora cavernosa sustained varied fulgurated
fibrosis in every specimen and the severity appeared reversely commensurate with
the ICP regarding sinusoidal clumping and darkish bands (P <.02 and .01
respectively). CONCLUSION: We conclude that the tunica albuginea can prevent the
electrocautery damage to intracavernous sinusoids once the ICP reached a level
corresponding to a rigid erection. The outer tunica plays an essential role in
fulfilling the veno-occlusive mechanism.
PMID- 26428701
TI - Adherence to NICE guidance on glucagon-like peptide-1 receptor agonists among
patients with type 2 diabetes mellitus: an evaluation using the Clinical Practice
Research Datalink.
AB - AIMS: To assess adherence to the UK's National Institute for Health and Care
Excellence (NICE) guidelines for initiating and continuing glucagon-like peptide
1 (GLP-1) receptor agonists in patients with type 2 diabetes (T2DM). RESEARCH
DESIGN AND METHODS: A retrospective cohort study of 7133 primary care patients
>=40 years with a first prescription for a GLP-1 receptor agonist following
publication of NICE guideline/guidance. Patient characteristics and levels of
clinical monitoring were assessed using descriptive analyses. MAIN OUTCOME
MEASURES: Main outcomes were the proportion of patients initiating GLP-1 receptor
agonists as part of NICE-recommended dual- or triple-therapy regimens; the
proportions meeting NICE triple therapy initiation criteria (glycosylated
hemoglobin [HbA1c] >=7.5% and body mass index [BMI] >=35 kg/m(2)) and the
proportions continuing GLP-1 receptor agonist at 6 months according to NICE
recommendations. RESULTS: Mean age at initiating GLP-1 receptor agonists was 58.2
years (SD 9.4), BMI 38.4 kg/m(2) (SD 6.8) and HbA1c 9.2% (SD 3.2%). Overall, only
25% of patients initiated GLP-1 receptor agonists as part of a NICE-recommended
regimen. Of patients initiated on a recommended triple-therapy regimen, 50%
(646/1284) fulfilled both NICE HbA1c and BMI initiation criteria. Approximately
18% (32/174) of patients continuing NICE-recommended dual therapy at 6 months
achieved a 1% reduction in HbA1c and 6.4% (33/515) continuing with NICE
recommended triple therapy achieved NICE's target reductions for both HbA1c and
body weight. About 8% of patients continuing exenatide as triple therapy (N =
243) achieved both targets. CONCLUSIONS: Adherence to NICE guidance for
initiating and continuing GLP-1 receptor agonists is low. However, lack of data
on ethnicity (for assessing NICE's BMI criteria) and on contraindications and/or
hypersensitivity to other diabetes medication in the treatment pathway have
limited our ability to fully assess adherence to GLP-1 prescribing. Further
research is warranted to better understand general practitioners' prescribing
decisions given the cost of prescribing GLP-1 receptor agonists.
PMID- 26428702
TI - Combination therapies for MDS and AML: Does one plus one equal one?
PMID- 26428703
TI - Decision for disclosure: The experiences of Iranian infertile couples undergoing
assisted reproductive donation procedures.
AB - Controversy surrounding disclosure among the recipients of assisted reproductive
donation procedures is escalating worldwide, but little research has been
conducted in this topic. The purpose of this qualitative study was to explore the
experiences of infertile couples undergoing assisted reproductive donation
procedures. In this exploratory qualitative study, 32 patients (nine couples and
14 women) who were candidates to use donor eggs, donor embryos or surrogacy, and
5 members of infertility treatment team including gynaecologists, midwives and
psychologist (total 37) were purposively selected from the Montaserieh
Infertility Research Centre at Mashhad, Iran in 2012 and interviewed using a semi
structured in-depth method. Data were analysed using conventional qualitative
content analysis with MAXqda software. One overarching theme, entitled
'experiencing uncertainty surrounding the disclosure to others' was identified
from the data. This theme contained two subthemes including 'Couples' decisions
to not disclose to others' and 'Couples' decisions to disclose to others'. Five
categories formed the first subtheme, and the second subtheme emerged from four
categories which are discussed in this paper. The main reason for secrecy was
concern over societal negative views about assisted reproductive donation
procedures. This worry deprived the couples from support from family and friends
and as a result requires them to tolerate psychological pressure when using such
procedures.
PMID- 26428711
TI - Genome-wide association analyses reveal complex genetic architecture underlying
natural variation for flowering time in canola.
AB - Optimum flowering time is the key to maximize canola production in order to meet
global demand of vegetable oil, biodiesel and canola-meal. We reveal extensive
variation in flowering time across diverse genotypes of canola under field,
glasshouse and controlled environmental conditions. We conduct a genome-wide
association study and identify 69 single nucleotide polymorphism (SNP) markers
associated with flowering time, which are repeatedly detected across experiments.
Several associated SNPs occur in clusters across the canola genome; seven of them
were detected within 20 Kb regions of a priori candidate genes; FLOWERING LOCUS
T, FRUITFUL, FLOWERING LOCUS C, CONSTANS, FRIGIDA, PHYTOCHROME B and an
additional five SNPs were localized within 14 Kb of a previously identified
quantitative trait loci for flowering time. Expression analyses showed that among
FLC paralogs, BnFLC.A2 accounts for ~23% of natural variation in diverse
accessions. Genome-wide association analysis for FLC expression levels mapped not
only BnFLC.C2 but also other loci that contribute to variation in FLC expression.
In addition to revealing the complex genetic architecture of flowering time
variation, we demonstrate that the identified SNPs can be modelled to predict
flowering time in diverse canola germplasm accurately and hence are suitable for
genomic selection of adaptative traits in canola improvement programmes.
PMID- 26428712
TI - Evaluation of a web-based educational programme on changes in frequency of
nurses' interventions to help smokers quit and reduce second-hand smoke exposure
in China.
AB - AIMS: To evaluate a web-based educational smoking cessation programme on changes
in the frequency of hospital-based nurses' self-reported interventions to help
smokers quit using the 5 As (i.e. Ask, Advise, Assess, Assist, Arrange), to
reduce exposure to second-hand smoke and to change attitudes about nurses'
involvement in tobacco control. BACKGROUND: Few nurses in China support smokers'
quit attempts using evidence-based smoking cessation interventions based on the 5
As. Limited knowledge is a barrier to intervention. Web-based tobacco cessation
programs have the potential to reach a large population of nurses. DESIGN: A
prospective single-group design with pre-, 3- and 6-month follow-up after the
educational programme evaluated the feasibility of conducting web-based
educational programs in two cities in China in 2012-2013. METHODS: Frequency of
interventions was assessed using a valid and reliable web-based survey with a
convenience sample of nurses from eight hospitals in Beijing and Hefei, China.
Generalized linear models, adjusting for age, clinical setting, education and
site were used to determine changes in the consistent (usually/always) use of the
5 As from baseline to 3 and to 6 months. RESULTS: Nurses (N = 1386) had baseline
and/or 3- and 6-month data. At 6 months, nurses were significantly more likely to
Assess, Assist and Arrange for smoking cessation and recommend smoke-free home
environments. There was significant improvement in attitudes about tobacco
control. CONCLUSIONS: Nurses receiving web-based smoking cessation education
significantly increased self-reports of frequency of providing interventions to
patients who smoke, including recommending smoke-free home environments to
support quit attempts.
PMID- 26428713
TI - Re: Risk of ultrasound-detected neonatal brain abnormalities in intrauterine
growth-restricted fetuses born between 28 and 34 weeks' gestation: relationship
with gestational age at birth and fetal Doppler parameters. R. Cruz-Martinez, V.
Tenorio, N. Padilla, F. Crispi, F. Figueras and E. Gratacos. Ultrasound Obstet
Gynecol 2015; 46: 452-459.
PMID- 26428714
TI - Re: Early prediction and aspirin for prevention of pre-eclampsia (EPAPP) study: a
randomized controlled trial. A. O. Odibo, K. R. Goetzinger, L. Odibo and M. G.
Tuuli. Ultrasound Obstet Gynecol 2015; 46: 414-418.
PMID- 26428715
TI - Reply.
PMID- 26428716
TI - Re: Are fetuses that fail to achieve their growth potential at increased risk of
intrapartum compromise?
PMID- 26428717
TI - Ultrafast charge transfer dynamics in supramolecular Pt(II) donor-bridge-acceptor
assemblies: the effect of vibronic coupling.
AB - Thanks to major advances in laser technologies, recent investigations of the
ultrafast coupling of nuclear and electronic degrees of freedom (vibronic
coupling) have revealed that such coupling plays a crucial role in a wide range
of photoinduced reactions in condensed phase supramolecular systems. This paper
investigates several new donor-bridge-acceptor charge-transfer molecular
assemblies built on a trans-Pt(II) acetylide core. We also investigate how
targeted vibrational excitation with low-energy IR light post electronic
excitation can perturb vibronic coupling and affect the efficiency of electron
transfer (ET) in solution phase. We compare and contrast properties of a range of
donor-bridge-acceptor Pt(II) trans-acetylide assemblies, where IR excitation of
bridge vibrations during UV-initiated charge separation in some cases alters the
yields of light-induced product states. We show that branching to multiple
product states from a transition state with appropriate energetics is the most
rigid condition for the type of vibronic control we demonstrate in our study.
PMID- 26428718
TI - A Calaxin Gene in the Pacific Oyster Crassostrea gigasand Its Potential Roles in
Cilia.
AB - calaxin is a newly identified calcium sensor gene that modulates the movement of
flagella (and possibly cilia). It was first identified from the ascidian Ciona
intestinalis, and its orthologs have been observed in a wide range of animals and
choanoflagellates. However, no calaxin-ortholog in a Lophotrochozoa species has
been reported so far. This leaves open the question of whether the modulation of
ciliary motility by calaxin is conserved among animals. We report a calaxin gene
from the Pacific oyster Crassostrea gigas. This gene, termed cgi-calaxin,
possesses three conserved EF-hand motifs as its orthologs from chordates. A
phylogenetic analysis confirmed its orthology. Expression analysis revealed high
expression in typical ciliated tissues such as gill and hepatopancreas. The
spatiotemporal expression of the gene during early development was investigated
using whole mount in situ hybridization. The results revealed that cgi-calaxin
mRNA was aggregated in ciliated tissues of early larvae such as prototroch and
velum. Immunofluorescence experiment further certified the ciliary localization
of Cgi-Calaxin protein in D-veligers. We prepared the recombinant protein of cgi
calaxin and proved it had the capacity to bind to calcium. These results support
the conserved roles of cgi-calaxin as a calcium sensor in ciliated cells and
enrich the current knowledge on regulatory mechanisms of molluscan cilia.
Moreover, we found the gene to be expressed in poorly ciliated tissues, such as
adductor muscle, indicating possible roles in non-ciliated cells, which merits
further investigation.
PMID- 26428719
TI - Population Genetic Structure and Species Status of Asiatic Toads (Bufo
gargarizans) in Western China.
AB - We investigated the population genetic structure of Asiatic toads (Bufo
gargarizans) from the mountains of western China to determine their species
status, using genotypic data of ten microsatellite DNA loci and DNA sequences
from one mitochondrial gene. A total of 197 samples from eight sites were
examined, which cover a large range of elevations (559-3457 m), as well as all
three traditionally defined species (or subspecies). AMOVA did not reveal any
particularly large among-groups structure, whether the sites were grouped by
drainage, elevation, region, or species (subspecies). Individual assignment tests
placed all samples into two genetic clusters, which largely corresponded to their
geographic locations. An isolation-by-distance pattern was also detected when an
outlier population (site 3) was excluded. Furthermore, a mitochondrial gene tree
revealed deep divergence among haplotypes, sometimes within the same site. The
clade patterns were partially associated with geographic distribution but had no
resemblance to the traditional 2- or 3-species classification. Overall, these
toad populations harbor a large amount of genetic diversity and have very high
population differentiation, but taken together the evidence suggests that all
populations belong to a single species. Our results are consistent with most
previous molecular studies, and we recommend using Bufo gargarizans to represent
all Asiatic toad populations from western China without subspecies division.
PMID- 26428721
TI - Sexual Dimorphisms of Appendicular Musculoskeletal Morphology Related to Social
Display in Cuban Anolis Lizards.
AB - In Anolis lizards, sexual dimorphism has been reported in morphological and
ecological traits. Males show larger body size and longer limbs related to
territorial combat and courtship display with the dewlap. Although functional
anatomical traits are closely related to locomotor behaviors, differences between
sexes in musculoskeletal traits on limbs remain unclear. We explored the
relationships among sexual dimorphisms in musculoskeletal morphology, habitat,
and locomotor traits in Anolis lizards. Specifically, we examined appendicular
musculoskeletal morphology in three species of Cuban Anolis by measuring muscle
mass and lengths of moment arms. Through comparisons of crossing locomotion, we
found that the runner species possessed larger extensors in hindlimbs, which are
advantageous for running, whereas the masses of the humeral and femoral
retractors were larger in climber species, allowing these lizards to hold up
their bodies and occupy tree substrates. Comparisons between the sexes showed
different trends among the three species. Males of A. porcatus, which inhabit
narrow branches or leaves, had stronger elbow extensors that maintain the display
posture. In contrast, males of A. sagrei, which occupy broad surfaces, did not
show sexual differences that affected social display. Moreover, A. bartschi
indicated sexual differences despite the absence of dewlapping behavior. Our
findings suggest that both sexes show fundamentally similar relationships between
muscular morphology and locomotor habits to adapt arboreal or terrestrial
substrates, and yet sexual dimorphism in forelimb muscles may additionally
affected by male specific display with the dewlap.
PMID- 26428720
TI - An Anomalous Hatchery-Reared Biwa Rock Catfish, Silurus lithophilus (Teleostei:
Siluridae),with an Adipose Fin-Like Projection.
AB - An anomalous individual with an adipose fin-like projection was discovered during
seedling production of Biwa rock catfish, Silurus lithophilus (Teleostei:
Siluridae). The external shape of the projection resembled an adipose fin, but
soft rays were clearly observed within it. The projection was proximally
supported by a series of pterygiophores and by 14 soft rays. The projection can
be explained as: I, homologous with a primitive adipose fin, which occurred as a
result of localized ontogenetic reversion; II, an extra fin that occurred as a
result of abnormal expression of a regeneration mechanism; III, a remnant of a
dorsal fin and/or a second dorsal fin; and IV, an inversion phenomenon of the
polarity in the formation process of the anal fin.
PMID- 26428722
TI - Tolerance to Elevated Temperature and Ocean Acidification of the Larvae of the
Solitary Corals Fungia fungites (Linnaues, 1758) and Lithophyllon repanda (Dana,
1846).
AB - Increase in atmospheric CO2is the main driver of global climate change and is
projected to elevate sea surface temperature by at least 2 degrees C and to
decrease oceanic pH by 0.3 to 0.4 units by the end of the century. These factors
seriously threaten coral reef ecosystems worldwide. In Okinawa, solitary corals
are an important feature of the coral community structure. While previous studies
on the effects of ocean warming (OW), ocean acidification (OA) and its
combination on larval survival focused on colonial coral species, the present
study assessed the effect of high temperature on larvae from solitary corals. In
this study, we examined the influence of OW (control = 28 degrees C; control +3 =
31 degrees C; control + 6 = 34 degrees C) and OA (control, pCO2= 400 to 500
MUatm; medium, pCO2= 1000 to 1300 MUatm; high, pCO2= 1700 to 2200 MUatm) on the
larval survival of two solitary corals, Fungia fungites and Lithophyllon repanda
for eight days. Results showed that F. fungites was neither affected by OW, OA,
nor its combination. Similarly, survival of L. repanda was not affected by OA
however it was significantly affected by temperature. Temperature tolerance
varies between species; L. repanda (+3 degrees C above ambient) has lower
tolerance than F. fungites (+6 degrees C above ambient). This observation
suggests that fungiid larvae had higher tolerance to elevated temperature stress
relative to other scleractinian corals. With the projected increase in OW and OA
in the future, fungiidsmay retain good potential to widely disperse and
successfully recruit to natal and other neighbouring reefs.
PMID- 26428723
TI - Gonadal Morphology, Histology, and Endocrinological Characteristics of Immature
Female Whale Sharks, Rhincodon typus.
AB - Captive breeding of whale sharks is one of the great challenges for aquariums.
However, there is limited information available related to reproductive
physiology due to the difficulty of sampling and long-term observation. In the
present report, we provide information on the reproductive physiology of female
whale sharks, which were incidentally captured as bycatch in a set-net off the
coast of Okinawa, Japan. Total lengths of three captured female whale sharks were
403, 665, and 761 cm, respectively, at the time of their death. Collected paired
ovaries differed in size between right and left. However, it seems not to
determine which side of ovary becomes developed. Histological observations
revealed that oocytes surrounded by follicle cell layers localized in the
developed ovary, and most developed oocytes exhibited yolk vesicle stage.
Additionally, in the largest specimen, there were low levels of three steroid
hormones (Testosterone, Dihydrotestosterone, and Estradiol-17beta) that did not
show seasonal variation. The present results indicate that even the whale shark
over 7 m in TL are still histologically and endocrinologically immature. We
expect that the present data will provide fundamental information related to
reproductive physiology of female whale sharks, and will contribute to protection
activities and increased success in captive breeding of whale sharks.
PMID- 26428724
TI - Androgenic Gland Implantation Induces Partial Masculinization in Marmorkrebs
Procambarus fallax f. virginalis.
AB - The androgenic gland in malacostracan crustacean species produces and secretes
androgenic gland hormone, which is responsible for male sexual differentiation,
such as the induction and development of male sexual traits, and in turn the
suppression of female sexual traits. Marmorkrebs, Procambarus fallax forma
virginalis, which was identified as the first parthenogenetic species in decapod
crustaceans, produces only female offspring. In this study, in order to reveal
whether the Marmorkrebs crayfish is sensitive to androgenic gland hormone, we
transplanted an androgenic gland from a related congener, P. clarkii, to P.
fallax f. virginalis. In androgenic gland-implanted specimens, partial
masculinization was confirmed: the masculinization of several external sexual
characteristics (i.e., thickening of the first and second pleopods; formation of
reverse spines on the third and fourth pereopods) was detected, whereas that of
internal sexual characteristics (e.g., the formation of ovotestes and male
gonoducts) was not. Our results imply that P. fallaxf. virginalis still has
sensitivity to the androgenic gland hormone and, at least partly, the hormone
should be able to induce male characteristics, even in parthenogenetic
Marmorkrebs.
PMID- 26428725
TI - A Flatworm from the Genus Waminoa (Acoela: Convolutidae) Associated with Bleached
Corals in Western Australia.
AB - A flatworm isolated from bleached colonies of the coral Coscinaraea marshae at
Rottnest Island, Western Australia, is described using a combination of
morphological and molecular systematics. This flatworm shares morphological
features characteristic of the genus Waminoa (Acoelomorpha: Acoela), including
the presence of two algal symbionts, but appears to have genital regions
different from those of other described species of Waminoa. The design of new
oligonucleotide primers enabled the amplification of partial 18S rDNA of the
Rottnest Island acoel specimens, and phylogenetic analysis positioned them within
Waminoa, confirming their placement in the genus. Furthermore, Waminoa specimens
from Rottnest Island grouped into a sister clade to Waminoa brickneri, indicating
that the morphological and genetic differences observed are most likely
intraspecific and due to geographic variation. As such, we name these Rottnest
Island specimens W. cf. brickneri, but highlight that key differences warrant
further exploration before assignment to this species can be confirmed. This is
the first acoel flatworm described from Western Australia and contributes to our
understanding of the diversity and evolutionary relationship of the Acoela.
PMID- 26428726
TI - A New Species of Meristogenys (Anura: Ranidae) from Sarawak, Borneo.
AB - A cryptic Bornean torrent frog of the genus Meristogenys, which is divergent
genetically and morphologically from all known congeners, is described from
mountain streams of western Sarawak, East Malaysia (Borneo). The species occurs
sympatrically with the type species of the genus, M. jerboa, but apparently
differs from it in adult coloration and larval morphology, such as keratodont
formulae and glands in tail fins. Females of the new species possess much larger
and fewer eggs than in sympatric M. jerboa, suggesting significantly different
reproductive traits between these species. A key to larvae of known species of
the genus is provided.
PMID- 26428727
TI - Cribrilina mutabilis n. sp., an Eelgrass-Associated Bryozoan (Gymnolaemata:
Cheilostomata) with Large Variationin Zooid Morphology Related to Life History.
AB - We describe the cribrimorph cheilostome bryozoan Cribrilina mutabilis n. sp.,
which we detected as an epibiont on eelgrass (Zostera marina) at Akkeshi,
Hokkaido, northern Japan. This species shows three distinct zooid types during
summer: the R (rib), I (intermediate), and S (shield) types. Evidence indicates
that zooids commit to development as a given type, rather than transform from one
type to another with age. Differences in the frontal spinocyst among the types
appear to be mediated by a simple developmental mechanism, acceleration or
retardation in the production of lateral costal fusions as the costae elongate
during ontogeny. Colonies of all three types were identical, or nearly so, in
partial nucleotide sequences of the mitochondrial COI gene (555-631 bp),
suggesting that they represent a single species. Zooid types varied temporally in
overall frequency in the population: colonies contained nearly exclusively R-type
zooids in mid-June; predominantly I-type, or both R- and I-type, zooids in mid
July; and I-type, S-type, or both I- and S-type zooids (interspersed or in
discrete bands) in mid- to late August. Reproduction occurred throughout the
season, but peaked in July, with only R- and I-type zooids reproducing.
Reproductive zooids bear a vestigial compound (tripartite) ooecium and brood
internally; S-type zooids, first appearing in August, were non-reproductive,
which suggests that they may serve as an overwintering stage. As this species is
easily accessible, common, and simple in form, it is potentially useful as a
model system for studying polyphenism at multiple levels (zooid, colony, and
population) in the context of life-history adaptations.
PMID- 26428728
TI - Adalimumab for refractory pulmonary sarcoidosis.
AB - BACKGROUND: Ireland has one of the highest prevalence of sarcoidosis globally.
Currently anti-TNF treatment in sarcoidosis is considered on a case-by-case basis
particularly in patients who have a sub-optimal response to corticosteroid
therapy. AIMS: We report our experience of Adalimumab in a series of refractory
pulmonary sarcoidosis and discuss implications for treatment. CONCLUSION:
Symptomatic improvement was found in all patients as well as stabilisation or
improvement in DLCO sb. Improvements in pulmonary function tests correlated well
to radiological stage and length of disease.
PMID- 26428729
TI - In vitro and in silico comparative evaluation of anti-Acinetobacter baumannii
peptides.
AB - To control the infection caused by a multi-drug resistant bacterial pathogen,
Acinetobacter baumannii, antimicrobial peptides (AMPs) are being considered as a
viable option because of their broad range of antimicrobial activity and non
specific mode of action. However, high cost of synthesis of AMPs has led to the
development of several computational tools to predict the biological and
physicochemical properties of AMPs. In the present study, a comparative analysis
has been done between in vitro activity of seven anti-Acinetobacter alpha-helical
peptides with in silico prediction tools for studying antimicrobial related
properties of AMPs. Database of Antimicrobial Activity and Structure of Peptides
(DBAASP) and two algorithms, Support Vector Machine (SVM) and Random Forest (RF)
of another server, Collection of Antimicrobial Peptides (CAMP) were compared with
in vitro results of AMP/non-AMP nature of anti-Acinetobacter peptides. The
results of the influence of biophysical properties of peptides on their
antimicrobial activity suggested that amphipathicity is more important than
spatial arrangement and charge of alpha-helical peptides. No correlation was
observed between the MIC50 values and the hydropathy of AMPs. Based on the
present study, it is suggested that with further refinements in the available
servers/algorithms for correctly predicting the antimicrobial nature of the
peptides, in silico tools can be used to assist the development of new
antimicrobial agents.
PMID- 26428730
TI - Comparison of the Virulence-Associated Phenotypes of Five Species of
Acinetobacter baumannii Complex.
AB - In this study, we compared the virulence-associated factors of Acinetobacter
baumannii complex species. Sixty-three isolates of five A. baumannii complex
species, including 19 A. baumannii, 15 A. nosocomialis, 13 A. seifertii, 13 A.
pittii, and 3 A. calcoaceticus isolates, were included in this study. For all
isolates, biofilm formation, A549 cell adherence, resistance to normal human
serum, and motility were evaluated. A. baumannii complex isolates showed
diversity in biofilm formation, A549 cell adherence, and serum resistance, and no
strong positive relationships among these virulence characteristics. However, A.
seifertii showed relatively consistent virulence-associated phenotypes. In
addition, A. baumannii clone ST110 exhibited consistently high virulence
associated phenotypes. Motility was observed in seven isolates, and all four A.
baumannii ST110 isolates showed twitching motility. Although some inconsistencies
in virulence-associated phenotypes were seen, high virulence characteristics were
observed in A. seifertii, which has been mainly reported in Korea and shows high
rates of colistin resistance.
PMID- 26428731
TI - Cloning, Purification, and Characterization of a Heterodimeric beta-Galactosidase
from Lactobacillus kefiranofaciens ZW3.
AB - Lactobacillus kefiranofaciens ZW3 was obtained from kefir grains, which have high
lactose hydrolytic activity. In this study, a heterodimeric LacLM-type beta
galactosidase gene (lacLM) from ZW3 was isolated, which was composed of two
overlapping genes, lacL (1,884 bp) and lacM (960 bp) encoding large and small
subunits with calculated molecular masses of 73,620 and 35,682 Da, respectively.
LacLM, LacL, and LacM were expressed in Escherichia coli BL21(DE3) and these
recombinant proteins were purified and characterized. The results showed that,
compared with the recombinant holoenzyme, the recombinant large subunit exhibits
obviously lower thermostability and hydrolytic activity. Moreover, the optimal
temperature and pH of the holoenzyme and large subunit are 60 degrees C and 7.0,
and 50 degrees C and 8.0, respectively. However, the recombinant small subunit
alone has no activity. Interestingly, the activity and thermostability of the
large subunit were greatly improved after mixing it with the recombinant small
subunit. Therefore, the results suggest that the small subunit might play an
important role in maintaining the stability of the structure of the catalytic
center located in the large subunit.
PMID- 26428733
TI - Analysis of Bacterial Diversity and Communities Associated with Tricholoma
matsutake Fruiting Bodies by Barcoded Pyrosequencing in Sichuan Province,
Southwest China.
AB - Endophytes play an important role in the growth and development of the host.
However, the study of endophytes is mostly focused on plants, and reports on
bacteria associated with fungi are relatively rare. We studied the bacteria
associated with fruiting bodies of Tricholoma matsutake picked from seven main T.
matsutake-producing areas in Sichuan, China, by barcoded pyrosequencing. About
8,272 reads were obtained per sample, representing 40 phyla, 103 classes, and 495
genera of bacteria and archaea, and 361-797 operational taxonomic units were
observed at a 97% similarity level. The bacterial community was always both more
abundant and more diverse than the archaeal community. UniFrac analysis showed
there were some difference of bacterial communities among the samples sites.
Three bacterial phyla, Proteobacteria, Bacteroidetes, and Firmicutes, were
dominant in all samples. Correlation analysis showed there was a significant
correlation between some soil properties and bacterial community associated with
T. matsutake. This study demonstrated that the bacteria associated with T.
matsutake fruiting bodies were diversified. Among these bacteria, we may find
some strains that can promote the growth of T. matsutake.
PMID- 26428734
TI - Clinical Evidence of Effects of Lactobacillus plantarum HY7714 on Skin Aging: A
Randomized, Double Blind, Placebo-Controlled Study.
AB - The beneficial effects of probiotics are now widely reported, although there are
only a few studies on their anti-aging effects. We have found that Lactobacillus
plantarum HY7714 (HY7714) improves skin hydration and has anti-photoaging
effects, and in the present study, we have further evaluated the anti-aging
effect of HY7714 via a randomized, double blind, placebo-controlled clinical
trial. The trial included 110 volunteers aged 41 and 59 years who have dry skin
and wrinkles. Participants took 1 * 10(10) CFU/day of HY7714 (probiotic group) or
a placebo (placebo group) for 12 weeks. Skin hydration, wrinkles, skin gloss, and
skin elasticity were measured every 4 weeks during the study period. There were
significant increases in the skin water content in the face (p < 0.01) and hands
(p < 0.05) at week 12 in the probiotic group. Transepidermal water loss decreased
significantly in both groups at weeks 4, 8, and 12 (p < 0.001 compared with
baseline), and was suppressed to a greater extent in the face and forearm in the
probiotic group at week 12. Volunteers in the probiotic group had a significant
reduction in wrinkle depth at week 12, and skin gloss was also significantly
improved by week 12. Finally, skin elasticity in the probiotic group improved by
13.17% (p < 0.05 vs. controls) after 4 weeks and by 21.73% (p < 0.01 vs.
controls) after 12 weeks. These findings are preliminary confirmation of the anti
aging benefit to the skin of L. plantarum HY7714 as a nutricosmetic agent.
PMID- 26428735
TI - Tracking Study About Adenovirus 36 Infection: Increase of Adiposity.
AB - This study investigated the cross-sectional and longitudinal association between
adenovirus 36 (Ad36) and obesity in 79 Korean adolescent boys over 1 year. We
analyzed the changes in body composition and metabolic risk factors according to
the presence of Ad36 antibodies. Ad36 antibodies in serum were detected using the
constant virus-decreasing serum method. We found that the fat percentage and
fasting insulin in the Ad36-seropositive group were greater than the Ad36
seronegative group. These results suggest that Ad36 infection is associated with
an increase of adiposity, and the experience of Ad36 infection may affect the
future fat gain of adolescents.
PMID- 26428736
TI - [Organization of collaborative deliberation for limiting or withholding
treatments in children].
AB - In 2005, the French law on patients' rights at the end of life required that
decisions to withdraw or withhold life-sustaining treatments be made and carried
out by the physician in charge of the patient, after obtaining advice from an
independent consulting colleague and the caregiving team. The purpose of this
study was to identify theoretical and practical obstacles to this collaborative
deliberation and to propose practical guidelines to organize it.
PMID- 26428737
TI - [Exocrine pancreatic insufficiency and Turner syndrome: a pediatric case report].
PMID- 26428732
TI - Cell-Based Assay Design for High-Content Screening of Drug Candidates.
AB - To reduce attrition in drug development, it is crucial to consider the
development and implementation of translational phenotypic assays as well as
decipher diverse molecular mechanisms of action for new molecular entities. High
throughput fluorescence and confocal microscopes with advanced analysis software
have simplified the simultaneous identification and quantification of various
cellular processes through what is now referred to as highcontent screening
(HCS). HCS permits automated identification of modifiers of accessible and
biologically relevant targets and can thus be used to detect gene interactions or
identify toxic pathways of drug candidates to improve drug discovery and
development processes. In this review, we summarize several HCS-compatible,
biochemical, and molecular biology-driven assays, including immunohistochemistry,
RNAi, reporter gene assay, CRISPR-Cas9 system, and protein-protein interactions
to assess a variety of cellular processes, including proliferation, morphological
changes, protein expression, localization, post-translational modifications, and
protein-protein interactions. These cell-based assay methods can be applied to
not only 2D cell culture but also 3D cell culture systems in a high-throughput
manner.
PMID- 26428738
TI - Methylene blue treatment for resistant shock following renal transplantation.
AB - We report a case of a 19-year-old female with a history of hyperoxaluria type 1
and renal failure. The patient presented for a second renal transplantation 17
years after her first combined liver and kidney transplantation. Postoperative
shock was highly resistant to fluids and required massive pharmacologic
hemodynamic support. Vasoplegic shock was the presumed diagnosis, and methylene
blue was utilized as a rescue therapy, with a rapid hemodynamic response and no
apparent side effects.
PMID- 26428739
TI - Experimental manipulation of floral scent bouquets restructures flower-visitor
interactions in the field.
AB - A common structural feature of natural communities is the non-random distribution
of pairwise interactions between organisms of different trophic levels. For plant
animal interactions, it is predicted that both stochastic processes and
functional plant traits that facilitate or prevent interactions are responsible
for these patterns. However, unbiased manipulative field experiments that
rigorously test the effects of individual traits on community structure are
lacking. We address this gap by manipulating floral scent bouquets in the field.
Manipulation of floral scent bouquets led to quantitative as well as qualitative
restructuring of flower-visitor networks, making them more generalized.
Olfactometer trials confirmed both positive and negative responses to scent
bouquets. Our results clearly show that the distribution of insect visitors to
the two abundant study plant species reflects the insects' species-specific
preferences for floral scents, rather than for visual or morphological floral
traits. Thus, floral scents may be of major importance in partitioning flower
visitor interactions. Integrating experimental manipulations of plant traits with
field observations of interaction patterns thus represents a promising approach
for revealing the processes that structure species assemblages in natural
communities.
PMID- 26428740
TI - Angiopoietin-2 is a negative prognostic marker in small cell lung cancer.
AB - BACKGROUND: Small cell lung cancer (SCLC) is a highly lethal disease due to its
chemorefractory nature after initial treatment. Angiogenesis plays an important
role in tumor growth, metastasis and chemoresistance. We hypothesized that
angiogenesis could predict chemoresistance in SCLC patients and be potentially a
therapeutic target in this disease. METHODS: Serum samples from forty-three SCLC
patients were prospectively obtained at diagnosis, response evaluation and
progression. Angiogenesis-related cytokines (Angiopoietin-2, VEGF-A, C and D)
were simultaneously quantified by Luminex Technology. Clinical data were
prospectively recorder. RESULTS: Significantly higher concentration of
angiogenesis-related cytokines were found in SCLC patients at diagnosis compared
to healthy volunteers. High baseline serum concentration of Angiopoietin-2
(sAngiopoietin-2) were associated with a worse overall survival (p=0.006) and
remained independently associated with survival in the multivariate analysis
(p=0.008). In addition, sAngiopoietin-2 significantly increased at progression
when compared to baseline. CONCLUSION: These data provide novel evidence on a
role of sAngiopoietin-2 in the adverse clinical behavior of SCLC and could be a
potential therapeutic target in this disease.
PMID- 26428741
TI - The bronchiolitis season is upon us--recommendations for the management and
prevention of acute viral bronchiolitis.
AB - Despite being so common, bronchiolitis remains poorly diagnosed and managed. This
article is intended as an update on issues pertaining to this condition.
PMID- 26428742
TI - Doctor-assisted suicide: What is the present legal position in South Africa?
AB - In the recent case of Stransham-Ford v. the Minister of Justice and Correctional
Services, the North Gauteng High Court held that a terminally ill patient who was
experiencing intractable suffering was entitled to commit suicide with the
assistance of his doctor and that the doctor's conduct would not be unlawful. The
court was careful to state that it was not making a general rule about doctor
assisted suicide. The latter should be left to the Parliament, the Constitutional
Court and 'future courts'. The judge dealt specifically with the facts of the
case at hand. In order to understand the basis of the decision it is necessary to
consider: (i) the facts of the case; (ii) the question of causation; (iii) the
paradox of 'passive' and 'active' euthanasia; (iv) the test for unlawfulness in
euthanasia cases; and (v) the meaning of doctor-assisted suicide. It is also
necessary to clarify the present legal position regarding doctor-assisted
suicide.
PMID- 26428743
TI - The importance of identified cause-of-death information being available for
public health surveillance, actions and research.
AB - An amendment to the South African Births and Deaths Registration Act has
compromised efforts to strengthen local mortality surveillance to provide
statistics for small areas and enable data linkage to provide information for
public health actions. Internationally it has been recognised that a careful
balance needs to be kept between protecting individual patient confidentiality
and enabling effective public health intelligence to guide patient care and
service delivery and prevent harmful exposures. This article describes the public
health benefits of a local mortality surveillance system in the Western Cape
Province, South Africa (SA), as well as its potential for improving the quality
of vital statistics data with integration into the national civil registration
and vital statistics system. It also identifies other important uses for
identifiable cause-of-death data in SA that have been compromised by this
legislation.
PMID- 26428744
TI - Social franchising primary healthcare clinics--a model for South African National
Health Insurance?
AB - This article describes the first government social franchise initiative in the
world to deliver a 'brand' of quality primary healthcare (PHC) clinic services.
Quality and standards of care are not uniformly and reliably delivered across
government PHC clinics in North West Province, South Africa, despite government
support, numerous policies, guidelines and in-service training sessions provided
to staff. Currently the strongest predictor of good-quality service is the skill
and dedication of the facility manager. A project utilising the social
franchising business model, harvesting best practices, has been implemented with
the aim of developing a system to ensure reliably excellent healthcare service
provision in every facility in North West. The services of social franchising
consultants have been procured to develop the business model to drive this
initiative. Best practices have been benchmarked, and policies, guidelines and
clinic support systems have been reviewed, evaluated and assessed, and
incorporated into the business plan. A pilot clinic has been selected to refine
and develop a working social franchise model. This will then be replicated in one
clinic to confirm proof of concept before further scale-up. The social franchise
business model can provide solutions to a reliable and recognisable 'brand' of
quality universal coverage of healthcare services.
PMID- 26428745
TI - The state of South African internships: A national survey against HPCSA
guidelines.
AB - BACKGROUND: Medical internship is designed to bridge the gap between the
theoretical knowledge learned as a student and the skills required as a competent
medical practitioner. In South Africa (SA) it is a 2-year structured programme
incorporating experience in key domains of medicine selected by the Health
Professions Council of South Africa (HPCSA). HPCSA guidelines state that the
clinical experience should include teaching, supervision and competency in
selected logbook procedures. After concerns were raised over some accredited
intern facilities, we investigated whether these guidelines were being met for
interns across SA. METHODS: An electronic survey was sent to 150 SA doctors who
had completed their internship between 2010 and 2013. The questions covered
supervision, workload and rest, teaching and perception of patient safety. All
responses were anonymous and there was opportunity to comment at the end of each
question. RESULTS: The respondents (n=90) included graduates from all eight SA
medical schools. Supervision was ranked as the aspect of internship that
respondents would change the most, with 33.0% performing an interventional
procedure for the first time without supervision and 25.6% experiencing an
adverse event where senior help was not available. More than half the interns had
an entire shift supervised by a medical officer with less than 3 years' clinical
training in that specialty. CONCLUSIONS: This survey identified deficiencies of
supervision as directed by the HPCSA. It also highlighted difficulties with
workload and teaching opportunities. A significant proportion of interns did not
feel that patients were safe under their care. A national annual HPCSA survey
would highlight hospitals where closer investigation may be required.
PMID- 26428746
TI - A South African family with oculopharyngeal muscular dystrophy: Clinical and
molecular genetic characteristics.
AB - Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is
caused by a trinucleotide repeat expansion in exon 1 of the polyadenylate binding
protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was
recently identified in Pretoria, South Africa (SA). Molecular studies revealed a
(GCG)11(GCA)3GCG or (GCN)15 mutant allele. The (GCN)15 mutation detected in this
family has been described previously in families from Uruguay and Mexico as a
founder effect. To our knowledge, this is the first report of an SA Afrikaner
family with molecularly confirmed OPMD. The proband, a 64-year-old woman,
presented to the neurology outpatient department at Steve Biko Academic Hospital,
Pretoria. A sibship of 18 individuals was identified, of whom eight had OPMD.
Four patients were interviewed and examined clinically, and electromyographic
studies were performed. Molecular analysis of the PABPN1 gene was performed by
polymerase chain reaction amplification and direct sequencing of exon 1 in three
of the patients. Patients presented with ptosis, external ophthalmoplegia,
dysphagia, dysarthria and mild proximal weakness. High foot arches and absent
ankle reflexes raised the possibility of peripheral neuropathy, but
electromyography showed only mildly low sensory amplitudes, and myopathic units
in two patients.
PMID- 26428747
TI - Understanding the genetic diversity of South Africa's peoples.
PMID- 26428748
TI - Genomics in medicine: From promise to practice.
PMID- 26428749
TI - Impact of fibrinolytics on the outcome of empyema in South African children.
AB - BACKGROUND: Childhood pneumonia is common in all countries, and empyema is one of
the commonest complications. The role of routine intrapleural fibrinolytics in
the management of childhood empyema is not well established in low- and middle
income countries. METHODS: We did a prospective observational study of children
sequentially hospitalised with empyema between December 2006 and December 2011 in
South Africa (SA). Intrapleural tissue plasminogen activator (TPA), administered
according to a standard protocol, was introduced in September 2009. Outcomes in
children treated with TPA after 2009 were compared with the historical cohort not
treated with TPA who met the treatment criteria. RESULTS: One hundred and forty
two children with empyema, median age 17 months (interquartile range 8-43), were
admitted during the study period. Excluding children who did not have a chest
tube inserted and those in whom fibrinolysis was contraindicated, there were 99
patients, 52 of whom received fibrinolytics. Clinical characteristics and empyema
aetiology were similar in those who received fibrinolysis and those who did not.
Eighteen children (38.3%) not treated with TPA required surgery v. 5 (9.6%)
treated with TPA (relative risk 0.25; 95% confidence interval 0.1-0.6). The
median duration of hospitalisation was similar in both groups. Complications
occurred rarely and with a similar incidence in both groups. In-hospital
mortality was low, with two deaths in each group. CONCLUSION: Intrapleural TPA
resulted in a four-fold reduction in surgery. Fibrinolytics should be used for
management of empyema in children in SA.
PMID- 26428750
TI - The impact of highly active antiretroviral therapy on the burden of bacterial
lower respiratory tract infections in children.
AB - BACKGROUND: Respiratory diseases are common and associated with significant
morbidity and mortality in children. OBJECTIVE: To evaluate the prevalence and
outcome of bacterial lower respiratory tract infections (LRTIs) in HIV-infected
and uninfected children at a primary level hospital. METHODS: A cross-sectional
descriptive study of children aged 6 months-18 years was conducted. Recruitment
included HIV-positive children who had been on highly active antiretroviral
therapy (HAART) for at least 6 months. A comparator group of HIV-negative
children admitted with bacterial pneumonia was included. Laboratory data
collected included CD4+ T-cell counts, HIV viral load and C-reactive protein
(CRP). Data collected in both groups included demographic data, immunisation
status, zinc supplementation, previous LRTIs, environmental exposures and
treatment. RESULTS: Fifty-nine HIV-infected and 20 uninfected children were
enrolled. The HIV-positive children were older, with a mean age of 107.2
(standard deviation 50.0) months v. 12.0 (5.8) months (p<0.005). The HIV-infected
group had a mean CD4 percentage of 31.5%, and had had an average of 3.9 visits
for bacterial LRTIs. All were treated with amoxicillin with no complications. In
the HIV-uninfected group, cough and rapid breathing were the most common
presenting symptoms, and the mean CRP level was 463.0 mg/L. The mean hospital
stay was 4 days. CONCLUSION: HAART is effective in reducing the burden of LRTIs
in HIV-positive children, even when the diagnosis is delayed. Cough and fast
breathing are still the most reliable presenting symptoms of pneumonia. The
majority of children still respond to amoxicillin as first-line therapy, with low
complication rates.
PMID- 26428751
TI - Identification of a mutation in the ubiquitin-fold modifier 1-specific peptidase
2 gene, UFSP2, in an extended South African family with Beukes hip dysplasia.
AB - BACKGROUND: Beukes hip dysplasia (BHD) is an autosomal dominant disorder of
variable penetrance that was originally identified in a large South African
family of European origin. BHD is characterised by bilateral dysmorphism of the
proximal femur, which results in severe degenerative osteoarthropathy. Previous
studies mapped the disorder to a 3.34 Mb region on chromosome 4q35. OBJECTIVE: To
fine-map the BHD locus and identify the disease-causing mutation by direct
sequencing. RESULTS: The linked BHD allele was refined to 1.33 Mb, reducing the
number of candidate genes from 25 to 16. Analysis of protein coding and invariant
splice-site sequences in three distantly related individuals identified a single
candidate disease-causing variant c.868T>C within exon 8 of the ubiquitin-fold
modifier 1 (Ufm1)-specific peptidase 2 gene, UFSP2. The presence of this unique
mutation was confirmed in all 17 affected members of the BHD family who were
genotyped. The mutation segregated with the BHD phenotype in the extended family
with a two-point (single marker) LOD score of 10.4 (theta=0.0 and 80%
penetrance). The mutation predicts the substitution of a highly conserved amino
acid, p.Tyr290His, in the encoded protein. In vitro functional assays performed
using purified recombinant wild-type and mutant UFSP2 protein demonstrated that
the BHD mutation abolishes UFSP2-mediated C-terminal cleavage of its substrate,
Ufm1. CONCLUSION: We report a unique UFSP2 mutation that segregates with the BHD
phenotype. The predicted amino acid substitution inactivates UFSP2 proteolytic
function, thus implicating the ubiquitin-fold modifier 1 cascade in this form of
severe hip osteoarthropathy. The facile polymerase chain reaction-based assay we
describe could be used to confirm the diagnosis of BHD, or for presymptomatic
testing of members of the extended BHD family.
PMID- 26428753
TI - Prevalence of Blomia tropicalis allergy in two regions of South Africa.
AB - BACKGROUND: Asthma and allergic rhinitis affect 15% and 38% of South African (SA)
children, respectively. The housedust mite (HDM) is the most significant indoor
aeroallergen. Typical HDM species include Dermatophagoides pteronyssinus, D.
farinae and Blomia tropicalis. Conventional skin-prick testing (SPT) panels only
test for Dermatophagoides. B. tropicalis has been described in the tropical and
subtropical regions, but is not routinely tested for in SA. OBJECTIVE: To
ascertain the significance of B. tropicalis as an aeroallergen in northern
coastal KwaZulu-Natal Province (KZN), a tropical environment, and in Johannesburg
in the highveld, where the climate is milder and less humid. METHODS: Children
aged 1-18 years with features of allergic rhinitis and/or asthma were recruited
over a 6-month period from Alberlito Hospital in northern KZN and the Clinton
Clinic in Johannesburg. SPTs included Dermatophagoides and B. tropicalis.
Sensitisation was defined as a wheal 3 mm greater than the negative control.
RESULTS: Eighty-five subjects were included, 50 in northern KZN and 35 in the
Johannesburg arm; 52% of subjects in northern KZN and 3% in Johannesburg were
sensitised to B. tropicalis, with a significant difference between these centres
(p<0.05). Of the 52% sensitised to B. tropicalis in northern KZN, half were
sensitised only to B. tropicalis. CONCLUSION: There is a high prevalence of B.
tropicalis allergy in the tropical northern KZN region and a much lower
prevalence in the Johannesburg region. Routine testing for B. tropicalis allergy
should be employed in northern KZN.
PMID- 26428752
TI - Impact of an educational intervention and clinical performance dashboard on
neonatal bloodstream infections.
AB - BACKGROUND: Blood cultures are the most direct method of detecting bacteraemia.
Reducing contamination rates improves the specificity and positive predictive
value of the blood culture. Clinical performance dashboards have been shown to be
powerful tools in improving patient care and outcomes. OBJECTIVES: To determine
whether prospective surveillance of bloodstream infections (BSIs), introduction
of an educational intervention and the use of a clinical performance dashboard
could reduce BSIs and blood culture contamination rates in a neonatal nursery.
METHODS: We compared two time periods, before and after an intervention. Blood
culture data were extracted from the local microbiology laboratory database. The
educational intervention included the establishment of hand-washing protocols,
blood culture techniques and video tools. A clinical performance dashboard was
developed to demonstrate the monthly positive blood culture and contamination
rates, and this was highlighted and referred to weekly at the unit staff meeting.
RESULTS: Before the intervention, 1 460 blood cultures were taken; 206 (14.1%)
were positive, of which 104 (7.1% of the total) were contaminants. In the period
following the intervention, 1 282 blood cultures were taken; 131 (10.2%) were
positive, of which 42 (3.3% of the total) were contaminants. The number of
positive blood cultures and contamination rates after the intervention were both
statistically significantly reduced (p=0.002 and p<0.001, respectively).
CONCLUSION: This study demonstrates that adopting a relatively simple educational
tool, making use of a clinical performance dashboard indicator and benchmarking
practice can significantly reduce the level of neonatal sepsis while also
reducing contaminated blood cultures.
PMID- 26428754
TI - Nodular thyroid disease and thyroid malignancy: Experience at Polokwane Mankweng
Hospital Complex, Limpopo Province, South Africa.
AB - BACKGROUND: Nodular thyroid disease is common throughout the world. Numbers of
patients with goitre are increasing worldwide, as also noted in Limpopo Province,
South Africa (SA). Globally, thyroid nodules have been reported in 4-7% of the
population on neck palpation and in 30-50% by ultrasonography. OBJECTIVES: To
review the profile of thyroid disease in patients with goitre presenting to the
Department of Surgery at Polokwane Mankweng Hospital Complex (PMHC), Limpopo, SA,
to characterise the pattern of malignancy in patients with goitre, and to
determine the most common thyroid cancer. METHOD: A 6-year retrospective study
(2003-2008) of all patients with thyroid nodules who underwent thyroid surgery at
PMHC. RESULTS: The study group included 90 patients (mean age 45 years, range 4
80). The male-to-female ratio was 1:17 (5 men, 85 women). Of these patients, 80
(89.9%) had benign lesions, of which 52 (57.8% of the total) were adenomas, 25
(27.8%) multinodular goitres (MNGs), 2 (2.2%) hyperplastic nodules and 1 (1.1%)
Hashimoto's thyroiditis. Ten patients (11.1%) had malignant lesions (7 follicular
carcinomas and 3 papillary carcinomas), of which 2 were found in MNGs.
CONCLUSIONS: Adenoma and MNG were the predominant non-malignant conditions
(85.6%). The prevalence of thyroid cancer in our study was 11.1%, and of all 90
patients, 7.8% had follicular carcinoma. The risk of malignancy in MNG was 8.9%.
Rates of thyroid nodules and carcinoma were highest in women aged 41-60 years. We
advocate that total thyroidectomy be considered for MNG, because MNG can harbour
incidental carcinoma.
PMID- 26428755
TI - Household fuel use and child respiratory ill health in two towns in Mpumalanga,
South Africa.
AB - BACKGROUND: This cross-sectional study examined respiratory health outcomes and
associated risk factors in children living in a part of South Africa
characterised by high levels of air pollution. METHODS: A questionnaire was used
to collect self-reported respiratory health and risk factor data from the
parents/guardians of children between the ages of 9 and 11 years attending
primary schools in the study area. Six government schools were selected based on
their location, class size and willingness to participate. Univariate and
bivariate analyses as well as logistic regression analysis were performed on the
data, using a p-value of 0.25 and biological plausibility. RESULTS: The overall
prevalence of respiratory ill-health symptoms was 34.1%. The prevalence of
respiratory ill-health conditions was significantly elevated among children from
households using non-electrical fuels v. electricity for cooking (43.9% v. 31.6%;
adjusted p-value 0.005). The same was noted among those using non-electrical
fuels for heating (37.8% v. 29.0%). CONCLUSION: The elevated prevalence of some
respiratory health outcomes among schoolchildren, especially in conjunction with
domestic fossil fuel burning, is of concern. The data collected in this study may
be used to complement or form a basis for future policy regarding indoor or
ambient air quality in the area.
PMID- 26428756
TI - Maternal near miss and maternal death in the Pretoria Academic Complex, South
Africa: A population-based study.
AB - BACKGROUND: In order to reduce maternal mortality in South Africa (SA), it is
important to understand the process of obstetric care, identify weaknesses within
the system, and implement interventions for improving care. OBJECTIVE: To
determine the spectrum of maternal morbidity and mortality in the Pretoria
Academic Complex (PAC), SA. METHODS: A descriptive population-based study that
included all women delivering in the PAC. The World Health Organization
definition, criteria and indicators of near miss and maternal death were used to
identify women with severe complications in pregnancy. RESULTS: Between 1 August
2013 and 31 July 2014, there were 26,614 deliveries in the PAC. The institutional
maternal mortality ratio was 71.4/100,000 live births. The HIV infection rate was
19.9%, and 2.7% of women had unknown HIV status. Of the women, 1120 (4.2%)
developed potentially life-threatening conditions and 136 (0.5%) life-threatening
conditions. The mortality index was 14.0% overall, 30.0% for non-pregnancy
related infections, 2.0% for obstetric haemorrhage and 13.6% for hypertension. Of
the women with life-threatening conditions, 39.3% were referred from the primary
level of care. Vascular, uterine and coagulation dysfunctions were the most
frequent organ dysfunctions in women with life-threatening conditions. The
perinatal mortality rate was 26.9/1000 births overall, 23.1/1000 for women with
non-life-threatening conditions, and 198.0/1000 for women with life-threatening
conditions. CONCLUSION: About one in 20 pregnant women in the PAC had a
potentially life-threatening condition; 39.3% of women presented to a primary
level facility as an acute emergency and had to be transferred for tertiary care.
All healthcare professionals involved in maternity care must have knowledge and
skills that equip them to manage obstetric emergencies. Review of the basic
antenatal care protocol may be necessary.
PMID- 26428757
TI - Intracranial suppuration: Review of an 8-year experience at Umtata General
Hospital and Nelson Mandela Academic Hospital, Eastern Cape, South Africa.
AB - BACKGROUND: Intracranial suppuration (ICS) is a life-threatening condition caused
by various disease processes and consisting of brain abscess and extradural and
subdural empyema. The major causes have changed over the decades. To the author's
knowledge, the incidence of ICS in South Africa (SA) has not been established.
OBJECTIVE: To determine the incidence of ICS, overall and according to age and
gender, and to identify the source and distribution of ICS. METHOD: The archive
of the radiology departments at Umtata General Hospital and Nelson Mandela
Academic Hospital in the Transkei region, Eastern Cape Province, SA, was searched
retrospectively for computed tomography (CT) reports of patients diagnosed with
ICS. Cases in which the CT images, patients' clinical information and CT reports
were available for an uninterrupted period of at least 1 year were included.
RESULTS: Five time frames were established, encompassing 8 years of data. The
first time frame established an incidence of ICS of 1/100,000/year for the
Transkei region. All the time frames were utilised to determine the incidence
according to gender and age, and the source and distribution of ICS. The
incidence of ICS was higher among males than females, and highest in the age
groups 0-10 and 11-20 years. A seasonal variation in the incidence of sinusitis-
and meningitis-related ICS was noted. Numbers of cases declined during the last 3
years of the study period. CONCLUSION: Sinusitis, head trauma, ear infection and
meningitis were the major sources of ICS. A pulmonary source was not a major
feature. In the last 4 years, trauma became the commonest source of ICS. A steady
decline in ear infection- and meningitis-related ICS was noted.
PMID- 26428759
TI - Evaluation of the diagnostic accuracy of the HemoCue device for detecting anaemia
in healthy school-aged children in KwaZulu-Natal, South Africa.
AB - BACKGROUND: The prevalence of anaemia in school-aged children is reported to be
high (>10%), yet neither the onset of anaemia nor the disease causing it is
easily established. Any form of anaemia, even if mild, can compromise children's
health and survival. This study was conducted to generate data to support or
reject use of the HemoCue device as a potential point-of-care method for
haemoglobin (Hb) assessment in field and primary healthcare settings. OBJECTIVE:
To assess the validity of the HemoCue in relation to the gold-standard laboratory
method. METHODS: A cross-sectional study of children aged 6-8 years, analysing
the diagnostic accuracy of the HemoCue in determining Hb levels in venous blood.
Agreement between the HemoCue and laboratory techniques was evaluated using the
Bland-Altman plot. The intra-class correlation coefficient was used to assess
within-subject variability of measured Hb. RESULTS: A trend of underestimation of
Hb values was noted. The mean Hb with the HemoCue was 11.70 g/dL and that with
the laboratory method 12.19 g/dL. The mean difference between the two methods was
0.49 g/dL, with a standard deviation of 0.77 g/dL (95% confidence interval -0.59-
0.38). Discrepancies>1 g/dL were identified in 14.1% of cases. Bias increased
with increasing Hb values. CONCLUSION: The HemoCue was found to be comparable to
the standard laboratory method for determining Hb concentrations in school-aged
children. Its usefulness for screening healthy children was demonstrated,
although a full blood count is recommended if anaemia or iron deficiency is
suspected.
PMID- 26428758
TI - Observed full blood count and lymphocyte subset values in a cohort of clinically
healthy South African children from a semi-informal settlement in Cape Town.
AB - BACKGROUND: The paediatric full blood count and lymphocyte subset reference
intervals used by the National Health Laboratory Service (NHLS), South Africa
(SA), are taken from two international reference interval publications.
Differences in reference intervals suggest that international data sets may not
be appropriate for use in SA. OBJECTIVE: To study immunohaematological values of
a group of clinically healthy children from an informal settlement in Cape Town,
SA, to assess whether international paediatric reference intervals used by the
NHLS are appropriate. METHODS: A cross-sectional study of 207 female and 174 male
HIV-uninfected children living in an informal settlement in Cape Town was
performed. Full blood counts, automated differential counts and lymphocyte subset
analysis were done using internationally accepted technologies. Data were
categorised by age and reference intervals compiled using medians and 95%
confidence intervals (CIs). Gender comparisons were calculated by non-parametric
tests. RESULTS: Although median and 95% CI values differed slightly,
physiological trends for red cell, platelet, white blood cell differential and
lymphocyte subsets were similar to international reference intervals currently in
use at the NHLS. Benign ethnic neutropenia was not a significant finding, and
gender-specific intervals were not necessary until 12 years of age. Lower overall
median values for haemoglobin and haematocrit, and higher median values for mean
cell volume and red cell distribution width, were noted. Assessment of
haemoglobin, red cell distribution width and calculated Mentzer ratios suggested
underlying iron deficiency in 14.2% of participants. CONCLUSION: Paediatric
immunohaematological reference intervals observed in this study are similar to,
and support continued use of, international paediatric reference intervals.
Underlying iron and related nutritional deficiencies may be contributing to lower
haemoglobin levels noted in local children. A larger nationwide study, including
all ethnic groups, is recommended.
PMID- 26428760
TI - Use of EMLA cream as a topical anaesthetic before venepuncture procedures in
field surveys: A practice that helps children, parents and health professionals.
AB - BACKGROUND: Topical analgesia is becoming essential as the number of invasive
screening procedures involving children rises steadily. Little is known about the
frequency of these procedures, or about interventions to ease the pain. METHODS:
We investigated the use of EMLA cream in 184 school-aged children in KwaZulu
Natal Province, South Africa. Another group of 20 children did not receive any
local analgesia and was assessed as a control. Anticipatory anxiety, pain,
adverse reactions and ease of procedure were assessed using a subjective visual
analogue scale (VAS) pain score generated by the researcher and obtained from
each child immediately after the procedure. RESULTS: The use of EMLA cream
resulted in reduced pain and distress. The pain-relieving influence of EMLA was
good (91.3% analgesic effect). Participants who received EMLA cream reported
significantly lower VAS pain scores (p=0.001). Pain scores generated by the
researcher were also significantly lower in the EMLA group than in the control
group (p=0.000). No adverse reactions were observed, and the children could
continue with other research activities during the application time and after the
procedure. Parent or caregiver scores were in favour of EMLA cream. CONCLUSION:
EMLA cream was safe and effective for alleviating the pain associated with
venepuncture in a fieldwork setting. We therefore believe that it merits a place
in the routine premedication of children before phlebotomy and cannulation
procedures in clinical settings, research studies and field surveys. Further
research is recommended to assess whether EMLA cream can be used for
immunisations.
PMID- 26428761
TI - The Cochrane Corner in the SAMJ: Summaries of Cochrane systematic reviews for
evidence-informed practice.
PMID- 26428762
TI - Anger and Afrophobia in South Africa: What is a health practitioner to do?
PMID- 26428763
TI - Modeling of thermoacoustic systems using the nonlinear frequency domain method.
AB - When modeling thermoacoustic (TA) devices at high amplitude, nonlinear effects
such as time-average mass flows, and the generation of higher harmonics can no
longer be neglected. Thus far, modeling these effects in TA devices required a
generally computationally costly time integration of the nonlinear governing
equations. In this paper, a fast one-dimensional nonlinear model for TA devices
is presented, which omits this costly time integration by directly solving the
periodic steady state. The model is defined in the frequency domain, which eases
the implementation of phase delays due to viscous resistance and thermoacoustic
heat exchange. As a demonstration, the model is used to solve an experimental
standing wave thermoacoustic engine. The obtained results agree with experimental
results, as well as with results from a nonlinear time domain model from the
literature. The low computational cost of this model opens the possibility to do
optimization studies using a nonlinear TA model.
PMID- 26428764
TI - Sources of variability in consonant perception of normal-hearing listeners.
AB - Responses obtained in consonant perception experiments typically show a large
variability across stimuli of the same phonetic identity. The present study
investigated the influence of different potential sources of this response
variability. It was distinguished between source-induced variability, referring
to perceptual differences caused by acoustical differences in the speech tokens
and/or the masking noise tokens, and receiver-related variability, referring to
perceptual differences caused by within- and across-listener uncertainty.
Consonant-vowel combinations consisting of 15 consonants followed by the vowel
/i/ were spoken by two talkers and presented to eight normal-hearing listeners
both in quiet and in white noise at six different signal-to-noise ratios. The
obtained responses were analyzed with respect to the different sources of
variability using a measure of the perceptual distance between responses. The
speech-induced variability across and within talkers and the across-listener
variability were substantial and of similar magnitude. The noise-induced
variability, obtained with time-shifted realizations of the same random process,
was smaller but significantly larger than the amount of within-listener
variability, which represented the smallest effect. The results have implications
for the design of consonant perception experiments and provide constraints for
future models of consonant perception.
PMID- 26428765
TI - Environmentally adaptive processing for shallow ocean applications: A sequential
Bayesian approach.
AB - The shallow ocean is a changing environment primarily due to temperature
variations in its upper layers directly affecting sound propagation throughout.
The need to develop processors capable of tracking these changes implies a
stochastic as well as an environmentally adaptive design. Bayesian techniques
have evolved to enable a class of processors capable of performing in such an
uncertain, nonstationary (varying statistics), non-Gaussian, variable shallow
ocean environment. A solution to this problem is addressed by developing a
sequential Bayesian processor capable of providing a joint solution to the modal
function tracking and environmental adaptivity problem. Here, the focus is on the
development of both a particle filter and an unscented Kalman filter capable of
providing reasonable performance for this problem. These processors are applied
to hydrophone measurements obtained from a vertical array. The adaptivity problem
is attacked by allowing the modal coefficients and/or wavenumbers to be jointly
estimated from the noisy measurement data along with tracking of the modal
functions while simultaneously enhancing the noisy pressure-field measurements.
PMID- 26428766
TI - Modeling photoacoustic cavitation nucleation and bubble dynamics with modified
classical nucleation theory.
AB - Photoacoustic cavitation (PAC) is the formation of bubbles in liquids using a
focused laser and a pre-established ultrasound synchronously. The decreased
threshold of each modality and the precise location of cavitation determined by
the focused laser are both significant in the targeted theranostics. In this
study, PAC nucleation was described using the modified classical nucleation
theory by Kashchiev's scaling function. A two-stage model of the PAC bubble
dynamics was presented based on the two different bubble behaviors. It was
clarified that both negative acoustic pressure and laser-induced temperature
rise, resulting in the decrease in critical radius and the increase in nucleation
rate, and thereby contribute to the increase in nucleation probability in the
confocal region. Ultrasound determined the whole PAC bubble dynamics with
temperature-dependent parameters, while the laser mainly contributed to its
initial conditions. Moreover, the effects of certain parameters on PAC were
further discussed, including the relative acoustic phase when a laser is
introduced (phi), laser pulse duration (tau(L)), laser focus radius (R(f)), and
ultrasound amplitude (P(A)). The model would be helpful in understanding the PAC
process and further in introducing PAC to potential targeted theranostics.
PMID- 26428768
TI - Enhancing listener strategies using a payoff matrix in speech-on-speech masking
experiments.
AB - Speech recognition was measured as a function of the target-to-masker ratio (TMR)
with syntactically similar speech maskers. In the first experiment, listeners
were instructed to report keywords from the target sentence. Data averaged across
listeners showed a plateau in performance below 0 dB TMR when masker and target
sentences were from the same talker. In this experiment, some listeners tended to
report the target words at all TMRs in accordance with the instructions, while
others reported keywords from the louder of the sentences, contrary to the
instructions. In the second experiment, stimuli were the same as in the first
experiment, but listeners were also instructed to avoid reporting the masker
keywords, and a payoff matrix penalizing masker keywords and rewarding target
keywords was used. In this experiment, listeners reduced the number of reported
masker keywords, and increased the number of reported target keywords overall,
and the average data showed a local minimum at 0 dB TMR with same-talker maskers.
The best overall performance with a same-talker masker was obtained with a level
difference of 9 dB, where listeners achieved near perfect performance when the
target was louder, and at least 80% correct performance when the target was the
quieter of the two sentences.
PMID- 26428769
TI - The acoustic structure of male giant panda bleats varies according to intersexual
context.
AB - Although the acoustic structure of mammal vocal signals often varies according to
the social context of emission, relatively few mammal studies have examined
acoustic variation during intersexual advertisement. In the current study male
giant panda bleats were recorded during the breeding season in three behavioural
contexts: vocalising alone, during vocal interactions with females outside of
peak oestrus, and during vocal interactions with peak-oestrous females. Male
bleats produced during vocal interactions with peak-oestrous females were longer
in duration and had higher mean fundamental frequency than those produced when
males were either involved in a vocal interaction with a female outside of peak
oestrus or vocalising alone. In addition, males produced bleats with higher rates
of fundamental frequency modulation when they were vocalising alone than when
they were interacting with females. These results show that acoustic features of
male giant panda bleats have the potential to signal the caller's motivational
state, and suggest that males increase the rate of fundamental frequency
modulation in bleats when they are alone to maximally broadcast their quality and
promote close-range contact with receptive females during the breeding season.
PMID- 26428770
TI - Near-field sound radiation of fan tones from an installed turbofan aero-engine.
AB - The development of a distributed source model to predict fan tone noise levels of
an installed turbofan aero-engine is reported. The key objective is to examine a
canonical problem: how to predict the pressure field due to a distributed source
located near an infinite, rigid cylinder. This canonical problem is a simple
representation of an installed turbofan, where the distributed source is based on
the pressure pattern generated by a spinning duct mode, and the rigid cylinder
represents an aircraft fuselage. The radiation of fan tones can be modelled in
terms of spinning modes. In this analysis, based on duct modes, theoretical
expressions for the near-field acoustic pressures on the cylinder, or at the same
locations without the cylinder, have been formulated. Simulations of the near
field acoustic pressures are compared against measurements obtained from a fan
rig test. Also, the installation effect is quantified by calculating the
difference in the sound pressure levels with and without the adjacent cylindrical
fuselage. Results are shown for the blade passing frequency fan tone radiated at
a supersonic fan operating condition.
PMID- 26428771
TI - Waveform modeling and inversion of ambient noise cross-correlation functions in a
coastal ocean environment.
AB - Theoretical studies have shown that cross-correlation functions (CFs) of time
series of ambient noise measured at two locations yield approximations to the
Green's functions (GFs) that describe propagation between those locations.
Specifically, CFs are estimates of weighted GFs. In this paper, it is
demonstrated that measured CFs in the 20-70 Hz band can be accurately modeled as
weighted GFs using ambient noise data collected in the Florida Straits at ~100 m
depth with horizontal separations of 5 and 10 km. Two weighting functions are
employed. These account for (1) the dipole radiation pattern produced by a near
surface source, and (2) coherence loss of surface-reflecting energy in time
averaged CFs resulting from tidal fluctuations. After describing the relationship
between CFs and GFs, the inverse problem is considered and is shown to result in
an environmental model for which agreement between computed and simulated CFs is
good.
PMID- 26428772
TI - Effect of horizontal wave barriers on ground vibration propagation.
AB - The aim of this article is to introduce a method to mitigate ground surface
vibration through a flexural plate coupled to the ground and acting as a
horizontal wave barrier. Using the thin plate hypothesis, two flexural plates are
coupled to the ground, the first plate being the excited plate and the second
plate the horizontal wave barrier. For instance, the first plate may represent a
slab track and be excited by the tramway wheels. A solution to the problem can be
found using a spatial two-dimensional Fourier transform of the elastodynamics
equation for the ground and a modal decomposition for the flexural plate
vibration. The authors show that vibration is substantially mitigated by the
horizontal wave barrier and depends on its thickness and width. When the top
surface wavelength becomes smaller than twice the plate width, the horizontal
wave barrier acts as a wave barrier in the frequency range of interest, i.e.,
from 20 Hz.
PMID- 26428773
TI - Echolocation signals of free-ranging Indo-Pacific humpback dolphins (Sousa
chinensis) in Sanniang Bay, China.
AB - While the low-frequency communication sounds of Indo-Pacific humpback dolphins
(Sousa chinensis) have been reported in a number of papers, the high-frequency
echolocation signals of Sousa chinensis, especially those living in the wild,
have been less studied. In the current study, echolocation signals of humpback
dolphins were recorded in Sanniang Bay, Guangxi Province, China, using a cross
type hydrophone array with five elements. In total, 77 candidate on-axis clicks
from 77 scans were selected for analysis. The results showed that the varied peak
to-peak source levels ranged from 177.1 to 207.3 dB, with an average of 187.7 dB
re: 1 MUPa. The mean peak frequency was 109.0 kHz with a -3-dB bandwidth of 50.3
kHz and 95% energy duration of 22 MUs. The -3-dB bandwidth was much broader than
the root mean square bandwidth and exhibited a bimodal distribution. The center
frequency exhibited a positive relationship with the peak-to-peak source level.
The clicks of the wild Indo-Pacific humpback dolphins were short-duration,
broadband, ultrasonic pulses, similar to those produced by other whistling
dolphins of similar body size. However, the click source levels of the Indo
Pacific humpback dolphin appear to be lower than those of other whistling
dolphins.
PMID- 26428774
TI - Entropy rate defined by internal wave scattering in long-range propagation.
AB - The reduction of information capacity of the ocean sound channel due to
scattering by internal waves is a potential problem for acoustic communication,
navigation, and remote sensing over long ranges. In spite of recent progress in
research on acoustic signal scattering by random internal waves and the fact that
random internal waves are ubiquitous in the world oceans, there is no clear
understanding of how these waves influence data communication performance. The
entropy decrease resulting from scattering by internal waves is an important
measure of information loss. Here a rigorous calculation of the entropy is
carried out using second moment transport theory equations with random sound
speed perturbations obeying the Garrett-Munk internal-wave model. It is shown
that full-wave rate of entropy is of the same order of magnitude as the
Kolmogorov-Sinai entropy and Lyapunov exponents for the relevant ray
trajectories. The correspondence between full-wave and ray entropies suggests a
correspondence between full-wave scattering and ray chaos near statistical
saturation. The relatively small level of entropy rate during propagation through
the random internal-wave field shows that scattering by internal waves is likely
not an essential limitation for data rate and channel capacity.
PMID- 26428775
TI - Reconstruction of specular reflectors by iterative image source localization.
AB - A method is presented to reconstruct the geometry of specular reflectors with an
ultrasonic array based on the image source principle. The ultrasonic beam is
focused at a point in space emulating a point source within the medium. The
transmitted wave interacts with the specular reflector and propagates back to the
array as if it were generated by an image source. The reflected wave is analyzed
with a sound source localization algorithm to estimate the image source location,
and the reflector geometry is extracted using the mirror equation for spherical
reflectors. The method is validated experimentally and its accuracy is studied.
Under ideal conditions the method provides an accurate reconstruction of the
position, orientation, and radius of curvature of specular reflectors, with
errors Deltar < 0.2 mm, Deltaalpha < 3 degrees , and DeltaR/R0 < 0.2,
respectively. The method performs very well in the presence of high levels of
thermal and speckle noise, with no degradation of the reconstruction as long as
SNR(th) > -3 dB (signal-to-thermal-noise ratio) and SNR(sp) > 7 dB (signal-to
speckle-noise ratio). An iterative scheme based on the proposed method is
presented to reconstruct the geometry of arbitrary reflectors by subdividing the
reflector boundary into smaller segments. The iterative scheme is demonstrated
both numerically and experimentally.
PMID- 26428776
TI - Description and seasonal detection of two potential whale calls recorded in the
Indian Ocean.
AB - Unidentified acoustic signals are recorded by hydrophones placed in the world's
oceans. Some of these sounds are suspected to originate from marine mammals. In
this study, two acoustic signals recorded by two arrays at Diego Garcia in the
northern Indian Ocean are described. Data were available between January 2002 and
December 2003. Signals were detected manually using long-term spectral average
plots. Time and frequency measurements were taken from a sample of both signals.
The first unidentified signal [Diego Garcia Downsweep (DGD)] consisted of two
main components. The mean frequency range of the entire signal was 19.3-45.0 Hz,
with a mean duration of 36.5 s (n = 22). Detections of DGD at the northern array
peaked in the austral summer, though detections at the southern array peaked
during winter and spring. The second unidentified signal [Diego Garcia Croak
(DGC)] consisted of one component with a mean frequency range of 16.9-49.6 Hz.
The mean duration of the signal was 13.1 s (n = 10). Detections of DGC did not
follow a clear seasonal pattern. These signals followed characteristics of
biological sources, suggesting that they could be whale calls. Fin whale calls
and possible blue whales D-calls were also identified in the data.
PMID- 26428777
TI - Time-varying feedback matrices in feedback delay networks and their application
in artificial reverberation.
AB - This paper introduces a time-variant reverberation algorithm as an extension of
the feedback delay network (FDN). By modulating the feedback matrix nearly
continuously over time, a complex pattern of concurrent amplitude modulations of
the feedback paths evolves. Due to its complexity, the modulation produces less
likely perceivable artifacts and the time-variation helps to increase the
liveliness of the reverberation tail. A listening test, which has been conducted,
confirms that the perceived quality of the reverberation tail can be enhanced by
the feedback matrix modulation. In contrast to the prior art time-varying allpass
FDNs, it is shown that unitary feedback matrix modulation is guaranteed to be
stable. Analytical constraints on the pole locations of the FDN help to describe
the modulation effect in depth. Further, techniques and conditions for continuous
feedback matrix modulation are presented.
PMID- 26428778
TI - Estimating nonnegative matrix model activations with deep neural networks to
increase perceptual speech quality.
AB - As a means of speech separation, time-frequency masking applies a gain function
to the time-frequency representation of noisy speech. On the other hand,
nonnegative matrix factorization (NMF) addresses separation by linearly combining
basis vectors from speech and noise models to approximate noisy speech. This
paper presents an approach for improving the perceptual quality of speech
separated from background noise at low signal-to-noise ratios. An ideal ratio
mask is estimated, which separates speech from noise with reasonable sound
quality. A deep neural network then approximates clean speech by estimating
activation weights from the ratio-masked speech, where the weights linearly
combine elements from a NMF speech model. Systematic comparisons using objective
metrics, including the perceptual evaluation of speech quality, show that the
proposed algorithm achieves higher speech quality than related masking and NMF
methods. In addition, a listening test was performed and its results show that
the output of the proposed algorithm is preferred over the comparison systems in
terms of speech quality.
PMID- 26428779
TI - Age and hearing loss and the use of acoustic cues in fricative categorization.
AB - This study examined the use of fricative noise information and coarticulatory
cues for categorization of word-final fricatives [s] and [f] by younger and older
Dutch listeners alike. Particularly, the effect of information loss in the higher
frequencies on the use of these two cues for fricative categorization was
investigated. If information in the higher frequencies is less strongly
available, fricative identification may be impaired or listeners may learn to
focus more on coarticulatory information. The present study investigates this
second possibility. Phonetic categorization results showed that both younger and
older Dutch listeners use the primary cue fricative noise and the secondary cue
coarticulatory information to distinguish word-final [f] from [s]. Individual
hearing sensitivity in the older listeners modified the use of fricative noise
information, but did not modify the use of coarticulatory information. When high
frequency information was filtered out from the speech signal, fricative noise
could no longer be used by the younger and older adults. Crucially, they also did
not learn to rely more on coarticulatory information as a compensatory cue for
fricative categorization. This suggests that listeners do not readily show
compensatory use of this secondary cue to fricative identity when fricative
categorization becomes difficult.
PMID- 26428780
TI - Temporal effects in priming of masked and degraded speech.
AB - When listeners know the content of the message they are about to hear, the
clarity of distorted or partially masked speech increases dramatically. The
current experiments investigated this priming phenomenon quantitatively using a
same-different task where a typed caption and auditory message either matched
exactly or differed by one key word. Four conditions were tested with groups of
normal-hearing listeners: (a) natural speech presented in two-talker babble in a
non-spatial configuration, (b) same as (a) but with the masker time reversed, (c)
same as (a) but with target-masker spatial separation, and (d) vocoded sentences
presented in speech-spectrum noise. The primary manipulation was the timing of
the caption relative to the auditory message, which varied in 20 steps with a
resolution of 200 ms. Across all four conditions, optimal performance was
achieved when the initiation of the text preceded the acoustic speech signal by
at least 400 ms, driven mostly by a low number of "different" responses to Same
stimuli. Performance was slightly poorer with simultaneous delivery and much
poorer when the auditory signal preceded the caption. Because priming may be used
to facilitate perceptual learning, identifying optimal temporal conditions for
priming could help determine the best conditions for auditory training.
PMID- 26428782
TI - Tissue physical property of the harbor porpoise Phocoena phocoena for
investigation of the sound emission process.
AB - The process by which sound is propagated in the head of a toothed whale is still
a subject of discussion. Investigating the distribution of acoustic impedance
calculated by density and Young's modulus is effective for quantitative
comprehension because acoustic impedance determines the reflection coefficient of
a sound wave. However, the sound propagation process of the toothed whale has
been mainly examined by either anatomical techniques or the measurement of
density or sound velocity. In the current study, the acoustic impedance of head
tissue of harbor porpoise was measured. Results of this study should be a helpful
information for further discussion about the relationship between the structure
of sound-producing organ and clicks property.
PMID- 26428783
TI - Development and validation of a combined phased acoustical radiosity and image
source model for predicting sound fields in rooms.
AB - A model, combining acoustical radiosity and the image source method, including
phase shifts on reflection, has been developed. The model is denoted Phased
Acoustical Radiosity and Image Source Method (PARISM), and it has been developed
in order to be able to model both specular and diffuse reflections with complex
valued and angle-dependent boundary conditions. This paper mainly describes the
combination of the two models and the implementation of the angle-dependent
boundary conditions. It furthermore describes how a pressure impulse response is
obtained from the energy-based acoustical radiosity by regarding the model as
being stochastic. Three methods of implementation are proposed and investigated,
and finally, recommendations are made for their use. Validation of the image
source method is done by comparison with finite element simulations of a
rectangular room with a porous absorber ceiling. Results from the full model are
compared with results from other simulation tools and with measurements. The
comparisons of the full model are done for real-valued and angle-independent
surface properties. The proposed model agrees well with both the measured results
and the alternative theories, and furthermore shows a more realistic spatial
variation than energy-based methods due to the fact that interference is
considered.
PMID- 26428785
TI - Dependency of resonance frequencies and effective coupling coefficients of
piezoceramic rectangular bars and plates on aspect ratio.
AB - The resonance frequencies and effective coupling coefficients of piezoceramic
rectangular plates polarized through their width and transversely polarized bars
are presented as functions of their lateral aspect ratios. The results are
obtained by employing the coupled vibration analysis technique that was
previously illustrated for rectangular plates polarized through the thickness [J.
Acoust. Soc. Am. 126(6), 2983-2990 (2009)]. The results of calculations show good
agreement with experimental data. Conclusions are made on preferable values of
the aspect ratios in terms of the effective coupling coefficients.
PMID- 26428784
TI - Dual-carrier processing to convey temporal fine structure cues: Implications for
cochlear implants.
AB - Speech intelligibility in noise can be degraded by using vocoder processing to
alter the temporal fine structure (TFS). Here it is argued that this degradation
is not attributable to the loss of speech information potentially present in the
TFS. Instead it is proposed that the degradation results from the loss of sound
source segregation information when two or more carriers (i.e., TFS) are
substituted with only one as a consequence of vocoder processing. To demonstrate
this segregation role, vocoder processing involving two carriers, one for the
target and one for the background, was implemented. Because this approach does
not preserve the speech TFS, it may be assumed that any improvement in
intelligibility can only be a consequence of the preserved carrier duality and
associated segregation cues. Three experiments were conducted using this "dual
carrier" approach. All experiments showed substantial sentence intelligibility in
noise improvements compared to traditional single-carrier conditions. In several
conditions, the improvement was so substantial that intelligibility approximated
that for unprocessed speech in noise. A foreseeable and potentially promising
implication for the dual-carrier approach involves implementation into cochlear
implant speech processors, where it may provide the TFS cues necessary to
segregate speech from noise.
PMID- 26428786
TI - Objective and perceptual assessment of the scattered sound field in a simulated
concert hall.
AB - Acoustic scattering audibility thresholds are needed for the efficient design of
performance spaces and to increase the accuracy of geometric room acoustic
models. This paper focuses on the evaluation of the perceptual thresholds of the
scattering coefficient through listening tests in simulated concert halls. It
also deals with an investigation on the sensitivity of room acoustic parameters
to scattering coefficients. A rectangular concert hall has been simulated with
three prediction models, in which scattering coefficients of 0.1, 0.3, 0.5, 0.6,
0.7, and 0.9 were applied to the ceiling and walls in six different
configurations. The analysis was performed comparing the results of the three
alternative forced choice listening tests and considering the objective
parameters T30, early decay time (EDT), C80, and G. An increase in EDT and a
decrease in C80 have been observed for increasing scattering coefficient values
for all three types of software, while no similar trend was observed for the
other parameters. The perceptual evaluation has shown that differences of ~0.4,
relative to an anchor value of 0.9 of the scattering coefficient, were perceived
in the listening test conducted with one of the three kinds of software, while no
clear differences in auralizations were perceived with the other two kinds.
PMID- 26428787
TI - On the acoustoelasticity of polycrystalline materials.
AB - A linear relation between the strains and stresses of a crystallite within a
polycrystal is used to homogenize the polycrystal's elastic properties. The
homogenization parallels the self-consistent method that is used for estimating
the polycrystal's linear elastic properties. Acoustoelasticity for a
macroscopically isotropic polycrystal is then formulated using a homogenized
constitutive equation with initial stress. Simple expressions are given for the
phase velocities and polarization directions for a uniaxially stressed
polycrystal. The present model is compared with the model of Man and Paroni [J.
Elast. 45, 91-116 (1996)]. Strong anisotropy of the crystallite elastic constants
causes the present model to differ noticeably from the model of Man and Paroni.
PMID- 26428788
TI - The effect of stimulus bandwidth on binaural loudness summation.
AB - Binaural loudness summation is an important property of the human auditory
system. This paper presents an experimental investigation of how binaural
loudness summation varies with stimulus bandwidth. Loudness matches were obtained
between dichotic stimuli, with interaural level differences (ILDs) of 2-12 dB,
and diotic stimuli. The stimuli were noise bands with seven center frequencies
and four bandwidths. Results showed that the loudness of dichotic stimuli
increased nonlinearly with ILD, the increase being slightly less with broader
bandwidths. There was a bandwidth-dependent difference between the listening
tests results and the predictions of Moore and Glasberg's [(2007) J. Acoust. Soc.
Am. 121, 1604-1612] loudness model. The size of the difference was, however,
small. A characteristic function was derived describing how overall loudness
depends on stimulus bandwidth and ILD.
PMID- 26428789
TI - Acoustic holography as a metrological tool for characterizing medical ultrasound
sources and fields.
AB - Acoustic holography is a powerful technique for characterizing ultrasound sources
and the fields they radiate, with the ability to quantify source vibrations and
reduce the number of required measurements. These capabilities are increasingly
appealing for meeting measurement standards in medical ultrasound; however,
associated uncertainties have not been investigated systematically. Here errors
associated with holographic representations of a linear, continuous-wave
ultrasound field are studied. To facilitate the analysis, error metrics are
defined explicitly, and a detailed description of a holography formulation based
on the Rayleigh integral is provided. Errors are evaluated both for simulations
of a typical therapeutic ultrasound source and for physical experiments with
three different ultrasound sources. Simulated experiments explore sampling errors
introduced by the use of a finite number of measurements, geometric uncertainties
in the actual positions of acquired measurements, and uncertainties in the
properties of the propagation medium. Results demonstrate the theoretical
feasibility of keeping errors less than about 1%. Typical errors in physical
experiments were somewhat larger, on the order of a few percent; comparison with
simulations provides specific guidelines for improving the experimental
implementation to reduce these errors. Overall, results suggest that holography
can be implemented successfully as a metrological tool with small, quantifiable
errors.
PMID- 26428790
TI - The influence of proscenium boxes on acoustic response in historical opera halls.
AB - In some historical opera halls there are boxes located around the proscenium,
commonly called proscenium or "director" boxes. These boxes have a certain
influence on the initial part of the impulse response of an opera hall on the
singer-auditorium, singer-singer, and singer-orchestra pit paths. During the
reconstruction of the Ljubljana opera hall, measurement of a scaled model was
performed to quantify the influence of proscenium boxes on the hall's impulse
response. Some variation in box configuration on the acoustic response was also
tested. This paper describes the results of this research.
PMID- 26428791
TI - Difference in electrodynamic transduction between speaker and alternator in
thermoacoustic applications.
AB - Conventional reciprocating pistons, normally found in thermoacoustic engines,
tend to introduce complex impedance characteristics, including acoustic,
mechanical, and electrical portions. System behavior and performance usually rely
on proper tuning processes and selection of an optimal point of operation,
affected substantially by complementary hardware, typically adjusted for the
specific application. The present study proposes an alternative perspective on
the alternator behavior, by considering the relative motion between gas and
piston during the engine mode of operation. Direct analytical derivation of the
velocity distribution inside a tight seal gap and the associated impedance is
employed to estimate the electro-acoustic conversion efficiency, thus indicating
how to improve the system performance. The influence of acoustic phase, gap
dimensions, and working conditions is examined, suggesting the need to develop
tighter and longer seal gaps, having increased impedance, to allow optimization
for use in upcoming sustainable power generation solutions and smart grids.
PMID- 26428792
TI - Computing interaural differences through finite element modeling of idealized
human heads.
AB - Acoustical interaural differences were computed for a succession of idealized
shapes approximating the human head-related anatomy: sphere, ellipsoid, and
ellipsoid with neck and torso. Calculations were done as a function of frequency
(100-2500 Hz) and for source azimuths from 10 to 90 degrees using finite element
models. The computations were compared to free-field measurements made with a
manikin. Compared to a spherical head, the ellipsoid produced greater large-scale
variation with frequency in both interaural time differences and interaural level
differences, resulting in better agreement with the measurements. Adding a torso,
represented either as a large plate or as a rectangular box below the neck,
further improved the agreement by adding smaller-scale frequency variation. The
comparisons permitted conjectures about the relationship between details of
interaural differences and gross features of the human anatomy, such as the
height of the head, and length of the neck.
PMID- 26428794
TI - Nonuniform piezoelectric circular plate flexural transducers with underwater
applications.
AB - An analytical treatment is presented for circular flexural plate transducers that
have nonuniform electromechanically active-passive mechanical systems with
particular interest in underwater applications. The analysis is made using the
energy method that was previously applied to calculating parameters of uniform
fully active (bimorph) circular plate transducers [B. S. Aronov, J. Acoust. Soc.
Am. 118(2), 627-637 (2005)]. It is shown that the vibration mode shapes remain
sufficiently similar to those for uniform plates for a large range of relative
dimensions of active and passive laminates of radially nonuniform mechanical
systems, and they may be used for calculating transducer parameters. Therefore
the transducers can be considered as having a single degree of freedom, and their
operational characteristics can be determined using the same technique as
previously used for uniform plates. Dependences of the resonance frequencies,
effective coupling coefficients, and parameters of the equivalent
electromechanical circuit on relative dimensions of active and passive laminates
for several combinations of the active and passive materials are presented and
compared with those parameters of uniform plates having the same overall
dimensions. The results of experimental verification are in good agreement with
theoretical predictions.
PMID- 26428793
TI - Memory disruption by irrelevant noise-vocoded speech: Effects of native language
and the number of frequency bands.
AB - To investigate the mechanisms by which unattended speech impairs short-term
memory performance, speech samples were systematically degraded by means of a
noise vocoder. For experiment 1, recordings of German and Japanese sentences were
passed through a filter bank dividing the spectrum between 50 and 7000 Hz into 20
critical-band channels or combinations of those, yielding 20, 4, 2, or just 1
channel(s) of noise-vocoded speech. Listening tests conducted with native
speakers of both languages showed a monotonic decrease in speech intelligibility
as the number of frequency channels was reduced. For experiment 2, 40 native
German and 40 native Japanese participants were exposed to speech processed in
the same manner while trying to memorize visually presented sequences of digits
in the correct order. Half of each sample received the German, the other half
received the Japanese speech samples. The results show large irrelevant-speech
effects increasing in magnitude with the number of frequency channels. The
effects are slightly larger when subjects are exposed to their own native
language. The results are neither predicted very well by the speech transmission
index, nor by psychoacoustical fluctuation strength, most likely, since both
metrics fail to disentangle amplitude and frequency modulations in the signals.
PMID- 26428796
TI - Characterization of the complexity in short oscillating time series: An
application to seismic airgun detonations.
AB - Extracting frequency-derived parameters allows for the identification and
characterization of acoustic events, such as those obtained in passive acoustic
monitoring applications. Situations where it is difficult to achieve the desired
frequency resolution to distinguish between similar events occur, for example, in
short time oscillating events. One feasible approach to make discrimination among
such events is by measuring the complexity or the presence of non-linearities in
a time series. Available techniques include the delay vector variance (DVV) and
recurrence plot (RP) analysis, which have been used independently for statistical
testing, however, the similarities between these two techniques have so far been
overlooked. This work suggests a method that combines the DVV method with the
recurrence quantification analysis parameters of the RP graphs for the
characterization of short oscillating events. In order to establish the
confidence intervals, a variant of the pseudo-periodic surrogate algorithm is
proposed. This allows one to eliminate the fine details that may indicate the
presence of non-linear dynamics, without having to add a large amount of noise,
while preserving more efficiently the phase-space shape. The algorithm is
verified on both synthetic and real world time series.
PMID- 26428795
TI - A modified sequential algebraic algorithm applied to identify rough acoustic
impedance profiles in slender structures.
AB - This paper develops and examines a modified technique for identifying damage in
slender structures. An algorithm, called modified sequential algebraic algorithm,
is presented to solve the longitudinal acoustic wave propagation problem in
inhomogeneous media. This method accurately predicts the echo generated by the
inhomogeneities when the acoustic impedance variation profile in the damaged part
of the structure is non-smooth. For these cases, the available algorithms fail to
provide the actual regressive wave component. In the following, a stochastic
optimization scheme, the differential evolution method, is applied to solve the
inverse problem. Numerical examples with smooth and non-smooth impedance profiles
are considered. It is shown that, for smooth profiles, both the available
techniques and the modified algorithm succeed in identifying the actual damage.
Nevertheless, in situations where a rough profile is to be reconstructed, only
the modified algorithm succeeds. The technique is found to be robust with respect
to additive noise in the signals.
PMID- 26428798
TI - An integral equation method for calculating sound field diffracted by a rigid
barrier on an impedance ground.
AB - This paper proposes a different method for calculating a sound field diffracted
by a rigid barrier based on the integral equation method, where a virtual
boundary is assumed above the rigid barrier to divide the whole space into two
subspaces. Based on the Kirchhoff-Helmholtz equation, the sound field in each
subspace is determined with the source inside and the boundary conditions on the
surface, and then the diffracted sound field is obtained by using the
continuation conditions on the virtual boundary. Simulations are carried out to
verify the feasibility of the proposed method. Compared to the MacDonald method
and other existing methods, the proposed method is a rigorous solution for whole
space and is also much easier to understand.
PMID- 26428800
TI - Acoustic analysis of the frequency-dependent coupling between the frog's ears.
AB - The ears of anurans are coupled through the Eustachian tubes and mouth cavity.
The degree of coupling varies with frequency showing a bandpass characteristic,
but the characteristics differ between empirically measured data based on
auditory nerve responses and tympanic membrane vibration. In the present study,
the coupling was modeled acoustically as a tube connected with a side branch.
This tube corresponds to the Eustachian tubes, whereas the side branch
corresponds to the mouth cavity and nares. The analysis accounts for the
frequency dependency shown by the empirical data and reconciles the differences
observed between the coupling as measured by tympanic membrane vibration and
auditory nerve responses.
PMID- 26428799
TI - Individual and sex distinctiveness in bark calls of domestic chinchillas elicited
in a distress context.
AB - Animals obtain information about their social environment by means of
communication signals, which provide relevant subtle cues for individual
recognition. An important requisite for this process is the existence of larger
between- than within-emitter signal variation. Acoustic signals are complex
traits susceptible of variation in their spectral and temporal components,
implying that signal distinctiveness can result from differences in single or
various acoustic components. In this study, domestic chinchillas were induced to
vocalize in a distress context to describe the acoustic characteristics of the
bark calls, and to determine features that denote the potential value of this
vocalization for individual and/or sexual recognition. The results demonstrate
that the variation in spectral and temporal components of the bark calls of
chinchillas elicited under a distress context is larger between than within
individuals, suggesting the potential of these signals for distinctiveness
between individual signalers, although the potential of this call type for sex
distinctiveness is quite limited. These results combined with previous studies on
auditory capabilities of chinchillas contribute to position this rodent as a
valuable model species for studying auditory-vocal interactions.
PMID- 26428801
TI - Acousto-optic effect compensation for optical determination of the normal
velocity distribution associated with acoustic transducer radiation.
AB - The acousto-optic effect, in which an acoustic wave causes variations in the
optical index of refraction, imposes a fundamental limitation on the
determination of the normal velocity, or normal displacement, distribution on the
surface of an acoustic transducer or optically reflecting pellicle by a scanning
heterodyne, or homodyne, laser interferometer. A general method of compensation
is developed for a pulsed harmonic pressure field, transmitted by an acoustic
transducer, in which the laser beam can transit the transducer nearfield. By
representing the pressure field by the Rayleigh integral, the basic equation for
the unknown normal velocity on the surface of the transducer or pellicle is
transformed into a Fredholm equation of the second kind. A numerical solution is
immediate when the scanned points on the surface correspond to those of the
surface area discretization. Compensation is also made for oblique angles of
incidence by the scanning laser beam. The present compensation method neglects
edge waves, or those due to boundary diffraction, as well as effects due to
baffles, if present. By allowing measurement in the nearfield of the radiating
transducer, the method can enable quantification of edge-wave and baffle effects
on transducer radiation. A verification experiment has been designed.
PMID- 26428803
TI - An algorithm to increase speech intelligibility for hearing-impaired listeners in
novel segments of the same noise type.
AB - Machine learning algorithms to segregate speech from background noise hold
considerable promise for alleviating limitations associated with hearing
impairment. One of the most important considerations for implementing these
algorithms into devices such as hearing aids and cochlear implants involves their
ability to generalize to conditions not employed during the training stage. A
major challenge involves the generalization to novel noise segments. In the
current study, sentences were segregated from multi-talker babble and from
cafeteria noise using an algorithm that employs deep neural networks to estimate
the ideal ratio mask. Importantly, the algorithm was trained on segments of noise
and tested using entirely novel segments of the same nonstationary noise type.
Substantial sentence-intelligibility benefit was observed for hearing-impaired
listeners in both noise types, despite the use of unseen noise segments during
the test stage. Interestingly, normal-hearing listeners displayed benefit in
babble but not in cafeteria noise. This result highlights the importance of
evaluating these algorithms not only in human subjects, but in members of the
actual target population.
PMID- 26428802
TI - Functional modeling of the human auditory brainstem response to broadband
stimulation.
AB - Population responses such as the auditory brainstem response (ABR) are commonly
used for hearing screening, but the relationship between single-unit physiology
and scalp-recorded population responses are not well understood. Computational
models that integrate physiologically realistic models of single-unit auditory
nerve (AN), cochlear nucleus (CN) and inferior colliculus (IC) cells with models
of broadband peripheral excitation can be used to simulate ABRs and thereby link
detailed knowledge of animal physiology to human applications. Existing
functional ABR models fail to capture the empirically observed 1.2-2 ms ABR wave
V latency-vs-intensity decrease that is thought to arise from level-dependent
changes in cochlear excitation and firing synchrony across different tonotopic
sections. This paper proposes an approach where level-dependent cochlear
excitation patterns, which reflect human cochlear filter tuning parameters, drive
AN fibers to yield realistic level-dependent properties of the ABR wave-V. The
number of free model parameters is minimal, producing a model in which various
sources of hearing-impairment can easily be simulated on an individualized and
frequency-dependent basis. The model fits latency-vs-intensity functions observed
in human ABRs and otoacoustic emissions while maintaining rate-level and
threshold characteristics of single-unit AN fibers. The simulations help to
reveal which tonotopic regions dominate ABR waveform peaks at different stimulus
intensities.
PMID- 26428805
TI - Source depth estimation based on synthetic aperture beamfoming for a moving
source.
AB - A continuous wave signal received on a single hydrophone from a moving source is
beamformed using the synthetic aperture created by the source, where the signal
at each range is steered by a range-dependent phase, relative to the starting
point. The range increment (aperture) is determined based on the Doppler shift
estimated from the data, knowing the original signal frequency. Given a
sufficient signal-to-noise ratio, the source depth can be estimated from the beam
output, assuming knowledge of the mode depth functions based on the nominal sound
speed and bottom profile in the area. The method is illustrated with simulated
data and at-sea data. For real data, the signal phase contains a random,
incoherent component caused by the (random) source motion and media fluctuations
in addition to the deterministic range-dependent component due to source range
change. A phase locked loop is introduced to remove the random component assuming
that the random component fluctuates faster with time than the range-dependent
phase. When a vertical array of receivers are available covering the depth span
of interest, the beam output can be used directly to estimate the source depth.
In this case, no knowledge of the acoustic environment is needed.
PMID- 26428804
TI - Vowel identification in temporal-modulated noise for native and non-native
listeners: Effect of language experience.
AB - A previous study found that English vowel identification in babble was
significantly different between Chinese-native listeners in China and in the U.S.
One possible explanation is that native English experiences might change Chinese
native listeners' ability to take advantage of the temporal modulation in noise
for their English vowel perception. As a follow-up, the current study explored
whether there was a difference between the two groups of Chinese listeners in
using temporal gaps in noise for English vowel identification. Vowel
identification in temporally modulated noise and a temporal modulation transfer
function (TMTF) was measured for American-English-native listeners (EN), Chinese
native listeners in the U.S. (CNU), and Chinese-native listeners in China (CNC).
The results revealed that TMTFs were similar across the three groups, indicating
that psychophysical temporal processing was independent of listeners' language
backgrounds. However, for vowel identification in noise, EN and CNU listeners
showed significantly greater masking release from the temporal modulation of
noise than CNC listeners at low signal-to-noise ratios (e.g., -12 dB).
Altogether, native English experiences may change the use of temporal cues in
noise for English vowel identification for Chinese-native listeners.
PMID- 26428806
TI - Fundamental-frequency discrimination using noise-band-vocoded harmonic complexes
in older listeners with normal hearing.
AB - Voice-pitch cues provide detailed information about a talker that help a listener
to understand speech in complex environments. Temporal-envelope based voice-pitch
coding is important for listeners with hearing impairment, especially listeners
with cochlear implants, as spectral resolution is not sufficient to provide a
spectrally based voice-pitch cue. The effect of aging on the ability to glean
voice-pitch information using temporal envelope cues is not completely
understood. The current study measured fundamental frequency (f0) discrimination
limens in normal-hearing younger and older adults while listening to noise-band
vocoded harmonic complexes with varying numbers of spectral channels. Age-related
disparities in performance were apparent across all conditions, independent of
spectral degradation and/or fundamental frequency. The findings have important
implications for older listeners with normal hearing and hearing loss, who may be
inherently limited in their ability to perceive f0 cues due to senescent decline
in auditory function.
PMID- 26428808
TI - Noise-induced hearing loss in marine mammals: A review of temporary threshold
shift studies from 1996 to 2015.
AB - One of the most widely recognized effects of intense noise exposure is a noise
induced threshold shift-an elevation of hearing thresholds following cessation of
the noise. Over the past twenty years, as concerns over the potential effects of
human-generated noise on marine mammals have increased, a number of studies have
been conducted to investigate noise-induced threshold shift phenomena in marine
mammals. The experiments have focused on measuring temporary threshold shift
(TTS)-a noise-induced threshold shift that fully recovers over time-in marine
mammals exposed to intense tones, band-limited noise, and underwater impulses
with various sound pressure levels, frequencies, durations, and temporal
patterns. In this review, the methods employed by the groups conducting marine
mammal TTS experiments are described and the relationships between the
experimental conditions, the noise exposure parameters, and the observed TTS are
summarized. An attempt has been made to synthesize the major findings across
experiments to provide the current state of knowledge for the effects of noise on
marine mammal hearing.
PMID- 26428809
TI - Benefits and applications of laser-induced sparks in real scale model
measurements.
AB - The characteristics of using a laser-induced spark as a monopole source in scale
model measurements were assessed by comparison with an electric spark and a
miniature spherical loudspeaker. Room impulse responses of first order
directivity sources were synthesized off-line using six spatially distributed
sparks. The source steering direction was scanned across the horizontal and
vertical plane to assess the origin of early reflections. The results confirm
that the characteristics of the laser-induced spark outperform those of typical
sources. Its monopole characteristics enable the authors to synthesize room
responses of directional sources, e.g., to obtain directional information about
reflections inside scale models.
PMID- 26428807
TI - Killer whale (Orcinus orca) whistles from the western South Atlantic Ocean
include high frequency signals.
AB - Acoustic parameters of killer whale (Orcinus orca) whistles were described for
the western South Atlantic Ocean and highlight the occurrence of high frequency
whistles. Killer whale signals were recorded on December of 2012, when a pod of
four individuals was observed harassing a group of sperm whales. The high
frequency whistles were highly stereotyped and were modulated mostly at
ultrasonic frequencies. Compared to other contour types, the high frequency
whistles are characterized by higher bandwidths, shorter durations, fewer
harmonics, and higher sweep rates. The results add to the knowledge of vocal
behavior of this species.
PMID- 26428810
TI - High sentence predictability increases the fluctuating masker benefit.
AB - This study examined the effects of sentence predictability and masker modulation
type on the fluctuating masker benefit (FMB), the improvement in speech reception
thresholds resulting from fluctuations imposed on a steady-state masker. Square
wave modulations resulted in a larger FMB than sinusoidal ones. FMBs were also
larger for high compared to low-predictability sentences, indicating that high
sentence predictability increases the benefits from glimpses of the target speech
in the dips of the fluctuating masker. In addition, sentence predictability
appears to have a greater effect on sentence intelligibility when the masker is
fluctuating than when it is steady-state.
PMID- 26428811
TI - Validation of a simple response-time measure of listening effort.
AB - This study compares two response-time measures of listening effort that can be
combined with a clinical speech test for a more comprehensive evaluation of total
listening experience; verbal response times to auditory stimuli (RT(aud)) and
response times to a visual task (RTs(vis)) in a dual-task paradigm. The listening
task was presented in five masker conditions; no noise, and two types of noise at
two fixed intelligibility levels. Both the RTs(aud) and RTs(vis) showed effects
of noise. However, only RTs(aud) showed an effect of intelligibility. Because of
its simplicity in implementation, RTs(aud) may be a useful effort measure for
clinical applications.
PMID- 26428812
TI - Methods to calibrate the absolute receive sensitivity of single-element, focused
transducers.
AB - Absolute pressure measurements of acoustic emissions by single-element, focused
passive cavitation detectors would be facilitated by improved wideband receive
calibration techniques. Here, calibration methods were developed to characterize
the absolute, frequency-dependent receive sensitivity of a spherically focused,
single-element transducer using pulse-echo and pitch-catch techniques. Validation
of these calibration methods on a focused receiver were made by generating a
pulse from a small diameter source at the focus of the transducer and comparing
the absolute pressure measured by a calibrated hydrophone to that of the focused
transducer using the receive sensitivities determined here.
PMID- 26428813
TI - Acquisition of speech rhythm in first language.
AB - Analysis of English rhythm in speech produced by children and adults revealed
that speech rhythm becomes increasingly more stress-timed as language acquisition
progresses. Children reach the adult-like target by 11 to 12 years. The employed
speech elicitation paradigm ensured that the sentences produced by adults and
children at different ages were comparable in terms of lexical content, segmental
composition, and phonotactic complexity. Detected differences between child and
adult rhythm and between rhythm in child speech at various ages cannot be
attributed to acquisition of phonotactic language features or vocabulary, and
indicate the development of language-specific phonetic timing in the course of
acquisition.
PMID- 26428814
TI - Across-frequency processing of modulation phase differences in hearing-impaired
listeners.
AB - Two experiments tested the influence of hearing impairment (HI) on representing
across-frequency temporal coherence. In one experiment, HI listeners demonstrated
similar abilities to normal-hearing listeners in detecting across-frequency
differences in modulation phase. In another, spectral-shape discrimination was
detrimentally affected by modulation phase disparities imposed on spectral
components. Spectral-shape discrimination by HI listeners was less influenced by
the disparities, suggesting that hearing loss alters the representation of
envelope phase. Results suggest that multiple approaches may be necessary to
determine alterations associated with hearing loss-detection tasks may not be
sufficient to elucidate distortions to temporal envelope associated with hearing
loss.
PMID- 26428815
TI - Relating movement recurrence and expressive timing patterns in music
performances.
AB - In this study the movement patterns of ten expert musicians are quantitatively
related to expressive timing patterns and the music structure during
performances. The hypothesis is that ancillary gestures recurrently employed are
closely related to expressive intentions, and that the expressive content imposed
in key musical passages is thus reflected in the patterns of gestural recurrence.
A movement and an audio analysis of 30 clarinet performances of a Brahms' excerpt
are compared. Results show direct correlations between the recurrence pattern of
clarinetists' ancillary movements and expressive bar duration manipulations
employed by them, associated with melodic phrasing and harmonic transitions.
PMID- 26428816
TI - Broadband sound blocking in phononic crystals with rotationally symmetric
inclusions.
AB - This paper investigates the feasibility of broadband sound blocking with
rotationally symmetric extensible inclusions introduced in phononic crystals. By
varying the size of four equally shaped inclusions gradually, the phononic
crystal experiences remarkable changes in its band-stop properties, such as
shifting/widening of multiple Bragg bandgaps and evolution to resonance gaps.
Necessary extensions of the inclusions to block sound effectively can be
determined for given incident frequencies by evaluating power transmission
characteristics. By arraying finite dissimilar unit cells, the resulting phononic
crystal exhibits broadband sound blocking from combinational effects of multiple
Bragg scattering and local resonances even with small-numbered cells.
PMID- 26428817
TI - Speaking rate consistency in native and non-native speakers of English.
AB - Non-native speech differs from native speech in multiple ways. Previous research
has described segmental and suprasegmental differences between native and non
native speech in terms of group averages. For example, average speaking rate for
non-natives is slower than for natives. However, it is unknown whether non-native
speech is also more variable than native speech. This study introduces a method
of comparing rate change across utterances, demonstrating that non-native
speaking rate is more variable than native speech. These results suggest that
future work examining non-native speech perception and production should
investigate both mean differences and variability in the signal.
PMID- 26428818
TI - Improved speech inversion using general regression neural network.
AB - The problem of nonlinear acoustic to articulatory inversion mapping is
investigated in the feature space using two models, the deep belief network (DBN)
which is the state-of-the-art, and the general regression neural network (GRNN).
The task is to estimate a set of articulatory features for improved speech
recognition. Experiments with MOCHA-TIMIT and MNGU0 databases reveal that, for
speech inversion, GRNN yields a lower root-mean-square error and a higher
correlation than DBN. It is also shown that conjunction of acoustic and GRNN
estimated articulatory features yields state-of-the-art accuracy in broad class
phonetic classification and phoneme recognition using less computational power.
PMID- 26428819
TI - An electronically tunable duct silencer using dielectric elastomer actuators.
AB - A duct silencer with tunable acoustic characteristics is presented in this paper.
Dielectric elastomer, a smart material with lightweight, high elastic energy
density and large deformation under high direct current/alternating current
voltages, was used to fabricate this duct silencer. The acoustic performances and
tunable mechanisms of this duct silencer were experimentally investigated. It was
found that all the resonance peaks of this duct silencer could be adjusted using
external control signals without any additional mechanical part. The physics of
the tunable mechanism is further discussed based on the electro-mechanical
interactions using finite element analysis. The present promising results also
provide insight into the appropriateness of the duct silencer for possible use as
next generation acoustic treatment device to replace the traditional acoustic
treatment.
PMID- 26428820
TI - A theoretical relation between the celerity and trace velocity of infrasonic
phases.
AB - This paper presents a relationship between the celerity and trace velocity of
infrasound signals propagating in a stratified, windy atmosphere. Despite their
importance, known celerity values have only been determined empirically. An
infrasonic phase (I-phase) diagram is developed which is useful in identifying
different I-phases. Such an I-phase diagram allows for the prediction of the
range of values of the celerity and trace velocity for each I-phase. The phase
diagram can easily be extended to underwater acoustic and acoustic-gravity waves.
An I-phase diagram is compared with data obtained from a ground-truth event where
qualitative agreement is obtained.
PMID- 26428821
TI - A model for the temporal evolution of the spatial coherence in decaying
reverberant sound fields.
AB - Reverberant sound fields are often modeled as isotropic. However, it has been
observed that spatial properties change during the decay of the sound field
energy, due to non-isotropic attenuation in non-ideal rooms. In this letter, a
model for the spatial coherence between two sensors in a decaying reverberant
sound field is developed for rectangular rooms. The modeled coherence function
depends on room dimensions, surface reflectivity, and orientation of the sensor
pair, but is independent of the position of source and sensors in the room. The
model includes the spherically isotropic (diffuse) and cylindrically isotropic
sound field models as special cases.
PMID- 26428822
TI - Subwavelength acoustic metamaterial panels for underwater noise isolation.
AB - Acoustically thin metamaterial underwater noise isolation panels have been
developed that provide as much as 16 dB of noise isolation for a panel with a
thickness just 160th of the wavelength in the host medium (fresh water) at 2.5
kHz. The panels are composed of thin layers of neoprene rubber and
polyoxymethylene containing air-filled voids. The level of isolation provided by
the panels is shown to correlate positively with the volume fraction of air voids
within the panel.
PMID- 26428823
TI - Distinct effects of moisture and air contents on acoustic properties of sandy
soil.
AB - Knowledge of distinct effects of moisture content and air volume on acoustic
properties of soil is sought to predict the influence of human activities such as
cultivation on acoustic propagation outdoors. This work used an impedance tube
with the two-thickness method to investigate such effects. For a constant
moisture weight percentage, the magnitude of the characteristic impedance became
smaller and the absorption coefficient became higher with increase of the air
space ratio. For a constant air space ratio, the absorption coefficient became
larger and the magnitude of the propagation constant became smaller with
increasing moisture weight percentage.
PMID- 26428824
TI - Uncertainty of decibel levels.
AB - The mean sound exposure level from a source is routinely estimated by the mean of
the observed sound exposures from repeated measurements. A formula for the
standard uncertainty based on the Guide to the expression of Uncertainty in
Measurement (GUM) is derived. An alternative formula is derived for the case
where the GUM method fails. The formulas are applied on several examples, and
compared with a Monte Carlo calculation of the standard uncertainty. The
recommended formula can be seen simply as a convenient translation of the
uncertainty on an energy scale into the decibel level scale, but with a
theoretical foundation.
PMID- 26428825
TI - A biomimetic coupled circuit based microphone array for sound source
localization.
AB - An equivalent analog circuit is designed to mimic the coupled ears of the fly
Ormia ochracea for sound source localization. This coupled circuit receives two
signals with tiny phase difference from a space closed two-microphone array, and
produces two signals with obvious intensity difference. The response sensitivity
can be adjusted through the coupled circuit parameters. The directional
characteristics of the coupled circuit have been demonstrated in the experiment.
The miniature microphone array can localize the sound source with low
computational burden by using the intensity difference. This system has
significant advantages in various applications where the array size is limited.
PMID- 26428826
TI - Echolocation of insects using intermittent frequency-modulated sounds.
AB - Using echolocation influenced by Doppler shift, bats can capture flying insects
in real three-dimensional space. On the basis of this principle, a model that
estimates object locations using frequency modulated (FM) sound was proposed.
However, no investigation was conducted to verify whether the model can localize
flying insects from their echoes. This study applied the model to estimate the
range and direction of flying insects by extracting temporal changes from the
time-frequency pattern and interaural range difference, respectively. The results
obtained confirm that a living insect's position can be estimated using this
model with echoes measured while emitting intermittent FM sounds.
PMID- 26428827
TI - Parameterization of the three-dimensional room transfer function in horizontal
plane.
AB - This letter proposes an efficient parameterization of the three-dimensional room
transfer function (RTF) which is robust for the position variations of source and
receiver in respective horizontal planes. Based on azimuth harmonic analysis, the
proposed method exploits the underlying properties of the associated Legendre
functions to remove a portion of the spherical harmonic coefficients of RTF which
have no contribution in the horizontal plane. This reduction leads to a flexible
measuring-point structure consisting of practical concentric circular arrays to
extract horizontal plane RTF coefficients. The accuracy of the above
parameterization is verified through numerical simulations.
PMID- 26428828
TI - Empirical estimation of peak pressure level from sound exposure level. Part II:
Offshore impact pile driving noise.
AB - Numerical models of underwater sound propagation predict the energy of impulsive
signals and its decay with range with a better accuracy than the peak pressure. A
semi-empirical formula is suggested to predict the peak pressure of man-made
impulsive signals based on numerical predictions of their energy. The approach
discussed by Galindo-Romero, Lippert, and Gavrilov [J. Acoust. Soc. Am. 138, in
press (2015)] for airgun signals is modified to predict the peak pressure from
offshore pile driving, which accounts for impact and pile parameters. It is shown
that using the modified empirical formula provides more accurate predictions of
the peak pressure than direct numerical simulations of the signal waveform.
PMID- 26428829
TI - Forward scattering detection of a submerged moving target based on adaptive
filtering technique.
AB - Forward scattered waves are always overwhelmed by severely intense direct blasts
when a submerged target crosses the source-receiver line. A processing scheme
called direct blast suppression based on adaptive filtering (DBS-AF) is proposed
to suppress such blasts. A verification experiment was conducted in a lake with a
vertical hydrophone array and 10 kHz CW impulses. Processing results show that
the direct blast is suppressed in a single channel, and an intruding target is
identified by the lobes in the detection curve. The detection performance is
improved by adopting a time-delay beam-former on the array as a pre-processing
technique.
PMID- 26428830
TI - Passive acoustic observations of tide height in the Iroise Sea using ambient
noise.
AB - Considering a broadband motionless source in a waveguide with a depth that varies
with time, the time-frequency representation of the acoustic intensity shows a
striation pattern than can be explained using the depth-frequency waveguide
invariant. This phenomenon is used here to describe acoustic data recorded in the
Iroise Sea, where intense tides occur. The originality of this study is that the
acoustic data consist of only ambient noise. The best hypothesis is that these
striations are created by distant marine traffic in the Bay of Brest, and the
results suggest that tide height can be monitored using long-term passive
acoustics.
PMID- 26428831
TI - Outdoor measurements of spherical acoustic shock decay.
AB - Prior anechoic measurements of a small acetylene-oxygen balloon explosion were
used to study spherical weak-shock decay over short ranges [Muhlestein et al., J.
Acoust. Soc. Am. 131, 2422-2430 (2012)]. Here, longer-range measurements
conducted at the Bonneville Salt Flats with a larger balloon are described.
Waveform and spectral characteristics and comparisons of the peak pressure decay
with an analytical weak-shock model are presented. Weak shocks persist to at
least 305 m, with an amplitude decay that is predicted reasonably well using the
model. Deviations are discussed in the context of atmospheric effects and
nonlinear ground reflections.
PMID- 26428833
TI - Spectral density affects the intelligibility of tone-vocoded speech: Implications
for cochlear implant simulations.
AB - For small numbers of channels, tone vocoders using low envelope cutoff
frequencies are less intelligible than noise vocoders, even though the noise
carriers introduce random fluctuations into the crucial envelope information.
Here it is shown that using tone carriers with a denser spectrum improves
performance considerably over typical tone vocoders, at least equaling, and often
surpassing, the performance possible with noise vocoders. In short, the spectral
sparseness of tone vocoded sounds for low channel numbers, separate from the
degradations introduced by using only a small number of channels, is an important
limitation on the intelligibility of tone-vocoded speech.
PMID- 26428832
TI - Toddlers' comprehension of degraded signals: Noise-vocoded versus sine-wave
analogs.
AB - Recent findings suggest that development changes the ability to comprehend
degraded speech. Preschool children showed greater difficulties perceiving noise
vocoded speech (a signal that integrates amplitude over broad frequency bands)
than sine-wave speech (which maintains the spectral peaks without the spectrum
envelope). In contrast, 27-month-old children in the present study could
recognize speech with either type of degradation and performed slightly better
with eight-channel vocoded speech than with sine-wave speech. This suggests that
children's identification performance depends critically on the degree of
degradation and that their success in recognizing unfamiliar speech encodings is
encouraging overall.
PMID- 26428834
TI - Influence of language experience on digit recognition by English and Chinese
listeners.
AB - Digit recognition was measured in quiet and in two noise conditions by English
native (EN) and Chinese-native (CN) listeners. EN listeners were tested using
English digits and CN listeners were tested using both English and Chinese
digits. In quiet, forward digit span recall worsened for both groups as the
number of digits was increased. Significant effects of language experience were
observed with five or more digits. Language experience had a significant effect
on digit recognition in babble but not in steady noise. These results suggest
that understanding of a nonnative language can be influenced by both cognitive
load and listening environment.
PMID- 26428835
TI - Cross-coherent vector sensor processing for spatially distributed glider
networks.
AB - Autonomous underwater gliders fitted with vector sensors can be used as a
spatially distributed sensor array to passively locate underwater sources.
However, to date, the positional accuracy required for robust array processing
(especially coherent processing) is not achievable using dead-reckoning while the
gliders remain submerged. To obtain such accuracy, the gliders can be temporarily
surfaced to allow for global positioning system contact, but the acoustically
active sea surface introduces locally additional sensor noise. This letter
demonstrates that cross-coherent array processing, which inherently mitigates the
effects of local noise, outperforms traditional incoherent processing source
localization methods for this spatially distributed vector sensor network.
PMID- 26428836
TI - Ultrasonic guided waves in elliptical annular cylinders.
AB - This paper studies the influence of cross-section ovalness or ellipticity on
lower order axisymmetric guided wave modes in thin pipes. The second longitudinal
mode L(0,2) and the fundamental torsional mode T(0,1) are studied, as these are
of interest to current pipe inspection. The semi-analytical finite element (FE)
method is mainly used, with three-dimensional FE simulations for visualization
and cross-validation of results. The studies reveal that even a small degree of
ovalness can affect mode shapes and velocities. The effect is more pronounced on
the L(0,2) mode than on T(0,1) and this may be important for practical inspection
applications.
PMID- 26428837
TI - Sternal vibrations during head-out immersion: A preliminary demonstration of
underwater wearable ballistocardiography.
AB - Ballistocardiography (BCG) measures vibrations of the body caused by ejection of
blood from the heart, and the root mean square (RMS) of BCG measured with a
weighing scale trends with cardiac output. However, BCG underwater has not been
studied. Head-to-foot BCG signals were recorded with an accelerometer on the
sternum of three human subjects. The heartbeats were clearly visible in the
signals recorded underwater, and the resting change in RMS BCG was +360 MUg
(+36%) from air to cold water immersion (27.8 degrees C) while standing. This is
within the 32%-62% increase in cardiac output observed in previous head-out
immersion studies.
PMID- 26428838
TI - Melodic contour identification and sentence recognition using sung speech.
AB - For bimodal cochlear implant users, acoustic and electric hearing has been shown
to contribute differently to speech and music perception. However, differences in
test paradigms and stimuli in speech and music testing can make it difficult to
assess the relative contributions of each device. To address these concerns, the
Sung Speech Corpus (SSC) was created. The SSC contains 50 monosyllable words sung
over an octave range and can be used to test both speech and music perception
using the same stimuli. Here SSC data are presented with normal hearing listeners
and any advantage of musicianship is examined.
PMID- 26428839
TI - Modified spectral tilt affects infants' native-language discrimination of
approximants and vowels.
AB - This study's aim was to determine if 6- and 9-month-old infants discriminate
approximants and vowels when the spectral shape is modified to emphasize high- or
low-frequency information. Infants were presented with /r/-/l/ and /o/-/a/ in
three conditions: (a) unmodified; (b) -6 dB/octave tilt; and (c) +6 dB/octave
tilt. Six-month-olds discriminated /o/-/a/ in conditions (a) and (b), and /r/-/l/
in conditions (a) and (c), but 9-month-olds only discriminated when unmodified.
The results reflect native-language attunement. Six-month-olds discriminate
spectrally modified sounds that emphasize relevant cues, but by 9 months, infants
are sensitive to the native spectral profiles of speech.
PMID- 26428840
TI - Response to Letter to the Editor regarding "Systematic review of
flexion/extension radiography of the cervical spine in trauma patients".
PMID- 26428841
TI - Pilot study of ultrasound parotid imaging reporting and data system (PIRADS):
Inter-observer agreement.
AB - AIM: To establish proposal ultrasound parotid imaging reporting and data system
(PIRADS) for classification and prediction of malignancy of parotid lesions and
to assess the inter-observer agreement of this system. SUBJECTS AND METHODS:
Retrospective analysis of ultrasound and power Duplex images of 142 patients with
parotid lesions by two reviewers. Parotid focal lesions were classified into nine
patterns and then categorized into five groups: PIRADS 1, definitively benign;
PIRADS 2, probably benign; PIRADS 3, indeterminate; PIRADS 4, probably malignant;
and PIRADS 5, highly suggestive malignant. THE RESULTS: There was excellent
interobserver agreement of both reviewers for patterns and PIRADS (K=0.84,
P=0.001) with 92% percent agreement. There was excellent agreement of PIRADS 1
(K=1.00, P=0.001), PIRADS 2 (K=0.97, P=0.001), PIRADS 3 (K=0.86, P=0.001) and
PIRADS 5 (K=0.88, P=0.001) and good agreement of PIRADS 4 (K=0.67, P=0.001). The
Odds ratio of PIRADS 3, 4 and 5 were 1.36 (95% CI=0.39-4.55), 7.11 (95% CI=3.02
11.15) and 8.27 (95% CI=3.49-10.27) respectively. The accuracy was 92% and 90%,
sensitivity was 79% and 65%, specificity was 94% and 96% of PIRADS of both
reviewers respectively. CONCLUSION: The proposed PIRADS is a reliable non
invasive imaging modality that can be used for categorizing parotid lesions and
prediction of malignancy.
PMID- 26428842
TI - Volume perfusion computed tomography (VPCT)-based evaluation of response to TACE
using two different sized drug eluting beads in patients with nonresectable
hepatocellular carcinoma: Impact on tumor and liver parenchymal vascularisation.
AB - OBJECTIVE: Response monitoring of transarterial chemoembolization (TACE) with the
help of volume perfusion computed tomography (VPCT) at day one post-TACE and
analysis of TACE-impact on tumor and uninvolved liver parenchymal perfusion by
using different particles sizes and epirubicin dose. MATERIALS AND METHODS:
Institutional review board approved this prospective study. VPCT was performed in
the baseline, post-interventional (FU1; 24 h post-TACE) and at follow-up (FU2;
median, 81 days) in 45 consecutive patients. 100-300 MUm (n=17) and 300-500 MUm
(n=28) drug eluting beads (DEB) using an epirubicin dose of (<=25 vs. >25) were
administered. VPCT was performed for 40-s using 80 kV, 100/120 mAs, 64*0.6 mm
collimation, 26 consecutive measurements, IV injection (50 ml iodinated
contrast), flow rate (5 ml/s). Blood flow (BF), blood volume (BV) and k-trans
were registered as average and max values in the tumor. Arterial liver perfusion
(ALP), portal-venous perfusion (PVP) and the hepatic perfusion index (HPI) were
registered both in tumor and non-involved liver parenchyma. Response to TACE was
classified by VPCT as complete (CR), partial (PR) or no response (NR). RESULTS: A
significant reduction of viable tumor tissue was found in all patients between
baseline and FU1 (p<0.001) being independent on particle size and epirubicin dose
(p>0.05). PPV/NPV/sensitivity/specificity of post-interventional VPCT (FU1)
results for prediction of the mid-term tumor course (FU2) were 100%/70%/76%/100%.
There was generally a significant increase of the ALP between baseline and FU1 in
the liver parenchyma coupled by a significant subsequent decrease (normalization)
of ALP and HPI between FU1 and FU2. CONCLUSION: VPCT accurately measures impact
of TACE on liver tumor and hepatic parenchymal perfusion. The former proved not
to be significantly dependent on particle size and epirubicin dose. There was no
persistent perfusion deficit in the liver after TACE.
PMID- 26428844
TI - Importance of recognizing sleep health disparities and implementing innovative
interventions to reduce these disparities.
PMID- 26428843
TI - Disparities and genetic risk factors in obstructive sleep apnea.
AB - Obstructive sleep apnea (OSA) is an increasingly prevalent condition. A growing
body of literature supports substantial racial disparities in the prevalence,
risk factors, presentation, diagnosis, and treatment of this disease.
Craniofacial structure among Asians appears to confer an elevated risk of OSA
despite lower rates of obesity. Among African Americans, Native Americans, and
Hispanics, OSA prevalence is increased, likely due in part to obesity. The burden
of symptoms, particularly excessive daytime sleepiness, is higher among African
Americans, although Hispanics more often report snoring. Limited data suggest
that African Americans may be more susceptible to hypertension in the setting of
OSA. While differences in genetic risk factors may explain disparities in OSA
burden, no definitive genetic differences have yet been identified. In addition
to disparities in OSA development, disparities in OSA diagnosis and treatment
have also been identified. Increased severity of disease at diagnosis among
African Americans suggests a delay in diagnosis. Treatment outcomes are also
suboptimal among African Americans. In children, tonsillectomy is less likely to
cure OSA and more commonly associated with complications in this group. Among
adults, adherence to continuous positive airway pressure (CPAP) is substantially
lower in African Americans. The reasons for these disparities, particularly in
outcomes, are not well understood and should be a research priority.
PMID- 26428846
TI - Incidence and predisposing factors for the development of disturbed glucose
metabolism and DIabetes mellitus AFter Intensive Care admission: the DIAFIC
study.
AB - INTRODUCTION: Elevated blood glucose levels during intensive care unit (ICU)
stay, so-called stress hyperglycaemia (SH), is a common finding. Its relation
with a future diabetes risk is unclear. Our objective was to determine the
incidence of disturbed glucose metabolism (DGM) post ICU admission and to
identify predictors for future diabetes risk with a focus on stress
hyperglycaemia. METHODS: This single center prospective cohort trial (DIAFIC
trial) had a study period between September 2011 and March 2013, with follow-up
until December 2013. The setting was a mixed medical/surgical ICU in a tertiary
teaching hospital in Belgium. 338 patients without known diabetes mellitus were
included for analysis. We assessed the level of glucose metabolism disturbance
(as diagnosed with a 75 g oral glucose tolerance test (OGTT) and/or HbA1c level)
eight months after ICU admission, and investigated possible predictors including
stress hyperglycaemia. RESULTS: In total 246 patients (73 %) experienced stress
hyperglycaemia during the ICU stay. Eight months post-ICU admission, 119 (35 %)
subjects had a disturbed glucose metabolism, including 24 (7 %) patients who were
diagnosed with diabetes mellitus. A disturbed glucose metabolism tended to be
more prevalent in subjects who experienced stress hyperglycaemia during ICU stay
as compared to those without stress hyperglycaemia (38 % vs. 28 %, P = 0.065).
HbA1c on admission correlated with the degree of stress hyperglycaemia. A
diabetes risk score (FINDRISC) (11.0 versus 9.5, P = 0.001), the SAPS3 score
(median of 42 in both groups, P = 0.003) and daily caloric intake during ICU stay
(197 vs. 222, P = 0.011) were independently associated with a disturbed glucose
metabolism. CONCLUSIONS: Stress hyperglycaemia is frequent in non-diabetic
patients and predicts a tendency towards disturbances in glucose metabolism and
diabetes mellitus. Clinically relevant predictors of elevated risk included a
high FINDRISC score and a high SAPS3 score. These predictors can provide an
efficient, quick and inexpensive way to identify patients at risk for a disturbed
glucose metabolism or diabetes, and could facilitate prevention and early
treatment. TRIAL REGISTRATION: At ClinicalTrials.gov NCT02180555 . Registered 1
July, 2014.
PMID- 26428847
TI - Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and
Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung
adenocarcinoma.
AB - T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been
shown to play an important role in mediating NK-cell function in human diseases.
However, the relationship between Tim-3 expression in natural killer (NK) cells
and human lung adenocarcinoma remains unclear. We therefore investigated the
expression of Tim-3 in NK cells and explored the effect of Tim-3 blockade on NK
cell-mediated activity in human lung adenocarcinoma. Upregulated expression of
Tim-3 on CD3-CD56+ cells (P<0.05) and CD3-CD56(dim) cells (P<0.05) of patients
with lung adenocarcinoma was detected by flow cytometry. Moreover, Tim-3
expression in CD3-CD56+ NK cells was higher in patients with lung adenocarcinoma
with lymph node metastasis (LNM) (P<0.05) or with tumor stage T3-T4 (P<0.05). Tim
3 expression in CD56(dim) NK-cell subset was higher in patients with tumor size
>=3cm (P<0.05), or LNM (P<0.05) or with tumor stage T3-T4 (P<0.05). Further
analysis showed that higher expressions of Tim-3 on both CD3-CD56+ NK cells and
CD56(dim) NK-cell subset were independently correlated with shorter overall
survival of patients with lung adenocarcinoma (log-rank test, P=0.0418, 0.0406,
respectively). Importantly, blockade of Tim-3 signaling with anti-Tim-3
antibodies resulted in the increased cytotoxicity and IFN-gamma production of
peripheral NK cells from patients with lung adenocarcinoma. Our data indicate
that Tim-3 expression in NK cells can function as a prognostic biomarker in human
lung adenocarcinoma and support that Tim-3 could be a new target for an
immunotherapeutic strategy.
PMID- 26428845
TI - Cellular Therapies in Trauma and Critical Care Medicine: Forging New Frontiers.
AB - Trauma is a leading cause of death in both military and civilian populations
worldwide. Although medical advances have improved the overall morbidity and
mortality often associated with trauma, additional research and innovative
advancements in therapeutic interventions are needed to optimize patient
outcomes. Cell-based therapies present a novel opportunity to improve trauma and
critical care at both the acute and chronic phases that often follow injury.
Although this field is still in its infancy, animal and human studies suggest
that stem cells may hold great promise for the treatment of brain and spinal cord
injuries, organ injuries, and extremity injuries such as those caused by
orthopedic trauma, burns, and critical limb ischemia. However, barriers in the
translation of cell therapies that include regulatory obstacles, challenges in
manufacturing and clinical trial design, and a lack of funding are critical areas
in need of development. In 2015, the Department of Defense Combat Casualty Care
Research Program held a joint military-civilian meeting as part of its effort to
inform the research community about this field and allow for effective planning
and programmatic decisions regarding research and development. The objective of
this article is to provide a "state of the science" review regarding cellular
therapies in trauma and critical care, and to provide a foundation from which the
potential of this emerging field can be harnessed to mitigate outcomes in
critically ill trauma patients.
PMID- 26428848
TI - Anti-inflammatory activities of phospholipase C inhibitor U73122: Inhibition of
monocyte-to-macrophage transformation and LPS-induced pro-inflammatory cytokine
expression.
AB - A wide range of biological processes are controlled by phospholipase C
(PLC)/Ca(2+) signaling, which could be blocked by PLC-specific inhibitor U73122.
Whether inhibition of PLC with chemical inhibitor U73122 affects the inflammatory
response in monocytes/macrophages is currently unknown. In this study, we
demonstrated that U73122 inhibited PMA-induced in vitro differentiation of human
promonocytic U937 cells into macrophages as reflected by the reduction of cell
adherence and the decreased expression of macrophage specific marker CD163. It is
possible that U73122 blocked PMA-induced adhesion of U937 cells partially by down
regulation and inactivation of both Pyk2 and paxillin signaling. Furthermore, the
expression of LPS-induced pro-inflammatory cytokines TNF-alpha and IL-1beta was
significantly blocked by U73122 in both dU937 cells and mouse primary peritoneal
macrophages. These results suggest that PLC is involved in the sophisticated
inflammatory response by monocytes/macrophages, and thereby chemical antagonists
of PLC may be potential agents for the suppression of inflammatory response.
PMID- 26428849
TI - Inhibitory effect of brazilin on osteoclast differentiation and its mechanism of
action.
AB - Brazilin isolated from Caesalpinia sappan has long been known as a natural red
pigment. Our study evaluated the inhibitory effect of brazilin on osteoclast
differentiation and investigated its mechanism of action. Our results
demonstrated that brazilin inhibited receptor activator of nuclear factor kappa-B
ligand (RANKL)-mediated osteoclast differentiation in RAW264.7 cells in a dose
dependent manner, without any evidence of cytotoxicity. The mRNA expression of
tartrate-resistant acid phosphatase (TRAP), nuclear factor of activated T-cells,
cytoplasmic 1 (NFATc1), matrix metalloproteinase 9 (MMP-9), and cathepsin K in
RANKL-treated RAW264.7 cells was inhibited by brazilin treatment. Brazilin also
decreased RANKL-induced expression of inflammatory mediator genes such as
inducible nitric oxide synthase, iNOS; cyclooxygenase (COX)-2, tumor necrosis
factor (TNF)-alpha, and interleukin (IL)-6 and inhibited extracellular signal
regulated kinases (ERK) and nuclear factor kappa-light-chain-enhancer of
activated B cell (NF-kappaB) p65 phosphorylation in RANKL-stimulated RAW264.7
cells. A lipopolysaccharide (LPS)-induced osteoporosis study was also performed
to assess the effects of brazilin in vivo. Micro-computed tomography (CT)
analysis of the femurs showed that LPS treatment causes bone loss in mice, but it
was significantly attenuated after co-treatment with brazilin (100mg/kg).
Therefore, brazilin may have therapeutic potential in preventing bone loss.
PMID- 26428850
TI - Intravenous immunoglobulin treatment in a HIV-1 positive patient with Guillain
Barre syndrome.
AB - We report the case of an HIV-1 positive patient with primary demyelinating
neuropathy (Guillain-Barre syndrome); after intravenous immunoglobulin treatment
(IVIG), he presented with an increase in CD4 and CD8 cell counts and a decrease
in plasma viral load. Currently, there is little reported research regarding IVIG
treatment in adults with HIV-1. The present report brings further evidence
regarding the possible benefit of IVIG in HIV-1 infected patients, providing a
novel perspective on treatment.
PMID- 26428851
TI - HSPA12B attenuates acute lung injury during endotoxemia in mice.
AB - Acute lung injury (ALI) is a critical manifestation of sepsis/septic shock. Heat
shock protein A12B (HSPA12B), an endothelial cell-expressed heat shock protein,
shows a negative regulation of lipopolysaccharide (LPS)-induced inflammation in
myocardium and endothelial cells. However, it is unclear whether HSPA12B exerts
protective effects against ALI during sepsis/septic shock. In this study, we
treated HSPA12B transgenic mice (Tg) and wild type littermates (WT) with LPS for
6h to induce endotoxemia. LPS treatment significantly caused pulmonary injuries
as evidenced by microarchitecture destruction, vascular leakage and neutrophil
recruitment in lungs of WT mice. However, the LPS-induced pulmonary injuries were
significantly attenuated in Tg mice. Moreover, the LPS-induced activation of
extracellular signal-regulated kinases (ERKs) and upregulation of intercellular
adhesion molecule-1 (ICAM-1) and Cyclooxygenase-2 (Cox-2) were inhibited in Tg
lungs compared with that in WT mice. Additionally, Tg lungs showed a significant
lower level of vascular endothelial growth factor (VEGF) compared with WT mice.
Our results demonstrate a pulmonary protective effect of HSPA12B against
endotoxin challenge, which indicates management of HSPA12B expression could serve
as a potential therapeutic target for ALI during sepsis/septic shock.
PMID- 26428852
TI - The design and initial patient evaluation of an integrated care pathway for
faecal incontinence: a qualitative study.
AB - BACKGROUND: Faecal incontinence is a common, distressing and debilitating
condition which remains largely hidden, leading to social isolation and loss of
confidence. Patients with faecal incontinence experience delays in accessing
appropriate treatment services due to embarrassment and lack of enquiry from
primary care health professionals. Despite the publication of three government
documents related to continence services in the last decade, these services are
still fragmented with asynchronous delivery and poor inter-professional
integration. The aim of the study was to describe a novel integrated care pathway
for the management of faecal incontinence and examine the experiences of patients
with faecal incontinence in relation to this pathway. METHODS: A focus group
(eight participants) and narrative, qualitative individual interviews (five
participants) were used to explore the views of patients with faecal
incontinence, relating to access and quality of incontinence services and the new
integrated care pathway. Emerging themes were identified from the transcribed
focus group and interviews via the thematic analysis method. RESULTS: The concept
of an integrated care pathway is attractive for increasing accessibility,
streamlining of the patient pathway and providing a dedicated service for the
management of faecal incontinence. Patients' initial experiences of the pathway
are positive. DISCUSSION: A new ICP was developed and the initial patient
evaluation of it was positive. Service users made various suggestions how the FI
pathway could have been improved. The issues that patients were most concerned
about were access to continence services, GP awareness of continence services and
prompt, effective management of their condition. This service was set up within
the pelvic floor dysfunction unit with BFNS and an integrated community
continence team. The authors are aware that this is not a standard service setup
across the country. The fact that it may be uncomfortable for patients to talk
about their condition may have led to potential bias when discussing their
beliefs or experiences. As with most qualitative studies, our aim was to identify
a range of experiences rather than define our participant sample as being
representative. Our participant sample was diverse in the key characteristics but
a longitudinal study may reveal further important aspects of an ICP for FI.
CONCLUSIONS: An integrated care pathway for faecal incontinence appears to have
potential to address the long-standing service delivery issues that have blighted
continence services historically.
PMID- 26428853
TI - Genome-wide analysis of tandem repeats in Tribolium castaneum genome reveals
abundant and highly dynamic tandem repeat families with satellite DNA features in
euchromatic chromosomal arms.
AB - Although satellite DNAs are well-explored components of heterochromatin and
centromeres, little is known about emergence, dispersal and possible impact of
comparably structured tandem repeats (TRs) on the genome-wide scale. Our
bioinformatics analysis of assembled Tribolium castaneum genome disclosed
significant contribution of TRs in euchromatic chromosomal arms and clear
predominance of satellite DNA-typical 170 bp monomers in arrays of >=5 repeats.
By applying different experimental approaches, we revealed that the nine most
prominent TR families Cast1-Cast9 extracted from the assembly comprise ~4.3% of
the entire genome and reside almost exclusively in euchromatic regions. Among
them, seven families that build ~3.9% of the genome are based on ~170 and ~340 bp
long monomers. Results of phylogenetic analyses of 2500 monomers originating from
these families show high-sequence dynamics, evident by extensive exchanges
between arrays on non-homologous chromosomes. In addition, our analysis shows
that concerted evolution acts more efficiently on longer than on shorter arrays.
Efficient genome-wide distribution of nine TR families implies the role of
transposition only in expansion of the most dispersed family, and involvement of
other mechanisms is anticipated. Despite similarities in sequence features, FISH
experiments indicate high-level compartmentalization of centromeric and
euchromatic tandem repeats.
PMID- 26428855
TI - Coxiella-like endosymbiont associated to the "Anatolian brown tick" Rhipicephalus
bursa in Southern Italy.
AB - Several different ticks have been reported to harbor microbes related to Coxiella
burnetii, the agent of the Q fever. Rhipicephalus bursa is an important vector of
tick-borne diseases in livestock in Mediterranean area; it is also abundant in
ovi-caprine farms with C. burnetii infection, in Southern Italy. 60 females of
Rh. bursa (15 pools) and 40 their eggs (2 pools) were screened for C. burnetii by
a conventional PCR targeting the insertion sequence IS1111 and by Loop mediated
isothermal amplification assay (LAMP) targeting com1 gene. One of 15 tick pools
(1/15) and both egg pools (2/2) were found positive by LAMP assay and negative by
PCR targeting IS1111 gene. 16S rRNA gene was amplified by PCR from the LAMP
positive pools, amplicons were sequenced and found 95% similar to the
corresponding sequences from C. burnetii. This let us to hypothesize the presence
of a new Coxiella-like endosymbiont associated with Rh. bursa which could be
vertically transmitted, described here for the first time. The lack of detection
of IS1111 in Coxiella endosymbiont of Rh. bursa could be related to the possible
absence of the Pathogenicity island of C. burnetii, to which IS1111s are
associated.
PMID- 26428856
TI - Waddlia chondrophila and Chlamydia trachomatis antibodies in screening infertile
women for tubal pathology.
AB - Since Waddlia chondrophila is closely related to Chlamydia trachomatis, we
hypothesise that W. chondrophila may also be associated with tubal factor
infertility (TFI) in women, a major complication of chronic C. trachomatis
infection. Five hundred twenty serum samples were tested for anti-Waddlia
antibodies by ELISA. Among the 520 investigated women, a total number of 142
(27.3%) has had laparoscopic diagnosis performed, and were either classified TFI
positive or negative. Presence of high titres of W. chondrophila antibodies was
linked to TFI (p < 0.0001; OR: 7.5; 95% CI: 3.3-17). Moreover, antibody
positivity to both W. chondrophila and C. trachomatis-MOMP was strongly
associated with TFI (p < 0.0001; OR: 21; 95% CI: 3.8-12E1). This association was
much stronger than the statistical association of C. trachomatis-MOMP antibodies
only (p < 0.0001; OR: 7.1; 95% CI: 3.7-14), suggesting that co-infection with W.
chondrophila and C. trachomatis may lead to more severe reproductive sequelae and
immune responses than single infection with either Chlamydiales members.
PMID- 26428858
TI - Nuclear Magnetic Resonance (NMR) as a tool for the study of the metabolism of
Rickettsia slovaca.
AB - Rickettsial infections are caused by intracellular bacteria. They do not grow in
standard culture media so there are limitations in routine practice to study
their metabolism. Nuclear Magnetic Resonance (NMR) spectroscopy is used for
identification of metabolites in biological samples. Vero cells infected with
Rickettsia slovaca as well as uninfected cells were monitored by (1)H NMR showing
the presence of ethanol and lactic acid. As no differences were observed, labeled
compounds were added into cultures. When D-[1-13C]glucose was monitored by (13)C
NMR no differences among infected and uninfected cells were observed in metabolic
profiles. Glucose was transformed into ethanol in all cultures. Monitored
experiments carried out with [2-13C]glycine showed differences between infected
and uninfected cell cultures spectra. Glycine was partially transformed into
serine, but the amount of the serine formed was larger in those infected.
Moreover, L-[2-13C]leucine, L-[1-13C]isoleucine and L-[15N]tyrosine were
evaluated. No differences among infected and uninfected cells were observed in
the metabolic profiles when tyrosine and leucine were monitored. The amino acid L
[1-13C]isoleucine exhibited different metabolism in presence of the R. slovaca,
showing a promising behavior as biomarker. In this work we focused on finding one
or more compounds that could be metabolized specifically by R. slovaca and could
be used as an indicator of its activity.
PMID- 26428857
TI - Anaplasma phagocytophilum infection in moose (Alces alces) in Norway.
AB - Anaplasma phagocytophilum is a tick-borne bacterium that infects a wide range of
animal species. The aim of our study was to investigate the prevalence of A.
phagocytophilum in Norwegian moose Alces alces and to characterize the bacteria
by sequencing of partial msp4 and 16S rRNA genes. Hunters collected spleen
samples from 99 moose of different ages during 2013 and 2014 in two areas: Aust
Agder County (n = 70) where Ixodes ricinus ticks are abundant and Oppland County
(n = 29) where ticks were either absent, or abundance very low. A.
phagocytophilum was detected only in moose from the I. ricinus - abundant area.
The overall prevalence of infection according to 16S rRNA and msp4 gene-based PCR
was 41.4% and 31.4% respectively. Sequence analysis of the partial 16S rRNA and
msp4 gene revealed two and eight different sequence types respectively. Four of
eight msp4 sequence types determined in this study were unique, while others were
identical to sequences derived from other ruminants and ticks. The present study
indicates that moose could be a potential wildlife reservoir of A.
phagocytophilum in Norway.
PMID- 26428859
TI - Isolation and maintenance of Rickettsia raoultii in a Rhipicephalus sanguineus
tick cell line.
AB - Rickettsia raoultii, a member of the spotted fever group rickettsiae, has been
implicated in cases of DEBONEL/TIBOLA/SENLAT, and has been detected in
Dermacentor spp. and Rhipicephalus pumilio ticks by PCR. R. raoultii has been
isolated in mammalian and tick cell lines. This study aimed to isolate R.
raoultii from Spanish Dermacentor marginatus in tick cell lines. A single adult
D. marginatus collected from vegetation in La Rioja (Northen Spain) in October
2012 was surface-sterilised, triturated and aliquots of the homogenate were
inoculated into a panel of tick cell lines derived from embryonic Rhipicephalus
sanguineus, Rhipicephalus evertsi and Ixodes ricinus. Cultures were maintained at
28 degrees C with weekly medium changes and checked by Gimenez stain for
Rickettsia-like intracellular organisms. After 50 days of incubation,
intracellular Rickettsia-like organisms were observed in the R. sanguineus cell
line RML-RSE using Gimenez stain. PCR assays and sequencing of fragments of 16S
RNA, ompB and ompA genes in DNA extracted from the culture suspension showed 100%
identity with R. raoultii. Growth of intracellular microorganisms was not
observed in preparations of the other tick cell lines. In conclusion, the tick
cell line RML-RSE is a useful system for the isolation and maintenance of R.
raoultii.
PMID- 26428860
TI - Up-regulation of Hsp72 and keratin16 mediates wound healing in streptozotocin
diabetic rats.
AB - BACKGROUND: Impaired wound healing is a complication of diabetes and a serious
problem in clinical practice. We previously found that whey protein (WP) was able
to regulate wound healing normally in streptozotocin (STZ)-diabetic models. This
subsequent study was designed to assess the effect of WP on heat shock protein-72
(Hsp72) and keratin16 (Krt16) expression during wound healing in diabetic rats.
METHODS: WP at a dosage of 100 mg/kg of body weight was orally administered daily
to wounded normal and STZ-diabetic rats for 8 days. RESULTS: At day 4, the WP
treated diabetic wound was significantly reduced compared to that in the
corresponding control. Diabetic wounded rats developed severe inflammatory
infiltration and moderate capillary dilatation and regeneration. Treated rats had
mild necrotic formation, moderate infiltration, moderate to severe capillary
dilatation and regeneration, in addition to moderate epidermal formation. Hsp72
and Krt16 densities showed low and dense activity in diabetic wounded and
diabetic wounded treated groups, respectively. At day 8, WP-treatment of diabetic
wounded animals revealed great amelioration with complete recovery and closure of
the wound. Reactivity of Hsp72 and Krt16 was reversed, showing dense and low, or
medium and low, activity in the diabetic wounded and diabetic wounded treated
groups, respectively. Hsp72 expression in the pancreas was found to show dense
reactivity with WP-treated diabetic wound rats. CONCLUSION: This data provides
evidence for the potential impact of WP in the up-regulation of Hsp72 and Krt16
in T1D, resulting in an improved wound healing process in diabetic models.
PMID- 26428862
TI - Sensory impact of lowering sugar content in orange nectars to design healthier,
low-sugar industrialized beverages.
AB - The presence of added sugars (AS) in the diet is associated with increased risk
of obesity and other chronic diseases. We assessed sensory impact of lowering AS
in orange nectar, aiming at new WHO sugar guideline. Ideal sweetness by just
about-right (JAR) tests (60 consumers), difference and rejection thresholds (36
and 35 assessors), and acceptance and sensory profile by Check-all-that-apply
(CATA) tests (100 consumers) were performed. JAR test comprised six
concentrations of AS from 12% down to 4.5%. Thresholds tests comprised orange
nectars at reference sugar concentration (10%) and at lower sugar levels.
Acceptance and CATA tests compared reference, ideal sweetness and thresholds
concentrations. There were two groups of consumers; one with ideal sweetness
lower at 5.5% AS and another with ideal sweetness at standard 10.5% AS. The
average ideal sweetness among all consumers was 7.3% AS. The difference threshold
from the reference at 10.5% AS was at 8.5% AS and the rejection threshold was
7.2%. Overall acceptance of nectar with 8.5% and 7.2% AS was similar to reference
and higher than acceptance of nectar with 5.5%. However, after cluster analysis,
nectars with 5.5% AS did not differ from nectars with 8.5% or 7.2% AS, suggesting
the possibility of a gradual reduction until 5.5% in the long term. Lowering AS
to 7.2% or 5.5% caused significant changes in viscosity, sweet odor, bitterness
and sweetness in comparison to the reference concentration. Lowering sugar from
10% to 8.5% did not affect acceptance or sensory attributes, and could be
indicated for a first reduction. Results indicate that a gradual reduction to
7.2% and 5.5% would be feasible. Reductions can remove 3150-9450 tons of sugar
per year from the Brazilian diet resulting in healthier beverages.
PMID- 26428861
TI - Feeding on resistant rice leads to enhanced expression of defender against
apoptotic cell death (OoDAD1) in the Asian rice gall midge.
AB - BACKGROUND: The Asian rice gall midge (Orseolia oryzae) is a destructive insect
pest of rice. Gall midge infestation in rice triggers either compatible or
incompatible interactions leading to survival or mortality of the feeding
maggots, respectively. In incompatible interactions, generation of plant
allelochemicals/defense molecules and/or inability of the maggots to continue
feeding on the host initiate(s) apoptosis within the maggots. Unraveling these
molecular events, triggered within the maggots as a response to feeding on
resistant hosts, will enable us to obtain a better understanding of host
resistance. The present study points towards the likely involvement of a defender
against apoptotic cell death gene (DAD1) in the insect in response to the host
defense. RESULTS: The cDNA coding for the DAD1 orthologue in the rice gall midge
(OoDAD1) consisted of 339 nucleotides with one intron of 85 bp and two exons of
208 and 131 nucleotides. The deduced amino acid sequence of OoDAD1 showed a high
degree of homology (94.6%) with DAD1 orthologue from the Hessian fly (Mayetiola
destructor)--a major dipteran pest of wheat. Southern hybridization analysis
indicated that OoDAD1 was present as a single copy in the genomes of the Asian
rice gall midge biotypes (GMB) 1, 4 and 4 M. In the interactions involving GMB4
with Jaya (susceptible rice host) the expression level of OoDAD1 in feeding
maggots gradually increased to 3-fold at 96 hai (hours after infestation) and
peaked to 3.5-fold at 96 hai when compared to that at 24 hai. In contrast,
expression in maggots feeding on RP2068 (resistant host) showed a steep increase
of more than 8-fold at 24 hai and this level was sustained at 48, 72 and 96 hai
when compared with the level in maggots feeding on Jaya at 24 hai. Recombinant
OoDAD1, expressed in E. coli cells, when injected into rice seedlings induced a
hypersensitive response (HR) in the resistant rice host, RP2068, but not in the
susceptible rice variety, Jaya. CONCLUSIONS: The results indicate that the
expression of OoDAD1 is triggered in the feeding maggots probably due to the host
resistance response and therefore, is likely an important molecule in the initial
stages of the interaction between the midge and its rice host.
PMID- 26428863
TI - Cognitive functions of intracellular mechanisms for contextual amplification.
AB - Evidence for the hypothesis that input to the apical tufts of neocortical
pyramidal cells plays a central role in cognition by amplifying their responses
to feedforward input is reviewed. Apical tufts are electrically remote from the
soma, and their inputs come from diverse sources including direct feedback from
higher cortical regions, indirect feedback via the thalamus, and long-range
lateral connections both within and between cortical regions. This suggests that
input to tuft dendrites may amplify the cell's response to basal inputs that they
receive via layer 4 and which have synapses closer to the soma. ERP data
supporting this inference is noted. Intracellular studies of apical amplification
(AA) and of disamplification by inhibitory interneurons targeted only at tufts
are reviewed. Cognitive processes that have been related to them by
computational, electrophysiological, and psychopathological studies are then
outlined. These processes include: figure-ground segregation and Gestalt
grouping; contextual disambiguation in perception and sentence comprehension;
priming; winner-take-all competition; attention and working memory; setting the
level of consciousness; cognitive control; and learning. It is argued that
theories in cognitive neuroscience should not assume that all neurons function as
integrate-and-fire point processors, but should use the capabilities of cells
with distinct sites of integration for driving and modulatory inputs. Potentially
'unifying' theories that depend upon these capabilities are reviewed. It is
concluded that evolution of the primitives of AA and disamplification in
neocortex may have extended cognitive capabilities beyond those built from the
long-established primitives of excitation, inhibition, and disinhibition.
PMID- 26428864
TI - VIIIth nerve cavernous hemangioma mimicking a stage 1 acoustic schwannoma.
AB - OBJECTIVE: To report a case of VIIIth nerve cavernous hemangioma, a very rare
differential diagnosis among the various pathologies presenting as small
enhancing entities into the internal auditory canal. It is one of the most
challenging when imaging is not able to differentiate it from an intrameatal
vestibular schwannoma. METHODS AND RESULTS: We report a cavernous hemangioma
extruding from the internal auditory canal, diagnosed after a left
translabyrinthine resection in a 45-year-old man complaining of profound
sensorineural hearing loss, with no facial paresis or dizziness. The preoperative
differential diagnosis of a vestibular schwannoma was impossible, due to the
absence of calcifications that usually characterize temporal bone hemangiomas.
Clinical presentation, radiological features and treatment considerations are
discussed along with up-to-date review of pertinent literature. CONCLUSIONS: When
considering an apparent small intra-auditory canal schwannoma, otoneurologists
should be aware of the rare possibility of a cavernous hemangioma. Early
diagnosis and surgical treatment may improve the functional outcome, possibly
preserving neural integrity.
PMID- 26428865
TI - On heart migration of the peritoneal catheter.
PMID- 26428866
TI - Accumulation of free amino acids during exposure to drought in three springtail
species.
AB - Springtails are closely related to insects, but they differ from these with
respect to water balance, in particular because springtails are small and have
high integumental permeability to water. Here we report a series of experiments
addressing the dynamics of osmoregulation, water content and accumulation of free
amino acids (FAAs) in three springtail species during exposure to a gradually
increasing environmental desiccation simulating conditions in drought exposed
soil. Folsomia candida and Protaphorura fimata (both living in the deeper soil
layers; euedaphic species) were active throughout the 3week exposure, with the
developing drought regime ending at -3.56MPa (the soil water activity at the
permanent wilting point of plants is -1.5MPa) and remained hyperosmotic (having
an body fluid osmolality higher than the corresponding environment) to their
surrounding air. Sinella curviseta (living in upper soil/litter layers;
hemiedaphic species) also survived this exposure, but remained hypoosmotic
throughout (i.e. with lower osmolality than the environment). The body content of
most FAAs increased in response to drought in all three species. Alanine, proline
and arginine were the most significantly upregulated FAAs. By combining our
results with data in the literature, we could account for 82% of the observed
osmolality at -3.56MPa in F. candida and 92% in P. fimata. The osmolality of S.
curviseta was only slightly increased under drought, but here FAAs were
considerably more important as osmolytes than in the two other species. We
propose that FAAs probably have general importance in drought tolerance of
springtails.
PMID- 26428867
TI - Isolation and anti-microbial susceptibility pattern of group B Streptococcus
among pregnant women attending antenatal clinics in Ayder Referral Hospital and
Mekelle Health Center, Mekelle, Northern Ethiopia.
AB - BACKGROUND: Vaginal colonization with group B Streptococcus (GBS) is the
predominant risk factor for the development of invasive neonatal GBS diseases and
puts newborns at increased risk for morbidity and mortality. This study is aimed
to determine the colonization rate and antimicrobial susceptibility pattern of
group B Streptococcus among pregnant women. METHODS: Hospital based cross
sectional study was conducted from August to December 2014 at selected health
facilities. A total of 139 antenatal clinics attendees, proportionally allocated,
were recruited consecutively. Socio-demographic and clinical factors were
collected using a structured questionnaire. Vaginal swabs were collected and
cultured on Todd Hewitt broth and in 5 % sheep blood agar. Antimicrobial
susceptibility test was done using Kirby-Bauer disk diffusion test. Statistical
analysis was performed using Pearson's Chi square test. RESULTS: Among the 139,
19 (13.7 %) were positive for GBS. All the GBS isolates were susceptible (100 %)
to penicillin G, vancomycin, ampicillin, erythromycin and gentamicin. Two of the
GBS isolates showed multidrug resistance against norfloxacin and ciprofloxacin.
No statistically significant difference was observed for GBS colonization with
any independent variables. CONCLUSION: Vaginal colonization of GBS for the
present study put emphasis on further investigation and accomplishment of routine
GBS screening practices. The recovery of resistant strains to antimicrobial
agents recommended in cases of penicillin allergic mothers indicates the
importance of susceptibility test.
PMID- 26428868
TI - Diffuse and multifocal nephrogenic adenoma with Familial Mediterranean Fever: a
case report with molecular study.
AB - Nephrogenic adenoma, also referred to nephrogenic metaplasia, is a benign
proliferative lesion of urothelium, usually associated with chronic physical
stimuli or inflammation. Familial Mediterranean fever is an inherited autosomal
recessive disease characterized by recurrent short episodes of fever. The site of
mutation is found in MEFV gene which controls inflammatory responses. We have
experienced a case of nephrogenic adenoma in a 16-year-old girl with Familial
Mediterranean Fever, showing proliferative lesions diffusely in the urinary
bladder and multifocally in the other parts of urinary tract. These lesions
disappeared after colchicine treatment. We searched for MEFV gene mutation using
the specimen from the resected urinary bladder and detected heterozygous mutation
of E148Q. There is a possibility that control of inflammation caused by the
surgery for vesicoureteral reflux in the local site didn't work well on the
background of heterozygous mutation of MEFV gene, and as a result, nephrogenic
adenoma appeared. This is the first report of a combination of two rare diseases.
We have to be aware that nephrogenic adenoma can occur in association with
Familial Mediterranean Fever, and the former condition should be taken into
consideration when rendering a correct pathological diagnosis.
PMID- 26428869
TI - Discovery of dihydroquinazolinone derivatives as potent, selective, and CNS
penetrant M(1) and M(4) muscarinic acetylcholine receptors agonists.
AB - We designed and synthesized a series of dihydroquinazolinone derivatives as
selective M1 and M4 muscarinic acetylcholine receptors agonists. Introduction of
the N-carbethoxy piperidine unit into a HTS hit compound followed by optimization
of the amine linker and the carbamoyl moiety led to the identification of
compound 1 as a potential candidate. The identified compound 1 showed high
selectivity for M1 and M4 muscarinic acetylcholine receptors with M4 partial
agonistic activity. In addition, compound 1 showed good brain penetration and
reversed methamphetamine-induced hyperlocomotion in rats (ED50=3.0 mg/kg, sc).
PMID- 26428870
TI - Rethinking the old antiviral drug moroxydine: Discovery of novel analogues as
anti-hepatitis C virus (HCV) agents.
AB - The discovery of a novel class of HCV inhibitors is described. The new
amidinourea compounds were designed as isosteric analogues of the antiviral drug
moroxydine. The two derivatives 11g and 11h showed excellent HCV inhibition
activity and viability and proved to inhibit a step(s) of the RNA replication.
The new compounds have been synthesized in only three synthetic steps from cheap
building blocks and in high yields, thus turning to be promising drug candidates
in the development of cheaper HCV treatments.
PMID- 26428871
TI - Discovery and structure-activity analysis of 4-((5-nitropyrimidin-4
yl)amino)benzimidamide derivatives as novel protein arginine methyltransferase 1
(PRMT1) inhibitors.
AB - Despite a potential application of PRMT1 inhibitors in cancer treatment, very few
of PRMT1 inhibitors have been reported. To obtain novel potent PRMT1 inhibitors,
structure optimizations towards a hit compound, 4-((6-chloro-5-nitropyrimidin-4
yl)amino)benzimidamide, were carried out. A series of 4-((5-nitropyrimidin-4
yl)amino)benzimidamide derivatives were synthesized. Structure-activity
relationship analysis led to the discovery of a number of PRMT1 inhibitors. The
most potent compound corresponds to compound 6d, which showed an IC50 value of
2.0 MUM against PRMT1. This compound also displayed a considerable anti
proliferative activity against three tumor cell lines, DLD-1, T24 and SH-SY-5Y,
with IC50 values of 4.4 MUM, 13.1 MUM and 11.4 MUM, respectively.
PMID- 26428872
TI - Design, synthesis, and biological evaluation of oxindole derivatives as
antidepressive agents.
AB - The 3-substituted oxindole derivatives were designed, synthesized, and evaluated
for antidepressant activity by employing forced swimming test, tail suspension
test, and MAO-A inhibition assay. Results of biological studies revealed that the
majority of compounds exhibited potent to moderately potent activity and among
them, 12 displayed potency comparable to that of the imipramine with %DID of
37.95 and 44.84 in the FST and TST, respectively. At the same time, imipramine
showed %DID of 43.62 and 50.64 in the FST and TST, correspondingly. In the MAO-A
inhibition assay, 12 showed an IC50 of 18.27 MUmol, whereas the reference drug
moclobemide displayed an IC50 of 13.1 MUmol. The SAR study disclosed that the
presence of bromo atom at the phenyl/furanyl or thienyl moiety in the oxindole
derivatives was critical for the antidepressant activity.
PMID- 26428873
TI - Identification of a molecular target of kurahyne, an apoptosis-inducing
lipopeptide from marine cyanobacterial assemblages.
AB - In 2014, we isolated kurahyne, an acetylene-containing lipopeptide, from a marine
cyanobacterial assemblage of Lyngbya sp. Kurahyne exhibited growth-inhibitory
activity against human cancer cells, and induced apoptosis in HeLa cells.
However, its mode of action is not yet clear. To elucidate its mode of action, we
carried out several cell-based assays, and identified the intracellular target
molecule of kurahyne as sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA). In
addition, we found that kurahyne inhibited the differentiation of macrophages
into osteoclasts.
PMID- 26428874
TI - Exploring clotrimazole-based pharmacophore: 3D-QSAR studies and synthesis of
novel antiplasmodial agents.
AB - We report herein the generation and validation of a 3D-QSAR model based on a set
of antimalarials previously described by us and characterized by a clotrimazole
based pharmacophore. A novel series of derivatives was synthesized and showed
activity against Plasmodium falciparum chloroquine-sensitive (CQ-S) and
chloroquine-resistant (CQ-R) strains. Gratifyingly, compounds 35a-c showed
interesting activity against P. falciparum CQ-R strains with improved predicted
physico-chemical properties.
PMID- 26428875
TI - Palmoplantar eczema as initial sign of mycosis fungoides.
PMID- 26428876
TI - Initiating technical refinements in high-level golfers: Evidence for
contradictory procedures.
AB - When developing motor skills there are several outcomes available to an athlete
depending on their skill status and needs. Whereas the skill acquisition and
performance literature is abundant, an under-researched outcome relates to the
refinement of already acquired and well-established skills. Contrary to current
recommendations for athletes to employ an external focus of attention and a
representative practice design, Carson and Collins' (2011) [Refining and
regaining skills in fixation/diversification stage performers: The Five-A Model.
International Review of Sport and Exercise Psychology, 4, 146-167. doi:
10.1080/1750984x.2011.613682 ] Five-A Model requires an initial narrowed internal
focus on the technical aspect needing refinement: the implication being that
environments which limit external sources of information would be beneficial to
achieving this task. Therefore, the purpose of this paper was to (1) provide a
literature-based explanation for why techniques counter to current
recommendations may be (temporarily) appropriate within the skill refinement
process and (2) provide empirical evidence for such efficacy. Kinematic data and
self-perception reports are provided from high-level golfers attempting to
consciously initiate technical refinements while executing shots onto a driving
range and into a close proximity net (i.e. with limited knowledge of results). It
was hypothesised that greater control over intended refinements would occur when
environmental stimuli were reduced in the most unrepresentative practice
condition (i.e. hitting into a net). Results confirmed this, as evidenced by
reduced intra-individual movement variability for all participants' individual
refinements, despite little or no difference in mental effort reported. This
research offers coaches guidance when working with performers who may find
conscious recall difficult during the skill refinement process.
PMID- 26428877
TI - Admissibility analysis for discrete-time singular systems with randomly occurring
uncertainties via delay-divisioning approach.
AB - This paper deals with the problem of admissibility analysis for discrete-time
singular system with time-delays. The uncertainties occurring in the system
parameters are assumed to be random. By constructing Lyapunov functional,
sufficient delay-dependent stochastic admissibility conditions are established
via delay divisioning approach in terms of linear matrix inequalities (LMIs),
which can be easily checked by utilizing the numerically efficient Matlab LMI
toolbox. Numerical examples and their simulation results are given to illustrate
the effectiveness of the obtained theoretical results.
PMID- 26428878
TI - Fault tolerant control based on interval type-2 fuzzy sliding mode controller for
coaxial trirotor aircraft.
AB - In this paper, a robust controller for a Six Degrees of Freedom (6 DOF) coaxial
trirotor helicopter control is proposed in presence of defects in the system. A
control strategy based on the coupling of the interval type-2 fuzzy logic control
and sliding mode control technique are used to design a controller. The main
purpose of this work is to eliminate the chattering phenomenon and guaranteeing
the stability and the robustness of the system. In order to achieve this goal,
interval type-2 fuzzy logic control has been used to generate the discontinuous
control signal. The simulation results have shown that the proposed control
strategy can greatly alleviate the chattering effect, and perform good reference
tracking in presence of defects in the system.
PMID- 26428879
TI - Delayed Stenosis in the Intracranial Vessels following Endovascular Treatment for
Acute Stroke.
AB - PURPOSE: To evaluate delayed stenosis of the vessels after endovascular
thrombectomy using magnetic resonance (MR) angiography. MATERIALS AND METHODS: Of
82 consecutive patients who underwent successful endovascular treatment for acute
intracranial large vessel occlusion between October 2010 and October 2014 at a
single institution, 57 patients for whom 3-month radiologic follow-up
examinations using MR angiography were available were included in the analysis.
MR angiography images were assessed to detect delayed stenosis, which was defined
as a decrease in the diameter of treated vessels > 50% compared with MR
angiography images obtained 24 hours after endovascular treatment. RESULTS: MR
angiography images obtained 3 months after endovascular treatment revealed
delayed stenosis of treated vessels in five (8.8%) of 57 patients. All cases of
delayed stenosis were asymptomatic and occurred in the middle cerebral artery
(MCA). Further serial radiologic follow-up showed gradual improvement of all
delayed stenosis over 12 months. CONCLUSIONS: Endovascular treatment poses a risk
of delayed stenosis of treated vessels, especially in the MCA. MR angiography is
a useful modality in long-term follow-up to evaluate delayed stenosis after
endovascular treatment.
PMID- 26428880
TI - Comparative Analysis of Prostate Volume as a Predictor of Outcome in Prostate
Artery Embolization.
AB - PURPOSE: To determine the role of prostate volume as a predictor of outcome after
prostatic artery embolization (PAE). MATERIALS AND METHODS: From January 2012 to
September 2014, 78 consecutive patients undergoing PAE were evaluated at baseline
and 1, 3, and 6 months. Analysis was performed comparing prostate volume groups
(group 1, < 50 cm3; group 2, 50-80 cm(3); group 3, > 80 cm3) at baseline and
follow-up to assess for differences in outcomes of American Urological
Association (AUA) symptom index, quality of life (QOL)-related symptoms, and
International Index of Erectile Function (IIEF). RESULTS: Mean baseline prostate
volumes were 37.5 cm(3) in group 1 (n = 16), 65.7 cm3 in group 2 (n = 26), and
139.4 cm3 in group 3 (n = 36). There were no significant differences in baseline
age, AUA symptom index, QOL, or IIEF between groups. Bilateral embolization was
successful in 75 of 78 patients (96%). Two patients underwent unilateral
embolization, and treatment failed in one patient as a result of bilateral
atherosclerotic occlusion. A significant reduction in AUA symptom index was
achieved within groups from baseline to 1, 3, and 6 months (n = 77): in group 1,
from 27.2 to 14.0, 12.9, and 15.9, respectively (P = .002); in group 2, from 25.6
to 17.1, 16.3, and 13.5, respectively (P < .0001); and in group 3, from 26.5 to
15.2, 12.5, and 13.6, respectively (P < .0001). There was also a significant
improvement in QOL. Comparative analysis demonstrated no statistically
significant differences in AUA symptom index, QOL, or IIEF between groups. Two
minor complications occurred: groin hematoma and a urinary tract infection.
CONCLUSIONS: PAE offers similar clinical benefits to patients with differing
gland sizes and may offer a reasonable alternative for poor candidates for
urologic surgery.
PMID- 26428881
TI - Histochemical detection of acetogenins and storage molecules in the endosperm of
Annona macroprophyllata Donn Sm. seeds.
AB - Acetogenins (ACGs) are bioactive compounds with cytotoxic properties in different
cell lines. They are antitumoural, antiparasitic, antimalarial, insecticidal,
antimicrobial, antifungal and antibacterial. These secondary metabolites function
in plant defence and are found in specific organelles and specific cells, thereby
preventing toxicity to the plant itself and permitting site-specific defence. The
aim of this work was to histochemically determine the in situ localisation of
ACGs in the endosperm of Annona macroprophyllata seeds using Kedde's reagent.
Additionally, the colocalisation of ACGs with other storage molecules was
analysed. The seeds were analysed after 6 and 10 days of imbibition, when 1 or 2
cm of the radicle had emerged and metabolism was fully established. The seeds
were then transversally cut in half at the midline and processed using different
histological and histochemical techniques. Positive reactions with Kedde's
reagent were only observed in fresh, unfixed sections that were preserved in
water, and staining was found only in the large cells (the idioblasts) at the
periphery of the endosperm. The ACGs' positive reaction with Sudan III
corroborated their lipid nature. Paraffin sections stained with Naphthol Blue
Black showed reactions in the endosperm parenchyma cells and stained the
proteoplasts blue, indicating that they might correspond to storage sites for
albumin-like proteins. Lugol's iodine, which is similar in chemical composition
to Wagner's reagent, caused a golden brown reaction product in the cytoplasm of
the idioblasts, which may indicate the presence of alkaloids. Based on these
results, we propose that Kedde's reagent is an appropriate histochemical stain
for detecting ACGs in situ in idioblasts and that idioblasts store ACGs and
probably alkaloids. ACGs that are located in idioblasts found in restricted,
peripheral areas of the endosperm could serve as a barrier that protects the
seeds against insects and pathogen attack.
PMID- 26428882
TI - Apoptosis activation in human carious dentin. An immunohistochemical study.
AB - The exact mechanisms and enzymes involved in caries progression are largely
unclear. Apoptosis plays a key role in dentin remodelling related to damage
repair; however, it is unclear whether apoptosis in decayed teeth is activated
through the extrinsic or the intrinsic pathway. This ex vivo immunohistochemical
study explored the localization of TRAIL, DR5, Bcl-2 and Bax, the main proteins
involved in apoptosis, in teeth with advanced caries. To evaluate TRAIL, DR5, Bcl
2 and Bax immunoexpressions twelve permanent carious premolars were embedded in
paraffin and processed for immunohistochemistry. The results showed that TRAIL
and DR5 were overexpressed in dentin and in pulp vessels and mononuclear cells;
strong Bax immunostaining was detected in dilated dentinal tubules close to the
lesion, and Bcl-2 staining was weak in some dentin areas under the cavity or
altogether absent. These findings suggest that both apoptosis pathways are
activated in dental caries. Further studies are required to gain insights into
its biomolecular mechanisms.
PMID- 26428854
TI - Time-series metagenomic analysis reveals robustness of soil microbiome against
chemical disturbance.
AB - Soil microbial communities have great potential for bioremediation of
recalcitrant aromatic compounds. However, it is unclear which taxa and genes in
the communities, and how they contribute to the bioremediation in the polluted
soils. To get clues about this fundamental question here, time-course (up to 24
weeks) metagenomic analysis of microbial community in a closed soil microcosm
artificially polluted with four aromatic compounds, including phenanthrene, was
conducted to investigate the changes in the community structures and gene pools.
The pollution led to drastic changes in the community structures and the gene
sets for pollutant degradation. Complete degradation of phenanthrene was strongly
suggested to occur by the syntrophic metabolism by Mycobacterium and the most
proliferating genus, Burkholderia. The community structure at Week 24 (~12 weeks
after disappearance of the pollutants) returned to the structure similar to that
before pollution. Our time-course metagenomic analysis of phage genes strongly
suggested the involvement of the 'kill-the-winner' phenomenon (i.e. phage
predation of Burkholderia cells) for the returning of the microbial community
structure. The pollution resulted in a decrease in taxonomic diversity and a
drastic increase in diversity of gene pools in the communities, showing the
functional redundancy and robustness of the communities against chemical
disturbance.
PMID- 26428883
TI - Sox9 expression in canine epithelial skin tumors.
AB - Sox9 is a master regulatory gene involved in developmental processes, stem cells
maintenance and tumorigenesis. This gene is expressed in healthy skin but even in
several skin neoplasms, where its expression patterns often resembles those of
the developing hair follicle. In this study, samples from eleven different types
of canine skin neoplasms (squamous papilloma, squamous cell carcinoma,
infundibular keratinizing acanthoma, inferior tricholemmoma, isthmic
tricholemmoma, trichoblastoma, trichoepitelioma, malignant trichoepitelioma,
pilomatricoma, subungual keratoacanthoma, subungual squamous cell carcinoma) were
immunohistochemically stained and evaluated for Sox9 with the aim to correlate
tumor phenotype with molecular characteristics that may help to better define
tumor development, contribute to its diagnosis and clinical management.
Keratoacanthoma excluded, all the skin neoplasms examined showed a variable
positivity to Sox9, especially in the basal layers, but with major intensity in
neoplasms developing from the bulge region of the hair follicle, as
trichoblastoma. According to our results, Sox9 could be employed as a stem cell
marker to better assess the role of stem cells in canine epidermal and follicular
tumors.
PMID- 26428884
TI - Enhancement of immunohistochemical detection of Salmonella in tissues of
experimentally infected pigs.
AB - Salmonella Typhimurium is one of the main pathogens compromising porcine and
human health as well as food safety, because it is a prevailing source of
foodborne infections due to contaminated pork. A prominent problem in the
management of this bacteriosis is the number of subclinically infected carrier
pigs. As very little is known concerning the mechanisms allowing Salmonella to
persist in pigs, the objective of this study was to develop an
immunohistochemical approach for the detection of salmonellae in tissue of pigs
experimentally infected with Salmonella Typhimurium. Samples were obtained from a
challenge trial in which piglets of the German Landrace were intragastrically
infected with Salmonella enterica serovar Typhimurium DT104 (1.4-2.1x1010 CFU).
Piglets were sacrificed on days 2 and 28 post infection. Tissue samples of
jejunum, ileum, colon, ileocecal mesenteric lymph nodes (Lnn. ileocolici), and
tonsils (Tonsilla veli palatini) were fixed in Zamboni's fixative and paraffin
embedded. Different immunohistochemical staining protocols were evaluated.
Salmonella was detected in varying amounts in the tissues. Brown iron-containing
pigments in the lymph nodes interfered with the identification of Salmonella if
DAB was used as a staining reagent. Detergents like Triton X-100 or Saponin
enhanced the sensitivity. It seems advisable not to use a detection system with
brown staining for bacteria in an experimental setup involving intestinal damage
including haemorrhage. The use of detergents appears to result in a higher
sensitivity in the immunohistochemical detection of salmonellae.
PMID- 26428885
TI - Heterogeneous vesicles in mucous epithelial cells of posterior esophagus of
Chinese giant salamander (Andrias davidianus).
AB - The Chinese giant salamander belongs to an old lineage of salamanders and
endangered species. Many studies of breeding and disease regarding this amphibian
had been implemented. However, the studies on the ultrastructure of this
amphibian are rare. In this work, we provide a histological and ultrastructural
investigation on posterior esophagus of Chinese giant salamander. The sections of
amphibian esophagus were stained by hematoxylin & eosin (H&E). Moreover, the
esophageal epithelium was observed by transmission electron microscopy (TEM). The
results showed that esophageal epithelium was a single layer epithelium, which
consisted of mucous cells and columnar cells. The esophageal glands were present
in submucosa. The columnar cells were ciliated. According to the diverging
ultrastructure of mucous vesicles, three types of mucous cells could be
identified in the esophageal mucosa: i) electron-lucent vesicles mucous cell (ELV
MC); ii) electron-dense vesicles mucous cell (EDV-MC); and iii) mixed vesicles
mucous cell (MV-MC).
PMID- 26428886
TI - Testicular expression of NGF, TrkA and p75 during seasonal spermatogenesis of the
wild ground squirrel (Citellus dauricus Brandt).
AB - The nerve growth factor (NGF) not only has an essential effect on the nervous
system, but also plays an important role in a variety of non-neuronal systems,
such as the reproductive system. The aim of this study was to investigate the
seasonal changes in expression of NGF and its receptors (TrkA and p75) in testes
of the wild ground squirrel during the breeding and nonbreeding seasons.
Immunolocalization for NGF was detected mainly in Leydig cells and Sertoli cells
in testes of the breeding and nonbreeding seasons. The immunoreactivity of TrkA
was highest in the elongated spermatids, whereas p75 in spermatogonia and
spermatocytes in testes of the breeding season. In the nonbreeding season testes,
TrkA showed positive immunostainings in Leydig cells, spermatogonia and primary
spermatocytes, while p75 showed positive signals in spermatogonia and primary
spermatocytes. Consistent with the immunohistochemical results, the mean mRNA and
protein level of NGF and TrkA were higher in the testes of the breeding season,
and then decreased to a relatively low level in the nonbreeding season. In
addition, the concentration of plasma gonadotropins and testosterone were assayed
by radioimmunoassay (RIA), and the results showed a significant seasonal change
between the breeding and nonbreeding seasons. To conclude, these results of this
study provide the first evidence on the potential involvement of NGF and its
receptor, TrkA and p75 in the seasonal spermatogenesis and testicular function
change of the wild ground squirrel.
PMID- 26428887
TI - Immunohistochemical demonstration of specific antigens in the human brain fixed
in zinc-ethanol-formaldehyde.
AB - Tissue fixation is critical for immunohistochemistry. Recently, we developed a
zinc-ethanol-formalin fixative (ZEF), and the present study was aimed to assess
the applicability of the ZEF for the human brain histology and
immunohistochemistry and to evaluate the detectability of different antigens in
the human brain fixed with ZEF. In total, 11 antigens were tested, including
NeuN, neuron-specific enolase, GFAP, Iba-1, calbindin, calretinin, choline
acetyltransferase, glutamic acid decarboxylase (GAD65), tyrosine hydroxylase,
synaptophysin, and alpha-tubulin. The obtained data show that: i) the ZEF has
potential for use in general histological practice, where detailed
characterization of human brain morphology is needed; ii) the antigens tested are
well-preserved in the human brain specimens fixed in the ZEF.
PMID- 26428888
TI - Immunohistochemical and ultrastructural study of the lamellae of oocytes in
atretic follicles in relation to different processes of cell death.
AB - Atresia is the process through which non-selectable oocytes are eliminated; it
involves apoptosis and/or autophagy. This study used immunohistochemical and
ultrastructural techniques to characterize the lamellae present in the cytoplasm
of oocytes in follicles in the process of atresia in prepubertal and adult Wistar
rats. The results indicate that the lamellae are positive to tubulin and myosin
immunodetection under light and electron microscopy. Labeling is greater with
anti-tubulin and lesser with anti-myosin. Our observations indicate that lamellae
are present in oocytes at the initial antral stage in prepubertal rats; that is,
from day 14 post-birth to adult age. We were able to determine that the increase
in altered lamellae principally occurs in the apoptotic cells rather than in the
autophagic cells.
PMID- 26428889
TI - Three-dimensional apoptotic nuclear behavior analyzed by means of Field Emission
in Lens Scanning Electron Microscope.
AB - Apoptosis is an essential biological function required during embryogenesis,
tissue homeostasis, organ development and immune system regulation. It is an
active cell death pathway involved in a variety of pathological conditions.
During this process cytoskeletal proteins appear damaged and undergo an enzymatic
disassembling, leading to formation of apoptotic features. This study was
designed to examine the three-dimensional chromatin behavior and cytoskeleton
involvement, in particular actin re-modeling. HL-60 cells, exposed to
hyperthermia, a known apoptotic trigger, were examined by means of a Field
Emission in Lens Scanning Electron Microscope (FEISEM). Ultrastructural
observations revealed in treated cells the presence of apoptotic patterns after
hyperthermia trigger. In particular, three-dimensional apoptotic chromatin
rearrangements appeared involving the translocation of filamentous actin from
cytoplasm to the nucleus. FEISEM immunogold techniques showed actin labeling and
its precise three-dimensional localization in the diffuse chromatin, well
separated from the condensed one. The actin presence in dispersed chromatin
inside the apoptotic nucleus can be considered an important feature,
indispensable to permit the apoptotic machinery evolution.
PMID- 26428890
TI - Immunohistochemical localization of periostin in human gingiva.
AB - The periostin is a matricellular protein expressed in collagen-rich tissues
including some dental and periodontal tissues where it is regulated by mechanical
forces, growth factors and cytokines. Interestingly the expression of this
protein has been found modified in different gingival pathologies although the
expression of periostin in normal human gingiva was never investigated. Here we
used Western blot and double immunofluorescence coupled to laser-confocal
microscopy to investigated the occurrence and distribution of periostin in
different segments of the human gingival in healthy subjects. By Western blot a
protein band with an estimated molecular mass of 94 kDa was observed. Periostin
was localized at the epithelial-connective tissue junction, or among the fibers
of the periodontal ligament, and never co-localized with cytokeratin or vimentin
thus suggesting it is an extracellular protein. These results demonstrate the
occurrence of periostin in adult human gingiva; its localization suggests a role
in the bidirectional interactions between the connective tissue and the
epithelial cells, and therefore in the physiopathological conditions in which
these interactions are altered.
PMID- 26428891
TI - An in situ hybridization study of perlecan, DMP1, and MEPE in developing condylar
cartilage of the fetal mouse mandible and limb bud cartilage.
AB - The main purpose of this in situ hybridization study was to investigate mRNA
expression of three bone/cartilage matrix components (perlecan, DMP1, and MEPE)
in developing primary (tibial) and secondary (condylar) cartilage. Perlecan mRNA
expression was first detected in newly formed chondrocytes in tibial cartilage at
E13.0, but this expression decreased in hypertrophic chondrocytes at E14.0. In
contrast, at E15.0, perlecan mRNA was first detected in the newly formed
chondrocytes of condylar cartilage; these chondrocytes had characteristics of
hypertrophic chondrocytes, which confirmed the previous observation that
progenitor cells of developing secondary cartilage rapidly differentiate into
hypertrophic chondrocytes. DMP1 mRNA was detected in many chondrocytes within the
lower hypertrophic cell zone in tibial cartilage at E14.0. In contrast, DMP1 mRNA
expression was only transiently detected in a few chondrocytes of condylar
cartilage at E15.0. Thus, DMP1 may be less important in the developing condylar
cartilage than in the tibial cartilage. Another purpose of this study was to test
the hypothesis that MEPE may be a useful marker molecule for cartilage. MEPE mRNA
was not detected in any chondrocytes in either tibial or condylar cartilage;
however, MEPE immunoreactivity was detected throughout the cartilage matrix.
Western immunoblot analysis demonstrated that MEPE antibody recognized two bands,
one of 67 kDa and another of 59 kDa, in cartilage-derived samples. Thus MEPE
protein may gradually accumulate in the cartilage, even though mRNA expression
levels were below the limits of detection of in situ hybridization. Ultimately,
we could not designate MEPE as a marker molecule for cartilage, and would modify
our original hypothesis.
PMID- 26428892
TI - Elevation of pivaloylcarnitine by sivelestat sodium in two children.
AB - BACKGROUND: Sivelestat sodium (sivelestat), a neutrophil elastase inhibitor, is
used to treat acute respiratory distress syndrome (ARDS). We report two cases
that developed elevated C5-acylcarnitine (C5-AC) levels following treatment with
sivelestat. Case 1 was a 14-day-old female infant born at 25 weeks and 1 day of
gestation who was treated with sivelestat for the prophylaxis of Wilson-Mikity
syndrome soon after birth. Isovaleric acidemia (IVA) was suspected based on a
newborn screening using tandem mass spectrometry (MS/MS). Her C5-AC level was
elevated to 4.49 MUM (cut-off, <1.0) after treatment with sivelestat. Case 2 was
a 4-year-old female with pneumocystis pneumonia that developed during
chemotherapy for disseminated medulloblastoma. Sivelestat was given for the
complication of ARDS. Her C5-AC level increased (1.09 MUM) after eight days of
treatment with sivelestat. RESULTS: In both cases, IVA was ruled out because
isovalerylglycine was not observed in the urinary organic acid analysis. Case 1
was associated with carnitine deficiency (C0 9.16 MUM; reference value, 10-60).
Liquid chromatography-MS/MS confirmed elevated pivaloylcarnitine (PVC) in both
cases. DISCUSSION: Similar to antibiotics containing pivalic acid (PVA),
sivelestat contains PVA, which has the potential to cause secondary carnitine
deficiency. In addition, elevated PVC can lead to false positive findings of IVA
in newborns screened using MS/MS.
PMID- 26428893
TI - In vivo delivery and long-term tissue retention of nano-encapsulated sirolimus
using a novel porous balloon angioplasty system.
AB - AIMS: Among antirestenotic compounds, sirolimus displays a superior safety
profile compared to paclitaxel, but its pharmacokinetic properties make it a
challenging therapeutic candidate for single-time delivery. Herein we evaluate
the feasibility of delivery, long-term retention and vascular effects of
sirolimus nanoparticles delivered through a novel porous angioplasty balloon in
normal porcine arteries and in a swine model of in-stent restenosis (ISR).
METHODS AND RESULTS: Sirolimus nanoparticle formulation was delivered via porous
balloon angioplasty to 753 coronary artery segments for pharmacokinetic studies
and 26 segments for biological effect of sirolimus delivery in different clinical
scenarios (de novo [n=8], ISR [n=6] and following stent implantation [n=12]).
Sirolimus coronary artery concentrations were above the target therapeutic level
of 1 ng/mg after 26 days, and were >100-fold higher in coronary artery treatment
sites than in distal myocardium and remote tissues at all time points. At 28
days, reduction in percent stenosis in formulation-treated sites compared to
balloon angioplasty treatment was noted in all three clinical scenarios, with the
largest effect seen in the de novo study. CONCLUSIONS: Local coronary delivery of
sirolimus nanoparticles in the porcine model using a novel porous balloon
delivery system achieved therapeutic long-term intra-arterial drug levels without
significant systemic residual exposure.
PMID- 26428894
TI - Associations between parental rules, style of communication and children's screen
time.
AB - BACKGROUND: Research suggests an inverse association between parental rules and
screen time in pre-adolescents, and that parents' style of communication with
their children is related to the children's time spent watching TV. The aims of
this study were to examine associations of parental rules and parental style of
communication with children's screen time and perceived excessive screen time in
five European countries. METHODS: UP4FUN was a multi-centre, cluster randomised
controlled trial with pre- and post-test measurements in each of five countries;
Belgium, Germany, Greece, Hungary and Norway. Questionnaires were completed by
the children at school and the parent questionnaire was brought home. Three
structural equation models were tested based on measures of screen time and
parental style of communication from the pre-test questionnaires. DISCUSSION: Of
the 152 schools invited, 62 (41 %) schools agreed to participate. In total 3325
children (average age 11.2 years and 51 % girls) and 3038 parents (81 % mothers)
completed the pre-test questionnaire. The average TV/DVD times across the
countries were between 1.5 and 1.8 h/day, while less time was used for
computer/games console (0.9-1.4 h/day). The children's perceived parental style
of communication was quite consistent for TV/DVD and computer/games console. The
presence of rules was significantly associated with less time watching TV/DVD and
use of computer/games console time. Moreover, the use of an autonomy-supportive
style was negatively related to both time watching TV/DVD and use of
computer/games console time. The use of a controlling style was related
positively to perceived excessive time used on TV/DVD and excessive time used on
computer/games console. With a few exceptions, results were similar across the
five countries. CONCLUSIONS: This study suggests that an autonomy-supportive
style of communicating rules for TV/DVD or computer/ games console use is
negatively related to children's time watching TV/DVD and use of computer/games
console time. In contrast, a controlling style is associated with more screen
time and with more perceived excessive screen time in particular. Longitudinal
research is needed to further examine effects of parental style of communication
on children's screen time as well as possible reciprocal effects. TRIAL
REGISTRATION: International Standard Randomized Controlled Trial Number Register,
registration number: ISRCTN34562078 . Date applied29/07/2011, Date
assigned11/10/2011.
PMID- 26428895
TI - Taurodontism in patients with nonsyndromic cleft lip and palate in a Brazilian
population: a case control evaluation with panoramic radiographs.
AB - OBJECTIVES: The purpose of this study was to evaluate the prevalence of
taurodontism in patients with nonsyndromic cleft lip and palate (NSCLP) within a
Brazilian population. STUDY DESIGN: The study was designed as an epidemiologic
case-control single-center study. Three hundred eighty-eight patients were
included: 88 had NSCLP, and 300 comprised the control group. The first and second
permanent mandibular molars were included in this study. By using panoramic
radiographs, taurodontism was categorized as mesotaurodontism, hypotaurodontism,
and hypertaurodontism. RESULTS: Seventy patients (23.3%) from the control group
and 36 patients (40.9%) from the case group presented taurodontism (P < .001). In
the control group, 108 (9%) teeth showed taurodontism, whereas in the case group
with cleft lip and palate (CLP), 64 (18.2%) teeth showed dental anomalies (P <
.001). In both groups, most taurodontic teeth presented hypotaurodontism,
followed by mesotaurodontism, while hypertaurodontism was found in only two
teeth. The probability of taurodontism in patients with cleft lip (CL) was 2.36
(P = .010) times higher compared with those with CLP, whereas the occurrence of
taurodontism in patients with cleft palate (CP) was 3.15 (P = .002) times greater
than in patients with CLP. CONCLUSIONS: The results from this study indicate a
close relationship between taurodontism and NSCLP and the possibility of
different cleft subphenotypes.
PMID- 26428896
TI - Long-term outcome of transendoscopic oesophageal mass ablation in dogs with
Spirocerca lupi-associated oesophageal sarcoma.
AB - Oesophageal sarcoma is a potential sequel of Spirocerca lupi infection.
Oesophageal mass excision can be performed by open chest surgery. The objectives
of this observational study were to evaluate the feasibility, short-term
morbidity and long-term outcome of transendoscopic oesophageal mass ablation in
dogs with spirocercosis-associated oesophageal neoplasia. A 9 mm video-endoscope
and laser or electrocauterisation were used to debulk the oesophageal mass. Long
term follow-up was done by telephonic interviews. Fifteen dogs were included. The
median tumour size was 5 cm (range 3.5-9). The median procedure time was 75
minutes (range 35-165) and was deemed successful in 12/15 dogs (80 per cent).
Recovery was uneventful in all dogs. Immediate complications included oesophageal
damage (two dogs) oesophageal perforation (one dog) and a focal thermal damage
(one dog). The median hospitalisation time of all dogs was less than one day,
with all but two discharged on the procedure day. The median survival time,
available in nine dogs that were followed, was 202 days (range 51-691). Four of
these dogs (44 per cent) survived more than six months, of which three survived
more than one year. In conclusion, transendoscopic oesophageal mass ablation
might be considered an alternative, palliative procedure for open-chest
oesophageal surgery. It has comparable long-term survival, lower morbidity, short
hospitalisation time and relatively low cost.
PMID- 26428897
TI - Chlamydiae in corvids.
PMID- 26428898
TI - Clostridium perfringens type-D enterotoxaemia in cattle: the diagnostic
significance of intestinal epsilon toxin.
AB - The aims of this study were to describe 42 cases of Clostridium perfringens type
D enterotoxaemia in cattle seen between 2003 and 2014 and to determine the
diagnostic value of detecting epsilon toxin in bovine intestinal content. All
cases in the series had histological brain changes considered pathognomonic for
C. perfringens type-D enterotoxaemia in sheep and goats and the epsilon toxin of
C. perfringens was concurrently detected in the intestinal contents of 15 (36 per
cent) cases. The data from the case series indicate that intestinal epsilon toxin
has a sensitivity of 56 per cent compared with histology of the brain for
diagnosis of bovine C. perfringens type-D enterotoxaemia. The diagnostic
specificity of detecting epsilon toxin in bovine intestinal content was
investigated by screening intestinal contents of 60 bovine carcases submitted for
postmortem examination. Epsilon toxin was detected in 11 (18 per cent) carcases
but no pathognomonic histological brain change was found in any. The specificity
of intestinal epsilon toxin was estimated to be 80.4 per cent. These studies
demonstrate that for a definitive diagnosis of C. perfringens type-D
enterotoxaemia in cattle histological examination of the brain is essential as
the presence of epsilon toxin in the intestinal contents alone is neither
sensitive nor specific enough.
PMID- 26428899
TI - Relationship of Sit-to-Stand Lower-Body Power With Functional Fitness Measures
Among Older Adults With and Without Sarcopenia.
AB - BACKGROUND AND PURPOSE: When evaluating health in older adults, batteries of
tests are typically utilized to assess functional fitness. Unfortunately,
physician's visits are time-sensitive, and it may be important to develop faster
methods to assess functional fitness that can be utilized in professional or
clinical settings. Therefore, the purpose of this investigation was to examine
the relationship of sit-to-stand (STS) power generated through the STS task with
previously established measures of functional fitness, specifically strength,
endurance, speed, agility, and flexibility in older adults with and without
sarcopenia. METHODS: This study consisted of 57 community-dwelling older adults
(n = 16 males; n = 41 females). Functional fitness was assessed using the Short
Physical Performance Battery (SPPB), Senior Fitness Test, handgrip, gait speed
(habitual and maximal), balance, and STS power generated via the Tendo
Weightlifting Analyzer. On the basis of data distribution, second-degree
polynomial (quadratic) curvilinear models (lines of best fit) were applied for
the relationships of 5-time STS time with average and peak power. Zero-order
correlations were evaluated between STS power and all other functional fitness
measures. Older adults with sarcopenia were also identified (n = 15), and
relationships were reevaluated within this subset. RESULTS: STS power (average
and peak) was significantly (P <= .01) correlated with physical performance
measured via previously established assessments. For average power, this was
observed during the senior fitness test (6-minute walk [r = 0.39], 8-ft up-and-go
[r = -0.46], arm curl [r = 0.46], and chair stand [r = 0.55]), SPPB (5-time STS
time [r = -0.63] and 8-ft walk [r = -0.32]), and other independent functional
fitness measures (grip strength [r = 0.65] and maximal gait speed [r = -0.31]).
Similar results were observed for peak power during the senior fitness test (6
minute walk [r = 0.39], 8-ft up-and-go [r = -0.46], arm curl [r = 0.45], chair
stand [r = 0.52], and sit-and-reach [r = -0.27]), SPPB (5-time STS time [r =
0.60] and 8-ft walk [r = -0.33]), and other independent functional fitness
measures (grip strength [r = 0.70] and maximal gait speed [r = -0.32]). Within
the sarcopenic subset, for average and peak power, respectively, significant
relationships were still retained for handgrip strength (r = 0.57 and r = 0.57),
6-minute walk (r = 0.55 and r = 0.61), chair stand (r = 0.76 and r = 0.81), and 5
time STS time (r = -0.76 and r = -0.80) tests. DISCUSSION/CONCLUSIONS: STS power
generated via the STS task significantly relates to commonly administered
functional fitness measures. These relationships also appear to exist when
evaluating these relationships in older adults with sarcopenia. STS power may be
utilized as an independent measure of functional fitness that is feasible to
incorporate in clinical settings where time and space are often limiting factors.
PMID- 26428900
TI - Comparative Analysis of High-Velocity Versus Low-Velocity Exercise on Outcomes
After Total Knee Arthroplasty: A Randomized Clinical Trial.
AB - BACKGROUND AND PURPOSE: High-velocity (HV) exercise is defined as performing a
concentric muscle contraction as fast as possible, or in 1 second or less. Low
velocity (LV) exercise is defined as using 2 seconds to complete the contraction.
A comparison of HV to LV exercise performed by community dwelling older adults
indicates that HV exercise produces greater gains in power and scores for the 8
ft up-and-go, 30-seond chair stand, and continuous scale physical function
performance tests. The effectiveness of HV strengthening exercises has not been
identified for individuals who undergo total knee arthroplasty (TKA). The purpose
of this research study was to compare the effects of a 6-week exercise program,
using either LV or HV contractions, on functional performance, gait, and pain of
individuals who have undergone TKA. METHODS: Adults aged 60 to 89 years with a
mean (standard deviation) age of 71.2 (6.8) years who underwent TKA an average of
15 days prior were randomly assigned to an HV exercise (n = 19) or LV exercise (n
= 19) training group. The training program lasted for 12 sessions, over 6 to 7
weeks. The primary outcome was functional performance rated with the 6-Minute
Walk Test. Secondary measures were the stair climb test, Timed Up and Go test,
gait velocity, gait deviations measured with the Gait Abnormality Rating Scale,
and pain via a visual analog scale. A 2*2 mixed model analysis of variance (group
* time) was used for all outcomes. Comparison between LV and HV groups for
posttest gait velocity and Gait Abnormality Rating Scale used independent t test
and Mann-Whitney U test, respectively. RESULTS: At baseline no differences
between groups were noted for sex, age, and height. The LV group weighed more and
had more comorbid conditions. Spearman's rho demonstrated that the greater
comorbidities of the LV group correlated with a slower stair climb test at
baseline. At posttest both groups exhibited significantly improved scores for all
outcome measurements except the visual analog scale for pain. The HV group, but
not the LV group, reported a significant decrease in pain at the end of the 6
week training program. CONCLUSIONS: Both HV and LV progressive exercises equally
improve functional performance. Only the HV group reported significantly
decreased pain at posttest.
PMID- 26428901
TI - Accelerometer-Based Monitoring of Upper Limb Movement in Older Adults With Acute
and Subacute Stroke.
AB - BACKGROUND AND PURPOSE: Use of the affected extremity during daily life is
important if disuse atrophy is to be prevented after stroke. This study examined
whether objectively measured real-world upper limb movement is associated with
the amount of use of the affected upper limb, as assessed by a standardized
assessment tool in older adults with acute or subacute stroke. This study also
examined whether the real-world upper limb movement is associated with the extent
of impairment of upper and lower extremities. METHODS: The participants were 19
older adults with hemiparesis from acute or subacute stroke [17 (7) days after
the stroke]. All the participants wore 3 accelerometers-1 on each wrist
(bilateral accelerometry) and 1 on the waist-throughout a 24-hour period. They
were interviewed about use of their upper limb in the real-world setting using a
Motor Activity Log. Functions of the affected upper limb or upper and lower limbs
were assessed using the National Institute of Health Stroke Scale, the Brunnstrom
Recovery Stage (BRS), the Simple Test for Evaluating Hand Function, and the
Functional Independence Measure tests. RESULTS AND DISCUSSION: Movement counts
measured with the wrist accelerometer on the affected upper limb (unilateral
accelerometry) over 24 hours and during the 12-hour daytime period (08:00 to
20:00) were significantly correlated with scores for affected upper limb use (the
Motor Activity Log) and functions (the upper extremity BRS and the affected side
Simple Test for Evaluating Hand Function), upper and lower extremity functions
(the National Institute of Health Stroke Scale, the lower extremity BRS, and the
motor Functional Independence Measure), and step counts measured over the same
period. To estimate the affected upper limb use or disuse, we subtracted the
movement counts of the unaffected upper limb from those of the affected upper
limb. As a result, the subtracted counts over 24 hours and during the 12-hour
daytime period were only related to scores for affected upper limb use and
functions. CONCLUSIONS: Bilateral accelerometry for monitoring upper limb
movements in a real-world setting might be useful to clinicians for objective
assessment of affected upper limb use or disuse and function among older adults
with hemiparesis from acute or subacute stroke.
PMID- 26428902
TI - Test-Retest Reliability and Minimal Detectable Change for the 10-Meter Walk Test
in Older Adults With Parkinson's disease.
AB - BACKGROUND AND PURPOSE: Measurement of gait performance in individuals with
Parkinson's disease (PD) can be challenging because of the daily fluctuations in
performance and the progressive nature of the condition. The 10-Meter Walk Test
(10MWT) is commonly used to measure gait speed of individuals with gait
limitations. Existing research on the 10MWT in individuals with PD controls for
many variables inherent to this condition, rendering the results of this test in
settings where these variables are not controlled questionable. The purpose of
this study was to estimate under commonly encountered clinical conditions the
test-retest reliability and the minimal detectable change (MDC) of gait speed and
step frequency determined during the 10MWT in individuals with PD. METHODS: The
10MWT was administered by 2 testers, on 35 participants, across 2 sessions,
separated by 5 to 14 days. Gait speed was measured using a hand-held stopwatch,
and step frequency was assessed through visual observation. Test-retest
reliability was calculated using the intraclass correlation coefficient (ICC) and
the MDC was calculated using the standard error of measurement (SEM). RESULTS AND
DISCUSSION: Comfortable and fast gait speeds demonstrated excellent reliability
between sessions (ICC = 0.92 and 0.96, respectively). The corresponding MDCs were
0.22 and 0.23 m/s, respectively. The test-retest reliability for step frequency
was moderate for comfortable gait speed and good for fast gait speeds (ICC = 0.73
and 0.82, respectively). The corresponding MDCs were 15.1 and 17.4 steps per
minute for comfortable and fast step frequency, respectively. CONCLUSIONS: Under
both comfortable and fast conditions, measurements of gait speed and step
frequency during the 10MWT are reliable between sessions in individuals with PD.
PMID- 26428903
TI - High-Velocity Quadriceps Exercises Compared to Slow-Velocity Quadriceps Exercises
Following Total Knee Arthroplasty: A Randomized Clinical Study.
AB - BACKGROUND AND PURPOSE: Despite improvement in pain and perceived function in
older adults following total knee arthroplasty (TKA), objective outcome measures
of muscular impairment and ambulatory function demonstrate significant deficits.
Evidence suggests that quadriceps power may play a greater role in ambulatory
function than measures of strength alone following TKA. The purpose of this study
was to compare the effect of high-velocity (HV) quadriceps exercises with that of
slow-velocity (SV) quadriceps exercises on functional outcomes and quadriceps
power following TKA. METHODS: This study was a randomized clinical study
conducted in an outpatient physical therapy clinic. Twenty-one participants who
were 4 to 6 weeks post unilateral TKA were randomly assigned to an HV or SV
group. Participants performed an evidence-based standardized progressive
resistance exercise program in addition to HV quadriceps exercises or SV
quadriceps exercises. Participants attended 2 sessions per week for 8 weeks.
Before and after the 8-week exercise intervention, participants completed a
functional questionnaire, health survey, functional testing, and underwent
quadriceps strength and power testing. RESULTS: Both groups demonstrated
improvements in ambulatory outcome measures, strength, speed, and power. The HV
group demonstrated significantly greater improvements in distance walked and
quadriceps strength than the SV group. LIMITATIONS: These data should be
considered preliminary because of a small sample size. CONCLUSION: HV quadriceps
exercises may be an effective rehabilitation strategy in conjunction with a
standardized progressive resistance exercise program beginning 4 to 6 weeks after
TKA.
PMID- 26428904
TI - Long term study of deoxyribozyme administration to XT-1 mRNA promotes
corticospinal tract regeneration and improves behavioral outcome after spinal
cord injury.
AB - Spinal cord injury (SCI) affects approximately 3 million people around the world,
who are desperately awaiting treatment. The pressing need for the development of
therapeutics has spurred medical research for decades. To respond to this
pressing need, our group developed a potential therapeutic to reduce the presence
of proteoglycans at the injury site after acutely traumatizing the spinal cord of
rats. With the aid of a DNA enzyme against the mRNA of xylosyltransferase-1
(DNAXT-1as) we adjourn the glycosylation and prevent the assembly of the
proteoglycan core protein into the extracellular matrix. Hence, endogenous repair
is strengthened due to the allocation of a more growth permissive environment
around the lesion site. Here, we present data on a long term study of animals
with a dorsal hemisection treated with DNAXT-1as, DNAXT-1mb (control DNA enzyme)
or PBS via osmotic minipumps. After successful digestion of the XT-1 mRNA shown
by qPCR we observed an overall behavioral improvement of DNAXT-1as treated rats
at 8, 10 and 14 weeks after insult to the spine compared to the control animals.
This is accompanied by the growth of the cortical spinal tract (CST) in DNAXT-1as
treated animals after a 19 week survival period. Furthermore, after evaluating
the lesion size tissue-protective effects in the DNAXT-1as treated animals
compared to DNAXT-1mb and PBS treated rats are revealed. The results yield new
insights into the regeneration processes and provide confirmation to involve DNA
enzyme administration in future therapeutic strategies to medicate SCI.
PMID- 26428905
TI - Reduced vesicular monoamine transport disrupts serotonin signaling but does not
cause serotonergic degeneration.
AB - We previously demonstrated that mice with reduced expression of the vesicular
monoamine transporter 2 (VMAT2 LO) undergo age-related degeneration of the
catecholamine-producing neurons of the substantia nigra pars compacta and locus
ceruleus and exhibit motor disturbances and depressive-like behavior. In this
work, we investigated the effects of reduced vesicular transport on the function
and viability of serotonin neurons in these mice. Adult (4-6 months of age),
VMAT2 LO mice exhibit dramatically reduced (90%) serotonin release capacity, as
measured by fast scan cyclic voltammetry. We observed changes in serotonin
receptor responsivity in in vivo pharmacological assays. Aged (months) VMAT2 LO
mice exhibited abolished 5-HT1A autoreceptor sensitivity, as determined by 8-OH
DPAT (0.1 mg/kg) induction of hypothermia. When challenged with the 5HT2 agonist,
2,5-dimethoxy-4-iodoamphetamine (1 mg/kg), VMAT2 LO mice exhibited a marked
increase (50%) in head twitch responses. We observed sparing of serotonergic
terminals in aged mice (18-24 months) throughout the forebrain by SERT
immunohistochemistry and [(3)H]-paroxetine binding in striatal homogenates of
aged VMAT2 LO mice. In contrast to their loss of catecholamine neurons of the
substantia nigra and locus ceruleus, aged VMAT2 LO mice do not exhibit a change
in the number of serotonergic (TPH2+) neurons within the dorsal raphe, as
measured by unbiased stereology at 26-30 months. Collectively, these data
indicate that reduced vesicular monoamine transport significantly disrupts
serotonergic signaling, but does not drive degeneration of serotonin neurons.
PMID- 26428906
TI - Cognitive impairments may mimic delusions.
AB - Delusions are often recognized as key to the concept of psychosis. What is
delusion is one of the basic questions of psychopathology. The common denominator
of definitions of delusions is the divergence between the strong conviction in
the delusional belief and superior evidences to the contrary which are
continually ignored. An implicit, sustainably unspoken assumption is that the
person with delusional belief has cognitive capacities to process the (counter
)arguments relevant to their delusion. However, individual's cognitive capacities
are not being emphasized when delusions are evaluated. Moreover, the impact of
cognitive decline on formation of delusions is neglected, both in theory and
practice. We elaborate that cognitive deficits may facilitate, oppose, or mimic
delusions. We focus on the last, which can lead to diagnosing as delusion what
could be explained by cognitive decline and better called pseudo-delusion. The
risk is significant when cognition is impaired, as in demented people; an issue
which has not yet been debated. True delusions are incompatible with person's
cognitive capacities, i.e., if we take into account person's cognitive status, we
still cannot understand how the person holds the strange belief with an
extraordinary conviction. Pseudo-delusions would be beliefs, thoughts or
judgments that at first seem delusional (they are false, subculturally atypical
beliefs that are strongly maintained in the face of counterargument), but lose
the essence of delusions after we take cognitive impairment into account. Pseudo
delusions could actually be explained or understood by person's cognitive
impairments, they "fit into" them. The reported reality-based contents of
delusions in the elderly, poor response to antipsychotics and lack of association
with early or family history of psychiatric disorders could in part be accounted
for by the bias of misdiagnosing the cognitive impairment as the delusion. Not
recognizing that the cognitive impairment underlies formation of pseudo-delusions
and misdiagnosing it as delusions may lead to focusing on antipsychotic
treatment, instead on treatment of the underlying cognitive deficit.
PMID- 26428907
TI - Age-related differences on low back pain and postural control during one-leg
stance: a case-control study.
AB - BACKGROUND AND PURPOSE: The prevalence of chronic low back pain (CLBP) is higher
in older than in younger adults and is associated with poor postural control and
falls. The objective of this study was to compare the postural control of younger
and older subjects with and without CLBP during a one-leg stance. METHODS: Twenty
subjects with and 20 subjects without nonspecific CLBP participated in the study.
Each group contained 10 younger (50% males; mean age: 31 years) and 10 older
adults (50% males; mean age 71 years). The subjects performed three 30-s trials
of a one-leg stance on a force platform. Balance parameters were computed to
quantify postural control, including center of pressure (COP) area, mean
velocity, and mean frequency in the anteroposterior and mediolateral directions.
RESULTS: Participants with CLBP presented significantly poorer balance (P < 0.05)
than participants without CLBP. The effect size was large for younger adults (d =
1.44) and small for older adults (d = 0.40). Older adults with CLBP presented
poorer balance than younger adults with CLBP (large effect size, d = 1.24).
CONCLUSIONS: The findings indicate that CLBP affects the balance of both younger
and older adults, and that the age-related changes also affect balance and modify
the magnitude of CLBP effects on balance.
PMID- 26428908
TI - Fracture Rates and Lifetime Estimations of CAD/CAM All-ceramic Restorations.
AB - The gathering of clinical data on fractures of dental restorations through
prospective clinical trials is a labor- and time-consuming enterprise. Here, we
propose an unconventional approach for collecting large datasets, from which
clinical information on indirect restorations can be retrospectively analyzed.
The authors accessed the database of an industry-scale machining center in
Germany and obtained information on 34,911 computer-aided design (CAD)/computer
aided manufacturing (CAM) all-ceramic posterior restorations. The fractures of
bridges, crowns, onlays, and inlays fabricated from different all-ceramic systems
over a period of 3.5 y were reported by dentists and entered in the database.
Survival analyses and estimations of future life revealed differences in
performance among ZrO2-based restorations and lithium disilicate and leucite
reinforced glass-ceramics.
PMID- 26428909
TI - Two-dimensional motion of Brownian swimmers in linear flows.
AB - The motion of viruses and bacteria and even synthetic microswimmers can be
affected by thermal fluctuations and by external flows. In this work, we study
the effect of linear external flows and thermal fluctuations on the diffusion of
those swimmers modeled as spherical active (self-propelled) particles moving in
two dimensions. General formulae for their mean-square displacement under a
general linear flow are presented. We also provide, at short and long times,
explicit expressions for the mean-square displacement of a swimmer immersed in
three canonical flows, namely, solid-body rotation, shear and extensional flows.
These expressions can now be used to estimate the effect of external flows on the
displacement of Brownian microswimmers. Finally, our theoretical results are
validated by using Brownian dynamics simulations.
PMID- 26428910
TI - psiTurk: An open-source framework for conducting replicable behavioral
experiments online.
AB - Online data collection has begun to revolutionize the behavioral sciences.
However, conducting carefully controlled behavioral experiments online introduces
a number of new of technical and scientific challenges. The project described in
this paper, psiTurk, is an open-source platform which helps researchers develop
experiment designs which can be conducted over the Internet. The tool primarily
interfaces with Amazon's Mechanical Turk, a popular crowd-sourcing labor market.
This paper describes the basic architecture of the system and introduces new
users to the overall goals. psiTurk aims to reduce the technical hurdles for
researchers developing online experiments while improving the transparency and
collaborative nature of the behavioral sciences.
PMID- 26428911
TI - Erratum to: Characterization of the Nencki Affective Picture System by discrete
emotional categories (NAPS BE).
PMID- 26428912
TI - The what, why, and how of born-open data.
AB - Although many researchers agree that scientific data should be open to scrutiny
to ferret out poor analyses and outright fraud, most raw data sets are not
available on demand. There are many reasons researchers do not open their data,
and one is technical. It is often time consuming to prepare and archive data. In
response, my laboratory has automated the process such that our data are archived
the night they are created without any human approval or action. All data are
versioned, logged, time stamped, and uploaded including aborted runs and data
from pilot subjects. The archive is GitHub, github.com, the world's largest
collection of open-source materials. Data archived in this manner are called born
open. In this paper, I discuss the benefits of born-open data and provide a brief
technical overview of the process. I also address some of the common concerns
about opening data before publication.
PMID- 26428913
TI - The revised NEUROGES-ELAN system: An objective and reliable interdisciplinary
analysis tool for nonverbal behavior and gesture.
AB - As visual media spread to all domains of public and scientific life, nonverbal
behavior is taking its place as an important form of communication alongside the
written and spoken word. An objective and reliable method of analysis for hand
movement behavior and gesture is therefore currently required in various
scientific disciplines, including psychology, medicine, linguistics,
anthropology, sociology, and computer science. However, no adequate common
methodological standards have been developed thus far. Many behavioral gesture
coding systems lack objectivity and reliability, and automated methods that
register specific movement parameters often fail to show validity with regard to
psychological and social functions. To address these deficits, we have combined
two methods, an elaborated behavioral coding system and an annotation tool for
video and audio data. The NEUROGES-ELAN system is an effective and user-friendly
research tool for the analysis of hand movement behavior, including gesture, self
touch, shifts, and actions. Since its first publication in 2009 in Behavior
Research Methods, the tool has been used in interdisciplinary research projects
to analyze a total of 467 individuals from different cultures, including subjects
with mental disease and brain damage. Partly on the basis of new insights from
these studies, the system has been revised methodologically and conceptually. The
article presents the revised version of the system, including a detailed study of
reliability. The improved reproducibility of the revised version makes NEUROGES
ELAN a suitable system for basic empirical research into the relation between
hand movement behavior and gesture and cognitive, emotional, and interactive
processes and for the development of automated movement behavior recognition
methods.
PMID- 26428914
TI - Daily television viewing time and associated risk of obesity among U.S. preschool
aged children: An analysis of NHANES 2009-2012.
PMID- 26428916
TI - Gene expression profiling of DMU-212-induced apoptosis and anti-angiogenesis in
vascular endothelial cells.
AB - CONTEXT: trans-3,4,5,4'-Tetramethoxystilbene (DMU-212), an derivative of
resveratrol, shows strong antiproliferative activities against many cancer cells.
In our previous study, we demonstrated that DMU-212 possesses potent proapoptosis
and antiangiogenesis effects on vascular endothelial cells (VECs), which made it
a promising agent for the treatment of angiogenesis-related diseases. OBJECTIVE:
We studied the gene expression profile of DMU-212-treated VECs to gain further
insight into the mechanisms by which DMU-212 exerts its potent pro-apoptosis and
antiangiogenesis effects. MATERIALS AND METHODS: The potential changes in the
gene expression of VECs incubated with DMU-212 were identified and analyzed using
the Affymetrix HG-U133 Plus 1.0 array. In addition, the gene expression profile
was validated by quantitative real-time PCR (qRT-PCR) analysis for seven of those
altered genes. RESULTS AND CONCLUSION: DMU-212 was found to regulate a diverse
range of genes, including cytokines (IL8, selectin E, MPZL2, EGR1, CCL20, ITGB8,
CXCL1, VCAM1, KITLG, and AREG), transport proteins (TRPC4, SLC41A2, SLC17A5, and
CREB5), metabolism (CYP1B1, CYP1A1, PDK4, CSNK1G1, MVK, TCEB3C, and CDKN3),
enzymes (RAB23, SPHK1, CHSY3, PLAU, PLA2G4C, and MMP10), and genes involved in
signal transduction (TMEM217, DUSP8, and SPRY4), chromosome organization
(HIST1H2BH and GEM), cell migration and angiogenesis (ERRFI1, HBEGF, and NEDD9),
and apoptosis (TNFSF15, TNFRSF9, CD274, BCL2L11, BIRC3, TNFAIP3, and TIFA), as
well as other genes with unknown function (PGM5P2, SNORD1142, LOC151760, KRTAP5
2, C1orf110, SNORA14A, MIR31, C2CD4B, SCARNA4, C2orf66, SC4MOL, LOC644714, and
LOC283392). This is the first application of microarray technique to investigate
and analyze the profile of genes regulated by DMU-212 in VECs. Our results lead
to an increased understanding of the signaling pathways involved in DMU-212
induced apoptosis and antiangiogenesis.
PMID- 26428915
TI - Analysis of knockout mutants reveals non-redundant functions of poly(ADP
ribose)polymerase isoforms in Arabidopsis.
AB - The enzyme poly(ADP-ribose)polymerase (PARP) has a dual function being involved
both in the poly(ADP-ribosyl)ation and being a constituent of the NAD(+) salvage
pathway. To date most studies, both in plant and non-plant systems, have focused
on the signaling role of PARP in poly(ADP-ribosyl)ation rather than any role that
can be ascribed to its metabolic function. In order to address this question we
here used a combination of expression, transcript and protein localization
studies of all three PARP isoforms of Arabidopsis alongside physiological
analysis of the corresponding mutants. Our analyses indicated that whilst all
isoforms of PARP were localized to the nucleus they are also present in non
nuclear locations with parp1 and parp3 also localised in the cytosol, and parp2
also present in the mitochondria. We next isolated and characterized insertional
knockout mutants of all three isoforms confirming a complete knockout in the full
length transcript levels of the target genes as well as a reduced total leaf NAD
hydrolase activity in the two isoforms (PARP1, PARP2) that are highly expressed
in leaves. Physiological evaluation of the mutant lines revealed that they
displayed distinctive metabolic and root growth characteristics albeit unaltered
leaf morphology under optimal growth conditions. We therefore conclude that the
PARP isoforms play non-redundant non-nuclear metabolic roles and that their
function is highly important in rapidly growing tissues such as the shoot apical
meristem, roots and seeds.
PMID- 26428917
TI - Sphingomonas parvus sp. nov. isolated from a ginseng-cultivated soil.
AB - Strain GP20-2(T) was isolated from a soil cultivated with ginseng in Korea. The
16S rRNA gene sequence of this strain showed the highest sequence similarity with
Sphingomonas daechungensis CH15-11(T) (96.7%) and Sphingomonas sediminicola Dae
20(T) (96.2%) among the type strains. The strain GP20-2(T) was a strictly
aerobic, Gram-negative, non-motile, rod-shaped bacterium that formed very tiny
colonies, less than 0.3 mm in diameter after 10 days on R2A agar. The strain grew
at 10-35-C (optimum, 35-C), at a pH of 5.0-8.0 (optimum, pH 6.0), and in the
absence of NaCl. The DNA G+C content of strain GP20-2(T) was 67.2 mol%. It
contained ubiquinone Q-10 as the major isoprenoid quinone, and summed feature 8
(C18:1omega6c and/or C18:1omega7c, 49.8%) and C16:0 (17.0%) as the major fatty
acids. On the basis of evidence from our polyphasic taxonomic study, we concluded
that strain GP20-2(T) should be classified as a novel species of the genus
Sphingomonas, for which the name Sphingomonas parvus sp. nov. is proposed. The
type strain is GP20-2(T) (=KACC 12865(T) =DSM 100456(T)).
PMID- 26428918
TI - Illumina-based analysis of bacterial diversity related to halophytes Salicornia
europaea and Sueada aralocaspica.
AB - We used Illumina-based 16S rRNA V3 amplicon pyrosequencing to investigate the
community structure of soil bacteria from the rhizosphere surrounding Salicornia
europaea, and endophytic bacteria living in Salicornia europaea plants and Sueada
aralocaspica seeds growing at the Fukang Desert Ecosystem Observation and
Experimental Station (FDEOES) in Xinjiang Province, China, using an Illumina
genome analyzer. A total of 89.23 M effective sequences of the 16S rRNA gene V3
region were obtained from the two halophyte species. These sequences revealed a
number of operational taxonomic units (OTUs) in the halophytes. There were
between 22-2,206 OTUs in the halophyte plant sample, at the 3% cutoff level, and
a sequencing depth of 30,000 sequences. We identified 25 different phyla, 39
classes and 141 genera from the resulting 134,435 sequences. The most dominant
phylum in all the samples was Proteobacteria (41.61%-99.26%; average, 43.30%).
The other large phyla were Firmicutes (0%- 7.19%; average, 1.15%), Bacteroidetes
(0%-1.64%; average, 0.44%) and Actinobacteria (0%-0.46%; average, 0.24%). This
result suggested that the diversity of bacteria is abundant in the rhizosphere
soil, while the diversity of bacteria was poor within Salicornia europaea plant
samples. To the extent of our knowledge, this study is the first to characterize
and compare the endophytic bacteria found within different halophytic plant
species roots using PCR-based Illumina pyrosequencing method.
PMID- 26428919
TI - Performance of PCR-reverse blot hybridization assay for detection of rifampicin
resistant Mycobacterium leprae.
AB - Drug resistance in Mycobacterium leprae is a significant problem in countries
where leprosy is endemic. A sensitive, specific, and high-throughput reverse blot
hybridization assay (REBA) for the detection of genotypic resistance to
rifampicin (RIF) was designed and evaluated. It has been shown that resistance to
RIF in M. leprae involves mutations in the rpoB gene encoding the -subunit of the
RNA polymerase. The PCR-REBA simultaneously detects both 6 wild-type regions and
5 different mutations (507 AGC, 513 GTG, 516 TAT, 531 ATG, and 531 TTC) including
the most prevalent mutations at positions 507 and 531. Thirty-one clinical
isolates provided by Korea Institute of Hansen-s Disease were analyzed by PCR
REBA with RIF resistance of rpoB gene. As a result, missense mutations at codons
507 AGC and 531 ATG with 2-nucleotide substitutions were found in one sample, and
a missense mutation at codon 516 TAT and DeltaWT6 (deletion of 530-534) was found
in another sample. These cases were confirmed by DNA sequence analysis. This
rapid, simple, and highly sensitive assay provides a practical alternative to
sequencing for genotypic evaluation of RIF resistance in M. leprae.
PMID- 26428920
TI - Antifungal activity of violacein purified from a novel strain of Chromobacterium
sp. NIIST (MTCC 5522).
AB - A novel strain of Chromobacterium sp. NIIST (MTCC 5522) producing high level of
purple blue bioactive compound violacein was isolated from clay mine acidic
sediment. During 24 h aerobic incubation in modified Luria Bertani medium, around
0.6 g crude violacein was produced per gram of dry weight biomass. An inexpensive
method for preparing crystalline, pure violacein from crude pigment was developed
(12.8 mg violacein/L) and the pure compound was characterized by different
spectrometric methods. The violacein prepared was found effective against a
number of plant and human pathogenic fungi and yeast species such as Cryptococcus
gastricus, Trichophyton rubrum, Fusarium oxysporum, Rhizoctonia solani,
Aspergillus flavus, Penicillium expansum, and Candida albicans. The best activity
was recorded against Trichophyton rubrum (2 -g/ml), a human pathogen responsible
for causing athlete-s foot infection. This is the first report of antifungal
activity of purified violacein against pathogenic fungi and yeast.
PMID- 26428921
TI - Relationships between the use of Embden Meyerhof pathway (EMP) or Phosphoketolase
pathway (PKP) and lactate production capabilities of diverse Lactobacillus
reuteri strains.
AB - The aims of this study is to compare the growth and glucose metabolism of three
Lactobacillus reuteri strains (i.e. DSM 20016, DSM 17938, and ATCC 53608) which
are lactic acid bacteria of interest used for diverse applications such as
probiotics implying the production of biomass, or for the production of valuable
chemicals (3-hydroxypropionaldehyde, 3-hydroxypropionic acid, 1,3-propanediol).
However, the physiological diversity inside the species, even for basic
metabolisms, like its capacity of acidification or glucose metabolism, has not
been studied yet. In the present work, the growth and metabolism of three strains
representative of the species diversity have been studied in batch mode. The
strains were compared through characterization of growth kinetics and evaluation
of acidification kinetics, substrate consumption and product formation. The
results showed significant differences between the three strains which may be
explained, at least in part, by variations in the distribution of carbon source
between two glycolytic pathways during the bacterial growth: the phosphoketolase
or heterolactic pathway (PKP) and the Embden-Meyerhof pathway (EMP). It was also
shown that, in the context of obtaining a large amount of biomass, DSM 20016 and
DSM 17938 strains were the most effective in terms of growth kinetics. The DSM
17938 strain, which shows the more significant metabolic shift from EMP to PKP
when the pH decreases, is more effective for lactate production.
PMID- 26428922
TI - Structural basis for the ATP-independent proteolytic activity of LonB proteases
and reclassification of their AAA+ modules.
AB - Lon proteases degrade defective or denature proteins as well as some folded
proteins for the control of cellular protein quality. There are two types of Lon
proteases, LonA and LonB. Each consists of two functional components: a protease
component and an ATPase associated with various cellular activities (AAA+
module). Here, we report the 2.03 -resolution crystal structure of the isolated
AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB).
The iAAA+ module, having no bound nucleotide, adopts a conformation virtually
identical to the ADP-bound conformation of AAA+ modules in the hexameric
structure of TonLonB; this provides insights into the ATP-independent proteolytic
activity observed in a LonB protease. Structural comparison of AAA+ modules
between LonA and LonB revealed that the AAA+ modules of Lon proteases are
separated into two distinct clades depending on their structural features. The
AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined
for the first time in this study, while the AAA+ module of LonA is a member of
the HCLR clade.
PMID- 26428923
TI - Regulation of HBV-specific CD8(+) T cell-mediated inflammation is diversified in
different clinical presentations of HBV infection.
AB - Chronic HBV infection is the leading cause of liver cirrhosis and hepatic cancer,
but the individual responses toward HBV infection are highly variable, ranging
from asymptomatic to chronic active hepatitis B inflammation. In this study, we
hypothesized that the different individual responses to HBV infection was
associated with differences in HBV-specific CD8(+) T cell-mediated inflammation
and cytotoxicity. Blood samples were collected from subjects with asymptomatic
HBV-infection, subjects undergoing active chronic HBV flares (active CHB), and
subjects with HBV-infected hepatocellular carcinoma (HBV-HCC). By tetramer
staining, we found that all three groups had similar frequencies of HBVspecific
CD8(+) T cells. However, after HBV peptide stimulation, the HBV-specific CD8(+) T
cells in asymptomatic subjects had significantly stronger interferon gamma (IFN
gamma), tumor necrosis factor alpha (TNF-alpha), and CD107a expression than those
in active CHB and HBV-HCC patients. Examination of surface marker expression
revealed that the PD-1(-)Tim-3(-) double-negative cell population was the main
contributor to HBV-specific inflammation. In active CHB patients and HBV-HCC
patients, however, the frequencies of activated PD-1(-)Tim-3(-) cells were
significantly reduced. Moreover, the serum HBV DNA titer was not correlated with
the frequencies of HBV-specific CD8(+) T cells but was inversely correlated with
the frequencies of IFN-g-expressing and CD107a-express cells in response to HBV
stimulation. Together, our data demonstrated that the status of HBVspecific
CD8(+) T cell exhaustion was associated with different clinical outcomes of
chronic HBV infection.
PMID- 26428924
TI - The hrp pathogenicity island of Pseudomonas syringae pv. tomato DC3000 is induced
by plant phenolic acids.
AB - Plants produce a wide array of antimicrobial compounds, such as phenolic
compounds, to combat microbial pathogens. The hrp PAI is one of the major
virulence factors in the plant pathogen, Pseudomonas syringae. A major role of
hrp PAI is to disable the plant defense system during bacterial invasion. We
examined the influence of phenolic compounds on hrp PAI gene expression at low
and high concentrations. There was approximately 2.5 times more hrpA and hrpZ
mRNA in PtoDC3000 that was grown in minimal media (MM) supplemented with 10 -M of
ortho-coumaric acid than in PtoDC3000 grown in MM alone. On the other hand, a
significantly lower amount of hrpA mRNA was observed in bacteria grown in MM
supplemented with a high concentration of phenolic compounds. To determine the
regulation pathway for hrp PAI gene expression, we performed qRTPCR using gacS,
gacA, and hrpS deletion mutants.
PMID- 26428926
TI - Erratum to: Identification of the Vibrio vulnificus htpG gene and its influence
on cold shock recovery.
PMID- 26428925
TI - Characterization of the rapamycin-inducible EBV LMP1 activation system.
AB - Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) is required
for EBV-mediated B lymphocyte transformation into proliferating lymphoblastoid
cell lines (LCL). LMP1 oligomerizes spontaneously in membrane lipid rafts via its
transmembrane domain and constitutively activates signal transduction pathways,
including NF-kappaB, p38 Mitogen-Activated Protein Kinase (MAPK), and c-Jun N
terminal Kinase (JNK). Since LMP1 mimics the tumor necrosis factor receptor
(TNFR), CD40, it may be effectively utilized to study the effects of constitutive
activation of signal transduction pathways on cellular physiology. On the other
hand, LMP1 presents a disadvantage in terms of determining the sequential events
and factors involved in signaling pathways. A CD40-LMP1 chimeric molecule has
been generated to overcome this limitation but does not represent the authentic
and physiological nature of LMP1. In the current study, a ligand-dependent
activation system for LMP1 using rapamycin-inducible dimerization was generated
to delineate the LMP1 signaling pathway.
PMID- 26428927
TI - Platelet Larger Cell Ratio and High-on Treatment Platelet Reactivity During Dual
Antiplatelet Therapy.
AB - BACKGROUND: Low response to antiplatelet agents has been associated to an
increased risk of thrombotic complications and recurrent ischemic events.
Platelet size has been proposed as a potential marker of platelet reactivity.
Therefore, the aim of the present study was to evaluate the impact of platelet
Larger Cell Ratio (p-LCR) on platelet aggregation and the prevalence of residual
high-on treatment platelet reactivity (HRPR) in patients receiving dual
antiplatelet therapy (DAPT) after a recent acute coronary syndrome or coronary
revascularization. METHODS: Patients treated with DAPT (ASA and clopidogrel or
ticagrelor) were scheduled for platelet function assessment at 30-90 days post
discharge. HRPR was considered for ASPI test >862 AU*min (for ASA) or ADP test
values >=417 AU*min (for ADP-antagonists) using impedance aggregometry. RESULTS:
Our population consisted of 530 patients receiving DAPT, who were divided in
tertiles according to values of p-LCR (< 27.6; 27.6-34.7; >=34.7 l). p-LCR was
related with use of beta-blockers (p = 0.02) and statins (p = 0.002), and
inversely with acute presentation (p = 0.05). Higher platelet count (p < 0.001)
and haemoglobin levels (p = 0.001) were observed in higher p-LCR tertiles. The
prevalence of HRPR for ASA was low and not significantly different across
tertiles of p-LCR (1.1 vs 1.1 vs 1.7%, p = 0.66; adjusted OR[95%CI] = 1.68[0.66
4.29], p = 0.27). Moreover, p-LCR did not influence the occurrence of HRPR for
ADP-antagonists (24.4% vs 20.9% vs 25.6 %%, p = 0.80, adjusted OR[95%CI] =
0.88[0.67-1.17], p = 0.38) and similar results were obtained when considering
separately patients receiving clopidogrel (adjusted OR[95%CI] = 1.21[0.86-1.69],
p = 0.29) or ticagrelor (adjusted OR[95%CI] = 1.17[0.69-2], p = 0.56).
CONCLUSION: In patients receiving DAPT for coronary artery disease, p-LCR does
not impact platelet reactivity. Larger platelets did not influence the prevalence
of high-on treatment platelet reactivity with the antiplatelet agents ASA,
clopidogrel or ticagrelor.
PMID- 26428928
TI - Rapid Microwave-Assisted Solvothermal Synthesis of Non-Olivine Cmcm Polymorphs of
LiMPO4 (M = Mn, Fe, Co, and Ni) at Low Temperature and Pressure.
AB - Lithium transition-metal phosphates, LiMPO4 (M = Mn, Fe, Co, and Ni), have
attracted significant research interest over the past two decades as an important
class of lithium ion battery cathode materials. However, almost all of the
investigations thus far have focused on the olivine polymorph that exists in the
orthorhombic Pnma space group. In this study, a distinct orthorhombic but non
olivine polymorph of LiMPO4, described by a Cmcm space group symmetry, has been
synthesized with M = Mn, Fe, Co, and Ni. Of these, LiMnPO4 in the Cmcm space
group is reported for the first time. A rapid microwave-assisted solvothermal (MW
ST) heating process with tetraethylene glycol (TEG) as the solvent and transition
metal oxalates as precursors facilitates the synthesis of these materials. The
peak reaction temperatures and pressures were below 300 degrees C and 30 bar,
respectively, which are several orders of magnitude lower than those of the
previously reported high-pressure (gigapascals) method. X-ray diffraction (XRD)
confirms the crystal structure with the Cmcm space group, and scanning electron
micrographs indicate a submicrometer thin platelet-like morphology. The synthesis
process conditions have been optimized to obtain impurity-free samples with the
correct stoichiometry, as characterized by XRD and inductively coupled plasma
optical emission spectroscopy (ICP-OES). Upon heat treatment to higher
temperatures, an irreversible transformation of the metastable Cmcm polymorphs
into olivine is observed by XRD and Fourier transform infrared spectroscopy.
Although the electrochemical activity of these polymorphs as lithium ion cathodes
turns out to be poor, the facile synthesis under mild conditions has permitted
easy access to these materials in a nanomorphology, some of which were not even
possible before.
PMID- 26428929
TI - Connectivity mapping uncovers small molecules that modulate neurodegeneration in
Huntington's disease models.
AB - Huntington's disease (HD) is a genetic disease caused by a CAG trinucleotide
repeat expansion encoding a polyglutamine tract in the huntingtin (HTT) protein,
ultimately leading to neuronal loss and consequent cognitive decline and death.
As no treatments for HD currently exist, several chemical screens have been
performed using cell-based models of mutant HTT toxicity. These screens measured
single disease-related endpoints, such as cell death, but had low 'hit rates' and
limited dimensionality for therapeutic detection. Here, we have employed gene
expression microarray analysis of HD samples--a snapshot of the expression of
25,000 genes--to define a gene expression signature for HD from publically
available data. We used this information to mine a database for chemicals
positively and negatively correlated to the HD gene expression signature using
the Connectivity Map, a tool for comparing large sets of gene expression
patterns. Chemicals with negatively correlated expression profiles were highly
enriched for protective characteristics against mutant HTT fragment toxicity in
in vitro and in vivo models. This study demonstrates the potential of using gene
expression to mine chemical activity, guide chemical screening, and detect
potential novel therapeutic compounds. KEY MESSAGES: Single-endpoint chemical
screens have low therapeutic discovery hit-rates. In the context of HD, we guided
a chemical screen using gene expression data. The resulting chemicals were highly
enriched for suppressors of mutant HTT fragment toxicity. This study provides a
proof of concept for wider usage in all chemical screening.
PMID- 26428931
TI - Laser epilation prior to pilonidal sinus surgery.
PMID- 26428930
TI - Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide
vaccine efficacy in castration-resistant prostate cancer patients.
AB - Personalized peptide vaccination (PPV) is an attractive approach to cancer
immunotherapy with strong immune-boosting effects conferring significant clinical
benefit. However, as with most therapeutic agents, there is a difference in
clinical efficacy among patients receiving PPV. Therefore, a useful biomarker is
urgently needed for prognosticating clinical outcomes to preselect patients who
would benefit the most from PPV. In this retrospective study, to detect a
molecular prognosticator of clinical outcomes for PPV, we analyzed whole-genome
gene expression profiles of peripheral blood mononuclear cells (PBMCs) in
castration-resistant prostate cancer (CRPC) patients before administration of
PPV. Cox regression analysis revealed that mRNA expression of myeloperoxidase,
haptoglobin, and neutrophil elastase was significantly associated with overall
survival (OS) among vaccinated CRPC patients (adjusted P < 0.01). By promoter
sequence analysis of these three genes, we found that rs5472 of haptoglobin (HP),
an acute-phase plasma glycoprotein, was strongly correlated to OS of vaccinated
CRPC patients (P = 0.0047, hazard ratio 0.47; 95 % confidence interval 0.28
0.80). Furthermore, both HP mRNA expression in PBMCs and protein level in plasma
of CRPC patients before administration of PPV exhibited rs5472 dependence (P <
0.001 for mRNA expression and P < 0.05 for protein level). Our findings suggest
that rs5472 may play an important role in the immune response to PPV via
regulation of HP. Thus, we concluded that rs5472 is a potential prognostic
biomarker for PPV.
PMID- 26428932
TI - Integrated cooling-vacuum-assisted 1540-nm erbium:glass laser is effective in
treating mild-to-moderate acne vulgaris.
AB - Acne treatment by a mid-infrared laser may be unsatisfactory due to deeply
situated acne-affected sebaceous glands which serve as its target. Skin
manipulation by vacuum and contact cooling may improve laser-skin interaction,
reduce pain sensation, and increase overall safety and efficacy. To evaluate the
safety and efficacy of acne treatment using an integrated cooling-vacuum-assisted
1540-nm erbium:glass laser, a prospective interventional study was conducted. It
included 12 patients (seven men and five women) suffering from mild-to-moderate
acne vulgaris. The device utilizes a mid-infrared 1540-nm laser (Alma Lasers Ltd.
Caesarea, Israel), which is integrated with combined cooling-vacuum-assisted
technology. An acne lesion is initially manipulated upon contact by a vacuum
cooling-assisted tip, followed by three to four stacked laser pulses (500-600 mJ,
4 mm spot size, and frequency of 2 Hz). Patients underwent four to six treatment
sessions with a 2-week interval and were followed-up 1 and 3 months after the
last treatment. Clinical photographs were taken by high-resolution digital camera
before and after treatment. Clinical evaluation was performed by two independent
dermatologists, and results were graded on a scale of 0 (exacerbation) to 4 (76
100 % improvement). Patients' and physicians' satisfaction was also recorded.
Pain perception and adverse effects were evaluated as well. All patients
demonstrated a moderate to significant improvement (average score of 3.6 and 2.0
within 1 and 3 months, respectively, following last treatment session). No side
effects, besides a transient erythema, were observed. Cooling-vacuum-assisted
1540-nm laser is safe and effective for the treatment of acne vulgaris.
PMID- 26428934
TI - Once Daily Self-Monitoring of Blood Glucose (SMBG) Improves Glycemic Control in
Oral Hypoglycemic Agents (OHA)-Treated Diabetes: SMBG-OHA Follow-Up Study.
AB - BACKGROUND: The aim of this study was to compare glycemic control between SMBG
continued and -discontinued subjects with type 2 diabetes in the SMBG-OHA study.
METHOD: Of the 96 subjects from the SMBG-OHA study, 59 were recruited for the 24
week, comparison follow-up study. The study outcomes were the differences in
change in HbA1c levels at 24 weeks between the 2 groups, and change in SMBG
frequency in SMBG-continued subjects. RESULTS: Although health insurance does not
cover the cost of SMBG, 22.0% of subjects continued SMBG of their own will after
the SMBG-OHA study was completed. HbA1c levels were maintained from 6.81 +/-
0.55% to 6.64 +/- 0.53% in SMBG-continued subjects. Conversely, HbA1c levels were
increased from 7.18 +/- 0.63% to 7.48 +/- 0.84% in SMBG-discontinued subjects.
HbA1c levels were significantly different by 0.83 +/- 0.25% (95% CI: -1.33 to
0.36). The difference in change in HbA1c between the groups was -0.46% (95% CI:
0.78 to -0.15). SMBG frequency was decreased from 2.02 +/- 1.06 to 1.53 +/- 0.86
times a day. CONCLUSIONS: HbA1c levels were maintained in SMBG-continued subjects
but increased in SMBG-discontinued subjects. The study implied that almost once
daily SMBG is helpful to maintain glycemic control in non-insulin-treated type 2
diabetes.
PMID- 26428935
TI - Accuracy Evaluation of an Integrated Blood Glucose Monitoring System With
Improved Test Cassettes Following ISO 15197:2013.
PMID- 26428933
TI - Exercise and the Development of the Artificial Pancreas: One of the More
Difficult Series of Hurdles.
AB - Regular physical activity (PA) promotes numerous health benefits for people
living with type 1 diabetes (T1D). However, PA also complicates blood glucose
control. Factors affecting blood glucose fluctuations during PA include activity
type, intensity and duration as well as the amount of insulin and food in the
body at the time of the activity. To maintain equilibrium with blood glucose
concentrations during PA, the rate of glucose appearance (Ra) to disappearance
(Rd) in the bloodstream must be balanced. In nondiabetics, there is a rise in
glucagon and a reduction in insulin release at the onset of mild to moderate
aerobic PA. During intense aerobic -anaerobic work, insulin release first
decreases and then rises rapidly in early recovery to offset a more dramatic
increase in counterregulatory hormones and metabolites. An "exercise smart"
artificial pancreas (AP) must be capable of sensing glucose and perhaps other
physiological responses to various types and intensities of PA. The emergence of
this new technology may benefit active persons with T1D who are prone to hypo and
hyperglycemia.
PMID- 26428936
TI - Analytical and Biological Characterization of a Noninnovator Insulin Glargine and
the Originator Drug Product.
PMID- 26428937
TI - Changes in dynamics of the glass-forming pharmaceutical nifedipine in binary
mixtures with octaacetylmaltose.
AB - Some molecular glass-formers can crystallize in the glassy state, some of which
are van der Waals molecules and some are pharmaceuticals. The molecular mechanism
responsible for this glass-to-crystal mode of crystallization is of interest to
the glass transition research community as well as to the pharmaceutical industry
because the effect is detrimental to stability of amorphous form of the drugs
stored below the glass transition temperature. Two prominent models have been
proposed for the molecular mechanism. In the homogeneous nucleation-based
crystallization model, the molecular mechanism is the secondary relaxation, and
the other model assumes that the molecular process responsible for crystal growth
in the glassy state is from the local molecular motions. Crystal growth requires
motion of the entire molecule, and in the glassy state the only such local
molecular motion is engendered by the secondary relaxation of the Johari
Goldstein (JG) kind. While the JG secondary relaxation is the crux in the two
models of glass-to-crystal growth, it has not been found in the glassy state of
the pharmaceuticals studied so far. The examples include 5-methyl-2-[(2
nitrophenyl)amino]-3-thiophenecarbonitrile (ROY), indomethacin (IMC) and
nifedipine (NIF). In the absence of any evidence of the JG secondary relaxation,
the conundrum is that the two models of glass-to-crystal growth cannot be
validated. It turns out these pharmaceuticals all have structural alpha
relaxations with narrow frequency dispersion. Empirically, glass-formers with
narrow alpha-dispersion have JG secondary relaxation with weak relaxation
strength, not well separated from the alpha-relaxation, and hence cannot be
resolved. Theoretically, the narrow width of the alpha-dispersion is due to weak
intermolecular coupling. In this article we enhance the intermolecular coupling
of NIF by mixing with octaacetylmaltose to enhance the intermolecular coupling of
NIF. In this way we have successfully resolved the JG secondary relaxation in the
dielectric loss spectra of the NIF component in the glassy state, and validated
the two models of glass-to-crystal growth.
PMID- 26428938
TI - Fatty acids for controlled release applications: A comparison between prilling
and solid lipid extrusion as manufacturing techniques.
AB - The aim of the present study was to evaluate the solid state characteristics,
drug release and stability of fatty acid-based formulations after processing via
prilling and solid lipid extrusion. Myristic acid (MA), stearic acid (SA) and
behenic acid (BA) were used as matrix formers combined with metoprolol tartrate
(MPT) as model drug. The prilling process allowed complete dissolution of MPT in
the molten fatty acid phase, generating semi-crystalline MPT and the formation of
hydrogen bonds between drug and fatty acids in the solid prills. In contrast, as
solid lipid extrusion (SLE) induced only limited melting of the fatty acids,
molecular interaction with the drug was inhibited, yielding crystalline MPT.
Although the addition of a low melting fatty acid allowed more MPT/fatty acid
interaction during extrusion, crystalline MPT was detected after processing.
Mathematical modeling revealed that the extrudates exhibited a higher apparent
drug/water mobility than prills of the same composition, probably due to
differences in the inner systems' structure. Irrespective of the processing
method, mixed fatty acid systems (e.g. MA/BA) exhibited a lower matrix porosity,
resulting in a slower drug release rate. Solid state analysis of these systems
indicated that the crystalline structure of the fatty acids was maintained after
SLE, while prilling generated a reduced MA crystallinity. Binary MPT/fatty acid
systems processed via extrusion showed better stability during storage at 40
degrees C than the corresponding prills. Although mixed fatty acid systems were
stable at 25 degrees C, stability problems were encountered during storage at 40
degrees C: a faster release was obtained from the prills, whereas drug release
from the extrudates was slower.
PMID- 26428939
TI - Selection of a mobilization regimen for multiple myeloma based on the response to
induction therapy: granulocyte-colony stimulating factor (G-CSF) alone versus
high-dose cyclophosphamide plus G-CSF.
AB - To evaluate the feasibility of selecting a mobilization regimen based on the
response to induction therapy, we retrospectively analyzed 179 multiple myeloma
patients who underwent stem cell mobilization. In comparison with patients who
achieved at least a very good partial response (VGPR) to induction therapy and
received granulocyte-colony stimulating factor (G-CSF) alone and patients who did
not achieve a VGPR and received cyclophosphamide (CY) + G-CSF, treatment-related
toxicity was greater and neutrophil engraftment was slower in the CY than the G
CSF group. The rate of requisite mobilization (>= 2.0 * 10(6)/kg) was similar in
both groups. Overall and progression-free survival was not different between
patients in the G-CSF group and patients who achieved at least VGPR and received
CY + G-CSF. In conclusion, response-adapted selection of a mobilization regimen
is appropriate. G-CSF alone should be the preferred treatment for patients who
achieved at least a VGPR to induction therapy.
PMID- 26428940
TI - Sentinel nodes in vulvar cancer: Long-term follow-up of the GROningen
INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I.
AB - OBJECTIVE: In 2008 GROINSS-V-I, the largest validation trial on the sentinel node
(SN) procedure in vulvar cancer, showed that application of the SN-procedure in
patients with early-stage vulvar cancer is safe. The current study aimed to
evaluate long-term follow-up of these patients regarding recurrences and
survival. METHODS: From 2000 until 2006 GROINSS-V-I included 377 patients with
unifocal squamous cell carcinoma of the vulva (T1, <4 cm), who underwent the SN
procedure. Only in case of SN metastases an inguinofemoral lymphadenectomy was
performed. For the present study follow-up was completed until March 2015.
RESULTS: Themedian follow-up was 105 months (range 0-179). The overall local
recurrence ratewas 27.2% at 5 years and 39.5% at 10 years after primary
treatment, while for SN-negative patients 24.6% and 36.4%, and for SN-positive
patients 33.2% and 46.4% respectively (p = 0.03). In 39/253 SN-negative patients
(15.4%) an inguinofemoral lymphadenectomy was performed, because of a local
recurrence. Isolated groin recurrence rate was 2.5% for SN-negative patients and
8.0% for SN-positive patients at 5 years. Disease-specific 10-year survival was
91% for SN-negative patients compared to 65% for SN-positive patients (p b
.0001). For all patients, 10-year disease-specific survival decreased from 90%
for patients without to 69% for patients with a local recurrence (p b .0001).
PMID- 26428941
TI - Prognostic factors of oncological and reproductive outcomes in fertility-sparing
treatment of complex atypical hyperplasia and low-grade endometrial cancer using
oral progestin in Chinese patients.
AB - OBJECTIVE: To evaluate the efficacy and fertility outcomes of progestin treatment
for complex atypical hyperplasia (CAH)/grade I endometrial cancer (G1EC) in
Chinese patients (<=40years old). METHODS: Women <=40years old who were treated
with progestin for CAH or G1EC were identified from 9 provinces of China. The
time to achieve complete response (CR) and the time from CR to recurrence or
pregnancy were censored for patients without events and were analyzed for
associations between patient and treatment characteristics. RESULTS: Thirty-two
patients were included: 13 with CAH and 19 with G1EC. Nine patients exhibited
elevated serum HbA1C before treatment. After a mean follow-up of 32.5months, the
CR rate was 84.4%. Patients who exhibited elevated HbA1C were more likely to
experience CR, while those with polycystic ovarian syndrome (PCOS) exhibited the
opposite outcome (p=0.01, 0.03). Nine of 21 patients experienced clinical
pregnancies. Eight patients underwent assisted reproductive technology (ART).
Five patients had newborn infants. Patients undergoing ART were more likely to
become pregnant (p=0.04). CONCLUSION: Oral progestin is an effective fertility
sparing treatment for women with CAH/G1EC in China. Patients with elevated HbA1C
receiving both metformin and progestin were more likely to achieve CR, whereas
those with PCOS were not. ART is a good choice for clinical pregnancy after
treatment.
PMID- 26428943
TI - Poly(N-isopropylacrylamide)-clay based hydrogels controlled by the initiating
conditions: evolution of structure and gel formation.
AB - The formation of the hydrogel poly(N-isopropylacrylamide)-clay (LAPONITE(r)) by
redox polymerization was investigated, and the main factors governing the gel
build-up were determined. The significant effect of the redox initiating system
ammonium peroxodisulfate (APS) and tetramethylethylenediamine (TEMED) on gel
formation and structure was established, making it possible to control the
structure of the gel. Moreover, the pre-reaction stage involving the quality of
the clay exfoliation in an aqueous suspension and the interaction of reaction
components with the clay play a role in controlling the polymerization and gel
structure. The molecular and phase structure evolution during polymerization was
followed in situ by the following independent techniques: Fourier transform
infrared spectroscopy (FTIR), chemorheology, small-angle X-ray scattering (SAXS)
and ultraviolet-visible spectroscopy (UV/Vis). The combination of these methods
enabled us to describe in detail particular progress stages during the gel
formation and determine the correlation of the corresponding processes on a time
and conversion scale. The mechanism of gel formation was refined based on these
experimental results.
PMID- 26428942
TI - A randomized controlled trial comparing four versus six courses of adjuvant
platinum-based chemotherapy in locally advanced cervical cancer patients
previously treated with neo-adjuvant chemotherapy plus radical surgery.
AB - OBJECTIVES. The aim of this study was to compare 4 versus 6 courses of adjuvant
chemotherapy after neoadjuvant chemotherapy plus radical surgery in terms of
overall survival (OS), disease-free survival (DFS), recurrence rate and toxicity
profile. METHODS. We randomly assigned 200 patients with IB2-IIB cervical cancer
to receive 4 (Group A) or 6 (Group B) courses of cisplatin 100 mg/mq and
paclitaxel 175 mg/mq every 21 days. RESULTS. At 4-years follow-up, the comparison
of recurrence rate (p = 1; RR = 1.005; 95% CI = 0.87 to 1.161), OS (p = 0.906)
and DFS (p = 0.825) did not show statistically significant differences between
the two groups. Data analysis showed statistically significant differences
between the two groups in term of episodes of leukopenia (p = 0.0072; RR = 1.513;
95% CI = 1.127-2.03), anemia (p = 0.048; RR = 1.188; CI = 1.012-1.395) and
febrile neutropenia (p = 0.042; RR = 1.119; 95% CI = 1.014-1.235), in favor of
Group A. As regards non-hematological toxicities, there were no statistically
significant differences in terms of gastrointestinal symptoms (p = 0.49; RR =
1.046; CI = 0.948-1.153. On the contrary, there was a statistically significant
difference regarding neurological symptoms (p=0.014; RR=1.208; CI=1.046-1.395),
that were less frequent in Group A (13%) than in Group B (28%). CONCLUSIONS.
Adjuvant treatment with 4 or 6 courses of platinum-based chemotherapy showed
similar results in terms of OS and DSF, with a favorable toxicity profile in
favor of the first regimen.
PMID- 26428944
TI - Cost and co-morbidities associated with hypoglycemic inpatients in Belgium.
AB - BACKGROUND AND OBJECTIVES: Little is known about the economic burden of
hypoglycemia in Belgium, or its related co-morbidities. This study aimed at
estimating the cost and length of stay associated with hypoglycemia-related
hospitalizations in diabetic patients in Belgium and the association between
hypoglycemia and in-hospital all-cause mortality, incidence of traumatic
fractures, depression, and cardiovascular diseases (myocardial infarction or
unstable angina), using retrospective data from 2011. METHODS: Patient data were
retrieved from the IMS Hospital Disease Database, including longitudinal (per
calendar year) information on diagnoses, procedures, and drugs prescribed in ~20%
of all Belgian hospital beds. The eligible population included all adult (<19
year) diabetic (both types) patients, further split between those with/without a
history of hypoglycemia-related hospitalizations. Diabetes, hypoglycemia, and co
morbidities of interest were identified based on International Classification of
Diseases and Related Health Problems Version 9 (ICD-9) diagnosis codes. All costs
were extrapolated to 2014 using progression in hospitalization costs since 2001.
RESULTS: A total of 43,410 diabetes-related hospitalizations were retrieved,
corresponding to 30,710 distinct patients. The average hospitalization cost was
?10,258 when hypoglycemia was documented (n = 2625), vs ?7173 in other diabetic
hospitalized patients (n = 40,785). When controlling for age and sex, a higher
mortality risk (OR = 1.59; p-value <0.001), a higher incidence of traumatic
fractures (OR = 1.25; p-value = 0.009), and a higher probability of depression
related hospitalizations (OR = 1.90; p-value <0.001) were observed in
hypoglycemic patients. A similar risk of cardiovascular event was observed in
both groups, but hypoglycemic patients were more at risk of experiencing multiple
events. CONCLUSION: Hospitalizations for hypoglycemia are expensive and
associated with an increased risk of depression and traumatic fractures as well
as increased in-hospital mortality. Interventions that can help reduce the risk
of hypoglycemia, and consequently the burden on hospitals and society, without
compromising glycemic control, will help to further improve diabetes management.
PMID- 26428945
TI - Dupilumab for the treatment of atopic dermatitis: A clinical trial review.
AB - INTRODUCTION: Current treatment options for moderate-to-severe atopic dermatitis
(AD) are limited and have potentially dangerous side effects. Dupilumab is a
novel monoclonal antibody that was recently studied in adult patients with
moderate-to-severe AD. Dupilumab inhibits interleukin-4 (IL-4) and interleukin-13
(IL-13) signaling and was previously found to be effective in asthma. Considering
that both AD and asthma are Th2 cell-mediated inflammatory processes, it is
reasonable to suspect that dupilumab would be beneficial in AD.' AREAS COVERED:
This article is a review of the one major clinical trial that assessed the
efficacy of dupilumab in patients with AD. Its goal is to provide a comparison to
the current modalities for the treatment of AD and expert insight regarding
future studies. EXPERT OPINION: The results of this study are a significant
therapeutic advancement. Dupilumab was shown to provide a mean percent change in
Eczema Area and Severity Index score of -74% +/- 3.6, in addition to,
statistically and clinically significant reductions the severity, symptomatology,
and morbidity associated with AD. However, the small sample size makes it
difficult to assess the magnitude of this effect. As a result, dupilumab will
likely be reserved for cases of severe AD unresponsive to traditional modalities.
PMID- 26428946
TI - Automated solvent system screening for the preparative countercurrent
chromatography of pharmaceutical discovery compounds.
AB - A fully automated countercurrent chromatography system has been constructed to
rapidly screen the commonly used heptane/ethyl acetate/methanol/water solvent
system series and translate the results to preparative scale separations. The
system utilizes "on-demand" preparation of the heptane/ethyl
acetate/methanol/water solvent system upper and lower phases. Elution-extrusion
countercurrent chromatography was combined with non-dynamic equilibrium injection
reducing the screening time for each heptane/ethyl acetate/methanol/water system
to 17 min. The result enabled solvent system development to be reduced to under 2
h. The countercurrent chromatography system was interfaced with a mass
spectrometer to allow selective detection of target components in crude medicinal
chemistry reaction mixtures. Mass-directed preparative countercurrent
chromatography purification was demonstrated for the first time using a synthetic
tetrazole epoxide derived from a routine medicinal chemistry support workflow.
PMID- 26428947
TI - Effect of an educational intervention on parental readiness for premature infant
discharge from the neonatal intensive care units.
AB - AIM: To examine the effect of an educational intervention on parental readiness
for premature infant discharge from neonatal intensive care units. BACKGROUND:
Low readiness for discharge can result in negative healthcare outcomes for
infants and their parents. However, few studies have examined the effect of
discharge education programmes on parental readiness for premature infant
discharge in Chinese critical care settings. DESIGN: A quasi-experimental study.
METHODS: Between October 2011-March 2012, 154 parents of premature infants were
recruited from neonatal intensive care units of two tertiary hospitals in Central
China. These parents were assigned to either the intervention or control group
based on their entry order. Parents in the intervention group received two
sessions of 60-minute discharge education along with hospital routine care;
parents in the control group only received hospital routine care. Parental
readiness for discharge and quality of discharge education were assessed on the
day of infant discharge from neonatal intensive care units. Independent samples t
test and linear regression were used to analyse the data. RESULTS: Parental
readiness for premature infant discharge was in the moderate level. Independent
samples t-test showed that both mean scores of parental discharge readiness and
discharge teaching quality from the intervention group were significantly higher
than those in the control group. Linear regression analysis showed that discharge
teaching quality explained 39.7% of the variance in parental readiness for
premature infant discharge. CONCLUSION: Discharge education can improve parental
readiness for premature infant discharge. Quality of discharge teaching can
significantly predict parental readiness for premature infant discharge.
PMID- 26428948
TI - Measuring depression in prostate cancer patients: does the scale used make a
difference?
AB - This study investigated differences in the scores, relative severity and major
depressive disorder (MDD) and subsyndromal depression status from three
standardised self-report scales for depression in prostate cancer (PCa) patients.
The Hospital Anxiety and Depression Scale Depression subscale (HADS-D), the Self
rating Depression Scale (SDS) and the Patient Health Questionnaire (PHQ-9) for
depression were administered to a sample of 138 PCa patients via mail-out self
reports in Queensland, Australia during May 2014. Despite significant
correlations between the total scores from the three scales, severity
classification differed across the three scales and there was evidence of
considerable underestimation of depression by the HADS-D compared to the PHQ-9,
and a similar tendency for the SDS. When patients were classified as fulfilling
the criteria for Subsyndromal Depression on the PHQ-9, there were statistically
significant differences in the proportion of patients who met those criteria
using the HADS-D and the SDS, with large underestimation also present for these
two scales. Scale construction and depression items included can produce
different results across scales, making inter-study comparisons difficult.
Implications for research and clinical practice are described.
PMID- 26428950
TI - Kilo-scale droplet generation in three-dimensional monolithic elastomer device
(3D MED).
AB - Droplet-based microfluidics has led to transformational new approaches in diverse
areas including materials synthesis and high-throughput biological assays.
However, the translation of droplet microfluidics technology into commercial
applications requires scale-up of droplet generation from the laboratory (<10 mL
h(-1)) to the industrial (>1 L h(-1)) scale. To address this challenge, we
develop a three-dimensional monolithic elastomer device (3D MED) for mass
production of monodisperse emulsion droplets. Using double-sided imprinting, 3D
microchannels are formed in a single elastomer piece that has 1000 parallel flow
focusing generators (k-FFGs). Compared to previous work that parallelizes droplet
generation, the 3D MED eliminates the needs for alignment and bonding of multiple
pieces and thus makes it possible to achieve the high flow rates and pressure
necessary for the kilo-scale generation of droplets. Using this approach, we
demonstrate mass production of water-in-oil (W/O) emulsion droplets at production
rates as high as 1.5 L h(-1) (>30 billion 45 MUm diameter droplets per hour),
with a coefficient of variation of droplet diameter of only 6.6%. Because of the
simplicity, robustness, and manufacturability of our 3D MED architecture, it is
well suited to bridge the gap between the continuously growing library of
promising microfluidic technologies to generate microparticles that have been
demonstrated in laboratory settings and their successful application in industry.
PMID- 26428949
TI - Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL
33-signaling pathways.
AB - Thymic stromal lymphopoietin (TSLP) and IL-33 are epithelium-derived proallergic
cytokines that contribute to allergic diseases. Although the involvement of TSLP
in allergic rhinitis (AR) is suggested, the exact role of TSLP in AR is poorly
understood. Furthermore, the relative contribution of TSLP and IL-33 in nasal
allergic responses has not been described. In this study, we examined the roles
of TSLP and IL-33 in AR by analyzing acute and chronic AR models. Acute AR mice
were intraperitoneally immunized with ragweed, then intranasally challenged with
ragweed pollen for four consecutive days. Chronic AR mice were nasally
administrated ragweed pollen on consecutive days for 3 weeks. In both models,
TSLP receptor (TSLPR)-deficient mice showed defective sneezing responses and
reduced serum ragweed-specific IgE levels compared with wild-type (WT) mice.
Analyses of bone-marrow chimeric mice demonstrated that hematopoietic cells were
responsible for defective sneezing in TSLPR-deficient mice. In addition,
FcepsilonRI(+)-cell-specific TSLPR-deficient mice showed partial but significant
reduction in sneezing responses. Of note, Th2 activation and nasal eosinophilia
were comparable between WT and TSLPR-deficient mice. ST2- and IL-33-deficient
mice showed defective Th2 activation and nasal eosinophilia to acute, but not
chronic, ragweed exposure. TSLPR and ST2 double-deficient mice showed defective
Th2 activation and nasal eosinophilia even after chronic ragweed exposure. These
results demonstrate that TSLPR signaling is critical for the early phase response
of AR by controlling the IgE-mast-cell/basophil pathway. The IL-33/ST2 pathway is
central to nasal Th2 activation during acute allergen exposure, but both TSLPR
and ST2 contribute to Th2 responses in chronically allergen-exposed mice.
PMID- 26428951
TI - Memory, Decision-Making, and the Ventromedial Prefrontal Cortex (vmPFC): The
Roles of Subcallosal and Posterior Orbitofrontal Cortices in Monitoring and
Control Processes.
AB - The ventromedial prefrontal cortex (vmPFC) prominently and separately features in
neurobiological models of decision-making (e.g., value-encoding) and of memory
(e.g., automatic veracity-monitoring). Recent decision-making models propose
value judgments that inherently comprise of second-order confidence estimates.
These demonstrate quadratic relationships with first-order judgments and are
automatically encoded in vmPFC activity. Memory studies use Quantity-Accuracy
Profiles to capture similar first-order and second-order meta-mnemonic processes,
suggesting convergence across domains. Patients with PFC damage answered general
knowledge questionnaires under 2 conditions. During forced report, they chose an
answer and rated the probability of it being correct (first-order "monitoring").
During free report, they could choose to volunteer or withhold their previous
answers (second-order "control") to maximize performance. We found quadratic
relationships between first-order and second-order meta-mnemonic processes; voxel
based lesion-symptom mapping demonstrated that vmPFC damage diminished that
relationship. Furthermore, damage to subcallosal vmPFC was specifically
associated with impaired monitoring and additional damage to posterior
orbitofrontal cortex led to deficient control. In decision-making, these regions
typically support valuation and choice, respectively. Persistent spontaneous
confabulation (false memory production) confirmed the clinical relevance of these
dissociations. Compared with patients with no confabulation history, patients who
currently confabulate were impaired on both monitoring and control, whereas
former confabulators demonstrated impaired monitoring but intact control.
PMID- 26428952
TI - Developmental Expression Patterns of KCC2 and Functionally Associated Molecules
in the Human Brain.
AB - Work on rodents demonstrated that steep upregulation of KCC2, a neuron-specific
Cl- extruder of cation-chloride cotransporter (CCC) family, commences in
supraspinal structures at around birth, leading to establishment of
hyperpolarizing GABAergic responses. We describe spatiotemporal expression
profiles of the entire CCC family in human brain. KCC2 mRNA was observed already
at 10th postconceptional week (PCW) in amygdala, cerebellum, and thalamus. KCC2
immunoreactive (KCC2-ir) neurons were abundant in subplate at 18 PCW. By 25 PCW,
numerous subplate and cortical plate neurons became KCC2-ir. The mRNA expression
profiles of alpha- and beta-isoforms of Na-K ATPase, which fuels cation-chloride
cotransport, as well of tropomyosin receptor kinase B (TrkB), which promotes
developmental upregulation of KCC2, were consistent with data from studies on
rodents about their interactions with KCC2. Thus, in human brain, expression of
KCC2 and its functionally associated proteins begins in early fetal period. Our
work facilitates translation of results on CCC functions from animal studies to
human and refutes the view that poor efficacy of anticonvulsants in the term
human neonate is attributable to the lack of KCC2. We propose that perinatally
low threshold for activation of Ca2+-dependent protease calpain renders neonates
susceptible to downregulation of KCC2 by traumatic events, such as perinatal
hypoxia ischemia.
PMID- 26428953
TI - Comments on "Some Challenges with Statistical Inference in Adaptive Designs" by
Hung, Wang, and Yang.
PMID- 26428954
TI - The Asian atopic dermatitis phenotype combines features of atopic dermatitis and
psoriasis with increased TH17 polarization.
AB - BACKGROUND: Atopic dermatitis (AD) shows very high prevalence in Asia, with a
large unmet need for effective therapeutics. Direct comparisons between European
American (EA) and Asian patients with AD are unavailable, but earlier blood
studies detected increased IL-17(+)-producing cell counts in Asian patients with
AD. OBJECTIVE: We sought to characterize the Asian AD skin phenotype and compare
it with the EA AD skin phenotype. METHODS: We performed genomic profiling (real
time PCR) and immunohistochemistry on lesional and nonlesional biopsy specimens
from 52 patients with AD (25 EAs and 27 Asians), 10 patients with psoriasis (all
EAs), and 27 healthy subjects (12 EAs and 15 Asians). RESULTS: Although disease
severity/SCORAD scores were similar between the AD groups (58.0 vs 56.7, P =
.77), greater acanthosis, higher Ki67 counts, and frequent parakeratosis were
characteristics of lesional epidermis from Asian patients with AD (P < .05). Most
(24/27) Asian patients had high IgE levels. A principal component analysis using
real-time PCR data clustered the Asian AD phenotype between the EA AD and
psoriasis phenotypes. TH2 skewing characterized both Asian and EA patients with
AD but not patients with psoriasis. Significantly higher TH17 and TH22 (IL17A,
IL19, and S100A12 in lesional and IL-22 in nonlesional skin; P < .05) and lower
TH1/interferon (CXCL9, CXCL10, MX1, and IFNG in nonlesional skin; P < .05) gene
induction typified AD skin in Asian patients. CONCLUSION: The Asian AD phenotype
presents (even in the presence of increased IgE levels) a blended phenotype
between that of EA patients with AD and those with psoriasis, including increased
hyperplasia, parakeratosis, higher TH17 activation, and a strong TH2 component.
The relative pathogenic contributions of the TH17 and TH2 axes in creating the
Asian AD phenotype need to be tested in future clinical trials with appropriate
targeted therapeutics.
PMID- 26428955
TI - Analysis of cross-reactivity among radiocontrast media in 97 hypersensitivity
reactions.
PMID- 26428956
TI - Sparse deconvolution of higher order tensor for fiber orientation distribution
estimation.
AB - PURPOSE: Higher order tensor (HOT) imaging approaches based on the spherical
deconvolution framework have attracted much interest for their effectiveness in
estimating fiber orientation distribution (FOD). However, sparse regularization
techniques are still needed to obtain stable FOD in solving the deconvolution
problem, particularly in very high orders. Our goal is to adequately characterize
the actual sparsity lying in the FOD domain to develop accurate estimation
approach for fiber orientation in HOT framework. MATERIALS AND METHODS: We
propose a sparse HOT regularization model by enforcing the sparse constraint
directly on the representation of FOD instead of imposing it on coefficients of
basis function. Then, we incorporate both the stabilizing effect of the l2
penalty and the sparsity encouraging effect of the l1 penalty in the sparse model
to adequately characterize the actual sparsity lying in the FOD domain.
Furthermore, a weighted regularization scheme is developed to iteratively solve
the deconvolution problem. The deconvolution technique is compared against
existing methods using l2 or l1 regularizer and tested on synthetic data and real
human brain. RESULTS: Experiments were conducted on synthetic data and real human
brain data. The synthetic experimental results indicate that crossing fibers are
more easily detected and the angular resolution limit is improved by our method
by approximately 20 degrees -30 degrees compared to existing HOT method. The
detection accuracy is considerably improved compared with that of spherical
deconvolution approaches using the l2 regularizer and the reweighted l1 scheme.
CONCLUSIONS: Results of testing the deconvolution technique demonstrate that it
allows HOTs to obtain increasingly clean and sharp FOD, which in turn
significantly increases the angular resolution of current HOT methods. With
sparsity on FOD domain, this method efficiently improves the ability of HOT in
resolving crossing fibers.
PMID- 26428957
TI - Bioavailable vitamin D levels are reduced and correlate with bone mineral density
and markers of mineral metabolism in adults with nephrotic syndrome.
AB - AIM: Blood levels of 25-hydroxyvitamin D [25(OH) D] are reduced in patients with
nephrotic syndrome (NS). The lowering is thought to be due to urinary loss of
vitamin D binding protein (DBP). A link between vitamin D deficiency and bone
disease or markers of mineral metabolism has not yet been shown in NS. We
hypothesized that alterations in bioavailable vitamin D levels might be linked to
these abnormalities in NS. METHODS: We measured circulating levels of 25(OH)D,
1,25-dihydroxyvitamin D [1,25(OH)2 D], DBP, serum albumin and intact parathyroid
hormone (iPTH) in 106 adults with sporadic idiopathic NS and 40 healthy controls.
Bioavailable vitamin D was calculated from previously validated formulae. Bone
mineral density (BMD) was measured at left hip (neck of femur) by DEXA. RESULTS:
Compared to healthy controls, total and bioavailable 25(OH)D levels were
significantly reduced in patients with NS as compared to healthy controls. Among
the nephrotic patients, BMD was positively correlated with bioavailable 25(OH)D
(r = 0.358; P = 0.0002) but not with total 25(OH)D (r = 0.174; P = 0.079). Total
1,25(OH)2 D and bioavailable 1,25(OH)2 D did not correlate with BMD (r = 0.131; P
= 0.206 and r = 0.107, P = 0.295). Bioavailable 25(OH)D levels showed a strong
inverse correlation with iPTH on univariate (r = -0.457; P < 0.0001) and
multivariate (beta=-0.453, P < 0.0001) analyses. CONCLUSIONS: We conclude that
bioavailable 25(OH)D is a better measure of vitamin D status with respect of BMD
and mineral metabolism in patients of nephrotic syndrome.
PMID- 26428959
TI - Risk factors for meticillin-resistant Staphylococcus aureus colonization in
dialysis patients: a meta-analysis.
AB - BACKGROUND: Patients on dialysis are particularly vulnerable to meticillin
resistant Staphylococcus aureus (MRSA) infections and MRSA colonization is
associated with increased risk for severe infections in this population. AIM:
Determination of risk factors for MRSA colonization among dialysis patients.
METHODS: This is a systematic review and meta-analysis of studies reporting risk
factors of MRSA colonization. We performed a PubMed and EMBASE literature search
to identify all studies on risk factors for MRSA colonization among patients
undergoing dialysis treatment. Previous hospitalization, type of dialysis access,
comorbid conditions, dialysis vintage, gender, length of time on dialysis, and
previous antibiotic use were extracted and assessed for possible association with
MRSA colonization in this population. FINDINGS: Ten out of 8252 articles,
presenting data on 2364 dialysis patients, were included. We found that
hospitalization within the previous 12 months [odds ratio (OR): 1.93; 95%
confidence interval (CI): 1.04-3.58] and the use of temporary dialysis access
(relative risk: 1.66; 95% CI: 1.06-2.60) were associated with a significantly
higher risk of MRSA colonization. MRSA carriage was associated with lower serum
albumin levels compared to non-carriage (OR: 0.8; 95% CI: 0.68-0.95) and was
higher among patients with chronic lung disease (OR: 2.16; 95% CI: 1.04-4.51).
There were no data on patients undergoing peritoneal dialysis. CONCLUSION: Active
surveillance approaches, including potential decolonization strategies, are
suggested to focus on these subgroups of haemodialysis patients with
hospitalization within the previous year, temporary dialysis access, lower serum
albumin levels, and chronic lung disease comorbidity.
PMID- 26428958
TI - Primary and Secondary HIV Prevention Among Persons with Severe Mental Illness:
Recent Findings.
AB - Persons with severe mental illness (SMI) have been disproportionately affected by
the HIV epidemic, with higher rates of HIV prevalence and morbidity than the
general population. Recent research has advanced our understanding of the complex
factors that influence primary and secondary HIV prevention for those with SMI.
Sex risk in this population is associated with socioeconomic factors (e.g., low
income, history of verbal violence) and other health risk behaviors (e.g.,
substance use, no prior HIV testing). Several interventions are effective at
reducing risk behavior, and reviews highlight the need for more well-controlled
studies that assess long-term outcomes. Recent research has elucidated barriers
that interfere with HIV treatment for SMI populations, including individual
(e.g., apathy, substance use), social (e.g., stigma), and system factors (e.g.,
transportation, clinic wait times). Interventions that coordinate HIV care for
individuals with SMI show promise as cost-effective methods for improving
medication adherence and quality of life.
PMID- 26428960
TI - Written versus verbal information for patients' education on healthcare
associated infections: a cross-sectional study.
AB - In 2008, Piedmont region, Italy, recommended delivering written information on
healthcare-associated infection (HCAI) to every patient admitted to hospitals. We
interviewed 363 patients admitted to five hospitals to evaluate whether patients
who received written information were more informed about HCAI than the other
patients. We found no statistically significant difference between the two
groups. We did observe that knowledge of HCAI was significantly lower among women
and significantly higher among patients with higher education and those admitted
to a surgical ward.
PMID- 26428961
TI - Ebola: Lessons learned.
PMID- 26428962
TI - Nososcomial transmission of viral haemorrhagic fever in South Africa.
AB - Recent events in West Africa have highlighted the potential for the viral
haemorrhagic fevers (VHFs) to cause considerable mortality and morbidity among
heathcare workers. However, this is not a new threat as, although the risk is
currently increased, it has always been present. In South Africa (SA) the only
endemic haemorrhagic fever is Crimean-Congo haemorrhagic fever, transmitted by
the Hyalomma tick, which is ubiquitous in cattle farming areas. Johannesburg, the
commercial and transport hub of SA, is unusual in that all cases of VHF seen
there are imported, either from rural areas in SA or from countries to the north.
Johannesburg functions as the gateway to and from the rest of Africa, and as a
destination for more affluent residents of neighbouring countries seeking medical
attention. Numerous outbreaks of nosocomial infection have occurred in SA, and
these are described in the form of brief case reports.
PMID- 26428963
TI - Subacute sclerosing panencephalitis in South African children following the
measles outbreak between 2009 and 2011.
AB - Between 2009 and 2011, there was an outbreak of measles throughout South Africa
(SA). The largest age category infected was children<5 years of age. In 2014,
four patients, with a median age of 4 years and 5 months (range 4 years 3 months
4.5 years), three males and one female, presented with subacute sclerosing
panencephalitis (SSPE). All were infected with measles during the period of the
2009-2011 outbreak in early infancy, at a time when their immune systems were
immature and before they were vaccinated against the measles virus. One patient
was immunocompromised, with vertically acquired HIV infection. All the children
presented with cognitive and behavioural decline, abnormal movements and
medically intractable myoclonic and atonic seizures. Outcome was poor in all and
no reversibility was evident with standard therapeutic interventions. Optimal
seizure control with carbamazepine is reported in patients with SSPE. Three of
our patients who received carbamazepine experienced improved seizure control, but
their neuroregression continued. Since submission of this case series, patient 1
(see Table 1) has died, and a further child has presented with the same clinical
phenotype as described. On the basis of this clustering of patients in the
Western Cape Province, SA, it is important to screen children admitted with acute
cognitive decline and intractable seizures for SSPE, especially those who were
infants during the measles outbreak.
PMID- 26428964
TI - A human perspective on body donation: A case study from a psychosocial
perspective.
AB - Using a case study of how a son consented to his mother becoming a body donor,
the factors that may have contributed to that decision are outlined. Social and
psychological considerations about body donation in general are presented. These
are followed by suggestions for organisational improvements for healthcare
facilities and medical schools, including ease of access to accurate information
for both medical professionals and members of the public. Finally, it is
recommended that medical school staff dealing with potential donors and their
families should be trained to communicate empathically and with compassion.
PMID- 26428965
TI - Endoscopic lung volume reduction in severe emphysema.
AB - Therapeutic options in severe emphysema are limited. Endoscopic lung volume
reduction (ELVR) refers to bronchoscopically inducing volume loss to improve
pulmonary mechanics and compliance, thereby reducing the work of breathing.
Globally, this technique is increasingly used as treatment for advanced emphysema
with the aim of obtaining similar functional advantages to surgical lung volume
reduction, while reducing risks and costs. There is a growing body of evidence
that certain well-defined subgroups of patients with advanced emphysema benefit
from ELVR, provided that a systematic approach is followed and selection criteria
are met. In addition to endobronchial valves, ELVR using endobronchial coils is
now available in South Africa. The high cost of these interventions underscores
the need for careful patient selection to best identify those likely to benefit
from such procedures.
PMID- 26428966
TI - Implementation of electronic scripts in South Africa.
AB - The legal framework in South Africa (SA) provides for strict requirements
regarding prescriptions. However, pharmacists are still confronted daily with
illegible handwritten scripts, increasing the risk of medication errors. E
prescribing is being implemented in SA to overcome these disadvantages. The
general regulations made in terms of the Medicines and Related Substances Act as
well as the Electronic Communications and Transactions Act must be read
conjointly for the purposes of understanding the legal framework of electronic
prescriptions in SA.
PMID- 26428967
TI - Recommendations for the use of bronchial thermoplasty in the management of severe
asthma.
AB - There are approximately 3 million asthma suffers in South Africa, and the
national death rate is ranked as one of the highest in the world. Approximately
5% have severe asthma (uncontrolled despite being adherent on maximal and
optimised therapy). Such uncontrolled asthma is associated with high healthcare
expenditure and may require treatment with anti-IgE and/or systemic
corticosteroids, in addition to inhaler therapy and oral agents. These treatments
may be costly, and those such as oral corticosteroids may have potential serious
adverse events. There is therefore a need for more effective, affordable and safe
therapies for asthma. A new modality of treatment, bronchial thermoplasty (BT),
has recently been developed and approved for the treatment of severe asthma. BT
involves delivering radio frequency-generated thermal energy to the airways, with
the goal of reducing airway-specific smooth-muscle mass. Several clinical studies
have confirmed that BT is effective and safe, that it improves control and
quality of life in patients whose asthma remains severe despite optimal medical
therapy, and that the beneficial effects are sustained for at least 5 years. We
provide recommendations for the management of severe asthma, with an emphasis on
the role of BT, and endorse the use of BT in patients with severe persistent
asthma who remain uncontrolled despite optimal medical therapy as outlined in
steps 4 and 5 of the British Thoracic Society (BTS)/Scottish Intercollegiate
Guidelines Network (SIGN), UK National Institute of Clinical Excellence (NICE)
and Global Initiative for Asthma (GINA) guidelines. We outline the context in
which BT should be used, how it works and associated potential adverse events and
contraindications, and also review unanswered questions and controversies.
PMID- 26428968
TI - Recommendations for the anticoagulation of pregnant patients with mechanical
heart valves.
AB - BACKGROUND: The management of pregnant patients with mechanical heart valves
remains challenging because there are no large randomised studies to provide
guidelines for effective anticoagulant therapy. Both vitamin K antagonists and
heparins may be associated with maternal and foetal adverse events. METHOD: The
Southern African Society of Thrombosis and Haemostasis reviewed available
literature and comprehensive evidence-based guidelines for the anticoagulation of
pregnant patients with mechanical heart valves. A draft document was produced and
revised by consensus agreement. The guidelines were adjudicated by independent
international experts to avoid local bias. RESULTS AND CONCLUSION: We present
concise, practical guidelines for the clinical management of pregnant patients
with mechanical heart valves. Recommendations reflect current best practice which
will hopefully lead to improved anticoagulation practice in this select group of
high risk patients.
PMID- 26428969
TI - National Health Insurance in South Africa: Relevance of a national priority
setting agency.
PMID- 26428970
TI - Reforming South Africa's procedures for granting patents to improve medicine
access.
PMID- 26428971
TI - South African Guidelines Excellence (SAGE): Clinical practice guidelines--quality
and credibility.
PMID- 26428972
TI - Gender and sexual diversity--changing paradigms in an ever-changing world.
PMID- 26428973
TI - Viral haemorrhagic fevers in South Africa.
AB - Viral haemorrhagic fevers (VHFs) include a diverse array of diseases caused by a
broad range of viruses transmitted from various animal hosts and originating from
almost all the continents in the world. These are potentially fatal and highly
transmissible diseases without specific treatments or prophylactic vaccines. As
has been demonstrated during the Ebola virus disease outbreak in West Africa, the
consequences of VHFs are not limited to specific countries - they may become
epidemic, and may have considerable economic impact and disrupt local public
health and social service structures. Intensive public health intervention is
necessary to contain these diseases. Here we provide a concise overview of the
VHFs that are of current public health importance to South Africa.
PMID- 26428974
TI - Antimicrobial resistance of bacteria isolated from patients with bloodstream
infections at a tertiary care hospital in the Democratic Republic of the Congo.
AB - BACKGROUND: Bloodstream infection (BSI) is a life-threatening condition that
requires rapid antimicrobial treatment. METHODS: We determined the prevalence of
bacterial isolates associated with BSI at Bukavu General Hospital (BGH), South
Kivu Province, Democratic Republic of the Congo, and their patterns of
susceptibility to antimicrobial drugs, from February 2013 to January 2014.
RESULTS: We cultured 112 clinically relevant isolates from 320 blood cultures. Of
these isolates, 104 (92.9%) were Gram-negative bacteria (GNB), with 103 bacilli
(92.0%) and one coccus (0.9%). Among GNB, Escherichia coli (51.9%), Klebsiella
spp. (20.2%), Enterobacter spp. (6.7%), Shigella spp. (5.8%) and Salmonella spp.
(4.8%) were the most frequent agents causing BSIs. Other GNB isolates included
Proteus spp., Citrobacter spp. and Pseudomonas aeruginosa (both 2.9%), and
Acinetobacter spp. and Neisseria spp. (both 0.9%). High rates of resistance to co
trimoxazole (100%), erythromycin (100%) and ampicillin (66.7-100%) and moderate
to high resistance to ciprofloxacin, ceftazidime, ceftriaxone, cefuroxime and
cefepime were observed among GNB. Furthermore, there were high rates of multidrug
resistance and of extended-spectrum beta-lactamase (ESBL) production phenotype
among Enterobacteriaceae. Gram-positive bacteria included three Staphylococcus
aureus isolates (2.7%), four oxacillin-resistant coagulase-negative staphylococci
(CoNS) isolates (3.6%) and one Streptococcus pneumoniae (0.9%). No oxacillin
resistant S. aureus was isolated. Among clinically relevant staphylococci,
susceptibility to co-trimoxazole and ampicillin was low (0-25%). In addition, 58
contaminant CoNS were isolated from blood cultures, and the calculated ratio of
contaminants to pathogens in blood cultures was 1:2. CONCLUSIONS: Multidrug
resistant and ESBL-producing GNB are the leading cause of BSI at BGH.
PMID- 26428975
TI - The role of point-of-care blood testing for ketones in the diagnosis of diabetic
ketoacidosis.
AB - BACKGROUND: Urine dipstick testing for ketones is widely used when diabetic
ketoacidosis (DKA) is suspected in patients with hyperglycaemia. If urinary
ketones are positive, patients are referred for further management--often
inappropriately, as the test is a poor surrogate for plasma ketones. Plasma beta
hydroxybutyrate (beta-OHB) levels>3 mmol/L are diagnostic of DKA, while levels<1
mmol/L are insignificant. OBJECTIVES: To evaluate a hand-held electrochemical
(point-of-care testing; POCT) ketone monitor and compare it with the gold
standard manual enzymatic method (MEM) for detection of plasma ketones. METHODS:
In a prospective and comparative study, we evaluated the measurement of beta-OHB
by means of POCT and the MEM in 61 consecutive samples from patients with
suspected DKA at Tygerberg and Karl Bremer hospitals, Cape Town, South Africa.
Capillary (for POCT) and plasma samples (for the MEM) were obtained
simultaneously and compared for accuracy. Precision was assessed with control
samples. RESULTS: The POCT method was precise (coefficient of variation <4.5%),
and there was a good correlation between the two methods (r=0.95). Regression
analysis showed a proportional bias, with POCT reading higher than the MEM.
However, when assessed at the relevant medical decision limits (beta-OHB>3 mmol/L
and <1 mmol/L), the total allowable error (bias+imprecision) was not exceeded.
Patients will therefore still be classified correctly. The POCT method had a
sensitivity of 100% and specificity of 89% for DKA (beta-OHB>3 mmol/L), while at
levels<1 mmol/L sensitivity was 100% and specificity 87.5%. CONCLUSION: The POCT
device provides an accurate and precise result and can be used as an alternative
to the MEM in the diagnosis of DKA.
PMID- 26428976
TI - Reproductive knowledge and use of contraception among women with diabetes.
AB - BACKGROUND: Poorly controlled diabetes is associated with poor maternal and fetal
outcomes, yet many women become pregnant before establishing control. Reducing
unintended pregnancies is a vital step towards improving perinatal and maternal
morbidity and mortality. OBJECTIVES: To assess the reproductive knowledge and use
of contraception in women of reproductive age attending diabetes outpatient
clinics. METHODS: A prospective descriptive study was conducted of women known to
have diabetes, aged 18 - 45 years, attending the diabetic clinics at Groote
Schuur Hospital or the local community health centres in Cape Town, South Africa.
A questionnaire consisting of social, demographic and family details as well as
contraceptive use and knowledge was administered. RESULTS: Some common themes
emerged, namely that 44.2% of the women with previous pregnancies had had
unintended pregnancies, and that this was more common among single (58.8%) and
younger women. Women with type 1 diabetes had better knowledge than those with
type 2 diabetes of how pregnancy affects diabetes, but better knowledge did not
translate to better contraception use. Despite the fact that 102 participants
(88.7%) attended diabetes clinics two or more times a year, knowledge of
pregnancy- and reproductive health-related complications was limited, and only 30
participants (26.1%) had received advice on contraception at these clinics.
CONCLUSION: Knowledge about the impact of diabetes on pregnancy and that of
pregnancy on diabetes was suboptimal. We recommend that reproductive health
services be included at the routine diabetes clinic visit.
PMID- 26428977
TI - Time to implement 9-month infant HIV testing in South Africa.
AB - BACKGROUND: South Africa (SA) is likely to meet the National Strategic Plan
target of <2% mother-to-child HIV transmission at 6 weeks of age in 2015.
Children infected with HIV after 6 weeks often remain undiagnosed because of poor
implementation of post-weaning and final outcome 18-month HIV testing. The World
Health Organization recommends a screening HIV rapid test (HRT) in HIV-exposed
infants at the 9-month immunisation visit to exclude postnatal infection, with a
confirmatory HIV polymerase chain reaction (PCR) test if the HRT is positive.
OBJECTIVE: To evaluate the impact of substituting this recommendation for the
post-weaning HIV testing recommended by SA guidelines. METHODS: Rates of
seroreversion and probability of infection at 9 months of age were applied to a
theoretical population of 100 HIV-exposed infants, uninfected at birth and
breastfed for 1 year with antiretroviral prophylaxis. Nine scenarios were
developed and the number of HIV PCRs saved compared with current guidelines was
calculated. RESULTS: Nine-month testing using the HRT reduced the number of
follow-up PCR tests done in all scenarios by >50%, with differences ranging from
51% to 59% and 81% to 89% for low and high seroreversion rates, respectively.
CONCLUSIONS: Nine-month testing using HRT would increase identification and early
treatment of HIV-infected infants, improve monitoring of postnatal transmission
rates, and reduce the number of HIV PCR tests done with resultant cost saving.
Training of healthcare workers implementing HRT would be required. Ongoing
efforts to improve implementation and monitoring of testing at 9 and 18 months
will be essential.
PMID- 26428978
TI - Pharmacological treatment of painful HIV-associated sensory neuropathy.
AB - BACKGROUND: HIV-associated sensory neuropathy (HIV-SN) is a common and frequently
painful complication of HIV infection and its treatment. However, few data exist
describing the frequency, type and dosage of pain medications patients are
receiving in the clinic setting to manage the painful symptoms of HIV-SN.
OBJECTIVE: To report on analgesic prescription for painful HIV-SN and factors
influencing that prescription in adults on combination antiretroviral therapy.
METHODS: Using validated case ascertainment criteria to identify patients with
painful HIV-SN, we recruited 130 HIV-positive patients with painful HIV-SN at
Chris Hani Baragwanath Hospital, Johannesburg, South Africa. Demographic and
clinical data (including current analgesic use) were collected on direct
questioning of the patients and review of the medical files. RESULTS: We found
significant associations, of moderate effect size, between higher pain intensity
and lower CD4 T-cell counts with prescription of analgesic therapy. Factors
previously identified as predicting analgesic treatment in HIV-positive
individuals (age, gender, level of education) were not associated with analgesic
use here. Consistent with national guidelines, amitriptyline was the most
commonly used agent, either alone or in combination therapy. Importantly, we also
found that despite the relatively high analgesic treatment rate in this setting,
the majority of patients described their current level of HIV-SN pain as moderate
or severe. CONCLUSION: Our findings highlight the urgent need for both better
analgesic options for HIV-SN pain treatment and ongoing training and support of
clinicians managing this common and debilitating condition.
PMID- 26428979
TI - Bone marrow aspirate microscopy v. bone marrow trephine biopsy microscopy for
detection of Mycobacterium tuberculosis infection.
AB - BACKGROUND: Tuberculosis (TB) remains a global health problem. According to the
2013 Global Report on Tuberculosis, 8.6 million people developed TB in 2012 and
1.3 million died from the disease. An estimated 13% of people who developed TB in
2012 were HIV-positive, and 75% of these lived in Africa. While pulmonary TB is
the commonest form of Mycobacterium tuberculosis infection, extrapulmonary TB is
increasingly being detected in HIV-positive patients. Definitive diagnosis of
disseminated TB is a challenge owing to atypical presentations and diagnostic
difficulties (negative chest radiograph and sputum microscopy and culture). A
rapid diagnosis of disseminated TB is desirable, as early initiation of treatment
can reduce mortality. Although TB culture is the gold standard for diagnosis of
TB, it has a long turnaround time (up to 6 weeks). OBJECTIVES: To identify a
potentially faster and more effective diagnostic strategy for disseminated TB.
METHODS: A retrospective 18-month review, conducted at a tertiary hospital,
comparing histological findings of an auramine O-stained bone marrow aspiration
(BMA) smear and a bone marrow trephine (BMT) biopsy specimen with the gold
standard of TB culture. RESULTS: Microscopic examination of BMA smears and BMT
biopsy specimens offers a rapid diagnostic strategy, with results available on
the same day for the former and within 4 days for the latter. BMT histological
examination had a significantly higher detection rate than BMA auramine O
staining compared with TB culture. CONCLUSION: We recommend that BMT biopsies
remain an essential part of the diagnostic work-up for disseminated TB.
PMID- 26428980
TI - Codeine misuse and dependence in South Africa--learning from substance abuse
treatment admissions.
AB - BACKGROUND: Misuse of prescription and over-the-counter codeine-containing
products is a global public health issue. OBJECTIVES: To investigate the extent
of treatment demand related to the misuse of codeine or codeine dependence in
South Africa (SA) and the profile of patients seeking treatment, so as to
understand the nature and extent of the problem. METHOD: Data were collected from
centres participating in the South African Community Epidemiology Network on Drug
Use in 2014. A total of 17 260 admissions were recorded. RESULTS: There were 435
recorded treatment admissions for codeine misuse or dependence as a primary or
secondary substance of abuse (2.5% of all admissions). Of treatment admissions,
137 (0.8%) involved codeine as the primary substance of abuse; 74.9% of patients
were males, with an even spread across population groups. Ages ranged from 11 to
70 years, with the highest proportion aged 20 - 29 years; >40% were referred by
self, family and/or friends, and 26.7% by health professionals; and 36.8% had
received treatment previously. The majority reported misuse of tablets/capsules,
with 17.6% reporting misuse of syrups. Oral use comprised 96.6% and daily use
63.1%. CONCLUSIONS: Data from treatment admissions related to codeine misuse and
dependence are informative, but provide an incomplete picture of the nature and
extent of codeine-related problems in SA. Other data sources must be considered
before further regulatory/policy changes regarding codeine are implemented.
PMID- 26428981
TI - Affordable moisturisers are effective in atopic eczema: A randomised controlled
trial.
AB - BACKGROUND: Many patients depend on moisturisers issued by public health services
in the management of atopic dermatitis (AD). METHODS: In a randomised controlled
trial of patients with mild to moderate AD, aged 1-12 years, study 1 compared
aqueous cream v. liquid paraffin (fragrance-free baby oil) as a soap substitute,
all patients using emulsifying ointment as moisturiser, and study 2 compared four
moisturisers, emulsifying ointment, cetomacrogol, white petroleum jelly and
glycerine/petroleum (proportion 1:2; 'the 1:2 moisturiser'), all using fragrance
free baby oil as soap substitute. Assessments were one quality of life and three
AD severity scores, at baseline and weeks 4, 8 and 12. Differences were compared
using repeated measures of analysis of variance. RESULTS: In both studies (120
children randomised, 20 in each group of the two trials) disease severity scores
declined with time. The only significant difference was in one AD severity score
(SCORing Atopic Dermatitis) in study 1, both at baseline and over time (p=0.042
and p=0.022). The groups did not differ with regard to topical steroid use or
side-effects. Itching from baby oil applied as soap was reported by four patients
in the two studies, the petroleum jelly group had more dropouts than the 1:2
moisturiser group, although this was not statistically significant, and 110
patients (91.7%) completed the trial. CONCLUSIONS: The small sample limits
generalisability, but the duration was longer than in most AD moisturiser
studies. Fragrance-free baby oil is an effective soap substitute that may be
better tolerated (if irritation occurs) as a bath additive. The home-made 1:2
moisturiser may be preferable to white petroleum jelly, but both are equivalent
to cetomacrogol and emulsifying ointment. Use of accessible moisturisers could
reduce the cost of managing mild to moderate AD.
PMID- 26428988
TI - Communication: Spectroscopic observation of the O-bonded T-shaped isomer of the
CO-CO2 dimer and two of its intermolecular frequencies.
AB - Infrared spectra in the carbon monoxide CO stretch region (~2150 cm(-1)) are
assigned to the previously unobserved O-bonded form of the CO2-CO dimer ("isomer
2"), which has a planar T-shaped structure like that of the previously observed C
bonded form ("isomer 1"), but with the CO rotated by 180 degrees . The effective
center of mass intermolecular distances are 3.58 A for isomer 2 as compared to
3.91 A for isomer 1. In addition to the fundamental band, two combination bands
are observed for isomer 2, yielding values for two intermolecular vibrational
modes: 14.19 cm(-1) for the in-plane CO bend and 22.68 cm(-1) for the out-of
plane bend.
PMID- 26428987
TI - Core diameter of bone marrow aspiration devices influences cell density of bone
marrow aspirate in patients with severe peripheral artery disease.
AB - BACKGROUND AIMS: Bone marrow (BM) transplantations are an accepted therapeutic
strategy for hematologic conditions. In the past decades, interest for BM-derived
cell therapy has extended toward the field of regenerative medicine. Irrespective
of the treatment strategy, its success depends on the amount of cells available
for transplantation. Both patient and procedural factors have been shown to
influence the cell density of the BM aspirate. In the present study, the
influence of core diameter of the BM aspiration device on cell density of the BM
aspirate is studied. METHODS: BM harvesting procedures performed in a clinical
trial investigating the effect of BM cell therapy in patients with severe
peripheral artery disease were retrospectively studied (clinicaltrials.gov
NCT00371371). Patients underwent BM harvesting through the use of either a 15
gauge (n = 85) or an 8-gauge (n = 75) needle. The numbers of harvested white
blood cells (WBC) and CD34(+) hematopoietic cells (HPC) were quantified. RESULTS:
The amount of WBC per milliliter of BM aspirate was significantly higher when the
8-gauge needle (27.8 * 10(6) WBC/mL [95%CI 25.4-30.5 * 10(6)]) was used compared
with the smaller 15-gauge core needle (20.1 * 10(6) WBC/mL [95% confidence
interval (CI), 18.7-21.7 * 10(6)], P < 0.001). For the amount of CD34(+) HPC, a
similar pattern was observed (185 * 10(3) HPC/mL [95% CI, 161-213 * 10(3)]; 114 *
10(3) HPC/mL [95% CI, 96-134 * 10(3)]; P < 0.001). CONCLUSIONS: The application
of a BM aspiration device with a larger core diameter is associated with an
increased cell density of the BM aspiration product in patients with severe
peripheral artery disease.
PMID- 26428989
TI - Communication: Broadband and ultrasensitive femtosecond time-resolved circular
dichroism spectroscopy.
AB - We report the development of broadband and sensitive time-resolved circular
dichroism (TRCD) spectroscopy by exploiting optical heterodyne detection. Using
this method, transient CD signals of submillidegree level can be detected over
the spectral range of 415-730 nm. We also demonstrate that the broadband
measurement with the aid of singular value decomposition enables the
discrimination of genuine TRCD signals from artificial optical-anisotropy, such
as linear birefringence and linear dichroism, induced by photoexcitation.
PMID- 26428991
TI - Directed HK propagator.
AB - We offer a more formal justification for the successes of our recently
communicated "directed Heller-Herman-Kluk-Kay" (DHK) time propagator by examining
its performance in one-dimensional bound systems which exhibit at least quasi
periodic motion. DHK is distinguished by its single one-dimensional integral--a
vast simplification over the usual 2N-dimensional integral in full Heller-Herman
Kluk-Kay (for an N-dimensional system). We find that DHK accurately captures
particular coherent state autocorrelations when its single integral is chosen to
lie along these states' fastest growing manifold, as long as it is not
perpendicular to their action gradient. Moreover, the larger the action gradient,
the better DHK will perform. We numerically examine DHK's accuracy in a one
dimensional quartic oscillator and illustrate that these conditions are
frequently satisfied such that the method performs well. This lends some
explanation for why DHK frequently seems to work so well and suggests that it may
be applicable to systems exhibiting quite strong anharmonicity.
PMID- 26428990
TI - Memetic algorithms for ligand expulsion from protein cavities.
AB - Ligand diffusion through a protein interior is a fundamental process governing
biological signaling and enzymatic catalysis. A complex topology of channels in
proteins leads often to difficulties in modeling ligand escape pathways by
classical molecular dynamics simulations. In this paper, two novel memetic
methods for searching the exit paths and cavity space exploration are proposed:
Memory Enhanced Random Acceleration (MERA) Molecular Dynamics (MD) and Immune
Algorithm (IA). In MERA, a pheromone concept is introduced to optimize an
expulsion force. In IA, hybrid learning protocols are exploited to predict ligand
exit paths. They are tested on three protein channels with increasing complexity:
M2 muscarinic G-protein-coupled receptor, enzyme nitrile hydratase, and heme
protein cytochrome P450cam. In these cases, the memetic methods outperform
simulated annealing and random acceleration molecular dynamics. The proposed
algorithms are general and appropriate in all problems where an accelerated
transport of an object through a network of channels is studied.
PMID- 26428992
TI - Construction of exchange-correlation functionals through interpolation between
the non-interacting and the strong-correlation limit.
AB - Drawing on the adiabatic connection of density functional theory, exchange
correlation functionals of Kohn-Sham density functional theory are constructed
which interpolate between the extreme limits of the electron-electron interaction
strength. The first limit is the non-interacting one, where there is only
exchange. The second limit is the strong correlated one, characterized as the
minimum of the electron-electron repulsion energy. The exchange-correlation
energy in the strong-correlation limit is approximated through a model for the
exchange-correlation hole that is referred to as nonlocal-radius model [L. O.
Wagner and P. Gori-Giorgi, Phys. Rev. A 90, 052512 (2014)]. Using the non
interacting and strong-correlated extremes, various interpolation schemes are
presented that yield new approximations to the adiabatic connection and thus to
the exchange-correlation energy. Some of them rely on empiricism while others do
not. Several of the proposed approximations yield the exact exchange-correlation
energy for one-electron systems where local and semi-local approximations often
fail badly. Other proposed approximations generalize existing global hybrids by
using a fraction of the exchange-correlation energy in the strong-correlation
limit to replace an equal fraction of the semi-local approximation to the
exchange-correlation energy in the strong-correlation limit. The performance of
the proposed approximations is evaluated for molecular atomization energies,
total atomic energies, and ionization potentials.
PMID- 26428993
TI - An enhanced version of the heat exchange algorithm with excellent energy
conservation properties.
AB - We propose a new algorithm for non-equilibrium molecular dynamics simulations of
thermal gradients. The algorithm is an extension of the heat exchange algorithm
developed by Hafskjold et al. [Mol. Phys. 80, 1389 (1993); 81, 251 (1994)], in
which a certain amount of heat is added to one region and removed from another by
rescaling velocities appropriately. Since the amount of added and removed heat is
the same and the dynamics between velocity rescaling steps is Hamiltonian, the
heat exchange algorithm is expected to conserve the energy. However, it has been
reported previously that the original version of the heat exchange algorithm
exhibits a pronounced drift in the total energy, the exact cause of which
remained hitherto unclear. Here, we show that the energy drift is due to the
truncation error arising from the operator splitting and suggest an additional
coordinate integration step as a remedy. The new algorithm retains all the
advantages of the original one whilst exhibiting excellent energy conservation as
illustrated for a Lennard-Jones liquid and SPC/E water.
PMID- 26428994
TI - Conformational sampling enhancement of replica exchange molecular dynamics
simulations using swarm particle intelligence.
AB - In this paper, we present a new method based on swarm particle social
intelligence for use in replica exchange molecular dynamics simulations. In this
method, the replicas (representing the different system configurations) are
allowed communicating with each other through the individual and social
knowledge, in additional to considering them as a collection of real particles
interacting through the Newtonian forces. The new method is based on the
modification of the equations of motion in such way that the replicas are driven
towards the global energy minimum. The method was tested for the Lennard-Jones
clusters of N = 4, 5, and 6 atoms. Our results showed that the new method is more
efficient than the conventional replica exchange method under the same practical
conditions. In particular, the new method performed better on optimizing the
distribution of the replicas among the thermostats with time and, in addition,
ergodic convergence is observed to be faster. We also introduce a weighted
histogram analysis method allowing analyzing the data from simulations by
combining data from all of the replicas and rigorously removing the inserted
bias.
PMID- 26428995
TI - An EQT-based cDFT approach for a confined Lennard-Jones fluid mixture.
AB - Empirical potential-based quasi-continuum theory (EQT) provides a route to
incorporate atomistic detail into continuum framework such as the Nernst-Planck
equation. EQT can also be used to construct a grand potential functional for
classical density functional theory (cDFT). The combination of EQT and cDFT
provides a simple and fast approach to predict the inhomogeneous density,
potential profiles, and thermodynamic properties of confined fluids. We extend
the EQT-cDFT approach to confined fluid mixtures and demonstrate it by simulating
a mixture of methane and hydrogen inside slit-like channels of graphene. We show
that the EQT-cDFT predictions for the structure of the confined fluid mixture
compare well with the molecular dynamics simulation results. In addition, our
results show that graphene slit nanopores exhibit a selective adsorption of
methane over hydrogen.
PMID- 26428996
TI - Adapting algebraic diagrammatic construction schemes for the polarization
propagator to problems with multi-reference electronic ground states exploiting
the spin-flip ansatz.
AB - For the investigation of molecular systems with electronic ground states
exhibiting multi-reference character, a spin-flip (SF) version of the algebraic
diagrammatic construction (ADC) scheme for the polarization propagator up to
third order perturbation theory (SF-ADC(3)) is derived via the intermediate state
representation and implemented into our existing ADC computer program adcman. The
accuracy of these new SF-ADC(n) approaches is tested on typical situations, in
which the ground state acquires multi-reference character, like bond breaking of
H2 and HF, the torsional motion of ethylene, and the excited states of
rectangular and square-planar cyclobutadiene. Overall, the results of SF-ADC(n)
reveal an accurate description of these systems in comparison with standard multi
reference methods. Thus, the spin-flip versions of ADC are easy-to-use methods
for the calculation of "few-reference" systems, which possess a stable single
reference triplet ground state.
PMID- 26428997
TI - Analytical optimal pulse shapes obtained with the aid of genetic algorithms.
AB - We propose a methodology to design optimal pulses for achieving quantum optimal
control on molecular systems. Our approach constrains pulse shapes to linear
combinations of a fixed number of experimentally relevant pulse functions.
Quantum optimal control is obtained by maximizing a multi-target fitness function
using genetic algorithms. As a first application of the methodology, we generated
an optimal pulse that successfully maximized the yield on a selected dissociation
channel of a diatomic molecule. Our pulse is obtained as a linear combination of
linearly chirped pulse functions. Data recorded along the evolution of the
genetic algorithm contained important information regarding the interplay between
radiative and diabatic processes. We performed a principal component analysis on
these data to retrieve the most relevant processes along the optimal path. Our
proposed methodology could be useful for performing quantum optimal control on
more complex systems by employing a wider variety of pulse shape functions.
PMID- 26428998
TI - Grand canonical Monte Carlo using solvent repacking: Application to phase
behavior of hard disk mixtures.
AB - A new "solvent repacking Monte Carlo" strategy for performing grand canonical
ensemble simulations in condensed phases is introduced and applied to the study
of hard-disk systems. The strategy is based on the configuration-bias approach,
but uses an auxiliary biasing potential to improve the efficiency of packing
multiple solvent particles in the cavity formed by removing one large solute. The
method has been applied to study the coexistence of ordered and isotropic phases
in three binary mixtures of hard disks with a small mole fraction (xL < 0.02) of
the larger "solute" component. A chemical potential of 12.81 +/- 0.01 kBT was
found to correspond to the freezing transition of the pure hard disk "solvent."
Simulations permitted the study of partitioning of large disks between ordered
and isotropic phases, which showed a distinct non-monotonic dependence on size;
the isotropic phase was enriched approximately 10-fold, 20-fold, and 5-fold over
the coexisting ordered phases at diameter ratios d = 1.4, 2.5, and 3,
respectively. Mixing of large and small disks within both phases near coexistence
was strongly non-ideal in spite of the dilution. Structures of systems near
coexistence were analyzed to determine correlations between large disks'
positions within each phase, the orientational correlation length of small disks
within the fluid phases, and the nature of translational order in the ordered
phase. The analyses indicate that the ordered phase coexists with an isotropic
phase resembling a nanoemulsion of ordered domains of small disks, with large
disks enriched at the disordered domain interfaces.
PMID- 26428999
TI - DGDFT: A massively parallel method for large scale density functional theory
calculations.
AB - We describe a massively parallel implementation of the recently developed
discontinuous Galerkin density functional theory (DGDFT) method, for efficient
large-scale Kohn-Sham DFT based electronic structure calculations. The DGDFT
method uses adaptive local basis (ALB) functions generated on-the-fly during the
self-consistent field iteration to represent the solution to the Kohn-Sham
equations. The use of the ALB set provides a systematic way to improve the
accuracy of the approximation. By using the pole expansion and selected inversion
technique to compute electron density, energy, and atomic forces, we can make the
computational complexity of DGDFT scale at most quadratically with respect to the
number of electrons for both insulating and metallic systems. We show that for
the two-dimensional (2D) phosphorene systems studied here, using 37 basis
functions per atom allows us to reach an accuracy level of 1.3 * 10(-4)
Hartree/atom in terms of the error of energy and 6.2 * 10(-4) Hartree/bohr in
terms of the error of atomic force, respectively. DGDFT can achieve 80% parallel
efficiency on 128,000 high performance computing cores when it is used to study
the electronic structure of 2D phosphorene systems with 3500-14 000 atoms. This
high parallel efficiency results from a two-level parallelization scheme that we
will describe in detail.
PMID- 26429000
TI - Relaxation mode analysis and Markov state relaxation mode analysis for chignolin
in aqueous solution near a transition temperature.
AB - It is important to extract reaction coordinates or order parameters from protein
simulations in order to investigate the local minimum-energy states and the
transitions between them. The most popular method to obtain such data is
principal component analysis, which extracts modes of large conformational
fluctuations around an average structure. We recently applied relaxation mode
analysis for protein systems, which approximately estimates the slow relaxation
modes and times from a simulation and enables investigations of the dynamic
properties underlying the structural fluctuations of proteins. In this study, we
apply this relaxation mode analysis to extract reaction coordinates for a system
in which there are large conformational changes such as those commonly observed
in protein folding/unfolding. We performed a 750-ns simulation of chignolin
protein near its folding transition temperature and observed many transitions
between the most stable, misfolded, intermediate, and unfolded states. We then
applied principal component analysis and relaxation mode analysis to the system.
In the relaxation mode analysis, we could automatically extract good reaction
coordinates. The free-energy surfaces provide a clearer understanding of the
transitions not only between local minimum-energy states but also between the
folded and unfolded states, even though the simulation involved large
conformational changes. Moreover, we propose a new analysis method called Markov
state relaxation mode analysis. We applied the new method to states with slow
relaxation, which are defined by the free-energy surface obtained in the
relaxation mode analysis. Finally, the relaxation times of the states obtained
with a simple Markov state model and the proposed Markov state relaxation mode
analysis are compared and discussed.
PMID- 26429001
TI - Direct assignment of molecular vibrations via normal mode analysis of the neutron
dynamic pair distribution function technique.
AB - For over a century, vibrational spectroscopy has enhanced the study of materials.
Yet, assignment of particular molecular motions to vibrational excitations has
relied on indirect methods. Here, we demonstrate that applying group theoretical
methods to the dynamic pair distribution function analysis of neutron scattering
data provides direct access to the individual atomic displacements responsible
for these excitations. Applied to the molecule-based frustrated magnet with a
potential magnetic valence-bond state, LiZn2Mo3O8, this approach allows direct
assignment of the constrained rotational mode of Mo3O13 clusters and internal
modes of MoO6 polyhedra. We anticipate that coupling this well known data
analysis technique with dynamic pair distribution function analysis will have
broad application in connecting structural dynamics to physical properties in a
wide range of molecular and solid state systems.
PMID- 26429002
TI - Elucidation of reactive wavepackets by two-dimensional resonance Raman
spectroscopy.
AB - Traditional second-order kinetic theories fail to describe sub-picosecond
photochemical reactions when solvation and vibrational dephasing undermine the
assumption of equilibrium initial conditions. Four-wave mixing spectroscopies may
reveal insights into such non-equilibrium processes but are limited by the single
"population time" available in these types of experiments. Here, we use two
dimensional resonance Raman (2DRR) spectroscopy to expose correlations between
coherent nuclear motions of the reactant and product in the photodissociation
reaction of triiodide. It is shown that the transition of a nuclear wavepacket
from the reactant (triiodide) to product (diiodide) states gives rise to a unique
pattern of 2DRR resonances. Peaks associated with this coherent reaction
mechanism are readily assigned, because they are isolated in particular quadrants
of the 2DRR spectrum. A theoretical model in which the chemical reaction is
treated as a vibronic coherence transfer transition from triiodide to diiodide
reproduces the patterns of 2DRR resonances detected in experiments. These signal
components reveal correlation between the nonequilibrium geometry of triiodide
and the vibrational coherence frequency of diiodide. The 2DRR signatures of
coherent reaction mechanisms established in this work may generalize to studies
of ultrafast energy and charge transfer processes.
PMID- 26429003
TI - A method for the direct measurement of electronic site populations in a molecular
aggregate using two-dimensional electronic-vibrational spectroscopy.
AB - Two dimensional electronic spectroscopy has proved to be a valuable experimental
technique to reveal electronic excitation dynamics in photosynthetic pigment
protein complexes, nanoscale semiconductors, organic photovoltaic materials, and
many other types of systems. It does not, however, provide direct information
concerning the spatial structure and dynamics of excitons. 2D infrared
spectroscopy has become a widely used tool for studying structural dynamics but
is incapable of directly providing information concerning electronic excited
states. 2D electronic-vibrational (2DEV) spectroscopy provides a link between
these domains, directly connecting the electronic excitation with the vibrational
structure of the system under study. In this work, we derive response functions
for the 2DEV spectrum of a molecular dimer and propose a method by which 2DEV
spectra could be used to directly measure the electronic site populations as a
function of time following the initial electronic excitation. We present results
from the response function simulations which show that our proposed approach is
substantially valid. This method provides, to our knowledge, the first direct
experimental method for measuring the electronic excited state dynamics in the
spatial domain, on the molecular scale.
PMID- 26429004
TI - Spectral reconstruction analysis for enhancing signal-to-noise in time-resolved
spectroscopies.
AB - We demonstrate a new spectral analysis for the enhancement of the signal-to-noise
ratio (SNR) in time-resolved spectroscopies. Unlike the simple linear average
which produces a single representative spectrum with enhanced SNR, this Spectral
Reconstruction analysis (SRa) improves the SNR (by a factor of ca. 0.6?n) for all
n experimentally recorded time-resolved spectra. SRa operates by eliminating
noise in the temporal domain, thereby attenuating noise in the spectral domain,
as follows: Temporal profiles at each measured frequency are fit to a generic
mathematical function that best represents the temporal evolution; spectra at
each time are then reconstructed with data points from the fitted profiles. The
SRa method is validated with simulated control spectral data sets. Finally, we
apply SRa to two distinct experimentally measured sets of time-resolved IR
emission spectra: (1) UV photolysis of carbonyl cyanide and (2) UV photolysis of
vinyl cyanide.
PMID- 26429005
TI - Hyper-Rayleigh scattering in centrosymmetric systems.
AB - Hyper-Rayleigh scattering (HRS) is an incoherent mechanism for optical second
harmonic generation. The frequency-doubled light that emerges from this mechanism
is not emitted in a laser-like manner, in the forward direction; it is scattered
in all directions. The underlying theory for this effect involves terms that are
quadratic in the incident field and involves an even-order optical susceptibility
(for a molecule, its associated hyperpolarizability). In consequence, HRS is
often regarded as formally forbidden in centrosymmetric media. However, for the
fundamental three-photon interaction, theory based on the standard electric
dipole approximation, representable as E1(3), does not account for all
experimental observations. The relevant results emerge upon extending the theory
to include E1(2)M1 and E1(2)E2 contributions, incorporating one magnetic dipolar
or electric quadrupolar interaction, respectively, to a consistent level of
multipolar expansion. Both additional interactions require the deployment of
higher orders in the multipole expansion, with the E1(2)E2 interaction analogous
in rank and parity to a four-wave susceptibility. To elicit the correct form of
response from fluid or disordered media invites a tensor representation which
does not oversimplify the molecular components, yet which can produce results to
facilitate the interpretation of experimental observations. The detailed
derivation in this work leads to results which are summarized for the following:
perpendicular detection of polarization components both parallel and
perpendicular to the pump radiation, leading to distinct polarization ratio
results, as well as a reversal ratio for forward scattered circular
polarizations. The results provide a route to handling data with direct physical
interpretation, to enable the more sophisticated design of molecules with sought
nonlinear optical properties.
PMID- 26429006
TI - Dissociation energies of Ag-RG (RG = Ar, Kr, Xe) and AgO molecules from velocity
map imaging studies.
AB - The near ultraviolet photodissociation dynamics of silver atom-rare gas dimers
have been studied by velocity map imaging. Ag-RG (RG = Ar, Kr, Xe) species
generated by laser ablation are excited in the region of the C ((2)Sigma(+))<-X
((2)Sigma(+)) continuum leading to direct, near-threshold dissociation generating
Ag* ((2)P3/2) + RG ((1)S0) products. Images recorded at excitation wavelengths
throughout the C ((2)Sigma(+))<-X ((2)Sigma(+)) continuum, coupled with known
atomic energy levels, permit determination of the ground X ((2)Sigma(+)) state
dissociation energies of 85.9 +/- 23.4 cm(-1) (Ag-Ar), 149.3 +/- 22.4 cm(-1) (Ag
Kr), and 256.3 +/- 16.0 cm(-1) (Ag-Xe). Three additional photolysis processes,
each yielding Ag atom photoproducts, are observed in the same spectral region.
Two of these are markedly enhanced in intensity upon seeding the molecular beam
with nitrous oxide, and are assigned to photodissociation of AgO at the two
photon level. These features yield an improved ground state dissociation energy
for AgO of 15 965 +/- 81 cm(-1), which is in good agreement with high level
calculations. The third process results in Ag atom fragments whose kinetic energy
shows anomalously weak photon energy dependence and is assigned tentatively to
dissociative ionization of the silver dimer Ag2.
PMID- 26429007
TI - The structure of the O2-N2O complex.
AB - We have investigated the lowest energy structures and interaction energies of the
oxygen nitrous oxide complex (O2-N2O) using explicitly correlated coupled cluster
theory. We find that the intermolecular potential energy surface of O2-N2O is
very flat, with two minima of comparable energy separated by a low energy first
order saddle point. Our results are able to conclusively distinguish between the
two sets of experimental geometric parameters for O2-N2O that were previously
determined from rotationally resolved infrared spectra. The global minimum
structure of O2-N2O is therefore found to be planar with a distorted slipped
parallel structure. Finally, we show that the very flat potential energy surface
of O2-N2O is problematic when evaluating vibrational frequencies with a numerical
Hessian and that consideration should be given as to whether results might change
if the step-size is varied.
PMID- 26429008
TI - Quantum free energy landscapes from ab initio path integral metadynamics: Double
proton transfer in the formic acid dimer is concerted but not correlated.
AB - With the goal of computing quantum free energy landscapes of reactive
(bio)chemical systems in multi-dimensional space, we combine the metadynamics
technique for sampling potential energy surfaces with the ab initio path integral
approach to treating nuclear quantum motion. This unified method is applied to
the double proton transfer process in the formic acid dimer (FAD), in order to
study the nuclear quantum effects at finite temperatures without imposing a one
dimensional reaction coordinate or reducing the dimensionality. Importantly, the
ab initio path integral metadynamics technique allows one to treat the hydrogen
bonds and concomitant proton transfers in FAD strictly independently and thus
provides direct access to the much discussed issue of whether the double proton
transfer proceeds via a stepwise or concerted mechanism. The quantum free energy
landscape we compute for this H-bonded molecular complex reveals that the two
protons move in a concerted fashion from initial to product state, yet world-line
analysis of the quantum correlations demonstrates that the protons are as quantum
uncorrelated at the transition state as they are when close to the equilibrium
structure.
PMID- 26429009
TI - Metal-ligand delocalization and spin density in the CuCl2 and [CuCl4](2-)
molecules: Some insights from wave function theory.
AB - The aim of this paper is to unravel the physical phenomena involved in the
calculation of the spin density of the CuCl2 and [CuCl4](2-) systems using wave
function methods. Various types of wave functions are used here, both variational
and perturbative, to analyse the effects impacting the spin density. It is found
that the spin density on the chlorine ligands strongly depends on the mixing
between two types of valence bond structures. It is demonstrated that the main
difficulties found in most of the previous studies based on wave function methods
come from the fact that each valence bond structure requires a different set of
molecular orbitals and that using a unique set of molecular orbitals in a
variational procedure leads to the removal of one of them from the wave function.
Starting from these results, a method to compute the spin density at a reasonable
computational cost is proposed.
PMID- 26429010
TI - Interatomic scattering in energy dependent photoelectron spectra of Ar clusters.
AB - Soft X-ray photoelectron spectra of Ar 2p levels of atomic argon and argon
clusters are recorded over an extended range of photon energies. The Ar 2p
intensity ratios between atomic argon and clusters' surface and bulk components
reveal oscillations similar to photoelectron extended X-ray absorption fine
structure signal (PEXAFS). We demonstrate here that this technique allows us to
analyze separately the PEXAFS signals from surface and bulk sites of free
standing, neutral clusters, revealing a bond contraction at the surface.
PMID- 26429011
TI - Observation and deperturbation of near-dissociation ro-vibrational structure of
the Cs2 state 0u(+) (A(1)Sigmau(+)~b(3)Pi0+u) at the asymptote 6S1/2 + 6P1/2.
AB - New ro-vibrational structures of cold Cs2 in the 0u(+) state near the asymptote
6S1/2 + 6P1/2 are resolved. The variation of the rotational constants shows that
the related energy spectra are strongly perturbed. An analysis of new data along
with the empirical and theoretical information available from other sources is
performed. For this purpose the model of spin-orbit coupling of the Hund's case
(a) states A(1)Sigmau(+)~b(3)Piu proposed by Bai et al. [Phys. Rev. A 83, 032514
(2011)] is extrapolated to the dissociation limit, and the parameters of the
extrapolation are fitted from the near-dissociation experimental data.
PMID- 26429012
TI - How large are nonadiabatic effects in atomic and diatomic systems?
AB - With recent developments in simulating nonadiabatic systems to high accuracy, it
has become possible to determine how much energy is attributed to nuclear quantum
effects beyond zero-point energy. In this work, we calculate the non-relativistic
ground-state energies of atomic and molecular systems without the Born
Oppenheimer approximation. For this purpose, we utilize the fixed-node diffusion
Monte Carlo method, in which the nodes depend on both the electronic and ionic
positions. We report ground-state energies for all systems studied, ionization
energies for the first-row atoms and atomization energies for the first-row
hydrides. We find the ionization energies of the atoms to be nearly independent
of the Born-Oppenheimer approximation, within the accuracy of our results. The
atomization energies of molecular systems, however, show small effects of the
nonadiabatic coupling between electrons and nuclei.
PMID- 26429013
TI - Photodissociation spectroscopy of the dysprosium monochloride molecular ion.
AB - We have performed a combined experimental and theoretical study of the
photodissociation cross section of the molecular ion DyCl(+). The
photodissociation cross section for the photon energy range 35,500 cm(-1) to
47,500 cm(-1) is measured using an integrated ion trap and time-of-flight mass
spectrometer; we observe a broad, asymmetric profile that is peaked near 43,000
cm(-1). The theoretical cross section is determined from electronic potentials
and transition dipole moments calculated using the relativistic configuration
interaction valence-bond and coupled-cluster methods. The electronic structure of
DyCl(+) is extremely complex due to the presence of multiple open electronic
shells, including the 4f(10) configuration. The molecule has nine attractive
potentials with ionically bonded electrons and 99 repulsive potentials
dissociating to a ground state Dy(+) ion and Cl atom. We explain the lack of
symmetry in the cross section as due to multiple contributions from one-electron
dominated transitions between the vibrational ground state and several resolved
repulsive excited states.
PMID- 26429014
TI - Structure, stability, and superconductivity of new Xe-H compounds under high
pressure.
AB - Application of high pressure can substantially enhance the chemical reactivity of
xenon and has recently extended the Xe-compounds to unexpected elements such as
Fe and H. Using unbiased structure searching techniques combined with first
principles calculations, we predict novel compounds of stable XeH2 and XeH4, and
metastable XeH, XeH3, XeH5, XeH6, XeH7, and XeH8 under high pressure. Rather than
van der Waals complexes, these are weakly covalent or ionic compounds stabilized
by a pressure-induced increase in charge transfer from Xe to H atoms. The
calculated electronic structures with hybrid exchange-correlation functionals
reveal that only XeH and XeH2 are metalized under 300 GPa. For the metallic XeH
and XeH2 at certain pressures, the superconducting critical temperatures are
finally studied, by using Allen-Dynes modified McMillan equation combined with
the calculated electron-phonon coupling parameter.
PMID- 26429015
TI - Microwave spectra and structure of the cyclopropanecarboxylic acid-formic acid
dimer.
AB - The rotational spectrum of the cyclopropanecarboxylic acid-formic acid doubly
hydrogen bonded dimer has been measured in the 4-11 GHz region using a Flygare
Balle type pulsed-beam Fourier transform microwave spectrometer. Rotational
transitions were measured for the parent, four unique singly substituted (13)C
isotopologues, and a singly deuterated isotopologue. Splittings due to a possible
concerted double proton tunneling motion were not observed. Rotational constants
(A, B, and C) and centrifugal distortion constants (DJ and DJK) were determined
from the measured transitions for the dimer. The values of the rotational (in
MHz) and centrifugal distortion constants (in kHz) for the parent isotopologue
are A = 4045.4193(16), B = 740.583 80(14), C = 658.567 60(23), DJ = 0.0499(16),
and DJK = 0.108(14). A partial gas phase structure of the dimer was derived from
the rotational constants of the measured isotopologues, previous structural work
on each monomer units and results of the calculations.
PMID- 26429016
TI - High reactivity of nanosized niobium oxide cluster cations in methane activation:
A comparison with vanadium oxides.
AB - The reactions between methane and niobium oxide cluster cations were studied and
compared to those employing vanadium oxides. Hydrogen atom abstraction (HAA)
reactions were identified over stoichiometric (Nb2O5)N(+) clusters for N as large
as 14 with a time-of-flight mass spectrometer. The reactivity of (Nb2O5)N(+)
clusters decreases as the N increases, and it is higher than that of (V 2O5)N(+)
for N >= 4. Theoretical studies were conducted on (Nb2O5)N(+) (N = 2-6) by
density functional calculations. HAA reactions on these clusters are all
favorable thermodynamically and kinetically. The difference of the reactivity
with respect to the cluster size and metal type (Nb vs V) was attributed to
thermodynamics, kinetics, the electron capture ability, and the distribution of
the unpaired spin density. Nanosized Nb oxide clusters show higher HAA reactivity
than V oxides, indicating that niobia may serve as promising catalysts for
practical methane conversion.
PMID- 26429017
TI - Line mixing in parallel and perpendicular bands of CO2: A further test of the
refined Robert-Bonamy formalism.
AB - Starting from the refined Robert-Bonamy formalism [Q. Ma, C. Boulet, and R. H.
Tipping, J. Chem. Phys. 139, 034305 (2013)], we propose here an extension of line
mixing studies to infrared absorptions of linear polyatomic molecules having
stretching and bending modes. The present formalism does not neglect the internal
degrees of freedom of the perturbing molecules, contrary to the energy corrected
sudden (ECS) modelling, and enables one to calculate the whole relaxation matrix
starting from the potential energy surface. Meanwhile, similar to the ECS
modelling, the present formalism properly accounts for roles played by all the
internal angular momenta in the coupling process, including the vibrational
angular momentum. The formalism has been applied to the important case of CO2
broadened by N2. Applications to two kinds of vibrational bands (Sigma -> Sigma
and Sigma -> Pi) have shown that the present results are in good agreement with
both experimental data and results derived from the ECS model.
PMID- 26429018
TI - Nucleation of liquid droplets and voids in a stretched Lennard-Jones fcc crystal.
AB - The method of molecular dynamics simulation has been used to investigate the
phase decay of a metastable Lennard-Jones face-centered cubic crystal at positive
and negative pressures. It is shown that at high degrees of metastability,
crystal decay proceeds through the spontaneous formation and growth of new-phase
nuclei. It has been found that there exists a certain boundary temperature. Below
this temperature, the crystal phase disintegrates as the result of formation of
voids, and above, as a result of formation of liquid droplets. The boundary
temperature corresponds to the temperature of cessation of a crystal-liquid phase
equilibrium when the melting line comes in contact with the spinodal of the
stretched liquid. The results of the simulations are interpreted in the framework
of classical nucleation theory. The thermodynamics of phase transitions in solids
has been examined with allowance for the elastic energy of stresses arising owing
to the difference in the densities of the initial and the forming phases. As a
result of the action of elastic forces, at negative pressures, the boundary of
the limiting superheating (stretching) of a crystal approaches the spinodal, on
which the isothermal bulk modulus of dilatation becomes equal to zero. At the
boundary of the limiting superheating (stretching), the shape of liquid droplets
and voids is close to the spherical one.
PMID- 26429019
TI - Pressure in the Landau-Ginzburg functional: Pascal's law, nucleation in fluid
mixtures, a meanfield theory of amphiphilic action, and interface wetting in
glassy liquids.
AB - We set up the problem of finding the transition state for phase nucleation in
multi-component fluid mixtures, within the Landau-Ginzburg density functional. We
establish an expression for the coordinate-dependent local pressure that applies
to mixtures, arbitrary geometries, and certain non-equilibrium configurations.
The expression allows one to explicitly evaluate the pressure in spherical
geometry, a la van der Waals. Pascal's law is recovered within the Landau
Ginzburg density functional theory, formally analogously to how conservation of
energy is recovered in the Lagrangian formulation of mechanics. We establish
proper boundary conditions for certain singular functional forms of the bulk free
energy density that allow one to obtain droplet solutions with thick walls in
essentially closed form. The hydrodynamic modes responsible for mixing near the
interface are explicitly identified in the treatment; the composition at the
interface is found to depend only weakly on the droplet size. Next we develop a
Landau-Ginzburg treatment of the effects of amphiphiles on the surface tension;
the amphiphilic action is seen as a violation of Pascal's law. We explicitly
obtain the binding potential for the detergent at the interface and the
dependence of the down-renormalization of the surface tension on the activity of
the detergent. Finally, we argue that the renormalization of the activation
barrier for escape from long-lived structures in glassy liquids can be viewed as
an action of uniformly seeded, randomly oriented amphiphilic molecules on the
interface separating two dissimilar aperiodic structures. This renormalization is
also considered as a "wetting" of the interface. The resulting conclusions are
consistent with the random first order transition theory.
PMID- 26429020
TI - Fluid-solid transition in simple systems using density functional theory.
AB - A free energy functional for a crystal which contains both the symmetry-conserved
and symmetry-broken parts of the direct pair correlation function has been used
to investigate the fluid-solid transition in systems interacting via purely
repulsive Weeks-Chandler-Anderson Lennard-Jones potential and the full Lennard
Jones potential. The results found for freezing parameters for the fluid-face
centred cubic crystal transition are in very good agreement with simulation
results. It is shown that although the contribution made by the symmetry broken
part to the grand thermodynamic potential at the freezing point is small compared
to that of the symmetry conserving part, its role is crucial in stabilizing the
crystalline structure and on values of the freezing parameters.
PMID- 26429021
TI - Ludwig-Soret effect of aqueous solutions of ethylene glycol oligomers, crown
ethers, and glycerol: Temperature, molecular weight, and hydrogen bond effect.
AB - The thermal diffusion, also called the Ludwig-Soret effect, of aqueous solutions
of ethylene glycol oligomers, crown ethers, and glycerol is investigated as a
function of temperature by thermal diffusion forced Rayleigh scattering. The
Soret coefficient, ST, and the thermal diffusion coefficient, DT, show a linear
temperature dependence for all studied compounds in the investigated temperature
range. The magnitudes and the slopes of ST and DT vary with the chemical
structure of the solute molecules. All studied molecules contain ether and/or
hydroxyl groups, which can act as acceptor or donor to form hydrogen bonds,
respectively. By introducing the number of donor and acceptor sites of each
solute molecule, we can express their hydrogen bond capability. ST and DT can be
described by an empirical equation depending on the difference of donor minus
acceptor sites and the molecular weight of the solute molecule.
PMID- 26429022
TI - Separation of experimental 2D IR frequency-frequency correlation functions into
structural and reorientation-induced contributions.
AB - A vibrational transition frequency can couple to its environment through a
directional vector interaction. In such cases, reorientation of the vibrational
transition dipole (molecular orientational relaxation) and its frequency
fluctuations can be strongly coupled. It was recently shown [Kramer et al., J.
Chem. Phys. 142, 184505 (2015)] that differing frequency-frequency correlation
function (FFCF) decays, due to reorientation-induced spectral diffusion (RISD),
are observed with different two-dimensional infrared polarization configurations
when such strong coupling is present. The FFC functional forms were derived for
the situation in which all spectral diffusion is due to reorientational motion.
We extend the previous theory to include vibrational frequency evolution
(spectral diffusion) caused by structural fluctuations of the medium. Model
systems with diffusive reorientation and several regimes of structural spectral
diffusion rates are analyzed for first order Stark effect interactions.
Additionally, the transition dipole reorientational motion in complex
environments is frequently not completely diffusive. Several periods of
restricted angular motion (wobbling-in-a-cone) may precede the final diffusive
orientational randomization. The polarization-weighted FFCF decays are presented
in this case of restricted transition dipole wobbling. With these extensions to
the polarization-dependent FFCF expressions, the structural spectral diffusion
dynamics of methanol in the room temperature ionic liquid 1-hexyl-3
methylimidazolium hexafluorophosphate can be separated quantitatively from RISD
using the experimental center line slope data. In addition, prior results on the
spectral diffusion of water, methanol, and ethanol in 1-ethyl-3-methylimidazolium
bis(trifluoromethylsulfonyl)imide are re-examined to elucidate the influence of
reorientation on the data, which were interpreted in terms of structural
fluctuations.
PMID- 26429023
TI - Molecular simulation of homogeneous nucleation of crystals of an ionic liquid
from the melt.
AB - The homogeneous nucleation of crystals of the ionic liquid [dmim(+)][Cl(-)] from
its supercooled liquid phase in the bulk (P = 1 bar, T = 340 K, representing a
supercooling of 58 K) was studied using molecular simulations. The string method
in collective variables [Maragliano et al., J. Chem. Phys. 125, 024106 (2006)]
was used in combination with Markovian milestoning with Voronoi tessellations
[Maragliano et al., J. Chem. Theory Comput. 5, 2589-2594 (2009)] and order
parameters for molecular crystals [E. E. Santiso and B. L. Trout, J. Chem. Phys.
134, 064109 (2011)] to sketch a minimum free energy path connecting the
supercooled liquid and the monoclinic crystal phases, and to determine the free
energy and the rates involved in the homogeneous nucleation process. The physical
significance of the configurations found along this minimum free energy path is
discussed with the help of calculations based on classical nucleation theory and
with additional simulation results obtained for a larger system. Our results
indicate that, at a supercooling of 58 K, the liquid has to overcome a free
energy barrier of the order of 60 kcal/mol and to form a critical nucleus with an
average size of about 3.6 nm, before it reaches the thermodynamically stable
crystal phase. A simulated homogeneous nucleation rate of 5.0 * 10(10) cm(-3) s(
1) was obtained for our system, which is in reasonable agreement with
experimental and simulation rates for homogeneous nucleation of ice at similar
degrees of supercooling. This study represents our first step in a series of
studies aimed at understanding the nucleation and growth of crystals of organic
salts near surfaces and inside nanopores.
PMID- 26429024
TI - Molecular dynamics simulations of the structure and single-particle dynamics of
mixtures of divalent salts and ionic liquids.
AB - We report a molecular dynamics study of the structure and single-particle
dynamics of mixtures of a protic (ethylammonium nitrate) and an aprotic (1-butyl
3-methylimidazolium hexaflurophosphate [BMIM][PF6]) room-temperature ionic
liquids doped with magnesium and calcium salts with a common anion at 298.15 K
and 1 atm. The solvation of these divalent cations in dense ionic environments is
analyzed by means of apparent molar volumes of the mixtures, radial distribution
functions, and coordination numbers. For the protic mixtures, the effect of salt
concentration on the network of hydrogen bonds is also considered. Moreover,
single-particle dynamics of the salt cations is studied by means of their
velocity autocorrelation functions and vibrational densities of states,
explicitly analyzing the influence of salt concentration, and cation charge and
mass on these magnitudes. The effect of the valency of the salt cation on these
properties is considered comparing the results with those for the corresponding
mixtures with lithium salts. We found that the main structural and dynamic
features of the local solvation of divalent cations in ionic liquids are similar
to those of monovalent salts, with cations being localized in the polar
nanoregions of the bulk mixture coordinated in monodentate and bidentate
coordination modes by the [NO3](-) and [PF6](-) anions. However, stronger
electrostatic correlations of these polar nanoregions than in mixtures with salts
with monovalent cations are found. The vibrational modes of the ionic liquid (IL)
are seen to be scarcely affected by the addition of the salt, and the effect of
mass and charge on the vibrational densities of states of the dissolved cations
is reported. Cation mass is seen to exert a deeper influence than charge on the
low-frequency vibrational spectra, giving a red shift of the vibrational modes
and a virtual suppression of the higher energy vibrational modes for the heavier
Ca(2+) cations. No qualitative difference with monovalent cations was found in
what solvation is concerned, which suggests that no enhanced reduction of the
mobility of these cations and their complexes in ILs respective to those of
monovalent cations is to be expected.
PMID- 26429025
TI - A first-principle calculation of the XANES spectrum of Cu(2+) in water.
AB - The progress in high performance computing we are witnessing today offers the
possibility of accurate electron density calculations of systems in realistic
physico-chemical conditions. In this paper, we present a strategy aimed at
performing a first-principle computation of the low energy part of the X-ray
Absorption Spectroscopy (XAS) spectrum based on the density functional theory
calculation of the electronic potential. To test its effectiveness, we apply the
method to the computation of the X-ray absorption near edge structure part of the
XAS spectrum in the paradigmatic, but simple case of Cu(2+) in water. In order to
keep into account the effect of the metal site structure fluctuations in
determining the experimental signal, the theoretical spectrum is evaluated as the
average over the computed spectra of a statistically significant number of
simulated metal site configurations. The comparison of experimental data with
theoretical calculations suggests that Cu(2+) lives preferentially in a square
pyramidal geometry. The remarkable success of this approach in the interpretation
of XAS data makes us optimistic about the possibility of extending the
computational strategy we have outlined to the more interesting case of molecules
of biological relevance bound to transition metal ions.
PMID- 26429026
TI - Double-walled carbon nanotube array for CO2 and SO2 adsorption.
AB - Grand-canonical Monte Carlo simulations and adsorption experiments are combined
to find the optimized carbon nanotube (CNT) arrays for gas adsorption at low
pressures and 303 K. Bundles of 3D aligned double-walled carbon nanotube (DWCNT)
with inner diameter of 8 nm and different intertube distances were made
experimentally. The experimental results show that decreasing intertube distance
leads to a significant enhancement in carbon-dioxide (CO2) adsorption capacity at
1 bar. The molecular simulation study on CO2 adsorption onto bundles of 3D
aligned DWCNT with inner diameters of 1, 3, and 8 nm and intertube distance of 0
15 nm shows that the intertube distance plays a more important role than the CNT
diameter. The simulation results show that decreasing the intertube distance up
to 1 nm increases the excess adsorption generally in all the studied systems at
pressures 0 < p < 14 bars (the increase can be up to ~40% depending on the system
and pressure). This is in agreement with the experimental result. Further
reduction in intertube distance leads to a decrease in the excess adsorption in
the pressure range 9 < p < 14 bars. However, at lower pressure, 0 < p < 9 bars,
intertube distance of 0.5 nm is found to have the highest excess adsorption. This
result is indifferent to tube diameter. Furthermore, molecular simulations are
conducted to obtain the optimal parameters, for the DWCNT bundle, for SO2
adsorption, which are similar to those observed for CO2 in the pressure range 0 <
p < 3 bars.
PMID- 26429027
TI - Toward ab initio molecular dynamics modeling for sum-frequency generation
spectra; an efficient algorithm based on surface-specific velocity-velocity
correlation function.
AB - Interfacial water structures have been studied intensively by probing the O-H
stretch mode of water molecules using sum-frequency generation (SFG)
spectroscopy. This surface-specific technique is finding increasingly widespread
use, and accordingly, computational approaches to calculate SFG spectra using
molecular dynamics (MD) trajectories of interfacial water molecules have been
developed and employed to correlate specific spectral signatures with distinct
interfacial water structures. Such simulations typically require relatively long
(several nanoseconds) MD trajectories to allow reliable calculation of the SFG
response functions through the dipole moment-polarizability time correlation
function. These long trajectories limit the use of computationally expensive MD
techniques such as ab initio MD and centroid MD simulations. Here, we present an
efficient algorithm determining the SFG response from the surface-specific
velocity-velocity correlation function (ssVVCF). This ssVVCF formalism allows us
to calculate SFG spectra using a MD trajectory of only ~100 ps, resulting in the
substantial reduction of the computational costs, by almost an order of
magnitude. We demonstrate that the O-H stretch SFG spectra at the water-air
interface calculated by using the ssVVCF formalism well reproduce those
calculated by using the dipole moment-polarizability time correlation function.
Furthermore, we applied this ssVVCF technique for computing the SFG spectra from
the ab initio MD trajectories with various density functionals. We report that
the SFG responses computed from both ab initio MD simulations and MD simulations
with an ab initio based force field model do not show a positive feature in its
imaginary component at 3100 cm(-1).
PMID- 26429028
TI - Quantum dynamics of hydrogen atoms on graphene. I. System-bath modeling.
AB - An accurate system-bath model to investigate the quantum dynamics of hydrogen
atoms chemisorbed on graphene is presented. The system comprises a hydrogen atom
and the carbon atom from graphene that forms the covalent bond, and it is
described by a previously developed 4D potential energy surface based on density
functional theory ab initio data. The bath describes the rest of the carbon
lattice and is obtained from an empirical force field through inversion of a
classical equilibrium correlation function describing the hydrogen motion. By
construction, model building easily accommodates improvements coming from the use
of higher level electronic structure theory for the system. Further, it is well
suited to a determination of the system-environment coupling by means of ab
initio molecular dynamics. This paper details the system-bath modeling and shows
its application to the quantum dynamics of vibrational relaxation of a
chemisorbed hydrogen atom, which is here investigated at T = 0 K with the help of
the multi-configuration time-dependent Hartree method. Paper II deals with the
sticking dynamics.
PMID- 26429029
TI - Quantum dynamics of hydrogen atoms on graphene. II. Sticking.
AB - Following our recent system-bath modeling of the interaction between a hydrogen
atom and a graphene surface [Bonfanti et al., J. Chem. Phys. 143, 124703 (2015)],
we present the results of converged quantum scattering calculations on the
activated sticking dynamics. The focus of this study is the collinear scattering
on a surface at zero temperature, which is treated with high-dimensional
wavepacket propagations with the multi-configuration time-dependent Hartree
method. At low collision energies, barrier-crossing dominates the sticking and
any projectile that overcomes the barrier gets trapped in the chemisorption well.
However, at high collision energies, energy transfer to the surface is a limiting
factor, and fast H atoms hardly dissipate their excess energy and stick on the
surface. As a consequence, the sticking coefficient is maximum (~0.65) at an
energy which is about one and half larger than the barrier height. Comparison of
the results with classical and quasi-classical calculations shows that quantum
fluctuations of the lattice play a primary role in the dynamics. A simple
impulsive model describing the collision of a classical projectile with a quantum
surface is developed which reproduces the quantum results remarkably well for all
but the lowest energies, thereby capturing the essential physics of the activated
sticking dynamics investigated.
PMID- 26429030
TI - Vibrational dynamics and band structure of methyl-terminated Ge(111).
AB - A combined synthesis, experiment, and theory approach, using elastic and
inelastic helium atom scattering along with ab initio density functional
perturbation theory, has been used to investigate the vibrational dynamics and
band structure of a recently synthesized organic-functionalized semiconductor
interface. Specifically, the thermal properties and lattice dynamics of the
underlying Ge(111) semiconductor crystal in the presence of a commensurate (1 *
1) methyl adlayer were defined for atomically flat methylated Ge(111) surfaces.
The mean-square atomic displacements were evaluated by analysis of the thermal
attenuation of the elastic He diffraction intensities using the Debye-Waller
model, revealing an interface with hybrid characteristics. The methyl adlayer
vibrational modes are coupled with the Ge(111) substrate, resulting in
significantly softer in-plane motion relative to rigid motion in the surface
normal. Inelastic helium time-of-flight measurements revealed the excitations of
the Rayleigh wave across the surface Brillouin zone, and such measurements were
in agreement with the dispersion curves that were produced using density
functional perturbation theory. The dispersion relations for H-Ge(111) indicated
that a deviation in energy and lineshape for the Rayleigh wave was present along
the nearest-neighbor direction. The effects of mass loading, as determined by
calculations for CD3-Ge(111), as well as by force constants, were less
significant than the hybridization between the Rayleigh wave and methyl adlayer
librations. The presence of mutually similar hybridization effects for CH3
Ge(111) and CH3-Si(111) surfaces extends the understanding of the relationship
between the vibrational dynamics and the band structure of various semiconductor
surfaces that have been functionalized with organic overlayers.
PMID- 26429031
TI - Sustained magnetization oscillations in polyaniline-Fe3O4 nanocomposites.
AB - We report experiments with polyaniline-Fe3O4 (PANI-Fe3O4) nanocomposites
synthesized under several different conditions. With a reaction carried out at
room temperature and assisted by intense ultra-violet (UV) irradiation, we
observe sustained oscillations in the magnetization with a period of about 25
min. The oscillations are interpreted as the result of an oscillatory chemical
reaction in which part of the Fe(+2) ions of magnetite, Fe3O4, are oxidized by
the UV irradiation to form Fe(+3) so that a fraction of the magnetite content
transforms into maghemite, gamma-Fe2O3. Then, Fe(+3) ions at the nanoparticle
surfaces are reduced and transformed back into Fe(+2), when acting as an
oxidizing agent for polyaniline in the polymerization process. Since maghemite
has smaller magnetization than magnetite, the oscillating chemical reaction
results in the oscillatory magnetization. The observations are interpreted with
the Lotka-Volterra nonlinear coupled equations with parameters that can be
adjusted to fit very well the experimental data.
PMID- 26429032
TI - Accurate determination of complex chi(2) spectrum of the air/water interface.
AB - Discussion on the structure of the water surface relies on accurate determination
of the chi(2) spectrum. For obtaining accurate chi(2) spectrum of the air/water
interface in the OH stretch region, we performed heterodyne-detected vibrational
sum-frequency generation measurements with a high phase accuracy, and also
examined the validity of the phase and amplitude calibration using different non
resonant materials. In contrast to the previous reports, it was concluded that
the imaginary part of the chi(2) spectrum of the air/water interface does not
exhibit noticeable positive resonance in the low frequency region within the
experimental error. This result urges us to reconsider the structure of the
air/water interface based on the accurate chi(2) spectrum.
PMID- 26429033
TI - An accurate full-dimensional potential energy surface for H-Au(111): Importance
of nonadiabatic electronic excitation in energy transfer and adsorption.
AB - We have constructed a potential energy surface (PES) for H-atoms interacting with
fcc Au(111) based on fitting the analytic form of the energy from Effective
Medium Theory (EMT) to ab initio energy values calculated with density functional
theory. The fit used input from configurations of the H-Au system with Au atoms
at their lattice positions as well as configurations with the Au atoms displaced
from their lattice positions. It reproduces the energy, in full dimension, not
only for the configurations used as input but also for a large number of
additional configurations derived from ab initio molecular dynamics (AIMD)
trajectories at finite temperature. Adiabatic molecular dynamics simulations on
this PES reproduce the energy loss behavior of AIMD. EMT also provides
expressions for the embedding electron density, which enabled us to develop a
self-consistent approach to simulate nonadiabatic electron-hole pair excitation
and their effect on the motion of the incident H-atoms. For H atoms with an
energy of 2.7 eV colliding with Au, electron-hole pair excitation is by far the
most important energy loss pathway, giving an average energy loss ~3 times that
of the adiabatic case. This increased energy loss enhances the probability of the
H-atom remaining on or in the Au slab by a factor of 2. The most likely outcome
for H-atoms that are not scattered also depends prodigiously on the energy
transfer mechanism; for the nonadiabatic case, more than 50% of the H-atoms which
do not scatter are adsorbed on the surface, while for the adiabatic case more
than 50% pass entirely through the 4 layer simulation slab.
PMID- 26429034
TI - Probing protein orientation near charged nanosurfaces for simulation-assisted
biosensor design.
AB - Protein-surface interactions are ubiquitous in biological processes and
bioengineering, yet are not fully understood. In biosensors, a key factor
determining the sensitivity and thus the performance of the device is the
orientation of the ligand molecules on the bioactive device surface. Adsorption
studies thus seek to determine how orientation can be influenced by surface
preparation, varying surface charge, and ambient salt concentration. In this
work, protein orientation near charged nanosurfaces is obtained under
electrostatic effects using the Poisson-Boltzmann equation, in an implicit
solvent model. Sampling the free energy for protein G B1 D4' at a range of tilt
and rotation angles with respect to the charged surface, we calculated the
probability of the protein orientations and observed a dipolar behavior. This
result is consistent with published experimental studies and combined Monte Carlo
and molecular dynamics simulations using this small protein, validating our
method. More relevant to biosensor technology, antibodies such as immunoglobulin
G are still a formidable challenge to molecular simulation, due to their large
size. With the Poisson-Boltzmann model, we obtained the probability distribution
of orientations for the iso-type IgG2a at varying surface charge and salt
concentration. This iso-type was not found to have a preferred orientation in
previous studies, unlike the iso-type IgG1 whose larger dipole moment was assumed
to make it easier to control. Our results show that the preferred orientation of
IgG2a can be favorable for biosensing with positive charge on the surface of 0.05
C/m(2) or higher and 37 mM salt concentration. The results also show that local
interactions dominate over dipole moment for this protein. Improving immunoassay
sensitivity may thus be assisted by numerical studies using our method (and open
source code), guiding changes to fabrication protocols or protein engineering of
ligand molecules to obtain more favorable orientations.
PMID- 26429035
TI - Rayleigh-type parametric chemical oscillation.
AB - We consider a nonlinear chemical dynamical system of two phase space variables in
a stable steady state. When the system is driven by a time-dependent sinusoidal
forcing of a suitable scaling parameter at a frequency twice the output frequency
and the strength of perturbation exceeds a threshold, the system undergoes
sustained Rayleigh-type periodic oscillation, wellknown for parametric
oscillation in pipe organs and distinct from the usual forced quasiperiodic
oscillation of a damped nonlinear system where the system is oscillatory even in
absence of any external forcing. Our theoretical analysis of the parametric
chemical oscillation is corroborated by full numerical simulation of two well
known models of chemical dynamics, chlorite-iodine-malonic acid and iodine-clock
reactions.
PMID- 26429036
TI - Relaxation times and modes of disturbed aggregate distribution in micellar
solutions with fusion and fission of micelles.
AB - We have performed direct numerical calculations of the kinetics of relaxation in
the system of surfactant spherical micelles under joint action of the molecular
mechanism with capture and emission of individual surfactant molecules by
molecular aggregates and the mechanism of fusion and fission of the aggregates.
As a basis, we have taken the difference equations of aggregation and
fragmentation in the form of the generalized kinetic Smoluchowski equations for
aggregate concentrations. The calculations have been made with using the droplet
model of molecular surfactant aggregates and two modified Smoluchowski models for
the coefficients of aggregate-monomer and aggregate-aggregate fusions which take
into account the effects of the aggregate size and presence of hydrophobic spots
on the aggregate surface. A full set of relaxation times and corresponding
relaxation modes for nonequilibrium aggregate distribution in the aggregation
number has been found. The dependencies of these relaxation times and modes on
the total concentration of surfactant in the solution and the special parameter
controlling the probability of fusion in collisions of micelles with other
micelles have been studied.
PMID- 26429037
TI - Persistent draining crossover in DNA and other semi-flexible polymers: Evidence
from hydrodynamic models and extensive measurements on DNA solutions.
AB - Although the scaling theory of polymer solutions has had many successes, this
type of argument is deficient when applied to hydrodynamic solution properties.
Since the foundation of polymer science, it has been appreciated that
measurements of polymer size from diffusivity, sedimentation, and solution
viscosity reflect a convolution of effects relating to polymer geometry and the
strength of the hydrodynamic interactions within the polymer coil, i.e.,
"draining." Specifically, when polymers are expanded either by self-excluded
volume interactions or inherent chain stiffness, the hydrodynamic interactions
within the coil become weaker. This means there is no general relationship
between static and hydrodynamic size measurements, e.g., the radius of gyration
and the hydrodynamic radius. We study this problem by examining the hydrodynamic
properties of duplex DNA in solution over a wide range of molecular masses both
by hydrodynamic modeling using a numerical path-integration method and by
comparing with extensive experimental observations. We also considered how
excluded volume interactions influence the solution properties of DNA and confirm
that excluded volume interactions are rather weak in duplex DNA in solution so
that the simple worm-like chain model without excluded volume gives a good
leading-order description of DNA for molar masses up to 10(7) or 10(8) g/mol or
contour lengths between 5 MUm and 50 MUm. Since draining must also depend on the
detailed chain monomer structure, future work aiming to characterize polymers in
solution through hydrodynamic measurements will have to more carefully consider
the relation between chain molecular structure and hydrodynamic solution
properties. In particular, scaling theory is inadequate for quantitative polymer
characterization.
PMID- 26429038
TI - Dynamics of flexible fibers in shear flow.
AB - Dynamics of flexible non-Brownian fibers in shear flow at low-Reynolds-number are
analyzed numerically for a wide range of the ratios A of the fiber bending force
to the viscous drag force. Initially, the fibers are aligned with the flow, and
later they move in the plane perpendicular to the flow vorticity. A surprisingly
rich spectrum of different modes is observed when the value of A is
systematically changed, with sharp transitions between coiled and straightening
out modes, period-doubling bifurcations from periodic to migrating solutions,
irregular dynamics, and chaos.
PMID- 26429039
TI - Solvent controlled ion association in structured copolymers: Molecular dynamics
simulations in dilute solutions.
AB - Tailoring the nature of individual segments within ion containing block co
polymers is one critical design tool to achieve desired properties. The local
structure including the size and distribution of the ionic blocks, as well as the
long range correlations, are crucial for their transport ability. Here, we
present molecular dynamics simulations on the effects of varying the
concentrations of the ionizable groups on the conformations of pentablock ionomer
that consist of a center block of ionic sulfonated styrene tethered to
polyethylene and terminated by a bulky substituted styrene in dilute solutions.
Sulfonation fractions f (0 <= f <= 0.55), spanning the range from ionomer to
polyelectrolytes, were studied. Results for the equilibrium conformation of the
chains in water and a 1:1 mixture of cyclohexane and heptane are compared to that
in implicit poor solvents with dielectric constants epsilon = 1.0 and 77.73. In
water, the pentablock collapses with the sulfonated groups on the outer surface.
As f increases, the ionic, center block increasingly segregates from the
hydrophobic regions. In the 1:1 mixture of cyclohexane and heptane, the flexible
blocks swell, while the center ionic block collapses for f > 0. For f = 0, all
blocks swell. In both implicit poor solvents, the pentablock collapses into a
nearly spherical shape for all f. The sodium counterions disperse widely
throughout the simulation cell for both water and epsilon = 77.73, whereas for
epsilon = 1.0 and mixture of cyclohexane and heptane, the counterions largely
condense onto the collapsed pentablock.
PMID- 26429040
TI - Perturbation theory for multicomponent fluids based on structural properties of
hard-sphere chain mixtures.
AB - An analytical expression for the Laplace transform of the radial distribution
function of a mixture of hard-sphere chains of arbitrary segment size and chain
length is used to rigorously formulate the first-order Barker-Henderson
perturbation theory for the contribution of the segment-segment dispersive
interactions into thermodynamics of the Lennard-Jones chain mixtures. Based on
this approximation, a simple variant of the statistical associating fluid theory
is proposed and used to predict properties of several mixtures of chains of
different lengths and segment sizes. The theory treats the dispersive
interactions more rigorously than the conventional theories and provides means
for more accurate description of dispersive interactions in the mixtures of
highly asymmetric components.
PMID- 26429041
TI - Unraveling the luminescence signatures of chemical defects in polyethylene.
AB - Chemical defects in polyethylene (PE) can deleteriously downgrade its electrical
properties and performance. Although these defects usually leave spectroscopic
signatures in terms of characteristic luminescence peaks, it is nontrivial to
make unambiguous assignments of the peaks to specific defect types. In this work,
we go beyond traditional density functional theory calculations to determine
intra-defect state transition and charge recombination process derived emission
and absorption energies in PE. By calculating the total energy differences of the
neutral defect at excited and ground states, the emission energies from intra
defect state transition are obtained, reasonably explaining the photoluminescence
peaks in PE. In order to study the luminescence emitted in charge recombination
processes, we characterize PE defect levels in terms of thermodynamic and optical
charge transition levels that involve total energy calculations of neutral and
charged defects. Calculations are performed at several levels of theory including
those involving (semi)local and hybrid electron exchange-correlation functionals,
and many-body perturbation theory. With these critical elements, the emission
energies are computed and further used to clarify and confirm the origins of the
observed electroluminescence and thermoluminescence peaks.
PMID- 26429042
TI - beta-sheet-like formation during the mechanical unfolding of prion protein.
AB - Single molecule experiments and simulations have been widely used to characterize
the unfolding and folding pathways of different proteins. However, with few
exceptions, these tools have not been applied to study prion protein, PrP(C),
whose misfolded form PrP(Sc) can induce a group of fatal neurodegenerative
diseases. Here, we apply novel atomistic modeling based on potential energy
surface exploration to study the constant force unfolding of human PrP at time
scales inaccessible with standard molecular dynamics. We demonstrate for forces
around 100 pN, prion forms a stable, three-stranded beta-sheet-like intermediate
configuration containing residues 155-214 with a lifetime exceeding hundreds of
nanoseconds. A mutant without the disulfide bridge shows lower stability during
the unfolding process but still forms the three-stranded structure. The
simulations thus not only show the atomistic details of the mechanically induced
structural conversion from the native alpha-helical structure to the beta-rich
like form but also lend support to the structural theory that there is a core of
the recombinant PrP amyloid, a misfolded form reported to induce transmissible
disease, mapping to C-terminal residues ~160-220.
PMID- 26429043
TI - On the physics of thermal-stability changes upon mutations of a protein.
AB - It is of great interest from both scientific and practical viewpoints to
theoretically predict the thermal-stability changes upon mutations of a protein.
However, such a prediction is an intricate task. Up to now, significantly many
approaches for the prediction have been reported in the literature. They always
include parameters which are adjusted so that the prediction results can be best
fitted to the experimental data for a sufficiently large set of proteins and
mutations. The inclusion is necessitated to achieve satisfactorily high
prediction performance. A problem is that the resulting values of the parameters
are often physically meaningless, and the physicochemical factors governing the
thermal-stability changes upon mutations are rather ambiguous. Here, we develop a
new measure of the thermal stability. Protein folding is accompanied by a large
gain of water entropy (the entropic excluded-volume (EV) effect), loss of protein
conformational entropy, and increase in enthalpy. The enthalpy increase
originates primarily from the following: The energy increase due to the break of
protein-water hydrogen bonds (HBs) upon folding cannot completely be cancelled
out by the energy decrease brought by the formation of protein intramolecular
HBs. We develop the measure on the basis of only these three factors and apply it
to the prediction of the thermal-stability changes upon mutations. As a
consequence, an approach toward the prediction is obtained. It is distinguished
from the previously reported approaches in the following respects: The parameters
adjusted in the manner mentioned above are not employed at all, and the entropic
EV effect, which is ascribed to the translational displacement of water molecules
coexisting with the protein in the system, is fully taken into account using a
molecular model for water. Our approach is compared with one of the most popular
approaches, FOLD-X, in terms of the prediction performance not only for single
mutations but also for double, triple, and higher-fold (up to sevenfold)
mutations. It is shown that on the whole our approach and FOLD-X exhibit almost
the same performance despite that the latter uses the adjusting parameters. For
multiple mutations, however, our approach is far superior to FOLD-X. Five
multiple mutations for staphylococcal nuclease lead to highly enhanced
stabilities, but we find that this high enhancement arises from the entropic EV
effect. The neglect of this effect in FOLD-X is a principal reason for its ill
success. A conclusion is that the three factors mentioned above play essential
roles in elucidating the thermal-stability changes upon mutations.
PMID- 26429044
TI - Ionic liquid induced dehydration and domain closure in lysozyme: FCS and MD
simulation.
AB - Effect of a room temperature ionic liquid (RTIL, [pmim][Br]) on the structure and
dynamics of the protein, lysozyme, is investigated by fluorescence correlation
spectroscopy (FCS) and molecular dynamic (MD) simulation. The FCS data indicate
that addition of the RTIL ([pmim][Br]) leads to reduction in size and faster
conformational dynamics of the protein. The hydrodynamic radius (rH) of lysozyme
decreases from 18 A in 0 M [pmim][Br] to 11 A in 1.5 M [pmim][Br] while the
conformational relaxation time decreases from 65 MUs to 5 MUs. Molecular origin
of the collapse (size reduction) of lysozyme in aqueous RTIL is analyzed by MD
simulation. The radial distribution function of water, RTIL cation, and RTIL
anion from protein clearly indicates that addition of RTIL causes replacement of
interfacial water by RTIL cation ([pmim](+)) from the first solvation layer of
the protein providing a comparatively dehydrated environment. This preferential
solvation of the protein by the RTIL cation extends up to ~30 A from the protein
surface giving rise to a nanoscopic cage of overall radius 42 A. In the
nanoscopic cage of the RTIL (42 A), volume fraction of the protein (radius 12 A)
is only about 2%. RTIL anion does not show any preferential solvation near
protein surface. Comparison of effective radius obtained from simulation and from
FCS data suggests that the "dry" protein (radius 12 A) alone diffuses in a
nanoscopic cage of RTIL (radius 42 A). MD simulation further reveals a decrease
in distance ("domain closure") between the two domains (alpha and beta) of the
protein leading to a more compact structure compared to that in the native state.
PMID- 26429045
TI - Publisher's Note: "Anisotropic time-resolved solution X-ray scattering patterns
from explicit-solvent molecular dynamics" [J. Chem. Phys. 143, 104108 (2015)].
PMID- 26429046
TI - Publisher's Note: "Assignment of the vibrations of the S0, S1, and D0(+) states
of perhydrogenated and perdeuterated isotopologues of chlorobenzene" [J. Chem.
Phys. 143, 104312 (2015)].
PMID- 26429047
TI - Erratum: "Stochastic many-body perturbation theory for anharmonic molecular
vibrations" [J. Chem. Phys. 141, 084105 (2014)].
PMID- 26429048
TI - Erratum: "Stochastic algorithm for size-extensive vibrational self-consistent
field methods on fully anharmonic potential energy surfaces" [J. Chem. Phys. 141,
244111 (2014)].
PMID- 26429049
TI - Laparoscopy Combined With Transanal Endoscopic Microsurgery for Rectal Cancer: A
Prospective, Single-blinded, Randomized Clinical Trial.
AB - OBJECTIVE: To evaluate the efficacy of laparoscopy combined with transanal
endoscopic microsurgery (TEM) in the treatment of rectal cancer. METHODS: A total
of 60 rectal cancer patients who underwent radical resection from December 2009
to December 2013 were enrolled in this study. All patients were randomly divided
to receive either laparoscopic surgery (LA group) or laparoscopy combined with
TEM (LT group). Demographics including age and sex, and tumor characteristics
including tumor size, distance from anal verge, and preoperative staging were all
recorded. The operation time, hospital stay, cases with intraoperative blood
transfusion, the number of resected lymph node, postoperative out-of-bed
activity, passage of gas by anus, fasting time, and postoperative complications
were assessed. RESULTS: Compared with the LA group, patients in the LT group had
shorter operation time (118.5+/-22.0 vs. 138.1+/-23.8 min, P=0.002), earlier out
of-bed activity (60.4+/-19.2 vs. 83.6+/-9.6 h, P=0.001) and passage of gas by
anus (81.4+/-5.4 vs. 86.2+/-8.7 h, P=0.013), and shorter hospital stay (8.0+/-2.8
vs. 11.0+/-3.5 d, P=0.001). Patients were followed up for a median time of 28
months (range, 3 to 48 mo). No local recurrence and distant metastasis occurred
in all cases. CONCLUSIONS: Laparoscopy combined with TEM is a feasible and
effective treatment for radical excision of middle-upper rectal cancer due to the
advantages of lower morbidity and earlier recovery.
PMID- 26429050
TI - Evaluation and Comparison of the Early Outcomes of Open and Laparoscopic Surgery
of Liver Hydatid Cyst.
AB - BACKGROUND AND AIM: Surgery is the mainstay for treatment of liver hydatid cyst.
Different surgical procedures have been suggested, but it is important to select
the most appropriate treatment to obtain the best results with the lowest rate of
recurrence and minimal morbidity and mortality. The aim of this study was to
evaluate the early outcomes of open and laparoscopic surgery of hydatidosis.
MATERIALS AND METHODS: In this study, 75 patients with uncomplicated liver
hydatid cyst were assigned prospectively to either groups of laparoscopic surgery
(37, 50.68%) or open procedure (36, 49.32%) during the period of 2007 to 2012.
Conversion to open surgery was required in 2 patients (2.67%), who were excluded
from the study. Patients were followed for about 17.86+/-17.64 months. RESULTS:
Participants included 73 patients: 49 (67.12%) female and 24 (32.88%) male
patients, with the mean age of 38.97+/-16.48 years. There was no statistically
significant difference between the 2 groups with regard to the sex, the
occupation, and the mean diameter of the cysts. Bilious staining of the cyst
content was observed in 23 (35.94%) patients during surgery, and a maximum
diameter of 91 mm was considered as a cut point for predicting postoperative
fistula with 69.2% sensitivity and 41.1% specificity. The mean duration of
operation, postoperative pain, the hospitalization time, and the time to return
to work were significantly lower in the laparoscopic group. Postoperative biliary
fistula, cyst cavity infection, and wound infection were not different between
the 2 groups. CONCLUSIONS: Laparoscopic surgery seems to be effective and safe,
with low morbidity rates for uncomplicated cysts in accessible segments of the
liver.
PMID- 26429051
TI - Per-Oral Endoscopic Myotomy (POEM) After Previous Laparoscopic Heller Myotomy Is
Feasible and Safe in a Porcine Model.
AB - PURPOSE: We sought to evaluate the feasibility, safety, and difficulty of
performing the per-oral endoscopic myotomy (POEM) procedure in the setting of a
prior Heller myotomy using a survival porcine model. METHODS: Four pigs underwent
laparoscopic Heller myotomy with Dor partial anterior fundoplication followed by
the POEM performed 4 weeks later. Two additional pigs served as controls,
undergoing only the POEM. RESULTS: All procedures were completed without
complications. The revisional POEM was not significantly more difficult than POEM
controls based on procedure time, POEM procedure components, or procedure
difficulty scores. Revisional POEM had a longer mean operative time when compared
with Heller myotomy (126.0 vs. 83.8 min; P<0.01) but had a lower total difficulty
score (28.6 vs. 52.1; P?0.01). CONCLUSIONS: A POEM after previous Heller myotomy
is safe and feasible in the porcine model and has potential as an option for
patients suffering from recurrent or persistent symptoms after failed surgical
myotomy.
PMID- 26429052
TI - The Survival and Complication Rates of Laparoscopic Versus Open Catheter
Placement in Peritoneal Dialysis Patients: A Meta-Analysis.
AB - The objective of this meta-analysis was to compare the outcomes of laparoscopic
insertion method with a conventional open surgery. A systematical search was
conducted in PubMed, Embase, and the Cochrane Library up to June 2014. Relative
risks (RRs) and their 95% confidence intervals (CIs) were used as estimates. Four
randomized-controlled trials and 10 cohort studies involving 2323 patients were
identified. The pooled results showed that laparoscopic insertion technique
significantly prolonged the 1-year survival (RR=1.23; 95% CI, 1.12-1.35) and 2
year survival (RR=1.36; 95% CI, 1.16-1.60). Meanwhile, laparoscopic insertion
significantly decreased the probability of surgical intervention or catheter
revision (RR=0.32; 95% CI, 0.15-0.69) and risk of migration (RR=0.31; 95% CI,
0.18-0.53) and obstruction (RR=0.43; 95% CI, 0.28-0.66). Thus, laparoscopic
catheter placement may be superior to open surgery in peritoneal dialysis
catheter placement.
PMID- 26429053
TI - Open Surgery Against Laparoscopic Surgery for Mid-Rectal or Low-Rectal Cancer of
Male Patients: Better Postoperative Genital Function of Laparoscopic Surgery.
AB - PURPOSE: To evaluate retrospectively the postoperative genital function, the
local recurrence, and the survival rate impacted by laparoscopic or open surgery
for rectal cancer (RC) in male patients. METHODS: A total of 398 male RC patients
after laparoscopic or open total mesorectal excision (TME) of rectomy (205
patients in the TME with laparoscopy group, and 193 patients in the control
group) were included in our study, between October 1997 and December 2013.
Postoperative genital function, local recurrence, and the 5-year survival rate
were analyzed, retrospectively. RESULTS: The rate of erection dysfunction was
lower in the laparoscopic group (60.0%) than in the open group (82.4%, P<0.05);
the rate of ejaculation dysfunction in the laparoscopic group (56.6%) was also
lower than in the open group (82.4%, P<0.05). No significant difference was found
regarding the local recurrence (P=0.87) and the survival rate (P=0.17).
Interestingly, for patients with preoperative obstruction, the survival rate was
lower in the laparoscopy group compared with the control group (P=0.002).
CONCLUSIONS: Laparoscopic surgery should be recommended for mid-RC or low-RC
patients to preserve the postoperative genital function. However, for patients
with preoperative obstruction, laparoscopy surgery was not recommended.
PMID- 26429054
TI - Surgical Residents are Excluded From Robot-assisted Surgery.
AB - PURPOSE: Implementation of a robotic system may influence surgical training. The
aim was to report the charge of the operating surgeon and the bedside assistant
at robot-assisted procedures in urology, gynecology, and colorectal surgery.
MATERIALS AND METHODS: A review of hospital charts from surgical procedures
during a 1-year period from October 2013 to October 2014. All robot-assisted
urologic, gynecologic, and colorectal procedures were identified. Charge of both
operating surgeon in the console and bedside assistant were registered. RESULTS:
A total of 774 robot-assisted procedures were performed. In 10 (1.3%) of these
procedures, a resident attended as bedside assistant and never as operating
surgeon in the console. CONCLUSIONS: Our results demonstrate a severe problem
with surgical education. Robot-assisted surgery is increasingly used; however,
robotic surgical training during residency is almost nonexisting.
PMID- 26429055
TI - An 8-Year Experience With Endoscopic Management of Eroded Gastric Bands.
AB - BACKGROUND/AIMS: We review our 8-year experience with endoscopic removal of
eroded gastric bands. MATERIALS AND METHODS: From 2006 to 2014, 25 patients were
diagnosed with band erosion. Clinical data concerning the endoscopic procedure
were recorded prospectively and reviewed retrospectively. To remove the migrated
band, we used an endoscopic approach with a Gastric Band Cutter (GBC). RESULTS:
The median time interval from the initial gastric band placement to the diagnosis
of band erosion was 41 (18 to 67) months. Upper abdominal pain was the most
common symptom (40%). In 24 of the 25 patients, we used the GBC to remove the
band endoscopically. It was able to cut the band successfully in all cases except
1, where twisting of the cutting wire required conversion from endoscopy to
laparotomy. In 2 cases, the band, after being cut, was locked in the gastric wall
and required laparotomic removal. In 1 patient, we had to perform a surgery for
intragastric penetration of the connecting tube broken close to the band. Our
success rate was 88% in the single session, with no complications. CONCLUSIONS:
Endoscopic removal of a migrated band with the GBC seems to be an effective and
safe method for band erosion.
PMID- 26429056
TI - Laparoscopic Versus Open Resection for Liver Cavernous Hemangioma: A Single
Center of 2-Year Experience.
AB - OBJECTIVE: To evaluate the feasibility and safety of laparoscopic versus open
resection for liver cavernous hemangioma (LCH). MATERIALS AND METHODS: A total of
131 patients suffering from LCH operated in our department between January 2013
and December 2014 were divided into 2 groups: 31 for laparoscopic liver resection
(LR) and 100 for open liver resection (OR). RESULTS: Age, sex, presence or
absence of chronic liver disease, tumor size, tumor location, type of resection,
estimated intraoperative blood loss, operative time, length of postoperative
hospital stay, morbidity, and mortality were equivalent between the 2 groups.
There were no significant differences in estimated intraoperative blood loss
between the LR and OR groups. The operation time of the LR group was longer than
the OR group and the hospitalization expenses less than the OR group. However,
the time of postoperative hospital stay and time of oral intake were shorter in
the LR group than the OR group. The tumor of the LR group was smaller than the OR
group. In liver function, alanine aminotransferase after operation of the LR
group was lower than the OR group, the same as aspartate transaminase after
operation. But there were no significant differences in total bilirubin after
operation. CONCLUSIONS: Laparoscopic resection for LCH is a safe and feasible
procedure as OR.
PMID- 26429057
TI - Case-matched Comparison of Robotic Versus Laparoscopic Colorectal Surgery:
Initial Institutional Experience.
AB - Robotic colorectal surgery is an emerging technique. In this study, we aimed to
compare outcomes of robotic colorectal operations to laparoscopy. Patients
undergoing robotic colorectal surgery between November 2010 and July 2013 were
case matched to laparoscopic counterparts based on diagnosis and operation type.
Perioperative and short-term postoperative outcomes were compared. There were 57
patients who underwent robotic colorectal surgery. American Society of
Anaesthesiologists score was higher in patients who underwent robotic surgery (2
vs. 3, P=0.01). Blood loss (200 vs. 300 mL, P=0.27) and conversion rate to open
surgery (6 vs. 5, P=0.75) were similar between the groups. Operating time was
longer in robotic surgery (172 vs. 267 min, P<0.0001). Time to first bowel
movement (3 vs. 3 d, P=0.38), hospital stay (5 vs. 6 d, P=0.22), and
postoperative complications were comparable between the groups. In the early
learning curve period, robotic colorectal surgery shows similar short-term
outcomes with longer operating time compared with conventional laparoscopy.
PMID- 26429058
TI - Laparoscopic Bile Duct Clearance Without Choledochoscopy.
AB - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) has been proven to
be a safe, efficient, and cost-effective option for the management of common bile
duct (CBD) stones. There are two guiding methods during LCBDE: fluoroscopic or
choledochoscopic. Most surgeons prefer the use of flexible choledochoscopy at
LCBDE, but it is a fragile, delicate, and expensive instrument. The aim of this
work was to report our experience in fluoroscopically guided LCBDE. PATIENTS AND
METHODS: A retrospective review of all patients who underwent LCBDE in the
Mansoura Gastroenterology surgical center between March 2007 and September 2014
was performed. Patients with gallstones and concomitant CBD stones were included.
After the initial assessment, all patients fulfilling the criteria of enrollment
underwent magnetic resonance cholangiopancreatography, and only patients with
magnetic resonance cholangiopancreatography or endoscopic retrograde
cholangiopancreatography evidence of CBD stones were included. Choledochoscopy
was not used in any patient, and we depended on fluoroscopic guidance for CBD
stone retrieval in all LCBDE. RESULTS: A total of 290 patients were assessed for
LCBDE: 76 patients were excluded; 11 patients were not completed laparoscopically
due to negative intraoperative cholangiography (n=7) and conversion to laparotomy
(n=4); the remaining 203 patients were analyzed. LCBDE failed in 16 of the 203
(7.9%) cases, with a success rate of 92.1%. The median operative time was 79
minutes, and the median hospital stay was 2.4 days. Complications were bile
leakage (n=4), mild pancreatitis (n=2), wound infection (n=2), port hernia (n=1),
and internal hemorrhage (n=1). CONCLUSIONS: Compared with published studies using
choledochoscopy at LCBDE, we found comparable results in terms of the
success/failure rate, the morbidity and mortality, the operative time, and the
length of hospital stay. LCBDE under fluoroscopic guidance may be as safe and
efficient as with choledochoscopic guidance.
PMID- 26429059
TI - Retrospective Evaluation of Laparoscopic Versus Open Hartmann's Reversal: A
Single-Institution Experience.
AB - PURPOSE: Restoration of intestinal continuity after Hartmann's procedure has
significant associated morbidity. There has been a trend toward increasing
utilization of laparoscopy in colorectal surgery, with improvements in short-term
outcomes. This study evaluates our experience with laparoscopic Hartmann's
procedure reversal. METHODS: All patients who underwent laparoscopic and open
reversal of Hartmann's procedure between 2007 and 2010 were reviewed.
Demographics, length of stay, postoperative morbidity, and mortality were
compared between the 2 groups. RESULTS: Nineteen patients underwent laparoscopic
Hartmann's reversal and 62 underwent open reversal. There were no statistically
significant differences in demographics, comorbidities, mean operative times,
blood loss, reoperation, and readmission rates between the groups. The
laparoscopic group had a shorter length of hospitalization (5.7 vs. 7.9 d,
P<0.01). CONCLUSIONS: Laparoscopic reversal of Hartmann's pouch is a safe and
feasible alternative to the open reversal technique. Patients who undergo the
laparoscopic technique have a shorter length of hospital stay.
PMID- 26429060
TI - Robot-assisted Laparoscopic Fenestration of Giant Hepatic Cysts.
AB - BACKGROUND: Traditionally, nonparasitic hepatic cysts are marsupialized using
laparotomy. In the last 2 decades, laparoscopic fenestration has become the
preferred treatment for hepatic cysts. However, this technique is limited by 2
dimensional view and the limited mobility of straight laparoscopic instruments.
These limitations may be overcome by the use of a robotic system. We describe
laparoscopic fenestration of giant hepatic cysts using the da Vinci Si robotic
system with the use of the Endowrist One Vessel Sealer. METHODS: Our first
patient is a 32-year-old female with a solitary hepatic cyst. The second patient
is a 51-year-old female with polycystic liver disease. RESULTS: We performed
robot-assisted laparoscopic cyst fenestration with good clinical outcome. No
intraoperative complications occurred and patients recovered rapidly. CONCLUSION:
These data show that the da Vinci Si robotic system is eminently suited for the
laparoscopic fenestration of large hepatic cysts and that this procedure is
associated with rapid recovery.
PMID- 26429061
TI - Single-Incision Laparoscopic Nontraumatic Left Lateral Diaphragmatic Hernia
Repair.
AB - Diaphragmatic hernia is a quite uncommon disease, being congenital or
posttraumatic. Its diagnosis is frequently accidental. Surgical treatment can be
performed through the abdomen as well as through the chest. Laparoscopy and
thoracoscopy offer a surgical benefit because of reduced wall trauma and added
advantages of minimally invasive surgery. Besides the improved cosmetic result,
transumbilical single-incision laparoscopy can add other advantages to minimally
invasive surgery like reduced postoperative pain, shorter hospital stay, and
improved patient's comfort. The authors describe the technique of transumbilical
single-incision laparoscopic suture and mesh reinforcement for a nontraumatic
left lateral diaphragmatic hernia, discovered accidentally in a 45-year-old male.
PMID- 26429063
TI - Transcription coupled nucleotide excision repair in the yeast Saccharomyces
cerevisiae: The ambiguous role of Rad26.
AB - Transcription coupled nucleotide excision repair (TC-NER) is believed to be
triggered by an RNA polymerase stalled at a lesion in the transcribed strand of
actively transcribed genes. Rad26, a DNA-dependent ATPase in the family of
SWI2/SNF2 chromatin remodeling proteins, plays an important role in TC-NER in
Saccharomyces cerevisiae. However, Rad26 is not solely responsible for TC-NER and
Rpb9, a nonessential subunit of RNA polymerase II (RNAP II), is largely
responsible for Rad26-independent TC-NER. The Rad26-dependent and Rpb9-dependent
TC-NER have different efficiencies in genes with different transcription levels
and in different regions of a gene. Rad26 becomes entirely or partially
dispensable for TC-NER in the absence of Rpb4, another nonessential subunit of
RNAP II, or a number of transcription elongation factors (Spt4, Spt5 and the RNAP
II associated factor complex). Rad26 may not be a true transcription-repair
coupling factor that recruits the repair machinery to the damaged sites where
RNAP II stalls. Rather, Rad26 may facilitate TC-NER indirectly, by antagonizing
the action of TC-NER repressors that normally promote transcription elongation.
The underlying mechanism of how Rad26 functions in TC-NER remains to be
elucidated.
PMID- 26429062
TI - Transformation of enriched mammary cell populations with polyomavirus middle T
antigen influences tumor subtype and metastatic potential.
AB - INTRODUCTION: Breast cancer exhibits significant molecular, histological, and
pathological diversity. Factors that impact this heterogeneity are poorly
understood; however, transformation of distinct normal cell populations of the
breast may generate different tumor phenotypes. Our previous study demonstrated
that the polyomavirus middle T antigen (PyMT) oncogene can establish diverse
tumor subtypes when broadly expressed within mouse mammary epithelial cells. In
the present study, we assessed the molecular, histological, and metastatic
outcomes in distinct mammary cell populations transformed with the PyMT gene.
METHODS: Isolated mouse mammary epithelial cells were transduced with a
lentivirus encoding PyMT during an overnight infection and then sorted into
hormone receptor-positive luminal (CD133+), hormone receptor-negative luminal
(CD133-), basal, and stem cell populations using the cell surface markers CD24,
CD49f, and CD133. Each population was subsequently transplanted into syngeneic
cleared mouse mammary fat pads to generate tumors. Tumors were classified by
histology, estrogen receptor status, molecular subtype, and metastatic potential
to investigate whether transformation of different enriched populations affects
tumor phenotype. RESULTS: Although enriched mammary epithelial cell populations
showed no difference in either the ability to form tumors or tumor latency,
differences in prevalence of solid adenocarcinomas and squamous, papillary, and
sebaceous-like tumors were observed. In particular, squamous metaplasia was
observed more frequently in tumors derived from basal and stem cells than in
luminal cells. Interestingly, both molecularly basal and luminal tumors developed
from luminal CD133+, basal, and stem cell populations; however, luminal CD133-
cells gave rise exclusively to molecularly basal tumors. Tumors arising from the
luminal CD133-, basal, and stem cell populations were highly metastatic; however,
luminal CD133+ cells generated tumors that were significantly less metastatic,
possibly due to an inability of these tumor cells to escape the primary tumor
site. CONCLUSIONS: Expression of PyMT within different mammary cell populations
influences tumor histology, molecular subtype, and metastatic potential. The data
demonstrate that luminal CD133+ cells give rise to less metastatic tumors,
luminal CD133- cells preferentially establish basal tumors, and the cell of
origin for squamous metaplasia likely resides in the basal and stem cell
populations.
PMID- 26429065
TI - Nucleosome positioning, nucleotide excision repair and photoreactivation in
Saccharomyces cerevisiae.
AB - The position of nucleosomes on DNA participates in gene regulation and DNA
replication. Nucleosomes can be repressors by limiting access of factors to
regulatory sequences, or activators by facilitating binding of factors to exposed
DNA sequences on the surface of the core histones. The formation of UV induced
DNA lesions, like cyclobutane pyrimidine dimers (CPDs), is modulated by DNA
bending around the core histones. Since CPDs are removed by nucleotide excision
repair (NER) and photolyase repair, it is of paramount importance to understand
how DNA damage and repair are tempered by the position of nucleosomes. In vitro,
nucleosomes inhibit NER and photolyase repair. In vivo, nucleosomes slow down NER
and considerably obstruct photoreactivation of CPDs. However, over-expression of
photolyase allows repair of nucleosomal DNA in a second time scale. It is
proposed that the intrinsic abilities of nucleosomes to move and transiently
unwrap could facilitate damage recognition and repair in nucleosomal DNA.
PMID- 26429064
TI - Chromatin dynamics after DNA damage: The legacy of the access-repair-restore
model.
AB - Eukaryotic genomes are packaged into chromatin, which is the physiological
substrate for all DNA transactions, including DNA damage and repair. Chromatin
organization imposes major constraints on DNA damage repair and thus undergoes
critical rearrangements during the repair process. These rearrangements have been
integrated into the "access-repair-restore" (ARR) model, which provides a
molecular framework for chromatin dynamics in response to DNA damage. Here, we
take a historical perspective on the elaboration of this model and describe the
molecular players involved in damaged chromatin reorganization in human cells. In
particular, we present our current knowledge of chromatin assembly coupled to DNA
damage repair, focusing on the role of histone variants and their dedicated
chaperones. Finally, we discuss the impact of chromatin rearrangements after DNA
damage on chromatin function and epigenome maintenance.
PMID- 26429066
TI - Health and dietary traits of organic food consumers: results from the NutriNet
Sante study.
AB - The dietary and health traits of organic food (OF) consumers have not been
comprehensively described. The aim of this study was to identify factors
associated with OF consumption. Data were collected from 54 283 participants from
the NutriNet-Sante cohort using self-administered web-based questionnaires.
Occasional organic food consumers and regular organic food consumers (ROFC) were
compared with non-organic food consumers (NOFC) using logistical regression
providing an OR and 95 % CI. Adherence to the French food-based guidelines and
interactions between nutritional knowledge and OF consumption in adherence to
dietary guidelines were investigated. Medical history was also assessed in
relation to OF consumption. Compared with NOFC, ROFC were more likely to be
vegetarian (OR 9.93; 95 % CI 7.42, 13.29 in women; OR 13.07; CI 7.00, 24.41 in
men) and were less likely to be aware of nutritional guidelines regarding meat
consumption (OR 0.37; CI 0.34, 0.40 in women; OR 0.41; CI 0.36, 0.47 in men).
Compared with NOFC, ROFC had a lower risk of type II diabetes, hypertension and
CVD; however, this effect was only significant for men. In contrast, organic
consumers were more likely to report food allergies. Consuming OF appeared to
affect the relationship between nutritional knowledge and adequate intake of
meat/poultry/seafood/eggs and starchy food among both sexes. Our study provides
new insights into the diet- and health-related behaviours of OF consumers in a
large sample of participants residing in France. This should be taken into
account in future studies investigating relationships between health and OF
consumption.
PMID- 26429067
TI - Voltage-gated calcium channel blockers deregulate macroautophagy in
cardiomyocytes.
AB - Voltage-gated calcium channel blockers are widely used for the management of
cardiovascular diseases, however little is known about their effects on cardiac
cells in vitro. We challenged neonatal ventricular cardiomyocytes (CMs) with
therapeutic L-type and T-type Ca(2+) channel blockers (nifedipine and mibefradil,
respectively), and measured their effects on cell stress and survival, using
fluorescent microscopy, Q-PCR and Western blot. Both nifedipine and mibefradil
induced a low-level and partially transient up-regulation of three key mediators
of the Unfolded Protein Response (UPR), indicative of endoplasmic (ER) reticulum
stress. Furthermore, nifedipine triggered the activation of macroautophagy, as
evidenced by increased lipidation of microtubule-associated protein 1 light chain
3 (LC3), decreased levels of polyubiquitin-binding protein p62/SQSTM1 and
ubiquitinated protein aggregates, that was followed by cell death. In contrast,
mibefradil inhibited CMs constitutive macroautophagy and did not promote cell
death. The siRNA-mediated gene silencing approach confirmed the pharmacological
findings for T-type channels. We conclude that L-type and T-type Ca(2+) channel
blockers induce ER stress, which is divergently transduced into macroautophagy
induction and inhibition, respectively, with relevance for cell viability. Our
work identifies VGCCs as novel regulators of autophagy in the heart muscle and
provides new insights into the effects of VGCC blockers on CMs homeostasis, that
may underlie both noxious and cardioprotective effects.
PMID- 26429069
TI - Targeting the Hippo Pathway for Anti-cancer Therapies.
AB - The Hippo signaling pathway is critical in regulating tissue homeostasis, organ
size, and tumorigenesis. YAP and TAZ, two major effectors of the Hippo pathway,
function as transcriptional co-activators and promote target gene expression
mainly through interaction with TEAD family transcription factors. As
oncoproteins, YAP and TAZ are frequently activated or highly expressed in various
cancer specimens. Moreover, their activity has been linked to resistance to a few
widely used anti-cancer drugs, and YAP activation contributes to cancer relapse.
Thus, the Hippo pathway, especially YAP/TAZ-TEAD interaction, represents an
attractive target for anti-cancer therapies. Here, we will discuss potential
approaches to inhibit YAP/TAZ activity, and also review currently available small
molecules targeting the Hippo pathway.
PMID- 26429068
TI - Postprandial profiles of CCK after high fat and high carbohydrate meals and the
relationship to satiety in humans.
AB - CONTEXT: CCK is understood to play a major role in appetite regulation.
Difficulties in measuring CCK have limited the potential to assess its profile in
relation to food-induced satiety. Improvements in methodology and progress in
theoretical understanding of satiety/satiation make it timely for this to be
revisited. OBJECTIVE: First, examine how physiologically relevant postprandial
CCK8/33(s) profiles are influenced by fat (HF) or carbohydrate (HCHO) meals.
Second, to examine relationships between postprandial CCK and profiles of satiety
(hunger/fullness) and satiation (meal size). PARTICIPANTS AND DESIGN: Sixteen
overweight/obese adults (11 females/5 males) participated in a randomised
crossover study (46 years, 29.8 kg/m(2)) in a university research centre. Plasma
was collected preprandially and for 180 min postprandially. Simultaneously,
ratings of hunger/fullness were tracked for 180 min before an ad libitum lunch
was provided. RESULTS: CCK8/33(s) levels increased more rapidly and reached a
higher peak following HF compared to HCHO breakfast (F(1,15)=14.737, p<0.01).
Profiles of hunger/fullness did not differ between conditions (F(1,15)=0.505,
p=0.488; F(1,15)=2.277, p=0.152). There was no difference in energy intake from
the ad libitum meal (HF-3958 versus HCHO-3925 kJ; t(14)=0.201, p=0.844).
CCK8/33(s) profiles were not associated with subjective appetite during early and
late phases of satiety; nor was there an association between CCK8/33(s) and meal
size. CONCLUSIONS: These results demonstrate CCK levels were higher after HF meal
compared to HCHO isocaloric meal. There was no association between CCK levels and
intensity of satiety, or with meal size. Under these circumstances, CCK does not
appear to play a unique independent role in satiety/satiation. CCK probably acts
in conjunction with other peptides and the action of the stomach.
PMID- 26429070
TI - 5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP
Ribose)Polymerases (PARPs).
AB - 5-Aminoisoquinolin-1-one (5-AIQ) is a water-soluble inhibitor of the
poly(ADPribose) polymerases (PARPs), lacking isoform-selectivity. Although of
only moderate potency in vitro against PARP-1, it is highly active in many assays
in cells and in models in vivo, indicating excellent uptake. Optimisation of the
several synthetic sequences to 5-AIQ has led to development of a short and
efficient route from 1-chloroisoquinoline. It has been used widely as a
biochemical and pharmacological tool to study the effects of inhibition of the
PARPs. It ameliorates the damage to cells and tissues following reperfusion of
ischaemic tissue, showing significant protective activity in a rodent model of
haemorrhagic shock at the remarkably low dose of 30 ug Kg(-1). Protection is also
seen in models of myocardial infarction, ischaemic kidney and liver disorders,
stroke and organ transplantation. Inhibition of PARP-1 by 5-AIQ causes down
regulation of the activity of NF-kappaB, which then down-regulates the expression
of several gene products. Thus 5-AIQ has anti-inflammatory activity in vivo,
through modulating the expression of cytokines and adhesion molecules. This
indirect inhibition of expression is relevant in the activity of 5-AIQ in models
of arthritis, Parkinson's disease, multiple sclerosis, spinal cord injury,
periodontitis and inflammatory conditions of the lung. Inhibition of expression
of matrix metalloproteinases and other factors gives rise to anti-angiogenic
activity and to remarkable anti-metastatic activity in a mouse model. Thus,
although it has been overtaken by other PARP-inhibiting drugs in the oncological
clinic, 5-AIQ remains a valuable tool to study the roles of PARPs in health and
in diverse diseases.
PMID- 26429071
TI - Trends of reported human cases of brucellosis, Kingdom of Saudi Arabia, 2004
2012.
AB - Human brucellosis is an important zoonotic disease and is especially concerning
in the Kingdom of Saudi Arabia (KSA), where livestock importation is significant.
We analyzed reported human brucellosis disease trends in KSA over time to help
policymakers understand the magnitude of the disease and guide the design of
prevention and control measures. By using data from the national registry from
2004 to 2012, we calculated the cumulative numbers by age group and months.
Trends of incidence rates (IRs) by gender, nationality, and region were also
calculated. We found that there was a greater number of cases (19,130) in the 15
44 years age group than in any other age group. The IRs significantly decreased
from 22.9 in 2004 [95% confidence interval (CI)=22.3, 23.5] to 12.5 in 2012 (95%
CI=12.1, 13). Males had a significantly greater IR than females. Most cases were
reported during spring and summer seasons. The IR of Saudi citizens was
significantly greater than that of non-Saudis, but this difference reduced over
time. The IRs of Al-Qassim, Aseer, and Hail were in the highest 25th percentile.
Young, male Saudi citizens living in highly endemic areas were at greatest risk
of acquiring brucellosis. We recommend vaccinating susceptible animals against
brucellosis and increasing the public's awareness of preventive measures.
PMID- 26429072
TI - Individual and contextual factors associated with community health workers'
performance in Nyanza Province, Kenya: a multilevel analysis.
AB - BACKGROUND: Several African and South Asian countries are currently investing in
new cadres of community health workers (CHWs) as a major part of strategies aimed
at reaching the Millennium Development Goals. However, one review concluded that
community health workers did not consistently provide services likely to have
substantial effects on health and that quality was usually poor. The objective of
this research was to assess the CHWs' performance in Western Kenya and describe
determinants of that performance using a multilevel analysis of the two levels,
individual and supervisor/community. METHODS: This study conducted three surveys
between August and September 2011 in Nyanza Province, Kenya. The participants of
the three surveys were all 1,788 active CHWs, all their supervisors, and 2,560
randomly selected mothers who had children aged 12 to 23 months. CHW performance
was generated by three indicators: reporting rate, health knowledge and household
coverage. Multilevel analysis was performed to describe the determinants of that
performance. RESULTS: The significant factors associated with the CHWs'
performance were their marital status, educational level, the size of their
household, their work experience, personal sanitation practice, number of
supervisions received and the interaction between their supervisors' better
health knowledge and the number of supervisions. CONCLUSION: A high quality of
routine supervisions is one of the key interventions in sustaining a CHW's
performance. In addition, decreasing the dropout rate of CHWs is important both
for sustaining their performance and for avoiding the additional cost of
replacing them. As for the selection criteria of new CHWs, good educational
status, availability of supporters for household chores and good sanitation
practices are all important in selecting CHWs who can maintain their high
performance level.
PMID- 26429074
TI - Simplified sleep restriction impacts objective but not subjective sleep for
people with primary insomnia in primary care.
PMID- 26429073
TI - Mechanisms underlying the antihypertensive effect of Alstonia scholaris.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Alstonia scholaris has a long history of use in
the Ayurveda traditional treatment of various ailments including hypertension. We
have reported the blood pressure lowering activity of the extract of A.
scholaris. The following research aim to delineate the pharmacological mechanism
involve in the antihypertensive action. MATERIALS AND METHOD: Vasorelaxant effect
of the n-butanol fraction of A. scholaris (NBF-ASME) was evaluated on rat aorta
pre-contracted with phenyelphrine (PE, 1 uM). Aortic rings preparation were pre
incubated with various antagonists like 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1
one (ODQ 10 MUM), methylene blue (MB 10 MUM), Nomega-nitro-L-arginine methyl
ester hydrochloride (l-NAME 10 MUM), atropine (10 MUM), indomethacin (1 MUM), ML
9 and various K(+) channel blockers such as glibenclamide (10 MUM) and tetraethyl
ammonium (TEA 10 MUM) for mechanism study. RESULT: The results showed that pre
incubation of aortic rings with the extract (0.5, 1 and 2mg/mL) significantly
inhibit the contractile response of the rings to phenylephrine-induced
contraction (p<0.05-0.001). Removal of endothelium, incubation with L-NAME,
indomethacin, atropine and propranolol did not significantly affect the
relaxation effect of NBF-ASME. Furthermore, the K(+) channel blockers, TEA and
glibenclamide showed no inhibitory effect. However, aortic rings pretreated with
ODQ and ML-9 showed a significant suppression of the relaxation curve of NBF-ASME
(p<0.01-0.001). In Ca(2+)-free solution, NBF-ASME inhibits the release of
intracellular Ca(2+) from the sarcoplasmic reticulum. NBF-ASME also inhibits
calcium chloride (CaCl2)-induced contraction in endothelium-denuded aortic rings.
CONCLUSION: The results from this study suggests that A. scholaris exerts
vasodilation via calcium channels blockade, direct activation of soluble
guanylate cyclase and possibly by also inhibiting the formation of inositol 1, 4,
5-triphosphate.
PMID- 26429076
TI - Moving Toward Global Primordial Prevention in Cardiovascular Disease: The Heart
of the Matter.
PMID- 26429075
TI - The SI! Program for Cardiovascular Health Promotion in Early Childhood: A Cluster
Randomized Trial.
AB - BACKGROUND: The preschool years offer a unique window of opportunity to instill
healthy life-style behaviors and promote cardiovascular health. OBJECTIVES: This
study sought to evaluate the effect of a 3-year multidimensional school-based
intervention to improve life-style-related behaviors. METHODS: We performed a
cluster-randomized controlled intervention trial involving 24 public schools in
Madrid, Spain, that were assigned to either the SI! Program intervention or the
usual curriculum and followed for 3 years. The SI! Program aimed to instill and
develop healthy behaviors in relation to diet, physical activity, and
understanding how the human body and heart work. The primary outcome was change
in the overall knowledge, attitudes, and habits (KAH) score (range 0 to 80). The
intervention's effect on adiposity markers was also evaluated. RESULTS: A total
of 2,062 children from 3 to 5 years of age were randomized. After 3 years of
follow-up, the overall KAH score was 4.9% higher in children in the intervention
group compared with the control group (21.7 vs. 16.4; p < 0.001). A peak effect
was observed at the second year (improvement 7.1% higher than in the control
group; p < 0.001). Physical activity was the main driver of the change in KAH at
all evaluation times. Children in the intervention group for 2 years and 1 year
showed greater improvement than control subjects (5.9%; p < 0.001 and 2.9%; p =
0.002, respectively). After 3 years, the intervention group showed a higher
probability than the control group of reducing the triceps skinfold z-score by at
least 0.1 (hazard ratio: 1.40, 95% confidence interval: 1.04 to 1.89; p = 0.027).
CONCLUSIONS: The SI! Program is an effective strategy for instilling healthy
habits among preschoolers, translating into a beneficial effect on adiposity,
with maximal effect when started at the earliest age and maintained over 3 years.
Wider adoption may have a meaningful effect on cardiovascular health promotion.
(Evaluation of the Program SI! for Preschool Education: A School-Based Randomized
Controlled Trial [Preschool_PSI!]; NCT01579708).
PMID- 26429077
TI - Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in
Relation to Risk of Coronary Heart Disease: A Prospective Cohort Study.
AB - BACKGROUND: The associations between dietary saturated fats and the risk of
coronary heart disease (CHD) remain controversial, but few studies have compared
saturated with unsaturated fats and sources of carbohydrates in relation to CHD
risk. OBJECTIVES: This study sought to investigate associations of saturated fats
compared with unsaturated fats and different sources of carbohydrates in relation
to CHD risk. METHODS: We followed 84,628 women (Nurses' Health Study, 1980 to
2010), and 42,908 men (Health Professionals Follow-up Study, 1986 to 2010) who
were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was
assessed by a semiquantitative food frequency questionnaire every 4 years.
RESULTS: During 24 to 30 years of follow-up, we documented 7,667 incident cases
of CHD. Higher intakes of polyunsaturated fatty acids (PUFAs) and carbohydrates
from whole grains were significantly associated with a lower risk of CHD
comparing the highest with lowest quintile for PUFAs (hazard ratio [HR]: 0.80,
95% confidence interval [CI]: 0.73 to 0.88; p trend <0.0001) and for
carbohydrates from whole grains (HR: 0.90, 95% CI: 0.83 to 0.98; p trend =
0.003). In contrast, carbohydrates from refined starches/added sugars were
positively associated with a risk of CHD (HR: 1.10, 95% CI: 1.00 to 1.21; p trend
= 0.04). Replacing 5% of energy intake from saturated fats with equivalent energy
intake from PUFAs, monounsaturated fatty acids, or carbohydrates from whole
grains was associated with a 25%, 15%, and 9% lower risk of CHD, respectively
(PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated fatty acids,
HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole grains, HR:
0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with
carbohydrates from refined starches/added sugars was not significantly associated
with CHD risk (p > 0.10). CONCLUSIONS: Our findings indicate that unsaturated
fats, especially PUFAs, and/or high-quality carbohydrates can be used to replace
saturated fats to reduce CHD risk.
PMID- 26429078
TI - Pharma Versus Farmer: Food as Heart Medicine.
PMID- 26429080
TI - Analysis of Large Electronic Health Record Databases Supports Blood Pressure
Incident Diabetes Association.
PMID- 26429079
TI - Usual Blood Pressure and Risk of New-Onset Diabetes: Evidence From 4.1 Million
Adults and a Meta-Analysis of Prospective Studies.
AB - BACKGROUND: Reliable quantification of the association between blood pressure
(BP) and risk of type 2 diabetes is lacking. OBJECTIVES: This study sought to
determine the association between usual BP and risk of diabetes, overall and by
participant characteristics. METHODS: A cohort of 4.1 million adults, free of
diabetes and cardiovascular disease, was identified using validated linked
electronic health records. Analyses were complemented by a meta-analysis of
prospective studies that reported relative risks of new-onset diabetes per unit
of systolic blood pressure (SBP). RESULTS: Among the overall cohort, 20 mm Hg
higher SBP and 10 mm Hg higher diastolic BP were associated with a 58% and a 52%
higher risk of new-onset diabetes (hazard ratio: 1.58; 95% confidence interval
[CI]: 1.56 to 1.59; and hazard ratio: 1.52; 95% confidence interval: 1.51 to
1.54), respectively. There was no evidence of a nadir to a baseline BP of 110/70
mm Hg. The strength of the association per 20 mm Hg higher SBP declined with age
and with increasing body mass index. Estimates were similar even after excluding
individuals prescribed antihypertensive or lipid-lowering therapies. Systematic
review identified 30 studies with 285,664 participants and 17,388 incident
diabetes events. The pooled relative risk of diabetes for a 20 mm Hg higher usual
SBP across these studies was 1.77 (1.53 to 2.05). CONCLUSIONS: People with
elevated BP are at increased risk of diabetes. The strength of the association
declined with increasing body mass index and age. Further research should
determine if the observed risk is modifiable.
PMID- 26429081
TI - The Contribution of Tobacco Use to High Health Care Utilization and Medical Costs
in Peripheral Artery Disease: A State-Based Cohort Analysis.
AB - BACKGROUND: Tobacco use is an important preventable cause of peripheral artery
disease (PAD) and a major determinant of adverse clinical outcomes. OBJECTIVES:
This study hypothesized that tobacco use by PAD patients would be associated with
higher health care utilization and associated costs. METHODS: We conducted a
retrospective, cross-sectional study using 2011 claims data from the largest
Minnesota health plan. The total cohort included individuals with 12 months of
continuous enrollment and >= 1 PAD-related claim. Tobacco cessation
pharmacotherapy billing codes were queried in a subgroup with pharmacy benefits.
Outcomes were total costs, annual proportion of members hospitalized, and primary
discharge diagnoses. RESULTS: A PAD cohort of 22,203 was identified, comprising
1,995 (9.0%) tobacco users. A subgroup of 9,027 with pharmacy benefits included
1,158 (12.8%) tobacco users. The total cohort experienced 22,220 admissions. The
pharmacy benefits subgroup experienced 8,152 admissions. Within 1 year, nearly
one-half the PAD tobacco users were hospitalized, 35% higher than nonusers in the
total cohort (p < 0.001) and 30% higher in the subgroup (p < 0.001). In both
cohorts, users were more frequently admitted for peripheral or visceral
atherosclerosis (p < 0.001), acute myocardial infarction (p < 0.001), and
coronary heart disease (p < 0.05). Observed costs in the total cohort were
$64,041 for tobacco users versus $45,918 for nonusers. Costs for tobacco users
also were consistently higher for professional and facility-based care,
persisting after adjustment for age, sex, comorbidities, and insurance type.
CONCLUSIONS: Tobacco use in PAD is associated with substantial increases in PAD
related hospitalizations, coronary heart disease and PAD procedures, and
significantly greater costs. The results suggest that immediate provision of
tobacco cessation programs may be especially cost effective.
PMID- 26429082
TI - Tobacco Use in Peripheral Artery Disease: An Economic Drag.
PMID- 26429083
TI - Psychological Distress Across the Life Course and Cardiometabolic Risk: Findings
From the 1958 British Birth Cohort Study.
AB - BACKGROUND: Research suggests cardiovascular and metabolic diseases are
influenced by psychological distress in adulthood; however, this research is
often limited to adult populations and/or a snapshot measure of distress. Given
emerging recognition that cardiometabolic diseases have childhood origins, an
important question is whether psychological distress earlier in life influences
disease development. OBJECTIVES: This study sought to assess whether life course
patterns of psychological distress assessed from childhood through adulthood
predict biomarkers of cardiometabolic risk in adulthood and whether effects of
sustained distress differ from more limited exposure. METHODS: The sample (n =
6,714) consists of members of the 1958 British Birth Cohort Study who completed
repeated measures of psychological distress and a biomedical survey at age 45
years. Psychological distress profiles over the life course (no distress,
childhood only, adulthood only, or persistent distress) were identified from 6
assessments between ages 7 and 42 years. Cardiometabolic risk was assessed by
combining information on 9 biomarkers of immune, cardiovascular, and metabolic
system function. Covariate adjusted linear regression models were used to assess
associations between distress profiles and cardiometabolic risk. RESULTS:
Compared with those with no distress, cardiometabolic risk was higher among
people with psychological distress in childhood only (beta = 0.11, SE = 0.03, p =
0.0002), in adulthood only (beta = 0.09, SE = 0.03, p = 0.007), and persistent
across the life course (beta = 0.26, SE = 0.04, p < 0.0001). CONCLUSIONS:
Psychological distress at any point in the life course is associated with higher
cardiometabolic risk. This is the first study to suggest that even if distress
appears to remit by adulthood, heightened risk of cardiometabolic disease
remains. Findings suggest early emotional development may be a target for
primordial prevention and for promoting lifelong cardiovascular health.
PMID- 26429084
TI - Psychological Distress and Susceptibility to Cardiovascular Disease Across the
Lifespan: Implications for Future Research and Clinical Practice.
PMID- 26429087
TI - New American College of Cardiology Population Health Agenda to Focus on Primary
Prevention.
PMID- 26429088
TI - Stratified Approach to Health: Integration of Science and Education at the Right
Time for Each Individual.
PMID- 26429086
TI - Fructose and Cardiometabolic Health: What the Evidence From Sugar-Sweetened
Beverages Tells Us.
AB - Recent attention has focused on fructose as having a unique role in the
pathogenesis of cardiometabolic diseases. However, because we rarely consume
fructose in isolation, the major source of fructose in the diet comes from
fructose-containing sugars, sucrose and high fructose corn syrup, in sugar
sweetened beverages and foods. Intake of sugar-sweetened beverages has been
consistently linked to increased risk of obesity, type 2 diabetes, and
cardiovascular disease in various populations. Putative underlying mechanisms
include incomplete compensation for liquid calories, adverse glycemic effects,
and increased hepatic metabolism of fructose leading to de novo lipogenesis,
production of uric acid, and accumulation of visceral and ectopic fat. In this
review we summarize the epidemiological and clinical trial evidence evaluating
added sugars, especially sugar-sweetened beverages, and the risk of obesity,
diabetes, and cardiovascular disease and address potential biological mechanisms
with an emphasis on fructose physiology. We also discuss strategies to reduce
intake of fructose-containing beverages.
PMID- 26429089
TI - Personalized Lifestyle Counseling: An Opportunity for FITs and ECs.
PMID- 26429090
TI - Prevalence of Ideal Cardiovascular Health Among Adults in the United States.
PMID- 26429085
TI - Food Consumption and its Impact on Cardiovascular Disease: Importance of
Solutions Focused on the Globalized Food System: A Report From the Workshop
Convened by the World Heart Federation.
AB - Major scholars in the field, on the basis of a 3-day consensus, created an in
depth review of current knowledge on the role of diet in cardiovascular disease
(CVD), the changing global food system and global dietary patterns, and potential
policy solutions. Evidence from different countries and
age/race/ethnicity/socioeconomic groups suggesting the health effects studies of
foods, macronutrients, and dietary patterns on CVD appear to be far more
consistent though regional knowledge gaps is highlighted. Large gaps in knowledge
about the association of macronutrients to CVD in low- and middle-income
countries particularly linked with dietary patterns are reviewed. Our
understanding of foods and macronutrients in relationship to CVD is broadly
clear; however, major gaps exist both in dietary pattern research and ways to
change diets and food systems. On the basis of the current evidence, the
traditional Mediterranean-type diet, including plant foods and emphasis on plant
protein sources provides a well-tested healthy dietary pattern to reduce CVD.
PMID- 26429091
TI - Adverse Lifestyle Trends Counter Improvements in Cardiovascular Risk Factor
Management in Coronary Patients.
PMID- 26429092
TI - The Unnatural History of Ventricular Septal Defect.
PMID- 26429093
TI - Reply: The Unnatural History of Ventricular Septal Defect.
PMID- 26429094
TI - Reply: Exploring the Role of Transcatheter Aortic Valve Replacement as the
Preferred Treatment for Lower-Risk Patients.
PMID- 26429095
TI - Exploring the Role of Transcatheter Aortic Valve Replacement as the Preferred
Treatment for Lower-Risk Patients.
PMID- 26429096
TI - Meta-Analyses of Dual Antiplatelet Therapy Following Drug-Eluting Stent
Implantation: Do Bleeding and Stent Thrombosis Weigh Similar on Mortality?
PMID- 26429097
TI - Complaint handling in healthcare: expectation gaps between physicians and the
public; results of a survey study.
AB - BACKGROUND: Patients who submit complaints about the healthcare they have
received are often dissatisfied with the response to their complaints. This is
usually attributed to the failure of physicians to respond adequately to what
complainants want, e.g. an apology or an explanation. However, expectations of
complaint handling among the public may colour how they evaluate the way their
own complaint is handled. This descriptive study assesses expectations of
complaint handling in healthcare among the public and physicians. Negative public
expectations and the gap between these expectations and those of physicians may
explain patients' dissatisfaction with complaints procedures. METHODS: We held
two surveys; one among physicians, using a panel of 3366 physicians (response
rate 57 %, containing all kinds of physicians like GP's, medical specialist and
physicians working in a nursing home) and one among the public, using the Dutch
Healthcare Consumer Panel (n = 1422, response rate 68 %). We asked both panels
identical questions about their expectations of how complaints are handled in
healthcare. Differences in expectation scores between the public and the
physicians were tested using non-parametric tests. RESULTS: The public have
negative expectations about how complaints are handled. Physician's expectations
are far more positive, demonstrating large expectation gaps between physicians
and the public. CONCLUSIONS: The large expectation gap between the public and
physicians means that when they meet because of complaint, they are likely to
start off with opposite expectations of the situation. This is no favourable
condition for a positive outcome of a complaints procedure. The negative public
preconceptions about the way their complaint will be handled will prove hard to
change during the process of complaints handling. People tend to see what they
thought would happen, almost inevitably leading to a negative judgement about how
their complaint was handled.
PMID- 26429098
TI - Sparing of the extraocular muscles in mdx mice with absent or reduced utrophin
expression: A life span analysis.
AB - Sparing of the extraocular muscles in muscular dystrophy is controversial. To
address the potential role of utrophin in this sparing, mdx:utrophin(+/-) and
mdx:utrophin(-/-) mice were examined for changes in myofiber size, central
nucleation, and Pax7-positive and MyoD-positive cell density at intervals over
their life span. Known to be spared in the mdx mouse, and contrary to previous
reports, the extraocular muscles from both the mdx:utrophin(+/-) and
mdx:utrophin(-/-) mice were also morphologically spared. In the mdx:utrophin(+/)(
) mice, which have a normal life span compared to the mdx:utrophin(-/-) mice, the
myofibers were larger at 3 and 12 months than the wild type age-matched eye
muscles. While there was a significant increase in central nucleation in the
extraocular muscles from all mdx:utrophin(+/)(-) mice, the levels were still very
low compared to age-matched limb skeletal muscles. Pax7- and MyoD-positive
myogenic precursor cell populations were retained and were similar to age-matched
wild type controls. These results support the hypothesis that utrophin is not
involved in extraocular muscle sparing in these genotypes. In addition, it
appears that these muscles retain the myogenic precursors that would allow them
to maintain their regenerative capacity and normal morphology over a lifetime
even in these more severe models of muscular dystrophy.
PMID- 26429099
TI - A CHRNE frameshift mutation causes congenital myasthenic syndrome in young Jack
Russell Terriers.
AB - Congenital myasthenic syndromes (CMSs) are a group of rare genetic disorders of
the neuromuscular junction resulting in structural or functional causes of
fatigable weakness that usually begins early in life. Mutations in pre-synaptic,
synaptic and post-synaptic proteins have been demonstrated in human cases, with
more than half involving aberrations in nicotinic acetylcholine receptor (AChR)
subunits. CMS was first recognized in dogs in 1974 as an autosomal recessive
trait in Jack Russell Terriers (JRTs). A deficiency of junctional AChRs was
demonstrated. Here we characterize a CMS in 2 contemporary cases of JRT
littermates with classic clinical and electromyographic findings, and
immunochemical confirmation of an approximately 90% reduction in AChR protein
content. Loci encoding the 5 AChR subunits were evaluated using microsatellite
markers, and CHRNB1 and CHRNE were identified as candidate genes. Sequences of
the splice sites and exons of both genes revealed a single base insertion in exon
7 of CHRNE that predicts a frameshift mutation and a premature stop codon. We
further demonstrated this pathogenic mutation in CHRNE in archival tissues from
unrelated JRTs studied 34 years ago.
PMID- 26429101
TI - Safety I and safety II: the past and future of safety management.
PMID- 26429102
TI - Tips and tricks on Demodex density examination by standardized skin surface
biopsy.
PMID- 26429100
TI - Empowering smokers with a web-assisted tobacco intervention to use prescription
smoking cessation medications: a feasibility trial.
AB - BACKGROUND: Varenicline and bupropion, efficacious smoking cessation medications,
have had suboptimal impact due to barriers at the patient, practitioner and
system level. This study explored the feasibility of a web-assisted tobacco
intervention offering free prescription smoking cessation medication by mail if
the smoker visited a physician for authorization. METHODS: Adult Ontarians,
smoking at least 10 cigarettes daily, intending to quit within 30 days, with no
contraindications to bupropion or varenicline were eligible. After an online
assessment, eligible participants received an electronic personalized printable
prescription form for a 12-week course of varenicline or bupropion to bring to a
physician within 3 weeks for authorization, if appropriate. The physician's
office faxed prescriptions to an online pharmacy that couriered medication to the
patient following medication counselling by telephone. Weekly motivational emails
were sent during treatment. Participants were asked to complete follow-up
questionnaires online at 7, 11, 15 and 41 weeks after enrollment. RESULTS: In
total, 1214 individuals submitted an online assessment from April to September
2010 and 73.6 % (95 % confidence interval (CI) = 71.1-76.1 %; n = 893) were
eligible. At least 65.8 % (95 % CI = 62.7-68.9 %; n = 588) of eligible
participants subsequently visited a physician and 58.7 % (95 % CI = 55.5-61.9 %;
n = 524) received medication (50.6 % varenicline [n = 265] and 49.4 % bupropion
[n = 259]). Reasons for not filling a prescription were failure to visit a
physician (80.1 %; 95 % CI = 73.8-86.5 %; n = 121), physician not prescribing the
medication (15.9 %; 95 % CI = 10.1-21.7 %; n = 24) or other reasons (4.0 %; 95 %
CI = 0.9-7.1 %; n = 6). Follow-up response rate was 66.7 % (95 % CI = 63.7-69.8
%; n = 596). Minimal issues were encountered with printing the prescription or
medication delivery. CONCLUSIONS: This study establishes the feasibility of using
the Internet and free medication to enable smokers to engage physicians to treat
this addiction. Implementation of this intervention can be scaled up by
leveraging existing healthcare systems to treat smokers on a population level.
Further evaluation in a randomized controlled trial is necessary. TRIAL
REGISTRATION: ClinicalTrials.gov Identifier NCT01023659.
PMID- 26429103
TI - Repair and regeneration of lumbosacral nerve defects in rats with chitosan
conduits containing bone marrow mesenchymal stem cells.
AB - OBJECTIVES: Despite the great progress in surgical treatment of lumbosacral nerve
injuries caused by high-energy trauma, functional recovery remains poor and
insufficient. Bone marrow mesenchymal stem cells (BMSCs), which express
neurotrophic factors and can also differentiate into nerve cells, have potential
as an effective alternative therapy for lumbosacral nerve defects. The aim of the
present study was to evaluate the functional recovery, nerve regeneration, motor
neuron survival and apoptosis after lumbosacral nerve transection in rats
receiving BMSC transplantation into the chitosan conduit. METHODS: The right L4
L6 nerve roots of rats were transected and bridged with three 1-cm-long chitosan
conduits, which were further injected with the BMSCs (MSC-treated group) or
culture medium (DMEM group). The nerve regeneration and motor function recovery
were assessed by the sciatic functional index (SFI) and analysed
electrophysiologically and morphologically. RESULTS: At 6 and 12 weeks after
surgery, the SFI values in MSC-treated group were significantly higher than those
in DMEM group (P<=0.05). The peak amplitude of CMAP (compound muscle action
potential) and nerve conduction velocity in MSC-treated group were significantly
higher than that in DMEM group (P<=0.01), while the latency of CMAP onset in MSC
treated group was significantly shorter than that in DMEM group (P<=0.01). The
diameter of the myelinated fibres and thickness of the myelin sheath in MSC
treated group were significantly higher than those in DMEM group (P<=0.05). There
was no difference in the number of motor neurons in the anterior horn of the
spinal cord at 6 weeks post-operation (P>0.05), while the number of motor neurons
was significantly greater in MSC-treated group than that in DMEM group at 12
weeks post-operation (P<=0.001). The number of apoptotic cells was also
significantly lower (P<=0.01). CONCLUSIONS: The results of the present study
showed that BMSCs treatment improved lumbosacral nerve regeneration and motor
function. In addition, our data suggested that BMSCs inhibited motor neuron
apoptosis, and improved motor neuron function and survival in the anterior horn
of the spinal cord.
PMID- 26429104
TI - Influence of obesity on surgical outcomes in type III paediatric supracondylar
humeral fractures.
AB - INTRODUCTION: Obesity was associated with poor treatment outcome in paediatric
supracondylar humeral fractures. It is controversial about the association is
related to more severe fractures in obese children or obesity directly affects
treatment. The purpose of this study was to evaluate the influence of obesity on
surgical outcomes after control of fracture severity. PATIENTS AND METHODS: This
is a retrospective comparative study of 107 children treated for type III
supracondylar humeral fractures between January 2009 and December 2013. Children
were classified according to sex-specific body mass index (BMI)-for-age growth
chart into 4 groups: underweight group (n=10); normal-weight group (n=71);
overweight group (n=13); and obese group (n=13). Clinical outcomes were assessed
using the Flynn criteria. Radiographic evaluation included the Baumann angle and
the lateral humerocapitellar angle. Loss of reduction was defined by Skaggs'
criteria. RESULTS: The mean age, sex, and Flynn criteria were comparable among
the four BMI groups. Obese children were more likely to develop a varus change in
the Baumann angle (p=0.017) and loss of reduction in varus (p=0.059)
postoperatively. The risk for pin-related complications was significantly higher
in overweight and obese children (p=0.013). CONCLUSIONS: Obesity was associated
with more postoperative varus deformation and pin-related complications after
surgical fixation for type III supracondylar fracture. These findings underline
the importance of stable fixation and close post-operative monitoring in obese
children.
PMID- 26429106
TI - Remember Ebola?
PMID- 26429105
TI - Predicting in-hospital mortality of traffic victims: A comparison between AIS-and
ICD-9-CM-related injury severity scales when only ICD-9-CM is reported.
AB - BACKGROUND AND AIM: Injury severity scores are important in the context of
developing European and national goals on traffic safety, health-care
benchmarking and improving patient communication. Various severity scores are
available and are mostly based on Abbreviated Injury Scale (AIS) or International
Classification of Diseases (ICD). The aim of this paper is to compare the
predictive value for in-hospital mortality between the various severity scores if
only International Classification of Diseases, 9th revision, Clinical
Modification ICD-9-CM is reported. METHODOLOGY: To estimate severity scores based
on the AIS lexicon, ICD-9-CM codes were converted with ICD Programmes for Injury
Categorization (ICDPIC) and four AIS-based severity scores were derived: Maximum
AIS (MaxAIS), Injury Severity Score (ISS), New Injury Severity Score (NISS) and
Exponential Injury Severity Score (EISS). Based on ICD-9-CM, six severity scores
were calculated. Determined by the number of injuries taken into account and the
means by which survival risk ratios (SRRs) were calculated, four different
approaches were used to calculate the ICD-9-based Injury Severity Scores (ICISS).
The Trauma Mortality Prediction Model (TMPM) was calculated with the ICD-9-CM
based model averaged regression coefficients (MARC) for both the single worst
injury and multiple injuries. Severity scores were compared via model
discrimination and calibration. Model comparisons were performed separately for
the severity scores based on the single worst injury and multiple injuries.
RESULTS: For ICD-9-based scales, estimation of area under the receiver operating
characteristic curve (AUROC) ranges between 0.94 and 0.96, while AIS-based scales
range between 0.72 and 0.76, respectively. The intercept in the calibration plots
is not significantly different from 0 for MaxAIS, ICISS and TMPM. DISCUSSION:
When only ICD-9-CM codes are reported, ICD-9-CM-based severity scores perform
better than severity scores based on the conversion to AIS.
PMID- 26429107
TI - PCMO L01-Setting Specifications for Biological Investigational Medicinal
Products.
AB - This paper provides overall guidance and best practices for the setting of
specifications for clinical biological drug substances and drug products within
the framework of ICH guidelines on pharmaceutical development [Q8(R2) and Q11],
quality risk management (Q9), and quality systems (Q10). A review is provided of
the current regulatory expectations for the specification setting process as part
of a control strategy during product development, pointing to existing challenges
for the investigational new drug/investigational medicinal product dossier
(IND/IMPD) sponsor. A case study illustrates how the investigational medicinal
product specification revision process can be managed within a flexible quality
system, and how specifications can be set and justified for early and late
development stages. LAY ABSTRACT: This paper provides an overview for the setting
of product specifications for investigational medicinal products used in clinical
trials. A case study illustrates how product specifications of investigational
medicinal products can be justified and managed within a modern product quality
system.
PMID- 26429108
TI - Creating a Holistic Extractables and Leachables (E&L) Program for Biotechnology
Products.
AB - The risk mitigation of extractables and leachables presents significant
challenges to regulators and drug manufacturers with respect to the development,
as well as the lifecycle management, of drug products. A holistic program is
proposed, using a science- and risk-based strategy for testing extractables and
leachables from primary containers, drug delivery devices, and single-use systems
for the manufacture of biotechnology products. The strategy adopts the principles
and concepts from ICH Q9 and ICH Q8(R2). The strategy is phase-appropriate,
progressing from extractables testing for material
screening/selection/qualification through leachables testing of final products.
The strategy is designed primarily to ensure patient safety and product quality
of biotechnology products. The holistic program requires robust extraction
studies using model solvents, with careful consideration of solvation effect, pH,
ionic strength, temperature, and product-contact surface and duration. From a
wide variety of process- and product-contact materials, such extraction studies
have identified and quantified over 200 organic extractable compounds. The most
commonly observed compounds were siloxanes, fatty acid amides, and methacrylates.
Toxicology assessments were conducted on these compounds using risk-based
decision analysis. Parenteral permitted daily exposure limits were derived, as
appropriate, for the majority of these compounds. Analysis of the derived
parenteral permitted daily exposure limits helped to establish action thresholds
to target high-risk leachables in drug products on stability until expiry. Action
thresholds serve to trigger quality investigations to determine potential product
impact. The holistic program also evaluates the potential risk for
immunogenicity. This approach for primary drug containers and delivery devices is
also applicable to single-use systems when justified with a historical knowledge
base and understanding of the manufacturing processes of biotechnology products.
LAY ABSTRACT: In the development of a drug product, careful consideration is
given to impurities that may originate from manufacturing equipment, process
components, and packaging materials. The majority of such impurities are common
chemical additives used to improve the physicochemical properties of a wide range
of plastic materials. Suppliers and drug manufacturers conduct studies to extract
chemical additives from the plastic materials in order to screen and predict
those that may leach into a drug product. In this context, the term extractables
refers to a profile of extracted compounds observed in studies under harsh
conditions. In contrast, the term leachables refers to those impurities that
leach from the materials under real-use conditions and may be present in final
drug products. The purpose of this article is to present a holistic approach that
effectively minimizes the risk of leachables to patient safety and product
quality.
PMID- 26429109
TI - Manufacturing of Plasma-Derived Medicinal Products: Qualification Process of
Plasma Suppliers.
AB - Manufacturers of human plasma-derived products ensure, through their
qualification departments, the quality and safety of human plasma-the biological
starting material of the industrial fractionation process. The qualification
department has established written procedures to approve the plasma supplier
(i.e., initial qualification) according to current regulations and to the
manufacturer's plasma specifications. Once the plasma supplier is approved, a
periodical assessment is necessary (i.e., continuous qualification) to guarantee
the level of compliance. In addition, a signed quality agreement between the
plasma supplier and the manufacturer defines the duties and the responsibilities
of both parties. The qualification department implements the following
requirements to ensure the quality of plasma from suppliers: (i) a regular audit
program to confirm the satisfactory initiation of the quality arrangements and
(ii) monitoring of the quality and safety of plasma including critical quality
parameters. For several years, the Grifols Qualification Department has worked
with several plasma suppliers of the European Union (EU) and has performed a
detailed, continuous assessment of the audits, deviations, operational
incidences, epidemiological data, and quality controls. In this article, we will
report data from this Grifols assessment from 2010 through 2013 on plasma
suppliers from four EU countries. In the future, additional data will be
collected and studied to confirm and verify the conclusions and trends observed
in this study.
PMID- 26429111
TI - Introduction to BioPhorum Operations Group (BPOG) Special Section Editorials.
PMID- 26429110
TI - Quality Culture Survey Report.
AB - The Parenteral Drug Association conducted an anonymous global survey of quality
culture in the pharmaceutical industry to determine whether there is a
relationship between certain quality behaviors and certain quality attributes,
and whether these quality attributes could be used as surrogates (or proxy
variables) to assess quality culture. Other studies have shown that an unhealthy
quality culture is a root cause of many quality or compliance issues seen by
sites and organizations. Statistical analysis of survey data suggests that
certain attributes are driving good behaviors, and the demographic data suggests
that this relationship holds irrespective of the geographic location of the site.
Executive survey respondents had a more optimistic view of the current state of
quality culture than survey respondents at large, with cross-functional vision
showing the biggest gap (P-value = 0.07, F-Test). The top five quality attributes
that can serve as surrogates for quality culture were (1) Management
communication that quality is everyone's responsibility, (2) Site has formal
quality improvement objectives and targets, (3) Clear performance criteria for
feedback and coaching, (4) Quality topics included in at least half of all-hands
meetings, and (5) Collecting error prevention metrics. These identified mature
quality attributes are related to management responsibility, and continual
improvement of the pharmaceutical quality system sections of ICH Q10, and
therefore may be amenable to be incorporated in audit programs or in regulatory
inspections. Additional research and discussion is required to build a coherent
approach, which the pharmaceutical industry and regulators can adopt.
PMID- 26429112
TI - Overview of Best Practices for Biopharmaceutical Technology Transfers.
AB - Technology transfer is a key foundational component in product commercialization.
It is more than just the transfer of documents; it relates to all aspects of the
transfer of knowledge and experience to the commercial manufacturing unit to
ensure consistent, safe, and high-quality product. This is the first in a series
of articles from the BioPhorum Operations Group (BPOG) member companies
discussing best practices and benchmarking of biopharmaceutical technology
transfer. In this article, we provide the common terminology developed by BPOG to
accommodate both transferring and receiving organizations. We also review the key
elements of a robust technology transfer business process, including critical
milestones. Finally, we provide a brief overview of the articles in this series.
PMID- 26429113
TI - Strategies for Maximizing Successful Drug Substance Technology Transfer Using
Engineering, Shake-Down, and Wet Test Runs.
AB - The technology transfer of biological products is a complex process requiring
control of multiple unit operations and parameters to ensure product quality and
process performance. To achieve product commercialization, the technology
transfer sending unit must successfully transfer knowledge about both the product
and the process to the receiving unit. A key strategy for maximizing successful
scale-up and transfer efforts is the effective use of engineering and shake-down
runs to confirm operational performance and product quality prior to embarking on
good manufacturing practice runs such as process performance qualification runs.
We consider key factors to consider in making the decision to perform shake-down
or engineering runs. We also present industry benchmarking results of how
engineering runs are used in drug substance technology transfers alongside the
main themes and best practices that have emerged. Our goal is to provide
companies with a framework for ensuring the "right first time" technology
transfers with effective deployment of resources within increasingly aggressive
timeline constraints.
PMID- 26429114
TI - Changing the Performance Paradigm in Pharma/Biotech: Integrating Human
Performance in Global Organizations.
PMID- 26429115
TI - A Computerized Lifestyle Application to Promote Multiple Health Behaviors at the
Workplace: Testing Its Behavioral and Psychological Effects.
AB - BACKGROUND: Preventive health behaviors, such as regular physical activity and
healthy nutrition, are recommended to maintain employability and to facilitate
the health of employees. Theory-based workplace health promotion needs to include
psychological constructs and consider the motivational readiness (so-called
stages of change) of employees. According to the stages, people can be grouped as
nonintenders (not motivated to change and not performing the goal behavior),
intenders (decided to adopt the goal behavior but not started yet), or actors
(performing the goal behavior already). The tailoring to these stages can be done
computer based and should make workplace health promotion more effective.
OBJECTIVE: It was tested whether a parsimonious computer-based health promotion
program implemented at the workplace was effective in terms of lifestyle changes
and psychological outcomes as well as body weight. We hypothesized that the stage
matched intervention would outperform the one-size-fits-all active control
condition (standard care intervention). METHODS: In a randomized controlled
trial, a total of 1269 employees were recruited by a trained research assistant
at their workplace during a routine medical examination. After excluding
noneligible employees, 560 completed Time 1 (T1), and 384 also completed Time 2
(T2), achieving a retention rate of 68.6%. Two fully automated computer-based
treatments were adopted: (1) an active control condition with information about
benefits of exercise and healthy nutrition (n=52), or (2) a stage-matched
multiple-behavior intervention that provided different psychological treatments
to 9 subgroups, addressing stages of change (nonintenders, intenders, and actors
per behavior; n=332). Baseline assessments (T1) on behavior, psychological
constructs, and body weight were repeated after 4 weeks (T2). RESULTS: The stage
matched intervention outperformed the active control condition for lifestyle
changes containing physical activity and nutrition (chi(2) 1=3.5; P=.04, for
N=384) as well as psychological variables (physical activity intention, P=.04;
nutrition intention, P=.03; nutrition planning, P=.02; and general social support
to live healthily, P=.01). When predicting a healthy lifestyle at follow-up,
baseline lifestyle (odds ratio, OR, 2.25, 95% CI 1.73-2.92; P<.01) and the
intervention (OR 1.96, 95% CI 1.00-3.82; P=.05) were found to be significant
predictors. Physical activity planning mediated the effect of the intervention on
the adoption of an overall healthy lifestyle (consisting of activity and
nutrition, R(2) adj=.08; P<.01), indicating that if the stage-matched
intervention increased planning, the adoption of a healthy lifestyle was more
likely. CONCLUSIONS: Matching an intervention to the motivational readiness of
employees can make a health promotion program effective. Employees' motivation,
planning, social support, and lifestyle can be supported by a stage-matched
intervention that focuses on both physical activity and healthy nutrition.
Occupational settings provide a potential to implement parsimonious computer
based health promotion programs and to facilitate multiple behavior change.
PMID- 26429116
TI - Factors Affecting Attendance at an Adapted Cardiac Rehabilitation Exercise
Program for Individuals with Mobility Deficits Poststroke.
AB - OBJECTIVE: The aim of this study was to determine the factors affecting
attendance at an adapted cardiac rehabilitation program for individuals
poststroke. METHODS: A convenience sample of ambulatory patients with hemiparetic
gait rated 20 potential barriers to attendance on a 5-point Likert scale upon
completion of a 6-month program of 24 prescheduled weekly sessions.
Sociodemographic characteristics, depressive symptoms, cardiovascular fitness,
and comorbidities were collected by questionnaire or medical chart. RESULTS:
Sixty-one patients attended 77.3 +/- 12% of the classes. The longer the elapsed
time from stroke, the lower the attendance rate (r = -.34, P = .02). The 4
greatest barriers influencing attendance were severe weather, transportation
problems, health problems, and traveling distance. Health problems included
hospital readmissions (n = 6), influenza/colds (n = 6), diabetes and cardiac
complications (n = 4), and musculoskeletal issues (n = 2). Of the top 4 barriers,
people with lower compared to higher income had greater transportation issues (P
= .004). Greater motor deficits of the stroke-affected leg were associated with
greater barriers related to health issues (r = .7, P = .001). The only
sociodemographic factor associated with a higher total mean barrier score was non
English as the primary language spoken at home (P = .002); this factor was
specifically related to the barriers of cost (P = .007), family responsibilities
(P = .018), and lack of social support (P = .001). No other associations were
observed. CONCLUSION: Barriers to attendance were predominantly related to
logistic/transportation and health issues. People who were more disadvantaged
socioeconomically (language, finances), and physically (stroke-related deficits)
were more affected by these barriers. Strategies to reduce these barriers,
including timely referral to exercise programs, need to be investigated.
PMID- 26429117
TI - Role of sphingosine 1-phosphate receptors, sphingosine kinases and sphingosine in
cancer and inflammation.
AB - Sphingosine kinase (there are two isoforms, SK1 and SK2) catalyses the formation
of sphingosine 1-phosphate (S1P), a bioactive lipid that can be released from
cells to activate a family of G protein-coupled receptors, termed S1P1-5. In
addition, S1P can bind to intracellular target proteins, such as HDAC1/2, to
induce cell responses. There is increasing evidence of a role for S1P receptors
(e.g. S1P4) and SK1 in cancer, where high expression of these proteins in ER
negative breast cancer patient tumours is linked with poor prognosis. Indeed,
evidence will be presented here to demonstrate that S1P4 is functionally linked
with SK1 and the oncogene HER2 (ErbB2) to regulate mitogen-activated protein
kinase pathways and growth of breast cancer cells. Although much emphasis is
placed on SK1 in terms of involvement in oncogenesis, evidence will also be
presented for a role of SK2 in both T-cell and B-cell acute lymphoblastic
leukemia. In patient T-ALL lymphoblasts and T-ALL cell lines, we have
demonstrated that SK2 inhibitors promote T-ALL cell death via autophagy and
induce suppression of c-myc and PI3K/AKT pathways. We will also present evidence
demonstrating that certain SK inhibitors promote oxidative stress and protein
turnover via proteasomal degradative pathways linked with induction of p53-and
p21-induced growth arrest. In addition, the SK1 inhibitor, PF-543 exacerbates
disease progression in an experimental autoimmune encephalomyelitis mouse model
indicating that SK1 functions in an anti-inflammatory manner. Indeed,
sphingosine, which accumulates upon inhibition of SK1 activity, and sphingosine
like compounds promote activation of the inflammasome, which is linked with
multiple sclerosis, to stimulate formation of the pro-inflammatory mediator, IL
1beta. Such compounds could be exploited to produce antagonists that diminish
exaggerated inflammation in disease. The therapeutic potential of modifying the
SK-S1P receptor pathway in cancer and inflammation will therefore, be reviewed.
PMID- 26429118
TI - Obstructive sleep apnea in Prader-Willi syndrome: risks and advantages of
adenotonsillectomy.
AB - Obstructive sleep apnea is a well-known clinical manifestation of Prader-Willi
syndrome. The aim of our study is to evaluate the efficacy of adenotonsillectomy
for the treatment of the disorder as well as the improvement of their post
operative quality of life. Five patients with moderate to severe obstructive
sleep apneas and adenotonsillar hypertrophy of grade III-IV underwent
adenotonsillectomy. Pre- and postoperative apneas and Quality of Life were
assessed respectively with a polysomnography with multi-sleep latency test and
with the pediatric Quality of Life questionnaire, performed before and 6 months
after surgery. A decrease of apnea/hypopnea index values has been detected
between pre- and post-surgery (t=2.64, P=0.005), as well as oxygen desaturation
index values (t=5.51, P=0.005), multi-sleep latency test (t=4.54, P=0.01), and of
the values of pediatric Quality of Life questionnaire. No correlation has been
detected between body mass index and apnea/hypopnea index, oxygen desaturation
index and multi-sleep latency test values pre- and post-adenotonsillectomy. A
correlation has been found between multi-sleep latency test and oxygen
desaturation index values post-surgery (P=0.04). No post-operative complications
were observed. Our data underline the efficacy of surgery in Prader-Willi
patients with adenotonsillar hypertrophy in order to improve their quality of
life.
PMID- 26429119
TI - Laparoscopic herniorrhaphy in children.
AB - The authors report their experience in laparoscopic repair of inguinal hernias in
children. From May 2010 to November 2013, 122 patients with inguinal hernia
underwent laparoscopic herniorrhaphy (92 males and 30 females). Telescope used
was 5 mm, while trocars for the operative instruments were 3 or 2 mm. After
introducing the camera at the umbilical level and trocars in triangulation, a 4-0
nonabsorbable monofilament suture was inserted directly through the abdominal
wall. The internal inguinal ring was then closed by N or double N suture. All
operations were performed in one-day surgery setting. In the case of association
of inguinal and umbilical hernia an original technique was performed for
positioning and fixing the umbilical trocar and for the primary closure of the
abdominal wall defect. The postoperative follow-up consisted of outpatient visits
at 1 week and 1, 3, and 6 months. The mean age of patients was 38.5 months. Of
all patients, 26 were also suffering from umbilical hernia (19 males and 7
females). A total of 160 herniorrhaphies were performed; 84 were unilateral (66
inguinal hernia, 18 inguinal hernia associated with umbilical hernia), 38
bilateral (30 inguinal hernia, 8 inguinal hernia associated with umbilical
hernia). Nine of 122 patients (6 males and 3 females) were operated in emergency
for incarcerated hernia. A pre-operative diagnosis of unilateral inguinal hernia
was performed in 106 cases. Of these patients, laparoscopy revealed a
controlateral open internal inguinal ring in 22 cases (20.7%). The mean operative
time was 29.9+/-15.9 min for the monolateral herniorrhaphies, while in case of
bilateral repair the mean operative time was 41.5+/-10.4 min. The mean operative
time for the repair of unilateral inguinal hernia associated with umbilical
hernia was 30.1+/-7.4 while for the correction of bilateral inguinal hernia
associated with umbilical hernia 39.5+/-10.6 min. There were 3 recurrences
(1.8%): 2 cases in unilateral repair and 1 case a unilateral recurrence in a
bilateral repair. No other complications were seen. Laparoscopic repair of
inguinal hernia in children performed in this experience resulted a safe and
effective procedure.
PMID- 26429120
TI - Ureteral rupture after blunt abdominal trauma in a child with unknown horseshoe
kidney.
AB - More than 90% of renal injuries in children result from blunt abdominal trauma. A
10-year-old female had a blunt abdominal trauma with macro-hematuria. The
computed tomography scan revealed the presence of a horseshoe kidney and a 3rd
grade renal lesion and contrast leakage from the right ureter. The ureteral
rupture was confirmed by cystoscopy and ascendant pyelography and than a double J
stent was implanted. The stent was removed one month later. Non-surgical
management has become the standard of care for both ureteral and renal lesions in
children. Non-surgical treatment is a safe procedure for renal trauma with
ureteral rupture in children.
PMID- 26429121
TI - Mitotic crossover promotes leukemogenesis in children born with TEL-AML1 via the
generation of loss of heterozygosity at 12p.
AB - TEL-AML1 (ETV6-RUNX1) fusion gene which is formed prenatally in 1% of the
newborns, is a common genetic abnormality in childhood Bcell precursor acute
lymphoblastic leukemia. But only one child out of a hundred children born with
this fusion gene develops leukemia (bottleneck phenomenon) later in its life, if
contracts the second mutation. In other words, out of a hundred children born
with TEL-AML1 only one child is at risk for leukemia development, which means
that TEL-AML1 fusion gene is not sufficient for overt leukemia. There is a
stringent requirement for a second genetic abnormality for leukemia development
and this is the real or the ultimate cause of the leukemia bottleneck phenomenon.
In most cases of TEL-AML1+ leukemia, the translocation t(12;21) is complemented
with the loss of the normal TEL gene, not involved in the translocation, on the
contralateral 12p. The loss of the normal TEL gene, i.e. loss of heterozygosity
at 12p, occurs postnatally during the mitotic proliferation of TEL-AML1+ cell in
the mitotic crossing over process. Mitotic crossing over is a very rare event
with a frequency rate of 10-6 in a 10 kb region. The exploration and
identification of the environmental exposure(s) that cause(s) proliferation of
the TELAML1+ cell in which approximately 106 mitoses are generated to cause 12p
loss of heterozygosity, i.e. TEL gene deletion, may contribute to the
introduction of preventive measures for leukemia.
PMID- 26429122
TI - Prevalence of child sexual abuse: a comparison among 4 Italian epidemiological
studies.
AB - Although many epidemiological studies defining child sexual abuse prevalence
rates in many countries of the world are now available, Italy presents a lack of
data regarding this specific issue. Only recently some attempts to define the
epidemiology of this public health problem have been tried. Between 2003 and
2010, the Department of Public Health at University of Milan was in charge of one
of the more important study of this kind in Italy, involving almost 3000 students
aged 18 attending secondary schools in the City of Milan who filled out an
anonymous questionnaire aiming at detecting their previous experiences of sexual
victimization during childhood and adolescence. After this first edition, the
study was replicated among students attending secondary schools in the city of
Varese, in the area of Piedmont and in Basilicata (area of Lauria), using the
same investigational model and questionnaire. This paper presents the main data
collected through four different epidemiological studies using the same
methodology and survey tool. Considering at least one of the five different forms
of child sexual abuse surveyed (being exposed to pornography, being touched on
private parts, being forced to masturbate an older person, being forced to
perform oral sex, or being penetrated), the prevalence rate among our samples
ranges between a minimum of 12.5% (Varese) and a maximum of 34.1% (Lauria). In
Lauria the research reveals a higher prevalence rate of child sexual abuse,
especially among the male population, for all typologies of abuse but being
touched in their private parts. In all other geographical areas and for all
typologies of abuse, there is always a higher prevalence among girls, with the
only exception of abuse such as being exposed to pornographic materials.
PMID- 26429123
TI - A rare case of discrete aortic coarctation in Williams-Beuren syndrome.
Diagnostic and therapeutic considerations.
AB - Williams-Beuren syndrome (WBS) is a genetic disorder caused by elastin gene
deletions, and is characterized by cardiovascular malformations, primarily
including supravalvular aortic stenosis and peripheral pulmonary stenosis. We
report a case of a neonate who developed severe discrete aortic coarctation,
underwent multiple surgical interventions, and was subsequently diagnosed with
WBS. Severe discrete aortic coarctation is a rare event in WBS newborns. An
abnormally thick aortic wall is present in these patients and is the basis of the
failure of the classical approach towards coarctation repair, which consists of
end-to-end anastomosis as first surgical choice. Our case, and a very few similar
previously documented cases, have all demonstrated recoarctation, which only
aortic patch implantation was able to successfully repair. In light of this, we
would also like to underline the importance of early WBS diagnosis. Therefore,
even in mild syndromic phenotype such as low birth weight or facial dysmorphism
that raise the suspicion of a genetic syndrome, it is advisable to perform
fluorescent in situ hybridization analysis rather than merely karyotypic one.
PMID- 26429125
TI - SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): Revised
Publication Guidelines From a Detailed Consensus Process.
PMID- 26429124
TI - Prevalence of overweight/obesity in relation to dietary habits and lifestyle
among 7-17 years old children and adolescents in Lithuania.
AB - BACKGROUND: Until recently increasing prevalence of overweight and obesity among
pediatric population in Europe and worldwide contributes to major well-known
risks for metabolic consequences in later life. The aim of this study was to
determine the prevalence of overweight/obesity among children and adolescents in
Lithuania and assess its association with energy balance related behaviors as
well as familial demographic and socioeconomic factors. METHODS: Cross-sectional
study included 3990 7-17 years old schoolchildren from 40 schools of Kaunas
region, Lithuania. Study participants underwent anthropometric measurements. Body
mass index (BMI) was evaluated according to International Obesity Task Force
(IOTF) criteria for children and adolescents. Children and adolescents and their
parents filled in the questionnaires on parental sociodemographic
characteristics, dietary habits, TV watching time, and family socioeconomic
status. RESULTS: The prevalence of underweight, overweight, and obesity among
boys and girls was 6.9 and 11.7 % (P < 0.05), 12.6 and 12.6 % (P > 0.05), and 4.9
and 3.4 % (P < 0.05), respectively. Obesity was significantly more prevalent in
the 7-9 years old group (6.7 and 4.8 % in boys and girls, respectively, P <
0.05). Lower meals frequency and breakfast skipping were directly associated with
overweight/obesity (P < 0.05); however, physical inactivity was not associated
with higher BMI. Children's overweight/obesity was directly associated with lower
paternal education and unemployment (OR 1.30, P = 0.013 and OR 1.56, P = 0.003,
respectively). CONCLUSIONS: The prevalence of overweight and obesity among 7-17
years old Lithuanian children and adolescents was more prevalent in younger age,
still being one of the lowest across the European countries. Meals frequency,
breakfast skipping, paternal education and unemployment as well as a family
history of arterial hypertension were found to be associated with children's and
adolescents' overweight/obesity.
PMID- 26429126
TI - Factors associated with pain during vascular access intervention therapy.
AB - OBJECTIVE: The objective of this study is to investigate and compare factors
associated with pain during vascular access intervention therapy. SUBJECTS AND
METHODS: Fifty patients provided informed consent to participate in a survey of
pain by questionnaire after receiving dialysis treatment at our hospital.
Balloons for use during the procedure were chosen at random in this prospective
randomized control study. A numeric rating scale (NRS) was used for pain
assessment. RESULTS: A semi-compliant balloon caused significantly worse pain as
compared with the other types of balloons (NRS, 7.67 +/- 1.57 vs. 6.02 +/- 1.89;
p<0.05). There was no correlation between maximum inflation pressure and pain, or
between age and pain, and no difference between diabetic and non-diabetic
patients. A comparison among vascular dilation locations, as well as a comparison
of AVF with AVG also revealed no significant differences. CONCLUSIONS: The reason
for severe pain with use of the semi-compliant balloon as compared with the other
types might have been due to its characteristics during inflation, as increased
diameter leads to an increase in pressure. Mismatching of balloon diameter to
vascular diameter may also increase pain.
PMID- 26429127
TI - An efficacy of intensive vitamin D delivery to neointimal hyperplasia in
recurrent vascular access stenosis.
AB - PURPOSE: Neointimal hyperplasia (NH) causes vascular access (VA) stenosis, which
results in serious under-dialytic morbidity in hemodialysis patients. We sought
to assess whether a vitamin D intervention to NH lesions leads to better VA
patency and examined clinical and in vitro studies. METHODS: A pilot clinical
study of six hemodialysis patients was conducted to elucidate whether 0.5 MUg
calcitriol injection to stenotic lesion after balloon angioplasty (PTA) maintains
better vessel patency until the next follow-up angiography. Localized vitamin D
exposure was utilized by delivering and fixing calcitriol intensively at the
stenotic lesion through a side-hole catheter with balloon clamping. We also
performed vascular smooth muscle cell (VSMC) culture to detect both apoptosis
(cell death detection assay) and cell viability (5-Bromo-2'-deoxy-uridine
incorporation), and explored the efficacy of vitamin D to inhibit VSMC
proliferation. Additionally, immunohistochemistry (IHC) was conducted to examine
vitamin D receptor (VDR) expression at NH lesion, obtained from VA surgery.
RESULTS: Percent patency, the proportion between stenotic and non-stenotic vessel
diameters, increased significantly (p = 0.03) after directly catheter-delivered
0.5 MUg calcitriol administration. In vitro VSMC studies, 0.1 nM calcitriol
significantly (p<0.05) enhanced apoptosis and cell-cycle inhibition for two
different calcitriol exposure times (15 minutes and 24 hours). IHC staining
revealed that VDR-positive hyperplastic cells were observed at NH lesion.
CONCLUSIONS: Intensive vitamin D exposure at NH lesion has an ability to inhibit
further VSMC proliferation, and presumably leads to greater patency rate for
recurrent VA stenosis. Further studies are needed to clarify whether its unique
property is exhibited through VDR-mediated mechanism.
PMID- 26429128
TI - Vascular access for long-term hemodialysis/hemodiafiltration patients.
AB - PURPOSE: We investigated the characteristics of patients who received long-term
hemodialysis/hemodiafiltration (HD/HDF) treatment for over 30 years at our group
of hospitals and type of vascular access (VA) used. SUBJECTS AND METHODS: As of
August 2014, 950 patients were receiving HD/HDF treatment at one of our
hospitals. Of those, we investigated 41 (4.3%) undergoing long-term treatment in
regard to their characteristics and VA type. The items subjected to analysis were
sex, primary illness, age at time of dialysis initiation, present age, duration
(years) of HD/HDF, type of arteriovenous fistula (AVF) and arteriovenous graft
(AVG), history of surgery and AVF persistence rate. RESULTS: The subjects
consisted of 22 men and 19 women, and their mean HD/HDF duration was 33.4 +/- 2.8
years. For primary illness, the majority (n = 31) had chronic glomerulonephritis.
The age at time of dialysis initiation was 31.7 +/- 7.76 years and present age
was 64.5 +/- 7.65 years. They had received 3.8 VA surgeries. For present VA type,
23 patients (56.0%) had an AVF and 13 (31.7%) an AVG, while 4 AVF patients (9.7%)
had a history of AVG use. One patient (2.4%) had a superficialized artery. The
mean HD/HDF duration of the 13 AVG patients was 7 years and the longest was 18
years. AVF persistence rate estimated by the Kaplan-Meier method was 75% at 30
years after dialysis initiation. CONCLUSIONS: The present results suggest that
the ratio of patients with AVG increased with prolonged HD/HDF treatment. AVG has
a higher probability of complications and lower patency as compared to AVF, thus
careful management is needed. On the other hand, AVG contributes more to a good
long prognosis, as it offers efficient dialysis. In cases of vascular
deterioration due to long-term hemodialysis, it is inevitable to change from AVF
to AVG, thus the ratio of AVG patients is expected to increase in cases of long
term HD/HDF.
PMID- 26429129
TI - Clinical significance of perineural invasion in stages II and III colorectal
cancer.
AB - PURPOSE: This study aimed to determine the prognostic value of perineural
invasion (PNI) in patients with colorectal cancer (CRC), particularly patients
with TNM stage II and stage III. METHODS: A total of 159 CRC patients who had
undergone radical resection were retrospectively analyzed. Histopathological
evaluation of tissue samples was conducted on hematoxylin and eosin-stained
sections. PNI was considered positive when cancer cells were observed inside the
nerve sheath, or when at least 33% of the nerve periphery was surrounded by
cancer cells. A 3-tier grading system (PNI0, PNI1, PNI2) based on the depth of
PNI was used to assess the localization of PNI in the bowel. PNI and other
prognostic factors were evaluated by survival analysis. RESULTS: PNI status in
CRC significantly affected postoperative overall survival (P<0.001). The five
year survival rates for PNI-negative and PNI-positive patients were 77% and 32%,
respectively. PNI was closely correlated with tumor gross type, tumor grade,
depth of invasion, lymph node metastasis, clinical stage, vessel invasion, tumor
budding grade, and tumor growth pattern. Multivariate analysis revealed that PNI
was an independent prognostic factor (HR=2.223, P=0.003). The survival of PNI
positive patients was significantly poorer than that of PNI-negative patients in
stages II and III (P=0.003 and P=0.008, respectively). The overall survival of
colorectal patients was in the descending order of PNI-negative at stage II, PNI
positive at stage II/PNI-negative at stage III, and PNI-positive at stage III
(P<0.001). When the PNI status and T stage were considered together, overall
survival curves of the PNI2 patients were significantly worse than those of PNI1
patients in pT4 stage (P=0.019). CONCLUSIONS: PNI is a poor independent
prognostic factor for CRC. It could complement classic TNM staging classification
in stratifying CRC patients in stages II and III. Assessment of the site-specific
distribution of PNI may further enhance the impact of PNI contribution to the
prognosis of CRC.
PMID- 26429130
TI - Pharmacological and morphological characteristics of the muscular system of the
giant liver fluke (Fascioloides magna - Bassi 1875).
AB - Motility is required for feeding, reproduction and maintenance of the fluke in
the host's liver. According to that, the neuromuscular system can be an
attractive drugable target for chemotherapy. Musculature of the Fascioloides
magna is organized into three layers, an outer circular layer, beneath this layer
the longitudinal layer, and third, the oblique, or diagonal layer underlies the
longitudinal layer. In our study, the administration of atropine or caffeine did
not cause classic muscle contractions of F. magna muscle strips. However, the
Electrical Field Stimulation (EFS) induced stable and repeatable contractions,
which enabled us to examine their sensitivity to the various substances.
Acetylcholine (ACh) (300 MUM and 1 mM), caused only a slight relaxation, without
affecting the amplitude of spontaneous contractions or the amplitude of
contractions induced by EFS. Contrary to that, atropine (100 MUM) caused a
significant increase in the basal tone and an increase of EFS-induced
contractions. If acetylcholine is an inhibitory neurotransmitter in trematodes,
the described effects of atropine are achieved by the blockade of inhibitory
neurotransmission. On the other hand, with respect to the process of excitation
contraction coupling, the plant alkaloid ryanodine (30 MUM) significantly reduced
the basal tone, as well as EFS-induced contractions of F. magna muscle strips.
Ryanodine inhibited the potentiating effect of atropine on the basal tone and
contractions caused by EFS, which indicates that the contractile effect of
atropine is dependent on Ca(++) release from intracellular stores. Caffeine (500
MUM) caused relaxation of fluke muscle strips and at the same time significantly
enhanced the EFS-induced contractions. Both effects of caffeine can be explained
by entry of extracellular Ca(++) into muscle cells. The muscle contractility of
F. magna depends both on the entry of extracellular calcium, and calcium release
from intracellular stores, which are under the control of RyRs. Our results also
suggest that antitrematodal drugs could potentially be developed from substances
with selective anti-cholinergic activity.
PMID- 26429131
TI - Allele repeat structure and designation update for the Y-STR loci DYF399S1,
DYS526b and DYS626.
PMID- 26429132
TI - Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential
of a cultured Himalayan lichen Cetrelia olivetorum.
AB - CONTEXT: Lichens are source of natural bioactive compounds which are
traditionally used to cure a variety of ailments. OBJECTIVE: The objective of
this study is to assess free radical scavenging, prolyl endopeptidase inhibitory
(PEPI), and antimicrobial potential of a high altitude lichen species Cetrelia
olivetorum (Nyl.) W. L. Culb. & C. F. Culb (Parmeliaceae). MATERIALS AND METHODS:
Lichen C. olivetorum has been cultured in vitro, and optimized culture conditions
were implemented in bioreactor to obtain high quantity of biomass for the study
of radical scavenging, PEPI, and antimicrobial activities. Radical scavenging
activity of methanol extract of Cetrelia olivetorum (MECO) was tested at 100
ug/mL, PEPI activity at 25 and 50 ug/mL, and antimicrobial activity at 5, 25, 50,
and 100 ug/mL conc. All the biological activities of natural thallus extract and
its derived culture extract were evaluated spectrophotometrically. RESULTS:
Murashige and Skoog medium supplemented with 3% glucose and 100 ppb indole-3
butyric acid (IBA) supported biomass growth at flask level and yielded 5.095 g
biomass in bioreactor. MECO of both the cultured and the natural lichen exhibited
half inhibiting concentration (IC50) for radical scavenging activities in the
range of 50-60 ug/mL, whereas the IC50 value of standard antioxidants was found
to be in the range of 12-29 ug/mL. The IC50 value of lichen extract for PEPI
activity was 144-288 ug/mL, whereas the IC50 value of standard prolyl
endopeptidase inhibitor, Z-pro-prolinal, was 57.73 ug/mL. As far as the
antimicrobial activity of MECO is concerned, minimum inhibitory concentration
(MIC) value of lichen extracts against tested microorganisms was obtained in the
range of 50-104 ug/mL and found to be more effective than commercially available
standard erythromycin. DISCUSSION: Murashige and Skoog medium containing IBA was
found to be suitable for maximum biomass production of C. olivetorum under
bioreactor conditions. The cultured lichen biomass extract also showed
antioxidant, PEPI, and antimicrobial potential. CONCLUSION: The present study
indicates therapeutic potential of Himalayan lichen C. olivetorum against
neurodegenerative diseases owing to its radical scavenging, PEPI, and
antimicrobial activities. Further, the result encourages its commercial
exploitation through mass culture for production of its bioactive components and
their use in pharmaceutical and nutraceutical industries.
PMID- 26429133
TI - Re: Trans-cranial motor evoked potential detection of femoral nerve injury in
trans-psoas lateral lumbar interbody fusion by Justin W. Silverstein.
PMID- 26429134
TI - Accuracy and precision of transcardiopulmonary thermodilution in patients with
cardiogenic shock.
AB - Hemodynamic monitoring plays a crucial role in the supportive treatment of
critically ill patients. In this setting, the use of the pulmonary artery
catheter (PAC) is a standard procedure. In this study we prospectively compare
the accuracy and precision of pulmonary thermodilution (PTD) by PAC and
transcardiopulmonary thermodilution (TC-PTD) in patients with cardiogenic shock
following an acute cardiac event. In this prospective study 77 hemodynamic
measurements were taken in 11 patients presenting cardiogenic shock (CS) treated
at the medical intensive care unit of our university hospital. Hemodynamic
parameters were measured simultaneously by PTD and by TC-PTD. Both techniques
assessed showed a strong correlation in the obtained hemodynamic parameters. The
mean bias of cardiac index between measured by PTD (CIpa) and by TC-PTD (CIpi)
was 0.04 +/- 0.35 L/min/m2. During intra-aortic balloon pump (IABP)
counterpulsation and therapeutic hypothermia (TH) in post-resuscitation care,
mean bias between CIpa and CIpi was 0.04 +/- 0.36 and 0.04 +/- 0.34 L/min/m2,
respectively. Similarly, patients presenting mitral or tricuspid regurgitation
showed interchangeable parameters. Preload parameters obtained by TC-PTD showed
significant differences in patients with left ventricular ejection fraction
(LVEF) <35 %, compared to patients with LVEF >=35 %. In contrast, pulmonary
arterial occlusion pressure showed no significant difference. Hemodynamic
measurements by PTD and TC-PTD are interchangeable during therapy of CS,
including patients IABP, TH, mitral or tricuspid regurgitation. Preload
parameters measured by TC-PTD seem to be more accurate in these patients than
pressure parameters of PTD to gather the acute hemodynamic situation.
PMID- 26429135
TI - Comparison of cardiac output measures by transpulmonary thermodilution, pulse
contour analysis, and pulmonary artery thermodilution during off-pump coronary
artery bypass surgery: a subgroup analysis of the cardiovascular anaesthesia
registry at a single tertiary centre.
AB - Cardiac output measurement has a long history in haemodynamic management and many
devices are now available with varying levels of accuracy. The purpose of the
study was to compare the agreement and trending abilities of cardiac output, as
measured by transpulmonary thermodilution and calibrated pulse contour analysis,
using the VolumeViewTM system, continuous thermodilution via a pulmonary artery
catheter, and uncalibrated pulse contour analysis, using FloTracTM with pulmonary
artery bolus thermodilution. Twenty patients undergoing off-pump coronary artery
bypass surgery using a pulmonary artery catheter and the VolumeViewTM and
FloTracTM systems were included in this subgroup analysis of the cardiovascular
anaesthesia registry at a single tertiary centre. During surgery, cardiac output
was assessed after the induction of anaesthesia, after sternotomy, during the
harvesting of grafts, during revascularization of the anterior and
posterior/lateral wall, after protamine infusion, and after sternal fixation. In
total, 145 sets of measurements were evaluated using Bland-Altman with % error
calculation, correlation, concordance, and polar plot analyses. The percentage
error (bias, limits of agreement) was 12.6 % (-0.12, -0.64 to 0.41 L/min), 26.7 %
(-0.38, -1.50 to 0.74 L/min), 29.3 % (-0.08, -1.32 to 1.15 L/min), and 33.8 % (
0.05, -1.47 to 1.37 L/min) for transpulmonary thermodilution, pulmonary artery
continuous thermodilution, calibrated, and uncalibrated pulse contour analysis,
respectively, compared with pulmonary artery bolus thermodilution. All pairs of
measurements showed significant correlations (p < 0.001), whereas only
transpulmonary thermodilution revealed trending ability (concordance rate of 95.1
%, angular bias of 1.33 degrees , and radial limits of agreement of 28.71 degrees
) compared with pulmonary artery bolus thermodilution. Transpulmonary
thermodilution using the VolumeViewTM system provides reliable data on cardiac
output measurement and tracking the changes thereof when compared with pulmonary
artery bolus thermodilution in patients with preserved cardiac function during
off-pump coronary artery bypass surgery. Trial registration NCT01713192
(ClinicalTrials.gov).
PMID- 26429136
TI - The washout effect during laundry on benzothiazole, benzotriazole, quinoline, and
their derivatives in clothing textiles.
AB - In two previous papers, the authors have shown that benzothiazole, benzotriazole,
quinoline, and several of their derivatives are widespread in clothing textile
articles. A number of these compounds exhibit allergenic and irritating
properties and, due to their octanol-water partition coefficient, are prone to be
absorbed by the skin. Moreover, they are slightly soluble in water, which could
make washing of clothes a route of emission into the environment. In the present
study, the washout effect of benzothiazole, benzotriazole, quinoline, and some of
their derivatives has been investigated. Twenty-seven textile samples were
analyzed before, as well as after five and ten times of washing. The most
abundant analyte was found to be benzothiazole, which was detected in 85 % of the
samples with an average concentration of 0.53 MUg/g (median 0.44 MUg/g), followed
by quinoline, detected in 81 % of the samples with an average concentration of
2.42 MUg/g (median 0.21 MUg/g). The average decrease in concentration for
benzothiazoles was 50 % after ten times washing, while it was around 20 % for
quinolines. The average emission to household wastewater of benzothiazoles and
quinolines during one washing (5 kg of clothes made from polyester materials) was
calculated to 0.5 and 0.24 g, respectively. These results strongly indicate that
laundering of clothing textiles can be an important source of release of these
compounds to household wastewater and in the end to aquatic environments. It also
demonstrates a potential source of human exposure to these chemicals since
considerable amounts of the compounds remain in the clothes even after ten times
of washing.
PMID- 26429137
TI - Identifying spatial and seasonal patterns of river water quality in a semiarid
irrigated agricultural Mediterranean basin.
AB - A detailed understanding of the study area is essential to achieve key
information and optimize the monitoring, analysis, and evaluation of water
quality of natural ecosystems that have been highly transformed into agricultural
areas. Using classification techniques like the hierarchical cluster analysis
(CA) and partial triadic analysis (PTA), we assessed the sources of water
pollution and the seasonal influence of human activities in water composition in
a river basin from northeastern Spain. The results suggested that a strong
connection existed between water quality and the seasonality of the human
activities. The CA showed the spatial relationship between water chemistry and
the adjacent land uses. The PTA associated the analyzed variables to their
pollutant source. Electrical conductivity (EC), Cl(-), SO4(2-)-S, Na(+), and
Mg(2+) ions were related with agricultural sources, whereas NH4(+)-N, PT, and
PO4(3-)-P were linked with urban polluted sites. Concentration of NO3(-)-N was
associated with urban land use. Differences in water composition according to the
irrigation intensity were also found during the irrigation season. The
statistical tools used in this work, especially the PTA, allowed us to jointly
analyze the spatial and seasonal components of water pollutant trends. We
obtained a more comprehensive knowledge of water quality patterns in the study
area, which will be essential when taking measures to minimize the effects of
water pollution.
PMID- 26429138
TI - Microbial community characteristics during simultaneous nitrification
denitrification process: effect of COD/TP ratio.
AB - To evaluate the impact of chemical oxygen demand (COD)/total phosphorus (TP)
ratio on microbial community characteristics during low-oxygen simultaneous
nitrification and denitrification process, three anaerobic-aeration (low-oxygen)
sequencing batch reactors, namely R1, R2, and R3, were performed under three
different COD/TP ratios of 91.6, 40.8, and 27.6. The community structures of each
reactor were analyzed via molecular biological technique. The results showed that
the composition of ammonia-oxidizing bacteria (AOB) was affected, indicated by
Shannon indexes of the samples from R1, R2, and R3. Nitrosomonas was identified
to be the dominant AOB in all SBRs. Moreover, the copy numbers of nitrifiers were
more than those of denitrifiers, and the phosphorus-accumulating organisms to
glycogen-accumulating organisms ratio increased with the decrease of COD/TP
ratio.
PMID- 26429139
TI - Proteomics analysis of liver tissues from C57BL/6J mice receiving low-dose 137Cs
radiation.
AB - Differentially expressed proteins in liver tissues of C57BL/6J mice receiving low
dose (137)Cs radiation were examined by proteomics analysis. Compared with the
control group, 80 proteins were differentially expressed in the irradiated group.
Among the 40 randomly selected proteins used for peptide mass fingerprinting
analysis and bioinformatics, 24 were meaningful. These proteins were related to
antioxidant defense, amino acid metabolism, detoxification, anti-tumor
development, amino acid transport, anti-peroxidation, and composition of
respiratory chain. Western blot analysis showed that catalase (CAT), glycine N
methyltransferase (GNMT), and glutathione S-transferase P1 (GSTP1) were up
regulated in the irradiated group; these results were in agreement with qPCR
results. These results show that CAT, GNMT, and GSTP1 may be related to stress
response induced by low-dose irradiation in mice liver. The underlying mechanism
however requires further investigation.
PMID- 26429141
TI - Stormwater infiltration and surface runoff pollution reduction performance of
permeable pavement layers.
AB - In this paper, the laboratory-scale permeable pavement layers, including a
surface permeable brick layer, coarse sand bedding layers (thicknesses = 2, 3.5,
and 5 cm), and single-graded gravel sub-base layers (thicknesses = 15, 20, 25,
and 30 cm), were built to evaluate stormwater infiltration and surface runoff
pollution reduction performance. And, the infiltration rate (I) and
concentrations of suspended solids (SS), total phosphorus (TP), chemical oxygen
demand (COD), ammonia nitrogen, and total nitrogen (TN) were measured under the
simulated rainfall intensity of 72.4 mm/h over duration of 60 min. The results
indicate that the thickness factor primarily influences the infiltration rate and
pollutant removal rate. The highest steady infiltration rate was for surface
brick layer 51.0 mm/h, for 5-cm sand bedding layer 32.3 mm/h, and for 30-cm
gravel sub-base layer 42.3 mm/h, respectively. The SS average removal rate was
relative higher (79.8 ~ 98.6 %) for all layers due to the interception and
filtration. The average removal rates of TP and COD were for surface layer 71.2
and 24.1 %, for 5-cm bedding layer 54.8 and 9.0 %, and for 20-cm sub-base layer
72.2 and 26.1 %. Ammonia nitrogen and TN cannot steadily be removed by layers
according to the experiment results. The optimal thickness of bedding sands was 5
cm, and that of sub-base gravels was 20 ~ 30 cm.
PMID- 26429140
TI - Contaminant transport in the sub-surface soil of an uncontrolled landfill site in
China: site investigation and two-dimensional numerical analysis.
AB - A field investigation of contaminant transport beneath and around an uncontrolled
landfill site in Huainan in China is presented in this paper. The research aimed
at studying the migration of some chemicals present in the landfill leachate into
the surrounding clayey soils after 17 years of landfill operation. The
concentrations of chloride and sodium ions in the pore water of soil samples
collected at depths up to 15 m were obtained through an extensive site
investigation. The contents of organic matter in the soil samples were also
determined. A two-dimensional numerical study of the reactive transport of sodium
and chloride ion in the soil strata beneath and outside the landfill is also
presented. The numerical modelling approach adopted is based on finite
element/finite difference techniques. The domain size of approximately 300 * 30 m
has been analysed and major chemical transport parameters/mechanisms are
established via a series of calibration exercises. Numerical simulations were
then performed to predict the long-term behaviour of the landfill in relation to
the chemicals studied. The lateral migration distance of the chloride ions was
more than 40 m which indicates that the advection and mechanical dispersion are
the dominant mechanism controlling the contaminant transport at this site. The
results obtained from the analysis of chloride and sodium migration also
indicated a non-uniform advective flow regime of ions with depth, which were
localised in the first few metres of the soil beneath the disposal site. The
results of long-term simulations of contaminant transport indicated that the
concentrations of ions can be 10 to 30 times larger than that related to the
allowable limit of concentration values. The results of this study may be of
application and interest in the assessment of potential groundwater and soil
contamination at this site with a late Pleistocene clayey soil. The obtained
transport properties of the soils and the contaminant transport mechanisms can
also be used for the design of engineered barriers for the control of the long
term pollution of the site.
PMID- 26429142
TI - Biomechanical Changes After Thoracic Endovascular Aortic Repair in Type B
Dissection: A Systematic Review.
AB - Thoracic endovascular aortic repair (TEVAR) has evolved into an established
treatment option for type B aortic dissection (TBAD) since it was first
introduced 2 decades ago. Morbidity and mortality have decreased due to the
minimally invasive character of TEVAR, with adequate stabilization of the
dissection, restoration of true lumen perfusion, and subsequent positive aortic
remodeling. However, several studies have reported severe setbacks of this
technique. Indeed, little is known about the biomechanical behavior of implanted
thoracic stent-grafts and the impact on the vascular system. This study sought to
systematically review the performance and behavior of implanted thoracic stent
grafts and related biomechanical aortic changes in TBAD patients in order to
update current knowledge and future perspectives.
PMID- 26429144
TI - Isolation, Characterization, and Antiproliferative Activities of Eudesmanolide
Derivatives from the Flowers of Inula japonica.
AB - Inula japonica belongs to the family Asteraceae, and its flowers have been used
as dietary supplements and health tea in China. The study aimed to identify the
bioactive components with the antiproliferative property. Ten 1,10-seco
eudesmanolide derivatives, including four new compounds (1-4), were isolated from
the flowers of I. japonica. Their structures were established on the basis of the
interpretation of spectroscopic data and electronic circular dichroism (ECD)
calculations. All of these isolates were evaluated for their antiproliferative
activities against MCF-7 and MDA-MB-231 human breast cancer cells. Compound 4
possessed the most potent effects, with the IC50 values of 0.20 +/- 0.04 and 6.22
+/- 1.30 MUM against MCF-7 and MDA-MB-231 cells, respectively. The present
investigation indicated that eudesmanolide derivatives from the flowers of I.
japonica, especially compound 4, might be used as potential antitumor
chemotherapy agent candidates.
PMID- 26429145
TI - Early changes in morphology, bone mineral density and matrix composition of
vertebrae lead to disc degeneration in aged collagen IX -/- mice.
AB - Collagen IX (Col IX) is an important component of the cartilage
extracellularmatrix and has been associated with degenerative cartilage disorders
and chondrodysplasias in humans. Further, polymorphisms in Col IX are known risk
factors for the development of early intervertebral disc (IVD) degeneration. To
understand the role of Col IX in the pathogenesis of IVD disorders, the spine of
newborn and older Col IX deficient mice was systematically analyzed and compared
to C57BL/6N controls. Morphology and bone parameters of the spine from newborn, 6
and 10 months old animals were investigated using MUCT measurements. Histological
staining was used to evaluate tissue structure and degree of degeneration.
Localization and expression of extracellularmatrix proteins was analyzed in depth
by immunofluorescence staining, immunoblotting, RT-PCR and in situ hybridization.
High resolution imaging and stiffness measurements were performed by atomic force
microscopy (AFM). Vertebral bodies of newborn Col IX-deficient mice were smaller
and showed an increased mineral density compared to wild type animals. At birth,
lack of Col IX led to a disrupted cellular organization in the cartilaginous
endplate and a smaller nucleus pulposus of the IVD.Expression levels and
localization of other extracellularmatrix proteins were strongly altered
accompanied by a softening of cartilaginous tissues. In older animals, absence of
Col IX caused earlier and more pronounced disc degeneration with annular
fissures. The absence of Col IX induces early developmental, structural and
biomechanical alterations in both vertebral body and intervertebral disc which
eventually cause severe degenerative changes in the aging spine.
PMID- 26429146
TI - One-Step Protein Conjugation to Upconversion Nanoparticles.
AB - The emerging upconversion nanoparticles offer a fascinating library of
ultrasensitive luminescent probes for a range of biotechnology applications from
biomarker discovery to single molecule tracking, early disease diagnosis, deep
tissue imaging, and drug delivery and therapies. The effective bioconjugation of
inorganic nanoparticles to the molecule-specific proteins, free of agglomeration,
nonspecific binding, or biomolecule deactivation, is crucial for molecular
recognition of target molecules or cells. The current available protocols require
multiple steps which can lead to low probe stability, specificity, and
reproducibility. Here we report a simple and rapid protein bioconjugation method
based on a one-step ligand exchange using the DNAs as the linker. Our method
benefits from the robust DNA-protein conjugates as well as from multiple ions
binding capability. Protein can be preconjugated via an amino group at the 3' end
of a synthetic DNA molecule, so that the 5' end phosphoric acid group and
multiple phosphate oxygen atoms in the phosphodiester bonds are exposed to
replace the oleic acid ligands on the surface of upconversion nanoparticles due
to their stronger chelating capability to lanthanides. We demonstrated that our
method can efficiently pull out the upconversion nanoparticles from organic
solvent into an aqueous phase. The upconversion nanoparticles then become
hydrophilic, stable, and specific biomolecules recognition. This allows us to
successfully functionalize the upconversion nanoparticles with horseradish
peroxidise (HRP) for catalytic colorimetric assay and for streptavidin (SA)
biotin immunoassays.
PMID- 26429147
TI - Effect of hopelessness on the links between psychiatric symptoms and suicidality
in a vulnerable population at risk of suicide.
AB - The aim of this study was to examine the impact of two risk factors working
together on a measure of suicide probability in a highly vulnerable group who
were male prisoners identified as being at risk of self harm. The first risk
factor was psychiatric symptoms, including general psychiatric symptoms and
symptoms of personality disorder. The second risk factor was psychological
precursors of suicidal thoughts and behaviours which were defeat, entrapment, and
hopelessness. Sixty-five male prisoners from a high secure prison in NW England,
UK, were recruited, all of whom were considered at risk of suicide by prison
staff. General psychiatric symptoms and symptoms of personality disorders
predicted the probability of suicide. Hopelessness amplified the strength of the
positive relationship between general psychiatric symptoms and suicide
probability. These amplification effects acted most strongly on suicidal ideation
as opposed to negative self evaluations or hostility. In contrast, defeat,
entrapment and hopelessness did not affect the relationship between personality
disorders and suicide probability. Clinical assessments of highly vulnerable
individuals, as exemplified by prisoners, should include measures of a range of
general psychiatric symptoms, together with measures of psychological components,
in particular perceptions of hopelessness.
PMID- 26429148
TI - Relationships between cyberchondria and obsessive-compulsive symptom dimensions.
AB - Researchers have recently begun to investigate a vicious cycle of escalating
physical health concerns and online medical information seeking coined
"cyberchondria". Research has shown that cyberchondria is strongly associated
with health anxiety (HA), but there is a dearth of work investigating the
potential relationships between cyberchondria and other anxiety-related
pathologies. One such condition is obsessive-compulsive disorder (OCD), which
could theoretically be related to cyberchondria given the physical health
relevant focus of certain types of OC symptoms. The current study sought to
investigate the potential relationship between cyberchondria OCD across OC
symptom dimensions. Community participants (N=468) were recruited via online
crowdsourcing to complete a battery of self-report questionnaires including
cyberchondria and OC measures. Structural equation modeling revealed significant
unique associations between both contamination/washing and responsibility for
harm/checking symptoms, and cyberchondria, such that greater cyberchondria was
associated with greater OC symptoms after controlling for HA and trait negative
affect. These results suggest that similar to proposed models of cyberchondria
and HA, cyberchondria could potentially play a role in the
development/maintenance of two dimensions of OC symptoms, or vice versa. Future
work will need to determine the causal nature of these relationships or whether
they are simply co-occurring phenomena.
PMID- 26429150
TI - ESPRESSO: A novel device for laser-assisted surgery of the anterior eye segment.
AB - INTRODUCTION: Merging robotics with laser eye surgery could enhance precision,
repeatability and automation. During some eye laser procedures the patient is
awake, thus eye stabilization is desired to avoid movements that could affect the
treatment. MATERIAL AND METHODS: The ESPRESSO platform has a two-stage actuation
system to position a stabilization tool on the eye, a proximity sensing unit to
monitor the stabilization tool position, and a sensing unit to monitor the
pressure exerted on the eye. The platform is tested in-vitro and ex-vivo with
clinicians. A maximum pressure to be exerted on the eye is defined with expert
ophthalmic surgeons to be 22 mmHg: physiological intraocular pressure (IOP) range
is 10-21 mmHg. This pressure corresponds to a force of 0.3 N. RESULTS: The
necessary contact force to have eye fixation (according to the clinicians'
feedback) is evaluated: maximum values resulted always below 0.3 N. A maximum IOP
increase of 4.67 mmHg is observed, that is a slight variation with respect to the
performance of other platforms (IOP elevations up to 328 mmHg). CONCLUSION:
Design and initial assessment of the platform is presented. Eye stabilization is
performed without exceeding the critical contact force value and causing
large/sudden IOP increases.
PMID- 26429149
TI - Transoral ultrasonic total laryngectomy (TOUSS-TL): description of a new
endoscopic approach and report of two cases.
AB - The minimally invasive total laryngectomy avoids a wide surgical field and so it
has the potential benefit of reducing the local morbidity, especially on radiated
patients. This approach has been previously described on a robotic basis, the
transoral robotic total laryngectomy (TORS-TL). We have designed a minimally
invasive approach for total laryngectomy (TL) using the transoral ultrasonic
surgery technique (TOUSS). TOUSS is a transoral, endoscopic, non-robotic approach
for laryngeal and pharyngeal tumors, based on the ultrasonic scalpel as a
resection tool. Two patients with a laryngeal squamous cell carcinoma with
indication for total laryngectomy were surgically treated: one primary TL for a
subglottic carcinoma and one salvage TL with partial pharyngectomy for a local
relapse after chemoradiotherapy of a glottic carcinoma. The tumors were
completely removed with free surgical margin in both patients. The functional
recovery was satisfactory in terms of swallowing and speech (a tracheoesophageal
puncture and voice prosthesis placement were done in the same procedure). No
intraoperative complications were observed. The patient with previous
chemoradiotherapy had a pharyngocutaneous fistula which closed spontaneously
without additional surgery. We have demonstrated that transoral endoscopic
approach to the larynx and pharynx is feasible without a robotic platform. TOUSS
TL can easily spread the transoral endoscopic philosophy as well as the benefits
of a minimally invasive way to remove the entire larynx. Further research will
show the advantages in terms of complications and functional outcomes.
PMID- 26429151
TI - Thromboelastographic Clot Characteristics of Autologous Equine Blood Products
After Activation by Autologous Thrombin, Bovine Thrombin, or Calcium Chloride.
AB - OBJECTIVE: To compare clotting efficiency of platelet-rich plasma (PRP) and
concentrated platelet-poor plasma (cPPP) to citrated whole blood after activation
by autologous thrombin, bovine thrombin, or calcium chloride (CaCl2 ). STUDY
DESIGN: Experimental study. ANIMALS: Healthy adult horses (n = 6). METHODS: PRP
and cPPP were prepared by commercial devices. Using thromboelastography, clotting
variables were compared after activation of citrated autologous blood, PRP, and
cPPP by autologous thrombin, bovine thrombin, or CaCl2 , respectively. RESULTS:
PRP had the greatest clot strength and quickest clot rate, whereas cPPP had the
weakest clot strength, slowest clot rate, and longest clot initiation time.
Bovine thrombin resulted in the shortest clot initiation time, quickest clot
rate, and was similar to CaCl2 for greatest clot strength. CaCl2 also resulted in
the longest clot initiation time and time to reach maximum clot strength.
Autologous thrombin resulted in the lowest clot strength. CONCLUSION: When
combined with either bovine thrombin or CaCl2 , PRP provided the best
combinations for clinical use. Autologous thrombin was suboptimal, but could be
an autologous alternative for clinical application. As prepared here, cPPP had
inefficient clotting, but may be sufficient for plasma spray indications.
PMID- 26429152
TI - Twin pregnancy: is it a risk factor for long-term cardiovascular disease?
AB - OBJECTIVE: To investigate whether twin pregnancy increases the risk for long-term
maternal cardiovascular disease (CVD). STUDY DESIGN: A retrospective population
based cohort study compared the incidence of long-term CVD in a cohort of women
with and without a previous twin delivery. SETTING: Deliveries occurred between
the years 1988 and 2012. PATIENTS: Patients who had a twin birth between years
1988 and 2012 were included in the study, patient that had a singleton delivery
included in the control group. MAIN OUTCOME MEASURES: CVD was divided into four
categories according to severity and type. Kaplan-Meier survival curve was used
to estimate cumulative incidence of cardiovascular hospitalizations. Cox
proportional hazards model was used to estimate the adjusted hazard ratios (HR)
for CVD. RESULTS: During the study period, there were 100 387 women that met the
inclusion criteria, 4.6% (n = 4647) delivered twins at least once during the
period. The incidence of CVD was 1% in women who had a twin delivery and 1.12% in
women who had a singleton delivery. There was no difference in the cumulative
incidence of cardiovascular hospitalizations among women who had twin deliveries
as compared with singletons. When performing a Cox proportional hazard model, a
history of twin delivery did not increase the risk for long-term maternal
cardiovascular hospitalizations (adjusted HR = 1.0, 95% CI = 0.8-1.1, p = 0.698).
CONCLUSIONS: Twin pregnancy is not associated with an increased risk for long
term maternal CVD.
PMID- 26429153
TI - Identification of drug candidates and repurposing opportunities through compound
target interaction networks.
AB - INTRODUCTION: System-wide identification of both on- and off-targets of chemical
probes provides improved understanding of their therapeutic potential and
possible adverse effects, thereby accelerating and de-risking drug discovery
process. Given the high costs of experimental profiling of the complete target
space of drug-like compounds, computational models offer systematic means for
guiding these mapping efforts. These models suggest the most potent interactions
for further experimental or pre-clinical evaluation both in cell line models and
in patient-derived material. AREAS COVERED: The authors focus here on network
based machine learning models and their use in the prediction of novel compound
target interactions both in target-based and phenotype-based drug discovery
applications. While currently being used mainly in complementing the
experimentally mapped compound-target networks for drug repurposing applications,
such as extending the target space of already approved drugs, these network
pharmacology approaches may also suggest completely unexpected and novel
investigational probes for drug development. EXPERT OPINION: Although the studies
reviewed here have already demonstrated that network-centric modeling approaches
have the potential to identify candidate compounds and selective targets in
disease networks, many challenges still remain. In particular, these challenges
include how to incorporate the cellular context and genetic background into the
disease networks to enable more stratified and selective target predictions, as
well as how to make the prediction models more realistic for the practical drug
discovery and therapeutic applications.
PMID- 26429154
TI - Metal-based nanosystems for diagnosis.
AB - The impressive diversity related to etiologic factors and the distinctive genetic
and immunological behavior attained by various conditions represent the
fundamental reasons for high-rated inefficient and eventual hazardous strategies
entailed by conventional healthcare practice. Thanks to the tremendous progress
reported in nanotechnology during the last decades, various unconventional and
promising strategies have been successfully developed and examined with respect
to potential genuine biomedical applications. Given the amazing possibility to
manipulate matter at a molecular and atomic level and the incessant need to
design and implement personalized therapies, various nanosized systems have thus
been engineered. Among the newly developed nanomaterials, metallic nanoparticles
have gain attention during the intense biomedical research activity, thanks to
their peculiar size-conditioned properties. An efficient therapeutic strategy
begins with an accurate diagnosis result, so the immediate requirement of such
specific detection tools is conspicuous. The use of silver and gold in day-to-day
activities is acknowledged since ancient times, but the novel technological
opportunities extended their particular applications towards personalized
medicine. It is worthy to mention that the unexpected nanodimension-related
features of the aforementioned noble metals strongly recommend them for a large
number of current applications in nanomedicine, including novel and specific
metallic nanostructures used in diagnostics.
PMID- 26429155
TI - Current understanding of the neurobiology of major depressive disorder.
AB - Depression is highly prevalent worldwide and associated with significant
morbidity and mortality. Approximately 340 million people worldwide suffer from
depression at any given time. Based on estimates from the World Health
Organization (WHO), depression is responsible for the greatest proportion of
burden associated with non-fatal health outcomes and accounts for approximately
12% total years lived with disability. Probably no single risk factor can be
completely isolated in major depressive disorder (MDD), as interactions between
many sources of vulnerability are the most likely explanation. Buttressing the
identification of grief, demoralization, hopelessness and styles of psychological
coping of the depressed patient are vital, ongoing scientific developments that
flow from an increased understanding of this interplay amongst the immune system,
endocrine system and brain. The rapidly accumulating body of neurobiological
knowledge has catalyzed fundamental changes in how we conceptualize depressive
symptoms and has important implications regarding the treatment and even
prevention of depressive symptoms in patients.
PMID- 26429156
TI - Morphological features of melanocytic tumors with depigmented halo: review of the
literature and personal results.
AB - Halo (Sutton's) phenomenon has been described as a depigmented halo that is
associated most commonly with acquired melanocytic nevi; but it may be associated
with various types of melanocytic skin tumors, melanoma being the most
concerning. Different authors have been preoccupied with elucidating
morphological features of melanocytic tumors associated with a depigmented halo.
We reviewed the literature and discussed the main features of melanocytic halo
tumors regarding histopathological, immune microenvironment profile and
dermatoscopic appearance. We highlighted similarities and differences between
Sutton's nevus and halo melanoma, also presenting relevant aspects of our
results. Depigmented halo must be regarded as a phenomenon that may be associated
with different types of melanocytic tumors and with a broad spectrum of
histopathological atypia degree. Certain correlations between the shape,
diameter, symmetry observed in clinical examination, histopathological
appearance, dermatoscopic aspect of peritumoral halo and central tumor type could
not be established due to insufficient data and contrasting results. Further
studies are expected to add valuable information regarding the depigmented halo
tumors features.
PMID- 26429157
TI - Correlation of angiogenesis with other immunohistochemical markers in cutaneous
basal and squamous cell carcinomas.
AB - The aim of this study was to establish an immunoprofile of squamous cell
carcinoma (SCC) and basal cell carcinoma (BCC), and to explore as first time in
literature the possible correlation between maspin, DOG-1, p16 protein and
angiogenesis in these tumors. For SCCs, the histological grade of differentiation
was also taken into account. The angiogenesis was quantified in 38 randomly
selected cases of SCCs and 17 BCCc, respectively, using the antibodies vascular
endothelial growth factor (VEGF-A) and COX-2, while the microvessel density (MVD)
was evaluated with the CD31. RESULTS: In SCCs, maspin cytoplasm to nuclear shift
was an indicator of a deeper tissue invasion and dedifferentiation in the
invasion front. The poorly differentiated cases, compared to G1/G2-SCCs,
expressed more frequent the markers p16 (30.77% vs. 8%) and VEGF-A (53.85% vs.
32%), regardless the MVD. However, the p16 positivity was more frequent in BCCs
than SCCs (52.94% vs. 15.79%). All of the p16-positive carcinomas were located in
the head and neck area. DOG-1 marked 21.05% of SCCs and 5.88% of BCCs, being
directly correlated with COX-2 positivity. Eccrine glands and hair follicles also
expressed DOG-1. CONCLUSIONS: In cutaneous SCCs located in the head and neck
area, sun-dependent p16/VEGF interaction seems to be responsible by tumor
dedifferentiation, whereas maspin cytoplasm to nuclear shift might indicate a
high degree of invasiveness. This is the first report about DOG-1 positivity in
BCCs and eccrine glands, the significance of this pattern being unknown.
PMID- 26429158
TI - KRAS gene mutations - prognostic factor in colorectal cancer?
AB - The colorectal cancer (CRC) modern therapy is using adjuvant and neoadjuvant
companion therapeutic agents, part of them having an anti-angiogenic action.
Their benefic effect can be annulated by some gene mutations, which are
interfering in signal transduction pathways. One of the more frequent activating
mutations is occurring in the KRAS gene. We assessed the KRAS mutations by two
molecular methods, in a group of patients with a follow-up until 144 months,
aiming to establish eventual correlations between the presence of mutations and
the evolution of patients. We tried to appreciate the prognostic value of these
mutations. A retrospective study was conducted on 74 patients treated by radical
surgery; the surgical specimens were analyzed macroscopically and the
histopathological type and degree were established. PCR-RFLP (polymerase chain
reaction-restriction fragment length polymorphism) and pyrosequencing were
performed on paraffin-embedded tumor specimens. Statistical analysis showed
significant differences in survival between patients with wild type gene and
patients with mutation in codon 13; the same results were also obtained regarding
TNM I, II stages or Dukes type A and B cases. However, for the patients in stage
IV pTNM, the evolution was slightly better in association with a KRAS mutation
than in wild type cases.
PMID- 26429159
TI - Preliminary study of correlations between the intratumoral microvessel density
and the morphological profile of colorectal carcinoma.
AB - AIM: New blood vessel formation (angiogenesis) is a fundamental event in the
process of tumor growth and metastatic dissemination. The aim was to evaluate
intratumoral vascular density (ITMVD) and to analyze possible correlations
between ITMVD and the morphological profile of colorectal carcinoma. MATERIALS
AND METHODS: The studied group consisted of 50 patients that underwent surgery
for colorectal tumors, 12 of them receiving preoperatory radiotherapy. The
analyzed morphological parameters were tumor site, tumor gross aspect, tumor
longitudinal and transverse diameter, tumor grading, local invasion (pT),
regional invasion (pN), distant metastases (pM) and intratumoral microvessel
density (ITMVD) expressed as number of capillaries/mm2. The malignant tissue
samples were included in paraffin blocks and serial tissue sections were cut both
for Hematoxylin-Eosin staining and CD34 immunomarking. For each case, five
consecutive fields without necrosis were randomly selected with *10 objective.
Quantitative measurements were performed using special software for image
analysis. RESULTS: For non-irradiated colorectal tumors, ITMVD was the highest in
rectal localization, in infiltrative tumors, in circumferential tumors, in tumors
with low longitudinal extension, in moderately differentiated (G2) tumors and in
pT4, pN0 and pM1 tumors. DISCUSSION: Correlations showed different trends of
ITMVD depending on each parameter: ITMVD was higher when the tumor was closer to
the rectum, when it was more infiltrative, more circumferential or with low
longitudinal diameter. These trends might be exploited in defining future anti
angiogenic therapeutic strategies. CONCLUSIONS: There were some interesting
correlations between ITMVD and studied morphological parameters that have to be
validated on larger series of cases.
PMID- 26429160
TI - Toxicity of L-DOPA coated iron oxide nanoparticles in intraperitoneal delivery
setting - preliminary preclinical study.
AB - Iron oxide nanoparticles are promising candidates for theranostics in cancer,
that aims to achieve in one-step precise tumor imaging by magnetic resonance, and
targeted therapy through surface attached anti-cancer drugs. The aim of this
study was to investigate in preclinical setting the biocompatibility of new iron
oxide-based nanoparticles that were coated with L-DOPA for improved dispersion in
biological media. These nanostructures (NPs) were designed for biomedical
applications as contrast agents and/or drug carriers. We investigated the effect
exerted in vitro by NPs and L-DOPA on the viability and proliferation of normal
mouse L929 fibroblasts. NPs exhibited good biocompatibility against these cells.
Moreover, L-DOPA contained in NPs sustained fibroblasts proliferation and/or
limited anti-proliferative effects of naked nanoparticles. In the animal study,
C57BL/6 mice were injected intraperitoneally with a single dose of NPs
(approximately 125 mg/kg body weight). We followed up hematological and
histological parameters for one, three and seven days after NPs administration.
Results indicated that NPs possibly induced local inflammation and consequent
recruitment of peripheral lymphocytes, whilst the decrease of platelet counts may
reflect tissue lesions caused by NPs. The histopathological study showed mild to
moderate alterations in the hepatocytes, splenic and renal cells, while the brain
parenchyma only presented nonspecific congestive changes. Taken altogether, the
preclinical study indicated that the new iron oxide nanoparticles coated with L
DOPA were biocompatible against fibroblasts and had a convenient toxicological
profile when administered intraperitoneally in a single dose to C57BL/6 mice.
Accordingly, the proposed nanostructure is a promising candidate for imaging and
treating dispersed peritoneal tumors.
PMID- 26429161
TI - Expression pattern of beta-catenin during the development of human fetal spinal
cord.
AB - Development of the human fetal spinal cord is a very complicated process
involving numerous signaling pathways including Wnt signaling pathways. These
pathways are critical for the development and function of the mammalian nervous
system. beta-Catenin is a key molecule in the canonical Wnt signaling pathway.
However, the distributions of beta-catenin during development of the human fetal
spinal cord have not been well characterized. Therefore, in this study, we
performed immunohistochemical analysis of the beta-catenin distribution in the
developing human spinal cord from 35 fetuses at three weeks to eight months of
gestation. As early as E3W and E4W, beta-catenin was mainly expressed in the
internal limiting membrane of the neural tube and neuroepithelium (E: Embryos; W:
Weeks). During developmental stages, beta-catenin was widely expressed in various
structures and cells including the neuroepithelium, internal limiting membrane,
mantle layer, marginal layer, basal plate, alar plate, ependyma, gray matter,
white matter, neurons with multiple processes, glial cells, and nerve fibers.
This study clarifies the morphological developmental characteristics of the human
fetal spinal cord as well as the distribution and expression pattern of beta
catenin in chronological and spatial aspects. Our results suggest that the
Wnt/beta-catenin signaling pathway might play a crucial role in various stages of
the formation and differentiation of the human fetal spinal cord.
PMID- 26429162
TI - Real-time quantitative PCR detection of WT1 and M-BCR-ABL expressions in chronic
myeloid leukemia.
AB - The Philadelphia chromosome and the resulting BCR-ABL fusion gene represent the
hallmark event in chronic myeloid leukemia (CML) and their discoveries radically
changed the management of these patients. Currently Wilms tumor 1 gene (WT1) is
intensively investigated as high WT1 expression levels have been demonstrated in
case of multiple solid tumors and malignant hematological syndromes (acute
myeloid and lymphoid leukemia, myelodysplastic syndromes and chronic myeloid
leukemia). The aim of our study was to investigate the WT1 expression in CML
patients and its possible contribution to disease evolution. PATIENTS AND
METHODS: In the Laboratory of Molecular Biology, University of Medicine and
Pharmacy of Tirgu Mures, Romania, we regularly determined the M-BCR-ABL and WT1
expression levels by RQ-PCR (real-time quantitative polymerase chain reaction)
testing in case of 19 CML patients: six patients monitorized from the diagnosis
and 13 patients first tested during therapy. RESULTS: Eight CML (four advanced
stage and four CP) patients showed high WT1 expression level, and in case of 11
patients the WT1 expression levels were undetectable or lower than 0.02%. The
only significant difference between the high and low WT1 expression groups was
represented by the clinical stage. In the majority of pretreated patients (10 out
of 13 patients), the WT1 expression levels were low or undetectable. CONCLUSIONS:
High WT1 expression in CML patients is detected especially in the advanced stages
of the disease. Efficient Imatinib therapy may contribute to low WT1 levels in CP
patients.
PMID- 26429163
TI - Interplay between expression of leptin receptors and mucin histochemical
aberrations in colorectal adenocarcinoma.
AB - BACKGROUND: There is no information on the effects of leptin receptors expression
on mucin-histochemical alterations in human colorectal adenocarcinoma. AIM:
Testing the correlation of leptin receptors expression with histochemical
dysregulation of mucins in colorectal adenocarcinoma. PATIENTS AND METHODS: The
study included 75 patients with colorectal adenocarcinoma who underwent surgical
resection. Following a routine histopathological tissue analysis, 3-4 MUm thick
cuts were made onto resected tumors, which underwent a routine Hematoxylin-Eosin,
histochemical Alcian Blue-Periodic Acid Schiff, pH 2.5, and High Iron Diamine
Alcian Blue, pH 2.5, methods for mucin differentiation and immunohistochemical
Avidin-Biotin peroxidase complex method with anti-Ki67 and anti-leptin receptor
antibodies. Following the quantification of results for the statistical analysis,
the statistical software package SPSS for Windows (13.0) was used, and the tests
for analyzing the significance of differences and correlation analysis -
Spearman's rank correlation coefficient, were conducted. RESULTS: Increased
expression of leptin receptors is with highly significant correlation coefficient
associated with hypersecretion of sialomucins. Significant positive correlation
coefficient exists between the leptin receptors expression against neutral
fucomucins secretion. With weak and negative, but a significant correlation
coefficient, leptin receptors expression is associated to the sulfomucins
generation. CONCLUSIONS: Increased expression of leptin receptors in colorectal
adenocarcinoma is associated with mucin-histochemical abnormalities that are
manifested by sialomucins hypersecretion and reduction, ultimately resulting in
the absence of sulfomucins secretion.
PMID- 26429164
TI - c-abl and YWHAZ gene expression in gastric cancer.
AB - This study aims to determine the gene expression for c-abl and YWHAZ in gastric
cancer and the differences between the c-abl and YWHAZ gene expression inside the
tumor versus healthy tissue (at the resection edges). This prospective study
included 34 patients with gastric neoplasia, 21 men and 13 women, aged between 49
and 79 years (65.5 years median). After the surgical procedure, in these cases,
we collected two tissue samples: one sample was obtained from inside the tumoral
tissue and another sample from the gastric tissue, which was identified as normal
apparently, as far as possible from the tumor (resection edge). For determining
the c-abl and YWHAZ gene expression, we used the quantitative real-time
polymerase chain reaction. Regarding the c-abl gene expression in gastric cancer,
c-abl expression was identified as lower inside tumor cells comparing to the
normal gastric tissue (resection limit). This difference of gene expression
emphasize the role of the c-abl gene in normal tissue growth and the involvement
in apoptosis induction when alteration of DNA occurs, as a result to different
agents actions as stress, ionizing radiations. The loss of expression or even the
down-regulation of the c-abl is a fundamental event that leads to genesis and
progression of tumors. No significant differences of the YWHAZ gene expression
between the tumoral and normal gastric tissue probes were recorded in our study.
PMID- 26429165
TI - Enhanced expression of vascular endothelial growth factor and increased
microvascular density in women with endometrial hyperplasia: a possible
relationship with uterine natural killer cells.
AB - This case-control study aimed to investigate the expression of natural killer
cells (NKCs) and the integrated optical density (IOD) of vascular endothelial
growth factor (VEGF) and to quantify microvascular density (MVD) in endometrial
biopsies from women with endometrial hyperplasia (EH) relative to normal
subjects. Histological data from four groups were analyzed. The study population
included 30 women with simple EH without atypia, 25 patients with complex EH
without atypia, 25 with complex EH with atypia and 25 healthy women with non
hyperplastic endometrium (control group). Paraffin sections were immunostained
with antibodies against CD56, VEGF-A and CD34 using an Avidin-Biotin-Peroxidase
technique. The evaluation of NKC density and IOD of VEGF expression and
measurement of MVD were performed using light microscopy examination and image
analysis techniques. Increased numbers of NKCs were documented in cases of
complex EH with atypia compared with the other groups (p<0.001). The number of
NKCs was lower in cases of hyperplasia without atypia compared with the controls,
but the difference was not significant. The IOD of VEGF-A and MVD increased
significantly with progression from the non-hyperplastic endometrium through the
three groups of EH (p<0.001). We observed a significant correlation between the
MVD and the IOD of VEGF-A in the studied groups (r=0.434; p<0.001). Additionally,
NKCs density was correlated significantly with IOD of VEGF-A (r=0.661; p<0.001)
and with the MVD (r=0.473; p<0.001). These results suggest that NKC-count, IOD of
VEGF and endometrial MVD are all related to the histological changes of the
endometrium and that endometrial hyperplasia exhibits distinct immunological
backgrounds in the context of NKC infiltration and VEGF production.
PMID- 26429166
TI - A hardware approach for histological and histopathological digital image stain
normalization.
AB - Advances in technology made the migration of pathological diagnosis to digital
slides possible. As the need for objectivity and automation emerged, new computer
software algorithms were proposed. Computer algorithms demand accurate color and
intensity values in order to provide reliable results. The tissue samples undergo
several processing steps from histological preparation to digitalization, which
cannot be completely standardized. Thus, non-standardized input data generates
unreliable output data. In this article, we discuss a new computational
normalization algorithm for histopathological stained slides that uses a hardware
color marker. The marker is added to the glass slide together with the tissue
section, exposed to all the processing steps and altered in the same manner as
the biological material of interest, thus becoming a solid color marker for image
normalization. The results of the proposed method are numerically and
perceptually tested in order to prove the advantages of the method. We conclude
that our combined hardware-software technique for staining normalization of
digital slides is superior to the existing methods based on only software
normalization, and that its implementation will tackle not only the acquisition
errors but also the technical errors that may occur during the staining process.
PMID- 26429167
TI - Ovariectomized rats' femur treated with fibrates and statins. Assessment of pore
size distribution by 1H-NMR relaxometry.
AB - The effects of two wonder drugs, simvastatins and fenofibrates on the proximal
part of the femoris of a series of ovariectomized and non-ovariectomized Wistar
albino rats was estimated qualitatively and semi-quantitatively by the modern
method of 1D 1H-NMR T2-distribution. The 72 rats subjected to this study were
divided in six groups and were sacrificed at two, four, six and eight weeks after
ovariectomy and the proximal part of femoris was harvested. The CPMG (Carr
Purcell-Meiboom-Gill) echoes train curves were measured for the bones fully
saturated with water during two months after two months of natural drying. These
decays were analyzed by Laplace inversion and an average of normalized T2
distributions was considered for all rat's groups. The 1D averaged T2
distributions present four peaks, which were associated with protons in four
major environments, from which the free water protons are used as spy molecules
to explore the boundaries of cavities. In the approximation of spherical pores,
the averaged T2-distributions were transformed in distributions of pores
diameters. These were found in the range from 2 MUm up to 2 mm. The relative
amplitudes, widths and position of deconvoluted distributions of small, medium
and large cavities are used for a qualitatively analysis of the effect of our
lipid-lowering drugs. For a semi-quantitatively analysis, we chose the diameter d
of proximal part of femoris' trabecular cavities. We show that the positive or
negative effects of treatments with simvastatins and fenofibrates are strongly
dependent on the duration of treatment. Moreover, the treatment of healthy bone
is generally counter-indicated.
PMID- 26429168
TI - The assessment of lower face morphology changes in edentulous patients after
prosthodontic rehabilitation, using two methods of measurement.
AB - Using two measurement methods (a three-dimensional laser scanning system and a
digital caliper), this study compares the lower face morphology of complete
edentulous patients, before and after prosthodontic rehabilitation with
bimaxillary complete dentures. Fourteen edentulous patients were randomly
selected from the Department of Prosthodontics, at the Faculty of Dental
Medicine, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
The changes that occurred in the lower third of the face after prosthodontic
treatment were assessed quantitatively by measuring the vertical projection of
the distances between two sets of anthropometric landmarks: Subnasale - cutaneous
Pogonion (D1) and Labiale superius - Labiale inferius (D2). A two-way repeated
measures ANOVA model design was carried out to test for significant interactions,
main effects and differences between the two types of measuring devices and
between the initial and final rehabilitation time points. The main effect of the
type of measuring device showed no statistically significant differences in the
measured distances (p=0.24 for D1 and p=0.39 for D2), between the initial and the
final rehabilitation time points. Regarding the main effect of time, there were
statistically significant differences in both the measured distances D1 and D2
(p=0.001), between the initial and the final rehabilitation time points. The two
methods of measurement were equally reliable in the assessment of lower face
morphology changes in edentulous patients after prosthodontic rehabilitation with
bimaxillary complete dentures. The differences between the measurements taken
before and after prosthodontic rehabilitation proved to be statistically
significant.
PMID- 26429169
TI - The storage period of the formalin-fixed paraffin-embedded tumor blocks does not
influence the concentration and purity of the isolated DNA in a series of 83
renal and thyroid carcinomas.
AB - Optimal recovery of nucleic acids from formalin-fixed paraffin-embedded (FFPE)
tissues is highly dependent on a series of pre-extraction steps, mainly related
(but not limited) to fixation. The aim of our study was to investigate if the
storage period of the FFPE blocks had a significant effect on the isolated DNA.
We examined the quantity and purity of the isolated DNA from 83 FFPE blocks,
corresponding to malignant thyroid (n=28) and renal (n=55) carcinomas that had
been stored in our department for up to eight years. The DNA extraction protocol
was based on a precipitation method (MasterPureTM DNA Purification Kit,
Epicentre), in accordance to the manufacturer instructions, optimized in our
laboratory. A spectrophotometer was used to determine the yield (A260) and purity
(A260/A280 ratio) of the isolated DNA. We successfully isolated good DNA quantity
and purity from all our study cases (mean concentration: 223.4 +/- 104.16 ng/MUL;
mean A260/A280 ratio: 1.68 +/- 0.09). Moreover, no statistically significant
differences were observed between tumor blocks stored for 2-3 years and 7-8
years, respectively, both in terms of DNA quantity (p=0.196) and purity
(p=0.663). In conclusion, we successfully validated an efficient, reproducible
DNA extraction technique that provided a good range of DNA concentrations and
purity, regardless the type of tissue (thyroid or kidney). Moreover, we
demonstrated that the storage period of the FFPE blocks does not have a
significant influence on the DNA quantity and purity.
PMID- 26429170
TI - Etiopathogenic, therapeutic and histopathological aspects upon the anterior
vaginal wall prolapse.
AB - The pelvine organ prolapse (POP) is a condition affecting million of women, with
a major impact upon the social and professional life of the patients. According
to various studies, it affects approximately 40% of the women aged over 50 years.
About 10% of women with POP require a surgical procedure for POP or urinary
incontinence. Our study comprised a number of 14 patients, aged between 55 and 70
years, hospitalized and treated in the Clinic of Urology within the Emergency
County Hospital of Craiova, Romania, between 2011 and 2013, for second-degree
cystocele. Of these, 11 (78.57%) patients had more than two natural deliveries,
10 suffered more than three abortions, and eight (57.14%) women suffered from
obesity. The increase of abdominal pressure, induced by chronic coughing,
constipation or hard physical work, was identified in more patients. Thus, six
(42.8%) patients presented chronic bronchitis, four (28.57%) patients were
smokers, eight (57.14%) patients presented chronic constipation, and 10 (71.42%)
patients stated that they had performed hard physical work. The presence of
effort urinary incontinence, associated to the cystocele, was found in eight
(57.14%) cases. The surgical intervention consisted in the performance of a
direct cystopexia with a synthetic tent, placed in a transobturatory way, in a
"tension free" manner (Perigee System). The post-operatory evolution was a good
one; the results after six months showed that 12 (85.71%) women were cured, two
(14.29%) cases of cystocele relapsed, while in two patients there maintained the
effort urinary incontinence. The histopathological examination of the anterior
vaginal wall fragments, harvested during the surgical intervention, showed the
presence of a chronic inflammatory infiltrate in the lamina propria of the
uterine mucosa, which may cause the post-operatory relapses. We consider that the
reduction of the inflammatory process through the administration of anti
inflammatory drugs could reduce the POP onset and progress.
PMID- 26429171
TI - Electron microscopic aspects of the effects of certain prostaglandin analogs on
mouse testes.
AB - Prostaglandins were highlighted in the seminal plasma and then in the rest of the
male and female genital tract. Prostaglandin analogs, firstly used in obstetrics
and gynecology, are now widespread in both sexes, especially in the treatment of
gastric and duodenal ulcers, glaucoma, etc. Therefore, we tried to highlight the
effects of repeated administration of Cloprostenol and CIPG isopropyl ester (both
prostaglandin F2alpha analogs) for the male gonad. In our experiment, we used
Cloprostenol and CIPG isopropyl ester. We used three groups of white, male mice,
aged 50-80 days, kept in standard laboratory conditions, which received the same
feed. Each group included 12 mice. The first batch was the control group and
received no substance at all. The second batch received 25 MUg/kg of Cloprostenol
dose per body per day, intraperitoneal administration (a single dose per day) on
a daily basis for a four weeks period of time. The third batch received a 25
MUg/kg CIPG isopropyl ester dose per body/day intraperitoneal administration (a
single dose per day) on a daily basis for a four weeks period of time. After 7,
14 and 28 days of treatment, we sacrificed four animals in each of the batches by
cutting their carotid arteries. The prostanoid analogs we used, Cloprostenol and
CIPG isopropyl ester, have similar actions on male gonad in mice. These analogs
induced significant changes in the evolution of the spermatogenesis and
spermiogenesis. In relation to the treatment duration there were cellular changes
suggesting apoptosis in different stages. With regard to spermiogenesis, the
ultrastructural aspects indicate a decrease of the sperm structuring processes,
especially in the acrosomal apparatus and chromatin.
PMID- 26429172
TI - Vascular calcification in continuous ambulatory peritoneal dialysis patients.
AB - Vascular calcifications represent a severe complication of secondary
hyperparathyroidism in patients with chronic kidney disease (CKD) stage 5. The
factors influencing the development of this complication are in close relation
with the pathology of chronic dialysis premorbid condition, and with therapy as
well. The present article highlights the association between several factors and
the development or the aggravation of vascular calcifications in continuous
ambulatory peritoneal dialysis (CAPD) patients. The results are not always in
accordance with similar literature data, but there is a lack of researches
regarding mineral metabolism in peritoneal dialysis patients versus those on
chronic hemodialysis.
PMID- 26429173
TI - Studies regarding the protective effects exhibited by antidepressants on cell
models.
AB - The study aimed to assess in vitro the short-term effects exerted by fluoxetine,
sertraline and venlafaxine on certain physiological properties in two different
study models: U937 monocytes and erythrocytes isolated from patients treated with
the above-mentioned molecules. Results on U937 cell suspensions revealed the
depolarization of the cell membrane induced by the three antidepressants. The
maximal depolarization effect was registered after 15 minutes of cell exposure
and was concentration-dependent, in a non-monotonic manner. The effect was also
dependent on the tested compound, fluoxetine presenting the strongest
depolarizing effect compared to sertraline and venlafaxine. The erythrocyte
susceptibility to lipid peroxidation and glucose-6-phosphate dehydrogenase
activity were assessed on red blood cells isolated from patients with depressive
disorder. Our results revealed that antidepressant treatment induced the
antioxidant defense, by decreasing erythrocyte susceptibility to lipid
peroxidation and increasing glucose-6-phosphate dehydrogenase activity. The
effect is more intense in the case of severe pathology and less evident in the
case of moderate or minor disorder, as expressed by MADRS (Montgomery-Asberg
Depression Rating Scale) score. Our results could indicate that selected
antidepressants at therapeutic concentrations, besides their known
pharmacological effects, exhibit a protective effect against oxidative stress and
also influence cells with immune properties.
PMID- 26429174
TI - Histological and immunohistochemical aspects of papillary thyroid cancer.
AB - Papillary thyroid carcinoma is one of the most common malignancies of the
endocrine system. In recent years, its incidence has increased worldwide,
including children, which concerns the entire community. Although the
histopathological diagnosis seems rather easy, the existence of particular forms
of thyroid cancer and the inclusion of the follicular aspect as a variant of
papillary carcinoma lead to diagnostic confusion. Therefore, in the last 20 years
were reviewed several immunohistochemical markers, which are useful in the
positive and differential diagnosis, and which offer better data on disease
prognosis. Our study included a total of 27 cases of papillary carcinomas, which
we evaluated the immunohistochemical expression of Ki-67, p53, p63, E-cadherin,
CD56, calretinin, and bcl-2 markers. The most intense expression was found in
p53, E-cadherin, and bcl-2. Ki-67 and p63 expression were moderate and
inconsistent, and CD56 and calretinin had a negative expression in all cases.
PMID- 26429175
TI - Histological differences between laser-assisted and suction-assisted lipoplasty
aspirates - a comparative study.
AB - INTRODUCTION: The authors aimed to assess the histological differences between
the traditional suction-assisted lipoplasty (SAL) and the more recently developed
laser-assisted lipoplasty (LAL) aspirates, in a 20-case comparative study.
PATIENTS AND METHODS: Between March of 2011 and March of 2012, we operated on 20
healthy female patients seeking body contouring procedures of the abdomen, flanks
and outer thighs, all having good to moderate skin tone and moderate to heavy
adipose deposits and no previous treatment of the interested areas. After initial
aspiration of a 100 mL sample of fat tissue through the SAL technique, we applied
the LAL protocol, using a Lipolite device with a 1064 nm Nd:YAG laser, again
sampling the aspirate for histological study. RESULTS: The analyzed samples
revealed significant histological difference between the two aspirates: the
adipose tissue architecture, after conducting the LAL procedure, appeared to be
disrupted, consisting of deformed and ruptured fat cells surrounded by
coagulation-modified collagen, small lymphocytic inflammatory infiltrate,
coagulated small blood vessel and intact nerves. In contrast, the cytological
patterns of the adipose tissue after using the SAL technique resembled normal fat
tissue structure. CONCLUSIONS: Our study succeeded in demonstrating significant
histological differences between SAL and LAL aspirates, many of which could
explain certain disparities between the clinical outcomes of the two procedures.
PMID- 26429176
TI - Histological and immunohistochemical study of the eyelid basal cell carcinomas.
AB - The eyelids represent a frequent site for numerous malignant tumors, which
generally present subtle symptoms or can imitate benignant tumors. Our study was
carried on 80 patients, 48 males and 32 females aged between 48 and 92 years. The
patients were hospitalized in the Ophthalmology Clinic of the Emergency County
Hospital of Craiova, Romania. The study was conducted over five years, between
2010 and 2014. Our study included 80 basal cell carcinomas of the eyelids, of
which 48 (60%) were nodular basal cell carcinomas, 15 (18.75%) were adenoid basal
cell carcinomas, 10 (12.5%) were cystic and seven (8.75%) were morpheaform basal
cell carcinoma. Our study showed a moderate expression of bcl-2 marker in the
nodular type of basal cell carcinoma and a high expression in the other
histopathological types, thus inducing an increased malignancy comparing to the
nodular type. E-cadherin was absent in nodular, cystic and adenoid basal cell
carcinomas and had a moderate expression in morpheaform basal cell carcinoma.
Morpheaform and adenoid types presented 20% expression of Ki67 of the malignant
cells nuclei, while the cystic type presented Ki67 expression in less than 10% of
the malignant cells nuclei. Due to high morbidity and increasing incidence, basal
cell carcinoma of the eyelid represents an important health issue nowadays.
PMID- 26429177
TI - Chondrosarcoma of the hyoid bone: a case report.
AB - Chondrosarcoma is a malignancy of the mesenchymal tissue derived from transformed
cells that produce the cartilage matrix. In the neck area, it represents less
than 0.5% of malignant tumor pathology. Chondrosarcoma of the hyoid bone is
extremely rare, only 20 cases having been published so far (PubMed 2014). We
present the case of a 30-year-old patient from the urban area, admitted in the
ENT (Ear, Nose & Throat) Emergency Service with inspiratory dyspnea, dysphagia,
stomatolalia, with evolutive and progressive clinical history of 2-3 months.
Endoscopic examination revealed a pharyngolaryngeal tumor process located in the
right vallecula, who by mass effect displaces the above-hyoid epiglottis. CT
(computerized tomography) scan described a cervical polycystic tumor aspect, with
multiple septae and inside calcifications with a diameter of 3-4 mm. Surgery
consisted in removal of the tumor process together with the hyoid bone.
Histopathological and especially immunohistochemical examination established the
diagnosis of low-grade chondrosarcoma of the hyoid bone. For assessment of the
phenotype of the tumor cells, the following immunohistochemical markers were
used: p53, Ki67. The patient followed radiochemotherapic oncological treatment
and returned for regular follow-ups. There was a positive development with no
signs of regional or remote relapse or metastasis for 24 months after surgical
treatment. Surgery is the treatment of choice, with complete removal of the
tumor, with chemoradiation playing an adjuvant role. Regular tracking of the
patient is mandatory.
PMID- 26429178
TI - A challenging case of ocular melanoma.
AB - Ocular melanoma is a rare malignancy found in clinical practice. In this paper,
we present a case of highly aggressive ocular melanoma, which was surgically
removed at the Department of Ophthalmology and diagnosed at the Department of
Pathology, Emergency University Hospital, Bucharest, Romania, using conventional
histopathological techniques. Uveal melanoma, a subset of ocular melanoma, has a
distinct behavior in comparison to cutaneous melanoma and has a widely divergent
prognosis. Approximately half of patients with ocular melanoma will develop
metastatic disease, predominantly with hepatic, pulmonary or cerebral location,
over a 10 to 15 years period. No systemic therapy was associated with an evident
clinical outcome for patients with advanced disease and overall survival rate
remains poor.
PMID- 26429179
TI - Congenital solitary kidney with multiple renal arteries: case report using MDCT
angiography.
AB - A congenital solitary kidney with multiple renal arteries is a rare congenital
abnormality that can occur in the presence of multiple other anomalies. We
describe an atypical case of a right congenital solitary kidney with three renal
arteries (RA) one main RA and two additional renal arteries in a 75-year-old
woman with uterine didelphys. The main RA had an intraluminal diameter larger
than the diameter of the additional renal arteries (AdRAs) at the origin (0.53 cm
for the main RA; 0.49 cm and 0.32 cm for the two AdRAs). Both the AdRAs had a
greater length than the main RA (3.51 cm for the main RA; 3.70 cm and 4.77 cm for
the two AdRAs). The calculated volume of the kidney was 283 cm3, while the volume
of the renal parenchyma was 258 cm3. Knowledge of this variant is extremely
important in clinical practice as it has been found to be associated with
proteinuria, hypertension and renal insufficiency.
PMID- 26429180
TI - Solitary trichoepithelioma: clinical, dermatoscopic and histopathological
findings.
AB - Trichoepithelioma is part of the adnexal carcinomas. It is a benign, small tumor,
usually under a centimeter in diameter, which develops in the basal cells of the
hair follicle. CASE REPORT: We present the case of a 30-year-old female patient,
from rural area, which was hospitalized in the Clinic of Dermatology, Emergency
County Hospital, Craiova, Romania, in March 2015, for the presence of a skin
tumor, with round-oval shape, 0.5 cm in diameter, brownish colored, located on
the left cervical region. The patient had no past medical history. The skin tumor
appeared two years ago, and it was slowly increasing in size. Physical
examination was in normal ranges. The dermatoscopic examination reveal a pearly
white background covered with tumor islands that were oval shaped, with
hyperpigmentation, centered by keratin cysts and surrounded by collagen. During
hospitalization, we performed tumor biopsy. The histopathological examination
showed microscopic structure of trichoepithelioma. After history taking, physical
examination, dermatoscopic examination and histopathological result, our
diagnosis was left cervical trichoepithelioma. CONCLUSIONS: Trichoepithelioma is
a rare trichogenic tumor, which appears at any age, including newborns, with
potential for local recurrence. Our case report represents a classic
dermatoscopic aspect of trichoepithelioma, that can have close resemblance to
basal cell carcinoma and other skin adnexal tumors, clinically, dermatoscopic and
histopathological.
PMID- 26429181
TI - A rare case of concomitant tuberculosis of the nose, paranasal sinuses and
larynx: clinical, histological and immunohistochemical aspects. A case report.
AB - Extrapulmonary tuberculosis is a rare condition determined by Mycobacterium
tuberculosis. It can affect any organ, and has a higher incidence with the
increase of HIV infection, or in countries with high pulmonary tuberculosis.
Diagnosis is difficult, mostly because of non-specific symptoms and a low rate of
presentation for medical consult when symptoms do occur. Complete diagnosis is
usually set by histological, immunohistochemical examinations, and also with
Polymerase Chain Reaction (PCR) in selected cases. The authors present a case of
concomitant tuberculosis of the nose, paranasal sinuses and subglottic larynx,
without primary involvement of the lungs. The diagnosis was imposed by
histological examination and immunostaining of probes obtained in surgery. The
treatment was surgical debridement followed by specific antituberculosis
medication.
PMID- 26429182
TI - Low-grade appendiceal mucinous neoplasm mimicking an adnexal mass.
AB - We present a rare case of malignant epithelial neoplasm of the appendix, an
uncommon disorder encountered in clinical practice, which poses a variety of
diagnostic and therapeutic challenges. We report a particular case in which the
appendix was abnormally located in the pelvis, mimicking an adnexal mass.
Therefore, it was difficult to make the preoperative diagnosis on clinical
examination, imaging studies and laboratory tests and we discovered the lesion
during the diagnostic laparoscopy. No lymphadenopathy or mucinous ascites were
found. The case was completely handled via the laparoscopic approach keeping the
appendix intact during the operation. The frozen section, the detailed
histopathology overview as well as multiple immunostaining with a complex panel
of markers report diagnosed a low-grade appendiceal mucinous neoplasm (LAMN) with
no invasion of the wall. No adjuvant therapy was considered needed. At a one-year
follow-up oncological assessment, the patient was free of disease. In women with
cystic mass in the right iliac fossa an appendiceal mucocele should be considered
in the differential diagnosis. Laparoscopic appendectomy can represent an
adequate operation for the appendiceal mucinous neoplasm if the histological
report is clear and surgical precautionary measures are taken.
PMID- 26429183
TI - Inflamed molluscum contagiosum in a 6-year-old boy: a case report.
AB - The precise prevalence of molluscum contagiosum (MC) is still unknown. The
pediatric studies showed a cumulative incidence of 17% in children less than 15
years, but there are no studies available for Romania. The papular skin lesions
are generally less than 5 mm, but the immunocompromised patients may develop
large uncommon lesions. The pediatric cases are located mostly on the limbs,
trunk or the face. The lab investigations are not usually required because the
clinical features are typical. A biopsy followed by a light microscopy may help
in some cases. We are presenting the case of a 6-year-old boy suffering from MC
since almost a year. When examined in our clinic, the child developed 2 to 4 mm
dome-shaped flesh-colored papules with central umbilication on his trunk
diagnosed as MC. The microscopic examination revealed bud-like proliferation of
the epidermis, molluscum bodies and moderate chronic inflammation of the dermis.
In about one month of treatment, all the lesions disappeared without other local
or general complications.
PMID- 26429184
TI - Necrotizing fasciitis in oro-maxillo-facial area after radiotherapy for squamous
cell carcinoma of the soft palate.
AB - The fascia's and subcutaneous adipose tissue's impairment by mono or
polymicrobial infection, which also can involve the skin and the muscles, is
rarely seen in oro-maxillo-facial area. The present case report is presenting a
case of necrotizing fasciitis in a patient who had a history of an invasive
squamous cell carcinoma of the soft palate, with surgical treatment and with
radiotherapy. He was admitted in our Clinic with malaise and subsequently
developed a toxico-septic shock. Clinical symptoms, serological and
bacteriological analysis and histopathological examination confirmed the
diagnosis of necrotizing fasciitis (NF). The patient subsequently underwent a
series of surgical reconstruction and aesthetic treatments because of the
complications that had arised in the meantime. Postoperative evolution was
favorable towards complete closure of the defect. The prognosis of this disease
is generally reserved, the favorable evolution depending on the possibility of
wound sterilization and the surgery is required despite its mutilating effect.
PMID- 26429185
TI - Early intrauterine development of mixed giant intracranial teratoma in newborn: a
case report.
AB - Teratoma is one of the most frequent fetal intracranial tumors, but it usually
grows very quickly and the fetus is generally a stillborn. Rare cases have slow
development or are located in areas that afford immediate surgery after birth
with variable chances of survival. Even more rare cases survive days or weeks,
but with no chance of surgical treatment and with prolonged palliative care. We
present a 34 weeks premature infant, born by C-section with a giant intracranial
tumor, whose origin could not be ascertained, occupied almost all-intracranial
space and survived 25 days with supportive care. The histological examination
established a G3 mixed teratoma, predominantly with immature cells from all three
embryonic layers. The cerebellum was normal and infra-mesencephalic structures
were present. The infant presented with severe anemia and mild respiratory
distress, and was out of neurosurgical therapeutic resources. Antenatal
examination was normal until 30 weeks, when fetal ultrasound described a degree
of hydrocephalus, but no tumor was individualized. CONCLUSIONS: G3 type complex
teratoma, even rare, can be localized at cerebral level and get giant development
and growth only in the third trimester of pregnancy, ending with a neonate that
has no chance of survival. Such cases cannot benefit of therapeutic interruption
of pregnancy and generate serious difficulties for parents and clinicians.
PMID- 26429186
TI - Neuroendocrine tumor arising de novo in the left upper thigh: a case report.
AB - Neuroendocrine tumors (NETs) originate in the neuroendocrine cells of the neural
crest (Kulchitsky cells). If neuroendocrine tumors arising in the digestive tract
or lung may occasionally result in skin metastases, primary soft tissue or skin
NETs are infrequent. The current paper presents the case of an elderly woman
patient with neuroendocrine tumors arising de novo in the left upper thigh,
accompanied by lymph nodes metastases in the left groin and in the left pelvic
sidewall, in close vicinity of the iliac vessels. The diagnosis of NET was
performed based on immunohistochemical tests. Such tumors show a slow growth and,
generally, have a good prognosis. It is emphasized that complete surgical
excision, in some cases associated with adjuvant external radiotherapy is the
optimal therapeutic modality in dealing with such lesions.
PMID- 26429187
TI - Fenestration of the middle cerebral artery in a patient who presented with
transient ischemic attack.
AB - Cerebral artery fenestrations are usually detected incidentally during
angiography, have a reported incidence ranging from of 0.03% to 1%, and rarely
cause neurological symptoms. They can, however, be associated with aneurysmal
dilatation at the proximal or distal end of the fenestration, cerebral
arteriovenous malformations, or (rarely) ischemic symptoms. We present a case of
a 54-year-old obese woman who presented with a large convex-lens-like
fenestration of the right middle cerebral artery (MCA) at the M1 segment (distal
to the origin of the temporopolar artery) associated with a transient ischemic
attack. The MCA fenestration caused a local change in hemodynamic blood flow,
which leads to cerebral ischemia. Magnetic resonance angiography (MRA) also
revealed an associated small slit-like fenestration of the basilar artery (BA),
hypoplasia of the A1 segment of the right anterior cerebral artery, bilateral
fetal posterior cerebral arteries, and bilateral absence of the posterior
communicating arteries. To our knowledge, this is the sixth reported case of MCA
fenestration with an associated ischemic attack. In our case, fenestrations of
the MCA, the BA, and hypoplasia of the A1 segment of ACA were not associated with
any aneurysms.
PMID- 26429188
TI - Prosthodontic management of an extreme atrophy of the mandible correlated with a
prominent genial tubercle - a clinical report.
AB - Extreme atrophy of the mandibular alveolar crest can pose a great prosthodontic
challenge, especially when the genial tubercles remain as a bony projection in
the floor of the mouth. This article is a clinical report on the prosthodontic
management of a severe mandible atrophy correlated with a prominent genial
tubercle. A complete denture was carefully designed and fabricated in order to
restore both the function and esthetics of the patient.
PMID- 26429189
TI - Choriocarcinoma developed in a tubal pregnancy - a case report.
AB - Carcinoma of the Fallopian tube is the least frequent tumor of the female genital
tract. The diagnosis is difficult but could be made more frequently if the causes
of abnormal bleeding were thoroughly investigated by means of cytology and
endometrial curettage. Treatment is by resection of the tumor, total
hysterectomy, and bilateral salpingo-oophorectomy followed by chemotherapy. A 25
year-old patient, presented herself at the emergency room, accusing intense lower
abdominal pains, accompanied by vaginal bleeding. The histological aspect
corroborated with the Ki-67 index is strongly suggestive for a choriocarcinoma
developed in a tubal ectopic pregnancy.
PMID- 26429190
TI - An unusual duplication of the inferior vena cava in a patient with endovascular
repair for abdominal aortic aneurysm.
AB - A 66-year-old Caucasian male, with sensation of abdominal pulsation was admitted
to our hospital. In multidetector 64-row computed tomography (CT) angiography, an
abdominal aortic aneurysm was observed. Endovascular aortic repair was performed.
Control CT confirmed prosperity with stent graft fixation and absence of any
vascular complications. Investigation also showed asymmetrical duplication of the
inferior vena cava (IVC). Right (RIVC) and left (LIVC) inferior vena cava arose
from the confluence of the right and left iliac veins. The LIVC continued as left
renal vein.
PMID- 26429191
TI - Waardenburg syndrome type 2: an orthodontic perspective.
AB - Waardenburg syndrome is a rare form of neurocristopathy. It is a disorder in the
development of neural crest cells, caused by an altered cellular migration during
the embryonic phase. That alteration causes an association of different
abnormalities such as pigmentary disturbances of the hair, iris, skin, stria
vascularis of the cochlea, dystopia canthorum and sensorineural hearing loss. We
report a case of a 14-year-old Romanian male, with a family history of
Waardenburg syndrome (mother) and Usher syndrome (father - congenitally
sensorineural hearing loss and retinal degeneration). The case particularities
are: the correlation between malocclusion and Waardenburg syndrome due to
hypoplastic alae nasi and also factors that produced hearing loss, which could be
Waardenburg syndrome, Usher syndrome or the presence of the connexin 26 (W24X)
gene mutation.
PMID- 26429192
TI - Ethical issues in therapeutic endoscopy - can communication between patient and
physician make a difference?
AB - Therapeutic endoscopy represents a major step in evidence-based medicine with
great potential in the evolution of non-invasive surgery. The evolutionary status
of endoscopy has reached a level where some of the surgical intervention can be
performed in a minimal invasive way, with great benefits for the patient.
However, this rises up some ethical issues regarding the patient's comfort zone,
possible risks and complications and subjected the physician to possible
litigation situations if not well trained. A rather good interaction and
communication between patient and endoscopist is mandatory, as the health-care
experience might be more satisfying. Unfortunate situations may also be avoided
if intensive training and up to date knowledge and skills are acquired before
jumping to therapeutic endoscopy. The continuous development and general focus on
interventional endoscopy seems to have a key role on current medical standings.
Therefore, in the following paper we have tried to underline the potential
ethical problems that both the patient and the physician should take into
consideration towards a better therapeutic endoscopic result.
PMID- 26429193
TI - Protective Effects of UCF-101 on Cerebral Ischemia-Reperfusion (CIR) is Depended
on the MAPK/p38/ERK Signaling Pathway.
AB - This study was aimed to investigate the treatment mechanisms of 5-[5-(2
nitrophenyl) furfuryliodine]-1,3-diphenyl-2-thiobarbituric acid (UCF-101) in
cerebral ischemia-reperfusion (CIR) model rats. Total of 54 healthy male Wistar
rats were randomly assigned into three groups, namely sham group, vehicle group,
and UCF-101 group. The CIR-injured model was established by right middle cerebral
artery occlusion and reperfusion. Neurological function was assessed by an
investigator according to the Longa neurologic deficit scores. Meanwhile, the
cerebral tissue morphology and apoptotic neurons were evaluated by H&E and TUNEL
staining, respectively. Additionally, the expressions of caspase 3, p-p38, and p
ERK were detected by immunohistochemistry or/and Western blotting assays. As
results, neurologic deficit and pathological damage were obviously enhanced and
TUNEL positive neurons were significantly increased in CIR-injured rats, as
compared with those in sham group. Furthermore, the expressions of caspase 3, p
p38, and p-ERK were also significantly increased in vehicle group than those in
sham group (P < 0.05). However, UCF-101 treatment could markedly weaken the
neurologic deficit with lower scores and improve pathological condition. After
UCF-101 treatment, TUNEL positive neurons as well as the expression of caspase 3
were significantly decreased than those in vehicle group (P < 0.05). Besides, p
p38 was decreased while p-ERK was increased in UCF-101 group than those in
vehicle group (P < 0.05). Therefore, we concluded that the protective effects of
UCF-101 might be associated with apoptosis process and MAPK signaling pathway in
the CIR-injured model.
PMID- 26429194
TI - Appropriate experimental approach is critical for identifying neurotransmitter
substances: application to enteric purinergic neurotransmission.
PMID- 26429195
TI - Response to Mutafova-Yambolieva and Sanders.
PMID- 26429196
TI - ["I do the right thing only against payment": A critique of pay for performance
in psychiatry].
AB - This paper takes a critical look at pay for performance (P4P) as a model for
introducing new incentives in psychiatry. This model is to be seen as a tool of
commercialism, and such a restructuring of psychiatry represents a wide-reaching
political maneuver which actively introduces economical parameters into the field
and will have a great impact on psychiatry. P4P starts with the false premise
that medicine has to be structured like industry. This premise is false because
psychiatry has to do with relationships to patients, and not with the production
of a product. Therefore, it is essential to reflect critically upon the premises
and consequences of P4P for psychiatry. Only this critical reflection can help
psychiatry to keep its identity as a humane service for suffering people.
PMID- 26429197
TI - Intra-prosthetic dislocation of dual-mobility cups after total hip arthroplasty:
potential causes from a clinical and biomechanical perspective.
AB - INTRODUCTION: Recurrent dislocation of total hip arthroplasty is a frequent
indication for revision surgery. Hip joint stability depends on implant design,
cup position and crucially on femoral head diameter. Due to an effective ultra
large diameter femoral head, dual-mobility cups are considered an attractive
solution to prevent dislocation in unstable conditions. Although patients
obviously benefit for many years in terms of mobility and pain, an increase of
intra-prosthetic dislocation reports using dual-mobility cups has been recently
observed. However, the failure mechanism of this implant-specific complication,
which is characterized by the loss of the positive-locking between the femoral
head and the mobile liner, is not yet completely understood. METHODS: A
comprehensive search was performed with the PubMed database and a search engine
to overview this topic and to identify potential causes for this implant-specific
failure from a clinical and biomechanical perspective. RESULTS: Peri-operative
findings indicate extensive fibrosis at the large articulation as well as cup
loosening as potential causes. In addition, current research has shown that the
failure mechanism is affected by the surface topography of the femoral neck and
in particular by the design of the mobile liner. DISCUSSION: In clinical practice
it is necessary to differentiate a classic dislocation between the mobile liner
and the metallic shell from an intra-prosthetic dislocation between the femoral
head and the liner. CONCLUSION: Due to the increasing popularity of dual-mobility
cups in total hip arthroplasty, the understanding of which implant-specific
features or tissue response may increase the risk of intra-prosthetic dislocation
is of major importance for reduced revision rates by using optimized surgical
techniques and implant designs.
PMID- 26429198
TI - Expression and Localization of Aquaporin 4 and Aquaporin 5 along the Large
Intestine of Colostrum-Suckling Buffalo Calves.
AB - Aquaporins (AQPs) are membrane channel proteins that play a role in regulating
water permeability in many tissues. To date, seven isoforms of AQPs have been
reported in the gastrointestinal tract in different mammalian species. In
contrast, both tissue distribution and expression of AQPs are unknown in the
buffalo. The purpose of this study was to investigate the expression of both AQP4
and AQP5 mRNAs and their relative proteins in the large intestinal tracts of
buffalo calves after colostrum suckling using reverse transcriptase polymerase
chain reaction (RT-PCR), Western blotting and immunohistochemistry. Our results
revealed a diversified tissue AQP4 and AQP5 immunolocalization accompanied by
their highest expression in the tissues of colostrum-suckling buffalo calves
confirmed by Western blotting. In particular, AQP4 was distributed along the
endothelium and enterocytes while AQP5 in the endocrine cells. These findings
provide direct evidence for AQP4 and AQP5 expression in the large intestine,
suggesting that different AQPs collaborate functionally and distinctively in
water handling during intestinal development, especially during the first period
after delivery.
PMID- 26429199
TI - Recognizing drug targets using evolutionary information: implications for
repurposing FDA-approved drugs against Mycobacterium tuberculosis H37Rv.
AB - Drug repurposing to explore target space has been gaining pace over the past
decade with the upsurge in the use of systematic approaches for computational
drug discovery. Such a cost and time-saving approach gains immense importance for
pathogens of special interest, such as Mycobacterium tuberculosis H37Rv. We
report a comprehensive approach to repurpose drugs, based on the exploration of
evolutionary relationships inferred from the comparative sequence and structural
analyses between targets of FDA-approved drugs and the proteins of M.
tuberculosis. This approach has facilitated the identification of several
polypharmacological drugs that could potentially target unexploited M.
tuberculosis proteins. A total of 130 FDA-approved drugs, originally intended
against other diseases, could be repurposed against 78 potential targets in M.
tuberculosis. Additionally, we have also made an attempt to augment the chemical
space by recognizing compounds structurally similar to FDA-approved drugs. For
three of the attractive cases we have investigated the probable binding modes of
the drugs in their corresponding M. tuberculosis targets by means of structural
modelling. Such prospective targets and small molecules could be prioritized for
experimental endeavours, and could significantly influence drug-discovery and
drug-development programmes for tuberculosis.
PMID- 26429202
TI - Gout and Association with Erectile Dysfunction.
PMID- 26429201
TI - Featured Article: Nuclear export of opioid growth factor receptor is CRM1
dependent.
AB - Opioid growth factor receptor (OGFr) facilitates growth inhibition in the
presence of its specific ligand opioid growth factor (OGF), chemically termed
[Met(5)]-enkephalin. The function of the OGF-OGFr axis requires the receptor to
translocate to the nucleus. However, the mechanism of nuclear export of OGFr is
unknown. In this study, endogenous OGFr, as well as exogenously expressed OGFr
EGFP, demonstrated significant nuclear accumulation in response to leptomycin B
(LMB), an inhibitor of CRM1-dependent nuclear export, suggesting that OGFr is
exported in a CRM1-dependent manner. One consensus sequence for a nuclear export
signal (NES) was identified. Mutation of the associated leucines, L217 L220 L223
and L225, to alanine resulted in decreased nuclear accumulation. NES-EGFP
responded to LMB, indicating that this sequence is capable of functioning as an
export signal in isolation. To determine why the sequence functions differently
in isolation than as a full length protein, the localization of subNES was
evaluated in the presence and absence of MG132, a potent inhibitor of proteosomal
degradation. MG132 had no effect of subNES localization. The role of tandem
repeats located at the C-terminus of OGFr was examined for their role in nuclear
trafficking. Six of seven tandem repeats were removed to form deltaTR. DeltaTR
localized exclusively to the nucleus indicating that the tandem repeats may
contribute to the localization of the receptor. Similar to the loss of cellular
proliferation activity (i.e. inhibition) recorded with subNES, deltaTR also
demonstrated a significant loss of inhibitory activity indicating that the
repeats may be integral to receptor function. These experiments reveal that OGFr
contains one functional NES, L217 L220 L223 and L225 and can be exported from the
nucleus in a CRM1-dependent manner.
PMID- 26429200
TI - MicroRNAs as biomarkers of hepatotoxicity in a randomized placebo-controlled
study of simvastatin and ubiquinol supplementation.
AB - Statins are potent cholesterol-lowering drugs and are generally well tolerated.
Hepatotoxicity is a rare but serious adverse effect of statins; however, its
mechanisms are not clear. Coenzyme Q10 deficiency has been suggested, and
supplementation of reduced coenzyme Q10 (ubiquinol) has been shown to have
hepatoprotective effects. MicroRNAs (miRNAs) are small nucleotides that have been
shown to be up-regulated in drug-induced liver injury. We hypothesized that
circulating miRNAs may be differentially regulated after simvastatin treatment
and by comparing with that of simvastatin and ubiquinol supplementation could
potentially uncover signatory miRNA profile for simvastatin-induced liver injury.
In this double-blind, prospective, randomized-controlled trial, miRNA profiles
and liver enzymes were compared between simvastatin-treated patients, with and
without ubiquinol supplementation, over 12 weeks compared to baseline. miRNA
expression was further validated in HepG2 liver cell lines by real-time PCR.
Changes in miR-192, miR-146a, miR-148a, miR-15a, and miR-21 were positively
correlated (p<0.05) with alanine aminotransferase in simvastatin-only treated
patients. In ubiquinol supplementation group, alanine aminotransferase and
alkaline phosphatase were significantly down-regulated after 12 weeks and changes
in miR-15a, miR-21 and miR-33a were negatively correlated with alkaline
phosphatase (p < 0.05). Bioinformatics analyses predicted that miRNA regulation
in simvastatin group was related to reduce proliferation and adenosine
triphosphate-binding cassette transporters. Ubiquinol supplementation
additionally regulated miRNAs that inhibit apoptotic and inflammatory pathways,
suggesting potential hepatoprotective effects. Our results suggest that 20 mg/day
of simvastatin does not have significant risk of hepatotoxicity and ubiquinol
supplementation may, at the miRNA level, provide potential beneficial changes to
reduce the effects of coenzyme Q10 deficiency in the liver.
PMID- 26429203
TI - The Renaissance of Antineutrophil Cytoplasmic Antibodies as a Predictor of
Relapse: Ippon for Japan.
PMID- 26429204
TI - Do "Evidence-Based Recommendations" Need to Reveal the Evidence? Minimal Criteria
Supporting an "Evidence Claim".
PMID- 26429205
TI - Dysphagia Related to Esophagus Compression by Anterior Cervical Ossification in a
Patient with Ankylosing Spondylitis.
PMID- 26429206
TI - Levamisole-induced Vasculitis in a Cocaine User.
PMID- 26429207
TI - Switching from Intravenous to Subcutaneous Formulation of Abatacept: Different
Results in a Series of 21 Patients.
PMID- 26429208
TI - Dr. Genovese comments.
PMID- 26429209
TI - Dr. Reggia, et al, reply.
PMID- 26429210
TI - 14-3-3eta in "Seronegative" Rheumatoid Arthritis.
PMID- 26429211
TI - Metallocorroles as Nonprecious-Metal Catalysts for Oxygen Reduction.
AB - The future of affordable fuel cells strongly relies on the design of earth
abundant (non-platinum) catalysts for the electrochemical oxygen reduction
reaction (ORR). However, the bottleneck in the overall process occurs therein. We
have examined herein trivalent Mn, Fe, Co, Ni, and Cu complexes of beta-pyrrole
brominated corrole as ORR catalysts. The adsorption of these complexes on a high
surface-area carbon powder (BP2000) created a unique composite material, used for
electrochemical measurements in acidic aqueous solutions. These experiments
disclosed a clear dependence of the catalytic activity on the metal center of the
complexes, in the order of Co>Fe>Ni>Mn>Cu. The best catalytic performance was
obtained for the Co(III) corrole, whose onset potential was as positive as 0.81 V
versus the reversible hydrogen electrode (RHE). Insight into the properties of
these systems was gained by spectroscopic and computational characterization of
the reduced and oxidized forms of the metallocorroles.
PMID- 26429212
TI - Regulation and innovation in healthcare.
PMID- 26429214
TI - Restrictive regulation constrains delivery of an integrated, collaborative and
responsive health sector.
PMID- 26429215
TI - Restrictive regulatory practice.
PMID- 26429216
TI - Motor neuron disease: current management and future prospects.
AB - Motor neuron disease (MND) is characterised by progressive neurological
deterioration and coexistence of upper and lower motor neuron signs. Over the
past decade, evidence has emerged of unique pathophysiological processes,
including glutamate-mediated excitotoxicity, which has resulted in the
development of novel diagnostic investigations and uncovered potential
therapeutic targets. Advances in genetics, including the recently discovered
C9orf72 gene, have radically changed the pathological mindset, from MND being
classified as a neuromuscular disease to one that MND forms a continuum with
other primary neurodegenerative disorders, including frontotemporal dementia. The
present review will highlight the improvements that have occurred in clinical
care, in conjunction with recent scientific developments.
PMID- 26429217
TI - Disseminated Mycobacterium haemophilum skeletal disease in a patient with
interferon-gamma deficiency.
AB - Disseminated non-tuberculous mycobacterial (NTM) infection is rare in
immunocompetent adults. Anti-interferon-gamma (IFN-gamma) autoantibodies have
recently been associated with NTM infections, particularly in patients of Asian
ethnicity. We describe a case of disseminated Mycobacterium haemophilum skeletal
infection due to anti IFN-gamma autoantibodies in a 71-year-old Cambodian man. He
responded to a combination of anti-mycobacterial antibiotics without requirement
for immunomodulator therapy. Testing for acquired IFN-gamma deficiency due to IFN
gamma autoantibodies should be considered when standard tests for
immunodeficiency are negative in patients with unusual or severe opportunistic
infections, including NTM.
PMID- 26429218
TI - Intravenous cyclophosphamide as a therapeutic option for severe refractory
gastric antral vascular ectasia in systemic sclerosis.
AB - Gastric antral vascular ectasia (GAVE) is a rare but important cause of upper
gastrointestinal bleeding. It is commonly associated with autoimmune conditions
such as systemic sclerosis, and standard treatment involves both supportive
measures, as well as endoscopic interventional therapies. While the current
therapies are effective for most patients, a few patients develop severe and
refractory bleeding. Herein we report two cases of refractory GAVE in patients
with diffuse scleroderma, which improved significantly after the administration
of intravenous cyclophosphamide. One of these cases is, to our knowledge, the
first reported case of cyclophosphamide being used specifically for the treatment
of refractory GAVE.
PMID- 26429219
TI - Compliance of males with stage 1 testicular germ cell tumours on an active
surveillance protocol.
AB - The aim of this retrospective study was to determine the rate of compliance among
57 males with stage 1 testicular germ cell tumours on an active surveillance
protocol at a single Australian centre. At median follow up of 24 months, 81% had
adequate compliance with the follow-up regimen, 12% were lost to follow up, and
16% relapsed; none between protocol visits. Active surveillance is an acceptable
alternative to adjuvant therapy for stage 1 testicular germ cell tumours, with
reduced toxicity for most and equivalent survival, but requires efforts to
maintain adequate compliance with follow up to avoid late detection of
recurrence.
PMID- 26429220
TI - Dangerous liaisons: doctors-in-training and the pharmaceutical industry.
AB - Interaction between doctors and the pharmaceutical industry is long-standing and
ingrained in modern practice. Doctors-in-training are at a vulnerable stage of
their careers, both in requiring knowledge and forming lasting relationships.
There is evidence that limiting contact between industry and junior doctors has a
positive effect on subsequent clinical behaviour. Currently in Australia, there
is no limitation on pharmaceutical representatives approaching doctors-in
training, and the majority of education sessions are sponsored by pharmaceutical
companies. This purposefully creates a sense of reciprocity, which may have
adverse long-term consequences on attitudes, behaviours and patient care. Several
guidelines exist that may assist junior doctors in navigating these potential
interactions, most notably the Royal Australasian College of Physicians' own
Guidelines for Ethical Relationships between Physicians and Industry. Despite
this, there is no reflection of its importance or necessity within subspecialty
curricula. This should be rectified, to the benefit of both the profession and
public.
PMID- 26429221
TI - Hypertrophic osteoarthropathy with imatinib therapy.
PMID- 26429222
TI - Two cases of spondylodiscitis caused by Parvimonas micra.
PMID- 26429223
TI - Systemic Bacillus Calmette-Guerin sepsis manifesting as hypercalcaemia and
thrombocytopenia as a complication of intravesical Bacillus Calmette-Guerin
therapy.
PMID- 26429224
TI - Angiotensin-converting enzyme inhibitor-induced angioedema and icatibant: a new
hope.
PMID- 26429225
TI - Generic substitution in contravention of doctor's prescriptions.
PMID- 26429226
TI - Author reply.
PMID- 26429227
TI - Conflict of interest statements: clarification.
PMID- 26429229
TI - "I Was a Spectacle... A Freak Show at the Circus": A Transgender Person's ED
Experience and Implications for Nursing Practice.
PMID- 26429228
TI - Mechanisms Influencing Circadian Blood Pressure Patterns Among Individuals with
HIV.
AB - HIV+ individuals have an increased risk for cardiovascular disease (CVD), but the
mechanisms behind this association are poorly understood. While hypertension is a
well-established CVD risk factor, clinic-based blood pressure (BP) assessment by
itself cannot identify several important BP patterns, including white coat
hypertension, masked hypertension, nighttime hypertension, and nighttime BP
dipping. These BP patterns can be identified over a 24-h period by ambulatory BP
monitoring (ABPM). In this review, we provide an overview of the potential value
of conducting ABPM in HIV+ individuals. ABPM phenotypes associated with increased
CVD risk include masked hypertension (i.e., elevated out-of-clinic BP despite non
elevated clinic BP), nighttime hypertension, and a non-dipping BP pattern (i.e.,
a drop in BP of <10 % from daytime to nighttime). These adverse ABPM phenotypes
may be highly relevant in the setting of HIV infection, given that increased
levels of inflammatory biomarkers, high psychosocial burden, high prevalence of
sleep disturbance, and autonomic dysfunction have been commonly reported in HIV+
persons. Additionally, although antiretroviral therapy (ART) is associated with
lower AIDS-related morbidity and CVD risk, the mitochondrial toxicity, oxidative
stress, lipodystrophy, and insulin resistance associated with long-term ART use
potentially lead to adverse ABPM phenotypes. Existing data on ABPM phenotypes in
the setting of HIV are limited, but suggest an increased prevalence of a non
dipping BP pattern. In conclusion, identifying ABPM phenotypes may provide
crucial information regarding the mechanisms underlying the excess CVD risk in
HIV+ individuals.
PMID- 26429230
TI - Nanoparticle conversion to biofilms: in vitro demonstration using serum-derived
mineralo-organic nanoparticles.
AB - AIMS: Mineralo-organic nanoparticles (NPs) detected in biological fluids have
been described as precursors of physiological and pathological calcifications in
the body. Our main objective was to examine the early stages of mineral NP
formation in body fluids. MATERIALS & METHODS: A nanomaterial approach based on
atomic force microscopy, dynamic light scattering, electron microscopy and
spectroscopy was used. RESULTS: The mineral particles, which contain the serum
proteins albumin and fetuin-A, initially precipitate in the form of round
amorphous NPs that gradually grow in size, aggregate and coalesce to form
crystalline mineral films similar to the structures observed in calcified human
arteries. CONCLUSION: Our study reveals the early stages of particle formation
and provides a platform to analyze the role(s) of mineralo-organic NPs in human
tissues.
PMID- 26429231
TI - Is compliance with hospital accreditation associated with length of stay and
acute readmission? A Danish nationwide population-based study.
AB - OBJECTIVE: To examine the association between compliance with hospital
accreditation and length of stay (LOS) and acute readmission (AR). DESIGN: A
nationwide population-based follow-up study from November 2009 to December 2012.
SETTING: Public, non-psychiatric Danish hospitals. PARTICIPANTS: In-patients
admitted with one of 80 diagnoses. INTERVENTION: Accreditation by the first
version of The Danish Healthcare Quality Programme. Using an on-site survey,
surveyors assessed the level of compliance with the standards. The hospital was
awarded either fully (n = 11) or partially accredited (n = 20). MAIN OUTCOME
MEASURES: LOS including transfers between hospitals and all-cause AR within 30
days after discharge. The Cox Proportional Hazard regression was used to compute
hazard ratios (HRs) adjusted for potential confounding factors and cluster effect
at hospital level. RESULTS: For analyses of LOS, 275 589 in-patients were
included of whom 266 532 were discharged alive and included in the AR analyses.
The mean LOS was 4.51 days (95% confidence interval (CI): 4.46-4.57) at fully and
4.54 days (95% CI: 4.50-4.57) at partially accredited hospitals, respectively.
After adjusting for confounding factors, the adjusted HR for time to discharge
was 1.07 (95% CI: 1.01-1.14). AR within 30 days after discharge was 13.70% (95%
CI: 13.45-13.95) at fully and 12.72% (95% CI: 12.57-12.86) at partially
accredited hospitals, respectively, corresponding to an adjusted HR of 1.01 (95%
CI: 0.92-1.10). CONCLUSION: Admissions at fully accredited hospitals were
associated with a shorter LOS compared with admissions at partially accredited
hospitals, although the difference was modest. No difference was observed in AR
within 30 days after discharge.
PMID- 26429232
TI - Point/Counterpoint. Only a therapist should operate an HDR unit for patient
treatments.
PMID- 26429233
TI - Daily QA of linear accelerators using only EPID and OBI.
AB - PURPOSE: As treatment delivery becomes more complex, there is a pressing need for
robust quality assurance (QA) tools to improve efficiency and comprehensiveness
while simultaneously maintaining high accuracy and sensitivity. This work aims to
present the hardware and software tools developed for comprehensive QA of linear
accelerator (LINAC) using only electronic portal imaging devices (EPIDs) and kV
flat panel detectors. METHODS: A daily QA phantom, which includes two
orthogonally positioned phantoms for QA of MV-beams and kV onboard imaging (OBI)
is suspended from the gantry accessory holder to test both geometric and
dosimetric components of a LINAC and an OBI. The MV component consists of a 0.5
cm water-equivalent plastic sheet incorporating 11 circular steel plugs for
transmission measurements through multiple thicknesses and one resolution plug
for MV-image quality testing. The kV-phantom consists of a Leeds phantom (TOR-18
FG phantom supplied by Varian) for testing low and high contrast resolutions. In
the developed process, the existing LINAC tools were used to automate daily
acquisition of MV and kV images and software tools were developed for
simultaneous analysis of these images. A method was developed to derive and
evaluate traditional QA parameters from these images [output, flatness, symmetry,
uniformity, TPR20/10, and positional accuracy of the jaws and multileaf
collimators (MLCs)]. The EPID-based daily QA tools were validated by performing
measurements on a detuned 6 MV beam to test its effectiveness in detecting errors
in output, symmetry, energy, and MLC positions. The developed QA process was
clinically commissioned, implemented, and evaluated on a Varian TrueBeam LINAC
(Varian Medical System, Palo Alto, CA) over a period of three months. RESULTS:
Machine output constancy measured with an EPID (as compared against a calibrated
ion-chamber) is shown to be within +/-0.5%. Beam symmetry and flatness deviations
measured using an EPID and a 2D ion-chamber array agree within +/-0.5% and +/
1.2% for crossline and inline profiles, respectively. MLC position errors of 0.5
mm can be detected using a picket fence test. The field size and phantom
positioning accuracy can be determined within 0.5 mm. The entire daily QA process
takes ~15 min to perform tests for 5 photon beams, MLC tests, and imaging checks.
CONCLUSIONS: The exclusive use of EPID-based QA tools, including a QA phantom and
simultaneous analysis software tools, has been demonstrated as a viable,
efficient, and comprehensive process for daily evaluation of LINAC performance.
PMID- 26429234
TI - Technical Note: Synchrotron-based high-energy x-ray phase sensitive
microtomography for biomedical research.
AB - PURPOSE: Propagation-based phase-contrast CT (PPCT) utilizes highly sensitive
phase-contrast technology applied to x-ray microtomography. Performing phase
retrieval on the acquired angular projections can enhance image contrast and
enable quantitative imaging. In this work, the authors demonstrate the validity
and advantages of a novel technique for high-resolution PPCT by using the
generalized phase-attenuation duality (PAD) method of phase retrieval. METHODS: A
high-resolution angular projection data set of a fish head specimen was acquired
with a monochromatic 60-keV x-ray beam. In one approach, the projection data were
directly used for tomographic reconstruction. In two other approaches, the
projection data were preprocessed by phase retrieval based on either the
linearized PAD method or the generalized PAD method. The reconstructed images
from all three approaches were then compared in terms of tissue contrast-to-noise
ratio and spatial resolution. RESULTS: The authors' experimental results
demonstrated the validity of the PPCT technique based on the generalized PAD
based method. In addition, the results show that the authors' technique is
superior to the direct PPCT technique as well as the linearized PAD-based PPCT
technique in terms of their relative capabilities for tissue discrimination and
characterization. CONCLUSIONS: This novel PPCT technique demonstrates great
potential for biomedical imaging, especially for applications that require high
spatial resolution and limited radiation exposure.
PMID- 26429236
TI - Lung motion estimation using dynamic point shifting: An innovative model based on
a robust point matching algorithm.
AB - PURPOSE: Image-guided radiotherapy is an advanced 4D radiotherapy technique that
has been developed in recent years. However, respiratory motion causes
significant uncertainties in image-guided radiotherapy procedures. To address
these issues, an innovative lung motion estimation model based on a robust point
matching is proposed in this paper. METHODS: An innovative robust point matching
algorithm using dynamic point shifting is proposed to estimate patient-specific
lung motion during free breathing from 4D computed tomography data. The
correspondence of the landmark points is determined from the Euclidean distance
between the landmark points and the similarity between the local images that are
centered at points at the same time. To ensure that the points in the source
image correspond to the points in the target image during other phases, the
virtual target points are first created and shifted based on the similarity
between the local image centered at the source point and the local image centered
at the virtual target point. Second, the target points are shifted by the
constrained inverse function mapping the target points to the virtual target
points. The source point set and shifted target point set are used to estimate
the transformation function between the source image and target image. RESULTS:
The performances of the authors' method are evaluated on two publicly available
DIR-lab and POPI-model lung datasets. For computing target registration errors on
750 landmark points in six phases of the DIR-lab dataset and 37 landmark points
in ten phases of the POPI-model dataset, the mean and standard deviation by the
authors' method are 1.11 and 1.11 mm, but they are 2.33 and 2.32 mm without
considering image intensity, and 1.17 and 1.19 mm with sliding conditions. For
the two phases of maximum inhalation and maximum exhalation in the DIR-lab
dataset with 300 landmark points of each case, the mean and standard deviation of
target registration errors on the 3000 landmark points of ten cases by the
authors' method are 1.21 and 1.04 mm. In the EMPIRE10 lung registration
challenge, the authors' method ranks 24 of 39. According to the index of the
maximum shear stretch, the authors' method is also efficient to describe the
discontinuous motion at the lung boundaries. CONCLUSIONS: By establishing the
correspondence of the landmark points in the source phase and the other target
phases combining shape matching and image intensity matching together, the
mismatching issue in the robust point matching algorithm is adequately addressed.
The target registration errors are statistically reduced by shifting the virtual
target points and target points. The authors' method with consideration of
sliding conditions can effectively estimate the discontinuous motion, and the
estimated motion is natural. The primary limitation of the proposed method is
that the temporal constraints of the trajectories of voxels are not introduced
into the motion model. However, the proposed method provides satisfactory motion
information, which results in precise tumor coverage by the radiation dose during
radiotherapy.
PMID- 26429235
TI - Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study.
AB - PURPOSE: Delivery of sufficient amounts of therapeutic drugs into the eye for
treatment of various ocular diseases is often a challenging task. Ultrasound was
shown to be effective in enhancing ocular drug delivery in the authors' previous
in vitro and in vivo studies. METHODS: The study reported here was designed to
investigate the safety of ultrasound application and its potential thermal
effects in the eye using PZFlex modeling software. The safety limit in this study
was set as a temperature increase of no more than 1.5 degrees C based on
regulatory recommendations and previous experimental safety studies. Acoustic and
thermal specifications of different human eye tissues were obtained from the
published literature. The tissues of particular interest in this modeling safety
study were cornea, lens, and the location of optic nerve in the posterior eye.
Ultrasound application was modeled at frequencies of 400 kHz-1 MHz, intensities
of 0.3-1 W/cm(2), and exposure duration of 5 min, which were the parameters used
in the authors' previous drug delivery experiments. The baseline eye temperature
was 37 degrees C. RESULTS: The authors' results showed that the maximal tissue
temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40
degrees C in the cornea, 39.5, 40, 42, and 43 degrees C in the center of the
lens, and 37.5, 38.5, and 39 degrees C in the back of the eye (at the optic
nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively.
CONCLUSIONS: The ocular temperatures reached at higher frequencies were
considered unsafe based on current recommendations. At a frequency of 400 kHz and
intensity of 0.8 W/cm(2) (parameters shown in the authors' previous in vivo
studies to be optimal for ocular drug delivery), the temperature increase was
small enough to be considered safe inside different ocular tissues. However, the
impact of orbital bone and tissue perfusion should be included in future modeling
efforts to determine the safety of this method in the whole orbit especially
regarding potential adverse optic nerve heating at the location of the bone.
PMID- 26429237
TI - Angular dependence of dose sensitivity of nanoDot optically stimulated
luminescent dosimeters in different radiation geometries.
AB - PURPOSE: A type of in vivo dosimeter, an optically stimulated luminescent
dosimeter, OSLD, may have dose sensitivity that depends on the angle of incidence
of radiation. This work measures how angular dependence of a nanoDot changes with
the geometry of the phantom in which irradiation occurs and with the intrinsic
structure of the nanoDot. METHODS: The OSLDs used in this work were nanoDot
dosimeters (Landauer, Inc., Glenwood, IL), which were read with a MicroStar
reader (Landauer, Inc., Glenwood, IL). Dose to the OSLDs was delivered by 6 MV x
rays. NanoDots with various intrinsic sensitivities were irradiated in numerous
phantoms that had geometric shapes of cylinders, rectangles, and a cube. RESULTS:
No angular dependence was seen in cylindrical phantoms, cubic phantoms, or
rectangular phantoms with a thickness to width ratio of 0.3 or 1.5. An angular
dependence of 1% was observed in rectangular phantoms with a thickness to width
of 0.433-0.633. A group of nanoDots had sensitive layers with mass density of
2.42-2.58 g/cm(3) and relative sensitivity of 0.92-1.09 and no difference in
their angular dependence. Within experimental uncertainty, nanoDot measurements
agree with a parallel-plate ion chamber at a depth of maximum dose. CONCLUSIONS:
When irradiated in cylindrical, rectangular, and cubic phantoms, nanoDots show a
maximum angular dependence of 1% or less at an incidence angle of 90 degrees .
For a sample of 78 new nanoDots, the range of their relative intrinsic
sensitivity is 0.92-1.09. For a sample of ten nanoDots, on average, the mass in
the sensitive layer is 73.1% Al2O3:C and 26.9% polyester. The mass density of the
sensitive layer of a nanoDot disc is between 2.42 and 2.58 g/cm(3). The angular
dependence is not related to Al2O3:C loading of the nanoDot disc. The nanoDot at
the depth of maximum dose has no more angular dependence than a parallel-plate
ion chamber.
PMID- 26429238
TI - Automatic detection of large pulmonary solid nodules in thoracic CT images.
AB - PURPOSE: Current computer-aided detection (CAD) systems for pulmonary nodules in
computed tomography (CT) scans have a good performance for relatively small
nodules, but often fail to detect the much rarer larger nodules, which are more
likely to be cancerous. We present a novel CAD system specifically designed to
detect solid nodules larger than 10 mm. METHODS: The proposed detection pipeline
is initiated by a three-dimensional lung segmentation algorithm optimized to
include large nodules attached to the pleural wall via morphological processing.
An additional preprocessing is used to mask out structures outside the pleural
space to ensure that pleural and parenchymal nodules have a similar appearance.
Next, nodule candidates are obtained via a multistage process of thresholding and
morphological operations, to detect both larger and smaller candidates. After
segmenting each candidate, a set of 24 features based on intensity, shape,
blobness, and spatial context are computed. A radial basis support vector machine
(SVM) classifier was used to classify nodule candidates, and performance was
evaluated using ten-fold cross-validation on the full publicly available lung
image database consortium database. RESULTS: The proposed CAD system reaches a
sensitivity of 98.3% (234/238) and 94.1% (224/238) large nodules at an average of
4.0 and 1.0 false positives/scan, respectively. CONCLUSIONS: The authors conclude
that the proposed dedicated CAD system for large pulmonary nodules can identify
the vast majority of highly suspicious lesions in thoracic CT scans with a small
number of false positives.
PMID- 26429239
TI - Quantitative early decision making metric for identifying irregular breathing in
4DCT.
AB - PURPOSE: To develop a quantitative early decision making metric for prediction of
breathing pattern and irregular breathing and validate the metric in a large
patient population receiving clinical phase-sorted four-dimensional computed
tomography (4DCT). METHODS: This study employed three patient cohorts. The first
cohort contained 47 patients, imaged with a nonclinical tidal volume metric. The
second cohort contained a sample of 256 patients who received a clinical 4DCT.
The third cohort contained 86 patients who received three 4DCT scans at 1-week
increment during the course of radiotherapy. The second and third cohorts did not
have tidal volume measurements, as per standard radiation oncology clinical
practice. Based on a previously published technique that used a single abdominal
surrogate, the ratio of extreme inhalation tidal volume to normal inhalation
tidal volume (kappa) metric was calculated and the patient breathing pattern was
characterized. The use of a single surrogate precluded the use of a kappa
determined by tidal volume, so a kappa(rel) was defined based on the amplitude of
the surrogate. Patients were classified as either Type 1 or Type 2, based on a
previously published technique, where Type 1 patients were apneic at end of
exhalation and Type 2 patients exhibited forced respiration. The Ansari-Bradley
test was used to determine the statistical similarity between the Type 1 and Type
2 distributions. A Kruskal-Wallis one way analysis of variance was used to
determine the statistical similarities among the classified breathing types,
kappa(rel), and the qualified medical physicist denoted breathing classification
(regular or irregular). Receiver operator characteristic curves were used to
quantitatively determine optimal cutoff value j(kappa) and efficiency cutoff
value (tau(kappa)) kappa(rel) to provide a quantitative early warning of
irregular breathing during 4DCT procedures. RESULTS: The statistical tests show a
significant consistency for the breathing pattern classifications between the
physiologically measured cohort #1 and the remaining cohorts. The classification
types were statistically different between Type 1 and Type 2 patients over all
cohorts. Values of kappa(rel) in excess of 1.72 indicated a substantial presence
of irregular breathing that could negatively affect the quality of a 4DCT image
dataset. Values of kappa(rel) in lower than 1.45 indicated minimal presence of
irregular breathing. For values of kappa(rel) such that j(kappa) <= kappa(rel) <=
tau(kappa), the decision to reacquire the 4DCT would be at the discretion of the
physician. This accounted for only 11.9% of the patients in this study. The
magnitude of kappa(rel) held consistent over three weeks of treatment for 73% of
the patients in cohort #3. CONCLUSIONS: The decision making metric based on kappa
was shown to be an accurate classifier of regular and irregular breathing
patterns in a large patient population. Breathing type, as defined in a previous
published work, was accurately classified by kappa(rel) with the use of a single
respiratory surrogate compared to the physiological use of multiple respiratory
surrogates. This work provided a quantitative early decision making metric to
quickly and accurately assess breathing patterns as well as the presence and
magnitude of irregular breathing during 4DCT.
PMID- 26429240
TI - Measurement with microscopic MRI and simulation of flow in different aneurysm
models.
AB - PURPOSE: The impact and the development of aneurysms depend to a significant
degree on the exchange of liquid between the regular vessel and the pathological
extension. A better understanding of this process will lead to improved
prediction capabilities. The aim of the current study was to investigate fluid
exchange in aneurysm models of different complexities by combining microscopic
magnetic resonance measurements with numerical simulations. In order to evaluate
the accuracy and applicability of these methods, the fluid-exchange process
between the unaltered vessel lumen and the aneurysm phantoms was analyzed
quantitatively using high spatial resolution. METHODS: Magnetic resonance flow
imaging was used to visualize fluid-exchange in two different models produced
with a 3D printer. One model of an aneurysm was based on histological findings.
The flow distribution in the different models was measured on a microscopic scale
using time of flight magnetic resonance imaging. The whole experiment was
simulated using fast graphics processing unit-based numerical simulations. The
obtained simulation results were compared qualitatively and quantitatively with
the magnetic resonance imaging measurements, taking into account flow and spin
lattice relaxation. RESULTS: The results of both presented methods compared well
for the used aneurysm models and the chosen flow distributions. The results from
the fluid-exchange analysis showed comparable characteristics concerning
measurement and simulation. Similar symmetry behavior was observed. Based on
these results, the amount of fluid-exchange was calculated. Depending on the
geometry of the models, 7% to 45% of the liquid was exchanged per second.
CONCLUSIONS: The result of the numerical simulations coincides well with the
experimentally determined velocity field. The rate of fluid-exchange between
vessel and aneurysm was well-predicted. Hence, the results obtained by simulation
could be validated by the experiment. The observed deviations can be caused by
the noise in the measurement and by the limited resolution of the simulation. The
resulting differences are small enough to allow reliable predictions of the flow
distribution in vessels with stents and for pulsed blood flow.
PMID- 26429242
TI - Monte Carlo reference data sets for imaging research: Executive summary of the
report of AAPM Research Committee Task Group 195.
AB - The use of Monte Carlo simulations in diagnostic medical imaging research is
widespread due to its flexibility and ability to estimate quantities that are
challenging to measure empirically. However, any new Monte Carlo simulation code
needs to be validated before it can be used reliably. The type and degree of
validation required depends on the goals of the research project, but, typically,
such validation involves either comparison of simulation results to physical
measurements or to previously published results obtained with established Monte
Carlo codes. The former is complicated due to nuances of experimental conditions
and uncertainty, while the latter is challenging due to typical graphical
presentation and lack of simulation details in previous publications. In
addition, entering the field of Monte Carlo simulations in general involves a
steep learning curve. It is not a simple task to learn how to program and
interpret a Monte Carlo simulation, even when using one of the publicly available
code packages. This Task Group report provides a common reference for
benchmarking Monte Carlo simulations across a range of Monte Carlo codes and
simulation scenarios. In the report, all simulation conditions are provided for
six different Monte Carlo simulation cases that involve common x-ray based
imaging research areas. The results obtained for the six cases using four
publicly available Monte Carlo software packages are included in tabular form. In
addition to a full description of all simulation conditions and results, a
discussion and comparison of results among the Monte Carlo packages and the
lessons learned during the compilation of these results are included. This
abridged version of the report includes only an introductory description of the
six cases and a brief example of the results of one of the cases. This work
provides an investigator the necessary information to benchmark his/her Monte
Carlo simulation software against the reference cases included here before
performing his/her own novel research. In addition, an investigator entering the
field of Monte Carlo simulations can use these descriptions and results as a self
teaching tool to ensure that he/she is able to perform a specific simulation
correctly. Finally, educators can assign these cases as learning projects as part
of course objectives or training programs.
PMID- 26429241
TI - Determinants of the reliability of ultrasound tomography sound speed estimates as
a surrogate for volumetric breast density.
AB - PURPOSE: High breast density, as measured by mammography, is associated with
increased breast cancer risk, but standard methods of assessment have limitations
including 2D representation of breast tissue, distortion due to breast
compression, and use of ionizing radiation. Ultrasound tomography (UST) is a
novel imaging method that averts these limitations and uses sound speed measures
rather than x-ray imaging to estimate breast density. The authors evaluated the
reproducibility of measures of speed of sound and changes in this parameter using
UST. METHODS: One experienced and five newly trained raters measured sound speed
in serial UST scans for 22 women (two scans per person) to assess inter-rater
reliability. Intrarater reliability was assessed for four raters. A random
effects model was used to calculate the percent variation in sound speed and
change in sound speed attributable to subject, scan, rater, and repeat reads. The
authors estimated the intraclass correlation coefficients (ICCs) for these
measures based on data from the authors' experienced rater. RESULTS: Median
(range) time between baseline and follow-up UST scans was five (1-13) months.
Contributions of factors to sound speed variance were differences between
subjects (86.0%), baseline versus follow-up scans (7.5%), inter-rater evaluations
(1.1%), and intrarater reproducibility (~0%). When evaluating change in sound
speed between scans, 2.7% and ~0% of variation were attributed to inter- and
intrarater variation, respectively. For the experienced rater's repeat reads,
agreement for sound speed was excellent (ICC = 93.4%) and for change in sound
speed substantial (ICC = 70.4%), indicating very good reproducibility of these
measures. CONCLUSIONS: UST provided highly reproducible sound speed measurements,
which reflect breast density, suggesting that UST has utility in sensitively
assessing change in density.
PMID- 26429243
TI - Correcting scan-to-scan response variability for a radiochromic film-based
reference dosimetry system.
AB - PURPOSE: In radiochromic film dosimetry systems, measurements are usually
obtained from film images acquired on a CCD-based flatbed scanner. The authors
investigated factors affecting scan-to-scan response variability leading to
increased dose measurement uncertainty. METHODS: The authors used flatbed
document scanners to repetitively scan EBT3 radiochromic films exposed to doses 0
1000 cGy, together with three neutral density filters and three blue optical
filters. Scanning was performed under two conditions: scanner lid closed and
scanner lid opened/closed between scans. The authors also placed a scanner in a
cold room at 9 degrees C and later in a room at 22 degrees C and scanned EBT3
films to explore temperature effects. Finally, the authors investigated the
effect of altering the distance between the film and the scanner's light source.
RESULTS: Using a measurement protocol to isolate the contribution of the CCD and
electronic circuitry of the scanners, the authors found that the standard
deviation of response measurements for the EBT3 film model was about 0.17% for
one scanner and 0.09% for the second. When the lid of the first scanner was
opened and closed between scans, the average scan-to-scan difference of responses
increased from 0.12% to 0.27%. Increasing the sample temperature during scanning
changed the RGB response values by about -0.17, -0.14, and -0.05%/ degrees C,
respectively. Reducing the film-to-light source distance increased the RBG
response values about 1.1, 1.3, and 1.4%/mm, respectively. The authors observed
that films and film samples were often not flat with some areas up to 8 mm away
from the scanner's glass window. CONCLUSIONS: In the absence of measures to deal
with the response irregularities, each factor the authors investigated could lead
to dose uncertainty >2%. Those factors related to the film-to-light source
distance could be particularly impactful since the authors observed many
instances where the curl of film samples had the potential to cause dose
uncertainty in excess of 5%. Two expedients will eliminate the uncertainties: a
transparent sheet (preferably glass) placed over the scanned film keeps the film
to-light source distance constant, and an EBT3 reference film included in all
scans provides correction factors for measured response values.
PMID- 26429244
TI - Three-dimensional reconstruction of a vascular network by dynamic tracking of
magnetite nanoparticles.
AB - PURPOSE: Visualization of small blood vessels feeding tumor sites provides
important information on the tumors and their microenvironment. This information
plays an important role in targeted drug therapies using magnetic gradients.
However, capabilities of current clinical imaging modalities may be insufficient
to resolve complex microvascular networks. The purpose of this study is to map
the vascular network, 3D, based on the magnetic susceptibility contrast. METHODS:
Magnetic particles induce an inhomogeneity in the MRI's magnetic field in an
order much larger than their real size. This is an approach to compensate the
spatial resolution insufficiency of a clinical MR scanner. Micron-sized
agglomerations of magnetite nanoparticles were injected in a 3D phantom vascular
network, and a fast multislice, multiacquisition MR sequence was applied to track
the agglomerations along their trajectories. The experiment was performed twice
for two different imaging planes: coronal and transversal. The susceptibility
artifact in the images indicated the presence and the position of the
agglomerations. The calculated positions through multiple images were assembled
to build up the 3D distribution of the vascular network. RESULTS: The calculated
points were compared with the centerline of the channels, extracted from the 3D
reference image, to determine the absolute measurement error. The mean error was
measured to be approximately half of the pixel's size. It was found that the
positioning error on the axis perpendicular to the imaging slice was nearly twice
as high as on the imaging plane axes due to the slice thickness. In order to
compensate for the lack of resolution on the perpendicular axis, the
reconstruction was performed using a combination of coronal and transversal data.
The combination of the coordinates led to a significant decrease in the mean
measurement error at each segment in the vascular network (p < 0.001).
CONCLUSIONS: A method for 3D reconstruction of a microvascular network based on
the susceptibility contrast in MRI and using a clinical scanner and a commercial
receiver coil was proposed. The method presents a novel approach for
reconstruction of vascular networks using the susceptibility effect. The proposed
method may be applied to resolve vascular networks at a micrometric scale.
PMID- 26429245
TI - Monte Carlo simulations of the dose from imaging with GE eXplore 120 micro-CT
using GATE.
AB - PURPOSE: Small animals are increasingly used as translational models in
preclinical imaging studies involving microCT, during which the subjects can be
exposed to large amounts of radiation. While the radiation levels are generally
sublethal, studies have shown that low-level radiation can change physiological
parameters in mice. In order to rule out any influence of radiation on the
outcome of such experiments, or resulting deterministic effects in the subjects,
the levels of radiation involved need to be addressed. The aim of this study was
to investigate the radiation dose delivered by the GE eXplore 120 microCT non
invasively using Monte Carlo simulations in GATE and to compare results to
previously obtained experimental values. METHODS: Tungsten X-ray spectra were
simulated at 70, 80, and 97 kVp using an analytical tool and their half-value
layers were simulated for spectra validation against experimentally measured
values of the physical X-ray tube. A Monte Carlo model of the microCT system was
set up and four protocols that are regularly applied to live animal scanning were
implemented. The computed tomography dose index (CTDI) inside a PMMA phantom was
derived and multiple field of view acquisitions were simulated using the PMMA
phantom, a representative mouse and rat. RESULTS: Simulated half-value layers
agreed with experimentally obtained results within a 7% error window. The CTDI
ranged from 20 to 56 mGy and closely matched experimental values. Derived organ
doses in mice reached 459 mGy in bones and up to 200 mGy in soft tissue organs
using the highest energy protocol. Dose levels in rats were lower due to the
increased mass of the animal compared to mice. The uncertainty of all dose
simulations was below 14%. CONCLUSIONS: Monte Carlo simulations proved a valuable
tool to investigate the 3D dose distribution in animals from microCT. Small
animals, especially mice (due to their small volume), receive large amounts of
radiation from the GE eXplore 120 microCT, which might alter physiological
parameters in a longitudinal study setup.
PMID- 26429246
TI - SPEQTACLE: An automated generalized fuzzy C-means algorithm for tumor delineation
in PET.
AB - PURPOSE: Accurate tumor delineation in positron emission tomography (PET) images
is crucial in oncology. Although recent methods achieved good results, there is
still room for improvement regarding tumors with complex shapes, low signal-to
noise ratio, and high levels of uptake heterogeneity. METHODS: The authors
developed and evaluated an original clustering-based method called spatial
positron emission quantification of tumor-Automatic Lp-norm estimation
(SPEQTACLE), based on the fuzzy C-means (FCM) algorithm with a generalization
exploiting a Hilbertian norm to more accurately account for the fuzzy and non
Gaussian distributions of PET images. An automatic and reproducible estimation
scheme of the norm on an image-by-image basis was developed. Robustness was
assessed by studying the consistency of results obtained on multiple acquisitions
of the NEMA phantom on three different scanners with varying acquisition
parameters. Accuracy was evaluated using classification errors (CEs) on simulated
and clinical images. SPEQTACLE was compared to another FCM implementation, fuzzy
local information C-means (FLICM) and fuzzy locally adaptive Bayesian (FLAB).
RESULTS: SPEQTACLE demonstrated a level of robustness similar to FLAB
(variability of 14% +/- 9% vs 14% +/- 7%, p = 0.15) and higher than FLICM (45% +/
18%, p < 0.0001), and improved accuracy with lower CE (14% +/- 11%) over both
FLICM (29% +/- 29%) and FLAB (22% +/- 20%) on simulated images. Improvement was
significant for the more challenging cases with CE of 17% +/- 11% for SPEQTACLE
vs 28% +/- 22% for FLAB (p = 0.009) and 40% +/- 35% for FLICM (p < 0.0001). For
the clinical cases, SPEQTACLE outperformed FLAB and FLICM (15% +/- 6% vs 37% +/-
14% and 30% +/- 17%, p < 0.004). CONCLUSIONS: SPEQTACLE benefitted from the fully
automatic estimation of the norm on a case-by-case basis. This promising approach
will be extended to multimodal images and multiclass estimation in future
developments.
PMID- 26429247
TI - Theoretical detection threshold of the proton-acoustic range verification
technique.
AB - PURPOSE: Range verification in proton therapy using the proton-acoustic signal
induced in the Bragg peak was investigated for typical clinical scenarios. The
signal generation and detection processes were simulated in order to determine
the signal-to-noise limits. METHODS: An analytical model was used to calculate
the dose distribution and local pressure rise (per proton) for beams of different
energy (100 and 160 MeV) and spot widths (1, 5, and 10 mm) in a water phantom. In
this method, the acoustic waves propagating from the Bragg peak were generated by
the general 3D pressure wave equation implemented using a finite element method.
Various beam pulse widths (0.1-10 MUs) were simulated by convolving the acoustic
waves with Gaussian kernels. A realistic PZT ultrasound transducer (5 cm
diameter) was simulated with a Butterworth bandpass filter with consideration of
random noise based on a model of thermal noise in the transducer. The signal-to
noise ratio on a per-proton basis was calculated, determining the minimum number
of protons required to generate a detectable pulse. The maximum spatial
resolution of the proton-acoustic imaging modality was also estimated from the
signal spectrum. RESULTS: The calculated noise in the transducer was 12-28 mPa,
depending on the transducer central frequency (70-380 kHz). The minimum number of
protons detectable by the technique was on the order of 3-30 * 10(6) per pulse,
with 30-800 mGy dose per pulse at the Bragg peak. Wider pulses produced signal
with lower acoustic frequencies, with 10 MUs pulses producing signals with
frequency less than 100 kHz. CONCLUSIONS: The proton-acoustic process was
simulated using a realistic model and the minimal detection limit was established
for proton-acoustic range validation. These limits correspond to a best case
scenario with a single large detector with no losses and detector thermal noise
as the sensitivity limiting factor. Our study indicated practical proton-acoustic
range verification may be feasible with approximately 5 * 10(6) protons/pulse and
beam current.
PMID- 26429248
TI - Monte Carlo modeling of ultrasound probes for image guided radiotherapy.
AB - PURPOSE: To build Monte Carlo (MC) models of two ultrasound (US) probes and to
quantify the effect of beam attenuation due to the US probes for radiation
therapy delivered under real-time US image guidance. METHODS: MC models of two
Philips US probes, an X6-1 matrix-array transducer and a C5-2 curved-array
transducer, were built based on their megavoltage (MV) CT images acquired in a
Tomotherapy machine with a 3.5 MV beam in the EGSnrc, BEAMnrc, and DOSXYZnrc
codes. Mass densities in the probes were assigned based on an electron density
calibration phantom consisting of cylinders with mass densities between 0.2 and
8.0 g/cm(3). Beam attenuation due to the US probes in horizontal (for both
probes) and vertical (for the X6-1 probe) orientation was measured in a solid
water phantom for 6 and 15 MV (15 * 15) cm(2) beams with a 2D ionization chamber
array and radiographic films at 5 cm depth. The MC models of the US probes were
validated by comparison of the measured dose distributions and dose distributions
predicted by MC. Attenuation of depth dose in the (15 * 15) cm(2) beams and small
circular beams due to the presence of the probes was assessed by means of MC
simulations. RESULTS: The 3.5 MV CT number to mass density calibration curve was
found to be linear with R(2) > 0.99. The maximum mass densities in the X6-1 and
C5-2 probes were found to be 4.8 and 5.2 g/cm(3), respectively. Dose profile
differences between MC simulations and measurements of less than 3% for US probes
in horizontal orientation were found, with the exception of the penumbra region.
The largest 6% dose difference was observed in dose profiles of the X6-1 probe
placed in vertical orientation, which was attributed to inadequate modeling of
the probe cable. Gamma analysis of the simulated and measured doses showed that
over 96% of measurement points passed the 3%/3 mm criteria for both probes placed
in horizontal orientation and for the X6-1 probe in vertical orientation. The X6
1 probe in vertical orientation caused the highest attenuation of the 6 and 15 MV
beams, which at 10 cm depth accounted for 33% and 43% decrease compared to the
respective (15 * 15) cm(2) open fields. The C5-2 probe in horizontal orientation,
on the other hand, caused a dose increase of 10% and 53% for the 6 and 15 MV
beams, respectively, in the buildup region at 0.5 cm depth. For the X6-1 probe in
vertical orientation, the dose at 5 cm depth for the 3-cm diameter 6 MV and 5-cm
diameter 15 MV beams was attenuated compared to the corresponding open fields to
a greater degree by 65% and 43%, respectively. CONCLUSIONS: MC models of two US
probes used for real-time image guidance during radiotherapy have been built. Due
to the high beam attenuation of the US probes, the authors generally recommend
avoiding delivery of treatment beams that intersect the probe. However, the
presented MC models can be effectively integrated into US-guided radiotherapy
treatment planning in cases for which beam avoidance is not practical due to
anatomy geometry.
PMID- 26429249
TI - An iterative reduced field-of-view reconstruction for periodically rotated
overlapping parallel lines with enhanced reconstruction (PROPELLER) MRI.
AB - PURPOSE: To propose a new reduced field-of-view (rFOV) strategy for iterative
reconstructions in a clinical environment. Iterative reconstructions can
incorporate regularization terms to improve the image quality of periodically
rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) MRI.
However, the large amount of calculations required for full FOV iterative
reconstructions has posed a huge computational challenge for clinical usage. By
subdividing the entire problem into smaller rFOVs, the iterative reconstruction
can be accelerated on a desktop with a single graphic processing unit (GPU).
METHODS: This rFOV strategy divides the iterative reconstruction into blocks,
based on the block-diagonal dominant structure. A near real-time reconstruction
system was developed for the clinical MR unit, and parallel computing was
implemented using the object-oriented model. In addition, the Toeplitz method was
implemented on the GPU to reduce the time required for full interpolation. Using
the data acquired from the PROPELLER MRI, the reconstructed images were then
saved in the digital imaging and communications in medicine format. RESULTS: The
proposed rFOV reconstruction reduced the gridding time by 97%, as the total
iteration time was 3 s even with multiple processes running. A phantom study
showed that the structure similarity index for rFOV reconstruction was
statistically superior to conventional density compensation (p < 0.001). In vivo
study validated the increased signal-to-noise ratio, which is over four times
higher than with density compensation. Image sharpness index was improved using
the regularized reconstruction implemented. CONCLUSIONS: The rFOV strategy
permits near real-time iterative reconstruction to improve the image quality of
PROPELLER images. Substantial improvements in image quality metrics were
validated in the experiments. The concept of rFOV reconstruction may potentially
be applied to other kinds of iterative reconstructions for shortened
reconstruction duration.
PMID- 26429250
TI - Technical Note: Influence of Compton currents on profile measurements in small
volume ion chambers.
AB - PURPOSE: This work is to evaluate the effects of Compton current generation in
three small-volume ionization chambers on measured beam characteristics for
electron fields. METHODS: Beam scans were performed using Exradin A16, A26, and
PTW 31014 microchambers. Scans with varying chamber components shielded were
performed. Static point measurements, output factors, and cable only irradiations
were performed to determine the contribution of Compton currents to various
components of the chamber. Monte Carlo simulations were performed to evaluate why
one microchamber showed a significant reduction in Compton current generation.
RESULTS: Beam profiles demonstrated significant distortion for two of the three
chambers when scanned parallel to the chamber axis, produced by electron
deposition within the wire. Measurements of ionization produced within the cable
identified Compton current generation as the cause of these distortions. The size
of the central collecting wire was found to have the greatest influence on the
magnitude of Compton current generation. CONCLUSIONS: Microchambers can
demonstrate significant (>5%) deviations from properties as measured with larger
volume chambers (0.125 cm(3) and above). These deviations can be substantially
reduced by averaging measurements conducted at opposite polarities.
PMID- 26429251
TI - Evaluation of in vivo quantification accuracy of the Ingenuity-TF PET/MR.
AB - PURPOSE: The quantitative accuracy of standardized uptake values (SUVs) and
tracer kinetic uptake parameters in patient investigations strongly depends on
accurate determination of regional activity concentrations in positron emission
tomography (PET) data. This determination rests on the assumption that the given
scanner calibration is valid in vivo. In a previous study, we introduced a method
to test this assumption. This method allows to identify discrepancies in
quantitative accuracy in vivo by comparison of activity concentrations of urine
samples measured in a well-counter with activity concentrations extracted from
PET images of the bladder. In the present study, we have applied this method to
the Philips Ingenuity-TF PET/MR since at the present stage, absolute quantitative
accuracy of combined PET/MR systems is still under investigation. METHODS: Twenty
one clinical whole-body F18-FDG scans were included in this study. The bladder
region was imaged as the last bed position and urine samples were collected
afterward. PET images were reconstructed including MR-based attenuation
correction with and without truncation compensation and 3D regions-of-interest
(ROIs) of the bladder were delineated by three observers. To exclude partial
volume effects, ROIs were concentrically shrunk by 8-10 mm. Then, activity
concentrations were determined in the PET images for the bladder and for the
urine by measuring the samples in a calibrated well-counter. In addition,
linearity measurements of SUV vs singles rate and measurements of the stability
of the coincidence rate of "true" events of the PET/MR system were performed over
a period of 4 months. RESULTS: The measured in vivo activity concentrations were
significantly lower in PET/MR than in the well-counter with a ratio of the former
to the latter of 0.756 +/- 0.060 (mean +/- std. dev.), a range of 0.604-0.858,
and a P value of 3.9 ? 10(-14). While the stability measurements of the
coincidence rate of "true" events showed no relevant deviation over time, the
linearity scans revealed a systematic error of 8%-11% (avg. 9%) for the range of
singles rates present in the bladder scans. After correcting for this systematic
bias caused by shortcomings of the manufacturers calibration procedure, the PET
to well-counter ratio increased to 0.832 +/- 0.064 (0.668 -0.941), P = 1.1 ? 10(
10). After compensating for truncation of the upper extremities in the MR-based
attenuation maps, the ratio further improved to 0.871 +/- 0.069 (0.693-0.992), P
= 3.9 ? 10(-8). CONCLUSIONS: Our results show that the Philips PET/MR
underestimates activity concentrations in the bladder by 17%, which is 7
percentage points (pp.) larger than in the previously investigated PET and PET/CT
systems. We attribute this increased underestimation to remaining limitations of
the MR-based attenuation correction. Our results suggest that only a 2 pp. larger
underestimation of activity concentrations compared to PET/CT can be observed if
compensation of attenuation truncation of the upper extremities is applied. Thus,
quantification accuracy of the Philips Ingenuity-TF PET/MR can be considered
acceptable for clinical purposes given the +/-10% error margin in the EANM
guidelines. The comparison of PET images from the bladder region with urine
samples has proven a useful method. It might be interesting for evaluation and
comparison of the in vivo quantitative accuracy of PET, PET/CT, and especially
PET/MR systems from different manufacturers or in multicenter trials.
PMID- 26429252
TI - Technical Note: Initial characterization of the new EBT-XD Gafchromic film.
AB - PURPOSE: To assess the dosimetric accuracy and energy dependence of the new EBT
eXtended Dose (XD) Gafchromic film and to compare the lateral response artifact
(LRA) between EBT-XD and EBT3 film. METHODS: EBT3 and EBT-XD calibration curves
were created by exposing films to known doses from 0 to 3000 cGy using a 6 MV
beam. To assess the accuracy and dynamic range of EBT-XD, a 60 degrees enhanced
dynamic wedge (EDW) was used to deliver a dose range of approximately 200-2900
cGy. Comparison to treatment planning system (TPS) calculation was made using a
gamma analysis with 2%/2 mm passing criteria. To assess and compare the LRA
between EBT3 and EBT-XD, 21 * 21 cm(2) open fields delivered doses of 1000, 2000,
and 3000 cGy to both types of film. Films were placed at the center of the
scanner, and ratios of measured to TPS predicted doses were calculated at 50 and
80 mm lateral from the scanner center in order to quantitatively assess the LRA.
To evaluate the energy dependence of EBT-XD film, seven known doses ranging from
400 to 3000 cGy were delivered using both 6 and 18 MV beams and the resulting
optical densities (ODs) compared. RESULTS: The gamma passing rate was 99.1% for
the 6 MV EDW delivery. EBT-XD film exhibited minimal LRA (<1%) up to 3000 cGy. In
contrast, EBT3 demonstrated an under-response of 11.3% and 22.7% at lateral
positions of 50 and 80 mm, respectively, for the 3000 cGy exposure. Differences
between ODs of the EBT-XD films exposed to known doses from 6 to 18 MV beams were
<0.8% suggesting minimal energy dependence throughout this energy range.
CONCLUSIONS: The LRA of EBT-XD is greatly reduced when compared to EBT3. This in
combination with its accuracy from 0 to 3000 cGy and minimal energy dependence
from 6 to 18 MV makes EBT-XD film well suited for dosimetric measurements in high
dose SRS/SBRT applications.
PMID- 26429253
TI - Geometric validation of self-gating k-space-sorted 4D-MRI vs 4D-CT using a
respiratory motion phantom.
AB - PURPOSE: MRI is increasingly being used for radiotherapy planning, simulation,
and in-treatment-room motion monitoring. To provide more detailed temporal and
spatial MR data for these tasks, we have recently developed a novel self-gated
(SG) MRI technique with advantage of k-space phase sorting, high isotropic
spatial resolution, and high temporal resolution. The current work describes the
validation of this 4D-MRI technique using a MRI- and CT-compatible respiratory
motion phantom and comparison to 4D-CT. METHODS: The 4D-MRI sequence is based on
a spoiled gradient echo-based 3D projection reconstruction sequence with self
gating for 4D-MRI at 3 T. Respiratory phase is resolved by using SG k-space lines
as the motion surrogate. 4D-MRI images are reconstructed into ten temporal bins
with spatial resolution 1.56 * 1.56 * 1.56 mm(3). A MRI-CT compatible phantom was
designed to validate the performance of the 4D-MRI sequence and 4D-CT imaging. A
spherical target (diameter 23 mm, volume 6.37 ml) filled with high-concentration
gadolinium (Gd) gel is embedded into a plastic box (35 * 40 * 63 mm(3)) and
stabilized with low-concentration Gd gel. The phantom, driven by an air pump, is
able to produce human-type breathing patterns between 4 and 30 respiratory
cycles/min. 4D-CT of the phantom has been acquired in cine mode, and
reconstructed into ten phases with slice thickness 1.25 mm. The 4D images sets
were imported into a treatment planning software for target contouring. The
geometrical accuracy of the 4D MRI and CT images has been quantified using target
volume, flattening, and eccentricity. The target motion was measured by tracking
the centroids of the spheres in each individual phase. Motion ground-truth was
obtained from input signals and real-time video recordings. RESULTS: The dynamic
phantom has been operated in four respiratory rate (RR) settings, 6, 10, 15, and
20/min, and was scanned with 4D-MRI and 4D-CT. 4D-CT images have target
stretching, partial-missing, and other motion artifacts in various phases,
whereas the 4D-MRI images are visually free of those artifacts. Volume percentage
difference for the 6.37 ml target ranged from 5.3% +/- 4.3% to 10.3% +/- 5.9% for
4D-CT, and 1.47 +/- 0.52 to 2.12 +/- 1.60 for 4D-MRI. With an increase of
respiratory rate, the target volumetric and geometric deviations increase for 4D
CT images while remaining stable for the 4D-MRI images. Target motion amplitude
errors at different RRs were measured with a range of 0.66-1.25 mm for 4D-CT and
0.2-0.42 mm for 4D-MRI. The results of Mann-Whitney tests indicated that 4D-MRI
significantly outperforms 4D-CT in phase-based target volumetric (p = 0.027) and
geometric (p < 0.001) measures. Both modalities achieve equivalent accuracy in
measuring motion amplitude (p = 0.828). CONCLUSIONS: The k-space self-gated 4D
MRI technique provides a robust method for accurately imaging phase-based target
motion and geometry. Compared to 4D-CT, the current 4D-MRI technique demonstrates
superior spatiotemporal resolution, and robust resistance to motion artifacts
caused by fast target motion and irregular breathing patterns. The technique can
be used extensively in abdominal targeting, motion gating, and toward
implementing MRI-based adaptive radiotherapy.
PMID- 26429254
TI - Multidimensional dosimetry of 106Ru eye plaques using EBT3 films and its impact
on treatment planning.
AB - PURPOSE: The purpose of this study was to establish a method to perform
multidimensional radiochromic film measurements of (106)Ru plaques and to
benchmark the resulting dose distributions against Monte Carlo simulations (MC),
microdiamond, and diode measurements. METHODS: Absolute dose rates and relative
dose distributions in multiple planes were determined for three different plaque
models (CCB, CCA, and COB), and three different plaques per model, using EBT3
films in an in-house developed polystyrene phantom and the mcnp6 MC code. Dose
difference maps were generated to analyze interplaque variations for a specific
type, and for comparing measurements against MC simulations. Furthermore, dose
distributions were validated against values specified by the manufacturer (BEBIG)
and microdiamond and diode measurements in a water scanning phantom. Radial
profiles were assessed and used to estimate dosimetric margins for a given
combination of representative tumor geometry and plaque size. RESULTS: Absolute
dose rates at a reference depth of 2 mm on the central axis of the plaque show an
agreement better than 5% (10%) when comparing film measurements (mcnp6) to the
manufacturer's data. The reproducibility of depth-dose profile measurements was
<7% (2 SD) for all investigated detectors and plaque types. Dose difference maps
revealed minor interplaque deviations for a specific plaque type due to
inhomogeneities of the active layer. The evaluation of dosimetric margins showed
that for a majority of the investigated cases, the tumor was not completely
covered by the 100% isodose prescribed to the tumor apex if the difference
between geometrical plaque size and tumor base <=4 mm. CONCLUSIONS: EBT3 film
dosimetry in an in-house developed phantom was successfully used to characterize
the dosimetric properties of different (106)Ru plaque models. The film
measurements were validated against MC calculations and other experimental
methods and showed a good agreement with data from BEBIG well within published
tolerances. The dosimetric information as well as interplaque comparison can be
used for comprehensive quality assurance and for considerations in the treatment
planning of ophthalmic brachytherapy.
PMID- 26429256
TI - Increasing efficiency of BEAMnrc-simulated Co-60 beams using directional source
biasing.
AB - PURPOSE: This study describes the implementation of a directional source biasing
(DSB) scheme for efficiently simulating Cobalt-60 treatment heads using the
BEAMnrc Monte Carlo code. Previous simulation of Co-60 beams with BEAMnrc was
impractical because of the time required to track photons not directed into the
treatment field and to simulate secondary charged particles. METHODS: In DSB,
efficiency is increased by splitting each photon emitted by the Co-60 source a
user-defined number of times. Only those split primary photons directed into a
user-defined splitting field (encompassing the treatment field) are sampled,
yielding many low-weight photons directed into the field. Efficiency can be
further increased by taking advantage of radial symmetry at the top of the
treatment head to reduce the number of split primary photons tracked in this
portion. There is also an option to generate contaminant electrons in DSB.
RESULTS: The DSB scheme in BEAMnrc increases the photon fluence calculation
efficiency in a 10 * 10 cm(2) Co-60 beam by a factor of 1800 with a concurrent
increase in contaminant electron fluence calculation efficiency by a factor of
1200. Implementation of DSB in beampp, a C++ code for accelerator simulations
based on EGSnrc and the C++ class library, egspp, increases photon fluence
efficiency by a factor of 2800 and contaminant electron fluence efficiency by a
factor of 1600. Optimum splitting numbers are in the range of 20,000-40,000. For
dose calculations in a water phantom (0.5 * 0.5 * 0.5 cm(3) voxels) this
translates into a factor of ~400 increase in dose calculation efficiency (all
doses > 0.5 * Dmax). An example calculation of the ratio of dose to water to dose
to chamber (the basis of the beam quality correction factor) to within 0.2% in a
realistic chamber using a full simulation of a Co-60 treatment head as a source
indicates the practicality of Co-60 simulations with DSB. CONCLUSIONS: The
efficiency improvement resulting from DSB makes Monte Carlo commissioning of Co
60 beams and calculation of beam quality correction factors feasible.
PMID- 26429255
TI - Estimating patient-specific and anatomically correct reference model for
craniomaxillofacial deformity via sparse representation.
AB - PURPOSE: A significant number of patients suffer from craniomaxillofacial (CMF)
deformity and require CMF surgery in the United States. The success of CMF
surgery depends on not only the surgical techniques but also an accurate surgical
planning. However, surgical planning for CMF surgery is challenging due to the
absence of a patient-specific reference model. Currently, the outcome of the
surgery is often subjective and highly dependent on surgeon's experience. In this
paper, the authors present an automatic method to estimate an anatomically
correct reference shape of jaws for orthognathic surgery, a common type of CMF
surgery. METHODS: To estimate a patient-specific jaw reference model, the authors
use a data-driven method based on sparse shape composition. Given a dictionary of
normal subjects, the authors first use the sparse representation to represent the
midface of a patient by the midfaces of the normal subjects in the dictionary.
Then, the derived sparse coefficients are used to reconstruct a patient-specific
reference jaw shape. RESULTS: The authors have validated the proposed method on
both synthetic and real patient data. Experimental results show that the authors'
method can effectively reconstruct the normal shape of jaw for patients.
CONCLUSIONS: The authors have presented a novel method to automatically estimate
a patient-specific reference model for the patient suffering from CMF deformity.
PMID- 26429257
TI - Characterization of the onboard imaging unit for the first clinical magnetic
resonance image guided radiation therapy system.
AB - PURPOSE: To characterize the performance of the onboard imaging unit for the
first clinical magnetic resonance image guided radiation therapy (MR-IGRT)
system. METHODS: The imaging performance characterization included four
components: ACR (the American College of Radiology) phantom test, spatial
integrity, coil signal to noise ratio (SNR) and uniformity, and magnetic field
homogeneity. The ACR phantom test was performed in accordance with the ACR
phantom test guidance. The spatial integrity test was evaluated using a 40.8 *
40.8 * 40.8 cm(3) spatial integrity phantom. MR and computed tomography (CT)
images of the phantom were acquired and coregistered. Objects were identified
around the surfaces of 20 and 35 cm diameters of spherical volume (DSVs) on both
the MR and CT images. Geometric distortion was quantified using deviation in
object location between the MR and CT images. The coil SNR test was performed
according to the national electrical manufacturers association (NEMA) standards
MS-1 and MS-9. The magnetic field homogeneity test was measured using field
camera and spectral peak methods. RESULTS: For the ACR tests, the slice position
error was less than 0.10 cm, the slice thickness error was less than 0.05 cm, the
resolved high-contrast spatial resolution was 0.09 cm, the resolved low-contrast
spokes were more than 25, the image intensity uniformity was above 93%, and the
percentage ghosting was less than 0.22%. All were within the ACR recommended
specifications. The maximum geometric distortions within the 20 and 35 cm DSVs
were 0.10 and 0.18 cm for high spatial resolution three-dimensional images and
0.08 and 0.20 cm for high temporal resolution two dimensional cine images based
on the distance-to-phantom-center method. The average SNR was 12.0 for the body
coil, 42.9 for the combined torso coil, and 44.0 for the combined head and neck
coil. Magnetic field homogeneities at gantry angles of 0 degrees , 30 degrees ,
60 degrees , 90 degrees , and 120 degrees were 23.55, 20.43, 18.76, 19.11, and
22.22 ppm, respectively, using the field camera method over the 45 cm DSV.
CONCLUSIONS: The onboard imaging unit of the first commercial MR-IGRT system
meets ACR, NEMA, and vendor specifications.
PMID- 26429258
TI - Calibration of EBT2 film using a red-channel PDD method in combination with a
modified three-channel technique.
AB - PURPOSE: Ashland Inc. EBT2 and EBT3 films are widely used in quality assurance
for radiation therapy; however, there remains a relatively high degree of
uncertainty [B. Hartmann, M. Martisikova, and O. Jakel, "Homogeneity of
Gafchromic EBT2 film," Med. Phys. 37, 1753-1756 (2010)]. Micke et al. (2011)
recently improved the spatial homogeneity using all color channels of a flatbed
scanner; however, van Hoof et al. (2012) pointed out that the corrected
nonuniformity still requires further investigation for larger fields. To reduce
the calibration errors and the uncertainty, the authors propose a new red-channel
percentage-depth-dose method in combination with a modified three-channel
technique. METHODS: For the ease of comparison, the EBT2 film image used in the
authors' previous study (2012) was reanalyzed using different approaches. Photon
beams of 6-MV were delivered to two different films at two different beam on
times, resulting in the absorption doses of ranging from approximately 30 to 300
cGy at the vertical midline of the film, which was set to be coincident with the
central axis of the beam. The film was tightly sandwiched in a 30(3)-cm(3)
polystyrene phantom, and the pixel values for red, green, and blue channels were
extracted from 234 points on the central axis of the beam and compared with the
corresponding depth doses. The film was first calibrated using the multichannel
method proposed by Micke et al. (2010), accounting for nonuniformities in the
scanner. After eliminating the scanner and dose-independent nonuniformities, the
film was recalibrated via the dose-dependent optical density of the red channel
and fitted to a power function. This calibration was verified via comparisons of
the dose profiles extracted from the films, where three were exposed to a 60
degrees physical wedge field and three were exposed to composite fields, and all
of which were measured in a water phantom. A correction for optical attenuation
was implemented, and treatment plans of intensity modulated radiation therapy and
volumetric modulated arc therapy were evaluated. RESULTS: The method described
here demonstrated improved accuracy with reduced uncertainty. The relative error
compared with the measurements of a water phantom was less than 1%, and the
overall calibration uncertainty was less than 2%. Verification tests revealed
that the results were close to those of the authors' previous study, and all
differences were within 3%, except those with a high-dose gradient. The gamma
pass rates (2%/2 mm) of the treatment plan evaluated using the method described
here were greater than 99%, and no obvious stripe patterns were observed in the
dose-difference maps. CONCLUSIONS: Spatial homogeneity was significantly improved
via the calibration method described here. This technique is both convenient and
time-efficient because it does not require cutting the film, and only two
exposures are necessary.
PMID- 26429259
TI - A two-stage method for microcalcification cluster segmentation in mammography by
deformable models.
AB - PURPOSE: Segmentation of microcalcification (MC) clusters in x-ray mammography is
a difficult task for radiologists. Accurate segmentation is prerequisite for
quantitative image analysis of MC clusters and subsequent feature extraction and
classification in computer-aided diagnosis schemes. METHODS: In this study, a two
stage semiautomated segmentation method of MC clusters is investigated. The first
stage is targeted to accurate and time efficient segmentation of the majority of
the particles of a MC cluster, by means of a level set method. The second stage
is targeted to shape refinement of selected individual MCs, by means of an active
contour model. Both methods are applied in the framework of a rich scale-space
representation, provided by the wavelet transform at integer scales. Segmentation
reliability of the proposed method in terms of inter and intraobserver agreements
was evaluated in a case sample of 80 MC clusters originating from the digital
database for screening mammography, corresponding to 4 morphology types
(punctate: 22, fine linear branching: 16, pleomorphic: 18, and amorphous: 24) of
MC clusters, assessing radiologists' segmentations quantitatively by two distance
metrics (Hausdorff distance-HDISTcluster, average of minimum distance
AMINDISTcluster) and the area overlap measure (AOMcluster). The effect of the
proposed segmentation method on MC cluster characterization accuracy was
evaluated in a case sample of 162 pleomorphic MC clusters (72 malignant and 90
benign). Ten MC cluster features, targeted to capture morphologic properties of
individual MCs in a cluster (area, major length, perimeter, compactness, and
spread), were extracted and a correlation-based feature selection method yielded
a feature subset to feed in a support vector machine classifier. Classification
performance of the MC cluster features was estimated by means of the area under
receiver operating characteristic curve (Az +/- Standard Error) utilizing tenfold
cross-validation methodology. A previously developed B-spline active rays
segmentation method was also considered for comparison purposes. RESULTS:
Interobserver and intraobserver segmentation agreements (median and [25%, 75%]
quartile range) were substantial with respect to the distance metrics
HDISTcluster (2.3 [1.8, 2.9] and 2.5 [2.1, 3.2] pixels) and AMINDISTcluster (0.8
[0.6, 1.0] and 1.0 [0.8, 1.2] pixels), while moderate with respect to AOMcluster
(0.64 [0.55, 0.71] and 0.59 [0.52, 0.66]). The proposed segmentation method
outperformed (0.80 +/- 0.04) statistically significantly (Mann-Whitney U-test, p
< 0.05) the B-spline active rays segmentation method (0.69 +/- 0.04), suggesting
the significance of the proposed semiautomated method. CONCLUSIONS: Results
indicate a reliable semiautomated segmentation method for MC clusters offered by
deformable models, which could be utilized in MC cluster quantitative image
analysis.
PMID- 26429260
TI - Projections onto the Pareto surface in multicriteria radiation therapy
optimization.
AB - PURPOSE: To eliminate or reduce the error to Pareto optimality that arises in
Pareto surface navigation when the Pareto surface is approximated by a small
number of plans. METHODS: The authors propose to project the navigated plan onto
the Pareto surface as a postprocessing step to the navigation. The projection
attempts to find a Pareto optimal plan that is at least as good as or better than
the initial navigated plan with respect to all objective functions. An augmented
form of projection is also suggested where dose-volume histogram constraints are
used to prevent that the projection causes a violation of some clinical goal. The
projections were evaluated with respect to planning for intensity modulated
radiation therapy delivered by step-and-shoot and sliding window and spot-scanned
intensity modulated proton therapy. Retrospective plans were generated for a
prostate and a head and neck case. RESULTS: The projections led to improved dose
conformity and better sparing of organs at risk (OARs) for all three delivery
techniques and both patient cases. The mean dose to OARs decreased by 3.1 Gy on
average for the unconstrained form of the projection and by 2.0 Gy on average
when dose-volume histogram constraints were used. No consistent improvements in
target homogeneity were observed. CONCLUSIONS: There are situations when Pareto
navigation leaves room for improvement in OAR sparing and dose conformity, for
example, if the approximation of the Pareto surface is coarse or the problem
formulation has too permissive constraints. A projection onto the Pareto surface
can identify an inaccurate Pareto surface representation and, if necessary,
improve the quality of the navigated plan.
PMID- 26429261
TI - Induced magnetic moment in stainless steel components of orthodontic appliances
in 1.5 T MRI scanners.
AB - PURPOSE: Most orthodontic appliances are made of stainless steel materials and
induce severe magnetic susceptibility artifacts in brain MRI. In an effort for
correcting these artifacts, it is important to know the value of induced magnetic
moments in all parts of orthodontic appliances. In this study, the induced
magnetic moment of stainless steel orthodontic brackets, molar bands, and arch
wires from several vendors is measured. METHODS: Individual stainless steel
brackets, molar bands, and short segments of arch-wire were positioned in the
center of spherical flask filled with water through a thin plastic rod. The
induced magnetic moment at 1.5 T was determined by fitting the B0 map to the z
component of the magnetic dipole field using a computer routine. RESULTS: The
induced magnetic moment at 1.5 T was dominated by the longitudinal component mz,
with a small contribution from the transverse components. The mz was insensitive
to the orientation of the metal parts. The orthodontic brackets collectively
dominated the magnetic dipole moment in orthodontic appliances. In brackets from
six vendors, the total induced mz from 20 brackets for nonmolar teeth ranged from
0.108 to 0.158 (median 0.122) A ? m(2). The mz in eight molar bands with bracket
attachment from two vendors ranged from 0.0004 to 0.0166 (median 0.0035) A ?
m(2). Several full length arch wires had induced magnetic moment in the range of
0.006-0.025 (median 0.015) A ? m(2). CONCLUSIONS: Orthodontic brackets
collectively contributed most to the total magnetic moment. Different types of
brackets, molar bands, and arch wires all exhibit substantial variability in the
induced magnetic moment.
PMID- 26429262
TI - Vision 20/20: Simultaneous CT-MRI--Next chapter of multimodality imaging.
AB - Multimodality imaging systems such as positron emission tomography-computed
tomography (PET-CT) and MRI-PET are widely available, but a simultaneous CT-MRI
instrument has not been developed. Synergies between independent modalities,
e.g., CT, MRI, and PET/SPECT can be realized with image registration, but such
postprocessing suffers from registration errors that can be avoided with
synchronized data acquisition. The clinical potential of simultaneous CT-MRI is
significant, especially in cardiovascular and oncologic applications where
studies of the vulnerable plaque, response to cancer therapy, and kinetic and
dynamic mechanisms of targeted agents are limited by current imaging
technologies. The rationale, feasibility, and realization of simultaneous CT-MRI
are described in this perspective paper. The enabling technologies include
interior tomography, unique gantry designs, open magnet and RF sequences, and
source and detector adaptation. Based on the experience with PET-CT, PET-MRI, and
MRI-LINAC instrumentation where hardware innovation and performance optimization
were instrumental to construct commercial systems, the authors provide top-level
concepts for simultaneous CT-MRI to meet clinical requirements and new
challenges. Simultaneous CT-MRI fills a major gap of modality coupling and
represents a key step toward the so-called "omnitomography" defined as the
integration of all relevant imaging modalities for systems biology and precision
medicine.
PMID- 26429264
TI - Local respiratory motion correction for PET/CT imaging: Application to lung
cancer.
AB - PURPOSE: Despite multiple methodologies already proposed to correct respiratory
motion in the whole PET imaging field of view (FOV), such approaches have not
found wide acceptance in clinical routine. An alternative can be the local
respiratory motion correction (LRMC) of data corresponding to a given volume of
interest (VOI: organ or tumor). Advantages of LRMC include the use of a simple
motion model, faster execution times, and organ specific motion correction. The
purpose of this study was to evaluate the performance of LMRC using various
motion models for oncology (lung lesion) applications. METHODS: Both simulated
(NURBS based 4D cardiac-torso phantom) and clinical studies (six patients) were
used in the evaluation of the proposed LRMC approach. PET data were acquired in
list-mode and synchronized with respiration. The implemented approach consists
first in defining a VOI on the reconstructed motion average image. Gated PET
images of the VOI are subsequently reconstructed using only lines of response
passing through the selected VOI and are used in combination with a center of
gravity or an affine/elastic registration algorithm to derive the transformation
maps corresponding to the respiration effects. Those are finally integrated in
the reconstruction process to produce a motion free image over the lesion
regions. RESULTS: Although the center of gravity or affine algorithm achieved
similar performance for individual lesion motion correction, the elastic model,
applied either locally or to the whole FOV, led to an overall superior
performance. The spatial tumor location was altered by 89% and 81% for the
elastic model applied locally or to the whole FOV, respectively (compared to 44%
and 39% for the center of gravity and affine models, respectively). This resulted
in similar associated overall tumor volume changes of 84% and 80%, respectively
(compared to 75% and 71% for the center of gravity and affine models,
respectively). The application of the nonrigid deformation model in LRMC led to
over an order of magnitude gain in computational efficiency of the correction
relative to the application of the deformable model to the whole FOV.
CONCLUSIONS: The results of this study support the use of LMRC as a flexible and
efficient correction approach for respiratory motion effects for single lesions
in the thoracic area.
PMID- 26429263
TI - Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons,
megavoltage photons, and kilovoltage photons.
AB - PURPOSE: The purpose of this work is to investigate the radiosensitizing effect
of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage
(MV) photon, and kilovoltage (kV) photon irradiation. METHODS: Monte Carlo
simulations were carried out using tool for particle simulation (TOPAS) to obtain
the spatial dose distribution in close proximity up to 20 MUm from the GNPs. The
spatial dose distribution from GNPs was used as an input to calculate the dose
deposited to the blood vessels. GNP induced vasculature damage was evaluated for
three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV
photon beam, and two kV photon beams). For each particle source, various depths
in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14,
and 20 MUm) were investigated. Two GNP distributions in lumen were considered,
either homogeneously distributed in the vessel or attached to the inner wall of
the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo
enhancement studies and conventional clinical fractionation, respectively.
RESULTS: These simulations showed that for 20 Au-mg/g GNP blood concentration
homogeneously distributed in the vessel, the additional dose at the inner
vascular wall encircling the lumen was 43% of the prescribed dose at the depth of
treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1%
for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular
wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more
dose in the vascular wall at 20 cm depth in water as compared to at depth of
maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the
vascular wall for all depths across the spread out Bragg peak with 12.7 cm range
and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter
GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When
the GNPs were attached to the inner vascular wall, the damage to the inner
vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon
source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though
the average dose increase from the proton beam and MV photon beam was not large,
there were high dose spikes that elevate the local dose of the parts of the blood
vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the
GNPs can be actively targeted to the endothelial cells. CONCLUSIONS: GNPs can
potentially be used to enhance radiation therapy by causing vasculature damage
through high dose spikes caused by the addition of GNPs especially for
hypofractionated treatment. If GNPs are designed to actively accumulate at the
tumor vasculature walls, vasculature damage can be increased significantly. The
largest enhancement is seen using kilovoltage photons due to the photoelectric
effect. Although no significant average dose enhancement was observed for the
whole vasculature structure for both MV photons and protons, they can cause high
local dose escalation (>15 Gy) to areas of the blood vessel that can potentially
contribute to the disruption of the functionality of the blood vessels in the
tumor.
PMID- 26429265
TI - Technical Note: Characterization of custom 3D printed multimodality imaging
phantoms.
AB - PURPOSE: Imaging phantoms are important tools for researchers and technicians,
but they can be costly and difficult to customize. Three dimensional (3D)
printing is a widely available rapid prototyping technique that enables the
fabrication of objects with 3D computer generated geometries. It is ideal for
quickly producing customized, low cost, multimodal, reusable imaging phantoms.
This work validates the use of 3D printed phantoms by comparing CT and PET scans
of a 3D printed phantom and a commercial "Micro Deluxe" phantom. This report also
presents results from a customized 3D printed PET/MRI phantom, and a customized
high resolution imaging phantom with sub-mm features. METHODS: CT and PET scans
of a 3D printed phantom and a commercial Micro Deluxe (Data Spectrum Corporation,
USA) phantom with 1.2, 1.6, 2.4, 3.2, 4.0, and 4.8 mm diameter hot rods were
acquired. The measured PET and CT rod sizes, activities, and attenuation
coefficients were compared. A PET/MRI scan of a custom 3D printed phantom with
hot and cold rods was performed, with photon attenuation and normalization
measurements performed with a separate 3D printed normalization phantom. X-ray
transmission scans of a customized two level high resolution 3D printed phantom
with sub-mm features were also performed. RESULTS: Results show very good
agreement between commercial and 3D printed micro deluxe phantoms with less than
3% difference in CT measured rod diameter, less than 5% difference in PET
measured rod diameter, and a maximum of 6.2% difference in average rod activity
from a 10 min, 333 kBq/ml (9 MUCi/ml) Siemens Inveon (Siemens Healthcare,
Germany) PET scan. In all cases, these differences were within the measurement
uncertainties of our setups. PET/MRI scans successfully identified 3D printed hot
and cold rods on PET and MRI modalities. X-ray projection images of a 3D printed
high resolution phantom identified features as small as 350 MUm wide.
CONCLUSIONS: This work shows that 3D printed phantoms can be functionally
equivalent to commercially available phantoms. They are a viable option for
quickly distributing and fabricating low cost, customized phantoms.
PMID- 26429266
TI - Influence of radiation dose and reconstruction algorithm in MDCT assessment of
airway wall thickness: A phantom study.
AB - PURPOSE: Wall thickness (WT) is an airway feature of great interest for the
assessment of morphological changes in the lung parenchyma. Multidetector
computed tomography (MDCT) has recently been used to evaluate airway WT, but the
potential risk of radiation-induced carcinogenesis-particularly in younger
patients-might limit a wider use of this imaging method in clinical practice. The
recent commercial implementation of the statistical model-based iterative
reconstruction (MBIR) algorithm, instead of the conventional filtered back
projection (FBP) algorithm, has enabled considerable radiation dose reduction in
many other clinical applications of MDCT. The purpose of this work was to study
the impact of radiation dose and MBIR in the MDCT assessment of airway WT.
METHODS: An airway phantom was scanned using a clinical MDCT system (Discovery
CT750 HD, GE Healthcare) at 4 kV levels and 5 mAs levels. Both FBP and a
commercial implementation of MBIR (Veo(TM), GE Healthcare) were used to
reconstruct CT images of the airways. For each kV-mAs combination and each
reconstruction algorithm, the contrast-to-noise ratio (CNR) of the airways was
measured, and the WT of each airway was measured and compared with the nominal
value; the relative bias and the angular standard deviation in the measured WT
were calculated. For each airway and reconstruction algorithm, the overall
performance of WT quantification across all of the 20 kV-mAs combinations was
quantified by the sum of squares (SSQs) of the difference between the measured
and nominal WT values. Finally, the particular kV-mAs combination and
reconstruction algorithm that minimized radiation dose while still achieving a
reference WT quantification accuracy level was chosen as the optimal acquisition
and reconstruction settings. RESULTS: The wall thicknesses of seven airways of
different sizes were analyzed in the study. Compared with FBP, MBIR improved the
CNR of the airways, particularly at low radiation dose levels. For FBP, the
relative bias and the angular standard deviation of the measured WT increased
steeply with decreasing radiation dose. Except for the smallest airway, MBIR
enabled significant reduction in both the relative bias and angular standard
deviation of the WT, particularly at low radiation dose levels; the SSQ was
reduced by 50%-96% by using MBIR. The optimal reconstruction algorithm was found
to be MBIR for the seven airways being assessed, and the combined use of MBIR and
optimal kV-mAs selection resulted in a radiation dose reduction of 37%-83%
compared with a reference scan protocol with a dose level of 1 mGy. CONCLUSIONS:
The quantification accuracy of airway WT is strongly influenced by radiation dose
and reconstruction algorithm. The MBIR algorithm potentially allows the desired
WT quantification accuracy to be achieved with reduced radiation dose, which may
enable a wider clinical use of MDCT for the assessment of airway WT, particularly
for younger patients who may be more sensitive to exposures with ionizing
radiation.
PMID- 26429267
TI - Spatial fractionation of the dose using neon and heavier ions: A Monte Carlo
study.
AB - PURPOSE: This work explores a new radiation therapy approach which might trigger
a renewed use of neon and heavier ions to treat cancers. These ions were shown to
be extremely efficient in radioresistant tumor killing. Unfortunately, the
efficient region also extends into the normal tissue in front of the tumor. The
strategy the authors propose is to profit from the well-established sparing
effect of thin spatially fractionated beams, so that the impact on normal tissues
might be minimized while a high tumor control is achieved. The main goal of this
work is to provide a proof of concept of this new approach. With that aim, a
dosimetric study was carried out as a first step to evaluate the interest of
further explorations of this avenue. METHODS: The gate/geant4 v.6.1 Monte Carlo
simulation platform was employed to simulate arrays of rectangular minibeams (700
MUm * 2 cm) of four ions (Ne, Si, Ar, and Fe). The irradiations were performed
with a 2 cm-long spread-out Bragg peak centered at 7 cm-depth. Dose distributions
in a water phantom were scored considering two minibeams center-to-center
distances: 1400 and 3500 MUm. Peak and valley doses, peak-to-valley dose ratios
(PVDRs), beam penumbras, and relative contribution of nuclear fragments and
electromagnetic processes were assessed as figures of merit. In addition, the
type and proportion of the secondary nuclear fragments were evaluated in both
peak and valley regions. RESULTS: Extremely high PVDR values (>100) and low
valley doses were obtained. The higher the atomic number (Z) of the primary ion
is, the lower the valleys and the narrower the penumbras. Although the yield of
secondary nuclear products increases with Z, the actual dose being deposited by
the secondary nuclear fragments in the valleys starts to be the dominant
contribution at deeper points, helping in the sparing of proximal normal tissues.
Additionally, a wider center-to-center distance leads to a minimized contribution
of heavier secondary fragments in valleys. CONCLUSIONS: The computed dose
distributions suggest that a spatial fractionation of the dose combined to the
use of submillimetric field sizes might allow profiting from the high efficiency
of neon and heavier ions for the treatment of radioresistant tumors, while
preserving normal tissues. The authors' results support the further exploration
of this avenue. Next steps include the realization of biological experiment to
confirm the shifting of normal tissue complication probability curves.
PMID- 26429268
TI - Measurement of gold nanofilm dose enhancement using unlaminated radiochromic
film.
AB - PURPOSE: Bombarding high-Z material with x-ray radiation releases Auger electrons
and Coster-Kronig electrons, along with deeper penetrating fluorescent x-rays and
photoelectrons. The Auger and Coster-Kronig electron penetration distance is on
the order of nanometers to micrometers in water or tissue, creating a large dose
enhancement accompanied by a RBE greater than 1 at the cellular level. The
authors' aim is to measure the gold nanofilm dose enhancement factor (DEF) at the
cellular level with unlaminated radiochromic film via primary 50 kVp tungsten x
ray spectrum interaction, similar to an electronic brachytherapy spectrum.
METHODS: Unlaminated Gafchromic((r)) EBT2 film and Monte Carlo modeling were
combined to derive DEF models. Gold film of thickness 23.1 +/- 4.3 nm and
surface roughness of 1.2 +/- 0.2 nm was placed in contact with unlaminated
radiochromic film in a downstream orientation and exposed to a 50 kVp tungsten
bremsstrahlung, mean energy 19.2 keV. Film response correction factors were
derived by Monte Carlo modeling of electron energy deposition in the film's
active layer, and by measuring film energy dependence from 4.5 keV to 50 kVp.
RESULTS: The measured DEF within a 13.6 MUm thick water layer was 0.29 with a
mean dose of 94 +/- 9.4 cGy from Au emissions and 324 +/- 32.4 cGy from the 50
kVp primary beam. Monte Carlo derived correction factors allowed determination of
Au contributed dose in shallower depths at 0.25 MUm intervals. Maximum DEF of
18.31 was found in the first 0.25 MUm water depth. CONCLUSIONS: Dose enhancement
from Au nanofilm can be measured at the cellular level using unlaminated
radiochromic film. Complementing the measured dose value with Monte Carlo
calculations allows estimation of dose enhancement at depth increments within the
cellular range.
PMID- 26429269
TI - DECT evaluation of noncalcified coronary artery plaque.
AB - PURPOSE: Composition of the coronary artery plaque is known to have critical role
in heart attack. While calcified plaque can easily be diagnosed by conventional
CT, it fails to distinguish between fibrous and lipid rich plaques. In the
present paper, the authors discuss the experimental techniques and obtain a
numerical algorithm by which the electron density (rho(e)) and the effective
atomic number (Z(eff)) can be obtained from the dual energy computed tomography
(DECT) data. The idea is to use this inversion method to characterize and
distinguish between the lipid and fibrous coronary artery plaques. METHODS: For
the purpose of calibration of the CT machine, the authors prepare aqueous samples
whose calculated values of (rho(e), Z(eff)) lie in the range of (2.65 * 10(23) <=
rho(e) <= 3.64 * 10(23)/cm(3)) and (6.80 <= Z(eff) <= 8.90). The authors fill the
phantom with these known samples and experimentally determine HU(V1) and HU(V2),
with V1,V2 = 100 and 140 kVp, for the same pixels and thus determine the
coefficients of inversion that allow us to determine (rho(e), Z(eff)) from the
DECT data. The HU(100) and HU(140) for the coronary artery plaque are obtained by
filling the channel of the coronary artery with a viscous solution of methyl
cellulose in water, containing 2% contrast. These (rho(e), Z(eff)) values of the
coronary artery plaque are used for their characterization on the basis of
theoretical models of atomic compositions of the plaque materials. These results
are compared with histopathological report. RESULTS: The authors find that the
calibration gives rho(e) with an accuracy of +/-3.5% while Z(eff) is found within
+/-1% of the actual value, the confidence being 95%. The HU(100) and HU(140) are
found to be considerably different for the same plaque at the same position and
there is a linear trend between these two HU values. It is noted that pure lipid
type plaques are practically nonexistent, and microcalcification, as observed in
histopathology, has to be taken into account to explain the nature of the
observed (rho(e), Z(eff)) data. This also enables us to judge the composition of
the plaque in terms of basic model which considers the plaque to be composed of
fibres, lipids, and microcalcification. CONCLUSIONS: This simple and reliable
method has the potential as an effective modality to investigate the composition
of noncalcified coronary artery plaques and thus help in their characterization.
In this inversion method, (rho(e), Z(eff)) of the scanned sample can be found by
eliminating the effects of the CT machine and also by ensuring that the
determination of the two unknowns (rho(e), Ze(ff)) does not interfere with each
other and the nature of the plaque can be identified in terms of a three
component model.
PMID- 26429270
TI - Technical Note: Characterization and correction of gradient nonlinearity induced
distortion on a 1.0 T open bore MR-SIM.
AB - PURPOSE: Distortions in magnetic resonance imaging (MRI) compromise spatial
fidelity, potentially impacting delineation and dose calculation. We
characterized 2D and 3D large field of view (FOV), sequence-independent
distortion at various positions in a 1.0 T high-field open MR simulator (MR-SIM)
to implement correction maps for MRI treatment planning. METHODS: A 36 * 43 * 2
cm(3) phantom with 255 known landmarks (~1 mm(3)) was scanned using 1.0 T high
field open MR-SIM at isocenter in the transverse, sagittal, and coronal axes, and
a 465 * 350 * 168 mm(3) 3D phantom was scanned by stepping in the superior
inferior direction in three overlapping positions to achieve a total 465 * 350 *
400 mm(3) sampled FOV yielding >13 800 landmarks (3D Gradient-Echo, TE/TR/alpha =
5.54 ms/30 ms/28 degrees , voxel size = 1 * 1 * 2 mm(3)). A binary template
(reference) was generated from a phantom schematic. An automated program
converted MR images to binary via masking, thresholding, and testing for
connectivity to identify landmarks. Distortion maps were generated by centroid
mapping. Images were corrected via warping with inverse distortion maps, and
temporal stability was assessed. RESULTS: Over the sampled FOV, non-negligible
residual gradient distortions existed as close as 9.5 cm from isocenter, with a
maximum distortion of 7.4 mm as close as 23 cm from isocenter. Over six months,
average gradient distortions were -0.07 +/- 1.10 mm and 0.10 +/- 1.10 mm in the x
and y directions for the transverse plane, 0.03 +/- 0.64 and -0.09 +/- 0.70 mm in
the sagittal plane, and 0.4 +/- 1.16 and 0.04 +/- 0.40 mm in the coronal plane.
After implementing 3D correction maps, distortions were reduced to <1 pixel width
(1 mm) for all voxels up to 25 cm from magnet isocenter. CONCLUSIONS: Inherent
distortion due to gradient nonlinearity was found to be non-negligible even with
vendor corrections applied, and further corrections are required to obtain 1 mm
accuracy for large FOVs. Statistical analysis of temporal stability shows that
sequence independent distortion maps are consistent within six months of
characterization.
PMID- 26429271
TI - Quality control for quantitative multicenter whole-body PET/MR studies: A NEMA
image quality phantom study with three current PET/MR systems.
AB - PURPOSE: Integrated positron emission tomography/magnetic resonance (PET/MR)
systems derive the PET attenuation correction (AC) from dedicated MR sequences.
While MR-AC performs reasonably well in clinical patient imaging, it may fail for
phantom-based quality control (QC). The authors assess the applicability of
different protocols for PET QC in multicenter PET/MR imaging. METHODS: The
National Electrical Manufacturers Association NU 2 2007 image quality phantom was
imaged on three combined PET/MR systems: a Philips Ingenuity TF PET/MR, a Siemens
Biograph mMR, and a GE SIGNA PET/MR (prototype) system. The phantom was filled
according to the EANM FDG-PET/CT guideline 1.0 and scanned for 5 min over 1 bed.
Two MR-AC imaging protocols were tested: standard clinical procedures and a
dedicated protocol for phantom tests. Depending on the system, the dedicated
phantom protocol employs a two-class (water and air) segmentation of the MR data
or a CT-based template. Differences in attenuation- and SUV recovery coefficients
(RC) are reported. PET/CT-based simulations were performed to simulate the
various artifacts seen in the AC maps (MU-map) and their impact on the accuracy
of phantom-based QC. RESULTS: Clinical MR-AC protocols caused substantial errors
and artifacts in the AC maps, resulting in underestimations of the reconstructed
PET activity of up to 27%, depending on the PET/MR system. Using dedicated
phantom MR-AC protocols, PET bias was reduced to -8%. Mean and max SUV RC met
EARL multicenter PET performance specifications for most contrast objects, but
only when using the dedicated phantom protocol. Simulations confirmed the bias in
experimental data to be caused by incorrect AC maps resulting from the use of
clinical MR-AC protocols. CONCLUSIONS: Phantom-based quality control of PET/MR
systems in a multicenter, multivendor setting may be performed with sufficient
accuracy, but only when dedicated phantom acquisition and processing protocols
are used for attenuation correction.
PMID- 26429272
TI - The SRT reconstruction algorithm for semiquantification in PET imaging.
AB - PURPOSE: The spline reconstruction technique (SRT) is a new, fast algorithm based
on a novel numerical implementation of an analytic representation of the inverse
Radon transform. The mathematical details of this algorithm and comparisons with
filtered backprojection were presented earlier in the literature. In this study,
the authors present a comparison between SRT and the ordered-subsets expectation
maximization (OSEM) algorithm for determining contrast and semiquantitative
indices of (18)F-FDG uptake. METHODS: The authors implemented SRT in the software
for tomographic image reconstruction (stir) open-source platform and evaluated
this technique using simulated and real sinograms obtained from the GE Discovery
ST positron emission tomography/computer tomography scanner. All simulations and
reconstructions were performed in stir. For OSEM, the authors used the clinical
protocol of their scanner, namely, 21 subsets and two iterations. The authors
also examined images at one, four, six, and ten iterations. For the simulation
studies, the authors analyzed an image-quality phantom with cold and hot lesions.
Two different versions of the phantom were employed at two different hot-sphere
lesion-to-background ratios (LBRs), namely, 2:1 and 4:1. For each noiseless
sinogram, 20 Poisson realizations were created at five different noise levels. In
addition to making visual comparisons of the reconstructed images, the authors
determined contrast and bias as a function of the background image roughness
(IR). For the real-data studies, sinograms of an image-quality phantom simulating
the human torso were employed. The authors determined contrast and LBR as a
function of the background IR. Finally, the authors present plots of contrast as
a function of IR after smoothing each reconstructed image with Gaussian filters
of six different sizes. Statistical significance was determined by employing the
Wilcoxon rank-sum test. RESULTS: In both simulated and real studies, SRT exhibits
higher contrast and lower bias than OSEM at the cold lesions. This improvement is
achieved at the expense of increasing the noise in the reconstructed images. For
the hot lesions, SRT exhibits a small improvement in contrast and LBR over OSEM
with 21 subsets and two iterations; however, this improvement is not
statistically significant. As the number of iterations increases, the performance
of OSEM improves over SRT but again without statistical significance. The curves
of contrast and LBR as a function of IR after Gaussian blurring indicate that the
advantage of SRT in the cold regions is maintained even after decreasing the
noise level by Gaussian blurring. CONCLUSIONS: SRT, at the expense of slightly
increased noise in the reconstructed images, reconstructs images of higher
contrast and lower bias than the clinical protocol of OSEM. This improvement is
particularly evident for images involving cold regions. Thus, it appears that SRT
should be particularly useful for the quantification of low-count and cold
regions.
PMID- 26429273
TI - In-plane ultrasonic needle tracking using a fiber-optic hydrophone.
AB - PURPOSE: Accurate and efficient guidance of needles to procedural targets is
critically important during percutaneous interventional procedures. Ultrasound
imaging is widely used for real-time image guidance in a variety of clinical
contexts, but with this modality, uncertainties about the location of the needle
tip within the image plane lead to significant complications. Whilst several
methods have been proposed to improve the visibility of the needle, achieving
accuracy and compatibility with current clinical practice is an ongoing
challenge. In this paper, the authors present a method for directly visualizing
the needle tip using an integrated fiber-optic ultrasound receiver in conjunction
with the imaging probe used to acquire B-mode ultrasound images. METHODS: Needle
visualization and ultrasound imaging were performed with a clinical ultrasound
imaging system. A miniature fiber-optic ultrasound hydrophone was integrated into
a 20 gauge injection needle tip to receive transmissions from individual
transducer elements of the ultrasound imaging probe. The received signals were
reconstructed to create an image of the needle tip. Ultrasound B-mode imaging was
interleaved with needle tip imaging. A first set of measurements was acquired in
water and tissue ex vivo with a wide range of insertion angles (15 degrees -68
degrees ) to study the accuracy and sensitivity of the tracking method. A second
set was acquired in an in vivo swine model, with needle insertions to the
brachial plexus. A third set was acquired in an in vivo ovine model for fetal
interventions, with insertions to different locations within the uterine cavity.
Two linear ultrasound imaging probes were used: a 14-5 MHz probe for the first
and second sets, and a 9-4 MHz probe for the third. RESULTS: During insertions in
tissue ex vivo and in vivo, the imaged needle tip had submillimeter axial and
lateral dimensions. The signal-to-noise (SNR) of the needle tip was found to
depend on the insertion angle. With the needle tip in water, the SNR of the
needle tip varied with insertion angle, attaining values of 284 at 27 degrees
and 501 at 68 degrees . In swine tissue ex vivo, the SNR decreased from 80 at 15
degrees to 16 at 61 degrees . In swine tissue in vivo, the SNR varied with
depth, from 200 at 17.5 mm to 48 at 26 mm, with a constant insertion angle of 40
degrees . In ovine tissue in vivo, within the uterine cavity, the SNR varied from
46.4 at 25 mm depth to 18.4 at 32 mm depth, with insertion angles in the range of
26 degrees -65 degrees . CONCLUSIONS: A fiber-optic ultrasound receiver
integrated into the needle cannula in combination with single-element
transmissions from the imaging probe allows for direct visualization of the
needle tip within the ultrasound imaging plane. Visualization of the needle tip
was achieved at depths and insertion angles that are encountered during nerve
blocks and fetal interventions. The method presented in this paper has strong
potential to improve the safety and efficiency of ultrasound-guided needle
insertions.
PMID- 26429274
TI - Paddle-based rotating-shield brachytherapy.
AB - PURPOSE: The authors present a novel paddle-based rotating-shield brachytherapy
(P-RSBT) method, whose radiation-attenuating shields are formed with a multileaf
collimator (MLC), consisting of retractable paddles, to achieve intensity
modulation in high-dose-rate brachytherapy. METHODS: Five cervical cancer
patients using an intrauterine tandem applicator were considered to assess the
potential benefit of the P-RSBT method. The P-RSBT source used was a 50 kV
electronic brachytherapy source (Xoft AxxentTM). The paddles can be retracted
independently to form multiple emission windows around the source for radiation
delivery. The MLC was assumed to be rotatable. P-RSBT treatment plans were
generated using the asymmetric dose-volume optimization with smoothness control
method [Liu et al., Med. Phys. 41(11), 111709 (11pp.) (2014)] with a delivery
time constraint, different paddle sizes, and different rotation strides. The
number of treatment fractions (fx) was assumed to be five. As brachytherapy is
delivered as a boost for cervical cancer, the dose distribution for each case
includes the dose from external beam radiotherapy as well, which is 45 Gy in 25
fx. The high-risk clinical target volume (HR-CTV) doses were escalated until the
minimum dose to the hottest 2 cm(3) (D(2cm(3)) of either the rectum, sigmoid
colon, or bladder reached their tolerance doses of 75, 75, and 90 Gy3,
respectively, expressed as equivalent doses in 2 Gy fractions (EQD2 with
alpha/beta = 3 Gy). RESULTS: P-RSBT outperformed the two other RSBT delivery
techniques, single-shield RSBT (S-RSBT) and dynamic-shield RSBT (D-RSBT), with a
properly selected paddle size. If the paddle size was angled at 60 degrees , the
average D90 increases for the delivery plans by P-RSBT on the five cases,
compared to S-RSBT, were 2.2, 8.3, 12.6, 11.9, and 9.1 Gy10, respectively, with
delivery times of 10, 15, 20, 25, and 30 min/fx. The increases in HR-CTV D90,
compared to D-RSBT, were 16.6, 12.9, 7.2, 3.7, and 1.7 Gy10, respectively. P-RSBT
HR-CTV D90-values were insensitive to the paddle size for paddles angled at less
than 60 degrees . Increasing the paddle angle from 5 degrees to 60 degrees
resulted in only a 0.6 Gy10 decrease in HR-CTV D90 on average for five cases when
the delivery times were set to 15 min/fx. The HR-CTV D90 decreased to 2.5 and
11.9 Gy10 with paddle angles of 90 degrees and 120 degrees , respectively.
CONCLUSIONS: P-RSBT produces treatment plans that are dosimetrically and
temporally superior to those of S-RSBT and D-RSBT, although P-RSBT systems may be
more mechanically challenging to develop than S-RSBT or D-RSBT. A P-RSBT
implementation with 4-6 shield paddles would be sufficient to outperform S-RSBT
and D-RSBT if delivery times are constrained to less than 15 min/fx.
PMID- 26429275
TI - Factors that may determine the targeting accuracy of image-guided radiosurgery.
AB - PURPOSE: The AAPM TG-135 report is a landmark recommendation for the quality
assurance (QA) of image-guided robotic radiosurgery. The purpose of this paper is
to present results pertaining to intentionally offsetting the phantom as
recommended by TG-135 and to present data on targeting algorithm accuracy as a
function of imager parameters in less than ideal circumstances, which had not
been available at the time of publication of TG-135. METHODS: All tests in this
study were performed at the Cooper University Hospital CyberKnife Center in Mt.
Laurel, NJ. For intentional offsets, initial tests were performed on the Accuray
supplied anthropomorphic head and neck phantom, whereas for subsequent tests, the
Accuray-supplied alignment quality assurance (AQA) phantom was used. To simulate
the effects of imager parameters for larger patients, slabs of Blue Water
(Standard Imaging, Inc., Middleton, WI) were added to attenuate the x-ray images
in some of the tests. In conjunction with attenuated x-ray tests, the number of
fiducials was varied by systematically deselecting them one at a time at the
CyberKnife console. RESULTS: Tests using the AQA phantom verified that
submillimeter alignments were consistently achieved even with intentional shifts
and rotations of up to 10.0 mm and 1.0 degrees , respectively. An analysis of 17
months of daily QA alignment tests showed that submillimeter alignments were
achieved more than 99% of the time even with such intentional shifts and
rotations of the phantom. When additional slabs of Blue Water were added to
simulate patient attenuation of the x-ray images, targeting errors could be
induced depending on imager parameters and the amount of Blue Water used. A
series of consecutive tests showed that two helpful variables to ensure good
accuracy of the system were (1) the fiducial extraction confidence level (FECL)
system parameter and (2) the number of targeted fiducials. When fewer than four
fiducials were used, the FECL reported by the CyberKnife was sometimes high even
when a false lock occurred, so using multiple fiducials helped to ensure reliable
targeting. CONCLUSIONS: Radiosurgery requires the highest degree of targeting
accuracy, and in our experience, the CyberKnife has been able to maintain
submillimeter accuracy consistently. It has been verified that our CyberKnife can
correct for phantom shifts of up to 10.0 mm and rotations of up to 1.0 degrees .
It has also been discovered that false locks are more likely to occur with a
single fiducial than with multiple fiducials. Although targeting accuracy can
only be measured on a phantom, the insight gained from analyzing the QA tests can
help us in devising better strategies for achieving the best treatment for our
patients.
PMID- 26429276
TI - The influence of focal spot blooming on high-contrast spatial resolution in CT
imaging.
AB - PURPOSE: The objective of this work was to investigate focal spot blooming
effects on the spatial resolution of CT images and to evaluate an x-ray tube that
uses dynamic focal spot control for minimizing focal spot blooming. METHODS: The
influence of increasing tube current at a fixed tube potential of 80 kV on high
contrast spatial resolution of seven different CT scanner models (scanners A-G),
including one scanner that uses dynamic focal spot control to reduce focal spot
blooming (scanner A), was evaluated. Spatial resolution was assessed using a wire
phantom for the modulation transfer function (MTF) calculation and a copper disc
phantom for measuring the slice sensitivity profile (SSP). The impact of varying
the tube potential was investigated on two scanner models (scanners A and B) by
measuring the MTF and SSP and also by using the resolution bar pattern module of
the ACR CT phantom. The phantoms were scanned at 70-150 kV on scanner A and 80
140 kV on scanner B, with tube currents from 100 mA up to the maximum tube
current available on each scanner. The images were reconstructed using a slice
thickness of 0.6 mm with both smooth and sharp kernels. Additionally, focal spot
size at varying tube potentials and currents was directly measured using pinhole
and slit camera techniques. RESULTS: Evaluation of the MTF and SSP data from the
7 CT scanner models evaluated demonstrated decreased focal spot blooming for
newer scanners, as evidenced by decreasing deviations in MTF and SSP as tube
current varied. For scanners A and B, where focal spot blooming effects as a
function of tube potential were assessed, the spatial resolution variation in the
axial plane was much smaller on scanner A compared to scanner B as tube potential
and current changed. On scanner A, the 50% MTF never decreased by more than 2%
from the 50% MTF measured at 100 mA. On scanner B, the 50% MTF decreased by as
much as 19% from the 50% MTF measured at 100 mA. Assessments of the SSP, the bar
patterns in the ACR phantom and the pinhole and slit camera measurements were
consistent with the MTF calculations. CONCLUSIONS: Focal spot blooming has a
noticeable effect on spatial resolution in CT imaging. The focal spot shaping
technology of scanner A greatly reduced blooming effects.
PMID- 26429277
TI - A virtual simulator designed for collision prevention in proton therapy.
AB - PURPOSE: In proton therapy, collisions between the patient and nozzle potentially
occur because of the large nozzle structure and efforts to minimize the air gap.
Thus, software was developed to predict such collisions between the nozzle and
patient using treatment virtual simulation. METHODS: Three-dimensional (3D)
modeling of a gantry inner-floor, nozzle, and robotic-couch was performed using
SolidWorks based on the manufacturer's machine data. To obtain patient body
information, a 3D-scanner was utilized right before CT scanning. Using the
acquired images, a 3D-image of the patient's body contour was reconstructed. The
accuracy of the image was confirmed against the CT image of a humanoid phantom.
The machine components and the virtual patient were combined on the treatment
room coordinate system, resulting in a virtual simulator. The simulator simulated
the motion of its components such as rotation and translation of the gantry,
nozzle, and couch in real scale. A collision, if any, was examined both in static
and dynamic modes. The static mode assessed collisions only at fixed positions of
the machine's components, while the dynamic mode operated any time a component
was in motion. A collision was identified if any voxels of two components, e.g.,
the nozzle and the patient or couch, overlapped when calculating volume
locations. The event and collision point were visualized, and collision volumes
were reported. RESULTS: All components were successfully assembled, and the
motions were accurately controlled. The 3D-shape of the phantom agreed with CT
images within a deviation of 2 mm. Collision situations were simulated within
minutes, and the results were displayed and reported. CONCLUSIONS: The developed
software will be useful in improving patient safety and clinical efficiency of
proton therapy.
PMID- 26429278
TI - Radiobiologically optimized couch shift: A new localization paradigm using cone
beam CT for prostate radiotherapy.
AB - PURPOSE: To present a novel positioning strategy which optimizes radiation
delivery by utilizing radiobiological response knowledge and evaluate its use
during prostate external beam radiotherapy. METHODS: Five patients with low or
intermediate risk prostate cancer were evaluated retrospectively in this IRB
approved study. For each patient, a VMAT plan with one 358 degrees arc was
generated on the planning CT (PCT) to deliver 78 Gy in 39 fractions. Five
representative pretreatment cone beam CTs (CBCT) were selected for each patient.
The CBCT images were registered to PCT by a human observer, which consisted of an
initial automated registration with three degrees-of-freedom, followed by manual
adjustment for agreement at the prostate/rectal wall interface. To determine the
optimal treatment position for each CBCT, a search was performed centering on the
observer-matched position (OM-position) utilizing a score function based on
radiobiological and dosimetric indices (EUDprostate, D99prostate, NTCPrectum, and
NTCPbladder) for the prostate, rectum, and bladder. We termed the optimal
treatment position the radiobiologically optimized couch shift position (ROCS
position). RESULTS: The dosimetric indices, averaged over the five patients'
treatment plans, were (mean +/- SD) 79.5 +/- 0.3 Gy (EUDprostate), 78.2 +/- 0.4
Gy (D99prostate), 11.1% +/- 2.7% (NTCPrectum), and 46.9% +/- 7.6% (NTCPbladder).
The corresponding values from CBCT at the OM-positions were 79.5 +/- 0.6 Gy
(EUDprostate), 77.8 +/- 0.7 Gy (D99prostate), 12.1% +/- 5.6% (NTCPrectum), and
51.6% +/- 15.2% (NTCPbladder), respectively. In comparison, from CBCT at the ROCS
positions, the dosimetric indices were 79.5 +/- 0.6 Gy (EUDprostate), 77.3 +/-
0.6 Gy (D99prostate), 8.0% +/- 3.3% (NTCPrectum), and 46.9% +/- 15.7%
(NTCPbladder). Excessive NTCPrectum was observed on Patient 5 (19.5% +/- 6.6%)
corresponding to localization at OM-position, compared to the planned value of
11.7%. This was mitigated with radiobiologically optimized localization,
resulting in a reduced NTCPrectum value of 11.3% +/- 3.5%. Overall, the treatment
position optimization resulted in similar target dose coverage with reduced risk
to rectum. CONCLUSIONS: These encouraging results illustrate the potential
advantage of applying radiobiologically optimized correction for online image
guided radiotherapy of prostate patients.
PMID- 26429279
TI - Detector dose response in megavoltage small photon beams. I. Theoretical
concepts.
AB - PURPOSE: To explain the reasons for significant quality correction factors in
megavoltage small photon fields and clarify the underlying concepts relevant to
dosimetry under such conditions. METHODS: The validity of cavity theory and the
requirement of charged particle equilibrium (CPE) are addressed from a
theoretical point of view in the context of nonstandard beams. Perturbation
effects are described into four main subeffects, explaining their nature and
pointing out their relative importance in small photon fields. RESULTS: It is
demonstrated that the failure to meet classical cavity theory requirements, such
as CPE, is not the reason for significant quality correction factors. On the
contrary, it is shown that the lack of CPE alone cannot explain these corrections
and that what matters most, apart from volume averaging effects, is the
relationship between the lack of CPE in the small field itself and the density of
the detector cavity. The density perturbation effect is explained based on Fano's
theorem, describing the compensating effect of two main contributions to cavity
absorbed dose. Using the same approach, perturbation effects arising from the
difference in atomic properties of the cavity medium and the presence of
extracameral components are explained. Volume averaging effects are also
discussed in detail. CONCLUSIONS: Quality correction factors of small megavoltage
photon fields are mainly due to differences in electron density between water and
the detector medium and to volume averaging over the detector cavity. Other
effects, such as the presence of extracameral components and differences in
atomic properties of the detection medium with respect to water, can also play an
accentuated role in small photon fields compared to standard beams.
PMID- 26429280
TI - Detector dose response in megavoltage small photon beams. II. Pencil beam
perturbation effects.
AB - PURPOSE: To quantify detector perturbation effects in megavoltage small photon
fields and support the theoretical explanation on the nature of quality
correction factors in these conditions. METHODS: In this second paper, a modern
approach to radiation dosimetry is defined for any detector and applied to small
photon fields. Fano's theorem is adapted in the form of a cavity theory and
applied in the context of nonstandard beams to express four main effects in the
form of perturbation factors. The pencil-beam decomposition method is detailed
and adapted to the calculation of perturbation factors and quality correction
factors. The approach defines a perturbation function which, for a given field
size or beam modulation, entirely determines these dosimetric factors. Monte
Carlo calculations are performed in different cavity sizes for different
detection materials, electron densities, and extracameral components. RESULTS:
Perturbation effects are detailed with calculated perturbation functions, showing
the relative magnitude of the effects as well as the geometrical extent to which
collimating or modulating the beam impacts the dosimetric factors. The existence
of a perturbation zone around the detector cavity is demonstrated and the
approach is discussed and linked to previous approaches in the literature to
determine critical field sizes. CONCLUSIONS: Monte Carlo simulations are valuable
to describe pencil beam perturbation effects and detail the nature of dosimetric
factors in megavoltage small photon fields. In practice, it is shown that
dosimetric factors could be avoided if the field size remains larger than the
detector perturbation zone. However, given a detector and beam quality, a full
account for the detector geometry is necessary to determine critical field sizes.
PMID- 26429281
TI - Analytic reconstruction algorithms for triple-source CT with horizontal data
truncation.
AB - PURPOSE: This paper explores a triple-source imaging method with horizontal data
truncation to enlarge the field of view (FOV) for big objects. METHODS: The study
is conducted by using theoretical analysis, mathematical deduction, and numerical
simulations. The proposed algorithms are implemented in c + + and matlab. While
the basic platform is constructed in matlab, the computationally intensive
segments are coded in c + +, which are linked via a mex interface. RESULTS: A
triple-source circular scanning configuration with horizontal data truncation is
developed, where three pairs of x-ray sources and detectors are unevenly
distributed on the same circle to cover the whole imaging object. For this triple
source configuration, a fan-beam filtered backprojection-type algorithm is
derived for truncated full-scan projections without data rebinning. The algorithm
is also extended for horizontally truncated half-scan projections and cone-beam
projections in a Feldkamp-type framework. Using their method, the FOV is enlarged
twofold to threefold to scan bigger objects with high speed and quality. The
numerical simulation results confirm the correctness and effectiveness of the
developed algorithms. CONCLUSIONS: The triple-source scanning configuration with
horizontal data truncation cannot only keep most of the advantages of a
traditional multisource system but also cover a larger FOV for big imaging
objects. In addition, because the filtering is shift-invariant, the proposed
algorithms are very fast and easily parallelized on graphic processing units.
PMID- 26429282
TI - Automating linear accelerator quality assurance.
AB - PURPOSE: The purpose of this study was 2-fold. One purpose was to develop an
automated, streamlined quality assurance (QA) program for use by multiple
centers. The second purpose was to evaluate machine performance over time for
multiple centers using linear accelerator (Linac) log files and electronic portal
images. The authors sought to evaluate variations in Linac performance to
establish as a reference for other centers. METHODS: The authors developed
analytical software tools for a QA program using both log files and electronic
portal imaging device (EPID) measurements. The first tool is a general analysis
tool which can read and visually represent data in the log file. This tool, which
can be used to automatically analyze patient treatment or QA log files, examines
the files for Linac deviations which exceed thresholds. The second set of tools
consists of a test suite of QA fields, a standard phantom, and software to
collect information from the log files on deviations from the expected values.
The test suite was designed to focus on the mechanical tests of the Linac to
include jaw, MLC, and collimator positions during static, IMRT, and volumetric
modulated arc therapy delivery. A consortium of eight institutions delivered the
test suite at monthly or weekly intervals on each Linac using a standard phantom.
The behavior of various components was analyzed for eight TrueBeam Linacs.
RESULTS: For the EPID and trajectory log file analysis, all observed deviations
which exceeded established thresholds for Linac behavior resulted in a beam hold
off. In the absence of an interlock-triggering event, the maximum observed log
file deviations between the expected and actual component positions (such as MLC
leaves) varied from less than 1% to 26% of published tolerance thresholds. The
maximum and standard deviations of the variations due to gantry sag, collimator
angle, jaw position, and MLC positions are presented. Gantry sag among Linacs was
0.336 +/- 0.072 mm. The standard deviation in MLC position, as determined by EPID
measurements, across the consortium was 0.33 mm for IMRT fields. With respect to
the log files, the deviations between expected and actual positions for
parameters were small (<0.12 mm) for all Linacs. Considering both log files and
EPID measurements, all parameters were well within published tolerance values.
Variations in collimator angle, MLC position, and gantry sag were also evaluated
for all Linacs. CONCLUSIONS: The performance of the TrueBeam Linac model was
shown to be consistent based on automated analysis of trajectory log files and
EPID images acquired during delivery of a standardized test suite. The results
can be compared directly to tolerance thresholds. In addition, sharing of results
from standard tests across institutions can facilitate the identification of QA
process and Linac changes. These reference values are presented along with the
standard deviation for common tests so that the test suite can be used by other
centers to evaluate their Linac performance against those in this consortium.
PMID- 26429283
TI - Technical Note: Simulation of 4DCT tumor motion measurement errors.
AB - PURPOSE: To determine if and by how much the commercial 4DCT protocols under- and
overestimate tumor breathing motion. METHODS: 1D simulations were conducted that
modeled a 16-slice CT scanner and tumors moving proportionally to breathing
amplitude. External breathing surrogate traces of at least 5-min duration for 50
patients were used. Breathing trace amplitudes were converted to motion by
relating the nominal tumor motion to the 90th percentile breathing amplitude,
reflecting motion defined by the more recent 5DCT approach. Based on clinical low
pitch helical CT acquisition, the CT detector moved according to its velocity
while the tumor moved according to the breathing trace. When the CT scanner
overlapped the tumor, the overlapping slices were identified as having imaged the
tumor. This process was repeated starting at successive 0.1 s time bin in the
breathing trace until there was insufficient breathing trace to complete the
simulation. The tumor size was subtracted from the distance between the most
superior and inferior tumor positions to determine the measured tumor motion for
that specific simulation. The effect of the scanning parameter variation was
evaluated using two commercial 4DCT protocols with different pitch values.
Because clinical 4DCT scan sessions would yield a single tumor motion
displacement measurement for each patient, errors in the tumor motion measurement
were considered systematic. The mean of largest 5% and smallest 5% of the
measured motions was selected to identify over- and underdetermined motion
amplitudes, respectively. The process was repeated for tumor motions of 1-4 cm in
1 cm increments and for tumor sizes of 1-4 cm in 1 cm increments. RESULTS: In the
examined patient cohort, simulation using pitch of 0.06 showed that 30% of the
patients exhibited a 5% chance of mean breathing amplitude overestimations of
47%, while 30% showed a 5% chance of mean breathing amplitude underestimations of
36%; with a separate simulation using pitch of 0.1 showing, respectively, 37%
overestimation and 61% underestimation. CONCLUSIONS: The simulation indicates
that commercial low-pitch helical 4DCT processes potentially yield large tumor
motion measurement errors, both over- and underestimating the tumor motion.
PMID- 26429284
TI - Technical Note: MRI only prostate radiotherapy planning using the statistical
decomposition algorithm.
AB - PURPOSE: In order to enable a magnetic resonance imaging (MRI) only workflow in
radiotherapy treatment planning, methods are required for generating Hounsfield
unit (HU) maps (i.e., synthetic computed tomography, sCT) for dose calculations,
directly from MRI. The Statistical Decomposition Algorithm (SDA) is a method for
automatically generating sCT images from a single MR image volume, based on
automatic tissue classification in combination with a model trained using a
multimodal template material. This study compares dose calculations between sCT
generated by the SDA and conventional CT in the male pelvic region. METHODS: The
study comprised ten prostate cancer patients, for whom a 3D T2 weighted MRI and a
conventional planning CT were acquired. For each patient, sCT images were
generated from the acquired MRI using the SDA. In order to decouple the effect of
variations in patient geometry between imaging modalities from the effect of
uncertainties in the SDA, the conventional CT was nonrigidly registered to the
MRI to assure that their geometries were well aligned. For each patient, a
volumetric modulated arc therapy plan was created for the registered CT (rCT) and
recalculated for both the sCT and the conventional CT. The results were evaluated
using several methods, including mean average error (MAE), a set of dose-volume
histogram parameters, and a restrictive gamma criterion (2% local dose/1 mm).
RESULTS: The MAE within the body contour was 36.5 +/- 4.1 (1 s.d.) HU between sCT
and rCT. Average mean absorbed dose difference to target was 0.0% +/- 0.2% (1
s.d.) between sCT and rCT, whereas it was -0.3% +/- 0.3% (1 s.d.) between CT and
rCT. The average gamma pass rate was 99.9% for sCT vs rCT, whereas it was 90.3%
for CT vs rCT. CONCLUSIONS: The SDA enables a highly accurate MRI only workflow
in prostate radiotherapy planning. The dosimetric uncertainties originating from
the SDA appear negligible and are notably lower than the uncertainties introduced
by variations in patient geometry between imaging sessions.
PMID- 26429286
TI - 3D localization of electrophysiology catheters from a single x-ray cone-beam
projection.
AB - PURPOSE: X-ray images allow the visualization of percutaneous devices such as
catheters in real time but inherently lack depth information. The provision of 3D
localization of these devices from cone beam x-ray projections would be
advantageous for interventions such as electrophysiology (EP), whereby the
operator needs to return a device to the same anatomical locations during the
procedure. A method to achieve real-time 3D single view localization (SVL) of an
object of known geometry from a single x-ray image is presented. svl exploits the
change in the magnification of an object as its distance from the x-ray source is
varied. The x-ray projection of an object of interest is compared to a synthetic
x-ray projection of a model of said object as its pose is varied. METHODS: svl
was tested with a 3 mm spherical marker and an electrophysiology catheter. The
effect of x-ray acquisition parameters on svl was investigated. An independent
reference localization method was developed to compare results when imaging a
catheter translated via a computer controlled three-axes stage. svl was also
performed on clinical fluoroscopy image sequences. A commercial navigation system
was used in some clinical image sequences for comparison. RESULTS: svl estimates
exhibited little change as x-ray acquisition parameters were varied. The
reproducibility of catheter position estimates in phantoms denoted by the
standard deviations, (sigma(x), sigma(y), sigma(z)) = (0.099 mm, 0.093 mm, 2.2
mm), where x and y are parallel to the detector plane and z is the distance from
the x-ray source. Position estimates (x, y, z) exhibited a 4% systematic error
(underestimation) when compared to the reference method. The authors demonstrated
that EP catheters can be tracked in clinical fluoroscopic images. CONCLUSIONS: It
has been shown that EP catheters can be localized in real time in phantoms and
clinical images at fluoroscopic exposure rates. Further work is required to
characterize performance in clinical images as well as the sensitivity to
clinical image quality.
PMID- 26429285
TI - Computational and human observer image quality evaluation of low dose, knowledge
based CT iterative reconstruction.
AB - PURPOSE: Aims in this study are to (1) develop a computational model observer
which reliably tracks the detectability of human observers in low dose computed
tomography (CT) images reconstructed with knowledge-based iterative
reconstruction (IMRTM, Philips Healthcare) and filtered back projection (FBP)
across a range of independent variables, (2) use the model to evaluate
detectability trends across reconstructions and make predictions of human
observer detectability, and (3) perform human observer studies based on model
predictions to demonstrate applications of the model in CT imaging. METHODS:
Detectability (d') was evaluated in phantom studies across a range of conditions.
Images were generated using a numerical CT simulator. Trained observers performed
4-alternative forced choice (4-AFC) experiments across dose (1.3, 2.7, 4.0 mGy),
pin size (4, 6, 8 mm), contrast (0.3%, 0.5%, 1.0%), and reconstruction (FBP,
IMR), at fixed display window. A five-channel Laguerre-Gauss channelized
Hotelling observer (CHO) was developed with internal noise added to the decision
variable and/or to channel outputs, creating six different internal noise models.
Semianalytic internal noise computation was tested against Monte Carlo and used
to accelerate internal noise parameter optimization. Model parameters were
estimated from all experiments at once using maximum likelihood on the
probability correct, PC. Akaike information criterion (AIC) was used to compare
models of different orders. The best model was selected according to AIC and used
to predict detectability in blended FBP-IMR images, analyze trends in IMR
detectability improvements, and predict dose savings with IMR. Predicted dose
savings were compared against 4-AFC study results using physical CT phantom
images. RESULTS: Detection in IMR was greater than FBP in all tested conditions.
The CHO with internal noise proportional to channel output standard deviations,
Model-k4, showed the best trade-off between fit and model complexity according to
AICc. With parameters fixed, the model reasonably predicted detectability of
human observers in blended FBP-IMR images. Semianalytic internal noise
computation gave results equivalent to Monte Carlo, greatly speeding parameter
estimation. Using Model-k4, the authors found an average detectability
improvement of 2.7 +/- 0.4 times that of FBP. IMR showed greater improvements in
detectability with larger signals and relatively consistent improvements across
signal contrast and x-ray dose. In the phantom tested, Model-k4 predicted an 82%
dose reduction compared to FBP, verified with physical CT scans at 80% reduced
dose. CONCLUSIONS: IMR improves detectability over FBP and may enable significant
dose reductions. A channelized Hotelling observer with internal noise
proportional to channel output standard deviation agreed well with human
observers across a wide range of variables, even across reconstructions with
drastically different image characteristics. Utility of the model observer was
demonstrated by predicting the effect of image processing (blending), analyzing
detectability improvements with IMR across dose, size, and contrast, and in
guiding real CT scan dose reduction experiments. Such a model observer can be
applied in optimizing parameters in advanced iterative reconstruction algorithms
as well as guiding dose reduction protocols in physical CT experiments.
PMID- 26429288
TI - Hormone Replacement Therapy and Risk of Breast Cancer in Korean Women: A
Quantitative Systematic Review.
AB - OBJECTIVES: The epidemiological characteristics of breast cancer incidence by age
group in Korean women are unique. This systematic review aimed to investigate the
association between hormone replacement therapy (HRT) and breast cancer risk in
Korean women. METHODS: We searched electronic databases such as KoreaMed, KMbase,
KISS, and RISS4U as well as PubMed for publications on Korean breast cancer
patients. We also conducted manual searching based on references and citations in
potential papers. All of the analytically epidemiologic studies that obtained
individual data on HRT exposure and breast cancer occurrence in Korean women were
selected. We restricted the inclusion of case-control studies to those that
included age-matched controls. Estimates of summary odds ratio (SOR) with 95%
confidence intervals (CIs) were calculated using random effect models. RESULTS:
One cohort and five case-control studies were finally selected. Based on the
heterogeneity that existed among the six studies (I-squared=70.2%), a random
effect model was applied. The summary effect size of HRT history from the six
articles indicated no statistical significance in breast cancer risk (SOR, 0.983;
95% CI, 0.620 to 1.556). CONCLUSIONS: These facts support no significant effect
of HRT history in the risk of breast cancer in Korean women. It is necessary to
conduct a pooled analysis.
PMID- 26429289
TI - A Study of Predictive Factors Affecting Health: Promoting Behaviors of North
Korean Adolescent Refugees.
AB - OBJECTIVES: The present study aimed to analyze the factors that could affect the
health-promoting behaviors of North Korean adolescent refugees residing in South
Korea. METHODS: Questions about their sociodemographic variables, subjective
health status, healthy living habits, and health-promoting behaviors were asked.
RESULTS: Statistically significant differences were found in religion (t=2.30,
p<0.05), having family members in South Korea (t=2.02, p<0.05), and subjective
health status (t=4.96, p<0.01). Scores on health-responsible behaviors were
higher with higher age (t=2.90, p<0.01) and for subjects without family or
friends (t=2.43, p<0.05). Higher physical-activity behaviors were observed in
males (t=3.32, p<0.01), in those with better subjective health status (t=3.46,
p<0.05) and lower body mas index (t=3.48, p<0.05), and in smokers (t=3.17,
p<0.01). Nutritional behaviors were higher in those who followed a religion
(t=2.17, p<0.05). Spiritual growth behaviors were higher in those who followed a
religion (t=4.21, p<0.001), had no family in South Korea (t=2.04, p<0.05), and
had higher subjective health status (t=5.74, p<0.01). Scores on interpersonal
relationships and stress-management behaviors were higher for those with higher
subjective health status. A multiple regression analysis showed greater effects
on health-promoting behaviors when subjective health status was better. Older
people and non-smokers exhibited more health-responsible behaviors, while more
physical-activity behaviors and spiritual growth activities were observed when
subjective health status was better. Interpersonal relationship behaviors had
positive effects on those with good subjective heath status and on non-smokers.
CONCLUSIONS: Based on the results of the current study, an alternative was
suggested for promoting health in North Korean adolescent refugees.
PMID- 26429290
TI - Assessing Reliability of Medical Record Reviews for the Detection of Hospital
Adverse Events.
AB - OBJECTIVES: The purpose of this study was to assess the inter-rater reliability
and intra-rater reliability of medical record review for the detection of
hospital adverse events. METHODS: We conducted two stages retrospective medical
records review of a random sample of 96 patients from one acute-care general
hospital. The first stage was an explicit patient record review by two nurses to
detect the presence of 41 screening criteria (SC). The second stage was an
implicit structured review by two physicians to identify the occurrence of
adverse events from the positive cases on the SC. The inter-rater reliability of
two nurses and that of two physicians were assessed. The intra-rater reliability
was also evaluated by using test-retest method at approximately two weeks later.
RESULTS: In 84.2% of the patient medical records, the nurses agreed as to the
necessity for the second stage review (kappa, 0.68; 95% confidence interval [CI],
0.54 to 0.83). In 93.0% of the patient medical records screened by nurses, the
physicians agreed about the absence or presence of adverse events (kappa, 0.71;
95% CI, 0.44 to 0.97). When assessing intra-rater reliability, the kappa indices
of two nurses were 0.54 (95% CI, 0.31 to 0.77) and 0.67 (95% CI, 0.47 to 0.87),
whereas those of two physicians were 0.87 (95% CI, 0.62 to 1.00) and 0.37 (95%
CI, -0.16 to 0.89). CONCLUSIONS: In this study, the medical record review for
detecting adverse events showed intermediate to good level of inter-rater and
intra-rater reliability. Well organized training program for reviewers and
clearly defining SC are required to get more reliable results in the hospital
adverse event study.
PMID- 26429291
TI - Interaction of Vitamin D and Smoking on Inflammatory Markers in the Urban
Elderly.
AB - OBJECTIVES: Epidemiological studies have reported that vitamin D deficiency is
associated with inflammatory disease. Smoking is a well-known risk factor for
inflammation. However, few studies have investigated the interactive effect of
vitamin D deficiency and smoking on inflammation. This study aims to investigate
the interaction of vitamin D and smoking with inflammatory markers in the urban
elderly. METHODS: We used data from the Korean Elderly Environmental Panel Study,
which began in August 2008 and ended in August 2010, and included 560 Koreans
>=60 years old living in Seoul. Data was collected via questionnaires that
included items about smoking status at the first visit. Vitamin D levels, high
sensitivity C-reactive protein (hs-CRP), and white blood cell (WBC) counts were
repeatedly measured up to three times. RESULTS: The association of vitamin D and
hs-CRP was significant after adjusting for known confounders (beta=-0.080,
p=0.041). After separate analysis by smoking status, the association of vitamin D
deficiency and hs-CRP in smokers was stronger than that in nonsmokers (smokers:
beta=-0.375, p=0.013; non-smokers: beta=-0.060, p=0.150). Smoking status was an
effect modifier that changed the association between vitamin D deficiency and hs
CRP (interaction estimate: beta=-0.254, p=0.032). Vitamin D was not significantly
associated with WBC count (beta=0.003, p=0.805). CONCLUSIONS: Vitamin D
deficiency was associated with hs-CRP in the urban elderly. Smoking status was an
effect modifier of this association. Vitamin D deficiency was not significantly
associated with WBC count.
PMID- 26429292
TI - Prevalence of Depressive Disorder of Outpatients Visiting Two Primary Care
Settings.
AB - OBJECTIVES: Although the prevalence of depressive disorders in South Korea's
general population is known, no reports on the prevalence of depression among
patients who visit primary care facilities have been published. This preliminary
study was conducted to identify the prevalence of depressive disorder in patients
that visit two primary care facilities. METHODS: Among 231 consecutive eligible
patients who visited two primary care settings, 184 patients consented to a
diagnostic interview for depression by psychiatrists following the Diagnostic and
Statistical Manual of Mental Disorders-IV criteria. There were no significant
differences in sociodemographic characteristics such as gender, age, or level of
education between the groups that consented and declined the diagnostic
examination. The prevalence of depressive disorder and the proportion of newly
diagnosed patients among depressive disorder patients were calculated. RESULTS:
The prevalence of depressive disorder of patients in the two primary care
facilities was 14.1% (95% confidence interval [CI], 9.1 to 19.2), with major
depressive disorder 5.4% (95% CI, 2.1 to 8.7), dysthymia 1.1% (95% CI, 0.0 to
2.6), and depressive disorder, not otherwise specified 7.6% (95% CI, 3.7 to
11.5). Among the 26 patients with depressive disorder, 19 patients were newly
diagnosed. CONCLUSIONS: As compared to the general population, a higher
prevalence of depressive disorders was observed among patients at two primary
care facilities. Further study is needed with larger samples to inform the
development of a primary care setting-based depression screening, management, and
referral system to increase the efficiency of limited health care resources.
PMID- 26429293
TI - Candida lusitaniae MICs to the echinocandins are elevated but FKS-mediated
resistance is rare.
AB - MIC values were generated for caspofungin, micafungin, and anidulafungin against
106 isolates of C. lusitaniae, and these values were compared to established
epidemiologic cutoff values. The majority of isolates were wild type both by MIC
value as well as by FKS1 hotspot sequencing. Although C. lusitaniae isolates have
MIC values to the echinocandins that are elevated compared to other common
species, with regard to known mechanisms of resistance to the echinocandins,
isolates with MIC values at or below the epidemiological cutoff values of 0.5 and
1 MUg/mL for micafungin and anidulafungin, respectively, should be considered
wild type.
PMID- 26429294
TI - Correlation between genetic features of the mef(A)-msr(D) locus and erythromycin
resistance in Streptococcus pyogenes.
AB - We investigated the correlation between the genetic variation within mef(A)
msr(D) determinants of efflux-mediated erythromycin resistance in Streptococcus
pyogenes and the level of erythromycin resistance. Twenty-eight mef(A)-positive
strains were selected according to erythromycin MIC (4-32 MUg/mL), and their
mef(A)-msr(D) regions were sequenced. Strains were classified according to the
bacteriophage carrying mef(A)-msr(D). A new Phim46.1 genetic variant was found in
8 strains out of 28 and named VP_00501.1. Degree of allelic variation was higher
in mef(A) than in msr(D). Hotspots for recombination were mapped within the locus
that could have shaped the apparent mosaic structure of the region. There was a
general correlation between mef(A)-msr(D) sequence and erythromycin resistance
level. However, lysogenic conversion of susceptible strains by mef(A)-msr(D)
carrying Phim46.1 indicated that key determinants may not all reside within the
mef(A)-msr(D) locus and that horizontal gene transfer could contribute to changes
in the level of antibiotic resistance in S. pyogenes.
PMID- 26429295
TI - Correlation of Organic Cation/Carnitine Transporter 1 and Multidrug Resistance
Associated Protein 1 Transport Activities With Protein Expression Levels in
Primary Cultured Human Tracheal, Bronchial, and Alveolar Epithelial Cells.
AB - Understanding how transporters contribute to the distribution of inhaled drugs in
the lung is important for the discovery and development of such drugs. Protein
expression levels may be useful to predict and understand drug distribution. As
previously reported, organic cation/carnitine transporter 1 (OCTN1) and multidrug
resistance-associated protein 1 (MRP1) have higher levels of protein expression
among transporters in primary cultured human lung cells. Nevertheless, it is
unclear to what extent transport activity correlates with transporter protein
expression. The purpose is to evaluate whether differences in OCTN1 and MRP1
protein expression govern the respective transport activity in primary cultured
human lung cells. The model substrates of 4-[4-(dimethylamino) styryl]-N
methylpyridinium iodide (ASP(+)) and carboxy-dichlorofluorescein (CDF) for OCTN1
and MRP1, respectively, were used in the lung cells from five donors. Significant
correlation was found between the kinetic parameter Vmax for ASP(+) and OCTN1
protein expression in plasma membrane of tracheal, bronchial, and alveolar cells
(r(2) = 0.965, 0.834, and 0.877, respectively), and between the efflux of CDF and
MRP1 protein expression in plasma membrane of tracheal, bronchial, and alveolar
cells (r(2) = 0.800, 0.904, and 0.790, respectively). These findings suggest that
OCTN1 and MRP1 protein concentrations are determinants for drug distribution in
the lung.
PMID- 26429296
TI - The relationship between quantitative human epidermal growth factor receptor 2
gene expression by the 21-gene reverse transcriptase polymerase chain reaction
assay and adjuvant trastuzumab benefit in Alliance N9831.
AB - INTRODUCTION: The N9831 trial demonstrated the efficacy of adjuvant trastuzumab
for patients with human epidermal growth factor receptor 2 (HER2) locally
positive tumors by protein or gene analysis. We used the 21-gene assay to examine
the association of quantitative HER2 messenger RNA (mRNA) gene expression and
benefit from trastuzumab. METHODS: N9831 tested the addition of trastuzumab to
chemotherapy in stage I-III HER2-positive breast cancer. For two of the arms of
the trial, doxorubicin and cyclophosphamide followed by paclitaxel (AC-T) and
doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab
concurrent chemotherapy-trastuzumab (AC-TH), recurrence score (RS) and HER2 mRNA
expression were determined by the 21-gene assay (Oncotype DX(r)) (negative <10.7,
equivocal 10.7 to <11.5, and positive >=11.5 log2 expression units). Cox
regression was used to assess the association of HER2 expression with trastuzumab
benefit in preventing distant recurrence. RESULTS: Median follow-up was 7.4
years. Of 1,940 total patients, 901 had consent and sufficient tissue. HER2 by
reverse transcriptase polymerase chain reaction (RT-PCR) was negative in 130 (14
%), equivocal in 85 (9 %), and positive in 686 (76 %) patients. Concordance
between HER2 assessments was 95 % for RT-PCR versus central immunohistochemistry
(IHC) (>10 % positive cells = positive), 91 % for RT-PCR versus central
fluorescence in situ hybridization (FISH) (>=2.0 = positive) and 94 % for central
IHC versus central FISH. In the primary analysis, the association of HER2
expression by 21-gene assay with trastuzumab benefit was marginally
nonsignificant (nonlinear p = 0.057). In hormone receptor-positive patients
(local IHC) the association was significant (p = 0.002). The association was
nonlinear with the greatest estimated benefit at lower and higher HER2 expression
levels. CONCLUSIONS: Concordance among HER2 assessments by central IHC, FISH, and
RT-PCR were similar and high. Association of HER2 mRNA expression with
trastuzumab benefit as measured by time to distant recurrence was nonsignificant.
A consistent benefit of trastuzumab irrespective of mHER2 levels was observed in
patients with either IHC-positive or FISH-positive tumors. Trend for benefit was
observed also for the small groups of patients with negative results by any or
all of the central assays. TRIAL REGISTRATION: Clinicaltrials.gov NCT00005970 .
Registered 5 July 2000.
PMID- 26429298
TI - Expansion of chemical space for collaborative lead generation and drug discovery:
the European Lead Factory Perspective.
AB - High-throughput screening (HTS) represents a major cornerstone of drug discovery.
The availability of an innovative, relevant and high-quality compound collection
to be screened often dictates the final fate of a drug discovery campaign. Given
that the chemical space to be sampled in research programs is practically
infinite and sparsely populated, significant efforts and resources need to be
invested in the generation and maintenance of a competitive compound collection.
The European Lead Factory (ELF) project is addressing this challenge by
leveraging the diverse experience and know-how of academic groups and small and
medium enterprises (SMEs) engaged in synthetic and/or medicinal chemistry. Here,
we describe the novelty, diversity, structural complexity, physicochemical
characteristics and overall attractiveness of this first batch of ELF compounds
for HTS purposes.
PMID- 26429297
TI - Busulfan plus cyclophosphamide versus busulfan plus fludarabine as a preparative
regimen for allogeneic haemopoietic stem-cell transplantation in patients with
acute myeloid leukaemia: an open-label, multicentre, randomised, phase 3 trial.
AB - BACKGROUND: The standard busulfan-cyclophosphamide myeloablative conditioning
regimen is associated with substantial non-relapse mortality in patients older
than 40 years with acute myeloid leukaemia who are undergoing allogeneic stem
cell transplantation. Because the combination of busulfan plus fludarabine has
been proposed to reduce non-relapse mortality, we aimed to compare this treatment
with busulfan plus cyclophosphamide as a preparative regimen in these patients.
METHODS: We did an open-label, multicentre, randomised, phase 3 trial for
patients with acute myeloid leukaemia at 25 hospital transplant centres in Italy
and one in Israel. Eligible patients were aged 40-65 years, had an Eastern
Cooperative Oncology Group performance status less than 3, and were in complete
remission. Patients were randomly assigned 1:1 to receive intravenous busulfan
plus cyclophosphamide or busulfan plus fludarabine. Treatment allocations were
not masked to investigators or patients. Randomisation was done centrally via a
dedicated web-based system using remote data entry, with patients stratified by
donor type and complete remission status. Patients allocated to busulfan plus
cyclophosphamide received intravenous busulfan 0.8 mg/kg four times per day
during 2 h infusions for four consecutive days (16 doses from days -9 through -6;
total dose 12.8 mg/kg) and cyclophosphamide at 60 mg/kg per day for two
consecutive days (on days -4 and -3; total dose 120 mg/kg). Patients allocated to
busulfan plus fludarabine received the same dose of intravenous busulfan (from
days -6 through -3) and fludarabine at 40 mg/m(2) per day for four consecutive
days (from days -6 through -3; total dose 160 mg/m(2)). The primary endpoint was
1-year non-relapse mortality, which was assessed on an intention-to-treat basis;
safety outcomes were assessed in the per-protocol population. This trial has been
completed and is registered with ClinicalTrials.gov, number NCT01191957.
FINDINGS: Between Jan 3, 2008, and Dec 20, 2012, we enrolled and randomly
assigned 252 patients to receive busulfan plus cyclophosphamide (n=125) or
busulfan plus fludarabine (n=127). Median follow-up was 27.5 months (IQR 9.8
44.3). 1-year non-relapse mortality was 17.2% (95% CI 11.6-25.4) in the busulfan
plus cyclophosphamide group and 7.9% (4.3-14.3) in the busulfan plus fludarabine
group (Gray's test p=0.026). The most frequently reported grade 3 or higher
adverse events were gastrointestinal events (28 [23%] of 121 patients in the
busulfan plus cyclophosphamide group and 26 [21%] of 124 patients in the busulfan
plus fludarabine group) and infections (21 [17%] patients in the busulfan plus
cyclophosphamide group and 13 [10%] patients in the busulfan plus fludarabine
group had at least one such event). INTERPRETATION: In older patients with acute
myeloid leukaemia, the myeloablative busulfan plus fludarabine conditioning
regimen is associated with lower transplant-related mortality than busulfan plus
cyclophosphamide, but retains potent antileukaemic activity. Accordingly, this
regimen should be regarded as standard of care during the planning of allogeneic
transplants for such patients. FUNDING: Agenzia Italiana del Farmaco.
PMID- 26429299
TI - Expression levels of heat shock protein 60 and glucose-regulated protein 78 in
response to trimethylamine-N-oxide treatment in murine macrophage J774A.1 cell
line.
AB - Trimethylamine N-oxide (TMAO), a common metabolite in animals and humans, can
induce changes in the expression or conformation of heat shock proteins. It has
also been introduced as a risk factor for atherosclerosis and a biomarker for
kidney problems. On the other hand, increased levels of heat shock proteins 60
and 70 KDa are associated with increased atherosclerosis risk. This study was
therefore designed to evaluate the possible effect(s) of TMAO on the expression
of HSP60 and GRP78 at the mRNA and protein levels. Murine macrophage J774A.1
cells were treated with micromolar concentrations of TMAO and 4-phenylbutyric
acid (4-PBA), a chemical chaperon, for different time intervals. Tunicamycin was
also used as a control for induction of endoplasmic reticulum stress. Tunicamycin
greatly increased both mRNA and protein levels of GRP78. Similarly but to a
lesser extent compared to tunicamycin, TMAO also increased mRNA and protein
levels of GRP78 in a dose and time-dependent manner. In contrast, 4-PBA failed to
induce any changes. Similar to GRP78, HSP60 was also increased only at mRNA level
in TMAO treated cells. 4-PBA also increased HSP60 mRNA levels, whereas,
tunicamycin did not show any effect on either protein or mRNA levels of HSP60.
Since both heat shock proteins are stress inducible and the elevation of GRP78 is
a hallmark for endoplasmic reticulum stress induction, it can be concluded that
TMAO may induce endoplasmic reticulum stress or may act through elevation of
these heat shock proteins.
PMID- 26429300
TI - Comparative phenotypic and genotypic discrimination of methicillin resistant and
susceptible Staphylococcus aureus in Egypt.
AB - The present study was designed to elucidate the phenotypic and genotypic
characterization of S. aureus isolates in Egypt. The antibiotic susceptibility
pattern of 133 identified S. aureus isolates revealed that over 70% of the
isolates were multi-drug resistant (MDR). Fifty MDR isolates were characterized
using antibiotyping and different molecular typing methods. Amplification of mecA
gene confirmed 30 strains as methicillin-resistant S. aureus (MRSA) and 20 as
methicillin-sensitive S. aureus (MSSA). Generally, 22 MRSA (73.33%) and ten MSSA
(50%) harbored Panton-Valentine leukocidin (pvl) gene with no statistically
significant difference (p=0.093). Staphylococcal cassette chromosome (SCC) mec
typing revealed that 48% of the typeable MRSA isolates possessed SCCmec type IV.
SCCmec and antimicrobial susceptibility typing signified the presence of
community-acquired (CA)-MRSA in Egypt. Surprisingly, all isolates of SCCmec types
I, II and III and 50% of both MRSA isolates of SCCmec types IV and V possessed
pvl gene. It was clear that staphylococcal protein A (spa) and coagulase (coa)
typing discriminated the isolates into eight different groups, whilst polymerase
chain reaction-restriction fragment length polymorphism (PCR-RFLP) of coagulase
gene yielded ten distinct RFLP banding patterns. This study presented the first
baseline information on the characterization of MRSA and MSSA in Egypt.
PMID- 26429301
TI - Production and purification of novel thermostable alkaline protease from
Anoxybacillus sp. KP1.
AB - In this study, an extracellular novel alkaline protease (EC 3.4.21-24, 99) from a
thermophilic and aerobic strain of Anoxybacillus sp. KP1 has been studied.
Maximum protease activity was obtained at 50 degC at pH 9.0 after 24 hours of
incubation. Among the carbon and nitrogen sources used; the optimum protease
production was with soluble starch, maltose, urea and casamino acid. The enzyme
was purified by ammonium sulphate precipitation and Sephadex G-75 gel
chromatography. Molecular weight of purified enzyme was determined as 106 kDa by
SDS-PAGE. Purified protease was stable at 50-60 degrees C and at pH 9.0 for 1 h.
The enzyme activity was increased in the presence of Ca2+, Cu2+, Tween 80 and
Triton X-100, however the enzyme activity was inhibited in the presence of Hg2+,
ethylene diamine tetra acetic acid (EDTA) and H2O2. Proteolytic activity was
completely inhibited by phenyl methyl sulfonyl fluoride (PMSF). The enzyme seems
to be a serine alkaline protease. In the presence of detergents, the protease was
clearly stable and residual activity was between 73-82%.
PMID- 26429302
TI - Targeting microbiota-mitochondria inter-talk: Microbiota control mitochondria
metabolism.
AB - Our aim is to highlight the subtle relationship that exists between microbiota
and mitochondria. Microbiota targets mitochondria by modulating the Reactive
Oxygen Species (ROS) production and the mitochondrial activity through
interactions with toxins, proteins or other metabolites released by gut
microbiota. The intriguing relationship that exists between mitochondria and
microbiota is strengthened by the probable prokaryotic origin of mitochondria.
Emerging data implicates a role for ROS, nitric oxide, Short Chain Fatty Acids
and hydrogen sulfide in the cross-talk between microbiota - mitochondria and
REDOX signaling. Several studies have shown that microbiota act and modulate
mitochondrial activity, and use it as a relay to strengthen host-microbiotal
interaction. This modulation depends on the gut bacterial strain quality and
diversity to increase its pathogenic versus beneficial effects. Furthermore,
based on conclusions from new studies, it is possible that microbiota can
directly interact with the host cell gene expression by favoring bacterial and
mitochondrial DNA insertion in the nuclear genome. The emerging knowledge of
mitochondria-microbiota interaction may be of great importance to better
understand the mechanism of mitochondrial and metabolic diseases, and the
syndromes associated with change in quality and quantity of microbiotal species.
We suggest that microbiota via mitochondrial modulation influence cell
homeostasis and metabolism. The challenge will be to find strategies to modulate
the quality and diversity of microbiota rather than acting on microbiota
metabolites and microbiota related factors. The medicine of tomorrow will be
completely personalized. Firstly there will be a test to show the quality,
quantity and diversity of microbiota, and secondly a preventive or therapeutic
strategy will be administrated (probiotics, diet, prodrug or fecal
transplantation). The era of digital medicine is here.
PMID- 26429303
TI - Biomarkers predicting chemotherapy response in head and neck squamous cell
carcinoma: a review.
AB - BACKGROUND: Biomarkers are increasingly being used in many cancers to select
patients for oncological treatment paradigms based on their inherent genetic
properties. However, in head and neck cancers, there are no personalised
therapies available outside the context of a clinical trial. A number of studies
suggest there are intrinsic tumour properties of head and neck cancers that
affect their response to chemotherapeutic agents. This paper aimed to review
their evidence base. METHOD: A narrative review was conducted following a search
of the PubMed database. RESULTS AND CONCLUSION: The review identified a number of
biomarkers predicting response to chemotherapy in head and neck cancers. The
paper discusses these in detail, and explores where future research could be
directed in order to deliver personalised therapies for patients with head and
neck cancers.
PMID- 26429304
TI - Association of FCGR2A p.R131H and CCL2 c.-2518 A>G gene variants with
thrombocytopenia in patients with dengue virus infection.
AB - FCGR2A and CCL2 gene variants are important in dengue pathogenesis and were
investigated in 122 dengue patients (DENs) [89 dengue fever (DF) and 33 dengue
hemorrhagic fever (DHF)] and 107 healthy controls (HCs) to find out their
association with severity of dengue. Genotype frequencies of FCGR2A p.R131H and
CCL2 c.-2518 A > G polymorphisms were not different between DF, DHF and HC.
Significantly higher frequency of R/R genotype of FCGR2A p.R131H was observed in
DEN cases with thrombocytopenia (TP) while the G/G genotype of CCL2 c.-2518 A > G
was observed only in DEN cases with TP (p < 0.005). These results suggest that
FCGR2A and CCL2 gene variants were associated with the risk of TP in dengue
infections.
PMID- 26429307
TI - Improved flow cytometry based cytotoxicity and binding assay for clinical
antibody HLA crossmatching.
AB - The presence of preformed donor-specific HLA antibodies leads to early antibody
mediated kidney allograft rejection. Therefore, detection and avoidance of donor
reactive HLA antibodies prior to transplantation is of outmost importance in
order to minimize the risk of rejection. Detection of pre-formed HLA antibodies
is currently performed using complement-dependent cytotoxicity (CDC) assay alone
or together with a flow cytometry based crossmatch (FCXM). This study was
initiated to further evaluate our recently developed flow cytometry based
procedure for determination of both cytotoxicity of and IgG binding to donor
derived lymphocytes by HLA antibodies. Highly enriched immuno-magnetic bead
purified T and B lymphocytes were used as target cells for patient sera using 96
well plates. Importantly, the assay shows high sensitivity and specificity as
determined by HLA typed donor cells and serum with defined HLA antibody IgG and
C1q. Based on this and additional data generated in this paper, such as
evaluation of appropriate serum and complements incubation times and assay
reproducibility and stability, will enable us to more rapidly implement this
assay in our clinical laboratory routines. In addition, we demonstrate that FCtox
crossmatching of deceased donor cells has superior specificity compared to
conventional CDC assay especially regarding high frequencies of false-positive
reactions.
PMID- 26429308
TI - WITHDRAWN: Association between interleukin 8 -251 A/T and +781 C/T polymorphisms
and coronary artery disease risk.
PMID- 26429305
TI - Characterization of CD4/CD8+ alphabeta and Vgamma2Vdelta2+ T cells in HIV
negative individuals with different Mycobacterium tuberculosis infection
statuses.
AB - BACKGROUND: The immune responses of T cell subsets among patients with different
Mycobacterium tuberculosis (M.tb) infection statuses [i.e., active tuberculosis
(ATB), latent tuberculosis infection (LTBI) and non-infection (healthy control,
HC)] have not been fully elucidated in HIV-negative individuals. Specifically,
data are limiting in high tuberculosis epidemic regions in China. To investigate
the distributions and functions of T cell subsets (i.e., CD3+, CD4+, CD8+
alphabeta and Vgamma2Vdelta2+ T cells) in HIV-negative subjects with different
M.tb infection statuses, we conducted a case-control study that enrolled 125
participants, including ATB patients (n = 46), LTBI subjects (n = 34), and HC (n
= 45). RESULTS: An IFN-gamma release assay (IGRA) was employed to screen LTBI
subjects. Whole blood cell surface staining and flow cytometry were used to
detect phenotypic distributions of T cells in the peripheral blood mononuclear
cells (PBMCs) and tuberculous pleural fluid mononuclear cells (PFMCs). PPD and
the phosphorylated antigen HMBPP were employed as stimulators for the detection
of M.tb antigen-specific T cell functions via intracellular cytokine staining
(ICS). The absolute numbers of T cell subsets, including CD3+ CD4+, CD3+ CD8+
alphabeta and Vgamma2Vdelta2+ T cells, were significantly reduced in active
tuberculosis compared with latent tuberculosis or the healthy controls.
Importantly, PPD-specific CD3+ CD4+ and CD3+ CD8+ alphabeta T cells and HMBPP
specific Vgamma2Vdelta2+ T cells in ATB patients were also significantly reduced
compared to the LTBI/HC subjects (P<0.05). In contrast, the proportion of CD4+ T
cells in PFMCs was higher compared to PBMCs, while CD8+ and Vgamma2Vdelta2+ T
cells in PFMCs were lower compared to PBMCs (all P < 0.05). PPD-specific CD4+ T
cells predominated among CD3+ T cells in PFMCs. CONCLUSIONS: Cellular immune
responses are impaired in ATB patients. Antigen-specific CD4+ T cell may migrate
from the periphery to the lesion site, where they exert anti-tuberculosis
functions.
PMID- 26429306
TI - Contribution of dendritic cell immunoreceptor (DCIR) polymorphisms in
susceptibility of systemic lupus erythematosus and primary Sjogren's syndrome.
AB - Dendritic cell immunoreceptor (DCIR) has previously shown an association with
rheumatoid arthritis (RA) in Caucasians and Han Chinese. This study was aimed to
further investigate whether DCIR polymorphisms are novel susceptibility factors
for other autoimmune diseases, i.e. systemic lupus erythematosus (SLE) and
primary Sjogren's syndrome (SS). A total of 1502 patients with SLE, 476 patients
with primary SS, and 1278 non-related healthy controls were enrolled in the
study. The single-nucleotide polymorphisms (SNPs) rs2377422 and rs10840759 were
genotyped using TaqMan assay. The differences in allelic and genotypic
distribution between two groups were assessed using Pearson chi-square test, and
logistic regression adjusting for age and sex, respectively. P-value < 0.025 was
considered statistically significant by Bonferroni correction. The SNP rs2377422
confers an increased susceptibility risk to both SLE (allele model: P = 7.65 *
10(-4), OR 1.20; genotype recessive model: P = 0.012, OR 1.29), and primary SS
(allele model: P = 3.74 * 10(-4), OR 1.31; genotype dominant model: P = 1.62 *
10(-4), OR 2.02). There is no association between rs10840759 and SLE or primary
SS. In conclusion, DCIR SNP rs2377422 is a novel genetic susceptibility factor
for both SLE and primary SS.
PMID- 26429309
TI - Genetic variation in Micro-RNA genes of host genome affects clinical
manifestation of symptomatic Human Cytomegalovirus infection.
AB - BACKGROUND: Micro-RNAs are implicated in various physiological and pathologic
processes. In this study, we tested whether Micro-RNA gene variants of host
genome affect clinical manifestation of symptomatic HCMV infection. METHODOLOGY:
HCMV infection was detected by fluorescent PCR and immuno-histochemistry. The
detection of genetic variants of four studied Micro-RNA tag-SNPs was done through
PCR-RFLP assay and validated with DNA sequencing. RESULTS: We observed an
increased risk ranged from 3-folds to 5-folds among symptomatic HCMV cases for
mutant genotype of rs2910164 (crude OR=3.11, p=0.009 and adjusted OR=3.25,
p=0.007), rs11614913 (crude OR=3.20, p=0.006 and adjusted OR=3.48, p=0.004) and
rs3746444 (crude OR=4.91, p=0.002 and adjusted OR=5.28, p=0.002) tag-SNPs.
Interestingly, all the tag-SNPs that were significant after multiple comparisons
at a FDR of 5% in symptomatic HCMV cases remained significant even after
bootstrap analysis, providing internal validation to these results. Multifactor
Dimensionality Reduction (MDR) analysis revealed 5-folds increased risk for
symptomatic HCMV cases under the four-factor model (rs2910164, rs2292832,
rs11614913 and rs3746444). CONCLUSIONS: These results suggest that Micro-RNA gene
variants of host-genome may affect clinical manifestation of symptomatic HCMV
infection.
PMID- 26429310
TI - Single nucleotide polymorphisms in immune system genes and their association with
clinical symptoms persistence in dengue-infected persons.
AB - This study was undertaken to determine the prevalence of dengue clinical symptom
persistence during 60days of disease follow up, in patients of Espirito Santo
state (ES)-Brazil and to evaluate the relation of single nucleotide polymorphisms
(SNPs) in FcgammaRIIa, CD209, VDR, TNF-alpha, IL-4, IL-6 and IFN-gamma genes with
symptom persistence. During 2012-2013, 96 blood samples from individuals
diagnosed with symptomatic dengue were collected. Clinical symptom persistence in
60days of follow-up was assessed by a clinical and epidemiological questionnaire
filled in 4 interviews. SNP genotyping was performed by polymerase chain reaction
restriction fragment length polymorphism (PCR-RFLP). In two months of monitoring
the dengue infection, we observed that symptoms persisted in 38.5% (37/96) of
dengue patients at the end of the first month (D30) and in 11.5% (11/96) of
dengue patients at the end of the second month (D60). Our results show an
association between FcgammaRIIa, TNF-alpha and IL-6 gene SNPs and symptom
persistence and an association trend with CD209, IL-4 and IFN-gamma gene SNPs.
Our findings may increase the knowledge on the pathophysiological mechanisms of
persistent symptoms of infection with the dengue virus (DENV) and thus help the
clinical management of patients.
PMID- 26429311
TI - SOCS3 and its role in associated diseases.
AB - Cell-cell communication depends on cytokine and growth factor network. Bound to
their receptors on the surface of target cell, these glycoproteins initiate a
range of intracellular events. Subsequent dissipation of receptor signaling is
essential to ensure the response of the cell does not become pathogenic. The
Suppressors of cytokine signaling (SOCS) proteins are a family of proteins
induced to attenuate cytokine signal transduction in response to signals from a
diverse range of cytokines and growth factors. Current evidence indicates that
intracellular JAK-STAT (Janus kinase-signal transducer and activator of
transcription) signaling not only governs cytokine-induced immunological
responses but also rapidly initiates SOCS expression and its biological
functions. This review focuses on current understanding of SOCS3, a member of
SOCS family. SOCS3 binds to JAK, certain cytokine receptors in intracellular
domain, and some signaling molecules, which results in suppressing further
signaling events in the cell. Studies using conditional knockout mice have shown
that SOCS3 protein is the key physiological regulator and plays an important
pathological role in immune homeostasis. Dysregulation of SOCS3 functions can
cause a variety of diseases, including allergy, autoimmune diseases, inflammation
and cancer.
PMID- 26429312
TI - Association of a coding polymorphism in Fc gamma receptor 2A and graft survival
in re-transplant candidates.
AB - The family of Fc gamma receptors (FcgammaRs) is involved in mediating
immunological effector functions. FcgammaRs are differentially expressed on
immune cells and can act either activating or inhibitory, with FcgammaR2A
belonging to the first group. The polymorphism H131R (rs1801274) in FCGR2A has
been associated with acute rejection and can shift the overall balance between
activating and inhibitory FcgammaRs. Anti-HLA allo-antibodies in transplant
recipients have been identified as risk factor for organ survival after
transplantation. In this study we genotyped FCGR2A H131R in 200 patients who had
undergone kidney transplantation and experienced loss of graft function. FCGR2A
polymorphism was related to graft survival and anti-HLA antibodies. Graft
survival was calculated as the time interval between transplantation and return
to chronic dialysis after transplantation. The gene frequency of FCGR2A R/R131
was found significantly more often in patients with earlier (?60months) compared
to patients with later (>60months) graft failure. Overall patients homozygous for
R/R131 had a significantly shorter graft survival, compared to H/H131 or H/R131
which is even more pronounced, when anti-HLA antibodies were present. These data
suggest, that FCGR2A polymorphisms constitute a risk factor for graft loss
following kidney transplantation and that this effect is related to anti-HLA
antibodies.
PMID- 26429313
TI - Impact of population admixture on the distribution of immune response co
stimulatory genes polymorphisms in a Brazilian population.
AB - Co-stimulatory molecules are essential in the orchestration of immune response
and polymorphisms in their genes are associated with various diseases. However,
in the case of variable allele frequencies among continental populations, this
variation can lead to biases in genetic studies conducted in admixed populations
such as those from Brazil. The aim of this study was to evaluate the influence of
genomic ancestry on distributions of co-stimulatory genes polymorphisms in an
admixed Brazilian population. A total of 273 individuals from the north of Brazil
participated in this study. Nine single nucleotide polymorphisms in 7 genes
(CD28, CTLA4, ICOS, CD86, CD40, CD40L and BLYS) were determined by polymerase
chain reaction-restriction fragment length polymorphism. We also investigated 48
insertion/deletion ancestry markers to characterize individual African, European
and Amerindian ancestry proportions in the samples. The analysis showed that the
main contribution was European (43.9%) but also a significant contribution of
African (31.6%) and Amerindian (24.5%) ancestry. ICOS, CD40L and CD86
polymorphisms were associated with genomic ancestry. However there were no
significant differences in the proportions of ancestry for the other SNPs and
haplotypes studied. Our findings reinforce the need to apply AIMs in genetic
association studies involving these polymorphisms in the Brazilian population.
PMID- 26429314
TI - Repressing PU.1 by miR-29a* in NK cells of HCV patients, diminishes its cytolytic
effect on HCV infected cell models.
AB - OBJECTIVES: Natural killer cells are immune safeguards against HCV infection.
PU.1 is a pivotal transcription factor in the development of NK cells. This study
aimed at studying the regulatory effect of miRNAs on both development and
function of NK cells isolated from HCV patients. METHODS: NK cells were isolated
from 17 chronic HCV patients and 12 healthy controls; after which miRNA and mRNA
were quantified using qRT-PCR. Manipulating miRNA expression using mimics and
antagomirs, was performed followed by investigating downstream targets as well as
viral abundance. RESULTS: PU.1 expression levels were upregulated in NK cells of
HCV patients. In silico analysis revealed PU.1 to be a potential downstream
target of miR-29a(*), where miR-29a(*) overexpression in NK cells caused a
significant downregulation in PU.1 mRNA. Forcing miR-29a(*) caused a
downregulation of the cytotoxicity determinant NK activating receptor (NKG2D) via
upregulation of miR-155. Moreover, perforin-1 mRNA was found to be downregulated
upon forcing the expression of miR-29a(*) in NK cells of HCV patients. This
decrease in NK cytolytic function was accompanied by an 80% viral load increase
in cocultured HCVcc cell models. CONCLUSIONS: This study showed that HCV
infection might abrogate NK cytotoxic potential through altering PU.1, NKG2D
receptor and perforin molecules.
PMID- 26429315
TI - Association of PTPN22 gene polymorphisms with chronic hepatitis B virus infection
in Chinese Han population.
AB - Lymphoid protein tyrosine phosphatase encoded by protein tyrosine phosphatase non
receptor 22 (PTPN22) gene plays an important regulatory role in T- and B-cell
activation. This study investigated PTPN22 -1123G/C and intron 16 T/C
polymorphisms in 372 patients with chronic hepatitis B virus (HBV) infection, 72
HBV infection resolvers and 273 healthy controls. Genotypic association tests
between groups assuming codominant, dominant or log-additive genetic models were
performed. In recessive model, PTPN22 -1123G/C genotype GG in healthy controls
was more frequent than infection resolvers (P=0.037, OR=3.606, 95%CI=1.079
12.053) and this genotype in HBV patients was more frequent than resolvers
although the difference was not significant (P=0.059). The PTPN22 intron 16 T/C
genotype TC in cirrhosis patients was significantly higher than asymptomatic
carriers (ASC) in codominant (P=0.028, OR=9.792, 95%CI=1.281-74.832) and
overdominant (P=0.025, OR=10.142, 95%CI=1.332-77.214) models. This genotype in
hepatocellular carcinoma (HCC) patients was significantly higher than ASC in
codominant (P=0.034, OR=9.200, 95%CI=1.176-71.990) and overdominant (P=0.030,
OR=9.677, 95%CI=1.241-75.442) models. These findings suggest that PTPN22
polymorphisms may predispose the chronicity or the development of cirrhosis and
HCC in HBV infection.
PMID- 26429316
TI - The prevalence of Selective Immunoglobulin M Deficiency (SIgMD) in Iranian
volunteer blood donors.
AB - BACKGROUND: Selective Immunoglobulin M Deficiency (SIgMD) is known as a rare
primary immunodeficiency characterized by an isolated deficiency of serum IgM.
Other immunoglobulin levels and T-cell immunity are usually normal; although IgE
may be elevated. SIgMD can be asymptomatic or with various bacterial and viral
infections. It can also be associated with autoimmune diseases or malignancies.
In the present study, we report for the first time, the prevalence of SIgMD in
Iranian healthy adult population. MATERIALS AND METHODS: A total of 3436 healthy
donors were examined in the study; from August, 2006 to April, 2008. Serum IgM
concentration was measured using the nephelometric method. We considered serum
IgM less than 30 mg/dl as IgM deficiency. RESULTS: Among 3436 participants, 65%
were male and 34% were female; aging from 17 to 72 years (38.18+/-10.78).
Thirteen individuals were detected as IgM deficient subjects with the male to
female ratio of 11/2, the prevalence of 0.37% and the frequency of 1/265. The
mean serum IgM level was 24+/-4.56 (16-29 mg/dl) in these cases. Among 13 IgM
deficient subjects, 7 cases were available for evaluating the clinical
manifestations. In addition to atopic dermatitis which was the most common
symptom in these patients, others were allergic rhinitis, food allergy, urinary
tract infection and skin fungal infection. Two patients had no history of
infectious disease or atopic conditions. CONCLUSION: In the present study we
could determine the prevalence of SIgMD in our adult population (0.37%). The most
common comorbid condition was atopy. Neither severe or life-threatening
infections, nor autoimmune diseases (based on their history; the antibody
screening was not performed as part of this study) or malignancies were found in
these patients. Further evaluation is recommended to elucidate the prevalence of
SIgMD among patients with recurrent infections.
PMID- 26429317
TI - Functional relevance for type 1 diabetes mellitus-associated genetic variants by
using integrative analyses.
AB - AIM: Type 1 diabetes mellitus (type 1 DM) is an autoimmune disease. Although
genome-wide association studies (GWAS) and meta-analyses have successfully
identified numerous type 1 DM-associated susceptibility loci, the underlying
mechanisms for these susceptibility loci are currently largely unclear. METHODS:
Based on publicly available datasets, we performed integrative analyses (i.e.,
integrated gene relationships among implicated loci, differential gene expression
analysis, functional prediction and functional annotation clustering analysis)
and combined with expression quantitative trait loci (eQTL) results to further
explore function mechanisms underlying the associations between genetic variants
and type 1 DM. RESULTS: Among a total of 183 type 1 DM-associated SNPs, eQTL
analysis showed that 17 SNPs with cis-regulated eQTL effects on 9 genes. All the
9 eQTL genes enrich in immune-related pathways or Gene Ontology (GO) terms.
Functional prediction analysis identified 5 SNPs located in transcription factor
(TF) binding sites. Of the 9 eQTL genes, 6 (TAP2, HLA-DOB, HLA-DQB1, HLA-DQA1,
HLA-DRB5 and CTSH) were differentially expressed in type 1 DM-associated related
cells. Especially, rs3825932 in CTSH has integrative functional evidence
supporting the association with type 1 DM. CONCLUSIONS: These findings indicated
that integrative analyses can yield important functional information to link
genetic variants and type 1 DM.
PMID- 26429318
TI - Frequent IgG subclass and mannose binding lectin deficiency in patients with
chronic fatigue syndrome.
AB - Chronic fatigue syndrome (CFS) is a severe disease characterized by various
symptoms of immune dysfunction. CFS onset is typically with an infection and many
patients suffer from frequently recurrent viral or bacterial infections.
Immunoglobulin and mannose binding lectin (MBL) deficiency are frequent causes
for increased susceptibility to infections. In this study we retrospectively
analysed 300 patients with CFS for immunoglobulin and MBL levels, and B-cell
subset frequencies. 25% of the CFS patients had decreased serum levels of at
least one antibody class or subclass with IgG3 and IgG4 subclass deficiencies as
most common phenotypes. However, we found elevated immunoglobulin levels with an
excess of IgM and IgG2 in particular in another 25% of patients. No major
alteration in numbers of B cells and B-cell subsets was seen. Deficiency of MBL
was found in 15% of the CFS patients in contrast to 6% in a historical control
group. In a 2nd cohort of 168 patients similar frequencies of IgG subclass and
MBL deficiency were found. Thus, humoral immune defects are frequent in CFS
patients and are associated with infections of the respiratory tract.
PMID- 26429319
TI - Influence of dopamine receptor gene polymorphisms on circulating T lymphocytes: A
pilot study in healthy subjects.
AB - Dopamine is a key transmitter in the neuroimmune network, acting through five
dopaminergic receptors (DR): the D1-like D1 and D5 and the D2-like D2, D3 and D4.
Several DR gene variants exist and may affect DR expression and activity. We
assessed total lymphocytes, CD3+, CD4+ and CD8+ T lymphocytes in peripheral blood
of healthy subjects and their association with selected DR gene variants (DRD1
rs4532 and rs686, DRD5 rs6283, DRD2 rs1800497 and rs6277, DRD3 rs6280 and
rs1800828, DRD4 rs747302 and 7 48-base pair VNTR). DRD1 rs4532 and rs686 and DRD5
rs6283 were associated with total lymphocytes, and with CD3+ and CD4+ (but not
CD8+) T lymphocytes, while none of the D2-like DR gene variants showed any
association with lymphocyte counts. An arbitrary score based on the activity of
D1-like vs D2-like DR correlated with total lymphocytes, CD3+ and CD4+ T cells
(but not with CD8+ T cells). The association between D1-like DR gene variants and
lymphocyte count, and in particular with CD4+ (but not CD8+) T lymphocytes, may
imply a functional prevalence of D1-like over D2-like DR in CD4+ T cells. This is
the first study showing an influence of DR gene polymorphisms on lymphocyte
count, and in particular on CD4+ T cells. Future studies should address the
possible association between DR gene variants and the immune function in health
and disease. The relevance of these findings for the immune effects of
dopaminergic agents should be also carefully examined.
PMID- 26429320
TI - Association analysis of class II cytokine and receptor genes in vitiligo
patients.
AB - The loss of melanocytes in vitiligo is mainly attributed to defective autoimmune
mechanisms and lately autoinflammatory mediators have become more emphasized.
Among these, a number of class II cytokines and their receptors have displayed
altered expression patterns in vitiligo. Thus, we selected 30 SNPs from the
regions of respective genes to be genotyped in Estonian case-control sample (109
and 328 individuals, respectively). For more precise analyses, patients were
divided into subgroups based on vitiligo progression activity, age of onset, sex,
occurrence of vitiligo among relatives, extent of depigmented areas, appearance
of Kobner's phenomenon, existence of halo nevi, occurrence of spontaneous
repigmentation, and amount of thyroid peroxidase antibodies. No associations
appeared in whole vitiligo group. In subgroups, several allelic and haplotype
associations were found. The strongest involved SNPs rs12301088 (near IL26 gene),
that was associated with familial vitiligo and existence of halo nevi, and
rs2257167 (IFNAR1 gene), that was associated with female vitiligo. Additionally,
haplotypes consisting of rs12301088 and rs12321603 alleles (IL26-IL22 genes),
that were associated with familial vitiligo and existence of halo nevi. In
conclusion, several genetic associations with vitiligo subphenotypes were
revealed and functional explanations to these remain to be determined in
respective studies.
PMID- 26429321
TI - Counteractive functions are encrypted in the residues of CD154.
AB - CD40, as a single receptor that binds CD154 (CD40-ligand or CD40L), regulates
counteractive effector functions such as production of pro- and anti-inflammatory
cytokines. Therefore, we examined whether such dual messages are encrypted in
CD40L. As such message encryption was never investigated, we hypothesized that
mutation of certain amino acid residues should in principle enhance pro
inflammatory cytokine production whereas mutation of some others would enhance
anti-inflammatory cytokine secretion. We mutated six such residues, which were
previously showed to participate in CD40L function. Here, we report that the
mutant CD154 129E->V was superior to the wild-type CD154 in killing of Leishmania
donovani, induction of inducible nitric oxide synthase (iNOS) and production of
IL-12 and relative phosphorylation of p38MAPK and ERK-1/2 in PBMC-derived
macrophages. By contrast, 128S->V promoted L. donovani survival, reducing iNOS,
but increasing IL-10 expression and predominant ERK-1/2 phosphorylation. The
mutant 144G->V did not have significant effects. Other mutants (142E->V, 143K->A,
145Y->F) mimicked the wild-type CD154. Molecular dynamics simulation suggested
that these mutations induced differential conformational changes in the CD40
CD154 complex. Therefore, assortment of the contrasting messages encrypted in a
given ligand performing counteractive functions presents a novel fundamental
biological principle that can be used for devising various therapies.
PMID- 26429322
TI - Study of genetic diversity of KIR and TLR in the Rabhas, an endogamous primitive
tribe of India.
AB - The Rabha tribe is a little known small endogamous population belonging to Indo
mongoloid group of north-eastern India. We have analyzed 16 KIR and 5 TLR gene
polymorphisms in the Rabha population of northern West Bengal, India for the
first time. The observed frequencies of the KIR genes (except framework and
pseudogene loci) ranged between 0.26 (KIR2DS3) and 0.96 (KIR2DL1). Comparisons
based on KIR polymorphism have revealed that although the Rabhas are of Indian
origin the presence of mongoloid component in their gene pool cannot be denied.
The frequencies of the 5 TLR genes ranged between 0.90 (TLR4) and 0.46 (TLR5).
TLR variations found in the Rabhas may play a synergistic role in fighting
against the bacterial invasions. Our results may contribute to the understanding
of (1) genetic background and extent of genetic admixture in the Rabhas, (2)
population migration events and (3) KIR-disease-TLR interactions.
PMID- 26429323
TI - Therapeutic potential of IL-15 in rheumatoid arthritis.
AB - Rheumatoid arthritis (RA) is a chronic, destructive inflammatory autoimmune
disease. Cytokine-mediated immunity has been found to play an important role in
the pathogenesis of autoimmune diseases including RA. Recently, much attention
has been paid on the role of IL-15, which is a member of the 4 alpha-helix bundle
cytokine family. IL-15 was detected in serum and synovial fluid from RA patients
and arthritis mice models. Moreover, administration of IL-15 leads to the
development of severe inflammatory arthritis, suggesting that IL-15 may be
therapeutically relevant in RA. Therefore, targeting IL-15 may be significantly
important and valuable. In this article, we discuss the biological features and
effects of IL-15 and summarize recent advances on the pathological roles of IL-15
in RA and treatment for RA.
PMID- 26429324
TI - Receptor for advanced glycation end products (RAGE) gene polymorphism and
cardiovascular disease in end-stage renal disease patients.
AB - BACKGROUND/OBJECTIVES: Receptor for advanced glycation end products (RAGE)
contributes to the pathogenesis of vascular and inflammatory diseases. We
investigated whether the functional polymorphism in the promoter region of the
RAGE gene (-374 T/A) influences development of cardiovascular disease in the end
stage renal disease (ESRD) patients. METHODS: The cohorts of 1866 ESRD patients
and 1143 healthy subjects were genotyped by polymerase chain reaction (PCR) for
the RAGE variant rs1800624. RESULTS: The genotype and allele frequencies did not
differ significantly between ESRD patients and controls. There was no significant
difference in the genotype distribution when patients with CVD were compared to
those without it (p for A allele = 0.62). After stratifying CVD patients
according to CVD clinical phenotype, the ESRD patients with stroke had a lower
frequency of A allele than patients without CVD (0.12 vs. 0.21, p = 0.027). To
confirm this finding, we genotyped 163 patients with ischemic stroke but without
renal disease. In this group, the AA/TA genotypes were also significantly
associated with lower risk of stroke (OR 0.46, p = 0.0002). CONCLUSION: Our data
suggest that the presence of the A allele of -374 T/A polymorphism in the RAGE
gene has a protective effect against stroke.
PMID- 26429325
TI - Poor functional immune recovery in aged HIV-1-infected patients following
successfully treatment with antiretroviral therapy.
AB - Aging is now a well-recognized characteristic of the HIV-infected population and
both AIDS and aging are characterized by a deficiency of the T-cell compartment.
The objective of the present study was to evaluate the impact of antiretroviral
(ARV) therapy in recovering functional response of T cells to both HIV-1-specific
ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who
responded to ARV therapy by controlling virus replication and elevating CD4(+) T
cell counts. Here, we observed that proliferative response of T-cells to either
HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in
older antiretroviral (ARV)-treated patients. With regard to cytokine profile,
lower levels of IFN-gamma, IL-17 and IL-21, associated with elevated IL-10
release, were produced by Env- or TT-stimulated T-cells from older patients. The
IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-gamma and IL-21
release in older patients. Finally, even after a booster dose of TT, reduced anti
TT IgG titers were quantified in older AIDS patients and it was related to both
lower IL-21 and IFN-gamma production and reduced frequency of central memory T
cells. Our results reveal that ARV therapy, despite the adequate recovery of
CD4(+) T cell counts and suppression of viremia, was less efficient in recovering
adequate immune response in older AIDS patients.
PMID- 26429326
TI - FAS -670 A/G polymorphism may be associated with the depletion of CD4(+) T
lymphocytes in HIV-1 infection.
AB - In this study, the polymorphisms in the FAS and FASL genes was investigated in a
sample of 198 HIV-1-seropositive individuals and 191 seronegative controls to
evaluate a possible association between polymorphisms and the infection. The
identification of the A and G alleles of the FAS -670 polymorphism was
accomplished through polymerase chain reaction assays followed by digestion with
the restriction enzyme MvaI. The identification of the A and G alleles of the FAS
-124 polymorphism and the T and delT alleles of the FAS -169 polymorphism were
performed using the amplification-created restriction site method followed by
restriction fragment length polymorphism reactions. The comparative analysis of
allelic and genotypic frequencies between the groups did not reveal any
significant differences. However, the quantitative analysis of CD4(+) T
lymphocytes suggests that the G allele of the FAS -670 A/G polymorphism can be a
protective factor against the depletion of these cells in the course of an HIV-1
infection. Polymorphisms in the FAS and FASL genes were not associated with the
number of CD8(+) T lymphocytes or the plasma viral load. Our findings suggest
that the FAS -670 polymorphism may be associated with apoptosis of CD4(+) T
lymphocytes after infection by HIV-1.
PMID- 26429327
TI - Role of stem cells in spondyloarthritis: Pathogenesis, treatment and
complications.
AB - Spondyloarthritis (SpA) is a family of interrelated inflammatory arthritis that
includes ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis,
arthritis related to inflammatory bowel disease and undifferentiated SpA. The
classification, epidemiology, pathogenesis and treatment of SpA have been
extensively reviewed in the published literature. Reviews on the use of stem
cells in various autoimmune diseases in general are also common. However, a
review on the role of stem cells in SpA is currently lacking. This review focuses
on the involvement of stem cells in the pathogenesis of SpA and the application
of different types of stem cells in the treatment of SpA. It also addresses some
of the complications which may arise as a result of the use of stem cells in the
treatment of SpA.
PMID- 26429328
TI - Comparative analysis of how immune sensitization is defined prior to lung
transplantation.
AB - BACKGROUND: Immune sensitization prior to lung transplantation may be associated
with worse survival. Using solid phase assays to define sensitization, we
assessed the relationship between PRA status, donor specific anti-HLA antibodies
(DSA) pre-transplant, cytotoxic cross match results and the clinical outcomes
following lung transplantation. METHODS: Luminex assays determined the presence
of antibodies to class I and class II MHC molecules prior to lung
transplantation. At the time of transplant, the PRA status, the presence of DSA
and prospective cytotoxic cross match result were analysed in 195 patients
undergoing lung transplantation between June 2008 and June 2012. Clinical
outcomes analysed included acute cellular and antibody-mediated rejection,
chronic lung allograft dysfunction (CLAD) and mortality. RESULTS: At the time of
transplant, 45% of patients had a positive PRA and 29% had DSA. On univariate
analysis, the presence of pre-transplant class I or II anti-HLA donor-specific
antibodies was not associated with the development of chronic lung allograft
dysfunction (CLAD) despite significant associations with PRA status and B-cell
crossmatch. CONCLUSION: Defining sensitization using solid phase assays provide
additional details regarding donor-specific sensitization but did not provide
additional prognostic information to that provided by historically available cell
based cross-match assays.
PMID- 26429329
TI - A review of 42 cases of intestinal pseudo-obstruction in patients with systemic
lupus erythematosus based on case reports.
AB - Intestinal pseudo-obstruction (IpsO) is considered a severe manifestation of
systemic lupus erythematosus (SLE) characterized by clinical and radiological
evidence of intestinal obstruction with no identifiable mechanical lesion. We
performed a systematic review to document IpsO in SLE. Twenty-eight articles with
42 patients were included. The median age of onset of IpsO was 27.5 (10-57)
years. The female to male ratio was 38:4. Twenty-two (52.4%) patients had IpsO as
the initial presentation of their underlying lupus. Three (7.1%) patients
manifested in inactive lupus. The duration of abdominal symptoms before admitted
ranged from 3 days to 3 years, however most of the patients responded well to
systemic corticosteroid or immunosuppressive treatment within 2 days to about 3
months. Concomitant ureterohydronephrosis was present in approximately three
fourths of the cases. More interestingly, 4 patients presented hepatobiliary
dilatation without mechanical obstruction together with IPO and
ureterohydronephrosis. In conclusion, IpsO is an uncommon but important
manifestation of SLE. The finding of coexisting ureterohydronephrosis and
hepatobiliary dilatation suggests that there may be generalized visceral muscle
dysmotility. Early recognition of IpsO is necessary to institute appropriate
medical treatment and to avoid inappropriate surgical intervention.
PMID- 26429330
TI - Role of galectin-3 in the pathogenesis of bladder transitional cell carcinoma.
AB - Galectins constitute an evolutionary conserved family that binds to beta
galactosides. There is growing evidence that galectins are implicated in
essential biological processes such as cellular communication, inflammation,
differentiation and apoptosis. Galectin-3 is one of the best-known galectins,
which is found in vertebrates. Galectin-3 has been shown to be expressed in some
cell lines and plays important roles in several physiological and pathological
processes, including cell adhesion, cell activation and chemoattraction, cell
cycle, apoptosis, cell growth, and differentiation. Moreover, this galectin is of
interest due to its involvement in regulation of cancer. Changes in galectin-3
expression are commonly seen in cancerous and pre-cancerous conditions and
galectin-3 may be involved in the regulation of cancer cell activities that
contribute to tumourigenesis, cancer progression and metastasis. Finally,
galectin-3 seems to be involved in cell events in tumor microenvironment, and
therefore it could be considered as a target in transitional cell carcinoma
therapies. This review aims to describe recent progress in understanding the role
of galectin-3 in cancer biology, with emphasis on bladder tumor progression and
metastasis.
PMID- 26429331
TI - Association of monocyte chemoattractant protein 1 (MCP-1) gene polymorphism with
lupus nephritis in Egyptian patients.
AB - BACKGROUND AND STUDY AIM: Monocyte chemoattractant protein-1 (MCP-1) is a member
of CC chemokine that plays an important role in the recruitment of
monocytes/macrophages into renal tubulointerstitium. A biallelic A/G polymorphism
at position ~2518 in the MCP-1 gene was found to regulate MCP-1 expression. MCP-1
and its A/G gene polymorphism have been implicated in the pathogenesis of some
renal diseases. The aim of the study was to investigate the role of the MCP-1
gene polymorphism as early predictors of the development of glomerulonephropathy
in SLE patients. We also aimed to measure the serum and urinary levels of MCP-1
in patients with SLE, to find out its relation to clinical disease activity.
METHODS: 140 SLE patients (100 with nephritis and 40 without nephritis) and 80
controls were included in this study. MCP-1 gene polymorphism was analyzed by
polymerase chain reaction. Serum and urine MCP-1 level were measured using high
sensitivity enzyme-linked immunosorbent assay. RESULTS: The A/A genotype was more
common in controls than in SLE patients, whereas both the A/G (P<0.000) and G/G
(P<0.000) genotypes were more frequent in SLE patients. Carriers of G allele of
the MCP-1 ~2518 polymorphism had more than 7 fold increased risk to develop
glomerulo-nephropathy in patients with SLE. High MCP-1 circulating levels
production from patients with A/G and G/G genotypes was significantly higher than
in A/A genotype. In addition there were significant differences in the mean
levels of serum MCP-1 (P<0.001) and urinary MCP-1 (P<0.001) between patients and
controls. CONCLUSION: The present study provides a new evidence that the presence
of MCP-1 A (-2518) G gene polymorphism and high circulating MCP-1 levels can play
an important role in the development of SLE and nephropathy in Egyptians.
PMID- 26429332
TI - ER stress-inducible protein MANF selectively expresses in human spleen.
AB - Mesencephalic astrocyte-derived neurotrophic factor (MANF; also known as arginine
rich, mutated in early tumors; ARMET), is an ER stress-inducible protein, and
widely expressed in mammalian tissues. In this study, we are interested in the
profile of MANF expression in human splenocytes. Three patients with spleen
trauma were enrolled in this study. Immunohistochemistry and immunofluorescence
were used to detect MANF expression in the four types of cells, including T
cells, B cells, plasma cells, and macrophages in spleens by using the specific
antibodies of anti-CD3, anti-CD20, anti-CD138, and anti-CD68, respectively. We
found that MANF-positive cells extensively distributed in the red pulp and
marginal-zone of spleen, and MANF was almost localized in the cytoplasm of
splenocytes. Double immunofluorescent staining results showed that MANF localized
mainly in the plasma cells and macrophages, but not in T and B cells. Meanwhile,
we found that some MANF-positive cells expressed ER stress-related proteins,
including ATF6, XBP1s, BiP, and CHOP. These results suggest that the selective
expression of MANF in splenocytes may be involved in plasma cell differentiation
and immune regulation.
PMID- 26429333
TI - Psychosocial Aspects of Hearing Loss in Children.
AB - Pediatric hearing loss changed more in the past two decades than it had in the
prior 100 years with children now identified in the first weeks of life and fit
early with amplification. Dramatic improvements in hearing technology allow
children the opportunity to listen, speak and read on par with typically hearing
peers. National laws mandate that public and private schools, workplaces, and
anywhere people go must be accessible to individuals with disabilities. In 2015,
most children with hearing loss attended mainstream schools with typically
hearing peers. Psychosocial skills still present challenges for some children
with hearing loss.
PMID- 26429334
TI - Diagnostic Evaluation of Children with Sensorineural Hearing Loss.
AB - The cause of pediatric sensorineural hearing loss is diverse, comprising genetic,
acquired, and idiopathic conditions. Identifying the specific cause requires that
children undergo thorough otolaryngologic and audiometric evaluations, which
generally include laboratory tests and temporal bone imaging studies. Clinical
genetics and ophthalmologic consultations are also frequently warranted. A
sequential diagnostic approach has been shown to be both prudent and cost
effective. Although a definitive cause is being established, amplification and a
comprehensive treatment strategy should be initiated to ensure that
developmental, auditory, and speech and language delays are minimized.
PMID- 26429335
TI - Parasite clearance after malaria therapy: staying a step ahead of drug
resistance.
AB - The discovery and development of the artemisinin class of antimalarial drugs is
one of the great recent success stories of global health. However, after at least
two decades of successful use, resistance has finally emerged and appears to be
spreading rapidly throughout South-East Asia in spite of our best efforts at
containment. If this were also to occur in Africa, it would have disastrous
implications for the continent subject to the world's greatest burden of
Plasmodium falciparum. The earliest indications of incipient artemisinin
resistance may be a slowing of the rate at which parasites are cleared from the
blood following treatment. The Worldwide Antimalarial Resistance Network have
analysed data from 29,493 patients from 84 clinical trials in order to define the
nature and determinants of early parasite clearance following artemisinin-based
treatment in African populations. In doing so, they lay the foundation for
systems intended to enable the earliest possible detection of emerging
artemisinin resistance in Africa. Please see related article:
http://www.biomedcentral.com/1741-7015/13/212.
PMID- 26429336
TI - Age- and gender-dependent myocardial transcription patterns of cytokines and
extracellular matrix remodelling enzymes in cats with non-cardiac diseases.
AB - BACKGROUND: Age, gender and systemic diseases all influence cardiac function and
remodelling. In cats, age and gender associated myocardial remodelling and the
effect of systemic diseases on the myocardium have so far not been studied. The
aim of the study was therefore to investigate whether relevant cytokines and
extracellular matrix (ECM) remodelling enzymes are expressed in the myocardium of
cats with non-cardiac diseases and whether transcription levels are influenced by
age and gender. METHODS: The study was performed on myocardial samples from 26
cats aged between 2 and 19 years that had died with non-cardiac diseases.
Seventeen cats were female (2 entire) and nine were male (1 entire). Of these,
nine cats were diagnosed with diseases unlikely to affect the myocardium (control
cats). The remaining 17 cats suffered from diseases with likely systemic effects.
All hearts were assessed for any pathological changes, and the myocardium was
analysed for interleukin (IL)-1, -2, -4, -6, -18, tumour necrosis factor (TNF)
alpha, interferon (IFN)-gamma, transforming growth factor (TGF)-beta, matrix
metalloproteinase (MMP)-2, -3, -13, tissue inhibitor of MMP (TIMP)-1, -2 and -3
transcriptions using quantitative RT-PCR assays. RESULTS: Despite the absence of
any histological evidence of myocardial damage, inflammation and fibrosis, the
myocardium of all the cats was found to constitutively transcribe cytokines and
ECM remodelling enzymes, with generally higher mRNA concentrations in the atria
than in the ventricles. The young and male cats exhibited higher transcription
levels throughout the myocardium in comparison to the older and female cats.
Furthermore, age-associated transcription pattern differed between male and
female cats. CONCLUSION: The constitutive transcription of ECM remodelling
enzymes suggests continuous myocardial remodelling throughout the entire life of
a cat. The myocardium of young and male cats appears to be in a pro-inflammatory
state, whereas in older and female cats the myocardium exhibits a reduced
inflammatory reaction to systemic disease. Age-associated cardiac remodelling
seems to be influenced by non-hormonal factors in male and female cats.
PMID- 26429338
TI - Telepsychiatry intervention is better for ADHD symptoms than usual treatment
augmented by telemedicine consultation.
PMID- 26429337
TI - Qualitative analysis of patient-centered decision attributes associated with
initiating hepatitis C treatment.
AB - BACKGROUND: In this era of a constantly changing landscape of antiviral treatment
options for chronic viral hepatitis C (CHC), shared clinical decision-making
addresses the need to engage patients in complex treatment decisions. However,
little is known about the decision attributes that CHC patients consider when
making treatment decisions. We identify key patient-centered decision attributes,
and explore relationships among these attributes, to help inform the development
of a future CHC shared decision-making aid. METHODS: Semi-structured qualitative
interviews with CHC patients at four Veterans Health Administration (VHA)
hospitals, in three comparison groups: contemplating CHC treatment at the time of
data collection (Group 1), recently declined CHC treatment (Group 2), or recently
started CHC treatment (Group 3). Participant descriptions of decision attributes
were analyzed for the entire sample as well as by patient group and by gender.
RESULTS: Twenty-nine Veteran patients participated (21 males, eight females): 12
were contemplating treatment, nine had recently declined treatment, and eight had
recently started treatment. Patients on average described eight (range 5-13)
decision attributes. The attributes most frequently reported overall were:
physical side effects (83%); treatment efficacy (79%), new treatment drugs in
development (55%); psychological side effects (55%); and condition of the liver
(52%), with some variation based on group and gender. Personal life circumstance
attributes (such as availability of family support and the burden of financial
responsibilities) influencing treatment decisions were also noted by all
participants. Multiple decision attributes were interrelated in highly complex
ways. CONCLUSIONS: Participants considered numerous attributes in their CHC
treatment decisions. A better understanding of these attributes that influence
patient decision-making is crucial in order to inform patient-centered clinical
approaches to care (such as shared decision-making augmented with relevant
decision-making aids) that respond to patients' needs, preferences, and
circumstances.
PMID- 26429339
TI - Challenges in recruiting subjects to a pilot trial of patient-managed in-hospital
insulin.
AB - BACKGROUND: To examine the feasibility of implementing clinician-supported
inpatient self-managed insulin to aid in the planning of a randomized clinical
trial. RESULTS: We conducted a proof-of-concept interventional study of
inpatients with diabetes mellitus who had hospital orders for basal-bolus or
sliding scale insulin. Patients meeting inclusion criteria were offered the
opportunity to manage their own basal-bolus insulin with support from a diabetes
nurse practitioner. Over a three-month screening period, we conducted 361 screens
in 336 patients, only eleven of whom met all inclusion criteria. None of these
eleven eligible patients elected to enroll. The most common reason for refusal
was lack of interest in self-managing insulin while acutely ill (36 %).
DISCUSSION: Future studies of patient-managed in-hospital insulin should consider
enrolling less acutely ill patients with longer anticipated lengths of stay.
TRIALS REGISTRATION: NCT02144441.
PMID- 26429340
TI - In Memoriam: Patricia (Dr Pat) Charache, MD.
PMID- 26429341
TI - High Proportion of Asymptomatic Infections in an Outbreak of Hepatitis E
Associated With a Spit-Roasted Piglet, France, 2013.
AB - BACKGROUND: On 11 December 2013, 3 clustered cases of hepatitis E were reported
on a French coastal island. Individuals had taken part in a wedding meal that
included a spit-roasted piglet. The piglet had been stuffed with a raw stuffing
partly made from the liver. Investigations were carried out to identify the
vehicle of contamination and evaluate the dispersion of the hepatitis E virus
(HEV) in the environment. METHODS: A questionnaire was administered to 98 wedding
participants who were asked to give a blood sample. Cases were identified by
reverse transcription-polymerase chain reaction and serological tests. A
retrospective cohort study was conducted among 38 blood-sampled participants
after the exclusion of 14 participants with evidence of past HEV infection.
Relative risks (RR) and 95% confidence intervals were calculated based on food
consumed at the wedding meal using univariate and multivariable Poisson
regressions. Phylogenetic analyses were performed to compare the clinical HEV
strains. Strains were detected in the liquid manure sampled at the farm where the
piglet was born and in the untreated island wastewater. RESULTS: Seventeen cases
were identified, 70.6% were asymptomatic. Acute HEV infection was independently
associated with piglet stuffing consumption (RR = 1.69 [1.04-2.73], P = .03). Of
clinical strains from the index cases, veterinary and environmental HEV strains
were identical. CONCLUSIONS: Our investigation attributed this large HEV outbreak
to the consumption of an undercooked pig liver-based stuffing. After infection,
the cases became a temporary reservoir for HEV, which was detected in the
island's untreated wastewater.
PMID- 26429343
TI - Knee arthrodesis with modular nail after failed TKA due to infection.
AB - INTRODUCTION: Knee arthrodesis is an established procedure for limb salvage after
failed total knee arthroplasty (TKA) in cases of recurrent infection, soft tissue
damage, reduced bone stock or with a deficient extensor mechanism. Walking with
an arthrodesis is more efficient and less costly in terms of energy expenditure
than above-knee amputation. Surgical options include an arthrodesis nail,
external fixator or compression plate. We present our results of knee arthrodesis
using the modular Wichita Fusion Nail((r)) in patients after infected TKA.
METHODS: Fifteen patients with irretrievably failed TKA, due to infection, who
underwent arthrodesis with the Wichita Fusion Nail((r)) from 2004 to 2012 were
retrospectively reviewed to assess fusion rate, time to fusion, complication
rate, including new infections, and ambulatory status. RESULTS: Three patients
were lost to follow-up. Mean follow-up was 33 months (6-132 months). At their
most recent follow-up, all patients were walking with full weight bearing on a
fused arthrodesis. Mean time to union was 9 months (3-29 months). Three patients
necessitated a revision arthrodesis to achieve union after a mean of 5 months
after the last procedure. CONCLUSION: Arthrodesis with the Wichita Fusion
Nail((r)) provides satisfactory results in patients with failure after infected
TKA, with 75 % primary union rate and no new or persistent infection at last
follow-up visit. Although burdened with a high complication rate, it represents
an acceptable option for limb salvage in this particular pathology.
PMID- 26429345
TI - An Analog Filter Approach to Frequency Domain Fluorescence Spectroscopy.
AB - The rate equations found in frequency domain fluorescence spectroscopy are the
same as those found in electronics under analog filter theory. Laplace transform
methods are a natural way to solve the equations, and the methods can provide
solutions for arbitrary excitation functions. The fluorescence terms can be
modelled as circuit components and cascaded with drive and detection electronics
to produce a global transfer function. Electronics design tools such as SPICE can
be used to model fluorescence problems. In applications, such as remote sensing,
where detection electronics are operated at high gain and limited bandwidth, a
global modelling of the entire system is important, since the filter terms of the
drive and detection electronics affect the measured response of the fluorescence
signals. The techniques described here can be used to separate signals from fast
and slow fluorophores emitting into the same spectral band, and data collection
can be greatly accelerated by means of a frequency comb driver waveform and
appropriate signal processing of the response. The simplification of the analysis
mathematics, and the ability to model the entire detection chain, make it
possible to develop more compact instruments for remote sensing applications.
PMID- 26429342
TI - Antibacterial coating of implants in orthopaedics and trauma: a classification
proposal in an evolving panorama.
AB - Implanted biomaterials play a key role in current success of orthopedic and
trauma surgery. However, implant-related infections remain among the leading
reasons for failure with high economical and social associated costs. According
to the current knowledge, probably the most critical pathogenic event in the
development of implant-related infection is biofilm formation, which starts
immediately after bacterial adhesion on an implant and effectively protects the
microorganisms from the immune system and systemic antibiotics. A rationale,
modern prevention of biomaterial-associated infections should then specifically
focus on inhibition of both bacterial adhesion and biofilm formation.
Nonetheless, currently available prophylactic measures, although partially
effective in reducing surgical site infections, are not based on the pathogenesis
of biofilm-related infections and unacceptable high rates of septic
complications, especially in high-risk patients and procedures, are still
reported.In the last decade, several studies have investigated the ability of
implant surface modifications to minimize bacterial adhesion, inhibit biofilm
formation, and provide effective bacterial killing to protect implanted
biomaterials, even if there still is a great discrepancy between proposed and
clinically implemented strategies and a lack of a common language to evaluate
them.To move a step forward towards a more systematic approach in this promising
but complicated field, here we provide a detailed overview and an original
classification of the various technologies under study or already in the market.
We may distinguish the following: 1. Passive surface finishing/modification
(PSM): passive coatings that do not release bactericidal agents to the
surrounding tissues, but are aimed at preventing or reducing bacterial adhesion
through surface chemistry and/or structure modifications; 2. Active surface
finishing/modification (ASM): active coatings that feature pharmacologically
active pre-incorporated bactericidal agents; and 3. Local carriers or coatings
(LCC): local antibacterial carriers or coatings, biodegradable or not, applied at
the time of the surgical procedure, immediately prior or at the same time of the
implant and around it. Classifying different technologies may be useful in order
to better compare different solutions, to improve the design of validation tests
and, hopefully, to improve and speed up the regulatory process in this rapidly
evolving field.
PMID- 26429344
TI - The service impact of failed locking plate fixation of distal tibial fractures: a
service and financial evaluation at a major trauma centre.
AB - INTRODUCTION: The surgical treatment of distal tibial fractures is challenging
and controversial. Recently, locking plate fixation has become popular, but the
outcomes of this treatment are mixed with complication rates as high as 50 % in
the published literature. There are no reports specifically relating to the
financial and resource costs of failed treatment in the literature. METHOD:
Retrospective service analysis of patients who had undergone locking plate
fixation of a distal third tibial fracture between 2008 and 2011 with at least 12
months follow-up. Rates of readmission, reoperation, bony union and infection
were ascertained. The financial and resource (hospital stay and number of
outpatient appointments) implications of failed treatment were calculated.
RESULTS: Forty-two patients were identified. There were 31 type A fractures, one
type B fracture and 10 type C fractures. Three injuries were open. Twenty
patients were treated with minimally invasive percutaneous osteosynthesis (MIPO).
The readmission and reoperation rates were 26 % (n = 11) and 19 % (n = 8),
respectively. A total of 89 % of readmissions were due to infection. All patients
had received appropriate antibiotic regimens. The average costs of successful and
failed treatment were L 5538 and L 18,335, respectively. The average time to
union was 24.5 weeks. The rate of non-union was 21 % (n = 9). The rate of
infection was 28 % (n = 12), with all patients with open fracture incurring an
infection. Tourniquet time had no effect on the incidence of complications.
Smokers were more likely to incur a complication (p < 0.05), and non-union was
lower in the MIPO group (p < 0.05). The length and total cost of inpatient care
were significantly lower in the MIPO group (p < 0.05). MIPO patients were five
times less likely to incur readmission or reoperation. Failed treatment was three
times more expensive and four times longer than successful treatment. CONCLUSION:
The study identified a large burden to the service following failure of locking
plate treatment of these fractures, but the outcomes were similar to series
published in the literature. Readmission rates were high following these
injuries, and failed treatment was costly and had a significant impact on
hospital resources. The implementation of major trauma networks and centralised
subspecialised units should improve quality and value for money.
PMID- 26429346
TI - Making the case for a fracture liaison service: a qualitative study of the
experiences of clinicians and service managers.
AB - BACKGROUND: To develop services, healthcare professionals must make business
cases to managerial bodies within Hospital Trusts and if approved, to
commissioning bodies. Patients with hip fracture are at high risk of subsequent
fracture. To prevent this, guidance recommends structuring fracture prevention
services around coordinator based models. These are known as Fracture Liaison
Services (FLS). METHODS: 33 semi-structured qualitative interviews were conducted
with healthcare professionals with experience of making business cases for FLS.
Data was analysed thematically. RESULTS: Challenges in the development of
business cases included collecting all the relevant data and negotiating
compartmentalised budgets that impeded service development. Participants
described communication and cooperation between providers and commissioners as
variable. They felt financial considerations were the most important factor in
funding decisions, while improved quality of care was less influential. Other
factors included national guidelines and political priorities. The personalities
of clinicians championing services, and the clinical interests of commissioners
were seen to influence the decision-making process, suggesting that participants
felt that decisions were not always made on the basis of evidence-based care.
Effective strategies included ways of providing support, demonstrating potential
cost effectiveness and improved quality of care. Using a range of sources
including audit data collected on the successful Glasgow FLS, and improving
cooperation between stakeholders was advocated. Participants felt that the work
of commissioners and providers should be better integrated and suggested
strategies for doing this. CONCLUSIONS: This study provides information to
healthcare professionals about how best to develop business cases for FLS. We
conclude with recommendations on how to develop effective cases. These include
using guidance such as toolkits, aligning the aims of FLS with national
priorities and benchmarking services against comparators. Introducing a 'Local
Champion' to work alongside the service manager and establishing a multi
disciplinary working team would facilitate communication between stakeholders.
Involving commissioners in service design would help integrate the roles of
purchasers and providers.
PMID- 26429347
TI - Design of wireless multi-parameter monitoring system for oral feeding of
premature infants.
AB - Premature infants often cannot successfully and coordinately complete their oral
feeding. Mature sucking, swallowing, and respiration activities are crucial
indicators for the survival of newborn infants. Due to the vulnerability and
unobvious muscle activities of premature infants, current clinical care givers
mainly depend on the subjective behavioral observation of infants during oral
feeding. There is still lack of an integrated oral feeding monitoring system to
objectively and quantifiably monitor the related physiological parameters of
premature infants. In this study, a wireless multi-parameter monitoring system
for oral feeding of premature infants was proposed to monitor the sucking
swallowing-respiratory activities and the heart rate variability to provide
quantitative indices of oral feeding. Here, a novel sucking pressure sensing
module was also developed to monitor the premature infant's sucking pressure
under oral feeding to avoid the immersion influence of milk. The experimental
results showed that the proposed system detected the related physiological
parameters of premature infants during oral feeding effectively and may provide
an objective clinical evaluation tool for oral feeding ability and safety of
premature infants in the future.
PMID- 26429348
TI - An adaptive integrated algorithm for noninvasive fetal ECG separation and noise
reduction based on ICA-EEMD-WS.
AB - High-resolution fetal electrocardiogram (FECG) plays an important role in
assisting physicians to detect fetal changes in the womb and to make clinical
decisions. However, in real situations, clear FECG is difficult to extract
because it is usually overwhelmed by the dominant maternal ECG and other
contaminated noise such as baseline wander, high-frequency noise. In this paper,
we proposed a novel integrated adaptive algorithm based on independent component
analysis (ICA), ensemble empirical mode decomposition (EEMD), and wavelet
shrinkage (WS) denoising, denoted as ICA-EEMD-WS, for FECG separation and noise
reduction. First, ICA algorithm was used to separate the mixed abdominal ECG
signal and to obtain the noisy FECG. Second, the noise in FECG was reduced by a
three-step integrated algorithm comprised of EEMD, useful subcomponents
statistical inference and WS processing, and partial reconstruction for baseline
wander reduction. Finally, we evaluate the proposed algorithm using simulated
data sets. The results indicated that the proposed ICA-EEMD-WS outperformed the
conventional algorithms in signal denoising.
PMID- 26429349
TI - Detecting freezing of gait with a tri-axial accelerometer in Parkinson's disease
patients.
AB - Freezing of gait (FOG) is a common motor symptom of Parkinson's disease (PD),
which presents itself as an inability to initiate or continue gait. This paper
presents a method to monitor FOG episodes based only on acceleration measurements
obtained from a waist-worn device. Three approximations of this method are
tested. Initially, FOG is directly detected by a support vector machine (SVM).
Then, classifier's outputs are aggregated over time to determine a confidence
value, which is used for the final classification of freezing (i.e., second and
third approach). All variations are trained with signals of 15 patients and
evaluated with signals from another 5 patients. Using a linear SVM kernel, the
third approach provides 98.7% accuracy and a geometric mean of 96.1%. Moreover,
it is investigated whether frequency features are enough to reliably detect FOG.
Results show that these features allow the method to detect FOG with accuracies
above 90% and that frequency features enable a reliable monitoring of FOG by
using simply a waist sensor.
PMID- 26429350
TI - Combined treatment with parathyroid hormone (1-34) and beta-tricalcium phosphate
had an additive effect on local bone formation in a rat defect model.
AB - The objective of this study was to evaluate the effect of following combined
treatment with parathyroid hormone (1-34) (PTH) and beta-tricalcium phosphate
(beta-TCP) on local bone formation in a rat 3-mm critical-size defect at distal
femur. Twelve weeks after bilateral ovariectomy (OVX) and sham operation (sham),
all animals were randomly divided into four groups: group OVX, group OVX + beta
TCP, group sham, and group sham + beta-TCP, then all rats underwent bone defect
in the bilateral distal femurs, and beta-TCP were implanted into critical-sized
defects for group OVX + beta-TCP and group sham + beta-TCP. After defect
operation, all animals were received following subcutaneous injections with PTH
(60 MUg/kg, three times a week) until death at 4 and 8 weeks. The defected area
in distal femurs of rats was harvested for evaluation by histology, micro-CT, and
biomechanics. The results of our study show that systemic usage of PTH or local
usage of beta-TCP can increase the healing of defects in OVX or sham rats.
Furthermore, treatments with PTH and beta-TCP showed a stronger effect on
accelerating the local bone formation than used alone. Osteoporosis can limit the
function of PTH and/or beta-TCP. The results from our study demonstrate that
combination of PTH and beta-TCP had an additive effect on local bone formation in
non-osteoporosis and/or osteoporosis rats.
PMID- 26429351
TI - Numerical simulation of pharyngeal airflow applied to obstructive sleep apnea:
effect of the nasal cavity in anatomically accurate airway models.
AB - Repetitive brief episodes of soft-tissue collapse within the upper airway during
sleep characterize obstructive sleep apnea (OSA), an extremely common and
disabling disorder. Failure to maintain the patency of the upper airway is caused
by the combination of sleep-related loss of compensatory dilator muscle activity
and aerodynamic forces promoting closure. The prediction of soft-tissue movement
in patient-specific airway 3D mechanical models is emerging as a useful
contribution to clinical understanding and decision making. Such modeling
requires reliable estimations of the pharyngeal wall pressure forces. While nasal
obstruction has been recognized as a risk factor for OSA, the need to include the
nasal cavity in upper-airway models for OSA studies requires consideration, as it
is most often omitted because of its complex shape. A quantitative analysis of
the flow conditions generated by the nasal cavity and the sinuses during
inspiration upstream of the pharynx is presented. Results show that adequate
velocity boundary conditions and simple artificial extensions of the flow domain
can reproduce the essential effects of the nasal cavity on the pharyngeal flow
field. Therefore, the overall complexity and computational cost of accurate flow
predictions can be reduced.
PMID- 26429353
TI - suPAR: A Cardiac Biomarker With a Future?
PMID- 26429352
TI - The 2014 Atrial Fibrillation Guidelines Companion: A Practical Approach to the
Use of the Canadian Cardiovascular Society Guidelines.
AB - The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Guidelines Program
has generated a comprehensive series of documents regarding the management of
atrial fibrillation (AF) between 2010 and 2014. The guidelines provide evidence
based consensus management recommendations in a broad range of areas. These
guidelines have proven useful in informing clinical practice, but often lack
detail in specifications related to practical application, particularly for areas
in which the evidence base is limited or conflicting. Based on feedback from the
community, the CCS Atrial Fibrillation Guidelines Committee has identified a
number of areas that require clarification to address commonly asked practical
questions related to guidelines application. In the present article a number of
such questions are presented and suggestions about how they can be answered are
suggested. Among the issues considered are: (1) What duration of AF is clinically
significant? (2) How are the risk factors in the CCS Algorithm for selecting
anticoagulation therapy derived and defined? (3) How is valvular heart disease
defined and how do different forms of valve disease affect the choice of
anticoagulant therapy for AF patients? (4) How should we quantify renal
dysfunction and how does it affect therapeutic choices? The response to these
questions and the underlying logic are provided, along with an indication of
future research needed where no specific approach can presently be recommended
based on the literature.
PMID- 26429354
TI - Reduction in incidence of invasive fungal infection in patients receiving
allogeneic stem cell transplantation using combined diagnostic-driven approach
and itraconazole oral solution.
AB - Invasive fungal infections are an important cause of morbidity and mortality
after allogeneic haematopoietic stem cell transplantation. We evaluated, in our
allogeneic stem cell transplant patients, the effect on the incidence of invasive
fungal infection during neutropenia of a strategy combining a diagnostic-driven
approach with chemoprophylaxis during higher risk periods of graft vs. host
disease and prolonged neutropenia, using itraconazole oral solution with
parenteral voriconazole bridging. One hundred and thirty patients admitted for
allogeneic stem cell transplantation within two predefined 20 month periods were
included in the study. Data for all patients were collected prospectively.
Implementation of the protocol resulted in the administration of more
prophylactic antifungals to more patients. Following implementation, there was a
non-significant decrease in the overall number of invasive fungal infections
(IFI) [11 of 65 patients (17.2%) vs. 4 of 65 patients (6.2%, P = 0.051)], as well
as in the occurrence of invasive mould infections [8 of 65 patients (12.5%) vs. 2
of 65 patients (3.1%, P = 0.054)]. Survival rates at three and 6 months were not
significantly affected. A combined diagnostic-driven approach and antifungal
prophylaxis with oral itraconazole and an intravenous voriconazole bridging
protocol, was associated with a reduced, albeit non-statistically significant,
number of IFI in our medical centre.
PMID- 26429355
TI - Acute respiratory failure in patients with hematological malignancies: outcomes
according to initial ventilation strategy. A groupe de recherche respiratoire en
reanimation onco-hematologique (Grrr-OH) study.
AB - BACKGROUND: In patients with hematological malignancies and acute respiratory
failure (ARF), noninvasive ventilation was associated with a decreased mortality
in older studies. However, mortality of intubated patients decreased in the last
years. In this study, we assess outcomes in those patients according to the
initial ventilation strategy. METHODS: We performed a post hoc analysis of a
prospective multicentre study of critically ill hematology patients, in 17
intensive care units in France and Belgium. Patients with hematological
malignancies admitted for ARF in 2010 and 2011 and who were not intubated at
admission were included in the study. A propensity score-based approach was used
to assess the impact of NIV compared to oxygen only on hospital mortality.
RESULTS: Among 1011 patients admitted to ICU during the study period, 380 met
inclusion criteria. Underlying diseases included lymphoid (n = 162, 42.6 %) or
myeloid (n = 141, 37.1 %) diseases. ARF etiologies were pulmonary infections (n =
161, 43 %), malignant infiltration (n = 65, 17 %) or cardiac pulmonary edema (n =
40, 10 %). Mechanical ventilation was ultimately needed in 94 (24.7 %) patients,
within 3 [2-5] days of ICU admission. Hospital mortality was 32 % (123 deaths).
At ICU admission, 142 patients received first-line noninvasive ventilation (NIV),
whereas 238 received oxygen only. Fifty-five patients in each group (NIV or
oxygen only) were matched according the propensity score. NIV was not associated
with decreased hospital mortality [OR 1.5 (0.62-3.65)]. CONCLUSIONS: In
hematology patients with acute respiratory failure, initial treatment with NIV
did not improve survival compared to oxygen only. CLINICAL TRIAL: gov number NCT
01172132.
PMID- 26429356
TI - The effect of parenteral selenium on outcomes of mechanically ventilated patients
following sepsis: a prospective randomized clinical trial.
AB - BACKGROUND: Sepsis and septic shock is characterized by oxidative stress that
mainly promotes systemic inflammation and organ failure due to excessive free
radical production and depletion of antioxidant defenses. Therefore, we
investigated the effect of selenium administration on antioxidant status, levels
of cytokines and clinical outcomes. METHODOLOGY: This study was a prospective
randomized control trial (RCT) whereby patients received selenium as sodium
selenite (2 mg IV bolus followed by 1.5 mg continuous infusion for 14 days) plus
standard therapy. The control group received standard therapy without selenium.
The primary endpoint was 28-day mortality. The changes in the mean levels of
glutathione peroxidase (GPX) activity, IL-6, IL-8 and IL-10, the incidence of
ventilator-associated pneumonia (VAP) and other secondary endpoints were also
recorded. VAP was broken down into early VAP and late VAP to see the clinical
significance of each. We also recorded any adverse outcomes from selenium
infusion. RESULTS: Over 24-month period, 54 patients were recruited and
randomized and an intention to treat (ITT) principle was applied (selenium, n =
29; control, n = 25) in the final analysis. There was no statistically
significant difference between the two groups in 28-day mortality although it was
lower in the selenium group compared with the control group: 9 (31 %) in the
selenium versus 10 (40 %) in the control groups (p = 0.49). At day 0, GPX
activity was 0.185 +/- 0.3 versus 0.19 +/- 0.3 U/mL (p = 0.9), day 3, GPX
activity was 0.52 +/- 0.5 versus 0.17 +/- 0.2 U/mL (p = 0.02), at day 7 it was
0.55 +/- 0.5 versus 0.24 +/- 0.3 U/mL (p = 0.032), at day 10 it was 0.62 +/- 0.7
versus 0.33 +/- 0.4 U/mL (p = 0.048) and at day 14 it was 1.1 +/- 1 versus 0.89
+/- 1 U/mL (p = 0.70) for the selenium versus control groups, respectively.
However, there were no significant differences between the mean plasma levels of
all the three inflammatory cytokines at any point in time between the two groups.
There was a significant reduction in occurrence of VAP in the selenium group
compared with the control group (55.2 versus 84 %, p = 0.023), respectively.
CONCLUSION: High-dose selenium administration within the time frame of early goal
directed therapy was not resulted in reduction of 28-day mortality, but increased
the activity of glutathione peroxidase with no effect on the levels of
inflammatory cytokines at any point in time in mechanically ventilated septic
patients. However, selenium supplementation in mechanically ventilated patients
following sepsis was associated with reduced occurrence of VAP. TRIAL
REGISTRATION: IRCT201212082887N4 at WHO Clinical Trial Registry, August 29, 2014.
PMID- 26429357
TI - Trends in use and impact on outcome of empiric antibiotic therapy and non
invasive ventilation in COPD patients with acute exacerbation.
AB - BACKGROUND: Empiric antibiotic therapy is routinely prescribed in patients with
acute COPD exacerbations (AECOPD) requiring ventilatory support on the basis of
studies including patients conventionally ventilated. Whether this practice
remains valid to current management with first-line non-invasive ventilation
(NIV) is unclear. METHODS: In a cohort of ICU patients admitted between 2000 and
2012 for AECOPD, we analyzed the trends in empiric antibiotic therapy and in
primary ventilatory support strategy, and their respective impact on patients'
outcome. RESULTS: 440 patients admitted for 552 episodes were included; primary
NIV use increased from 29 to 96.7 % (p < 0.001), whereas NIV failure rate
decreased significantly (p = 0.004). In parallel, ventilator-associated pneumonia
(VAP) rate, VAP density and empiric antibiotic therapy use decreased (p = 0.037,
p = 0.002, and p < 0.001, respectively). These figures were associated with a
trend toward lower ICU mortality rate (p = 0.058). Logistic regression showed
that primary NIV use per se was protective against fatal outcome [odds ratios
(OR) = 0.08, 95 %CI 0.03-0.22; p < 0.001], whereas NIV failure, VAP occurrence,
and cardiovascular comorbidities were associated with increased ICU mortality [OR
= 17.6 (95 %CI 5.29-58.93), 11.5 (95 %CI 5.17-25.45), and 3 (95 %CI 1.37-6.63),
respectively]. Empiric antibiotic therapy was associated with decreased VAP rate
(log rank; p < 0.001), but had no effect on mortality (log rank; p = 0.793).
CONCLUSIONS: The sustained increase in NIV use allowed a decrease in empiric
antibiotic prescriptions in AECOPD requiring ventilatory support. Primary NIV use
and its success, but not empiric antibiotic therapy, were associated with a
favorable impact on patients' outcome.
PMID- 26429358
TI - Oncology health workers' views and experiences on caring for ethnic minority
patients: A mixed method systematic review.
AB - OBJECTIVES: To investigate what published research reveals about the views and
experiences of oncology health workers when caring for ethnic minority patients.
DESIGN: Systematic review of qualitative and quantitative studies. DATA SOURCES:
The following databases were systematically screened: PubMed, CINAHL, Web of
Science, and AnthroSource. Reference lists were checked for additional articles.
REVIEW METHODS: Empirical studies or systematic reviews (1/2000 to 12/2013) were
included if they concerned the oncology setting and the views or experiences of
healthcare workers and care users belonging to an ethnic or cultural minority
group. The methodological quality of each individual study was assessed using the
Critical Appraisal Skills Programme for Qualitative Studies and the Quality
Assessment Tool for Quantitative Studies. RESULTS: Eighteen publications met the
inclusion criteria. Thirteen articles had a qualitative, four a quantitative, and
one a mixed methods design. The results in the individual studies were
heterogeneous. Most studies reported challenges or barriers when caring for
ethnic minority patients, whereas fewer than half of the articles discussed
facilitating factors and opportunities. Oncology health workers participating in
the included studies sought to provide professional standards of care and tried
to adapt care to the needs of ethnic minority patients. However, they experienced
formidable communication barriers and they feared doing things that might be
considered culturally insensitive. The organizational aspects of care for the
oncology patient appeared to have a significant influence on how healthcare
providers view and experience oncology care for ethnic minority patients.
CONCLUSIONS: Views and experiences of participating oncology health workers were
characterized by a willingness to provide proper care for ethnic minority
patients, but this was hampered by a tangle of interrelated issues such as
linguistic barriers, fear and uncertainty, and assumptions about cultural
matters. Organizational aspects were shown to be a strong influence on healthcare
workers caring for ethnic minority patients. Due to methodological limitations of
the included studies, conclusions should be viewed with caution.
PMID- 26429359
TI - "Golden View" of the Porcine Wet Lab to Understand the Anatomy of the Mitral
Valve by Transesophageal Echocardiography.
PMID- 26429360
TI - Dexmedetomidine Attenuates Myocardial Injury in Off-Pump Coronary Artery Bypass
Graft Surgery.
AB - OBJECTIVE: To investigate the cardioprotective effect of the continuous
administration of dexmedetomidine using serum cardiac troponin I (cTnI) and
creatine kinase MB (CK-MB) concentrations as biomarkers during off-pump coronary
artery bypass grafting (OPCAB) surgery. DESIGN: A prospective, randomized,
parallel-group controlled study. SETTING: A university hospital. PARTICIPANTS:
One hundred sixteen patients undergoing OPCAB surgery. INTERVENTIONS: Patients
were divided randomly into 3 experimental groups that were separated by the
dexmedetomidine administration protocol: a high-dose group (loading dose, 1
MUg/kg; maintenance dose, 0.6 MUg/kg/h); low-dose group (loading dose, 0.6
MUg/kg; maintenance dose, 0.3 MUg/kg/h); and control group (the same amount of
0.9% saline as placebo). Serum cTnI and CK-MB levels were measured before surgery
and 24 hours and 48 hours after surgery. MEASUREMENTS AND MAIN RESULTS: Serum
cTnI and CK-MB levels in patients of the high-dose group were less than those of
the other 2 groups 48 hours after surgery. The administration of dexmedetomidine
significantly decreased the heart rate. Compared with the control group, there
was a significantly reduced requirement of sevoflurane in the other 2 groups
(p<0.05). The intraoperative and postoperative cumulative volumes of urine output
in the high-dose group were greater than those of the other 2 groups (p<0.05).
The authors also found that the extubation time and length of stay in the
intensive care unit were prolonged in the high-dose group. CONCLUSIONS:
Myocardial damage was reduced by the administration of a 1 MUg/kg loading dose
and a 0.6 MUg/kg/h infusion dose of dexmedetomidine. However, further studies are
needed to understand the underlying mechanism and to confirm that high doses of
dexmedetomidine could be administered safely in patients undergoing OPCAB
surgery.
PMID- 26429361
TI - Watermark Compression in Medical Image Watermarking Using Lempel-Ziv-Welch (LZW)
Lossless Compression Technique.
AB - In teleradiology, image contents may be altered due to noisy communication
channels and hacker manipulation. Medical image data is very sensitive and can
not tolerate any illegal change. Illegally changed image-based analysis could
result in wrong medical decision. Digital watermarking technique can be used to
authenticate images and detect as well as recover illegal changes made to
teleradiology images. Watermarking of medical images with heavy payload
watermarks causes image perceptual degradation. The image perceptual degradation
directly affects medical diagnosis. To maintain the image perceptual and
diagnostic qualities standard during watermarking, the watermark should be
lossless compressed. This paper focuses on watermarking of ultrasound medical
images with Lempel-Ziv-Welch (LZW) lossless-compressed watermarks. The watermark
lossless compression reduces watermark payload without data loss. In this
research work, watermark is the combination of defined region of interest (ROI)
and image watermarking secret key. The performance of the LZW compression
technique was compared with other conventional compression methods based on
compression ratio. LZW was found better and used for watermark lossless
compression in ultrasound medical images watermarking. Tabulated results show the
watermark bits reduction, image watermarking with effective tamper detection and
lossless recovery.
PMID- 26429362
TI - Negotiation and Decision Making with Collaborative Software: How MarineMap
'Changed the Game' in California's Marine Life Protected Act Initiative.
AB - Environmental managers and planners have become increasingly enthusiastic about
the potential of decision support tools (DSTs) to improve environmental decision
making processes as information technology transforms many aspects of daily life.
Discussions about DSTs, however, rarely recognize the range of ways software can
influence users' negotiation, problem-solving, or decision-making strategies and
incentives, in part because there are few empirical studies of completed
processes that used technology. This mixed-methods study-which draws on data from
approximately 60 semi-structured interviews and an online survey--examines how
one geospatial DST influenced participants' experiences during a multi-year
marine planning process in California. Results suggest that DSTs can facilitate
communication by creating a common language, help users understand the geography
and scientific criteria in play during the process, aid stakeholders in
identifying shared or diverging interests, and facilitate joint problem solving.
The same design features that enabled the tool to aid in decision making,
however, also presented surprising challenges in certain circumstances by, for
example, making it difficult for participants to discuss information that was not
spatially represented on the map-based interface. The study also highlights the
importance of the social context in which software is developed and implemented,
suggesting that the relationship between the software development team and other
participants may be as important as technical software design in shaping how DSTs
add value. The paper concludes with considerations to inform the future use of
DSTs in environmental decision-making processes.
PMID- 26429363
TI - Hydrological Responses to Land-Use Change Scenarios under Constant and Changed
Climatic Conditions.
AB - This study quantified the hydrological responses to land-use change scenarios in
the upper and middle Heihe River basin (HRB), northwest China, under constant and
changed climatic conditions by combining a land-use/cover change model (dynamic
conversion of land use and its effects, Dyna-CLUE) and a hydrological model (soil
and water assessment tool, SWAT). Five land-use change scenarios, i.e.,
historical trend (HT), ecological protection (EP), strict ecological protection
(SEP), economic development (ED), and rapid economic development (RED) scenarios,
were established. Under constant climatic condition, hydrological variations are
only induced by land-use changes in different scenarios. The changes in mean
streamflow at the outlets of the upper and the middle HRB are not pronounced,
although the different scenarios produce different outcomes. However, more
pronounced changes are observed on a subbasin level. The frequency of extreme
flood is projected to decrease under the SEP scenario, while under the other
scenarios, no changes can be found. Two emission scenarios (A1B and B1) of three
general circulation models (HadCM3, CGCM3, and CCSM3) were employed to generate
future possible climatic conditions. Under changed climatic condition,
hydrological variations are induced by the combination of land-use and climatic
changes. The results indicate that the impacts of land-use changes become
secondary when the changed climatic conditions have been considered. The
frequencies of extreme flood and drought are projected to decrease and increase,
respectively, under all climate scenarios. Although some agreements can be
reached, pronounced difference of hydrological responses can be observed for
different climate scenarios of different GCMs.
PMID- 26429364
TI - A Systematic Review of Acquired Left Ventricle to Right Atrium Shunts (Gerbode
Defects).
PMID- 26429365
TI - Applying Evidence-Based Medicine in Actual Clinical Practice: Can We Bridge the
Gap? A Review of the Literature.
PMID- 26429366
TI - Parenteral Anticoagulants in Acute Coronary Syndromes and Interventional
Cardiology: A Consensus Document.
PMID- 26429367
TI - Evaluation of Oxidative Stress Markers and Catecholamine Changes in Patients with
Dilated Cardiomyopathy Before and After Cardiopulmonary Exercise Testing.
AB - INTRODUCTION: The aim of this study was to evaluate oxidative stress markers
(OSM) and catecholamine levels in patients with dilated cardiomyopathy (DCM)
before and after cardiopulmonary exercise testing, and to investigate the
association between changes in these markers and the New York Heart Association
classification (NYHA) and left ventricular ejection fraction (LVEF) in these
patients. METHODS: We evaluated 74 patients with DCM and 80 control subjects
without DCM. Patients were grouped according to NYHA stages I/II or III/IV.
Eligible participants were considered to be those with LVEF values <45%. The OSM
analysed included superoxide dismutase (SOD), catalase (CAT), glutathione
reductase (GR), and glutathione peroxidase (GPX). The catecholamines analysed
included adrenaline, noradrenaline, and dopamine. Vitamin C was also evaluated.
All values were obtained before and after cardiopulmonary exercise testing.
RESULTS: There was a significant increase in GR, adrenaline, and noradrenaline
after testing in the DCM patients. A significant difference between controls and
patients in CAT and evaluated catecholamines was observed after testing. A
significant increase in GR, GPX, adrenaline, and noradrenaline for patients in
NYHA I/ II, and in CAT, GR, adrenaline, noradrenaline, and dopamine for patients
in NYHA III/IV, was found between the different times of observation. LVEF before
testing showed a significant positive correlation with GPX, and a negative
correlation with noradrenaline and adrenaline. After testing a significant
negative correlation was found with SOD and GR. CONCLUSIONS: The results of our
study demonstrate the complexity of the neurohumoral mechanisms and physiological
alterations in the failing heart in DCM patients. Further studies are needed,
including other biomarkers and larger samples of patients, in order to improve
our understanding of the aetiopathogenesis of DCM development and progression.
PMID- 26429368
TI - Studying Systemic Oxidative Stress in Heart Failure: Does It Have Any Role in
Clinical Practice?
PMID- 26429370
TI - Rheumatoid Arthritis and Atherosclerosis: Could Common Pathogenesis Translate
Into Common Therapies?
PMID- 26429369
TI - Effect of Long-Term TNF-alpha Inhibition with Infliximab on Left Ventricular
Torsion in Patients with Rheumatoid Arthritis.
AB - INTRODUCTION: We evaluated the impact of tumor necrosis factor alpha (TNF-alpha)
inhibition on left ventricular torsion (LVtor) in patients with rheumatoid
arthritis (RA) using speckle-tracking echocardiography (STE). METHODS: Thirty
eight RA patients without cardiovascular disease and 30 healthy subjects were
enrolled in the study. Twenty patients received infliximab, a monoclonal antibody
against TNF-alpha, and 18 patients received increasing doses of prednisolone for
180 days. Global systolic longitudinal strain (G-LS), global systolic radial
strain (G-RS) and global systolic circumferential strain (G-CS) were determined
by STE. LV basal and apical rotations from the base and apex were obtained and
used for calculation of LVtor. Pre-treatment LVtor levels were compared with
LVtor levels after therapy in both treatment groups. RESULTS: RA patients had
lower G-LS (-16.5 +/- 2.9; p<0.01), G-RS (37.6 +/- 1.5; p<0.01) and higher GCS (
23.6 +/- 3.5; p=0.04) compared with control subjects (-20.0 +/- 2.8, 40.7 +/-
4.8, -22.4 +/- 2.5, respectively; p<0.01). LVtor levels were significantly higher
in RA patients compared to controls (16.4 +/- 2.7 vs. 15.1 +/- 2.5; p=0.04),
which might be attributed to higher values of apical rotation (9.7 +/- 2.4 vs.
8.8 +/- 2.3; p=0.01). Patients treated with infliximab experienced a significant
decrease in LVtor (p=0.04), and a significant increase in G-LS (p<0.01) and G-RS
(p<0.01). No significant changes were observed among patients treated with
prednisolone. Percentage changes in LVtor were correlated with percent changes in
C-reactive protein CRP (r=0.58; p<0.01), disease activity score (r=0.78; p<0.01),
and G-LS (r=-0.40; p=0.04) in patients treated with infliximab. CONCLUSIONS: RA
is characterized by increased LVtor. Long term TNF-alpha inhibition improves LV
longitudinal and radial systolic deformation and decreases LVtor.
PMID- 26429371
TI - Aortic Flow Patterns After Simulated Implantation of Transcatheter Aortic Valves.
AB - INTRODUCTION: The functional behavior and hemodynamic characteristics of
percutaneously implanted bioprosthetic valves are not known. METHODS: We created
aortic models after the simulated implantation of two of the most widely used
bioprosthetic valves: the Edwards SAPIEN, and the Medtronic CoreValve. By using
computational fluid dynamics analysis we sought to investigate variations in the
aortic flow patterns induced by the two valve designs and their association with
detrimental phenomena such as vascular remodeling, vascular wall damage and
thrombosis. RESULTS: The simulated implantation of models that resemble the two
valves resulted in different aortic flow conditions. Vortex formation in the
upper ascending aorta was more persistent in the case of the simulated Medtronic
valve. The ranges of average wall shear stress (WSS) values were 2.4-3.5 Pa for
Edwards and 3.0-5.3 Pa for Medtronic; the calculated WSS values induced
endothelial quiescence and an atheroprotective setting in both valves. The
average shear stress on the simulated valve leaflets was low; however, hotspots
were present in both valves (155.0 Pa for Edwards and 250.0 Pa for Medtronic)
which would in theory be able to cause platelet activation and thus promote
thrombosis. The pressure drops along the aorta were slightly lower for the
Edwards compared to the Medtronic valve (198.0 Pa versus 218.0 Pa). CONCLUSIONS:
The presented method allows the assessment of aortic flow conditions following
the implantation of bioprosthetic valves. It may be useful in predicting
detrimental flow phenomena, thus facilitating the selection of appropriate valve
designs.
PMID- 26429372
TI - Are All Valves for All Aortas?
PMID- 26429373
TI - Fatty Myocardial Foci in Tuberous Sclerosis.
PMID- 26429374
TI - Myocardial Ischemia as an Indication for Surgical Intervention in Sinus Valsalva
Aneurysm.
PMID- 26429375
TI - Percutaneous Transvenous Retrieval of Intracardiac Port-A Catheter Using a Snare.
PMID- 26429376
TI - Giant Unruptured Left Sinus of Valsalva Aneurysm as an Unusual Cause of Ischemic
Heart Failure.
PMID- 26429377
TI - A Rare Case of Angiosarcoma of the Left Ventricle Detected by Cardiac Magnetic
Resonance Imaging.
PMID- 26429378
TI - Acute Coronary Syndromes and Anaemia.
PMID- 26429379
TI - The Need for More Research in Europe.
PMID- 26429380
TI - The state of critical care nursing education in Europe: an international survey.
PMID- 26429381
TI - Effects of a rapid infusion of 20% human serum albumin solution on acid-base
status and electrolytes in critically ill patients.
PMID- 26429382
TI - A new definition of biological effective dose: The dose distribution effects.
AB - A new biological effective dose (BED) is proposed in this note. This new BED
definition takes into account the fact that dose distribution is non-uniform for
tumors in patients' treatments. This new BED can be calculated from the dose
distribution within a tumor, making it practical and useful for clinical
applications.
PMID- 26429383
TI - GafChromic((r)) EBT3 films for patient specific IMRT QA using a multichannel
approach.
AB - PURPOSE: To evaluate EBT3 for pre-treatment patient specific quality assurance
(QA). The method we propose combines the experience gained in our center with the
guidelines of the protocol proposed by Lewis et al. in 2012. To compare the
multichannel approach with the single channel dosimetry. METHODS: Gafchromic(r)
EBT3 films were irradiated both at linac and TomoTherapy and calibration curves
were obtained. A series of irradiations with simple fields (uniform dose
distributions on regular shaped targets) was performed. In a second stage, films
were exposed to full clinical plans at linac (step and shoot IMRT and VMAT). At
TomoTherapy dose maps were obtained for a clinical plan in three different
coronal planes. Films were digitized using an Epson 10000XL scanner and FilmQATM
Pro software was employed for the analysis. RESULTS: The measured calibration
curves suggest that, at least for the two beams taken into account (6 MV linac
and TomoTherapy), a single calibration can be successfully adopted for each film
lot. The application of the multichannel optimization method strongly improves
the results in terms of gamma passing rates of the comparison between measured
and calculated maps. CONCLUSIONS: Up to now EBT films, although attractive, were
not preferred for routine patient specific QA due to their complex and time
consuming processing and to the challenging work of characterization. The
application of the mentioned protocol, together with some additional precautions,
and the adoption of the multichannel optimization dosimetry, make this detector a
handy and reliable tool for patient specific QA.
PMID- 26429384
TI - Sensitivity of a helical diode array dosimeter to Volumetric Modulated Arc
Therapy delivery errors.
AB - PURPOSE: To study the sensitivity of an ArcCHECK dosimeter in detecting delivery
errors during the delivery of Volumetric Modulated Arc Therapy (VMAT). METHODS:
Three types of errors in Multi Leaf Collimator (MLC) position and dose delivery
were simulated separately in the delivery of five prostate and five head and neck
(H&N) VMAT plans: (i) Gantry independent: a systematic shift in MLC position and
variation in output to the whole arc; (ii) Gantry dependent: sag in MLC position
and output variation as a function of gantry angle; (iii) Control point specific
MLC and output errors introduced to only a specific number of Control Points
(CP). The difference in local and global gamma (gamma) pass rate between the no
error and error-simulated measurements with 2%/2 mm and 3%/3 mm tolerances was
calculated to assess the sensitivity of ArcCHECK. The clinical impact of these
errors was also calculated. RESULTS: ArcCHECK was able to detect a minimum 3 mm
MLC error and 3% output error for Gantry independent errors using either local or
global gamma with 2%/2 mm tolerance. For the Gantry dependent error scenario a
minimum 3 mm MLC error and 3% dose error was identifiable by ArcCHECK using
either global or local gamma with 2%/2 mm tolerance. In errors introduced to
specific CPs a MLC error of 10 mm and dose error of 100% introduced to 4CPs were
detected by ArcCHECK. CONCLUSION: ArcCHECK used with either local or global gamma
analysis and 2%/2 mm criteria can be confidently used in the clinic to detect
errors above the stated error values.
PMID- 26429385
TI - Semi-automatic 3D segmentation of carotid lumen in contrast-enhanced computed
tomography angiography images.
AB - The atherosclerosis disease is one of the major causes of the death in the world.
Atherosclerosis refers to the hardening and narrowing of the arteries by plaques.
Carotid stenosis is a narrowing or constriction of carotid artery lumen usually
caused by atherosclerosis. Carotid artery stenosis can increase risk of brain
stroke. Contrast-enhanced Computed Tomography Angiography (CTA) is a minimally
invasive method for imaging and quantification of the carotid plaques. Manual
segmentation of carotid lumen in CTA images is a tedious and time consuming
procedure which is subjected to observer variability. As a result, there is a
strong and growing demand for developing computer-aided carotid segmentation
procedures. In this study, a novel method is presented for carotid artery lumen
segmentation in CTA data. First, the mean shift smoothing is used for uniformity
enhancement of gray levels. Then with the help of three seed points, the
centerlines of the arteries are extracted by a 3D Hessian based fast marching
shortest path algorithm. Finally, a 3D Level set function is performed for
segmentation. Results on 14 CTA volumes data show 85% of Dice similarity and 0.42
mm of mean absolute surface distance measures. Evaluation shows that the proposed
method requires minimal user intervention, low dependence to gray levels changes
in artery path, resistance to extreme changes in carotid diameter and carotid
branch locations. The proposed method has high accuracy and can be used in
qualitative and quantitative evaluation.
PMID- 26429386
TI - A new method to evaluate the residual activity in patients undergoing (131)I
thyroid therapy.
AB - The radioiodine administration is a standard therapeutic approach to both benign
thyroid diseases, such as hyperthyroidism, and carcinomas. The high administered
(131)I activities are of radiation protection concern, due to relevant patient
residual contamination. The aim of this work was to develop a new procedure based
on external radiometric surveys and on a mathematical model in order to estimate
the (131)I activity in patients undergoing hyperthyroidism radioiodine therapy.
In the first stage of this study, a suitable detector was chosen and its response
vs. activity was characterized. The experimental verification was performed
measuring the ambient dose equivalent rate from patients receiving radioiodine
administration. The results confirm the reliability of the proposed method, as
shown by the slight differences between the administered activities and the ones
calculated from external measurements. Furthermore, the same procedure was
applied to detect the percentage residual activity in patients at two preset time
intervals: 4 hours and 4 days after the radioiodine administration. The obtained
results clearly highlight that the method can ensure a level of reliability
compatible with the radiation protection purposes.
PMID- 26429388
TI - [The added value of robotic surgery].
AB - Robotic surgery has recently emerged as a feasible alternative to open and
laparoscopic procedures for the treatment of many urological diseases. The use of
robotics allows the surgeon to overcome the limitations of standard laparoscopy
while maintaining the advantages of a minimally invasive approach. Robotic
assisted radical prostatectomy is the most frequent surgery performed
robotically, resulting in better functional outcomes and comparable oncological
results with respect to open surgery. Given its advantages, the indications for
robotic surgery have progressively extended to different fields, and there is
increasing evidence for its effectiveness in high-risk prostate cancer, bladder
cancer, kidney cancer, and adrenal disease. Based on the available evidence in
the literature, robotic surgery should be considered a viable option for the
treatment of many urological conditions, with the final aim of optimizing
patients' outcomes.
PMID- 26429387
TI - Transposable elements and early evolution of sex chromosomes in fish.
AB - In many organisms, the sex chromosome pair can be recognized due to heteromorphy;
the Y and W chromosomes have often lost many genes due to the absence of
recombination during meiosis and are frequently heterochromatic. Repetitive
sequences are found at a high proportion on such heterochromatic sex chromosomes
and the evolution and emergence of sex chromosomes has been connected to the
dynamics of repeats and transposable elements. With an amazing plasticity of sex
determination mechanisms and numerous instances of independent emergence of novel
sex chromosomes, fish represent an excellent lineage to investigate the early
stages of sex chromosome differentiation, where sex chromosomes often are
homomorphic and not heterochromatic. We have analyzed the composition,
distribution, and relative age of TEs from available sex chromosome sequences of
seven teleost fish. We observed recent bursts of TEs and simple repeat
accumulations around young sex determination loci. More strikingly, we detected
transposable element (TE) amplifications not only on the sex determination
regions of the Y and W sex chromosomes, but also on the corresponding regions of
the X and Z chromosomes. In one species, we also clearly demonstrated that the
observed TE-rich sex determination locus originated from a TE-poor genomic
region, strengthening the link between TE accumulation and emergence of the sex
determination locus. Altogether, our results highlight the role of TEs in the
initial steps of differentiation and evolution of sex chromosomes.
PMID- 26429389
TI - [Robotic surgery in urology: the Italian contribution].
AB - The introduction of robotic technology has given a major boost to the urologic
surgery by expanding the indications of minimally-invasive surgery. The Italian
urological community has played a major role in this revolution, by contributing
to the development and dissemination of technological innovation in urology, with
several key publications stemming from this research. The most important
revolution has been observed in radical prostatectomy, with robotic technology
allowing to achieve better functional results. Nephron-sparing surgery has also
been expanded, and leading Italian centers are being involved in international
research groups focused on these topics. Major impact has been observed for
pyeloplasty, where Italy has been a leader in the field with the introduction of
robot-assisted single-site technique. In summary, the advent of robotics has
improved collaborations between Italy and other Countries, with increased
scientific activity, continuous improvement of surgical techniques and effective
training of young urologists.
PMID- 26429390
TI - [Positive surgical margin status after minimally invasive radical prostatectomy:
a multicenter study].
AB - UNLABELLED: The aim of our study is to evaluate the status of positive margins
(PSMs) comparing their incidence between aparoscopic radical prostatectomy (LRP)
and robot assisted radical prostatectomy (RARP) in centers with medium case-load
(50-150 cases/year). We also analyzed the correlations between surgical
technique, nerve-sparing approach (NS), and incidence of PSMs, stratifying our
results by pathological stage. MATERIALS AND METHODS: We analyzed 1992 patients
who underwent RP in various urologic centers. We evaluated the incidence of PSMs,
and then we compared the stage-related incidence of PSMs, for both the
techniques. RESULTS: We did not find a statistically significant difference
between the two surgical modalities in the study regarding the overall incidence
of PSMs. CONCLUSIONS: In our retrospective study, we did not find any difference
in terms of PSMs in RARP versus LRP. Our PSMs were not negligible, particularly
in pT3 stages, compared with high-volume centers; surgical experience and
patients' selection can be a possible explanation.
PMID- 26429391
TI - [Current status of robotic urologic surgery in Italy].
AB - The introduction of robot-assisted surgery represents a milestone in the history
of surgery. Today, many surgical disciplines make use of the DaVinci robotic
system in performing surgery, even complex ones. Italy stands as one of the
countries with a greater diffusion of robotics in surgery, particularly in
urological surgery. In Italy, every year, numerous urological surgeries are
performed with the DaVinci robot; however, costs of this technology are high and,
although likely to decrease, constitute a limit to the spread of the same and
restricting its use to shared areas.
PMID- 26429392
TI - [The robotic surgeon training].
AB - The widespread robotic surgery in the world highlighted the relevance of the
training programs for young urologists and residents. In the last years, urologic
societies and some independent robotic surgeons strongly worked to standardize
some general and specific training modules. Theoretical and practical sections of
robotic training programs have been recently specified. The role of simulators,
dry and wet laboratories, bedside assistance, and modular (step-by-step) training
at console represent the most relevant elements of robotic surgeon training.
Ideally, these didactic tools should be available in modern training centers. The
development of structured robotic training programs should be considered as one
of the priorities that the urologic community must take into account in the near
future.
PMID- 26429393
TI - Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus
Cystic Fibrosis on the Waitlist for Lung Transplantation.
AB - BACKGROUND: Survival in non-cystic fibrosis (CF) bronchiectasis is not well
studied. METHODS: The United Network for Organ Sharing database was queried from
1987 to 2013 to compare survival in adult patients with non-CF bronchiectasis to
patients with CF listed for lung transplantation (LTx). Each subject was tracked
from waitlist entry date until death or censoring to determine survival
differences between the two groups. RESULTS: Of 2112 listed lung transplant
candidates with bronchiectasis (180 non-CF, 1932 CF), 1617 were used for
univariate Cox and Kaplan-Meier survival function analysis, 1173 for multivariate
Cox models, and 182 for matched-pairs analysis based on propensity scores.
Compared to CF, patients with non-CF bronchiectasis had a significantly lower
mortality by univariate Cox analysis (HR 0.565; 95 % CI 0.424, 0.754; p < 0.001).
Adjusting for potential confounders, multivariate Cox models identified a
significant reduction in risk for death associated with non-CF bronchiectasis who
were lung transplant candidates (HR 0.684; 95 % CI 0.475, 0.985; p = 0.041).
Results were consistent in multivariate models adjusting for pulmonary
hypertension and forced expiratory volume in one second. CONCLUSIONS: Non-CF
bronchiectasis with advanced lung disease was associated with significantly lower
mortality hazard compared to CF bronchiectasis on the waitlist for LTx. Separate
referral and listing criteria for LTx in non-CF and CF populations should be
considered.
PMID- 26429394
TI - Knockdown of AKR1C3 exposes a potential epigenetic susceptibility in prostate
cancer cells.
AB - BACKGROUND: The aldo-keto reductase 1C3 (AKR1C3) has been heavily implicated in
the propagation of prostate malignancy. AKR1C3 protein is elevated within
prostate cancer tissue, it contributes to the formation of androgens and
downstream stimulation of the androgen receptor (AR). Elevated expression of
AKR1C3 is also reported in acute myeloid leukemia but the target nuclear
receptors have been identified as members of the peroxisome-proliferator
activated receptor (PPARs) subfamily. Thus, AKR1C3 cancer biology is likely to be
tissue dependent and hormonally linked to the availability of ligands for both
the steroidogenic and non-steroidogenic nuclear receptors. METHODS: In the
current study we investigated the potential for AKR1C3 to regulate the
availability of prostaglandin-derived ligands for PPARg mainly, prostaglandin J2
(PGJ2). Using prostate cancer cell lines with stably reduced AKR1C3 levels we
examined the impact of AKR1C3 upon proliferation mediated by PPAR ligands.
RESULTS: These studies revealed knockdown of AKR1C3 had no effect upon the
sensitivity of androgen receptor independent prostate cancer cells towards PPAR
ligands. However, the reduction of levels of AKR1C3 was accompanied by a
significantly reduced mRNA expression of a range of HDACs, transcriptional co
regulators, and increased sensitivity towards SAHA, a clinically approved histone
deacetylase inhibitor. CONCLUSIONS: These results suggest a hitherto unidentified
link between AKR1C3 levels and the epigenetic status in prostate cancer cells.
This raises an interesting possibility of a novel rational to target AKR1C3, the
utilization of AKRIC3 selective inhibitors in combination with HDAC inhibition as
part of novel epigenetic therapies in androgen deprivation therapy recurrent
prostate cancer.
PMID- 26429395
TI - Adipose-specific Vdr deletion alters body fat and enhances mammary epithelial
density.
AB - Vitamin D status has been associated with obesity, metabolic syndrome and several
cancers including colon and breast. Since adipocytes express VDR and obesity is a
known risk factor for cancer, vitamin D actions in adipose tissue may contribute
to its cancer protective effects. In the mammary gland, signaling from adipocytes
to epithelial cells is necessary for breast cancer initiation, but the impact of
vitamin D on this cross-talk is unclear. To examine the role of VDR in adipose
tissue, particularly in the context of the mammary gland, we crossed Vdr-flox
mice with Fabp4-cre mice to generate mice with adipose-specific Vdr deletion
(termed CVF mice). CVF mice and Fabp4-cre control mice (termed CN1 mice) were
reared on high calcium "rescue" diets (for comparison to global VDRKO mice) or on
high fat diets (to stimulate adiposity). Vdr expression was significantly reduced
in adipose tissue of CVF mice compared to CN1 mice. In contrast to global VDRKO
mice (which exhibit adipose atrophy), female CVF mice exhibited higher growth
rates and increased visceral fat pad weight compared to control mice. Expression
of Ucp1 and Pparg were elevated in white adipose tissue of CVF mice supporting
these genes as Vdr targets in mature adipocytes. Adipose-specific Vdr deletion
did not impair glucose tolerance or alter the weight of brown adipose tissue,
liver, pancreas or bone in response to high fat feeding. In contrast to the
effect of adipose-specific Vdr deletion on visceral fat pads, the weight of the
subcutaneous (mammary) fat pad was not increased in high fat fed CVF female mice
compared to control mice. Quantitative analysis of mammary ductal development on
whole mounts and H&E stained sections indicated that adipose-deletion of Vdr
significantly enhanced mammary epithelial density and branching. Collectively,
these data support the hypothesis that Vdr in mature adipocytes alters the
metabolic response to high fat diets and exerts anti-proliferative effects on the
mammary epithelium.
PMID- 26429396
TI - Biological evaluation of new vitamin D2 analogues.
AB - 1,25-dihydroxyvitamin D3 (1,25D), a steroid hormone which regulates
calcium/phosphate homeostasis, has a broad spectrum of anti-cancer activities,
including differentiation of acute myeloid leukemia (AML) cells. In order to
avoid undesirable side effects such as hypercalcemia, low-calcemic analogues
should be produced for therapeutic purposes. In this paper, we describe
biological activities of double-point modified analogues of vitamin D2 and we
compare them to 1,25D and to paricalcitol, the drug used to treat secondary
hyperparathyroidism. In vivo, our new analogues have lower calcemic effects, and
lower toxicity in comparison to 1,25D. They have enhanced pro-differentiating and
transcription-inducing activities in AML cells. Interestingly, differentiation
effects do not correlate with the affinities of the analogues to the vitamin D
receptor (VDR).
PMID- 26429397
TI - Amplification of lipotoxic cardiomyopathy in the VDR gene knockout mouse.
AB - Previous studies demonstrated that the liganded vitamin D receptor (VDR) plays an
important role in controlling cardiovascular homeostasis. Both the whole animal
VDR gene knockout (VDR-/-) and the myocyte-specific VDR gene deletion result in
changes in cardiac structure and function. Clinical states associated with
cardiac steatosis (obesity and diabetes mellitus) are also associated with low
circulating 25 OH vitamin D levels. We, therefore, examined the effects of VDR
deficiency (VDR-/- mouse) in a murine model of cardiac steatosis that expresses
the terminal enzyme involved in triglyceride synthesis, diacylglycerol
acyltransferase 1 (DGAT1), selectively in the cardiac myocyte. These mice display
early cardiac dysfunction and late cardiomyopathy and heart failure. In the
present study, we demonstrate that mice harboring both genetic modifications
(i.e., MHC-DGAT1 Tg and VDR-/-) exhibit an increase in myocyte size, heart
weight/body weight ratio and natriuretic peptide gene expression, all markers of
cardiac hypertrophy, that exceed that seen in either VDR-/- or the MHC-DGAT1 Tg
mice alone. This was accompanied by a dramatic increase in interstitial fibrosis
and increased expression of collagen 1a1 and collagen 3a1, as well as the
osteopontin and matrix metalloproteinase 2, genes. At a functional level, this
resulted in a 37% reduction in ejection fraction and 55% reduction in fractional
shortening in the DGAT1; VDR-/- mice relative to the controls. Collectively,
these data demonstrate that deficiency in the vitamin D signaling system enhances
the pathological phenotype in this experimental cardiomyopathy and suggest an
important role for vitamin D in modulating disease severity in common
cardiovascular disorders.
PMID- 26429398
TI - St. Gallen endocrine response classes predict recurrence rates over time.
AB - BACKGROUND: In 2007 the St. Gallen consensus panel defined three endocrine
response classes: highly endocrine responsive (ER-H), incomplete endocrine
responsive (ER-I) and non-endocrine responsive tumours (ER-N). However, it is
uncertain whether ER-I tumours are less responsive than ER-H tumours. We
investigated whether recurrence rates vary over time between response classes.
Additionally, we investigated the most predictive response class definition for
tamoxifen benefit. PATIENTS AND METHODS: We recollected tumours from 646 patients
who participated in a randomized trial of adjuvant tamoxifen vs. OBSERVATION:
Estrogen receptor (ER), progesterone receptor (PgR), HER2 status and tumour grade
were revised centrally. St. Gallen classes were evaluated for recurrence free
interval (RFI). Change in hazards over time was assessed. Subsequently, 6
alternative response class definitions were compared to optimize the cut-off for
PgR and ER. RESULTS: Schoenfeld residuals indicate a failure of proportional
hazards between the endocrine response groups (p = 0.0001). The HR for recurrence
risk shifted over time with the ER-H group initially being at lower risk (HR ER-H
vs. ER-I 0.5), but after six years the recurrence risk increased (HR 1.9). The
cut-off values for ER and PgR that statistically best discriminated RFI in the
first 4 years for lymph node positive patients were ER >= 50% and PgR >= 75%.
CONCLUSION: We demonstrated a marked variability in endocrine therapy benefit.
Patients with ER-H tumours have a larger benefit during adjuvant tamoxifen and in
the first years after accomplishing of the therapy, but suffer from late
recurrences. This might have implications for optimal treatment duration.
PMID- 26429399
TI - Technical innovation in adjuvant radiotherapy: Evolution and evaluation of new
treatments for today and tomorrow.
AB - Recent innovations in breast cancer radiotherapy include intensity modulated
radiotherapy, brachytherapy and intraoperative radiotherapy and current trials
are seeking to evaluate their value in optimizing local control while maintaining
cosmetic effects. Future clinical dividends in local control and survival may
come from the identification of molecular signatures of breast cancer
radiosensitivity, the development of predictive signatures and identification of
immunohistochemical markers of risk of local recurrence. The importance of tumour
heterogeneity is being increasingly recognized as an important factor in
determining radiotherapy response and an improved understanding of the biology of
the tumour microenvironment may identify targets that allow enhanced
radiosensitisation or reversal of radioresistance when inhibited. This review
describes recent developments in these areas.
PMID- 26429400
TI - Should we offer prenatal testing for 17q12 microdeletion syndrome to all cases
with prenatally diagnosed echogenic kidneys? Prenatal findings in two families
with 17q12 microdeletion syndrome and review of the literature.
AB - OBJECTIVE: The objective of this study is to report the prenatal ultrasound scan
findings in four fetuses from two families postnatally diagnosed with 17q12
microdeletion syndrome on microarray CGH and review the literature. METHODS: We
report two families presenting with prenatally detected hyperechogenic kidneys.
In family 1, the mother had three pregnancies complicated by anhydramnios with
bilateral hyperechogenic kidneys, hyperechogenic enlarged cystic kidneys, and
bilateral hyperechogenic kidneys with polyhydramnios respectively. In family 2,
prenatal ultrasound scans detected hyperechogenic kidneys. A pubmed search for
all reported cases of 17q12 deletion between 2005 and 2015 was performed. All
publications were reviewed, and findings summarised. RESULTS: Fourteen
publications were deemed suitable for literature review; there was a diagnosis of
17q12 deletion with documented prenatal findings in 25 cases. Prenatal renal
anomalies were reported in 88% of these cases. Anomalies were documented from 15
weeks, and most common presentation was hyperechogenic, muticystic, or enlarged
kidneys. Both oligohydramnios and polyhydramnios were seen. Postnatal renal
ultrasound scan findings were of muticystic or multicystic dysplastic kidney.
There did not appear to be correlation of prenatal presentation and severity of
renal disease. CONCLUSION: Prenatal testing should be offered to all cases of
hyperechogenic kidneys, with unknown cause.
PMID- 26429401
TI - Cardiovascular disease and mortality in patients with type 2 diabetes after
bariatric surgery in Sweden: a nationwide, matched, observational cohort study.
AB - BACKGROUND: In patients with diabetes and obesity specifically, no studies have
examined mortality after bariatric surgery. We did a nationwide study in Sweden
to examine risks of cardiovascular disease and mortality in patients with obesity
and diabetes who had undergone bariatric surgery (Roux-en-Y gastric bypass
[RYGB]). METHODS: In this nationwide, matched, observational cohort study, we
merged data for patients who had undergone RYGB registered in the Scandinavian
Obesity Surgery Registry with other national databases, and identified matched
controls (on the basis of sex, age, BMI, and calendar time [year]) who had not
undergone bariatric surgery from the National Diabetes Registry. We assessed
risks of cardiovascular disease and death using a Cox proportional-hazards
regression model and other methods to examine the treatment effect while
accounting for residual confounding. Primary outcomes were total mortality,
cardiovascular death, and fatal or non-fatal myocardial infarction. FINDINGS:
Between Jan 1, 2007, and Dec 31, 2014, we obtained data for 6132 patients who had
undergone RYGB and 6132 control patients who had not. Median follow-up was 3.5
years (IQR 2.1-4.7). We noted a 58% relative risk reduction (hazard ratio [HR]
0.42, 95% CI 0.30-0.57; p<0.0001) in overall mortality in the RYGB group compared
with the controls. The risk of fatal or non-fatal myocardial infarction was 49%
lower (HR 0.51, 0.29-0.91; p=0.021) and that of cardiovascular death was 59%
lower (0.41, 0.19-0.90; p=0.026) in the RYGB group than in the control group. 5
year absolute risks of death were 1.8% (95% CI 1.5-2.2) in the RYGB group and
5.8% (5.0-6.8) in the control group. INTERPRETATION: Our findings provide support
for the benefits of RYGB surgery for patients with obesity and type 2 diabetes.
The causes of these beneficial effects may be the weight reduction per se,
changes in physiology and metabolism, improved care and treatment, improvements
in lifestyle and risk factors, or combinations of these factors. FUNDING: Swedish
Association of Local Authorities and Regions and Region Vastra Gotaland.
PMID- 26429403
TI - Weight loss surgery and cardiovascular risk and mortality in patients with type 2
diabetes.
PMID- 26429402
TI - Reduction of cardiovascular risk in chronic kidney disease by mineralocorticoid
receptor antagonism.
AB - Cardiovascular disease is the leading cause of death and morbidity in people with
chronic kidney disease, but there are few evidence-based treatments for reducing
cardiovascular events in these patients. The failure of novel drug candidates to
delay progression to end-stage renal disease and limit or abrogate cardiovascular
morbidity and mortality has led to increased interest in a mineralocorticoid
receptor (MR) antagonist-based treatment model to reduce cardiovascular risk in
patients with chronic kidney disease and end-stage renal disease. Aldosterone
concentrations and MR signalling are associated with an enhanced risk of
cardiovascular injury and the incidence of sudden death, and MR blockade
decreases the risk of cardiovascular events and sudden death in patients with
reduced glomerular filtration rate. Since evidence from clinical trials shows
that treatment with MR antagonists confers a morbidity and mortality advantage
for patients with cardiovascular disorders, similar benefits might also accrue in
patients with chronic kidney disease. Large prospective trials are urgently
needed to answer this question. In this Review, I argue that despite differences
in the pathophysiology and clinical features of cardiovascular disease in
patients with and without chronic kidney disease, MR antagonists could provide
cardiovascular benefit in patients with chronic kidney disease.
PMID- 26429404
TI - Dead Space Management After Orthopaedic Trauma: Tips, Tricks, and Pitfalls.
AB - Dead space is defined as the residual tissue void after tissue loss. This may
occur due to tissue necrosis after high-energy trauma, infection, or surgical
debridement of nonviable tissue. This review provides an update on the state of
the art and recent advances in the management of osseous and soft tissue defects.
Specifically, our focus will be on the initial dead space assessment, provisional
management of osseous and soft tissue defects, techniques for definitive
reconstruction, and dead space management in the setting of infection. LEVEL OF
EVIDENCE: Therapeutic Level V. See Instructions for Authors for a complete
description of levels of evidence.
PMID- 26429405
TI - Significant differences between local reporting and central assessment of
radiological complications in a prospective, multicenter study about locking
plate fixation of proximal humerus fractures.
AB - OBJECTIVES: To compare radiological complication reporting outcomes undertaken by
an independent review board and the responsible on-site study personnel in a
multicenter study about locking plate fixation of proximal humeral fractures.
DESIGN: prospective, multicenter study SETTING:: Level I trauma centers
PATIENTS:: One-hundred and fifty patients with a radiological confirmed, closed,
displaced proximal humeral fracture fixed with a locking plate and aged between
fifty and ninety years. INTERVENTION: Re-evaluation of all radiological data
according to pre-defined criteria after finished collection of all study
radiographs by an independent review board. MAIN OUTCOME MEASUREMENTS:
Differences in outcomes between the review board and the sites assessment were
tested with a paired t-test. Inter-rater agreements between the central review
board and sites assessments were estimated by means of kappa statistics. RESULTS:
The review board revealed significant more radiological complications than the
sites assessment (p = 0.006), except for the complication 'head necrosis'. The
inter-rater agreement was slight to moderate in all calculated categories.
CONCLUSIONS: To prevent underreporting of radiological complications by on-site
assessment, the implementation of a complication review board, using pre-defined
criteria, is recommended for clinical studies that focus on radiological
complications.
PMID- 26429406
TI - What Is the Role of Vitamin D Supplementation in Acute Fracture Patients? A
Systematic Review and Meta-Analysis of the Prevalence of Hypovitaminosis D and
Supplementation Efficacy.
AB - OBJECTIVES: The objectives of this systematic review and meta-analyses are (1) to
estimate the prevalence of hypovitaminosis D in fracture patients and (2) to
summarize the available evidence on the efficacy of vitamin D supplementation in
fracture patients. DATA SOURCES: A comprehensive search of the MEDLINE, Embase,
PubMed, and Cochrane Central Register of Controlled Trials databases was
conducted. Conference abstracts from relevant meetings were also searched. STUDY
SELECTION: We included studies that investigate vitamin D insufficiency or
examine the effect of vitamin D supplementation on 25-hydroxy-vitamin D (25(OH)D)
serum levels in fracture patients. DATA EXTRACTION: Two authors independently
extracted data using a predesigned form. DATA SYNTHESIS: We performed a pooled
analysis to determine the prevalence of postfracture hypovitaminosis D and mean
postfracture 25(OH)D levels. We present detailed summaries of each of the studies
evaluating the impact of vitamin D supplementation. RESULTS: The weighted pooled
prevalence of hypovitaminosis D was 70.0% (95% confidence interval: 63.7%-76.0%,
I = 97.7). The mean postfracture serum 25(OH)D was 19.5 ng/mL. The studies that
evaluated the efficacy of vitamin D supplementation suggest that vitamin D
supplementation safely increases serum 25(OH)D levels. Only 1 meeting abstract
showed a trend toward reduced risk of nonunion after a single large loading dose
of vitamin D. CONCLUSIONS: This review found a high prevalence of hypovitaminosis
D in fracture patients and that vitamin D supplementation at a range of doses
safely increases 25(OH)D serum levels. To date, only 1 pilot study published as a
meeting abstract has demonstrated a trend toward improved fracture healing with
vitamin D supplementation. LEVEL OF EVIDENCE: Prognostic Level II. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 26429407
TI - Surgical Treatment of Femoral Neck Fractures After 24 Hours in Patients Between
the Ages of 18 and 49 Is Associated With Poor Inpatient Outcomes: An Analysis of
1361 Patients in the National Trauma Data Bank.
AB - OBJECTIVE: To determine (1) the incidence of delayed surgical treatment, (2) risk
factors associated with delayed surgical intervention, (3) inpatient adverse
events and discharge disposition, and (4) the association of delayed surgery with
inpatient adverse events. DESIGN: Retrospective cohort study. SETTING: 2011 and
2012 National Trauma Data Bank. PATIENTS/PARTICIPANTS: All adult patients younger
than 50 years of age with femoral neck fractures. INTERVENTION: Not applicable.
MAIN OUTCOME MEASURES: (1) Time to surgical intervention after inpatient
admission, (2) odds ratio (OR) for delayed surgery (later than 24 hours after
admission), (3) incidence of inpatient adverse events and discharge disposition,
(3) rates of inpatient adverse events and discharge disposition, and (4) OR for
occurrence of serious adverse events, minor adverse events, and any adverse
events. RESULTS: Of a total of 1361 patients, 67.8% of patients underwent surgery
within 24 hours of presentation. In multivariate analysis (controlling for
patient and injury characteristics), Charlson comorbidity index of 3+ compared
with Charlson comorbidity index of 0 (OR: 3.62), pelvic fracture (OR: 2.01), and
treatment at an American College of Surgeons level I trauma center (compared with
levels II-IV; OR: 1.56) were associated with delayed surgery. The overall rate of
mortality and inpatient adverse events was 0.2% and 12.1%, respectively. Delayed
surgery was independently associated with increased occurrence of serious adverse
events, minor adverse events, and any adverse events. CONCLUSIONS: Although a
majority of nonelderly patients with femoral neck fractures underwent surgery
within the first 24 hours of admission and had good outcomes in the short-term,
certain subpopulations have a higher risk of delayed surgery. As delayed surgery
is associated with worse outcomes, and short-term and long-term outcomes, efforts
should focus on expediting care of these patients. LEVEL OF EVIDENCE: Prognostic
Level II. See Instructions for Authors for a complete description of levels of
evidence.
PMID- 26429408
TI - Are Locking Constructs in Distal Femoral Fractures Always Best? A Prospective
Multicenter Randomized Controlled Trial Comparing the Less Invasive Stabilization
System With the Minimally Invasive Dynamic Condylar Screw System.
AB - OBJECTIVES: The purpose of this clinical study is to determine whether the rate
of fracture healing and fracture union, repaired with a locked device, will be as
good as or better than standard nonlocking bicortical fixation in distal femoral
fractures. DESIGN: Institutional review board-approved, multicenter prospective
randomized controlled trial. SETTING: Seven level 1 trauma centers across Canada.
PATIENTS: Fifty-two patients with distal femoral fractures (AO/OTA 33A1 to 33C2)
were enrolled in the randomized trial. Twelve AO/OTA 33C3 fractures were excluded
from the randomized trial but followed up as a nonrandomized cohort.
INTERVENTION: Patients were treated through a standardized minimally invasive
approach. Fractures were randomized 1:1 to treatment with the locked Less
Invasive Stabilization System (LISS; Synthes, Paoli, PA) or the dynamic condylar
screw (DCS). The nonrandomized cohort was treated at the surgeon's discretion.
MAIN OUTCOME MEASUREMENTS: Primary outcomes were time to radiological union and
number of delayed/nonunions at 12 months. Secondary outcomes were postoperative
function and complications. RESULTS: Fifty-two patients were randomized including
34 women and 18 men. The mean age was 59 years. Twenty-eight patients were
treated with the LISS and 24 with the DCS. There was no statistically significant
difference between the LISS and the DCS in terms of the number of fractures
healed, time to union, or functional scores. Complications and revisions were
more common in the LISS group. There were 7 reoperations in the LISS group and
one in the DCS group. Only 52% of the LISS group healed without intervention by
12 months compared with 91% in the DCS group. CONCLUSIONS: There was no advantage
to the locking plate design in the management of distal femoral fractures in this
study. The higher cost of the locking plates, challenges in technique, and lack
of superiority have led the authors to discontinue the use of this lateral
unicortical locking device in favor of other devices that allow locked or
nonlocked bicortical fixation, articular compression, and bridging of the
comminuted fracture segments. The cost-effective treatment for a subgroup or
periarticular fractures may be a fixed-angle nonlocked device in patients with
reasonable bone quality. LEVEL OF EVIDENCE: Therapeutic Level II. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 26429409
TI - Metabolism of kurarinone by human liver microsomes and its effect on
cytotoxicity.
AB - CONTEXT: Kurarinone, the most abundant prenylated flavonoid in Sophora flavescens
Aiton (Leguminosae), is a promising antitumor therapeutic. However, it shows
significant hepatotoxicity. Furthermore, how kurarinone is metabolized in humans
remains unclear. OBJECTIVE: The objective of this study is to investigate
kurarinone metabolism in human liver microsomes (HLMs) and the role of metabolism
in kurarinone-induced cytotoxicity. MATERIALS AND METHODS: The UDP
glucuronosyltransferase isoforms (UGTs) involved in kurarinone glucuronidation
were identified using chemical inhibitors (100-1000 uM phenylbutazone; 10-100 uM
beta-estradiol; 10-100 uM 1-naphthol; 10-500 uM propofol; and 100-1000 uM
fluconazole) and recombinant human UGTs. Kurarinone (2-500 uM) was incubated with
HLMs and UGTs (0.5 mg/mL) for 15 min to determine enzyme kinetic parameters. The
IC50 value of kurarinone (10-200 uM) was evaluated in a HLMs/3T3 cell co-culture
system. RESULTS: Kurarinone is extensively converted to two glucuronides (M3 and
M4) in HLMs. M3 formation was catalyzed by multiple UGT1As, with UGT1A3 showing
the highest intrinsic clearance (120.60 mL/min/mg). M4 formation was catalyzed by
UGT1A1, UGT2B4, and UGT2B7. UGT1A1 showed the highest intrinsic clearance (60.61
mL/min/mg). The kinetic profiles of the five main UGTs and HLMs fit substrate
inhibition kinetics, with Km values ranging from 5.20 to 46.52 uM, Vmax values
ranging from 0.20 to 3.06 umol/min/mg, and Ksi values ranging from 25.58 to
230.30 uM. The kurarinone IC50 value was 93 MUM in the control group, 102 MUM in
HLMs with NADPH, and 160 MUM in HLMs with UDPGA. DISCUSSION AND CONCLUSION:
Kurarinone glucuronidation is a detoxification pathway. This information may help
to elucidate the risk factors regulating kurarinone toxicity.
PMID- 26429410
TI - Molecular and functional identification of three interleukin-17A/F (IL-17A/F)
homologues in large yellow croaker (Larimichthys crocea).
AB - The interleukin-17 (IL-17) cytokine family plays a central role in the
coordination of inflammatory responses. In fish species, three genes that have a
similar homology to both IL-17A and IL-17F were designated IL-17A/F1, 2, and 3.
In this study, we identified three IL-17A/F homologues (LycIL-17A/F1, 2, and 3)
from large yellow croaker (Larimichthys crocea). The deduced LycIL-17A/F1 and 3
had four cysteine residues conserved in teleost IL-17A/F1 and 3 homologues and
shared a domain similar to the B chain of human IL-17F. The deduced LycIL-17A/F2
possessed the unique arrangement of six cysteine residues as teleost IL-17A/F2
(except Fugu IL-17A/F2) and higher vertebrate IL-17A and F, and shared a domain
similar to the D/E chain of human IL-17A. Phylogenetic analysis showed that
teleost IL-17A/F1 and 3 fall into a major clade, whereas IL-17A/F2 forms a
separated clade and is clustered with IL-17N. Based on structural and
phylogenetic analyses, we suggest that teleost IL-17A/Fs may be classified into
two subgroups: one consisting of IL-17A/F1 and 3, and the other composed of IL
17A/F2. The three LycIL-17A/Fs were constitutively expressed in all tissues
examined although at a different level. Following challenge with Aeromonas
hydrophila, expression of these three LycIL-17A/Fs was rapidly increased in head
kidney and gills. The in vivo assays showed that recombinant LycIL-17A/F1, 2, and
3 all were able to enhance the expression of pro-inflammatory cytokines (IL
1beta, IL-6, and TNF-alpha2), chemokines (CXCL8 and CXCL13), and antimicrobial
peptide hepcidin in head kidney. Furthermore, LycIL-17A/Fs appeared to mediate
pro-inflammatory responses via NF-kappaB signalling. These results therefore
reveal similar functions between the two subgroup members,LycIL-17A/F1 and 3 and
LycIL-17A/F2, in promoting inflammation and host defences.
PMID- 26429412
TI - Identification of a CD4 variant in Microminipigs not detectable with available
anti-CD4 monoclonal antibodies.
AB - The Microminipig is an extra-small sized novel miniature pig developed in Japan.
In the process of peripheral blood mononuclear cells analysis by flow cytometry,
CD4+ cells could not be detected in some pigs with an anti-pig CD4 antibody
(clone 74-12-4), or in some pigs with two other antibodies from different clones
(MIL17 and PT90A). In a herd of 178 Microminipigs, 87 pigs (48.9%) were reactive
with the anti-CD4 antibody (designated as CD4.A), and 91 pigs (51.1%) were non
reactive (designated as CD4.B). The CD4 types of piglets delivered from parents
with CD4.A were CD4.A or CD4.B, and piglets delivered from parents with CD4.B
were only CD4.B. This implies that the CD4.A pigs were homozygous for CD4.A or
heterozygous for CD4.A and CD4.B, and the CD4.B pigs were homozygous for CD4.B.
The CD4.B trait might be recessive. Significant differences could not be found in
the percentage of CD3+ and CD8+ cells in whole lymphocytes between CD4.A and
CD4.B animals. In the profile of CD4.B pigs, CD4+CD8+ T cells appeared to be
detected in the CD4-CD8+ T cell region because the CD8 dull T cell population was
observed. Thus, we considered that the CD4 molecules may be expressed on helper T
cells, but the CD4 expressing cells could not be detected with the three anti-pig
CD4 antibodies. Clinical abnormalities have not been observed in CD4.B pigs.
Significant differences were not observed in immunoglobulin concentrations
between CD4.A and CD4.B, though lower tendency was observed in plasma IgM
concentrations from CD4.B pigs >36-months-old. These results imply that the CD4.B
does not affect basic humoral immunity in vivo.
PMID- 26429413
TI - Local and systemic inflammatory and immunologic reactions to cyathostomin
larvicidal therapy in horses.
AB - Encysted cyathostomin larvae are ubiquitous in grazing horses. Arrested
development occurs in this population and can lead to an accumulation of encysted
larvae. Large numbers of tissue larvae place the horse at risk for developing
larval cyathostominosis. This disease complex is caused by mass emergence of
these larvae and is characterized by a generalized acute typhlocolitis and
manifests itself as a profuse protein-losing watery diarrhea with a reported case
fatality rate of about 50%. Two anthelmintic formulations have a label claim for
larvicidal therapy of these encysted stages; moxidectin and a five-day regimen of
fenbendazole. There is limited knowledge about inflammatory and immunologic
reactions to larvicidal therapy. This study was designed to evaluate blood acute
phase reactants as well as gene expression of pro-inflammatory cytokines, both
locally in the large intestinal walls and systemically. Further, mucosal tissue
samples were evaluated histopathologically as well as analyzed for gene
expression of pro- and anti-inflammatory cytokines, cluster of differentiation
(CD) cell surface proteins, and select transcription factors. Eighteen juvenile
horses with naturally acquired cyathostomin infections were randomly assigned to
three treatment groups; one group served as untreated controls (Group 1), one
received a five-day regimen of fenbendazole (10mg/kg) (Group 2), and one group
received moxidectin (0.4mg/kg) (Group 3). Horses were treated on day 0 and
euthanatized on days 18-20. Serum and whole blood samples were collected on days
0, 5, and 18. All horses underwent necropsy with collection of tissue samples
from the ventral colon and cecum. Acute phase reactants measured included serum
amyloid A, iron and fibrinogen, and the cytokines evaluated included interferon
gamma, tumor necrosis factor alpha, transforming growth factor (TGF)-beta, and
interleukins 1beta, 4, 5, 6, and 10. Transcription factors evaluated were FoxP3,
GATA3 and tBet, and CD markers included CD163, CD3z, CD4, CD40, and CD8b.
Histopathology revealed an inflammatory reaction with higher levels of
lymphocytes, T cells, B cells, eosinophils and fibrous tissue in the moxidectin
treated group compared to controls or horses treated with fenbendazole. No
apparent systemic reactions were observed. Expression of IL-5 and TGF-beta in
intestinal tissues was significantly lower in Group 3 compared to Group 1. This
study revealed a subtle inflammatory reaction to moxidectin, which is unlikely to
cause clinical issues.
PMID- 26429411
TI - The zebrafish galectins Drgal1-L2 and Drgal3-L1 bind in vitro to the infectious
hematopoietic necrosis virus (IHNV) glycoprotein and reduce viral adhesion to
fish epithelial cells.
AB - The infectious hematopoietic necrosis virus (IHNV; Rhabdoviridae,
Novirhabdovirus) infects teleost fish, such as salmon and trout, and is
responsible for significant losses in the aquaculture industry and in wild fish
populations. Although IHNV enters the host through the skin at the base of the
fins, the viral adhesion and entry mechanisms are not fully understood. In recent
years, evidence has accumulated in support of the key roles played by protein
carbohydrate interactions between host lectins secreted to the extracellular
space and virion envelope glycoproteins in modulating viral adhesion and
infectivity. In this study, we assessed in vitro the potential role(s) of
zebrafish (Danio rerio) proto type galectin-1 (Drgal1-L2) and a chimera galectin
3 (Drgal3-L1) in IHNV adhesion to epithelial cells. Our results suggest that the
extracellular Drgal1-L2 and Drgal3-L1 interact directly and in a carbohydrate
dependent manner with the IHNV glycosylated envelope and glycans on the
epithelial cell surface, significantly reducing viral adhesion.
PMID- 26429414
TI - The predictors of endoleaks after endovascular repair of experimentally produced
fusiform carotid aneurysm in canine.
AB - OBJECTIVE: Endoleaks constitute the main concern regarding the use of covered
stents in the treatment of intracranial aneurysms. We investigated immediate/late
endoleaks after stent-graft placement for the treatment of experimentally created
carotid fusiform aneurysm (FA) in a canine model. MATERIAL AND METHODS: Eighteen
carotid FAs in nine dogs receiving covered stents were followed. Their procedural
and angiographic data were collected immediately and six months after stenting.
Univariate analysis and multivariate logistic regression analysis were performed
to determine the factors predictive of immediate/late endoleaks. Receiver
operating characteristic curve analysis was performed to determine the best
cutoff values of the independent factors. RESULTS: All carotid FAs were
successfully treated with Willis covered stents and received a six-month follow
up. The rate of immediate and late endoleaks after stenting was 38.89% and
16.67%, respectively. Anchoring length was identified as independent predictor of
immediate endoleaks (P =0.037) and its best cutoff value was 3.06 mm (95%
confidence interval: 2.39-3.72). No parameters were identified to be independent
predictors of late endoleaks. CONCLUSIONS: Treating carotid FAs with Willis
covered stents is technically feasible. Most endoleaks heal spontaneously and
significantly correlate with anchoring length.
PMID- 26429415
TI - Feasibility of Using the Omaha System for Community-level Observations.
AB - OBJECTIVES: The purpose of this study was to determine the feasibility of using a
standardized language, the Omaha System, to capture community-level observations
to facilitate population assessment and electronic information exchange. The
objectives were: (1) to evaluate the feasibility of using the Omaha System at the
community level to reflect community observations and (2) to describe preliminary
results of community observations across international settings. DESIGN AND
SAMPLE: Descriptive. A dataset of 284 windshield surveys (community observations)
completed by nursing students in five countries: Mexico, New Zealand, Norway,
Turkey, and the United States. MEASURES: The Omaha System Problem Classification
Scheme provided standardized terms for assessment of communities in an online
checklist of 11 problems and their respective signs/symptoms. RESULTS:
Feasibility was demonstrated: students were able to describe community
observations using standardized terminology from the Omaha System. Preliminary
results describe variations in community signs and symptoms by location.
CONCLUSIONS: The Omaha System appears to be a useful tool for community-level
observations and a promising strategy for electronic exchange of population
health assessments.
PMID- 26429416
TI - Were Plasma Trace Element Levels Changed in the Children with ADHD?
PMID- 26429417
TI - Serum Zinc Concentration and C-Reactive Protein in Individuals with Human
Immunodeficiency Virus Infection: the Positive Living with HIV (POLH) Study.
AB - Low zinc levels and chronic inflammation are common in individuals infected with
human immunodeficiency virus (HIV). Zinc deficiency may promote systemic
inflammation, but research on the role of zinc in inflammation among HIV-positive
individuals taking account of anti-retroviral therapy is lacking. We assessed the
association between serum zinc and C-reactive protein (CRP) concentration in a
cohort of HIV-positive individuals. A cross-sectional survey was conducted among
311 HIV-positive individuals (177 men and 134 women) aged 18-60 years residing in
Kathmandu, Nepal. High-sensitive or regular serum CRP concentrations were
measured by the latex agglutination nephelometry or turbidimetric method, and
zinc concentrations were measured by the atomic absorption method. Relationships
were assessed using multiple linear regression analysis. The geometric means of
zinc in men and women were 73.83 and 71.93 ug/dL, respectively, and of CRP were
1.64 and 0.96 mg/L, respectively. Mean serum CRP concentration was significantly
decreased with increasing serum zinc concentration across zinc tertiles (P for
trend = 0.010), with mean serum CRP concentration in the highest tertile of serum
zinc concentration was 44.2 % lower than that in the lowest tertile. The mean
serum CRP concentrations in men and women in the highest tertile of serum zinc
concentrations were 30 and 35.9 % lower, respectively, than that in the lowest
tertile (P for trend = 0.263 and 0.162, respectively). We found a significant
inverse relation between log zinc and log CRP concentrations (beta for 1 unit
change in log zinc; beta = -1.79, p = 0.0003). Serum zinc concentration may be
inversely associated with serum CRP concentration in HIV-positive individuals.
PMID- 26429418
TI - Acute Kidney Injury in Children with Plasmodium falciparum Malaria: Determinants
for Mortality.
AB - ? BACKGROUND: Acute kidney injury (AKI) in P. falciparum malaria infection is an
important morbidity in children. The purpose of the present study was done to
observe the renal involvement, associated morbidities and outcome. ? METHODS: Out
of 156 patients with severe P. falciparum malaria, diagnosed on the basis of
compatible clinical presentations and positive malarial parasites in the
peripheral blood smear and/or histidine rich protein 2 antigen, 31 had AKI at
presentation and were analyzed. ? RESULTS: Of 31 (19.9%) patients with AKI, 4
were classified at risk, 11 injury, and 16 failure stage, as per pRIFLE criteria
(pediatric version of RIFLE [R = risk, I = injury, F = failure, L = loss E = end
stage kidney disease]). Mean age of children with AKI was 7.7 +/- 3.2 years. A
significantly higher proportion of patients with AKI had hypoglycemia (41.9%),
pulmonary edema (32.2%), and disseminated intravascular coagulation (DIC) (29.0%)
compared to those without AKI (18.4%, 4.8%, and 3.2%, respectively). Twelve
patients (38.7%) required peritoneal dialysis (PD), 8 (25.8%) died, and all were
in failure stage. The non-survivors had significantly higher blood urea (p =
0.005) and serum creatinine levels (p = 0.042), lower glomerular filtration rate
(p < 0.001), longer duration of illness (p = 0.003), and oliguria/anuria (p =
0.001) than survivors at admission. On logistic regression analysis, the
disseminated intravascular coagulation (DIC), jaundice and parasite density (>=
3+) were found to be significant factors contributing to mortality in children
with AKI. ? CONCLUSIONS: Acute kidney injury in falciparum malaria is one of the
severe systemic complications. Duration of illness and presence of comorbidities
adversely affected the outcome.
PMID- 26429419
TI - Patient Acceptability of the Yorkshire Dialysis Decision Aid (YoDDA) Booklet: A
Prospective Non-Randomized Comparison Study Across 6 Predialysis Services.
AB - ? BACKGROUND: Patients are satisfied with their kidney care but want more support
in making dialysis choices. Predialysis leaflets vary across services, with few
being sufficient to enable patients' informed decision making. We describe the
acceptability of a patient decision aid and feasibility of evaluating its
effectiveness within usual predialysis practice. ? METHODS: Prospective non
randomized comparison design, Usual Care or Usual Care Plus Yorkshire Dialysis
Decision Aid Booklet (+YoDDA), in 6 referral centers (Yorkshire-Humber, UK) for
patients with sustained deterioration of kidney function. Consenting (C) patients
completed questionnaires after predialysis consultation (T1), and 6 weeks later
(T2). Measures assessed YoDDA's utility to support patients' decisions and
integration within usual care. ? RESULTS: Usual Care (n = 105) and +YoDDA (n =
84) participant characteristics were similar: male (62%), white (94%), age (mean
= 62.6; standard deviation [SD] 14.4), kidney disease severity (glomerular
filtration rate [eGFR] mean = 14.7; SD 3.7); decisional conflict was < 25; choice
preference for home versus hospital dialysis approximately 50:50. Patients valued
receiving YoDDA, reading it on their own (96%), and sharing it with family (72%).
The +YoDDA participants had higher scores for understanding kidney disease,
reasoning about options, feeling in control, sharing their decision with family.
Study engagement varied by center (estimated range 14 - 49%; mean 45%);
participants varied in completion of decision quality measures. ? CONCLUSIONS:
Receiving YoDDA as part of predialysis education was valued and useful to
patients with worsening kidney disease. Integrating YoDDA actively within
predialysis programs will meet clinical guidelines and patient need to support
dialysis decision making in the context of patients' lifestyle.
PMID- 26429420
TI - Simultaneous Catheter Replacement for Infectious and Mechanical Complications
Without Interruption of Peritoneal Dialysis.
AB - ? BACKGROUND: Conventional management for peritoneal dialysis (PD)-related
infectious and mechanical complications that fails treatment includes catheter
removal and hemodialysis (HD) via a central venous catheter with the end result
that the majority of patients will not return to PD. Simultaneous catheter
replacement (SCR) can retain patients on PD by avoiding the scenario of staged
removal and reinsertion of catheters. The aim of this study was to evaluate a
protocol for SCR without interruption of PD. ? METHODS: Clinical outcomes were
analyzed for 55 consecutive SCRs performed from 2002 through 2012 and followed
through 2013. ? RESULTS: Simultaneous catheter replacements were performed for 28
cases of relapsing peritonitis, 12 cases of tunnel infection, and 15 cases of
mechanical catheter complications. All cases for peritonitis and tunnel infection
and 80% for mechanical complications continued PD on the day of surgery using a
low-volume, intermittent automated PD protocol. Systemic antibiotics were
continued for 2 weeks postoperatively (up to 4 weeks for Pseudomonas).
Simultaneous catheter replacement was performed as an outpatient procedure in
89.1% of cases. Only 1 of 55 procedures was complicated by peritonitis within 8
weeks. No catheter losses occurred during this postoperative timeframe. Long
term, SCR enabled a median technique survival of 5.1 years. ? CONCLUSIONS: In
most instances, SCR can be safely performed without interruption of PD for
selected cases of peritonitis and tunnel infection and for mechanical catheter
complications. The procedure spares the patient from a central venous catheter, a
shift to HD, the psychological ordeal of a change in dialysis modality, and a
second surgery to insert a new catheter.
PMID- 26429422
TI - Invited Article: A novel calibration method for the JET real-time far infrared
polarimeter and integration of polarimetry-based line-integrated density
measurements for machine protection of a fusion plant.
AB - In this paper, we present the work in the implementation of a new calibration for
the JET real-time polarimeter based on the complex amplitude ratio technique and
a new self-validation mechanism of data. This allowed easy integration of the
polarimetry measurements into the JET plasma density control (gas feedback
control) and as well as machine protection systems (neutral beam injection
heating safety interlocks). The new addition was used successfully during 2014
JET Campaign and is envisaged that will operate routinely from 2015 campaign
onwards in any plasma condition (including ITER relevant scenarios). This mode of
operation elevated the importance of the polarimetry as a diagnostic tool in the
view of future fusion experiments.
PMID- 26429423
TI - The spectral imaging facility: Setup characterization.
AB - The SPectral IMager (SPIM) facility is a laboratory visible infrared spectrometer
developed to support space borne observations of rocky bodies of the solar
system. Currently, this laboratory setup is used to support the DAWN mission,
which is in its journey towards the asteroid 1-Ceres, and to support the 2018 Exo
Mars mission in the spectral investigation of the Martian subsurface. The main
part of this setup is an imaging spectrometer that is a spare of the DAWN visible
infrared spectrometer. The spectrometer has been assembled and calibrated at
Selex ES and then installed in the facility developed at the INAF-IAPS laboratory
in Rome. The goal of SPIM is to collect data to build spectral libraries for the
interpretation of the space borne and in situ hyperspectral measurements of
planetary materials. Given its very high spatial resolution combined with the
imaging capability, this instrument can also help in the detailed study of
minerals and rocks. In this paper, the instrument setup is first described, and
then a series of test measurements, aimed to the characterization of the main
subsystems, are reported. In particular, laboratory tests have been performed
concerning (i) the radiation sources, (ii) the reference targets, and (iii)
linearity of detector response; the instrumental imaging artifacts have also been
investigated.
PMID- 26429421
TI - Longitudinal Trend in Lipid Profile of Incident Peritoneal Dialysis Patients is
Not Influenced by the Use of Biocompatible Solutions.
AB - ? BACKGROUND: The longitudinal trends of lipid parameters and the impact of
biocompatible peritoneal dialysis (PD) solutions on these levels remain to be
fully defined. The present study aimed to a) evaluate the influence of neutral
pH, low glucose degradation product (GDP) PD solutions on serum lipid parameters,
and b) explore the capacity of lipid parameters (total cholesterol [TC],
triglyceride [TG], high density lipoprotein [HDL], TC/HDL, low density
lipoprotein [LDL], very low density lipoprotein [VLDL]) to predict cardiovascular
events (CVE) and mortality in PD patients. ? METHODS: The study included 175
incident participants from the balANZ trial with at least 1 stored serum sample.
A composite CVE score was used as a primary clinical outcome measure. Multilevel
linear regression and Poisson regression models were fitted to describe the trend
of lipid parameters over time and its ability to predict composite CVE,
respectively. ? RESULTS: Small but statistically significant increases in serum
TG (coefficient 0.006, p < 0.001), TC/HDL (coefficient 0.004, p = 0.001), and
VLDL cholesterol (coefficient 0.005, p = 0.001) levels and a decrease in the
serum HDL cholesterol levels (coefficient -0.004, p = 0.009) were observed with
longer time on PD, whilst the type of PD solution (biocompatible vs standard)
received had no significant effect on these levels. Peritoneal dialysis glucose
exposure was significantly associated with trends in TG, TC/HDL, HDL and VLDL
levels. Baseline lipid parameter levels were not predictive of composite CVEs or
all-cause mortality. ? CONCLUSION: Serum TG, TC/HDL, and VLDL levels increased
and the serum HDL levels decreased with increasing PD duration. None of the lipid
parameters were significantly modified by biocompatible PD solution use over the
time period studied or predictive of composite CVE or mortality.
PMID- 26429424
TI - A polarized digital shearing speckle pattern interferometry system based on
temporal wavelet transformation.
AB - Digital shearing speckle pattern interferometry (DSSPI) has been recognized as a
practical tool in testing strain. The DSSPI system which is based on temporal
analysis is attractive because of its ability to measure strain dynamically. In
this paper, such a DSSPI system with Wollaston prism has been built. The
principles and system arrangement are described and the preliminary experimental
result of the displacement-derivative test of an aluminum plate is shown with the
wavelet transformation method and the Fourier transformation method. The
simulations have been conducted with the finite element method. The comparison of
the results shows that quantitative measurement of displacement-derivative has
been realized.
PMID- 26429425
TI - Development of ion beam figuring system with electrostatic deflection for
ultraprecise X-ray reflective optics.
AB - We developed an ion beam figuring system that utilizes electrostatic deflection.
The system can produce an arbitrary shape by deterministically scanning the ion
beam. The scan of the ion beam, which can be precisely controlled using only an
electrical signal, enables us to avoid degradation of the mirror shape caused by
imperfect acceleration or deceleration of a mechanically scanning stage.
Additionally, this surface figuring method can easily be combined with X-ray
metrology because the workpiece remains fixed during the figuring. We evaluated
the figuring accuracy of the system by fabricating a plano-elliptical mirror for
X-ray focusing. A mirror with a shape error of 1.4 nm root mean square (RMS) with
a maximum removal depth of 992 nm, which corresponds to figuring accuracy of
0.14% RMS, was achieved. After the second shape corrections, an elliptical shape
with a shape error of approximately 1 nm peak-to-valley, 0.48 nm RMS could be
fabricated. Then, the mirror surface was smoothed by a low-energy ion beam.
Consequently, a micro-roughness of 0.117 nm RMS, measured by atomic force
microscopy, was achieved over an area of 1 * 1 MUm(2).
PMID- 26429426
TI - Room-temperature calorimeter for x-ray free-electron lasers.
AB - We have developed a room-temperature calorimeter for absolute radiant power
measurements of x-ray free-electron lasers. This room-temperature calorimeter is
an electrical substitution device based on the equivalence of electrical and
radiant heating. Consequently, the measured radiant powers are traceable to
electrical standards, i.e., the International System Units (SI). We demonstrated
the performance of the room-temperature calorimeter by electrical power
measurements (offline tests). In the offline tests, the room-temperature
calorimeter was proven to be able to measure external powers up to at least 6.9
mW, which exceeds the upper limit (~4 mW) of a cryogenic radiometer (the primary
standard detector in Japan). In addition, measurement uncertainties of the room
temperature calorimeter were evaluated to be less than 1.0%, which is adequate
for the radiant power measurements of x-ray free-electron lasers. An indirect
comparison with the cryogenic radiometer was performed using a synchrotron
radiation source to confirm the validity of the absolute radiant powers measured
with the room-temperature calorimeter. The absolute radiant powers measured by
the calorimeter agreed with those measured by the cryogenic radiometer within
0.6%, which is less than the relative standard uncertainty of the comparison
(1.0%).
PMID- 26429427
TI - A closed-loop pump-driven wire-guided flow jet for ultrafast spectroscopy of
liquid samples.
AB - We describe the design and provide the results of the full characterization of a
closed-loop pump-driven wire-guided flow jet system. The jet has excellent
optical quality with a wide range of liquids spanning from alcohol to water based
solutions, including phosphate buffers used for biological samples. The thickness
of the jet film varies depending on the flow rate between 90 MUm and 370 MUm. The
liquid film is very stable, and its thickness varies only by 0.76% under optimal
conditions. Measured transmitted signal reveals a long term optical stability
(hours) with a RMS of 0.8%, less than the overall noise of the spectroscopy setup
used in our experiments. The closed loop nature of the overall jet design has
been optimized for the study of precious biological samples, in limited volumes,
to remove window contributions from spectroscopic observables. This feature is
particularly important for femtosecond studies in the UV range.
PMID- 26429428
TI - Demonstration of the high collection efficiency of a broadband Mo/Si multilayer
mirror with a graded multilayer coating on an ellipsoidal substrate.
AB - A graded and broadband Mo/Si multilayer mirror for EUV spectroscopy is
demonstrated. This mirror has an average reflectivity profile of 16% in the
wavelength region from 15 nm to 17 nm and an effective area of 1100-1500 mm(2).
This reflectivity is about 4 times larger than that of a standard Mo/Si
multilayer mirror on a 1 in. diameter substrate, showing that the mirror can be
used for measuring EUV fluorescence at wavelengths in the region around 15 nm to
17 nm.
PMID- 26429429
TI - Vapor phase tri-methyl-indium seeding system suitable for high temperature
spectroscopy and thermometry.
AB - Tri-methyl-indium (TMI) is used as an indium transport molecule to introduce
indium atoms to reactive hot gas flows/combustion environments for spectroscopic
diagnostics. A seeding system was constructed to allow the addition of an inert
TMI laden carrier gas into an air/fuel mixture burning consequently on a burner.
The amount of the seeded TMI in the carrier gas can be readily varied by
controlling the vapor pressure through the temperature of the container. The
seeding process was calibrated using the fluorescent emission intensity from the
indium 6(2)S1/2 -> 5(2)P1/2 and 6(2)S1/2 -> 5(2)P3/2 transitions as a function of
the calculated TMI seeding concentration over a range of 2-45 ppm. The response
was found to be linear over the range 3-22.5 ppm; at concentrations above 25 ppm
there is a loss of linearity attributable to self-absorption or loss of
saturation of TMI vapor pressure in the carrier gas flow. When TMI was introduced
into a post-combustion environment via an inert carrier gas, molecular transition
from InH and InOH radicals were observed in the flame emission spectrum. Combined
laser-induced fluorescence and absorption spectroscopy were applied to detect
indium atoms in the TMI seeded flame and the measured atomic indium concentration
was found to be at the ppm level. This method of seeding organometallic vapor
like TMI to a reactive gas flow demonstrates the feasibility for quantitative
spectroscopic investigations that may be applicable in various fields, e.g.,
chemical vapor deposition applications or temperature measurement in flames with
two-line atomic fluorescence.
PMID- 26429430
TI - Measurement of vacuum pressure with a magneto-optical trap: A pressure-rise
method.
AB - The lifetime of an atom trap is often limited by the presence of residual
background gases in the vacuum chamber. This leads to the lifetime being
inversely proportional to the pressure. Here, we use this dependence to estimate
the pressure and to obtain pressure rate-of-rise curves, which are commonly used
in vacuum science to evaluate the performance of a system. We observe different
rates of pressure increase in response to different levels of outgassing in our
system. Therefore, we suggest that this is a sensitive method which will find
useful applications in cold atom systems, in particular, where the inclusion of a
standard vacuum gauge is impractical.
PMID- 26429431
TI - A new compact soft x-ray spectrometer for resonant inelastic x-ray scattering
studies at PETRA III.
AB - We present a newly designed compact grating spectrometer for the energy range
from 210 eV to 1250 eV, which would include the Kalpha(1,2) emission lines of
vital elements like C, N, and O. The spectrometer is based on a grazing incidence
spherical varied line spacing grating with 2400 l/mm at its center and a radius
of curvature of 58 542 mm. First, results show a resolving power of around 1000
at an energy of 550 eV and a working spectrometer for high vacuum (10(-4) mbar)
environment without losing photon intensity.
PMID- 26429432
TI - Compton polarimeter for 10-30 keV x rays.
AB - We present a simple and versatile polarimeter for x rays in the energy range of
10-30 keV. It uses Compton scattering in low-Z materials such as beryllium or
boron carbide. The azimuthal distribution of the scattered x rays is sampled by
an array of 12 silicon PIN diodes operated at room temperature. We evaluated the
polarimetry performance using Monte-Carlo simulations and show experimental
results.
PMID- 26429433
TI - Dissemination stability and phase noise characteristics in a cascaded, fiber
based long-haul radio frequency dissemination network.
AB - To study the dissemination stability and phase noise characteristics of the
cascaded fiber-based RF dissemination, we perform an experiment using three sets
of RF modulated frequency dissemination systems. The experimental results show
that the total transfer stability of the cascaded system can be given by
sigma(T)(2)=?(i=1)(N)sigma(i)(2) (sigma(i) is the frequency dissemination
stability of the ith segment and N is the quantity of segments). Furthermore, for
each segment, the phase noise of recovered frequency signal is also measured. The
results show that for an N-segment, cascaded dissemination system, its stability
degrades only by a factor of N. This sub-linear relation makes the cascaded, RF
dissemination method a very attractive one for long-haul, time and frequency
dissemination network.
PMID- 26429434
TI - A hybrid electron cyclotron resonance metal ion source with integrated sputter
magnetron for the production of an intense Al+ ion beam.
AB - A metal ion source prototype has been developed: a combination of magnetron
sputter technology with 2.45 GHz electron cyclotron resonance (ECR) ion source
technology-a so called magnetron ECR ion source (MECRIS). An integrated ring
shaped sputter magnetron with an Al target is acting as a powerful metal atom
supply in order to produce an intense current of singly charged metal ions.
Preliminary experiments show that an Al(+) ion current with a density of 167
MUA/cm(2) is extracted from the source at an acceleration voltage of 27 kV.
Spatially resolved double Langmuir probe measurements and optical emission
spectroscopy were used to study the plasma states of the ion source: sputter
magnetron, ECR, and MECRIS plasma. Electron density and temperature as well as Al
atom density were determined as a function of microwave and sputter magnetron
power. The effect of ECR heating is strongly pronounced in the center of the
source. There the electron density is increased by one order of magnitude from 6
* 10(9) cm(-3) to 6 * 10(10) cm(-3) and the electron temperature is enhanced from
about 5 eV to 12 eV, when the ECR plasma is ignited to the magnetron plasma.
Operating the magnetron at constant power, it was observed that its discharge
current is raised from 1.8 A to 4.8 A, when the ECR discharge was superimposed
with a microwave power of 2 kW. At the same time, the discharge voltage decreased
from about 560 V to 210 V, clearly indicating a higher plasma density of the
MECRIS mode. The optical emission spectrum of the MECRIS plasma is dominated by
lines of excited Al atoms and shows a significant contribution of lines arising
from singly ionized Al. Plasma emission photography with a CCD camera was used to
prove probe measurements and to identify separated plasma emission zones
originating from the ECR and magnetron discharge.
PMID- 26429435
TI - Screens versus microarrays for ruggedized retarding potential analyzers.
AB - An array of highly miniaturized electrostatic lenses is shown to be a viable
replacement for meshes or screens in a retarding potential analyzer (RPA) where
mechanical ruggedness or the ability to intercept large currents of energetic
particles is desirable. Data from a prototype device are presented cross
calibrated with a traditional planar RPA indicating how the so-called microarray
configuration avoids energy-dependent transparency (either reduced or enhanced)
associated with meshes or screens while providing accurate energy analysis with
reasonable energy resolution. In contrast, another ruggedized configuration
employing a screen is presented, showing the severity of energy-dependent
enhanced transparency, verified by numerical simulation.
PMID- 26429436
TI - Beam based alignment and its relevance in Indus-2.
AB - Initially in the Indus-2 storage ring, the closed orbit distortion (COD) could be
best corrected to 1.3 mm rms in the horizontal and 0.43 mm rms in the vertical
plane. The strength of the corrector magnets required high values for COD
correction. This revealed that offsets in COD readout by the beam position
monitors (BPMs) played a role in not achieving a rms COD lower than the above
value. Thus, the offset between the electrical center of BPMs and the magnetic
center of the nearest quadrupole magnet could be estimated using the beam based
alignment (BBA) method. It prefers that the quadrupole magnet is able to be
controlled individually and active shunt power supply (ASPS) system was designed
for this purpose that works efficiently. This paper describes the methodology of
BBA, topology of ASPS and its performance, and COD minimization using the
measured BPM offsets. After BBA, the COD could be reduced to 0.45 mm rms and 0.2
mm rms in horizontal and vertical planes, respectively.
PMID- 26429437
TI - Commissioning of a frequency-resolved optical gating system at the OMEGA EP laser
facility: SpecFROG.
AB - We present the design and commissioning of a new single-shot, frequency-resolved
optical gating system on the OMEGA EP laser facility - dubbed "SpecFROG" - for
characterizing the instantaneous intensity and phase of ~10 ps pulses used to
study ultra-intense laser-plasma interactions. A polarization-gating geometry is
employed to ensure tha the diagnostic is broadband and has unambiguous time
directionality. SpecFROG is capable of characterizing ~10 s of mJ pulses with
durations between 0.5-25 ps with ?285 fs geometrical temporal blurring and ~0.1%
spectral shift resolutions over an adjustable total spectral shifting window of
~15% of the carrier wavelength lambdao; configurations currently exist for both
the fundamental (1omega, lambdao = 1.054 MUm) and second harmonic (2omega,
lambdao = 0.527 MUm) of the EP pulse. Initial specular reflectivity measurements
of the ~1 kJ, ~10 ps OMEGA EP laser off solid density aluminum targets suggest
drastically different scalings for specular pulse properties compared to
picosecond-scale pulses of comparable intensities.
PMID- 26429438
TI - Development of a stereo-symmetrical nanosecond pulsed power generator composed of
modularized avalanche transistor Marx circuits.
AB - Avalanche transistors have been widely studied and used in nanosecond high
voltage pulse generations. However, output power improvement is always limited by
the low thermal capacities of avalanche transistors, especially under high
repetitive working frequency. Parallel stacked transistors can effectively
improve the output current but the controlling of trigger and output synchronism
has always been a hard and complex work. In this paper, a novel stereo
symmetrical nanosecond pulsed power generator with high reliability was
developed. By analyzing and testing the special performances of the combined Marx
circuits, numbers of meaningful conclusions on the pulse amplitude, pulse back
edge, and output impedance were drawn. The combining synchronism of the generator
was confirmed excellent and lower conducting current through the transistors was
realized. Experimental results showed that, on a 50 Omega resistive load, pulses
with 1.5-5.2 kV amplitude and 5.3-14.0 ns width could be flexibly generated by
adjusting the number of combined modules, the supply voltage, and the module
type.
PMID- 26429439
TI - Two-dimensional wave-number spectral analysis techniques for phase contrast
imaging turbulence imaging data on large helical device.
AB - An analysis method for unfolding the spatially resolved wave-number spectrum and
phase velocity from the 2D CO2 laser phase contrast imaging system on the large
helical device is described. This is based on the magnetic shear technique which
identifies propagation direction from 2D spatial Fourier analysis of images
detected by a 6 * 8 detector array. Because the strongest modes have wave-number
at the lower end of the instrumental k range, high resolution spectral techniques
are necessary to clearly resolve the propagation direction and hence the spatial
distribution of fluctuations along the probing laser beam. Multiple-spatial point
cross-correlation averaging is applied before calculating the spatial power
spectrum. Different methods are compared, and it is found that the maximum
entropy method (MEM) gives best results. The possible generation of artifacts
from the over-narrowing of spectra are investigated and found not to be a
significant problem. The spatial resolution Deltarho (normalized radius) around
the peak wave-number, for conventional Fourier analysis, is ~0.5, making physical
interpretation difficult, while for MEM, Deltarho ~ 0.1.
PMID- 26429440
TI - The prototype imaging motional Stark effect diagnostic for ASDEX upgrade.
AB - This paper presents the development and testing of the prototype Imaging Motional
Stark-Effect (IMSE) diagnostic, designed for ASDEX upgrade. A detailed
description of the core hardware, theory of operation, and application to complex
MSE spectra are presented and analytical evaluation methods suitable for the
required accuracy are developed. The diagnostic is tested with a MSE-like
polarised spectrum to assess the accuracy of different modulation modes suggested
in previous works. Each is found to have small systematic errors due to non-ideal
effects of the components, which must be carefully examined. In particular, the
effect of intrinsic contrast that results from imperfect parallelism of the
birefringent plates is found to have a strong effect. Methods to mitigate and
correct for this are discussed. With the necessary corrections and calibrations,
the accuracy of polarisation orientation is shown to be within +/-0.2 degrees .
The effect of finite ellipticity is examined and the possibility to measure this
to an accuracy of +/-2.0 degrees is demonstrated. The system is shown to be
insensitive to broadband polarised background light, temperature variations, and
critically to variations in the details of the MSE spectrum.
PMID- 26429441
TI - Phillips-Tikhonov regularization with a priori information for neutron emission
tomographic reconstruction on Joint European Torus.
AB - A method of tomographic reconstruction of the neutron emissivity in the poloidal
cross section of the Joint European Torus (JET, Culham, UK) tokamak was
developed. Due to very limited data set (two projection angles, 19 lines of sight
only) provided by the neutron emission profile monitor (KN3 neutron camera), the
reconstruction is an ill-posed inverse problem. The aim of this work consists in
making a contribution to the development of reliable plasma tomography
reconstruction methods that could be routinely used at JET tokamak. The proposed
method is based on Phillips-Tikhonov regularization and incorporates a priori
knowledge of the shape of normalized neutron emissivity profile. For the purpose
of the optimal selection of the regularization parameters, the shape of
normalized neutron emissivity profile is approximated by the shape of normalized
electron density profile measured by LIDAR or high resolution Thomson scattering
JET diagnostics. In contrast with some previously developed methods of ill-posed
plasma tomography reconstruction problem, the developed algorithms do not include
any post-processing of the obtained solution and the physical constrains on the
solution are imposed during the regularization process. The accuracy of the
method is at first evaluated by several tests with synthetic data based on
various plasma neutron emissivity models (phantoms). Then, the method is applied
to the neutron emissivity reconstruction for JET D plasma discharge #85100. It is
demonstrated that this method shows good performance and reliability and it can
be routinely used for plasma neutron emissivity reconstruction on JET.
PMID- 26429442
TI - Blind source separation based x-ray image denoising from an image sequence.
AB - Blind source separation (BSS) based x-ray image denoising from an image sequence
is proposed. Without priori knowledge, the useful image signal can be separated
from an x-ray image sequence, for original images are supposed as different
combinations of stable image signal and random image noise. The BSS algorithms
such as fixed-point independent component analysis and second-order statistics
singular value decomposition are used and compared with multi-frame averaging
which is a common algorithm for improving image's signal-to-noise ratio (SNR).
Denoising performance is evaluated in SNR, standard deviation, entropy, and
runtime. Analysis indicates that BSS is applicable to image denoising; the
denoised image's quality will get better when more frames are included in an x
ray image sequence, but it will cost more time; there should be trade-off between
denoising performance and runtime, which means that the number of frames included
in an image sequence is enough.
PMID- 26429443
TI - A simple and non-contact optical imaging probe for evaluation of corneal
diseases.
AB - Non-contact imaging techniques are preferred in ophthalmology. Corneal disease is
one of the leading causes of blindness worldwide, and a possible way of detection
is by analyzing the shape and optical quality of the cornea. Here, a simple and
cost-effective, non-contact optical probe system is proposed and illustrated. The
probe possesses high spatial resolutions and is non-dependent on coupling medium,
which are significant for a clinician and patient friendly investigation. These
parameters are crucial, when considering an imaging system for the objective
diagnosis and management of corneal diseases. The imaging of the cornea is
performed on ex vivo porcine samples and subsequently on small laboratory
animals, in vivo. The clinical significance of the proposed study is validated by
performing imaging of the New Zealand white rabbit's cornea infected with
Pseudomonas.
PMID- 26429444
TI - Microwave soft x-ray microscopy for nanoscale magnetization dynamics in the 5-10
GHz frequency range.
AB - We present a scanning transmission x-ray microscopy setup combined with a novel
microwave synchronization scheme for studying high frequency magnetization
dynamics at synchrotron light sources. The sensitivity necessary to detect small
changes in the magnetization on short time scales and nanometer spatial
dimensions is achieved by combining the excitation mechanism with single photon
counting electronics that is locked to the synchrotron operation frequency. Our
instrument is capable of creating direct images of dynamical phenomena in the 5
10 GHz range, with high spatial resolution. When used together with circularly
polarized x-rays, the above capabilities can be combined to study magnetic
phenomena at microwave frequencies, such as ferromagnetic resonance (FMR) and
spin waves. We demonstrate the capabilities of our technique by presenting phase
resolved images of a ~6 GHz nanoscale spin wave generated by a spin torque
oscillator, as well as the uniform ferromagnetic precession with ~0.1 degrees
amplitude at ~9 GHz in a micrometer-sized cobalt strip.
PMID- 26429445
TI - Scanning nonlinear dielectric potentiometry.
AB - Measuring spontaneous polarization and permanent dipoles on surfaces and
interfaces on the nanoscale is difficult because the induced electrostatic fields
and potentials are often influenced by other phenomena such as the existence of
monopole fixed charges, screening charges, and contact potential differences. A
method based on tip-sample capacitance detection and bias feedback is proposed
which is only sensitive to polarization- or dipole-induced potentials, unlike
Kelvin probe force microscopy. The feasibility of this method was demonstrated by
simultaneously measuring topography and polarization-induced potentials on a
reconstructed Si(111)-(7 * 7) surface with atomic resolution.
PMID- 26429446
TI - Simultaneous differential spinning disk fluorescence optical sectioning
microscopy and nanomechanical mapping atomic force microscopy.
AB - Combined microscopy techniques offer the life science research community a
powerful tool to investigate complex biological systems and their interactions.
Here, we present a new combined microscopy platform based on fluorescence optical
sectioning microscopy through aperture correlation microscopy with a Differential
Spinning Disk (DSD) and nanomechanical mapping with an Atomic Force Microscope
(AFM). The illumination scheme of the DSD microscope unit, contrary to standard
single or multi-point confocal microscopes, provides a time-independent
illumination of the AFM cantilever. This enables a distortion-free simultaneous
operation of fluorescence optical sectioning microscopy and atomic force
microscopy with standard probes. In this context, we discuss sample heating due
to AFM cantilever illumination with fluorescence excitation light. Integration of
a DSD fluorescence optical sectioning unit with an AFM platform requires
mitigation of mechanical noise transfer of the spinning disk. We identify and
present two solutions to almost annul this noise in the AFM measurement process.
The new combined microscopy platform is applied to the characterization of a
DOPC/DOPS (4:1) lipid structures labelled with a lipophilic cationic
indocarbocyanine dye deposited on a mica substrate.
PMID- 26429447
TI - Neutron, fluorescence, and optical imaging: An in situ combination of
complementary techniques.
AB - An apparatus which enables the simultaneous combination of three complementary
imaging techniques, optical imaging, fluorescence imaging, and neutron
radiography, is presented. While each individual technique can provide
information on certain aspects of the sample and their time evolution, a
combination of the three techniques in one setup provides a more complete and
consistent data set. The setup can be used in transmission and reflection modes
and thus with optically transparent as well as opaque samples. Its capabilities
are illustrated with two examples. A polymer hydrogel represents a transparent
sample and the diffusion of fluorescent particles into and through this polymer
matrix is followed. In reflection mode, the absorption of solvent by a nile red
functionalized mesoporous silica powder and the corresponding change in
fluorescent signal are studied.
PMID- 26429448
TI - Compact low temperature scanning tunneling microscope with in-situ sample
preparation capability.
AB - We report on the design of a compact low temperature scanning tunneling
microscope (STM) having in-situ sample preparation capability. The in-situ sample
preparation chamber was designed to be compact allowing quick transfer of samples
to the STM stage, which is ideal for preparing temperature sensitive samples such
as ultra-thin metal films on semiconductor substrates. Conventional spring
suspensions on the STM head often cause mechanical issues. To address this
problem, we developed a simple vibration damper consisting of welded metal
bellows and rubber pads. In addition, we developed a novel technique to ensure an
ultra-high-vacuum (UHV) seal between the copper and stainless steel, which
provides excellent reliability for cryostats operating in UHV. The performance of
the STM was tested from 2 K to 77 K by using epitaxial thin Pb films on Si. Very
high mechanical stability was achieved with clear atomic resolution even when
using cryostats operating at 77 K. At 2 K, a clean superconducting gap was
observed, and the spectrum was easily fit using the BCS density of states with
negligible broadening.
PMID- 26429449
TI - Dynamic tunneling force microscopy for characterizing electronic trap states in
non-conductive surfaces.
AB - Dynamic tunneling force microscopy (DTFM) is a scanning probe technique for real
space mapping and characterization of individual electronic trap states in non
conductive films with atomic scale spatial resolution. The method is based upon
the quantum mechanical tunneling of a single electron back and forth between a
metallic atomic force microscopy tip and individual trap states in completely non
conducting surface. This single electron shuttling is measured by detecting the
electrostatic force induced on the probe tip at the shuttling frequency. In this
paper, the physical basis for the DTFM method is unfolded through a physical
model and a derivation of the dynamic tunneling signal as a function of several
experimental parameters is shown. Experimental data are compared with the
theoretical simulations, showing quantitative consistency and verifying the
physical model used. The experimental system is described and representative
imaging results are shown.
PMID- 26429450
TI - A widefield fluorescence microscope with a linear image sensor for image
cytometry of biospecimens: Considerations for image quality optimization.
AB - Linear image sensors have been widely used in numerous research and industry
applications to provide continuous imaging of moving objects. Here, we present a
widefield fluorescence microscope with a linear image sensor used to image
translating objects for image cytometry. First, a calibration curve was
characterized for a custom microfluidic chamber over a span of volumetric pump
rates. Image data were also acquired using 15 MUm fluorescent polystyrene spheres
on a slide with a motorized translation stage in order to match linear
translation speed with line exposure periods to preserve the image aspect ratio.
Aspect ratios were then calculated after imaging to ensure quality control of
image data. Fluorescent beads were imaged in suspension flowing through the
microfluidics chamber being pumped by a mechanical syringe pump at 16 MUl min(-1)
with a line exposure period of 150 MUs. The line period was selected to acquire
images of fluorescent beads with a 40 dB signal-to-background ratio. A motorized
translation stage was then used to transport conventional glass slides of stained
cellular biospecimens. Whole blood collected from healthy volunteers was stained
with 0.02% (w/v) proflavine hemisulfate was imaged to highlight leukocyte
morphology with a 1.56 mm * 1.28 mm field of view (1540 ms total acquisition
time). Oral squamous cells were also collected from healthy volunteers and
stained with 0.01% (w/v) proflavine hemisulfate to demonstrate quantifiable
subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n =
75), with a resolution of 0.31 MUm pixels(-1).
PMID- 26429451
TI - Sub-Kelvin magnetic and electrical measurements in a diamond anvil cell with in
situ tunability.
AB - We discuss techniques for performing continuous measurements across a wide range
of pressure-field-temperature phase space, combining the milli-Kelvin
temperatures of a helium dilution refrigerator with the giga-Pascal pressures of
a diamond anvil cell and the Tesla magnetic fields of a superconducting magnet.
With a view towards minimizing remnant magnetic fields and background magnetic
susceptibility, we characterize high-strength superalloy materials for the
pressure cell assembly, which allows high fidelity measurements of low-field
phenomena such as superconductivity below 100 mK at pressures above 10 GPa. In
situ tunability and measurement of the pressure permit experiments over a wide
range of pressure, while at the same time making possible precise steps across
abrupt phase transitions such as those from insulator to metal.
PMID- 26429452
TI - A rotational and axial motion system load frame insert for in situ high energy x
ray studies.
AB - High energy x-ray characterization methods hold great potential for gaining
insight into the behavior of materials and providing comparison datasets for the
validation and development of mesoscale modeling tools. A suite of techniques
have been developed by the x-ray community for characterizing the 3D structure
and micromechanical state of polycrystalline materials; however, combining these
techniques with in situ mechanical testing under well characterized and
controlled boundary conditions has been challenging due to experimental design
requirements, which demand new high-precision hardware as well as access to high
energy x-ray beamlines. We describe the design and performance of a load frame
insert with a rotational and axial motion system that has been developed to meet
these requirements. An example dataset from a deforming titanium alloy
demonstrates the new capability.
PMID- 26429453
TI - Compact AC susceptometer for fast sample characterization down to 0.1 K.
AB - We report a new design of an AC magnetic susceptometer compatible with the
Physical Properties Measurement System (PPMS) by Quantum Design, as well as with
its adiabatic demagnetization refrigerator option. With the elaborate compact
design, the susceptometer allows simple and quick sample mounting process. The
high performance of the susceptometer down to 0.1 K is demonstrated using several
superconducting and magnetic materials. This susceptometer provides a method to
quickly investigate qualities of a large number of samples in the wide
temperature range between 0.1 and 300 K.
PMID- 26429454
TI - Producing and imaging a thin line of He*2 molecular tracers in helium-4.
AB - Cryogenic helium-4 has long been recognized as a useful material in fluids
research. The unique properties of helium-4 in the gaseous phase and the normal
liquid phase allow for the generation of turbulent flows with exceptionally high
Reynolds and Rayleigh numbers. In the superfluid phase, helium-4 exhibits two
fluid hydrodynamics and possesses fascinating properties due to its quantum
nature. However, studying the flows in helium-4 has been very challenging largely
due to the lack of effective visualization and velocimetry techniques. In this
article, we discuss the development of novel instrumentation for flow
visualization in helium based on the generation and imaging of thin lines of
metastable He*2 tracer molecules. These molecular tracers are created via
femtosecond-laser field-ionization of helium atoms and can be imaged using a
laser-induced fluorescence technique. By observing the displacement and
distortion of the tracer lines in helium, quantitative information about the flow
field can be extracted. We present experimental results in the study of thermal
counterflow in superfluid helium that validate the concept of this technique. We
also discuss anticipated future developments of this powerful visualization
technique.
PMID- 26429455
TI - Quick scanning monochromator for millisecond in situ and in operando X-ray
absorption spectroscopy.
AB - The design and capabilities of a novel Quick scanning Extended X-ray Absorption
Fine Structure (QEXAFS) monochromator are presented. The oscillatory movement of
the crystal stage is realized by means of a unique open-loop driving scheme
operating a direct drive torque motor. The entire drive mechanics are installed
inside of a goniometer located on the atmospheric side of the vacuum chamber.
This design allows remote adjustment of the oscillation frequency and spectral
range, giving complete control of QEXAFS measurements. It also features a real
step-scanning mode, which operates without a control loop to prevent induced
vibrations. Equipped with Si(111) and Si(311) crystals on a single stage, it
facilitates an energy range from 4.0 keV to 43 keV. Extended X-ray absorption
fine structure spectra up to k = 14.4 A(-1) have been acquired within 17 ms and X
ray absorption near edge structure spectra covering more than 200 eV within 10
ms. The achieved data quality is excellent as shown by the presented
measurements.
PMID- 26429456
TI - Aerodynamic levitator for large-sized glassy material production.
AB - Containerless aerodynamic levitation processing is a unique technology for the
fabrication of bulk non-crystalline materials. Using conventional aerodynamic
levitation, a high reflective index (RI) material (BaTi2O5 and LaO3/2-TiO2-ZrO2
system) was developed with a RI greater than approximately 2.2, which is similar
to that of diamond. However, the glass size was small, approximately 3 mm in
diameter. Therefore, it is essential to produce large sized materials for future
optical materials applications, such as camera lenses. In this study, a new
aerodynamic levitator was designed to produce non-crystalline materials with
diameters larger than 6 mm. The concept of this new levitator was to set up a
reduced pressure at the top of the molten samples without generating turbulent
flow. A numerical simulation was also performed to verify the concept.
PMID- 26429457
TI - Image analysis of speckle patterns as a probe of melting transitions in laser
heated diamond anvil cell experiments.
AB - The precision of melting curve measurements using laser-heated diamond anvil cell
(LHDAC) is largely limited by the correct and reliable determination of the onset
of melting. We present a novel image analysis of speckle interference patterns in
the LHDAC as a way to define quantitative measures which enable an objective
determination of the melting transition. Combined with our low-temperature
customized IR pyrometer, designed for measurements down to 500 K, our setup
allows studying the melting curve of materials with low melting temperatures,
with relatively high precision. As an application, the melting curve of Te was
measured up to 35 GPa. The results are found to be in good agreement with
previous data obtained at pressures up to 10 GPa.
PMID- 26429458
TI - Tandem ion mobility spectrometry coupled to laser excitation.
AB - This manuscript describes a new experimental setup that allows to perform tandem
ion mobility spectrometry (IMS) measurements and which is coupled to a high
resolution time-of-flight mass spectrometer. It consists of two 79 cm long drift
tubes connected by a dual ion funnel assembly. The setup was built to permit
laser irradiation of the ions in the transfer region between the two drift tubes.
This geometry allows selecting ions according to their ion mobility in the first
drift tube, to irradiate selected ions, and examine the ion mobility of the
product ions in the second drift tube. Activation by collision is possible in the
same region (between the two tubes) and between the second tube and the time-of
flight. IMS-IMS experiments on Ubiquitin are reported. We selected a given isomer
of charge state +7 and explored its structural rearrangement following
collisional activation between the two drift tubes. An example of IMS-laser-IMS
experiment is reported on eosin Y, where laser irradiation was used to produce
radical ions by electron photodetachment starting from doubly deprotonated
species. This allowed measuring the collision cross section of the radical photo
product, which cannot be directly produced with an electrospray source.
PMID- 26429459
TI - An adaptable multiple power source for mass spectrometry and other scientific
instruments.
AB - An Adaptable Multiple Power Source (AMPS) system has been designed and
constructed. The AMPS system can provide up to 16 direct current (DC) (+/-400 V;
5 mA), 4 radio frequency (RF) (two 500 VPP sinusoidal signals each, 0.5-5 MHz)
channels, 2 high voltage sources (+/-6 kV), and one ~40 W, 250 degrees C
temperature-regulated heater. The system is controlled by a microcontroller,
capable of communicating with its front panel or a computer. It can assign not
only pre-saved fixed DC and RF signals but also profiled DC voltages. The AMPS
system is capable of driving many mass spectrometry components and ancillary
devices and can be adapted to other instrumentation/engineering projects.
PMID- 26429460
TI - Influence of temperature on period of torsion pendulum with a high-Q fused silica
fiber.
AB - Due to the high-Q fused silica fiber's extreme sensitivity to temperature change,
the period estimation of torsion pendulum with high precision depends on the
effective correction of the thermoelastic effect. In the measurement of G with
the time-of-swing method, we analyze the complex relation between temperature and
the pendulum's period and propose a developed method to find the shear
thermoelasticity coefficient as well as isolate the influence of temperature on
period alone. The result shows that the shear thermoelasticity coefficient is
101(2) * 10(-6)/ degrees C, the resultant correction to Delta(omega(2)) is
9.16(0.18) ppm, and the relative uncertainty to G is less than 1 ppm.
PMID- 26429461
TI - Conducted noise analysis and protection of 45 kJ/s, +/-50 kV capacitor charging
power supply when interfaced with repetitive Marx based pulse power system.
AB - Pulse power systems with highly dynamic loads like klystron, backward wave
oscillator (BWO), and magnetron generate highly dynamic noise. This noise leads
to frequent failure of controlled switches in the inverter stage of charging
power supply. Designing a reliable and compatible power supply for pulse power
applications is always a tricky job when charging rate is in multiples of 10
kJ/s. A +/-50 kV and 45 kJ/s capacitor charging power supply based on 4th order
LCLC resonant topology has been developed for a 10 Hz repetitive Marx based
system. Conditions for load independent constant current and zero current
switching (ZCS) are derived mathematically. Noise generated at load end due to
dynamic load is tackled effectively and reduction in magnitude noise voltage is
achieved by providing shielding between primary and secondary of high voltage
high frequency transformer and with LCLC low pass filter. Shielding scales down
the ratio between coupling capacitance (Cc) and the collector-emitter capacitance
of insulated gate bi-polar transistor switch, which in turn reduces the common
mode noise voltage magnitude. The proposed 4th order LCLC resonant network acts
as a low pass filter for differential mode noise in the reverse direction (from
load to source). Power supply has been tested repeatedly with 5 Hz repetition
rate with repetitive Marx based system connected with BWO load working fine
without failure of single switch in the inverter stage.
PMID- 26429462
TI - A time domain based method for the accurate measurement of Q-factor and resonance
frequency of microwave resonators.
AB - We present a novel method to determine the resonant frequency and quality factor
of microwave resonators which is faster, more stable, and conceptually simpler
than the yet existing techniques. The microwave resonator is pumped with the
microwave radiation at a frequency away from its resonance. It then emits an
exponentially decaying radiation at its eigen-frequency when the excitation is
rapidly switched off. The emitted microwave signal is down-converted with a
microwave mixer, digitized, and its Fourier transformation (FT) directly yields
the resonance curve in a single shot. Being a FT based method, this technique
possesses the Fellgett (multiplex) and Connes (accuracy) advantages and it
conceptually mimics that of pulsed nuclear magnetic resonance. We also establish
a novel benchmark to compare accuracy of the different approaches of microwave
resonator measurements. This shows that the present method has similar accuracy
to the existing ones, which are based on sweeping or modulating the frequency of
the microwave radiation.
PMID- 26429463
TI - Impact of laser phase and amplitude noises on streak camera temporal resolution.
AB - Streak cameras are now reaching sub-picosecond temporal resolution. In cumulative
acquisition mode, this resolution does not entirely rely on the electronic or the
vacuum tube performances but also on the light source characteristics. The light
source, usually an actively mode-locked laser, is affected by phase and amplitude
noises. In this paper, the theoretical effects of such noises on the
synchronization of the streak system are studied in synchroscan and triggered
modes. More precisely, the contribution of band-pass filters, delays, and time
walk is ascertained. Methods to compute the resulting synchronization jitter are
depicted. The results are verified by measurement with a streak camera combined
with a Ti:Al2O3 solid state laser oscillator and also a fiber oscillator.
PMID- 26429464
TI - A magneto-optical microscope for quantitative measurement of magnetic
microstructures.
AB - An optical system is presented to quantitatively map the stray magnetic fields of
microscale magnetic structures, with field resolution down to 50 MUT and spatial
resolution down to 4 MUm. The system uses a magneto-optical indicator film (MOIF)
in conjunction with an upright reflective polarizing light microscope to generate
optical images of the magnetic field perpendicular to the image plane. A novel
single light path construction and discrete multi-image polarimetry processing
method are used to extract quantitative areal field measurements from the optical
images. The integrated system including the equipment, image analysis software,
and experimental methods are described. MOIFs with three different magnetic field
ranges are calibrated, and the entire system is validated by measurement of the
field patterns from two calibration samples.
PMID- 26429465
TI - Low-noise and high-speed photodetection system using optical feedback with a
current amplification function.
AB - A photodetection system with an optical-feedback circuit accompanied by current
amplification was fabricated to minimize the drawbacks associated with a
transimpedance amplifier (TIA) with a very high resistance feedback resistor.
Current amplification was implemented by extracting an output light from the same
light source that emitted the feedback light. The current gain corresponds to the
ratio of the photocurrent created by the output light to that created by the
feedback light because the feedback current value is identical to the input
photocurrent value generated by an input light to be measured. The current gain
has no theoretical limit. The output light was detected by a photodiode with a
TIA having a small feedback resistance. The expression for the input-referred
noise current of the optical-feedback photodetection system was derived, and the
trade-off between sensitivity and response, which is a characteristic of TIA, was
found to considerably improve. An optical-feedback photodetection system with an
InGaAs pin photodiode was fabricated. The measured noise equivalent power of the
system was 1.7 fW/Hz(1/2) at 10 Hz and 1.3 MUm, which is consistent with the
derived expression. The time response of the system was found to deteriorate with
decreasing photocurrent. The 50% rise time for a light pulse input increased from
3.1 MUs at a photocurrent of 10 nA to 15 MUs at photocurrents below 10 pA. The
bandwidth of the input-referred noise current was 7 kHz, which is consistent with
rise times below 10 pA.
PMID- 26429466
TI - A compact, high-voltage pulsed charging system based on an air-core pulse
transformer.
AB - Charging systems of pulsed power generators on mobile platforms are expected to
be compact and provide high pulsed power, high voltage output, and high
repetition rate. In this paper, a high-voltage pulsed charging system with the
aforementioned characteristics is introduced, which can be applied to charge a
high-voltage load capacitor. The operating principle of the system and the
technical details of the components in the system are described in this paper.
The experimental results show that a 600 nF load capacitor can be charged to 60
kV at 10 Hz by the high-voltage pulsed charging system for a burst of 0.5 s. The
weight and volume of the system are 60 kg and 600 * 500 * 380 mm(3),
respectively.
PMID- 26429467
TI - Simple-design ultra-low phase noise microwave frequency synthesizers for high
performing Cs and Rb vapor-cell atomic clocks.
AB - We report on the development and characterization of novel 4.596 GHz and 6.834
GHz microwave frequency synthesizers devoted to be used as local oscillators in
high-performance Cs and Rb vapor-cell atomic clocks. The key element of the
synthesizers is a custom module that integrates a high spectral purity 100 MHz
oven controlled quartz crystal oscillator frequency-multiplied to 1.6 GHz with
minor excess noise. Frequency multiplication, division, and mixing stages are
then implemented to generate the exact output atomic resonance frequencies.
Absolute phase noise performances of the output 4.596 GHz signal are measured to
be -109 and -141 dB rad(2)/Hz at 100 Hz and 10 kHz Fourier frequencies,
respectively. The phase noise of the 6.834 GHz signal is -105 and -138 dB
rad(2)/Hz at 100 Hz and 10 kHz offset frequencies, respectively. The performances
of the synthesis chains contribute to the atomic clock short term fractional
frequency stability at a level of 3.1 * 10(-14) for the Cs cell clock and 2 * 10(
14) for the Rb clock at 1 s averaging time. This value is comparable with the
clock shot noise limit. We describe the residual phase noise measurements of key
components and stages to identify the main limitations of the synthesis chains.
The residual frequency stability of synthesis chains is measured to be at the 10(
15) level for 1 s integration time. Relevant advantages of the synthesis design,
using only commercially available components, are to combine excellent phase
noise performances, simple-architecture, low-cost, and to be easily customized
for signal output generation at 4.596 GHz or 6.834 GHz for applications to Cs or
Rb vapor-cell frequency standards.
PMID- 26429468
TI - New methodology for the thermal characterization of thermoelectric liquids.
AB - A new and accurate method for the thermal characterization of thermoelectric
liquids is proposed. The experiment is based on a self-generated voltage due to
the Seebeck effect. This voltage is provided by the sample when one of its two
faces is thermally excited using a modulated laser. The sample used is
tetradodecylammonium nitrate salt/1-octanol mixture, with high Seebeck
coefficient. The thermal properties of the used sample (thermal diffusivity,
effusivity, and conductivity) are found and compared to those obtained by other
photothermal techniques. In addition to this, a study of the electrolyte thermal
parameters with the variation of tetradodecylammonium nitrate concentration was
also carried out. This new method is promising due to its accuracy and its
simplicity.
PMID- 26429469
TI - A novel voice coil motor-driven compliant micropositioning stage based on flexure
mechanism.
AB - This paper presents a 2-degrees of freedom flexure-based micropositioning stage
with a flexible decoupling mechanism. The stage is composed of an upper planar
stage and four vertical support links to improve the out-of-plane stiffness. The
moving platform is driven by two voice coil motors, and thus it has the
capability of large working stroke. The upper stage is connected with the base
through six double parallel four-bar linkages mechanisms, which are orthogonally
arranged to implement the motion decoupling in the x and y directions. The
vertical support links with serially connected hook joints are utilized to
guarantee good planar motion with heavy-loads. The static stiffness and the
dynamic resonant frequencies are obtained based on the theoretical analyses.
Finite element analysis is used to investigate the characteristics of the
developed stage. Experiments are carried out to validate the established models
and the performance of the developed stage. It is noted that the developed stage
has the capability of translational motion stroke of 1.8 mm and 1.78 mm in
working axes. The maximum coupling errors in the x and y directions are 0.65% and
0.82%, respectively, and the motion resolution is less than 200 nm. The
experimental results show that the developed stage has good capability for
trajectory tracking.
PMID- 26429470
TI - Influence of cavity loss on an extrinsic Fabry-Perot cavity intensity-based
pressure sensor.
AB - We present an extrinsic Fabry-Perot cavity intensity-based pressure sensor that
mainly comprises a single-mode fiber end and an elastic monocrystalline silicon
layer bonded to a silicon diaphragm. We investigated the influence of cavity loss
on the performance indexes (PIS) of the intensity-based extrinsic Fabry-Perot
cavity optical fiber pressure sensor. A buffer unit made of three incompressible
oil cavities attenuated outside pressure and transformed pressure information
into cavity length microchange information. Experimental results indicated that,
under center quadrature-points within the linear regions of adjacent fringes, for
an applied 40 kPa external pressure, cavity length was modulated by pressures of
69.9 kPa-109.9 kPa, 150.1 kPa-190 kPa, 220.1 kPa-259.9 kPa, and 279.9 kPa-319.9
kPa, output intensity ranges increased as 1 MUW, 1.02 MUW, 1.03 MUW, and 1.05
MUW, sensitivity increased as 0.01909 MUW/kPa, 0.01986 MUW/kPa, 0.02127 MUW/kPa,
and 0.02387 MUW/kPa, but linearity degraded, as indicated by the standard
deviation of linear fits of 0.02607, 0.02664, 0.02935, and 0.04879 due to cavity
loss. Furthermore, the pressure ranges within the same quarter period decreased
as 40 kPa, 37.45 kPa, 32.4 kPa, and 30.15 kPa. Consequently, the same lengths of
linear regions within adjacent fringes of an approximately sinusoidal curve
corresponded to different measurement ranges, linearities, and sensitivities.
Initial cavity length must be chosen to optimize both signal strength and the PIS
studied here in manufacturing this type sensor.
PMID- 26429472
TI - A novel full-angle scanning light scattering profiler to quantitatively evaluate
forward and backward light scattering from intraocular lenses.
AB - Glare, glistenings, optical defects, dysphotopsia, and poor image quality are a
few of the known deficiencies of intraocular lenses (IOLs). All of these optical
phenomena are related to light scatter. However, the specific direction that
light scatters makes a critical difference between debilitating glare and a
slightly noticeable decrease in image quality. Consequently, quantifying the
magnitude and direction of scattered light is essential to appropriately evaluate
the safety and efficacy of IOLs. In this study, we introduce a full-angle
scanning light scattering profiler (SLSP) as a novel approach capable of
quantitatively evaluating the light scattering from IOLs with a nearly 360
degrees view. The SLSP method can simulate in situ conditions by controlling the
parameters of the light source including angle of incidence. This testing
strategy will provide a more effective nonclinical approach for the evaluation of
IOL light scatter.
PMID- 26429471
TI - A fully integrated standalone portable cavity ringdown breath acetone analyzer.
AB - Breath analysis is a promising new technique for nonintrusive disease diagnosis
and metabolic status monitoring. One challenging issue in using a breath
biomarker for potential particular disease screening is to find a quantitative
relationship between the concentration of the breath biomarker and clinical
diagnostic parameters of the specific disease. In order to address this issue, we
need a new instrument that is capable of conducting real-time, online breath
analysis with high data throughput, so that a large scale of clinical test (more
subjects) can be achieved in a short period of time. In this work, we report a
fully integrated, standalone, portable analyzer based on the cavity ringdown
spectroscopy technique for near-real time, online breath acetone measurements.
The performance of the portable analyzer in measurements of breath acetone was
interrogated and validated by using the certificated gas chromatography-mass
spectrometry. The results show that this new analyzer is useful for reliable
online (online introduction of a breath sample without pre-treatment) breath
acetone analysis with high sensitivity (57 ppb) and high data throughput (one
data per second). Subsequently, the validated breath analyzer was employed for
acetone measurements in 119 human subjects under various situations. The
instrument design, packaging, specifications, and future improvements were also
described. From an optical ringdown cavity operated by the lab-set electronics
reported previously to this fully integrated standalone new instrument, we have
enabled a new scientific tool suited for large scales of breath acetone analysis
and created an instrument platform that can even be adopted for study of other
breath biomarkers by using different lasers and ringdown mirrors covering
corresponding spectral fingerprints.
PMID- 26429473
TI - Broadband high-sensitivity current-sensing device utilizing nonlinear
magnetoelectric medium and nanocrystalline flux concentrator.
AB - A broadband current-sensing device with frequency-conversion mechanism consisting
of Terfenol-D/Pb(Zr.Ti)O3 (PZT)/Terfenol-D magnetoelectric laminate and
Fe73.5Cu1Nb3Si13.5B9 nanocrystalline flux concentrator is fabricated and
characterized. For the purpose of acquiring resonance-enhanced sensitivity within
broad bandwidth, a frequency-modulation mechanism is introduced into the
presented device through the nonlinearity of field-dependence giant
magnetostrictive materials. The presented configuration provides a solution to
monitor the weak currents and achieves resonance-enhanced sensitivity of 178.4
mV/A at power-line frequency, which exhibits ~3.86 times higher than that of
direct output at power-line frequency of 50 Hz. Experimental results demonstrate
that a weak step-change input current of 1 mA can be clearly distinguished by the
output amplitude or phase. This miniature current-sensing device provides a
promising application in power-line weak current measurement.
PMID- 26429474
TI - A dynamic pressure view cell for acoustic stimulation of fluids--Micro-bubble
generation and fluid movement in porous media.
AB - The development and baseline operation of an acoustic view cell for observing
fluids, and fluid-fluid and fluid-solid interfaces in porous media over the
frequency range of 10-5000 Hz is described. This range includes the industrially
relevant frequency range 500-5000 Hz that is not covered by existing devices.
Pressure waveforms of arbitrary shape are generated in a 17.46 mm ID by 200 mm
and 690.5 mm long glass tubes at flow rates up to 200 ml/min using a syringe
pump. Peak-to-peak amplitudes exceeding 80 kPa are readily realized at
frequencies from 10 to 5000 Hz in bubble free fluids when actuated with 20 Vpp as
exemplified using castor oil. At resonant frequencies, peak-to-peak pressure
amplitudes exceeding 500 kPa were obtained (castor oil at 2100 Hz when actuated
with 20 Vpp). Impacts of vibration on macroscopic liquid-liquid and liquid-vapour
interfaces and interface movement are illustrated. Pressure wave transmission and
attenuation in a fluid saturated porous medium, randomly packed 250-330 MUm
spherical silica beads, is also demonstrated. Attenuation differences and
frequency shifts in resonant peaks are used to detect the presence and generation
of dispersed micro-bubbles (<180 MUm diameter), and bubbles within porous media
that are not readily visualized. Envisioned applications include assessment of
the impacts of vibration on reaction, mass transfer, and flow/flow pattern
outcomes. This knowledge will inform laboratory and pilot scale process studies,
where nuisance vibrations may affect the interpretation of process outcomes, and
large scale or in situ processes in aquifers or hydrocarbon reservoirs where
imposed vibration may be deployed to improve aspects of process performance.
Future work will include miscible interface observation and quantitative
measurements in the bulk and in porous media where the roles of micro-bubbles
comprise subjects of special interest.
PMID- 26429475
TI - A new apparatus design for high temperature (up to 950 degrees C) quasi-elastic
neutron scattering in a controlled gaseous environment.
AB - A design for a sample cell system suitable for high temperature Quasi-Elastic
Neutron Scattering (QENS) experiments is presented. The apparatus was developed
at the Spallation Neutron Source in Oak Ridge National Lab where it is currently
in use. The design provides a special sample cell environment under controlled
humid or dry gas flow over a wide range of temperature up to 950 degrees C.
Using such a cell, chemical, dynamical, and physical changes can be studied in
situ under various operating conditions. While the cell combined with portable
automated gas environment system is especially useful for in situ studies of
microscopic dynamics under operational conditions that are similar to those of
solid oxide fuel cells, it can additionally be used to study a wide variety of
materials, such as high temperature proton conductors. The cell can also be used
in many different neutron experiments when a suitable sample holder material is
selected. The sample cell system has recently been used to reveal fast dynamic
processes in quasi-elastic neutron scattering experiments, which standard probes
(such as electrochemical impedance spectroscopy) could not detect. In this work,
we outline the design of the sample cell system and present results demonstrating
its abilities in high temperature QENS experiments.
PMID- 26429476
TI - Using stepped anvils to make even insulation layers in laser-heated diamond-anvil
cell samples.
AB - We describe a method to make even insulation layers for high-pressure laser
heated diamond-anvil cell samples using stepped anvils. The method works for both
single-sided and double-sided laser heating using solid or fluid insulation. The
stepped anvils are used as matched pairs or paired with a flat culet anvil to
make gasket insulation layers and not actually used at high pressures; thus,
their longevity is ensured. We compare the radial temperature gradients and Soret
diffusion of iron between self-insulating samples and samples produced with
stepped anvils and find that less pronounced Soret diffusion occurs in samples
with even insulation layers produced by stepped anvils.
PMID- 26429477
TI - New sample carrier systems for thermogravimetric analysis under forced flow
conditions and their influence on microkinetic results.
AB - For thermogravimetric analysis, it has been shown that, depending on the type of
sample container, different kinetic results could be obtained despite regarding
the same reaction under constant conditions. This is due to limiting macrokinetic
effects which are strongly dependant on the type of sample carrying system. This
prompted the need for sample containers which deliver results minimally limited
by diffusive mass transport. In this way, two container systems were developed,
both characterized by a forced flow stream through a solid, porous bed: one from
bottom to top (counter-current flow) and one from top to bottom (co-current
flow). Optical test measurements were performed, the results indicating that
reaction proceedings are almost fully independent of the geometrical shape of the
sample containers. The Boudouard reaction was investigated with a standard
crucible and the new developed systems; the reaction rates determined differed
significantly, up to a factor of 6.2 at 1373 K.
PMID- 26429478
TI - Development of a high magnetic field assisted pulsed laser deposition system.
AB - A high magnetic field assisted pulsed laser deposition (HMF-PLD) system has been
developed to in situ grow thin films in a high magnetic field up to 10 T. In this
system, a specially designed PLD cylindrical vacuum chamber is horizontally
located in the bore configuration of a superconducting magnet with a bore
diameter of 200 mm. To adjust the focused pulsed laser into the target in such a
narrow PLD vacuum chamber, an ingeniously built-in laser leading-in chamber is
employed, including a laser mirror with a reflection angle of 65 degrees and a
damage threshold up to 3.4 J/cm(2). A laser alignment system consisting of a
built-in video-unit leading-in chamber and a low-energy alignment laser is
applied to monitor and align the pulsed laser propagation in the PLD vacuum
chamber. We have grown La0.7Sr0.3MnO3 (LSMO) thin films on
(LaAlO3)0.3(Sr2AlTaO6)0.7 (001) [LSAT (001)] substrates by HMF-PLD. The results
show that the nanostructures of the LSMO films can be tuned from an epitaxially
continuous film structure without field to a vertically aligned nanorod structure
with an applied high magnetic field above 5 T, and the dimension size of the
nanorods can be tuned by the strength of the magnetic field. The associated
magnetic anisotropy is found to be highly dependent on the nanorod structures. We
show how the HMF-PLD provides an effective route toward tuning the nanostructures
and the physical properties of functional thin films, giving it an important role
in development of nanodevices and their application.
PMID- 26429479
TI - Microscopic observation of magnetic bacteria in the magnetic field of a rotating
permanent magnet.
AB - Magnetotactic bacteria are ubiquitous and can be found in both freshwater and
marine environments. Due to intracellular chains of magnetic single domain
particles, they behave like swimming compass needles. In external magnetic fields
like the Earth's magnetic field, a torque is acting on the chain. This will cause
the bacterium to be rotated and aligned with the external field. The swimming
direction of magnetotactic bacteria can be controlled with external magnetic
fields, which makes it convenient to study them under a light microscope.
Usually, a special set of coils arranged around a light microscope is used to
control the swimming magnetotactic bacteria. Here, we present a simple mechanical
system with a permanent magnet, which produces a rotating magnetic field of
nearly constant amplitude in the focal plane of a light microscope. The device is
placed beside the light microscope and easily adaptable to almost any microscope
and thus convenient for field experiments. To describe the trajectories
qualitatively, a theoretical model of the trajectories is presented. This device
can be used to control the swimming direction of magnetotactic bacteria and also
for studying their magnetic and hydrodynamic properties.
PMID- 26429480
TI - Design of a simple, lightweight, passive-elastic ankle exoskeleton supporting
ankle joint stiffness.
AB - In this study, a passive-elastic ankle exoskeleton (PEAX) with a one-way clutch
mechanism was developed and then pilot-tested with vertical jumping to determine
whether the PEAX is sufficiently lightweight and comfortable to be used in
further biomechanical studies. The PEAX was designed to supplement the function
of the Achilles tendon and ligaments as they passively support the ankle torque
with their inherent stiffness. The main frame of the PEAX consists of upper and
lower parts connected to each other by tension springs (N = 3) and lubricated
hinge joints. The upper part has an offset angle of 5 degrees with respect to
the vertical line when the springs are in their resting state. Each spring has a
slack length of 8 cm and connects the upper part to the tailrod of the lower part
in the neutral position. The tailrod freely rotates with low friction but has a
limited range of motion due to the stop pin working as a one-way clutch. Because
of the one-way clutch system, the tension springs store the elastic energy only
due to an ankle dorsiflexion when triggered by the stop pin. This clutch
mechanism also has the advantage of preventing any inconvenience during ankle
plantarflexion because it does not limit the ankle joint motion during the
plantarflexion phase. In pilot jumping tests, all of the subjects reported that
the PEAX was comfortable for jumping due to its lightweight (approximately 1 kg)
and compact (firmly integrated with shoes) design, and subjects were able to
nearly reach their maximum vertical jump heights while wearing the PEAX. During
the countermovement jump, elastic energy was stored during dorsiflexion by spring
extension and released during plantarflexion by spring restoration, indicating
that the passive spring torque (i.e., supportive torque) generated by the ankle
exoskeleton partially supported the ankle joint torque throughout the process.
PMID- 26429481
TI - Enhanced analogue front-end for the measurement of the high state of wide-band
voltage pulses with 87 dB common-mode rejection ratio and +/-0.65 ppm 1-day
offset stability.
AB - An improved analogue front-end for measuring the high state of trapezoidal
voltage pulses with transition duration of 3 MUs is presented. A new measurement
system, composed by a front-end and the state-of-the-art acquisition board NI PXI
5922, has been realized with improved Common Mode Rejection Ratio (CMRR) of more
than 87 dB at DC and 3-sigma stability of +/-0.65 ppm over 1 day. After
highlighting the main design enhancements with respect to state-of-the-art
solutions, the CMRR measurement is reported. The output drift due to temperature
and humidity is assessed to be negligible. Finally, the worst-case repeatability
is measured both with shorted-to-ground inputs and with an applied common-mode
voltage of 10 V, which represents the nominal working condition.
PMID- 26429482
TI - Stiffness modeling of compliant parallel mechanisms and applications in the
performance analysis of a decoupled parallel compliant stage.
AB - This paper investigates the stiffness modeling of compliant parallel mechanism
(CPM) based on the matrix method. First, the general compliance matrix of a
serial flexure chain is derived. The stiffness modeling of CPMs is next discussed
in detail, considering the relative positions of the applied load and the
selected displacement output point. The derived stiffness models have simple and
explicit forms, and the input, output, and coupling stiffness matrices of the CPM
can easily be obtained. The proposed analytical model is applied to the stiffness
modeling and performance analysis of an XY parallel compliant stage with input
and output decoupling characteristics. Then, the key geometrical parameters of
the stage are optimized to obtain the minimum input decoupling degree. Finally, a
prototype of the compliant stage is developed and its input axial stiffness,
coupling characteristics, positioning resolution, and circular contouring
performance are tested. The results demonstrate the excellent performance of the
compliant stage and verify the effectiveness of the proposed theoretical model.
The general stiffness models provided in this paper will be helpful for
performance analysis, especially in determining coupling characteristics, and the
structure optimization of the CPM.
PMID- 26429483
TI - An ultra-high vacuum chamber for scattering experiments featuring in-vacuum
continuous in-plane variation of the angle between entrance and exit vacuum
ports.
AB - A concept that enables in-vacuum continuous variation of the angle between two
ports in one plane has been developed and implemented. The vacuum chamber allows
for measuring scattering cross sections as a function of scattering angle and is
intended for resonant inelastic X-ray scattering experiments. The angle between
the ports can be varied in the range of 30 degrees -150 degrees , while the
pressure change is less than 2 * 10(-10) mbars.
PMID- 26429484
TI - Point contact tunneling spectroscopy apparatus for large scale mapping of surface
superconducting properties.
AB - We describe the design and testing of a point contact tunneling spectroscopy
device that can measure material surface superconducting properties (i.e., the
superconducting gap Delta and the critical temperature T(C)) and density of
states over large surface areas with size up to mm(2). The tip lateral (X,Y)
motion, mounted on a (X,Y,Z) piezo-stage, was calibrated on a patterned substrate
consisting of Nb lines sputtered on a gold film using both normal (Al) and
superconducting (PbSn) tips at 1.5 K. The tip vertical (Z) motion control enables
some adjustment of the tip-sample junction resistance that can be measured over 7
orders of magnitudes from a quasi-ohmic regime (few hundred Omega) to the tunnel
regime (from tens of kOmega up to few GOmega). The low noise electronic and
LabVIEW program interface are also presented. The point contact regime and the
large-scale motion capabilities are of particular interest for mapping and
testing the superconducting properties of macroscopic scale superconductor-based
devices.
PMID- 26429485
TI - Deformation behavior of micro-indentation defects under uniaxial and biaxial
loads.
AB - The microdefects of structure frequently act as the source to generate initial
cracks and lead to the fracture failure. Study on the deformation behaviors of
embedded defects would be conducive to better understand the failure mechanisms
of structural materials. Micro-indentation technique was applied to prepare the
initial indentations as embedded surface defects at the gauge length section and
central section of a cross-shaped AZ31B magnesium alloy specimen. A novel in situ
biaxial tensile device was developed to apply the synchronous biaxial loads. Via
the observation by an optical microscope with three-dimensional imaging and
measurement functions, the changing laws of the indentation topographies under
uniaxial and biaxial tensile loads were discussed. Compared with the gauge length
section, the increasing trend of the indentation length of the central section
was relatively flat, and the decreasing trend of the indentation depth was more
significant. The changes of indentation topographies were explained by the
Poisson effect, and the significant plastic tensile stress has led to the
releasing of the residual stress around the indentation location and also
promoted the planarization of the pileup.
PMID- 26429486
TI - Industry-relevant magnetron sputtering and cathodic arc ultra-high vacuum
deposition system for in situ x-ray diffraction studies of thin film growth using
high energy synchrotron radiation.
AB - We present an industry-relevant, large-scale, ultra-high vacuum (UHV) magnetron
sputtering and cathodic arc deposition system purposefully designed for time
resolved in situ thin film deposition/annealing studies using high-energy (>50
keV), high photon flux (>10(12) ph/s) synchrotron radiation. The high photon
flux, combined with a fast-acquisition-time (<1 s) two-dimensional (2D) detector,
permits time-resolved in situ structural analysis of thin film formation
processes. The high-energy synchrotron-radiation based x-rays result in small
scattering angles (<11 degrees ), allowing large areas of reciprocal space to be
imaged with a 2D detector. The system has been designed for use on the 1-tonne,
ultra-high load, high-resolution hexapod at the P07 High Energy Materials Science
beamline at PETRA III at the Deutsches Elektronen-Synchrotron in Hamburg,
Germany. The deposition system includes standard features of a typical UHV
deposition system plus a range of special features suited for synchrotron
radiation studies and industry-relevant processes. We openly encourage the
materials research community to contact us for collaborative opportunities using
this unique and versatile scientific instrument.
PMID- 26429487
TI - A novel compact three-dimensional laser-sintered collimator for neutron
scattering.
AB - Improvements in the available flux at neutron sources are making it increasingly
feasible to obtain refineable neutron diffraction data from samples smaller than
1 mm(3). The signal is typically too weak to introduce any further sample
environment in the 30-50 mm diameter surrounding the sample (such as the walls of
a pressure cell) due to the high ratio of background to sample signal, such that
even longer count times fail to reveal reflections from the sample. Many neutron
instruments incorporate collimators to reduce parasitic scattering from the
instrument and from any surrounding material and larger pieces of sample
environment, such as cryostats. However, conventional collimation is limited in
the volume it can focus on due to difficulties in producing tightly spaced
neutron-absorbing foils close to the sample and in integrating this into neutron
instruments. Here we present the design of a novel compact 3D rapid-prototyped
(or "printed") collimator which reduces these limitations and is shown to improve
the ratio of signal to background, opening up the feasibility of using additional
sample environment for neutron diffraction from small sample volumes. The
compactness and ease of customisation of the design allows this concept to be
integrated with existing sample environment and with designs that can be tailored
to individual detector geometries without the need to alter the setup of the
instrument. Results from online testing of a prototype collimator are presented.
The proof of concept shows that there are many additional collimator designs
which may be manufactured relatively inexpensively, with a broad range of
customisation, and geometries otherwise impossible to manufacture by conventional
techniques.
PMID- 26429488
TI - Note: Design and fabrication of a simple versatile microelectrochemical cell and
its accessories.
AB - A microelectrochemical cell housed in an optical microscope and custom-made
accessories have been designed and fabricated, which allows performing spatially
resolved corrosion measurements. The cell assembly was designed to directly
integrate the reference electrode close to the capillary tip to avoid air
bubbles. A hard disk along with an old optical microscope was re-engineered into
a microgrinder, which made the vertical grinding of glass capillary tips very
easy. A stepper motor was customized into a microsyringe pump to dispense a
controlled volume of electrolyte through the capillary. A force sensitive
resistor was used to achieve constant wetting area. The functionality of the
developed instrument is demonstrated by studying MU-electrochemical behavior of
worn surface on AA2014-T6 alloy.
PMID- 26429489
TI - Note: Design and realization of a portable edge illumination X-ray phase contrast
imaging system.
AB - We discuss a portable edge illumination x-ray phase contrast imaging system based
on compact piezoelectric motors, which enables its transportation to different
environments, e.g., hosting different x-ray source technologies. The analysis of
images of standard samples reveals an angular sensitivity of 270 +/- 6 nrad,
which compares well with the 260 +/- 10 nrad reported for previous systems based
on stepper motors, demonstrating that system portability can be achieved without
affecting phase sensitivity. The results can also be considered a test of the
performance of the piezoelectric motors, and as such could be of interest to
researchers planning their use in other imaging systems.
PMID- 26429490
TI - Note: Utilization of polymer gel as a bolus compensator and a dosimeter in the
near-surface buildup region for breast-conserving therapy.
AB - Tangential beam radiotherapy is routinely used for radiation therapy after breast
conserving surgery. A tissue-equivalent bolus placed on the irradiated area
shifts the depth of the dose distribution; this bolus provides uniform dose
distribution to the breast. The gel bolus made by the BANG-Pro((r)) polymer gel
and in an oxygen non-transmission pack was applicable as a dosimeter to measure
dose distribution in near-surface buildup region. We validated the use of the gel
bolus to improve in the whole-breast/chest wall, including the near-surface
buildup region.
PMID- 26429491
TI - Note: A small roll angle measurement method with enhanced resolution based on a
heterodyne interferometer.
AB - Small roll angle is hard to be measured directly by commercial interferometer
instruments due to their low sensitivities in axial direction. A method for its
measurement based on a heterodyne interferometer is presented, which adopts
accessories including a half wave plate, a multiple-reflector, and a phase meter
to achieve test by detecting phase differences between the measurement and
reference arms. Mathematical model reveals the resolution will be improved by
increasing pass times through the half wave plate. The theoretical resolution is
up to 0.19 in. when the pass times increase to three and the phase meter
resolution is 0.01 degrees . The proposed method is proved by the experiment.
PMID- 26429492
TI - Note: Detector collimators for the nanoscale ordered materials diffractometer
instrument at the Spallation Neutron Source.
AB - Five neutron collimator designs were constructed and tested at the nanoscale
ordered materials diffractometer (NOMAD) instrument. Collimators were made from
High Density PolyEthylene (HDPE) or 5% borated HDPE. In all cases, collimators
improved the signal to background ratio and reduced detection of secondary
scattering. In the Q-range 10-20 A(-1), signal to background ratio improved by
factors of approximately 1.6 and 2.0 for 50 and 100 mm deep collimators,
respectively. In the Q-range 40-50 A(-1), the improvement factors were 1.8 and
2.7. Secondary scattering as measured at Q ~ 9.5 A(-1) was significantly
decreased when the collimators were installed.
PMID- 26429493
TI - Note: A resonating reflector-based optical system for motion measurement in micro
cantilever arrays.
AB - A robust, compact optical measurement unit for motion measurement in micro
cantilever arrays enables development of portable micro-cantilever sensors. This
paper reports on an optical beam deflection-based system to measure the
deflection of micro-cantilevers in an array that employs a single laser source, a
single detector, and a resonating reflector to scan the measurement laser across
the array. A strategy is also proposed to extract the deflection of individual
cantilevers from the acquired data. The proposed system and measurement strategy
are experimentally evaluated and demonstrated to measure motion of multiple
cantilevers in an array.
PMID- 26429494
TI - Note: Model-based identification method of a cable-driven wearable device for arm
rehabilitation.
AB - Cable-driven exoskeletons have used active cables to actuate the system and are
worn on subjects to provide motion assistance. However, this kind of wearable
devices usually contains uncertain kinematic parameters. In this paper, a model
based identification method has been proposed for a cable-driven arm exoskeleton
to estimate its uncertainties. The identification method is based on the
linearized error model derived from the kinematics of the exoskeleton. Experiment
has been conducted to demonstrate the feasibility of the proposed model-based
method in practical application.
PMID- 26429495
TI - Note: Directly measuring the direct digital synthesizer frequency chirp-rate for
an atom interferometer.
AB - During gravity measurements with Raman type atom interferometry, the frequency of
the laser used to drive Raman transition is scanned by chirping the frequency of
a direct digital synthesizer (DDS), and the local gravity is determined by
precisely measuring the chip rate alpha of DDS. We present an effective method
that can directly evaluate the frequency chirp rate stability of our DDS. By
mixing a pair of synchronous linear sweeping signals, the chirp rate fluctuation
is precisely measured with a frequency counter. The measurement result shows that
the relative alpha instability can reach 5.7 * 10(-11) in 1 s, which is
neglectable in a 10(-9) g level atom interferometry gravimeter.
PMID- 26429496
TI - Note: Resonance magnetoelectric interactions in laminate of FeCuNbSiB and
multilayer piezoelectric stack for magnetic sensor.
AB - This paper develops a simple miniature magnetoelectric (ME) laminate
FeCuNbSiB/PZT-stack made up of magnetostrictive Fe73.5Cu1Nb3Si13.5B9 (FeCuNbSiB)
foils and piezoelectric Pb(Zr, Ti)O3 (PZT) multilayer stack vibrator. Resonant ME
interactions of FeCuNbSiB/PZT-stack with different layers of FeCuNbSiB foil (L)
are investigated in detail. The experimental results show that the ME voltage
coefficient reaches maximum value of 141.5 (V/cm Oe) for FeCuNbSiB/PZT-stack with
L = 6. The AC-magnetic sensitivities can reach 524.29 mV/Oe and 1.8 mV/Oe under
resonance 91.6 kHz and off-resonance 1 kHz, respectively. The FeCuNbSiB/PZT-stack
can distinguish small dc-magnetic field of ~9 nT. The results indicate that the
proposed ME composites are very promising for the cheap room-temperature magnetic
field sensing technology.
PMID- 26429497
TI - Note: An improved 3D imaging system for electron-electron coincidence
measurements.
AB - We demonstrate an improved imaging system that can achieve highly efficient 3D
detection of two electrons in coincidence. The imaging system is based on a fast
frame complementary metal-oxide semiconductor camera and a high-speed waveform
digitizer. We have shown previously that this detection system is capable of 3D
detection of ions and electrons with good temporal and spatial resolution. Here,
we show that with a new timing analysis algorithm, this system can achieve an
unprecedented dead-time (<0.7 ns) and dead-space (<1 mm) when detecting two
electrons. A true zero dead-time detection is also demonstrated.
PMID- 26429498
TI - Note: Design of a laser feedback interferometer with double diffraction system.
AB - A novel laser feedback interferometer with double diffraction system is proposed
in this paper. A beam emitted from the laser is incident onto a transmission
grating. The mth order beam is vertically reflected by a mirror and diffracted
again by the grating. The double-diffracted beam returns into the laser cavity
and mixes with the light inside the active cavity, thus generating a modulation
of both the amplitude and the frequency of the lasing field. Theoretical analysis
and experimental observations show that the output signal of the proposed system
depends on the grating pitch and the direction of the phase movement can be
obtained from inclination of the interference signal. It provides a potential
displacement sensor with high stability and quite a compact configuration.
PMID- 26429500
TI - Adaptive Designs with Discrete Test Statistics and Consideration of Overrunning.
AB - BACKGROUND: Interim analyses are used in clinical trials in order to enable early
decisions for medical, ethical, and economic reasons. However, it appears
unfeasible to stop a trial during such an interim analysis. New patients will
thus enter the trial while the interim analysis is ongoing. Moreover, depending
on the event kinetics of the specific disease, the trial design, and the
corresponding endpoints, some patients might still be unevaluable at the interim
analysis due to not yet completed follow-up. Occurrence of these types of
patients is characteristic for sequentially analyzed trials. Such patients are
referred to as interim patients. In trials with multiple primary endpoints,
another type of interim patients occurs. If some but not all null hypotheses can
be rejected at the interim analysis, the trial might be continued to a second
stage in order to answer the remaining questions. These second stage patients,
however, provide new data to all trial questions including the already rejected
ones and thus formally act as interim patients regarding the already rejected
null hypotheses. Although all kinds of interim patients are not part of the
interim analysis, the data collected on those patients have to be sent to the
office of regulatory affairs and will be analyzed. If a smaller or contrasting
treatment effect is observed in interim patients, this might lead to a withdrawal
of an earlier superiority proof. OBJECTIVES: Presently, interim patients and
their data are usually not considered in the confirmatory test. We offer a
strategy to deal with interim patients in sequentially analyzed trials with
discrete test statistics. The method covers sequentially analyzed single- and
multi-arm trials with one or multiple primary endpoints. METHODS: When planning
adaptive designs, it is common practice to assume that the stage-wise p-values
are independent and standard uniformly distributed under the null hypothesis. In
the context of discrete test statistics, this implies conservative tests. We
provide an algorithm which iteratively optimizes an initially given design while
adjusting for both discreteness of test statistics and interim patients. The
algorithm is described verbally, graphically and formally to facilitate immediate
implementation in computer software. RESULTS: The optimized design exploits the
aspired significance level better and is more powerful than the initial one. The
algorithm applies to fixed sample and planned flexible adaptive designs for
single- and multi-arm trials with one or multiple primary endpoints. The benefit
increases with the number of interim patients. CONCLUSIONS: When planning a trial
with interim analyses, the rules for decisions must be adjusted to interim
patients. Otherwise, the test procedure is conservative resulting in loss of
power. This is essential in situations where the number of interim patients is
important compared to the first stage, particularly in trials with multiple
primary endpoints.
PMID- 26429501
TI - 3D Light-Sheet Fluorescence Microscopy of Cranial Neurons and Vasculature during
Zebrafish Embryogenesis.
AB - Precise 3D spatial mapping of cells and their connections within living tissues
is required to fully understand developmental processes and neural activities.
Zebrafish embryos are relatively small and optically transparent, making them the
vertebrate model of choice for live in vivo imaging. However, embryonic brains
cannot be imaged in their entirety by confocal or two-photon microscopy due to
limitations in optical range and scanning speed. Here, we use light-sheet
fluorescence microscopy to overcome these limitations and image the entire head
of live transgenic zebrafish embryos. We simultaneously imaged cranial neurons
and blood vessels during embryogenesis, generating comprehensive 3D maps that
provide insight into the coordinated morphogenesis of the nervous system and
vasculature during early development. In addition, blood cells circulating
through the entire head, vagal and cardiac vasculature were also visualized at
high resolution in a 3D movie. These data provide the foundation for the
construction of a complete 4D atlas of zebrafish embryogenesis and neural
activity.
PMID- 26429503
TI - Reinforcing cerclage for a short cervix at follow-up after the primary cerclage
procedure.
AB - OBJECTIVE: To determine whether a reinforcing cerclage (RC) for a short cervix
measured after the primary cerclage procedure prolonged pregnancy. METHODS: We
conducted a retrospective cohort study of 157 women with singleton gestations who
underwent cerclage for standard indications. Women were grouped according to
cervical length (CL) at the time of follow-up 1-2 weeks after the initial
cerclage placement: >=25 mm (106 women) and <25 mm with (20 women) or without RC
(31 women). Gestational age (GA) at delivery was compared by ANOVA. Survival risk
analysis was applied to model GA at delivery adjusted for indication and CL
before and after the first cerclage. RESULTS: Women with CL >=25mm delivered
later than women with CL < 25mm after the first cerclage (p < 0.01). RC did not
delay delivery for women with CL < 25 mm (p = 0.17) after the primary procedure.
Indication for the primary cerclage (p < 0.01) and CL (p < 0.01) after the
primary cerclage were the best predictors for GA at delivery. CONCLUSION:
Placement of RC for short cervix did not prolong duration of pregnancy, GA at
delivery or modify the probability of preterm birth.
PMID- 26429502
TI - NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization.
AB - Macrophages are divided into two subpopulations: classically activated
macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli
Calmette-GuC)rin) activates disabled naC/ve macrophages to M1 macrophages, which
act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact
and/or the release of soluble factors. Various transcription factors and
signaling pathways are involved in the regulation of macrophage activation and
polarization. We discovered that BCG-activated macrophages (BAM) expressed a new
molecule, and we named it Novel Macrophage Activated Associated Protein 1
(NMAAP1). The current study found that the overexpression of NMAAP1 in
macrophages results in M1 polarization with increased expression levels of M1
genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor
alpha (TNF-N1), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte
chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-1N2), and decreased
expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor
of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1
(Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-N2) and found
in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7
cell line increased cytotoxicity against MCA207 tumor cells, which depends on
increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also
substantially enhanced the phagocytic ability of macrophages, which implies that
NMAAP1 promoted macrophage adhesive and clearance activities. Our results
indicate that NMAAP1 is an essential molecule that modulates macrophages
phenotype and plays an important role in macrophage tumoricidal functions.
PMID- 26429504
TI - A structural model for multimodular NRPS assembly lines.
AB - This viewpoint article focuses on the structures of the dissected catalytic
domains of non-ribosomal peptide synthetases (NRPSs) associated with substrate
selection and activation (A domain), substrate shuttling among the active sites
(PCP domain), peptide bond formation (C domain) and product release (TE domain).
Structural details of these essential components of the NRPS machinery,
integrated in a didomain (PCP-C) and an elongation module (C-A-PCP), were used to
generate a model for a multimodular NRPS assembly line.
PMID- 26429506
TI - The safety of treatments for angioedema with hereditary C1 inhibitor deficiency.
AB - INTRODUCTION: Angioedema is a localized and self-limiting edema of the
subcutaneous and submucosal tissue. Hereditary angioedema with C1 inhibitor
deficiency (C1-INH-HAE) is the best characterized form of hereditary angioedema.
In C1-INH-HAE, the reduced plasma levels of C1-INH cause instability of the
contact system with release of bradykinin, the key mediator of angioedema. C1-INH
HAE is characterized by recurrent skin swelling, abdominal pain, and potentially
life-threatening upper airways obstruction. Knowledge of the molecular mechanisms
leading from C1-INH deficiency to angioedema allowed the development of several
therapies. AREAS COVERED: The aim of this review article is to discuss the safety
of currently available treatments of C1-INH-HAE. The authors give an insight on
the mechanism of action and safety profile of drugs for treatment of acute
attacks and for short- and long-term prophylaxis. Evidence from systematic
reviews, clinical trials, retrospective studies, and case reports is summarized
in this review. EXPERT OPINION: C1-INH-HAE is a disabling, life-threatening
condition that lasts life-long. Different therapeutic approaches with different
drugs provide significant benefit to patients. Safety profiles of these therapies
are critical for optimal therapeutic decision and need to be known by C1-INH-HAE
treating physicians for appropriate risk/benefit evaluation.
PMID- 26429505
TI - Fatigue induced changes in conical implant-abutment connections.
AB - OBJECTIVES: Based on the current lack of data and understanding of the wear
behavior of dental two-piece implants, this study aims for evaluating the
microgap formation and wear pattern of different implants in the course of cyclic
loading. METHODS: Several implant systems with different conical implant-abutment
interfaces were purchased. The implants were first evaluated using synchrotron X
ray high-resolution radiography (SRX) and scanning electron microscopy (SEM). The
implant-abutment assemblies were then subjected to cyclic loading at 98N and
their microgap was evaluated after 100,000, 200,000 and 1 million cycles using
SRX, synchrotron micro-tomography (MUCT). Wear mechanisms of the implant-abutment
connection (IAC) after 200,000 cycles and 1 million cycles were further
characterized using SEM. RESULTS: All implants exhibit a microgap between the
implant and abutment prior to loading. The gap size increased with cyclic loading
with its changes being significantly higher within the first 200,000 cycles. Wear
was seen in all implants regardless of their interface design. The wear pattern
comprised adhesive wear and fretting. Wear behavior changed when a different
mounting medium was used (brass vs. polymer). SIGNIFICANCE: A micromotion of the
abutment during cyclic loading can induce wear and wear particles in conical
dental implant systems. This feature accompanied with the formation of a microgap
at the IAC is highly relevant for the longevity of the implants.
PMID- 26429507
TI - Management of complex anal fistulae.
PMID- 26429508
TI - Acute diverticulitis: a complex management challenge.
PMID- 26429509
TI - Challenges in the management of invasive pulmonary zygomycosis: the Alfred
experience.
PMID- 26429510
TI - Novel method of surgical mask tying to prevent spectacle slippage.
PMID- 26429511
TI - Response to Re: Role of inflammatory markers as predictors of laparotomy in
patients presenting with acute abdomen.
PMID- 26429512
TI - Re: Role of inflammatory markers as predictors of laparotomy in patients
presenting with acute abdomen.
PMID- 26429513
TI - Incidence of gallbladder torsion in acute cholecystectomy patients.
PMID- 26429514
TI - Report card from the 'ragged' school of anatomy.
PMID- 26429515
TI - Ultra-Tuning of the Rare-Earth fcu-MOF Aperture Size for Selective Molecular
Exclusion of Branched Paraffins.
AB - Using isoreticular chemistry allows the design and construction of a new rare
earth metal (RE) fcu-MOF with a suitable aperture size for practical steric
adsorptive separations. The judicious choice of a relatively short organic
building block, namely fumarate, to bridge the 12-connected RE hexanuclear
clusters has afforded the contraction of the well-defined RE-fcu-MOF triangular
window aperture, the sole access to the two interconnected octahedral and
tetrahedral cages. The newly constructed RE (Y(3+) and Tb(3+)) fcu-MOF analogues
display unprecedented total exclusion of branched paraffins from normal
paraffins. The resultant window aperture size of about 4.7 A, regarded as a
sorbate-size cut-off, enabled a complete sieving of branched paraffins from
normal paraffins. The results are supported by collective single gas and mixed
gas/vapor adsorption and calorimetric studies.
PMID- 26429518
TI - Editorial overview: New technologies.
PMID- 26429519
TI - Occurrence of otitis media in children and assessment of treatment options.
PMID- 26429521
TI - The impact of hydroxychloroquine treatment on pregnancy outcome in women with
antiphospholipid antibodies.
AB - BACKGROUND: Antiphospholipid syndrome is defined by the combination of thrombotic
events and/or obstetric morbidity in patients who have tested positive
persistently for antiphospholipid antibodies. With good treatment, approximately
70% of pregnant women with antiphospholipid syndrome will deliver a viable live
infant. However, current management does not prevent all maternal, fetal, and
neonatal complications of antiphospholipid syndrome. OBJECTIVES: This
observational, retrospective, single-center cohort study aimed to assess
pregnancy outcome in women with antiphospholipid antibodies who were treated with
hydroxychloroquine in addition to conventional treatment during pregnancy. STUDY
DESIGN: One-hundred seventy pregnancies in 96 women with persistent
antiphospholipid antibodies were analyzed: (1) 51 pregnancies that occurred in 31
women were treated with hydroxychloroquine for at least 6 months before
pregnancy, and the therapy continued throughout gestation (group A); (2) 119
pregnancies that occurred in 65 women with antiphospholipid antibodies that were
not treated with hydroxychloroquine were included as controls (group B). RESULTS:
Hydroxychloroquine-treatment was associated with a higher rate of live births
(67% group A vs 57% group B; P = .05) and a lower prevalence of antiphospholipid
antibodies-related pregnancy morbidity (47% group A vs 63% B; P = .004). The
association of hydroxychloroquine with a lower rate of any complication in
pregnancy was confirmed after multivariate analysis (odds ratio, 2.2; 95%
confidence interval, 1.2-136; P = .04). Fetal losses at >10 weeks of gestation
(2% vs 11%; P = .05) and placenta-mediated complications (2% vs 11%; P = .05)
were less frequent in group A than group B. Pregnancy duration was longer in
group A than group B (27.6 [6-40] vs 21.5 [6-40] weeks; P = .03). There was a
higher rate of spontaneous vaginal labor in hydroxychloroquine-treated women
compared with group B (37.3% vs 14.3%; P = .01). CONCLUSIONS: Despite the
heterogeneity in the 2 groups in terms of systemic lupus erythematosus prevalence
and previous pregnancy history, our results support the concept that women with
antiphospholipid antibodies may benefit from treatment with hydroxychloroquine
during pregnancy to improve pregnancy outcome. The addition of hydroxychloroquine
to conventional treatment is worthy of further assessment in a proper designed
randomized controlled trial.
PMID- 26429520
TI - Bronchopulmonary infection-colonization patterns in Spanish cystic fibrosis
patients: Results from a national multicenter study.
AB - BACKGROUND: Clinical and demographical knowledge on Spanish cystic fibrosis (CF)
patients is incomplete as no national registry exists. CF-microbiology has not
been studied at national level. The results of the first Spanish multicenter
study on CF microbiology are presented. METHODS: 24 CF-Units for adult (n=12) and
pediatric (n=12) patients from 17 hospitals provided sputa and clinical data from
15 consecutive patients. Cultures and susceptibility testing were performed.
Colonization impact on pulmonary function was assessed. RESULTS: 341 patients
[mean (SD) age 21 (11) years, 180>=18years, mean (SD) FEV1=68 (25)%] were
included. Pseudomonas aeruginosa was reported as chronic, intermittent or absent
in 46%, 22% and 32% of patients, respectively. The annual prevalence was 62%.
Positive P. aeruginosa and methicillin-resistant Staphylococcus aureus cultures
were significantly associated with lower FEV1 (p<0.001 and p=0.003,
respectively). CONCLUSIONS: The representative subset of the Spanish CF
population which has been clinically, demographically and microbiologically
characterized will serve as a reference for future CF studies in Spain.
PMID- 26429522
TI - Tamsulosin does not increase 1-week passage rate of ureteral stones in ED
patients.
AB - OBJECTIVE: The objective of the study is to determine if tamsulosin initiated in
the emergency department (ED) decreases the time to ureteral stone passage at 1
week or time to pain resolution, compared to placebo. METHODS: We performed a
prospective, randomized, double-blinded, placebo-controlled trial of tamsulosin
vs placebo in ED patients with ureterolithiasis on computed tomography. Patients
were identified and enrolled between April 2007 and February 2009 and were
randomized to either 0.4 mg of tamsulosin or placebo for 1 week. We contacted
participants using a telephone survey on post-ED visit days 1, 2, 3, and 7. The
primary outcome was time to stone passage, with secondary outcomes being maximum
pain score and amount of pain medication required. RESULTS: Of the 127 patients
enrolled during this study, 15 were lost to follow-up, and 12 required surgical
interventions before the 7-day mark, leaving 100 patients for analysis. Of the
100 patients, 53 received tamsulosin and 47 received placebo. There was no
difference between groups in percentage of male, mean age, initial serum
creatinine, average stone size, stone location, and history of prior stone. The
probability that the patient did not pass a stone at 7 days was not different
between tamsulosin and placebo, 62.1% (95% confidence interval, 49.1%-75.1%) vs
54.4% (95% confidence interval, 40.3%-68.6%; P = .58). There was no significant
difference in the high pain score (P = .12) or hydrocodone/acetaminophen intake
(P = .76) between treatment groups at any of the time points. CONCLUSION: This
study reveals no difference in the proportion of stone passage or high pain score
and pain medication utilization at 7 days between tamsulosin and placebo.
PMID- 26429523
TI - Chloroquine and Hydroxychloroquine Are Novel Inhibitors of Human Organic Anion
Transporting Polypeptide 1A2.
AB - Chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used to treat malaria
and inflammatory diseases, long-term usage of which often causes severe side
effects, especially retinopathy. Solute carrier transporters (SLCs) are important
proteins responsible for the cellular uptake of endogenous and exogenous
substances. Inhibitors competing with transporter substrates for SLCs often
results in unfavorable toxicities and unsatisfactory therapeutic outcomes. We
investigated the inhibitory effect of CQ and HCQ on substrate uptake mediated
through a range of important SLC transporters in overexpressing human embryonic
kidney (HEK293) cells. Our data revealed that both CQ and HCQ potently inhibit
the uptake activity of organic anion transporting polypeptide 1A2 (OATP1A2). We
recently reported OATP1A2 to be expressed in human retinal pigment epithelium
(RPE), where it mediates cellular uptake of all-trans-retinol (atROL), a key step
in the classical visual cycle. In this study, we demonstrate that CQ and HCQ
could markedly impair atROL uptake in OATP1A2-expressing HEK293 cells and more
importantly, in primary human RPE cells. Our study shows that CQ and HCQ are
novel inhibitors of OATP1A2 and significantly impair OATP1A2-mediated substrate
uptake, particularly transport of atROL into the RPE. This effect may compromise
the function of the classic visual cycle leading to vision impairment and
contribute to the retinopathy observed clinically in patients using CQ or HCQ.
PMID- 26429524
TI - Ultrasound and physical models shed light on the respiratory system of embryonic
dogfishes.
AB - Embryos of live-bearing elasmobranchs (sharks, skates, and rays) must acquire
oxygen in the uterus for several months to more than a year, but the mechanisms
of delivery and uptake are still largely unknown. Diagnostic sonography performed
on a captive Japanese dogfish (Squalus japonicus) showed that a late-stage embryo
used buccal movement to pump uterine fluid, suggesting that the embryo acquires
oxygen from uterine fluid via gill ventilation. It has been assumed that
embryonic respiration in aplacental sharks depends on oxygen supplied by the
uterine wall. To test this hypothesis, the rate of oxygen diffusion was estimated
by applying a physical model to the uterine wall of two dogfish species (Squalus
cf. mitsukurii and Squalus cubensis). The model calculations indicate that the
supply of oxygen via diffusion through the uterine villi contributes less than 15
30% of the total oxygen demand of late-stage embryos. Some previous authors have
suggested that pregnant dogfish intermittently exchange uterine fluid with
external seawater during late gestation. Thus, late-stage embryos may acquire
oxygen primarily from uterine seawater introduced from the external environment.
PMID- 26429525
TI - The seminal receptacle and implications for reproductive processes in the
invasive gastropod Crepidula fornicata.
AB - The calyptraeid gastropod Crepidula fornicata is the object of considerable
research attention, due to its invasive status in the North-Eastern Atlantic, its
introduction to habitats throughout the Northern hemisphere, and its scientific
interest as a model organism for the study of developmental and reproductive
processes in the Metazoa. Since the knowledge concerning the structural
foundations for its reproductive processes is surprisingly weak, we investigated
the seminal receptacle, a key structure in the reproductive biology of other
metazoans, using histology, scanning electron and transmission electron
microscopy. The seminal receptacle consists of 9-11 lobes, each subdivided into
small, narrow lobules. The inner epithelium of the lobules appears to be highly
dynamic, characterised by the perforation and attachment of received spermatozoa,
the progressive degeneration of this epithelium, and the concomitant detachment
of the spermatozoa. The allocation of spermatozoa to many different lobules, in
different phases, may explain the extended reproductive season of C. fornicata,
and thereby contribute to its colonizing and invasive success. The same
compartmentalisation, as well as the complete covering of the inner epithelium of
the lobules by spermatozoa and the large amount of spermatozoan debris in the
lumina, suggest that the C. fornicata seminal receptacle may be a site of sperm
competition in this polyandrous species.
PMID- 26429526
TI - [Effects of simulated weightlessness on biological activity of human NK cells
induced by IL-2].
AB - OBJECTIVE: To investigate the effects of simulated weightlessness on the activity
of human natural killer (NK) cells induced by interleukin 2 (IL-2). METHODS:
Primary human NK cells were cultured under simulated weightlessness condition.
The viability of NK cells was determined by CCK-8 assay; cell apoptosis was
analyzed by flow cytometry combined with annexin V-FITC/PI staining; the level of
interferon gamma (IFN-gamma) was examined by ELISA; the mRNA levels of IL-12
receptor genes were detected by reverse transcription PCR. RESULTS: Compared with
control cells cultured in normal gravity, IL-2-induced cell proliferation rate of
NK cells cultured in simulated weightlessness decreased by 13.6% and 31% at 24
and 48 hours, respectively; the cell apoptotic rate increased by 8% and 19%; IL-2
induced IFN-gamma production was inhibited by 25.2% and 47.8%; the cytotoxicity
of NK cells induced by IL-2 was reduced by 7% and 18%; IL-12-induced IFN-gamma
production was suppressed by 21.8% and 58.8% in IL-2 pretreated cells at 24 and
48 hours, respectively. In addition, the mRNA levels of IL-12 beta1 and beta2
receptor genes were significantly down-regulated in the cells cultured in
simulated weightlessness. CONCLUSION: Simulated weightlessness can inhibit the
proliferation of NK cells induced by IL-2, promote NK cell apoptosis, impair IL-2
induced IFN-gamma production and cytotoxicity in NK cells, and inhibit IL-12
induced IFN-gamma production through down-regulating IL-12 receptor gene
expression in NK cells.
PMID- 26429527
TI - [IL-37 inhibits the proliferation, invasion and migration of SMMC-7721 cells in
vitro].
AB - OBJECTIVE: To analyze the impact of interleukin-37 (IL-37) on proliferation,
migration and invasion of SMMC-7721 hepatocellular carcinoma cells and the
related molecular mechanism. METHODS: SMMC-7721 cells cultured in vitro were
divided into the (50, 100, 200, 500) ng/mL recombinant human IL-37 (rhIL-37)
treated groups and control group. Cell proliferation ability was detected by CCK
8 assay. Wound healing assay was used to observe cell migration ability.
Transwell(TM) assay was performed to test the cell invasion ability. The levels
of signal transducers and activators of transcription 3 (STAT3), phospho-STAT3 (p
STAT3) and matrix metalloproteinase-2 (MMP-2) were determined using Western
blotting. RESULTS: CCK-8 assay showed that rhIL-37 inhibited the proliferation of
SMMC-7721 cells. Wound healing assay revealed that rhIL-37 inhibited the
migration of SMMC-7721 cells. Transwell(TM) indicated that rhIL-37 inhibited the
invasion of SMMC-7721 cells. Western blotting demonstrated that rhIL-37 down
regulated the expressions of p-STAT3 and MMP-2. CONCLUSION: IL-37 can inhibit the
proliferation, migration and invasion of SMMC-7721 cells. It may be related with
the down-regulation of p-STAT3 and MMP-2.
PMID- 26429528
TI - [Over-expression of human S-phase kinase-associated protein 2 (Skp2) promotes
proliferation of MCF-7 breast cancer cells and increases the number of S phase
cells].
AB - OBJECTIVE: To construct a eukaryotic expression vector for the human gene S-phase
kinase-associated protein 2 (Skp2) with a FLAG tag (pcDNA3-FLAG-Skp2) and detect
the effect of Skp2 over-expression on the cell growth and cell cycle in MCF-7
breast cancer cells. METHODS: Skp2 was amplified from MDA-MB-231 breast cancer
cells by reverse-transcription polymerase chain reaction (RT-PCR) and then used
to construct the eukaryotic expression vector pcDNA3-FLAG-Skp2. Integration of
Skp2 into the vector was confirmed via restriction digest and sequencing; The
pcDNA3-FLAG-Skp2 was then transfected into MCF-7 breast cancer cells. Expression
of Skp2 protein was verified by Western blotting. Cell growth was assessed by
Alamar blue proliferation assay, cell cycle analysis was carried out by flow
cytometry. RESULTS: The PCR amplified fragment was matched up with the
anticipated result and its sequence was the same as the data published on
GenBank, indicating that the recombinant plasmid pcDNA3-FLAG-Skp2 was constructed
successfully. Western blotting revealed that the expression of Skp2 protein was
markedly up-regulated in the pcDNA3-FLAG-Skp2 transfected MCF-7 cells at 48
hours. Furthermore, cell growth was significantly promoted in Skp2 over-expressed
MCF-7 cells, and the cell count in S phase were also raised. CONCLUSION: The
recombinant eukaryotic expression vector pcDNA3-FLAG-Skp2 has been constructed
and expressed in MCF-7 breast cancer cells successfully. Over-expression of Skp2
resulted in the increased cell growth and number of S phase cells in Skp2
transfected MCF-7 cells.
PMID- 26429529
TI - [Culture supernatants of lymphocytes from different lymphoid tissues induce
transdifferentiation of Caco2 cells into M-like cells].
AB - OBJECTIVE: To establish the microfold (M)-like cell model in vitro and identify M
like cells through detecting the capacity of transporting fluorescent beads and
the levels of the associated genes, and to observe the effects of lymphocyte
culture supernatants stimulated by concanavalin A (Con A) from different lymphoid
tissues on the differentiation of Caco2 cells into M-like cells. METHODS: The
isolated lymphocytes of Peyer's patch (PP), mesenteric lymph node (MLN) and
spleen (Sp) were incubated with 3 MUg/mL Con A for 3 days. The culture
supernatants were collected and co-cultured with Caco2 cells. The fluorescent
bead suspension was added into the upper compartment of the TranswellTM inserts,
and then basolateral solutions were then sampled and analyzed. The number of
transported fluorescent beads was measured by flow cytometry. The expressions of
M-like cells-associated genes, such as chemokine (C-C motif) ligand 20 (CCL20),
claudin4 (CLDN4), tumor necrosis factor receptor superfamily member 9 (TNFRSF9),
and Spi-B were detected by reverse transcription PCR. RESULTS: Compared with
blank control group, the number of fluorescent beads transported by induced Caco2
cells and the levels of CCL20, CLDN4, TNFRSF9 and Spi-B mRNAs significantly
increased in induced Caco2 cells treated with the culture supernatants of
lymphocytes from PP, MLN and Sp. After Con A stimulation, the number of
fluorescent beads transported by induced Caco2 cells and the levels of CCL20,
CLDN4, TNFRSF9 and Spi-B mRNAs were higher than those in the unstimulated group.
CONCLUSION: The lymphocyte culture supernatants stimulated or unstimulated by Con
A can induce the transdifferentiation of Caco2 cells into M-like cells.
PMID- 26429530
TI - [miR-135b promotes the invasion and metastasis of hepatocellular carcinoma
cells].
AB - OBJECTIVE: To explore the effect of miR-135b on the invasion and metastasis of
hepatocellular carcinoma cells and the underlying molecular mechanism. METHODS:
The invasive and metastasis abilities were detected by Transwell(TM) assay in
hepatocellular carcinoma cells with over-expressed or down-regulated miR135b. The
hepatocellular carcinoma cell growth and tumor formation abilities in vivo were
examined by xenograft model. Downstream genes targeted by miR-135b were detected
by Western blotting and dual-luciferase report assay. RESULTS: Up-regulated miR
135b was observed in highly invasive MHCC97 hepatocellular carcinoma cell lines.
Over-expression of miR-135b enhanced the invasive and migratory abilities in
vitro and in vivo of HepG2 and Bel-7402 cells. The invasive and migratory
abilities in vitro and in vivo were significantly suppressed in miR-135b down
regulated MHCC97 hepatocellular carcinoma cells silenced by the pcDNA-miR-135b
Sponge plasmid. Western blotting and dual-luciferase report system analysis
showed that multiple key components in the Hippo pathway, including large tumor
suppressor homolog 2 (LATS2), beta-transducin repeats-containing proteins (beta
TrCP), N-myc downstream-regulated gene 2 (NDR2) as well as leucine zipper tumor
suppressor gene 1 (LZTS1) were targeted by miR-135b. CONCLUSION: miR-135b
promotes the invasion and metastasis possibly by targeting the Hippo pathway
genes.
PMID- 26429531
TI - [Inhibition of HBV replication by constructing an artificial transcription
factor].
AB - OBJECTIVE: To construct a zinc finger protein-artificial transcription factor
(ZFP-ATF) specifically bound to hepatitis B virus (HBV) enhancer 1 (Enh1), then
detect its expression in HepG2.2.15 cells, observe its effect on cell growth and
its role in inhibiting the replication and expression of HBV DNA. METHODS: The
zinc finger protein (ZFP) specifically bound to HBV Enh1 was fused with a Krvppel
associated box (KRAB) transcriptional repression domain to produce an artificial
transcription factor (ATF). After relative modification and optimization, the
synthetic ATF nucleic acid sequence was inserted into the eukaryotic expression
plasmid vector pcDNA3.1+ and its sequence was identified. Then pcDNA3.1-ATF was
transfected into HepG2.2.15 cells through X-tremeGENE HP. The expression of ATF
was detected by confocal microscope. The impact of ATF on cell growth was
measured by CCK-8 assay. The inhibitory effect on HBV DNA by ATF was assured by
real-time quantitative PCR (qRT-PCR), ELISA and Western blotting at 24, 48 and 72
hours after transfection. RESULTS: The pcDNA3.1-ATF (nls-ZFP-KRAB-FLAG)
eukaryotic expression plasmid vector was successfully constructed. ATF was
expressed in HepG2.2.15 cells as expected without obvious influence on cell
growth. ATF repressed the replication and expression of HBV DNA, especially at 72
hours post-transfection when the inhibition rate was 68%. CONCLUSION: The
synthetic ATF can be expressed in HepG2.2.15 cells normally without toxic effect
on the cells and exert an inhibitory effect on the replication and expression of
HBV DNA by specifically bound to HBV Enh1.
PMID- 26429532
TI - [Protective effect of salidroside against high altitude hypoxia-induced brain
injury in rats].
AB - OBJECTIVE: To observe the protective effect of salidroside against brain injury
in rats exposed to hypobaric hypoxia, and investigate the molecular mechanism of
salidroside in the prevention of hypobaric hypoxia-induced brain injury. METHODS:
Rats were placed in experiment module simulating 6000 m altitude to establish
acute hypobaric hypoxia-induced brain injury models. Their respiratory frequency
was observed and recorded. Cell apoptosis in the hippocampal dentate gyrus (DG)
was detected by TUNEL assay; the expressions of Ras homolog family member A
(RhoA), phosphorylated extracellular signal-regulated kinase (p-ERK) and
phosphorylated c-Jun N-terminal kinase (p-JNK) were detected by Western blotting.
RESULTS: After acute exposure to 6000 m altitude, the respiratory frequency of
the rats increased remarkably. The simulation of hypobaric hypoxia induced cell
apoptosis in hippocampal DG region, and salidroside intervention inhibited the
process of cell apoptosis. The expressions of RhoA, p-ERK, p-JNK decreased after
hypobaric hypoxia exposure. Salidroside intervention reversed RhoA expression and
raised the levels of p-ERK and p-JNK. CONCLUSION: Acute exposure to hypobaric
hypoxia can induce cell apoptosis in rat hippocampal DG, and salidroside can
protect the cells from the exposure-induced apoptosis.
PMID- 26429533
TI - [The changes of Wnt7b/beta-catenin signaling pathway molecules in the
differentiation of fetal alveolar epithelial type II cells].
AB - OBJECTIVE: To investigate the changes of Wnt7b/beta-catenin signaling pathway
molecules in the differentiation of fetal rat alveolar epithelial type II cells
(fAEC2). METHODS: Fetal rat lung tissues were extracted from pregnant SD rats (19
days), and then fAEC2 were isolated and purified. After fAEC2 were cultured for
48, 72, 96 hours, the morphological changes of fAEC2 and the expression of beta
catenin were respectively observed by inverted microscope and immunofluorescence.
The mRNA expressions of Wnt7b, cyclin D1, pulmonary surfactant C (SP-C) and
aquaporin 5 (AQP5) were detected by real-time quantitative PCR. The protein
expressions of cyclin D1, nucleus beta-catenin, SP-C and AQP5 were measured by
Western blotting. RESULTS: beta-catenin was expressed in cell membrane when fAEC2
were cultured for 48 hours; the expression of beta-catenin decreased in cell
membrane while enhanced in cytoplasm and nucleus at 72 hours; whole-cell beta
catenin expression was lowered at 96 hours. The expressions of Wnt7b and cyclin
D1 mRNAs were significantly raised at 72 hours and reduced obviously at 96 hours
compared with 48 hours. SP-C mRNA expression level went down gradually with the
extended culture time, and AQP5 mRNA level went up gradually. The protein
expressions of cyclin D1 and nucleus beta-catenin were significantly enhanced at
72 hours and weakened at 96 hours compared with 48 hours. SP-C protein expression
was down-regulated with the prolonged culture time, and AQP5 protein expression
was up-regulated. CONCLUSION: Wnt7b/beta-catenin signaling pathway may play an
important role in fAEC2 transdifferentiation.
PMID- 26429534
TI - [Roles of Toll-like receptor 2 (TLR2) and TLR4 in immune responses to Chlamydia
trachomatis genital tract infection in mice].
AB - OBJECTIVE: To evaluate the roles of Toll-like receptor 2 (TLR2) and TLR4 in
immune responses to Chlamydia trachomatis (Ct) genital tract infection in mice.
METHODS: The wild type (WT, n=11), TLR2(-/-) (n=14) and TLR4(-/-) (n=11) mice
were inoculated intravaginally with 1*10(4) inclusion forming units (IFUs) of
live C.muridarum (strain MoPn/Nigg) to establish the models of Ct genital tract
infection. The vaginal swabs were taken at the 3rd, 7th, 10th, 17th, 24th, 31st,
38th, 45th day after the infection. Immunofluorescence assay was used to quantify
live organisms from each swab. The inflammatory cytokines interleukin-1alpha (IL
1alpha), IL-6 and macrophage inflammatory protein 2 (MIP-2) were measured using
ELISA. The 70th day post infection, the titers of mouse serum Ct-specific
antibody isotypes were determined using an immunofluorescence technique; after
the macrophages harvested from peritoneal cavity were infected with MoPn strain
for 24 hours, the culture supernatants were examined for the contents of
cytokines IL-1alpha, IL-6 and MIP-2 using ELISA. The harvested splenocytes were
stimulated with UV-inactivated chlamydial antigens for 72 hours, and the culture
supernatants were measured for the levels of cytokines interferon gamma (IFN
gamma), IL-17, IL-4 and IL-5 using ELISA. RESULTS: No significant difference was
observed in the number of IFUs from the vaginal swabs at any time points post
infection among WT, TLR2(-/-) and TLR4(-/-) mice. All mice displayed similar time
course of live organism shedding. Until the 38th day, all mice cleared live
organism. Macrophages lacking TLR2 produced significantly decreased amounts of IL
1alpha, IL-6 and MIP-2 compared with those in WT mice; however, there was no
significant difference between WT and TLR4(-/-) mice. The vaginal swab samples
from TLR2(-/-) mice also had lower levels of inflammatory cytokines. Splenocytes
from the three groups of mice all produced high levels of both IFN-gamma and IL
17, and low levels of both IL-4 and IL-5, and no significant difference was found
among the three groups. The ratio of serum IgG2a/IgG1 in the three groups of mice
was greater than 1, and no significant difference was found among the three
groups. CONCLUSION: TLR2, rather than TLR4 mediates early immune response
following Ct genital tract infection in mice. However, neither TLR4 nor TLR2 is
required for adaptive immune responses induced by Ct genital tract infection.
PMID- 26429535
TI - [Effects of subunit influenza vaccines in a mouse model of asthma].
AB - OBJECTIVE: To explore the effects of subunit influenza vaccines on mouse model of
asthma. METHODS: Six-week-old female BALB/c mice were randomly divided into PBS
control group, asthma control group and subunit influenza vaccine group. Mice in
the asthma control group and the subunit influenza vaccine group were sensitized
on the 0, 7th, 14th day by intraperitoneal injection of 50 MUg ovalbumin (OVA)
emulsified in 2 mg aluminum hydroxide. The PBS control animals were given an
equal volume of PBS. The mice in the subunit influenza vaccine group were
immunized intramuscularly with 0.1 mL subunit influenza vaccines on the 21st day,
and were boosted intranasally with 40 MUL vaccines on the 28th day. Subsequently,
the mice in the asthma control group and the subunit influenza vaccine group were
exposed to OVA aerosol challenge for 3 consecutive days (the 42nd, 43rd, 44th
day). Within 48 hours after the last challenge, all mice were sacrificed after
the blood was obtained, and the bronchoalveolar lavage fluid (BALF) samples were
collected for cell counting and classification. Lung tissues were prepared and HE
staining and PAS staining were used to evaluate pulmonary inflammation and mucus
production. IgE levels in sera and interleukine 4 (IL-4), IL-5, IL-13, interferon
gamma (IFN-gamma) levels in BALF were measured by ELISA. RESULTS: Compared with
the PBS control group, the pulmonary inflammation and mucus production
significantly increased in the asthma control group and the subunit influenza
vaccine group, and the levels of IL-4, IL-5, IL-13, IFN-gamma in BALF and serum
IgE were also significantly elevated. However, no significant difference was
found between the subunit influenza vaccine group and the asthma control group.
CONCLUSION: In mouse model of asthma, the use of subunit influenza vaccine does
not exacerbate asthma symptoms, and is relatively safe.
PMID- 26429536
TI - [Rich selenium-Banqiao-Codonopsis Pilosula mixture enhances immune function of
aging mice].
AB - OBJECTIVE: To investigate the effect of rich selenium-Banqiao-Codonopsis Pilosula
(RSBCP) mixture on the immune functions of the aging mice. METHODS: Sixty Kunming
mice (half male and half female) were randomly divided into high-, middle- and
low-dose RSBCP mixture groups, model group and control group, with twelve mice in
each group. The control group was injected intraperitoneally with 500 mg/(kg.d)
normal saline and the other groups were injected with the same amount of D
galactose. The RSBCP mixture high-, middle- and low-dose groups were respectively
gavaged with 100, 50, 25 g/(kg.d) RSBCP mixture at the moment when D-galactose
was injected. The model group and control group were given the same amount of
distilled water instead. The mice were killed at the 30th days and the indexes of
thymus and spleen were measured. The serum levels of IgG, IgM, C3, C4,
interleukine 2 (IL-2), IL-6 and tumor necrosis factor alpha (TNF-alpha) were
detected by ELISA and the major T-cell subsets of splenocytes were analyzed by
flow cytometry. RESULTS: Compared with the control group, the indexes of thymus
and spleen in the model group decreased obviously; the serum levels of IgG, IgM,
C3, C4, IL-2 and IL-6 were reduced significantly and the level of TNF-alpha
increased significantly. Compared with the model group, the indexes of thymus and
spleen in the RSBCP mixture groups increased obviously; the levels of IgG, IgM,
C3, C4, IL-2 and IL-6 were raised significantly and the level of TNF-alpha
decreased significantly. Compared with the control group, the indexes of thymus
and spleen in the RSBCP mixture high-dose group increased obviously; the levels
of IgG, IgM, C3, C4, IL-2 and IL-6 were lifted significantly and the level of TNF
alpha decreased significantly. The indexes of thymus and spleen and the levels of
IgG, IgM, C3, C4, IL-2 and IL-6 in the RSBCP mixture middle- and low-dose groups
had no obvious differences from those of the control group. Compared with the
control group, the model group showed significantly decreased numbers of CD3+ T,
CD4+ T, CD44+ T cells and significantly increased number of CD8+ T cells.
Compared with the model group, the RSBCP mixture groups showed significantly
increased numbers of CD3+ T, CD4+ T, both the high- and middle-dose groups showed
significantly increased numbers of CD44+ T cells and significantly decreased
number of CD8+ T cells. CONCLUSION: RSBCP mixture could delay the atrophy of
thymus and spleen in the aging mice, dramatically elevate serum levels of IgG,
IgM, C3, C4, IL-2, IL-6, lower the level of TNF-alpha, and influence the
proportions of T cell subsets. The mixture plays a role in enhancing the immune
function of aging mice.
PMID- 26429537
TI - [Total saponins of Chaenomeles speciosa inhibit the degranulation of primary
mouse bone marrow-derived mast cells in vitro].
AB - OBJECTIVE: To study the effects of total saponins of Chaenomeles speciosa on the
degranulation of mouse bone marrow-derived mast cells (BMMCs). METHODS: Bone
marrow cells were isolated from C57BL/6 mice and were cultured in RPMI1640 medium
containing 100 mL/L fetal bovine serum, 20 ng/mL IL-3 and 40 ng/mL stem cell
factor (SCF). After four-week culture, flow cytometry was used to identify the
purity of double-positive (CD117(+)FcEpsilonRIalpha(+)) mast cells; toluidine
blue was used to detect the maturity of mast cells. After total saponins of
Chaenomeles speciosa was added into the medium of BMMCs, CCK-8 assay was
performed to assess the toxic effects of total saponins of Chaenomeles speciosa
on BMMCs; the amount of beta-hexosaminidase release was detected by fluorescence
spectrophotometry; the content of tryptase in cell supernatants was detected by
ELISA. RESULTS: After cultured for four weeks, the purity of double-positive
cells was more than 95%, and the cells presented the features of mature mast
cells, with blue nuclear and purple cytoplasm by toluidine blue staining. After
BMMCs were cultured in the presence of total saponins of Chaenomeles speciosa
(0.01, 0.03, 0.10 mg/mL) for 12 hours, CCK-8 assay indicated that the total
saponins did not exert the toxic effects on the BMMCs. Fluorescence
spectrophotometry revealed that the release amount and release rate of beta
hexosaminidase decreased in the cells treated with the total saponins of
Chaenomeles speciosa, DNP-BSA and A23187 compared with the controls, and ELISA
assay showed that the amount of tryptase release in the supernatants was reduced
as well. CONCLUSION: Total saponins of Chaenomeles speciosa can inhibit the
degranulation of primary mouse BMMCs stimulated by different antigens with a
clear dose-effect relationship.
PMID- 26429538
TI - [Effects of different processing methods and durations of blood specimens on the
level of soluble CD100 in peripheral blood].
AB - OBJECTIVE: To investigate the effects of different processing methods and
durations of blood specimens on the level of soluble CD100 (sCD100) in peripheral
blood. METHODS: We included a total of 15 healthy individuals without any
significant signs or symptoms of microbial infection. Blood samples were
collected in tubes with and without additives, as well as tubes containing
citrate, EDTA and heparin, respectively, and processed for different durations of
time. The serum samples were allowed to clot for 1 hour, 4, 8 hours after
venipuncture before centrifugation. Then the sCD100 levels were measured with
ELISA. RESULTS: Serum sCD100 levels were higher than those in plasma, and no
significant differences were observed among the citrate, EDTA or heparin treated
plasma groups. The sera in the tubes without additives showed lower levels of
sCD100 than those in the tubes with additives. The concentrations of sCD100 in
sera increased with the prolonged processing time in room temperature.
CONCLUSION: The measurement of sCD100 in blood samples may be interfered by the
in vitro release from platelets. Thus, pre-treating methods for the collection of
serum or plasma samples are critical in the assessment of sCD100 concentrations
and should be carefully considered for the measurement of this important
biomarker in both basic and clinical studies.
PMID- 26429539
TI - [Up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) of CD4+ T
cells is positively related to RORC and IL-17A in patients with Kawasaki
disease].
AB - OBJECTIVE: To investigate the expression of serum- and glucocorticoid-inducible
kinase 1 (SGK1) in Kawasaki disease (KD) and explore the correlations between
SGK1 and Th17 cell-related cytokines [retinoic-acid-related orphan nuclear
receptor C (RORC), interleukin 17A (IL-17A), IL-6] in KD. METHODS: Thirty
patients with KD [(2.8 +/- 1.4) years old], 30 healthy volunteers [(2.6 +/- 1.6)
years old] and 25 patients with infectious disease (ID) [(2.2 +/- 1.5) years old]
were recruited. The percentage of Th17 cells in CD4+ T cells was analyzed using
flow cytometry. The mRNA levels of RORC and SGK1 in CD4+ T cells were detected
using real-time quantitative PCR. The serum levels of IL-17A and IL-6 were
analyzed by ELISA. RESULTS: Compared with healthy volunteers and patients with
ID, the percentage of Th17 cells in CD4+ T cells significantly increased in KD
[(3.57 +/- 0.62)% vs (0.51 +/- 0.07)% or (1.72 +/- 0.36)%]. The serum levels of
IL-17A and IL-6 in KD were much higher than those in healthy volunteers and
patients with ID. The mRNA levels of RORC and SGK1 in KD were remarkably elevated
compared with healthy volunteers and patients with ID. The level of SGK1 in
coronary artery lesion (CAL) group of KD was significantly higher than that in KD
patients with normal coronary artery (CAN). SGK1 was reduced in KD after
intravenous immunoglobulin (IVIG) treatment. What's more, the decrease of SGK1
was more obviously in the CAL group than in the CAN group. In addition, SGK1
expression in KD was positively correlated with RORC and IL-17A, but not with IL
6. CONCLUSION: SGK1 was up-regulated in CD4+ T cells and was positively
correlated with RORC and IL-17A in the patients with KD.
PMID- 26429540
TI - [The differentiation and clinical significance of follicular helper T cells
during acute exacerbation in asthma patients].
AB - OBJECTIVE: To observe the differentiation of follicular helper T (Tfh) cells in
asthma patients during acute exacerbation and post-treatment periods, and explore
the clinical significance of Tfh cells in asthma. METHODS: We detected the
percentages of CD4+CXCR5+, CD4+ICOS+, CD4+CXCR5+ICOS+ T cells in peripheral blood
mononuclear cells (PBMCs) by flow cytometry, the level of Bcl-6 mRNA in CD4+ T
cells by reverse transcription PCR, and the level of interleukin 21 (IL-21) in
plasma by ELISA in healthy controls and asthma patients during acute exacerbation
and post-treatment release periods. The linear regression analysis was used to
analyze the correlations of the level of IL-21 in plasma with forced expiratory
volume in one second/forced vital capacity (FEV1/FVC) and forced expiratory
volume in one second/prediction (FEV1/Pre) in acute exacerbation period of asthma
patients. RESULTS: The percentages of CD4+CXCR5+, CD4+CXCR5+ICOS+ T cells in
PBMCs, the level of Bcl-6 mRNA in CD4+T cells, and the level of IL-21 in plasma
increased in acute exacerbation of the asthma patients compared to the healthy
controls. After treatment, the percentages of CD4+CXCR5+, CD4+ICOS+,
CD4+CXCR5+ICOS+ T cells in PBMCs, the level of Bcl-6 mRNA in CD4+T cells, and the
level of IL-21 in plasma in asthma patients were all reduced as compared with the
acute exacerbation period. There were negative correlations between IL-21 and
lung function parameters such as FEV1/FVC and FEV1/Pre. CONCLUSION: The
differentiation of Tfh cells was enhanced in acute exacerbation of asthma
patients, and ameliorated after treatment. Tfh cells may participate in the
inflammatory reaction of asthma, and the differentiation degree of Tfh cells may
reflect the extent of airway limitation in asthma patients.
PMID- 26429541
TI - [The frequency of peripheral blood CD14(+)HLA-DR(-/low) MDSCs is negatively
correlated with the inflammation in patients with chronic hepatitis B].
AB - OBJECTIVE: To study the frequency of CD14+HLA-DR(-/low) myeloid-derived
suppressor cells (MDSCs) in the peripheral blood of chronic hepatitis B (CHB)
patients and the relationship with biochemical characteristics, viral load and
liver pathology. METHODS: The frequency of CD14+HLA-DR(-/low) MDSCs in the
peripheral blood of 96 patients with CHB and 20 healthy control cases were
detected by flow cytometry. Ultrasound-guided liver biopsies as well as HBV
related serological tests were performed in HBV-infected individuals to analyze
the biochemical characteristics, viral load and pathology. The data were assessed
using Spearman correlation analysis. RESULTS: The frequency of the peripheral
blood CD14+HLA-DR(-/low) MDSCs in the 96 CHB cases was (6.03 +/- 0.09)%, which
was significantly higher than that of the 20 healthy control cases (1.87 +/-
0.05)%. The group of HBeAg positive cases had a significantly higher frequency of
the peripheral blood CD14+HLA-DR(-/low) MDSCs compared with the group of HBeAg
negative cases and the healthy control group. The frequency of CD14+HLA-DR(-/low)
MDSCs in the peripheral blood was negatively correlated with serum alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) levels. There was no
correlation between the frequency of peripheral blood CD14+HLA-DR(-/low) MDSCs
and HBV load. The frequency of CD14+HLA-DR(-/low) MDSCs in the peripheral blood
was negatively correlated with the liver inflammation grade, but not related with
the fibrosis stage in patients with CHB. CONCLUSION: The frequency of CD14+HLA
DR(-/low) MDSCs is negatively correlated with the inflammation of CHB.
PMID- 26429543
TI - [Development and characterization of polyclonal antibody against regeneration
(rgn) of Drosophila].
AB - OBJECTIVE: To prepare and characterize rat polyclonal antibodies highly specific
for Drosophila regeneration (rgn). METHODS: Gene fragments rgn were cloned from
Drosophila W(1118) cDNAs by PCR and then subcloned into vector pRSETA. Its
expression was induced in E.coli JM109(DE3). Then the fusion protein was purified
by Ni-NTA superflow chromatography. After the products was identified by Western
blotting, SD male rats were immunized with the rgn fusion protein. The polyclonal
antibodies were obtained from the rat serum. The specificity and titer of the
polyclonal antibodies were detected by Western blotting and immunohistochemistry.
RESULTS: Through the recombinant plasmid pRSETA-rgn, 6*His-rgn fusion protein was
expressed abundantly in E.coli JM109(DE3). After purification, it was used to
immunize SD rats as antigen to generate the polyclonal antibodies against rgn.
Immunohistochemistry showed that rgn is located in the cytoplasm of hemocytes of
the third instar larvae of Drosophila. CONCLUSION: The experiment has prepared
high-specificity rat polyclonal antibodies against rgn.
PMID- 26429542
TI - [Cytomegalovirus infection down-regulates the expressions of CD226 and CD16 in
blood NK cells of the renal transplant recipient].
AB - OBJECTIVE: To investigate the effect of cytomegalovirus (CMV) infection after
renal transplantation on the expressions of the activation receptors CD226 and
sCD16 in natural killer (NK) cells. METHODS: Peripheral blood samples were
obtained from these kidney transplant recipients with CMV infection, stable
recipients, and normal healthy controls, and the expressions of CD3, CD56, CD16
and CD226 of all the samples were analyzed by flow cytometry. RESULTS: Compared
with patients recovered from CMV infection, normal healthy controls and the
stable recipients, the percentage of NK population in lymphocytes did not vary
among these groups (P=0.18). However, the percentage of peripheral blood CD226+NK
cells in NK population of the CMV infection group [(75.06 +/- 13.65)%] was
significantly lower than that of the healthy controls [(88.28 +/- 11.98)%] and
stable recipients [(87.53+/-6.43)%]. While the percentage was recovered during
CMV infection recovery stage [(88.37+/-8.91)%], which was not different from that
of normal healthy controls and the stable recipients. The mean fluorescence
intensity (MFI) of CD226 was not significantly different among the health
controls, stable recipients and CMV infection patients, while it was
significantly higher in the patients recovered from CMV infection than in the
above three groups. A decrease in the percentage of CD16(+)NK cells in NK
population was observed in the group of CMV infection [(75.06 +/- 13.65)%], which
was significantly lower than that of the stable recipients [(88.28 +/- 11.98)%]
and health controls [(90.35 +/- 10.07)%]. The CD16 expression on NK cells was
elevated to (86.30 +/- 14.01)% when the infection was controlled, which was not
different from the stable recipients and healthy controls. The MFI of CD16MFI in
NK cells was similar in all groups. CONCLUSION: CMV infection down-regulates the
expressions of CD226 and CD16 in NK cells of patients after kidney
transplantation. When the infection was controlled, the expressions of CD226 and
CD16 on NK cells were recovered. These results indicated that the membrane CD226
and CD16 molecules were involved in NK cell-mediated anti-CMV infection.
PMID- 26429544
TI - [Single chain antibody against beta-site of amyloid precursor protein inhibits
the generation of beta-amyloid peptide].
AB - OBJECTIVE: To construct and express a single chain fragment of variety region
(scFv) against beta-site of amyloid precursor protein (APP), and evaluate the
effect of scFv on alpha- and beta-processing of APP. METHODS: The beta-site
specific scFv 2H10 was amplified and fused with signal sequence Igkappa and myc
tag by PCR to create the expression cassette, which was then subcloned into
expression vector pcDNA3.1hyg+. The plasmid was transferred into CHO cells over
expressing Swedish mutation type human APP695 (APP695sw/CHO). The positive clones
were identified by hygromycin B. The concentrations of Abeta40 and soluble
APPalpha (sAPPalpha) in the conditioned media supernatant were measured by
sandwich ELISA. RESULTS: The recombinant eukaryotic expression plasmids were
identified by PCR, restriction endonuclease digestion and DNA sequencing. The
expression of scFv was confirmed by Western blotting. When scFv 2H10 was stably
expressed in APP695sw/CHO, the extracellular level of Abeta40 decreased by 30.4%,
while sAPPalpha increased by 23.1%. CONCLUSION: The APP beta-site scFv 2H10 could
inhibit the secretion of Abeta. Meanwhile, it might be favorable for the alpha
processing of APP. Hence it can be explored as an inhibitor of beta-site APP
cleaving enzyme (BACE).
PMID- 26429545
TI - Does the EU migration level of chromium VI in toys need to be lowered?
PMID- 26429546
TI - Connectivity, contest and the ties of self-management support for type 2
diabetes: a meta-synthesis of qualitative literature.
AB - This paper presents a meta-synthesis of the literature on community-based self
management to support experiences of people diagnosed with type 2 diabetes. The
aim was to synthesise findings on both formal and informal self-management
support with particular reference to the relevance and influence of the social
context operating at different levels. The review forms part of EU-WISE, a
project financed through EU's 7th Framework Programme. The review was performed
by systematically searching MEDLINE, PubMed, EMBASE, CINAHL, PsycINFO and Web of
Science for English language publications between 2005 and 2014 presenting
research conducted in Europe on the experiences and perspectives of self
management concerns of patients diagnosed with type 2 diabetes. The search
yielded 587 abstracts, which were reduced through search strategy refinement and
eligibility and quality criteria to 29 papers that were included in the review.
This review highlights the relevance of contextual factors operating at micro-
and macro-levels. The synthesis yielded six second-order thematic constructs
relating to self-management: sense of agency and identity, the significance and
meaning of social networks, minimal disruption of everyday life, economic
hardship, the problem of assigning patients' responsibility and structural
influences of primary care. Using a line of argument synthesis, these themes were
revisited, and a third-order construct, connectivity emerged which refers to how
links in daily life are interwoven with peoples' social networks, local
communities, economic and ideological conditions in society in a way which
support self-management activities. This meta-synthesis indicates a need to heed
the notion of connectivity as a means of mobilising and supporting the self
management strategies of people with type 2 diabetes in everyday life.
PMID- 26429548
TI - Outcomes of Bone Grafting of Bone Cysts After Total Ankle Arthroplasty.
AB - BACKGROUND: The operative treatment of bone cysts after total ankle replacements
(TAR) is not well described. Bone cysts may cause component migration, implant
failure, and pain. Surgery is performed on cysts with the goals of reducing pain
and preventing component failure. METHODS: We retrospectively evaluated a
consecutive series of 726 primary TARs performed between January 1998 and May
2013 and identified those who had a subsequent bone cyst grafting procedure. We
identified cyst location and method of treatment. Clinical outcomes including
secondary procedures, infection rate, complications, and failure rate were
recorded. Thirty-one patients were treated with a total of 33 operative
procedures for bone cysts after TAR. Of these patients, 22 (71.0%) were males
with an average age of 62.2 and median follow-up 65.9 months. RESULTS:
Intraoperatively, 22 tibial cysts (71.0%), 20 talar cysts (64.5%), 5 fibular
cysts (16.1%), and 13 multiple cysts (41.9%) were treated. Allograft was used in
25 procedures (75.8%), calcium phosphate in 4 (12.1%), cement in 3 (9.1%), and
autograft in 1 (3.0%). These procedures were supplemented by calcaneus autograft,
allograft mixed with mesenchymal stem cells, platelet-rich plasma, recombinant
human bone morphogenic protein-2, and demineralized bone matrix. There were no
infections or wound complications. Of the 27 subjects with a successful second
surgery, the success rate for bone grafting of cysts was 90.9% (95% CI: 50.8,
98.7%) at 24 months and 60.6% (95% CI: 25.1%, 83.4%) at 48 months. One patient
needed a repeat bone grafting. The 4 failures observed postprocedure resulted in
3 tibial and talar component revisions, and 1 tibiotalocalcaneal (TTC) fusion.
CONCLUSIONS: Grafting bone cysts without revision of TAR was in general an
effective and safe means for treating patients with peri-prosthetic bone cysts.
Treatment with grafting and supplemental materials may improve implant
survivorship and might improve the structural support surrounding the implant.
Further exploration of the etiology of bone cysts may aid in the prevention and
treatment of cystic formation in the TAR. LEVEL OF EVIDENCE: Level IV, case
series.
PMID- 26429547
TI - Impact of flanking chromosomal sequences on localization and silencing by the
human non-coding RNA XIST.
AB - BACKGROUND: X-chromosome inactivation is a striking example of epigenetic
silencing in which expression of the long non-coding RNA XIST initiates the
heterochromatinization and silencing of one of the pair of X chromosomes in
mammalian females. To understand how the RNA can establish silencing across
millions of basepairs of DNA we have modelled the process by inducing expression
of XIST from nine different locations in human HT1080 cells. RESULTS:
Localization of XIST, depletion of Cot-1 RNA, perinuclear localization, and
ubiquitination of H2A occurs at all sites examined, while recruitment of H3K9me3
was not observed. Recruitment of the heterochromatic features SMCHD1, macroH2A,
H3K27me3, and H4K20me1 occurs independently of each other in an integration site
dependent manner. Silencing of flanking reporter genes occurs at all sites, but
the spread of silencing to flanking endogenous human genes is variable in extent
of silencing as well as extent of spread, with silencing able to skip regions.
The spread of H3K27me3 and loss of H3K27ac correlates with the pre-existing
levels of the modifications, and overall the extent of silencing correlates with
the ability to recruit additional heterochromatic features. CONCLUSIONS: The non
coding RNA XIST functions as a cis-acting silencer when expressed from nine
different locations throughout the genome. A hierarchy among the features of
heterochromatin reveals the importance of interaction with the local chromatin
neighborhood for optimal spread of silencing, as well as the independent yet
cooperative nature of the establishment of heterochromatin by the non-coding XIST
RNA.
PMID- 26429549
TI - Vitamin D Status in an Elective Orthopedic Surgical Population.
AB - BACKGROUND: Adequate vitamin D availability is required for normal bone
metabolism. Hypovitaminosis D is highly prevalent in latitudes above 30 degrees.
The goal of this prospective study was to determine the prevalence of
hypovitaminosis D in an unselected population of patients undergoing major ankle
or hindfoot arthrodesis in Burlington, Vermont (latitude 44.5 degrees N).
METHODS: One hundred eighteen patients undergoing a major ankle, hindfoot, or
midfoot arthrodesis between May 2012 and February 2014 were eligible for the
study, of which 81 participated. All clinical data, including comorbidities,
demographics, and lab values, were obtained from the comprehensive electronic
medical record system that encompassed all inpatient and outpatient care. Based
on the recommendations published by the Vitamin D Task Force Committee of the
Endocrine Society, vitamin D levels above 30 ng/mL were considered normal.
Statistical analyses were performed using a significance level of P <.05.
RESULTS: Of 81 patients tested, 54 (67%) had low serum vitamin D. Older patients
had lower risk for hypovitaminosis D (RR = 0.953, CI = 0.908, 0.999, P = .046),
whereas a Charlson Index >=3 had increased risk (RR = 16.8, CI = 1.5, 192.3, P =
.023). Of the 16 patients retested after vitamin supplementation, only 9 (56%)
corrected to normal. CONCLUSIONS: In an unselected population in Vermont
undergoing hindfoot and ankle arthrodesis, there was a high prevalence of
hypovitaminosis D, even in patients without predisposing risk factors.
Consequently, routine testing or presumptive high-dose vitamin D replenishment
therapy should be considered for all patients scheduled for such surgery,
primarily to promote adequate skeletal calcium metabolism. LEVEL OF EVIDENCE:
Level II, prospective study.
PMID- 26429550
TI - Culture and molecular identification of fungal contaminants in edible bird nests.
AB - Widespread food poisoning due to microbial contamination has been a major concern
for the food industry, consumers and governing authorities. This study is
designed to determine the levels of fungal contamination in edible bird nests
(EBNs) using culture and molecular techniques. Raw EBNs were collected from five
house farms, and commercial EBNs were purchased from five Chinese traditional
medicine shops (companies A-E) in Peninsular Malaysia. The fungal contents in the
raw and commercial EBNs, and boiled and unboiled EBNs were determined. Culturable
fungi were isolated and identified. In this study, the use of these methods
revealed that all EBNs had fungal colony-forming units (CFUs) that exceeded the
limit set by Standards and Industrial Research Institute of Malaysia (SIRIM) for
yeast and moulds in EBNs. There was a significant difference (p < 0.05) in the
number of types of fungi isolated from raw and commercial EBNs, but no
significant difference in the reduction of the number of types of fungi after
boiling the EBNs (p > 0.05). The types of fungi isolated from the unboiled raw
EBNs were mainly soil, plant and environmental fungi, while the types of fungi
isolated from the boiled raw EBNs, unboiled and boiled commercial EBNs were
mainly environmental fungi. Aspergillus sp., Candida sp., Cladosporium sp.,
Neurospora sp. and Penicillum sp. were the most common fungi isolated from the
unboiled and boiled raw and commercial EBNs. Some of these fungi are mycotoxin
producers and cause opportunistic infections in humans. Further studies to
determine the mycotoxin levels and methods to prevent or remove these
contaminations from EBNs for safe consumption are necessary. The establishment
and implementation of stringent regulations for the standards of EBNs should be
regularly updated and monitored to improve the quality of the EBNs and consumer
safety.
PMID- 26429551
TI - Astaxanthin Protecting Membrane Integrity against Photosensitized Oxidation
through Synergism with Other Carotenoids.
AB - Incorporation of astaxanthin or zeaxanthin in giant unilamellar vesicles (GUVs)
of phosphatidylcholine resulted in a longer lag phase than incorporation of beta
carotene or lycopene for the onset of budding induced by chlorophyll a
photosensitization and quantified by a dimensionless entropy parameter using
optical microscopy and digital image heterogeneity analysis. The lowest initial
rate of GUV budding after the lag phase was seen for GUVs with astaxanthin as the
least reducing carotenoid, while the lowest final level of entropy appeared for
those with lycopene or beta-carotene as a more reducing carotenoid. The
combination of astaxanthin and lycopene gave optimal protection against budding
with respect to both a longer lag phase and lower final level of entropy by
combining good electron acceptance and good electron donation. Quenching of
singlet oxygen by carotenoids close to chlorophyll a in the membrane interior in
parallel with scavenging of superoxide radicals by astaxanthin anchored in the
surface may explain the synergism between carotenoids involving both type I and
type II photosensitization by chlorophyll a.
PMID- 26429552
TI - Temperatures of storage areas in large animal veterinary practice vehicles in the
summer and comparison with drug manufacturers' storage recommendations.
AB - BACKGROUND: Large animal veterinarians carry drugs in their practice vehicles in
storage areas that are not typically refrigerated. The most common upper limits
of manufacturers' storage temperatures for United States (U.S.)-approved non
refrigerated drugs are 25 or 30 degrees C. Because ambient temperatures in many
locations in the U.S. exceed these temperatures during the summer, we measured
storage area temperatures over 4 months in the summer of 2013 to evaluate the
extent to which labeled storage temperatures are exceeded. METHODS: A convenience
sample of 12 vehicles from 5 central Texas practices and 12 vehicles from 4 south
central Nebraska practices was used. Temperatures were recorded in one drug
storage compartment in each vehicle from May 15 - September 16, 2013, at 15
minute intervals using a self-contained, battery operated temperature recording
device. RESULTS: The highest temperatures recorded in a storage unit were 54.4
and 47.7 degrees C in Texas and Nebraska, respectively. The mean temperature
recorded across all 24 storage units was 29.1 degrees C, with a mean of 26.9
degrees C in Nebraska and 31.4 degrees C in Texas. In Nebraska, at least one
temperature over 25 degrees C was recorded on a mean of 111/124 days and a mean
of 63 % of total logger readings. In Texas, temperatures over 25 degrees C were
recorded on a mean of 123/124 days and a mean of 95 % of total logger readings.
CONCLUSIONS: Temperatures in storage units in participating veterinary practice
vehicles exceeded labeled drug storage temperatures a significant portion of the
summer of 2013. More research is needed to determine whether these excursions
above the manufacturers' recommended storage temperatures alter efficacy of
stored drugs.
PMID- 26429553
TI - Multiple fractures in a 22-year-old man after a simple fall.
AB - We present the case of a 22-year-old male with longstanding progressive fatigue,
weakness and pain around his hips due to an undiagnosed parathyroid adenoma. The
resultant primary hyperparathyroidism ultimately caused pathologic fractures. He
was admitted to the hospital for further assessment and excision of the
parathyroid adenoma. A few days after admission, he fell down while walking and
was referred to our team. X-rays showed a displaced left femoral neck fracture
(FNF) and right humeral shaft fracture with poor bone quality. His humeral
fracture was treated conservatively, and the FNF was treated with total hip
replacement. Three days later, he underwent parathyroidectomy. This case
demonstrates the importance of a thorough investigation of progressive weakness
even in a young individual and illustrates the importance of early diagnosis of
parathyroid adenoma to avoid the devastating end results of this condition.
PMID- 26429554
TI - Postcoital hemoperitoneum caused by ruptured corpus luteal cyst: a hidden
etiology.
AB - Corpus luteal rupture is a common gynecologic cause for hemoperitoneum. Recent
sexual intercourse is usually a preceding factor. However, postcoital
hemoperitoneum without evident vaginal injury or trauma is rarely reported. We
present a 34-year-old female who presented to the emergency department with
severe bilateral lower quadrant abdominal pain after sexual intercourse. CT of
the abdomen and pelvis revealed an intra-abdominal hematoma with extravasation of
contrast questionable to be from one of the branches of the left internal iliac
artery, and no adnexal abnormalities. Left internal iliac artery angiogram was
performed and revealed no active extravasation. Exploratory laparotomy was
performed and revealed an actively bleeding left ovarian ruptured area that was
repaired and biopsied. No evidence of cysts was observed. Histopathological
examination revealed a hemorrhagic corpus luteal cyst. Suspicion for corpus
luteal rupture as a cause of postcoital hemoperitoneum should be maintained
despite nonevidence of cysts on CT or intraoperatively.
PMID- 26429555
TI - Heterotopic ossification in chronic fibrosing otitis externa.
AB - Acquired external auditory canal atresia is a rare complication of chronic
inflammatory otitis, and is generally fibrous or soft tissue in nature. Here, we
present the first reported case of heterotopic ossification within chronic
fibrosing otitis externa in a 25-year-old male patient with a childhood history
of granular myringitis and failed tympanoplasty. A calcified mass was
demonstrated adjacent to the tympanic membrane on CT imaging, and surgical
exploration revealed a cohesive bar of bone traversing the medial external
auditory canal. Drill canaloplasty and split-thickness skin graft coverage of the
lateral tympanic membrane resulted in an improvement in the pure tone average
from 79 to 55 dB. As the treatment for chronic fibrosing otitis externa involves
the surgical widening of the external auditory canal, we alert surgeons to the
possibility of cohesive bone formation as a potential cause of navigational
confusion and inadvertent over- or under-drilling of the canal stenosis.
PMID- 26429556
TI - Monoamine Oxidase Inhibitory Action of Chalcones: A Mini Review.
AB - INTRODUCTION: Chalcones are one of the major classes of naturally occurring
compounds and have a vast significance in medicinal chemistry, presenting with a
wide scope of pharmacological actions. DISCUSSION: The present review focused our
attention onto the monoamine oxidase inhibitory activity of natural and synthetic
chalcones. The review also emphasises the structure-activity relationship studies
and molecular recognition of chalcones towards MAO-A and B inhibition.
CONCLUSION: Many of the studies clearly revealed that most of the chalcones
showed selective, reversible and potent MAO-B inhibition compared to MAO-A.
Recent studies also showed that heteroaryl-based chalcones are potent MAO-A
inhibitors.
PMID- 26429557
TI - Fully Automated Sample Preparation for Ultrafast N-Glycosylation Analysis of
Antibody Therapeutics.
AB - There is a growing demand in the biopharmaceutical industry for high-throughput,
large-scale N-glycosylation profiling of therapeutic antibodies in all phases of
product development, but especially during clone selection when hundreds of
samples should be analyzed in a short period of time to assure their
glycosylation-based biological activity. Our group has recently developed a
magnetic bead-based protocol for N-glycosylation analysis of glycoproteins to
alleviate the hard-to-automate centrifugation and vacuum-centrifugation steps of
the currently used protocols. Glycan release, fluorophore labeling, and cleanup
were all optimized, resulting in a <4 h magnetic bead-based process with
excellent yield and good repeatability. This article demonstrates the next level
of this work by automating all steps of the optimized magnetic bead-based
protocol from endoglycosidase digestion, through fluorophore labeling and cleanup
with high-throughput sample processing in 96-well plate format, using an
automated laboratory workstation. Capillary electrophoresis analysis of the
fluorophore-labeled glycans was also optimized for rapid (<3 min) separation to
accommodate the high-throughput processing of the automated sample preparation
workflow. Ultrafast N-glycosylation analyses of several commercially relevant
antibody therapeutics are also shown and compared to their biosimilar
counterparts, addressing the biological significance of the differences.
PMID- 26429558
TI - An Empirical Comparison of Competing Factor Structures for the Repeatable Battery
for the Assessment of Neuropsychological Status: A Project FRONTIER Study.
AB - The original factor structure of the Repeatable Battery for the Assessment of
Neuropsychological Status (RBANS) has received little empirical support, but at
least eight alternative factor structures have been identified in the literature.
The current study used confirmatory factor analysis to compare the original RBANS
model with eight alternatives, which were adjusted to include a general factor.
Participant data were obtained from Project FRONTIER, an epidemiological study of
rural health, and comprised 341 adults (229 women, 112 men) with mean age of 61.2
years (SD = 12.1) and mean education of 12.4 years (SD = 3.3). A bifactor version
of the model proposed by Duff and colleagues provided the best fit to the data
(CFI = 0.98; root-mean-squared error of approximation = 0.07), but required
further modification to produce appropriate factor loadings. The results support
the inclusion of a general factor and provide partial replication of the Duff and
colleagues RBANS model.
PMID- 26429559
TI - Efficacy of memory training in healthy community-dwelling older people: study
protocol for a randomized controlled trial.
AB - BACKGROUND: There is limited evidence on the efficacy and social utility of
cognitive training. To address this, we have designed a randomized controlled
trial to assess the effectiveness of memory training workshops for healthy older
people in terms of their short- and long-term impact on cognitive function,
health-related quality of life, and functionality. METHODS/DESIGN: A randomized
controlled trial will be performed in health care centers in Barcelona (Spain)
through comparison of a group of individuals participating in memory training
workshops (experimental group) with another group with similar characteristics
not participating in the workshops (control group). The intervention will consist
of twelve 90-minute group sessions imparted once a week by a psychologist
specialized in memory training. The groups will each comprise approximately 15
people, for a total number of 230 patients involved in the study. Each session
has its own objectives, materials and activities. The content of the intervention
is based on memory training from different perspectives, including cognitive and
emotional aspects and social and individual skills. Data will be collected at
baseline, at 3-4 months and at 6 months. To assess the efficacy of the
intervention on cognitive function, health-related quality of life and
functionality, a statistical analysis will be performed by fitting a repeated
measures mixed effects model for each main outcome: Self-perceived memory,
measured by a Subjective Self-reported Memory Score (from 0 to 10) and by the
Memory Failures in Everyday life questionnaire (MFE); Everyday memory, measured
using the Rivermead Behavioural Memory Test-3 (RBMT-3) and Executive control
abilities, measured in terms of visual-perceptual ability, working memory and
task-switching ability with the Trail Making Test (TMT) and with the digit span
scale of the Wechsler Adult Intelligence Scale III (WAIS III). DISCUSSION: The
results of this study will be highly useful for social and public health policies
related to older people. Given the continuous increase in the prevalence of older
people, a large number of interventions targeting memory loss are funded by
public resources. To ensure transparency and effective prioritization, research
such as the present study is needed to provide evidence of the effectiveness and
usefulness of these interventions. TRIAL REGISTRATION: Number: NCT02431182 .
PMID- 26429560
TI - Survey on the use of insulin pumps in Italy: comparison between pediatric and
adult age groups (IMITA study).
AB - AIMS: The aim of the study was to evaluate and compare continuous subcutaneous
insulin infusion (CSII) use in pediatric and adult age groups. METHODS: Data were
collected with a questionnaire sent by e-mail to CSII-experienced Diabetes
Centers. The questionnaire assessed: (1) number of CSII-treated patients; (2)
patient demographic data and characteristics; (3) structure and organization of
Diabetes Centers providing CSII therapy; (4) pump characteristics (conventional
pump, sensor-augmented pump); and (5) CSII dropouts. RESULTS: A total of 217 out
of 1093 Italian centers participated: 51 pediatric (23.5 %) and 166 (76.5 %)
adult centers (AP). Compared to a survey performed in 2005, there was a
significant increase in the number of pediatric units when compared to adult
units (112 vs 37 %, respectively, p < 0.05). Pediatric age is characterized by a
greater concern for quality of life and injections, and a higher dropout rate
(10.6 vs 8.9 %) mainly related to pump wearability and site reactions. A complete
diabetes-care team is associated with a superior use of technology (fewer
dropouts, increased CGM and advanced bolus use) which is, however, still used in
a small percentage of patients. CONCLUSIONS: In Italy, the number of CSII-treated
pediatric patients (PP) is growing more significantly when compared to adults.
Only 60 % of all patients are using advanced functions and 20 % are using CGMs
continuously. This confirms the great interest in diabetes technology that is
growing in pediatric diabetologists. However, much improvement is warranted in
the organization and specialized training of pediatric, adult and transitional
facilities.
PMID- 26429561
TI - Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review
and Meta-Analysis.
AB - BACKGROUND: Several clinical trials have reported that therapies targeting
programmed death-1 (PD1) and its ligand (PD-L1) improve patient outcomes, while
tumor response has been related to PD-L1 expression. OBJECTIVE: To investigate
the prognostic role of PD-L1 expression in patients affected by renal cell
carcinoma (RCC). METHODS: MEDLINE/PubMed, the Cochrane Library, and ASCO
University were searched for studies investigating the prognostic role of PD-L1
expression in RCC. Data extraction was conducted according to the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS: Six studies and 1323 cases were included in the final analysis. PD-L1
was expressed in 24.2 % of clear cell tumors compared to 10.9 % of non-clear cell
tumors (p = 0.002). In the overall population, a higher level of PD-L1 expression
increased the risk of death by 81 % (HR; 1.81, 95 % CI 1.31-2.49; p < 0.001).
When the analysis was restricted to cases evaluated by immunohistochemistry
alone, the higher expression of PD-L1 more than doubled the risk of death (HR;
2.05, 95 % CI 1.38-3.05; p < 0.001). In clear cell histology, higher PD-L1
expression increased the risk of death by 53 % (HR; 1.53, 95 % CI 1.27-1.84; p <
0.001), while in metastatic patients, the evaluation of PD-L1 expression on
primary tumors revealed that it retains its prognostic role (HR; 1.45, 95 % CI
1.08-1.93; p = 0.01). LIMITATIONS: Significant heterogeneity has been identified
among the included studies. As a consequence, cautious interpretation of the
results is recommended. CONCLUSION: This meta-analysis indicates that a higher
level of PD-L1 expression is a negative prognostic factor in RCC. Its validation
as an independent prognostic factor compared to other traditionally used clinical
parameters in localized or advanced disease is recommended.
PMID- 26429562
TI - PyMine: a PyMOL plugin to integrate and visualize data for drug discovery.
AB - BACKGROUND: Tremendous amount of chemical and biological data are being generated
by various high-throughput biotechnologies that could facilitate modern drug
discovery. However, lack of integration makes it very challenging for individual
scientists to access and understand all the data related to a specific protein of
interest. FINDINGS: To overcome this challenge, we developed PyMine, a PyMOL
plugin that retrieves chemical, structural, pathway and other related biological
data of a receptor and small molecules from a variety of high-quality databases
and presents them in a graphic and uniformed way. CONCLUSIONS: Developed as an
interactive and user-friendly tool, PyMine can be used as a central data-hub for
users to access and visualize multiple types of data and to generate new ideas
intuitively for structure-based molecule design.
PMID- 26429563
TI - Dyscholesterolemia Protects Against Ischemia-Induced Ventricular Arrhythmias.
AB - BACKGROUND: Hypercholesterolemia protects against ventricular fibrillation in
patients with myocardial infarction. We hypothesize that hypercholesterolemia
protects against ischemia-induced reentrant arrhythmias because of altered ion
channel function. METHODS AND RESULTS: ECGs were measured in low-density
lipoprotein receptor knockout (LDLr(-/-)), apolipoprotein A1 knockout (ApoA1(-/
)), and wild-type (WT) mice. Action potentials, calcium handling, and ion
currents were recorded in ventricular myocytes. Gene expression was determined by
quantitative polymerase chain reaction and Western blot. In isolated perfused
hearts, regional ischemia was induced and arrhythmia inducibility was tested.
Serum low-density lipoprotein (LDL) cholesterol was higher in LDLr(-/-) mice than
in WT mice (2.6 versus 0.4 mmol/L), and high-density lipoprotein cholesterol was
significantly lower in ApoA1(-/-) mice than in WT mice (0.3 versus 1.8 mmol/L).
LDLr(-/-) and ApoA1(-/-) myocytes contained more cholesterol than WT (34.4+/-2.8
and 36.5+/-2.4 versus 25.5+/-0.4 MUmol/g protein). The major potassium currents
were not different in LDLr(-/-) and ApoA1(-/-) compared with WT mice. The L-type
calcium current (I(Ca)), however, was larger in LDLr(-/-) and ApoA1(-/-) than in
WT (12.1+/-0.7 and 12.8+/-0.8 versus 9.4+/-1.1 pA/pF). Calcium transient
amplitude and fractional sarcoplasmic reticulum calcium release were larger and
action potential and QTc duration longer in LDLr(-/-) and ApoA1(-/-) than in WT
mice (action potential duration at 90% of repolarization: 102+/-4 and 106+/-3
versus 84+/-3.1 ms; QTc: 50.9+/-1.3 and 52.8+/-0.8 versus 43.5+/-1.2 ms). During
ischemia, ventricular tachycardia/ventricular fibrillation inducibility was
larger in WT than in LDLr(-/-) and ApoA1(-/-) hearts. Expression of sodium
channel and Ca-handling genes were not significantly different between groups.
CONCLUSIONS: Dyscholesterolemia is associated with action potential prolongation
because of increased I(Ca) and reduces occurrence of reentrant arrhythmias during
ischemia.
PMID- 26429564
TI - Impact of 30 mg/kg amikacin and 8 mg/kg gentamicin on serum concentrations in
critically ill patients with severe sepsis.
AB - OBJECTIVES: Low first-dose peak serum concentrations of amikacin and gentamicin
are commonly reported in ICU patients. The present study aimed to assess whether
30 mg/kg amikacin or 8 mg/kg gentamicin achieved target concentrations in ICU
patients with severe sepsis. PATIENTS AND METHODS: Sixty-three ICU patients
(Simplified Acute Physiology Score II = 43 +/- 16) with severe sepsis and an
indication for intravenous amikacin (n = 47) or gentamicin (n = 16) were
included. The first (30 mg/kg amikacin; 8 mg/kg gentamicin) and subsequent doses
and corresponding peak concentrations (30 min after the completion of an
infusion) were recorded. French guideline target concentrations were >=60 and
>=30 mg/L for amikacin and gentamicin, respectively. A target
pharmacokinetic/pharmacodynamic ratio of 10 * MIC was also measured. RESULTS:
Pulmonary, abdominal and urinary tract infections were diagnosed in 56 patients.
Infection was confirmed in 37 patients (59%). The targeted first-dose peak
concentration was achieved in 37/63 patients (59%) [amikacin 36/47 (77%) and
gentamicin 1/16 (6%)], and 59/63 patients (94%) achieved the
pharmacokinetic/pharmacodynamic ratio using the MIC data that were available from
21 patients. However, the second dose of aminoglycoside was withheld because of
high trough concentrations in nearly half of patients who did not have renal
dysfunction. CONCLUSIONS: In this study, 30 mg/kg amikacin and 8 mg/kg gentamicin
led to target peak serum concentrations in 59% of patients.
PMID- 26429565
TI - Amiodarone increases positive-strand RNA virus replication in vitro: implications
for its use in patients with viral infections.
PMID- 26429566
TI - Educating healthcare professionals in antimicrobial stewardship: can online
learning solutions help?
AB - Education is widely recognized as one of the cornerstones of successful
antimicrobial stewardship programmes. There is evidence of important knowledge
flaws around antimicrobial prescribing among both medical students and
clinicians. Educational interventions improve antimicrobial prescribing, but
traditional tools may be insufficient to deliver training to meet the complex
demands of global healthcare professionals working across a diverse range of
healthcare and resource settings. The educational solutions increasingly need to
be timely, efficient, pragmatic, high quality, aligned to the needs of the
professional in a specific context, sustainable and cost-effective. Online
learning has been playing a growing role in education about antimicrobial
stewardship and the recent phenomenon of massive open online courses (MOOCs)
offers novel and additional opportunities to deliver relevant information to a
wide range of people. Additional research on MOOCs as an educational approach is
needed in order to define their effectiveness, sustainability and the best ways
to achieve the intended results. Although the precise value of new online
strategies such as MOOCs is ill defined, they certainly will have an important
place in increasing awareness and improving antimicrobial prescribing.
PMID- 26429567
TI - Mechanical debridement versus radiofrequency in knee chondroplasty with
concomitant medial meniscectomy: 10-year results from a randomized controlled
study.
AB - PURPOSE: We compared the effectiveness of mechanical debridement (MD) and bipolar
radiofrequency chondroplasty (RF) with regard to clinical outcome, rate of
revision, and progression of knee osteoarthritis. METHODS: Sixty patients with
MRI-detected grade III cartilage lesions on the medial femoral condyle were
considered for the study. For MD (group 1; n = 30), each lesion was debrided
using a mechanical shaver. For RF (group 2; n = 30), each lesion was smoothed
using a temperature-controlled RF probe set at 50 degrees C. RESULTS: The 10
year follow-up was available for 47 patients (78.3 %). Sixty per cent of group 1
(n = 18) underwent revision during the follow-up period. In contrast, the
revision rate in group 2 was 23.3 % (n = 7; p = 0.061). The mean survival was
94.1 months (95 % CI 77.1-111.3) and 62.5 months (95 % CI 45.9-79.2) for group 2
and group 1, respectively. Patients who did not require revision (group 1, n = 9;
group 2, n = 13) were assessed before surgery and 1, 4, and 10 years after
surgery using the knee injury and osteoarthritis outcome score (KOOS). At follow
up, the KOOS was higher for group 2 than group 1. At the time of surgery, no
patient showed any radiological signs of osteoarthritis. The width of the medial
joint was 5.4 mm (95 % CI 4.3-6.5) and 5.6 mm (95 % CI 4.9-6.3) in the MD and RF
groups, respectively (n.s.). During the follow-up period, the joint space width
narrowed continuously in both groups (p < 0.001), but more rapidly in the group 1
(n.s). CONCLUSION: Compared to conventional MD, 50 degrees RF treatment appears
to be a superior method based on short- and medium-term clinical outcomes and the
progression of knee osteoarthritis. Clear predictors for the indications of
different cartilage treatments and more randomized clinical trials are needed.
LEVEL OF EVIDENCE: I.
PMID- 26429568
TI - Ischiofemoral impingement and hamstring dysfunction as a potential pain generator
after ischial tuberosity apophyseal fracture non-union/malunion.
AB - PURPOSE: The purpose of this study was to describe the occurrence of
ischiofemoral impingement (IFI) and hamstring dysfunction following malunion or
non-union of ischial tuberosity apophyseal avulsion fractures and report the
short-term outcomes of surgical treatment with regard to alleviating symptomatic
extra-articular impingement. METHODS: All patients who underwent surgery for
recalcitrant hip and buttock pain in the setting of prior ischial tuberosity
avulsion fracture at three tertiary-level hip preservation centres were included
for this review. A total of ten patients met our inclusion criteria and underwent
sciatic neurolysis, resection of the ischial tuberosity fragment and hamstring
reattachment. Clinical outcomes scores were collected post-operatively including
the Modified Harris Hip Score (mHHS) and the Hip Outcomes Score (HOS). RESULTS:
Ten patients with a mean age of 18 years (range 14-28) underwent surgery for
symptomatic ischiofemoral impingement after ischial tuberosity avulsion fracture.
At a mean of 2.2-year follow-up (range 1.7-3.5), the median post-operative mHHS
was 89.7 (65.7-96.8) and HOS ADL and Sport subscales were 90 % or greater in all
cases. Five patients (50 %) rated their hip as normal, and five patients (50 %)
rated their hip as near normal. CONCLUSION: Malunion or non-union following
ischial tuberosity apophyseal fracture can lead to IFI and hamstring dysfunction.
Clinically, the resultant pain and dysfunction is often chronic, and can be
debilitating. In select cases, a reliable surgical technique is presented to
improve hamstring function and correct ischiofemoral impingement in this setting
with good-to-excellent outcomes in the majority of cases at short-term follow-up.
LEVEL OF EVIDENCE: IV.
PMID- 26429569
TI - Thought Disorder in Preschool Children with Attention Deficit/Hyperactivity
Disorder (ADHD).
AB - Preschool identification of and intervention for psychiatric symptoms has the
potential for lifelong benefits. However, preschool identification of thought
disorder, a symptom associated with long term risk for social and cognitive
dysfunction, has received little attention with previous work limited to
examining preschoolers with severe emotional and behavioral dysregulation. Using
story-stem methodology, 12 children with ADHD and 12 children without ADHD, ages
4.0-6.0 years were evaluated for thought disorder. Thought disorder was reliably
assessed (Cronbach's alpha = .958). Children with ADHD were significantly more
likely than children without ADHD to exhibit thought disorder (75 vs 25 %;
Fischer's Exact Test = .0391). Thought disorder can be reliably assessed in
preschool children and is present in preschool children with psychiatric illness
including preschool children with ADHD. Thought disorder may be identifiable in
preschool years across a broad range of psychiatric illnesses and thus may be an
appropriate target of intervention.
PMID- 26429570
TI - Moderating Effects of Gender on Outcomes Associated with Stressful Life Events
Among Elementary School-Age Youth.
AB - Stressful life events have been associated with child and adolescent
maladjustment, including elevated levels of aggression and anxiety (Attar et al.
in J Clin Child Psychol 23:391-400, 1994; Fox et al. in J Adolesc 33:43-54,
2010). However, gender specific outcomes associated with stressful life events
among elementary school-age youth are less known. Accordingly, the current study
examined the role of gender in the associations between stressful life events and
anxiety and proactive and reactive aggression. Participants included 294
elementary school-age children (M = 8.71, SD = 1.17, 50.7 % male). Regression
analyses indicated that stressful life events were positively associated with
anxiety and reactive, but not proactive, aggression. There were no gender
differences with regard to the associations with anxiety symptoms or proactive
aggression. However, gender moderated the association between stressful life
events and reactive aggression, such that stressful life events were only
positively associated with reactive aggression for boys. Future directions and
implications of this research are presented.
PMID- 26429571
TI - Vitamin D supplementation and systemic inflammation in relapsing-remitting
multiple sclerosis.
AB - Observational studies have suggested that vitamin D may reduce inflammation in
relapsing-remitting multiple sclerosis (RRMS), but this has not been clearly
confirmed in randomized controlled trials. To further explore the possible anti
inflammatory effects of vitamin D in RRMS, we examined the effect of high-dose
oral vitamin D3 on eleven markers of systemic inflammation in 68 RRMS patients
enrolled in a double-blinded randomized placebo-controlled trial of vitamin D3
supplementation (20,000 IU/week) (NCT00785473). Serum inflammation markers and 25
hydroxyvitamin D (25(OH)D) were measured at baseline and week 96, and no
restrictions were set on additional standard immunomodulatory treatment for RRMS.
The mean 25(OH)D level rose from 56 +/- 29 to 123 +/- 34 nmol/L among patients
receiving vitamin D3 supplementation, whereas only a minor increase from 57 +/-
22 to 63 +/- 24 nmol/L was seen in the placebo group. However, no significant
differences appeared between the vitamin D group and the placebo group for any of
the inflammation markers. Patients on immunomodulatory therapy had significantly
higher levels of interleukin-1 receptor antagonist and chemokine (C-X-C motif)
ligand 16 than patients without immunomodulatory treatment, but there were no
clear synergistic effects between immunomodulatory therapy and vitamin D3
supplementation on any of the inflammation markers. The rise in 25(OH)D levels
after vitamin D3 supplementation was unaffected by immunomodulatory treatment. We
conclude that in this study of RRMS patients, high-dose oral vitamin D3
supplementation prominently increased serum 25(OH)D levels without affecting
markers of systemic inflammation, while a more anti-inflammatory phenotype was
found among patients on immunomodulatory treatment.
PMID- 26429572
TI - Complications are reduced with a protocol to standardize timing of fixation based
on response to resuscitation.
AB - BACKGROUND: Our group developed a protocol, entitled Early Appropriate Care
(EAC), to determine timing of definitive fracture fixation based on presence and
severity of metabolic acidosis. We hypothesized that utilization of EAC would
result in fewer complications than a historical cohort and that EAC patients with
definitive fixation within 36 h would have fewer complications than those treated
at a later time. METHODS: Three hundred thirty-five patients with mean age 39.2
years and mean Injury Severity Score (ISS) 26.9 and 380 fractures of the femur (n
= 173), pelvic ring (n = 71), acetabulum (n = 57), and/or spine (n = 79) were
prospectively evaluated. The EAC protocol recommended definitive fixation within
36 h if lactate <4.0 mmol/L, pH >=7.25, or base excess (BE) >=-5.5 mmol/L.
Complications including infections, sepsis, DVT, organ failure, pneumonia, acute
respiratory distress syndrome (ARDS), and pulmonary embolism (PE) were identified
and compared for early and delayed patients and with a historical cohort.
RESULTS: All 335 patients achieved the desired level of resuscitation within 36 h
of injury. Two hundred sixty-nine (80%) were treated within 36 h, and 66 had
protocol violations, treated on a delayed basis, due to surgeon choice in 71%.
Complications occurred in 16.3% of patients fixed within 36 h and in 33.3% of
delayed patients (p = 0.0009). Hospital and ICU stays were shorter in the early
group: 9.5 versus 17.3 days and 4.4 versus 11.6 days, respectively, both p <
0.0001. This group of patients when compared with a historical cohort of 1443
similar patients with 1745 fractures had fewer complications (16.3 versus 22.1%,
p = 0.017) and shorter length of stay (LOS) (p = 0.018). CONCLUSIONS: Our EAC
protocol recommends definitive fixation within 36 h in resuscitated patients.
Early fixation was associated with fewer complications and shorter LOS. The EAC
recommendations are safe and effective for the majority of severely injured
patients with mechanically unstable femur, pelvis, acetabular, or spine fractures
requiring fixation.
PMID- 26429573
TI - The Afro-Cardiac Study: Cardiovascular Disease Risk and Acculturation in West
African Immigrants in the United States: Rationale and Study Design.
AB - Cardiovascular disease (CVD) remains the leading cause of death in the United
States (US). African-descent populations bear a disproportionate burden of CVD
risk factors. With the increase in the number of West African immigrants (WAIs)
to the US over the past decades, it is imperative to specifically study this new
and substantial subset of the African-descent population and how acculturation
impacts their CVD risk. The Afro-Cardiac study, a community-based cross-sectional
study of adult WAIs in the Baltimore-Washington metropolis. Guided by the PRECEDE
PROCEED model, we used a modification of the World Health Organization Steps
survey to collect data on demographics, socioeconomic status, migration-related
factors and behaviors. We obtained physical, biochemical, acculturation
measurements as well as a socio-demographic and health history. Our study
provides critical data on the CVD risk of WAIs. The framework used is valuable
for future epidemiological studies addressing CVD risk and acculturation among
immigrants.
PMID- 26429574
TI - Patient Activation is Inconsistently Associated with Positive Health Behaviors
Among Obese Safety Net Patients.
AB - We examine the association of patient activation and physical activity and fruit
and vegetable consumption among obese safety net patients. Adult obese patients
(n = 198) of three safety net clinics completed a survey assessing patient
activation, physical activity, fruit and vegetable consumption, care experiences,
and health status. Multivariate logistic regression models incrementally assessed
the adjusted relation of patient activation and physical activity and fruit and
vegetable consumption. In adjusted analyses, higher activated patients had higher
odds [Odds ratio (OR) 1.58, p < 0.01] of consuming fruits and vegetables daily
than less activated patients. There was no significant association between
patient activation and regular physical activity. Engaging in regular physical
activity appears to be difficult, even for highly activated patients. In
contrast, additional fruit and vegetable consumption is a relatively easier
change. Patient activation was inconsistently associated with two positive health
behaviors among obese safety net patients.
PMID- 26429578
TI - Colored Sticky Traps to Selectively Survey Thrips in Cowpea Ecosystem.
AB - The bean flower thrips, Megalurothrips usitatus (Bagrall) (Thysanoptera:
Thripidae), is an important pest of legume crops in South China. Yellow, blue, or
white sticky traps are currently recommended for monitoring and controlling
thrips, but it is not known whether one is more efficient than the other or if
selectivity could be optimized by trap color. We investigated the response of
thrips and beneficial insects to different-colored sticky traps on cowpea, Vigna
unguiculata. More thrips were caught on blue, light blue, white, and purple traps
than on yellow, green, pink, gray, red, or black traps. There was a weak
correlation on the number of thrips caught on yellow traps and survey from
flowers (r = 0.139), whereas a strong correlation was found for blue traps and
thrips' survey on flowers (r = 0.929). On commercially available sticky traps
(Jiaduo(r)), two and five times more thrips were caught on blue traps than on
white and yellow traps, respectively. Otherwise, capture of beneficial insects
was 1.7 times higher on yellow than on blue traps. The major natural enemies were
the predatory ladybird beetles (63%) and pirate bugs Orius spp. (29%), followed
by a number of less representative predators and parasitoids (8%). We conclude
the blue sticky trap was the best to monitor thrips on cowpea in South China.
PMID- 26429577
TI - Are there differences between stemless and conventional stemmed shoulder
prostheses in the treatment of glenohumeral osteoarthritis?
AB - BACKGROUND: Conventional stemmed anatomical shoulder prostheses are widely used
in the treatment of glenohumeral osteoarthritis. The stemless shoulder
prosthesis, in contrast, is a new concept, and fewer outcome studies are
available. Therefore, the purpose of the study was to investigate the early
functional outcome and postoperative proprioception of a stemless prosthesis in
comparison with a standard stemmed anatomic shoulder prosthesis. METHODS: Twelve
patients (mean age 68.3 years [SD +/- 5.4]; 5 female, 7 male) with primary
glenohumeral osteoarthritis of the shoulder were enrolled, who underwent total
shoulder arthroplasty (TSA) with a stemless total shoulder prosthesis, Total
Evolution Shoulder System (TESS; Biomed, France). The control group consisted of
twelve (age and gender matched) patients (mean age 67.8 years; [SD +/- 7.1]; 9
female, 3 male), getting a TSA with a standard anatomic stemmed prosthesis,
Aequalis Shoulder (Tournier, Lyon, France). Patients were examined the day before
and six months after surgery. The pre- and postoperative Constant Score (CS) was
evaluated and proprioception was measured in a 3D video motion analysis study
using an active angle-reproduction (AAR) test. RESULTS: Comparing the
postoperative CS, there was no significant difference between the groups treated
with the TESS prosthesis (48.0 +/- 13.8 points) and the Aequalis prosthesis (49.3
+/- 8.6 points; p = 0.792). There was no significant difference in postoperative
proprioception between the TESS group (7.2 degrees [SD +/- 2.8]) and the
Aequalis group(8.7 degrees [SD +/- 2.7]; p = 0.196), either. Comparison of in
the results of CS and AAR test pre- and postoperatively showed no significant
differences between the groups. DISCUSSION: In patients with glenohumeral
osteoarthritis, treated with TSA, the functional and the proprioceptive outcome
is comparable between a stemless and a standard stemmed anatomic shoulder
prosthesis at early followup. CONCLUSION: Further follow-up is necessary
regarding the long-term performance of this prosthesis. TRIAL REGISTRATION:
Current Controlled Trials DRKS 00007528 . Registered 17 November 2014.
PMID- 26429579
TI - Neotropical Polistinae (Vespidae) and the Progression Rule Principle: the Round
Trip Hypothesis.
AB - The progression rule principle is based on the relation between centers of origin
and basal forms, and the prediction that recently colonized areas are where
novelties commonly occur. Using this concept as the null hypothesis, the aim of
the present study was to test whether intuitive predictions of this model are
confirmed in the Neotropical paper wasps, a group fairly studied through
phylogenetic frameworks. The analyses consisted of a careful review of the
distribution of different wasps of the subfamily Polistinae with available
phylogenies and the association of this information with colonization routes.
This procedure allowed the determination of a two-step colonization process in
the Neotropical region based on the progression rule principle, for which the
round-trip hypothesis is proposed. The first route (east to west) is seen in a
small group of Polistes. This route is rare but strengthens the arising of paper
wasps in the Americas in a Gondwanan scenario. The second route (west to east) is
remarkably repeated in several other lineages. Thus, the northwestern Neotropics,
mainly Amazon Forest, is proposed as the major center of origins for living
Neotropical Polistinae and the round-trip hypothesis may explain both earlier and
later colonization routes of the paper wasps analyzed.
PMID- 26429580
TI - Immature Development of Spodoptera dolichos (Fabricius) (Lepidoptera: Noctuidae).
AB - We provide detailed temporal and morphological parameters of the immature stages
of Spodoptera dolichos (Fabricius) larvae fed on artificial diet under controlled
conditions (25 +/- 1 degrees C, 70 +/- 10% RH, and 14 h photophase). The
viability of the egg, larval, pupal, and prepupal stages was 97.5%, 97.0%, 93.1%,
and 98.9%, respectively. The average duration of the egg, larval, prepupal, and
pupal stages was 5.0, 23.4, 3.2, and 21.5 days, respectively. Females took longer
at the larval stage than males, with 10.5% of them having seven instars. The
growth rate of female larvae that developed through six and seven instars was
1.72 and 1.54, respectively. Female pupae were significantly larger, exhibiting
slower development than males.
PMID- 26429581
TI - Did Adult Diurnal Activity Influence the Evolution of Wing Morphology in Opoptera
Butterflies?
AB - The butterfly genus Opoptera includes eight species, three of which have diurnal
habits while the others are crepuscular (the usual activity period for members of
the tribe Brassolini). Although never measured in the field, it is presumed that
diurnal Opoptera species potentially spend more time flying than their
crepuscular relatives. If a shift to diurnal habits potentially leads to a higher
level of activity and energy expenditure during flight, then selection should
operate on increased aerodynamic and energetic efficiency, leading to changes in
wing shape. Accordingly, we ask whether diurnal habits have influenced the
evolution of wing morphology in Opoptera. Using phylogenetically independent
contrasts and Wilcoxon rank sum tests, we confirmed our expectation that the
wings of diurnal species have higher aspect ratios (ARs) and lower wing centroids
(WCs) than crepuscular congeners. These wing shape characteristics are known to
promote energy efficiency during flight. Three Opoptera wing morphotypes
established a priori significantly differed in AR and WC values. The crepuscular,
cloud forest dweller Opoptera staudingeri (Godman & Salvin) was exceptional in
having an extended forewing tip and the highest AR and lowest WC within Opoptera,
possibly to facilitate flight in a cooler environment. Our study is the first to
investigate how butterfly wing morphology might evolve as a response to a
behavioral shift in adult time of activity.
PMID- 26429582
TI - Hemocytes of the Rose Sawfly Arge ochropus (Gmelin) (Hymenoptera: Argidae).
AB - We characterized individual morphological types of the rose sawfly, Arge ochropus
(Gmelin) (Hymenoptera: Argidae), hemocytes for the first time by means of light
and differential interference contrast microscopy and scanning and transmission
electron microscopy. Four types of hemocytes were identified in the hemolymph of
larvae and pupae of A. ochropus: prohemocytes, plasmatocytes, granulocytes, and
oenocytoids. Prohemocytes are the smallest type of hemocytes, rounded to ovoid
cells with large nuclei. Plasmatocytes are polymorphic and variable in size.
Granulocytes are oval and spherical cells variable in size, with variable number
of rough endoplasmic reticulum, mitochondria, and microtubules in the cytoplasm.
Oenocytoids contain eccentric nucleus and cytoplasm with small mitochondria and
few rough endoplasmic reticula. Differential hemocyte counts indicated that
plasmatocytes are the most abundant hemocyte type during early instars while
granulocytes are the most abundant hemocyte type in the last instar. The pattern
of total hemocyte count changed during rose sawfly development and reached its
peak in prepupae and then declined slowly in the pupal stage.
PMID- 26429583
TI - Long-Term Outcomes of Iris-sutured Posterior Chamber Intraocular Lenses in
Children.
AB - PURPOSE: To report the long-term outcomes and complications of iris-sutured
posterior chamber intraocular lenses (PCIOLs) in the pediatric population.
DESIGN: Retrospective interventional case study. METHODS: This study involved 12
consecutive pediatric patients (17 eyes) who underwent placement of foldable iris
sutured PCIOLs between September 2004 and September 2007. Outcome measures
included change in visual acuity and complications. RESULTS: Of the 17 eyes were
reviewed, 6 (35%) had hereditary or idiopathic ectopia lentis, 5 (29%) had Marfan
syndrome, 2 (12%) were aphakic after pars plana vitrectomy and 4 (24%) were
aphakic after surgical intervention for trauma. Average follow-up was 4.69 +/-
3.21 years and mean age of surgery was 7.21 +/- 3.78 years. Seven eyes suffered
dislocation of the PCIOL an average of 12.11 +/- 11.97 months after surgery, with
2 patients undergoing dislocation a second time. There was a higher rate of
dislocation in patients with a history of ectopia lentis due to Marfan syndrome,
idiopathic causes, or hereditary causes than in patients being treated for
aphakia resulting from other causes (71% vs 29%). Mean visual acuity improved in
12 of 17 patients (71%), from 0.80 +/- 0.6 logMAR preoperatively to 0.35 +/- 0.5
logMAR at most recent visit, P = .009. One eye of a Marfan patient sustained a
retinal detachment 8 months after dislocation of the PCIOL, and 1 patient
experienced iris capture of the PCIOL after surgery. CONCLUSIONS: Iris-sutured
intraocular lenses have been used as an alternative to transsclerally sutured
intraocular lenses to correct aphakia in pediatric patients. Dislocation of the
intraocular lenses can occur frequently, however. The procedure should be
considered with caution in pediatric patients.
PMID- 26429584
TI - Outcomes of 27 Gauge Microincision Vitrectomy Surgery for Posterior Segment
Disease.
AB - PURPOSE: To report the initial experience, clinical outcomes, and safety profile
of 27 gauge pars plana vitrectomy (PPV) in eyes with posterior segment disease.
DESIGN: Multicenter, retrospective, interventional case series. METHODS: setting:
Private practice and tertiary care settings. STUDY POPULATION: Eyes undergoing 27
gauge PPV for a vitreoretinal surgery indication. INTERVENTION: Three-port,
transconjunctival 27 gauge PPV. MAIN OUTCOME MEASURES: Change in visual acuity
and occurrence of intraoperative and postoperative complications with minimum
follow-up of 90 days. RESULTS: Ninety-five eyes met the inclusion criteria.
Surgical indications included epiretinal membrane (n = 26), diabetic tractional
retinal detachment (n = 14), full-thickness macular hole (n = 11), rhegmatogenous
retinal detachment with (n = 7) or without (n = 9) proliferative
vitreoretinopathy (PVR), vitreous hemorrhage (n = 10), vitreous opacities (n =
8), endophthalmitis (n = 4), sub-silicone oil retinal detachment (n = 3),
retained lens material (n = 1), submacular hemorrhage (n = 1), and aqueous
misdirection (n = 1). Mean logMAR visual acuity improved from 1.08 +/- 0.71
(20/240 Snellen equivalent) preoperatively to 0.53 +/- 0.65 (20/67 Snellen
equivalent) postoperatively (P < .001). Mean follow-up was 144 days (median 127
days, range 90-254 days). There were no intraoperative complications and no case
required conversion to 20, 23, or 25 gauge instrumentation. A total of 3
sclerotomy sites (1.1%) were sutured at the conclusion of surgery. Postoperative
complications included transient ocular hypertension in 8 eyes (8.4%), transient
hypotony in 5 eyes (5.3%), and vitreous hemorrhage in 5 eyes (5.3%). No cases of
postoperative endophthalmitis, sclerotomy-related retinal tears, or choroidal
detachments were encountered in the follow-up period. CONCLUSION: The 27 gauge
PPV was well tolerated with low rates of intraoperative and postoperative
complications across varied surgical indications.
PMID- 26429585
TI - Regenerated Cellulose Capsules for Controlled Drug Delivery, Part 2: Modulating
Membrane Permeability by Incorporation of Depolymerized Cellulose and Altering
Membrane Thickness.
AB - For application of regenerated cellulose (RC) membranes in capsule dosage forms,
the methods to modify drug release from these membranes are described. Membranes
were fabricated by blending native and depolymerized celluloses dissolved in
dimethyl sulfoxide and paraformaldehyde solvent system, prior to casting on
molds, precipitation in water, and thermal annealing. The effect of laminating
layers of RC to fabricate membranes with increasing thickness was also
investigated. Solute diffusion studies using ionic and hydrophobic solutes, as
well as large protein molecules, were conducted in side-by-side diffusion cells.
Microscopic as well as physiological evaluation of these membranes indicated that
pore size, porosity, and water uptake decreased as the fraction of depolymerized
cellulose increased in the membranes. Permeability analysis of small ionic and
hydrophobic solutes indicated that the solute transport across the hydrated
membrane occurs through diffusion in the water-filled pores that are formed in
situ. The apparent path for solute diffusion increases as the fraction of
depolymerized cellulose increases. Permeability analysis of large protein
molecules indicated that the pore sizes and distribution in these membranes is
heterogeneous. Increasing the membrane thickness by lamination of RC does not
influence porosity but causes formation of dead-end pores because of blocking by
subsequent laminate layers.
PMID- 26429586
TI - Quantitative Assessment of Scalene Muscle Block for the Diagnosis of Suspected
Thoracic Outlet Syndrome.
AB - PURPOSE: To measure changes in upper limb work and power capacity before and
after anterior scalene muscle block (ASMB) to suggest thoracic outlet syndrome
caused by costoclavicular space compression. METHODS: We evaluated 34 patients
disabled by symptoms suggesting thoracic outlet syndrome. An ASMB was performed
via a supraclavicular injection. The sternocleidomastoid muscle was injected as a
control. We captured data obtained from work simulator measurements before and
after ASMB. Each patient performed a push-pull test with the forearm at waist
level (test 1), an overhead bar push-pull test with the arm elevated (test 2),
and the extremity abduction stress test with repetitive hand gripping during
static arm elevation (test 3). We measured the work product, time to fatigue, and
power generation. Sensory testing was performed after ASMB to rule out improved
performance associated with possible sensory nerve block. RESULTS: In contrast to
sternocleidomastoid injection controls, symptomatic and functional improvement
was noted in all patients (n = 34) after ASMB. Work product measurement improved
93%, 108%, and 104% for tests 1, 2, and 3, respectively. Time to fatigue and
power output also increased after the block. CONCLUSIONS: Temporary symptomatic
improvement after ASMB may be anticipated in patients with TOS. This study
documents a significant concurrent increase in upper limb motor function after
the block. Increased work and power measurements after ASMB may draw diagnostic
inference regarding a dynamic change in the scalene muscle and the
costoclavicular space associated with symptomatic thoracic outlet syndrome. TYPE
OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.
PMID- 26429587
TI - A new method for segmentation of FDG PET metabolic tumour volume using the
peritumoural halo layer and a 10-step colour scale. A study in patients with
papillary thyroid carcinoma.
AB - AIM: We observed a layer between tumour activity and background on FDG PET/CT
with the 10-step colour scale and the window level set properly. We named the
layer peritumoral halo layer (PHL). We performed this study to establish the
reliability of metabolic tumor volume (MTV) segmentation using PHL (MTV(PHL)) in
patients with papillary thyroid carcinoma. PATIENTS, METHODS: Of a total of 140
papillary thyroid carcinoma (PTC) patients, 70 (50.0%) had FDG-avid PTC. In these
patients, MTV(PHL), MTV segmented according to fixed 50% SUVmax (MTV(50%)), and
fixed SUV with 2.5 to 4.0 (MTV(2.5) to MTV(4.0)) were compared with pathologic
tumour volume (PTV). The absolute percentage difference between MTV(PHL) and PTV
was compared in micropapillary carcinoma (MPTC) and non-micropapillary carcinoma
(non-MPTC) subgroups. The % SUVmax and SUV thresholds of MTV(PHL) were compared
with tumour SUVmax. RESULTS: Among the MTVs, MTV(50%) was not correlated with PTV
(r = -0.16, p = 0.182) and was not reliable according to the Bland-Altman plot.
Although MTV(2.5), MTV(3.0), MTV(3.5), and MTV(4.0) correlated with PTV (r =
0.85, 0.86, 0.87, and 0.87, respectively; p < 0.001), these MTVs were not
reliable on Bland-Altman analyses. MTV(PHL) was significantly correlated with PTV
(r = 0.80, p < 0.001), and the Bland-Altman plot did not show systemic error. The
MTV(PHL) was more accurate in non-MPTC than in MPTC (p < 0.001), and the absolute
% difference was smaller as PTV became larger (sigma = -0.65, p < 0.001). The
MTV(PHL) thresholds had correlations with SUVmax (% SUVmax threshold: sigma =
0.87, p < 0.001; SUV threshold: r = 0.88, p < 0.001). CONCLUSIONS: MTV(PHL) was
more reliable than MTV(%SUVmax) or MTV(SUV). The reliability of MTV(PHL) improved
with larger PTVs. The threshold of the MTV(PHL) was naturally altered by PHL
according to SUVmax.
PMID- 26429589
TI - Current Concepts on Diagnosis and Prognosis of Arrhythmogenic Right Ventricular
Cardiomyopathy/Dysplasia.
AB - Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an uncommon
cardiac disease characterized by progressive right ventricular dysfunction due to
fibrofatty replacement of myocytes and risk of sudden cardiac death from
malignant arrhythmias. ARVC/D is a disease of the cardiac desmosome, with genetic
mutations in genes encoding proteins critical to this structure found in the
majority of patients. The diagnosis of ARVC/D is based on fulfilling a
combination of clinical, imaging, pathologic, and/or genetic criteria set forth
by the 2010 modified Task Force Criteria. Cardiac magnetic resonance (CMR) is
included in these criteria and plays an important role in the management of
ARVC/D, demonstrating pathologic structural changes in the right and left
ventricles that provide both diagnostic and prognostic information. The purpose
of this article is to provide a background on the pathophysiology and genetics of
ARVC/D and focus on the role of CMR in management of ARVC/D including diagnosis,
prognosis, and treatment decisions. Common CMR pitfalls that can lead to
misdiagnosis will also be reviewed.
PMID- 26429588
TI - Current Smoking Status Is Associated With Lower Quantitative CT Measures of
Emphysema and Gas Trapping.
AB - PURPOSE: The purposes of this study were to evaluate the effect of smoking status
on quantitative computed tomography CT measures of low-attenuation areas (LAAs)
on inspiratory and expiratory CT and to provide a method of adjusting for this
effect. MATERIALS AND METHODS: A total of 6762 current and former smokers
underwent spirometry and volumetric inspiratory and expiratory CT. Quantitative
CT analysis was completed using open-source 3D Slicer software. LAAs were defined
as lung voxels with attenuation values <=-950 Hounsfield units (HU) on
inspiratory CT and <=-856 HU on expiratory CT and were expressed as percentage of
CT lung volume (%LAAI-950 and %LAAE-856). Multiple linear regression was used to
determine the effect of smoking status on %LAAI-950 and %LAAE-856 while
controlling for demographic variables, spirometric lung function, and smoking
history, as well as total lung capacity (%LAAI-950) or functional residual
capacity (%LAAE-856). Quantile normalization was used to align the %LAAI-950
distributions for current and former smokers. RESULTS: Mean %LAAI-950 was 4.2+/
7.1 in current smokers and 7.7+/-9.7 in former smokers (P<0.001). After adjusting
for confounders, %LAAI-950 was 3.5 percentage points lower and %LAAE-856 was 6.0
percentage points lower in current smokers than in former smokers (P<0.001).
After quantile normalization, smoking status was an insignificant variable in the
inspiratory regression model, with %LAAI-950 being 0.27 percentage points higher
in current smokers (P=0.13). CONCLUSIONS: After adjusting for patient
demographics and lung function, current smokers display significantly lower %LAAI
950 and %LAAE-856 than do former smokers. Potential methods for adjusting for
this effect would include adding a fixed value (eg, 3.5%) to the calculated
percentage of emphysema in current smokers, or quantile normalization.
PMID- 26429590
TI - Molluscicidal activity of Solanum elaeagnifolium seeds against Galba truncatula
intermediate host of Fasciola hepatica: Identification of beta-solamarine.
AB - CONTEXT: The persistence of fascioliasis in many developing countries urges the
search for simple, cheap, and effective substances. In this view, plants provide
interesting molluscicidal activities thanks to the secondary metabolites they
produce. The genus Solanum is known for its potent effect on vector snails.
OBJECTIVE: The molluscicidal activity of Solanum elaeagnifolium Cav. (Solanaceae)
seeds against Galba truncatula Mull. (Lymnaeidae), intermediate host of Fasciola
hepatica L. (Fasciolidae), was evaluated. MATERIALS AND METHODS: Solanum
elaeagnifolium seeds were powdered and successively extracted using n-hexane,
methylene chloride, acetone, and methanol, for 20 h each. After filtration,
solvents were evaporated. An acid-base treatment was conducted on seed methanolic
extract to isolate total alkaloids and beta-solamarine. Total saponins fraction
was obtained after successive macerations and evaporations. The molluscicidal
activity was evaluated by subjecting snails, in groups of 10, for 48 h to 500 mL
of extracts, fractions, and pure product aqueous solutions, each containing
amounts, ranging from 1 to 50 mg of plant material in 5 mg increments. RESULTS:
The methanolic extract of seeds, beta-solamarine isolated for the first time from
this plant and total saponins fraction showed very potent activities on snails,
giving respective median lethal concentrations (LC50) of 1.18, 0.49, and 0.94
mg/L. Total alkaloids fraction obtained from the methanolic extract was less
active giving an LC50 value of 14.67 mg/L. DISCUSSION AND CONCLUSION: This study
emphasizes that glycoalkaloids and saponins of Solanum elaeagnifolium are potent
molluscicidal agents. Seed methanolic extract, beta-solamarine, and total
saponins fraction may be used as molluscicides.
PMID- 26429591
TI - Innovative use of the integrative review to evaluate evidence of technology
transformation in healthcare.
AB - Healthcare is in a period significant transformational activity through the
accelerated adoption of healthcare technologies, new reimbursement systems that
emphasize shared savings and care coordination, and the common place use of
mobile technologies by patients, providers, and others. The complexity of
healthcare creates barriers to transformational activity and has the potential to
inhibit the desired paths toward change envisioned by policymakers. Methods for
understanding how change is occurring within this complex environment are
important to the evaluation of delivery system reform and the role of technology
in healthcare transformation. This study examines the use on an integrative
review methodology to evaluate the healthcare literature for evidence of
technology transformation in healthcare. The methodology integrates the
evaluation of a broad set of literature with an established evaluative framework
to develop a more complete understanding of a particular topic. We applied this
methodology and the framework of punctuated equilibrium (PEq) to the analysis of
the healthcare literature from 2004 to 2012 for evidence of technology
transformation, a time during which technology was at the forefront of healthcare
policy. The analysis demonstrated that the established PEq framework applied to
the literature showed considerable potential for evaluating the progress of
policies that encourage healthcare transformation. Significant inhibitors to
change were identified through the integrative review and categorized into ten
themes that describe the resistant structure of healthcare delivery: variations
in the environment; market complexity; regulations; flawed risks and rewards;
change theories; barriers; ethical considerations; competition and
sustainability; environmental elements, and internal elements. We hypothesize
that the resistant nature of the healthcare system described by this study
creates barriers to the direct consumer involvement and engagement necessary for
transformational change. Future policies should be directed at removing these
barriers by demanding and emphasizing open technologies and unrestricted access
to data versus as currently prescribed by technology vendors, practitioners, and
policies that perpetuate market equilibrium.
PMID- 26429592
TI - Cluster-based query expansion using external collections in medical information
retrieval.
AB - Utilizing external collections to improve retrieval performance is challenging
research because various test collections are created for different purposes.
Improving medical information retrieval has also gained much attention as various
types of medical documents have become available to researchers ever since they
started storing them in machine processable formats. In this paper, we propose an
effective method of utilizing external collections based on the pseudo relevance
feedback approach. Our method incorporates the structure of external collections
in estimating individual components in the final feedback model. Extensive
experiments on three medical collections (TREC CDS, CLEF eHealth, and OHSUMED)
were performed, and the results were compared with a representative expansion
approach utilizing the external collections to show the superiority of our
method.
PMID- 26429593
TI - The transsexual brain--A review of findings on the neural basis of
transsexualism.
AB - Transsexualism describes the condition when a person's psychological gender
differs from his or her biological sex and is commonly thought to arise from a
discrepant cerebral and genital sexual differentiation. This review intends to
give an extensive overview of structural and functional neurobiological
correlates of transsexualism and their course under cross-sex hormonal treatment.
Research in this field enables insight into the stability or variability of
gender differences and their relation to hormonal status. For a number of
sexually dimorphic brain structures or processes, signs of feminisation or
masculinisation are observable in transsexual individuals, which, during hormonal
treatment, partly seem to further adjust to characteristics of the desired sex.
Still, it appears the data are quite inhomogeneous, mostly not replicated and in
many cases available for male-to-female transsexuals only. As the prevalence of
homosexuality is markedly higher among transsexuals than among the general
population, disentangling correlates of sexual orientation and gender identity is
a major problem. To resolve such deficiencies, the implementation of specific
research standards is proposed.
PMID- 26429594
TI - New WHO guidance on prevention and treatment of maternal peripartum infections.
PMID- 26429595
TI - The effect of lactic acid bacterial starter culture and chemical additives on
wilted rice straw silage.
AB - Lactic acid bacteria (LAB) are suitable for rice straw silage fermentation, but
have been studied rarely, and rice straw as raw material for ensiling is
difficult because of its disadvantages, such as low nutrition for microbial
activities and low abundances of natural populations of LAB. So we investigated
the effect of application of LAB and chemical additives on the fermentation
quality and microbial community of wilted rice straw silage. Treatment with
chemical additives increased the concentrations of crude protein (CP), water
soluble carbohydrate (WSC), acetic acid and lactic acid, reduced the
concentrations of acid detergent fiber (ADF) and neutral detergent fiber (NDF),
but did not effectively inhibit the growth of spoilage organisms. Inoculation
with LABs did not improve the nutritional value of the silage because of poor
growth of LABs in wilted rice straw. Inoculation with LAB and addition of
chemical materials improved the quality of silage similar to the effects of
addition of chemical materials alone. Growth of aerobic and facultatively
anaerobic bacteria was inhibited by this mixed treatment and the LAB gradually
dominated the microbial community. In summary, the fermentation quality of wilted
rice straw silage had improved by addition of LAB and chemical materials.
PMID- 26429596
TI - TiO2 Microboxes with Controlled Internal Porosity for High-Performance Lithium
Storage.
AB - Titanium dioxide (TiO2) is considered a promising anode material for high-power
lithium ion batteries (LIBs) because of its low cost, high thermal/chemical
stability, and good safety performance without solid electrolyte interface
formation. However, the poor electronic conductivity and low lithium ion
diffusivity of TiO2 result in poor cyclability and lithium ion depletion at high
current rates, which hinder them from practical applications. Herein we
demonstrate that hierarchically structured TiO2 microboxes with controlled
internal porosity can address the aforementioned problems for high-power, long
life LIB anodes. A self-templating method for the synthesis of mesoporous
microboxes was developed through Na2 EDTA-assisted ion exchange of CaTiO3
microcubes. The resulting TiO2 nanorods were organized into microboxes that
resemble the microcube precursors. This nanostructured TiO2 material has superior
lithium storage properties with a capacity of 187 mAh g(-1) after 300 cycles at 1
C and good rate capabilities up to 20 C.
PMID- 26429597
TI - A novel cause for primordial dwarfism revealed: defective tRNA modification.
AB - A mutation in the WDR4 gene, coding for a tRNA-modifying enzyme, leads to reduced
levels of guanosine methylation in tRNA in patients with primordial dwarfism.
PMID- 26429598
TI - Clinical indications for augmentation in children with neurogenic urinary
incontinence following bladder outlet procedures: Results of a 14-year
observational study.
AB - PURPOSE: We report continence, upper tract changes, and augmentation indications
and rates in consecutive patients undergoing bladder outlet surgery without
augmentation for neurogenic urinary incontinence. METHODS: From 2000 to 2007, 37
patients underwent bladder neck sling (BNS), and from 2007 to 2013, 45 patients
had Leadbetter/Mitchell bladder neck revision plus sling (LMS), all without
augmentation. Mitrofanoff channels were created in all cases. Twenty children
with persistent outlet insufficiency underwent bladder neck closure (BNC). All
patients had pre- and postoperative urodynamic testing (UD). RESULTS: Mean follow
up was 60 months after BNS, 38 months after LMS, and 29 months after BNC.
Continence (dry, no pads) was achieved significantly more often with LMS versus
BNS (66% vs. 37%). There were no significant differences between these patients
in preoperative UD % capacity, end filling pressure (EFP), or compliance. Those
that became dry had a greater % capacity on postoperative UD, but postoperative
EFP was similar between dry and wet LMS and BNS patients. BNC resulted in dryness
in 65% of patients, with most incontinence occurring from the Mitrofanoff stoma
associated with filling pressures > 40 cm. A total of 10 (12%) children had
augmentation, seven after BNC. Clinical indications were end filling pressures >
40 cm plus hydronephrosis >= grade 3, and/or persistent incontinence. Need for
augmentation was not predicted by preoperative urodynamic parameters.
Postoperative UD in those who were augmented showed significantly less % capacity
and compliance, and significantly greater EFP, than those not augmented.
CONCLUSIONS: Dryness was achieved in only 33% of BNS versus 66% of LMS and BNC
patients. Twelve percent of consecutive children undergoing bladder outlet
surgery for neurogenic incontinence developed clinical parameters leading to
augmentation. These occurred most often after BNC.
PMID- 26429599
TI - Statistical interpretation, Re: "Further analysis of the Glans-Urethral Meatus
Shaft (GMS) hypospadias score: Correlation with postoperative complications".
PMID- 26429600
TI - Characteristics of sleep apnea in infants with Pierre-Robin sequence: Is there
improvement with advancing age?
AB - OBJECTIVES: To investigate changes in obstructive sleep apnea (OSA) and central
sleep apnea (CSA) in infants with Pierre-Robin sequence (PRS) with advancing age
and after mandibular distraction osteogenesis (MDO). METHODS: Charts from 141
infants with PRS that presented to our tertiary-care children's hospital between
2005 and 2015 were retrospectively reviewed. Forty-five patients received a
polysomnogram (PSG) prior to surgical intervention. Linear regression was
utilized to compare age at pre-operative PSG with apnea-hypopnea index (AHI),
obstructive apnea-hypopnea index (OAHI), and central apnea index (CAI). We then
analyzed a subset of 9 patients who underwent MDO with pre- and post-operative
PSGs. Wilcoxon signed-rank test was utilized to examine differences in pre- and
post-operative OSA and CSA scores. RESULTS: Forty-five patients received pre
operative PSGs. Of these, 80.0% demonstrated severe sleep apnea (AHI>=10), 68.9%
demonstrated severe obstructive sleep apnea (OAHI>=10), and 55.6% demonstrated
central sleep apnea (CAI>=1). There was no significant pattern of decrease in
AHI, OAHI, and CAI with increased age up to 1 year. Among the 9 patients who
underwent MDO with pre- and post-operative PSGs, significant reductions in AHI,
OAHI, CAI, and percentage of total sleep time with arterial oxygen saturation
(SaO2) <90% and significant increases in SaO2 nadir were identified after MDO.
CONCLUSIONS: Contrary to previously examined literature in non-PRS patients, we
did not find a decreased severity of central or obstructive sleep apnea with
advancing age. Infants with PRS who underwent MDO demonstrated significant
decreases in both obstructive and central apnea indices.
PMID- 26429601
TI - Follow-up audiometry after bilateral myringotomy and tympanostomy tube insertion.
AB - OBJECTIVE: There are no evidence-based guidelines regarding timing of
postoperative audiometric follow-up for children undergoing tympanostomy tube
insertion. Given the variability of follow-up among physicians, we attempt to
guide the timing of postoperative audiograms using objective data. STUDY DESIGN:
Retrospective chart review. METHODS: All pediatric patients undergoing primary
bilateral myringotomy and tympanostomy tube insertion for otitis media with
effusion who had audiometric data available at two follow-up times were
identified from 2014. Patients were classified according to the type of
audiometry performed and were further categorized into those who had tympanostomy
tube insertion only and those who had concurrent adenotonsillectomies. RESULTS:
34 patients were included in the study. Among patients assessed by sound field
audiometry, the mean sound field threshold value was 29.2dB preoperatively and
improved to 21dB 2 weeks postoperatively and 17.9dB 6 to 10 weeks
postoperatively. The difference between the two postoperative means was
significant (p<0.0001). For patients evaluated by pure-tone audiometry, the mean
preoperative air-bone gap was 20.1dB; this improved to 10dB at the first
postoperative visit and 7.3dB at the second visit. The difference between the two
means was significant (p<0.0001). For the subgroups in which adjunct
adenotonsillectomy was performed, the greater improvement at the later follow-up
was still statistically significant. CONCLUSIONS: Progressive hearing improvement
was demonstrated from 2 weeks to 6 to 10 weeks postoperatively. We recommend
testing no fewer than 6 weeks after tympanostomy tube insertion. Earlier
audiometry underestimates the degree of hearing improvement.
PMID- 26429602
TI - Management of the critical airway when an EXIT procedure is not an option: A case
report.
AB - Perinatal imaging facilitates detection of congenital head and neck masses to
plan fetal procedures which secure the airway. Ex utero intrapartum therapy
(EXIT) procedures are preferred to protect the neonatal airway. Herein we present
a case in which a neonate with a large oropharyngeal lymphovascular malformation
was delivered and the airway successfully managed without an EXIT procedure using
a multidisciplinary approach. Preparations for the non-EXIT delivery and critical
airway management are described.
PMID- 26429603
TI - Epigenetic markers for newborn congenital heart defect (CHD).
AB - OBJECTIVE: Our objective was to determine whether there were significant
differences in genome-wide DNA methylation in newborns with major congenital
heart defect (CHD) compared to controls. We also evaluated methylation of
cytosines in CpG motifs for the detection of these CHDs. METHODS: Genome-wide DNA
methylation analysis was performed on DNA from 60 newborns with various CHDs,
including hypoplastic left heart syndrome, ventricular septal deficit, atrial
septal defect, pulmonary stenosis, coarctation of the aorta and Tetralogy of
Fallot, and 32 controls. RESULTS: Highly significant differences in cytosine
methylation were seen in a large number of genes throughout the genome for all
CHD categories. Gene ontology analysis of CHD overall indicated over-represented
biological processes involving cell development and differentiation, and
anatomical structure morphogenesis. Methylation of individual cytosines in CpG
motifs had high diagnostic accuracy for the detection of CHD. For example, for
coarctation one predictive model based on levels of particular cytosine
nucleotides achieved a sensitivity of 100% and specificity of 93.8% (AUC = 0.974,
p < 0.00001). CONCLUSION: Profound differences in cytosine methylation were
observed in hundreds of genes in newborns with different types of CHD. There
appears to be the potential for development of accurate genetic biomarkers for
CHD detection in newborns.
PMID- 26429604
TI - Conjugated Polyelectrolyte-Induced Self-Assembly of Alkynylplatinum(II) 2,6
Bis(benzimidazol-2'-yl)pyridine Complexes.
AB - Water-soluble cationic alkynylplatinum(II) 2,6-bis(benzimidazol-2'-yl)pyridine
(bzimpy) complexes have been demonstrated to undergo supramolecular assembly with
anionic polyelectrolytes in aqueous buffer solution. Metal-metal-to-ligand charge
transfer (MMLCT) absorptions and triplet MMLCT ((3) MMLCT) emissions have been
found in UV/Vis absorption and emission spectra of the electrostatic assembly of
the complexes with non-conjugated polyelectrolytes, driven by Pt???Pt and pi-pi
interactions among the complex molecules. Interestingly, the two-component
ensemble formed by [Pt(bzimpy-Et){C?CC6 H4 (CH2 NMe3 -4)}]Cl2 (1) with para
linked conjugated polyelectrolyte (CPE), PPE-SO3 (-) , shows significantly
different photophysical properties from that of the ensemble formed by 1 with
meta-linked CPE, mPPE-Ala. The helical conformation of mPPE-Ala allows the
formation of strong mPPE-Ala-1 aggregates with Pt???Pt, electrostatic, and pi-pi
interactions, as revealed by the large Stern-Volmer constant at low
concentrations of 1. Together with the reasonably large Forster radius, large
HOMO-LUMO gap and high triplet state energy of mPPE-Ala to minimize both photo
induced charge transfer (PCT) and Dexter triplet energy back-transfer (TEBT)
quenching of the emission of 1, efficient Forster resonance energy transfer
(FRET) from mPPE-Ala to aggregated 1 molecules and strong (3) MMLCT emission have
been found, while the less strong PPE-SO3 (-) -1 aggregates and probably more
efficient PCT and Dexter TEBT quenching would account for the lack of (3) MMLCT
emission in the PPE-SO3 (-) -1 ensemble.
PMID- 26429605
TI - Vancomycin Tissue Pharmacokinetics in Patients with Lower-Limb Infections via In
Vivo Microdialysis.
AB - BACKGROUND: Vancomycin is a common treatment option for skin and skin structure
infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Given
the increasing prevalence of MRSA, vancomycin is widely used as empirical
therapy. In patients with lower-limb infections, antimicrobial penetration is
often reduced because of decreased vascular perfusion. In this study, we
evaluated the tissue concentrations of vancomycin in hospitalized patients with
lower-limb infections. METHODS: An in vivo microdialysis catheter was inserted
near the margin of the wound and was perfused with lactated Ringer's solution.
Tissue and serum samples were obtained after steady state for one dosing
interval. Tissue concentrations were corrected for percentage of in vivo recovery
using the retrodialysis technique. RESULTS: Nine patients were enrolled (mean +/-
SD: age, 54 +/- 19 years; weight, 105.6 +/- 31.5 kg). Patients received a mean of
12.8 mg/kg of vancomycin every 12 hours (n = 7), every 8 hours (n = 1), or every
24 hours (n = 1). Mean +/- SD steady-state trough vancomycin concentrations in
serum and tissue were 11.1 +/- 3.3 and 6.0 +/- 2.6 MUg/mL. The mean +/- SD 24
hour free drug areas under the curve for serum and wound were 283.7 +/- 89.4 and
232.8 +/- 75.7 MUg*h/mL, respectively. The mean +/- SD tissue penetration ratio
was 0.8 +/- 0.2. CONCLUSIONS: These data suggest that against MRSA with minimum
inhibitory concentrations of 1 MUg/mL or less, vancomycin achieved blood
pharmacodynamic targets required for the likelihood of success. Reduced
concentrations may contribute to poor outcomes and the development of resistance.
As other literature suggests, alternative agents may be needed when the pathogen
of interest has a minimum inhibitory concentration greater than 1 MUg/mL.
PMID- 26429606
TI - Plate Fixation of Proximal Fifth Metatarsal Fracture.
AB - BACKGROUND: Intramedullary screw fixation of fractures of the proximal fifth
metatarsal bone may not be satisfactory in comminuted fractures or when the
lateral metatarsal bowing has to be restored. We report our experience with plate
fixation in these circumstances. METHODS: Between June 1, 2009, and January 31,
2013, 13 patients who had comminuted fracture or nonunion of fracture of the
proximal fifth metatarsal bone underwent plate fixation. Study patients were
followed up for a mean of 500 days (range, 51-1238 days). Their medical records
and radiographs were retrospectively reviewed for demographic and operative data
and radiologic evidence of fracture healing. At their most recent follow-up,
patients were evaluated for pain levels with a visual analog scale, for foot
function with the Foot and Ankle Disability Index, and for quality of life with
the 12-Item Short-Form Health Survey. RESULTS: Fracture union was evident in 12
patients after a mean of 56.8 days (range, 30-92 days). There was only one major
complication of sural nerve neuroma and reflex sympathetic dystrophy. Four
patients required reoperation for plate removal. Plate fixation of proximal fifth
metatarsal comminuted fractures is associated with high union rates, relief of
pain, and patient satisfaction. However, plate removal for various reasons was
required in approximately one-third of the study patients. This high revision
rate might be avoided by better selection of patients and meticulous
intraoperative identification and preservation of the sural nerve. CONCLUSIONS:
We recommend reserving plate fixation for proximal fifth metatarsal fractures for
cases of laterally bowed fifth metatarsal or comminuted fractures.
PMID- 26429607
TI - Candida albicans Immunotherapy for Verrucae Plantaris.
AB - BACKGROUND: Verrucae plantaris is a viral disease caused by human papilloma virus
that is commonly seen in the office setting and is often challenging to treat
owing to its high recurrence rate and recalcitrant profile. Candida albicans
intralesional injections have been hypothesized to incite an immunogenic response
toward the virus. METHODS: We report on the immunotherapeutic effect of
intralesional injection of C albicans into plantar verrucae with a retrospective
medical record analysis of 80 patients. Using a luer-lock syringe, 0.1 to 0.3 mL
of C albicans antigen was injected into either the first known lesion or the
largest lesion. RESULTS: The success rate of intralesional C albicans, defined as
total clearance of the lesion, was 65%, which may be underestimated because
patients lost to follow-up were included in the 35% failure rate. It was also
found that female patients with a previous tissue-destructive treatment process
were more than four times more likely to respond to C albicans therapy, whereas
this effect was less pronounced in the male patient population. CONCLUSIONS:
These results indicate that a series of intralesional injections of C albicans is
an effective and efficient method of treatment for verrucae plantaris.
PMID- 26429608
TI - Reduction in Size and Number of Plantar Verrucae in Human Immunodeficiency Virus
Infected Individuals After the Implementation of Highly Active Antiretroviral
Therapy.
AB - BACKGROUND: Implementation of highly active antiretroviral therapy (HAART)
significantly increased the life expectancy of those living with human
immunodeficiency virus (HIV). Except for prevalence, scientific reports regarding
clinical manifestations of plantar verrucae in the post-HAART era are lacking.
The objective of this study was to compare clinical manifestations of plantar
verrucae between HIV-infected and noninfected individuals and then to compare
these findings with those observed before the implementation of HAART. METHODS:
Nineteen patients with plantar verrucae (ten with HIV and nine without HIV) were
examined to determine the size, number, and clinical type of verrucae present.
The two groups were first compared with each other and then with previously
collected data from a similar analysis conducted in 1995, before the
implementation of HAART. Statistical significance was determined using the Fisher
exact test or the Wilcoxon rank sum test. RESULTS: No significant differences
were observed in the size, number, or clinical type of verrucae between HIV
negative and HIV-positive patients. Compared with the 1995 data, there was a
significant decrease in the number of verrucae lesions per individual and a
nonsignificant decrease in the average size of verrucae in HIV-positive patients.
CONCLUSIONS: Study results indicate that the implementation of HAART has impacted
the clinical manifestations of plantar verrucae in HIV-positive individuals.
Further analyses with a larger number of patients are required to confirm and
substantiate these findings.
PMID- 26429609
TI - Efinaconazole Topical Solution, 10% Efficacy in Patients with Onychomycosis and
Coexisting Tinea Pedis.
AB - BACKGROUND: We sought to evaluate the efficacy of efinaconazole topical solution,
10%, in patients with onychomycosis and coexisting tinea pedis. METHODS: We
analyzed 1,655 patients, aged 18 to 70 years, randomized (3:1) to receive
efinaconazole topical solution, 10%, or vehicle from two identical multicenter,
double-blind, vehicle-controlled 48-week studies evaluating safety and efficacy.
The primary end point was complete cure rate (0% clinical involvement of the
target toenail and negative potassium hydroxide examination and fungal culture
findings) at week 52. Three groups were compared: patients with onychomycosis and
coexisting interdigital tinea pedis on-study (treated or left untreated) and
those with no coexisting tinea pedis. RESULTS: Treatment with efinaconazole
topical solution, 10%, was significantly more effective than vehicle use
irrespective of the coexistence of tinea pedis or its treatment. Overall, 352
patients with onychomycosis (21.3%) had coexisting interdigital tinea pedis, with
215 of these patients (61.1%) receiving investigator-approved topical antifungal
agents for their tinea pedis in addition to their randomized onychomycosis
treatment. At week 52, efinaconazole complete cure rates of 29.4% were reported
in patients with onychomycosis when coexisting tinea pedis was treated compared
with 16.1% when coexisting tinea pedis was not treated. Both cure rates were
significant compared with vehicle (P = .003 and .045, respectively), and in the
latter subgroup, no patients treated with vehicle achieved a complete cure.
CONCLUSIONS: Treatment of coexisting tinea pedis in patients with onychomycosis
enhances the efficacy of once-daily topical treatment with efinaconazole topical
solution, 10%.
PMID- 26429610
TI - Static Foot Posture and Mobility Associated With Postural Sway in Elderly Women
Using a Three-dimensional Foot Scanner.
AB - BACKGROUND: Maintaining balance is a complex phenomenon that is influenced by a
range of sensorimotor factors. Foot posture and mobility may also influence
balance and postural sway. Recently, three-dimensional foot scanners have been
used to assess foot posture. This tool allows many individuals to be scanned
quickly and easily and helps eliminate patients' radiation exposure. The
objective of this study was to determine whether static foot posture and mobility
are independently associated with postural sway in a large community sample of
older women using objective measures of balance status and the recently launched
technology of three-dimensional foot scanning. METHODS: This cross-sectional
study included 140 community-dwelling elderly women (mean +/- SD age, 73.9 +/-
5.1 years) recruited in Kasama City, Japan. The postural sway variables were
total path length and area and were measured by force plate. We measured static
foot posture, sitting and standing navicular height, and mobility using a three
dimensional foot scanner. Foot mobility was determined as the amount of vertical
navicular excursion between the positions of the subtalar joint, from neutral in
sitting position to relaxed bilateral standing. RESULTS: After adjusting for
potential cofounders, analysis of covariance revealed that sitting navicular
height was associated with total path length (P = .038) and area (P = .031). Foot
mobility was associated with total path length (P = .018). CONCLUSIONS: These
findings suggest that sitting navicular height and foot mobility are associated
with postural sway in elderly women and might be an important factor in defining
balance control in older adults.
PMID- 26429611
TI - Medical and Economic Impact of a Free Student-Run Podiatric Medical Clinic A
Preliminary Analysis.
AB - BACKGROUND: Data from the free student-run podiatric medical clinic at Clinica
Tepati at the University of California, Davis, were used to analyze medical and
economic impacts on health-care delivery and to extrapolate the economic impact
to the national level. Clinica Tepati also provides an excellent teaching
environment and services to the uninsured Hispanic population in the Greater
Sacramento area. METHODS: In this analysis, we retrospectively reviewed patient
medical records for podiatric medical encounters during 15 clinic days between
November 2010 and February 2012. The economic impact was evaluated by matching
diagnoses and treatments with Medicare reimbursement rates using International
Classification of Diseases codes, Current Procedural Terminology codes, and the
prevailing Medicare reimbursement rates. RESULTS: Sixty-three podiatric medical
patients made 101 visits during this period. Twenty patients returned to the
clinic for at least one follow-up visit or for a new medical concern. Thirty-nine
different diagnoses were identified, and treatments were provided for all 101
patient encounters/visits. Treatments were limited to those within the clinic's
resources. This analysis estimates that $17,332.13 worth of services were
rendered during this period. CONCLUSIONS: These results suggest that the free
student-run podiatric medical clinic at Clinica Tepati had a significant medical
and economic impact on the delivery of health care at the regional level, and
when extrapolated, nationally as well. These student-run clinics also play an
important role in medical education settings.
PMID- 26429612
TI - A Mobile Health Service to Manage Diabetic Foot in Homeless Patients.
AB - BACKGROUND: Homeless people live in poverty, with limited access to public health
services. They are likely to experience chronic medical conditions, such as
diabetes mellitus; however, they do not always receive the necessary services to
prevent complications. This study was designed to determine the effectiveness of
a volunteer health service outreach to reduce disparity in diabetic foot care for
homeless people. METHODS: The research was conducted on 21 patients with diabetic
ulcers of 930 homeless people visited between 2008 and 2013. Each ulcer was
treated with regular medication every week for a mean +/- SD of 17.6 +/- 12
months. The inclusion criteria were 1) homeless with a previous diagnosis of
diabetes or a blood glucose level greater than 126 mg/dL at first check and 2)
foot ulcer caused by diabetic vasculopathy or neuropathy. The efficacy of the
interventions was assessed against the number of successfully cured diabetic feet
based on a reduced initial Wagner classification score for each ulcer. RESULTS:
Clinical improvement was observed in 18 patients (86%), whose pathologic
condition was completely resolved after 3 years and, therefore, no longer needed
medication. One patient died of septic shock and kidney failure, and two patients
needed amputation owing to clinical worsening of ulcers (Wagner class 4 at the
last visit). CONCLUSIONS: Most homeless people who have diabetes and diabetic
foot encounter many difficulties managing their disease, and a volunteer health
care unit could be a suitable option to bridge these gaps.
PMID- 26429613
TI - Perceived Stress and Coffee and Energy Drink Consumption Predict Poor Sleep
Quality in Podiatric Medical Students A Cross-sectional Study.
AB - BACKGROUND: A cross-sectional survey administered to first- and second-year
podiatric medical students aimed to investigate the effect of coffee intake,
energy drink consumption, and perceived stress on sleep quality in medical
students during their preclinical studies. METHODS: Ninety-eight of 183 students
contacted (53.6%) completed a questionnaire comprising standard instruments
measuring sleep quality (Pittsburgh Sleep Quality Index), daytime sleepiness
(Epworth Sleepiness scale), and perceived stress (ten-item Perceived Stress
Scale). Furthermore, we investigated coffee and energy drink consumption.
Logistic regression was conducted to identify factors associated with poor sleep
quality and the relation between sleep quality and academic performance (grade
point average). RESULTS: High prevalences of poor sleep quality, excessive
daytime sleepiness, and perceived stress were reported. In addition, higher odds
of developing poor sleep quality were associated with coffee and energy drink
intake, perceived stress, and excessive daytime sleepiness. The total Pittsburgh
Sleep Quality Index score was inversely correlated with grade point average.
CONCLUSIONS: First- and second-year podiatric medical students have poor sleep
quality. Further research is needed to identify effective strategies to reduce
stress and decrease coffee and energy drink intake to minimize their negative
effect on sleep quality and academic performance in podiatric medical students.
PMID- 26429614
TI - Pediatric Subtalar Joint Synovial Chondromatosis Report of a Case and an Up-to
date Review.
AB - Synovial chondromatosis is a rare, usually benign disorder affecting the
population predominantly in the third and fourth decades of life and mainly
involving the large weightbearing joints of the lower limb-the knees and the hip.
In this report, we highlight an unusual pediatric clinical presentation of
synovial osteochondromatosis involving the subtalar joint and discuss its
surgical management; we also provide a comprehensive up-to-date literature review
of the disorder. This patient was successfully treated with en masse surgical
excision. He has been doing well, with complete pain relief and improved range of
motion at 1-year follow-up. An exceptional involvement of the subtalar joint and
an unusual presentation in the pediatric age group makes this case unique.
PMID- 26429615
TI - A Novel Case of an Acrochordon Occurring on the Plantar Foot.
AB - We report on a 63-year-old male who was found to have an acrochordon on his
plantar foot. Although acrochordons constitute a common benign clinical finding,
this observation represents, to our knowledge, only the second case reported on
the foot and the first occuring on the plantar surface.
PMID- 26429616
TI - True Pathologic Abnormality versus Artifact Foot Position and Magic Angle
Artifact in the Peroneal Tendons with 3T Imaging.
AB - Magnetic resonance imaging is a commonly ordered examination by many foot and
ankle surgeons for ankle pain and suspected peroneal tendon pathologic
abnormalities. Magic angle artifact is one of the complexities associated with
this imaging modality. Magic angle refers to the increased signal on magnetic
resonance images associated with the highly organized collagen fibers in tendons
and ligaments when they are orientated at a 55 degrees angle to the main
magnetic field. We present several examples from a clinical practice setting
using 3T imaging illustrating a substantial reduction in magic angle artifact of
the peroneal tendon in the prone plantarflexed position compared with the
standard neutral (right angle) position.
PMID- 26429618
TI - Evidence-Based Approach to Advanced Wound Care Products.
AB - There is increasing pressure from industry to use advanced wound care products
and technologies. Many are very expensive but promise to reduce overall costs
associated with wound care. Compelling anecdotal evidence is provided that
inevitably shows wounds that failed all other treatments but responded positively
to the subject product. Evidence-based medicine is the standard by which
physician-scientists must make their clinical care decisions. In an attempt to
provide policy makers with the most current evidence on advanced wound care
products, the Department of Veteran Affairs conducted an Evidence-based Synthesis
Program review of advanced wound care products. This paper suggests how to take
this information and apply it to policy to drive evidence-based care to improve
outcomes and fiduciary responsibility.
PMID- 26429617
TI - Kyrle Disease A Rare Dermatologic Condition Associated with the Diabetic Foot.
AB - We report two cases of biopsy-confirmed Kyrle disease. Kyrle disease is one of
the perforating dermatoses associated with diabetic patients undergoing renal
dialysis. In this report, we describe the clinical and histopathologic features,
the differential diagnoses, and successful treatment of this unusual disorder.
PMID- 26429619
TI - Our APMA.
PMID- 26429625
TI - Effect of concurrent walking and interlocutor distance on conversational speech
intensity and rate in Parkinson's disease.
AB - Previous studies have demonstrated a negative effect of concurrent walking and
talking on gait in Parkinson's disease (PD) but there is limited information
about the effect of concurrent walking on speech production. The present study
examined the effect of sitting, standing, and three concurrent walking tasks
(slow, normal, fast) on conversational speech intensity and speech rate in
fifteen individuals with hypophonia related to idiopathic Parkinson's disease
(PD) and fourteen age-equivalent controls. Interlocuter (talker-to-talker)
distance effects and walking speed were also examined. Concurrent walking was
found to produce a significant increase in speech intensity, relative to standing
and sitting, in both the control and PD groups. Faster walking produced
significantly greater speech intensity than slower walking. Concurrent walking
had no effect on speech rate. Concurrent walking and talking produced significant
reductions in walking speed in both the control and PD groups. In general, the
results of the present study indicate that concurrent walking tasks and the speed
of concurrent walking can have a significant positive effect on conversational
speech intensity. These positive, "energizing" effects need to be given
consideration in future attempts to develop a comprehensive model of speech
intensity regulation and they may have important implications for the development
of new evaluation and treatment procedures for individuals with hypophonia
related to PD.
PMID- 26429626
TI - Characteristics of innate lymphoid cells (ILCs) and their role in immunological
disorders (an update).
AB - Innate lymphoid cells (ILCs) are a novel family of hematopoietic effectors and
regulators of innate immunity. Although these cells are morphologically similar
to B cells and T cells, however they do not express antigen receptors. ILCs seems
to have emerging roles in innate immune responses against infectious or non
infectious microorganisms, protection of the epithelial barrier, lymphoid
organogenesis and inflammation, tissue remodeling and regulating homeostasis of
tissue stromal cells. In addition, it has recently been reported that ILCs have a
crucial role in several disorders such as allergy and autoimmunity. Based on
their phenotype and functions, ILCs are classified into three major groups called
ILCs1, ILCs2, and ILCs3. Here we reviewed the most recent data concerning diverse
ILC phenotypes, subclasses, functions in immune responses as well as in immune
mediated disorders.
PMID- 26429627
TI - Rationalizing thymic selection for functional T-cells: A commentary.
AB - What are the minimum specificity requirements of a thymic selective process that
establishes (1) restrictive recognition of peptide, (2) the Self (S)-Nonself (NS)
discrimination, and (3) the categories of effector function? Given an answer to
that question, how well does it fit with the observed selective processes in
thymus where T-cells are generated? Any discrepancies between the two must be
rationalized. The goal of this essay is to attempt just that.
PMID- 26429628
TI - Carcinogenicity of glycidamide in B6C3F1 mice and F344/N rats from a two-year
drinking water exposure.
AB - Acrylamide is a contaminant in baked and fried starchy foods, roasted coffee, and
cigarette smoke. Previously we reported that acrylamide is a multi-organ
carcinogen in B6C3F1 mice and F344/N rats, and hypothesized that acrylamide is
activated to an ultimate carcinogen through metabolism to the epoxide
glycidamide. We have now examined the carcinogenic effects of glycidamide
administered at 0, 0.0875, 0.175, 0.35 and 0.70 mM in drinking water to the same
strains of rodents for two years. In male and female mice, there were significant
increases in tumors of the Harderian gland, lung, forestomach, and skin. Female
mice also had an increased incidence of tumors of the mammary gland and ovary. In
male and female rats, there were significant increases in thyroid gland and oral
cavity neoplasms and mononuclear cell leukemia. Male rats also had increases in
tumors of the epididymis/testes and heart, while female rats demonstrated
increases in tumors of the mammary gland, clitoral gland, and forestomach. A
similar spectrum of tumors was obtained in mice and rats administered acrylamide.
These data indicate that, under the conditions of these bioassays, acrylamide is
efficiently metabolized to glycidamide and that the carcinogenic activity of
acrylamide is due to its conversion into glycidamide.
PMID- 26429629
TI - The absorption and metabolism of a single L-menthol oral versus skin
administration: Effects on thermogenesis and metabolic rate.
AB - We investigated the absorption and metabolism pharmacokinetics of a single L
menthol oral versus skin administration and the effects on human thermogenesis
and metabolic rate. Twenty healthy adults were randomly distributed into oral
(capsule) and skin (gel) groups and treated with 10 mg kg(-1) L-menthol
(ORALMENT; SKINMENT) or control (lactose capsule: ORALCON; water application:
SKINCON) in a random order on two different days. Levels of serum L-menthol
increased similarly in ORALMENT and SKINMENT (p > 0.05). L-menthol
glucuronidation was greater in ORALMENT than SKINMENT (p < 0.05). Cutaneous
vasoconstriction, rectal temperature and body heat storage showed greater
increase following SKINMENT compared to ORALMENT and control conditions (p <
0.05). Metabolic rate increased from baseline by 18% in SKINMENT and 10% in
ORALMENT and respiratory exchange ratio decreased more in ORALMENT (5.4%) than
SKINMENT (4.8%) compared to control conditions (p < 0.05). Levels of plasma
adiponectin and leptin as well as heart rate variability were similar to control
following either treatment (p > 0.05). Participants reported no cold, shivering,
discomfort, stress or skin irritation. We conclude that a single L-menthol skin
administration increased thermogenesis and metabolic rate in humans. These
effects are minor following L-menthol oral administration probably due to faster
glucuronidation and greater blood menthol glucuronide levels.
PMID- 26429630
TI - Foundational perspectives on causality in large-scale brain networks.
AB - A profusion of recent work in cognitive neuroscience has been concerned with the
endeavor to uncover causal influences in large-scale brain networks. However,
despite the fact that many papers give a nod to the important theoretical
challenges posed by the concept of causality, this explosion of research has
generally not been accompanied by a rigorous conceptual analysis of the nature of
causality in the brain. This review provides both a descriptive and prescriptive
account of the nature of causality as found within and between large-scale brain
networks. In short, it seeks to clarify the concept of causality in large-scale
brain networks both philosophically and scientifically. This is accomplished by
briefly reviewing the rich philosophical history of work on causality, especially
focusing on contributions by David Hume, Immanuel Kant, Bertrand Russell, and
Christopher Hitchcock. We go on to discuss the impact that various
interpretations of modern physics have had on our understanding of causality.
Throughout all this, a central focus is the distinction between theories of
deterministic causality (DC), whereby causes uniquely determine their effects,
and probabilistic causality (PC), whereby causes change the probability of
occurrence of their effects. We argue that, given the topological complexity of
its large-scale connectivity, the brain should be considered as a complex system
and its causal influences treated as probabilistic in nature. We conclude that PC
is well suited for explaining causality in the brain for three reasons: (1) brain
causality is often mutual; (2) connectional convergence dictates that only rarely
is the activity of one neuronal population uniquely determined by another one;
and (3) the causal influences exerted between neuronal populations may not have
observable effects. A number of different techniques are currently available to
characterize causal influence in the brain. Typically, these techniques quantify
the statistical likelihood that a change in the activity of one neuronal
population affects the activity in another. We argue that these measures access
the inherently probabilistic nature of causal influences in the brain, and are
thus better suited for large-scale brain network analysis than are DC-based
measures. Our work is consistent with recent advances in the philosophical study
of probabilistic causality, which originated from inherent conceptual problems
with deterministic regularity theories. It also resonates with concepts of
stochasticity that were involved in establishing modern physics. In summary, we
argue that probabilistic causality is a conceptually appropriate foundation for
describing neural causality in the brain.
PMID- 26429631
TI - A TMS study on the contribution of visual area V5 to the perception of implied
motion in art and its appreciation.
AB - Over the last decade, researchers have sought to understand the brain mechanisms
involved in the appreciation of art. Previous studies reported an increased
activity in sensory processing regions for artworks that participants find more
appealing. Here we investigated the intriguing possibility that activity in
cortical area V5-a region in the occipital cortex mediating physical and implied
motion detection-is related not only to the generation of a sense of motion from
visual cues used in artworks, but also to the appreciation of those artworks. Art
naive participants viewed a series of paintings and quickly judged whether or not
the paintings conveyed a sense of motion, and whether or not they liked them.
Triple-pulse TMS applied over V5 while viewing the paintings significantly
decreased the perceived sense of motion, and also significantly reduced liking of
abstract (but not representational) paintings. Our data demonstrate that V5 is
involved in extracting motion information even when the objects whose motion is
implied are pictorial representations (as opposed to photographs or film frames),
and even in the absence of any figurative content. Moreover, our study suggests
that, in the case of untrained people, V5 activity plays a causal role in the
appreciation of abstract but not of representational art.
PMID- 26429632
TI - Quality assessment and antiplasmodial activity of West African Cochlospermum
species.
AB - The present study focuses on development of phytochemical methods for quality
assessment of two West-African Cochlospermum species (Cochlospermum planchonii
and Cochlospermum tinctorium) traditionally used for malaria treatment in Burkina
Faso. Antimalarial activity of preparations from dried rhizomes (decoction) was
tested against the chloroquine-sensitive Plasmodium strain 3D7 using the
histidine-rich protein II (HRP2) drug susceptibility assay and compared with
extract preparations using organic solvents of different polarity. Two main
apocarotenoids were isolated from rhizomes of C. planchonii and unambiguously
identified as dihydrocochloxanthine and cochloxanthine by spectroscopic methods.
Comparative HPLC analyses of thirty-nine (39) samples from markets and from
collections in natural habitats of both species showed a high variability in the
accumulation of cochloxanthines and related carotenoids which were proven to be
characteristic for rhizomes of both species and generally absent in leaves.
Furthermore, content of total phenolics and antioxidant activities (DPPH and
FRAP) as well as haemolytic activity of various extracts was tested. The HPLC
method presented here was validated and provides a good separation of both
compounds including 10 minor carotenoids. Extracts from both species and pure
cochloxanthine offered pronounced antioxidant activities and weak haemolytic
activity while, in contrast, dihydrocochloxanthine had a strong haemolytic effect
at the highest concentration analysed. However, cochloxanthine as well as
dihydrocochloxanthine showed erythroprotective effects against the haemolytic
activity of the reference saponin. Moderate antiplasmodial activity between 16
and 63 MUg/ml were observed with all tested extracts, and lower IC50 values were
obtained with pure dihydrocochloxanthine (IC50=6.9 MUg/ml), cochloxanthine
(IC50=6.8 MUg/ml), the DCM fraction (IC50=2.4 MUg/ml) and the ethyl acetate
fraction (IC50=11.5MUg/ml) derived from a methanolic extract of C. planchonii.
This study shows a major variability of carotenoid content and antiplasmodial
activity of both C. planchonii and C. tinctorium. The high haemolytic activity of
dihydrocochloxanthine (at 100 MUg/ml) should be considered as a selection
criterion for choosing species phenotypes for treatment.
PMID- 26429633
TI - Mortality From Malignant Melanoma in an Era of Nationwide Skin Cancer Screening.
PMID- 26429634
TI - Skin Cancer Screening in Germany. Documenting Melanoma Incidence and Mortality
From 2008 to 2013.
AB - BACKGROUND: Nationwide skin cancer screening was introduced in Germany in 2008.
The positive results of a pilot project carried out in 2003-4 in the federal
state of Schleswig-Holstein had implied that screening would lower the mortality
from melanoma. METHODS: Data on the incidence of invasive malignant melanoma of
the skin (MM; ICD-10: C43) were extracted from the databases of the Association
of Population-based Cancer Registries in Germany (GEKID) and from the Schleswig
Holstein cancer registry. Mortality rates were extracted from the official cause
of-death statistics. RESULTS: With the beginning of nationwide screening in 2008,
the age-standardized incidence rate in Germany increased by approximately 28% to
18.2 cases per 100 000 persons in 2010. In Schleswig-Holstein, the incidence fell
after the pilot project ended and has been comparable to the nationwide incidence
since 2008. For Germany overall, there has been no downward trend in MM mortality
since the introduction of nationwide screening; in 2013, the mortality rate was
2.3 deaths per 100 000 persons per year. In the area of the pilot study,
mortality declined to a level of 1.0/100 000/year until 2008 and then began to
rise again. At present, the mortality due to MM in Schleswig- Holstein is once
again the same as that in Germany overall (2.4/100 000/year). CONCLUSION: The
introduction of nationwide skin cancer screening in 2008 has not yet led to any
measurable decline in mortality due to melanoma. The current method of screening
seems to be less thorough than that used in the pilot project; this may explain
the absence of a decline in MM-related mortality in Germany overall up to the
year 2013, as well as the rising mortality in Schleswig-Holstein since the end of
the pilot program. The generation of a robust set of data on how skin cancer
screening can be optimized now seems urgently necessary.
PMID- 26429635
TI - Screening for Lung Cancer: Balancing Hope With Doubt About Applicability.
PMID- 26429637
TI - Genotyping of Toxic Pufferfish Based on Specific PCR-RFLP Products As Determined
by Liquid Chromatography/Quadrupole-Orbitrap Hybrid Mass Spectrometry.
AB - A method based on liquid chromatography-electrospray mass spectrometric analysis
of the enzymatically digested amplicons derived from the mitochondrial 16S rRNA
gene was established for the discrimination of toxic pufferfish. A MonoBis C18
narrow-bore silica monolith column (Kyoto Monotech) and a Q Exactive mass
spectrometer (Thermo Fisher) were employed for separation and detection,
respectively. Monoisotopic masses of the oligonucleotides were calculated using
Protein Deconvolution 3.0 software (Thermo Fisher). Although a lock mass standard
was not used, excellent accuracy (mass error, 0.83 ppm on average) and precision
(relative standard deviation, 0.49 ppm on average) were achieved, and a mass
accuracy of <2.8 ppm was maintained for at least 180 h without additional
calibration. The present method was applied to 29 pufferfish samples, and results
were consistent with Sanger sequencing.
PMID- 26429636
TI - Lung Cancer Screening Using Low Dose CT Scanning in Germany. Extrapolation of
results from the National Lung Screening Trial.
AB - BACKGROUND: It is now debated whether the screening of heavy smokers for lung
cancer with low dose computed tomography (low dose CT) might lower their
mortality due to lung cancer. We use data from the National Lung Screening Trial
(NLST) in the USA to predict the likely effects of such screening in Germany.
METHODS: The number of heavy smokers aged 55-74 in Germany was extrapolated from
survey data obtained by the Robert Koch Institute. Published data from the NLST
were then used to estimate the likely effects of low dose CT screening of heavy
smokers in Germany. RESULTS: If low dose CT screening were performed on 50% of
the heavy smokers in Germany aged 55-74, an estimated 1 329 506 persons would
undergo such screening. If the screening were repeated annually, then, over three
years, 916 918 screening CTs would reveal suspect lesions, and the diagnosis of
lung cancer would be confirmed thereafter in 32 826 persons. At least one
positive test result in three years would be obtained in 39.1% of the
participants (519 837 persons). 4155 deaths from lung cancer would be prevented
over 6.5 years, and the number of persons aged 55-74 who die of lung cancer in
Germany would fall by 2.6%. 12 449 persons would have at least one complication,
and 1074 persons would die in the 60 days following screening. CONCLUSION: The
screening of heavy smokers for lung cancer can lower their risk of dying of lung
cancer by 20% in relative terms, corresponding to an absolute risk reduction of
0.3 percentage points. These figures can provide the background for a critical
discussion of the putative utility of this type of screening in Germany.
PMID- 26429638
TI - Correlates of Healthy Lifestyle Beliefs and Behaviors in Parents of Overweight or
Obese Preschool Children Before and After a Cognitive Behavioral Therapy
Intervention With Text Messaging.
AB - INTRODUCTION: Significant gaps exist in the published literature regarding the
treatment of overweight/obesity in preschool-aged children, especially in primary
care settings. Parental influence plays an important factor in the development of
healthy behaviors in children, yet there is no consensus about why some behavior
change intervention strategies for parents of young children are more influential
and effective than others. OBJECTIVE: The purpose of this secondary data analysis
was to assess correlations among the study variables (healthy lifestyle beliefs,
perceived difficulty, and healthy lifestyle behaviors) in parents of
overweight/obese preschool children. A second aim explored if the parent's level
of cognitive beliefs and perceived difficulty of engaging in healthy lifestyle
behaviors correlated with text messaging cognitive behavioral support. METHODS:
Fifteen preschool-parent dyads from primary care clinics completed a 7-week
cognitive behavioral skills building intervention. Beck's Cognitive Theory guided
the intervention content, and Fogg's Behavior Model guided the implementation.
The intervention was delivered using a combination of face-to-face clinic visits
and ecological momentary interventions using text messaging. RESULTS: Supported
are the interconnected relationships among the study variables, that is, parental
healthy lifestyle beliefs, thoughts, and behaviors. At baseline, parental healthy
lifestyle belief scores significantly correlated with perceived difficulty (rs =
0.598, p < .05) and healthy lifestyle behaviors (rs = 0.545, p < .05). These
associations strengthened after the intervention. Furthermore, as parental
healthy lifestyle beliefs increased and perceived difficulty lessened, their
response rate and subsequent feedback lessened to the static text messaging
support. DISCUSSION: Findings from this study support the interconnections
between parents' thoughts, feelings, and actions toward healthy lifestyles. As
parental beliefs became stronger through cognitive behavioral skills building and
tailored text messaging, the need for general support via text messaging
lessened, warranting additional research.
PMID- 26429639
TI - Synergistic cytotoxicity against human tumor cell lines by oncolytic adenovirus
dl1520 (ONYX-015) and melphalan.
AB - AIMS AND BACKGROUND: In light of the need for more selective anticancer therapy,
much work has been directed at developing compounds or biological agents that
target functions specific to cancer cells. To this end, numerous viruses have
been engineered to exploit the dependence of cancer cells on particular anomalies
that contribute to their rogue proliferative activity, such as dysfunctional p53,
overactive mitogenic signaling, or a defective interferon response. The oncolytic
human adenovirus dl1520 (ONYX-015) was engineered to propagate specifically in
p53-deficient tumors, which comprise over half of all tumors. Based on successes
in clinical trials, the full potential of dl1520 and other oncolytic viruses may
be even better realized by using them in combination with conventional
chemotherapy drugs. METHODS: As a model system in which to test this potential,
representative cell lines from 2 common cancer types, oral squamous cell
carcinoma (HN-5a) and colon adenocarcinoma (HT-29), were chosen, as well as
platinum-drug-resistant variants of each. RESULTS: Following preliminary
screening of virus and drug combinations, dl1520 and melphalan were found to
synergistically inhibit proliferation of all the cancer cell lines. Melphalan
pretreatment or cotreatment with dl1520 enhanced inhibition of proliferation by
dl1520 by up to 60% and increased apoptosis by up to 25%. The tight-junction
protein CAR (coxsackie and adenovirus receptor), via which adenovirus enters
cells, was not upregulated by treatment with melphalan, suggesting that other
mechanisms contribute to synergy. CONCLUSIONS: The synergy between melphalan and
dl1520 suggests that tumor-selective cell killing by oncolytic viruses may be
augmented by combining with cytotoxic drugs.
PMID- 26429640
TI - Internal mammary node drainage in patients with early breast cancer.
PMID- 26429641
TI - Lactate dehydrogenase and body mass index are prognostic factors in patients with
recurrent small cell lung cancer receiving amrubicin.
AB - AIMS AND BACKGROUND: Amrubicin monotherapy can be an effective treatment option
for patients with recurrent small cell lung cancer (SCLC). We conducted this
retrospective study to investigate the prognostic factors in patients with
recurrent SCLC receiving amrubicin monotherapy. METHODS: The associations between
survival and clinical data, including the performance status, body mass index
(BMI), plasma lactate dehydrogenase (LDH) level, and plasma neuron-specific
enolase level, were evaluated in patients with recurrent SCLC, and a subset
analysis of patients with platinum-resistant disease was conducted. RESULTS: In
all, 37 patients were evaluated. The median survival from the date of initiation
of amrubicin monotherapy was 9.1 months (95% confidence interval 4.7-12.0
months). Multivariate analysis using a Cox proportional hazard model identified
the plasma LDH level (p = 0.049), BMI (p = 0.031), and platinum resistance (p =
0.032) as independent factors associated with survival. The same associations
were also observed in the subset of patients with platinum-resistant disease.
CONCLUSIONS: Our findings suggest that the plasma LDH level and BMI may be useful
prognostic factors in patients with SCLC receiving amrubicin monotherapy,
including patients with platinum-resistant disease.
PMID- 26429642
TI - Impact of aspirin on clinical outcomes for African American men with prostate
cancer undergoing radiation.
AB - AIMS AND BACKGROUND: Preclinical and clinical studies have suggested that aspirin
(ASA) may exhibit antineoplastic activity. Particularly in prostate cancer,
several reports have suggested that ASA plays a role in improved outcomes.
Therefore, we studied the role of ASA in a uniquely African American population,
which is known to harbor more aggressive and biologically different disease
compared to the general population. METHODS: We identified 289 African American
men with prostate cancer who were treated with definitive radiation therapy to a
dose of >=7560 cGy. The median follow-up was 76 months. Kaplan-Meier analysis was
used to analyze biochemical failure-free survival (bFFS), distant progression
free survival (DMPFS), and prostate cancer-specific survival (PCSS). Multivariate
Cox regression was used to analyze the impact of covariates on all endpoints.
RESULTS: There were 147 men who were ASA+ and 142 who were ASA-. The 7-year bFFS
was 80.9% for ASA+ men and 70.3% for ASA- men (p = 0.03). On multivariate
analysis, ASA use was associated with a significant reduction in biochemical
recurrences (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.34-0.93, p =
0.03). The 7-year DMPFS was 98.4% for ASA+ and 91.8% for ASA- men (p = 0.04). On
multivariate analysis, ASA use was associated with a decreased risk of distant
metastases (HR 0.23, 95% CI 0.06-0.91, p = 0.04). The 7-year PCSS was 99.3% for
ASA+ and 96.9% for ASA- men (p = 0.07). CONCLUSIONS: In this study, ASA use was
associated with improved biochemical outcomes and reduced distant metastases.
This indicates that ASA appears to play an important antineoplastic role in
African American men.
PMID- 26429643
TI - VATS lobectomy combined with limited Shaw-Paulson thoracotomy for posterolateral
Pancoast tumor.
AB - PURPOSE: Several techniques have been proposed for the challenging surgical
resection of Pancoast tumors. We describe a hybrid approach that combines video
assisted thoracic surgery (VATS) lobectomy and limited Shaw-Paulson thoracotomy.
METHODS: We report a case of Pancoast tumor in a 57-year-old man, staged as
cT3N0M0, that was treated with induction chemoradiotherapy prior to the hybrid
surgical approach. After thoracoscopic pleural cavity inspection, an upper right
VATS lobectomy by a 3-port standard approach was performed. The chest wall was
resected through a limited paravertebral incision, allowing the extraction of the
lobe together with the rib segments. The posterior chest wall defect was repaired
with a synthetic patch. RESULTS: The postoperative period was uneventful and the
pain never exceed a score of 3 on a visual analogue scale. Pathological
examination revealed nonvital tumor cells in the specimen (ypT0N0M0). The patient
is disease free at 6 months' follow-up. CONCLUSIONS: With this approach we
experienced excellent access to both the apical and hilar structures. Further
experiences are needed to validate the role of VATS lobectomy in the
multidisciplinary management of posterior Pancoast tumor.
PMID- 26429644
TI - Management of advanced pancreatic cancer in daily clinical practice.
AB - PURPOSE: The aim of this outcome study was to evaluate the management of advanced
pancreatic cancer in a real-world clinical practice; few such experiences have
been reported in the literature. METHODS: A retrospective analysis was performed
of all consecutive patients with advanced pancreatic ductal adenocarcinoma
followed at our medical oncology unit between January 2003 and December 2013.
RESULTS: We evaluated 78 patients, mostly with metastatic disease (64.1%). Median
follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median
overall survival was 8.29 months. Median age was 67 years. In univariate
analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p
= 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001)
and weight loss at diagnosis (p = 0.029) were factors that had an impact on
overall survival. In multivariate analysis, the presence of pain at onset (p =
0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed
as independent prognostic factors. CONCLUSIONS: Our data, derived from daily
clinical practice, confirmed advanced pancreatic cancer as an aggressive
malignant disease with a very short expected survival. Second-line treatment
seems to provide an advantage in terms of overall survival in patients who showed
a partial response as their best response to first-line treatment.
PMID- 26429645
TI - The key role of 18F-FDG PET/CT for correct diagnosis, staging, and treatment in a
patient with simultaneous NPC and TB lymphadenitis: case report.
AB - AIMS AND BACKGROUND: The coexistence of tuberculous lymphadenitis of the neck
region and head and neck cancer is extremely rare. In this clinical situation,
the use of positron emission and computed tomography using fluorine-18
fluorodeoxyglucose (18F-FDG PET/CT) may facilitate the differentiation between
malignancy and tuberculosis. CASE REPORT: We present a case of an Eastern
European man with nasopharyngeal cancer and concurrent tuberculous lymphadenitis.
RESULTS AND CONCLUSION: The adequate and critical interpretation of pretreatment
18F-FDG PET/CT scan addressed the multidisciplinary team to the proper staging of
disease and to the correct therapeutic approach.
PMID- 26429646
TI - Management of internal mammary nodes in early-stage breast cancer: response to
comments by De Cicco et al.
PMID- 26429647
TI - Mass-forming extramedullary hematopoiesis in multiple myeloma: 18F-FDG PET/CT is
useful in excluding extramedullary myeloma involvement.
AB - AIMS AND BACKGROUND: Extramedullary hematopoiesis (EMH), a benign condition, is
usually observed in patients with hematologic disorders. We report the first case
of mass-forming EMH detected on a 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron
emission tomography/computed tomography (PET/CT) scan in a patient with multiple
myeloma (MM). METHODS: A 58-year-old woman underwent workup for bicytopenia, and
was diagnosed with MM based on the results of bone marrow aspiration and serum
protein electrophoresis. An 18F-FDG PET/CT scan revealed a paravertebral mass
with mild FDG avidity, suggesting a tumorous condition. RESULTS: Biopsy was
performed to exclude malignancy and the mass was eventually confirmed as EMH.
CONCLUSIONS: Differential diagnosis of a mildly FDG-avid paravertebral mass in MM
should include EMH.
PMID- 26429648
TI - Misregulation of the dependence receptor DCC and its upstream lincRNA,
LOC100287225, in colorectal cancer.
AB - BACKGROUND: Long non-coding RNAs (lncRNAs), a class of regulatory RNAs, play a
major role in various cellular processes. Long intergenic non-coding RNAs
(lincRNAs), a subclass of lncRNAs, are involved in the trans- and cis-regulation
of gene expression. In the case of cis-regulation, by recruiting chromatin
modifying complexes, lincRNAs influence adjacent gene expression. METHODS: We
used quantitative real-time reverse-transcription polymerase chain reaction (qRT
PCR) to evaluate the coexpression of LOC100287225, a lincRNA, and DCC, one of its
adjacent genes that is often decreased in colorectal cancer, in pairs of tumor
and adjacent tumor-free tissues of 30 colorectal cancer patients. RESULTS: The
qRT-PCR results revealed the misregulation of these genes during tumorigenesis.
Their relative expression levels were significantly lower in tumor tissues than
adjacent tumor-free tissues. However, the analysis found no significant
correlation between reduced expression of these genes. CONCLUSIONS: Our study
demonstrated the concurrent misregulation of DCC and LOC100287225 in colorectal
cancer.
PMID- 26429649
TI - Radiotherapy for early-stage prostate cancer in men under 70 years of age.
AB - AIMS: To demonstrate that radiotherapy (RT) is a valid alternative to surgery in
men <=70 years old with localized prostate cancer. METHODS: From 1988 to 2009,
214 patients with T1-2 N0 M0 prostate cancer were treated with RT. The effects of
patient- and treatment-related risk factors on toxicity were investigated.
RESULTS: Median follow-up was 105 months (range 14.2-180). The 5-, 10-, and 15
year biochemical relapse-free survival for all 214 patients was 80%, 61.9%, and
57.5%, respectively. In bivariate analysis, age (<=65 vs 65-70 years) was not a
significant factor for biochemical relapse, while radiation dose was (p = 0.05)
in multivariate analysis. Cancer-specific survival rates at 5, 10, and 15 years
were 98.4%, 93.2%, and 69.7%, respectively. Median overall survival (OS) was 167
months (95% confidence interval 147.3-186.7). The OS rates at 5, 10, and 15 years
were 91.8%, 75.8%, and 42.5%, respectively. Acute genitourinary (GU) and
gastrointestinal (GI) toxicities occurred in 105 (49%) and 98 patients (45.8%),
respectively, with only 2 cases of grade III GI toxicity. Late GU and GI
toxicities occurred in 17 (7.9%) and 20 (9.3%) patients, respectively, with 1
grade III GI toxicity and 2 grade III GU toxicities. Risk factors for late
toxicity were age and RT dose and technique, which were unrelated to acute
toxicity. CONCLUSIONS: Age <=70 years does not consistently confer a negative
prognosis for localized prostate cancer. Radiotherapy appears to be a viable
alternative to surgery, offering excellent long-term cancer control.
PMID- 26429650
TI - Outcome of definitive and postoperative radiotherapy in patients with sinonasal
squamous cell carcinomas.
AB - AIMS: To evaluate outcomes in patients with sinonasal squamous cell carcinoma
(SCC) treated with definitive radiotherapy (DRT) and postoperative radiotherapy
(PORT). METHODS: Between 1990 and 2013, 73 patients with sinonasal SCC were
treated with radiotherapy. Fifty-two patients (71.2%) were treated with DRT and
21 (28.8%) were treated with PORT. The primary tumor sites were the maxillary
sinus in 47 patients (64.4%), the nasal cavity in 18 (24.7%), the ethmoid sinus
in 7 (9.6%), and the frontal sinus in 1 (1.4%). Four (5.4%), 11 (15.1%), 24
(32.9%), 17 (23.3%), and 17 (23.3%) patients had T1, T2, T3, T4a, and T4b tumors,
respectively. N stage was N0, N1, N2a, N2b, N2c, and N3 in 60 (82.2%), 6 (8.2%),
2 (2.7%), 2 (2.7%), and 3 (4.1%) patients, respectively. The median follow-up
period was 23 months (range 3-196). RESULTS: The 5-year local progression-free
survival (LPFS), regional progression-free survival (RPFS), distant metastasis
free survival (DMFS), and overall survival (OS) in the DRT and PORT groups were
50.6%, 82.1%, 91.1%, and 84.4% and 85.7%, 72.1%, 76.1%, and 83.5%, respectively,
without any statistically significant differences. CONCLUSIONS: The LPFS, RPFS,
DMFS, and OS were not significantly different between the DRT and PORT groups.
Given the possibility of functional disability and cosmetic disfigurement with
facial surgery, DRT might be considered as a surrogate to surgery followed by
PORT for patients with locally advanced sinonasal SCC.
PMID- 26429651
TI - Hypercholesterolemia-induced ocular disorder: Ameliorating role of phytotherapy.
AB - The ocular region is a complex structure that allows conscious light perception
and vision. It is of ecto-mesodermal origin. Cholesterol and polyunsaturated
fatty acids are involved in retinal cell function; however, hypercholesterolemia
and diabetes impair its function. Retinal damage, neovascularization, and
cataracts are the main complications of cholesterol overload. Dietary
supplementation of selected plant products can lead to the scavenging of free
reactive oxygen species, thereby protecting the ocular regions from the damage of
hypercholesterolemia. This review illustrates the dramatic effects of increased
cholesterol levels on the ocular regions. The effect of phytotherapy is discussed
in relation to the different regions of the eye, including the retina, cornea,
and lens.
PMID- 26429652
TI - Selenium status in preschool children receiving a Brazil nut-enriched diet.
AB - OBJECTIVE: The Brazilian Amazon region has selenium (Se)-rich soil, which is
associated with higher Se levels in populations fed locally grown produce. Brazil
nuts are a major source of dietary Se and are included with meals offered to
children enrolled in public preschool in Macapa. The aim of this study was to
examine Se intake and status of these children. METHODS: The Macapa group
consisted of 41 children from a public preschool who received 15 to 30 g of
Brazil nuts 3 d/wk. The control group included 88 children from the nearby city
of Belem who did not receive Brazil nut-enriched meals. In both groups, school
meals comprised >=90% of the children's total food consumption. Selenium was
assessed using hydride generation quartz tube atomic absorption spectroscopy in
plasma, erythrocytes, nails, hair and urine. Dietary intakes (macronutrients and
Se) were evaluated using the duplicate-portion method. RESULTS: Both groups
received inadequate intakes of energy and macronutrients. Selenium intake was
excessive in both groups (155.30 and 44.40 MUg/d, in Macapa and Belem,
respectively). Intake was potentially toxic in Macapa on days when Brazil nuts
were added to meals. Although biomarkers of Se exposure exceeded reference levels
in the Macapa group, no clinical symptoms of Se overload (selenosis) were
observed. CONCLUSIONS: The inclusion of Brazil nuts in school meals provided to
children with already high dietary Se intakes increased Se levels and may result
in an increased risk for toxicity. As selenosis is associated with some chronic
diseases, we recommend continued monitoring of Se intake and status in this
population.
PMID- 26429653
TI - A single FTO gene variant rs9939609 is associated with body weight evolution in a
multiethnic extremely obese population that underwent bariatric surgery.
AB - OBJECTIVES: The rs9939609 single nucleotide polymorphism (SNP) in the fat mass
and obesity-associated (FTO) gene is involved in obesity. Few studies have been
conducted on patients who underwent bariatric surgery. The aim of this study was
to evaluate the influence of FTO SNPs on body weight, body composition, and
weight regain during a 60-mo follow-up period after bariatric surgery. METHODS:
The rs9939609 was genotyped in 146 individuals using a real-time polymerase chain
reaction TaqMan assay. Data for lifestyle, comorbidities, body weight, body mass
index (BMI), excess weight loss (EWL), and body composition were obtained before
and 6, 12, 18, 24, 36, 48, and 60 mo after surgery. Data were analyzed by
comparing two groups of patients according to rs9939609 FTO gene polymorphism.
Mixed-regression models were constructed to evaluate the dynamics of body weight,
BMI, and EWL over time in female patients. RESULTS: No differences were observed
between the groups during the first 24 mo after surgery. After 36, 48, and 60 mo,
body weight, fat mass, and BMI were higher, whereas fat-free mass and EWL were
lower in the FTO-SNP patient group. Weight regain was more frequent and occurred
sooner in the FTO-SNP group. CONCLUSIONS: There is a different evolution of
weight loss in obese carriers of the FTO gene variant rs9939609 after bariatric
surgery. However, this pattern was evident at only 2 y postbariatric surgery,
inducing a lower proportion of surgery success and a greater and earlier weight
regain.
PMID- 26429654
TI - Obstructive sleep apnea is independently associated with inflammation and insulin
resistance, but not with blood pressure, plasma catecholamines, and endothelial
function in obese subjects.
AB - OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of
cardiovascular disease (CVD). Several of the proposed mechanisms for the
development of CVD in OSA are similar to those proposed for the increased risk of
CVD in obesity, so that it is difficult to determine the influence of OSA on
these pathogenic mechanisms in obese individuals. The aim of this study was to
evaluate the relationship of OSA with endothelial function, oxidative stress,
inflammatory biomarkers, metabolic profile, sympathetic nervous system activity,
and blood pressure (BP) in obese individuals. METHODS: This cross-sectional study
included 53 obese adults (28 women). Sleep study was performed with WatchPAT 200
(Itamar Medical, Caesarea, Israel) and the diagnosis of OSA was made when apnea
hypopnea index (AHI) >=5 events/h (n = 33). All participants underwent evaluation
of: body adiposity, BP, plasma catecholamines, high sensitivity C-reactive
protein (hs-CRP), adiponectin, malondialdehyde, glucose, insulin, lipid profile,
and endothelial function (EndoPAT 2000). RESULTS: In univariate analysis,
participants with OSA compared with those without OSA exhibited higher values of
neck circumference, glucose, noradrenaline, and systolic BP. After adjustment for
confounders, including adiposity, only glucose and hs-CRP were significantly
higher in OSA patients. In correlation analysis, after controlling for
confounders, AHI was positively and significantly associated with neck
circumference and hs-CRP, while minimum O2 saturation was associated negatively
and significantly with neck circumference, insulin and homeostatic model
assessment-insulin resistance (HOMA-IR). CONCLUSIONS: The present study suggests
that in obese individuals OSA is independently associated with inflammation and
insulin resistance, but not with BP, plasma catecholamines and endothelial
function.
PMID- 26429655
TI - Efficacy of zinc sulfate supplement on febrile seizure recurrence prevention in
children with normal serum zinc level: A randomised clinical trial.
AB - OBJECTIVE: Serum zinc level might be related to pathogenesis of febrile seizure
(FS). The purpose of this study was to evaluate efficacy and safety of oral zinc
supplementation on FS recurrence prevention in non-zinc-deficient children.
MATERIALS AND METHODS: In a randomized clinical study, one hundred 18 to 60 mo
old children with normal zinc level with first simple FS were referred to Shahid
Sadoughi Hospital, Yazd, Iran from May 2012 to June 2013, were randomly assigned
to two groups to receive 2 mg/kg/d zinc sulfate for six consecutive months or
placebo as control group and were followed up for 1 y for FS recurrence. RESULTS:
41 girls and 59 boys with mean age of 2.47 +/- 1.01 y were evaluated. Race, mean
weight, height and body fat were similar in both groups. FS recurrence occurred
in 19 children (38%) in the control group [95% confidence interval (CI): 19.45%
53.95%] and in 11 children (22%) in the zinc sulfate (95% CI: 57.47%-89.13%)
groups, respectively; and the zinc group had lower FS recurrence (P = 0.03). The
mean serum zinc level before intervention was lower in children with FS
recurrence (72.43 +/- 14.58 MUg/dL versus 96.33 +/- 12.69 MUg/dL, P = 0.04).
Gastrointestinal side effects (vomiting in five children, heartburn in two
children and abdominal pain in one child) were seen in 16% of the zinc group and
vomiting occurred in two children (4%) in control group and frequency of adverse
events was similar in the two groups (P = 0.1). CONCLUSION: Zinc supplementation
should be considered as effective and safe in prevention of FS recurrence.
PMID- 26429656
TI - Association between nutritional status and disease severity using the amyotrophic
lateral sclerosis (ALS) functional rating scale in ALS patients.
AB - OBJECTIVE: The nutritional status of patients with amyotrophic lateral sclerosis
(ALS) has been shown to be associated with mortality. However, there have not
been, to our knowledge, any studies on the association between nutritional status
and disease severity. The present study investigated the hypothesis that
nutritional status was negatively associated with disease severity using the ALS
functional rating scale (ALSFRS-R). METHODS: One hundred ninety-three Korean ALS
patients were divided into tertiles based on their ALSFRS-R score. Dietary intake
was measured using 24 h recall and nutritional status was determined by body mass
index (BMI) and geriatric nutritional risk index (GNRI). RESULTS: BMI and GNRI
were significantly lower in patients in the lowest tertile of ALSFRS-R. BMI and
GNRI also correlated with ALSFRS-R score, bulbar score, albumin levels, total
lymphocyte count, and total daily energy expenditure. Intakes of energy and most
nutrients were significantly lower in patients in the lowest tertiles of ALSFRS
R, but significances disappeared after adjusting for energy intake. Intakes of
vegetables, grains, seasonings, and oils were also significantly lower in
patients in the lowest tertile of ALSFRS-R. In addition, patients in the lowest
tertile of ALSFRS-R were significantly younger at disease onset, had a longer
duration of ALS, less regular exercise, and less sun exposure. CONCLUSION:
Nutritional status, as assessed by BMI and GNRI, was negatively associated with
disease severity using ALSFRS-R. The present study suggested that intake of
nutrients decreases with disease progression in ALS patients.
PMID- 26429657
TI - Should patients with ALS gain weight during their follow-up?
AB - It was recently postulated that a nutritional intervention aiming at achieving
weight gain might increase survival in ALS patients. This article discusses the
effect of nutritional status and weight gain on survival, respiratory status and
physical function. Based on the available literature, it remains unknown whether
weight gain during the progression of the disease improves survival whatever the
baseline body weight is. A high body mass index may impair respiratory muscle
function and passive mobilization of paretic patients. Future research should
evaluate the effect of changes in weight and body composition on clinical outcome
while taking into account respiratory muscle strength and physical function.
PMID- 26429658
TI - Patient Generated Subjective Global Assessment as a prognosis tool in women with
gynecologic cancer.
AB - OBJECTIVES: The aim of this study was to assess the nutritional status (NS) of
women hospitalized for gynecologic tumors and relate it to such outcomes as
hospital length of stay and 1-y mortality. METHODS: We assessed 146 women
diagnosed with gynecologic tumors who were admitted to a referral oncologic
hospital in November 2012. Data collected included medical history, duration and
reason for admission, and cases of death within 1 y. RESULTS: NS was assessed
using Patient-Generated Subjective Global Assessment (PG-SGA). The receiver
operating characteristic curve was used to define the best cutoff point for
discriminating individuals who did or did not die. We used proportional hazards
regression to assess associations between malnutrition and 1-y mortality.
According to the PG-SGA, 62.4% of the women were classified as being at
nutritional risk or having moderate or severe malnutrition. Sorting patients by
stage of cancer, there was no statistical difference in NS classification
according to the different cancer sites. The median hospital stay, in days, was
statistically lower in patients classified as well nourished. Individuals with a
score above the cutoff point of 10 were 30.7 times more likely (95% confidence
interval, 11.8-79.4) to die. There was a 52.1% rate of mortality within 1 y.
Patients classed as having some degree of malnutrition had a significantly lower
median survival rate. A diagnosis of cervical cancer and severe malnourishment
increases the likelihood of death. CONCLUSIONS: Our findings suggest that the PG
SGA can be considered not just as an indicator of nutritional risk, but also as a
major predictor of prognosis and mortality in this population.
PMID- 26429659
TI - Association between oral feeding intolerance and quality of life in acute
pancreatitis: A prospective cohort study.
AB - OBJECTIVE: Oral feeding intolerance (OFI) is a common complication of nutritional
management in acute pancreatitis (AP) and is associated with significantly worse
clinical outcomes and increased cost of treatment. However, changes in patient
reported outcomes associated with OFI during AP and effect of OFI on quality of
life (QoL) have, to our knowledge, never been studied. The aim of this study was
to investigate the relationship between OFI and QoL in patients with AP. METHODS:
We conducted a prospective cohort study of patients with AP. Patients were
grouped according to whether they developed OFI during hospitalization. QoL was
recorded daily during hospitalization and at 1 and 4 wk after discharge. One-way
analysis of covariance and repeated measures analysis were conducted. P < 0.05
was accepted as statistically significant. RESULTS: The study included 131
patients with AP. Fifty-two (40%) developed OFI during hospitalization. Overall
QoL was significantly impaired in the OFI group (mean difference = -16.1; 95%
confidence interval, -24.4 to -7.8; P <= 0.001). Five individual domains-physical
limitations, psychological function, sleep, pain, and visceral function-were
significantly impaired in the OFI group during hospitalization. Overall QoL
improved significantly within each group from hospitalization to follow-up (P <
0.001) with no significant difference between the two groups at follow-up (mean
difference = -2; 95% confidence interval, -7.1 to 3.2; P = 0.449). CONCLUSIONS:
QoL is significantly impaired in patients with AP who develop OFI. Nutritional
management of acute pancreatitis needs to be optimized to prevent the occurrence
of OFI.
PMID- 26429660
TI - Association of nutritional risk and adverse medical outcomes across different
medical inpatient populations.
AB - OBJECTIVE: The aim of this study was to examine the prevalence of nutritional
risk and its association with multiple adverse clinical outcomes in a large
cohort of acutely ill medical inpatients from a Swiss tertiary care hospital.
METHODS: We prospectively followed consecutive adult medical inpatients for 30 d.
Multivariate regression models were used to investigate the association of the
initial Nutritional Risk Score (NRS 2002) with mortality, impairment in
activities of daily living (Barthel Index <95 points), hospital length of stay,
hospital readmission rates, and quality of life (QoL; adapted from EQ5 D); all
parameters were measured at 30 d. RESULTS: Of 3186 patients (mean age 71 y, 44.7%
women), 887 (27.8%) were at risk for malnutrition with an NRS >=3 points. We
found strong associations (odds ratio/hazard ratio [OR/HR], 95% confidence
interval [CI]) between nutritional risk and mortality (OR/HR, 7.82; 95% CI, 6.04
10.12), impaired Barthel Index (OR/HR, 2.56; 95% CI, 2.12-3.09), time to hospital
discharge (OR/HR, 0.48; 95% CI, 0.43-0.52), hospital readmission (OR/HR, 1.46;
95% CI, 1.08-1.97), and all five dimensions of QoL measures. Associations
remained significant after adjustment for sociodemographic characteristics,
comorbidities, and medical diagnoses. Results were robust in subgroup analysis
with evidence of effect modification (P for interaction < 0.05) based on age and
main diagnosis groups. CONCLUSION: Nutritional risk is significant in acutely ill
medical inpatients and is associated with increased medical resource use, adverse
clinical outcomes, and impairments in functional ability and QoL. Randomized
trials are needed to evaluate evidence-based preventive and treatment strategies
focusing on nutritional factors to improve outcomes in these high-risk patients.
PMID- 26429661
TI - Association between basal metabolic function and bone metabolism in
postmenopausal women with type 2 diabetes.
AB - OBJECTIVE: Diabetes is a risk factor for osteoporosis, and glycemic control is
critical during osteoporosis treatment in patients with type 2 diabetes (T2D).
However, diabetic therapies have potentially adverse effects on bone metabolism.
Additionally, biomarkers for bone metabolism are directly affected by drug
therapies for osteoporosis. This study examined resting energy expenditure (REE)
and respiratory quotient (RQ) as indices of bone metabolism in postmenopausal
Japanese women with T2D. METHODS: Forty-six postmenopausal Japanese women with
T2D were examined. Procollagen type 1 N-terminal propeptide (P1NP, a fasting
serum bone formation marker) and carboxy-terminal collagen cross-links-1 (CTX-1,
a resorption marker) were evaluated, along with intact parathyroid hormone, 25
hydroxyvitamin D (25[OH]D), urine microalbumin, motor nerve conduction velocity,
sensory nerve conduction velocity, R-R interval, body composition, REE, RQ, and
bone mineral density at the nondominant distal radius. RESULTS: The mean T-score
was low with high variance (-1.7 +/- 1.6), and 18 patients (39%) met the criteria
for osteoporosis. REE was positively correlated with body mass index (beta =
0.517; r(2) = 0.250), serum calcium (beta = 0.624; r(2) = 0.200), glycated
hemoglobin A1C for the previous 6 mo (beta = 0.395; r(2) = 0.137), and the serum
P1NP/CTX-1 ratio (beta = 0.380; r(2) = 0.144). RQ was positively correlated with
serum 25(OH)D (beta = 0.387; r(2) = 0.131). CONCLUSION: The basal metabolic rate
and diabetic pathophysiology are interrelated with bone turnover.
PMID- 26429662
TI - Vitamin A exerts its antiinflammatory activities in colitis through preservation
of mitochondrial activity.
AB - OBJECTIVES: The aim of this study was to assess the protective effects of vitamin
A in a rat model of colitis to elucidate a possible mechanism of action. METHODS:
Male rats were fed for 21 d with either a normal diet or high vitamin A diet
(5000 IU/d). On day 22, colitis was induced with 2,4,6-trinitrobenzenesulfonic
acid (TNBS). Rats were sacrificed after 24 h and colonic tissue was removed for
evaluation. RESULTS: Morphologically, in the supplemented group preservation of
tissue architecture, no vasculitis or necroses were detected. Biochemically,
decreased myeloperoxidase activity and protection of the mitochondria as
evaluated by preserving tissue oxygen consumption, mitochondrial DNA, and
expression of cytochrome c, was observed. Vitamin A supplementation also
increased the levels of nuclear respiratory factor (NFR)-1 and mitochondrial
transcription factor-A (TFAM) in normal colon tissue and in colon tissue under
inflammatory conditions. CONCLUSION: The results indicate that tissue damage in
colitis is accompanied by the arrest of mitochondrial respiration, loss of
mitochondrial DNA, and the expression of mitochondrial proteins. Vitamin A
effectively protects colon mitochondria by upregulation of mitochondrial
transcription factors, NFR-1 and TFAM, and prevents inflammatory and necrotic
changes in colitis. Vitamin A is therefore a potential therapeutic agent in
inflammatory bowel disease.
PMID- 26429663
TI - Oxidative damage and antioxidant defense in thymus of malnourished lactating
rats.
AB - OBJECTIVE: Malnutrition has been associated with oxidative damage by altered
antioxidant protection mechanisms. Specifically, the aim of this study was to
evaluate oxidative damage (DNA and lipid) and antioxidant status (superoxide
dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT] mRNA, and
protein expression) in thymus from malnourished rat pups. METHODS: Malnutrition
was induced during the lactation period by the food competition method. Oxidative
DNA damage was determined quantifying 8-oxo-7, 8-dihydro-2'-deoxyguanosine adduct
by high-performance liquid chromatography. Lipid peroxidation was assessed by the
formation of thiobarbituric acid-reactive substances. Levels of gene and protein
expression of SOD, GPx, and CAT were evaluated by real-time polymerase chain
reaction and Western blot, respectively. Antioxidant enzyme activities were
measured spectrophotometrically. RESULTS: Oxidative DNA damage and lipid
peroxidation significantly increased in second-degree (MN-2) and third-degree
malnourished (MN-3) rats compared with well-nourished rats. Higher amounts of
oxidative damage, lower mRNA expression, and lower relative concentrations of
protein, as well as decreased antioxidant activity of SOD, GPx, and CAT were
associated with the MN-2 and MN-3 groups. CONCLUSIONS: The results of this study
demonstrated that higher body-weight deficits were related to alterations in
antioxidant protection, which contribute to increased levels of damage in the
thymus. To our knowledge, this study demonstrated for the first time that early
in life, malnutrition leads to increased DNA and lipid oxidative damage,
attributable to damaged antioxidant mechanisms including transcriptional and
enzymatic activity alterations. These findings may contribute to the elucidation
of the causes of previously reported thymus dysfunction, and might explain
partially why children and adults who have overcome child undernourishment
experience immunologic deficiencies.
PMID- 26429664
TI - Effects and mechanisms of auricular vagus nerve stimulation on high-fat-diet-
induced obese rats.
AB - OBJECTIVE: Obesity is a major public health problem. Regulating food intake and
promoting metabolism of fat are two important options for treating obesity.
Auricular vagus nerve stimulation (AVNS) is considered as an alternative approach
to vagal nerve stimulation. The aim of this study was to investigate the effects
of AVNS and its mechanisms on obesity in obese rats. METHODS: Male Sprague-Dawley
rats were fed either a high-fat diet (HFD) or a normal diet for 8 wk. Qualified
HFD rats were randomly divided into three groups: the HFD group, the AVNS group,
and the sham group for 6 wk treatment. Body weight and daily energy intake were
recorded weekly. The rats were sacrificed for measurement of weight of bilateral
perirenal, epididymal white adipose tissue (WAT), dorsal brown adipose tissue
(BAT), and gastric emptying. Serum cholecystokinin (CCK), peptide YY3 to 36 (PYY3
36) and norepinephrine (NE) were assayed by enzyme-linked immunosorbent assay.
Real-time quantitative polymerase chain reaction was used to assess the mRNA
expressions of CCK subtype receptor a (CCKa) in the antrum, PYY3-36 receptor in
the distal ileum, beta3-adrenoceptor, and uncoupling protein gene 1 (UCP1) in the
BAT. RESULTS: Compared with HFD group, AVNS significantly reduced body weight and
epididymal WAT and increased BAT weight, serum NE, mRNA expressions of beta3
adrenoceptors, and UCP1 of the BAT, but had no effect on daily energy intake,
perirenal WAT weight, gastric emptying, serum levels of CCK and PYY, or mRNA
expressions of CCKa receptor and PYY3-36 receptor in the relevant tissues. The
sham group, as a comparison group for AVNS, saw less effect in any of the indexes
compared with the HFD group. AVNS had more effect on weight loss, reduction of
perirenal WAT, and increase of NE, beta3-adrenoceptor, and UCP1 than sham.
CONCLUSIONS: AVNS was more effective in reducing body weight and causing visceral
fat loss. Biochemical tests found more NE released in the serum and more beta3
adrenoceptor and UCP1 expression in the BAT. All of these features suggested that
energy expenditure might play an important role in obesity management by AVNS.
PMID- 26429665
TI - omega-3 Fatty acids reverse lipotoxity through induction of autophagy in
nonalcoholic fatty liver disease.
AB - OBJECTIVE: The aim of this study was to evaluate the effect of omega-3 fatty
acids on nonalcoholic fatty liver disease concerning hepatocyte lipid
accumulation as well as apoptosis induced by free fatty acids (FFAs) and to
explore the underlying mechanism involving autophagy. METHODS: Hepatocytes were
incubated with a mixture of free fatty acids (FFAs) to mimic in vitro
lipotoxicity in the pathogenesis of nonalcoholic fatty liver disease, presented
by lipid accumulation and cellular apoptosis. Chemical inhibitor or inducer of
autophagy and genetic deficit cells, as well as omega-3 fatty acids were used as
intervention. The autophagic role of omega-3 fatty acids was investigated using
Western blot and immunofluorescence. The underlying mechanism of omega-3 fatty
acids involving autophagy was preliminarily explored by quantitative real-time
polymerase chain reaction and Western blot. RESULTS: FFAs induce lipid
accumulation and apoptosis in hepatocytes. Inhibition or genetic defect of
autophagy increases lipid accumulation induced by FFA, whereas induction acts
inversely. omega-3 Fatty acids reduced lipid accumulation and inhibited apoptosis
induced by FFA. omega-3 Fatty acids induced autophagy by downregulating stearoyl
CoA desaturase 1 expression in hepatocytes. CONCLUSION: omega-3 Fatty acids exert
protective effects on hepatocytes against lipotoxicity through induction of
autophagy, as demonstrated by inhibition of lipid accumulation and apoptosis.
PMID- 26429667
TI - Addition of lipids to parenteral nutrition does not cause fungal infections.
AB - Parenteral nutrition (PN) that includes lipid emulsion is considered to increase
both bacterial and fungal central venous catheter-related bloodstream infections.
This concept is based on several erroneous metrics: Reports in age-old literature
at a time when preparing PN admixtures lacked stringent quality control, when its
infusion, the techniques of insertion, maintenance of vascular access devices,
and delivery systems were not well identified or enforced. Additionally, concepts
of glucohomeostasis were different and higher glucose levels were accepted. We
provide updated information with supporting literature to show that associating
PN with lipids with an increase in bloodstream infections is not justified.
PMID- 26429666
TI - Dietary fats significantly influence the survival of penumbral neurons in a rat
model of chronic ischemic by modifying lipid mediators, inflammatory biomarkers,
NOS production, and redox-dependent apoptotic signals.
AB - OBJECTIVE: Brain stroke is the third most important cause of death in developed
countries. We studied the effect of different dietary lipids on the outcome of a
permanent ischemic stroke rat model. METHODS: Wistar rats were fed diets
containing 7% commercial oils (S, soybean; O, olive; C, coconut; G, grape seed)
for 35 d. Stroke was induced by permanent middle cerebral artery occlusion.
Coronal slices from ischemic brains and sham-operated animals were supravitally
stained. Penumbra and core volumes were calculated by image digitalization after
24, 48, and 72 h poststroke. Homogenates and mitochondrial fractions were
prepared from different zones and analyzed by redox status, inflammatory markers,
ceramide, and arachidonate content, phospholipase A2, NOS, and proteases.
RESULTS: Soybean (S) and G diets were mainly prooxidative and proinflammatory by
increasing the liberation of arachidonate and its transformation into
prostaglandins. O was protective in terms of redox homeostatic balance, minor
increases in lipid and protein damage, conservation of reduced glutathione,
protective activation of NOS in penumbra, and net ratio of anti-to
proinflammatory cytokines. Apoptosis (caspase-3, milli- and microcalpains) was
less activated by O than by any other diet. CONCLUSION: Dietary lipids modulate
NOS and PLA2 activities, ceramide production, and glutathione import into the
mitochondrial matrix, finally determining the activation of the two main protease
systems involved in programmed cell death. Olive oil appears to be a biological
source for the isolation of protective agents that block the expansion of brain
core at the expense of penumbral neurons.
PMID- 26429668
TI - A glance at ... telomeres, oxidative stress, antioxidants, and biological aging.
PMID- 26429669
TI - Institutional logic in self-management support: coexistence and diversity.
AB - The prevalence of chronic conditions in Europe has been the subject of health
political reforms that have increasingly targeted collaboration between public,
private and voluntary organisations for the purpose of supporting self-management
of long-term diseases. The international literature describes collaboration
across sectors as challenging, which implies that their respective logics are
conflicting or incompatible. In line with the European context, recent Norwegian
health policy advocates inter-sectorial partnerships. The aim of this policy is
to create networks supporting better self-management for people with chronic
conditions. The purpose of our qualitative study was to map different
understandings of self-management support in private for-profit, volunteer and
public organisations. These organisations are seen as potential self-management
support networks for individuals with chronic conditions in Norway. From December
2012 to April 2013, we conducted 50 semi-structured interviews with
representatives from relevant health and well-being organisations in different
parts of Norway. According to the theoretical framework of institutional logic,
representatives' statements are embedded with organisational understandings. In
the analysis, we systematically assessed the representatives' different
understandings of self-management support. The institutional logic we identified
revealed traits of organisational historical backgrounds, and transitions in
understanding. We found that the merging of individualism and fellowship in
contemporary health policy generates different types of logic in different
organisational contexts. The private for-profit organisations were concerned with
the logic of a healthy appearance and mindset, whereas the private non-profit
organisations emphasised fellowship and moral responsibility. Finally, the
public, illness-oriented organisations tended to highlight individual conditions
for illness management. Different types of logic may attract different users, and
simultaneously, a diversity of logic types may challenge collaboration at the
user's expense. Moral implications embed institutional logic implying a change
towards individual responsibility for disease. Policy makers ought to consider
complexities of logic in order to tailor the different needs of users.
PMID- 26429670
TI - Retinal detachment postphacoemulsification in Bichon Frises: a retrospective
study of 54 dogs.
AB - OBJECTIVE: To compare rates of retinal detachment (RD) postphacoemulsification in
American Bichon Frises with and without prophylactic retinopexy. PROCEDURES:
Medical records of 54 Bichon Frises undergoing phacoemulsification with or
without prophylactic retinopexy between 2003 and 2013 in one or both eyes were
reviewed from five Midwestern university veterinary teaching hospitals. Inclusion
criteria were preoperative ERG, at least 6 months of follow-up
postphacoemulsification, and the absence of preexisting RD as determined by
ophthalmic examination and/or ultrasound. Statistical analyses were performed
using chi-squared test, and Wilcoxon rank-sum tests and Wilson confidence
intervals with the P-value <0.05 were considered significant. RESULTS:
Phacoemulsification was performed without retinopexy in 79 eyes (42 dogs, non-PR
group) and with prophylactic retinopexy in 23 eyes (12 dogs, PR group). Incidence
of diabetes mellitus was 10/42 and 3/12 in the non-PR and the PR groups,
respectively (P = 0.93). Intraocular lens implantation was performed in 40/42 non
PR dogs and 11/12 PR dogs (P = 0.63, 73/79 vs. 21/23 eyes). At final re
examination, RD occurred in 4/79 eyes without retinopexy, compared to 0/23 RD in
the retinopexy group. There was no statistically significant difference in RD
rates between the two groups (P = 0.27). CONCLUSIONS: These data provide no
statistical evidence to support prophylactic retinopexy in Bichon Frises. Due to
the low rate of retinal detachment following phacoemulsification without
prophylactic retinopexy, the procedure appears to offer limited benefit to offset
cost, procedural risk, and risk of extended or repeated anesthesia in Bichon
Frises.
PMID- 26429671
TI - Exploring views about mindfulness groups for voice-hearing from the perspective
of service users and staff: A Q-methodology study.
AB - OBJECTIVES: Despite prevailing beliefs about the potential benefits and
harmfulness of mindfulness for people who hear voices, there is a paucity of
research into staff and service user views. Q-methodology was used to explore
views about mindfulness groups for voice-hearers. METHOD: Opportunistic sampling
of mental healthcare staff (N = 14) and service users with psychosis (N = 17).
Both samples were analysed using principle components factor analysis to identify
the range of attitudes held by staff and service users. RESULTS: Staff
participants were particularly knowledgeable and interested in mindfulness. A
single staff consensus factor was found suggesting mindfulness is helpful, and
not harmful for mental health, but uncertainty surrounded its usefulness for
voice-hearers. Service users held four distinct attitudes: (i) mindfulness helps
to calm a racing mind; (ii) mindfulness helps to manage stress; (iii) mindfulness
improves well-being, and does not alter the brain, reality beliefs, or cause
madness; and (iv) mindfulness helps with managing thoughts, fostering acceptance,
and is acceptable when delivered in a group format. CONCLUSIONS: Staff viewed
mindfulness groups for psychosis as helpful, not harmful, but were uncertain
about their utility. Consistent with previous research, service users viewed
mindfulness groups as useful to promote well-being and reduce distress for
individuals experiencing psychosis.
PMID- 26429672
TI - A novel calcium-independent cellular PLA2 acts in insect immunity and larval
growth.
AB - Phospholipase A2 (PLA2) catalyzes the position-specific hydrolysis of fatty acids
linked to the sn-2 position of phospholipids (PLs). PLA2s make up a very large
superfamily, with more than known 15 groups, classified into secretory PLA2
(sPLA2), Ca(2+)-dependent cellular PLA2 (sPLA2) and Ca(2+)-independent cellular
PLA2 (iPLA2). Only a few insect sPLA2s, expressed in venom glands and immune
tissues, have been characterized at the molecular level. This study aimed to test
our hypothesis that insects express iPLA2, using the beet armyworm, Spodoptera
exigua, our model insect. Substantial PLA2 activities under calcium-free
condition were recorded in several larval tissue preparations. The PLA2 activity
was significantly reduced in reactions conducted in the presence of a specific
iPLA2 inhibitor, bromoenol lactone (BEL). Analysis of a S. exigua hemocyte
transcriptome identified a candidate iPLA2 gene (SeiPLA2-A). The open reading
frame encoded 816 amino acid residues with a predicted molecular weight of 90.5
kDa and 6.15 pI value. Our phylogenetic analysis clustered SeiPLA2-A with the
other vertebrate iPLA2s. SeiPLA2-A was expressed in all tissues we examined,
including hemocytes, fat body, midgut, salivary glands, Malpighian tubules and
epidermis. Heterologous expression in Sf9 cells indicated that SeiPLA2-A was
localized in cytoplasm and exhibited significant PLA2 activity, which was
independent of Ca(2+) and inhibited by BEL. RNA interference (RNAi) of SeiPLA2-A
using its specific dsRNA in the fifth instar larvae significantly suppressed
iPLA2 expression and enzyme activity. dsSeiPLA2-A-treated larvae exhibited
significant loss of cellular immune response, measured as nodule formation in
response to bacterial challenge, and extended larval-to-pupal developmental time.
These results support our hypothesis, showing that SeiPLA2-A predicted from the
transcriptome analysis catalyzes hydrolysis of fatty acids from cellular PLs and
plays crucial physiological roles in insect immunity and larval growth.
PMID- 26429673
TI - Investigational drugs for the treatment of osteoarthritis.
AB - INTRODUCTION: Osteoarthritis (OA) is a common joint disease with multiple
pathophysiological processes, affecting the whole joint. Current therapeutic
options such as NSAIDs can provide a palliative effect on symptoms but have
limited effect on disease progression. New drugs targeting OA structures may
retard disease progression at an earlier stage and delay the need for joint
replacement. AREAS COVERED: Some drugs have entered into clinical trials and a
few, such as strontium ranelate, do have improvements in both pain and structure
changes. However, most of them have failed in clinical trials largely due to
increased side effects or the failure to identify the right OA phenotype for the
right drug in clinical design. This review describes various investigational
drugs developed for the treatment of OA covering those at stages from preclinical
experiments to early phase clinical trials. They include drugs for slowing
cartilage degradation, regulating cartilage metabolism, targeting subchondral
bone, controlling inflammation and relieving pain. EXPERT OPINION: Treatment
options for OA remain limited. However, with the emergence of sensitive tools to
detect early disease progression and identification of different OA phenotypes,
disease-modifying anti-OA drugs with increased benefit and reduced risks will
become available for OA treatment in the near future.
PMID- 26429674
TI - Association of antibodies to the NR1 subunit of N-methyl-D-aspartate receptors
with neuropsychiatric systemic lupus erythematosus.
AB - OBJECTIVE: To determine epitope reactivity of autoantibodies to N-methyl-D
aspartate (NMDA) receptor NR1 subunit and their association with neuropsychiatric
systemic lupus erythematosus (NPSLE). METHODS: Paired serum and CSF specimens
were obtained from 41 patients with NPSLE (22 with diffuse
psychiatric/neuropsychological syndromes [diffuse NPSLE] and 19 with neurologic
syndromes or polyneuropathy [focal NPSLE]), 21 patients with various rheumatic
diseases other than SLE (non-SLERD). Sera were also obtained from 27 SLE patients
without neuropsychiatric manifestations (non-CNS SLE). Antibodies to murine NR1
(mNR1) or to 4 different preparations of synthetic 25-amino-acid (AA) peptides of
human NR1 were measured by enzyme-linked immune sorbent assay (ELISA). RESULTS:
Serum anti-mNR1 levels were significantly higher in NPSLE than in non-SLERD. Sera
from NPSLE patients bound efficiently to the AA residues 19-44 from the N
terminus of NR1 (NR1-A) or 56-81 (NR1-C). Accordingly, serum anti-NR1-A and anti
NR1-C were also elevated in NPSLE compared with non-SLERD. Of note, anti-NR1-A as
well as anti-NR1-C levels in CSF, but not in sera, were significantly elevated in
diffuse NPSLE compared with focal NPSLE or with non-SLERD. CONCLUSION: These
results suggest that autoantibodies to NMDA receptor NR1, especially to the AA
residues 19-44 and 56-81 from the N-terminus play a pivotal role in the
pathogenesis of diffuse NPSLE.
PMID- 26429676
TI - Prophylactic HPV vaccination: past, present, and future.
AB - Human papillomavirus (HPV) is the necessary cause of cervical cancer, the fourth
most common cancer and cause of cancer-related death in females worldwide. HPV
also causes anal, vaginal, vulvar, penile, and oropharyngeal cancer. Prophylactic
HPV vaccines based on recombinantly expressed virus-like particles have been
developed. Two first-generation, U.S. Food and Drug Administration (FDA)-approved
vaccines prevent infections and disease caused by HPV16 and HPV18, the two HPV
genotypes that cause approximately 70% of cervical cancer, and one of these
vaccines also prevents HPV6 and HPV11, the two HPV genotypes that cause 90% of
genital warts. A next-generation vaccine, recently approved by the U.S. FDA,
targets HPV16, HPV18, and five additional HPV genotypes that together causes
approximately 90% of cervical cancer as well as HPV6 and HPV11. In clinical
trials, these vaccines have shown high levels of efficacy against disease and
infections caused by the targeted HPV genotypes in adolescent females and males
and older females. Data indicate population effectiveness, and therefore cost
effectiveness, is highest in HPV-naive young females prior to becoming sexually
active. Countries that implemented HPV vaccination before 2010 have already
experienced decreases in population prevalence of targeted HPV genotypes and
related anogenital diseases in women and via herd protection in heterosexual men.
Importantly, after more than 100 million doses given worldwide, HPV vaccination
has demonstrated an excellent safety profile. With demonstrated efficacy, cost
effectiveness, and safety, universal HPV vaccination of all young, adolescent
women, and with available resources at least high-risk groups of men, should be a
global health priority. Failure to do so will result in millions of women dying
from avertable cervical cancers, especially in low- and middle-income countries,
and many thousands of women and men dying from other HPV-related cancers.
PMID- 26429675
TI - [Antidepressants in the elderly].
AB - Depression in the elderly is a changing, difficult and common disorder. At this
age, there are more relapses and more long-life treatment is required. The
pharmacology approach is a challenge because of concurrent factors that make
their treatment more difficult. It is very important to have a basic
antidepressant scheme, in order to help treat this disorder with efficiency and
success from Primary Care. There are no drugs without side effects, and their
characteristics have to be known in order to make the right selection depending
on effectiveness, safety and tolerance.
PMID- 26429677
TI - Assessment of Pain Intensity in Patients with Dentin Hypersensitivity After
Application of Prophylaxis Paste Based on Calcium Sodium Phosphosilicate Formula.
AB - BACKGROUND: One of many functions of the pulp-dentin complex is sensory function.
Acute, situated, receding pain after the cessation of the stimulus action is
called dentin pain. Dentin hypersensitivity has been described as one of the most
painful and least successfully treated chronic ailments of teeth. The aim of this
research was the clinical evaluation of the effectiveness of professional
polishing paste containing calcium sodium phosphosilicate formula (NovaMin) in
eliminating dentin hypersensitivity after a single application. MATERIAL AND
METHODS: The study comprised 92 teeth with dentin hypersensitivity diagnosed on
the basis of history and clinical examination. The pain reaction of exposed
dentine was induced by tactile and dehydrating stimuli, asking patients to assess
the severity of pain on the VAS scale. Clinical trial and survey were carried out
twice: before and 1 week after the application of the polishing paste. RESULTS:
After the application of the examined paste, the percentage of teeth reacting
with a severe pain to the touch of the probe decreased from 16.3% to 4.3%, and
with a moderate pain from 42.4% to 12%. Examination after applying dehydrating
stimulus a week after carrying out the application showed a decrease in the
proportion of teeth with strong pain from 28.3% to 0% and moderate pain from 38%
to 15.2%. The lack of pain increased from 12% to about 50%. CONCLUSIONS: The use
of prophylactic professional paste with NovaMin formula in in-office procedure
provides the reduction of dentin hypersensitivity noticeable by 1 week after
application.
PMID- 26429678
TI - Psychiatric classification - a developmental perspective.
AB - Current classification systems treat developmental and adult psychopathologies as
separate. However, as risk factors for psychiatric disorders are identified it is
increasingly clear that these can lead to multiple outcomes across different
developmental stages. Research and classification schemes will therefore in the
future need to adopt a lifespan approach to risk.
PMID- 26429679
TI - Mood instability: significance, definition and measurement.
AB - Mood instability is common, and an important feature of several psychiatric
disorders. We discuss the definition and measurement of mood instability, and
review its prevalence, characteristics, neurobiological correlates and clinical
implications. We suggest that mood instability has underappreciated
transdiagnostic potential as an investigational and therapeutic target.
PMID- 26429680
TI - The famous case of Alice Cooper - psychiatry in pictures.
PMID- 26429681
TI - Psychological treatment for depression and anxiety associated with dementia and
mild cognitive impairment.
AB - Depression and anxiety are commonly associated with cognitive impairment. A
systematic review of psychological treatments that appears in this issue of the
Journal highlights the current paucity of good-quality data, but suggests these
interventions hold promise. Given the increasing burden of dementia in our
community, novel adequately powered randomised controlled trials in this area are
urgently needed.
PMID- 26429682
TI - Early intervention in psychosis: still the 'best buy'?
AB - High-quality services for people with psychosis are essential. However, in this
debate David Castle questions whether separate early intervention services are
the best option and argues instead for an integrated approach. Swaran Singh
responds, robustly defending the value of early intervention services.
PMID- 26429686
TI - Association between poor oral health and eating disorders: systematic review and
meta-analysis.
AB - BACKGROUND: There is a well-established link between oral pathology and eating
disorders in the presence of self-induced vomiting. There is less information
concerning this relationship in the absence of self-induced vomiting, in spite of
risk factors such as psychotropic-induced dry mouth, nutritional deficiency or
acidic diet. AIMS: To determine the association between eating disorder and poor
oral health, including any difference between patients with and without self
induced vomiting. METHOD: A systematic search was made of Medline, PsycINFO,
EMBASE and article bibliographies. Outcomes were dental erosion, salivary gland
function and the mean number of decayed, missing and filled teeth or surfaces
(DMFT/S). RESULTS: Ten studies had sufficient data for a random effects meta
analysis (psychiatric patients n = 556, controls n = 556). Patients with an
eating disorder had five times the odds of dental erosion compared with controls
(95% CI 3.31-7.58); odds were highest in those with self-induced vomiting (odds
ratio (OR) = 7.32). Patients also had significantly higher DMFS scores (mean
difference 3.07, 95% CI 0.66-5.48) and reduced salivary flow (OR = 2.24, 95% CI
1.44-3.51). CONCLUSIONS: These findings highlight the importance of collaboration
between dental and medical practitioners. Dentists may be the first clinicians to
suspect an eating disorder given patients' reluctance to present for psychiatric
treatment, whereas mental health clinicians should be aware of the oral
consequences of inappropriate diet, psychotropic medication and self-induced
vomiting.
PMID- 26429684
TI - Psychological treatments for depression and anxiety in dementia and mild
cognitive impairment: systematic review and meta-analysis.
AB - BACKGROUND: Anxiety and depression are common in people with dementia and mild
cognitive impairment (MCI), but there is uncertainty about the effectiveness of
both pharmacological and psychological therapies. AIMS: To evaluate the evidence
of effectiveness of psychological treatments in treating depression and anxiety
in people with dementia and MCI. METHOD: We carried out a systematic review and
meta-analysis of randomised controlled trials (RCTs) of psychological treatment
versus usual care in people with dementia and MCI. Primary outcomes were symptoms
of anxiety and depression. Secondary outcomes were quality of life, ability to
perform daily activities, neuropsychiatric symptoms, cognition and caregivers'
self-rated depressive symptoms. RESULTS: We included six RCTs, involving 439
participants with dementia, which used cognitive-behavioural therapy,
interpersonal therapy, counselling or multimodal interventions including a
specific psychological therapy. We found beneficial effects for both depression
and anxiety. Overall, the quality of the evidence was moderate for depression and
low for anxiety, due to the methodological limitations of the studies we
identified and the limited number of trials. CONCLUSIONS: The evidence from six
RCTs suggests that psychological treatments are effective in reducing symptoms of
depression and anxiety for people with dementia. There is a need for high
quality, multicentre trials including standardised, well-defined interventions.
PMID- 26429687
TI - Could Marcus Aurelius be the missing link in the insanity defence? - psychiatry
in history.
PMID- 26429688
TI - Ethnic differences in BDNF Val66Met polymorphism.
PMID- 26429689
TI - Authors' reply.
PMID- 26429690
TI - Relevance of 123I-FP-CIT SPECT brain scans in routine clinical settings.
PMID- 26429692
TI - Correction.
PMID- 26429691
TI - Authors' reply.
PMID- 26429693
TI - Kaleidoscope.
PMID- 26429696
TI - [The femoral vein alternate path as for cardiac pacing final: Experience center].
PMID- 26429697
TI - The role of high flow oxygen therapy in acute respiratory failure.
AB - Acute respiratory failure represents one of the most common causes of intensive
care unit admission and oxygen therapy remains the first-line therapy in the
management of these patients. In recent years, high-flow oxygen via nasal cannula
has been described as a useful alternative to conventional oxygen therapy in
patients with acute respiratory failure. High-flow oxygen via nasal cannula
rapidly alleviates symptoms of acute respiratory failure and improves oxygenation
by several mechanisms, including dead space washout, reduction in oxygen dilution
and inspiratory nasopharyngeal resistance, a moderate positive airway pressure
effect that may generate alveolar recruitment and an overall greater tolerance
and comfort with the interface and the heated and humidified inspired gases.
However, the experience in adults is still limited and there are no clinical
guidelines to establish recommendations for their use. This article aims to
review the existing evidence on the use of high-flow oxygen via nasal cannula in
adults with acute respiratory failure and its possible applications, advantages
and limitations.
PMID- 26429698
TI - Fc Receptor-mediated Effector Function Contributes to the Therapeutic Response of
Anti-TNF Monoclonal Antibodies in a Mouse Model of Inflammatory Bowel Disease.
AB - BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] monoclonal antibodies
[infliximab, adalimumab] induce complete mucosal healing in a proportion of
patients with Crohn's disease whereas a TNF receptor fusion protein [etanercept]
is not effective and the anti-TNF F[ab']2 fragment [certolizumab] shows a very
low rate of complete mucosal healing. In contrast, all four TNF-neutralising
drugs have demonstrated efficacy in the treatment of rheumatoid arthritis. These
observations suggest that factors other than neutralisation of TNF may contribute
to clinical outcomes in Crohn's disease. Here we tested the hypothesis that Fc
receptor [FcR]-mediated effects may contribute to the therapeutic response of
anti-TNF antibodies in inflammatory bowel disease. METHODS: We modified an IgG2c
mouse anti-TNF antibody that binds the high-affinity FcRs to generate an IgG1
isotype with strongly diminished binding. We examined the therapeutic effects of
both antibodies in the T cell transfer model of inflammatory bowel disease and
the collagen-induced arthritis model. RESULTS: The IgG2c anti-TNF antibody
prevented colonic inflammation in the T cell transfer model of colitis, whereas
the IgG1 anti-TNF did not. Conversely, both the IgG2c and IgG1 anti-TNFs were
similarly effective in reducing the severity of articular inflammation in mouse
collagen-induced arthritis. CONCLUSION: These data support the concept that the
mechanism of action for TNF-neutralising drugs may differ across immune-mediated
diseases and, potentially, between therapeutics within a particular disease. Our
data suggest a specific role of Fc-mediated immune regulation in the resolution
of intestinal inflammation by anti-TNF monoclonal antibodies.
PMID- 26429699
TI - Shotgun assembly of the mitochondrial genome from Fenneropenaeus penicillatus
with phylogenetic consideration.
AB - The complete mitochondrial genome is of great importance for better understanding
of the genome-level characteristics and phylogenetic relationships among related
species. In this study, Fenneropenaeus penicillatus mitochondrial genome sequence
was determined by next-generation sequencing. The complete genome DNA was 16,040
bp in length and consisted of a typical set of 13 protein-coding genes, 22
transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes and a putative control
region (CR). The gene arrangement is identical to the pancrustacean pattern. The
overall base composition of its mitochondrial genome is estimated to be 34.1% for
A, 34.1% for T, 12.5% for G and 19.3% for C with a high A+T content (68.2%). The
analysis of the average Ka/Ks in the 13 mitochondrial protein-coding genes of
penaeid shrimps indicated a strong purifying selection within this group. The
phylogenetic analysis based on mitochondrial sequences and 13 concatenated
protein-coding genes showed strong statistic support for the following
relationship among the five genera ((Penaeus
s.s+Fenneropenaeus)+(Litopenaeus+Farfantepenaeus))+Marsupenaeus. The sequence
data of F. penicillatus can provide useful information for the studies on
molecular systematics, population structure, stock evaluation and conservation
genetics.
PMID- 26429701
TI - Prevention of malaria in pregnancy: a fork in the road?
PMID- 26429700
TI - Intermittent screening and treatment or intermittent preventive treatment with
dihydroartemisinin-piperaquine versus intermittent preventive treatment with
sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western
Kenya: an open-label, three-group, randomised controlled superiority trial.
AB - BACKGROUND: Every year, more than 32 million pregnancies in sub-Saharan Africa
are at risk of malaria infection and its adverse consequences. The effectiveness
of the intermittent preventive treatment with sulfadoxine-pyrimethamine strategy
recommended by WHO is threatened by high levels of parasite resistance. We aimed
to assess the efficacy and safety of two alternative strategies: intermittent
screening with malaria rapid diagnostic tests and treatment of women who test
positive with dihydroartemisinin-piperaquine, and intermittent preventive
treatment with dihydroartemisinin-piperaquine. METHODS: We did this open-label,
three-group, randomised controlled superiority trial at four sites in western
Kenya with high malaria transmission and sulfadoxine-pyrimethamine resistance.
HIV-negative pregnant women between 16 and 32 weeks' gestation were randomly
assigned (1:1:1), via computer-generated permuted-block randomisation (block
sizes of three, six, and nine), to receive intermittent screening and treatment
with dihydroartemisinin-piperaquine, intermittent preventive treatment with
dihydroartemisinin-piperaquine, or intermittent preventive treatment with
sulfadoxine-pyrimethamine. Study participants, study clinic nurses, and the study
coordinator were aware of treatment allocation, but allocation was concealed from
study investigators, delivery unit nurses, and laboratory staff. The primary
outcome was malaria infection at delivery, defined as a composite of peripheral
or placental parasitaemia detected by placental histology, microscopy, or rapid
diagnostic test. The primary analysis was by modified intention to treat. This
study is registered with ClinicalTrials.gov, number NCT01669941. FINDINGS:
Between Aug 21, 2012, and June 19, 2014, we randomly assigned 1546 women to
receive intermittent screening and treatment with dihydroartemisinin-piperaquine
(n=515), intermittent preventive treatment with dihydroartemisinin-piperaquine
(n=516), or intermittent preventive treatment with sulfadoxine-pyrimethamine
(n=515); 1368 (88%) women comprised the intention-to-treat population for the
primary endpoint. Prevalence of malaria infection at delivery was lower in the
intermittent preventive treatment with dihydroartemisinin-piperaquine group than
in the intermittent preventive treatment with sulfadoxine-pyrimethamine group (15
[3%] of 457 women vs 47 [10%] of 459 women; relative risk 0.32, 95% CI 0.18-0.56;
p<0.0001), but not in the intermittent screening and treatment with
dihydroartemisinin-piperaquine group (57 [13%] of 452 women; 1.23, 0.86-1.77;
p=0.26). Compared with intermittent preventive treatment with sulfadoxine
pyrimethamine, intermittent preventive treatment with dihydroartemisinin
piperaquine was associated with a lower incidence of malaria infection during
pregnancy (192.0 vs 54.4 events per 100 person-years; incidence rate ratio [IRR]
0.28, 95% CI 0.22-0.36; p<0.0001) and clinical malaria during pregnancy (37.9 vs
6.1 events; 0.16, 0.08-0.33; p<0.0001), whereas intermittent screening and
treatment with dihydroartemisinin-piperaquine was associated with a higher
incidence of malaria infection (232.0 events; 1.21, 1.03-1.41; p=0.0177) and
clinical malaria (53.4 events; 1.41, 1.00-1.98; p=0.0475). We recorded 303
maternal and infant serious adverse events, which were least frequent in the
intermittent preventive treatment with dihydroartemisinin-piperaquine group.
INTERPRETATION: At current levels of rapid diagnostic test sensitivity,
intermittent screening and treatment is not a suitable alternative to
intermittent preventive treatment with sulfadoxine-pyrimethamine in the context
of high sulfadoxine-pyrimethamine resistance and malaria transmission. However,
dihydroartemisinin-piperaquine is a promising alternative drug to replace
sulfadoxine-pyrimethamine for intermittent preventive treatment. Future studies
should investigate the efficacy, safety, operational feasibility, and cost
effectiveness of intermittent preventive treatment with dihydroartemisinin
piperaquine. FUNDING: The Malaria in Pregnancy Consortium, which is funded
through a grant from the Bill & Melinda Gates Foundation to the Liverpool School
of Tropical Medicine.
PMID- 26429702
TI - Rescue microsurgery with bypass and stent removal following Pipeline treatment of
a giant internal carotid artery terminus aneurysm.
AB - We report the microsurgical rescue and removal of a Pipeline stent embolization
of a giant internal carotid artery terminus aneurysm. After the initial placement
of a Pipeline Embolization Device (PED), it migrated proximally to the cavernous
carotid with the distal end free in the middle of the aneurysm, resulting in only
partial aneurysm neck coverage. The patient underwent microsurgical rescue with
trapping, bypass, and opening of the aneurysm with PED removal. The vessel
remained patent in the proximal segment previously covered by the Pipeline stent.
Microsurgical rescue for definitive aneurysm treatment with PED removal can be
safe and effective for aneurysms unsuccessfully treated with PED.
PMID- 26429703
TI - Reply letter to the editor: the continuing story of George Gershwin and his brain
tumor--would the outcome have been different today?
PMID- 26429704
TI - Economic burden and catastrophic cost among people living with type2 diabetes
mellitus attending a tertiary health institution in south-east zone, Nigeria.
AB - BACKGROUND: Diabetes mellitus (DM) is a life-long illness that affects the
quality of life, requiring close monitoring and control. Type 2 DM is preventable
and controllable but increasing cost of care could hinder access to quality care
because of inability to pay leading to high morbidity, mortality and productivity
losses. The people living with diabetes mellitus (PLWD) in Nigeria have high risk
for high economic burden and catastrophic expenditure not only because they make
frequent visits to the health facilities, report late with complications but also
pay out of pocket at the point of accessing care. The aim of this study was to
assess the magnitude of economic burden borne and catastrophic costs incurred by
PLWD in Nigeria. METHODS: Cross-sectional descriptive survey design was used to
study a sample of 308 type2 PLWD managed at a tertiary health institution, South
east Nigeria using semi-structured, prevalidated questionnaire. Data collection
period was 2 months. RESULTS: The major findings were economic burden of type 2
DM of N56,245 ($356). Catastrophic direct cost was 45 % at 30 % threshold (the
determinant level for catastrophic spending set). All socio-economic status (SES)
groups suffered catastrophic expenditure but the poorest quartile had the highest
incidence. CONCLUSIONS: Economic burden of DM was high for PLWD who also suffered
high catastrophic costs due to the impact of out of pocket payment. PLWD need
financial protection especially for the poorest since they buy from the same
market and incur same costs. Policy decision making to assist the PLWD cope with
cost of care is needful in Nigeria and nations with related problems.
PMID- 26429705
TI - Social determinants of duration of last nursing home stay at the end of life in
Switzerland: a retrospective cohort study.
AB - BACKGROUND: Due to demographic ageing and increasing life expectancy, a growing
demand for long-term nursing home care can be expected. Stays in nursing homes
appear to be more socially determined than hospital stays. We therefore looked at
the impact of socio-demographic and health care variables on the length of the
last nursing home stay. METHODS: Nationwide individual data from nursing homes
and hospitals in Switzerland were linked with census and mortality records.
Gender-specific negative binomial regression models were used to analyze N =
35,739 individuals with an admission age of at least 65 years and deceased in
2007 or 2008 in a nursing home. RESULTS: Preceding death, men spent on average
790 days and women 1250 days in the respective nursing home. Adjusted for
preceding hospitalizations, care level, cause of death and multimorbidity, a low
educational level, living alone or being tenant as well as a low care level at
the admission time increased the risk for longer terminal stays. Conversely, a
high educational level, being homeowner, being married as well as a high care
level at the admission time decreased the risk for longer stays. DISCUSSION: The
length of the last nursing home stay before death was not only dependent on
health-related factors alone, but also substantially depended on socio
demographic determinants such as educational level, homeownership or marital
status. The support of elderly people at the admission time of a presumably
following nursing home stay should be improved and better evaluated in order to
reduce unnecessary and undesired long terminal nursing home stays. CONCLUSIONS:
Health policy should aim at diminishing the role of situational, non-health
related factors in order to empower people to spend the last years before death
according to individual needs and preferences.
PMID- 26429706
TI - Idiopathic Inflammatory Myopathies and Malignancy: a Comprehensive Review.
AB - The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of
autoimmune diseases (collectively known as myositis) affecting the skeletal
muscles as well as other organ systems such as skin, lungs, and joints. The
primary forms of myositis include polymyositis (PM), dermatomyositis (PM), and
immune-mediated necrotizing myopathy (IMNM). Patients with these diseases
experience progressive proximal muscle weakness, have characteristic muscle
biopsy findings, and produce autoantibodies that are associated with unique
clinical features. One distinguishing feature of these patients is that they are
also known to have an increased risk of cancer. Since the first description of
the association in 1916, it has been extensively reported in the medical
literature. However, there have been significant variations between the different
studies with regard to the degree of cancer risk in patients with IIM. These
discrepancies can, in part, be attributed to differences in the definition of
malignancy-associated myositis used in different studies. In recent years,
significant advances have been made in defining specific features of IIM that are
associated with the development of malignancy. One of these has been myositis
specific antibodies (MSAs), which are linked to distinct clinical phenotypes and
categorize patients into groups with more homogeneous features. Indeed, patients
with certain MSAs seem to be at particularly increased risk of malignancy. This
review attempts a systematic evaluation of research regarding the association
between malignancy and myositis.
PMID- 26429707
TI - Idiopathic Inflammatory Myopathies: an Update on Classification and Treatment
with Special Focus on Juvenile Forms.
AB - Juvenile inflammatory myopathies represent a heterogeneous group of rare and
potentially fatal disorders of unknown aetiology, characterised by inflammation
and proximal and symmetric muscle weakness. Beyond many similarities, specific
clinical, laboratoristic and histopathologic features underlie different subsets
with distinguishing demographic, prognostic and therapeutic peculiarities. Over
time, several forms of inflammatory idiopathic myopathies have been described,
including macrophagic myofascitis, immune-mediated necrozing myopathy and the
spectrum of amyopathic dermatomyositis that include hypomyopathic
dermatomyositis, inclusion body myositis and cancer-associated myositis occurring
almost exclusively in adults. However, juvenile dermatomyositis is the most
frequent in childhood, whereas polymyositis is relatively more frequent in
adults. The aetiology is nowadays widely unclear; however, current theories
contemplate a combination of environmental triggers, immune dysfunction and
specific tissue responses involving muscle, skin and small vessels endothelium in
genetically susceptible individuals. Myositis-specific autoantibodies, found
almost exclusively in patients with myositis and myositis-associated
autoantibodies, detectable both among patients with myositis and in subjects
suffering from other autoimmune diseases, have an important clinical role because
of their relation to specific clinical features, response to therapy and
prognosis. The gold standard treatment for juvenile dermatomyositis is
represented by corticosteroids, along with adjunctive steroid-sparing
immunosuppressive therapies, which are used to counteract disease activity,
prevent mortality, and reduce long-term disability. Further treatment approach
such as biologic agents and autologous stem cell transplantation are emerging
during the last years, in particular in patients difficult to treat and with poor
prognosis. Therefore, a highly medical specialised approach is required for
diagnosis and management of these conditions. This review comprehensively
examines juvenile inflammatory myopathies focusing on clinical and laboratory
classifications as well as on the current treatment approaches, referring in
particular on biologic agents and latest therapeutic opportunities.
PMID- 26429708
TI - TumorTracer: a method to identify the tissue of origin from the somatic mutations
of a tumor specimen.
AB - BACKGROUND: A substantial proportion of cancer cases present with a metastatic
tumor and require further testing to determine the primary site; many of these
are never fully diagnosed and remain cancer of unknown primary origin (CUP). It
has been previously demonstrated that the somatic point mutations detected in a
tumor can be used to identify its site of origin with limited accuracy. We
hypothesized that higher accuracy could be achieved by a classification algorithm
based on the following feature sets: 1) the number of nonsynonymous point
mutations in a set of 232 specific cancer-associated genes, 2) frequencies of the
96 classes of single-nucleotide substitution determined by the flanking bases,
and 3) copy number profiles, if available. METHODS: We used publicly available
somatic mutation data from the COSMIC database to train random forest classifiers
to distinguish among those tissues of origin for which sufficient data was
available. We selected feature sets using cross-validation and then derived two
final classifiers (with or without copy number profiles) using 80 % of the
available tumors. We evaluated the accuracy using the remaining 20 %. For further
validation, we assessed accuracy of the without-copy-number classifier on three
independent data sets: 1669 newly available public tumors of various types, a
cohort of 91 breast metastases, and a set of 24 specimens from 9 lung cancer
patients subjected to multiregion sequencing. RESULTS: The cross-validation
accuracy was highest when all three types of information were used. On the left
out COSMIC data not used for training, we achieved a classification accuracy of
85 % across 6 primary sites (with copy numbers), and 69 % across 10 primary sites
(without copy numbers). Importantly, a derived confidence score could distinguish
tumors that could be identified with 95 % accuracy (32 %/75 % of tumors
with/without copy numbers) from those that were less certain. Accuracy in the
independent data sets was 46 %, 53 % and 89 % respectively, similar to the
accuracy expected from the training data. CONCLUSIONS: Identification of primary
site from point mutation and/or copy number data may be accurate enough to aid
clinical diagnosis of cancers of unknown primary origin.
PMID- 26429710
TI - From 2D to 3D--a New Dimension for Modelling the Effect of Natural Products on
Human Tissue.
AB - Natural products, or their synthetic derivatives are a treasure trove to find
potential candidates for novel drugs for human treatment. The selection of
diamonds from the huge pile of worthless stone is a critical--and difficult-
stage in the discovery pipeline. Of all the factors to be considered, perhaps the
most important, is that the compound should have the desired effect on the tissue
in vivo. Since it is not possible (or ethical) to test all compounds in vivo one
must preselect using a surrogate assay system. While animal models have the
advantage of being holistic and current 3D culture systems are reductionistic,
they at least can be constructed from human cell types. In this review we will
consider some of the evidence demonstrating that cells grown in 3D cultures have
physiological performances that mimic functions seen in human tissues
significantly better than cells grown using classical 2D culture systems. We will
discuss advantages and disadvantages of these new culture technologies and
highlight theoretical reasons for the differences. 3D cell culture technologies
are more labour intensive than 2D culture systems and therefore their
introduction is a trade-off between the value of obtaining data that is more
relevant to the human condition against their through-put. It is already clear
that future in vitro 3D systems will become more complex, using multiple cell
types to more faithfully represent a particular tissue or even organ system. And
one thing is sure - the diamonds are not easy to find!
PMID- 26429709
TI - Safety, efficacy, and pharmacokinetics of navitoclax (ABT-263) in combination
with irinotecan: results of an open-label, phase 1 study.
AB - PURPOSE: The oral Bcl-2 inhibitor navitoclax demonstrated activity in solid and
hematologic malignancies as monotherapy and in combination with other cytotoxic
agents in preclinical and early clinical studies. We evaluated the safety,
pharmacokinetics (PK), and antitumor activity of navitoclax plus irinotecan.
METHODS: In this multicenter, open-label, phase 1 dose escalation study, adults
with advanced solid tumors received navitoclax (starting dose 150 mg/day) in
combination with 1 of 2 irinotecan schedules during a 21-day cycle: a once-every
3-week regimen (Q3W 180, 250, or 350 mg/m(2)) or a once-weekly regimen (QW 75 or
100 mg/m(2)). Enrollment occurred until a maximum tolerated dose (MTD) and/or
recommended phase 2 dose (RPTD) was reached. RESULTS: All patients (Q3W, n = 14;
QW, n = 17) were evaluable for safety, PK, and efficacy. The most common adverse
event in both groups was diarrhea (Q3W 92.9 %; QW 76.5 %), which was the most
frequent grade 3/grade 4 adverse event (Q3W 42.9 %; QW 29.4 %). The study was
amended to exclude 4 UGT1A1*28 7/7 homozygous patients due to frequent irinotecan
related grade 3/grade 4 diarrhea and/or febrile neutropenia. No apparent PK
interactions between navitoclax and irinotecan were observed. The MTD of the
combination was exceeded in the Q3W group at the lowest dose administered. In the
QW group, the MTD and RPTD for navitoclax were 150 mg when combined with
irinotecan 75 mg/m(2). One patient in each group achieved a partial response.
CONCLUSION: The RPTD of navitoclax in combination with irinotecan 75 mg/m(2) QW
during a 21-day cycle was 150 mg in these heavily pretreated patients.
PMID- 26429711
TI - New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in
Cancer.
AB - Resistance to chemotherapeutic drugs is one of the main obstacles to effective
cancer treatment. Multidrug resistance (MDR) is defined as resistance to
structurally and/or functionally unrelated drugs, and has been extensively
investigated for the last three decades. There are two types of MDR: intrinsic
and acquired. Tumor microenvironment selection pressure leads to the development
of intrinsic MDR, while acquired resistance is a consequence of the administered
chemotherapy. A central issue in chemotherapy failure is the existence of
heterogeneous populations of cancer cells within one patient and patient-to
patient variability within each type of cancer. Numerous genes and pathways
contribute to the development of MDR in cancer. Point mutations, gene
amplification or other genetic or epigenetic changes all affect biological
functions and may lead to the occurrence of MDR phenotype. Similar to the
characteristics of cancerogenesis, the main features of MDR include abnormal
tumor vasculature, regions of hypoxia, aerobic glycolysis, and a lower
susceptibility to apoptosis. In order to achieve a lethal effect on cancer cells,
drugs need to reach their intracellular target molecules. The overexpression of
the efflux transporter P-glycoprotein (P-gp) in MDR cancer cells leads to
decreased uptake of the drug and intracellular drug accumulation, minimising drug
target interactions. New agents being or inspired by natural products that
successfully target these mechanisms are the main subject of this review. Two key
approaches in combating MDR in cancer are discussed (i) finding agents that
preserve cytotoxicity toward MDR cancer cells; (ii) developing compounds that
restore the cytotoxic activity of classic anticancer drugs.
PMID- 26429713
TI - Natural Products and Cancer Stem Cells.
AB - The development of modern technologies casts a new light on the natural products
as an invaluable source of lead compounds that could guide drug discovery. Cancer
stem cells are a subpopulation of cancer cells with a high clonogenic capacity
and the ability to reform the parental tumours upon transplantation. They have
been proposed to drive tumorigenesis and metastases. In this review, we present
the ability of forty-nine different natural products to influence the biology of
cancer stem cells.
PMID- 26429712
TI - Natural Products as Promising Therapeutics for Treatment of Influenza Disease.
AB - The influenza virus represents a permanent global health threat because it
circulates not only within but also between numerous host populations, thereby
frequently causing unexpected outbreaks in animals and humans with a generally
unpredictable course of disease and epidemiology. Conventional influenza therapy
is directed against the viral neuraminidase protein, which promotes virus release
from infected cells, and the viral ion channel M2, which facilitates viral
uncoating. However, these drugs, albeit effective, have a major drawback: their
targets are of a highly variable sequence. As a consequence, the virus can
readily acquire resistance by mutating the drug targets. Indeed, most seasonal
A/H1N1 viruses and the 2009 H1N1 virus are resistant to M2 inhibitors, and a
significant proportion of the seasonal A/H1N1 viruses are resistant to the
neuraminidase inhibitor oseltamivir. Development of new effective drugs for
treatment of disease during the regular influenza seasons and the possible
influenza pandemic represents an important goal. The results presented here point
out natural products as a promising source of low toxic and widely accessible
drug candidates for treatment of the influenza disease. Natural products combined
with new therapeutic targets and drug repurposing techniques, which accelerate
development of new drugs, serve as an important platform for development of new
influenza therapeutics.
PMID- 26429714
TI - Indolo[2,3-a]quinolizidines and Derivatives: Bioactivity and Asymmetric
Synthesis.
AB - Corynantheine alkaloids with a tetracyclic indole[2,3-a]-quinolizidine motif are
an important issue in academia and in the life science industries due to their
broad bioactivity profile. In particular, the main biological effects described
for indoloquinolizidines include analgesic, anti-inflammatory, antihypertensive,
and antiarrhythmic activities, as well as inhibition of multiple ion channels,
affinity for opioid receptors, and activity against Leishmania. For that reason,
in the last decades, numerous efforts have been invested in the development of
novel synthetic strategies to obtain the indole[2,3-a]-quinolizidine system. This
review focuses on the synthetic methodologies developed to target the most
important alkaloids of this family, and highlights the potential use of these
alkaloids or analogs to treat several diseases, ranging from cancer to
neurodegenerative disorders.
PMID- 26429715
TI - Thapsigargin, Origin, Chemistry, Structure-Activity Relationships and Prodrug
Development.
AB - Thapsigargin was originally isolated from the roots of the Mediterranean
umbelliferous plant Thapsia garganica in order to characterize the skin irritant
principle. Characteristic chemical properties and semi-syntheses are reviewed.
The biological activity was related to the subnanomolar affinity for the
sarco/endoplasmic reticulum calcium ATPase. Prolonged inhibition of the pump
afforded collapse of the calcium homeostasis and eventually apoptosis. Structure
activity relationships enabled design of an equipotent analogue containing a
linker. Conjugation of the analogue containing the linker with peptides, which
only are substrates for either prostate specific antigen (PSA) or prostate
specific membrane antigen (PSMA) enabled design of prodrugs targeting a number of
cancer diseases including prostate cancer (G115) and hepatocellular carcinoma
(G202). Prodrug G202 has under the name of mipsagargin in phase II clinical
trials shown promising properties against hepatocellular carcinoma.
PMID- 26429716
TI - "Non-Taxifolin" Derived Flavonolignans: Phytochemistry and Biology.
AB - Flavonolignans are plant natural products, composed of a flavonoid moiety and a
lignan (phenylpropanoid) part. Current literature focuses on flavonolignans
formed from taxifolin and coniferyl alcohol as e.g. silybin and its congeners
from fruit extract from the purple variety of the milk thistle (Silybum marianum)
denoted as "silymarin". This review describes chemistry and biological activity
of so far neglected "non-taxifolin" based flavonolignans, derived from apigenin,
luteolin, tricin, chrysoeriol, naringenin and eriodictyol, as the flavonoid part.
Up-to-date knowledge on hydnocarpin, hydnocarpin-D, pseudotsuganol, hydnowightin,
neohydnocarpin, palstatin, salcolins A and B, anastatins A and B, sinaiticin,
silyamandin and silandrin is summarized in the present paper. Most of non
taxifolin derived flavonolignans have been shown to exhibit in vitro and/or in
vivo anti-hepatotoxic, anti-oxidant, free radical scavenging, anti-inflammatory,
anti-proliferative, anti-cancer, chemotherapy potentiating, anti-melanogenic,
anti-bacterial, vasorelaxing, anti-platelet aggregation and/or
hypotriglyceridemic activity, often stronger than silybin. Many of these
compounds inhibited Staphylococcus aureus multidrug resistance pump NorA and
sensitized multidrug resistant cancer cell lines showing a potential as
adjuvants. Non-taxifolin derived flavonolignans are a relatively unexplored group
of compounds with interesting biological activity and great application
potential. Their detailed study could provide a new insight into the biomimetic
synthesis in order to obtain new compounds with greater activity and identify new
lead structures for the biomedicinal research.
PMID- 26429717
TI - Xenicane Natural Products: Biological Activity and Total Synthesis.
AB - The xenicanes are a large class of mostly bicyclic marine diterpenoids featuring
a cyclononane ring as a common structural denominator. After a brief introduction
into the characteristic structural features of xenicanes and some biogenetic
considerations, the major focus of this review will be on the various biological
activities that have been reported for xenicanes and on efforts towards the total
synthesis of these structures. Several xenicanes have been shown to be potent
antiproliferative agents in vitro, but activities have also been reported in
relation to inflammatory processes. However, so far, data on the possible in vivo
activity of xenicanes are lacking. The major challenge in the total synthesis of
xenicanes is the construction of the nine-membered ring. Different strategies
have been pursued to establish this crucial substructure, including Grob
fragmentation, ring-closing olefin metathesis, or Suzuki cross coupling as the
enabling transformations.
PMID- 26429718
TI - Synthesis and Pharmacological Effects of the Anti-Cancer Agent 2
Methoxyestradiol.
AB - The endogenous steroid 2-methoxyestradiol (2-ME) is a metabolite of 17beta
estradiol and its biosynthesis is well established. Moreover, 2-ME is also
biosynthesized from estrone. For several years, 2-ME was perceived as an inactive
metabolite devoid of any interesting biological activities. Since the late 1980s,
a number of biological and pharmacological studies have revealed that 2-ME
possesses interesting anti-cancer effects without any undesirable estrogen
activity. In particular, the anti-vascular effects and anti-angiogenic activities
that 2-ME exhibit, are of great interest and importance, in view of the
development of new anti-cancer drugs based on 2-ME. Several clinical trial
development programs have been initiated using the steroid 2-ME. In addition,
based on the many pharmacological activities reported for 2-ME, but also due to
the general interest in total and semi-synthesis of endogenous steroids, several
research groups working with organic synthesis have prepared this steroid.
Herein, the anti-cancer effects, the results from the clinical trial development
programs and the synthetic studies towards 2-ME, are reviewed.
PMID- 26429719
TI - Pentoxifylline-Induced Thrombocytopenia: A Case Report.
AB - Pentoxifylline-induced thrombocytopenia is rare, and information is lacking about
its presentation. We describe a 72-year-old Chinese male who developed
thrombocytopenia after initiation of pentoxifylline for the treatment of chronic
lower limb ischemia due to peripheral artery disease. Venous thromboembolism had
been ruled out with an ultrasound. Vascular surgeons had also determined there
was no indication for surgical intervention. Four days after initiation of
pentoxifylline, he developed thrombocytopenia, and his platelets were 68 *
10(3)/MUL. He was not in overt disseminated intravascular coagulation (DIC),
based on his International Society for Thrombosis and Hemostasis (ISTH) DIC score
of 4. Dengue fever, which is endemic in Singapore, was ruled out.
Pseudothrombocytopenia was also excluded with a peripheral blood film. When his
platelets continued to fall, pentoxifylline was discontinued on the fifth day of
treatment, and platelets normalized 48 hours after discontinuation.
Pentoxifylline was a probable cause of thrombocytopenia using the Naranjo Adverse
Drug Reaction Probability Scale (score = 7). The patient did not receive further
doses of pentoxifylline. Prescribers should be aware of the risk of
thrombocytopenia with pentoxifylline therapy and discontinue its use promptly if
it is suspected.
PMID- 26429720
TI - Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion
in Patients with High-Grade, High-Volume Disseminated Mucinous Appendiceal
Neoplasms.
AB - BACKGROUND: High-grade (HG) mucinous appendiceal neoplasms (MAN) have a worse
prognosis than low-grade histology. Our objective was to assess the safety and
efficacy of cytoreductive surgery with hyperthermic intraperitoneal
chemoperfusion (CRS/HIPEC) in patients with high-grade, high-volume (HG-HV)
peritoneal metastases in whom the utility of this aggressive approach is
controversial. METHODS: Prospectively collected perioperative data were compared
between patients with peritoneal metastases from HG-HV MAN, defined as simplified
peritoneal cancer index (SPCI) >=12, and those with high-grade, low-volume (HG
LV; SPCI <12) disease. Kaplan-Meier curves and multivariate Cox regression models
identified prognostic factors affecting oncologic outcomes. RESULTS: Overall, 54
patients with HG-HV and 43 with HG-LV peritoneal metastases underwent CRS/HIPEC.
The HG-HV group had longer operative time, increased blood loss/transfusion, and
increased intensive care unit length of stay (p < 0.05). Incomplete macroscopic
cytoreduction (CC-1/2/3) was higher in the HG-HV group compared with the HG-LV
group (68.5 vs. 32.6 %; p = 0.005). Patients with HG-HV disease demonstrated
worse survival than those with HG-LV disease (overall survival [OS] 17 vs. 42 m,
p = 0.009; time to progression (TTP) 10 vs. 14 m, p = 0.024). However, when
complete macroscopic resection (CC-0) was achieved, the OS and progression-free
survival of patients with HG-HV disease were comparable with HG-LV disease (OS 56
vs. 52 m, p = 0.728; TTP 20 vs. 19 m, p = 0.393). In a multivariate Cox
proportional hazard regression model, CC-0 resection was the only significant
predictor of improved survival for patients with HG-HV disease. CONCLUSIONS:
Although patients with HG-HV peritoneal metastases from MAN have worse prognosis
compared with patients with HG-LV disease, their survival is comparable when
complete macroscopic cytoreduction is achieved.
PMID- 26429721
TI - Brevibacterium metallicus sp. nov., an endophytic bacterium isolated from roots
of Prosopis laegivata grown at the edge of a mine tailing in Mexico.
AB - A Gram-positive, aerobic, nonmotile strain, NM2E3(T) was identified as
Brevibacterium based on the 16S rRNA gene sequence analysis and had the highest
similarities to Brevibacterium jeotgali SJ5-8(T) (97.3 %). This novel bacterium
was isolated from root tissue of Prosopis laegivata grown at the edge of a mine
tailing in San Luis Potosi, Mexico. Its cells were non-spore-forming rods,
showing catalase and oxidase activities and were able to grow in LB medium added
with 40 mM Cu(2+), 72 mM As(5+) and various other toxic elements. Anteiso-C15:0
(41.6 %), anteiso-C17:0 (30 %) and iso-C15:0 (9.5 %) were the major fatty acids.
MK-8(H2) (88.4 %) and MK-7(H2) (11.6 %) were the major menaquinones. The DNA G +
C content of the strain NM2E3(T) was 70.8 mol % (Tm). DNA-DNA hybridization
showed that the strain NM2E3(T) had 39.8, 21.7 and 20.3 % relatedness with B.
yomogidense JCM 17779(T), B. jeotgali JCM 18571(T) and B. salitolerans TRM 45(T),
respectively. Based on the phenotypic and genotypic analyses, the strain NM2E3(T)
(=CCBAU 101093(T) = HAMBI 3627(T) = LMG 8673(T)) is reported as a novel species
of the genus Brevibacterium, for which the name Brevibacterium metallicus sp.
nov., is proposed.
PMID- 26429722
TI - Metaboreflex activity in multiple sclerosis patients.
AB - PURPOSE: The muscle metaboreflex activation has been shown essential to reach
normal hemodynamic response during exercise. It has been demonstrated that
patients with multiple sclerosis (MS) have impaired autonomic functions and
cardiovascular regulation during exercise. However, to the best of our knowledge,
no previous research to date has studied the metaboreflex in MS patients. The
purpose of this study was to investigate the hemodynamic response to metaboreflex
activation in patients with MS (n = 43) compared to an age-matched, control group
(CTL, n = 21). METHODS: Cardiovascular response during the metaboreflex was
evaluated using the post-exercise muscle ischemia (PEMI) method and during a
control exercise recovery (CER) test. The difference in hemodynamics between the
PEMI and the CER test was calculated and this procedure allowed for the
assessment of the metaboreflex response. Hemodynamics was estimated by impedance
cardiography. RESULTS: The MS group showed a normal mean blood pressure (MBP)
response as compared to the CTL group (+6.5 +/- 6.9 vs. +8 +/- 6.8 mmHg,
respectively), but this response was achieved with an increase in systemic
vascular resistance, that was higher in the MS with respect to the CTL group
(+137.6 +/- 300.5 vs. -14.3 +/- 240 dyne . s(-1) cm(-5), respectively). This was
the main consequence of the MS group's incapacity to raise the stroke volume (
0.65 +/- 10.6 vs. +6.2 +/- 12.8 ml, respectively). CONCLUSION: It was concluded
that MS patients have an impaired capacity to increase stroke volume (SV) in
response to low level metaboreflex, even if they could sustain the MBP response
by vasoconstriction. This was probably a consequence of their chronic physical de
conditioning.
PMID- 26429723
TI - A slouched body posture decreases arm mobility and changes muscle recruitment in
the neck and shoulder region.
AB - PURPOSE: Long-term use of unfavorable postures, congenital deformations and
degenerative processes associated with aging or disease may generate an increased
thoracic curvature resulting in pain and disability. We wanted to examine whether
a slouched postural alignment with increased thoracic kyphosis changes the
shoulder kinematics and muscle activity in upper trapezius (UT), lower trapezius
(LT) and serratus anterior (SA) during arm elevation. The aim was to determine if
a slouched posture influences range of motion, muscle activation patterns,
maximal muscle activity and the total muscle work required when performing arm
elevations. METHOD: Twelve male subjects (23.3 +/- 1.5 years) performed maximum
arm elevations in upright and slouched postures. A combined 3D movement and EMG
system recorded arm movements and spine curvature simultaneously with EMG
activity in the UT, LT and SA. RESULTS: Slouched posture affected the
biomechanical conditions by significantly decreasing maximum arm elevation by ~15
degrees (p < 0.001) and decreasing arm movement velocity by ~8 % during
movements upwards (p < 0.001) and downwards (p = 0.034). The peak muscle activity
increased in all muscles: UT (p = 0.034, +32.3 %), LT (p = 0.001, +48.6 %) and SA
(p = 0.007, +20.9 %). The total muscle work increased significantly in the
slouched posture during movements upwards: UT (p = 0.003, +36.6 %), LT (p <
0.001, +89.0 %), SA (p = 0.002, +19.4 %) and downwards: UT (p = 0.012, +29.8 %)
and LT (p < 0.001, +122.5 %). CONCLUSION: An increased thoracic kyphosis was
found associated with marked increased physical costs when performing arm
movements. Hence, patients suffering from neck-shoulder pain and disability
should be investigated and treated for defective thoracic curvature issues.
PMID- 26429724
TI - GNL3 and SKA3 are novel prostate cancer metastasis susceptibility genes.
AB - Prostate cancer (PC) is very common in developed countries. However, the
molecular determinants of PC metastasis are unclear. Previously, we reported that
germline variation influences metastasis in the C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP)
mouse model of PC. These mice develop prostate tumors similar to a subset of poor
outcome, treatment-associated human PC tumors. Here, we used TRAMP mice to
nominate candidate genes and validate their role in aggressive human PC in PC
datasets and cell lines. Candidate metastasis susceptibility genes were
identified through quantitative trait locus (QTL) mapping in 201 (TRAMP *
PWK/PhJ) F2 males. Two metastasis-associated QTLs were identified; one on
chromosome 12 (LOD = 5.86), and one on chromosome 14 (LOD = 4.41). Correlation
analysis using microarray data from (TRAMP * PWK/PhJ) F2 prostate tumors
identified 35 metastasis-associated transcripts within the two loci. The role of
these genes in susceptibility to aggressive human PC was determined through in
silico analysis using multiple datasets. First, analysis of candidate gene
expression in two human PC datasets demonstrated that five candidate genes were
associated with an increased risk of aggressive disease and lower disease-free
survival. Second, four of these genes (GNL3, MAT1A, SKA3, and ZMYM5) harbored
SNPs associated with aggressive tumorigenesis in the PLCO/CGEMS GWAS of 1172 PC
patients. Finally, over-expression of GNL3 and SKA3 in the PC-3 human PC cell
line decreased in vitro cell migration and invasion. This novel approach
demonstrates how mouse models can be used to identify metastasis susceptibility
genes, and gives new insight into the molecular mechanisms of fatal PC.
PMID- 26429725
TI - Risk factors for renal dysfunction after total hip joint replacement; a
retrospective cohort study.
AB - BACKGROUND AND PURPOSE OF THE STUDY: Renal injury and dysfunction are serious
complications after major surgery, which may lead to increased morbidity and
mortality. The objective of our study was to identify the possible risk factors
for renal dysfunction after total hip joint replacement surgery. METHODS: A
retrospective study was conducted among 599 consecutive primary hip joint
replacements performed between January 2011 and December 2013. According to the
RIFLE criteria, increased postoperative serum creatinine was considered
indicative of postoperative renal injury. The Welch two-sample test, chi-square
test, and Fisher exact test were used for statistical analysis. RESULTS: Eighty
one patients (13.8%) had significant moderate or severe postoperative renal
dysfunction in which 10 patients (1.7%) acquired severe and permanent renal
impairment. CONCLUSION: We identified advanced age, hypertension, general
anesthesia, high ASA scores, low intra-operative systolic BP, and prophylactic
dicloxacillin as significant risk factors. Low baseline systolic BP, low baseline
diastolic blood pressure, and hip fracture diagnosis were independent risk
factors for postoperative increase in serum creatinine. Smoking, diabetes
mellitus, high BMI, gender, and duration of surgery were not identified as
significant risk factors.
PMID- 26429726
TI - Treatment outcomes for veterans with PTSD and substance use: Impact of specific
substances and achievement of abstinence.
AB - BACKGROUND: Scant longitudinal data exists about the interplay between specific
substances of abuse, the achievement of abstinence, and clinical outcomes in the
treatment of dually diagnosed Veterans with post-traumatic stress disorder
(PTSD). METHODS: As part of a national program evaluation, Veterans admitted from
the community to specialized intensive PTSD programs were assessed at intake and
4 months after discharge. Seven mutually exclusive groups were identified from
admission self-report data (N=22,948): no substance use, exclusive use of
alcohol, opiates, sedatives, cocaine, marijuana, and use of three or more
substances. Analysis of covariance, adjusting for potentially confounding
baseline variables was used to compare change among these seven groups in non
substance use outcomes (PTSD symptoms, violent behavior, suicidality, medical
problems, and employment). The effect of abstinence on specific groups was
evaluated as the interaction of group membership by abstinence. RESULTS: All
outcome measures except for employment showed significant improvement, with few
differences between the groups. Although rate of abstinence differed markedly
between the groups, abstinence achievement was associated with greater
improvement on all the outcomes except employment in every group. No significant
differences in the effect of abstinence across the substance abuse groups were
observed. CONCLUSION: The specific type of substance used prior to entry into
treatment among dually diagnosed PTSD patients seems to have limited effect on
treatment outcomes. However, attainment of abstinence at 4 months after
treatment, irrespective of the substances abused, was strongly associated with
improvement in PTSD symptoms, violence, suicidality and medical problems.
PMID- 26429727
TI - Maternal age and trajectories of cannabis use.
AB - BACKGROUND: Becoming a mother is a developmental transition that has been linked
to desistance from substance use. However, timing of motherhood may be a key
determinant of cannabis use in women, based on preliminary evidence from teenage
mothers. The goal of this study was to identify trajectories of maternal cannabis
use, and to determine if maternal age was associated with different trajectories
of use. METHODS: This prospective study examined 456 pregnant women recruited at
a prenatal clinic, ranging in age from 13 to 42 years. The women were interviewed
about their cannabis use 1 year prior to pregnancy and during each trimester of
pregnancy, and at 6, 10, 14, and 16 years post-partum. RESULTS: A growth mixture
model of cannabis use reported at each time point clearly delineated four groups:
non/unlikely to use, decreasing likelihood of use, late desistance, and
increasing likelihood/chronic use (Lo-Mendell-Rubin adjusted LRT test
statistic=35.7, p<.001). The youngest mothers were least likely to be in the
"non/unlikely to use" group. Younger maternal age also differentiated between
late desistance and increasing likelihood/chronic use, versus decreasing
likelihood of use post-partum. CONCLUSIONS: This is the first study to
demonstrate that younger mothers are more likely to use cannabis across 17 years,
including later desistance post-partum and increasing/chronic use. Other
substance use and chronic depressive symptoms were also associated with more
frequent use. These findings have implications for both prevention and treatment
of cannabis use in mothers.
PMID- 26429729
TI - Spirituality Moderates Hopelessness, Depression, and Suicidal Behavior among
Malaysian Adolescents.
AB - Suicide is an important public health problem for adolescents, and it is
essential to increase our knowledge concerning the etiology of suicide among
adolescent students. Therefore, this study was designed to examine the
associations between hopelessness, depression, spirituality, and suicidal
behavior, and to examine spirituality as a moderator between hopelessness,
depression, and suicidal behavior among 1376 Malaysian adolescent students. The
participants completed measures of depression, hopelessness, daily spiritual
experience, and suicidal behavior. Structural equation modeling indicated that
adolescent students high in hopelessness and depression, but also high in
spirituality, had less suicidal behavior than others. These findings reinforce
the importance of spirituality as a protective factor against hopelessness,
depression, and suicidal behavior among Malaysian adolescent students.
PMID- 26429728
TI - The selective dopamine D3 receptor antagonist, SR 21502, reduces cue-induced
reinstatement of heroin seeking and heroin conditioned place preference in rats.
AB - BACKGROUND: Because the role of dopamine (DA) D3 receptors has been investigated
primarily in relation to cocaine-related behaviors little is known of the role of
these receptors in heroin seeking. PURPOSES: To investigate the effect of the
selective DA D3 receptor antagonist, SR 21502, on cue-induced reinstatement of
heroin seeking and heroin conditioned place preference (CPP). METHODS: In
experiment 1, rats were trained to self-administer intravenous heroin for 15 days
followed by extinction. Following extinction animals were treated with one of
several SR 21502 doses (0, 7.5, 10 or 15mg/kg) and a cue-induced reinstatement
test was conducted. In experiment 2, animals were conditioned to experience
heroin in one compartment of a CPP apparatus and saline in the other. On the test
day animals were treated with 0, 3.75, 7.5, 10 or 15mg/kg of SR 21502 and tested
for their CPP. RESULTS: The results from experiment 1 showed a significant dose
related reduction in cue-induced reinstatement of active lever pressing in the
7.5 and 10mg groups and an absence of the reinstatement effect in the 15mg group.
In experiment 2, animals treated with vehicle or 3.75mg of SR 21502 showed
significant heroin place preferences but those treated with the higher doses
showed no CPP. CONCLUSIONS: Our findings suggest that DA D3 receptors play a
significant role in heroin approach behaviors driven by conditioned stimuli. As
such, we propose that SR 21502 holds potential as an effective
pharmacotherapeutic agent for relapse prevention and should be studied further.
PMID- 26429730
TI - Effect of Religious Beliefs on the Smoking Behaviour of University Students:
Quantitative Findings From Malaysia.
AB - The Malaysian official Islamic authorities have issued a "fatwa" (Islamic ruling)
regarding smoking practice which prohibits Muslims from smoking because of its
potential harm to health. Since the prevalence of smoking among Malaysian
students is high, this study was designed to explore the perceptions and opinions
of Malaysian Muslim students towards smoking in International Islamic University
of Malaysia. A prospective, cross-sectional study was conducted among School of
Science students in International Islamic University Malaysia. Convenience
sampling approach was used to recruit 323 students based on sample size
calculation. A content- and face-validated questionnaire was used to collect the
data from the participants. Non-smokers highly supported the fatwa on smoking
forbiddance than smokers (94 vs 64.3 %, p = 0.001). A significant proportion of
non-smokers believed that Islam prohibits smoking because of its potential harm
(94.9 vs 71.4 %, p = 0.001). Majority of smokers agreed that addiction is the
main barrier towards smoking cessation (78.6 vs 61.5 %, p = 0.019). The results
showed positive influences of Islamic beliefs on the non-smokers. Further studies
are required to validate these findings by surveying other universities of
Malaysia.
PMID- 26429732
TI - Biceps Femoris Architecture and Strength in Athletes with a Previous Anterior
Cruciate Ligament Reconstruction.
AB - PURPOSE: This study aimed to determine whether limbs with a history of anterior
cruciate ligament (ACL) injury reconstructed from the semitendinosus display
different biceps femoris long head (BFlh) architecture and eccentric strength,
assessed during the Nordic hamstring exercise, compared with the contralateral
uninjured limb. METHODS: The architectural characteristics of the BFlh were
assessed at rest and at 25% of a maximal voluntary isometric contraction (MVIC)
in the control group (n = 52) and in the group who had previous ACL injury (n =
15) using two-dimensional ultrasonography. Eccentric knee flexor strength was
assessed during the Nordic hamstring exercise. RESULTS: Fascicle length was
shorter (P = 0.001; d range, 0.90-1.31) and pennation angle (P range, 0.001
0.006; d range, 0.87-0.93) was greater in the BFlh of the ACL-injured limb
compared with those in the contralateral uninjured limb at rest and during a 25%
MVIC. Eccentric strength was lower in the ACL-injured limb when compared with the
contralateral uninjured limb. Fascicle length, MVIC, and eccentric strength were
not different between the left and right limb in the control group. CONCLUSIONS:
Limbs with a history of ACL injury reconstructed from the semitendinosus have
shorter fascicles and greater pennation angles in the BFlh compared with those of
the contralateral uninjured side. Eccentric strength during the Nordic hamstring
exercise of the ACL-injured limb is significantly lower than that of the
contralateral side. These findings have implications for ACL rehabilitation and
hamstring injury prevention practices, which should consider altered
architectural characteristics.
PMID- 26429731
TI - Double-Edged Roles of Nitric Oxide Signaling on APP Processing and Amyloid-beta
Production In Vitro: Preliminary Evidence from Sodium Nitroprusside.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is
thought to be caused in part by the age-related accumulation of amyloid-beta
(Abeta) in the brain. Recent findings have revealed that nitric oxide (NO)
modulates the processing of amyloid-beta precursor protein (APP) and alters Abeta
production; however, the previously presented data are contradictory and the
underlying molecular mechanisms are still incomplete. Here, using human SH-SY5Y
neuroblastoma cells stably transfected with wild-type APPwt695, we found that NO,
derived from NO donor sodium nitroprusside (SNP), bi-directionally modulates APP
processing in vitro. The data from ELISA and Western blot (WB) tests indicated
that SNP at lower concentrations (0.01 and 0.1 MUM) inhibits BACE1 expression,
thus consequently suppresses APP beta-cleavage and decreases Abeta production. In
contrast, SNP at higher concentrations (10 and 20 MUM) biases the APP processing
toward the amyloidogenic pathway as evidenced by an increased BACE1 but a
decreased ADAM10 expression, together with an elevated Abeta secretion. This bi
directional modulating activity of SNP on APP processing was completely blocked
by specific NO scavenger c-PTIO, indicating NO-dependent mechanisms. Moreover,
the anti-amyloidogenic activity of SNP is sGC/cGMP/PKG-dependent as evidenced by
its reversal by sGC/PKG inhibitions, whereas the amyloidogenic activity of SNP is
peroxynitrite-related and can be reversed by peroxynitrite scavenger uric acid.
In summary, these present findings predict a double-edged role of NO in APP
processing in vitro. Low (physiological) levels of NO inhibit the amyloidogenic
processing of APP, whereas extra-high (pathological) concentrations of NO favor
the amyloidogenic pathway of APP processing. This preliminary study may provide
further evidence to clarify the molecular roles of NO and NO-related signaling in
AD and supply potential molecular targets for AD treatment.
PMID- 26429733
TI - Seasonal Variation in Children's Physical Activity and Sedentary Time.
AB - PURPOSE: Understanding seasonal variation in physical activity is important for
informing public health surveillance and intervention design. The aim of the
current study was to describe seasonal variation in children's objectively
measured physical activity and sedentary time. METHODS: Data are from the UK
Millennium Cohort Study. Participants were invited to wear an accelerometer for 7
d on five occasions between November 2008 and January 2010. Outcome variables
were sedentary time (<100 counts per minute, min.d(-1)) and moderate to vigorous
physical activity (MVPA) (>2241 counts per minute, min.d(-1)). The season was
characterized using a categorical variable (spring, summer, autumn, or winter)
and a continuous function of day of the year. Cross-classified linear regression
models were used to estimate the association of each of these constructs with the
outcome variables. Modification of the seasonal variation by sex, weight status,
urban/rural location, parental income, and day of the week (weekday/weekend) was
examined using interaction terms in regression models. RESULTS: At least one wave
of valid accelerometer data was obtained from 704 participants (47% male;
baseline age, 7.6 (0.3) yr). MVPA was lower in autumn and winter relative to
spring, with the magnitude of this difference varying by weekday/weekend, sex,
weight status, urban/rural location, and family income (P for interaction <0.05
in all cases). Total sedentary time was greater in autumn and winter compared
with spring; the seasonal effect was stronger during the weekend than during the
weekday (P for interaction <0.01). CONCLUSIONS: Lower levels of MVPA and elevated
sedentary time support the implementation of intervention programs during autumn
and winter. Evidence of greater seasonal variation in weekend behavior and among
certain sociodemographic subgroups highlights targets for tailored intervention
programs.
PMID- 26429734
TI - The Effect of Heterozygosity for the ACTN3 Null Allele on Human Muscle
Performance.
AB - alpha-Actinin-3 is primarily expressed in fast (Type II) fibers in the human
skeletal muscle. Over 70% of the global population has at least one copy of a
loss of function allele because of a premature stop codon in the ACTN3 gene
(R577X). Homozygosity for this variant (577XX) occurs in approximately 16% of
humans worldwide and results in complete alpha-actinin-3 deficiency, which is
detrimental to sprint/power performance and alters adaptation to changing
physical demands. The functional implications of alpha-actinin-3 deficiency have
been the subject of over 90 studies; however, the effect of heterozygosity for
the ACTN3 null allele is not well documented or understood. PURPOSE: We reviewed
the literature to focus on the most common ACTN3 genotype (577RX) and its effect
on human muscle performance. Specifically, we aimed to determine whether the
ACTN3 X allele exerts its effect on human performance only when two copies are
present (i.e., in an autosomal recessive fashion). RESULTS: Across a spectrum of
conditions, three genotype models (additive, dominant, and recessive) were
reported. Most studies assessing healthy adults demonstrated that 577RX
heterozygotes performed intermediately (additive model) and/or similarly to the
RR genotypes (recessive model). Other studies, (aging, disease/injury, elite
sprint performance) showed no definitive genetic model. CONCLUSIONS: Assessment
of the biological link between dosage, regulation, and function for each ACTN3
genotype is required to improve our understanding of its functional effect and
biological penetrance in healthy, aging, and disease populations.
PMID- 26429735
TI - A case control study of sarcosine as an early prostate cancer detection
biomarker.
AB - BACKGROUND: Sarcosine has been investigated as a prostate cancer biomarker with
mixed results concerning its predictive power. We performed a case-control
evaluation of the predictive value of serum sarcosine for early detection in a
population-based cohort of men undergoing prostate-specific antigen (PSA)
screening. METHODS: For analysis we used 251 cancer cases and 246 age-matched non
cancer cases from the San Antonio Biomarkers Of Risk (SABOR) screening study. For
cancer cases, pre-diagnostic serum was utilized for sarcosine measurement.
Controls were defined as men who had been followed at least for 5 years on study
with no prostate cancer diagnosis; sarcosine was measured on the initial baseline
serum. HPLC-electrospray ionization mass spectrometry was used for serum
sarcosine quantification. The association of sarcosine with prostate cancer was
assessed using area underneath the receiver-operating characteristic curve (AUC),
and logistic regression adjusting for PSA, digital rectal exam, family history,
age, race, and history of a prior negative biopsy. Among cancer cases, nominal
logistic regression was used for the association of sarcosine with Gleason grade.
RESULTS: Sarcosine levels were overlapping between the prostate cancer cases
(median 15.8 uM, range 6.2 to 42.5 uM) and controls (median 16.2 uM, range 6.4 to
53.6 uM). The AUC of sarcosine was not statistically different from random chance
either for participants with any PSA value (52.2 %) or those with PSA values in
the range of 2 to 10 ng/mL (54.3 %). Sarcosine was not predictive of Gleason
score and added no independent predictive power to standard prostate cancer risk
factors for detection of prostate cancer (all p-values > 0.05). CONCLUSIONS:
Serum sarcosine should not be pursued further as a marker for the early detection
of prostate cancer.
PMID- 26429736
TI - Utility of immune response-derived biomarkers in the differential diagnosis of
inflammatory disorders.
AB - Differentiating between inflammatory disorders is difficult, but important for a
rational use of antimicrobial agents. Biomarkers reflecting the host immune
response may offer an attractive strategy to predict the etiology of an
inflammatory process and can thus be of help in decision making. We performed a
review of the literature to evaluate the diagnostic value of inflammatory
biomarkers in adult patients admitted to the hospital with suspected systemic
acute infections. Elevated procalcitonin (PCT) concentrations indicate a
bacterial infection in febrile patients with an auto-immune disease, rather than
a disease flare. CD64 expression on neutrophils can discriminate between non
infectious systemic inflammation and sepsis, and limited evidence suggests the
same for decoy receptor 3. PCT is useful for both diagnosing bacterial infection
complicating influenza and guiding antibiotic treatment in lower respiratory
tract infections in general. In undifferentiated illnesses, increased CD35
expression on neutrophils distinguishes bacterial from viral infections. Compared
to bacterial infections, invasive fungal infections are characterized by low
concentrations of PCT. No biomarker predicting a specific infecting agent could
be identified.
PMID- 26429737
TI - A multidisciplinary management of a type III dens invaginatus in a maxillary
permanent canine.
AB - BACKGROUND: Dens invaginatus affects 0.3-10% of the population; however, few
reports document its occurrence in maxillary canines. Management of associated
periradicular infections is often challenging. The benefits of computed
tomography are well documented in these situations, providing greater clinical
information for diagnosis, prognosis and practical management. Many previous
reports in the literature utilise this technology but often focus on an
endodontic management approach. CASE REPORT: Details of the treatment of a
complex type III invagination affecting a maxillary canine, combined with
hypodontia and malocclusion is described. Endodontic treatment was deemed
inappropriate resulting in extraction of the invaginated canine. The
multidisciplinary planning and approach, highlighted the need for close teamwork,
shared care and a patient-centred approach. FOLLOW-UP: A 5-year follow-up and
review recorded a successful outcome. CONCLUSIONS: This case reinforces the
importance of careful investigation and planning in ensuring an optimal outcome
when addressing multiple dental anomalies. Extensive consideration of the initial
treatment strategy is required, coupled with evaluation of the outcome and
longevity of any potential treatment modality to be employed. The consideration
of inevitable future restorative treatment is fundamental, highlighting the
importance of multidisciplinary planning at diagnosis. Moreover, orthodontic,
aesthetic, behavioural and/or social factors may further complicate management in
adolescents.
PMID- 26429738
TI - Infrared and Fluorescence Spectroscopic Investigations of the Acyl Surface
Modification of Hydrogel Beads for the Deposition of a Phospholipid Coating.
AB - The scaffolded vesicle has been employed as an alternative means of developing
natural model membranes and envisioned as a potential nutraceutical transporter.
Furthering the research of the scaffolded vesicle system, a nucleophilic
substitution reaction was implemented to form an ester linkage between palmitate
and terminal hydroxyl groups of dextran in order to hydrophobically modify the
hydrogel scaffold. An average tilt angle of 38 degrees of the hydrophobic
palmitate modifying layer on the surface of the hydrogel was determined from
dichroic ratios obtained from infrared spectra collected in the attenuated total
reflection (ATR) configuration. ATR-IR studies of the DMPC-coated acylated
hydrogel demonstrated that the hydrocarbon chains of the DMPC coating was similar
to those of the DMPC bilayers and that the underlying palmitate layer had a
negligible effect on the average tilt angle (26 degrees ) of the DMPC coating.
The permeability of this acylated hydrogel was investigated with fluorescence
spectroscopy and the terbium/dipicolinic acid assay. The hydrophobic modification
on the surface of the hydrogel bead allowed for an efficient deposition of a DMPC
layer that served as an impermeable barrier to terbium efflux. About 72% of DMPC
coated acylated hydrogel beads showed ideal barrier properties. The remaining 28%
were leaking, but the half-life of terbium efflux of the DMPC-coated acylated
hydrogel was increasing, and the total amount of leaked terbium was decreasing
with the incubation time. The half-life time and the retention were considered a
marked improvement relative to past scaffolded vesicle preparations. The process
of acylating hydrogel beads for efficient DMPC deposition has been identified as
another viable method for controlling the permeability of the scaffolded vesicle.
PMID- 26429740
TI - Virus-Specific Cellular Response in Hepatitis C Virus Infection.
AB - Studies performed on chimpanzees and humans have revealed that strong,
multispecific and sustained CD4(+) and CD8(+) T cell immune responses is a major
determinant of hepatitis C virus (HCV) clearance. However, spontaneous
elimination of the virus occurs in minority of infected individuals and cellular
response directed against HCV antigens is not persistent in individuals with
chronic infection. This review presents characteristics of the HCV-specific T
cell response in patients with different clinical course of infection, including
acute and chronic infection, persons who spontaneously eliminated HCV and non
infected subjects exposed to HCV. Detection of HCV-specific response, especially
in non-infected subjects exposed to HCV, may be indicative of HCV prevalence in
population and rate of spontaneous viral clearance. Understanding the mechanisms
and role of HCV-specific cellular immune response would contribute to better
understanding of HCV epidemiology, immunopathogenesis and may help to design an
effective vaccine.
PMID- 26429739
TI - Cripto-1 ablation disrupts alveolar development in the mouse mammary gland
through a progesterone receptor-mediated pathway.
AB - Cripto-1, a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family,
is critical for early embryonic development. Together with its ligand Nodal,
Cripto-1 has been found to be associated with the undifferentiated status of
mouse and human embryonic stem cells. Several studies have clearly shown that
Cripto-1 is involved in regulating branching morphogenesis and epithelial
mesenchymal transition of the mammary gland both in vitro and in vivo and
together with the cofactor GRP78 is critical for the maintenance of mammary stem
cells ex vivo. Our previous studies showed that mammary-specific overexpression
of human Cripto-1 exhibited dramatic morphological alterations in nulliparous
mice mammary glands. The present study shows a novel mechanism for Cripto-1
regulation of mammary gland development through direct effects on progesterone
receptor expression and pathways regulated by progesterone in the mammary gland.
We demonstrate a strict temporal regulation of mouse Cripto-1 (mCripto-1)
expression that occurs during mammary gland development and a stage-specific
function of mCripto-1 signaling during mammary gland development. Our data
suggest that Cripto-1, like the progesterone receptor, is not required for the
initial ductal growth but is essential for subsequent side branching and
alveologenesis during the initial stages of pregnancy. Dissection of the
mechanism by which this occurs indicates that mCripto-1 activates receptor
activator NF-kappaB/receptor activator NF-kappaB ligand, and NF-kappaB signaling
pathways.
PMID- 26429741
TI - Value of a Joint Cardiac Surgery-Cardiac Electrophysiology Approach to Lead
Extraction.
AB - We report three cases of vascular injury during laser lead extractions, requiring
urgent surgical correction. Immediate sternotomy and cardiopulmonary bypass were
possible because of an institutional collaboration where cardiac surgeon and
cardiac electrophysiologist jointly perform these cases, and all patients
survived. We propose this joint approach is ultimately the best option for
patients undergoing lead extraction.
PMID- 26429742
TI - Outcome of adenotonsillectomy for children with sleep apnea.
AB - BACKGROUND AND OBJECTIVES: The prevalence of obstructive sleep apnea syndrome is
about 1%-4.9% in children aged 2-18 years. This is a prospective study carried
out to evaluate the role of adenotonsillectomy (AT) in pediatric sleep apnea.
METHODS: Fifty children aged less than 15 years presenting with the chief
complaints of snoring, mouth breathing, recurrent upper respiratory infections,
and adenotonsillar hypertrophy were included in the study. Physical examination
included body mass index (BMI) z-score, orodental and nasal examination, modified
Mallampati scoring; whole-night level I polysomnography was conducted and
repeated after three to six months of AT. RESULTS: The mean preoperative BMI z
score was -0.76, which improved significantly to -0.15 (p < 0.001) after AT. A
negative correlation was seen between respiratory distress index (RDI) and pre
surgery BMI z-score. As per pre-operative RDI, OSA was classified mild in 6.7%
children (31.1% as per apnea-hypopnea index [AHI]), moderate in 35.6% (31.1% as
per AHI), and severe in 57.8% (37.8% as per AHI). The average RDI value reduced
significantly from 16.2 +/- 10.7 to 6.46 +/- 4.8 (p < 0.001) and AHI from 8.5 (SD
+/- 5.7) to 1.3 (SD +/- 1) post-operatively. Only 6.7% children could be cured
with surgery, of whom none belonged to moderate or severe category. Multivariate
analysis shows that initial severity of disease, modified Mallampati scores III
and IV, high-arched palate, and age above eight years were associated with
significant residual disease after AT. CONCLUSION: AT was associated with a
statistically significant change in RDI and AHI. However, complete resolution of
OSA could be seen in a small percentage of patients with a mild degree of
disease.
PMID- 26429743
TI - Pupillometric findings in children with obstructive sleep apnea.
AB - BACKGROUND: Obstructive sleep apnea (OSA) leads to intermittent hypoxia,
activation of the sympathetic nervous system, and eventually cardiovascular
morbidity. Alterations in autonomic nervous system (ANS) tone and reflexes are
likely to play major roles in OSA-associated morbidities, and have been
identified in a subset of children with OSA. OBJECTIVES: To evaluate whether
pupillometry, a noninvasive and rapid bedside test for the assessment of
autonomic nervous system dysfunction (ANS), would detect abnormal ANS function in
children with OSA. METHODS: Children ages 2-12 years underwent polysomnography
(PSG), and were divided based on PSG findings into two groups; Habitual Snorers
(HS; AHI < 1 h/TST, n = 17) and OSA (AHI > 1 h/TST, n = 49), the latter then sub
divided into AHI severity categories (>1 but <5, >5 but <10, and >10 h/TST).
Pupillometric measurements were performed during the clinic visit in a dark room
using an automated pupillometer device. RESULTS: A total of 66 subjects with a
mean age of 7.3 +/- 2.6 years were recruited. There were no statistically
significant differences between any of the groups, even when comparing severe OSA
(n = 15) and HS in any of the measures related to pupillary reflexes. However,
mild, yet significant increases in systolic blood pressure and morning plasma
norepinephrine levels were detected in the severe OSA group. CONCLUSION: Although
ANS perturbations are clearly present in a proportion of children with OSA,
particularly those with severe disease, pupillary responses do not appear to
provide a sensitive method for the detection of ANS dysfunction in OSA children.
PMID- 26429744
TI - Association between sleep and working memory in children with ADHD: a cross
sectional study.
AB - OBJECTIVE/BACKGROUND: This study aimed to examine the relationship between sleep
problems and working memory in children aged 5-13 years with attention
deficit/hyperactivity disorder (ADHD). PATIENTS/METHODS: Children with ADHD were
recruited into a randomized controlled trial from 21 paediatric practices in VIC,
Australia. Cross-sectional data for intervention and control children were pooled
at 6 months post randomization for the current analyses (n = 189). Children who
met the Diagnostic Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)
criteria for ADHD and had a parent-reported moderate/severe sleep problem that
fulfilled diagnostic criteria for a behavioural sleep disorder were recruited
into the study. Sleep was assessed by detailed parent (Children's Sleep Habits
Questionnaire) and self-reports (Self-Sleep Report). Working memory was measured
using the Working Memory Test Battery for Children (low and very low working
memory defined as <25th and <10th percentiles, respectively). Analyses were
adjusted for child age and gender, internalizing and externalizing comorbidities,
and socio-economic status. RESULTS: Self-reported sleep problem severity was
associated with poorer working memory; for each standard deviation increase in
self-reported sleep problems, working memory scores decreased by -3.8 points (95%
confidence interval (CI): -6.7, -0.8; p = 0.01). There was some evidence that
self-reported sleep problems were associated with low (p = 0.06) and very low
working memory (p = 0.01). There was minimal evidence that parent-reported sleep
problems were associated with poorer working memory with the exception of bedtime
resistance problems. CONCLUSIONS: Behavioural sleep problems and working memory
are associated in children with ADHD, particularly when sleep is assessed by self
report.
PMID- 26429746
TI - Empirical validation of a short version of the Adolescent Sleep-Wake Scale using
a sample of ethnically diverse adolescents from an economically disadvantage
community.
AB - OBJECTIVE: There is a need for brief, psychometrically sound instruments to
assess adolescent sleep, particularly for ethnic minority and economically
disadvantaged adolescents. A 10-item short version of the Adolescent Sleep-Wake
Scale was recently proposed based upon exploratory factor analysis with primarily
Caucasian healthy adolescents from middle- to high-income families. The aim of
this study was to expand the utility of the short version of the Adolescent Sleep
Wake Scale by investigating the empirical and construct validity of the measure
on an ethnically diverse sample of adolescents from an economically disadvantaged
community. MATERIALS AND METHODS: Participants included 467 adolescents (40%
African American, 35.5% Caucasian, 16.5% Latino, and 7.9% multiethnic), aged 12
18 years (mean = 15.27 years, SD = 1.96 years), who completed the Adolescent
Sleep-Wake Scale. A confirmatory factor analysis (CFA) was conducted with Mplus 7
based on the three-factor solution proposed by Essner et al. (2014). RESULTS: CFA
indicated that the three-factor structure was a good fit for the data (chi(2)
(29) = 52.053, p = 0.005, root mean square error of approximation (RMSEA) = 0.04,
CFI = 0.98, TLI = 0.96, standardized root mean residuals (SRMR) = 0.03), and
factor loadings for each item were >0.40. Cronbach's alphas by ethnicity
indicated that the scale has acceptable reliability (0.70 <= alpha <= 0.90) for
African American, Caucasian, and multiethnic adolescents, but not for Latino
adolescents. CONCLUSION: Our results support the use of the Adolescent Sleep-Wake
Scale short form for the majority of ethnic minority and economically
disadvantaged adolescents.
PMID- 26429747
TI - Poor sleep and neurocognitive function in early adolescence.
AB - BACKGROUND: Evidence regarding the associations between sleep duration and
quality, and neurocognitive function in adolescents remains scanty. This study
examined the associations in early adolescence between: sleep duration;
efficiency; fragmentation; wake-after-sleep-onset (WASO); catch-up sleep;
intelligence; memory; and executive function, including attention. METHODS: This
study included 354 girls and boys with a mean age 12.3 years (SD = 0.5) from a
birth cohort born in 1998. Sleep was measured with accelerometers for an average
of eight nights. Cognitive function was evaluated with subtests from the Wechsler
Intelligence Scale for Children-III (WISC-III), the Developmental
Neuropsychological Assessment 2 (NEPSY-2), the Wisconsin Card Sorting Task
(WCST), Conners' Continuous Performance Task (CPT), and the Trail Making Test
(TMT). RESULTS: In girls, a higher WASO and fragmentation index were associated
with poorer executive functioning (higher number of perseverative errors in the
WCST), and longer catch-up sleep was associated with longer reaction times and
better performance in one verbal intelligence test (Similarities subtest of the
WISC-III). In boys, shorter sleep duration, lower efficiency, higher WASO, higher
sleep fragmentation and shorter catch-up sleep were associated with lower
executive functioning (more commission errors, shorter reaction times, and had
lower D Prime scores in CPT). CONCLUSIONS: In adolescent girls, poorer sleep
quality was only weakly associated with poorer executive functioning, while in
boys, poorer sleep quantity and quality were associated with an inattentive
pattern of executive functioning. The amount of catch-up sleep during weekends
showed mixed patterns in relation to neurocognitive function.
PMID- 26429748
TI - The interactive effects of nocturnal sleep and daytime naps in relation to serum
C-reactive protein.
AB - BACKGROUND AND AIM: C-reactive protein (CRP) is a general marker of inflammation
that has been differentially linked with sleep. Elevated CRP (ie, high
inflammation) has been associated with either short/insufficient sleep duration
or long sleep duration, both, or neither. Daytime napping has also been tied to
increased and decreased inflammation. We attempted to unify these findings by
examining the relationship between CRP and sleep duration in conjunction with
napping in a healthy young adult cohort. PARTICIPANTS: Participants were young
adults (mean age = 29.05 years, n = 2147) from the National Longitudinal Study of
Adolescent Health (Add Health) cohort, a nationally representative longitudinal
sample. METHODS/RESULTS: Analysis of covariance (ANCOVA) tests examined whether
self-reported sleep duration (short, medium, or long) and nap frequency (none-few
days/week; most days/week; every day) interacted in relation to CRP. Standard
covariates (ie, age, gender, race/ethnicity, body mass index, physical activity,
depression, snoring, systolic blood pressure, clinical symptoms, and household
income) were used. There was a linear increase in CRP with increased napping
[contrast estimate = 0.265, 95% confidence interval (CI) (0.045-0.485), P =
0.018]. There was also an interaction between sleep duration and napping
frequency in relation to CRP (F4,2128 = 2.90, P = 0.021). Inflammation differed
between nap groups within the long and short sleep groups. CONCLUSIONS: Our
results suggest that increased napping is an independent predictor of
inflammation in young adults. These results also provide evidence for interactive
effects of inflammation, nocturnal sleep, and daytime naps. Our findings confirm
that excess sleep, insufficient sleep, frequent napping, and infrequent napping
can all be linked with elevated CRP, but these relationships depend on both
nocturnal and daytime sleep patterns. These analyses will guide future work to
more specifically examine sleep-inflammation processes and directionality.
PMID- 26429745
TI - Infarct location and sleep apnea: evaluating the potential association in acute
ischemic stroke.
AB - BACKGROUND: The literature about the relationship between obstructive sleep apnea
(OSA) and stroke location is conflicting with some studies finding an association
and others demonstrating no relationship. Among acute ischemic stroke patients,
we sought to examine the relationship between stroke location and the prevalence
of OSA; OSA severity based on apnea-hypopnea index (AHI), arousal frequency, and
measure of hypoxia; and number of central and obstructive respiratory events.
METHODS: Data were obtained from patients who participated in a randomized
controlled trial (NCT01446913) that evaluated the effectiveness of a strategy of
diagnosing and treating OSA among patients with acute ischemic stroke and
transient ischemic attack. Stroke location was classified by brain imaging
reports into subdivisions of lobes, subcortical areas, brainstem, cerebellum, and
vascular territory. The association between acute stroke location and
polysomnographic findings was evaluated using logistic regression for OSA
presence and negative binomial regression for AHI. RESULTS: Among 73 patients
with complete polysomnography and stroke location data, 58 (79%) had OSA. In
unadjusted models, no stroke location variable was associated with the prevalence
or severity of OSA. Similarly, in multivariable modeling, groupings of stroke
location were also not associated with OSA presence. CONCLUSIONS: These results
indicate that OSA is present in the majority of stroke patients and imply that
stroke location cannot be used to identify a group with higher risk of OSA. The
results also suggest that OSA likely predated the stroke. Given this high overall
prevalence, strong consideration should be given to obtaining polysomnography for
all ischemic stroke patients.
PMID- 26429749
TI - Actigraphic and self-reported sleep quality in women: associations with ovarian
hormones and mood.
AB - BACKGROUND: Sleep and mood disturbances in women have often been linked to the
menstrual cycle, implying an ovarian hormonal causation. However, most studies in
this area have used self-reported menstrual cycle phase rather than direct
measurement of ovarian hormone concentrations. Further, many studies have focused
primarily on peri- and postmenopausal populations reporting clinical sleep
difficulty. In this study, we examined the associations among sleep quality,
mood, and ovarian hormone concentration in a random sample of community-dwelling,
nonclinical women of reproductive age. METHODS: Our sample consisted of 19 non
help-seeking women aged 18-43 years, each contributing an average of 39.5 nights
of data. Over the 42 days of the study, we collected self-reported and
actigraphic sleep-quality data, concentrations of urinary estrogen and
progesterone metabolites (estrone-3-glucuronide (E1G) and pregnanediol-3
glucuronide [PdG], respectively), and daily mood ratings. Linear-mixed models
were used to estimate associations, clustering longitudinal observations by the
participant. RESULTS: We found a significant positive association between Sleep
Efficiency and E1G, and a significant negative association between Sleep
Efficiency and PdG. Otherwise, the self-reported and actigraphic sleep measures
were not associated with ovarian hormone concentrations. Self-reported sleep was
strongly associated with mood, whereas actigraphic sleep was associated with only
two of the 11 individual mood items, "Feeling on Top of Things" and "Difficulty
Coping." CONCLUSIONS: In this community sample of women of reproductive age,
ovarian hormones play little, if any, role in day-to-day sleep quality. Our
findings additionally highlight the different associations that self-reported and
actigraphic sleep show with hormones and mood.
PMID- 26429750
TI - Associations between poor sleep quality and different measures of obesity.
AB - OBJECTIVE: Poor sleep may be a risk factor for obesity. Previous studies have
mainly investigated the effects of sleep duration on body mass index, but
research considering overall sleep quality and other anthropometric measures is
scarce. The aim of this study was to examine the association between sleep
quality and different measures of obesity (general obesity, abdominal obesity,
body composition) in a population-based sample of adults. METHODS: The study
included 753 participants aged 35-65 years from the BiDirect Study, conducted in
Munster, Germany. Participants completed the Pittsburgh Sleep Quality Index
(PSQI) on sleep characteristics. Weight, height, and waist circumference were
measured by trained study nurses. Body composition (fat mass and fat-free mass)
was assessed using bioelectrical impedance analysis. The cross-sectional
relationship between sleep quality and measures of obesity was investigated using
logistic regression analysis. RESULTS: Among the participants, 65.3% reported
good (PSQI <= 5) and 34.7% poor (PSQI > 5) sleep quality. We observed a
significant association of poorer sleep quality assessed by the continuous PSQI
score with general obesity and high body fat (for both, odds ratio = 1.07, 95%
confidence interval = 1.01-1.13), adjusted for socio-demographic and lifestyle
factors. Further adjustment for depressive symptoms and somatic comorbidities
attenuated the relationship. The observed association was mainly driven by the
PSQI components sleep latency, sleep disturbances, and daytime dysfunction.
CONCLUSIONS: The present study suggests that poor sleep quality may predict
obesity and high body fat mass among adults. However, a causal relationship still
has to be confirmed by prospective studies with objective measurements of sleep
and obesity.
PMID- 26429751
TI - Putting the periodicity back into the periodic leg movement index: an alternative
data-driven algorithm for the computation of this index during sleep and
wakefulness.
AB - OBJECTIVE: To evaluate an alternative index for periodic leg movements during
sleep (PLMS) and wakefulness (PLMW) expected to be similar to the standard index
when leg movement activity is genuinely periodic, but significantly lower when
periodicity is low. SUBJECTS AND METHODS: One-hundred-and-seven subjects with
restless legs syndrome (RLS) were retrospectively identified and included (47
males, 60 females, mean age 56.9 years), along with 63 controls (33 males, 30
females, 42.2 years). Night-to-night variability was analysed in a subgroup of 17
subjects with RLS. PLMW were evaluated in a subgroup of 66 RLS subjects. Two
'alternative' PLMS/PLMW indices were calculated: one increased the lower limit of
the inter-movement intervals from 5 to 10 s ('Alt1') and another additionally
considered only series not interrupted by LMs with a short inter-movement
interval ('Alt2'). RESULTS: Despite a high correlation between methods, only the
Alt2 algorithm provided significantly different results, with PLMS/PLMW indices
being consistently lower than those provided by the other two methods. The
difference was more evident in the controls and during wakefulness, when
periodicity was lower. The difference between the Alt2 and the standard PLMS
index showed a significantly negative correlation with the Periodicity Index.
Night-to-night variability was similar for all PLMS indices and significantly
higher than the variability seen in the Periodicity Index. CONCLUSION: This
methodological study introduces an alternative to the standard PLMS/PLMW indices,
initiating the validation process for a new way of computing the PLMS/PLMW index,
more adherent to the parameters that allows a reliable evaluation of their
periodicity.
PMID- 26429753
TI - Effect of melatonin on sleep disorders in a monkey model of Parkinson's disease.
AB - OBJECTIVES: To evaluate and compare the effects of melatonin and levodopa (L
dopa) on sleep disorders in a monkey model of Parkinson's disease. MATERIALS AND
METHODS: The daytime and nighttime sleep patterns of four macaques that were
rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine (MPTP) were recorded using polysomnography in four conditions:
at baseline, during the parkinsonian condition; after administration of L-dopa,
and after administration of a combination of melatonin with L-dopa. RESULTS: It
was confirmed that MPTP intoxication induces sleep disorders, with sleep episodes
during daytime and sleep fragmentation at nighttime. L-dopa treatment
significantly reduced the awake time during the night and tended to improve all
other sleep parameters, albeit not significantly. In comparison to the
parkinsonian condition, combined treatment with melatonin and L-dopa
significantly increased total sleep time and sleep efficiency, and reduced the
time spent awake during the night in all animals. A significant decrease in sleep
latencies was also observed in three out of four animals. Compared with L-dopa
alone, combined treatment with melatonin and L-dopa significantly improved all
these sleep parameters in two animals. On the other hand, combined treatment had
no effect on sleep architecture and daytime sleep. CONCLUSION: These data
demonstrated, for the first time, objective improvement on sleep parameters of
melatonin treatment in MPTP-intoxicated monkeys, showing that melatonin treatment
has a real therapeutic potential to treat sleep disturbances in people with
Parkinson's disease.
PMID- 26429752
TI - Prevalence and associations of respiratory-related leg movements: the MrOS sleep
study.
AB - OBJECTIVES: Obstructive respiratory events often terminate with an associated
respiratory-related leg movement (RRLM). Such leg movements are not scored as
periodic leg movements (periodic limb movements during sleep, PLMS), although the
criteria for distinguishing RRLM from PLMS differ between the American Academy of
Sleep Medicine (AASM) and the World Association of Sleep Medicine (WASM)/
International Restless Legs Syndrome Study Group (IRLSSG) scoring manuals. Such
LMs may be clinically significant in patients with obstructive sleep apnea (OSA).
The prevalence and correlation of RRLM in men with OSA were examined. METHODS: A
case-control sample of 575 men was selected from all men with an apnea-hypopnea
index (AHI, >=3% desaturation criteria) >= 10 and good data from piezoelectric
leg movement sensors at the first in-home sleep study in the MrOS cohort (mean
age = 76.8 years). Sleep studies were rescored for RRLMs using five different
RRLM definitions varying in both latency of leg movement onset from respiratory
event termination and duration of the leg movement. The quartile of RRLM% (the
number of RRLM/the number of hypopneas + apneas) was derived. RESULTS: The
nonparametric densities of RRLM% were most influenced by alterations in the
latency rather than the duration of the LM. The most liberal RRLM definition
(latency 0-5 s, duration 0.5-10 s) led to a median RRLM% of 23.4 (interquartile
range 12.41, 37.12) in this sample. The average AHI and arousal index increased
as the quartile of RRLM% increased, as well as the prevalence of chronic
obstructive pulmonary disease (COPD). The prevalence of those with a history of
hypertension decreased as RRLM% increased. The non-Caucasian race was associated
with lower RRLM%. CONCLUSION: Within an elderly sample with moderate to severe
OSA, piezoelectric-defined RRLM% is associated with a number of sleep-related and
demographic factors. Further study of the optimal definition, predictors, and
consequences of RRLM is warranted.
PMID- 26429754
TI - Natural course of restless legs syndrome/Willis-Ekbom disease: long-term
observation of a large clinical cohort.
AB - OBJECTIVE: Although restless legs syndrome (RLS)/Willis-Ekbom disease (WED) is a
common neurological disorder, data on the long-term course and management of the
disease are scarce. The aim of the current study was to extend the knowledge on
the long-term clinical course and treatment outcome of RLS/WED. METHODS: In this
retrospective analysis, we performed a chart review of consecutive visits of 160
patients with definite RLS/WED from the RLS/WED database of the Innsbruck Medical
University. RESULTS: A total of 160 patients (58.8% female, aged 58.9 years,
range 21.5-86.8 years) met inclusion criteria of two or more visits during a
follow-up of at least five years. The duration of the observational period was
8.1 +/- 2.9 years. During the observational period, the percentage of treated
patients increased (first vs last visit: 67.5% vs 77.5%). Of the patients, 59.4%
had one or more switches of medication. Overall the RLS/WED severity, evaluated
using a combined severity score (CSS) ranging from 1 to 5, decreased between the
first and last visits (median [range], first visit: 3 [1-5] vs last visit 2.5 [1
5]; p <0.001). Symptoms improved in 55.0% of patients, worsened in 10.6%, and
remained unchanged in 34.4% during the observational period. Augmentation of
RLS/WED occurred in 42 patients (13/42 as the presenting cause; 29/42 occurring
during treatment after 4.1 years). The annual rate of augmentation for subjects
on dopaminergic medication was 8.1%. CONCLUSIONS: Our data suggest that, with the
possibility of regular treatment adjustments, RLS/WED remains treatable in the
majority of patients over years. Nevertheless, in this study, despite the overall
decreased severity, RLS symptoms remained unchanged or worsened in 45% of the
patients during the observational period.
PMID- 26429755
TI - Sleep-wake habits and circadian preference in Mexican secondary school.
AB - OBJECTIVE: The current study aimed to determine the differences between sleep
wake habits and circadian preference in Mexican adolescents attending classes at
a morning shift or an afternoon shift. METHODS: The sample consisted of 568
students of a secondary school in Reynosa, northeastern Mexico, of whom 280 were
boys and 288 were girls (mean age 14.08 +/- 0.72 years, age range 13-16 years).
In the morning shift, 287 students attend classes on a schedule from 7:30 to
13:00 and the afternoon shift, 281 students, on a schedule from 13:20 to 19:00.
Students completed a general information questionnaire, the Sleep Timing
Questionnaire and the Spanish version of the Morningness-Eveningness
Questionnaire. RESULTS: The adolescents who attended the morning shift had
earlier bedtime and waking time, but shorter sleep duration than those who
attended the afternoon shift. Those oriented to eveningness had later bedtime,
waking time, and a shorter sleep duration than those oriented to morningness. Two
interactions were found between school shift and chronotype. First, with regard
to waking time during weekdays, students who attended the afternoon shift and
were oriented to eveningness woke up later than those who attended the morning
shift and were oriented to eveningness; during weekdays, there were no
differences between the waking time of morning-type and evening-type students who
attended the morning shift. Second, with regard to sleep duration on weekdays,
students who attended the morning shift and were oriented to eveningness had the
shortest sleep duration. Furthermore, there were no differences between sleep
duration on weekdays in evening-type and morning-type students of the afternoon
shift. CONCLUSION: Adolescents who attend classes in the morning shift and are
oriented to eveningness are the most sleep deprived. Those who attend the
afternoon shift will have optimal sleep duration, regardless of their circadian
preference.
PMID- 26429756
TI - Transcranial magnetic stimulation for evaluation of motor cortical excitability
in restless legs syndrome/Willis-Ekbom disease.
AB - There is no consensus about mechanisms underlying restless legs syndrome (RLS),
also known as Willis-Ekbom disease (WED). Cortical excitability may be abnormal
in RLS. Transcranial magnetic stimulation (TMS) can provide insight about
cortical excitability. We reviewed studies about measures of excitability to TMS
in RLS. Original studies published between January 1999 and January 2015 were
searched in PubMed, Scopus, and Web of Science databases. Inclusion criteria were
as follows: original studies involving primary RLS in patients from both sexes
and ages between 18 and 85 years; TMS protocols clearly described; and they were
written in English, in peer-reviewed journals. Fifteen manuscripts were
identified. TMS protocols were heterogeneous across studies. Resting motor
threshold, active motor threshold, and amplitudes of motor-evoked potentials were
typically reported to be normal in RLS. A reduction in short-interval
intracortical inhibition (SICI) was the most consistent finding, whereas
conflicting results were described in regard to short-interval intracortical
facilitation and the contralateral silent period. Decreased SICI can be reversed
by treatment with dopaminergic agonists. Plasticity in the motor cortex and
sensorimotor integration may be disrupted. TMS may become a useful biomarker of
responsiveness to drug treatment in RLS. The field can benefit from increases in
homogeneity and sizes of samples, as well as from decrease in methodological
variability across studies.
PMID- 26429757
TI - Childhood abuse is associated with stress-related sleep disturbance and poor
sleep quality in pregnancy.
AB - OBJECTIVES: Childhood abuse is associated with increased risks of adult
psychiatric disorders and physical health conditions. Mounting evidence documents
associations of childhood abuse with sleep disturbances in adulthood. However, to
date, no study has evaluated associations of childhood abuse and sleep
disturbances among pregnant women. METHODS: This cross-sectional study included
634 pregnant Peruvian women. To collect information regarding socio-demographic
characteristics, history of childhood abuse, and complaints of sleep
disturbances, face-to-face interviews were conducted with women in early
pregnancy. Ford Insomnia Response to Stress Test (FIRST-S) and the Pittsburgh
Sleep Quality Index (PSQI-S), translated from English to Spanish, were used to
assess stress-related sleep disturbance and sleep quality, respectively. Logistic
regression was used to estimate adjusted odds ratios (aOR) and 95% confidence
intervals (95% CIs). RESULTS: Women who experienced any childhood abuse had a
1.65-fold increased odds of stress-related sleep disturbance (aOR = 1.65; 95% CI:
1.15-2.38) and 2.11-fold increased odds of poor sleep quality during early
pregnancy (aOR = 2.11; 95% CI: 1.35-3.30) as compared with women who reported no
abuse. Women who reported both physical and sexual abuse during childhood were
more than twice as likely to suffer from stress-related sleep disturbance (aOR =
2.26; 95% CI: 1.44-3.53) and poor sleep quality (aOR = 2.43; 95% CI: 1.45-4.09)
in comparison to women who reported no childhood abuse. CONCLUSIONS: A history of
childhood abuse is associated with increased odds of stress-related sleep
disturbance and poor sleep quality during pregnancy. These findings, if
replicated, should be used to inform the development of trauma-informed care for
such sleep disturbances induced by childhood trauma.
PMID- 26429758
TI - Sleep duration and growth outcomes across the first two years of life in the
GUSTO study.
AB - BACKGROUND AND AIM: Short sleep duration is thought to be a factor contributing
to increased body mass index (BMI) in both school-age children and adults. Our
aim was to determine whether sleep duration associates with growth outcomes
during the first two years of life. STUDY DESIGN: Participants included 899
children enrolled in the Growing Up in Singapore Towards healthy Outcomes (GUSTO)
birth cohort study. Anthropometric data (weight and body length) and parental
reports of sleep duration were collected at 3, 6, 9, 12, 18, and 24 months of
age. A mixed-model analysis was used to evaluate the longitudinal association of
BMI and body length with sleep duration. In subgroup analyses, effects of
ethnicity (Chinese, Indian, and Malay) and short sleep at three months of age
(<=12 h per day) were examined on subsequent growth measures. RESULTS: In the
overall cohort, sleep duration was significantly associated with body length
(beta = 0.028, 95% confidence interval [CI] 0.002-0.053, p = 0.033), but not BMI,
after adjustment for potential confounding factors. Only in Malay children,
shorter sleep was associated with a higher BMI (beta = -0.042, 95% CI -0.071 to
0.012, p = 0.005) and shorter body length (beta = 0.079, 95% CI 0.030-0.128, p =
0.002). In addition, shorter sleep was associated with a higher BMI and shorter
body length in children who slept <=12 h per day at three months of age.
CONCLUSION: The association between sleep duration and growth outcomes begins in
infancy. The small but significant relationship between sleep and growth
anthropometric measures in early life might be amplified in later childhood.
PMID- 26429759
TI - Correlated response of peripheral blood cytokines with selection for reduced
mycoplasma pneumonia of swine lesions in Landrace pigs.
AB - Mycoplasma pneumonia of swine (MPS) is responsible for significant economic
losses in the swine industry. We selected Landrace pigs for reduced MPS pulmonary
lesions over five generations, and measured concentrations of the following
cytokines: interleukin (IL)-10, IL-13, IL-17, tumor necrosis factor (TNF)-alpha
and interferon (IFN)-gamma to estimate their correlation with MPS lesions. Sheep
red blood cells (SRBC) were injected twice intramuscularly at 70 and 95 kg body
weight. Blood serum samples were collected after 1 week of secondary SRBC
inoculation and cytokine concentrations were analyzed by ELISA. Genetic
parameters and breeding values were estimated. The heritability estimates of IL
10, IL-13, IL-17, TNF-alpha and IFN-gamma were 0.20 +/- 0.06, 0.12 +/- 0.06, 0.27
+/- 0.07, 0.20 +/- 0.10 and 0.05 +/- 0.03, respectively. Genetic correlations of
IL-17 and TNF-alpha with pulmonary MPS lesions were high (-0.86 +/- 0.13 and 0.69
+/- 0.29, respectively) and those of IFN-gamma and IL-13 with MPS lesions were
moderately negative (-0.45). Through selection, the breeding values of IL-17 and
IFN-gamma increased substantially and those of TNF-alpha decreased. These results
suggest that innate and cellular immunity are more important for the suppression
of pulmonary lesions in MPS than humoral-mediated immunity, such as antibody
response.
PMID- 26429761
TI - Optical Coherence Tomography and Virtual-Histology Intravascular Ultrasound:
Strange Bedfellows? ... or Not?
PMID- 26429760
TI - Direct Comparison of Virtual-Histology Intravascular Ultrasound and Optical
Coherence Tomography Imaging for Identification of Thin-Cap Fibroatheroma.
AB - BACKGROUND: Although rupture of thin-cap fibroatheroma (TCFA) underlies most
myocardial infarctions, reliable TCFA identification remains challenging. Virtual
histology intravascular ultrasound (VH-IVUS) and optical coherence tomography
(OCT) can assess tissue composition and classify plaques. However, direct
comparisons between VH-IVUS and OCT are lacking and it remains unknown whether
combining these modalities improves TCFA identification. METHODS AND RESULTS: Two
hundred fifty-eight regions-of-interest were obtained from autopsied human
hearts, with plaque composition and classification assessed by histology and
compared with coregistered ex vivo VH-IVUS and OCT. Sixty-seven regions-of
interest were classified as fibroatheroma on histology, with 22 meeting criteria
for TCFA. On VH-IVUS, plaque (10.91+/-4.82 versus 8.42+/-4.57 mm(2); P=0.01) and
necrotic core areas (1.59+/-0.99 versus 1.03+/-0.85 mm(2); P=0.02) were increased
in TCFA versus other fibroatheroma. On OCT, although minimal fibrous cap
thickness was similar (71.8+/-44.1 MUm versus 72.6+/-32.4; P=0.30), the number of
continuous frames with fibrous cap thickness <=85 MUm was higher in TCFA (6.5
[1.75-11.0] versus 2.0 [0.0-7.0]; P=0.03). Maximum lipid arc on OCT was an
excellent discriminator of fibroatheroma (area under the curve, 0.92; 95%
confidence interval, 0.87-0.97) and TCFA (area under the curve, 0.86; 95%
confidence interval, 0.81-0.92), with lipid arc >=80 degrees the optimal cut-off
value. Using existing criteria, the sensitivity, specificity, and diagnostic
accuracy for TCFA identification was 63.6%, 78.1%, and 76.5% for VH-IVUS and
72.7%, 79.8%, and 79.0% for OCT. Combining VH-defined fibroatheroma and fibrous
cap thickness <=85 MUm over 3 continuous frames improved TCFA identification,
with diagnostic accuracy of 89.0%. CONCLUSIONS: Both VH-IVUS and OCT can reliably
identify TCFA, although OCT accuracy may be improved using lipid arc >=80 degrees
and fibrous cap thickness <=85 MUm over 3 continuous frames. Combined VH
IVUS/OCT imaging markedly improved TCFA identification.
PMID- 26429762
TI - Perovskites with the Framework-Forming Xenon.
AB - The Group 18 elements (noble gases) were the last ones in the periodic system to
have not been encountered in perovskite structures. We herein report the
synthesis of a new group of double perovskites KM(XeNaO6) (M = Ca, Sr, Ba)
containing framework-forming xenon. The structures of the new compounds, like
other double perovskites, are built up of the alternating sequence of corner
sharing (XeO6) and (NaO6) octahedra arranged in a three-dimensional rocksalt
order. The fact that xenon can be incorporated into the perovskite structure
provides new insights into the problem of Xe depletion in the atmosphere. Since
octahedrally coordinated Xe(VIII) and Si(IV) exhibit close values of ionic radii
(0.48 and 0.40 A, respectively), one could assume that Xe(VIII) can be
incorporated into hyperbaric frameworks such as MgSiO3 perovskite. The ability of
Xe to form stable inorganic frameworks can further extend the rich and still
enigmatic chemistry of this noble gas.
PMID- 26429763
TI - Alkenyl sex pheromone analogs in the hemolymph of an arctiid Eilema japonica and
several non-arctiid moths.
AB - The majority of moth species utilize compounds derived from de novo synthesized
fatty acids as their sex pheromones (type I). In contrast, species belonging to
two recently diverged moth families, Arctiidae and Geometridae, utilize alkenes
and their epoxides, which are derived from dietary essential fatty acids (EFAs),
as their sex pheromones (type II). In the latter species, EFAs are considered to
be converted into alkenes, often after chain elongation, in specialized cells
called oenocytes. These alkenes are transported through the hemolymph to the
pheromone gland, from which they are secreted with or without further
modifications. We confirmed that the appearance of EFA-derived alkenes in the
hemolymph was closely associated with the completion of pheromone gland formation
in an arctiid moth Eilema japonica. Analyses of the hemolymph of several moth
species utilizing type-I sex pheromones demonstrated the occurrence of (Z,Z,Z)
3,6,9-tricosatriene (T23), a typical type-II component, in the hemolymph of a
noctuid Mamestra brassicae and two crambids Ostrinia furnacalis and Ostrinia
scapulalis. Our results demonstrated that moths utilizing type-I pheromones have
the ability to synthesize type-II sex pheromones, and suggested that recently
diverged groups of moths may have secondarily exploited EFA-derived alkenes as
sex pheromones.
PMID- 26429764
TI - Myoepithelial carcinoma in the mediastinum involving the left atrium.
AB - We report a case of a 56-year-old male who presented with typical atrial flutter
and was diagnosed with a large mediastinal mass, posterior to the ascending
aorta, noted within the left atrium, compressing the superior vena cava and right
superior pulmonary vein, and measuring >9.0 cm at its greatest diameter.
Histopathological studies showed a myoepithelial carcinoma. The patient underwent
tumor debulking and radiation therapy. This is the first report of a mediastinal
myoepithelial carcinoma involving cardiac chambers.
PMID- 26429765
TI - Harvesting rice's dispensable genome.
AB - A rapid and cost-effective approach has been developed to harvest and map the
dispensable genome, that is, population-level natural sequence variation within a
species that is not present in static genome assemblies.
PMID- 26429766
TI - Diversity-Oriented Synthesis of Substituted Benzo[b]thiophenes and Their Hetero
Fused Analogues through Palladium-Catalyzed Oxidative C-H
Functionalization/Intramolecular Arylthiolation.
AB - An efficient, high yielding route to multisubstituted benzo[b]thiophenes has been
developed through palladium-catalyzed intramolecular oxidative C-H
functionalization-arylthiolation of enethiolate salts of alpha-aryl-beta
(het)aryl/alkyl-beta-mercaptoacrylonitriles/acrylates or acrylophenones. The
overall strategy involves a one-pot, two-step process in which enethiolate salts
[generated in situ through base-mediated condensation of substituted
arylacetonitriles, deoxybenzoins, or arylacetates with (het)aryl (or alkyl)
dithioates] are subjected to intramolecular C-H functionalization-arylthiolation
under the influence of a palladium acetate (or palladium chloride)/cupric acetate
catalytic system and tetrabutylammonium bromide as additive in N,N
dimethylformamide (DMF) as solvent. In a few cases, the yields of
benzo[b]thiophenes were better in a two-step process by employing the
corresponding enethiols as substrates. In a few examples, Pd(OAc)2 (or PdCl2)
catalyst in the presence of oxygen was found to be more efficient than cupric
acetate as reoxidant, furnishing benzothiophenes in improved yields by avoiding
formation of side products. The method is compatible with a diverse range of
substituents on the aryl ring as well as on the 2- and 3-positions of the
benzothiophene scaffold. The protocol could also be extended to the synthesis of
a raloxifene precursor and a tubulin polymerization inhibitor in good yields. The
versatility of this newly developed method was further demonstrated by
elaborating it for the synthesis of substituted thieno-fused heterocycles such as
thieno[2,3-b]thiophenes, thieno[2,3-b]indoles, thieno[3,2-c]pyrazole, and
thieno[2,3-b]pyridines in high yields. A probable mechanism involving
intramolecular electrophilic arylthiolation via either a Pd-S adduct or
palladacycle intermediate has been proposed on the basis of experimental studies.
PMID- 26429767
TI - (R)-[11C]Emopamil as a novel tracer for imaging enhanced P-glycoprotein function.
AB - INTRODUCTION: 2-Isopropyl-5-[methyl-(2-phenylethyl)amino]-2-phenylpentanenitrile
(emopamil; EMP) is a calcium channel blocker of the phenylalkylamine class, with
weak substrate properties for P-glycoprotein (P-gp). A weak substrate for P-gp
would be suitable for measuring enhanced P-gp function. This study was performed
to synthesise (R)- and (S)-[(11)C]EMP and characterise their properties as P-gp
tracers. METHODS: We synthesised (R)- and (S)-[(11)C]EMP and compared their
biodistribution, peripheral metabolism, and effects of the P-gp inhibitor
cyclosporine A (CsA, 50 mg/kg). We compared the brain pharmacokinetics of (R)
[(11)C]EMP and (R)-[(11)C]verapamil [(R)-[(11)C]VER] at baseline and CsA
pretreatment with small animal positron emission tomography (PET). RESULTS: (R)-
and (S)-[(11)C]EMP were synthesised from (R)- and (S)-noremopamil, respectively,
by methylation with [(11)C]methyl triflate in the presence of NaOH at room
temperature. (R)- and (S)-[(11)C]EMP yields were ~30%, with specific activity>74
GBq/MUmol and radiochemical purity>99%. (R)-[(11)C]EMP showed significantly
greater uptake in the mouse brain than (S)-[(11)C]EMP. Both showed homogeneous
non-stereoselective regional brain distributions. (R)- and (S)-[(11)C]EMP were
rapidly metabolised to hydrophilic metabolites. Unchanged plasma (S)-[(11)C]EMP
level was significantly lower than that of (R)-[(11)C]EMP 15 minutes post
injection, whilst>88% of radioactivity in the brain was intact at 15 minutes post
injection and was non-stereoselective. CsA pretreatment increased brain activity
~3-fold in mice, but was non-stereoselective. The baseline area-under-the-curve
(AUC) of brain radioactivity (0-60 minutes) of (R)-[(11)C]EMP was 2-fold higher
than that of (R)-[(11)C]VER, but their AUCs after CsA pretreatment were
comparable. CONCLUSIONS: (R)-[(11)C]EMP is a novel tracer for imaging P-gp
function with higher baseline uptake than (R)-[(11)C]VER.
PMID- 26429768
TI - Impact attenuation properties of new and used lacrosse helmets.
AB - The National Operating Committee on Standards for Athletic Equipment (NOCSAE) has
developed impact attenuation thresholds that protective helmets worn in sport
must meet to be commercially available in an attempt to prevent injury. It
remains unknown how normal helmet use in athletic activity alters the force
attenuation ability of lacrosse helmets. We tested 3 new and 3 randomly selected
used helmets from 2 popular lacrosse models (Cascade Pro7, Cascade CPXR). All
used helmets had been worn for 3 collegiate seasons prior to testing and had
never been refurbished. Helmets were drop-tested using 3 prescribed impact
velocities at 6 locations according to the NOCSAE lacrosse helmet standard, and
we compared the Gadd Severity Index (GSI) scores between new and used helmets
using a repeated measure ANOVA with location as the repeated variable and data
separated by impact velocity. All 12 helmets passed the NOCSAE GSI threshold for
all testing conditions; however 1 used helmet shell cracked resulting in a failed
test. We found a significant main effect for helmet age at the low (F5,50=2.98,
P=.02), medium (F5,50=3.71, P=.006), and high (F5,50=2.70, P=.03) velocities. We
suspect that helmet use can degrade materials under some conditions, but improve
performance in others due to changes in helmet composition from use. The clinical
implications of the differences in GSI scores noted remain unclear. Because one
helmet shell cracked resulting in a failed test, used helmets should be regularly
inspected for cracks or other signs of mechanical fatigue that may weaken helmet
integrity.
PMID- 26429769
TI - The envelope of passive motion allowed by the capsular ligaments of the hip.
AB - Laboratory data indicate the hip capsular ligaments prevent excessive range of
motion, may protect the joint against adverse edge loading and contribute to
synovial fluid replenishment at the cartilage surfaces of the joint. However,
their repair after joint preserving or arthroplasty surgery is not routine. In
order to restore their biomechanical function after hip surgery, the positions of
the hip at which the ligaments engage together with their tensions when they
engage is required. Nine cadaveric left hips without pathology were skeletonised
except for the hip joint capsule and mounted in a six-degrees-of-freedom testing
rig. A 5 N m torque was applied to all rotational degrees-of-freedom separately
to quantify the passive restraint envelope throughout the available range of
motion with the hip functionally loaded. The capsular ligaments allowed the hip
to internally/externally rotate with a large range of un-resisted rotation (up to
50+/-10 degrees ) in mid-flexion and mid-ab/adduction but this was reduced
towards the limits of flexion/extension and ab/adduction such that there was a
near-zero slack region in some positions (p<0.014). The slack region was not
symmetrical; the mid-slack point was found with internal rotation in extension
and external rotation in flexion (p<0.001). The torsional stiffness of the
capsular ligamentous restraint averaged 0.8+/-0.3 N m/ degrees and was greater
in positions where there were large slack regions. These data provide a target
for restoration of normal capsular ligament tensions after joint preserving hip
surgery. Ligament repair is technically demanding, particularly for arthroscopic
procedures, but failing to restore their function may increase the risk of
osteoarthritic degeneration.
PMID- 26429770
TI - Effect of propolis as a root canal irrigant on bond strength to dentin.
AB - PURPOSE: The purpose of this in vitro study was to evaluate the effect of
propolis on bond strength to dentin of a self-etch adhesive when used as a final
irrigant. METHODS: 126 human third molars were sectioned 3 mm below the occlusal
level and then randomly divided into 7 groups (n = 18). The exposed dentin
surfaces were treated with irrigation solutions as follows: Group 1: 5.25% NaOCl;
Group 2: 5.25% NaOCl followed by 17% EDTA; Group 3: 5.25% NaOCl followed by
Tubulicid Plus (Temrex, Freeport, NY, USA); Group 4: 5.25% NaOCl followed by
MTAD; Group 5: 5.25% NaOCl followed by 20% propolis; Group 6: 5.25% NaOCl
followed by 2% CHX; Group 7: distilled water (control). Irrigated specimens were
bonded using Clearfil SE Bond (Kuraray, Osaka, Japan) with Tygon (Saint-Gobain,
Saint-Gobain Performance Plastics, France), tubes for microshear bond strength
testing. Data was analyzed using a one-way ANOVA and Tukey test. RESULTS: Among
the tested groups, although the lowest bond strength values were detected in
Group 1 (11.25 +/- 1.97), a significant statistical difference was detected only
between this group and Group 4 (18.70 +/- 1.82) and Group 5 (16.75 +/- 3.70) (p =
0.0012). CONCLUSIONS: 20% propolis solution as a final irrigant was found to have
a favorable effect on the dentin bond strength of the tested self-etch adhesive
to coronal dentin when compared with other irrigation solutions.
PMID- 26429771
TI - Qualitative interviews with non-national tuberculosis patients in Cairo, Egypt:
understanding the financial and social cost of treatment adherence.
AB - Limited data are available about the challenges of non-national TB patients
undergoing long-term treatment courses in an urban setting. This study aimed to
understand the financial and social cost of adherence of non-national TB patients
in Cairo, Egypt as a means to inform the development of context-specific
interventions to support treatment adherence. In 2011, 22 in-depth interviews
were conducted with TB patients from Sudan, Ethiopia, Eritrea, Somalia and
Djibouti to obtain qualitative data. Analysis was based on thematic analysis that
aimed to identify recurrent themes and codes from the narratives. The study
identified a number of factors that influence TB treatment adherence. Uncertain
financial status due to limited or no employment was frequently discussed in
interviews, which resulted in fear of not being able to support family, loss of
pride, dependence on family and friends, fear of losing housing, food insecurity
and limited food options. Respondents also feared infecting other household
members and longed for opportunities to discuss their illness and treatment
experiences with other individuals but their social networks were often limited.
TB-related stigma was driven by shame and blame of infection. Respondents also
believed stigma was based on their foreign origin. Stigma manifested in
distancing and exclusion in various ways, resulting in isolation, psychological
distress and reluctance to disclose TB status to others. Poverty-related factors
and social context with a special focus on stigma should be considered when
developing strategies for supporting long-term treatment courses for non-national
patients in Cairo and other similar urban settings.
PMID- 26429772
TI - Youth motivation as a predictor of treatment outcomes in a community mental
health system.
AB - OBJECTIVE: The purpose of this study was to examine the relationship between
youth motivation and psychotherapy outcomes in routine community mental health
settings. METHOD: One hundred fifty youth, ages 12-17, from three community
mental health clinics completed the Youth Outcome Questionnaire and Treatment
Support Measure at frequent intervals over the course of treatment. RESULTS:
Increases in motivation followed a curvilinear trajectory. On average, youth
motivation significantly increased over the course of therapy according to both
self- and parent reports (p < .001). The slope for youth motivation over the
course of therapy was negatively associated with the slope for mental health
symptoms (p < .001). Initial youth motivation did not predict overall change or
the rate of change in symptoms. However, there was significant individual
variability in patterns of youth motivation. CONCLUSIONS: Our findings
demonstrate that youth show increases in motivation over the course of therapy
with most gains occurring in the first few sessions. Because increases in
motivation over the course of therapy were related to decreases in mental health
symptoms, further research is needed to examine how treatment interventions or
other factors such as parent motivation may moderate this relationship.
Additional research examining the likely complex relationship between initial
youth motivation and treatment outcomes in community mental health settings is
needed.
PMID- 26429773
TI - Drug-induced secretory diarrhea: A role for CFTR.
AB - Many medications induce diarrhea as a side effect, which can be a major obstacle
to therapeutic efficacy and also a life-threatening condition. Secretory diarrhea
can be caused by excessive fluid secretion in the intestine under pathological
conditions. The cAMP/cGMP-regulated cystic fibrosis transmembrane conductance
regulator (CFTR) is the primary chloride channel at the apical membrane of
intestinal epithelial cells and plays a major role in intestinal fluid secretion
and homeostasis. CFTR forms macromolecular complexes at discreet microdomains at
the plasma membrane, and its chloride channel function is regulated
spatiotemporally through protein-protein interactions and cAMP/cGMP-mediated
signaling. Drugs that perturb CFTR-containing macromolecular complexes in the
intestinal epithelium and upregulate intracellular cAMP and/or cGMP levels can
hyperactivate the CFTR channel, causing excessive fluid secretion and secretory
diarrhea. Inhibition of CFTR chloride-channel activity may represent a novel
approach to the management of drug-induced secretory diarrhea.
PMID- 26429774
TI - A characteristic of polymorphic membrane protein F of Chlamydia trachomatis
isolated from male urogenital tracts in Japan.
AB - Although sexually transmitted disease due to Chlamydia trachomatis occurs
similarly in both men and women, the female urogenital tract differs from that of
males anatomically and physiologically, possibly leading to specific
polymorphisms of the bacterial surface molecules. In the present study, we
therefore characterized polymorphic features in a high-definition phylogenetic
marker, polymorphic outer membrane protein (Pmp) F of C. trachomatis strains
isolated from male urogenital tracts in Japan (Category: Japan-males, n = 12),
when compared with those isolated from female cervical ducts in Japan (Category:
Japan-females, n = 11), female cervical ducts in the other country (Category: Ref
females, n = 12) or homosexual male rectums in the other country (Category: Ref
males, n = 7), by general bioinformatics analysis tool with MAFFT software. As a
result, phylogenetic reconstruction of the PmpF amino acid sequences showing
three distinct clusters revealed that the Japan-males were limited into cluster 1
and 2, although there were only four clusters even though including an outgroup.
Meanwhile, the phylogenetic distance values of PmpF passenger domain without
hinge region, but not its full-length sequence, showed that the Japan-males were
more stable and displayed less diversity when compared with the other categories,
supported by the sequence conservation features. Thus, PmpF passenger domain is a
useful phylogenetic maker, and the phylogenic features indicate that C.
trachomatis strains isolated from male urogenital tracts in Japan may be unique,
suggesting an adaptation depending on selective pressure, such as the presence or
absence of microbial flora, furthermore possibly connecting to sexual
differentiation.
PMID- 26429775
TI - Stenting in paediatric and adult congenital heart diseases: A French multicentre
study in the current era.
AB - BACKGROUND: Many stents are used "off-label" during the management of congenital
heart diseases (CHD). AIMS: To describe indications for, results of, and adverse
events associated with stenting in CHD in current practice. METHODS:
Participation in this study was proposed to all catheterization laboratories that
specialize in CHD in France (M3C network). All paediatric and adult CHD cases
with stent implantation in 2013 were included retrospectively. RESULTS: Overall,
207 stents were implanted in 151 patients across 11 centres. Median age was 13.7
years (range, 5 days to 70.1 years). Main procedure indications were branch
pulmonary artery angioplasty (n=46, 29.1%), aortic (re)coarctation stenting
(n=43, 27.2%), percutaneous pulmonary valve implantation (n=32, 20.2%) and ductus
arteriosus stenting (n=14, 8.9%). The main stents implanted were the CP StentTM
(n=61, 29.5%), the MaxTM LD stent (n=43, 20.8%), the Valeo((r)) stent (n=28,
13.5%) and valved stents (n=30, 14.5%). Procedures were considered successful in
96.8% of cases (95% confidence interval [CI] 92.8-99.0%). Adverse events were
observed in 23 procedures (14.7%, 95% CI 9.5-21.0%). Ductus arteriosus stenting
(odds ratio 12.4, 95% CI 2.0-77.5; P<0.01) and pulmonary revalvulation (odds
ratio 5.9, 95% CI 1.1-32.3; P=0.04) were risk markers for stent-related adverse
events. CONCLUSIONS: Stents are used in various CHD catheterization procedures,
from infancy to adult age. The adverse events rate is significant and is related
to the type of procedure.
PMID- 26429776
TI - Editorial: Identification of in vivo markers for human polarized macrophages: a
need that's finally met.
PMID- 26429777
TI - Editorial: "Crowning" eosinophils in adipose tissue: does location matter?
PMID- 26429779
TI - Standardization of FT4 and harmonization of TSH measurements: a request for input
from endocrinologists and other physicians.
PMID- 26429778
TI - Adenovirus infection in children with acute lower respiratory tract infections in
Beijing, China, 2007 to 2012.
AB - BACKGROUND: Human adenoviruses (HAdV) play a significant role in pediatric
respiratory tract infections. To date, over 60 types of HAdV have been
identified. Here, HAdV types are characterized in children in the Beijing area
with acute lower respiratory tract infections (ALRTIs) and the clinical features
and laboratory findings of hospitalized HAdV-infected cases are described.
METHODS: Respiratory specimens were collected from pediatric patients with ALRTIs
in the emergency department or from those admitted to Beijing Children's Hospital
between March 2007 and December 2012. Infections with common respiratory viruses
were determined by PCR or RT-PCR. HAdV positive samples were further typed by PCR
and sequencing. RESULTS: Among 3356 patients with ALRTIs, 194 (5.8 %) were found
to have HAdV infection. HAdV infection was primarily confined to children (88.35
%) less than 5 years of age. A total of 11 different types of HAdV were detected
throughout the study period, with HAdV-B7 (49.0 %) and HAdV-B3 (26.3 %) as the
most prevalent types, followed by HAdV-C2 (7.7 %) and HAdVC1 (4.6 %). Newly
emerging and re-emergent types or variants, HAdV-B55 (n = 5), HAdV-C57 (n = 3),
and HAdV-B14p1 (n = 1), were identified. Results also included the reported first
case of co-infection with HAdV-C2 and HAdV-C57. Clinical entities of patients
with single HAdV infection (n = 49) were similar to those with mixed
HAdV/respiratory syncytial virus (RSV) infections (n = 41). Patients with HAdV-B7
infection had longer duration of fever and higher serum levels of muscle enzymes
than HAdV-B3-infected patients. CONCLUSIONS: During the study period, HAdV-B7 and
HAdV-B3 were the predominant types identified in pediatric ALRTIs. HAdV-B7
infection tends to have more severe clinical consequences. The presence of newly
emerging types or variants and co-infection with different types of HAdV
highlights the need for constant and close surveillance of HAdV infection.
PMID- 26429782
TI - Primary iliopsoas abscess in a patient with diabetic foot.
PMID- 26429780
TI - The association of obesity with hearing thresholds in women aged 18-40 years.
AB - An elevation in hearing thresholds and decrease in hearing sensitivity in adults,
particularly due to aging, are quite common. Recent studies have shown that,
apart from aging, various other factors also play a role in auditory changes.
Studies on the association of hearing loss (HL) with obesity are limited in
advanced age cases and present contradictions. In this study, the association
between obesity and hearing thresholds in women aged 18-40 years has been
assessed. Forty women diagnosed with obesity (mean age, 31.8 years) and 40
healthy non-obese female controls (mean age, 30.5 years) were included in this
prospective study. Each subject was tested with low (250, 500, 1000 and 2000 Hz)
and high (4000, 6000 and 8000 Hz) frequency audiometry. In the case and control
groups, the average hearing thresholds at low frequencies were 16.03 +/- 4.72 and
16.15 +/- 2.72 (p = 0.885) for the right ear, respectively, and 16.15 +/- 5.92
and 14.71 +/- 3.18 (p = 0.180) for the left ear, respectively. The average
hearing threshold levels at high frequencies were 20.70 +/- 10.23 and 15.33 +/-
3.87 (p = 0.003), respectively, for the right ear, and 22.91 +/- 15.54 and 15.87
+/- 4.35 (p = 0.007), respectively, for the left ear with statistical
significance. This is the first report on the association of obesity with hearing
threshold in women aged 18-40 years. We have demonstrated that obesity may affect
hearing function, particularly that related to high frequencies. Hearing loss can
be prevented by avoidance or control of obesity and its risk factors. Moreover,
an auditory screening of obese cases at an early stage may provide early
diagnosis of HL and may also contribute to their awareness in the fight against
obesity.
PMID- 26429781
TI - Increased osteoporosis risk in dermatomyositis or polymyositis independent of the
treatments: a population-based cohort study with propensity score.
AB - We investigated the relationship between dermatomyositis/polymyositis (DM/PM) and
the risk of subsequent osteoporosis development. A population-based retrospective
cohort analysis was conducted using the National Health Insurance Research
Database and the Catastrophic Illness Patients Database of Taiwan. We included
1179 patients and 4716 patients from 1999 to 2008 as the DM/PM cohort and the
comparison cohort, respectively, and calculated the incidence rates of newly
diagnosed osteoporosis. We used Cox proportional hazards models stratified on
matched pair to assess the effect of DM/PM. The Kaplan-Meier method was applied
to estimate the cumulative osteoporosis incidence curves. Patients with DM/PM
were 2.99 times more likely to experience osteoporosis than those without DM/PM.
The risk for osteoporosis in DM/PM patients was higher than comparisons in
different propensity score quartiles. DM/PM cohort, no matter treated with or
without corticosteroids and immunosuppressant, had a higher risk than the
comparison cohort. The incidence of osteoporosis in Taiwan is associated with a
priori DM/PM history. This risk was independent of the corticosteroids and
immunosuppressant treatment.
PMID- 26429783
TI - Diabetes as a model for the disparate public response to acute versus chronic
diseases.
AB - The public health outcry toward infectious entities appears to dwarf chronic
diseases such as diabetes. This disparity is particularly astonishing given the
considerable prevalence of diabetes and prediabetes. Diseases associated with
short-term morbidity and mortality therefore seem to garner attention and demand
an immediate public health response, whereas chronic illnesses, which can be
considerably more devastating in the longer term, receive relatively less
notoriety. It should not, however, be misconstrued that one disease entity is
more important than the other--it is critical that both acute and chronic
entities are given balanced attention in the public health, governmental, and
scientific realms. The current perspective reflects on the disparate public
health purviews toward acute and chronic illnesses, describes why prevention is
so difficult and challenging, and addresses what can be done to reverse this
trend. If there is any hope of conquering the spiraling prediabetes and diabetes
epidemics, the medical community must grapple with the complex issues herein
raised.
PMID- 26429784
TI - Common Non-classically Secreted Bacterial Proteins with Experimental Evidence.
AB - The non-classically secreted proteins are the proteins that are located in the
extracellular milieu despite the absence of known signal peptides or other
targeting peptides. Numerous experimental studies have discovered many non
classically secreted proteins, but there are many inconsistencies in these
reports even on a specific organism. In order to reduce the impact of artefactual
contamination of protein samples and cell lysis, this review listed 45 common non
classically secreted proteins. The list of non-classically secreted proteins was
complied from studies carried out by different groups in various bacterial
species. The complied list can provide a reliable experimental material for
further research on non-classical protein secretion. It is noticeable that some
of these proteins are hyper-secreted when expressed in specific species or under
some induction conditions. So we also discussed the possibilities of using the
non-classical secretion pathway for the production of recombinant proteins in the
review.
PMID- 26429785
TI - Clinical application of a surgical navigation system based on virtual laparoscopy
in laparoscopic gastrectomy for gastric cancer.
AB - PURPOSE: Knowledge of the specific anatomical information of a patient is
important when planning and undertaking laparoscopic surgery due to the
restricted field of view and lack of tactile feedback compared to open surgery.
To assist this type of surgery, we have developed a surgical navigation system
that presents the patient's anatomical information synchronized with the
laparoscope position. This paper presents the surgical navigation system and its
clinical application to laparoscopic gastrectomy for gastric cancer. METHODS: The
proposed surgical navigation system generates virtual laparoscopic views
corresponding to the laparoscope position recorded with a three-dimensional (3D)
positional tracker. The virtual laparoscopic views are generated from
preoperative CT images. A point-based registration aligns coordinate systems
between the patient's anatomy and image coordinates. The proposed navigation
system is able to display the virtual laparoscopic views using the registration
result during surgery. RESULTS: We performed surgical navigation during
laparoscopic gastrectomy in 23 cases. The navigation system was able to present
the virtual laparoscopic views in synchronization with the laparoscopic position.
The fiducial registration error was calculated in all 23 cases, and the average
was 14.0 mm (range 6.1-29.8). CONCLUSION: The proposed surgical navigation system
can provide CT-derived patient anatomy aligned to the laparoscopic view in real
time during surgery. This system enables accurate identification of vascular
anatomy as a guide to vessel clamping prior to total or partial gastrectomy.
PMID- 26429786
TI - Automatic 3D modelling of human diaphragm from lung MDCT images.
AB - PURPOSE: The thoracic diaphragm separates the thorax and abdomen cavity and also
performs an important function in respiration. An automatic algorithm to model
the human full diaphragm from multi-detector computed tomography (MDCT) images
has been developed and tested. METHOD: The modelling algorithm comprises these
steps: (i) diaphragm top boundary estimation (ii) diaphragm side boundary
estimation and (iii) full diaphragm modelling in 3D. Diaphragm top boundary is
estimated based on lungs' diaphragmatic surfaces with three different methods
including: linear interpolation and fitting fourth and fifth degree polynomial
surfaces. Diaphragm side boundary is assumed as the inner surfaces of the lower
ribs, spinal column and costal cartilages, estimated via interpolation. As the
last step, the full diaphragm is modelled by employing 3D active contours that
are initiated from a predefined mesh and expand towards the estimated boundaries
of the diaphragm. The proposed algorithm was tested on MDCT datasets from 15
patients, and the result were compared to reference masks provided by an
experienced radiologist. RESULTS: Based on quantitative evaluations, the accuracy
of the algorithm highly depends on the diaphragm top surface estimation, e.g.,
the proposed algorithm failed on two datasets, both with enlarged pericardial fat
pad that cuts off the left lung from the diaphragm. The proposed algorithm was
tested on the remaining 13 datasets in which lungs' lower surfaces have normal
contact with the diaphragm. To perform quantitative evaluations, four slices per
dataset including an axial, mid-coronal and one-fourth of the sagittal planes
from left and right, were compared to the ground truth. Hausdorff distance and
mean distance to the closest point were measured to be 11.61 and 3.46 mm
respectively, when the diaphragm top surface is modelled by a fourth degree
polynomial surface. CONCLUSION: Human full diaphragm can be automatically
modelled with 3D active contours bounded by the lower surfaces of the lungs and
inner surfaces of the lower ribs, spinal column and costal cartilages.
PMID- 26429787
TI - Vision-based real-time position control of a semi-automated system for robot
assisted joint fracture surgery.
AB - PURPOSE: Joint fracture surgery quality can be improved by robotic system with
high-accuracy and high-repeatability fracture fragment manipulation. A new real
time vision-based system for fragment manipulation during robot-assisted fracture
surgery was developed and tested. METHODS: The control strategy was accomplished
by merging fast open-loop control with vision-based control. This two-phase
process is designed to eliminate the open-loop positioning errors by closing the
control loop using visual feedback provided by an optical tracking system.
Evaluation of the control system accuracy was performed using robot positioning
trials, and fracture reduction accuracy was tested in trials on ex vivo porcine
model. RESULTS: The system resulted in high fracture reduction reliability with a
reduction accuracy of 0.09 mm (translations) and of [Formula: see text]
(rotations), maximum observed errors in the order of 0.12 mm (translations) and
of [Formula: see text] (rotations), and a reduction repeatability of 0.02 mm and
[Formula: see text]. CONCLUSIONS: The proposed vision-based system was shown to
be effective and suitable for real joint fracture surgical procedures,
contributing a potential improvement of their quality.
PMID- 26429788
TI - Association of Intraluminal Thrombus, Hemodynamic Forces, and Abdominal Aortic
Aneurysm Expansion Using Longitudinal CT Images.
AB - While hemodynamic forces and intraluminal thrombus (ILT) are believed to play
important roles on abdominal aortic aneurysm (AAA), it has been suggested that
hemodynamic forces and ILT also interact with each other, making it a complex
problem. There is, however, a pressing need to understand relationships among
three factors: hemodynamics, ILT accumulation, and AAA expansion for AAA
prognosis. Hence this study used longitudinal computer tomography scans from 14
patients and analyzed the relationship between them. Hemodynamic forces,
represented by wall shear stress (WSS), were obtained from computational fluid
dynamics; ILT accumulation was described by ILT thickness distribution changes
between consecutives scans, and ILT accumulation and AAA expansion rates were
estimated from changes in ILT and AAA volume. Results showed that, while low WSS
was observed at regions where ILT accumulated, the rate at which ILT accumulated
occurred at the same rate as the aneurysm expansion. Comparison between AAAs with
and without thrombus showed that aneurysm with ILT recorded lower values of WSS
and higher values of AAA expansion than those without thrombus. Findings suggest
that low WSS may promote ILT accumulation and submit the idea that by increasing
WSS levels ILT accumulation may be prevented.
PMID- 26429789
TI - Physical and Biological Modification of Polycaprolactone Electrospun Nanofiber by
Panax Ginseng Extract for Bone Tissue Engineering Application.
AB - Medicinal plants as a therapeutic agent with osteogenic properties can enhance
fracture-healing process. In this study, the osteo-inductive potential of Asian
Panax Ginseng root extract within electrospun polycaprolactone (PCL) based
nanofibers has been investigated. Scanning electron microscopy images revealed
that all nanofibers were highly porous and beadles with average diameter ranging
from 250 to 650 nm. The incorporation of ginseng extract improved the physical
characteristics (i.e., hydrophilicity) of PCL nanofibers, as well as the
mechanical properties. Although ginseng extract increased the degradation rate of
pure PCL nanofibers, the porous structure and morphology of fibers did not change
significantly after 42 days. It was found that nanofibrous scaffolds containing
ginseng extract had higher proliferation (up to ~1.5 fold) compared to the
pristine PCL. The qRT-PCR analysis demonstrated the addition of ginseng extract
into PCL nanofibers induced significant expression of osteogenic genes
(Osteocalcin, Runx-2 and Col-1) in MSCs in a concentration dependent manner.
Moreover, higher calcium content, alkaline phosphatase activity and higher
mineralization of MSCs were observed compared to the pristine PCL fibers. Our
results indicated the promising potential of ginseng extract as an additive to
enhance osteo-inductivity, mechanical and physical properties of PCL nanofibers
for bone tissue engineering application.
PMID- 26429790
TI - Surgical management of secondary hyperparathyroidism in chronic kidney disease--a
consensus report of the European Society of Endocrine Surgeons.
AB - BACKGROUND: Despite advances in the medical management of secondary
hyperparathyroidism due to chronic renal failure and dialysis (renal
hyperparathyroidism), parathyroid surgery remains an important treatment option
in the spectrum of the disease. Patients with severe and complicated renal
hyperparathyroidism (HPT), refractory or intolerant to medical therapy and
patients with specific requirements in prospect of or excluded from renal
transplantation may require parathyroidectomy for renal hyperparathyroidism.
METHODS: Present standard and actual controversial issues regarding surgical
treatment of patients with hyperparathyroidism due to chronic renal failure were
identified, and pertinent literature was searched and reviewed. Whenever
applicable, evaluation of the level of evidence concerning diagnosis and
management of renal hyperparathyroidism according to standard criteria and
recommendation grading were employed. Results were discussed at the 6th Workshop
of the European Society of Endocrine Surgeons entitled Hyperparathyroidism due to
multiple gland disease: An evidence-based perspective. RESULTS: Presently,
literature reveals scant data, especially, no prospective randomized studies to
provide sufficient levels of evidence to substantiate recommendations for surgery
in renal hyperparathyroidism. Appropriate surgical management of renal
hyperparathyroidism involves standard bilateral exploration with bilateral
cervical thymectomy and a spectrum of four standardized types of parathyroid
resection that reveal comparable outcome results with regard to levels of
evidence and recommendation. Specific patient requirements may favour one over
the other procedure according to individualized demands. CONCLUSIONS: Surgery for
patients with renal hyperparathyroidism in the era of calcimimetics continues to
play an important role in selected patients and achieves efficient control of
hyperparathyroidism. The overall success rate and long-term control of renal
hyperparathyroidism and optimal handling of postoperative metabolic effects also
depend on the timely indication, individually suitable type of parathyroid
resection and specialized endocrine surgery.
PMID- 26429791
TI - Emotional traits predict individual differences in amphetamine-induced positive
mood in healthy volunteers.
AB - BACKGROUND: Previous research on emotional correlates of individual differences
in subjective responses to D-amphetamine has focused on relatively broad
personality traits. Yet, emotional functioning is best characterized by several
narrow subcomponents, each of which may contribute uniquely to amphetamine
response. Here, we examine several specific subdomains of emotional functioning
in relation to acute amphetamine response. METHOD: At a baseline session, healthy
stimulant-naive volunteers (N = 97) completed measures of several subdomains of
baseline trait emotional functioning and then completed two counterbalanced
experimental sessions during which they received a single oral dose of 20 mg D
amphetamine or placebo. Acute subjective drug response measures were completed at
repeated intervals before and after drug administration. Data from subjective
measures that were significantly modulated by amphetamine were reduced using
principal component analysis (amphetamine or placebo) into three higher-order
factors of "positive mood," "arousal," and "drug high." Amphetamine did not
significantly alter any "negative" subjective states. Separate multiple
regression analyses were conducted regressing these three drug factors on
baseline trait emotional functioning scales. RESULTS: The combined set of trait
emotional functioning indicators accounted for approximately 22 % of the variance
in acute amphetamine-induced positive mood changes. Greater anticipatory pleasure
and greater anxious distress each uniquely predicted greater amphetamine-induced
positive mood. Trait emotional functioning did not significantly predict
amphetamine-induced changes in arousal or drug high. DISCUSSION: Emotional traits
appear to moderate drug-induced positive mood but not other dimensions of
amphetamine effects. Different facets of emotional functioning may differentially
modulate amphetamine's subjective effect profile.
PMID- 26429792
TI - Contact in the Classroom: Developing a Program Model for Youth Mental Health
Contact-Based Anti-stigma Education.
AB - This study evaluated eighteen Canadian anti-stigma programs targeting high-school
students. The purpose was to identify critical domains and develop a program
model of contact-based interventions. Three steps were implemented. The first
step involved collecting program information through twenty in-depth interviews
with stakeholders and field observations of seven programs. The second step
involved constructing critical ingredients into domains for conceptual clarity
and component modeling. The third step involved validating the program model by
stakeholders review and initial fidelity testing with program outcomes. A program
model with an overarching theme "engaging contact reduces stigma" and three
underlying constructs (speakers, message, and interaction) were developed. Within
each construct three specific domains were identified to explain the concepts.
Connection, engagement, and empowerment are critical domains of anti-stigma
programs for the youth population. Findings from this study have built on the
scientific knowledge about the change theory underpinning youth contact-based
intervention.
PMID- 26429793
TI - Cyclic mechanical strain of myocytes modifies CapZbeta1 post translationally via
PKCepsilon.
AB - The heart is exquisitely sensitive to mechanical stimuli and adapts to increased
demands for work by enlarging the cardiomyocytes. In order to determine links
between mechano-transduction mechanisms and hypertrophy, neonatal rat ventricular
myocytes (NRVM) were subjected to physiologic strain for analysis of the dynamics
of the actin capping protein, CapZ, and its post-translational modifications
(PTM). CapZ binding rates were assessed after strain by fluorescence recovery
after photobleaching (FRAP) of green fluorescent protein (GFP) expressed by a GFP
CapZbeta1 adenovirus. To assess the role of the protein kinase C epsilon isoform
(PKCepsilon), rest or cyclic strain were combined with specific PKCepsilon
activation by constitutively active PKCepsilon, or by inhibition with dominant
negative PKCepsilon (dnPKCepsilon) expression. Significant increases of CapZ FRAP
kinetics with strain were blunted by dnPKCepsilon, suggesting that PKCepsilon is
involved in mechano-transduction signaling. Similar combinations of strain and
PKC regulation in NRVMs were studied by PTM profiles of CapZbeta1 using
quantitative two-dimensional gel electrophoresis. The significantly increased
charge on CapZ seen with mechanical strain was reversed by the addition of
dnPKCepsilon. Potential clinical relevance was confirmed in vivo by PTMs of CapZ
in the failing heart of one-year old transgenic mice over-expressing PKCepsilon.
Furthermore, with strain there was significant PKCepsilon translocation to the Z
disc and co-localization with CapZbeta1 or alpha-actinin, which was quantified on
confocal images. A hypothetical model is presented proposing that one destination
of the mechanotransduction signaling pathways might be for PTMs of CapZ thereby
regulating actin capping and filament assembly.
PMID- 26429795
TI - Cost-analysis of teledentistry in residential aged care facilities.
AB - INTRODUCTION: The purpose of this research was to conduct a cost-analysis, from a
public healthcare perspective, comparing the cost and benefits of face-to-face
patient examination assessments conducted by a dentist at a residential aged care
facility (RACF) situated in rural areas of the Australian state of Victoria, with
two teledentistry approaches utilizing virtual oral examination. METHODS: The
costs associated with implementing and operating the teledentistry approach were
identified and measured using 2014 prices in Australian dollars. Costs were
measured as direct intervention costs and programme costs. A population of 100
RACF residents was used as a basis to estimate the cost of oral examination and
treatment plan development for the traditional face-to-face model vs. two
teledentistry models: an asynchronous review and treatment plan preparation; and
real-time communication with a remotely located oral health professional.
RESULTS: It was estimated that if 100 residents received an asynchronous oral
health assessment and treatment plan, the net cost from a healthcare perspective
would be AU$32.35 (AU$27.19-AU$38.49) per resident. The total cost of the
conventional face-to-face examinations by a dentist would be AU$36.59 ($30.67
AU$42.98) per resident using realistic assumptions. Meanwhile, the total cost of
real-time remote oral examination would be AU$41.28 (AU$34.30-AU$48.87) per
resident. DISCUSSION: Teledental asynchronous patient assessments were the lowest
cost service model. Access to oral health professionals is generally low in
RACFs; however, the real-time consultation could potentially achieve better
outcomes due to two-way communication between the nurse and a remote oral health
professional via health promotion/disease prevention delivered in conjunction
with the oral examination.
PMID- 26429794
TI - Assessing quality of life in severe obesity: development and psychometric
properties of the ORWELL-R.
AB - PURPOSE: Several health-related quality-of-life (HRQoL) dimensions are affected
by obesity. Our goal was to characterize the psychometric properties of the
ORWELL-R, a new obesity-related quality-of-life instrument for assessing the
"individual experience of overweightness". METHODS: This psychometric assessment
included two different samples: one multicenter clinical sample, used for
assessing internal consistency, construct validity and temporal reliability; and
a community sample (collected through a cross-sectional mailing survey design),
used for additional construct validity assessment and model fit confirmation.
RESULTS: Overall, 946 persons participated (188 from the clinical sample; 758
from community sample). An alpha coefficient of 0.925 (clinical sample) and 0.934
(community sample) was found. Three subscales were identified (53.2 % of
variance): Body environment experience (alpha = 0.875), Illness perception and
distress (alpha = 0.864), Physical symptoms (alpha = 0.674). Adequate test-retest
reliability has been confirmed (ICC: 0.78 for the overall score). ORWELL-R scores
were worse in the clinical sample. Worst HRQoL, as measured by higher ORWELL-R
scores, was associated with BMI increases. ORWELL-R scores were associated with
IWQOL-Lite and lower scores in happiness. CONCLUSIONS: ORWELL-R shows good
internal consistency and adequate test-retest reliability. Good construct
validity was also observed (for convergent and discriminant validity) and
confirmed through confirmatory factor analysis (in both clinical and community
samples). Presented data sustain ORWELL-R as a reliable and useful instrument to
assess obesity-related QoL, in both research and clinical contexts.
PMID- 26429796
TI - Reality versus regulation.
PMID- 26429797
TI - Commentary on the OPTIDUAL trial results: how to optimise prolonged dual
antiplatelet treatment and independent randomised clinical trials.
PMID- 26429798
TI - Nox4 NADPH oxidase: emerging from the veil of darkness.
PMID- 26429800
TI - Co(2+)@Mesoporous Silica Monoliths: Tailor-Made Nanoreactors for Confined Soft
Chemistry.
AB - Mesoporous silica monoliths with various ordered nanostructures containing
transition metal M(2+) cations in variable amounts were elaborated and studied. A
phase diagram depicting the different phases as a function of the M(2+)
salt/tetramethyl orthosilicate (TMOS) and surfactant P123/TMOS ratios was
established. Thermal treatment resulted in mesoporous monoliths containing
isolated, accessible M(2+) species or condensed metal oxides, hydroxides, and
salts, depending on the strength of the interactions between the metal species
and the ethylene oxide units of P123. The ordered mesoporosity of the monoliths
containing accessible M(2+) ions was used as a nanoreactor for the elaboration of
various transition metal compounds (Prussian blue analogues, Hofmann compounds,
metal-organic frameworks), and this opens the way to the elaboration of a large
range of nanoparticles of multifunctional materials.
PMID- 26429799
TI - Catheter-based interventions for acute ischaemic stroke.
AB - Catheter-based interventions for acute ischaemic stroke currently include clot
removal (usually from the medial cerebral artery) with modern stent-retrievers
and in one of five patients (who have simultaneous or stand-alone internal
carotid occlusion) also extracranial carotid intervention. Several recently
published randomized trials clearly demonstrated superiority of catheter-based
interventions (with or without bridging thrombolysis) over best medical therapy
alone. The healthcare systems should adopt the new strategies for acute stroke
treatment (including fast track to interventional lab) to offer the benefits to
all suitable acute stroke patients.
PMID- 26429801
TI - Fatty acid hydration activity of a recombinant Escherichia coli-based biocatalyst
is improved through targeting the oleate hydratase into the periplasm.
AB - Whole-cell biotransformation of fatty acids can be influenced by the activities
of catalytic enzymes and by the efficiency of substrate transport into host
cells. Here, we improved fatty acid hydration activity of the recombinant
Escherichia coli expressing an oleate hydratase of Stenotrophomonas maltophilia
by targeting the catalytic enzyme into the periplasm instead of the cytoplasm.
Recombinant E. coli producing OhyA in the periplasm under guidance of the PelB
signal sequence (E. coli OhyA_PP) exhibited significantly greater hydration
activity with oleic acid and linoleic acid compared to a recombinant E. coli
producing OhyA in the cytoplasm (E. coli OhyA_CS). For example, the oleate double
bond hydration rate of E. coli OhyA_PP was >400 MUmol/g dry cells/min (400 U/g
dry cells), which is >10-fold higher than that of E. coli OhyA_CS. As the
specific activities of the enzymes targeted into the cytoplasm and periplasm were
comparable, we assumed that targeting OhyA into the periplasm could accelerate
fatty acid transport to the catalytic enzymes by skipping the major mass
transport barrier of the cytoplasmic membrane. Our results will contribute to the
development of whole-cell biocatalysts for fatty acid biotransformation.
PMID- 26429803
TI - Identification of a new HLA-A*24 allele, A*24:313.
AB - The new allele, A*24:313, showed one nucleotide difference with A*24:02:01
(595G>A).
PMID- 26429804
TI - The role of inflammatory cells in tendinopathy: is the picture getting any
clearer?
PMID- 26429802
TI - Matrigel Mattress: A Method for the Generation of Single Contracting Human
Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
AB - RATIONALE: The lack of measurable single-cell contractility of human-induced
pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) currently limits the
utility of hiPSC-CMs for evaluating contractile performance for both basic
research and drug discovery. OBJECTIVE: To develop a culture method that rapidly
generates contracting single hiPSC-CMs and allows quantification of cell
shortening with standard equipment used for studying adult CMs. METHODS AND
RESULTS: Single hiPSC-CMs were cultured for 5 to 7 days on a 0.4- to 0.8-mm thick
mattress of undiluted Matrigel (mattress hiPSC-CMs) and compared with hiPSC-CMs
maintained on a control substrate (<0.1-mm thick 1:60 diluted Matrigel, control
hiPSC-CMs). Compared with control hiPSC-CMs, mattress hiPSC-CMs had more rod
shape morphology and significantly increased sarcomere length. Contractile
parameters of mattress hiPSC-CMs measured with video-based edge detection were
comparable with those of freshly isolated adult rabbit ventricular CMs.
Morphological and contractile properties of mattress hiPSC-CMs were consistent
across cryopreserved hiPSC-CMs generated independently at another institution.
Unlike control hiPSC-CMs, mattress hiPSC-CMs display robust contractile responses
to positive inotropic agents, such as myofilament calcium sensitizers. Mattress
hiPSC-CMs exhibit molecular changes that include increased expression of the
maturation marker cardiac troponin I and significantly increased action potential
upstroke velocity because of a 2-fold increase in sodium current (INa).
CONCLUSIONS: The Matrigel mattress method enables the rapid generation of
robustly contracting hiPSC-CMs and enhances maturation. This new method allows
quantification of contractile performance at the single-cell level, which should
be valuable to disease modeling, drug discovery, and preclinical cardiotoxicity
testing.
PMID- 26429805
TI - Looking back over 20 years of sports medicine prevention and treatment: progress,
but still a lot to achieve.
PMID- 26429806
TI - Response to: 'The search for size: a doping risk factor in adolescent rugby'.
PMID- 26429807
TI - Exercise genomics--a paradigm shift is needed: a commentary.
AB - The overarching goal of exercise genomics is to illuminate exercise biology and
behaviour in order to better understand the preventive and therapeutic values of
exercise. An ancillary aim is to understand the role of genomic variation in
human physical attributes and sports performance. The aim of this report is to
briefly comment on the current status of exercise genetics and genomics and to
suggest potential improvements to the research agenda and translational
activities. First, the genomic features of interest to the biology of exercise
are defined. Then, the limit of the current focus on common variants and their
implications for exercise genomics is highlighted. The need for a major paradigm
shift in exercise genomics research is discussed with an emphasis on study
designs and appropriately powered studies as well as on more mechanistic and
functional research. Finally, a summary of current practices in translational
activities compared with what best practice demands is introduced. One suggestion
is that the research portfolio of exercise genomics be composed of a larger
fraction of experimental and mechanistic investigations and a smaller fraction of
observational studies. It is also recommended that research should shift to
unbiased exploration of the genome using all the power of genomics, epigenomics
and transcriptomics in combination with large observational but preferably
experimental study designs, including Mendelian randomisation. In all cases,
emphasis on replications is of paramount importance. This represents an
extraordinary challenge that can only be met with large-scale collaborative and
multicentre research programmes.
PMID- 26429808
TI - Cognitive and physical symptoms of concussive injury in children: a detailed
longitudinal recovery study.
AB - BACKGROUND: Recovery from concussion sustained in childhood and adolescence is
poorly understood. We explored patterns of recovery for neurocognition and
postconcussive symptoms following concussion in children and adolescents.
METHODS: Using a prospective, longitudinal design, we collected baseline data on
728 children and adolescents aged 10-17 years. 10 participants sustained a
concussive injury (n=10) in the 12 months following baseline testing and they
were reviewed at day 5, 10 and 30 postconcussion. Assessments included the
CogSport for Kids computerised test battery to evaluate neurocognitive function
and self-report, and parent measures of postconcussive symptoms. At day 30,
parents also completed measures rating their child's quality of life and
executive functions. RESULTS: Children and adolescents displayed a gradual
reduction in postconcussive symptoms over the 30 days following injury. At day 5,
87% of participants were reporting physical and cognitive symptoms, with a
generalised reduction in all symptoms by day 10 (40% of participants). On the
computerised measure, reaction time was slower after concussion, but returned to
baseline levels by day 30. At day 30, 10% of participants demonstrated ongoing
postconcussive symptoms. Number of previous concussions was related to speed of
symptom resolution. CONCLUSIONS: At 5 days postconcussion, the majority of
children and adolescents experienced debilitating postconcussive symptoms.
However, by 30 days postinjury, 90% demonstrated recovery to normal for both
neurocognition and postconcussive symptoms.
PMID- 26429809
TI - Is cardiovascular screening in athletes justified? Inconsistent messages from the
American Heart Association.
PMID- 26429810
TI - Genetic defects in a His-Purkinje system transcription factor, IRX3, cause lethal
cardiac arrhythmias.
AB - AIM: Ventricular fibrillation (VF), the main cause of sudden cardiac death (SCD),
occurs most frequently in the acute phase of myocardial infarction: a certain
fraction of VF, however, develops in an apparently healthy heart, referred as
idiopathic VF. The contribution of perturbation in the fast conduction system in
the ventricle, the His-Purkinje system, for idiopathic VF has been implicated,
but the underlying mechanism remains unknown. Irx3/IRX3 encodes a transcription
factor specifically expressed in the His-Purkinje system in the heart. Genetic
deletion of Irx3 provides a mouse model of ventricular fast conduction
disturbance without anatomical or contraction abnormalities. The aim of this
study was to examine the link between perturbed His-Purkinje system and
idiopathic VF in Irx3-null mice, and to search for IRX3 genetic defects in
idiopathic VF patients in human. METHODS AND RESULTS: Telemetry electrocardiogram
recording showed that Irx3-deleted mice developed frequent ventricular
tachyarrhythmias mostly at night. Ventricular tachyarrhythmias were enhanced by
exercise and sympathetic nerve activation. In human, the sequence analysis of
IRX3 exons in 130 probands of idiopathic VF without SCN5A mutations revealed two
novel IRX3 mutations, 1262G>C (R421P) and 1453C>A (P485T). Ventricular
fibrillation associated with physical activities in both probands with IRX3
mutations. In HL-1 cells and neonatal mouse ventricular myocytes, IRX3
transfection up-regulated SCN5A and connexin-40 mRNA, which was attenuated by
IRX3 mutations. CONCLUSION: IRX3 genetic defects and resultant functional
perturbation in the His-Purkinje system are novel genetic risk factors of
idiopathic VF, and would improve risk stratification and preventive therapy for
SCD in otherwise healthy hearts.
PMID- 26429812
TI - SPVS calls for vets to be returned to the occupational shortage list.
PMID- 26429811
TI - A GWAS SNP for Schizophrenia Is Linked to the Internal MIR137 Promoter and
Supports Differential Allele-Specific Expression.
AB - Single nucleotide polymorphisms (SNPs) within the MIR137 gene locus have been
shown to confer risk for schizophrenia through genome-wide association studies
(GWAS). The expression levels of microRNA-137 (miR-137) and its validated gene
targets have also been shown to be disrupted in several neuropsychiatric
conditions, including schizophrenia. Regulation of miR-137 expression is thus
imperative for normal neuronal functioning. We previously characterized an
internal promoter domain within the MIR137 gene that contained a variable number
tandem repeat (VNTR) polymorphism and could alter the in vitro levels of miR-137
in a stimulus-induced and allele-specific manner. We now demonstrate that
haplotype tagging-SNP analysis linked the rs1625579 GWAS SNP for schizophrenia to
this internal MIR137 promoter through a proxy SNP rs2660304 located at this
domain. We postulated that the rs2660304 promoter SNP may act as predisposing
factor for schizophrenia through altering the levels of miR-137 expression in a
genotype-dependent manner. Reporter gene analysis of the internal MIR137 promoter
containing the common VNTR variant demonstrated genotype-dependent differences in
promoter activity with respect to rs2660304. In line with previous reports, the
major allele of the rs2660304 proxy SNP, which has previously been linked with
schizophrenia risk through genetic association, resulted in downregulation of
reporter gene expression in a tissue culture model. The genetic influence of the
rs2660304 proxy SNP on the transcriptional activity of the internal MIR137
promoter, and thus the levels of miR-137 expression, therefore offers a distinct
regulatory mechanism to explain the functional significance of the rs1625579 GWAS
SNP for schizophrenia risk.
PMID- 26429813
TI - Veterinary contributions to the elimination of rabies.
PMID- 26429814
TI - Change and challenges during a presidential year.
PMID- 26429816
TI - Vets suspended from the RCVS Register for lying about a fatal operation.
PMID- 26429817
TI - RCVS begins audit of vets' CPD compliance.
PMID- 26429818
TI - Pet identification: call for harmonised rules across the EU.
PMID- 26429819
TI - Charting progress to a TB-free Wales.
PMID- 26429820
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- 26429821
TI - Coccidiosis in suckled calves at grass.
AB - Prepatent burden in calves with low coccidial oocyst counts, Lead poisoning in
cattle, Suspect Ureaplasma species infection in a day-old calf, Lamb dysentery in
a five-week-old lamb, Oedema disease in pigs. These are among matters discussed
in the disease surveillance report for June from SAC Consulting: Veterinary
Services (SAC C VS).
PMID- 26429822
TI - Building capacity to reduce biological threats in the Middle East.
PMID- 26429823
TI - Veterinary nurses and interprofessional working.
PMID- 26429824
TI - Use of stored samples and images in research.
PMID- 26429825
TI - Drenching gun injuries in cattle.
PMID- 26429833
TI - Giving something back.
AB - Gabriel Varga leads the team that developed AFSCAN--the African Small Companion
Animal Network, which aims to 'transform the veterinary landscape across Africa'.
Dr Varga's veterinary journey began in Kosice, which at the time was part of
Czechoslovakia; he is now director of business operations for Zoetis north
Europe.
PMID- 26429834
TI - A Systematic Review of the Literature on the Sustainability of Community Health
Collaboratives.
AB - Recent interest in community health collaboratives has been driven by the
potential of these types of organizations to solve complex health problems at the
local level by bringing together stakeholders that have traditionally operated
independently, and often at cross-purposes. Much of the work that is central to
the mission of collaboratives can take years to reach fruition, however, and
there are a number of challenges to sustaining their activities. In this article,
we systematically reviewed the theoretical and empirical literature on health
care collaborative sustainability, focusing on definitions and antecedents of
sustainability. Given the diversity and fragmentation of this literature, we used
this review as a foundation to develop a synthesized definition, conceptual
groups of antecedents, and potential research propositions to help guide future
research, planning, and practice of sustainable community health collaboratives.
PMID- 26429835
TI - Deliberation Makes a Difference: Preparation Strategies for TeamSTEPPS
Implementation in Small and Rural Hospitals.
AB - Small and rural hospitals face special challenges to implement and sustain
organization-wide quality improvement (QI) initiatives due to limited resources
and infrastructures. We studied the implementation of TeamSTEPPS, a national QI
initiative, in 14 critical access hospitals. Drawing on QI and organization
development theories, we propose five strategic preparation steps for TeamSTEPPS:
assess needs, reflect on the context, set goals, develop a shared understanding,
and select change agents. We explore how hospitals' practices correspond to
suggested best practices by analyzing qualitative data collected through
quarterly interviews with key informants. We find that the level of deliberation
was a key factor that differentiated hospitals' practices. Hospitals that were
more deliberate in preparing for the five strategic steps were more likely to
experience engagement, perceive efficacy, foresee and manage barriers, and
achieve progress during implementation. We discuss potential steps that hospitals
may take to better prepare for TeamSTEPPS implementation.
PMID- 26429837
TI - Classic Tower of Hanoi, Planning Skills, and the Indian Elderly.
AB - OBJECTIVE: Elderly populations are vulnerable to age-related cognitive decline.
Planning, a frontal lobe function, is reported to be affected in the elderly
population. There is a paucity of studies which assessed planning skills in the
elderly Indian population. The present study aimed to examine the utility of the
classic Tower of Hanoi in the assessment of planning skills of elderly Indian
subjects. METHODS: A total of 215 (60 of whom were females, all aged 55-80 years)
cognitively normal elders and 24 patients with mild Alzheimer's disease were
recruited. All subjects provided informed consent and their planning skills were
assessed using the classic Tower of Hanoi. Performance at each level was measured
by the total time taken to solve, number of moves to solve, and the number of
rule violations. Receiver operating characteristic curve analysis was
exploratively performed to test the utility of the Tower of Hanoi in
differentiating patients with mild Alzheimer's disease from those who were
cognitively normal. RESULTS: Performance measures of cognitively normal group
steeply worsened with increasing complexity. With receiver operating
characteristic curve analysis, patients with mild Alzheimer's disease were poorly
differentiated from cognitively normal group according to their Tower of Hanoi
performance. CONCLUSION: The Tower of Hanoi test is of limited value for the
assessment of planning skills in the Indian elderly population. There is a need
to modify and develop a suitable neuropsychology tool to assess the planning
skills of elderly Indian subjects and further validate it.
PMID- 26429836
TI - Antidepressant Prescription Pattern in the Presence of Medical Co-morbidity: REAP
AD 2013 Study.
AB - OBJECTIVE: To evaluate the prescription pattern of antidepressants in patients
with medical co-morbidity from major psychiatric centres in Asia. METHODS: The
Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD
2013) collected data from 42 psychiatric centres in 10 Asian countries and
regions. Antidepressant prescriptions of 2320 patients with various psychiatric
disorders were evaluated. Of these, 370 patients who had specified medical co
morbidities formed the study cohort. RESULTS: Escitalopram (20%) and mirtazapine
(20%) were the most commonly prescribed antidepressants in patients with medical
co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%).
Overall, more than half (52%; 247/476) of prescriptions comprised selective
serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of
patients received at least 1 selective serotonin reuptake inhibitor. In addition,
79% of patients were prescribed only 1 antidepressant. The mean number of
antidepressants used per patient was 1.25 (standard deviation, 0.56). There were
subtle differences in the most preferred antidepressant across medical illnesses
such as diabetes mellitus, liver dysfunction, acid peptic disease, and
cerebrovascular disease. Differences were also seen in prescription patterns
across different countries. CONCLUSION: Although selective serotonin reuptake
inhibitors formed the bulk of antidepressant prescriptions in the presence of
medical co-morbidity, mirtazapine was also commonly used in the presence of
medical co-morbidities. Specified medical morbidities do influence the selection
of antidepressants.
PMID- 26429838
TI - Frequency and Correlates of Distant Visual Impairment in Patients with
Schizophrenia, Bipolar Disorder, and Major Depressive Disorder.
AB - OBJECTIVE: Distant visual impairment in the severely mentally ill is under
researched. This study aimed to assess the frequency and correlates of distant
visual impairment in a cohort of Chinese psychiatric patients, including its
effect on their quality of life. METHODS: Adult psychiatric inpatients with
schizophrenia, bipolar disorder, and major depressive disorder consecutively
admitted to a psychiatric hospital in Beijing, China underwent assessments of
psychopathology (Brief Psychiatric Rating Scale, 16-item Quick Inventory of
Depressive Symptomatology [Self-Report]), quality of life (12-item Short-Form
Medical Outcomes Study [SF-12], 25-item National Eye Institute Visual Function
Questionnaire [NEI-VFQ25]), adverse effects (Udvalg for Kliniske Undersogelser
Side Effect Rating Scale), and presenting (as opposed to uncorrected) distant
visual acuity (Logarithm of the Minimum Angle of Resolution [LogMAR] chart with
patients wearing spectacles, if they owned them). Distant visual impairment was
defined as binocular distant visual acuity of a LogMAR score of >= 0.5 (< 6/18
Snellen acuity). RESULTS: Among 356 patients who met the study criteria, the
frequency of distant visual impairment was 12.6% (15.2% with schizophrenia, 11.9%
with bipolar disorder, 8.8% with major depressive disorder). In multiple logistic
regression analysis, distant visual impairment was significantly associated with
ocular disease only (p = 0.002, odds ratio = 3.2, 95% confidence interval = 1.5
6.7). Controlling for the confounding effect of ocular disease, patients with
distant visual impairment had a lower quality of life in the general vision
domain of the NEI-VFQ25 (F[2, 353] = 9.5, p = 0.002) compared with those without.
No differences in the physical and mental domains of the SF-12 and in other
domains of the NEI-VFQ25 were noted in these 2 groups. CONCLUSION: One-eighth of
middle-aged severely mentally ill patients had distant visual impairment.
Considering the impact of distant visual impairment on daily functioning,
severely mentally ill patients need to be screened for impaired eyesight as part
of their comprehensive health assessment.
PMID- 26429839
TI - Homelessness and Cognitive Impairment: An Exploratory Study in Tokyo, Japan.
AB - OBJECTIVE: Homelessness has frequently been associated with neuropsychological
impairment. This has been observed using general screening tests for dementia as
well as tests of more focal abilities, particularly executive function. Most
studies have been of homeless individuals from North America with none reported
from Japan. METHODS: In this exploratory study we interviewed a sample of 16
homeless adults from Tokyo, Japan, and performed tests of cognitive function,
assessed head injury, addictive behaviours (drug use, gambling, alcohol abuse),
and recorded details of homelessness history. The cognitive examination involved
the Japanese Adult Reading Test to estimate premorbid intelligence quotient, the
Wisconsin Card Sorting Test to measure frontal lobe-related cognitive function,
and the Mini-Mental State Examination to measure global cognitive impairment
associated with dementia. RESULTS: Among the 16 homeless individuals, 7 (44%)
displayed global cognitive impairment. In addition, executive function tended to
be poor. In contrast, estimated premorbid intelligence quotient was within the
normal range. Substance abuse in general was not at a level to cause clinical
concern, although a high level of pathological gambling was observed. There were
no associations between cognitive function and clinical and addictive behaviour
variables, although associations were noted between cognitive scores and time
spent homeless. CONCLUSION: The results suggest high levels of neuropsychological
impairment in this sample of homeless adults in Japan. Furthermore, cognitive
impairment is acquired rather than developmental in origin, and is proportional
to the length of time spent homeless.
PMID- 26429840
TI - Psychiatric Morbidity in Chinese Adults with Type 1 Diabetes in Hong Kong.
AB - OBJECTIVES: To determine the prevalence of psychiatric morbidity and identify the
correlates, as well as to evaluate the effectiveness of the Hospital Anxiety and
Depression Scale and the 12-item General Health Questionnaire to screen for
psychiatric morbidity in Chinese adults with type 1 diabetes. METHODS: Subjects
were recruited from a local public diabetes specialist outpatient clinic from
August 2013 to January 2014. Demographic and clinical factors were recorded.
Psychiatric diagnosis was established using the Chinese-bilingual version of the
Structured Clinical Interview for the DSM-IV Axis I disorders. Scores for the
Hospital Anxiety and Depression Scale and the 12-item General Health
Questionnaire were compared with the psychiatric diagnosis. RESULTS: Of the 136
patients, the point prevalence of overall psychiatric, depressive, and anxiety
disorders was 39.7%, 23.5%, and 25.7%, respectively. Family history of mental
illness, smoking status, history of mental illness, presence of social problems,
perceived absence of confidant, presence of neuropathy and hyperlipidaemia, as
well as higher level of glycosylated haemoglobin were found to be the associated
factors. CONCLUSION: Psychiatric disorders were common in Chinese adults with
type 1 diabetes. Finding out associated factors and using the Hospital Anxiety
and Depression Scale and the 12-item General Health Questionnaire as a screening
tool helped to identify patients in a diabetes clinic with psychiatric disorders.
PMID- 26429841
TI - Is Add-on Psycho-education Effective in the Treatment of Depression?
PMID- 26429842
TI - Authors' reply.
PMID- 26429843
TI - The Best and the Brightest: 40 under 40.
PMID- 26429844
TI - Highlights from the Current Issue: October 2015.
PMID- 26429845
TI - Interpretation of Coronary Angiograms Recorded Using Google Glass: A Comparative
Analysis.
AB - INTRODUCTION: Google Glass (Google, Inc) is a voice-activated, hands-free,
optical head-mounted display device capable of taking pictures, recording videos,
and transmitting data via wi-fi. In the present study, we examined the accuracy
of coronary angiogram interpretation, recorded using Google Glass. METHODS:
Google Glass was used to record 15 angiograms with 17 major findings and the
participants were asked to interpret those recordings on: (1) an iPad (Apple,
Inc); or (2) a desktop computer. Interpretation was compared with the original
angiograms viewed on a desktop. Ten physicians (2 interventional cardiologists
and 8 cardiology fellows) participated. One point was assigned for each correct
finding, for a maximum of 17 points. RESULTS: The mean angiogram interpretation
score for Google Glass angiogram recordings viewed on an iPad or a desktop vs the
original angiograms viewed on a desktop was 14.9 +/- 1.1, 15.2 +/- 1.8, and 15.9
+/- 1.1, respectively (P=.06 between the iPad and the original angiograms, P=.51
between the iPad and recordings viewed on a desktop, and P=.43 between the
recordings viewed on a desktop and the original angiograms). In a post-study
survey, one of the 10 physicians (10%) was "neutral" with the quality of the
recordings using Google Glass, 6 physicians (60%) were "somewhat satisfied," and
3 physicians (30%) were "very satisfied." CONCLUSION: This small pilot study
suggests that the quality of coronary angiogram video recordings obtained using
Google Glass may be adequate for recognition of major findings, supporting its
expanding use in telemedicine.
PMID- 26429846
TI - Heads Up! Introducing Wearable Health Technologies in Cardiology.
PMID- 26429847
TI - ECMO and the Intraaortic Balloon Pump: In Search of the Ideal Mechanical
Circulatory Support Device.
PMID- 26429848
TI - Evaluation of the Safety of Everolimus-Eluting Bioresorbable Vascular Scaffold
(BVS) Implantation in Patients With Chronic Total Coronary Occlusions: Acute
Procedural and Short-Term Clinical Results.
AB - AIMS: The bioresorbable vascular scaffold (BVS) (Abbott Vascular) provides
temporary scaffolding while eluting everolimus. There are limited data on its use
in daily practice, especially in patients with stable angina pectoris referred
for elective percutaneous coronary intervention (PCI) of chronic total occlusions
(CTOs). The current study aims to investigate the safety and efficacy of BVS
implantation in a selected patient cohort with CTO. METHODS: A total of 70
consecutive patients, who underwent successful recanalization of CTO with BVS
between September 13, 2012 and September 20, 2014 in three cardiac centers
(Department of Cardiology, Bezmialem Vakif University, Istanbul, Turkey;
Department of Interventional Cardiology, San Raffaele Hospital, Milan, Italy; and
EMO-GVM Centro Cuore Columbus, Milan, Italy) were included in this CTO registry.
Endpoints analyzed included: (1) the composite of all-cause death and non-fatal
myocardial infarction (MI); and (2) the composite safety endpoint of major
adverse cardiovascular events (MACEs), including death, MI and symptom-driven
target lesion revascularization (TLR). RESULTS: Clinical data were obtained for
70 patients (mean age, 56.9 +/- 9.4 years; 90.0% male) with a total number of 76
CTOs. At a median follow-up of 11.0 months (interquartile range, 7-18 months),
both MACE and TLR rates were 4.3%. Two patients suffered from ischemia-driven TLR
(1 patient at 6 months and 1 patient at 9 months after implantation). No death,
MI, or stent thrombosis was observed during the follow-up period. CONCLUSION:
Treatment of CTOs with BVS seems to be safe and effective, with a high technical
success rate and acceptable MACE at short-term follow-up.
PMID- 26429849
TI - Transcatheter Aortic Valve Implantation in Patients of Extreme Age: Age is Just a
Number.
PMID- 26429850
TI - Physiologic Guidance of Infrainguinal Vascular Interventions Using the Pressure
Wire.
AB - OBJECTIVES: To assess the relationship between the resting (RG) and hyperemic
(HG) translesional peripheral gradients, with the functional and anatomic
parameters before and after an infrainguinal endovascular procedure. BACKGROUND:
RGs and HGs are objective tools in defining the hemodynamic significance of an
arterial stenosis. METHODS: In 25 subjects with infrainguinal arterial stenosis,
RG and HG were measured via a pressure wire before and after angioplasty. Before
and after the procedure, all subjects had an ankle-brachial index (ABI) and
Duplex ultrasound evaluation, recording prelesion and in-lesion peak systolic
velocity (PSV-L), and calculating a peak systolic velocity ratio (PSV-R). A
Pearson R correlation coefficient was calculated. RESULTS: The mean age was 73 +/
12 years, 70% were men, median Rutherford class 3. At baseline and after
angioplasty, mean ABI was 0.78 +/- 0.2 and 0.99 +/- 0.1, mean PSV-L was 459 +/-
110 cm/s and 126 +/- 35 cm/s, and mean PSV-R was 6.7 +/- 4 and 1.2 +/- 0.5,
respectively. RG and HG significantly improved (P<.001) from baseline to after
angioplasty (28.7 +/- 20.5 mm Hg to 5 +/- 13 mm Hg and 40.2 +/- 21.4 mm Hg to 10
+/- 13 mm Hg, respectively). RG before and after the procedure correlated well
with ABI (r = -0.58; r = -0.41), PSV-L (r = 0.40; r = 0.52), and PSV-R (r = 0.46;
r = 0.42). An improvement of 9 mm Hg in RG predicted a change of 0.1 in ABI.
CONCLUSIONS: Improvement in RG during endovascular intervention in superficial
femoral artery correlates well with the improvement in ABI, PSV-L, and PSV-R. A
postprocedural decrease in RG of 9 mm HG predicts an improvement in ABI of 0.1.
PMID- 26429851
TI - Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis:
Insights from the Atherosclerosis Lesion Progression Intervention Using Niacin
Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial.
AB - BACKGROUND: Intermediate saphenous vein graft (SVG) lesions have high rates of
progression. The purpose of this study was to examine the impact of extended
release niacin (ER-niacin) vs placebo on intermediate SVG lesions. METHODS:
Patients with intermediate (30%-60% diameter stenosis) SVG lesions were
randomized to ER-niacin vs placebo for 12 months. Quantitative coronary
angiography (QCA), intravascular ultrasonography (IVUS), and optical coherence
tomography (OCT) were performed at baseline and at 12 months. The primary
endpoint was change in percent atheroma volume (DeltaPAV). Enrollment was planned
for 138 patients for 90% power to detect >=2.5% difference in the primary
endpoint of DeltaPAV, but stopped early after publication of two negative outcome
trials of ER-niacin, with enrolled patients completing the 12-month trial
protocol. RESULTS: Thirty-eight patients were randomized to niacin (n = 19) or
placebo (n = 19), yielding power of 47% to detect the primary planned treatment
effect of 2.5 +/- 4.0% difference in DeltaPAV. Between baseline and 12-month
follow-up, no significant difference was found between study groups in DeltaPAV (
1.31 +/- 6.05% vs 1.05 +/- 17.8%; P=.60). By OCT, the ER-niacin vs placebo group
had less plaque rupture within the intermediate SVG lesion (0.0% vs 36.0%;
P=.01). CONCLUSION: Administration of ER-niacin did not significantly impact
intermediate SVG disease, with the notable limitation of compromised statistical
power due to early termination of enrollment.
PMID- 26429852
TI - Frequency, Indications, and Outcomes of Guide Catheter Extension Use in
Percutaneous Coronary Intervention.
AB - BACKGROUND: The frequency and outcomes of guide catheter extension use during
percutaneous coronary intervention (PCI) have received limited study. METHODS: We
retrospectively examined 1539 consecutive PCIs performed between May 2010 and
November 2013 to determine the frequency and outcomes of guide catheter extension
utilization. RESULTS: During the study period, a guide catheter extension was
used in 83 cases (5.4%; 95% confidence interval, 4.3%-6.6%) in 86 vessels. The
PCI target vessel was the left anterior descending artery (11%), circumflex
(23%), right coronary artery (50%), left main (1%), or a saphenous vein bypass
graft (15%). The indications for use (non-mutually exclusive) were to facilitate
equipment delivery or provide vessel support/ engagement (84.7%), thrombus
aspiration (10.5%), retrieval of lost devices (2.3%), facilitation of reverse
controlled antegrade and retrograde tracking and dissection (1%), and selective
vessel visualization with contrast (1%). Guide catheter extension success rate
was 73.3% and technical and procedural success rates were 91.6% and 90.4%,
respectively. Four patients (4.8%) experienced a guide catheter extension-related
complication: vessel dissection/injury in 2 cases (1 case required emergency
coronary artery bypass graft surgery and 1 case required stenting) and equipment
loss in 2 cases (1 detachment of the distal guide-extension marker and 1 shearing
of a guidewire tip that embolized to the renal artery). CONCLUSIONS: In a
contemporary patient population undergoing PCI, a guide catheter extension was
used in approximately 1 of 20 PCIs. Guide catheter extensions can facilitate
procedural success, but also carry low risk for device-related complications.
PMID- 26429853
TI - TAVR Through Heavily Calcified Aorta Following Atheroma Retrieval With the
"Elevator" Technique.
AB - An 86-year-old Caucasian female with severe symptomatic, inoperable aortic
stenosis was accepted for high-risk transfemoral transcatheter aortic valve
replacement (TAVR) approach due to severe calcification of the aorta. During
initial passage of a 22 Fr sheath, there was dislodgment with proximal migration
of a circumferential tunnel of calcium from the infrarenal aorta. A novel
"elevator" technique was used to secure and retrieve the dislodged aorta en bloc
back to its original infrarenal aortic position and allow in situ fixation with
stenting. A new TAVR system was then successfully placed through the stent and a
23 mm Edwards Sapien valve (Edwards Lifesciences) was implanted as planned. In
case of calcification protruding into the lumen of the aorta and limiting the
passage of the large valve delivery system sheath, the obstruction can be managed
by stenting the calcification against the luminal wall under fluoroscopic and
intravascular-ultrasound guidance, allowing successful passage of the valve
delivery system. The elevator technique allows axial transportation of any
calcified vascular fragments, should they become dislodged.
PMID- 26429854
TI - First Reported Successful Femoral Valve-in-Valve Transcatheter Aortic Valve
Replacement Using the Edwards Sapien 3 Valve.
AB - OBJECTIVES: Management of degenerated aortic valve bioprosthesis classically
requires redo surgery, but transcatheter aortic valve-in-valve implantation is
becoming a valid alternative in selected cases. In the case of a degenerated
Mitroflow bioprosthesis, TAVR is associated with an additional challenge due to a
specific risk of coronary occlusion. We aimed to assess the safety and
feasibility of transfemoral valve-in-valve implantation of the new Edwards Sapien
3 (Edwards Lifesciences) in a degenerated Mitroflow bioprosthesis (Sorin Group,
Inc). METHODS: We report here the safety and feasibility of transfemoral valve-in
valve implantation of a 23 mm Edwards Sapien 3 in a degenerated 25 mm Mitroflow
valve and describe the specific assessment of the risk of coronary obstruction
using a multi-imaging modality. RESULTS: The final result showed an absence of
aortic regurgitation and a mean transvalvular gradient of 14 mm Hg. The patient
had no major adverse cardiovascular events at 30-day follow-up. CONCLUSION:
Transcatheter valve-in-valve implantation of an Edwards Sapien 3 in a degenerated
Mitroflow is feasible and safe, considering a careful assessment of the risk of
coronary obstruction with Mitroflow bioprosthesis due to leaflets mounted
externally to the stent.
PMID- 26429855
TI - Chordal Rupture Following MitraClip Implantation Resulting in Massive Mitral
Regurgitation.
AB - MitraClip (Abbott Vascular) therapy has been reported to be a safe and effective
treatment for mitral regurgitation, even when the commissures are targeted.
However, complications during the procedure may occur. We present a 44-year-old
patient who underwent MitraClip implantation complicated by chordal rupture,
resulting in emergent mitral valve replacement.
PMID- 26429856
TI - Paravalvular Regurgitation After TAVR: Time Heals, or Not?
PMID- 26429857
TI - The New Occlutech Duct Occluder.
PMID- 26429858
TI - Palpation Versus Ultrasound in Femoral Artery Catheterization: Figure Error
Notification.
PMID- 26429860
TI - Focused ultrasound enhanced molecular imaging and gene therapy for multifusion
reporter gene in glioma-bearing rat model.
AB - The ability to monitor the responses of and inhibit the growth of brain tumors
during gene therapy has been severely limited due to the blood-brain barrier
(BBB). A previous study has demonstrated the feasibility of noninvasive in vivo
imaging with 123I-2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyluracil (123I
FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk)
cancer gene expression in an experimental animal model. Here, we tested the
enhancement of SPECT with 123I-FIAU and ganciclovir (GCV) treatment in brain
tumors after BBB disruption induced by focused ultrasound (FUS) in the presence
of microbubbles. We established an orthotopic F98 glioma-bearing rat model with
trifusion reporter genes. The results of this study showed that the rat model of
HSV1-tk-expressing glioma cells could be successfully detected by SPECT imaging
after FUS-induced BBB disruption on day 10 after implantation. Compared to the
control group, animals receiving the GCV with or without sonication exhibited a
significant antitumor activity (P < 0.05) of glioma cells on day 16 after
implantation. Moreover, combining sonication with GCV significantly inhibited
tumor growth compared with GCV alone. This study demonstrated that FUS may be
used to deliver a wide variety of theranostic agents to the brain for molecular
imaging and gene therapy in brain diseases.
PMID- 26429859
TI - HDAC inhibitor AR-42 decreases CD44 expression and sensitizes myeloma cells to
lenalidomide.
AB - Multiple myeloma (MM) is a hematological malignancy of plasma cells in the bone
marrow. Despite multiple treatment options, MM is inevitably associated with drug
resistance and poor outcomes. Histone deacetylase inhibitors (HDACi's) are
promising novel chemotherapeutics undergoing evaluation in clinical trials for
the potential treatment of patients with MM. Although in preclinical studies
HDACi's have proven anti-myeloma activity, but in the clinic single-agent HDACi
treatments have been limited due to low tolerability. Improved clinical outcomes
were reported only when HDACi's were combined with other drugs. Here, we show
that a novel pan-HDACi AR-42 downregulates CD44, a glycoprotein that has been
associated with lenalidomide and dexamethasone resistance in myeloma both in
vitro and in vivo. We also show that this CD44 downregulation is in part mediated
by miR-9-5p, targeting insulin-like growth factor 2 mRNA binding protein 3
(IGF2BP3), which directly binds to CD44 mRNA and increases its stability.
Importantly, we also demonstrate that AR-42 enhances anti-myeloma activity of
lenalidomide in primary MM cells isolated from lenalidomide resistant patients
and in in vivo MM mouse model. Thus, our findings shed light on potential novel
combinatorial therapeutic approaches modulating CD44 expression, which may help
overcome lenalidomide resistance in myeloma patients.
PMID- 26429862
TI - Autophagy manages disease-associated stress granules.
PMID- 26429863
TI - Physical, Cognitive, Social, and Emotional Mediators of Activity Involvement and
Health in Later Life.
AB - The current study tests the indirect effect of activity-related physical
activity, cognitive activity, social interaction, and emotional exchange on the
relationship between activity involvement and health (physical and emotional) in
later life. Longitudinal data from the Health and Retirement Study (N = 5,442)
were used to estimate a series of linear regression models. We found significant
indirect effects for social interaction and benefit to others (emotional
exchange) on emotional health (depressive symptoms) and indirect effects for use
of body and benefit to others (physical) on physical health (frailty). The most
potent indirect effect associated with emotional and physical health was
experienced by those engaged in all four domains (use of body, use of mind,
social interaction, and benefit to others). While effect sizes are small and
results should be interpreted with caution, findings shed light on ways in which
public health interventions aimed toward increasing role engagement in later life
could be improved.
PMID- 26429864
TI - Decoding poxvirus genome.
PMID- 26429861
TI - IL-17 producing mast cells promote the expansion of myeloid-derived suppressor
cells in a mouse allergy model of colorectal cancer.
AB - Food allergy can influence the development of colorectal cancer, although the
underlying mechanisms are unclear. While mast cells (MC) store and secrete
histamine, immature myeloid cells (IMC) are the major site of histidine
decarboxylase (HDC) expression, the enzyme responsible for histamine production.
From our earlier work, we hypothesized that histamine is central to the
association between allergy and colorectal carcinogenesis through its influence
on the MC-MDSC axis. Here, we show that in wild type (WT) mice, ovalbumin (OVA)
immunization elicits a typical TH2 response. In contrast, in HDC-/- mice, the
response to OVA allergy is skewed towards infiltration by IL-17 expressing MCs.
This response is inhibited by histamine treatment. The HDC-/- allergic IL-17
expressing MCs promote MDSC proliferation and upregulation of Cox-2 and Arg-1.
OVA allergy in HDC-/- mice increases the growth of colon tumor cells in both the
MC38 tumor cell implantation model and the AOM/DSS carcinogenesis model. Taken
together, our results show that histamine represses IL-17-expressing MCs and
their subsequent activation of MDSCs, attenuating the risk of colorectal cancer
in the setting of food allergy. Targeting the MC-MDSC axis may be useful for
cancer prevention and treatment in patients, particularly in those with food
allergy.
PMID- 26429865
TI - Passive virus movements with organelle dynamics.
PMID- 26429866
TI - Architecture of viral replication factories.
PMID- 26429867
TI - High-intensity interval training-induced metabolic adaptation coupled with an
increase in Hif-1alpha and glycolytic protein expression.
AB - It is known that repeated bouts of high-intensity interval training (HIIT) lead
to enhanced levels of glycolysis, glycogenesis, and lactate transport proteins in
skeletal muscle; however, little is known about the molecular mechanisms
underlying these adaptations. To decipher the mechanism leading to improvement of
skeletal muscle glycolytic capacity associated with HIIT, we examined the role of
hypoxia-inducible factor-1alpha (Hif-1alpha), the major transcription factor
regulating the expression of genes related to anaerobic metabolism, in the
adaptation to HIIT. First, we induced Hif-1alpha accumulation using ethyl 3,4
dihydroxybenzoate (EDHB) to assess the potential role of Hif-1alpha in skeletal
muscle. Treatment with EDHB significantly increased the protein levels of Hif
1alpha in gastrocnemius muscles, accompanied by elevated expression of genes
related to glycolysis, glycogenesis, and lactate transport. Daily administration
of EDHB for 1 wk resulted in elevated glycolytic enzyme activity in gastrocnemius
muscles. Second, we examined whether a single bout of HIIT could induce Hif
1alpha protein accumulation and subsequent increase in the expression of genes
related to anaerobic metabolism in skeletal muscle. We observed that the protein
levels of Hif-1alpha and expression of the target genes were elevated 3 h after
an acute bout of HIIT in gastrocnemius muscles. Last, we examined the effects of
long-term HIIT. We found that long-term HIIT increased the basal levels of Hif
1alpha as well as the glycolytic capacity in gastrocnemius muscles. Our results
suggest that Hif-1alpha is a key regulator in the metabolic adaptation to high
intensity training.
PMID- 26429868
TI - In vivo maximal fascicle-shortening velocity during plantar flexion in humans.
AB - Interindividual variability in performance of fast movements is commonly
explained by a difference in maximal muscle-shortening velocity due to
differences in the proportion of fast-twitch fibers. To provide a better
understanding of the capacity to generate fast motion, this study aimed to 1)
measure for the first time in vivo the maximal fascicle-shortening velocity of
human muscle; 2) evaluate the relationship between angular velocity and fascicle
shortening velocity from low to maximal angular velocities; and 3) investigate
the influence of musculo-articular features (moment arm, tendinous tissues
stiffness, and muscle architecture) on maximal angular velocity. Ultrafast
ultrasound images of the gastrocnemius medialis were obtained from 31
participants during maximal isokinetic and light-loaded plantar flexions. A
strong linear relationship between fascicle-shortening velocity and angular
velocity was reported for all subjects (mean R(2) = 0.97). The maximal shortening
velocity (V(Fmax)) obtained during the no-load condition (NLc) ranged between
18.8 and 43.3 cm/s. V(Fmax) values were very close to those of the maximal
shortening velocity (V(max)), which was extrapolated from the F-V curve (the Hill
model). Angular velocity reached during the NLc was significantly correlated with
this V(Fmax) (r = 0.57; P < 0.001). This finding was in agreement with
assumptions about the role of muscle fiber type, whereas interindividual
comparisons clearly support the fact that other parameters may also contribute to
performance during fast movements. Nevertheless, none of the biomechanical
features considered in the present study were found to be directly related to the
highest angular velocity, highlighting the complexity of the upstream mechanics
that lead to maximal-velocity muscle contraction.
PMID- 26429869
TI - Eccentric exercise slows in vivo microvascular reactivity during brief
contractions in human skeletal muscle.
AB - Unaccustomed exercise involving eccentric contractions results in muscle soreness
and an overall decline in muscle function, however, little is known about the
effects of eccentric exercise on microvascular reactivity in human skeletal
muscle. Fourteen healthy men and women performed eccentric contractions of the
dorsiflexor muscles in one leg, while the contralateral leg served as a control.
At baseline, and 24 and 48 h after eccentric exercise, the following were
acquired bilaterally in the tibialis anterior muscle: 1) transverse relaxation
time (T2)-weighted magnetic resonance images to determine muscle cross-sectional
area (mCSA) and T2; 2) blood oxygen level-dependent (BOLD) images during and
following brief, maximal voluntary contractions (MVC) to monitor the hyperemic
responses with participants positioned supine in a 3T magnet; 3) muscle strength;
and 4) pain pressure threshold. Compared with the control leg, eccentric exercise
resulted in soreness, decline in strength (~20%), increased mCSA (~7%), and
prolonged T2 (~7%) at 24 and 48 h (P < 0.05). The BOLD response to a brief MVC
was altered 24 and 48 h after eccentric exercise, such that time-to-peak (~35%, P
< 0.05) and time-to-half-recovery (~23%, P < 0.05) were prolonged. The altered
contraction-induced hyperemic response suggests slowed microvascular reactivity
and altered matching of O2 delivery to O2 utilization within muscle tissue
showing signs of muscle damage. These changes in microvascular regulation after
eccentric exercise may impede rapid adjustments in muscle blood flow at exercise
onset and during activities involving brief bursts of muscle activation, which
may impair O2 delivery and contribute to reduced muscle function after eccentric
exercise.
PMID- 26429870
TI - Cardiorespiratory and sensory responses to exercise in adults with mild cystic
fibrosis.
AB - The purpose of this study was to evaluate cardiorespiratory fitness and reasons
for exercise curtailment in a contemporary adult cystic fibrosis (CF) cohort with
mild lung disease. Adults with mild CF (n = 19, forced expiratory volume in 1 s =
95 +/- 17% predicted) were age-, sex-, ethnicity-, and body mass index-matched to
healthy controls (n = 19) and underwent a detailed cardiopulmonary cycle exercise
test. While CF subjects had a reduced peak oxygen uptake compared with controls,
the values were normal when expressed as %predicted in 14/19 (74%) of subjects.
Both groups demonstrated a normal cardiovascular limitation to exercise and
stopped exercise primarily because of leg fatigue. Despite not being exercise
limited by respiratory factors, there was some evidence of ventilatory
abnormalities as patients with mild CF had increased end-inspiratory lung volumes
and reached an inflection/plateau in tidal volume relative to minute ventilation
at lower exercise intensities compared with controls. Subjects with CF were not
more likely to demonstrate expiratory flow limitation compared with controls and
did not have evidence of dynamic hyperinflation during exercise. Despite
increased end-inspiratory lung volumes and an earlier tidal volume
inflection/plateau, CF subjects did not experience higher levels of dyspnea. In
an exploratory analysis, a significant inverse correlation was observed between
sweat chloride and peak work rate. Adult CF subjects with relatively well
preserved spirometry have normal exercise performance relative to reference
values and are primarily limited by nonrespiratory factors. However, ventilatory
abnormalities were detected even in this mild CF cohort and should be evaluated
in future therapeutic trials focused on disease-modifying therapies in mild CF.
PMID- 26429871
TI - Good syndrome presenting with CD8+ T-Cell large granular lymphocyte leukemia.
AB - Good Syndrome is an adult-onset combined immunodeficiency defined by
hypogammaglobulinemia, low or absent number of B cells, T cell deficiency and
thymic tumor. We have characterized CD8+ T cells from a patient with Good
syndrome that presented with CD8+T-cell large granular lymphocytic leukemia
(LGL). Characterization of peripheral blood CD8+ T cells revealed that majority
of CD8+ T cells were terminally differentiated effector memory phenotype (TEMRA;
CD8+CCR7-CD45RA+), and were PD-1high (CD279), ICOSlow (CD278), and granzymehigh.
Almost all CD8+ T cells were IFN-gamma+. CD8 Treg (CD8+CD183+CCR7+CD45RA-) were
decreased. TEMRA phenotype along with CD279high, demonstrates that these are
exhausted CD8+ T cells. This phenotype along with CD278low may also explain
severe T cell functional deficiency in our patient. In the present patient, T-LGL
appears to be a clonal expansion of CD279+granzyme+IFN-gamma+CD8+TEMRA cells. To
best of our knowledge this is the first case of CD8+T-cell LGL leukemia
associated with Good syndrome.
PMID- 26429872
TI - Application of functional vincristine plus dasatinib liposomes to deletion of
vasculogenic mimicry channels in triple-negative breast cancer.
AB - Standard chemotherapy cannot eradicate triple-negative breast cancer (TNBC) while
the residual cancer cells readily form the vasculogenic mimicry (VM) channels,
which lead to the relapse of cancer after treatment. In this study, the
functional vincristine plus dasatinib liposomes, modified by a targeting molecule
DSPE-PEG2000-c(RGDyK), were fabricated to address this issue. The investigations
were performed on TNBC MDA-MB-231 cells and MDA-MB-231 xenografts in nude mice.
The liposomes exhibited the superior performances in the following aspects: the
enhancement of cellular uptake via targeted action; the induction of apoptosis
via activation of caspase 8, 9, and 3, increased expression of Bax, decreased
expression of Mcl-1, and generation of reactive oxygen species (ROS); and the
deletion of VM channels via inhibitions on the VM channel indicators, which
consisted of vascular endothelial-cadherin (VE-Cad), focal adhesion kinase (FAK),
phosphatidylinositide 3-kinase (PI3K), and matrix metallopeptidases (MMP-2, and
MMP-9). Furthermore, the liposomes displayed the prolonged circulation time in
the blood, the increased accumulation in tumor tissue, and the improved
therapeutic efficacy along with deletion of VM channels in the TNBC-bearing mice.
In conclusion, the nanostructured functional drug-loaded liposomes may provide a
promising strategy for the treatment of invasive TNBC along with deletion of VM
channels.
PMID- 26429873
TI - Genomic landscape of endometrial stromal sarcoma of uterus.
AB - Although recurrent gene fusions such as JAZF1-JJAZ1 are considered driver events
for endometrial stromal sarcoma (ESS) development, other genomic alterations
remain largely unknown. In this study, we performed whole-exome sequencing,
transcriptome sequencing and copy number profiling for five ESSs (three low-grade
ESS (LG-ESS) and two undifferentiated uterine sarcomas (UUSs)). All three LG-ESSs
exhibited either one of JAZF1-SUZ12, JAZF1-PHF1 and MEAF6-PHF1 fusions, whereas
the two UUSs did not. All ESSs except one LG-ESS exhibited copy number
alterations (CNAs), many of which encompassed cancer-related genes. In UUSs, five
CNAs encompassing cancer-related genes (EZR, CDH1, RB1, TP53 and PRKAR1A)
accompanied their expressional changes, suggesting that they might stimulate UUS
development. We found 81 non-silent mutations (35 from LG-ESSs and 46 from UUSs)
that included 15 putative cancer genes catalogued in cancer-related databases,
including PPARG and IRF4 mutations. However, they were non-recurrent and did not
include any well-known mutations, indicating that point mutations may not be a
major driver for ESS development. Our data show that gene fusions and CNAs are
the principal drivers for LG-ESS and USS, respectively, but both may require
additional genomic alterations including point mutations. These differences may
explain the different biologic behaviors between LG-ESS and UUS. Our findings
suggest that ESS development requires point mutations and CNAs as well as the
gene fusions.
PMID- 26429874
TI - URGCP/URG4 promotes apoptotic resistance in bladder cancer cells by activating NF
kappaB signaling.
AB - Cisplatin is a well-known chemotherapeutic agent, it could cause DNA damage and
induce apoptotic cell death, but the cisplatin resistance also appears, it's
important to reveal the mechanisms of cisplatin resistance [1]. URGCP/URG4 is
overexpressed in various tumors and plays critical role during tumor development.
We found URGCP/URG4 was upregulated in bladder cancer cells and tissues,
URGCP/URG4 overexpression increased the resistance to cisplatin-induced apoptosis
in bladder cancer, and promoted anti-apoptotic genes expression, such as Bcl-2,
Survivin, MCL-1, FLIP, and downregulated Caspase-3 expression, Knockdown of
URGCP/URG4 decreased the resistance to cisplatin-induced apoptosis, and inhibited
anti-apoptotic genes expression, such as Bcl-2, Survivin, MCL-1, FLIP, and
upregulated Caspase-3 expression. Mechanism analysis found URGCP/URG4 activated
NF-kappaB pathway which is a well-known anti-apoptotic pathway and promoted the
expression of NF-kappaB targeted genes. So we speculated URGCP/URG4 regulates
cisplatin-induced apoptosis by activating NF-kappaB pathway. We also analyzed the
correlation between URGCP/URG4 expression and clinical clinicopathologic, and
found its expression was positively correlated with bladder cancer progression,
it can serve as a valuable prognostic factor. In summary, URGCP/URG4 promotes the
resistance to cisplatin-induced apoptosis by activating NF-kappaB pathway, and is
an unfavorable prognostic factor for bladder cancer.
PMID- 26429875
TI - URGCP promotes non-small cell lung cancer invasiveness by activating the NF
kappaB-MMP-9 pathway.
AB - Invasion and metastasis are main traits of tumor progression and responsible for
the poor prognosis of advanced non-small cell lung cancer (NSCLC). The molecular
mechanisms underlying the malignant behaviors of NSCLC remain incompletely
understood. The present study demonstrate that up-regulator of cell proliferation
(URGCP), a recently identified tumor-promoting gene found in several tumor types,
is markedly overexpressed in human NSCLC cell lines and clinical NSCLC samples.
URGCP upregulation correlates significantly with the progression and poor
prognosis of this disease. In vitro and in vivo studies demonstrate that
increasing URGCP expression accelerates invasion, migration, and distant
metastasis of NSCLC cells whereas downregulating URGCP suppresses these malignant
traits. Notably, silencing URGCP expression almost completely abrogates the
metastatic ability of NSCLC cells. At the molecular level, URGCP markedly
promotes MMP-9 expression by activating NF-kappaB signaling. Additionally, URGCP
and MMP-9 expression are positively correlated in various cohorts of human NSCLC
specimens, and NF-kappaB-activated MMP-9 expression contributes to URGCP-induced
invasiveness of NSCLC cell lines. Collectively, these findings indicate that
URGCP plays an important role in promoting NSCLC cell invasion and metastasis by
enhancing NF-kappaB-activated MMP-9 expression and may serve as a potential
therapeutic target and prognostic marker.
PMID- 26429876
TI - IGK with conserved IGKappaV/IGKappaJ repertoire is expressed in acute myeloid
leukemia and promotes leukemic cell migration.
AB - We have previously reported that immunoglobulin heavy chain genes were expressed
in myeloblasts and mature myeloid cells. In this study, we further demonstrated
that rearranged Ig kappa light chain was also frequently expressed in acute
myeloid leukemia cell lines (6/6), primary myeloblasts from patients with acute
myeloid leukemia (17/18), and mature monocytes (11/12) and neutrophils (3/12)
from patients with non-hematopoietic neoplasms, but not or only rarely expressed
in mature neutrophils (0/8) or monocytes (1/8) from healthy individuals.
Interestingly, myeloblasts and mature monocytes/neutrophils shared several
restricted IGKV and IGKJ gene usages but with different expression frequency.
Surprisingly, almost all of the acute myeloid leukemia-derived IGKV showed
somatic hypermutation; in contrast, mature myeloid cells-derived IGKV rarely had
somatic hypermutation. More importantly, although IGK expression appeared not to
affect cell proliferation, reduced IGK expression led to a decrease in cell
migration in acute myeloid leukemia cell lines HL-60 and NB4, whereas increased
IGK expression promoted their motility. In summary, IGK is expressed in
myeloblasts and mature myeloid cells from patients with non-hematopoietic
neoplasms, and is involved in cell migration. These results suggest that myeloid
cells-derived IgK may have a role in leukemogenesis and may serve as a novel
tumor marker for monitoring minimal residual disease and developing target
therapy.
PMID- 26429878
TI - Parsimonious covariate selection for a multicategory ordered response.
AB - We propose a flexible continuation ratio (CR) model for an ordinal categorical
response with potentially ultrahigh dimensional data that characterizes the
unique covariate effects at each response level. The CR model is the logit of the
conditional discrete hazard function for each response level given covariates. We
propose two modeling strategies, one that keeps the same covariate set for each
hazard function but allows regression coefficients to arbitrarily change with
response level, and one that allows both the set of covariates and their
regression coefficients to arbitrarily change with response. Evaluating a
covariate set is accomplished by using the nonparametric bootstrap to estimate
prediction error and their robust standard errors that do not rely on proper
model specification. To help with interpretation of the selected covariate set,
we flexibly estimate the conditional cumulative distribution function given the
covariates using the separate hazard function models. The goodness-of-fit of our
flexible CR model is assessed with graphical and numerical methods based on the
cumulative sum of residuals. Simulation results indicate the methods perform well
in finite samples. An application to B-cell acute lymphocytic leukemia data is
provided.
PMID- 26429877
TI - Simultaneous targeting of 5-LOX-COX and EGFR blocks progression of pancreatic
ductal adenocarcinoma.
AB - Cyclooxygenase-2 (COX-2), 5-Lipoxygenase (5-LOX), and epidermal growth factor
receptor (EGRF) are over-expressed in human pancreatic ductal adenocarcinoma
(PDAC). Using next-generation sequencing (NGS) analysis, we show significant
increase in COX-2, 5-LOX, and EGFR expression during PDAC progression. Targeting
complementary pathways will achieve better treatment efficacy than a single agent
high-dose strategy that could increase risk of side effects and tumor resistance.
To target COX-2, 5-LOX, and EGFR simultaneously, we tested effects of licofelone
(dual 5-LOX-COX inhibitor), and gefitinib (EGFR inhibitor), individually and in
combination, on pancreatic intraepithelial neoplasms (PanINs) and their
progression to PDAC using genetically engineered mice. Individually, licofelone
(L) and gefitinib (G) significantly inhibited incidence of PDAC in male (72% L,
90% G, p < 0.0001) and female (90% L, 85% G, p < 0.0001) mice. The combination
drug treatment produced complete inhibition of PDAC in both genders. Pancreata of
mice receiving combination treatment showed significantly fewer Dclk1-positive
cancer stem-like cells, inhibition of COX-2, 5-LOX, PCNA, EGFR and beta-catenin
expression (p < 0.05-0.0002), increased p21 expression. Significant changes in
tumor immune responses and desmoplastic reaction was observed by NGS analysis in
combination treatment (p < 0.05). In summary, early simultaneous targeting of 5
LOX-COX- and EGFR pathways may provide additive inhibitory effects leading to
complete suppression of PDAC.
PMID- 26429880
TI - Role of eukaryotic-like serine/threonine kinases in bacterial cell division and
morphogenesis.
AB - Bacteria possess a repertoire of versatile protein kinases modulating diverse
aspects of their physiology by phosphorylating proteins on various amino acids
including histidine, cysteine, aspartic acid, arginine, serine, threonine and
tyrosine. One class of membrane serine/threonine protein kinases possesses a
catalytic domain sharing a common fold with eukaryotic protein kinases and an
extracellular mosaic domain found in bacteria only, named PASTA for 'Penicillin
binding proteins And Serine/Threonine kinase Associated'. Over the last decade,
evidence has been accumulating that these protein kinases are involved in cell
division, morphogenesis and developmental processes in Firmicutes and
Actinobacteria. However, observations differ from one species to another
suggesting that a general mechanism of activation of their kinase activity is
unlikely and that species-specific regulation of cell division is at play. In
this review, we survey the latest research on the structural aspects and the
cellular functions of bacterial serine/threonine kinases with PASTA motifs to
illustrate the diversity of the regulatory mechanisms controlling bacterial cell
division and morphogenesis.
PMID- 26429879
TI - Extracellular vesicle-mediated transfer of CLIC1 protein is a novel mechanism for
the regulation of glioblastoma growth.
AB - Little progresses have been made in the treatment of glioblastoma (GBM), the most
aggressive and lethal among brain tumors. Recently we have demonstrated that
Chloride Intracellular Channel-1 (CLIC1) is overexpressed in GBM compared to
normal tissues, with highest expression in patients with poor prognosis.
Moreover, CLIC1-silencing in cancer stem cells (CSCs) isolated from human GBM
patients negatively influences proliferative capacity and self-renewal properties
in vitro and impairs the in vivo tumorigenic potential. Here we show that CLIC1
exists also as a circulating protein, secreted via extracellular vesicles (EVs)
released by either cell lines or GBM-derived CSCs. Extracellular vesicles (EVs),
comprising exosomes and microvesicles based on their composition and biophysical
properties, have been shown to sustain tumor growth in a variety of model
systems, including GBM. Interestingly, treatment of GBM cells with CLIC1
containing EVs stimulates cell growth both in vitro and in vivo in a CLIC1-dose
dependent manner. EVs derived from CLIC1-overexpressing GBM cells are strong
inducers of proliferation in vitro and tumor engraftment in vivo. These
stimulations are significantly attenuated by treatment of GBM cells with EVs
derived from CLIC1-silenced cells. However, CLIC1 modulation appears to have no
direct role in EV structure, biogenesis and secretion. These findings reveal
that, apart from the function of CLIC1 cellular reservoir, CLIC1 contained in EVs
is a novel regulator of GBM growth.
PMID- 26429881
TI - Metallic ground state in an ion-gated two-dimensional superconductor.
AB - Recently emerging two-dimensional (2D) superconductors in atomically thin layers
and at heterogeneous interfaces are attracting growing interest in condensed
matter physics. Here, we report that an ion-gated zirconium nitride chloride
surface, exhibiting a dome-shaped phase diagram with a maximum critical
temperature of 14.8 kelvin, behaves as a superconductor persisting to the 2D
limit. The superconducting thickness estimated from the upper critical fields is
? 1.8 nanometers, which is thinner than one unit-cell. The majority of the vortex
phase diagram down to 2 kelvin is occupied by a metallic state with a finite
resistance, owing to the quantum creep of vortices caused by extremely weak
pinning and disorder. Our findings highlight the potential of electric-field
induced superconductivity, establishing a new platform for accessing quantum
phases in clean 2D superconductors.
PMID- 26429882
TI - Direct sampling of electric-field vacuum fluctuations.
AB - The ground state of quantum systems is characterized by zero-point motion. This
motion, in the form of vacuum fluctuations, is generally considered to be an
elusive phenomenon that manifests itself only indirectly. Here, we report direct
detection of the vacuum fluctuations of electromagnetic radiation in free space.
The ground-state electric-field variance is inversely proportional to the four
dimensional space-time volume, which we sampled electro-optically with tightly
focused laser pulses lasting a few femtoseconds. Subcycle temporal readout and
nonlinear coupling far from resonance provide signals from purely virtual photons
without amplification. Our findings enable an extreme time-domain approach to
quantum physics, with nondestructive access to the quantum state of light.
Operating at multiterahertz frequencies, such techniques might also allow time
resolved studies of intrinsic fluctuations of elementary excitations in condensed
matter.
PMID- 26429883
TI - FOOD SCIENCE. Designing a sustainable diet.
PMID- 26429884
TI - A GABAergic projection from the zona incerta to cortex promotes cortical neuron
development.
AB - gamma-Aminobutyric acid (GABA) is the major inhibitory transmitter in the mature
brain but is excitatory in the developing cortex. We found that mouse zona
incerta (ZI) projection neurons form a GABAergic axon plexus in neonatal cortical
layer 1, making synapses with neurons in both deep and superficial layers. A
similar depolarizing GABAergic plexus exists in the developing human cortex.
Selectively silencing mouse ZI GABAergic neurons at birth decreased synaptic
activity and apical dendritic complexity of cortical neurons. The ZI GABAergic
projection becomes inhibitory with maturation and can block epileptiform activity
in the adult brain. These data reveal an early-developing GABAergic projection
from the ZI to cortical layer 1 that is essential for proper development of
cortical neurons and balances excitation with inhibition in the adult cortex.
PMID- 26429885
TI - A brain circuit that synchronizes growth and maturation revealed through Dilp8
binding to Lgr3.
AB - Body-size constancy and symmetry are signs of developmental stability. Yet, it is
unclear exactly how developing animals buffer size variation. Drosophila insulin
like peptide Dilp8 is responsive to growth perturbations and controls homeostatic
mechanisms that coordinately adjust growth and maturation to maintain size within
the normal range. Here we show that Lgr3 is a Dilp8 receptor. Through the use of
functional and adenosine 3',5'-monophosphate assays, we defined a pair of Lgr3
neurons that mediate homeostatic regulation. These neurons have extensive axonal
arborizations, and genetic and green fluorescent protein reconstitution across
synaptic partners show that these neurons connect with the insulin-producing
cells and prothoracicotropic hormone-producing neurons to attenuate growth and
maturation. This previously unrecognized circuit suggests how growth and
maturation rate are matched and co-regulated according to Dilp8 signals to
stabilize organismal size.
PMID- 26429887
TI - Sperm calcineurin inhibition prevents mouse fertility with implications for male
contraceptive.
AB - Calcineurin inhibitors, such as cyclosporine A and FK506, are used as
immunosuppressant drugs, but their adverse effects on male reproductive function
remain unclear. The testis expresses somatic calcineurin and a sperm-specific
isoform that contains a catalytic subunit (PPP3CC) and a regulatory subunit
(PPP3R2). We demonstrate herein that male mice lacking Ppp3cc or Ppp3r2 genes
(knockout mice) are infertile, with reduced sperm motility owing to an inflexible
midpiece. Treatment of mice with cyclosporine A or FK506 creates phenocopies of
the sperm motility and morphological defects. These defects appear within 4 to 5
days of treatment, which indicates that sperm-specific calcineurin confers
midpiece flexibility during epididymal transit. Male mouse fertility recovered a
week after we discontinued treatment. Because human spermatozoa contain PPP3CC
and PPP3R2 as a form of calcineurin, inhibition of this sperm-specific
calcineurin may lead to the development of a reversible male contraceptive that
would target spermatozoa in the epididymis.
PMID- 26429888
TI - New clues to the understanding of animal development.
PMID- 26429886
TI - Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to
establish infection.
AB - Dendritic cells can capture and transfer retroviruses in vitro across synaptic
cell-cell contacts to uninfected cells, a process called trans-infection. Whether
trans-infection contributes to retroviral spread in vivo remains unknown. Here,
we visualize how retroviruses disseminate in secondary lymphoid tissues of living
mice. We demonstrate that murine leukemia virus (MLV) and human immunodeficiency
virus (HIV) are first captured by sinus-lining macrophages. CD169/Siglec-1, an I
type lectin that recognizes gangliosides, captures the virus. MLV-laden
macrophages then form long-lived synaptic contacts to trans-infect B-1 cells.
Infected B-1 cells subsequently migrate into the lymph node to spread the
infection through virological synapses. Robust infection in lymph nodes and
spleen requires CD169, suggesting that a combination of fluid-based movement
followed by CD169-dependent trans-infection can contribute to viral spread.
PMID- 26429890
TI - Efficacy of raltegravir-containing regimens in antiretroviral-naive and
experienced individuals in routine clinical practice.
AB - Raltegravir is one of the standard antiretroviral therapy (ART) options in
treatment-experienced and -naive patients. However, efficacy data from clinical
practice are scarce. Therefore, the efficacy of raltegravir-containing ART in
clinical practice was investigated retrospectively. In all, 295 treatment-naive
and -experienced patients were analysed using two different cut-offs for
virological failure (200 or 50 copies/ml). The response at week 24 and onwards
was evaluated as a 'time to loss of virological response' analysis and estimated
as a survival function. Additionally, dual therapy regimens (raltegravir plus
boosted protease inhibitor) were compared to standard combinations in experienced
patients performing a snapshot analysis at weeks 24 and 48, as well as a time to
loss of virological response analysis. A total of 86.2% of the 64 treatment-naive
patients maintained virological suppression using a cut-off of 200 copies/ml
(c/ml), while 67.7% maintained virological suppression with a 50 copies/ml cut
off from week 24 until the end of observation. Among the 231 treatment
experienced patients, 84.8% maintained virological suppression from week 24
onwards using a cut-off of 200 copies/ml; and 71.0% using 50 copies/ml,
respectively. In the subgroup snapshot analysis at week 24, 98.3% (86.7% using a
cut-off of 50 copies/ml) and at week 48, 93.3% (80.0%) of patients responded to
dual therapy. Patients who were receiving a standard background therapy responded
in 88.3% (81.3%) at week 24 and in 86.0% (80.7%) at week 48. Differences were not
significant. This study shows again the overall long-term efficacy of raltegravir
based ART and furthermore gives reference for a comparable efficacy of dual and
standard nucleos(t)ide reverse transcriptase inhibitor-backbone regimens in
experienced patients on raltegravir over a period of 48 weeks in a real-life
cohort where patients with severe comorbidities were included.
PMID- 26429889
TI - A human laterality disorder caused by a homozygous deleterious mutation in MMP21.
AB - BACKGROUND: Laterality in the vertebrate embryo is determined by left-right
asymmetric gene expression driven by the flow of extraembryonic fluid across the
embryonic node. Defects in these processes cause heterotaxy, the abnormal
formation and arrangement of visceral organs that can range from complete
inversion of symmetry to the selective misarrangement of organs. However, our
understanding of the genetic causality for laterality defects in human beings
remains relatively limited. METHODS: We performed whole exome sequencing in a
consanguineous family with heterotaxia. To interrogate the pathogenic potential
of the discovered variant, we used an in vivo system in which the potential of
the candidate gene to induce L-R asymmetry was tested by transient suppression
and CRISPR/Cas9-induced deletions. We also used in vitro assays to test a
possible link between our exome-derived candidate and Notch signaling. RESULTS:
We identified a homozygous 2 bp deletion in MMP21, encoding matrix
metalloproteinase-21, as the sole coding mutation that segregated with the
phenotype. Transient suppression or CRISPR/Cas9-mediated deletion of mmp21 in
zebrafish embryos induced cardiac looping defects, with concomitant disruption of
laterality markers in the lateral plate mesoderm and disrupted notch signalling
in vitro and in vivo. CONCLUSIONS: Our data implicate loss of MMP21 as a cause of
heterotaxy in humans with concomitant defects in Notch signaling. In support of
this finding, a homozygous missense mutation in MMP21 was identified previously
in mice with N-Ethyl-N-Nitrosourea (ENU)-induced heterotaxy. Taken together,
these observations suggest a role of matrix metalloproteinases in the
establishment of asymmetric organ development, likely through the regulation of
morphogenetic signals.
PMID- 26429891
TI - Invasive shigellosis in MSM.
AB - Shigella flexneri is an emerging pathogen in men who have sex with men (MSM);
recent outbreaks related to sexual practices have been noted in this population
in the UK and other developed countries. While the majority of cases of
shigellosis present with gastroenteritis, some vulnerable patients with
underlying immunosuppression can develop complications like bacteraemia and may
present atypically as an acute surgical emergency. This case report highlights
such a case of S. flexneri bacteraemia in a man who had sex with men.
PMID- 26429892
TI - A national survey of nurse-led and delivered services within sexual health across
the United Kingdom.
AB - This was a cross-sectional study using an online survey to evaluate the provision
of nurse-led and delivered services within genitourinary medicine in the UK.
Results showed that such services are being widely utilised and are generally
well supported by medical staff. The delivery of nurse-led and delivered services
appears to be quite variable. Clinical guidelines and standards may help to
ensure a more uniform approach to these services and help to maintain high
standards of care.
PMID- 26429893
TI - A cross sectional survey of the barriers for implementing rapid HIV testing among
French general practitioners.
AB - In France, almost 30,000 people are unaware of their HIV-positive status.
Innovative screening strategies are essential to reach this population. The aim
of this study was to describe the acceptability of rapid HIV testing (RHT) among
French general practitioners (GPs) working in the south of France and barriers
for implementing this strategy. We analysed an anonymous questionnaire sent by
mail to GPs about demographic data, routine practice, knowledge of RHT and
barriers to its use. Between 1 April and 30 September 2013, out of the 165 GPs
contacted, 78 returned the questionnaires. The GPs' mean age was 52 years; 49
were men. Fifty-one GPs reported that their registered patients included at least
one HIV-infected person and 70 GPs reported taking care of high-risk patients.
Sixty-three percent of GPs reported being interested in using RHT in their daily
practice. The main reasons reported by uninterested GPs were: greater confidence
in standard HIV testing, difficulties including RHT during the routine
consultation, difficulties to screen for other sexually transmitted infections
simultaneously, and difficulties to deliver a positive result. French National
Authorities for Health propose to screen the population at least once in their
lifetime and high-risk people at least once a year. In order to achieve this aim,
RHT should be included in the GPs' arsenal for HIV testing. We showed a high
acceptability of RHT by GPs. If specific and adapted training is developed, and
if solutions to barriers reported by GPs are found, RHT could be implemented in
to their routine activity.
PMID- 26429894
TI - Adverse pregnancy outcomes following syphilis treatment in pregnancy in the UK.
AB - Syphilis infection in pregnancy is known to cause a number of severe adverse
pregnancy outcomes, including second-trimester miscarriage, stillbirth, very pre
term delivery and neonatal death, in addition to congenital syphilis. A
retrospective review of women with positive syphilis serology and a pregnancy
outcome between 2005 and 2012 in Leeds, UK, was performed. In all, 57 cases of
positive syphilis serology in pregnancy were identified: 24 with untreated
syphilis treated in the current pregnancy (Group 1); seven with reported but
unconfirmed prior treatment who were retreated (Group 2); and 26 adequately
treated prior to pregnancy (Group 3). The rate of severe adverse pregnancy
outcomes in Group 1 at 21% was significantly higher than the 0% outcome of Group
3 (p = 0.02). The severe adverse pregnancy outcomes were two second-trimester
miscarriages, two pre-term births at 25 and 28 weeks and one stillbirth at 32
weeks. There were no cases of term congenital syphilis or term neonatal death,
but we observed high rates of other adverse pregnancy outcomes despite treatment
during pregnancy. Rapid referral for treatment is needed before 18 weeks in order
to minimise adverse pregnancy outcomes.
PMID- 26429895
TI - A Scottish multi-centre service evaluation examining the prevalence and diagnosis
of Trichomonas vaginalis in symptomatic women attending sexual health clinics.
AB - Trichomoniasis caused by the protozoan parasite Trichomonas vaginalis (TV) is one
of the most commonly occurring sexually transmitted infections of non-viral
origin. This study examines the prevalence of TV infection amongst consenting
symptomatic women attending three of the largest sexual health clinics in
Scotland, United Kingdom. In addition, an evaluation of three testing methods to
identify TV from vaginal fluid was performed involving the commercial Hologic
APTIMA TV transcription-mediated amplification assay, a real-time PCR assay and
microscopy. A total of 398 patients consented to participation and all were
tested by the three methods. The prevalence of TV was 2.8% (n = 11), with both
molecular assays correctly detecting an additional two cases of TV compared to
microscopy. The prevalence of three other sexually transmitted pathogens, namely
Chlamydia trachomatis, Neisseria gonorrhoeae and herpes simplex virus were 7.3%
(n = 31), 0.3% (n = 1) and 1.5% (n = 6), respectively. The majority of TV cases
(78%; n = 8) occurred in women greater than 29 years of age compared to most
Chlamydia trachomatis cases, who were aged 30 or less (97%; n = 30).
PMID- 26429896
TI - Letter Regarding: Survival Analysis of the Single- and Double-Coated STAR Ankle
up to 20 Years: Long-term Follow-up of 324 Cases From the Swedish Ankle Registry.
PMID- 26429897
TI - Response to "Letter Regarding: Survival Analysis of the Single- and Double-Coated
STAR Ankle up to 20 Years: Long-term Follow-up of 324 Cases From the Swedish
Ankle Registry".
PMID- 26429898
TI - Letter Regarding: Single-Photon-Emission Computed Tomography in Painful Total
Ankle Replacements.
PMID- 26429899
TI - Response to "Letter Regarding: Single-Photon-Emission Computed Tomography in
Painful Total Ankle Replacements".
PMID- 26429900
TI - Letter Regarding: Comparison of Cannulated Screws Versus Compression Staples for
Subtalar Arthrodesis Fixation.
PMID- 26429901
TI - Response to "Letter Regarding: Comparison of Cannulated Screws Versus Compression
Staples for Subtalar Arthrodesis Fixation".
PMID- 26429903
TI - Ccn1, a molecular switch that imposes a self-limiting control on inflammation and
wound healing in a multitude of organs?
PMID- 26429904
TI - Reply to Dr. Weiskirchen.
PMID- 26429905
TI - Retraction.
AB - Foster WM, Adler KB, Crews AL, Potts EN, Fischer BM, Voynow JA. MARCKS-related
peptide modulates in vivo the secretion of airway Muc5ac. Am J Physiol Lung Cell
Mol Physiol 299: L345-L352; doi: 10.1152/ajplung.00067.2010. The authors have
discovered that Figs. 1, 2, and 6 are not reliable. We offer our sincere
apologies for the errors and for any inconvenience associated with the
publication of the article. The paper is therefore being retracted by the
American Physiological Society at the request of Dr. Voynow, and with the
approval of the coauthors.
PMID- 26429906
TI - Device therapy in cardiac disease: a success story.
PMID- 26429907
TI - Keith Fox: Caledonian collaborations and translational triumphs.
PMID- 26429908
TI - The effect of fall prevention exercise programmes on fall induced injuries in
community dwelling older adults.
AB - STUDY QUESTION: Are fall prevention exercise interventions for older people
living in the community effective in preventing different types of fall related
injuries? SUMMARY ANSWER: Exercise programmes designed to prevent falls in older
adults seem also to prevent injuries caused by falls, including the most severe
injuries. Such programmes also reduce the rate of falls leading to medical care.
PMID- 26429909
TI - Molecular Mechanisms and Kinetic Effects of FXYD1 and Phosphomimetic Mutants on
Purified Human Na,K-ATPase.
AB - Phospholemman (FXYD1) is a single-transmembrane protein regulator of Na,K-ATPase,
expressed strongly in heart, skeletal muscle, and brain and phosphorylated by
protein kinases A and C at Ser-68 and Ser-63, respectively. Binding of FXYD1
reduces Na,K-ATPase activity, and phosphorylation at Ser-68 or Ser-63 relieves
the inhibition. Despite the accumulated information on physiological effects,
whole cell studies provide only limited information on molecular mechanisms. As a
complementary approach, we utilized purified human Na,K-ATPase (alpha1beta1 and
alpha2beta1) reconstituted with FXYD1 or mutants S63E, S68E, and S63E,S68E that
mimic phosphorylation at Ser-63 and Ser-68. Compared with control alpha1beta1,
FXYD1 reduces Vmax and turnover rate and raises K0.5Na. The phosphomimetic
mutants reverse these effects and reduce K0.5Na below control K0.5Na. Effects on
alpha2beta1 are similar but smaller. Experiments in proteoliposomes reconstituted
with alpha1beta1 show analogous effects of FXYD1 on K0.5Na, which are abolished
by phosphomimetic mutants and also by increasing mole fractions of DOPS in the
proteoliposomes. Stopped-flow experiments using the dye RH421 show that FXYD1
slows the conformational transition E2(2K)ATP -> E1(3Na)ATP but does not affect
3NaE1P -> E2P3Na. This regulatory effect is explained simply by molecular
modeling, which indicates that a cytoplasmic helix (residues 60-70) docks between
the alphaN and alphaP domains in the E2 conformation, but docking is weaker in E1
(also for phosphomimetic mutants). Taken together with previous work showing that
FXYD1 also raises binding affinity for the Na(+)-selective site III, these
results provide a rather comprehensive picture of the regulatory mechanism of
FXYD1 that complements the physiological studies.
PMID- 26429910
TI - Concentration-dependent Effects of Nuclear Lamins on Nuclear Size in Xenopus and
Mammalian Cells.
AB - A fundamental question in cell biology concerns the regulation of organelle size.
While nuclear size is exquisitely controlled in different cell types,
inappropriate nuclear enlargement is used to diagnose and stage cancer.
Clarifying the functional significance of nuclear size necessitates an
understanding of the mechanisms and proteins that control nuclear size. One
structural component implicated in the regulation of nuclear morphology is the
nuclear lamina, a meshwork of intermediate lamin filaments that lines the inner
nuclear membrane. However, there has not been a systematic investigation of how
the level and type of lamin expression influences nuclear size, in part due to
difficulties in precisely controlling lamin expression levels in vivo. In this
study, we circumvent this limitation by studying nuclei in Xenopus laevis egg and
embryo extracts, open biochemical systems that allow for precise manipulation of
lamin levels by the addition of recombinant proteins. We find that nuclear growth
and size are sensitive to the levels of nuclear lamins, with low and high
concentrations increasing and decreasing nuclear size, respectively.
Interestingly, each type of lamin that we tested (lamins B1, B2, B3, and A)
similarly affected nuclear size whether added alone or in combination, suggesting
that total lamin concentration, and not lamin type, is more critical to
determining nuclear size. Furthermore, we show that altering lamin levels in
vivo, both in Xenopus embryos and mammalian tissue culture cells, also impacts
nuclear size. These results have implications for normal development and
carcinogenesis where both nuclear size and lamin expression levels change.
PMID- 26429911
TI - Poly(ADP-ribosyl)ation of FOXP3 Protein Mediated by PARP-1 Protein Regulates the
Function of Regulatory T Cells.
AB - Poly(ADP-ribose) polymerase 1 (PARP-1) is an ADP-ribosylating enzyme
participating in diverse cellular functions. The roles of PARP-1 in the immune
system, however, have not been well understood. Here we find that PARP-1
interacts with FOXP3 and induces its poly(ADP-ribosyl)ation. By using PARP-1
inhibitors, we show that reduced poly(ADP-ribosyl)ation of FOXP3 results in not
only FOXP3 stabilization and increased FOXP3 downstream genes but also enhanced
suppressive function of regulatory T cells. Our results suggest that PARP-1
negatively regulates the suppressive function of Treg cells at the
posttranslational level via FOXP3 poly(ADP-ribosyl)ation. This finding has
implications for developing PARP-1 inhibitors as potential agents for the
prevention and treatment of autoimmune diseases.
PMID- 26429912
TI - Structural Basis for Clonal Diversity of the Public T Cell Response to a Dominant
Human Cytomegalovirus Epitope.
AB - Cytomegalovirus (CMV) is a ubiquitous and persistent human pathogen that is kept
in check by CD8(+) cytotoxic T lymphocytes. Individuals expressing the major
histocompatibility complex (MHC) class I molecule HLA-A2 produce cytotoxic T
lymphocytes bearing T cell receptors (TCRs) that recognize the immunodominant CMV
epitope NLVPMVATV (NLV). The NLV-specific T cell repertoire is characterized by a
high prevalence of TCRs that are frequently observed in multiple unrelated
individuals. These public TCRs feature identical, or nearly identical,
complementarity-determining region 3alpha (CDR3alpha) and/or CDR3beta sequences.
The TCRs may express public CDR3alpha motifs alone, public CDR3beta motifs alone,
or dual public CDR3alphabeta motifs. In addition, the same public CDR3alpha motif
may pair with different CDR3beta motifs (and the reverse), giving rise to highly
diverse NLV-specific TCR repertoires. To investigate the structural underpinnings
of this clonal diversity, we determined crystal structures of two public TCRs (C7
and C25) in complex with NLV.HLA-A2. These TCRs utilize completely different
CDR3alpha and CDR3beta motifs that, in addition, can associate with multiple
variable alpha and variable beta regions in NLV-specific T cell repertoires. The
C7.NLV.HLA-A2 and C25.NLV.HLA-A2 complexes exhibit divergent TCR footprints on
peptide-MHC such that C25 is more focused on the central portion of the NLV
peptide than is C7. These structures combined with molecular modeling show how
the public CDR3alpha motif of C25 may associate with different variable alpha
regions and how the public CDR3alpha motif of C7 may pair with different CDR3beta
motifs. This interchangeability of TCR V regions and CDR3 motifs permits multiple
structural solutions to binding an identical peptide-MHC ligand and thereby the
generation of a clonally diverse public T cell response to CMV.
PMID- 26429913
TI - Essential Role of the EF-hand Domain in Targeting Sperm Phospholipase Czeta to
Membrane Phosphatidylinositol 4,5-Bisphosphate (PIP2).
AB - Sperm-specific phospholipase C-zeta (PLCzeta) is widely considered to be the
physiological stimulus that triggers intracellular Ca(2+) oscillations and egg
activation during mammalian fertilization. Although PLCzeta is structurally
similar to PLCdelta1, it lacks a pleckstrin homology domain, and it remains
unclear how PLCzeta targets its phosphatidylinositol 4,5-bisphosphate (PIP2)
membrane substrate. Recently, the PLCdelta1 EF-hand domain was shown to bind to
anionic phospholipids through a number of cationic residues, suggesting a
potential mechanism for how PLCs might interact with their target membranes.
Those critical cationic EF-hand residues in PLCdelta1 are notably conserved in
PLCzeta. We investigated the potential role of these conserved cationic residues
in PLCzeta by generating a series of mutants that sequentially neutralized three
positively charged residues (Lys-49, Lys-53, and Arg-57) within the mouse PLCzeta
EF-hand domain. Microinjection of the PLCzeta EF-hand mutants into mouse eggs
enabled their Ca(2+) oscillation inducing activities to be compared with wild
type PLCzeta. Furthermore, the mutant proteins were purified, and the in vitro
PIP2 hydrolysis and binding properties were monitored. Our analysis suggests that
PLCzeta binds significantly to PIP2, but not to phosphatidic acid or
phosphatidylserine, and that sequential reduction of the net positive charge
within the first EF-hand domain of PLCzeta significantly alters in vivo Ca(2+)
oscillation inducing activity and in vitro interaction with PIP2 without
affecting its Ca(2+) sensitivity. Our findings are consistent with theoretical
predictions provided by a mathematical model that links oocyte Ca(2+) frequency
and the binding ability of different PLCzeta mutants to PIP2. Moreover, a PLCzeta
mutant with mutations in the cationic residues within the first EF-hand domain
and the XY linker region dramatically reduces the binding of PLCzeta to PIP2,
leading to complete abolishment of its Ca(2+) oscillation inducing activity.
PMID- 26429914
TI - Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth
Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase
(JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain
Tumor Cells.
AB - Under normal physiologic conditions, the glutathione S-transferase P1 (GSTP1)
protein exists intracellularly as a dimer in reversible equilibrium with its
monomeric subunits. In the latter form, GSTP1 binds to the mitogen-activated
protein kinase, JNK, and inhibits JNK downstream signaling. In tumor cells, which
frequently are characterized by constitutively high GSTP1 expression, GSTP1
undergoes phosphorylation by epidermal growth factor receptor (EGFR) at tyrosine
residues 3, 7, and 198. Here we report on the effect of this EGFR-dependent GSTP1
tyrosine phosphorylation on the interaction of GSTP1 with JNK, on the regulation
of JNK downstream signaling by GSTP1, and on tumor cell survival. Using in vitro
and in vivo growing human brain tumors, we show that tyrosine phosphorylation
shifts the GSTP1 dimer-monomer equilibrium to the monomeric state and facilitates
the formation of the GSTP1-JNK complex, in which JNK is functionally inhibited.
Targeted mutagenesis and functional analysis demonstrated that the increased
GSTP1 binding to JNK results from phosphorylation of the GSTP1 C-terminal Tyr-198
by EGFR and is associated with a >2.5-fold decrease in JNK downstream signaling
and a significant suppression of both spontaneous and drug-induced apoptosis in
the tumor cells. The findings define a novel mechanism of regulatory control of
JNK signaling that is mediated by the EGFR/GSTP1 cross-talk and provides a
survival advantage for tumors with activated EGFR and high GSTP1 expression. The
results lay the foundation for a novel strategy of dual EGFR/GSTP1 for treating
EGFR+ve, GSTP1 expressing GBMs.
PMID- 26429915
TI - Alteration/Deficiency in Activation 3 (ADA3) Protein, a Cell Cycle Regulator,
Associates with the Centromere through CENP-B and Regulates Chromosome
Segregation.
AB - ADA3 (alteration/deficiency in activation 3) is a conserved component of several
transcriptional co-activator and histone acetyltransferase (HAT) complexes.
Recently, we generated Ada3 knock-out mice and demonstrated that deletion of Ada3
leads to early embryonic lethality. The use of Ada3(FL/FL) mouse embryonic
fibroblasts with deletion of Ada3 using adenovirus Cre showed a critical role of
ADA3 in cell cycle progression through mitosis. Here, we demonstrate an
association of ADA3 with the higher order repeat region of the alpha-satellite
region on human X chromosome centromeres that is consistent with its role in
mitosis. Given the role of centromere proteins (CENPs) in mitosis, we next
analyzed whether ADA3 associates with the centromere through CENPs. Both an in
vivo proximity ligation assay and immunofluorescence studies confirmed the
association of ADA3 with CENP-B protein, a highly conserved centromeric protein
that binds to the 17-bp DNA sequences on alpha-satellite DNA. Deletional analysis
showed that ADA3 directly associates with CENP-B through its N terminus, and a
CENP-B binding-deficient mutant of ADA3 was incompetent in cell proliferation
rescue. Notably, knockdown of ADA3 decreased binding of CENP-B onto the
centromeres, suggesting that ADA3 is required for the loading of CENP-B onto the
centromeres. Finally, we show that deletion of Ada3 from Ada3(FL/FL) mouse
embryonic fibroblasts exhibited various chromosome segregation defects. Taken
together, we demonstrate a novel ADA3 interaction with CENP-B-centromere that may
account for its previously known function in mitosis. This study, together with
its known function in maintaining genomic stability and its mislocalization in
cancers, suggests an important role of ADA3 in mitosis.
PMID- 26429916
TI - Interaction of Heat Shock Protein Cpn10 with the Cyclin E/Cdk2 Substrate Nuclear
Protein Ataxia-Telangiectasia (NPAT) Is Involved in Regulating Histone
Transcription.
AB - Precise modulation of histone gene transcription is critical for cell cycle
progression. As a direct substrate of Cyclin E/CDK2, nuclear protein ataxia
telangiectasia (NPAT) is a crucial factor in regulating histone transcription and
cell cycle progression. Here we identified that Cpn10/HSPE, a 10-kDa heat shock
protein, is a novel interacting partner of NPAT. A pool of Cpn10 is colocalized
with NPAT foci during G1 and S phases in nuclei. Gain- and loss-of-function
experiments unraveled an essential role of Cpn10 in histone transcription. A
conserved DLFD motif within Cpn10 was critical for targeting NPAT and modulating
histone transcription. More importantly, knockdown of Cpn10 disrupted the focus
formation of both NPAT and FADD-like interleukin-1beta-converting enzyme
associated huge protein without affecting Coilin-positive Cajal bodies. Finally,
Cpn10 is important for S phase progression and cell proliferation. Taken
together, our finding revealed a novel role of Cpn10 in the spatial regulation of
NPAT signaling and disclosed a previously unappreciated link between the heat
shock protein and histone transcription regulation.
PMID- 26429917
TI - Syk Is Recruited to Stress Granules and Promotes Their Clearance through
Autophagy.
AB - Syk is a cytoplasmic kinase that serves multiple functions within the immune
system to couple receptors for antigens and antigen-antibody complexes to
adaptive and innate immune responses. Recent studies have identified additional
roles for the kinase in cancer cells, where its expression can either promote or
suppress tumor cell growth, depending on the context. Proteomic analyses of Syk
binding proteins identified several interacting partners also found to be
recruited to stress granules. We show here that the treatment of cells with
inducers of stress granule formation leads to the recruitment of Syk to these
protein-RNA complexes. This recruitment requires the phosphorylation of Syk on
tyrosine and results in the phosphorylation of proteins at or near the stress
granule. Grb7 is identified as a Syk-binding protein involved in the recruitment
of Syk to the stress granule. This recruitment promotes the formation of
autophagosomes and the clearance of stress granules from the cell once the stress
is relieved, enhancing the ability of cells to survive the stress stimulus.
PMID- 26429919
TI - You're Not Big--You're Just Tall, That's All!
PMID- 26429918
TI - Long-term effects of pegvisomant on comorbidities in patients with acromegaly: a
retrospective single-center study.
AB - CONTEXT: The effect of pegvisomant on IGF1 levels in patients with acromegaly is
well documented, but little is known of its long-term impact on comorbidity. AIM:
The aim of this retrospective study was to evaluate the effects of long-term
pegvisomant therapy on cardiorespiratory and metabolic comorbidity in patients
with acromegaly. PATIENTS AND METHODS: We analyzed the long-term (up to 10 years)
effect of pegvisomant therapy given alone (n=19, 45%) or in addition to
somatostatin analogues and/or cabergoline (n=23, 55%) on echocardiographic,
polysomnographic and metabolic parameters in respectively 42, 12 and 26 patients
with acromegaly followed in Bicetre hospital. RESULTS: At the first cardiac
evaluation, 20+/-16 months after pegvisomant introduction, IGF1 levels normalized
in 29 (69%) of the 42 patients. The left ventricular ejection fraction (LVEF)
improved significantly in patients whose basal LVEF was <=60% and decreased in
those whose LVEF was >70%. The left ventricular mass index (LVMi) decreased from
123+/-25 to 101+/-21 g/m(2) (P<0.05) in the 17 patients with a basal LVMi higher
than the median (91 g/m(2)), while it remained stable in the other patients.
Pegvisomant reduced the apnoea-hypopnea index and cured obstructive sleep apnea
(OSA) in four of the eight patients concerned. Long-term follow-up of 22 patients
showed continuing improvements in cardiac parameters. The BMI and LDL cholesterol
level increased minimally during pegvisomant therapy, and other lipid parameters
were not modified. CONCLUSIONS: Long-term pegvisomant therapy not only normalizes
IGF1 in a large proportion of patients but also improves cardiac and respiratory
comorbidity.
PMID- 26429920
TI - Association of Height with Elevated Mortality Risk in ESRD: Variation by Race and
Gender.
AB - The association of adult height with mortality has been extensively investigated
in the general population, but little is known about this relationship among
dialysis patients. We explored the relationship between height and mortality in a
retrospective cohort study of 1,171,842 adults who began dialysis in the United
States from 1995 to 2008 and were followed until December 31, 2010. We evaluated
height-mortality associations in sex-specific quintiles of increasing height (Q1
Q5) using multivariable Cox regression models adjusted for demographics, comorbid
conditions, lifestyle and disability indicators, socioeconomic status, and body
weight. For men, compared with the referent quintile (Q1 <167 cm), successive
height quintiles had significantly increased hazard ratios (HRs [95% confidence
interval]) for mortality: 1.04 (1.02-1.06), 1.08 (1.06-1.10), 1.12 (1.11-1.14),
and 1.18 (1.16-1.20) for Q2-Q5, respectively. For women (referent Q1 <155 cm),
HRs for mortality were 1.00 (0.99-1.02), 1.05 (1.03-1.06), 1.05 (1.03-1.07), and
1.08 (1.06-1.10) for Q2-Q5, respectively. However, stratification by race showed
the pattern of association differed significantly by race (P<0.001 for
interaction). For black men, unlike other race groups, height only associated
with mortality in Q5, with an HR of 1.06 (1.02-1.09). For black women, HRs for
mortality were 0.94 (0.91-0.97), 0.98 (0.95-1.02), 0.96 (0.93-0.99), and 0.99
(0.96-1.02) for Q2-Q5, respectively. These results indicate tallness is
associated with higher mortality risks for adults starting dialysis, but this
association did not extend to black patients.
PMID- 26429921
TI - Three-dimensional echocardiography vs. computed tomography for transcatheter
aortic valve replacement sizing.
AB - AIMS: The accuracy of transcatheter aortic valve replacement (TAVR) sizing using
three-dimensional transoesophageal echocardiography (3D-TEE) compared with the
gold-standard multi-slice computed tomography (MSCT) remains unclear. We compare
aortic annulus measurements assessed using these two imaging modalities. METHODS
AND RESULTS: We performed a single-centre prospective cohort study, including 53
consecutive patients undergoing TAVR, who had both MSCT and 3D-TEE for aortic
annulus sizing. Aortic annular dimensions, expected transcatheter heart valve
(THV) oversizing, and hypothetical valve size selection based on CT and TEE were
compared. 3D-TEE and CT cross-sectional mean diameter (r = 0.69), perimeter (r =
0.70), and area (r = 0.67) were moderately to highly correlated (all P-values
<0.0001). 3D-TEE-derived measurements were significantly smaller compared with
MSCT: perimeter (68.6 +/- 5.9 vs. 75.1 +/- 5.7 mm, respectively; P < 0.0001);
area (345.6 +/- 64.5 vs. 426.9 +/- 68.9 mm(2), respectively; P < 0.0001). The
percentage difference between 3D-TEE and MSCT measurements was around 9%.
Agreement between MSCT- and 3D-TEE-based THV sizing (perimeter) occurred in 44%
of patients. Using the 3D-TEE perimeter annular measurements, up to 50% of
patients would have received an inappropriate valve size according to
manufacturer-recommended, area-derived sizing algorithms. CONCLUSION: Aortic
annulus measurements for pre-procedural TAVR assessment by 3D-TEE are
significantly smaller than MSCT. In this study, such discrepancy would have
resulted in up to 50% of all patients receiving the wrong THV size. 3D-TEE should
be used for TAVR sizing, only when MSCT is not available or contraindicated. The
clinical impact of this information requires further study.
PMID- 26429923
TI - Sexual Selection of Protamine 1 in Mammals.
AB - Protamines have a crucial role in male fertility. They are involved in sperm
chromatin packaging and influence the shape of the sperm head and, hence, are
important for sperm performance. Protamine structure is basic with numerous
arginine-rich DNA-binding domains. Postcopulatory sexual selection is thought to
play an important role in protamine sequence evolution and expression. Here, we
analyze patterns of evolution and sexual selection (in the form of sperm
competition) acting on protamine 1 gene sequence in 237 mammalian species. We
assessed common patterns as well as differences between the major mammalian
subclasses (Eutheria, Metatheria) and clades. We found that a high arginine
content in protamine 1 associates with a lower sperm head width, which may have
an impact on sperm swimming velocity. Increase in arginine content in protamine 1
across mammals appears to take place in a way consistent with sexual selection.
In metatherians, increase in sequence length correlates with sexual selection.
Differences in selective pressures on sequences and codon sites were observed
between mammalian clades. Our study revealed a complex evolutionary pattern of
protamine 1, with different selective constraints, and effects of sexual
selection, between mammalian groups. In contrast, the effect of arginine content
on head shape, and the possible involvement of sperm competition, was identified
across all mammals.
PMID- 26429922
TI - Evolution of DNA-Binding Sites of a Floral Master Regulatory Transcription
Factor.
AB - Flower development is controlled by the action of key regulatory transcription
factors of the MADS-domain family. The function of these factors appears to be
highly conserved among species based on mutant phenotypes. However, the
conservation of their downstream processes is much less well understood, mostly
because the evolutionary turnover and variation of their DNA-binding sites (BSs)
among plant species have not yet been experimentally determined. Here, we
performed comparative ChIP (chromatin immunoprecipitation)-seq experiments of the
MADS-domain transcription factor SEPALLATA3 (SEP3) in two closely related
Arabidopsis species: Arabidopsis thaliana and A. lyrata which have very similar
floral organ morphology. We found that BS conservation is associated with DNA
sequence conservation, the presence of the CArG-box BS motif and on the relative
position of the BS to its potential target gene. Differences in genome size and
structure can explain that SEP3 BSs in A. lyrata can be located more distantly to
their potential target genes than their counterparts in A. thaliana. In A.
lyrata, we identified transposition as a mechanism to generate novel SEP3 binding
locations in the genome. Comparative gene expression analysis shows that the
loss/gain of BSs is associated with a change in gene expression. In summary, this
study investigates the evolutionary dynamics of DNA BSs of a floral key
regulatory transcription factor and explores factors affecting this phenomenon.
PMID- 26429924
TI - Evidence for neurotoxicity associated with amoxicillin in juvenile rats.
AB - Amoxicillin (AMX) is one of the most commonly prescribed antibiotics for
children, and childhood is the period to have the highest risk for toxicity cases
including drug-induced adverse reactions. Some neurological adverse effects
(anxiety, hyperactivity, confusion, convulsions, and behavioral changes) have
been reported related to AMX treatment. In the present study, we aimed to
determine the neurotoxic effects of AMX administration at clinically relevant
doses in female juvenile rats. AMX was administered in single oral daily doses of
25 and 50 mg/kg for 14 days. According to our results, while AMX administration
caused a significant increase in the immobility time of animals, swimming time of
these animals significantly decreased. AMX administration significantly reduced
the onset of pentylenetetrazole-induced convulsions. The serotonin levels of
brain tissues in the AMX-administered groups were decreased significantly, which
is thought to be related to depression. The glutamate levels in brain tissues
increased significantly in AMX-administered groups, which is thought to be
related to convulsion. Otherwise, superoxide dismutase and catalase activities
were significantly decreased in brain tissues of AMX-administered groups. In
conclusion, AMX administration triggered depression and shortened the time of the
appearance of first seizure in juvenile rats. Also, altered brain
neurotransmitter levels and increased oxidative stress observed in our study were
thought to be the possible underlying mechanisms of AMX-induced neurotoxicity.
PMID- 26429925
TI - Does rosmarinic acid treatment have protective role against sepsis-induced
oxidative damage in Wistar Albino rats?
AB - Reactive oxygen species are believed to be involved in the development of sepsis.
Plant-derived phenolic compounds are thought to be possible therapeutic agents
against sepsis because of their antioxidant properties. Rosmarinic acid (RA) is a
phenolic compound commonly found in various plants, which has many biological
activities including antioxidant activity. The aim of this study was to
investigate the effects of RA on sepsis-induced DNA damage in the lymphocytes and
liver and kidney cells of Wistar albino rats by alkaline comet assay with and
without formamidopyrimidine DNA glycosylase protein. The oxidative stress
parameters such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
activities and total glutathione (GSH) and malondialdehyde (MDA) levels in the
liver and kidney tissues and an inflammatory cytokine, tumor necrosis factor
alpha (TNF-alpha) level in plasma were also evaluated. It is found that DNA
damage in the lymphocytes, livers, and kidneys of the RA-treated rats was
significantly lower than that in the sepsis-induced rats. RA treatment also
decreased the MDA levels and increased the GSH levels and SOD and GSH-Px
activities in the livers and kidneys of the sepsis-induced rats. Plasma TNF-alpha
level was found to be decreased in the RA-treated rats. It seems that RA might
have a role in the attenuation of sepsis-induced oxidative damage not only by
decreasing the DNA damage but also by increasing the antioxidant status and DNA
repair capacity of the animals.
PMID- 26429926
TI - Bcl-2 and Fas expression in peripheral blood leukocytes of patients with
alcoholic and autoimmune liver disorders.
AB - BACKGROUND: This article is devoted to the inquiry of three diseases of the
liver: alcoholic liver disease (ALD), primary biliary cirrhosis (PBC), and
autoimmune hepatitis (AIH). The aim of the study was to assess the changes in
populations of circulating lymphocytes expressing antiapoptotic bcl-2 molecule
and proapoptotic Fas (cluster of differentiation 95(CD95)) receptor in patients
with ALD, AIH, and PBC. MATERIALS AND METHODS: The study population consisted of
110 patients with ALD (n = 50), PBC (n = 30), and AIH (n = 30) and age-matched
healthy volunteers (n = 25). Peripheral blood lymphocytes were isolated, stained
with monoclonal antibodies against CD4, CD8, and CD19 antigen; intracellular bcl
2; and surface Fas receptor (CD95) antigens, and estimated using the flow
cytometric method. RESULTS: Bcl-2 expression was the highest in CD4+ and CD19+ T
lymphocytes in ALD; however, only the differences in median/mean fluorescence
intensity values of CD4+bcl-2+ lymphocytes between ALD and PBC group and CD19+bcl
2+ between ALD and PBC groups were statistically significant, indicating the
different role of B cells in pathology of ALD and PBC. In contrast to that,
statistically significant higher percentage of CD4+, CD8+, and CD19+ bearing Fas
receptor in all groups of patients with liver diseases in comparison with the
control subjects were estimated. The highest expression of Fas in CD4+
lymphocytes in ALD and in CD8+ cells of PBC and AIH groups were detected.
CONCLUSION: Low expression of bcl-2 molecule and high expression of Fas in
peripheral blood lymphocytes indicate significant dysregulation of apoptotic
mechanisms not only in the liver but also in peripheral blood lymphocytes in all
examined groups, especially in ALD group.
PMID- 26429927
TI - Evaluation of matrix metalloproteinase, myeloperoxidase, and oxidative damage in
mesenteric ischemia-reperfusion injury.
AB - BACKGROUND: In this study, we investigated the alterations of matrix
metalloproteinase (MMP) and tissue inhibitors of metalloproteinases (TIMPs),
acute inflammation, and oxidative damage in the circulatory system and the
intestine in response to mesenteric ischemia/reperfusion (I/R). METHODS: Twenty
one rats were divided randomly into the following three groups (n = 7 in each
group): a sham group (CG), an ischemic group (IG), and an I/R group (I/RG). MMP
9, TIMP-1, and myeloperoxidase (MPO) were measured using the enzyme-linked
immunosorbent assay method, and lipid peroxidation (quantified as thiobarbituric
acid reactive substances (TBARS) content), ischemia-modified albumin, the
prooxidant-antioxidant balance (PAB), and ferric-reducing antioxidant power
(FRAP) were measured spectrophotometrically. The degree of intestinal injury was
evaluated according to the Chiu scoring system. RESULTS: A significant difference
between the mean serum TIMP-1 and MMP-9 levels and the alanine transaminase
activity was found among the groups. Compared with the I/RG group a significant
difference in the mean tissue MMP-9, MPO, and TBARS levels in addition to the PAB
and FRAP was found between the CG and IG groups. The level of MMP-9 also
demonstrated a strong, positive, and valid correlation with the TBA-RS levels. A
significant morphological change was observed in both the IG and the I/RG groups.
The degree of intestinal injury was more severe in the I/R group and was
characterized by either villous denudation or villous loss. CONCLUSIONS: These
results suggest that MMP-9, TIMP-1, MPO, and oxidative stress may be important in
the intestinal injury development that is induced by acute mesenteric I/R in a
rat model. MMP-9 overexpression may increase the extent of intestinal villous
loss, particularly when MMP-9 is upregulated by the TBARS present in the
intestinal injury.
PMID- 26429928
TI - Coadministration of alloxan and nicotinamide in rats produces biochemical changes
in blood and pathological alterations comparable to the changes in type II
diabetes mellitus.
AB - BACKGROUND: In the present study, thirty six male Sprague Dawley rats were
randomly divided into six groups and were injected with varying doses of alloxan
(Ax) and nicotinamide (NA). The serum levels of glucose, insulin, and adiponectin
were measured weekly up to 4 weeks. RESULTS: Elevated levels of glucose were
observed in all groups on days 7, 14, 21, and 28, except in groups a and f
(control). The serum insulin levels were significantly elevated in groups b and c
on day 7, when compared with that in group f, whereas a decrease in the serum
insulin levels was observed in groups d and e on days 21 and 28. The adiponectin
levels showed inconsistencies on days 7 and 14. However, significant decrease in
the adiponectin levels was observed on days 21 and 28. Histological section of
the pancreas showed mild (group a), moderate (group b) to severe (groups c, d,
and e) degenerative changes. Concomitant fatty changes in the liver and
inflammatory infiltration of the kidney were markedly observed in all the treated
groups, when compared to control. CONCLUSION: These results suggested that the
use of selective combination of Ax120 + NA50 injection demonstrated type II
diabetes mellitus in rats.
PMID- 26429929
TI - Combination of paracetamol or ketamine with meperidine enhances antinociception.
AB - OBJECTIVES: Dealing with pain is one of the most important issues of medicine.
All of the studies aim to find a drug or combination of drugs in order to have
more effective analgesia and less side effects. In this study, we aimed to
investigate the antinociceptive effects of combination of paracetamol or ketamine
with meperidine. METHODS: In this study, we evaluated the systemic
antinociceptive effects of meperidine, paracetamol, and ketamine one by one with
their combinations. We used 50 mice (weighing 25-30 g), which were divided into 5
groups with each group consisting of 10 mice. Meperidine was applied to animals
with increasing doses and their tail flick latencies (TFL) were noted at 20, 40,
60, 90, 120, 180, and 240 min. The same protocol was repeated after the
combination of meperidine with paracetamol or ketamine. RESULTS: There was no
analgesic effect on low doses of ketamine and paracetamol at TFL measurements.
But the combination of low doses of these drugs with meperidine significantly
increased TFL (p < 0.05). CONCLUSION: It was observed that meperidine + ketamine
and meperidine + paracetamol combinations have potent analgesic effect.
PMID- 26429930
TI - The compromise of dynamic disulfide/thiol homeostasis as a biomarker of oxidative
stress in trichloroethylene exposure.
AB - In this study, we aimed to investigate disulfide/thiol homeostasis in
trichloroethylene (TCE) exposure. The study was carried out in 30 nonsmoker TCE
exposed workers with a variety of occupations. Additionally, 30 healthy nonsmoker
volunteers were recruited as the control group. TCE exposure was determined by
measuring urinary trichloroacetic acid (TCA) concentration. Median urinary TCA
levels of exposed workers (20.5 mg/L) were significantly higher than control
subjects (5 mg/L). Thiol and disulfide concentrations were determined using a
novel automated method. Disulfide/thiol ratio was significantly higher in the
exposed group (p < 0.001). Thiol/disulfide homeostasis was found to be disturbed
in TCE-exposed workers. We predict that in TCE-exposed workers this disturbance
can be a therapeutic target, and the efficiency of the treatment can easily be
monitored by the novel method we used.
PMID- 26429931
TI - Biocompatibility evaluation of orthodontic composite by real-time cell analysis.
AB - INTRODUCTION: The aim of this study was to evaluate the cytotoxic effects of
three different light-cured orthodontic composites. MATERIAL AND METHODS: Light
Bond (Reliance orthodontic products), Grengloo (Ormco corporation), and Kurasper
F (Kuraray Europe GmbH) were selected for the experiment. Specimens were prepared
according to the manufacturers' instructions, measuring 5 mm in diameter and 2 mm
in thickness. Fibroblast cells were obtained from healthy gingival connective
tissues. The composite cylinders were incubated in Dulbecco's modified Eagle's
culture medium for 72 h according to ISO 10993-5 standards. The xCELLigence
method was used to evaluate fibroblast cell vitality. After seeding 200 mL of the
cell suspensions into the wells (20,000 cells/well) of the E-plate 96, gingival
fibroblasts were treated with bioactive components released by the orthodontic
composite materials and monitored every 15 min for 121 h. RESULTS: There were no
significant differences between the human gingival fibroblast (HGF) cell indexes
of the control and all testing groups (p > 0.05) at 24 and 48 h. Light Bond
demonstrated statistically significant decrease in HGF index (p < 0.05) at 72 h,
but there was no significant difference among the Kurasper F, Grengloo, and
untreated control groups (p > 0.05). Light Bond (p < 0.001) and Grengloo (p <
0.05) groups had lower HGF cell index values when compared to untreated control
group, but Kurasper F demonstrated no significant differences between the control
groups at 96 h (p > 0.05). CONCLUSION: Orthodontic composite materials include
biologically active components and may change oral tissue. So, biocompatible
orthodontic bonding composites should be used.
PMID- 26429932
TI - Differential effects of grape juice on gastric emptying and renal function from
cisplatin-induced acute adverse toxicity.
AB - Grape skin and seeds contain large amounts of phytochemicals such as polyphenols,
resveratrol, and proanthocyanidins, which possess antioxidant activities.
Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have
also been known to produce acute adverse effects. The aim of this study was to
investigate the protective effects of antioxidant properties of whole grape juice
(with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders
and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in
whole grape juice-pretreated rats when compared to cisplatin treatment alone. The
expression of ghrelin mRNA of stomach is increased in rats with whole grape
juice. However, pretreatment with whole grape juice did not reduce renal function
markers in acute renal toxicity. No significant changes were recorded in the
oxidative stress/antioxidant status parameters of any study group. In contrast,
pretreatment with whole grape juice slightly improved tubular cell vacuolization,
tubular dilatation, and cast formation in renal tubules. These results show that
consumption of whole grape juice induces somewhat beneficial effects in
preventing cisplatin-mediated dyspepsia but does not offer protection against
cisplatin-induced acute renal toxicity.
PMID- 26429935
TI - "PEAR-ing" Genomic and Epigenomic Analyses for Cancer Gene Discovery.
AB - Somatic structural variants in tumor genomes can deregulate transcription through
repositioning of enhancer elements. A new method, PEAR-ChIP, leverages paired-end
H3K27ac chromatin immunoprecipitation combined with high-throughput sequencing
and current computational methods to identify such events.
PMID- 26429936
TI - T Regulatory Cells Gone Bad: An Oncogenic Immune Response against Enterotoxigenic
B. fragilis Infection Leads to Colon Cancer.
AB - T regulatory cells trigger an oncogenic immune response against enterotoxigenic
B. fragilis infection. The implications of an overall shift in the colonic
homeostasis are discussed.
PMID- 26429937
TI - Rational Engineering Defines a Molecular Switch That Is Essential for Activity of
Spider-Venom Peptides against the Analgesics Target NaV1.7.
AB - Many spider-venom peptides are known to modulate the activity of the voltage
gated sodium (NaV) subtype 1.7 (NaV1.7) channel, which has emerged as a promising
analgesic target. In particular, a class of spider-venom peptides (NaSpTx1) has
been found to potently inhibit NaV1.7 (nanomolar IC50), and has been shown to
produce analgesic effects in animals. However, one member of this family [u-TRTX
Hhn2b (Hhn2b)] does not inhibit mammalian NaV channels expressed in dorsal root
ganglia at concentrations up to 100 uM. This peptide is classified as a NaSpTx1
member by virtue of its cysteine spacing and sequence conservation over
functionally important residues. Here, we have performed detailed structural and
functional analyses of Hhn2b, leading us to identify two nonpharmacophore
residues that contribute to human NaV1.7 (hNaV1.7) inhibition by nonoverlapping
mechanisms. These findings allowed us to produce a double mutant of Hhn2b that
shows nanomolar inhibition of hNaV1.7. Traditional structure/function analysis
did not provide sufficient resolution to identify the mechanism underlying the
observed gain of function. However, by solving the high-resolution structure of
both the wild-type and mutant peptides using advanced multidimensional NMR
experiments, we were able to uncover a previously unknown network of interactions
that stabilize the pharmacophore region of this class of venom peptides. We
further monitored the lipid binding properties of the peptides and identified
that one of the key amino acid substitutions also selectively modulates the
binding of the peptide to anionic lipids. These results will further aid the
development of peptide-based analgesics for the treatment of chronic pain.
PMID- 26429938
TI - An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1
Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression.
AB - The Na(+)/glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in
intestinal epithelial cells. It has been shown that the intestinal SGLT1 level is
significantly increased in diabetic individuals and positively correlated with
the pathogenesis of diabetes. The development of targeted therapeutics that can
reduce the intestinal SGLT1 expression level is, therefore, important. In this
study, we showed that ginsenoside Rg1 effectively decreased intestinal glucose
uptake through inhibition of SGLT1 gene expression in vivo and in vitro.
Transient transfection analysis of the SGLT1 promoter revealed an essential cAMP
response element (CRE) that confers the Rg1-mediated inhibition of SGLT1 gene
expression. Chromatin immunoprecipitation assay and targeted CRE-binding protein
(CREB) silencing demonstrated that Rg1 reduced the promoter binding of CREB and
CREB binding protein associated with an inactivated chromatin status. In
addition, further studies showed that the epidermal growth factor receptor (EGFR)
signaling pathway also plays an essential role in the inhibitory effect of Rg1;
taken together, our study demonstrates the involvement of the EGFR-CREB signaling
pathway in the Rg1-mediated downregulation of SGLT1 expression, which offers a
potential strategy in the development of antihyperglycemic and antidiabetic
treatments.
PMID- 26429939
TI - Nicotine Dependence Reveals Distinct Responses from Neurons and Their Resident
Nicotinic Receptors in Medial Habenula.
AB - Nicotinic acetylcholine receptors (nAChRs) are the molecular target of nicotine.
nAChRs in the medial habenula (MHb) have recently been shown to play a role in
nicotine dependence, but it is not clear which nAChR subtypes or MHb neuron types
are most important. To identify MHb nAChRs and/or cell types that play a role in
nicotine dependence, we studied these receptors and cells with brain slice
electrophysiology using both acute and chronic nicotine application. Cells in the
ventroinferior (MHbVI) and ventrolateral MHb (MHbVL) subregions expressed
functional nAChRs with different pharmacology. Further, application of nicotine
to cells in these subregions led to different action potential firing patterns.
The latter result was correlated with a differing ability of nicotine to induce
nAChR desensitization. Chronic nicotine caused functional upregulation of nAChRs
selectively in MHbVI cells, but did not change nAChR function in MHbVL.
Importantly, firing responses were also differentially altered in these
subregions following chronic nicotine. MHbVI neurons treated chronically with
nicotine exhibited enhanced basal pacemaker firing but a blunted nicotine-induced
firing response. MHbVL neurons did not change their firing properties in response
to chronic nicotine. Together, these results suggest that acute and chronic
nicotine differentially affect nAChR function and output of cells in MHb
subregions. Because the MHb extensively innervates the interpeduncular nucleus,
an area critical for both affective and somatic signs of withdrawal, these
results could reflect some of the neurophysiological changes thought to occur in
the MHb to the interpeduncular nucleus circuit in human smokers.
PMID- 26429940
TI - The influence of blood storage time and general anaesthesia on chromosomal
radiosensitivity assessment.
AB - The micronucleus assay (MN assay) is a well-established assay in genetic
toxicology, biomonitoring of mutagen-exposed populations and chromosomal
radiosensitivity testing. To evaluate the effect of storage time on the
chromosomal radiosensitivity assessment in lymphocytes, micronuclei (MN) yields
in blood samples received and processed on the same day were compared with MN
yields obtained when blood cultures were set up 24 and 48h after blood sampling.
Furthermore, the influence of general anaesthesia on MN and binucleated cells
(BN) yields in the MN assay was considered. Blood samples of 10 healthy donors
were irradiated and blood cultures were set up during the same day of blood
sampling or with a delay of 24 or 48h. The MN assay was also performed on two
blood samples from 60 women undergoing breast surgery. The first blood sample was
taken before general anaesthesia and the second sample, 2h after anaesthesia
induction. Fifty percent of the blood samples were transported to the
cytogenetics lab within 2h while the other 50% reached the lab after 24h. The
results of this study show a decrease in BN and an increase in MN yields with
increasing storage time before irradiation and setting up of the MN assay for
both healthy controls and patients. The administration of general anaesthesia in
patients resulted in lower BN yields, higher spontaneous MN yields but no
differences in radiation-induced MN yields. In conclusion, this study indicates
that the time between blood sampling and the in vitro irradiation of the samples
for the MN assay influences the MN yields. Delays of more than 24h should be
avoided. To assess chromosomal radiosensitivity in patients, blood samples should
be taken before induction of general anaesthesia as anaesthesia can have an
impact on the reliability of the MN results.
PMID- 26429941
TI - Egg consumption and incident type 2 diabetes: are there any advantages to
excessive consumption of eggs?
PMID- 26429942
TI - Reply to T Kawada.
PMID- 26429943
TI - Is this the end of (-)-epicatechin, or not? New study highlights the complex
challenges associated with research into the cardiovascular health benefits of
bioactive food constituents.
PMID- 26429944
TI - Reply to H Schroeter et al.
PMID- 26429945
TI - Sales response to price promotions in Great Britain: effect size 1/100 of that
claimed.
PMID- 26429947
TI - Erratum for Nakamura et al. Price promotions on healthier compared with less
healthy foods: a hierarchical regression analysis of the impact on sales and
social patterning of responses to promotions in Great Britain. Am J Clin Nutr
2015;101:808-16.
PMID- 26429946
TI - Reply to MD Chatfield.
PMID- 26429948
TI - Erratum for Kim et al. Effects of egg consumption on carotenoid absorption from
co-consumed, raw vegetables. Am J Clin Nutr 2015;102:75-83.
PMID- 26429949
TI - Erratum for Adebamowo et al. Association between intakes of magnesium, potassium,
and calcium and risk of stroke: 2 cohorts of US women and updated meta-analyses.
Am J Clin Nutr 2015;101:1269-77.
PMID- 26429951
TI - Global research productivity of N-acetylcysteine use in paracetamol overdose: A
bibliometric analysis (1976-2012).
AB - PURPOSE: The main objective of this study was to examine the publication pattern
of N-acetylcysteine (NAC) research output for paracetamol overdose at the global
level. METHODS: Data were searched for documents that contained specific words
regarding NAC and paracetamol as keywords in the title and/or abstract and/or
keywords. Scientific output was evaluated based on a methodology developed and
used in other bibliometric studies. Research productivity was adjusted to the
national population and nominal gross domestic product per capita. RESULTS: The
criteria were met by 367 publications from 33 countries. The highest number of
articles associated with the use of NAC in paracetamol overdose was from the
United States of America (USA; 39.78%), followed by the United Kingdom (UK;
11.99%). After adjusting for economy and population power, USA (2.822), Iran
(1.784) and UK (1.125) had the highest research productivity. The total number of
citations at the time of data analysis (14 March 2014) was 8785 with an average
of 23.9 citations per document and a median (interquartile range) of 6 (1-22).
The h-index of the retrieved documents was 48. The highest h-index was 32 for
USA, followed by 20 for UK. Furthermore, the highest number of collaborations
with international authors for each country was held by USA with 11 countries,
followed by Canada with 7 countries. CONCLUSION: The amount of NAC-based research
activity was low in some countries, and more effort is needed to bridge this gap
and to promote better evaluation of NAC use worldwide. Our findings demonstrate
that NAC use for paracetamol overdose remains a hot issue in scientific research
and may have a larger audience compared with other toxicological aspects. Editors
and authors in the field of toxicology might usefully promote the submission of
work on NAC in future to improve their journal's impact.
PMID- 26429952
TI - Roundtable on the Future of Nuclear Medicine Training.
PMID- 26429953
TI - uPAR as a Glioma Imaging Target.
PMID- 26429954
TI - Reply: Roundtable on the Future of Nuclear Medicine Training.
PMID- 26429955
TI - Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in
Glioblastoma.
AB - Glioblastoma is one of the most malignant types of human cancer, and the
prognosis is poor. The development and validation of novel molecular imaging
biomarkers has the potential to improve tumor detection, grading, risk
stratification, and treatment monitoring of gliomas. The aim of this study was to
explore the potential of PET imaging of the urokinase-type plasminogen activator
receptor (uPAR) in glioblastoma. METHODS: The uPAR messenger RNA expression of
tumors from 19 glioblastoma patients was analyzed, and a cell culture derived
from one of these patients was used to establish an orthotopic xenograft model of
glioblastoma. Tumor growth was monitored using bioluminescence imaging. Five to
six weeks after inoculation, all mice were scanned with small-animal PET/CT using
two new uPAR PET ligands ((64)Cu-NOTA-AE105 and (68)Ga-NOTA-AE105) and, for
comparison, O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET). One MRI scan was
obtained for each mouse to confirm tumor location. The uPAR specificity of (64)Cu
NOTA-AE105 was confirmed by alignment of hematoxylin- and eosin-stained and uPAR
immunohistochemistry-stained slides of the brain with the activity distribution
as determined using autoradiography. RESULTS: uPAR expression was found in all 19
glioblastoma patient tumors, and high expression of uPAR correlated with
decreased overall survival (P = 0.04). Radiolabeling of NOTA-AE105 with (64)Cu
and (68)Ga was straightforward, resulting in a specific activity of approximately
20 GBq/MUmol and a radiochemical purity of more than 98% for (64)Cu-NOTA-AE105
and more than 97% for (68)Ga-NOTA-AE105. High image contrast resulting in clear
tumor delineation was found for both (68)Ga-NOTA-AE105 and (64)Cu-NOTA-AE105.
Absolute uptake in tumor was higher for (18)F-FET (3.5 +/- 0.8 percentage
injected dose [%ID]/g) than for (64)Cu-NOTA-AE105 (1.2 +/- 0.4 %ID/g) or (68)Ga
NOTA-AE105 (0.4 +/- 0.1 %ID/g). A similar pattern was observed in background
brain tissue, where uptake was 1.9 +/- 0.1 %ID/g for (18)F-fluorothymidine,
compared with 0.05 +/- 0.01 %ID/g for (68)Ga-NOTA-AE105 and 0.11 +/- 0.02 %ID/g
for (64)Cu-NOTA-AE105. The result was a significantly higher tumor-to-background
ratio for both (68)Ga-NOTA-AE105 (7.6 +/- 2.1, P < 0.05) and (64)Cu-NOTA-AE105
(10.6 +/- 2.3, P < 0.01) than for (18)F-FET PET (1.8 +/- 0.3). Autoradiography of
brain slides confirmed that the accumulation of (64)Cu-NOTA-AE105 corresponded
well with uPAR-positive cancer cells. CONCLUSION: On the basis of our
translational study, uPAR PET may be a highly promising imaging biomarker for
glioblastoma. Further clinical exploration of uPAR PET in glioblastoma is
therefore justified.
PMID- 26429956
TI - Dose-Finding Quantitative 18F-FDG PET Imaging Study with the Oral Pan-AKT
Inhibitor GSK2141795 in Patients with Gynecologic Malignancies.
AB - AKT (a serine/threonine-specific protein kinase) regulates many cellular
processes contributing to cytotoxic drug resistance. This study's primary
objective examined the relationship between GSK2141795, an oral, pan-AKT
inhibitor, and (18)F-FDG PET markers of glucose metabolism in tumor tissue to
determine whether (18)F-FDG PET could be used to guide personalized dosing of
GSK2141795. Biomarker analysis of biopsies was also undertaken. METHODS: Twelve
patients were enrolled in 3 cohorts; all underwent dynamic (18)F-FDG PET scans
and serial pharmacokinetic sampling at baseline, week 2, and week 4 with tumor
biopsies before treatment and at week 4. Response was evaluated by RECIST v1.1
and Gynecologic Cancer Intergroup criteria. Biopsy samples were analyzed for
mutations and protein expression. RESULTS: GSK2141795 did not significantly
influence blood glucose levels. No dose-response relationship was observed
between GSK2141795 pharmacokinetics and (18)F-FDG PET pharmacodynamic measures;
however, an exposure-response relationship was seen between maximum drug
concentrations and maximal decrease in (18)F-FDG uptake in the best-responding
tumor. This relationship also held for pharmacokinetic parameters of exposure and
1,5-anhydroglucitol (a systemic measure of glucose metabolism). Phospho-AKT
upregulation at week 4 in biopsies confirmed AKT inhibition by GSK2141795. Single
agent activity was observed with a clinical benefit rate of 27% (3/11) and 30%
(3/10) CA125 response in the study's platinum-resistant ovarian patients. AKT
pathway activation by PIK3CA/PIK3R1 mutation did not correlate with clinical
activity, whereas RAS/RAF pathway mutations did segregate with resistance to AKT
inhibition. CONCLUSION: GSK2141795 demonstrated an exposure-response relationship
with decreased (18)F-FDG uptake and is active and tolerable. This study's design
integrating (18)F-FDG PET, pharmacokinetics, and biomarker analyses demonstrates
the potential for clinical development for personalized treatment.
PMID- 26429959
TI - Imaging-Based Treatment Adaptation in Radiation Oncology.
AB - In many tumor types, significant effort is being put into patient-tailored
adaptation of treatment to improve outcome and preferably reduce toxicity. These
opportunities first arose with the introduction of modern irradiation techniques
(e.g., intensity-modulated radiotherapy) combined with functional imaging for
more precise delineation of target volume. On the basis of functional CT, MRI,
and PET results, radiation target volumes are altered during the course of
treatment, or subvolumes inside the primary tumor are defined to enhance the
dosing strategy. Moreover, the probability of complications to normal tissues is
predicted using anatomic or functional imaging, such as in the use of CT or PET
to predict radiation pneumonitis. Besides focusing, monitoring, and adapting
photon therapy for solid tumors, PET also has a role in verifying proton-beam
therapy. This article discusses the current state and remaining challenges of
imaging-based treatment adaptation in radiation oncology.
PMID- 26429958
TI - 68Ga-NOTA-PRGD2 PET/CT for Integrin Imaging in Patients with Lung Cancer.
AB - This study was designed to assess the diagnostic value of (68)Ga-NOTA-PRGD2 (NOTA
PRGD2 is NOTA-PEG4-E[c(RGDfK)]2) PET/CT in lung cancer. METHODS: Ninety-one
patients (48 men and 43 women; age, 22-82 y) with suspected lung lesions on CT
were enrolled with informed consent. Immediately after intravenous injection of
117.7 +/- 37.7 MBq of (68)Ga-NOTA-PRGD2, 15 patients underwent dynamic whole-body
PET/CT scans for 1-2 h, and the remaining 76 patients underwent whole-body PET/CT
scans at 30 +/- 10 min after bolus injection. Each patient also underwent
standard (18)F-FDG PET/CT for comparison. RESULTS: No side effect was found after
(68)Ga-NOTA-PRGD2 injection. (68)Ga-NOTA-PRGD2 was rapidly cleared from the blood
pool and primarily excreted through the urinary system. The standardized uptake
values of proven malignancies were significantly higher than those of the benign
ones. With an average standardized uptake value of greater than 1.3 being
considered malignant, the sensitivity, specificity, and accuracy of (68)Ga-NOTA
PRGD2 PET/CT in diagnosing lung cancer were 83.8% (57/68), 91.3% (21/23), and
85.7% (78/91), respectively. The diagnostic value of (68)Ga-NOTA-PRGD2 for lung
cancer is comparable to that of (18)F-FDG PET/CT. However, (68)Ga-NOTA-PRGD2
PET/CT is more specific than (18)F-FDG PET/CT in assessing lymph node metastasis,
with positive and negative predictive values of 90.0% (27/30) and 93.8%
(121/129), respectively, whereas those of (18)F-FDG PET/CT were 30.2% (29/96) and
90.5% (57/63), respectively. CONCLUSION: This study indicates the efficacy of
(68)Ga-NOTA-PRGD2 PET/CT in lung cancer diagnosis. (68)Ga-NOTA-PRGD2 PET/CT shows
significant advantage over (18)F-FDG PET/CT in judging metastatic lymph nodes
with higher specificity.
PMID- 26429960
TI - Reply: Simplified Methods for Quantification of 18F-Fluoromethylcholine Uptake:
Is SUVAUC,PP Actually an SUV?
PMID- 26429961
TI - 64Cu-DOTATATE for Noninvasive Assessment of Atherosclerosis in Large Arteries and
Its Correlation with Risk Factors: Head-to-Head Comparison with 68Ga-DOTATOC in
60 Patients.
AB - The somatostatin receptor subtype 2 is expressed on macrophages, an abundant cell
type in the atherosclerotic plaque. Visualization of somatostatin receptor
subtype 2, for oncologic purposes, is frequently made using the DOTA-derived
somatostatin analogs DOTATOC or DOTATATE for PET. We aimed to compare the uptake
of the PET tracers (68)Ga-DOTATOC and (64)Cu-DOTATATE in large arteries, in the
assessment of atherosclerosis by noninvasive imaging technique, combining PET and
CT. Further, the correlation of uptake and cardiovascular risk factors was
investigated. METHODS: Sixty consecutive patients with neuroendocrine tumors
underwent both (68)Ga-DOTATOC and (64)Cu-DOTATATE PET/CT scans, in random order.
For each scan, the maximum and mean standardized uptake values (SUVs) were
calculated in 5 arterial segments. In addition, the blood-pool-corrected target
to-background ratio was calculated. Uptake of the tracers was correlated with
cardiovascular risk factors collected from medical records. RESULTS: We found
detectable uptake of both tracers in all arterial segments studied. Uptake of
(64)Cu-DOTATATE was significantly higher than (68)Ga-DOTATOC in the vascular
regions both when calculated as maximum and mean uptake. There was a significant
association between Framingham risk score and the overall maximum uptake of
(64)Cu-DOTATATE using SUV (r = 0.4; P = 0.004) as well as target-to-background
ratio (r = 0.3; P = 0.04), whereas no association was found with (68)Ga-DOTATOC.
The association of risk factors and maximum SUV of (64)Cu-DOTATATE was found
driven by body mass index, smoking, diabetes, and coronary calcium score (P <
0.001, P = 0.01, P = 0.005, and P = 0.03, respectively). CONCLUSION: In a series
of oncologic patients, vascular uptake of (68)Ga-DOTATOC and (64)Cu-DOTATATE was
found, with highest uptake of the latter. Uptake of (64)Cu-DOTATATE, but not of
(68)Ga-DOTATOC, was correlated with cardiovascular risk factors, suggesting a
potential role for (64)Cu-DOTATATE in the assessment of atherosclerosis.
PMID- 26429962
TI - Dual-Receptor-Targeted Radioimmunotherapy of Human Breast Cancer Xenografts in
Athymic Mice Coexpressing HER2 and EGFR Using 177Lu- or 111In-Labeled Bispecific
Radioimmunoconjugates.
AB - One mechanism of resistance to trastuzumab in human epidermal growth factor
receptor-2 (HER2)-positive breast cancer (BC) is increased epidermal growth
factor receptor (EGFR) expression. We have developed (111)In-labeled bispecific
radioimmunoconjugates (bsRICs) that bind HER2 and EGFR on BC cells by linking
trastuzumab Fab fragments through a polyethylene glycol (PEG24) spacer to
epidermal growth factor (EGF). We hypothesized that tumors coexpressing HER2 and
EGFR could be treated by dual-receptor-targeted radioimmunotherapy with these
bsRICs labeled with the beta-particle emitter (177)Lu or the Auger electron
emitter (111)In. METHODS: The binding of (177)Lu-DOTA-Fab-PEG24-EGF to tumor
cells (MDA-MB-231, SK-OV-3, MDA-MB-231/H2N, or TrR1) coexpressing HER2 and EGFR
was assessed in competition assays. The clonogenic survival of these cells was
measured after exposure to (177)Lu-DOTA-Fab-PEG24-EGF or (111)In-DTPA-Fab-PEG24
EGF or to monospecific (177)Lu- or (111)In-labeled trastuzumab Fab or EGF. The
tumor and normal tissue biodistribution of (177)Lu-DOTA-Fab-PEG24-EGF was studied
at 48 h after injection in athymic mice bearing subcutaneous MDA-MB-231/H2N
tumors. Radiation-absorbed doses to tumors and normal tissues were estimated and
compared for (111)In- and (177)Lu-labeled bsRICs. The maximum injected amount of
(177)Lu-DOTA-Fab-PEG24-EGF that caused no observable adverse effects (NOAEL) was
identified in BALB/c mice. Athymic CD1 nu/nu mice bearing subcutaneous
trastuzumab-sensitive MDA-MB-231/H2N or trastuzumab-resistant TrR1 tumors were
treated with (177)Lu-DOTA-Fab-PEG24-EGF or (111)In-DTPA-Fab-PEG24-EGF at the
NOAEL, or with unlabeled immunoconjugates or normal saline. Tumor growth was
evaluated over a period of 49 d. RESULTS: (177)Lu-DOTA-Fab-PEG24-EGF bound
specifically to HER2 and EGFR on tumor cells. Monospecific (177)Lu- and (111)In
labeled trastuzumab Fab or EGF killed tumor cells that predominantly expressed
HER2 or EGFR, respectively, whereas bsRICs were cytotoxic to cells that displayed
either HER2 or EGFR or both receptors. bsRICs were more effective than
monospecific agents. (177)Lu-DOTA-Fab-PEG24-EGF was more cytotoxic than (111)In
DTPA-Fab-PEG24-EGF. The tumor uptake of (177)Lu-DOTA-Fab-PEG24-EGF was 2-fold
greater than (177)Lu-DOTA-trastuzumab Fab or (177)Lu-DOTA-EGF. The NOAEL for
(177)Lu-DOTA-Fab-PEG24-EGF was 11.1 MBq (10 MUg). Trastuzumab-sensitive MDA-MB
231/H2N and trastuzumab-resistant TrR1 tumors were growth-inhibited by (177)Lu
DOTA-Fab-PEG24-EGF or (111)In-DTPA-Fab-PEG24-EGF. Unlabeled immunoconjugates had
no effect on tumor growth. (177)Lu-DOTA-Fab-PEG24-EGF inhibited tumor growth more
effectively than (111)In-DTPA-Fab-PEG24-EGF because of a 9.3-fold-higher
radiation-absorbed dose (55.0 vs. 5.9 Gy, respectively). CONCLUSION: These
results are encouraging for further development of these bsRICs for dual-receptor
targeted radioimmunotherapy of BC coexpressing HER2 and EGFR, including
trastuzumab-resistant tumors.
PMID- 26429963
TI - MAGiC: VOC remains but kids with SCA appear.
AB - In this issue of Blood, Brousseau et al report results from the Magnesium for
Children in Crisis (MAGiC; #NCT01197417) trial. This multicenter, double-blind,
placebo-controlled trial compared the effects of intravenous magnesium to saline
in children with sickle cell anemia (SCA) admitted to the hospital for acute vaso
occlusive pain (VOC). Although magnesium was found to be ineffective, MAGiC
illustrates an effective strategy for rapid and efficient patient accrual in
pediatric SCA studies.
PMID- 26429964
TI - Is the open mouth mightier than the needle?
AB - In this issue of Blood, Bernard et al provide evidence that ibrutinib, the orally
administered inhibitor of Bruton tyrosine kinase (BTK), crosses the blood-brain
barrier and has activity against mantle cell lymphoma (MCL) in the central
nervous system (CNS).
PMID- 26429965
TI - Platelet-derived VWF in the stroke spotlight.
AB - In this issue of Blood, Verhenne et al present data showing the role of platelet
derived von Willebrand factor (VWF) in mediating ischemic stroke injury using a
murine model. They created mice with either endothelial VWF or platelet-derived
VWF and examined each phenotype for bleeding and thrombosis. Their intriguing
findings were that mice lacking platelet-derived VWF, but with adequate
endothelial VWF stores, demonstrated normal hemostasis in a tail bleeding model
and normal carotid artery thrombosis. Mice with only platelet-derived VWF had
defective hemostasis and defective carotid artery thrombosis, but experienced
significant cerebral infarction using a stroke model with middle cerebral artery
occlusion (see figure). In contrast, minimal infarcts were seen for VWF-deficient
mice. These data suggest that platelet-derived VWF plays a specific role in
stroke pathology.
PMID- 26429966
TI - How's your microbiota? Let's check your urine.
AB - In this issue of Blood, Weber and colleagues demonstrate that in the first 10
days following allogeneic hematopoietic transplantation, urinary 3-indoxyl
sulfate is a biomarker of intestinal microbiota health and predicts reduced
intestinal graft-versus-host disease (GVHD) and treatment-related mortality, as
well as improved overall survival.
PMID- 26429967
TI - NOTCH2 missplicing can occur in relation to apoptosis.
PMID- 26429968
TI - An extended dsRBD is required for post-transcriptional modification in human
tRNAs.
AB - In tRNA, dihydrouridine is a conserved modified base generated by the post
transcriptional reduction of uridine. Formation of dihydrouridine 20, located in
the D-loop, is catalyzed by dihydrouridine synthase 2 (Dus2). Human Dus2 (HsDus2)
expression is upregulated in lung cancers, offering a growth advantage throughout
its ability to interact with components of the translation apparatus and inhibit
apoptosis. Here, we report the crystal structure of the individual domains of
HsDus2 and their functional characterization. HsDus2 is organized into three
major modules. The N-terminal catalytic domain contains the flavin cofactor
involved in the reduction of uridine. The second module is the conserved alpha
helical domain known as the tRNA binding domain in HsDus2 homologues. It is
connected via a flexible linker to an unusual extended version of a dsRNA binding
domain (dsRBD). Enzymatic assays and yeast complementation showed that the
catalytic domain binds selectively NADPH but cannot reduce uridine in the absence
of the dsRBD. While in Dus enzymes from bacteria, plants and fungi, tRNA binding
is essentially achieved by the alpha-helical domain, we showed that in HsDus2
this function is carried out by the dsRBD. This is the first reported case of a
tRNA-modifying enzyme carrying a dsRBD used to bind tRNAs.
PMID- 26429969
TI - Genome-wide profiling of nucleosome sensitivity and chromatin accessibility in
Drosophila melanogaster.
AB - Nucleosomal DNA is thought to be generally inaccessible to DNA-binding factors,
such as micrococcal nuclease (MNase). Here, we digest Drosophila chromatin with
high and low concentrations of MNase to reveal two distinct nucleosome types:
MNase-sensitive and MNase-resistant. MNase-resistant nucleosomes assemble on
sequences depleted of A/T and enriched in G/C-containing dinucleotides, whereas
MNase-sensitive nucleosomes form on A/T-rich sequences found at transcription
start and termination sites, enhancers and DNase I hypersensitive sites.
Estimates of nucleosome formation energies indicate that MNase-sensitive
nucleosomes tend to be less stable than MNase-resistant ones. Strikingly, a
decrease in cell growth temperature of about 10 degrees C makes MNase-sensitive
nucleosomes less accessible, suggesting that observed variations in MNase
sensitivity are related to either thermal fluctuations of chromatin fibers or the
activity of enzymatic machinery. In the vicinity of active genes and DNase I
hypersensitive sites nucleosomes are organized into periodic arrays, likely due
to 'phasing' off potential barriers formed by DNA-bound factors or by nucleosomes
anchored to their positions through external interactions. The latter idea is
substantiated by our biophysical model of nucleosome positioning and energetics,
which predicts that nucleosomes immediately downstream of transcription start
sites are anchored and recapitulates nucleosome phasing at active genes
significantly better than sequence-dependent models.
PMID- 26429970
TI - Detection of uracil within DNA using a sensitive labeling method for in vitro and
cellular applications.
AB - The role of uracil in genomic DNA has been recently re-evaluated. It is now
widely accepted to be a physiologically important DNA element in diverse systems
from specific phages to antibody maturation and Drosophila development. Further
relevant investigations would largely benefit from a novel reliable and fast
method to gain quantitative and qualitative information on uracil levels in DNA
both in vitro and in situ, especially since current techniques does not allow in
situ cellular detection. Here, starting from a catalytically inactive uracil-DNA
glycosylase protein, we have designed several uracil sensor fusion proteins. The
designed constructs can be applied as molecular recognition tools that can be
detected with conventional antibodies in dot-blot applications and may also serve
as in situ uracil-DNA sensors in cellular techniques. Our method is verified on
numerous prokaryotic and eukaryotic cellular systems. The method is easy to use
and can be applied in a high-throughput manner. It does not require expensive
equipment or complex know-how, facilitating its easy implementation in any basic
molecular biology laboratory. Elevated genomic uracil levels from cells of
diverse genetic backgrounds and/or treated with different drugs can be
demonstrated also in situ, within the cell.
PMID- 26429972
TI - Nuclear domain 'knock-in' screen for the evaluation and identification of small
molecule enhancers of CRISPR-based genome editing.
AB - CRISPR is a genome-editing platform that makes use of the bacterially-derived
endonuclease Cas9 to introduce DNA double-strand breaks at precise locations in
the genome using complementary guide RNAs. We developed a nuclear domain knock-in
screen, whereby the insertion of a gene encoding the green fluorescent protein
variant Clover is inserted by Cas9-mediated homology directed repair (HDR) within
the first exon of genes that are required for the structural integrity of
subnuclear domains such as the nuclear lamina and promyelocytic leukemia nuclear
bodies (PML NBs). Using this approach, we compared strategies for enhancing
CRISPR-mediated HDR, focusing on known genes and small molecules that impact non
homologous end joining (NHEJ) and homologous recombination (HR). Ultimately, we
identified the small molecule RS-1 as a potent enhancer of CRISPR-based genome
editing, enhancing HDR 3- to 6-fold depending on the locus and transfection
method. We also characterized U2OS human osteosarcoma cells expressing Clover
tagged PML and demonstrate that this strategy generates cell lines with PML NBs
that are structurally and functionally similar to bodies in the parental cell
line. Thus, the nuclear domain knock-in screen that we describe provides a simple
means of rapidly evaluating methods and small molecules that have the potential
to enhance Cas9-mediated HDR.
PMID- 26429971
TI - Molecular basis for the substrate specificity and catalytic mechanism of thymine
7-hydroxylase in fungi.
AB - TET proteins play a vital role in active DNA demethylation in mammals and thus
have important functions in many essential cellular processes. The chemistry for
the conversion of 5mC to 5hmC, 5fC and 5caC catalysed by TET proteins is similar
to that of T to 5hmU, 5fU and 5caU catalysed by thymine-7-hydroxylase (T7H) in
the nucleotide anabolism in fungi. Here, we report the crystal structures and
biochemical properties of Neurospora crassa T7H. T7H can bind the substrates only
in the presence of cosubstrate, and binding of different substrates does not
induce notable conformational changes. T7H exhibits comparable binding affinity
for T and 5hmU, but 3-fold lower affinity for 5fU. Residues Phe292, Tyr217 and
Arg190 play critical roles in substrate binding and catalysis, and the
interactions of the C5 modification group of substrates with the cosubstrate and
enzyme contribute to the slightly varied binding affinity and activity towards
different substrates. After the catalysis, the products are released and new
cosubstrate and substrate are reloaded to conduct the next oxidation reaction.
Our data reveal the molecular basis for substrate specificity and catalytic
mechanism of T7H and provide new insights into the molecular mechanism of
substrate recognition and catalysis of TET proteins.
PMID- 26429973
TI - Risk Factors for Puncture Site Complications After Endovascular Procedures in
Patients With Peripheral Arterial Disease.
AB - OBJECTIVE: To compare femoral access site closure techniques and to highlight
risk factors for puncture site complications after lower extremity endovascular
procedures. METHODS: This retrospective study included 787 patients. Procedures
were performed according to a standardized protocol. Puncture site complications
within 24 hours were regarded as study end points. RESULTS: Ninety (11.5%)
puncture site complications were registered. Conventional manual compression (n =
87, 11.1%) was significantly associated with puncture site complications (odds
ratio [OR] 2.08, P = .03). Body mass index > 25 kg/m(2) (OR 0.54, P = .01) and
prothrombin time > 70% (OR 0.38, P = .04) were protective. All bleeding occurred
in procedures >45 minutes. Blood pressure >200 mm Hg and below the knee (BTK)
procedures were strong predictors for access site complications (OR 4.21, P = .01
and OR 3.33, P = .02). CONCLUSIONS: We observed an inferiority of conventional
manual compression. Age, procedure duration > 45 minutes, BTK procedures,
uncontrolled hypertension, and impaired coagulation were risk factors.
PMID- 26429974
TI - Multicentre randomized controlled trial of angiotensin-converting enzyme
inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the
STOP-ACEi trial.
AB - BACKGROUND: Blood pressure (BP) control and reduction of urinary protein
excretion using agents that block the renin-angiotensin aldosterone system are
the mainstay of therapy for chronic kidney disease (CKD). Research has confirmed
the benefits in mild CKD, but data on angiotensin-converting enzyme inhibitor
(ACEi) or angiotensin receptor blocker (ARB) use in advanced CKD are lacking. In
the STOP-ACEi trial, we aim to confirm preliminary findings which suggest that
withdrawal of ACEi/ARB treatment can stabilize or even improve renal function in
patients with advanced progressive CKD. METHODS: The STOP-ACEi trial (trial
registration: current controlled trials, ISRCTN62869767) is an investigator-led
multicentre open-label, randomized controlled clinical trial of 410 participants
with advanced (Stage 4 or 5) progressive CKD receiving ACEi, ARBs or both.
Patients will be randomized in a 1:1 ratio to either discontinue ACEi, ARB or
combination of both (experimental arm) or continue ACEi, ARB or combination of
both (control arm). Patients will be followed up at 3 monthly intervals for 3
years. The primary outcome measure is eGFR at 3 years. Secondary outcome measures
include the number of renal events, participant quality of life and physical
functioning, hospitalization rates, BP and laboratory measures, including serum
cystatin-C. Safety will be assessed to ensure that withdrawal of these treatments
does not cause excess harm or increase mortality or cardiovascular events such as
heart failure, myocardial infarction or stroke. RESULTS: The rationale and trial
design are presented here. The results of this trial will show whether
discontinuation of ACEi/ARBs can improve or stabilize renal function in patients
with advanced progressive CKD. It will show whether this simple intervention can
improve laboratory and clinical outcomes, including progression to end-stage
renal disease, without causing an increase in cardiovascular events.
PMID- 26429975
TI - MDS-associated somatic mutations and clonal hematopoiesis are common in
idiopathic cytopenias of undetermined significance.
AB - Establishing a diagnosis in patients suspected of having a myelodysplastic
syndrome (MDS) can be challenging and could be informed by the identification of
somatic mutations. We performed a prospective study to examine the frequency and
types of mutations encountered in 144 patients with unexplained cytopenias. Based
on bone marrow findings, 17% were diagnosed with MDS, 15% with idiopathic
cytopenias of undetermined significance (ICUS) and some evidence of dysplasia,
and 69% with ICUS and no dysplasia. Bone marrow DNA was sequenced for mutations
in 22 frequently mutated myeloid malignancy genes. Somatic mutations were
identified in 71% of MDS patients, 62% of patients with ICUS and some dysplasia,
and 20% of ICUS patients and no dysplasia. In total, 35% of ICUS patients carried
a somatic mutation or chromosomal abnormality indicative of clonal hematopoiesis.
We validated these results in a cohort of 91 lower-risk MDS and 249 ICUS cases
identified over a 6-month interval. Mutations were found in 79% of those with
MDS, in 45% of those with ICUS with dysplasia, and in 17% of those with ICUS
without dysplasia. The spectrum of mutated genes was similar with the exception
of SF3B1 which was rarely mutated in patients without dysplasia. Variant allele
fractions were comparable between clonal ICUS (CCUS) and MDS as were mean age and
blood counts. We demonstrate that CCUS is a more frequent diagnosis than MDS in
cytopenic patients. Clinical and mutational features are similar in these groups
and may have diagnostic utility once outcomes in CCUS patients are better
understood.
PMID- 26429978
TI - AACR Cancer Progress Report 2015: Transforming Lives Through Precision Medicine.
PMID- 26429979
TI - CCR 20th Anniversary Commentary: Bevacizumab in the Treatment of Glioblastoma-
The Progress and the Limitations.
AB - Vredenburgh and colleagues conducted the first phase II study of bevacizumab plus
irinotecan in recurrent malignant glioma, confirming the safety and efficacy of
bevacizumab. This study, which was published in the February 15, 2007, issue of
Clinical Cancer Research, was a stepping stone for subsequent research, leading
to regulatory approval of bevacizumab for recurrent glioblastoma.
PMID- 26429976
TI - High DeltaNp73/TAp73 ratio is associated with poor prognosis in acute
promyelocytic leukemia.
AB - The TP73 gene transcript is alternatively spliced and translated into the
transcriptionally active (TAp73) or inactive (DeltaNp73) isoforms, with opposite
effects on the expression of p53 target genes and on apoptosis induction. The
imbalance between DeltaNp73 and TAp73 may contribute to tumorigenesis and
resistance to chemotherapy in human cancers, including hematologic malignancies.
In acute promyelocytic leukemia (APL), both isoforms are expressed, but their
relevance in determining response to therapy and contribution to leukemogenesis
remains unknown. Here, we provide the first evidence that a higher
DeltaNp73/TAp73 RNA expression ratio is associated with lower survival, lower
disease-free survival, and higher risk of relapse in patients with APL
homogeneously treated with all-trans retinoic acid and anthracycline-based
chemotherapy, according to the International Consortium on Acute Promyelocytic
Leukemia (IC-APL) study. Cox proportional hazards modeling showed that a high
DeltaNp73/TAp73 ratio was independently associated with shorter overall survival
(hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P = .0035). Our data
support the hypothesis that the DeltaNp73/TAp73 ratio is an important determinant
of clinical response in APL and may offer a therapeutic target for enhancing
chemosensitivity in blast cells.
PMID- 26429980
TI - Molecular Pathways: Clinical Applications and Future Direction of Insulin-like
Growth Factor-1 Receptor Pathway Blockade.
AB - The IGF1R signaling pathway is a complex and tightly regulated network that is
critical for cell proliferation, growth, and survival. IGF1R is a potential
therapeutic target for patients with many different malignancies. This brief
review summarizes the results of clinical trials targeting the IGF1R pathway in
patients with breast cancer, sarcoma, and non-small cell lung cancer (NSCLC).
Therapeutic agents discussed include both monoclonal antibodies to IGF1R
(dalotuzumab, figitumumab, cixutumumab, ganitumab, R1507, AVE1642) and newer
IGF1R pathway targeting strategies, including monoclonal antibodies to IGF1 and
IGF2 (MEDI-573 and BI 836845) and a small-molecule tyrosine kinase inhibitor of
IGF1R (linsitinib). The pullback of trials in patients with breast cancer and
NSCLC based on several large negative trials is noted and contrasted with the
sustained success of IGF1R inhibitor monotherapy in a subset of patients with
sarcoma. Several different biomarkers have been examined in these trials with
varying levels of success, including tumor expression of IGF1R and its pathway
components, serum IGF ligand levels, alternate pathway activation, and specific
molecular signatures of IGF1R pathway dependence. However, there remains a
critical need to define predictive biomarkers in order to identify patients who
may benefit from IGF1R-directed therapies. Ongoing research focuses on uncovering
such biomarkers and elucidating mechanisms of resistance, as this therapeutic
target is currently being analyzed from the bedside to bench.
PMID- 26429981
TI - Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4
Antibody, KW-0761, in Cancer Patients.
AB - PURPOSE: FoxP3(+) Tregs inhibit immune responses against tumors. KW-0761 is a
humanized anti-human CCR4 monoclonal antibody (mAb) that has antibody-dependent
cellular cytotoxicity activity. Depletion of CCR4-expressing FoxP3(+) CD4 Tregs
by KW-0761 infusion was investigated in solid cancer patients. EXPERIMENTAL
DESIGN: We conducted a phase Ia clinical trial of KW-0761 infusion in 7 lung and
3 esophageal cancer patients. Toxicity, clinical efficacy, changes in lymphocyte
subpopulations, including Tregs, and induction of immune responses were analyzed.
RESULTS: The results showed that KW-0761 infusion in a dose range between 0.1
mg/kg and 1.0 mg/kg was safe and well tolerated. No dose-limiting toxicity was
observed. Four of 10 patients showed stable disease during treatment and were
long survivors. The monitoring of FoxP3(+) Tregs in the peripheral blood
mononuclear cells during treatment indicated efficient depletion of those cells,
even at the lowest dose of 0.1 mg/kg used. The reduction in Th 1 CD4 T cells and
CD8 T cells was limited, whereas a significant reduction was observed with Th 2
and Th 17 CD4 T cells. Immune responses to cancer/testis (CT) antigens and an
autoantibody response to thyroid peroxidase were observed in some patients.
CONCLUSIONS: The findings showed Tregs depletion and the possible occurrence of
an immune response following KW-0761 infusion. Combined use of KW-0761 to deplete
FoxP3(+) Tregs with other immunotherapies, such as cancer vaccines or checkpoint
inhibitors, is a promising approach to augment immune responses.
PMID- 26429983
TI - Ancient Retrovirus Targeted by Engineered T Cells in Melanoma--Letter.
PMID- 26429982
TI - Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells
Directed against E6.
AB - PURPOSE: The E6 and E7 oncoproteins of HPV-associated epithelial cancers are in
principle ideal immunotherapeutic targets, but evidence that T cells specific for
these antigens can recognize and kill HPV(+) tumor cells is limited. We sought to
determine whether TCR gene engineered T cells directed against an HPV oncoprotein
can successfully target HPV(+) tumor cells. EXPERIMENTAL DESIGN: T-cell responses
against the HPV-16 oncoproteins were investigated in a patient with an ongoing 22
month disease-free interval after her second resection of distant metastatic anal
cancer. T cells genetically engineered to express an oncoprotein-specific TCR
from this patient's tumor-infiltrating T cells were tested for specific
reactivity against HPV(+) epithelial tumor cells. RESULTS: We identified, from an
excised metastatic anal cancer tumor, T cells that recognized an HLA-A*02:01
restricted epitope of HPV-16 E6. The frequency of the dominant T-cell clonotype
from these cells was approximately 400-fold greater in the patient's tumor than
in her peripheral blood. T cells genetically engineered to express the TCR from
this clonotype displayed high avidity for an HLA-A*02:01-restricted epitope of
HPV-16, and they showed specific recognition and killing of HPV-16(+) cervical,
and head and neck cancer cell lines. CONCLUSIONS: These findings demonstrate that
HPV-16(+) tumors can be targeted by E6-specific TCR gene engineered T cells, and
they provide the foundation for a novel cellular therapy directed against HPV
16(+) malignancies, including cervical, oropharyngeal, anal, vulvar, vaginal, and
penile cancers.
PMID- 26429984
TI - Correction: Pancreatic Cancer-Derived Exosomes Causes Paraneoplastic beta-cell
Dysfunction.
PMID- 26429985
TI - Correction: The Prostate Cancer Susceptibility Variant rs2735839 Near KLK3 Gene
Is Associated with Aggressive Prostate Cancer and Can Stratify Gleason Score 7
Patients.
PMID- 26429986
TI - Will LHINs ever become the "eyes and ears" of the Health Minister for local
community wisdom?
AB - This commentary reflects on the intent of the legislation establishing the Local
Health Integration Networks (LHINs) and comments on the performance gap between
the vision for what could have been and the actual performance. A nine-point
action plan to restore the LHINs' potential role as a positive force for health
system integration and transformation at the local level is provided.
PMID- 26429987
TI - Are LHINs influencing the patient experience in Ontario?
AB - Patient engagement and patient experience have become an important focal point
for health policy development in Ontario. Many healthcare delivery and planning
organizations are exploring how to use patient experience information and data to
improve the quality of their services and processes. Local Health Integration
Networks (LHINs) are also beginning to include patient experience as a measure of
local health system improvement. This article reviews the role of LHINs in
developing patient experience information over their 10 year history and
highlights current initiatives.
PMID- 26429988
TI - The LHIN adventure: The journey continues.
AB - The Local Health Integration Network (LHIN) adventure began 10 years ago with the
intent of transforming the Ontario health system by providing system-based
leadership and building collaborative capacity among health service providers.
The LHIN construct has continued its evolution during this time and is still in
the midst of testing and reshaping the boundaries of its mandate and authority.
Working closely and in tandem with the Ministry of Health and Long-Term Care,
LHINs have grappled with governance, funding, integration, and engagement,
changing the nature of relationships and the dynamics inherent across the health
system. The next decade holds considerable promise for LHINs and the health
system in Ontario as a whole.
PMID- 26429989
TI - [Les inegalites dans l'acces aux soins du cancer au Canada: un point de vue
ethique].
AB - La capacite d'offrir des soins du cancer de qualite depend en grande partie de
l'accessibilite des services a ceux qui en ont besoin. Dans l'etat actuel des
choses, on constate des disparites en matiere d'acces aux services de
cancerologie au Canada, ce qui constitue un probleme sur le plan de l'ethique. Le
present article fait ressortir les points de vue ethiques et strategiques lies a
l'equite dans l'acces aux soins du cancer au Canada. S'inspirant des principes de
la bioethique, soit la beneficience, la non-maleficience et la justice, plusieurs
strategies sont recommandees pour ameliorer l'acces aux soins du cancer au pays.
PMID- 26429990
TI - By 2025 a million more UK people will be living with life threatening conditions,
warns royal college.
PMID- 26429992
TI - GPs are inadequately equipped to manage growing demand for cancer care, study
warns.
PMID- 26429991
TI - AACR Cancer Progress Report 2015.
PMID- 26429994
TI - Response to Letter Regarding Article, "Hypotension During Endovascular Treatment
of Ischemic Stroke Is a Risk Factor for Poor Neurological Outcome".
PMID- 26429993
TI - Honoring Roots in Multiple Worlds: Professionals' Perspectives on Healthy
Development of Latino Youth.
AB - PURPOSE: To obtain contextualized insights from professionals regarding factors
that contribute to or inhibit the healthy development of Latino youth. METHOD: A
community-engaged study in which semistructured in-depth interviews were
conducted with 30 professionals who work extensively with Latino youth in urban
clinics, schools, and other community-based settings. RESULTS: Every key
informant expressed opinions regarding factors that contribute to healthy
development of Latino youth, ranging from cultural identity and a sense of
belonging to family connectedness and adult role models. Contributing and
inhibiting factors were characterized by being either intrinsic to the individual
(e.g., sense of belonging, hope) or extrinsic (e.g., family support and love,
community support). CONCLUSION: Recognition of and appreciation for the
importance of cultural influences in the lives of Latino youth is a critical
starting point on which professionals must build to respectfully and successfully
encourage healthy youth development. Factors that contribute to the healthy
development of Latino youth range from cultural identity and cultural pride to
family connectedness, adult role models, and a sense of belonging. In working
with Latino young people, professionals must recognize and appreciate cultural
influences as foundational to this population's health and well-being.
PMID- 26429995
TI - Brief History of Endovascular Acute Ischemic Stroke Treatment.
PMID- 26429996
TI - Letter by Zhang et al Regarding Article, "Hypotension During Endovascular
Treatment of Ischemic Stroke Is a Risk Factor for Poor Neurological Outcome".
PMID- 26429997
TI - Re: "analyzing seasonal variations in suicide with Fourier Poisson time-series
regression: a registry-based study From Norway, 1969-2007".
PMID- 26429998
TI - Asymptotically Unbiased Estimation of Exposure Odds Ratios in Complete Records
Logistic Regression.
AB - Missing data are a commonly occurring threat to the validity and efficiency of
epidemiologic studies. Perhaps the most common approach to handling missing data
is to simply drop those records with 1 or more missing values, in so-called
"complete records" or "complete case" analysis. In this paper, we bring together
earlier-derived yet perhaps now somewhat neglected results which show that a
logistic regression complete records analysis can provide asymptotically unbiased
estimates of the association of an exposure of interest with an outcome, adjusted
for a number of confounders, under a surprisingly wide range of missing-data
assumptions. We give detailed guidance describing how the observed data can be
used to judge the plausibility of these assumptions. The results mean that in
large epidemiologic studies which are affected by missing data and analyzed by
logistic regression, exposure associations may be estimated without bias in a
number of settings where researchers might otherwise assume that bias would
occur.
PMID- 26429999
TI - The authors reply.
PMID- 26430000
TI - Former US army physician sentenced to prison for medical device kickback scheme.
PMID- 26430001
TI - Training and education: new ways and new challenges.
PMID- 26430002
TI - The treatment of arthritis of the wrist.
AB - Arthritis of the wrist is a painful disabling condition that has various causes
and presentations. The traditional treatment has been a total wrist fusion at a
price of the elimination of movement. However, forms of treatment which allow the
preservation of movement are now preferred. Modern arthroplasties of the wrist
are still not sufficiently robust to meet the demands of many patients, nor do
they restore normal kinematics of the wrist. A preferable compromise may be
selective excision and partial fusion of the wrist using knowledge of the
aetiology and pattern of degenerative change to identify which joints can be
sacrificed and which can be preserved. This article provides an overview of the
treatment options available for patients with arthritis of the wrist and an
algorithm for selecting an appropriate surgical strategy.
PMID- 26430003
TI - Evidence-based surgical training in orthopaedics: how many arthroscopies of the
knee are needed to achieve consultant level performance?
AB - Despite being one of the most common orthopaedic operations, it is still not
known how many arthroscopies of the knee must be performed during training in
order to develop the skills required to become a Consultant. A total of 54
subjects were divided into five groups according to clinical experience: Novices
(n = 10), Junior trainees (n = 10), Registrars (n = 18), Fellows (n = 10) and
Consultants (n = 6). After viewing an instructional presentation, each subject
performed a simple diagnostic arthroscopy of the knee on a simulator with
visualisation and probing of ten anatomical landmarks. Performance was assessed
using a validated global rating scale (GRS). Comparisons were made against
clinical experience measured by the number of arthroscopies which had been
undertaken, and ROC curve analysis was used to determine the number of procedures
needed to perform at the level of the Consultants. There were marked differences
between the groups. There was significant improvement in performance with
increasing experience (p < 0.05). ROC curve analysis identified that
approximately 170 procedures were required to achieve the level of skills of a
Consultant. We suggest that this approach to identify what represents the level
of surgical skills of a Consultant should be used more widely so that standards
of training are maintained through the development of an evidenced-based
curriculum.
PMID- 26430004
TI - Arthroscopy of the hip for patients with mild to moderate developmental dysplasia
of the hip and femoroacetabular impingement: Outcomes following hip arthroscopy
for treatment of chondrolabral damage.
AB - The purpose of this study was to determine patient-reported outcomes of patients
with mild to moderate developmental dysplasia of the hip (DDH) and
femoroacetabular impingement (FAI) undergoing arthroscopy of the hip in the
treatment of chondrolabral pathology. A total of 28 patients with a centre-edge
angle between 15 degrees and 19 degrees were identified from an institutional
database. Their mean age was 34 years (18 to 53), with 12 female and 16 male
patients. All underwent labral treatment and concomitant correction of FAI. There
were nine reoperations, with two patients requiring revision arthroscopy, two
requiring periacetabular osteotomy and five needing total hip arthroplasty.
Patients who required further major surgery were more likely to be older, male,
and to have more severe DDH with a larger alpha angle and decreased joint space.
At a mean follow-up of 42 months (24 to 89), the mean modified Harris hip score
improved from 59 (20 to 98) to 82 (45 to 100; p < 0.001). The mean Western
Ontario and McMaster Universities Osteoarthritis Index score improved from 30 (1
to 61) to 16 (0 to 43; p < 0.001). Median patient satisfaction was 9.0/10 (1 to
10). Patients reported excellent improvement in function following arthroscopy of
the hip. This study shows that with proper patient selection, arthroscopy of the
hip can be successful in the young patient with mild to moderate DDH and FAI.
PMID- 26430005
TI - Comparison of contemporary periacetabular osteotomy for hip dysplasia with total
hip arthroplasty for hip osteoarthritis.
AB - We report patient-reported outcomes and complications associated with
contemporary periacetabular osteotomy (PAO) surgery in treating symptomatic
acetabular dysplasia and compare these outcomes with total hip arthroplasty (THA)
in patients with similar demographic details. Two consecutive cohorts included
patients between aged 18 to 40 years who had undergone either PAO (100 hips; 24
male, 76 female) or THA (55 hips; 18 male, 37 female). At a mean follow-up of 5.9
years (2 to 13), there was significant improvement in the modified Harris hip
pain (p < 0.001, PAO and p < 0.001, THA), function (p < 0.001, PAO and p = 0.001,
THA), and total scores (p < 0.001, PAO and p < 0.001, THA) within each cohort.
There were no significant differences in the clinical outcome scores between the
groups. Complication rates were low and similar in each cohort (p = 0.68).
Similar to THA, contemporary PAO surgery is a clinically effective procedure that
improves function and activity levels, provides pain relief and is associated
with an acceptable complication rate.
PMID- 26430006
TI - A longitudinal study of MARS MRI scanning of soft-tissue lesions around metal-on
metal total hip arthroplasties and disease progression.
AB - We investigated the changes seen on serial metal artefact reduction magnetic
resonance imaging scans (MARS-MRI) of metal-on-metal total hip arthroplasties
(MoM THAs). In total 155 THAs, in 35 male and 100 female patients (mean age 70.4
years, 42 to 91), underwent at least two MRI scans at a mean interval of 14.6
months (2.6 to 57.1), at a mean of 48.2 months (3.5 to 93.3) after primary hip
surgery. Scans were graded using a modification of the Oxford classification.
Progression of disease was defined as an increase in grade or a minimum 10%
increase in fluid lesion volume at second scan. A total of 16 hips (30%)
initially classified as 'normal' developed an abnormality on the second scan. Of
those with 'isolated trochanteric fluid' 9 (47%) underwent disease progression,
as did 7 (58%) of 'effusions'. A total of 54 (77%) of hips initially classified
as showing adverse reactions to metal debris (ARMD) progressed, with higher rates
of progression in higher grades. Disease progression was associated with high
blood cobalt levels or an irregular pseudocapsule lining at the initial scan.
There was no association with changes in functional scores. Adverse reactions to
metal debris in MoM THAs may not be as benign as previous reports have suggested.
Close radiological follow-up is recommended, particularly in high-risk groups.
PMID- 26430007
TI - Acetabular revision with impaction bone grafting and a cemented polyethylene
acetabular component: comparison of the Kaplan-Meier analysis to the competing
risk analysis in 62 revisions with 25 to 30 years follow-up.
AB - We present the results of 62 consecutive acetabular revisions using impaction
bone grafting and a cemented polyethylene acetabular component in 58 patients (13
men and 45 women) after a mean follow-up of 27 years (25 to 30). All patients
were prospectively followed. The mean age at revision was 59.2 years (23 to 82).
We performed Kaplan-Meier (KM) analysis and also a Competing Risk (CR) analysis
because with long-term follow-up, the presence of a competing event (i.e. death)
prevents the occurrence of the endpoint of re-revision. A total of 48 patients
(52 hips) had died or had been re-revised at final review in March 2011. None of
the deaths were related to the surgery. The mean Harris hip score of the ten
surviving hips in ten patients was 76 points (45 to 99). The KM survivorship at
25 years for the endpoint 're-revision for any reason' was 58.0% (95% confidence
interval (CI) 38 to 73) and for 're-revision for aseptic loosening' 72.1% (95% CI
51 to 85). With the CR analysis we calculated the KM analysis overestimates the
failure rate with respectively 74% and 93% for these endpoints. The current study
shows that acetabular impaction bone grafting revisions provide good clinical
results at over 25 years.
PMID- 26430008
TI - Neurolysis for the treatment of sciatic nerve palsy associated with total hip
arthroplasty.
AB - Sciatic nerve palsy following total hip arthroplasty (THA) is a relatively rare
yet potentially devastating complication. The purpose of this case series was to
report the results of patients with a sciatic nerve palsy who presented between
2000 and 2010, following primary and revision THA and were treated with
neurolysis. A retrospective review was made of 12 patients (eight women and four
men), with sciatic nerve palsy following THA. The mean age of the patients was
62.7 years (50 to 72; standard deviation 6.9). They underwent interfascicular
neurolysis for sciatic nerve palsy, after failing a trial of non-operative
treatment for a minimum of six months. Following surgery, a statistically and
clinically significant improvement in motor function was seen in all patients.
The mean peroneal nerve score function improved from 0.42 (0 to 3) to 3 (1 to 5)
(p < 0.001). The mean tibial nerve motor function score improved from 1.75 (1 to
4) to 3.92 (3 to 5) (p = 0.02).The mean improvement in sensory function was a
clinically negligible 1 out of 5 in all patients. In total, 11 patients reported
improvement in their pain following surgery. We conclude that neurolysis of the
sciatic nerve has a favourable prognosis in patients with a sciatic nerve palsy
following THA. Our findings suggest that surgery should not be delayed for > 12
months following injury.
PMID- 26430009
TI - Quantification of material loss from the neck piece taper junctions of a
bimodular primary hip prosthesis. A retrieval study from 27 failed Rejuvenate
bimodular hip arthroplasties.
AB - The early failure and revision of bimodular primary total hip arthroplasty
prostheses requires the identification of the risk factors for material loss and
wear at the taper junctions through taper wear analysis. Deviations in taper
geometries between revised and pristine modular neck tapers were determined using
high resolution tactile measurements. A new algorithm was developed and validated
to allow the quantitative analysis of material loss, complementing the standard
visual inspection currently used. The algorithm was applied to a sample of 27
retrievals (in situ from 2.9 to 38.1 months) of the withdrawn Rejuvenate modular
prosthesis. The mean wear volumes on the flat distal neck piece taper was 3.35
mm(3) (0.55 to 7.57), mainly occurring in a characteristic pattern in areas with
high mechanical loading. Wear volume tended to increase with time to revision (r2
= 0.423, p = 0.001). Implant and patient specific data (offset, stem size,
patient's mass, age and body mass index) did not correlate with the amount of
material loss observed (p > 0.078). Bilaterally revised implants showed higher
amounts of combined total material loss and similar wear patterns on both sides.
The consistent wear pattern found in this study has not been reported previously,
suggesting that the device design and materials are associated with the failure
of this prosthesis.
PMID- 26430010
TI - The five-year radiological results of the uncemented Oxford medial compartment
knee arthroplasty.
AB - This study reports on the first 150 consecutive Oxford cementless
unicompartmental knee arthroplasties (UKA) performed in an independent centre
(126 patients). All eligible patients had functional scores (Oxford knee score
and high activity arthroplasty score) recorded pre-operatively and at two- and
five-years of follow-up. Fluoroscopically aligned radiographs were taken at five
years and analysed for any evidence of radiolucent lines (RLLs), subsidence or
loosening. The mean age of the cohort was 63.6 years (39 to 86) with 81 (53.1%)
males. Excellent functional scores were maintained at five years and there were
no progressive RLLs demonstrated on radiographs. Two patients underwent revision
to a total knee arthroplasty giving a revision rate of 0.23/100 (95% confidence
interval 0.03 to 0.84) component years with overall component survivorship of
98.7% at five years. There were a further four patients who underwent further
surgery on the same knee, two underwent bearing exchanges for dislocation and two
underwent lateral UKAs for disease progression. This was a marked improvement
from other UKAs reported in New Zealand Joint Registry data and supports the
designing centre's early results.
PMID- 26430011
TI - Ray amputation for the treatment of foot macrodactyly in children.
AB - Macrodactyly of the foot is a rare but disabling condition. We present the
results of surgery on 18 feet of 16 patients, who underwent ray amputation and
were followed-up for more than two years at a mean of 80 months (25 to 198). We
radiologically measured the intermetatarsal width and forefoot area pre
operatively and at six weeks and two years after surgery. We also evaluated the
clinical results using the Oxford Ankle Foot Questionnaire for children (OxAFQ-C)
and the Questionnaire for Foot Macrodactyly. The intermetatarsal width and
forefoot area ratios were significantly decreased after surgery. The mean OxAFQ-C
score was 42 (16 to 57) pre-operatively, improving to 47 (5 to 60) at two years
post-operatively (p = 0.021). The mean questionnaire for Foot Macrodactyly score
two years after surgery was 8 (6 to 10). Ray amputation gave a measurable
reduction in foot size with excellent functional results. For patients with
metatarsal involvement, a motionless toe, or involvement of multiple digits, ray
amputation is a clinically effective option which is acceptable to patients.
PMID- 26430012
TI - Defining the role of intramedullary nailing for fractures of the distal radius: a
systematic review.
AB - This article is a systematic review of the published literature about the
biomechanics, functional outcome and complications of intramedullary nailing of
fractures of the distal radius. We searched the Medline and EMBASE databases and
included all studies which reported the outcome of intramedullary (IM) nailing of
fractures of the distal radius. Data about functional outcome, range of movement
(ROM), strength and complications, were extracted. The studies included were
appraised independently by both authors using a validated quality assessment
scale for non-controlled studies and the CONSORT statement for randomised
controlled trials (RCTs). The search strategy revealed 785 studies, of which 16
were included for full paper review. These included three biomechanical studies,
eight case series and five randomised controlled trials (RCTs). The biomechanical
studies concluded that IM nails were at least as strong as locking plates. The
clinical studies reported that IM nailing gave a comparable ROM, functional
outcome and grip strength to other fixation techniques. However, the mean
complication rate of intramedullary nailing was 17.6% (0% to 50%). This is higher
than the rates reported in contemporary studies for volar plating. It raises
concerns about the role of intramedullary nailing, particularly when comparative
studies have failed to show that it has any major advantage over other
techniques. Further adequately powered RCTs comparing the technique to both volar
plating and percutaneous wire fixation are needed.
PMID- 26430013
TI - Hemiarthroplasty for irreparable distal humeral fractures: medium-term follow-up
of 42 patients.
AB - We report our experience of performing an elbow hemiarthroplasty in the treatment
of comminuted distal humeral fractures in the elderly patients. A cohort of 42
patients (three men and 39 women, mean age 72; 56 to 84) were reviewed at a mean
of 34.3 months (24 to 61) after surgery. Functional outcome was measured with the
Mayo Elbow Performance Score (MEPS) and range of movement. The disabilities of
the arm, shoulder and hand questionnaire (DASH) was used as a patient rated
evaluation. Complications and ulnar nerve function were recorded. Plain
radiographs were obtained to assess prosthetic loosening, olecranon wear and
heterotopic bone formation. The mean extension deficit was 23.5 degrees (0
degrees to 60 degrees ) and mean flexion was 126.8 degrees (90 degrees to 145
degrees ) giving a mean arc of 105.5 degrees (60 degrees to 145 degrees ). The
mean MEPS was 90 (50 to 100) and a mean DASH score of 20 (0 to 63). Four patients
had additional surgery for limited range of movement and one for partial
instability. One elbow was revised due to loosening, two patients had sensory
ulnar nerve symptoms, and radiographic signs of mild olecranon wear was noted in
five patients. Elbow hemiarthroplasty for comminuted intra-articular distal
humeral fractures produces reliable medium-term results with functional outcome
and complication rates, comparable with open reduction and internal fixation and
total elbow arthroplasty.
PMID- 26430014
TI - Age-related differences in the use of total shoulder arthroplasty over time: use
and outcomes.
AB - We assessed the age-related differences in the use of total shoulder arthroplasty
(TSA) and outcomes, and associated time-trends using the United States Nationwide
Inpatient Sample (NIS) between 1998 and 2010. Age was categorised as < 50, 50 to
64, 65 to 79 and >= 80 years. Time-trends in the use of TSA were compared using
logistic regression or the Cochran Armitage test. The overall use of TSA
increased from 2.96/100 000 in 1998 to 12.68/100,000 in 2010. Significantly lower
rates were noted between 2009 and 2010, compared with between 1998 and 2000, for:
mortality, 0.1% versus 0.2% (p = 0.004); discharge to an inpatient facility,
13.3% versus 14.5% (p = 0.039), and hospital stay > median, 29.4% versus 51.2% (p
< 0.001). The rates of use of TSA/100,000 by age groups, < 50, 50 to 64, 65 to 79
and >= 80 years were: 0.32, 4.62, 17.82 and 12.56, respectively in 1998 (p <
0.001); and 0.65, 17.49, 75.27 and 49.05, respectively in 2010 (p < 0.001) with
an increasing age-related difference over time (p < 0.001). Across the age
categories, there were significant differences in the proportion: discharged to
an inpatient facility, 3.2% versus 4.2% versus 14.7% versus 36.5%, respectively
in 1998 (p < 0.001) and 1.8% versus 4.3% versus 12.5% versus 35.5%, respectively
in 2010 (p < 0.001) and the proportion with hospital stay > median, 39.7% versus
40.2% versus 53% versus 69%, respectively in 1998 (p < 0.001) and 17.2% versus
20.6% versus 28.7% versus 50.7%, respectively in 2010 (p < 0.001). In a
nationally representative sample, we noted a time-related increase in the use of
TSA and increasing age-related differences in outcomes indicating a changing
epidemiology of the use of TSA. Age-related differences in outcomes suggest that
attention should focus on groups with the worst outcomes.
PMID- 26430015
TI - Cauda equina syndrome: is the current management of patients presenting to
district general hospitals fit for purpose? A personal view based on a review of
the literature and a medicolegal experience.
AB - There is no universally agreed definition of cauda equina syndrome (CES).
Clinical signs of CES including direct rectal examination (DRE) do not reliably
correlate with cauda equina (CE) compression on MRI. Clinical assessment only
becomes reliable if there are symptoms/signs of late, often irreversible, CES.
The only reliable way of including or excluding CES is to perform MRI on all
patients with suspected CES. If the diagnosis is being considered, MRI should
ideally be performed locally in the District General Hospitals within one hour of
the question being raised irrespective of the hour or the day. Patients with
symptoms and signs of CES and MRI confirmed CE compression should be referred to
the local spinal service for emergency surgery. CES can be subdivided by the
degree of neurological deficit (bilateral radiculopathy, incomplete CES or CES
with retention of urine) and also by time to surgical treatment (12, 24, 48 or 72
hour). There is increasing understanding that damage to the cauda equina nerve
roots occurs in a continuous and progressive fashion which implies that there are
no safe time or deficit thresholds. Neurological deterioration can occur rapidly
and is often associated with longterm poor outcomes. It is not possible to
predict which patients with a large central disc prolapse compressing the CE
nerve roots are going to deteriorate neurologically nor how rapidly. Consensus
guidelines from the Society of British Neurological Surgeons and British
Association of Spinal Surgeons recommend decompressive surgery as soon as
practically possible which for many patients will be urgent/emergency surgery at
any hour of the day or night.
PMID- 26430016
TI - Outcome of lumbar spinal fusion surgery in obese patients: a systematic review
and meta-analysis.
AB - The aim of this study was to determine whether obesity affects pain, surgical and
functional outcomes following lumbar spinal fusion for low back pain (LBP). A
systematic literature review and meta-analysis was made of those studies that
compared the outcome of lumbar spinal fusion for LBP in obese and non-obese
patients. A total of 17 studies were included in the meta-analysis. There was no
difference in the pain and functional outcomes. Lumbar spinal fusion in the obese
patient resulted in a statistically significantly greater intra-operative blood
loss (weighted mean difference: 54.04 ml; 95% confidence interval (CI) 15.08 to
93.00; n = 112; p = 0.007) more complications (odds ratio: 1.91; 95% CI 1.68 to
2.18; n = 43858; p < 0.001) and longer duration of surgery (25.75 mins; 95% CI
15.61 to 35.90; n = 258; p < 0.001). Obese patients have greater intra-operative
blood loss, more complications and longer duration of surgery but pain and
functional outcome are similar to non-obese patients. Based on these results,
obesity is not a contraindication to lumbar spinal fusion.
PMID- 26430017
TI - Changes in cardiac function after pedicle subtraction osteotomy in patients with
a kyphosis due to ankylosing spondylitis.
AB - Cardiac disease in patients with ankylosing spondylitis (AS) has previously been
studied but not in patients with a kyphosis or in those who have undergone an
operation to correct it. The aim of this study was to measure the post-operative
changes in cardiac function of patients with an AS kyphosis after pedicle
subtraction osteotomy (PSO). The original cohort consisted of 39 patients (33
men, six women). Of these, four patients (two men, two women) were lost to follow
up leaving 35 patients (31 men, four women) to study. The mean age of the
remaining patients was 37.4 years (22.3 to 47.8) and their mean duration of AS
was 17.0 years (4.6 to 26.4). Echocardiographic measurements, resting heart rate
(RHR), physical function score (PFS), and full-length standing spinal radiographs
were obtained before surgery and at the two-year follow-up. The mean pre
operative RHR was 80.2 bpm (60.6 to 112.3) which dropped to a mean of 73.7 bpm
(60.7 to 90.6) at the two-year follow-up (p = 0.0000). Of 15 patients with normal
ventricular function pre-operatively, two developed mild left ventricular
diastolic dysfunction (LVDD) at the two-year follow-up. Of 20 patients with mild
LVDD pre-operatively only five had this post-operatively. Overall, 15 patients
had normal LV diastolic function before their operation and 28 patients had
normal LV function at the two-year follow-up. The clinical improvement was 15 out
of 20 (75.0%): cardiac function in patients with AS whose kyphosis was treated by
PSO was significantly improved.
PMID- 26430018
TI - Impact of lumbar instrumented circumferential fusion on the development of
adjacent vertebral compression fracture.
AB - We evaluated the impact of lumbar instrumented circumferential fusion on the
development of adjacent level vertebral compression fractures (VCFs).
Instrumented posterior lumbar interbody fusion (PLIF) has become a popular
procedure for degenerative lumbar spine disease. The immediate rigidity produced
by PLIF may cause more stress and lead to greater risk of adjacent VCFs. However,
few studies have investigated the relationship between PLIF and the development
of subsequent adjacent level VCFs. Between January 2005 and December 2009, a
total of 1936 patients were enrolled. Of these 224 patients had a new VCF and the
incidence was statistically analysed with other covariants. In total 150 (11.1%)
of 1348 patients developed new VCFs with PLIF, with 108 (72%) cases at adjacent
segment. Of 588 patients, 74 (12.5%) developed new subsequent VCFs with
conventional posterolateral fusion (PLF), with 37 (50%) patients at an adjacent
level. Short-segment fusion, female and age older than 65 years also increased
the development of new adjacent VCFs in patients undergoing PLIF. In the
osteoporotic patient, more rigid fusion and a higher stress gradient after PLIF
will cause a higher adjacent VCF rate.
PMID- 26430019
TI - Hexapod external fixator closed distraction in the management of stiff
hypertrophic tibial nonunions.
AB - Tibial nonunion represents a spectrum of conditions which are challenging to
treat, and optimal management remains unclear despite its high rate of incidence.
We present 44 consecutive patients with 46 stiff tibial nonunions, treated with
hexapod external fixators and distraction to achieve union and gradual deformity
correction. There were 31 men and 13 women with a mean age of 35 years (18 to 68)
and a mean follow-up of 12 months (6 to 40). No tibial osteotomies or bone graft
procedures were performed. Bony union was achieved after the initial surgery in
41 (89.1%) tibias. Four persistent nonunions united after repeat treatment with
closed hexapod distraction, resulting in bony union in 45 (97.8%) patients. The
mean time to union was 23 weeks (11 to 49). Leg-length was restored to within 1
cm of the contralateral side in all tibias. Mechanical alignment was restored to
within 5 degrees of normal in 42 (91.3%) tibias. Closed distraction of stiff
tibial nonunions can predictably lead to union without further surgery or bone
graft. In addition to generating the required distraction to achieve union,
hexapod circular external fixators can accurately correct concurrent deformities
and limb-length discrepancies.
PMID- 26430020
TI - Combined local and systemic antibiotic delivery improves eradication of wound
contamination: An animal experimental model of contaminated fracture.
AB - Systemic antibiotics reduce infection in open fractures. Local delivery of
antibiotics can provide higher doses to wounds without toxic systemic effects.
This study investigated the effect on infection of combining systemic with local
antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery. An
established Staphylococcus aureus contaminated fracture model in rats was used.
Wounds were debrided and irrigated six hours after contamination and animals
assigned to one of three groups, all of which received systemic antibiotics. One
group had local delivery via antibiotic gel, another PMMA beads and the control
group received no local antibiotics. After two weeks, bacterial levels were
quantified. Combined local and systemic antibiotics were superior to systemic
antibiotics alone at reducing the quantity of bacteria recoverable from each
group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the
bacterial counts between bead and gel delivery (p = 0.62). These results suggest
that local antibiotics augment the antimicrobial effect of systemic antibiotics.
Although no significant difference was found between vehicles, gel delivery
offers technical advantages with its biodegradable nature, ability to conform to
wound shape and to deliver increased doses. Further study is required to see if
the gel delivery system has a clinical role.
PMID- 26430021
TI - Slipped capital femoral epiphysis: is it worth the risk and cost not to offer
prophylactic fixation of the contralateral hip?
AB - Controversy remains whether the contralateral hip should be fixed in patients
presenting with unilateral slipped capital femoral epiphysis (SCFE). This
retrospective study compares the outcomes and cost of those patients who had
prophylactic fixation with those who did not. Between January 2000 and December
2010 a total of 50 patients underwent unilateral fixation and 36 had prophylactic
fixation of the contralateral hip. There were 54 males and 32 females with a mean
age of 12.3 years (9 to 16). The rate of a subsequent slip without prophylactic
fixation was 46%. The risk of complications was greater, the generic health
measures (Short Form-12 physical (p < 0.001) and mental (p = 0.004) summary
scores) were worse. Radiographic cam lesions in patients presenting with
unilateral SCFE were only seen in patients who did not have prophylactic
fixation. Furthermore, prophylactic fixation of the contralateral hip was found
to be a cost-effective procedure, with a cost per quality adjusted life year
gained of L1431 at the time of last follow-up. Prophylactic fixation of the
contralateral hip is a cost-effective operation that limits the morbidity from
the complications of a further slip, and the diminished functional outcome
associated with unilateral fixation.
PMID- 26430022
TI - The radiological assessment of pelvic obliquity in cerebral palsy and the impact
on hip development.
AB - Pelvic obliquity is a common finding in adolescents with cerebral palsy, however,
there is little agreement on its measurement or relationship with hip development
at different gross motor function classification system (GMFCS) levels. The
purpose of this investigation was to study these issues in a large, population
based cohort of adolescents with cerebral palsy at transition into adult
services. The cohort were a subset of a three year birth cohort (n = 98, 65M:
33F, with a mean age of 18.8 years (14.8 to 23.63) at their last radiological
review) with the common features of a migration percentage greater than 30% and a
history of adductor release surgery. Different radiological methods of measuring
pelvic obliquity were investigated in 40 patients and the angle between the
acetabular tear drops (ITDL) and the horizontal reference frame of the radiograph
was found to be reliable, with good face validity. This was selected for further
study in all 98 patients. The median pelvic obliquity was 4 degrees
(interquartile range 2 degrees to 8 degrees ). There was a strong correlation
between hip morphology and the presence of pelvic obliquity (effect of ITDL on
Sharpe's angle in the higher hip; rho 7.20 (5% confidence interval 5.59 to 8.81,
p < 0.001). This was particularly true in non-ambulant adolescents (GMFCS IV and
V) with severe pelvic obliquity, but was also easily detectable and clinically
relevant in ambulant adolescents with mild pelvic obliquity. The identification
of pelvic obliquity and its management deserves closer scrutiny in children and
adolescents with cerebral palsy.
PMID- 26430023
TI - Prediction of hip displacement in children with cerebral palsy: development of
the CPUP hip score.
AB - Hip displacement, defined in this study as a migration percentage (MP) of more
than 40%, is a common, debilitating complication of cerebral palsy (CP). In this
prospective study we analysed the risk of developing hip displacement within five
years of the first pelvic radiograph. All children with CP in southern and
western Sweden are invited to register in the hip surveillance programme CPUP.
Inclusion criteria for the two groups in this study were children from the CPUP
database born between 1994 and 2009 with Gross Motor Function Classification
System (GMFCS) III to V. Group 1 included children who developed hip
displacement, group 2 included children who did not develop hip displacement over
a minimum follow-up of five years. A total of 145 children were included with a
mean age at their initial pelvic radiograph of 3.5 years (0.6 to 9.7). The odds
ratio for hip displacement was calculated for GMFCS-level, age and initial MP and
head-shaft angle. A risk score was constructed with these variables using
multiple logistic regression analysis. The predictive ability of the risk score
was evaluated using the area under the receiver operating characteristics curve
(AUC). All variables had a significant effect on the risk of a MP > 40%. The
discriminatory accuracy of the CPUP hip score is high (AUC = 0.87), indicating a
high ability to differentiate between high- and low-risk individuals for hip
displacement. The CPUP hip score may be useful in deciding on further follow-up
and treatment in children with CP.
PMID- 26430024
TI - Draft Genome Sequence of Bacillus licheniformis S127, Isolated from a Sheep Udder
Clinical Infection.
AB - Bacillus licheniformis is a Gram-positive biofilm- and endospore-forming
bacterium, which contaminates dairy products and can be pathogenic to humans. The
draft genome sequencing for B. licheniformis strain S127 is reported here,
providing genetic data relevant to the ability of this strain to sustain its
survival in the dairy industry.
PMID- 26430025
TI - Genome Sequence of a Distinct Infectious Bursal Disease Virus.
AB - Infectious bursal disease virus is a relevant avian pathogen that affects poultry
production. Here, we report the full-length coding sequence of the Uruguayan
strain dIBDV/UY/2014/2202, isolated from a commercial broiler flock. The strain
belongs to the distinct IBDV lineage that is widely distributed in South America.
PMID- 26430026
TI - Genome Sequences of 64 Non-O157:H7 Shiga Toxin-Producing Escherichia coli
Strains.
AB - Shiga toxin-producing Escherichia coli (STEC) strains are human pathogens.
Although >400 non-O157 serotypes have been involved in human disease, whole
genome sequencing information is missing for many serotypes. We sequenced 64 STEC
strains comprising 38 serotypes, isolated from clinical sources, animals, and
environmental samples, to improve the phylogenetic understanding of these
important foodborne pathogens.
PMID- 26430027
TI - Draft Genome Sequences of Burkholderia pseudomallei and Staphylococcus aureus,
Isolated from a Patient with Chronic Rhinosinusitis.
AB - Here, we report the draft genome sequences of Burkholderia pseudomallei and
Staphylococcus aureus causing chronic rhinosinusitis. Whole-genome sequencing
determined the B. pseudomallei as sequence type (ST) 1381 and the S. aureus as
ST8. B. pseudomallei possessed the blaOXA-59 gene. This study illustrates the
potential emergence of B. pseudomallei in cases of chronic rhinosinusitis.
PMID- 26430028
TI - Complete Genome Sequences of Six South African Rabies Viruses.
AB - South African rabies viruses (RABVs) from dogs and jackals (canid viruses) are
highly related and most likely originated from a single progenitor. RABV is the
cause of most global human rabies cases. The complete genome sequences of 3 RABVs
from South Africa and Zimbabwe are reported here.
PMID- 26430029
TI - Draft Genome Sequences of 17 French Clostridium botulinum Group III Strains.
AB - Animal botulism is mainly associated with Clostridium botulinum group III strains
producing neurotoxin types C, C/D, D, and D/C. In this report, we present the
draft genome sequences of fourteen strains of Clostridium botulinum producing
type C/D and two strains producing type D/C isolated in France, and one strain
producing type D/C that originated from New Caledonia.
PMID- 26430030
TI - Mining Genomes of Three Marine Sponge-Associated Actinobacterial Isolates for
Secondary Metabolism.
AB - Here, we report the draft genome sequences of three actinobacterial isolates,
Micromonospora sp. RV43, Rubrobacter sp. RV113, and Nocardiopsis sp. RV163 that
had previously been isolated from Mediterranean sponges. The draft genomes were
analyzed for the presence of gene clusters indicative of secondary metabolism
using antiSMASH 3.0 and NapDos pipelines. Our findings demonstrated the chemical
richness of sponge-associated actinomycetes and the efficacy of genome mining in
exploring the genomic potential of sponge-derived actinomycetes.
PMID- 26430031
TI - Genome Sequence of Streptococcus agalactiae Strain H002, Serotype III, Isolated
in China from a Pregnant Woman.
AB - Here, we report the first whole-genome sequence of Streptococcus agalactiae
strain H002, serotype III, isolated in China from a woman 32 weeks pregnant. This
sequence represents an important addition to the published genomes and will
promote comparative genomic studies of S. agalactiae spp. isolated from diverse
regions, particularly when compared with Chinese strains.
PMID- 26430032
TI - Genome Sequencing of Ralstonia solanacearum Race 4, Biovar 4, and Phylotype I,
Strain YC45, Isolated from Rhizoma kaempferiae in Southern China.
AB - Ralstonia solanacearum is an important phytopathogen that attacks over 400 plant
species, including Zingiberaceae plants. Here, we report the complete genome
sequence of strain YC45, which was isolated from Rhizoma kaempferiae in southern
China.
PMID- 26430033
TI - Complete Genome Sequence of a Cyanotroph, Pseudomonas fluorescens NCIMB 11764,
Employing Single-Molecule Real-Time Technology.
AB - We report here the application of single-molecule real-time sequencing for
determining the entire genome structure of the cyanotroph Pseudomonas fluorescens
NCIMB 11764.
PMID- 26430034
TI - Draft Genome Sequence of the Strict Anaerobe Clostridium homopropionicum LuHBu1
(DSM 5847).
AB - Here, we report the draft genome sequence of Clostridium homopropionicum LuHBu1
(DSM 5847(T)), a strictly anaerobic bacterium, which performs propionate
fermentation and is capable of growing with 2-, 3-, or 4-hydroxybutyrate as its
sole substrate. The genome consists of a single chromosome of 3.65 Mb.
PMID- 26430035
TI - Correction for Sheflo et al., Complete Genome Sequences of Five Brevibacillus
laterosporus Bacteriophages.
PMID- 26430036
TI - Genome Sequence of Stachybotrys chartarum Strain 51-11.
AB - The Stachybotrys chartarum strain 51-11 genome was sequenced by shotgun
sequencing utilizing Illumina HiSeq 2000 and PacBio technologies. Since S.
chartarum has been implicated as having health impacts within water-damaged
buildings, any information extracted from the genomic sequence data relating to
toxins or the metabolism of the fungus might be useful.
PMID- 26430037
TI - Complete Genome Sequence of Noncytopathic Bovine Viral Diarrhea Virus 1
Contaminating a High-Passage RK-13 Cell Line.
AB - A high-passage rabbit kidney RK-13 cell line (HP-RK-13[KY], originally derived
from the ATCC CCL-37 cell line) used in certain laboratories worldwide is
contaminated with noncytopathic bovine viral diarrhea virus (ncpBVDV). On
complete genome sequence analysis, the virus strain was found to belong to BVDV
group 1b.
PMID- 26430038
TI - Complete Genome Sequence of Spiroplasma litorale TN-1T (DSM 21781), a Bacterium
Isolated from a Green-Eyed Horsefly (Tabanus nigrovittatus).
AB - Spiroplasma litorale TN-1(T) (DSM 21781) was isolated from the gut of a green
eyed horsefly (Tabanus nigrovittatus), collected at Ocracoke Island in North
Carolina in 1983. Here, we report the complete genome sequence of this bacterium
to facilitate the investigation of its biology.
PMID- 26430039
TI - Draft Genome Sequence of Erwinia billingiae OSU19-1, Isolated from a Pear Tree
Canker.
AB - Plant-associated Erwinia include pathogenic and nonpathogenic species. We report
the 5.6-Mb genome sequence of Erwinia billingiae OSU19-1, isolated from a canker
on a pear tree inoculated with Erwinia amylovora. OSU19-1 and a closely related
European isolate, E. billingiae Eb661(T), share many similarities including 40 kb
of plasmid sequence.
PMID- 26430040
TI - Genome Sequence of Antibiotic-Producing Bacillus amyloliquefaciens Strain KCTC
13012.
AB - We report the 4.0-Mb draft genome sequence of Bacillus amyloliquefaciens (syn.
Bacillus velezensis) KCTC 13012, which exhibits a broad spectrum of antagonistic
activity against bacteria and fungi and promotes plant growth as well. The genome
contains an array of biosynthetic gene clusters for secondary metabolites that
are comparable to those in Bacillus amyloliquefaciens subsp. plantarum FZB42(T).
PMID- 26430041
TI - Complete Genome Sequence of Rothia mucilaginosa Strain NUM-Rm6536, Isolated from
a Human Oral Cavity.
AB - Here, we present the complete genome sequence of Rothia mucilaginosa NUM-Rm6536,
a strain isolated from the tongue plaque of a healthy human adult. This strain is
amenable to genetic manipulation by transformation and so provides a useful
foundation for more detailed investigation of this species.
PMID- 26430042
TI - Complete Genome Sequence of Mycobacterium bovis Clinical Strain 1595, Isolated
from the Laryngopharyngeal Lymph Node of South Korean Cattle.
AB - Mycobacterium bovis strain 1595 was isolated from the lymph node of South Korean
native cattle. The complete genome sequence of strain 1595 was determined in 2
contigs and was found to be 4,351,712 bp in size, with a 65.64% G+C content and
4,358 predicted protein-coding genes.
PMID- 26430043
TI - Complete Genome Sequence of Xanthomonas arboricola pv. juglandis 417, a Copper
Resistant Strain Isolated from Juglans regia L.
AB - Here, we report the complete genome sequence of Xanthomonas arboricola pv.
juglandis 417, a copper-resistant strain isolated from a blighted walnut fruit
(Juglans regia L. cv. Chandler). The genome consists of a single chromosome
(5,218 kb).
PMID- 26430044
TI - Genome Comparison of an Ancestral Isolate and a Modern Isolate of Mycobacterium
tuberculosis of the Beijing Lineage from Sao Paulo, Brazil.
AB - Mycobacterium tuberculosis of the Bejing subtype (MtbB) is transmitted
efficiently in high burden countries for this genotype. A higher virulence was
associated with isolates of the "modern" Beijing genotype sub-lineages when
compared to "ancient" ones. Here, we report the full genomes of the strain
representing these two genotypes from Brazil, a country with a low incidence of
MtbB.
PMID- 26430045
TI - Complete Genome Sequence of Caulobacter crescentus Siphophage Seuss.
AB - Caulobacter crescentus is a water-dwelling bacterium known to have a dimorphic
life cycle. Here, we announce the complete genome of Seuss, a C. crescentus
icosahedral siphophage, and describe key features. Seuss is unique among phages
deposited in GenBank, with genes encoding novel hypothetical proteins composing
45% of its genome.
PMID- 26430046
TI - Complete Genome Sequence of Citrobacter freundii Myophage Merlin.
AB - Bacteriophage Merlin is a T4-like myophage which infects Citrobacter freundii, a
member of the Enterobacteriaceae family. C. freundii is an opportunistic pathogen
that is a common cause of nosocomial infections. This report announces the
complete genome of myophage Merlin and describes its features.
PMID- 26430047
TI - Complete Genome Sequence of Citrobacter freundii Myophage Michonne.
AB - Citrobacter freundii is a Gram-negative opportunistic pathogen that causes
dangerous infections such as neonatal meningitis. C. freundii also harbors
antibiotic resistance, making phages infecting this host valuable tools. Here, we
announce the complete genome of the C. freundii FelixO1-like myophage Michonne
and describe its notable features.
PMID- 26430048
TI - Complete Genome Sequence of Enterotoxigenic Escherichia coli Myophage Murica.
AB - Murica is an rv5-like myophage that infects enterotoxigenic Escherichia coli.
Pathogenic E. coli strains are responsible for many intestinal diseases, and
phages that infect these bacteria may prove useful in preventing severe health
issues. The following is a report of the complete genome sequence of Murica and
its important features.
PMID- 26430049
TI - Complete Genome Sequence of Carbapenemase-Producing Klebsiella pneumoniae
Myophage Matisse.
AB - Klebsiella pneumoniae is a leading cause of nosocomial infections in the United
States. Due to the emergence of multidrug-resistant strains, phages targeting K.
pneumoniae may be a useful alternative against this pathogen. Here, we announce
the complete genome of K. pneumoniae pseudo-T-even myophage Matisse and describe
its features.
PMID- 26430050
TI - Complete Genome Sequence of Klebsiella pneumoniae Carbapenemase-Producing K.
pneumoniae Myophage Miro.
AB - Klebsiella pneumoniae is a Gram-negative pathogen frequently associated with
antibiotic-resistant nosocomial infections. Bacteriophage therapy against K.
pneumoniae may be possible to combat these infections. The following describes
the complete genome sequence and key features of the pseudo-T-even K. pneumoniae
carbapenemase (KPC)-producing K. pneumoniae myophage Miro.
PMID- 26430051
TI - Draft Genome Sequences of Four Genetically Distinct Human Isolates of
Streptococcus dysgalactiae subsp. equisimilis.
AB - beta-Hemolytic group C and group G streptococci (GCS-GGS; Streptococcus
dysgalactiae subsp. equisimilis) emerged as human pathogens in the late 1970s. We
report here the draft genome sequences of four genetically distinct human strains
of GCS-GGS isolated between the 1960s and 1980s. Comparative analysis of these
genomes may provide a deeper understanding of GCS-GGS genome and virulence
evolution.
PMID- 26430052
TI - Complete Genome Sequences of Evolved Arsenate-Resistant Metallosphaera sedula
Strains.
AB - Metallosphaera sedula is a thermoacidophilic crenarchaeote with a 2.19-Mb genome.
Here, we report the genome sequences of several evolved derivatives of M. sedula
generated through adaptive laboratory evolution for enhanced arsenate resistance.
PMID- 26430053
TI - Draft Genome Sequence of a Heterotrophic Facultative Anaerobic Thermophilic
Bacterium, Ardenticatena maritima Strain 110ST.
AB - Ardenticatena maritima strain 110S(T) is a filamentous bacterium isolated from an
iron-rich coastal hydrothermal field, and it is a unique isolate capable of
dissimilatory iron or nitrate reduction among the members of the bacterial phylum
Chloroflexi. Here, we report the draft genome sequence comprising 3,569,367 bp,
containing 3,355 predicted coding sequences (CDSs).
PMID- 26430054
TI - Draft Genome Sequence of a Necrotoxigenic Escherichia coli Isolate.
AB - Here, we present the draft genome sequence of a necrotoxigenic Escherichia coli
strain isolated from a patient following a very rapidly evolving, lethal
necrotizing fasciitis.
PMID- 26430055
TI - Scotland is to scrap QOF, health minister announces.
PMID- 26430056
TI - The Degeneration of Meniscus Roots Is Accompanied by Fibrocartilage Formation,
Which May Precede Meniscus Root Tears in Osteoarthritic Knees.
AB - BACKGROUND: Fibrocartilage metaplasia in tendons and ligaments is an adaptation
to compression as well as a pathological feature during degeneration. Medial
meniscus posterior roots are unique ligaments that resist multidirectional
forces, including compression. PURPOSE: To characterize the degeneration of
medial meniscus posterior root tears in osteoarthritic knees, with an emphasis on
fibrocartilage and calcification. STUDY DESIGN: Cross-sectional study; Level of
evidence, 3. METHODS: Samples of medial meniscus posterior roots were harvested
from cadaveric specimens and patients during knee replacement surgery and grouped
as follows: normal reference, no tear, partial tear, and complete tear.
Degeneration was analyzed with histology, immunohistochemistry, and real-time
polymerase chain reaction. Uniaxial tensile tests were performed on specimens
with and without fibrocartilage. Quantifiable data were statistically analyzed by
the Kruskal-Wallis test with the Dunn comparison test. RESULTS: Thirty, 28, and
42 samples harvested from 99 patients were allocated into the no tear, partial
tear, and complete tear groups, respectively. Mean modified Bonar tendinopathy
scores for each group were 3.97, 9.31, and 14.15, respectively, showing a higher
degree of degeneration associated with the extent of the tear (P < .05 for all
groups). The characterization of root matrices revealed an increase in
fibrocartilage according to the extent of the tear. Tear margins revealed
fibrocartilage in 59.3% of partial tear samples and 76.2% of complete tear
samples, with a distinctive cleavage-like shape. Root tears with a similar shape
were induced within fibrocartilaginous areas during uniaxial tensile testing.
Even in the no tear group, 56.7% of samples showed fibrocartilage in the anterior
margin of the root, adjacent to the meniscus. An increased stained area of
calcification and expression of the ectonucleotide
pyrophosphatase/phosphodiesterase 1 gene were observed in the complete tear group
compared with the no tear group (P < .0001 and P = .24, respectively).
CONCLUSION: Fibrocartilage and calcification increased in medial meniscus
posterior roots, associated with the degree of the tear. Both findings, which
impair the ligament's resistance to tension, may play a pivotal role during the
pathogenesis of degenerative meniscus root tears in osteoarthritic knees.
Fibrocartilage and calcification may be useful as diagnostic markers as well as
markers of degeneration, which may aid in determining the treatment modality in
meniscus root tears. The presence of fibrocartilage in intact roots may suggest
an impending tear in osteoarthritic knees.
PMID- 26430057
TI - Clinical and Radiographic Predictors for Worsened Clinical Outcomes After Hip
Arthroscopic Labral Preservation and Capsular Closure in Developmental Dysplasia
of the Hip.
AB - BACKGROUND: Patients with developmental dysplasia of the hip (DDH) have a greater
risk of acetabular labral tearing and joint instability, which predispose them to
developing osteoarthritis. The arthroscopic management of DDH, however, remains
controversial. HYPOTHESIS: Specific clinical characteristics and radiographic
parameters correlate with and predict a worsened clinical outcome after hip
arthroscopic surgery for DDH. STUDY DESIGN: Case control study; Level of
evidence, 3. METHODS: Of patients with DDH who underwent an arthroscopic
procedure between March 2009 and June 2011, there were 28 hips in 28 patients (6
male and 22 female) that met the inclusion criteria. The mean patient age was
28.4 years. Clinical and radiographic follow-up evaluations up to a minimum of 2
years after surgery were performed for all patients. Failure of the procedure was
defined as conversion to subsequent surgery or having a Tonnis osteoarthritis
grade of 2 and modified Harris Hip Score (mHHS) that remained <85, and success
was defined as patients who did not need subsequent surgery and had an mHHS >85.
Univariate analysis and Cox hazard proportional analysis were performed on the 2
subpopulations. RESULTS: There were 9 patients in the failure group (including 3
hips with T nnis grade 2) and 19 patients in the success group. In 22 of 28
patients, the mean mHHS significantly improved from 61.6 +/- 18.8 (range, 12.0
85.0) preoperatively to 94.3 +/- 7.0 (range, 73.7-100.0) at final follow-up, and
the mean Non-Arthritic Hip Score (NAHS) improved from 56.2 +/- 13.9 (range, 35.0
81.3) preoperatively to 92.7 +/- 9.5 (range, 65.0-100.0) at final follow-up (P <
.001, Wilcoxon signed-rank test). Univariate analysis showed that a broken
Shenton line was significantly more prevalent in the failure group compared with
the success group (8/9 [89%] vs 3/19 [16%] patients, respectively; P < .001).
High-grade cartilage delamination (Multicenter Arthroscopy of the Hip Outcomes
Research Network [MAHORN] grades 3-5) was significantly higher in the failure
group than in the success group (8/9 [89%] vs 3/19 [16%] patients, respectively;
P < .001). The median femoral neck-shaft (FNS) angle in the failure group was
significantly higher than that in the success group (139 degrees vs 134 degrees
, respectively; P = .01). Further, Cox hazard proportional analysis of the
failure group showed that the predictors for a poor clinical outcome were the
presence of a broken Shenton line, FNS angle >140 degrees , center-edge (CE)
angle <19 degrees , body mass index (BMI) >23 kg/m(2), acetabular cartilage
damage (MAHORN grades 3-5), and cartilage damage of the femoral head
(International Cartilage Repair Society grades 2-4). The most important
predictors for a poor clinical outcome at the time of surgery were a broken
Shenton line and an FNS angle >140 degrees . CONCLUSION: Patients with a broken
Shenton line, FNS angle >140 degrees , CE angle <19 degrees , or BMI >23 kg/m(2)
at the time of surgery are not good candidates for the arthroscopic management of
DDH.
PMID- 26430058
TI - The Fate of Meniscus Tears Left In Situ at the Time of Anterior Cruciate Ligament
Reconstruction: A 6-Year Follow-up Study From the MOON Cohort.
AB - BACKGROUND: The management of meniscus tears identified at the time of primary
anterior cruciate ligament (ACL) reconstruction is highly variable and includes
repair, meniscectomy, and nontreatment. HYPOTHESIS/PURPOSE: The purpose of this
study was to determine the reoperation rate for meniscus tears left untreated at
the time of ACL reconstruction with a minimum follow-up of 6 years. The
hypothesis was that small peripheral tears identified at the time of ACL
reconstruction managed with "no treatment" would have successful clinical
outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients
with meniscus tears left untreated at the time of primary ACL reconstruction were
identified from a multicenter study group with a minimum 6-year follow-up.
Patient, tear, and reoperation data were obtained for analysis. The need for
reoperation was used as the primary endpoint, with analysis performed to
determine patient and tear characteristics associated with reoperation. RESULTS:
There were 194 patients with 208 meniscus tears (71 medial, 137 lateral) left in
situ without treatment with a complete follow-up for analysis. Of these, 97.8% of
lateral and 94.4% of medial untreated tears required no reoperation. Sixteen
tears (7.7%) left in situ without treatment underwent subsequent reoperation: 9
tears (4.3%) underwent reoperation in the setting of revision ACL reconstruction,
and 7 tears (3.4%) underwent reoperation for an isolated meniscus injury. The
patient age was significantly lower in patients requiring reoperation, while
tears measuring >=10 mm more frequently required reoperation. CONCLUSION: Lateral
and medial meniscus tears left in situ at the time of ACL reconstruction did not
require reoperation at a minimum 6-year follow-up for 97.8% and 94.4% of tears,
respectively. These findings re-emphasize the low reoperation rate after the
nontreatment of small, peripheral lateral meniscus tears while noting less
predictable results for medial meniscus tears left without treatment.
PMID- 26430059
TI - Processes Driving the Adaptive Radiation of a Tropical Tree (Diospyros,
Ebenaceae) in New Caledonia, a Biodiversity Hotspot.
AB - Due to its special geological history, the New Caledonian Archipelago is a mosaic
of soil types, and in combination with climatic conditions this results in a
heterogeneous environment across relatively small distances. A group of over 20
endemic species of Diospyros (Ebenaceae) has rapidly and recently radiated on the
archipelago after a single long-distance dispersal event. Most of the Diospyros
species in the radiating group are morphologically and ecologically well
differentiated, but they exhibit low levels of DNA variability. To investigate
the processes that shaped the diversification of this group we employed
restriction site associated DNA sequencing (RADseq). Over 8400 filtered SNPs
generally confirm species delimitations and produce a well-supported phylogenetic
tree. Our analyses document local introgression, but only a limited potential for
gene flow over longer distances. The phylogenetic relationships point to an early
regional clustering among populations and species, indicating that allopatric
speciation with respect to macrohabitat (i.e., climatic conditions) may have had
a role in the initial differentiation within the group. A later, more rapid
radiation involved divergence with respect to microhabitat (i.e., soil
preference). Several sister species in the group show a parallel divergence in
edaphic preference. Searches for genomic regions that are systematically
differentiated in this replicated phenotypic divergence pointed to loci
potentially involved in ion binding and cellular transport. These loci appear
meaningful in the context of adaptations to soil types that differ in heavy-metal
and mineral content. Identical nucleotide changes affected only two of these
loci, indicating that introgression may have played a limited role in their
evolution. Our results suggest that both allopatric diversification and
(parapatric) ecological divergence shaped successive rounds of speciation in the
Diospyros radiation on New Caledonia.
PMID- 26430060
TI - Rumbling Orchids: How To Assess Divergent Evolution Between Chloroplast
Endosymbionts and the Nuclear Host.
AB - Phylogenetic relationships inferred from multilocus organellar and nuclear DNA
data are often difficult to resolve because of evolutionary conflicts among gene
trees. However, conflicting or "outlier" associations (i.e., linked pairs of
"operational terminal units" in two phylogenies) among these data sets often
provide valuable information on evolutionary processes such as chloroplast
capture following hybridization, incomplete lineage sorting, and horizontal gene
transfer. Statistical tools that to date have been used in cophylogenetic studies
only also have the potential to test for the degree of topological congruence
between organellar and nuclear data sets and reliably detect outlier
associations. Two distance-based methods, namely ParaFit and Procrustean Approach
to Cophylogeny (PACo), were used in conjunction to detect those outliers
contributing to conflicting phylogenies independently derived from chloroplast
and nuclear sequence data. We explored their efficiency of retrieving outlier
associations, and the impact of input data (unit branch length and additive
trees) between data sets, by using several simulation approaches. To test their
performance using real data sets, we additionally inferred the phylogenetic
relationships within Neotropical Catasetinae (Epidendroideae, Orchidaceae), which
is a suitable group to investigate phylogenetic incongruence because of
hybridization processes between some of its constituent species. A comparison
between trees derived from chloroplast and nuclear sequence data reflected
strong, well-supported incongruence within Catasetum, Cycnoches, and Mormodes. As
a result, outliers among chloroplast and nuclear data sets, and in experimental
simulations, were successfully detected by PACo when using patristic distance
matrices obtained from phylograms, but not from unit branch length trees. The
performance of ParaFit was overall inferior compared to PACo, using either
phylograms or unit branch lengths as input data. Because workflows for applying
cophylogenetic analyses are not standardized yet, we provide a pipeline for
executing PACo and ParaFit as well as displaying outlier associations in plots
and trees by using the software R. The pipeline renders a method to identify
outliers with high reliability and to assess the combinability of the
independently derived data sets by means of statistical analyses.
PMID- 26430061
TI - Expression Divergence of Chemosensory Genes between Drosophila sechellia and Its
Sibling Species and Its Implications for Host Shift.
AB - Drosophila sechellia relies exclusively on the fruits of Morinda citrifolia,
which are toxic to most insects, including its sibling species Drosophila
melanogaster and Drosophila simulans. Although several odorant binding protein
(Obp) genes and olfactory receptor (Or) genes have been suggested to be
associated with the D. sechellia host shift, a broad view of how chemosensory
genes have contributed to this shift is still lacking. We therefore studied the
transcriptomes of antennae, the main organ responsible for detecting food
resource and oviposition, of D. sechellia and its two sibling species. We wanted
to know whether gene expression, particularly chemosensory genes, has diverged
between D. sechellia and its two sibling species. Using a very stringent
definition of differential gene expression, we found a higher percentage of
chemosensory genes differentially expressed in the D. sechellia lineage (7.8%)
than in the D. simulans lineage (5.4%); for upregulated chemosensory genes, the
percentages were 8.8% in D. sechellia and 5.2% in D. simulans. Interestingly,
Obp50a exhibited the highest upregulation, an approximately 100-fold increase,
and Or85c--previously reported to be a larva-specific gene--showed approximately
20-fold upregulation in D. sechellia. Furthermore, Ir84a (ionotropic receptor
84a), which has been proposed to be associated with male courtship behavior, was
significantly upregulated in D. sechellia. We also found expression divergence in
most of the chemosensory gene families between D. sechellia and the two sibling
species. Our observations suggest that the host shift of D. sechellia was
associated with the enrichment of differentially expressed, particularly
upregulated, chemosensory genes.
PMID- 26430064
TI - Physical activity across the life-span: Does feeling physically younger help you
to plan physical activities?
AB - We tested whether the relationship between subjective physical age and physical
activity is mediated by planning. Participants came from a broad age range (25-78
years, M = 39.57, standard deviation = 10.75) and reported relatively good health
( M = 3.36, standard deviation = 0.90). The model supported the suggested
mediation ( beta = -.01, standard error = .01, p = .042). Feeling physically
younger is associated with higher planning to adopt higher levels of physical
activity and more planning is associated with more subsequent physical activity.
Results open avenues for interventions that help people to become more active by
focusing on subjective age. One way to do so might be tailoring approaches for
interventions.
PMID- 26430062
TI - Recombining without Hotspots: A Comprehensive Evolutionary Portrait of
Recombination in Two Closely Related Species of Drosophila.
AB - Meiotic recombination rate varies across the genome within and between
individuals, populations, and species in virtually all taxa studied. In almost
every species, this variation takes the form of discrete recombination hotspots,
determined in some mammals by a protein called PRDM9. Hotspots and their
determinants have a profound effect on the genomic landscape, and share certain
features that extend across the tree of life. Drosophila, in contrast, are
anomalous in their absence of hotspots, PRDM9, and other species-specific
differences in the determination of recombination. To better understand the
evolution of meiosis and general patterns of recombination across diverse taxa,
we present a truly comprehensive portrait of recombination across time, combining
recently published cross-based contemporary recombination estimates from each of
two sister species with newly obtained linkage-disequilibrium-based historic
estimates of recombination from both of these species. Using Drosophila
pseudoobscura and Drosophila miranda as a model system, we compare recombination
rate between species at multiple scales, and we suggest that Drosophila replicate
the pattern seen in human-chimpanzee in which recombination rate is conserved at
broad scales. We also find evidence of a species-wide recombination modifier(s),
resulting in both a present and historic genome-wide elevation of recombination
rates in D. miranda, and identify broad scale effects on recombination from the
presence of an inversion. Finally, we reveal an unprecedented view of the
distribution of recombination in D. pseudoobscura, illustrating patterns of
linked selection and where recombination is taking place. Overall, by combining
these estimation approaches, we highlight key similarities and differences in
recombination between Drosophila and other organisms.
PMID- 26430063
TI - Single-cell RNA-seq reveals changes in cell cycle and differentiation programs
upon aging of hematopoietic stem cells.
AB - Both intrinsic cell state changes and variations in the composition of stem cell
populations have been implicated as contributors to aging. We used single-cell
RNA-seq to dissect variability in hematopoietic stem cell (HSC) and hematopoietic
progenitor cell populations from young and old mice from two strains. We found
that cell cycle dominates the variability within each population and that there
is a lower frequency of cells in the G1 phase among old compared with young long
term HSCs, suggesting that they traverse through G1 faster. Moreover,
transcriptional changes in HSCs during aging are inversely related to those upon
HSC differentiation, such that old short-term (ST) HSCs resemble young long-term
(LT-HSCs), suggesting that they exist in a less differentiated state. Our results
indicate both compositional changes and intrinsic, population-wide changes with
age and are consistent with a model where a relationship between cell cycle
progression and self-renewal versus differentiation of HSCs is affected by aging
and may contribute to the functional decline of old HSCs.
PMID- 26430065
TI - How Multidimensional Health Locus of Control predicts utilization of emergency
and inpatient hospital services.
AB - Health locus of control may be an important predictor of health care utilization.
We analyzed associations between health locus of control and frequency of
emergency department visits and hospital admissions, and investigated self-rated
health as a potential mediator. Overall, 863 patients in an urban emergency
department completed the Multidimensional Health Locus of Control instrument, and
self-reported emergency department use and hospital admissions in the last year.
We found small but significant associations between Multidimensional Health Locus
of Control and utilization, all of which were mediated by self-rated health. We
conclude that interventions to shift health locus of control may change patients'
perceptions of their own health, thereby impacting utilization.
PMID- 26430066
TI - Discerning the impact of personal and situational variables in risk perception of
coronary heart disease.
AB - Research into how people perceive risk has highlighted the interaction between
the available information and personal variables and their impact on judgement.
This study sought to identify demographic and health variables that influenced
risk and the influence of individual risk assessment, dispositional optimism and
negative affect on judgement. A total of 476 participants were asked to make
risks judgements of 24 vignettes depicting hypothetical risk scenarios. The
findings showed that while people are able to correctly recognise, in others,
relevant risk factors for coronary heart disease, risk perception is likely to
imply a personal consideration of the same risk factors in themselves.
PMID- 26430067
TI - Low sense of coherence during postoperative recovery is associated with a poorer
lumbar spinal stenosis - surgical outcome: A 5-year follow-up study.
AB - This study investigated the association between the 3-month postoperative sense
of coherence and the 5-year postoperative outcome of decompressive surgery for
lumbar spinal stenosis. The participants with a lower sense of coherence at the 3
month follow-up had a poorer functional ability and lower satisfaction with
surgery, higher pain ratings, lower life satisfaction and more depressive
symptoms 5 years postoperatively. A low 3-month sense of coherence associated
with greater pain and a poorer functional ability 5 years postoperatively.
Evaluating sense of coherence and depressive symptoms in patients who have had
lumbar spinal stenosis surgery may help in identifying those in need of enhanced
support for postoperative recovery.
PMID- 26430068
TI - Emotional management and quality of life in mother living versus multi-organ
donor renal transplant recipients.
AB - The aim of this study was to evaluate psychological differences and quality of
life between kidney recipients from living (mother) and multi-organ donor.
Overall, 40 patients who had undergone both living (mother) and multi-organ
kidney transplantation 3-6 months before were asked to complete four self-report
instruments: Toronto Alexithymia Scale, Short Form Health Survey, Regulatory
Emotional Self-efficacy, and Attachment Style Questionnaire. A greater difficulty
in emotional, social, and mental health functioning was found in recipients
receiving kidney from mother living donor. Moreover, in these patients, higher
levels of avoidant attachment dimensions were associated with a worse quality of
life.
PMID- 26430069
TI - Prevalence of burnout in Polish anesthesiologists and anesthetist nursing
professionals: A comparative non-randomized cross-sectional study.
AB - The purpose of the study was to assess the burnout levels in nurses ( N = 161)
versus physicians ( N = 373). The levels of burnout were evaluated by the Polish
adaptation of the Spanish Burnout Inventory (Cronbach's alpha > .70). High
burnout level was found in 18.63 percent nurses and 12.06 percent
anesthesiologists, and critical level in 3.74 percent nurses and 5.90 percent
anesthetists. There were statistically significant differences in Burnout global
score, Enthusiasm toward the job, Psychological exhaustion, and Indolence
subscales between nurses and physicians. No significant differences were found
between sexes in any variable.
PMID- 26430070
TI - Mass Spectrometry Selectivity, Specifically.
PMID- 26430071
TI - The Rise of Mass Spectrometry and the Fall of Edman Degradation.
PMID- 26430072
TI - Rapid Measurement of Cyclosporine and Sirolimus in Whole Blood by Paper Spray
Tandem Mass Spectrometry.
PMID- 26430073
TI - Clonotypic Light Chain Peptides Identified for Monitoring Minimal Residual
Disease in Multiple Myeloma without Bone Marrow Aspiration.
AB - BACKGROUND: Analytically sensitive techniques for measuring minimal residual
disease (MRD) in multiple myeloma (MM) currently require invasive and costly bone
marrow aspiration. These methods include immunohistochemistry (IHC), flow
cytometry, quantitative PCR, and next-generation sequencing. An ideal MM MRD test
would be a serum-based test sensitive enough to detect low concentrations of Ig
secreted from multifocal lesions. METHODS: Patient serum with abundant M-protein
before treatment was separated on a 1-dimensional SDS-PAGE gel, and the Ig light
chain (LC) band was excised, trypsin digested, and analyzed on a Q Exactive mass
spectrometer by LC-MS/MS. We used the peptide's abundance and sequence to
identify tryptic peptides that mapped to complementary determining regions of Ig
LCs. The clonotypic target tryptic peptides were used to monitor MRD in
subsequent serum samples with prior affinity enrichment. RESULTS: Sixty-two
patients were tested, 20 with no detectable disease by IHC and 42 with no
detectable disease by 6-color flow cytometry. A target peptide that could be
monitored was identified in 57 patients (91%). Of these 57, detectable disease by
LC-MS/MS was found in 52 (91%). CONCLUSIONS: The ability to use LC-MS/MS to
measure disease in patients who are negative by bone marrow-based methodologies
indicates that a serum-based approach has more analytical sensitivity and may be
useful for measuring deeper responses to MM treatment. The method requires no
bone marrow aspiration.
PMID- 26430074
TI - High-Resolution Mass Spectrometry for Characterizing the Metabolism of Synthetic
Cannabinoid THJ-018 and Its 5-Fluoro Analog THJ-2201 after Incubation in Human
Hepatocytes.
AB - BACKGROUND: Despite increasing prevalence of novel psychoactive substances, no
human metabolism data are currently available, complicating laboratory
documentation of intake in urine samples and assessment of the drugs'
pharmacodynamic, pharmacokinetic, and toxicological properties. In 2014, THJ-018
and THJ-2201, synthetic cannabinoid indazole analogs of JWH-018 and AM-2201, were
identified, with the National Forensic Laboratory Information System containing
220 THJ-2201 reports. Because of numerous adverse events, the Drug Enforcement
Administration listed THJ-2201 as Schedule I in January 2015. METHODS: We used
high-resolution mass spectrometry (HR-MS) (TripleTOF 5600(+)) to identify optimal
metabolite markers after incubating 10 MUmol/L THJ-018 and THJ-2201 in human
hepatocytes for 3 h. Data were acquired via full scan and information-dependent
acquisition triggered product ion scans with mass defect filter. In silico
metabolite predictions were performed with MetaSite and compared with metabolites
identified in human hepatocytes. RESULTS: Thirteen THJ-018 metabolites were
detected, with the major metabolic pathways being hydroxylation on the N-pentyl
chain and further oxidation or glucuronidation. For THJ-2201, 27 metabolites were
observed, predominantly oxidative defluorination plus subsequent carboxylation or
glucuronidation, and glucuronidation of hydroxylated metabolites. Dihydrodiol
formation on the naphthalene moiety was observed for both compounds. MetaSite
prediction matched well with THJ-018 hepatocyte metabolites but underestimated
THJ-2201 oxidative defluorination. CONCLUSIONS: With HR-MS for data acquisition
and processing, we characterized THJ-018 and THJ-2201 metabolism in human
hepatocytes and suggest appropriate markers for laboratories to identify THJ-018
and THJ-2201 intake and link observed adverse events to these new synthetic
cannabinoids.
PMID- 26430075
TI - CLSI C62-A: A New Standard for Clinical Mass Spectrometry.
PMID- 26430076
TI - First Steps toward Harmonization of LC-MS/MS Thyroglobulin Assays.
PMID- 26430077
TI - Multiplexed Quantification of Proglucagon-Derived Peptides by Immunoaffinity
Enrichment and Tandem Mass Spectrometry after a Meal Tolerance Test.
AB - BACKGROUND: Proglucagon-derived peptides (PGDPs), which include glucagon-like
peptide (GLP)-1, glucagon, and oxyntomodulin, are key regulators of glucose
homeostasis and satiety. These peptide hormones are typically measured with
immuno-based assays (e.g., ELISA, RIA), which often suffer from issues of
selectivity. METHODS: We developed a multiplexed assay for measuring PGDPs
including GLP-1 (7-36) amide, GLP-1 (9-36) amide, glucagon, and oxyntomodulin by
mass spectrometry and used this assay to examine the effect of a meal tolerance
test on circulating concentrations of these hormones. Participants fasted
overnight and were either given a meal (n = 8) or continued to fast (n = 4), with
multiple blood collections over the course of 3 h. Plasma samples were analyzed
by microflow immunoaffinity (IA)-LC-MS/MS with an isotope dilution strategy.
RESULTS: Assay performance characteristics were examined and established during
analytical validation for all peptides. Intra- and interassay imprecision were
found to be 2.2%-10.7% and 6.8%-22.5%, respectively. Spike recovery was >76%, and
dilution linearity was established up to a 16-fold dilution. Immediately after
the meal tolerance test, GLP-1 and oxyntomodulin concentrations increased and had
an almost identical temporal relationship, and glucagon concentrations increased
with a slight delay. CONCLUSIONS: IA-LC-MS/MS was used for the simultaneous and
selective measurement of PGDPs. This work includes the first indication of the
physiological concentrations and modulation of oxyntomodulin after a meal.
PMID- 26430079
TI - The Earth is no longer a square, the knee was never a hinge.
PMID- 26430078
TI - A Novel N-Tetrasaccharide in Patients with Congenital Disorders of Glycosylation,
Including Asparagine-Linked Glycosylation Protein 1, Phosphomannomutase 2, and
Mannose Phosphate Isomerase Deficiencies.
AB - BACKGROUND: Primary deficiencies in mannosylation of N-glycans are seen in a
majority of patients with congenital disorders of glycosylation (CDG). We report
the discovery of a series of novel N-glycans in sera, plasma, and cultured skin
fibroblasts from patients with CDG having deficient mannosylation. METHOD: We
used LC-MS/MS and MALDI-TOF-MS analysis to identify and quantify a novel N-linked
tetrasaccharide linked to the protein core, an N-tetrasaccharide
(Neu5Acalpha2,6Galbeta1,4-GlcNAcbeta1,4GlcNAc) in plasma, serum glycoproteins,
and a fibroblast lysate from patients with CDG caused by ALG1 [ALG1 (asparagine
linked glycosylation protein 1), chitobiosyldiphosphodolichol beta
mannosyltransferase], PMM2 (phosphomannomutase 2), and MPI (mannose phosphate
isomerase). RESULTS: Glycoproteins in sera, plasma, or cell lysate from ALG1-CDG,
PMM2-CDG, and MPI-CDG patients had substantially more N-tetrasaccharide than
unaffected controls. We observed a >80% decline in relative concentrations of the
N-tetrasaccharide in MPI-CDG plasma after mannose therapy in 1 patient and in
ALG1-CDG fibroblasts in vitro supplemented with mannose. CONCLUSIONS: This novel
N-tetrasaccharide could serve as a diagnostic marker of ALG1-, PMM2-, or MPI-CDG
for screening of these 3 common CDG subtypes that comprise >70% of CDG type I
patients. Its quantification by LC-MS/MS may be useful for monitoring therapeutic
efficacy of mannose. The discovery of these small N-glycans also indicates the
presence of an alternative pathway in N-glycosylation not recognized previously,
but its biological significance remains to be studied.
PMID- 26430080
TI - Unicompartmental knee arthroplasty: is the glass half full or half empty?
AB - There is a large amount of evidence available about the relative merits of
unicompartmental and total knee arthroplasty (UKA and TKA). Based on the same
evidence, different people draw different conclusions and as a result, there is
great variability in the usage of UKA. The revision rate of UKA is much higher
than TKA and so some surgeons conclude that UKA should not be performed. Other
surgeons believe that the main reason for the high revision rate is that UKA is
easy to revise and, therefore, the threshold for revision is low. They also
believe that UKA has many advantages over TKA such as a faster recovery, lower
morbidity and mortality and better function. They therefore conclude that UKA
should be undertaken whenever appropriate. The solution to this argument is to
minimise the revision rate of UKA, thereby addressing the main disadvantage of
UKA. The evidence suggests that this will be achieved if surgeons use UKA for at
least 20% of their knee arthroplasties and use implants that are appropriate for
these broad indications.
PMID- 26430081
TI - Long-term results of compartmental arthroplasties of the knee: Long term results
of partial knee arthroplasty.
AB - Partial knee arthroplasty (PKA), either medial or lateral unicompartmental knee
artroplasty (UKA) or patellofemoral arthroplasty (PFA) are a good option in
suitable patients and have the advantages of reduced operative trauma,
preservation of both cruciate ligaments and bone stock, and restoration of normal
kinematics within the knee joint. However, questions remain concerning long-term
survival. The goal of this review article was to present the long-term results of
medial and lateral UKA, PFA and combined compartmental arthroplasty for
multicompartmental disease. Medium- and long-term studies suggest reasonable
outcomes at ten years with survival greater than 95% in UKA performed for medial
osteoarthritis or osteonecrosis, and similarly for lateral UKA, particularly when
fixed-bearing implants are used. Disappointing long-term outcomes have been
observed with the first generation of patellofemoral implants, as well as early
Bi-Uni (i.e., combined medial and lateral UKA) or Bicompartmental (combined UKA
and PFA) implants due to design and fixation issues. Promising short- and med
term results with the newer generations of PFAs and bicompartmental
arthroplasties will require long-term confirmation.
PMID- 26430082
TI - Alignment and fixation in total knee arthroplasty: changing paradigms.
AB - Many aspects of total knee arthroplasty have changed since its inception. Modern
prosthetic design, better fixation techniques, improved polyethylene wear
characteristics and rehabilitation, have all contributed to a large change in
revision rates. Arthroplasty patients now expect longevity of their prostheses
and demand functional improvement to match. This has led to a re-examination of
the long-held belief that mechanical alignment is instrumental to a successful
outcome and a focus on restoring healthy joint kinematics. A combination of
kinematic restoration and uncemented, adaptable fixation may hold the key to
future advances.
PMID- 26430083
TI - The management of an infected total knee arthroplasty.
AB - Periprosthetic joint infection (PJI) is one of the most feared and challenging
complications following total knee arthroplasty. We provide a detailed
description of our current understanding regarding the management of PJI of the
knee, including diagnostic aids, pre-operative planning, surgical treatment, and
outcome.
PMID- 26430084
TI - The difficult primary total knee arthroplasty: a review.
AB - Primary total knee arthroplasty (TKA) is a reliable procedure with reproducible
long-term results. Nevertheless, there are conditions related to the type of
patient or local conditions of the knee that can make it a difficult procedure.
The most common scenarios that make it difficult are discussed in this review.
These include patients with many previous operations and incisions, and those
with severe coronal deformities, genu recurvatum, a stiff knee, extra-articular
deformities and those who have previously undergone osteotomy around the knee and
those with chronic dislocation of the patella. Each condition is analysed
according to the characteristics of the patient, the pre-operative planning and
the reported outcomes. When approaching the difficult primary TKA surgeons should
use a systematic approach, which begins with the review of the existing
literature for each specific clinical situation.
PMID- 26430085
TI - The constraints on day-case total knee arthroplasty: the fastest fast track.
AB - Total knee arthroplasty (TKA) is a major orthopaedic intervention. The length of
a patient's stay has been progressively reduced with the introduction of enhanced
recovery protocols: day-case surgery has become the ultimate challenge. This
narrative review shows the potential limitations of day-case TKA. These
constraints may be social, linked to patient's comorbidities, or due to surgery
related adverse events (e.g. pain, post-operative nausea and vomiting, etc.).
Using patient stratification, tailored surgical techniques and multimodal opioid
sparing analgesia, day-case TKA might be achievable in a limited group of
patients. The younger, male patient without comorbidities and with an excellent
social network around him might be a candidate. Demographic changes, effective
recovery programmes and less invasive surgical techniques such as unicondylar
knee arthroplasty, may increase the size of the group of potential day-case
patients. The cost reduction achieved by day-case TKA needs to be balanced
against any increase in morbidity and mortality and the cost of advanced follow
up at a distance with new technology. These factors need to be evaluated before
adopting this ultimate 'fast-track' approach.
PMID- 26430086
TI - Pain after total knee arthroplasty: a narrative review focusing on the
stratification of patients at risk for persistent pain.
AB - The patient with a painful arthritic knee awaiting total knee arthroplasty (TKA)
requires a multidisciplinary approach. Optimal control of acute post-operative
pain and the prevention of chronic persistent pain remains a challenge. The aim
of this paper is to evaluate whether stratification of patients can help identify
those who are at particular risk for severe acute or chronic pain. Intense acute
post-operative pain, which is itself a risk factor for chronic pain, is more
common in younger, obese female patients and those suffering from central pain
sensitisation. Pre-operative pain, in the knee or elsewhere in the body,
predisposes to central sensitisation. Pain due to osteoarthritis of the knee may
also trigger neuropathic pain and may be associated with chronic medication like
opioids, leading to a state of nociceptive sensitisation called 'opioid-induced
hyperalgesia'. Finally, genetic and personality related risk factors may also put
patients at a higher risk for the development of chronic pain. Those identified
as at risk for chronic pain would benefit from specific peri-operative management
including reduction in opioid intake pre-operatively, the peri-operative use of
antihyperalgesic drugs such as ketamine and gabapentinoids, and a close post
operative follow-up in a dedicated chronic pain clinic.
PMID- 26430087
TI - Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD
Progression.
AB - BACKGROUND AND OBJECTIVES: Common apolipoprotein L1 (APOL1) variants are
associated with increased risk of progressive CKD; however, not all individuals
with high-risk APOL1 variants experience CKD progression. Identification of
factors contributing to heterogeneity has important scientific and clinical
implications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using multivariable
Cox models, we analyzed data from 693 participants in the African American Study
of Kidney Disease and Hypertension to identify factors that modify the
association between APOL1 genotypes and CKD progression (doubling of serum
creatinine or incident ESRD). RESULTS: Participant mean age was 54 years old,
median GFR was 49 ml/min per 1.73 m(2), and 23% had the APOL1 high-risk genotype
(two copies of the high-risk allele). Over a mean follow-up of 7.8 years, 288
(42%) participants experienced CKD progression. As previously reported, the high
risk genotype was associated with higher risk of CKD progression compared with
the low-risk genotype (hazard ratio [HR], 1.88; 95% confidence interval [95% CI],
1.46 to 2.41). Although we found some suggestion that obesity (HR, 1.48; 95% CI,
1.05 to 2.08 and HR, 2.44; 95% CI, 1.66 to 3.57 for body mass index >= 30 versus
<30 kg/m(2); P interaction =0.04) and increased urinary excretion of urea
nitrogen (HR, 1.43; 95% CI, 0.98 to 2.09 versus HR, 2.33; 95% CI, 1.65 to 3.30
for urine urea nitrogen >= 8 versus <8 g/d; P interaction =0.04) were associated
with lower APOL1-associated risk for CKD progression, these findings were not
robust in sensitivity analyses with alternative cut points. No other
sociodemographic (e.g., education and income), clinical (e.g., systolic BP and
smoking), or laboratory (e.g., net endogenous acid production, urinary sodium and
potassium excretions, 25-hydroxy vitamin D, intact parathyroid hormone, or
fibroblast growth factor 23) variables modified the association between APOL1 and
CKD progression (P interaction >0.05 for each). CONCLUSIONS: Sociodemographic
factors and common risk factors for CKD progression do not seem to alter APOL1
related CKD progression. Additional investigation is needed to identify
nontraditional factors that may affect the association between APOL1 and
progressive CKD.
PMID- 26430089
TI - Long-Term Risk of Cancer in Survivors of Pediatric ESRD.
AB - BACKGROUND AND OBJECTIVES: ESRD is associated with an increased risk of
malignancies. We analyzed the incidence of cancer in patients with pediatric ESRD
after long-term follow-up. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All
Dutch patients born before 1979 who were transplanted at age <15 years old in
1972-1992 were followed until 2010. We explored type and incidence of
malignancies in patients compared with the general population using the National
Cancer Registry. RESULTS: After a median of 25.3 years (1.3-37.8) of
transplantation and at a median age of 33.5 years old (11.0-49.0), 105 primary
malignancies had occurred in 54 of 249 patients. Among them, cutaneous squamous
cell carcinoma was most frequent. Patients ages 25-30 years old had developed
16.5 times (95% confidence interval, 7.9 to 34.6) as many de novo tumors and 991
times (95% confidence interval, 313 to 3137) as many de novo cutaneous squamous
cell carcinomas as their general population counterparts; in survivors ages 45-50
years old, these numbers were 81.5 (95% confidence interval, 50.7 to 131.1) and
2610 (95% confidence interval, 1596 to 4267), respectively. Cumulative incidence
competing risk analysis showed that, after 30 years of transplantation, 41% of
the survivors had developed cancer; 31% had developed a second de novo cancer <1
year after initial cancer diagnosis. CONCLUSIONS: Cancer is highly prevalent
among patients with pediatric ESRD after 25.3 years of transplantation, with a
high rate of recurrence.
PMID- 26430090
TI - The promise of neurotechnology.
PMID- 26430088
TI - Risk Stratification for Rejection and Infection after Kidney Transplantation.
AB - BACKGROUND AND OBJECTIVES: Definition of individual risk profile is the first
step to implement strategies to keep the delicate balance between under- and
overimmunosuppression after kidney transplantation. DESIGN, SETTING,
PARTICIPANTS, & MEASUREMENTS: We used data from the Efficacy Limiting Toxicity
Elimination Symphony Study (1190 patients between 2002 and 2004) to model risk of
rejection and infection in the first year after kidney transplantation. External
validation was performed in a study population from the Fixed-Dose Concentration
Controlled Trial (630 patients between 2003 and 2006). RESULTS: Despite different
temporal dynamics, rejections and severe infections had similar overall
incidences in the first year after transplantation (23.4% and 25.5%,
respectively), and infections were the principal cause of death (43.2% of all
deaths). Recipient older age, deceased donor, higher number of HLA mismatches,
and high risk for cytomegalovirus disease were associated with infection;
deceased donor, higher number of HLA mismatches, and immunosuppressive therapy
including cyclosporin A (compared with tacrolimus), with rejection. These factors
were integrated into a two-dimensional risk stratification model, which defined
four risk groups: low risk for infection and rejection (30.8%), isolated risk for
rejection (36.1%), isolated risk for infection (7.0%), and high risk for
infection and rejection (26.1%). In internal validation, this model significantly
discriminated the subgroups in terms of composite end point (low risk for
infection/rejection, 24.4%; isolated risk for rejection and isolated risk for
infection, 31.3%; high risk for infection/rejection, 54.4%; P<0.001), rejection
episodes (isolated risk for infection and low risk for infection/rejection,
13.0%; isolated risk for rejection and high risk for infection/rejection, 24.2%;
P=0.001), and infection episodes (low risk for infection/rejection and isolated
risk for rejection, 12.0%; isolated risk for infection and high risk for
infection/rejection, 37.6%; P<0.001). External validation confirmed the
applicability of the model to an independent cohort. CONCLUSIONS: We propose a
two-dimensional risk stratification model able to disentangle the individual risk
for rejection and infection in the first year after kidney transplantation. This
concept can be applied to implement a personalized immunosuppressive and
antimicrobial treatment approach.
PMID- 26430093
TI - Q&A. Talking science and God with the pope's new astronomer.
PMID- 26430092
TI - BIOLOGY. New proteins may expand, improve genome editing.
PMID- 26430095
TI - PARTICLE PHYSICS. Have physicists seen the dying flash of dark matter?
PMID- 26430094
TI - BIOTECHNOLOGY. Europe's rifts over transgenic crops deepen at key deadline.
PMID- 26430096
TI - HYDRAULIC ENGINEERING. Holland's giant wavemaker has splashy debut.
PMID- 26430097
TI - The storm king.
PMID- 26430098
TI - How two pioneers took the tropics' pulse.
PMID- 26430099
TI - Pooling resources.
PMID- 26430102
TI - POLYMER CHEMISTRY. Safer fuels by integrating polymer theory into design.
PMID- 26430103
TI - STRUCTURAL BIOLOGY. Locking down the core of the pore.
PMID- 26430104
TI - CLIMATE CHANGE. The IPCC at a crossroads: Opportunities for reform.
PMID- 26430105
TI - CLIMATE CHANGE. Added value from IPCC approval sessions.
PMID- 26430106
TI - NEUROSCIENCE. A tree of the human brain.
PMID- 26430107
TI - ECOLOGY/PALEONTOLOGY. How stable are food webs during a mass extinction?
PMID- 26430108
TI - PLANETARY SCIENCE. Eyeing up a Jupiter-like exoplanet.
PMID- 26430109
TI - ATMOSPHERIC SCIENCE. Clouds resolved.
PMID- 26430110
TI - NEUROSCIENCE. It takes the world to understand the brain.
PMID- 26430111
TI - Slow or fast? A tale of synaptic vesicle recycling.
PMID- 26430112
TI - Brain crystals.
PMID- 26430113
TI - Dopamine and serotonin signals for reward across time scales.
PMID- 26430114
TI - End-bonded contacts for carbon nanotube transistors with low, size-independent
resistance.
AB - Moving beyond the limits of silicon transistors requires both a high-performance
channel and high-quality electrical contacts. Carbon nanotubes provide high
performance channels below 10 nanometers, but as with silicon, the increase in
contact resistance with decreasing size becomes a major performance roadblock. We
report a single-walled carbon nanotube (SWNT) transistor technology with an end
bonded contact scheme that leads to size-independent contact resistance to
overcome the scaling limits of conventional side-bonded or planar contact
schemes. A high-performance SWNT transistor was fabricated with a sub-10
nanometer contact length, showing a device resistance below 36 kilohms and on
current above 15 microampere per tube. The p-type end-bonded contact, formed
through the reaction of molybdenum with the SWNT to form carbide, also exhibited
no Schottky barrier. This strategy promises high-performance SWNT transistors,
enabling future ultimately scaled device technologies.
PMID- 26430115
TI - Megasupramolecules for safer, cleaner fuel by end association of long telechelic
polymers.
AB - We used statistical mechanics to design polymers that defy conventional wisdom by
self-assembling into "megasupramolecules" (>=5000 kg/mol) at low concentration
(<=0.3 weight percent). Theoretical treatment of the distribution of individual
subunits-end-functional polymers-among cyclic and linear supramolecules (ring
chain equilibrium) predicts that megasupramolecules can form at low total polymer
concentration if, and only if, the backbones are long (>400 kg/mol) and end
association strength is optimal. Viscometry and scattering measurements of long
telechelic polymers having polycyclooctadiene backbones and acid or amine end
groups verify the formation of megasupramolecules. They control misting and
reduce drag in the same manner as ultralong covalent polymers. With individual
building blocks short enough to avoid hydrodynamic chain scission (weight-average
molecular weights of 400 to 1000 kg/mol) and reversible linkages that protect
covalent bonds, these megasupramolecules overcome the obstacles of shear
degradation and engine incompatibility.
PMID- 26430116
TI - State shift in Deccan volcanism at the Cretaceous-Paleogene boundary, possibly
induced by impact.
AB - Bolide impact and flood volcanism compete as leading candidates for the cause of
terminal-Cretaceous mass extinctions. High-precision (40)Ar/(39)Ar data indicate
that these two mechanisms may be genetically related, and neither can be
considered in isolation. The existing Deccan Traps magmatic system underwent a
state shift approximately coincident with the Chicxulub impact and the terminal
Cretaceous mass extinctions, after which ~70% of the Traps' total volume was
extruded in more massive and more episodic eruptions. Initiation of this new
regime occurred within ~50,000 years of the impact, which is consistent with
transient effects of impact-induced seismic energy. Postextinction recovery of
marine ecosystems was probably suppressed until after the accelerated volcanism
waned.
PMID- 26430117
TI - Ultrafast 2D IR spectroscopy of the excess proton in liquid water.
AB - Despite decades of study, the structures adopted to accommodate an excess proton
in water and the mechanism by which they interconvert remain elusive. We used
ultrafast two-dimensional infrared (2D IR) spectroscopy to investigate protons in
aqueous hydrochloric acid solutions. By exciting O-H stretching vibrations and
detecting the spectral response throughout the mid-IR region, we observed the
interaction between the stretching and bending vibrations characteristic of the
flanking waters of the Zundel complex, [H(H2O)2](+), at 3200 and 1760 cm(-1),
respectively. From time-dependent shifts of the stretch-bend cross peak, we
determined a lower limit on the lifetime of this complex of 480 femtoseconds.
These results suggest a key role for the Zundel complex in aqueous proton
transfer.
PMID- 26430118
TI - Multiple repressive mechanisms in the hippocampus during memory formation.
AB - Memory stabilization after learning requires translational and transcriptional
regulations in the brain, yet the temporal molecular changes that occur after
learning have not been explored at the genomic scale. We used ribosome profiling
and RNA sequencing to quantify the translational status and transcript levels in
the mouse hippocampus after contextual fear conditioning. We revealed three types
of repressive regulations: translational suppression of ribosomal protein-coding
genes in the hippocampus, learning-induced early translational repression of
specific genes, and late persistent suppression of a subset of genes via
inhibition of estrogen receptor 1 (ESR1/ERalpha) signaling. In behavioral
analyses, overexpressing Nrsn1, one of the newly identified genes undergoing
rapid translational repression, or activating ESR1 in the hippocampus impaired
memory formation. Collectively, this study unveils the yet-unappreciated
importance of gene repression mechanisms for memory formation.
PMID- 26430119
TI - Holographic measurements of inhomogeneous cloud mixing at the centimeter scale.
AB - Optical properties and precipitation efficiency of atmospheric clouds are largely
determined by turbulent mixing with their environment. When cloud liquid water is
reduced upon mixing, droplets may evaporate uniformly across the population or,
in the other extreme, a subset of droplets may evaporate completely, leaving the
remaining drops unaffected. Here, we use airborne holographic imaging to
visualize the spatial structure and droplet size distribution at the smallest
turbulent scales, thereby observing their response to entrainment and mixing with
clear air. The measurements reveal that turbulent clouds are inhomogeneous, with
sharp transitions between cloud and clear air properties persisting to
dissipative scales (<1 centimeter). The local droplet size distribution
fluctuates strongly in number density but with a nearly unchanging mean droplet
diameter.
PMID- 26430120
TI - Community stability and selective extinction during the Permian-Triassic mass
extinction.
AB - The fossil record contains exemplars of extreme biodiversity crises. Here, we
examined the stability of terrestrial paleocommunities from South Africa during
Earth's most severe mass extinction, the Permian-Triassic. We show that stability
depended critically on functional diversity and patterns of guild interaction,
regardless of species richness. Paleocommunities exhibited less transient
instability-relative to model communities with alternative community organization
and significantly greater probabilities of being locally stable during the mass
extinction. Functional patterns that have evolved during an ecosystem's history
support significantly more stable communities than hypothetical alternatives.
PMID- 26430122
TI - Function of the nucleus accumbens in motor control during recovery after spinal
cord injury.
AB - Motivation facilitates recovery after neuronal damage, but its mechanism is
elusive. It is generally thought that the nucleus accumbens (NAc) regulates
motivation-driven effort but is not involved in the direct control of movement.
Using causality analysis, we identified the flow of activity from the NAc to the
sensorimotor cortex (SMC) during the recovery of dexterous finger movements after
spinal cord injury at the cervical level in macaque monkeys. Furthermore,
reversible pharmacological inactivation of the NAc during the early recovery
period diminished high-frequency oscillatory activity in the SMC, which was
accompanied by a transient deficit of amelioration in finger dexterity obtained
by rehabilitation. These results demonstrate that during recovery after spinal
damage, the NAc up-regulates the high-frequency activity of the SMC and is
directly involved in the control of finger movements.
PMID- 26430121
TI - Somatic mutation in single human neurons tracks developmental and transcriptional
history.
AB - Neurons live for decades in a postmitotic state, their genomes susceptible to DNA
damage. Here we survey the landscape of somatic single-nucleotide variants (SNVs)
in the human brain. We identified thousands of somatic SNVs by single-cell
sequencing of 36 neurons from the cerebral cortex of three normal individuals.
Unlike germline and cancer SNVs, which are often caused by errors in DNA
replication, neuronal mutations appear to reflect damage during active
transcription. Somatic mutations create nested lineage trees, allowing them to be
dated relative to developmental landmarks and revealing a polyclonal architecture
of the human cerebral cortex. Thus, somatic mutations in the brain represent a
durable and ongoing record of neuronal life history, from development through
postmitotic function.
PMID- 26430123
TI - Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain
dopaminergic neurons.
AB - Midbrain dopamine neurons are an essential component of the basal ganglia
circuitry, playing key roles in the control of fine movement and reward.
Recently, it has been demonstrated that gamma-aminobutyric acid (GABA), the chief
inhibitory neurotransmitter, is co-released by dopamine neurons. Here, we show
that GABA co-release in dopamine neurons does not use the conventional GABA
synthesizing enzymes, glutamate decarboxylases GAD65 and GAD67. Our experiments
reveal an evolutionarily conserved GABA synthesis pathway mediated by aldehyde
dehydrogenase 1a1 (ALDH1a1). Moreover, GABA co-release is modulated by ethanol
(EtOH) at concentrations seen in blood alcohol after binge drinking, and
diminished ALDH1a1 leads to enhanced alcohol consumption and preference. These
findings provide insights into the functional role of GABA co-release in midbrain
dopamine neurons, which may be essential for reward-based behavior and addiction.
PMID- 26430124
TI - After the bombs.
PMID- 26430125
TI - Erratum for the Report "A neoplastic gene fusion mimics trans-splicing of RNAs in
normal human cells" by H. Li, J. Wang, G. Mor, J. Sklar.
PMID- 26430126
TI - Erratum for the Report "Spreading depression triggers headache by activating
neuronal Panx1 channels" by H. Karatas, S. E. Erdener, Y. Gursoy-Ozdemir, S.
Lule, E. Eren-Kocak, Z. D. Sen, T. Dalkara.
PMID- 26430127
TI - Genetic determinants of in vivo fitness and diet responsiveness in multiple human
gut Bacteroides.
AB - Libraries of tens of thousands of transposon mutants generated from each of four
human gut Bacteroides strains, two representing the same species, were introduced
simultaneously into gnotobiotic mice together with 11 other wild-type strains to
generate a 15-member artificial human gut microbiota. Mice received one of two
distinct diets monotonously, or both in different ordered sequences. Quantifying
the abundance of mutants in different diet contexts allowed gene-level
characterization of fitness determinants, niche, stability, and resilience and
yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the
community. The approach described is generalizable and should be useful for
defining mechanisms critical for sustaining and/or approaches for deliberately
reconfiguring the highly adaptive and durable relationship between the human gut
microbiota and host in ways that promote wellness.
PMID- 26430130
TI - Surgical removal of failed ruptured Sinus of Valsalva Aneurysm device.
AB - A Sinus of Valsalva Aneurysm can cause aortic insufficiency, coronary artery flow
compromise, cardiac arrhythmia, or aneurysm rupture. There are different
management plans available, ranging from open surgery to percutaneous device
closure, but sometimes, device closure may be life-threatening. We report a case
of ruptured Sinus of Valsalva Aneurysm in a 42-year-old woman, which was managed
by percutaneous device closure that failed and required surgical removal of the
device.
PMID- 26430131
TI - Internal mammary artery with side-branch.
AB - We present the case of a 72-year-old man who underwent off-pump coronary artery
bypass grafting of 4 coronary arteries with exclusive use of the left internal
mammary artery with a side-branch (mediastinal artery). Before discharge from the
hospital, contrast computed tomography angiography confirmed the patency of all 4
coronary grafts. Use of the mediastinal artery side-branch of the internal
mammary artery allowed grafting of 4 coronary arteries using only one internal
thoracic artery.
PMID- 26430128
TI - Three methods of delivering clinic-based training on syndromic management of
sexually transmitted diseases in South Africa: a pilot study.
AB - INTRODUCTION: The South African National Department of Health sought to improve
syndromic management of sexually transmitted infections (STIs). Continuing
medical education on STIs was delivered at primary healthcare (PHC) clinics using
one of three training methods: (1) lecture, (2) computer and (3) paper-based.
Clinics with training were compared with control clinics. METHODS: Ten PHC
clinics were randomly assigned to control and 10 to each training method arm.
Clinicians participated in on-site training on six modules; two per week for
three weeks. Each clinic was visited by three or four unannounced standardised
patient (SP) actors pre-training and post-training. Male SPs reported symptoms of
male urethritis syndrome and female SPs reported symptoms of vaginal discharge
syndrome. Quality of healthcare was measured by whether or not clinicians
completed five tasks: HIV test, genital exam, correct medications, condoms and
partner notification. RESULTS: An average of 31% of clinicians from each PHC
attended each module. Quality of STI care was low. Pre-training (n=128)
clinicians completed an average of 1.63 tasks. Post-training (n=114) they
completed 1.73. There was no change in the number of STI tasks completed in the
control arm and an 11% increase overall in the training arms relative to the
control (ratio of relative risk (RRR)=1.11, 95% CI 0.67 to 1.84). Across training
arms, there was a 26% increase (RRR=1.26, 95% CI 0.77 to 2.06) associated with
lecture, 17% increase (RRR=1.17, 95% CI 0.59 to 2.28) with paper-based and 13%
decrease (RRR=0.87, 95% CI 0.40 to 1.90) with computer arm relative to the
control. CONCLUSIONS: Future interventions should address increasing training
attendance and computer-based training effectiveness. TRIAL REGISTRATION NUMBER:
AEARCTR-0000668.
PMID- 26430132
TI - Video-assisted thoracic surgery for cancer after thoracic aortic aneurysm repair.
AB - Video-assisted thoracoscopic surgery is increasingly accepted as an alternative
to open thoracotomy and has established efficacy in the management of non-small
cell lung cancer, but the presence of extensive intrapleural adhesions has been
considered a deterrent to a minimally invasive approach. We report the successful
use of video-assisted thoracoscopic surgery in 3 patients with history of open
thoracic aortic aneurysm repair who presented with left lower lobe stage I non
small-cell lung cancer. While this approach is feasible, it is technically
demanding and thus, at the present time, we recommend that its use be limited to
high-volume video-assisted thoracoscopic surgery centers.
PMID- 26430134
TI - The Shared Experience Help the Bereavement to Flow: A Family Support Group
Evaluation.
AB - When a family member dies, a bereavement period is taking place for all family
members. The death of a parent during childhood is a highly stressful event. This
study evaluates families' experiences of family support groups when a parent has
died. Families were participate in groups for children, teenagers, young adults,
and parents in seven sessions. The same topic which was discussed in all groups.
The support groups were evaluated qualitatively and quantitatively. The
participants were satisfied with the groups and experienced that the shared
experience facilitated bereavement to proceed. The results indicate that
families' experiences is being more open about feelings in their own family. A
support group can be one possibility to help the whole family in the bereavement.
PMID- 26430133
TI - Pediatric Primary Care Involvement in End-of-Life Care for Children.
AB - OBJECTIVES: To examine the relationship between pediatric primary care
involvement and hospice and home health care use at end of life. METHODS:
California Medicaid data were used to estimate the relationship between pediatric
primary care involvement and use of hospice and home health care using
generalized estimating equations. RESULTS: Of the 2037 children who died between
2007 and 2010, 11% used hospice and 23% used home health. Among all children,
primary care was not related to hospice use and was associated with home health
use, usual source of care (OR = 1.83, P < .05), comprehensive care (OR = 1.60, P
< .05), and continuous care (low: OR = 1.49, P < .05; moderate: OR = 2.57, P <
.05; high: OR = 2.12, P < .05). Primary care for children aged 15 to 20 years was
related to hospice use, usual source of care (OR = 4.06, P < .05) and continuous
care (low: OR = 4.92, P < .05; moderate OR = 4.09, P < .05; high OR = 3.92, P <
.05). Primary care for children under 5 years was associated with home health
use, usual source of care (OR = 2.59, P < .05), comprehensive care (OR = 2.49, P
< .05), and continuous care (low: OR = 2.22, P < .05; moderate: OR = 3.64, P <
.05; high: OR = 3.62, P < .05). For children aged 6 to 14 years, this association
was seen with continuous care (moderate: OR = 2.38, P < .05; high: OR = 2.13, P <
.05). Home health for children aged 15 to 20 years was related to continuous care
(moderate: OR = 2.32, P < .05). CONCLUSION: Primary care involvement affected
hospice use among older age-groups and home health use among younger age-groups.
These findings underscore the need for clinical knowledge about end-of-life care
for children of all ages among primary care providers.
PMID- 26430135
TI - Medical Students' Professionalism Narratives Reveal That Experiences With Death,
Dying, or Palliative Care Are More Positive Than Other Experiences During Their
Internal Medicine Clerkship.
AB - PURPOSE: More physicians need to acquire the skills of primary palliative care.
Medical students' clerkship experiences with death, dying, and palliative care
(DDPC), however, may create barriers to learning such skills during residency.
Whether professional development is differentially affected by DDPC is unknown.
This knowledge gap potentially hinders the development of educational strategies
to optimize students' preparedness for primary palliative care. METHOD: Third
year students submitted professionalism narratives (N = 4062) during their
internal medicine clerkship between 2004 and 2011. We identified DDPC-related
narratives and then randomly selected control narratives. Narratives were
compared by valence (positive or negative) and professionalism-related themes.
RESULTS AND CONCLUSION: Less than 10% of the narratives were related to DDPC, but
the majority was positive. There was a significant overlap in professionalism
themes between DDPC and control narratives. The results suggest student
preparedness for primary palliative care may be improved by addressing the common
professionalism challenges of clinical clerkships.
PMID- 26430137
TI - Mellon et al. Should All Deaf Children Learn Sign Language? Pediatrics.
2015;136(1):170-176.
PMID- 26430138
TI - Devore CD, Schutze GE; AAP, Council on School Health, Committee on Infectious
Dises. Head Lice. Pediatrics. 2015;135(5):e1355-1365.
PMID- 26430136
TI - Long-Term Outcomes and Causes of Death in Patients With Renovascular Disease
Undergoing Renal Artery Stenting.
AB - Renovascular disease (RVD) can lead to hypertension and chronic kidney disease
(CKD). Patients with advanced peripheral arterial disease (PAD) have a 5-year
mortality of ~30%. Rate and causes of death in patients with significant RVD, who
share similar risk factors with patients having PAD, are not well defined. We
assessed consecutive patients with RVD who underwent renal artery stenting at our
institution over 6 years. Specific causes of death were ascertained, and the
probability of survival was estimated. Cox models were fit to identify predictors
of outcomes. We identified 281 patients with RVD who underwent renal stenting.
Follow-up was available for all patients (median 5.1 years). All-cause mortality
was 24.2% at 5 years and 33.7% at 7 years (compounded annualized death rate:
5.5%). Of the 68 deaths, 36 (52.9%) were cardiovascular (13.2% acute myocardial
infarction, 13.2% stroke, 11.8% sudden death, and 10.3% congestive heart failure)
and 32 (47.1%) deaths had noncardiovascular causes. In patients with RVD
undergoing stenting, cardiovascular events are the most common causes of death.
Compared to patients with advanced PAD, RVD may have a lower 5-year mortality.
PMID- 26430139
TI - Campbell et al. Critical Elements in the Medical Evaluation of Suspected Child
Physical Abuse. Pediatrics. 2015;136(1):35-43.
PMID- 26430140
TI - Ralston SL, Lieberthal AS, Meissner HC, et al. Clinical Practice Guideline: The
Diagnosis, Management, and Prevention of Bronchiolitis. Pediatrics.
2014;134(5):e1474-e1502.
PMID- 26430141
TI - Kurowski et al. Online Problem-Solving Therapy for Executive Dysfuntion After
Child Traumatic Brain Injury. Pediatrics. 2013;132(1):e158-e166.
PMID- 26430143
TI - Risk of Misinterpretation and Limitation of the Diagnostic Accuracy.
PMID- 26430144
TI - Authors' Response.
PMID- 26430145
TI - 2015 SNMMI Highlights Lecture: Neurosciences.
PMID- 26430149
TI - A vision for ubiquitous sequencing.
AB - Genomics has recently celebrated reaching the $1000 genome milestone, making
affordable DNA sequencing a reality. With this goal successfully completed, the
next goal of the sequencing revolution can be sequencing sensors--miniaturized
sequencing devices that are manufactured for real-time applications and deployed
in large quantities at low costs. The first part of this manuscript envisions
applications that will benefit from moving the sequencers to the samples in a
range of domains. In the second part, the manuscript outlines the critical
barriers that need to be addressed in order to reach the goal of ubiquitous
sequencing sensors.
PMID- 26430150
TI - Biological data sciences in genome research.
AB - The last 20 years have been a remarkable era for biology and medicine. One of the
most significant achievements has been the sequencing of the first human genomes,
which has laid the foundation for profound insights into human genetics, the
intricacies of regulation and development, and the forces of evolution.
Incredibly, as we look into the future over the next 20 years, we see the very
real potential for sequencing more than 1 billion genomes, bringing even deeper
insight into human genetics as well as the genetics of millions of other species
on the planet. Realizing this great potential for medicine and biology, though,
will only be achieved through the integration and development of highly scalable
computational and quantitative approaches that can keep pace with the rapid
improvements to biotechnology. In this perspective, I aim to chart out these
future technologies, anticipate the major themes of research, and call out the
challenges ahead. One of the largest shifts will be in the training used to
prepare the class of 2035 for their highly interdisciplinary world.
PMID- 26430151
TI - Parlez-vous VUS?
AB - Human genome sequencing is routine and will soon be a staple in research and
clinical genetics. However, the promise of sequencing is often just that, with
genome data routinely failing to reveal useful insights about disease in general
or a person's health in particular. Nowhere is this chasm between promise and
progress more evident than in the designation, "variant of uncertain
significance" (VUS). Although it serves an important role, careful consideration
of VUS reveals it to be a nebulous description of genomic information and its
relationship to disease, symptomatic of our inability to make even crude
quantitative assertions about the disease risks conferred by many genetic
variants. In this perspective, I discuss the challenge of "variant
interpretation" and the value of comparative and functional genomic information
in meeting that challenge. Although already essential, genomic annotations will
become even more important as our analytical focus widens beyond coding exons.
Combined with more genotype and phenotype data, they will help facilitate more
quantitative and insightful assessments of the contributions of genetic variants
to disease.
PMID- 26430152
TI - Functional genomics bridges the gap between quantitative genetics and molecular
biology.
AB - Deep characterization of molecular function of genetic variants in the human
genome is becoming increasingly important for understanding genetic associations
to disease and for learning to read the regulatory code of the genome. In this
paper, I discuss how recent advances in both quantitative genetics and molecular
biology have contributed to understanding functional effects of genetic variants,
lessons learned from eQTL studies, and future challenges in this field.
PMID- 26430153
TI - Genomic approaches for understanding the genetics of complex disease.
AB - There are thousands of known associations between genetic variants and complex
human phenotypes, and the rate of novel discoveries is rapidly increasing.
Translating those associations into knowledge of disease mechanisms remains a
fundamental challenge because the associated variants are overwhelmingly in
noncoding regions of the genome where we have few guiding principles to predict
their function. Intersecting the compendium of identified genetic associations
with maps of regulatory activity across the human genome has revealed that
phenotype-associated variants are highly enriched in candidate regulatory
elements. Allele-specific analyses of gene regulation can further prioritize
variants that likely have a functional effect on disease mechanisms; and emerging
high-throughput assays to quantify the activity of candidate regulatory elements
are a promising next step in that direction. Together, these technologies have
created the ability to systematically and empirically test hypotheses about the
function of noncoding variants and haplotypes at the scale needed for
comprehensive and systematic follow-up of genetic association studies. Major
coordinated efforts to quantify regulatory mechanisms across genetically diverse
populations in increasingly realistic cell models would be highly beneficial to
realize that potential.
PMID- 26430155
TI - Linking RNA biology to lncRNAs.
AB - The regulatory potential of RNA has never ceased to amaze: from RNA catalysis, to
RNA-mediated splicing, to RNA-based silencing of an entire chromosome during
dosage compensation. More recently, thousands of long noncoding RNA (lncRNA)
transcripts have been identified, the majority with unknown function. Thus, it is
tempting to think that these lncRNAs represent a cadre of new factors that
function through ribonucleic mechanisms. Some evidence points to several lncRNAs
with tantalizing physiological contributions and thought-provoking molecular
modalities. However, dissecting the RNA biology of lncRNAs has been difficult,
and distinguishing the independent contributions of functional RNAs from
underlying DNA elements, or the local act of transcription, is challenging. Here,
we aim to survey the existing literature and highlight future approaches that
will be needed to link the RNA-based biology and mechanisms of lncRNAs in vitro
and in vivo.
PMID- 26430156
TI - Half dozen of one, six billion of the other: What can small- and large-scale
molecular systems biology learn from one another?
AB - Small-scale molecular systems biology, by which we mean the understanding of a
how a few parts work together to control a particular biological process, is
predicated on the assumption that cellular regulation is arranged in a circuit
like structure. Results from the omics revolution have upset this vision to
varying degrees by revealing a high degree of interconnectivity, making it
difficult to develop a simple, circuit-like understanding of regulatory
processes. We here outline the limitations of the small-scale systems biology
approach with examples from research into genetic algorithms, genetics,
transcriptional network analysis, and genomics. We also discuss the difficulties
associated with deriving true understanding from the analysis of large data sets
and propose that the development of new, intelligent, computational tools may
point to a way forward. Throughout, we intentionally oversimplify and talk about
things in which we have little expertise, and it is likely that many of our
arguments are wrong on one level or another. We do believe, however, that
developing a true understanding via molecular systems biology will require a
fundamental rethinking of our approach, and our goal is to provoke thought along
these lines.
PMID- 26430157
TI - The Mendelian disorders of the epigenetic machinery.
AB - The Mendelian disorders of the epigenetic machinery are genetic disorders that
involve disruption of the various components of the epigenetic machinery
(writers, erasers, readers, and remodelers) and are thus expected to have
widespread downstream epigenetic consequences. Studying this group may offer a
unique opportunity to learn about the role of epigenetics in health and disease.
Among these patients, neurological dysfunction and, in particular, intellectual
disability appears to be a common phenotype; however, this is often seen in
association with other more specific features in respective disorders. The
specificity of some of the clinical features raises the question whether specific
cell types are particularly sensitive to the loss of these factors. Most of these
disorders demonstrate dosage sensitivity as loss of a single allele appears to be
sufficient to cause the observed phenotypes. Although the pathogenic sequence is
unknown for most of these disorders, there are several examples where disrupted
expression of downstream target genes accounts for a substantial portion of the
phenotype; hence, it may be useful to systematically map such disease-relevant
target genes. Finally, two of these disorders (Rubinstein-Taybi and Kabuki
syndromes) have shown post-natal rescue of markers of the neurological
dysfunction with drugs that lead to histone deacetylase inhibition, indicating
that some of these disorders may be treatable causes of intellectual disability.
PMID- 26430154
TI - Enabling functional genomics with genome engineering.
AB - Advances in genome engineering technologies have made the precise control over
genome sequence and regulation possible across a variety of disciplines. These
tools can expand our understanding of fundamental biological processes and create
new opportunities for therapeutic designs. The rapid evolution of these methods
has also catalyzed a new era of genomics that includes multiple approaches to
functionally characterize and manipulate the regulation of genomic information.
Here, we review the recent advances of the most widely adopted genome engineering
platforms and their application to functional genomics. This includes engineered
zinc finger proteins, TALEs/TALENs, and the CRISPR/Cas9 system as nucleases for
genome editing, transcription factors for epigenome editing, and other emerging
applications. We also present current and potential future applications of these
tools, as well as their current limitations and areas for future advances.
PMID- 26430158
TI - Epigenomics and the structure of the living genome.
AB - Eukaryotic genomes are packaged into an extensively folded state known as
chromatin. Analysis of the structure of eukaryotic chromosomes has been
revolutionized by development of a suite of genome-wide measurement technologies,
collectively termed "epigenomics." We review major advances in epigenomic
analysis of eukaryotic genomes, covering aspects of genome folding at scales
ranging from whole chromosome folding down to nucleotide-resolution assays that
provide structural insights into protein-DNA interactions. We then briefly
outline several challenges remaining and highlight new developments such as
single-cell epigenomic assays that will help provide us with a high-resolution
structural understanding of eukaryotic genomes.
PMID- 26430159
TI - Defining cell types and states with single-cell genomics.
AB - A revolution in cellular measurement technology is under way: For the first time,
we have the ability to monitor global gene regulation in thousands of individual
cells in a single experiment. Such experiments will allow us to discover new cell
types and states and trace their developmental origins. They overcome fundamental
limitations inherent in measurements of bulk cell population that have frustrated
efforts to resolve cellular states. Single-cell genomics and proteomics enable
not only precise characterization of cell state, but also provide a stunningly
high-resolution view of transitions between states. These measurements may
finally make explicit the metaphor that C.H. Waddington posed nearly 60 years ago
to explain cellular plasticity: Cells are residents of a vast "landscape" of
possible states, over which they travel during development and in disease. Single
cell technology helps not only locate cells on this landscape, but illuminates
the molecular mechanisms that shape the landscape itself. However, single-cell
genomics is a field in its infancy, with many experimental and computational
advances needed to fully realize its full potential.
PMID- 26430160
TI - The first five years of single-cell cancer genomics and beyond.
AB - Single-cell sequencing (SCS) is a powerful new tool for investigating evolution
and diversity in cancer and understanding the role of rare cells in tumor
progression. These methods have begun to unravel key questions in cancer biology
that have been difficult to address with bulk tumor measurements. Over the past
five years, there has been extraordinary progress in technological developments
and research applications, but these efforts represent only the tip of the
iceberg. In the coming years, SCS will greatly improve our understanding of
invasion, metastasis, and therapy resistance during cancer progression. These
tools will also have direct translational applications in the clinic, in areas
such as early detection, noninvasive monitoring, and guiding targeted therapy. In
this perspective, I discuss the progress that has been made and the myriad of
unexplored applications that still lie ahead in cancer research and medicine.
PMID- 26430164
TI - 20 Years of Genome Research. Preface.
PMID- 26430161
TI - The path to routine use of genomic biomarkers in the cancer clinic.
AB - It has been almost 15 years since the first microarray-based studies creating
multigene biomarkers to subtype and predict survival of cancer patients. This
Perspective looks at why only a handful of genomic biomarkers have reached
clinical application and what advances are needed over the next 15 years to grow
this number. I discuss challenges in creating biomarkers and reproducing them at
the genomic and computational levels, including the problem of spatio-genomic
heterogeneity in an individual cancer. I then outline the challenges in
translating newly discovered genome-wide or regional events, like trinucleotide
mutation signatures, kataegis, and chromothripsis, into biomarkers, as well as
the importance of incorporating prior biological knowledge. Lastly, I outline the
practical problems of pharmaco-economics and adoption: Are new biomarkers viewed
as economically rational by potential funders? And if they are, how can their
results be communicated effectively to patients and their clinicians? Genomic
based diagnostics have immense potential for transforming the management of
cancer. The next 15 years will see a surge of research into the topics here that,
when combined with a stream of new targeted therapies being developed, will
personalize the cancer clinic.
PMID- 26430162
TI - The intersection of microbiome and host at the skin interface: genomic- and
metagenomic-based insights.
AB - The past two decades have been marked by a surge in research to understand the
microbial communities that live in association with the human body, in part
stimulated by affordable, high-throughput DNA sequencing technology. In the
context of the skin, this Perspective focuses on the current state of genomic-
and metagenomic-based host-microbe research and future challenges and
opportunities to move the field forward. These include elucidating nonbacterial
components of the skin microbiome (i.e., viruses); systematic studies to address
common perturbations to the skin microbiome (e.g., antimicrobial drugs, topical
cosmetic/hygienic products); improved approaches for identifying potential
microbial triggers for skin diseases, including species- and strain-level
resolution; and improved, clinically relevant models for studying the functional
and mechanistic roles of the skin microbiome. In the next 20 years, we can
realistically expect that our knowledge of the skin microbiome will inform the
clinical management and treatment of skin disorders through diagnostic tests to
stratify patient subsets and predict best treatment modality and outcomes and
through treatment strategies such as targeted manipulation or reconstitution of
microbial communities.
PMID- 26430163
TI - Signatures of post-zygotic structural genetic aberrations in the cells of
histologically normal breast tissue that can predispose to sporadic breast
cancer.
AB - Sporadic breast cancer (SBC) is a common disease without robust means of early
risk prediction in the population. We studied 282 females with SBC, focusing on
copy number aberrations in cancer-free breast tissue (uninvolved margin, UM)
outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were
studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same
patient as a control is the core of the study design. We identified 108 patients
with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy
number were the principal type of mutations in microscopically normal breast
cells, suggesting that oncogenic activation of genes via increased gene copy
number is a predominant mechanism for initiation of SBC pathogenesis. The gain of
ERBB2, with overexpression of HER2 protein, was the most common aberration in
normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R,
LIFR, and NGFR) also showed recurrent gains, and these were occasionally present
in combination with the gain of ERBB2. All the aberrations found in the normal
breast cells were previously described in cancer literature, suggesting their
causative, driving role in pathogenesis of SBC. We demonstrate that analysis of
normal cells from cancer patients leads to identification of signatures that may
increase risk of SBC and our results could influence the choice of surgical
intervention to remove all predisposing cells. Early detection of copy number
gains suggesting a predisposition toward cancer development, long before
detectable tumors are formed, is a key to the anticipated shift into a preventive
paradigm of personalized medicine for breast cancer.
PMID- 26430165
TI - Examination of Associations Among Three Distinct Subjective Aging Constructs and
Their Relevance for Predicting Developmental Correlates.
AB - Objectives: This study examined (a) the empirical associations among three
subjective aging (SA) constructs: felt age, attitudes toward own aging (ATOA),
and awareness of age-related change (AARC); (b) the moderating role of
chronological age in these associations; and (c) the predictive relevance of the
SA constructs with regard to two developmental correlates: functional health and
satisfaction with life. Method: Participants were 819 adults aged 40-98 years
from the United States and Germany. Parallel multiple mediation, moderated
mediation, and hierarchical regression analyses were used. Results: As
hypothesized, AARC mediated the association between the global measures of SA
(felt age and ATOA) and the developmental correlates. Specifically, more negative
global subjective aging predicted more AARC losses, which predicted poorer health
and well-being. Furthermore, this mediation pathway was moderated by
chronological age, such that, with increasing age, greater AARC was more strongly
related to poorer functional health (but not well-being). The multidimensional
measure, AARC, accounted for a significant amount of the variance in the
developmental correlates over and above the unidimensional SA constructs. A
consistent pattern emerged supporting the role of domain specificity and valence.
Discussion: These findings support the need for conceptualizing SA across
different behavioral domains and for distinguishing between positive and negative
SA.
PMID- 26430167
TI - Early Identification and Interventions for Autism Spectrum Disorder: Executive
Summary.
PMID- 26430168
TI - Early Identification of Autism Spectrum Disorder: Recommendations for Practice
and Research.
AB - Early identification of autism spectrum disorder (ASD) is essential to ensure
that children can access specialized evidence-based interventions that can help
to optimize long-term outcomes. Early identification also helps shorten the
stressful "diagnostic odyssey" that many families experience before diagnosis.
There have been important advances in research into the early development of
ASDs, incorporating prospective designs and new technologies aimed at more
precisely delineating the early emergence of ASD. Thus, an updated review of the
state of the science of early identification of ASD was needed to inform best
practice. These issues were the focus of a multidisciplinary panel of clinical
practitioners and researchers who completed a literature review and reached
consensus on current evidence addressing the question "What are the earliest
signs and symptoms of ASD in children aged <=24 months that can be used for early
identification?" Summary statements address current knowledge on early signs of
ASD, potential contributions and limitations of prospective research with high
risk infants, and priorities for promoting the incorporation of this knowledge
into clinical practice and future research.
PMID- 26430169
TI - Early Screening of Autism Spectrum Disorder: Recommendations for Practice and
Research.
AB - This article reviews current evidence for autism spectrum disorder (ASD)
screening based on peer-reviewed articles published to December 2013. Screening
provides a standardized process to ensure that children are systematically
monitored for early signs of ASD to promote earlier diagnosis. The current review
indicates that screening in children aged 18 to 24 months can assist in early
detection, consistent with current American Academy of Pediatrics'
recommendations. We identify ASD-specific and broadband screening tools that have
been evaluated in large community samples which show particular promise in terms
of accurate classification and clinical utility. We also suggest strategies to
help overcome challenges to implementing ASD screening in community practice, as
well as priorities for future research.
PMID- 26430170
TI - Early Intervention for Children With Autism Spectrum Disorder Under 3 Years of
Age: Recommendations for Practice and Research.
AB - This article reviews current evidence for autism spectrum disorder (ASD)
interventions for children aged <3 years, based on peer-reviewed articles
published up to December 2013. Several groups have adapted treatments initially
designed for older, preschool-aged children with ASD, integrating best practice
in behavioral teaching methods into a developmental framework based on current
scientific understanding of how infants and toddlers learn. The central role of
parents has been emphasized, and interventions are designed to incorporate
learning opportunities into everyday activities, capitalize on "teachable
moments," and facilitate the generalization of skills beyond the familiar home
setting. Our review identified several comprehensive and targeted treatment
models with evidence of clear benefits. Although some trials were limited to 8-
to 12-week outcome data, enhanced outcomes associated with some interventions
were evaluated over periods as long as 2 years. Based on this review,
recommendations are proposed for clinical practice and future research.
PMID- 26430171
TI - Incidence and risk factors of bleeding-related adverse events in patients with
chronic lymphocytic leukemia treated with ibrutinib.
AB - Ibrutinib is associated with bleeding-related adverse events of grade <= 2 in
severity, and infrequently with grade >= 3 events. To investigate the mechanisms
of bleeding and identify patients at risk, we prospectively assessed platelet
function and coagulation factors in our investigator-initiated trial of single
agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24
months we recorded grade <= 2 bleeding-related adverse events in 55% of 85
patients. No grade >= 3 events occurred. Median time to event was 49 days. The
cumulative incidence of an event plateaued by 6 months, suggesting that the risk
of bleeding decreases with continued therapy. At baseline, von Willebrand factor
and factor VIII levels were often high and normalized on treatment. Platelet
function measured via the platelet function analyzer (PFA-100TM) was impaired in
22 patients at baseline and in an additional 19 patients on ibrutinib (often
transiently). Collagen and adenosine diphosphate induced platelet aggregation was
tested using whole blood aggregometry. Compared to normal controls, response to
both agonists was decreased in all patients with chronic lymphocytic leukemia,
whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia
patients, response to collagen showed a mild further decrement on ibrutinib,
while response to adenosine diphosphate improved. All parameters associated with
a significantly increased risk of bleeding-related events were present at
baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower
levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR
3.73, P=0.0004). In conclusion, both disease and treatment-related factors
influence the risk of bleeding. Patients at greater risk for bleeding of grade <=
2 can be identified by clinical laboratory tests and counseled to avoid aspirin,
non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov
identifier NCT01500733.
PMID- 26430172
TI - Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association
retrospective study.
AB - Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from
classical Hodgkin lymphoma. We conducted a retrospective study to investigate the
management of patients with nodular lymphocyte predominant Hodgkin lymphoma.
Clinical characteristics, treatment and outcome of adult patients with nodular
lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study
Association centers. Progression-free survival (PFS) and overall survival (OS)
were analyzed, and the competing risks formulation of a Cox regression model was
used to control the effect of risk factors on relapse or death as competing
events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte
predominant Hodgkin lymphoma. Initial management consisted in watchful waiting
(36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno
chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus
rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS
estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6%
after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or
immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole
population, early treatment with chemotherapy or radiotherapy, but not rituximab
alone (Hazard ratio 0.695 [0.320-1.512], P=0.3593) significantly reduced the risk
of progression compared to watchful waiting (HR 0.388 [0.234-0.643], P=0.0002).
Early treatment appears more beneficial compared to watchful waiting in terms of
progression-free survival, but has no impact on overall survival. Radiotherapy in
selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and
combined modality treatment, chemotherapy or immuno-chemotherapy for other
patients, are the main options to treat adult patients with a curative intent.
PMID- 26430174
TI - A 'Healthy Islands' framework for climate change in the Pacific.
AB - Small Pacific Island countries (PICs) are among the most vulnerable countries in
the world to the anticipated detrimental health effects of climate change. The
assessment of health vulnerabilities and planning adaptation strategies to
minimize the impacts of climate change on health tests traditional health
governance structures and depends on strong linkages and partnerships between
actors involved in these vital processes. This article reviews the actors,
processes and contexts of the climate change and health vulnerability assessment
and adaptation planning project carried out by the World Health Organization and
health sector partners in three island countries in the Micronesian region of the
Pacific throughout 2010 and 2011: Federated States of Micronesia, Marshall
Islands and Palau. Despite their shared history and cultural characteristics, the
findings and implications of this article are considered to have substantial
relevance and potential application to other PICs. The modified 'Healthy Islands'
framework for climate change and health adaptation presented in this article
draws upon real-world experience and governance theory from both the health and
climate change literature and, for the first time, places health systems
adaptation within the vision for 'Healthy Islands' in the Pacific region.
PMID- 26430175
TI - Retail therapy.
PMID- 26430173
TI - Red blood cell alloimmunization is influenced by the delay between Toll-like
receptor agonist injection and transfusion.
AB - Murine models of red blood cell transfusion show that inflammation associated
with viruses or methylated DNA promotes red blood cell alloimmunization. In
vaccination studies, the intensity of antigen-specific responses depends on the
delay between antigen and adjuvant administration, with a short delay limiting
immune responses. In mouse models of alloimmunization, the delay between the
injection of Toll-like receptor agonists and transfusion is usually short. In
this study, we hypothesized that the timing of Toll-like receptor 3 agonist
administration affects red blood cell alloimmunization. Poly(I:C), a Toll-like
receptor 3 agonist, was administered to B10BR mice at various time points before
the transfusion of HEL-expressing red blood cells. For each time point, we
measured the activation of splenic HEL-presenting dendritic cells, HEL-specific
CD4(+) T cells and anti-HEL antibodies in serum. The phenotype of activated
immune cells depended on the delay between transfusion and Toll-like receptor
dependent inflammation. The production of anti-HEL antibodies was highest when
transfusion occurred 7 days after agonist injection. The proportion of HEL
presenting CD8alpha(+) dendritic cells producing interleukin-12 was highest in
mice injected with poly(I:C) 3 days before transfusion. Although the number of
early-induced HEL-specific CD4(+) T cells was similar between groups, a high
proportion of these cells expressed CD134, CD40 and CD44 in mice injected with
poly(I:C) 7 days before transfusion. This study clearly shows that the delay
between transfusion and Toll-like receptor-induced inflammation influences the
immune response to transfused red blood cells.
PMID- 26430176
TI - 'Part of the problem, part of the solution' - adult physicians' role in
adolescent and young adult health.
PMID- 26430177
TI - Establishing an infrastructure to support the development and delivery of
clinical research in patients with kidney disease.
AB - The UK Kidney Research Consortium (UKKRC) was established in 2007 to promote
clinical research in adults and children affected by kidney disease. Clinical
study groups (CSGs) are the core subgroups of UKKRC. The aim of the CSGs is to
generate a portfolio of clinical studies that can and should be undertaken in the
UK. Since 2007 the CSGs have helped develop and secure funding for 13 studies to
a total value of L13443648. Funders include Kidney Research UK, Medical Research
Council, British Heart Foundation and National Institute of Health Research
(NIHR). The studies address the full translational pathway. UKKRC is thus a
unique structure that dovetails with the NIHR Renal Disorders Specialty Group to
generate and deliver a portfolio of high-quality renal studies.
PMID- 26430178
TI - Transcatheter aortic valve implantation - what the general physician needs to
know.
AB - With an increasingly elderly population, the incidence of aortic stenosis (AS) is
rising. While surgical aortic valve replacement remains the gold standard
treatment for patients with severe symptomatic AS, transcatheter aortic valve
implantation (TAVI) has emerged as the treatment of choice for patients who are
inoperable or high surgical risk. TAVI has been shown to be associated with a
clear mortality benefit when compared with medical therapy and to be at least as
good as surgical aortic valve replacement in this patient group. The last few
years have seen rapid development in this revolutionary technology in conjunction
with increasing centre and operator experience, and indications for the procedure
are swiftly expanding. In this review, we summarise the current evidence base and
discuss factors that need to be considered by the general physician when
contemplating TAVI as a treatment option, including practical aspects, emerging
indications and future directions.
PMID- 26430179
TI - Improving the management of spontaneous bacterial peritonitis in cirrhotic
patients: assessment of an intervention in trainee doctors.
AB - Spontaneous bacterial peritonitis (SBP) in cirrhotic patients is a serious
complication associated with a high mortality rate. A baseline audit of the acute
medical take (AMT) at Northwick Park suggested a lack of awareness regarding
management. A questionnaire based on contemporary SBP guidelines was circulated
to all trainee doctors (FY1 to SpR). Ascitic fluid testing requests were analysed
over a six-month period. The electronic requesting system was updated to include
prompts and direct links to Trust SBP guidelines, and a one-hour lecture to all
members of the AMT, supported by an educational booklet on SBP, was performed. Re
audit was carried out six months post-intervention, the AMT completed a second
questionnaire and ascitic fluid testing requests were re-audited. In comparable
pre- and post-intervention AMT cohorts, a clinical and educational intervention
led to a significant improvement in understanding of when to investigate
(p<=0.001), samples (p = 0.002) and containers (p<=0.001) required, urgency of
obtaining results (p<=0.001), and initiation of treatment for suspected SBP (p =
0.007). Significantly more ascitic samples were sent, with specific suspicion of
SBP more readily documented, crucial to expediting laboratory processing.
Targeted education and production of a clinical algorithm has significantly
improved the management of patients with SBP.
PMID- 26430180
TI - Recognition and management of acute kidney injury in hospitalised patients can be
partially improved with the use of a care bundle.
AB - Acute kidney injury (AKI) is common in hospitalised patients but is known be
suboptimally managed; the National Confidential Enquiry into Patient Outcomes and
Death (NCEPOD) report in 2009 identified significant failings in AKI care. An
audit, using standards suggested by the NCEPOD report, of all adult inpatients
with AKI in a large central-London NHS hospital in a 7-day period in 2011 showed
poor recognition and management of AKI. In response, an AKI 'care bundle' was
developed and deployed throughout the hospital along with a programme of enhanced
education. Re-audit in 2013 showed that AKI was significantly more likely to have
been recognised by the clinical team than in 2011, and patients with AKI were
significantly more likely to have had fluid status clinically assessed and
nephrotoxic medication stopped in 2013 than in 2011. There was no significant
improvement in fluid administration if assessed as hypovolaemic and compliance
with the guideline for prevention of contrast nephropathy. In 2011, all audit
measures were met in 3.7% of patient-days versus 8.4% in 2013. More in-depth work
is necessary to better understand the factors which limit optimal care.
PMID- 26430181
TI - Experience from two decades of the Cambridge Rapid Access Neurology Clinic.
AB - We report on the evolution of the rapid access neurology clinic (established in
1995) at Addenbrooke's Hospital, Cambridge. Annualised attendance data
demonstrate an ever increasing demand, with primary headache disorders now
accounting for more than 40% of referrals. Secondary causes of headache
(including intracranial tumours, idiopathic intracranial hypertension, carotid or
vertebral artery dissection and subdural haematomas) remain infrequent. In all
such cases, there were additional diagnostic clues. The number of patients
referred with problems related to chronic neurological diseases has fallen
considerably, reflecting the roles of specialist nurses and clinics. Imaging
investigation of choice shifted from computerised tomography scan (45 to 16%)
towards magnetic resonance imaging (17 to 47%). Management is increasingly on an
outpatient basis, often without the need for a follow-up appointment. The
experience presented here should inform further development of rapid access
neurology clinics across the UK and suggests the need for acute headache
services, in line with those for transient ischaemic attack and first seizure.
PMID- 26430182
TI - Management of cardiovascular conditions in a cohort of patients with HIV:
experience from a joint HIV/cardiology clinic.
AB - The aim of this study was to assess cardiovascular diagnoses and management in a
cohort of patients diagnosed with HIV, and the performance of a joint
HIV/Cardiology Clinic in a tertiary hospital setting. A retrospective analysis
was performed on all patients referred to a joint HIV/Cardiology Clinic at our
hospital. Data on 120 patients were collected. In this predominantly male
population (male 101 and female 19) coronary artery disease (CAD) was the most
common diagnosis (34%, n = 41). Other diseases included hypertension (12.5%, n =
15), cardiomyopathy (12.5%, n = 15) and arrhythmia (6%, n = 8). The majority of
remaining cases included non-cardiac chest pain and palpitations. In addition to
usual primary and secondary preventive measures for CAD, complex procedures, such
as percutaneous coronary intervention, cardiac resynchronisation therapy for left
ventricular systolic dysfunction and radiofrequency ablation for arrhythmias,
were carried out. Overall cardiovascular mortality among the group was 2.5% (n =
3) over 4 years. The results indicate the efficacy of a specialist joint
HIV/Cardiology Clinic in diagnosing and managing various cardiac conditions in a
complex cohort of patients with HIV.
PMID- 26430183
TI - Sexual health issues in adolescents and young adults.
AB - Adolescence is a time of sexual risk-taking and experimentation but also
vulnerability. Young people may present to general physicians with systemic
symptoms of sexually transmitted infections (STIs), such as arthritis, hepatitis
or rash, but may not necessarily volunteer information about sexual activity. It
is important for physicians to ask directly about sexual risks and if appropriate
test for STIs and pregnancy. Knowing how to take a sexual history and consent a
patient for an HIV test are core medical skills that all physicians should be
trained to competently perform. Safeguarding young people is the responsibility
of all healthcare professionals who come into contact with them, and young
victims of abuse may present with physical symptoms such as abdominal pain or
deliberate self-harm. We must all be aware of indicators of both child sexual
exploitation and HIV infection and not be afraid to ask potentially awkward
questions. If we don't we may miss vital opportunities to prevent or minimise
harm to young people.
PMID- 26430184
TI - Drug therapies in severe asthma - the era of stratified medicine.
AB - Difficult-to-treat asthma affects up to 20% of patients with asthma and is
associated with significant healthcare cost. It is an umbrella term that defines
a heterogeneous clinical problem including incorrect diagnosis, comorbid
conditions and treatment non-adherence; when these are effectively addressed,
good symptom control is frequently achieved. However, in 3-5% of adults with
difficult-to-treat asthma, the problem is severe disease that is unresponsive to
currently available treatments. Current treatment guidelines advise the
'stepwise' increase of corticosteroids, but it is now recognised that many
aspects of asthma are not corticosteroid responsive, and that this 'one size fits
all' approach does not deliver clinical benefit in many patients and can also
lead to side effects. The future of management of severe asthma will involve
optimisation with currently available treatments, particularly corticosteroids,
including addressing non-adherence and defining an 'optimised' corticosteroid
dose, allied with the use of 'add-on' target-specific novel treatments. This
review examines the current status of novel treatments and research efforts to
identify novel targets in the era of stratified medicines in severe asthma.
PMID- 26430185
TI - Tackling emerging infections: clinical and public health lessons from the West
African Ebola virus disease outbreak, 2014-2015.
AB - The magnitude of the 2014-2015 West African Ebola virus disease outbreak was
unforeseen at its onset and the initial international response was slow. The high
mortality and the panic that this outbreak induced had a major effect on health
systems. In this article we discuss some of the key public health and clinical
lessons from this Ebola outbreak, including combining epidemiology, modelling and
anthropology, and the initial evidence for the importance of fluid and antibiotic
management.
PMID- 26430186
TI - Stroke rehabilitation: long-term rehabilitation after stroke.
AB - Many stroke survivors, despite improvements in mortality and morbidity, remain
dependent on others for everyday activities. People with stroke need access to
effective specialist multidisciplinary rehabilitation services that are organised
and integrated within the whole system of health and social care. They also
commonly come under the care of generalists in various clinical contexts,
including intercurrent illness. This Clinical Medicine Concise Guideline
abstracts key recommendations from the National Institute for Health and Care
Excellence Clinical Guideline 162 on stroke rehabilitation of particular
relevance to clinicians in general medicine, to inform their front-line practice
and promote liaison and collaboration with the specialist service.
PMID- 26430187
TI - Diabetes in older people.
AB - The management of diabetes in older people is often challenging and poorly
researched. The prevalence of cognitive impairment, chronic kidney disease and
other co-existing comorbidities increase with age and have a significant impact
on glycaemic control targets and treatment options. This conference examined
current clinical practice, highlighted differences in the management of diabetes
in the older person and suggested potential areas of future research.
PMID- 26430188
TI - Acute liver failure.
AB - Acute liver failure (ALF) is a rare critical illness with high mortality whose
successful management requires early recognition and effective initial
management. Though it may result from a wide variety of causes, in the UK and
much of the developed world most cases result from paracetamol-induced
hepatotoxicity, and administration of antidotal N-acetyl cysteine at first
recognition is key. Involvement of local critical care services should occur at
an early stage for stabilisation, monitoring and supportive care with parallel
discussion with specialist liver centres to identify those patients who may
benefit from transfer. Prognostic criteria are applied to identify patients for
emergency liver transplantation, and candidates for surgery are prioritised on
waitlisting schemes. Outcomes now approach that of elective surgery. However, the
majority of cases, and particularly those with paracetamol-induced disease,
recover with supportive medical care alone. Overall outcomes for patients with
ALF have improved dramatically over the last three decades, but mortality remains
unacceptable and further advances in care are required.
PMID- 26430189
TI - Management of acute severe ulcerative colitis (NICE CG 166).
AB - Ulcerative colitis (UC) presents as an acute severe flare in 10-15% of new cases
and it occurs in 15% of patients with established disease. Acute severe UC can
lead to significant morbidity and mortality in predominantly younger patients
without other comorbidities. Inpatient hospital admission and a multidisciplinary
approach are vital in appropriate and timely management. Important but simple
aspects in the initial work-up and treatment of such patients are frequently
overlooked during the acute medical take. An overview of the general and more
specialist management of this important presentation are discussed herein.
PMID- 26430190
TI - Acute oesophageal symptoms.
AB - Acute oesophageal symptoms include acute dysphagia or food bolus impaction (most
commonly due to strictures, Schatzki ring and eosinophilic oesophagitis), acute
chest pain with odynophagia due to oesophageal infections, motility disorders and
acute oesophageal rupture (of which oesophageal intramural haematoma is a
subtype). Acute full thickness oesophageal rupture carries a high mortality if
not recognised early; the clinical features and conditions with which this may be
confused are presented and discussed.
PMID- 26430191
TI - Acute upper gastrointestinal bleeding.
AB - Acute upper gastrointestinal bleeding (AUGIB) is a frequently encountered medical
emergency with an incidence of 84-160/100000 and associated with mortality of
approximately 10%. Guidelines from the National Institute for Care and Care
Excellence outline key features in the management of AUGIB. Patients require
prompt resuscitation and risk assessment using validated tools. Upper
gastrointestinal endoscopy provides accurate diagnosis, aids in estimating
prognosis and allows therapeutic intervention. Endoscopy should be undertaken
immediately after resuscitation in unstable patients and within 24 hours in all
other patients. Interventional radiology may be required for bleeding
unresponsive to endoscopic intervention. Drug therapy depends on the cause of
bleeding. Intravenous proton pump inhibitors should be used in patients with high
risk ulcers. Terlipressin and broad-spectrum antibiotics should be used following
variceal haemorrhage. Hospitals admitting patients with AUGIB need to provide
well organised services and ensure access to relevant services for all patients,
and particularly to out of hours endoscopy.
PMID- 26430192
TI - Acute alcohol toxicity and withdrawal in the emergency room and medical
admissions unit.
AB - Alcohol-related hospital attendances and admissions continue to escalate despite
a fall in alcohol consumption levels in the UK population overall. People with
alcohol-related problems pose a significant and often disproportionate burden on
acute medical services as their management is often complex and challenging. This
article focuses on the management of alcohol intoxication, with particular
emphasis on aggressive and possibly violent behaviour; alcohol withdrawal;
fitting; and the prevention and treatment of Wernicke's encephalopathy.
PMID- 26430194
TI - Lesson of the month 1: A cough that doesn't fit the mould.
AB - Aspergillus disease has a wide spectrum of manifestations within the lungs;
however invasive Aspergillus is most commonly associated with immunocompromise or
pre-existing respiratory disease. Here we present a case of Aspergillus
tracheobronchitis causing right middle lobe collapse, masquerading as late-onset
asthma in a patient with no pre-existing risk factors following massive
inhalation of Aspergillus spores from working with compost. This case highlights
the importance of having a high index of suspicion for Aspergillus-related
disease even in those with no traditional risk factors.
PMID- 26430195
TI - Lesson of the month 2: An unusual presentation of hyperinsulinaemic hypoglycaemia
with possible underlying diagnosis of glucose-sensitive insulinoma or islet cell
hyperplasia.
AB - Postprandial hypoglycaemia can occur in islet cell hyperplasia and in reactive
hypoglycaemia. Less commonly, it can occur with insulinoma. A case is described
where the differential diagnosis was glucose-sensitive insulinoma or islet cell
hyperplasia. Typical provocation was prolonged exertion or fasting followed by
ingestion of sugary snacks resulting in hypoglycaemic seizures and collapse.
Biochemistry and computerised tomography imaging were consistent with an
insulinoma in the pancreatic tail, but this was not confirmed on endoscopic
ultrasound. Selective intra-arterial calcium stimulation with hepatic venous
sampling results suggested a diagnosis of islet cell hyperplasia. Ten years
later, repeat imaging was consistent with a neuroendocrine tumour. Surgical
resection has resulted in remission of symptoms. The patient will be monitored
long term to ensure no recurrence.
PMID- 26430196
TI - Image of the month: Chest pain after cocaine use.
PMID- 26430197
TI - Letters to the editor.
PMID- 26430198
TI - Letters to the editor.
PMID- 26430199
TI - Impact of stroke services on geriatric medicine in Wales.
PMID- 26430200
TI - On-going lessons in fluid prescription: assessment of adherence to weight-based
intravenous fluid prescribing in medical inpatients.
PMID- 26430202
TI - Meeting report--9th IRIC International Symposium on Molecular Targets in Cancer
Genomics.
AB - Graduate students and postdoctoral fellows at the Institute for Research in
Immunology and Cancer (IRIC) organized the 9th IRIC International Symposium on 14
15 May, 2015. The symposium was held at the IRIC, an ultra-modern research hub
and training center located on the hilltop of the Universite de Montreal campus
in Montreal, Canada. This year's title was 'Molecular Targets in Cancer
Genomics', reflecting the common interest of the IRIC student community. Through
four broadly themed sessions, organizers sought to highlight the new generation
of anti-cancer strategies including targeted therapies directed against
actionable cancer-specific mutations, and immunotherapies, which enhance immune
responses against cancer. Both targeted and immunotherapies are tailored to
cancer-specific features, and require precise knowledge of cancer cells, from
their genome to their proteome. The focus of this symposium was on translating
the molecular basis of cancer into a functional understanding of aberrant
pathways, and to uncover novel targets to be exploited for cancer therapeutic
strategies.
PMID- 26430203
TI - Ingested and Aspirated Foreign Bodies.
AB - Esophageal and aspirated foreign bodies have important clinical significance, and
both should be considered carefully when the history or physical examination
findings raise sufficient suspicion. The published evidence regarding the
diagnosis and management of foreign body ingestion or aspiration is weighted
disproportionately with observational studies, case controls, expert opinion, and
systematic reviews. Most of the publications would receive a categorization of C
(observational studies including case-control and cohort design) and D (expert
opinion, case reports, and clinical reasoning). One of the few prospective
studies examining the diagnostic evaluation of foreign body aspiration in
children could be considered level B evidence (randomized clinical trials,
systematic reviews, or diagnostic studies with minor limitations). This study
found that the medical history is the most important predictive part of the
evaluation. There is evidence for considering bronchoscopy if there is
significant history suggestive of foreign body aspiration, even in the setting of
normal physical examination findings. (28). Most ingested foreign bodies
spontaneously pass without incident. However, special attention should be paid to
objects in the esophagus as well as to batteries and magnets. Based on a
systematic review of the literature (level B evidence) and the potential for
rapid and life-threatening damage, batteries in the esophagus should be removed
immediately. (10) Other objects, such as coins, may be observed for passage in an
asymptomatic patient. In addition, given the high risk of significant
complications, ingestion of high-powered magnets should be quickly and carefully
evaluated. Although single magnets are likely to pass without complication,
multiple magnets or magnets ingested with other metal objects can cause
significant damage and should be removed if there is any concern for mural
entrapment, bowel perforation, or failure to progress. (10)(16)(17)(18)(19).
Lastly, another systematic review of the literature (level B evidence) about the
aspiration of food objects in children suggests that this is a significant public
health concern with potentially devastating consequences. Despite clear
legislation and regulation by the Consumer Product Safety Commission regarding
toys, there is no similar regulation of high-risk foods. The data suggest that
there is opportunity for improvement in legislation about the production and
packaging of high-risk items as well as in the education of caregivers. (22)
PMID- 26430204
TI - Return to Play.
AB - Based primarily on consensus and some research evidence, young athletes with
musculoskeletal and cervical spine injuries should not return to play until they
have full range of motion, resolution of pain, normal strength, psychological
readiness, and the ability to demonstrate adequate sport-specific skills. Based
primarily on consensus, young athletes with suspected concussion should not
return to sport until they have returned to their baseline physical and cognitive
activities and successfully completed a return-to-play protocol. Based on
consensus and some research evidence, any young athlete with a significant eye
injury, visual changes, or abnormal findings on ophthalmologic examination
results should not return to play until evaluated by an ophthalmologist. A
significant number of eye injuries can be prevented by the use of approved
protective eyewear.
PMID- 26430205
TI - Patient Safety and Quality Improvement: Reducing Risk of Harm.
AB - Most medical errors and preventable adverse events represent failures of complex
systems. Pediatric clinicians must ensure a safe environment for health-care
delivery to children. To do so, they must recognize risk factors for errors and
adverse events; ensure effective communication with patients, parents, and
colleagues; heighten situation awareness; develop high-functioning, high
reliability teams; implement and employ technology carefully; and provide
integrated, ongoing education to trainees.
PMID- 26430206
TI - Case 1: Hepatomegaly and Growth Failure in an 11-year-old Girl With Type 1
Diabetes.
PMID- 26430207
TI - Case 2: Ankle Pain, Swelling, and Fever after Trauma in a 15-year-old Boy.
PMID- 26430208
TI - Case 3: Acute Onset of Headache, Fever, and Right Arm Weakness in 12-year-old
Boy.
PMID- 26430209
TI - Corrections.
PMID- 26430210
TI - Complementary, Holistic, and Integrative Medicine: Yoga.
PMID- 26430211
TI - Visual Diagnosis: A 7-Month-Old Girl With Cyanotic Spells.
AB - Infants can develop acquired methemoglobinemia due to intake of well water high
in nitrate concentrations. Although methemoglobinemia usually presents with more
severe symptoms, this diagnosis should be considered in an infant with
intermittent cyanosis in the absence of underlying heart or lung disease. Well
water should be avoided in infancy unless properly tested.
PMID- 26430212
TI - Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome
maturation.
AB - Rab GTPases control membrane identity, fusion and transport by interaction with
effector proteins. Effectors that influence the activation-inactivation cycle of
their own or other Rab proteins contribute to the timely conversion of Rab
membrane identities. Rab5 and its effector rabaptin5 (Rbpt5, also known as
RABEP1) are generally considered the prime example for a positive-feedback loop
in which Rab5-GTP recruits Rbpt5 in complex with Rabex5 (also known as RABGEF1),
the GDP/GTP exchange factor of Rab5, to early endosomes, thus maintaining the
Rab5 membrane identity. By deletion analysis, we found that the membrane
recruitment of Rabaptin5 required binding to Rab4 and Rabex5, but not Rab5.
Deletion of either one of the two Rab5-binding domains or silencing of Rab5
expression did not affect Rabaptin5 recruitment, but produced giant endosomes
with early and late endosomal characteristics. The results contradict the model
of feedback activation of Rab5 and instead indicate that Rbpt5 is recruited by
both Rabex5 recognizing ubiquitylated cargo and by Rab4 to activate Rab5 in a
feed-forward manner.
PMID- 26430213
TI - Regulation of polycystin-1 ciliary trafficking by motifs at its C-terminus and
polycystin-2 but not by cleavage at the GPS site.
AB - Failure to localize membrane proteins to the primary cilium causes a group of
diseases collectively named ciliopathies. Polycystin-1 (PC1, also known as PKD1)
is a large ciliary membrane protein defective in autosomal dominant polycystic
kidney disease (ADPKD). Here, we developed a large set of PC1 expression
constructs and identified multiple sequences, including a coiled-coil motif in
the C-terminal tail of PC1, regulating full-length PC1 trafficking to the primary
cilium. Ciliary trafficking of wild-type and mutant PC1 depends on the dose of
polycystin-2 (PC2, also known as PKD2), and the formation of a PC1-PC2 complex.
Modulation of the ciliary trafficking module mediated by the VxP ciliary
targeting sequence and Arf4 and Asap1 does not affect the ciliary localization of
full-length PC1. PC1 also promotes PC2 ciliary trafficking. PC2 mutations
truncating its C-terminal tail but not those changing the VxP sequence to AxA or
impairing the pore of the channel, leading to a dead channel, affect PC1 ciliary
trafficking. Cleavage at the GPCR proteolytic site (GPS) of PC1 is not required
for PC1 trafficking to cilia. We propose a mutually dependent model for the
ciliary trafficking of PC1 and PC2, and that PC1 ciliary trafficking is regulated
by multiple cis-acting elements. As all pathogenic PC1 mutations tested here are
defective in ciliary trafficking, ciliary trafficking might serve as a functional
read-out for ADPKD.
PMID- 26430214
TI - NRIP is newly identified as a Z-disc protein, activating calmodulin signaling for
skeletal muscle contraction and regeneration.
AB - Nuclear receptor interaction protein (NRIP, also known as DCAF6 and IQWD1) is a
Ca(2+)-dependent calmodulin-binding protein. In this study, we newly identify
NRIP as a Z-disc protein in skeletal muscle. NRIP-knockout mice were generated
and found to have reduced muscle strength, susceptibility to fatigue and impaired
adaptive exercise performance. The mechanisms of NRIP-regulated muscle
contraction depend on NRIP being downstream of Ca(2+) signaling, where it
stimulates activation of both 'calcineurin-nuclear factor of activated T-cells,
cytoplasmic 1' (CaN-NFATc1; also known as NFATC1) and calmodulin-dependent
protein kinase II (CaMKII) through interaction with calmodulin (CaM), resulting
in the induction of mitochondrial activity and the expression of genes encoding
the slow class of myosin, and in the regulation of Ca(2+) homeostasis through the
internal Ca(2+) stores of the sarcoplasmic reticulum. Moreover, NRIP-knockout
mice have a delayed regenerative capacity. The amount of NRIP can be enhanced
after muscle injury and is responsible for muscle regeneration, which is
associated with the increased expression of myogenin, desmin and embryonic myosin
heavy chain during myogenesis, as well as for myotube formation. In conclusion,
NRIP is a novel Z-disc protein that is important for skeletal muscle strength and
regenerative capacity.
PMID- 26430215
TI - Vertebrate Reproduction.
AB - Vertebrate reproduction requires a myriad of precisely orchestrated events-in
particular, the maternal production of oocytes, the paternal production of sperm,
successful fertilization, and initiation of early embryonic cell divisions. These
processes are governed by a host of signaling pathways. Protein kinase and
phosphatase signaling pathways involving Mos, CDK1, RSK, and PP2A regulate
meiosis during maturation of the oocyte. Steroid signals-specifically
testosterone-regulate spermatogenesis, as does signaling by G-protein-coupled
hormone receptors. Finally, calcium signaling is essential for both sperm
motility and fertilization. Altogether, this signaling symphony ensures the
production of viable offspring, offering a chance of genetic immortality.
PMID- 26430216
TI - Transcription-Factor-Dependent Control of Adult Hippocampal Neurogenesis.
AB - Adult-generated dentate granule neurons have emerged as major contributors to
hippocampal plasticity. New neurons are generated from neural stem cells through
a complex sequence of proliferation, differentiation, and maturation steps.
Development of the new neuron is dependent on the precise temporal activity of
transcription factors, which coordinate the expression of stage-specific genetic
programs. Here, we review current knowledge in transcription factor-mediated
regulation of mammalian neural stem cells and neurogenesis and will discuss
potential mechanisms of how transcription factor networks, on one hand, allow for
precise execution of the developmental sequence and, on the other hand, allow for
adaptation of the rate and timing of adult neurogenesis in response to complex
stimuli. Understanding transcription factor-mediated control of neuronal
development will provide new insights into the mechanisms underlying neurogenesis
dependent plasticity in health and disease.
PMID- 26430217
TI - Long-Range Chromatin Interactions.
AB - To accommodate genomes in the limited space of the cell nucleus and ensure the
correct execution of gene expression programs, genomes are packaged in complex
fashion in the three-dimensional cell nucleus. As a consequence of the extensive
higher-order organization of chromosomes, distantly located genomic regions on
the same or distinct chromosomes undergo long-range interactions. This article
discusses the nature of long interactions, mechanisms of their formation, and
their emerging functional roles in gene regulation and genome maintenance.
PMID- 26430226
TI - Isolated aortitis: a rare cause of febrile illness.
AB - Febrile illness often presents a challenge for the clinician. The main causes of
febrile illness are infections, solid or haematological malignancies and
connective tissue disorders, including vasculitis. A 49-year-old woman sought
medical attention because of intermittent fever that lasted 2 weeks. She
presented no further symptoms or physical signs to suggest the aetiology. The
epidemiological context was irrelevant. Analyses revealed anaemia of chronic
disease and significant elevations of inflammatory parameters. A comprehensive
study was performed, which revealed presence of an aortitis. Investigation of
infectious and immunological causes was negative. We arrived at the definitive
diagnosis of isolated aortitis. She was treated with corticosteroid and
methotrexate, with resolution of symptoms and clinical abnormalities.
PMID- 26430225
TI - A Physiological and Behavioral Mechanism for Leaf Herbivore-Induced Systemic Root
Resistance.
AB - Indirect plant-mediated interactions between herbivores are important drivers of
community composition in terrestrial ecosystems. Among the most striking examples
are the strong indirect interactions between spatially separated leaf- and root
feeding insects sharing a host plant. Although leaf feeders generally reduce the
performance of root herbivores, little is known about the underlying systemic
changes in root physiology and the associated behavioral responses of the root
feeders. We investigated the consequences of maize (Zea mays) leaf infestation by
Spodoptera littoralis caterpillars for the root-feeding larvae of the beetle
Diabrotica virgifera virgifera, a major pest of maize. D. virgifera strongly
avoided leaf-infested plants by recognizing systemic changes in soluble root
components. The avoidance response occurred within 12 h and was induced by real
and mimicked herbivory, but not wounding alone. Roots of leaf-infested plants
showed altered patterns in soluble free and soluble conjugated phenolic acids.
Biochemical inhibition and genetic manipulation of phenolic acid biosynthesis led
to a complete disappearance of the avoidance response of D. virgifera.
Furthermore, bioactivity-guided fractionation revealed a direct link between the
avoidance response of D. virgifera and changes in soluble conjugated phenolic
acids in the roots of leaf-attacked plants. Our study provides a physiological
mechanism for a behavioral pattern that explains the negative effect of leaf
attack on a root-feeding insect. Furthermore, it opens up the possibility to
control D. virgifera in the field by genetically mimicking leaf herbivore-induced
changes in root phenylpropanoid patterns.
PMID- 26430218
TI - Perisynaptic Schwann Cells at the Neuromuscular Synapse: Adaptable, Multitasking
Glial Cells.
AB - The neuromuscular junction (NMJ) is engineered to be a highly reliable synapse to
carry the control of the motor commands of the nervous system over the muscles.
Its development, organization, and synaptic properties are highly structured and
regulated to support such reliability and efficacy. Yet, the NMJ is also highly
plastic, able to react to injury and adapt to changes. This balance between
structural stability and synaptic efficacy on one hand and structural plasticity
and repair on another hand is made possible by the intricate regulation of
perisynaptic Schwann cells, glial cells at this synapse. They regulate both the
efficacy and structural plasticity of the NMJ in a dynamic, bidirectional manner
owing to their ability to decode synaptic transmission and by their interactions
via trophic-related factors.
PMID- 26430227
TI - Ruptured intercostal artery pseudoaneurysm: a rare cause of acute back pain.
AB - A 63-year-old man with no relevant medical history presented with acute non
traumatic back pain and was found to have a T8 intercostal artery pseudoaneurysm
associated with haemomediastinum on CT of the chest. He was taken to angiography
with interventional radiology and the aneurysm was coiled without complication.
PMID- 26430228
TI - Amitraz: a mimicker of organophosphate poisoning.
AB - Amitraz is used as an ectoparasiticide for dogs and cattle. Human poisoning due
to amitraz may be misdiagnosed as organophosphate/carbamate (OPC) toxicity, since
amitraz poisoning shares several clinical features (miosis, bradycardia and
hypotension) encountered with OPC poisoning. A 19-year-old man with an alleged
history of suicidal ingestion of a pesticide presented with drowsiness and was
found to have constricted pupils, hypotension and bradycardia. He was diagnosed
as a case of OPC poisoning and was treated with atropine and pralidoxime prior to
presentation to our centre. Absence of a hypersecretory state, and the presence
of hyperglycaemia and hypothermia along with a normal serum cholinesterase level
suggested an alternate possibility. Retrieval of the poison container confirmed
the diagnosis of amitraz poisoning. The patient made a rapid recovery with
supportive management. Clinician awareness is key to successful management of
this poisoning, which carries a good prognosis.
PMID- 26430229
TI - Laparoscopic treatment of a large uterine cystic adenomyosis in a young patient.
AB - We describe a rare case of a young woman with a large cystic adenomyotic lesion
that was treated laparoscopically. The patient presented with severe
dysmenorrhoea refractory to common analgaesics. She was initially diagnosed with
right-sided ovarian endometrioma. MRI revealed a cystic lesion of 4 cm attached
to the right uterine wall. Under laparoscopic vision, the uterine lesion was
identified on the right portion of the uterine fundus close to the round
ligament. Monopolar diathermy was used to dissect the lesion. When the incision
reached the cystic cavity, dark-brown content flowed from the cyst. After
resection was complete, the surgical wound was closed with two-layer interrupted
sutures. The patient made a good recovery and was discharged the following day.
Since patients with cystic adenomyosis are young, a minimally invasive procedure
such as laparoscopic excision is considered optimal. The exact topography of the
lesion is crucial in determining the site of the incision.
PMID- 26430230
TI - Imaging of leiomyomas arising from Mullerian remnants in a case of Mayer
Rokitansky-Kuster-Hauser syndrome.
AB - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare congenital abnormality
characterised by varying degrees of aplasia or hypoplasia of the uterus and
vagina. Very rarely, leiomyomas or adenomyosis can develop in the Mullerian
remnant tissue or rudimentary uterus. We present a case of a 43-year-old woman
with MRKH syndrome, who presented with primary amenorrhoea and lower abdominal
pain. On examination, a large pelvic mass was palpated and a provisional
diagnosis of ovarian tumour was made. MRI showed multiple large leiomyomas
arising from the Mullerian remnant tissue, and chronic torsion of the right
ovary.
PMID- 26430231
TI - Peutz-Jeghers syndrome: early clinical expression of a new STK11 gene variant.
AB - Genetic heterogeneity has been recognised in Peutz-Jeghers syndrome (PJS) (over
230 STK11 gene mutations reported). We report a rare PJS phenotype with early
extensive gastrointestinal (GI) presentation and a new genetic variant. The case
presented as haematochezia and mucocutaneous pigmentation (the patient was 3
years of age). Endoscopy showed several polyps throughout the stomach/colon (PJ
type hamartomas); the larger polyps were resected. Small bowel imaging detected
multiple jejunum/ileum small polyps. During 8 years of follow-up of this
asymptomatic patient, an increasing number of diffusely distributed polyps was
observed and polypectomies were performed. Subsequently, the patient failed
consultations; when the patient was 13 years of age, emergency surgery was
required due to small bowel intussusception (ileal polyp). A STK11 gene study
identified two missense variants in heterozygous (yet unknown significance but
probably pathogenic): c.854T>A (exon 6) and c.446C>T* (exon 2) (*not previously
reported). We report two STK11 gene variants (one not previously described) of
yet undetermined causality in a paediatric patient presenting with extensive GI
involvement at a very early age, with no family medical history. Structural and
functional repercussion of the newly described variants should be further
investigated.
PMID- 26430232
TI - Hyperreactio luteinalis encountered during caesarean delivery of an uncomplicated
spontaneous singleton pregnancy.
AB - We report a rare case of hyperreactio luteinalis presenting as an incidental
finding during caesarean section in an uncomplicated spontaneous singleton
pregnancy. Caesarean section was performed due to failure to progress in labour,
and delivered a healthy male neonate. The mother's analytical tests revealed a
hyperandrogenic state without any other relevant alterations. Ovarian volume and
testosterone serum concentration normalised in 2 months. The expectant management
of this case permitted conservation of both ovaries in a young woman without
adding morbidity.
PMID- 26430233
TI - Juvenile fibromyalgia in an adolescent patient with sickle cell disease
presenting with chronic pain.
AB - Juvenile fibromyalgia in children with sickle cell disease has not been reported
in the literature. We report an adolescent patient with sickle cell whose pain
symptoms progressed from having recurrent acute sickle cell pain crisis episodes
to a chronic pain syndrome over several years. He was eventually diagnosed with
juvenile fibromyalgia based on the clinical history and myofascial tender points
and his pain symptoms responded better to multidisciplinary strategies for
chronic fibromyalgia pain. Chronic pain in sickle cell disease is an area of poor
research, and in addition there is inconsistency in the definition of chronic
pain in sickle cell disease. Central sensitisation to pain is shown to occur
after recurrent painful stimuli in a genetically vulnerable individual. In a
chronic pain condition such as fibromyalgia central sensitisation is thought to
play a key role. Fibromyalgia should be considered as one of the main
differential diagnosis in any sickle cell patient with chronic pain.
PMID- 26430234
TI - Rock climbing-related subclavian vein thrombosis.
AB - Paget-Schroetter syndrome, also known as upper extremity deep venous thrombosis
(UEDVT), is a rare condition, characterised by a (sub-) total occlusion of the
axillary-subclavian venous system due to thrombosis. UEDVT is the most common
vascular condition among athletes so far; although the general incidence is low,
this problem will become more frequent as a result of increased participation in
climbing sports. The purpose of this report is to illustrate two cases in rock
climbers where UEDVT developed during rock climbing or bouldering. Fortunately,
both patients were diagnosed relatively early after the symptoms began, despite
the ambiguity of UEDVT symptoms. This relatively unfamiliar condition may become
more highly recognised as a potentially serious differential diagnosis of
unspecific pain of the shoulder. Rock climbers are disposed to develop UEDVT due
to frequent stress on the upper extremities during training or competition.
PMID- 26430235
TI - Budesonide-related adrenal insufficiency.
AB - Iatrogenic adrenal insufficiency is a potential harmful side effect of treatment
with corticosteroids. It manifests itself when an insufficient cortisol response
to biological stress leads to an Addisonian crisis: a life-threatening situation.
We describe a case of a patient who developed an Addisonian crisis after
inappropriate discontinuation of budesonide (a topical steroid used in Crohn's
disease) treatment. Iatrogenic adrenal insufficiency due to budesonide use has
been rarely reported. Prescribers should be aware of the resulting risk for an
Addisonian crisis.
PMID- 26430236
TI - Coevolution of parasite virulence and host mating strategies.
AB - Parasites are thought to play an important role in sexual selection and the
evolution of mating strategies, which in turn are likely to be critical to the
transmission and therefore the evolution of parasites. Despite this clear
interdependence we have little understanding of parasite-mediated sexual
selection in the context of reciprocal parasite evolution. Here we develop a
general coevolutionary model between host mate preference and the virulence of a
sexually transmitted parasite. We show when the characteristics of both the host
and parasite lead to coevolutionarily stable strategies or runaway selection, and
when coevolutionary cycling between high and low levels of host mate choosiness
and virulence is possible. A prominent argument against parasites being involved
in sexual selection is that they should evolve to become less virulent when
transmission depends on host mating success. The present study, however,
demonstrates that coevolution can maintain stable host mate choosiness and
parasite virulence or indeed coevolutionary cycling of both traits. We predict
that choosiness should vary inversely with parasite virulence and that both
relatively long and short life spans select against choosy behavior in the host.
The model also reveals that hosts can evolve different behavioral responses from
the same initial conditions, which highlights difficulties in using comparative
analysis to detect parasite-mediated sexual selection. Taken as a whole, our
results emphasize the importance of viewing parasite-mediated sexual selection in
the context of coevolution.
PMID- 26430237
TI - E1 of alpha-ketoglutarate dehydrogenase defends Mycobacterium tuberculosis
against glutamate anaplerosis and nitroxidative stress.
AB - Enzymes of central carbon metabolism (CCM) in Mycobacterium tuberculosis (Mtb)
make an important contribution to the pathogen's virulence. Evidence is emerging
that some of these enzymes are not simply playing the metabolic roles for which
they are annotated, but can protect the pathogen via additional functions. Here,
we found that deficiency of 2-hydroxy-3-oxoadipate synthase (HOAS), the E1
component of the alpha-ketoglutarate (alpha-KG) dehydrogenase complex (KDHC), did
not lead to general metabolic perturbation or growth impairment of Mtb, but only
to the specific inability to cope with glutamate anaplerosis and nitroxidative
stress. In the former role, HOAS acts to prevent accumulation of aldehydes,
including growth-inhibitory succinate semialdehyde (SSA). In the latter role,
HOAS can participate in an alternative four-component peroxidase system,
HOAS/dihydrolipoyl acetyl transferase (DlaT)/alkylhydroperoxide reductase
colorless subunit gene (ahpC)-neighboring subunit (AhpD)/AhpC, using alpha-KG as
a previously undescribed source of electrons for reductase action. Thus, instead
of a canonical role in CCM, the E1 component of Mtb's KDHC serves key roles in
situational defense that contribute to its requirement for virulence in the host.
We also show that pyruvate decarboxylase (AceE), the E1 component of pyruvate
dehydrogenase (PDHC), can participate in AceE/DlaT/AhpD/AhpC, using pyruvate as a
source of electrons for reductase action. Identification of these systems leads
us to suggest that Mtb can recruit components of its CCM for reactive nitrogen
defense using central carbon metabolites.
PMID- 26430239
TI - Correction for Jimenez-Diaz et al., (+)-SJ733, a clinical candidate for malaria
that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium.
PMID- 26430238
TI - Evolutionary paths of least resistance.
PMID- 26430241
TI - Correction for Colaianni et al., The myokine irisin increases cortical bone mass.
PMID- 26430240
TI - Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by
the central kinetochore Mis12/MIND complex.
AB - Multiple protein subcomplexes of the kinetochore cooperate as a cohesive
molecular unit that forms load-bearing microtubule attachments that drive mitotic
chromosome movements. There is intriguing evidence suggesting that central
kinetochore components influence kinetochore-microtubule attachment, but the
mechanism remains unclear. Here, we find that the conserved Mis12/MIND (Mtw1,
Nsl1, Nnf1, Dsn1) and Ndc80 (Ndc80, Nuf2, Spc24, Spc25) complexes are connected
by an extensive network of contacts, each essential for viability in cells, and
collectively able to withstand substantial tensile load. Using a single-molecule
approach, we demonstrate that an individual MIND complex enhances the microtubule
binding affinity of a single Ndc80 complex by fourfold. MIND itself does not bind
microtubules. Instead, MIND binds Ndc80 complex far from the microtubule-binding
domain and confers increased microtubule interaction of the complex. In addition,
MIND activation is redundant with the effects of a mutation in Ndc80 that might
alter its ability to adopt a folded conformation. Together, our results suggest a
previously unidentified mechanism for regulating microtubule binding of an outer
kinetochore component by a central kinetochore complex.
PMID- 26430243
TI - Illuminating the dark matter in metabolomics.
PMID- 26430242
TI - Endothelial Bmx tyrosine kinase activity is essential for myocardial hypertrophy
and remodeling.
AB - Cardiac hypertrophy accompanies many forms of heart disease, including ischemic
disease, hypertension, heart failure, and valvular disease, and it is a strong
predictor of increased cardiovascular morbidity and mortality. Deletion of bone
marrow kinase in chromosome X (Bmx), an arterial nonreceptor tyrosine kinase, has
been shown to inhibit cardiac hypertrophy in mice. This finding raised the
possibility of therapeutic use of Bmx tyrosine kinase inhibitors, which we have
addressed here by analyzing cardiac hypertrophy in gene-targeted mice deficient
in Bmx tyrosine kinase activity. We found that angiotensin II (Ang II)-induced
cardiac hypertrophy is significantly reduced in mice deficient in Bmx and in mice
with inactivated Bmx tyrosine kinase compared with WT mice. Genome-wide
transcriptomic profiling showed that Bmx inactivation suppresses myocardial
expression of genes related to Ang II-induced inflammatory and extracellular
matrix responses whereas expression of RNAs encoding mitochondrial proteins after
Ang II administration was maintained in Bmx-inactivated hearts. Very little or no
Bmx mRNA was expressed in human cardiomyocytes whereas human cardiac endothelial
cells expressed abundant amounts. Ang II stimulation of endothelial cells
increased Bmx phosphorylation, and Bmx gene silencing inhibited downstream STAT3
signaling, which has been implicated in cardiac hypertrophy. Furthermore,
activation of the mechanistic target of rapamycin complex 1 pathway by Ang II
treatment was decreased in the Bmx-deficient hearts. Our results demonstrate that
inhibition of the cross-talk between endothelial cells and cardiomyocytes by Bmx
inactivation suppresses Ang II-induced signals for cardiac hypertrophy. These
results suggest that the endothelial Bmx tyrosine kinase could provide a target
to attenuate the development of cardiac hypertrophy.
PMID- 26430244
TI - Reply to Sun et al.: Confirming the evidence for Late Oligocene-Early Miocene
birth of the Taklimakan Desert.
PMID- 26430245
TI - Refuting the evidence for an earlier birth of the Taklimakan Desert.
PMID- 26430247
TI - The UK Risk-Sharing Scheme for interferon-beta and glatiramer acetate in multiple
sclerosis. Outcome of the year-6 analysis.
PMID- 26430246
TI - FOXL2 down-regulates vitellogenin expression at mature stage in Eriocheir
sinensis.
AB - Ovarian development in crustaceans is characterized by rapid production of egg
yolk protein in a process called vitellogenesis. In the present study, we
investigated the involvement of a DEAD (Asp-Glu-Ala-Asp) box RNA helicase 20
(DDX20), forkhead transcription factor (FOXL)2 and fushi tarazu factor (FTZ-F)1
in the regulation of vitellogenesis. Based on ESTs from the testis and accessory
gland of Eriocheir sinensis, we cloned the full-length cDNAs of foxl2 and
fushitarazu factor 1 (ftz-f1), which include the conserved structural features of
the forkhead family and nuclear receptor 5A (NR5A) family respectively. The
expression of foxl2 mRNA surged at the mature stage of the ovary, when vtg mRNA
swooped, suggesting that foxl2 negatively affects the vitellogenin (VTG)
synthesis at this developmental stage. Etoposide (inducing germ cell apoptosis)
treatment up-regulated FOXL2 and DDX20 at both the mRNA and the protein levels,
primarily in the follicular cells as shown by immunofluorescence analysis.
Furthermore, foxl2, ddx20 and ftz-f1 mRNA levels increased significantly with
right-eyestalk ablation. Interactions between FOXL2 and DDX20 or FTZ-F1 were
confirmed by co-immunoprecipitation and the forkhead domain of FOXL2 was
identified as the specific structure interacting with FTZ-F1. In conclusion,
FOXL2 down-regulates VTG expression by binding with DDX20 in regulation of
follicular cell apoptosis and with FTZ-F1 to repress the synthesis of VTG at the
mature stage. This report is the first to describe the molecular mechanism of VTG
synthesis in E. sinensis and may shed new light on the regulation of cytochrome
P450 enzyme by FOXL2 and FTZ-F1 in vitellogenesis.
PMID- 26430248
TI - A wolf in sheep's clothing.
PMID- 26430249
TI - Isolation of Chloroplasts from Plant Protoplasts.
AB - Chloroplasts can be isolated from higher plants directly following
homogenization; however, the resulting yield, purity, and intactness are often
low, necessitating a large amount of starting material. This protocol is
optimized to produce a high yield of pure chloroplasts from isolated Arabidopsis
protoplasts. The two-part method is a simple, scaled-down, and low-cost procedure
that readily provides healthy mesophyll protoplasts, which are then ruptured to
release intact chloroplasts. Chloroplasts isolated using this method are
competent for use in biochemical, cellular, and molecular analyses.
PMID- 26430250
TI - Induction of Liver Tumors in Mice with N-Ethyl-N-Nitrosourea or N
Nitrosodiethylamine.
AB - Since the groundbreaking studies in the middle part of the last century showing
liver cancer in rodents exposed to aromatic amines, the liver has been widely
used as a model target organ of chemical carcinogenesis. This protocol describes
a method for inducing liver tumors by injecting mice with the widely used
alkylating agents N-ethyl-N-nitrosourea (ENU) and N-nitrosodiethylamine (DEN).
ENU does not require metabolic activation and readily induces tumors in a number
of tissues, including the lungs, stomach, and ovaries, as well as inducing
lymphomas. Mice injected with DEN can also develop other tumors, including those
of the gastrointestinal tract, skin, lungs, and lymphocytes, but because DEN is
metabolized in the liver, it is most effective at inducing liver tumors.
PMID- 26430251
TI - Induction and Analysis of Synchronous Meiotic Yeast Cultures.
AB - Meiosis in Saccharomyces cerevisiae can be induced by deprivation of nutrients.
Here, we present a protocol for inducing synchronous meiosis in SK1, the most
efficient and synchronous yeast strain for meiosis, by exposing SK1 cells to
liquid medium that contains potassium acetate as a nonfermentable carbon source
and lacks nitrogen. These synchronous meiotic yeast cultures can be subjected to
a range of molecular and cytological analyses, making them useful for
investigating the genetic and molecular determinants of meiosis.
PMID- 26430252
TI - Analysis of Meiotic Recombination and Homolog Interaction during Yeast Meiosis.
AB - During meiosis, one round of genome duplication is followed by two rounds of
chromosome segregation, resulting in the halving of the genetic complement and
the formation of haploid reproductive cells. In most organisms, intimate
juxtaposition of homologous chromosomes and homologous recombination during
meiotic prophase are required for meiotic success. Here we present a general
protocol for visualizing chromosomal proteins and homolog interaction on surface
spread nuclei and a widely used protocol for analyzing meiotic recombination
based on an engineered hotspot referred to as HIS4::LEU2.
PMID- 26430253
TI - Visualizing Lysosomal Membrane Permeabilization by Fluorescent Dextran Release.
AB - Lysosomal membrane permeabilization (LMP) is an effective programmed cell death
pathway triggered in response to a variety of cytotoxic stimuli and cellular
conditions. In the method presented here, LMP is monitored by first taking
advantage of the steady endocytic capacity of cells to load fluorescent dextran
into lysosomes, and then simply observing the translocation of lysosomally
localized dextran into the cytosol after an LMP-inducing insult. Fluorescent
dextran in healthy cells appears in punctate structures representing intact
lysosomes, whereas after LMP, a diffuse staining pattern throughout the cytoplasm
is observed. Using this method, LMP can be followed in real time using time-lapse
imaging. The size of pores formed in the membrane during LMP by size exclusion
can also be determined using dextrans of different sizes and colors.
PMID- 26430254
TI - A Method to Monitor Lysosomal Membrane Permeabilization by Immunocytochemistry.
AB - Programmed cell death involving lysosomal membrane permeabilization (LMP) is a
common phenomenon--more the rule than the exception under various cytotoxic
stimuli and stressful cellular conditions. The protocol presented here is based
on immunocytochemical staining of cathepsin B or L to visualize translocation
from the lysosomal lumen to the cytosol. In healthy cells, cathepsins appear in
localized punctate structures representing intact lysosomes, whereas LMP results
in a diffuse staining pattern throughout the cytoplasm. LMP can be triggered
upstream, downstream, or independently of the classical apoptotic death pathway
involving mitochondrial outer membrane permeabilization (MOMP). Co-staining with
antibodies recognizing the active form of Bax allows investigation of the order
of events between LMP and MOMP in death signaling.
PMID- 26430255
TI - Purification and Injection of Retroviral Vectors.
AB - Retroviral vectors are powerful tools for genetic manipulation. This protocol
discusses the production, purification, and use of replication-deficient
retroviral vectors based on Moloney murine leukemia virus and lentivirus. It also
describes the injection of a retroviral vector into the dentate gyrus of young
adult mice to fluorescently label live murine brain tissue.
PMID- 26430256
TI - Imaging Newborn Granule Cells in Fixed Sections.
AB - This protocol describes the harvesting of brain tissue from mice that have had
the retroviral vector CAG-GFP injected into the dentate gyrus. Brain tissue from
these mice is dissected, the tissue is fixed, and the sections are prepared. The
fixed sections are imaged using fluorescent confocal microscopy, and newborn
granule cells containing GFP are visualized and are characterized.
PMID- 26430257
TI - Analysis of Spine Motility of Newborn Granule Cells in Acute Brain Slices.
AB - In this protocol, acute brain slices are prepared from mice in which newborn
granule cells have been labeled using retroviral vector technology. Using a live
cell imaging stage and confocal microscopy coupled to imaging software, dendritic
spines are analyzed.
PMID- 26430258
TI - Generation of Thy1 Constructs for Pronuclear Injection.
AB - With easy access to core facilities or commercial providers of pronuclear
injections, generating simple Thy1-XFP transgenic mice (where XFP stands for any
fluorescent protein) is now a possibility even for small laboratories. The
generation of new Thy1 transgenic lines generally consists of five steps: (1)
engineering and characterization of the desired fluorescent reporter protein, (2)
cloning of the reporter protein into the Thy1 vector, (3) linearization and
purification of the new Thy1 construct, (4) pronuclear injection to generate
founders, and (5) screening of founder progeny to establish transgenic lines.
Here, we provide a protocol for Steps 2 and 3. The sequence for a desired
fluorescent reporter protein is cloned into the XhoI restriction site of the Thy1
vector. This usually involves blunt-end cloning because the traditional Thy1
vector does not carry an intact multiple cloning site. Following successful
cloning, the DNA is prepared for pronuclear injection by linearizing it using
EcoRI and PvuI restriction enzymes. The purified linearized DNA must then be sent
to a facility specializing in pronuclear injection to generate transgenic founder
mice.
PMID- 26430260
TI - Preparation and Use of Retroviral Vectors for Labeling, Imaging, and Genetically
Manipulating Cells.
AB - Retroviral vectors are a powerful technology for achieving long-term genetic
manipulation. This introduction provides some background on replication-deficient
retroviral vectors based on Moloney murine leukemia virus and lentivirus.
Details, examples, and associated protocols are provided for using these vectors
to fluorescently label, genetically alter, and image both live and fixed murine
brain tissue.
PMID- 26430261
TI - Generation and Screening of Transgenic Mice with Neuronal Labeling Controlled by
Thy1 Regulatory Elements.
AB - Major progress has been made using in vivo imaging in mice to study mammalian
nervous system development, plasticity, and disease. This progress has depended
in part on the wide availability of two-photon microscopy, which is capable of
penetrating deep into scattering tissue. Equally important, however, is the
generation of suitable transgenic mouse models, which provide a "Golgi staining"
like labeling of neurons that is sparse and bright enough for in vivo imaging.
Particularly prominent among such transgenic mice are the so-called Thy1-XFP mice
(in which XFP stands for any fluorescent protein) that are used in numerous
studies, especially to visualize spine plasticity in the cortex and remodeling in
peripheral synapses. New generations of Thy1-XFP mice are now being generated at
a high rate, and these have allowed previously difficult experiments to become
feasible. Moreover, with easy access to core facilities or commercial providers
of pronuclear injections, generating simple Thy1 transgenic mice is now a
possibility even for small laboratories. In this introduction, we discuss the
Thy1 regulatory elements used to generate transgenic lines with neuronal
labeling. We provide a brief overview of currently available Thy1 transgenic
mice, including lines labeling neuronal organelles or reporting neuronal
function.
PMID- 26430259
TI - Animal Models of Chemical Carcinogenesis: Driving Breakthroughs in Cancer
Research for 100 Years.
AB - The identification of carcinogens in the workplace, diet, and environment through
chemical carcinogenesis studies in animals has directly contributed to a
reduction of cancer burden in the human population. Reduced exposure to these
carcinogens through lifestyle changes, government regulation, or change in
industry practices has reduced cancer incidence in exposed populations. In
addition to providing the first experimental evidence for cancer's relationship
to chemical and radiation exposure, animal models of environmentally induced
cancer have and will continue to provide important insight into the causes,
mechanisms, and conceptual frameworks of cancer. More recently, combining
chemical carcinogens with genetically engineered mouse models has emerged as an
invaluable approach to study the complex interaction between genotype and
environment that contributes to cancer development. In the future, animal models
of environmentally induced cancer are likely to provide insight into areas such
as the epigenetic basis of cancer, genetic modifiers of cancer susceptibility,
the systems biology of cancer, inflammation and cancer, and cancer prevention.
PMID- 26430262
TI - MEET THE PRESIDENT.
PMID- 26430263
TI - A Year in Third Person.
PMID- 26430264
TI - AJPE Welcomes Fjortoft and Schlesselman as Associate Editors.
PMID- 26430265
TI - An Interprofessional Education Panel on Development, Implementation, and
Assessment Strategies.
AB - This report provides a primer for implementing interprofessional education (IPE)
within pharmacy and health sciences curricula. In 2013, a panel of administrators
and faculty members, whose institutions offered IPE, funded by the Josiah Macy
Jr. Foundation, shared best collaborative practice models at the American
Association of Colleges of Pharmacy (AACP) Annual Meeting. These presenters
subsequently collaborated to write a primer as guidance for other institutions
interested in successfully implementing and continuously enhancing the quality of
IPE programs. In this article, these IPE faculty members provide a rationale for
creating IPE reforms, discuss successful strategies for innovative IPE programs,
and share lessons learned for implementing effective assessment tools. A
structure and process for determining outcomes of IPE models are presented and
strategies for exploring shared education opportunities across health professions
and for integrating top-down and bottom-up methods for IPE programs are given.
PMID- 26430266
TI - Personal Digital Branding as a Professional Asset in the Digital Age.
AB - In recent years, society's rapid adoption of social media has made the boundary
between professional and private life nearly indistinguishable. The literature
provides guidance on how to demonstrate professionalism via social media
platforms. Social media policies within health professions education tend to be
legalistic in nature, serving primarily to highlight behaviors students should
avoid. One missing element in social media literature is the concept of online
invisibility. In this paper, we define personal digital branding, discuss the
professional implications of choosing to abstain from social media use, and urge
educators to recognize that the personal digital branding may be an emerging
asset for young professionals in the twenty-first century.
PMID- 26430267
TI - Outcomes of a Multi-faceted Educational Intervention to Increase Student
Scholarship.
AB - Objective. To increase the percentage of state, national, or international
student presentations and publications. Design. A multi-faceted intervention to
increase student scholarly output was developed that included: (1) a 120-minute
lecture on publication of quality improvement or independent study research
findings; (2) abstract workshops; (3) poster workshops; and (4) a reminder at an
advanced pharmacy practice experience (APPE) meeting encouraging students to
publish or present posters. The intervention effect was measured as the percent
of students who presented at meetings and the number of student projects
published. Assessment. A significant increase occurred in the percent of students
who presented posters or published manuscripts after the intervention (64% vs
81%). Total student productivity increased from 84 to 147 posters, publications,
and presentations. The number of projects presented or published increased from
50 to 77 in one year. Conclusion. This high-impact, low-cost intervention
increased scholarly output and may help students stand out in a competitive job
market.
PMID- 26430268
TI - A Learner-led, Discussion-based Elective on Emerging Infectious Disease.
AB - Objective. To implement a learner-led, discussion-based course aimed at exposing
second-year pharmacy learners to the study of emerging infectious diseases from a
global health perspective and to assess the role and importance of pharmacists in
the management of disease outbreaks. Design. Learners examined literature
pertinent to an emerging infectious disease in a 3-credit, discussion-based
course and participated in peer discussion led by a designated learner.
Instructional materials included journal articles, audio-visual presentations,
documentaries, book chapters, movies, newspaper/magazine articles, and other
materials. Learning outcomes were measured based on the ability of learners to
perform critical thinking and analysis, communicate with their peers, and
participate in class discussions. Assessment. The course was offered to 2
consecutive cohorts consisting of 14 and 16 learners, respectively. Overall,
every learner in the first cohort achieved a final grade of A for the course. In
the second cohort, the overall grade distribution consisted of grades of A, B,
and C for the course. Learner evaluations indicated that the active-learning,
discussion-based environment significantly enhanced interest in the topic and
overall performance in the course. Conclusion. The elective course on emerging
infectious diseases provided in-depth exposure to disease topics normally not
encountered in the pharmacy curriculum. Learners found the material and format
valuable, and the course enhanced their appreciation of infectious diseases,
research methodology, critical thinking and analysis, and their roles as
pharmacists.
PMID- 26430269
TI - Evolution of a Natural Products and Nutraceuticals Course in the Pharmacy
Curriculum.
AB - Objective. To develop, implement, and modify a required, second-year pharmacy
course that provides an understanding of the scientific, therapeutic, and
clinical principles, as well as the evidence-based medicine underlying the use of
natural products. Design. A 28-hour, multi-faculty course was developed and
offered in 2008. The course was modified over the years to enhance students'
practice skills in the use of natural products. A course evaluation and survey
were administered to assess the students' opinions. Assessment. Students
performed well in the course and provided favorable evaluations, especially for
the latest offering. Students reported significantly improved skills in providing
advice to patients regarding the use of natural products. Conclusion. The course
increased the students' knowledge and application of information and counseling
skills regarding natural products.
PMID- 26430271
TI - Limited Predictive Utility of Admissions Scores and Objective Structured Clinical
Examinations for APPE Performance.
AB - OBJECTIVE: To examine the relationship between admissions, objective structured
clinical examination (OSCE), and advanced pharmacy practice experience (APPE)
scores. METHODS: Admissions, OSCE, and APPE scores were collected for students
who graduated from the doctor of pharmacy (PharmD) program in spring of 2012 and
spring of 2013 (n=289). Pearson correlation was used to examine relationships
between variables, and independent t test was used to compare mean scores between
groups. RESULTS: All relationships among admissions data (undergraduate grade
point average, composite PCAT scores, and interview scores) and OSCE and APPE
scores were weak, with the strongest association found between the final OSCE and
ambulatory care APPEs. Students with low scores on the final OSCE performed lower
than others on the acute care, ambulatory care, and community APPEs. CONCLUSION:
This study highlights the complexities of assessing student development of
noncognitive professional skills over the course of a curriculum.
PMID- 26430270
TI - Fostering Interdisciplinary Communication between Pharmacy and Nursing Students.
AB - Objective. To evaluate pharmacy and nursing student self-perceptions of
interdisciplinary communication skills, faculty member perceptions of
interdisciplinary communication skills, and changes in those skills after
increasing the interdisciplinary education content. Design. Two cohorts of
pharmacy and nursing (bachelors of science in nursing, BSN) students in
respective, semester-long research courses engaged in active learning on
interdisciplinary communication, with the second cohort receiving additional
content on the topic. At semester completion, students presented a research
project at an interdisciplinary poster session. Assessment. Self-, peer-, and
faculty evaluations (4 items; 5-point Likert-type) assessing self-confidence and
actual interdisciplinary communication skills were completed during the poster
session. Overall, students responded they were "very confident" or "extremely
confident" regarding the skills, with greater confidence reported by the second
cohort. Faculty members agreed that students exhibited effective
interdisciplinary communication skills, with stronger agreement for the second
cohort. Conclusion. Including interdisciplinary education and experiences in a
curriculum increases students' interdisciplinary communication skills. Using
multiple interdisciplinary experiences may result in greater increases in these
skills.
PMID- 26430272
TI - Pharmacy Students' Knowledge and Attitudes Regarding Medical Marijuana.
AB - OBJECTIVE: To determine pharmacy students' knowledge of and attitudes toward
medical marijuana and to determine if pharmacy students need additional education
on the topic. METHODS: Pharmacy students were asked to complete a survey on
medical marijuana that assessed their knowledge of, medical uses of, adverse
effects with, and attitudes toward medical marijuana through 23 Likert-scale
questions. RESULTS: Three hundred eleven students completed the survey. Fifty
eight percent of the students felt that medical marijuana should be legalized in
all states. However, the majority of students did not feel comfortable answering
consumers' questions regarding efficacy, safety, or drug interactions related to
the substance. Accurate responses for diseases or conditions for permitted
medical marijuana use was low, with only cancer (91%) and glaucoma (57%)
identified by more than half the students. CONCLUSION: With an increasing number
of states adopting medical marijuana use, pharmacy schools need to evaluate the
adequacy of medical marijuana education in their curriculum.
PMID- 26430273
TI - Assessment of Communications-related Admissions Criteria in a Three-year Pharmacy
Program.
AB - OBJECTIVE: To determine if there is a correlation between TOEFL and other
admissions criteria that assess communications skills (ie, PCAT variables:
verbal, reading, essay, and composite), interview, and observational scores and
to evaluate TOEFL and these admissions criteria as predictors of academic
performance. METHODS: Statistical analyses included two sample t tests, multiple
regression and Pearson's correlations for parametric variables, and Mann-Whitney
U for nonparametric variables, which were conducted on the retrospective data of
162 students, 57 of whom were foreign-born. RESULTS: The multiple regression
model of the other admissions criteria on TOEFL was significant. There was no
significant correlation between TOEFL scores and academic performance. However,
significant correlations were found between the other admissions criteria and
academic performance. CONCLUSION: Since TOEFL is not a significant predictor of
either communication skills or academic success of foreign-born PharmD students
in the program, it may be eliminated as an admissions criterion.
PMID- 26430274
TI - Collaborative Examination Item Review Process in a Team-Taught, Self-Care
Sequence.
AB - OBJECTIVE: To improve examination item quality by educating and involving course
instructors in evidence-based item review and encouraging use of this process in
future courses. METHODS: A peer-review process was implemented in a 2-course
sequence (intervention) that involved training and review sessions before each
examination and was compared to the previous year's courses (control).
Instructors completed a presurvey and postsurvey on training, experience, self
confidence, and self-rated success in multiple-choice item writing. Statistics
were calculated for all items in the control and intervention sequences and
compared using independent t tests. Items also were classified into levels based
on difficulty and discrimination, and distribution into these levels was compared
between sequences with independent t tests. RESULTS: No significant difference
was found between control and intervention sequence items with regard to mean
difficulty (86.3% and 84.4%) or discrimination (0.23- and 0.25), respectively,
although item classification distribution did appear to change between the
control and intervention sequences' subjective feelings of confidence, and
success in item writing increased between presurvey and postsurvey. Confidence in
ability to peer-review test items and to implement a formal item evaluation
process also increased. CONCLUSION: Item statistics did not change significantly,
but reviewed and edited items distributed more favorably into item statistic
based categories. This method of review positively affected instructors'
perceptions of their item-writing confidence and success and improved self-rated
opinions of their ability to edit items and train others to do so.
PMID- 26430275
TI - Career Placement of Doctor of Pharmacy Graduates at Eight U.S. Midwestern
Schools.
AB - OBJECTIVE: To characterize postgraduation placement plans of 2013 doctor of
pharmacy (PharmD) graduates. METHODS: A cross-sectional survey of PharmD
graduates from 8 midwestern colleges of pharmacy was designed to capture a
comprehensive picture of graduating students' experiences and outcomes of their
job search. RESULTS: At graduation, 81% of 2013 respondents had postgraduate
plans, with approximately 40% accepting jobs and 40% accepting residencies or
fellowships. Eighty-four percent of graduates reported being pleased with offers
received, and 86% received placement in their preferred practice setting.
Students perceived that securing residencies was more difficult than securing
jobs. Students who participated in key activities had a nearly sevenfold increase
in successful residency placement. CONCLUSION: While the demand for pharmacists
decreased in recent years, responses indicated successful placement by the
majority of 2013 graduates at the time of graduation.
PMID- 26430276
TI - Development and Assessment of a Horizontally Integrated Biological Sciences
Course Sequence for Pharmacy Education.
AB - OBJECTIVE: To design and assess a horizontally integrated biological sciences
course sequence and to determine its effectiveness in imparting the foundational
science knowledge necessary to successfully progress through the pharmacy school
curriculum and produce competent pharmacy school graduates. DESIGN: A 2-semester
course sequence integrated principles from several basic science disciplines:
biochemistry, molecular biology, cellular biology, anatomy, physiology, and
pathophysiology. Each is a 5-credit course taught 5 days per week, with 50-minute
class periods. ASSESSMENT: Achievement of outcomes was determined with course
examinations, student lecture, and an annual skills mastery assessment. The North
American Pharmacist Licensure Examination (NAPLEX) results were used as an
indicator of competency to practice pharmacy. CONCLUSION: Students achieved
course objectives and program level outcomes. The biological sciences integrated
course sequence was successful in providing students with foundational basic
science knowledge required to progress through the pharmacy program and to pass
the NAPLEX. The percentage of the school's students who passed the NAPLEX was not
statistically different from the national percentage.
PMID- 26430277
TI - Using the Jigsaw Technique to Teach Clinical Controversy in a Clinical Skills
Course.
AB - OBJECTIVE: To evaluate the effectiveness and student perception of the jigsaw
technique to engage students in a clinical controversy exercise and to assess
student engagement level during each step of the process. DESIGN: Students were
assigned individual readings pertaining to the controversy surrounding the drug
oxybutynin switching from prescription to nonprescription. They met with an
expert group and teaching groups during mandatory laboratory time and worked
together to formulate a recommendation on the appropriateness of nonprescription
conversion for a drug. ASSESSMENT: A quiz taken individually was used to measure
effectiveness. Student perception and level of engagement was assessed using
surveys. CONCLUSION: The jigsaw technique was successful in teaching the concepts
involved in the clinical controversy. Group members rated themselves and fellow
participants' level of engagement as high during both the expert group and
teaching group sessions. Most students reported they learned about the same or
more with the jigsaw technique compared to another cooperative learning technique
used in the curriculum.
PMID- 26430279
TI - What Can We Learn from TED Talks?
PMID- 26430278
TI - Evaluating the Effects of Flexible Learning about Aseptic Compounding on First
year Students in a Pharmacy Skills Laboratory.
AB - OBJECTIVE: To evaluate how flexible learning via online video review affects the
ability and confidence of first-year (P1) pharmacy students to accurately
compound aseptic preparations. DESIGN: Customary instructions and assignments for
aseptic compounding were provided to students, who were given unlimited access to
5 short review videos in addition to customary instruction. Student self
confidence was assessed online, and faculty members evaluated students' aseptic
technique at the conclusion of the semester. ASSESSMENT: No significant
difference on final assessment scores was observed between those who viewed
videos and those who did not. Student self-confidence scores increased
significantly from baseline, but were not significantly higher for those who
viewed videos than for those who did not. CONCLUSION: First-year students
performed well on final aseptic compounding assessments, and those who viewed
videos had a slight advantage. Student self-confidence improved over the semester
regardless of whether or not students accessed review videos.
PMID- 26430280
TI - Response to Letter Regarding TED Talks.
PMID- 26430281
TI - Capitalizing on Foundations in Citizenship Address of the 2014-2015 President
elect to the 2015 AACP House of Delegates.
PMID- 26430282
TI - The Production of Inequality: The Gender Division of Labor Across the Transition
to Parenthood.
AB - Using longitudinal time diary and survey data from a community sample of dual
earner couples across the transition to parenthood, the authors examined change
in divisions of paid and unpaid work and assessed the accuracy of survey data for
time use measurement. Mothers, according to the time diaries, shouldered the
majority of child care and did not decrease their paid work hours. Furthermore,
the gender gap was not present prebirth but emerged postbirth with women doing
more than 2 hours of additional work per day compared to an additional 40 minutes
for men. Moreover, the birth of a child magnified parents' overestimations of
work in the survey data, and had the authors relied only on survey data, gender
work inequalities would not have been apparent. The findings have important
implications for (a) the state of the gender revolution among couples well
positioned to obtained balanced workloads and (b) the utility of survey data to
measure parents' division of labor.
PMID- 26430283
TI - Phosphate Tether-Mediated Ring-Closing Metathesis for the Generation of Medium to
Large, P-Stereogenic Bicyclo[n.3.1]phosphates.
AB - A phosphate tether-mediated ring-closing metathesis study towards the synthesis
of P-stereogenic bicyclo[6.3.1]-, bicyclo[7.3.1]-, and bicyclo[8.3.1]phosphates
is reported. This study demonstrates expanded utility of phosphate tether
mediated desymmetrization of C2-symmetric, 1,3-anti-diol dienes in generating
complex medium to large, P-stereogenic bicyclo[n.3.1]phosphates..
PMID- 26430284
TI - Filipino-American Nurses' Knowledge, Perceptions, Beliefs and Practice of
Genetics and Genomics.
AB - INTRODUCTION: There is limited information on the knowledge, perceptions,
beliefs, and practice, about genetics and genomics among Filipino-American
nurses. The National Coalition of Ethnic Minority Organizations (NCEMNA), in
which the Philippine Nurses Association of America (PNAA) is a member
organization, conducted an online survey to describe the genomic knowledge,
perceptions, beliefs, and practice of minority nurses. This study reports on
responses from Filipino-American survey participants, which is a subset analysis
of the larger NCEMNA survey. OBJECTIVE: The purpose of this study was to explore
the knowledge, perceptions, beliefs, practice and genomic education of Filipino
American nurses. METHOD: An online survey of 112 Filipino-American nurses was
conducted to describe the knowledge, perceptions, beliefs, and practice of
genetics/genomics. Survey responses were analyzed using descriptive statistics.
RESULTS: Most (94%) Filipino-American nurses wanted to learn more about genetics.
Although 41% of the respondents indicated good understanding of genetics of
common diseases, 60% had not attended any related continuing education courses
since RN licensure, and 73% reported unavailability of genetic courses to take.
The majority (83%) of PNAA respondents indicated that they would attend
genetics/genomics awareness training if it was offered by their national
organization during their annual conference, and 86% reported that the national
organization should have a visible role in genetics/genomics initiatives in their
community. CONCLUSION: Filipino-American nurses wanted to learn more about
genetics and were willing to attend genetics/genomics trainings if offered by
PNAA. The study findings can assist PNAA in planning future educational programs
that incorporates genetics and genomics information.
PMID- 26430285
TI - A review of radio channel models for body centric communications.
AB - The human body is an extremely challenging environment for the operation of
wireless communications systems, not least because of the complex antenna-body
electromagnetic interaction effects which can occur. This is further compounded
by the impact of movement and the propagation characteristics of the local
environment which all have an effect upon body centric communications channels.
As the successful design of body area networks (BANs) and other types of body
centric system is inextricably linked to a thorough understanding of these
factors, the aim of this paper is to conduct a survey of the current state of the
art in relation to propagation and channel models primarily for BANs but also
considering other types of body centric communications. We initially discuss some
of the standardization efforts performed by the Institute of Electrical and
Electronics Engineers 802.15.6 task group before focusing on the two most popular
types of technologies currently being considered for BANs, namely narrowband and
Ultrawideband (UWB) communications. For narrowband communications the
applicability of a generic path loss model is contended, before presenting some
of the scenario specific models which have proven successful. The impacts of
human body shadowing and small-scale fading are also presented alongside some of
the most recent research into the Doppler and time dependencies of BANs. For UWB
BAN communications, we again consider the path loss as well as empirical tap
delay line models developed from a number of extensive channel measurement
campaigns conducted by research institutions around the world. Ongoing efforts
within collaborative projects such as Committee on Science and Technology Action
IC1004 are also described. Finally, recent years have also seen significant
developments in other areas of body centric communications such as off-body and
body-to-body communications. We highlight some of the newest relevant research in
these areas as well as discussing some of the advanced topics which are currently
being addressed in the field of body centric communications.
PMID- 26430286
TI - Comparison of two confocal micro-XRF spectrometers with different design aspects.
AB - Two different confocal micro X-ray fluorescence spectrometers have been developed
and installed at Osaka City University and the Vienna University of Technology
Atominstitut. The Osaka City University system is a high resolution spectrometer
operating in air. The Vienna University of Technology Atominstitut spectrometer
has a lower spatial resolution but is optimized for light element detection and
operates under vacuum condition. The performance of both spectrometers was
compared. In order to characterize the spatial resolution, a set of nine
specially prepared single element thin film reference samples (500 nm in
thickness, Al, Ti, Cr, Fe Ni, Cu, Zr, Mo, and Au) was used. Lower limits of
detection were determined using the National Institute of Standards and
Technology standard reference material glass standard 1412. A paint layer sample
(cultural heritage application) and paint on automotive steel samples were
analyzed with both instruments. The depth profile information was acquired by
scanning the sample perpendicular to the surface. (c) 2013 The Authors. X-Ray
Spectrometry published by John Wiley & Sons, Ltd.
PMID- 26430287
TI - Perpetrators of Alcohol-Involved Sexual Assaults: How Do They Differ From Other
Sexual Assault Perpetrators and Nonperpetrators?
AB - Approximately 50% of sexual assaults involve alcohol. Researchers have documented
situational characteristics that distinguish between sexual assaults that do and
do not involve alcohol, but little attention has been paid to differences between
the perpetrators of these two types of assault. In this study, discriminant
function analysis was used to distinguish between college men (N = 356) who
reported perpetrating sexual assault that involved alcohol, sexual assault that
did not involve alcohol, or no sexual assault. Predictors of sexual assault
perpetration that have been documented in past research differentiated
nonperpetrators from both types of perpetrators. Perpetrators of sexual assaults
that involved alcohol were in most ways similar to perpetrators of sexual
assaults that did not, although they did differ on impulsivity, alcohol
consumption in sexual situations, and beliefs about alcohol. These findings
suggest mechanisms through which alcohol is involved in sexual assault that are
relevant to theory and prevention.
PMID- 26430288
TI - Reciprocity as a Foundation of Financial Economics.
AB - This paper argues that the subsistence of the fundamental theorem of contemporary
financial mathematics is the ethical concept 'reciprocity'. The argument is based
on identifying an equivalence between the contemporary, and ostensibly 'value
neutral', Fundamental Theory of Asset Pricing with theories of mathematical
probability that emerged in the seventeenth century in the context of the ethical
assessment of commercial contracts in a framework of Aristotelian ethics. This
observation, the main claim of the paper, is justified on the basis of results
from the Ultimatum Game and is analysed within a framework of Pragmatic
philosophy. The analysis leads to the explanatory hypothesis that markets are
centres of communicative action with reciprocity as a rule of discourse. The
purpose of the paper is to reorientate financial economics to emphasise the
objectives of cooperation and social cohesion and to this end, we offer specific
policy advice.
PMID- 26430289
TI - Early Language and Reading Development of Bilingual Preschoolers From Low-Income
Families.
AB - Learning to read is a complex process and a number of factors affect a child's
success in beginning reading. This complexity increases when a child's home
language differs from that of the school and when the child comes from a home
with limited economic resources. This article discusses factors that have been
shown to contribute to children's success in early reading, namely-phonological
awareness, letter-word identification, oral language, and the home literacy
environment. Preliminary evidence suggests that bilingual children from low
income backgrounds initially perform poorly on phonological awareness and letter
identification tasks, but appear to acquire these abilities quickly in
kindergarten once these abilities are emphasized in early reading instruction. In
addition, the findings show that bilingual preschoolers' receptive language
abilities in English and Spanish positively impact their early letter-word
identification abilities at the end of kindergarten. A positive relationship
between bilingual preschoolers' home literacy environment and early reading
outcomes has not been found to date. Educational implications for serving young,
bilingual children from programs such as Head Start are discussed.
PMID- 26430290
TI - A Real-Time Skin Dose Tracking System for Biplane Neuro-Interventional
Procedures.
AB - A biplane dose-tracking system (Biplane-DTS) that provides a real-time display of
the skin-dose distribution on a 3D-patient graphic during neuro-interventional
fluoroscopic procedures was developed. Biplane-DTS calculates patient skin dose
using geometry and exposure information for the two gantries of the imaging
system acquired from the digital system bus. The dose is calculated for
individual points on the patient graphic surface for each exposure pulse and
cumulative dose for both x-ray tubes is displayed as color maps on a split screen
showing frontal and lateral projections of a 3D-humanoid graphic. Overall peak
skin dose (PSD), FOV-PSD and current dose rates for the two gantries are also
displayed. Biplane-DTS uses calibration files of mR/mAs for the frontal and
lateral tubes measured with and without the table in the beam at the entrance
surface of a 20 cm thick PMMA phantom placed 15 cm tube-side of the isocenter.
For neuro-imaging, conversion factors are applied as a function of entrance field
area to scale the calculated dose to that measured with a Phantom Laboratory head
phantom which contains a human skull to account for differences in backscatter
between PMMA and the human head. The software incorporates inverse-square
correction to each point on the skin and corrects for angulation of the beam
through the table. Dose calculated by Biplane DTS and values measured by a 6-cc
ionization chamber placed on the head phantom at multiple points agree within a
range of -3% to +7% with a standard deviation for all points of less than 3%.
PMID- 26430291
TI - Estimating ROI activity concentration with photon-processing and photon-counting
SPECT imaging systems.
AB - Recently a new class of imaging systems, referred to as photon-processing (PP)
systems, are being developed that uses real-time maximum-likelihood (ML) methods
to estimate multiple attributes per detected photon and store these attributes in
a list format. PP systems could have a number of potential advantages compared to
systems that bin photons based on attributes such as energy, projection angle,
and position, referred to as photon-counting (PC) systems. For example, PP
systems do not suffer from binning-related information loss and provide the
potential to extract information from attributes such as energy deposited by the
detected photon. To quantify the effects of this advantage on task performance,
objective evaluation studies are required. We performed this study in the context
of quantitative 2-dimensional single-photon emission computed tomography (SPECT)
imaging with the end task of estimating the mean activity concentration within a
region of interest (ROI). We first theoretically outline the effect of null space
on estimating the mean activity concentration, and argue that due to this effect,
PP systems could have better estimation performance compared to PC systems with
noise-free data. To evaluate the performance of PP and PC systems with noisy
data, we developed a singular value decomposition (SVD)-based analytic method to
estimate the activity concentration from PP systems. Using simulations, we
studied the accuracy and precision of this technique in estimating the activity
concentration. We used this framework to objectively compare PP and PC systems on
the activity concentration estimation task. We investigated the effects of
varying the size of the ROI and varying the number of bins for the attribute
corresponding to the angular orientation of the detector in a continuously
rotating SPECT system. The results indicate that in several cases, PP systems
offer improved estimation performance compared to PC systems.
PMID- 26430292
TI - Objective evaluation of reconstruction methods for quantitative SPECT imaging in
the absence of ground truth.
AB - Quantitative single-photon emission computed tomography (SPECT) imaging is
emerging as an important tool in clinical studies and biomedical research. There
is thus a need for optimization and evaluation of systems and algorithms that are
being developed for quantitative SPECT imaging. An appropriate objective method
to evaluate these systems is by comparing their performance in the end task that
is required in quantitative SPECT imaging, such as estimating the mean activity
concentration in a volume of interest (VOI) in a patient image. This objective
evaluation can be performed if the true value of the estimated parameter is
known, i.e. we have a gold standard. However, very rarely is this gold standard
known in human studies. Thus, no-gold-standard techniques to optimize and
evaluate systems and algorithms in the absence of gold standard are required. In
this work, we developed a no-gold-standard technique to objectively evaluate
reconstruction methods used in quantitative SPECT when the parameter to be
estimated is the mean activity concentration in a VOI. We studied the performance
of the technique with realistic simulated image data generated from an object
database consisting of five phantom anatomies with all possible combinations of
five sets of organ uptakes, where each anatomy consisted of eight different organ
VOIs. Results indicate that the method provided accurate ranking of the
reconstruction methods. We also demonstrated the application of consistency
checks to test the no-gold-standard output.
PMID- 26430293
TI - Application of Regulatory Focus Theory to Search Advertising.
AB - PURPOSE: The purpose of this paper is to test the utility of regulatory focus
theory principles in a real-world setting; specifically, Internet hosted text
advertisements. Effect of compatibility of the ad text with the regulatory focus
of the consumer was examined. DESIGN/METHODOLOGY/APPROACH: Advertisements were
created using Google AdWords. Data were collected for the number of views and
clicks each ad received. Effect of regulatory fit was measured using logistic
regression. FINDINGS: Logistic regression analyses demonstrated that there was a
strong main effect for keyword, such that users were almost six times as likely
to click on a promotion advertisement as a prevention advertisement, as well as a
main effect for compatibility, such that users were twice as likely to click on
an advertisement with content that was consistent with their keyword. Finally,
there was a strong interaction of these two variables, such that the effect of
consistent advertisements was stronger for promotion searches than for prevention
searches. RESEARCH LIMITATIONS/IMPLICATIONS: The effect of ad compatibility had
medium to large effect sizes, suggesting that individuals' state may have more
influence on advertising response than do individuals' traits (e.g. personality
traits). Measurement of regulatory fit was limited by the constraints of Google
AdWords. PRACTICAL IMPLICATIONS: The results of this study provide a possible
framework for ad creation for Internet advertisers. ORIGINALITY/VALUE: This paper
is the first study to demonstrate the utility of regulatory focus theory in
online advertising.
PMID- 26430294
TI - Uncertain future, non-numeric preferences, and the fertility transition: A case
study of rural Mozambique.
AB - In many high-fertility countries, and especially in sub-Saharan Africa,
substantial proportions of women give non-numeric responses when asked about
desired family size. Demographic transition theory has interpreted responses of
"don't know" or "up to God" as evidence of fatalistic attitudes toward
childbearing. Alternatively, these responses can be understood as meaningful
reactions to uncertainty about the future. Following this latter approach, we use
data from rural Mozambique to test the hypothesis that non-numeric responses are
more common when uncertainty about the future is greater. We expand on previous
research linking child mortality and non-numeric fertility preferences by testing
the predictive power of economic conditions, marital instability, and adult
mortality. Results show that uncertainty related to adult and child mortality and
to economic conditions predicts non-numeric responses, while marital stability is
less strongly related.
PMID- 26430295
TI - Challenges of a healthy lifestyle for socially disadvantaged people of Dutch,
Moroccan and Turkish origin in the Netherlands: a focus group study.
AB - Lifestyle interventions often fail to successfully reach individuals with lower
socio-economic status (SES), possibly because of the individual behavioural
orientation to health behaviour and because limited research has included the
target groups' perspectives in the development of interventions. Certainly, in
order to make lifestyle interventions more applicable, target groups' viewpoints
should to be taken into account. In order to tailor an effective lifestyle
intervention to groups with lower SES of different ethnic origins, 14 focus group
interviews were conducted with Turkish, Moroccan and Dutch male and female
groups. The target groups' responses highlight their viewpoint and their dilemmas
with regard to physical activity behaviour and healthy eating. Exploration of the
target groups' behaviour in terms of their own logic revealed three prominent
themes. Firstly, some individuals find it difficult to maintain healthy eating
habits and regular physical activities, as their concept of a healthy life
comprises competing values and activities. Secondly, social norms and social
practices of others influence health behaviour. Thirdly, respondents' answers
reflect how they deal with the dilemma of competing values and norms. They use
different ways of reasoning to make sense of their own (health) behaviour. Taken
together, the results of this study suggest that considering physical activity
and eating as collective social practices rather than as determinants of health
will provide new opportunities to initiate healthy lifestyles and to make
lifestyle interventions more applicable to target groups' realities.
PMID- 26430296
TI - Shear bond strength of computer-aided design and computer-aided manufacturing
feldspathic and nano resin ceramics blocks cemented with three different
generations of resin cement.
AB - AIM: To evaluate the shear bond strength between the dentin substrate and
computer-aided design and computer-aided manufacturing feldspathic ceramic and
nano resin ceramics blocks cemented with resin cement. MATERIALS AND METHODS:
Sixty cuboidal blocks (5 mm * 5 mm * 5 mm) were fabricated in equal numbers from
feldspathic ceramic CEREC((r)) Blocs PC and nano resin ceramic LavaTM Ultimate,
and randomly divided into six groups (n = 10). Each block was cemented to the
dentin of 60 extracted human premolar using Variolink((r)) II/Syntac Classic
(multi-steps etch-and-rinse adhesive bonding), NX3 Nexus((r)) (two-steps etch-and
rinse adhesive bonding) and RelyXTM U200 self-adhesive cement. All specimens were
thermocycled, and shear bond strength testing was done using the universal
testing machine at a crosshead speed of 1.0 mm/min. Data were analyzed using one
way ANOVA. RESULTS: Combination of CEREC((r)) Blocs PC and Variolink((r)) II
showed the highest mean shear bond strength (8.71 Mpa), while the lowest of 2.06
Mpa were observed in LavaTM Ultimate and RelyXTM U200. There was no significant
difference in the mean shear bond strength between different blocks. CONCLUSION:
Variolink((r)) II cement using multi-steps etch-and-rinse adhesive bonding
provided a higher shear bond strength than the self-adhesive cement RelyX U200.
The shear bond strength was not affected by the type of blocks used.
PMID- 26430297
TI - Effect of bromelain enzyme for dentin deproteinization on bond strength of
adhesive system.
AB - AIMS: To assess the deproteinizing effect of bromelain enzyme and compare it with
5% sodium hypochlorite (NaOCl) on shear bond strength before application of the
adhesive system. MATERIALS AND METHODS: A total of 30 extracted human premolars
were divided into three groups, each one consisted of 10 teeth. The occlusal
surface was wet ground to expose superficial dentin. In Group 1, teeth were
etched; in Group 2, teeth were etched and deproteinized with bromelain enzyme; in
Group 3, teeth were etched and deproteinized with 5% NaOCl. Upon completion of
the adhesive procedures, resin composite was inserted into the plastic tube and
light-polymerized. All specimens were stored at 37 degrees C in water for 24 h,
and the specimens were transferred to the universal testing machine, and then
subjected to shear bond strength analysis at a crosshead speed of 1.0 mm/min.
STATISTICAL ANALYSIS USED: Data were statistically analyzed using one-way
analysis of variance and unpaired t-test at a significance level of 0.05. The
statistical analysis was performed using SPSS version 12.0.1 for Windows (SPSS
Inc., Chicago, IL, USA). RESULTS: The bond strength results were significantly
influenced by the application of bromelain enzyme. Statistically significant
differences were not demonstrated in control group and NaOCl-treated group. The
highest bond strength was seen in bromelain enzyme-treated group. CONCLUSIONS:
Within the limitations of the present study, it was concluded that removal of
unsupported collagen fiber with bromelain enzyme after acid etching results in
improved bond strength.
PMID- 26430298
TI - Comparative clinical evaluation of the efficacy of a new method for caries
diagnosis and excavation.
AB - AIM: The purpose of this study is to compare the efficiency of fluorescence-aided
caries excavation (FACE) to remove carious dentin primary teeth with that of
conventional methods. METHODS AND MATERIALS: After caries excavation was carried
out, dentin surfaces were conventionally inspected using visual tactile criteria
and 415 cavities which were classified as caries-free, re-inspected with Face
Light and caries detector dye (CDD) methods. Orange-red fluorescing areas
classified as carious dentin, as well as stained carious dentin. All the data
were recorded according to localization of the caries and determination
efficiency of the methods. X(2) test was used to compare the mean values of both
Face-Light and dye applications, while Wilcoxon test performed to evaluate the
effectiveness for each diagnostic method. RESULTS: A total of 273 patients with
415 Class II (OM/OD) cavities (1.65 +/- 0.52 teeth per patient) with carious
lesions in molar and premolar teeth, were examined. Out of 415 teeth, in 149
teeth (35.9%) no caries findings had been illustrated. While FACE detected
remaining carious or partially removed areas in 237 teeth (57.2%), CDD stained
only 29 teeth by itself (P < 0.05). CONCLUSION: In conclusion, FACE has a higher
detectability compared to visual inspection and caries detector dye in diagnosis
and removal of carious dentin.
PMID- 26430299
TI - Comparative evaluation of microshear bond strength of the caries-affected
dentinal surface treated with conventional method and chemomechanical method
(papain).
AB - BACKGROUND: There is a growing interest in chemomechanical excavation (papain) in
permanent molar teeth. There are several studies dealing with primary molar
teeth. AIM: The aim of this study was to evaluate the influence of conventional
method and Carie-care (chemomechanical method) on the microshear bond strength
(MUSBS) and the type of failure of an adhesive system to caries-affected dentin
of permanent molar teeth. MATERIALS AND METHODS: Twenty permanent molar teeth
with carious lesions extending into the dentin were selected. Through the center
of the carious lesion, teeth were sectioned mesiodistally and divided into two
groups based on the method of caries excavation (conventional and chemomechanical
method). The time required for the completion of excavation procedure was noted.
Samples were again divided into two subgroups in each according to the method of
restoration (Ketac N100 and Filtek Z350 composite). The bonded interface was
subjected to MUSBS testing in a universal testing machine. Fractured surfaces
were examined under a stereomicroscope, and representative specimens were
examined under scanning electron microscope for the type of failure. STATISTICAL
ANALYSIS: It was achieved with unpaired t-test and Kruskal-Wallis H-test at 5%
level of significance. RESULTS: The MUSBS values of Carie-care groups were
similar to that of the conventional method. The MUSBSs of resin composite were
significantly (P < 0.001) more than that of resin glass ionomer bonded
irrespective of the method of caries excavation. CONCLUSION: A papain-based
chemomechanical agent can be used safely as a method for caries removal when
employing conventional adhesive systems.
PMID- 26430300
TI - Smear layer removal efficacy of combination of herbal extracts in two different
ratios either alone or supplemented with sonic agitation: An in vitro scanning
electron microscope study.
AB - OBJECTIVES: The study aimed to evaluate the effectiveness of the combination of
two natural extracts in varying ratios for removal of smear layer either alone or
supplemented with sonic agitation. MATERIALS AND METHODS: Fifty extracted single
rooted teeth were collected, disinfected and decoronated below the cementoenamel
junction to obtain standardized root length of 10 mm. Root canals were
instrumented using rotary files at working length 1 mm short of the apex.
Specimens were divided into six groups according to the irrigation protocol as
follows: Group A - Distilled water, Group B - 17% ethylenediaminetetraacetic
acid, Group C - Herbal extracts in 1:1 ratio, Group D - Herbal extracts in 1:1
ratio supplemented with sonic agitation, Group E - Herbal extracts in 2:1 ratio,
Group F - Herbal extracts in 2:1 ratio supplemented with sonic agitation.
Specimens were longitudinally sectioned and evaluated under scanning electron
microscope for smear layer removal efficacy. Obtained scores were statistically
analyzed using one-way analysis of variance and post-hoc test. RESULTS: Among
all, Group B showed the best results followed by Group F. Remaining other groups
showed inferior outcome (P < 0.05). CONCLUSION: The combination of two extracts
in 2:1 ratio was slightly better than 1:1 ratio and the smear layer removal
efficacy was further improved when accompanied with sonic agitation.
PMID- 26430301
TI - Micro-tensile bond strength of different adhesive systems on sound dentin and
resin-based composite: An in-vitro study.
AB - AIM: To analyze the difference in the micro-tensile bond strength of specimens
made with two different adhesive systems and compare them with two homogenous
substrates. MATERIALS AND METHODS: Sixty permanent mandibular molars were mounted
in acrylic blocks and sectioned with exposed dentin surfaces. Samples were then
divided into four groups. To Group-I Adper Single Bond 2 and to Group-II Adper
Self-Etch plus bonding agents were applied. For Group-I and Group-II beams
consisted of resin composite in the upper half and dentin in the lower half. In
Group-III beams were made of only dentin. In Group-IV beams were made of only
composite. Fifteen specimens of each group were taken for the micro-tensile bond
strength test. STATISTICAL ANALYSIS: The results are analyzed using one-way
analysis of variance and Critical Difference test. RESULTS: The interface bonded
with the two adhesive systems had lower micro-tensile bond strength than those of
dentin and resin composite and the self-etching adhesive Adper Self-Etch plus had
comparable bond strength with total-etch adhesive Adper Single Bond 2.
CONCLUSION: The bond strength values for current adhesive systems cannot be
compared to the micro-tensile bond strength of dentin and resin composite, and
self-etching adhesives have comparable bond strength with total-etch adhesives.
PMID- 26430302
TI - Shrinkage, stress, and modulus of dimethacrylate, ormocer, and silorane
composites.
AB - PURPOSE: to evaluate the shrinkage, polymerization stress, elastic and bulk
modulus resulting from composites formulated by siloranes, 2(nd) generation
ormocers, and dimethacrylates. MATERIALS AND METHODS: The bonded disc method was
used to evaluate volumetric shrinkage. The polymerization stress was evaluated by
mean of the Bioman. Cylindrical specimens (5 mm thickness and 6 mm diameter) were
submitted to gradual loading. Young's and bulk modulus were obtained from the
slope of the stress/strain curve. Data were analyzed using one-way analysis of
variance and Tukey's test (5%). RESULTS: Grandio and ormocer showed significant
higher elastic and bulk modulus. Silorane presented significant lowest bulk
modulus and maximum shrinkage. Ormocer and silorane presented lower values for
the maximum rate of shrinkage. Extra-low shrinkage (ELS) composite presented the
greatest maximum shrinkage. The higher maximum rate of shrinkage was attained by
Grandio and ELS, statistically similar from each other. The silorane showed lower
values of maximum stress and maximum rate of stress. The higher values of maximum
stress were presented by ELS and Grandio, statistical similar between them.
Grandio showed the significantly greatest maximum rate of stress. CONCLUSION:
Silorane showed to promote lower shrinkage/stress among the composites, with the
lowest elastic modulus. Ormocer showed lower shrinkage/stress than methacrylates
despite of its high modulus.
PMID- 26430303
TI - Comparison of efficacy of three different desensitizing agents for in-office
relief of dentin hypersensitivity: A 4 weeks clinical study.
AB - AIM: To evaluate the effectiveness of three different pastes containing 5%
NovaMin, 8% arginine, and 15% hydroxyapatite nanoparticles (n-HA) respectively in
the treatment of dentin hypersensitivity (DH). MATERIALS AND METHODS: A 4 weeks
study was conducted on 45 adult patients with cervical abrasions leading to
hypersensitivity of two or more teeth anterior to molars. Patients were divided
into three toothpaste groups. Group I: 5% NovaMin, Group II: 8% arginine, Group
III: 15% n-HA. Sensitivity was assessed at baseline, immediately after
application and after 1-week and 4 weeks. Tactile stimuli response using a visual
analog scale and standard cold air blast using Schiff cold air sensitivity scale
were used to compare the efficacies of toothpastes after a single application.
STATISTICAL ANALYSIS: Two-way analysis of variance and post-hoc Tukey test were
used and P <= 0.05 was considered statistically significant. RESULTS: Visual
analog scale analysis: Group III and Group II showed statistically significant
reduction in DH at all-time intervals when compared with Group I. In SCA analysis
there is no statistically significant difference between Group II and Group III
immediately after application. CONCLUSION: Toothpaste containing 15% n-HA was
found to be most effective in reduction of DH after a single application up to a
period of 4 weeks followed by 8% arginine and 5% NovaMin toothpastes.
PMID- 26430304
TI - Influence of translucence/opacity and shade in the flexural strength of lithium
disilicate ceramics.
AB - BACKGROUND: Lithium disilicate ceramic system consists of glass ceramic ingots
with different grades of translucence which may influence its flexural strength.
AIMS: To assess the three-point flexural strength of the different lithium
disilicate-based ceramic ingots (IPS e.max Press/Ivoclar Vivadent) with different
levels of translucence and shade. MATERIALS AND METHODS: Six groups of ceramic
ingots were selected to represent different levels of translucence and shade
(HTA1, HTBL2, LTA2, LTB2, MO2, and HO). They measured 25 mm * 5 mm * 2 mm (n =
10), according to ISO 6872 specifications, and tested on a universal test machine
(EMIC). STATISTICAL ANALYSIS USED: A one-way analysis of variance (ANOVA) was
used (alpha = 0.05). RESULTS: The results (in MPa) were: HTA1 = 392.98; HTBL2 =
390.74; LTA2 = 390.46; LTB2 = 389.92; MO2 = 390.43; HO = 391.96. ANOVA showed no
significant difference among groups (P = 0.1528). CONCLUSIONS: Different levels
of translucence, opacity and shade of ingots did not affect their mechanical
strength, and the use of these ceramics should be guided by the esthetic demands
of each clinical situation.
PMID- 26430305
TI - An ex-vivo comparative study of root-end marginal adaptation using grey mineral
trioxide aggregate, white mineral trioxide aggregate, and Portland cement under
scanning electron microscopy.
AB - CONTEXT: Where nonsurgical endodontic intervention is not possible, or it will
not solve the problem, surgical endodontic treatment must be considered. A major
cause of surgical endodontic failures is an inadequate apical seal, so the use of
the suitable substance as root-end filling material that prevents egress of
potential contaminants into periapical tissue is very critical. AIMS: The aim of
the present ex-vivo study was to compare and evaluate the three root-end filling
materials of mineral trioxide aggregate (MTA) family (white MTA [WMTA], grey MTA
[GMTA] and Portland cement [PC]) for their marginal adaptation at the root-end
dentinal wall using scanning electron microscopy (SEM). MATERIALS AND METHODS:
Sixty human single-rooted teeth were decoronated, instrumented, and obturated
with Gutta-percha. After the root-end resection and apical cavity preparation,
the teeth were randomly divided into three-experimental groups (each containing
20 teeth) and each group was filled with their respective experimental materials.
After longitudinal sectioning of root, SEM examination was done to determine the
overall gap between retrograde materials and cavity walls in terms of length and
width of the gap (maximum) at the interface. Descriptive statistical analysis was
performed to calculate the means with corresponding standard errors, median and
ranges along with an analysis of variance and Tukey's test. RESULTS: The least
overall gap was observed in GMTA followed by PC and WMTA. While after
statistically analyzing the various data obtained from different groups, there
was no significant difference among these three groups in terms of marginal
adaptation. CONCLUSION: GMTA showed the best overall adaptation to root dentinal
wall compared to PC and WMTA. Being biocompatible and cheaper, the PC may be an
alternative but not a substitute for MTA.
PMID- 26430306
TI - Apical extrusion of debris and irrigants using ProTaper hand, M-two rotary and
WaveOne single file reciprocating system: An ex vivo study.
AB - AIMS: The purpose of this ex vivo study was to evaluate and compare the weight of
debris and volume of irrigant extruded apically from teeth using different
preparation techniques. SUBJECTS AND METHODS: Thirty extracted human mandibular
premolars with single canals and similar lengths were instrumented using hand
ProTaper F2 (25, 0.08; Dentsply Maillefer, Ballaigues, Switzerland), M-two (25,
0.06; VDW, Munich, Germany) and WaveOne Primary (25, 0.08; Dentsply Maillefer,
Ballaigues, Switzerland). Debris and irrigant extruded during instrumentation
were collected into preweighed Eppendorf tubes. The volume of the irrigant was
measured, and then the tubes were stored in an incubator at 70 degrees C for 2
days. The Eppendorf tubes were weighed to obtain the final weight when the
extruded debris was included. Three consecutive weights were obtained for each
tube. STATISTICAL ANALYSIS USED: Data were statistically analyzed by one-way
analysis of variance and Student's t-test. RESULTS: There were no statistically
significant differences among the groups. The WaveOne reciprocating system showed
the maximum amount of apical extrusion of debris and irrigant among all the
groups. The least amount of debris and irrigant was observed in ProTaper hand
instrument (P > 0.05). CONCLUSION: All instrumentation techniques were associated
with debris and irrigant extrusion.
PMID- 26430307
TI - Comparing marginal microleakage of three Bulk Fill composites in Class II
cavities using confocal microscope: An in vitro study.
AB - AIM: This study aims to evaluate and compare microleakage at the occlusal wall
and cervical wall in Class II cavities restored with one SonicFill Bulk Fill
composite and two conventional Bulk Fill composites. MATERIALS AND METHODS:
Thirty freshly extracted teeth were divided into three groups of 10 teeth each.
Standardized Class II cavities were made on the mesial and distal surfaces of
each tooth and restored using SonicFill Bulk Fill composite and two conventional
Bulk Fill composites, Tetric Evo Ceram, and X-tra fil. After storage,
thermocycling and immersion in 0.6% rhodamine dye solution specimens were
sectioned and evaluated for microleakage at the occlusal and cervical walls using
confocal microscope. STATISTICAL ANALYSIS USED: Kruskal-Wallis test, Wilcoxon
Signed-Rank test and Mann-Whitney U-test. RESULTS: The results demonstrated that
in the occlusal wall and cervical wall, SonicFill Bulk Fill composite, showed
significantly less marginal microleakage than the other groups. CONCLUSION: Based
on the results of this study, SonicFill Bulk Fill composite showed less
microleakage than the other conventional Bulk Fill composites.
PMID- 26430308
TI - Effect of intracanal medicaments on push-out bond strength of Smart-Seal system.
AB - AIM: To evaluate the effects of calcium hydroxide (CH), triple and double
antibiotic pastes (DAPs) on the bond strength of Smart-Seal obturation, C-points
with Endosequence Bio-ceramic (BC) sealer to the root canal dentin. MATERIALS AND
METHODS: Sixty-four freshly extracted single-rooted human mandibular premolars
were de-coronated and prepared using rotary Pro-taper system with full sequence
till F3. The specimens were randomly divided into a control group (without
intracanal dressing) and 3 experimental groups that received an intracanal
dressing with either CH, DAP, or triple antibiotic paste (TAP) (n = 16). The
intracanal dressing was removed after 3 weeks by rinsing with 10 mL 17%
ethylenediaminetetraacetic acid, followed by 10 mL 3% sodium hypochlorite. The
root canals were then obturated with C-points and Endosequence BC sealer. A push
out test was used to measure the bond strength between the root canal dentin and
the obturating system. The data were analyzed using two-way analysis of variance
and Tukey post-hoc test. RESULTS: The push-out bond strength values were
significantly affected by the intracanal medicaments (P < 0.001), but not by the
root canal thirds (P > 0.05). In the middle and apical third, the bond strength
of the TAP group was higher than those of the CH and DAP groups (P < 0.05).
CONCLUSIONS: The DAP and CH did not affect the bond strength of the novel
hydrophilic obutrating system. TAP improved the bond strength of Smart-Seal
system in the middle and apical thirds.
PMID- 26430309
TI - Endodontic management of a mandibular first molar with six root canal systems.
AB - Internal anatomy of pulp is complex. The first mandibular molars typically have
two roots, one mesial with two root canals and another distal root, which
contains one or two canals. A 20-year-old female patient reported with
intermittent pain and incomplete root canal treatment in left lower back region
since 1-week. Refined access cavity revealed initially two canals in mesial and
two canals in the distal root. With operating microscope and cone beam
computerized tomography, two additional canals (L-mesio-buccal and B-mesio
lingual) were identified in mesial root. One-year follow-up showed patient was
asymptomatic and complete healing of periapical radiolucency.
PMID- 26430310
TI - Resurrecting an unsalvageable lower incisor with a mono-block approach.
AB - Contemporary techniques, as well as the availability of bioactive and adhesive
materials in endodontics, have helped revivifying teeth that were deemed
hopeless. These newer materials and techniques would enable the clinician: (a) to
predictably stop microbial activity (b) to achieve a total corono-apical fluid
tight seal and (c) to strengthen mutilated teeth by obtaining intra-radicular
reinforcement through mono-block effect. This case report demonstrates the
successful treatment of a mutilated anterior tooth with the use of bioactive and
adhesive materials to obtain a total seal and mono-block effect. This article
also shows the use of a simple method in the placement of root filling cement
into the root canal.
PMID- 26430312
TI - Standardization of "In-House fatty meal" methodology for cholescintigraphy.
AB - AIM: This study was aimed at standardizing the "In-House fatty meal" methodology
in cholescintigraphy and to determine gall bladder ejection fraction (GBEF) with
this standardized meal. MATERIALS AND METHODS: This is a prospective case-control
study where 61 patients having right upper quadrant pain and postprandial
bloating and 59 healthy volunteers were included. They underwent (99m)Tc
mebrofenin fatty meal cholescintigraphy following a standard protocol. Dynamic
acquisitions over 120 min were done, with a fatty meal being given between 45-
and 60-min. Gallbladder emptying kinetics was studied by assessing the time
activity curves and calculation of GBEFs were made at 30-min, 45-min, and at 60
min and assessed. RESULTS: The GBEF at 30-min was 74.42% +/- 8.26% (mean +/-
standard deviation), at 45-min was 82.61% +/- 6.5%, and at 60-min was 89.37% +/-
4.48% in the volunteer group. The lower limit of GBEF in volunteers at 30-min was
58%, 45-min was 69%, and at 60-min was 81%. Receiver operating characteristic
(ROC) analysis showed that 30-min GBEF provided the best separation between
healthy and diseased subjects with an area under curve of 0.952 (95% confidence
interval = 0.914-0.989). The lower limit of GBEF at 30-min was 58%. CONCLUSIONS:
An in-House standard fatty meal could be a reproducible alternative to
cholecystokinin as it is well-tolerated. Based on ROC curve analysis, we propose
that 30-min GBEF provides good separation between healthy and diseased people
with this in-House fatty meal. Hence, dynamic acquisitions beyond 30-min
postingestion of the fatty meal may not be warranted.
PMID- 26430311
TI - Dimercaptosuccinic acid: A multifunctional cost effective agent for imaging and
therapy.
AB - Dimercaptosuccinic acid (DMSA) is an analog of dimercaprol used as metal
chelating moiety in variety of conditions. In nuclear medicine itself two types
of Tc-99m DMSA complexes are used, trivalent and pentavalent forms. In this
review, we have discussed the mechanism of uptake of both complexes as well as
diagnostic and therapeutic application in a clinical scenario.
PMID- 26430313
TI - Predictive value of pyramidal lobe, percentage thyroid uptake and age for
ablation outcome after 15 mCi fixed dose of radioiodine-131 in Graves' disease.
AB - PURPOSE: The purpose was to find out the efficacy of fixed 15 mCi radioactive
iodine-131 (RAI) dose and predictive values of various factors for inducing
hypothyroidism in Graves' disease (GD). MATERIALS AND METHODS: Retrospective
study conducted from January 2012 till August 2014. Patients with GD who had a
technetium-99m thyroid scan, thyroid antibodies, received fixed 15 mCi RAI and
did follow endocrine clinics for at least 6 months were selected. RAI was
considered successful if within 6 months of RAI therapy patients developed
hypothyroidism. RESULTS: Of the 370 patients with GD who had RAI during study
period, 210 (57%) qualified study criteria. Mean age of patients was 48 +/- 15
years with female: male ratio of 69:31, positive thyroid antibodies in 61%, means
thyroid uptake of 15.09 +/- 11.23%, and presence of pyramidal lobe in 40% of
total population. Hypothyroidism was achieved in 161 (77%) patients while 49
(23%) patients failed to achieve it (remained either hyperthyroid or euthyroid on
antithyroid medication). Patients who became hypothyroid were significantly
younger with higher proportion of presence of thyroid antibodies and pyramidal
lobe and lower percentage thyroid uptake than those who failed. Multiple logistic
regression analysis revealed that age (odds ratio; OR = 2.074), pyramidal lobe
(OR = 3.317), thyroid antibodies (OR = 8.198), and percentage thyroid uptake (OR
= 3.043) were found to be significant prognostic risk factors for post-RAI
hypothyroidism. Gender was found to have nonsignificant association with the
development of hypothyroidism. Receiver operating characteristic analysis
revealed age <42 years and thyroid uptake <15% as threshold values for the
development of post-RAI hypothyroidism. CONCLUSION: We conclude that fixed (15
mCi) RAI dose is highly effective in rendering hypothyroidism in patients with
GD. Age (<=42 years), thyroid uptake (<=15%) and presence of pyramidal lobe are
strong predictors of hypothyroidism and must be considered for selecting optimal
RAI dose.
PMID- 26430314
TI - Dual time point fluorodeoxyglucose positron emission tomography/computed
tomography in differentiation between malignant and benign lesions in cancer
patients. Does it always work?
AB - OBJECTIVES: Assess the added value of dual time point F-18-fluorodeoxyglucose
positron emission tomography/computed tomography (DTP F-18-FDG-PET/CT) in the
differentiation of malignant from a benign lesion in cancer patients. MATERIALS
AND METHODS: Totally, 140 F-18-FDG PET/CT scans of 60 cancer patients who
underwent DTP protocol (early whole body PET/CT [E] at 60 min [range, 45-76 min]
and delayed limited PET/CT [D] on areas of interest at 120 min [range, 108-153
min] after the tracer injection) were retrospectively reviewed. Visual and semi
quantitative analysis was performed on both early and delayed images. All
findings were confirmed by histopathology and/or at least 3 months follow-up (F
18-FDG PET/CT, CT, or magnetic resonance imaging). The result was considered true
positive (TP) if delayed standardized uptake value (SUV) of suspicious lesions
increased and confirmed to be malignant, false positive (FP) if delayed SUV
increased and confirmed to be benign, true negative (TN) if delayed SUV unchanged
or decreased and confirmed to be benign, and false negative (FN) if delayed SUV
unchanged or decreased and confirmed to be malignant. RESULTS: A total of 164
suspicious lesions were detected (20 presacral lesions, 18 lung nodules, 18
Hodgkin's disease (HD) lesions, 16 rectal lesions, 16 head and neck (H and N)
lesions, 14 hepatic lesions, 14 non-Hodgkin's lymphoma (NHL) lesions, 12
mediastinal lymph nodes (LNs), 10 focal gastric uptake, 10 soft tissue lesions, 8
breast lesions, 4 peritoneal nodule, and 4 others). Sixty-four lesions were
pathologically confirmed, and 100 lesions were confirmed based on 3-6 months
follow-up. There were 62 TP lesions, 44 FP, 58 TN and no FN results. The overall
sensitivity was 100% of DTP F-18-FDG PET/CT in detecting suspicious lesions. The
specificity was 57% in differentiating malignant from benign lesions, and the
accuracy was 73%. Positive predictive value was 59%, negative predictive value
(NPV) 100%. All hepatic lesions were TP. Accuracy in metastatic hepatic lesions
HD, presacral soft tissue, lung nodules, H, and N cancer, breast cancer, NHL and
mediastinal LN was100%, 88.8%, 80%, 78%, 75%, 75%, 71%, and 33.3%, respectively.
CONCLUSIONS: DTP F-18-FDG-PET/CT protocol does not always work in differentiation
between benign and malignant lesions. However; it has high NPV, and promising
results was noted in hepatic lesions, lymphoma, and recurrent rectal cancer.
PMID- 26430315
TI - Patterns of brown fat uptake of 18F-fluorodeoxyglucose in positron emission
tomography/computed tomography scan.
AB - Fluorodeoxyglucose (FDG) positron emission tomography (PET) has become the common
imaging modality in oncological practice. FDG uptake is seen in brown adipose
tissue in a significant number of patients. Recognizing the uptake patterns is
important for optimal FDG PET interpretation. The introduction of PET/computed
tomography (PET/CT) revolutionized PET imaging, bringing much-needed anatomical
information. Careful review and correlation of FDG PET images with anatomical
imaging should be performed to characterize accurately any lesion having high FDG
uptake.
PMID- 26430316
TI - Pictorial essay of developmental thyroid anomalies identified by Technetium
thyroid scintigraphy.
AB - Developmental anomalies and anatomic variations of the thyroid gland in the
general population with no known thyroid dysfunction usually goes unnoticed. Only
those patients with neck swellings, incidentally detected hypo or
hyperthyroidism, and those with a maternal history of hypothyroidism undergo
screening for the thyroid gland. Neck ultrasound and scintigraphic techniques are
the imaging tools routinely used to identify these anomalies. We present
interesting technetium (Pertechnetate and sestaMIBI) scintigraphic images of
adults and children who presented to our department with thyroid dysfunction
showing developmental anomalies of the thyroid.
PMID- 26430317
TI - 18F-fluorodeoxyglucose positron emission tomography/computed tomography for
primary thyroid langerhans histiocytosis: A case report and literature review.
AB - Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disease, with
an incidence rate of 4.0-5.4/1 million individuals. LCH encompasses a spectrum of
disorders with diverse clinical presentations ranging from a single organ to
multiple organ involvement. LCH rarely involves the thyroid gland. We presented a
case with LCH of thyroid gland. The patient had painless progressive neck
enlargement and then diabetes insipidus. Ultrasonic scan and magnetic resonance
imaging scan revealed nodular goiter and pituitary stalk enlargement,
respectively. Histopathological analysis revealed features of histiocytoid cells.
18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography
(PET/CT) was performed in order to rule out the presence of whole body
infiltration. 18F-FDG PET/CT also demonstrated increased uptake in the thickening
pituitary stalk and maxillofacial skin lesion, in addition to the bilateral
thyroid nodules, CT showed the left lung nodule and the skull destruction without
18F-FDG uptake. This report emphasizes the role of 18F-FDG PET/CT in multiple
organs involvement of patients with LCH.
PMID- 26430319
TI - Malignant chondroid syringoma of the pinna.
AB - Chondroid syringoma (CS) represents the cutaneous counterpart of mixed tumor
(pleomorphic adenoma) of salivary glands. The malignant counterpart of CS, termed
as "malignant CS" is a malignant eccrine neoplasm which lacks distinctive
clinical features, often delaying initial diagnosis. Unlike its benign
counterpart which often localizes in the head and neck region, malignant CS most
often encountered in the trunk and the extremities. We report a rare case of an
aggressive malignant CS of the left pinna with cervical lymph node metastasis.
Our patient, to the best of our knowledge, possibly is the first case of
malignant CS of the pinna and the fourth to arise in the head and neck region.
The diagnostic challenges with an added emphasis on the role of positron emission
tomography-computed tomography in aiding the management of this rare tumor are
discussed.
PMID- 26430318
TI - A rare tumor with unusual clinical presentation detected by positron emission
tomography-computed tomography.
AB - Primary hepatic lymphoma represents <1% of extranodal lymphoma and predominantly
seen in men older than 50 years of age. Exact etiology for these tumors is not
certain yet, but presumed to be caused by certain viruses like Epstein-Barr virus
and hepatitis C virus due to the frequent association of these viruses with
disease. Most of these tumors are diffuse large B cell non-Hodgkin lymphoma.
Direct tissue histopathology with immunochemistry may give clues about diagnosis
and prognosis up to certain extent. The rituximab-based chemotherapy is the
mainstay of therapy for these tumors; the role of radiotherapy is still not clear
but used for management for bulky tumors.
PMID- 26430320
TI - Dual thyroid ectopia-role of thyroid scintigraphy and neck ultrasonography.
AB - Ectopic thyroid tissue (ETT) is a rare developmental anomaly of the thyroid
tissue where the thyroid gland is not located in its usual position. Dual thyroid
ectopia is far rarer. This case of a 5-year-old euthyroid girl with thyroglossal
cyst was planned for surgery. Presurgical ultrasonography (USG) of the neck
followed by thyroid scintigraphy was performed. There was absent normal thyroid
gland with single ETT in neck swelling on USG. However, thyroid scintigraphy
revealed two ectopic foci of thyroid tissue; one was corresponding to neck
swelling, and other was superior to it at the base of the tongue along with
absent eutopic thyroid gland. The repeat neck USG could demonstrate the same. The
present case emphasizes that, if the thyroid gland is not visible by USG; ETT
should be evaluated with thyroid scintigraphy in case of thyroid dysgenesis.
PMID- 26430321
TI - Nodular Graves' disease with medullary thyroid cancer.
AB - Co-existence of thyroid nodules with Graves' disease has been reported in various
studies. 10-15% of such nodules harbor thyroid cancer with papillary thyroid
cancer being the commonest. Medullary thyroid cancer (MTC) in nodules associated
with Graves' disease is rare. On literature survey, we came across 11 such cases
reported so far. We report a 62-year-old female with Graves' disease who also had
a thyroid nodule that on fine-needle aspiration cytology and the subsequent
postthyroidectomy histopathological examination was reported to be MTC.
PMID- 26430322
TI - Bilateral breast uptake of radioiodine in a male patient with gynecomastia: A
case report.
AB - A 56-year-old male patient with papillary thyroid carcinoma was given radioiodine
for the treatment of persistent disease. Post radioiodine whole body scan
revealed uptake at the thyroidal region and bilateral uptake at the upper
thoracic region. Single photon emission computed tomography/computed tomography
(SPECT/CT) confirmed uptake at the left thyroid lobe, and additional symmetrical
mammary gland uptake was observed at both breasts. The patient had obesity
related gynecomastia, but he did not have any history of breast cancer, mastitis,
hyperprolactinemia, or galactorrhea. Although breast uptake of radioiodine is a
common finding in postpartum or lactating women, it is uncommon in male patients.
To our knowledge, this is the first case of a male patient with breast uptake of
radioiodine documented with SPECT/CT. SPECT/CT is useful in male patients in the
differentiation of benign breast uptake with lung metastases or axillary
metastases of thyroid cancer.
PMID- 26430323
TI - Hiatal hernia uptake of iodine-131 mimicking mediastinal metastasis of papillary
thyroid carcinoma.
AB - There are a few case reports of hiatal hernia demonstrating thoracic uptake on I
131 scintigraphy. In this case, high thyroglobulin levels in combination with
misinterpretation of I-131 uptake in the mediastinum, leaded to mismanagement of
the patient. Here we present a case of focal I-131 uptake within a hiatal hernia
initially mimicking an isolated mediastinal metastasis. There are many potential
causes of false-positive I-131 scan result. In this case, adjunctive chest
computed tomography and gastroesophageal barium study helped to elucidate the
true nature of this I-131 uptake. False-positive findings may be caused by a wide
variety of nonthyroidal carcinomas, which can concentrate radioiodine or from
skin contamination. Several organs, such as the gastric, salivary glands, renal
cyst, pericardial effusion, and ovarian can accumulate I-131. It should be borne
in mind as a potential source of false-positive whole-body I-131 imaging.
PMID- 26430324
TI - Flip-flop phenomenon in systemic sclerosis on fluorodeoxyglucose positron
emission tomography/computed tomography.
AB - Systemic sclerosis (SSc) is a rare autoimmune disease, which may affect multiple
organ systems. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission
tomography/computed tomography (PET/CT) can demonstrate the degree and anatomical
extent of involvement in the entire body and coexisting malignancies in
connective tissue diseases. We present a case of SSc with an increased 18F-FDG
uptake in the cutaneous and subcutaneous tissues even higher than the neighboring
skeletal muscles ("flip-flop phenomenon," that is, an increased 18F-FDG uptake in
the skin but a decreased 18F-FDG uptake in the skeletal muscles).
PMID- 26430325
TI - Venous thrombosis of sarcoidosis as an unusual incidental finding on 18F
fluorodeoxyglucose positron emission tomography/computed tomography.
AB - Sarcoidosis is defined as a multisystem granulomatous disorder of unknown cause.
Venous thrombosis (VT) in the sarcoidosis is rare. The routine use of 18F
fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG
PET/CT) has resulted in clinicians detecting many incidental findings, which have
proven to be clinically significant such as thrombosis. Here, we present a case
with VT of sarcoidosis in the inferior vena cava and portal vein as an unusual
incidental finding on 18F-FDG PET/CT.
PMID- 26430326
TI - Role of fluorine-18 fluorodeoxyglucose positron emission tomography in a case of
renal cell carcinoma to differentiate tumor thrombus from bland thrombus.
AB - Tumor thrombus is a rare complication of many solid tumors. We present a case of
renal cell carcinoma whose baseline contrast-enhanced computerized tomography
(CT) revealed an heterogeneously enhancing mass in the upper half of right kidney
with tumor thrombus in the right renal vein extending to suprarenal inferior vena
cava (IVC), crossing the cavoatrial junction and reaching up to the right atrium
(Grade IV). Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography
(PET)/CT imaging revealed large irregular right renal mass, hypermetabolic tumor
thrombus extending from the right renal vein to suprarenal IVC reaching up to the
right atrium. There was no FDG uptake noted in the infrarenal IVC and bilateral
iliofemoral venous thrombi. Thus, 18F-FDG PET/CT was not only helpful in the
staging, but was also helpful in differentiating tumor thrombus from bland
thrombus in our patient.
PMID- 26430327
TI - Unusual case of hepatic metastasis in follicular thyroid carcinoma detected using
I-131 whole body scintigraphy and single-photon emission computerized
tomography/computerized tomography.
AB - Papillary and follicular thyroid carcinomas, together known as differentiated
thyroid carcinomas (DTC), are among the most curable of cancers. Distant
metastases are rare events at the onset of DTC. Among these presentations,
metastasis to the liver is even more unusual. Only 11 cases of DTC with liver
metastasis were previously reported in the literature. We present a 55-year-old
male on Iodine-131 whole body scintigraphy showed intense uptake in thyroid bed,
metastasis in both lungs and right lobe of the liver. Radioiodine concentration
in liver metastases made him amenable to high-dose radioiodine therapy patient.
PMID- 26430329
TI - Lung or liver: An imaging dilemma on Tc-99m macroaggregated albumin lung
perfusion scintigraphy.
AB - We present a 10-year-old boy having the bronchiectasis who was subjected to lung
perfusion scintigraphy before lung resection surgery to assess the lung
parenchymal function. It revealed unusual tracer distribution in right upper body
that was mimicking to be liver. It was unusual unless there were some shunts
bypassing the lung uptake or faulty radiopharmaceutical preparation. However by
bringing down the image window, it became clear that radiopharmaceutical
distribution was in thorax only correlating with lung uptake, and not in the
liver. Corresponding X-ray chest and computed tomography thorax demonstrated
multiple cystic lesions in left lung parenchyma.
PMID- 26430328
TI - Dystrophic calcification in muscles of legs in calcinosis, Raynaud's phenomenon,
esophageal dysmotility, sclerodactyly, and telangiectasia syndrome: Accurate
evaluation of the extent with (99m)Tc-methylene diphosphonate single photon
emission computed tomography/computed tomography.
AB - We present the case of a 35-year-old man with calcinosis, Raynaud's phenomenon,
esophageal dysmotility, sclerodactyly and telangiectasia variant scleroderma who
presented with dysphagia, Raynaud's phenomenon and calf pain. (99m)Tc-methylene
diphosphonate bone scintigraphy was performed to identify the extent of the
calcification. It revealed extensive dystrophic calcification in the left thigh
and bilateral legs which was involving the muscles and was well-delineated on
single photon emission computed tomography/computed tomography. Calcinosis in
scleroderma usually involves the skin but can be found in deeper periarticular
tissues. Myopathy is associated with a poor prognosis.
PMID- 26430330
TI - Accurately localizing the thyroid tissue in mature cystic teratoma of ovary by
single-photon emission computerized tomography/computerized tomography.
AB - A 30-year-old woman with hyperthyroidism was admitted to hospital. Although
increased thyroid function was found, the gland was normal in ultrasonography
(USG). Additionally, thyroid iodine uptake and Tc-99m pertechnetate scintigraphy
was normal. Abdomen USG detected a cystic pelvic mass in left ovary. A whole-body
scan was performed 48 hours after oral ingestion of 29.6 MBq (0.8 mCi) I-131
(iodine-131) revealed a round structure located to the left lower abdomen. Iodine
uptake was detected in this cyst which was compatible with functional thyroid
tissue demonstrated by SPECT/CT. The patient was underwent surgical operation and
histopathology confirmed mature cystic teratoma. Accurate localization and
depiction of thyroid tissue in ovary mass was provided with SPECT/CT.
PMID- 26430331
TI - A rare case mimicking positron emission tomography/computed tomography mismatch:
Hepatic subcapsular hematoma.
AB - Subcapsular collections of bile, air or blood in the liver have been described
following transhepatic procedures due to the leakage of bile and blood from the
percutaneous puncture at the surface of the liver. Herein we presented the
subcapsular collection led to a mismatch between functional and anatomical
boundaries of the liver.
PMID- 26430332
TI - Seminal vesicle metastasis from carcinoma lung: A very unusual metastatic site
detected with (18)F-Fluorodeoxyglucose positron emission tomography/computed
tomography.
PMID- 26430333
TI - Splenic metastasis of breast cancer: A rare metastatic site depicted on fluorine
18 fluorodeoxyglucose positron emission tomography/computed tomography.
PMID- 26430334
TI - Measuring family satisfaction in an Indian Intensive Care Unit.
PMID- 26430335
TI - Critical care: Are we customer friendly?
AB - OBJECTIVE: Assessing and enhancing family satisfaction are imperative for the
provision of comprehensive intensive care. There is a paucity of Indian data
exploring family's perception of Intensive Care Unit (ICU) patients. We wanted to
explore family satisfaction and whether it differed in families of patients
admitted under intensivists and nonintensivists in our semi-open ICU.
METHODOLOGY: We surveyed family members of 200 consecutive patients, between
March and September 2009 who were in ICU for >3 days. An internationally
validated family satisfaction survey was adapted and was administered to a family
member, on day 4 of the patient's stay. The survey consisted of 15 questions in
five categories - patient care, medical counseling, staff interaction, visiting
hours, and facilities and was set to a Likert scale of 1-4. Mean, median, and
proportions were computed to describe answers for each question and category.
RESULTS: A total of 515 patients were admitted during the study period, of which
200 patients stayed in the ICU >3 days. One family member each of the 200
patients completed the survey with 100% response rate. Families reported the
greatest satisfaction with patient care (94.5%) and least satisfaction with
visiting hours (60.5%). Chi-square tests performed for each of the five
categories revealed no significant difference between satisfaction scores of
intensivists and nonintensivists' patients. CONCLUSION: Family members of ICU
patients were satisfied with current care and communication, irrespective of
whether they were admitted under intensivists or nonintensivists. Family members
preferred open visiting hours policy than a time limited one.
PMID- 26430336
TI - Calcium homeostasis disorder during and after neonatal extracorporeal membrane
oxygenation.
AB - BACKGROUND AND AIMS: Extracorporeal membrane oxygenation (ECMO) is used during
pediatric resuscitation in case of refractory hypoxemia or septic shock under
maximum therapy. Previous studies describe calcium homeostasis dysregulation. The
aim of this study was to confirmed of calcium homeostasis dysregulation in
neonates under ECMO and supposed news explanation. SUBJECTS AND METHODS: From
November 2012 to July 2013, we performed a prospective single center
observational study. Eleven neonatal patients were included. Blood was obtained
before and during ECMO (day 7, 14 and 21) for parathyroid hormone (PTH), protein
adjusted serum calcium, ionized calcium, magnesium, and calcitriol levels. All
surviving patients underwent a consultation up to 6 months after ECMO weaning.
RESULTS: During ECMO PTH was inadequately high with normal serum calcium on day 7
(PTH: 73.54 +/- 40 ng/l; calcemia: 2.33 +/- 0.21 mmol/l), day 14 (PTH: 57.63 +/-
29.57 ng/l; calcemia: 2.44 +/- 0.43 mmol/l) and day 21 (PTH: 54.93 +/- 8.43 ng/l;
calcemia: 2.13 +/- 0.09 mmol/l). The absence of correlation between serum calcium
and PTH levels seem to confirm the dysregulation of PTH - serum calcium
metabolism during ECMO. Six months after ECMO weaning, we noticed hypercalcemia
with normal PTH. CONCLUSIONS: We confirmed the existence of severe disturbances
of calcium homeostasis in neonates on ECMO and supposed the possible damage of
calcium regulation. We did not succeed in finding clear explanations of these
disturbances.
PMID- 26430337
TI - Assessing nutrition in the critically ill elderly patient: A comparison of two
screening tools.
AB - CONTEXT: Few malnutrition screening tests are validated in the elderly Intensive
Care Unit (ICU) patient. AIM: Having previously established malnutrition as a
cause of higher mortality in this population, we compared two screening tools in
elderly patients. SUBJECTS AND METHODS: For this prospective study, 111
consecutive patients admitted to the ICU and > 65 years underwent the
Malnutrition Universal Screening Tool (MUST), and the Geriatric Nutrition Risk
Index (GNRI) screening tests. STATISTICAL ANALYSIS: Standard definition of
malnutrition risk was taken as the gold standard to evaluate the sensitivity,
specificity and predictive values of the tools. The k statistic was calculated to
measure the agreement between the tools. The Shrout classification was used to
interpret its values. RESULTS: The mean age of the patients screened was 74.7 +/-
8.4 (65-97 years). The standard definition, MUST and GNRI identified 52.2%,
65.4%, and 64.9% to be malnourished, respectively. The sensitivity and
specificity of the tests were 96.5% computed tomography (CI) (87.9-99.5%) and
72.3% CI (57.5-84.5%) for MUST and 89.5% CI (75.2-96.7%) and 55.0% CI (75.2
96.9%) for GNRI, respectively. Screening was not possible by GNRI and MUST tool
in 31% versus 4% of patients, respectively. The agreement between the tools was
moderate for Standard-MUST k = 0.65 and MUST-GNRI k = 0.60 and fair for Standard
GNRI k = 0.43. CONCLUSIONS: The risk of malnutrition is high among our patients
as identified by all the tools. Both GNRI and MUST showed a high sensitivity with
MUST showing a higher specificity and greater applicability.
PMID- 26430338
TI - Neonatal mechanical ventilation: Indications and outcome.
AB - BACKGROUND AND AIMS: Decreasing mortality in sick and ventilated neonates is an
endeavor of all neonatologists. To reduce the high mortality in this group of
neonates, identification of risk factors is important. This study was undertaken
to find out the indications of ventilation and complications in ventilated
neonates and also study possible predictors of outcome. SUBJECTS: Age <1-month;
mechanically ventilated; not having suspected metabolic disorders or congenital
anomalies; excluding postoperative patients. METHODS: Neonates consecutively put
on mechanical ventilation during the study period (October 2011 to November 2013)
enrolled. Primary disease of the neonates along with complications present
listed. Clinical and laboratory parameters analyzed to find the predictors of
mortality. RESULTS: Total 300 neonates were ventilated. 52% were male. Mean age,
weight, and gestational age were 21 +/- 62 h, 2320 +/- 846.2 g, and 35.2 +/- 4.9
weeks, respectively. 130 (43%) neonates died. Respiratory distress syndrome (RDS)
(31.1%), sepsis (22.7%), and birth asphyxia (18%) were the most common
indications for ventilation. Mortality in ventilated patients with sepsis,
pneumonia, RDS or birth asphyxia was 64.7%, 60%, 44.6%, and 33.3%, respectively.
Weight <2500 g, gestation <34 weeks, initial pH <7.1, presence of sepsis, apnea,
shock, pulmonary hemorrhage, hypoglycemia, neutropenia, and thrombocytopenia were
significantly associated with mortality (P < 0.05). Resuscitation at birth,
seizures, intra ventricular hemorrhage, pneumothorax, ventilator-associated
pneumonia, PO2, or PCO2 did not have a significant association with mortality. On
logistic regression, gestation <34 weeks, initial pH <7.1, pulmonary hemorrhage,
or shock were independently significant predictors of mortality. CONCLUSIONS:
Weight <2500 g, gestation <34 weeks, initial arterial pH <7.1, shock, pulmonary
hemorrhage, apnea, hypoglycemia, neutropenia, and thrombocytopenia were
significant predictors of mortality in ventilated neonates.
PMID- 26430339
TI - Critical care medicine for emerging Middle East respiratory syndrome: Which point
to be considered?
AB - The Middle East respiratory syndrome (MERS) is a new emerging respiratory tract
infection. This coronavirus infection is firstly reported from the Middle East,
and it becomes threat for the global public health at present due to its
existence in a remote area such as USA and Korea. The concern on the management
of the patients is very important. Since most of the patients can develop severe
respiratory illness and critical care management is needed, the issue on critical
care for MERS is the topic to be discussed in critical medicine.
PMID- 26430340
TI - Use of metabolic monitors in a multidisciplinary Intensive Care Unit: A
prospective pilot study of 20 patients.
AB - INTRODUCTION: Caloric intake of critically ill patients are usually calculated
using predictive equations. Recent advances in gas exchange measurements have the
potential to estimate energy expenditure at the bedside and at different time
periods. MATERIALS AND METHODS: Energy needs of critically ill patients were
estimated over a period of 3 months using simplistic formula of 25 kcal/kg/day
estimated energy expenditure (EEE), Harris-Benedict equation (HBE) (Basal energy
expenditure [BEE]) and M-COVXTM metabolic monitor resting energy expenditure
(REE) on day 4 of Intensive Care Unit (ICU) admission. Calculations based on HBE
were taken as standard, and percentage errors (PE) were calculated for each
patient for values derived from simplistic formula and metabolic monitor.
Adequacy of nutritional intake in ICU was also assessed. RESULTS: Metabolic
monitor could be used in only 20/70 patients. The mean age of patients was 40
years, 65% were males, and average body mass index was 23.69 kg/m(2).
Intermittent intolerance to feeds was reported in 50%. Values of REE and EEE were
greater than BEE in 70% of patients. A significant difference was reported in
values of PE of <=20% and >=30%; P = 0.0003 and 0.0001, respectively estimated
using REE and EEE. CONCLUSIONS: It is not feasible to use metabolic monitors in
all patients. Variability in readings is large and further studies are needed to
establish the validity of its measurements. Calculations using simplistic
formulas are much closer to values obtained using HBE.
PMID- 26430341
TI - Targeted temperature management: Current evidence and practices in critical care.
AB - Targeted temperature management (TTM) in today's modern era, especially in
intensive care units represents a promising multifaceted therapy for a variety of
conditions. Though hypothermia is being used since Hippocratic era, the renewed
interest of late has been since early 21(st) century. There have been multiple
advancements in this field and varieties of cooling devices are available at
present. TTM requires careful titration of its depth, duration and rewarming as
it is associated with side-effects. The purpose of this review is to find out the
best evidence-based clinical practice criteria of therapeutic hypothermia in
critical care settings. TTM is an unique therapeutic modality for salvaging
neurological tissue viability in critically ill patients viz. Post-cardiac
arrest, traumatic brain injury (TBI), meningitis, acute liver failure and stroke.
TTM is standard of care in post-cardiac arrest situations; there has been a lot
of controversy of late regarding temperature ranges to be used for the same. In
patients with TBI, it reduces intracranial pressure, but has not shown any
favorable neurologic outcome. Hypothermia is generally accepted treatment for
hypoxic ischemic encephalopathy in newborns. The current available technology to
induce and maintain hypothermia allows for precise temperature control. Future
studies should focus on optimizing hypothermic treatment to full benefit of our
patients and its application in other clinical scenarios.
PMID- 26430342
TI - Anaphylaxis to scorpion antivenin and its management following envenomation by
Indian red scorpion, Mesobuthus tamulus.
AB - Mesobuthus tamulus is an Indian red scorpion that is responsible for numerous
cases of scorpion stings in the Indian subcontinent. Antivenin, vasodilators, and
benzodiazepines are medications of choice in the treatment of scorpion bites.
Adverse reactions such as anaphylaxis to antivenin have been infrequently
described in the literature. We, herein, present a case of a 42-year-old man
stung by Indian red scorpion while gardening at home in India, who presented with
extreme pain at the sting site and signs of cardio-toxicity. He was treated with
scorpion antivenin and vasodilators but developed anaphylaxis to antivenin. We
discuss management strategies. Anaphylaxis to antivenin should be on the
differential during management of scorpion bites because classical signs of
anaphylaxis may be absent.
PMID- 26430343
TI - An unusually dry story.
AB - We present a middle-aged woman with a prior history of central nervous system
(CNS) demyelinating disorder who presented with an acute onset quadriparesis and
respiratory failure. The evaluation revealed distal renal tubular acidosis with
hypokalemia and medullary nephrocalcinosis. Weakness persisted despite potassium
correction, and ongoing evaluation confirmed recurrent CNS and long-segment
spinal cord demyelination with anti-aquaporin-4 antibodies. There was no history
of dry eyes or dry mouth. Anti-Sjogren's syndrome A antigen antibodies were
elevated, and there was reduced salivary flow on scintigraphy. Coexistent
antiphospholipid antibody syndrome with inferior vena cava thrombosis was also
found on evaluation. The index patient highlights several rare manifestations of
primary Sjogren's syndrome (pSS) as the presenting features and highlights the
differential diagnosis of the clinical syndromes in which pSS should be
considered in the Intensive Care Unit.
PMID- 26430344
TI - Crimean-Congo hemorrhagic fever: An emerging threat for the intensivist.
AB - We present the case of a 55-year-old female, who presented with 15 days of fever
with rash, pancytopenia, and altered behavior. She was investigated for routine
causes of fever with rash and multi organ dysfunction and treated for the same.
As she tested negative for all routine causes of such an illness and did not show
improvement to therapy, she was investigated for Crimean-Congo hemorrhagic fever
and tested positive for the same. She was started on ribavirin, but eventually
succumbed to her illness. This disease has rarely been reported from the Northern
India and we need to have high clinical suspicion for this deadly disease so that
appropriate therapy can be started in time for the patient and prophylaxis given
to all inadvertently exposed.
PMID- 26430345
TI - Difficult airway management from Emergency Department till Intensive Care Unit.
AB - We report a case of "can ventilate but can't intubate" situation which was
successfully managed in the Emergency Department and Intensive Care Unit by the
use of ProSeal laryngeal mask airway and Frova Intubating Introducer as bridging
rescue devices. Use of appropriate technique while strictly following the
difficult airway algorithm is the mainstay of airway management in unanticipated
difficult airway situations. Although the multiple airway devices were used but
each step took not more than 2 min and "don't struggle, skip to the next step
principle" was followed. With the availability of many advanced airway management
tools, the intensivists should have a training and experience along with
preparedness in order to perform such lifesaving airway managements.
PMID- 26430346
TI - Should intensivist do routine abdominal ultrasound?
AB - Roundworm infestation is common in tropical climate population with a low
socioeconomic status. We describe a case of a young male with polytrauma accident
who presented with small bowel dysfunction with a high gastric residual volume
during enteral feeding. While searching the etiology, the intensivist performed
bedside abdominal ultrasound (USG) as a part of whole body USG screening along
with clinical examination using different frequency probes to examine bowel
movement and ultimately found ascariasis to be the cause. This case report will
boost up the wide use of bedside USG by critical care physicians in their patient
workup.
PMID- 26430347
TI - Severe masseter spasms in a Rett syndrome during rapid sequence intubation: A
succinylcholine severe side effect.
PMID- 26430348
TI - System of adverse drug reactions reporting: What, where, how, and whom to report?
PMID- 26430349
TI - Factors for early death in rabies- the bitter truth.
PMID- 26430350
TI - Novel Use of Proteomic Profiles in a Convex-Hull Ensemble Classifier to Predict
Gynecological Cancer Patients' Susceptibility to Gastrointestinal Mucositis as
Side Effect of Radiation Therapy.
AB - BACKGROUND: Whole-pelvis radiation therapy is common practice in the post
surgical treatment of cervical and endometrial cancer. Gastrointestinal mucositis
is an adverse side effect of radiation therapy, and is a primary concern in
patient management. We investigate whether proteomic information obtained from
blood samples drawn from patients scheduled to receive radiation therapy for
gynecological cancers could be used to predict which patients are most
susceptible to radiation-induced gastrointestinal mucositis, in order to improve
the individualization of radiation therapy. METHODS: We use 132 proteins measured
on 17 gynecological cancer patients in a convex-hull-based, selective-voting
ensemble classifier to classify each patient into one of two classes: patients
who would not (class 1) or would (class 2) develop gastrointestinal mucositis. We
employ 20 repetitions of 10-fold cross-validation to measure classification
accuracy. RESULTS: We achieved a 95% confidence interval on average prediction
accuracy of (0.711, 0.771) using pre-radiation proteomic profiles to predict
which patients would experience gastrointestinal mucositis. Pathway analysis of
the 12 most prominent proteins indicated that they could be assembled into a
single interaction network with direct associations. The function associated with
the highest number of these 12 proteins was cell-to-cell signaling and
interaction. CONCLUSIONS: Pre-radiation proteomic profiles have the potential to
classify cervical/endometrial cancer patients with high accuracy as to their
susceptibility to gastrointestinal mucositis following radiation therapy. Further
study of the network of 12 identified proteins is warranted with a larger patient
sample to confirm that these proteins are predictive of gastrointestinal
mucositis in this patient population.
PMID- 26430351
TI - Cultural Difference in Conflict Management Strategies of Children and Its
Development: Comparing 3- and 5-Year-Olds Across China, Japan, and Korea.
AB - Research Findings: The purpose of this study was to examine differences in the
development of conflict management strategies, focusing on 3- and 5-year-olds,
through a comparison of 3 neighboring Asian cultures, those of China (n = 114),
Japan (n = 98), and Korea (n = 90). The dual concern model of conflict management
was adopted to probe which strategy children would prefer to use in 2
hypothetical conflict situations. Results indicated that, first, for
disagreement, 3-year-olds in the 3 countries equally preferred the dominating
strategy. For competition for resources, 3-year-olds differed in their strategy
preference across all cultures. Second, the observed strategy preference of 3- to
5-year-old children in this study was more or less different from that of older
schoolchildren, regardless of culture. Practice or Policy: These findings suggest
the significance of the context, the complexity of the phenomenon of the
development of cultural differences, and the significance of cohort sampling.
PMID- 26430352
TI - Spatial Moran Models I. Stochastic Tunneling in the Neutral Case.
AB - We consider a multistage cancer model in which cells are arranged in a d
dimensional integer lattice. Starting with all wild-type cells, we prove results
about the distribution of the first time when two neutral mutations have
accumulated in some cell in dimensions d >= 2, extending work done by Komarova
[12] for d = 1.
PMID- 26430353
TI - Fingering in Stochastic Growth Models.
AB - Motivated by the widespread use of hybrid-discrete cellular automata in modeling
cancer, two simple growth models are studied on the two dimensional lattice that
incorporate a nutrient, assumed to be oxygen. In the first model the oxygen
concentration u(x, t) is computed based on the geometry of the growing blob,
while in the second one u(x, t) satisfies a reaction-diffusion equation. A
threshold theta value exists such that cells give birth at rate beta(u(x, t) -
theta)+ and die at rate delta(theta - u(x, t)+. In the first model, a phase
transition was found between growth as a solid blob and "fingering" at a
threshold thetac = 0.5, while in the second case fingering always occurs, i.e.,
thetac = 0.
PMID- 26430354
TI - Risk Assessment's New Era, Part 3: Vision of the AIHA(r) Risk Assessment
Committee.
PMID- 26430355
TI - Relationship between School Administrators' Reports of Parental Involvement in
School and Students' Substance Use: A National Study.
AB - This study examines the relationship between student substance use and school
level parental involvement as reported by administrators. Questionnaires were
administered to school administrators and 111,652 students in 1,011 U.S. schools.
Hierarchical logistic regression analyses conducted on 1998-2003 data from
students and administrators indicate significantly lower prevalence of alcohol
use among 8th graders in schools where administrators reported high parental
involvement. Overall, administrators' reports of high parental involvement were
unrelated to prevalence of substance use among 10th graders, and were associated
with higher prevalence of alcohol use among 12th-graders. Implications and
limitations are discussed, along with suggestions for future research.
PMID- 26430356
TI - The effect of implant angulation and splinting on stress distribution in implant
body and supporting bone: A finite element analysis.
AB - OBJECTIVE: The aim of this study was to investigate the influence of implant
crown splinting and the use of angulated abutment on stress distribution in
implant body and surrounding bone by three-dimensional finite element analysis.
MATERIALS AND METHODS: For this study, three models with two implants at the site
of mandibular right second premolar and first molar were designed (1): Both
implants, parallel to adjacent teeth, with straight abutments (2): Anterior
implant with 15 mesial angulations and posterior implant were placed parallel to
adjacent tooth, (3): Both implants with 15 mesial angulations and parallel to
each other with 15 degrees angulated abutments. Restorations were modeled in two
shapes (splinted and nonsplinted). Loading in tripod manner as each point 50 N
and totally 300 N was applied. Stress distribution in relation to splinting or
nonsplinting restorations and angulations was done with ABAQUS6.13. RESULTS:
Splinting the restorations in all situations, led to lower stresses in all
implant bodies, cortical bone and spongy bone except for the spongy bone around
angulated first molar. Angulated implant in nonsplinted restoration cause lower
stresses in implant body and bone but in splinted models more stresses were seen
in implant body in comparison with straight abutment (model 2). Stresses in
nonsplinted and splinted restorations in cortical bone of angulated molar region
were more than what was observed in straight molar implant (model 3). CONCLUSION:
Implant restorations splinting lead to a better distribution of stresses in
implant bodies and bone in comparison with nonsplinted restorations, especially
when the load is applied off center to implant body. Angulations of implant can
reduce stresses when the application of the load is in the same direction as the
implant angulation.
PMID- 26430357
TI - The influence of type 2 diabetes mellitus on salivary matrix metalloproteinase-8
levels and periodontal parameters: A study in an Indian population.
AB - OBJECTIVE: Although many studies reported more severe periodontal disease and the
existing proinflammatory conditions in patients with diabetes but only few have
examined the effect of type 2 diabetes mellitus (DM) on salivary matrix
metalloproteinase-8 (MMP-8) level and other periodontal parameters. This study
aims to evaluate the effect of type 2 DM on salivary MMP-8 levels and periodontal
parameters, which might be useful in monitoring periodontal disease in diabetes.
MATERIALS AND METHODS: A total of 90 subjects were selected for the study and
were divided into three groups: Group I included 30 healthy subjects; Group II
included 30 subjects without type 2 DM but with chronic periodontitis, and Group
III included 30 subjects with type 2 DM and chronic periodontitis. Periodontal
parameters such as plaque index (PI), gingival index (GI), pocket probing depth
(PPD), and clinical attachment level (CAL) were taken. The salivary MMP-8 level
was estimated by Quantikine Human total MMP-8 immunoassay kit using ELISA method.
RESULTS: The mean value of the salivary MMP-8 of Group III was highest followed
by Group II and Group I, the least. The other periodontal parameters PI, GI, PPD,
CAL, was comparatively highest for Group III. CONCLUSION: This study suggests
that diabetes is associated with an increased prevalence, extent, and severity of
periodontitis. Furthermore, the increased levels of MMP-8 indicate the influence
of diabetes on their salivary concentration.
PMID- 26430358
TI - Relationship between periodontal status and degree of visual impairment in
institutionalized individuals.
AB - OBJECTIVE: Periodontal disease is a set of inflammatory infections that affect
the supporting structures of the dentition. Patients with visual impairment (VI)
may have more difficulty in cleaning and maintaining oral health. The purpose of
this study was to investigate the possible relationship between periodontal
status and degree of VI in institutionalized individuals. MATERIALS AND METHODS:
Fifty-two visually impaired individuals were included in this cross-sectional
study. The periodontal parameters assessed were clinical attachment level (CAL),
probing depth (PD), and visible plaque index. The degree of VI was established
as: Group 1 (mild or moderate VI), Group 2 (severe or profound VI), and Group 3
(completely blind); and the types of VI were considered as congenital and
acquired. Fisher's exact, Kruskal-Wallis, Mann-Whitney, and Spearman correlation
coefficient test were used. The level of significance was set at 5%. RESULT: Only
plaque index was higher on proximal surfaces of subjects with mild/moderate VI
when compared to the other degrees of VI (P = 0.01). Furthermore, we observed
higher values for interproximal CAL (P = 0.01), total PD (P = 0.04), and
interproximal PD in subjects with acquired VI when compared to subjects with
congenital VI (P = 0.01). CONCLUSIONS: These findings suggest that periodontal
status may be more related to the type of disability than with the degree of VI.
Acquired VI people presented a worse periodontal health than the group with
congenital VI.
PMID- 26430359
TI - Evaluation of stress distributions in peri-implant and periodontal bone tissues
in 3- and 5-unit tooth and implant-supported fixed zirconia restorations by
finite elements analysis.
AB - OBJECTIVE: In this study, it is aimed to compare the distribution of stress on
periodontal and peri-implant bone tissues in 3- and 5-unit-dental and implant
supported zirconia restorations using finite element analysis. MATERIALS AND
METHODS: Stress distribution formed in periodontal and peri-implant bone tissues
as a result of chewing forces was analyzed in dental and implant-supported three
dimensional (3D) finite element models of zirconia restoration with 5-unit placed
on the numbers of 43, 44, 45, 46, and 47 and with 3-unit placed on the number of
45, 46, and 47. Four different loading conditions were used. 200 N force was
applied in 30 degrees from the buccal inclination of number 43, 45, and 47
restorations separately and totally 850 N force was applied in 30 degrees from
the buccal inclination of whole restoration. The study was performed through
static nonlinear analysis with the 3D finite element analysis method. RESULTS:
Stress accumulation in bone tissues in the tooth-supported model was found less
than in implant-supported models. Stress accumulation was observed in the
cervical portion of the implant in implant-supported models, and stress
accumulation was observed surrounding bone of roots in tooth-supported models.
The highest stress values were occurred in 5 unit implant-supported model in all
loadings. CONCLUSION: In posterior restorations increased in the number of
supported teeth and implant can reduce the destructive forces on periodontal and
peri-implant bone tissues and may allow longer period retention of the
restorations in the mouth.
PMID- 26430360
TI - Effect of dietary combinations on plaque pH recovery after the intake of
pediatric liquid analgesics.
AB - OBJECTIVES: To study the effect of water, halloumi cheese and sugar-free (SF)
chewing gum on plaque pH recovery after the intake of sweetened PLAs. SETTINGS
AND DESIGN: A randomized clinical trial was conducted on 17 children (10 females,
7 males) aged 11-12 years with DFT/dft of more than 3. MATERIALS AND METHODS:
Each volunteer tested paracetamol and ibuprofen suspension alone or followed with
water, halloumi cheese or SF gum, as well as 10% sucrose and 10% sorbitol as
controls. Plaque pH was measured using the sampling method before and after 5,
10, 15, 20, 30 min of ingestion. STATISTICAL ANALYSIS: Statistical analysis was
performed using analysis of variance followed by least significant difference
test to assess minimum pH (min pH), maximum pH drop (DeltapH), and the area under
baseline pH, and P value was set as 0.05. RESULTS: Both ibuprofen and paracetamol
were not significantly different from 10% sucrose in terms of min pH, DeltapH,
and area under baseline pH except for min pH of ibuprofen (P = 0.034). Water and
halloumi cheese did not have a significant effect on plaque pH recovery after the
intake of both analgesics as min pH, DeltapH, and area under baseline pH were
similar to 10% sucrose except for min pH of ibuprofen + water (P = 0.048).
However, plaque pH variables after chewing SF gum for 20 min were similar to 10%
sorbitol. CONCLUSION: Chewing SF gum immediately after the intake of sweetened
PLAs for 20 min restores plaque pH and could be recommended as a complementary
aid in caries prevention.
PMID- 26430361
TI - Shaping ability of reciprocating single-file and full-sequence rotary
instrumentation systems in simulated curved canals.
AB - OBJECTIVE: The purpose of this study was to evaluate the shaping ability of three
nickel-titanium systems in simulated curved canals. MATERIALS AND METHODS: Sixty
simulated canals were prepared to apical size 25 with Reciproc, S5, and twisted
file (TF) instruments. Standardized pre and postoperative images were taken using
a digital camera, were superimposed and aberrations were recorded. Material
removal was measured at five points: The canal orifice, halfway to the orifice,
beginning of the curve, the apex of the curve, and end-point. The data were
analyzed using Kolmogorov-Smirnov, analysis of variance, and Tukey tests.
RESULTS: The mean total width of the prepared canals in the Reciproc group was
greater than the TF and S5 groups at halfway to the orifice, the beginning of the
curve, the apex of the curve, and the end-point (P < 0.05). Mean absolute
transportation was always <0.16 mm; however, significant differences occurred
between the three systems at the orifice, halfway to the orifice, and the
beginning of the curve (P < 0.05). TF created minimal absolute transportation at
halfway to the orifice and the beginning of the curve, and greater absolute
transportation at the orifice compared with the Reciproc and S5 instruments.
However, the difference between the S5 and TF groups was not statistically
significant at halfway to the orifice (P > 0.05). CONCLUSIONS: Under the
conditions of the study, Reciproc produced widest canal shapes. TF provided more
centered apical preparation and maintained the original canal shape well.
PMID- 26430362
TI - Pleasantness of facial profile and its correlation with soft tissue cephalometric
parameters: Perception of orthodontists and lay people.
AB - OBJECTIVE: This study was aimed to evaluate the perception of orthodontists and
of lay people about the facial profile and its possible correlation with
cephalometrics parameters. MATERIALS AND METHODS: A total of 20 evaluators were
divided into two groups (10 orthodontists and 10 people with no relation to such
area - lay people). They were asked to evaluate the photographs of 25 young males
and of 25 young females, aged 17-24-year-old (mean age of 22.3 years, standard
deviation 2.41 years). Photographs were randomly arranged in a photo album. The
evaluators rated each photograph by means of a scale ranging from "good" to
"deficient" based on the pleasantness of their facial profile. Nasolabial angle,
Holdaway's H-line and the distance from H-line to nose tip were measured, in
order to verify a possible relation between these soft tissue profile
cephalometric measurements and the subjective ratings. RESULTS: The kappa
statistics test showed a concordance of 0.23 among orthodontists and 0.24 among
lay people. Regarding the perception of orthodontists and lay people on facial
profile, no significant divergence could be detected. For the correlation between
cephalometric parameters and subjective ratings, there was a statistically
significant correlation between the measures H and H-nose and the rating ascribed
to the profile. CONCLUSIONS: It was concluded that smaller the difference from
the normal cephalometric pattern, the higher was the rating given to the profile,
demonstrating an important relation between subjective and objective criteria.
PMID- 26430363
TI - The prevalence and consequences of burnout on a group of preclinical dental
students.
AB - OBJECTIVE: The aim of this study is to investigate the prevalence of burnout
among a group of Turkish preclinical dental students, to compare the level of
burnout and to determine the consequences in structural equation model. MATERIALS
AND METHODS: Preclinical dental students (n = 329, 50.5% of females and 49.5% of
males) aged between 18 and 24 took part in the study. Maslach burnout inventory
student version, academic satisfaction scale, and personal information sheet were
used to gather data. Pearson correlation analyses, t-test, and one-way ANOVA were
used for statistical analysis. The proposed theoretical model was tested via
observed variable path analysis using maximum likelihood parameter estimation
with AMOS 7.0. RESULTS: About 22.3% of students had high level of emotional
exhaustion, 16.7% of students had high level of cynicism, and 17.9% of students
suffered from high level of reduced academic efficacy. While the students
attending the first grade reported higher level of reduced academic efficacy, the
students in the third grade reported higher level of emotional exhaustion.
Academic workload played an important role in the development of burnout. As
consequences of burnout, students with high levels of burnout intended to change
their current major and did not to plan to continue to postgraduate education.
Students with high level of burnout reported less level of academic satisfaction
and academic achievement. CONCLUSIONS: Creating awareness on the burnout of
dental students from the preclinical period may be useful for prevention and more
compatible dental education environment.
PMID- 26430364
TI - Expression of E-cadherin in normal oral mucosa, in oral precancerous lesions and
in oral carcinomas.
AB - OBJECTIVE: The aim of the present study was to assess the expression of E-cad in
oral precancerous lesions and conditions and oral carcinomas in comparison with
normal mucosa. MATERIALS AND METHODS: Total of 50 samples were selected for the
study and were categorized into five groups and 10 samples in each group as Group
I-oral leukoplakia (OL), Group II-oral lichen planus (OLP), Group III-oral
submucous fibrosis (OSMF), Group IV-oral squamous cell carcinoma (OSCC) and Group
V-normal oral mucosa (NOM) as control group. All the samples were assessed for
the expression of E-cad by immunohistochemical study. RESULTS: Upon assessing the
expression of E-cad in OL, OSMF, OLP and OSCC, as majority of the samples with
OSCC (90%), OL (80%), OLP (70%) and OSMF (60%) showed mild to moderate expression
of E-cad staining, which was suggestive of reduction in dysplastic cells on
comparison to NOM cells. This difference in expression and variation of E-cad
upon comparison with normal mucosa was statistically significant (P < 0.001).
CONCLUSION: There is significant (P < 0.001) variation of expression of E-cad
with the histopathological dysplasia of the oral precancerous lesions and
conditions, and the tumor differentiation of the oral cancers. However, there was
no correlation of the degree of loss of expression of E-cad with the degree of
dysplasia or the tumor differentiation of oral cancers. We conclude with our
study that, there is a variation in the expression of E-cad but its value as a
prognostic marker is questionable.
PMID- 26430365
TI - Impact of different malocclusion types on the vertical mandibular asymmetry in
young adult sample.
AB - OBJECTIVE: The aim of this study was to investigate the vertical mandibular
asymmetry in a group of adult patients with different types of malocclusions,
based on Angle's dental classification. MATERIALS AND METHODS: A sample of 102
patients (age range 19-28) who went for routine orthodontic treatment in the
institution were divided into four groups: Class I, 26 patients; Class II/1, 30
patients; Class III, 23 patients; and control group (CG) with normal occlusion,
23 patients. Condylar asymmetry index (CAI), ramal asymmetry index (RAI),
condylar-plus-ramal asymmetry index values were measured for all patients on
panoramic radiographs. Data were analyzed using Kruskal-Wallis and Mann-Whitney U
test at the 95% confidence level (P < 0.05). RESULTS: The results of the analysis
showed that different occlusal types significantly affected the vertical symmetry
of the mandible at the condylar level. Class I and Class II/1 malocclusion groups
showed a significant difference in CAI values relative to the CG (P < 0.05, P <
0.001). No statistically significant difference was found between the CG and
Class III malocclusion group (P > 0.05). Comparisons between Class II/1 and Class
I malocclusions revealed a significant difference in CAI values (P < 0.01).
CONCLUSIONS: Both Class II/1 and Class I malocclusions patients had significantly
higher CAI values compared to CG and Class III group. CAI value was significantly
higher in Class II/1 malocclusion compared to Class I malocclusion. Both these
malocclusions could act as a predisposing factor for having asymmetric condyles
if left untreated.
PMID- 26430366
TI - Effect of spreader size on microleakage of roots filled with cold lateral
compaction technique.
AB - OBJECTIVES: To evaluate the effect of spreader size on apical leakage of
maxillary incisor teeth. MATERIALS AND METHODS: A total of 75 permanent human
teeth with no carious and no fracture or crack were used for this study. After
removing the crown from the cementoenamel junction and the standardization of the
root lengths, the specimens were randomly divided into five groups: Group 1 -
Roots were not instrumented. Group 2 - Root canals were enlarged using the step
back technique to a #40 file and filled using cold lateral compaction (CLC) of
gutta-percha (GP). Group 3 - During the filling procedure, the first spreader
used was size 40. Group 4 - The first spreader used was size 35. Group 5 - The
initial spreader used was size 25. The amount of leakage through the filled root
canals was evaluated by computerized fluid filtration model. Statistical analyzes
were done using Kruskal-Wallis test and Mann-Whitney test (P < 0.05). RESULTS:
There were statistically significant differences among the groups (P < 0.05).
While the uninstrumented group (Group 1) had no leakage, instrumented but not
filled roots (Group 2) demonstrated the highest leakage values. There were no
differences between Group 3 and 4. Group 5 showed significantly less leakage than
Group 3 and 4. CONCLUSION: Spreader size used during CLC of GP appeared to be a
significant factor on apical leakage of roots. Using smaller size spreader during
CLC may provide relatively less leakage.
PMID- 26430367
TI - The influence of removable partial dentures on the periodontal health of abutment
and non-abutment teeth.
AB - OBJECTIVE: The aim of this study was to evaluate the influence of removable
partial dentures (RPD) on the periodontal health of abutment and non-abutment
teeth. MATERIALS AND METHODS: A total 107 patients with RPD participated in this
study. It was examined 138 RPD, they were 87 with clasp-retained and 51 were RPD
with attachments. The following periodontal parameters were evaluated for
abutment and non-abutment teeth, plaque index (PLI), calculus index (CI),
bleeding on probing (BOP), probing depth (PD) (mm) and tooth mobility (TM) index.
These clinical measurements were taken immediately before insertion the RPD, then
one and 3 months after insertion. The level of significance was set at (P <
0.05). RESULTS: The mean scores for PLI, CI, BOP, PD, and TM index, of the
abutment teeth and non-abutment teeth were no statistically significant at the
time of insertion of RPD. After 1-month, PLI was statistically significant (0.57
+/- 0.55 for abutment and 0.30 +/- 0.46 for non-abutment teeth). After 3 months,
there were significant differences between abutment and non-abutment teeth with
regard to the BOP (1.53 +/- 0.50 and 1.76 +/- 0.43 respectively), PD (0.28 +/-
0.45 and 0.12 +/- 0.33 respectively) and PLI (1.20 +/- 0.46 and 0.75 +/- 0.64
respectively). No significant mean difference in TM and CI was found between the
abutment and non-abutment teeth (P > 0.05). CONCLUSIONS: With carefully planned
prosthetic treatment and adequate maintenance of the oral and denture hygiene, we
can prevent the periodontal diseases.
PMID- 26430368
TI - Single nucleotide polymorphism at -1087 locus of interleukin-10 gene promoter is
associated with severe chronic periodontitis in nonsmoking patients.
AB - OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the promoter region of
interleukin (IL)-10 gene, which codes for the anti-inflammatory cytokine IL-10,
have been associated with its level of production in chronic periodontitis. The
prevalence of promoter SNP genotypes is known in other populations with chronic
periodontitis, while its association in the Indian population is not known.
Hence, the present study was designed to investigate the prevalence of IL-10
promoter polymorphism in a racially defined group of Indians with severe chronic
periodontitis as the Indian population is known to be genetically diverse.
MATERIALS AND METHODS: Genomic deoxyribonucleic acid was extracted from 46
nonsmoking patients with severe chronic periodontitis and 45 subjects with
healthy periodontium. A SNP locus at -1087 of IL-10 was chosen, as this locus has
been frequently associated with chronic periodontitis in other population.
Genotyping was carried out using allele-specific polymerase chain reaction (AS
PCR), and the frequencies of genotype were analyzed between the groups. RESULTS:
The distribution of genotype and allele frequencies showed significant
differences between the study groups. The prevalence of genotype AA alleles at
1087 locus of IL-10 was significantly higher in severe chronic periodontitis
patients compared to the healthy controls (P = 0.05). CONCLUSION: The study has
identified a positive association between the occurrence of AA allele at -1087
locus of IL-10 gene and severe chronic periodontitis in nonsmoking patients.
PMID- 26430369
TI - Establishment of a new relationship between posed smile width and lower facial
height: A cross-sectional study.
AB - OBJECTIVE: The present study is intended to add a new parameter that would be
useful in orthodontic clinical evaluation, treatment planning, and determination
of vertical dimension (at occlusion). MATERIALS AND METHODS: Standardized
videographic recording of 79 subjects during posed smile was captured. Each video
was then cut into 30 photos using the free studio software. The widest commissure
to-commissure posed smile frame (posed smile width [SW]) was selected as one of
10 or more frames showing an identical smile. Lower third of the face is measured
from subnasale to soft tissue menton using a digital vernier caliper. Two values
were then compared. Ratio between lower facial height and posed SW was
calculated. RESULTS: The co-relation between smiling width and lower facial
height was found to be statistically significant (P < 0.01). The ratio of lower
facial height and smiling width was calculated as 1.0016 with a standard
deviation (SD) = 0.04 in males and 1.0301 with an SD = 0.07 in females. The
difference between the mean lower facial height in males and females was
statistically significant with a t = 10.231 and P = 0.000. The difference between
the mean smiling width in males and females was also statistically significant
with a t = 5.653 and P = 0.000. CONCLUSION: In class I subjects with pleasing
appearance, normal facial proportions, normal overjet and overbite, and average
Frankfort mandibular angle, the lower facial height (subnasale to soft tissue
menton) is equal to posed SW.
PMID- 26430370
TI - The relationship between occlusal support and maxillary development: An animal
study.
AB - OBJECTIVE: To test the hypothesis that maxillary development may be affected by
occlusal support. MATERIALS AND METHODS: The sample was composed by Wistar rats
(5 weeks old) divided into three groups: Control (n = 10), extraction of
mandibular molar teeth - left side (n = 10), extraction mandibular molar teeth -
left and right sides (n = 10). The rats were sacrificed 8 weeks postextraction.
Cone beam computed tomography scan images were taken for posterior measurement of
maxillary length and width. Data were analyzed by one-way analysis of variance
(Tukey test as post-hoc test). RESULTS: Maxillary length was significantly
shorter (P < 0.005) in both groups after tooth extraction. No difference was
observed regarding maxillary width and body weight. CONCLUSION: Reduced occlusal
support may impair the development of the maxilla in rats.
PMID- 26430371
TI - Periodontal health status in patients treated with the Invisalign((r)) system and
fixed orthodontic appliances: A 3 months clinical and microbiological evaluation.
AB - OBJECTIVE: The aim of this prospective study was to compare the periodontal
health and the microbiological changes via real-time polymerase chain reaction
(PCR) in patients treated with fixed orthodontic appliances and Invisalign((r))
system (Align Technology, Santa Clara, California). MATERIALS AND METHODS:
Seventy-seven patients were enrolled in this study and divided into three groups
(Invisalign((r)) group, fixed orthodontic appliances group and control group).
Plaque index, probing depth, bleeding on probing were assessed. Total biofilm
mass and periodontal pathogens were analyzed and detected via real-time PCR. All
these data were analyzed at the T0 (beginning of the treatment) T1 (1-month) and
T2 (3 months); and statistically compared using the Mann-Whitney test for
independent groups. RESULTS: After 1-month and after 3 months of treatment there
was only one sample with periodontopathic anaerobes found in patient treated
using fixed orthodontic appliances. The Invisalign((r)) group showed better
results in terms of periodontal health and total biofilm mass compared to the
fixed orthodontic appliance group. A statistical significant difference (P <
0.05) at the T2 in the total biofilm mass was found between the two groups.
CONCLUSION: Patients undergoing orthodontic treatment with the Invisalign((r))
System show a superior periodontal health in the short-term when compared to
patients in treatment with fixed orthodontic appliances. Invisalign((r)) should
be considered as a first treatment option in patients with risk of developing
periodontal disease.
PMID- 26430372
TI - Antimicrobial activity of a temporary sealant used in endodontic treatment: An in
vitro study.
AB - OBJECTIVE: The present study is aimed to evaluate the antimicrobial action of
Coltosol((r)) in direct contact with human saliva. MATERIALS AND METHODS: Twelve
different individuals were selected. Saliva samples were evaluated at four
different time periods: Baseline 1 (T1-initial control), T2 (2 h), T4 (24 h after
contact with a standardized sample of a coronary sealer) and baseline 2 (T3-final
control). Seeded plates were incubated at 37 degrees C in a bacterial incubator
for a period of 48-72 h. After the incubation period, the colony forming units
were counted, and the results compared. RESULTS: Differences were statistically
significant. There was an inhibition of bacterial growth after the first 2 h of
contact and an increase in the number of bacteria after 24 h of direct contact
between the material and the saliva. Coltosol((r)) presented bacterial growth
inhibition in direct contact with saliva. This inhibitory effect tended to
decrease over time, as shown by the two periods when the material was in contact
with different samples of saliva. CONCLUSIONS: The antimicrobial activity of the
material is an important feature; however, other physical and chemical properties
of the coronary temporary sealer should be considered.
PMID- 26430373
TI - Evaluation of non-surgical therapy on glutathione levels in chronic
periodontitis.
AB - OBJECTIVE: To compare the levels of glutathione (GSH), both oxidized and reduced
forms in patients with and without chronic periodontitis in gingival crevicular
fluid (GCF). MATERIALS AND METHODS: Twenty GCF samples from maxillary quadrants
were collected using capillary micropipettes from the chronic periodontitis
patients (test group) at baseline before treatment, at 1-month, 3 months, and 6
months after scaling and root planing and samples from 20 patients without
chronic periodontitis (control group) from maxillary quadrants were also
collected. GSH, oxidized glutathione (GSSG) levels and GSH: GSSG ratios were
determined using the spectrophotometric method. STATISTICAL ANALYSIS: Results
were concluded for the test over control groups using paired Student's t-test.
RESULTS: Lower concentrations of GSH (P < 0.001) and GSSG (P < 0.001) were
detected in GCF in patients with chronic periodontitis (test group) than patients
without chronic periodontitis (control group) at baseline. Treatment had a
significant effect in improving the GSH and reducing GSSG levels postscaling and
root planing at 1-month and 3 months but not significant effect at 6 months.
Scaling and root planing increased the GSH: GSSG ratio (P < 0.001) in the test
group as compared to the control group (P < 0.001). CONCLUSIONS: The
concentrations of GSH within GCF are reduced in chronic periodontitis patients.
Scaling and root planing (nonsurgical therapy) restores GSH concentration in GCF
post 1-month and 3 months along with redox balance (GSH: GSSG ratio), but at 6
months the balance is not maintained. Adjunctive use of micronutritional
supplements to boost antioxidant concentration in tissues by preserving GSH or by
elevating its level at the inflamed sites is recommended, as nonsurgical
periodontal therapy alone is not able to maintain redox balance for longer
duration.
PMID- 26430374
TI - Pulp tissue dissolution capacity of QMix 2in1 irrigation solution.
AB - OBJECTIVE: The aim of this study was to evaluate the tissue dissolution efficacy
of four root canal irrigation solutions (sodium hypochlorite [NaOCl],
chlorhexidine gluconate [CHX], Octenidine [OCT], and QMix 2in1) on bovine pulp
tissue. MATERIALS AND METHODS: Fifty bovine pulp tissue samples, each weighing
6.55 mg, were prepared and randomly divided into four experimental groups and one
control group (n = 10) according to the dissolution irrigants used: (1) 5.25%
NaOCl group; (2) 2% CHX group; (3) OCT group; (4) QMix 2in1 group; and (5)
control group (saline solution). These samples were then placed into special
bovine dentin reservoir models and immersed for 1 h with each test solution (0.1
mL of each) at room temperature. The pulp samples were then blotted dry and
weighed again. The percentage of weight loss was calculated. Statistically
analyzed with one-way analysis of variance and post-hoc Tukey tests (P = 0.05).
RESULTS: Saline solution did not dissolve the bovine pulp tissue. All groups,
except OCT, dissolved pulp samples more effectively than the control group (P <
0.05). The highest tissue dissolution was observed in 5.25% NaOCl group (P <
0.05). No statistically significant difference was found between the tissue
dissolving effect between QMix 2in1 and those of 2% CHX. CONCLUSIONS: Within the
limitations of this in vitro study, NaOCl exhibited the best tissue-dissolving
effect out of all solutions tested. CHX and QMix 2in1 were able to dissolve pulp
tissue but less than NaOCl. OCT and saline solutions could not exhibit
significantly tissue-dissolving effectiveness. This study shown that QMix 2in1
has little capacity to dissolve pulp tissue therefore used alone is not
sufficient for this purpose.
PMID- 26430375
TI - Stress distribution of endodontically treated teeth with titanium alloy post and
carbon fiber post with different alveolar bone height: A three-dimensional finite
element analysis.
AB - OBJECTIVE: A three-dimensional (3D) finite element analysis (FEA) on the stress
distribution of endodontically treated teeth with titanium alloy post and carbon
fiber post with different alveolar bone height. MATERIALS AND METHODS: The 3D
model was fabricated using software to represent an endodontically treated
mandibular second premolar with post and restored with a full ceramic crown
restoration, which was then analyzed using FEA using FEA ANSYS Workbench V13.0
(ANSYS Inc., Canonsburg, Pennsylvania, U.S.A) software. RESULTS: The FEA showed
the maximum stresses of 137.43 Mpa in dentin with alveolar bone height of 4 mm
when the titanium post was used, 138.48 Mpa when carbon fiber post was used as
compared to 105.91 Mpa in the model with alveolar bone height of 2 mm from the
cement enamel junction (CEJ) when the titanium post was used and 107.37 Mpa when
the carbon fiber post was used. CONCLUSIONS: Stress was observed more in alveolar
bone height level of 4 mm from CEJ than 2 mm from CEJ. Stresses in the dentin
were almost similar when the carbon fiber post was compared to titanium post.
However, stresses in the post and the cement were much higher when titanium post
was used as compared to carbon fiber post.
PMID- 26430376
TI - A different wax sculpture technique for implant-retained auricular prosthesis.
AB - Replacement of missing ears is a challenging task in which extensive array of
materials and techniques have been employed. This article describes a different
and simplified procedure for fabricating auricular prostheses very similar to the
intact left ear of the patient. A 65-year-old male patient was referred to the
Department of Prosthodontics with the loss of the right ear. In this case, the
impression was made using hydrocolloid material (alginate) from the both defected
and the opposite side. After hardening of the stone casts, a custom-made
transparent splint plate was designed for the left auricular side. The splint was
reversed and a cast model of the right auricular side was obtained as pouring the
dental stone into transparent orthodontic splint. After getting the impression
from cast model, conventional wax pattern and try on process was done. Finally,
silicone elastomer was polymerized and the retention of the prosthesis acquired
with the magnetic attachments. The technique described is economical,
conventional, and time-saving. Furthermore, the prosthesis imitates the patient's
intact auricular tissue.
PMID- 26430377
TI - Unusual intraosseous capillary hemangioma of the mandible.
AB - Intraosseous hemangioma is a benign vascular neoplasm, which is mostly seen in
vertebrae, maxillofacial bones, and long bones. Intraosseous hemangioma is rarely
seen on jaw bones compared to other skeletal bones and usually occurs in the
cavernous form. Capillary intraosseous hemangioma of jaws is an uncommon form of
intraosseous hemangioma and has not been thoroughly described so far. In this
study, a case of capillary intraosseous hemangioma of the mandible was presented
with relevant literature review.
PMID- 26430378
TI - Implant-supported hybrid prosthesis: Conventional treatment method for borderline
cases.
AB - An implant-supported hybrid prosthesis is an acrylic resin complete fixed dental
prosthesis and supported by implants might be a solution in extreme cases that
the need of the restoration for esthetics, function, lip support, and speech.
This clinical report aims to present the esthetic and functional prosthetic
rehabilitation of three borderline cases with implant-supported hybrid
prostheses. Patient 1 (62-year-old man) and Patient 2 (61-year-old man) presented
a chief complaint of a compromised esthetic. After clinical evaluations, in
Patient 1, 8 implants in the maxilla and 7 implants in mandibula were observed.
Patient 2 had 7 implants in the maxilla and 7 implants in mandibula, which were
previously placed. The intra-arch dimension of both patients was excessive and an
insufficient peri-oral soft tissue support was observed. Patient 3 was a 61-year
old man had 2 implants with a history of previously implanted graft infection and
implant loss on his maxillary posterior jaw. An excessive intra-arch dimension
was observed in clinical examination. In addition, massive bone defect and
insufficient soft tissue support were examined. In all patients, implant
supported hybrid prostheses were successfully performed. The clinical and
radiologic findings were satisfactory. After 3 years of follow-up, no functional,
phonetic, or esthetic problems with the restorations were noted. These case
reports suggest that implant-supported hybrid prostheses can be a reliable
alternative treatment procedure when a porcelain-fused metal fixed restoration
does not satisfy a patient's requirements for esthetics, phonetics, oral hygiene,
and oral comfort.
PMID- 26430379
TI - Erythematous candidiasis leading to systemic manifestations of human
immunodeficiency virus co-infection with secondary syphilis: A diagnostic and
therapeutic dilemma.
AB - The intensification of human immunodeficiency virus (HIV) and rising frequency of
immunocompromised individuals have resulted in a resurgence of opportunistic
infections. The most common opportunistic oral fungal infection in HIV-positive
individuals is oral candidiasis. The classical presentation is as white scrapable
form called as thrush, which is easily diagnosed and treated. The clinician is
presented with a diagnostic and management dilemma when these lesions appear in
new facades such as erythematous candidiasis, the latter's prevalence with HIV
and AIDS being well established. In this case report, we present a case of
Erythematous Candidiasis, which was associated with type 1 HIV co-infected with
syphilis. We highlight the diagnostic importance of a naive looking manifestation
of the tongue which was followed by a series of challenging presentations of
secondary syphilis. Since the patient had a negative Veneral Disease Research
Laboratory and left us with a management dilemma, the article also features the
importance of prozone phenomenon (seen in 2% cases of secondary syphilis), and
it's higher association with HIV co-infected individuals. With confusing clinical
oral manifestations associated with these diseases, the dentist might be the
first person to encounter such lesions, who should be able to recognize
erythematous candidiasis and correlate them with the underlying pathology.
PMID- 26430380
TI - Verrucous carcinoma and squamous cell papilloma of the oral cavity: Report of two
cases and review of literature.
AB - Verrucous carcinoma (VC) of oral cavity is a rare variant of well-differentiated
squamous cell carcinoma and squamous papilloma is a benign proliferation of the
stratified squamous epithelium, which results in a papillary or verrucous
exophytic mass. There is a certain clinical similarity between squamous cell
papilloma and VC. We presented a report of two cases which are VC and squamous
cell papilloma that are showed the same clinical appearance but different
pathological appearance, with a review of the literature.
PMID- 26430381
TI - Conservation planning in agricultural landscapes: hotspots of conflict between
agriculture and nature.
AB - AIM: Conservation conflict takes place where food production imposes a cost on
wildlife conservation and vice versa. Where does conservation impose the maximum
cost on production, by opposing the intensification and expansion of farmland?
Where does conservation confer the maximum benefit on wildlife, by buffering and
connecting protected areas with a habitable and permeable matrix of crop and non
crop habitat? Our aim was to map the costs and benefits of conservation versus
production and thus to propose a conceptual framework for systematic conservation
planning in agricultural landscapes. LOCATION: World-wide. METHODS: To quantify
these costs and benefits, we used a geographic information system to sample the
cropland of the world and map the proportion of non-crop habitat surrounding the
cropland, the number of threatened vertebrates with potential to live in or move
through the matrix and the yield gap of the cropland. We defined the potential
for different types of conservation conflict in terms of interactions between
habitat and yield (potential for expansion, intensification, both or neither). We
used spatial scan statistics to find 'hotspots' of conservation conflict.
RESULTS: All of the 'hottest' hotspots of conservation conflict were in sub
Saharan Africa, which could have impacts on sustainable intensification in this
region. MAIN CONCLUSIONS: Systematic conservation planning could and should be
used to identify hotspots of conservation conflict in agricultural landscapes, at
multiple scales. The debate between 'land sharing' (extensive agriculture that is
wildlife friendly) and 'land sparing' (intensive agriculture that is less
wildlife friendly but also less extensive) could be resolved if sharing and
sparing were used as different types of tool for resolving different types of
conservation conflict (buffering and connecting protected areas by maintaining
matrix quality, in different types of matrix). Therefore, both sharing and
sparing should be prioritized in hotspots of conflict, in the context of
countryside biogeography.
PMID- 26430382
TI - Exposure to English Before and After Entry into Head Start: Bilingual Children's
Receptive Language Growth in Spanish and English.
AB - This investigation examined the Spanish and English receptive vocabulary and
language comprehension abilities of bilingual preschoolers who attended Head
Start over a two-year period. It was hypothesised that bilingual children's
development would follow linear trajectories and that the development of children
who were only exposed to Spanish in the home prior to school entry would differ
from children with exposure to Spanish and English from birth. Results revealed
that the two groups' language abilities in Spanish and English differed at the
beginning of the study as measured by raw and standard scores and that these
differences were maintained over the two years. The exceptions to this were found
in the children's vocabulary abilities, with the difference between the two
groups' English standard scores narrowing over time and the difference between
their Spanish standard scores increasing during the two-year period. Similar to
research on monolingual and bilingual children with low socioeconomic status
(SES), children's development in both languages essentially followed linear
trajectories. Children's raw scores on the English receptive vocabulary test
accelerated, similar to research findings on monolingual children of middle SES.
Also, children's standard scores on the Spanish language comprehension measure
decelerated after an initial period of linear growth. Future directions for
research are discussed.
PMID- 26430383
TI - Extinction of an introduced warm-climate alien species, Xenopus laevis, by
extreme weather events.
AB - Invasive, non-native species represent a major threat to biodiversity worldwide.
The African amphibian Xenopus laevis is widely regarded as an invasive species
and a threat to local faunas. Populations originating at the Western Cape, South
Africa, have been introduced on four continents, mostly in areas with a similar
Mediterranean climate. Some introduced populations are also established in cooler
environments where persistence for many decades suggests a capacity for long-term
adaptation. In these cases, recent climate warming might enhance invasion
ability, favouring range expansion, population growth and negative effects on
native faunas. In the cool temperate UK, populations have been established for
about 50 years in Wales and for an unknown period, probably >20 years, in England
(Lincolnshire). Our field studies over 30 and 10 years, respectively, show that
in favourable conditions there may be good recruitment, fast individual growth
rates and large body size; maximum longevity exceeds 23 years. Nevertheless,
areas of distribution remained limited, with numbers <500 in each population. In
2010, only a single individual was captured at each locality and further
searching failed to record any others in repeated sampling up to 2014. We
conclude that both populations are now extinct. The winters of 2009-2010 and 2010
2011 experienced extreme cold and drought (December 2010 was the coldest in 120
years and the third driest in 100 years). The extinction of X. laevis in these
areas indicates that even relatively long-established alien species remain
vulnerable to rare extreme weather conditions.
PMID- 26430384
TI - Dark-matter production through loop-induced processes at the LHC: the s-channel
mediator case.
AB - We show how studies relevant for mono-X searches at the LHC in simplified models
featuring a dark-matter candidate and an s-channel mediator can be performed
within the MadGraph5_aMC@NLO framework. We focus on gluon-initiated loop-induced
processes, mostly relevant to the case where the mediator couples preferentially
to third generation quarks and in particular to the top quark. Our implementation
allows us to study signatures at hadron colliders involving missing transverse
energy plus jets or plus neutral bosons ([Formula: see text]), possibly including
the effects of extra radiation by multi-parton merging and matching to the parton
shower.
PMID- 26430385
TI - Global patterns of freshwater species diversity, threat and endemism.
AB - AIM: Global-scale studies are required to identify broad-scale patterns in the
distributions of species, to evaluate the processes that determine diversity and
to determine how similar or different these patterns and processes are among
different groups of freshwater species. Broad-scale patterns of spatial variation
in species distribution are central to many fundamental questions in macroecology
and conservation biology. We aimed to evaluate how congruent three commonly used
metrics of diversity were among taxa for six groups of freshwater species.
LOCATION: Global. METHODS: We compiled geographical range data on 7083 freshwater
species of mammals, amphibians, reptiles, fishes, crabs and crayfish to evaluate
how species richness, richness of threatened species and endemism are distributed
across freshwater ecosystems. We evaluated how congruent these measures of
diversity were among taxa at a global level for a grid cell size of just under 1
degrees . RESULTS: We showed that although the risk of extinction faced by
freshwater decapods is quite similar to that of freshwater vertebrates, there is
a distinct lack of spatial congruence in geographical range between different
taxonomic groups at this spatial scale, and a lack of congruence among three
commonly used metrics of biodiversity. The risk of extinction for freshwater
species was consistently higher than for their terrestrial counterparts. MAIN
CONCLUSIONS: We demonstrate that broad-scale patterns of species richness,
threatened-species richness and endemism lack congruence among the six freshwater
taxonomic groups examined. Invertebrate species are seldom taken into account in
conservation planning. Our study suggests that both the metric of biodiversity
and the identity of the taxa on which conservation decisions are based require
careful consideration. As geographical range information becomes available for
further sets of species, further testing will be warranted into the extent to
which geographical variation in the richness of these six freshwater groups
reflects broader patterns of biodiversity in fresh water.
PMID- 26430386
TI - Analysis of stable states in global savannas: is the CART pulling the horse?
AB - Multiple stable states, bifurcations and thresholds are fashionable concepts in
the ecological literature, a recognition that complex ecosystems may at times
exhibit the interesting dynamic behaviours predicted by relatively simple
biomathematical models. Recently, several papers in Global Ecology and
Biogeography, Proceedings of the National Academy of Sciences USA, Science and
elsewhere have attempted to quantify the prevalence of alternate stable states in
the savannas of Africa, Australia and South America, and the tundra-taiga
grassland transitions of the circum-boreal region using satellite-derived woody
canopy cover. While we agree with the logic that basins of attraction can be
inferred from the relative frequencies of ecosystem states observed in space and
time, we caution that the statistical methodologies underlying the satellite
product used in these studies may confound our ability to infer the presence of
multiple stable states. We demonstrate this point using a uniformly distributed
'pseudo-tree cover' database for Africa that we use to retrace the steps involved
in creation of the satellite tree-cover product and subsequent analysis. We show
how classification and regression tree (CART)-based products may impose
discontinuities in satellite tree-cover estimates even when such discontinuities
are not present in reality. As regional and global remote sensing and geospatial
data become more easily accessible for ecological studies, we recommend careful
consideration of how error distributions in remote sensing products may interact
with the data needs and theoretical expectations of the ecological process under
study.
PMID- 26430387
TI - Markedly divergent estimates of Amazon forest carbon density from ground plots
and satellites.
AB - AIM: The accurate mapping of forest carbon stocks is essential for understanding
the global carbon cycle, for assessing emissions from deforestation, and for
rational land-use planning. Remote sensing (RS) is currently the key tool for
this purpose, but RS does not estimate vegetation biomass directly, and thus may
miss significant spatial variations in forest structure. We test the stated
accuracy of pantropical carbon maps using a large independent field dataset.
LOCATION: Tropical forests of the Amazon basin. The permanent archive of the
field plot data can be accessed at:
http://dx.doi.org/10.5521/FORESTPLOTS.NET/2014_1. METHODS: Two recent pantropical
RS maps of vegetation carbon are compared to a unique ground-plot dataset,
involving tree measurements in 413 large inventory plots located in nine
countries. The RS maps were compared directly to field plots, and kriging of the
field data was used to allow area-based comparisons. RESULTS: The two RS carbon
maps fail to capture the main gradient in Amazon forest carbon detected using 413
ground plots, from the densely wooded tall forests of the north-east, to the
light-wooded, shorter forests of the south-west. The differences between plots
and RS maps far exceed the uncertainties given in these studies, with whole
regions over- or under-estimated by > 25%, whereas regional uncertainties for the
maps were reported to be < 5%. MAIN CONCLUSIONS: Pantropical biomass maps are
widely used by governments and by projects aiming to reduce deforestation using
carbon offsets, but may have significant regional biases. Carbon-mapping
techniques must be revised to account for the known ecological variation in tree
wood density and allometry to create maps suitable for carbon accounting. The use
of single relationships between tree canopy height and above-ground biomass
inevitably yields large, spatially correlated errors. This presents a significant
challenge to both the forest conservation and remote sensing communities, because
neither wood density nor species assemblages can be reliably mapped from space.
PMID- 26430388
TI - Evolutionary impact assessment: accounting for evolutionary consequences of
fishing in an ecosystem approach to fisheries management.
AB - Managing fisheries resources to maintain healthy ecosystems is one of the main
goals of the ecosystem approach to fisheries (EAF). While a number of
international treaties call for the implementation of EAF, there are still gaps
in the underlying methodology. One aspect that has received substantial
scientific attention recently is fisheries-induced evolution (FIE). Increasing
evidence indicates that intensive fishing has the potential to exert strong
directional selection on life-history traits, behaviour, physiology, and
morphology of exploited fish. Of particular concern is that reversing
evolutionary responses to fishing can be much more difficult than reversing
demographic or phenotypically plastic responses. Furthermore, like climate
change, multiple agents cause FIE, with effects accumulating over time.
Consequently, FIE may alter the utility derived from fish stocks, which in turn
can modify the monetary value living aquatic resources provide to society.
Quantifying and predicting the evolutionary effects of fishing is therefore
important for both ecological and economic reasons. An important reason this is
not happening is the lack of an appropriate assessment framework. We therefore
describe the evolutionary impact assessment (EvoIA) as a structured approach for
assessing the evolutionary consequences of fishing and evaluating the predicted
evolutionary outcomes of alternative management options. EvoIA can contribute to
EAF by clarifying how evolution may alter stock properties and ecological
relations, support the precautionary approach to fisheries management by
addressing a previously overlooked source of uncertainty and risk, and thus
contribute to sustainable fisheries.
PMID- 26430390
TI - The Interdependence of Adult Relationship Quality and Parenting Behaviours among
African American and European Couples in Rural, Low-Income Communities.
AB - The present study extends the spillover and crossover hypotheses to more
carefully model the potential interdependence between parent-parent interaction
quality and parent-child interaction quality in family systems. Using propensity
score matching, the present study attempted to isolate family processes that are
unique across African American and European American couples that are independent
of other socio-demographic factors to further clarify how interparental
relationships may be related to parenting in a rural, low-income sample. The
Actor-Partner Interdependence Model (APIM), a statistical analysis technique that
accounts for the interdependence of relationship data, was used with a sample of
married and non-married cohabiting African American and European American couples
(n = 82 dyads) to evaluate whether mothers' and fathers' observed parenting
behaviours are related to their behaviours and their partner's behaviours
observed in a couple problem-solving interaction. Findings revealed that
interparental withdrawal behaviour, but not conflict behaviour, was associated
with less optimal parenting for fathers but not mothers, and specifically so for
African American fathers. Our findings support the notion of interdependence
across subsystems within the family and suggest that African American fathers may
be specifically responsive to variations in interparental relationship quality.
PMID- 26430391
TI - Maternal Behavior Modifications during Pretense and Their Long-Term Effects on
Toddlers' Understanding of Pretense.
AB - Recent studies indicate the need to investigate the sources of toddlers'
understanding of another person's pretense. The present study is a cultural and
longitudinal extension of the work of Lillard and Witherington (2004), who
claimed that mothers modify their behaviors during pretense and that the some of
these behavior modifications help their toddlers understand maternal pretense.
Experiment 1 investigated whether mothers would change their behaviors during
pretense with a sample of 31 Japanese mother-infant pairs. Experiment 2, with a
subsample of 20 mother-child pairs who had participated in Experiment 1, examined
whether the maternal behavior modifications at 18 months predicted their
toddlers' understanding of pretense at 24 months. The results of Experiment 1
indicated that Japanese mothers smiled more frequently, gazed at their toddlers
longer, used sound effects more frequently, and engaged in more frequent snack
related actions in a "pretense condition" than in a "real condition." In
addition, some of these behaviors were significantly related to their toddlers'
apparent understanding of pretense. Experiment 2 showed that both the frequency
of maternal smiles and the number of sound effects in the pretense condition at
18 months predicted toddlers' understanding of the pretense enacted by a strange
adult at 24 months. This research indicates the impact of maternal behavior
modifications during pretense on the development of symbolic thought in the 2nd
year of life.
PMID- 26430389
TI - Biomarkers and severe asthma: a critical appraisal.
AB - Severe asthma (SA) is a clinically and etiologically heterogeneous respiratory
disease which affects among 5-10 % of asthmatic patients. Despite high-dose
therapy, a large patients percentage is not fully controlled and has a poor
quality of life. In this review, we describe the biomarkers actually known in
scientific literature and used in clinical practice for SA assessment and
management: neutrophils, eosinophils, periostin, fractional exhaled nitric oxide,
exhaled breath condensate and galectins. Moreover, we give an overview on
clinical and biological features characterizing severe asthma, paying special
attention to the potential use of these ones as reliable markers. We finally
underline the need to define different biomarkers panels to select patients
affected by severe asthma for specific and personalized therapeutic approach.
PMID- 26430392
TI - Update in Urothelial Carcinoma: Novel Agents and Targeted Therapy.
AB - Urothelial carcinoma (UC) is a chemosensitive disease with high response rates to
platinum-based combination chemotherapy in locally advanced or advanced disease.
However, de novo or emergence of cisplatin-resistance limits the duration of
response, patients are frequently ineligible for cisplatin, and therapies tested
thus far have minimal activity as second-line therapy. The first wave of clinical
trials of novel agents and targeted therapy have modestly advanced the field and
laid the foundations for future studies. These trials include the deployment of
monoclonal antibodies and tyrosine kinase inhibitors that target mediators of
angiogenesis and growth receptors. Novel cytotoxic agents have also been tested
as single-agents in the second-line setting and together with the first-line
combination of gemcitabine with cisplatin. To date, these novel agents have yet
to demonstrate the ability to substantially improve the overall survival of
patients with bladder cancer. Comparative trials of chemotherapy with or without
a novel agent are ongoing and have the potential to improve upon current standard
therapy. Moreover, state-of-the-art technologies have been developed that will
likely identify the molecular alterations which drive both UC and platinum
resistance and in turn provide opportunities for drug development. The latter
includes an interrogation of microRNAs and the integrated study of genetic
mutations in extreme phenotypes of the disease. In essence, this ongoing work
paired with physician and patient commitments to clinical trial participation
will ultimately lead to advances in the care of patients with urothelial cancer.
PMID- 26430393
TI - Transmembrane helices in "classical" nuclear reproductive steroid receptors: a
perspective.
AB - Steroid receptors of the nuclear receptor superfamily are proposed to be either:
1) located in the cytosol and moved to the cell nucleus upon activation, 2)
tethered to the inside of the plasma membrane, or 3) retained in the nucleus
until free steroid hormone enters and activates specific receptors. Using
computational methods to analyze peptide receptor topology, we find that the
"classical" nuclear receptors for progesterone (PRB/PGR), androgen (ARB/AR) and
estrogen (ER1/ESR1) contain two transmembrane helices (TMH) within their ligand
binding domains (LBD).The MEMSAT-SVM algorithm indicates that ARB and ER2 (but
not PRB or ER1) contain a pore-lining (channel-forming) region which may merge
with other pore-lining regions to form a membrane channel. ER2 lacks a TMH, but
contains a single pore-lining region. The MemBrain algorithm predicts that PRB,
ARB and ER1 each contain one TMH plus a half TMH separated by 51 amino acids.ER2
contains two half helices. The TM-2 helices of ARB, ER1 and ER2 each contain 9-13
amino acid motifs reported to translocate the receptor to the plasma membrane, as
well as cysteine palmitoylation sites. PoreWalker analysis of X-ray
crystallographic data identifies a pore or channel within the LBDs of ARB and ER1
and predicts that 70 and 72 residues are pore-lining residues, respectively. The
data suggest that (except for ER2), cytosolic receptors become anchored to the
plasma membrane following synthesis. Half-helices and pore-lining regions in turn
form functional ion channels and/or facilitate passive steroid uptake into the
cell. In perspective, steroid-dependent insertion of "classical" receptors
containing pore-lining regions into the plasma membrane may regulate permeability
to ions such as Ca(2+), Na(+) or K(+), as well as facilitate steroid
translocation into the nucleus.
PMID- 26430394
TI - Continuous-flow Ferrohydrodynamic Sorting of Particles and Cells in Microfluidic
Devices.
AB - A new sorting scheme based on ferrofluid hydrodynamics (ferrohydrodynamics) was
used to separate mixtures of particles and live cells simultaneously. Two species
of cells, including Escherichia coli and Saccharomyces cerevisiae, as well as
fluorescent polystyrene microparticles were studied for their sorting throughput
and efficiency. Ferrofluids are stable magnetic nanoparticles suspensions. Under
external magnetic fields, magnetic buoyancy forces exerted on particles and cells
lead to size-dependent deflections from their laminar flow paths and result in
spatial separation. We report the design, modeling, fabrication and
characterization of the sorting device. This scheme is simple, low-cost and label
free compared to other existing techniques.
PMID- 26430396
TI - What ails the Pakistani medical institutions?
PMID- 26430395
TI - Exposure to 50 Hz electromagnetic field changes the efficiency of the scorpion
alpha toxin.
AB - BACKGROUND: Extremely low-frequency (50 Hz) electromagnetic field (ELF-EMF) is
produced by electric power transmission lines and electronic devices of everyday
use. Some phenomena are proposed as "first effects" of ELF-EMF: the discrete
changes in the membrane potential and the increase of the calcium channel
activity as well as the intracellular concentration of Ca(2+). Interaction of the
scorpion alpha toxin with the sodium channel depends on the orientation of the
charges and may be perturbed by changes in the membrane polarization. The toxin
induces overexcitability in the nervous system and an increase in the
neurotransmitters released with different consequences, mainly the paralysis of
muscles. We assumed that the exposure to ELF-EMF 0.7 mT will change the effects
of the insect selective scorpion alpha toxin (recombinant LqhalphaIT from Leiurus
quinquestriatus hebraeus) at the level of the cercal nerve function, the synaptic
transmission and on the level of entire insect organism. Taking into account the
compensatory mechanisms in organisms, we tested in addition ten times higher ELF
EMF on whole insects. METHODS: Experiments were performed in vivo on cockroaches
(Periplaneta americana) and in vitro - on isolated cockroach abdominal nerve cord
with cerci. In biotests, the effects of LqhalphaIT (10(-8) M) were estimated on
the basis of the insect ability to turn back from dorsal to ventral side. Three
groups were compared: the control one and the two exposed to ELF-EMF - 0.7 and 7
mT. Bioelectrical activity of the cercal nerve and of the connective nerve that
leaves the terminal abdominal ganglion was recorded using extracellular
electrodes. LqhalphaIT (5 * 10(-8) M) induced modifications of neuronal activity
that were observed in the control cockroach preparations and in the ones exposed
to ELF-EMF (0.7 mT). The exposure to ELF-EMF was carried out using coils with a
size appropriate to the examined objects. RESULTS: The exposure to ELF-EMF (0.7
mT) modified the effects of LqhalphaIT (5 * 10(-8) M) on activity of the cercal
nerve and of the connective nerve. We observed a decrease of the toxin effect on
the cercal nerve activity, but the toxic effect of LqhalphaIT on the connective
nerve was increased. Biotests showed that toxicity of LqhalphaIT (10(-8) M) on
cockroaches was reduced by the exposure to ELF-EMF (0.7 and 7 mT). CONCLUSIONS:
The exposure to 50 Hz ELF-EMF modified the mode of action of the anti-insect
scorpion alpha toxin LqhalphaIT at cellular level of the cockroach nervous system
and in biotests. Toxin appeared as a usefull tool in distinguishing between the
primary and the secondary effects of ELF-EMF.
PMID- 26430397
TI - Comparison of microcoils and polyvinyl alcohol particles in selective
microcatheter angioembolization of non variceal acute gastrointestinal
hemorrhage.
AB - OBJECTIVES: To compare the efficacy of polyvinyl alcohol (PVA) particles with
microcoils in angiembolisation of non variceal acute gastrointestinal
haemorrhage. METHODS: This is a retrospective cross-sectional study of patients
who underwent transcatheter angioembolization from January, 1995 to December,
2013 at Aga Khan University Hospital, Karachi. Patients were divided into two
groups on basis of use of either microcoils or PVA particles and compared in
terms of technical success, clinical success, re-bleeding and ischemic
complication rates. Chi (chi(2)) square and Fisher's exact tests were applied and
a P-value of less than 0.05 was considered statistically significant. RESULTS:
Fifty seven patients underwent angioembolization. Microcoil and PVA particles
embolization was performed in 63% (36/57) and 35% (20/57) cases respectively.
Technical success was achieved in all cases (100%). Clinical success rate was
higher in microcoils group (92%) than PVA particles group (75%) with
statistically significant P value (p=0.048). Ischemic complication was seen in
one case (3%) in the microcoil group, while no such complications were seen in
the PVA particles group. CONCLUSION: In angioembolization of non variceal acute
gastrointestinal haemorrhage microcoils are better than Polyvinyl alcohol
particles with higher clinical success and lower re-bleed rates.
PMID- 26430398
TI - Perceptions of clinical years' medical students and interns towards assessment
methods used in King Abdulaziz University, Jeddah.
AB - OBJECTIVES: The study was done to determine the perception of clinical years'
medical students and interns about assessment methods used in Faculty of
Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. METHODS: A cross
sectional study was conducted during the educational year 2012/2013. A multistage
stratified random sample method was used to select 600 senior medical students
(4(th)-6(th)) and interns. Perception of medical students and interns about
different assessment formats was inquired using 3 points Likert scale. RESULTS:
About two-fifths of participants agreed that assessment methods are
comprehensive, reflecting what they taught, and challenging them. MCQs were the
commonest (56.8%) preferred written assessment format. OSCE (74.1%) and OSPE
(70.6%) were seen as good tools for assessing clinical competencies. Students had
good perceptions towards peer assessment, log-book and open book exams. Males
preferred peer assessment method more than females, with a statistical
significant difference (chi(2) = 6.43, p< 0.05). CONCLUSION: Assessment plan
needs further improvements and should be designed prospectively along with
learning outcomes, as only about 40 % of participants agreed with assessment
items. The current development of the faculty Assessment Unit will provide much
help. This will lead to better preparation of medical students for their future
responsibility as tomorrow's doctors.
PMID- 26430399
TI - Can living donor liver transplantation offer similar outcomes to deceased donor
liver transplantation using expanded selection criteria for hepatocellular
carcinoma?
AB - OBJECTIVE: To compare the outcomes of living donor liver transplantation (LDLT)
versus deceased donor liver transplantation (DDLT) for patients with
hepatocellular carcinoma (HCC) in different selection criteria. METHODS: Data of
patients with HCC who underwent liver transplantation between 2005 and 2013 at
our center were reviewed. Clinical data of LDLT recipients and DDLT recipients
were compared. The postoperative recurrence-free survival (RFS) rate and overall
survival (OS) rate after LDLT versus DDLT were compared in the Milan recipients,
the University of California, San Francisco (UCSF) recipients, the up-to-seven
recipients, the Hangzhou recipients and the Chengdu recipients. RESULTS: Data of
255 patients were retrospectively reviewed in this study. Seventeen DDLT
recipient and 9 LDLT recipients died during the perioperative period. Among the
remaining 229 recipients (NLDLT=66, NDDLT=163), 96 patients met the Milan
criteria, 123 recipients met the UCSF criteria, 135 patients met the up-to-seven
criteria, 216 patients met the Hangzhou criteria, and 229 recipients met the
Chengdu criteria. The overall RFS and OS rates of the Milan recipients, the UCSF
recipients, the up-to-seven recipients, the Hangzhou recipients and the Chengdu
recipients after LDLT and DDLT were all similar. CONCLUSION: Using well-studied
selection criteria, LDLT offers similar outcomes to DDLT for patient with HCC,
even using expanded selection criteria.
PMID- 26430400
TI - The effectiveness of trendelenburg positioning on the cross-sectional area of the
right internal jugular vein in obese patients.
AB - OBJECTIVE: Trendelenburg positioning is a common approach used during internal
jugular vein (IJV) cannulation. No evidence indicates that Trendelenburg
positioning significantly increases the cross-sectional area (CSA) of the IJV in
obese patients. The primary aim of this study was to determine the effectiveness
of Trendelenburg positioning on the CSA of the right internal jugular vein
assessed with ultrasound measurement in obese patients. METHODS: Forty American
Society of Anesthesiologists II patients with body mass index >=30 kg/m(2)
undergoing various elective surgeries under general endotracheal anesthesia were
enrolled. Ultrasound images of the right IJV were obtained in a transverse
orientation at the cricoid level. We measured the CSA of the right IJV two
different conditions in a sealed envelope were applied in random order: State 0,
table flat (no tilt), with the patients in the supine position, and State T, in
which the operating table was tilted 20 degrees to the Trendelenburg position.
RESULTS: The change in the CSA of the IJV from the supine to the Trendelenburg
position (1.80 cm(2) vs 2.08cm(2)) was not significantly different. The CSA was
paradoxically decreased in 10 of 36 patients when the position changed from State
0 to State T. CONCLUSIONS: Trendelenburg positioning does not significantly
increase the mean CSA of the right IJV in obese patients. In fact, in some
patients, this position decreases the CSA. The use of the Trendelenburg position
for IJV cannulation in obese patients can no longer be supported.
PMID- 26430401
TI - Occupational lead toxicity in battery workers.
AB - OBJECTIVE: To estimate blood lead level (BLL) and to assess the features of lead
toxicity among lead acid battery (LAB) industrial workers. METHODS: This
prospective study was carried out in the medical centre of PCSIR Laboratories,
Karachi from March 2012 - March 2013. Fifty LAB industry workers, males and
females between 17-65 years were included in the study. They were divided into
group 1 with 40 workers- directly related and group 2 with 10 workers -indirectly
related, (administration staff members) to LAB manufacture. Detailed history,
complete physical examination and BLL estimation by flameless atomic absorption
spectrophotometer was done. RESULTS: Total 34 patients in group 1 and 3 patients
in group 2 had elevated BLL. Comparison of group 1 and 2 revealed anemia
(40v/s4), bone pain (38v/s7), abdominal pain (38 v/s 2), nausea (32v/s6), head
ache & irritability (24v/s6), weakness & lethargy (21v/s6), tremors (13v/s0)
insomnia (5v/s4), lead line (4v/s 0) and blood pressure above 140/90 mm of Hg
(12v/s0) respectively. CONCLUSION: High blood lead level and features
attributable to lead toxicity were prevalent among LAB industry workers of
Karachi.
PMID- 26430402
TI - Is Gemcitabine and Cisplatin Induction Chemotherapy Superior in Locoregionally
Advanced Nasopharyngeal Carcinoma?
AB - OBJECTIVE: To investigate the outcome of locoregionally advanced nasopharyngeal
carcinoma (NPC) treated with induction chemotherapy followed by
chemoradiotherapy. METHODS: Between June 2005 and October 2007, 604 patients with
locoregionally advanced NPC were analyzed, of whom 399 and 205 were treated with
conventional radiotherapy and intensity-modulated radiotherapy (IMRT)
respectively. Meanwhile, 153 patients received concurrent chemotherapy, and 520
were given induction chemotherapy. RESULTS: With a median follow-up time of 65
months, the 3-, and 5-year overall survival (OS), locoregional free survival
(LRFS), and distant-metastasis free survival (DMFS) rates were 82.5% vs. 72.6%,
90.6% vs. 87.1%, and 82.5% vs. 81.2%, respectively. Induction chemotherapy was
not an independent prognostic factor for OS (P=0.193) or LRFS, but there was a
positive tendency for DMFS (P=0.088). GP regimen (gemcitabine + cisplatin) was an
independent prognostic factor for OS (P = 0.038) and it had a trend toward
improved DMFS (P = 0.109). TP regimen (taxol + cisplatin) was only a significant
prognostic factor for DMFS (P =0.038). CONCLUSIONS: Adding induction chemotherapy
had no survival benefit, but GP regimen benefited overall survival and had a
trend toward improved DMFS. GP regimen may be superior to TP/FP regimen
(fluorouracil + cisplatin) in treating locoregionally advanced NPC.
PMID- 26430403
TI - The effects of blood transfusion on renal functions in orthopaedic surgery.
AB - OBJECTIVE: The effects of perioperative blood transfusion on renal functions have
been studied in various studies. In this study, we investigated the effects of
blood transfusion on postoperative kidney functions in patients who underwent
orthopaedic surgeries. METHOD: Total 136 patients who were operated for several
orthopedic pathologies between June 2013 and December 2014 were evaluated. The
patients were divided into two groups according to the amounts of blood
transfusion. Ninety five patients (69.8%) who were transfused less than 3 units
were included in Group 1 and 41 patients (30.2%) who received 3 and more units of
blood were included in Group 2. RESULTS: There were no statistical difference
between the two groups in terms of preoperative gender, hypertension, diabetes
mellitus, chronical renal failure and smoking habbits (P > 0.05). No statistical
differences between the groups were seen in terms of postoperative hospital stay,
pulmonary and other complications as well as mortality (P > 0.05). When the two
groups were compared for blood parameters showing postoperative renal and other
system functions, no statistical differences were detected (P > 0.05).
CONCLUSION: Blood transfusion does not have negative effects on postoperative BUN
and creatinine levels in patients operated for orthopaedic pathologies.
PMID- 26430404
TI - Influenza and respiratory syncytial viruses: Efficacy of different diagnostic
assays.
AB - OBJECTIVE: To determine the efficacy of cell culture, immunoflourescence Assay
(IFA) and real time polymerase chain reaction (rRT-PCR) in relation to diagnosis
of influenza and Respiratory Syncytial Virus (RSV). METHODS: Total 2781 specimens
of throat swabs and nasopharyngeal aspirates were obtained from patients
suspected of respiratory viruses' infections from January 2009 to December 2011
at Universiti Kebangsaan Malaysia Medical Centre(UKMMC). The specimens were
processed by cell culture and immunoflurescence assay (IFA) and (rRT-PCR).
RESULTS: Thirty three (1.19%) specimens were positive for influenza virus A and
42 (1.51%) were positive for RSV by cell culture and IFA. On the other hand, rRT
PCR was able to identify 189 of 505 (37.43%) specimens in which 65 were influenza
A virus and 124 were RSV. Sensitivity of rRT-PCR was 100% for both influenza A
virus and RSV and specificity was 88% and 77% for influenza A virus and RSV,
respectively. CONCLUSION: rRT-PCR diagnosed respiratory viruses in shorter time
with a high level of sensitivity in comparison to conventional assays - cell
culture and IFA. These advantages help in managing patients by saving cost and
hospitalization stay.
PMID- 26430405
TI - Practices and challenges of infectious waste management: A qualitative
descriptive study from tertiary care hospitals in Pakistan.
AB - BACKGROUND AND OBJECTIVE: Infectious waste management practices among health care
workers in the tertiary care hospitals have been questionable. The study intended
to identify issues that impede a proper infectious waste management. METHODS:
Besides direct observation, in-depths interviews were conducted with the hospital
administrators and senior management involved in healthcare waste management
during March 2014. We looked at the processes related to segregation, collection,
storage and disposal of hospital waste, and identified variety of issues in all
the steps. RESULTS: Serious gaps and deficiencies were observed related to
segregation, collection, storage and disposal of the hospital wastes, hence
proving to be hazardous to the patients as well as the visitors. Poor safety,
insufficient budget, lack of trainings, weak monitoring and supervision, and poor
coordination has eventually resulted in improper waste management in the tertiary
hospitals of Rawalpindi. CONCLUSION: Study has concluded that the poor resources
and lack of healthcare worker's training in infectious waste results in poor
waste management at hospitals.
PMID- 26430406
TI - Readiness for Self-Directed learning among first year Saudi Medical students: A
descriptive study.
AB - OBJECTIVES: The objectives of the present study was to explore the readiness for
Self Directed Learning (SDL) among first year Saudi Medical students enrolled at
King Saud University (KSU) and Princess NourahBintAbdulrahman University (PNU) in
Saudi Arabia. METHODS: First year medical students were invited to participate in
a descriptive cross sectional study design. Data were collected using a Self
Directed Learner Readiness Scale (SDLRS) which is a self- assessment tool aimed
to assess three main components: self-management, desire for learning and self
control. The students responded to each item of the SDLRS on a 5-point Likert
scale. Data were analyzed using SPSS, mean, median and total scores were
calculated and were compared among student's groups. RESULTS: The mean score for
the desire of learning was the highest (4.08+/- 0.5) of all the three components
of the SDLRS followed by self-control (3.9+/- 0.9), while the least mean score
was for self-management (3.7+/-0.5). Overall, differences between student's
groups were not statistically significant. CONCLUSION: The present study revealed
that the overall SDL readiness of participants was good, students were highly
motivated for self-learning and had the ability for self-control. However, they
need assistance to improve their self-management skills.
PMID- 26430407
TI - Serum Levels of MDC and MMP-9 and the Relationship Between Serum Levels and
Disease Activity in the Patients with Systemic Lupus Erythematosus.
AB - BACKGROUND AND OBJECTIVE: Systemic lupus erythematosus (SLE) is a complicated
autoimmune disease. Although its pathogenesis is not clear, cytokine may be
involved in it. So we investigated serum levels of macrophage-derived chemokine
(MDC), and matrix metalloproteinase-9 (MMP-9), and to determine the relationship
between serum levels and the disease activity of SLE. METHODS: Serum levels of
MDC and MMP-9 were measured by enzyme-linked immuno sorbent assay (ELISA).
RESULTS: Significantly decreased serum levels of MDC and MMP-9 were found in SLE
as compared to those in controls (P<0.001 P<0.001), but serum levels of MDC and
MMP-9 increased after treatment (P<0.001 P<0.05). Serum levels of MDC and MMP-9
were lower in patients with active disease than those with inactive disease
(P<0.001 P<0.05). Significantly decreased serum levels of MDC and MMP-9 were
found in patients with renal damage than those without the damage (P<0.001
P<0.05). Serum level of MDC was lower in patients with arthritis than those
without the damage (P<0.001), but serum level of MMP-9 has no significant
difference in two groups (P>0.05). CONCLUSION: The present data suggest that MDC
and MMP-9 may be involved in the pathogenesis of SLE, and serum levels of MDC and
MMP-9 could be markers of monitoring disease activity, renal damage, disease
progression and improvement in SLE.
PMID- 26430408
TI - Prognostic factors for stereopsis in refractive accommodative esotropia.
AB - OBJECTIVE: To determine the prognostic factors affecting stereoacuity in patients
with refractive accommodative esotropia (RAE) according to the results of long
follow- up period. METHODS: We reviewed the charts of 70 patients with RAE
between the years 1985-2014. Patients were classified into three groups. G-1:
Stereoacuity score 40 second/arc. G-2: Stereoacuity score >40 second/arc (50
3000). G-3: No binocular vision. Initiation age of RAE, duration of deviation,
refractive error, amblyopia, amblyopia treatment, anisometropia, visual acuity,
family history, angle of deviation for distance and near at each group and the
prognostic factors affecting stereoacuity were analyzed. RESULTS: The mean
initiation age of RAE was 2.7+/-1.5 years, the mean age at first visit was 6.4+/
4.2 years. The mean follow up time was 7.3+/-4.4 years. Seven patients had 40
second/arc, 48 patients had 50 to 3000 second/arc stereoacuity, 15 patients had
no binocular vision. Mean deviation for near was statistically higher in group 2
and 3. Visual acuity levels were higher in group 1 and 2 and was statistically
significant. Low visual acuity (p=0.001, 0.008), higher angle of deviation at
near (p=0.01), increased duration of deviation (p=0.01), presence of amblyopia
(p=0.001) and irregularity of amblyopia treatment (p=0.01) were significantly
related with poor stereoacuity. CONCLUSION: According to the prognostic factors
low stereoacuity was mostly related with amblyopia as a result the late
presentation of the patients in seeking care. Appropriate treatment as full
refractive correction and amblyopia treatment during the RAE is important for
development of good stereopsis. Also angle of deviation at near and duration of
deviation can be a useful predictor for poor stereoacuity levels.
PMID- 26430409
TI - Comparison of higher order aberrations in patients with various refractive
errors.
AB - OBJECTIVE: To compare the mean root mean square (RMS) of total higher order
aberrations (HOAs), coma and spherical aberrations in individuals with myopia,
hypermetropia and myopic astigmatism. METHODS: This prospective analytical study
was conducted at Armed Forces Institute of Ophthalmology, Rawalpindi, Pakistan
from Jan 2014 to Dec 2014. Two hundred eyes of 121 patients with age ranging from
18-40 years were included in the study. Patients were divided into 4 group namely
Low myopia, High myopia, Astigmatism and Hypermetropia on the basis of refractive
error. Included were the patients who had refractive error more than +/- 0.5D and
best corrected visual acuity (BCVA) of 0.00 or better. Patients who had history
of surgery and / or eye disease were excluded from the study. Visual acuity (VA),
Spherical equivalent (SE) of refractive error, RMS value of total HOAs, coma and
spherical aberrations were evaluated. HOAs were measured with aberrometer
(Wavelight analyzer version 1073) at 6 mm pupil size. RESULTS: Age of the
patients ranged from 18 years to 40 years with mean age of 29.10+/-10.6 years.
Seventy one (35.5%) were males and 129 (64.5%) were female. Mean RMS value of
HOAs, coma and spherical aberrations was calculated in all four groups. RMS of
total HOAs and spherical aberrations in hypermetropia was 0.96+/-0.96 and 0.30+/
0.42 respectively and it was higher than other three groups. CONCLUSIONS: In
overall comparison the mean RMS of total HOAs and spherical aberrations was
significantly increased in hypermetropia group and there was a statistically
significant negative correlation of SE of hypermetropia with RMS of total HOAs
and spherical aberration.
PMID- 26430410
TI - Prevalence of obesity and hypertension among University students' and their
knowledge and attitude towards risk factors of Cardiovascular Disease (CVD) in
Jeddah, Saudi Arabia.
AB - OBJECTIVES: To investigate the prevalence of obesity and hypertension among
University students' and their knowledge and attitude towards risk factors of
cardiovascular disease (CVD) in Jeddah,: Saudi Arabia. METHODS: A total of 610
male students were selected for present cross sectional study and their blood
pressure (BP) and body mass index (BMI) was determined, other data was gathered
through a questionnaire, and SPSS-16 was used for analyzing data. RESULTS: Out of
610 students, 7.5% were hypertensive (systolic 2.6% and diastolic 6.3%) while the
BMI of 51.6% was in the normal range, 29.8% were overweight and 10.7% were
moderately obese and 7.9% were severely obese. Majority of the participants
considered that smoking, increased fatty food intake, obesity, high BP, and
increased LDL-cholesterol level, are the main causes of the CVD. Most of the
participants agreed that one should know his BP, blood sugar, serum cholesterol
and one should maintain normal body weight and should do regular exercise. They
were also aware that healthy lifestyle could prevent CVD. However, majority of
the participants were not practicing healthy lifestyle. CONCLUSION: A huge gap
exists in the knowledge, attitude and practice regarding risk factors of CVD
among the university students.
PMID- 26430411
TI - Psychosocial risk factors of myocardial infarction and adverse effects of
streptokinase in public sector hospitals.
AB - OBJECTIVES: This study investigated the psychosocial risk factors of myocardial
infarction and time related adverse effects of administration of streptokinase on
short-term morbidity and mortality in patients with ST-segment-elevation
myocardial infarction (STEMI). METHODS: One hundred patients with STEMI treated
with streptokinase in the hospital setting were prospectively enrolled in the
study. The primary outcome parameter was the incidence of major adverse cardiac
events. During hospital stay the psychosocial and demographic risk factors were
also investigated. RESULTS: The overall mortality rate was similar in both groups
and it was not significant. (5.7% vs 14.5%; P = 0.18). The number of recurrent
chest pain was significantly higher in the group 2 compared to the group 1 (25%
vs 62.5%; P = .01). The number of hypotesion was significantly higher in the
group 1 as compared to the group 2 (30.7% vs 6.2%; P = .009). The demographic and
psychosocial risk factors were recorded. CONCLUSIONS: The early intravenous
administration of streptokinase in the hospital setting leads to a reduced rate
of major cardiovascular events compared to delayed administration beyond 2 hours.
However, mortality rates were not significantly affected. Secondary prevention
should be targeted on modifiable demographic, dietary, and psychosocial risk
factors of STEMI.
PMID- 26430412
TI - Child sexual abuse among adolescents in southeast Nigeria: A concealed public
health behavioral issue.
AB - BACKGROUND AND OBJECTIVE: Child sexual abuse among adolescents is an often
overlooked issue in pediatrics, yet it is a major cause of low self esteem and
stigmatization in adolescents. The objective of this study was to determine the
socioeconomic determinant and pattern of child sexual abuse among adolescent
attending secondary schools in South East Nigeria. METHODS: This was a cross
sectional study that was carried out among children in three secondary schools in
Enugu and Ebonyi states of Nigeria. Five hundred and six adolescents who met
inclusion criteria were consecutively recruited into our prospective study
between June and October, 2014. RESULTS: One hundred and ninety nine (40 %) of
the respondents had been abused and the commonest form of abuse was to look at
pornographic pictures, drawings, films, videotapes or magazine 93(18.4%). Fifty
eight (11.5%) adolescents stated that they were abused once with age at first
exposure being 7-12 years 57 (11.4%). When grouped together, family members and
relatives are perpetrators of child sexual abuse. There was significant
difference in sex abuse between males and females (p=0.014) while there were no
significant difference for age (p=0.157) and social class (p=0.233). CONCLUSION:
Overall prevalence and one time prevalence rates of sexual abuse among
adolescents in south east Nigeria was 40% and 11.5% respectively with male
perpetrators. There is no link between socioeconomic class, age and child sexual
abuse among adolescents.
PMID- 26430413
TI - Acute Post Surgical Pain may result in chronic post surgical pain: A Systemic
Review and Meta Analysis.
AB - OBJECTIVE: Chronic post surgical pain (CPSP) occurres frequently (from 10% to
50%) and has serious effects on the mood and activities of patients. This study
was designed to evaluate the relationship between acute post surgical pain and
chronic post surgical pain. METHODS: Electronic search databases included PubMed,
EMBASE, Cochrane database and web of science. 9-stars Newcastle-Ottawa Scale was
used to evaluate the quality of included studies. The odds ratio was used as a
summary statistic index. Heterogeneity was assessed with I (2). RESULTS: We
collected data from 4 case-control studies with or without chronic post surgical
pain and compared those with patients who had acute post surgical pain or not.
The age, sex was controlled as confounding factors. We collected 765 patients
with chronic post surgical pain, of which 38.82% used to have acute post surgical
pain. The risk ratio of patients with acute post surgical pain, as compared with
no acute post surgical pain, was 3.10 for chronic post surgical pain (95% CI:
2.44, 3.96). CONCLUSION: Acute post surgical pain is a rick factor for chronic
post surgical pain. We need to pay much attention to this phenomenon. However,
more studies with high quality were still needed to confirm these findings.
PMID- 26430414
TI - The prevalence and causes of visual impairment in young Turkish men.
AB - OBJECTIVE: To explore the causes and prevalence of visual impairment in young
Turkish men. METHODS: The health examination data of the candidates that are
saved in National Defense Ministry of Turkey was used. The data of the candidates
examined between 1 January 2009 and 31 December 2011 were evaluated. The total
number of the candidates was 1777500. The candidates requiring advanced
examination are referred to secondary and tertiary examination hospitals.
RESULTS: Fourteen thousand eight hundred sixty two(14862) out of 1777500
candidates were declared unfit for compulsory military service because of
ophthalmic causes. The prevalence of ophthalmologic diseases causing unfitness
for military service was found 0.746% for 2009, 0.871% for 2010 and 0.889% for
2011. These included high refractive errors which was the most frequent pathology
causing unfitness (40.1%). Nonsurgical retina, vitreous and optic nerve diseases
were the most frequent cause of visual impairment (0.212%). Corneal and lens
pathologies were the second most frequent cause of blindness (0.101%).
CONCLUSIONS: The data bank in National Defense Ministry analyzed in this study is
not directly intended to explore the causes and prevalence of visual impairment
in Turkey. However this study gives considerable knowledge about the causes and
prevalence of visual impairment in Turkey.
PMID- 26430415
TI - Response Guided Interferon Therapy for Genotype 3 of Chronic Hepatitis C:
Compliance and Outcome.
AB - OBJECTIVE: To determine compliance and improvement in sustained viral response
(SVR) by following response guided therapy (RGT) plan of interferon and
ribavirin, for genotype 3 in chronic hepatitis C. METHODS: Patients with chronic
hepatitis C genotype 3, who were eligible for interferon-ribavirin therapy and
consented for RGT, were included. Those with no rapid viral response (RVR),
having coarse echotexture of liver or undergoing re-treatment, were advised 48
week treatment whereas, rest had 24 week standard therapy. PCR for HCV RNA
checked 6 months after discontinuing treatment, was the primary end point of
study. RESULTS: Of 154 patients, included in the study with mean age of 39.9 (+/
10.84) and male to female ratio 1.4/1 (94/60), majority of patients, 136 (88.4%)
were treatment naive whereas, 18 (11.6%) were being retreated. On ultrasound, 63
(40.9%) patients had coarse liver and 33 (21.4%) had splenomegaly. RVR was
achieved in 99 (64.3%) patients. Overall 66(42.8%) patients merited extended
duration of therapy as per RGT plan but only 22 (33%) were compliant. Treatment
related side effects were the dominant reason for declining RGT in 33 (75%)
patients. SVR was noted in 111 (72.1%) patients. Those patients with extended
therapy (RGT), had SVR 90.9% (20/22), although, better but statistically not
significant than those who stopped therapy at 6 months 77.2% (34/44) (p value
0.11). CONCLUSION: Response guided therapy plan did not improve SVR to
pegylatedinterferon and ribavirin therapy in patients with genotype 3 and it has
low patient compliance due to treatment related side effects.
PMID- 26430416
TI - Knowledge and practice of implant-retained restorations among dental students in
Saudi Arabia.
AB - OBJECTIVES: The aim of the study was to assess the knowledge and practice of
implant retained restorations (IRR) among senior dental students in Saudi Arabia.
METHODS: Four hundred questionnaires were distributed among senior dental
students of five dental schools in Saudi Arabia. Student's knowledge was assessed
regarding which implant restoration [cement retained restoration (CRR) or screw
retained restoration (SRR)] better provides the desired clinical properties.
Students' practice of IRR, perception of their knowledge and need for further
education related to IRR were also assessed. Descriptive statistics and chi
square test were employed to assess collected data. RESULTS: Three hundred and
fifty four senior dental students responded at a response rate of 88.5%. Thirty
three percent respondents did not have any practical experience of IRR. Students
showed a clear preference for CRR with regards to aesthetics (71.4%), passive fit
(55.3%), fabrication ease (57.3%) and fracture resistance (40%). SRR were
considered to provide better retention (59.6%), soft tissue health (51.1%) and
ease of retrievability (72%). Nearly 40% of students agreed that they did not get
sufficient information related to IRR in undergraduate courses. CONCLUSIONS:
Clinical training of IRR is compromised in the undergraduate curriculum in dental
schools of Saudi Arabia. The knowledge of dental students regarding IRR was
broadly in line with current evidence.
PMID- 26430417
TI - Effect of different pH solvents on micro-hardness and surface topography of
dental nano-composite: An in vitro analysis.
AB - OBJECTIVE: Erosion of tooth surface is attributed to recent shift in diet pattern
and frequent use of beverages. The aim of this research was to evaluate the
effects of different beverages on surface topography and hardness of nano-filled
composite material. METHODS: Sixty flat disc shaped resin composite samples were
fabricated and placed in distilled water for 24 hours. After 24 hours test
samples were dried and divided into 4 groups. Group A (n=15) specimens were
placed in tight amber bottle comprising 25 ml of artificial saliva. Similarly
Group B, C and D were stored in equal amounts of orange juice, milk and coca cola
drink respectively. Samples were checked for hardness and surface changes were
evaluated with scanning electron microscopy. RESULTS: There were strong
significant difference observed in samples immersed in orange juice and
artificial saliva. A strong significant difference was seen between Group D and
Group A. Group A and Group C showed no significant difference. The micro-hardness
test showed reduced values among all samples. CONCLUSION: Beverages consumed
daily have a negative influence on hardness and surface degradation of nano
filled dental composite. Comparatively, nano-filled composites possess higher
surface area to volume ratio of their fillers particle size may lead to higher
surface roughness than other resin based dental biomaterials.
PMID- 26430418
TI - Dietary Practices in Saudi Cerebral Palsy Children.
AB - OBJECTIVES: To determine the dietary practices of Saudi cerebral palsy (CP)
children. METHODS: A self-administered questionnaire was used to collect the
following information from parents of CP children: demographics, main source of
dietary information, frequency of main meals, foods/drinks used for main meals
and in-between-meals. RESULTS: Parents of 157 CP children participated. Parents
were divided into three, while children were divided into two age groups. The
main sources of dietary information included popular media (46.5%) and dentist
(36.3%). Most of the children had three meals (71.3%) or two meals (24.8%) daily.
Choices for main meals included meats (68.8%), vegetables (65.6%), fruits (28.4%)
and puddings (38.9%). The main three drinks choices with main meals included
packed juices (59.9%), bottled water (58.8%) and fresh fruit juices (33.1%). The
choices for in-between meals snacks included biscuits (61.1%), potato chips
(51.6%), fruits (43.9%) and chocolates (41.4%). The choice of drinks with snacks
was similar to that used with main meals. In cross-tabulation, older parents used
meat (p=.03) and soft drinks (p=.04) more often for their children's main meals.
Older children were given meat (p=.004) and soft drinks (p=.04) more often with
main meals. Older children were given potato chips as snacks more often than
younger children (p=.02), and there was a trend towards use of chocolates as
snacks in older children (p=.08). CONCLUSION: Parents of CP children need to be
educated about dietary practices of their children especially in areas such as
the use of packed juices, dairy products, soft drinks and chocolates.
PMID- 26430419
TI - Prevalence of celiac disease in adult type 1 patients with diabetes.
AB - OBJECTIVES: Celiac disease, an autoimmune disease, is related to immune mediated
intolerance to gluten. Some studies suggest that Celiac Disease was 20 times more
frequent in type 1 patients with diabetes. The objective of our study was to
evaluate the prevalence of celiac disease in hospital based type 1 diabetic
adults. METHODS: Our study was carried out retrospectively in Medeniyet
University Goztepe Training and Educational Hospital in Istanbul between 2012
2013. The cohort comprised 482 type 1 patients with diabetes attending the
diabetes outpatient clinic. The data were analyzed by SPSS 10.5 package program.
Student's t tests is used for comparative analyses. A p-value less than 0.05 was
considered statistically significant. RESULTS: The cohort included 482 type 1
patients with diabetes. Fifty seven of them were not evaluated for Endomysium
antibody positivity. Fifteen of the remaining 425 patients were positive for anti
endomysial antibody (3.5%). The prevalence of biopsy proven celiac disease was
2.3% (10/425). There was no significant difference between Endomysial antibody
positive and negative groups in regard of age, sex, or duration of the disease.
CONCLUSION: This study confirms that the celiac disease is common in type 1
diabetic patients. Since a small proportion of celiac patients are symptomatic
this disorder should be screened in all adult type 1 patients with diabetes by
antiendomysium antibody.
PMID- 26430420
TI - Correlation between uterine fibroids with various magnetic resonance imaging
features and therapeutic effects of high-intensity focused ultrasound ablation.
AB - OBJECTIVE: To explore the correlation between magnetic resonance imaging (MRI)
features of uterine fibroids (UFs) and therapeutic effects of high-intensity
focused ultrasound ablation (HIFUA), and to provide evidence for UFs diagnosis
with MRI in clinical practice. METHODS: Forty-three UFs patients who were treated
in our hospital from April 2012 to June 2014 were selected, including 72 UFs (48
multiple and 24 single UFs). Transverse, sagittal and coronal MRI scanning was
performed one week before and after HIFUA to record UF number, location, type
(intramural fibroid, submucosal fibroid and subserosal fibroid), mean diameter,
hemoperfusion state, volume and ablation rate. The patients were followed up in
the postoperative 1st, 2nd and 3rd months. RESULTS: HIFUA exerted the best
ablative effect on fibroids on the anterior uterine wall (F=26.763, P=0.036).
Various types of fibroids were ablated significantly differently (F=3.406,
P<0.05) by HIFUA that was most effective for ablating the subserosal ones. Having
significantly different ablative effects on UFs with different radial line
lengths (F=29.94, P<0.05), HIFUA ablated those with radial line lengths of 3-5 cm
most effectively. For UFs with different T2WI signal intensities, HIFUA also
functioned significantly differently (F=3.179, P=0. 03). CONCLUSION: HIFUA
exerted significantly different ablative effects on UFs with various MRI
features. Therefore, these features were well correlated with the therapeutic
effects of HIFUA, allowing MRI as a promising diagnostic protocol.
PMID- 26430421
TI - Brief culturally adapted cognitive behaviour therapy for obsessive compulsive
disorder: A pilot study.
AB - OBJECTIVE: To demonstrate the effectiveness of Brief Culturally adapted Cognitive
Behavior Therapy (CaCBT) in the treatment of Obsessive Compulsive Disorder (OCD).
METHODS: This pre and post design study was conducted on out-patients with OCD at
Centre for Cognitive Behaviour Therapy, Fountain House, Lahore, from April 2011
to April 2012. A semi structured questionnaire was developed to document
demographic details of all the patients. All the participants were assessed at
baseline (Pre Therapy session) with Yale Brown Obsessive Compulsive Disorder
Scale (Y-BOCS), Hospital Anxiety & Depression Scale (Depression Subscale &
Anxiety Subscale) and Brief Disability Questionnaire (BDQ). They were re-assessed
on the same scales at the end of therapy in a follow up assessment session.
Feedback from patients and their family member, who were trained as co-therapist,
was obtained at the end of the therapy for assessing the satisfaction with the
therapy. All the patients received six sessions of brief culturally adapted
cognitive behavior therapy (CaCBT). Statistical analyses were carried out using
SPSS v.22. RESULTS: The mean age of the sample (n=21) was 31.14+/-11.9 years.
There were significant differences post CBT between the scores of Y-BOCS
(p=0.000), HADS - Depression subscale (p=0.001), HADS - Anxiety subscale
(p=0.000) and BDQ (p=0.000). CONCLUSION: This study provides preliminary evidence
for effectiveness of culturally adapted CBT for OCD.
PMID- 26430422
TI - Estrogen Receptor Alpha (ESR1) Gene Polymorphisms in Pre-eclamptic Saudi
Patients.
AB - OBJECTIVES: Pre-eclampsia causes maternal mortality worldwide. Estrogen receptor
alpha (ESR1) gene polymorphisms were responsible for cardiovascular diseases.
This case control study was conducted to investigate whether 2 polymorphic genes
of ESR1 are associated with pre-eclampsia among Saudi women in Madina city, Saudi
Arabia. METHODS: Blood samples from 97 pre-eclamptic and 94 healthy pregnant
women were analyzed using restriction fragment length polymorphism-polymerase
chain reaction method. All the subjects were recruited randomly from outpatient
clinics of Madina Maternity Children Hospital (MMCH), Madina, Saudi Arabia,
between Dec. 2012 and Jan. 2014. RESULTS: There was no association between pre
eclampsia and PvuII and XbaI ESR1 gene polymorphisms individually. TT/AA and
TT/AG genotype combination existed significantly in pre-eclamptic patients
compared to control. The frequency of PvuII and XbaI combined TT/AA genotypes
between pre-eclamptic women was 36.1% vs 9.6%, however, frequency of PvuII and
XbaI combined TT/AG genotypes between pre-eclamptic women was 3.1% vs 17%,
compared to control. The homozygous T-A haplotype carriers showed high pre
eclampsia risk, independent of pregnancy, BMI and smoking status (adjusted odds
ratio (OR): 3.26, 95% confidence interval (CI):1.71-9.21). The heterozygous T-A
haplotype carriers did not differ from that of non-carriers (adjusted OR: 1.12,
95% CI: 0.47-2.75). No association was observed between pre-eclampsia and T-G, C
G and C-A haplotype of PvuII and XbaIESR1 gene polymorphisms. CONCLUSIONS: T-A
haplotype of homozygous associated with pre eclampsia not heterozygous carriers
of ESR 1 PvuII and XbaI gene polymorphisms elicited high risk of pre-eclampsia.
GG genotype of XbaI polymorphism decreased pre-eclampsia risk. Further studies
using larger sample size are recommended to investigate the ESR 1 gene
polymorphisms associated with pre-eclampsia.
PMID- 26430423
TI - Gender difference in components of metabolic syndrome among patients of type 2
diabetes.
AB - BACKGROUND AND OBJECTIVES: Diabetes mellitus, hypertension, obesity and
dyslipidemia are the integral components that constitute metabolic syndrome. It
has emerged as cause of substantial mortality with gender difference. To compare
the gender characteristics of metabolic syndrome in subjects of type 2 diabetes
mellitus. METHODS: This observational comparative prospective study was conducted
in medical ward of BVH Bahawalpur over period of 6 month from January 2014 to
June 2014. Sample size of 100 diagnosed cases of type 2 diabetics (comprising
equal number of males and females) were collected. As defined by WHO and IDF,
variables of metabolic syndrome studied were BMI, hypertension, hyperglycemia and
hyperlipidemia. The lipid values were interpreted in normal or high risk category
by applying NCEP ATPIII criterion. Fasting sample were collected for sugar and
lipid profile. Anthropometric, demographic and biochemical data was tabulated.
Continuous and categorical variables were displayed as mean +/- standard
deviation and percentage respectively. Student 't' test was use to assess the
difference for the lipid profile at 5% significance level. RESULTS: Female
patients were found to be overweight, hypertensive and had uncontrolled
hyperglycemia as compared to male subjects. Their systolic blood pressure was
150+/-25.75 and diastolic was 90+/-17mm/hg. The mean blood glucose concentration
was 246.64+/-105mg/dl. In age group 35-44 years, the mean triglycerides and
cholesterol levels in females were 184.54+/-42.05 and 192.5+/-34mg/dl
respectively. HDL-C was 33.2+/-5.19mg/dl. In females with age group of 45-54
years, the mean concentration of triglycerides, total cholesterol and HDL-C were
217.75+/-77.6mg/dl, 190.95+/-14.4mg/dl and 31.75+/-3.8mg/dl respectively, and all
were in high risk category when compared to cut off values determined by
NCEP/ADA. While in females of age group 55-64 years, the values of TGs, total
cholesterol and HDL-C were 204+/-154.11mg/dl, 200.09+/- 47.8 mg/dl and 33.4+/
4.6mg/dl respectively and again all these values were significantly raised.
CONCLUSION: Female genders were affected in all respects. They had higher BMI,
hypertension, hyperglycemia and hyperlipidemia as compared to male counterparts.
PMID- 26430424
TI - Histopathological examination of appendicectomy specimens at a district hospital
of Saudi Arabia.
AB - BACKGROUND AND OBJECTIVE: Appendicectomy for acute appendicitis is one of the
most commonly performed surgical procedures. Acute appendicitis has remained a
clinical entity and an ongoing diagnostic challenge. A retrospective study was
performed to determine histological diagnosis, demographic data, the rate of
perforated appendicitis and negative appendicectomies. METHODS: Histopathological
records of 480 resected appendices submitted to histopathology department at Arar
Central Hospital in the Northern Border Province of Saudi Arabia over the period
of 3 years from July 2011 to June 2014 were reviewed retrospectively, to
determine acute appendicitis, complication (gangrene, perforation) rate, negative
appendicectomy rate, histopathological diagnosis and unusual finding on
histology. RESULTS: Out of 480 specimens of appendix, appendicitis accounted for
466 (97.0%) with peak occurrence in the age group of 11 to 50 years in male and
11 to 40 years in female. Histopathological diagnosis include acute appendicitis
250 (52.0%), suppurative appendicitis 135 (28.0%) acute gangrenous appendicitis
60 (12.5%), perforated appendicitis 9 (2.0%), chronic appendicitis 12 (2.5%).
Negative appendicectomy rate was 14 (3%) and two time more common in female with
peak occurrence in the age group of 20-30 yrs. There was no unusual histological
finding like carcinoid tumour of appendix. CONCLUSION: The present study showed a
high number of appendicitis in adolescents and young adults. Negative
appendectomy was more common in females. The study support routine histological
examination of all the appendicectomy specimens to avoid missing of any
clinically important and treatable condition.
PMID- 26430425
TI - Frequency of Hepatitis-B and C in patients undergoing cataract surgery in a
tertiary care Centre.
AB - OBJECTIVE: To analyze the frequency of hepatitis B and C in patients undergoing
cataract surgery. METHODS: This descriptive study was conducted at department of
Ophthalmology Jinnah Post Graduate Medical Centre. The duration of study was
seven months from May 2013 to November 2013. After taking informed consent from
the patient and hospital ethical committee all patients presenting with cataract
and undergoing cataract surgery were evaluated for the existence of hepatitis C
and B. Diagnosis of hepatitis C or B was made on the criteria that a patient must
be positive for either Anti-HCV or HBsAg or both. Proformas were filled and data
was collected and analysis was done. Pearson's correlation coefficients were
calculated to calculate the occurrence of hepatitis C and B in general population
undergoing cataract surgery. RESULTS: Six hundred and forty-eight patients were
operated on for cataract surgery at Jinnah Post Graduate Medical Centre during
the study period. Mean age of patients was 63 years, 300 (46.29%) were male and
348 (53.70%) female. Out of them 57 (8.79%) patients were carriers of either
Hepatitis C or B. Hepatitis B accounted for 17 cases (2.62%) however Hepatitis C
positive were 40 cases (6.17%). Nobody was simultaneously affected by both
hepatitis C and B. CONCLUSION: Significant number of asymptomatic carriers of
hepatitis C and B were found in preoperative cataract patients. It is recommended
that preoperative screening of all cataract patients should be done so that
asymptomatic carriers might not become a threat for spread of disease.
PMID- 26430426
TI - Diagnostic value of urinary protein and creatinine in combination with renal
ultrasound examination in early renal damage of patients with hypertension.
AB - OBJECTIVE: To evaluate the diagnostic value of urinary protein and creatinine in
combination with renal Doppler ultrasound examination in early renal damage of
patients with hypertension. METHODS: One hundred twenty two hypertensive patients
who were treated in our hospital from December 2013 to June 2014 were selected
for this study, including 33, 41 and 48 cases of Stage I, Stage II and Stage III
hypertension respectively. Meanwhile, 30 healthy subjects were selected as the
control group. They received urinary protein, creatinine and renal Doppler
ultrasound examination. RESULTS: The urinary protein levels of Stage I, II and
Stage III hypertensive patients were significantly different from that of the
control group (p<0.05). Urinary creatinine levels were similar (p>0.05) in stage
I and II but different from control (p<0.05) in stage III. Doppler ultrasound
examination showed that Stage I hypertensive patients had similar renal longest
diameter (RLD), renal parenchymal thickness (RPT) and ratio of RPT/renal sinus
thickness to those of the control group (p>0.05), and RLDs of Stage II
hypertensive patients and the control group were not significantly different
(p>0.05). CONCLUSION: Urinary protein and creatinine levels in combination with
renal Doppler ultrasound examination could diagnose early renal damage in
patients with hypertension.
PMID- 26430427
TI - Caudal ropivacaine and bupivacaine for postoperative analgesia in infants
undergoing lower abdominal surgery.
AB - OBJECTIVE: To compare the postoperative analgesic efficacy of ropivacaine 0.175%
and bupivacaine 0.175% injected caudally into infants for lower abdominal
surgery. METHODS: Eighty infants, aged 3-12 months, ASA I-II scheduled to undergo
lower abdominal surgery were randomly allocated to one of the two groups: Group R
received 1ml.kg(-1) 0.175% ropivacaine and Group B received 1ml.kg(-1) 0.175%
bupivacaine via caudal route. Postoperative analgesia, sedation and motor block
were evaluated with modified objective pain scale, three-point scale and modified
Bromage scale respectively. Postoperative measurements including mean arterial
pressure (MAP), heart rate (HR), pain (OPS), sedation and motor block score were
recorded for four hours in the postoperative recovery room. Parents were
contacted by telephone after 24 hours to question duration of analgesia and side
effects. RESULTS: No significant differences were found among the groups in
demographic data, MAP, HR, OPS and sedation scores during four hours
postoperatively. The duration of analgesia was 527.5+/-150.62 minutes in Group R,
692.77+/-139.01 minutes in Group B (p=0.004). Twelve (30%) patients in Group R,
16 (40%) patients in groupB needed rescue analgesics (p=0.348). Rescue analgesics
were administered (1 time/2 times) (9/3) (22.5/7.5%) in Group R and 16/0 (40/0%)
in Group B, where no statistically significant difference was determined between
the groups (p=0.071). Motor blockade was observed in 7 (17.5%) patients in Group
R, and 8 (20%) patients in Group B (p=0.774). CONCLUSION: This study indicated,
that a concentration of 0.175% ropivacaine and 0.175% bupivacaine administered to
the infants via caudal route both provided effective and similar postoperative
pain relief in infants, who underwent lower abdominal surgery.
PMID- 26430428
TI - Early outcome of Coronary Artery Bypass Graft Surgery in patients with
significant Left Main Stem stenosis at a tertiary cardiac care center.
AB - OBJECTIVE: Primary objective of this study was to evaluate the impact of
significant left main stem (LMS) stenosis on the early outcome of coronary artery
bypass graft (CABG) surgery. METHODS: A Retrospective non-randomized analytical
study was conducted in Cardiac surgery department, Chaudhary Pervaiz Elahi
Institute of Cardiology (CPEIC) Multan, Pakistan. The data of patients who
underwent isolated CABG at our institution from February 2008 to March 2014 were
analyzed. Two thousand six hundred two (2602) patients of isolated CABG were
divided into 2 groups according to the LMS disease. Group I (n=2088): without
significant LMS disease and Group II (n=514): with LMS disease. Data was analyzed
using SPSS V16. The groups were compared using Student's t-test for numeric
variables. Chi-square test and Fishers Exact test were used for categorical
variables. P-value <= 0.05 was considered as significant difference. RESULTS: Out
of two thousand six hundred two, 2088 patients were in Non.LMS group (Control
Group) and five hundred fourteen were in LMS Group (Study Group). Patients with
LMS disease were older. In both groups there was no statistically significant
difference regarding gender distribution, risk factors of IHD, pre-operative
renal function and preoperative CKMB levels. Significant number 50 (9.7%) of
patients were unstable in LMS group and they needed urgent surgery (p-value
<0.0001). Need and duration for inotropic support and intra-aortic balloon
counter-pulsation support were significantly high in LMS group (p-value <0.0001,
0.002, 0.003 respectively). Similarly Mechanical ventilation time and hospital
stay were higher in LMS group. Incidence of pulmonary complications and operative
mortality were significantly higher in LMS group (p-value 0.005 and 0.001
respectively). Mortality of CABG patients with significant left main coronary
stenosis was 13 out of five hundred fourteen (2.5%) as compared to just 17 out of
two thousand eighty eight (0.8%) in control group. CONCLUSION: This study showed
that significant LMS disease is an independent risk factor for early
cardiopulmonary morbidity and mortality after CABG surgery.
PMID- 26430429
TI - Thyroid function status and its impact on clinical outcome in patients admitted
to critical care.
AB - OBJECTIVE: To analyze alterations in thyroid function and the correlation between
results of thyroid function test and mortality in medical and surgical intensive
care unit (ICU) patients. It also aimed to evaluate the effect of thyroid
dysfunction in ICU patients and their need for mechanical ventilation (MV).
METHODS: A single-center, prospective, observational study was conducted on
patients admitted to medical and surgical ICU between 2013-2014.. Clinical and
paraclinical findings (free triiodothyronine, free thyroxine and thyroid
stimulating hormone) were documented for all patients. Regression analysis and
chi-square were used for death and MV outcome variables. RESULTS: We included 502
patients. Of these, 340 (67.7%) were admitted to the medical ICU. Results of
thyroid function tests were normal in 320 (64%) and 162 (32.3%) medical and
surgical ICU patients, respectively. Euthyroid sick syndrome (ESS) was documented
in 86 patients (17%). Mortality was twice higher among surgical ICU patients with
ESS compared to those with normal thyroid function (p=0.085), which is not
statistically significant. Based on thyroid function status, no differences in
the risk to be mechanically ventilated was found between medical or surgical ICU
patients. CONCLUSION: There is a significant association between ESS and
mortality in ICU patients. Future studies should determine whether abnormal
thyroid function increases the risk for MV in ICU patients.
PMID- 26430430
TI - Analysis of uterine rupture at university teaching hospital Pakistan.
AB - OBJECTIVE: To determine the risk factors, management modalities, fetomaternal
outcome of uterine rupture cases at University teaching hospital in Pakistan.
METHODS: This retrospective descriptive study was conducted at the Department of
Gynaecology and Obstetrics Liaquat University of Medical and Health Sciences
(LUMHS) for a period of one year from January 1st to December 31st 2012. Main
outcome measures were frequency, age, parity, booking status, risk factors,
management modalities, fetal and maternal mortality associated with uterine
rupture. The data was collected on pre-designed proforma analysed using SPSS
Version 16 statistical package. RESULTS: The frequency of ruptured uteri was
calculated to be 0.67%, giving a ratio of 1:148 deliveries. Highest incidence was
found in age group 25-30 (44.26%) with mean age of 30.36 years. and parity group
2-3 (57.37%) with mean parity 4.08. The risk factors for ruptured uterus include
Caesarean section 43(70.49%), injudicious use of oxytocin 33(54.09%), obstructed
labour 15 (24.59%) and multiparty 18 (29.50%). Repair of uterus was performed in
47(77.04%) cases. Maternal case fatality was 5(8.19%), while foetal wastage was
51 (83.60%). CONCLUSION: This study confirms the existence of a serious
preventable obstetric problem, with significant maternal mortality and foetal
wastage. Integrated efforts include Health education, focused antenatal care,
skilled attendance, avoidance of injudicious use of oxytocin, and need of
hospital based deliveries in patients with caesarean section which should be
intensified to reduce this drastic obstetrical complication.
PMID- 26430431
TI - Diagnosis and treatment of acute urogenital and genitalia tract traumas: 10-year
clinical experience.
AB - OBJECTIVE: To report our 10-year diagnosis and treatment experience of acute
urogenital and genitalia tract traumas and outline the management of the
traumatic injury. METHODS: We reviewed the diagnoses and treatments of 208 cases
of acute kidney, ureter, bladder, urethra, or male genitalia injuries in our
department between March 2002 and March 2012. The patient data including general
information, injury position and mechanism, diagnosis and treatment, the follow
up information was analyzed and summarized. RESULTS: Of 62 patients with renal
injury examined by ultrasound and computed tomography (CT) examination, 45 were
treated conservatively, 9 with superselective arterial embolization, and 8 with
nephrectomy. Intravenous pyelogram (IVP) was conducted in two patients with
ureteral injury, one was treated with cystoscopic ureteral catheterization and
the other with ureteric reimplantation. Bladder injury (6 patients) confirmed
with a waterflood susceptibility test combined with CT scans underwent laparotomy
and the bladder suturing was done. Of 92 patients with urethral injury, 6 were
treated with a nonoperative approach (indwelling catheter), 18 with urethral
realignment, 35 with cystoscopic urethral realignment, 29 with end-to-end
anastomotic urethroplasty, and 4 with urethral repairmen. Of the 24 cases with
penile injuries, 1 underwent conservative treatment, 8 were treated with
debridement and suture ligation, and 15 were managed with suture repair of the
penis white membrane. Of the 24 cases with penile injuries, 1 underwent
conservative treatment, 8 were treated with debridement and suture ligation, and
15 were managed with suture repair of the penis white membrane. During the follow
up period, 62 patients with renal injury had normal renal function. Neither of
the two patients with ureteral injury developed hydronephrosis. Twenty-nine
patients with urethral injury suffered from urethral structure. All patients with
vesical or genital injury recovered. CONCLUSIONS: Urethra and kidney injuries are
the most common acute urogenital system traumas. Superselective arterial
embolization can effectively cease bleeding and maximally protect renal function
and ureterorenoscopic realignment is an easily operative and minimally invasive
technique in the treatment of urethral injuries. As diagnosis and treatment
techniques continue to evolve, minimally invasive procedures should be widely
used in acute urogenital trauma.
PMID- 26430432
TI - Treatment of displaced supracondylar fracture of the humerus in children by open
pining from lateral approach: an investigation of clinical and radiographical
results.
AB - BACKGROUND AND OBJECTIVE: Supracondylar fracture of the humerus is the most
common elbow fracture in children. This fracture needs immediate diagnosis and
treatment, otherwise, it may lead to significant neurovascular and functional
problems. The aim of this study was to assess the short term outcome of displaced
supracondylar fracture of the humerus in children by open reduction and pining
from lateral approach. METHODS: During a period of 15 months from June 2012 to
September 2013, 48 patients (25 boys and 23 girls) less than 10 years old were
enrolled in the study. Inclusion criteria were extension type supracondylar
fractures of humerus, Gaartland type III that closed reduction was unsuccessful
and failed as the initial treatment. The clinical and radiographic results of the
treatment using open reduction and internal fixation by lateral pinning were
evaluated. Outcomes were assessed according to the Flynn's criteria. RESULTS: The
average age of the patients was 6.3 years. The most prevalent range of age was
found about 6-9 years old. All patients had extension type fracture (Gartland
type III). Overall, 47 (98%) patients had closed fracture and only one (2%) had
open fracture. Eighteen patients (37.5%) and 30 patients (62.5%) had involvement
of the dominant and non-dominant extremity respectively. No vascular injury and
infection was seen in patients. One patient (2%) was identified with the radial
nerve injury which, recovered after three months. In the three and six month
follow-up, one patient (2%) was found with the median nerve injury. Since 15
patients were lost to follow-up, the analysis of the clinical and radiographical
results at the end of the 6(th) month were done for 33 patients. According to the
Flynn's criteria, the cosmetic results in 30 out of 33 patients that completed
their follow-up (90.09%) were excellent, in 2 patients (6.1%) were good and one
case (3%) was fair (P=0.051). Also, the functional results in 31 patients (93.9%)
were excellent and in 2 patients (6.1%) were good. Overall, all cases were graded
satisfactory (P=0.047). CONCLUSIONS: Treatment of the supracondylar humeral
fracture in children by open reduction and internal fixation through lateral
pinning is a safe approach with predictable good clinical and radiographical
results.
PMID- 26430433
TI - Cytogenetic and Molecular Analyses of Philadelphia Chromosome Variants in CML
(chronic myeloid leukemia) Patients from Sindh using Karyotyping and RT-PCR.
AB - OBJECTIVE: To determine the frequency of Philadelphia chromosome (Ph) and its
variants in chronic myeloid leukemia (CML) cases at a tertiary care hospital of
Sindh. METHODS: The study was conducted at the Department of Pathology, Liaquat
University of Medical and Health Sciences, Jamshoro and Isra University Hospital,
Hyderabad during May-to-September 2014. Bone marrow and peripheral blood samples
from a total of 145 diagnosed cases of CML were collected. Cytogenetic analyses
were performed using karyotyping as per the International System for Human
Cytogenetic Nomenclature guidelines. All karyotypic images were analyzed using
the Cytovision software. In order to identify BCR-ABL transcripts, RT-PCR was
performed. Statistical analysis of the data was done using SPSS-version-21.0.
RESULTS: Of the 145 samples, a total of 133 (91.7%) were positive for the Ph
(Ph+) while 12 (8.3%) were negative for the Ph (Ph-). Of the 133 Ph+ samples,
standard karyotypes were noted in 121 (91%), simple variants in 9 (6.7%) and
complex variants in 3 (2.3%) of the samples. All the Ph+ samples (n=133) showed
BCR-ABL positivity. Of the 12 Ph- samples, a total of 7 (58.3%) were BCR-ABL
positive and 5 (41.6%) were BCR-ABL-negative. CONCLUSION: Frequency of the Ph was
found to be of 90.9% in CML patients using a highly sensitive technique, the RT
PCR. Cytogenetic abnormalities were at a lower frequency. Cytogenetic and
molecular studies must be conducted for better management of CML cases. These
findings could be very useful in guiding the appropriate therapeutic options for
CML patients.
PMID- 26430434
TI - Is handgrip strength and key pinch measurement related with biochemical
parameters of nutrition in peritoneal dialysis patients?
AB - BACKGROUNDS & OBJECTIVE: End-stage renal disease (ESRD) frequently causes Protein
Energy Wasting (PEW), which is an important morbidity and mortality factor.
Although it is difficult to assess PEW with a reliable method, there are various
methods such as Handgrip strength test (HST), serum albumin, cholesterol, etc.
HST is a simple and reliable antropometric method which is used for nutritional
status and body muscle strength. This study aims to assess the relationship
between HST and biochemical markers in evolution of nutritional status of ESRD
patients. METHODS: This cross-sectional study included 36 consecutive patients,
who are on peritoneal dialysis and 36 healthy -control subjects. Jamar-hand
dynamometer was used for handgrip strength test; a pinch gauge was used for key
pinch. Other antropometric tests included skin fold thicknesses at biceps,
triceps, umbilical, suprailiac and subscapular regions; circumferences at waist
hip, neck and midarm. Biochemical tests were performed only in Peritoneal
Dialysis (PD) group. SPSS for Windows ver. 15.0 was used for statistics. RESULTS:
The mean age of patients was 49.3+/-14.4, and mean age of control group was
43.8+/-10.6 (p=0.075). In PD group dominant hand dynamometer test 1,2 and 3
results were 19.3+/-9.3 kg, 25.3+/-10.8 kg, 25.5+/- 10.6 kg and; 34.2+/-10.3 kg,
34.4+/-9.8 kg, 34.6+/-10.0 kg for control group (p< 0,001). Right key pinch
results were 6.7+/-1.9 kg for patients; 13.5+/-4.5 kg for control group
(p<0.001). Left key pinch results were 6.8+/-1.9 kg for patients; 13.2+/-4.4 kg
for control group (p<0.001). There was not any significant relationship
concerning handgrip or key pinch tests with biochemical parameters. CONCLUSION:
Handgrip Strength Test and key pinch may be reliable, cheap and easily performed
tests for the diagnosis of Protein Energy Wasting in patients on Peritoneal
Dialysis.
PMID- 26430435
TI - Comparing the effectiveness of airway management devices in pre-hospital
emergency care: A randomized clinical trial.
AB - OBJECTIVE: To assess the effectiveness of laryngeal mask airway, endotracheal
tube and oropharyngeal airway for airway management in prehospital emergency
care. METHODS: The study sample of this randomized clinical trial was 54 patients
needing pre-hospital airway management. All cases of intubation (ETI); after two
failed attempts (37 patients), were randomly assigned to the oropharyngeal airway
(OPA), and the laryngeal mask airway (LMA) groups. Patients' hemodynamic, SaO2
and airway management parameters, were compared in three groups. The study data
were analyzed by the Chi-square and one-way ANOVA, Bonferroni post-hoc, using
SPSS, v. 18.0. RESULTS: The results demonstrated that before and after the study,
there was no significant difference among the study groups in terms of
hemodynamic variables (P > 0.05) expect SaO2 (P < 0.001). The results also
revealed that in the ETI group (n=17), the number of attempts and the time spent
on inserting the airway device was significantly more than other two groups (P <
0.05). CONCLUSION: Laryngeal mask airway is as effective as oropharyngial airway
for pre-hospital airway management by paramedics.
PMID- 26430436
TI - Selective lymphadenectomy in endometrial cancer: Retrospective analysis of
morbidity and survival data at a tertiary care centre.
AB - OBJECTIVE: To compare perioperative morbidity and survival data between patients
with early-stage endometrial cancer who did or did not undergo selective
lymphadenectomy. METHODS: Retrospective analysis of 180 patients with early-stage
endometrial carcinoma treated between 1999 and 2008 was performed in Aga Khan
University Hospital, Karachi, Pakistan. RESULTS: Data from 180 patients were
analysed. The selective lymphadenectomy group contained 108 women (60%) and the
no lymphadenectomy group contained 72 women (40%). The median number of lymph
nodes removed was 9. The mean age and extent of disease, as assessed by staging,
tumour size, myometrial invasion, and lymphovascular invasion were comparable
between groups. Upstaging of the disease to stage 3 and 4 occurred in 11% of
patients in the lymphadenectomy group. There were no significant differences in
the medical or surgical complications between groups. At a median follow-up of 26
months, both groups had comparable survival (lymphadenectomy versus no
lymphadenectomy: 34 versus 32 months). Similar survival was noted for patients
who underwent the removal of more or less than 5 pelvic lymph nodes. CONCLUSION:
Selective lymphadenectomy offers the advantage of improved surgical staging but
no therapeutic benefit in terms of overall survival.
PMID- 26430437
TI - Arthroscopic Synovectomy and Postoperative Assisted Radiotherapy for Treating
Diffuse Pigmented Villonodular Synovitis of the Knee: An observational
retrospective study.
AB - OBJECTIVE: This retrospective observational study aims to explore the treatment
procedure and outcomes of arthroscopically assisted radiotherapy for diffuse
pigmented villonodular synovitis (PVNS) of the knee joint. METHODS: From
September 2006 to August 2011, 28 diffuse PVNS patients were diagnosed and
treated under arthroscopy. Twenty six underwent post-operative radiotherapy. All
patients were followed up, and the average follow-up period was 54 months (range:
24 to 72 months). RESULTS: All 26 patients who received external radiotherapy
showed no recurrence at post-operative follow-up; The Lysholm knee joint function
score increased from 54.3+/-9.0 at pre-operation to 71.2+/-6.7 at post-operation
(paired t-test, t = -13.35, P< 0.01). CONCLUSIONS: Arthroscopic synovectomy is an
ideal treatment for PVNS of the knee. Adjuvant post-operative external
radiotherapy prevents the recurrence of diffuse PVNS.
PMID- 26430438
TI - Control of bleeding by silk ligation and diathermy coagulation during
tonsillectomy: A comparison of efficacy of the two techniques in the first 24
hours after surgery.
AB - OBJECTIVE: To assess and compare the relative efficacy of silk ligation and
diathermy coagulation techniques in controlling bleeding during tonsillectomy in
the first 24 hours. METHODS: This prospective study was conducted at the
Department of ENT, Khalifa Gul Nawaz Teaching Hospital, Bannu and this department
related consultants' private clinics from January 1, 2012 to December 31, 2014.
The study included 180 cases. All patients included were having history of
recurrent, acute tonsillitis, with more than 6-7 episodes in one year, five
episodes per year for two years, or three episodes per year for three years. All
the surgeries were performed by dissection method. Haemostasis during the
procedure was secured by either ligation with silk 1 or using diathermy. The
results were analyzed using SPSS 16.0 for windows. RESULTS: A total of180 cases
were included in the study. The ages of the patients ranged from 5 to 40 years
with the mean age of 15.56 years and a std.deviation of +/- 8.24. The male to
female ratio was 1.25:1. The number of hemorrhages occurring was greater in the
'diathermy coagulation' group as compared to the 'silk ligation' group. However,
the observed difference was statistically insignificant (p >.05). CONCLUSION:
Primary haemorrhage occurring during tonsillectomy is a serious threat and
control of bleeding during the procedure should therefore be meticulous. Both
suture ligation and coagulation diathermy for control of bleeders during the
procedure by dissection method are equally effective.
PMID- 26430439
TI - Differences in various biochemical and clinical parameters with respect to family
history of Non Communicable Diseases in fourth year MBBS students of Karachi,
Pakistan.
AB - OBJECTIVE: To observe the differences of various biochemical and clinical
parameters with respect to Family History (FH) of Non-communicable Diseases
(NCDs) in fourth year Bachelor of Medicine, Bachelor of Surgery (MBBS) students.
METHODS: This observational study was conducted at Baqai Institute of Diabetology
& Endocrinology from December 2013 to January 2014. Total 50 medical students
from Dow University of Health Sciences (DUHS) participated in the study.
Statistical Package for Social Sciences (SPSS) version 13 was used to analyze the
data. For cross tabulation and mean comparison z-test and t test were applied.
RESULTS: Out of 50 subjects, there were 26 (52%) females. Mean age of the study
population was 21.56 +/- 0.90 years. Mean serum cholesterol levels with positive
FH of NCDs was significantly higher than negative FH of NCDs (p=0.005). Mean
value of low density lipoprotein (LDL) of positive family history of NCDs was
found higher than those with negative FH (p=0.006) being statistically
significant. The insulin levels in subjects with positive FH of NCDs were higher
than subjects with negative FH of NCDs (p=0.685). However, serum leptin and
plasma renin showed no significant difference with the negative FH of NCDs being
higher compared to positive FH of NCDs (p=0.068) and (p=0.884) respectively.
However, Waist circumference, Body mass index and central obesity in subjects
with positive FH of NCDs shows increasing trend but no statistically significant
difference (p > 0.05) was observed. CONCLUSION: In our study of various
biochemical and clinical parameters with respect to FH of NCDs, Serum Cholesterol
and LDL levels were observed higher and statistically significant.
PMID- 26430440
TI - Bone mineral density and diet of teachers of College of Home Economics at Lahore.
AB - OBJECTIVE: To evaluate the Bone Mineral Density (BMD) and diet of teachers of a
Govt. College of Home Economics in Lahore. METHODS: It was survey research.
Purposive sampling technique was adopted for the selection of 50 teachers from
Govt. College of Home Economics of age group 30 - 60 years. RESULTS: About 46% of
the subjects had BMD ratio in between -2.58 to -4.0 (Osteoporotic category). The
root cause of low BMD ratio was not really age related but in majority of the
sample it was due to sedentary life style and lack of awareness about the
importance of exercise in relation to bone health. CONCLUSION: The total mineral
and vitamin intake required for bone health (calcium, magnesium, phosphorus &
vitamin D) was below the recommended, among majority of the sample.
PMID- 26430441
TI - It is not "Just Circumcision".
AB - OBJECTIVE: Circumcision is one of the most commonly performed operations during
childhood. The procedure is often underestimated in areas where it is frequently
executed due to social and religion-based indications. In fact it might be an
opportunity to detect and to correct any existing penile anomaly. The aim of the
study was to retrospectively evaluate the boys who were admitted to a hospital
for circumcision and the outcome of the procedure. METHODS: The boys who were
brought to outpatient clinics for circumcision between 2009-2015, were
retrospectively evaluated. The indications for hospital admission and the
presence of associated penile anomalies were searched. All the boys were examined
and operated by a single surgeon of the institution. RESULTS: Nine hundred forty
four boys were brought to pediatric surgery outpatient clinics in order to be
circumcised. The operation was performed in 318 of them. The physical examination
revealed penile anomalies in 29 of the 318 cases. The detected anomalies were
webbed penis, penile torsion, hypospadias, chordee without hypospadias and meatal
stenosis. CONCLUSIONS: The proper examination of the boys by a physician prior to
circumcision provides the detection of penile anomalies which can be corrected at
the same session. The arrangements for performing circumcision in hospitals by
the medical staff should be favored. The misleading perception of underestimation
of the procedure where it is ritually performed, should be corrected.
PMID- 26430442
TI - Diagnostic accuracy of ultrasonography in detection of blunt abdominal trauma and
comparison of early and late ultrasonography 24 hours after trauma.
AB - OBJECTIVE: Despite the advantages of ultrasound scan, its use as a screening tool
in blunt abdominal trauma is controversial. The aim of this study was to evaluate
the diagnostic value of early and late ultrasound in patients with blunt
abdominal trauma (BAT). METHODS: In this study which was performed in a level I
trauma center, firstly, 2418 patients with BAT had ultrasound (US) examination by
two trauma expert radiologists. Results were compared with the best available
gold standards such as laparotomy, CT, repeated ultrasound or clinical course
follow-up. Then, 400 patients with BAT were examined by a trained residency
student. RESULTS: In the first phase, sensitivity, specificity, negative
predictive value, positive predictive value and accuracy of ultrasound were 97%,
98.1%, 99.7%, 83% and 98% respectively. In the second phase, they were 97.3%,
97.2%, 97.7%, 96.8% and 97.3% for the early and 98.5%, 97.6%, 98.5%, 97.5% and
98% for the late ultrasound respectively. CONCLUSION: Results obtained from this
study indicate that negative ultrasound findings associated with negative
clinical observation virtually exclude abdominal injury, and confirmation by
performing other tests is unnecessary. High sensitivity and negative predictive
value is achieved if ultrasound is performed by expert trauma radiologist.
PMID- 26430443
TI - Frequency of ABO blood groups and RhD factor in the female population of District
Peshawar.
AB - OBJECTIVE: To determine the frequency of ABO blood group and Rhesus (Rh) D
antigen in the females of "District" Peshawar, Khyber Pakhtunkhwa Province,
Pakistan. METHODS: This cross-sectional study was conducted on 429 women having
pregnancy induced hypertension, admitted in the three teaching hospitals of
Peshawar, over a period of one year. Blood sample was collected from each subject
after taking informed consent. The antigen antibody agglutination slide test for
"blood grouping (ABO)" and RhD factors was done by using IgM and IgG monoclonal
reagents. The antisera used were from Biolaboratory, USA. Data was analyzed for
percentage calculation. RESULTS: The blood group distribution was 134 (31.2%), 43
(10.1%), 116 (27%), 136 (31.7%) for blood groups A, AB, O and B, respectively.
Subjects having blood group B was slightly more dominant, followed by A and O,
while blood group AB was rare in these females. Blood group A Rh negative is more
in female 12 (37.5%) followed by group O 10 (31.3%), group B 09 (28.1%) and group
AB 01 (3.1%). CONCLUSION: Frequency of "Rh-positive blood group" is B, A, O and
AB, whereas the frequency of the most common Rh-negative blood group are A, O, B
and AB respectively. The determination of the frequency of blood groups in the
region would not only help in blood transfusion services, but also reduce the
risk of erythroblastosis foetalis in the neonates.
PMID- 26430445
TI - Significant association of serum creatinine with HbA1C in impaired glucose
tolerant Pakistani subjects.
AB - OBJECTIVE: The present study was conducted to assess the serum concentration of
creatinine and determine its relationship with potential risk factors of diabetes
in Impaired Glucose tolerance subjects. METHODS: This cross sectional study was
conducted on 100 IGT patients who attended Amin Hayat diabetic center in Lahore
from January 2011- June 2011. Patients with age group 34-67 years, (both sexes)
were included in the study. Different demographic parameters as age, BMI, WHR,
B.P, personal history and socioeconomic status were recorded. Oral Glucose
Tolerance Test was performed. The biochemical parameters including HbA1c, lipid
profile, urea, uric acid, creatinine and bilirubin level were measured by
chemistry analyzer. RESULTS: A strong correlation between creatinine and HbA1c
was observed. The level of creatinine was also significantly associated with age
in IGT subjects. Creatinine is non-significantly correlated with Cholesterol, LDL
Chol and TG while negatively significantly associated with BMI, fasting blood
glucose and HDL-Chol. CONCLUSION: The present study concluded significant
association of serum creatinine with HbA1c, BMI and HDL cholesterol.
PMID- 26430444
TI - Outcome of four years experience in laparoscopic ventral hernia repair.
AB - OBJECTIVE: To find out the short term outcomes of laparoscopic ventral hernia
repair (LVHR) during the last four years. METHODS: It was a descriptive and
prospective case series of 53 consecutive patients out of 107 at Department of
General Surgery, Jinnah Post Graduate Medical Center, Unit II, Karachi, from
January 2009 to December 2012. These patients were admitted through out patient
department with complain of lump, pain and discomfort. Most of the patients were
obese. All patients were clinically examined and baseline investigations done.
Fifty three (49.5%) patients underwent laparoscopic repair with mesh placement
and remaining 54 by open surgical repair. RESULTS: Among 53 patients, mean age
was 46 years range (30 - 55). While females were 33(62.2%) and males 20(37.7%).
We observed variety of hernias, in which midline and epigastric hernia were
predominant. The commonest symptom was lump and dragging sensation. The duration
of symptoms ranged between 6 months to one year. About 53 patients (49.5%) had
laparoscopic repair with mesh placement. Average hospital stay was two days. Out
of 53 patients, 4 (7.5%) had cellulitis at trocar site, seroma in 2(3.7%),
2(3.7%) patient complained of persistent pain postoperatively, port site minor
infection was in 2(3.7%) patients, while conversion to open approach was done in
2 (3.7%), postoperative ileus was observed in one (1.8%) patients. CONCLUSIONS:
This study provides the evidence that, laparoscopic repair with mesh placement in
ventral hernia is safe and effective approach compared to open surgical
procedure. It has a low complication rate, less hospital stay and low recurrence.
PMID- 26430446
TI - Success of hydrocone (TORIS-K) soft contact lens for keratoconus and traumatic
keratopathy.
AB - OBJECTIVE: To present success of Toris-K contact lenses in keratoconus and
traumatic keratopathy with irregular corneal surface. METHODS: Toris-K contact
lenses were used to treat 7 eyes of 4 patients with traumatic keratopathy (Case
1) or keratoconus (Case 2, Case 3, and Case 4). All cases had a complete eye
examination before the contact lens application. The case with traumatic
keratopathy was a 32-year-old male who had corneal penetrating injury due to
hobnail strike 23 months ago. The other 3 keratoconus cases were females at the
age of 14, 16 and 22 years old. They had high myopia and irregular astigmatism
due to keratoconus. All patients refused using rigid gas permeable contact lens
because of intolerance. Toris-K contact lenses were fitted on all eyes. All
patients were followed-up for 28 months with a complete ophthalmic examination
and corneal topography every two months. RESULTS: Improvement of BCVA of the
cases was remarkable. All cases were comfortable with their Toris-K contact
lenses for 28 months. There was no significant distortion on the lenses during
follow-up period. CONCLUSION: Toris-K lenses may be an effective alternative
treatment option for the patients with keratoconus and traumatic keratopathy,
especially who cannot tolerate rigid gas permeable contact lenses.
PMID- 26430447
TI - The panacea statistical toolbox of a biomedical peer reviewer.
AB - The main role of a peer reviewer is to make judgments on the research articles by
asking a number of questions to evaluate the quality of the research article.
Statistics is a major part of any biomedical research article, and most reviewers
gain their experiences in manuscript reviewing by undertaking it but not through
an educational process. Therefore, reviewers of the biomedical journals normally
do not have enough knowledge and skills to evaluate the validity of statistical
methods used in biomedical research articles submitted for consideration. Hence,
inappropriate statistical analysis in medical journals can lead to misleading
conclusions and incorrect results. In this paper, the most common basic
statistical guidelines are described that might be a road map to the biomedical
reviewers. It is not meant for statisticians or medical editors who have special
interest and expertise in statistical analysis.
PMID- 26430448
TI - Association of smoking with restenosis and major adverse cardiac events after
coronary stenting: A meta-analysis.
AB - BACKGROUND AND OBJECTIVE: The association between smoking and clinical outcomes
after coronary stenting is controversial. The aim of this meta-analysis was to
assess the association between smoking and in stent restenosis (ISR), major
adverse cardiac events (MACE), or major adverse cardiac and cerebrovascular
events (MACCE) after coronary stenting. METHODS: A search for studies published
before December 2014 was conducted in PubMed, Embase, and Cochrane library. An
inverse random weighted meta-analysis was conducted using logarithm of the odds
ratio (OR) and its standard error for each study. RESULTS: Ten studies
investigated the association between smoking and ISR. Overall, smoking was not
associated with ISR (OR: 1.05, 95% CI: 0.79-1.41; I(2) = 47.8%). Subgroup
analysis also failed to show a significant association between smoking and ISR
risk regardless of bare metal stent (BMS) and drug-eluting stent (DES)
implantation. Eight studies explored the association between smoking and MACE,
but no association was found (OR: 0.92, 95% CI: 0.77-1.10; I(2) = 25.5%), and
subgroup analysis revealed that no distinct difference was found between BMS and
DES implantation. Three studies investigated the association between smoking and
MACCE and significant association was found (OR: 2.09, 95% CI: 1.43-3.06; I(2) =
21.6%). CONCLUSIONS: Our results suggest that in patients undergoing percutaneous
coronary intervention with stent implantation, smoking is not associated with ISR
and MACE; however, smoking is an independent risk factor for MACCE.
PMID- 26430449
TI - Fulminant hepatic failure (FHF) due to acute hepatitis C.
AB - Acute hepatitis C (HCV) infection has been identified as an important cause of
fulminant hepatic failure (FHF), characterized by rapid deterioration of liver
function from massive hepatic necrosis leading to encephalopathy and multi-organ
failure. We admitted a female patient at Shalamar Hospital with jaundice, fever,
encephalopathy and coagulopathy of short duration with no history of any
comorbidity. Her hepatitis viral screen revealed positive anti HCV. Her viral
loads were also high. A diagnosis of FHF due to acute HCV infection was made.
Patient was treated conservatively and improved gradually. In summary, acute HCV
can cause FHF and should be ruled out in patients with FHF of unknown cause in an
endemic country for HCV like Pakistan.
PMID- 26430450
TI - Rare cause of bilateral groin swelling: Round ligament varicosities.
AB - Round ligament varicosity (RLV) is rare and almost all cases are pregnant women.
RLV appears as a unilateral or bilateral groin swelling. Pain and tenderness may
present. Clinical evaluation is inadequate for exact diagnosis because inguinal
hernia has similar findings. Ultrasonography (US) is essential when a groin
swelling is detected in a pregnant woman. We present gray scale US and colour
Doppler US findings of a 32-week pregnant woman with bilateral RLVs at the
inguinal canal, parauterine area and in the myometrium.
PMID- 26430451
TI - Hepatic metastasis complicated by abscess formation.
AB - Hepatic abscesses and hepatic metastasis are common diseases. However, hepatic
abscesses seldom occur in patients with hepatic metastases. We describe a case of
a 67-year-old female patient with abdominal pain in the right upper quadrant.
Magnetic resonance imaging revealed several lesions, with the largest lesion
displaying features of both hepatic pyogenic abscess and liver metastasis. These
features included iso- or hypointense signaling on T1WI and T2WI, hyperintense
signaling on diffusion weighted imaging of the thick wall, and mixed hyperintense
signal in the center on DWI, as well as dramatic and irregular peripheral
enhancement was detected on LAVA dynamic contrast scanning. Aspiration and
culture of the largest lesions revealed Klebsiella pneumoniae and a pathologic
diagnosis of adenocarcinoma. At this point, the patient admitted a history of
colon adenocarcinoma 9 years ago treated with hemicolectomy. Therefore, this
patient was considered to have a hepatic pyogenic abscesses complicated by
hepatic metastasis. The patient began treatment for the responsible pathogens and
underwent chemoembolization of the liver lesions. In special cases, we could
attempt to pursue a more detailed search for coexistence of microorganism
infection and tumor.
PMID- 26430452
TI - Neglected Bilateral Posterior Shoulder Fracture Dislocation in an Uncontrolled
Seizure patient.
AB - Posterior dislocation of the shoulder is a rare injury that occurs secondary to
trauma and seizures. Diagnosis is often missed and treatment is challenging.
Neglected posterior dislocation is associated with Hill-Sachs lesion which leads
to locking of dislocation. Correct diagnosis is achieved by history taking, a
physical examination and appropriate imaging. In neglected shoulder dislocation
with uncontrolled seizure and humeral head defects of up to 45% the McLaughlin
procedure shows excellent results at follow-up.
PMID- 26430453
TI - Chitosan based hydrogels: characteristics and pharmaceutical applications.
AB - Hydrogel scaffolds serve as semi synthetic or synthetic extra cellular matrix to
provide an amenable environment for cellular adherence and cellular remodeling in
three dimensional structures mimicking that of natural cellular environment.
Additionally, hydrogels have the capacity to carry small molecule drugs and/or
proteins, growth factors and other necessary components for cell growth and
differentiation. In the context of drug delivery, hydrogels can be utilized to
localize drugs, increase drugs concentration at the site of action and
consequently reduce off-targeted side effects. The current review aims to
describe and classify hydrogels and their methods of production. The main
highlight is chitosan-based hydrogels as biocompatible and medically relevant
hydrogels for drug delivery.
PMID- 26430455
TI - Minocycline potentiates the anti-hyperalgesic effect of ceftriaxone in CCI
induced neuropathic pain in rats.
AB - Glutamate neurotoxicity and pro-inflammatory cytokines have an important role in
the central sensitization of neuropathic pain. The purpose of the present study
was to evaluate anti-hyperalgesic effect of repeated administration of
ceftriaxone, which selectively activates and increases the expression of
glutamate transporter, as well as minocycline, a selective inhibitor of microglia
activation, either alone or together in Wistar rats subjected to the chronic
constriction injury (CCI) of sciatic nerve. Ceftriaxone (100, 150 and 200 mg/kg)
and minocycline (25, 50 and 100 mg/kg) were administered intraperitoneally from
the day of surgery for seven consecutive days. Thermal hyperalgesia was assessed
by focal radiant heat source on the hind paw of animals one day before surgery
and on 3, 5, 7, 10 and 14 days following that. Ceftriaxone dose dependently,
attenuated thermal hyperalgesia in animals. None of the administered doses of
minocycline affected the CCI induced-thermal hyperalgesia in neuropathic animals.
A fixed dose of minocycline (50 mg/kg) combined with three different doses of
ceftriaxone administered for 7 consecutive days yielded a potentiating effect in
the enhancing latency time to noxious thermal stimulus remaining until the 14th
day post-surgery. The results suggest that modulation of microglia activity could
have a supportive role in the improvement of CCI-induced thermal hyperalgesia and
combination of such classes of drugs which have no antibiotic effects could be a
new and promising therapeutic strategy for treatment.
PMID- 26430454
TI - Formulation and optimization of solid lipid nanoparticle formulation for
pulmonary delivery of budesonide using Taguchi and Box-Behnken design.
AB - Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory
effects. The lungs are an attractive route for non-invasive drug delivery with
advantages for both systemic and local applications. The aim of the present study
was to develop, characterize and optimize a solid lipid nanoparticle system to
deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were
prepared by the emulsification-solvent diffusion method. The impact of various
processing variables including surfactant type and concentration, lipid content
organic and aqueous volume, and sonication time were assessed on the particle
size, zeta potential, entrapment efficiency, loading percent and mean dissolution
time. Taguchi design with 12 formulations along with Box-Behnken design with 17
formulations was developed. The impact of each factor upon the eventual responses
was evaluated, and the optimized formulation was finally selected. The size and
morphology of the prepared nanoparticles were studied using scanning electron
microscope. Based on the optimization made by Design Expert 7((r)) software, a
formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight
ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle
size, zeta potential, entrapment efficiency, loading percent, and mean
dissolution time of adopted formulation were predicted and confirmed to be 218.2
+/- 6.6 nm, -26.7 +/- 1.9 mV, 92.5 +/- 0.52 %, 5.8 +/- 0.3 %, and 10.4 +/- 0.29
h, respectively. Since the preparation and evaluation of the selected formulation
within the laboratory yielded acceptable results with low error percent, the
modeling and optimization was justified. The optimized formulation co-spray dried
with lactose (hybrid microparticles) displayed desirable fine particle fraction,
mass median aerodynamic diameter (MMAD), and geometric standard deviation of
49.5%, 2.06 MUm, and 2.98 MUm; respectively. Our results provide fundamental data
for the application of SLNs in pulmonary delivery system of budesonide.
PMID- 26430456
TI - Molecular expression of adenosine receptors in OVCAR-3, Caov-4 and SKOV-3 human
ovarian cancer cell lines.
AB - Adenosine receptors (A1, A2a, A2b and A3) have several physiological and
pathological roles in cancer cell lines. The present study was carried out to
evaluate the mRNA and protein expression profile and functional role of adenosine
receptors in OVCAR-3, Caov-4 and SKOV-3 ovarian cancer cell lines. The levels of
mRNA and protein expression of A1, A2a, A2b and A3 adenosine receptors in the
ovarian cancer cell lines were measured by Real-time PCR and western blotting.
The functional roles of adenosine receptors were investigated through measurement
of cAMP levels after agonist treatment. The mRNA and protein of all adenosine
receptors subtypes were expressed in the ovarian cancer cell lines. Our findings
demonstrated that A2b and A3 had the most mRNA and protein expression. Moreover,
cAMP assay confirmed the functional role of A2b and A3 adenosine receptors. This
findings demonstrated that A2b and A3 subtypes are most important adenosine
receptors in humn ovarian cancer cell lines. This information provide a strong
possibility into the relationship of A2b and A3 adenosine receptor and ovarian
cancer.
PMID- 26430457
TI - 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene a novel compound
isolated from Pycnocycla spinosa extract with potent anti-spasmodic and
antidiarrheal properties.
AB - Bioassay monitoring of hydroalcoholic extract from the aerial part of Pyconcycla
spinosa revealed that it contains components with spasmolytic activity in vitro.
In addition, P. spinosa extract at oral dose of 1-5 mg/kg inhibits diarrhoea in
animal models. Pharmacological screening of pure compounds isolated from P.
spinosa hydroalcoholic extract led to the identification of 3,7,10,14,15
pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene (PABEM) which is a new diterpene.
In this research, we have investigated antispasmodic and antidiarrheal effects of
PABEM for comparison with P. spinosa extract. Aerial parts of P. spinosa were
extracted with ethanol. For antispasmodic studies, rat isolated ileum was
suspended in Tyrode's solution in an organ bath. The ileum was contracted by
acetylcholine (ACh, 0.5 MUM), serotonin (5-HT, 5 MUM) or electrical field
stimulation (EFS). P. spinosa extract in a concentration dependent manner (10-640
MUg/ml) inhibited ileum contractions induced by ACh, 5-HT or EFS. The new
compound isolated form P. spinosa extract "PABEM" in a similar manner inhibited
the contractile response to ACh, 5-HT and EFS. However, the inhibitory effects of
PABEM were observed at much lower bath concentrations. The relaxation effect of
PABEM was started at 40 ng/ml bath concentration and with 2.5 MUg/ml PABEM in the
bath, the contractile responses of ileum were completely abolished. Both
hydroalcoholic extract of P. spinosa and PABEM reduced intestinal meal transit
and castor oil and MgSO4 induced diarrhoea in mice. However, PABEM was about 10
times more potent than its parent extract. This research shows that PABEM is
probably the main component responsible for antispasmodic and antidiarrheal
actions of P. spinosa extract.
PMID- 26430458
TI - A structural model of the anaphase promoting complex co-activator (Cdh1) and in
silico design of inhibitory compounds.
AB - Anaphase promoting complex (APC) controls cell cycle and chromosome segregation.
The APC activation occurs after binding of co-activators, cdh1 and cdc20. Cdh1
plays a role in cancer pathogenesis and is known as a potential drug target. The
main aim of this study was prediction of 3D structure of cdh1 and designing the
inhibitory compounds based on the structural model. First, 3D structure of cdh1
was predicted by means of homology modelling and molecular dynamics tools,
MODELLER and Gromacs package, respectively. Then, inhibitory compounds were
designed using virtual screening and molecular docking by means AutoDock package.
The overall structure of cdh1 is propeller like and each DW40 repeat contains
four anti-parallel beta-sheets. Moreover, binding pocket of the inhibitory
compounds was determined. The results might be helpful in finding a suitable cdh1
inhibitor for the treatment of cancer.
PMID- 26430459
TI - Evaluation of protective effect of amifostine on dacarbazine induced
genotoxicity.
AB - Anticancer therapy with alkylating agents has been used for many years.
Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with
other chemotherapy drugs. In order to inhibit the formation of secondary cancers
resulting from chemotherapy with DTIC, preventional strategies is necessary. The
present study was undertaken to evaluate the genoprotective effect of amifostine
on the genotoxic effects of DTIC in cell culture condition. To determine the
optimum genotoxic concentration of DTIC, HepG2 cells were incubated with various
DTIC concentrations including 5, 10 and 20 MUg/ml for 2 h and the genotoxic
effects were evaluated by the comet assay. The result of this part of the study
showed that incubation of HepG2 cells with DTIC at 5 MUg/ml was sufficient to
produce genotoxic effect. In order to determine the protective effects of
amifostine on genotoxicity induced by DTIC, HepG2 cells were incubated with
different concentrations of amifostine (2, 3 and 5 mg/ml) for 1 h which was
followed by incubation with DTIC at 5 MUg/ml for 2 h. One hour incubation of
cells with different concentrations of amifostine before incubation with DITC
indicated that at least 5 mg/ml concentration of amifostine can prevent genotoxic
effects induced by DTIC on HepG2 cells under described condition. In conclusion
amifostine could prevent DNA damage induced by DTIC on HepG2 cells.
PMID- 26430460
TI - Optimization of a single-chain antibody fragment overexpression in Escherichia
coli using response surface methodology.
AB - Human epidermal growth factor receptor (HER) family plays an important role in
various types of cancers. As a result, antibodies against HER and the mechanism
of antigen-antibody binding action are under active investigation. We previously
constructed a single-chain variable fragment (ScFv) against HER2, i.e. anti-Her2
ScFv, for expressing in the Escherichia coli. In the present study, we report the
optimization of anti-Her2 ScFv expression in an E. coli host of BL21 (DE3) pLysS
using response surface methodology based on tuning of three cultivation
variables, including isopropyl-beta-D-thiogalactopyranoside (IPTG) concentration,
temperature and post-induction time. A model for protein expression according to
the Box-Behnken design predicted a maximal anti-Her2 ScFv expression at 37
degrees C, a post-induction time of 10.45 h and 0.75 mM IPTG. In addition,
strategies based on inclusion body isolation and affinity chromatography were
applied to purify anti-Her2 ScFv. The purity of the final product for inclusion
bodies isolation and purification by Ni-NTA resin were 70 % and 95 %,
respectively. The solubilization of the inclusion bodies was carried out using
two denaturant agents, guanidine hydrochloride and urea. The present study showed
that guanidine hydrochloride was more effective than urea in solubilizing the
inclusion bodies.
PMID- 26430461
TI - Molecualr Cloning of the capsular antigen F1 of Yersinia pestis in pBAD/gIII
plasmid.
AB - Yersinia pestis which is the causative agent of pneumonic plague and distributed
in all continents has led to many deaths during the history. Because of its high
mortality rate, it must be diagnosed and treated at the earliest time post
infection and therefore, rapid diagnostic tests are required. In the present
study, we cloned the coding sequence of F1 capsular antigen of the bacteria in
the pBAD/gIII plasmid for later expression and purification of the protein to
produce poly and monoclonal antibodies against this antigen, and subsequently to
develop rapid and efficient diagnostics tools for Y. pestis infections.
PMID- 26430462
TI - Essential oil composition of Hypericum triquetrifolium Turra growing wild in
Iran.
AB - The chemical composition of the volatile oil from aerial parts of Hypericum
triquetrifolium Turra was studied by GC-MS. Fifty components (97.1% of the total
composition) were detected in the volatile oil. Germacrene-D (21.7%), beta
caryophyllene (18.3%), delta-cadinene (6.4%), trans-beta-farnesene (4.3%), alpha
humulene (3.8%), beta-selinene (3.7%), gamma-cadinene (3.3%) and trans-phytol
(3.2%) were found to be the major constituents of the oil. The oil of H.
triquetrifolium consisted of five monoterpene hydrocarbons (3.4%), two oxygenated
monoterpenes (0.4%), twenty-two sesquiterpene hydrocarbons (77.1%), eight
oxygenated sesquiterpenes (7.9%) and one oxygenated diterpene (3.2%). Twelve
nonterpenic compounds were also consisted 5.1% of the oil. In conclusion, the oil
of H. triquetrifolium was characterized by a high content of sesquiterpenes
(85.0%), whereas monoterpenes contained only 3.8% of the essential oil.
PMID- 26430463
TI - Vulnerability of Brazilian municipalities to hantavirus infections based on multi
criteria decision analysis.
AB - BACKGROUND: Hantavirus infection is an emerging zoonosis transmitted by wild
rodents. In Brazil, high case-fatality rates among humans infected with
hantavirus are of serious concern to public health authorities. Appropriate
preventive measures partly depend on reliable knowledge about the geographical
distribution of this disease. METHODS: Incidence of hantavirus infections in
Brazil (1993-2013) was analyzed. Epidemiological, socioeconomic, and demographic
indicators were also used to classify cities' vulnerability to disease by means
of multi-criteria decision analysis (MCDA). RESULTS: From 1993 to 2013, 1752
cases of hantavirus were registered in 16 Brazilian states. The highest incidence
of hantavirus was observed in the states of Mato Grosso (0.57/100,000) and Santa
Catarina (0.13/100,000). Based on MCDA analysis, municipalities in the southern,
southeastern, and midwestern regions of Brazil can be classified as highly
vulnerable. Most municipalities in northern and northeastern Brazil were
classified as having low vulnerability to hantavirus cardiopulmonary syndrome.
CONCLUSIONS: Although most human infections by hantavirus registered in Brazil
occurred in the southern region of the country, a greater vulnerability to
hantavirus was found in the Brazilian Midwest. This result reflects the need to
strengthen surveillance where the disease has thus far gone unreported.
PMID- 26430464
TI - iDNA from terrestrial haematophagous leeches as a wildlife surveying and
monitoring tool - prospects, pitfalls and avenues to be developed.
AB - Invertebrate-derived DNA (iDNA) from terrestrial haematophagous leeches has
recently been proposed as a powerful non-invasive tool with which to detect
vertebrate species and thus to survey their populations. However, to date little
attention has been given to whether and how this, or indeed any other iDNA
derived data, can be combined with state-of-the-art analytical tools to estimate
wildlife abundances, population dynamics and distributions. In this review, we
discuss the challenges that face the application of existing analytical methods
such as site-occupancy and spatial capture-recapture (SCR) models to terrestrial
leech iDNA, in particular, possible violations of key assumptions arising from
factors intrinsic to invertebrate parasite biology. Specifically, we review the
advantages and disadvantages of terrestrial leeches as a source of iDNA and
summarize the utility of leeches for presence, occupancy, and spatial capture
recapture models. The main source of uncertainty that attends species detections
derived from leech gut contents is attributable to uncertainty about the spatio
temporal sampling frame, since leeches retain host-blood for months and can move
after feeding. Subsequently, we briefly address how the analytical challenges
associated with leeches may apply to other sources of iDNA. Our review highlights
that despite the considerable potential of leech (and indeed any) iDNA as a new
survey tool, further pilot studies are needed to assess how analytical methods
can overcome or not the potential biases and assumption violations of the new
field of iDNA. Specifically we argue that studies to compare iDNA sampling with
standard survey methods such as camera trapping, and those to improve our
knowledge on leech (and other invertebrate parasite) physiology, taxonomy, and
ecology will be of immense future value.
PMID- 26430466
TI - Training and capacity development: the foundation of interventions to support
young children affected by HIV and AIDS in sub-Saharan Africa.
AB - Many programs to support young children and families affected by HIV and AIDS
depend substantially on a model of cascaded training from international
nongovernmental organizations, through in-country groups and organizations to
services on the ground. In this paper, we describe the training and capacity
building - as described in proposals, progress reports, and individualized
questionnaires - offered by 10 international organizations funded by the Conrad
N. Hilton Foundation to provide supportive services for young children and their
families in five southern and eastern African countries. We related the findings
to effective features of training described in the literature. Training and
capacity development were found to be the most substantial activities in
rendering services to children and families, both in terms of effort and human
and financial resources. A total of 67 trainings were conducted over a period of
18 months. Almost all trainings combine lecture-based instruction, group
work/discussions, and role play, but only half of the trainings report some form
of mentoring, supervision or coaching following the training. Drawing on the
literature, it is likely that more purposeful planning is required in terms of
the selection of trainees, local adaptation and development of materials,
participatory training approaches, and techniques to develop and sustain skills
as well as knowledge. Demonstration and mentorship in the field together with
quality assurance procedures, pre-and post-assessment to evaluate training,
processes to transfer learning into subsequent practice, as well as
certification, are all fundamental steps to ensure that training plays a
supportive role in the behavior changes necessary to support young children
affected by HIV and AIDS and their families.
PMID- 26430467
TI - Does science need bioethicists? Ethics and science collaboration in biomedical
research.
AB - Biomedical research is an increasingly multidisciplinary activity bringing
together a range of different academic fields and forms of expertise to
investigate diseases that are increasingly understood to be complex and
multifactorial. Recently the discipline of ethics has been starting to find a
place in large-scale biomedical collaborations. In this article we draw from our
experience of working with the Malaria Genomic Epidemiology Network (MalariaGEN)
and other research projects to reflect upon the integration of ethics into
biomedical research. We examine the way in which ethics input may be valuable to
research, the forms it tends to take, and also the problems and limitations of
such collaborations.
PMID- 26430465
TI - Does vitamin-D intake during resistance training improve the skeletal muscle
hypertrophic and strength response in young and elderly men? - a randomized
controlled trial.
AB - INTRODUCTION: Recent studies have shown that vitamin-D intake can improve
skeletal muscle function and strength in frail vitamin-D insufficient
individuals. We investigated whether vitamin-D intake can improve the muscular
response to resistance training in healthy young and elderly individuals,
respectively. METHODS: Healthy untrained young (n = 20, age 20-30) and elderly (n
= 20, age 60-75) men were randomized to 16 weeks of daily supplementary intake of
either 48 MUg of vitamin-D + 800 mg calcium (Vitamin-D-group) or 800 mg calcium
(Placebo-group) during a period and at a latitude of low sunlight (December
April, 56 degrees N). During the last 12 weeks of the supplementation the
subjects underwent progressive resistance training of the quadriceps muscle.
Muscle hypertrophy, measured as changes in cross sectional area (CSA), and
isometric strength of the quadriceps were determined. Muscle biopsies were
analyzed for fiber type morphology changes and mRNA expression of vitamin-D
receptor (VDR), cytochrome p450 27B1 (CYP27B1) and Myostatin. RESULTS: In the
vitamin-D groups, serum 25(OH)D concentration increased significantly and at week
12 was significantly different from placebo in both young men (71.6 vs. 50.4
nmol/L, respectively) and elderly men (111.2 vs. 66.7 nmol/L, respectively).
After 12 weeks of resistance training, quadriceps CSA and isometric strength
increased compared to baseline in young (CSA p < 0.0001, strength p = 0.005) and
elderly (CSA p = 0.001, strength p < 0.0001) with no difference between vitamin-D
and placebo groups. Vitamin-D intake and resistance training increased
strength/CSA in elderly compared to young (p = 0.008). In the young vitamin-D
group, the change in fiber type IIa percentage was greater after 12 weeks
training (p = 0.030) and Myostatin mRNA expression lower compared to the placebo
group (p = 0.006). Neither resistance training nor vitamin-D intake changed VDR
mRNA expression. CONCLUSION: No additive effect of vitamin-D intake during 12
weeks of resistance training could be detected on either whole muscle hypertrophy
or muscle strength, but improved muscle quality in elderly and fiber type
morphology in young were observed, indicating an effect of vitamin-D on skeletal
muscle remodeling. TRIAL REGISTRATION: ClinicalTrials with nr. NCT01252381.
PMID- 26430468
TI - Internal displacement and the Syrian crisis: an analysis of trends from 2011
2014.
AB - BACKGROUND: Since the start of the Syrian crisis in 2011, civil unrest and armed
conflict in the country have resulted in a rapidly increasing number of people
displaced both within and outside of Syria. Those displaced face immense
challenges in meeting their basic needs. This study sought to characterize
internal displacement in Syria, including trends in both time and place, and to
provide insights on the association between displacement and selected measures of
household well-being and humanitarian needs. METHODS: This study presents
findings from two complementary methods: a desk review of displaced population
estimates and movements and a needs assessment of 3930 Syrian households affected
by the crisis. The first method, a desk review of displaced population estimates
and movements, provides a retrospective analysis of national trends in
displacement from March 2011 through June 2014. The second method, analysis of
findings from a 2014 needs assessment by displacement status, provides insight
into the displaced population and the association between displacement and
humanitarian needs. RESULTS: Findings indicate that while displacement often
corresponds to conflict levels, such trends were not uniformly observed in
governorate-level analysis. Governorate level IDP estimates do not provide
information on a scale detailed enough to adequately plan humanitarian
assistance. Furthermore, such estimates are often influenced by obstructed access
to certain areas, unsubstantiated reports, and substantial discrepancies in
reporting. Secondary displacement is not consistently reported across sources nor
are additional details about displacement, including whether displaced
individuals originated within the current governorate or outside of the
governorate. More than half (56.4 %) of households reported being displaced more
than once, with a majority displaced for more than one year (73.3 %). Some
differences between displaced and non-displaced population were observed in
residence crowding, food consumption, health access, and education. CONCLUSIONS:
Differences in reported living conditions and key health, nutrition, and
education indicators between displaced and non-displaced populations indicate a
need to better understand migration trends in order to inform planning and
provision of live saving humanitarian assistance.
PMID- 26430469
TI - Erratum to: An interstitial deletion at 8q23.1-q24.12 associated with Langer
Giedion syndrome/ Trichorhinophalangeal syndrome (TRPS) type II and Cornelia de
Lange syndrome 4.
AB - [This corrects the article DOI: 10.1186/s13039-015-0169-9.].
PMID- 26430470
TI - New statistical learning theory paradigms adapted to breast cancer
diagnosis/classification using image and non-image clinical data.
AB - The automated decision paradigms presented in this work address the false
positive (FP) biopsy occurrence in diagnostic mammography. An EP/ES stochastic
hybrid and two kernelized Partial Least Squares (K-PLS) paradigms were
investigated with following studies: methodology performance comparisonsautomated
diagnostic accuracy assessments with two data sets. The findings showed: the new
hybrid produced comparable results more rapidlythe new K-PLS paradigms train and
operate Essentially in real time for the data sets studied. Both advancements are
essential components for eventually achieving the FP reduction goal, while
maintaining acceptable diagnostic sensitivities.
PMID- 26430471
TI - A systematic review and meta-analysis of Harmonic Focus in thyroidectomy compared
to conventional techniques.
AB - INTRODUCTION: Several meta-analyses have been performed comparing the use of a
variety of ultrasonic devices in thyroidectomy to conventional procedures. These
studies have shown the superiority of ultrasonic devices for most outcomes
studied including faster operative time and less blood loss, and equivalent or
better safety for recurrent laryngeal nerve paresis and hypocalcemia. The current
work is the first to examine a single ultrasonic device specifically designed for
thyroid surgery, the Harmonic Focus, in order to confirm its efficacy and safety
in thyroidectomy. METHODS: A comprehensive literature search without language
restrictions was performed for randomized clinical trials comparing Harmonic
Focus and conventional clamp, cut and tie in thyroidectomy. Outcome measures
included operating time, blood loss, post-operative pain, length of hospital
stay, hypocalcemia and recurrent laryngeal nerve paresis. Risk of bias was
analyzed for all studies. Meta-analysis was performed using random effects models
with the inverse-variance method for mean differences of continuous variables and
the Mantel-Haenszel method for risk ratios of dichotomous variables. RESULTS: A
total of 14 studies met the inclusion criteria. Harmonic Focus reduced operative
time by 29 min, a 31 % decrease (p < 0.001), intra-operative blood loss by 45 ml
(p < 0.001), post-operative pain (p < 0.001), length of hospital stay by 0.68
days (p = 0.005), drainage volume by 29 ml (p = 0.01), and occurrence of
transient hypocalcemia by 40 % (p = 0.001). There were no significant differences
between Harmonic Focus and conventional procedures in rate of persistent
hypocalcemia, or rates of transient and persistent recurrent laryngeal nerve
paresis. CONCLUSION: This is the first meta-analysis of Harmonic Focus in thyroid
surgery. In agreement with meta-analyses previously performed on ultrasonic
devices, use of the Harmonic Focus has been shown to be a more effective surgical
procedure compared to conventional methods in thyroidectomy. The low occurrence
of hypocalcemia and recurrent laryngeal nerve paresis confirms that Harmonic
Focus can improve thyroidectomy efficiency without increasing the risk of
complications.
PMID- 26430473
TI - Quality of preventive care before and after prostate cancer diagnosis.
AB - OBJECTIVE: To examine if the use of general preventive services were diminished
in a cohort of men following their diagnosis of prostate cancer. PATIENTS AND
METHODS: 16,604 men enrolled in Kaiser Permanente Southern California who were
newly diagnosed with prostate cancer from January 1, 2002 through December 31,
2009 were passively followed through electronic medical records to determine the
use of preventive services, including screening for colorectal cancer
(colonoscopy and/or fecal occult blood tests (FOBT)), tests for diabetes (glucose
and hemoglobin A1c) and heart disease (serum cholesterol, high density
lipoprotein (HDL) and triglycerides) and vaccinations (influenza and
pneumococcal). Preventive service use was compared in the two years prior to and
following prostate cancer diagnosis using matched odds ratios (MOR) and 95%
confidence intervals (CI) in 2013. RESULTS: Men were more likely to receive a flu
vaccine (MOR: 2.70, 95% CI: 2.52-2.90), lipid tests (MOR: 1.51, 95% CI: 1.42
1.61), diabetes tests (MOR: 2.13, 95% CI: 2.00-2.26) and screening for colorectal
cancer (MOR: 1.80, 95% CI: 1.71-1.89) in the two years after prostate cancer
diagnosis compared to before. Men with advanced disease at diagnosis were more
likely to receive all types of preventive services after diagnosis when compared
to men with localized disease. CONCLUSIONS: Once diagnosed with prostate cancer
in this setting, no less attention was paid to general preventive care, although
there remains room for improvement in pneumococcal vaccination and colon cancer
screening rates. The delivery of high-quality continuing care after diagnosis is
critical for aging cancer patients.
PMID- 26430472
TI - Histone modifications rather than the novel regional centromeres of Zymoseptoria
tritici distinguish core and accessory chromosomes.
AB - BACKGROUND: Supernumerary chromosomes have been found in many organisms. In
fungi, these "accessory" or "dispensable" chromosomes are present at different
frequencies in populations and are usually characterized by higher repetitive DNA
content and lower gene density when compared to the core chromosomes. In the
reference strain of the wheat pathogen, Zymoseptoria tritici, eight discrete
accessory chromosomes have been found. So far, no functional role has been
assigned to these chromosomes; however, they have existed as separate entities in
the karyotypes of Zymoseptoria species over evolutionary time. In this study, we
addressed what-if anything-distinguishes the chromatin of accessory chromosomes
from core chromosomes. We used chromatin immunoprecipitation combined with high
throughput sequencing ("ChIP-seq") of DNA associated with the centromere-specific
histone H3, CENP-A (CenH3), to identify centromeric DNA, and ChIP-seq with
antibodies against dimethylated H3K4, trimethylated H3K9 and trimethylated H3K27
to determine the relative distribution and proportion of euchromatin, obligate
and facultative heterochromatin, respectively. RESULTS: Centromeres of the eight
accessory chromosomes have the same sequence composition and structure as
centromeres of the 13 core chromosomes and they are of similar length. Unlike
those of most other fungi, Z. tritici centromeres are not composed entirely of
repetitive DNA; some centromeres contain only unique DNA sequences, and bona fide
expressed genes are located in regions enriched with CenH3. By fluorescence
microscopy, we showed that centromeres of Z. tritici do not cluster into a single
chromocenter during interphase. We found dramatically higher enrichment of
H3K9me3 and H3K27me3 on the accessory chromosomes, consistent with the twofold
higher proportion of repetitive DNA and poorly transcribed genes. In contrast, no
single histone modification tested here correlated with the distribution of
centromeric nucleosomes. CONCLUSIONS: All centromeres are similar in length and
composed of a mixture of unique and repeat DNA, and most contain actively
transcribed genes. Centromeres, subtelomeric regions or telomere repeat length
cannot account for the differences in transfer fidelity between core and
accessory chromosomes, but accessory chromosomes are greatly enriched in
nucleosomes with H3K27 trimethylation. Genes on accessory chromosomes appear to
be silenced by trimethylation of H3K9 and H3K27.
PMID- 26430474
TI - Transactional Sex: Supply and Demand Among European Men Who have Sex with Men
(MSM) in the Context of Local Laws.
AB - Objectives: Transactional sex (TS) is generally defined as the trading of sex for
material goods. Cast within the broader context of prostitution laws, we examined
variations in the sociodemographic profile of men who have sex with men engaging
in TS by payment direction (buying/selling). Methods: The data were collected as
part of the 38-country European Men who have sex with men Internet Survey
project, conducted in 2010. Results: About 12% of respondents reported engaging
in TS in the past year. TS was associated with laws, age, education, employment,
and residence. Conclusions: The striking sociodemographic differences in TS by
payment direction suggest a power differential and a leading role of
socioeconomic factors in TS.
PMID- 26430475
TI - Epidemiology of Helicobacter pylori infection in dyspeptic Ghanaian patients.
AB - INTRODUCTION: Helicobacter pylori is a gram-negative urease-producing bacterium
causally linked with gastritis, peptic ulcer disease and gastric adenocarcinoma.
Infection is more frequent and acquired at an earlier age in developing countries
compared to European populations. The incidence of Helicobacter pylori infection
in dyspeptic Ghanaian patients was 75.4%. However, epidemiological factors
associated with infection vary across populations. METHODS: This study used a
cross-sectional design to consecutively sample dyspeptic patients at the
Endoscopy Unit of the Korle-Bu Teaching Hospital, Accra between 2010 and 2012.
The study questionnaire elicited their epidemiological clinical characteristics.
Helicobacter pylori infection was confirmed by rapid-urease examination of antral
biopsies at upper Gastro-intestinal endoscopy. RESULTS: The sample population of
dyspeptic patients attending the Endoscopy Unit for upper GI endoscopy yielded
242 patients of which 47.5% were females. The age distribution of H. pylori
infection was even across most age - groups, ranging from 69.2% (61 - 70) years
to 80% (21 - 30) years. Helicobacter pylori prevalence decreased across areas
mapping to the three residential classes in accordance with increasing affluence
with rural areas having the highest prevalence. The unemployed and patients in
farming had relatively high Helicobacter pylori infection rates of 92.3% and
91.7% respectively. CONCLUSION: Helicobacter pylori is endemic in Ghana but the
persistently high prevalence across age groups despite significant community anti
microbial use suggests likely recrudescence or re-infection from multiple sources
in a developing country. Socio-cultural factors such as residential class and
farming may be facilitating factors for its continued prevalence.
PMID- 26430476
TI - [Auricular zona complicated by an invalidating vestibular syndrome].
PMID- 26430478
TI - [Systemic lupus erythematosus induced by isoniazid: a rare complication to fear].
PMID- 26430477
TI - [Oncoplastie with breast conservation in breast cancer treatment: about 16
cases].
PMID- 26430479
TI - Age and sex prevalence of infectious dermatoses among primary school children in
a rural South-Eastern Nigerian community.
AB - INTRODUCTION: Various dermatoses, due to their morbidity characteristics, have
been shown to negatively impact on learning. The most epidemiologically important
seem to be the infectious types because of their transmissibility and amenability
to simple school-health measures. The aim of this study was to assess the
prevalence and sex/age correlates of infectious dermatoses in a rural South
eastern Nigerian community. METHODS: The pupils were proportionately recruited
from the three primary schools based on school population. Stratified simple
random sampling method was adopted and a table of random numbers was used to
select required pupils from each arm. Clinical and laboratory examination was
done to establish diagnoses of infectious skin disease. Data collected were
analyzed using SPSS version 16. RESULTS: The 400 pupils consisted of 153 males
and 247 females. Age range was between 6 and 12 years. The prevalence of
infectious dermatoses was 72.3%. The five most prevalent clinical forms of
infectious dermatoses, in order of decreasing prevalence, were tinea capitis
(35.2%), scabies (10.5%), tinea corporis (5.8%), tinea pedis (5.5%), and impetigo
(5.0%). More cases, generally, occurred among males than females (80.4% vs
67.2%)); while some specific clinical types, pediculosis and seborrheic
dermatitis, exhibited predilection for females. Pyodermas and scabies were
significantly more prevalent in the 7-9 age-group; while tinea capitis, tinea
corporis, seborrheic dermatitis and pediculosis were more associated with >=10
age-group. CONCLUSION: Infectious dermatoses were highly prevalent in the
surveyed population. Many of the clinical types exhibited sex- and age
specificity.
PMID- 26430480
TI - [Skin and nasal involvement: do not ignore sarcoidosis].
PMID- 26430481
TI - [Neglected capitellum fracture in an adult: report of a case and review of
literature].
PMID- 26430482
TI - [Gravido-puerperal pancreatitis: report of 6 cases].
PMID- 26430483
TI - Aural foreign body extraction in children: a double-edged sword.
AB - INTRODUCTION: Foreign body insertion into the ear in children is common world
wide. The goal of this work is to describe the procedural complications of aural
foreign body extraction in children. METHODS: A retrospective analysis of records
of children with aural foreign bodies was conducted. Patients' bio data, type of
foreign bodies, referrals, techniques of removal and complications were extracted
from the case files. The foreign bodies were categorized into graspable and non
graspable objects. Patients with complications caused directly by the foreign
body were excluded. RESULTS: There were 136 cases. Eighty-seven (64.0%) were
males while forty-nine (36.0%) were females. Their age range from 5 days to 16
years with 109 (80.2%) aged below 8 years. Eighty-nine (65.4%) and 47 (34.6%)
cases were treated by otolaryngologists and non-otolaryngologists with a
complication rate of 15.7% and 68.1% respectively. One case suffered severe
hearing loss following complicated attempt at removing foreign body in the only
hearing ear. Overall, the complication rate was higher (44.4%) with removal of
non-graspable than (28.6%) with graspable objects. CONCLUSION: Procedural
complication is an ever-present hazard of aural foreign body extraction in
children. Its occurrence can be prevented or largely reduced if health care
givers know their limitation based on their clinical skills and acquaint
themselves with established criteria for referral. As a rule, we suggest that,
foreign body in the only hearing ear and failed attempted first removal should be
considered criteria for otolaryngologic referral.
PMID- 26430484
TI - Hoffa's fat pad tumours like: results of the arthroscopic resection.
AB - We performed a retrospective cohort study to increase awareness in orthopaedic
community of this rare but interesting disease which is often misdiagnosed as
meniscal pathology and to analyze present results of arthroscopic resection in
seven patients. we retrospectively reviewed records from 2008-2012 and identified
7 patients with symptomatic Hoffa's fat pad impingement. The diagnosis was made
by clinical exam, MRI imaging and verified arthroscopically. Of the 7 patients 2
were excluded due to receiving open resection. The remaining five underwent
arthroscopic resection. Lysholm and American knee society scores were obtained
pre and post operative and at final follow up. There was a significant
improvement in their symptoms and function after the surgery at an average follow
up of 14 months. The one poor result was because of paresthesia over the
distribution of the infrapatellar branch of the saphenous nerve after open
resection. tumours like of the fat pad should be treated by arthroscopic
resection because of less residual pain and less complication was found using
arthroscopy. In case of high volume of tumours only open excision can provide
complete excision.
PMID- 26430485
TI - Contribution and performance of female Community-Directed Distributors in the
treatment of onchocerciasis with Ivermectin in Sub-Saharan Africa: a systematic
review.
AB - The African Program for Onchocerciasis Control (APOC) was launched in 1995 with
the main goal being to boost the fight against onchocerciasis in Africa. In 2011,
over 80 million people benefited from this intervention thanks to the
contribution of 268.718 Community-Directed Distributors (CDD). These significant
results obscure the role of women CDD in this fight. Indeed, the insufficient
involvement of female CDD has been identified as a concern by the APOC partners
early in the program. The present study aims to assess the contribution and
performance of women involved in a strategy to control onchocerciasis by
community-directed treatment with ivermectin in sub Saharan Africa. We searched
the following electronic databases from January 1995 to July 2013: Medline,
Embase (Excerpta Medica Database), CINAHL (Cumulative Index to Nursing and Allied
Health Literature), LILAS (Latin American and Caribbean Literature on Health
Sciences), International Bibliography of Social Sciences, Social Services
Abstracts, and Sociological Abstracts. Two research team members independently
conducted data extraction from the final sample of articles by using a pre
established data extraction sheet. The primary outcome was the contribution of
female CDD in the control of onchocerciasis by community-directed treatment with
Ivermectin. Of 25 hits, 7 papers met the inclusion criteria. For the management
of onchocerciasis, female CDDs are elected by the health committee from the
communities they will serve. The significant proportion of those treated (about
61%) were women, although only 24% of CDDs were women. Many community members
reported that women were more committed, persuasive and more patient than men in
the distribution of ivermectin. Some studies have identified underutilization of
female CDD as one reason for the limited effectiveness or, in some cases, pure
failure related to the distribution of Ivermectin interventions in the fight
against onchocerciasis in sub-Saharan Africa. Evidence from this review suggests
that female CDD contribute to the treatment of onchocerciasis with Ivermectin in
sub-Saharan Africa. Large-scale rigorous studies including Randomized controlled
trials (RCTs) are needed to compare Community-Directed intervention involving men
and women CDDs.
PMID- 26430486
TI - Treatment Outcomes of Long-Pulsed Nd: YAG Laser for Two Different Subtypes of
Rosacea.
AB - BACKGROUND: A variety of lasers have been used for the treatment of rosacea.
However, treatment of this condition with long-pulsed neodymium-doped yttrium
aluminium garnet laser has not been reported yet. OBJECTIVE: To assess the
efficacy and safety of long-pulsed neodymium-doped yttrium aluminium garnet laser
in two different subtypes (erythematotelangiectatic and papulopustular) of
rosacea. METHODS: A total of 66 patients were enrolled in the study. All of the
patients were treated with long-pulsed neodymium-doped yttrium aluminium garnet
laser with 3- to 4-week intervals. Rosacea severity score was assessed by using
photographs. Improvement in severity was defined as the percentage reduction in
severity scores from baseline to the end of treatment. Patients were also asked
about their own opinions of improvement at the end of the treatment. Side effects
were also documented. RESULTS: Good to excellent improvement was achieved in up
to 50 percent of the patients in the erythematotelangiectatic and papulopustular
groups. Percent improvement of global severity was significantly greater in the
erythematotelangiectatic patients than in the papulopustular patients. The
majority of patients from both groups noted a significant improvement of the
lesions. Hypopigmented atrophic scars were seen in two patients. CONCLUSION: The
long-pulsed neodymium-doped yttrium aluminium garnet laser is a safe and
effective treatment for vascular and inflammatory lesions of rosacea.
PMID- 26430487
TI - Impact of Guidance Provided by a Multispectral Digital Skin Lesion Analysis
Device Following Dermoscopy on Decisions to Biopsy Atypical Melanocytic Lesions.
AB - OBJECTIVE: To determine how a multispectral digital skin lesion analysis (MSDSLA)
device data affects the biopsy performance of dermatologists and non
dermatologist practitioners following clinical and dermoscopic pigmented lesion
evaluation. DESIGN: MSDSLA employs near infrared light to image and analyze
pigmented skin lesions. MSDSLA generates a "classifier score" based on
morphological disorganization. Using a logistical regression model, 1) a
probability of being melanoma and, 2) a probability of being melanoma, atypical
melanocytic hyperplasia, or a high grade dysplastic nevus is computed.
PARTICIPANTS were shown clinical images of 12 lesions (2 melanomas in situ, 3
invasive melanomas, and 7 low grade DNs). They were asked first if they would
biopsy the lesion based on clinical images, again after observing dermoscopy
images, and once more when presented with MSDSLA probability information.
SETTING: National dermoscopy conference. PARTICIPANTS: Sixty-four healthcare
providers; 30 dermatologists and 34 non-dermatologist practitioners.
MEASUREMENTS: Sensitivity, specificity, diagnostic accuracy, biopsy rates
Results: For the 30 dermatologists, sensitivity was 65 percent after clinical
evaluation (C) and 65% post-dermoscopy (D) but improved to 91% after MSDSLA. For
the 34 non-dermatologist practitioners, sensitivity improved from 66 percent (C)
to 70 percent (D) to 95 percent after MSDSLA. With MSDSLA information,
dermatologist specificity increased from 40 percent (D) to 58 percent while non
dermatologist practitioners specificity increased from 34 percent (D) to 55
percent. Diagnostic accuracy of malignant and benign lesions decreased for both
groups 55 percent (C) to 51 percent (D) for dermatologists and 54 percent (C) to
49 percent (D) for non-dermatologist practitioners. However, diagnostic accuracy
increased to 72 percent for dermatologists and 72 percent for non-dermatologist
practitioners with MSDSLA data. Non-melanoma biopsy percentages by dermatologists
increased from 53 percent (C) to 60 percent (D), but decreased to 42 percent when
provided with MSDSLA data. Similarly, non-dermatologist practitioners' biopsy
percentages of nonmelanomas increased from 55 percent (C) to 66 percent (D) and
decreased to 45 percent with MSDSLA. CONCLUSION: Decisions to biopsy atypical
melanocytic lesions were more sensitive and specific when MSDSLA information was
provided for both dermatologists and nondermatologist practitioners. Both groups
were also less likely to biopsy nonmelanomas after MSDSLA evaluation. The
authors' results suggest providing practitioners with MSDSLA data leads to
improved biopsy accuracy decreasing the number of nonessential biopsies for
nonmelanocytic lesions even after dermoscopic evaluation.
PMID- 26430488
TI - Randomized, Observer-blind, Split-face Compatibility Study with Clindamycin
Phosphate 1.2%/Benzoyl Peroxide 3.75% gel and Facial Foundation Makeup.
AB - BACKGROUND: Cosmetic compatibility in the treatment of acne is an important issue
significantly impacting quality of life, but often overlooked, as dermatologists
commonly recommended avoidance of cosmetic foundations when treating adult female
patients. Fixed combinations of clindamycin/benzoyl peroxide are widely used in
the treatment of acne, but little is known about the impact of their concomitant
use with facial foundation. OBJECTIVE: To assess the compatibility of clindamycin
phosphate 1. 2%/benzoyl peroxide 3. 75% gel with foundation makeup for up to six
hours after application. METHODS: Twenty-nine female subjects applied makeup to
their face after randomly applying clindamycin phosphate 1. 2%/benzoyl peroxide
3. 75% gel to one side of the face. Investigator and subject self- assessment
included facial skin attributes, facial tolerability, and cosmetic compatibility
post-application and at Hour 6; as well as cutaneous tolerability. RESULTS: No
statistical difference was noted between the treated and untreated side of the
face in terms of coverage, blotchiness, appearance, skin tone, or visual
smoothness. Tolerability was excellent, with no erythema, edema, dryness, and
peeling post-makeup application. For both the treated and untreated side, there
was a slight lack of improvement in cosmetic appearance six hours post-makeup
application. CONCLUSION: Clindamycin/benzoyl peroxide 3. 75% gel was shown to
have excellent cosmetic compatibility with facial foundation.
PMID- 26430489
TI - Evaluation of a Topical Anti-inflammatory/Antifungal Combination Cream in Mild-to
moderate Facial Seborrheic Dermatitis: An Intra-subject Controlled Trial
Examining Treated vs. Untreated Skin Utilizing Clinical Features and Erythema
directed Digital Photography.
AB - OBJECTIVE: To evaluate if nonprescription topical agents may provide positive
outcomes in the management of mild-to-moderate facial seborrheic dermatitis by
reducing inflammation and scale production through clinical evaluation and
erythema-directed digital photography. SETTING: Open-label, prospective, not
blinded, intra-patient, controlled, clinical trial (target area). PARTICIPANTS:
Twenty adult subjects affected by mild-to-moderate facial seborrheic dermatitis
were enrolled and instructed to apply the study cream two times daily, initially
on a selected target area only for seven days. If the subject developed visible
improvement, it was advised to extend the application to all facial affected area
for 21 additional days. MEASUREMENT: Efficacy was evaluated by measuring the
grade of erythema (by clinical examination and by erythema-directed digital
photography), desquamation (by clinical examination), and pruritus (by subject
completed visual analog scale). Additionally, at the end of the protocol, a
Physician Global Assessment was carried out. RESULTS: Eighteen subjects completed
the study, whereas two subjects were lost to follow-up for nonadherence and
personal reasons, respectively. Day 7 data from target areas showed a significant
reduction in erythema. At the end of study, a significant improvement was
recorded for erythema, desquamation, and pruritus compared to baseline. Physician
Global Assessment showed improvement in 89 percent of patients, with a complete
response in 56 percent of cases. CONCLUSION: These preliminary results indicate
that the study cream may be a viable nonprescription therapeutic option for
patients affected by facial seborrheic dermatitis able to determine early and
significant improvement. This study also emphasizes the advantages of using an
erythema-directed digital photography system for assisting in a simple, more
accurate erythema severity grading and therapeutic monitoring in patients
affected by seborrheic dermatitis.
PMID- 26430491
TI - Q-Switched Alexandrite Laser-induced Chrysiasis.
AB - BACKGROUND: Chyriasis is an uncommon side effect that occurs in patients who are
receiving prolonged treatment with either intravenous or intramuscular gold as a
distinctive blue-gray pigmentation of light-exposed skin. Laser-induced
chrysiasis is a rarely described phenomenon in individuals who have received
systemic gold and are subsequently treated with a Q-switched laser. PURPOSE: To
describe the characteristics of patients with laser-induced chrysiasis. METHODS:
The authors describe a 60-year-old woman who developed chrysiasis at Q-switched
alexandrite laser treatment sites. They also reviewed the medical literature
using PubMed, searching the terms chrysiasis, gold, and laser-induced. Patient
reports and previous reviews of these subjects were critically assessed and the
salient features are presented. RESULTS: Including the authors' patient, laser
induced chrysiasis has been described in five Caucasian arthritis patients (4
women and 1 man); most of the patients had received more than 8g of systemic gold
therapy during a period of 3 to 13 years. Gold therapy was still occurring or had
been discontinued as long as 26 years prior to laser treatment. All of the
patients immediately developed blue macules at the Q-switched laser treatment
site. Resolution of the dyschromia occurred in a 70-year-old woman after two
treatment sessions with a long-pulsed ruby laser and the authors' patient after a
sequential series of laser sessions using a long-pulsed alexandrite laser,
followed by a nonablative fractional laser and an ablative carbon dioxide laser.
CONCLUSION: Laser-induced chrysiasis has been observed following treatment with Q
switched lasers in patients who are receiving or have previously been treated
with systemic gold. It can occur decades after treatment with gold has been
discontinued. Therefore, inquiry regarding a prior history of treatment with gold
particularly in older patients with arthritis-should be considered prior to
treatment with a Q-switched laser. Also, treatment with a long-pulsed laser
should be entertained in patients with either idiopathic or laser-induced
chrysiasis. (JClinAesthetDermatol. 2015;8(9):48-53.) Chrysiasis is a distinctive
blue-gray pigmentation of light exposed skin occurring in individuals who are
receiving parenteral gold therapy.1 The 755nm Q-switched alexandrite laser is
effective for the treatment of facial lentigines since the melanin granules
absorb a high proportion of the laser energy and other chromophores offer little
competitive absorption.2 The authors describe a woman who developed chrysiasis at
Q-switched alexandrite laser treatment sites and whose dyschromia was
successfully treated with a sequential series of laser sessions using a long
pulsed alexandrite laser, followed by a nonablative fractional laser and an
ablative carbon dioxide laser.
PMID- 26430490
TI - The Tricky Tear Trough: A Review of Topical Cosmeceuticals for Periorbital Skin
Rejuvenation.
AB - There is a growing demand for noninvasive anti-aging products for which the
periorbital region serves as a critical aspect of facial rejuvenation. This
article reviews a multitude of cosmeceutical ingredients that have good
scientific data, specifically for the periorbital region. Topical treatment
options have exponentially grown from extensively studied retinoids, to recently
developed technology, such as growth factors and peptides. With a focus on the
periorbital anatomy, the authors review the mechanisms of action of topical
cosmeceutical ingredients, effectiveness of ingredient penetration through the
stratum corneum, and validity of clinical trials.
PMID- 26430492
TI - Erratum to: 'Draft genome sequence of Bacillus azotoformans MEV2011, a (Co-)
denitrifying strain unable to grow with oxygen'.
AB - [This corrects the article DOI: 10.1186/1944-3277-10-4.].
PMID- 26430494
TI - The Effect of Lipopolysaccharide on Ischemic-Reperfusion Injury of Heart: A
Double Hit Model of Myocardial Ischemia and Endotoxemia.
AB - INTRODUCTION: Myocardial ischemia may coincide and interact with sepsis and
inflammation. Our objective was to examine the effects of bacterial endotoxin on
myocardial functions and cell injury during acute ischemia. METHODS: Rabbits were
pretreated with incremental doses of E. Coli lipopolysaccharide (LPS) or normal
saline. Myocardial ischemia was induced by 50-minute occlusion of left anterior
descending artery. S-TNFaR was additionally used to block the effects LPS.
RESULTS: Ventricular contractility as it was measured by dp/dt during systole
decreased from 2445+/- 1298 to 1422 +/- 944 mm Hg/s, P = .019. Isovolumetric
relaxation time as an index of diastolic function was prolonged from 50+/-18 ms
to 102+/- 64 ms following ischemia. Pretreatment with low concentrations of LPS
(<1 MUg) had no effect on dp/dt, while at higher concentrations it suppressed
both contractility and prolonged IVRT. Cell injury as measured by cardiac
troponin I level increased to 15.1+/- 3.2 ng/dL following ischemia and continued
to rise with higher doses of LPS. While blocking TNFa did not improve the
myocardial contractility after ischemia, it eliminated additional deleterious
effects of LPS. CONCLUSION: Lower doses of LPS had no deleterious effect on
myocardial function, whereas higher doses of this endotoxin cause cardiac
dysfunction and increased extent of injury.
PMID- 26430495
TI - Real Time 3D Echocardiographic Evaluation of Iatrogenic Atrial Septal Defects
After Percutaneous Transvenous Mitral Commissurotomy.
AB - INTRODUCTION: Percutaneous transvenous mitral commissurotomy (PTMC) is a safe and
effective procedure for relief of severe mitral stenosis. PTMC is being done
widely and many transseptal procedures requiring large diameter catheters,
sheaths are becoming popular. The knowledge of iatrogenic atrial septal defect
(iASD) is vital. This study assessed the use of real-time 3D echocardiography
(RT3DE) and incidence of iASD in a cohort of patients undergoing transseptal
catheterization during PTMC. METHODS: One hundred ten patients underwent PTMC.
The reliability and accuracy of RT3DE for iASD detection was determined, RT3DE
was compared with 2D echocardiography (2DE) for iASD occurrence, influencing
variables analyzed and followed up for 1 year. RESULTS: RT3DE is more reliable
and accurate for the study of iASD than 2DE. Color RT3DE detected iASD in 94
(85.5%), with 2DE iASD was detected in 74 (67.3%) (P < .0001).On follow up 85%
had iASD post procedure, 56% at 6 months, 19% at 1 year follow up. The mean iASD
diameter was 5.41 +/- 3.12 mm and area 6.57 +/- 3.81 mm(2). iASD correlated with
patient height, Wilkins score, pre-PTMC LA 'v', and post-PTMC LVEDP. CONCLUSION:
RT3DE imaging is superior in accuracy to traditional 2DE techniques. All the
modes of RT3DE are useful in the assessment of iASD. iASD measured by RT3DE
correlates with several patient, procedural and echocardiographic variables.
PMID- 26430496
TI - Cardiac Rehabilitation Improves the QRS Fragmentation in Patients With ST
Elevation Myocardial Infarction.
AB - INTRODUCTION: We aimed to evaluate the effect of exercise-based cardiac
rehabilitation (CR) on the fragmented QRS (fQRS) in patients with ST elevation
myocardial infarction (STEMI). METHODS: Ninety-seven patients with STEMI
participated CR and 81 patients as a control group were included to the study.
The trained patients were grouped according to the presence and persistence of
QRS fragmentation on the electrocardiogram (ECG) before and after CR. If the
fragmentation was present on the ECG at the beginning of the CR but not on the
ECG at the end of CR; the transient group, if the fQRS persists after CR; the
persistent fQRS group. ECGs obtained from the control group were grouped
according to the presence of a fQRS on ECG. RESULTS: Among the trained patients,
45 (46%) did not have a fQRS before CR, whereas 52 (54%) presented a fQRS before
CR, which was persistent in 35 patients (the persistent fQRS group) and transient
in 17 patients (the transient fQRS group). Among 81 patients included in the
control group, fQRS was persistent in 41 patients. Presence of fQRS on the ECG
was significantly decreased with CR and it is better in trained group than the
control group (P = .034). There were not significant correlations with other
characteristics, except hypertension. CONCLUSION: The existence of the fQRS
decreases after CR in patients with STEMI especially in hypertensive individuals,
which may be related to improved electrical stability in the myocardium as a
predictor of increase in survival and decrease in major cardiac events.
PMID- 26430493
TI - Dynamics in Transcriptomics: Advancements in RNA-seq Time Course and Downstream
Analysis.
AB - Analysis of gene expression has contributed to a plethora of biological and
medical research studies. Microarrays have been intensively used for the
profiling of gene expression during diverse developmental processes, treatments
and diseases. New massively parallel sequencing methods, often named as RNA
sequencing (RNA-seq) are extensively improving our understanding of gene
regulation and signaling networks. Computational methods developed originally for
microarrays analysis can now be optimized and applied to genome-wide studies in
order to have access to a better comprehension of the whole transcriptome. This
review addresses current challenges on RNA-seq analysis and specifically focuses
on new bioinformatics tools developed for time series experiments. Furthermore,
possible improvements in analysis, data integration as well as future
applications of differential expression analysis are discussed.
PMID- 26430497
TI - Biosynthetic Versus Polytetrafluoroethylene Graft in Extra-anatomical Bypass
Surgery of Takayasu Arteritis Patients With Supra-aortic Disease.
AB - INTRODUCTION: To evaluate treatment outcomes of patients diagnosed with Takayasu
arteritis (TA), who underwent extra-anatomical bypass surgery using biosynthetic
grafts. METHODS: This retrospective study included 12 TA patients considered
eligible for surgical revascularization between January 2005 and May 2011 from
two vascular surgical units in Turkey. Control group consisted of 12 peripheral
arterial disease patients who underwent supra-aortic extra-anatomical bypass
surgery using polytetrafluoroethylene (PTFE) graft. Preoperatively, all patients
underwent Doppler ultrasound and arteriography. Patients were examined every 3
months for clinical findings after monthly follow-up during the first 6 months,
first, second and third year controls. Graft patencies were evaluated by Doppler
ultrasound at each visit. RESULTS: The mean age was 38.6 +/- 4.2 years and the
mean follow-up time was 37.9 +/- 6.9 months for the study group. In Biosynthetic
Group, subclavian-subclavian (n = 2), axillo-axillary (n =9) and carotico
subclavian (n = 1) bypass operations were performed. In PTFE group, subclavian
subclavian (n = 3), axillo-axillary (n = 7), subclavian-left ulnar (n = 1),
subclavian-distal brachial (n = 1) bypass operations were performed. Graft
occlusion occurred in four patients in PTFE Group during follow-up period. These
occlusive lesions were treated successfully according to the routine of each
vascular unit. CONCLUSION: We concluded that in inflammatory diseases like TA,
biosynthetic grafts have promising patency, postoperative clinical findings and
lower rates of complications requiring reintervention in mid-term.
PMID- 26430498
TI - Effects of Selenium in the MAPK Signaling Cascade.
AB - INTRODUCTION: This study aimed to discover by which mechanism selenium (Se)
suppresses stimulated platelets stimulation in oxidative stress underlying
diseases. METHODS: Human platelets pretreated with Se and stimulated by Cu(2+)
oxidized low density of lipoprotein (OxLDL) or thrombin before assessment of P
selectin and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK),
phosphorylated Jun N-terminal kinase (p- JNK), and phosphorylated extracellular
signal-regulated kinases (p-ERK1/2). All variables were measured by solid phase
sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Se significantly
decreased Cu(2+)-OxLDL induced P-selectin expression, as well as p38 and JNK
phosphorylation in platelets, but could not significantly reduce ERK1/2
phosphorylation. CONCLUSION: Se suppresses inflamed platelets. This effect maybe
partly mediated by the p38 or c-JNK signaling pathways. These results create
possibility of new co-anti-inflammatory insight for Se in atherosclerosis.
PMID- 26430500
TI - Investigation of the Association Between 584C/T Polymorphism of EL Gene and Risk
of Premature Coronary Artery Disease in Fars Province.
AB - INTRODUCTION: Endothelial lipase (EL) is a protein from the triglyceride lipase
family which plays an important role in high-density lipoprotein (HDL)
metabolism. One of the most frequently studied variants is 584C/T which causes
the amino acid threonine at codon 111 to convert to isoleucine. Many studies have
shown the association of this variant with HDL-C level and CAD disease. METHODS:
The population of this study consists of 140 patients (all males) with
angiographically confirmed coronary artery disease (CAD) and 80 controls.
Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)
was carried out for genotyping of LIPG 584C/T. Data were analyzed using SPSS.
RESULTS: The results of the study indicated that the frequency of T allele was
significantly lower among CAD patients than among controls (0.27 vs 0.36, P =
.004). However, no significant correlation was found between the 584C/T variant
and serum HDL-C level. Multivariate regression analysis confirmed that the T
allele is significantly associated with CAD disregarding the age, hypertension,
hypercholesterolemia, diabetes and HDL-C (OR = 0.494, 95% CI = 0.253- 0.968, P
=.040). CONCLUSION: It was concluded that the T allele was associated with
protection from CAD in Fars province independent of HDL-C level.
PMID- 26430501
TI - The Effect of Pulmonary Valve Replacement (PVR) Surgery on Hemodynamics of
Patients Who Underwent Repair of Tetralogy of Fallot (TOF).
AB - INTRODUCTION: Pulmonary insufficiency (PI) frequently develops in patients who
underwent repair of tetralogy of fallot (TOF). The aim of present study was to
assess the effect of pulmonary valve replacement (PVR) on hemodynamics of
patients who underwent repair of TOF. METHODS: This retrospective cohort carried
out between July 2010 and October 2012 among consecutive PVRs of 19 patients who
underwent TOF surgery. The PVRs was performed using bioprosthetic (n=17) and
mechanical (n=2) valves. Our data was collected during follow up visits within 6
to 12 month after PVR. RESULTS: Our results show that PVR significantly decreased
right ventricular end-diastolic volume (180.89+/-13.78 vs. 107.21+/-12.02
ml/m(2), P < .01), right ventricular end-systolic volume (105.42+/-15.98 vs.
58.15+/-11.67 ml/m(2), P < .01), RV mass (47.78+/-6.20 vs. 30.68+/-8.95 g/m(2), P
< .01), and PI (48.21+/-1.43% vs. 12.68+/-5.60%, P < .01). Moreover, left
ventricular end-diastolic volume significantly increased (78.05+/-17.21 vs.
90.78+/-14.82 ml/m(2), P < .01) after PVR. The other hemodynamics indexes did not
change, significantly. CONCLUSION: Despite the controversies about efficacy of
PVR after repair of TOF, the remarkable improvement of hemodynamic is a
supportive rationale for performing PVR surgery in TOF patients.
PMID- 26430499
TI - Correlation of Serum Levels of Vitronectin, Malondialdehyde and Hs- CRP With
Disease Severity in Coronary Artery Disease.
AB - INTRODUCTION: Vitronectin (VN), malondialdehyde (MDA) and high-sensitivity C
reactive rotein (hs-CRP) are cooperative agents involved in the atherosclerosis
process. The study was conducted to assess the correlation of VN, MDA and hs-CRP
with the severity of coronary artery disease (CAD). METHODS: Parameters such as
serum VN, MDA and hs-CRP were measured in 250 subjects including 200 patients
with angiographically diagnosed CAD (50 subjects with non-significant CAD, 50
with single vessel disease, 50 with double vessel disease, and 50 with triple
vessel disease) and 50 CAD-free subjects as a control group. Serum VN was
measured with ELISA; MDA was measured based on reaction with thiobarbituric acid
(TBA); and hs-CRP level was measured by a Commercial Kit by Immunoturbidimetry.
RESULTS: Serum VN, MDA and hs-CRP were significantly higher in patient groups
compared to control group (P < .05). The mean value of MDA between 1 vessel and 3
vessel groups had significant difference (P = .01), also mean value of MDA
between 2 vessel and control group and normal group showed significant difference
(P < .001). The difference of MDA between 3 vessel and normal and 1 vessel and
control group was significant (P < .001). CONCLUSION: The association and
correlation between VN, MDA and hs-CRP indicate their involvement in the
atherosclerosis process that may lead to progression of CAD. Also, these findings
suggested that serum levels of VN, MDA and hs-CRP can help as diagnostic and
monitoring markers in CAD patients and as markers of disease severity.
PMID- 26430502
TI - Right Valsalva Sinus Aneurysm Protruding Into the Right Ventricle: A Case Report.
AB - A separation between the aortic media and annulus fibrosus causes a rare cardiac
abnormality called sinus of Valsalva aneurysm (SVA) that may be congenital or
acquired. It is more prevalent in the right coronary sinus (65%-85%) but it has
been seen rarely in non-coronary (10%-30%) or Left coronary sinus (<5%). The most
common complication is rupture of the Aneurysm. We present an 80-year-old male
with expanding right Valsalva sinus aneurysm and protruding into right ventricle.
The conventional treatment is surgical repair under cardio-pulmonary bypass or
percutaneous catheter closure. The aneurysm was successfully excised surgically
under direct guidance of trans-esophageal echocardiography (TEE).
PMID- 26430503
TI - Silent Fistula of the Ascending Aorta to Pericardium by Brucella Endocarditis.
AB - We report the case of a 26-year-old male patient with 2-week history of Brucella
aortic valve endocarditis that was referred from general hospital to our hospital
emergency room with pallor of the skin and mucous membranes accompanied by
systemic hypotension and chest pain. Trans esophageal echocardiography (TEE)
revealed a 30-mm ascending aorta at the pulmonary trunk with no evidence of the
false lumen or intimal flap. TEE also showed a large vegetation of the aortic
valve that limited to noncoronary sinus with moderate pericardial effusion. TEE
did not showed fistula tract of nonaortic coronary sinus ring to intra mural of
aorta and to pericardial cavity. The patient underwent open heart surgery with
resection of destructed aortic valve and vegetation and replacement of aortic
valve with prosthetic valve (Carbomedics, Sorin group. 23 mm sizes) with
separated pledged suture. Debridement of aortic intra mural fistula tract and its
replacement with fresh pericardial patch than performed. The pericardial cavity
had moderate bloody effusion. The patient recovered uneventfully and was
discharged in the 15th postoperative day. In this case, we report a rare silent
clinical presentation of aortic wall fistula by vegetation and aortic ring
abscess and periaortic wall hematoma, and reviewed its medical and surgical
treatment.
PMID- 26430504
TI - Post Cardiopulmonary Bypass Changes in Liver Function: Comment on "J Cardiovasc
Thorac Res 2015;7:49-54".
PMID- 26430505
TI - Cobalt-Catalysed Asymmetric Hydrovinylation of 1,3-Dienes.
AB - In the presence of bidentate 1,n-bis-diphenylphosphinoalkane-CoCl2 complexes
{Cl2Co[P~P]} and Me3Al or methylaluminoxane, acyclic (E)-1,3-dienes react with
ethylene (1 atmosphere) to give excellent yields of hydrovinylation products. The
regioselectivity (1,4- or 1,2-addition) and the alkene configuration (E- or Z-)
of the resulting product depend on the nature of the ligand and temperature at
which the reaction is carried out. Cobalt(II)-complexes of 1,1
diphenylphosphinomethane and similar ligands with narrow bite angles give mostly
1,2-addition, retaining the E-geometry of the original diene. Complexes of most
other ligands at low temperature (-40 degrees C) give almost exclusively a
single branched product, (Z)-3-alkylhexa-1,4-diene, which arises from a 1,4
hydrovinylation reaction. A minor product is the linear adduct, a 5-alkyl-hexa
1,4-diene, also arising from a 1,4-addition of ethylene. As the temperature is
increased, a higher proportion of the major 1,4-adduct appears as the (E)-isomer.
The unexpectedly high selectivity seen in the Co-catalysed reaction as compared
to the corresponding Ni-catalysed reaction can be rationalized by invoking the
intermediacy of an eta4-[(diene)[P~P]CoH]+-complex and its subsequent reactions.
The enhanced reactivity of terminal E-1,3-dienes over the corresponding Z-dienes
can also be explained on the basis of the ease of formation of this eta4-complex
in the former case. The lack of reactivity of the X2Co(dppb) (X = Cl, Br)
complexes in the presence of Zn/ZnI2 makes the Me3Al-mediated reaction different
from the previously reported hydroalkenylation of dienes. Electron-rich
phospholanes, bis-oxazolines and N-heterocyclic carbenes appear to be poor
ligands for the Co(II)-catalysed hydrovinylation of 1,3-dienes. An extensive
survey of chiral ligands reveals that complexes of DIOP, BDDP and Josiphos
ligands are quite effective for these reactions even at -45 degrees C and
enantioselectivities in the range of 90-99 % ee can be realized for a variety of
1,3-dienes. Cobalt(II)-complex of an electron-deficient Josiphos ligand is
especially active, requiring only <1 mol% catalyst to effect the reactions.
PMID- 26430506
TI - High Israeli mortality rates from diabetes and renal failure - Can international
comparison of multiple causes of death reflect differences in choice of
underlying cause?
AB - BACKGROUND: The age-adjusted mortality rate in Israel is low compared to most
Western countries although mortality rates from diabetes and renal failure in
Israel are amongst the highest, while those from cardiovascular diseases (CVD)
are amongst the lowest. This study aims to assess validity of choice of
underlying causes (UC) in Israel by analyzing Israeli and international data on
the prevalence of these diseases as multiple causes of death (MCOD) compared to
UC, and data on comorbidity (MCOD based). METHODS: Age-adjusted death rates were
calculated for UC and MCOD and the corresponding ratio of multiple to underlying
cause of death (SRMU) for available years between 1999 and 2012. Comorbidity was
explored by calculating cause of death association indicators (CDAI) and
frequency of comorbid disease. These results were compared to data from USA,
France, Italy, Australia and the Czech Republic for 2009 or other available year.
RESULTS: Mortality rates for all these diseases except renal failure have
decreased in Israel between 1999 and 2012 as UC and MCOD. In 2009, the SRMU for
diabetes was 2.7, slightly lower than other Western countries (3.0-3.5) showing
more frequent choice as UC. Similar results were found for renal failure. In
contrast, the SRMU for ischemic heart disease (IHD) and cerebrovascular disease
were 2.0 and 2.6, respectively, higher than other countries (1.4-1.6 and 1.7-1.9,
respectively), showing less frequent choice as UC. CDAI data showed a strong
association between heart and cerebrovascular disease, and diabetes in all
countries. In Israel, 40 % of deaths with UC diabetes had IHD and 24 % had
cerebrovascular disease. Renal disease was less strongly associated with IHD.
CONCLUSION: This international comparison suggests that diabetes and renal
failure may be coded more frequently in Israel as UC, sometimes instead of heart
and cerebrovascular disease. Even with some changes in coding, mortality rates
would be high compared to other countries, similar to the comparatively high
diabetes prevalence in Israel at older ages and high rate of end-stage renal
failure. This study highlights the importance of physician training on death
certification practice and need for further progress towards automation in
recording and coding death causes.
PMID- 26430507
TI - Perception of the threat of War in Israel- implications for future preparedness
planning.
AB - BACKGROUND: It has been recently reported that the preparedness of the Israeli
public to a war scenario is mediocre. These findings suggest a need to study the
psychosocial mechanisms behind individual motivation to engage in preparedness
behavior. One component of these mechanisms is the perception of threat. The
purpose of this study is to portray the perception of the threat of war by the
Israeli public and to deduce possible implications for resilience-promoting
policies. METHODS: Portions of the data accumulated in a telephone-based random
sampling of 503 households (representing the Israeli population) performed in
October 2013 were utilized to examine the perception of the threat of war by
Israelis. The questionnaire was used to examine the level of household
preparedness, as well as attitudes toward perception of threat, preparedness
responsibility, willingness to search for information, and sense of preparedness.
Statistical analysis was performed to determine the correlations between
different components of threat perception, and to evaluate the preparedness
promoting features of specific perception factors. RESULTS: The data suggest that
the perception of threat is influenced by different socio-demographic factors. In
particular, age, religion and education seem to play an important role in the
perception of threat. Compared to data collected almost a decade ago, the
likelihood perception and threat intrusiveness rates were significantly reduced.
The regression analysis suggests that perception of the severity of the impact on
a family's routine and willingness to search for information, two known
preparedness promoting factors, can be predicted by various socio-demographic and
threat perception components. CONCLUSION: The data suggest that the Israeli
public, post the Second Lebanon War (2006) and the Gaza conflicts of 2009 and
2012, perceives the probabilities of war and being affected by it as diminished.
The Israeli public demonstrates what can be considered as the unique
characteristics of a war-victimized population. Implications for a future
resilience-promoting policy were discussed.
PMID- 26430508
TI - Policy issues related to educating the future Israeli medical workforce: an
international perspective.
AB - A 2014 external review of medical schools in Israel identified several issues of
importance to the nation's health. This paper focuses on three inter-related
policy-relevant topics: planning the physician and healthcare workforce to meet
the needs of Israel's population in the 21(st) century; enhancing the
coordination and efficiency of medical education across the continuum of
education and training; and the financing of medical education. All three involve
both education and health care delivery. The physician workforce is aging and
will need to be replenished. Several physician specialties have been in short
supply, and some are being addressed through incentive programs. Israel's needs
for primary care clinicians are increasing due to growth and aging of the
population and to the increasing prevalence of chronic conditions at all ages.
Attention to the structure and content of both undergraduate and graduate medical
education and to aligning incentives will be required to address current and
projected workforce shortage areas. Effective workforce planning depends upon
data that can inform the development of appropriate policies and on recognition
of the time lag between developing such policies and seeing the results of their
implementation. The preclinical and clinical phases of Israeli undergraduate
medical education (medical school), the mandatory rotating internship (stage),
and graduate medical education (residency) are conducted as separate "silos" and
not well coordinated. The content of basic science education should be relevant
to clinical medicine and research. It should stimulate inquiry, scholarship, and
lifelong learning. Clinical exposures should begin early and be as hands-on as
possible. Medical students and residents should acquire specific competencies.
With an increasing shift of medical care from hospitals to ambulatory settings,
development of ambulatory teachers and learning environments is increasingly
important. Objectives such as these will require development of new policies.
Undergraduate medical education (UME) in Israel is financed primarily through
universities, and they receive funds through VATAT, an education-related entity.
The integration of basic science and clinical education, development of earlier,
more hands-on clinical experiences, and increased ambulatory and community-based
medical education will demand new funding and operating partnerships between the
universities and the health care delivery system. Additional financing policies
will be needed to ensure the appropriate infrastructure and support for both
educators and learners. If Israel develops collaborations between various
government agencies such as the Ministries of Education, Health, and Finance, the
universities, hospitals, and the sick funds (HMOs), it should be able to address
successfully the challenges of the 21st century for the health professions and
meet its population's needs.
PMID- 26430509
TI - Attainment rate as a surrogate indicator of the intervertebral neutral zone
length in lateral bending: an in vitro proof of concept study.
AB - BACKGROUND: Lumbar segmental instability is often considered to be a cause of
chronic low back pain. However, defining its measurement has been largely limited
to laboratory studies. These have characterised segmental stability as the
intrinsic resistance of spine specimens to initial bending moments by quantifying
the dynamic neutral zone. However these measurements have been impossible to
obtain in vivo without invasive procedures, preventing the assessment of
intervertebral stability in patients. Quantitative fluoroscopy (QF), measures the
initial velocity of the attainment of intervertebral rotational motion in
patients, which may to some extent be representative of the dynamic neutral zone.
This study sought to explore the possible relationship between the dynamic
neutral zone and intervertebral rotational attainment rate as measured with (QF)
in an in vitro preparation. The purpose was to find out if further work into this
concept is worth pursuing. METHOD: This study used passive recumbent QF in a
multi-segmental porcine model. This assessed the intrinsic intervertebral
responses to a minimal coronal plane bending moment as measured with a digital
force guage. Bending moments about each intervertebral joint were calculated and
correlated with the rate at which global motion was attained at each
intervertebral segment in the first 10 degrees of global motion where the
intervertebral joint was rotating. RESULTS: Unlike previous studies of single
segment specimens, a neutral zone was found to exist during lateral bending. The
initial attainment rates for left and right lateral flexion were comparable to
previously published in vivo values for healthy controls. Substantial and highly
significant levels of correlation between initial attainment rate and neutral
zone were found for left (Rho = 0.75, P = 0.0002) and combined left-right bending
(Rho = 0.72, P = 0.0001) and moderate ones for right alone (Rho = 0.55, P =
0.0012). CONCLUSIONS: This study found good correlation between the initial
intervertebral attainment rate and the dynamic neutral zone, thereby opening the
possibility to detect segmental instability from clinical studies. However the
results must be treated with caution. Further studies with multiple specimens and
adding sagittal plane motion are warranted.
PMID- 26430510
TI - Culture and detection of primary cilia in endothelial cell models.
AB - BACKGROUND: The primary cilium is a sensor of blood-induced forces in endothelial
cells (ECs). Studies that have examined EC primary cilia have reported a wide
range of cilia incidence (percentage of ciliated cells). We hypothesise that this
variation is due to the diversity in culture conditions in which the cells are
grown. We studied two EC types: human umbilical vein endothelial cells (HUVECs)
and human microvascular endothelial cells (HMEC-1s). Both cell types were grown
in media containing foetal bovine serum (FBS) at high (20 % FBS and 10 % FBS for
HUVECs and HMEC-1s, respectively) or low (2 % FBS) concentrations. Cells were
then either fixed at confluence, serum-starved or grown post-confluence for 5
days in corresponding expansion media (cobblestone treatment). For each culture
condition, we quantified cilia incidence and length. RESULTS: HUVEC ciliogenesis
is dependent on serum concentration during the growth phase; low serum (2 % FBS)
HUVECs were not ciliated, whereas high serum (20 % FBS) confluent HUVECs have a
cilia incidence of 2.1 +/- 2.2 % (median +/- interquartile range). We report, for
the first time, the presence of cilia in the HMEC-1 cell type. HMEC-1s have
between 2.2 and 3.5 times greater cilia incidence than HUVECs (p < 0.001). HMEC
1s also have shorter cilia compared to HUVECs (3.0 +/- 1.0 MUm versus 5.1 +/- 2.4
MUm, at confluence, p = 0.003). CONCLUSIONS: We demonstrate that FBS plays a role
in determining the prevalence of cilia in HUVECs. In doing so, we highlight the
importance of considering a commonly varied parameter (% FBS), in the
experimental design. We recommend that future studies examining large blood
vessel EC primary cilia use confluent HUVECs grown in high serum medium, as we
found these cells to have a higher cilia incidence than low serum media HUVECs.
For studies interested in microvasculature EC primary cilia, we recommend using
cobblestone HMEC-1s grown in high serum medium, as these cells have a 19.5 +/-
6.2 % cilia incidence.
PMID- 26430512
TI - Mesenchymal stromal cells support endothelial cell interactions in an
intramuscular islet transplantation model.
AB - BACKGROUND: Mesenchymal stromal cells (MSC) have been under investigation for a
number of therapies and have lately been in focus as immunosuppressive actors in
the field of transplantation. Herein we have extended our previously published in
vitro model of MSC-islets in an experimental setting of islet transplantation to
the abdominal muscle. Human islets coated with luciferase-GFP transduced human
MSC were transplanted to the abdomen muscle tissue of NOD-scid ILR2gamma(null)
mice and cellular interactions were investigated by confocal microscopy. RESULTS:
The MSC reduced fibrotic encapsulation and facilitated endothelial cell
interactions. In particular, we show a decreased fraction of alphaSMA expressing
fibrotic tissue surrounding the graft in presence of MSC-islets compared to
islets solely distributed into the muscle tissue. Also, in the presence of MSC,
human islet endothelial cells migrated from the center of the graft out into the
surrounding tissue forming chimeric blood vessels with recipient endothelial
cells. Further, in the graft periphery, MSC were seen interacting with
infiltrating macrophages. CONCLUSIONS: Here, in our experimental in vivo model of
composite human islets and luciferase-GFP-transduced human MSC, we enable the
visualization of close interactions between the MSC and the surrounding tissue.
In this model of transplantation the MSC contribute to reduced fibrosis and
increased islet endothelial cell migration. Furthermore, the MSC interact with
the recipient vasculature and infiltrating macrophages.
PMID- 26430511
TI - Review of the nutritional benefits and risks related to intense sweeteners.
AB - BACKGROUND: The intense sweeteners currently authorised in Europe comprise ten
compounds of various chemical natures. Their overall use has sharply risen in the
last 20 years. These compounds are mainly used to formulate reduced-calorie
products while maintaining sweetness. METHODS: This extensive analysis of the
literature reviews the data currently available on the potential nutritional
benefits and risks related to the consumption of products containing intense
sweeteners. RESULTS AND CONCLUSIONS: Regarding nutritional benefits, the
available studies, while numerous, do not provide proof that the consumption of
artificial sweeteners as sugar substitutes is beneficial in terms of weight
management, blood glucose regulation in diabetic subjects or the incidence of
type 2 diabetes. Regarding nutritional risks (incidence of type 2 diabetes,
habituation to sweetness in adults, cancers, etc.), it is not possible based on
the available data to establish a link between the occurrence of these risks and
the consumption of artificial sweeteners. However, some studies underline the
need to improve knowledge of the links between intense sweeteners consumption and
certain risks.
PMID- 26430513
TI - Foraging behavior links climate variability and reproduction in North Pacific
albatrosses.
AB - BACKGROUND: Climate-driven environmental change in the North Pacific has been
well documented, with marked effects on the habitat and foraging behavior of
marine predators. However, the mechanistic linkages connecting climate-driven
changes in behavior to predator populations are not well understood. We evaluated
the effects of climate-driven environmental variability on the reproductive
success and foraging behavior of Laysan and Black-footed albatrosses breeding in
the Northwest Hawaiian Islands during both brooding and incubating periods. We
assessed foraging trip metrics and reproductive success using data collected from
2002-2012 and 1981-2012, respectively, relative to variability in the location of
the Transition Zone Chlorophyll Front (TZCF, an important foraging region for
albatrosses), sea surface temperature (SST), Multivariate ENSO Index (MEI), and
the North Pacific Gyre Oscillation index (NPGO). RESULTS: Foraging behavior for
both species was influenced by climatic and oceanographic factors. While brooding
chicks, both species traveled farther during La Nina conditions, when NPGO was
high and when the TZCF was farther north (farther from the breeding site). Models
showed that reproductive success for both species showed similar trends,
correlating negatively with conditions observed during La Nina events (low MEI,
high SST, high NPGO, increased distance to TZCF), but models for Laysan
albatrosses explained a higher proportion of the variation. Spatial correlations
of Laysan albatross reproductive success and SST anomalies highlighted strong
negative correlations (>95 %) between habitat use and SST. Higher trip distance
and/or duration during brooding were associated with decreased reproductive
success. CONCLUSIONS: Our findings suggest that during adverse conditions (La
Nina conditions, high NPGO, northward displacement of the TZCF), both Laysan and
Black-footed albatrosses took longer foraging trips and/or traveled farther
during brooding, likely resulting in a lower reproductive success due to
increased energetic costs. Our results link climate variability with both
albatross behavior and reproductive success, information that is critical for
predicting how albatross populations will respond to future climate change.
PMID- 26430514
TI - Systemic lupus erythematosus complicated by diffuse alveolar haemorrhage: risk
factors, therapy and survival.
AB - OBJECTIVES: While diffuse alveolar haemorrhage (DAH) is recognised as a life
threatening complication of systemic lupus erythematosus (SLE), little is known
about its risk factors and response to treatment. We describe 22 cases of DAH in
a US lupus cohort of approximately 1000 patients, and compare them to 66 controls
from the same outpatient cohort. METHODS: We captured variables pertaining to
diagnoses of SLE and secondary antiphospholipid syndrome (APS), and analysed them
by univariate testing. Those variables with p values <0.05 were then further
considered in a multivariate model. Kaplan-Meier curves were constructed for each
group, and survival was analysed by Log-rank test. RESULTS: Of the 22 patients
with DAH, 59% were diagnosed with DAH within 5 years of lupus diagnosis. By
univariate testing, several manifestations of SLE and APS were more common in
patients with DAH, including history of thrombocytopenia, cardiac valve disease,
low C3, leucopenia, neuropsychiatric features, haemolysis, arterial thrombosis,
lupus anticoagulant, secondary APS and low C4. On multivariate analysis, history
of thrombocytopenia and low C3 were maintained as independent risk factors.
Importantly, only two patients had platelet counts <50 000/uL at the time of the
DAH episode, arguing that DAH was not simply a haemorrhagic complication of
thrombocytopenia. All patients were treated with increased immunosuppression,
including various combinations of corticosteroids, plasmapheresis,
cyclophosphamide, rituximab and mycophenolate mofetil. Notably, all patients in
the cohort survived their initial episode of DAH. While the patients with DAH did
well in the short-term, their long-term survival was significantly worse than
controls. Several of the deaths were attributable to thrombotic complications
after recovering from DAH. CONCLUSIONS: To the best of our knowledge, this is the
largest case-control study of lupus DAH to date. History of thrombocytopenia was
strongly predictive of DAH (OR ~40). A number of APS manifestations correlated
with DAH by univariate analysis, and deserve further consideration in larger
studies.
PMID- 26430515
TI - Assessing the extent to which current clinical research is consistent with
patient priorities: a scoping review using a case study in patients on or nearing
dialysis.
AB - PURPOSE OF REVIEW: There is growing acknowledgement that engaging patients to
identify their research priorities is important. Using a case study of patients
on or nearing dialysis, we sought to assess the extent to which recently
completed and ongoing clinical research was consistent with priorities identified
by patients, caregivers, and clinicians. SOURCES OF INFORMATION: Over a 4-year
sampling frame (January 2010 to December 2013), we systematically searched the
medical literature (top 5 nephrology and top 10 general medicine journals
accessed through MEDLINE via Ovid), international randomized controlled trial
(RCT) registries, and national government and kidney research funding
organizations (Canada, U.S., Australia, and U.K.) for published clinical studies,
registered RCTs, and funded clinical studies, respectively. Published clinical
studies, registered RCTs, and funded clinical studies were categorized as to
whether or not they were consistent with the top 10 research priorities
identified by patients, their caregivers, and clinicians in a recent
comprehensive research priority setting exercise. FINDINGS: The search yielded
4293 published articles, 688 RCTs, and 70 funded studies, of which 1116 articles,
315 RCTs, and 70 funded studies were eligible for inclusion. Overall 194
published studies (17.4 %), 71 RCTs (22.5 %), and 15 funded studies (21.4 %)
included topics consistent with the top 10 research priorities identified by
patients. Four of the top 10 research priorities, including strategies to improve
the management of itching, increase access to kidney transplantation, assess the
psychosocial impact of kidney failure, and determine the effects of dietary
restriction received virtually no attention. LIMITATIONS: The top 10 priorities
we used to categorize included studies were identified by Canadian patients,
caregivers, and clinicians. The top research priorities may vary across different
countries. The proportion of published studies that are consistent with the top
10 priorities could be different in nephrology journals with lower impact
factors. Studies related to kidney transplantation and the psychosocial impact of
kidney failure may have been published in journals not included in our search
strategy. IMPLICATIONS: The majority of recently completed or ongoing clinical
studies in patients on or nearing dialysis do not address the top research
priorities of patients, raising concerns that current clinical research may not
be meeting the needs of the ultimate consumer, in this case, patients on or
nearing dialysis. Greater involvement of patients in research is required to
bridge the gap between research and patients' needs.
PMID- 26430516
TI - Thymic Hassall's corpuscles in Nandanam chicken - light and electronmicroscopic
perspective (Gallus domesticus).
AB - The present study was aimed to study the light and electron microscopic studies
of thymic Hassall's corpuscles was done in various age groups of Nandanam Chicken
ranging from day-old to forty weeks. Hassall's corpuscles are special, unique
structures present in thymic medulla and also in the cortex of all the age groups
of Nandanam chicken (from hatch to forty weeks) in the present study. Size of the
Hassall's corpuscles in the medulla is larger than the ones present in the
cortical region of thymus. The Hassall's corpuscles are made up of structureless
eosinophilic mass surrounded by concentrically arranged reticuloepithelial cells.
Under electron microscope, the Hassall's corpuscles were composed of
reticuloepithelial cells interconnected by many desmosomes. The epithelial cells
had abundance of cytoplasmic fibrils and desmosomes with few mitochondria and
ribosomes. The nucleus was oval or round which was slightly indented. The centre
of the Hassall's corpuscles was appeared either solid or cystic. The cystic
corpuscles had cell debris within the cyst lumen.
PMID- 26430517
TI - Project Management of Randomized Clinical Trials: A Narrative Review.
AB - CONTEXT: A well-structured protocol for a clinical trial may be able to answer
clinical questions, but it cannot be deemed enough to ensure success in the face
of incompetent management of time as well as human and economic resources. To
address this problem, in this article, we present our literature review on
evidence as to how a good knowledge of proper management among researchers can
enhance the likelihood of the success of clinical trial projects. EVIDENCE
ACQUISITION: Using multiple search strategies, we conducted a literature review
on published studies in the English language from 2002 to 2012 by searching the
Cochrane Database of Systematic Reviews, MEDLINE, Google Scholar, and EMBASE.
RESULTS: Our review suggests that a successful trial requires a work plan or work
scope as well as a timeline. The trial manager should subsequently manage the
study in accordance with the plan and the timeline. Many research units have
called for a clinical project manager with scientific background and regulatory
skills to effect coordination among various aspects of a clinical trial.
CONCLUSIONS: Project management may benefit both the managerial and scientific
aspects of medical projects and reduce fund waste. However, little has been
written to date on project management in the context of clinical research. The
suggestions represent the views of the individual authors. To provide a high
level of evidence in this regard, we recommend that a randomized controlled trial
be performed to compare trial projects progressed with and without the use of
project management.
PMID- 26430518
TI - Determining Functional Vitamin B12 Deficiency in the Elderly.
AB - BACKGROUND: Elevated concentration of serum total homocysteine usually occurs in
vitamin B-12 deficiency. This metabolite can be measured and used for screening
functional vitamin B-12 deficiency. OBJECTIVES: We assessed functional vitamin
B12 deficiency in Tehranian elderly admitted to elderly research center,
University of Social Welfare and Rehabilitation Sciences. PATIENTS AND MATERIALS:
A cross-sectional study was performed on 232 elderly admitted to elderly research
center in Tehran, Iran in 2012. According to other studies, individuals were
classified into two groups: high risk of vitamin B-12 deficiency (< 220 pmol/L)
and borderline vitamin B-12 (220-258 pmol/L) accompanied by elevated homocysteine
(> 15 micmol/L). RESULTS: Cut-off of 15.0 pmol/L for homocysteine was identified
for persons with normal or elevated concentrations. Among persons aged 65-74 and
>= 75 years, respectively, 56% and 93% were at high risk of vitamin B-12
deficiency. CONCLUSIONS: The prevalence of B12 deficiency was higher in this
study compared to other studies, so more attention and massive efficacious policy
should be designed to reduce the deficiency of this vitamin.
PMID- 26430520
TI - Gastrointestinal Complications of Ferrous Sulfate in Pregnant Women: A Randomized
Double-Blind Placebo-Controlled Trial.
AB - BACKGROUND: Some pregnant women discontinue iron supplements consumption due to
Gastrointestinal (GI) complications, whereas pregnancy induces the same
complications physiologically. OBJECTIVES: The aim of the present study was to
assess GI complications of ferrous sulfate in pregnant women. PATIENTS AND
METHODS: This randomized, double-blind, placebo-controlled clinical trial was
performed on 176 pregnant women referred to prenatal care clinic of Maryam
Hospital from April 2011 to February 2012. Pregnant women with Hb >= 13.2 gr/dL
at 13(th) - 18(th) weeks of gestation were selected based on the inclusion
criteria and were randomly assigned to the ferrous sulfate and placebo groups.
The ferrous sulfate group (n = 90) received a 50-mg ferrous sulfate tablet daily
from the 20(th) week to the end of pregnancy and the placebo group (n = 89)
received one placebo tablet in the same way. All participants were visited twice
at 24(th) - 28(th) and 32(nd) - 36(th) weeks to assess the GI complications as
well as Hb level to determine the Hb changes in two groups. Chi-square test, t
test and Kolmogorov-Smirnov test were used to analyze the data. P value of < 0.05
and confidence level of 95% were considered as statistically significant.
RESULTS: None of the GI complications were significantly different between the
ferrous sulfate and placebo groups at 24(th) - 28(th) and 32(nd) - 36(th) weeks.
Hemoglobin drop lower than 10.5 gr/dL at 24(th) - 28(th) weeks or lower than 11
g/dL at 32(nd) - 36(th) weeks was not observed in any cases. CONCLUSIONS: It can
be concluded that GI complications in pregnant women using ferrous sulfate are
mostly caused by physiologic changes of pregnancy rather than ferrous sulfate;
therefore, it is not reasonable to stop using ferrous sulfate due to GI
complications.
PMID- 26430519
TI - A Safe Method of Tracheal Polyflex Stent Placement: A Review of 20 Patients.
AB - BACKGROUND: Surgery is an appropriate therapeutic approach for tracheal stenosis
due to various benign and malignant conditions. When surgery is postponed for
certain reasons, other options are chosen for airway patency. One alternative is
using airway stents. OBJECTIVES: We aimed to introduce a safe method of tracheal
polyflex stent placement in patients with tracheal stenoses. PATIENTS AND
METHODS: During a 7-year period (2002 - 2008), polyflex stents were used 29 times
among 20 patients for various indications. After encountering many difficulties
in earlier cases, we gradually developed our new method and used it in most of
our patients. In this method, without using large rigid bronchoscopes, the
introducer tube could be used as a bronchoscope with the aid of a zero-degree
lens and ventilating apparatus. In this method, the rate of possible trauma to
the airway can be minimized by avoiding the use of thick rigid bronchoscopies and
the stent can be placed faster and more accurately. RESULTS: Polyflex stents were
used in 11 men (55%) and 9 women with a mean age of 38.5 years. Stents were
removed and changed in 12 cases and replaced with another type of stent in 3
patients. Indications were recurrence of tracheal stenosis (7), multisegmental
tracheal stenosis (3), anesthesia limitations (3), tracheal tumors (2),
dehiscence of tracheal anastomosis (1), severe inflammation of the tracheal
mucosa (1), esophagobronchial fistula (1), and external pressure on the left main
bronchus (1). In one patient, a stent was used to open a kinked Dumon stent as a
temporary life-saving procedure. We found 6 cases of stent migration, 3 cases of
granulation tissue formation, 1 case of infection, and 1 case of surgical site
dehiscence. CONCLUSIONS: Stents would be regarded as a temporary means of
reaching the ideal condition for resection and reconstruction in most patients
with tracheal stenoses. Although an optimal stent has not been introduced yet, we
used polyflex stents in most of our patients with tracheal stenosis due to its
availability and ease of use. We suggest that this method is safe and less time
consuming than its traditional method of placement.
PMID- 26430521
TI - The DSM-5 Levels of Personality Functioning and Severity of Iranian Patients With
Antisocial and Borderline Personality Disorders.
AB - BACKGROUND: Fundamental problems with Personality Disorders (PD) diagnostic
system in the previous version of DSM, led to the revision of DSM. Therefore, a
multidimensional system has been proposed for diagnosis of personality disorder
features in DSM-5. In the dimensional approach of DSM-5, personality disorders
diagnosis is based on levels of personality functioning (Criteria A) and
personality trait domains (Criteria B). OBJECTIVES: The purpose of this study was
firstly, to examine the DSM-5 levels of personality functioning in antisocial and
borderline personality disorders, and second, to explore which levels of
personality functioning in patients with antisocial and borderline personality
disorders can better predicted severity than others. PATIENTS AND METHODS: This
study had a cross sectional design. The participants consisted of 252 individuals
with antisocial (n = 122) and borderline personality disorders (n = 130). They
were recruited from Tehran prisoners, and clinical psychology and psychiatry
centers of Razi and Taleghani Hospitals, Tehran, Iran. The sample was selected
based on judgmental sampling. The SCID-II-PQ, SCID-II and DSM-5 levels of
personality functioning were used to diagnose and assess personality disorders.
The data were analyzed by correlation and multiple regression analysis. All
statistical analyses were performed using the SPSS 16 software. RESULTS: Firstly,
it was found that DSM-5 levels of personality functioning have a strong
correlation with antisocial and borderline personality symptoms, specially
intimacy and self-directedness (P < 0.001). Secondly, the findings showed that
identity, intimacy and self-directedness significantly predicted antisocial
personality disorder severity (P < 0.0001). The results showed that intimacy and
empathy were good predictors of borderline personality disorder severity, as well
(P < 0.0001). CONCLUSIONS: Overall, our findings showed that levels of
personality functioning are a significant predictor of personality disorders
severity. The results partially confirm existing studies.
PMID- 26430522
TI - The Effect of Herbal Tea Containing Fenugreek Seed on the Signs of Breast Milk
Sufficiency in Iranian Girl Infants.
AB - BACKGROUND: One of the important reasons behind termination of breast-feeding in
the first six months after childbirth is insufficient production of breast milk.
OBJECTIVES: The aim of this study was to determine the effect of herbal tea
containing fenugreek seed on the signs of breast milk sufficiency in Iranian girl
infants aged 0 - 4 months, at the medical health centers of Tehran university of
medical sciences. PATIENTS AND METHODS: This study was a clinical trial with a
control group. Seventy-eight girl infants, 0 - 4 months old that were exclusively
breastfed by their mothers, were randomly assigned to the intervention group
(received herbal tea containing 7.5 g fenugreek seed powder in addition to 3 g of
black tea, three times a day) and the control group (received herbal tea
containing 3 g of black tea powder, three times a day). Before and during the
four weeks of study, the signs of breast milk sufficiency were evaluated through
measurement of growth parameters and use of follow-up forms for measuring the
number of wet diapers in one day, frequency of defecation and infant breast
feeding times in a day. RESULTS: Before the intervention there was no significant
difference between weight, height, head circumference, the number of wet diapers
and frequency of defecation between the two groups (P > 0.05), yet the number of
breast feeding times of the control group was more than the Fenugreek group. At
the end of the fourth week in proportion to the pre-intervention conditions, the
weight of the infants in the fenugreek group increased significantly from
5282.0513 +/- 1021.51121 to 6383.0769 +/- 952.06190, while head circumference
increased from 38.3103 +/- 1.62736 to 39.9256 +/- 1.50660, number of wet diapers
from 5.2821 +/- 0.93044 to 8.1648 +/- 1.20620, frequency of defecation from
1.8846 +/- 1.08495 to 2.7326 +/- 0.94771 and the number of breast feeding times
from 9.1795 +/- 1.39778 to 15.9597 +/- 1.45056 (P < 0.001). However, there was no
significant effect on height variation (P = 0.078). While in the control group
there was no significant difference between the mentioned variables (P > 0.05).
CONCLUSIONS: Herbal tea of fenugreek seed in comparison to the control group
improves the signs of breast milk sufficiency.
PMID- 26430523
TI - Child Abuse Reporting Barriers: Iranian Nurses' Experiences.
AB - BACKGROUND: Although in many countries child abuse reporting is mandated, Iranian
nurses report abused cases voluntary. Some of the cases are reported to the
police and others are referred to welfare organizations or other non-governmental
organizations. Absence of a uniform reporting system along with a lack of legal
support in the specific cultural context of Iran has resulted challenges for the
reporters of child abuse. OBJECTIVES: The aim of this study was to explore the
Iranian nurses' experiences of reporting child abuse as well as to explore the
existing barriers. PATIENTS AND METHODS: A qualitative study with conventional
content analysis was conducted to explore the barriers of reporting child abuse.
Individual interviews between 30 and 45 minutes in duration were conducted with a
purposive sample of 16 nurses with direct experience of dealing with children who
had been abused. Graneheim and Lundman's method was used for data analysis.
RESULTS: The data were classified to five themes including "knowledge deficit",
"previous unpleasant experiences about child abuse reporting", "ethical
challenges"," legal challenges" and "cultural beliefs". CONCLUSIONS: According to
the findings, enhancement of nurses and public knowledge about child abuse, legal
issues and jurisprudence along with legislation of clear and simple laws, are
mandatory to protect abused children in Iran.
PMID- 26430524
TI - Heart Surgery Waiting Time: Assessing the Effectiveness of an Action.
AB - BACKGROUND: Waiting time is an index assessing patient satisfaction, managerial
effectiveness and horizontal equity in providing health care. Although heart
surgery centers establishment is attractive for politicians. They are always
faced with the question of to what extent they solve patient's problems.
OBJECTIVES: The objective of this study was to evaluate factors influencing
waiting time in patients of heart surgery centers, and to make recommendations
for health-care policy-makers for reducing waiting time and increasing the
quality of services from this perspective. PATIENTS AND METHODS: This cross
sectional study was performed in 2013. After searching articles on PubMed,
Elsevier, Google Scholar, Ovid, Magiran, IranMedex, and SID, a list of several
criteria, which relate to waiting time, was provided. Afterwards, the data on
waiting time were collected by a researcher-structured checklist from 156
hospitalized patients. The data were analyzed by SPSS 16. The Kolmogorov Smirnov
and Shapiro tests were used for determination of normality. Due to the non-normal
distribution, non-parametric tests, such as Kruskal-Wallis and Mann-Whitney were
chosen for reporting significance. Parametric tests also used reporting medians.
RESULTS: Among the studied variables, just economic status had a significant
relation with waiting time (P = 0.37). Fifty percent of participants had
diabetes, whereas this estimate was 43.58% for high blood pressure. As the cause
of delay, 28.2% of patients reported financial problems, 18.6% personal problem
and 13.5% a delay in providing equipment by the hospital. CONCLUSIONS: It seems
the studied hospital should review its waiting time arrangements and detach them,
as far as possible, from subjective and personal (specialists) decisions. On the
other hand, ministries of health and insurance companies should consider more
financial support. It is also recommend that hospitals should arrange
preoperational psychiatric consultation for increasing patients' emotionally
readiness.
PMID- 26430525
TI - Study of Serum Levels of Leptin, C-Reactive Protein and Nutritional Status in
Hemodialysis Patients.
AB - BACKGROUND: Leptin is secreted by adipose tissue and decreases appetite. However,
the role of leptin in the pathogenesis of hemodialysis (HD)-related malnutrition
has not been fully evaluated. OBJECTIVES: The aim of study was to investigate the
association between the serum leptin levels, serum C-reactive protein (CRP)
levels, and nutritional status in hemodialysis patients. PATIENTS AND METHODS:
This analytical descriptive study included 45 hemodialysis patients and 40
healthy subjects. Biochemical parameters and serum leptin levels were measured.
The nutritional status was evaluated using a food frequency questionnaire (FFQ)
and the calculation of the body mass index (BMI). RESULTS: Serum leptin (P <
0.05) and albumin (P < 0.0001) levels and BMI (P < 0.001) of HD patients were
significantly lower, while CRP levels were significantly higher than those of
controls (P < 0.0001). HD patients consumed the lower daily servings of the food
groups compared to the control subjects (P < 0.0001). A significant positive
correlation between serum levels of leptin and albumin and BMI was demonstrated.
No significant correlations were identified between leptin level, CRP level, and
other variables. CONCLUSIONS: The findings suggest that low levels of leptin may
be a contributory factor for malnutrition in HD patients. Further studies are
required to ascertain the significance of leptin levels in relation to
nutritional factors in hemodialysis patients.
PMID- 26430526
TI - Prevalence of Urinary Tract Infection Among Pregnant Women and its Complications
in Their Newborns During the Birth in the Hospitals of Dezful City, Iran, 2012 -
2013.
AB - BACKGROUND: Urinary tract infection (UTI) is the most common disorder caused by
bacterial agents in pregnancy, which can lead to important complications in
newborn of such mothers in case of inappropriate diagnosis and treatment.
OBJECTIVES: The purpose of this study was to study the prevalence of UTI among
pregnant women and its complications in their newborns during the birth in the
hospitals of Dezful City, Iran, during 2012 - 2013. PATIENTS AND METHODS: In this
cross-sectional retrospective study, 1132 women admitted to Dr. Ganjavian and
Ayatollah Nabavi Hospitals in Dezful City, Iran, during 2012 - 2013 were randomly
allocated into the case and control groups and were matched based on their age,
numbers of pregnancy, sex and diseases of their children. UTI was the only
difference between the two groups. RESULTS: Twenty-two thousand six hundred
deliveries occurred within the course of this study. Due to UTI, 5% of deliveries
led to hospitalization of mothers (1132 patients).Weight and height of newborn
infants of mothers afflicted with UTI (P < 0.001) were significantly lower
compared to newborns of healthy women (P < 0.001). There was a significant
association between the two groups of pregnant women with UTI in terms of type of
delivery (normal and caesarean section) (P < 0.008). CONCLUSIONS: The lower
incidence of UTI in pregnant women compared to other areas of Iran represents the
role of climate and weather in the prevalence of UTI. In addition, the increased
number of low-birth-weight infants had a remarkable correlation with UTI, which
can influence the health of the next generation.
PMID- 26430527
TI - Alpha-Amanitin Poisoning, Nephrotoxicity and Oxidative Stress: An Experimental
Mouse Model.
AB - BACKGROUND: Alpha-amanitin (alpha-AMA) plays a major role in Amanita phalloides
poisoning, showing toxic effects on multi-organs, particularly on the liver and
kidneys. Studies have shown a relationship between alpha-AMA-related injuries and
reactive oxygen species. OBJECTIVES: We aimed to investigate whether there is
renal injury and its relationship with oxidative stress after intraperitoneal
injection of alpha-AMA in mice experimental poisoning models. MATERIALS AND
METHODS: There were 37 male BALB/c laboratory mice treated with alpha-AMA,
according to the study groups: control group (n = 7); low dose (0.2 mg/kg) (n =
10); moderate dose (0.6 mg/kg) (n = 10), and high dose (1 mg/kg) (n = 10). The
sample size was detected according to the ethical committee's decision as well as
similar studies in the literature. After a 48-hour follow-up period, all the
subjects were sacrificed for pathological and biochemical assays. The study was
held in Turkey. RESULTS: alpha-AMA poisoning in mice results in inflammatory
changes and necrosis in renal structures. There were statistically significant
differences between the study groups regarding measured levels of catalase,
superoxide dismutase, glutathione peroxidase, total antioxidant status (TAS),
total oxidant status (TOS) and malonyl dialdehyde in renal homogenates of mice (P
< 0.001, P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.001,
respectively). The TOS and TAS measurements helped to eliminate cumbersome
analysis of diverse oxidant and antioxidant molecules. The TOS levels in renal
homogenate of mice were significantly higher in all the intoxication groups
compared to the control group (5.73, 7.02, 7.77, and 9.65 mmol trolox eq/g
protein and P = 0.002, P = 0.001, and P = 0.001, respectively). The TAS levels in
moderate and high-dose groups were significantly lower than all the other groups
treated with alpha-AMA (0.130, 0.152, 0.065, and 0.087 mmol trolox eq/g protein
and P = 0.031, P = 0.001, and P = 0.001, respectively). CONCLUSIONS: Our results
indicated that alpha-AMA poisoning in mice led to inflammatory changes and
necrosis in renal structures. Biochemical analysis showed a shift in the
oxidative/anti-oxidative balance towards the oxidative status.
PMID- 26430528
TI - Sex Differences in Neuroanatomy of the Human Mirror Neuron System: Impact on
Functional Recovery of Ischemic Hemiparetic Patients.
AB - BACKGROUND: Considering the higher activity of mirror neuron system in females,
they frequently have better performance in empathy, interpersonal sensitivity,
and emotional recognition compared to males. OBJECTIVES: The purpose of this
study was to assess whether gender difference in neuroanatomy of the human mirror
neuron system has any impact on functional recovery of ischemic hemiparetic
patients. PATIENTS AND METHODS: This single-blind clinical trial was conducted on
24 patients with cerebrovascular accident (CVA) in the age range of 45 - 60
years, referring at a rehabilitation center in Tehran, Iran, during 2013 - 2014.
Sampling method was stratified random sampling. The subjects were assigned to 2
groups of 12 males and 12 females. Then, each group was randomly divided into 2
groups (totally 4 groups, n = 6 for each group): women watching functional
movies, control women, men watching functional movies, and control men. Movies
were shown to patients and then, they were evaluated by Timed Up and Go (TUG),
Six-minute walk test (SMW), Barthel index (BI), and Berg balance scale (BBS).
RESULTS: Comparison of all variables related to functional activities of all
groups before and after watching movies revealed significant differences. The
highest percentage of change and improvement was observed in groups 1 and 3
watching the functional movies (P = 0.0001). Percentage of improvement in women
of groups 1 and 2 was higher than men in groups 3 and 4 (P = 0.0003). The changes
in group of females watching the functional movies (group 1) were significantly
greater than in other groups (P < 0.0001). CONCLUSIONS: The Sex differences in
the neuroanatomy of the human mirror neuron system affect functional recovery of
patients with hemiparesis. The improvement in studied women was found to be
significantly greater than studied men. The results indicate a higher chance of
recovery among hemiparetic women, especially those watching functional movies.
PMID- 26430529
TI - Better Hemodynamic Profile of Laryngeal Mask Airway Insertion Compared to
Laryngoscopy and Tracheal Intubation.
AB - BACKGROUND: Laryngoscopy and tracheal intubation can cause serious cardiovascular
responses in patients such as hypertension, tachycardia, and arrhythmias.
Alternative airway maintenance techniques may attenuate these hemodynamic stress
responses. OBJECTIVES: This study aimed to compare the immediate hemodynamic
effects of the insertion of laryngeal mask airway supreme (LMA-S) and classic
(LMA-C) with laryngoscopy and Endotracheal Intubation (ETT). PATIENTS AND
METHODS: This study was a prospective, double-blind, and randomized clinical
trial conducted on 150 patients aged 18 to 50 years with ASA I (American Society
of Anesthesiologists), in the general operating room of Shahid Mohammadi
hospital, Hormozgan university of medical sciences, Bandar Abbas, Iran. In the
ETT group, endotracheal intubation was performed using the Macintosh
laryngoscope; while for the LMA-C and LMA-S groups, LMA Classic and LMA Supreme
were inserted, respectively. The induction and maintenance of anesthesia were
similar in all patients. The hemodynamic parameters such as heart rate (HR),
systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured
before (baseline) and after induction of anesthesia at 4 different time points.
The statistical analysis was done and P value less than 0.05 was considered
significant. RESULTS: Participants in all groups were similar in terms of gender,
age, weight, height, and Mallampati class. The mean +/- SD of SBPs (105.62 +/-
12.12, 112.90 +/- 12.2, and 112.48 +/- 15.14 mm Hg, respectively for ETT, LMA-C,
and LMA-S) and DBPs (64.64 +/- 10.23, 73.78 +/- 9.70, and 71.20 +/- 12.27 mm Hg,
respectively for ETT, LMA-C, and LMA-S) were significantly lower in the ETT group
compared to LMA groups 5 minutes after device insertion (P < 0.01 for SBPs and P
< 0.001 for DBPs); however these values were lower than the baseline values in
all groups. There were no differences in the mean SBP and DBPs between the three
groups at the other time points. The mean +/- SD heart rates in the ETT group,
compared to the LMA-C and LMA-S groups, were considerably higher in the first
minute (100.06 +/- 18.27, 82.50 +/- 10.52, and 82.00 +/- 13.60 bpm, respectively
for ETT, LMA-C, and LMA-S), third minute (91.04 +/- 17.12, 78.84 +/- 11.23, and
78.90 +/- 13.41 bpm, respectively for ETT, LMA-C, and LMA-S) and fifth minute
(85.82 +/- 16.01, 75.78 +/- 11.73, and 75.04 +/- 13.90 bpm, respectively for ETT,
LMA-C, and LMA-S) after intubation (P < 0.001). There were no significant
differences between the LMA-C and LMA-S groups in terms of hemodynamic
parameters. CONCLUSIONS: Maintaining the airway using laryngeal mask airway is
associated with less cardiovascular responses compared to direct laryngoscopy and
tracheal intubation.
PMID- 26430530
TI - Effect of Acupressure on Cervical Ripening.
AB - BACKGROUND: Cervical ripening is one of the main stages of initiation labor.
Acupressure in Chinese medicine is considered as an invasive technique, which
through reliving oxytocin ripens the cervix. Acupoint Sanyinjiao (SP6) was
selected in this study because it is the acupoint selected in gynecology and it
is easy for women to locate and apply pressure without medical assistance.
OBJECTIVES: The aim of this study was to determine the effect of acupressure on
cervical ripening. PATIENTS AND METHODS: In this randomized clinical trial, 150
primigravida with term pregnancy who had referred to Deziani hospital in Gorgan
were chosen and divided to three groups: in the first group acupressure was done
by the researcher while in the second groups this was performed by the mother her
self, and the third group served as a control and only received routine care. For
both intervention groups the pressure was applied on Sp6 for about 20 minutes
during one to five days. Elements were checked from cervical ripening at 48 and
96 hours after intervention and at the time of hospitalization. The tools for
gathering information included demographic characteristics and midwifery history
questionnaire, daily records and follow up forms. Content validity was used for
validity of tools. Reliability of the observation check-list and physical
examination was confirmed by inter-rater scores (inter observer), and daily
records by test-re-test. Data was analyzed by analysis of variance (ANOVA),
Kruskal-Wallis and Chi-squared tests (P <= 0.05). RESULTS: There was a
significant difference between mothers' educations in the three groups. Most of
the mothers (59.5%) in the researcher-performed acupressure group had secondary
education. Cervical ripening was significantly different between the three groups
after 48 hours (P <= 0.05), yet there was no significant difference after 96
hours and at the time of admission. Mean Bishop score was enhanced after 48 hours
in the researcher-performed acupressure group (P <= 0.021) and the self-performed
acupressure group (P <= 0.007) in comparison to the control group. CONCLUSIONS:
The results showed that acupressure is a safe technique and leads to cervical
ripening. Thus, regarding the desired results that were achieved when mothers
applied acupressure themselves, it could be suggested that it is beneficial for
mothers to be trained to apply this method at home.
PMID- 26430531
TI - Embryonal Rhabdomyosarcoma of the Adult's Vocal Cord: A Case Report.
AB - INTRODUCTION: Although embryonal rhabdomyosarcomas (ERMS) represent the most
common (50% - 60%) clinical form of rhabdomyosarcoma, these are extremely rare in
adult's vocal cords. To date, only five cases of laryngeal ERMS have been
reported in adults and only one of them involved the vocal cords. CASE
PRESENTATION: Herein, we reported a case of a 22-year-old woman diagnosed with
ERMS, T1N0M0 stage, localized at the right vocal cord. Tumor was successfully
treated with a radical excision and selective neck dissection and followed-up for
5 years with no evidence of local recurrence. CONCLUSIONS: Immunohistochemistry
combined with computerized tomography (CT) and color Doppler solography of the
neck and thorax should be performed. This study suggested that surgical resection
was suitable for the treatment of this disease and reported the evaluations of an
extremely rare case for five years.
PMID- 26430532
TI - Examination of the Factorial Structure of Adverse Childhood Experiences and
Recommendations for Three Subscale Scores.
AB - OBJECTIVE: The purpose of the current investigation is to assess and validate the
factor structure of the Behavioral Risk Factor Surveillance System's (BRFSS)
Adverse Childhood Experience (ACE) module. METHOD: ACE data available from the
2009 BRFSS survey were fit using exploratory factor analysis (EFA) to estimate an
initial factorial structure. The exploratory solution was then validated using
confirmatory factor analysis (CFA) with data from the 2010 BRFSS survey. Lastly,
ACE factors were tested for measurement invariance using multiple group factor
analysis. RESULTS: EFA results suggested that a 3-factor solution adequately fit
the data. Examination of factor loadings and item content suggested the factors
represented the following construct areas: Household Dysfunction,
Emotional/Physical Abuse, and Sexual Abuse. Subsequent CFA results confirmed the
3-factor solution and provided preliminary support for estimation of an overall
latent ACE score summarizing the responses to all available items. Measurement
invariance was supported across both gender and age. CONCLUSIONS: Results of this
study provides support for the use of the current ACE module scoring algorithm,
which uses the sum of the number of items endorsed to estimate exposure. However,
the results also suggest potential benefits to estimating 3 separate composite
scores to estimate the specific effects of exposure to Household Dysfunction,
Emotional/Physical Abuse, and Sexual Abuse.
PMID- 26430533
TI - Serum procalcitonin is a marker for prediction of readmission from an
intermediate care to an acute care hospital in neurosurgical patients.
AB - BACKGROUND: Readmission of patients to acute hospitals contributes significantly
toward inefficient utilization of healthcare resources, with studies quoting up
to 90% being preventable. We aim to report and analyze the factors involved in
the readmission of neurosurgical patients who had been previously transferred to
an intermediate step-down care facility, and explore possible predictive markers
for such readmissions. METHODS: We conducted a retrospective analysis of all 129
neurosurgical patients who were transferred from out acute tertiary hospital to
an intermediate care facility. The cases were segregated into those who were
readmitted and those who were not readmitted back to our acute center. The
demographic data, clinical features, diagnoses, treatment modalities, pretransfer
laboratory findings, and inpatient complications were compared with readmission
rate. RESULTS: There were 23 patients (17.8%) who were readmitted to our acute
hospital. The most common causes of readmission was infection (n = 12, 52.2%). We
found a statistically significant correlation between the higher pretransfer
procalcitonin levels with the readmission of our patients (P = 0.037). There was
also a significant difference noted between ethnic groups (P = 0.026) and having
no complications of disease or treatment (P = 0.008), with readmission.
CONCLUSION: Procalcitonin is a pro-hormone known to correlate with infection and
poor neurological status. We have found that its serum values correlate
significantly with the readmission rates of neurosurgical patients in our study.
We postulate that by ensuring normality in procalcitonin levels prior to transfer
to an intermediate care facility, potentially half of neurosurgical readmissions
can be prevented.
PMID- 26430534
TI - A conceptual model for translating omic data into clinical action.
AB - Genomic, proteomic, epigenomic, and other "omic" data have the potential to
enable precision medicine, also commonly referred to as personalized medicine.
The volume and complexity of omic data are rapidly overwhelming human cognitive
capacity, requiring innovative approaches to translate such data into patient
care. Here, we outline a conceptual model for the application of omic data in the
clinical context, called "the omic funnel." This model parallels the classic
"Data, Information, Knowledge, Wisdom pyramid" and adds context for how to move
between each successive layer. Its goal is to allow informaticians, researchers,
and clinicians to approach the problem of translating omic data from bench to
bedside, by using discrete steps with clearly defined needs. Such an approach can
facilitate the development of modular and interoperable software that can bring
precision medicine into widespread practice.
PMID- 26430535
TI - Whole slide image with image analysis of atypical bile duct brushing:
Quantitative features predictive of malignancy.
AB - BACKGROUND: Whole slide images (WSIs) involve digitally capturing glass slides
for microscopic computer-based viewing and these are amenable to quantitative
image analysis. Bile duct (BD) brushing can show morphologic features that are
categorized as indeterminate for malignancy. The study aims to evaluate
quantitative morphologic features of atypical categories of BD brushing by WSI
analysis for the identification of criteria predictive of malignancy. MATERIALS
AND METHODS: Over a 3-year period, BD brush specimens with indeterminate
diagnostic categorization (atypical to suspicious) were subjected to WSI
analysis. Ten well-visualized groups with morphologic atypical features were
selected per case and had the quantitative analysis performed for group area,
individual nuclear area, the number of nuclei per group, N: C ratio and nuclear
size differential. RESULTS: There were 28 cases identified with 17 atypical and
11 suspicious. The average nuclear area was 63.7 um(2) for atypical and 80.1
um(2) for suspicious (+difference 16.4 um(2); P = 0.002). The nuclear size
differential was 69.7 um(2) for atypical and 88.4 um(2) for suspicious
(+difference 18.8 um(2); P = 0.009). An average nuclear area >70 um(2) had a 3.2
risk ratio for suspicious categorization. CONCLUSION: The quantitative criteria
findings as measured by image analysis on WSI showed that cases categorized as
suspicious had more nuclear size pleomorphism (+18.8 um(2)) and larger nuclei
(+16.4 um(2)) than those categorized as atypical. WSI with morphologic image
analysis can demonstrate quantitative statistically significant differences
between atypical and suspicious BD brushings and provide objective criteria that
support the diagnosis of carcinoma.
PMID- 26430537
TI - Validation of whole slide imaging for frozen section diagnosis in surgical
pathology.
AB - BACKGROUND: Whole slide imaging (WSI) using high-resolution scanners is gaining
acceptance as a platform for consultation as well as for frozen section (FS)
evaluation in surgical pathology. We report results of an intra-observer
concordance study comparing evaluation of WSI of scanned FS microscope slides
with the original interpretation of the same microscope slides after an average
lag time of approximately 1-year. METHODS: A total of 70 FS cases (148 microscope
slides) originally interpreted by 2 pathologists were scanned at *20 using Aperio
CS2 scanner (Leica Biosystems, San Diego, CA, USA). Reports were redacted such
that the study pathologists reviewed images using eSlide Manager Healthcare
Network application (Leica Biosystems) accompanied by the same clinical
information available at the time of original FS evaluation. Discrepancies
between the original FS diagnosis and WSI diagnosis were categorized as major
(impacted patient care) or minor (no impact on patient care). RESULTS: Lymph
nodes, margins for head and neck cancer resections, and arthroplasty specimens to
exclude infection, were the most common FS specimens. The average wash-out
interval was 380 days (range: 303-466 days). There was one major discrepancy
(1.4% of 70 cases) where the original FS was interpreted as severe squamous
dysplasia, and the WSI FS diagnosis was mild dysplasia. There were two minor
discrepancies; one where the original FS was called focal moderate squamous
dysplasia and WSI FS diagnosis was negative for dysplasia. The second case was an
endometrial adenocarcinoma that was originally interpreted as Federation of
Gynecology and Obstetrics (FIGO) Grade I, while the WSI FS diagnosis was FIGO
Grade II. CONCLUSIONS: These findings validate and support the use of WSI to
provide interpretation of FS in our network of affiliated hospitals and
ambulatory surgery centers.
PMID- 26430536
TI - TissueCypher(TM): A systems biology approach to anatomic pathology.
AB - BACKGROUND: Current histologic methods for diagnosis are limited by intra- and
inter-observer variability. Immunohistochemistry (IHC) methods are frequently
used to assess biomarkers to aid diagnoses, however, IHC staining is variable and
nonlinear and the manual interpretation is subjective. Furthermore, the
biomarkers assessed clinically are typically biomarkers of epithelial cell
processes. Tumors and premalignant tissues are not composed only of epithelial
cells but are interacting systems of multiple cell types, including various
stromal cell types that are involved in cancer development. The complex network
of the tissue system highlights the need for a systems biology approach to
anatomic pathology, in which quantification of system processes is combined with
informatics tools to produce actionable scores to aid clinical decision-making.
AIMS: Here, we describe a quantitative, multiplexed biomarker imaging approach
termed TissueCypherTM that applies systems biology to anatomic pathology.
Applications of TissueCypherTM in understanding the tissue system of Barrett's
esophagus (BE) and the potential use as an adjunctive tool in the diagnosis of BE
are described. PATIENTS AND METHODS: The TissueCypherTM Image Analysis Platform
was used to assess 14 epithelial and stromal biomarkers with known diagnostic
significance in BE in a set of BE biopsies with nondysplastic BE with reactive
atypia (RA, n = 22) and Barrett's with high-grade dysplasia (HGD, n = 17).
Biomarker and morphology features were extracted and evaluated in the confirmed
BE HGD cases versus the nondysplastic BE cases with RA. RESULTS: Multiple image
analysis features derived from epithelial and stromal biomarkers, including
immune biomarkers and morphology, showed significant differences between HGD and
RA. CONCLUSIONS: The assessment of epithelial cell abnormalities combined with an
assessment of cellular changes in the lamina propria may serve as an adjunct to
conventional pathology in the assessment of BE.
PMID- 26430538
TI - A Case of Secondary Angiosarcoma of the Breast after Breast-conserving Surgery
and Radiation: Review of Radiologic and Pathologic Findings.
AB - Angiosarcoma of the breast is a rare and potentially life-threatening disease. It
can present as a palpable mass or subtle erythematous lesion, depending on the
predisposing clinical factors. Erythematous skin lesions may be confused for a
benign process, which may lead to a delay in diagnosis. We present a case of an
80-year-old woman who developed secondary angiosarcoma after undergoing breast
conserving therapy for Stage IA breast cancer. In this article, we review our
experience with a case of secondary angiosarcoma of the breast and discuss the
presentation, evaluation, and treatment of this disease. This case demonstrates
the importance of vigilance regarding erythematous or papular breast lesions in
the setting of prior local radiation.
PMID- 26430539
TI - Intrapetrous Anastomosis between the Internal Jugular Vein and the Superior
Petrosal Sinus: Cone Beam Computed Tomography Incidental Finding.
AB - This is a case report of a 62-year-old male who presented to the Ear, Nose, and
Throat clinic for a follow-up exam for hearing loss stemming from a fall from a
horse in his infancy. A Cone Beam Computed Tomography (CBCT) examination revealed
an intrapetrous communication between the internal jugular vein bulb and the
superior petrosal sinus. Three-dimensional bone and soft tissues volume
renderings were generated to demonstrate this incidental anatomical variant.
PMID- 26430540
TI - Malignant Transformation of Hepatic Adenoma in Glycogen Storage Disease Type-1a:
Report of an Exceptional Case Diagnosed on Surveillance Imaging.
AB - Hepatocellular adenoma is a heterogeneous group of benign neoplasms arising from
hepatocellular cells and can be subclassified into four major groups based on
genotypic and phenotypic characteristics. These four subtypes are hepatocyte
nuclear factor (HNF) 1alpha-inactivated, beta-catenin-activated, inflammatory,
and unclassified adenomas. Immunohistochemistry studies have demonstrated that
since beta-catenin-activated adenomas have a higher risk of malignant
transformation, the identification of the subtype of adenoma remains crucial in
patient management. However, malignant transformation of hepatic adenoma without
beta-catenin overexpression can be seen in 30-65% cases. We report a case of
malignant transformation of hepatic adenoma without overexpression of beta
catenin in a 31-year-old man with a known glycogen storage disease (GSD) Type-1a,
which was diagnosed on surveillance magnetic resonance imaging (MRI). The MRI
showed a mild interval increase in one lesion with relative stability of the
other adenomas. The lesion was presumed to be suspicious for a hepatocellular
carcinoma (HCC) and was confirmed on pathology.
PMID- 26430541
TI - Identification of Cardiac and Aortic Injuries in Trauma with Multi-detector
Computed Tomography.
AB - Blunt and penetrating cardiovascular (CV) injuries are associated with a high
morbidity and mortality. Rapid detection of these injuries in trauma is critical
for patient survival. The advent of multi-detector computed tomography (MDCT) has
led to increased detection of CV injuries during rapid comprehensive scanning of
stabilized major trauma patients. MDCT has the ability to acquire images with a
higher temporal and spatial resolution, as well as the capability to create
multiplanar reformats. This pictorial review illustrates several common and life
threatening traumatic CV injuries from a regional trauma center.
PMID- 26430542
TI - Multiple Mycotic Aneurysms of the Abdominal Aorta Illustrated on MDCT Scanner.
AB - Infective mycotic aneurysm of the aorta is a rare and life-threatening disease. A
patient presenting with constitutional symptoms and pulsatile abdominal mass
should raise a suspicion of mycotic aneurysm. Early detection of aortic mycotic
lesions in such patients should play a key role in the treatment of aortic
aneurysms. Multiple mycotic aneurysms of abdominal aorta in a young male are a
rare manifestation of the disease. Multidetector computerized tomography (CT) is
an essential tool in identifying the etiology, pathogenesis, protean
manifestations of systemic tuberculosis, and ultimately deciding the course of
treatment.
PMID- 26430543
TI - Radiologic-Pathologic Correlation: Metastatic Pulmonary Epithelioid
Hemangioendothelioma of Bone Primary.
AB - Epithelioid hemangioendothelioma is a rare vascular malignancy often
characterized by a clinically indolent course and delayed diagnosis. The authors
present the radiologic and pathologic features of a case of pulmonary epithelioid
hemangioendothelioma which was initially thought to be calcified granulomas.
PMID- 26430544
TI - Searching for the elusive mitochondrial longevity signal in C. elegans.
AB - There is a growing list of examples where perturbed mitochondrial function is
associated with increased longevity, yet the exact mechanisms have remained
elusive. This phenomenon was first documented, and has been studied most
extensively, in C. elegans. One prominent model proposed that lifespan extension
resulting from electron transport chain inhibition is due to induction of the
mitochondrial unfolded protein response. This model requires revision in light of
recent data showing that the mitochondrial unfolded protein response, as defined
by the field, is neither necessary nor sufficient for lifespan extension in C.
elegans. Several additional factors have been proposed to underlie this lifespan
extension, which is likely to be multifactorial and complex.
PMID- 26430545
TI - Acquired resistance to monepantel in C. elegans: What about parasitic nematodes?
AB - In 2008, Novartis Animal Health developed a new class of anthelmintics, the amino
acetonitrile derivatives (AAD) of which monepantel is the most prominent
compound. Monepantel was designed for the treatment of sheep against the
parasitic nematode Haemonchus contortus. Because monepantel acts through a
different mechanism, it is effective against nematodes that have acquired
resistance to long-standing anthelmintics. In order to benefit from a maximum
lifespan and efficacy of this new compound, the mode of action of monepantel
needs to be understood. Studies on the model nematode Caenorhabditis elegans led
to the identification of at least one target of monepantel: the monovalent cation
channel ACR-23. Here we comment on the effects of monepantel on C. elegans and on
the development of resistant parasitic nematode strains.
PMID- 26430546
TI - ICeE an interface for C. elegans experiments.
AB - An increasing number of laboratories are using the COPAS BiosortTM to implement
high-throughput approaches to tackle diverse biological problems. While providing
a powerful tool for generating quantitative data, the utility of the Biosort is
currently limited by the absence of resources for data management. We describe a
simple electronic database designed to allow easy storage and retrieval of
Biosort data for C. elegans, but that has a wide potential application for
organizing electronic files and data sets. ICeE is an Open Source application.
The code and accompanying documentation are freely available via the web at
http://www.ciml.univ-mrs.fr/EWBANK_jonathan/software.html.
PMID- 26430547
TI - From head to tail it's a 2 way street for neuro-immune communication.
AB - Animals need to be able to rapidly and effectively respond to changes in their
external and internal environment. To achieve this the nervous and immune systems
need to coordinate their responses, integrating multiple cues including presence
of potential pathogens, and availability of food. In our recent study (1) we
demonstrate that signaling by sensory neurons in the head using the classical
neurotransmitter serotonin can negatively regulate the rectal epithelial immune
response upon infection of C. elegans with the naturally occurring bacterial
pathogen Microbacterium nematophilum (M. nematophilum). The complicated nature of
the mammalian brain and immune system has made it difficult to identify the
molecular mechanisms mediating these interactions. With its simple, well
described, nervous system and a rapidly growing understanding of its immune
system, C. elegans has emerged as an excellent model to study the mechanisms by
which animals recognize pathogens and coordinate behavioral and cellular immune
responses to infection.
PMID- 26430548
TI - Membrane lipids and the endoplasmic reticulum unfolded protein response: An
interesting relationship.
AB - The unfolded protein response of the endoplasmic reticulum (UPR(ER)) is a
conserved signaling circuit that ensures ER protein homeostasis (proteostasis).
In the UPR(ER) of higher eukaryotes, multiple sensors cooperatively perceive
proteostatic disturbances in the ER lumen and induce downstream adaptive changes.
Besides direct proteotoxic insults, altered lipid profiles can also lead to
UPR(ER) activation, evidently because abnormal lipid composition impairs protein
folding. However, 2 recent studies propose an alternative mechanism of UPR(ER)
sensor activation. In one report, UPR(ER) activation occurred in cells expressing
UPR(ER) sensors lacking the very domains that sense unfolded proteins; the other
study found that Caenorhabditis elegans worms displayed UPR(ER) activation
without apparent proteostatic imbalance in the ER lumen. Collectively, these
studies suggest that lipid disequilibrium-activated UPR(ER) is not strictly
accompanied by compromised ER proteostasis and hint at a lipid membrane
monitoring role of the UPR(ER). These discoveries raise several important
questions: does the UPR(ER) monitor and maintain homeostasis of the ER membrane
and/or its lipids? In turn, does the UPR(ER) initiate downstream regulatory
events that specifically alleviate lipid or proteostatic imbalance? And what is
the physiological significance of proteostasis-independent UPR(ER) activation? In
this commentary, we will discuss these issues and highlight the utility of C.
elegans as an in vivo model to study lipid disequilibrium-induced UPR(ER) and
related pathways.
PMID- 26430549
TI - Investigating heart-specific toxicity of amyloidogenic immunoglobulin light
chains: A lesson from C. elegans.
AB - Abnormalities in protein folding are involved in many localized and systemic
diseases, all of which are characterized by insoluble amyloid formation and
deposition. In immunoglobulin light chain (LC) amyloidosis, the most frequent
systemic form of amyloidosis, the amyloid involvement of the heart dictates the
prognosis and the elucidation of the mechanism of heart targeting and toxicity is
essential for designing and testing new effective treatments. To this end, the
availability of an appropriate animal model is crucial. We recently described the
use of C. elegans as an innovative experimental system to investigate in vivo the
pathogenic effects of monoclonal LC. This idea stems from the knowledge that the
worm's pharynx is an "ancestral heart" with the additional ability to recognize
stressor compounds. The feeding of worms with LC purified from patients suffering
from cardiomyopathy, selectively and permanently impaired the pharyngeal
function. This irreversible damage resulted in time, in a significant reduction
in the lifespan of worms. We also reported that the ability of LC to generate
reactive oxygen species was associated with their toxic effects and was
counteracted by anti-oxidant compounds. This new nematode-based assay represents
a promising model for elucidating the heart-specific toxicity of LC and for a
rapid screening of new therapeutic strategies.
PMID- 26430550
TI - An intimate look at LET-23 EGFR trafficking in the vulval cells of live C.
elegans larvae.
AB - Precise cell fate specification is essential for organ formation. A simple view
is that one or several signal sending cells emit a ligand to a group of signal
receiving cells that express the corresponding receptor, which transduces the
signal through intracellular enzyme pathways. All these events must be spatio
temporally regulated to achieve the proper strength, duration and output of the
signaling pathways. In particular, the production and secretion of the ligand has
to be coordinated with the expression and accessibility of the receptor in the
signal receiving cells. Furthermore, removal of the ligand or receptor is key to
achieve proper signal termination and prevent excess cell differentiation and
proliferation. Improper regulation of any of these events may cause developmental
defects and human disease. C. elegans is an excellent model to systematically
identify genes that control the localization and activity of the Epidermal Growth
Factor Receptor (EGFR) homolog LET-23. To identify regulators of LET-23
trafficking, Haag et al. observed LET-23 localization in the vulva precursor
cells (VPCs) of RNAi treated larvae by live fluorescent microscopy. In this
comment, we provide an overview of the newly identified regulators of LET-23
trafficking and discuss the role of the Ezrin/Radixin/Moesin homolog ERM-1 as a
temporal regulator of EGFR signaling.
PMID- 26430551
TI - Microtubule dynamics followed through cell differentiation and tissue biogenesis
in C. elegans.
AB - Microtubules (MTs) are cytoskeletal filaments essential for many processes in
eukaryotic cells. Assembled of tubulin subunits, MTs are dynamic structures that
undergo successive and stochastic phases of polymerization and depolymerization,
a behavior called dynamic instability. Dynamic instability has been extensively
studied in cultured cells and in vitro using cytoplasmic extracts or
reconstituted MTs. However, how MTs behave in intact tissues and how their
dynamics are affected by or affect tissue function are poorly understood. Recent
advances in high-resolution live imaging have helped overcome technical
limitation in order to visualize MTs in intact living organisms including
Drosophila or Caenorhabditis elegans. We recently took advantage of the well
characterized development, small size and transparency of C. elegans to monitor
MT dynamics throughout tissue biogenesis with high spatial and temporal
resolution. Using the sex myoblast lineage that generates the egg-laying muscles
from 2 mitotic precursors, we identified selective dynamics in precursor versus
differentiated cells, and molecular regulation of MT dynamics changes that occur
during cell differentiation. We discuss here how this approach led to novel
insights into the regulation of MTs dynamics and organization in vivo.
PMID- 26430552
TI - Should I stay or should I go? Identification of novel nutritionally regulated
developmental checkpoints in C. elegans.
AB - After embryogenesis, developing organisms typically secure their own nutrients to
enable further growth. The fitness of an organism depends on developing when food
is abundant and slowing or stopping development during periods of scarcity.
Although several key pathways that link nutrition with development have been
identified, a mechanistic understanding of how these pathways coordinate growth
with nutritional conditions is lacking. We took advantage of the stereotyped
development and experimental accessibility of C. elegans to study nutritional
control of late larval development. We discovered that C. elegans larval
development is punctuated by precisely time checkpoints that globally arrest
growth when nutritional conditions are unfavorable. Arrest at the checkpoints is
regulated by insulin- and insulin-like signaling and steroid hormone signaling.
These pathways are conserved in mammals, suggesting that similar mechanisms could
regulate growth and development in humans. We highlight several implications of
our research, including quiescence of diverse cellular behaviors as an adaptive
response to unfavorable growth conditions, the existence of oscillatory
checkpoints that coordinate development across tissues, and the connections
between systemic and cell-autonomous regulators of nutritional response.
Together, our findings describe a fascinating developmental strategy in C.
elegans that we expect will not only provide insight into nutritional regulation
of development, but also into poorly understood cellular processes such as
quiescence and aging.
PMID- 26430553
TI - Evidence of a MOF histone acetyltransferase-containing NSL complex in C. elegans.
AB - Regulation of chromatin is a key process in the developmental control of gene
expression. Many multi-subunit protein complexes have been found to regulate
chromatin through the modification of histone residues. One such complex is the
MOF histone acetyltransferase-containing NSL complex. While the composition of
the human and Drosophila NSL complexes has been determined and the functions of
these complexes investigated, the existence of an equivalent complex in nematodes
such as Caenorhabditis elegans has not yet been explored. Here we summarise
evidence, from our own work and that of others, that homologues of NSL complex
components are found in C. elegans. We review data suggesting that nematode
proteins SUMV-1 and SUMV-2 are homologous to NSL2 and NSL3, respectively, and
that SUMV-1 and SUMV-2 may form a complex with MYS-2, the worm homolog of MOF. We
propose that these interactions suggest the existence of a nematode NSL-like
complex and discuss the roles of this putative NSL complex in worms as well as
exploring the possibility of crosstalk between NSL and COMPASS complexes via
components that are common to both. We present the groundwork from which a full
characterization of a nematode NSL complex may begin.
PMID- 26430554
TI - The soft genome.
AB - Caenorhabditis elegans (C. elegans) nematodes transmit small RNAs across
generations, a process that enables transgenerational regulation of genes. In
contrast to changes to the DNA sequence, transgenerational transmission of small
RNA-mediated responses is reversible, and thus enables "soft" or "flexible"
inheritance of acquired characteristics. Until very recently only introduction of
foreign genetic material (viruses, transposons, transgenes) was shown to directly
lead to inheritance of small RNAs. New discoveries however, demonstrate that
starvation also triggers inheritance of endogenous small RNAs in C.elegans.
Multiple generations of worms inherit starvation-responsive endogenous small
RNAs, and starvation also results in heritable extension of the progeny's
lifespan. In this Commentary paper we explore the intriguing possibility that
large parts of the genome and many additional traits are similarly subjected to
heritable small RNA-mediated regulation, and focus on the potential influence of
transgenerational RNAi on the worm's physiology. While the universal relevance of
this mechanism remains to be discovered, we will examine how the discoveries made
in worms already challenge long held dogmas in genetics and evolution.
PMID- 26430555
TI - Splicing factor SUP-12 and the molecular complexity of apparent cooperativity.
AB - The splicing factor SUP-12 from C. elegans, in combination with either ASD-1 or
FOX-1 from the Fox-1 (RBFOX) family, is required for generating a muscle-specific
isoform of the fibroblast growth factor receptor EGL-15. Biophysical techniques
have revealed the sequence preference for the RNA Recognition Motif (RRM) domain
from SUP-12 as well as the structural details of the RNA-bound complex. Detailed
genetics have identified a requisite need for the presence of both SUP-12 and ASD
1/FOX-1 to regulate the alternative splicing event, prompting speculation of a
cooperative mechanism between these proteins on binding RNA. In contrast, the
interplay between SUP-12 and ASD-1 suggests that although the RRM domains from
each protein are in direct contact on the egl-15 pre-mRNA, there is no simple
contribution of binding cooperativity. Evidence for an independent binding
mechanism by SUP-12 and ASD-1 will be discussed, including a model in which both
positive and negative contributions are balanced during complex assembly. The
ability to monitor tissue-specific alternative splicing in live nematodes will
continue to provide a powerful method to test in vivo mechanistic models derived
from atomic-level investigation.
PMID- 26430556
TI - SNF-10 connects male-derived signals to the onset of sperm motility in C.
elegans.
AB - Sperm from the nematode C. elegans gain motility during a process termed
activation, which they initiate in response to specific environmental signals.
During this process, a number of subcellular rearrangements occur, culminating in
an altered morphology that allows the cell to crawl toward and fertilize oocytes.
Both hermaphrodites and males produce sperm, and redundant, sex-biased pathways
regulate the sperm's activation. The male-derived signal for sperm activation
involves TRY-5, a trypsin-like serine protease in seminal fluid, but until
recently it was unknown what factors were active downstream of TRY-5. In our
recent paper, we reported the discovery of SNF-10, a solute carrier 6 (SLC6)
family protein that is expressed by sperm and connects the activation signal to
changes in sperm morphology and, ultimately, the onset of motility. Here, we
review our recent results, focusing on potential models for SNF-10's function in
C. elegans, and additionally discuss the role SLC6 transporters may play in male
reproductive biology from invertebrates to mammals.
PMID- 26430557
TI - Pharyngeal pumping inhibition and avoidance by acute exposure to high CO2 levels
are both regulated by the BAG neurons via different molecular pathways.
AB - Carbon dioxide (CO2) is a key molecule in many biological processes. Studies in
humans, mice, D. melanogaster, C. elegans, unicellular organisms and plants have
shed light on the molecular pathways activated by elevated levels of CO2.
However, the mechanisms that organisms use to sense and respond to high CO2
levels remain largely unknown. Previous work has shown that C. elegans quickly
avoid elevated CO2 levels using mechanisms that involve the BAG, ASE and AFD
neurons via cGMP- and calcium- signaling pathways. Here, we discuss our recent
finding that exposure of C. elegans to high CO2 levels leads to a very rapid
cessation in the contraction of the pharynx muscles. Surprisingly, none of the
tested CO2 avoidance mutants affected the rapid pumping inhibition response to
elevated CO2 levels. A forward genetic screen identified that the hid-1-mediated
pathway of dense core vesicle maturation regulates the pumping inhibition,
probably through affecting neuropeptide secretion. Genetic studies and laser
ablation experiments showed that the CO2 response of the pharyngeal muscle
pumping is regulated by the BAG neurons, the same neurons that mediate CO2
avoidance.
PMID- 26430558
TI - The two faces of TOE-2.
AB - The C. elegans Q lineage provides a unique context for studying how cells divide
asymmetrically to generate cells fated to die. The Q cell divides to form the Q.a
and Q.p neuroblasts, each of which divides to produce neurons and a cell that
dies by apoptosis; however, these neuroblasts employ different mechanisms to
divide asymmetrically.(1) We discovered 2 distinct roles for TOE-2, a protein
previously shown to be a target of the C. elegans ERK ortholog MPK-1, in
promoting apoptosis in each of these neuroblast divisions. In this commentary, we
discuss possible molecular mechanisms by which TOE-2 promotes apoptosis.
Specifically, we will discuss potential roles for TOE-2 interacting proteins, a
possible nuclear function for TOE-2, and a potential link to the Wnt pathway.
PMID- 26430559
TI - Syncytium biogenesis: It's all about maintaining good connections.
AB - At the end of mitosis, cells typically complete their division with cytokinesis.
In certain tissues however, incomplete cytokinesis can give rise to cells that
remain connected by intercellular bridges, thus forming a syncytium. Examples
include the germline of many species, from fruitfly to humans, yet the mechanisms
regulating syncytial formation and maintenance is unclear, and the biological
relevance of syncytial organization remains largely speculative. To better
understand these processes, we recently used the germline of Caenorhabditis
elegans as a model for syncytium development. Analysis of the germline syncytial
architecture throughout development revealed that it arises progressively during
larval growth and that it relies on the activity of 2 actomyosin scaffold
proteins of the Anillin family. Our work also showed that the gonad can sustain
elastic deformation when under mechanical stress and that this property may be
conferred by the malleability of syncytial openings. We suggest that elasticity
and resistance to mechanical stress constitutes a general property of syncytial
tissues.
PMID- 26430560
TI - The C. elegans embryonic fate specification factor EGL-18 (GATA) is reutilized
downstream of Wnt signaling to maintain a population of larval progenitor cells.
AB - In metazoans, stem cells in developing and adult tissues can divide
asymmetrically to give rise to a daughter that differentiates and a daughter that
retains the progenitor fate. Although the short-lived nematode C. elegans does
not possess adult somatic stem cells, the lateral hypodermal seam cells behave in
a similar manner: they divide once per larval stage to generate an anterior
daughter that adopts a non-dividing differentiated fate and a posterior daughter
that retains the seam fate and the ability to divide further. Wnt signaling
pathway is known to regulate the asymmetry of these divisions and maintain the
progenitor cell fate in one daughter, but how activation of the Wnt pathway
accomplished this was unknown. We describe here our recent work that identified
the GATA transcription factor EGL-18 as a downstream target of Wnt signaling
necessary for maintenance of a progenitor population of larval seam cells. EGL-18
was previously shown to act in the initial specification of the seam cells in the
embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an
embryonic fate specification factor to be reutilized later in life downstream of
a different regulator (Wnt signaling) to maintain a progenitor cell population.
These results support the use of seam cell development in C. elegans as a simple
model system for studying stem and progenitor cell biology.
PMID- 26430561
TI - The mysterious relationship between reproduction and longevity.
AB - A negative correlation between fertility and longevity has been documented in
many species under a variety of conditions, but the association is not always
observed,(1) leading to heated discussion about the nature of the reproduction
longevity relationship.(2) This debate is further fueled by the fact that no
genes or molecules have been clearly shown to link the 2 traits. A recent study
by Thondamal et al., in the nematode C. elegans has identified one potential
link. The authors showed that the steroid signaling pathway, which regulates
reproduction, is activated in response to dietary restriction (DR) and is in fact
required for DR-induced lifespan extension.(3) Steroid signaling mutants
subjected to DR not only failed to undergo lifespan extension but also exhibited
altered germline plasticity. Interestingly, the requirement for steroid signaling
was bypassed when germline plasticity was restored, suggesting that the DR
response is mediated, at least in part, by signals from the germline. In this
commentary, I discuss the implications of these findings. Several theories of
aging have proposed the existence of an energetic trade-off between reproduction
and lifespan,(4,5) but mechanistic details are lacking. I propose that revisiting
and dissecting at the molecular level the link between reproduction, nutrition,
and lifespan, will lead to a better understanding of the aging process and its
connection to reproduction.
PMID- 26430562
TI - Workshop report: Caenorhabditis nematodes as model organisms to study trait
variation and its evolution.
AB - A fundamental problem in biology is to understand how genome expression
translates into variation in molecular, cellular, developmental, physiological,
behavioral, or life-history traits. During the summer of 2014, worm biologists
with a keen interest in evolutionary biology and natural ecology met in Les
Treilles (France) to define the problems of trait variation better and to discuss
empirical approaches using Caenorhabditis species to address these problems.
Compared with other model organisms, Caenorhabditis has several advantages, such
as well-defined traits that can be subjected to highly controlled environmental
and genetic manipulation and the possibility for long-term experimental evolution
that can be coupled with genome-wide mapping of trait variation. The Les Treilles
workshop brought together researchers studying the evolution of phenotypic
plasticity, gene-networks, genome structure and population genetics, sex
determination and development in the laboratory, behavior and the life-history of
natural Caenorhabditis populations. Here, we outline the key aims of this
workshop and summarize the contributions of each participant.
PMID- 26430563
TI - Plasticity of chemoreceptor gene expression: Sensory and circuit inputs modulate
state-dependent chemoreceptors.
AB - Animals dramatically modify their chemosensory behaviors when starved, which
could allow them to alter and optimize their food-search strategies. Dynamic
changes in the gene expression of chemoreceptors may be a general mechanism
underlying food and state-dependent changes in chemosensory behaviors. In our
recent study,(1) we identified chemoreceptors in the ADL sensory neuron type of
C. elegans that are modulated by feeding state and food availability. Here, we
highllight our recent findings by which sensory inputs into ADL, neuronal outputs
from ADL, and circuit inputs from the RMG interneuron, which is electrically
connected to ADL, are required to regulate an ADL-expressed chemoreceptor. This
sensory and circuit-mediated regulation of chemoreceptor gene expression is
dependent on cell-autonomous pathways acting in ADL, e.g. KIN-29, DAF-2, OCR-2
and calcium signaling, and circuit inputs from RMG mediated by NPR-1. Based on
these findings, we propose an intriguing but speculative feedback modulatory
circuit mechanism by which sensory perception of food and internal state signals
may be coupled to regulate ADL-expressed chemoreceptors, which may allow animals
to precisely regulate and fine-tune their chemosensory neuron responses as a
function of feeding state.
PMID- 26430564
TI - Engineering new synaptic connections in the C. elegans connectome.
AB - Most of what we currently know about how neural circuits work we owe to methods
based on the electrical or optical recording of neural activity. This is changing
dramatically. First, the advent of optogenetic techinques has enabled precise
manipulation of the activity of specific neurons. Second, the development of
super-resolution methods for obtaining detailed maps of synaptic connectivity has
paved the way for uncovering the connectomes of entire brains or brain regions.
We describe a third and complementary new strategy for investigating and
manipulating neural circuits: the artificial insertion of new synapses into
existing neural circuits using genetic engineering tools. We have successfully
accomplished this in C. elegans. Thus, In addition to being the first animal with
an entirely mapped connectome, C. elegans is now also the first animal to have an
editable connectome. Variations on this approach may be applicable in more
complex nervous systems.
PMID- 26430565
TI - Translational activation maintains germline tissue homeostasis during adulthood.
AB - Adult tissue maintenance is achieved through a tightly controlled equilibrium of
2 opposing cell fates: stem cell proliferation and differentiation. In recent
years, the germ line emerged as a powerful in vivo model tissue to investigate
the underlying gene expression mechanisms regulating this balance. Studies in
numerous organisms highlighted the prevalence of post-transcriptional mRNA
regulation, which relies on RNA-targeting factors that influence mRNA fates (e.g.
decay or translational efficiency). Conserved translational repressors were
identified that build negative feedback loops to ensure one or the other cell
fate. However, to facilitate a fast and efficient transition between 2 opposing
cell fates, translational repression per se appears not to be sufficient,
suggesting the involvement of additional modes of gene expression regulation.
Cytoplasmic poly(A) polymerases (cytoPAPs) represent a unique class of post
transcriptional mRNA regulators that modify mRNA 3' ends and positively influence
cytoplasmic mRNA fates. We recently discovered that the 2 main cytoPAPs, GLD-2
and GLD-4, use distinct mechanisms to promote gene expression and that cytoPAP
mediated mRNA activation is important for regulating the size of the
proliferative germ cell pool in the adult Caenorhabditis elegans gonad. Here, we
comment on the different mechanisms of the 2 cytoPAPs as translational activators
in germ cell development and focus on their biological roles in maintaining the
balance between germline stem cell proliferation and differentiation in the
Caenorhabditis elegans gonad.
PMID- 26430566
TI - SLC30A10: A novel manganese transporter.
AB - Homozygous mutations in SLC30A10 cause familial parkinsonism associated with
manganese (Mn) retention. We recently identified SLC30A10 to be a cell surface
localized Mn efflux transporter and demonstrated that parkinsonism-causing
mutations block its intracellular trafficking and efflux function. In C. elegans,
SLC30A10 over-expression protected against Mn-induced lethality and dopaminergic
neurotoxicity, consistent with results in mammalian systems. Here, we present new
data about SLC30A10 function in C. elegans. SLC30A10 expression did not protect
worms against ZnSO4toxicity, suggesting that SLC30A10 does not mediate Zn export
in C. elegans. Furthermore, while a blast search identified 5 potential SLC30A10
homologs in worms (cdf-1, cdf-2, ttm-1 and toc-1; sequence identity <35%), knock
down of these genes showed a tendency of increased survival after Mn exposure
(although only ttm-1 was statistically significant), suggesting that the worm
homologs may function differently.
PMID- 26430567
TI - Trans-splicing in metazoans: A link to translational control?
AB - The trans-splicing of a spliced-leader RNA to a subset of mRNAs is a phenomenon
that occurs in many species, including Caenorhabditis elegans, and yet the
driving force for its evolution in disparate groups of animals remains unclear.
Polycistronic mRNA resulting from the transcription of operons is resolved via
trans-splicing, but operons comprise only a sub-set of trans-spliced genes. Using
the marine chordate, Oikopleura dioica, we recently tested the hypothesis that
metazoan operons accelerate recovery from growth arrest. We found no supporting
evidence for this in O. dioica. Instead we found a striking relationship between
trans-splicing and maternal mRNA in O. dioica, C. elegans and the ascidian, Ciona
intestinalis. Furthermore, in O. dioica and C. elegans, we found evidence to
suggest a role for mTOR signaling in the translational control of growth-related,
trans-spliced maternal mRNAs. We propose that this may be a mechanism for
adjusting egg number in response to nutrient levels in these species.
PMID- 26430568
TI - 20 Years of unc-119 as a transgene marker.
AB - This fall marks 20 years since the cloning of unc-119 was reported. Despite
having a strong phenotype that makes animals somewhat difficult to grow and
handle, unc-119 mutant rescue has become one of the most frequently-used markers
for C. elegans transformation. In this Commentary, I describe the history of how
unc-119 rescue traveled through the worm community, contributing to the
development of transgene methods in C. elegans.
PMID- 26430569
TI - In the proper context: Neuropeptide regulation of behavioral transitions during
food searching.
AB - Neuromodulation enables transient restructuring of anatomically fixed neural
circuits, generating alternate outputs and distinct states that allow for
flexible organismal responses to changing conditions. We recently identified a
requirement for the neuropeptide-like protein NLP-12, a Caenorhabditis elegans
homolog of mammalian Cholecystokinin (CCK), in the control of behavioral
responses to altered food availability. We showed that deletion of nlp-12 impairs
turning during local food searching while nlp-12 overexpression is sufficient to
induce deep body bends and enhance turning. nlp-12 is solely expressed in the DVA
interneuron that is located postsynaptic to the dopaminergic PDE neurons and
presynaptic to premotor and motor neurons, well-positioned for modulating
sensorimotor tasks. Interestingly, DVA was previously implicated in a NLP-12
mediated proprioceptive feedback loop during C. elegans locomotion. Here, we
discuss the modulatory effects of NLP-12 with an emphasis on the potential for
circuit level integration with olfactory information about food availability. In
addition, we propose potential mechanisms by which DVA may integrate distinct
forms of sensory information to regulate NLP-12 signaling and mediate context
dependent modulation of the motor circuit.
PMID- 26430570
TI - Interfacing mitochondrial biogenesis and elimination to enhance host pathogen
defense and longevity.
AB - Mitochondria are highly dynamic and semi-autonomous organelles, essential for
many fundamental cellular processes, including energy production, metabolite
synthesis and calcium homeostasis, among others. Alterations in mitochondrial
activity not only influence individual cell function but also, through non-cell
autonomous mechanisms, whole body metabolism, healthspan and lifespan. Energy
homeostasis is orchestrated by the complex interplay between mitochondrial
biogenesis and mitochondria-selective autophagy (mitophagy). However, the
cellular and molecular pathways that coordinate these 2 opposing processes
remained obscure. In our recent study, we demonstrate that DCT-1, the
Caenorhabditis elegans homolog of the mammalian BNIP3 and BNIP3L/NIX, is a key
mediator of mitophagy, and functions in the same genetic pathway with PINK-1 and
PDR-1 (the nematode homologs of PINK1 and Parkin respectively) to promote
longevity and prevent cell damage under stress conditions. Interestingly,
accumulation of damaged mitochondria activates SKN-1 (SKiNhead-1), the nematode
homolog of NRF2, which in turn initiates a compensatory retrograde signaling
response that impinges on both mitochondrial biogenesis and removal. In this
commentary, we discuss the implications of these new findings in the context of
innate immunity and aging. Unraveling the regulatory network that governs the
crosstalk between mitochondrial biogenesis and mitophagy will enhance our
understanding of the molecular mechanisms that link aberrant energy metabolism to
aging and disease.
PMID- 26430572
TI - 18F-FDG PET/CT Imaging of Gallbladder Adenocarcinoma - A Pictorial Review.
AB - Gallbladder adenocarcinoma is an uncommon and serious disease. The primary
disease grows rapidly with local invasion into the liver and with distant spread
to lymph nodes. It is often detected late, due to which management can be
challenging. Despite routine use of computed tomography (CT) and ultrasonography
(US) for detection, magnetic resonance imaging (MRI) is often considered for a
detailed assessment of the anatomic behavior of these tumors. We share three
cases where 18-FDG PET/CT played a role in management thereof.
PMID- 26430571
TI - The SKN-1 hunger games: May the odds be ever in your favor.
AB - Animals must continually assess nutrient availability to develop appropriate
strategies for survival and reproductive success. It is no secret that
nutritional state plays a large role in both aging and health.(1-7) Appropriate
cellular energy usage is not only crucial for animal starvation survival, but is
also important for diseases such as obesity and cancer, which characteristically
have metabolic dysfunction.(8-10) C. elegans are exceptionally well poised to
handle bouts of starvation as resource availability in the wild varies
greatly.(11,12) We recently discovered an evolutionarily conserved pathway,
regulated by the cytoprotective transcription factor SKN-1/Nrf2, which integrates
diet composition and availability with utilization for survival.(13,14) These
responses have potent impact on organismal physiology and remarkably are
influenced by current and parental life history events, including choice of diet.
In this commentary we will focus on recent insights concerning dietary intake and
the impact that this can have throughout the life history of the nematode,
Caenorhabditis elegans. In light of the strong impact that diet plays throughout
life we urge caution when interpreting previous studies that make use of only one
diet and suggest a reinvestigation utilizing a different diet is warranted.
PMID- 26430573
TI - Therapeutic Potential of Adjuvant Stereotactic Body Radiotherapy for Gallbladder
Cancer.
AB - Surgical treatment remains the only curative treatment for gallbladder cancer.
However, even after liver resection, locoregional failure seems to be a
significant problem. While there is no Level I evidence, multiple studies have
shown benefit for adjuvant radiation in high-risk patients. After extensive liver
resection, tolerance to conventional chemoradiation may be limited by potential
liver toxicity. Stereotactic body radiotherapy has been used safely and
effectively in hepatobiliary malignancies. We present a case report, highlighting
the potential therapeutic role of adjuvant stereotactic body radiotherapy (SBRT)
for gallbladder cancer.
PMID- 26430574
TI - An Unusual MRI Appearance of Osseous Metastases.
AB - Bone metastases can present in a wide variety of appearances across all imaging
modalities. We present a unique appearance of a distal femoral metastasis in a
patient who initially complained of knee pain. The radiographic and CT findings
were initially suspicious for calcium pyrophosphate deposition (CPPD)
arthropathy; however, an MRI demonstrated multiple lesions with a lamellated
appearance confirmed on biopsy to be metastatic disease. This unusual lamellated
appearance has not been previously described. We present this case to help
distinguish this entity radiographically and better classify this finding as a
manifestation of metastatic disease.
PMID- 26430575
TI - Surgical Management of Sacral Chordomas: Illustrative Cases and Current
Management Paradigms.
AB - Sacral chordomas represent more than 50% of all sacral tumors. These slow
growing, malignant lesions present insidiously and are often large and intimately
involved with sacral neurovascular and pelvic structures. En bloc resection is
the only well-established predictor of progression-free survival. Optimal
surgical management requires a complex multi-disciplinary approach. Here, we
describe two cases of sacral chordoma and review current management paradigms.
PMID- 26430576
TI - Association of Diabetic Neuropathy with Duration of Type 2 Diabetes and Glycemic
Control.
AB - INTRODUCTION: Diabetes mellitus is associated with severe microvascular and
macrovascular complications with major implications for public health. Diabetic
neuropathy is a very problematic complication of diabetes mellitus. It is
associated with severe morbidity, mortality, and a huge economic burden. The
present study was designed with two aims: 1) to analyze the association of
diabetic neuropathy with the glycemic index (levels of fasting blood glucose,
random blood glucose, and Hb1Ac) in patients with Type 2 diabetes, and 2) to
analyze the association of diabetic neuropathy with time passed since the
diagnosis of diabetes. METHODS: This case-control study was undertaken between
June 2013 and February 2015 in the Armed Forces Institute of Rehabilitation
Medicine (AFIRM), Rawalpindi, Pakistan. Type 2 diabetics with an age range of 30
60 years were recruited from outpatient departments of AFIRM, Rawalpindi. Data
were collected and recorded on a form with four sections recording the following:
1) demographics of patients and number of years passed since diagnosis of
diabetes; 2) clinical examination for touch, pressure, power, pain, vibration,
and ankle reflex; 3) nerve conduction studies for motor components of the common
peroneal nerve and tibial nerve and the sensory component of median nerve and
sural nerve; 4) glycemic index, including fasting blood glucose levels (BSF),
random blood glucose (BSR) levels, and HbA1c levels. Data were analyzed in SPSS
v. 20. Chi-square and phi statistics and logistic regression analysis were run to
analyze associations between diabetic neuropathy and time passed since diagnosis
of diabetes and glycemic index. RESULTS: In total, 152 patients were recruited.
One-half of those patients had neuropathy (76 patients) and the other half (76
patients) had normal nerve function. The mean (standard deviation [SD]) duration
of diabetes was nine years (6.76), BSF levels 7.98 mmol/l (2.18), BSR 9.5 mmol/l
(3.19), and HbA1c 6.5% (2.18). Logistic regression analysis predicted 87.5% of
the model correctly. Duration since the diagnosis of diabetes and HbA1c levels
were significantly associated with the diagnosis of neuropathy in diabetics.
CONCLUSION: The presence of diabetic neuropathy was significantly associated with
HbA1c levels and the duration of diabetes.
PMID- 26430577
TI - A Report on the Clinical Outcome after High-Dose Rate (HDR) Brachytherapy as
Monotherapy in Early Prostate Cancer.
AB - BACKGROUND: To report the clinical outcome after a single implant, high dose rate
(HDR) brachytherapy in early prostate cancer. MATERIALS AND METHODS: All
clinically localized prostate cancer patients who underwent high-dose rate (HDR)
brachytherapy as monotherapy (no external beam radiotherapy) from February 2006
to September 2011 were analyzed prospectively. Acute and chronic toxicity were
assessed as per Common Terminology Criteria for Adverse Events (CTCAE), Version
4.03. Biochemical recurrence was analyzed using the Kaplan Meir method. A log
rank analysis was done to compare the factors affecting the outcome. RESULTS:
Forty-four patients with organ-confined prostate cancer opted for HDR
brachytherapy between February 2006 to September 2011 with a median follow-up of
68 months The five-year biochemical recurrence-free survival (bRFS) rate was
91%. Late Grade 2 genitourinary (GU) toxicity was observed in 9% of patients. The
predictors of late Grade 2 GU toxicity were urethra V125 >= 0.2 cc (urethral
volume receiving >= 125% of the prescribed dose) and PTV 150 >= 35% ( planning
target volume receiving >= 150% of the prescribed dose) with p-value = 0.001 and
0.002, respectively. Erectile function was preserved in 72% of the patients who
had Grade 0-1 erectile dysfunction before brachytherapy. CONCLUSION: HDR
brachytherapy in early prostate cancer results in high local control rates with
minimal side-effects.
PMID- 26430578
TI - Human Nocardia Infections: A Review of Pulmonary Nocardiosis.
AB - Human nocardiosis may present as an acute or a chronic infection. Although a
saprophyte Nocardia spp are responsible for superficial skin infections,
pulmonary infections, and disseminated nocardiosis usually involving patients who
are immunosuppressed and debilitated. Infections in immunocompetent individuals
are usually chronic and present non-specific symptoms. Invasive and disseminated
nocardiosis is common among patients with weakened cellular immune systems.
Clinical diagnosis of pulmonary nocardiosis is difficult owing to the similarity
of its presentation with other respiratory pathogens that include Actinomycetes
members and Mycobacterium tuberculosis. Laboratory diagnosis of human nocardiosis
is plagued by the fact that a culture of Nocardia spp requires prolonged
incubation periods for isolation which most laboratories fail to follow. The lack
of clinical, laboratory, and epidemiological data on the incidence of nocardiosis
in humans undermines its significance as a potential pathogen. This review
attempts to reexamine the pathogenic potential of Nocardia in human infections.
PMID- 26430579
TI - Preservation of Pituitary Function after Endonasal Craniopharyngioma Surgery:
Case Report and Review of the Literature.
AB - Craniopharyngiomas comprise approximately 3% of all intracranial tumors.
Preservation of pituitary function after resection represents a significant
challenge due to their location in the anterior skull base and aggressive local
behavior. We report a case of a 79-year-old woman with a large suprasellar
craniopharyngioma who presented with visual loss. MRI revealed a suprasellar
cystic mass with mass effect on the optic chiasm and pituitary gland. Following
endoscopic endonasal gross total resection of the tumor, the patient's pituitary
function returned to normal.
PMID- 26430580
TI - Surgical Management of Musculoskeletal Injuries after 2015 Nepal Earthquake: Our
Experience.
AB - We report our experience of handling 80 major musculoskeletal injuries in a brief
span of three days immediately after the major earthquake of Nepal in April 2015.
Planning, proper utilization of resources, and prioritizing the patients for
surgical intervention is highlighted. The value of damage control by orthopaedics
in these disasters is discussed. Timely and appropriate surgical treatment by a
skilled orthopaedic team not only can save these injured limbs but also the lives
of the victims of a major disaster.
PMID- 26430581
TI - Cervical Epidural Hematoma after Chiropractic Spinal Manipulation Therapy in a
Patient with an Undiagnosed Cervical Spinal Arteriovenous Malformation.
AB - Spinal epidural hematoma (SEH) occurring after chiropractic spinal manipulation
therapy (CSMT) is a rare clinical phenomenon. Our case is unique because the
patient had an undiagnosed cervical spinal arteriovenous malformation (AVM)
discovered on pathological analysis of the evacuated hematoma. Although the
spinal manipulation likely contributed to the rupture of the AVM, there was no
radiographic evidence of the use of excessive force, which was seen in another
reported case. As such, patients with a known AVM who have not undergone surgical
intervention should be cautioned against symptomatic treatment with CSMT, even if
performed properly. Regardless of etiology, SEH is a surgical emergency and its
favorable neurological recovery correlates inversely with time to surgical
evacuation.
PMID- 26430582
TI - Vertebral Artery Dissection and Cord Infarction - an Uncommon Cause of Brown
Sequard and Horner Syndromes.
AB - This case report illustrates the neuroanatomy and neurovascular anatomy of the
cervical spinal cord by exploring the pathophysiology of cervical cord infarction
secondary to vertebral artery injury. The spinal cord is made up of several
important tracts, including the dorsal column medial lemniscus system,
corticospinal tracts, and the anterolateral system. Injury to one or more of
these pathways can result in localizing neurological symptoms. Also contributing
to the complexity of spinal vascular pathophysiology is the considerable
variation to the cervical cord vascular anatomy. Understanding spinal cord
function and neuroanatomy can aid in prompt diagnosis and management of ischemic
cord lesions. In combination with a thorough clinical exam, advanced imaging
techniques, such as diffusion tensor imaging, can not only localize the injury
but also potentially help predict functional outcome.
PMID- 26430583
TI - Effect of DNA Methylation in Various Diseases and the Probable Protective Role of
Nutrition: A Mini-Review.
AB - DNA methylation, a process of adding a methyl group to DNA done by a DNA
methyltransferase is a heritable (epigenetic) alteration leading to cancer,
atherosclerosis, nervous disorders (Imprinting disorders), and cardiovascular
diseases. The role of nutrition in DNA methylation is revealed by identification
of methyl variable positions (MVP) on DNA. These regions are more susceptible to
DNA methylations. Nutritional supplementation of folic acid and methionine in
utero and in adults decreased epigenetic modifications due to its role in DNA
metabolism (one carbon metabolism). Thus, in utero and adult supplementation of
folic acid and methionine may reduce DNA methylation. This review attempts to
highlight the process of DNA methylation, its effect on various diseases, and the
probable protective role of nutrition.
PMID- 26430585
TI - Endonasal Endoscopic Transsphenoidal Resection of Tuberculum Sella Meningioma
with Anterior Cerebral Artery Encasement.
AB - Anterior cerebral artery (ACA) encasement is often considered a contraindication
for an endonasal endoscopic transsphenoidal approach. We report a patient with a
tuberculum sella meningioma with ACA encasement, in whom a gross total excision
was achieved through an endonasal endoscopic transsphenoidal transtuberculum,
transplanum approach. The tumor was sharply dissected along the left ACA using
meticulous bimanual sharp dissection after internal decompression. Moreover, the
medial optic canals were opened and the optic nerves decompressed. A gasket seal
closure with a nasoseptal flap was performed, and the patient was discharged on
postoperative day four with improved vision. This case highlights the ability to
remove planum and tuberculum meningiomas with vascular encasement through an
endonasal endoscopic approach with the potential for safe vascular dissection.
The absence of luminal narrowing can be used to assure the likelihood of a safe
arachnoid plane.
PMID- 26430584
TI - Hand Hygiene: Knowledge and Attitudes of Fourth-Year Clerkship Medical Students
at Alfaisal University, College of Medicine, Riyadh, Saudi Arabia.
AB - INTRODUCTION: Little is known about the clerkship (clinical) medical students'
knowledge of hand hygiene as the single most important precautionary measure to
reduce nosocomial healthcare-associated infections. The aim of this study is to
explore the knowledge of, and attitudes towards, hand hygiene practices among
fourth-year clerkship medical students at Alfaisal University, College of
Medicine, Riyadh, Saudi Arabia. MATERIALS AND METHODS: A cross-sectional, paper
based, Yes/No formatted questionnaire was administered to explore the students'
knowledge of, and attitudes towards, hand hygiene practices. Data were decoded in
Microsoft Excel sheet and presented as numbers and percentages. RESULTS: One
hundred and eleven students (n=111/147) participated in the questionnaire
(response rate: 76%). Although the majority of students had a fair knowledge of
hand hygiene practices, a number of them had some misconceptions. Only 14% of
students correctly agreed to the statement: "Traditional hand washing (water,
plus regular soap) decreases the number of germs." Furthermore, only 32% of
students correctly answered that "hand washing with a regular soap, instead of an
antiseptic soap, is better in limiting the transmission of clostridium difficile
infections". Almost all students (93%) agreed to the importance of hand hygiene
education in medical curricula and its awareness in healthcare centers. Despite
the importance of hand hygiene, only 13% of students reviewed the respective WHO
and CDC guidelines before starting their clinical training in the teaching
hospital. DISCUSSION: The students' inadequate knowledge about hand hygiene needs
to be enriched by well-structured curricular and extra-curricular programs as
well as more positive attitudes by healthcare workers.
PMID- 26430586
TI - Prospective Evaluation of Ventriculostomy Infections.
AB - INTRODUCTION: Hospital-acquired infections associated with external drainage of
ventricular cerebrospinal fluid (CSF) are a significant source of concern for the
patients and the provider team alike. Traditional rates of ventriculostomy
infection range from 10-17% in a time-dependent fashion. Changing physician and
nursing practices fueled this concern over infections. OBJECTIVE: We sought to
prospectively identify the risk factors associated with ventriculostomy
infections as part of a quality assurance project. METHODS: One hundred
consecutive patients were evaluated and data were collected on 91. The primary
indications for ventriculostomy were subarachnoid hemorrhage (46%), intracerebral
hemorrhage (24%), and trauma (22%). Variables prospectively evaluated included
pre-incision antibiotics, sterile technique bundling, setting of placement
(operating room versus intensive care unit), experience of operator (attending,
resident, or physician assistant), catheter type (antibiotic impregnated or not),
use of a post-insertion dressing, and in-dwell time of the catheter. RESULTS:
There was only one infection in 91 patients (1.1%). This infection occurred in a
patient without an antibiotic-impregnated catheter that was inserted by a
resident physician. Compliance with pre-insertion antibiotics was very high, but
most other variables had modest deviations in compliance. CONCLUSION: Infection
rate related to external ventricular drainage is very low. Our data suggest that
non-antibiotic impregnated catheters may be associated with infection, but that
other variables thought to be critical may be of less value.
PMID- 26430587
TI - Social Media and the Online World: The New Frontier.
PMID- 26430588
TI - Annulus Fibrosus Can Strip Hyaline Cartilage End Plate from Subchondral Bone: A
Study of the Intervertebral Disk in Tension.
AB - Study Design Biomechanical study on cadaveric spines. Objective Spinal bending
causes the annulus to pull vertically (axially) on the end plate, but failure
mechanisms in response to this type of loading are poorly understood. Therefore,
the objective of this study was to identify the weak point of the intervertebral
disk in tension. Methods Cadaveric motion segments (aged 79 to 88 years) were
dissected to create midsagittal blocks of tissue, with ~10 mm of bone superior
and inferior to the disk. From these blocks, 14 bone-disk-bone slices (average
4.8 mm thick) were cut in the frontal plane. Each slice was gripped by its bony
ends and stretched to failure at 1 mm/s. Mode of failure was recorded using a
digital camera. Results Of the 14 slices, 10 failed by the hyaline cartilage
being peeled off the subchondral bone, with the failure starting opposite the
lateral annulus and proceeding medially. Two slices failed by rupturing of the
trabecular bone, and a further two failed in the annulus. Conclusions The hyaline
cartilage-bone junction is the disk's weak link in tension. These findings
provide a plausible mechanism for the appearance of bone and cartilage fragments
in herniated material. Stripping cartilage from the bony end plate would result
in the herniated mass containing relatively stiff cartilage that does not easily
resorb.
PMID- 26430589
TI - Asymptomatic Stenosis in the Cervical and Thoracic Spines of Patients with
Symptomatic Lumbar Stenosis.
AB - Study Design Retrospective study. Objective Studies on age-related degenerative
changes causing concurrent stenoses in the cervical, thoracic, and lumbar spines
(triple stenosis) are rare in the literature. Our objectives were to determine:
(1) the incidence of asymptomatic radiologic cervical and thoracic stenosis in
elderly patients with symptomatic lumbar stenosis, (2) the incidence of
concurrent radiologic spinal stenosis in the cervical and thoracic spines, and
(3) the radiologic features of cervical stenosis that might predict concurrent
thoracic stenosis. Methods Whole-spine T2 sagittal magnetic resonance images of
patients older than 80 and diagnosed with lumbar spinal stenosis between January
2003 and January 2012 were evaluated retrospectively. We included patients with
asymptomatic spondylotic cervical and thoracic stenosis. We measured the
anteroposterior diameters of the vertebral body, bony spinal canal, and spinal
cord, along with the Pavlov ratio and anterior or posterior epidural stenosis at
the level of the disk for each cervical and thoracic level. We compared the
radiologic parameters between the subgroups of cervical stenosis with and without
thoracic stenosis. Results Among the 460 patients with lumbar stenosis, 110
(23.9%) had concurrent radiologic cervical stenosis and 112 (24.3%) had
concurrent radiologic thoracic stenosis. Fifty-six patients (12.1%) had combined
radiologic cervical and thoracic stenosis in addition to their symptomatic lumbar
stenosis (triple stenosis). Anterior epidural stenosis at C7-T1 was associated
with a high prevalence of thoracic stenosis. Conclusions It appears that
asymptomatic radiologic cervical and thoracic stenosis is common in elderly
patients with symptomatic lumbar stenosis.
PMID- 26430590
TI - Distal Junctional Disease after Occipitothoracic Fusion for Rheumatoid Cervical
Disorders: Correlation with Cervical Spine Sagittal Alignment.
AB - Study Design Retrospective radiographic study. Objective We have performed
occipitothoracic (OT) fusion for severe rheumatoid cervical disorders since 1991.
In our previous study, we reported that the distal junctional disease occurred in
patients with fusion of O-T4 or longer due to increased mechanical stress. The
present study further evaluated the association between the distal junctional
disease and the cervical spine sagittal alignment. Methods Among 60 consecutive
OT fusion cases between 1991 and 2010, 24 patients who underwent O-T5 fusion were
enrolled in this study. The patients were grouped based on whether they developed
postoperative distal junctional disease (group F) or not (group N). We measured
pre- and postoperative O-C2, C2-C7, and O-C7 angles and evaluated the association
between these values and the occurrence of distal junctional disease. Results
Seven (29%) of 24 patients developed adjacent-level vertebral fractures as distal
junctional disease. In group F, the mean pre- and postoperative O-C2, C2-C7, and
O-C7 angles were 12.1 and 16.8, 7.2 and 11.2, and 19.4 and 27.9 degrees,
respectively. In group N, the mean pre- and postoperative O-C2, C2-C7, and O-C7
angles were 15.9 and 15.0, 4.9 and 5.8, and 21.0 and 20.9 degrees, respectively.
There were no significant differences between the two groups. The difference in
the O-C7 angle (postoperative angle - preoperative angle) in group F was
significantly larger than that in group N (p = 0.04). Conclusion Excessive
correction of the O-C7 angle (hyperlordotic alignment) is likely to cause
postoperative distal junctional disease following the OT fusion.
PMID- 26430591
TI - A Worldwide Analysis of the Reliability and Perceived Importance of an Injury to
the Posterior Ligamentous Complex in AO Type A Fractures.
AB - Study Design Survey of spine surgeons. Objective To determine the reliability
with which international spine surgeons identify a posterior ligamentous complex
(PLC) injury in a patient with a compression-type vertebral body fracture (type
A). Methods A survey was sent to all AOSpine members from the six AO regions of
the world. The survey consisted of 10 cases of type A fractures (2 subtype A1, 2
subtype A2, 3 subtype A3, and 3 subtype A4 fractures) with appropriate imaging
(plain radiographs, computed tomography, and/or magnetic resonance imaging), and
the respondent was asked to identify fractures with a PLC disruption, as well as
to indicate if the integrity of the PLC would affect their treatment
recommendation. Results Five hundred twenty-nine spine surgeons from all six AO
regions of the world completed the survey. The overall interobserver reliability
in determining the integrity of the PLC was slight (kappa = 0.11). No substantial
regional or experiential difference was identified in determining PLC integrity
or its absence; however, a regional difference was identified (p < 0.001) in how
PLC integrity influenced the treatment of type A fractures. Conclusion The
results of this survey indicate that there is only slight international
reliability in determining the integrity of the PLC in type A fractures. Although
the biomechanical importance of the PLC is not in doubt, the inability to
reliably determine the integrity of the PLC may limit the utility of the M1
modifier in the AOSpine Thoracolumbar Spine Injury Classification System.
PMID- 26430592
TI - Surgical Anatomy of the Uncinate Process and Transverse Foramen Determined by
Computed Tomography.
AB - Study Design Computed tomography-based cohort study. Objective Although there are
publications concerning the relationship between the vertebral artery and
uncinate process, there is no practical guide detailing the dimensions of this
region to use during decompression of the intervertebral foramen. The purpose of
this study is to determine the anatomic parameters that can be used as a guide
for thorough decompression of the intervertebral foramen. Methods Fifty-one
patients with three-dimensional computed tomography scans of the cervical spine
from 2003 to 2012 were included. On axial views, we measured the distance from
the midline to the medial and lateral cortices of the pedicle bilaterally from C3
to C7. On coronal reconstructed views, we measured the minimum height of the
uncinate process from the cranial cortex of the pedicle adjacent to the posterior
cortex of vertebral body and the maximal height of the uncinate process from the
cranial cortex of the pedicle at the midportion of the vertebral body bilaterally
from C3 to C7. Results The mean distances from midline to the medial and lateral
cortices of the pedicle were 10.1 +/- 1.3 mm and 13.9 +/- 1.5 mm, respectively.
The mean minimum height of the uncinate process from the cranial cortex of the
pedicle was 4.6 +/- 1.6 mm and the mean maximal height was 6.1 +/- 1.7 mm.
Conclusions Our results suggest that in most cases, one can thoroughly decompress
the intervertebral foramen by removing the uncinate out to 13 mm laterally from
the midline and 4 mm above the pedicle without violating the transverse foramen.
PMID- 26430593
TI - Impact of Preoperative Hematocrit Level on Length of Stay after Surgery on the
Lumbar Spine.
AB - Study Design Retrospective case series. Objective Recent studies suggest that
baseline hematocrit (Hct) levels may affect the surgical outcomes after
orthopedic procedures. The authors examined whether preoperative Hct values had a
significant effect on the hospital length of stay (LoS) after lumbar spinal
procedures. Methods We retrospectively reviewed patients who underwent routine
lumbar spine procedures from November 2012 through September 2013. Patients were
included if they had both a baseline Hct and hospital LoS recorded. Patients were
divided into two groups: those with an Hct >= 40% (nonanemic) and those with an
Hct < 40% (anemic). LoS after surgery was evaluated for each group. Results One
hundred seventeen patients underwent lumbar spine procedures for lumbar stenosis
(n = 34), symptomatic lumbar disk herniation (n = 39), lumbar spondylolisthesis
(n = 26), lumbar adjacent segment disease (n = 8), or symptomatic recurrent
lumbar disk herniation (n = 10). Mean LoS was 3.3 and 2.4 days in anemic (27
patients) and nonanemic groups (90 patients), respectively (p = 0.02). The linear
regression analysis demonstrated that a decrease in Hct was associated with a
longer stay. A decrease from preoperative to postoperative day 1 Hct of 3.5
points resulted in an increased LoS of 1 day (R (2) = 0.145; p = 0.002). The
correlation of Hct decrease with longer LoS remained (beta = 0.167, p = 0.006)
after adjusting for other variables with multivariate regression analysis.
Conclusions Lower preoperative Hct or a substantial decrease in Hct may
contribute to longer hospitalization after lumbar spine surgery. These findings
should prompt an investigation into the strategies for optimizing Hct levels in
patients with preoperative anemia prior to lumbar spine procedures.
PMID- 26430594
TI - The Occupancy of the Components in the Cervical Spine and Their Changes with
Extension and Flexion.
AB - Study Design Retrospective case series. Objectives The kinematics of the cervical
spine has been investigated by many researchers. However, the occupancy of the
disk bulges, spinal cord, ligamentum flavum, and the rest of the canal as well as
the changes of these structures with motion have not yet been investigated. The
goal of this study is to investigate these dynamic changes. Methods The kinetic
magnetic resonance images of 248 patients (124 men and 124 women) were evaluated,
and the occupancy of each structure for each cervical level at neutral, flexion,
and extension were calculated. Results Whole canal anteroposterior (AP) diameters
showed significant differences between neutral-extension and flexion-extension at
the C4-C5 and C5-C6 levels (p < 0.05). The mean disk bulges showed significant
differences between neutral-flexion and flexion-extension at the C4-C5, C5-C6, C6
C7, and C7-T1 levels (p < 0.01). The mean spinal canal AP diameter showed
significant differences between flexion-extension and neutral-extension at the C3
C4, C4-C5, C5-C6, and C6-C7 levels (p < 0.05). There were significant differences
between neutral-flexion at the C4-C5, C5-C6, and C6-C7 levels (p < 0.05). The
mean thickness of the ligamentum flavum showed significant differences between
flexion-extension at the C3-C4, C4-C5, C5-C6, and C6-C7 levels (p < 0.001). There
were significant differences between neutral-extension at the C3-C4 and C5-C6
levels (p < 0.05). There were significant differences between neutral-flexion at
the C5-C6 and C6-C7 levels (p < 0.05). The mean thickness of the spinal cord
showed significant differences between neutral-flexion at the C2-C3 and C3-C4
levels (p < 0.05). There were significant differences between flexion-extension
at the C3-C4 and C4-C5 levels (p < 0.01). The rest of the canal showed
significant differences between neutral-extension and flexion-extension at the C3
C4, C4-C5, C5-C6, and C6-C7 levels (p < 0.005). There were significant
differences between neutral-flexion at the C5-C6 and C6-C7 levels (p < 0.01).
Conclusions The occupancy of each structure in the cervical spine for each level
was revealed by this study. In addition, the dynamic changes in the cervical
spine with flexion and extension were seen to have different characteristics for
each level.
PMID- 26430595
TI - Inter- and Intraobserver Agreement of Morphological Grading for Central Lumbar
Spinal Stenosis on Magnetic Resonance Imaging.
AB - Study Design Validation study of a morphological grading system for central
lumbar spinal stenosis. Objective To evaluate and validate the inter- and
intraobserver agreement of a morphological grading system for central lumbar
spinal stenosis on magnetic resonance imaging between neurosurgeons and
radiologists. Methods Two neurosurgeons and two radiologists independently
assessed the morphological grading of lumbar spinal stenosis on pretreatment
magnetic resonance imaging of 84 patients. Inter- and intrarater agreements were
calculated by comparing the observers' evaluations level to level on the grading
method. The results of both clinicians were compared with the assessment of both
radiologists. Results On axial magnetic resonance images, 189 lumbar disk levels
were evaluated for the grade of stenosis. The interobserver agreement between the
clinicians was substantial. The interobserver agreement between clinician 1 and
both radiologists was substantial, and it was moderate between clinician 2 and
both radiologists. The clinicians' intraobserver agreement was almost perfect,
and the radiologists' intraobserver agreement was substantial. Conclusions The
interobserver agreement of this morphological grading for lumbar spinal stenosis
was high between both the clinicians and radiologists, whereas the intraobserver
agreement was almost perfect. Experienced clinicians may safely evaluate lumbar
magnetic resonance images using this morphological grading for central lumbar
spinal stenosis.
PMID- 26430596
TI - Utility of Computed Tomography following Anterior Cervical Diskectomy and Fusion.
AB - Study Design Retrospective case series. Objective To assess the utility of
postoperative computed tomography (CT) following anterior cervical diskectomy and
fusion (ACDF) and to determine the clinical circumstances most likely to lead to
an abnormal CT scan. Methods Patients who underwent ACDF at a tertiary center
over a span of 5 years were investigated. Only patients who had a minimum of 6
months' postoperative follow-up and a CT within 2 years after the surgery were
included in the study group. All the postoperative notes were reviewed to
determine indications for the CT, abnormalities identified, and whether the scan
led to an alteration in the treatment course. Results The charts of 690 patients
who underwent ACDF were reviewed. Of the 690 patients, 45 (7%) had postoperative
CTs. These patients accounted for 53 postoperative CT scans, 45 (85%) of which
were taken for patients who expressed persistent postoperative symptoms and/or
had abnormal imaging. There were no indications for 8 (15%) of the CTs. Patients
who had a CT for persistent symptoms and/or abnormal preliminary imaging were
significantly more likely to have an abnormal CT (p = 0.03) and/or an alteration
in treatment course (p = 0.04) compared with those with no symptomatic or
radiologic indication for CT. Conclusions CT is associated with minimal utility
regarding the alteration of treatment course when employed in asymptomatic
patients. Postoperative CT should be ordered solely for symptomatic patients or
those with other abnormal preliminary imaging. Judicious use of postoperative CT
will limit the radiation exposure and cost.
PMID- 26430597
TI - Factors Associated with Life Expectancy in Patients with Metastatic Spine Disease
from Adenocarcinoma of the Lung.
AB - Study Design Retrospective study. Objective Our objective was to identify
preoperative prognostic factors associated with survival in patients with spinal
metastasis from lung carcinoma. Methods A retrospective analysis of 26 patients
diagnosed with lung carcinoma metastatic to the spinal column was performed to
determine factors associated with survival. We used 3 months survival as the
clinical cutoff for whether surgical intervention should be performed. We
analyzed patients who survived less than 3 months compared with those who
survived more than 3 months. Demographic, preoperative, operative, and
postoperative factors including functional scores were collected for analysis.
Results The median survival for all patients in our study was 3.5 months. We
found a statistically significant difference between the group that survived less
than 3 months and the group that survived greater than 3 months in terms of
extrathoracic metastasis, visceral metastasis, and average postoperative modified
Rankin score. Conclusion Determining which patients with lung cancer spinal
metastases will benefit from surgical intervention is often dictated by the
patient's predicted life expectancy. Factors associated with poorer prognosis
include age, functional status, visceral metastases, and extrathoracic
metastases. Although the prognosis for patients with lung cancer spinal
metastases is poor, some patients may experience long-term benefit from surgical
intervention.
PMID- 26430599
TI - The Relationship between Preoperative Expectations and the Short-Term
Postoperative Satisfaction and Functional Outcome in Lumbar Spine Surgery: A
Systematic Review.
AB - Study Design Systematic review. Objective To examine the relationship between the
patient's preoperative expectations and short-term postoperative satisfaction and
functional outcome in lumbar spine surgery. Methods The Medline, Embase, and
Cochrane databases were queried using a predefined search algorithm to identify
all lumbar spine studies analyzing the influence of preoperative expectations on
postoperative satisfaction and functional outcome. Two independent reviewers and
a third independent mediator reviewed the literature and performed study
screening, selection, methodological assessment, and data extraction using an
objective protocol. Results Of 444 studies identified, 13 met the inclusion
criteria. Methodological quality scores ranged from 59 to 100% with the greatest
variability in defining patient characteristics and the methods of assessing
patient expectations. Patient expectations were assessed in 22 areas, most
frequently back and leg pain expectations and general expectations. Functional
outcome was assessed by 13 tools; the most common were the visual analog scale,
Oswestry Disability Index (ODI), and Short Form Health Survey (SF-36). Positive
expectations for symptomatology, activity, general health, and recovery
correlated with satisfaction. General expectations correlated with higher SF-36
Physical Subcomponent scores, better global function, and lower ODI outcome.
Conclusions on the influence of the expectations for pain were limited due to the
study heterogeneity, but the evidence suggests a positive correlation between the
expectation and outcome for back and leg pain. Conclusions Positive expectations
correlated significantly with short-term postoperative satisfaction and
functional outcome, including higher SF-36 scores, earlier return to work, and
decreased ODI scores. Future expectation-based investigations will benefit from
implementation of the standardized methods of expectation, satisfaction, and
outcome analysis discussed herein.
PMID- 26430598
TI - Intramedullary Spinal Cord Tumors: Part I-Epidemiology, Pathophysiology, and
Diagnosis.
AB - Study Design Broad narrative review. Objectives Intramedullary spinal cord tumors
(IMSCT) are rare neoplasms that can potentially lead to severe neurologic
deterioration, decreased function, poor quality of life, or death. As such, a
better understanding of these lesions is needed. The following article, part one
of a two-part series, addresses IMSCT with regards to their epidemiology,
histology, pathophysiology, imaging characteristics, and clinical manifestations.
Methods The authors performed an extensive review of the peer-reviewed literature
addressing the aforementioned objectives. Results Numerous IMSCT exist with
varying epidemiology. Each IMSCT has its own hallmark characteristics and may
vary with regards to how aggressively they invade the spinal cord. These lesions
are often difficult to detect and are often misdiagnosed. Furthermore,
radiographically and clinically, these lesions may be difficult to distinguish
from one another. Conclusions Awareness and understanding of IMSCT is imperative
to facilitate an early diagnosis and plan management.
PMID- 26430600
TI - Spontaneously Resolved Recurrent Cervical Epidural Hematoma in a 37-Week
Primigravida.
AB - Study Design Case report. Objective To describe a patient with a recurrent
spontaneous spinal epidural hematoma (SSEH) during pregnancy that had spontaneous
remission. Methods A 27-year-old primigravida at 37 weeks' gestation suddenly
felt a strong left shoulder pain without any trauma. She had a history of
fenestration for a spontaneous cervical hematoma when she was 18 years old. An
emergency magnetic resonance imaging revealed a recurrence of the cervical
epidural hematoma at the C4-T1 level, but she had no paralysis. Results The
patient subsequently underwent a cesarean section and delivered a healthy male
infant. Her spinal epidural hematoma disappeared. Multislice computed tomography
showed no evidence for a vascular malformation or tumor. Three years after the
initial cesarean section, she underwent a second one and delivered another male
infant. Conclusions We report on a rare case of recurrent SSEH during pregnancy
with no neurologic deficits that was treated nonoperatively with close
observation and resulted in spontaneous resolution. In such patients with no
neurologic deficits, nonoperative management with close observation may be a
reasonable alternative.
PMID- 26430601
TI - Sacroiliac Coalition: First Description and Report of a Successful Resection.
AB - Study Design Case report. Objective This report describes the first case of a
sacroiliac coalition, its clinical features, the diagnostic difficulties, and the
surgical treatment chosen in this case. Methods A 33-year-old man presented to
our outpatient clinics complaining of severe left-sided low back pain with an
intermitted nondermatomal radiation into the left thigh. The only abnormality on
a pelvic radiograph was a coin-size, faint hyperdensity, which was almost
overlooked. Subsequent computed tomography (CT) and magnetic resonance imaging
(MRI) confirmed two bridging bone spurs on the anterior surface of the left joint
with a fibrous interruption at the apex. After the conservative treatment failed,
a surgical treatment was offered to the patient. The coalition was resected via
an anterior retroperitoneal approach and through the tissue plane between the
psoas and the iliacus muscles. A histopathologic examination was performed and
confirmed the diagnosis of a coalition. Results The patient's pain resolved
immediately after surgery. After 8 months, a follow-up CT scan showed complete
removal of the coalition without any signs of recurrence, and at 12 months'
follow-up, the patient remained pain-free. Conclusions This is the first
published case of a sacroiliac coalition. The only sign of this rare condition on
the plain radiographs was very easy to miss. As has been discussed in the
literature, CT and MRI are important in the differential diagnostics of such
lesions. The histopathologic findings included that of a fibrous bar, confirming
the diagnosis, which is further corroborated by the complete resolution of the
symptoms.
PMID- 26430602
TI - Acute Spinal Subdural Hematoma after Vertebroplasty: A Case Report Emphasizing
the Possible Etiologic Role of Venous Congestion.
AB - Study Design Case report and literature review. Objective Spinal subdural
hematomas are rare events that often progress with severe neurologic deficits.
Although there have been several case reports in the literature of spontaneous
spinal subdural hematomas in the setting of anticoagulation, antiplatelet
therapy, or coagulation disorders, the exact pathophysiology of such phenomena
remains obscure. Methods We present the first report of a subdural hematoma after
a percutaneous vertebroplasty and provide a comprehensive review on the anatomy
of venous drainage of the vertebral bodies with emphasis on the possible effects
of venous congestion caused by cement obstruction. Results Because the subdural
hematoma occurred in the absence of major cement extravasation to the spinal
canal and two levels above the site of the vertebroplasty, we discuss the
possible role of venous congestion as the main etiologic factor leading to
rupture of the fragile, valveless radiculomedullary veins into the subdural
space. Conclusions The reported case supports a possible new pathophysiological
scheme for the development of spinal subdural hematoma in which venous congestion
plays a pivotal etiologic role. The reported findings suggests that future
anatomical and histologic studies investigating the response of the
radiculomedullary veins to congestive venous hypertension may shed new light into
the pathophysiology of spinal subdural hematomas.
PMID- 26430603
TI - Idiopathic Spinal Subarachnoid Hemorrhage: A Case Report and Review of the
Literature.
AB - Study Design Case report. Objective Spinal subarachnoid hemorrhage (SSAH) makes
up less than 1.5% of all the cases of subarachnoid hemorrhage. Most cases of
spontaneous SSAH occur in association with coagulopathy, lumbar punctures, or
minor trauma. Idiopathic SSAH is extremely rare with only 17 cases published.
Idiopathic SSAH presents a diagnostic dilemma, and the appropriate investigations
and treatment remain a matter of controversy. We report a case of idiopathic SSAH
and a review of the literature regarding its clinical presentation, diagnosis,
and treatment. Methods A 73-year-old woman presented to the emergency department
after spontaneously developing severe right leg and lower back pain while bending
over to vomit. After a review of the patient's history and examination, the
magnetic resonance imaging (MRI) of the thoracolumbar spine revealed T1
hyperintensity and T2 hypointensity, a diffusion-restricted collection at the T11
T12 level, and a posterior collection from L3 to S1 producing a mild displacement
of the thecal sac. Results The patient was taken for an L5 laminectomy.
Intraoperatively, rust-colored, xanthochromic fluid was drained from the
subarachnoid space, confirming SSAH. The thecal sac was decompressed. The
cultures and Gram stains were negative. Computer tomography (CT) and CT
angiography of the brain were normal. She recovered postoperatively with
resolution of the pain and no further episodes of hemorrhage after 2 years of
follow-up. Repeat thoracolumbar MRI, selective spinal angiogram, and six-vessel
cerebral angiogram did not reveal pathology. Conclusion We suggest a clinical
algorithm to aid in the diagnosis and management of such patients.
PMID- 26430604
TI - Spinal Metastases from a Primary Fallopian Tube Serous Adenocarcinoma: A Case
Report.
AB - Study Design Case report. Objective This case exemplifies the importance of a
high index of suspicion when dealing with intractable pain and neurologic
symptoms in patients with a history of cancer. Fallopian tube cancer is
relatively uncommon, accounting for less than 0.2% of all female malignancies.
Because of a low index of suspicion, it is often detected at an advanced stage.
From an orthopedic perspective, osseous metastasis from primary fallopian tube
malignancies is rare with only a few documented cases in the medical literature.
Methods This case report documents a 68-year-old woman who developed back pain
and leg weakness after undergoing surgical resection with adjuvant therapy of a
primary fallopian tube adenocarcinoma. Her hospital course and follow-up are
documented. Results Imaging revealed a compression fracture in the L1 vertebral
body that when a biopsy confirmed a soft tissue diagnosis of a high-grade serous
papillary adenocarcinoma of fallopian tube origin. The patient underwent a
surgical decompression, posterior stabilization, and tumor debulking with
postoperative resolution of her symptoms. Conclusions This is the first reported
case of a spine metastasis from a fallopian tube serous carcinoma in a living
patient. This case documents the diagnosis of a pathologic vertebral fracture due
to metastasis of an atypical cancer.
PMID- 26430605
TI - Sacral Stress Fracture Mimicking Lumbar Radiculopathy in a Mounted Police
Officer: Case Report and Literature Review.
AB - Study Design Case report and review of the literature. Objective To present a
unique case of L5 radiculopathy caused by a sacral stress fracture without
neurologic compression. Methods We present our case and its clinical evolution
and review the available literature on similar pathologies. Results Relief of the
unusual mechanical loading causing sacral stress fracture led to rapid resolution
of radiculopathy. Conclusion L5 radiculopathy can be caused by a sacral stress
fracture and can be relieved by simple mechanical treatment of the fracture.
PMID- 26430606
TI - Radiation-Induced Intraspinal Chondrosarcoma: A Case Report.
AB - Study Design Case report and review of the literature. Objective To report a
unique case of an intraspinal chondrosarcoma that was diagnosed 18 years after
radiotherapy for a cervical carcinoma and its remarkably unusual clinical
presentation. Methods A retrospective case description of an intraspinal mass
lesion that occurred 6 weeks after previous spinal surgery. Results Within ~9
weeks, the tumor had infiltrated the peritoneal cavity and reached the lumbar
subcutaneous tissue. Conclusion Radiation-induced sarcomas are rare, are highly
aggressive, and may be difficult to diagnose. Furthermore, the only means of
achieving long-term survival is through early and extensive surgery.
PMID- 26430607
TI - Dysphagia Secondary to Anterior Osteophytes of the Cervical Spine.
AB - Study Design Retrospective case series. Objective Diffuse idiopathic skeletal
hyperostosis (DISH) or Forestier disease involves hyperostosis of the spinal
column. Hyperostosis involving the anterior margin of the cervical vertebrae can
cause dysphonia, dyspnea, and/or dysphagia. However, the natural history
pertaining to the risk factors remain unknown. We present the surgical management
of two cases of dysphagia secondary to cervical hyperostosis and discuss the
etiology and management of DISH based on the literature review. Methods This is a
retrospective review of two patients with DISH and anterior cervical osteophytes.
We reviewed the preoperative and postoperative images and clinical history.
Results Two patients underwent anterior cervical osteophytectomies due to severe
dysphagia. At more than a year follow-up, both patients noted improvement in
swallowing as well as their associated pain. Conclusion The surgical removal of
cervical osteophytes can be highly successful in treating dysphagia if refractory
to prolonged conservative therapy.
PMID- 26430608
TI - Against the Odds: Massive Lumbar Intradural Disk Herniation in the Elderly.
AB - Study Design Case report. Objective Presentation of an unusual case of an elderly
patient with massive intradural disk herniation at the L2-L3 level. Methods
Clinical and imaging data are presented after obtaining informed consent from the
patient. Results A 90-year-old man suffering from sudden-onset neurogenic bladder
dysfunction and lower back pain but no further neurologic deficits initially
presented with magnetic resonance imaging and laboratory values suggestive of an
intraspinal infection. However, intraoperative inspection proved the unexpected
finding of a large intradural lumbar disk herniation at the L2-L3 level.
Conclusions Lumbar soft disk herniation to the intradural space is a rare event
and has never been described in a patient over the age of 75. This case of a 90
year-old man with acute-onset bladder dysfunction underlines the necessity to
consider this as a differential diagnosis in the case of a newly diagnosed
intradural mass.
PMID- 26430609
TI - Treatment of Hepatic Adenomatosis.
AB - Hepatic adenomatosis and hepatocellular adenomas share risk factors and the same
pathophysiologic spectrum. The presence in the liver of 10 hepatocellular
adenomas defines hepatic adenomatosis. The diagnosis may be established
incidentally during a liver radiologic examination in the asymptomatic patient,
or after associated right upper quadrant pain, hepatomegaly or liver test
abnormalities. Upon the diagnosis of hepatic adenomatosis or either of its life
threatening complications - hemorrhage and progression to hepatocellular
carcinoma - consideration should be given to potential medical, radiologic and
surgical interventions including: observation (estrogens and androgens
withdrawal), resection, transarterial embolization, radiofrequency ablation and
liver transplantation. The management of patients with hepatic adenomatosis can
be challenging. These patients should be ideally referred to centers with
expertise in the management of liver diseases.
PMID- 26430611
TI - Discrimination and Stigma.
PMID- 26430610
TI - Sleep in patients with schizophrenia.
AB - Numerous electrophysiological and neuroimaging studies have reported
neurophysiological and cognitive deficits in schizophrenia patients during
wakefulness. However, these findings have been inconsistently replicated across
different groups of patients, thus complicating the identification of underlying
neuronal defects. Sleep minimizes possible waking-related confounds, including
decreased motivation and presence of active symptoms. Additionally, the two main
sleep rhythms, slow waves and spindles, reflect the intrinsic activity of
corticothalamic circuits and are associated with cognitive activities, including
learning and memory, occurring during wakefulness. In this review I will present
the most relevant sleep findings in schizophrenia, with particular emphasis on
several recent studies that have consistently reported sleep spindle deficits in
patients with schizophrenia. I will then elaborate on how these findings may
contribute to a better understanding of the neurobiology of schizophrenia as well
as to the development of novel pharmacological and non-pharmacological
interventions to ameliorate the symptoms and cognitive impairments of
schizophrenia patients.
PMID- 26430612
TI - Experience of Late-Middle-Aged Women who Reside in Small and Medium-Sized Cities
in Becoming Psychologically Mature Women.
AB - OBJECTIVES: The purpose of this study is to search the inner world of
postmenopausal women in late-middle age who are facing senescence and live in
small and medium-sized cities. METHODS: The methods of the study were the
investigation and classification of answers to questions according to a
declarative ethnography analysis. The questions asked to late-middle-aged women
living in small and medium-sized cities were "How do you interpret and recognize
the changes in the body after menopause?" and "Which methods do you choose and
practice to maintain your health in relation to aging during middle age?".
RESULTS: Four positive topics and two negative topics were drawn from the study.
The four positive themes were: ambition; completion of a great mission; life with
a sense of affection; and gratitude for maintaining health. The negative themes
were: undulating emotion; and filling the emptiness. CONCLUSION: The recognition
of changes in the body after menopause in late-middle-aged women in small and
medium-sized cities can affect their preparation processes towards senescence. It
is critical to find the means to manage emergency health cases from early
adulthood to middle age, based on the outcomes of the study. The study also
emphasizes the importance of the woman's family's alternative strategies and
supportive systems, which can fit into the cultural context of the community.
PMID- 26430613
TI - The Use of Task-based Cognitive Tests for Defining Vocational Aptness of
Individuals with Disabilities.
AB - OBJECTIVES: The purpose of this study was to demonstrate the use of task-based
cognitive tests to detect potential problems in the assessment of work training
for vocational rehabilitation. METHODS: Eleven participants with a normal range
of cognitive functioning scores were recruited for this study. Participants were
all trainees who participated in a vocational training program. The Rey Complex
Figure Test and the Allen Cognitive Level Screen were randomly administered to
all participants. Responses to the tests were qualitatively analyzed with matrix
and scatter charts. RESULTS: Observational outcomes derived from the tests
indicated that response errors, distortions, and behavioral problems occurred in
most participants. These factors may impede occupational performance despite
normal cognitive function. These findings suggest that the use of task-based
tests may be beneficial for detecting potential problems associated with the work
performance of people with disabilities. CONCLUSION: Specific analysis using the
task-based tests may be necessary to complete the decision-making process for
vocational aptness. Furthermore, testing should be led by professionals with a
higher specialization in this field.
PMID- 26430614
TI - A Study on the Characteristics of Infrequent and Frequent Outpatients Visiting
Korean Traditional Medical Facilities.
AB - OBJECTIVES: This study was intended to analyze the characteristics of infrequent
and frequent outpatients visiting Korean medical facilities, and find the related
variables of frequent users. METHODS: The data source was the Report on the Usage
and Consumption of Korean Medicine (2011) published by the Ministry of Health and
Welfare and Korea Institute for Health and Social Affairs. We analyzed outpatient
data using SAS 9.2. RESULTS: As much as 46.6% of the patients used Korean medical
services over 11 times in 3 months. The proportion of frequent users increased
depending on age, and their proportion was high in the low-income and low
education group. People with musculoskeletal disease, stroke, hypertension, and
obesity were more likely to use Korean medical services. In general, patients
were satisfied with their treatment, with frequent outpatients being more
satisfied than infrequent outpatients. In logistic regression analysis, age and
musculoskeletal disease were significant determinants of frequency of use of
Korean medical services. CONCLUSION: Age, musculoskeletal disease, and specific
diseases were highly associated with frequent Korean medical utilization.
PMID- 26430615
TI - Modification of AxSYM Human Immunodeficiency Virus Assay to Identify Recent Human
Immunodeficiency Virus Infections in Korean Human Immunodeficiency Virus-Positive
Individuals.
AB - OBJECTIVES: To estimate human immunodeficiency virus (HIV) incidence using HIV
avidity assays in Korea, we established a serological testing method to
differentiate recent HIV infections from long-standing ones. METHODS: We adopted
two incidence assays, the BED HIV-1 incidence test (Calypte Biomedical) and an
HIV avidity assay (using Abbott AxSYM HIV Antigen/Antibody Combo), and performed
them on Korean HIV samples obtained from 81 HIV seroconverters (n = 193), 135 HIV
positive samples, and three HIV commercial incidence panels (PRB965, PRB933, and
PRB601 from SeaCare). To determine the most optimal concentration of the
chaotropic agent (Guanidine) and the cutoff value for the avidity assay, we
evaluated the sensitivity and specificity of the assay at different concentration
levels. RESULTS: We determined that the concentration of Guanidine to be used in
the avidity assay was 1.5M. The cutoff value of the avidity index (AI) was 0.8,
and the sensitivity and specificity were 90.2% and 83.8%, respectively, under
this condition. The gray zone for the avidity assay was 0.75-0.85 AI. The mean of
coefficient of variation was low, at 5.43%. CONCLUSION: An optimized avidity
assay for the diagnosis of recent HIV infections using Korean samples was
established. This assay will be applied to investigate the level of recent
infection and will provide basic data to the HIV prevention policy in Korea.
PMID- 26430616
TI - Identifying Barriers to Human Immunodeficiency Virus Testing for Men Who Have Sex
with Men in South Korea.
AB - OBJECTIVES: The principal objective of this study was to identify the barriers to
testing for men who have sex with men (MSM) in Korea, something that might prove
useful in future studies of this nature. METHODS: This study was conducted at gay
bars nationwide in Korea. After considering several offline locations (gay bars)
where MSM candidates are commonly located, random recruitment was performed using
time-location sampling. A total of 944 individuals participated in this survey. A
total sample of 921 cases (23 cases were excluded) was used for analysis. A self
administered questionnaire measuring the individuals' demographics, human
immunodeficiency virus (HIV)/AIDS knowledge, stigma, phobia, optimism bias, self
efficacy for condom use, and sexual practices was used. RESULTS: About 61.8% (N =
569) of respondents reported having been tested at least once in their lifetime,
and 38.9% (N = 358) acknowledged being tested within the past 12 months. After
adjusting for age, education, and number of partners in a logistic regression
analysis, awareness of testing place [odds ratio (OR) = 4.04], exposure to HIV
prevention campaign (1.54), fear (OR = 1.13), and discrimination toward people
with HIV/AIDS (OR = 0.94) were the main factors associated with HIV testing.
CONCLUSION: To accomplish widespread HIV testing for Korean MSM, the
accessibility of testing centers and advertisement of voluntary counseling and
testing to MSM are needed.
PMID- 26430618
TI - Joint Disease Mapping of Two Digestive Cancers in Golestan Province, Iran Using a
Shared Component Model.
AB - OBJECTIVES: Recent studies have suggested the occurrence patterns and related
diet factor of esophagus cancer (EC) and gastric cancer (GC). Incidence of these
cancers was mapped either in general and stratified by sex. The aim of this study
was to model the geographical variation in incidence of these two related cancers
jointly to explore the relative importance of an intended risk factor, diet low
in fruit and vegetable intake, in Golestan, Iran. METHODS: Data on the incidence
of EC and GC between 2004 and 2008 were extracted from Golestan Research Center
of Gastroenterology and Hepatology, Hamadan, Iran. These data were registered as
new observations in 11 counties of the province yearly. The Bayesian shared
component model was used to analyze the spatial variation of incidence rates
jointly and in this study we analyzed the data using this model. Joint modeling
improved the precision of estimations of underlying diseases pattern, and thus
strengthened the relevant results. RESULTS: From 2004 to 2008, the joint
incidence rates of the two cancers studied were relatively high (0.8-1.2) in the
Golestan area. The general map showed that the northern part of the province was
at higher risk than the other parts. Thus the component representing diet low in
fruit and vegetable intake had larger effect of EC and GC incidence rates in this
part. This incidence risk pattern was retained for female but for male was a
little different. CONCLUSION: Using a shared component model for joint modeling
of incidence rates leads to more precise estimates, so the common risk factor, a
diet low in fruit and vegetables, is important in this area and needs more
attention in the allocation and delivery of public health policies.
PMID- 26430617
TI - High Prevalence of AmpC beta-Lactamases in Clinical Isolates of Escherichia coli
in Ilam, Iran.
AB - OBJECTIVES: Widespread use of beta-lactam antibiotics could cause resistance to
this group of antibiotics in pathogenic bacteria through the production of the
enzyme beta-lactamases. The aim of this study is to determine the molecular
detection of AmpC beta-lactamases among clinical Escherichia coli isolated from
Ilam hospitals in Ilam, Iran. METHODS: One hundred and twelve clinical isolates
of E. coli were collected from hospitalized patients and were identified by
biochemical tests. They were evaluated for extended spectrum beta-lactamases
(ESBLs) production, and the positive strains were subjected to AmpC enzymes; for
detection of AmpC cluster genes, multiplex polymerase chain reaction was applied.
RESULTS: The analysis showed 62.5% of isolates were ESBLs positive and that five
strains revealed the AmpC cluster genes. This is the first report of FOXM cluster
genes in E. coli in Iran. CONCLUSION: Based on our results, the prevalence of
AmpC beta-lactamases is increasing in Iran, which caused failure in antibiotic
therapy. So, the current study recommended the revision of antibiotic policy in
Iranian hospitals.
PMID- 26430619
TI - Korea Community Health Survey Data Profiles.
AB - In 2008, Korea Centers for Disease Control and Prevention initiated the first
nationwide survey, Korea Community Health Survey (KCHS), to provide data that
could be used to plan, implement, monitor, and evaluate community health
promotion and disease prevention programs. This community-based cross-sectional
survey has been conducted by 253 community health centers, 35 community
universities, and 1500 interviewers. The KCHS standardized questionnaire was
developed jointly by the Korea Centers for Disease Control and Prevention staff,
a working group of health indicators standardization subcommittee, and 16
metropolitan cities and provinces with 253 regional sites. The questionnaire
covers a variety of topics related to health behaviors and prevention, which is
used to assess the prevalence of personal health practices and behaviors related
to the leading causes of disease, including smoking, alcohol use, drinking and
driving, high blood pressure control, physical activity, weight control, quality
of life (European Quality of Life-5 Dimensions, European Quality of Life-Visual
Analogue Scale, Korean Instrumental Activities of Daily Living ), medical
service, accident, injury, etc. The KCHS was administered by trained
interviewers, and the quality control of the KCHS was improved by the
introduction of a computer-assisted personal interview in 2010. The KCHS data
allow a direct comparison of the differences of health issues among provinces.
Furthermore, the provinces can use these data for their own cost-effective health
interventions to improve health promotion and disease prevention. For users and
researchers throughout the world, microdata (in the form of SAS files) and
analytic guidelines can be downloaded from the KCHS website
(http://KCHS.cdc.go.kr/) in Korean.
PMID- 26430620
TI - The History and Future of Plastic and Reconstructive Surgery.
PMID- 26430621
TI - How You Become Who You Are: A New Concept of Beauty for Plastic Surgery.
PMID- 26430622
TI - Development of Facial Rejuvenation Procedures: Thirty Years of Clinical
Experience with Face Lifts.
AB - Facial rejuvenation procedures can be roughly divided into face lift surgery and
nonoperative, less invasive procedures, such as fat grafts, fillers, botulinum
toxin injections, thread lifts, or laserbrasion. Face lift surgery or
rhytidectomy is the procedure most directly associated with rejuvenation, due to
its fundamental ability to restore the anatomical changes caused by aging.
Various methods of face lift surgery have been developed over the last hundred
years, thanks to advances in the understanding of facial anatomy and the
mechanisms of aging, as well as the dedication of innovative surgeons. However,
no generally applicable standard method exists, because the condition of each
patient is different, and each operative method has advantages and disadvantages.
Specific characteristics of the skin of Asians and their skeletal anatomy should
be considered when determining the operative method to be used on Asian patients.
Plastic surgeons should improve their ability to analyze the original aesthetic
properties and problem areas of each patient, drawing on scientific knowledge
about the aging process, and they should develop the skills necessary to perform
various rejuvenative techniques. In the present article, we reviewed various face
lift procedures and the current methods of modified double plane face lift, based
on our clinical experience of over 30 years.
PMID- 26430624
TI - Comparative Analysis of the Extracellular Matrix Composition in Proliferating and
Involuted Infantile Hemangiomas.
AB - BACKGROUND: Changes in the composition of the extracellular matrix (ECM) occur
between the proliferating and involuted phases of infantile hemangiomas (IH), and
are associated with angiogenic growth. We examined the composition of the ECM in
proliferating and involuted IHs and assessed correlations between the composition
of the ECM and whether the IH was in the proliferating or the involuted phase.
METHODS: We evaluated IH samples from a cohort of patients who had five
proliferating IHs and five involuted IHs. The following ECM molecules were
analyzed using enzyme-linked immunosorbent assays and immunohistochemistry:
laminin, fibronectin, collagen type I, collagen type II, and collagen type III.
RESULTS: The involuted IHs had higher levels of deposition of collagen type III
than the proliferating IHs. The median values (interquartile ranges) were 1.135
(0.946-1.486) and 1.008 (0.780-1.166) (P=0.019), respectively. The level of
laminin was higher in involuted IHs than in proliferating IHs, with median values
(interquartile ranges) of 3.191 (2.945-3.191) and 2.479 (1.699-3.284) (P=0.047),
respectively. Abundant collagen type III staining was found in involuted IHs.
Laminin alpha4 chain staining was clearly present within the basement membrane
adjacent to the blood vessels, and was significantly more intense in involuted
IHs than in proliferative IHs. CONCLUSIONS: Involuted hemangiomas showed
extensive deposition of collagen III and laminin, suggesting that differences in
the composition of the ECM reflect stages of the development of IHs. This pattern
may be due to the rapid senescence of IHs.
PMID- 26430623
TI - Capsular Contracture after Breast Augmentation: An Update for Clinical Practice.
AB - Capsular contracture is the most common complication following implant based
breast surgery and is one of the most common reasons for reoperation. Therefore,
it is important to try and understand why this happens, and what can be done to
reduce its incidence. A literature search using the MEDLINE database was
conducted including search terms 'capsular contracture breast augmentation',
'capsular contracture pathogenesis', 'capsular contracture incidence', and
'capsular contracture management', which yielded 82 results which met inclusion
criteria. Capsular contracture is caused by an excessive fibrotic reaction to a
foreign body (the implant) and has an overall incidence of 10.6%. Risk factors
that were identified included the use of smooth (vs. textured) implants, a
subglandular (vs. submuscular) placement, use of a silicone (vs. saline) filled
implant and previous radiotherapy to the breast. The standard management of
capsular contracture is surgical via a capsulectomy or capsulotomy. Medical
treatment using the off-label leukotriene receptor antagonist Zafirlukast has
been reported to reduce severity and help prevent capsular contracture from
forming, as has the use of acellular dermal matrices, botox and neopocket
formation. However, nearly all therapeutic approaches are associated with a
significant rate of recurrence. Capsular contracture is a multifactorial fibrotic
process the precise cause of which is still unknown. The incidence of contracture
developing is lower with the use of textured implants, submuscular placement and
the use of polyurethane coated implants. Symptomatic capsular contracture is
usually managed surgically, however recent research has focussed on preventing
capsular contracture from occurring, or treating it with autologous fat transfer.
PMID- 26430625
TI - Clinical Experience of the Klippel-Trenaunay Syndrome.
AB - BACKGROUND: The Klippel-Trenaunay syndrome (KTS) is characterized by three
clinical features, namely cutaneous capillary malformations, venous
malformations, and soft tissue and/or bony hypertrophy of the extremities. The
varied manifestations are attributed to the unpredictable clinical nature and
prognosis of the syndrome. To elucidate the clinical characteristics of this
disease, we reviewed a relatively large number of KTS patients who presented to
our vascular anomalies center. METHODS: We conducted a retrospective study with
19 patients who were diagnosed with KTS and treated in our vascular anomalies
clinic between 2003 and 2014, and examined their demographic characteristics,
their clinical features, and the treatments administered. RESULTS: The sex
distribution was balanced, with 9 (47%) males and 10 (53%) females. The mean
follow-up period was 4.1 years (range, 7 months-9 years). Most of the patients
received conservative treatments such as medication or physiotherapy. Compression
therapies such as wearing of elastic garments/bandages were also administered,
and surgical interventions were considered only when the patients became
excessively symptomatic. Other treatments included laser therapy and
sclerotherapy, and all the treatments were adjusted according to each case,
tailored to the conditions of the individual patients. CONCLUSIONS: KTS is an
extremely rare, multifactorial disorder that induces widely varied symptoms.
Because of this unique feature, plastic surgeons, when not careful, tend to
attach a one-sided importance to typical symptoms such as limb hypertrophy or
capillary malformation and thus overlook other symptoms and clinical features.
KTS can be suspected in all infants who show capillary malformations or limb
hypertrophy and require a multi-disciplinary approach for comprehensive
management.
PMID- 26430626
TI - The 50 Most Cited Papers in Craniofacial Anomalies and Craniofacial Surgery.
AB - BACKGROUND: Citation analysis is a recognized scientometric method of classifying
cited articles according to the frequency of which they have been referenced. The
total number of citations an article receives is considered to reflect it's
significance among it's peers. METHODS: Until now, a bibliometric analysis has
never been performed in the specialty of craniofacial anomalies and craniofacial
surgery. This citation analysis generates an extensive list of the 50 most
influential papers in this developing field. Journals specializing in
craniofacial surgery, maxillofacial surgery, plastic surgery, neurosurgery,
genetics and pediatrics were searched to demonstrate which articles have
cultivated the specialty within the past 55 years. RESULTS: The results show an
intriguing compilation of papers which outline the fundamental knowledge of
craniofacial anomalies and the developments of surgical techniques to manage
these patients. CONCLUSIONS: This citation analysis provides a summation of the
current most popular trends in craniofacial literature. These esteemed papers aid
to direct our decision making today within this specialty.
PMID- 26430627
TI - Effects of Bariatric Surgery on Facial Features.
AB - BACKGROUND: Bariatric surgeries performed in the USA has increased twelve-fold in
the past two decades. The effects of rapid weight loss on facial features has not
been previously studied. We hypothesized that bariatric surgery will mimic the
effects of aging thus giving the patient an older and less attractive appearance.
METHODS: Consecutive patients were enrolled from the bariatric surgical clinic at
our institution. Pre and post weight loss photographs were taken and used to
generate two surveys. The surveys were distributed through social media to assess
the difference between the preoperative and postoperative facial photos, in terms
of patients' perceived age and overall attractiveness. 102 respondents completed
the first survey and 95 respondents completed the second survey. RESULTS: Of the
14 patients, five showed statistically significant change in perceived age (three
more likely to be perceived older and two less likely to be perceived older). The
patients were assessed to be more attractive postoperatively, which showed
statistical significance. CONCLUSIONS: Weight loss does affect facial aesthetics.
Mild weight loss is perceived by survey respondents to give the appearance of a
younger but less attractive patient, while substantial weight loss is perceived
to give the appearance of an older but more attractive patient.
PMID- 26430628
TI - A Multicenter Noncomparative Clinical Study on Midface Rejuvenation Using a
Nonabsorbable Polypropylene Mesh: Evaluation of Efficacy and Safety.
AB - BACKGROUND: Facial rejuvenation can be achieved using a variety of techniques.
Since minimally invasive procedures for face lifting have become popular because
of their convenience and short operating time, numerous minimally invasive
surgical procedures have been developed. In this study, a nonabsorbable
polypropylene mesh is introduced as a new face lifting instrument, with the
nasolabial fold as the main target area. In this paper, we report the efficacy
and safety of a polypropylene mesh in midface rejuvenation. METHODS: Thirty-three
subjects with moderate-to-severe nasolabial folds were enrolled from two medical
institutions for a noncomparative single-sample study. A mesh was inserted above
the superficial muscular aponeurotic system layer, reaching the nasolabial folds
through a temporal scalp incision. After 3 weeks, the temporal end of the mesh
was pulled to provide a lifting effect. Then, the mesh was fixed to the deep
temporal fascia using nonabsorbable sutures. To evaluate efficacy, we compared
the scores on the Wrinkle Severity Rating Scale and a visual analog scale for
patient satisfaction between the baseline and 7 weeks postoperatively. In
addition, we evaluated safety based on the incidence of adverse events. RESULTS:
The treatment was deemed effective at improving wrinkles in 23 of 28 cases, and
patient satisfaction improved significantly during the study period. There were
seven cases of skin or subcutaneous tissue complications, including edema and
erythema, but there were no suspected serious adverse events. CONCLUSIONS: Face
lifting using a nonabsorbable mesh can improve nasolabial folds without serious
adverse effects. Thus, this technique is safe and effective for midface
rejuvenation.
PMID- 26430630
TI - Radiation Therapy Following Total Keloidectomy: A Retrospective Study over 11
Years.
AB - BACKGROUND: Radiotherapy treatment after keloidectomy is known to be an effective
method for reducing the rate of recurrence. However, to date, the appropriate
total radiation dose and fractionation have not yet been confirmed. The authors
performed a retrospective analysis to identify the appropriate radiation dose and
fractionation in post-keloidectomy radiotherapy. METHODS: From May 2000 to
February 2011, postoperative radiotherapy was performed on 39 lesions in 28
patients after total keloidectomy. The keloid lesions were confined to the ear
lobes. Between May 2000 and May 2004, 14 keloids were treated with surgical
excision, followed by a total radiation dose of 1,200 cGy in three fractions over
four to five days (group 1). Between June 2004 to February 2011, 25 keloids were
treated with surgical excision, followed by a total radiation dose of 1,500 cGy
in three fractions over four to five days (group 2). Patients were given a survey
asking them to report their experiences regarding reoperation, recurrence of
symptoms, recurrence of the lesion, and satisfaction with the operation. RESULTS:
Of the 28 patients who were treated, 20 underwent follow-up. Group 2 had more
cases showing elevation with erythematous changes, whereas group 1 had more cases
showing progressive stages of elevation than group 2. These differences were
statistically significant. Moreover, a correlation was observed between the level
of keloid elevation and the extent of symptoms. CONCLUSIONS: We suggest 1,500 cGy
of radiation in three fractions following keloidectomy for ear lobe keloids. A
further randomized study is needed to assess the recurrence of keloids after
radiotherapy.
PMID- 26430629
TI - Lateral Brow Lift: A Multi-Point Suture Fixation Technique.
AB - BACKGROUND: Descent of the lateral aspect of the brow is one of the earliest
signs of aging. The purpose of this study was to describe an open surgical
technique for lateral brow lifts, with the goal of achieving reliable,
predictable, and long-lasting results. METHODS: An incision was made behind and
parallel to the temporal hairline, and then extended deeper through the
temporoparietal fascia to the level of the deep temporal fascia. Dissection was
continued anteriorly on the surface of the deep temporal fascia and
subperiosteally beyond the temporal crest, to the level of the superolateral
orbital rim. Fixation of the lateral brow and tightening of the orbicularis oculi
muscle was achieved with the placement of sutures that secured the tissue
directly to the galea aponeurotica on the lateral aspect of the incision. An
additional fixation was made between the temporoparietal fascia and the deep
temporal fascia, as well as between the temporoparietal fascia and the galea
aponeurotica. The excess skin in the temporal area was excised and the incision
was closed. RESULTS: A total of 519 patients were included in the study.
Satisfactory lateral brow elevation was obtained in most of the patients
(94.41%). The following complications were observed: total relapse (n=8), partial
relapse (n=21), neurapraxia of the frontal branch of the facial nerve (n=5), and
limited alopecia in the temporal incision (n=9). CONCLUSIONS: We consider this
approach to be a safe and effective procedure, with long-lasting results.
PMID- 26430631
TI - Scar Wars: Preferences in Breast Surgery.
AB - BACKGROUND: The uptake of breast reconstruction is ever increasing with
procedures ranging from implant-based reconstructions to complex free tissue
transfer. Little emphasis is placed on scarring when counseling patients yet they
remain a significant source of morbidity and litigation. The aim of this study
was to examine the scarring preferences of men and women in breast oncoplastic
and reconstructive surgery. METHODS: Five hundred men and women were asked to
fill out a four-page questionnaire in two large Irish centres. They were asked
about their opinions on scarring post breast surgery and were also asked to rank
the common scarring patterns in wide local excisions, oncoplastic procedures,
breast reconstructions as well as donor sites. RESULTS: Fifty-eight percent of
those surveyed did not feel scars were important post breast cancer surgery. 61%
said that their partners' opinion of scars were important. The most preferred
wide local excision scar was the lower lateral quadrant scar whilst the scars
from the deep inferior epigastric artery perforator (DIEP) flap were most
favoured. The superior gluteal artery perforator flap had the most preferred
donor site while surprisingly, the DIEP had the least favourite donor site.
CONCLUSIONS: Scars are often overlooked when planning breast surgery yet the
extent and position of the scar needs to be outlined to patients and it should
play an important role in selecting a breast reconstruction option. This study
highlights the need for further evaluation of patients' opinions regarding scar
patterns.
PMID- 26430632
TI - Nipple-Areola Complex Necrosis after Nipple-Sparing Mastectomy with Immediate
Autologous Breast Reconstruction.
AB - BACKGROUND: Autologous or implant-based breast reconstruction after nipple
sparing mastectomy is increasingly preferred worldwide as a breast cancer
treatment option. However, postoperative nipple-areola complex (NAC) necrosis is
the most significant complication of nipple-sparing mastectomy. The purpose of
our study was to identify the risk factors for NAC necrosis, and to describe the
use of our skin-banking technique as a solution. METHODS: We reviewed cases of
immediate autologous breast reconstruction after nipple-sparing mastectomy at our
institution between June 2005 and January 2014. The patients' data were reviewed
and the risk of NAC necrosis was analyzed based on correlations between patient
variables and NAC necrosis. Moreover, data pertaining to five high-risk patients
who underwent the donor skin-banking procedure were included in the analysis.
RESULTS: Eighty-five patients underwent immediate autologous breast
reconstruction after nipple-sparing mastectomy during the study period. Partial
or total NAC necrosis occurred in 36 patients (43.4%). Univariate analysis and
binary regression modeling found that body mass index, smoking history, radiation
therapy, and mastectomy volume were significantly associated with NAC necrosis.
Of the 36 cases of NAC necrosis, 31 were resolved with dressing changes,
debridement, or skin grafting. The other five high-risk patients underwent our
prophylactic skin-banking technique during breast reconstruction surgery.
CONCLUSIONS: NAC necrosis is common in patients with multiple risk factors. The
use of the skin-banking technique in immediate autologous breast reconstruction
is an attractive option for high-risk patients. Banked skin can be used in such
cases without requiring additional donor tissue, with good results in terms of
aesthetic and reconstructive outcomes.
PMID- 26430633
TI - Comparison of Clinical and Functional Outcomes Using Pectoralis Major and
Cutaneous Free Flaps for Hypopharyngeal Squamous Cell Carcinoma.
AB - BACKGROUND: The purpose of this study was to compare postoperative morbidities
and functional outcomes of pectoralis major myocutaneous (PMMC) flap and
cutaneous free flap reconstruction approaches in hypopharyngeal squamous cell
carcinoma patients. METHODS: We retrospectively reviewed records from 99 patients
who underwent hypopharyngeal reconstruction with a cutaneous free flap (n=85) or
PMMC flap (n=14) between 1995 and 2013. Morbidity was classified into
hospitalization, medical, or flap-related complications. Functional outcomes were
classified into oral re-alimentation and decannulation time. RESULTS: The overall
flap-related complication rate was higher in the PMMC flap group (n=8, 57.1%;
P=0.019), but the medical morbidity rate was higher in the cutaneous free flap
group (n=68, 80%; P=0.006). The rate of pneumonia was higher in the cutaneous
free flap group (n=48, 56.5%; P=0.020). Pulmonary premorbidity was the variable
most significantly associated with pneumonia (odds ratio=3.012, P=0.012). There
was no statistically significant difference in oral re-alimentation and
decannulation time between the two groups. CONCLUSIONS: Although the functional
superiority of free flaps has been reported in many studies, our results do not
support this hypothesis. One limitation of our study is the relatively smaller
flap size and fewer PMMC flap cases compared with the cutaneous free flap group.
The low postoperative medical morbidity incidence rate in the PMMC flap group was
clinically significant; however, the free flap group had more flap-related
complications. Thus, PMMC flaps should be considered a viable option, especially
for patients with pulmonary premorbidities.
PMID- 26430634
TI - Short-Term Strength Deficit Following Zone 1 Replantations.
AB - BACKGROUND: Hand strength deficit following digital replantation is usually
attributed to the mechanical deficiency of the replanted digit. Zone 1
replantation, however, should not be associated with any mechanical deficit, as
the joint and tendon are intact. We evaluate short-term motor functions in
patients who have undergone single-digit zone 1 replantation. METHODS: A single
institution retrospective review was performed for all patients who underwent
zone 1 replantation. Hand and pinch strengths were evaluated using standard
dynamometers. Each set of measurements was pooled according to follow-up periods
(within 1 month, 1 to 2 months, 2 to 3 months, and after 3 months). The uninjured
hand was used as reference for measurements. RESULTS: The review identified 53
patients who had undergone zone 1 replantation and presented for follow-up
visits. Compared to the uninjured hand, dynamometer measurements revealed
significantly less strength for the hand with replanted digit at one month. The
relative mean grip, pulp, and key pinch strength were 31%, 46%, and 48% of the
uninjured hand. These three strength measurements gradually increased, with
relative strength measurements of 59%, 70%, and 78% for 4-month follow up.
CONCLUSIONS: Despite the lack of joint or tendon injury, strength of the injured
hand was significantly lower than that of the uninjured hand during the 4 months
following replantation. Improved rehabilitation strategies are needed to diminish
the short-term negative impact that an isolated zone 1 replantation has on the
overall hand strength.
PMID- 26430635
TI - Reconstruction of Ankle and Heel Defects with Peroneal Artery Perforator-Based
Pedicled Flaps.
AB - BACKGROUND: The reconstruction of ankle and heel defects remains a significant
problem for plastic surgeons. The following options exist for reconstructing such
defects: local random flaps, reverse flow island flaps, and free flaps. However,
each of these methods has certain drawbacks. Peroneal artery perforators have
many advantages; in particular, they are predictable and reliable for ankle and
heel reconstructions. In this study, we report our clinical experience with
peroneal artery perforator-based pedicled flaps in ankle and heel
reconstructions. METHODS: From July 2005 to October 2012, 12 patients underwent
the reconstruction of soft tissue defects in the ankle and heel using a peroneal
artery perforator-based pedicled flap. These 12 cases were classified according
to the anatomical area involved. The cause of the wound, comorbidities, flap
size, operative results, and complications were analyzed through retrospective
chart review. RESULTS: The mean age of the patients was 52.4 years. The size of
the flaps ranged from 5*4 to 20*8 cm(2). The defects were classified into two
groups based on whether they occurred in the Achilles tendon (n=9) or heel pad
(n=3). In all 12 patients, complete flap survival was achieved without
significant complications; however, two patients experienced minor wound
dehiscence. Nevertheless, these wounds healed in response to subsequent
debridement and conservative management. No patient had any functional deficits
of the lower extremities. CONCLUSIONS: Peroneal artery perforator-based pedicled
flaps were found to be a useful option for the reconstruction of soft tissue
defects of the ankle and heel.
PMID- 26430636
TI - Optical Biopsy of Peripheral Nerve Using Confocal Laser Endomicroscopy: A New
Tool for Nerve Surgeons?
AB - Peripheral nerve injuries remain a challenge for reconstructive surgeons with
many patients obtaining suboptimal results. Understanding the level of injury is
imperative for successful repair. Current methods for distinguishing healthy from
damaged nerve are time consuming and possess limited efficacy. Confocal laser
endomicroscopy (CLE) is an emerging optical biopsy technology that enables
dynamic, high resolution, sub-surface imaging of live tissue. Porcine sciatic
nerve was either left undamaged or briefly clamped to simulate injury. Diluted
fluorescein was applied topically to the nerve. CLE imaging was performed by
direct contact of the probe with nerve tissue. Images representative of both
damaged and undamaged nerve fibers were collected and compared to routine H&E
histology. Optical biopsy of undamaged nerve revealed bands of longitudinal nerve
fibers, distinct from surrounding adipose and connective tissue. When damaged,
these bands appear truncated and terminate in blebs of opacity. H&E staining
revealed similar features in damaged nerve fibers. These results prompt
development of a protocol for imaging peripheral nerves intraoperatively. To this
end, improving surgeons' ability to understand the level of injury through real
time imaging will allow for faster and more informed operative decisions than the
current standard permits.
PMID- 26430637
TI - Treatment of Pseudoangiomatous Stromal Hyperplasia of the Breast: Implant-Based
Reconstruction with a Vascularized Dermal Sling.
AB - Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign
mesenchymal lesion with incidental histologic findings. Surgical excision is
recommended as the treatment of choice for PASH, although the recurrence rates
after excision range from 15% to 22%. A 46-year-old-female presented with a six
month history of bilateral breast enlargement and painful sensation mimicking
inflammatory carcinoma. Imaging studies demonstrated innumerable enhancing
nodules in both breasts. Due to the growth of the lesions and progressive
clinical symptoms, bilateral subcutaneous mastectomy was performed. Grossly, the
specimens were round and well-circumscribed, and the histologic examination
revealed PASH. After mastectomy, we created a pocket with the pectoralis major
muscle and a lower skin flap, which was deepithelized. Anatomical mammary
implants were inserted, and the nipple areolar complex was transferred to a new
position as a free graft. The aesthetic result was satisfactory after twelve
months of follow-up.
PMID- 26430638
TI - Letter: A Consideration of Breast Imagery in Art as Depicted through Western
Painting.
PMID- 26430639
TI - Response to Letter: A Consideration of Breast Imagery in Art as Depicted through
Western Painting.
PMID- 26430641
TI - Isolated Congenital Nasal Bifid Septum Separated by a Wide Layer of Soft Tissue.
PMID- 26430640
TI - Nasal Reconstruction of a Frontonasal Dysplasia Deformity Using Aesthetic
Rhinoplasty Techniques.
PMID- 26430642
TI - Capsular Contracture after Calf Augmentation with Silicone Implant Insertion.
PMID- 26430643
TI - The Modified Trap Door Flap for Reconstruction of Posterior Pinna and Concha
Defects.
PMID- 26430644
TI - The Oblique Rectus Abdominis Musculocutaneous Flap for Reconstruction after
Resection of a Spermatic Cord Liposarcoma.
PMID- 26430645
TI - Technical Considerations to Avoid Microvascular Complications during Groin Lymph
Node Free Flap Transfer.
PMID- 26430646
TI - Breakthrough Technique for Free Tissue Transfer of Poorly Vascularized Lower
Extremity: Arteriovenous Loop Revisited.
PMID- 26430647
TI - Segmental Hemihyperplasia-Related Macrodactyly with Congenital Renal Agenesis: A
Hand Surgeon's Point of View.
PMID- 26430649
TI - Solitary Gluteus Maximus Muscle Metastasis in a Breast Cancer Patient.
PMID- 26430648
TI - Median Nerve Compression by the Feeding Vessels of a Large Arteriovenous
Malformation in the Axilla.
PMID- 26430650
TI - Endoscopic Excision of Osteochondroma of the Mandibular Angle.
PMID- 26430651
TI - Langerhans Cell Histiocytosis with Frontal Bone Indentation by an Adjoining
Primary Soft Tissue Lesion in a 17-Month-Old Asian Male Child.
PMID- 26430652
TI - Lymphoepithelioma-like Carcinoma of the Skin in the Cheek with a Malignant
Metastatic Cervical Lymph Node.
PMID- 26430653
TI - Cosmetic Surgery: Is It Science or Art?
PMID- 26430654
TI - The early outcome of single-incision versus multi-port laparoscopic
cholecystectomy.
AB - BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is a newly
developed method of performing cholecystectomy and has been increasingly used.
The aim of this study is to see if SILC has any advantages over conventional
(three-port) laparoscopic cholecystectomy (CLC). MATERIALS AND METHODS: In this
cross-sectional study, 52 patients who underwent SILC (group A) during the period
from May 2011 to March 2013 were compared with 62 patients who underwent CLC
(group B) at two centers affiliated to Shiraz University of Medical Sciences in
Shiraz, Iran. Data were gathered on operation time, pre- and postoperative
complications, patients' postoperative pain, pain reliever use, duration of
hospital stay, and return to work, and these data were compared using SPSS
software version 16. RESULTS: The mean age of patients was 38.01 +/- 13.24 in
group A and 44.82 +/- 15.11 in group B. Mean body mass index (BMI) was 23.97 +/-
4.78 and 26.22 +/- 4.67 in groups A and B, respectively. The mean operation time
was 76.4 +/- 29.0 min in group A and 72.9 +/- 24.1 min in group B (P = 0.496).
Preoperative complications were 3.8% in group A and 0 in group B (P = 0.206).
Postoperative complications were 17.3% in group A and 11.3% in group B (P =
0.423). The mean for early postoperative pain revealed no significant difference
(P = 0.814), but the mean pain on discharge was significantly higher in group A
patients (P = 0.034). Regarding the mean admission time and return to normal
activity, we found no significant differences. CONCLUSION: SILC does not have any
special advantages over CLC with regard to surgical outcomes, but it can be a
safe alternative to CLC, especially in patients concerned about cosmoses.
PMID- 26430655
TI - Pure gonadal dysgenesis (46 XX type) with a familial pattern.
AB - 46, XX gonadal dysgenesis without the phenotype of Turner's syndrome is described
as "pure". Although, previous investigations obtained that commonly gonadal
dysgenesis did not cause breast development as a result of low levels of
circulating estradiol. However, in this study, we aimed to report a familial pure
gonadal dysgenesis with and without normal secondary sexual characteristics. In
this study, we reported three siblings with pure gonadal dysgenesis with and
without normal secondary sexual characteristics. The elder two sisters had a
normal female phenotype and the youngest had amenorrhea with no breast
development (B1) and pubic hair. In addition, it seems that the absence of pubic
hair occurred due to delayed constitutional puberty. According to results, it
seems that clinicians should consider different presentations for pure gonadal
dysgenesis with familial pattern.
PMID- 26430656
TI - Placental expression of D6 decoy receptor in preeclampsia.
AB - OBJECTIVE: The purpose of this study was to investigate the expression of the D6
decoy receptor that can bind chemokines and target them for degradation,
resulting in inhibition of inflammation in placentas from preeclamptic and normal
pregnancies. METHODS: The current study was carried out in 35 pregnant women (23
patients with preeclampsia and 12 healthy, normotensive pregnant women) during
the third trimester of pregnancy. The expressions of D6 decoy receptor in the
placenta were determined with real time reverse transcriptase polymerase chain
reaction and western blotting. RESULTS: The mRNA and protein of D6 decoy receptor
were detected in all of placentas from preeclamptic and normal pregnancies.
Placental D6 decoy receptor mRNA expression was significantly lower in patients
with preeclampsia than in patients with normal pregnancies. Western blot analyses
revealed decreased protein expression in cases of preeclampsia. CONCLUSION: The
expression of the D6 decoy receptor in preeclamptic placentas was significantly
lower than in normal placentas. Further studies are needed to clarify the
underlying mechanisms that link decreased expression of placental D6 decoy
receptor and preeclampsia.
PMID- 26430657
TI - Performance of Momguard, a new non-invasive prenatal testing protocol developed
in Korea.
AB - OBJECTIVE: To evaluate the performance of Momguard, non-invasive prenatal test
(NIPT) for detecting trisomy (T) 21, T18, T13, and sex-chromosome abnormalities
recently developed in Korea. METHODS: This preliminary study formed part of a
large prospective cohort study conducted at Asan Medical Center, Seoul, Korea.
Only pregnant women who underwent both NIPT and confirmatory karyotyping were
included in this study. NIPT results were compared with those of karyotype
analyses. RESULTS: Among 93 eligible cases, NIPT results could not be obtained in
one case due to a low fetal cell-free DNA fraction. Based on NIPT, eight cases of
fetal aneuploidies, including T21 (n=5), T18 (n=2), and T13 (n=1), were
identified. For T21 and T18, the sensitivity and specificity of NIPT were both
100%, with a false-positive and false-negative rate of 0% and a positive
predictive value of 100%. One patient classified as having intermediate risk for
T13 by NIPT was confirmed to have T13 by karyotyping, and there were no false
negative cases. No cases of sex-chromosome anomalies were detected by NIPT or
karyotyping during the study period. CONCLUSION: Momguard is a reliable screening
tool for detecting T21 and T18. For T13 and sex-chromosome anomalies, further
prospective studies are necessary to confirm its utility.
PMID- 26430658
TI - Risk of cesarean section after induced versus spontaneous labor at term
gestation.
AB - OBJECTIVE: To investigate whether the cesarean section (CS) rate is increased in
women whose labor was induced compared to those who had spontaneous labor at term
pregnancy. METHODS: A retrospective study was performed in women whose labor was
either induced (induction group, n=497) or spontaneous (spontaneous group, n=878)
at 37+0 to 41+6 weeks of gestation from January 2008 to June 2009. Maternal age,
parity, body mass index (BMI), Bishop scores, gestational age, hypertension,
diabetes, delivery mode, indications for CS, neonatal outcome were compared
between the two groups. Multiple logistic regression analysis was used to examine
the association between the CS rate and labor induction after adjusting for
potential confounding variables. RESULTS: CS (17.3% vs. 5.3%, P<0.001) and vacuum
assisted delivery (10.7% vs. 6.4%, P<0.001) rates were significantly higher in
the induction group compared to the spontaneous group. The CS rate in the
induction group was higher than the spontaneous group not only in nulliparous
women (25.3% vs. 8.6%, P<0.001), but also in multiparous women (3.8% vs. 0.3%,
P=0.002). However, after adjusting confounding factors, the higher CS rate was
significantly associated with advanced maternal age, higher BMI, lower Bishop
scores and nulliparity, with no demonstrable tie to labor induction. Neonatal
outcome in the two groups were comparable. CONCLUSION: Although CS rate was
higher in women whose labor was induced than those who had spontaneous labor,
this higher rate was associated with maternal age, BMI, Bishop scores and parity,
but was not impacted by labor induction per se.
PMID- 26430659
TI - Correlation between postpartum depression and premenstrual dysphoric disorder:
Single center study.
AB - OBJECTIVE: To describe the prevalence and correlates of the postpartum depression
and premenstrual dysphoric disorder. METHODS: One hundred sixty six women were
assessed around 10th to 14th days after delivery in Gangneung Asan Hospital,
Korea, from September 2011 to March 2012. We checked their risk factors for
postpartum depressive disorders using the Beck Depression Inventory and the
Edinburgh Postnatal Depression Scale. Premenstrual dysphoric disorder was
evaluated retrospectively and was defined as having more than 5 of the following
10 symptoms: breast tenderness, bloating, headache, peripheral edema (hand and
foot), depressive symptoms, anger, irritability, anxiety, oversensitivity, and
exaggerated mood swings. RESULTS: The prevalence rate of postpartum depression
using the Edinburgh Postnatal Depression Scale >=10 and Beck Depression Inventory
>=10 was 13.9% (23/166). We found statistical differences (P<0.01) between the
postpartum depression group and the postpartum non-depression group in smoking
history, past history of psychiatric problems, and level of marital satisfaction.
The prevalence rate of premenstrual syndrome (PMS) was 9% (15/166) and among 23
women in the postpartum depression group, eight were determined to have
premenstrual dysphoric disorder, yielding a prevalence rate of 34.8% (8/23).
Among 143 women in the postpartum non-depression group, seven were determined to
have PMS, yielding a prevalence rate of 4.9% (7/143). A correlation between
postpartum depression and PMS was thus found (P<0.01). CONCLUSION: PMS appears to
be associated with postpartum depression. This means that a hormone-related
etiology appears to be one risk factor for postpartum depression.
PMID- 26430660
TI - Preoperative hypoalbuminemia is a risk factor for 30-day morbidity after
gynecological malignancy surgery.
AB - OBJECTIVE: To determine the relationship between preoperative hypoalbuminemia and
the development of complications after gynecological cancer surgery, as well as
postoperative bowel function and hospital stay. METHODS: The medical records of
533 patients with gynecological cancer surgery at Konkuk University Hospital
between 2005 and 2013 were reviewed. Serum albumin level <3.5 g/dL was defined as
hypoalbuminemia. All perioperative complications within 30-days after surgery,
time to resumption of normal diet and length of postoperative hospital stay, were
analyzed. Regression models were used to assess predictors of postoperative
morbidity. RESULTS: The median age was 49 years (range, 13 to 85 years). Eighty
patients (15%) had hypoalbuminemia. Hypoalbuminemic patients had significantly
higher consumption of alcohol >2 standard drinks per day, lower American Society
of Anesthesiologist score, higher frequency of ascites, and more advanced stage
compared with non-hypoalbuminemic patients. Overall complication rate within 30
days after surgery was 20.3% (108 out of 533). Hypoalbuminemic patients were more
likely to develop postoperative complications compared to non-hypoalbuminemic
patients (34.3% vs. 17.8%, P=0.022), and had significantly longer median time to
resumption of normal diet (3.3 [1-6] vs. 2.8 [0-15] days, P=0.005) and length of
postoperative hospital stay (0 [7-50] vs. 9 [1-97] days, P=0.014). In
multivariate analysis, age >50 (odds ratio [OR], 2.478; 95% confidence interval
[CI], 1.310 to 4.686; P=0.005), operation time (OR, 1.006; 95% CI, 1.002 to
1.009; P=0.006), and hypoalbuminemia (OR, 2.367; 95% CI, 1.021 to 5.487; P=0.044)
were the significant risk factor for postoperative complications. CONCLUSION:
Preoperative hypoalbuminemia in patients with elective surgery for gynecologic
malignancy is an independent predictor of 30-days postoperative complications.
Identification of this subset and preoperative optimization of nutritional status
may improve surgical outcomes.
PMID- 26430661
TI - The prognostic value of squamous cell carcinoma antigen for predicting tumor
recurrence in cervical squamous cell carcinoma patients.
AB - OBJECTIVE: The aim of this study was to evaluate the prognostic value of squamous
cell carcinoma antigen (SCC-Ag) and the optimal cut-off value for predicting
recurrence in cervical squamous cell carcinoma patients with complete remission
after primary treatment. METHODS: We reviewed the records of 783 cervical
squamous cell cancer patients who underwent primary therapy and showed complete
remission at our institution between January 2000 and April 2014. A receiver
operating characteristic curve was used to determine the optimal SCC-Ag threshold
to predict recurrence. Cox regression model for disease free survival was used to
assess differences in outcome. RESULTS: The median follow-up period was 41.2
months, and 154 patients (19.7%) had recurrent disease. The median pretreatment
and posttreatment SCC-Ag level was 2.6 ng/mL (range, 0.1 to 532.0 ng/mL) and 0.7
ng/mL (range, 0.0 to 46.8 ng/mL), respectively. Both pretreatment and
posttreatment SCC-Ag levels were higher in the recurrence group (P=0.017 and
P=0.039). Optimal cut-off value of pretreatment and posttreatment SCC-Ag for
predicting recurrence was 1.86 ng/mL (area under the curve, 0.663; P=0.000), and
0.9 ng/mL (area under the curve, 0.581; P=0.002), respectively. In the
multivariate Cox regression model, pretreatment SCC-Ag >1.86 ng/mL (odds ratio,
2.11; 95% confidence interval, 1.38 to 3.22; P=0.001) and posttreatment SCC-Ag
>0.9 ng/mL (odds ratio, 1.64; 95% confidence interval, 1.18 to 2.28; P=0.003)
were significantly associated with poor disease free survival. CONCLUSION:
Patients with pretreatment SCC-Ag >1.86 ng/mL or posttreatment SCC-Ag >0.9 ng/mL
should be considered at high risk for cancer recurrence after complete remission,
and therefore, closer surveillance is needed.
PMID- 26430663
TI - Prediction of lymph node metastasis in patients with apparent early endometrial
cancer.
AB - OBJECTIVE: The purpose of this study is to investigate the incidence of lymph
node metastasis in early endometrial cancer patients and to evaluate preoperative
clinicopathological factors predicting lymph node metastasis. METHODS: We
identified 142 patients with endometrial cancer between January 2000 and February
2013. All patients demonstrated endometrioid adenocarcinoma with grade 1 or 2 on
preoperative endometrial biopsy. Preoperative magnetic resonance imaging showed
that tumors were confined to the uterine corpus with superficial myometrial
invasion (less than 50%), and there were no lymph nodes enlargements. All
patients had complete staging procedures and were surgically staged according to
the 2009 FIGO (International Federation of Gynecology and Obstetrics) staging
system. Clinical and pathological data were obtained from medical records and
statistically analyzed. RESULTS: Of the 142 patients, 127 patients (89.4%)
presented with stage 1A, 8 (5.6%) with stage IB, 3 (2.1%) with stage II, and 4
(2.8%) with stage III disease. Three patients (2.1%) had lymph node metastasis-2
IIIC1 and 1 IIIC2 disease. Age, preoperative tumor grade, and myometrial invasion
less than 50% on preoperative MRI were not associated with lymph node metastasis.
A high preoperative serum CA-125 level (>35 IU/mL) was a statistically
significant factor for predicting lymph node metastasis on univariate and
multivariate analyses. Lymph node metastasis was only found in patients with
preoperative grade 2 tumors or a high serum CA-125 level. CONCLUSION:
Preoperative tumor grade and serum CA-125 level can predict lymph node metastasis
in apparent early endometrial cancer patients.
PMID- 26430662
TI - Learning curve analysis of laparoscopic radical hysterectomy for gynecologic
oncologists without open counterpart experience.
AB - OBJECTIVE: To evaluate the learning curve of laparoscopic radical hysterectomy
(LRH) for gynecologic oncologists who underwent residency- and fellowship
training on laparoscopic surgery without previous experience in performing
abdominal radical hysterectomy (ARH). METHODS: We retrospectively reviewed 84
patients with FIGO (International Federation of Gynecology and Obstetrics) stage
IB cervical cancer who underwent LRH (Piver type III) between April 2006 and
March 2014. The patients were divided into two groups (surgeon A group, 42
patients; surgeon B group, 42 patients) according to the surgeon with or without
ARH experience. Clinico-pathologic data were analyzed between the 2 groups.
Operating times were analyzed using the cumulative sum technique. RESULTS: The
operating time in surgeon A started at 5 to 10 standard deviations of mean
operating time and afterward steeply decreased with operative experience (Pearson
correlation coefficient=-0.508, P=0.001). Surgeon B, however, showed a gentle
slope of learning curve within 2 standard deviations of mean operating time
(Pearson correlation coefficient=-0.225, P=0.152). Approximately 18 cases for
both surgeons were required to achieve surgical proficiency for LRH. Multivariate
analysis showed that tumor size (>4 cm) was significantly associated with
increased operating time (P=0.027; odds ratio, 4.667; 95% confidence interval,
1.187 to 18.352). CONCLUSION: After completing the residency- and fellowship
training course on gynecologic laparoscopy, gynecologic oncologists, even without
ARH experience, might reach an acceptable level of surgical proficiency in LRH
after approximately 20 cases and showed a gentle slope of learning curve, taking
less effort to initially perform LRH.
PMID- 26430665
TI - Efficacy and safety of a 24-day regimen of drospirenone-containing combined oral
contraceptive in Korean women.
AB - This study assesses the efficacy and safety of a 24-day regimen of drospirenone
containing combined oral contraceptive, and demonstrates that it is an effective
and safe option for contraception, releasing symptom of premenstrual dysphoric
disorder and acne in Korean women.
PMID- 26430664
TI - Expression of angiogenic factors in cryopreserved mouse ovaries after heterotopic
autotransplantation.
AB - OBJECTIVE: Revascularization is critical for successful ovarian tissue
transplantation. Vascular endothelial growth factor (VEGF) and angiopoietin-2
(angpt-2) are the principal mediators of neovascularization. This study was
designed to assess VEGF and angpt-2 levels in cryopreserved ovarian tissue after
heterotopic autotransplantation. METHODS: Ovarian tissues harvested from ICR mice
at 5 to 6 weeks of age were stratified as follows: no cryopreservation (controls,
group I); vitrification in VFS-40 (vitrification, group II); and gradual freezing
in dimethyl sulfoxide (slow-freezing, group III). Frozen specimens were thawed at
room temperature, assaying VEGF and angpt-2 levels 1 week after cryopreservation
and 2 weeks after autotransplantation. RESULTS: VEGF and angpt-2 protein levels
were significantly lower in cryopreserved ovaries of groups II and III than in
controls (group I, P<0.05), whereas groups II and III did not differ
significantly in this regard. After autotransplantation of cryopreserved ovarian
tissue, VEGF and angpt-2 protein levels did not differ significantly by technique
but tended to be lower than corresponding levels in controls. CONCLUSION:
Expression of angiogenic factors in ovarian tissue is thought to vary by method
of cryopreservation. Our findings indicate that levels of angiogenic factors
expressed in cryopreserved ovarian tissue after autotransplantation do not differ
appreciably from control levels, regardless of cryopreservation technique.
PMID- 26430666
TI - Hybrid laparoscopic myomectomy: A novel technique.
AB - The objective of this study was to report on a new surgical technique, hybrid
laparoscopic myomectomy that integrates the advantages of transumbilical
laparoendoscopic single-site surgery and those of isobaric laparoscopy, and the
initial experience with 14 cases. All of the procedures were performed by a
single surgeon who has over 18 years of experience in laparoscopic surgery and 4
years of experience in laparoendoscopic single-site surgery. All cases of hybrid
laparoscopic myomectomy were completed safely and effectively without conversion
to conventional laparoscopic procedure. The median operative time was 75 minutes
(range, 30 to 100 minutes). No postoperative complication was observed. The
findings show that hybrid laparoscopic myomectomy is a safe and feasible surgical
technique, and therefore can be a feasible, minimally invasive alternative to
either abdominal or laparoendoscopic single-site surgery myomectomy.
PMID- 26430667
TI - Prenatal diagnosis of congenital mesoblastic nephroma.
AB - Congenital mesoblastic nephroma is a rare renal tumor that is diagnosed during
pregnancy and is associated with polyhydramnios, prematurity, and neonatal
hypertension. Differential diagnoses include Wilms tumor, adrenal neuroblastoma,
and other abdominal tumors. We report a case of congenital mesoblastic nephroma
detected by prenatal ultrasonography as a large fetal renal mass with
polyhydramnios at 32 weeks of gestation. Ultrasonography showed a 6*6-cm complex,
solid, hyperechoic, round mass in the right kidney. At 35 weeks of gestation, the
patient was admitted with preterm premature rupture of membranes and the baby was
delivered vaginally. Postnatal ultrasonography and computed tomography showed a
heterogeneous solid mass on the right kidney. At the end of the first week of
life, a right nephrectomy was performed and subsequent pathological examination
confirmed a cellular variant of congenital mesoblastic nephroma with a high
mitotic count. Postoperative adjuvant chemotherapy was administered. The newborn
was discharged in good condition.
PMID- 26430668
TI - Successful pregnancy outcome in a Korean patient with symptomatic Wilson's
disease.
AB - Wilson's disease is an inherited disease of copper metabolism leading to the
toxic accumulation of copper, primarily in the liver and brain. Although the
literature shows successful outcomes after proper treatment, pregnant patients
with Wilson's disease still need close monitoring and management. Here, we report
the case of a successful pregnancy in a Korean woman with Wilson's disease. A 33
year-old primigravid patient with Wilson's disease visited our antenatal clinic.
Of her own volition, she had stopped her medication 2 years earlier. Oral zinc
oxide therapy was started, and she was closely monitored throughout her
pregnancy. She delivered a healthy female infant weighing 3.13 kg through a
cesarean section. After delivery, the clinical course of both the mother and the
baby were uneventful. We review crucial points in the treatment and the
management dilemmas raised by the patient.
PMID- 26430669
TI - Intrapelvic dissemination of early low-grade endometrioid stromal sarcoma due to
electronic morcellation.
AB - Endometrioid stromal sarcoma is a rare malignancy that originates from
mesenchymal cells. It is classified into low-grade endometrioid stromal sarcoma
(LGESS) and high-grade endometrioid stromal sarcoma. Ultrasonographic findings of
LGESS resemble those of submucosal myomas, leading to the possible preoperative
misdiagnosis of LGESS as uterine leiomyoma. Electronic morcellation during
laparoscopic surgery in women with LGESS can result in iatrogenic intraabdominal
dissemination and a poorer prognosis. Here, we report a patient with LGESS who
underwent a supracervical hysterectomy and electronic morcellation for a presumed
myoma in another hospital. Disseminated metastatic lesions of LGESS in the
posterior cul-de-sac and rectal serosal surface were absent on primary surgery,
but found during reexploration. In conclusion, when LGESS is found incidentally
following previous morcellation during laparoscopic surgery for presumed benign
uterine disease, we highly recommend surgical reexploration, even when there is
no evidence of a metastatic lesion in imaging studies.
PMID- 26430670
TI - Successful delivery after conservative resectoscopic surgery in a patient with a
uterine tumor resembling ovarian sex cord tumor with myometrial invasion.
AB - Uterine tumor resembling ovarian sex cord tumors (UTROSCT) is an extremely rare
type of uterine stromal neoplasm that exhibits prominent sex cord-like
differentiation. The clinical characteristics of a UTROSCT are not fully
understood. Most reported cases of UTROSCT were treated by hysterectomy with or
without bilateral salpingo-oophorectomy; however, a few cases have been treated
by only tumor resection in patients who had a strong desire to preserve their
fertility. We present a case of UTROSCT with myometrial invasion, which resulted
in a successful delivery after the patient was treated by resectoscopic surgery
and conservation of the uterus, and a brief review of the literature.
PMID- 26430671
TI - Adult granulosa cell tumor presenting with massive ascites, elevated CA-125
level, and low (18)F-fluorodeoxyglucose uptake on positron emission
tomography/computed tomography.
AB - Adult granulosa cell tumors (AGCTs) presenting with massive ascites and elevated
serum CA-125 levels have rarely been described in the literature. An ovarian
mass, massive ascites, and elevated serum CA-125 levels in postmenopausal women
generally suggest a malignant ovarian tumor, particularly advanced epithelial
ovarian cancer. AGCT has low (18)F-fluorodeoxyglucose uptake on positron emission
tomography/computed tomography due to its low metabolic activity. In the present
report, we describe a case of an AGCT with massive ascites, elevated serum CA-125
level, and low (18)F-fluorodeoxyglucose uptake on positron emission
tomography/computed tomography.
PMID- 26430672
TI - Massive hemoperitoneum due to a ruptured corpus luteum cyst in a patient with
congenital hypofibrinogenemia.
AB - Congenital afibrinogenemia/hypofibrinogenemia is a rare inherited hematologic
disorder in which a patient lacks or has insufficient level of fibrinogen, the
blood coagulation factor I. The incidence of this uncommon disease is 1 to 2 per
1 million individuals. Hence, massive hemoperitoneum caused by ovulation in a
woman with congenital afibrogenemia is also a very rare clinical condition.
Massive hemoperitoneum usually presents as acute abdominal pain with potential
findings of peritonitis including abdominal distention, hypotension and
tachycardia with critical consequences. We performed emergent endoscopic surgery
for hemoperitoneum caused by a ruptured corpus luteum cyst in a patient with
congenital hypofibrinogenemia. To the best of our knowledge, this was the first
case report of such treatment in Korea.
PMID- 26430673
TI - Laparoscopic uterine artery occlusion before cervical curettage in cervical
ectopic pregnancy: Safe and effective for preventing massive bleeding.
AB - Cervical ectopic pregnancy is associated with high risk for massive bleeding
conditions. Cervical ectopic pregnancy can usually be treated by methotrexate
injection or surgery. We present 4 cases of cervical ectopic pregnancy that were
treated successfully with different uterine-conserving methods. By comparing our
experience of 4 cases managed in different ways, we found that laparoscopic
uterine artery occlusion before cervical curettage is more effective method for
preventing massive bleeding.
PMID- 26430674
TI - Current status of infrastructures of obstetrics and gynecology in South Korea.
PMID- 26430676
TI - Determining the level of awareness of the physicians in using the variety of
electronic information resources and the effecting factors.
AB - BACKGROUND: Understanding of the medical society's from the types of information
resources for quick and easy access to information is an imperative task in
medical researches and management of the treatment. The present study was aimed
to determine the level of awareness of the physicians in using various electronic
information resources and the factors affecting it. MATERIALS AND METHODS: This
study was a descriptive survey. The data collection tool was a researcher-made
questionnaire. The study population included all the physicians and specialty
physicians of the teaching hospitals affiliated to Isfahan University of Medical
Sciences and numbered 350. The sample size based on Morgan's formula was set at
180. The content validity of the tool was confirmed by the library and
information professionals and the reliability was 95%. Descriptive statistics
were used including the SPSS software version 19. RESULTS: On reviewing the need
of the physicians to obtain the information on several occasions, the need for
information in conducting the researches was reported by the maximum number of
physicians (91.9%) and the usage of information resources, especially the
electronic resources, formed 65.4% as the highest rate with regard to meeting the
information needs of the physicians. Among the electronic information databases,
the maximum awareness was related to Medline with 86.5%. Among the various
electronic information resources, the highest awareness (43.3%) was related to
the E-journals. The highest usage (36%) was also from the same source. The
studied physicians considered the most effective deterrent in the use of
electronic information resources as being too busy and lack of time. CONCLUSION:
Despite the importance of electronic information resources for the physician's
community, there was no comprehensive knowledge of these resources. This can lead
to less usage of these resources. Therefore, careful planning is necessary in the
hospital libraries in order to introduce the facilities and full capabilities of
the mentioned resources and methods of information retrieval.
PMID- 26430677
TI - Applying and comparing empirical and full Bayesian models in study of evaluating
relative risk of suicide among counties of Ilam province.
AB - INTRODUCTION: Disease mapping includes a set of statistical techniques that
provides maps based on estimates of diseases rates. Bayesian ones are the most
important models in this field. They consider prior information on changes in the
disease rates in overall map and spatial pattern of the disease. These include a
broad range of models with their own formulation, characteristics, strengths, and
weaknesses. In the present study, we explain and compare three important and
widely-used Bayesian models in the study of evaluating relative risk of suicide
in Ilam province. MATERIALS AND METHODS: In this applied-ecological research,
suicide incidence in Ilam province in 2008 and 2009 was analyzed by use of Gamma
Poisson, Log-normal, and BYM Bayesian models. Models were fitted to data using
WinBUGS software. RESULTS: Fitting the three models showed that Darehshahr and
Shirvan-Chrdavol had the highest and the lowest relative risk of suicide,
respectively (relative risks based on Gamma-Poisson, Log-normal, and BYM models
were 2.243, 2.275, and 2.279 for Dareshahr and 0.321, 0.321, and 0.319 for
Shirvan-Chrdavol, respectively). CONCLUSION: Despite some differences in
estimates, the ranks of relative risks in counties in all three models are the
same. The counties based on the relative risks of suicide from the most to the
least are: Darehshahr, Ilam, Dehloran, Eyvan, Abdanan, Mehran, Malekshahi, and
Shirvan-Chrdavol.
PMID- 26430678
TI - The effect of educational intervention on health promoting lifestyle: Focusing on
middle-aged women.
AB - BACKGROUND: Lifestyle affects people's health and life length, however, no
sufficient studies have been done on the effect of lifestyle on middle-ageing, as
the transitional period from adulthood to old-ageing, this study has been
conducted to study the effect of educational intervention on health promoting
lifestyle of middle-aged women in Lenjan city of Isfahan Province, Iran. METHODS:
This quasi-experimental study was conducted on 88 middle-aged women were selected
through randomized sampling from two health centers in Lenjan, and then were
categorized into experimental and control groups. To collect data, a researcher
made demographic and life style questionnaire was used. The educational
intervention was performed in five sessions. Data were collected from both groups
in two stages: Before the intervention and 3 months after the education. Data
were analyzed with using SPSS-20 and P < 0.05 were considered statistically
significant. RESULTS: The results showed that educational program had a positive
significant effect on increasing the mean scores in the intervention group,
considering the physical activity, mental health, and interpersonal relationship,
P < 0.001. However, regarding the nutrition, the mean increase was not
significant (P = 0.113). CONCLUSION: According to the findings, it is evident
that educational intervention is beneficial for various aspects of middle-aged
women's lifestyle. Therefore, applying a healthy lifestyle seems essential for
having a healthy aging period, and educational intervention can be effective.
PMID- 26430675
TI - Experimental Models of Microvascular Immunopathology: The Example of Cerebral
Malaria.
AB - Human cerebral malaria is a severe and often lethal complication of Plasmodium
falciparum infection. Complex host and parasite interactions should the precise
mechanisms involved in the onset of this neuropathology. Adhesion of parasitised
red blood cells and host cells to endothelial cells lead to profound endothelial
alterations that trigger immunopathological changes, varying degrees of brain
oedema and can compromise cerebral blood flow, cause cranial nerve dysfunction
and hypoxia. Study of the cerebral pathology in human patients is limited to
clinical and genetic field studies in endemic areas, thus cerebral malaria (CM)
research relies heavily on experimental models. The availability of malaria
models allows study from the inoculation of Plasmodium to the onset of disease
and permit invasive experiments. Here, we discuss some aspects of our current
understanding of CM, the experimental models available and some important recent
findings extrapolated from these models.
PMID- 26430679
TI - Learning challenges of nursing students in clinical environments: A qualitative
study in Iran.
AB - BACKGROUND: Clinical learning environment is a complex social entity. This
environment is effective on the learning process of nursing students in the
clinical area. However, learning in clinical environment has several benefits,
but it can be challenging, unpredictable, stressful, and constantly changing. In
attention to clinical experiences and factors contributing to the learning of
these experiences can waste a great deal of time and energy, impose heavy
financial burden on educational systems, cause mental, familial and educational
problems for students, and compromise the quality of patient care. Therefore,
this study was carried out with the goal of determining the learning challenges
of nursing students in clinical environments in Iran. MATERIALS AND METHODS: In
this qualitative study carried out in 2012-2013, 18 undergraduate nursing
students were selected by using purposive sampling method from the Faculty of
Nursing and Midwifery of Tehran and Shahid Beheshti Universities. Semi-structured
interviews were used to collect data. The content analysis method was used to
determine relevant themes. RESULTS: Two themes were derived from the data
analysis, which represented the students' clinical learning challenges. These two
themes included insufficient qualification of nursing instructors and
unsupportive learning environment. CONCLUSIONS: Identification of the students'
clinical learning challenges and actions to remove or modify them will create
more learning opportunities for the students, improve the achievement of
educational goals, provide training to nursing students with the needed
competencies to meet the complex demands of caring and for application of
theories in practice, and improve the quality of healthcare services.
PMID- 26430680
TI - The Effect of nutrition education on knowledge, attitude, and performance about
junk food consumption among students of female primary schools.
AB - BACKGROUND: Undoubtedly, proper nutrition has important role in safeguarding the
individual from many diseases, especially chronic ones, and increasing ones
physical and intellectual efficiency. Considering the importance of nutrition
education to school-age kids, this research was done with the purpose of
determining the effect of nutrition education on the knowledge, attitude, and
performance of female students at primary school about junk food consumption.
MATERIALS AND METHODS: This is an experimental intervention study in Shahr-e-kord
city about the reduction of junk foods consumption in 2011. Seventy-two primary
girl students were randomly divided into 2 groups, experimental (36) and controls
(36). Before of the educational program, self-administrative questionnaire and
FFQ (Food Frequency Questionnaire) questionnaire were filled out for both the
groups. The self-administrative questionnaire was completed 3 times (before,
immediately, and 2 months after education), and FFQ questionnaire was completed 2
times (before and 2 months after education) by students. After pre-test, 4
educational session classes in experimental group were performed. Finally, data
were collected and analyzed by SPSS 16 computer software. RESULTS: Demographic
variables of the studied population in 2 groups were similar. Before
intervention, there were no significant differences regarding the knowledge,
attitude, and performance in 2 groups (P > 0/05). After intervention, there were
significant differences in the levels of knowledge, attitude, and performance
between experimental and control groups (P < 0.001). CONCLUSION: According to the
results, intervention has positive impact on pattern of nutrition, and it can be
concluded that intervention is effective on increasing or improving the
knowledge, attitude, and performance of the students.
PMID- 26430681
TI - Investigating selected patient safety indicators using medical records data.
AB - INTRODUCTION: Medical errors in hospitals kill more people every year than AIDS,
breast cancer and auto accidents combined. Widespread consensus exists that
health care organizations can reduce patient injuries by improving the
environment for safety from implementing different alternatives from technical
and managerial improvements to considering medical record data. Considering the
preventability of medical errors, the Agency for Healthcare Quality and Research
(AHRQ) developed patient safety indicators (PSIs). This study analyzes the PSIs
calculated in Alzahra Hospital of Isfahan. MATERIALS AND METHODS: This study was
conducted retrospectively using the inpatient medical record data of hospitalized
patients in a six month period, from October 2010 to March 2011. An experienced
team in the fields of medical record, health management and health information
technology was involved in data reviewing. Based on a prior consultation and
reviewing, some PSIs were selected. Indicators were calculated considering AHRQ
guidelines. Excel software and hospital information system software were used.
RESULTS: Across all studied medical records of patients, out of 25,164
discharges, below measures were calculated. -8 Foreign Body cases (PSI 5) (0.31
per 1000). -30 Postoperative Hemorrhage or Hematoma cases (PS I9) (2.2 per 1000).
-5 Accidental Puncture or Laceration cases (PSI 15) (0.3 per1000). -8
Complications of Anesthesia cases (PSI 1) (2.2 per 1000). -96 Selected Infections
Due to Medical Care cases (PSI 7) (3.8 per1000). -17 cases of Postoperative Wound
Dehiscence (PSI 14) (3.7per1000). -1 Birth Trauma - Injury to Neonate case, and
(PSI 17) (1.7 per 1000). - 18 Obstetric Trauma - Cesarean Delivery cases (PSI 20)
(40 per 1000) were flagged by studied PSIs developed by AHRQ. CONCLUSION:
Comparing with the reported rates by other studies and AHRQ study in 2006, all of
calculated indicators have inadequate condition; i.e. these are far from
empirical estimated rates. The hospital administrators should be more sensitive
to this issue and perform some improvement programs.
PMID- 26430683
TI - Mustard gas exposure in Iran-Iraq war - A scientometric study.
AB - BACKGROUND: The Iranian victims of sulfur mustard attack are now more than 20
years post-exposure and form a valuable cohort for studying the chronic effects
of an exposure to sulfur mustard. Articles on sulfur mustard exposure in Iran
Iraq war were reviewed using three known international databases such as Scopus,
Medline, and ISI. The objectives of the study were measurement of the author-wise
distribution, year-wise distribution, subject area wise, and assessment of highly
cited articles. MATERIALS AND METHODS: We searched three known international
databases, Scopus, Medline, and the international statistical institute (ISI),
for articles related to mustard gas exposure in Iran-Iraq war, published between
1988 and 2012. The results were analyzed using scientometric methods. RESULTS:
During the 24 years under examination, about 90 papers were published in the
field of mustard gas in Iran-Iraq war. Original article was the most used
document type forming 51.4% of all the publications. The number of articles
devoted to mustard gas and Iran-Iraq war research increased more than 10-fold,
from 1 in 1988 to 11 in 2011. Most of the published articles (45.7%) included
clinical and paraclinical investigations of sulfur mustard in Iranian victims.
The most highly productive author was Ghanei who occupied the first rank in the
number of publications with 20 papers. The affiliation of most of the researchers
was Baqiyatallah Medical Sciences University (research center of chemical
injuries and dermatology department) in Iran. CONCLUSION: This article has
highlighted the quantitative share of Iran in articles on sulfur mustard and lays
the groundwork for further research on various aspects of related problems.
PMID- 26430682
TI - Positive changes after breast cancer: A qualitative study.
AB - INTRODUCTION: Traumatic events such as breast cancer along with negative effects
on patients also have positive effects. These cases have been studied less in
Iran. Therefore, this study was conducted with the aim of explanation of positive
changes after breast cancer by using a qualitative approach. MATERIALS AND
METHODS: This qualitative study was conducted in 2012 in one of the specialized
centers for cancer affiliated to Isfahan University of Medical Sciences. In this
study, it was interviewed with 19 women with breast cancer about positive changes
after cancer by using individual, open and deep methods. The interviews were
analyzed with conventional content analysis method. RESULTS: The titles of the
three major categories were included as behavioral changes to maintain and
promote health (acquisition of health information and adopting promoting health
behaviors), spiritual development (attention to the God and sense of meaning in
life, revising the values and priorities, strengthening moral and behavioral
traits) and personal growth and flourish (feeling empowerment, confidence and
efforts to achieve the goals and desires). These three categories have led to
emerge themes in this study as the "Awakening after cancer." CONCLUSIONS: The
results of this study indicated positive changes after breast cancer. Considering
such changes while providing care and consulting to patients with breast cancer
in addition to facilitate and accelerate positive changes will be prompted to
provide care and proper and influential consulting to promote patient health.
PMID- 26430684
TI - Resources of learning through hidden curriculum: Iranian nursing students'
perspective.
AB - BACKGROUND: Students tend to internalize and perpetuate the patterns of behavior
and the values surrounding them. Review of literature showed that there are
several student learning sources through the hidden curriculum, but they have not
been identified in nursing yet. Hence, the purpose of this study is explanation
of learning resources in the hidden curriculum in the view of baccalaureate
nursing students. MATERIALS AND METHODS: This qualitative study was carried out
in 2012 with the participation of 32 baccalaureate nursing students in Nursing
and Midwifery College of Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Iran by purposeful sampling strategies. Data were collected by semi-structured
interviews and continued to the level of data saturation and themes' emergence.
Data analysis was performed through inductive content analysis method. RESULT:
"Instructor as the unique learning element," "various learning resources in the
clinical setting," and "instructive nature of the education environment" were
extracted as the main themes, each of which incorporated some categories.
CONCLUSION: Baccalaureate undergraduate nursing students learnt the hidden
curriculum by the resources such as instructors, resources existing in the
clinical setting, and the university campus. Therefore, more research is
recommended for the identification of other resources. In order to promote
positive messages and reduce the negative messages of the hidden curricula
running at academic and clinical settings, nursing educators and nurses need to
learn more about this issue in the nursing profession.
PMID- 26430685
TI - Meta-analysis of the efficacy of psychological and educational interventions to
improve academic performance of students with learning disabilities in Iran.
AB - INTRODUCTION: with due attention to the importance of learning disabilities and
necessity of presenting interventions for improvement of these disorders in order
to prevent future problems, this study used meta-analysis of the research model
on the impact of psychological and educational interventions to improve academic
performance of students with learning disabilities. METHODS: with the use of meta
analysis method by integrating the results of various researches, this study
specifies the effect of psychological and educational interventions. In this
order, 57 studies, which their methodology was accepted, were selected and meta
analysis was performed on them. The research instrument was a meta-analysis
checklist. RESULTS: The effect size for the effectiveness of psychological
educational interventions on improving the academic performance of students with
mathematics disorder (0.57), impaired writing (0.50) and dyslexia (0.55) were
reported. CONCLUSIONS: The result of meta-analysis showed that according to
Cohen's table, the effect size is above average, and it can be said that
educational and psychological interventions improve the academic performance of
students with learning disabilities.
PMID- 26430686
TI - Investigating the mental health and coping strategies of parents with major
thalassemic children in Bandar Abbas.
AB - INTRODUCTION: Major thalassemia is a hereditary, chronic blood disease caused by
the synthesis deficiency of one or more polypeptide chains of globin during
childhood. This leads to the rise of blood pressure and family tensions.
Therefore, the coping strategies of the family could seriously affect and
facilitate the thalassemic child's healthy growth. The present research sought to
investigate the mental health and coping strategies of families with major
thalassemic children in Bandar Abbas in 2013. MATERIALS AND METHODS: This study
is of a descriptive-analytical and cross-sectional type. Research population
consisted of 140 parents of major thalassemic children who visited Shahid
Mohammadi Hospital of Bandar Abbas. The instruments used were the 12-item General
Health Questionnaire of Goldberg and Williams along with the coping strategies
questionnaire. Nonprobabilistic, convenient sampling method was used. To analyze
the data, Spearman's correlation coefficient, Chi-square and descriptive
statistical tests were used. The significance level was set at P < 0.05. RESULTS:
Data analysis showed that parents' mental health (32 +/- 4.25) along with their
coping strategy scores (45 +/- 7.50) was about the average. The most prevalent
coping strategies among the parents were represented as: "I trust in God in order
to get my problems solved" (87%), "to get mentally and spiritually relieved, I
would visit mosques and holy shrines" (53%), and "to overcome problems, I make
harder attempts" (50.7%). A significant correlation was found between the
parents' coping strategies and general health (P < 0.001). A significant
correlation was also observed between mother's educational level (P = 0.044), age
(P = 0.022) and general health. DISCUSSION AND CONCLUSION: According to the
results of this research, it is categorical for the ministry of health and
medical education and those in charge to pay special and adequate attention to
the social, spiritual, and mental health of these children and their families.
PMID- 26430687
TI - Nejat Briefcase: A tool for drug education.
AB - BACKGROUND: On account of the prevalence of psychoactive substances and drug
abuse and its diversity of forms and methods of use, along with the reduction in
the age of drug abuse, a continuing medical educationof physicians with these
issues is necessary. Although it is legally forbidden, most physicians have no
close contact to these drugs, and this is not effective for training, prevention
and treatment of drug addiction. In this regard, offering an educational tool is
needed, if in close contact to these drugs. The 'Nejat Briefcase' is a tool
designed for the purpose of training and familiarization of psychoactive
substances and drugs. The aim of this study is to investigate the points of view
of the participants in the continuing medical education program, 'Introduction to
types of psychoactive substances and drugs' and about the Nejat Briefcase, in the
Isfahan University of Medical Sciences (IUMS). MATERIALS AND METHODS: In this
descriptive, cross-sectional study, all the general physicians (108 people) who
participated in the continuing medical education program, 'Introducing types of
psychoactive substances and drugs,' in the Isfahan University of Medical Sciences
(IUMS), in 2012 - 2013, were considered. In this program, in order to introduce
various types of psychoactive substances and drugs to the physicians, as well as
acquaint them with their forms, methods of use, and prices, the new educational
tool (Nejat Briefcase), containing various types of psychoactive substances and
drugs and the related educational packages, such as, booklets and brochures, was
used. A researcher-made, valid and reliable questionnaire was distributed at the
end of program to gather the participants' points of view about the educational
program. Data was analyzed by the SPSS and t-test and descriptive statistical
tests. RESULTS AND DISCUSSION: The response rate to the questionnaire was 83%.
Forty-four people (41%) were women and 64 (59%) were men. The mean total score of
the participants' points of view was 4/58 +/- 0/45 (out of 5), which indicated
the positive points of view of the participants. Ninety-seven people (90%) were
satisfied with the program. CONCLUSIONS: On account of the participants' positive
points of view on the Nejat Briefcase and their consent to it, using varied and
attractive educational tools for psychoactive substances and drug training and
producing tools similar to the Nejat Briefcase are proposed.
PMID- 26430688
TI - An investigation of the effects of therapeutic touch plan on acute chemotherapy
induced nausea in women with breast cancer in Isfahan, Iran, 2012-2013.
AB - INTRODUCTION: Nausea is the worst and most prevalent chemotherapy-induced
complication experienced by 70-80% of patients despite mediation therapy.
Reduction of nausea is one of the most important roles of oncologist nurses.
Today, complementary therapies in addition to classic medicine, because of their
lower costs, receive much attention. Nonetheless, their safety and effectiveness
are not yet proven. The purpose of this research was to investigate the effect of
therapeutic touch plan as a complementary therapy on acute nausea in women with
breast cancer in 2012-2013 in Isfahan, Iran. MATERIALS AND METHODS: A quasi
experimental, single-blind, randomized control trial with three groups (control,
placebo and intervention) was performed at the Isfahan Seyedolshohada (AS)
Teaching Hospital, Isfahan, in 2012-2013. The intervention was therapeutic touch
plan on women with breast cancer, with the three groups receiving the same
medicine regimen. Information was recorded by a checklist after infusion of
chemotherapy drugs. Data analysis was performed by SPSS, ANOVA and Kruskal-Wallis
tests. RESULTS: The ANOVA test showed that the therapeutic touch plan was
significantly effective in reducing the duration of nausea compared with the
control and placebo groups (P < 0.001). The Kruskal-Wallis test showed that the
frequency of occurrence of nausea was also reduced in the intervention and
placebo groups compared with the control group (P < 0.001). The therapeutic touch
plan was significantly effective in delaying the onset of nausea compared with
the control and placebo groups (P < 0.001). CONCLUSION: This research showed that
the therapeutic touch plan is effective in reducing acute chemotherapy-induced
nausea; thus, education and implementation of the therapeutic touch plan is
proposed for clinical nurses.
PMID- 26430689
TI - One of early maladaptive schemas' causal relationship through metacognitive
beliefs with borderline and antisocial personality patterns.
AB - INTRODUCTION: This study aimed at determining the causal relationship of
metacognitive beliefs as a mediator between one of early maladaptive schemas
including (emotional deprivation, abandonment, mistrust/abuse, social
isolation/alienation and defectiveness/shame) and borderline and antisocial
personality patterns. MATERIALS AND METHODS: The study type has been relational
and seeking causal modeling of path analysis has been used. The population used
in this study included outpatients in counseling, psychological and psychiatric
centers in 2012-2013. We randomly distributed 350 questionnaires in five centers
out of three parts in Isfahan, and finally 230 valid questionnaires were
evaluated and analyzed. Data collection tool has been Millon Clinical Multiaxial
Inventory-III's (MCMI-III's) personality questionnaire, Yang's schema
questionnaire (75 items), Metacognition Questionnaire-30 (30 items). Reliability
of the Yang's Schema Questionnaire in this study was calculated by Cronbach's
alpha (alpha =96%), and that of metacognition was calculated the same way (alpha
=87%). Data analysis has been done using MCMI-III's software for Millon's
personality questionnaire, and SPSS-16 and AMOS-18 software. We used path
analysis method for testing each model in statistical data analysis. RESULT: The
results of this study suggest a possible causal relationship between the number
of one of the early maladaptive schemas and the patterns of anti-social and
borderline personalities through some metacognitive beliefs. CONCLUSION: This
study showed that cognitive beliefs can be activators of the early schema and
continuation's coping behaviors in personality patterns.
PMID- 26430690
TI - The impact of emotional intelligence on managers' performance: Evidence from
hospitals located in Tehran.
AB - CONTEXT: Most of the studies show that emotional intelligence (EI) is an
important factor for effective leadership and team performance in organizations.
AIMS: This research paper aims to provide an exploratory analysis of EI in the
hospitals managers located in Tehran, and examine its relation to their
performance. SETTINGS AND DESIGN: The present research was an analytical and
cross-sectional study. Setting of the study was hospitals located in Tehran,
Iran. SUBJECTS AND METHODS: We conducted a cross-sectional study from a matched
sample of 120 managers and 360 subordinates in hospitals located in Tehran.
Cyberia shrink EI measure was used for assessing the EI of the participants.
Moreover, a management performance Questionnaire is specifically developed for
the present study. The total of 480 questionnaires analyzed throughout Kolmogorov
Smirnov, Mann-Whitney, and Kruskal-Wallis tests in SPSS. RESULTS: The findings
suggested a poor EI among hospital managers. As for EI subscales, social skills
and self-motivation were in the highest and lowest levels respectively. Moreover,
the results indicated that EI increases with experience. The results also showed
there is no significant relationship between the components of EI and the
performance of hospital managers. CONCLUSIONS: Present research indicated that
higher levels of EI did not necessarily lead to better performance in hospital
managers.
PMID- 26430691
TI - The effect of intervention based on Health Action Model to promote workers' safe
behavior in Isfahan Steel Company.
AB - BACKGROUND: The worldwide concern for safety has created the need for new and
effective methods to improve safety in the workplace. This study was designed to
determine the effect of educational intervention based on Health Action Model on
the safe behavior among workers in Isfahan Steel Company. MATERIALS AND METHODS:
This study was designed as a quasi-experimental research with experimental and
control groups with pre- and post- intervention measurements. The experimental
group received intervention based on the Health Action Model. The control group
did not receive any intervention except that they participated in the current
safety courses of the company. The sample size was 270 workers who were randomly
selected and divided into two groups: Experimental (n = 135) and control (n =
135). Data were collected using a questionnaire and a checklist after and before
the intervention and were analyzed. Based on the distribution of variables,
parametric (t-test, paired t-test) or nonparametric (Chi-square, Wilcoxon) tests
were utilized to analyze data. P value less than 0.05 was considered significant.
RESULTS: The results indicated that before intervention, the experimental and
control groups were similar in model structures. After intervention, the mean
scores of knowledge, attitude, and behaviors in relation to safety in the
experimental group increased statistically significantly and the observed
difference in the control group was not significant. The results also indicated
that unsafe behaviors in the experimental group decreased following the
educational intervention. This difference also was not statistically significant
in the control group. CONCLUSION: The results showed that application of Health
Action Model has an acceptable and positive influence on promoting safe
behaviors, knowledge, normative system, and facilitating factors among workers in
Isfahan Steel Company. It is, therefore, recommended that Health Action Model
based intervention be used for other and similar industries.
PMID- 26430692
TI - The effect of three ergonomics interventions on body posture and musculoskeletal
disorders among stuff of Isfahan Province Gas Company.
AB - BACKGROUND: Prevalence of work-related musculoskeletal disorders (WMSDs) is high
among computer users. The study investigates the effect of three ergonomic
interventions on the incidence of musculoskeletal disorders among the staff of
Isfahan Province Gas Company, including training, sport, and installation of
software. MATERIALS AND METHODS: The study was performed in the summer of 2013 on
75 (52 men, 23 women) Isfahan Province Gas Company employees in three phases
(phase 1: Evaluation of present situation, phase 2: Performing interventions, and
phase 3: Re-evaluation). Participants were divided into three groups (training,
exercise, and software). The Nordic Musculoskeletal Questionnaire (NMQ) and rapid
upper limb assessment (RULA) were used. Data collected were analyzed using SPSS
software and McNemar test, t-test, and Chi-square test. RESULTS: Based on the
evaluations, there was a decrease in musculoskeletal symptoms among the trained
group participants after they received the training. McNemar test showed that the
lower rate of pain in low back, neck, knee, and wrist was significant (P < 0.05).
The results obtained from the RULA method for evaluation of posture showed an
average 25 points decrease in the right side of the body and 20 points decrease
in the left side of the body in the group subjected to training. Based on t-test,
the decrease was significant. CONCLUSION: The study demonstrated that majority of
the participants accepted interventions, which indicates that most of the people
were unsatisfied with the work settings and seeking improvement at the workplace.
Overall, the findings show that training, chair adjustment, and arrangement in
workplace could decrease musculoskeletal disorders.
PMID- 26430693
TI - A study of the academic performance of medical students in the comprehensive
examination of the basic sciences according to the indices of emotional
intelligence and educational status.
AB - BACKGROUND: Considering the increasing importance of emotional intelligence (EI)
in different aspects of life, such as academic achievement, the present survey is
aimed to predict academic performance of medical students in the comprehensive
examination of the basic sciences, according to the indices of emotional
intelligence and educational status. MATERIALS AND METHODS: The present survey is
a descriptive, analytical, and cross-sectional study performed on the medical
students of Isfahan, Tehran, and Mashhad Universities of Medical Sciences.
Sampling the universities was performed randomly after which selecting the
students was done, taking into consideration the limitation in their numbers.
Based on the inclusion criteria, all the medical students, entrance of 2005, who
had attended the comprehensive basic sciences examination in 2008, entered the
study. The data collection tools included an Emotional Intelligence Questionnaire
(standardized in Isfahan), the average score of the first to fifth semesters,
total average of each of the five semesters, and the grade of the comprehensive
basic sciences examination. The data were analyzed through stepwise regression
coefficient by SPSS software version 15. RESULTS: The results indicated that the
indicators of independence from an emotional intelligence test and average scores
of the first and third academic semesters were significant in predicting the
students' academic performance in the comprehensive basic sciences examination.
CONCLUSION: According to the obtained results, the average scores of students,
especially in the earlier semesters, as well as the indicators of independence
and the self-esteem rate of students can influence their success in the
comprehensive basic sciences examination.
PMID- 26430694
TI - The effect of supplementary calcium on blood pressure in healthy adult women aged
18-30 years in Tehran, Iran.
AB - INTRODUCTION: Cardiovascular disease is the major cause of mortality in developed
countries and has an increasing trend in developing countries. There are some
evidences that calcium supplementation may decrease blood pressure and
consequently cardiovascular disease, but they are not conclusive and there is no
agreement in this respect. The aim of the present study was to assess the effect
of supplementary calcium on systolic and diastolic blood pressure in healthy
adult women aged 18-30 years. MATERIALS AND METHODS: Seventy-five normotensive
volunteers were randomly divided into two groups, the treatment group received
1000 mg/day calcium (four doses of 625 mg calcium carbonate) for 1 month and the
control group received placebo (dextrose). Systolic and diastolic blood pressure
was determined before and after intervention in supine position after 10 min of
rest. RESULTS: The mean daily calcium intake from food was 773.9 mg in treatment
and 721 mg in control group (no significant difference) but in both the groups
dietary calcium intake was less than the recommended dietary allowance: After
calcium supplementation, the mean change of systolic blood pressure was not
significant in the two groups, but diastolic blood pressure reduced in treatment
group and increased in control group (-4.9 vs 2.6 mmHg) (P < 0.05). CONCLUSIONS:
These results suggest that, calcium supplementation does not have any effect on
systolic blood pressure of our volunteers but can decrease diastolic blood
pressure significantly and therefore it seems that calcium supplementation may be
useful for people with increased diastolic blood pressure, especially for those
who receive less calcium than recommended dietary allowance.
PMID- 26430696
TI - Anatomical sketching and education: The next steps.
PMID- 26430695
TI - Prevalence of high normal FBS and prediabetes among adolescents in Birjand, East
of Iran, 2012.
AB - BACKGROUND AND OBJECTIVES: To determine the prevalence of impaired fasting
glucose in adolescents in Birjand city in eastern Iran. MATERIALS AND METHODS:
This cross-sectional study was done on 2653 students aged 11-18 years selected
through multi-stage stratified and random sampling. Fasting blood glucose (FBS)
of these students was measured applying the enzymatic process. The obtained data
were analyzed by means of SPSS software (V: 15) and statistical tests T and X2.
RESULTS: The mean age of individual was 14.5 +/- 2 years. Mean FBS of the whole
population was 89.8 +/- 9.8 mg/dl, but it was significantly higher among boys
than girls (P < 0.001). Out of the whole subjects (92.4%), 1,328 (95.1%) of the
girls and 1,122 (89.3%) of the boys, FBS was less than 100 mg/dl among whom 64.4%
had FBS above 86 mg/dl. In 200 subjects (7.5%) of whole population, FBS was 100
125 mg/dl; with that of the boys was 2.3 times than the girls revealing a
prediabetes condition: OR = 2.3(CI: 1.7-3.2). Among the students, 3 (0.1%) had an
FBS > 126 mg/dl. Mean blood glucose was significant regarding age and sex.
CONCLUSIONS: High prevalence of high FBS (within normal range) among adolescents
is warning and requires special attention of health officials. Screening of
children and adolescents in order to identify those at risk and plan for
intervening is urgent to prevent type-2 diabetes epidemic and following
cardiovascular complications in the Society.
PMID- 26430697
TI - Improving Influenza and Pneumococcal Vaccination Rates in Ambulatory Specialty
Practices.
AB - Background. Influenza and pneumococcal vaccinations are recommended for elderly
and high-risk patients; however, rates of adherence are low. We sought to
implement influenza and pneumococcal vaccine initiatives in 4 different
ambulatory specialty practices, using 3 unique approaches. Methods. Four
specialties with high-risk patient populations were selected for intervention:
allergy (asthma), infectious disease (ID) (human immunodeficiency virus),
pulmonary (chronic lung disease), and rheumatology (immunocompromised). Allergy
and ID focused on influenza vaccination, and pulmonary and rheumatology focused
on pneumococcal vaccination. We used 3 strategies for quality improvement:
physician reminders, patient letters, and a nurse-driven model. Physicians were
provided their performance data on a monthly basis and presented trended data on
a quarterly basis at staff meetings. Results. All 4 specialties developed
processes for improving vaccination rates with all showing some increase. Higher
rates were achieved with pneumococcal vaccine than influenza. Pneumococcal
vaccine rates showed steady improvement from year to year while influenza vaccine
rates remained relatively constant. Allergy's influenza rate was 59% in 2011 and
64% in the 2014 flu season. Infectious disease influenza rates moved from 74% in
the 2011 flu season to 86% for the 2014 season. Pneumococcal vaccine in pulmonary
patients' rate was 52% at the start of intervention in February 2009 and 79% as
of January 2015. Rheumatology rates rose from 50% in February 2009 to 87% in
January 2015. Conclusions. Integrated routine workflow and performance data
sharing can effectively engage specialists and staff in vaccine adherence
improvement. Influenza vaccination may require other approaches to achieve the
rates seen with pneumococcal vaccine.
PMID- 26430698
TI - A Prospective Controlled Trial of an Electronic Hand Hygiene Reminder System.
AB - Background. The use of electronic hand hygiene reminder systems has been
proposed as an approach to improve hand hygiene compliance among healthcare
workers, although information on efficacy is limited. We prospectively assessed
whether hand hygiene activities among healthcare workers could be increased using
an electronic hand hygiene monitoring and reminder system. Methods. A
prospective controlled clinical trial was conducted in 2 medical intensive care
units (ICUs) at an academic medical center with comparable patient populations,
healthcare staff, and physical layout. Hand hygiene activity was monitored
concurrently in both ICUs, and the reminder system was installed in the test ICU.
The reminder system was tested during 3 administered phases including: room
entry/exit chimes, display of real-time hand hygiene activity, and a combination
of the 2. Results. In the test ICU, the mean number of hand hygiene events
increased from 1538 per day at baseline to 1911 per day (24% increase) with the
use of a combination of room entry/exit chimes, real-time displays of hand
hygiene activity, and manager reports (P < .001); in addition, the ratio of hand
hygiene to room entry/exit events also increased from 26.1% to 36.6% (40%
increase, P < .001). The performance returned to baseline (1473 hand hygiene
events per day) during the follow-up phase. There was no significant change in
hand hygiene activity in the control ICU during the course of the trial.
Conclusions. In an ICU setting, an electronic hand hygiene reminder system that
provided real-time feedback on overall unit-wide hand hygiene performance
significantly increased hand hygiene activity.
PMID- 26430699
TI - Coxiella burnetii Infection With Severe Hyperferritinemia in an Asplenic Patient.
AB - Q fever is an uncommon but likely underreported zoonotic infection. Severe
hyperferritinemia has been associated with hemophagocytic lymphohistiocytosis and
other infectious diseases. In this study, we report a case of Coxiella burnetii
infection in an asplenic patient complicated by severe hyperferritinemia and bone
marrow infiltration. In this case, the marked ferritin elevation may have been an
indicator of profound systemic macrophage activation due to preferential
intracellular infection of this cell type by C burnetii, perhaps exacerbated by
altered mononuclear phagocyte system function in the setting of asplenia.
PMID- 26430700
TI - Multiple Pathways Control the Reactivation of Telomerase in HTLV-I-Associated
Leukemia.
AB - While telomerase (hTERT) activity is absent from normal somatic cells,
reactivation of hTERT expression is a hallmark of cancer cells. Telomerase
activity is required for avoiding replicative senescence and supports
immortalization of cellular proliferation. Only a minority of cancer cells rely
on a telomerase-independent process known as alternative lengthening of
telomeres, ALT, to sustain cancer cell proliferation. Multiple genetic,
epigenetic, and viral mechanisms have been found to de-regulate telomerase gene
expression, thereby increasing the risk of cellular transformation. Here, we
review the different strategies used by the Human T-cell leukemia virus type 1,
HTLV-I, to activate hTERT expression and stimulate its enzymatic activity in
virally infected CD4 T cells. The implications of hTERT reactivation in HTLV-I
pathogenesis and disease treatment are discussed.
PMID- 26430701
TI - Titanates and Titanate-Metal Compounds in Biological Contexts.
AB - Metal ions are notorious environmental contaminants, some causing toxicity at
exquisitely low (ppm-level) concentrations. Yet, the redox properties of metal
ions make them attractive candidates for bio-therapeutics. Titanates are
insoluble particulate compounds of titanium and oxygen with crystalline surfaces
that bind metal ions; these compounds offer a means to scavenge metal ions in
environmental contexts or deliver them in therapeutic contexts while limiting
systemic exposure and toxicity. In either application, the toxicological
properties of titanates are crucial. To date, the accurate measurement of the in
vitro toxicity of titanates has been complicated by their particulate nature,
which interferes with many assays that are optical density (OD)-dependent, and at
present, little to no in vivo titanate toxicity data exist. Compatibility data
garnered thus far for native titanates in vitro are inconsistent and lacking in
mechanistic understanding. These data suggest that native titanates have little
toxicity toward several oral and skin bacteria species, but do suppress mammalian
cell metabolism in a cells-pecific manner. Titanate compounds bind several types
of metal ions, including some common environmental toxins, and enhance delivery
to bacteria or cells. Substantial work remains to address the practical
applicability of titanates. Nevertheless, titanates have promise to serve as
novel vehicles for metal-based therapeutics or as a new class of metal scavengers
for environmental applications.
PMID- 26430702
TI - Transcription Factor Activity Mapping of a Tissue-Specific in vivo Gene
Regulatory Network.
AB - A wealth of physical interaction data between transcription factors (TFs) and DNA
has been generated, but these interactions often do not have apparent regulatory
consequences. Thus, equating physical interaction data with gene regulatory
networks (GRNs) is problematic. Here, we comprehensively assay TF activity,
rather than binding, to construct a network of gene regulatory interactions in
the C. elegans intestine. By manually observing the in vivo tissue-specific
knockdown of 921 TFs on a panel of 19 fluorescent transcriptional reporters, we
identified a GRN of 411 interactions between 19 promoters and 177 TFs. This GRN
shows only modest overlap with physical interactions, indicating that many
regulatory interactions are indirect. We applied nested effects modeling to
uncover information flow between TFs in the intestine that converges on a small
set of physical TF-promoter interactions. We found numerous cell nonautonomous
regulatory interactions, illustrating tissue-to-tissue communication. Altogether,
our study illuminates the complexity of gene regulation in the context of a
living animal.
PMID- 26430703
TI - CNS reservoirs for HIV: implications for eradication.
AB - Controversy exists as to whether the central nervous system (CNS) serves as a
reservoir site for HIV, in part reflecting the varying perspectives on what
constitutes a 'reservoir' versus a mere site of latent viral integration.
However, if the CNS proves to be a site of HIV persistence capable of replicating
and reseeding the periphery, leading to failure of virological control, this
privileged anatomical site would need dedicated consideration during the
development of HIV cure strategies. In this review we discuss the current
literature focused on the question of the CNS as a reservoir for HIV, covering
the clinical evidence for continued CNS involvement despite suppressive therapy,
the theorised dynamics of HIV integration into the CNS, as well as studies
indicating that HIV can replicate independently and compartmentalise in the CNS.
The unique cellular and anatomical sites of HIV integration in the CNS are also
reviewed, as are the potential implications for HIV cure strategies.
PMID- 26430704
TI - Elaine R. Monsen, PhD, RD--A Remembrance.
PMID- 26430705
TI - Retraction. Position of the Academy of Nutrition and Dietetics: Vegetarian Diets.
PMID- 26430706
TI - Robert Spiro Obituary.
PMID- 26430707
TI - ClinGen and Genetic Testing.
PMID- 26430708
TI - Nurses' voices in the forefront.
PMID- 26430709
TI - Awakening the 'sleeping giant'.
PMID- 26430710
TI - How Places Shape Identity: The Origins of Distinctive LBQ Identities in Four
Small U.S. Cities.
AB - Tools from the study of neighborhood effects, place distinction, and regional
identity are employed in an ethnography of four small cities with growing
populations of lesbian, bisexual, and queer-identified (LBQ) women to explain why
orientations to sexual identity are relatively constant within each site, despite
informants' within-city demographic heterogeneity, but vary substantially across
the sites, despite common place-based attributes. The author introduces the
concept of "sexual identity cultures"--and reveals the defining role of cities in
shaping their contours. She finds that LBQ numbers and acceptance, place
narratives, and newcomers' encounters with local social attributes serve as
touchstones. The article looks beyond major categorical differences (e.g.,
urban/rural) to understand how and why identities evolve and vary and to reveal
the fundamental interplay of demographic, cultural, and other city features
previously thought isolatable. The findings challenge notions of identity as
fixed and emphasize the degree to which self-understanding and group
understanding remain collective accomplishments.
PMID- 26430711
TI - The Sound of Stigmatization: Sonic Habitus, Sonic Styles, and Boundary Work in an
Urban Slum.
AB - Based on focus groups and interviews with student renters in an Israeli slum, the
article explores the contributions of differences in sonic styles and
sensibilities to boundary work, social categorization, and evaluation. Alongside
visual cues such as broken windows, bad neighborhoods are characterized by sonic
cues, such as shouts from windows. Students understand "being ghetto" as being
loud in a particular way and use loudness as a central resource in their boundary
work. Loudness is read as a performative index of class and ethnicity, and the
performance of middle-class studentship entails being appalled by stigmatized
sonic practices and participating in their exoticization. However, the sonic is
not merely yet another resource of boundary work. Paying sociological attention
to senses other than vision reveals complex interactions between structures
anchored in the body, structures anchored in language, and actors' identification
strategies, which may refine theorizations of the body and the senses in social
theory.
PMID- 26430712
TI - Caste and Choice: The Influence of Developmental Idealism on Marriage Behavior.
AB - Is the marriage behavior of young people determined by their socioeconomic
characteristics or their endorsement of developmental idealism? This article
addresses this question using a unique longitudinal data set from Nepal and
provides the first individual-level test of developmental idealism theory. The
authors find that unmarried individuals with greater endorsement of developmental
idealism in 2008 were more likely by 2012 to choose their own spouse, including a
spouse of a different caste, rather than have an arranged marriage. Those with
salaried work experience were also less likely to have arranged marriages, but
urban proximity and education were not significant. The authors conclude that
both developmental idealism and socioeconomic characteristics influence marriage
and that their influences are largely independent.
PMID- 26430714
TI - Human induced pluripotent stem cell-derived beating cardiac tissues on paper.
AB - There is a growing interest in using paper as a biomaterial scaffold for cell
based applications. In this study, we made the first attempt to fabricate a paper
based array for the culture, proliferation, and direct differentiation of human
induced pluripotent stem cells (hiPSCs) into functional beating cardiac tissues
and create "a beating heart on paper." This array was simply constructed by
binding a cured multi-well polydimethylsiloxane (PDMS) mold with common,
commercially available paper substrates. Three types of paper material (print
paper, chromatography paper and nitrocellulose membrane) were tested for
adhesion, proliferation and differentiation of human-derived iPSCs. We found that
hiPSCs grew well on these paper substrates, presenting a three-dimensional (3D)
like morphology with a pluripotent property. The direct differentiation of human
iPSCs into functional cardiac tissues on paper was also achieved using our
modified differentiation approach. The cardiac tissue retained its functional
activities on the coated print paper and chromatography paper with a beating
frequency of 40-70 beats per min for up to three months. Interestingly, human
iPSCs could be differentiated into retinal pigment epithelium on nitrocellulose
membrane under the conditions of cardiac-specific induction, indicating the
potential roles of material properties and mechanical cues that are involved in
regulating stem cell differentiation. Taken together, these results suggest that
different grades of paper could offer great opportunities as bioactive, low-cost,
and 3D in vitro platforms for stem cell-based high-throughput drug testing at the
tissue/organ level and for tissue engineering applications.
PMID- 26430713
TI - Competition and collaboration between different actin assembly pathways allows
for homeostatic control of the actin cytoskeleton.
AB - Tremendous insight into actin-associated proteins has come from careful
biochemical and cell biological characterization of their activities and
regulation. However, many studies of their cellular behavior have only considered
each in isolation. Recent efforts reveal that assembly factors compete for
polymerization-competent actin monomers, suggesting that actin is homeostatically
regulated. It seems that a major regulatory component is competition between
Arp2/3-activating nucleation promoting factors and profilin for actin monomers.
The result is differential delivery of actin to different pathways, allowing for
simultaneous assembly of competing F-actin structures and collaborative building
of higher order cellular structures. Although there are likely to be additional
factors that regulate actin homeostasis, especially in a cell type-dependent
fashion, we advance the notion that competition between actin assembly factors
results in a tunable system that can be adjusted according to extracellular and
intracellular cues.
PMID- 26430715
TI - Increased insulin-like growth factor 1 receptor (IGF1R) expression in small cell
lung cancer and the effect of inhibition of IGF1R expression by RNAi on growth of
human small cell lung cancer NCI-H446 cell.
AB - Insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase receptor
implicated in tumourigenesis that may be an attractive target for anti-cancer
treatment. In this study, the expression and clinical significance of IGF1R were
investigated in serum and lung cancer tissues from small cell lung cancinoma
(SCLC). We also compared the effect of IGF1R up-regulation and IGF1R inhibition
on viability and apoptosis of NCI-H446 cells. We found the concentration of IGF1R
in blood serum was significantly increased and positive IGF1R protein in cancer
tissue was more prevalent in SCLC. A statistically significant correlation among
IGF1R-positve tumors, lymph node metastasis and local invasion was discussed.
Furthermore, IGF1R overexpression lead to an increase of cell survival and
suppressed cell apoptosis, IGF1R silencing mediated by RNAi abrogate this
response of NCI-H446 cells. Our results further demonstrated that the effects of
these treatments may be assigned to the effective inhibition of lung cancer cells
from Akt/P27(Kip1) pathway in IGF-1R signaling. These features may have important
implications for future anti-IGF1R therapeutic approaches.
PMID- 26430716
TI - Cross-border outbreak of Salmonella enterica ssp. enterica serovar
Bovismorbificans: multiple approaches for an outbreak investigation in Germany
and Switzerland.
AB - QUESTION UNDER STUDY: In July 2014, an outbreak of Salmonella enterica ssp.
enterica serovar Bovismorbificans was detected in Switzerland. The goal of the
outbreak investigation was to rapidly identify and eliminate the contamination
source in order to prevent new cases. METHODS: A case-case study design was
applied comprising reported cases of S. Bovismorbificans and cases of other
serovars. A trawling questionnaire was administered by telephone interview. Data
were collected for 34 cases (20 S. Bovismorbificans and 14 Salmonella spp.)
pertaining to food consumption during the 72 hours prior to symptom onset.
RESULTS: A statistically significant association between an S. Bovismorbificans
infection and the consumption of 'salads' (odds ratio [OR] 14.3, 95% confidence
interval [CI] 1.47-138.27) as well as the consumption of 'sprouts' (OR 10.6, 95%
CI 1.16-97.59) was found. Principal places of consumption of 'salads' and
'sprouts' in outbreak cases were restaurants in southern Germany (80.0%, 95% CI
56.3%-94.3%). Microbiological analysis in Germany identified S. Bovismorbificans
on sprouts, and genotype analysis confirmed that Swiss and German cases shared
the same outbreak strain. The contaminated products were removed from the market
in Germany, preventing an on-going outbreak. CONCLUSION: The combination of the
applied methods and the collaboration between the two countries proved to be
crucial elements of this investigation. A series of sprouts-associated
salmonellosis outbreaks underpin the importance of this vegetable as a potential
food-borne pathogen carrier.
PMID- 26430717
TI - One-Pot Synthesis of Pyrrolo[3,2,1-kl]phenothiazines through Copper-Catalyzed
Tandem Coupling/Double Cyclization Reaction.
AB - A novel and efficient synthesis of pyrrolo[3,2,1-kl]phenothiazines has been
developed through a Cu(I)-catalyzed tandem C-S coupling/double cyclization
process. Using 2-alkynyl-6-iodoanilines and o-bromobenzenethiols as the starting
materials, a wide range of pyrrolo[3,2,1-kl]phenothiazine derivatives were
facilely and efficiently generated in one pot under Cu(I) catalysis.
PMID- 26430718
TI - Iron Catalyzed Dual-Oxidative Dehydrogenative (DOD) Tandem Annulation of Glycine
Derivatives with Tetrahydrofurans.
AB - A novel iron-catalyzed dual-oxidative dehydrogenative (DOD) tandem annulation of
glycine derivatives with tetrahydrofurans (THFs) for the synthesis of high value
quinoline fused lactones has been developed. The reactions were performed under
mild reaction conditions. And the use of cheap substrates (glycine derivatives
and THF) and an even cheaper simple inorganic iron salt as the catalyst makes
this protocol very attractive for potential synthetic applications.
PMID- 26430719
TI - Cervical spinal cord compression from delayed epidural scar tissue formation
around plate lead for SCS. Case report and literature review.
AB - : Cervical spinal compression is a serious and rare complication of spinal cord
stimulation (SCS) that can occur using leads placed via open surgical approach.
The present report describe a case of cervical plate lead implant that developed
spinal and radicular compression symptoms after seven years due to the growth of
fibrotic epidural mass at the level of lead. A review of literature is provided.
CASE PRESENTATION: A 59-year-old woman with 3-year history of left arm post
traumatic complex regional pain syndrome (CRPS) was treated with SCS performed
with the implant of paddle lead in the epidural space from C3-C5. Seven years
later she reported progressive paresthesia along the spine and the limbs, gait
ataxia with sensation of weakness in the legs, increased muscle tone and tendon
reflexes in the lower extremities and decrease in effectiveness of stimulation.
Cervical CT showed a tissue mass into the cervical canal posteriorly to the lead.
This finding was confirmed by MR performed after lead removal that also allowed
to document the amount of spinal cord compression. The patient underwent C4-C5-C6
laminectomy and a thick scar was removed from the dura. After surgery there was
progressive and incomplete improvement of neurological signs but symptoms related
to algodystrophy recurred partly. CONCLUSION: The formation of hypertrophic
epidural scar tissue at the level of lead implant must be taken into
consideration in presence of the onset of progressive cervical myelopathy in
patient treated with SCS using laminectomy lead.
PMID- 26430720
TI - Long-Term Follow-Up of HIV-Infected Women with Cervical Dysplasia.
PMID- 26430721
TI - Depression and HIV Serostatus Disclosure to Sexual Partners Among Newly HIV
Diagnosed Men Who Have Sex with Men.
AB - HIV disclosure to sexual partners facilitates joint decision-making and risk
reduction strategies for safer sex behaviors, but disclosure may be impacted by
depression symptoms. Disclosure is also associated with disclosure self-efficacy,
which in turn may also be influenced by depressive symptoms. This study examined
the relationship between depression and HIV disclosure to partners following
diagnosis among men who have sex with men (MSM), mediated by disclosure self
efficacy. Newly HIV-diagnosed MSM (n=92) who reported sexual activity after
diagnosis completed an assessment soon after diagnosis which measured depressive
symptoms, and another assessment within 3 months of diagnosis that measured
disclosure self-efficacy and disclosure. Over one-third of the sample reported
elevated depressive symptoms soon after diagnosis and equal proportions (one
third each) disclosed to none, some, or all partners in the 3 months after
diagnosis. Depressive symptoms were negatively associated with disclosure self
efficacy and disclosure to partners, while disclosure self-efficacy was
positively associated with disclosure. Disclosure self-efficacy partially
mediated the relationship between depression and disclosure, accounting for 33%
of the total effect. These findings highlight the importance of addressing
depression that follows diagnosis to enhance subsequent disclosure to sexual
partners.
PMID- 26430722
TI - Concomitant JAK2 V617F-positive polycythemia vera and BCR-ABL-positive chronic
myelogenous leukemia treated with ruxolitinib and dasatinib.
PMID- 26430723
TI - The expression level of BAALC-associated microRNA miR-3151 is an independent
prognostic factor in younger patients with cytogenetic intermediate-risk acute
myeloid leukemia.
AB - Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly
related to the biological risk conferred by cytogenetics and molecular profiling.
In elderly patients (?60 years) with normal karyotype AML miR-3151 have been
identified as a prognostic factor. However, miR-3151 prognostic value has not
been examined in younger AML patients. In the present work, we have studied miR
3151 alone and in combination with BAALC, its host gene, in a cohort of 181
younger intermediate-risk AML (IR-AML) patients. Patients with higher expression
of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free
survival (P=0.026) and higher cumulative incidence of relapse (P=0.082).
Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic
marker in both the overall series and within the unfavorable molecular prognostic
category. Interestingly, the combined determination of both miR-3151 and BAALC
improved this prognostic stratification, with patients with low levels of both
parameters showing a better outcome compared with those patients harboring
increased levels of one or both markers (P=0.003). In addition, we studied the
microRNA expression profile associated with miR-3151 identifying a six-microRNA
signature. In conclusion, the analysis of miR-3151 and BAALC expression may well
contribute to an improved prognostic stratification of younger patients with IR
AML.
PMID- 26430724
TI - Gene expression of INPP5F as an independent prognostic marker in fludarabine
based therapy of chronic lymphocytic leukemia.
AB - Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Various disease
related and patient-related factors have been shown to influence the course of
the disease. The aim of this study was to identify novel biomarkers of
significant clinical relevance. Pretreatment CD19-separated lymphocytes (n=237;
discovery set) and peripheral blood mononuclear cells (n=92; validation set) from
the REACH trial, a randomized phase III trial in relapsed CLL comparing rituximab
plus fludarabine plus cyclophosphamide with fludarabine plus cyclophosphamide
alone, underwent gene expression profiling. By using Cox regression survival
analysis on the discovery set, we identified inositol polyphosphate-5-phosphatase
F (INPP5F) as a prognostic factor for progression-free survival (P<0.001; hazard
ratio (HR), 1.63; 95% confidence interval (CI), 1.35-1.98) and overall survival
(P<0.001; HR, 1.47; 95% CI, 1.18-1.84), regardless of adjusting for known
prognostic factors. These findings were confirmed on the validation set,
suggesting that INPP5F may serve as a novel, easy-to-assess future prognostic
biomarker for fludarabine-based therapy in CLL.
PMID- 26430725
TI - Rate of CRL4(CRBN) substrate Ikaros and Aiolos degradation underlies differential
activity of lenalidomide and pomalidomide in multiple myeloma cells by regulation
of c-Myc and IRF4.
AB - Recent discoveries suggest that the critical events leading to the anti
proliferative activity of the IMiD immunomodulatory agents lenalidomide and
pomalidomide in multiple myeloma (MM) cells are initiated by Cereblon-dependent
ubiquitination and proteasomal degradation of substrate proteins Ikaros (IKZF1)
and Aiolos (IKZF3). By performing kinetic analyses, we found that the
downregulation or proteasomal degradation of Ikaros and Aiolos led to specific
and sequential downregulation of c-Myc followed by IRF4 and subsequent growth
inhibition and apoptosis. Notably, to ensure growth inhibition and cell death,
sustained downregulation of Ikaros and Aiolos, c-Myc or IRF4 expression was
required. In addition, we found that the half-maximal rate, rather than the final
extent of Ikaros and Aiolos degradation, correlated to the relative efficacy of
growth inhibition by lenalidomide or pomalidomide. Finally, we observed that all
four transcription factors were elevated in primary MM samples compared with
normal plasma cells. Taken together, our results suggest a functional link
between Ikaros and Aiolos, and the pathological dysregulation of c-Myc and IRF4,
and provide a new mechanistic understanding of the relative efficacy of
lenalidomide and pomalidomide based on the kinetics of substrate degradation and
downregulation of their downstream targets.
PMID- 26430726
TI - Nurse-like cells mediate ibrutinib resistance in chronic lymphocytic leukemia
patients.
PMID- 26430727
TI - Patients with relapsed/refractory chronic lymphocytic leukaemia may benefit from
inclusion in clinical trials irrespective of the therapy received: a case-control
retrospective analsysis.
PMID- 26430728
TI - A case of pre-eclampsia and foetal growth restriction after embolisation for a
postmolar uterine arteriovenous malformation.
PMID- 26430729
TI - Tdap vaccine attitudes and utilization among pregnant women from a high-risk
population.
AB - Infants infected with Bordatella pertussis experience high morbidity and
significant mortality. Vaccinating pregnant mothers with the tetanus-diphtheria
acellular pertussis (Tdap) vaccine is a recommended strategy for preventing
infant pertussis. This is especially important for mothers living in poverty and
from racial and ethnic minority populations as these groups are at increased risk
of having a pertussis-affected infant. Using the Health Belief Model as a
framework, we surveyed a convenience sample of pregnant mothers representing
these high-risk populations to understand factors associated with Tdap vaccine
uptake during their pregnancy. Among the 316 mothers surveyed, 82% had gotten or
planned to get Tdap that same day even though 63% of the sample had concerns
about the safety of the vaccine during pregnancy. Perceived benefits and norms
were the Health Belief Model constructs most consistently associated with Tdap
vaccination. Although 32% of women reported prior Tdap vaccine receipt, this
factor was not associated with Tdap vaccination during the current pregnancy,
contrasting studies of vaccination done in non-pregnant populations. Important
variations in attitudes were apparent, with Spanish-speaking women significantly
more likely to have concerns about the vaccine's safety and efficacy than English
speaking women. This study indicates that among this high-risk population
acceptance of Tdap vaccine during pregnancy is high. However, our results suggest
that it may be important to modify information conveyed about the safety and
importance of Tdap during pregnancy based on individual level factors such as
language or acculturation.
PMID- 26430730
TI - Tobacco outlet density, retailer cigarette sales without ID checks and
enforcement of underage tobacco laws: associations with youths' cigarette smoking
and beliefs.
AB - AIMS: To estimate the relationships of tobacco outlet density, cigarette sales
without ID checks and local enforcement of underage tobacco laws with youth's
life-time cigarette smoking, perceived availability of tobacco and perceived
enforcement of underage tobacco laws and changes over time. DESIGN: The study
involved: (a) three annual telephone surveys, (b) two annual purchase surveys in
2000 tobacco outlets and (c) interviews with key informants from local law
enforcement agencies. Analyses were multi-level models (city, individual, time).
SETTING: A sample of 50 mid-sized non-contiguous cities in California, USA.
PARTICIPANTS: A total of 1478 youths (aged 13-16 at wave 1, 52.2% male); 1061
participated in all waves. MEASUREMENTS: Measures at the individual level
included life-time cigarette smoking, perceived availability and perceived
enforcement. City-level measures included tobacco outlet density, cigarette sales
without ID checks and compliance checks. FINDINGS: Outlet density was associated
positively with life-time smoking [OR = 1.12, P < 0.01]. An interaction between
outlet density and wave (OR = 0.96, P < 0.05) suggested that higher density was
associated more closely with life-time smoking at the earlier waves when
respondents were younger. Greater density was associated positively with
perceived availability (beta = 0.02, P < 0.05) and negatively with perceived
enforcement (beta = -0.02, P < 0.01). Sales rate without checking IDs was related
to greater perceived availability (beta = 0.01, P < 0.01) and less perceived
enforcement (beta = -0.01, P < 0.01). Enforcement of underage tobacco laws was
related positively to perceived enforcement (beta = 0.06, P < 0.05). CONCLUSIONS:
Higher tobacco outlet density may contribute to life-time smoking among youths.
Density, sales without ID checks and enforcement levels may influence beliefs
about access to cigarettes and enforcement of underage tobacco sales laws.
PMID- 26430731
TI - Compromised Prefrontal Cognitive Control Over Emotional Interference in
Adolescents with Internet Gaming Disorder.
AB - Increased reports of impulsivity and aggression in male adolescents with Internet
gaming might reflect their dysfunction in emotion regulation, particularly in
suppression of negative emotions, which should affect the various stages of
Internet gaming disorder. This study tested the hypothesis that adolescents with
Internet gaming disorder would be more disturbed by the emotional interference
and demonstrate compromised dorsal anterior cingulate cortex (dACC) activation
during a Stroop Match-to-Sample task. In addition, functional connectivity
analysis was conducted to examine the interplays between neural correlates
involved in emotional processing and how they were altered in adolescents with
Internet gaming disorder. The Internet gaming disorder group demonstrated weaker
dACC activation and stronger insular activations to interfering angry facial
stimuli compared with the healthy control group. Negative functional connectivity
between stronger insular activation and weaker dorsolateral prefrontal activation
correlated with higher cognitive impulsivity in adolescents with Internet gaming
disorder. These findings provide evidence of the compromised prefrontal cognitive
control over emotional interference in adolescents with Internet gaming disorder.
PMID- 26430732
TI - t-Darpp overexpression in HER2-positive breast cancer confers a survival
advantage in lapatinib.
AB - Drug resistance is a major barrier to successful cancer treatment. For patients
with HER2-positive breast cancer who initially respond to therapy, the majority
develop resistance within one year of treatment. Patient outcomes could improve
significantly if we can find and exploit common mechanisms of acquired resistance
to different targeted therapies. Overexpression of t-Darpp, a truncated form of
the dual kinase/phosphatase inhibitor Darpp-32, has been linked to acquired
resistance to trastuzumab, a front-line therapy for HER2-positive breast cancer.
Darpp-32 reverses t-Darpp's effect on trastuzumab resistance. In this study, we
examined whether t-Darpp could be involved in resistance to lapatinib, another
HER2-targeted therapeutic. Lapatinib-resistant SKBR3 cells (SK/LapR) showed a
marked change in the Darpp-32:t-Darpp ratio toward a predominance of t-Darpp.
Overexpression of t-Darpp alone was not sufficient to confer lapatinib
resistance, but cells that overexpress t-Darpp partially mimicked the molecular
resistance phenotype observed in SK/LapR cells exposed to lapatinib. SK/LapR
cells failed to down-regulate Survivin and failed to induce BIM accumulation in
response to lapatinib; cells overexpressing t-Darpp exhibited only the failed BIM
accumulation. t-Darpp knock-down reversed this phenotype. Using a fluorescence
based co-culture system, we found that cells overexpressing t-Darpp formed
colonies in lapatinib within 3-4 weeks, whereas parental cells in the same co
culture did not. Overall, t-Darpp appears to mediate a survival advantage in
lapatinib, possibly linked to failed lapatinib-induced BIM accumulation. t-Darpp
might also be relevant to acquired resistance to other cancer drugs that rely on
BIM accumulation to induce apoptosis.
PMID- 26430733
TI - Rapid Removal of Tetrabromobisphenol A by Ozonation in Water: Oxidation Products,
Reaction Pathways and Toxicity Assessment.
AB - Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame
retardants and has attracted more and more attention. In this work, the parent
TBBPA with an initial concentration of 100 mg/L was completely removed after 6
min of ozonation at pH 8.0, and alkaline conditions favored a more rapid removal
than acidic and neutral conditions. The presence of typical anions and humic acid
did not significantly affect the degradation of TBBPA. The quenching test using
isopropanol indicated that direct ozone oxidation played a dominant role during
this process. Seventeen reaction intermediates and products were identified using
an electrospray time-of-flight mass spectrometer. Notably, the generation of
2,4,6-tribromophenol was first observed in the degradation process of TBBPA. The
evolution of reaction products showed that ozonation is an efficient treatment
for removal of both TBBPA and intermediates. Sequential transformation of organic
bromine to bromide and bromate was confirmed by ion chromatography analysis. Two
primary reaction pathways that involve cleavage of central carbon atom and
benzene ring cleavage concomitant with debromination were thus proposed and
further justified by calculations of frontier electron densities. Furthermore,
the total organic carbon data suggested a low mineralization rate, even after the
complete removal of TBBPA. Meanwhile, the acute aqueous toxicity of reaction
solutions to Photobacterium Phosphoreum and Daphnia magna was rapidly decreased
during ozonation. In addition, no obvious difference in the attenuation of TBBPA
was found by ozone oxidation using different water matrices, and the
effectiveness in natural waters further demonstrates that ozonation can be
adopted as a promising technique to treat TBBPA-contaminated waters.
PMID- 26430735
TI - Cultural influences on HIV testing among Latino youth.
AB - Young Latinos aged 13-24 years in the USA are disproportionately impacted upon by
HIV. Despite the elevated risk, lower rates of HIV testing have been documented
among Latino youth relative to other racial/ethnic groups. The objective of the
current study was to examine the influence of acculturation and cultural values
on HIV testing among Latino youth. The study consisted of 51 sexually experienced
young Latinos aged 13-16 years from a major city in the Southeastern USA.
Participants completed a survey on HIV testing history, cultural orientation and
Latino cultural values. Results indicate that 21.6% of the young people had been
tested for HIV. The number of times tested ranged from one to four (M = 1.9 +/-
1.0). HIV testing was associated with US American cultural orientation and
familism (and emphasis on strong family commitment, family support and emotional
closeness). Participants with greater orientation to US American culture were
more likely, whereas those who endorsed higher familism value were less likely,
to have had an HIV test. For participants scoring high on familism, the desire to
maintain family honour may serve as a deterrent to testing. Incorporating
culturally relevant strategies, such as promoting sexual communication and
conversations on HIV prevention within the family, may enhance testing and narrow
the gap in HIV infection between Latino youth and other ethnic groups.
PMID- 26430734
TI - No Observed Effect of Landscape Fragmentation on Pathogen Infection Prevalence in
Blacklegged Ticks (Ixodes scapularis) in the Northeastern United States.
AB - Pathogen prevalence within blacklegged ticks (Ixodes scapularis Say, 1821) tends
to vary across sites and geographic regions, but the underlying causes of this
variation are not well understood. Efforts to understand the ecology of Lyme
disease have led to the proposition that sites with higher host diversity will
result in lower disease risk due to an increase in the abundance of inefficient
reservoir species relative to the abundance of species that are highly competent
reservoirs. Although the Lyme disease transmission cycle is often cited as a
model for this "dilution effect hypothesis", little empirical evidence exists to
support that claim. Here we tested the dilution effect hypothesis for two
pathogens transmitted by the blacklegged tick along an urban-to-rural gradient in
the northeastern United States using landscape fragmentation as a proxy for host
biodiversity. Percent impervious surface and habitat fragment size around each
site were determined to assess the effect of landscape fragmentation on nymphal
blacklegged tick infection with Borrelia burgdorferi and Anaplasma
phagocytophilum. Our results do not support the dilution effect hypothesis for
either pathogen and are in agreement with the few studies to date that have
tested this idea using either a landscape proxy or direct measures of host
biodiversity.
PMID- 26430736
TI - Multi-Parametric Evaluation of Chronic Kidney Disease by MRI: A Preliminary Cross
Sectional Study.
AB - BACKGROUND: The current clinical classification of chronic kidney disease (CKD)
is not perfect and may be overestimating both the prevalence and the risk for
progressive disease. Novel markers are being sought to identify those at risk of
progression. This preliminary study evaluates the feasibility of magnetic
resonance imaging based markers to identify early changes in CKD. METHODS: Fifty
nine subjects (22 healthy, 7 anemics with no renal disease, 30 subjects with CKD)
participated. Data using 3D volume imaging, blood oxygenation level dependent
(BOLD) and Diffusion MRI was acquired. BOLD MRI acquisition was repeated after 20
mg of iv furosemide. RESULTS: Compared to healthy subjects, those with CKD have
lower renal parenchymal volumes (329.6+/-66.4 vs. 257.1+/-87.0 ml, p<0.005),
higher cortical R2* values (19.7+/-3.2 vs. 23.2+/-6.3 s(-1), p = 0.013)
(suggesting higher levels of hypoxia) and lower response to furosemide on
medullary R2* (6.9+/-3.3 vs. 3.1+/-7.5 s(-1), p = 0.02). All three parameters
showed significant correlation with estimated glomerular filtration rate (eGFR).
When the groups were matched for age and sex, cortical R2* and kidney volume
still showed significant differences between CKD and healthy controls. The most
interesting observation is that a small number of subjects (8 of 29) contributed
to the increase in mean value observed in CKD. The difference in cortical R2*
between these subjects compared to the rest were highly significant and had a
large effect size (Cohen's d = 3.5). While highly suggestive, future studies may
be necessary to verify if such higher levels of hypoxia are indicative of
progressive disease. Diffusion MRI showed no differences between CKD and healthy
controls. CONCLUSIONS: These data demonstrate that BOLD MRI can be used to
identify enhanced hypoxia associated with CKD and the preliminary observations
are consistent with the chronic hypoxia model for disease progression in CKD.
Longitudinal studies are warranted to further verify these findings and assess
their predictive value.
PMID- 26430737
TI - TLR1, 2, 4, 6 and 9 Variants Associated with Tuberculosis Susceptibility: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Studies investigating the influence of toll-like receptor (TLR)
polymorphisms and tuberculosis susceptibility have yielded varying and often
contradictory results in different ethnic groups. A meta-analysis was conducted
to investigate the relationship between TLR variants and susceptibility to
tuberculosis, both across and within specific ethnic groups. METHODS: An
extensive database search was performed for studies investigating the
relationship between TLR and tuberculosis (TB) susceptibility. Data was
subsequently extracted from included studies and statistically analysed. RESULTS:
32 articles involving 18907 individuals were included in this meta-analysis, and
data was extracted for 14 TLR polymorphisms. Various genetic models were
employed. An increased risk of TB was found for individuals with the TLR2
rs3804100 CC and the TLR9 rs352139 GA and GG genotypes, while decreased risk was
identified for those with the AG genotype of TLR1 rs4833095. The T allele of TLR6
rs5743810 conferred protection across all ethnic groups. TLR2 rs5743708 subgroup
analysis identified the A allele to increase susceptibility to TB in the Asian
ethnic group, while conferring protection in the Hispanic group. The T allele of
TLR4 rs4986791 was also found to increase the risk of TB in the Asian subgroup.
All other TLR gene variants investigated were not found to be associated with TB
in this meta-analysis. DISCUSSION: Although general associations were identified,
most TLR variants showed no significant association with TB, indicating that
additional studies investigating a wider range of pattern recognition receptors
is required to gain a better understanding of this complex disease.
PMID- 26430738
TI - Antibiotic Resistance of Pseudomonas aeruginosa in Pneumonia at a Single
University Hospital Center in Germany over a 10-Year Period.
AB - BACKGROUND: Pseudomonas aeruginosa is a common cause of community-acquired and
nosocomial-acquired pneumonia. The development of resistance of P. aeruginosa to
antibiotics is increasing globally due to the overuse of antibiotics. This
article examines, retrospectively, the antibiotic resistance in patients with
community-acquired versus nosocomial-acquired pneumonia caused by P. aeruginosa
or multidrug-resistant (MDR) P. aeruginosa. METHODS: Data from patients with
community-acquired and nosocomial-acquired pneumonia caused by P. aeruginosa and
MDR P. aeruginosa were collected from the hospital charts at the HELIOS Clinic,
Witten/Herdecke University, Wuppertal, Germany, between January 2004 and August
2014. An antibiogram was created from all study patients with community-acquired
and nosocomial-acquired pneumonia caused by P. aeruginosa or MDR P. aeruginosa.
RESULTS: A total of 168 patients with mean age 68.1 +/- 12.8 (113 [67.3% males
and 55 [32.7%] females) were identified; 91 (54.2%) had community-acquired and 77
(45.8%) had nosocomial-acquired pneumonia caused by P. aeruginosa. Patients with
community-acquired versus nosocomial-acquired pneumonia had a mean age of 66.4 +/
13.8 vs. 70.1 +/- 11.4 years [59 vs. 54 (64.8% vs. 70.1%) males and 32 vs. 23
(35.2% vs. 29.9%) females]. They included 41 (24.4%) patients with pneumonia due
to MDR P. aeruginosa: 27 (65.9%) community-acquired and 14 (34.1%) nosocomial
acquired cases. P. aeruginosa and MDR P. aeruginosa showed a very high resistance
to fosfomycin (community-acquired vs. nosocomial-acquired) (81.0% vs. 84.2%; 0
vs. 85.7%). A similar resistance pattern was seen with ciprofloxacin (35.2% vs.
24.0%; 70.4% vs. 61.5%), levofloxacin (34.6% vs. 24.5%; 66.7% vs. 64.3%),
ceftazidime (15.9% vs. 30.9; 33.3% vs. 61.5%), piperacillin (24.2% vs. 29.9%;
44.4% vs. 57.1%), imipenem (28.6% vs. 27.3%; 55.6% vs. 50.0%), piperacillin and
tazobactam (23.1% vs. 28.6%; 44.4% vs. 50.0%), tobramycin (28.0% vs. 17.2%; 52.0%
vs. 27.3%), gentamicin (26.4% vs. 18.2%; 44.4% vs. 21.4%), and meropenem (20.2%
vs. 20.3%; 42.3% vs. 50.0%). An elevated resistance of P. aeruginosa and MDR P.
aeruginosa was found for cefepime (11.1% vs. 23.3%; 25.9% vs. 50.0%), and
amikacin (10.2% vs. 9.1%; 27.3% vs. 9.1%). Neither pathogen was resistant to
colistin (P = 0.574). CONCLUSION: While P. aeruginosa and MDR P. aeruginosa were
resistant to a variety of commonly used antibiotics, they were not resistant to
colistin in the few isolates recovered from patients with pneumonia.
PMID- 26430739
TI - MicroRNA Expression in Myocardial Tissue and Plasma of Patients with End-Stage
Heart Failure during LVAD Support: Comparison of Continuous and Pulsatile
Devices.
AB - AIM: Pulsatile flow left ventricular assist devices (pf-LVADs) are being replaced
by continuous flow LVADs (cf-LVADs) in patients with end-stage heart failure
(HF). MicroRNAs (miRs) play an important role in the onset and progression of HF.
Our aim was to analyze cardiac miR expression patterns associated with each type
of device, to analyze differences in the regulation of the induced cardiac
changes. METHODS AND RESULTS: Twenty-six miRs were selected (based on micro-array
data and literature studies) and validated in myocardial tissue before and after
pf- (n = 17) and cf-LVAD (n = 17) support. Of these, 5 miRs displayed a similar
expression pattern among the devices (miR-129*, miR-146a, miR-155, miR-221, miR
222), whereas others only changed significantly during pf-LVAD (miR-let-7i, miR
21, miR-378, miR-378*) or cf-LVAD support (miR-137). In addition, 4 miRs were
investigated in plasma of cf-LVAD supported patients (n = 18) and healthy
controls (n = 10). Circulating miR-21 decreased at 1, 3, and 6 months after LVAD
implantation. MiR-146a, miR-221 and miR-222 showed a fluctuating time pattern
post-LVAD. CONCLUSION: Our data show a different miR expression pattern after
LVAD support, suggesting that differentially expressed miRs are partially
responsible for the cardiac morphological and functional changes observed after
support. However, the miR expression patterns do not seem to significantly differ
between pf- and cf-LVAD implying that most cardiac changes or clinical outcomes
specific to each device do not relate to differences in miR expression levels.
PMID- 26430740
TI - Beyond Testis Size: Links between Spermatogenesis and Sperm Traits in a Seasonal
Breeding Mammal.
AB - Spermatogenesis is a costly process that is expected to be under selection to
maximise sperm quantity and quality. Testis size is often regarded as a proxy
measure of sperm investment, implicitly overlooking the quantitative assessment
of spermatogenesis. An enhanced understanding of testicular function, beyond
testis size, may reveal further sexual traits involved in sperm quantity and
quality. Here, we first estimated the inter-male variation in testicular function
and sperm traits in red deer across the breeding and non-breeding seasons. Then,
we analysed the relationships between the testis mass, eight parameters of
spermatogenic function, and seven parameters of sperm quality. Our findings
revealed that the Sertoli cell number and function parameters vary greatly
between red deer males, and that spermatogenic activity co-varies with testis
mass and sperm quality across the breeding and non-breeding seasons. For the
first time in a seasonal breeder, we found that not only is the Sertoli cell
number important in determining testis mass (r = 0.619, p = 0.007 and r = 0.248,
p = 0.047 for the Sertoli cell number assessed by histology and cytology,
respectively), but also sperm function (r = 0.703, p = 0.002 and r = 0.328, p =
0.012 for the Sertoli cell number assessed by histology and cytology,
respectively). Testicular histology also revealed that a high Sertoli cell number
per tubular cross-section is associated with high sperm production (r = 0.600, p
= 0.009). Sperm production and function were also positively correlated (r =
0.384, p = 0.004), suggesting that these traits co-vary to maximise sperm
fertilisation ability in red deer. In conclusion, our findings contribute to the
understanding of the dynamics of spermatogenesis, and reveal new insights into
the role of testicular function and the Sertoli cell number on testis size and
sperm quality in red deer.
PMID- 26430741
TI - MicroRNA-199a-5p Regulates the Proliferation of Pulmonary Microvascular
Endothelial Cells in Hepatopulmonary Syndrome.
AB - BACKGROUND/AIMS: Pulmonary microvascular endothelial cell (PMVEC) proliferation
and angiogenesis contribute to the development of hepatopulmonary syndrome (HPS).
MicroRNA-199a-5p (miR-199a-5p) has emerged as a potent regulator of angiogenesis,
and its expression levels significantly decrease in the serum of patients with
hepatopathy. However, it has not been reported about whether miR-199a-5p might
control PMVEC proliferation. Here, we described the miR-199a-5p governing PMVEC
proliferation in HPS. METHODS: PMVECs were treated with rat serum from common
bile duct ligation (CBDL) or sham. MiR-199a-5p mimic or inhibitor was used to
change the miR-199a-5p expression. Knockdown of caveolin-1 (Cav-1) was performed
using siRNA. NSC-23766 was used to inhibit Rac1 activity. Gene and protein
expressions were quantified by qRT-PCR and western blot. Cell proliferation was
analyzed by 3H-TdR incorporation and CCK-8 assays. Stress fibers were detected by
immunofluorescence. RESULTS: CBDL rat serum induced the down-regulation of miR
199a-5p. Delivery of miR-199a-5p suppressed the CBDL rat serum-induced PMVEC
proliferation whereas knockdown of miR-199a-5p promoted PMVEC proliferation. This
was accompanied by a decrease and an increase in Cav-1 expression, respectively.
Cav-1 siRNA abolished the enhancement of PMVEC proliferation induced by the miR
199a-5p inhibition. Although stress fibers were disrupted in Cav-1 deficient
cells, NSC-23766 increased stress fibers and contributed to cell proliferation.
CONCLUSIONS: CBDL rat serum induced down-regulation of miR-199a-5p in PMVECs,
which led to an increase of Cav-1 gene expression. Increased Cav-1 expression, by
inhibiting Rac1 activity, led to the formation of stress fibers, which contribute
to PMVEC proliferation and thus the pathogenesis of HPS.
PMID- 26430746
TI - Angiotensin II Type 1 Receptor-Mediated Electrical Remodeling in Mouse Cardiac
Myocytes.
AB - We recently characterized an autocrine renin angiotensin system (RAS) in canine
heart. Activation of Angiotensin II Type 1 Receptors (AT1Rs) induced electrical
remodeling, including inhibition of the transient outward potassium current Ito,
prolongation of the action potential (AP), increased calcium entry and increased
contractility. Electrical properties of the mouse heart are very different from
those of dog heart, but if a similar system existed in mouse, it could be
uniquely studied through genetic manipulations. To investigate the presence of a
RAS in mouse, we measured APs and Ito in isolated myocytes. Application of
angiotensin II (A2) for 2 or more hours reduced Ito magnitude, without affecting
voltage dependence, and prolonged APs in a dose-dependent manner. Based on dose
inhibition curves, the fast and slow components of Ito (Ito,fast and IK,slow)
appeared to be coherently regulated by [A2], with 50% inhibition at an A2
concentration of about 400 nM. This very high K0.5 is inconsistent with systemic
A2 effects, but is consistent with an autocrine RAS in mouse heart. Pre
application of the microtubule destabilizing agent colchicine eliminated A2
effects on Ito and AP duration, suggesting these effects depend on intracellular
trafficking. Application of the biased agonist SII ([Sar1-Ile4-Ile8]A2), which
stimulates receptor internalization without G protein activation, caused Ito
reduction and AP prolongation similar to A2-induced changes. These data
demonstrate AT1R mediated regulation of Ito in mouse heart. Moreover, all
measured properties parallel those measured in dog heart, suggesting an autocrine
RAS may be a fundamental feedback system that is present across species.
PMID- 26430747
TI - Determinants of Bed Net Use in Southeast Nigeria following Mass Distribution of
LLINs: Implications for Social Behavior Change Interventions.
AB - Millions of long-lasting insecticide treated nets (LLINs) have been distributed
as part of the global malaria control strategy. LLIN ownership, however, does not
necessarily guarantee use. Thus, even in the ideal setting in which universal
coverage with LLINs has been achieved, maximal malaria protection will only be
achieved if LLINs are used both correctly and consistently. This study
investigated the factors associated with net use, independent of net ownership.
Data were collected during a household survey conducted in Ebonyi State in
southeastern Nigeria in November 2011 following a statewide mass LLIN
distribution campaign and, in select locations, a community-based social behavior
change (SBC) intervention. Logistic regression analyses, controlling for
household bed net ownership, were conducted to examine the association between
individual net use and various demographic, environmental, behavioral and social
factors. The odds of net use increased among individuals who were exposed to
tailored SBC in the context of a home visit (OR = 17.11; 95% CI 4.45-65.79) or
who received greater degrees of social support from friends and family (ptrend <
0.001). Factors associated with decreased odds of net use included: increasing
education level (ptrend = 0.020), increasing malaria knowledge level (ptrend =
0.022), and reporting any disadvantage of bed nets (OR = 0.39; 95% CI 0.23-0.78).
The findings suggest that LLIN use is significantly influenced by social support
and exposure to a malaria-related SBC home visit. The malaria community should
thus further consider the importance of community outreach, interpersonal
communication and social support on adoption of net use behaviors when designing
future research and interventions.
PMID- 26430748
TI - Variations in the Quality of Care at Large Public Hospitals in Beijing, China: A
Condition-Based Outcome Approach.
AB - BACKGROUND: Public hospitals deliver over ninety percent of all outpatient and
inpatient services in China. Their quality is graded into three levels (A, B, and
C) largely based on structural resources, but empirical evidence on the quality
of process and outcome of care is extremely scarce. As expectations for quality
care rise with higher living standards and cost of care, such evidence is
urgently needed and vital to improve care and to inform future health reforms.
METHODS: We compiled and analyzed a multicenter database of over 4 million
inpatient discharge summary records to provide a comprehensive assessment of the
level and variations in clinical outcomes of hospitalization at 39 tertiary
hospitals in Beijing. We assessed six outcome measures of clinical quality: in
hospital mortality rates (RSMR) for AMI, stroke, pneumonia and CABG, post
procedural complication rate (RS-CR), and failure-to-rescue rate (RS-FTR). The
measures were adjusted for pre-admission patient case-mix using indirect
standardization method with hierarchical linear mixed models. RESULTS: We found
good overall quality with large variations by hospital and condition (mean/range,
in %): RSMR-AMI: 6.23 (2.37-14.48), RSMR-stroke: 4.18 (3.58-4.44), RSMR
pneumonia: 7.78 (7.20-8.59), RSMR-CABG: 1.93 (1.55-2.23), RS-CR: 11.38 (9.9
12.88), and RS-FTR: 6.41 (5.17-7.58). Hospital grade was not significantly
associated with any risk-adjusted outcome measures. CONCLUSIONS: Going to a
higher grade public hospital does not always lead to better patient outcome
because hospital grade only contains information about hospital structural
resources. A hospital report card with some outcome measures of quality would
provide valuable information to patients in choosing providers, and for
regulators to identify gaps in health care quality. Reducing the variations in
clinical practice and patient outcome should be a focus for policy makers in the
next round of health sector reforms in China.
PMID- 26430749
TI - A Pilot Study of EEG Source Analysis Based Repetitive Transcranial Magnetic
Stimulation for the Treatment of Tinnitus.
AB - OBJECTIVE: Repetitive Transcranial Magnetic Stimulation (rTMS) is a novel
therapeutic tool to induce a suppression of tinnitus. However, the optimal target
sites are unknown. We aimed to determine whether low-frequency rTMS induced
lasting suppression of tinnitus by decreasing neural activity in the cortex,
navigated by high-density electroencephalogram (EEG) source analysis, and the
utility of EEG for targeting treatment. METHODS: In this controlled three-armed
trial, seven normal hearing patients with tonal tinnitus received a 10-day course
of 1-Hz rTMS to the cortex, navigated by high-density EEG source analysis, to the
left temporoparietal cortex region, and to the left temporoparietal with sham
stimulation. The Tinnitus handicap inventory (THI) and a visual analog scale
(VAS) were used to assess tinnitus severity and loudness. Measurements were taken
before, and immediately, 2 weeks, and 4 weeks after the end of the interventions.
RESULTS: Low-frequency rTMS decreased tinnitus significantly after active, but
not sham, treatment. Responders in the EEG source analysis-based rTMS group,
71.4% (5/7) patients, experienced a significant reduction in tinnitus loudness,
as evidenced by VAS scores. The target site of neuronal generators most
consistently associated with a positive response was the frontal lobe in the
right hemisphere, sourced using high-density EEG equipment, in the tinnitus
patients. After left temporoparietal rTMS stimulation, 42.8% (3/7) patients
experienced a decrease in tinnitus loudness. CONCLUSIONS: Active EEG source
analysis based rTMS resulted in significant suppression in tinnitus loudness,
showing the superiority of neuronavigation-guided coil positioning in dealing
with tinnitus. Non-auditory areas should be considered in the pathophysiology of
tinnitus. This knowledge in turn can contribute to investigate the
pathophysiology of tinnitus.
PMID- 26430754
TI - Integration of photoperiod and cold temperature signals into flowering genetic
pathways in Arabidopsis.
AB - Appropriate timing of flowering is critical for propagation and reproductive
success in plants. Therefore, flowering time is coordinately regulated by
endogenous developmental programs and external signals, such as changes in
photoperiod and temperature. Flowering is delayed by a transient shift to cold
temperatures that frequently occurs during early spring in the temperate zones.
It is known that the delayed flowering by short-term cold stress is mediated
primarily by the floral repressor FLOWERING LOCUS C (FLC). However, how the FLC
mediated cold signals are integrated into flowering genetic pathways is not fully
understood. We have recently reported that the INDUCER OF CBF EXPRESSION 1
(ICE1), which is a master regulator of cold responses, FLC, and the floral
integrator SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) constitute an
elaborated feedforward-feedback loop that integrates photoperiod and cold
temperature signals to regulate seasonal flowering in Arabidopsis. Cold
temperatures promote the binding of ICE1 to FLC promoter to induce its
expression, resulting in delayed flowering. However, under floral inductive
conditions, SOC1 induces flowering by blocking the ICE1 activity. We propose that
the ICE1-FLC-SOC1 signaling network fine-tunes the timing of photoperiodic
flowering during changing seasons.
PMID- 26430755
TI - Correction: Alcohol Advertising in Sport and Non-Sport TV in Australia, during
Children's Viewing Times.
PMID- 26430750
TI - Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced
Protection against Ischemia/Reperfusion Injury in Rat Hearts.
AB - AIMS: Our previous studies demonstrated that remote electro-stimulation (RES)
increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion
(I/R) injury in rat hearts. However, the role of various opioid receptors (OR)
subtypes in preconditioned RES-induced myocardial protection remains unknown. We
investigated the role of OR subtype signaling in RES-induced cardioprotection
against I/R injury of the rat heart. METHODS & RESULTS: Male Spraque-Dawley rats
were used. RES was performed on median nerves area with/without pretreatment with
various receptors antagonists such as opioid receptor (OR) subtype receptors
(KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCepsilon expression were
analyzed by Western blotting. When RES was preconditioned before the I/R model,
the rat's hemodynamic index, infarction size, mortality and serum CK-MB were
evaluated. Our results showed that Akt, GSK3 and PKCepsilon expression levels
were significantly increased in the RES group compared to the sham group, which
were blocked by pretreatment with specific antagonists targeting KOR and DOR, but
not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size
were both significantly attenuated in RES group. The mortality rates of the sham
RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR
antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR
antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.
CONCLUSION: The mechanism of RES-induced myocardial protection against I/R injury
seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.
PMID- 26430760
TI - Correction: Pelvic Belt Effects on Health Outcomes and Functional Parameters of
Patients with Sacroiliac Joint Pain.
PMID- 26430761
TI - Preterm birth and/or low birth weight are associated with periodontal disease and
the increased placental immunohistochemical expression of inflammatory markers.
AB - The objective of this study was to determine whether gynecological and
periodontal clinical parameters and the immunohistochemical expression in
placental chorionic villi of the markers cyclooxygenase-2 (COX-2), interleukin
(IL)-1beta, vascular endothelial growth factor receptor 1 (VEGFR1), podoplanin,
and Heat Shock Protein 70 (HSP70) are associated with preterm birth (PB) and/or
low birth weight (LBW) neonates. MATERIAL AND METHODS: An observational case
control study was performed in 130 puerperal women: mothers of PB/LBW neonates
(cases, n=65) and mothers of full-term normal-weight neonates (controls, n=65).
Data were gathered from all participants on socio-demographic, gynecological, and
periodontal variables and on placental immunohistochemical COX-2, IL-1beta,
VEGFR1, podoplanin, and HSP70 expression. RESULTS: Among the 42 women with
mild/moderate periodontitis or gingivitis, the studied periodontal variables were
significantly worse and the placental COX-2 (p=0.043), HSP70 (p=0.001), IL-1beta
(p=0.001), VEGFR1 (p=0.032), and podoplanin (p=0.058) expressions were
significantly higher in the cases than in the controls. In comparison to the
mothers without periodontitis, only COX-2 (p=0.026) and VEGFR1 (p=0.005)
expressions were significantly increased in those with the disease. Increased COX
2 values were detected in the women with a history of genitourinary infection
(p=0.036), premature rupture of membrane (p=0.012), or drug treatment (p=0.050).
CONCLUSIONS: The etiology of preterm birth and/or low birth weight is
multifactorial and involves consumption habits, social-health factors, and
infectious episodes. These adverse pregnancy outcomes were associated with
periodontitis and the increased placental expression of IL-1beta, COX-2, VEGFR1,
and HSP70.
PMID- 26430763
TI - Oscillatory Positive Expiratory Pressure in Chronic Obstructive Pulmonary
Disease.
AB - Evidence-based guidance for the use of airway clearance techniques (ACT) in
chronic obstructive pulmonary disease (COPD) is lacking in-part because well
established measurements of pulmonary function such as the forced expiratory
volume in 1s (FEV1) are relatively insensitive to ACT. The objective of this
crossover study was to evaluate daily use of an oscillatory positive expiratory
pressure (oPEP) device for 21-28 days in COPD patients who were self-identified
as sputum-producers or non-sputum-producers. COPD volunteers provided written
informed consent to daily oPEP use in a randomized crossover fashion.
Participants completed baseline, crossover and study-end pulmonary function
tests, St. George's Respiratory Questionnaire (SGRQ), Patient Evaluation
Questionnaire (PEQ), Six-Minute Walk Test and (3)He magnetic resonance imaging
(MRI) for the measurement of ventilation abnormalities using the ventilation
defect percent (VDP). Fourteen COPD patients, self-identified as sputum-producers
and 13 COPD-non-sputum-producers completed the study. Post-oPEP, the PEQ-ease
bringing-up-sputum was improved for sputum-producers (p = 0.005) and non-sputum
producers (p = 0.04), the magnitude of which was greater for sputum-producers (p
= 0.03). There were significant post-oPEP improvements for sputum-producers only
for FVC (p = 0.01), 6MWD (p = 0.04), SGRQ total score (p = 0.01) as well as PEQ
patient-global-assessment (p = 0.02). Clinically relevant post-oPEP improvements
for PEQ-ease-bringing-up-sputum/PEQ-patient-global-assessment/SGRQ/VDP were
observed in 8/7/9/6 of 14 sputum-producers and 2/0/3/3 of 13 non-sputum
producers. The post-oPEP change in (3)He MRI VDP was related to the change in PEQ
ease-bringing-up-sputum (r = 0.65, p = 0.0004) and FEV1 (r = -0.50, p = 0.009).
In COPD patients with chronic sputum production, PEQ and SGRQ scores, FVC and
6MWD improved post-oPEP. FEV1 and PEQ-ease-bringing-up-sputum improvements were
related to improved ventilation providing mechanistic evidence to support oPEP
use in COPD. Clinical Trials # NCT02282189 and NCT02282202.
PMID- 26430762
TI - Identification of Target Genes Involved in Wound Healing Angiogenesis of
Endothelial Cells with the Treatment of a Chinese 2-Herb Formula.
AB - Angiogenesis is vitally important in diabetic wound healing. We had previously
demonstrated that a Chinese 2-herb formula (NF3) significantly stimulated
angiogenesis of HUVEC in wound healing. However, the molecular mechanism has not
yet been elucidated. In line with this, global expression profiling of NF3
treated HUVEC was performed so as to assess the regulatory role of NF3 involved
in the underlying signaling pathways in wound healing angiogenesis. The
microarray results illustrated that different panels of differentially expressed
genes were strictly governed in NF3-treated HUVEC in a time-regulated manner. The
microarray analysis followed by qRT-PCR and western blotting verification of NF3
treated HUVEC at 6 h revealed the involvement of various genes in diverse
biological process, e.g., MAP3K14 in anti-inflammation; SLC5A8 in anti
tumorogenesis; DNAJB7 in protein translation; BIRC5, EPCAM, INSL4, MMP8 and NPR3
in cell proliferation; CXCR7, EPCAM, HAND1 and MMP8 in migration; CXCR7, EPCAM
and MMP8 in tubular formation; and BIRC5, CXCR7, EPCAM, HAND1, MMP8 and UBD in
angiogenesis. After 16 h incubation of NF3, other sets of genes were shown with
differential expression in HUVEC, e.g., IL1RAPL2 and NR1H4 in anti-inflammation;
miR28 in anti-tumorogenesis; GRIN1 and LCN1 in anti-oxidation; EPB41 in
intracellular signal transduction; PRL and TFAP2A in cell proliferation; miR28,
PRL and SCG2 in cell migration; PRL in tubular formation; and miR28, NR1H4 and
PRL in angiogenesis. This study provided concrete scientific evidence in support
of the regulatory role of NF3 on endothelial cells involved in wound healing
angiogenesis.
PMID- 26430764
TI - Mitochondrial Profile and Responses to TGF-beta Ligands in Keratoconus.
AB - PURPOSE: Keratoconus (KC) is a complex corneal dystrophy with multifactorial
etiology. Previous studies have shown evidence of mitochondrial abnormalities in
KC; however, the exact cause of these abnormalities remains unknown. The aim of
this study was to identify if transforming growth factor-beta (TGF-beta) isoforms
play a role in the regulation of mitochondrial proteins in human KC cells (HKC).
MATERIALS AND METHODS: Human corneal fibroblasts (HCF) and HKC were isolated and
cultured for 4 weeks in three different conditions: (a) CONTROL: MEM + 10%FBS,
(b) MEM + 10%FBS + TGF-beta1 and (c) MEM + 10%FBS + TGF-beta3. All samples were
processed for mitochondrial damage analysis using real-time PCR. RESULTS: We
quantified and analyzed 84 mitochondrial and five housekeeping genes in HCFs and
HKCs. Our data showed that when TGF-beta1 and/or TGF-beta3 were compared with
control in HCFs, nine genes were significantly different; however, no genes were
significantly regulated by the TGF-beta isoforms in HKCs. Significant differences
were also seen in seven genes when HFCs were compared with HKCs, in all three
conditions. CONCLUSIONS: Overall, our data support the growing consensus that
mitochondrial dysfunction is a key player in KC disease. These in vitro data show
clear links between mitochondrial function and TGF-beta isoforms, with TGF-beta1
severely disrupting KC-mitochondrial function, while TGF-beta3 maintained it,
thus suggesting that TGF-beta may play a role in KC-disease treatment.
PMID- 26430765
TI - Identification of Pol IV and RDR2-dependent precursors of 24 nt siRNAs guiding de
novo DNA methylation in Arabidopsis.
AB - In Arabidopsis thaliana, abundant 24 nucleotide small interfering RNAs (24 nt
siRNA) guide the cytosine methylation and silencing of transposons and a subset
of genes. 24 nt siRNA biogenesis requires nuclear RNA polymerase IV (Pol IV), RNA
dependent RNA polymerase 2 (RDR2) and DICER-like 3 (DCL3). However, siRNA
precursors are mostly undefined. We identified Pol IV and RDR2-dependent RNAs
(P4R2 RNAs) that accumulate in dcl3 mutants and are diced into 24 nt RNAs by DCL3
in vitro. P4R2 RNAs are mostly 26-45 nt and initiate with a purine adjacent to a
pyrimidine, characteristics shared by Pol IV transcripts generated in vitro. RDR2
terminal transferase activity, also demonstrated in vitro, may account for
occasional non-templated nucleotides at P4R2 RNA 3' termini. The 24 nt siRNAs
primarily correspond to the 5' or 3' ends of P4R2 RNAs, suggesting a model
whereby siRNAs are generated from either end of P4R2 duplexes by single dicing
events.
PMID- 26430766
TI - Rapid cell-free forward engineering of novel genetic ring oscillators.
AB - While complex dynamic biological networks control gene expression in all living
organisms, the forward engineering of comparable synthetic networks remains
challenging. The current paradigm of characterizing synthetic networks in cells
results in lengthy design-build-test cycles, minimal data collection, and poor
quantitative characterization. Cell-free systems are appealing alternative
environments, but it remains questionable whether biological networks behave
similarly in cell-free systems and in cells. We characterized in a cell-free
system the 'repressilator', a three-node synthetic oscillator. We then engineered
novel three, four, and five-gene ring architectures, from characterization of
circuit components to rapid analysis of complete networks. When implemented in
cells, our novel 3-node networks produced population-wide oscillations and 95% of
5-node oscillator cells oscillated for up to 72 hr. Oscillation periods in cells
matched the cell-free system results for all networks tested. An alternate
forward engineering paradigm using cell-free systems can thus accurately capture
cellular behavior.
PMID- 26430767
TI - Endoscopic ultrasound-guided FNA and ProCore biopsy in sampling pancreatic and
intra-abdominal masses.
AB - BACKGROUND: ProCore fine-needle biopsy (FNB) was introduced to improve the
diagnostic yield of endoscopic ultrasound (EUS)-guided fine-needle aspiration
(FNA) sampling. The aim of this study was to evaluate EUS-guided sampling of
intra-abdominal masses and compare the diagnostic utility of conventional EUS-FNA
and ProCore FNB. METHODS: EUS-guided biopsy samples (FNA and/or EchoTip ProCore
FNB) were retrospectively retrieved over the course of 23 months. Clinical
findings, pathology reports, and available histological materials were reviewed.
All cell blocks were reviewed, and their cellularity was scored (range, 0-3).
RESULTS: Fifty-six masses from 58 cases were acquired, and they included 40
pancreatic sites and 16 other intra-abdominal sites. Among the 31 FNB-only cases,
71% were satisfactory, 65% were positive for malignancy at the time of final
diagnosis, and their cell blocks were moderately cellular. For the cases with
both FNB and FNA performed, more FNB samples than FNA samples were satisfactory
(83% vs 76%) and were positive for malignancy (65% vs 48%) at final diagnosis,
and the former had more cellular cell blocks (mean score, 1.58 vs 1.29); however,
the differences were not statistically significant. Significantly more FNB
samples were used for immunostains (48% vs 10%; P = .005). CONCLUSIONS: These
data show that a wide variety of intra-abdominal masses were amenable to sampling
by ProCore FNB. In this subset of cases with prior/concurrent indeterminate FNAs,
FNB showed slightly better diagnostic yield, and had more cellular tissue samples
and more material for ancillary studies than matched FNAs.
PMID- 26430768
TI - Efficacy and safety of biapenem against lower respiratory tract infections in
elderly Chinese patients and optimal dosing regimen based on
pharmacokinetic/pharmacodynamic analysis.
AB - The present study evaluated the efficacy and safety of biapenem in elderly
Chinese patients with lower respiratory tract infections (LRTIs) and proposed
optimal dosage regimen on the basis of pharmacokinetic/pharmacodynamic (PK/PD)
analysis. The clinical efficacy, bacterial eradication and comprehensive
therapeutic effect rates of biapenem were 70.3 (78/111), 68.5 (37/54) and 61.1%
(33/54), respectively. Drug-related adverse reactions were seen in 12.6% of
patients (14/111). The total protein level, Acute Physiology and Chronic Health
Evaluation (APACHE) II score, %fT>MIC, fAUC24/MIC and fCmax/MIC values of
patients had significant impacts (P < 0.05) on clinical and bacteriological
efficacy. However, logistic regression analysis showed that only %fT>MIC
independently influenced comprehensive therapeutic effect (P < 0.01, odds ratio =
1.064). The cut-off value for predicting comprehensive therapeutic effect using
%fT>MIC was 75.0%; the sensitivity and specificity were 87.9 and 85.7%,
respectively. Monte Carlo simulations revealed that the usual dosage regimen (300
mg every 12 hours, 0.5 hour infusion) was considered to be insufficient to obtain
satisfactory therapeutic outcomes against low susceptible pathogens for elderly
Chinese patients with LRTIs (CLcr = 70 ml/min).
PMID- 26430769
TI - Cationic Peptides Facilitate Iron-induced Mutagenesis in Bacteria.
AB - Pseudomonas aeruginosa is the causative agent of chronic respiratory infections
and is an important pathogen of cystic fibrosis patients. Adaptive mutations play
an essential role for antimicrobial resistance and persistence. The factors that
contribute to bacterial mutagenesis in this environment are not clear. Recently
it has been proposed that cationic antimicrobial peptides such as LL-37 could act
as mutagens in P. aeruginosa. Here we provide experimental evidence that
mutagenesis is the product of a joint action of LL-37 and free iron. By
estimating mutation rate, mutant frequencies and assessing mutational spectra in
P. aeruginosa treated either with LL-37, iron or a combination of both we
demonstrate that mutation rate and mutant frequency were increased only when free
iron and LL-37 were present simultaneously. Colistin had the same effect. The
addition of an iron chelator completely abolished this mutagenic effect,
suggesting that LL-37 enables iron to enter the cells resulting in DNA damage by
Fenton reactions. This was also supported by the observation that the mutational
spectrum of the bacteria under LL-37-iron regime showed one of the characteristic
Fenton reaction fingerprints: C to T transitions. Free iron concentration in
nature and within hosts is kept at a very low level, but the situation in
infected lungs of cystic fibrosis patients is different. Intermittent bleeding
and damage to the epithelial cells in lungs may contribute to the release of free
iron that in turn leads to generation of reactive oxygen species and
deterioration of the respiratory tract, making it more susceptible to the
infection.
PMID- 26430770
TI - Characterization of a Novel Dengue Serotype 4 Virus-Specific Neutralizing Epitope
on the Envelope Protein Domain III.
AB - The dengue virus (DENV) envelope protein domain III (ED3) has been suggested to
contain receptor recognition sites and the critical neutralizing epitopes. Up to
date, relatively little work has been done on fine mapping of neutralizing
epitopes on ED3 for DENV4. In this study, a novel mouse type-specific
neutralizing antibody 1G6 against DENV4 was obtained with both prophylactic and
therapeutic effects. The epitope was mapped to residues 387-390 of DENV4 envelope
protein. Furthermore, site-directed mutagenesis assay identified two critical
residues (T388 and H390). The epitope is variable among different DENV serotypes
but is highly conserved among four DENV4 genotypes. Affinity measurement showed
that naturally occurring variations in ED3 outside the epitope region did not
alter the binding of mAb 1G6. These findings expand our understanding of the
interactions between neutralizing antibodies and the DENV4 and may be valuable
for rational design of DENV vaccines and antiviral drugs.
PMID- 26430772
TI - Violence Against Older Women: Activism, Social Justice, and Social Change.
AB - The Older Women's Network (OWN) of New South Wales (NSW) is an activist
organization dedicated to promoting the rights of older women, preventing gender-
and aged-based violence, and working toward social justice and social change. In
2007, the OWN NSW Inc. initiated the Prevention of Violence Against Older Women
Working Party to research and document current knowledge and understanding of
violence against older women; focus public attention on this issue; and bring
about changes in public perceptions, policy, and practice. Presented here is an
overview of the major achievements of the OWN Working Party, including a meta
analysis of three research projects, with their findings, recommendations, and
outcomes. In conclusion, research conducted by activist organizations such as OWN
can make a significant contribution to furthering our understanding of violence
against older women and to policy and practice.
PMID- 26430771
TI - Frequency and Distribution of Refractive Error in Adult Life: Methodology and
Findings of the UK Biobank Study.
AB - PURPOSE: To report the methodology and findings of a large scale investigation of
burden and distribution of refractive error, from a contemporary and ethnically
diverse study of health and disease in adults, in the UK. METHODS: U K Biobank, a
unique contemporary resource for the study of health and disease, recruited more
than half a million people aged 40-69 years. A subsample of 107,452 subjects
undertook an enhanced ophthalmic examination which provided autorefraction data
(a measure of refractive error). Refractive error status was categorised using
the mean spherical equivalent refraction measure. Information on socio
demographic factors (age, gender, ethnicity, educational qualifications and
accommodation tenure) was reported at the time of recruitment by questionnaire
and face-to-face interview. RESULTS: Fifty four percent of participants aged 40
69 years had refractive error. Specifically 27% had myopia (4% high myopia),
which was more common amongst younger people, those of higher socio-economic
status, higher educational attainment, or of White or Chinese ethnicity. The
frequency of hypermetropia increased with age (7% at 40-44 years increasing to
46% at 65-69 years), was higher in women and its severity was associated with
ethnicity (moderate or high hypermetropia at least 30% less likely in non-White
ethnic groups compared to White). CONCLUSIONS: Refractive error is a significant
public health issue for the UK and this study provides contemporary data on
adults for planning services, health economic modelling and monitoring of secular
trends. Further investigation of risk factors is necessary to inform strategies
for prevention. There is scope to do this through the planned longitudinal
extension of the UK Biobank study.
PMID- 26430773
TI - Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper
Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral
Neuropathy.
AB - There are multiple neurological complications of cancer and its treatment. This
study assessed the utility of the novel non-invasive ophthalmic technique of
corneal confocal microscopy in identifying neuropathy in patients with upper
gastrointestinal cancer before and after platinum based chemotherapy. In this
study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer
and 21 healthy control subjects underwent assessment of neuropathy using the
neuropathy disability score, quantitative sensory testing for vibration
perception threshold, warm and cold sensation thresholds, cold and heat induced
pain thresholds, nerve conduction studies and corneal confocal microscopy.
Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04)
and warm sensation (P = 0.03) thresholds with a significantly reduced sural
sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal
nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length
(CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from
presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and
CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the
severity of lymph node involvement. After the 3rd cycle of chemotherapy, there
was no change in any measure of neuropathy, except for a significant increase in
CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in
this cohort of patients with upper gastrointestinal cancer, which was related to
disease severity. Furthermore, the increase in CNFL after the chemotherapy may
indicate nerve regeneration.
PMID- 26430775
TI - Thermal Analysis by Structural Characterization as a Method for Assessing
Heterogeneity in Complex Solid Pharmaceutical Dosage Forms.
AB - Characterizing inter- and intrasample heterogeneity of solid and semisolid
pharmaceutical products is important both for rational design of dosage forms and
subsequent quality control during manufacture; however, most pharmaceutical
products are multicomponent formulations that are challenging in this regard.
Thermal analysis, in particular differential scanning calorimetry, is commonly
used to obtain structural information, such as degree of crystallinity, or
identify the presence of a particular polymorph, but the results are an average
over the whole sample; it cannot directly provide information about the spatial
distribution of phases. This study demonstrates the use of a new thermo-optical
technique, thermal analysis by structural characterization (TASC), that can
provide spatially resolved information on thermal transitions by applying a novel
algorithm to images acquired by hot stage microscopy. We determined that TASC can
be a low cost, relatively rapid method of characterizing heterogeneity and other
aspects of structure. In the examples studied, it was found that high heating
rates enabled screening times of 3-5 min per sample. In addition, this study
demonstrated the higher sensitivity of TASC for detecting the metastable form of
polyethylene glycol (PEG) compared to conventional differential scanning
calorimetry (DSC). This preliminary work suggests that TASC will be a worthwhile
additional tool for characterizing a broad range of materials.
PMID- 26430774
TI - Transient Elastography in End-Stage Renal Disease Patients on Hemodialysis: The
Effect of Net Fluid Withdrawal.
AB - BACKGROUND/AIMS: The impact of volume status on liver stiffness measurement (LSM)
as measured by transient elastography (TE) as in end-stage renal disease (ESRD)
was unclear. We evaluated LSM before and after hemodialysis (HD) and identified
the associated factors if the difference of LSM existed. METHODS: A cross
sectional study was conducted in ESRD patients on regular HD. Subjects underwent
TE and bioelectrical impedance before and after HD. RESULTS: Thirty-six patients
were enrolled. Mean (SD) net fluid withdrawal volume (NFWV) per session was 2.55
(0.9) l. Median (range) pre- and post-HD LSMs were 5.38 (2.8-25.7) and 5.4 (2.8
26) kPa, respectively (p = 0.712). Mean differences of pre- and post-HD LSMs
correlated with NFWV (r = 0.49, 95% CI 0.19-0.71, p = 0.002). CONCLUSION: In ESRD
on regular HD, LSM is not affected by HD. TE can be done before or after HD with
similar results. However, fluid excess at pre-HD can cause inaccurately high LSM.
PMID- 26430776
TI - Vitamin D Deficiency Increases the Risk for Moderate to Severe Disease Activity
in Crohn's Disease Patients in South Africa, Measured by the Harvey Bradshaw
Index.
AB - OBJECTIVE: Vitamin D has immunoregulatory properties and appears to influence
disease outcomes in patients with Crohn's disease (CD). The primary aim of this
study was to evaluate the association between vitamin D status and CD activity in
South Africa. METHODS: In a cross-sectional study performed between September
2011 and January 2013, serum 25-hydroxyvitamin D (25(OH)D) was measured in 186
consecutive patients with CD seen at 2 inflammatory bowel disease (IBD) centers
and 199 healthy controls in the Western Cape, South Africa. Lifestyle and
clinical variables were identified using an investigator-administered
questionnaire, as well as clinical examination and patient case notes. Vitamin D
status was evaluated in 2 ways: <= 20 ng/mL vs >= 21 ng/mL and <= 29 ng/mL vs >=
30 ng/mL. Disease activity was measured by the Harvey Bradshaw Index (HBI).
Various 25(OH)D threshold concentrations for predicting a higher HBI score were
also investigated. RESULTS: On multiple log-binomial regression analysis, higher
HBI scores and not having taken vitamin D supplementation in the 6 months prior
to enrollment were identified as risk factors for vitamin D deficiency in
patients with CD, defined either as <= 20 ng/mL or as <= 29 ng/mL (p < 0.03).
Compared to patients with HBI < 5, those with HBI >= 8 were 2.5 times more likely
to have 25(OH)D concentrations <= 21 ng/mL (prevalence risk [PR] = 2.5; 95%
confidence interval [CI], 1.21-6.30). The risk was similar, though not as high,
when defined as <= 29 ng/mL (PR = 2.0; 95% CI, 1.13-3.51). When vitamin D
deficiency was defined as <20, <30, <40, and <50 ng/mL, the sensitivity and
specificity obtained were 44.9% and 78.8%; 75.5% and 62.4%; 86.7% and 44.7%; and
92.9% and 23.5%, respectively (area under the curve = 0.71; p < 0.0001).
CONCLUSION: Low serum 25(OH)D was associated with increased CD activity in a
South African cohort.
PMID- 26430777
TI - Stanhope Speer, Physician and Alpinist: In 1853, First to Describe Mountain
Sickness?
AB - In 1853, Stanhope Templeman Speer published a two-part paper in The Association
Medical Journal on Mountain Sickness. Speer was a physician who had worked at the
Brompton Hospital for Chest Diseases in London and had been Professor of Medicine
in Dublin. He was also an Alpine climber and had made the first ascent of one of
the Wetterhorn peaks. His article ran to ten and a half pages in the Journal and
to 50 pages in a reprint. It consists of anecdotal accounts of symptoms suffered
at altitude from the literature and from his own experiences in the European
Alps. He asks three pertinent questions. Is there a condition of mountain
sickness? Are these symptoms felt by all persons alike and at the same height?
What are the causes, and whence the explanation of such phenomena? In the course
of the article, he answers the first two questions but, like us, 162 years later,
is unable to answer the third. This article seeks to present Speer's original
work and such facts about his life as I have been able to discover.
PMID- 26430778
TI - Challenge of mimicking the influences of the cellular environment on RNA
structure by PEG-induced macromolecular crowding.
AB - There are large differences between the cellular environment and the conditions
widely used to study RNA in vitro. SHAPE RNA structure probing in Escherichia
coli cells has shown that the cellular environment stabilizes both long-range and
local tertiary interactions in the adenine riboswitch aptamer domain. Synthetic
crowding agents are widely used to understand the forces that stabilize RNA
structure and in efforts to recapitulate the cellular environment under
simplified experimental conditions. Here, we studied the structure and ligand
binding ability of the adenine riboswitch in the presence of the macromolecular
crowding agent, polyethylene glycol (PEG). Ethylene glycol and low-molecular mass
PEGs destabilized RNA structure and caused the riboswitch to sample secondary
structures different from those observed in simple buffered solutions or in
cells. In the presence of larger PEGs, longer-range loop-loop interactions were
more similar to those in cells than in buffer alone, consistent with prior work
showing that larger PEGs stabilize compact RNA states. Ligand affinity was
weakened by low-molecular mass PEGs but increased with high-molecular mass PEGs,
indicating that PEG cosolvents exert complex chemical and steric effects on RNA
structure. Regardless of polymer size, however, nucleotide-resolution structural
characteristics observed in cells were not recapitulated in PEG solutions. Our
results reveal that the cellular environment is difficult to recapitulate in
vitro; mimicking the cellular state will likely require a combination of crowding
agents and other chemical species.
PMID- 26430779
TI - The Introduction of Human Heme Oxygenase-1 and Soluble Tumor Necrosis Factor
alpha Receptor Type I With Human IgG1 Fc in Porcine Islets Prolongs Islet
Xenograft Survival in Humanized Mice.
AB - Apoptosis during engraftment and inflammation induce poor islet xenograft
survival. We aimed to determine whether overexpression of human heme oxygenase-1
(HO-1) or soluble tumor necrosis factor-alpha receptor type I with human IgG1 Fc
(sTNF-alphaR-Fc) in porcine islets could improve islet xenograft survival. Adult
porcine islets were transduced with adenovirus containing human HO-1, sTNF-alphaR
Fc, sTNF-alphaR-Fc/HO-1 or green fluorescent protein (control). Humanized mice
were generated by injecting human cord blood-derived CD34(+) stem cells into NOD
scid-IL-2Rgamma(null) mice. Both HO-1 and sTNF-alphaR-Fc reduced islet apoptosis
under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction
without compromising insulin secretion. Introduction of either gene into islets
prolonged islet xenograft survival in pig-to-humanized mice transplantation. The
sTNF-alphaR-Fc/HO-1 group showed the best glucose tolerance. Target genes were
successfully expressed in islet xenografts. Perigraft infiltration of macrophages
and T cells was suppressed with decreased expression of RANTES, tumor necrosis
factor-alpha and IL-6 in treatment groups; however, frequency of pig-specific
interferon-gamma-producing T cells was not decreased, and humoral response was
not significant in any group. Early apoptosis of islet cells was suppressed in
the treatment groups. In conclusion, overexpression of HO-1 or sTNF-alphaR-Fc in
porcine islets improved islet xenograft survival by suppressing both apoptosis
and inflammation. HO-1 or sTNF-alphaR-Fc transgenic pigs have potential for islet
xenotransplantation.
PMID- 26430780
TI - Oxygenation of Organoboronic Acids by a Nonheme Iron(II) Complex: Mimicking
Boronic Acid Monooxygenase Activity.
AB - Phenolic compounds are important intermediates in the bacterial biodegradation of
aromatic compounds in the soil. An Arthrobacter sp. strain has been shown to
exhibit boronic acid monooxygenase activity through the conversion of different
substituted phenylboronic acids to the corresponding phenols using dioxygen.
While a number of methods have been reported to cleave the C-B bonds of
organoboronic acids, there is no report on biomimetic iron complex exhibiting
this activity using dioxygen as the oxidant. In that direction, we have
investigated the reactivity of a nucleophilic iron-oxygen oxidant, generated upon
oxidative decarboxylation of an iron(II)-benzilate complex
[(Tp(Ph2))Fe(II)(benzilate)] (Tp(Ph2) = hydrotris(3,5-diphenyl-pyrazol-1
yl)borate), toward organoboronic acids. The oxidant converts different
aryl/alkylboronic acids to the corresponding oxygenated products with the
incorporation of one oxygen atom from dioxygen. This method represents an
efficient protocol for the oxygenation of boronic acids with dioxygen as the
terminal oxidant.
PMID- 26430781
TI - Interleukin-12 Immunomodulation Delays the Onset of Lethal Peritoneal Disease of
Ovarian Cancer.
AB - The omental fat band (OFB) is the predominant site for metastatic seeding of
ovarian cancer. Previously, we highlighted the influx and accumulation of
neutrophils and macrophages in the OFB following syngeneic ovarian cancer cell
seeding as an important factor in the development of a protumorigenic cascade.
Here we investigated localized immunomodulation as a means of promoting a
successful protective response. As an important TH1-type immunomodulator,
interleukin (IL)-12 has previously been investigated clinically as an anticancer
therapeutic. However, systemic IL-12 administration was associated with serious
side effects, galvanizing the development of immune or accessory cells engineered
to express secreted or membrane-bound IL-12 (mbIL-12). Using an mbIL-12
expressing cell variant, we demonstrate that localized IL-12 in the tumor
microenvironment significantly delays disease development. The mbIL-12-mediated
decrease in tumor burden was associated with a significant reduction in
neutrophil and macrophage infiltration in the OFB, and correlated with a reduced
expression of neutrophil and macrophage chemoattractants (CXCL1, -2, -3 and CCL2,
-7). Vaccination with mitotically impaired tumor cells did not confer protection
against subsequent tumor challenge, indicating that IL-12 did not impact the
immunogenicity of the cancer cells. Our findings are in agreement with previous
reports suggesting that IL-12 may hold promise when delivered in a targeted and
sustained manner to the omental microenvironment. Furthermore, resident cells
within the omental microenvironment may provide a reservoir that can be activated
and mobilized to prevent metastatic seeding within the peritoneum and, therefore,
may be targets for chemotherapeutics.
PMID- 26430782
TI - Proposal of a new staging system for intrahepatic cholangiocarcinoma: Analysis of
surgical patients from a nationwide survey of the Liver Cancer Study Group of
Japan.
AB - BACKGROUND: In the current American Joint Committee on Cancer/International Union
Against Cancer staging system (seventh edition) for intrahepatic
cholangiocarcinoma (ICC), tumor size was excluded, and periductal invasion was
added as a new tumor classification-defining factor. The objective of the current
report was to propose a new staging system for ICC that would be better for
stratifying the survival of patients based on data from the nationwide Liver
Cancer Study Group of Japan database. METHODS: Of 756 patients who underwent
surgical resection for ICC between 2000 and 2005, multivariate analyses of the
clinicopathologic factors of 419 patients who had complete data sets were
performed to elucidate relevant factors for inclusion in a new tumor
classification and staging system. RESULTS: Overall survival data were best
stratified using a cutoff value of 2 cm using a minimal P value approach to
discriminate patient survival. The 5-year survival rate of 15 patients who had
ICC measuring <= 2 cm in greatest dimension without lymph node metastasis or
vascular invasion was 100%, and this cohort was defined as T1. Multivariate
analysis of prognostic factors for 267 patients with lymph node-negative and
metastasis-negative (N0M0) disease indicated that the number of tumors, the
presence arterial invasion, and the presence major biliary invasion were
independent and significant prognostic factors. The proposed new system, which
included tumor number, tumor size, arterial invasion, and major biliary invasion
for tumor classification, provided good stratification of overall patient
survival according to disease stage. Macroscopic periductal invasion was
associated with major biliary invasion and an inferior prognosis. CONCLUSIONS:
The proposed new staging system, which includes a tumor cutoff size of 2 cm and
major biliary invasion, may be useful for assigning patients to surgery.
PMID- 26430783
TI - Patterns of Emphysema Heterogeneity.
AB - BACKGROUND: Although lobar patterns of emphysema heterogeneity are indicative of
optimal target sites for lung volume reduction (LVR) strategies, the presence of
segmental, or sublobar, heterogeneity is often underappreciated. OBJECTIVE: The
aim of this study was to understand lobar and segmental patterns of emphysema
heterogeneity, which may more precisely indicate optimal target sites for LVR
procedures. METHODS: Patterns of emphysema heterogeneity were evaluated in a
representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive
pulmonary disease (COPD) patients from the COPDGene study. High-resolution
computerized tomography analysis software was used to measure tissue destruction
throughout the lungs to compute heterogeneity (>=15% difference in tissue
destruction) between (inter-) and within (intra-) lobes for each patient.
Emphysema tissue destruction was characterized segmentally to define patterns of
heterogeneity. RESULTS: Segmental tissue destruction revealed interlobar
heterogeneity in the left lung (57%) and right lung (52%). Intralobar
heterogeneity was observed in at least one lobe of all patients. No patient
presented true homogeneity at a segmental level. There was true homogeneity
across both lungs in 3% of the cohort when defining heterogeneity as >=30%
difference in tissue destruction. CONCLUSION: Many LVR technologies for treatment
of emphysema have focused on interlobar heterogeneity and target an entire lobe
per procedure. Our observations suggest that a high proportion of patients with
emphysema are affected by interlobar as well as intralobar heterogeneity. These
findings prompt the need for a segmental approach to LVR in the majority of
patients to treat only the most diseased segments and preserve healthier ones.
PMID- 26430785
TI - Knowledge and Perceptions of Highly Pathogenic Avian Influenza (HPAI) among
Poultry Traders in Live Bird Markets in Bali and Lombok, Indonesia.
AB - Highly Pathogenic Avian Influenza (HPAI) has been prevalent in Indonesia since
2003 causing major losses to poultry production and human deaths. Live bird
markets are considered high risk areas due to the density of large numbers of
mixed poultry species of unknown disease status. Understanding trader knowledge
and perceptions of HPAI and biosecurity is critical to reducing transmission risk
and controlling the disease. An interview-administered survey was conducted at 17
live bird markets on the islands of Bali and Lombok in 2008 and 2009. A total of
413 live poultry traders were interviewed. Respondents were mostly male (89%)
with a mean age of 45 years (range: 19-81). The main source of AI information was
TV (78%), although personal communication was also identified to be an important
source, particularly among female traders (60%) and respondents from Bali (43%).
More than half (58%) of live poultry traders interviewed knew that infected birds
can transmit HPAI viruses but were generally unaware that viruses can be
introduced to markets by fomites. Cleaning cages and disposing of sick and dead
birds were recognized as the most important steps to prevent the spread of
disease by respondents. Two thirds (n = 277) of respondents were unwilling to
report sudden or suspicious bird deaths to authorities. Bali vendors perceive
biosecurity to be of higher importance than Lombok vendors and are more willing
to improve biosecurity within markets than traders in Lombok. Collectors and
traders selling large numbers (>214) of poultry, or selling both chickens and
ducks, have better knowledge of HPAI transmission and prevention than vendors or
traders selling smaller quantities or only one species of poultry. Education was
strongly associated with better knowledge but did not influence positive
reporting behavior. Our study reveals that most live poultry traders have limited
knowledge of HPAI transmission and prevention and are generally reluctant to
report bird deaths. Greater efforts are needed to engage local government, market
managers and traders in education and awareness programs, regulatory measures and
incentive mechanisms. Understanding and evaluating the social responses to such
an integrated approach could lead to more effective HPAI prevention and control.
PMID- 26430786
TI - Trans-generational Immune Priming Protects the Eggs Only against Gram-Positive
Bacteria in the Mealworm Beetle.
AB - In many vertebrates and invertebrates, offspring whose mothers have been exposed
to pathogens can exhibit increased levels of immune activity and/or increased
survival to infection. Such phenomena, called "Trans-generational immune priming"
(TGIP) are expected to provide immune protection to the offspring. As the
offspring and their mother may share the same environment, and consequently
similar microbial threats, we expect the immune molecules present in the progeny
to be specific to the microbes that immune challenged the mother. We provide
evidence in the mealworm beetle Tenebrio molitor that the antimicrobial activity
found in the eggs is only active against Gram-positive bacteria, even when
females were exposed to Gram-negative bacteria or fungi. Fungi were weak inducers
of TGIP while we obtained similar levels of anti-Gram-positive activity using
different bacteria for the maternal challenge. Furthermore, we have identified an
antibacterial peptide from the defensin family, the tenecin 1, which spectrum of
activity is exclusively directed toward Gram-positive bacteria as potential
contributor to this antimicrobial activity. We conclude that maternal transfer of
antimicrobial activity in the eggs of T. molitor might have evolved from
persistent Gram-positive bacterial pathogens between insect generations.
PMID- 26430787
TI - Metformin: A Novel but Controversial Drug in Cancer Prevention and Treatment.
AB - Metformin, a biguanide derivative that is widely used for treating type 2
diabetes mellitus, has recently been shown to exert potential anticancer effects.
Many retrospective data and laboratory studies suggest the idea that metformin
has antineoplastic activity, but some other studies reach conflicting
conclusions. Although the precise molecular mechanisms by which metformin affects
various cancers have not been fully elucidated, activation of AMPK-dependent and
AMPK-independent pathways along with energy metabolism aberration, cell cycle
arrest and apoptosis or autophagy induction have emerged as crucial regulators in
this process. In this Review, we describe the role of metformin in the prevention
and treatment of a variety of cancers and summarize the molecular mechanisms that
are currently well documented in the ability of metformin as an anticancer agent.
In addition, the scientific and clinical hurdles regarding the potential role of
metformin in cancer will be discussed.
PMID- 26430784
TI - Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on
APOE epsilon4 and Is Detectable over 18-Months.
AB - High levels of beta-amyloid (Abeta) in the brain and carriage of the APOE
epsilon4 allele have each been linked to cognitive impairment in cognitively
normal (CN) older adults. However, the relationship between these two biomarkers
and cognitive decline is unclear. The aim of this study was to investigate the
relationship between cerebral Abeta level, APOE epsilon4 carrier status, and
cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults
(47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD =
6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the
California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons
indicated that CN older adults with high Abeta who were also APOE epsilon4
carriers demonstrated the most pronounced decline in learning and working memory.
In CN older adults who were APOE epsilon4 non-carriers, high Abeta was unrelated
to cognitive decline in learning and working memory. Carriage of APOE epsilon4 in
CN older adults with low Abeta was associated with a significantly increased rate
of decline in learning and unexpectedly, improved cognitive performance on
measures of verbal episodic memory over 18 months. These results suggest that
Abeta and APOE epsilon4 interact to increase the rate of cognitive decline in CN
older adults and provide further support for the use of Abeta and APOE epsilon4
as biomarkers of early Alzheimer's disease.
PMID- 26430788
TI - Cohort Profile: Growing Up in Wales: The Environments for Healthy Living study.
PMID- 26430789
TI - Cohort Profile: The UK Women's Cohort Study (UKWCS).
PMID- 26430790
TI - Time trends in avoidable cancer mortality in Switzerland and neighbouring
European countries 1996-2010.
AB - QUESTION UNDER STUDY: What are the trends in avoidable cancer mortality in
Switzerland and neighbouring countries? METHODS: Mortality data and population
estimates 1996-2010 were obtained from the Swiss Federal Statistical Office for
Switzerland and the World Health Organization Mortality Database
(http://www.who.int/healthinfo/mortality_data/en/) for Austria, Germany, France
and Italy. Age standardised mortality rates (ASMRs, European standard) per 100
000 person-years were calculated for the population <75 years old by sex for the
following groups of cancer deaths: (1) avoidable through primary prevention; (2)
avoidable through early detection and treatment; (3) avoidable through improved
treatment and medical care; and (4) remaining cancer deaths. To assess time
trends in ASMRs, estimated annual percentage changes (EAPCs) with 95% confidence
intervals (95% CIs) were calculated. RESULTS: In Switzerland and neighbouring
countries cancer mortality in persons <75 years old continuously decreased 1996
2010. Avoidable cancer mortality decreased in all groups of avoidable cancer
deaths in both sexes, with one exception. ASMRs for causes avoidable through
primary prevention increased in females in all countries (in Switzerland from
16.2 to 20.3 per 100 000 person years, EAPC 2.0 [95% CI 1.4 to 2.6]). Compared
with its neighbouring countries, Switzerland showed the lowest rates for all
groups of avoidable cancer mortality in males 2008-2010. CONCLUSION: Overall
avoidable cancer mortality decreased, indicating achievements in cancer care and
related health policies. However, increasing trends in avoidable cancer mortality
through primary prevention for females suggest there is a need in Switzerland and
its European neighbouring countries to improve primary prevention.
PMID- 26430791
TI - Managing Risk in Hodgkin Lymphoma.
AB - Approximately 90% of patients with limited-stage Hodgkin lymphoma are cured. The
cure rate in advanced-stage Hodgkin lymphoma is dramatically better than it once
was, but it is still lower than the rate in patients with limited disease. The
choice of treatment is based on several factors, including symptoms, disease
stage, extent of tumor burden, and prognosis. Positron emission tomography
scanning can be used to assess the patient's stage of disease, which can allow
further individualization of therapy. Traditional frontline treatment options
include doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and, for high
risk patients, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine,
procarbazine, and prednisone (BEACOPP). Autologous stem cell transplantation
cures approximately 50% of patients. The antibody-drug conjugate brentuximab
vedotin is very active in relapsed/refractory Hodgkin lymphoma. Data presented at
the 2014 meeting of the American Society of Hematology (ASH) showed that
brentuximab vedotin was beneficial in several settings, including as
consolidation therapy posttransplant in patients at high risk for relapse, as
first-line salvage therapy in relapsed/refractory Hodgkin lymphoma prior to
autologous hematopoietic cell transplantation, and in combination with
bendamustine in relapsed/refractory disease. The ASH meeting also offered
promising data on novel agents, such as the programmed cell death 1 (PD-1)
inhibitors. In this monograph, 4 experts in the management of Hodgkin lymphoma
discuss various aspects of the disease and provide their perspectives on the new
data presented at the ASH meeting.
PMID- 26430796
TI - Stable Tricyclic Antitubercular Ozonides Derived from Artemisinin.
AB - New, highly stable tricyclic antitubercular ozonides 9 and 10 derived from
artemisinin are reported in 39 and 9% yields, respectively. The ozonide groups of
9 and 10 were found to be stable under strong basic and acidic conditions. The
absolute configuration of ozonides 9 was confirmed by X-ray crystallography.
Ozonide 10 shows promising antitubercular activity against M. tuberculosis H37Ra
and M. tuberculosis H37Rv with MIC values of 0.39 and 3.12 MUg/mL, respectively.
PMID- 26430797
TI - Catalyst-Free Regioselective C-3 Thiocyanation of Imidazopyridines.
AB - A direct and straightforward approach for highly regioselective thiocyanation of
imidazoheterocycles through sp(2) C-H functionalization has been realized at room
temperature. Various C-3 thiocyanated imidazopyridines are formed in moderate to
good yield. The present method exhibits a mild and selective access to a variety
of imidazopyridine derivatives of pharmacological interest.
PMID- 26430798
TI - A vesicular stomatitis virus glycoprotein epitope-incorporated oncolytic
adenovirus overcomes CAR-dependency and shows markedly enhanced cancer cell
killing and suppression of tumor growth.
AB - Utility of traditional oncolytic adenovirus (Ad) has been limited due to low
expression of coxsackie and adenovirus receptor (CAR) in cancer cells which
results in poor infectivity of Ads. Here with an aim of improving the efficiency
of Ad's entry to the cell, we generated a novel tropism-expanded oncolytic Ad
which contains the epitope of vesicular stomatitis virus glycoprotein (VSVG) at
the HI-loop of Ad fiber. We generated 9 variants of oncolytic Ads with varying
linkers and partial deletion to the fiber. Only one VSVG epitope-incorporated
variant, RdB-1L-VSVG, which contains 1 linker and no deletion to fiber, was
produced efficiently. Production of 3-dimensionaly stable fiber in RdB-1L-VSVG
was confirmed by immunoblot analysis. RdB-1L-VSVG shows a remarkable improvement
in cytotoxicity and total viral yield in cancer cells. RdB-1L-VSVG demonstrates
enhanced cytotoxicity in cancer cells with subdued CAR-expression as it can be
internalized by an alternate pathway. Competition assays with a CAR-specific
antibody (Ab) or VSVG receptor, phosphatidyl serine (PS), reveals that cell
internalization of RdB-1L-VSVG is mediated by both CAR and PS. Furthermore,
treatment with RdB-1L-VSVG significantly enhanced anti-tumor effect in vivo.
These studies demonstrate that the strategy to expand oncolytic Ad tropism may
significantly improve therapeutic profile for cancer treatment.
PMID- 26430799
TI - Polystyrene Nanofiber Materials for Visible-Light-Driven Dual Antibacterial
Action via Simultaneous Photogeneration of NO and O2((1)Deltag).
AB - This contribution reports on the preparation, characterization, and biological
evaluation of electrospun polystyrene nanofiber materials engineered with a
covalently grafted NO photodonor and ionically entangled tetracationic porphyrin
and phthalocyanine photosensitizers. These photofunctional materials exhibit an
effective and simultaneous photogeneration of two antibacterial species such as
nitric oxide (NO) and singlet oxygen, O2((1)Deltag) under illumination with
visible light, as demonstrated by their direct detection using amperometric and
time-resolved spectroscopic techniques. Dual-mode photoantibacterial action is
demonstrated by antibacterial tests carried out on Escherichia coli.
PMID- 26430800
TI - Academic Research Partnerships for Long-Term Care: The Time Has Come.
PMID- 26430801
TI - Dynamic orientation transition of the lyotropic lamellar phase at high shear
rates.
AB - The dynamic orientation behavior of the lamellar phase of a triblock copolymer is
studied in a wide range of shear rates as a function of solvent composition. We
find that various phases can be induced by increasing the shear rate. At low
shear rates, the onion phase forms from planar lamellae with many defects. A
further increase of the shear rate caused the onion structure to break down, and
the lamellar phase recovers with fewer defects. Finally, the transition of the
orientation from parallel to perpendicular is observed at high shear rates. In
the orientation transition at high shear rates, a stable intermediate structure,
to our knowledge, is found for the first time. We also find that the critical
shear stress of the rupture of the onion phase coincides with the orientation
transition. The consistency of the critical shear stress suggests that all
orientation transitions at a high shear rate are dominated by a mechanical
balance between the applied viscous stress and the internal relaxation mode of
the lamellae.
PMID- 26430802
TI - Alternative Splicing QTLs in European and African Populations.
AB - With the advent of RNA-sequencing technology, we can detect different types of
alternative splicing and determine how DNA variation regulates splicing. However,
given the short read lengths used in most population-based RNA-sequencing
experiments, quantifying transcripts accurately remains a challenge. Here we
present a method, Altrans, for discovery of alternative splicing quantitative
trait loci (asQTLs). To assess the performance of Altrans, we compared it to
Cufflinks and MISO in simulations and Cufflinks for asQTL discovery. Simulations
show that in the presence of unannotated transcripts, Altrans performs better in
quantifications than Cufflinks and MISO. We have applied Altrans and Cufflinks to
the Geuvadis dataset, which comprises samples from European and African
populations, and discovered (FDR = 1%) 1,427 and 166 asQTLs with Altrans and
1,737 and 304 asQTLs with Cufflinks for Europeans and Africans, respectively. We
show that, by discovering a set of asQTLs in a smaller subset of European samples
and replicating these in the remaining larger subset of Europeans, both methods
achieve similar replication levels (95% for both methods). We find many Altrans
specific asQTLs, which replicate to a high degree (93%). This is mainly due to
junctions absent from the annotations and hence not tested with Cufflinks. The
asQTLs are significantly enriched for biochemically active regions of the genome,
functional marks, and variants in splicing regions, highlighting their biological
relevance. We present an approach for discovering asQTLs that is a more direct
assessment of splicing compared to other methods and is complementary to other
transcript quantification methods.
PMID- 26430804
TI - Imputation of KIR Types from SNP Variation Data.
AB - Large population studies of immune system genes are essential for characterizing
their role in diseases, including autoimmune conditions. Of key interest are a
group of genes encoding the killer cell immunoglobulin-like receptors (KIRs),
which have known and hypothesized roles in autoimmune diseases, resistance to
viruses, reproductive conditions, and cancer. These genes are highly polymorphic,
which makes typing expensive and time consuming. Consequently, despite their
importance, KIRs have been little studied in large cohorts. Statistical
imputation methods developed for other complex loci (e.g., human leukocyte
antigen [HLA]) on the basis of SNP data provide an inexpensive high-throughput
alternative to direct laboratory typing of these loci and have enabled important
findings and insights for many diseases. We present KIR*IMP, a method for
imputation of KIR copy number. We show that KIR*IMP is highly accurate and thus
allows the study of KIRs in large cohorts and enables detailed investigation of
the role of KIRs in human disease.
PMID- 26430806
TI - Live-birth rate in euthyroid women with recurrent miscarriage and thyroid
peroxidase antibodies.
AB - Thyroid autoimmunity with normal thyroid function is associated with recurrent
miscarriage (RM), but the association with live birth is less clear. Therefore,
we determined the association between thyroid peroxidase antibodies (TPO-Ab) and
live-birth rate (LBR) in a retrospective cohort of euthyroid women with
unexplained RM. We included 202 women of which 28 were TPO-Ab positive (13.9%)
and 174 were TPO-Ab negative. TPO-Ab positive women (n = 10) without
levothyroxine treatment had a lower LBR (29%) compared to TPO-Ab negative women
(51%) (HR 0.23, 0.07-0.72, p = 0.012). The LBR in women with TPO-Ab receiving
levothyroxine was not different compared women without TPO-Ab (60% versus 51%, p
= 0.50). In conclusion, TPO-Ab are associated with a lower LBR in euthyroid women
with unexplained RM and these women may benefit from treatment with
levothyroxine.
PMID- 26430807
TI - Gut-derived lymphocyte recruitment to liver and induce liver injury in non
alcoholic fatty liver disease mouse model.
AB - BACKGROUND AND AIM: Most studies focus on gut-derived factors like microbiota and
its products and how they contribute to non-alcoholic fatty liver disease (NAFLD)
progression. This study investigated whether the gut-derived lymphocytes could
migrate to the liver and induce liver injury in NAFLD. METHODS: A high-fat diet
induced an NAFLD mouse model, and lymphocytes were labeled with 1,1-dioctadecyl
3,3,3,3 tetramethylindotricarbocyanine iodide and carboxy-fluorescein
succinimidyl ester, respectively, and intravenously injected to mice to monitor
lymphocyte migration. RESULTS: Adoptive transfer model results indicated that
compared with lymphocytes from the spleen, bone marrow and thymus of NAFLD donor
mice, mesenteric lymph nodes (MLN) cells from NAFLD donor mice predominately
accumulated in the livers of NAFLD recipient mice. The frequencies of central
memory CD4(+) T and CD8(+) T cells in livers of NAFLD mice were significantly
increased; however, the activated T cells were not significantly altered. After
adoptively transferred MLN cells, the frequencies of the activated CD4(+) T and
CD8(+) T cells increased in livers of NAFLD recipient mice. By contrast, the
frequencies of central memory and naive CD4(+) T and CD8(+) T cells decreased.
MLN cells also induced liver injury in NAFLD recipient mice, as reflected by
elevated serum alanine aminotransferase and glutamic oxaloacetic transaminase
serums. Moreover, the chemotaxis assay showed that CCL5 mediated the MLN cell
migration to the liver. Also, blocking the CCL5 inhibited MLN cell migration to
the liver in vitro. CONCLUSIONS: Gut-derived lymphocytes from NAFLD mice could
migrate to the liver and induce liver injury and hepatic CD4(+) T and CD8(+) T
cells activation. The migration was associated with the upregulation of CCL5 in
the liver.
PMID- 26430808
TI - Next-Generation Sequencing of a Cohort of Pulmonary Large Cell Carcinomas
Reclassified by World Health Organization 2015 Criteria.
AB - CONTEXT: The classification of pulmonary large cell carcinoma has undergone a
major revision with the recent World Health Organization (WHO) 2015
Classification. Many large cell carcinomas are now reassigned to either
adenocarcinoma with solid pattern or nonkeratinizing squamous cell carcinoma
based on immunopositivity for adenocarcinoma markers or squamous cell carcinoma
markers, respectively. Large cell carcinomas that are negative for adenocarcinoma
and squamous cell carcinoma immunomarkers are now classified as large cell
carcinoma with null immunohistochemical features (LCC-N). Although a few studies
investigated the mutation profile of large cell carcinomas grouped by immunostain
profile before the publication of the new WHO classification, investigation of
tumors previously diagnosed as large cell carcinoma and reclassified according to
the 2015 WHO classification has not, to our knowledge, been reported. OBJECTIVE:
To determine the mutation profiles of pulmonary large cell carcinomas
reclassified by WHO 2015 criteria. DESIGN: Archival cases of non-small cell lung
carcinoma with large cell carcinoma morphology (n = 17) were reclassified
according to 2015 WHO criteria. To determine mutation profile, we employed Ion
Torrent (Life Technologies, Carlsbad, California)-based next-generation
sequencing (50 genes; more than 2800 mutations) in addition to real-time
quantitative reverse transcription polymerase chain reaction for ALK
translocation detection. RESULTS: Two of 17 cases (12%) were reclassified as LCC
N, and both had mutations-BRAF D594N in one case and KRAS G12C in the other case.
Seven of 17 cases (41%) were reclassified in the adenocarcinoma with solid
pattern group, which showed one KRAS G12C and one EGFR E709K + G719C double
mutation in addition to mutations in TP53. Eight of 17 cases (47%) were
reclassified in the nonkeratinizing squamous cell carcinoma group, which showed
mutations in PIK3CA, CDKN2A, and TP53. No ALK translocations or amplifications
were detected. CONCLUSIONS: The adenocarcinoma with solid pattern group showed
mutations typical of adenocarcinoma, whereas the nonkeratinizing squamous cell
carcinoma group showed mutations typical of squamous cell carcinoma. Both LCC-N
cases had mutations associated with adenocarcinoma, supporting the hypothesis
that LCC-N is related to adenocarcinoma.
PMID- 26430805
TI - How the SAC gets the axe: Integrating kinetochore microtubule attachments with
spindle assembly checkpoint signaling.
AB - Mitosis entails the bona fide segregation of duplicated chromosomes. This process
is accomplished by the attachment of kinetochores on chromosomes to microtubules
(MTs) of the mitotic spindle. Once the appropriate attachment is achieved, the
spindle assembly checkpoint (SAC) that delays the premature onset of anaphase
needs to be silenced for the cell to proceed to anaphase and cytokinesis.
Therefore, while it is imperative to preserve the SAC when kinetochores are
unattached, it is of paramount importance that SAC components are removed post
kinetochore microtubule (kMT) attachment. Precise knowledge of how kMT
attachments trigger the removal of SAC components from kinetochores or how the
checkpoint proteins feedback in to the attachment machinery remains elusive. This
review aims to describe the recent advances that provide an insight into the
interplay of molecular events that coordinate and regulate the SAC activity in
response to kMT attachment during cell division.
PMID- 26430809
TI - Validation of the Lung Subtyping Panel in Multiple Fresh-Frozen and Formalin
Fixed, Paraffin-Embedded Lung Tumor Gene Expression Data Sets.
AB - Context .- A histologic classification of lung cancer subtypes is essential in
guiding therapeutic management. Objective .- To complement morphology-based
classification of lung tumors, a previously developed lung subtyping panel (LSP)
of 57 genes was tested using multiple public fresh-frozen gene-expression data
sets and a prospectively collected set of formalin-fixed, paraffin-embedded lung
tumor samples. Design .- The LSP gene-expression signature was evaluated in
multiple lung cancer gene-expression data sets totaling 2177 patients collected
from 4 platforms: Illumina RNAseq (San Diego, California), Agilent (Santa Clara,
California) and Affymetrix (Santa Clara) microarrays, and quantitative reverse
transcription-polymerase chain reaction. Gene centroids were calculated for each
of 3 genomic-defined subtypes: adenocarcinoma, squamous cell carcinoma, and
neuroendocrine, the latter of which encompassed both small cell carcinoma and
carcinoid. Classification by LSP into 3 subtypes was evaluated in both fresh
frozen and formalin-fixed, paraffin-embedded tumor samples, and agreement with
the original morphology-based diagnosis was determined. Results .- The LSP-based
classifications demonstrated overall agreement with the original clinical
diagnosis ranging from 78% (251 of 322) to 91% (492 of 538 and 869 of 951) in the
fresh-frozen public data sets and 84% (65 of 77) in the formalin-fixed, paraffin
embedded data set. The LSP performance was independent of tissue-preservation
method and gene-expression platform. Secondary, blinded pathology review of
formalin-fixed, paraffin-embedded samples demonstrated concordance of 82% (63 of
77) with the original morphology diagnosis. Conclusions .- The LSP gene
expression signature is a reproducible and objective method for classifying lung
tumors and demonstrates good concordance with morphology-based classification
across multiple data sets. The LSP panel can supplement morphologic assessment of
lung cancers, particularly when classification by standard methods is
challenging.
PMID- 26430810
TI - Employer Expectations for Newly Trained Pathologists: Report of a Survey From the
Graduate Medical Education Committee of the College of American Pathologists.
AB - CONTEXT: -Multiple sources have identified challenges that training programs face
in preparing graduates for the "real world" practice of pathology, and many
training programs have sought to decrease the gap between skills acquired during
training and those required in practice. However, there exists the possibility
that some of the difficulty experienced by newly trained pathologists and
employers might arise from differences between employer expectations of new hires
and what applicants expect from their first job. OBJECTIVE: -To define the
constellation of skills and attributes employers prioritize when hiring newly
trained pathologists. DESIGN: -A survey of fellows of the College of American
Pathologists in practice for 5 or more years in the United States was
administered and the results were analyzed. RESULTS: -A total of 630 pathologists
who were responsible for hiring a new-in-practice pathologist completed the
survey. Regardless of practice setting, certain skills and attributes were rated
critically important in new hires, including ethics/integrity, work ethic, and
professionalism. Seventy-one percent reported having some difficulty hiring entry
level pathologists and cited inadequate training/experience during residency, and
applicants having unrealistic expectations regarding work load/hours as the most
common reasons. CONCLUSIONS: -Prospective employers not only expect well
developed diagnostic skills in their job applicants, but also require evidence of
a strong work ethic and outstanding professionalism. Successful applicants must
display willingness to assume responsibilities and flexibility regarding existing
and new responsibilities. A secondary but important finding of this survey was
that most jobs are garnered through word-of-mouth recommendations; therefore, it
is crucial for pathologists-in-training to hone their networking skills.
PMID- 26430811
TI - RAS mutations - for better or for worse in multiple myeloma?
PMID- 26430812
TI - Two-tiered subdivision of atypia on urine cytology can improve patient follow-up
and optimize the utility of UroVysion.
AB - BACKGROUND: The annual incidence of urothelial carcinoma continues to increase,
and it is projected that greater than 70,000 new cases will occur in the year
2015. However, as much as 23% of cytologic specimens will demonstrate some degree
of atypia without meeting the criteria for urothelial carcinoma and thus will be
reported as atypical. METHODS: The authors conducted 2 laboratory information
searches and 1 survey. In total, 311 patients who had atypical cytology-biopsy
pairs available were identified from the initial data search. The second data
search identified 942 patients who had fluorescence in situ hybridization (FISH)
results available. RESULTS: There was fair agreement between FISH results and
cytology results (kappa = 0.34; 95% confidence interval, 0.27-0.41). The analysis
did not reveal any benefits of using additional atypical subcategories beyond the
2 suggested in the literature. It was determined that 2 strategies would provide
an optimal balance: standardizing patient management and facilitating the
adoption of universally recognized templates. CONCLUSIONS: When combining
cytology and the 2-tiered atypical classification system with FISH testing, a
marked increase in sensitivity and an accompanying decrease in specificity were
observed compared with either test individually. Thus, highly sensitive FISH
testing may help to identify high-risk patients among those in the group with
uncertain atypical findings.
PMID- 26430813
TI - Nicotine delivery, retention and pharmacokinetics from various electronic
cigarettes.
AB - AIMS: To measure the systemic retention of nicotine, propylene glycol (PG) and
vegetable glycerin (VG) in electronic cigarette (e-cigarette) users, and assess
the abuse liability of e-cigarettes by characterizing nicotine pharmacokinetics.
DESIGN: E-cigarette users recruited over the internet participated in a 1-day
research ward study. Subjects took 15 puffs from their usual brand of e
cigarette. Exhaled breath was trapped in gas-washing bottles and blood was
sampled before and several times after use. SETTING: San Francisco, California,
USA. PARTICIPANTS: Thirteen healthy, experienced adult e-cigarette users (six
females and seven males). MEASUREMENTS: Plasma nicotine was analyzed by gas
chromatography-mass spectrometry (GC-MS/MS) and nicotine, VG and PG in e-liquids
and gas traps were analyzed by LC-MS/MS. Heart rate changes and subjective
effects were assessed. FINDINGS: E-cigarettes delivered an average of 1.33 (0.87
1.79) mg [mean and 95% confidence interval (CI)] of nicotine, and 93.8% of the
inhaled dose, 1.22 (0.80-1.66) was systemically retained. Average maximum plasma
nicotine concentration (Cmax ) was 8.4 (5.4-11.5) ng/ml and time of maximal
concentration (Tmax ) was 2-5 minutes. One participant had Tmax of 30 minutes.
84.4% and 91.7% of VG and PG, respectively, was systemically retained. Heart rate
increased by an average of 8.0 beats per minute after 5 minutes. Withdrawal and
urge to smoke decreased and the e-cigarettes were described as satisfying.
CONCLUSIONS: E-cigarettes can deliver levels of nicotine that are comparable to
or higher than typical tobacco cigarettes, with similar systemic retention.
Although the average maximum plasma nicotine concentration in experienced e
cigarette users appears to be generally lower than what has been reported from
tobacco cigarette use, the shape of the pharmacokinetic curve is similar,
suggesting addictive potential.
PMID- 26430803
TI - Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores.
AB - Polygenic risk scores have shown great promise in predicting complex disease risk
and will become more accurate as training sample sizes increase. The standard
approach for calculating risk scores involves linkage disequilibrium (LD)-based
marker pruning and applying a p value threshold to association statistics, but
this discards information and can reduce predictive accuracy. We introduce
LDpred, a method that infers the posterior mean effect size of each marker by
using a prior on effect sizes and LD information from an external reference
panel. Theory and simulations show that LDpred outperforms the approach of
pruning followed by thresholding, particularly at large sample sizes.
Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large
schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis
dataset. A similar relative improvement in accuracy was observed for three
additional large disease datasets and for non-European schizophrenia samples. The
advantage of LDpred over existing methods will grow as sample sizes increase.
PMID- 26430820
TI - Poster Awards Finalist Abstracts.
PMID- 26430814
TI - Recombinant and epitope-based vaccines on the road to the market and implications
for vaccine design and production.
AB - Novel vaccination approaches based on rational design of B- and T-cell epitopes -
epitope-based vaccines - are making progress in the clinical trial pipeline. The
epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a
next-generation approach that successfully reached phase-III trials, and will
potentially become the first commercial vaccine against a human parasitic
disease. Progress made on methods such as recombinant DNA technology, advanced
cell-culture techniques, immunoinformatics and rational design of immunogens are
driving the development of these novel concepts. Synthetic recombinant proteins
comprising both B- and T-cell epitopes can be efficiently produced through modern
biotechnology and bioprocessing methods, and can enable the induction of large
repertoires of immune specificities. In particular, the inclusion of appropriate
CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit
robust immune responses, as suggested by results coming from HIV-1 clinical
trials. In silico strategies for vaccine design are under active development to
address genetic variation in pathogens and several broadly protective "universal"
influenza and HIV-1 vaccines are currently at different stages of clinical
trials. Other methods focus on improving population coverage in target
populations by rationally considering specificity and prevalence of the HLA
proteins, though a proof-of-concept in humans has not been demonstrated yet.
Overall, we expect immunoinformatics and bioprocessing methods to become a
central part of the next-generation epitope-based vaccine development and
production process.
PMID- 26430819
TI - Virtual Reality-Enhanced Cognitive-Behavioral Therapy for Morbid Obesity: A
Randomized Controlled Study with 1 Year Follow-Up.
AB - It is well known that obesity has a multifactorial etiology, including
biological, environmental, and psychological causes. For this reason, obesity
treatment requires a more integrated approach than the standard behavioral
treatment based on dietary and physical activity only. To test the long-term
efficacy of an enhanced cognitive-behavioral therapy (CBT) of obesity, including
a virtual reality (VR) module aimed at both unlocking the negative memory of the
body and to modify its behavioral and emotional correlates, 163 female morbidly
obese inpatients (body mass index >40) were randomly assigned to three
conditions: a standard behavioral inpatient program (SBP), SBP plus standard CBT,
and SBP plus VR-enhanced CBT. Patients' weight, eating behavior, and body
dissatisfaction were measured at the start and upon completion of the inpatient
program. Weight was assessed also at 1 year follow-up. All measures improved
significantly at discharge from the inpatient program, and no significant
difference was found among the conditions. However, odds ratios showed that
patients in the VR condition had a greater probability of maintaining or
improving weight loss at 1 year follow-up than SBP patients had (48% vs. 11%, p =
0.004) and, to a lesser extent, than CBT patients had (48% vs. 29%, p = 0.08).
Indeed, only the VR-enhanced CBT was effective in further improving weight loss
at 1 year follow-up. On the contrary, participants who received only the
inpatient program regained back, on average, most of the weight they had lost.
Findings support the hypothesis that a VR module addressing the locked negative
memory of the body may enhance the long-term efficacy of standard CBT.
PMID- 26430822
TI - Distinct DNA Damage Spectra Induced by Ionizing Radiation in Normoxic and Hypoxic
Cells.
AB - Ionizing radiation induces more cell death under normoxic conditions than under
hypoxic conditions. This phenomenon, which is known as the oxygen enhancement
effect, occurs primarily because ionizing radiation causes more DNA lesions in
the presence of oxygen than in its absence. However, the roles these lesions play
in terms of cell survival and chromosome damage have not been fully
characterized. We exposed a panel of chicken DT40 mutant cells to ionizing
radiation to categorize the type of lesion induced and the DNA-repair pathway
involved under both normoxic and hypoxic conditions. Among the mutant panel,
RAD54(-/-)/KU70(-/-) cells exhibited the greatest radiosensitivity, which was
found to be significantly higher under normoxic conditions. This indicates that
double-strand breaks (DSBs) were the major cause of cell death and that ionizing
radiation induces more DSBs under normoxic condition. Interestingly, the
sensitivity of the REV3(-/-) cells increased under hypoxic conditions. Indeed,
the REV3(-/-) mutant exhibited a greater number of chromosomal aberrations under
hypoxic conditions than under normoxic conditions. These results suggest that the
Rev3-mediated translesion-synthesis pathway is more critical for cellular
tolerance to ionizing radiation in hypoxic cells than in normoxic cells, and that
more chemically modified DNA might be induced under hypoxic conditions. In this
study, we identify a previously unappreciated radiation-induced pattern of DNA
damage under hypoxic conditions.
PMID- 26430821
TI - A Diet Containing Beta-Hydroxy-Beta-Methylbutyrate, L-Glutamine and L-Arginine
Ameliorates Chemoradiation-Induced Gastrointestinal Injury in Rats.
AB - The aim of this study was to investigate the effects of a specific diet,
containing beta-hydroxy-beta-methylbutyrate, L-glutamine and L-arginine
(HMB/Glu/Arg), on chemoradiation-induced injuries of the rat gastrointestinal
mucosa. Wistar albino rats were divided into 4 groups: control (n = 5); radiation
(n = 14); 5-fluorouracil treatment (5-FU; n = 14); and radiation and 5-FU
treatment (n = 14). Rats were fed either a standard diet or a specific diet (SpD)
containing HMB/Glu/Arg supplementation for 7 days prior to radiation exposure
and/or 5-FU treatment. The irradiated groups were exposed to an 1 Gy dose of 6 MV
x rays delivered to the who-abdominal. The animals receiving 5-FU treatment were
given a 100 mg/kg dose of the drug. In the radiation and 5-FU treatment group,
the 5-FU was administered 30 min prior to irradiation. After irradiation and/or 5
FU treatment, feeding with either the standard rat diet or specific diet
continued as before. All animals were sacrificed on day 4 after irradiation and 5
FU treatment. Data collected included microbiological, histological and
immunohistochemical end points. We found that bacterial colony counts in the ceca
and mesenteric lymph nodes of irradiated rats treated with 5-FU were
significantly lower in the specific diet (SpD) group than in the standard diet
group (P = 0.002-0.05). Morphometrically, gastric, duodenal and colonic mucosal
injuries were less severe in the irradiated animals fed the specific diet, as
well as the 5-FU-treated animals fed the specific diet, compared to the similarly
treated standard diet groups. Apoptosis, measured by TUNEL, revealed
significantly lower numbers of TUNEL positive cells in irradiated animals fed the
specific diet, and irradiated animals treated with 5-FU and fed the specific diet
compared to irradiated animals fed the standard diet, and irradiated animals
treated with 5-FU and fed the standard diet. In the 5-Fu-treated and SpD group,
the extent of apoptosis was significantly lower than that of the 5-Fu-treated and
standard diet group in both the stomach and duodenum (P = 0.0001), but not in the
colon. Apoptosis, measured by caspase 3 staining, was significantly less in all
three organs of the SpD groups. In conclusion, these findings suggest that a diet
supplemented with HMB/Glu/Arg may ameliorate the effect of radiation-induced
gastrointestinal injury, coinciding with reduced bacterial growth.
PMID- 26430823
TI - Charge control of the inverse trans-influence.
AB - The synthesis and characterization of uranium(VI) mono(imido) complexes, by the
oxidation of corresponding uranium(V) species, are presented. These experimental
results, paired with DFT analyses, allow for the comparison of the electronic
structure of uranium(VI) mono(oxo) and mono(imido) ligands within a conserved
ligand framework and demonstrate that the magnitude of the ground state
stabilization derived from the inverse trans-influence (ITI) is governed by the
relative charge localization on the multiply bonded atom or group.
PMID- 26430824
TI - Cytoprotective Effects of a Novel Nrf2 Activator, RS9, in Rhodopsin Pro347Leu
Rabbits.
AB - PURPOSE: Rhodopsin Pro347Leu transgenic rabbits were previously generated as
models of retinitis pigmentosa (RP). While the mechanism underlying the retinal
deterioration in these rabbits remains unresolved, it is likely that oxidative
stress is one of the factors triggering cellular loss. We have recently succeeded
in obtaining a novel activator (RS9) of nuclear factor erythroid 2-related factor
(Nrf2, also known as NFE2L2), which regulates antioxidant transcriptional
factors. The purpose of this study was to investigate whether RS9 delays
progressive retinal degeneration in the transgenic rabbits. METHODS: RS9
microspheres (3 mM, 50 uL) were injected into the vitreous of rhodopsin Pro347Leu
transgenic rabbits at 6 weeks, after which outer nuclear layer (ONL) thickness
was measured by optical coherence tomography. Rabbits were sacrificed at 15
weeks. RESULTS: After intravitreal injection of RS9 microspheres, the
concentration of RS9 in the vitreous was maintained at 1 nM for 2 weeks. At a
concentration of 0.3 mM and 50 uL, RS9 significantly inhibited thinning of the
ONL in transgenic rabbits compared to vehicle-injected transgenic rabbits. In RS9
injected transgenic rabbits, Nrf2-targeted genes had increased significantly, and
levels of interleukin-6 mRNA decreased. CONCLUSIONS: Activation of Nrf2 signaling
has potential as a novel approach for the prevention and treatment of RP, not
only by driving intrinsic antioxidant enzymes, but also by inhibiting
inflammatory responses. Although microspheres were employed in this study, small
implants that release more compounds might be a realistic method for clinical
trials.
PMID- 26430825
TI - Pharmacokinetics of once and twice daily dosing of intravenous tobramycin in
paediatric patients with cystic fibrosis.
AB - The optimal dosing of intravenous tobramycin for treatment of pulmonary
exacerbations in paediatric cystic fibrosis (CF) patients has not been completely
delineated. We performed a retrospective study evaluating the pharmacokinetics
and pharmacodynamics of once daily dosing (ODD) of IV tobramycin compared to
twice daily dosing (TDD). Fifty-nine and 44 patients were included in the ODD and
TDD groups, respectively. Once daily dosing achieved higher Cmax as compared to
TDD (29.5 +/- 11.0 vs 19.0 +/- 4.9, P < 0.001), lower 24 hour AUC (92.8 +/- 28.7
vs 128.5 +/- 34.6, P < 0.001), and greater time that drug concentration was below
the minimum inhibitory concentration (MIC) (13.4 +/- 1.7 vs 3.9 +/- 3.1 hour, P <
0.001). Twice daily dosing failed to achieve goal Cmax:MIC for MICs >1.0 mg/l.
Twice daily dosing may be a viable alternative to ODD in treating organisms with
MICs <= 1.0 mg/l; however, with MICs >1.0 mg/l, ODD is likely necessary to
achieve goal Cmax:MIC ratios.
PMID- 26430826
TI - Effects of Multistrain Probiotic Supplementation on Glycemic and Inflammatory
Indices in Patients with Nonalcoholic Fatty Liver Disease: A Double-Blind
Randomized Clinical Trial.
AB - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a condition defined by
exceeding triglycerides accumulation in the liver. The condition can develop into
fibrosis, cirrhosis, and hepatocellular carcinoma. Considering the ever
increasing prevalence of NAFLD, the aim of the present study was to investigate
the effects of probiotic supplementation on glycemic and inflammatory indices in
patients with NAFLD. METHODS: This randomized clinical trial was conducted on 42
patients with NAFLD who had been referred to a gastroenterology clinic. Subjects
in the intervention and control groups consumed 2 capsules/day probiotic or
placebo, respectively, for 8 weeks. Fasting blood sugar (FBS), insulin, insulin
resistance, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6)
were measured at baseline and at the end of the study. RESULTS: Means of FBS,
insulin, insulin resistance, and IL-6 were significantly different between groups
after intervention (p < 0.05), whereas TNF-alpha was not significantly modified
(p > 0.05). In the probiotic group, insulin, insulin resistance, TNF-alpha, and
IL-6 decreased significantly at the end of the study compared to the beginning of
study. CONCLUSION: Considering the effects of probiotic supplementation on the
reduction of glycemic and inflammatory indices in patients with NAFLD,
consumption of probiotics is recommended as a complementary therapy in these
patients.
PMID- 26430832
TI - Hypoalbuminemia and hypergammaglobulinemia are associated with an increased
infection risk in patients with myeloid malignancies treated with azacitidine. A
3-year monocentric retrospective study.
PMID- 26430833
TI - Did Buddha turn the other cheek too? A comparison of posing biases between Jesus
and Buddha.
AB - People tend to exhibit a leftward bias in posing. Various studies suggest that
posing to the left portrays a stronger emotion, whereas posing to the right
portrays a more neutral emotion. Religions such as Christianity emphasize the
role of strong emotions in religious experience, whereas religions such as
Buddhism emphasize the calming of emotions as being important. In the present
study, we investigated if the emphasis on emotionality of a religion influences
the depiction of their religious figures. Specifically, we coded 484 paintings of
Jesus and Buddha from online art databases for whether the deity exhibited a left
bias, right bias, or central face presentation. The posing biases were analysed
to discover whether paintings of Jesus would more frequently depict a leftward
bias than paintings of Buddha. Jesus is more commonly depicted with a leftward
bias than Buddha, and Buddha is more commonly depicted with a central face
presentation than Jesus. These findings support the idea that the amount of
emotionality that is to be conveyed in artwork influences the whether the subject
is posed with a leftward bias.
PMID- 26430834
TI - Synthesis and Substrate Evaluation of (E)-5-[(3-Selenophene-2-Carboxamido)Prop-1
en-1-yl]-Uridine-5'-O-Triphosphate for RNA Polymerase.
AB - Design, synthesis and T7 RNA polymerase substrate evaluation of (E)-5-[(3
selenophene-2-carboxamido)prop-1-en-1-yl]-uridine-5'-O-triphosphate is reported.
The title compound is shown to be a good substrate for RNA polymerase by RNA
labeling through in vitro transcription. pTRI-plasmid DNA with beta-actin gene
sequence (~300 base pairs) with T7 promoter was used as a template for the in
vitro transcription. Transcribed product is characterized for incorporation by
gel assay and for integrity, full length and size by bioanalyzer. The title
compound will be very useful in biophysical techniques to obtain information on
dynamics and recognition properties in real time as well as 3D structure of
nucleic acids.
PMID- 26430836
TI - Expression of Concern: Dual regeneration of muscle and nerve by intravenous
administration of human amniotic fluid-derived mesenchymal stem cells regulated
by stromal cell-derived factor-1alpha in a sciatic nerve injury model.
PMID- 26430837
TI - Neurosurgical patients' perceptions of the "surgeon+": a qualitative study.
AB - OBJECTIVE: Neurosurgical patients bear a varying degree of anxiety when
confronted with having to undergo surgery or even visit with a neurosurgeon in
consultation. Previous studies have suggested that patient perceptions can
heavily influence the patient-physician encounter. Accordingly, a better
understanding of these perceptions can marshal our knowledge regarding strategies
for improving patient-physician interactions during such an apprehensive time.
The aim of the present study was to qualitatively examine patient values and
preferences for a neurosurgeon who participates in extraclinical activities
(i.e., a "neurosurgeon+") and understand the factors that influence these
perceptions. METHODS: Semistructured face-to-face interviews with 47
neurosurgical patients were conducted. Patients were recruited from the Toronto
Western Hospital neurosurgery clinics for cranial and spinal conditions.
Descriptive summary statistics were used to characterize the study participants.
Family members were encouraged to contribute to the interviews. Interviews were
audio-recorded, transcribed, and subjected to thematic analysis by using open and
axial coding. RESULTS: Patients generally indicated that they want to feel
confident in their neurosurgeon. A number of factors contribute to this
confidence, including a strong positive referral from another physician. Patients
are inclined to search for information pertaining to the qualifications of
neurosurgeons online, and a perception of the neurosurgeon's adeptness given his
or her qualifications is important for patients. Although there were some
differences in patient values between those in the cranial and spinal groups,
overall, neurosurgical patients tend to positively view their neurosurgeon's
involvement in extraclinical duties. CONCLUSIONS: This study details the first
comprehensive clinical qualitative study of patient perceptions of neurosurgeons
and provides a descriptive framework for understanding patient values in this
clinical domain.
PMID- 26430838
TI - Utility of tubular retractors to minimize surgical brain injury in the removal of
deep intraparenchymal lesions: a quantitative analysis of FLAIR hyperintensity
and apparent diffusion coefficient maps.
AB - OBJECTIVE: Brain retraction systems are frequently required to achieve surgical
exposure of deep-seated brain lesions. Spatula-based systems can be associated
with injury to the cortex and deep white matter, particularly adjacent to the
sharp edges, which can result in uneven pressure on the parenchyma over the
course of a long operation. The use of tubular retractor systems has been
proposed as a method to overcome these limitations. There have been no studies
assessing the degree of brain injury associated with the use of tubular
retractors. METHODS :Twenty patients were retrospectively identified at Weill
Cornell Medical College who underwent resection of deep-seated brain lesions
between 2005 and 2014 with the aid of a METRx tubular retractor system. Using the
Brainlab software, pre- and postoperative images were analyzed to assess volume,
depth, extent of resection, and change in postoperative MR FLAIR hyperintensity
and restricted diffusion on diffusion-weighted imaging (DWI). RESULTS: The mean
preoperative tumor volume was 16.25 +/- 17.6 cm(3). Gross-total resection was
achieved in 75%, near-total resection in 10%, and subtotal resection in 15% of
patients. There was a small but not statistically significant increase in average
FLAIR hyperintensity volume by 3.25 +/- 10.51 cm(3) (p = 0.16). The average
postoperative volume of DWI high signal area with restricted diffusion on
apparent diffusion coefficient maps was 8.35 +/- 3.05 cm(3). Assuming that the
volume of restricted diffusion on DWI around tumor was 0 preoperatively, this
represented a statistically significant increase on DWI (p < 0.001). CONCLUSIONS:
Although tubular retractors do not appear to significantly increase FLAIR signal
in the brain, DWI intensity around the retractors can be identified. These data
indicate that although tubular retractors may minimize damage to surrounding
tissues, they still cause cytotoxic edema and cellular damage. Objective
comparison against other retraction methods, as compared by 3D volumetric
analysis or similar methods, will be important in determining the true advantage
of tubular retractor systems.
PMID- 26430839
TI - Retraction: Enhancement of regeneration with glia cell line-derived neurotrophic
factor-transduced human amniotic fluid mesenchymal stem cells after sciatic nerve
crush injury.
PMID- 26430840
TI - Retraction: The effect of exercise on mobilization of hematopoietic progenitor
cells involved in the repair of sciatic nerve crush injury.
PMID- 26430841
TI - Results of wrist extension reconstruction in C5-8 brachial plexus palsy by
transferring the pronator quadratus motor branch to the extensor carpi radialis
brevis muscle.
AB - OBJECT The objective of this study was to report the results of pronator
quadratus (PQ) motor branch transfers to the extensor carpi radialis brevis
(ECRB) motor branch to reconstruct wrist extension in C5-8 root lesions of the
brachial plexus. METHODS Twenty-eight patients, averaging 24 years of age, with
C5-8 root injuries underwent operations an average of 7 months after their
accident. In 19 patients, wrist extension was impossible at baseline, whereas in
9 patients wrist extension was managed by activating thumb and wrist extensors.
When these 9 patients grasped an object, their wrist dropped and grasp strength
was lost. Wrist extension was reconstructed by transferring the PQ motor to the
ECRB motor branch. After surgery, patients were followed for at least 12 months,
with final follow-up an average of 22 months after surgery. RESULTS Successful
reinnervation of the ECRB was demonstrated in 27 of the 28 patients. In 25 of the
patients, wrist extension scored M4, and in 2 it scored M3. CONCLUSIONS In C5-8
root injuries, wrist extension can be predictably reconstructed by transferring
the PQ motor branch to reinnervate the ECRB.
PMID- 26430842
TI - Letter to the Editor: Surgical treatment of VA stenosis in the endovascular era.
PMID- 26430843
TI - Distinct displacements of the optic radiation based on tumor location revealed
using preoperative diffusion tensor imaging.
AB - OBJECT Visual field defects (VFDs) due to optic radiation (OR) injury are a
common complication of temporal lobe surgery. The authors analyzed whether
preoperative visualization of the optic tract would reduce this complication by
influencing the surgeon's decisions about surgical approaches. The authors also
determined whether white matter shifts caused by temporal lobe tumors would
follow predetermined patterns based on the tumor's topography. METHODS One
hundred thirteen patients with intraaxial tumors of the temporal lobe underwent
preoperative diffusion tensor imaging (DTI) fiber tracking. In 54 of those
patients, both pre- and postoperative VFDs were documented using computerized
perimetry. Brainlab's iPlan 2.5 navigation software was used for tumor
reconstruction and fiber visualization after the fusion of DTI studies with their
respective magnetization-prepared rapid gradient-echo (MP-RAGE) images. The
tracking algorithm was as follows: minimum fiber length 100 mm, fractional
anisotropy threshold 0.1. The lateral geniculate body and the calcarine cortex
were employed as tract seeding points. Shifts of the OR caused by tumor were
visualized in comparison with the fiber tracking of the patient's healthy
hemisphere. RESULTS Temporal tumors produced a dislocation of the OR but no
apparent fiber destruction. The shift of white matter tracts followed fixed
patterns dependent on tumor location: Temporolateral tumors resulted in a medial
fiber shift, and thus a lateral transcortical approach is recommended.
Temporopolar tumors led to a posterior shift, always including Meyer's loop;
therefore, a pterional transcortical approach is recommended. Temporomesial
tumors produced a lateral and superior shift; thus, a transsylvian-transcisternal
approach will result in maximum sparing of the fibers. Temporocentric tumors also
induced a lateral fiber shift. For those tumors, a transsylvian-transopercular
approach is recommended. Tumors of the fusiform gyrus generated a superior (and
lateral) shift; consequently, a subtemporal approach is recommended to avoid
white matter injury. In applying the approaches recommended above, new or
worsened VFDs occurred in 4% of the patient cohort. Total neurological and
surgical morbidity were less than 10%. In 90% of patients, gross-total resection
was accomplished. CONCLUSIONS Preoperative visualization of the OR may help in
avoiding postoperative VFDs.
PMID- 26430844
TI - Endoscopic fenestration of intraventricular cerebrospinal fluid cysts: the
contralateral approach.
AB - OBJECTIVE: The endoscopic fenestration of intraventricular CSF cysts has evolved
into a well-accepted treatment modality. However, definition of the optimal
trajectory for endoscopic fenestration may be difficult. Distorted ventricular
anatomy and poor visibility within the cyst due to its contents can make
endoscopic fenestration challenging if approached from the ipsilateral side. In
addition, transcortical approaches can theoretically cause injury to eloquent
cortex, particularly in patients with dominant-sided lesions. The aim of this
study was to examine the value of the contralateral transcortical
transventricular approach in patients with dominant-sided ventricular cysts.
METHODS: During a 5-year period between 2007 and 2011, 31 patients with
intraventricular CSF cysts underwent surgery by the senior author (R.R.).
Fourteen of these patients had cysts located on the dominant side. An image
guided endoscopic cyst fenestration via the contralateral transcortical
transventricular approach was performed in 11 patients. A retrospective chart
review was performed in all these patients to extract data on clinical
presentation, operative technique, and surgical outcome. RESULTS: The most common
presenting symptom was headache, followed by memory deficits and cognitive
deterioration. In all cases CSF cysts were space occupying, with associated
obstructive hydrocephalus in 8 patients. Image-guided endoscopic fenestration was
successfully performed in all cases, with septum pellucidotomy necessary in 6
cases, and endoscopic third ventriculostomy in 1 case for additional aqueductal
occlusion. Postoperative clinical outcome was excellent, with no associated
permanent neurological or neuropsychological morbidity. No recurrent cysts were
observed over a mean follow-up period of 2 years and 3 months. CONCLUSIONS: The
contralateral approach to ventricular cysts can achieve excellent surgical
outcomes while minimizing approach-related trauma to the dominant hemisphere.
Careful case selection is essential to ensure that the contralateral endoscopic
trajectory is the best possible exposure for sufficient cyst fenestration and
restoration of CSF circulation.
PMID- 26430845
TI - Reversal of intraoperative arterial thrombosis with a fibrinolytic agent when
treating large and giant partially thrombosed aneurysms of the middle cerebral
artery.
AB - OBJECTIVE: Thrombosis of the cerebral arteries is one of the complications of
microsurgical operations for partially thrombosed intracranial aneurysms. The
object of this study was to assess the frequency of intraoperative arterial
thrombosis (IAT) during microsurgical treatment of large and giant partially
thrombosed aneurysms of the middle cerebral artery (MCA) and also to assess the
efficacy of the treatment of this complication. MATERIALS: The authors analyzed a
consecutive series of 53 patients who underwent surgery for partially thrombosed
aneurysms of the MCA at the Burdenko Neurosurgical Institute between January 2005
and September 2014. Thirty-two patients had large aneurysms (15-25 mm) and 21 had
giant aneurysms (> 25 mm). Clipping of aneurysms was performed in 47 patients,
trapping was performed in 3, and wrapping was performed in 3. RESULTS: IAT was
diagnosed in 10 patients (18.9%). The authors describe a technique for IAT
reversal involving the injection of modified human recombinant prourokinase (mr
proUK). Of the 7 patients who underwent injection of mr-proUK in the thrombosed
artery, 5 (71.4%) were discharged without any change in neurological status, 1
(14.3%) experienced moderate deterioration (modified Rankin Scale [mRS] score of
2), and 1 (14.3%) experienced severe deterioration (mRS score of 4). Among the 3
patients who had complications and did not receive an injection of mr-proUK, 2
experienced severe deterioration (mRS score of 3 and 4) and 1 had moderate
deterioration (mRS score of 2). CONCLUSIONS: The primary risk factor of
thrombectomy with temporary trapping is thrombosis in the MCA branches. The
injection of a fibrinolytic agent into thrombosed MCA branches is an effective
method for the treatment of IAT.
PMID- 26430846
TI - Live-cell imaging to detect phosphatidylserine externalization in brain
endothelial cells exposed to ionizing radiation: implications for the treatment
of brain arteriovenous malformations.
AB - OBJECT Stereotactic radiosurgery (SRS) is an established intervention for brain
arteriovenous malformations (AVMs). The processes of AVM vessel occlusion after
SRS are poorly understood. To improve SRS efficacy, it is important to understand
the cellular response of blood vessels to radiation. The molecular changes on the
surface of AVM endothelial cells after irradiation may also be used for vascular
targeting. This study investigates radiation-induced externalization of
phosphatidylserine (PS) on endothelial cells using live-cell imaging. METHODS An
immortalized cell line generated from mouse brain endothelium, bEnd.3 cells, was
cultured and irradiated at different radiation doses using a linear accelerator.
PS externalization in the cells was subsequently visualized using polarity
sensitive indicator of viability and apoptosis (pSIVA)-IANBD, a polarity
sensitive probe. Live-cell imaging was used to monitor PS externalization in real
time. The effects of radiation on the cell cycle of bEnd.3 cells were also
examined by flow cytometry. RESULTS Ionizing radiation effects are dose
dependent. Reduction in the cell proliferation rate was observed after exposure
to 5 Gy radiation, whereas higher radiation doses (15 Gy and 25 Gy) totally
inhibited proliferation. In comparison with cells treated with sham radiation,
the irradiated cells showed distinct pseudopodial elongation with little or no
spreading of the cell body. The percentages of pSIVA-positive cells were
significantly higher (p = 0.04) 24 hours after treatment in the cultures that
received 25- and 15-Gy doses of radiation. This effect was sustained until the
end of the experiment (3 days). Radiation at 5 Gy did not induce significant PS
externalization compared with the sham-radiation controls at any time points (p >
0.15). Flow cytometric analysis data indicate that irradiation induced growth
arrest of bEnd.3 cells, with cells accumulating in the G2 phase of the cell
cycle. CONCLUSIONS Ionizing radiation causes remarkable cellular changes in
endothelial cells. Significant PS externalization is induced by radiation at
doses of 15 Gy or higher, concomitant with a block in the cell cycle. Radiation
induced markers/targets may have high discriminating power to be harnessed in
vascular targeting for AVM treatment.
PMID- 26430847
TI - Importance of RNF213 polymorphism on clinical features and long-term outcome in
moyamoya disease.
AB - OBJECT Moyamoya disease (MMD) is an idiopathic cerebrovascular occlusive disorder
prevalent in East Asia. In the pathogenesis of MMD, the important role of genetic
factors is being elucidated, and RNF213 has recently been identified as a
susceptibility gene for MMD. The aim of this retrospective study was to
investigate the RNF213 genotype in patients with MMD and to determine their
genotype-phenotype associations. METHODS The study involved 165 Korean MMD
patients from 155 unrelated families who were diagnosed with MMD at a single
center from 1995 to 2013. Their demographic, radiological, and clinical findings
were evaluated. Direct sequencing of the major RNF213 single nucleotide
polymorphisms was performed. The association of the common RNF213 variant with
MMD risk was evaluated using historical controls for comparison. Correlations
between RNF213 genotype and phenotype were statistically analyzed. RESULTS The
c.14429G>A (p.R4810K) variant was identified in 125 (75.8%) of 165 MMD patients.
Most patients (112) were heterozygous, and 13 patients had 2 copies of the
c.14429G>A variant. A novel heterozygous variant, c.12086A>G (p.Q4029R), was
found in 1 additional patient. The minor allele frequency of the c.14429G>A
variant was significantly higher in the MMD group (138 [41.8%] of 330 patients)
than in the control group (8 [1.36%] of 588 subjects; p < 0.001). The c.14429G>A
(p.R4810K) variant significantly increased the risk of MMD in Korean patients,
with an OR of 52.11 (p < 0.001) compared with controls. Moreover, c.14429G>A
(p.R4810K) genotypes occurred more frequently in patients with a family history
of MMD. The homozygous variant was highly associated with early-onset MMD (age at
onset < 5 years), cerebral infarction at diagnosis, and cognitive impairment in
long-term outcome. CONCLUSIONS The findings indicate that the c.14429G>A
(p.R4810K) allele of RNF213 is strongly associated with Korean patients with MMD.
The homozygous c.14429G>A (p.R4810K) variant is particularly related to early
onset MMD, severe symptomatic manifestations at diagnosis, and poor prognosis.
This genotypic variant may be a useful biomarker for early-onset MMD or unstable
MMD with cerebral infarction, which requires early diagnosis and
revascularization treatment.
PMID- 26430848
TI - Gamma Knife radiosurgery for vestibular schwannomas: evaluation of tumor control
and its predictors in a large patient cohort in The Netherlands.
AB - OBJECT The authors of this study sought to assess tumor control and complication
rates in a large cohort of patients who underwent Gamma Knife radiosurgery (GKRS)
for vestibular schwannoma (VS) and to identify predictors of tumor control.
METHODS The records of 420 patients treated with GKRS for VS with a median
marginal dose of 11 Gy were retrospectively analyzed. Patients with
neurofibromatosis Type 2 or who had undergone treatment for VS previously were
excluded. The authors assessed tumor control and complication rates with chart
review and used the Cox proportional hazards model to identify predictors of
tumor control. Preservation of serviceable hearing, defined as Gardner-Robertson
Class I-II, was evaluated in a subgroup of 71 patients with serviceable hearing
at baseline and with available follow-up audiograms. RESULTS The median VS tumor
volume was 1.4 cm(3), and the median length of follow-up was 5.1 years. Actuarial
5-and 10-year tumor control rates were 91.3% and 84.8%, respectively. Only tumor
volume was a statistically significant predictor of tumor control rate. The tumor
control rate decreased from 94.1% for tumors smaller than 0.5 cm(3) to 80.7% for
tumors larger than 6 cm(3). Thirteen patients (3.1%) had new or increased
permanent trigeminal nerve neuropathy, 4 (1.0%) had new or increased permanent
facial weakness, and 5 (1.2%) exhibited new or increased hydrocephalus requiring
a shunting procedure. Actuarial 3-year and 5-year hearing preservation rates were
65% and 42%, respectively. CONCLUSIONS The 5-year actuarial tumor control rate of
91.3% in this cohort of patients with VS compared slightly unfavorably with the
rates reported in other large studies, but the complication and hearing
preservation rates in this study were similar to those reported previously.
Various factors may contribute to the observed differences in reported outcomes.
These factors include variations in treatment indication and in the definition of
treatment failure, as well as a lack of standardization of terminology and of
evaluation of complications. Last, differences in dosimetric variables may also
be an explanatory factor.
PMID- 26430850
TI - Endoscope-assisted retrosigmoid infralabyrinthine approach to jugular foramen
tumors.
AB - OBJECTIVE: Removal of jugular foramen (JF) tumors usually requires extensive
skull base approaches and is frequently associated with postoperative morbidities
such as lower cranial nerve injury. The endoscope-assisted retrosigmoid
infralabyrinthine approach is a relatively new approach to tumors extending into
the bony canal of the JF. The authors present their experience with this
approach. METHODS: The endoscope-assisted retrosigmoid infralabyrinthine approach
was used in 7 patients, including 5 with schwannomas and 2 with paragangliomas.
The access to the tumor, extent of its removal, postoperative neurological
outcome, and approach-related morbidities were evaluated. RESULTS: Two patients
had a history of previous partial tumor removal, and 1 was treated by
embolization followed by two courses of Gamma Knife radiosurgery. In this latter
patient near-total resection was achieved. Gross-total resection was possible in
the remaining 6 patients. Five patients benefited from endoscopic assistance: in
2 patients it showed a tumor remnant after microscopic tumor removal, while in 3
patients it allowed safe removal of the intraforaminal tumor by visualizing the
surrounding structures. No permanent neurological deficit was observed after the
operation. Two patients presenting with swallowing disturbance had temporary
postoperative worsening that improved later. One patient developed CSF leakage
that was managed with a lumbar drain. CONCLUSIONS: This study shows that the
judicious application of the endoscope-assisted retrosigmoid infralabyrinthine
approach is safe and effective for removal of the schwannomas extending into the
JF and selected paragangliomas without significant luminal invasion of the
sigmoid-jugular system.
PMID- 26430849
TI - Quality of survival the 1st year with glioblastoma: a longitudinal study of
patient-reported quality of life.
AB - OBJECTIVE: By exploring longitudinal patient-reported health-related quality of
life (HRQoL), the authors sought to assess the quality of survival for patients
in the 1st year after diagnosis of glioblastoma. METHODS: Thirty unselected
patients >= 18 years who underwent primary surgery for glioblastoma in the period
2011-2013 were included. Using the generic HRQoL questionnaire EQ-5D 3L, baseline
HRQoL was assessed before surgery and at postoperative follow-up after 1, 2, 4,
6, 8, 10, and 12 months. RESULTS: There was an apparent correlation between
deterioration in HRQoL scores and tumor progression. Patients with permanent
deterioration in HRQoL early after surgery represented a subgroup with rapid
progression and short survival. Both positive and negative changes in HRQoL were
more often seen after surgery than after radio- or chemotherapy. Patients with
gross-total resection (GTR) reported better and more stable HRQoL. In a
multivariable analysis preoperative cognitive symptoms (p = 0.02), preoperative
functional status (p = 0.03), and GTR (p = 0.01) were independent predictors of
quality of survival (area under the curve for EQ-5D 3L index values).
CONCLUSIONS: The results indicate that progression-free survival is not only a
surrogate marker for survival, but also for quality of survival. Quality of
survival seems to be associated with GTR, which adds further support for opting
for extensive resections in glioblastoma patients with good preoperative
functional levels.
PMID- 26430852
TI - Structural, Optical, and Electrical Characterization of Yttrium-Substituted
BiFeO3 Ceramics Prepared by Mechanical Activation.
AB - Ceramics of Bi(1-x)Y(x)FeO3 solid solutions (x = 0.02, 0.07, and 0.10) have been
prepared by mechanical activation followed by sintering. The effect of yttrium
content on the structural, electrical, and optical properties of the materials
has been studied. Thus, single-phase solid solutions with rhombohedral R3c
structure have been achieved for x = 0.02 and 0.07, while for x = 0.10 the main
R3c phase has been detected together with a small amount of the orthorhombic Pbnm
phase. Multiferroic properties of the samples, studied by differential scanning
calorimetry (DSC), showed that both T(N) and T(C) (temperatures of the
antiferromagnetic-paramagnetic and ferroelectric-paraelectric transitions,
respectively) decrease with increasing yttrium content. The nature of the
ferroelectric-paraelectric transition has been studied by temperature-dependent X
ray diffraction (XRD), which revealed rhombohedral R3c to orthorhombic Pbnm phase
transitions for x = 0.07 and 0.10. On the other hand, for x = 0.02 the high
temperature phase was indexed as Pnma. Optical properties of the samples, as
studied by diffuse reflectance spectroscopy, showed low optical band gap that
decreases with increasing yttrium content. Prepared ceramics were highly
insulating at room temperature and electrically homogeneous, as assayed by
impedance spectroscopy, and the conductivity increased with x.
PMID- 26430851
TI - Blood is thicker than booze: Examining the role of familism and gender in alcohol
use and related consequences among Hispanic college students.
AB - The present study evaluated cultural, ethnic, and gender differences in drinking
and alcohol-related problems among Hispanic students. Familism protects against
negative outcomes in Hispanic populations, thus we expected familism to buffer
against alcohol problems. Participants (N = 623; 53% female) completed a battery
of measures. Results suggested that familism was protective against drinking.
Furthermore, alcohol use mediated the association between familism and alcohol
related problems. In sum, understanding that culture plays an important role in
people's behaviors and identifying protective factors is critical to inform
culturally sensitive prevention and intervention efforts.
PMID- 26430853
TI - Radiation-associated sarcoma after recurrent colorectal primary tumor: A complex
surgical case.
AB - Radiation associated sarcoma is a significant consequence of cancer therapy.
Incidence of radiation associated sarcoma correlates with overall radiotherapy
exposure. Prognosis is generally poor with 5 year survival rates lower than that
for spontaneously occurring sarcomas. Surgical management presents many
challenges including having to work in irradiated tissue planes while trying to
achieve negative margins. We present a patient with a rare radiation associated
pelvic sarcoma whose course illustrates the complexity of this problem.
PMID- 26430854
TI - Nature plus nurture: the triggering of multiple sclerosis.
AB - Recent clinical and experimental studies indicate that multiple sclerosis
develops as consequence of a failed interplay between genetic ("nature") and
environmental ("nurture") factors. A large number of risk genes favour an
autoimmune response against the body's own brain matter. New experimental data
indicate that the actual trigger of this attack is however provided by an
interaction of brain-specific immune cells with components of the regular
commensal gut flora, the intestinal microbiota. This concept opens the way for
new therapeutic approaches involving modulation of the microbiota by dietary or
antibiotic regimens.
PMID- 26430855
TI - Bacterial diversity and community composition from seasurface to subseafloor.
AB - We investigated compositional relationships between bacterial communities in the
water column and those in deep-sea sediment at three environmentally distinct
Pacific sites (two in the Equatorial Pacific and one in the North Pacific Gyre).
Through pyrosequencing of the v4-v6 hypervariable regions of the 16S ribosomal
RNA gene, we characterized 450,104 pyrotags representing 29,814 operational
taxonomic units (OTUs, 97% similarity). Hierarchical clustering and non-metric
multidimensional scaling partition the samples into four broad groups, regardless
of geographic location: a photic-zone community, a subphotic community, a shallow
sedimentary community and a subseafloor sedimentary community (?1.5 meters below
seafloor). Abundance-weighted community compositions of water-column samples
exhibit a similar trend with depth at all sites, with successive epipelagic,
mesopelagic, bathypelagic and abyssopelagic communities. Taxonomic richness is
generally highest in the water-column O2 minimum zone and lowest in the
subseafloor sediment. OTUs represented by abundant tags in the subseafloor
sediment are often present but represented by few tags in the water column, and
represented by moderately abundant tags in the shallow sediment. In contrast,
OTUs represented by abundant tags in the water are generally absent from the
subseafloor sediment. These results are consistent with (i) dispersal of marine
sedimentary bacteria via the ocean, and (ii) selection of the subseafloor
sedimentary community from within the community present in shallow sediment.
PMID- 26430857
TI - A Tribute to Dr. Diane Billings.
PMID- 26430856
TI - Discordant temporal development of bacterial phyla and the emergence of core in
the fecal microbiota of young children.
AB - The colonization pattern of intestinal microbiota during childhood may impact
health later in life, but children older than 1 year are poorly studied. We
followed healthy children aged 1-4 years (n=28) for up to 12 months, during which
a synbiotic intervention and occasional antibiotics intake occurred, and compared
them with adults from the same region. Microbiota was quantified with the HITChip
phylogenetic microarray and analyzed with linear mixed effects model and other
statistical approaches. Synbiotic administration increased the stability of
Actinobacteria and antibiotics decreased Clostridium cluster XIVa abundance.
Bacterial diversity did not increase in 1- to 5-year-old children and remained
significantly lower than in adults. Actinobacteria, Bacilli and Clostridium
cluster IV retained child-like abundances, whereas some other groups were
converting to adult-like profiles. Microbiota stability increased, with
Bacteroidetes being the main contributor. The common core of microbiota in
children increased with age from 18 to 25 highly abundant genus-level taxa,
including several butyrate-producing organisms, and developed toward an adult
like composition. In conclusion, intestinal microbiota is not established before
5 years of age and diversity, core microbiota and different taxa are still
developing toward adult-type configuration. Discordant development patterns of
bacterial phyla may reflect physiological development steps in children.
PMID- 26430858
TI - Providing Continuing Education for International Nurses.
AB - In an increasingly globalized world, providing continuing education (CE) for
nurses is becoming a more common opportunity for U.S. educators. It is important
for educators to provide CE programs in a culturally competent and sensitive
environment. The challenges involved include effective communication, appropriate
teaching methodologies, contextually appropriate content, and awareness of
cultural-specific needs and customs.
PMID- 26430859
TI - Pupillometry: Cutting Edge Biometrics for Early Intervention in Increased
Intracranial Pressure.
AB - The pupillometer, a cutting-edge biometric device, is a valuable assessment tool
that can aid in the early detection and prompt treatment of neurological
abnormalities. Pupil assessment is a critical component of the neurological
examination, and manual pupil assessment leaves much room for error. Automated
pupillometry improves the quality and reliability of pupillary and neurological
assessments, ultimately improving patient outcomes.
PMID- 26430860
TI - The Professional Development Educator as a FITness Trainer.
AB - Professional development educators play an important role in advancing leadership
development by ensuring a FIT (Fun and Forgiveness, Intelligence and Integrity,
Teamwork and Transparency) workforce. This article addresses the complementarity
of FIT as an organizing model for leadership development.
PMID- 26430861
TI - The Language of Scholarship: How to Rapidly Locate and Avoid Common APA Errors.
AB - This article is relevant for nurses and nursing students who are writing
scholarly documents for work, school, or publication and who have a basic
understanding of American Psychological Association (APA) style. Common APA
errors on the reference list and in citations within the text are reviewed.
Methods to quickly find and reduce those errors are shared.
PMID- 26430862
TI - Continuing Education in Patient Safety: Massive Open Online Courses as a New
Training Tool.
AB - OBJECTIVES: Describe the use of two massive open online courses designed to
provide education on patient safety. Review follow-up evaluation data from the
courses. DISCLOSURE STATEMENT: Neither the planners nor the authors have any
conflicts of interest to disclose. BACKGROUND: The Nursing School of the
University of Cantabria conducted a training session on patient safety through
two massive open online courses (MOOCs) aimed at the general population and
especially Spanish-speaking health professionals. This study aimed to analyze the
profile of health professionals who have completed the courses, their degree of
satisfaction, and the percentage of completion. METHOD: In this retrospective and
observational study, two MOOCs on clinical safety were created through an online
platform (MiriadaX). Quantitative analysis of the profile of health
professionals, their degree of satisfaction, and the percentage of completion was
performed. RESULTS: A total of 12,400 students were enrolled, and the average
completion rate was 32%. The profile of the average student was female, 37 years
old, college educated, a nurse in a hospital, and interested in the course
because it may be useful for performing her work. Fifty-five percent of students
were very satisfied with the course. CONCLUSION: MOOCs are considered to be
effective and easily accessible, with quality content for professional continuing
education that encourages interdisciplinary work and meeting professionals from
around the world.
PMID- 26430864
TI - From Transition Shock to Competent Practice: Developing Preceptors to Support New
Nurse Transition.
AB - BACKGROUND: It is well known that new graduate nurses (NGRNs) are likely to have
a difficult transition from nursing school into professional practice and often
experience a phenomenon known as transition shock. Evidence suggests using
preceptors as an effective method supporting the NGRNs through this difficult
transition. METHOD: This project evaluated the effectiveness of a structured
preceptor development program by measuring perceptions of transition to practice
and first-year retention of two groups of former graduate nurses-the first
comprising preceptors trained through a preceptor development program, and the
second comprising preceptors who did not participate in structured training.
RESULTS: Graduate nurses who had well-trained preceptors had higher, more
positive perceptions about their ability to render safe and optimal care, as well
as higher first-year retention. CONCLUSION: A structured preceptor-training
program may contribute to an improved transition to practice and improved first
year retention rates of NGRNs.
PMID- 26430865
TI - Baseline Indicators and Implementation Strategies in a Statewide Correctional
Nurse Competencies Program: Mid-Year Report.
AB - BACKGROUND: This 3-year, public-academic workforce development project aimed to
establish indicators for quality correctional nursing care to empirically test
the translation of correctional nursing standards into practical and applied
competencies. METHOD: Approaches to document indicators and achieve
implementation of a correctional nurse competency system include (a) knowledge
transfer and exchange, (b) system mapping, (c) adherence to implementation plan
and strategy, and (d) practice-based action research. RESULTS: Indicators were
established. Twenty-five percent (n = 111) of nurses maintained clinical
credentials beyond the basic requirements; 86% (n = 381) of nurses received
continuing nursing education certificates, 98% (n = 434) of nurses were satisfied
with the program, and 43% (n = 9,052) of inmate/patients were satisfied with
clinical care. Quality ratings of program educators averaged 4.79 on a 5-point
scale. CONCLUSION: Innovation is supported by adding continuous improvement
components to the implementation of a correctional nurse competency system
effort. Team members' consensus decision making enabled them to apply their
domain-specific knowledge to assess the success of the implementation strategy.
PMID- 26430866
TI - Implementation of a Preceptor Training Program.
AB - A residency program in hospitals that use preceptorships is an important strategy
for the retention of new graduate RNs. Preceptors need training to be effective
in their role, and this education involves knowing how to implement the roles of
the preceptor, such as role model, socializer, educator, and evaluator. A large
regional medical center identified the need for a preceptor education program to
improve the preceptor program experience for the preceptor and increase the
retention of newly hired RNs. A preceptor training program was developed, using a
blended approach. The approach included use of online modules of key concepts
related to the roles of the preceptor, followed by a face-to-face class that
reinforced the concepts. Increased knowledge of the preceptor's roles can help
the preceptor work with the preceptee in his or her individual unit and promote
retention of the new graduate RNs as they transition to practice in their first
year of employment.
PMID- 26430867
TI - Engaging Clinical Nurses in Quality Improvement Projects.
AB - Clinical nurses have the knowledge and expertise required to provide efficient
and proficient patient care. Time and knowledge deficits can prevent nurses from
developing and implementing quality improvement or evidence-based practice
projects. This article reviews a process for professional development of clinical
nurses that helped them to define, implement, and analyze quality improvement or
evidence-based practice projects. The purpose of this project was to educate
advanced clinical nurses to manage a change project from inception to completion,
using the Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) Change
Acceleration Process as a framework. One-to-one mentoring and didactic in
services advanced the knowledge, appreciation, and practice of advanced practice
clinicians who completed multiple change projects. The projects facilitated
clinical practice changes, with improved patient outcomes; a unit cultural shift,
with appreciation of quality improvement and evidence-based projects; and
engagement with colleagues. Project outcomes were displayed in poster
presentations at a hospital exposition for knowledge dissemination.
PMID- 26430868
TI - Thyroid carcinoma: epidemiology, histology, and diagnosis.
PMID- 26430869
TI - Local treatment of differentiated thyroid carcinoma.
PMID- 26430870
TI - Targeted therapy for advanced or metastatic differentiated thyroid carcinoma.
PMID- 26430871
TI - New and emerging therapeutic options for thyroid carcinoma: A&A discussion.
PMID- 26430872
TI - Reaction Intermediates Kinetics in Solution Investigated by Electrospray
Ionization Mass Spectrometry: Diaurated Complexes.
AB - A new method to investigate the reaction kinetics of intermediates in solution by
electrospray ionization mass spectrometry is presented. The method, referred to
as delayed reactant labeling, allows investigation of a reaction mixture
containing isotopically labeled and unlabeled reactants with different reaction
times. It is shown that we can extract rate constants for the degradation of
reaction intermediates and investigate the effects of various reaction conditions
on their half-life. This method directly addresses the problem of the relevance
of detected gaseous ions toward the investigated reaction solution. It is
demonstrated for geminally diaurated intermediates formed in the gold mediated
addition of methanol to alkynes. Delayed reactant labeling allows us to directly
link the kinetics of the diaurated intermediates with the overall reaction
kinetics determined by NMR spectroscopy. It is shown that the kinetics of
protodeauration of these intermediates mirrors the kinetics of the addition of
methanol demonstrating they are directly involved in the catalytic cycle.
Formation as well as decomposition of diaurated intermediates can be drastically
slowed down by employing bulky ancillary ligands at the gold catalyst; the
catalytic cycle then proceeds via monoaurated intermediates. The reaction is
investigated for 1-phenylpropyne (Ph-CC-CH3) using [AuCl(PPh3)]/AgSbF6 and
[AuCl(IPr)]/AgSbF6 as model catalysts. Delayed reactant labeling is achieved by
using a combination of CH3OH and CD3OH or Ph-CC-CH3 and Ph-CC-CD3.
PMID- 26430874
TI - NMR Spectra of Glycine Isotopomers in Anisotropic Media: Subtle Chiral
Interactions.
AB - NMR spectra of deuterated glycine-2-(13)C revealed interactions between chiral
anisotropic gelatin and kappa-carrageenan gels and the prochiral and chiral
isotopomers. The (1)H, (2)H and (13)C NMR spectra of mixtures of racemic mono-
and prochiral bis-deuterated glycine-2-(13)C were resolved and well simulated
using distinct dipolar coupling constants DCalphaH and DCalphaD for the
enantiomers and also for the -(13)CalphaD2- group (DC,DA, and DC,DB). The
orientation of the proton or deuteron on the (13)Calpha-atom of glycine was
assigned by analogy with alanine and lactate assuming that the molecular
orientation of glycine isotopomers is the same. The assignment of the prochiral
sites was derived from chiral analogues.
PMID- 26430875
TI - Development of (Trifluoromethyl)zinc Reagent as Trifluoromethyl Anion and
Difluorocarbene Sources.
AB - The trifluoromethylation of carbonyl compounds is accomplished by the stable
(trifluoromethyl)zinc reagent generated and then isolated from CF3I and ZnEt2,
which can be utilized as a trifluoromethyl anion source (CF3(-)). The reaction
proceeds smoothly with diamine as a ligand and ammonium salt as an initiator,
providing the corresponding trifluoromethylated alcohol products. Moreover, the
(trifluoromethyl)zinc reagent can also be employed as a difluorocarbene source
(:CF2) not only for gem-difluoroolefination of carbonyl compounds with phosphine
but also for gem-difluorocyclization of alkenes or alkynes via the thermal
decomposition, respectively.
PMID- 26430873
TI - Targeting MCM2 function as a novel strategy for the treatment of highly malignant
breast tumors.
AB - Highly malignant tumors express high levels of the minichromosome maintenance 2
(MCM2) protein, which is associated with advanced tumor grade, advanced stage,
and poor prognosis. In a previous study, we showed that Friend leukemia virus
(FLV) envelope protein gp70 bound MCM2, impaired its nuclear translocation, and
enhanced DNA-damage-induced apoptosis in FLV-infected hematopoietic cells when
the cells expressed high levels of MCM2. Here, we show that MCM2 is highly
expressed in clinical samples of invasive carcinoma of the breast, especially
triple-negative breast cancer (TNBC), and in cancer stem cell (CSC) marker
positive breast cancer cells. To generate a cancer therapy model using gp70, we
introduced the gp70 protein into the cytoplasm of murine breast cancer cells that
express high levels of MCM2 by conjugating the protein transduction domain (PTD)
of Hph-1 to gp70 (Hph-1-gp70). Hph-1-gp70 was successfully transduced into the
cytoplasm of breast cancer cells. The transduced protein enhanced the DNA damage
induced apoptosis of cancer cells in vitro and in vivo. Therefore, an MCM2
targeted strategy using Hph-1-gp70 treatment to induce DNA damage might be a
successful therapy for highly malignant breast cancers such as TNBC and for the
eradication of CSC-like cells from breast cancer tissue.
PMID- 26430876
TI - Noncovalent Ruthenium(II) Complexes-Single-Walled Carbon Nanotube Composites for
Bimodal Photothermal and Photodynamic Therapy with Near-Infrared Irradiation.
AB - To enhance the efficacy and optimize the treatment of cancers, the integration of
multimodal treatment strategies leading to synergistic effects is a promising
approach. The coassembly of multifunctional agents for systematic therapies has
received considerable interest in cancer treatment. Herein, Ru(II) complex
functionalized single-walled carbon nanotubes (Ru@SWCNTs) are developed as
nanotemplates for bimodal photothermal and two-photon photodynamic therapy (PTT
TPPDT). SWCNTs have the ability to load a great amount of Ru(II) complexes (Ru1
or Ru2) via noncovalent pi-pi interactions. The loaded Ru(II) complexes are
efficiently released by the photothermal effect of irradiation from an 808 nm
diode laser (0.25 W/cm(2)). The released Ru(II) complexes produce singlet oxygen
species ((1)O2) upon two-photon laser irradiation (808 nm, 0.25 W/cm(2)) and can
be used as a two-photon photodynamic therapy (TPPDT) agent. Based on the
combination of photothermal therapy and two-photon photodynamic therapy,
Ru@SWCNTs have greater anticancer efficacies than either PDT using Ru(II)
complexes or PTT using SWCNTs in two-dimensional (2D) cancer cell and three
dimensional (3D) multicellular tumor spheroid (MCTS) models. Furthermore, in vivo
tumor ablation is achieved with excellent treatment efficacy under a diode laser
(808 nm) irradiation at the power density of 0.25 W/cm(2) for 5 min. This study
examines an efficacious bimodal PTT and TPPDT nanoplat form for the development
of cancer therapeutics.
PMID- 26430877
TI - Enzyme-Free Amplification by Nano Sticky Balls for Visual Detection of ssDNA/RNA
Oligonucleotides.
AB - Visual detection of nucleic acids provides simple and rapid screening for
infectious diseases or environmental pathogens. However, sensitivity is the
current bottleneck, which may require enzymatic amplification for targets in low
abundance and make them incompatible with detection at resource-limited sites.
Here we report an enzyme-free amplification that provides a sensitive visual
detection of ssDNA/RNA oligonucleotides on the basis of nano "sticky balls". When
target oligonucleotides are present, magnetic microparticles (MMPs) and gold
nanoparticles (AuNPs) were linked together, allowing the collection of AuNPs
after magnetic attraction. Subsequently, the collected AuNPs, which carry many
oligonucleotides, were used as the sticky balls to link a second pair of MMPs and
polymer microparticles (PMPs). Thus, because the magnetic field can attract the
MMPs as well as the linked PMPs to the sidewall, the reduction of suspended PMPs
yields a change of light transmission visible by the naked eye. Our results
demonstrate that the limit of detection is 10 amol for ssDNAs (228 fM in 45 MUL)
and 75 amol for ssRNAs (1.67 pM in 45 MUL). This method is also compatible with
the serum environment and detection of a microRNA, miR-155, derived from human
breast cancer cells. With significantly improved sensitivity for visual
detection, it provides great potential for point-of-care applications at resource
limited sites.
PMID- 26430878
TI - Synthesis of Fluorine-Containing Phosphodiesterase 10A (PDE10A) Inhibitors and
the In Vivo Evaluation of F-18 Labeled PDE10A PET Tracers in Rodent and Nonhuman
Primate.
AB - A series of fluorine-containing PDE10A inhibitors were designed and synthesized
to improve the metabolic stability of [(11)C]MP-10. Twenty of the 22 new
analogues had high potency and selectivity for PDE10A: 18a-j, 19d-j, 20a-b, and
21b had IC50 values <5 nM for PDE10A. Seven F-18 labeled compounds [(18)F]18a-e,
[(18)F]18g, and [(18)F]20a were radiosynthesized by (18)F-introduction onto the
quinoline rather than the pyrazole moiety of the MP-10 pharmacophore and
performed in vivo evaluation. Biodistribution studies in rats showed ~2-fold
higher activity in the PDE10A-enriched striatum than nontarget brain regions;
this ratio increased from 5 to 30 min postinjection, particularly for [(18)F]18a
d and [(18)F]20a. MicroPET studies of [(18)F]18d and [(18)F]20a in nonhuman
primates provided clear visualization of striatum with suitable equilibrium
kinetics and favorable metabolic stability. These results suggest this strategy
may identify a (18)F-labeled PET tracer for quantifying the levels of PDE10A in
patients with CNS disorders including Huntington's disease and schizophrenia.
PMID- 26430879
TI - Lipopolysaccharide-Induced Differential Expression of miRNAs in Male and Female
Rhipicephalus haemaphysaloides Ticks.
AB - Lipopolysaccharide (LPS) stimulates the innate immune response in arthropods. In
tick vectors, LPS activates expression of immune genes, including those for
antibacterial peptides. miRNAs are 21-24 nt non-coding small RNAs that regulate
target mRNAs at the post-transcriptional level. However, our understanding of
tick innate immunity is limited to a few cellular immune reactions and some
characterized immune molecules. Moreover, there is little information on the
regulation of the immune system in ticks by miRNA. Therefore, this study aimed to
analyze the differential expression of miRNAs in male and female ticks after LPS
injection. LPS was injected into male and female Rhipicephalus haemaphysaloides
ticks to stimulate immune response, with phosphate buffered saline (PBS)-injected
ticks as negative controls. miRNAs from each group were sequenced and analyzed.
In the PBS- and LPS-injected female ticks, 11.46 and 12.82 million reads of 18-30
nt were obtained respectively. There were 13.92 and 15.29 million reads of 18-30
nt obtained in the PBS- and LPS-injected male ticks, respectively. Expression of
miRNAs in male ticks was greater than that in female ticks. There were 955 and
984 conserved miRNA families in the PBS- and LPS-injected female ticks,
respectively, and correspondingly 1684 and 1552 conserved miRNA families in male
ticks. Nine novel miRNAs were detected as common miRNAs in two or more tested
samples. There were 37 known miRNAs up-regulated >10-fold and 33 down-regulated
>10-fold in LPS-injected female ticks; and correspondingly 52 and 59 miRNAs in
male ticks. Differential expression of miRNAs in PBS- and LPS-injected samples
supports their involvement in the regulation of innate immunity. These data
provide an important resource for more detailed functional analysis of miRNAs in
this species.
PMID- 26430880
TI - Characterization of Biofilm Formation in [Pasteurella] pneumotropica and
[Actinobacillus] muris Isolates of Mouse Origin.
AB - [Pasteurella] pneumotropica biotypes Jawetz and Heyl and [Actinobacillus] muris
are the most prevalent Pasteurellaceae species isolated from laboratory mouse.
However, mechanisms contributing to their high prevalence such as the ability to
form biofilms have not been studied yet. In the present investigation we analyze
if these bacterial species can produce biofilms in vitro and investigate whether
proteins, extracellular DNA and polysaccharides are involved in the biofilm
formation and structure by inhibition and dispersal assays using proteinase K,
DNase I and sodium periodate. Finally, the capacity of the biofilms to confer
resistance to antibiotics is examined. We demonstrate that both [P.]
pneumotropica biotypes but not [A.] muris are able to form robust biofilms in
vitro, a phenotype which is widely spread among the field isolates. The biofilm
inhibition and dispersal assays by proteinase and DNase lead to a strong
inhibition in biofilm formation when added at the initiation of the biofilm
formation and dispersed pre-formed [P.] pneumotropica biofilms, revealing thus
that proteins and extracellular DNA are essential in biofilm formation and
structure. Sodium periodate inhibited the bacterial growth when added at the
beginning of the biofilm formation assay, making difficult the assessment of the
role of beta-1,6-linked polysaccharides in the biofilm formation, and had a
biofilm stimulating effect when added on pre-established mature biofilms of [P.]
pneumotropica biotype Heyl and a majority of [P.] pneumotropica biotype Jawetz
strains, suggesting that the presence of beta-1,6-linked polysaccharides on the
bacterial surface might attenuate the biofilm production. Conversely, no effect
or a decrease in the biofilm quantity was observed by biofilm dispersal using
sodium periodate on further biotype Jawetz isolates, suggesting that
polysaccharides might be incorporated in the biofilm structure. We additionally
show that [P.] pneumotropica cells enclosed in biofilms were less sensitive to
treatment with amoxicillin and enrofloxacin than planktonic bacteria. Taken
together, these findings provide a first step in understanding of the biofilm
mechanisms in [P.] pneumotropica, which might contribute to elucidation of
colonization and pathogenesis mechanisms for these obligate inhabitants of the
mouse mucosa.
PMID- 26430881
TI - A Unique Expression of Keratin 14 in a Subset of Trophoblast Cells.
AB - The placenta, a transient organ in human, is essential for pregnancy maintenance
and for fetal growth and development. Trophoblast and stromal cells are the main
cell types present in human placenta. Trophoblast cells are present in different
subtypes depending on their differentiation state and their temporal and spatial
location during pregnancy. The stromal cells are of extraembryonic mesenchymal
origin and are important for villous formation and maintenance. Interestingly,
many pregnancy-related diseases are associated with defect in trophoblast
differentiation and villous integrity. Therefore, it's crucial to specifically
identify each type of placental cells using specific markers. Keratins (CK) are
widely used as marker of epithelial cells, cancer origin identification and in
some cases as marker of stem/progenitor cells. Vimentin is widely used as marker
of mesenchymal cells. The aim of this study is to characterize the presence of
different keratins in human trophoblast cells and vimentin in stromal cells.
Using immunohistochemistry on term placental sections, our results show that
vimentin is solely expressed in stromal-mesenchymal cells while keratins 5, 7, 8,
14 and 19 are expressed in trophoblast cells. Interestingly, all keratins tested,
except for keratin 14, were evenly expressed in all trophoblast cells. Keratin 14
was expressed in a subset of CK7 positive cells. Moreover, the same results were
obtained when using freshly isolated cytotrophoblast cells or BeWo cells. In
conclusion, this study is a crucial step in the advancement of our knowledge in
placental cell type identification and characterization.
PMID- 26430882
TI - Altered Monocyte Phenotype in HIV-1 Infection Tends to Normalize with Integrase
Inhibitor-Based Antiretroviral Therapy.
AB - BACKGROUND: Monocytes are increasingly implicated in the inflammatory
consequences of HIV-1 disease, yet their phenotype following antiretroviral
therapy (ART) initiation is incompletely defined. Here, we define more completely
monocyte phenotype both prior to ART initiation and during 48 weeks of ART.
METHODS: Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained
at baseline (prior to ART initiation) and at weeks 12, 24, and 48 of treatment
from 29 patients participating in ACTG clinical trial A5248, an open label study
of raltegravir/emtricitibine/tenofovir administration. For comparison,
cryopreserved PBMCs were obtained from 15 HIV-1 uninfected donors, each of whom
had at least two cardiovascular risk factors. Thawed samples were stained for
monocyte subset markers (CD14 and CD16), HLA-DR, CCR2, CX3CR1, CD86, CD83, CD40,
CD38, CD36, CD13, and CD163 and examined using flow cytometry. RESULTS: In
untreated HIV-1 infection there were perturbations in monocyte subset phenotypes,
chiefly a higher frequency and density (mean fluorescence intensity-MFI) of HLA
DR (%-p = 0.004, MFI-p = .0005) and CD86 (%-p = 0.012, MFI-p = 0.005) expression
and lower frequency of CCR2 (p = 0.0002) expression on all monocytes, lower CCR2
density on inflammatory monocytes (p = 0.045) when compared to the expression and
density of these markers in controls' monocytes. We also report lower expression
of CX3CR1 (p = 0.014) on patrolling monocytes at baseline, compared to levels
seen in controls. After ART, these perturbations tended to improve, with
decreasing expression and density of HLA-DR and CD86, increasing CCR2 density on
inflammatory monocytes, and increasing expression and density of CX3CR1 on
patrolling monocytes. CONCLUSIONS: In HIV-1 infected patients, ART appears to
attenuate the high levels of activation (HLA-DR, CD86) and to increase expression
of the chemokine receptors CCR2 and CX3CR1 on monocyte populations. Circulating
monocyte phenotypes are altered in untreated infection and tend to normalize with
ART; the role of these cells in the inflammatory environment of HIV-1 infection
warrants further study.
PMID- 26430884
TI - A Fab-Selective Immunoglobulin-Binding Domain from Streptococcal Protein G with
Improved Half-Life Extension Properties.
AB - BACKGROUND: Half-life extension strategies have gained increasing interest to
improve the pharmacokinetic and pharmacodynamic properties of protein
therapeutics. Recently, we established an immunoglobulin-binding domain (IgBD)
from streptococcal protein G (SpGC3) as module for half-life extension. SpGC3 is
capable of binding to the Fc region as well as the CH1 domain of Fab arms under
neutral and acidic conditions. METHODOLOGY/PRINCIPAL FINDINGS: Using site
directed mutagenesis, we generated a Fab-selective mutant (SpGC3Fab) to avoid
possible interference with the FcRn-mediated recycling process and improved its
affinity for mouse and human IgG by site-directed mutagenesis and phage display
selections. In mice, this affinity-improved mutant (SpGC3FabRR) conferred
prolonged plasma half-lives compared with SpGC3Fab when fused to small
recombinant antibody fragments, such as single-chain Fv (scFv) and bispecific
single-chain diabody (scDb). Hence, the SpGC3FabRR domain seems to be a suitable
fusion partner for the half-life extension of small recombinant therapeutics.
CONCLUSIONS/SIGNIFICANCE: The half-life extension properties of SpGC3 can be
retained by restricting binding to the Fab fragment of serum immunoglobulins and
can be improved by increasing binding activity. The modified SpGC3 module should
be suitable to extend the half-life of therapeutic proteins and, thus to improve
therapeutic activity.
PMID- 26430883
TI - Design of a New Type of Compact Chemical Heater for Isothermal Nucleic Acid
Amplification.
AB - Previous chemical heater designs for isothermal nucleic acid amplification have
been based on solid-liquid phase transition, but using this approach, developers
have identified design challenges en route to developing a low-cost, disposable
device. Here, we demonstrate the feasibility of a new heater configuration
suitable for isothermal amplification in which one reactant of an exothermic
reaction is a liquid-gas phase-change material, thereby eliminating the need for
a separate phase-change compartment. This design offers potentially enhanced
performance and energy density compared to other chemical and electric heaters.
PMID- 26430885
TI - Reversing Stimulus Timing in Visual Conditioning Leads to Memories with Opposite
Valence in Drosophila.
AB - Animals need to associate different environmental stimuli with each other
regardless of whether they temporally overlap or not. Drosophila melanogaster
displays olfactory trace conditioning, where an odor is followed by electric
shock reinforcement after a temporal gap, leading to conditioned odor avoidance.
Reversing the stimulus timing in olfactory conditioning results in the reversal
of memory valence such that an odor that follows shock is later on approached
(i.e. relief conditioning). Here, we explored the effects of stimulus timing on
memory in another sensory modality, using a visual conditioning paradigm. We
found that flies form visual memories of opposite valence depending on stimulus
timing and can associate a visual stimulus with reinforcement despite being
presented with a temporal gap. These results suggest that associative memories
with non-overlapping stimuli and the effect of stimulus timing on memory valence
are shared across sensory modalities.
PMID- 26430886
TI - Genotyping by Sequencing for SNP-Based Linkage Map Construction and QTL Analysis
of Chilling Requirement and Bloom Date in Peach [Prunus persica (L.) Batsch].
AB - Low-cost, high throughput genotyping methods are crucial to marker discovery and
marker-assisted breeding efforts, but have not been available for many 'specialty
crops' such as fruit and nut trees. Here we apply the Genotyping-By-Sequencing
(GBS) method developed for cereals to the discovery of single nucleotide
polymorphisms (SNPs) in a peach F2 mapping population. Peach is a genetic and
genomic model within the Rosaceae and will provide a template for the use of this
method with other members of this family. Our F2 mapping population of 57
genotypes segregates for bloom time (BD) and chilling requirement (CR) and we
have extensively phenotyped this population. The population derives from a selfed
F1 progeny of a cross between 'Hakuho' (high CR) and 'UFGold' (low CR). We were
able to successfully employ GBS and the TASSEL GBS pipeline without modification
of the original methodology using the ApeKI restriction enzyme and multiplexing
at an equivalent of 96 samples per Illumina HiSeq 2000 lane. We obtained hundreds
of SNP markers which were then used to construct a genetic linkage map and
identify quantitative trait loci (QTL) for BD and CR.
PMID- 26430889
TI - Correction: A Differential Effect of E. coli Toxin-Antitoxin Systems on Cell
Death in Liquid Media and Biofilm Formation.
PMID- 26430887
TI - Risk Knowledge in Relapsing Multiple Sclerosis (RIKNO 1.0)--Development of an
Outcome Instrument for Educational Interventions.
AB - BACKGROUND: Adequate risk knowledge of patients is a prerequisite for shared
decision making but few attempts have been made to develop assessment tools.
Multiple Sclerosis (MS) is a chronic inflammatory disease of young adults with an
increasing number of partially effective immunotherapies and therefore a
paradigmatic disease to study patient involvement. OBJECTIVE/METHODS: Based on an
item bank of MS risk knowledge items and patient feedback including perceived
relevance we developed a risk knowledge questionnaire for relapsing remitting
(RR) MS (RIKNO 1.0) which was a primary outcome measure in a patient education
trial (192 early RRMS patients). RESULTS: Fourteen of the RIKNO 1.0 multiple
choice items were selected based on patient perceived relevance and item
difficulty indices, and five on expert opinion. Mean item difficulty was 0.58,
ranging from 0.14 to 0.79. Mean RIKNO 1.0 score increased after the educational
intervention from 10.6 to 12.4 (p = 0.0003). Selected items were particularly
difficult (e.g. those on absolute risk reductions of having a second relapse) and
were answered correctly in only 30% of the patients, even after the intervention.
CONCLUSION: Despite its high difficulty, RIKNO 1.0 is a responsive instrument to
assess risk knowledge in RRMS patients participating in educational
interventions.
PMID- 26430888
TI - The Suramin Derivative NF449 Interacts with the 5-fold Vertex of the Enterovirus
A71 Capsid to Prevent Virus Attachment to PSGL-1 and Heparan Sulfate.
AB - NF449, a sulfated compound derived from the antiparasitic drug suramin, was
previously reported to inhibit infection by enterovirus A71 (EV-A71). In the
current work, we found that NF449 inhibits virus attachment to target cells, and
specifically blocks virus interaction with two identified receptors--the P
selectin ligand, PSGL-1, and heparan sulfate glycosaminoglycan--with no effect on
virus binding to a third receptor, the scavenger receptor SCARB2. We also
examined a number of commercially available suramin analogues, and newly
synthesized derivatives of NF449; among these, NF110 and NM16, like NF449,
inhibited virus attachment at submicromolar concentrations. PSGL-1 and heparan
sulfate, but not SCARB2, are both sulfated molecules, and their interaction with
EV-A71 is thought to involve positively charged capsid residues, including a
conserved lysine at VP1-244, near the icosahedral 5-fold vertex. We found that
mutation of VP1-244 resulted in resistance to NF449, suggesting that this residue
is involved in NF449 interaction with the virus capsid. Consistent with this
idea, NF449 and NF110 prevented virus interaction with monoclonal antibody MA28
7, which specifically recognizes an epitope overlapping VP1-244 at the 5-fold
vertex. Based on these observations we propose that NF449 and related compounds
compete with sulfated receptor molecules for a binding site at the 5-fold vertex
of the EV-A71 capsid.
PMID- 26430890
TI - Quantification of Pathologic Air Trapping in Lung Transplant Patients Using CT
Density Mapping: Comparison with Other CT Air Trapping Measures.
AB - To determine whether density mapping (DM) is more accurate for detection and
quantification of pathologic air trapping (pAT) in patients after lung
transplantation compared to other CT air trapping measures. One-hundred forty
seven lung and heart-lung transplant recipients underwent CT-examinations at
functional residual capacity (FRC) and total lung capacity (TLC) and PFT six
months after lung transplantation. Quantification of air trapping was performed
with the threshold-based method in expiration (EXP), density mapping (DM) and the
expiratory to inspiratory ratio of the mean lung density (E/I-ratio MLD). A non
rigid registration of inspiration-expiration CT-data with a following voxel-to
voxel mapping was carried out for DM. Systematic variation of attenuation ranges
was performed for EXP and DM and correlated with the ratio of residual volume to
total lung capacity (RV/TLC) by Spearman rank correlation test. AT was considered
pathologic if RV/TLC was above the 95th percentile of the predicted upper limit
of normal values. Receiver operating characteristic (ROC) analysis was performed.
The optimal attenuation range for the EXP method was from -790 HU to -950 HU
(EXP(-790 to -950HU)) (r = 0.524, p<0.001) to detect air trapping. Within the
segmented lung parenchyma, AT was best defined as voxel difference less than 80
HU between expiration and registered inspiration using the DM method. DM
correlated best with RV/TLC (r = 0.663, p<0.001). DM and E/I-ratio MLD showed a
larger AUC (0.78; 95% CI 0.69-0.86; 0.76, 95% CI 0.67-0.85) than EXP(-790 HU to
950 HU) (0.71, 95% CI 0.63-0.78). DM and E/I-ratio MLD showed better correlation
with RV/TLC and are more suited quantitative CT-methods to detect pAT in lung
transplant patients than the EXP(-790HU to -950HU).
PMID- 26430891
TI - Porcine SOX9 Gene Expression Is Influenced by an 18 bp Indel in the 5'
Untranslated Region.
AB - Sex determining region Y-box 9 (SOX9) is an important regulator of sex and
skeletal development and is expressed in a variety of embryonal and adult
tissues. Loss or gain of function resulting from mutations within the coding
region or chromosomal aberrations of the SOX9 locus lead to a plethora of
detrimental phenotypes in humans and animals. One of these phenotypes is the so
called male-to-female or female-to-male sex-reversal which has been observed in
several mammals including pig, dog, cat, goat, horse, and deer. In 38,XX sex
reversal French Large White pigs, a genome-wide association study suggested SOX9
as the causal gene, although no functional mutations were identified in affected
animals. However, besides others an 18 bp indel had been detected in the 5'
untranslated region of the SOX9 gene by comparing affected animals and controls.
We have identified the same indel (Delta18) between position +247 bp and +266 bp
downstream the transcription start site of the porcine SOX9 gene in four other
pig breeds; i.e., German Large White, Laiwu Black, Bamei, and Erhualian. These
animals have been genotyped in an attempt to identify candidate genes for porcine
inguinal and/or scrotal hernia. Because the 18 bp segment in the wild type 5'-UTR
harbours a highly conserved cAMP-response element (CRE) half-site, we analysed
its role in SOX9 expression in vitro. Competition and immunodepletion
electromobility shift assays demonstrate that the CRE half-site is specifically
recognized by CREB. Both binding of CREB to the wild type as well as the absence
of the CRE half-site in Delta18 reduced expression efficiency in HEK293T, PK-15,
and ATDC5 cells significantly. Transfection experiments of wild type and Delta18
SOX9 promoter luciferase constructs show a significant reduction of RNA and
protein levels depending on the presence or absence of the 18 bp segment. Hence,
the data presented here demonstrate that the 18 bp indel in the porcine SOX9 5'
UTR is of functional importance and may therefore indeed be a causative variation
in SOX9 associated traits.
PMID- 26430892
TI - Albuminuria as a Risk Factor for Anemia in Chronic Kidney Disease: Result from
the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease
(KNOW-CKD).
AB - BACKGROUND: Anemia is a common complication among patients with chronic kidney
disease (CKD), and it is associated with unfavorable clinical outcomes in
patients with CKD independent of the estimated glomerular filtration rate (eGFR).
We assessed the association of the urinary albumin-to-creatinine ratio (ACR) and
eGFR with anemia in CKD patients. METHODS: We conducted a cross-sectional study
using baseline data from the KoreaN Cohort Study for Outcome in Patients With
Chronic Kidney Disease (KNOW-CKD). Multiple regression analysis was performed to
identify the independent association of albuminuria with anemia. Furthermore,
odds ratios for anemia were calculated by cross-categorization of ACR and eGFR.
RESULTS: Among 1,456 patients, the mean age was 53.5 +/- 12.4 years, and the mean
eGFR and ACR were 51.9 +/- 30.5 mL/min per 1.73 m2 and 853.2 +/- 1,330.3 mg/g,
respectively. Anemia was present in 644 patients (40.5%). Multivariate analysis
showed that the odds ratio of anemia increased according to ACR levels, after
adjusting for age, sex, eGFR, body mass index, pulse pressure, cause of CKD, use
of erythropoiesis stimulating agents, serum calcium and ferritin (ACR < 30 mg/g
as a reference group; 30-299 mg/g, adjusted odds ratio (OR) = 1.43, 95%
confidence interval (CI) = 0.88-2.33; >=300 mg/g, adjusted OR = 1.86, 95% CI =
1.12-3.10). In addition, graded associations were observed in cross-categorized
groups of a higher ACR and eGFR compared to the reference group with an ACR <30
mg/g and eGFR >=60 mL/min per 1.73 m2. CONCLUSION: The present study demonstrated
that albuminuria was a significant risk factor for anemia in CKD patients
independent of the eGFR.
PMID- 26430893
TI - The Role of Self-Compassion in Buffering Symptoms of Depression in the General
Population.
AB - Self-compassion, typically operationalized as the total score of the Self
Compassion Scale (SCS; Neff, 2003b), has been shown to be related to increased
psychological well-being and lower depression in students of the social sciences,
users of psychology websites and psychotherapy patients. The current study builds
on the existing literature by examining the link between self-compassion and
depressive symptomatology in a sample representative of the German general
population (n = 2,404). The SCS subscales of self-judgment, isolation, and over
identification, and the "self-coldness", composite score, which encompass these
three negative subscales, consistently differed between subsamples of individuals
without any depressive symptoms, with any depressive syndromes, and with major
depressive disorder. The contribution of the positive SCS subscales of self
kindness, common humanity, and mindfulness to the variance in depressive
symptomatology was almost negligible. However, when combined to a "self
compassion composite", the positive SCS subscales significantly moderated the
relationship between "self-coldness" and depressive symptoms in the general
population. This speaks for self-compassion having the potential to buffer self
coldness related to depression--providing an argument for interventions that
foster self-caring, kind, and forgiving attitudes towards oneself.
PMID- 26430894
TI - Enhanced Immune Response to DNA Vaccine Encoding Bacillus anthracis PA-D4
Protects Mice against Anthrax Spore Challenge.
AB - Anthrax has long been considered the most probable bioweapon-induced disease. The
protective antigen (PA) of Bacillus anthracis plays a crucial role in the
pathogenesis of anthrax. In the current study, we evaluated the efficiency of a
genetic vaccination with the fourth domain (D4) of PA, which is responsible for
initial binding of the anthrax toxin to the cellular receptor. The eukaryotic
expression vector was designed with the immunoglobulin M (IgM) signal sequence
encoding for PA-D4, which contains codon-optimized genes. The expression and
secretion of recombinant protein was confirmed in vitro in 293T cells transfected
with plasmid and detected by western blotting, confocal microscopy, and enzyme
linked immunosorbent assay (ELISA). The results revealed that PA-D4 protein can
be efficiently expressed and secreted at high levels into the culture medium.
When plasmid DNA was given intramuscularly to mice, a significant PA-D4-specific
antibody response was induced. Importantly, high titers of antibodies were
maintained for nearly 1 year. Furthermore, incorporation of the SV40 enhancer in
the plasmid DNA resulted in approximately a 15-fold increase in serum antibody
levels in comparison with the plasmid without enhancer. The antibodies produced
were predominantly the immunoglobulin G2 (IgG2) type, indicating the predominance
of the Th1 response. In addition, splenocytes collected from immunized mice
produced PA-D4-specific interferon gamma (IFN-gamma). The biodistribution study
showed that plasmid DNA was detected in most organs and it rapidly cleared from
the injection site. Finally, DNA vaccination with electroporation induced a
significant increase in immunogenicity and successfully protected the mice
against anthrax spore challenge. Our approach to enhancing the immune response
contributes to the development of DNA vaccines against anthrax and other
biothreats.
PMID- 26430895
TI - Analysis of Food Pairing in Regional Cuisines of India.
AB - Any national cuisine is a sum total of its variety of regional cuisines, which
are the cultural and historical identifiers of their respective regions. India is
home to a number of regional cuisines that showcase its culinary diversity. Here,
we study recipes from eight different regional cuisines of India spanning various
geographies and climates. We investigate the phenomenon of food pairing which
examines compatibility of two ingredients in a recipe in terms of their shared
flavor compounds. Food pairing was enumerated at the level of cuisine, recipes as
well as ingredient pairs by quantifying flavor sharing between pairs of
ingredients. Our results indicate that each regional cuisine follows negative
food pairing pattern; more the extent of flavor sharing between two ingredients,
lesser their co-occurrence in that cuisine. We find that frequency of ingredient
usage is central in rendering the characteristic food pairing in each of these
cuisines. Spice and dairy emerged as the most significant ingredient classes
responsible for the biased pattern of food pairing. Interestingly while
individual spices contribute to negative food pairing, dairy products on the
other hand tend to deviate food pairing towards positive side. Our data
analytical study highlighting statistical properties of the regional cuisines,
brings out their culinary fingerprints that could be used to design algorithms
for generating novel recipes and recipe recommender systems. It forms a basis for
exploring possible causal connection between diet and health as well as
prospection of therapeutic molecules from food ingredients. Our study also
provides insights as to how big data can change the way we look at food.
PMID- 26430896
TI - Role and Variation of the Amount and Composition of Glomalin in Soil Properties
in Farmland and Adjacent Plantations with Reference to a Primary Forest in North
Eastern China.
AB - The glycoprotein known as glomalin-related soil protein (GRSP) is abundantly
produced on the hyphae and spores of arbuscular mycorrhizal fungi (AMF) in soil
and roots. Few studies have focused on its amount, composition and associations
with soil properties and possible land-use influences, although the data hints at
soil rehabilitation. By choosing a primary forest soil as a non-degraded
reference, it is possible to explore whether afforestation can improve degraded
farmland soil by altering GRSP. In this paper, close correlations were found
between various soil properties (soil organic carbon, nitrogen, pH, electrical
conductivity (EC), and bulk density) and the GRSP amount, between various soil
properties and GRSP composition (main functional groups, fluorescent substances,
and elements). Afforestation on farmland decreased the EC and bulk density (p <
0.05). The primary forest had a 2.35-2.56-fold higher GRSP amount than those in
the plantation forest and farmland, and GRSP composition (tryptophan-like and
fulvic acid-like fluorescence; functional groups of C-H, C-O, and O-H; elements
of Al, O, Si, C, Ca, and N) in primary forest differed from those in plantation
forest and farmland (p < 0.05). However, no evident differences in GRSP amount
and composition were observed between the farmland and the plantation forest. Our
finding highlights that 30 years poplar afforestation on degraded farmland is not
enough to change GRSP-related properties. A longer period of afforestation with
close-to-nature managements may favor the AMF-related underground recovery
processes.
PMID- 26430898
TI - XXV Annual Meeting of the Latin American Pediatric Endocrinology Society (SLEP),
Puerto Varas, Chile, November 3-6, 2015: Abstract.
PMID- 26430897
TI - Family-Based Association Study of Pulmonary Function in a Population in Northeast
Asia.
AB - The spirometric measurement of pulmonary function by measuring the forced
expiratory volume in one second (FEV1) is a heritable trait that reflects the
physiological condition of the lung and airways. Genome-wide linkage and
association studies have identified a number of genes and genetic loci associated
with pulmonary function. However, limited numbers of studies have been reported
for Asian populations. In this study, we aimed to investigate genetic evidence of
pulmonary function in a population in northeast Asia. We conducted a family-based
association test with 706 GENDISCAN study participants from 72 Mongolian families
to determine candidate genetic determinants of pulmonary function. For the
replication, we chose seven candidate single nucleotide polymorphisms (SNPs) from
the 5 loci, and tested 1062 SNPs for association with FEV1 from 2,729 subjects of
the Korea Healthy Twin study. We identified TMEM132C as a potential candidate
gene at 12q24.3, which is a previously reported locus of asthma and spirometric
indices. We also found two adjacent candidate genes (UNC93A and TTLL2) in the
6q27 region, which has been previously identified as a pulmonary function locus
in the Framingham cohort study. Our findings suggest that novel candidate genes
(TMEM132C, UNC93A and TTLL2) in two different regions are associated with
pulmonary function in a population in northeast Asia.
PMID- 26430900
TI - 47,XY,+der(X)t(X;18)(p11.4;p11.22): A Unique Aneuploidy Associated with
Klinefelter Syndrome due to an Extra Derivative X Chromosome Inherited
Maternally.
AB - A derivative X chromosome formed by translocation involving an X chromosome and a
chromosome 18 in a Klinefelter syndrome (KS) patient with a 47,XXY karyotype has
not been reported before. In this study, we present the clinical and molecular
cytogenetic characteristics. The patient presented with small testes and
azoospermia. G-banding analysis identified the karyotype as 47,XY,del(X)(p?11.4).
Array CGH detected a 10.36-Mb duplication of chromosome region 18p11.22p11.32
(14,316-10,377,516) and a 111.18-Mb duplication of chromosome region Xp11.4q28
(61,931, 689-155,111,583), in addition to the normal chromosome 18 and an X
chromosome. FISH results further revealed the extra 18p located at the end of the
short arm of a deleted X chromosome, forming a derivative X chromosome. Finally,
we identified the karyotype of the patient as 47,XY,+der(X)t(X;18)(p11.4;p11.22).
The derivative X chromosome was maternally inherited. To our knowledge, this rare
karyotype has not yet been reported in the literature. The present study may
suggest a novel karyotype associated with KS.
PMID- 26430899
TI - Precursor-Directed Combinatorial Biosynthesis of Cinnamoyl, Dihydrocinnamoyl, and
Benzoyl Anthranilates in Saccharomyces cerevisiae.
AB - Biological synthesis of pharmaceuticals and biochemicals offers an
environmentally friendly alternative to conventional chemical synthesis. These
alternative methods require the design of metabolic pathways and the
identification of enzymes exhibiting adequate activities. Cinnamoyl,
dihydrocinnamoyl, and benzoyl anthranilates are natural metabolites which possess
beneficial activities for human health, and the search is expanding for novel
derivatives that might have enhanced biological activity. For example,
biosynthesis in Dianthus caryophyllus is catalyzed by hydroxycinnamoyl/benzoyl
CoA:anthranilate N-hydroxycinnamoyl/ benzoyltransferase (HCBT), which couples
hydroxycinnamoyl-CoAs and benzoyl-CoAs to anthranilate. We recently demonstrated
the potential of using yeast (Saccharomyces cerevisiae) for the biological
production of a few cinnamoyl anthranilates by heterologous co-expression of 4
coumaroyl:CoA ligase from Arabidopsis thaliana (4CL5) and HCBT. Here we report
that, by exploiting the substrate flexibility of both 4CL5 and HCBT, we achieved
rapid biosynthesis of more than 160 cinnamoyl, dihydrocinnamoyl, and benzoyl
anthranilates in yeast upon feeding with both natural and non-natural cinnamates,
dihydrocinnamates, benzoates, and anthranilates. Our results demonstrate the use
of enzyme promiscuity in biological synthesis to achieve high chemical diversity
within a defined class of molecules. This work also points to the potential for
the combinatorial biosynthesis of diverse and valuable cinnamoylated,
dihydrocinnamoylated, and benzoylated products by using the versatile biological
enzyme 4CL5 along with characterized cinnamoyl-CoA- and benzoyl-CoA-utilizing
transferases.
PMID- 26430901
TI - Calcitonin Gene-Related Peptide Improves Hypoxia-Induced Inflammation and
Apoptosis via Nitric Oxide in H9c2 Cardiomyoblast Cells.
AB - OBJECTIVES: The aim of this work was to investigate whether calcitonin gene
related peptide (CGRP) plays a protective role in cardiomyocytes against hypoxia
induced inflammation and apoptosis via an NO-mediated pathway. METHODS: H9c2
cardiac cells were exposed to hypoxia for 2 h to establish a model of myocardial
hypoxic-ischemic injury. The cells were pretreated with either CGRP or nitric
oxide synthase (NOS) inhibitor (L-NAME) before being exposed to hypoxia for 30
min. Cell viability was analyzed using a cell counter kit 8 (CCK-8). The levels
of IL-6 and TNF-alpha were determined by the corresponding enzyme-linked
immunosorbent assay. The expression levels of several apoptosis proteins (p53,
caspase-3, cytochrome C) and NOS were detected by Western blot assays. An NO kit
was used to evaluate the production of NO. RESULTS: Pretreatment of H9c2 cardiac
cells with CGRP for 30 min prior to exposure to hypoxia markedly improved cell
viability (83.57 +/- 3.21 vs. 62.83 +/- 8.30%, p < 0.001); the same effect was
observed following pretreatment with the NOS inhibitor L-NAME (89.34 +/- 5.95 vs.
75.01 +/- 5.61%, p < 0.01). Pretreatment with CGRP also significantly attenuated
the inflammatory responses induced by hypoxia, as evidenced by decreases of the
levels of both IL-6 (193.21 +/- 13.54 vs. 293.38 +/- 56.49%, p < 0.001) and TNF
alpha (207.71 +/- 44.27 vs. 281.46 +/- 64.88%, p < 0.001). Additionally, CGRP
significantly decreased the hypoxia-induced overexpression of the apoptotic
proteins (p53: 0.27 +/- 0.10 vs. 0.87 +/- 0.30, p < 0.001; caspase-3: 0.65 +/-
0.15 vs. 0.98 +/- 0.26, p < 0.001; cytochrome C: 1.51 +/- 0.39 vs. 2.80 +/- 0.69,
p < 0.001) and enhanced the expression of both endothelial NOS (eNOS; 0.59 +/-
0.24 vs. 0.37 +/- 0.14, p < 0.05) and phosphorylated eNOS (0.60 +/- 0.13 vs. 0.40
+/- 0.07, p < 0.05). Furthermore, the application of both L-NAME and CGRP
attenuated the hypoxia-induced expression of inducible NOS (iNOS; p < 0.05) and
enhanced a hypoxia-mediated decrease in NO (p < 0.01). Interestingly, the
expression levels of cell apoptosis (p < 0.05), iNOS and eNOS (p < 0.05) were
decreased with L-NAME and CGRP cotreatment following 2 h of acute hypoxia, but
the apoptotic factors (p < 0.05) were increased compared with only CGRP
pretreatment. CONCLUSION: CGRP protects cardiomyocytes from hypoxia-induced
inflammation and apoptosis by modulating NO production.
PMID- 26430902
TI - Coupled Human-Environment Dynamics of Forest Pest Spread and Control in a Multi
Patch, Stochastic Setting.
AB - BACKGROUND: The transportation of camp firewood infested by non-native forest
pests such as Asian long-horned beetle (ALB) and emerald ash borer (EAB) has
severe impacts on North American forests. Once invasive forest pests are
established, it can be difficult to eradicate them. Hence, preventing the long
distance transport of firewood by individuals is crucial. METHODS: Here we
develop a stochastic simulation model that captures the interaction between
forest pest infestations and human decisions regarding firewood transportation.
The population of trees is distributed across 10 patches (parks) comprising a
"low volume" partition of 5 patches that experience a low volume of park
visitors, and a "high volume" partition of 5 patches experiencing a high visitor
volume. The infestation spreads within a patch--and also between patches-
according to the probability of between-patch firewood transportation.
Individuals decide to transport firewood or buy it locally based on the costs of
locally purchased versus transported firewood, social norms, social learning, and
level of concern for observed infestations. RESULTS: We find that the average
time until a patch becomes infested depends nonlinearly on many model parameters.
In particular, modest increases in the tree removal rate, modest increases in
public concern for infestation, and modest decreases in the cost of locally
purchased firewood, relative to baseline (current) values, cause very large
increases in the average time until a patch becomes infested due to firewood
transport from other patches, thereby better preventing long-distance spread.
Patches that experience lower visitor volumes benefit more from firewood movement
restrictions than patches that experience higher visitor volumes. Also, cross
patch infestations not only seed new infestations, they can also worsen existing
infestations to a surprising extent: long-term infestations are more intense in
the high volume patches than the low volume patches, even when infestation is
already endemic everywhere. CONCLUSIONS: The success of efforts to prevent long
distance spread of forest pests may depend sensitively on the interaction between
outbreak dynamics and human social processes, with similar levels of effort
producing very different outcomes depending on where the coupled human and
natural system exists in parameter space. Further development of such modeling
approaches through better empirical validation should yield more precise
recommendations for ways to optimally prevent the long-distance spread of
invasive forest pests.
PMID- 26430903
TI - Structure of Bolaamphiphile Sophorolipid Micelles Characterized with SAXS, SANS,
and MD Simulations.
AB - The micellar structure of sophorolipids, a glycolipid bolaamphiphile, is analyzed
using a combination of small-angle X-ray scattering (SAXS), small-angle neutron
scattering (SANS), and molecular dynamics (MD) simulations. Numerical modeling of
SAXS curves shows that micellar morphology in the noncharged system (pH< 5) is
made of prolate ellipsoids of revolution with core-shell morphology. Opposed to
most surfactant systems, the hydrophilic shell has a nonhomogeneous distribution
of matter: the shell thickness in the axial direction of the ellipsoid is found
to be practically zero, while it measures about 12 A at its cross-section, thus
forming a "coffee bean"-like shape. The use of a contrast-matching SANS
experiment shows that the hydrophobic component of sophorolipids is actually
distributed in a narrow spheroidal region in the micellar core. These data seem
to indicate a complex distribution of sophorolipids within the micelle, divided
into at least three domains: a pure hydrophobic core, a hydrophilic shell, and a
region of less defined composition in the axial direction of the ellipsoid. To
account for these results, we make the hypothesis that sophorolipid molecules
acquire various configurations within the micelle including bent and linear,
crossing the micellar core. These results are confirmed by MD simulations which
do show the presence of multiple sophorolipid configurations when passing from
spherical to ellipsoidal aggregates. Finally, we also used Rb(+) and Sr(2+)
counterions in combination with anomalous SAXS experiments to probe the
distribution of the COO(-) group of sophorolipids upon small pH increase (5 < pH
< 7), where repulsive intermicellar interactions become important. The poor ASAXS
signal shows that the COO(-) groups are rather diffused in the broad hydrophilic
shell rather than at the outer micellar/water interface.
PMID- 26430904
TI - Review of Bioptic Gleason Scores by Central Pathologist Modifies the Risk
Classification in Prostate Cancer.
AB - OBJECTIVES: The Gleason score (GS) is the primary classification of clinical risk
in prostate cancer (PCa). Here, we estimated the factors predictive of accordance
of local and central pathologist-dependent GS and clinical risk classification in
an increased number of cases. METHODS: Between January 2009 and December 2013,
388 patients were diagnosed with PCa by 80 independent pathologists from local
communities and were referred to our hospital. Validation of the GS with needle
core biopsy specimens was carried out by a single central pathologist, and
clinical risk, according to the D'Amico risk classification, was determined.
Discrepancies between the GS and risk classification, based on the GS estimated
by the local or central pathologist, were reviewed, and predictive factors for
accordance of clinical risk classification were estimated. RESULTS: When
pathological results were compared, 59.5% of cases were given concordant GSs by
local and central pathologists. A significant discrepancy existed in the
classification of intermediate risk (p < 0.0001). Multivariate analysis indicated
that local pathologist-dependent GS7, lower prostate-specific antigen (<= 10
ng/ml), and lower T stage (T1 or T2a) were significant predictive factors for
discordance with the central pathologist-dependent risk classification.
CONCLUSION: Review of bioptic GSs by central pathologists affected discrepancies
in risk classification in patients with PCa.
PMID- 26430906
TI - The spontaneous formation and plasmonic properties of ultrathin gold-silver
nanorods and nanowires stabilized in oleic acid.
AB - Ultrathin Au-Ag alloy nanorods and nanowires of different lengths and ca. 1.9 nm
diameter are prepared through a low-temperature decomposition of the precursor
[Au2Ag2(C6F5)4(OEt2)2]n in oleic acid. This nanostructure formation has been
studied through TEM, HRTEM, EDS, HS-SPME-GC-MS and (19)F NMR spectroscopy. The
UNRs and UNWs display a length-dependent broad band in the mid-IR region that is
related to the longitudinal mode of the surface plasmon resonance of the
ultrathin nanostructures.
PMID- 26430905
TI - Pain in older adults: development of a tool for measuring knowledge of
residential aged care staff.
AB - OBJECTIVE: To develop a psychometrically sound tool for measuring the knowledge
of nursing and care staff about the experience, assessment and management of pain
in older people (including people with dementia) for use in the residential aged
care setting. METHODS: The Pain in Older Adults Knowledge Survey (POAKS) was
developed and tested in two phases. Phase 1 involved developing an initial item
pool with good content validity based on a review of the research literature and
a modified Delphi technique involving national and international experts. A pool
of 24 items was developed for testing. Initial testing of the psychometric
properties of the POAKS with 30 university employees led to refinement and final
wording of items. Phase 2 involved testing of the psychometric properties of the
POAKS with 279 respondents, including first year (n = 176) and third year (n =
70) nursing students and staff in a residential aged care service (n = 33).
RESULTS: Results established the content validity and internal consistency of the
POAKS and supported its use as an instrument to measure nursing staff knowledge
about the experience, assessment and management of pain in older people.
CONCLUSIONS: The POAKS will enable residential aged care facilities to measure
the level of knowledge among nursing and care staff about pain in older people
(including people with dementia). The measure provides a basis for the
development and implementation of educational interventions to address knowledge
gaps that may impact on the quality of care provided.
PMID- 26430907
TI - Comparison of conventional versus three-dimensional ultrasound in fetal renal
pelvis measurement and their potential prediction of neonatal uropathies.
AB - OBJECTIVE: To establish a threshold value for fetal renal pelvis dilatation
measured by automatic volume calculation (SonoAVC) in the third trimester of
pregnancy to predict neonatal uropathies, and to compare these results with
conventional antero-posterior (AP) measurement, fetal kidney 3D volume and renal
parenchymal thickness. METHODS: In a prospective cohort study, 125 fetuses with
renal pelvis AP diameter of >=5 mm both at 20 weeks of gestation and in the third
trimester, underwent an additional 3D volume measurement of the fetal kidney in
the third trimester. Receiver operating characteristic (ROC) curves for
establishing threshold values for fetal renal pelvis volume, AP measurement,
fetal kidney volume and renal parenchymal thickness to predict neonatal
uropathies were analyzed. Also, sensitivity, specificity, area under the curve
(AUC) and likelihood ratios were calculated. RESULTS: A cut-off point of 1.58 cm3
was identified in the third trimester of pregnancy (AUC 0.865 (95% CI 0.789
0.940), sensitivity 76.3%, specificity 87.4%, LR+ 6.06, LR- 0.27) for
measurements with SonoAVC. A cut-off value of 11.5 mm was established in the
third trimester of pregnancy (AUC 0.828 (95% CI 0.737-0.918), sensitivity 71.1%,
specificity 85.1%, LR+ 4.77, LR- 0.34) for the conventional AP measurement. A cut
off point for fetal kidney volume was calculated at 13.29 cm3 (AUC 0.769 (95% CI
0.657-0.881), sensitivity 71%, specificity 66%, LR+ 2.09, LR- 0.44). For renal
parenchymal thickness, a cut-off point of 8.4 mm was established (AUC 0.216 (95%
CI 0.117-0.315), sensitivity 31.6%, specificity 32.6%, LR+ 0.47, LR- 2.10).
CONCLUSION: This study demonstrates that 3D fetal renal pelvis volume
measurements and AP measurements both have a good and comparable diagnostic
performance, fetal renal volume a fair accuracy and renal parenchymal thickness a
poor accuracy in predicting postnatal renal outcome.
PMID- 26430908
TI - Charge screening in RNA: an integral route for dynamical enhancements.
AB - Electrostatic interactions of RNA are at the center of determining the dynamical
flexibility and structural stability. By analysing neutron scattering
spectroscopy, we show that fast dynamics of hydrated tRNA on ps to ns timescales
increases with stronger charge screening, while its structural stability either
increases or remains largely unchanged. An unprecedented electrostatic threshold
for the onset of additional flexibility is induced from the correlation between
the charge-screening density of counterions and the promoted dynamical
properties. The results demonstrate that the enhanced dynamical flexibility of
tRNA originates from local conformational relaxation coupled with stabilized
charge screening rather than governed by fluctuation of hydrated counterions. The
present study casts light on the specificity of electrostatic interactions in the
thermodynamic balance between the dynamical flexibility and structural stability
of RNA.
PMID- 26430910
TI - Imatinib discontinuation for hypereosinophilic syndrome harboring the FIP1L1
PDGFRA transcript.
PMID- 26430909
TI - FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage
Independently of FANCD2.
AB - The Fanconi anemia (FA)-BRCA pathway mediates repair of DNA interstrand
crosslinks. The FA core complex, a multi-subunit ubiquitin ligase, participates
in the detection of DNA lesions and monoubiquitinates two downstream FA proteins,
FANCD2 and FANCI (or the ID complex). However, the regulation of the FA core
complex itself is poorly understood. Here we show that the FA core complex
proteins are recruited to sites of DNA damage and form nuclear foci in S and G2
phases of the cell cycle. ATR kinase activity, an intact FA core complex and
FANCM-FAAP24 were crucial for this recruitment. Surprisingly, FANCI, but not its
partner FANCD2, was needed for efficient FA core complex foci formation.
Monoubiquitination or ATR-dependent phosphorylation of FANCI were not required
for the FA core complex recruitment, but FANCI deubiquitination by USP1 was.
Additionally, BRCA1 was required for efficient FA core complex foci formation.
These findings indicate that FANCI functions upstream of FA core complex
recruitment independently of FANCD2, and alter the current view of the FA-BRCA
pathway.
PMID- 26430911
TI - Microbes, Mineral Evolution, and the Rise of Microcontinents-Origin and
Coevolution of Life with Early Earth.
AB - Earth is the most mineralogically diverse planet in our solar system, the direct
consequence of a coevolving geosphere and biosphere. We consider the possibility
that a microbial biosphere originated and thrived in the early Hadean-Archean
Earth subseafloor environment, with fundamental consequences for the complex
evolution and habitability of our planet. In this hypothesis paper, we explore
possible venues for the origin of life and the direct consequences of microbially
mediated, low-temperature hydrothermal alteration of the early oceanic
lithosphere. We hypothesize that subsurface fluid-rock-microbe interactions
resulted in more efficient hydration of the early oceanic crust, which in turn
promoted bulk melting to produce the first evolved fragments of felsic crust.
These evolved magmas most likely included sialic or tonalitic sheets, felsic
volcaniclastics, and minor rhyolitic intrusions emplaced in an Iceland-type
extensional setting as the earliest microcontinents. With the further development
of proto-tectonic processes, these buoyant felsic crustal fragments formed the
nucleus of intra-oceanic tonalite-trondhjemite-granitoid (TTG) island arcs. Thus
microbes, by facilitating extensive hydrothermal alteration of the earliest
oceanic crust through bioalteration, promoted mineral diversification and may
have been early architects of surface environments and microcontinents on young
Earth. We explore how the possible onset of subseafloor fluid-rock-microbe
interactions on early Earth accelerated metavolcanic clay mineral formation,
crustal melting, and subsequent metamorphic mineral evolution. We also consider
environmental factors supporting this earliest step in geosphere-biosphere
coevolution and the implications for habitability and mineral evolution on other
rocky planets, such as Mars.
PMID- 26430913
TI - Lipid-based nanocarriers for breast cancer treatment - comprehensive review.
AB - Breast cancer is the second leading cancer-related disease as the most common non
cutaneous malignancy among women. Curative options for breast cancer are limited,
therapeutically substantial and associated with toxicities. Emerging
nanotechnologies exhibited the possibility to treat or target breast cancer.
Among the nanoparticles, various lipid nanoparticles namely, liposomes, solid
lipid nanoparticles, nanostructured lipid carriers and lipid polymer hybrid
nanoparticles have been developed over the years for the breast cancer therapy
and evidences are documented. Concepts are confined in lab scale, which needs to
be transferred to large scale to develop active targeting nanomedicine for the
clinical utility. So, the present review highlights the recently published
studies in the development of lipid-based nanocarriers for breast cancer
treatment.
PMID- 26430912
TI - The Role of the Y Box Binding Protein 1 C-Terminal Domain in Vascular Endothelial
Cell Proliferation, Apoptosis, and Angiogenesis.
AB - Different domains of the multifunctional transcription factor Y-box binding
protein 1 (YB1) regulate proliferation, differentiation, and apoptosis by
transactivating or repressing the promoters of various genes. Here we report that
the C-terminal domain of YB1 (YB1 CTD) is involved in endothelial cell
proliferation, apoptosis, and tube formation. The oligo pull-down assays
demonstrated that YB1 directly binds double-stranded GC box sequences in
endothelial cells through the 125-220 amino acids. Adenovirus expression vectors
harboring green fluorescent protein (GFP) or GFP-tagged YB1 CTD were constructed
and used to infect EA.hy926 endothelial cells. Overexpression of the YB1 CTD
significantly increased p21 expression, decreased cyclin B1 expression, and
inhibited the proliferation of EA.hy926 cells. YB1 CTD overexpression also
increased Bax and active caspase 3 expression, decreased Bcl-2 expression, and
induced apoptosis in EA.hy926 cells. Furthermore, overexpression of the YB1 CTD
significantly suppressed migration and tube formation in EA.hy926 cells. Finally,
YB1 CTD decreased ERK1/2 phosphorylation in EA.hy926 cells. These findings
demonstrated vital roles for YB1 in endothelial cell proliferation, apoptosis,
and tube formation through transcriptional regulation of GC box-related genes.
PMID- 26430919
TI - Constructing a three-dimensional electrical model of a living cochlear implant
user's cochlea.
AB - BACKGROUND: Hearing performance varies greatly among users of cochlear implants.
Current three-dimensional cochlear models that predict the electrical fields
inside a stimulated cochlea and their effect on neural excitation are generally
based on a generic human or guinea pig cochlear shape that does not take inter
user morphological variations into account. This precludes prediction of user
specific performance. AIMS: The aim of this study is to develop a model of the
implanted cochlea of a specific living human individual and to assess if the
inclusion of morphological variations in cochlear models affects predicted
outcomes significantly. METHODS: Five three-dimensional electric volume
conduction models of the implanted cochleae of individual living users were
constructed from standard CT scan data. These models were embedded in head models
that include monopolar return electrodes in accurate anatomic positions.
Potential distributions and neural excitation patterns were predicted for each of
the models. RESULTS: Modeled potential distributions and neural excitation
profiles (threshold amplitudes, center frequencies, and bandwidths) are affected
by user-specific cochlear morphology and electrode placement within the cochlea.
CONCLUSIONS: This work suggests that the use of user-specific models is indicated
when more detailed analysis is required than what is available from generic
models. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26430918
TI - Generation of a MDCK cell line with constitutive expression of the
Enteropathogenic E. coli effector protein Map as an in vitro model of
pathogenesis.
AB - Enteropathogenic E. coli (EPEC) cause diarrhea and are the major cause of
mortality in developing countries. EPEC use a type III secretion system to
deliver effector proteins into the host epithelial cells. To understand the
functions of these effectors, majority of studies on EPEC pathogenesis have
relied on infections of animals or cell lines with wild type strains of EPEC or
mutant strains deficient in one or more effectors. While these studies have
provided valuable data, it can be difficult to assess functions of an individual
effector in the presence of other EPEC effectors. Recent studies have reported
the use of transient transfections with plasmids encoding various EPEC effectors
into different cell lines. However, variable transfection efficiencies and
expression levels of the effector proteins coupled with their expression for
relatively short periods of time pose a problem if the long term effects of these
effectors need to be examined. We have generated a MDCK cell line with
constitutive expression of the EPEC effector Map (Mitochondrial associated
protein) for efficient stable expression of EGFP-tagged Map. We observed that the
constitutive expression of Map increased the permeability of charged and non
charged molecules. We also generated polyclonal antibodies against Map and
checked for their specificity in MDCK-Map expressing cells. Map has been reported
to contribute to the onset of diarrhea but the underlying mechanism is yet to be
identified. The MDCK-Map cell line and the anti-Map antibodies generated by us
can be used for in vitro studies to examine the role of Map in EPEC pathogenesis.
PMID- 26430920
TI - Derivation of a Cross-Domain Embedded Performance Validity Measure in Traumatic
Brain Injury.
AB - OBJECTIVE: Performance validity assessment is increasingly considered standard
practice in neuropsychological evaluations. The current study extended research
on logistically derived performance validity tests (PVTs) by utilizing
neuropsychological measures from multiple cognitive domains instead of from a
single measure or a single cognitive domain. METHOD: A logistic-derived PVT was
calculated using several measures from multiple cognitive domains, including
verbal memory (California Verbal Learning Test-II Trial 5, Total Hits, and False
Positives), attention (Brief Test of Attention Total score), and language (Boston
Naming Test T-score, and Animal Fluency T-score). Due to its cross-domain nature,
the cross-domain logistic-derived embedded PVT was hypothesized to have excellent
classification accuracy for non-credible performance. Participants included 224
patients who completed all measures and were moderate to severe traumatic brain
injury (STBI) patients (N = 66), possible mild TBI (MTBI-FAIL) patients who
failed at least 2 independent PVTs (N = 67), and possible mild TBI patients who
passed all PVTs (MTBI-PASS; N = 91). Logistic regression and ROC analyses were
conducted on the MTBI-FAIL group and the STBI group. RESULTS: Multivariate
analysis of variance indicated that the MTBI-FAIL group was significantly lower
on all measures than the MTBI-PASS and the STBI groups. Using logistic
regression, CVLT Total Hits, BTA, and the CVLT False Positives best
differentiated between the MTBI-FAIL and STBI groups. The logistically derived
PVT had excellent classification accuracy (area under the curve [AUC] = .84),
with sensitivity at .54 when specificity was set at .90, higher than any
individual variable. CONCLUSIONS: Findings support the use of this logistical
derived variable as an embedded PVT and support further research with this type
of methodology.
PMID- 26430922
TI - Validity of self-reported sedentary time differs between Australian rural men
engaged in office and farming occupations.
AB - Rural Australians have a higher likelihood of chronic disease than urban
Australians, particularly male farmers. Chronic disease has been associated with
occupational sedentary time. The aim was to validate the self-report of sedentary
time in men in contrasting rural occupations. Farmers (n = 29) and office workers
(n = 28), age 30-65 years, were recruited from the Riverland region of South
Australia. Daily sedentary time and number of breaks in sedentary time were self
reported and measured objectively using body-worn inclinometers. Correlational
analyses were conducted between self-reported and objectively measured variables,
separately by occupation. There was a significant correlation between self
reported and objectively measured sedentary time in the whole sample (r = 0.44, P
= 0.001). The correlation among office workers was significant (r = 0.57, P =
0.003) but not among farmers (r = 0.08, P = 0.68). There were no significant
correlations between self-reported and measured number of breaks in sedentary
time, for the whole sample (rho = -0.03, P = 0.83), office workers (rho = 0.17, P
= 0.39) and farmers (rho = -0.22, P = 0.25). In conclusion, the validity of self
report of sedentary behaviours by farmers was poor. Further research is needed to
develop better performing self-report instruments or more accessible objective
measures of sedentary behaviour in this population.
PMID- 26430923
TI - The Effect of Systemic Tamsulosin Hydrochloride on Choroidal Thickness Measured
by Enhanced Depth Imaging Spectral Domain Optical Coherence Tomography.
PMID- 26430921
TI - Pneumococcal nasopharyngeal carriage in children <5 years of age visiting the
pediatric emergency room in relation to PCV7 and PCV13 introduction in southern
Israel.
AB - The 7-valent and the 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13,
respectively) were introduced to the Israeli National Immunization plan in July
2009 and November 2010, respectively. Our aim was to assess pneumococcal
conjugate vaccines (PCVs) uptake and dynamics in serotype-specific pneumococcal
nasopharyngeal (NP) carriage in children <5 years old in southern Israel, during
the immediate 5 y following PCV introduction. This was an ongoing, prospective,
population-based, active surveillance, from July 2009 through December 2014. PCVs
uptake and NP cultures were obtained daily from children seen at the Pediatric
Emergency Room for any reason. Overall, 10,702 vaccine status and 7,610 NP swabs
were obtained. Both PCV7 and PCV13 uptake were high, reaching ~90% by July 2012
and December 2013, respectively. All-pneumococcal carriage rates significantly
declined by 10%, from 54.3% in the early-PCV7 period, to 49.1% in the PCV13
impact period. The respective declines for PCV7, 6A and additional PCV13
serotypes carriage rates were 76%, 90% and 66%. In contrast, non-PCV13 serotypes
carriage rates increased significantly throughout the study by 71%. All
pneumococcal carriage rates in children <12 months old decreased significantly
by 15%, with similar trends observed in other age groups. Initially, all
pneumococcal carriage rates were 45.7%, and 61.9% in Jewish and Bedouin children,
respectively (P < 0.001), with a significant 17% reduction throughout the study
observed only in Bedouins. While early carriage rates were higher in unvaccinated
children compared to vaccinated children, PCV impact on carriage were similar in
both groups. In conclusion, a relatively moderate decline in pneumococcal
carriage rates, facilitated by a substantial decrease of vaccine-serotypes and
increase of non-vaccine serotypes was observed in the immediate period following
PCVs introduction in southern Israel.
PMID- 26430924
TI - Downregulation of Proteinase-Activated Receptor-2, Interleukin-17, and Other
Proinflammatory Genes by Subantimicrobial Doxycycline Dose in a Rat Periodontitis
Model.
AB - BACKGROUND: Subantimicrobial dose doxycycline (SDD) has been used as an adjunct
in periodontal treatment because of its matrix metalloproteinase inhibition
properties. Although the benefits of SDD therapy, such as improvement in the
parameters of periodontal probing depth and clinical attachment level, have been
proven in multiple clinical studies, the comprehension of other biologic
mechanisms of action on periodontitis remains poorly investigated. Therefore,
this animal-model study evaluated the effects of SDD monotherapy on the
expressions of the following key proinflammatory genes: proteinase-activated
receptor-2 (PAR2), tumor necrosis factor (TNF)-alpha, interleukin (IL)-17, and IL
1beta. METHODS: Male Wistar rats were assigned randomly to the following: 1)
control group: no ligature-induced periodontitis and no treatment; 2) ligature
group: ligature-induced periodontitis and placebo treatment; and 3) ligature +
doxycycline group: ligature-induced periodontitis and SDD treatment. After the
experimental time, animals were sacrificed, and reverse transcription-polymerase
chain reaction was performed to analyze the mRNA expression of IL-1beta, IL-17,
TNF-alpha, and PAR2 in gingival tissue samples. Histologic analyses were
performed on the furcation region and mesial gingiva of mandibular first molars
to measure periodontal bone loss and collagen content. RESULTS: SDD
administration significantly downregulated PAR2, IL-17, TNF-alpha, and IL-1beta
mRNA expressions (P <0.05). In addition, SDD treatment was accompanied by lower
rates of alveolar bone loss (P <0.05) and maintenance of the amount of gingival
collagen fibers. CONCLUSION: These findings reveal new perspectives regarding SDD
efficacy because it can be partially related to proinflammatory gene expression
modulation, even considering PAR2 and IL-17, which has not been investigated thus
far.
PMID- 26430925
TI - Analyses of Gingival Adhesion Molecules in Periodontitis: Theoretical In Silico,
Comparative In Vivo, and Explanatory In Vitro Models.
AB - BACKGROUND: A deeper understanding of periodontitis pathophysiology is central to
future development of novel biomarkers and therapeutics. The following is
reported here: 1) an in silico network model of interactions among cell adhesion
molecules and a network-focused microarray analysis of the corresponding genes in
periodontitis; 2) analysis of secretions of adhesion molecules in gingival tissue
samples from patients with periodontitis and healthy controls; and 3) effect of
the human neutrophilic peptide-1 (HNP-1) on epithelial adhesion molecules.
METHODS: The network model identified 85 nodes in relation to the interactions of
adhesion molecules. Subsequently, the relative gene expression was overlaid on
the network model. Differential gene expression was analyzed, and false discovery
rate control was performed for statistical assessment of the microarray data.
Both tissue and cell culture samples were immunostained for desmocollin (DSC)2,
occludin (OCLN), desmoglein (DSG)1, tight junction protein 2, and gap junction
protein alpha. RESULTS: The differential gene expression analysis revealed that
the epithelial adhesion molecules were significantly lower in abundance in
individuals with periodontitis than controls. In contrast, the genes for
leukocyte adhesion molecules showed a significant upregulation. Immunostainings
revealed elevated secretions of both DSG1 and OCLN in periodontitis. An in vitro
model suggested reduced DSC2 and OCLN secretions in the presence of HNP-1.
CONCLUSIONS: Gene expression of gingival adhesion molecules in periodontitis is
regulated by leukocyte transmigration, whereas the neutrophilic antimicrobial
peptide HNP-1 is noted as a putative regulator of epithelial adhesion molecules.
These observations contribute to the key mechanisms by which future biomarkers
might be developed for periodontitis.
PMID- 26430926
TI - Pilot Study on Oral Health Status as Assessed by an Active Matrix
Metalloproteinase-8 Chairside Mouthrinse Test in Adolescents.
AB - BACKGROUND: Matrix metalloproteinase (MMP)-8 is a major destructive collagenase
involved in periodontitis and can be regarded as a periodontitis biomarker. A
neutrophil collagenase 2 (active MMP-8 [aMMP-8]) oral fluid immunoassay has
recently been demonstrated to be a periodontitis risk indicator among adults. The
aim of this study is to investigate whether a point-of-care mouthrinse test based
on an aMMP-8 immunoassay could identify patients with oral inflammatory burden
(periodontitis and caries) among adolescents with early pathologic findings.
METHODS: This cross-sectional study was carried out at the Kotka Health Center,
Finland. First, the aMMP-8 chairside mouthrinse test was performed on enrolled
individuals (adolescents aged 15 to 17 years, n = 47), and the results were read
based on a color change within 5 minutes. Then, full-mouth clinical parameters of
oral health were assessed, including periodontal, oral mucosal, and caries
status. RESULTS: The sensitivity and specificity of the test for bleeding on
probing were 71.8% and 77.5%, respectively (P = 0.05); for >=1 site with probing
depth (PD) >=4 mm, 48.3% and 100% (P <0.001); for >=2 sites with PD >=4 mm, 63.6%
and 100% (P <0.001); and for >2 sites with PD >=4 mm, 76.5% and 96.7% (P <0.01).
Regarding periodontitis (>=1 site with PD >=4 mm), hardly any false-positive
results were identified. The sensitivity of the immunoassay for >=1 caries
lesions was 76.5%, and the specificity was 96.7% (P <0.01). CONCLUSIONS: In 5
minutes, the aMMP-8 chairside test showed promising results, recognizing oral
inflammatory burden in adolescents with early initial signs of periodontitis.
Caries lesions could also be detected, but less efficiently.
PMID- 26430927
TI - Microbial Profiling in Experimentally Induced Biofilm Overgrowth Among Patients
With Various Periodontal States.
AB - BACKGROUND: This study measures microbial composition changes during biofilm
overgrowth and subsequent removal among patients with various states of
periodontal disease. METHODS: In this prospective cohort study, 175 participants
with various periodontal states (five biofilm-gingival interface [BGI] groups)
abstained from oral hygiene while using an acrylic stent. At day 21, participants
reinstituted oral hygiene and were followed for 4 weeks. Clinical parameters were
recorded, and subgingival plaque samples were analyzed at baseline, peak of
induction (day 21), and resolution using 16S rRNA probes (human oral microbe
identification microarray [HOMIM]). Using the change score (peak at induction
minus baseline) for bleeding on probing and probing depth (PD), the patients were
separated into high and low clinical responders. RESULTS: At baseline,
synergistetes were more abundant in moderate and severe periodontitis (BGI-P2 and
-P3) compared to mild periodontitis (BGI-P1), health (BGI-H), and gingivitis (BGI
G) (P = 0.005). Overall, at day 21 there was an increase in HOMIM scores of
firmicutes (P <=0.001), fusobacteria (P = 0.003), proteobacteria (P <=0.001),
synergistetes (P = 0.04), and bacteroidetes (P <=0.001). At resolution, these
phyla returned to baseline, except for synergistetes. Levels of synergistetes
were significantly higher at day 21 (P <=0.0001) and resolution (P = 0.0002) for
high clinical responders compared to low responders. CONCLUSION: The association
of synergistetes as a baseline predictor of incident PD increase, as well as the
higher levels at day 21, indicates a pathogenic role for these organisms in
disease progression in addition to the previously characterized fusobacteria,
proteobacteria, firmicutes, and bacteroidetes.
PMID- 26430928
TI - Comparison of Clinical and Radiographic Periodontal Status Between Habitual Water
Pipe Smokers and Cigarette Smokers.
AB - BACKGROUND: There is a dearth of studies that have compared clinical and
radiologic markers of periodontal inflammation between water-pipe smokers (WPs)
and cigarette smokers (CSs). The aim of the present study is to compare the
clinical and radiographic periodontal status between habitual WPs and CSs.
METHODS: In total, 200 males (50 WPs, 50 CSs, and 100 controls) with comparable
mean age and education were included. Demographic information was recorded using
a questionnaire. Periodontal parameters (plaque index [PI], bleeding on probing
[BOP], probing depth [PD], clinical attachment loss [AL], and marginal bone loss
[MBL]) and numbers of missing teeth (MT) were recorded. RESULTS: The duration of
each smoking session for WPs and CSs was 50.2 +/- 6.7 and 15.3 +/- 0.4 minutes,
respectively. Number of MT [P <0.0001], PI [P <0.0001], AL [P <0.0001], PD >=4 mm
[P <0.0001], and MBL [P <0.0001]) was significantly higher among WPs and CSs than
controls. BOP was significantly higher among controls than WPs (P <0.0001) and
CSs (P <0.0001). There was no statistically significant difference in the
aforementioned parameters between WPs and CSs. CONCLUSIONS: Males in a Saudi
Arabian community who were CSs or WPs had more MT and poorer periodontal
condition than never smokers. The periodontal condition of WPs was equally as
poor as CSs. Additional clinical observational studies with emphasis on sex and
sociodemographic characteristics are needed.
PMID- 26430929
TI - The Consumption of Synbiotic Bread Containing Lactobacillus sporogenes and Inulin
Affects Nitric Oxide and Malondialdehyde in Patients with Type 2 Diabetes
Mellitus: Randomized, Double-Blind, Placebo-Controlled Trial.
AB - OBJECTIVES: To our knowledge, no reports are available indicating the effects of
synbiotic bread consumption on nitric oxide (NO), biomarkers of oxidative stress,
and liver enzymes among patients with type 2 diabetes mellitus (T2DM). This study
was performed to determine the effects of the daily consumption of synbiotic
bread on NO, biomarkers of oxidative stress, and liver enzymes in patients with
T2DM. METHODS: This randomized, double-blind, placebo-controlled trial was
performed among 81 patients with diabetes, aged 35-70 years old. After a 2-week
run-in period, patients were randomly divided into 3 groups: group A (n = 27)
received synbiotic bread containing viable and the heat-resistant probiotic
Lactobacillus sporogenes (1 * 108 CFU) and 0.07 g inulin per 1 g, group B (n =
27) received probiotic bread containing Lactobacillus sporogenes (1 * 108 CFU),
and group C (n = 27) received control bread for 8 weeks. Patients were asked to
consume the synbiotic, probiotic, or control breads 3 times a day in 40 g
packages for a total of 120 g/day. Fasting blood samples were taken at baseline
and after an 8-week intervention for quantificationof related markers. RESULTS:
After 8 weeks, the consumption of synbiotic bread compared to the probiotic and
control breads resulted in a significant rise in plasma NO (40.6 +/- 34.4 vs 18.5
+/- 36.2 and -0.8 +/- 24.5 umol/L, respectively, p < 0.001) and a significant
reduction in malondialdehyde (MDA) levels (-0.7 +/- 0.7 vs 0.6 +/- 1.7 and 0.5 +/
1.5 umol/L, respectively, p = 0.001). We did not find any significant effect of
the synbiotic bread consumption on plasma total antioxidant capacity (TAC),
plasma glutathione (GSH), catalase, serum liver enzymes, calcium, iron, magnesium
levels, and blood pressure compared to the probiotic and control breads.
CONCLUSION: In conclusion, consumption of the synbiotic bread for 8 weeks among
patients with T2DM had beneficial effects on plasma NO and MDA levels; however,
it did not affect plasma TAC, GSH, catalase levels, serum liver enzymes, calcium,
iron, magnesium levels, and blood pressure.
PMID- 26430938
TI - Inconsistent handers show higher psychopathy than consistent handers.
AB - Three hundred and forty-two university students completed the Short Dark Triad
(SD3) and the Edinburgh Handedness Inventory (EHI). Inconsistent handers showed
higher psychopathy scores than consistent handers, and no handedness differences
were observed for narcissism or Machiavellianism. Participants were further
subdivided by quartile into low, moderately low, moderately high, and high
psychopathy groups (non-clinical). Absolute EHI scores were equally distributed
among low and moderate groups, but were significantly lower for the high
psychopathy group. These findings suggest that inconsistent handedness is only
associated with the upper quartile of psychopathy scores. Also, males showed
significantly higher psychopathy scores than females, and the ratio of male to
female inconsistent handers decreased as psychopathy score increased. No gender *
handedness interaction indicated that both female and male inconsistent handers
have higher psychopathy scores than consistent handers. Although significant, the
effects were small and 99.6% of participants were not in the range of a potential
clinical diagnosis. The reader, therefore, is strongly cautioned against equating
inconsistent handedness with psychopathy.
PMID- 26430939
TI - Low Prevalence of Carbapenem-Resistant Bacteria in River Water: Resistance Is
Mostly Related to Intrinsic Mechanisms.
AB - Carbapenems are last-resort antibiotics to handle serious infections caused by
multiresistant bacteria. The incidence of resistance to these antibiotics has
been increasing and new resistance mechanisms have emerged. The dissemination of
carbapenem resistance in the environment has been overlooked. The main goal of
this research was to assess the prevalence and diversity of carbapenem-resistant
bacteria in riverine ecosystems. The presence of frequently reported
carbapenemase-encoding genes was inspected. The proportion of imipenem-resistant
bacteria was on average 2.24 CFU/ml. Imipenem-resistant strains (n=110) were
identified as Pseudomonas spp., Stenotrophomonas maltophilia, Aeromonas spp.,
Chromobacterium haemolyticum, Shewanella xiamenensis, and members of
Enterobacteriaceae. Carbapenem-resistant bacteria were highly resistant to other
beta-lactams such as quinolones, aminoglycosides, chloramphenicol, tetracyclines,
and sulfamethoxazole/trimethoprim. Carbapenem resistance was mostly associated
with intrinsically resistant bacteria. As intrinsic resistance mechanisms, we
have identified the blaCphA gene in 77.3% of Aeromonas spp., blaL1 in all S.
maltophilia, and blaOXA-48-like in all S. xiamenensis. As acquired resistance
mechanisms, we have detected the blaVIM-2 gene in six Pseudomonas spp. (5.45%).
Integrons with gene cassettes encoding resistance to aminoglycosides (aacA and
aacC genes), trimethoprim (dfrB1b), and carbapenems (blaVIM-2) were found in
Pseudomonas spp. Results suggest that carbapenem resistance dissemination in
riverine ecosystems is still at an early stage. Nevertheless, monitoring these
aquatic compartments for the presence of resistance genes and its host organisms
is essential to outline strategies to minimize resistance dissemination.
PMID- 26430940
TI - Antibiotic Resistance, Virulence, and Genetic Background of Community-Acquired
Uropathogenic Escherichia coli from Algeria.
AB - The aim of the study was to investigate antibiotic resistance mechanisms,
virulence traits, and genetic background of 150 nonrepetitive community-acquired
uropathogenic Escherichia coli (CA-UPEC) from Algeria. A rate of 46.7% of
isolates was multidrug resistant. bla genes detected were blaTEM (96.8% of
amoxicillin-resistant isolates), blaCTX-M-15 (4%), overexpressed blaAmpC (4%),
blaSHV-2a, blaTEM-4, blaTEM-31, and blaTEM-35 (0.7%). All tetracycline-resistant
isolates (51.3%) had tetA and/or tetB genes. Sulfonamides and trimethoprim
resistance genes were sul2 (60.8%), sul1 (45.9%), sul3 (6.7%), dfrA14 (25.4%),
dfrA1 (18.2%), dfrA12 (16.3%), and dfrA25 (5.4%). High-level fluoroquinolone
resistance (22.7%) was mediated by mutations in gyrA (S83L-D87N) and parC (S80I
E84G/V or S80I) genes. qnrB5, qnrS1, and aac(6')-Ib-cr were rare (5.3%). Class 1
and/or class 2 integrons were detected (40.7%). Isolates belonged to phylogroups
B2+D (50%), A+B1 (36%), and F+C+Clade I (13%). Most of D (72.2%) and 38.6% of B2
isolates were multidrug resistant; they belong to 14 different sequence types,
including international successful ST131, ST73, and ST69, reported for the first
time in the community in Algeria and new ST4494 and ST4529 described in this
study. Besides multidrug resistance, B2 and D isolates possessed virulence
factors of colonization, invasion, and long-term persistence. The study
highlighted multidrug-resistant CA-UPEC with high virulence traits and an
epidemic genetic background.
PMID- 26430941
TI - Biocide Susceptibility of Staphylococcus aureus CC398 and CC30 Isolates from Pigs
and Identification of the Biocide Resistance Genes, qacG and qacC.
AB - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA), in particular
clonal complex (CC) 398, is increasingly found in livestock. Recently, MRSA CC30
was identified in Danish pigs. We determined the susceptibility of porcine S.
aureus isolates of CC398 and CC30 to disinfectants used in pig farming
(benzalkonium chloride, hydrogen peroxide, formaldehyde, sodium hypochlorite, and
caustic soda). Furthermore, efflux pump activity, antimicrobial resistance
profiles, hemolysis properties, and the presence of toxic shock syndrome toxin-1
(TSST-1) and Panton-Valentine Leukocidin (PVL)-encoding virulence factors were
investigated. METHODS: Susceptibilities to biocides and antimicrobial agents of
79 porcine S. aureus isolates were determined by the microdilution method.
Isolates comprised 21 methicillin-sensitive S. aureus (MSSA) and 40 MRSA isolates
belonging to CC398 and 13 MSSA and 5 MRSA isolates belonging to CC30. The
presence of quaternary ammonium compound (QAC) resistance efflux pumps was
analyzed using an ethidium bromide accumulation assay. The presence of qac
resistance genes in active efflux pump positive isolates was determined by whole
genome sequencing data. All isolates were screened for lukPV and tst genes with
PCR, and hemolytic activities were determined using an agar plate assay. RESULTS:
S. aureus isolates did not show reduced susceptibility to the biocides tested.
However, the QAC resistance gene, qacG, was detected in three MRSA CC30 isolates
and the qacC in one MRSA CC30 isolate. CC30 isolates were generally more
susceptible to non-beta-lactam antibiotics than CC398. Isolates generally had low
hemolytic activity and none encoded PVL or TSST-1. CONCLUSION: The presence of
qac genes in European porcine S. aureus isolates and in livestock-associated MRSA
CC30 is for the first time described in this study. This finding is concerning as
it ultimately may compromise disinfection with QACs and thereby contribute to the
selection and spread of MRSA CC30.
PMID- 26430942
TI - Increasing Trend of Heterogeneous Vancomycin Intermediate Staphylococcus aureus
in a Tertiary Care Center of Northern India.
AB - Heterogeneous vancomycin intermediate Staphylococcus aureus (hVISA) strains are
increasingly reported, and their association with vancomycin treatment failure is
a well-known problem worldwide. A total of 500 clinical isolates of methicillin
resistant S. aureus were screened for hVISA by four different methods from May
2011 to May 2014. The number of strains screened for hVISA from May to April in
2011-2012, 2012-2013, and 2013-2014 were 198, 123, and 179, respectively. hVISA
strains were studied by transmission electron microscopy (TEM) for cell wall
thickness and also for their ability to form biofilm on a polystyrene microtiter
plate. hVISA strains detected by four different methods-brain heart infusion agar
with vancomycin with 4 mg/L/gradient plate/macro E-test/and glycopeptide
resistance detection (GRD) E test-were as follows: 11.6%/10%/9%, and 9.5% in 2011
2012, 12.1%/9.7%/8.9%, and 10.5% in 2012-2013, and 13.9%/11.7%/11.1%, and 12.8%
in 2013-2014, respectively. Population analysis profile-area under curve analysis
confirmed hVISA in 4.5% (9/198), 6.5% (8/123), and 6.7% (12/179) in respective
years; 24% (7/29) of hVISA isolates were nonsusceptible to daptomycin. TEM showed
a significant increase in cell wall thickness of hVISA isolates (p<0.001) with a
distinct reduction in their biofilm formation ability.
PMID- 26430943
TI - Susceptibility of Group A Streptococcus to Antimicrobial Agents in Northern
Israel: A Surveillance Study.
AB - BACKGROUND: Resistant pathogens are an increasing threat affecting millions of
people globally. More complicated patients are presented with pathogens harboring
new resistance mechanisms, while the pipeline of new antimicrobials hardly
proposes solutions. In such a scenario, more severely ill patients remain with no
adequate treatment to offer. In addition, massive misuse of antimicrobials,
including excessive length of treatment or wrong dosage, also contributes to
increasing the rate of pathogens resistance to antimicrobials. Isolation of
Streptococcus pyogenes (Group A Streptococcus-GAS) is the main indication for
antibiotic treatment to patients diagnosed with acute tonsillitis. Hence, GAS
resistance to antibiotics requires periodic monitoring. OBJECTIVES: To assess
susceptibility rates of GAS to penicillin, macrolides, clindamycin, and
tetracycline in northern Israel and to compare the findings to the high
antimicrobial susceptibility of GAS isolates reported in the same region in 2004
and to other geographical areas. METHODS: Throat samples from 300 outpatients
were collected and cultured at the regional laboratory of Emek Medical Center
during September to October 2011. RESULTS: In 300 samples, the susceptibility
rates of GAS to penicillin, erythromycin, azithromycin, clindamycin, and
tetracycline in northern Israel still remain very high. CONCLUSIONS: Continuous
control of antimicrobials usage and periodic surveillance of susceptibility
rates, together with educational programs and appropriate and targeted treatment
protocols, are essential and highly recommended to keep these high susceptibility
rates for as long as possible.
PMID- 26430945
TI - Design of Pore Size and Functionality in Pillar-Layered Zn-Triazolate
Dicarboxylate Frameworks and Their High CO2/CH4 and C2 Hydrocarbons/CH4
Selectivity.
AB - In the design of new materials, those with rare and exceptional compositional and
structural features are often highly valued and sought after. On the other hand,
materials with common and more accessible modes can often provide richer and
unsurpassed compositional and structural variety that makes them a more suitable
platform for systematically probing the composition-structure-property
correlation. We focus here on one such class of materials, pillar-layered metal
organic frameworks (MOFs), because different pore size and shape as well as
functionality can be controlled and adjusted by using pillars with different
geometrical and chemical features. Our approach takes advantage of the readily
accessible layered Zn-1,2,4-triazolate motif and diverse dicarboxylate ligands
with variable length and functional groups, to prepare seven Zn-triazolate
dicarboxylate pillar-layered MOFs. Six different gases (N2, H2, CO2, C2H2, C2H4,
and CH4) were used to systematically examine the dependency of gas sorption
properties on chemical and geometrical properties of those MOFs as well as their
potential applications in gas storage and separation. All of these pillar-layered
MOFs show not only remarkable CO2 uptake capacity, but also high CO2 over CH4 and
C2 hydrocarbons over CH4 selectivity. An interesting observation is that the BDC
ligand (BDC = benzenedicarboxylate) led to a material with the CO2 uptake
outperforming all other metal-triazolate-dicarboxylate MOFs, even though most of
them are decorated with amino groups, generally believed to be a key factor for
high CO2 uptake. Overall, the data show that the exploration of the synergistic
effect resulting from combined tuning of functional groups and pore size may be a
promising strategy to develop materials with the optimum integration of
geometrical and chemical factors for the highest possible gas adsorption capacity
and separation performance.
PMID- 26430944
TI - Characteristics and Outcomes of Acinetobacter baumannii Infections in Critically
Ill Patients with Cancer: A Matched Case-Control Study.
AB - AIM: To describe the characteristics and outcomes of Acinetobacter baumannii (AB)
infections in critically ill cancer patients and to evaluate the impact of AB on
mortality and length of stay (LOS). RESULTS: In a 4-year case-control study of
critically ill cancer patients, we identified 161 patients with AB infections and
232 matched patients who were treated in the intensive care unit (ICU) during the
same time period, but had no AB cultures. The case and control groups were
matched for APACHE II, age, gender, type of malignancy, and mechanical
ventilation. Most AB isolates were carbapenem-resistant (n=142, 88.2%). The
majority of positive cultures were collected from the respiratory tract (58%) and
blood (21.8%). The median ICU LOS and mortality rate for patients with AB
infections were higher than those for the control group (12 days [IQR 6-23] vs. 3
days [IQR 1-7], p<0.0001 and 73.3% vs. 61.5%, p=0.015, respectively). AB
infection was independently associated with ICU LOS and mortality: OR 1.108 (95%
CI, 1.077-1.139), OR 1.658 (95% CI, 1.017-2.703), respectively. CONCLUSION: AB
infections in critically ill cancer patients were independently associated with
increased mortality and increased ICU LOS. Measures to improve the outcomes of
critically ill cancer patients infected with AB are necessary.
PMID- 26430946
TI - Corrigendum: Simple Copy Number Determination with Reference Query Pyrosequencing
(RQPS).
PMID- 26430947
TI - Evidence Base Update for Autism Spectrum Disorder.
AB - This evidence base update examines the level of empirical support for
interventions for children with autism spectrum disorder (ASD) younger than 5
years old. It focuses on research published since a previous review in this
journal (Rogers & Vismara, 2008 ). We identified psychological or behavioral
interventions that had been manualized and evaluated in either (a) experimental
or quasi-experimental group studies or (b) systematic reviews of single-subject
studies. We extracted data from all studies that met these criteria and were
published after the previous review. Interventions were categorized across two
dimensions. First, primary theoretical principles included applied behavior
analysis (ABA), developmental social-pragmatic (DSP), or both. Second, practice
elements included scope (comprehensive or focused), modality (individual
intervention with the child, parent training, or classrooms), and intervention
targets (e.g., spoken language or alternative and augmentative communication). We
classified two interventions as well-established (individual, comprehensive ABA
and teacher-implemented, focused ABA + DSP), 3 as probably efficacious
(individual, focused ABA for augmentative and alternative communication;
individual, focused ABA + DSP; and focused DSP parent training), and 5 as
possibly efficacious (individual, comprehensive ABA + DSP; comprehensive ABA
classrooms; focused ABA for spoken communication; focused ABA parent training;
and teacher-implemented, focused DSP). The evidence base for ASD interventions
has grown substantially since 2008. An increasing number of interventions have
some empirical support; others are emerging as potentially efficacious.
Priorities for future research include improving outcome measures, developing
interventions for understudied ASD symptoms (e.g., repetitive behaviors),
pinpointing mechanisms of action in interventions, and adapting interventions for
implementation with fidelity by community providers.
PMID- 26430948
TI - Psychological Science and Innovative Strategies for Informing Health Care
Redesign: A Policy Brief.
AB - Recent health care legislation and shifting health care financing strategies are
transforming health and behavioral health (a broad term referring to mental
health, substance use, and health behavior) care in the United States. Advances
in knowledge regarding effective treatment and services coupled with incentives
for innovation in health and behavioral health care delivery systems make this a
unique time for mobilizing our science to enhance the success of health and
behavioral health care redesign. To optimize the potential of our current health
care environment, a team was formed composed of leaders from the Societies of
Clinical Child & Adolescent Psychology, Pediatric Psychology, and Child and
Family Policy and Practice (Divisions 53, 54, and 37 of the American
Psychological Association). This team was charged with reviewing the scientific
and policy literature with a focus on five major issues: (a) improving access to
care and reducing health disparities, (b) integrating behavioral health care
within primary care, (c) preventive services, (d) enhancing quality and outcomes
of care, and (e) training and workforce development. The products of that work
are summarized here, including recommendations for future research, clinical,
training, and policy directions. We conclude that the current emphasis on
accountable care and evaluation of the outcomes of care offer numerous
opportunities for psychologists to integrate science and practice for the benefit
of our children, families, and nation. The dramatic changes that are occurring in
psychological and behavioral health care services and payment systems also
require evolution in our practice and training models.
PMID- 26430951
TI - Factor structure and invariance test of the alcohol use disorder identification
test (AUDIT): Comparison and further validation in a U.S. and Philippines college
student sample.
AB - The Alcohol Use Disorder Identification Test's factor structure varies depending
on population and culture. Because of this inconsistency, this article examined
the factor structure of the test and conducted a factorial invariance test
between a U.S. and a Philippines college sample. Confirmatory factor analyses
indicated that a three-factor solution outperforms the one- and two-factor
solution in both samples. Factorial invariance analyses further supports the
confirmatory findings by showing that factor loadings were generally invariant
across groups; however, item intercepts show non-invariance. Country differences
between factors show that Filipino consumption factor mean scores were
significantly lower than their U.S. counterparts.
PMID- 26430952
TI - Association of treatment factors with surgical outcomes in tri-modality therapy
for esophageal cancer.
AB - BACKGROUND AND OBJECTIVES: To identify the impact of the interval between
chemoradiation to surgery on morbidity and mortality in patients undergoing tri
modality therapy for esophageal cancer. METHODS: Eighty-five patients completed
chemoradiation followed by esophagectomy between 2006 and 2011. The interval
between completion of chemoradiation and surgery was calculated for each patient.
We evaluated the association of quartiles and 3-week groups with morbidity and
mortality using logistic regression. Other treatment and clinical factors were
also assessed. RESULTS: A total of 59 patients(69%) experienced at least one
complication. When examining specific complications, patients with pulmonary
complications had a longer mean time interval from chemoradiation to surgery (P =
0.02). Linear regression showed an association between longer interval between
chemoradiation to surgery and hospital length of stay (LOS) >14 days when
analyzing by both interval quartile (P = 0.04) and 3-week intervals (P = 0.04).
On multivariable analysis, increased time interval predicted for pulmonary
complications (P < 0.01) and LOS >14 days (P = 0.03). When examining other
treatment factors, squamous cell histology (P = 0.02) also predicted for a
hospital length of stay >14 days. CONCLUSIONS: Factors such as interval between
completion of chemoradiation and surgery and squamous cell histology may be
associated with surgical morbidity. Further data is warranted to confirm these
findings.
PMID- 26430953
TI - Leptospirosis: a report on a series of five autochthonous cases in a Greek
region.
AB - Leptospirosis is a worldwide zoonotic disease difficult to diagnose both to the
clinic and the laboratory. Many risk factors have been involved, such as
planting, hunting, harvesting and butchering or sports, such as rafting. We
reported our experience through a period of 20 months and we tried to
investigate prognostic factors predicting clinical outcomes. Five male patients
were admitted to our Department with a median age of 40 years. Overall, three
out of five patients presented to other hospital and were transferred to ours
with a wrong or delayed diagnosis. In terms of clinical signs and symptoms, all
presented with fever, myalgia, headache and jaundice, whereas conjunctival
suffusion was present in 80% of them. Acute renal injury and liver deficiency
were diagnosed in all subjects. Acute renal failure management required dialysis
in 3/5 patients, whereas renal recovery was achieved soon after clinical
improvement. However, clinical awareness and serology are the most important
tools for accurate and quick diagnosis in order to administer the appropriate
therapy.
PMID- 26430954
TI - Valence Virtual Orbitals: An Unambiguous ab Initio Quantification of the LUMO
Concept.
AB - Many chemical concepts hinge on the notion of an orbital called the lowest
unoccupied molecular orbital, or LUMO. This hypothetical orbital and the much
more concrete highest occupied molecular orbital (HOMO) constitute the two
"frontier orbitals", which rationalize a great deal of chemistry. A viable LUMO
candidate should have a sensible energy value, a realistic shape with amplitude
on those atoms where electron attachment or reduction or excitation processes
occur, and often an antibonding correspondence to one of the highest occupied
MOs. Unfortunately, today's quantum chemistry calculations do not yield useful
empty orbitals. Instead, the empty canonical orbitals form a large sea of
orbitals, where the interesting valence antibonds are scrambled with the basis
set's polarization and diffuse augmentations. The LUMO is thus lost within a
continuum associated with a detached electron, as well as many Rydberg excited
states. A suitable alternative to the canonical orbitals is proposed, namely, the
valence virtual orbitals. VVOs are found by a simple algorithm based on singular
value decomposition, which allows for the extraction of all valence-like orbitals
from the large empty canonical orbital space. VVOs are found to be nearly
independent of the working basis set. The utility of VVOs is demonstrated for
construction of qualitative MO diagrams, for prediction of valence excited
states, and as starting orbitals for more sophisticated calculations. This
suggests that VVOs are a suitable realization of the LUMO, LUMO + 1, ... CONCEPT:
VVO generation requires no expert knowledge, as the number of VVOs sought is
found by counting s-block atoms as having only a valence s orbital, transition
metals as having valence s and d, and main group atoms as being valence s and p
elements. Closed shell, open shell, or multireference wave functions and elements
up to xenon may be used in the present program.
PMID- 26430956
TI - New and Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine
Tumors.
AB - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare, generally
indolent neoplasms that can arise throughout the gastrointestinal system. Some
GEP-NETs, known as functional, secrete hormones that can lead to a complex of
symptoms. Classical carcinoid syndrome is associated with flushing, diarrhea,
bronchospasm, and symptoms of valvular heart disease. GEP-NETs are classified
according to the primary tumor site, functionality of the disease, and histology.
Treatment is guided by the resectability of the tumor, the location and extent of
metastases, and the presence of clinical symptoms. Typically, first-line
treatment of patients with unresectable disease includes the use of somatostatin
analogs, such as octreotide LAR depot or lanreotide depot/autogel, which was
recently approved by the US Food and Drug Administration for treatment of GEP
NETs. Somatostatin analogs can improve the severe diarrhea/flushing episodes that
may be associated with metastatic carcinoid tumors. For patients with pancreatic
NETs, additional approved treatment options include the targeted agents
everolimus and sunitinib, which have demonstrated antitumor activity.
Chemotherapy may also have a selective role, particularly in pancreatic NETs.
Localized approaches, including cytoreductive surgery, hepatic arterial
embolization, and ablative therapies, may be used for palliative treatment in
patients with liver metastases.
PMID- 26430960
TI - Solvent Structure around Lanthanoid(III) Ions in Liquid DMSO As Revealed by
Polarizable Molecular Dynamics Simulations.
AB - We present a study of the solvation of lanthanoid(III) ions in liquid dimethyl
sulfoxide (DMSO) using molecular dynamics simulations employing a newly developed
polarizable force field. The van der Waals (vdW) parameters were obtained for
La(3+) and Lu(3+) (the first and the last in the lanthanoid(III) series) using ab
initio data. The parameters of the other ions can be extrapolated based on
physical considerations without additional (and costly) quantum chemistry
calculations. This extrapolation procedure has been successfully applied to
Gd(3+). The outcomes of our simulations turn out to be in agreement with both the
experimental data available in the literature and the ab initio results. A small
adjustment of the vdW parameters further increases the agreement with experiments
and has allowed us to provide structures, geometrical parameters, and
coordination numbers. For heavy lanthanoids (Gd and Lu) we obtain clearly an 8
fold coordination, with a distorted square antiprism (SAP) geometry in agreement
with EXAFS and XANES experiments; for the La(3+) ion, our force field predicts a
mixed situation with both the 8-fold SAP and 9-fold geometry where the SAP
structure is capped by a ninth molecule added over one face.
PMID- 26430955
TI - Silica-Supported Oligomeric Benzyl Phosphate (Si-OBP) and Triazole Phosphate (Si
OTP) Alkylating Reagents.
AB - The syntheses of silica-supported oligomeric benzyl phosphates (Si-OBP(n)) and
triazole phosphates (Si-OTP(n)) using ring-opening metathesis polymerization
(ROMP) for use as efficient alkylating reagents is reported. Ease of synthesis
and grafting onto the surface of norbornenyl-tagged (Nb-tagged) silica particles
has been demonstrated for benzyl phosphate and triazole phosphate monomers. It is
shown that these silica polymer hybrid reagents, Si-OBP(n) and Si-OTP(n), can be
used to carry out alkylation reactions with an array of different nucleophiles to
afford the corresponding benzylated and (triazolyl)methylated products in good
yield and high purity.
PMID- 26430961
TI - Overexpression of caldesmon is associated with tumor progression in patients with
primary non-muscle-invasive bladder cancer.
AB - The expression and function of caldesmon (CAD) in urothelial bladder carcinoma
(BC) have not been reported. Here, we investigated the expression, prognostic
value, and potential functional mechanism of CAD in primary non-muscle-invasive
bladder cancer (NMIBC). Protein profiling of tissue samples using antibody
microarrays showed significantly higher CAD expression in muscle-invasive BC
tissues compared with NMIBC tissues. We then validated the CAD expression in BC
cells by immunohistochemistry analysis using paraffin-embedded tissue blocks and
western blots using BC cell lines. In addition, we examined the expression of CAD
variants by reverse transcription-polymerase chain reaction, and confirmed the
expression of low-molecular-weight isoforms (L-CAD), specifically encoded by WI
38 L-CAD II (transcript variant 2), in BC cells. Survival analysis in an
independent primary NMIBC cohort comprising 132 patients showed that positive CAD
expression was significantly associated with poorer prognosis than no CAD
expression with regard to recurrence- and progression-free survival (p = 0.001
and 0.014, respectively). Multivariate analyses further indicated that positive
CAD expression was an independent predictor of progression-free survival (p =
0.032; HR = 5.983). Data obtained from in vitro silencing and overexpression
studies indicated that L-CAD promotes migration and invasiveness of BC cells.
Immunofluorescence assays showed dramatic structural changes in the actin
cytoskeleton of BC cells after L-CAD overexpression. Our findings collectively
suggest that L-CAD overexpression in primary NMIBC is significantly associated
with tumor progression and that a possible mechanism for L-CAD's activity is
implicated in increased cell motility and invasive characteristics through
morphological changes in BC cells.
PMID- 26430962
TI - Protein kinase CK2alpha catalytic subunit is overexpressed and serves as an
unfavorable prognostic marker in primary hepatocellular carcinoma.
AB - Protein kinase CK2 alpha (CK2alpha), one isoform of the catalytic subunit of
serine/threonine kinase CK2, has been indicated to participate in tumorigenesis
of various malignancies. We conducted this study to investigate the biological
significances of CK2alpha expression in hepatocellular carcinoma (HCC)
development. Real-time quantitative polymerase and western blotting analyses
revealed that CK2alpha expression was significantly increased at mRNA and protein
levels in HCC tissues. Immunohistochemical analyses indicated that amplified
expression of CK2alpha was highly correlated with poor prognosis. And functional
analyses (cell proliferation and colony formation assays, cell migration and
invasion assays, cell cycle and apoptosis assays) found that CK2alpha promoted
cell proliferation, colony formation, migration and invasion, as well as
inhibited apoptosis in hepatoma cell lines in vitro. CK2alpha-silenced resulted
in significant apoptosis in cells that was demonstrated been associated with
downregulation of expression of Bcl-2, p-AKT (ser473) and upregulation of
expression of total P53, p-P53, Bax, caspase3 and cleaved-caspase3 in HCC cells.
In addition, experiments with a mouse model revealed that the stimulative effect
of CK2alpha on tumorigenesis in nude mice. Our results suggest that CK2alpha
might play an oncogenic role in HCC, and therefore it could serve as a biomarker
for prognostic and therapeutic applications in HCC.
PMID- 26430963
TI - The transcription factor c-Fos coordinates with histone lysine-specific
demethylase 2A to activate the expression of cyclooxygenase-2.
AB - Cyclooxygenase-2 (COX-2) is overexpressed in a variety of human epithelial
cancers, including lung cancer, and is highly associated with a poor prognosis
and a low survival rate. Understanding how COX-2 is regulated in response to
carcinogens will offer insight into designing anti-cancer strategies and
preventing cancer development. Here, we analyzed COX-2 expression in several
human lung cancer cell lines and found that COX-2 expression was absent in the
H719 and H460 cell lines by a DNA methylation-independent mechanism. The re
expression of COX-2 was observed after 12-O-tetradecanoylphorbol-13-acetate (TPA)
treatment in both cell lines. Further investigation found that H3K36
dimethylation was significantly reduced near the COX-2 promoter because histone
demethylase 2A (KDM2A) was recruited to the COX-2 promoter after TPA treatment.
In addition, the transcription factor c-Fos was found to be required to recruit
KDM2A to the COX-2 promoter for reactivation of COX-2 in response to TPA
treatment in both the H719 and H460 cell lines. Together, our data reveal a novel
mechanism by which the carcinogen TPA activates COX-2 expression by regulating
H3K36 dimethylation near the COX-2 promoter.
PMID- 26430964
TI - Overexpression of Bcl-2 induces STAT-3 activation via an increase in
mitochondrial superoxide.
AB - We recently reported a novel interaction between Bcl-2 and Rac1 and linked that
to the ability of Bcl-2 to induce a pro-oxidant state in cancer cells. To gain
further insight into the functional relevance of this interaction, we utilized
computer simulation based on the protein pathway dynamic network created by
Cellworks Group Inc. STAT3 was identified among targets that positively
correlated with Rac1 and/or Bcl-2 expression levels. Validating this, the
activation level of STAT3, as marked by p-Tyr705, particularly in the
mitochondria, was significantly higher in Bcl-2-overexpressing cancer cells. Bcl
2-induced STAT3 activation was a function of GTP-loaded Rac1 and NADPH oxidase
(Nox)-dependent increase in intracellular superoxide (O2*-). Furthermore, ABT199,
a BH-3 specific inhibitor of Bcl-2, as well as silencing of Bcl-2 blocked STAT3
phosphorylation. Interestingly, while inhibiting intracellular O2*- blocked STAT3
phosphorylation, transient overexpression of wild type STAT3 resulted in a
significant increase in mitochondrial O2*- production, which was rescued by the
functional mutants of STAT3 (Y705F). Notably, a strong correlation between the
expression and/or phosphorylation of STAT3 and Bcl-2 was observed in primary
tissues derived from patients with different sub-sets of B cell lymphoma. These
data demonstrate the presence of a functional crosstalk between Bcl-2, Rac1 and
activated STAT3 in promoting a permissive redox milieu for cell survival. Results
also highlight the potential utility of a signature involving Bcl-2
overexpression, Rac1 activation and STAT3 phosphorylation for stratifying
clinical lymphomas based on disease severity and chemoresistance.
PMID- 26430965
TI - A functional variant in HOXA11-AS, a novel long non-coding RNA, inhibits the
oncogenic phenotype of epithelial ovarian cancer.
AB - The homeobox A (HOXA) region of protein-coding genes impacts female reproductive
system embryogenesis and ovarian carcinogenesis. The 5-prime end of HOXA includes
three long non-coding RNAs (lncRNAs) (HOXA10-AS, HOXA11-AS, and HOTTIP) that are
underexplored in epithelial ovarian cancer (EOC). We evaluated whether common
genetic variants in these lncRNAs are associated with EOC risk and/or have
functional roles in EOC development. Using genome-wide association study data
from 1,201 serous EOC cases and 2,009 controls, an exonic variant within HOXA11
AS, rs17427875 (A>T), was marginally associated with reduced serous EOC risk (OR
= 0.88 (95% CI: 0.78-1.01, p = 0.06). Functional studies of ectopic expression of
HOXA11-AS minor allele T in EOC cells showed decreased survival, proliferation,
migration, and invasion compared to common allele A expression. Additionally,
stable expression of HOXA11-AS minor allele T reduced primary tumor growth in
mouse xenograft models to a greater extent than common allele A. Furthermore,
HOXA11-AS expression levels were significantly lower in human EOC tumors than
normal ovarian tissues (p < 0.05), suggesting that HOXA11-AS has a tumor
suppressor function in EOC which may be enhanced by the T allele. These findings
demonstrate for the first time a role for HOXA11-AS in EOC with effects that
could be modified by germline variants.
PMID- 26430966
TI - Systemic delivery of HER2-retargeted oncolytic-HSV by mesenchymal stromal cells
protects from lung and brain metastases.
AB - Fully retargeted oncolytic herpes simplex viruses (o-HSVs) gain cancer
specificity from redirection of tropism to cancer-specific receptors, and are non
attenuated. To overcome the hurdles of systemic delivery, and enable oncolytic
viruses (o-viruses) to reach metastatic sites, carrier cells are being exploited.
Mesenchymal stromal cells (MSCs) were never tested as carriers of retargeted o
viruses, given their scarse-null expression of the cancer-specific receptors. We
report that MSCs from different sources can be forcedly infected with a HER2
retargeted oncolytic HSV. Progeny virus spread from MSCs to cancer cells in vitro
and in vivo. We evaluated the organ distribution and therapeutic efficacy in two
murine models of metastatic cancers, following a single i.v. injection of
infected MSCs. As expected, the highest concentration of carrier-cells and of
viral genomes was in the lungs. Viral genomes persisted throughout the body for
at least two days. The growth of ovarian cancer lung metastases in nude mice was
strongly inhibited, and the majority of treated mice appeared metastasis-free.
The treatment significantly inhibited also breast cancer metastases to the brain
in NSG mice, and reduced by more than one-half the metastatic burden in the
brain.
PMID- 26430968
TI - Can Computerized Neuropsychological Testing in the Emergency Department Predict
Recovery for Young Athletes With Concussions?
AB - OBJECTIVE: The objective of this study was to determine if computerized
neurocognitive testing (Immediate Post-Concussion Assessment and Cognitive
Testing [ImPACT]) in the emergency department (ED) can be used as a prognostic
tool to detect young athletes at risk of having protracted concussive symptoms.
METHODS: This was a prospective cohort study of athletes aged 11 to 18 years who
presented to an ED less than 24 hours after sustaining a sports-related
concussion. ImPACT was administered in the ED, and performance was categorized as
"poor" if the athlete had 3 (of 4) or greater low domain scores. Participants
completed the Post-Concussion Symptom Scale (PCSS) in the ED and by phone at 1
and 2 weeks after injury. Athletes were symptomatic if their PCSS score was more
than 6 in males and more than 8 in females. RESULTS: One hundred nine patients
were enrolled; 60% and 36% remained symptomatic at 1 and 2 weeks after injury,
respectively. "Poor" ImPACT performance was not particularly useful in predicting
athletes with protracted symptoms (at 1 week: positive predictive value, 70.8%;
negative predictive value, 43.5%; at 2 weeks: positive predictive value, 47.8%;
negative predictive value, 68.9%). In bivariate analysis, a higher ED PCSS score
was associated with protracted symptoms (at 1 week: odds ratio, 1.1 [confidence
interval, 1.0-1.1]; at 2 weeks: odds ratio, 1.0 [confidence interval, 1.0-1.1]).
CONCLUSIONS: Computerized neurocognitive testing in the ED has limited usefulness
in predicting protracted symptoms. Total acute symptom burden may be a useful
prognostic tool in the ED evaluation of concussed young athletes, yet further
research is necessary.
PMID- 26430967
TI - Novel Potent N-Methyl-d-aspartate (NMDA) Receptor Antagonists or sigma1 Receptor
Ligands Based on Properly Substituted 1,4-Dioxane Ring.
AB - Two series of 1,4-dioxanes (4-11 and 12-19) were rationally designed and prepared
to interact either with the phencyclidine (PCP) binding site of the N-methyl-d
aspartate (NMDA) receptor or with sigma1 receptors, respectively. The biological
profiles of the novel compounds were assessed using radioligand binding assays,
and the compounds with the highest affinities were investigated for their
functional activity. The results were in line with the available pharmacophore
models and highlighted that the 1,4-dioxane scaffold is compatible with potent
antagonist activity at NMDA receptor or high affinity for sigma1 receptors. The
primary amines 6b and 7 bearing a cyclohexyl and a phenyl ring or two phenyl
rings in position 6, respectively, were the most potent noncompetitive
antagonists at the NMDA receptor with IC50 values similar to those of the
dissociative anesthetic (S)-(+)-ketamine. The 5,5-diphenyl substitution
associated with a benzylaminomethyl moiety in position 2, as in 18, favored the
interaction with sigma1 receptors.
PMID- 26430969
TI - Localized Ion-Beam Irradiation-Induced Wrinkle Patterns.
AB - We observe a localized irradiation-induced wrinkle pattern on
poly(dimethylsiloxane) (PDMS) via a long pattern mask. Localized ion-beam
irradiation induces an inhomogeneous wrinkle pattern on the treated region. To
confirm the inhomogeneity of the entire wrinkle pattern, its morphology was
investigated using optical microscopy, which revealed separated regions in the
wrinkle pattern. We used atomic force microscopy for quantitative analysis of the
wrinkle pattern morphology and analyzed the angular distribution and the
direction of compressive stress of the irradiated area. We confirmed the
direction of stress release along the distance from the edges, and we achieved
control of the orientation of the wrinkle pattern by altering the width of the
irradiated area. Investigation of the inhomogeneities in a localized wrinkle
formation provides an understanding of the formation mechanism to enhance its
performance and application in various fields.
PMID- 26430970
TI - Characterization of the Leukocyte Response in Acute Vocal Fold Injury.
AB - Macrophages location in the superficial layer of the vocal fold (VF) is not only
at the first line of defense, but in a place of physiologic importance to voice
quality. This study characterizes and compares macrophage function in two models
of acute injury. Porcine VF injuries were created bilaterally by either surgical
biopsy or lipopolysaccharide (LPS) (1.5 MUg/kg) injection. Animals were
sacrificed at 1- or 5-day post LPS or 3-, 7-, or 23-days post-surgical injury (n
= 3/time/injury). Flow cytometry characterized immunophenotypes and RT-PCR
quantified cytokine gene expression. Uninjured VF were used as controls. Post
surgical and LPS injury, SWC9+/SWC3- cells identified as hi SLA-DR+ (p<0.05)
compared to controls along with hi CD16+ expression at 1-day and 3-days
respectively compared to all other time points (p<0.05). Surgical injuries,
SWC9+/SWC3- cells exhibited hi CD163+ (p<0.05) at 3-days along with upregulation
in TNFalpha and TGFbeta1 mRNA compared to 23-days (p<0.05). No measurable changes
to IL-12, IFNgamma, IL-10, IL-4 mRNA post-surgery. LPS injuries induced
upregulation of TNFalpha, IL-12, IFNgamma, IL-10, and IL-4 mRNA at 1- and 5-days
compared to controls (p<0.05). Higher levels of IL-10 mRNA were found 1-day post
LPS compared to 5-days (p<0.05). No changes to CD163 or CD80/86 post-LPS were
measured. Acute VF injuries revealed a paradigm of markers that appear to
associate with each injury. LPS induced a regulatory phenotype indicated by
prominent IL-10 mRNA expression. Surgical injury elicited a complex phenotype
with early TNFalpha mRNA and CD163+ and persistent TGFbeta1 transcript
expression.
PMID- 26430971
TI - Effects of Oil-Contaminated Sediments on Submerged Vegetation: An Experimental
Assessment of Ruppia maritima.
AB - Oil spills threaten the productivity of ecosystems through the degradation of
coastal flora and the ecosystem services these plants provide. While lab and
field investigations have quantified the response of numerous species of emergent
vegetation to oil, the effects on submerged vegetation remain uncertain. Here, we
discuss the implications of oil exposure for Ruppia maritima, one of the most
common species of submerged vegetation found in the region affected by the recent
Deepwater Horizon oil spill. We grew R. maritima in a range of manipulated
sediment oil concentrations: 0, 0.26, 0.53, and 1.05 mL oil /L tank volume, and
tracked changes in growth (wet weight and shoot density/length), reproductive
activity (inflorescence and seed production), root characteristics (mass, length,
diameter, and area), and uprooting force of plants. While no statistical
differences were detected in growth, plants exhibited significant changes to
reproductive output, root morphology, and uprooting force. We found significant
reductions in inflorescences and fruiting bodies at higher oil concentrations. In
addition, the roots growing in the high oil were shorter and wider. Plants in
medium and high oil required less force to uproot. A second experiment was
performed to separate the effects of root morphology and oiled sediment
properties and indicated that there were also changes to sediment cohesion that
contributed to a reduction in uprooting forces in medium and high oil. Given the
importance of sexual reproduction for these plants, oil contamination may have
substantial population-level effects. Moreover, areas containing buried oil may
be more susceptible to high energy storm events due to the reduction in uprooting
force of foundation species such as R. maritima.
PMID- 26430972
TI - Improving the Precision of Weak Measurements by Postselection Measurement.
AB - Postselected weak measurement is a useful protocol for amplifying weak physical
effects. However, there has recently been controversy over whether it gives any
advantage in precision. While it is now clear that retaining failed
postselections can yield more Fisher information than discarding them, the
advantage of postselection measurement itself still remains to be clarified. In
this Letter, we address this problem by studying two widely used estimation
strategies: averaging measurement results, and maximum likelihood estimation,
respectively. For the first strategy, we find a surprising result that squeezed
coherent states of the pointer can give postselected weak measurements a higher
signal-to-noise ratio than standard ones while all standard coherent states
cannot, which suggests that raising the precision of weak measurements by
postselection calls for the presence of "nonclassicality" in the pointer states.
For the second strategy, we show that the quantum Fisher information of
postselected weak measurements is generally larger than that of standard weak
measurements, even without using the failed postselection events, but the gap can
be closed with a proper choice of system state.
PMID- 26430973
TI - Majorana Braiding with Thermal Noise.
AB - We investigate the self-correcting properties of a network of Majorana wires, in
the form of a trijunction, in contact with a parity-preserving thermal
environment. As opposed to the case where Majorana bound states are immobile,
braiding Majorana bound states within a trijunction introduces dangerous error
processes that we identify. Such errors prevent the lifetime of the memory from
increasing with the size of the system. We confirm our predictions with Monte
Carlo simulations. Our findings put a restriction on the degree of self
correction of this specific quantum computing architecture.
PMID- 26430974
TI - Landauer's Principle in Multipartite Open Quantum System Dynamics.
AB - We investigate the link between information and thermodynamics embodied by
Landauer's principle in the open dynamics of a multipartite quantum system. Such
irreversible dynamics is described in terms of a collisional model with a finite
temperature reservoir. We demonstrate that Landauer's principle holds, for such a
configuration, in a form that involves the flow of heat dissipated into the
environment and the rate of change of the entropy of the system. Quite
remarkably, such a principle for heat and entropy power can be explicitly linked
to the rate of creation of correlations among the elements of the multipartite
system and, in turn, the non-Markovian nature of their reduced evolution. Such
features are illustrated in two exemplary cases.
PMID- 26430975
TI - Nonclassicality of Temporal Correlations.
AB - The results of spacelike separated measurements are independent of distant
measurement settings, a property one might call two-way no-signaling. In
contrast, timelike separated measurements are only one-way no-signaling since the
past is independent of the future but not vice versa. For this reason some
temporal correlations that are formally identical to nonclassical spatial
correlations can still be modeled classically. We propose a new formulation of
Bell's theorem for temporal correlations; namely, we define nonclassical temporal
correlations as the ones which cannot be simulated by propagating in time the
classical information content of a quantum system given by the Holevo bound. We
first show that temporal correlations between results of any projective quantum
measurements on a qubit can be simulated classically. Then we present a sequence
of general measurements on a single m-level quantum system that cannot be
explained by propagating in time an m-level classical system and using classical
computers with unlimited memory.
PMID- 26430976
TI - Quasilocal Conserved Operators in the Isotropic Heisenberg Spin-1/2 Chain.
AB - Composing higher auxiliary-spin transfer matrices and their derivatives, we
construct a family of quasilocal conserved operators of isotropic Heisenberg spin
1/2 chain and rigorously establish their linear independence from the well-known
set of local conserved charges.
PMID- 26430977
TI - Universality at Breakdown of Quantum Transport on Complex Networks.
AB - We consider single-particle quantum transport on parametrized complex networks.
Based on general arguments regarding the spectrum of the corresponding
Hamiltonian, we derive bounds for a measure of the global transport efficiency
defined by the time-averaged return probability. For treelike networks, we show
analytically that a transition from efficient to inefficient transport occurs
depending on the (average) functionality of the nodes of the network. In the
infinite system size limit, this transition can be characterized by an exponent
which is universal for all treelike networks. Our findings are corroborated by
analytic results for specific deterministic networks, dendrimers and Vicsek
fractals, and by Monte Carlo simulations of iteratively built scale-free trees.
PMID- 26430978
TI - High-Energy Cosmic Ray Self-Confinement Close to Extra-Galactic Sources.
AB - The ultrahigh-energy cosmic rays observed on the Earth are most likely
accelerated in extra-Galactic sources. For the typical luminosities invoked for
such sources, the electric current associated to the flux of cosmic rays that
leave them is large. The associated plasma instabilities create magnetic
fluctuations that can efficiently scatter particles. We argue that this
phenomenon forces cosmic rays to be self-confined in the source proximity for
energies Enu_{tau} oscillations in
appearance mode, i.e., by detecting the tau leptons produced in charged current
nu_{tau} interactions. The experiment took data from 2008 to 2012 in the CERN
Neutrinos to Gran Sasso beam. The observation of the nu_{MU}->nu_{tau}
appearance, achieved with four candidate events in a subsample of the data, was
previously reported. In this Letter, a fifth nu_{tau} candidate event, found in
an enlarged data sample, is described. Together with a further reduction of the
expected background, the candidate events detected so far allow us to assess the
discovery of nu_{MU}->nu_{tau} oscillations in appearance mode with a
significance larger than 5sigma.
PMID- 26430992
TI - Joint Measurements of Terahertz Wave Generation and High-Harmonic Generation from
Aligned Nitrogen Molecules Reveal Angle-Resolved Molecular Structures.
AB - We report the synchronized measurements of terahertz wave generation and high
harmonic generation from aligned nitrogen molecules in dual-color laser fields.
Both yields are found to be alignment dependent, showing the importance of
molecular structures in the generation processes. By calibrating the angular
ionization rates with the terahertz yields, we present a new way of retrieving
the angular differential photoionization cross section (PICS) from the harmonic
signals which avoids specific model calculations or separate measurements of the
alignment-dependent ionization rates. The measured PICS is found to be consistent
with theoretical predications, although some discrepancies exist. This all
optical method provides a new alternative for investigating molecular structures.
PMID- 26430987
TI - Search for Nucleon and Dinucleon Decays with an Invisible Particle and a Charged
Lepton in the Final State at the Super-Kamiokande Experiment.
AB - Search results for nucleon decays p->e^{+}X, p->MU^{+}X, n->nugamma (where X is
an invisible, massless particle) as well as dinucleon decays np->e^{+}nu, np
>MU^{+}nu, and np->tau^{+}nu in the Super-Kamiokande experiment are presented.
Using single-ring data from an exposure of 273.4 kton.yr, a search for these
decays yields a result consistent with no signal. Accordingly, lower limits on
the partial lifetimes of tau_{p->e^{+}X}>7.9*10^{32} yr, tau_{p
>MU^{+}X}>4.1*10^{32} yr, tau_{n->nugamma}>5.5*10^{32} yr, tau_{np
>e^{+}nu}>2.6*10^{32} yr, tau_{np->MU^{+}nu}>2.2*10^{32} yr, and tau_{np
>tau^{+}nu}>2.9*10^{31} yr at a 90% confidence level are obtained. Some of these
searches are novel.
PMID- 26430994
TI - Coulomb Bound States of Strongly Interacting Photons.
AB - We show that two photons coupled to Rydberg states via electromagnetically
induced transparency can interact via an effective Coulomb potential. This
interaction gives rise to a continuum of two-body bound states. Within the
continuum, metastable bound states are distinguished in analogy with quasibound
states tunneling through a potential barrier. We find multiple branches of
metastable bound states whose energy spectrum is governed by the Coulomb
potential, thus obtaining a photonic analogue of the hydrogen atom. Under certain
conditions, the wave function resembles that of a diatomic molecule in which the
two polaritons are separated by a finite "bond length." These states propagate
with a negative group velocity in the medium, allowing for a simple preparation
and detection scheme, before they slowly decay to pairs of bound Rydberg atoms.
PMID- 26430993
TI - Light-Dressing Effect in Laser-Assisted Elastic Electron Scattering by Xe.
AB - The light-dressing effect in Xe atoms was identified in laser-assisted elastic
electron scattering (LAES) signals. In the angular distribution of LAES signals
with energy shifts of +/-homega recorded by the scattering of 1 keV electrons by
Xe in an intense nonresonant laser field, a peak profile appeared at small
scattering angles (<0.5 degrees ). This peak was interpreted as evidence of the
light dressing of Xe atoms induced by an intense laser field on the basis of a
numerical simulation in which the light-dressing effect is included.
PMID- 26430995
TI - Wake-Driven Dynamics of Finite-Sized Buoyant Spheres in Turbulence.
AB - Particles suspended in turbulent flows are affected by the turbulence and at the
same time act back on the flow. The resulting coupling can give rise to rich
variability in their dynamics. Here we report experimental results from an
investigation of finite-sized buoyant spheres in turbulence. We find that even a
marginal reduction in the particle's density from that of the fluid can result in
strong modification of its dynamics. In contrast to classical spatial filtering
arguments and predictions of particle models, we find that the particle
acceleration variance increases with size. We trace this reversed trend back to
the growing contribution from wake-induced forces, unaccounted for in current
particle models in turbulence. Our findings highlight the need for improved
multiphysics based models that account for particle wake effects for a faithful
representation of buoyant-sphere dynamics in turbulence.
PMID- 26430996
TI - Absolute Instability near the Band Edge of Traveling-Wave Amplifiers.
AB - Applying the Briggs-Bers "pole-pinch" criterion to the exact transcendental
dispersion relation of a dielectric traveling wave tube (TWT), we find that there
is no absolute instability regardless of the beam current. We extend this
analysis to the circuit band edges of a linear beam TWT by approximating the
circuit mode as a hyperbola in the frequency-wave-number (omega-k) plane and
consider the weak coupling limit. For an operating mode whose group velocity is
in the same direction as the beam mode, we find that the lower band edge is not
subjected to absolute instability. At the upper band edge, we find a threshold
beam current beyond which absolute instability is excited. The nonexistence of
absolute instability in a linear beam TWT and the existence in a gyrotron TWT,
both at the lower band edge, is contrasted. The general study given here is
applicable to some contemporary TWTs such as metamaterial-based and advanced
Smith-Purcell TWTs.
PMID- 26430997
TI - Quasiperpendicular High Mach Number Shocks.
AB - Shock waves exist throughout the Universe and are fundamental to understanding
the nature of collisionless plasmas. Reformation is a process, driven by
microphysics, which typically occurs at high Mach number supercritical shocks.
While ongoing studies have investigated this process extensively both
theoretically and via simulations, their observations remain few and far between.
In this Letter we present a study of very high Mach number shocks in a parameter
space that has been poorly explored and we identify reformation using in situ
magnetic field observations from the Cassini spacecraft at 10 AU. This has given
us an insight into quasiperpendicular shocks across 2 orders of magnitude in
Alfven Mach number (M_{A}) which could potentially bridge the gap between modest
terrestrial shocks and more exotic astrophysical shocks. For the first time, we
show evidence for cyclic reformation controlled by specular ion reflection
occurring at the predicted time scale of ~0.3tau_{c}, where tau_{c} is the ion
gyroperiod. In addition, we experimentally reveal the relationship between
reformation and M_{A} and focus on the magnetic structure of such shocks to
further show that for the same M_{A}, a reforming shock exhibits stronger
magnetic field amplification than a shock that is not reforming.
PMID- 26430998
TI - Spatial Patterns in Rydberg Excitations from Logarithmic Pair Interactions.
AB - The collective excitations in ensembles of dissipative, laser driven ultracold
atoms exhibit crystal-like patterns, a many-body effect of the Rydberg blockade
mechanism. These crystalline structures are revealed in an experiment from a
postselection of configurations with fixed numbers of excitations. Here, we show
that these subensembles can be well represented by ensembles of effective
particles that interact via logarithmic pair potentials. This allows one to study
the emergent patterns with a small number of effective particles to determine the
phases of Rydberg crystals and to systematically study contributions from N-body
terms.
PMID- 26430999
TI - Impurity in a Bose-Einstein Condensate and the Efimov Effect.
AB - We investigate the zero-temperature properties of an impurity particle
interacting with a Bose-Einstein condensate (BEC), using a variational wave
function that includes up to two Bogoliubov excitations of the BEC. This allows
one to capture three-body Efimov physics, as well as to recover the first
nontrivial terms in the weak-coupling expansion. We show that the energy and
quasiparticle residue of the dressed impurity (polaron) are significantly lowered
by three-body correlations, even for weak interactions where there is no Efimov
trimer state in a vacuum. For increasing attraction between the impurity and the
BEC, we observe a smooth crossover from atom to Efimov trimer, with a
superposition of states near the Efimov resonance. We furthermore demonstrate
that three-body loss does not prohibit the experimental observation of these
effects. Our results thus suggest a route to realizing Efimov physics in a stable
quantum many-body system for the first time.
PMID- 26431000
TI - Electromagnetic Saturation of Angstrom-Sized Quantum Barriers at Terahertz
Frequencies.
AB - Metal-graphene-metal hybrid structures allow angstrom-scale van der Waals gaps,
across which electron tunneling occurs. We squeeze terahertz electromagnetic
waves through these lambda/10 000 000 gaps, accompanied by giant field
enhancements. Unprecedented transmission reduction of 97% is achieved with the
transient voltage across the gap saturating at 5 V. Electron tunneling
facilitated by the transient electric field strongly modifies the gap index,
starting a self-limiting process related to the barrier height. Our work enables
greater interplay between classical optics and quantum tunneling, and provides
optical indices to the van der Waals gaps.
PMID- 26431001
TI - Fractional Chern Insulators in Harper-Hofstadter Bands with Higher Chern Number.
AB - The Harper-Hofstadter model provides a fractal spectrum containing topological
bands of any integer Chern number C. We study the many-body physics that is
realized by interacting particles occupying Harper-Hofstadter bands with |C|>1.
We formulate the predictions of Chern-Simons or composite fermion theory in terms
of the filling factor nu, defined as the ratio of particle density to the number
of single-particle states per unit area. We show that this theory predicts a
series of fractional quantum Hall states with filling factors nu=r/(r|C|+1) for
bosons, or nu=r/(2r|C|+1) for fermions. This series includes a bosonic integer
quantum Hall state in |C|=2 bands. We construct specific cases where a single
band of the Harper-Hofstadter model is occupied. For these cases, we provide
numerical evidence that several states in this series are realized as
incompressible quantum liquids for bosons with contact interactions.
PMID- 26431002
TI - Observation of the Zero Hall Plateau in a Quantum Anomalous Hall Insulator.
AB - We report experimental investigations on the quantum phase transition between the
two opposite Hall plateaus of a quantum anomalous Hall insulator. We observe a
well-defined plateau with zero Hall conductivity over a range of magnetic field
around coercivity when the magnetization reverses. The features of the zero Hall
plateau are shown to be closely related to that of the quantum anomalous Hall
effect, but its temperature evolution exhibits a significant difference from the
network model for a conventional quantum Hall plateau transition. We propose that
the chiral edge states residing at the magnetic domain boundaries, which are
unique to a quantum anomalous Hall insulator, are responsible for the novel
features of the zero Hall plateau.
PMID- 26431003
TI - Electrical Tuning of Exciton Binding Energies in Monolayer WS_{2}.
AB - We demonstrate continuous tuning of the exciton binding energy in monolayer
WS_{2} by means of an externally applied voltage in a field-effect transistor
device. Using optical spectroscopy, we monitor the ground and excited excitonic
states as a function of gate voltage and track the evolution of the quasiparticle
band gap. The observed decrease of the exciton binding energy over the range of
about 100 meV, accompanied by the renormalization of the quasiparticle band gap,
is associated with screening of the Coulomb interaction by the electrically
injected free charge carriers at densities up to 8*10^{12} cm^{-2}. Complete
ionization of the excitons due to the electrical doping is estimated to occur at
a carrier density of several 10^{13} cm^{-2}.
PMID- 26431004
TI - Dirac Semimetals in Two Dimensions.
AB - Graphene is famous for being a host of 2D Dirac fermions. However, spin-orbit
coupling introduces a small gap, so that graphene is formally a quantum spin Hall
insulator. Here we present symmetry-protected 2D Dirac semimetals, which feature
Dirac cones at high-symmetry points that are not gapped by spin-orbit
interactions and exhibit behavior distinct from both graphene and 3D Dirac
semimetals. Using a two-site tight-binding model, we construct representatives of
three possible distinct Dirac semimetal phases and show that single symmetry
protected Dirac points are impossible in two dimensions. An essential role is
played by the presence of nonsymmorphic space group symmetries. We argue that
these symmetries tune the system to the boundary between a 2D topological and
trivial insulator. By breaking the symmetries we are able to access trivial and
topological insulators as well as Weyl semimetal phases.
PMID- 26431005
TI - Charge Number Dependence of the Dephasing Rates of a Graphene Double Quantum Dot
in a Circuit QED Architecture.
AB - We use an on-chip superconducting resonator as a sensitive meter to probe the
properties of graphene double quantum dots at microwave frequencies.
Specifically, we investigate the charge dephasing rates in a circuit quantum
electrodynamics architecture. The dephasing rates strongly depend on the number
of charges in the dots, and the variation has a period of four charges, over an
extended range of charge numbers. Although the exact mechanism of this fourfold
periodicity in dephasing rates is an open problem, our observations hint at the
fourfold degeneracy expected in graphene from its spin and valley degrees of
freedom.
PMID- 26431006
TI - Fractional Quantum Hall States at nu=13/5 and 12/5 and Their Non-Abelian Nature.
AB - Topological quantum states with non-Abelian Fibonacci anyonic excitations are
widely sought after for the exotic fundamental physics they would exhibit, and
for universal quantum computing applications. The fractional quantum Hall (FQH)
state at a filling factor of nu=12/5 is a promising candidate; however, its
precise nature is still under debate and no consensus has been achieved so far.
Here, we investigate the nature of the FQH nu=13/5 state and its particle-hole
conjugate state at 12/5 with the Coulomb interaction, and we address the issue of
possible competing states. Based on a large-scale density-matrix renormalization
group calculation in spherical geometry, we present evidence that the essential
physics of the Coulomb ground state (GS) at nu=13/5 and 12/5 is captured by the
k=3 parafermion Read-Rezayi state (RR_{3}), including a robust excitation gap and
the topological fingerprint from the entanglement spectrum and topological
entanglement entropy. Furthermore, by considering the infinite-cylinder geometry
(topologically equivalent to torus geometry), we expose the non-Abelian GS sector
corresponding to a Fibonacci anyonic quasiparticle, which serves as a signature
of the RR_{3} state at 13/5 and 12/5 filling numbers.
PMID- 26431007
TI - Alloy Engineering of Defect Properties in Semiconductors: Suppression of Deep
Levels in Transition-Metal Dichalcogenides.
AB - Developing practical approaches to effectively reduce the amount of deep defect
levels in semiconductors is critical for their use in electronic and
optoelectronic devices, but this still remains a very challenging task. In this
Letter, we propose that specific alloying can provide an effective means to
suppress the deep defect levels in semiconductors while maintaining their basic
electronic properties. Specifically, we demonstrate that for transition-metal
dichalcogenides, such as MoSe_{2} and WSe_{2}, where anion vacancies are the most
abundant defects that can induce deep levels, the deep levels can be effectively
suppressed in Mo_{1-x}W_{x}Se_{2} alloys at low W concentrations. This surprising
phenomenon is associated with the fact that the band edge energies can be
substantially tuned by the global alloy concentration, whereas the defect level
is controlled locally by the preferred locations of Se vacancies around W atoms.
Our findings illustrate a concept of alloy engineering and provide a promising
approach to control the defect properties of semiconductors.
PMID- 26431008
TI - Enhanced Bulk-Edge Coulomb Coupling in Fractional Fabry-Perot Interferometers.
AB - Recent experiments use Fabry-Perot (FP) interferometry to claim that the nu=5/2
quantum Hall state exhibits non-Abelian topological order. We note that the
experiments appear inconsistent with a model neglecting bulk-edge Coulomb
coupling and Majorana tunneling, so we reexamine the theory of FP devices. Even a
moderate Coulomb coupling may strongly affect some fractional plateaus, but very
weakly affect others, allowing us to model the data over a wide range of
plateaus. While experiments are consistent with the nu=5/2 state harboring Moore
Read topological order, they may have measured Coulomb effects rather than an
"even-odd effect" due to non-Abelian braiding.
PMID- 26430984
TI - First Observation of CP Violation in B[over -]^{0}->D_{CP}^{(*)}h^{0} Decays by a
Combined Time-Dependent Analysis of BABAR and Belle Data.
AB - We report a measurement of the time-dependent CP asymmetry of B[over -]^{0}
>D_{CP}^{(*)}h^{0} decays, where the light neutral hadron h^{0} is a pi^{0}, eta,
or omega meson, and the neutral D meson is reconstructed in the CP eigenstates
K^{+}K^{-}, K_{S}^{0}pi^{0}, or K_{S}^{0}omega. The measurement is performed
combining the final data samples collected at the Upsilon(4S) resonance by the
BABAR and Belle experiments at the asymmetric-energy B factories PEP-II at SLAC
and KEKB at KEK, respectively. The data samples contain (471+/-3)*10^{6} BB[over
] pairs recorded by the BABAR detector and (772+/-11)*10^{6} BB[over -] pairs
recorded by the Belle detector. We measure the CP asymmetry parameters
eta_{f}S=+0.66+/-0.10(stat)+/-0.06(syst) and C=-0.02+/-0.07(stat)+/-0.03(syst).
These results correspond to the first observation of CP violation in B[over
]^{0}->D_{CP}^{(*)}h^{0} decays. The hypothesis of no mixing-induced CP violation
is excluded in these decays at the level of 5.4 standard deviations.
PMID- 26431009
TI - Semiconductor-Nanowire-Based Superconducting Qubit.
AB - We introduce a hybrid qubit based on a semiconductor nanowire with an epitaxially
grown superconductor layer. Josephson energy of the transmonlike device
("gatemon") is controlled by an electrostatic gate that depletes carriers in a
semiconducting weak link region. Strong coupling to an on-chip microwave cavity
and coherent qubit control via gate voltage pulses is demonstrated, yielding
reasonably long relaxation times (~0.8 MUs) and dephasing times (~1 MUs),
exceeding gate operation times by 2 orders of magnitude, in these first
generation devices. Because qubit control relies on voltages rather than fluxes,
dissipation in resistive control lines is reduced, screening reduces cross talk,
and the absence of flux control allows operation in a magnetic field, relevant
for topological quantum information.
PMID- 26431010
TI - Realization of Microwave Quantum Circuits Using Hybrid Superconducting
Semiconducting Nanowire Josephson Elements.
AB - We report the realization of quantum microwave circuits using hybrid
superconductor-semiconductor Josephson elements comprised of InAs nanowires
contacted by NbTiN. Capacitively shunted single elements behave as transmon
circuits with electrically tunable transition frequencies. Two-element circuits
also exhibit transmonlike behavior near zero applied flux but behave as flux
qubits at half the flux quantum, where nonsinusoidal current-phase relations in
the elements produce a double-well Josephson potential. These hybrid Josephson
elements are promising for applications requiring microwave superconducting
circuits operating in a magnetic field.
PMID- 26431011
TI - Bound States of a Ferromagnetic Wire in a Superconductor.
AB - We consider the problem of bound states in strongly anisotropic ferromagnetic
impurities in a superconductor, motivated by recent experiments that claim to
observe Majorana modes at the ends of ferromagnetic wires on a superconducting
substrate [S. Nadj-Perge et al., Science 346, 602 (2014)]. Generalizing the
successful theory of bound states of spherically symmetric impurities, we
consider a wirelike potential using both analytical and numerical approaches. We
find that away from the ends of the wire the bound states form bands with
pronounced van Hove singularities, giving rise to subgap peaks in the local
density of states. For sufficiently strong magnetization of the wire, we show
that this process generically produces a sharp peak at zero energy in the local
density of states near the ends of the wire. This zero-energy peak has
qualitative similarities to the claimed signature of a Majorana mode observed in
the aforementioned experiment.
PMID- 26431012
TI - Charge-Induced Spin Torque in Anomalous Hall Ferromagnets.
AB - We demonstrate that spin-orbit coupled electrons in a magnetically doped system
exert a spin torque on the local magnetization, without a flowing current, when
the chemical potential is modulated in a magnetic field. The spin torque is
proportional to the anomalous Hall conductivity, and its effective field strength
may overcome the Zeeman field. Using this effect, the direction of the local
magnetization is switched by gate control in a thin film. This charge-induced
spin torque is essentially an equilibrium effect, in contrast to the conventional
current-induced spin-orbit torque, and, thus, devices using this operating
principle possibly have higher efficiency than the conventional ones. In addition
to a comprehensive phenomenological derivation, we present a physical
understanding based on a model of a Dirac-Weyl semimetal, possibly realized in a
magnetically doped topological insulator. The effect might be realized also in
nanoscale transition materials, complex oxide ferromagnets, and dilute magnetic
semiconductors.
PMID- 26431013
TI - Spin Fluctuations from Hertz to Terahertz on a Triangular Lattice.
AB - The temporal magnetic correlations of the triangular-lattice antiferromagnet
NiGa_{2}S_{4} are examined through 13 decades (10^{-13}-1 sec) using ultrahigh
resolution inelastic neutron scattering, muon spin relaxation, and ac and
nonlinear susceptibility measurements. Unlike the short-ranged spatial
correlations, the temperature dependence of the temporal correlations show
distinct anomalies. The spin fluctuation rate decreases precipitously upon
cooling towards T^{*}=8.5 K, but fluctuations on the microsecond time scale then
persist in an anomalous dynamical regime for 4 K24 h with 50% of drug release. The in vivo results indicated that
transferrin-targeted TPGS micelles could be a promising carrier for brain
targeting due to nano-sized drug delivery, solubility enhancement and
permeability which provided an improved and prolonged brain targeting of DTX in
comparison to the non-targeted micelles and marketed formulation.
PMID- 26431066
TI - The relationship between autoimmunity and specific immunotherapy for allergic
diseases.
AB - The aim of this study was to perform a 20-year post-specific immunotherapy (SIT)
observational evaluation for an assessment of any manifestations of autoimmune
disease or the appearance of autoantibodies in serum. In total, 1,888 patients
(902 women and 986 men) were observed. The mean age of the patients was 34.1 +/-
12.4 y at the start of the prospective observation after finishing SIT. New
incidences of autoimmune disease and/or the presence of autoantibodies in serum
were monitored. The SIT group was compared with control groups consisting of
allergic patients who had very received SIT and with non-allergic subjects. There
were no significant differences in the autoimmune disease prevalence between the
allergic patients with or without SIT. However, significantly higher prevalence
of 4 different autoimmune diseases (AID) were observed in the non-allergic
patients during the same period. Additionally, the incidence of 8 different
autoantibodies was significantly higher in non-allergic patients than in control
subjects. Hashimoto disease was the most common autoimmune disease observed. The
results of this long-term observational study indicated a lack of a significant
prevalence of new instances of autoimmune disease during 20 y of observation post
SIT and at a rate lower than that of non-allergic control subjects, suggesting
that SIT is safe in this regard in the long term.
PMID- 26431065
TI - Lactoferrin Expression in Human and Murine Ocular Tissue.
AB - PURPOSE: Lactoferrin (LF) is a multifunctional protein known to provide innate
defense due to its antimicrobial and anti-inflammatory properties. In the eye, LF
has been identified in the tears and vitreous humor. Its presence in other ocular
tissues has not been determined. Our aim is to assess the presence of LF in the
cornea, iris, retina and retinal pigment epithelium (RPE) of humans and mice.
METHODS: To test for the endogenous production of LF, reverse transcription
polymerase chain reaction was performed in cultured human cells from the cornea
and RPE and in murine tissues. To confirm LF localization in specific ocular
tissue, immunohistochemistry was performed on flat mounts of cornea, retina and
RPE in human donor eyes. The presence of LF was assessed by western blotting in
human and mouse ocular tissue and human culture cells (cornea and RPE). To verify
antibody specificity, purified human LF and transferrin (TF) were used on 1D and
2D western blots. RESULTS: LF gene expression was confirmed in the cornea and RPE
cell cultures from humans, suggesting that LF is an endogenously produced
protein. PCR results from mouse ocular tissue showed LF expression in cornea,
iris, RPE, but not in retina. These results were also consistent with
immunohistochemical localization of LF in human donor tissue. Antibody reaction
for human LF was specific and western blotting showed its presence in the cornea,
iris and RPE tissues. A faint reaction for the retina was observed but was likely
due to contamination from other ocular tissues. Multiple commercially available
antibodies for murine LF cross-reacted with TF, so no reliable results were
obtained for murine western blot. CONCLUSION: LF is expressed in multiple eye
tissues of humans and mice. This widespread expression and multifunctional
activity of LF suggests that it may play an important role in protecting eye
tissues from inflammation-associated diseases.
PMID- 26431067
TI - Ochratoxin A in artisan salami produced in Veneto (Italy).
AB - Fifty samples of artisan salami purchased in Veneto (Italy) were analysed for the
determination of ochratoxin A (OTA). The analytical method, based on a sample
preparation procedure with immunoaffinity columns (IACs), together with analysis
by high-performance liquid chromatography with fluorescence detection (HPLC-FD),
has guaranteed a high rate of recovery (about 97%), limit of detection (LOD) and
limit of quantification (LOQ), respectively, of 0.06 ug kg(-1) and 0.20 ug kg(
1). OTA was detected in five samples, but only one exceeded the guideline value
(1 ug kg(-1)) established by the Italian Ministry of Health for pork meat and
derived products. The results would seem to suggest that salami made with the
traditional, non-industrial production method can be considered safe as regards
contamination by OTA. However, the very high concentration observed in one sample
proves that a high OTA contamination is also possible in this type of product.
Thus, the controls of mycotoxin contamination must consider also salami.
PMID- 26431068
TI - An unusual case of schwannomatosis with bilateral maxillary sinus schwannomas and
a novel SMARCB1 gene mutation.
AB - Schwannomas are benign tumors that arise from Schwann cells in the peripheral
nervous system. Patients with multiple schwannomas without signs and symptoms of
neurofibromatosis Type 1 or 2 have the rare disease schwannomatosis. Tumors in
these patients occur along peripheral nerves throughout the body. Mutations of
the SMARCB1 gene have been described as one of the predisposing genetic factors
in the development of this disease. This report describes a patient who was
observed for 6 years after having undergone removal of 7 schwannomas, including
bilateral maxillary sinus schwannomas, a tumor that has not been previously
reported. Genetic analysis revealed a novel mutation of c.93G>A in exon 1 of the
SMARCB1 gene.
PMID- 26431069
TI - Induction of proinflammatory cytokine production in intervertebral disc cells by
macrophage-like THP-1 cells requires mitogen-activated protein kinase activity.
AB - OBJECTIVE: To determine the role played by mitogen-activated protein kinase
(MAPK) signaling in the interactions between macrophages and intervertebral disc
(IVD) cells, it was hypothesized that MAPK inhibition would modulate the
production of the proinflammatory cytokines associated with inflammatory reaction
in IVD cells. METHODS: Human annulus fibrosus (AF) and nucleus pulposus (NP)
cells were cocultured with phorbol myristate acetate-stimulated macrophage-like
THP-1 cells, with and without SB202190 (a p38-alpha and -beta inhibitor),
SP600125 (a c-Jun N-terminal kinase [JNK] inhibitor), and PD98059 (an
extracellular signal-regulated kinase [ERK] 1/2 inhibitor). The cytokines in
conditioned media from cocultured and macrophage-exposed (nemotic) cells were
assayed using enzyme-linked immunosorbent assays (ELISAs). RESULTS: Interleukin
(IL)-6 and IL-8 were secreted in greater quantities by the cocultured cells
compared with naive IVD cells and macrophages (MPhi) cultured alone. The tumor
necrosis factor (TNF)- alpha and IL-6 levels produced by the NP cells cocultured
with MPhis (NP-MPhi) were significantly lower than those produced by AF cells
cocultured with MPhis (AF-MPhi). SB202190 dose-dependently suppressed IL-6
secretion by AF-MPhi and NP-MPhi cocultures, and 10 MUM SB202190 significantly
decreased IL-6 and IL-8 production in nemotic AF and NP pellets. SP600125 at 10
MUM significantly suppressed the production of TNF alpha IL-6. and IL-8 in AF
MPhi and NP-MPhi cocultures and significantly suppressed IL-1beta production in
the NP-MPhi coculture. Administration of 10 MUM PD98059 significantly decreased
IL-6 levels in the AF-MPhi coculture, and decreased the levels of TNF alpha and
IL-8 in both the AF-MPhi and NP-MPhi cocultures. CONCLUSIONS: The present study
shows that inhibitors of p38 MAPK effectively controlled IL-6 production during
inflammatory reactions and that JNK and ERK1/2 inhibitors successfully suppressed
the production of major proinflammatory cytokines during interactions between
macrophages and IVD cells. Therefore, selective blockade of these signals may
serve as a therapeutic approach to symptomatic IVD degeneration.
PMID- 26431070
TI - Correlation between cervical spine sagittal alignment and clinical outcome after
cervical laminoplasty for ossification of the posterior longitudinal ligament.
AB - OBJECTIVE: The goal of this study was to determine the relationship between
cervical spine sagittal alignment and clinical outcomes after cervical
laminoplasty in patients with ossification of the posterior longitudinal ligament
(OPLL). METHODS: Fifty consecutive patients who underwent a cervical laminoplasty
for OPLL between January 2012 and January 2013 and who were followed up for at
least 1 year were analyzed in this study. Standing plain radiographs of the
cervical spine, CT (midsagittal view), and MRI (T2-weighted sagittal view) were
obtained (anteroposterior, lateral, flexion, and extension) pre- and
postoperatively. Cervical spine alignment was assessed with the following 3
parameters: the C2-7 Cobb angle, C2-7 sagittal vertical axis (SVA), and T-1 slope
minus C2-7 Cobb angle. The change in cervical sagittal alignment was defined as
the difference between the post- and preoperative C2-7 Cobb angles, C2-7 SVAs,
and T-1 slope minus C2-7 Cobb angles. Outcome assessments (visual analog scale
[VAS], Oswestry Neck Disability Index [NDI], 36-Item Short-Form Health Survey [SF
36], and Japanese Orthopaedic Association [JOA] scores) were obtained in all
patients pre- and postoperatively. RESULTS: The average patient age was 56.3
years (range 38-72 years). There were 34 male patients and 16 female patients.
Cervical laminoplasty for OPLL helped alleviate radiculomyelopathy. Compared with
the preoperative scores, improvement was seen in postoperative VAS and JOA
scores. After laminoplasty, 35 patients had kyphotic changes, and 15 had lordotic
changes. However, cervical sagittal alignment after laminoplasty was not
significantly associated with clinical outcomes in terms of postoperative
improvement of the JOA score (C2-7 Cobb angle: p = 0.633; C2-7 SVA: p = 0.817; T
1 slope minus C2-7 lordosis: p = 0.554), the SF-36 score (C2-7 Cobb angle: p =
0.554; C2-7 SVA: p = 0.793; T-1 slope minus C2-7 lordosis: p = 0.829), the VAS
neck score (C2-7 Cobb angle: p = 0.263; C2-7 SVA: p = 0.716; T-1 slope minus C2-7
lordosis: p = 0.497), or the NDI score (C2-7 Cobb angle: p = 0.568; C2-7 SVA: p =
0.279; T-1 slope minus C2-7 lordosis: p = 0.966). Similarly, the change in
cervical sagittal alignment was not related to the JOA (p = 0.604), SF-36 (p =
0.308), VAS neck (p = 0.832), or NDI (p = 0.608) scores. CONCLUSIONS: Cervical
laminoplasty for OPLL improved radiculomyelopathy. Cervical laminoplasty
increased the probability of cervical kyphotic alignment. However, cervical
sagittal alignment and clinical outcomes were not clearly related.
PMID- 26431071
TI - How do spinal schwannomas progress? The natural progression of spinal schwannomas
on MRI.
AB - OBJECTIVE: Little is known about the progression of spinal schwannomas. The aim
of this study was to determine the natural progression of spinal schwannomas and
establish the risk of tumor growth. METHODS: This study retrospectively analyzed
data from 23 patients (12 men and 11 women, 40-89 years old) with schwannomas
detected by MRI. The mean follow-up period was 5 years (range 2-10 years). The
absolute and relative growth rates of the tumors were calculated. RESULTS: The
average tumor size was 1495 mm(3) at the initial visit and 2224 mm(3) at the
final follow-up. The average absolute growth rate was 139 mm(3) per year, and the
average relative growth rate was 5.3% per year. Tumors were classified into 3
groups based on enhancement patterns: isointense/hyperintense (iso/high; 11
cases), rim enhancement when enhancement was peripheral (high/rim; 5 cases), and
heterogeneous/heterogeneous (hetero/hetero; 7 cases) based on Gd-enhanced T2
weighted MRI. The average absolute growth rates of the 3 lesion groups were 588
mm(3), 957 mm(3), and 3379 mm(3), respectively (p < 0.01). CONCLUSIONS: Although
the tumors classified as iso/high and high/rim on T2-weighted Gd-enhanced MR
images were small and grew very little, most tumors with hetero/hetero
classification increased in size. Hetero/hetero-type tumors should be followed
closely and may require surgery.
PMID- 26431072
TI - Anterior corpectomy via the mini-open, extreme lateral, transpsoas approach
combined with short-segment posterior fixation for single-level traumatic lumbar
burst fractures: analysis of health-related quality of life outcomes and patient
satisfaction.
AB - OBJECTIVE: The authors present clinical outcome data and satisfaction of patients
who underwent minimally invasive vertebral body corpectomy and cage placement via
a mini-open, extreme lateral, transpsoas approach and posterior short-segment
instrumentation for lumbar burst fractures. METHODS: Patients with unstable
lumbar burst fractures who underwent corpectomy and anterior column
reconstruction via a mini-open, extreme lateral, transpsoas approach with short
segment posterior fixation were reviewed retrospectively. Demographic
information, operative parameters, perioperative radiographic measurements, and
complications were analyzed. Patient-reported outcome instruments (Oswestry
Disability Index [ODI], 12-Item Short Form Health Survey [SF-12]) and an anterior
scar-specific patient satisfaction questionnaire were recorded at the latest
follow-up. RESULTS: Twelve patients (7 men, 5 women, average age 42 years, range
22-68 years) met the inclusion criteria. Lumbar corpectomies with anterior column
support were performed (L-1, n = 8; L-2, n = 2; L-3, n = 2) and supplemented with
short-segment posterior instrumentation (4 open, 8 percutaneous). Four patients
had preoperative neurological deficits, all of which improved after surgery. No
new neurological complications were noted. The anterior incision on average was
6.4 cm (range 5-8 cm) in length, caused mild pain and disability, and was
aesthetically acceptable to the large majority of patients. Three patients
required chest tube placement for pleural violation, and 1 patient required
reoperation for cage subsidence/hardware failure. Average clinical follow-up was
38 months (range 16-68 months), and average radiographic follow-up was 37 months
(range 6-68 months). Preoperative lumbar lordosis and focal lordosis were
significantly improved/maintained after surgery. Patients were satisfied with
their outcomes, had minimal/moderate disability (average ODI score 20, range 0
52), and had good physical (SF-12 physical component score 41.7% +/- 10.4%) and
mental health outcomes (SF-12 mental component score 50.2% +/- 11.6%) after
surgery. CONCLUSIONS: Anterior corpectomy and cage placement via a mini-open,
extreme lateral, transpsoas approach supplemented by short-segment posterior
instrumentation is a safe, effective alternative to conventional approaches in
the treatment of single-level unstable burst fractures and is associated with
excellent functional outcomes and patient satisfaction.
PMID- 26431073
TI - Building an electronic health record integrated quality of life outcomes registry
for spine surgery.
AB - OBJECTIVE: Demonstrating the value of spine care requires adequate outcomes
assessment. Long-term outcomes are best measured as overall improvement in
quality of life (QOL) after surgical intervention. Present registries often
require parallel data entry, introducing inefficiencies and limiting compliance.
The authors detail the methodology of constructing an integrated electronic
health record (EHR) system to collect QOL metrics and demonstrate the effect of
data collection on routine clinical workflow. A streamlined approach to
collecting QOL data can capture patient data without requiring dual data entry
and without increasing clinic visit times. METHODS: Through extensive literature
review, a combination of QOL assessments was selected, consisting of the Patient
Health Questionnaire-2 and -9, Oswestry Disability Index, Neck Disability Index,
and visual analog scale for pain. These metrics were used to provide assessment
of QOL following spine surgery and were incorporated into standard clinic
workflow by a multidisciplinary team of surgeons, advanced practice providers,
and health care information technology specialists. A clinical dashboard tracking
more than 25 patient variables was developed. Clinic flow was assessed and
opportunities for improvement reviewed. Duration of clinic visits before and
after initiation of QOL measure capture was recorded, with assessment of mean
clinic visit times for the 12 months before and the 12 months after
implementation. RESULTS: The integrated QOL capture was instituted for 3 spine
surgeons in a tertiary care academic center. In the 12-month period prior to
initiating collection of QOL data, 806 new patient visits were completed with an
average visit time of 127.9 +/- 51.5 minutes. In the 12 months after
implementation, 1013 new patient visits were recorded, with 791 providing QOL
measures with an average visit time of 117.0 +/- 45.7 minutes. Initially the
primary means of collecting patient outcome data was via paper form, with gradual
transition to collection via entry into the electronic medical records system. To
improve electronic data capture, paper forms were eliminated and an online portal
used as part of the patient rooming process. This improved electronic capture to
nearly 98% without decreasing the number of patients enrolled in the process.
CONCLUSIONS: A systematic approach to collecting spine-related QOL data within an
EHR system is feasible and offers distinct advantages over registries that
require dual data entry. The process of data collection does not impact patients'
clinical visit or providers' clinical workflow. This approach is scalable, and
may form the foundation for a decentralized outcomes registry network.
PMID- 26431074
TI - Are we ready to assess the value of treatment options in oncology?
PMID- 26431075
TI - Misfit stabilized embedded nanoparticles in metallic alloys.
AB - Nanoscale inhomogeneities are typical for numerous metallic alloys and crucially
important for their practical applications. At the same time, stabilization
mechanisms of such a state are poorly understood. We present a general overview
of the problem, together with a more detailed discussion of the prototype
example, namely, Guinier-Preston zones in Al-based alloys. It is shown that
coherent strain due to a misfit between inclusion and host crystal lattices plays
a decisive role in the emergence of the inhomogeneous state. We suggest a model
explaining the formation of ultrathin plates (with the thickness of a few lattice
constants) typical for Al-Cu alloys. Discreteness of the array of misfit
dislocations and long-ranged elastic interactions between them are the key
ingredients of the model. This opens a way for a general understanding of the
nature of (meta)stable embedded nanoparticles in practically important systems.
PMID- 26431076
TI - A Systematic Review of Financial Incentives for Physical Activity: The Effects on
Physical Activity and Related Outcomes.
AB - The aim of this review is to give an overview of the available evidence on the
effects of financial incentives to stimulate physical activity. Therefore, a
systematic literature search was performed for randomized trials that investigate
the effects of physical-activity-related financial incentives for individuals.
Twelve studies with unconditional incentives (eg, free membership sport facility)
and conditional incentives (ie, rewards for reaching physical-activity goals)
related to physical activity were selected. Selected outcomes were physical
activity, sedentary behavior, fitness, and weight. Results show that
unconditional incentives do not affect physical activity or the other selected
outcomes. For rewards, some positive effects were found and especially for
rewards provided for physical-activity behavior instead of attendance. In
conclusion, rewards seem to have positive effects on physical activity, while
unconditional incentives seem to have no effect. However, it should be kept in
mind that the long-term effects of financial incentives are still unclear.
PMID- 26431077
TI - Negotiating the equivocality of palliative care: a grounded theory of team
communicative processes in inpatient medicine.
AB - In the majority of U.S. hospitals, inpatient medicine teams make palliative care
decisions in the absence of a formalized palliative system. Using a grounded
theory approach, interviews with inpatient team members were systematically
analyzed to uncover how participants conceptualize palliative care and how they
regard the communicative structures that underlie its delivery. During analysis,
Weick's model of organizing emerged as a framework that fit the data. The 39
participant inpatient team members discussed palliative care as primarily a
communicative process. Themes describing the meaning of palliative care emerged
around the concepts of receiver of care, timeline of care, and location of care.
The emerging model included four stages in the communicative processes of
inpatient palliative care: (a) interpret the need, (b) initiate the conversation,
(c) integrate the processes, and (d) identify what works. In contrast to stable,
focused palliative care teams or hospice care teams, which have prescribed
patient populations and processes, the inpatient medicine team faces the
equivocality of providing palliative care within a broader practice. This
research offers a four-phase model to show how these inpatient teams communicate
within this context. Implications for the provision of palliative care are
discussed.
PMID- 26431078
TI - Determination of synergy between sulbactam, meropenem and colistin in carbapenem
resistant Klebsiella pneumoniae and Acinetobacter baumannii isolates and
correlation with the molecular mechanism of resistance.
AB - Treatment of infections with carbapenem-resistant Gram negative organism is a
major challenge especially among intensive care patients. Combinations of
sulbactam, meropenem and colistin was studied for its synergistic activity
against 100 invasive isolates of carbapenem-resistant Klebsiella pneumoniae and
Acinetobacter baumannii-calcoaceticus complex by checkerboard assay and time kill
assay (TKA). In addition, presence of carbapenemase production was determined by
multiplex PCR. Time kill assay detected more synergy than checkerboard assay.
Good bactericidal activity of 70-100% was noted with the combinations tested.
Among K. pneumoniae, isolates producing NDM carbapenemase alone showed
significantly more synergy than isolates producing OXA-48-like carbapenemases. In
treatment of infection with carbapenem-resistant organisms, the site of infection
and the carbapenemase produced may help determine the combination most likely to
clear the infection.
PMID- 26431079
TI - A Single-Component Conductor Based on a Radical Gold Dithiolene Complex with
Alkyl-Substituted Thiophene-2,3-dithiolate Ligand.
AB - Alkyl-substituted thiophene-2,3-dithiolate ligands are prepared through a Thio
Claisen rearrangement of 4,5-bis(propargylthio)-1,3-dithiole-2-thione
derivatives. The two novel dithiolate ligands, namely, 4,5-dimethyl-thiophene-2,3
dithiolate (alpha-Me2tpdt) and 4-ethyl-5-methyl-thiophene-2,3-dithiolate (alpha
EtMetpdt), are engaged in anionic Au(III) square planar complexes formulated as
[Au(alpha-Me2tpdt)2](-) and [Au(alpha-EtMetpdt)2](-), isolated as Ph4P(+) salts.
Monoelectronic oxidation gives the neutral radical complexes [Au(alpha
Me2tpdt)2](*) and [Au(alpha-EtMetpdt)2](*). The latter crystallizes into uniform
stacks with limited interstack interactions, giving rise to a calculated half
filled band structure. It exhibits a semiconducting behavior with room
temperature conductivity of 3 * 10(-3) S cm(-1), indicating that this single
component conductor can be described as a Mott insulator. The different
structures observed in [Au(alpha-EtMetpdt)2](*) and the known [Au(Et
thiazdt)2](*) complex (Et-thiazdt: N-ethyl-thiazoline-2-thione-4,5-dithiolate),
despite their very similar shapes, are tentatively attributed to differences in
the electronic structures of the ligand skeleton.
PMID- 26431089
TI - Role Of Vitamin D And Adipose Tissue Hormones In Women With Reproductive
Disorders.
AB - The role of vitamin D beyond that it plays in bone metabolism and calcium
homeostasis has been lately quite emphasized. In this respect, vitamin D
deficiency has been associated with higher risk of cardiovascular disease,
metabolic syndrome, and reproductive disorders. Growing evidence has suggested
that vitamin D deficiency is implicated in the pathogenesis of insulin resistance
and the development of metabolic disorders in the polycystic ovary syndrome. The
goal of the review is to present contemporary concepts of the relationship
between hormones affecting the metabolic body status, serum vitamin D levels and
the reproductive function.
PMID- 26431088
TI - Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic
Bile Acid Signaling.
AB - Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to
occur during cholestatic liver injury. Furthermore, we have demonstrated that in
a model of cholestasis, serum bile acids gain entry into the brain via a leaky
blood brain barrier and that hypothalamic bile acid content is increased.
Therefore, the aim of the current study was to determine the effects of bile acid
signaling on the HPA axis. The data presented show that HPA axis suppression
during cholestatic liver injury, specifically circulating corticosterone levels
and hypothalamic corticotropin releasing hormone (CRH) expression, can be
attenuated by administration of the bile acid sequestrant cholestyramine.
Secondly, treatment of hypothalamic neurons with various bile acids suppressed
CRH expression and secretion in vitro. However, in vivo HPA axis suppression was
only evident after the central injection of the bile acids taurocholic acid or
glycochenodeoxycholic acid but not the other bile acids studied. Furthermore, we
demonstrate that taurocholic acid and glycochenodeoxycholic acid are exerting
their effects on hypothalamic CRH expression after their uptake through the
apical sodium-dependent bile acid transporter and subsequent activation of the
glucocorticoid receptor. Taken together with previous studies, our data support
the hypothesis that during cholestatic liver injury, bile acids gain entry into
the brain, are transported into neurons through the apical sodium-dependent bile
acid transporter and can activate the glucocorticoid receptor to suppress the HPA
axis. These data also lend themselves to the broader hypothesis that bile acids
may act as central modulators of hypothalamic peptides that may be altered during
liver disease.
PMID- 26431090
TI - Strategies For Immobilization Of Bioactive Organic Molecules On Titanium Implant
Surfaces - A Review.
AB - Numerous approaches have been used to improve the tissue-implant interface of
titanium (Ti) and titanium alloy (Ti6Al4V). They all aim at increasing cell
migration and attachment to the metal, preventing unspecific protein adsorption
and improving post-implantation healing process. Promising methods for titanium
and titanium alloy surface modification are based on the immobilization of
biologically active organic molecules. New and interesting biochemical approaches
to such surface modification include layer-by-layer deposition of polyelectrolyte
films, phage display-selected surface binding peptides and self-assembled DNA
monolayer systems. The present review summarizes the scientific information about
these methods, which are at in vitro or in vivo development stages, and hopes to
promote their future application in dental implantology and in oral and
maxillofacial surgery.
PMID- 26431091
TI - Autism Spectrum Disorder - A Complex Genetic Disorder.
AB - Autism spectrum disorder is an entity that reflects a scientific consensus that
several previously separated disorders are actually a single spectrum disorder
with different levels of symptom severity in two core domains - deficits in
social communication and interaction, and restricted repetitive behaviors. Autism
spectrum disorder is diagnosed in all racial, ethnic and socioeconomic groups and
because of its increased prevalence, reported worldwide through the last years,
made it one of the most discussed child psychiatric disorders. In term of
aetiology as several other complex diseases, Autism spectrum disorder is
considered to have a strong genetic component.
PMID- 26431092
TI - Selection Of The Optimal Level Of Distal Fixation For Correction Of Scheuermann's
Hyperkyphosis.
AB - OBJECTIVE: To analyze the efficacy of the method for selecting the distal level
of fusion in treatment of thoracic hyperkyphosis in patients with Scheuermann's
disease. BACKGROUND: The fusion area needs to include all the kyphotic deformity
in Scheuermann patients; however, precise levels of the distal fixation have not
been determined yet. STUDY DESIGN: Retrospective cohort review. MATERIALS AND
METHODS: Thirty-six patients were operated in the Department of Children and
Adolescent Spine Pathology between 2007 and 2010. These patients were divided
into two groups: in group I (n = 29) a lower instrumented vertebra corresponded
to the sagittal stable one and in group II (n = 7) - this vertebra located
proximally. RESULTS: The mean preoperative kyphosis was 79.3 degrees +/- 11.6
degrees , the postoperative - 40.6 degrees +/- 11.9 degrees (correction of
49.9%), loss of correction was 4.9 degrees +/- 7.0 degrees . Sagittal balance
changed from -0.3 +/- 3.2 cm before surgery to -1.7 +/- 2.1 cm after surgery.
Distal junctional kyphosis developed in 1 case (4%) in Group I, and in 5 cases
(71%) in Group II. CONCLUSION: A distal level of instrumentation ending at the
first lordotic vertebra is not justified and causes violation of sagittal balance
and development of distal junctional kyphosis. The inclusion of a sagittal stable
vertebra in fusion prevents the development of this undesirable situation.
PMID- 26431093
TI - Reconstruction Of Glenoid Bone Deficiency With Porous Titanium Nickelide In
Recurrent Anterior Shoulder Instability.
AB - INTRODUCTION: One of the main causes of recurrent shoulder instability is a bone
defect of the front edge of the glenoid. The available techniques for
reconstruction of this bone defect, however, have some disadvantages. OBJECTIVE:
The aim of this study was to develop a new method that can reduce the number of
postoperative complications and improve the efficiency of surgical treatment of
recurrent anterior shoulder instability with glenoid bone defect. MATERIALS AND
METHODS: We present here a new method for surgical treatment of post-traumatic
recurrent anterior shoulder instability with bony defects using porous NiTi. We
operated 5 patients using this method. Computed tomography was used in the
preoperative preparation of the NiTi graft. The graft was sawed from a
cylindrical billet about 1 cm in thickness. Two screw holes were then made with a
drill. The prepared graft was subsequently installed in the area of the glenoid
bone defect. RESULTS: There were no recurrences of the dislocation after the
surgical treatment. All patients returned to their previous levels of physical
activity. CONCLUSIONS: The proposed method is an alternative to Latarjet
procedure and iliac crest bone grafting. The advantages of this method are
accurate reconstruction of the bone defect, minimal risk of recurrences, no
resorption, and reduction of procedure time.
PMID- 26431094
TI - NLRs Challenge Impacts Tight Junction Claudins In Sertoli Cells.
AB - AIM: The present study aims to investigate the NALP3 system and its effect on
claudins in Sertoli cells using a mouse adult Sertoli cell line as a model. We
focus on the Sertoli cell biology looking for the possible implications for male
reproductive functions. MATERIALS AND METHODS: Adult Sertoli cells were
transfected with NAPL3 siRNA and treated with NOD1 (ie-DAP) and NOD2 (MDP)
receptor ligands. Two dimensional gel electrophoresis was performed on lysates of
non-challenged and MDP-treated Sertoli cells. RESULTS: There were positive
claudin-5 and claudin-11 expression levels on transcript (RT-qPCR) levels.
Specific protein spots in 2D gels were detected after bioinformatics analysis.
This study demonstrates direct induction of tight-junction proteins probably
favouring junction stability. CONCLUSIONS: The innate immunity and tight-junction
pathway integration probably have a protective role for both blood-testis immune
barrier and spermatogenesis compartmentalisation maintained by the very same
barrier. This integration also points the way for mechanistic research of the
disturbances inflicted during an inflammatory response in the testis niche.
PMID- 26431095
TI - Morphological Study Of Border Area Of Pulp-Capping Materials And Er:YAG Laser
Prepared Hard Dental Surface.
AB - INTRODUCTION: Vital pulp therapy involves biologically based therapeutic
activities aimed at restoring health and preserving the vitality of cariously or
traumatically damaged pulp. Adaptation of pulp-capping materials to the prepared
tooth surface may be the key to the success of biological tooth treatment. AIM:
To investigate the area of adaptation of synthetic tricalcium silicate cement,
calcium hydroxide cement and mineral trioxide-aggregate to the dentin surface,
prepared with the help of Er:YAG dental laser. MATERIAL AND METHODS: Four
extracted human tooth cavities were prepared with the help of Er:YAG dental laser
(LiteTouch, Syneron, Israel), establishing microcommunication with the pulp
chamber less than 1 mm in diameter. As pulp-capping materials in the cavities we
used tricalcium silicate cement (Biodentine, Septodont, France), calcium
hydroxide cement (Dycal) and mineral-trioxide aggregate (ProRoot MTA), stirred
and administered according to manufacturers' instructions. The first material
fills the whole cavity and the other two are spread in a thin layer and sealed
with glass ionomer cement. Thus prepared, the samples were left for three days at
37 degrees C in humidified environment. The samples were prepared for scanning
electron microscopy (SEM) by standard methodology. The border area surfaces of
the materials and the dentin were scanned using electron microscopy. RESULTS: The
morphological changes occurring to the Er:YAG laser prepared dentin and the
structural characteristics of the studied pulp-capping materials are demonstrated
using scanograms. The border areas where good contact of materials and dentinal
tubules is established are thoroughly studied. Good adaptation is seen in three
calcium silicate cement, followed by mineral trioxide aggregate and calcium
hydroxide cement. CONCLUSION: The dentin surface, prepared with Er:YAG laser
demonstrates a very good adaptation of the three tested pulp-capping materials.
PMID- 26431097
TI - Cutaneous Leishmaniasis - Dermoscopic Findings And Cryotherapy.
AB - We present a 60-year-old male patient who, three months after a holiday in
Southern Greece, found a small 'pimple' on his back, which gradually got as big
as a small walnut, the central part becoming ulcerated and scabby. Dermatological
examination found an erythematous-to-livid nodular lesion on the right shoulder;
it was 16 mm in diameter with central ulceration, covered with brownish crust
which discharged pus-like secretion upon pressure. Microscope examination of
Romanowsky-Giemsa stained lesion material detected amastigote forms of Leishmania
tropica. The culture investigation and serological tests for leishmaniasis were
negative. Dermoscopy of the lesion found the following features: erythema,
hyperkeratosis, central ulceration covered with brownish crust, "yellow tears
like" structures and "white starburst-like" patterns, and various vascular
structures (including dotted vessels, comma-shaped vessels, hairpin- and
glomerular-like vessels). The patient was diagnosed with cutaneous leishmaniasis
and underwent four cryotherapy sessions every other week with excellent
therapeutic results - complete resolution of infiltrate with subsequent gentle
hypopigmented scarring. In conclusion, dermoscopy is an easily accessible non
invasive method which can be useful for the diagnosis of cutaneous leishmaniasis.
Cryotherapy is the treatment of choice for single skin lesions.
PMID- 26431096
TI - Economic Burden And Health-Related Quality Of Life Of Patients With Cystic
Fibrosis In Bulgaria.
AB - OBJECTIVE: The aim of this study was to determine the economic burden from a
societal perspective and health-related quality of life (HRQOL) of patients with
cystic fibrosis (CF) in Bulgaria. MATERIALS AND METHODS: We conducted a cross
sectional study of 33 patients with CF and 17 caregivers from Bulgaria. Data on
socio-demographic characteristics, health resource utilisation, informal care,
labor productivity losses and HRQOL were collected from questionnaires completed
by patients or their caregivers. HRQOL was evaluated with the EuroQol 5-domain
(EQ-5D-3L) questionnaire. RESULTS: Median annual costs of CF in Bulgaria were ?
24 152 per patient in 2012 as a reference year. Median annual costs for children
were found to be significantly higher than those for adults - ? 31 945 vs. ? 15
714 (p = 0.012). This outcome came from statistically significant differences in
costs for main informal carer (p < 0.001) and costs for other informal carers (p
= 0.022). As a single cost item, drugs had the biggest monetary impact. Median
annual drug costs were ? 13 059. Bulgarian CF patients showed low HRQOL results -
50 median VAS score and 0.592 median health utilities. A quarter of patients even
rated their health state as worse than death. CONCLUSION: CF patients from
Eastern Europe remain a vulnerable population with risk factors for worse health
outcomes. Our study provided a state-of-the art analysis that facilitates the
elaboration, adoption and application of targeted public health policies to
tackle CF-related problems at national and European level.
PMID- 26431098
TI - Thoracic Meningioma In Combination With Severe Lumbar Spinal Stenosis Presenting
With Atypical Neurological Deficit.
AB - We report on a case of a 47-year-old female patient with a long history of low
back pain irradiating bilaterally to the legs. Twenty days before admission to
our clinic, she had developed progressive weakness in the legs, more pronounced
on the left side. The initial neurological examination revealed signs of damage
to both the cauda equina and the spinal cord. The neuroimaging studies (computed
tomography, myelography and magnetic-resonance tomography) found spinal stenosis
most severe at L4-L5 level, and right lateral thoracic intradural-extramedullary
tumor at T9-T10 level. The patient underwent two neurosurgical procedures. The
first stage included microsurgical resection of the thoracic lesion and the
second stage aimed at decompressing the lumbar spinal stenosis. To avoid missing
a diagnosis of thoracic lesions, it is necessary to perform a thorough
neurological examination of the spinal cord motor and sensory functions. In
addition, further MRI examination of upper spinal segment is needed if the
neuroimaging studies of the lumbar spine fail to provide reasonable explanation
for the existing neurological symptoms.
PMID- 26431099
TI - Ulcerated Hemangioma - Surveillance Only.
AB - Infantile hemangiomas are reported in 10-12% of children less than 1 year of age,
with ulceration in about 5-13% of cases. Little is known about the mechanism of
this disease and explanations are still being looked for. We present a 4-month
old female infant with haemangioma on the left buttock; the hemangioma was
noticed at 2 weeks of age, progressively enlarging and ulcerated.
PMID- 26431100
TI - Urothelial Carcinoma Concomitant With Malakoplakia In Non-Functioning
Nephrolithic Kidneys.
AB - Nephrolithic non-functioning kidney and malakoplakia are major health problems.
Kidney function cannot be fulfilled and also this leads to a high risk of
development of urothelial neoplasm. We report herein a case of urothelial
carcinoma concomitant with malakoplakia in non-functioning nephrolithic kidneys.
PMID- 26431101
TI - Suberoylanilide hydroxamic acid (SAHA) promotes the epithelial mesenchymal
transition of triple negative breast cancer cells via HDAC8/FOXA1 signals.
AB - Inhibitor of histone deacetylases (HDACIs) have great therapeutic value for
triple negative breast cancer (TNBC) patients. Interestingly, our present study
reveals that suberoyl anilide hydroxamic acid (SAHA), one of the most advanced
pan-HDAC inhibitor, can obviously promote in vitro motility of MDA-MB-231 and BT
549 cells via induction of epithelial-mesenchymal transition (EMT). SAHA
treatment significantly down-regulates the expression of epithelial markers E
cadherin (E-Cad) while up-regulates the mesenchymal markers N-cadherin (N-Cad),
vimentin (Vim) and fibronectin (FN). However, SAHA has no effect on the
expression and nuclear translocation of EMT related transcription factors
including Snail, Slug, Twist and ZEB. While SAHA treatment down-regulates the
protein and mRNA expression of FOXA1 and then decreases its nuclear
translocation. Over-expression of FOXA1 markedly attenuates SAHA induced EMT of
TNBC cells. Further, silence of HDAC8, while not HDAC6, alleviates the down
regulation of FOXA1 and up-regulation of N-Cad and Vim in MDA-MB-231 cells
treated with SAHA. Collectively, our present study reveals that SAHA can promote
EMT of TNBC cells via HDAC8/FOXA1 signals, which suggests that more attention
should be paid when SAHA is used as anti-cancer agent for cancer treatment.
PMID- 26431102
TI - Synthesis of pyranopyrazolo N-glycoside and pyrazolopyranopyrimidine C-glycoside
derivatives as promising antitumor and antimicrobial agents.
AB - As a part of systematic investigation of the synthesis and biological activities
of pyrazole analogues linked to various heterocyclic systems, a new series of
pyrazolo-N-glycoside derivatives, pyrazolopyranopyrimidine and C-glycoside of
pyrazolopyranotriazolo-pyrimidine derivatives was synthesized through the
reaction of the key intermediate 6-amino-3-methyl-4-(substituted-phenyl)-1,4
dihydropyrano[2,3-c]pyrazole-5-carbonitrile (3a,b) with different reagents.
Structures of the newly synthesized compounds were elucidated by elemental
microanalysis and spectroscopic methods. The compounds were subjected to in vitro
antitumor evaluation using the MTT assay. N-(beta-D-ribofuranosyl)- and N-(beta-D
xylofuranosyl)-6{[(1E)-4-chlorophenyl)-methylene] amino}4-(4-florophenyl)-3
methyl-1,4-dihydropyrano[2,3-c]-pyrazole-5-carbonitrile (6a,b) were the most
active compounds against three human cancer cell lines. Also, most of the newly
synthesized compounds exhibited high activity towards Gram-negative and Gram
positive bacteria. Compound 6a exhibited excellent activity towards bacteria
compared to ofloxacine as the reference drug.
PMID- 26431103
TI - Dissolution profiles of perindopril and indapamide in their fixed-dose
formulations by a new HPLC method and different mathematical approaches.
AB - A new HPLC method was introduced and validated for simultaneous determination of
perindopril and indapamide. Validation procedure included specificity,
sensitivity, robustness, stability, linearity, precision and accuracy. The method
was used for the dissolution test of perindopril and indapamide in three fixed
dose formulations. The dissolution procedure was optimized using different media,
different pH of the buffer, surfactants, paddle speed and temperature. Similarity
of dissolution profiles was estimated using different model-independent and model
dependent methods and, additionally, by principal component analysis (PCA). Also,
some kinetic models were checked for dissolved amounts of drugs as a function of
time.
PMID- 26431104
TI - Conventional versus ultrasound and microwave assisted synthesis: Some new
environmentally friendly functionalized picolinium-based ionic liquids with
potential antibacterial activity.
AB - A green chemistry approach has been adopted for the synthesis of thirty-four new
picolinium-based ionic liquids using microwave (MW) and ultrasound (US)
irradiation as well as conventional thermal heating. Their structures were
confirmed by FT-IR, 1H NMR, 13C NMR, 11B NMR, 19F NMR, 31P NMR, mass spectra and
elemental analyses. The antimicrobial profile of the novel ionic liquids was
evaluated and the minimum inhibitory concentration (MIC) showed their moderate to
low antimicrobial activity against eight types of human pathogens.
PMID- 26431105
TI - Anti-breast cancer activity of some novel quinoline derivatives.
AB - To discover new bioactive lead compounds for medicinal purposes, 2-cyano-3-(4
substituted)-N-(quinolin-3-yl) acrylamide derivatives 2-24, chromenes 25, 26 and
benzochromenes 27, 28 were synthesized. The structures of the newly synthesized
compounds were confirmed by elemental analyses, IR, 1H NMR and 13C NMR
spectroscopies. In addition, the structure of compound 1 was confirmed through X
ray crystallography. All the newly synthesized compounds were evaluated for their
cytotoxic activity against the breast cancer cell line MCF7. The corresponding 2
cyano-3-(4-hydroxy-3-methoxyphenyl)-N-(quinolin-3-yl) acrylamide (15), 3-oxo-N
(quinolin-3-yl)-3H-benzol[f] chromene-2-carboxamide (27), 2-cyano-3-(4
fluorophenyl-N-(quinolin-3-yl) acrylamide (7), 2-cyano-5-(4-(dimethyl-amino)
phenyl)-N-(quinolin-3-yl) penta-2,4-dienamide (19) exhibited higher activity
compared to doxorubicin (with IC50 value of 47.9 MUmol L-1) as a reference drug,
with IC50 values of 29.8, 39.0, 40.0, 40.4 MUmol L-1, resp. Also, quinoline
acrylamides containing 2,3,4-trimethoxyphenyl 17, 2-chlorophenyl 10,
benzo[d][1,3]dioxol 12, 2-methoxynaphthalen 22, 2,4-dichlorophenyl 18 and
quinoline carrying a chromene-3-carboxamide moiety 25 were nearly as active as
doxorubicin, while quinoline acrylamides incorporating unsubstituted phenyl 2, p
tolyl 3, 2,4-dienamide 8, 3-nitrophenyl 13, 4-nitrophenyl 14, 3,4-dimethoxyphenyl
16 and chromene 26 exhibited a moderate activity. In addition, quinoline with
acetamide 1, 4-hydroxyphenyl 4, 4-dimethylaminophenyl 9, 4-chlorophenyl 11, 3
bromophenyl 20, 4-bromophenyl 21 and 3-thienyl moiety 24 showed less activity
than doxorubicin. On the other hand, quinoline having 2-methoxyphenyl 5, 4
methoxyphenyl 6, 4-metho xynaphthalene 23 and chromene-2-carboxamide 28 showed no
activity.
PMID- 26431106
TI - Curcumin phytosomal softgel formulation: Development, optimization and
physicochemical characterization.
AB - Curcumin, a naturally occurring lipophilic molecule can exert multiple and
diverse bioactivities. However, its limited aqueous solubility and extensive
presystemic metabolism restrict its bioavailability. Curcumin phytosomes were
prepared by a simple solvent evaporation method where free flowing powder was
obtained in addition to a newly developed semisolid formulation to increase
curcumin content in softgels. Phytosomal powder was characterized in terms of
drug content and zeta potential. Thirteen different softgel formulations were
developed using oils such as Miglyol 812, castor oil and oleic acid, a
hydrophilic vehicle such as PEG 400 and bioactive surfactants such as Cremophor
EL and KLS P 124. Selected formulations were characterized in terms of curcumin
in vitro dissolution. TEM analysis revealed good stability and a spherical, self
closed structure of curcumin phytosomes in complex formulations. Stability
studies of chosen formulations prepared using the hydrophilic vehicle revealed a
stable curcumin dissolution pattern. In contrast, a dramatic decrease in curcumin
dissolution was observed in case of phytosomes formulated in oily vehicles.
PMID- 26431107
TI - Novel 4-aminoquinazoline derivatives as new leads for anticancer drug discovery.
AB - A novel series of quinazoline derivatives 2-8, 10-12 were designed and
synthesized. Structures of the newly synthesized compounds were confirmed by
elemental analyses, IR, 1H and 13C NMR spectral data. All the newly synthesized
compounds were evaluated for in vitro cytotoxic activity against the breast
cancer cell line MCF-7. Seven of the novel compounds exhibited higher activity
than the reference drug doxorubicin. The corresponding compounds 3, 4, 5, 8, 10,
11 and 12 exhibited higher activity with IC50 values from 22.75 to 43.44 MUmol L
1, compared to the reference drug doxorubicin with IC50 value of 47.90 MUmol L-1.
Also, compounds 1, 6, and 9 are nearly as active as doxorubicin with IC50 values
of 48.31, 48.90, and 48.91 MUmol L-1, respectively, while compounds 2 and 7
exhibited a moderate activity with IC50 values of 50.44 and 52.37 MUmol L-1. In
addition, compound 13 showed no activity. Cytotoxic screening of the tested
compounds offered an encouraging framework that may lead to the discovery of
potent anti-breast cancer activity.
PMID- 26431108
TI - Contribution to diagnostics/prognostics of tuberculosis in children. I. New
methods of assaying zinc and simultaneously copper and zinc in diluted sera by
flame atomic-absorption spectrometry.
AB - In an attempt to provide a reliable status of metal ions in children, new methods
of analysis of children's sera are proposed. New flame atomic-absorption
spectrometric (FAAS) methods are simple, cost- and time-effective and, above all,
labor-, reagent- and sample-saving. Two methods were suggested: method A for
simultaneous determination of Cu and Zn from 5-fold diluted sera, and method B,
for assaying zinc alone in 10-fold diluted samples. Both methods are based on a
single-step sample pretreatment (deproteinization with 3 mol dm-3 HCl). Method A
uses a single-step calibration with a mixed standard. The main advantage of
method B is an additional reduction in sample consumption. Both methods were
fully validated against reference methods. Accuracy, sensitivity and precision
have proven them to be comparable to the reference methods in terms of analytical
performance, and applicable to analyses of children's sera.
PMID- 26431109
TI - Contribution to diagnostics/prognostics of tuberculosis in children. II.
Indicative value of metal ions and biochemical parameters in serum.
AB - Newly introduced methods of assaying simultaneously copper and zinc and zinc
alone in serum by flame atomic-absorption spectrometry are simple and economical,
especially in saving the consumption of serum material. Along with biochemical
parameters, they have been successfully applied to diagnostics/prognostics of
tuberculosis in children, through analyses of sera from pediatric patients with
lung tuberculosis or suspected tuberculosis, enabling the follow-up of
therapeutic efficiency. The prognostic strength of Cu and Cu/Zn ratio together
with C-reactive protein, complement components C3 and C4, and erythrocyte
sedimentation rate have been documented.
PMID- 26431110
TI - Development of a high-throughput screening system for identification of novel
reagents regulating DNA damage in human dermal fibroblasts.
AB - Ultraviolet (UV) radiation is a major inducer of skin aging and accumulated
exposure to UV radiation increases DNA damage in skin cells, including dermal
fibroblasts. In the present study, we developed a novel DNA repair regulating
material discovery (DREAM) system for the high-throughput screening and
identification of putative materials regulating DNA repair in skin cells. First,
we established a modified lentivirus expressing the luciferase and hypoxanthine
phosphoribosyl transferase (HPRT) genes. Then, human dermal fibroblast WS-1 cells
were infected with the modified lentivirus and selected with puromycin to
establish cells that stably expressed luciferase and HPRT (DREAM-F cells). The
first step in the DREAM protocol was a 96-well-based screening procedure,
involving the analysis of cell viability and luciferase activity after
pretreatment of DREAM-F cells with reagents of interest and post-treatment with
UVB radiation, and vice versa. In the second step, we validated certain effective
reagents identified in the first step by analyzing the cell cycle, evaluating
cell death, and performing HPRT-DNA sequencing in DREAM-F cells treated with
these reagents and UVB. This DREAM system is scalable and forms a time-saving
high-throughput screening system for identifying novel anti-photoaging reagents
regulating DNA damage in dermal fibroblasts.
PMID- 26431111
TI - Investigation of the effects of vitamin D and calcium on intestinal motility: In
vitro tests and implications for clinical treatment.
AB - The presence of vitamin D receptors in small intestine muscle cells may lead one
to think that vitamin D may act locally, influencing intracellular calcium
concentration and contributing to the contraction-relaxation regulation of the
intestinal smooth muscle cells. This study investigates the potential effects of
vitamin D and calcium on intestinal motility using an in vitro test. Different
calcium concentrations added to the tissue not pre-treated with 1,25
dihydroxycholecalciferol [1alpha,25(OH)2D3] produced no response at low doses
(1.25 * 10-3 and 2.0 * 10-3 mol L-1) and only a very weak response at higher
concentration (3.0 * 10-3 mol L-1). The addition of 1alpha,25(OH)2D3 (1.44 * 10
10 mol L-1) had no effect on isolated ileum motility. When calcium (3.0 * 10-3
mol L-1) was added after at least 3 hours, it evoked evident and persistent
contractions for 60-90 minutes. The contractions were at about 40 % of the peak
produced by acetylcholine. Thus, simultaneous intake of vitamin D and calcium
might be a useful co-adjuvant in intestinal atony therapy aimed to stimulate
normal gut motility in humans. These findings imply that supplemental vitamin D
may be important in all cases where calcium has to be prescribed.
PMID- 26431117
TI - Validation of the Amsterdam Beverage Picture Set: A Controlled Picture Set for
Cognitive Bias Measurement and Modification Paradigms.
AB - BACKGROUND: Alcohol research may benefit from controlled and validated picture
sets. We have constructed the Amsterdam Beverage Picture Set (ABPS), which was
designed for alcohol research in general and cognitive bias measurement and
modification in particular. Here, we first formulate a position on alcohol
stimulus validity that prescribes that alcohol-containing pictures, compared to
nonalcohol-containing pictures, should induce a stronger urge to drink in heavy
drinkers than in light drinkers. Because a perceptually simple picture might
induce stronger cognitive biases but the presence of a drinking context might
induce a stronger urge to drink, the ABPS contains pictures with and without
drinking context. By limiting drinking contexts to simple consumption scenes
instead of real-life scenes, complexity was minimized. A validation study was
conducted to establish validity, to examine ABPS drinking contexts, and to
explore the role of familiarity, valence, arousal, and control. METHODS: Two
hundred ninety-one psychology students completed the Alcohol Use Disorders
Identification Test, as well as rating and recognition tasks for a subset of the
ABPS pictures. RESULTS: The ABPS was well-recognized, familiar, and heavy
drinkers reported a greater urge to drink in response to the alcohol-containing
pictures only. Alcohol presented in drinking context did not elicit a stronger
urge to drink but was recognized more slowly than alcohol presented without
context. CONCLUSIONS: The ABPS was found to be valid, although pictures without
context might be preferable for measuring cognitive biases than pictures with
context. We discuss how an explicit approach to picture construction may aid in
creating variations of the ABPS. Finally, we describe how ABPS adoption across
studies may allow more reproducible and comparable results across paradigms,
while allowing researchers to apply picture selection criteria that correspond to
a wide range of theoretical positions. The latter is exemplified by ABPS
derivatives and adoptions that are currently under way.
PMID- 26431118
TI - Cap-aspiration lumpectomy for small submucosal tumors originating from the
muscularis propria of the gastric fundus: a preliminary study (with videos).
AB - OBJECTIVE: Small fundal submucosal tumors (SMTs) originated from the muscularis
propria pose great difficulties to conventional therapies. We aimed to evaluate
the feasibility and safety of endoscopic cap-aspiration lumpectomy (CASL) as a
new and simple full-thickness resection for the treatment of small fundal SMTs.
METHODS: From July 2013 to February 2014, patients with small fundal SMTs of <=10
mm in diameter that were originated from muscularis propria were included in the
study. CASL was performed by suctioning SMTs into a transparent cap, ligating
with a metal snare and resecting the tumors. The wall deficit was closed by using
endoclips. RESULTS: Altogether 28 patients were included in the study. CASL
achieved an en bloc resection rate of 100%, with a mean total procedure time of
23.9 min. Active perforation was found in 20 (71.4%) patients, and endoclips
closed the wall defect in all 20 cases. One patient developed pneumoperitoneum
and self-limited peritonitis was found in two patients, all of whom were managed
successfully. Pathological examination showed that 71.4% (20/28) of the tumors
were gastrointestinal stromal tumors. No tumor recurrence was observed during the
follow-up. CONCLUSIONS: CASL may be a feasible and safe full-thickness resection
modality for the treatment of small fundal SMTs arising from the muscularis
propria. Further randomized studies are needed to confirm the results.
PMID- 26431119
TI - Palladium(II)-Catalyzed Formal [3 + 2] Cycloaddition of Aziridines with 3
Substituted Indoles: Synthesis of Enantioenriched Pyrroloindolines.
AB - A Pd-catalyzed enantiospecific formal [3 + 2] cycloaddition between chiral
aziridines and indoles has been developed. With this method, chiral
pyrroloindolines in enantiomerically pure forms were constructed in high yields
and diastereoselectivities under mild conditions.
PMID- 26431116
TI - Commonalities and Distinctions Among Mechanisms of Addiction to Alcohol and Other
Drugs.
AB - BACKGROUND: Alcohol abuse is comorbid with abuse of many other drugs, some with
similar pharmacology and others quite different. This leads to the hypothesis of
an underlying, unitary dysfunctional neurobiological basis for substance abuse
risk and consequences. METHODS: In this review, we discuss commonalities and
distinctions of addiction to alcohol and other drugs. We focus on recent advances
in preclinical studies using rodent models of drug self-administration. RESULTS:
While there are specific behavioral and molecular manifestations common to
alcohol, psychostimulant, opioid, and nicotine dependence, attempts to propose a
unifying theory of the addictions inevitably face details where distinctions are
found among classes of drugs. CONCLUSIONS: For alcohol, versus other drugs of
abuse, we discuss and compare advances in: (i) neurocircuitry important for the
different stages of drug dependence; (ii) transcriptomics and genetical genomics;
and (iii) enduring effects, noting in particular the contributions of behavioral
genetics and animal models.
PMID- 26431120
TI - Effects of Systemic Magnesium on Post-operative Analgesia: Is the Current
Evidence Strong Enough?
AB - BACKGROUND: Clinical studies have been previously carried out on the efficacy of
systemic magnesium to minimize postoperative pain, however, with controversial
results. A quantitative meta-analysis was performed to evaluate the analgesic
efficacy and safety of systemic magnesium on post-operative pain. STUDY DESIGN:
Comprehensive systematic review of all relevant, publsished randomized controlled
trials. METHODS: A search was conducted of published literature in MEDLINE,
PsycINFO, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials
(CENTRAL) databases from inception to Sep-Oct 2014. Randomized controlled trials
(RCTs) that compared magnesium with placebo were identified. Effects were
summarized using standardized mean differences (SMDs), weighed mean differences
(WMD), or odds ratio (OR) with suitable effect model. RESULTS: Twenty-seven RCTs
involving 1,504 patients were included. In total, peri-operative magnesium
significantly reduced the pain score at rest (SMD, -1.43, 95% CI, -2.74 to -0.12,
< 0.01). Magnesium significantly reduced analgesic consumption (SMD, -1.72, 95%
CI, -3.21 to -0.23) in patients undergoing urogenital, orthopaedic, and
cardiovascular surgeries, but was inconclusive for patients receiving
gastrointestinal surgeries. The obvious analgesia of systemic magnesium was
observed on reducing the pain score during movement at 24 hours after operation
(SMD, -0.05, 95% CI, -0.43 to 0.32). Moreover, magnesium administration showed a
beneficial effect with regard to intra-operative hemodynamics and reduced
extubation time in the cardiovascular surgery patients (WMD, -29.34 min, 95% CI,
35.74 to -22.94, P < 0.01). LIMITATIONS: Focused only on the quality of analgesia
on postoperative pain with regards to surgery type. CONCLUSIONS: Our study
suggests that systemic magnesium during general anesthesia significantly
decreases post-operative pain scores without increasing adverse events. It should
be noted that since there are 18 ongoing RCTs without published data, it is still
premature to draw conclusions on the long-term analgesic effects of magnesium as
well as potential gender or age difference.
PMID- 26431121
TI - The Association of rs4753426 Polymorphism in the Melatonin Receptor 1B (MTNR1B)
Gene and Susceptibility to Adolescent Idiopathic Scoliosis: A Systematic Review
and Meta-analysis.
AB - BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a tridimensional structural
deformity of the spine that may deteriorate progressively, leading to significant
functional limitations and pain problems. Several previous studies have
implicated the rs4753426 single nucleotide polymorphism in the melatonin receptor
1B (MTNR1B) gene in the etiology of AIS. However the sample sizes were limited
and the findings of those studies were inconsistent. An overall assessment of the
evidence supporting this association has not been previously conducted.
OBJECTIVES: To provide a comprehensive assessment and synthesis of the currently
available evidence on the association between rs4753426 and AIS. STUDY DESIGN: A
systematic review and meta-analysis. SETTING: University hospital, China.
METHODS: This review followed the Preferred Reporting Items for Systematic Review
and Meta-Analyses guidelines. PubMed (MEDLINE), EMBASE, Scopus databases, and
WANFANG databases were systematically searched through December 2014 to identify
relevant studies following a sensitive strategy. Statistical analysis was
performed using the Review Manager 5.2 software. Summary odds ratios (ORs) and
corresponding 95% confidence intervals (CIs) were estimated using the fixed
effect inverse variance model for allelic (C vs. T) and genotypic comparisons.
RESULTS: Four papers including 5 studies which involved 2,552 AIS cases and 2,738
controls were identified for this meta-analysis. The results showed that C allele
of the rs4753426 was significantly associated with AIS (OR = 1.12, 95% CI: 1.03
1.21, P = 0.01). CT and CC genotypes were 26% (OR = 1.26, 95% CI: 1.04-1.53, P =
0.01) and 28% (OR = 1.28, 95% CI: 1.05-1.56, P = 0.01), respectively, more likely
to have AIS compared with CC genotype. As for the dominant model (CC+TT vs. TT),
summary ORs showed statistically significant association with AIS (OR = 1.28, 95%
CI: 1.06-1.53, P = 0.009). Compared with the CT+TT genotype, the summary ORs of
the CC genotype showed marginally statistically significant association with AIS
(OR = 1.11, 95 % CI: 0.99-1.24, P = 0.07). The subgroup meta-analysis results
showed the C allele and each genotype were significantly associated with AIS in
the Asian group but not in the Caucasian group. LIMITATIONS: Paucity of available
literature. CONCLUSIONS: To our knowledge, there has been no meta-analysis to
analyze the association between rs4753426 polymorphism in the MTNR1B gene and
AIS. This systematic review was a comprehensive analysis of the currently
available evidence, and found an overall significant association of rs4753426
polymorphism with the risk of AIS, especially in the Asian population. Further
investigation of this association is necessary in other populations.
PMID- 26431122
TI - Predictors of Persistent Neuropathic Pain--A Systematic Review.
AB - BACKGROUND: Characterization of the prognostic variables for persistent
neuropathic pain (PNP) remains incomplete despite multiple articles addressing
this topic. To provide more insight into the recovery and prognosis of
neuropathic pain, high-quality data are required that provide information about
the predictors that contribute to the development of PNP. OBJECTIVE: To determine
the methodological quality of studies about predictors for PNP and to summarize
findings of predictors found in high-quality studies. STUDY DESIGN: A systematic
review. SETTING: VU University Medical Center, Amsterdam, The Netherlands.
METHODS: Studies were identified by searching the electronic databases PubMed,
Embase, and Cochrane Library. Methodological quality of each article was
independently assessed by 2 reviewers. RESULTS: Forty-six relevant studies were
identified, classified into 4 different neuropathic pain (NP)-syndromes:
postherpetic neuralgia (n = 35), radicular pain and sciatica (n = 3),
postsurgical pain (n = 6), and other types of NP (n = 2). Seven studies were of
high quality. The 3 high-quality studies found for PHN reported male gender,
older age, smoking, trauma at the site of lesion, missed antiviral prescriptions,
higher acute pain severity, higher rash severity, more neuropathic
characteristics, shorter rash duration, and a lower health status as predictors
for PNP. For persistence of radicular pain one high-quality study reported
negative outcome expectancies, pain-related fear of movement, and passive pain
coping as predictors for PNP. Psychological distress, acute pain, breast cancer
surgery, higher body mass index, area of secondary hyperalgesia, neuropathic
characteristics, hypoesthesia, and hyperesthesia were found to be predictive for
postsurgical pain in 3 high-quality studies. LIMITATIONS: Some publications may
have been missed during literature search. The low-quality of the studies could
be the result of an incomplete description of their methods. CONCLUSIONS: High
quality studies mainly assessed factors related to disease functions and
structures. Due to shortcomings in methodological quality and limited areas of
predictor selection, there is a need for high-quality studies focusing on
predictor measurement, statistical analysis and the use of a standardized set of
predictors.
PMID- 26431123
TI - Effect of Individually Tailored Biopsychosocial Workplace Interventions on
Chronic Musculoskeletal Pain and Stress Among Laboratory Technicians: Randomized
Controlled Trial.
AB - BACKGROUND: Chronic musculoskeletal pain is prevalent among laboratory
technicians and work-related stress may aggravate the problem. OBJECTIVES: This
study investigated the effect of a multifaceted worksite intervention on pain and
stress among laboratory technicians with chronic musculoskeletal pain using
individually tailored physical and cognitive elements. STUDY DESIGN: This trial
uses a single-blind randomized controlled design with allocation concealment in a
2-armed parallel group format among laboratory technicians. The trial
"Implementation of physical exercise at the Workplace (IRMA09)--Laboratory
technicians" was registered at ClinicalTrials.gov prior to participant enrolment.
SETTING: The study was conducted at the head division of a large private
pharmaceutical company's research and development department in Denmark. The
study duration was March 2014 (baseline) to July 2014 (follow-up). METHODS:
Participants (n = 112) were allocated to receive either physical, cognitive, and
mindfulness group-based training (PCMT group) or a reference group (REF) for 10
weeks at the worksite. PCMT consisted of 4 major elements: 1) resistance training
individually tailored to the pain affected area, 2) motor control training, 3)
mindfulness, and 4) cognitive and behavioral therapy/education. Participants of
the REF group were encouraged to follow ongoing company health initiatives. The
predefined primary outcome measure was pain intensity (VAS scale 0-10) in average
of the regions: neck, shoulder, lower and upper back, elbow, and hand at 10 week
follow-up. The secondary outcome measure was stress assessed by Cohen's perceived
stress questionnaire. In addition, an explorative dose-response analysis was
performed on the adherence to PCMT with pain and stress, respectively, as outcome
measures. RESULTS: A significant (P < 0.0001) treatment by time interaction in
pain intensity was observed with a between-group difference at follow-up of -1.0
(95%CI: -1.4 to -0.6). No significant effect on stress was observed (treatment by
time P = 0.16). Exploratory analyses for each body region separately showed
significant pain reductions of the neck, shoulders, upper back and lower back, as
well as a tendency for hand pain. Within the PCMT group, general linear models
adjusted for age, baseline pain, and stress levels showed significant
associations for the change in pain with the number of physical-cognitive
training sessions per week (-0.60 [95%CI -0.95 to -0.25]) and the number of
mindfulness sessions (0.15 [95%CI 0.02 to 0.18]). No such associations were found
with the change in stress as outcome. LIMITATIONS: Limitations of behavioral
interventions include the inability to blind participants to which intervention
they receive. Self-reported outcomes are a limitation as they may be influenced
by placebo effects and outcome expectations. CONCLUSIONS: We observed significant
reductions in chronic musculoskeletal pain following a 10-week individually
adjusted multifaceted intervention with physical training emphasizing dynamic
joint mobility and mindfulness coupled with fear-avoidance and de-catastrophizing
behavioral therapy compared to a reference group encouraged to follow on-going
company health initiatives. A higher dose of physical-cognitive training appears
to facilitate pain reduction, whereas a higher dose of mindfulness appears to
increase pain. Hence, combining physical training with mindfulness may not be an
optimal strategy for pain reduction. TRIAL REGISTRATION: NCT02047669.
PMID- 26431124
TI - Intraarticular Facet Injections for Low Back Pain: Design Considerations,
Consensus Methodology to Develop the Protocol for a Randomized Controlled Trial.
AB - BACKGROUND: Since the publication of guidelines by the UK National Institute for
Health and Care Excellence (NICE) and the American Pain Society guidelines for
low back pain in 2009 there have been deep divisions in the pain treatment
community about the use of therapeutic intraarticular facet joint injections.
While evidence for the effectiveness or not of intraarticular facet joint
injections remains sparse, uncertainty will remain. The Warwick feasibility
study, along with a concurrent study with a different design led by another
group, aims to provide a stable platform from which the effectiveness and cost
effectiveness of intraarticular facet joint injections added to normal care could
be evaluated in randomized controlled trials (RCTs). OBJECTIVES: To reach
consensus on key design considerations for the Warwick facet feasibility study
from which the study protocol and working manuals will be developed. STUDY
DESIGN: A consensus conference involving expert professionals and lay members.
METHODS: Preliminary work identified 5 key design considerations for deliberation
at our consensus conference. Three concerned patient assessment and treatment:
diagnosis of possible facet joint pain, interaarticular facet joint injection
technique, and best usual care. Two concerned trial analysis: a priori sub-groups
and minimally important difference and are reported elsewhere. We did systematic
evidence reviews of the design considerations and summarized the evidence. Our
design questions and evidence summaries were distributed to all delegates. This
formed the basis for discussions on the day. Clinical experts in all aspects of
facet joint injection from across the UK along with lay people were invited via
relevant organizations. Nominal group technique was used in 15 facilitated
initial small group discussions. Further discussion and ranking was undertaken in
plenary. All small group and plenary results were recorded and checked and
verified post conference. Where necessary participants were contacted via email
to resolve outstanding issues. RESULTS: Fifty-two delegates attended the
conference with lay people and all relevant professions represented. Consensus
was reached on the details of how to assess patients for facet joint pain,
undertake the injections, and deliver usual care. Where post conference checking
of results revealed errors in calculating ranking results on the day, consensus
was reached by email consultation. All but 3 delegates agreed to be associated
with the outcome. LIMITATIONS: Allocating one day for discussing a wide range of
topics imposed time pressure on discussion and calculation of the numerous
rankings. CONCLUSIONS: Through the use of an evidence-based, systematic,
inclusive, and transparent process we have established consensus from expert
health professionals in the UK, with lay input, on the clinical assessment of
suspected facet joint pain, interaarticular injection for facet joint pain, and
best usual care for use in a feasibility study for a proposed pragmatic clinical
trial of interaarticular facet joint injections. This provides a strong basis for
a clinical trial that will be acceptable to the pain treatment community.
PMID- 26431125
TI - Radiologic Analysis and Clinical Study of the Upper One-third Joint Technique for
Fluoroscopically Guided Sacroiliac Joint Injection.
AB - BACKGROUND: Sacroiliac intraarticular injection by the traditional technique can
be challenging to perform when the joint is covered with osteophytes or is
extremely narrow. OBJECTIVE: To examine whether there is enough space for the
needle to be advanced from the L5-S1 interspinous space to the upper one-third
sacroiliac joint (SIJ) by magnetic resonance image (MRI) analysis as an
alternative to fluoroscopically guided SIJ injection with the lower one-third
joint technique, and to determine the feasibility of this novel technique in
clinical practice. STUDY DESIGN: MRI analysis and observational study. SETTING:
An interventional pain management practice at a university hospital. METHODS: We
analyzed 200 axial T2-weighted MRIs between the L5 and S1 vertebrae of 100
consecutive patients. The following measurements were obtained on both sides: 1)
the thickness of fat in the midline; 2) the distance between the midline (Point
C) and the junction (Point A) of the skin and the imaginary line that connects
the SIJ and the most medial cortex of the ilium; 3) the distance between the
midline (Point C) and the junction (Point B) of the skin and the imaginary line
that connects the SIJ and the L5 spinous process; 4) the distance between the SIJ
and midline (Point C) on the skin, or between the SIJ and the midpoint (Point C')
of the line from Point A to Point B; and 5) the angle between the sagittal line
and the imaginary line that connects the SIJ and the midline on the skin. The
upper one-third joint technique was performed to establish the feasibility of the
alternative technique in 20 patients who had unsuccessful sacroiliac
intraarticular injections using the lower one-third joint technique. RESULTS: The
mean distances from the midline to Point A and to Point B were 21.9 +/- 13.7 mm
and 27.8 +/- 13.6 mm, respectively. The mean distance between the SIJ and Point C
(or Point C') was 81.0 +/- 13.3 mm. The angle between the sagittal line and the
imaginary line that connects the SIJ and the midline on the skin was 42.8 +/- 5.1
degrees . The success rate of sacroiliac intraarticular injections with the upper
one-third joint technique was 90% (18/20). LIMITATIONS: This was an observational
study and lacked a control group. CONCLUSIONS: Sacroiliac intraarticular
injections with the upper one-third joint technique are advisable when it is hard
to perform them with the lower one-third joint technique.
PMID- 26431127
TI - In errata.
PMID- 26431126
TI - Peripheral Nerve Stimulation for the Treatment of Chronic Intractable Headaches:
Long-term Efficacy and Safety Study.
AB - BACKGROUND: Despite the various modalities available for treating headaches,
typical therapy does not provide adequate pain relief for some patients.
OBJECTIVES: This study explored the efficacy and safety of long-term peripheral
nerve stimulation (PNS) for intractable chronic headaches. STUDY DESIGN:
Retrospective study of refractory headache patients at academic pain center.
METHODS: The medical records of all patients (N = 46) permanently implanted with
PNS between January 2005 and January 2012 were reviewed retrospectively. Patient
records and phone interviews were used to quantify the levels of pain intensity,
headache days per month, and overall patient satisfaction with treatment. The
correlation between headache duration and effectiveness of PNS was also assessed.
RESULTS: Pain intensity on the 11-point Numeric Rating Scale decreased from 7.60
+/- 1.73 before implantation to 3.78 +/- 2.41, 3.32 +/- 2.67, 3.42 +/- 2.74, and
2.04 +/- 2.27 at one, 6, 12, and > 12 (19-98) months after implantation,
respectively (P < .001). The mean number of headache days per month decreased by
about 14 days from the base line. No correlation (r = -.33) was found between the
number of years the patients had suffered from headaches and the efficacy of
treatment. LIMITATIONS: Due to the limitation of a retrospective study, the data
collected via chart reviews and phone interviews are susceptible to selection and
information biases. CONCLUSIONS: PNS is an effective modality in the long-term
management of intractable chronic headaches. Despite long histories of chronic
headaches, the majority of patients had significant reductions in pain scores and
the number of headache days per month. The outcomes were not dependent on the
number of years the patients had suffered from headaches before PNS treatment.
PMID- 26431128
TI - Survival Strategies for Tsunami of ICD-10-CM for Interventionalists: Pursue or
Perish!
AB - The unfunded mandate for the implementation of International Classification of
Diseases, 10th Revision, Clinical Modification (ICD-10-CM) is scheduled October
1, 2015. The development of ICD-10-CM has been a complicated process. We have
endeavored to keep Interventional Pain Management doctors apprised via a variety
of related topical manuscripts. The major issues relate to the lack of formal
physician participation in its preparation. While the American Health Information
Management Association (AHIMA) and American Hospital Association (AHA) as active
partners in its preparation. Centers for Medicare and Medicaid Services (CMS) and
Centers for Disease Control and Prevention (CDC) are major players; 3M and Blue
Cross Blue Shield Association are also involved. The cost of ICD-10-CM
implementation is high, similar to the implementation of electronic health
records (EHRs), likely consuming substantial resources. While ICD-10, utilized
worldwide, includes 14,400 different codes, ICD-10-CM, specific for the United
States, has expanded to 144,000 codes, which also includes procedural coding
system. It is imperative for physicians to prepare for the mandatory
implementation. Conversion from ICD-9-CM to ICD-10-CM coding in interventional
pain management is not a conversion of one to one that can be easily obtained
from software packages. It is a both a difficult and time-consuming task with
each physician, early on, expected to spend on estimation at least 10 minutes per
visit on extra coding for established and new patients. For interventional pain
physicians, there have been a multitude of changes, including creation of new
codes and confusing conversion of existing codes. This manuscript describes a
variety of codes that are relevant to interventional pain physicians and often
utilized in daily practices. It is our objective that this manuscript will
provide coding assistance to interventional pain physicians.
PMID- 26431129
TI - Systematic Review of the Diagnostic Accuracy and Therapeutic Effectiveness of
Sacroiliac Joint Interventions.
AB - BACKGROUND: The sacroiliac joint is well known as a cause of low back and lower
extremity pain. Prevalence estimates are 10% to 25% in patients with persistent
axial low back pain without disc herniation, discogenic pain, or radiculitis
based on multiple diagnostic studies and systematic reviews. However, at present
there are no definitive management options for treating sacroiliac joint pain.
OBJECTIVE: To evaluate the diagnostic accuracy and therapeutic effectiveness of
sacroiliac joint interventions. STUDY DESIGN: A systematic review of the
diagnostic accuracy and therapeutic effectiveness of sacroiliac joint
interventions. METHODS: The available literature on diagnostic and therapeutic
sacroiliac joint interventions was reviewed. The quality assessment criteria
utilized were the Quality Appraisal of Reliability Studies (QAREL) checklist for
diagnostic accuracy studies, Cochrane review criteria to assess sources of risk
of bias, and Interventional Pain Management Techniques-Quality Appraisal of
Reliability and Risk of Bias Assessment (IPM-QRB) criteria for randomized
therapeutic trials and Interventional Pain Management Techniques-Quality
Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies
(IPM-QRBNR) for observational therapeutic assessments. The level of evidence was
based on a best evidence synthesis with modified grading of qualitative evidence
from Level I to Level V. Data sources included relevant literature published from
1966 through March 2015 that were identified through searches of PubMed and
EMBASE, manual searches of the bibliographies of known primary and review
articles, and all other sources. OUTCOME MEASURES: For the diagnostic accuracy
assessment, and for the therapeutic modalities, the primary outcome measure of
pain relief and improvement in functional status were utilized. RESULTS: A total
of 11 diagnostic accuracy studies and 14 therapeutic studies were included. The
evidence for diagnostic accuracy is Level II for dual diagnostic blocks with at
least 70% pain relief as the criterion standard and Level III evidence for single
diagnostic blocks with at least 75% pain relief as the criterion standard. The
evidence for cooled radiofrequency neurotomy in managing sacroiliac joint pain is
Level II to III. The evidence for conventional radiofrequency neurotomy,
intraarticular steroid injections, and periarticular injections with steroids or
botulinum toxin is limited: Level III or IV. LIMITATIONS: The limitations of this
systematic review include inconsistencies in diagnostic accuracy studies with a
paucity of high quality, replicative, and consistent literature. The limitations
for therapeutic interventions include variations in technique, variable
diagnostic standards for inclusion criteria, and variable results. CONCLUSION:
The evidence for the accuracy of diagnostic and therapeutic effectiveness of
sacroiliac joint interventions varied from Level II to Level IV.
PMID- 26431130
TI - Improving Analgesic Efficacy and Safety of Thoracic Paravertebral Block for
Breast Surgery: A Mixed-Effects Meta-Analysis.
AB - BACKGROUND: While most trials of thoracic paravertebral nerve blocks (TPVB) for
breast surgery show benefit, their effect on postoperative pain intensity, opioid
consumption, and prevention of chronic postsurgical pain varies substantially
across studies. Variability may result from use of different drugs and
techniques. OBJECTIVES: To examine the use of TPVB in breast surgery, and to
determine which method(s) provide optimal efficacy and safety. STUDY DESIGN:
Mixed-Effects Meta-Analysis. METHODS: We conducted a systematic review of
randomized trials comparing TPVB to no intervention using random-effects models.
To evaluate the contributions of various techniques, clinical approaches were
included as moderators in mixed-effects models. RESULTS: A total of 24 randomized
controlled trials (RCTs) with 1,822 patients were included. Use of TPVB decreased
postoperative pain scores at rest and movement at the first 2, 24, 48, and 72
hours. TPVB modestly decreased intraoperative and postoperative opioid
consumption, reduced nausea and vomiting, and shortened hospitalization, but to a
probably clinically irrelevant degree. Blocks also appeared to reduce the
incidence of chronic postsurgical pain at 6 months. Adding fentanyl to the TPVB
improved pain at rest (at 24, 48, and 72 hours) and movement (at 24 and 72
hours). Multilevel blocks provided better postoperative pain control, but only
during movement (at 2, 48, and 72 hours). Fewer procedural complications
(especially hypotension, epidural spread, and Horner's syndrome) occurred when
anatomical landmarks were supplemented with ultrasound guidance. LIMITATIONS: The
number of studies available was limited in the meta-analytic model of incidence
of chronic post-surgical pain. CONCLUSION: TPVB reduces postoperative pain and
opioid consumption, and has a limited beneficial effect on the quality of
recovery. From all the techniques that were evaluated, only the addition of
fentanyl, and performing multilevel blocks were associated with improved acute
analgesia. TPVB may reduce chronic postsurgical pain at 6 months.
PMID- 26431131
TI - Value of Examination Under Fluoroscopy for the Assessment of Sacroiliac Joint
Dysfunction.
AB - BACKGROUND: Pain emanating from the sacroiliac (SI) joint can have variable
radiation patterns. Single physical examination tests for SI joint pain are
inconsistent with multiple tests increasing both sensitivity and specificity.
OBJECTIVE: To evaluate the use of fluoroscopy in the diagnosis of SI joint pain.
STUDY DESIGN: Prospective double blind comparison study. SETTING: Pain clinic and
radiology setting in urban Veterans Administration (VA) in New Orleans,
Louisiana. METHODS: Twenty-two adult men, patients at a southeastern United
States VA interventional pain clinic, presented with unilateral low back pain of
more than 2 months' duration. Patients with previous back surgery were excluded
from the study. Each patient was given a Gapping test, Patrick (FABERE) test, and
Gaenslen test. A second blinded physician placed each patient prone under
fluoroscopic guidance, asking each patient to point to the most painful area.
Pain was provoked by applying pressure with the heel of the palm in that area to
determine the point of maximum tenderness. The area was marked with a radio
opaque object and was placed on the mark with a fluoroscopic imgage. A site
within 1 cm of the SI joint was considered as a positive test. This was followed
by a diagnostic injection under fluoroscopy with 1 mL 2% lidocaine. A positive
result was considered as more than 2 hours of greater than 75% reduction in pain.
Then, in 2-3 days this was followed by a therapeutic injection under fluoroscopy
with 1 mL 0.5% bupivacaine and 40 mg methylprednisolone. RESULTS: Each patient
was reassessed after 6 weeks. The sensitivity and specificity in addition to the
positive and negative predictive values were determined for both the conventional
examinations, as well as the examination under fluoroscopy. Finally, a receiver
operating characteristic (ROC) curve was constructed to evaluate test
performance. The sensitivity and specificity of the fluoroscopic examination were
0.82 and 0.80 respectively; Positive predictive value and negative predictive
value were 0.93 and 0.57 respectively. The area under ROC curve was 0.812 which
is considered a "good" test; however the area under ROC for the conventional
examination were between 0.52-0.58 which is considered "poor to fail".
LIMITATIONS: Variation in anatomy of the SI joint, small sample size.
CONCLUSIONS: Multiple structures of the SI joint complex can result in clinical
symptoms of pain. These include intra-articular structures (degenerative
arthritis, and inflammatory conditions) as well as extra-articular structures
(ligaments, muscles, etc.).
PMID- 26431132
TI - Contrast Dispersion Pattern and Efficacy of Corticosteroid at the Glenohumeral
Joint in Adhesive Capsulitis.
AB - BACKGROUND: Corticosteroid injection has a wide range of success in adhesive
capsulitis but the reason for this has not yet been explained. We hypothesized
that this difference might be due to the distribution of the corticosteroids
injected into the joint cavity because particulate steroid deposits in the
capsule and will not be moved over time by shoulder motion. OBJECTIVES: The
purpose of this study is to determine whether the therapeutic efficacy of
particulate corticosteroid injection into the glenohumeral joint differs
according to the dispersion pattern. STUDY DESIGN: Prospective evaluation.
SETTING: Outpatient clinics at a tertiary university hospital. METHODS: Seventy
two patients diagnosed as having adhesive capsulitis received a corticosteroid
injection at the glenohumeral joint. The posterior capsule and the subscapular
bursa were selected as dispersion sites and the dispersion of contrast dye was
expressed as a ratio (%). Two weeks and 3 months after the injection clinical
improvement ("not improved," "slightly improved," "much improved"), numeric
rating scale (NRS), and passive range of motions (PROM) were evaluated. The
dispersion of the contrast dye was compared according to the clinical
improvements by an analysis of variance test. Pearson correlation test was done
to find the relationship between PROM and the dispersion and between change of
NRS and the dispersion. RESULTS: The distribution in the subscapular area was
30.0% in the "much improved" group, 22.0% in the "slightly improved" group, and
37.1% in the "no improvement" group which was not significantly different (P =
0.179). Correlations between changes of NRS and the dye distribution were not
statistically significant (P = 0.429 at 2 weeks and P = 0.629 at 3 months). The
change of passive external rotation 3 months after the injection was
significantly correlated with the dye distribution (P = 0.035). LIMITATIONS:
Because of diverse pathologic findings in adhesive capsulitis, further studies
will be needed to address the effect of the dye distribution on the pain
improvement according to pathologic findings revealed by magnetic resonance
imaging (MRI). CONCLUSION: External rotation of the shoulder in adhesive
capsulitis has greater improvement as the corticosteroid solutions injected into
the glenohumeral joint are increasingly dispersed to the subscapularis area.
However, this does not affect the pain improvement after the injection.
PMID- 26431133
TI - Effectiveness and Safety of Pulsed Radiofrequency Treatment Guided by Computed
Tomography for Refractory Neuralgia of Infraorbital Nerve: A Pilot Study.
AB - BACKGROUND: There is no truly optimal treatment to cure refractory neuralgia of
the infraorbital nerve. Recently, nondestructive pulsed radiofrequency (PRF) has
become one of the most attractive interventional techniques for painful
disorders. However, use of the technique for infraorbital neuralgia has been
seldom reported. OBJECTIVE: The purpose of this prospective study is to observe
the effectiveness and safety of PRF treatment for neuralgia of the infraorbital
nerve. STUDY DESIGN: Prospective case series clinical outcome study. SETTING:
University Medical Center, Beijing, China. METHODS: From January 2011 to November
2012, 36 consecutive patients, following ineffective conservative therapy,
underwent PRF treatment and completed 2-year follow-up. Numeric rating scales
(NRS), effective rate, additional carbamazepine dosage, and side effects were
recorded at postoperative day one, week one, week 2, month one, month 3, month 6,
year one, and year 2. Patients were divided into effective group and ineffective
group based on postoperative one -month total pain relief or more than 50%
reduction in NRS and patients were satisfied with the effect, and possible
factors affecting efficacy were compared between the 2 groups. RESULTS: Effective
rates were 69%, 69%, 64%, 50%, and 50% at postoperative month one, month 3, month
6, year one, and year 2, respectively. No serious side effects were observed,
except that 9 patients felt short-term (one -month duration) mild numbness.
Output voltage and tissue resistance in the effective group were significantly
higher than the ineffective group (P < 0.01). Intraoperative output voltage was
negatively correlated with postoperative one -month NRS (r = -0.332, P < 0.05).
LIMITATIONS: The non-controlled and single-centered design of the study.
CONCLUSIONS: Results demonstrated PRF treatment under computed tomography (CT)
guidance for infraorbital neuralgia is safe, effective, and is expected to become
an alternative for patients experiencing ineffective conservative therapy.
Increasing the output voltage of PRF could be the chosen method to improve the
efficacy.
PMID- 26431134
TI - Effect of the Location of Endplate Cement Extravasation on Adjacent Level
Fracture in Osteoporotic Patients Undergoing Vertebroplasty and Kyphoplasty.
AB - BACKGROUND: The most widely researched risk/complication following vertebroplasty
(VP) or kyphoplasty (KP) is that of adjacent level fracture (ALF). Current
literature results regarding the effect of intradiscal extravasation of cement on
the risk of ALF is conflicting with about half of the studies concluding there is
no added risk with endplate extravasation and half of the studies reporting
opposite conclusions. OBJECTIVE: The purpose of the study is to further stratify
the data to determine whether specifically the location and extent of endplate
cement extravasation more strongly affect ALF risk in osteoporotic patients
following either VP or balloon KP. STUDY DESIGN: Retrospective cohort study.
SETTING: University teaching hospital. METHODS: One hundred and fifty-six
cemented levels in 80 patients, treated at a single center between 2008 and 2012
were reviewed. Age, gender, T-score, body mass index, and osteoporosis type
(primary or secondary) were recorded. An ALF was defined as a fracture: 1) in a
non-cemented vertebra; 2) adjacent to a cemented level; and 3) not due to trauma
or malignancy. Location of the cement extravasation (anterior, middle, or
posterior third of the vertebral body) and extravasation extent (percentage of
the intervertebral disc height occupied by the bolus) were measured. A logistic
modeling strategy permitted examining the association between the location and
extent of extravasation and the odds of ALF. RESULTS: ALF occurred in 14 of the
52 patients (27%) and 20 of the 98 levels (20.4%) remaining after exclusions.
Odds of ALF were 5.9 times higher (95% CI: 1.6 to 21.2, P = 0.008) with
extravasation when compared to no leakage. Odds of ALF in a given patient were
22.6 times higher (95% CI: 3.0 to 170.9, P = 0.003) with anterior extravasation
when compared to no leakage. Leakage in the middle or posterior thirds and extent
of extravasation were not associated with ALF. LIMITATIONS: Limitations of the
study include the retrospective study design and small sample size as well as the
retrospective implementation of follow-up criteria posing risk of selection bias.
CONCLUSIONS: Cement endplate extravasation isolated to the anterior third of the
vertebral body is associated with is significantly higher odds of ALF after VP or
KP in patients with osteoporosis.
PMID- 26431135
TI - Lidocaine Injection in the Intramuscular Innervation Zone Can Effectively Treat
Chronic Neck Pain Caused by MTrPs in the Trapezius Muscle.
AB - BACKGROUND: An increasing number of people suffer from neck pain due to life
style and prolonged use of computers. Research has revealed that myofascial
trigger points (MTrPs) and the intramuscular innervation zone (IZ) are involved
in neck pain. MTrPs are induced mainly by IZ dysfunction of the affected skeletal
muscle and the 2 do not overlap in location. The question is whether injection
treatment in MTrPs or in the IZ is more effective to relieve MTrPs-associated
pains. The precise location and body-surface map of the intramuscular IZ in the
trapezius muscle and a clinical injection study in the IZ may provide a useful
answer to the question. OBJECTIVES: This study aimed to investigate the efficacy
of lidocaine injection in the intramuscular IZ for the treatment of chronic neck
pain caused by MTrPs in the trapezius muscle. STUDY DESIGN: Prospective
observational study, approved by the local research ethics. SETTING: University
hospital, departments of Anesthesiology and Anatomy. METHODS: First, for the
determination of IZ distribution and body-surface mapping, a modified
intramuscular Sihler's neural staining technique was applied to elucidate nerve
distribution patterns of the trapezius muscle. Then, 120 patients with myofascial
pain syndrome (MPS) of the trapezius muscle were randomly divided into 5 groups
for analysis. Group 1 (n = 24) received injections of saline (0.9% NaCl) at the
MTrPs. Group 2 (n = 24) received injections of 0.5% lidocaine at the MTrPs. Group
3 (n = 24) received injections of saline (0.9% NaCl) at the mid-upper trapezius
(Point E). Group 4 (n = 24) received injections of 0.5% lidocaine at Point E.
Group 5 (n = 24) received a combined injection of 0.5% lidocaine treatment at
both Point E and the lower trapezius (Point F). The injection dose was 4 mL at
each injection site. All patients received injections once a week for 4 weeks.
The visual analogue scale (VAS) and the frequency of painful days per month (FPD)
were obtained before treatment and at 2, 4, and 6 months after treatment.
RESULTS: The intramuscular terminal nerve branches presented a "dendritic"
distribution in the trapezius muscle and were connected with each other to form
an S-shaped IZ belt in the middle of the muscle belly. Compared with the MTrP
injection group, lidocaine-injection therapy in the IZ significantly reduced the
degree and frequency of neck pain in patients at 6 months after treatment,
especially the combined lidocaine-injection therapy in the IZ of both the mid
upper trapezius and the lower trapezius are more effective (all P < 0.05).
CONCLUSIONS: This study confirms that lidocaine-injection therapy in the IZ
significantly reduces the degree and frequency of neck pain in patients at 6
months after treatment. The combined lidocaine-injection therapy in the IZ of
both the mid-upper trapezius and the lower trapezius is more effective. In
addition, this study establishes a clear distribution map of intramuscular nerves
that will be conducive to the future use of chemical blockers and electrical
stimulation in the nervous system in treating MPS of the trapezius muscle.
LIMITATIONS: The small number of patients and the short duration of follow-up.
PMID- 26431136
TI - Incidence and Demographics of Post-Operative Naloxone Administration: A 13-Year
Experience at a Major Tertiary Teaching Institution.
AB - BACKGROUND: Perioperative use of opioids is associated with the risk of opioid
induced respiratory depression. Naloxone is a competitive opioid antagonist
typically administered to reverse opioid-induced respiratory depression.
Postoperative administration of naloxone may be considered a proxy for
significant postoperative opioid-induced respiratory depression and data
regarding its use may be utilized as a quality measure. Few large studies have
been done to characterize the population and define an incidence of naloxone
recipients in the postoperative inpatient setting. OBJECTIVES: We aimed to
characterize the demographics of patients receiving postoperative naloxone, as
well as the incidence of administration in the first 72 post-operative hours at a
large urban academic medical center in the United States. STUDY DESIGN: This is a
retrospective cohort study. SETTING: Major urban tertiary teaching institution.
METHODS: The robust electronic record database of The Department of
Anesthesiology at The Icahn School of Medicine at Mount Sinai, as well as the
institution's data warehouse were instrumental in allowing almost 450,000
surgical cases performed between 2001 and 2014 to be screened for naloxone
administration within the first 72 postoperative hours. Organ harvests, outside
of OR intubations, cancelled cases, and patients age less than or equal to 18
were excluded from the total case count. RESULTS: Naloxone was administered 433
times in a total of 442,699 postoperative cases. This yielded an incidence of
0.1%. Additionally, the demographics of the group receiving naloxone were
described. The mean age was 60, mean body mass index (BMI) was 27, 60% were
women, and the mean American Society of Anesthesiologists (ASA) status was 3.
Average time to naloxone administration was 21 hours (standard deviation 7) after
surgery. Thirteen percent of the cases were emergent. Breakdown of anesthetic
technique revealed that 81% of the cases were performed under general anesthesia,
7% with monitored anesthesia care (MAC), and 12% under neuraxial anesthesia. This
study lays the groundwork for further elucidating risk factors for postoperative
administration of naloxone. LIMITATIONS: This is a retrospective study.
CONCLUSION: The overall incidence of postoperative naloxone administration over a
13 year period in approximately 450,000 patients was 0.1%. Demographics of this
group were older, ASA 3 women, qualifying as overweight, but not obese,
undergoing elective surgery with a general anesthetic technique. Average time to
administration was 21 hours postoperatively.
PMID- 26431137
TI - Catheter-tip Granulomas Associated with Intrathecal Drug Delivery--A Two-Center
Experience Identifying 13 Cases.
AB - BACKGROUND: Intrathecal (IT) drug therapy with implanted pumps is an effective
treatment modality for chronic pain and/or spasticity, especially after non
invasive treatment has failed. Long-term use of intrathecal opioids may cause
formation of inflammatory masses at the tip of intrathecal catheters, possibly
leading to neurological deficits and/or catheter revision. OBJECTIVE: We aimed to
identify risk factors for catheter-tip granuloma (CG) formation. STUDY DESIGN:
Retrospective study. SETTING: Tertiary Spine Centers in Germany and Switzerland.
METHODS: We retrospectively reviewed data at 2 Swiss centers (Kantonsspital St.
Gallen, Swiss Paraplegic Centre Nottwil) between 01/1994 and 10/2013. Collected
data were age at operation, gender, smoking status, previous spinal operations,
spinal level of catheter-tip, clinical symptoms, catheter testing with contrast
agent, applied drugs, drug concentration, as well as cumulative daily drug
dosages. RESULTS: Thirteen patients with a mean age of 52.6 years and CG
formation after a mean of 6.9 years of follow-up were identified and compared to
54 patients of similar age and length of follow-up (48.6 years, P = 0.535; follow
up 5.3 years, P = 0.236) without CG. In the analysis of risk factors, catheter
ending in the middle thoracic spine (Th4-8; 38.5 vs. 6.5%; P = 0.010), previous
spinal surgery (75 vs. 41%; P = 0.051), and chronic pain as an underlying primary
symptom for IT drug therapy (100 vs. 56%, P = 0.003) were associated with CG
formation. IT drug therapy for spasticity appeared to be much less associated
with CG formation (0 vs. 44%, P = .0003). As the symptomatology is closely
related to the medical treatment applied, patients with CG were more likely to be
treated with IT morphine (77 vs. 20%; P < 0.001), and as tendency with IT
clonidine (54 vs. 26%; P = 0.092) and IT bupivacaine (46 vs. 20%; P = 0.077).
Average in-pump morphine concentration (30.3 vs. 19.5 mg/mL; P = 0.05) as well as
average daily dose of morphine (12.5 vs. 6.2 mg/d; P = 0.037) were significantly
higher in the CG group. Smoking could not be identified as risk factor for CG
formation. LIMITATIONS: Limitations include the retrospective approach, the
limited group size of granuloma patients, as well as missing data in the
investigated patient groups. CONCLUSION: Our patient cohort with CG differed in
some features, of which some like catheter localization, choice, dosage, and the
concentration of drugs are potentially modifiable. These results could contribute
to the prevention of CG in the future.
PMID- 26431138
TI - Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome:
Comorbidity with Fibromyalgia Does Matter.
AB - BACKGROUND: In addition to the frequently reported pain complaints, performance
based cognitive capabilities in patients with chronic fatigue syndrome (CFS) with
and without comorbid fibromyalgia (FM) are significantly worse than those of
healthy controls. In various chronic pain populations, cognitive impairments are
known to be related to pain severity. However, to the best of our knowledge, the
association between cognitive performance and experimental pain measurements has
never been examined in CFS patients. OBJECTIVES: This study aimed to examine the
association between cognitive performance and self-reported as well as
experimental pain measurements in CFS patients with and without FM. STUDY DESIGN:
Observational study. SETTING: The present study took place at the Vrije
Universiteit Brussel and the University of Antwerp. METHODS: Forty-eight (18 CFS
only and 30 CFS+FM) patients and 30 healthy controls were studied. Participants
first completed 3 performance-based cognitive tests designed to assess selective
and sustained attention, cognitive inhibition, and working memory capacity. Seven
days later, experimental pain measurements (pressure pain thresholds [PPT],
temporal summation [TS], and conditioned pain modulation [CPM]) took place and
participants were asked to fill out 3 questionnaires to assess self-reported
pain, fatigue, and depressive symptoms. RESULTS: In the CFS+FM group, the
capacity of pain inhibition was significantly associated with cognitive
inhibition. Self-reported pain was significantly associated with simple reaction
time in CFS-only patients. The CFS+FM but not the CFS-only group showed a
significantly lower PPT and enhanced TS compared with controls. LIMITATIONS: The
cross-sectional nature of this study does not allow for inferences of causation.
CONCLUSIONS: The results underline disease heterogeneity in CFS by indicating
that a measure of endogenous pain inhibition might be a significant predictor of
cognitive functioning in CFS patients with FM, while self-reported pain appears
more appropriate to predict cognitive functioning in CFS patients without FM.
PMID- 26431139
TI - High Prevalence of Hypovitaminosis D in Indian Chronic Low Back Patients.
AB - BACKGROUND: Vitamin D has a significant role to play in bone metabolism and
neuromuscular function. Several researchers have indicated that Vitamin D
deficiency may be possibly related to chronic musculoskeletal pain including
chronic low back pain (CLBP). OBJECTIVES: The present study was conducted to
determine the prevalence of hypovitaminosis D and its contribution to chronic
lower back pain. STUDY DESIGN: Controlled study. SETTING: Outpatient pain clinic
of tertiary care hospital. METHODS: Data presented in this manuscript are from
patients who were screened for inclusion in an open label, single arm clinical
trial aimed to assess the effectiveness of vitamin D supplementation in patients
with CLBP. Consecutive patients visiting the outpatient pain clinic of a tertiary
care hospital with a diagnosis of CLBP with or without leg pain were recruited. A
visual analogue scale (VAS) was used to measure low back pain intensity, and the
Modified Oswestry disability questionnaire (MODQ) was used to measure functional
ability. Plasma 25-OHD levels of all patients were measured and the prevalence of
hypovitaminosis D was calculated. The multivariate logistic regression model was
used to investigate the association between vitamin D deficiency and patient
characteristics. RESULTS: A total of 328 patients were included in the study.
Mean age of the study population was 43.8 years. Two hundred eighty-two (86%)
(men 153/172 [89%], women 129/156 [83%]) of patients had below normal plasma
vitamin D levels. Among these, 217 (66%) (men 126 [73%], women 91 [58%]) were
found to be deficient and 65 (20%) (men 27 [16%], women 38 [24%]) were had
insufficient levels. Multivariate regression analysis found that men were
significantly more prone to have deficiency as compared to women (OR = 1.78 (1.10
2.88), P = 0.02). We also found a significantly positive relationship between
vitamin D deficiency and increased functional disability (OR = 1.53 (1.24-1.87),
P = 0.01). However, we did not find any relationship with pain severity, presence
of other co-morbidities and educational level. LIMITATIONS: Not possible to
access a good quality data on sun exposure and vitamin D dietary inake dieat in
study population. No bone scans were performed. CONCLUSION: The result of this
study provides a message about the high prevalence of hypovitaminosis D in the
Indian CLBP population. Clinical guidelines for managing CLBP should include
assessment of vitamin D status, together with advice on appropriate vitamin D
supplementation in those found to be deficient. CLINICAL TRIAL REGISTRATION:
CTRI/2014/03/004459.
PMID- 26431140
TI - Chronic Pain in the Elderly: The Case for New Therapeutic Strategies.
AB - BACKGROUND: Elderly patients in general exhibit a higher incidence of chronic and
neuropathic pain conditions. This group poses a particular clinical challenge due
to age-related pharmacokinetic and pharmacodynamic issues, comorbid conditions,
and polypharmacy, as well as frailty and cognitive decline. Poor control of pain
has consistently been identified as an issue for older people. The identification
of safe and efficacious treatments for chronic pain remains a critical public
health concern, especially considering the progressive increase of the world's
elderly population. OBJECTIVES: This narrative review deals with the principal
alterations of the somatosensory system together with changes in non-neuronal
cells in the course of aging. The possibility to control chronic pain based on an
innovative strategy which addresses non-neuronal cell dysregulation control will
also be discussed. STUDY DESIGN: Narrative review. RESULTS: Peripheral nerves
display functional, structural, and biochemical changes with aging that mainly
involve Adelta fibers. Alteration in the responses to heat pain in the middle
insular cortex and primary somatosensory cortex are also observed in the elderly.
In general, pain threshold increases with age while the threshold of pain
tolerance remains unchanged or decreases. Additionally, other important
modifications of the pain perception system in this age group consist in a clear
reduction in the descending inhibitory capacity with an associated increase in
central sensitization. Furthermore, different changes concern immune system
cells, such as mast cells and microglia, that with age show an increase in their
sensitivity to noxious stimuli and a decreased capability to be regulated by
homeostatic endogenous systems. Since these cells are the primary interlocutors
for pain neurons, their alterations lead to changes that promote persistent
neuroinflammation, thereby impacting pain neuronal cell functionality.
LIMITATION: This review is not an exhaustive review for the current evidence
supporting the role of immune cells in influencing pain somatosensory neuron
functions. It is also important to stress the small number of studies designed to
determine the efficacy and safety of anti-pain therapies in elderly patients.
CONCLUSION: Non-neuronal cells of immune system origin such as microglia and mast
cells, along with astrocytes, are capable of influencing pain somatosensory
neuron functions. These nervous system non-neuronal cells may thus be viewed as
innovative targets for persistent pain control. Among therapies aiming at
preserving the functionality of non-neuronal cells, palmitoylethanolamide, with
its high efficacy/risk ratio, may be an excellent co-treatment for the ever
growing elderly population with chronic pain.
PMID- 26431141
TI - Is Serum Hypovitaminosis D Associated with Chronic Widespread Pain Including
Fibromyalgia? A Meta-analysis of Observational Studies.
AB - BACKGROUND: Chronic widespread pain (CWP) is a global musculoskeletal disorder
leading to disability and a reduced quality of life. Low levels of serum vitamin
D has long been proposed to be associated with CWP, but previous research remains
inconclusive. OBJECTIVES: To determine whether hypovitaminosis D was
independently associated with CWP. STUDY DESIGN: Meta-analysis of observational
study. METHODS: Electronic databases were searched for studies published up to
November 2014 comparing the prevalence of hypovitaminosis D and serum vitamin D
levels between participants with and without CWP. The crude and adjusted odds
ratios (ORs) of hypovitaminosis D with CWP were calculated. Subgroup analysis
according to gender, threshold of hypovitaminosis, and definition of patients was
performed, as well as meta-regression to test the linear relationship between
crude ORs and the latitude of study locations. RESULTS: Twelve studies were
included, comprising 1,854 patients with CWP. The patient group showed a
significantly higher risk of hypovitaminosis D than the control group (crude OR,
1.63; 95% CI, 1.20-2.23). The association was slightly attenuated after adjusting
confounders, with a pooled adjusted OR of 1.41 (95% CI, 1.00-2.00). There was an
increase in ORs of hypovitaminosis D using a lower diagnostic value of serum
vitamin D (8 and 10 ng/mL). The subgroup analysis according to gender and
definition of CWP did not reveal significant between-group differences. The meta
regression showed no linear relationship between latitude and the crude ORs.
CONCLUSIONS: There was a positive crude association between hypovitaminosis D and
CWP, and the association was likely to remain after adjusting confounding
factors. Use of a cut-off value of hypovitaminosis D (8-10 ng/mL) could better
define the population with and without CWP. Further prospective follow-up studies
are warranted to clarify the causal relationship between hypovitaminosis D and
CWP.
PMID- 26431142
TI - Prevalence of Neuropathic Pain in Patients Scheduled for Lumbar Spine Surgery:
Nationwide, Multicenter, Prospective Study.
AB - BACKGROUND: There is limited evidence about surgical outcomes after lumbar spinal
surgery in patients with neuropathic pain (NP) or the prevalence of NP
proportions among patients with degenerative lumbar diseases who are candidates
for a surgical interventions. OBJECTIVE: The objectives of this study were to
investigate the prevalence of NP among patients scheduled for lumbar spinal
surgery and the relationship between health-related quality of life (HRQoL) and
NP. This study also aimed to identify the risk factors related to NP and compare
the clinical outcomes after surgical treatment between patients with and without
NP. STUDY DESIGN: This study was a nationwide, multicenter, prospective, and
observational study. It was conducted from Sep-Oct 2011 to May 2013, and included
a total of 1,109 patients who were scheduled for lumbar spinal surgery from 44
spinal centers (both orthopedics and neurosurgeons). SETTING: Multicenter study.
METHODS: Patients were diagnosed of having NP if the Leeds Assessment of
Neuropathic Symptoms and Signs (LANSS) pain scale was = 12 points. The patients
were investigated to assess the differences in their clinical outcomes one week
and 3 months after surgery and were followed-up with regards to pain and HRQoL to
explore the risk factors affecting NP. RESULTS: Of 1,109 recruited patients, 404
(36.4%) suffered from NP (mean age 62.06 years; 37.9% men) with mean LANSS score
of 17.44 +/- 4.06, while 705 (63.6%) had nociceptive pain with mean LANSS score
of 6.03 +/- 3.52. At baseline, patients with NP showed lower HRQoL and more
severe pain compared to nociceptive pain patients. However, 3 months after
surgical treatment, the NP group showed greater improvement in pain NRS (P =
0.087) and EQ-5D (P = 0.029) as compared to nociceptive pain group. Longer
symptom duration was identified as a risk factor for NP (OR 1.003, respectively,
P = 0.020). CONCLUSION: There was a high prevalence of NP in Korean patients
scheduled for lumbar spine surgery, and these patients suffered greater pain and
lower HRQoL than nociceptive pain patients. The more remarkable improvement NP
patients showed after treatment highlights the importance of appropriate
diagnosis and treatment of NP.
PMID- 26431143
TI - Accuracy of Ultrasound-Guided Genicular Nerve Block: A Cadaveric Study.
AB - BACKGROUND: Genicular nerve block has recently emerged as a novel alternative
treatment in chronic knee pain. The needle placement for genicular nerve
injection is made under fluoroscopic guidance with reference to bony landmarks.
OBJECTIVE: To investigate the anatomic landmarks for medial genicular nerve
branches and to determine the accuracy of ultrasound-guided genicular nerve block
in a cadaveric model. STUDY DESIGN: Cadaveric accuracy study. SETTING: University
hospital anatomy laboratory. METHODS: Ten cadaveric knee specimens without
surgery or major procedures were used in the study. The anatomic location of the
superior medial genicular nerve (SMGN) and the inferior medial genicular nerve
(IMGN) was examined using 4 knee dissections. The determined anatomical sites of
the genicular nerves in the remaining 6 knee specimens were injected with 0.5 mL
red ink under ultrasound guidance. The knee specimens were subsequently dissected
to assess for accuracy. If the nerve was dyed with red ink, it was considered
accurate placement. All other locations were considered inaccurate. RESULTS: The
course of the SMGN is that it curves around the femur shaft and passes between
the adductor magnus tendon and the femoral medial epicondyle, then descends
approximately one cm anterior to the adductor tubercle. The IMGN is situated
horizontally around the tibial medial epicondyle and passes beneath the medial
collateral ligament at the midpoint between the tibial medial epicondyle and the
tibial insertion of the medial collateral ligament. The adductor tubercle for the
SMGN and the medial collateral ligament for the IMGN were determined as anatomic
landmarks for ultrasound. The bony cortex one cm anterior to the peak of the
adductor tubercle and the bony cortex at the midpoint between the peak of the
tibial medial epicondyle and the initial fibers inserting on the tibia of the
medial collateral ligament were the target points for the injections of SMGN and
IMGN, respectively. In the cadaver dissections both genicular nerves were seen to
be dyed with red ink in all the injections of the 6 knees. LIMITATIONS: The small
number of cadavers might have led to some anatomic variations of genicular nerves
being overlooked. CONCLUSIONS: The result of this cadaveric study suggests that
ultrasound-guided medial genicular nerve branch block can be performed accurately
using the above-stated anatomic landmarks.
PMID- 26431144
TI - Successful Spinal Cord Stimulator Trial and Permanent Implant in Patient with
Diabetic Peripheral Neuropathy on Chronic Dual Antiplatelet Therapy.
AB - The safety of neuraxial anesthetic techniques in the setting of oral and
parenteral anticoagulation is an area of growing interest and clinical inquiry as
the multitude of anticoagulant medications rapidly increases. Additionally, the
indications for spinal cord stimulation therapy are evolving as both technique
and technology in the field continue to advance. The estimated incidence of
spinal hematoma following epidural injection has been estimated to be 1 in
150,000-200,000. However, there is very little data on the risk of indwelling
spinal cord simulation leads and chronic use of anticoagulant medications. We
would like to report a recent case for consideration in which a spinal cord
stimulator trial was successful and led to permanent spinal cord stimulator
implantation in a patient with diabetic peripheral neuropathy taking life-long
aspirin and clopidogrel therapy secondary to extensive coronary and carotid
atherosclerosis. The report serves as a novel case to encourage exploration into
the topic of anticoagulation therapy with indwelling spinal cord stimulator
leads. The case brings up a number of critical questions that cannot clearly be
answered with the current literature and some interesting topics for discussion
including the need for acute systemic anticoagulation in the future for vascular
interventions and risk stratification for those patients selected for spinal cord
stimulation.
PMID- 26431145
TI - Lumbar Sympathetic Block with Botulinum Toxin Type B for Complex Regional Pain
Syndrome: A Case Study.
AB - Lumbar sympathetic block (LSB) is an effective method for relief of
sympathetically mediated pain in the lower extremities. To prolong the
sympathetic blockade, sympathetic destruction with alcohol or radiofrequency has
been used. The pre-ganglionic sympathetic nerves are cholinergic, and botulinum
toxin (BTX) has been found to inhibit the release of acetylcholine at the
cholinergic nerve terminals. Moreover, BTX type B (BTX-B) is more convenient to
use than BTX type A. Based on these findings, we performed LSB on the 2 patients
with complex regional pain syndrome (CRPS) in the lower extremity.
Levobupivacaine 0.25% 5 mL mixed with BTX-B 5,000 IU was given under fluoroscopic
guidance. Two months after LSB with BTX-B, pain intensity and the Leeds
assessment of neuropathic symptoms and signs (LANSS) score were significantly
reduced. Allodynia and coldness disappeared and skin color came back to normal.
In conclusion, BTX-B can produce an efficacious and durable sympathetic blocking
effect on patients with CRPS.
PMID- 26431146
TI - Brachial Plexus Block for Cancer-Related Pain: A Case Series.
AB - Neoplastic brachial plexopathy (NBP) is caused by a cancerous infiltration into
the brachial plexus, presenting often as severe pain in the affected upper
extremity. Such pain can be resistant to medical treatment. Invasive
interventions such as brachial plexus neurolysis with phenol or cordotomy may
result in severe complications including permanent neurological damage and death.
Continuous brachial plexus and paravertebral block with local anesthetic have
been reported to successfully control pain from NBP, but these techniques are
logistically challenging and frequently have catheter-related complications. We
report a series of patients who received single-shot brachial plexus blocks with
a mixture of local anesthetic and corticosteroid (bupivacaine 0.25% with methyl
prednisolone 20-120 mg) for the treatment of refractory cancer-related pain in
the brachial plexus territory, mostly from NBP. Theoretically, such blocks could
provide immediate analgesia from the local anesthetic and a longer-lasting
analgesia from the slow-release steroids. Responders reported a sustained
decrease in their pain (lasting from 2 weeks to 10 months), a significant
decrease in their opioid and non-opioid (ketamine, gabapentin) consumption,
overall satisfaction with the block, and unchanged or improved function of their
limb. The ideal candidate for this procedure is a patient who has pain that is
predominantly neuropathic from a lesion within the brachial plexus and with
anatomy amenable to ultrasound-guided nerve block. Our case series suggests that,
in the appropriately selected patient, this technique can safely and effectively
alleviate pain from NBP. The procedure is simple, spares limb function, and can
be diagnostic, predicting response to more complex procedures. To the best of our
knowledge, this is the first report using this technique for NBP.
PMID- 26431147
TI - Sacral Insufficiency Fracture: An Insidious Cause for Low Back Pain.
PMID- 26431148
TI - Treatment of Abdominal Segmental Hernia, Constipation, and Pain Following Herpes
Zoster with Paravertebral Block.
AB - Herpes zoster (HZ) most commonly occurs in elderly patients and involves sensory
neurons resulting in pain and sensory changes. Clinically significant motor
deficits and visceral neuropathies are thought to be relatively rare. A 72-year
old man presented with abdominal segmental hernia, constipation, and pain
following HZ in the left T9-10 dermatome. Sixteen days before presentation, he
had developed a painful herpetic rash in the left upper abdominal quadrant.
Approximately 10 days after the onset of the rash, constipation occurred and was
managed with daily oral medication with bisacodyl 5 mg. In addition, 14 days
after the onset of HZ, the patient noticed a protrusion of the left upper
abdominal wall. Abdominal x-ray, ultrasound of the abdomen, and electrolyte
analysis showed no abnormalities. General physical examination revealed a
reducible bulge in his left upper quadrant and superficial abdominal reflexes
were diminished in the affected region. Electromyographic testing revealed
denervational changes limited to the left thoracic paraspinal muscles and
supraumbilical muscles, corresponding to the affected dermatomes. He was
prescribed with 500 mg of famciclovir 3 times a day for 7 days, and pregabalin 75
mg twice a day and acetaminophen 650 mg 3 times a day for 14 days. However, his
pain was rated at an intensity of 5 on the numerical analogue scale from 0 (no
pain) to 10 (worst pain imaginable). A paravertebral block was performed at T9-10
with a mixture of 0.5% lidocaine 3 mL and triamcinolone 40 mg. One day after the
procedure, the abdominal pain disappeared. In addition, 5 days after the
intervention, the abdominal protrusion and constipation were resolved. He
currently remains symptom free at a 6 month follow-up.
PMID- 26431149
TI - "Bursitis De Novo": A Clinical Case of Ischiofemoral Impingement.
PMID- 26431150
TI - Landmark of Ultrasound-Guided Trigeminal Block: Lateral Pterygoid Muscle.
PMID- 26431151
TI - Response.
PMID- 26431152
TI - Pain Relief Following Shoulder Arthroscopy In Patients Receiving Preoperative
Stellate Ganglion Block--Some More Facts!
PMID- 26431153
TI - Description of Optimal Angle of Needle Insertion For L5 Transforaminal Epidural
Injection Leads to Complications.
PMID- 26431154
TI - Development of a Phase-Transfer-Catalyzed, [2,3]-Wittig Rearrangement.
AB - An investigation into the use of phase-transfer catalysis for the [2,3]
sigmatropic rearrangement of allyloxy carbonyl compounds is described. Initial
studies focused on identifying viable substrate classes that would undergo
selective [2,3]-rearrangement under phase-transfer catalysis. Under certain
conditions, the [2,3]-sigmatropic rearrangement of allyloxy carbonyl compounds
takes place in the presence of a phase-transfer agent, providing a rare example
of a phase-transfer-catalyzed unimolecular reaction. In the course of this
investigation, it was found that catalysis is dependent on several variables
including base concentration, catalyst structure, and substrate lipophilicity.
Preliminary testing of chiral, nonracemic phase-transfer catalysts has shown
promising levels of enantioselectivity for future development.
PMID- 26431155
TI - MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis
and/or Cholangiocarcinoma.
AB - BACKGROUND AND AIM: Patients with primary sclerosing cholangitis (PSC) are at
high risk for the development of cholangiocarcinoma (CC). Analysis of micro
ribonucleic acid (MiRNA) patterns is an evolving research field in biliary
pathophysiology with potential value in diagnosis and therapy. Our aim was to
evaluate miRNA patterns in serum and bile of patients with PSC and/or CC.
METHODS: Serum and bile from consecutive patients with PSC (n = 40 (serum), n =
52 (bile)), CC (n = 31 (serum), n = 19 (bile)) and patients with CC complicating
PSC (PSC/CC) (n = 12 (bile)) were analyzed in a cross-sectional study between
2009 and 2012. As additional control serum samples from healthy individuals were
analyzed (n = 12). The miRNA levels in serum and bile were determined with global
miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated
validation. RESULTS: Serum analysis revealed significant differences for miR-1281
(p = 0.001), miR-126 (p = 0.001), miR-26a (p = 0.001), miR-30b (p = 0.001) and
miR-122 (p = 0.034) between patients with PSC and patients with CC. All validated
miRNAs were significantly lower in healthy individuals. MiR-412 (p = 0.001), miR
640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) were significantly
different between patients with PSC and PSC/CC in bile. CONCLUSIONS: Patients
with PSC and/or CC have distinct miRNA profiles in serum and bile. Furthermore,
miRNA concentrations are different in bile of patients with CC on top of PSC
indicating the potential diagnostic value of these miRNAs.
PMID- 26431157
TI - Insights into Structure-Activity Relationships of Bacterial RNA Polymerase
Inhibiting Corallopyronin Derivatives.
AB - The new compound precorallopyronin A is a stable precursor in the biosynthesis of
the antibiotic corallopyronin A. This natural product was isolated from the
producer strain Corallococcus coralloides B035. Together with various
semisynthetically obtained corallopyronin A derivatives its antibacterial effects
were evaluated. In combination with an X-ray crystallization model limitations of
derivatization possibilities were revealed. The antibiotic potential of the novel
precorallopyronin A is comparable to that of the structurally more complex
corallopyronin A, which highlights that the additional chiral center is not
essential for activity.
PMID- 26431158
TI - Reduction in Renal Ischemia-Reperfusion Injury in Mice by a Phosphoinositide 3
Kinase p110gamma-Specific Inhibitor.
AB - BACKGROUND: Although renal ischemia-reperfusion injury (IRI) can cause delayed
graft function, a targeted therapy is not yet available. Because phosphoinositide
3-kinases (PI3K) p110gamma and p110delta play important roles in immune cell
migration and function, we investigated the effects of PI3K p110gamma- and
p110delta-specific inhibitors in a murine renal IRI model. METHODS: Renal
function was assessed by serum creatine and hematoxylin-eosin staining. Immune
cell migration was assessed by flow cytometry and an in vitro cell migration
assay using Transwell plates. Gene expression analysis and a multiplex
cytokine/chemokine assay were performed to find cytokines/chemokines whose
expression was upregulated in renal IRI and affected by p110gamma-specific
inhibitor. RESULTS: The PI3K p110gamma-specific inhibitor, but not p110delta
specific inhibitor, significantly reduced serum creatine levels and acute tubular
necrosis. These were accompanied by reduced infiltration of B cells and reduced
expression of CXCL9, a CXCR3 ligand, suggesting that p110gamma plays an important
role in B-cell migration toward injured kidneys. An in vitro cell migration assay
revealed for the first time that B-cell migration to injured kidney cells and to
CXCL9 requires p110gamma. CONCLUSIONS: p110gamma-specific inhibitor ameliorates
renal IRI by reducing necrosis and immune cell migration. This inhibitor may have
the potential to reduce renal graft failure caused by renal IRI.
PMID- 26431156
TI - Interferon Lambda 4 Genotype Is Not Associated with Recurrence of Oral or Genital
Herpes.
AB - IFNL4-DeltaG/TT (rs368234815) genotype is associated with hepatitis C virus
clearance and may play a role in other infections. IFN-lambda4 protein is
generated only in individuals who carry the IFNL4-DeltaG allele. The IFNL4
rs12979860-T allele, which is in strong linkage disequilibrium with IFNL4-DeltaG,
was recently reported to be associated with more frequent and severe oral herpes
episodes. We investigated the association of IFNL4-DeltaG/TT with herpes simplex
virus (HSV)-related outcomes among 2,192 African American and European American
participants in the Women's Interagency HIV Study (WIHS). WIHS is a prospective
cohort study of human immunodeficiency virus (HIV)-infected and at-risk women
that began in 1994. This report includes follow-up through 2013. Available data
included: HSV-1 and HSV-2 antibodies at study entry; bi-annually ascertained
episodes of (self-reported) oral herpes, (self-reported) genital sores and
(clinician-observed) genital ulcers; HSV-2 DNA in cervicovaginal lavage (CVL)
specimens. IFNL4-DeltaG/TT genotyping was determined by TaqMan. We compared women
with IFNL4-DeltaG/DeltaG or IFNL4-TT/DeltaG genotypes (i.e., IFNL4-DeltaG
carriers) to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV
status. For outcomes with repeated measurements, the adjusted odds ratio (aOR),
95% confidence interval [CI] and p-value were determined using a generalized
estimating equations approach. Median participant age at enrollment was 36 years;
81% were African American, 74% were HIV-infected. Among 1,431 participants tested
for antibodies, 72.8% were positive for HSV-1 and 79.0% were positive for HSV-2.
We observed no association between IFNL4-DeltaG/TT genotype and any outcome: HSV
1 or HSV-2 antibody prevalence (p>0.1, all comparisons); oral herpes (aOR, 1.2; p
= 0.35); genital sores (aOR, 1.0; p = 0.71); genital ulcers (aOR, 1.1; p = 0.53);
detectable HSV-2 DNA in CVL (N = 322; aOR, 0.71; p = 0.49); HSV-2 DNA level (p =
0.68). In this large prospective study, IFNL4-DeltaG/TT genotype was not
associated with HSV-related outcomes, including episodes of oral or genital
herpes.
PMID- 26431159
TI - Osteogenesis Imperfecta Associated with Dendriform Pulmonary Ossification.
PMID- 26431160
TI - NTHL1 defines novel cancer syndrome.
PMID- 26431161
TI - HSP60: a double edge sword in autoimmunity.
PMID- 26431162
TI - Synergistic effects of p53 activation via MDM2 inhibition in combination with
inhibition of Bcl-2 or Bcr-Abl in CD34+ proliferating and quiescent chronic
myeloid leukemia blast crisis cells.
AB - The Bcr-Abl tyrosine kinase regulates several Bcl-2 family proteins that confer
resistance to apoptosis in chronic myeloid leukemia (CML) cells. Given p53's
ability to modulate the expression and activity of Bcl-2 family members, we
hypothesized that targeting Bcr-Abl, Bcl-2, and p53 concomitantly could have
therapeutic benefits in blast crisis (BC) CML and in quiescent CML CD34+ cells
that are insensitive to tyrosine kinase inhibitors (TKI). We examined the effects
of the MDM2 inhibitor nutlin3a and its combination with the dual Bcl-2 and Bcl-xL
inhibitor ABT-737, and the Bcr-Abl inhibitor nilotinib on BC CML patient samples.
We found that in quiescent CD34+ progenitors, p53 expression is significantly
lower, and MDM2 is higher, compared to their proliferating counterparts.
Treatment with nutlin3a induced apoptosis in bulk and CD34+CD38- cells, and in
both proliferating and quiescent CD34+ progenitor CML cells. Nutlin3a synergized
with ABT-737 and nilotinib, in part by inducing pro-apoptotic, and suppressing
anti-apoptotic, Bcl-2 proteins. Nilotinib inhibited the expression of Bcl-xL and
Mcl-1 in BC CML cells. These results demonstrate that p53 activation by MDM2
blockade can sensitize BC CML cells, including quiescent CD34+ cells, to Bcl-2
inhibitor- and TKI-induced apoptosis. This novel strategy could be useful in the
therapy of BC CML.
PMID- 26431163
TI - Mdm2 inhibition confers protection of p53-proficient cells from the cytotoxic
effects of Wee1 inhibitors.
AB - Pharmacological inhibition of the cell cycle regulatory kinase Wee1 represents a
promising strategy to eliminate cancer cells. Wee1 inhibitors cooperate with
chemotherapeutics, e. g. nucleoside analogues, pushing malignant cells from S
phase towards premature mitosis and death. However, considerable toxicities are
observed in preclinical and clinical trials. A high proportion of tumor cells can
be distinguished from all other cells of a patient's body by inactivating
mutations in the tumor suppressor p53. Here we set out to develop an approach for
the selective protection of p53-proficient cells against the cytotoxic effects of
Wee1 inhibitors. We pretreated such cells with Nutlin-3a, a prototype inhibitor
of the p53-antagonist Mdm2. The resulting transient cell cycle arrest effectively
increased the survival of cells that were subsequently treated with combinations
of the Wee1 inhibitor MK-1775 and/or the nucleoside analogue gemcitabine. In this
constellation, Nutlin-3a reduced caspase activation and diminished the
phosphorylation of Histone 2AX, an indicator of the DNA damage response. Both
effects were strictly dependent on the presence of p53. Moreover, Nutlin pre
treatment reduced the fraction of cells that were undergoing premature mitosis in
response to Wee1 inhibition. We conclude that the pre-activation of p53 through
Mdm2 antagonists serves as a viable option to selectively protect p53-proficient
cells against the cytotoxic effects of Wee1 inhibitors, especially when combined
with a nucleoside analogue. Thus, Mdm2 antagonists might prove useful to avoid
unwanted side effects of Wee1 inhibitors. On the other hand, when a tumor
contains wild type p53, care should be taken not to induce its activity before
applying Wee1 inhibitors.
PMID- 26431166
TI - Nanoscale Electrostructural Characterization of Compositionally Graded Al(x)Ga(1
x)N Heterostructures on GaN/Sapphire (0001) Substrate.
AB - We report on AlxGa1-xN heterostructures resulting from the coherent growth of a
positive then a negative gradient of the Al concentration on a [0001]-oriented
GaN substrate. These polarization-doped p-n junction structures were
characterized at the nanoscale by a combination of averaging as well as depth
resolved experimental techniques including: cross-sectional transmission electron
microscopy, high-resolution X-ray diffraction, Rutherford backscattering
spectrometry, and scanning probe microscopy. We observed that a small miscut in
the substrate orientation along with the accumulated strain during growth led to
a change in the mosaic structure of the AlxGa1-xN film, resulting in the
formation of macrosteps on the surface. Moreover, we found a lateral modulation
of charge carriers on the surface which were directly correlated with these
steps. Finally, using nanoscale probes of the charge density in cross sections of
the samples, we have directly measured, semiquantitatively, both n- and p-type
polarization doping resulting from the gradient concentration of the AlxGa1-xN
layers.
PMID- 26431165
TI - RAGE mediated intracellular Abeta uptake contributes to the breakdown of tight
junction in retinal pigment epithelium.
AB - Intracellular amyloid beta (Abeta) has been implicated in neuronal cell death in
Alzheimer's disease (AD). Intracellular Abeta also contributes to tight junction
breakdown of retinal pigment epithelium (RPE) in age-related macular degeneration
(AMD). Although Abeta is predominantly secreted from neuronal cells, the
mechanism of Abeta transport into RPE remains to be fully elucidated. In this
study, we demonstrated that intracellular Abeta was found concomitantly with the
breakdown of tight junction in RPE after subretinal injection of Abeta into the
mouse eye. We also presented evidence that receptor for advanced glycation end
products (RAGE) contributed to endocytosis of Abeta in RPE. siRNA-mediated
knockdown of RAGE prevented intracellular Abeta accumulation as well as
subsequent tight junction breakdown in RPE. In addition, we found that RAGE
mediated p38 MAPK signaling contributed to endocytosis of Abeta. Blockade of
RAGE/p38 MAPK signaling inhibited Abeta endocytosis, thereby preventing tight
junction breakdown in RPE. These results implicate that intracellular Abeta
contributes to the breakdown of tight junction in RPE via the RAGE/p38 MAPK
mediated endocytosis. Thus, we suggest that RAGE could be a potential therapeutic
target for intracellular Abeta induced outer BRB breakdown in AMD.
PMID- 26431164
TI - The dark side of ZNF217, a key regulator of tumorigenesis with powerful biomarker
value.
AB - The recently described oncogene ZNF217 belongs to a chromosomal region that is
frequently amplified in human cancers. Recent findings have revealed that
alternative mechanisms such as epigenetic regulation also govern the expression
of the encoded ZNF217 protein. Newly discovered molecular functions of ZNF217
indicate that it orchestrates complex intracellular circuits as a new key
regulator of tumorigenesis. In this review, we focus on recent research on ZNF217
driven molecular functions in human cancers, revisiting major hallmarks of cancer
and highlighting the downstream molecular targets and signaling pathways of
ZNF217. We also discuss the exciting translational medicine investigating ZNF217
expression levels as a new powerful biomarker, and ZNF217 as a candidate target
for future anti-cancer therapies.
PMID- 26431172
TI - Correction: Advantages of Task-Specific Multi-Objective Optimisation in
Evolutionary Robotics.
PMID- 26431171
TI - Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee,
Apis mellifera.
AB - The number of honey bee colonies in the United States has declined to half of its
peak level in the 1940s, and colonies lost over the winter have reached levels
that are becoming economically unstable. While the causes of these losses are
numerous and the interaction between them is very complex, the role of
insecticides has garnered much attention. As a result, there is a need to better
understand the risk of insecticides to bees, leading to more studies on both
toxicity and exposure. While much research has been conducted on insecticides and
bees, there have been very limited studies to elucidate the role that bee
genotype and age has on the toxicity of these insecticides. The goal of this
study was to determine if there are differences in insecticide sensitivity
between honey bees of different genetic backgrounds (Carniolan, Italian, and
Russian stocks) and assess if insecticide sensitivity varies with age. We found
that Italian bees were the most sensitive of these stocks to insecticides, but
variation was largely dependent on the class of insecticide tested. There were
almost no differences in organophosphate bioassays between honey bee stocks (<1
fold), moderate differences in pyrethroid bioassays (1.5 to 3-fold), and dramatic
differences in neonicotinoid bioassays (3.4 to 33.3-fold). Synergism bioassays
with piperonyl butoxide, amitraz, and coumaphos showed increased phenothrin
sensitivity in all stocks and also demonstrated further physiological differences
between stocks. In addition, as bees aged, the sensitivity to phenothrin
significantly decreased, but the sensitivity to naled significantly increased.
These results demonstrate the variation arising from the genetic background and
physiological transitions in honey bees as they age. This information can be used
to determine risk assessment, as well as establishing baseline data for future
comparisons to explain the variation in toxicity differences for honey bees
reported in the literature.
PMID- 26431173
TI - Anthropogenically-Mediated Density Dependence in a Declining Farmland Bird.
AB - Land management intrinsically influences the distribution of animals and can
consequently alter the potential for density-dependent processes to act within
populations. For declining species, high densities of breeding territories are
typically considered to represent productive populations. However, as density
dependent effects of food limitation or predator pressure may occur (especially
when species are dependent upon separate nesting and foraging habitats), high
territory density may limit per-capita productivity. Here, we use a declining but
widespread European farmland bird, the yellowhammer Emberiza citrinella L., as a
model system to test whether higher territory densities result in lower fledging
success, parental provisioning rates or nestling growth rates compared to lower
densities. Organic landscapes held higher territory densities, but nests on
organic farms fledged fewer nestlings, translating to a 5 times higher rate of
population shrinkage on organic farms compared to conventional. In addition, when
parental provisioning behaviour was not restricted by predation risk (i.e., at
times of low corvid activity), nestling provisioning rates were higher at lower
territory densities, resulting in a much greater increase in nestling mass in low
density areas, suggesting that food limitation occurred at high densities. These
findings in turn suggest an ecological trap, whereby preferred nesting habitat
does not provide sufficient food for rearing nestlings at high population
density, creating a population sink. Habitat management for farmland birds should
focus not simply on creating a high nesting density, but also on ensuring
heterogeneous habitats to provide food resources in close proximity to nesting
birds, even if this occurs through potentially restricting overall nest density
but increasing population-level breeding success.
PMID- 26431174
TI - Prediction of Neurological Impairment in Cervical Spondylotic Myelopathy using a
Combination of Diffusion MRI and Proton MR Spectroscopy.
AB - PURPOSE: In the present study we investigated a combination of diffusion tensor
imaging (DTI) and magnetic resonance spectroscopic (MRS) biomarkers in order to
predict neurological impairment in patients with cervical spondylosis. METHODS:
Twenty-seven patients with cervical spondylosis were evaluated. DTI and single
voxel MRS were performed in the cervical cord. N-acetylaspartate (NAA) and
choline (Cho) metabolite concentration ratios with respect to creatine were
quantified, as well as the ratio of choline to NAA. The modified mJOA scale was
used as a measure of neurologic deficit. Linear regression was performed between
DTI and MRS parameters and mJOA scores. Significant predictors from linear
regression were used in a multiple linear regression model in order to improve
prediction of mJOA. Parameters that did not add value to model performance were
removed, then an optimized multiparametric model was established to predict mJOA.
RESULTS: Significant correlations were observed between the Torg-Pavlov ratio and
FA (R2 = 0.2021, P = 0.019); DTI fiber tract density and FA, MD, Cho/NAA (R2 =
0.3412, P = 0.0014; R2 = 0.2112, P = 0.016; and R2 = 0.2352, P = 0.010
respectively); along with FA and Cho/NAA (R2 = 0.1695, P = 0.033). DTI fiber
tract density, MD and FA at the site of compression, along with Cho/NAA at C2,
were significantly correlated with mJOA score (R2 = 0.05939, P < 0.0001; R2 =
0.4739, P < 0.0001; R2 = 0.7034, P < 0.0001; R2 = 0.4649, P < 0.0001). A
combination biomarker consisting of DTI fiber tract density, MD, and Cho/NAA
showed the best prediction of mJOA (R2 = 0.8274, P<0.0001), with post-hoc tests
suggesting fiber tract density, MD, and Cho/NAA were all significant contributors
to predicting mJOA (P = 0.00053, P = 0.00085, and P = 0.0019, respectively).
CONCLUSION: A linear combination of DTI and MRS measurements within the cervical
spinal cord may be useful for accurately predicting neurological deficits in
patients with cervical spondylosis. Additional studies may be necessary to
validate these observations.
PMID- 26431175
TI - Host-Associated Metagenomics: A Guide to Generating Infectious RNA Viromes.
AB - BACKGROUND: Metagenomic analyses have been widely used in the last decade to
describe viral communities in various environments or to identify the etiology of
human, animal, and plant pathologies. Here, we present a simple and standardized
protocol that allows for the purification and sequencing of RNA viromes from
complex biological samples with an important reduction of host DNA and RNA
contaminants, while preserving the infectivity of viral particles. PRINCIPAL
FINDINGS: We evaluated different viral purification steps, random reverse
transcriptions and sequence-independent amplifications of a pool of
representative RNA viruses. Viruses remained infectious after the purification
process. We then validated the protocol by sequencing the RNA virome of human
body lice engorged in vitro with artificially contaminated human blood. The full
genomes of the most abundant viruses absorbed by the lice during the blood meal
were successfully sequenced. Interestingly, random amplifications differed in the
genome coverage of segmented RNA viruses. Moreover, the majority of reads were
taxonomically identified, and only 7-15% of all reads were classified as
"unknown", depending on the random amplification method. CONCLUSION: The protocol
reported here could easily be applied to generate RNA viral metagenomes from
complex biological samples of different origins. Our protocol allows further
virological characterizations of the described viral communities because it
preserves the infectivity of viral particles and allows for the isolation of
viruses.
PMID- 26431177
TI - Fat Chance for Neural Stem Cells in Alzheimer's Disease.
AB - Identifying factors driving neural stem cell dysfunction in age-related
neurodegenerative diseases remains critical for the development of potential
regenerative therapies. Now in Cell Stem Cell,Hamilton et al. (2015) find that
lipid accumulation observed during early stages of Alzheimer's disease impairs
neural stem cell activity in the adult brain.
PMID- 26431176
TI - Cellular Expression of Cyclooxygenase, Aromatase, Adipokines, Inflammation and
Cell Proliferation Markers in Breast Cancer Specimen.
AB - Current evidences suggest that expression of Ki67, cyclooxygenase (COX),
aromatase, adipokines, prostaglandins, free radicals, beta-catenin and alpha-SMA
might be involved in breast cancer pathogenesis. The main objective of this study
was to compare expression/localization of these potential compounds in breast
cancer tissues with tissues collected adjacent to the tumor using
immunohistochemistry and correlated with clinical pathology. The breast cancer
specimens were collected from 30 women aged between 49 and 89 years who underwent
breast surgery following cancer diagnosis. Expression levels of molecules by
different stainings were graded as a score on a scale based upon staining
intensity and proportion of positive cells/area or individually. AdipoR1,
adiponectin, Ob-R, leptin, COX-1, COX-2, aromatase, PGF2alpha, F2-isoprostanes
and alpha-SMA were localised on higher levels in the breast tissues adjacent to
the tumor compared to tumor specimens when considering either score or staining
area whereas COX-2 and AdipoR2 were found to be higher considering staining
intensity and Ki67 on score level in the tumor tissue. There was no significant
difference observed on beta-catenin either on score nor on staining area and
intensity between tissues adjacent to the tumor and tumor tissues. A positive
correlation was found between COX-1 and COX-2 in the tumor tissues. In
conclusion, these suggest that Ki67, COXs, aromatase, prostaglandin, free
radicals, adipokines, beta-catenin and alpha-SMA are involved in breast cancer.
These further focus the need of examination of tissues adjacent to tumor, tumor
itself and compare them with normal or benign breast tissues for a better
understanding of breast cancer pathology and future evaluation of therapeutic
benefit.
PMID- 26431178
TI - Moving Toward the Ground State.
AB - Transferring mouse ESCs to a media supplemented with Mek and Gsk3beta inhibitors
(2i) provokes marked transcriptional and epigenetic changes, embodying a shift
toward ground-state pluripotency. In this issue of Cell Stem Cell, Kolodziejczyk
et al. (2015) examine population structures of ESCs while Galonska et al. (2015)
unravel the mechanisms underlying regulatory network rewiring during 2i-mediated
reprogramming.
PMID- 26431179
TI - Two Fresh Streams to Fill the Liver's Hepatocyte Pool.
AB - Differentiated hepatocytes are known for their capacity to regenerate the adult
liver. Two papers discussed here show that distinct subpopulations of adult
hepatocytes may be the crucial populations underpinning such regeneration.
PMID- 26431180
TI - IGFBP3 and T1D: Systemic Factors in Colonic Stem Cell Function and Diabetic
Enteropathy.
AB - Patients with type 1 diabetes (T1D) often experience gastrointestinal enteropathy
(DE) of unclear etiology. Now in Cell Stem Cell, D'Addio et al. (2015) utilize
organoid culture models to study the roles of stem cells in DE and show that
circulating IGF/IGFBP3 controls colonic stem cell function during homeostasis and
in T1D patients.
PMID- 26431181
TI - Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later.
AB - Adult somatic stem cells in various organs maintain homeostatic tissue
regeneration and enhance plasticity. Since its initial discovery five decades
ago, investigations of adult neurogenesis and neural stem cells have led to an
established and expanding field that has significantly influenced many facets of
neuroscience, developmental biology, and regenerative medicine. Here we review
recent progress and focus on questions related to adult mammalian neural stem
cells that also apply to other somatic stem cells. We further discuss emerging
topics that are guiding the field toward better understanding adult neural stem
cells and ultimately applying these principles to improve human health.
PMID- 26431184
TI - Hypertension-related mortality and morbidity.
PMID- 26431182
TI - Single Cell RNA-Sequencing of Pluripotent States Unlocks Modular Transcriptional
Variation.
AB - Embryonic stem cell (ESC) culture conditions are important for maintaining long
term self-renewal, and they influence cellular pluripotency state. Here, we
report single cell RNA-sequencing of mESCs cultured in three different
conditions: serum, 2i, and the alternative ground state a2i. We find that the
cellular transcriptomes of cells grown in these conditions are distinct, with 2i
being the most similar to blastocyst cells and including a subpopulation
resembling the two-cell embryo state. Overall levels of intercellular gene
expression heterogeneity are comparable across the three conditions. However,
this masks variable expression of pluripotency genes in serum cells and
homogeneous expression in 2i and a2i cells. Additionally, genes related to the
cell cycle are more variably expressed in the 2i and a2i conditions. Mining of
our dataset for correlations in gene expression allowed us to identify additional
components of the pluripotency network, including Ptma and Zfp640, illustrating
its value as a resource for future discovery.
PMID- 26431185
TI - Reference values for local arterial stiffness. Part A: carotid artery.
AB - OBJECTIVE: Non-invasive measures of common carotid artery properties, such as
diameter and distension, and pulse pressure, have been widely used to determine
carotid artery distensibility coefficient - a measure of carotid stiffness
(stiffness ~1/distensibility coefficient). Carotid stiffness has been associated
with incident cardiovascular disease (CVD) and may therefore be a useful
intermediate marker for CVD. We aimed to establish age and sex-specific reference
intervals of carotid stiffness. METHODS: We combined data on 22 708 individuals
(age range 15-99 years, 54% men) from 24 research centres worldwide. Individuals
without CVD and established cardiovascular risk factors constituted a healthy sub
population (n = 3601, 48% men) and were used to establish sex-specific equations
for percentiles of carotid distensibility coefficient across age. RESULTS: In the
sub-population without CVD and treatment (n = 12 906, 52% men), carotid
distensibility coefficient Z-scores based on these percentile equations were
independently and negatively associated, in men and women, respectively, with
diabetes {-0.28 [95% confidence interval (CI) -0.41; -0.15] and -0.27 (-0.43;
0.12)}, mean arterial pressure [-0.26 (-0.29; -0.24) and -0.32 (-0.35; -0.29)],
total-to-high-density lipoprotein cholesterol ratio [-0.05 (-0.09; -0.02) and
0.05 (-0.11; 0.01)] and BMI [-0.06 (-0.09; -0.04) and -0.05 (-0.08; -0.02)],
whereas these were positively associated with smoking [0.30 (0.24; 0.36) and 0.24
(0.18; 0.31)]. CONCLUSIONS: We estimated age and sex-specific percentiles of
carotid stiffness in a healthy population and assessed the association between
cardiovascular risk factors and carotid distensibility coefficient Z-scores,
which enables comparison of carotid stiffness values between (patient) groups
with different cardiovascular risk profiles, helping interpretation of such
measures.
PMID- 26431183
TI - Circulating IGF-I and IGFBP3 Levels Control Human Colonic Stem Cell Function and
Are Disrupted in Diabetic Enteropathy.
AB - The role of circulating factors in regulating colonic stem cells (CoSCs) and
colonic epithelial homeostasis is unclear. Individuals with long-standing type 1
diabetes (T1D) frequently have intestinal symptoms, termed diabetic enteropathy
(DE), though its etiology is unknown. Here, we report that T1D patients with DE
exhibit abnormalities in their intestinal mucosa and CoSCs, which fail to
generate in vitro mini-guts. Proteomic profiling of T1D+DE patient serum revealed
altered levels of insulin-like growth factor 1 (IGF-I) and its binding protein 3
(IGFBP3). IGFBP3 prevented in vitro growth of patient-derived organoids via
binding its receptor TMEM219, in an IGF-I-independent manner, and disrupted in
vivo CoSC function in a preclinical DE model. Restoration of normoglycemia in
patients with long-standing T1D via kidney-pancreas transplantation or in
diabetic mice by treatment with an ecto-TMEM219 recombinant protein normalized
circulating IGF-I/IGFBP3 levels and reestablished CoSC homeostasis. These
findings demonstrate that peripheral IGF-I/IGFBP3 controls CoSCs and their
dysfunction in DE.
PMID- 26431186
TI - Reference values for local arterial stiffness. Part B: femoral artery.
AB - OBJECTIVE: Carotid-femoral pulse wave velocity (PWV) is considered the gold
standard measure of arterial stiffness, representing mainly aortic stiffness. As
compared with the elastic carotid and aorta, the more muscular femoral artery may
be differently associated with cardiovascular risk factors (CV-RFs), or, as shown
in a recent study, provide additional predictive information beyond carotid
femoral PWV. Still, clinical application is hampered by the absence of reference
values. Therefore, our aim was to establish age and sex-specific reference values
for femoral stiffness in healthy individuals and to investigate the associations
with CV-RFs. METHODS: Femoral artery distensibility coefficient, the inverse of
stiffness, was calculated as the ratio of relative diastolic-systolic distension
(obtained from ultrasound echo-tracking) and pulse pressure among 5069
individuals (49.5% men, age range: 15-87 years). Individuals without
cardiovascular disease (CVD), CV-RFs and medication use (n = 1489; 43% men)
constituted a healthy subpopulation used to establish sex-specific equations for
percentiles of femoral artery distensibility coefficient across age. RESULTS: In
the total population, femoral artery distensibility coefficient Z-scores were
independently associated with BMI, mean arterial pressure (MAP) and total to high
density lipoprotein (HDL) cholesterol ratio. Standardized betas, in men and
women, respectively, were -0.18 [95% confidence interval (95% CI) -0.23 to -0.13]
and -0.19 (-0.23 to -0.14) for BMI; -0.13 (-0.18 to -0.08) and -0.05 (-0.10 to
0.01) for MAP; and -0.07 (-0.11 to -0.02) and -0.16 (-0.20 to -0.11) for total-to
HDL cholesterol ratio. CONCLUSION: In young and middle-aged men and women, normal
femoral artery stiffness does not change substantially with age up to the sixth
decade. CV-RFs related to metabolic disease are associated with femoral artery
stiffness.
PMID- 26431187
TI - Carotid structure and flow relationship: a potential but unproven prognostic
index.
PMID- 26431188
TI - Blood pressure control in type 2 diabetes over time - what can we learn from
different trajectories?
PMID- 26431189
TI - Blood pressure and early neurological deterioration in acute ischemic stroke.
PMID- 26431190
TI - Blood pressure control after a stroke: a continuing challenge!
PMID- 26431191
TI - Cerebral small vessel disease: role of aortic stiffness and pulsatile
hemodynamics.
PMID- 26431193
TI - Association between serum phosphate and calcium, long-term blood pressure, and
mortality in treated hypertensive adults.
AB - OBJECTIVES: Abnormalities of bone mineral parameters are associated with
cardiovascular morbidity and mortality in patients with chronic kidney disease
and the general population. METHODS: We assessed the impact of baseline serum
phosphate and calcium on longitudinal blood pressure (BP) control and survival in
hypertensive adults. We studied 9260 hypertensive adults followed for 40 years
(151 789 person-years). Changes in BP over initial 5-year follow-up were analysed
using generalized estimating equations. Survival analyses were performed using
Cox proportional hazards model. RESULTS: Serum phosphate levels were higher in
hypertensive women (1.10 mmol/l +/- 0.20) than compared to men (1.02 mmol/l +/-
0.21). In treated hypertensive patients, higher baseline serum phosphate was
significantly associated with poor longitudinal SBP reduction (one standard
deviation increase in phosphate was associated with 0.22 and 0.59 mmHg higher SBP
at 5 years in men and women, respectively). Higher serum phosphate was
significantly associated with all-cause and cardiovascular mortality in men,
whereas in men and women, serum calcium significantly predicted all-cause and
noncardiovascular mortality. In hypertensive patients with chronic kidney
disease, higher phosphate was significantly associated with poorer survival.
CONCLUSION: In hypertensive patients, serum phosphate and calcium are
significantly associated with reduced all-cause and cardiovascular survival and
this appears not to be related to BP control.
PMID- 26431192
TI - Incidence and predictors of hypertension in adults with HIV-initiating
antiretroviral therapy in south-western Uganda.
AB - OBJECTIVE: The successful scale-up of antiretroviral therapy (ART) in sub-Saharan
Africa has led to increasing life expectancy, and thus increased risk of
hypertension. We aimed to describe the incidence and predictors of hypertension
in HIV patients receiving ART at a publicly funded clinic in rural Uganda.
METHODS: We abstracted data from medical records of adult patients who initiated
ART at an HIV clinic in south-western Uganda during 2010-2012. We defined
hypertension as at least two consecutive clinical visits, with a SBP at least 140
mmHg and/or SBP of at least 90 mmHg, or prescription for an antihypertensive
medication. We calculated the incidence of hypertension and fit multivariable Cox
proportional-hazards models to identify predictors of hypertension. RESULTS: A
total of 3389 patients initiated ART without a prior diagnosis of hypertension
during the observation period. Over 3990 person-years of follow-up, 445 patients
developed hypertension, for a crude incidence of 111.5/1000 (95% confidence
interval 101.9-121.7) person-years. Rates were highest among men aged at least 40
years (158.8 per/1000 person-years) and lowest in women aged 30-39 years (80/1000
person-years). Lower CD4 cell count at ART initiation, as well as traditional
risk factors including male sex, increasing age, and obesity, were independently
associated with hypertension. CONCLUSION: We observed a high incidence of
hypertension in HIV-infected persons on ART in rural Uganda, and increased risk
with lower nadir CD4 cell counts. Our findings call for increased attention to
screening of and treatment for hypertension, along with continued prioritization
of early ART initiation.
PMID- 26431194
TI - Increased arterial stiffness is an independent predictor of atrial fibrillation
in hypertensive patients.
AB - OBJECTIVE: Atrial fibrillation is the most common arrhythmia, and confers a high
risk of stroke and heart failure. Hypertension and ageing are two important risk
factors of incident atrial fibrillation and are both associated with increased
arterial stiffness. The possible relationship between arterial stiffness and
atrial fibrillation is insufficiently documented and is probably complex. We
tested these relations in a cohort of hypertensive patients. METHODS: The
population belongs to a registry which includes patients referred before
administration of antihypertensive treatment and fulfilling the following
criteria: office blood pressure (BP) above 140/90 mmHg, essential hypertension,
no history of cardiovascular events, type 1 diabetes or atrial fibrillation, 24-h
ambulatory measurement of BP coupled with the measurement of timing of Korotkoff
sounds to assess arterial stiffness [indexed theoretical value of QKD interval
for a SBP of 100 mmHg, at heart rate (HR) of 60 b.p.m., indexed for height and
QRS duration (QKDh)]. An echocardiographic examination was carried out at
baseline in the majority of patients. Atrial fibrillation-free survival was
analysed with a Cox model including sex, diabetes, smoking,
hypercholesterolaemia, QKDh, average 24-h pulse pressure and mean BP, mean 24-h
HR, BMI and left atrial diameter (LAD), when available. RESULTS: We included 853
patients and recorded 67 new onsets of atrial fibrillation (mean follow-up = 102
+/- 62 months). Analysis found three variables significantly and independently
linked to the occurrence of atrial fibrillation: age, QKDh and 24-h average HR.
When LAD was introduced (n = 480, 35 incident atrial fibrillation), three
variables were linked to incident atrial fibrillation: age, QKDh and LAD.
CONCLUSION: Arterial stiffness is a strong predictor of future atrial
fibrillation in hypertensive patients, independently of age, 24-h pulse pressure
and LAD.
PMID- 26431195
TI - Hypertension screening in children: is it necessary?
PMID- 26431196
TI - Ligand-Based Virtual Screening in a Search for Novel Anti-HIV-1 Chemotypes.
AB - In a search for new anti-HIV-1 chemotypes, we developed a multistep ligand-based
virtual screening (VS) protocol combining machine learning (ML) methods with the
privileged structures (PS) concept. In its learning step, the VS protocol was
based on HIV integrase (IN) inhibitors fetched from the ChEMBL database. The
performances of various ML methods and PS weighting scheme were evaluated and
applied as VS filtering criteria. Finally, a database of 1.5 million commercially
available compounds was virtually screened using a multistep ligand-based
cascade, and 13 selected unique structures were tested by measuring the
inhibition of HIV replication in infected cells. This approach resulted in the
discovery of two novel chemotypes with moderate antiretroviral activity, that,
together with their topological diversity, make them good candidates as lead
structures for future optimization.
PMID- 26431197
TI - Correction: Functional Role of the Disulfide Isomerase ERp57 in Axonal
Regeneration.
PMID- 26431198
TI - Bayesian Population Physiologically-Based Pharmacokinetic (PBPK) Approach for a
Physiologically Realistic Characterization of Interindividual Variability in
Clinically Relevant Populations.
AB - Interindividual variability in anatomical and physiological properties results in
significant differences in drug pharmacokinetics. The consideration of such
pharmacokinetic variability supports optimal drug efficacy and safety for each
single individual, e.g. by identification of individual-specific dosings. One
clear objective in clinical drug development is therefore a thorough
characterization of the physiological sources of interindividual variability. In
this work, we present a Bayesian population physiologically-based pharmacokinetic
(PBPK) approach for the mechanistically and physiologically realistic
identification of interindividual variability. The consideration of a generic and
highly detailed mechanistic PBPK model structure enables the integration of large
amounts of prior physiological knowledge, which is then updated with new
experimental data in a Bayesian framework. A covariate model integrates known
relationships of physiological parameters to age, gender and body height. We
further provide a framework for estimation of the a posteriori parameter
dependency structure at the population level. The approach is demonstrated
considering a cohort of healthy individuals and theophylline as an application
example. The variability and co-variability of physiological parameters are
specified within the population; respectively. Significant correlations are
identified between population parameters and are applied for individual- and
population-specific visual predictive checks of the pharmacokinetic behavior,
which leads to improved results compared to present population approaches. In the
future, the integration of a generic PBPK model into an hierarchical approach
allows for extrapolations to other populations or drugs, while the Bayesian
paradigm allows for an iterative application of the approach and thereby a
continuous updating of physiological knowledge with new data. This will
facilitate decision making e.g. from preclinical to clinical development or
extrapolation of PK behavior from healthy to clinically significant populations.
PMID- 26431199
TI - Understanding Host-Switching by Ecological Fitting.
AB - Despite the fact that parasites are highly specialized with respect to their
hosts, empirical evidence demonstrates that host switching rather than co
speciation is the dominant factor influencing the diversification of host
parasite associations. Ecological fitting in sloppy fitness space has been
proposed as a mechanism allowing ecological specialists to host-switch readily.
That proposal is tested herein using an individual-based model of host switching.
The model considers a parasite species exposed to multiple host resources.
Through time host range expansion can occur readily without the prior evolution
of novel genetic capacities. It also produces non-linear variation in the size of
the fitness space. The capacity for host colonization is strongly influenced by
propagule pressure early in the process and by the size of the fitness space
later. The simulations suggest that co-adaptation may be initiated by the
temporary loss of less fit phenotypes. Further, parasites can persist for
extended periods in sub-optimal hosts, and thus may colonize distantly related
hosts by a "stepping-stone" process.
PMID- 26431200
TI - Phospho-dependent Regulation of SAMHD1 Oligomerisation Couples Catalysis and
Restriction.
AB - SAMHD1 restricts HIV-1 infection of myeloid-lineage and resting CD4+ T-cells.
Most likely this occurs through deoxynucleoside triphosphate triphosphohydrolase
activity that reduces cellular dNTP to a level where reverse transcriptase cannot
function, although alternative mechanisms have been proposed recently. Here, we
present combined structural and virological data demonstrating that in addition
to allosteric activation and triphosphohydrolase activity, restriction correlates
with the capacity of SAMHD1 to form "long-lived" enzymatically competent
tetramers. Tetramer disruption invariably abolishes restriction but has varied
effects on in vitro triphosphohydrolase activity. SAMHD1 phosphorylation also
ablates restriction and tetramer formation but without affecting
triphosphohydrolase steady-state kinetics. However phospho-SAMHD1 is unable to
catalyse dNTP turnover under conditions of nucleotide depletion. Based on our
findings we propose a model for phosphorylation-dependent regulation of SAMHD1
activity where dephosphorylation switches housekeeping SAMHD1 found in cycling
cells to a high-activity stable tetrameric form that depletes and maintains low
levels of dNTPs in differentiated cells.
PMID- 26431202
TI - Non-Steroid Anti-Inflammatory Drugs Are Better than Acetaminophen on Fever
Control at Acute Stage of Fracture.
AB - In addition to adequate surgical fixation and an aggressive rehabilitation
program, pain relief is one of the most critical factors in the acute stage of
fracture treatment. The most common analgesics are nonsteroid anti-inflammatory
drugs and Acetaminophen, both of which relieve pain and reduce body temperature.
In clinical experiences, they exhibit effective pain control; however, their
influence on body temperature remains controversial. This study is aimed at
determining the effects of analgesics at the acute stage of traumatic fracture by
performing a clinical retrospective study of patients with fractures and a
fracture animal model. The retrospective study revealed that, in the
acetaminophen group, the mean value of postmedication body temperature (BT) was
significantly higher than that of the premedication BT. The change in BT was
highly related with the medication rather than other risk factors. Forty eight 12
week-old male Wistar rats were divided into 6 groups: a control group, fracture
group, fracture-Acetaminophen group, Acetaminophen group, fracture-Arcoxia group,
and Arcoxia group. Fracture rats were prepared by breaking their unilateral tibia
and fibula. Their inflammation conditions were evaluated by measuring their serum
cytokine level and their physiological status was evaluated by estimating their
central temperature, heart rate, and mean blood pressure. The hepatic adverse
effects were assessed by measuring the serum levels of aspartate aminotransferase
(sGOT) and alanine aminotransferase (sGPT). The central temperature in the
fracture-Acetaminophen group exceeded that in the groups fed normal saline water
or Arcoxia. Accumulated hepatic injury was presented as steadily ascending curves
of sGOT and sGPT. Inflammation-related cytokine levels were not higher in the
Acetaminophen fracture group and were significantly lower in the fracture-Arcoxia
group. Fever appeared to be aggravated by acetaminophen and more related to the
elevation of hepatic enzymes than to the change in the inflammation-related
cytokines. We suggest that acetaminophen may aggravate fever at the acute stage
of fracture. This response is highly related to the accumulated and exacerbated
side effects of hepatitis that are caused by the medication and trauma.
PMID- 26431203
TI - Re-Classification of Drosophila melanogaster Trichoid and Intermediate Sensilla
Using Fluorescence-Guided Single Sensillum Recording.
AB - Drosophila olfactory receptor neurons are found within specialized sensory hairs
on antenna and maxillary palps. The linking of odorant-induced responses to
olfactory neuron activities is often accomplished via Single Sensillum Recordings
(SSR), in which an electrode inserted into a single sensory hair records the
neuronal activities of all the neurons housed in that sensillum. The
identification of the recorded sensillum requires matching the neuronal responses
with known odor-response profiles. To record from specific sensilla, or to
systematically screen all sensillar types, requires repetitive and semi-random
SSR experiments. Here, we validate an approach in which the GAL4/UAS binary
expression system is used for targeting specific sensilla for recordings. We take
advantage of available OrX-Gal4 lines, in combination with recently generated
strong membrane targeted GFP reporters, to guide electrophysiological recordings
to GFP-labeled sensilla. We validate a full set of reagents that can be used to
rapidly screen the odor-response profiles of all basiconic, intermediate, and
trichoid sensilla. Fluorescence-guided SSR further revealed that two antennal
trichoid sensilla types should be re-classified as intermediate sensilla. This
approach provides a simple and practical addition to a proven method for
investigating olfactory neurons, and can be extended by the addition of UAS-geneX
effectors for gain-of-function or loss-of-function studies.
PMID- 26431201
TI - Exploration of Novel Inhibitors for Class I Histone Deacetylase Isoforms by QSAR
Modeling and Molecular Dynamics Simulation Assays.
AB - Histone deacetylases (HDAC) are metal-dependent enzymes and considered as
important targets for cell functioning. Particularly, higher expression of class
I HDACs is common in the onset of multiple malignancies which results in
deregulation of many target genes involved in cell growth, differentiation and
survival. Although substantial attempts have been made to control the irregular
functioning of HDACs by employing various inhibitors with high sensitivity
towards transformed cells, limited success has been achieved in epigenetic cancer
therapy. Here in this study, we used ligand-based pharmacophore and 2-dimensional
quantitative structure activity relationship (QSAR) modeling approaches for
targeting class I HDAC isoforms. Pharmacophore models were generated by taking
into account the known IC50 values and experimental energy scores with extensive
validations. The QSAR model having an external R2 value of 0.93 was employed for
virtual screening of compound libraries. 10 potential lead compounds (C1-C10)
were short-listed having strong binding affinities for HDACs, out of which 2
compounds (C8 and C9) were able to interact with all members of class I HDACs.
The potential binding modes of HDAC2 and HDAC8 to C8 were explored through
molecular dynamics simulations. Overall, bioactivity and ligand efficiency
(binding energy/non-hydrogen atoms) profiles suggested that proposed hits may be
more effective inhibitors for cancer therapy.
PMID- 26431204
TI - Increased Duration of Heating Boosts Local Drug Deposition during Radiofrequency
Ablation in Combination with Thermally Sensitive Liposomes (ThermoDox) in a
Porcine Model.
AB - INTRODUCTION: Radiofrequency ablation (RFA) is used for the local treatment of
liver cancer. RFA is effective for small (<3 cm) tumors, but for tumors > 3 cm,
there is a tendency to leave viable tumor cells in the margins or clefts of
overlapping ablation zones. This increases the possibility of incomplete ablation
or local recurrence. Lyso-Thermosensitive Liposomal Doxorubicin (LTLD), is a
thermally sensitive liposomal doxorubicin formulation for intravenous
administration, that rapidly releases its drug content when exposed to
temperatures >40 degrees C. When used with RFA, LTLD releases its doxorubicin in
the vasculature around the zone of ablation-induced tumor cell necrosis, killing
micrometastases in the ablation margin. This may reduce recurrence and be more
effective than thermal ablation alone. PURPOSE: The purpose of this study was to
optimize the RFA procedure used in combination with LTLD to maximize the local
deposition of doxorubicin in a swine liver model. Pigs were anaesthetized and the
liver was surgically exposed. Each pig received a single, 50 mg/m2 dose of the
clinical LTLD formulation (ThermoDox(r)). Subsequently, ablations were performed
with either 1, 3 or 6 sequential, overlapping needle insertions in the left
medial lobe with total ablation time of 15, 45 or 90 minutes respectively. Two
different RFA generators and probes were evaluated. After the final ablation, the
ablation zone (plus 3 cm margin) was dissected out and examined for doxorubicin
concentration by LC/MS and fluorescence. CONCLUSION: The mean Cmax of plasma
total doxorubicin was 26.5 MUg/ml at the end of the infusion. Overall, increased
heat time from 15 to 45 to 90 minutes shows an increase in both the amount of
doxorubicin deposited (up to ~100 MUg/g) and the width of the ablation target
margin to which doxorubicin is delivered as determined by tissue homogenization
and LC/MS detection of doxorubicin and by fluorescent imaging of tissues.
PMID- 26431205
TI - Global Metabolomic Profiling of Mice Brains following Experimental Infection with
the Cyst-Forming Toxoplasma gondii.
AB - The interplay between the Apicomplexan parasite Toxoplasma gondii and its host
has been largely studied. However, molecular changes at the metabolic level in
the host central nervous system and pathogenesis-associated metabolites during
brain infection are largely unexplored. We used a global metabolomics strategy to
identify differentially regulated metabolites and affected metabolic pathways in
BALB/c mice during infection with T. gondii Pru strain at 7, 14 and 21 days post
infection (DPI). The non-targeted Liquid Chromatography-Mass Spectrometry (LC-MS)
metabolomics analysis detected approximately 2,755 retention time-exact mass
pairs, of which more than 60 had significantly differential profiles at different
stages of infection. These include amino acids, organic acids, carbohydrates,
fatty acids, and vitamins. The biological significance of these metabolites is
discussed. Principal Component Analysis and Orthogonal Partial Least Square
Discriminant Analysis showed the metabolites' profile to change over time with
the most significant changes occurring at 14 DPI. Correlated metabolic pathway
imbalances were observed in carbohydrate metabolism, lipid metabolism, energetic
metabolism and fatty acid oxidation. Eight metabolites correlated with the
physical recovery from infection-caused illness were identified. These findings
indicate that global metabolomics adopted in this study is a sensitive approach
for detecting metabolic alterations in T. gondii-infected mice and generated a
comparative metabolic profile of brain tissue distinguishing infected from non
infected host.
PMID- 26431206
TI - Assessment of Alveolar Bone Status in Middle Aged Chinese (40-59 Years) with
Chronic Periodontitis--Using CBCT.
AB - OBJECTIVE: This study used con-beam computed tomography (CBCT) to investigate the
prevalence and severity of alveolar bone loss in middle-aged (40-59 years)
Chinese with chronic periodontitis. MATERIALS AND METHODS: The study group
comprised 145 dentate individuals aged 40 to 59 years residing in China who
suffered from chronic periodontitis. CBCT and the application of NNT software
were used to examine the level and location of alveolar bone loss. RESULTS: The
study revealed that 40-59 year old patients with chronic periodontitis had severe
bone loss. At 5,286 sites (34.7%), alveolar bone loss was mild; severe alveolar
bone loss was found at 5,978 sites (39.2%). A comparison of bone loss in
different jaws revealed that the area with the highest degree of bone loss was on
the lingual side of the maxillary molar (56.3 +/- 7.2%), and that the area with
the lowest degree was primarily on the lingual side of the mandibular canine
(27.5 +/- 6.3%). There was a lower degree of alveolar bone loss in males than
females. Differences were observed when comparing the incidence of bone loss
between males and females (P < 0.05). Menopause in females and smoking in both
genders may affect the level of bone loss. Male smokers experienced a greater
degree of bone loss (41.67 +/- 5.76%) than male non-smokers (32.95 +/- 4.31%). A
42.23 +/- 6.34% bone loss was found in menopausal females versus 31.35 +/- 3.62%
in non-menopausal females. CONCLUSIONS: The study revealed that different sites
and teeth exhibited a diverse degree of bone loss. In middle-aged patients with
chronic periodontitis, the highest degrees of bone loss in the incisors,
premolars, and molars were on the lingual side, mesial side and lingual side,
respectively. Menopause in females and smoking may affect the level of bone loss.
PMID- 26431208
TI - Retinal Detachment Due to Retinal Dialysis: Surgical Outcome After Scleral
Buckling.
AB - PURPOSE: The aim of this study was to determine the efficacy and safety of
scleral buckling surgery in retinal detachment due to retinal dialysis. DESIGN:
This study was a prospective, interventional case series. METHODS: A total of 48
eyes of 48 consecutive patients were included after obtaining informed written
consent. Besides taking a thorough history, all eyes were examined by a retinal
surgeon. The macula status, site, and extent of retinal dialysis and
rhegmatogenous retinal detachment (RRD) were particularly noted. Proliferative
vitreoretinopathy grading was done. Buckling was performed by a single surgeon.
At every follow-up, visual acuity, intraocular pressure, retina status, and
buckle position were noted. Any complication found was recorded. Follow-up was
done for at least 6 months. SPSS version 16 was used for data analysis. RESULTS:
We included 48 cases of RRD due to retinal dialysis. The mean +/- SD age of the
patients was 26.85 +/- 15.1 years. The macula was detached in 85.4% of the cases,
and proliferative vitreoretinopathy grade C was found in 25% of the cases. A
surgical reattachment rate of 95.8% was attained after a single primary buckling
procedure. Final Snellen best-corrected visual acuity of 6/18 or better was
attained in 12.5% of the cases. However, 62.5% of the cases had best-corrected
visual acuity in the range of 6/24 to 6/60. Subretinal hemorrhage occurred in
8.3% of cases intraoperatively after subretinal fluid drainage. CONCLUSIONS: We
conclude that scleral buckling has a definite role in the management of RRD due
to retinal dialysis.
PMID- 26431207
TI - CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activity by Promoting
Ubiquitination-Dependent Degradation of the Mammalian CRY1.
AB - The CUL4-DDB1 E3 ligase complex serves as a critical regulator in various
cellular processes, including cell proliferation, DNA damage repair, and cell
cycle progression. However, whether this E3 ligase complex regulates clock
protein turnover and the molecular clock activity in mammalian cells is unknown.
Here we show that CUL4-DDB1-CDT2 E3 ligase ubiquitinates CRY1 and promotes its
degradation both in vitro and in vivo. Depletion of the major components of this
E3 ligase complex, including Ddb1, Cdt2, and Cdt2-cofactor Pcna, leads to CRY1
stabilization in cultured cells or in the mouse liver. CUL4A-DDB1-CDT2 E3 ligase
targets lysine 585 within the C-terminal region of CRY1 protein, shown by the
CRY1 585KA mutant's resistance to ubiquitination and degradation mediated by the
CUL4A-DDB1 complex. Surprisingly, both depletion of Ddb1 and over-expression of
Cry1-585KA mutant enhance the oscillatory amplitude of the Bmal1 promoter
activity without altering its period length, suggesting that CUL4A-DDB1-CDT2 E3
targets CRY1 for degradation and reduces the circadian amplitude. All together,
we uncovered a novel biological role for CUL4A-DDB1-CDT2 E3 ligase that regulates
molecular circadian behaviors via promoting ubiquitination-dependent degradation
of CRY1.
PMID- 26431209
TI - Visual Outcomes of Congenital Cataract Surgery in a Tertiary Public Hospital in
Bangladesh.
AB - PURPOSE: The purpose of this study was to look at the visual outcomes of
bilateral congenital cataract surgery. DESIGN: A prospective study was conducted.
METHODS: A total of 102 eyes of 51 children aged between 2 and 12 months
undergoing bilateral congenital cataract surgery from January 2008 to December
2008 with a 3-year follow-up were included in this study. The study was performed
at a tertiary public hospital. Data were analyzed using SPSS version 17. Chi
square (chi2) tests were performed to identify the association between visual
outcome and age at surgery. P values less than 0.05 were considered statistically
significant. RESULTS: Among the 102 eyes, 32 (31.4%) eyes were operated on when
the subjects were aged between 2 and 3 months, and 70 (68.6%) eyes were operated
on at the age of 3 to 12 months. The subjects were followed up for 3 years after
surgery. Postoperative best-corrected visual acuity was measured. Visual outcomes
were significantly poor in children aged 3 months or older (P < 0.001) as
compared with children aged between 2 and 3 months. CONCLUSIONS: Early detection
and treatment with long-term postoperative rehabilitation is vital to improve
visual outcomes of children with congenital cataract.
PMID- 26431210
TI - Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson
Disease Patients with Probable RBD.
AB - OBJECTIVE: To investigate potential mechanisms involving abnormal iron metabolism
and related inflammation in Parkinson disease (PD) patients with probable rapid
eye movement sleep behavior disorder (PRBD). METHODS: Total 210 PD patients and
31 controls were consecutively recruited. PD patients were evaluated by RBD
Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD
(NPRBD) groups. Demographics information were recorded and clinical symptoms were
evaluated by series of rating scales. Levels of iron and related proteins and
inflammatory factors in cerebrospinal fluid (CSF) and serum were detected.
Comparisons among control, NPRBD and PRBD groups and correlation analyses between
RBDSQ score and levels of above factors were performed. RESULTS: (1) The
frequency of PRBD in PD patients is 31.90%. (2) PRBD group has longer disease
duration, more advanced disease stage, severer motor symptoms and more non-motor
symptoms than NPRBD group. (3) In CSF, levels of iron, transferrin, NO and IL
1beta in PRBD group are prominently increased. RBDSQ score is positively
correlated with the levels of iron, transferrin, NO and IL-1beta in PD group.
Iron level is positively correlated with the levels of NO and IL-1beta in PD
group. (4) In serum, transferrin level is prominently decreased in PRBD group.
PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive
correlation with PGE2 level in PD group. CONCLUSIONS: PRBD is common in PD
patients. PRBD group has severer motor symptoms and more non-motor symptoms.
Excessive iron in brain resulted from abnormal iron metabolism in central and
peripheral systems is correlated with PRBD through neuroinflammation.
PMID- 26431211
TI - P53 Contributes to Cisplatin Induced Renal Oxidative Damage via Regulating P66shc
and MnSOD.
AB - BACKGROUND/AIMS: Cisplatin is widely used to treat malignancies. However, its
major limitation is the development of dose-dependent nephrotoxicity. The precise
mechanisms of cisplatin-induced kidney damage remain unclear. Previous study
demonstrated the central role of mitochondrial ROS (mtROS) in the pathogenesis of
cisplatin nephrotoxicity. The purpose of this study was to explore the mechanism
of mtROS regulation in cisplatin nephrotoxicity. METHODS: p53, MnSOD and p66shc
were detected at mRNA and protein levels by qPCR and western blot in HK2 cells.
mtROS levels were determined by DCFDA and MitoSOX staining. Cell viability and
cell apoptosis were accessed by CCK-8 assay, TUNEL assay and flow cytometry,
respectivesly. siRNAs were used to knock down p53 and p66shc expression and
subsequent changes were observed. In vivo assays using a mouse model of cisplatin
induced acute kidney injury were used to validate the in vitro results. RESULTS:
In HK2 cells, cisplatin exposure decreased the MnSOD and increased the expression
of p53 and p66shc. MnTBAP, a MnSOD mimic, blocked cisplatin-induced the
generation of mtROS and cell injury. P66shc and p53 siRNAs rendered renal cells
resistant to cisplatin-induced mtROS production and cell death. Furthermore,
knockdown of p53 restored MnSOD and inhibiting p66shc. Consistent with these
results, we revealed that p53 inhibitor reduced cisplatin-induced oxidative
stress and apoptosis by regulating MnSOD and p66shc in the kidney of cisplatin
treated mice. CONCLUSION: Our study identifies activation of p53 signalling as a
potential strategy for reducing the nephrotoxicity associated with cisplatin
treatments and, as a result, broadens the therapeutic window of this
chemotherapeutic agent.
PMID- 26431213
TI - Enhancing Asthma Self-Management in Rural School-Aged Children: A Randomized
Controlled Trial.
AB - PURPOSE: To test the effects of 2 modes of delivering an asthma educational
intervention on health outcomes and asthma self-management in school-aged
children who live in rural areas. METHODS: Longitudinal design with data
collected 4 times over 12 months. The target sample was composed of children in
grades 2-5 who had a provider diagnosis of asthma. Elementary schools were
stratified into high or low socioeconomic status based on student enrollment in
the free or reduced-cost lunch program. Schools were then randomly assigned to 1
of 3 treatment arms: in-school asthma class, asthma day camp, or the attention
control group. FINDINGS: Sample retention was good (87.7%) and equally
distributed by study arm. Improvements in emergency department visits and office
visits were related to attending either the asthma class or asthma day camp.
Asthma severity significantly decreased in both asthma treatment groups. Other
factors such as hospitalizations, parent asthma management, and child asthma
management improved for all groups. CONCLUSIONS: Both asthma class and asthma day
camp yielded significant reductions in asthma severity. There were reductions in
the emergency department and office visits for the 2 asthma arms, and
hospitalizations declined significantly for all groups. Asthma self-management
also improved in all groups, while it was somewhat higher in the asthma arms.
This may be due to the attention being drawn to asthma management by study
participation and the action of completing questionnaires about asthma
management, asthma symptoms, and health outcomes.
PMID- 26431212
TI - Molecular switches under TGFbeta signalling during progression from cardiac
hypertrophy to heart failure.
AB - Cardiac hypertrophy is a mechanism to compensate for increased cardiac work load,
that is, after myocardial infarction or upon pressure overload. However, in the
long run cardiac hypertrophy is a prevailing risk factor for the development of
heart failure. During pathological remodelling processes leading to heart
failure, decompensated hypertrophy, death of cardiomyocytes by apoptosis or
necroptosis and fibrosis as well as a progressive dysfunction of cardiomyocytes
are apparent. Interestingly, the induction of hypertrophy, cell death or fibrosis
is mediated by similar signalling pathways. Therefore, tiny changes in the
signalling cascade are able to switch physiological cardiac remodelling to the
development of heart failure. In the present review, we will describe examples of
these molecular switches that change compensated hypertrophy to the development
of heart failure and will focus on the importance of the signalling cascades of
the TGFbeta superfamily in this process. In this context, potential therapeutic
targets for pharmacological interventions that could attenuate the progression of
heart failure will be discussed.
PMID- 26431214
TI - Prophylactic corticosteroids in pulmonary oil embolism after
hysterosalpingography.
PMID- 26431215
TI - Bioimaging of microRNA34c in a single sperm using a molecular beacon.
AB - The VisuFect-conjugated molecular beacon was developed for non-invasive
visualization of microRNA34c in a living single mouse sperm.
PMID- 26431216
TI - The Gateway Hypothesis, Common Liability to Addictions or the Route of
Administration Model A Modelling Process Linking the Three Theories.
AB - BACKGROUND: The aim of this study was to describe the transitions between tobacco
(T), cannabis (C) and other illicit drugs (OIDs) initiations, to simultaneously
explore several substance use theories: gateway theory (GT), common liability
model (CLM) and route of administration model (RAM). METHODS: Data from 2 French
nationwide surveys conducted in 2005 and 2010 were used (16,421 subjects aged 18
34). Using reported ages at initiations, we reconstituted a retrospective cohort
describing all initiation sequences between T, C and OID. Transition
probabilities between the substances were computed using a Markov multi-state
model that also tested the effect of 2 latent variables (item response theory
scores reflecting propensity for early onset and further substance use) on all
transitions. RESULTS: T initiation was associated with increased likelihood of
subsequent C initiation, but the reverse relationship was also observed. While
the most likely initiation sequence among subjects who initiated the 3 groups of
substances was the 'gateway' sequence T x2192; C x2192; OID, this pattern was not
associated with substance use propensity more than alternative sequences. Early
use propensity was associated with the 'gateway' sequence but also with some
alternative ones beginning with T, C or OID. CONCLUSION: If the gateway sequence
appears as the most likely pattern, in line with GT, the effects of early onset
and substance use propensities were also observed for some alternative sequences,
which is more in line with CLM. RAM could explain reciprocal interactions
observed between T and C. This suggests shared influences of individual
(personality traits) and environmental (substance availability, peer influence)
characteristics.
PMID- 26431217
TI - Responses to Intensity-Shifted Auditory Feedback During Running Speech.
AB - PURPOSE: Responses to intensity perturbation during running speech were measured
to understand whether prosodic features are controlled in an independent or
integrated manner. METHOD: Nineteen English-speaking healthy adults (age range =
21-41 years) produced 480 sentences in which emphatic stress was placed on either
the 1st or 2nd word. One participant group received an upward intensity
perturbation during stressed word production, and the other group received a
downward intensity perturbation. Compensations for perturbation were evaluated by
comparing differences in participants' stressed and unstressed peak fundamental
frequency (F0), peak intensity, and word duration during perturbed versus
baseline trials. RESULTS: Significant increases in stressed-unstressed peak
intensities were observed during the ramp and perturbation phases of the
experiment in the downward group only. Compensations for F0 and duration did not
reach significance for either group. CONCLUSIONS: Consistent with previous work,
speakers appear sensitive to auditory perturbations that affect a desired
linguistic goal. In contrast to previous work on F0 perturbation that supported
an integrated-channel model of prosodic control, the current work only found
evidence for intensity-specific compensation. This discrepancy may suggest
different F0 and intensity control mechanisms, threshold-dependent prosodic
modulation, or a combined control scheme.
PMID- 26431219
TI - Progress and Challenges from the Seventh Summit on Breastfeeding.
PMID- 26431218
TI - Chronic Kidney Disease in Non-Diabetic Older Adults: Associated Roles of the
Metabolic Syndrome, Inflammation, and Insulin Resistance.
AB - BACKGROUND: The aims of the study were to examine the association between CKD and
the metabolic syndrome (MetS) and its components in older adults. We also
explored two possible pathways linking the metabolic syndrome with CKD:
inflammation as measured by high sensitivity C-Reactive Protein (hsCRP) and
insulin resistance as measured by HOMA-IR. METHODS: Community-dwelling non
diabetic 70+ adults from the Einstein Aging Study participated in the study. We
defined CKD as eGFR below 60mL/min/1.73m2. MetS was defined according to recent
guidelines from the National Cholesterol Education Program. Binary logistic
regressions were used to assess the association between the metabolic syndrome,
its components and CKD with adjustments for demographics, HOMA-IR and hsCRP.
RESULTS: Of 616 participants (mean age = 79.3 years, 65.5% female), 25% had MetS
and 26.5% had CKD. Participants with CKD had a significantly higher prevalence of
the MetS than individuals without CKD (34.4% vs. 24.3%). Binary logistic
regression models showed that CKD was associated with MetS (OR = 1.72, 95%CI =
1.13-2.61). The association was unaltered by adjustment for hsCRP but altered by
adjustment for HOMA-IR. As the number of MetS components increased the relative
odds of CKD also increased. None of the individual components was independently
associated with CKD. CONCLUSION: MetS is associated with CKD in non-diabetic
older adults. Results showed that as the number of MetS components increased so
did the odds for CKD. HOMA-IR seems to be in the casual pathway linking MetS to
CKD.
PMID- 26431220
TI - The Power of Nutrition and the Power of Breastfeeding.
PMID- 26431221
TI - Breastfeeding Research Supported by the NICHD.
PMID- 26431222
TI - Making the Healthy Choice the Easy Choice.
PMID- 26431231
TI - More Gun Control Ideas.
PMID- 26431225
TI - Endocannabinoid Signaling in the Stress Response of Male and Female Songbirds.
AB - Endocannabinoid (eCB) signaling plays an important role in the stress response
pathways of the mammalian brain, yet its role in the avian stress response has
not been described. Understanding eCB signaling in avian species (such as the
European starling, Sturnus vulgaris) allows a model system that exhibits natural
attenuation of hypothalamic-pituitary-adrenal (HPA) responsiveness to stressors.
Specifically, seasonally breeding birds exhibit the highest HPA activity during
the breeding season and subsequently exhibit a robust HPA down-regulation during
molt. Because eCB signaling in mammals has an overall inhibitory effect on HPA
activity, we expected shifts in eCB signaling to regulate the seasonal HPA down
regulation during molt. However, our data did not support a role for eCB
signaling in the molt-related suppression of HPA activity. For example, injection
of the cannabinoid receptor (CB1) antagonist, AM251, did not potentiate molt
suppressed HPA activity. Instead, our data suggest eCB regulation of HPA
plasticity as birds transition from breeding to molt. In support of this
hypothesis, birds in the late breeding season demonstrated a more dynamic
response at the level of avian amygdala eCB content in response to acute stress.
The response and directionality of this effect match that seen in mammals.
Overall, our data suggest that eCB signaling may allow for a dynamic range in HPA
responsiveness (eg, breeding), but the signaling pathway's role may be limited
when the HPA response is restrained (eg, molt). This first characterization of
eCB signaling in the avian stress response also emphasizes that although the
system functions similarly to other species, its exact role may be species
specific.
PMID- 26431226
TI - Development of an Enhanced Sensitivity Bead-Based Immunoassay for Real-Time In
Vivo Detection of Pancreatic beta-Cell Death.
AB - There is a clinical need for plasma tests to detect and quantify the in vivo
destruction of pancreatic beta-cells in type 1 diabetes. We previously developed
a time-resolved fluorescence immunoassay (TRFIA) to glutamate decarboxylase 65
kDa (GAD65) (GAD65-TRFIA) that was able to detect the synchronous necrotic
destruction of transplanted beta-cells in the hours after their infusion in the
liver. This GAD65-TRFIA, however, lacked sensitivity to detect continued beta
cell rejection beyond this acute phase. The aim of present study was to gain at
least an order of magnitude in analytical sensitivity by switching to Becton
Dickinson cytometric bead array (CBA) (GAD65-CBA) enhanced sensitivity format,
using the same couple of monoclonal antibodies. We compared the performances of
GAD65-CBA and GAD65-TRFIA using Clinical and Laboratory Standards Institute
protocols for linearity, imprecision, specificity, limit of detection, and
functional sensitivity. We conducted a method comparison and assessed the
biologic potential on samples from human recipients of islet grafts. The GAD65
CBA showed acceptable linearity and imprecision. Switching from TRFIA to CBA
lowered functional sensitivity by a factor 35 and lowered limit of detection by a
factor 11 with minimal need for method optimization. The enhanced sensitivity
greatly expands the application domain of our biomarker and allowed for the first
time to detect ongoing beta-cell destruction up to at least 1 day after islet
transplantation. We conclude that the GAD65-CBA is suitable for biological and
clinical assessment of the real-time destruction of beta-cells in intraportal
transplantation.
PMID- 26431232
TI - Postpartum Depression Screening.
PMID- 26431233
TI - A 13-Year-Old Boy with Pancytopenia and a Sacrococcygeal Abscess.
PMID- 26431234
TI - How Much is Too Much? Getting Children Involved, but Not Too Involved.
AB - In the pediatric office, the summer months are filled with well-child visits and
sports physicals. It is during these visits that it is important to evaluate our
patients as a whole, remembering to discuss both physical and emotional concerns.
It is also important to discuss the upcoming school year so concerns by both
parents and children can be addressed. Extracurricular activities play a vital
role in developing social skills, building a sense of community, and allowing
children to discover life-long activities they truly enjoy. However, it is
important to remind parents that as a family they must find a balance between a
busy extracurricular activity schedule and time for rest, relaxation, and family.
PMID- 26431235
TI - Chest Pain in a 17-Year-Old Girl with Chickenpox.
PMID- 26431236
TI - Two Young Children with Rashes on Their Trunk and Extremities.
PMID- 26431238
TI - Adolescent Girls and Abortion.
AB - Abortion is an extremely common procedure in the United States, with
approximately 2% of women having an abortion before age 19 years. Although most
pediatricians do not provide abortions, many will care for a young woman who is
either considering an abortion or has already had one; therefore, the
pediatrician should be able to provide accurate and appropriate counseling about
this option. To provide the best care for adolescent patients considering
abortion, pediatricians must be knowledgeable of aspects of abortion that are
universal to all women and have an understanding of considerations specific to
the adolescent patient. The purpose of this article is to (1) review recent
statistics about teenagers and abortion, (2) explain the different types of
abortion available to teenagers who desire to terminate an unwanted pregnancy,
(3) discuss aspects of abortion unique to the adolescent population, such as
insurance coverage and parental involvement laws, and (4) address common
misconceptions about abortion. [Pediatr Ann. 2015;44(9):384-385,388,390,392.].
PMID- 26431239
TI - What's Normal? Accurately and Efficiently Assessing Menstrual Function.
AB - Many young women are unsure of what constitutes normal menses. By asking focused
questions, pediatric providers can quickly and accurately assess menstrual
function and dispel anxiety and myths. In this article, we review signs and
symptoms of normal versus pathologic menstrual functioning and provide
suggestions to improve menstrual history taking.
PMID- 26431240
TI - Evaluation and Management of Adolescents with Abnormal Uterine Bleeding.
AB - The International Federation of Gynecology and Obstetrics and the American
Congress of Obstetricians and Gynecologists support the use of new terminology
for abnormal uterine bleeding (AUB) to consistently categorize AUB by etiology.
The term AUB can be further classified as AUB/heavy menstrual bleeding (HMB)
(replacing the term "menorrhagia") or AUB/intermenstrual bleeding (replacing the
term "metrorrhagia"). Although many cases of AUB in adolescent women are
attributable to immaturity of the hypothalamic-pituitary-ovarian axis, underlying
bleeding disorders should be considered in women with AUB/HMB. This article
reviews the new terminology for AUB, discusses important relevant features of
history and examination, presents the laboratory evaluation of HMB, and describes
hormonal (oral contraceptive pills, progestin-only methods, long-acting
reversible contraceptives including intrauterine systems), hematologic
(tranexamic acid and desmopressin), and surgical management options for AUB/HMB.
PMID- 26431241
TI - Diagnosis and Management of Polycystic Ovary Syndrome in Adolescent Girls.
AB - Polycystic ovary syndrome (PCOS) is a common endocrine disorder in adolescent
girls that has both reproductive and metabolic implications. Patients with PCOS
typically present to their pediatrician for evaluation of menstrual irregularity
and/or signs of hyperandrogenism, such as hirsutism and acne. The diagnosis of
PCOS is made by clinical symptoms and laboratory evaluation. Because of the long
term health consequences that can accompany the disorder, pediatricians should
consider PCOS in their initial evaluation of menstrual irregularity. Lifestyle
modification is the cornerstone of treatment for girls with PCOS; however,
hormonal medication such as oral contraceptive pills and insulin-sensitizing
agents are useful and effective adjuncts to therapy. The goals of treatment for
girls with PCOS are to improve clinical manifestations of the disorder, health
related quality of life, and long-term health outcomes.
PMID- 26431242
TI - Monthly Periods--Are They Necessary?
AB - Menstrual suppression--the use of hormones to delay or eliminate menses--is often
used in adolescents to manage conditions associated with the menstrual cycle and
to accommodate lifestyle preferences. Reducing the frequency of menstrual
bleeding does not cause any known physiologic harm and has potential short-term
and long-term advantages. Different methods used for menstrual suppression,
however, have associated risks and side effects that need to be weighed against
the benefits of controlling menses. This article reviews the advantages and
disadvantages of menstrual suppression and the different methods available for
adolescents.
PMID- 26431243
TI - Letter to the Editor: Congenital spinal dermal sinus.
PMID- 26431244
TI - Rapid-onset paraparesis and quadriparesis in patients with intramedullary spinal
dermoid cysts: report of 10 cases.
AB - OBJECT Intramedullary dermoid cysts are rare tumors of the spinal cord.
Presentation with rapid onset of paraparesis or quadriparesis (onset within 2
weeks) is rarer still. The authors present their experience in the management and
outcome of patients with such a presentation. METHODS Patient records between
2000 and 2014 were retrospectively reviewed to identify those with intraspinal
dermoid cysts who presented with rapid-onset paraparesis or quadriparesis. Their
clinical, radiological, operative, and follow-up data were analyzed. RESULTS Of a
total of 50 patients with intraspinal dermoid cysts managed during the study
period, 10 (20%) presented with rapid-onset paraparesis or quadriparesis; 9
patients ranged in age from 8 months to 2 years, and 1 patient was 25 years old.
A dermal sinus was seen in the lumbar region of 4 patients, the sacral region of
3, and the thoracic region of 1, and in 1 patient no sinus was found. All except
1 patient presented with rapid-onset paraparesis secondary to infection of the
intramedullary dermoid cyst. One patient presented with rupture of a dermoid cyst
with extension into the central canal up to the medulla. Early surgery was done
soon after presentation in all except 2 patients. Among the 9 patients who
underwent surgery (1 patient did not undergo surgery), total excision of the
intramedullary dermoid cyst was done in 3 patients, near-total excision in 4
patients, and partial excision in 2 patients. Of the 9 patients who underwent
surgery, 8 showed significant improvement in their neurological status, and 1
patient remained stable. The 1 patient who did not undergo surgery died as a
result of an uncontrolled infection after being discharged to a local facility
for management of wound infection. CONCLUSIONS Early recognition of a dermal
sinus and the associated intraspinal dermoid cyst and timely surgical
intervention can eliminate the chances of acute deterioration of neurological
function. Even after an acute onset of paraparesis or quadriparesis, appropriate
antibiotic therapy and prompt surgery can provide reasonably good outcomes in
these patients.
PMID- 26431245
TI - Health-related quality of life in pediatric Chiari Type I malformation: the
Chiari Health Index for Pediatrics.
AB - OBJECT The purpose of this study was to design and validate a patient-reported
health-related quality of life (HRQOL) instrument for pediatric Chiari Type I
malformation (CM-I), the Chiari Health Index for Pediatrics (CHIP). METHODS The
CHIP has 45 items with 4 components making up 2 domain scores, physical (pain
frequency, pain severity, nonpain symptoms) and psychosocial; physical and
psychosocial scores are combined to create an overall HRQOL score. Increasing
scores (0 to 1) represent increasing HRQOL. Fifty-five patients with CM-I (mean
age 12 +/- 4 years, 53% male) were enrolled and completed the CHIP and Health
Utilities Index Mark 3 (HUI3). Twenty-five healthy controls (mean age 11.9 +/- 4
years, 40% male) also completed the CHIP. CHIP scores were compared between these
groups via the Mann-Whitney U-test. For CHIP discriminative function, subscore
versus presence of CM-I was compared via receiver operating characteristic curve
analysis. CHIP scores in the CM-I group were stratified by symptomatology
(asymptomatic, headaches, and paresthesias) and compared via Kruskal-Wallis test
with Mann-Whitney U-test with Bonferroni correction (p < 0.0167). CHIP was
compared with HUI3 (Health Utilities Index Mark 3) via univariate and
multivariate linear regression. RESULTS CHIP physical and psychosocial subscores
were, respectively, 24% and 18% lower in CM-I patients than in controls (p <
0.001); the overall HRQOL score was 23% lower as well (p < 0.001). The area under
the curve (AUC) for CHIP physical subscore versus presence of CM-I was 0.809.
CHIP physical subscore varied significantly with symptomatology (p = 0.001) and
HUI3 pain-related quality of life (R(2) = 0.311, p < 0.001). The AUC for CHIP
psychosocial subscore versus presence of CM-I was 0.754. CHIP psychosocial
subscore varied significantly with HUI3 cognitive- (R(2) = 0.324, p < 0.001) and
emotion-related (R(2) = 0.155, p = 0.003) quality of life. The AUC for CHIP HRQOL
versus presence of CM-I was 0.820. Overall CHIP HRQOL score varied significantly
with symptomatology (p = 0.001) and HUI3 multiattribute composite HRQOL score
(R(2) = 0.440, p < 0.001). CONCLUSIONS The CHIP is a patient-reported, CM-I
specific HRQOL instrument, with construct validity in assessing pain-, cognitive
, and emotion-related quality of life, as well as symptomatic features unique to
CM-I. It holds promise as a discriminative HRQOL index in CM-I outcomes
assessment.
PMID- 26431246
TI - Repair of a traumatic subarachnoid-pleural fistula with the percutaneous
injection of fibrin glue in a 2-year-old.
AB - Subarachnoid-pleural fistulas (SPFs) are rare clinical entities that occur after
severe thoracic trauma or iatrogenic injury during anterolateral approaches to
the spine. Treatment of these fistulas often entails open repair of the dural
defect. The authors present the case of an SPF in a 2-year-old female after a
penetrating injury to the chest. The diagnosis of an SPF was suspected given the
high chest tube output and was confirmed with a positive beta2-transferrin test
of the chest tube fluid, as well as visualization of dural defects on MRI. The
dural defects were successfully repaired with CT-guided percutaneous epidural
injection of fibrin glue alone. This case represents the youngest pediatric
patient with a traumatic SPF to be treated percutaneously. This technique can be
safely used in pediatric patients, offers several advantages over open surgical
repair, and could be considered as an alternative first-line therapy for the
obliteration of SPFs.
PMID- 26431247
TI - Association of postoperative furosemide use with a reduced blood transfusion rate
in sagittal craniosynostosis surgery.
AB - OBJECT A major challenge in sagittal craniosynostosis surgery is the high
transfusion rate (50%-100%) related to blood loss in small pediatric patients.
Several approaches have been proposed to prevent packed red blood cell (PRBC)
transfusion, including endoscopic surgery, erythropoietin ortranexamic acid
administration, and preoperative hemodilution. The authors hypothesized that a
significant proportion of postoperative anemia observed in pediatric patients is
actually dilutional. Consequently, since 2005, at CHU Sainte-Justine, furosemide
has been administered to correct the volemic status and prevent PRBC transfusion.
The purpose of this study was to evaluate the impact of postoperative furosemide
administration on PRBC transfusion rates. METHODS This was a retrospective study
of 96 consecutive patients with sagittal synostosis who underwent surgery at CHU
Sainte-Justine between January 2000 and May 2012. The mean age at surgery was 4.9
+/- 1.5 months (range 2.8-8.7 months). Patients who had surgery before 2005
constituted the control group. Those who had surgery in 2005 or 2006 were
considered part of an implementation phase because furosemide administration was
not routine. Patients who had surgery after 2006 were part of the experimental
(or furosemide) group. Transfusion rates among the 3 groups were compared. The
impact of furosemide administration on transfusion requirement was also measured
while accounting for other variables of interest in a multiple logistic
regression model. RESULTS The total transfusion rate was significantly reduced in
the furosemide group compared with the control group (31.3% vs 62.5%,
respectively; p = 0.009), mirroring the decrease in the postoperative transfusion
rate between the groups (18.3% vs 50.0%, respectively; p = 0.003). The
postoperative transfusion threshold remained similar throughout the study (mean
hemoglobin 56.0 g/dl vs 60.9 g/dl for control and furosemide groups,
respectively; p = 0.085). The proportion of nontransfused patients with recorded
hemoglobin below 70 g/dl did not differ between the control and furosemide groups
(41.7% vs 28.6%, respectively; p = 0.489). Surgical procedure, preoperative
hemoglobin level, estimated blood loss, and furosemide administration
significantly affected the risk of receiving a postoperative PRBC transfusion.
When these variables were analyzed in a multiple logistic regression model,
furosemide administration remained strongly associated with a reduced risk of
being exposed to a blood transfusion (OR 0.196, p = 0.005). There were no
complications related to furosemide administration. CONCLUSIONS A significant
part of the postoperative anemia observed in patients who underwent sagittal
craniosynostosis surgery was due to hypervolemic hemodilution. Correction of the
volemic status with furosemide administration significantly reduces postoperative
PRBC transfusion requirements in these patients.
PMID- 26431248
TI - Atypical pediatric ganglioglioma is common and associated with a less favorable
clinical course.
AB - OBJECT Ganglioglioma (GG) is commonly recognized as a low-grade tumor located in
the temporal lobe, often presenting with seizures. Most are amenable to complete
resection and are associated with excellent oncological outcome. The authors
encountered several GGs in various locations, which seem to have a less favorable
clinical course than GGs in the temporal lobe. METHODS The authors performed a
single-center retrospective review of all children with a histological diagnosis
of GG who were treated at Children's Hospital Colorado between 1997 and 2013.
Each tumor was categorized by 2 pediatric neuroradiologists as typical or
atypical based on preoperative MRI appearance. Typical lesions were cortically
based, within a single cerebral lobe, well-circumscribed, and solid or mixed
solid/cystic. The treatment and clinical course of each patient was analyzed.
RESULTS Thirty-seven children were identified, with a median age at presentation
of 8.2 years and median follow-up of 38.0 months. Eighteen tumors (48.6%) were
typical and 19 (51.4%) were atypical. All typical lesions presented with
seizures, whereas no atypical lesions did so. Sixteen (88.9%) typical lesions
were located in the temporal lobe. In the atypical group, tumor location was
variable, including 11 (57.9%) in the brainstem. Death during follow-up was
statistically more common in the atypical group (31.6% vs 0%, p = 0.02). Gross
total resection (GTR) was achieved for 15 of 16 typical tumors (93.8%), compared
with 3 atypical tumors (15.8%, p < 0.0001). Presentation with seizure or non
brainstem location were each associated with survival (p = 0.02 and 0.004,
respectively). The presence of mutation in BRAF exon 15 did not differ between
the 2 groups. CONCLUSIONS Pediatric GG with typical imaging features is
associated with excellent rates of GTR and overall survival. Atypical GG is
commonly encountered, less amenable to GTR, and associated with a worse outcome.
This may relate to anatomical or biological characteristics and merits further
investigation.
PMID- 26431249
TI - Insulin analogues in pregnancy and specific congenital anomalies: a literature
review.
AB - Insulin analogues are commonly used in pregnant women with diabetes. It is not
known if the use of insulin analogues in pregnancy is associated with any higher
risk of congenital anomalies in the offspring compared with use of human insulin.
We performed a literature search for studies of pregnant women with
pregestational diabetes using insulin analogues in the first trimester and
information on congenital anomalies. The studies were analysed to compare the
congenital anomaly rate among foetuses of mothers using insulin analogues with
foetuses of mothers using human insulin. Of 29 studies, we included 1286 foetuses
of mothers using short-acting insulin analogues with 1089 references of mothers
using human insulin and 768 foetuses of mothers using long-acting insulin
analogues with 685 references of mothers using long-acting human insulin (Neutral
Protamine Hagedorn). The congenital anomaly rate was 4.84% and 4.29% among the
foetuses of mothers using lispro and aspart. For glargine and detemir, the
congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use
of insulin glulisine and degludec in pregnancy were found. There was no
statistically significant difference in the congenital anomaly rate among
foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir)
compared with those exposed to human insulin or Neutral Protamine Hagedorn
insulin. The total prevalence of congenital anomalies was not increased for
foetuses exposed to insulin analogues. The small samples in the included studies
provided insufficient statistical power to identify a moderate increased risk of
specific congenital anomalies.
PMID- 26431250
TI - Drugs with susceptible sites for free radical induced oxidative transformations:
the case of a penicillin.
AB - Penicillins, as bactericidal antibiotics, have been widely used to treat
infections for several decades. Their structure contains both aromatic and
thioether moieties susceptible to free radical oxidation. The (*)OH induced
oxidation mechanism of amoxicillin was investigated by pulse radiolysis
techniques and by final product analysis performed after steady-state gamma
irradiation. The predominant sites of the (*)OH attack are suggested to be the
thioether group, initially yielding an (*)OH adduct to the sulfur, and the
aromatic ring. This adduct to the sulfur converts to sulfur radical cation, which
has three competitive reaction paths: (1) by deprotonation at the adjacent carbon
alpha-(alkylthio)alkyl radicals form, which undergo disproportionation leading
presumably to sulfoxide as main product; (2) via the pseudo-Kolbe mechanism it
may transform to alpha-aminoalkyl radicals; (3) the radical cation can be
stabilized through intramolecular S..O bond formation. The reaction mechanism
suggests the presence of a short-living and a stabilized (via hydrogen bonding)
long-living (*)OH adduct to the sulfur. The three-electron bonded dimers of
amoxicillin were not formed owing to steric hindrance. Thiyl radicals were also
present in equilibrium with alpha-aminoalkyl radicals. In the presence of
dissolved oxygen, aromatic ring hydroxylation occurred along with complex
reactions resulting in e.g. oxidation of the methyl groups. The formation of the
sulfoxide is especially effective in the presence of dissolved oxygen, under
anaerobic condition, however, it is also generated owing to H2O2 and alpha
(alkylthio)alkyl radicals. The thioether moiety appears to be more sensitive to
oxidation compared to the aromatic ring in case of amoxicillin.
PMID- 26431251
TI - Frequency, Type and Cause of Artifacts in Swept-Source and Cirrus HD Optical
Coherence Tomography in Cases of Glaucoma and Suspected Glaucoma.
AB - PURPOSE: To evaluate and compare the frequency, type and cause of imaging
artifacts incurred when using swept-source optical coherence tomography (SS OCT)
and Cirrus HD OCT in the same patients on the same day. MATERIALS AND METHODS:
From left eye OCT results of 72 patients, disc area and macular area data could
be compared between the two types of OCT. For each scan, the final printout
report and source data were examined. For comparison between the two types of
OCT, only source image data were used because of differences in the final
printout report format. RESULTS: There were no significant differences in the
artifact frequencies between the two groups in either area (disc area: 35.9% of
SS OCT, 42.2% of Cirrus OCT, p = 0.523; Macular area: 24.2% of SS OCT, 22.7% of
Cirrus OCT, p = 1.00). The overall results of artifact comparison between the two
types of OCTs also showed no significant differences. Boundary misidentification
was the most common type of artifact observed, and ocular pathology was the most
common cause of artifact in both types of OCTs. Among ocular pathologies, the
epiretinal membrane (ERM) was the most common cause of OCT artifact production in
both types of OCTs. CONCLUSIONS: There was no significant difference in the
frequency, type and cause of artifacts between SS OCT and Cirrus HD OCT.
Artifacts in OCT can influence the interpretation of OCT results. In particular,
ERM around the optic disc could contribute to OCT artifacts and should be
considered in glaucoma diagnosis or during patient follow-up using OCT.
PMID- 26431252
TI - Immunogenicity and safety of early vs delayed BCG vaccination in moderately
preterm (31-33 weeks) infants.
AB - Minimum gestation at which infant can be given BCG (Bacillus Calmette-Guerin)
vaccine safely at birth is not clearly defined. Our objectives were the
following: to compare Mantoux test after 6 months of BCG immunization in
moderately preterm babies (31-33 weeks) vaccinated at birth and 34 weeks post
conception age and to compare in above groups:(a) Interferon - gamma (IFN-gamma)
levels in BCG vaccinated infants who did not react to Mantoux test (b) Local BCG
reaction at 6, 10, 14 weeks and 6 months (c) Complications of BCG vaccination.
Interventional, randomized comparative trial. Moderately preterm infants (31-33
weeks), 90 in each group. At birth, 180 moderately preterm infants were recruited
and randomly allocated into 2 groups. Two ml venous blood was drawn for
estimation of IFN-gamma levels. Infants were given BCG vaccine within 72 hours of
birth and followed up after 2, 4, 6, 10, 14 weeks and 6 months (group 1). Infants
were recruited at birth and held up till 34 weeks post conception age (group 2)
and then given BCG vaccine and followed up similarly as group 1. At each visit,
local BCG reaction, any local or unusual complication and anthropometric
measurements were noted. At six months, Mantoux test was done and 2 ml venous
blood sample was collected for IFN-gamma levels post vaccination. Presence or
absence of BCG local reaction, PPD conversion rates and complications were
analyzed using Chi square or Fisher's exact test. IFN-gamma levels were analyzed
by ANOVA. In all 117 infants could be followed till 6 months after BCG
immunization in 2 groups, and Mantoux test was positive in 38.4% of them. The
rate of Mantoux test positivity was similar irrespective of the age of giving BCG
immunization (group 1- 39.1% vs group 2- 37.5%; p > 0.05). IFN-gamma levels were
significantly raised at 6 months in 60% (n = 21/41) and 65% (n = 15/27) Mantoux
negative infants in group 1 and group 2 respectively. The sequence and order of
local BCG reaction at 2, 4, 6, 10, 14 weeks and 6 months was in the form of
papule, pustule, ulcer, scab and scar. Scar was formed in 94.2% and 89.5% infants
in group 1 and group 2 respectively. One infant in group 1 showed abortive
reaction (0.85%). Only 3.4% of infants developed lymphadenopathy and was similar
in both the groups. Moderately preterm infants (31-33 weeks) exhibited 98.3%
immunogenicity after BCG immunization at birth and can be safely vaccinated
without any risk of severe complications.
PMID- 26431253
TI - Use of Pentamidine As Secondary Prophylaxis to Prevent Visceral Leishmaniasis
Relapse in HIV Infected Patients, the First Twelve Months of a Prospective Cohort
Study.
AB - BACKGROUND: Visceral leishmaniasis (VL) has become an important opportunistic
infection in persons with HIV-infection in VL-endemic areas. The co-infection
leads to profound immunosuppression and high rate of annual VL recurrence. This
study assessed the effectiveness, safety and feasibility of monthly pentamidine
infusions to prevent recurrence of VL in HIV co-infected patients. METHODS: A
single-arm, open-label trial was conducted at two leishmaniasis treatment centers
in northwest Ethiopia. HIV-infected patients with a VL episode were included
after parasitological cure. Monthly infusions of 4 mg/kg pentamidine-isethionate
diluted in normal-saline were started for 12 months. All received antiretroviral
therapy (ART). Time-to-relapse or death was the primary end point. RESULTS:
Seventy-four patients were included. The probability of relapse-free survival at
6 months and at 12 months was 79% and 71% respectively. Renal failure, a possible
drug-related serious adverse event, occurred in two patients with severe
pneumonia. Forty-one patients completed the regimen taking at least 11 of the 12
doses. Main reasons to discontinue were: 15 relapsed, five died and seven became
lost to follow-up. More patients failed among those with a CD4+cell count <= 50
cells/MUl, 5/7 (71.4%) than those with counts above 200 cells/MUl, 2/12 (16.7%),
(p = 0.005). CONCLUSION: Pentamidine secondary prophylaxis led to a 29% failure
rate within one year, much lower than reported in historical controls (50%-100%).
Patients with low CD4+cell counts are at increased risk of relapse despite
effective initial VL treatment, ART and secondary prophylaxis. VL should be
detected and treated early enough in patients with HIV infection before profound
immune deficiency installs.
PMID- 26431255
TI - Incremental Benefit of a Home Visit Following Discharge for Patients with
Multiple Chronic Conditions Receiving Transitional Care.
AB - Transitional care management is effective at reducing hospital readmissions among
patients with multiple chronic conditions, but evidence is lacking on the
relative benefit of the home visit as a component of transitional care. The
sample included non-dual Medicaid recipients with multiple chronic conditions
enrolled in Community Care of North Carolina (CCNC), with a hospital discharge
between July 2010 and December 2012. Using claims data and care management
records, this study retrospectively examined whether home visits reduced the odds
of 30-day readmission compared to less intensive transitional care support, using
multivariate logistic regression to control for demographic and clinical
characteristics. Additionally, the researchers examined group differences within
clinical risk strata on inpatient admissions and total cost of care in the 6
months following hospital discharge. Of 35,174 discharges receiving transitional
care from a CCNC care manager, 21% (N = 7468) included a home visit. In
multivariate analysis, home visits significantly reduced the odds of readmission
within 30 days (odds ratio = 0.52, 95% confidence interval 0.48-0.57). At the 6
month follow-up, home visits were associated with fewer inpatient admissions
within 4 of 6 clinical risk strata, and lower total costs of care for highest
risk patients (average per member per month cost difference $970; P < 0.01). For
complex chronic patients, home visits reduced the likelihood of a 30-day
readmission by almost half compared to less intensive forms of nurse-led
transitional care support. Higher risk patients experienced the greatest benefit
in terms of number of inpatient admissions and total cost of care in the 6 months
following discharge. (Population Health Management 2016;19:163-170).
PMID- 26431254
TI - Metabolic control of the cell cycle.
AB - Cell division is a metabolically demanding process, requiring the production of
large amounts of energy and biomass. Not surprisingly therefore, a cell's
decision to initiate division is co-determined by its metabolic status and the
availability of nutrients. Emerging evidence reveals that metabolism is not only
undergoing substantial changes during the cell cycle, but it is becoming equally
clear that metabolism regulates cell cycle progression. Here, we overview the
emerging role of those metabolic pathways that have been best characterized to
change during or influence cell cycle progression. We then studied how Notch
signaling, a key angiogenic pathway that inhibits endothelial cell (EC)
proliferation, controls EC metabolism (glycolysis) during the cell cycle.
PMID- 26431256
TI - Geriatric Telemedicine.
PMID- 26431258
TI - Using Telehealth to Train Providers of a Cancer Support Intervention.
AB - BACKGROUND: Group interventions are effective for addressing the transition from
cancer treatment to survivorship but are not widely available outside of urban
areas. In addition, minimal training is available for group facilitators outside
of the mental healthcare discipline. Telehealth as a medium can facilitate
conversation and interactive learning and make learning accessible to individuals
in areas that lack resources for traditional classroom teaching. Little is known,
however, regarding the feasibility and acceptability of a telehealth training
program for group leaders. This project aimed to investigate the utility of a
telehealth training program for the delivery of a copyrighted, manualized
psychosocial group intervention, Cancer Transitions: Moving Beyond Treatment.
MATERIALS AND METHODS: Nine group leaders attended one in-person orientation,
four telehealth training classes, and four telehealth supervision sessions,
completing self-report measures of content knowledge, quality satisfaction, and
self-confidence. Following the completion of their last Cancer Transitions
facilitation, group leaders participated in a focus group to provide qualitative
feedback regarding their experiences in training for and leading the respective
groups in eight urban and rural North Carolina communities. RESULTS: Group
leaders rated the training program highly across the domains of content
knowledge, quality satisfaction, and self-confidence. Satisfaction with the
technology itself was equivocal. CONCLUSIONS: Telehealth represents a feasible
avenue for training and supporting leaders of psychosocial interventions. In
addition, telehealth is particularly well suited to the need for training group
leaders in areas outside urban centers or academic communities.
PMID- 26431257
TI - Wearable Sensor/Device (Fitbit One) and SMS Text-Messaging Prompts to Increase
Physical Activity in Overweight and Obese Adults: A Randomized Controlled Trial.
AB - BACKGROUND: Studies have shown self-monitoring can modify health behaviors,
including physical activity (PA). This study tested the utility of a wearable
sensor/device (Fitbit((r)) OneTM; Fitbit Inc., San Francisco, CA) and short
message service (SMS) text-messaging prompts to increase PA in overweight and
obese adults. MATERIALS AND METHODS: Sixty-seven adults wore a Fitbit One tracker
for 6 weeks; half were randomized to also receive three daily SMS-based PA
prompts. The Fitbit One consisted of a wearable tracker for instant feedback on
performance and a Web site/mobile application (app) for detailed summaries.
Outcome measures were objectively measured steps and minutes of PA by intensity
using two accelerometers: ActigraphTM (Pensacola, FL) GT3X+ (primary measure) at
baseline and Week 6 and Fitbit One (secondary measure) at baseline and Weeks 1,
2, 3, 4, 5, and 6. RESULTS: Mixed-model repeated-measures analysis of primary
measures indicated a significant within-group increase of +4.3 (standard error
[SE]=2.0) min/week of moderate- to vigorous-intensity PA (MVPA) at 6-week follow
up (p=0.04) in the comparison group (Fitbit only), but no study group differences
across PA levels. Secondary measures indicated the SMS text-messaging effect
lasted for only 1 week: the intervention group increased by +1,266 steps (SE=491;
p=0.01), +17.8 min/week MVPA (SE=8.5; p=0.04), and +38.3 min/week total PA
(SE=15.9; p=0.02) compared with no changes in the comparison group, and these
between-group differences were significant for steps (p=0.01), fairly/very active
minutes (p<0.01), and total active minutes (p=0.02). CONCLUSIONS: These data
suggest that the Fitbit One achieved a small increase in MVPA at follow-up and
that the SMS-based PA prompts were insufficient in increasing PA beyond 1 week.
Future studies can test this intervention in those requiring less help and/or
test strategies to increase participants' engagement levels.
PMID- 26431259
TI - Expediting Time from Symptoms to Medical Contact Utilizing a Telemedicine Call
Center.
AB - BACKGROUND: No definitive solution has been forthcoming for the often dangerously
long interval between symptom onset and seeking medical care in the prehospital
setting. We examined the implementation of telemedicine technology and
characterization of its utilizers for its efficacy in reducing this possibly life
threatening time lag. MATERIALS AND METHODS: A retrospective observational study
was performed on the working database of an operational telemedicine facility
that included all subscribers. Time-to-contact measurements throughout 2012 were
retrieved from its medical files, and data on age, gender, medical history, and
main complaint were analyzed. RESULTS: Throughout 2012, 22,274 of a total of
46,556 calls (47.8%) were made <=60 min from symptom onset. It is important that
26.9% of all calls (12,522/46,556) were made in <15 min. Significantly more males
(10,794/22,229 [49%]) contacted in <=60 min compared with females (11,480/24,327
[47%], p<0.03). Subjects <60 years of age (2,889/5,717 [51%]) called earlier than
those >60 years (19,386/40,839 [47%], p<0.001). Patients with prior resuscitation
and/or myocardial infarction contacted significantly more rapidly than those with
other cardiac diseases. Over one-half of patients with cardiac complaints
contacted the call center <=60 min from symptom onset, as did those who suffered
physical trauma, but not patients with gastrointestinal symptoms or pain
elsewhere. CONCLUSIONS: A telemedicine system with rapid accessibility to a
professional call center and prompt triage thereafter could be an additional
promising strategy for shortening the interval between symptom onset and call for
medical assistance. Implementation of a widespread telemedicine infrastructure
may bridge the unmet gap between occurrence of symptoms to initiation of medical
treatment.
PMID- 26431260
TI - A Telemedicine Service as Partial Replacement of Face-to-Face Physical
Rehabilitation: The Relevance of Use.
AB - BACKGROUND: Different kinds of telemedicine services have made their entry into
healthcare. In this article we focus on a telerehabilitation service for physical
exercise, designed and implemented as partial replacement of a 3-day outpatient
rehabilitation program for chronic disease patients. The aim of this article is
to examine the use pattern of this telerehabilitation service by chronic disease
patients and to examine the association between actual use and clinical benefit
experienced by these patients. MATERIALS AND METHODS: Chronic lower back pain
(CLBP) patients and pulmonary disease (PD) patients referred to the physical
outpatient rehabilitation programs were asked to participate in and to use the
telerehabilitation service. The actual use was expressed as frequency and
duration of use, and the measurement of clinical benefit focused on complaints
and physical functioning. RESULTS: Sixty-two patients finished the outpatient
rehabilitation using the telerehabilitation service. During the weeks of home
rehabilitation the majority of the patients used the service. On average the
service was used one or two times a week for a total of 35-38 min for both
pathologies, with this value being lower than the time that was replaced.
Frequency of use was significantly associated with the change in physical
functioning outcome for both pathologies (CLBP, r=0.41, p=0.02; PD, r=0.55,
p=0.003). CONCLUSIONS: Chronic disease patients used a telerehabilitation service
as partial replacement of their face-to-face rehabilitation program, and more
frequent use was positively related to higher clinical benefit.
PMID- 26431261
TI - Development and Evaluation of an Evaluation Tool for Healthcare Smartphone
Applications.
AB - INTRODUCTION: Various types of healthcare smartphone applications (apps) have
been released in recent years, making it possible for people to manage their
health anytime and anywhere. As a healthcare provider, who has the responsibility
to provide guidance as to which apps can be used? The purpose of this study was
to develop and evaluate an evaluation tool for the various aspects of healthcare
smartphone apps. MATERIALS AND METHODS: In the first phase, a provisional version
of an evaluation tool for healthcare smartphone apps was developed from a review
of previous studies. In the second phase, the provisional tool was modified and
edited after verification by five experts with regard to its content validity. In
the third phase, from September 25 to October 4, 2013, 200 responses were
collected to verify the construct validity and reliability of the tool. RESULTS:
The edited tool had 23 evaluating items with three evaluating factors along with
seven subevaluating factors as a result of confirmatory factor analysis. The
reliability was found to be high (0.905). CONCLUSIONS: This study is meaningful
because it demonstrates a healthcare smartphone app evaluation tool that is
proven in terms of its validity and reliability. The evaluation tool developed
and tested in this study is an appropriate and widely applicable tool with which
to evaluate healthcare smartphone apps to determine if they are reliable and
useful. However, this evaluation tool represents the beginning of the research in
this area.
PMID- 26431262
TI - Attitudes Toward and Predictors of Videoconferencing Use Among Frequent Family
Visitors to Nursing Home Residents in Taiwan.
AB - BACKGROUND: Videoconferencing with family members benefits nursing home residents
by decreasing their depression and loneliness. Nevertheless, the rate of
participation in videoconferencing by family members is low. The purpose of this
study was to explore attitudes toward and factors related to videoconferencing by
family visitors to nursing home residents in Taiwan. MATERIALS AND METHODS: For
this cross-sectional study, data were collected from 231 family members of
residents at 16 medium to large (>70 beds) nursing homes in Taiwan. Data were
collected on participants' and residents' demographic and clinical
characteristics, acceptance of and attitudes toward using videoconferencing as a
form of nursing home visit, and reasons for/roles during visits to nursing home
residents. Factors related to the use of videoconferencing were analyzed by
logistic regression. RESULTS: Family members' acceptance rate of
videoconferencing use was low (7.8%). The findings also showed that
videoconference use was predicted by hiring a private caregiver (odds
ratio=6.90), the role during/reason for family visits being to maintain
residents' emotional status (odds ratio=5.46), and the frequency of in-person
visits to the nursing home. CONCLUSIONS: We recommend encouraging family use of
videoconferencing by available equipment such as smartphones or tablet programs
that can address residents' emotional issues in a timely fashion. We also suggest
developing more interactive content for videoconferencing, such as a family
oriented picture program to help broaden topics of conversation.
PMID- 26431263
TI - Origin of photogenerated carrier recombination at the metal-active layer
interface in polymer solar cells.
AB - The role of the metal-active layer interface in photogenerated recombination has
been investigated using nanoscale current sensing atomic force microscopy (CS
AFM) and intensity modulated photocurrent spectroscopy (IMPS) in as-deposited,
pre-annealed and post-annealed bulk heterojunction (BHJ) solar cells. Aluminum
(Al) confined post-annealed BHJ solar cells exhibited a significantly improved
device efficiency compared to pre-annealed BHJ solar cells having similar
photocarrier harvesting ability in the active layer. The nanoscale topography and
CS-AFM results indicate a uniform PCBM rich phase at the metal-active layer
interface in the post-annealed cells, but PCBM segregation in the pre-annealed
cells. These two different annealing processes showed different carrier dynamics
revealed using IMPS under various light intensities. The IMPS results suggest
reduced photo generated carrier recombination in uniform PCBM rich post-annealed
BHJ solar cells. This study reveals the importance of the metal-bend interface in
BHJ solar cells in order to obtain efficient charge carrier extraction for high
efficiency.
PMID- 26431264
TI - Cochrane Reviews: Four Proposals for Improvement.
PMID- 26431265
TI - Bioorthogonal Chemoenzymatic Functionalization of Calmodulin for Bioconjugation
Applications.
AB - Calmodulin (CaM) is a widely studied Ca(2+)-binding protein that is highly
conserved across species and involved in many biological processes, including
vesicle release, cell proliferation, and apoptosis. To facilitate biophysical
studies of CaM, researchers have tagged and mutated CaM at various sites,
enabling its conjugation to fluorophores, microarrays, and other reactive
partners. However, previous attempts to add a reactive label to CaM for
downstream studies have generally employed nonselective labeling methods or
resulted in diminished CaM function. Here we report the first engineered CaM
protein that undergoes site-specific and bioorthogonal labeling while retaining
wild-type activity levels. By employing a chemoenzymatic labeling approach, we
achieved selective and quantitative labeling of the engineered CaM protein with
an N-terminal 12-azidododecanoic acid tag; notably, addition of the tag did not
interfere with the ability of CaM to bind Ca(2+) or a partner protein. The
specificity of our chemoenzymatic labeling approach also allowed for selective
conjugation of CaM to reactive partners in bacterial cell lysates, without
intermediate purification of the engineered protein. Additionally, we prepared
CaM-affinity resins that were highly effective in purifying a representative CaM
binding protein, demonstrating that the engineered CaM remains active even after
surface capture. Beyond studies of CaM and CaM-binding proteins, the protein
engineering and surface capture methods described here should be translatable to
other proteins and other bioconjugation applications.
PMID- 26431266
TI - Pre-Operative Antisepsis Protocol Compliance and the Effect on Bacterial Load
Reduction.
AB - BACKGROUND: Adequate skin preparation is essential to preventing surgical site
infection. Many products are available, each with specific manufacturers'
directions. This lack of standardization may lead to incorrect use of the agents
and affect the bacterial load reduction. We hypothesize that a lack of adherence
to utilization protocols for surgical skin antiseptics affects bacterial load
reduction. METHODS: Thirty subjects who routinely perform surgical skin
preparation were recruited from four hospitals. Participants completed a
questionnaire of both demographics and familiarity with two of the most common
skin prep formulas: Chlorhexidine gluconate-isopropyl alcohol (CHG-IPA) and
povidone-iodine (PVI) scrub and paint. Randomly selecting one formula, subjects
performed skin preparation for ankle surgery on a healthy standardized patient.
This was repeated using the second formula on the opposite ankle. Performance was
recorded and reviewed by two independent evaluators using standardized
dichotomous checklists created against the manufacturer's recommended
application. Swabs of the patients' first interweb space and medial malleolus
were obtained before, 1 min after, and 30 min after prep, and plated on Luria
Bertani agar. Bacterial loads were measured in colony forming units (CFUs) for
each anatomical site. Data was analyzed using a univariate linear regression.
RESULTS: Subjects had an average of 12.7 +/- 2.2 y operating room experience and
8.8 +/- 1.5 y of skin prep experience. Despite this, no participant performed
100% of the manufacturers' steps correctly. All essential formula-specific steps
were performed 90% of the time for CHG-IPA and 33.3% for PVI (p = 0.0001). No
correlation was found between experience or familiarity and number of correct
steps for either formula. Average reduction in CFUs was not different between CHG
IPA and PVI at 30 min for all anatomical sites (75.2 +/- 5.4% vs. 73.7 +/- 4.5%,
p = 0.7662). Bacterial reductions at 30 min following skin prep were not
substantially correlated with operator experience, protocol compliance, or total
prep time for either formula. CONCLUSION: This study demonstrates existing
problems with infection prevention as those tasked with pre-operative skin
preparation do so with tremendous incongruence according to manufacturer
guidelines. No effect on bacterial load was identified, however with a larger
sample size this may be noted. Standardization of the prep solutions as well as
simplification and education of the correct techniques may enhance protocol
compliance.
PMID- 26431267
TI - Pressure-Induced Structures and Properties in Indium Hydrides.
AB - The structures, electron properties, and potential superconductivity of indium
hydrides are systematically studied under high pressure by first-principles
density functional calculations. Upon compression, two stable stoichiometries
(InH3 and InH5) are predicted to be thermodynamically stable. Particularly, in
the two compounds, all hydrogen atoms exist in the form of H2 or H3 units. The
stable phases present metallic features with the overlap between the conduction
and the valence bands. The Bader analysis indicates that charges transfer from In
atoms to H atoms. Electron-phonon calculations show that the estimated transition
temperatures (Tc) of InH3 and InH5 are 34.1-40.5 and 22.4-27.1 K at 200 and 150
GPa, respectively.
PMID- 26431268
TI - Role of linezolid therapeutic drug monitoring in the treatment of MRSA tracheo
pulmonary infection in a 10-month-old infant.
AB - The paper reports on the use of therapeutic drug monitoring for linezolid in the
decision-making process to continue or not its administration in an infant.
Linezolid is effective against methicillin-resistant Staphylococcus aureus but is
off-label in pediatrics. The use of therapeutic drug monitoring, as in our case,
allows an informed decision on administration of the drug (in this case on
withdrawal) increasing patients safety.
PMID- 26431269
TI - Diminished Interoceptive Awareness in Fibromyalgia Syndrome.
AB - Sensitivity to signals arising within the body (interoceptive awareness) has been
implicated in emotion processing; interindividual differences in interoceptive
awareness modulate both subjective and physiological indicators of emotional
experience and the regulation of emotion-related behaviors. This study
investigated interoceptive awareness in patients with fibromyalgia syndrome
(FMS), a chronic pain condition accompanied by various affective symptoms.
Interoceptive awareness was assessed in 45 FMS patients and 31 healthy
individuals using a heartbeat perception task. Cognitive performance, comorbid
psychiatric disorders and medication use were assessed as possible confounding
variables. Concerning the primary outcome, patients exhibited markedly reduced
heartbeat perception compared to healthy individuals. Moreover, there was an
inverse relationship between interoceptive awareness and FMS symptom severity.
Reduced interoceptive awareness may be involved in the affective aspects of FMS
pathology. Poor access to bodily signals may restrict patients' ability to
integrate these signals during emotional processing, which, by extension, may
preclude optimal emotional self-regulation.
PMID- 26431270
TI - A response for a cross-sectional case-control study on Parkinson's disease.
PMID- 26431271
TI - A Larger Body Mass Index is Associated with Increased Atherogenic Dyslipidemia,
Insulin Resistance, and Low-Grade Inflammation in Individuals with Metabolic
Syndrome.
AB - BACKGROUND: The consequences of increased body mass index (BMI) on the metabolic
disorders associated with metabolic syndrome (MetS) have not been thoroughly
examined. METHODS: We analyzed data from 262 individuals, 97 men and 165 women
(aged 18-70 years), classified with MetS to investigate whether variations in BMI
could be associated with parameters of dyslipidemia, insulin resistance, or low
grade inflammation. We hypothesized that increases in BMI would positively
correlate with the major dysregulations in metabolism that define MetS. For this
purpose, individuals were separated into four subgroups based on their BMI:
normal weight (<25 kg/m(2)), overweight (>=25 to <30 kg/m(2)), obese (>=30 to <40
kg/m(2)), and morbidly obese (>=40 kg/m(2)). RESULTS: As expected, body weight
and waist circumference increased significantly as BMI increased (P < 0.0001).
Both systolic and diastolic blood pressure were lower in the normal BMI group
compared with the other three BMI groups (P = 0.001). Markers of HDL metabolism
were adversely impacted in elevated BMI groups, as both high-density lipoprotein
cholesterol (HDL-C) and large HDL decreased as BMI increased (P = 0.01). BMI was
negatively correlated with HDL-C (r = -0.193, P = 0.002), HDL size (r = (-)0.227,
P = 0.002), and large HDL (r = -0.147, P = 0.037). In addition, plasma insulin
was highest in subjects classified as morbidly obese (P < 0.0001). There was also
a strong positive correlation between BMI and plasma insulin (r = 0.413, P <
0.0001), whereas adiponectin, a marker of insulin sensitivity, was negatively
correlated with BMI (r = -0.288, P = 0.001). Finally, BMI was positively
correlated with proinflammatory C-reactive protein (r = 0.312, P = 0.0001) and
interleukin-6 (r = 0.238, P = 0.001). CONCLUSIONS: The data from this study
suggest that the physiological factors associated with increased BMI exacerbate
the metabolic abnormalities characteristic of MetS.
PMID- 26431272
TI - Validation of the Greek Cypriot Translation of the Triarchic Psychopathy Measure.
AB - Psychopathy is conceived of as a pathological constellation of personality
traits, manifested in aberrant behavioral, interpersonal, and emotional
tendencies. This study examined within a Greek-speaking nonclinical sample (N =
419) associations between differing phenotypic dimensions of psychopathy
(boldness, meanness, disinhibition) assessed via the Triarchic Psychopathy
Measure (TriPM) and self-report criterion measures of psychopathology,
personality, and history of abuse and neglect. Consistent with predictions of the
triarchic model of psychopathy, evidence was found for distinct correlates of the
3 phenotypic dimensions. Boldness was associated with both adaptive (immunity to
anxiety/distress, fearlessness, low hostility) and maladaptive tendencies
(grandiose manipulative traits, Machiavellian features including desire for
control/status, and verbal aggression). Meanness was related to callous and
unemotional traits, features of Machiavellianism (e.g., amoral manipulation and
distrust of others), physical aggression, and absence of positive parenting.
Disinhibition, by contrast, was characterized by anxiety and distress, exposure
to violence, and retrospective accounts of abuse history, along with impulsive,
irresponsible, and hostile tendencies. These findings indicate that the Greek
Cypriot translation of the TriPM effectively assesses the constructs of the
triarchic model and extend what we know about their empirical correlates.
PMID- 26431274
TI - Endothelial tyrosine kinase receptor B prevents VE-cadherin cleavage and protects
against atherosclerotic lesion development in ApoE-/- mice.
AB - Tyrosine kinase receptor B (TrkB) is a high-affinity receptor for brain-derived
neurotrophic factor (BDNF). In addition to its nervous system functions, TrkB is
also expressed in the aortic endothelium. However, the effects of endothelial
TrkB signaling on atherosclerosis remained unknown. Immunofluorescence analysis
revealed that TrkB expression is downregulated in the endothelium of
atherosclerotic lesions from ApoE-/- mice compared with the atheroma-free aorta
of WT mice. Endothelial TrkB knockdown led to increased lesion size, lipid
deposition and inflammatory responses in the atherosclerotic lesions of the ApoE
/- mice compared with the control mice. Mechanistic studies showed that TrkB
activation prevented VE-cadherin shedding by enhancing the interaction between
vascular endothelial protein tyrosine phosphatase and VE-cadherin, maintaining VE
cadherin in a dephosphorylated state. Our data demonstrate that TrkB is an
endothelial injury-response molecule in atherogenesis. Endothelial BDNF/TrkB
signaling reduces VE-cadherin shedding and protects against atherosclerotic
lesion development in ApoE-/- mice.
PMID- 26431273
TI - Caveolin-1, a stress-related oncotarget, in drug resistance.
AB - Caveolin-1 (Cav-1) is both a tumor suppressor and an oncoprotein. Cav-1
overexpression was frequently confirmed in advanced cancer stages and positively
associated with ABC transporters, cancer stem cell populations, aerobic
glycolysis activity and autophagy. Cav-1 was tied to various stresses including
radiotherapy, fluid shear and oxidative stresses and ultraviolet exposure, and
interacted with stress signals such as AMP-activated protein kinase. Finally, a
Cav-1 fluctuation model during cancer development is provided and Cav-1 is
suggested to be a stress signal and cytoprotective. Loss of Cav-1 may increase
susceptibility to oncogenic events. However, research to explore the underlying
molecular network between Cav-1 and stress signals is warranted.
PMID- 26431275
TI - Antigen spreading-induced CD8+T cells confer protection against the lethal
challenge of wild-type malignant mesothelioma by eliminating myeloid-derived
suppressor cells.
AB - A key focus in cancer immunotherapy is to investigate the mechanism of
efficacious vaccine responses. Using HIV-1 GAG-p24 in a model PD1-based DNA
vaccine, we recently reported that vaccine-elicited CD8+ T cells conferred
complete prevention and therapeutic cure of AB1-GAG malignant mesothelioma in
immunocompetent BALB/c mice. Here, we further investigated the efficacy and
correlation of protection on the model vaccine-mediated antigen spreading against
wild-type AB1 (WT-AB1) mesothelioma. We found that this vaccine was able to
protect mice completely from three consecutive lethal challenges of AB1-GAG
mesothelioma. Through antigen spreading these animals also developed tumor
specific cytotoxic CD8+ T cells, but neither CD4+ T cells nor antibodies,
rejecting WT-AB1 mesothelioma. A majority of these protected mice (90%) were also
completely protected against the lethal WT-AB1 challenge. Adoptive cell transfer
experiments further demonstrated that antigen spreading-induced CD8+ T cells
conferred efficacious therapeutic effects against established WT-AB1 mesothelioma
and prevented the increase of exhausted PD-1+ and Tim-3+ CD8+ T cells. A
significant inverse correlation was found between the frequency of functional PD1
Tim3- CD8+ T cells and that of MDSCs or tumor mass in vivo. Mechanistically, we
found that WT-AB1 mesothelioma induced predominantly polymorphonuclear (PMN)
MDSCs in vivo. In co-cultures with efficacious CD8+ T cells, a significant number
of PMN-MDSCs underwent apoptosis in a dose-dependent way. Our findings indicate
that efficacious CD8+ T cells capable of eliminating both tumor cells and MDSCs
are likely necessary for fighting wild-type malignant mesothelioma.
PMID- 26431278
TI - Dendritic cell metabolism: immunity and tolerance.
PMID- 26431277
TI - PAR1 participates in the ability of multidrug resistance and tumorigenesis by
controlling Hippo-YAP pathway.
AB - The Hippo pathway significantly correlates with organ size control and
tumorigenesis. The activity of YAP/TAZ, a transducer of the Hippo pathway, is
required to sustain self-renewal and tumor-initiation capacities in cancer stem
cells (CSCs). But, upstream signals that control the mammalian Hippo pathway have
not been well understood. Here, we reveal a connection between the Protease
activated receptor 1 (PAR1) signaling pathway and the Hippo-YAP pathway in
gastric cancer stem-like cells. The selective PAR1 agonist TFLLR-NH2 induces an
increase in the fraction of side population cells which is enriched in CSCs, and
promotes tumorigenesis, multi cancer drug resistance, cell morphological change,
and cell invasion which are characteristics of CSCs. In addition, PAR1 activation
inhibits the Hippo-YAP pathway kinase Lats via Rho GTPase. Lats kinase inhibition
in turn results in increased nuclear localization of dephosphorylated YAP.
Furthermore, PAR1 activation confers CSCs related traits via the Hippo-YAP
pathway, and the Hippo-YAP pathway correlates with epithelial mesenchymal
transition which is induced by PAR1 activation. Our research suggests that the
PAR1 signaling deeply participates in the ability of multi drug resistance and
tumorigenesis through interactions with the Hippo-YAP pathway signaling in
gastric cancer stem-like cells. We presume that inhibited YAP is a new
therapeutic target in the treatment human gastric cancer invasion and metastasis
by dysregulated PAR1 or its agonists.
PMID- 26431276
TI - Bortezomib enhances expression of effector molecules in anti-tumor CD8+ T
lymphocytes by promoting Notch-nuclear factor-kappaB crosstalk.
AB - The immunosuppressive tumor microenvironment usurps host antitumor immunity by
multiple mechanisms including interference with the Notch system, which is
important for various metazoan cell fate decisions and hematopoietic cell
differentiation and function. We observed that treatment with the proteasome
inhibitor bortezomib in mice bearing various solid tumors resulted in an
upregulated expression of various Notch signaling components in lymphoid tissues,
thereby increasing CD8+T-lymphocyte IFNgamma secretion and expression of effector
molecules, perforin and granzyme B, as well as the T-box transcription factor
eomesodermin. Bortezomib also neutralized TGFbeta-mediated suppression of
IFNgamma and granzyme B expression in activated CD8+T-cells. Of note, bortezomib
reversed tumor-induced downregulation of Notch receptors, Notch1 and Notch2, as
well as increased the levels of cleaved Notch intracellular domain (NICD) and
downstream targets Hes1 and Hey1 in tumor-draining CD8+T-cells. Moreover,
bortezomib promoted CD8+T-cell nuclear factor-kappaB (NFkappaB) activity by
increasing the total and phosphorylated levels of the IkappaB kinase and
IkappaBalpha as well as the cytoplasmic and nuclear levels of phosphorylated p65.
Even when we blocked NFkappaB activity by Bay-11-7082, or NICD cleavage by gamma
secretase inhibitor, bortezomib significantly increased expression of Notch Hes1
and Hey1 genes as well as perforin, granzyme B and eomesodermin in activated
CD8+T-cells. Data suggest that bortezomib can rescue tumor-induced dysfunction of
CD8+T-cells by its intrinsic stimulatory effects promoting NICD-NFkappaB
crosstalk. These findings provide novel insights on using bortezomib not only as
an agent to sensitize tumors to cell death but also to provide lymphocyte
stimulatory effects, thereby overcoming immunosuppressive actions of tumor on
anti-tumor T-cell functions.
PMID- 26431279
TI - Naa10 in development and disease.
PMID- 26431280
TI - Vinculin-cell membrane interactions.
PMID- 26431291
TI - Approaches to treatment 2: Comparison of American Association of Clinical
Endocrinologists (AACE) and American Diabetes Association (ADA) type 2 diabetes
treatment guidelines.
PMID- 26431292
TI - Letter to the Editor: Screening for Retinopathy of Prematurity in a Tertiary
Ophthalmology Department in Turkey: Incidence, Outcomes, and Risk Factors.
PMID- 26431293
TI - Current Management of Polypoidal Choroidal Vasculopathy.
PMID- 26431294
TI - Optical Coherence Tomography Angiography of Diabetic Retinopathy in Human
Subjects.
AB - BACKGROUND AND OBJECTIVE: Optical coherence tomography angiography (OCTA) is a
novel, non-invasive OCT technique capable of imaging the retinal vasculature.
This study aims to evaluate the retinal microvasculature in diabetic human
subjects with OCTA and assess potential clinical applications. PATIENTS AND
METHODS: Cross-sectional study of 33 subjects with diabetic retinopathy. OCTA was
performed on 3 mm * 3 mm sections using a swept-source OCTA prototype and a phase
and intensity-based contrasting algorithm. OCT angiograms were studied with
corresponding clinical examination and fluorescein angiograms, when available, to
assess accuracy and clinical utility. RESULTS: OCTA was able to demonstrate most
clinically relevant vascular changes in subjects with diabetic retinopathy,
including microaneurysms, impaired vascular perfusion, some forms of intraretinal
fluid, vascular loops, intraretinal microvascular abnormalities,
neovascularization, and cotton-wool spots that were largely consistent with
fluorescein angiography. CONCLUSION: OCTA generates high-resolution angiograms
that illustrate many of the clinically relevant findings in diabetic retinopathy
and offers a novel complement or alternative to fluorescein angiography. Although
currently an investigational technique, OCTA in combination with standard OCT
imaging is at least as good as fluorescein angiography in the evaluation of the
macular complications of diabetic retinopathy.
PMID- 26431295
TI - The Characteristics and Short-term Refractive Error Outcomes of Cystoid Macular
Edema in Premature Neonates as Detected by Spectral-Domain Optical Coherence
Tomography.
AB - BACKGROUND AND OBJECTIVE: To explore characteristics associated with cystoid
macular edema (CME) in neonates screened for retinopathy of prematurity (ROP).
PATIENTS AND METHODS: In this institutional review board-approved, prospective,
observational study, premature neonates underwent imaging with handheld spectral
domain optical coherence tomography. RESULTS: Of 73 included infants (median
gestational age [GA]: 28 weeks, range 23-33 weeks; birth weight: 966 g, range 506
g-1695 g), 28 (38%) had CME and 17/28 (61%) had ROP. CME was associated with ROP
(P=.03) and younger GA (P=.04), but not associated with sex, race, birth weight,
postmenstrual age at imaging, ROP severity, or myopia at median 6 months
corrected age. CME resolved in three cases after bevacizumab treatment for type 1
ROP and in five cases without treatment. CME appeared in two cases several weeks
following injections. CONCLUSION: CME was associated with ROP and younger GA, but
not with myopia. Intravitreal bevacizumab for type 1 ROP has inconclusive effects
on CME.
PMID- 26431296
TI - Choroidal Thickness in Eyes With Central Geographic Atrophy Secondary to
Stargardt Disease and Age-Related Macular Degeneration.
AB - BACKGROUND AND OBJECTIVE: Choroidal thickness (CT) measurements from eyes with
similar areas of macular geographic atrophy (GA) secondary to age-related macular
degeneration (AMD) and Stargardt disease (STGD) were compared to determine
whether GA from different diseases had a similar or different effect on the
underlying subfoveal choroid. PATIENTS AND METHODS: Eyes with the diagnosis of
central GA secondary to STGD and AMD were matched, with subfoveal CT measurements
obtained from the central B-scan using an enhanced depth imaging protocol. The
area of GA was measured using fundus autofluorescence (FAF) imaging. AMD eyes
were divided into those with and without reticular pseudodrusen. RESULTS: A total
of 22 eyes of 22 patients were included in the STGD and AMD groups and were
matched with respect to the area of GA. The mean age of the STGD patients was
48.9 years (standard deviation [SD]=17.1), and the mean age was 81.8 years
(SD=6.2) for the AMD patients. Mean area measurements of GA for the STGD and AMD
groups were 5.4 mm2 (SD=4.1) and 5.1 mm2 (SD=4.0), respectively (P=.83). After
adjusting for age and axial length, eyes with STGD had a mean CT measurement
greater than the AMD eyes (336.1 um vs. 198.1 um, respectively; P=.039). However,
this difference was driven by AMD eyes with reticular pseudodrusen (RPD) and by a
single Stargardt case with a very thick choroid. Eyes with RPD had statistically
thinner subfoveal CT measurements when compared with all other groups.
CONCLUSION: A small but statistically significant increase in the CT of STGD eyes
was observed when compared with normal controls and AMD eyes without RPD.
However, this small increase in CT was driven by a single case with a markedly
thicker choroid within the STGD group, so it is unlikely that a clinically
significant difference exists. However, AMD eyes with GA and RPD had
significantly thinner subfoveal CT measurements.
PMID- 26431297
TI - SLO-Microperimetry in Wet Age-Related Macular Degeneration During Anti-VEGF
Therapy.
AB - BACKGROUND AND OBJECTIVE: To evaluate the morphological and functional outcome of
wet age-related macular degeneration (AMD) during antivascular endothelial growth
factor therapy with bevacizumab using SLO microperimetry (SLO-MP) with eye
tracking. PATIENTS AND METHODS: First, reproducibility was tested over the
choroidal neovascularization (CNV) in 21 eyes of 19 patients with wet AMD.
Second, 21 eyes of 19 patients with active CNV were studied longitudinally during
bevacizumab therapy. Best-corrected visual acuity, SLO-MP, spectral-domain
optical coherence tomography and fluorescein angiography were performed. RESULTS:
There was good reproducibility with a concordance correlation coefficient of
0.85. In the longitudinal study, eyes with anatomical response demonstrated a
significant increase of retinal sensitivity. Non-responders showed no change in
SLO-MP. Retinal sensitivity at baseline had a significant predictive value for
the change in retinal sensitivity during therapy with bevacizumab (P=.032).
CONCLUSION: SLO-MP is able to analyze retinal function overlying lesions in wet
AMD and can be a useful tool to monitor therapy in patients with macular
diseases.
PMID- 26431298
TI - A Central Hyporeflective Subretinal Lucency Correlates With a Region of Focal
Leakage on Fluorescein Angiography in Eyes With Central Serous Chorioretinopathy.
AB - BACKGROUND AND OBJECTIVE: To correlate the appearance of a hyporeflective lucency
on spectral-domain optical coherence tomography (SD-OCT) with a focal leak on
fluorescein angiography (FA) in eyes with central serous chorioretinopathy (CSC).
PATIENTS AND METHODS: Multimodal imaging of 18 patients with CSC who had
hyperreflective fibrin surrounding a hyporeflective lucency on SD-OCT was
analyzed to investigate any potential correlation with an active leak on FA. The
lucent area was evaluated using en face imaging and followed for resolution of
the active leak. RESULTS: High-resolution SD-OCT images of the lucency were found
to correlate with the active leak. In certain cases, the lucent area could be
visualized as communicating with a defect in a pigment epithelial detachment. En
face imaging of the lucency revealed a smoke-stack appearance, and resolution of
the leak correlated with the disappearance of the lucency on SD-OCT. CONCLUSION:
Visualization of a lucency within surrounding fibrin may suggest an active leak.
En face imaging of the lucency may provide insight into the pathophysiology of
the smoke-stack leak on FA.
PMID- 26431299
TI - Randomized Clinical Trial to Compare Micropulse Photocoagulation Versus Half-dose
Verteporfin Photodynamic Therapy in the Treatment of Central Serous
Chorioretinopathy.
AB - BACKGROUND AND OBJECTIVE: To evaluate subthreshold diode-laser micropulse (SDM)
versus half-dose verteporfin photodynamic therapy (hd-PDT) in central serous
chorioretinopathy (CSC). PATIENTS AND METHODS: 62 eyes of 62 patients were
prospectively followed for changes in fluorescein angiography (FA), fundus
autofluorescence (FAF), central macular thickness (CMT), best-corrected visual
acuity (BCVA), and contrast visual acuity (CVA) after SDM (n=20) or hdPDT (n=24).
CSC observation served as control group (n=18). RESULTS: Both treatment groups
(60% SDM vs. 66.7% hdPDT) showed significant improvement in reduction of leakage
activity compared to the control group (37.5%) at 16 weeks. CMT decreased by 69.7
um (SDM), 109.8 um (hdPDT), and 89 um (control). BCVA improved by +6.7 (SDM
group), +8.5 (hdPDT), and +1.5 ETDRS letters (control). CVA was best improved in
the hdPDT group. No secondary RPE alterations could be detected by FAF after any
intervention. CONCLUSION: In comparison to the control group, hdPDT and SDM
resulted in reduced leakage activity in FA and enhanced photopic and scotopic
visual acuity in patients with CSC.
PMID- 26431300
TI - Bevacizumab Versus Ranibizumab in the Treatment of Macular Edema Due to Retinal
Vein Occlusion: 6-Month Results of the CRAVE Study.
AB - BACKGROUND AND OBJECTIVE: To compare efficacy of monthly treatment with
bevacizumab or ranibizumab for macular edema due to retinal vein occlusion.
PATIENTS AND METHODS: Randomized, multicenter, comparative trial
(ClinicalTrials.gov identifier: NCT01428388). Participants were randomized 1:1 to
receive monthly treatment with bevacizumab or ranibizumab. The primary outcome
was change in central foveal thickness at 6 months compared to baseline. RESULTS:
The trial randomized 98 patients to treatment with bevacizumab or ranibizumab. At
6 months, there were no differences in change in central foveal thickness between
groups (bevacizumab: mean reduction of 212.6 um, 95% confidence interval [CI],
288.3 to -137.0; ranibizumab: mean reduction of 243.8 um, 95% CI, -309.6 to
178.0; P=.72, analysis of variance [ANOVA]). Both groups showed similar
functional outcomes (bevacizumab: 0.33 logMAR gain, 95% CI, -0.47 to -0.18;
ranibizumab: 0.34 logMAR gain, 95% CI, -0.45 to -0.23; P=.38, ANOVA). CONCLUSION:
In the treatment of retinal vein occlusion, bevacizumab and ranibizumab have
similar effects on reducing macular thickness and improving visual acuity.
PMID- 26431301
TI - Central Microscotoma: A Rare Presentation of Epiretinal Membranes.
AB - BACKGROUND AND OBJECTIVE: Patients with a symptomatic epiretinal membrane (ERM)
typically complain of metamorphopsia and decreased visual acuity. We describe
three patients who presented with the single complaint of a central microscotoma
due to ERM, an infrequent initial symptom of this entity. PATIENTS AND METHODS:
This is a retrospective, interventional, non-comparative case series. Three
patients with the chief complaint of a central microscotoma related to ERMs who
underwent pars plana vitrectomy by a single surgeon experienced full resolution
of the preoperative microscotoma. Best-corrected visual acuity, fundus
photography, and optical coherence tomography were obtained at each examination.
A comprehensive neuro-ophthalmologic evaluation was performed in all cases,
including magnetic resonance imaging of the orbits and brain, automated visual
fields, multifocal electroretinography, multifocal visually evoked potentials,
and blood tests. RESULTS: Three eyes of three patients who presented with the
initial sole complaint of a central microscotoma due to ERM are included in this
series. A comprehensive neuro-ophthalmologic evaluation ruled out non-retinal
etiologies. After months of observation, a pars plana vitrectomy with ERM and
internal limiting membrane peeling was performed in all patients.
Postoperatively, the patients experienced a complete resolution of their initial,
isolated complaint of a central microscotoma. CONCLUSION: Central microscotoma,
as a rare stand-alone presentation of ERM, is described. This symptom resolved
after a successful removal of the ERM. A greater awareness among clinicians that
ERMs may present in this manner may help avoid excessive and costly medical
evaluations.
PMID- 26431302
TI - Management of Symptomatic Floaters: Current Attitudes, Beliefs, and Practices
Among Vitreoretinal Surgeons.
AB - BACKGROUND AND OBJECTIVE: To assess the current attitudes, beliefs, and practice
patterns among vitreoretinal surgeons when dealing with symptomatic floaters in
patients with otherwise healthy eyes. PATIENTS AND METHODS: A cross-sectional,
Internet-based anonymous survey of 10 questions was distributed via email to
vitreoretinal specialists practicing in the United States. RESULTS: The survey
response rate was 6.1% (159 of 2,600). Forty of 159 respondents (25%) reported
they would perform pars plana vitrectomy (PPV) to reduce symptomatic floaters,
and 110 of 159 (69%) had previously performed PPV for this indication. When
compared to those unlikely to intervene for symptomatic floaters, 33 of 40 (83%)
of those likely to intervene performed more than 100 vitrectomy surgical cases
annually (P<.05). Between those that had and had not performed PPV for
symptomatic floaters in the past, statistically significant differences were
observed regarding the likelihood to perform PPV for symptomatic floaters in the
future (35% vs. 4%; P<.0001) and tendency to elect a procedure if the surgeon's
own vision were impacted by symptomatic floaters (55% vs. 8%; P<.001). When
compared to those likely to perform surgery for symptomatic floaters, those
unlikely to intervene identified three statistically significant barriers: the
surgical risks involved with PPV (28% vs. 86%; P<.001), unrealistic patient
expectations (25% vs 58%; P<.001), and the possibility of ridicule from the local
retina community (10% vs. 32%; P<.01). CONCLUSION: Vitreoretinal specialists are
more likely to intervene for symptomatic floaters if they have previously done so
and if they perform more than 100 surgical cases per year. The major barriers
preventing physicians from performing an intervention for floaters are standard
risks associated with PPV, the fear of unreasonable patient expectations, and the
possibility of ridicule within the local retina community.
PMID- 26431303
TI - Use of the Toric Surgical Marker to Aid in Intraoperative Plaque Placement for
the USC Eye Physics Plaques to Treat Uveal Melanoma: A New Surgical Technique.
AB - BACKGROUND AND OBJECTIVE: To describe a new surgical technique for intraoperative
placement of Eye Physics (EP) plaques for uveal melanoma using a toric marker.
PATIENTS AND METHODS: A toric marker is designed for cataract surgery to align
the axis of astigmatism; its use was modified in this protocol to mark the axis
of suture coordinates as calculated by Plaque Simulator (PS) software. RESULTS:
The toric marker can be used to localize suture coordinates, in degrees, during
intraoperative plaque placement. Linear marking using the toric marker decreases
potential inaccuracies associated with the surgeon estimating 'clock-hours' by
dot placement. CONCLUSION: Use of the toric marker aided surgical placement of EP
plaques. The EP planning protocol is now designed to display the suture
coordinates either by clock-hours or degrees, per surgeon preference. Future
research is necessary to determine whether routine use of the toric marker
improves operative efficiency. [Ophthalmic Surg Lasers Imaging Retina.
2015;46:866-870.].
PMID- 26431304
TI - Image Scaling Difference Between a Confocal Scanning Laser Ophthalmoscope and a
Flash Fundus Camera.
AB - BACKGROUND AND OBJECTIVE: To evaluate scaling and measurement differences between
flash and scanning laser fundus images. PATIENTS AND METHODS: The authors
analyzed fundus autofluorescence images of patients with geographic atrophy
secondary to age-related macular degeneration imaged with both 30o confocal
scanning laser ophthalmoscope (cSLO) and 50o flash fundus camera (FFC). Multiple
vessel-crossing points served as landmarks. RESULTS: The mean (+/-SD; range)
scaling factor between cSLO and FFC images (by GRADOR) for the horizontal
dimension was 1.217 (+/-0.0487; 1.0474-1.272) versus 1.138 (+/-0.0311; 1.0841
1.193) for the vertical dimension. The mean percentage difference between
horizontal and vertical scaling factors was 7.48 (+/-2.29; 2.30-10.70).
Refractive error (focus) and aperture size (or field of view of the image) were
positively correlated and aspect ratio was negatively correlated with landmark
pair measurements. CONCLUSION: Inherent image-scaling differences between fundus
autofluorescence imaging systems are not restricted to simple pixel-to-millimeter
calibration variances, but appear to vary depending on measurement orientation.
Differences should be considered when comparing measurements obtained using
different imaging systems, particularly for clinical trials.
PMID- 26431305
TI - Outer Retinal Changes Preceding Secondary Macular Hole Formation Years After
Vitreomacular Traction Release Demonstrated on Spectral-Domain OCT.
AB - This report describes changes documented on spectral-domain optical coherence
tomography (SD-OCT) in the right eye of a 58-year-old woman who eventually
developed a secondary full-thickness macular hole (FTMH). She had a history of
vitreomacular traction (VMT) that had resolved spontaneously with a complete
posterior vitreous detachment. Despite VMT resolution, a hyperreflective band
from the internal to the external limiting membrane and evidence of photoreceptor
disruption persisted on SD-OCT for 2 years, at which point an FTMH developed.
Despite VMT release, the unexpected FTMH coupled with the preceding outer retinal
changes suggest persistent secondary damage to Muller cells as a potential
factor.
PMID- 26431306
TI - Documentation of Spontaneous Macular Hole Closure in Macular Telangiectasia Type
2 Using Multimodal Imaging.
AB - Macular holes in the setting of macular telangiectasia type 2 can be difficult to
manage. The rates of anatomical closure after macular hole surgery are less
favorable in patients with macular telangiectasia than in those with idiopathic
macular holes. These differences may be due to the influence of unique pathogenic
mechanisms that modulate macular hole dynamics in patients with macular
telangiectasia. In this report, the authors document the multimodal imaging
findings of a patient with macular telangiectasia demonstrating spontaneous
macular hole closure. These findings may improve the understanding of the natural
course of this entity and may have relevance for clinical management.
PMID- 26431307
TI - Flat Electroretinography and Acute Visual Loss After Ocriplasmin Injection for
Vitreomacular Adhesion Complicating Macular Schisis.
AB - A 53-year-old woman with macular and diffuse retinoschisis complicated by
presumed vitreomacular traction underwent unilateral intravitreal ocriplasmin
injection. Within hours after injection, she noted a loss of vision and the
perception of "negative" images in the treated eye. Electrophysiologic testing
revealed flat waveforms, and optical coherence tomography (OCT) showed initial
decreased central macular thickness at day 1, followed by massive increased
macular thickness with subfoveal neurosensory retinal detachment at 1 week. Her
central macular thickness on OCT slowly returned to baseline during a period of 1
month until development of a macula-off rhegmatogenous retinal detachment at 6
months after injection. The authors believe this unique case of vitreomacular
adhesion and macular schisis complicated by post-injection visual loss and
electroretinography changes may offer further insight into this unusual
complication.
PMID- 26431308
TI - Aggressive Surgical Therapy With Early Vitrectomy, Panretinal Photocoagulation,
and Silicone Oil Tamponade for Streptococcus mitis Endophthalmitis.
AB - An 87-year-old woman presented with acute, painful vision loss in her right eye
after intravitreal injection. Examination disclosed hypopyon and vitritis, as
well as discrete inflammatory collections in the vitreous and widespread retinal
hemorrhages. The patient underwent vitrectomy with injection of intravitreal
antibiotics. Vitreous cultures were positive for Streptococcus mitis, a pathogen
associated with severe tissue damage and poor clinical outcomes. Clinical
deterioration prompted repeat vitrectomy with silicone oil tamponade and
panretinal photocoagulation two weeks later, resulting in more favorable anatomic
and visual outcomes. Endophthalmitis caused by exotoxin-producing bacterial
species such as S. mitis is often associated with severe vision loss or loss of
the eye. Aggressive surgical intervention--prompted by concerning clinical
findings and vitreous cultures--may play a role in improving outcomes in these
patients.
PMID- 26431310
TI - High-Strength Single-Walled Carbon Nanotube/Permalloy Nanoparticle/Poly(vinyl
alcohol) Multifunctional Nanocomposite Fiber.
AB - Magnetic nanocomposite fibers are a topic of intense research due to their
potential breakthrough applications such as smart magnetic-field-response devices
and electromagnetic interference (EMI) shielding. However, clustering of
nanoparticles in a polymer matrix is a recognized challenge for obtaining a
property-controllable nanocomposite fiber. Another challenge is that the strength
and ductility of the nanocomposite fiber decrease significantly with increased
weight loading of magnetic nanoparticles in the fiber. Here, we report high
strength single-walled carbon nanotube (SWNT)/permalloy nanoparticle
(PNP)/poly(vinyl alcohol) multifunctional nanocomposite fibers fabricated by wet
spinning. The weight loadings of SWNTs and PNPs in the fiber were as high as 12.0
and 38.0%, respectively. The tensile strength of the fiber was as high as 700
MPa, and electrical conductivity reached 96.7 S m(-1). The saturation
magnetization (Ms) was as high as 24.8 emu g(-1). The EMI attenuation of a fabric
woven from the prepared fiber approached 100% when tested with electromagnetic
waves with a frequency higher than 6 GHz. The present study demonstrates that a
magnetic-field-response device can be designed using the fabricated
multifunctional nanocomposite fiber.
PMID- 26431309
TI - Reconstituting Intracellular Vesicle Fusion Reactions: The Essential Role of
Macromolecular Crowding.
AB - Intracellular vesicle fusion is mediated by SNAREs and Sec1/Munc18 (SM) proteins.
Despite intensive efforts, the SNARE-SM mediated vesicle fusion reaction has not
been faithfully reconstituted in biochemical assays. Here, we present an
unexpected discovery that macromolecular crowding is required for reconstituting
the vesicle fusion reaction in vitro. Macromolecular crowding is known to
profoundly influence the kinetic and thermodynamic behaviors of macromolecules,
but its role in membrane transport processes such as vesicle fusion remains
unexplored. We introduced macromolecular crowding agents into reconstituted
fusion reactions to mimic the crowded cellular environment. In this crowded
assay, SNAREs and SM proteins acted in concert to drive efficient membrane
fusion. In uncrowded assays, by contrast, SM proteins failed to associate with
the SNAREs and the fusion rate decreased more than 30-fold, close to undetectable
levels. The activities of SM proteins were strictly specific to their cognate
SNARE isoforms and sensitive to biologically relevant mutations, further
supporting that the crowded fusion assay accurately recapitulates the vesicle
fusion reaction. Using this crowded fusion assay, we also showed that the SNARE
SM mediated fusion reaction can be modulated by two additional factors: NSF and
alpha-SNAP. These findings suggest that the vesicle fusion machinery likely has
been evolutionarily selected to function optimally in the crowded milieu of the
cell. Accordingly, macromolecular crowding should constitute an integral element
of any reconstituted fusion assay.
PMID- 26431311
TI - Sexual Violence against Men Who Have Sex with Men and Transgender Women in
Mongolia: A Mixed-Methods Study of Scope and Consequences.
AB - The role of sexual violence in health and human rights-related outcomes,
including HIV, is receiving increasing attention globally, yet the prevalence,
patterns, and correlates of sexual violence have been little-studied among men
who have sex with men (MSM) and transgender women in low and middle income
countries. A mixed-methods study with quantitative and qualitative phases was
conducted among MSM and transgender women in Ulaanbaatar, Mongolia. Methods
included respondent-driven sampling (RDS) with structured socio-behavioral
surveys (N = 313) as well as qualitative methods including 30 in-depth interviews
and 2 focus group discussions. Forced sex in the last three years was reported by
14.7% of respondents (RDS-weighted estimate, 95%CI: 9.4-20.1; crude estimate
16.1%, 49/307) in the quantitative phase. A descriptive typology of common
scenarios was constructed based on the specific incidents of sexual violence
shared by respondents in the qualitative phase (37 incidents across 28 interviews
and 2 focus groups). Eight major types of sexual violence were identified, most
frequent of which were bias-motivated street violence and alcohol-involved party
related violence. Many vulnerabilities to and consequences of sexual violence
described during the qualitative phase were also independently associated with
forced sex, including alcohol use at least once per week (AOR = 3.39, 95% CI:1.69
6.81), and having received payment for sex (AOR = 2.77, 95% CI:1.14-6.75).
Building on the promising strategies used in other settings to prevent and
respond to sexual violence, similar strengthening of legal and social sector
responses may provide much needed support to survivors and prevent future sexual
violence.
PMID- 26431312
TI - Advanced Structural Determination of Diterpene Esters Using Molecular Modeling
and NMR Spectroscopy.
AB - Three new jatrophane esters (1-3) were isolated from Euphorbia amygdaloides ssp.
semiperfoliata, including an unprecedented macrocyclic jatrophane ester bearing a
hemiketal substructure, named jatrohemiketal (3). The chemical structures of
compounds 1-3 and their relative configurations were determined by spectroscopic
analysis. The absolute configuration of compound 3 was determined unambiguously
through an original strategy combining NMR spectroscopy and molecular modeling.
Conformational search calculations were performed for the four possible
diastereomers 3a-3d differing in their C-6 and C-9 stereocenters, and the lowest
energy conformer was used as input structure for geometry optimization. The
prediction of NMR parameters ((1)H and (13)C chemical shifts and (1)H-(1)H
coupling constants) by density functional theory (DFT) calculations allowed
identifying the most plausible diastereomer. Finally, the stereostructure of 3
was solved by comparison of the structural features obtained by molecular
modeling for 3a-3d with NMR-derived data (the values of dihedral angles deduced
from the vicinal proton-proton coupling constants ((3)JHH) and interproton
distances determined by ROESY). The methodology described herein provides an
efficient way to solve or confirm structural elucidation of new macrocyclic
diterpene esters, in particular when no crystal structure is available.
PMID- 26431313
TI - Meta-research: Evaluation and Improvement of Research Methods and Practices.
AB - As the scientific enterprise has grown in size and diversity, we need empirical
evidence on the research process to test and apply interventions that make it
more efficient and its results more reliable. Meta-research is an evolving
scientific discipline that aims to evaluate and improve research practices. It
includes thematic areas of methods, reporting, reproducibility, evaluation, and
incentives (how to do, report, verify, correct, and reward science). Much work is
already done in this growing field, but efforts to-date are fragmented. We
provide a map of ongoing efforts and discuss plans for connecting the multiple
meta-research efforts across science worldwide.
PMID- 26431316
TI - Correction: Cysteine String Protein Limits Expression of the Large Conductance,
Calcium-Activated K+ (BK) Channel.
PMID- 26431314
TI - A 24-Hour Study of the Hypothalamo-Pituitary Axes in Huntington's Disease.
AB - BACKGROUND: Huntington's disease is an inherited neurodegenerative disorder
characterised by motor, cognitive and psychiatric disturbances. Patients exhibit
other symptoms including sleep and mood disturbances, muscle atrophy and weight
loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo
pituitary axes. METHODS: We studied neuroendocrine profiles of corticotropic,
somatotropic and gonadotropic hypothalamo-pituitary axes hormones over a 24-hour
period in controlled environment in 15 healthy controls, 14 premanifest and 13
stage II/III Huntington's disease subjects. We also quantified fasting levels of
vasopressin, oestradiol, testosterone, dehydroepiandrosterone sulphate, thyroid
stimulating hormone, free triiodothyronine, free total thyroxine, prolactin,
adrenaline and noradrenaline. Somatotropic axis hormones, growth hormone
releasing hormone, insulin-like growth factor-1 and insulin-like factor binding
protein-3 were quantified at 06:00 (fasting), 15:00 and 23:00. A battery of
clinical tests, including neurological rating and function scales were performed.
RESULTS: 24-hour concentrations of adrenocorticotropic hormone, cortisol,
luteinizing hormone and follicle-stimulating hormone did not differ significantly
between the Huntington's disease group and controls. Daytime growth hormone
secretion was similar in control and Huntington's disease subjects. Stage II/III
Huntington's disease subjects had lower concentration of post-sleep growth
hormone pulse and higher insulin-like growth factor-1:growth hormone ratio which
did not reach significance. In Huntington's disease subjects, baseline levels of
hypothalamo-pituitary axis hormones measured did not significantly differ from
those of healthy controls. CONCLUSIONS: The relatively small subject group means
that the study may not detect subtle perturbations in hormone concentrations. A
targeted study of the somatotropic axis in larger cohorts may be warranted.
However, the lack of significant results despite many variables being tested does
imply that the majority of them do not differ substantially between HD and
controls.
PMID- 26431315
TI - Comparative Analysis of Cell-Associated HIV DNA Levels in Cerebrospinal Fluid and
Peripheral Blood by Droplet Digital PCR.
AB - BACKGROUND: Measurement of HIV DNA-bearing cells in cerebrospinal fluid (CSF) is
challenging because few cells are present. We present a novel application of the
sensitive droplet digital (dd)PCR in this context. METHODS: We analyzed CSF cell
pellets and paired peripheral blood mononuclear cells (PBMC) from 28 subjects, 19
of whom had undetectable HIV RNA (<48 copies/mL) in both compartments. We
extracted DNA from PBMC using silica-based columns and used direct lysis on CSF
cells. HIV DNA and the host housekeeping gene (RPP30) were measured in CSF and
PBMC by (dd)PCR. We compared HIV DNA levels in virally-suppressed and
unsuppressed subgroups and calculated correlations between HIV DNA and RNA levels
in both compartments using non-parametric tests. RESULTS: HIV DNA was detected in
18/28 (64%) CSF cell pellets, including 10/19 (53%) samples with undetectable HIV
RNA. HIV DNA levels in CSF cell pellets were not correlated with RPP30 (p = 0.3),
but correlated positively with HIV RNA in CSF (p = 0.04) and HIV DNA in PBMC (p =
0.03). Cellular HIV DNA in CSF was detected in comparable levels in HIV RNA
suppressed and unsuppressed subjects (p = 0.14). In contrast, HIV DNA levels in
PBMC were significantly lower in HIV RNA-suppressed than in unsuppressed subjects
(p = 0.014). Among subjects with detectable HIV DNA in both compartments, HIV DNA
levels in CSF were significantly higher than in PBMC (p<0.001). CONCLUSIONS:
Despite low mononuclear cell numbers in CSF, HIV DNA was detected in most virally
suppressed individuals. In contrast to PBMC, suppressive ART was not associated
with lower HIV DNA levels in CSF cells, compared to no ART, perhaps due to poorer
ART penetration, slower decay of HIV DNA, or enrichment of HIV DNA-bearing
mononuclear cells into the CSF, compared to blood. Future studies should
determine what fraction of HIV DNA is replication-competent in CSF leukocytes,
compared to PBMC.
PMID- 26431317
TI - Synergistic Gene Expression Signature Observed in TK6 Cells upon Co-Exposure to
UVC-Irradiation and Protein Kinase C-Activating Tumor Promoters.
AB - Activation of stress response pathways in the tumor microenvironment can promote
the development of cancer. However, little is known about the synergistic tumor
promoting effects of stress response pathways simultaneously induced in the tumor
microenvironment. Therefore, the purpose of this study was to establish gene
expression signatures representing the interaction of pathways deregulated by
tumor promoting agents and pathways induced by DNA damage. Human lymphoblastoid
TK6 cells were pretreated with the protein kinase C activating tumor promoter 12
O-tetradecanoylphorbol-13-acetate (TPA) and exposed to UVC-irradiation. The time
and dose-responsive effects of the co-treatment were captured with RNA-sequencing
(RNA-seq) in two separate experiments. TK6 cells exposed to both TPA and UVC had
significantly more genes differentially regulated than the theoretical sum of
genes induced by either stress alone, thus indicating a synergistic effect on
global gene expression patterns. Further analysis revealed that TPA+UVC co
exposure caused synergistic perturbation of specific genes associated with p53,
AP-1 and inflammatory pathways important in carcinogenesis. The 17 gene signature
derived from this model was confirmed with other PKC-activating tumor promoters
including phorbol-12,13-dibutyrate, sapintoxin D, mezerein, (-)-Indolactam V and
resiniferonol 9,13,14-ortho-phenylacetate (ROPA) with quantitative real-time PCR
(QPCR). Here we show a novel gene signature that may represent a synergistic
interaction in the tumor microenvironment that is relevant to the mechanisms of
chemical induced tumor promotion.
PMID- 26431318
TI - Effectiveness of probiotics in type 2 diabetes: a meta-analysis.
AB - INTRODUCTION: An increasing number of studies suggest that the use of probiotics
may have a beneficial effect in patients with type 2 diabetes. OBJECTIVES: The
aim of the study was to assess the ability of probiotics to modify selected
cardiometabolic risk factors in subjects with type 2 diabetes. METHODS: PubMed,
Embase, Cochrane Library, and Scopus databases were thoroughly reviewed up to
January 2015 to search for randomized controlled trials (RCTs) that examined the
effect of probiotics on selected modifiable cardiometabolic parameters in
patients with type 2 diabetes. The following endpoints were considered: fasting
plasma glucose (FPG), insulin concentration, insulin resistance, hemoglobin A1c
(HbA1c), as well as the levels of total cholesterol, triglycerides, low-density
and high-density lipoprotein cholesterols, and C-reactive protein (CRP). A total
of 571 RCTs were initially identified, of which 8 trials with 438 individuals
were selected for meta-analysis. The effects of probiotics were calculated for
each parameter. RESULTS: The meta-analysis showed a significant effect of
probiotics on reducing HbA1c levels (standardized mean difference [SMD], -0.81;
confidence interval [CI], -1.33 to -0.29, P = 0.0023; I2 = 68.44%; P = 0.0421 for
heterogeneity) and HOMA-IR (SMD, -2.10; CI -3.00 to -1.20, P <0.001; I2 = 82.91%;
P = 0.0029 for heterogeneity). Supplementation with probiotics did not have a
significant effect on FPG, insulin, and CRP levels as well as the lipid profile.
CONCLUSIONS: Our meta-analysis suggests that probiotic supplementation might
improve, at least to some extent, metabolic control in subjects with type 2
diabetes. However, larger well-designed, longterm RCTs are needed to confirm any
potentially beneficial relationship between the use of probiotics and modifiable
cardiometabolic risk factors in patients with type 2 diabetes.
PMID- 26431319
TI - In Vitro Coinfection and Replication of Classical Swine Fever Virus and Porcine
Circovirus Type 2 in PK15 Cells.
AB - Increasing clinical lines of evidence have shown the coinfection/superinfection
of porcine circovirus type 2 (PCV2) and classical swine fever virus (CSFV). Here,
we investigated whether PCV2 and CSFV could infect the same cell productively by
constructing an in vitro coinfection model. Our results indicated that PCV2-free
PK15 cells but not ST cells were more sensitive to PCV2, and the PK15 cell line
could stably harbor replicating CSFV (PK15-CSFV cells) with a high infection
rate. Confocal and super-resolution microscopic analysis showed that PCV2 and
CSFV colocalized in the same PK15-CSFV cell, and the CSFV E2 protein translocated
from the cytoplasm to the nucleus in PK15-CSFV cells infected with PCV2.
Moreover, PCV2-CSFV dual-positive cells increased gradually in PK15-CSFV cells in
a PCV2 dose-dependent manner. In PK15-CSFV cells, PCV2 replicated well, and the
production of PCV2 progeny was not influenced by CSFV infection. However, CSFV
reproduction decreased in a PCV2 dose-dependent manner. In addition, cellular
apoptosis was not strengthened in PK15-CSFV cells infected with PCV2 in
comparison with PCV2-infected PK15 cells. Moreover, using this coinfection model
we further demonstrated PCV2-induced apoptosis might contribute to the impairment
of CSFV HCLV strain replication in coinfected cells. Taken together, our results
demonstrate for the first time the coinfection/superinfection of PCV2 and CSFV
within the same cell, providing an in vitro model to facilitate further
investigation of the underlying mechanism of CSFV and PCV2 coinfection.
PMID- 26431320
TI - Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian
Function in Chemotherapy-Injured Ovaries.
AB - Early menopause and infertility often occur in female cancer patients after
chemotherapy (CTx). For these patients, oocyte/embryo cryopreservation or ovarian
tissue cryopreservation is the current modality for fertility preservation.
However, the above methods are limited in the long-term protection of ovarian
function, especially for fertility preservation (very few females with cancer
have achieved pregnancy with cryopreserved ovarian tissue or eggs until now). In
addition, the above methods are subject to their scope (females with no husband
or prepubertal females with no mature oocytes). Thus, many females who suffer
from cancers would not adopt the above methods pre- and post-CTx due to their
uncertainty, safety and cost-effectiveness. Therefore, millions of women have
achieved long-term survival after thorough CTx treatment and have desired to
rescue their ovarian function and fertility with economic, durable and reliable
methods. Recently, some studies showed that mice with infertility caused by CTx
can produce normal offspring through intraovarian injection of exogenous female
germline stem cells (FGSCs). Though exogenous FGSC can be derived from mice
without immune rejection in the same strain, it is difficult to obtain human
female germline stem cells (hFGSCs), and immune rejection could occur between
different individuals. In this study, infertility in mice was caused by CTx, and
the ability of FGSCs to restore ovarian function or even produce offspring was
assessed. We had successfully isolated and purified the FGSCs from adult female
mice two weeks after CTx. After infection with GFP-carrying virus, the FGSCs were
transplanted into ovaries of mice with infertility caused by CTx. Finally,
ovarian function was restored and the recipients produced offspring long-term.
These findings showed that mice with CTx possessed FGSCs, restoring ovarian
function and avoiding immune rejection from exogenous germline stem cells.
PMID- 26431322
TI - Novel Management Options for Adult Patients With Progressive Acute Lymphoblastic
Leukemia: A Case-Study Compendium.
AB - Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy
characterized by highly proliferative immature lymphoid cells in the bone marrow
and peripheral blood. In adults, ALL accounts for approximately 20% of all adult
leukemias. ALL carries a poor prognosis in adults. The 5-year overall survival is
24% in patients ages 40 to 59 years and 18% in patients ages 60 to 69 years. ALL
can be grouped into different categories according to its cell lineage (B cell or
T cell), the presence or absence of the Philadelphia chromosome, and various
cytogenetic and molecular classifications. A main goal of treatment is to allow
the patient to achieve a complete remission and to consolidate this remission
with either a maintenance regimen or an allogeneic stem cell transplant. Although
the overall rate of complete remission following frontline therapy for newly
diagnosed ALL is high, the majority of patients experience a disease relapse. In
general, the duration of initial complete remission impacts the patient's
prognosis and response to further therapies. Subsequent treatments must balance
the goal of achieving a remission with the need for the patient to maintain or
improve quality of life. Recently approved agents, such as blinatumomab and
vincristine sulfate liposome injection, offer the promise of a second remission
that can serve as a bridge to allogeneic stem cell transplant while still
maintaining quality of life. A novel approach using adoptive cellular
immunotherapy with chimeric antigen receptor (CAR) T cells is associated with
extremely robust responses.
PMID- 26431321
TI - Genetically and Phenotypically Distinct Pseudomonas aeruginosa Cystic Fibrosis
Isolates Share a Core Proteomic Signature.
AB - The opportunistic pathogen Pseudomonas aeruginosa is among the main colonizers of
the lungs of cystic fibrosis (CF) patients. We have isolated and sequenced
several P. aeruginosa isolates from the sputum of CF patients and compared them
with each other and with the model strain PAO1. Phenotypic analysis of CF
isolates showed significant variability in colonization and virulence-related
traits suggesting different strategies for adaptation to the CF lung. Genomic
analysis indicated these strains shared a large set of core genes with the
standard laboratory strain PAO1, and identified the genetic basis for some of the
observed phenotypic differences. Proteomics revealed that in a conventional
laboratory medium PAO1 expressed 827 proteins that were absent in the CF isolates
while the CF isolates shared a distinctive signature set of 703 proteins not
detected in PAO1. PAO1 expressed many transporters for the uptake of organic
nutrients and relatively few biosynthetic pathways. Conversely, the CF isolates
expressed a narrower range of transporters and a broader set of metabolic
pathways for the biosynthesis of amino acids, carbohydrates, nucleotides and
polyamines. The proteomic data suggests that in a common laboratory medium PAO1
may transport a diverse set of "ready-made" nutrients from the rich medium,
whereas the CF isolates may only utilize a limited number of nutrients from the
medium relying mainly on their own metabolism for synthesis of essential
nutrients. These variations indicate significant differences between the
metabolism and physiology of P. aeruginosa CF isolates and PAO1 that cannot be
detected at the genome level alone. The widening gap between the increasing
genomic data and the lack of phenotypic data means that researchers are
increasingly reliant on extrapolating from genomic comparisons using
experimentally characterized model organisms such as PAO1. While comparative
genomics can provide valuable information, our data suggests that such
extrapolations may be fraught with peril.
PMID- 26431326
TI - Rapamycin preserves gut homeostasis during Drosophila aging.
AB - Gut homeostasis plays an important role in maintaining the overall body health
during aging. Rapamycin, a specific inhibitor of mTOR, exerts prolongevity
effects in evolutionarily diverse species. However, its impact on the intestinal
homeostasis remains poorly understood. Here, we demonstrate that rapamycin can
slow down the proliferation rate of intestinal stem cells (ISCs) in the aging
guts and induce autophagy in the intestinal epithelium in Drosophila. Rapamycin
can also significantly affect the FOXO associated genes in intestine and up
regulate the negative regulators of IMD/Rel pathway, consequently delaying the
microbial expansion in the aging guts. Collectively, these findings reveal that
rapamycin can delay the intestinal aging by inhibiting mTOR and thus keeping stem
cell proliferation in check. These results will further explain the mechanism of
healthspan and lifespan extension by rapamycin in Drosophila.
PMID- 26431327
TI - Identification of ageing-associated naturally occurring peptides in human urine.
AB - To assess normal and pathological peptidomic changes that may lead to an improved
understanding of molecular mechanisms underlying ageing, urinarypeptidomes of
1227 healthy and 10333 diseased individuals between 20 and 86 years of age were
investigated. The diseases thereby comprised diabetes mellitus, renal and
cardiovascular diseases. Using age as a continuous variable, 116 peptides were
identified that significantly (p < 0.05; |rho|>=0.2) correlated with age in the
healthy cohort. The same approach was applied to the diseased cohort. Upon
comparison of the peptide patterns of the two cohorts 112 common age-correlated
peptides were identified. These 112 peptides predominantly originated from
collagen, uromodulin and fibrinogen. While most fibrillar and basement membrane
collagen fragments showed a decreased age-related excretion, uromodulin, beta-2
microglobulin and fibrinogen fragments showed an increase. Peptide-based in
silico protease analysis was performed and 32 proteases, including matrix
metalloproteinases and cathepsins, were predicted to be involved in ageing.
Identified peptides, predicted proteases and patient information were combined in
a systems biology pathway analysis to identify molecular pathways associated with
normal and/or pathological ageing. While perturbations in collagen homeostasis,
trafficking of toll-like receptors and endosomal pathways were commonly
identified, degradation of insulin-like growth factor-binding proteins was
uniquely identified in pathological ageing.
PMID- 26431328
TI - Caspase 3 in dying tumor cells mediates post-irradiation angiogenesis.
AB - Cytotoxic radiotherapy unfavorably induces tumor cells to generate various
proangiogenic substances, promoting post-irradiation angiogenesis (PIA), which is
one of major causes of radiotherapy failure. Though several studies have reported
some mechanisms behind PIA, they have not yet described the beginning
proangiogenic motivator buried in the irradiated microenvironment. In this work,
we revealed that dying tumor cells induced by irradiation prompted PIA via a
caspase 3 dependent mechanism. Proteolytic inactivation of caspase 3 in dying
tumor cells by transducing a dominant-negative version weakened proangiogenic
effects in vitro and in vivo. In addition, inhibition of caspase 3 activity
suppressed tumor angiogenesis and tumorigenesis in xenograft mouse model.
Importantly, we identified vascular endothelial growth factor (VEGF)-A as a
downstream proangiogenic factor regulated by caspase 3 possibly through Akt
signaling. Collectively, these findings indicated that besides acting as a key
executioner in apoptosis, caspase 3 in dying tumor cells may play a central role
in driving proangiogenic response after irradiation. Thus, radiotherapy in
combination with caspase 3 inhibitors may be a novel promising therapeutic
strategy to reduce tumor recurrence due to restrained PIA.
PMID- 26431330
TI - Subcellular localization of PUMA regulates its pro-apoptotic activity in
Burkitt's lymphoma B cells.
AB - The BH3-only protein PUMA (p53-upregulated modulator of apoptosis) is a major
regulator of apoptosis. It belongs to the Bcl-2 family of proteins responsible
for maintaining mitochondrial outer membrane integrity by controlling the
intrinsic (mitochondrial) apoptotic pathway. We describe here a new pathway
regulating PUMA activation through the control of its subcellular distribution.
Surprisingly, neither PUMA upregulation in normal activated human B lymphocytes
nor high levels of PUMA in Burkitt's lymphoma (BL) were associated with cell
death. We show that PUMA is localized to the cytosol in these cells. By contrast,
various apoptosis-triggering signals were found to promote the translocation of
PUMA to the mitochondria in these cells, leading to their death by apoptosis.
This apoptosis was associated with the binding of mitochondrial PUMA to anti
apoptotic members of the Bcl-2 family, such as Bcl-2 and Mcl-1. This
translocation was caspase-independent but was prevented by inhibiting or knocking
down the expression of the MAPK kinase p38. Our data suggest that the
accumulation of PUMA in the cytosol may be important for the participation of
this protein in apoptosis without the need for prior transcription. This
regulatory pathway may be an important feature of differentiation and tumorigenic
processes.
PMID- 26431329
TI - DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage
of inflamm-aging.
AB - A major issue in aging research is how cellular phenomena affect aging at the
systemic level. Emerging evidence suggests that DNA damage response (DDR)
signaling is a key mechanism linking DNA damage accumulation, cell senescence,
and organism aging. DDR activation in senescent cells promotes acquisition of a
proinflammatory secretory phenotype (SASP), which in turn elicits DDR and SASP
activation in neighboring cells, thereby creating a proinflammatory environment
extending at the local and eventually the systemic level. DDR activation is
triggered by genomic lesions as well as emerging bacterial and viral metagenomes.
Therefore, the buildup of cells with an activated DDR probably fuels inflamm
aging and predisposes to the development of the major age-related diseases
(ARDs). Micro (mi)-RNAs - non-coding RNAs involved in gene expression modulation
are released locally and systemically by a variety of shuttles (exosomes,
lipoproteins, proteins) that likely affect the efficiency of their biological
effects. Here we suggest that some miRNAs, previously found to be associated with
inflammation and senescence - miR-146, miR-155, and miR-21 - play a central role
in the interplay among DDR, cell senescence and inflamm-aging. The identification
of the functions of shuttled senescence-associated miRNAs is expected to shed
light on the aging process and on how to delay ARD development.
PMID- 26431331
TI - 18F-EF5 PET Is Predictive of Response to Fractionated Radiotherapy in Preclinical
Tumor Models.
AB - We evaluated the relationship between pre-treatment positron emission tomography
(PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-
pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor
models to a range of fractionated radiotherapies. Subcutaneous HT29, A549 and RKO
tumors grown in nude mice were imaged using 18F-EF5 positron emission tomography
(PET) in order to characterize the extent and heterogeneity of hypoxia in these
systems. Based on these results, 80 A549 tumors were subsequently grown and
imaged using 18F-EF5 PET, and then treated with one, two, or four fraction
radiation treatments to a total dose of 10-40 Gy. Response was monitored by
serial caliper measurements of tumor volume. Longitudinal post-treatment 18F-EF5
PET imaging was performed on a subset of tumors. Terminal histologic analysis was
performed to validate 18F-EF5 PET measures of hypoxia. EF5-positive tumors
responded more poorly to low dose single fraction irradiation relative to EF5
negative tumors, however both groups responded similarly to larger single
fraction doses. Irradiated tumors exhibited reduced 18F-EF5 uptake one month
after treatment compared to control tumors. These findings indicate that pre-
treatment 18F-EF5 PET can predict the response of tumors to single fraction
radiation treatment. However, increasing the number of fractions delivered
abrogates the difference in response between tumors with high and low EF5 uptake
pre-treatment, in agreement with traditional radiobiology.
PMID- 26431334
TI - Correction: Engraftment of Human Glioblastoma Cells in Immunocompetent Rats
through Acquired Immunosuppression.
PMID- 26431332
TI - Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus
Infection in Epithelial Cells.
AB - Epstein-Barr virus (EBV) is a human herpesvirus associated with B-cell and
epithelial cell malignancies. EBV lytically infects normal differentiated oral
epithelial cells, where it causes a tongue lesion known as oral hairy leukoplakia
(OHL) in immunosuppressed patients. However, the cellular mechanism(s) that
enable EBV to establish exclusively lytic infection in normal differentiated oral
epithelial cells are not currently understood. Here we show that a cellular
transcription factor known to promote epithelial cell differentiation, KLF4,
induces differentiation-dependent lytic EBV infection by binding to and
activating the two EBV immediate-early gene (BZLF1 and BRLF1) promoters. We
demonstrate that latently EBV-infected, telomerase-immortalized normal oral
keratinocyte (NOKs) cells undergo lytic viral reactivation confined to the more
differentiated cell layers in organotypic raft culture. Furthermore, we show that
endogenous KLF4 expression is required for efficient lytic viral reactivation in
response to phorbol ester and sodium butyrate treatment in several different EBV
infected epithelial cell lines, and that the combination of KLF4 and another
differentiation-dependent cellular transcription factor, BLIMP1, is highly
synergistic for inducing lytic EBV infection. We confirm that both KLF4 and
BLIMP1 are expressed in differentiated, but not undifferentiated, epithelial
cells in normal tongue tissue, and show that KLF4 and BLIMP1 are both expressed
in a patient-derived OHL lesion. In contrast, KLF4 protein is not detectably
expressed in B cells, where EBV normally enters latent infection, although KLF4
over-expression is sufficient to induce lytic EBV reactivation in Burkitt
lymphoma cells. Thus, KLF4, together with BLIMP1, plays a critical role in
mediating lytic EBV reactivation in epithelial cells.
PMID- 26431333
TI - Functional Brain Dysfunction in Patients with Benign Childhood Epilepsy as
Revealed by Graph Theory.
AB - There is growing evidence that brain networks are altered in epileptic subjects.
In this study, we investigated the functional connectivity and brain network
properties of benign childhood epilepsy with centrotemporal spikes using graph
theory. Benign childhood epilepsy with centrotemporal spikes is the most common
form of idiopathic epilepsy in young children under the age of 16 years. High
density EEG data were recorded from patients and controls in resting state with
eyes closed. Data were preprocessed and spike and spike-free segments were
selected for analysis. Phase locking value was calculated for all paired
combinations of channels and for five frequency bands (delta, theta, alpha, beta1
and beta2). We computed the degree and small-world parameters--clustering
coefficient (C) and path length (L)--and compared the two patient conditions to
controls. A higher degree at epileptic zones during interictal epileptic spikes
(IES) was observed in all frequency bands. Both patient conditions reduced
connection at the occipital and right frontal regions close to the epileptic zone
in the alpha band. The "small-world" features (high C and short L) were deviated
in patients compared to controls. A changed from an ordered network in the delta
band to a more randomly organized network in the alpha band was observed in
patients compared to healthy controls. These findings show that the benign
epileptic brain network is disrupted not only at the epileptic zone, but also in
other brain regions especially frontal regions.
PMID- 26431335
TI - Hyperglycemic Stress Impairs the Stemness Capacity of Kidney Stem Cells in Rats.
AB - The incidence of acute kidney injury in patients with diabetes is significantly
higher than that of patients without diabetes, and may be associated with the
poor stemness capacity of kidney stem cells (KSCs) and limited recovery of
injured renal tubules. To investigate the effects of hyperglycemic stress on KSC
stemness, KSCs were isolated from the rat renal papilla and analyzed for their
self-renewal and differentiation abilities. Our results showed that isolated KSCs
expressed the mesenchymal stem cell markers N-cadherin, Nestin, CD133, CD29,
CD90, and CD73. Moreover, KSCs co-cultured with hypoxia-injured renal tubular
epithelial cell (RTECs) induced the expression of the mature epithelial cell
marker CK18, suggesting that the KSCs could differentiate into RTECs in vitro.
However, KSC proliferation, differentiation ability and tolerance to hypoxia were
decreased in high-glucose cultures. Taken together, these results suggest the
high-glucose microenvironment can damage the reparative ability of KSCs. It may
result in a decreased of recovery capability of renal tubules from injury.
PMID- 26431336
TI - Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth
Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh.
AB - Prenatal multiple micronutrient (MM) supplementation improves birth weight
through increased fetal growth and gestational age, but whether maternal or fetal
growth factors are involved is unclear. Our objective was to examine the effect
of prenatal MM supplementation on intrauterine growth factors and the
associations between growth factors and birth outcomes in a rural setting in
Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs.
iron and folic acid (IFA) supplementation, we measured placental growth hormone
(PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks
gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1
(IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size
and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5
(2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on
concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1.
However, among pregnancies of female offspring, hPL concentration was higher by
1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for
interaction); and among women with height <145 cm, insulin was higher by 59% (95%
CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and
cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively,
associated with birth weight z score and other measures of birth size (all
p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other
growth factors were not associated with gestational age or preterm birth.
Prenatal MM supplementation had no overall impact on intrauterine growth factors.
MM supplementation altered some growth factors differentially by maternal early
pregnancy nutritional status and sex of the offspring, but this should be
examined in other studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00860470.
PMID- 26431337
TI - A Curated Database of Rodent Uterotrophic Bioactivity.
AB - BACKGROUND: Novel in vitro methods are being developed to identify chemicals that
may interfere with estrogen receptor (ER) signaling, but the results are
difficult to put into biological context because of reliance on reference
chemicals established using results from other in vitro assays and because of the
lack of high-quality in vivo reference data. The Organisation for Economic Co
operation and Development (OECD)-validated rodent uterotrophic bioassay is
considered the "gold standard" for identifying potential ER agonists. OBJECTIVES:
We performed a comprehensive literature review to identify and evaluate data from
uterotrophic studies and to analyze study variability. METHODS: We reviewed 670
articles with results from 2,615 uterotrophic bioassays using 235 unique
chemicals. Study descriptors, such as species/strain, route of administration,
dosing regimen, lowest effect level, and test outcome, were captured in a
database of uterotrophic results. Studies were assessed for adherence to six
criteria that were based on uterotrophic regulatory test guidelines. Studies
meeting all six criteria (458 bioassays on 118 unique chemicals) were considered
guideline-like (GL) and were subsequently analyzed. RESULTS: The immature rat
model was used for 76% of the GL studies. Active outcomes were more prevalent
across rat models (74% active) than across mouse models (36% active). Of the 70
chemicals with at least two GL studies, 18 (26%) had discordant outcomes and were
classified as both active and inactive. Many discordant results were attributable
to differences in study design (e.g., injection vs. oral dosing). CONCLUSIONS:
This uterotrophic database provides a valuable resource for understanding in vivo
outcome variability and for evaluating the performance of in vitro assays that
measure estrogenic activity. CITATION: Kleinstreuer NC, Ceger PC, Allen DG,
Strickland J, Chang X, Hamm JT, Casey WM. 2016. A curated database of rodent
uterotrophic bioactivity. Environ Health Perspect 124:556-562;
http://dx.doi.org/10.1289/ehp.1510183.
PMID- 26431338
TI - Whole Blood Transcriptome Analysis of Mycoplasma mycoides Subsp. mycoides
Infected Cattle Confirms Immunosuppression but Does Not Reflect Local
Inflammation.
AB - Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp.
mycoides (Mmm), is a severe respiratory disease of cattle responsible for major
economic losses in sub-Saharan Africa. Disease control relies mainly on the use
of empirically attenuated vaccines that provide limited protection. Thus,
understanding the virulence mechanisms used by Mmm as well as the role of the
host immune system in disease development, persistence, and control is a
prerequisite for the development of new, rationally designed control strategies.
The aim of this study was to assess the use of whole blood transcriptome analysis
to study cattle-Mmm interactions, starting by the characterization of the bovine
response to Mmm infection during the acute form of the disease. For that purpose,
we compared the transcriptome profile of whole blood from six cattle, before
challenge by contact with Mmm-infected animals and at the appearance of first
clinical signs, using a bovine microarray. Functional analysis revealed that 680
annotated genes were differentially expressed, with an overwhelming majority of
down-regulated genes characterizing an immunosuppression. The main bio-functions
affected were "organismal survival", "cellular development, morphology and
functions" and "cell-to cell signaling and interactions". These affected
functions were consistent with the results of previous in vitro immunological
studies. However, microarray and qPCR validation results did not highlight pro
inflammatory molecules (such as TNFalpha, TLR2, IL-12B and IL-6), whereas
inflammation is one of the most characteristic traits of acute CBPP. This global
gene expression pattern may be considered as the result, in blood, of the local
pulmonary response and the systemic events occurring during acute CBPP.
Nevertheless, to understand the immune events occurring during disease, detailed
analyses on the different immune cell subpopulations, either in vivo, at the
local site, or in vitro, will be required. Whole blood transcriptome analysis
remains an interesting approach for the identification of bio-signatures
correlating to recovery and protection, which should facilitate the evaluation
and validation of novel vaccine formulations.
PMID- 26431339
TI - Development of Physiologically Based Pharmacokinetic/Pharmacodynamic Model for
Indomethacin Disposition in Pregnancy.
AB - Findings of a recent clinical study showed indomethacin has lower plasma levels
and higher steady-state apparent clearance in pregnant subjects when compared to
those in non-pregnant subjects reported in separate studies. Thus, in the current
work we developed a pregnancy physiological based pharmacokinetic/pharmacodynamic
(PBPK/PD) model for indomethacin to explain the differences in indomethacin
pharmacokinetics between pregnancy and non-pregnancy. A whole-body PBPK model
with key pregnancy-related physiological changes was developed to characterize
indomethacin PK in pregnant women and compare these parameters to those in non
pregnant subjects. Data related to maternal physiological and biological changes
were obtained from literature and incorporated into the structural PBPK model
that describes non-pregnant PK data. Changes in indomethacin area under the curve
(AUC), maximum concentration (Cmax) and average steady-state concentration (Cave)
in pregnant women were predicted. Model-simulated PK profiles were in agreement
with observed data. The predicted mean ratio (non-pregnant:second trimester (T2))
of indomethacin Cave was 1.6 compared to the observed value of 1.59. In addition,
the predicted steady-state apparent clearance (CL/Fss) ratio was almost similar
to the observed value (0.46 vs. 0.42). Sensitivity analysis suggested changes in
CYP2C9 activity, and to a lesser extent UGT2B7, as the primary factor
contributing to differences in indomethacin disposition between pregnancy and non
pregnancy. The developed PBPK model which integrates prior physiological
knowledge, in vitro and in vivo data, allowed the successful prediction of
indomethacin disposition during T2. Our PBPK/PD model suggested a higher
indomethacin dosing requirement during pregnancy.
PMID- 26431340
TI - Modeling and Implementation of Cattle/Beef Supply Chain Traceability Using a
Distributed RFID-Based Framework in China.
AB - In recent years, traceability systems have been developed as effective tools for
improving the transparency of supply chains, thereby guaranteeing the quality and
safety of food products. In this study, we proposed a cattle/beef supply chain
traceability model and a traceability system based on radio frequency
identification (RFID) technology and the EPCglobal network. First of all, the
transformations of traceability units were defined and analyzed throughout the
cattle/beef chain. Secondly, we described the internal and external traceability
information acquisition, transformation, and transmission processes throughout
the beef supply chain in detail, and explained a methodology for modeling
traceability information using the electronic product code information service
(EPCIS) framework. Then, the traceability system was implemented based on
Fosstrak and FreePastry software packages, and animal ear tag code and electronic
product code (EPC) were employed to identify traceability units. Finally, a
cattle/beef supply chain included breeding business, slaughter and processing
business, distribution business and sales outlet was used as a case study to
evaluate the beef supply chain traceability system. The results demonstrated that
the major advantages of the traceability system are the effective sharing of
information among business and the gapless traceability of the cattle/beef supply
chain.
PMID- 26431341
TI - Risk Factors for Sporadic Domestically Acquired Campylobacter Infections in
Norway 2010-2011: A National Prospective Case-Control Study.
AB - BACKGROUND: Campylobacteriosis is the most frequently reported food- and
waterborne infection in Norway. We investigated the risk factors for sporadic
Campylobacter infections in Norway in order to identify areas where control and
prevention measures could be improved. METHODS: A national prospective case
control study of factors associated with Campylobacter infection was conducted
from July 2010 to September 2011. Cases were recruited from the Norwegian
Surveillance System of Communicable Diseases (MSIS). Controls were randomly
selected from the Norwegian Population Registry. Cases and controls were mailed a
paper questionnaire with a prepaid return envelope. Univariable analyses using
logistic regression were conducted for all exposures. A final parsimonious
multivariable model was developed using regularized/penalized logistic
regression, and adjusted odds ratios were calculated. RESULTS: A total of 995
cases and 1501 controls were included in the study (response proportion 55% and
30%, respectively). Exposures that had significant increases in odds of
Campylobacter infection in multivariable analysis were drinking water directly
from river, stream, or lake (OR: 2.96), drinking purchased bottled water (OR:
1.78), eating chicken (1.69), eating meat that was undercooked (OR: 1.77), eating
food made on a barbecue (OR: 1.55), living on a farm with livestock (OR: 1.74),
having a dog in the household (OR: 1.39), and having household water supply
serving fewer than 20 houses (OR: 1.92). CONCLUSIONS: Consumption of poultry and
untreated water remain important sources of Campylobacter infection in Norway,
despite ongoing control efforts. The results justify the need for strengthening
education for consumers and food handlers about the risks of cross-contamination
when preparing poultry and with consuming raw or undercooked chicken. The public
should also be reminded to take precautions when drinking untreated water in
nature and ensure continued vigilance in order to protect and maintain the
quality of water from small-scale water supply systems.
PMID- 26431343
TI - The Effect of Preserved Residual Renal Function on Left Ventricular Structure in
Non-Anuric Peritoneal Dialysis Patients.
AB - BACKGROUND/AIMS: Residual renal function (RRF) has been shown to influence
survival of peritoneal dialysis (PD) patients. This study examined the relations
between RRF and left ventricular hypertrophy (LVH) before switching on dialysis
treatment and observed during 18 months on PD treatment. METHODS: A prospective
longitudinal study was performed in 50 non-anuric (defined as >200 mL urine
output in a 24-hour period) PD patients. Echocardiography, RRF and other known
risk factors for the increase of LV mass index (LVMi) were determined at study
baseline and the end of follow-up. RESULTS: There was 78% patients with LVH in
end-stage renal disease (ESRD) baseline and 60% at the end of follow-up. RRF at
the start of the study showed no significant difference between patients with
normal and increased LVMi, as well as in daily collection of urine. After 18
months, patients with decreased LVMi had better RRF, lower CRP and better Kt/V
compared to patients with increased LVMi (p < 0.001). Patients with better
preserved RRF not only had significantly higher total Kt/V, but were less anemic
and hypoproteinemic and lesser presence of LVH. CONCLUSIONS: PD in non-anuric
ESRD patients the first 18 months has a positive effect on the preservation of
RRF and partial regression of left ventricular remodeling.
PMID- 26431342
TI - Cancer statistics: Breast cancer in situ.
AB - An estimated 60,290 new cases of breast carcinoma in situ are expected to be
diagnosed in 2015, and approximately 1 in 33 women is likely to receive an in
situ breast cancer diagnosis in her lifetime. Although in situ breast cancers are
relatively common, their clinical significance and optimal treatment are topics
of uncertainty and concern for both patients and clinicians. In this article, the
American Cancer Society provides information about occurrence and treatment
patterns for the 2 major subtypes of in situ breast cancer in the United States
ductal carcinoma in situ and lobular carcinoma in situ-using data from the North
American Association of Central Cancer Registries and the 13 oldest Surveillance,
Epidemiology, and End Results registries. The authors also present an overview of
in situ breast cancer detection, treatment, risk factors, and prevention and
discuss research needs and initiatives.
PMID- 26431344
TI - Sympathetic Neurotransmitters Modulate Osteoclastogenesis and Osteoclast Activity
in the Context of Collagen-Induced Arthritis.
AB - Excessive synovial osteoclastogenesis is a hallmark of rheumatoid arthritis (RA).
Concomitantly, local synovial changes comprise neuronal components of the
peripheral sympathetic nervous system. Here, we wanted to analyze if collagen
induced arthritis (CIA) alters bone marrow-derived macrophage (BMM)
osteoclastogenesis and osteoclast activity, and how sympathetic neurotransmitters
participate in this process. Therefore, BMMs from Dark Agouti rats at different
CIA stages were differentiated into osteoclasts in vitro and osteoclast number,
cathepsin K activity, matrix resorption and apoptosis were analyzed in the
presence of acetylcholine (ACh), noradrenaline (NA) vasoactive intestinal peptide
(VIP) and assay-dependent, adenylyl cyclase activator NKH477. We observed
modulation of neurotransmitter receptor mRNA expression in CIA osteoclasts
without affecting protein level. CIA stage-dependently altered marker gene
expression associated with osteoclast differentiation and activity without
affecting osteoclast number or activity. Neurotransmitter stimulation modulated
osteoclast differentiation, apoptosis and activity. VIP, NA and adenylyl cyclase
activator NKH477 inhibited cathepsin K activity and osteoclastogenesis (NKH477,
10(-6) M NA) whereas ACh mostly acted pro-osteoclastogenic. We conclude that CIA
alone does not affect metabolism of in vitro generated osteoclasts whereas
stimulation with NA, VIP plus specific activation of adenylyl cyclase induced
anti-resorptive effects probably mediated via cAMP signaling. Contrary, we
suggest pro-osteoclastogenic and pro-resorptive properties of ACh mediated via
muscarinic receptors.
PMID- 26431345
TI - Ovarian granulosa cell tumour and letrozole: A case report.
PMID- 26431347
TI - A Simple Chiral Cu(II) Complex as an Effective Phase-Transfer Catalyst for the
Enantioselective Alkylation of Dissymmetric Glycinate Ketimines.
AB - Catalytic asymmetric benzylation of a dissymmetric tert-butylglycinate ketimine,
incorporating 1-naphthyl and phenyl groups as the Schiff base substituents, under
phase-transfer conditions was investigated. It was interesting to note that the
sense of asymmetric induction of the alkylation of Z-imine stereoisomer is
opposite to that of the corresponding E stereoisomer with a similar degree of
enantioselectivity. More interestingly, the chiral Cu(II) complex of the Schiff
base derived from (R)-2-phenylglycinol and 2-hydroxy-1-naphthaldehyde was found
to catalyze the same reaction under solid-liquid conditions with comparable
enantioselectivity (up to 60% ee) with respect to known cinchona alkaloid
catalysts. The solvent/base-system parameter was shown to control the optimal
catalytic activity.
PMID- 26431346
TI - Risk Factors for Central Lymph Node Metastasis in CN0 Papillary Thyroid
Carcinoma: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Central lymph node metastasis (CLNM) is common in papillary thyroid
carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) for patients
with clinically negative central compartment lymph nodes (CN0) remains
controversial. The phrase "clinically negative" is used to indicate that patients
exhibited no clinical evidence of CLNM by ultrasonography (US) or computerized
tomography (CT) preoperatively. In this study, we analyze the risk factors for
CLNM in CN0 patients. METHODS: The PUBMED and SCIE databases were systematically
searched for works published through January 31, 2015. All of the patients
included in this study underwent thyroidectomy+PCLND. Revman 5.3 software was
used to analyze the data. RESULTS: Twenty studies and 9084 patients were included
in this meta-analysis. The following variables were associated with an increased
risk of CLNM in CN0 patients: age < 45 years (OR = 1.59, 95% CI = 1.42-1.78,
p<0.00001), male sex (OR = 1.95, 95% CI = 1.63-2.32, p<0.00001), multifocality
(OR = 1.43, 95% CI = 1.22-1.67, p<0.00001), tumor size > 2 cm for PTC patients
(OR = 2.98, 95% CI 2.08-4.28, p<0.00001) or tumor size > 0.5 cm for papillary
thyroid microcarcinoma (PTMC) patients (OR = 2.30, 95% CI = 1.71-3.09,
p<0.00001), location of the primary tumor in the central area and low pole (OR =
1.86, 95% CI = 1.48-2.33, p<0.00001), lymphovascular invasion (OR = 4.35, 95% CI
= 2.24-8.46, p<0.0001), extrathyroidal extension (OR = 2.27, 95% CI = 1.76-2.94,
p<0.00001), and capsular invasion (OR = 1.72, 95% CI = 1.39-2.41, p<0.00001). PTC
(tumor size > 1 cm) exhibited a higher risk factor associated with CLNM than PTMC
(tumor size < 1 cm) (OR = 2.83, 95% CI = 2.15-3.72, p<0.00001). Bilateral tumors
(OR = 1.21, 95% CI = 0.92-1.58, p = 0.17) and lymphocytic thyroiditis (OR = 0.88,
95% CI = 0.71-1.09, p = 0.25) had no association with CLNM in CN0 patients.
CONCLUSIONS: Our systematic review identified several clinical features
associated with CLNM in CN0 patients, including age, sex, multifocality, size,
location, lymphovascular invasion, capsular invasion, and extrathyroidal
extension. These factors should guide the application of PCLND in CN0 patients.
PMID- 26431348
TI - Anti-Inflamm-Aging Effects of Long-Term Caloric Restriction via Overexpression of
SIGIRR to Inhibit NF-kappaB Signaling Pathway.
AB - BACKGROUND: Chronic inflammation is thought to be a determinant of the aging rate
and longevity. Caloric restriction (CR) attenuates age-related increases in the
systemic levels of several pro-inflammatory mediators, but the anti-inflammatory
mechanisms of CR in the aging process remain unclear. METHODS: Fisher 344 rats in
a CR group were fed an amount of food corresponding to 60% of that fed to an ad
libitum-fed (AL) group for 8 months. Biochemical analyses and renal pathological
grading were used to analyze physiological status. Important signaling molecules
in the Toll-like receptor/nuclear factor kappa-light-chain-enhancer of activated
B cells (TLR/NF-kappaB) pathway were also analyzed by western blotting,
immunofluorescence and immunohistochemistry. RESULTS: 1) Compared with AL
feeding, CR decreased aging-mediated increases in both biochemical marker levels
and renal pathological grading. 2) Single immunoglobulin IL-1 (IL-1)-related
receptor (SIGIRR) expression decreased with increasing age, but CR led to
overexpression. 3) The expression of TLR4 was significantly higher in the CR
group than in the AL group. 4) SIGIRR overexpression decreased the expression of
the adaptor molecules myeloid differentiation factor 88 (MyD88), IL-1 receptor
associated kinase 4 (IRAK4) and tumor necrosis factor receptor-associated factor
6 (TRAF6). 5) The levels of the inflammatory markers phospho-IkappaBalpha and
phospho-NF-kappaB p65 decreased in the CR group. CONCLUSIONS: The inflammatory
response might be alleviated by SIGIRR via blockade of the TLR4/NF-kappaB
signaling pathway. Therefore, CR can decrease inflammation via SIGIRR
overexpression, and SIGIRR might be a new target to delay aging.
PMID- 26431349
TI - An amorphous CoSe film behaves as an active and stable full water-splitting
electrocatalyst under strongly alkaline conditions.
AB - It is attractive but still remains a big challenge to develop non-noble metal
bifunctional electrocatalysts efficient for both oxygen evolution reaction (OER)
and hydrogen evolution reaction (HER) under alkaline conditions. Herein, an
amorphous CoSe film electrodeposited on a Ti mesh (a-CoSe/Ti) is demonstrated to
exhibit high electrocatalytic activity and stability for both reactions in 1.0 M
KOH. It needs overpotentials of 292 and 121 mV to drive 10 mA cm(-2) for OER and
HER, respectively. The two-electrode alkaline water electrolyzer affords a water
splitting current of 10 mA cm(-2) at a cell voltage of 1.65 V. This work offers
an attractive cost-effective catalytic material toward full water splitting
applications.
PMID- 26431350
TI - 'What do you think?' the collaborative practices of choice and care in a Danish
obstetric ultrasound unit.
AB - This paper is based on ethnographic fieldwork at an obstetric ultrasound unit in
Denmark and explores the few, intense minutes of clinical interaction following a
high-risk screening result for Down's syndrome. The category of high-risk
transforms the routine ultrasound into a situation of inescapable choice, where
the health of the foetus is questioned and decisions must be made. The clinical
interactions following a high-risk result are investigated as processes of
production, and the concepts of logic of choice and the logic of care are
employed as analytical tools for identifying different rationales at play in the
situation. The analysis shows that sonographers and women/couples collaboratively
engage in logics of choice and care. Their mutual aim is to make the high-risk
results meaningful and manageable so that a decision can be made. In this process
initiative is shifted back and forth. Through a logic of care, complexity is
reduced and statistics transformed by emphasising certain interpretations and
leaving others unspoken. However, the logic of choice is also collectively
maintained by positioning the women/couples as decision-makers. It is argued that
in the obstetric ultrasound unit, the logic of choice provides a powerful frame,
with the logic of care filling in the gaps and discontinuities to facilitate
decisions. In this context, the logics are complementary rather than competing,
and thus the analysis add new perspectives to the original concepts. In sum, the
logics of choice and care provide a valuable analytical tool for interpreting and
understanding the complex and collaborative practices of clinical interaction.
PMID- 26431351
TI - Differences in Outcomes in Prenatally Diagnosed Congenital Diaphragmatic Hernia
Compared to Postnatal Detection: A Single-Center Experience.
AB - OBJECTIVES: To compare outcomes in pregnancies with a prenatal detection of
congenital diaphragmatic hernia (CDH) with children diagnosed after birth,
treated at the same institution, and to determine the ability to predict
prognosis through measurements of the observed to expected lung-to-head ratio
(O/E LHR). METHODS: This is a retrospective review of all children with CDH
treated at our institution during 2006-2014. We compared outcomes of infants
referred for surgery after postnatal diagnosis with outcomes of infants with
prenatally diagnosed CDH. RESULTS: In the prenatal group, O/E LHR was
significantly different between survivors and deceased patients, with a cutoff at
35% O/E LHR. Survival to discharge and 1-year survival were significantly higher
in the postnatal group that required intubation within 24 h; i.e., 92 and 89%
versus 85 and 73% in the prenatal group (p < 0.05). There was less need for
extracorporeal membrane oxygenation (ECMO), 41 versus 60%, and patch, 41 versus
75% (p < 0.001), in the postnatal group with early diagnosis compared with the
prenatal group, respectively. CONCLUSION: Children with prenatally diagnosed CDH
represent a population with a more severe condition compared to infants diagnosed
after birth. They have poorer outcomes with higher needs for ECMO or use of
patch, and lower survival rates were observed at an O/E LHR below 35%.
PMID- 26431352
TI - Performance of Four Transport and Storage Systems for Molecular Detection of
Multidrug-Resistant Tuberculosis.
AB - BACKGROUND: Detection of drug-resistant tuberculosis is essential for the control
of the disease but it is often hampered by the limitation of transport and
storage of samples from remote locations to the reference laboratory. We
performed a retrospective field study to evaluate the performance of four
supports enabling the transport and storage of samples to be used for molecular
detection of drug resistance using the GenoType MTBDRplus. METHODS: Two hundred
Mycobacterium tuberculosis strains were selected and spotted on slides, FTA
cards, GenoCards, and in ethanol. GenoType MTBDRplus was subsequently performed
with the DNA extracted from these supports. Sensitivity and specificity were
calculated and compared to the results obtained by drug susceptibility testing.
RESULTS: For all supports, the overall sensitivity and specificity for detection
of resistance to RIF was between 95% and 100%, and for INH between 95% and 98%.
CONCLUSION: The four transport and storage supports showed a good sensitivity and
specificity for the detection of resistance to RIF and INH in M. tuberculosis
strains using the GenoType MTBDRplus. These supports can be maintained at room
temperature and could represent an important alternative cost-effective method
useful for rapid molecular detection of drug-resistant TB in low-resource
settings.
PMID- 26431353
TI - Effects of Maternal Exposure to Piperonyl Butoxide (PBO) on Behavioral
Development in F1-Generation Mice.
AB - Female mice were exposed maternally to piperonyl butoxide (PBO) through diet to
provide dietary levels of 0% (control), 0.01%, 0.03%, and 0.09% during gestation
and lactation periods, and selected reproductive and neurobehavioral parameters
were measured in the F1 generation. There was no adverse effect of PBO on litter
size, litter weight, or sex ratio at birth. The average body weights of male
offspring decreased significantly in dose-related manners on postnatal days
(PNDs) 0, 4, 7, and 14 (p = 0.0019, 0.0096, 0.033, and 0.038, respectively)
during the lactation period. In female offspring, the average body weights
decreased in dose-related manners on PNDs 0, 4, 7, and 14 (p = 0.0027, 0.0104,
0.0193, and 0.0062, respectively). The survival of dams slightly decreased (p =
0.0209) in the high-dose group during the lactation period. With respect to
behavioral developmental parameters, surface righting on PND 7 of male and female
offspring was delayed significantly in a dose-related manner (p < 0.001 in each).
Swimming direction on PND 7 of male offspring was delayed significantly in a dose
related manner (p < 0.01), and for female offspring it was delayed significantly
in the high-dose group (p < 0.05). Swimming head angle on PND 7 of male offspring
was delayed significantly in a dose-related manner (p < 0.05). Spontaneous
behavior examination in males indicated that rearing increased in the high-dose
group in the F1 generation. The dose levels of PBO in the present study produced
some adverse effects in neurobehavioral parameters in mice.
PMID- 26431358
TI - Generation and preclinical characterization of an antibody specific for SEMA4D.
AB - Semaphorin 4D (SEMA4D or CD100) is a member of the semaphorin family of proteins
and an important mediator of the movement and differentiation of multiple cell
types, including those of the immune, vascular, and nervous systems. Blocking the
binding of SEMA4D to its receptors can result in physiologic changes that may
have implications in cancer, autoimmune, and neurological disease. To study the
effects of blocking SEMA4D, we generated, in SEMA4D-deficient mice, a panel of
SEMA4D-specific hybridomas that react with murine, primate, and human SEMA4D.
Utilizing the complementarity-determining regions from one of these hybridomas
(mAb 67-2), we generated VX15/2503, a humanized IgG4 monoclonal antibody that is
currently in clinical development for the potential treatment of various
malignancies and neurodegenerative disorders, including multiple sclerosis and
Huntington's disease. This work describes the generation and characterization of
VX15/2503, including in vitro functional testing, epitope mapping, and an in vivo
demonstration of efficacy in an animal model of rheumatoid arthritis.
PMID- 26431359
TI - TGF-beta3 and IGF-1 synergy ameliorates nucleus pulposus mesenchymal stem cell
differentiation towards the nucleus pulposus cell type through MAPK/ERK
signaling.
AB - This study aimed to investigate the synergy between transforming growth factor
beta 3 (TGF-beta3) and insulin-like growth factor 1 (IGF-1) on nucleus pulposus
derived mesenchymal stem cells (NP-MSCs) and the underlying mechanism using a
serum-free culture system. NP-MSC proliferation and viability were measured using
a CCK-8 assay and annexin V-FITC/propidium iodide, respectively. NP-MSCs in
micromasses were investigated for differentiation towards nucleus pulposus cells
(NPCs). SOX-9, collagen-I, collagen-II, aggrecan and decorin expressions were
detected by RT-PCR and immunoblotting. Matrix deposition was assessed by sulfated
glycosaminoglycan (sGAG) analysis. Novel chondrogenic and nucleus pulposus (NP)
genes were detected to distinguish differentiated cell types. MAPK/ERK and
TGF/Smad signaling pathways were also examined. As a result, the synergy between
TGF-beta3 and IGF-1 enhanced NP-MSC viability, extracellular matrix (ECM)
biosynthesis and differentiation towards NPCs, partly through the activation of
the MAPK/ERK signaling pathway. Therefore, the synergy between TGF-beta3 and IGF
1 ameliorates NP-MSC viability, differentiation and promotes intervertebral disc
regeneration.
PMID- 26431365
TI - Adding transcutaneous electrical nerve stimulation to visual scanning training
does not enhance treatment effect on hemispatial neglect: a randomized,
controlled, double-blind study.
AB - BACKGROUND: Left-sided transcutaneous electrical nerve stimulation (TENS)
increases right hemispheric activity, which may improve the rehabilitative
outcome of hemispatial neglect. OBJECTIVE: To examine the behavioral effect of
electrical stimulation of the nerve afferents of the left hand during early
neuropsychological rehabilitation of post-stroke patients with hemispatial
neglect. METHODS: This randomized, controlled, double-blind study included 29
patients (enrolled in the experimental or control group) with left hemispatial
neglect after right hemispheric stroke. For 3 weeks, patients received 15
therapeutic sessions involving TENS (active or sham) with a mesh glove applied on
the entire left hand during the first 30 minutes of a 45-minute conventional
visual scanning training (VST). Signs of hemispatial neglect were assessed using
a psychometric test before and after treatment. RESULTS: Univariate analysis of
covariance revealed that differences between the control and experimental groups
were not significant after treatment (F(1, 22) = 0.294, P = 0.593) when adjusted
for pre-treatment scores and time since stroke onset. This suggested that
electrical stimulation failed to mitigate the severity of hemispatial neglect
symptoms. CONCLUSION: Our study did not provide evidence of the effectiveness of
TENS when added to VST during early rehabilitation for patients with post-stroke
hemispatial neglect. Other techniques (applied alone or together) should be
sought to improve recovery in this population.
PMID- 26431367
TI - Attenuating microwave radiation by absorption through controlled nanoparticle
localization in PC/PVDF blends.
AB - Nanoscale ordering in a polymer blend structure is indispensable to obtain
materials with tailored properties. It was established here that controlling the
arrangement of nanoparticles, with different characteristics, in co-continuous
PC/PVDF (polycarbonate/poly(vinylidene fluoride)) blends can result in
outstanding microwave absorption (ca. 90%). An excellent reflection loss (RL) of
ca. -71 dB was obtained for a model blend structure wherein the conducting
(multiwall carbon nanotubes, MWNTs) and the magnetic inclusions (Fe3O4) are
localized in PVDF and the dielectric inclusion (barium titanate, BT) is in PC.
The MWNTs were modified using polyaniline, which facilitates better charge
transport in the blends. Furthermore, by introducing surface active groups on BT
nanoparticles and changing the macroscopic processing conditions, the
localization of BT nanoparticles can be tailored, otherwise BT nanoparticles
would localize in the preferred phase (PVDF). In this study, we have shown that
by ordered arrangement of nanoparticles, the incoming EM radiation can be
attenuated. For instance, when PANI-MWNTs were localized in PVDF, the shielding
was mainly through reflection. Now by localizing the conducting inclusion and the
magnetic lossy materials in PVDF and the dielectric materials in PC, an
outstanding shielding effectiveness of ca. -37 dB was achieved where shielding
was mainly through absorption (ca. 90%). Thus, this study clearly demonstrates
that lightweight microwave absorbers can be designed using polymer blends as a
tool.
PMID- 26431366
TI - Global Burden of Leptospirosis: Estimated in Terms of Disability Adjusted Life
Years.
AB - BACKGROUND: Leptospirosis, a spirochaetal zoonosis, occurs in diverse
epidemiological settings and affects vulnerable populations, such as rural
subsistence farmers and urban slum dwellers. Although leptospirosis can cause
life-threatening disease, there is no global burden of disease estimate in terms
of Disability Adjusted Life Years (DALYs) available. METHODOLOGY/PRINCIPAL
FINDINGS: We utilised the results of a parallel publication that reported global
estimates of morbidity and mortality due to leptospirosis. We estimated Years of
Life Lost (YLLs) from age and gender stratified mortality rates. Years of Life
with Disability (YLDs) were developed from a simple disease model indicating
likely sequelae. DALYs were estimated from the sum of YLLs and YLDs. The study
suggested that globally approximately 2.90 million DALYs are lost per annum (UIs
1.25-4.54 million) from the approximately annual 1.03 million cases reported
previously. Males are predominantly affected with an estimated 2.33 million DALYs
(UIs 0.98-3.69) or approximately 80% of the total burden. For comparison, this is
over 70% of the global burden of cholera estimated by GBD 2010. Tropical regions
of South and South-east Asia, Western Pacific, Central and South America, and
Africa had the highest estimated leptospirosis disease burden.
CONCLUSIONS/SIGNIFICANCE: Leptospirosis imparts a significant health burden
worldwide, which approach or exceed those encountered for a number of other
zoonotic and neglected tropical diseases. The study findings indicate that
highest burden estimates occur in resource-poor tropical countries, which include
regions of Africa where the burden of leptospirosis has been under-appreciated
and possibly misallocated to other febrile illnesses such as malaria.
PMID- 26431368
TI - SLC38A9: A lysosomal amino acid transporter at the core of the amino acid-sensing
machinery that controls MTORC1.
AB - The mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1)
acts as a crucial regulator of cellular metabolism by integrating growth factor
presence, energy and nutrient availability to coordinate anabolic and catabolic
processes, and controls cell growth and proliferation. Amino acids are critical
for MTORC1 activation, but the molecular mechanisms involved in sensing their
presence are just beginning to be understood. We recently reported that the
previously uncharacterized amino acid transporter SLC38A9 is a member of the
lysosomal sensing machinery that signals amino acid availability to MTORC1.
SLC38A9 is the first component of this complex shown to physically engage amino
acids, suggesting a role at the core of the amino acid-sensing mechanism.
PMID- 26431369
TI - Virulence of Bacteria Colonizing Vascular Bundles in Ischemic Lower Limbs.
AB - BACKGROUND: We documented previously the presence of bacterial flora in vascular
bundles, lymphatics, and lymph nodes of ischemic lower limbs amputated because of
multifocal atheromatic changes that made them unsuitable for reconstructive
surgery and discussed their potential role in tissue destruction. The question
arose why bacterial strains inhabiting lower limb skin and considered to be
saprophytes become pathogenic once they colonize deep tissues. Bacterial
pathogenicity is evoked by activation of multiple virulence factors encoded by
groups of genes. METHODS: We identified virulence genes in bacteria cultured from
deep tissue of ischemic legs of 50 patients using a polymerase chain reaction
technique. RESULTS: The staphylococcal virulence genes fnbA (fibronectin-binding
protein A), cna (collagen adhesin precursor), and ica (intercellular adhesion)
were present in bacteria isolated from both arteries and, to a lesser extent,
skin. The IS256 gene, whose product is responsible for biofilm formation, was
more frequent in bacteria retrieved from the arteries than skin bacteria. Among
the virulence genes of Staphylococcus epidermidis encoding autolysin atlE, icaAB
(intercellular adhesion), and biofilm insert IS256, only the latter was detected
in arterial specimens. Bacteria cultured from the lymphatics did not reveal
expression of eta and IS256 in arteries. The Enterococcus faecalis asa 373
(aggregation substance) and cylA (cytolysin activator) frequency was greater in
arteries than in skin bacteria, as were the E. faecium cyl A genes. All
Pseudomonas aeruginosa virulence genes were present in bacteria cultured from
both the skin and arteries. Staphylococci colonizing arterial bundles and
transported to tissues via ischemic limb lymphatics expressed virulence genes at
greater frequency than did those dwelling on the skin surface. Moreover,
enterococci and Pseudomonas isolated from arterial bundles expressed many
virulence genes. CONCLUSIONS: These findings may add to the understanding of the
mechanism of development of destructive changes in lower limb ischemic tissues by
the patient's, but not hospital-acquired, bacteria, as well as the generally
unsatisfactory results of antibiotic administration in these cases. More
aggressive antibiotic therapy targeted at the virulent species should be applied.
PMID- 26431370
TI - Tailoring the Pore Size and Functionality of UiO-Type Metal-Organic Frameworks
for Optimal Nerve Agent Destruction.
AB - Evaluation of UiO-66 and UiO-67 metal-organic framework derivatives as catalysts
for the degradation of soman, a chemical warfare agent, showed the importance of
both the linker size and functionality. The best catalysts yielded half-lives of
less than 1 min. Further testing with a nerve agent simulant established that
different rate-assessment techniques yield similar values for degradation half
lives.
PMID- 26431371
TI - Risk factors for mortality in patients with Staphylococcus aureus bloodstream
infection.
AB - In this two year retrospective analysis, we evaluated the epidemiology and risk
factors for mortality of Staphylococcus aureus bloodstream infection (SaBSI).
Methicillin-susceptible S. aureus (MSSA) was isolated in 84 (44.2%) and
methicillin-resistant S. aureus (MRSA) in 106 episodes (55.8%). The mortality
rate after 21 days was 16.4%. At univariate analysis older age, no removal of
central venous catheter (CVC), prosthetic heart valves, severe sepsis, septic
shock and high APACHE II score were significantly associated with mortality,
whereas treatment duration > 48 hours, appropriate targeted therapy and prolonged
treatment duration were significantly associated with survival. At multivariate
analysis, prosthetic valves, septic shock and fever 48 hours after the diagnosis
were significantly related to mortality. In this study, the mortality was
associated with clinical rather than microbiological factors.
PMID- 26431372
TI - Comorbidity in Migraine with Functional Somatic Syndromes, Psychiatric Disorders
and Inflammatory Diseases: A Matter of Central Sensitization?
AB - To approach the questions as to why migraine appears to be associated with
functional somatic syndromes (FSSs) and whether central sensitization may be an
underlying mechanism, the present study investigated (a) comorbidity with
diagnoses of three FSSs, three psychiatric disorders, and three inflammatory
diseases, (b) degree of mental health problems (stress, burnout, anxiety,
depression and somatization), and (c) prevalence of ten cognitive/affective and
nine airway symptoms in persons with migraine in the general population. From a
randomized and stratified Swedish adult sample, questionnaire data were analyzed
from 151 individuals with a diagnosis of migraine and 3,255 without migraine. The
results showed (a) significant comorbidity in migraine with all FSSs, psychiatric
disorders and inflammatory diseases, (b) significantly elevated scores on stress,
burnout, anxiety, depression, and somatization, and (c) relatively high
prevalence rates on almost all symptoms. Taken together, the results motivate
future study of central sensitization as a mechanism underlying migraine.
PMID- 26431373
TI - Effect of antiretroviral therapy on hemoglobin A2 values can have implications in
antenatal beta-thalassemia screening programs.
AB - BACKGROUND: Raised hemoglobin-A2 (HbA2) is the diagnostic hallmark of beta
thalassemia trait (betaTT). Diagnostic difficulties may arise in HIV-positive
patients on antiretroviral therapy (ART). We compared the effect of various
antiretroviral drugs on HbA2 levels. We attempted to determine which drugs
elevate HbA2 levels causing a false-positive diagnosis of betaTT and correlate
the findings with red cell indices. METHODS: A retrospective analysis of the
records of an antenatal thalassemia screening program was carried out for 78 HIV
positive adults (70 antenatal women and 8 husbands) to study the effect of
antiretroviral drugs on HbA2 levels. Three had betaTT; 20 treatment-naive
subjects constituted controls. The effects of zidovudine (36 cases), stavudine (7
cases), and tenofovir (12 cases) were evaluated. High-performance liquid
chromatography was done for HbA2 levels. Values of 3.5-3.9% were borderline and
>= 4% with hypochromic microcytosis was considered to be betaTT. RESULTS: Twenty
individuals not on ART had normal HbA2%. Three patients had betaTT and showed
hypochromic microcytosis despite being on zidovudine. Fourteen of 55 patients on
treatment (25.5%) had borderline HbA2 values (mean 3.7%): 11 were on a zidovudine
based regimen and 3 on a stavudine-based regimen. One patient on zidovudine had
4.1% HbA2 with normal Hb and severe macrocytosis (MCV 128.5 fl), leading to a
false suspicion of betaTT. All patients on tenofovir had normal HbA2.
Hematological parameters, including mean corpuscular volume (MCV), mean
corpuscular haemoglobin (MCH), and HbA2 levels were increased due to
antiretroviral drugs zidovudine and stavudine. CONCLUSION: Treatment-naive
subjects and those on tenofovir showed no effect on HbA2 levels compared with
zidovudine and stavudine. A proportion of patients on zidovudine or stavudine had
borderline elevated HbA2 levels, which could lead to a false impression of
betaTT.
PMID- 26431375
TI - Flirting with Danger: Power and Choice in Heterosexual Relationships, Produced,
directed, and edited by Sut Jhally and Andrew Killoy.
PMID- 26431374
TI - Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in
Asian Indians.
AB - BACKGROUND: Estradiol, testosterone (T), and sex hormone binding globulin (SHBG)
levels are associated with lipid subfractions in men and women. Our objective was
to determine if associations are independent from adipose tissue area among Asian
Indians. METHODS: We used data from 42 women and 57 Asian Indian men who did not
use exogenous steroids or lipid-lowering medications. Lipoprotein subfractions
including low-density lipoprotein cholesterol (LDL), very low-density lipoprotein
cholesterol (VLDL), and intermediate density lipoprotein (IDL) were assessed by
ion mobility spectrometry. Intra-abdominal adiposity was assessed by computed
tomography. Multivariable regression models estimated the association between sex
hormones with lipoprotein subfractions before and after adjustment for adiposity.
RESULTS: Among women, lower logSHBG levels were associated with smaller logLDL
particle size and higher logtriglycerides, logVLDL, and logIDL, although these
associations were attenuated with adjustment for visceral adiposity in
particular. Among women, lower logSHBG levels was significantly associated with
lower logmedium LDL and logsmall LDL concentrations even after consideration of
visceral and hepatic adiposity and insulin resistance as represented by the
homeostasis model assessment of insulin resistance (HOMA-IR). Among men, lower
logSHBG was also associated with smaller logLDL peak diameter size and higher
logtriglycerides and logVLDL, even after adjustment for HOMA-IR and adiposity.
Relationships between sex steroids and lipid subfractions were not significant
among women. Among men, higher total testosterone was associated with higher
logHDL and logLDL particle size, and lower logtriglycerides and logVLDL, but
these associations were partially attenuated with adjustment for adiposity and
HOMA-IR. CONCLUSIONS: Among Asian Indians, SHBG is associated with more favorable
lipid subfraction concentrations, independent of hepatic and visceral fat.
PMID- 26431376
TI - Vesicular stomatitis virus expressing interferon-beta is oncolytic and promotes
antitumor immune responses in a syngeneic murine model of non-small cell lung
cancer.
AB - Vesicular stomatitis virus (VSV) is a potent oncolytic virus for many tumors. VSV
that produces interferon-beta (VSV-IFNbeta) is now in early clinical testing for
solid tumors. Here, the preclinical activity of VSV and VSV-IFNbeta against non
small cell lung cancer (NSCLC) is reported. NSCLC cell lines were treated in
vitro with VSV expressing green fluorescence protein (VSV-GFP) and VSV-IFNbeta.
VSV-GFP and VSV-IFNbeta were active against NSCLC cells. JAK/STAT inhibition with
ruxolitinib re-sensitized resistant H838 cells to VSV-IFNbeta mediated oncolysis.
Intratumoral injections of VSV-GFP and VSV-IFNbeta reduced tumor growth and
weight in H2009 nude mouse xenografts (p < 0.01). A similar trend was observed in
A549 xenografts. Syngeneic LM2 lung tumors grown in flanks of A/J mice were
injected with VSV-IFNbeta intratumorally. Treatment of LM2 tumors with VSV
IFNbeta resulted in tumor regression, prolonged survival (p < 0.0001), and cure
of 30% of mice. Intratumoral injection of VSV-IFNbeta resulted in decreased tumor
infiltrating regulatory T cells (Treg) and increased CD8+ T cells. Tumor cell
expression of PDL-1 was increased after VSV-IFNbeta treatment. VSV-IFNbeta has
potent antitumor effects and promotes systemic antitumor immunity. These data
support further clinical investigation of VSV-IFNbeta for NSCLC.
PMID- 26431377
TI - Pharmacologic regulation of AMPK in breast cancer affects cytoskeletal properties
involved with microtentacle formation and re-attachment.
AB - The presence of tumor cells in the circulation is associated with a higher risk
of metastasis in patients with breast cancer. Circulating breast tumor cells use
tubulin-based structures known as microtentacles (McTNs) to re-attach to
endothelial cells and arrest in distant organs. McTN formation is dependent on
the opposing cytoskeletal forces of stable microtubules and the actin network.
AMP-activated protein kinase (AMPK) is a cellular metabolic regulator that can
alter actin and microtubule organization in epithelial cells. We report that AMPK
can regulate the cytoskeleton of breast cancer cells in both attached and
suspended conditions. We tested the effects of AMPK on microtubule stability and
the actin-severing protein, cofilin. AMPK inhibition with compound c increased
both microtubule stability and cofilin activation, which also resulted in higher
McTN formation and re-attachment. Conversely, AMPK activation with A-769662
decreased microtubule stability and cofilin activation with concurrent decreases
in McTN formation and cell re-attachment. This data shows for the first time that
AMPK shifts the balance of cytoskeletal forces in suspended breast cancer cells,
which affect their ability to form McTNs and re-attach. These results support a
model where AMPK activators may be used therapeutically to reduce the metastatic
efficiency of breast tumor cells.
PMID- 26431378
TI - Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial
dysfunction and displayed synergistic lethality with piperlongumine in gastric
cancer.
AB - Gastric cancer (GC) is one of the leading causes of cancer mortality in the
world. In addressing the need of treatments for relapsed disease, we report the
identification of an existing U.S. Food and Drug Administration-approved small
molecule drug to repurpose for GC treatment. Auranofin (AF), clinically used to
treat rheumatic arthritis, but it exhibited preclinical efficacy in GC cells. By
increasing intracellular reactive oxygen species (ROS) levels, AF induces a
lethal endoplasmic reticulum stress response and mitochondrial dysfunction in
cultured GC cells. Blockage of ROS production reversed AF-induced ER stress and
mitochondrial pathways activation as well as apoptosis. In addition, AF displays
synergistic lethality with an ROS-generating agent piperlongumine, which is a
natural product isolated from the long pepper Piper longum L. Taken together,
this work provides a novel anticancer candidate for the treatment of gastric
cancer. More importantly, it reveals that increased ROS generation might be an
effective strategy in treating human gastric cancer.
PMID- 26431379
TI - Metformin and temozolomide act synergistically to inhibit growth of glioma cells
and glioma stem cells in vitro and in vivo.
AB - Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults. In
spite of advances in diagnosis and therapy, the prognosis of patients with GBM
has remained dismal. The fast recurrence and multi-drug resistance are some of
the key challenges in combating brain tumors. Glioma stem cells (GSCs) which are
considered the source of relapse and chemoresistance, the need for more effective
therapeutic options is overwhelming. In our present work, we found that combined
treatment with temozolomide (TMZ) and metformin (MET) synergistically inhibited
proliferation and induced apoptosis in both glioma cells and GSCs. Combination of
TMZ and MET significantly reduced the secondary gliosphere formation and
expansion of GSCs. We first demonstrated that MET effectively inhibited the AKT
activation induced by TMZ, and a combination of both drugs led to enhanced
reduction of mTOR, 4EBP1 and S6K phosphorylation. In addition, the combination of
the two drugs was accompanied with a powerful AMP-activated protein kinase (AMPK)
activation, while this pathway is not determinant. Xenografts performed in nude
mice demonstrate in vivo demonstrated that combined treatment significantly
reduced tumor growth rates and prolonged median survival of tumor-bearing mice.
In conclusion, TMZ in combination with MET synergistically inhibits the GSCs
proliferation through downregulation of AKT-mTOR signaling pathway. The combined
treatment of two drugs inhibits GSCs self-renewal capability and partly
eliminates GSCs in vitro and in vivo. This combined treatment could be a
promising option for patients with advanced GBM.
PMID- 26431380
TI - Usp22 deficiency impairs intestinal epithelial lineage specification in vivo.
AB - Epigenetic regulatory mechanisms play a central role in controlling gene
expression during development, cell differentiation and tumorigenesis.
Monoubiquitination of histone H2B is one epigenetic modification which is
dynamically regulated by the opposing activities of specific ubiquitin ligases
and deubiquitinating enzymes (DUBs). The Ubiquitin-specific Protease 22 (USP22)
is the ubiquitin hydrolase component of the human SAGA complex which
deubiquitinates histone H2B during transcription. Recently, many studies have
investigated an oncogenic potential of USP22 overexpression. However, its
physiological function in organ maintenance, development and its cellular
function remain largely unknown. A previous study reported embryonic lethality in
Usp22 knockout mice. Here we describe a mouse model with a global reduction of
USP22 levels which expresses the LacZ gene under the control of the endogenous
Usp22 promoter. Using this reporter we found Usp22 to be ubiquitously expressed
in murine embryos. Notably, adult Usp2(2lacZ/lacZ) displayed low residual Usp22
expression levels coupled with a reduced body size and weight. Interestingly, the
reduction of Usp22 significantly influenced the frequency of differentiated cells
in the small intestine and the brain while H2B and H2Bub1 levels remained
constant. Taken together, we provide evidence for a physiological role for USP22
in controlling cell differentiation and lineage specification.
PMID- 26431381
TI - Inhibition of testicular embryonal carcinoma cell tumorigenicity by peroxisome
proliferator-activated receptor-beta/delta- and retinoic acid receptor-dependent
mechanisms.
AB - Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) has
important physiological functions in control of cell growth, lipid and glucose
homeostasis, differentiation and inflammation. To investigate the role of
PPARbeta/delta in cancer, stable human testicular embryonal carcinoma cell lines
were developed that constitutively express PPARbeta/delta. Expression of
PPARbeta/delta caused enhanced activation of the receptor, and this significantly
decreased proliferation, migration, invasion, anchorage-independent growth, and
also reduced tumor mass and volume of ectopic xenografts derived from NT2/D1
cells compared to controls. The changes observed in xenografts were associated
with decreased PPARbeta/delta-dependent expression of proliferating cell nuclear
antigen and octamer-binding transcription factor-3/4, suggesting suppressed tumor
proliferation and induction of differentiation. Inhibition of migration and
invasion was mediated by PPARbeta/delta competing with formation of the retinoic
acid receptor (RAR)/retinoid X receptor (RXR) complex, resulting in attenuation
of RARalpha-dependent matrix metalloproteinase-2 expression and activity. These
results demonstrate that PPARbeta/delta mediates attenuation of human testicular
embryonal carcinoma cell progression through a novel RAR-dependent mechanism and
suggest that activation of PPARbeta/delta inhibits RAR/RXR dimerization and
represents a new therapeutic strategy.
PMID- 26431383
TI - Predicted vitamin D status during pregnancy in relation to offspring forearm
fractures in childhood: a study from the Danish National Birth Cohort.
AB - In a prospective cohort study, the association between maternal vitamin D status
during pregnancy and offspring forearm fractures during childhood and adolescence
was analysed in 30 132 mother and child pairs recruited to the Danish National
Birth Cohort between 1996 and 2002. Data on characteristics, dietary factors and
lifestyle factors were collected on several occasions during pregnancy. We
analysed the association between predicted vitamin D status, based on a subsample
with 25-hydroxyvitamin D (25(OH)D) biomarker measurements (n 1497) from gestation
week 25, and first-time forearm fractures among offspring between birth and end
of follow-up. Diagnoses were extracted from the Danish National Patient Register.
Multivariable Cox regression models using age as the underlying time scale
indicated no overall association between predicted vitamin D status (based on
smoking, season, dietary and supplementary vitamin D intake, tanning bed use and
outdoor physical activity) in pregnancy and offspring forearm fractures.
Likewise, measured 25(OH)D, tanning bed use and dietary vitamin D intake were not
associated with offspring forearm fractures. In mid-pregnancy, 91 % of the women
reported intake of vitamin D from dietary supplements. Offspring of women who
took >10 ug/d in mid-pregnancy had a significantly increased risk for fractures
compared with the reference level of zero intake (hazard ratios (HR) 1.31; 95% CI
1.06, 1.62), but this was solely among girls (HR 1.48; 95% CI 1.10, 2.00).
Supplement use in the peri-conceptional period exhibited similar pattern,
although not statistically significant. In conclusion, our data indicated no
protective effect of maternal vitamin D status with respect to offspring forearm
fractures.
PMID- 26431382
TI - Cigarette side-stream smoke lung and bladder carcinogenesis: inducing mutagenic
acrolein-DNA adducts, inhibiting DNA repair and enhancing anchorage-independent
growth cell transformation.
AB - Second-hand smoke (SHS) is associated with 20-30% of cigarette-smoke related
diseases, including cancer. Majority of SHS (>80%) originates from side-stream
smoke (SSS). Compared to mainstream smoke, SSS contains more tumorigenic
polycyclic aromatic hydrocarbons and acrolein (Acr). We assessed SSS-induced
benzo(a)pyrene diol epoxide (BPDE)- and cyclic propano-deoxyguanosine (PdG)
adducts in bronchoalveolar lavage (BAL), lung, heart, liver, and bladder-mucosa
from mice exposed to SSS for 16 weeks. In SSS exposed mice, Acr-dG adducts were
the major type of PdG adducts formed in BAL (p < 0.001), lung (p < 0.05), and
bladder mucosa (p < 0.001), with no significant accumulation of Acr-dG adducts in
heart or liver. SSS exposure did not enhance BPDE-DNA adduct formation in any of
these tissues. SSS exposure reduced nucleotide excision repair (p < 0.01) and
base excision repair (p < 0.001) in lung tissue. The levels of DNA repair
proteins, XPC and hOGG1, in lung tissues of exposed mice were significantly (p <
0.001 and p < 0.05) lower than the levels in lung tissues of control mice. We
found that Acr can transform human bronchial epithelial and urothelial cells in
vitro. We propose that induction of mutagenic Acr-DNA adducts, inhibition of DNA
repair, and induction of cell transformation are three mechanisms by which SHS
induces lung and bladder cancers.
PMID- 26431390
TI - Using Virtual Technology to Promote Functional Communication in Aphasia:
Preliminary Evidence From Interactive Dialogues With Human and Virtual
Clinicians.
AB - PURPOSE: We investigated the feasibility of using a virtual clinician (VC) to
promote functional communication abilities of persons with aphasia (PWAs). We
aimed to determine whether the quantity and quality of verbal output in dialogues
with a VC would be the same or greater than those with a human clinician (HC).
METHOD: Four PWAs practiced dialogues for 2 sessions each with a HC and VC.
Dialogues from before and after practice were transcribed and analyzed for
content. We compared measures taken before and after practice in the VC and HC
conditions. RESULTS: Results were mixed. Participants either produced more verbal
output with the VC or showed no difference on this measure between the VC and HC
conditions. Participants also showed some improvement in postpractice narratives.
CONCLUSION: Results provide support for the feasibility and applicability of
virtual technology to real-life communication contexts to improve functional
communication in PWAs.
PMID- 26431391
TI - Problems and Pitfalls in the Analysis of Amygdalin and Its Epimer.
AB - alpha-[(6-O-beta-d-Glucopyranosyl-beta-d-glucopyranosyl)oxy]-(alphaR)
benzeneacetonitrile, or R-amygdalin, is the most common cyanogenic glycoside
found in seeds and kernels of the Rosaceae family and other plant genera such as
Passiflora. Many commercially important seeds are analyzed for amygdalin content.
In "alternative medicine", amygdalin has been sold as a treatment for cancer for
several decades without any rigorous scientific support for its efficacy. We have
found that there are some inconsistencies and possible problems in the published
analytical chemistry of amygdalin. It is shown that some analytical approaches do
not account for the presence of the S-isomer; therefore, a fast reliable method
was developed using a chiral stationary phase and HPLC. This approach allows
"real-time" monitoring and complete and highly efficient separations. It is found
that the S-amygdalin continuously forms in aqueous solutions. A striking result
is that the conversion of amygdalin is glassware dependent. "Clean" vials from
various vendors can show drastically different reaction rates of the conversion
to the isomer (S-amygdalin, also called neo-amygdalin). The epimerization
kinetics are dependent on the solvent, temperature, pH, and the nature of the
container. For example, epimerization in water was complete in <15 min in a new
glass vial taken from the box, whereas it can take >1 h in specially cleaned
glassware. Conversely, epimerization can be significantly delayed at high
temperature if high-density polyethylene is used as the container. Hence, inert
plastic containers are recommended for storage of aqueous amygdalin solutions.
Commercial preparations of R-amygdalin actually contain greater quantities of S
amygdalin and ~ 5% of other degradation products.
PMID- 26431392
TI - Highly Efficient Copper-Indium-Selenide Quantum Dot Solar Cells: Suppression of
Carrier Recombination by Controlled ZnS Overlayers.
AB - Copper-indium-selenide (CISe) quantum dots (QDs) are a promising alternative to
the toxic cadmium- and lead-chalcogenide QDs generally used in photovoltaics due
to their low toxicity, narrow band gap, and high absorption coefficient. Here, we
demonstrate that the photovoltaic performance of CISe QD-sensitized solar cells
(QDSCs) can be greatly enhanced simply by optimizing the thickness of ZnS
overlayers on the QD-sensitized TiO2 electrodes. By roughly doubling the
thickness of the overlayers compared to the conventional one, conversion
efficiency is enhanced by about 40%. Impedance studies reveal that the thick ZnS
overlayers do not affect the energetic characteristics of the photoanode, yet
enhance the kinetic characteristics, leading to more efficient photovoltaic
performance. In particular, both interfacial electron recombination with the
electrolyte and nonradiative recombination associated with QDs are significantly
reduced. As a result, our best cell yields a conversion efficiency of 8.10% under
standard solar illumination, a record high for heavy metal-free QD solar cells to
date.
PMID- 26431393
TI - Synthesis and Properties of the 5-Methyluridine Derivative of 3,4-Dihydro-2H
pyran-Bridged Nucleic Acid (DpNA).
AB - A novel 2'-O,4'-C-bridged nucleic acid, 3,4-dihydro-2H-pyran bridge moiety
(DpNA), with a dioxabicyclo[3.2.1]oct-3-ene ring was designed. Construction of
the dihydropyran bridge was achieved by dehydration of a six-membered hemiacetal
ring, and the DpNA monomer was synthesized in 10 steps from 5-methyluridine
(total yield 9%). The synthesized DpNA monomer was incorporated into
oligonucleotides to examine the properties of the modified oligonucleotides. The
DpNA-modified oligonucleotides possessed high affinity toward ssRNA and were more
resistant to nucleases compared to the corresponding natural oligonucleotide.
PMID- 26431394
TI - Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing
Activities.
AB - Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5
octadienyl]chalcone (1), (+/-)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy
3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3
dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone
(4), and (+/-)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone
(5), were isolated from the aerial parts of Angelica keiskei Koidzumi together
with eight known chalcones, 6-13, which were identified as (+/-)-4,2',4'
trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6),
xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin
(10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13),
respectively. Chalcones 1-13 were evaluated for their promoter activity on heat
shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated
the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 MUM,
respectively. Further protein expression patterns of heat shock factor 1 (HSF1),
HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of
HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control,
respectively, without any significant cellular cytotoxicities, whereas 1 did not
induce any expression of these proteins. As a result, 6 seems to be a prospective
HSP inducer.
PMID- 26431395
TI - Exome Capture with Heterologous Enrichment in Pig (Sus scrofa).
AB - The discovery of new protein-coding DNA variants related to carcass traits is
very important for the Italian pig industry, which requires heavy pigs with
higher thickness of subcutaneous fat for Protected Designation of Origin (PDO)
productions. Exome capture techniques offer the opportunity to focus on the
regions of DNA potentially related to the gene and protein expression. In this
research a human commercial target enrichment kit was used to evaluate its
performances for pig exome capture and for the identification of DNA variants
suitable for comparative analysis. Two pools of 30 pigs each, crosses of Italian
Duroc X Large White (DU) and Commercial hybrid X Large White (HY), were used and
NGS libraries were prepared with the SureSelectXT Target Enrichment System for
Illumina Paired-End Sequencing Library (Agilent). A total of 140.2 M and 162.5 M
of raw reads were generated for DU and HY, respectively. Average coverage of all
the exonic regions for Sus scrofa (ENSEMBL Sus_scrofa.Sscrofa10.2.73.gtf) was
89.33X for DU and 97.56X for HY; and 35% of aligned bases uniquely mapped to off
target regions. Comparison of sequencing data with the Sscrofa10.2 reference
genome, after applying hard filtering criteria, revealed a total of 232,530
single nucleotide variants (SNVs) of which 20.6% mapped in exonic regions and
49.5% within intronic regions. The comparison of allele frequencies of 213
randomly selected SNVs from exome sequencing and the same SNVs analyzed with a
Sequenom MassARRAY(r) system confirms that this "human-on-pig" approach offers
new potentiality for the identification of DNA variants in protein-coding genes.
PMID- 26431396
TI - Bilateral Pneumothoraces Following BiV ICD Placement: A Case of Buffalo Chest
Syndrome.
AB - BACKGROUND: Contralateral pneumothorax following device implantation on the left
side has been reported in a few cases. The majority of contralateral
pneumothoraces showed evidence of atrial perforation on computed tomography (CT),
echocardiography, or chest x-rays and required lead revision. To the best of our
knowledge there is only 1 other reported case of contralateral pneumothorax
without evidence of macro-displacement of the atrial lead. In that case the
patient experienced a right-sided pneumothorax on day 1 after undergoing
repositioning of the atrial lead. CASE REPORT: The current case is unique on
several accounts, including timing of the contralateral pneumothorax and no
evidence of associated atrial lead perforation on device interrogation or CT
imaging. Furthermore, the appearance of contralateral pneumothorax within 8 hours
of clamping of the ipsilateral chest tube argues in favor of a pleuro-pleural
fistula. CONCLUSIONS: The term 'buffalo chest' refers to a single pleural space,
with no anatomical separation of the 2 hemithoraces, as seen in an American
buffalo or bison. We believe this to be a case of buffalo chest syndrome.
PMID- 26431397
TI - Etiology of Non-Cystic Fibrosis Bronchiectasis in Adults and Its Correlation to
Disease Severity.
AB - RATIONALE: Testing for underlying etiology is a key part of bronchiectasis
management, but it is unclear whether the same extent of testing is required
across the spectrum of disease severity. OBJECTIVES: The aim of the present study
was to identify the etiology of bronchiectasis across European cohorts and
according to different levels of disease severity. METHODS: We conducted an
analysis of seven databases of adult outpatients with bronchiectasis
prospectively enrolled at the bronchiectasis clinics of university teaching
hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium;
Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every
site underwent the same comprehensive diagnostic workup as suggested by the
British Thoracic Society. MEASUREMENTS AND MAIN RESULTS: Among the 1,258 patients
enrolled, an etiology of bronchiectasis was determined in 60%, including
postinfective (20%), chronic obstructive pulmonary disease related (15%),
connective tissue disease related (10%), immunodeficiency related (5.8%), and
asthma related (3.3%). An etiology leading to a change in patient's management
was identified in 13% of the cases. No significant differences in the etiology of
bronchiectasis were present across different levels of disease severity, with the
exception of a higher prevalence of chronic obstructive pulmonary disease-related
bronchiectasis (P < 0.001) and a lower prevalence of idiopathic bronchiectasis (P
= 0.029) in patients with severe disease. CONCLUSIONS: Physicians should not be
guided by disease severity in suspecting specific etiologies in patients with
bronchiectasis, although idiopathic bronchiectasis appears to be less common in
patients with the most severe disease.
PMID- 26431398
TI - Biofilm Formation Mechanisms of Pseudomonas aeruginosa Predicted via Genome-Scale
Kinetic Models of Bacterial Metabolism.
AB - A hallmark of Pseudomonas aeruginosa is its ability to establish biofilm-based
infections that are difficult to eradicate. Biofilms are less susceptible to host
inflammatory and immune responses and have higher antibiotic tolerance than free
living planktonic cells. Developing treatments against biofilms requires an
understanding of bacterial biofilm-specific physiological traits. Research
efforts have started to elucidate the intricate mechanisms underlying biofilm
development. However, many aspects of these mechanisms are still poorly
understood. Here, we addressed questions regarding biofilm metabolism using a
genome-scale kinetic model of the P. aeruginosa metabolic network and gene
expression profiles. Specifically, we computed metabolite concentration
differences between known mutants with altered biofilm formation and the wild
type strain to predict drug targets against P. aeruginosa biofilms. We also
simulated the altered metabolism driven by gene expression changes between
biofilm and stationary growth-phase planktonic cultures. Our analysis suggests
that the synthesis of important biofilm-related molecules, such as the quorum
sensing molecule Pseudomonas quinolone signal and the exopolysaccharide Psl, is
regulated not only through the expression of genes in their own synthesis
pathway, but also through the biofilm-specific expression of genes in pathways
competing for precursors to these molecules. Finally, we investigated why mutants
defective in anthranilate degradation have an impaired ability to form biofilms.
Alternative to a previous hypothesis that this biofilm reduction is caused by a
decrease in energy production, we proposed that the dysregulation of the
synthesis of secondary metabolites derived from anthranilate and chorismate is
what impaired the biofilms of these mutants. Notably, these insights generated
through our kinetic model-based approach are not accessible from previous
constraint-based model analyses of P. aeruginosa biofilm metabolism. Our
simulation results showed that plausible, non-intuitive explanations of difficult
to-interpret experimental observations could be generated by integrating genome
scale kinetic models with gene expression profiles.
PMID- 26431399
TI - Ovarian Transcriptome Analysis of Portunus trituberculatus Provides Insights into
Genes Expressed during Phase III and IV Development.
AB - Enhancing the production of aquatic animals is crucial for fishery management and
aquaculture applications. Ovaries are specialized tissues that play critical
roles in producing oocytes and hormones. Significant biochemical changes take
place during the sexual maturation of Portunus trituberculatus, but the genetics
of this process has not been extensively studied. Transcriptome sequencing can be
used to determine gene expression changes within specific periods. In the current
study, we used transcriptome sequencing to produce a comprehensive transcript
dataset for the ovarian development of P. trituberculatus. Approximately 100
million sequencing reads were generated, and 126,075 transcripts were assembled.
Functional annotation of the obtained transcripts revealed important pathways in
ovarian development, such as those involving the vitellogenin gene. Also, we
performed deep sequencing of ovaries in phases III and IV of sexual maturation in
P. trituberculatus. Differential analysis of gene expression identified 506
significantly differentially expressed genes, which belong to 20 pathway,
transporters, development, transcription factors, metabolism of other amino
acids, carbohydrate and lipid, solute carrier family members, and enzymes. Taken
together, our study provides the first comprehensive transcriptomic resource for
P. trituberculatus ovaries, which will strengthen understanding of the molecular
mechanisms underlying the sexual maturation process and advance molecular
nutritional studies of P. trituberculatus.
PMID- 26431401
TI - Correction: Phosphatidylcholine Supply to Peroxisomes of the Yeast Saccharomyces
cerevisiae.
PMID- 26431400
TI - 'Only Fathers Smoking' Contributes the Most to Socioeconomic Inequalities:
Changes in Socioeconomic Inequalities in Infants' Exposure to Second Hand Smoke
over Time in Japan.
AB - BACKGROUND: Exposure to second hand smoke (SHS) is one of the major causes of
premature death and disease among children. While socioeconomic inequalities
exist for adult smoking, such evidence is limited for SHS exposure in children.
Thus, this study examined changes over time in socioeconomic inequalities in
infants' SHS exposure in Japan. METHODS: This is a repeated cross-sectional study
of 41,833 infants born in 2001 and 32,120 infants born in 2010 in Japan from
nationally representative surveys using questionnaires. The prevalence of
infants' SHS exposure was determined and related to household income and parental
education level. The magnitudes of income and educational inequalities in
infants' SHS exposure were estimated in 2001 and 2010 using both absolute and
relative inequality indices. RESULTS: The prevalence of SHS exposure in infants
declined from 2001 to 2010. The relative index of inequality increased from 0.85
(95% confidence interval [CI], 0.80 to 0.89) to 1.47 (95% CI, 1.37 to 1.56) based
on income and from 1.22 (95% CI, 1.17 to 1.26) to 2.09 (95% CI, 2.00 to 2.17)
based on education. In contrast, the slope index of inequality decreased from
30.9 (95% CI, 29.3 to 32.6) to 20.1 (95% CI, 18.7 to 21.5) based on income and
from 44.6 (95% CI, 43.1 to 46.2) to 28.7 (95% CI, 27.3 to 30.0) based on
education. Having only a father who smoked indoors was a major contributor to
absolute income inequality in infants' SHS exposure in 2010, which increased in
importance from 45.1% in 2001 to 67.0% in 2010. CONCLUSIONS: The socioeconomic
inequalities in infants' second hand smoke exposure increased in relative terms
but decreased in absolute terms from 2001 to 2010. Further efforts are needed to
encourage parents to quit smoking and protect infants from second hand smoke
exposure, especially in low socioeconomic households that include non-smoking
mothers.
PMID- 26431403
TI - Highlights in GEP-NETs From the 2015 American Society of Clinical Oncology Annual
Meeting.
PMID- 26431402
TI - Factors Associated to Prevalence and Incidence of Carbapenem-Resistant
Enterobacteriaceae Fecal Carriage: A Cohort Study in a Mexican Tertiary Care
Hospital.
AB - BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) infections have emerged
as a serious threat to health worldwide. They are associated with increased
morbidity and mortality and are capable of silently colonizing the
gastrointestinal tract. Because of this, there is great interest to characterize
the epidemiology of CRE carriage and acquisition in healthcare facilities. The
aim of this study was to determine the prevalence and factors associated with CRE
fecal carriage (CRE-fc), and risk factors for incident cases. METHODS/RESULTS: A
cohort study was conducted at a tertiary care hospital from January 1st to April
30th, 2014 during a CRE outbreak. Weekly rectal swabs were performed in patients
considered at risk until discharge. CRE-fc prevalence was 10.9% (CI 95% 7.7-14.7)
among 330 patients. Treatment with carbapenems (OR 2.54, CI 95% 1.15-5.62);
transfer from an institution (OR 2.16, CI 95% 1.02-4.59); multi-drug resistant
infection within the previous six months (OR 2.81, CI 95% 1.47-5.36); intensive
care unit admission (OR 0.42, CI 95% 0.20-0.88); hematologic malignancy (OR 4.02,
CI 95% 1.88-8.06); invasive procedures (OR 2.18, CI 95% 1.10-4.32); and sharing a
room with a known CRE carrier (OR 3.0, CI 95% 1.43-6.31) were independently
associated factors for CRE-fc. Risk factors associated with CRE-fc incidence were
determined for 87 patients initially negative and with subsequent screening; the
incidence rate was 2.5 cases, per 1000 person-years (CI 95% 1.5-3.9).
Independently associated risk factors were carbapenem treatment (HR 2.68, CI 95%
1.03-6.98), hematologic malignancy (HR 5.74, 95% CI 2.46-13.4) and a mean daily
colonization pressure >=10% (HR 5.03, IC 95% 1.77-14.28). OXA-48-like (OXA-232)
and CTX-M-15 were the predominantly identified mechanisms of resistance.
CONCLUSIONS: We found an elevated incidence and prevalence of CRE-fc in our
hospital. Hematologic patients need to be considered a population at risk, and
antibiotic stewardship along with infection control programs need to be improved
to avoid nosocomial spread.
PMID- 26431410
TI - Academic-Industry Partnerships in Alcohol and Gambling: a Continuum of Benefits
and Harms.
AB - There are many reasons why collaboration between academic institutions and
private industry should be encouraged. At the same time, such collaborations
raise the potential for profound conflicts of interest. Furthermore, there may be
different kinds of issues in different kinds of industry, as is reflected in the
metaphors we employ to think about them. The pharmaceutical industry is at times
viewed as a "good" industry that can go wrong, while the tobacco industry is
analogously viewed as a "bad" industry that can do little right. The alcohol and
gambling industries may be particularly useful to think through insofar as they
arguably require a continuum of benefits and harms to be acknowledged. I consider
a number of initiatives by the alcohol and gambling industry in South Africa, and
argue that there are real opportunities for delineating and developing more
robust models of academic-industry collaboration, which ensure that public health
is maximized in that country and elsewhere.
PMID- 26431409
TI - Overcoming Stagnation in the Levels and Distribution of Child Mortality: The Case
of the Philippines.
AB - BACKGROUND: Health-related within-country inequalities continue to be a matter of
great interest and concern to both policy makers and researchers. This study aims
to assess the level and the distribution of child mortality outcomes in the
Philippines across geographical and socioeconomic indicators. METHODOLOGY: Data
on 159,130 children ever borne were analysed from five waves of the Philippine
Demographic and Health Survey. Direct estimation was used to construct under-five
and neonatal mortality rates for the period 1980-2013. Rate differences and
ratios, and where possible, slope and relative indices of inequality were
calculated to measure disparities on absolute and relative scales. Stratification
was undertaken by levels of rural/urban location, island groups and household
wealth. FINDINGS: National under-five and neonatal mortality rates have shown
considerable albeit differential reductions since 1980. Recently released data
suggests that neonatal mortality has declined following a period of stagnation.
Declines in under-five mortality have been accompanied by decreases in wealth and
geography-related absolute inequalities. However, relative inequalities for the
same markers have remained stable over time. For neonates, mixed evidence
suggests that absolute and relative inequalities have remained stable or may have
risen. CONCLUSION: In addition to continued reductions in under-five mortality,
new data suggests that the Philippines have achieved success in addressing the
commonly observed stagnated trend in neonatal mortality. This success has been
driven by economic improvement since 2006 as well as efforts to implement a
nationwide universal health care campaign. Yet, such patterns, nonetheless,
accorded with persistent inequalities, particularly on a relative scale. A
continued focus on addressing universal coverage, the influence of
decentralisation and armed conflict, and issues along the continuum of care is
advocated.
PMID- 26431411
TI - Differential Associations Between Depression, Risk Factors for Insulin Resistance
and Diabetes Incidence in a Large U.S. Sample.
AB - BACKGROUND: Depression frequently co-occurs with diabetes. The associations
between risk factors for insulin resistance and depression and diabetes can help
determine the relative importance of factors that contribute toward the
comorbidity. METHOD: Analyses of the NHANES I (n = 10,025) to examine the cross
sectional relationships between depression and risk factors for insulin
resistance at baseline using logistic regression and to explore the longitudinal
relationships between risk factors for insulin resistance and diabetes incidence
using Cox proportional hazards modeling. RESULTS: Many risk factors for insulin
resistance were associated with depression and diabetes incidence. Depression was
cross-sectionally associated with diabetes, but did not increase the risk for
diabetes incidence.These counterintuitive results can be explained primarily by
the differing relationships between risk factors for insulin resistance,
depression, and diabetes. LIMITATIONS: Lack of repeated measures of depression.
CONCLUSIONS: Lack of physical activity, hypertension, and inadequate sleep were
the risk factors for insulin resistance with the highest associations with both
depression and diabetes incidence.
PMID- 26431412
TI - Psychopathology and its Early Impact on Parenting Behaviors in Mothers: The
Interface between Adult and Infant Psychiatry.
AB - Parenting is, in its essence, the domain where adult mental health and infant's
mental and physical health meet in a complex and dynamic interplay. Becoming a
parent is a developmental challenge in itself, and often exacerbates an existing
mental illness, and in turn, maladaptive parenting impinges on the early parent
infant relationship, and on the infant's socio-emotional development and later
functioning. The capacity for mentalization is brought as a bridging concept
between adult and infant psychiatry. A few clinical vignettes illustrate the
dynamic interplay between very young children's vulnerabilities and needs and
their parents' strengths and weaknesses, leading to a complex interaction and
often to symptoms in both child and parent. In the light of the compelling data
about the impact of parental psychopathology on parenting behaviors and children
outcomes, there is an imperative need for a working alliance and on-going
communication between child and adult psychiatrists.
PMID- 26431413
TI - The Outcome of Severe Internalizing and Disruptive Disorders from Preschool into
Adolescence:A Follow-up Study.
AB - PURPOSE: In this study we aimed to examine the outcome of children's severe
psychiatric disorders from preschool into later childhood and adolescence.
METHOD: Forty preschool children (28 boys and 12 girls) treated in a tertiary
referral mental health center, evaluated at admission and 5.5 +/- 1.2 years
thereafter. RESULTS: Seven (58.3%) children diagnosed with internalizing
disorders at baseline were free of any psychiatric diagnosis at follow-up
(p=0.02). Conversely, only one child (8.3%) diagnosed with comorbid disruptive
internalizing disorders at baseline was free of any psychiatric disorder at
follow-up (p=1.0). Seven (43.7%) children diagnosed with disruptive disorders at
baseline were free of psychiatric diagnoses at follow-up (p=0.02). LIMITATIONS:
The small sample size and naturalistic nature of the study. CONCLUSION: The
trajectories of severe psychiatric disorders at preschool years are similar to
those reported in community samples and differ according to the baseline
diagnosis. Children with internalizing disorders show a much better recovery rate
than those with comorbid disruptive and internalizing disorders.
PMID- 26431414
TI - Feasibility of a Dual Evaluation/Intervention Program for Morbidly Obese
Adolescents.
AB - BACKGROUND: In the absence of evidence-based guidelines for screening adolescent
candidates for bariatric surgery, or improving their adherence to preoperative
recommendations, we designed a dual-phase multidisciplinary program aiming for
observation-based preoperative assessment/ intervention, as well as for post
operative/ conservative follow up. METHODS: This study focused on the
preoperative 3-month phase. Fifteen morbidly obese adolescents attending the
eating disorders unit of a pediatric hospital underwent the program protocol
consisting of medical examinations/ tests, psychological measures, self
monitoring, tailored diet, physical activity schedule, individual and group
cognitive behavior-oriented therapy, and psycho educational parent training.
RESULTS: All patients completed the preoperative phase. Most of them (70%)
followed the structured diet with a significant reduction in BMI. The patients
complied with self-monitoring, and body dissatisfaction score improved. Parental
participation in therapy was poor. Four patients with low adherence were found
ineligible for surgery. CONCLUSIONS: The findings support the feasibility of our
dual screening/intervention protocol. Measures to improve parental participation
are warranted.
PMID- 26431415
TI - Dental Health and the Type of Antipsychotic Treatment in Inpatients with
Schizophrenia.
AB - AIM: This study examined the association between dental conditions in
hospitalized patients with ICD-10 schizophrenia and type of antipsychotic
treatment. Based on the literature suggesting that atypical antipsychotics are
thought to be more tolerable than typical antipsychotics, we hypothesized that
hospitalized patients with schizophrenia treated with atypicals would have better
dental health than those treated with typicals alone or with a combination of
both (combined group). METHODS: A representative sample of 348 patients (69%
males), aged 51.4 (SD=14.5, range 31-58) years, was assessed on the standardized
criteria of the Decayed, Missing and Filled Teeth (DMFT) index and component
scores. Data on medication were extracted from patients' electronic medical
records. RESULTS: Patients treated with typicals had significantly higher DMFT
index scores than those who received atypicals (23.5+/-9.9 vs. 19.0+/-10.5; p <
0.05), and higher Missing (20.2+/-11.6 vs. 13.5+/-11.2; p < 0.01) and lower
Filled (1.0+/-2.4 vs. 2.1+/-3.9; p < 0.05) teeth component scores. No between
group differences in Decayed component scores were found (2.3+/-3.4 and 3.4+/
5.0, respectively; p > 0.05). The combined treatment group was situated in
between the typicals and atypicals groups on all measures. CONCLUSIONS: The
results suggest that patients with schizophrenia maintained on atypicals have
better dental health than patients treated with typicals or with a combination of
both. From an oral health perspective, monotherapy with atypicals is superior to
both typical and atypical/typical treatments. Although the choice between typical
and atypical antipsychotic agents is based mainly on clinical psychiatric
efficacy, the benefit of atypicals with regard to dental health should be taken
into consideration in clinician's decision making.
PMID- 26431416
TI - Severity of Psychiatric Disorders and Dental Health Among Psychiatric Outpatients
in Jerusalem, Israel.
AB - The association between severity of psychiatric disorder and dental disease has
not been adequately studied. The aim of the present study was to examine the
level of dental caries morbidity and the association with Severe Mental Illness
(SMI) and mild/moderate psychiatric disorders. The population sample included
patients aged 30 to 50, treated at the Hadassah psychiatric outpatient clinic,
after giving written informed consent. Exclusion criteria included eating
disorders which are recognized as being associated with several dental
pathologies. The term SMI, frequently used in the literature (1), refers to
psychiatric patients suffering from a significant mental disorder and implies a
greater burden of illness and dysfunction. The SMI group in this study included
patients suffering from schizophrenia, bipolar disorder, resistant depression and
chronic post-traumatic stress disorder (PTSD). The mild/ moderate illness group
consisted of all other psychiatric disorders on Axis I or II according to DSM IV
TR (2).
PMID- 26431417
TI - Validation of the HCR-20 Scale for Assessing Risk of Violent Behavior in Israeli
Psychiatric Inpatients.
AB - BACKGROUND: Assessment of risk of violent behavior in forensic psychiatric
practice is a complex and responsible clinical task and the use of a valid
instrument can make the expert's work more effective. The Historical Clinical and
Risk Management scale 20 (HCR-20) is a widely accepted measure of the risk of
violence, sexual and criminal behavior. The aim of this study was to validate the
HCR-20 in Israeli psychiatric inpatient settings. METHOD: In a prospective
design, data were collected on 150 male patients aged 15-65, diagnosed with ICD
10 schizophrenia, who were hospitalized in three wards: an acute psychiatric ward
(n=50), a high security ward (n=50), and an open ward (n=50). The HCR-20, as the
predictor measure, and the Positive and Negative Syndrome Scale, as a concurrent
measure, werecompleted at baseline, and the Violence Assessment Scale, as the
outcome measure, was completed at 6-, 12- and 18-month follow-up points. RESULTS:
Internal consistency reliability was good for the total HCR-20 scale,
satisfactory for the H-subscale, but low for the C- and R-subscales. Concurrent
validity was good for the C-subscale, and discriminative validity was reasonable
for the C- and H-subscales. The total scale as well as the Historical and
Clinical subscales predicted the risk of physical as well as physical/sexual
violent behavior at both 6- and 18-month follow-up points. CONCLUSIONS:
Appropriate psychometric properties of the HCR-20 suggest that it can serve as a
useful measure of the risk of violent behavior in psychiatric settings in Israel.
Further research is necessary to confirm norms and cut-off scores, using a larger
representative sample.
PMID- 26431418
TI - Negative and Positive Automatic thoughts in Social Anxiety Disorder.
AB - BACKGROUND: Social Anxiety Disorder (SAD) is characterized by fear and avoidance
in social situations where one is exposed to scrutiny by others. It is possible
that automatic thoughts either cause the disorder or maintain it, and thus their
examination is warranted. METHOD: 30 SAD subjects diagnosed with the
MiniInternational Neuropsychiatric Interview (MINI) and 30 healthy controls were
administered the Liebowitz Social Anxiety Scale (LSAS), the Automatic Thoughts
Questionnaires (ATQ-Negative and ATQ-Positive), the Sheehan Disability Scale
(SDS) and the Beck Depression Inventory (BDI). It was hypothesized that the SAD
subjects would display more depression and disability, more negative automatic
thoughts and fewer positive automatic thoughts than the healthy controls, and
that the automatic thoughts will predict the severity of SAD. RESULTS: SAD
patients had higher scores of depression and disability, higher scores on the ATQ
Negative questionnaire and lower scores on the ATQ-Positive questionnaire. The
scores of the LSAS subscales were predicted by the scores of the ATQ-Positive and
the BDI questionnaires. LIMITATIONS: Moderate sample size and limits of the
questionnaires used in the study. CONCLUSIONS: Automatic thoughts may be an
important area of research with larger samples. Further studies should be carried
out in order to examine if strengthening positive thinking and ablation of
negative thinking can reduce SAD symptoms during cognitive behavioral treatment.
PMID- 26431419
TI - Voluntary Departure of Family Physicians from their Workplace: A Reflective
Outlook.
AB - OBJECTIVES: The objective of this study was to highlight and assess the important
topic of the voluntary departure of the physician from his/her clinic. We used
the topic of the voluntary departure of a family physician from the clinic as an
example. The physician's leaving challenges the personal credo regarding the
continuity of care, which is a basic concept in Family Medicine, and other
professions, too: Psychiatrists are also devoted to long-term doctor-patient
care. Leaving a place of work is a significant life event that can be accompanied
by stress and even a crisis for the doctor, patients, and staff. METHODS: In this
article, we will present four stories, of four family physicians who voluntarily
left their practices, written from a reflective point of view, either before or
after the actual departure. The stories will be analyzed in a qualitative way,
and the central themes and narratives will be defined. RESULTS: The personal
departure stories revealed important personal and systemic themes that emerge
from and influence the departure process. Among the themes were: practical and
emotional work circumstances; leaving as a grief process; and reactions of
patients, staff, and management. CONCLUSION: Qualitative analysis revealed that
the voluntary departure of the family physician has complex personal and systemic
implications. PRACTICAL IMPLICATIONS: The combination of Balint group discussions
and written reflections can help the physician better cope with the departure and
also help patients and staff deal with the separation process.
PMID- 26431420
TI - Evaluating the Quality of Cardiopulmonary Resuscitation in the Emergency
Department by Real-Time Video Recording System.
AB - OBJECTIVES: To compare cardiopulmonary resuscitation (CPR) quality between manual
CPR and miniaturized chest compressor (MCC) CPR. To improve CPR quality through
evaluating the quality of our clinical work of resuscitation by real-time video
recording system. METHODS: The study was a retrospective observational study of
adult patients who experienced CPR at the emergency department of Shanghai Tenth
People's Hospital from March 2013 to August 2014. All the performance of CPR were
checked back by the record of "digital real-time video recording system". Average
chest compression rate, actual chest compression rate, the percentage of hands
off period, time lag from patient arrival to chest compression, time lag from
patient arrival to manual ventilation, time lag from patient arrival to first IV
establish were compared. Causes of chest compression hands-off time were also
studied. RESULTS: 112 cases of resuscitation attempts were obtained. Average
chest compression rate was over 100 compression per minute (cpm) in the majority
of cases. However, indicators such as percentage of hands-off periods, time lag
from patient arrival to the first manual ventilation and time lag from patient
arrival to the first IV establish seemed to be worse in the manual CPR group
compared to MCC CPR group. The saving of operators change time seemed to
counteract the time spent on MCC equipment. Indicators such as percentage of
hands-off periods, time lag between patient arrival to the first chest
compression, time lag between patient arrival to the first manual ventilation and
time lag from patient arrival to the first IV establish may influence the
survival. CONCLUSION: Our CPR quality remained to be improved. MCC may have a
potentially positive role in CPR.
PMID- 26431421
TI - MAP-Kinase Activated Protein Kinase 2 Links Endothelial Activation and
Monocyte/macrophage Recruitment in Arteriogenesis.
AB - Arteriogenesis, the growth of natural bypass arteries, is triggered by
hemodynamic forces within vessels and requires a balanced inflammatory response,
involving induction of the chemokine MCP-1 and recruitment of leukocytes.
However, little is known how these processes are coordinated. The MAP-kinase
activated-proteinkinase-2 (MK2) is a critical regulator of inflammatory processes
and might represent an important link between cytokine production and cell
recruitment during postnatal arteriogenesis. Therefore, the present study
investigated the functional role of MK2 during postnatal arteriogenesis. In a
mouse model of hindlimb ischemia (HLI) MK2-deficiency (MK2KO) significantly
impaired ischemic blood flow recovery and growth of collateral arteries as well
as perivascular recruitment of mononuclear cells and macrophages. This was
accompanied by induction of endothelial MCP-1 expression in wildtype (WT) but not
in MK2KO collateral arteries. Following HLI, MK2 activation rapidly occured in
the endothelium of growing WT arteries in vivo. In vitro, inflammatory cytokines
and cyclic stretch activated MK2 in endothelial cells, which was required for
stretch- and cytokine-induced release of MCP-1. In addition, a monocyte cell
autonomous function of MK2 was uncovered potentially regulating MCP-1-dependent
monocyte recruitment to vessels: MCP-1 stimulation of WT monocytes induced MK2
activation and monocyte migration in vitro. The latter was reduced in MK2KO
monocytes, while in vivo MK2 was activated in monocytes recruited to collateral
arteries. In conclusion, MK2 regulates postnatal arteriogenesis by controlling
vascular recruitment of monocytes/macrophages in a dual manner: regulation of
endothelial MCP-1 expression in response to hemodynamic and inflammatory forces
as well as MCP-1 dependent monocyte migration.
PMID- 26431422
TI - The role of pain acceptance on function in individuals with disabilities: a
longitudinal study.
AB - Having higher levels of pain acceptance has been shown to be associated
positively with quality of life in patients with chronic pain, but its role in
adjustment to chronic pain among individuals with physical disabilities living in
the community is not known. Moreover, issues related to item overlap between
measures of pain acceptance and measures of patient function have limited the
conclusions that can be drawn from previous research in this area. To better
understand the role that pain acceptance plays in patient function, we
administered measures of pain acceptance, pain intensity, depressive symptoms,
and function to 392 individuals with physical disabilities, and the pain,
symptom, and function measures were readministered 3.5 years later. Analyses
evaluated the main and interaction effects of initial pain acceptance on
subsequent changes in pain and function. Having higher levels of pain acceptance
in particular as reflected by a willingness to engage in activities despite pain
resulted in less increase in pain intensity and more improvements in pain
interference, physical function, depressive symptoms, and sleep quality. The
findings indicate that previous research supporting the importance of pain
acceptance to function in patients from health care settings extends to
individuals with chronic pain living in the community. Moreover, they indicate
that pain acceptance may have long-lasting (up to 3.5 years) beneficial effects
on subsequent pain and function and on the association between change in pain and
depression. Research to examine the potential benefits of community-based
treatments that increase pain acceptance is warranted.
PMID- 26431423
TI - Meta-analytic evidence for decreased heart rate variability in chronic pain
implicating parasympathetic nervous system dysregulation.
AB - Both sympathetic and parasympathetic nervous systems are involved in regulating
pain states. The activity of these systems seems to become disturbed in states of
chronic pain. This disruption in autonomic balance can be measured through the
assessment of heart rate variability (HRV), that is, the variability of the
interval between consecutive heart beats. However, there is yet to be a
systematic evaluation of the body of literature concerning HRV across several
chronic pain conditions. Moreover, modern meta-analytical techniques have never
been used to validate and consolidate the extent to which HRV may be decreased in
chronic pain. Following the preferred reporting items for systematic reviews and
meta-analyses (PRISMA) statement guidelines, this study systematically evaluated
and critically appraised the literature concerning HRV in people living with
chronic pain. After screening 17,350 sources, 51 studies evaluating HRV in a
chronic pain group met the inclusion criteria. Twenty-six moderate-high quality
studies were included in quantitative meta-analyses. On average, the quality of
studies was moderate. There were 6 frequency-domain and time-domain measures of
HRV across a broad range of chronic pain conditions. High heterogeneity aside,
pooled results from the meta-analyses reflected a consistent, moderate-to-large
effect of decreased high-frequency HRV in chronic pain, implicating a decrease in
parasympathetic activation. These effects were heavily influenced by fibromyalgia
studies. Future research would benefit from wider use of standardised definitions
of measurement, and also investigating the synergistic changes in pain state and
HRV throughout the development and implementation of mechanism-based treatments
for chronic pain.
PMID- 26431425
TI - Geminivirus Activates ASYMMETRIC LEAVES 2 to Accelerate Cytoplasmic DCP2-Mediated
mRNA Turnover and Weakens RNA Silencing in Arabidopsis.
AB - Aberrant viral RNAs produced in infected plant cells serve as templates for the
synthesis of dsRNAs. The derived virus-related small interfering RNAs (siRNA)
mediate cleavage of viral RNAs by post-transcriptional gene silencing (PTGS),
thus blocking virus multiplication. Here, we identified ASYMMETRIC LEAVES2 (AS2)
as a new component of plant P body complex which mediates mRNA decapping and
degradation. We found that AS2 promotes DCP2 decapping activity, accelerates mRNA
turnover rate, inhibits siRNA accumulation and functions as an endogenous
suppressor of PTGS. Consistent with these findings, as2 mutant plants are
resistant to virus infection whereas AS2 over-expression plants are
hypersensitive. The geminivirus nuclear shuttle protein BV1 protein, which
shuttles between nuclei and cytoplasm, induces AS2 expression, causes nuclear
exit of AS2 to activate DCP2 decapping activity and renders infected plants more
sensitive to viruses. These principles of gene induction and shuttling of induced
proteins to promote mRNA decapping in the cytosol may be used by viral pathogens
to weaken antiviral defenses in host plants.
PMID- 26431424
TI - Subcellular Partitioning of Protein Tyrosine Phosphatase 1B to the Endoplasmic
Reticulum and Mitochondria Depends Sensitively on the Composition of Its Tail
Anchor.
AB - The canonical protein tyrosine phosphatase PTP1B is an important regulator of
diverse cellular signaling networks. PTP1B has long been thought to exert its
influence solely from its perch on the endoplasmic reticulum (ER); however, an
additional subpopulation of PTP1B has recently been detected in mitochondria
extracted from rat brain tissue. Here, we show that PTP1B's mitochondrial
localization is general (observed across diverse mammalian cell lines) and
sensitively dependent on the transmembrane domain length, C-terminal charge and
hydropathy of its short (<=35 amino acid) tail anchor. Our electron microscopy of
specific DAB precipitation revealed that PTP1B localizes via its tail anchor to
the outer mitochondrial membrane (OMM), with fluorescence lifetime imaging
microscopy establishing that this OMM pool contributes to the previously reported
cytoplasmic interaction of PTP1B with endocytosed epidermal growth factor
receptor. We additionally examined the mechanism of PTP1B's insertion into the ER
membrane through heterologous expression of PTP1B's tail anchor in wild-type
yeast and yeast mutants of major conserved ER insertion pathways: In none of
these yeast strains was ER targeting significantly impeded, providing in vivo
support for the hypothesis of spontaneous membrane insertion (as previously
demonstrated in vitro). Further functional elucidation of the newly recognized
mitochondrial pool of PTP1B will likely be important for understanding its
complex roles in cellular responses to external stimuli, cell proliferation and
diseased states.
PMID- 26431426
TI - Proteomic Characterization of Annexin l (ANX1) and Heat Shock Protein 27 (HSP27)
as Biomarkers for Invasive Hepatocellular Carcinoma Cells.
AB - To search for reliable biomarkers and drug targets for management of
hepatocellular carcinoma (HCC), we performed a global proteomic analysis of a
pair of HCC cell lines with distinct differentiation statuses using 2-DE coupled
with MALDI-TOF MS. In total, 106 and 55 proteins were successfully identified
from the total cell lysate and the cytosolic, nuclear and membrane fractions in
well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) HCC clonal
variants, respectively. Among these proteins, nine spots corresponding to
proteins differentially expressed between HCC cell types were selected and
confirmed by immunofluorescence staining and western blotting. Notably, Annexin 1
(ANX1), ANX-2, vimentin and stress-associated proteins, such as GRP78, HSP75, HSC
70, protein disulfide isomerase (PDI), and heat shock protein-27 (HSP27), were
exclusively up-regulated in SK-Hep-1 cells. Elevated levels of ANX-4 and
antioxidant/metabolic enzymes, such as MnSOD, peroxiredoxin, NADP-dependent
isocitrate dehydrogenase, alpha-enolase and UDP-glucose dehydrogenase, were
observed in HepG2 cells. We functionally demonstrated that ANX1 and HSP27 were
abundantly overexpressed only in highly invasive types of HCC cells, such as
Mahlavu and SK-Hep-1. Knockdown of ANX1 or HSP27 in HCC cells resulted in a
severe reduction in cell migration. The in-vitro observations of ANX1 and HSP27
expressions in HCC sample was demonstrated by immunohistochemical stains
performed on HCC tissue microarrays. Poorly differentiated HCC tended to have
stronger ANX1 and HSP27 expressions than well-differentiated or moderately
differentiated HCC. Collectively, our findings suggest that ANX1 and HSP27 are
two novel biomarkers for predicting invasive HCC phenotypes and could serve as
potential treatment targets.
PMID- 26431427
TI - Improving the Health Forecasting Alert System for Cold Weather and Heat-Waves In
England: A Proof-of-Concept Using Temperature-Mortality Relationships.
AB - OBJECTIVES: In this study a prototype of a new health forecasting alert system is
developed, which is aligned to the approach used in the Met Office's (MO)
National Severe Weather Warning Service (NSWWS). This is in order to improve
information available to responders in the health and social care system by
linking temperatures more directly to risks of mortality, and developing a system
more coherent with other weather alerts. The prototype is compared to the current
system in the Cold Weather and Heatwave plans via a case-study approach to verify
its potential advantages and shortcomings. METHOD: The prototype health
forecasting alert system introduces an "impact vs likelihood matrix" for the
health impacts of hot and cold temperatures which is similar to those used
operationally for other weather hazards as part of the NSWWS. The impact axis of
this matrix is based on existing epidemiological evidence, which shows an
increasing relative risk of death at extremes of outdoor temperature beyond a
threshold which can be identified epidemiologically. The likelihood axis is based
on a probability measure associated with the temperature forecast. The new method
is tested for two case studies (one during summer 2013, one during winter 2013),
and compared to the performance of the current alert system. CONCLUSIONS: The
prototype shows some clear improvements over the current alert system. It allows
for a much greater degree of flexibility, provides more detailed regional
information about the health risks associated with periods of extreme
temperatures, and is more coherent with other weather alerts which may make it
easier for front line responders to use. It will require validation and
engagement with stakeholders before it can be considered for use.
PMID- 26431428
TI - Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain
Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper
Kinase (DLK, MAP3K12).
AB - Recent data suggest that inhibition of dual leucine zipper kinase (DLK, MAP3K12)
has therapeutic potential for treatment of a number of indications ranging from
acute neuronal injury to chronic neurodegenerative disease. Thus, high demand
exists for selective small molecule DLK inhibitors with favorable drug-like
properties and good CNS penetration. Herein we describe a shape-based scaffold
hopping approach to convert pyrimidine 1 to a pyrazole core with improved
physicochemical properties. We also present the first crystal structures of DLK.
By utilizing a combination of property and structure-based design, we identified
inhibitor 11, a potent, selective, and brain-penetrant inhibitor of DLK with
activity in an in vivo nerve injury model.
PMID- 26431429
TI - Bioinformatics Analysis of Proteome Changes in Calu-3 Cell Infected by Influenza
A Virus (H5N1).
AB - AIM: This paper aimed to identify the differentially expressed proteins (DEPs) in
Calu-3 cells infected by influenza A virus (IAV) subtype H5N1. METHODS: We
downloaded proteome data (BTO: 0000762) from the Proteomics Identifications
database and identified the DEPs in the IAV-infected Calu-3 cells. Then we
constructed a protein-protein interaction network and a transcriptional
regulatory network of the proteins. Finally, we performed gene ontology (GO)
analysis to study the IAV infection at a functional level. RESULTS: A total of 4
protein groups between the normal cells and the Calu-3 cells infected by IAV,
severe acute respiratory syndrome or swine influenza were identified. In the
networks, we found 5 significant proteins including FAN, CPSF2, AGO1, AGO2 and
PAX5. In addition, we demonstrated those proteins were associated with GO terms
such as phosphate metabolic process, calcium ion transport, cell division and
regulation of cell motion. STAT1, NS2, CD5, NCKX6 and PDGFB were significant DEPs
in these GO terms. CONCLUSIONS: By referring to the previous studies, we suggest
that proteins including FAN, CPSF2, AGO1, AGO2, PAX5, STAT1 and PDGFB can be used
as therapeutic targets of IAV infection.
PMID- 26431430
TI - The Global Cognition, Frontal Lobe Dysfunction and Behavior Changes in Chinese
Patients with Multiple System Atrophy.
AB - BACKGROUND: Studies on cognition in multiple system atrophy (MSA) patients are
limited. METHODS: A total of 110 MSA patients were evaluated using Addenbrooke's
Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), Frontal
Behavioral Inventory (FBI), and Unified MSA Rating Scale (UMSARS) tests. Fifty
five age-, sex-, education- and domicile-matched healthy controls were recruited
to perform the FAB and ACE-R scales. RESULTS: Approximately 32.7% of the patients
had global cognitive deficits with the most impaired domain being verbal fluency
and visuospatial ability (26.4%), followed by memory (24.5%), language (20%) and
orientation/attention (20%) based on a cut-off score of ACE-R <= 70. A total of
41.6% of the patients had frontal lobe dysfunction, with inhibitory control
(60.9%) as the most impaired domain based on a cut-off score of FAB <=14. Most
patients (57.2%) showed moderate frontal behavior changes (FBI score 4-15), with
incontinence (64.5%) as the most impaired domain. The binary logistic regression
model revealed that an education level < 9 years (OR:13.312, 95% CI:2.931-60.469,
P = 0.001) and UMSARS >= 40 (OR: 2.444, 95%CI: 1.002-5.962, P< 0.049) were
potential determinants of abnormal ACE-R, while MSA-C (OR: 4.326, 95%CI: 1.631
11.477, P = 0.003), an education level < 9 years (OR:2.809 95% CI:1.060-7.444, P
= 0.038) and UMSARS >= 40 (OR:5.396, 95%CI: 2.103-13.846, P < 0.0001) were
potential determinants of abnormal FAB. CONCLUSIONS: Cognitive impairment is
common in Chinese MSA patients. MSA-C patients with low education levels and
severe motor symptoms are likely to experience frontal lobe dysfunction, while
MSA patients with low education levels and severe motor symptoms are likely to
experience global cognitive deficits. These findings strongly suggest that
cognitive impairment should not be an exclusion criterion for the diagnosis of
MSA.
PMID- 26431431
TI - Effects of Omega-3 Fatty Acid Supplementation on Glucose Control and Lipid Levels
in Type 2 Diabetes: A Meta-Analysis.
AB - BACKGROUND: Many studies assessed the impact of marine omega-3 fatty acids on
glycemic homeostasis and lipid profiles in patients with type 2 diabetes (T2DM),
but reported controversial results. Our goal was to systematically evaluate the
effects of omega-3 on glucose control and lipid levels. METHODS: Medline, Pubmed,
Cochrane Library, Embase, the National Research Register, and SIGLE were searched
to identify eligible randomized clinical trials (RCTs). Extracted data from RCTs
were analyzed using STATA 11.0 statistical software with fixed or random effects
model. Effect sizes were presented as weighted mean differences (WMD) with 95%
confidence intervals (95% CI). Heterogeneity was assessed using the Chi-square
test with significance level set at p < 0.1. RESULTS: 20 RCT trials were included
into this meta-analysis. Among patients with omega-3 supplementation,
triglyceride (TG) levels were significantly decreased by 0.24 mmol/L. No marked
change in total cholesterol (TC), HbA1c, fasting plasma glucose, postprandial
plasma glucose, BMI or body weight was observed. High ratio of EPA/DHA
contributed to a greater decreasing tendency in plasma insulin, HbAc1, TC, TG,
and BMI measures, although no statistical significance was identified (except
TG). FPG levels were increased by 0.42 mmol/L in Asians. No evidence of
publication bias was observed in this meta-analysis. CONCLUSIONS: The ratio of
EPA/DHA and early intervention with omega 3 fatty acids may affect their effects
on glucose control and lipid levels, which may serve as a dietary reference for
clinicians or nutritionists who manage diabetic patients.
PMID- 26431432
TI - Persons with Haemophilia in Sweden- Experiences and Strategies in Everyday Life.
A Single Centre Study.
AB - INTRODUCTION/AIM: Haemophilia is caused by deficiency in coagulation factor VIII
or IX. Treatment with the missing coagulation factors has been available in most
developed countries for several decades. The aim was to explore the experiences
of adults living with severe or moderate haemophilia and their coping strategies
at a single centre in Sweden. METHOD: The interview study had a qualitative
empirical approach and was analyzed on the basis of the method empirical
phenomenological psychology. The sample included 14 participants, mean age 42 (19
80 y), who met the inclusion criteria and to saturation of information. RESULTS:
General characteristics were; All were satisfied with and grateful for access to
medication. An acceptance of the disorder and willingness to live a normal life
was identified among all participants. They were all content with the care
provided by Haemophilia Treatment Centre (HTC) and felt supported by its
multidisciplinary team. Four typologies were identified; Protective adults and
assertive children during up-bringing, finding a role in social context, symptoms
and treatments, fear of limited resources in the future. Task-, emotional- and
avoidance coping strategies were seen in the interviews. The most prominent
coping strategy was task oriented. CONCLUSION: This interview study with Swedish
PWH shows that they strive for normality and adaptation in social activities
throughout life finding their own niche. The PWH expressed the importance of
knowledge and support from the comprehensive medical team at HTC and therefore it
seems important to continue comprehensive medical care at HTC in order to follow
up the haemophilia persons regularly.
PMID- 26431434
TI - Performance Evaluation of the Verigene Gram-Positive and Gram-Negative Blood
Culture Test for Direct Identification of Bacteria and Their Resistance
Determinants from Positive Blood Cultures in Hong Kong.
AB - BACKGROUND: A multicenter study was conducted to evaluate the diagnostic
performance and the time to identifcation of the Verigene Blood Culture Test, the
BC-GP and BC-GN assays, to identify both Gram-positive and Gram-negative bacteria
and their drug resistance determinants directly from positive blood cultures
collected in Hong Kong. METHODS AND RESULTS: A total of 364 blood cultures were
prospectively collected from four public hospitals, in which 114 and 250 cultures
yielded Gram-positive and Gram-negative bacteria, and were tested with the BC-GP
and BC-GN assay respectively. The overall identification agreement for Gram
positive and Gram-negative bacteria were 89.6% and 90.5% in monomicrobial
cultures and 62.5% and 53.6% in polymicrobial cultures, respectively. The
sensitivities for most genus/species achieved at least 80% except Enterococcus
spp. (60%), K.oxytoca (0%), K.pneumoniae (69.2%), whereas the specificities for
all targets ranged from 98.9% to 100%. Of note, 50% (7/14) cultures containing
K.pneumoniae that were missed by the BC-GN assay were subsequently identified as
K.variicola. Approximately 5.5% (20/364) cultures contained non-target organisms,
of which Aeromonas spp. accounted for 25% and are of particular concern. For drug
resistance determination, the Verigene test showed 100% sensitivity for
identification of MRSA, VRE and carbapenem resistant Acinetobacter, and 84.4% for
ESBL-producing Enterobacteriaceae based on the positive detection of mecA, vanA,
blaOXA and blaCTXM respectively. CONCLUSION: Overall, the Verigene test provided
acceptable accuracy for identification of bacteria and resistance markers with a
range of turnaround time 40.5 to 99.2 h faster than conventional methods in our
region.
PMID- 26431436
TI - Bone Morphogenetic Protein-7 Inhibits EMT-Associated Genes in Breast Cancer.
AB - BACKGROUND/AIMS: Bone morphogenetic protein-7 (BMP7) has been shown to reduce the
severity of injury-induced fibrosis through counteracting the fibrotic effects of
transforming growth factor beta 1 (TGFbeta1). However, this model in the
carcinogenesis of breast cancer is unknown. METHODS: We analyzed the effects of
BMP7 and TGFbeta1 on gene transcripts and protein levels of EMT-related factors
in breast cancer cells by RT-qPCR and Western blot, respectively. The effects of
BMP7 and TGFbeta1 on cell invasiveness and migration were evaluated by scratch
wound healing assay and transwell cell migration assay. The cell growth was
measured by MTT assay. RESULTS: BMP7 did not alter the TGFbeta1-stimulated
phosphorylation of TGFbeta receptor, but significantly inhibited the TGFbeta1
activated epithelial-mesenchymal transition (EMT)-related genes in breast cancer
cells, resulting in a significant reduction in TGFbeta1-triggered cell growth and
cell metastasis. CONCLUSION: Our data suggest that besides being a well-known
antagonist for TGFbeta1 in fibrosis, BMP7 may also antagonize TGFbeta1 in
tumorigenesis-associated EMT in breast cancer. Thus, BMP7 may be a promising
therapeutic target for treating breast cancer.
PMID- 26431433
TI - The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid
Secretion.
AB - The Endosomal Sorting Complex Required for Transport (ESCRT) is an important
cellular machinery for the sorting and trafficking of ubiquitinated cargos. It is
also known that ESCRT is required for the egress of a number of viruses. To
investigate the relationship between ESCRT and hepatitis B virus (HBV), we
conducted an siRNA screening of ESCRT components for their potential effect on
HBV replication and virion release. We identified a number of ESCRT factors
required for HBV replication, and focused our study here on HGS (HRS, hepatocyte
growth factor-regulated tyrosine kinase substrate) in the ESCRT-0 complex.
Aberrant levels of HGS suppressed HBV transcription, replication and virion
secretion. Hydrodynamic delivery of HGS in a mouse model significantly suppressed
viral replication in the liver and virion secretion in the serum. Surprisingly,
overexpression of HGS stimulated the release of HBV naked capsids, irrespective
of their viral RNA, DNA, or empty contents. Mutant core protein (HBc 1-147)
containing no arginine-rich domain (ARD) failed to secrete empty virions with or
without HGS. In contrast, empty naked capsids of HBc 1-147 could still be
promoted for secretion by HGS. HGS exerted a strong positive effect on the
secretion of naked capsids, at the expense of a reduced level of virions. The
association between HGS and HBc appears to be ubiquitin-independent. Furthermore,
HBc is preferentially co-localized with HGS near the cell periphery, instead of
near the punctate endosomes in the cytoplasm. In summary, our work demonstrated
the importance of an optimum level of HGS in HBV propagation. In addition to an
effect on HBV transcription, HGS can diminish the pool size of intracellular
nucleocapsids with ongoing genome maturation, probably in part by promoting the
secretion of naked capsids. The secretion routes of HBV virions and naked capsids
can be clearly distinguished based on the pleiotropic effect of HGS involved in
the ESCRT-0 complex.
PMID- 26431435
TI - On the Computing Potential of Intracellular Vesicles.
AB - Collision-based computing (CBC) is a form of unconventional computing in which
travelling localisations represent data and conditional routing of signals
determines the output state; collisions between localisations represent logical
operations. We investigated patterns of Ca2+-containing vesicle distribution
within a live organism, slime mould Physarum polycephalum, with confocal
microscopy and observed them colliding regularly. Vesicles travel down
cytoskeletal 'circuitry' and their collisions may result in reflection, fusion or
annihilation. We demonstrate through experimental observations that naturally
occurring vesicle dynamics may be characterised as a computationally-universal
set of Boolean logical operations and present a 'vesicle modification' of the
archetypal CBC 'billiard ball model' of computation. We proceed to discuss the
viability of intracellular vesicles as an unconventional computing substrate in
which we delineate practical considerations for reliable vesicle 'programming' in
both in vivo and in vitro vesicle computing architectures and present optimised
designs for both single logical gates and combinatorial logic circuits based on
cytoskeletal network conformations. The results presented here demonstrate the
first characterisation of intracelluar phenomena as collision-based computing and
hence the viability of biological substrates for computing.
PMID- 26431437
TI - Villitis of unknown aetiology: Clinical implications in preterm population.
AB - Villitis of unknown aetiology (VUE) is a chronic inflammatory process of
chorionic villi which is reported to occur in up to 15% of term placentas. The
present study aimed to investigate the association between VUE and perinatal
complications in a population who delivered before term. Patients with VUE had a
significantly higher rate of intrauterine growth restriction than the control
group (47.1% vs. 20.6%, p < 0.01). In addition patients with VUE had a higher
rate of deliveries due to absent diastolic flow on umbilical artery doppler than
the control group (17.6% vs. 4.4%, p: 0.03). The rate of spontaneous preterm
birth or pre-eclampsia was similar in patients with VUE and control groups. The
present study provides some evidence that VUE is associated with abnormal
perinatal outcomes in pregnant women who give birth before term.
PMID- 26431438
TI - Cancer survivors face steep economic burdens: Excessive medical expenses and loss
of productivity at work plague some, even years after initial diagnosis.
PMID- 26431439
TI - Immunotherapy drug improves survival of patients with squamous non-small cell
lung cancer.
PMID- 26431440
TI - Diastolic dysfunction common among breast cancer patients receiving
anthracycline.
PMID- 26431444
TI - Synthesis, Photophysics, and Self-Assembly of Furan-Embedded Heteroarenes.
AB - A series of pyrene/phenanthrene-fused furan derivatives (1-8) were synthesized by
a simple condensation reaction between pyrene-4,5-diketone/phenanthrenequinone
and substituted phenol/naphthol in the presence of trifluoromethanesulfonic acid
in 1,2-dichlorobenzene heated at reflux. The formed compounds can emit strong
blue light in organic solvents. Additionally, the self-assembly behaviors of two
of the compounds (3 and 5) were studied through re-precipitation method and the
resulting nanostructures were characterized by UV/Vis, fluorescence spectra, and
field-emission scanning electron microscopy (FESEM). The findings showed that the
shape and size of compounds 3 and 5 could be tuned by the ratio of THF and
hexadecyl trimethyl ammonium bromide (CTAB) solution in water.
PMID- 26431447
TI - Folivory as a Constraint on Social Behaviour of Langurs in South India.
AB - Folivory, being a dietary constraint, can affect the social time of colobines. In
the present study, we compared food items and activity budgets of two closely
related species of colobines inhabiting South India, i.e. the Hanuman langur
(Semnopithecus hypoleucos) and Nilgiri langur (Semnopithecus johnii), to
determine whether folivory had an impact on social time in these species. Our
study established that Nilgiri langurs were more folivorous than Hanuman langurs.
Nilgiri langurs spent much less time on social activities, but more time on
resting, although the social organization of S. hypoleucos was similar to that of
the Nilgiri langur. The enforced resting time for fermentation of leafy food
items may have reduced the time available for social interactions, which in turn
affected the social time in Nilgiri langurs. By comparing the data from previous
studies on other Hanuman langur species, we found that S. hypoleucos spent a
similar amount of time on social activities as Semnopithecus entellus. Hence, the
social behaviour of S. entellus and S. hypoleucos is phylogenetically highly
conservative.
PMID- 26431448
TI - Management of oromandibular dystonia on a chorea acanthocytosis: a brief review
of the literature and a clinical case.
AB - BACKGROUND: Chorea acanthocytosis is an extremely rare neurodegenerative
condition characterized by neuropsychiatric disturbances, movement disorders,
neuropathy, seizures, and acanthocytosis. In this case report, the authors will
present the management of the oromandibular movement disorders associated with
this disease. CASE DESCRIPTION: This case report describes the focal management
of the severe orofacial manifestations associated with this condition. The
therapeutic approach adopted to reduce the severe oromandibular movements,
dysphagia, and the numerous oral ulcers was selective electromyography (EMG)
guided botulinum toxin application to the inferior head of the lateral pterygoid
muscles and masseters. This would be applied to control severe and sudden
oromandibular dystonia. RESULTS: Through this procedure, the authors were able to
reduce these severe oral manifestations, which had a major impact on the
patient's quality of life, and temporarily improve vital functions, such as
mastication, deglutition, and speech articulation. CONCLUSIONS: Electromyography
guided botulinum toxin application may be a useful tool in the multimodal
management of this condition.
PMID- 26431449
TI - Benzylic C-H trifluoromethylation of phenol derivatives.
AB - Phenol derivatives were trifluoromethylated using copper/Togni reagent. In
dimethylformamide, the benzylic C-H bond at the para position of the hydroxyl
group was selectively substituted with a CF3 group. In contrast, aromatic C-H
trifluoromethylation occurred in alcoholic solvents. Practical utility of the
reactions was demonstrated by application to the synthesis of a potent enoyl-acyl
carrier protein reductase (FabI) inhibitor.
PMID- 26431450
TI - Equisetin, reutericyclin and streptolodygin as natural product lead structures
for novel antibiotic libraries.
AB - The emergence of antimicrobial resistance has created a need for the development
of novel antibacterial therapies to treat infection. Natural products that
exhibit antibacterial activity offer validated starting points for library
generation, and the authors report here that small molecule mimics of tetramate
containing natural products may show antibacterial activity and offer the
potential for further optimization.
PMID- 26431451
TI - Demodicosis in Renal Transplant Recipients.
AB - Solid organ transplant recipients have an increased incidence of skin infections
resulting from immunosuppression. Common pathogens include herpes simplex virus,
varicella zoster virus, Gram-positive bacteria and dermatophytes; however, the
contribution of multicellular parasitic organisms to dermatologic disease in this
population remains less studied. Demodex folliculorum and brevis are commensal
mites that reside on human skin. Proliferation of Demodex mites, or demodicosis,
is associated with rosacea and rosacea-like disorders, particularly in
immunocompromised populations, although their ability to cause disease is still
the subject of debate. We present a case series of four renal transplant
recipients with the singular chief complaint of acne rosacea who we diagnosed
with demodicosis. Although one of the four patients showed complete resolution
following initial antiparasitic therapy, the other three required subsequent
antibacterial treatment to fully resolve their lesions. We suggest that
demodicosis may be more prevalent than once thought in solid organ transplant
recipients and showed that Demodex-associated acne rosacea can be effectively
treated in this population.
PMID- 26431456
TI - Fixed-dose combination products and unintended drug interactions: urgent need for
pharmacogenetic evaluation.
PMID- 26431457
TI - The effect of NaCl on stomatal opening in Arabidopsis wild type and agb1
heterotrimeric G-protein mutant plants.
AB - Salinity is a major agricultural problem that affects crop yield. Na(+) is
transported to the shoot through the transpiration stream. The mutant of the sole
Arabidopsis heterotrimeric G protein beta subunit, agb1, is hypersensitive to
salinity in part due to a higher transpiration rate. Here, we investigated the
direct effect of Na(+) on stomatal opening using detached epidermal peels of wild
type and agb1 plants. In both genotypes, NaCl is equally as effective as KCl in
mediating stomatal opening at the concentrations tested. In both genotypes, ABA
is less effective in inhibiting Na(+) mediated stomatal opening than K(+)
mediated stomatal opening. The agb1 mutant is hyposensitive to ABA inhibition of
K(+)-mediated but not Na(+)-mediated stomatal opening. These results suggest that
the greater transpiration observed in agb1 plants grown in saline conditions is
likely not mediated by differential genotypic direct effects of Na(+) on stomatal
apertures.
PMID- 26431458
TI - Change in Quality of Life for Patients with Irritable Bowel Syndrome following
Referral to a Gastroenterologist: A Cohort Study.
AB - BACKGROUND: Irritable bowel syndrome (IBS), a chronic functional condition,
considerably reduces quality of life (QoL) and referral to gastroenterology is
common. Until now, however, the impact of seeing a gastroenterologist for IBS on
patients' QoL and utility has not been assessed. METHODS: Patients referred with
"probable IBS" to the Nottingham Treatment Centre between October 2012 and March
2014 were invited to complete a QoL questionnaire (EuroQol-5 Dimension) before
their first appointment. Patients with confirmed IBS who completed this baseline
assessment were sent follow-up questionnaires three and twelve months later.
Global QoL and utility were measured at each time point and change from baseline
calculated. Paired t-tests analysed the significance of any change. RESULTS: Of
205 invited patients, 69 were eligible and recruited. Response at three and
twelve months was 45% and 17% respectively. Median global QoL at baseline was
67.5 (Interquartile range [IQR] 50.0 to 80.0), with a mean increase of 3.25 (95%
confidence interval [CI] -5.38 to 11.88) three months later and a mean decrease
of -1.82 (95% CI -16.01 to 12.38) after one year. The median utility at baseline
was 0.76 (IQR 0.69 to 0.80), with a mean increase of 0.06 (95%CI -0.01 to 0.14)
at three months and no change, 0.00 (-0.16 to 0.16), after one year. CONCLUSION:
Patients experienced a small but not statistically significant increase in QoL
and utility three months after seeing a gastroenterologist for IBS, which was not
maintained. Gastroenterology referral does not appear to appreciably improve Qol
for most people with IBS.
PMID- 26431462
TI - Kinetics of hematopoietic stem cells and supportive activities of stromal cells
in a three-dimensional bone marrow culture system.
AB - In the bone marrow, hematopoietic cells proliferate and differentiate in close
association with a three-dimensional (3D) hematopoietic microenvironment.
Previously, we established a 3D bone marrow culture system. In this study, we
analyzed the kinetics of hematopoietic cells, and more than 50% of hematopoietic
progenitor cells, including CFU-Mix, CFU-GM and BFU-E in 3D culture were in a
resting (non-S) phase. Furthermore, we examined the hematopoietic supportive
ability of stromal cells by measuring the expression of various mRNAs relevant to
hematopoietic regulation. Over the 4 weeks of culture, the stromal cells in the
3D culture are not needlessly activated and "quietly" regulate hematopoietic cell
proliferation and differentiation during the culture, resulting in the presence
of resting hematopoietic stem cells in the 3D culture for a long time. Thus, the
3D culture system may be a new tool for investigating hematopoietic stem cell
stromal cell interactions in vitro.
PMID- 26431463
TI - ncRDeathDB: A comprehensive bioinformatics resource for deciphering network
organization of the ncRNA-mediated cell death system.
AB - Programmed cell death (PCD) is a critical biological process involved in many
important processes, and defects in PCD have been linked with numerous human
diseases. In recent years, the protein architecture in different PCD subroutines
has been explored, but our understanding of the global network organization of
the noncoding RNA (ncRNA)-mediated cell death system is limited and ambiguous.
Hence, we developed the comprehensive bioinformatics resource (ncRDeathDB,
www.rna-society.org/ncrdeathdb ) to archive ncRNA-associated cell death
interactions. The current version of ncRDeathDB documents a total of more than
4600 ncRNA-mediated PCD entries in 12 species. ncRDeathDB provides a user
friendly interface to query, browse and manipulate these ncRNA-associated cell
death interactions. Furthermore, this resource will help to visualize and
navigate current knowledge of the noncoding RNA component of cell death and
autophagy, to uncover the generic organizing principles of ncRNA-associated cell
death systems, and to generate valuable biological hypotheses.
PMID- 26431464
TI - Declining trend of Plasmodium falciparum dihydrofolate reductase (dhfr) and
dihydropteroate synthase (dhps) mutant alleles after the withdrawal of
Sulfadoxine-Pyrimethamine in North Western Ethiopia.
AB - Antimalarial drug resistance is one of the major challenges in global efforts of
malaria control and elimination. In 1998, chloroquine was abandoned and replaced
with sulfadoxine/pyrimethamine, which in turn was replaced with
artemether/lumefantrine for the treatment of uncomplicated falciparum malaria in
2004. Sulfadoxine/pyrimethamine resistance is associated with mutations in
dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes. The
prevalence of mutation in Pfdhfr and Pfdhps genes were evaluated and compared for
a total of 159 isolates collected in two different time points, 2005 and 2007/08,
from Pawe hospital, in North Western Ethiopia. The frequency of triple Pfdhfr
mutation decreased significantly from 50.8% (32/63) to 15.9% (10/63) (P<0.001),
while Pfdhps double mutation remained high and changed only marginally from 69.2%
(45/65) to 55.4% (40/65) (P = 0.08). The combined Pfdhfr/Pfdhps quintuple
mutation, which is strongly associated with sulfadoxine/pyrimethamine resistance,
was significantly decreased from 40.7% (24/59) to 13.6% (8/59) (P<0.0001). On the
whole, significant decline in mutant alleles and re-emergence of wild type
alleles were observed. The change in the frequency is explained by the reduction
of residual drug-resistant parasites caused by the strong drug pressure imposed
when sulfadoxine/pyrimethamine was the first-line drug, followed by lower fitness
of these resistant parasites in the absence of drug pressure. Despite the
decrease in the frequency of mutant alleles, higher percentages of mutation
remain prevalent in the study area in 2007/08 in both Pfdhfr and Pfdhps genes.
Therefore, further multi-centered studies in different parts of the country will
be required to assess the re-emergence of sulfadoxine/pyrimethamine sensitive
parasites and to monitor and prevent the establishment of multi drug resistant
parasites in this region.
PMID- 26431465
TI - A Dye-Decolorizing Peroxidase from Vibrio cholerae.
AB - The dye-decolorizing peroxidase (DyP) protein from Vibrio cholerae (VcDyP) was
expressed in Escherichia coli, and its DyP activity was assayed by monitoring
degradation of a typical anthraquinone dye, reactive blue 19 (RB19). Its kinetic
activity was obtained by fitting the data to the Michaelis-Menten equation,
giving kcat and Km values of 1.3 +/- 0.3 s(-1) and 50 +/- 20 MUM, respectively,
which are comparable to those of other DyP enzymes. The enzymatic activity of
VcDyP was highest at pH 4. A mutational study showed that two distal residues,
Asp144 and Arg230, which are conserved in a DyP family, are essential for the DyP
reaction. The crystal structure and resonance Raman spectra of VcDyP indicate the
transfer of a radical from heme to the protein surface, which was supported by
the formation of the intermolecular covalent bond in the reaction with H2O2. To
identify the radical site, each of nine tyrosine or two tryptophan residues was
substituted. It was clarified that Tyr129 and Tyr235 are in the active site of
the dye degradation reaction at lower pH, while Tyr109 and Tyr133 are the sites
of an intermolecular covalent bond at higher pH. VcDyP degrades RB19 at lower pH,
while it loses activity under neutral or alkaline conditions because of a change
in the radical transfer pathway. This finding suggests the presence of a pH
dependent switch of the radical transfer pathway, probably including His178.
Although the physiological function of the DyP reaction is unclear, our findings
suggest that VcDyP enhances the DyP activity to survive only when it is placed
under a severe condition such as being in gastric acid.
PMID- 26431466
TI - Safety and immunogenicity of influenza vaccine among HIV-infected adults:
Conventional vaccine vs. intradermal vaccine.
AB - Several studies have reported poor immune responses to conventional influenza
vaccines in HIV-infected individuals. This study sought to elicit more potent
immunogenicity in HIV-infected adults using an intradermal vaccine compared with
a conventional intramuscular vaccine. This multicenter, randomized, controlled,
open-label study was conducted at 3 university hospitals during the 2011/2012 pre
influenza season. Three vaccines were used in HIV-infected adults aged 18 - 60
years: an inactivated intramuscular vaccine (Agrippal), a reduced-content
intradermal vaccine (IDflu9MUg) and a standard-content intradermal vaccine
(IDflu15MUg). Serum hemagglutination-inhibiting (HI) antibodies and INF-gamma
ELISpot assay were measured at the time of vaccination and 1 month after
vaccination. Adverse events were recorded for 7 d. A total of 28 Agrippal, 30
IDflu9MUg, and 28 IDflu15MUg volunteers were included in this analysis. One month
after vaccination, the GMTs and differences in INF-gamma ELISpot assay results
were similar among the 3 groups. Seroprotection rates, seroconversion rates and
mean fold increases (MFI) among the 3 groups were also similar, at approximately
80%, 50-60% and 2.5 - 10.0, respectively. All three vaccines satisfied the CHMP
criteria for the A/H1N1 and A/H3N2 strains, but not those for the B strain. In
univariate analysis, no demographic or clinical factors, including age, CD4+ T
cell counts, HIV viral load, ART status and vaccine type, were related to failure
to achieve seroprotection. The three vaccines were all well-tolerated and all
reported reactions were mild to moderate. However, there was a tendency toward a
higher incidence of local and systemic reactions in the intradermal vaccine
groups. The intradermal vaccine did not result in higher immunogenicity compared
to the conventional intramuscular vaccine, even with increased antigen dose.
PMID- 26431467
TI - Resonance Raman and vibrational mode analysis used to predict ligand geometry for
docking simulations of a water soluble porphyrin and tubulin.
AB - The ability to modify the conformation of a protein by controlled partial
unfolding may have practical applications such as inhibiting its function or
providing non-native photosensitive properties. A water-soluble porphyrin, meso
tetrakis (p-sulfonatophenyl) porphyrin (TSPP), non-covalently bound to tubulin
can be used as a photosensitizer, which upon irradiation can lead to
conformational changes of the protein. To fully understand the mechanism
responsible for this partial unfolding and determine the amino acid residues and
atoms involved, it is essential to find the most likely binding location and the
configuration of the ligand and protein. Techniques typically used to analyze
atomic position details, such as nuclear magnetic resonance and X-ray
crystallography, require large concentrations, which are incompatible with the
dilute conditions required in experiments for photoinduced mechanisms. Instead,
we develop an atomistic description of the TSPP-tubulin complex using vibrational
mode analysis from density functional theory calculations correlated to resonance
Raman spectra of the porphyrin paired with docking simulations. Changes in the
Raman peaks of the porphyrin molecule correlate with changes in its structural
vibrational modes when bound to tubulin. The data allow us to construct the
relative geometry of the porphyrin when bound to protein, which are then used
with docking simulations to find the most likely configuration of the TSPP
tubulin complex.
PMID- 26431468
TI - The State of Health in Older Adults in Japan: Trends in Disability, Chronic
Medical Conditions and Mortality.
AB - Both life expectancy and healthy life expectancy in Japan have been increasing
and are among the highest in the world, but the gap between them has also been
widening. To examine the recent trends in old age disability, chronic medical
conditions and mortality in Japan, we retrospectively analyzed three nationally
representative datasets: Comprehensive Survey of Living Conditions (2001-2013),
Patient Survey (1996-2011) and Vital Statistics (1995-2010). We obtained the sex-
and age-stratified trends in disability rate, treatment rates of nine selected
chronic medical conditions (cerebrovascular diseases, joint disorders, fractures,
osteoporosis, ischemic heart disease, diabetes mellitus, hypertension, pneumonia
and malignant neoplasms), total mortality rate and mortality rates from specific
causes (cerebrovascular diseases, heart diseases, pneumonia and malignant
neoplasms) in both sexes in four age strata (65-69, 70-74, 75-79, 80-84 years).
Disability rates declined significantly in both sexes. Treatment rates of all
selected medical conditions also decreased significantly, except for fractures in
women and pneumonia. Both total mortality rate and cause-specific mortality rates
decreased in both sexes. We concluded that the recent decline in disability
rates, treatment rates of chronic medical conditions and mortality rates points
toward overall improvement in health conditions in adults over the age of 65
years in Japan. Nonetheless, considering the increase in the number of older
adults, the absolute number of older adults with disability or chronic medical
conditions will continue to increase and challenge medical and long-term care
systems.
PMID- 26431470
TI - Safety, tolerability and pharmacokinetics of multiple oral doses of AFN-1252
administered as immediate release (IR) tablets in healthy subjects.
AB - BACKGROUND: AFN-1252 is a novel inhibitor of FabI, which is essential in
Staphylococcus spp. This study evaluated the safety, tolerability and
pharmacokinetics of multiple oral doses of AFN-1252 immediate-release tablets.
METHODS: Part I evaluated AFN-1252 as a single 200 mg dose in fed versus fasted
subjects. Part II evaluated 200, 300 and 400 mg doses of AFN-1252 administered
once-daily for 10 days. RESULTS: Pharmacokinetics indicated good absorption with
a median Tmax of 2-3 hours, and a mean t1/2 of 7-10 hours, for all doses. Cmax
and AUC responses were non-linear. A high-fat meal reduced AUC0-t and Cmax values
by 62% and 48%, respectively, and delayed Tmax by 2.5 hours. All adverse events,
including possibly drug-related headache and nausea, were mild or moderate.
CONCLUSIONS: Multiple ascending doses of AFN-1252 were safe and well tolerated.
AFN-1252 has potential for once- or twice-daily dosing in the treatment of
staphylococcal infections.
PMID- 26431469
TI - A Western dietary pattern is associated with overweight and obesity in a national
sample of Lebanese adolescents (13-19 years): a cross-sectional study.
AB - Adolescent obesity is associated with both immediate and longer-term health
implications. This study aims to identify dietary patterns among a nationally
representative sample of Lebanese adolescents aged between 13 and 19 years (n
446) and to assess the association of these patterns with overweight and obesity.
Through face-to-face interviews, socio-demographic, lifestyle and anthropometric
variables were collected. Dietary intake was assessed using a sixty-one-item FFQ.
Dietary patterns were derived by factor analysis. The following two dietary
patterns were identified: Western and traditional Lebanese. The Western pattern
was characterised by high consumption of red meat, eggs and fast-food sandwiches.
The traditional Lebanese pattern reflected high intakes of fruits and vegetables,
legumes and fish. Female sex and a higher maternal education level were
associated with a greater adherence to the traditional Lebanese pattern. As for
the Western pattern, the scores were negatively associated with crowding index,
physical activity and frequency of breakfast consumption. After adjustment,
subjects belonging to the 3rd tertile of the Western pattern scores had
significantly higher odds of overweight compared with those belonging to the 1st
tertile (OR 2.3; 95% CI 1.12, 4.73). In conclusion, two distinct dietary patterns
were identified among adolescents in Lebanon: the traditional Lebanese and the
Western, with the latter pattern being associated with an increased risk of
overweight. The findings of this study may be used to guide the development of
evidence-based preventive nutrition interventions to curb the obesity epidemic in
this age group.
PMID- 26431471
TI - Indices of central and general obesity and cardiometabolic risk among adolescents
in three ethnic groups in north-west China.
AB - BACKGROUND: 'A Body Shape Index-Adolescents' (ABSI-Adolescents) and waist-to
height ratio are recently proposed indices that quantify central obesity in
adolescents. AIMS: To investigate the scaling exponents to standardise waist
circumference (WC) for body mass index (BMI) and height and to investigate the
association between BMI, WC-based indices and cardiometabolic outcomes in
adolescents of three ethnic groups. SUBJECTS AND METHODS: A cross-sectional study
of 1755 adolescents (516 Hans, 565 Uygurs, 674 Kazakhs) was conducted in north
west China. Correlation between indices of obesity and blood pressure (BP) and
fasting blood glucose (FBG) were estimated and compared. RESULTS: Two ethnic
groups (Han and Kazakh) had WC-BMI-height profiles different from the previously
proposed ABSI-Adolescents and, therefore, required different scaling exponents
for WC standardization. After adjustment for age and gender, WC and BMI have
similar associations with BP and FBG. After further adjustment for BMI, WC
remained significantly associated with FBG in all three ethnic groups (each p <
0.01) and with BP in Han and Kazakh adolescents (each p < 0.05). CONCLUSION: Body
proportionality varied between the ethnic groups. WC and WC-based indices were
associated with blood pressure and fasting blood glucose in adolescents of three
ethnicities. The WC-based indices did not out-perform WC per se.
PMID- 26431472
TI - Route to the Smallest Doped Semiconductor: Mn(2+)-Doped (CdSe)13 Clusters.
AB - Doping semiconductor nanocrystals with magnetic transition-metal ions has
attracted fundamental interest to obtain a nanoscale dilute magnetic
semiconductor, which has unique spin exchange interaction between magnetic spin
and exciton. So far, the study on the doped semiconductor NCs has usually been
conducted with NCs with larger than 2 nm because of synthetic challenges. Herein,
we report the synthesis and characterization of Mn(2+)-doped (CdSe)13 clusters,
the smallest doped semiconductors. In this study, single-sized doped clusters are
produced in large scale. Despite their small size, these clusters have
semiconductor band structure instead of that of molecules. Surprisingly, the
clusters show multiple excitonic transitions with different magneto-optical
activities, which can be attributed to the fine structure splitting. Magneto
optically active states exhibit giant Zeeman splittings up to elevated
temperatures (128 K) with large g-factors of 81(+/-8) at 4 K. Our results present
a new synthetic method for doped clusters and facilitate the understanding of
doped semiconductor at the boundary of molecules and quantum nanostructure.
PMID- 26431473
TI - Integrated photoacoustic and diffuse optical tomography system for imaging of
human finger joints in vivo.
AB - In this study, we developed a dual-modality tomographic system that integrated
photoacoustic imaging (PAI) and diffuse optical tomography (DOT) into a single
platform for imaging human finger joints with fine structures and associated
optical properties. In PAI, spherical focused transducers were utilized to
collect acoustic signals, and the concept of virtual detector was applied in a
conventional back-projection algorithm to improve the image quality. A finite
element based reconstruction algorithm was employed to quantitatively recover
optical property distribution in the objects for DOT. The phantom results
indicate that PAI has a maximum lateral resolution of 70 um in resolving
structures of targets. DOT was able to recover both optical absorption and
reduced scattering coefficients of targets accurately. To validate the potential
of this system in clinical diagnosis of joint diseases, the distal
interphalangeal (DIP) joints of 4 healthy female volunteers were imaged. We
successfully obtained high-resolution images of the phalanx and the surrounding
soft tissue via PAI, and recovered both optical absorption and reduced scattering
coefficients of phalanx using DOT. The in vivo results suggest that this dual
modality system has the potential for the early diagnosis of joint diseases such
as osteoarthritis (OA) and rheumatoid arthritis (RA). Integrated PAI/DOT imaging
interface (top) and typical reconstruction of structures and associated optical
properties of a female finger joint via PAI and DOT (bottom).
PMID- 26431475
TI - Functional Impact of Collagens on the Activity Directed by the Promoter of the
alpha5 Integrin Subunit Gene in Corneal Epithelial Cells.
AB - PURPOSE: The early step of corneal wound healing is characterized by the massive
production of fibronectin (FN), whose secretion is progressively replaced by
collagens from the basal membrane as wound healing proceeds. Here, we examined
whether expression of the gene encoding the alpha5 subunit from the FN-binding
integrin alpha5beta1 changes as corneal epithelial cells (CECs) are cultured in
the presence of collagen type I (CI) or type IV (CIV). METHODS: Responsiveness of
the alpha5 gene toward collagen was determined by transfection of alpha5
promoter/chloramphenicol acetyltransferase (CAT) plasmids into rabbit and human
CECs cultured on BSA or collagens. Electrophoretic mobility shift assays and
Western blots were used to monitor the transcription factors required for basal
alpha5 gene transcription in the presence of collagens. Gene profiling on
microarrays was used to determine the impact of collagens on the patterns of
genes expressed by CECs. RESULTS: All collagen types repressed the full-length
alpha5/CAT promoter activity in confluent CECs. A moderate increase was observed
in subconfluent rabbit CECs grown on CIV but not on CI. These collagen-dependent
regulatory influences also correlated with alterations in the transcription
factors Sp1/Sp3, NFI, and AP-1 that ensure alpha5 gene basal transcription.
Microarray analyses revealed that CI more profoundly altered the pattern of genes
expressed by human CECs than CIV. CONCLUSIONS: Collagens considerably suppressed
alpha5 gene expression in CECs, suggesting that during wound healing, they may
interfere with the influence FN exerts on CECs by altering their adhesive and
migratory properties through a mechanism involving a reduction in alpha5 gene
expression.
PMID- 26431474
TI - Erp29 Attenuates Cigarette Smoke Extract-Induced Endoplasmic Reticulum Stress and
Mitigates Tight Junction Damage in Retinal Pigment Epithelial Cells.
AB - PURPOSE: Endoplasmic reticulum protein 29 (ERp29) is a novel chaperone that was
recently found decreased in human retinas with AMD. Herein, we examined the
effect of ERp29 on cigarette smoke-induced RPE apoptosis and tight junction
disruption. METHODS: Cultured human RPE (HRPE) cells (ARPE-19) or mouse RPE
eyecup explants were exposed to cigarette smoke extract (CSE) for short (up to 24
hours) or long (up to 3 weeks) periods. Expression of ERp29 was up- and
downregulated by adenovirus and siRNA, respectively. Endoplasmic reticulum stress
markers, apoptosis, and cell death, the expression and distribution of tight
junction protein ZO-1, transepithelial electrical resistance (TEER), and F-actin
expression were examined. RESULTS: Endoplasmic reticulum protein 29 was
significantly increased by short-term exposure to CSE in ARPE-19 cells or eyecup
explants but was reduced after 3-week exposure. Overexpression of ERp29 increased
the levels of GRP78, p58(IPK), and Nrf-2, while reducing p-eIF2alpha and C/EBP
homologous protein (CHOP), and protected RPE cells from CSE-induced apoptosis. In
contrast, knockdown of ERp29 decreased the levels of p58(IPK) and Nrf2, but
increased p-eIF2alpha and CHOP and exacerbated CSE-triggered cell death. In
addition, overexpression of ERp29 attenuated CSE-induced reduction in ZO-1 and
enhanced the RPE barrier function, as measured by TEER. Knockdown of ERp29
decreased the level of ZO-1 protein. These effects were associated with changes
in the expression of cytoskeleton F-actin. CONCLUSIONS: Endoplasmic reticulum
protein 29 attenuates CSE-induced ER stress and enhances cell viability and
barrier integrity of RPE cells, and therefore may act as a protective mechanism
for RPE survival and activity.
PMID- 26431477
TI - Erratum.
PMID- 26431476
TI - The Usefulness of Gaze Tracking as an Index of Visual Field Reliability in
Glaucoma Patients.
AB - PURPOSE: We evaluated the usefulness of gaze tracking (GT) results as an index of
visual field reliability in glaucoma. METHODS: The study population consisted of
631 eyes of 400 patients with open angle glaucoma in an institutional practice,
with 10 visual fields (VFs). For the observational procedure, visual fixation was
assessed using the gaze fixation chart at the bottom of the VF (Humphrey Field
Analyzer, 30-2 SITA standard) printout. Average frequency of eye movement between
1 degrees and 2 degrees (move(1-2)), 3 degrees and 5 degrees (move(3-5)), and
greater than or equal to 6 degrees (move(>=6)) were calculated. In addition,
average tracking failure frequency (TFF) and average blinking frequency (BF) were
calculated. The relationship between mean deviation (MD), fixation losses (FLs),
false-positives (FPs), false-negatives (FNs), move(1-2), move(3-5), move(>=6),
TFF, BF, and pattern standard deviation (PSD) were evaluated using linear
modeling. Main outcome measures included parameters related to over- or
underestimation of MD values. RESULTS: Patients' mean MD progression rate was
0.23 dB/y. The best model to predict MD values included FL rate, FP rate, move(3
5), move(>=6), TFF, BF, and PSD as dependent variables with coefficients of 0.90,
9.2, -0.57, -0.52, -2.2, -1.1, and -0.56, respectively (P < 0.001). CONCLUSIONS:
High FL and FP rates tend to raise MD values. By contrast, high values of move(3
5), move(>=6), TFF, BF, and PSD tend to lower MD values. Thus, GT parameters can
be used as new indices of VF reliability through the prediction of over- or
underestimation of VF results.
PMID- 26431478
TI - Evaluation of the Association Between Common Genetic Variants Near the ABCA1 Gene
and Primary Angle Closure Glaucoma in a Han Chinese Population.
AB - PURPOSE: Recently, three large genome-wide association studies have identified
multiple variants associated with primary open angle glaucoma (POAG) near the
ABCA1 gene. Considering that POAG and primary angle closure glaucoma (PACG) share
many similar clinical manifestations, the present study was conducted to
investigate whether these genetic variants were also associated with PACG in a
Han Chinese population. METHODS: A case-control association study of 1122 cases
(PACG/PAC) and 1311 normal, matched controls was undertaken. Seven single
nucleotide polymorphisms (SNPs) near the ABCA1 gene, including rs2422493,
rs2487042, rs2472496, rs2472493, rs2487032, rs2472459, and rs2472519, were
genotyped. Genotype and allele frequencies were assessed using chi2 tests.
Linkage disequilibrium (LD) structure was analyzed by computer software. RESULTS:
Among the SNPs genotyped, no association was observed between these SNPs and
PACG. However, we discovered that two haplotypes, CATTTAC (corrected P = 0.048)
and CGCCCGC (corrected P = 0.048), remained significantly associated with
PACG/PAC after Bonferroni correction. Subjects with the CATTTAC haplotype have a
1.71-fold increased possibility of having PACG/PAC, whereas subjects with the
CGCCCGC haplotype have 0.47-fold decreased possibility of developing PACG.
CONCLUSIONS: Our findings suggest that the genetic backgrounds of PACG and POAG
might be different. However, whether or not ABCA1 plays a role in the development
of PACG is still not made certain by this study. Thus, further research is needed
to find the role of ABCA1 in the progress of PACG.
PMID- 26431481
TI - Assessment of Visual and Chromatic Functions in a Rodent Model of Retinal
Degeneration.
AB - PURPOSE: We evaluated the photoreceptor response of pigmented P23H and normal
pigmented Long Evans (LE) rats over time using functional tests in variable
lighting conditions. METHODS: Pigmented P23H rats were studied by optomotor
testing and electroretinogram (ERG) recordings at P30, P150, and P240. Pigmented
LE rats were used as a normal wild-type control. Stimuli were modified with
colored filters. Neutral density filters were used to reduce luminance. RESULTS:
Age-related decreases in visual acuity (VA) and contrast sensitivity (CS) were
observed in P23H rats. Good correlations in measurements without filter and with
green filter were observed between LE and P23H P30 rat values. Differences
between groups were smaller with red and purple filters. A strong relationship
with luminance was observed in LE rats (VA and CS) and with P23H P30 rats (CS). A
decline in the ERG responses of P23H rats was consistent with the gradual loss of
photoreceptors. Differences in a- and b-wave amplitudes with different colored
filters were negligible with the exception of the red filter, which resulted in
smaller responses. CONCLUSIONS: Visual function parameters decreased with age in
pigmented P23H rats. Irrespective of luminance, color filter, and retinal
degeneration, minimum thresholds of VA and CS were found. Smaller differences
than expected were found using color filters. Responses to functional tests at
long wavelengths were observed, where there is very low photoreceptor spectral
sensitivity. The use of filters with functional testing could minimize light
induced retinal damage in rats.
PMID- 26431479
TI - Evolutionary Characterization of the Retinitis Pigmentosa GTPase Regulator Gene.
AB - PURPOSE: The evolutionary conservation of the retinitis pigmentosa GTPase
regulator (RPGR) gene was examined across vertebrate and invertebrate lineages to
elucidate its function. METHODS: Orthologous RPGR sequences from vertebrates and
invertebrates were selected. Multiple sequence alignments, phylogenetic analyses,
synteny, and gene structure comparisons were carried out. Expression of the
alternatively spliced constitutive (RPGR(const) or RPGR(ex1-19)) and RPGR(ORF15)
isoforms was examined in developing and adult zebrafish. RESULTS: Phylogenetic
analyses and syntenic relationships were consistent with the selected sequences
being true orthologues, although whole genome duplications in teleost fish
resulted in a more complex picture. The splice form RPGR(const) was present in
all vertebrate and invertebrate species but the defining carboxyl (C)-terminal
exon of RPGR(ORF15) was absent from all invertebrates. The regulator of
chromosome condensation (RCC1)-like domain adopts a seven-bladed beta-propeller
structure, which was present in both major splice forms and strongly conserved
across evolution. The repetitive acidic region of RPGR(ORF15) showed a high rate
of in-frame deletions/insertions across nine primate species, compared with
flanking sequences, consistent with an unstable and rapidly evolving region. In
zebrafish, RPGR(const) transcripts were most strongly expressed in early
development, while the RPGR(ORF15) isoform showed highest expression in adult
eye. CONCLUSIONS: The regulator of chromosome condensation 1-like domain of RPGR
was conserved in vertebrates and invertebrates, but RPGR(ORF15) was unique to
vertebrates, consistent with a proposed role in the ciliary-based transport of
cargoes such as rhodopsin, which is ~10 times more abundant in vertebrate than
invertebrate photoreceptors. The repetitive acidic region of RPGR(ORF15) shows a
rapid rate of evolution, consistent with a mutation "hot spot."
PMID- 26431480
TI - Effects of Cytokine Activation and Oxidative Stress on the Function of the Human
Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells.
AB - PURPOSE: In several retinal complications, such as age-dependent macular
degeneration (AMD), oxidative stress is increased and cytokine level is elevated.
These are shown to alter the activation and expression of matrix
metalloproteinase (MMP) both in human primary and immortalized retinal pigment
epithelial (RPE) cells. However, the effects on human embryonic stem cell (hESC)
derived RPE cells remain to be elucidated. METHODS: The mature hESC-RPE cells
were exposed to inflammatory cytokines (IFN-gamma or TNF-alpha) for 24 hours or
oxidative stress (H2O2) for 1 hour. Effects on barrier properties were analyzed
with transepithelial electrical resistance (TEER), the expression of MMP-1, MMP
2, MMP-3, MMP-9, collagen I, and collagen IV genes with quantitative RT-PCR, and
the expression of MMP-1 and MMP-3 proteins with Western blot or ELISA,
respectively. Also, activation and secretion of MMP-2 and -9 proteins were
analyzed with zymography. RESULTS: In normal state, mature hESC-RPE cells
expressed MMP-1, -2, -3, and -9 genes in low levels, respectively. Tumor necrosis
factor-alpha increased MMP-1 and -2 gene expression, and H2O2 increased MMP-3 and
-9 gene expression. Zymography revealed IFN-gamma- and TNF-alpha-induced
secretion of MMP-2 and high-molecular-weight species of MMP (HMW MMP), but H2O2
decreased their secretion. Furthermore, TNF-alpha and H2O2 significantly
decreased barrier properties. CONCLUSIONS: Here, cytokines induced the MMP-1 and
2 gene and protein expression. Also, H2O2 induced MMP-3 and -9 gene expression,
but not their protein secretion. These data propose that under oxidative stress
and cytokine stimuli, mature hESC-RPE cells resemble their native counterpart in
the human eye in regard to MMP secretion and expression and could be used to
model retinal disorders involving alterations in MMP activity such as AMD,
diabetic retinopathy, or proliferative vitreoretinopathy in vitro.
PMID- 26431482
TI - Combined 60 degrees Wide-Field Choroidal Thickness Maps and High-Definition En
Face Vasculature Visualization Using Swept-Source Megahertz OCT at 1050 nm.
AB - PURPOSE: To demonstrate ultrahigh-speed swept-source optical coherence tomography
(SS-OCT) at 1.68 million A-scans/s for choroidal imaging in normal and diseased
eyes over a ~60 degrees field of view. To investigate and correlate wide-field
three-dimensional (3D) choroidal thickness (ChT) and vascular patterns using ChT
maps and coregistered high-definition en face images extracted from a single
densely sampled Megahertz-OCT (MHz-OCT) dataset. METHODS: High-definition, ~60
degrees wide-field 3D datasets consisting of 2088 * 1024 A-scans were acquired
using a 1.68 MHz prototype SS-OCT system at 1050 nm based on a Fourier-domain
mode-locked laser. Nine subjects (nine eyes) with various chorioretinal diseases
or without ocular pathology are presented. Coregistered ChT maps, choroidal
summation maps, and depth-resolved en face images referenced to either the
retinal pigment epithelium or the choroidal-scleral interface were generated
using manual segmentation. RESULTS: Wide-field ChT maps showed a large inter- and
intraindividual variance in peripheral and central ChT. In only four of the nine
eyes, the location with the largest ChT was coincident with the fovea. The
anatomy of the large lumen vessels of the outer choroid seems to play a major
role in determining the global ChT pattern. Focal ChT changes with large
thickness gradients were observed in some eyes. CONCLUSIONS: Different ChT and
vascular patterns could be visualized over ~60 degrees in patients for the first
time using OCT. Due to focal ChT changes, a high density of thickness
measurements may be favorable. High-definition depth-resolved en face images are
complementary to cross sections and thickness maps and enhance the interpretation
of different ChT patterns.
PMID- 26431484
TI - Increasing Attentional Load Boosts Saccadic Adaptation.
AB - PURPOSE: Visual exploration relies on saccadic eye movements and attention
processes. Saccadic adaptation mechanisms, which calibrate the oculomotor
commands to continuously maintain the accuracy of saccades, have been suggested
to act at downstream (motor) and upstream (visuoattentional) levels of visuomotor
transformation. Conversely, whether attention can directly affect saccadic
adaptation remains unknown. To answer this question, we manipulated the level of
attention engaged in a visual discrimination task performed during saccadic
adaptation. METHODS: Participants performed low or high attention demanding
orientation discrimination tasks on largely or faintly oriented Gabor patches,
respectively, which served as targets for reactive saccades. Gabor patches
systematically jumped backward during eye motion to elicit an adaptive shortening
of saccades, and replaced 50 msec later (100 msec in two subjects) by a mask.
Subjects judged whether Gabors' orientation was "nearly horizontal" versus
"nearly vertical" (low attention demanding) or "slightly left" versus "slightly
right" (high attention demanding), or made no discrimination (control task).
RESULTS: We found that the build-up and the retention of adaptation of reactive
saccades were larger in the "high attention demanding" condition than in the "low
attention demanding" and the no-discrimination control conditions. CONCLUSIONS:
These results indicate that increasing the level of attention to the perceptual
processing of otherwise identical targets boosts saccadic adaptation, and suggest
that saccadic adaptation mechanisms and attentional load effects may functionally
share common neural substrates.
PMID- 26431483
TI - Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod
Dysfunction, and Impaired Visual Performance in Diabetic Mice.
AB - PURPOSE: Diabetes appears to induce a visual cycle defect because rod dysfunction
is correctable with systemic treatment of the visual cycle chromophore 11-cis
retinaldehyde. However, later studies have found no evidence for visual cycle
impairment. Here, we further examined whether photoreceptor dysfunction is
corrected with 11-cis-retinaldehyde. Because antioxidants correct photoreceptor
dysfunction in diabetes, the hypothesis that exogenous visual chromophores have
antioxidant activity in the retina of diabetic mice in vivo was tested. METHODS:
Rod function in 2-month-old diabetic mice was evaluated using transretinal
electrophysiology in excised retinas and apparent diffusion coefficient (ADC) MRI
to measure light-evoked expansion of subretinal space (SRS) in vivo. Optokinetic
tracking was used to evaluate cone-based visual performance. Retinal production
of superoxide free radicals, generated mostly in rod cells, was biochemically
measured with lucigenin. Diabetic mice were systemically treated with a single
injection of either 11-cis-retinaldehyde, 9-cis-retinaldehyde (a chromophore
surrogate), or all-trans-retinaldehyde (the photoisomerization product of 11-cis
retinaldehyde). RESULTS: Consistent with previous reports, diabetes significantly
reduced (1) dark-adapted rod photo responses (transretinal recording) by ~18%,
(2) rod-dominated light-stimulated SRS expansion (ADC MRI) by ~21%, and (3) cone
dominated contrast sensitivity (using optokinetic tracking [OKT]) by ~30%. Both
11-cis-retinaldehyde and 9-cis-retinaldehyde largely corrected these metrics of
photoreceptor dysfunction. Higher-than-normal retinal superoxide production in
diabetes by ~55% was also significantly corrected following treatment with 11-cis
retinaldehyde, 9-cis-retinaldehyde, or all-trans-retinaldehyde. CONCLUSIONS:
Collectively, data suggest that retinaldehydes improve photoreceptor dysfunction
in diabetic mice, independent of the visual cycle, via an antioxidant mechanism.
PMID- 26431486
TI - From WCl6 to WCl2: Properties of Intermediate Fe-W-Cl Phases.
AB - Phenomenological studies of WCl6 reduction with transition metal powders M = Mn,
Fe, and Co have been recently reported. These reactions involve a series of
reductive intercalation steps of M atoms into layered tungsten chloride
arrangements, followed by exsolution of MCl2. In the series M = Fe, the presence
of divalent iron is evidenced for Fe(x)WCl6, FeW2Cl10, Fe2W2Cl10, and (Fe,W)Cl2
by Mossbauer spectroscopy. Magnetic properties are reported. Bonding
characteristics between tungsten atoms in edge-sharing [W2Cl10](n-) bioctahedra
reveal that a double bond can be addressed to FeW2Cl10. A similar situation
appears for Fe2W2Cl10, due to the localized and thus nonbonding character of the
two electrons in the delta orbitals of this compound.
PMID- 26431485
TI - Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis.
AB - PURPOSE: We recently reported that corneal lymphatic vessels develop integrin
alpha-9 (Itga-9)-positive valves during inflammatory lymphangiogenesis. The
purpose of this study was to further investigate the role of Itga-9 in corneal
lymphatic valve formation in vivo and lymphatic endothelial cell (LEC) functions
in vitro. METHODS: Standard murine suture placement model was used to study the
effect of Itga-9 blockade on lymphatic valve formation in vivo using Itga-9
neutralizing antibody. Whole-mount corneas were harvested for immunofluorescent
microscopic analysis. Additionally, human LEC culture system was used to examine
the effect of Itga-9 gene knockdown on cell functions using small interfering
RNAs (siRNAs). RESULTS: Itga-9 blockade in vivo significantly reduced the number
of lymphatic valves formed in the inflamed cornea. Moreover, Itga-9 gene
knockdown in human LECs suppresses cell functions of proliferation, adhesion,
migration, and tube formation. CONCLUSIONS: Itga-9 is critically involved in
corneal lymphatic valve formation. Further investigation of the Itga-9 pathway
may provide novel strategies to treat lymphatic-related diseases occurring both
inside and outside the eye.
PMID- 26431487
TI - Creative Self-Efficacy: An Exploration of Its Antecedents, Consequences, and
Applied Implications.
AB - Creativity and innovation are at the core of important outcomes such as economic
and sales growth, production of articles and students' learning. Thus, it is not
surprising to find research articles on creativity and innovation across
different disciplines such as business, psychology, and education. Given the
importance of understanding creativity and innovation, we reviewed the empirical
literature examining the antecedents and consequences of creative self-efficacy
in the work domain. Our review used the theory of individual creative action and
social cognitive theory as guiding frameworks to place creative self-efficacy in
the creativity and innovation process, define creativity and innovation, explore
how creative self-efficacy has been measured, examine the antecedents and
consequences of creative self-efficacy, point out gaps in knowledge and offer
suggestions for future research and provide some applied implications. One
important finding was that creative self-efficacy has made a significant
contribution as a process variable explaining how several organizational and
personal factors influence creative outcomes via their influence on creative self
efficacy.
PMID- 26431488
TI - Metagenomic Human Repiratory Air in a Hospital Environment.
AB - Hospital-acquired infection (HAI) or nosocomial infection is an issue that
frequent hospital environment. We believe conventional regulated Petri dish
method is insufficient to evaluate HAI. To address this problem, metagenomic
sequencing was applied to screen airborne microbes in four rooms of Beijing
Hospital. With air-in amount of sampler being setup to one person's respiration
quantity, metagenomic sequencing identified huge numbers of species in the rooms
which had already qualified widely accepted petridish exposing standard, imposing
urgency for new technology. Meanwhile,the comparative culture only got small
portion of recovered species and remain blind for even cultivable pathogens
reminded us the limitations of old technologies. To the best of our knowledge,
the method demonstrated in this study could be broadly applied in hospital indoor
environment for various monitoring activities as well as HAI study. It is also
potential as a transmissible pathogen real-time modelling system worldwide.
PMID- 26431489
TI - Identification of thyroid tumor cell vulnerabilities through a siRNA-based
functional screening.
AB - The incidence of thyroid carcinoma is rapidly increasing. Although generally
associated with good prognosis, a fraction of thyroid tumors are not cured by
standard therapy and progress to aggressive forms for which no effective
treatments are currently available. In order to identify novel therapeutic
targets for thyroid carcinoma, we focused on the discovery of genes essential for
sustaining the oncogenic phenotype of thyroid tumor cells, but not required to
the same degree for the viability of normal cells (non-oncogene addiction
paradigm). We screened a siRNA oligonucleotide library targeting the human
druggable genome in thyroid cancer BCPAP cell line in comparison with
immortalized normal human thyrocytes (Nthy-ori 3-1). We identified a panel of hit
genes whose silencing interferes with the growth of tumor cells, while sparing
that of normal ones. Further analysis of three selected hit genes, namely Cyclin
D1, MASTL and COPZ1, showed that they represent common vulnerabilities for
thyroid tumor cells, as their inhibition reduced the viability of several thyroid
tumor cell lines, regardless the histotype or oncogenic lesion. This work
identified non-oncogenes essential for sustaining the phenotype of thyroid tumor
cells, but not of normal cells, thus suggesting that they might represent
promising targets for new therapeutic strategies.
PMID- 26431491
TI - Long non-coding RNA profiling links subgroup classification of endometrioid
endometrial carcinomas with trithorax and polycomb complex aberrations.
AB - BACKGROUND: Integrative analysis of endometrioid endometrial carcinoma (EEC)
using multiple platforms has distinguished four molecular subgroups. However, the
landscape of expressed long non-coding RNAs (lncRNA) and their role in charting
EEC subgroups and determining clinical aggressiveness remain largely unknown.
RESULTS: Using stringent criteria, we identified 1,931 expressed lncRNAs and
predicted potential drivers through integrative analysis. Unsupervised clustering
of lncRNA expression revealed three robust categories: basal-like, luminal-like
and CTNNB1-enriched subgroups. Basal-like subgroup was enriched for aggressive
tumors with higher pathological grade (p < 0.0001), TNM stage (p = 0.01), and
somatic mutations in trithorax-group genes (MLL, MLL2 and MLL3); and it
overexpressed polycomb genes EZH2 and CBX2. In contrast to the luminal-like
subgroup, progesterone (PGR) and estrogen receptor (ESR1) genes were highly down
regulated in the EEC basal-like subgroup. Consistent with its enrichment for
CTNNB1 mutations (69%), lncRNA profile of the CTNNB1-enriched EEC subgroup was
highly similar to that of the CTNNB1-enriched liver cancer subgroup. MATERIALS
AND METHODS: We performed integrative analysis of lncRNAs in EEC using The Cancer
Genome Atlas (TCGA) molecular RNAseq profiles of 191 primary tumors for which
genomic data were also available. We established lncRNA subgroup classification,
correlated it with chromatin modifying gene expression, and described
correlations between our lncRNA classification and clinico-genomic tumor
features. CONCLUSIONS: Our results reveal the utility of systematic
characterization of clinically annotated EEC in three clinically relevant
subgroups. They also highlight the convergence of aberrations in polycomb- and
trithorax-group genes in aggressive basal EEC subtypes, providing a rationale for
further investigation of epigenetic therapy in this setting.
PMID- 26431490
TI - Nodal metastasis in cervical cancer occurs in clearly delineated fields of immune
suppression in the pelvic lymph catchment area.
AB - In cervical cancer, high frequencies of regulatory T cells (Tregs) and
immunosuppressive PD-L1+CD14+ antigen-presenting cells dominate the
microenvironment of tumor-positive lymph nodes (LN+). It is unknown whether this
is restricted to LN+ or precedes metastasis, emanating from the primary tumor and
spreading through tumor-draining lymph nodes (TDLNs). To investigate
immunosuppression in the lymphatic basin of cervical tumors, all dissected TDLNs
of five cervical cancer patients (in total 9 LN+ and 74 tumor-negative lymph
nodes (LN-)) were analyzed for FoxP3+ Tregs, CD8+ T cells, HLA-DR+- and PD-L1+
myeloid cells by immunohistochemistry.Tregs and PD-L1+ cells were found to form
an immunosuppressive cordon around metastatic tumor cells. Importantly, whereas
high HLA-DR+- and PD-L1+ cell rates were strongly associated with LN+, elevated
Treg levels and decreased CD8+ T cell/Treg ratios were found similar in LN+ and
adjacent LN-, as compared to LN- at more distant anatomical localizations. These
data suggest that delineated fields of Treg-associated immune suppression in
anatomically co-localized TDLNs enable metastasis by creating metastatic niches.
This may be of importance for decision-making regarding (surgical) intervention
in cervical cancer. Future efforts should include the implementation of
immunotherapeutic regimens to overcome this immune suppression, establish loco
regional control and halt systemic tumor spread.
PMID- 26431492
TI - Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial
cells during chronic inflammation and colitis-associated cancer by regulating
S100A9.
AB - Many host-factors are inducibly expressed during the development of inflammatory
bowel disease (IBD), each having their unique properties, such as immune
activation, bacterial clearance, and tissue repair/remodeling.
Dysregulation/imbalance of these factors may have pathogenic effects that can
contribute to colitis-associated cancer (CAC). Previous reports showed that IBD
patients inducibly express colonic chitinase 3-like 1 (CHI3L1) that is further
upregulated during CAC development. However, little is known about the direct
pathogenic involvement of CHI3L1 in vivo. Here we demonstrate that CHI3L1 (aka
Brp39) knockout (KO) mice treated with azoxymethane (AOM)/dextran sulphate sodium
(DSS) developed severe colitis but lesser incidence of CAC as compared to that in
wild-type (WT) mice. Highest CHI3L1 expression was found during the chronic phase
of colitis, rather than the acute phase, and is essential to promote intestinal
epithelial cell (IEC) proliferation in vivo. This CHI3L1-mediated cell
proliferation/survival involves partial downregulation of the pro-apoptotic
S100A9 protein that is highly expressed during the acute phase of colitis, by
binding to the S100A9 receptor, RAGE (Receptor for Advanced Glycation End
products). This interaction disrupts the S100A9-associated expression positive
feedback loop during early immune activation, creating a CHI3L1hi S100A9low
colonic environment, especially in the later phase of colitis, which promotes
cell proliferation/survival of both normal IECs and tumor cells.
PMID- 26431494
TI - Association of FGFR3 and FGFR4 gene polymorphisms with breast cancer in Chinese
women of Heilongjiang province.
AB - BACKGROUND: The fibroblast growth factor (FGF) receptor pathway is activated in
many tumors. FGFR2 has been identified as a breast cancer susceptibility gene.
Common variation in other FGF receptors might also affect breast cancer risk. We
carried out a case-control study to investigate associations of variants in FGFR3
and FGFR4 with breast cancer in women from Heilongjiang Province. METHODS: SNP
rs2234909 and rs3135848 in FGFR3 and rs1966265 and rs351855 in FGFR4 were
successfully genotyped in 747 breast cancer patients and 716 healthy controls
using the SNaPshot method. The associations between SNPs and breast cancer were
examined by logistic regression. The associations between SNPs and disease
characteristics were examined by chi-square tests or one-way ANOVA as needed.
RESULTS: The minor alleles of rs1966265 and rs351855 in FGFR4 were strongly
associated with breast cancer in the population, with odds ratios of 1.335 (95%CI
= 1.154-1.545) and 1.364 (95%CI = 1.177-1.580), respectively. However, no
significant associations were detected between other SNPs and breast cancer.
Analyses of the disease characteristics showed that SNP rs351855 was associated
with lymph-node-positive breast cancer with a dose-dependent effect of the minor
allele (P = 0.008). CONCLUSIONS: SNPs rs1966265 and rs351855 in FGFR4 were
associated with breast cancer in a northern Chinese population.
PMID- 26431496
TI - ENT1 and treatment of viral diseases.
PMID- 26431497
TI - Undoing SUMO aids polyQ AR.
PMID- 26431493
TI - The molecular effect of metastasis suppressors on Src signaling and
tumorigenesis: new therapeutic targets.
AB - A major problem for cancer patients is the metastasis of cancer cells from the
primary tumor. This involves: (1) migration through the basement membrane; (2)
dissemination via the circulatory system; and (3) invasion into a secondary site.
Metastasis suppressors, by definition, inhibit metastasis at any step of the
metastatic cascade. Notably, Src is a non-receptor, cytoplasmic, tyrosine kinase,
which becomes aberrantly activated in many cancer-types following stimulation of
plasma membrane receptors (e.g., receptor tyrosine kinases and integrins). There
is evidence of a prominent role of Src in tumor progression-related events such
as the epithelial-mesenchymal transition (EMT) and the development of metastasis.
However, the precise molecular interactions of Src with metastasis suppressors
remain unclear. Herein, we review known metastasis suppressors and summarize
recent advances in understanding the mechanisms of how these proteins inhibit
metastasis through modulation of Src. Particular emphasis is bestowed on the
potent metastasis suppressor, N-myc downstream regulated gene 1 (NDRG1) and its
interactions with the Src signaling cascade. Recent studies demonstrated a novel
mechanism through which NDRG1 plays a significant role in regulating cancer cell
migration by inhibiting Src activity. Moreover, we discuss the rationale for
targeting metastasis suppressor genes as a sound therapeutic modality, and we
review several examples from the literature where such strategies show promise.
Collectively, this review summarizes the essential interactions of metastasis
suppressors with Src and their effects on progression of cancer metastasis.
Moreover, interesting unresolved issues regarding these proteins as well as their
potential as therapeutic targets are also discussed.
PMID- 26431495
TI - What links BRAF to the heart function? New insights from the cardiotoxicity of
BRAF inhibitors in cancer treatment.
AB - The RAS-related signalling cascade has a fundamental role in cell. It activates
differentiation and survival. It is particularly important one of its molecules,
B-RAF. B-RAF has been a central point for research, especially in melanoma.
Indeed, it lacked effective therapeutic weapons since the early years of its
study. Molecules targeting B-RAF have been developed. Nowadays, two classes of
molecules are approved by FDA. Multi-target molecules, such as Sorafenib and
Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many
other molecules are still under investigation. Most of them are studied in phase
1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though
this cardiovascular side effect is not common using these drugs, it must be
noticed early and recognize its signals. Indeed, Oncologists and Cardiologists
should work in cooperation to prevent lethal events, such as fatal arrhythmias or
sudden cardiac death. These events could originate from an uncontrolled QT
prolongation.
PMID- 26431499
TI - Self-Assembly of Ferritin Nanoparticles into an Enzyme Nanocomposite with Tunable
Size for Ultrasensitive Immunoassay.
AB - The self-assembly of nanoparticles into larger superstructures is a powerful
strategy to develop novel functional nanomaterials, as these superstructures
display collective properties that are different to those displayed by individual
nanoparticles or bulk samples. However, there are increasing bottlenecks in terms
of size control and multifunctionalization of nanoparticle assemblies. In this
study, we developed a self-assembly strategy for construction of multifunctional
nanoparticle assemblies of tunable size, through rational regulation of the
number of self-assembling interaction sites on each nanoparticle. As proof-of
principle, a size-controlled enzyme nanocomposite (ENC) was constructed by self
assembly of streptavidin-labeled horseradish peroxidase (SA-HRP) and
autobiotinylated ferritin nanoparticles (bFNP). Our ENC integrates a large number
of enzyme molecules, together with a streptavidin-coated surface, allowing for a
drastic increase in enzymatic signal when the SA is bound to a biotinylated
target molecule. As result, a 10 000-fold increase in sensitivity over
conventional enzyme-linked immunosorbent assays (ELISA) methods was achieved in a
cardiac troponin immunoassay. Our method presented here should provide a feasible
approach for constructing elaborate multifunctional superstructures of tunable
size useful for a broad range of biomedical applications.
PMID- 26431498
TI - Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer
experimental bone metastasis in mouse models.
AB - Bone metastasis is a frequent occurrence in prostate cancer patients and often is
lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited
efficacy. More effective models and treatment methods are required to improve the
outcome of prostate cancer patients. In the present study, the effects of tumor
targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on
prostate cancer cells and experimental bone metastasis. Both ZOL and S.
typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent
protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate
cancer experimental bone metastasis, we established models of both early and
advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1
R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S.
typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium
A1-R treatment significantly decreased bone metastasis and delayed the appearance
of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1
R treatment significantly improved the overall survival of the mice with multiple
bone metastases. The results of the present study indicate that S. typhimurium A1
R is useful to prevent and inhibit prostate cancer bone metastasis and has
potential for future clinical use in the adjuvant setting.
PMID- 26431506
TI - Cognitive Performance at Late Adolescence and the Risk for Impaired Fasting
Glucose Among Young Adults.
AB - CONTEXT: Although dysglycemia is a risk factor for cognitive decline, it is
unknown whether cognitive performance among young and apparently healthy adults
affect the risk for impaired fasting glucose (IFG). OBJECTIVE: This study aimed
to characterize the relationship between cognitive function and the risk for IFG
among young adults. DESIGN AND SETTING: This was a retrospective cohort study
utilizing data collected at pre-military recruitment assessments with information
collected at the screening center of Israeli Army Medical Corps. PARTICIPANTS:
Normoglycemic adults (n = 17 348) (free of IFG and diabetes; mean age 31.0 +/-
5.6 y; 87% men) of the Metabolic Lifestyle and Nutrition Assessment in Young
Adults (MELANY) cohort with data regarding their General Intelligence Score
(GIS), a comprehensive measure of cognitive function, at age 17 y. INTERVENTIONS:
Fasting plasma glucose was assessed every 3-5 y at scheduled visits. Cox
proportional hazards models were applied. MAIN OUTCOMES MEASURES: The main
outcome of the study was incident IFG (>= 100 mg/dL and <126 mg/dL) at scheduled
visits. RESULTS: During a median followup of 6.6 y, 1478 cases of IFG were
recorded (1402 men). After adjustment for age and sex, participants in the lowest
GIS category had a 1.9-fold greater risk for incident IFG compared with those in
the highest GIS category. In multivariable analysis adjusted for age, sex, body
mass index, fasting plasma glucose, family history of diabetes, country of
origin, socioeconomic status, education, physical activity, smoking status,
alcohol consumption, breakfast consumption, triglyceride level, white blood cell
count, the risk for IFG was nearly doubled in the lowest GIS category compared
with the highest GIS category (hazard ratio, 1.8; 95% confidence interval, 1.4
2.3; P < .001). These results persisted when GIS was treated as a continuous
variable and when the model was adjusted also for body mass index at the end of
followup. CONCLUSIONS: This study demonstrates that lower cognitive function at
late adolescence is independently associated with an elevated risk IFG in both
men and women.
PMID- 26431507
TI - Genetic Predisposition to Polycystic Ovary Syndrome, Postpartum Weight Reduction,
and Glycemic Changes: A Longitudinal Study in Women With Prior Gestational
Diabetes.
AB - CONTEXT: Polycystic ovary syndrome (PCOS) is a common condition in reproductive
aged women and a major female-specific risk factor of obesity, impaired glucose
tolerance, and diabetes. OBJECTIVE: We examined whether the genetic variation
predisposing to PCOS affected glycemic changes in women with prior gestational
diabetes mellitus (GDM) and whether such an effect was modified by changes in
body adiposity, especially during and after pregnancy. DESIGN, SETTING, AND
PARTICIPANTS: This is a longitudinal study in Tianjin, China. We genotyped 7
genome-wide association study-identified PCOS single nucleotide polymorphisms and
assessed gestational weight gain and changes in glycemic traits and weight at 1
to 5 years postpartum in 1133 women with prior GDM. MAIN OUTCOME MEASURES: The
main outcome measure was postpartum glycemic changes. RESULTS: The PCOS genetic
risk score significantly interacted with postpartum weight reduction on changes
in fasting glucose and 2-h glucose (P for interaction = .032 and .007;
respectively) after multivariable adjustment. In women with postpartum weight
reduction of >= 5 kg/y, the genetic risk score was associated with decreased
fasting and 2-h glucose, whereas an opposite genetic effect was found in women
who lost less weight. The association between postpartum weight reduction and
glycemic improvement was more significant among women with a higher genetic risk
score. CONCLUSIONS: In a large cohort of Chinese women with a history of GDM, our
data for the first time indicate that the genetic predisposition to PCOS may
interact with postpartum weight reduction on long-term glycemic changes,
emphasizing the importance of postpartum weight management in prevention of
diabetes in this subgroup of women.
PMID- 26431508
TI - Low Frequency of Cardiomyopathy Using Cardiac Magnetic Resonance Imaging in an
Acromegaly Contemporary Cohort.
AB - CONTEXT: Left ventricular hypertrophy (LVH) and myocardial fibrosis are
considered common findings of the acromegaly cardiomyopathy in echocardiography
studies. OBJECTIVE: To evaluate the frequency of LVH, systolic dysfunction and
myocardial fibrosis was undertaken in patients with acromegaly using cardiac
magnetic resonance imaging (CMRi) before and after 12 months of octreotide long
acting repeatable treatment. PATIENTS AND METHODS: Consecutive patients with
active acromegaly submitted to biochemical analysis and CMRi before and after 12
months of treatment. Additionally, echocardiography was performed before
treatment. RESULTS: Forty consecutive patients were evaluated using CMRi at
baseline and 30 patients were reevaluated after 12 months of treatment.
Additionally, 29 of these patients were submitted to echocardiography. Using
CMRi, the frequency of LVH was 5%. The mean left ventricular mass index (LVMi)
was 61.73 +/- 18.8 g/m(2). The mean left ventricular ejection fraction (LVEF) was
61.85 +/- 9.2%, and all patients had normal systolic function. Late gadolinium
enhancement was present in five patients (13.5%), and one patient (3.5%) had an
increased extracellular volume. After treatment, 12 patients (40%) had criteria
for disease control. No clinically relevant differences in cardiac variables
before and after treatment were observed. Additionally, there was no difference
in LVMi and LVEF among patients with and without disease control. Using
echocardiography, 31% of the patients had LVH, mean LVMi was 117.8 +/- 46.3
g/m(2) and mean LVEF was 67.3 +/- 4.4%. All patients had normal systolic
function. CONCLUSIONS: We demonstrated by CMRi, the gold-standard method, that
patients with active acromegaly might have a lower prevalence of cardiac
abnormalities than previously reported.
PMID- 26431509
TI - High Incidence of Heterozygous ABCC8 and HNF1A Mutations in Czech Patients With
Congenital Hyperinsulinism.
AB - CONTEXT: Congenital hyperinsulinism of infancy (CHI) represents a group of
heterogeneous disorders characterized by oversecretion of insulin from pancreatic
beta-cells causing severe hypoglycemia. OBJECTIVE: We studied the distribution of
genetic causes of CHI in a Czech population. METHODS: Countrywide collection of
patients with CHI included 40 subjects (12 females, median age of diagnosis, 1 wk
[interquartile range, 1-612 wk]). We sequenced the ABCC8, KCNJ11, GLUD1, GCK,
HADH, UCP2, SLC16A1, HNF4A, and HNF1A genes and investigated structural changes
in the ABCC8 gene. We functionally tested novel variants in the ABCC8 gene by
Rb(86+) efflux assay and novel variants in the HNF1A gene by transcriptional
activation and DNA-binding tests. RESULTS: We found causal mutations in 20
subjects (50%): 19 carried a heterozygous mutation while one patient was
homozygous for mutation in the ABCC8 gene. Specifically, we detected 11 mutations
(seven novel) in ABCC8, one novel mutation in KCNJ11, five mutations (two novel)
in HNF1A, two novel mutations in HNF4A, and one in GCK. We showed a decrease of
activation by diazoxide in mutant KATP channels with novel ABCC8 variants by 41
91% (median, 82%) compared with wild-type (WT) channels and reduced
transcriptional activity of mutant HNF1A proteins (2.9% for p.Asn62Lysfs93* and
22% for p.Leu254Gln) accompanied by no DNA-binding ability compared with WT
HNF1A. CONCLUSION: We detected a higher proportion of heterozygous mutations
causing CHI compared with other cohorts probably due to lack of consanguinity and
inclusion of milder CHI forms. Interestingly, HNF1A gene mutations represented
the second most frequent genetic cause of CHI in the Czech Republic. Based on our
results we present a genetic testing strategy specific for similar populations.
PMID- 26431510
TI - Malnutrition in Hospitals: It Was, Is Now, and Must Not Remain a Problem!
AB - BACKGROUND: Malnutrition is an under-recognized problem in hospitalized patients.
Despite systematic screening, the prevalence of malnutrition in the hospital did
not decrease in the last few decades. The aim of our study was to evaluate the
prevalence of malnutrition and to determine the explicit daily calorie intake of
hospitalized patients, to identify the risk factors of developing malnutrition
during hospitalization and the effect on the financial reimbursement according to
the German DRG-system. MATERIAL AND METHODS: 815 hospitalized patients were
included in this study. The detection of malnutrition was based on the
nutritional-risk-screening (NRS) and subjective-global-assessment (SGA) scores. A
trained investigator recorded the daily calorie and fluid intake of each patient.
Furthermore, clinical parameters, and the financial reimbursement were evaluated.
RESULTS: The prevalence of malnutrition was 53.6% according to the SGA and 44.6%
according the NRS. During hospitalization, patients received on average 759.9+/
546.8 kcal/day. The prevalence of malnutrition was increased in patients with
hepatic and gastrointestinal disease and with depression or dementia. The most
important risk factors for malnutrition were bed rest and immobility (OR=5.88,
95% CI 2.25-15.4). In 84.5% of patient records, malnutrition was not correctly
coded, leading to increased financial losses according to the DRG-system (94.908
Euros). CONCLUSIONS: Hospitalized patients suffer from inadequate nutritional
therapy and the risk for developing malnutrition rises during the hospital stay.
The early screening of patients for malnutrition would not only improve
management of nutritional therapy but also, with adequate coding, improve
financial reimbursement according to the DRG-system.
PMID- 26431512
TI - Improving Rural Health Through Support for Academic Progression.
PMID- 26431511
TI - Validation of a Malay Version of the Smartphone Addiction Scale among Medical
Students in Malaysia.
AB - INTRODUCTION: This study was initiated to determine the psychometric properties
of the Smart Phone Addiction Scale (SAS) by translating and validating this scale
into the Malay language (SAS-M), which is the main language spoken in Malaysia.
This study can distinguish smart phone and internet addiction among multi-ethnic
Malaysian medical students. In addition, the reliability and validity of the SAS
was also demonstrated. MATERIALS AND METHODS: A total of 228 participants were
selected between August 2014 and September 2014 to complete a set of
questionnaires, including the SAS and the modified Kimberly Young Internet
addiction test (IAT) in the Malay language. RESULTS: There were 99 males and 129
females with ages ranging from 19 to 22 years old (21.7+/-1.1) included in this
study. Descriptive and factor analyses, intra-class coefficients, t-tests and
correlation analyses were conducted to verify the reliability and validity of the
SAS. Bartlett's test of sphericity was significant (p <0.01), and the Kaiser
Mayer-Olkin measure of sampling adequacy for the SAS-M was 0.92, indicating
meritoriously that the factor analysis was appropriate. The internal consistency
and concurrent validity of the SAS-M were verified (Cronbach's alpha = 0.94). All
of the subscales of the SAS-M, except for positive anticipation, were
significantly related to the Malay version of the IAT. CONCLUSIONS: This study
developed the first smart phone addiction scale among medical students. This
scale was shown to be reliable and valid in the Malay language.
PMID- 26431513
TI - Qualitative Analysis of Student Perceptions of Bachelor of Science-to-Doctor of
Philosophy in Nursing Programs.
AB - BACKGROUND: To address the shortage of Doctor of Philosophy (PhD)-prepared
nursing faculty, universities in the United States offer direct-entry Bachelor of
Science in Nursing (BSN)-to-PhD nursing programs. Little research has been
conducted to explore students' perceptions of these programs and to formally
evaluate the successes and opportunities for growth of this academic track.
METHOD: Focusing on the perceptions and experiential reflection of BSN-to-PhD
education, a survey with open-ended questions was distributed among voluntary
participants who are current BSN-to-PhD students or recent graduates (within 5
years) from various universities in the United States. Textual data were analyzed
using a qualitative descriptive approach with thematic analysis. RESULTS: This
article elaborates on opportunities, challenges, and suggestions related to this
educational route, as recognized by 21 participants from seven universities.
CONCLUSION: The study findings may facilitate discussion among nurse educators to
revise programs to be congruent with the needs of current students while paving
the way for future scholars.
PMID- 26431514
TI - Development and Psychometric Assessment of the Nursing Competence Self-Efficacy
Scale.
AB - BACKGROUND: The study aim was to develop and psychometrically assess an
instrument to measure baccalaureate nursing students' self-efficacy for practice
competence. Social cognitive theory includes the construct of self-efficacy and
supports this study. METHOD: Before the Nursing Competence Self-Efficacy Scale
(NCSES) was administered to senior nursing students (N = 252), nursing experts in
research, practice, instrument development, and psychometrics participated in a
two-step validation process consisting of two reviews. Construct validity
assessments included content, face, contrasting groups, criterion, and
exploratory factor analysis (EFA). The chosen EFA solution consisted of 22 items,
each moderately or highly loaded by one of four factors deemed to be
interpretable and parsimonious. RESULTS: The initial psychometric assessment of
the NCSES supported construct validity, internal consistency reliability (.919),
and test-retest stability reliability (r = .831). CONCLUSION: With further
psychometric assessment, the NCSES can be useful to evaluate new curriculum
interventions aimed at increasing students' self-efficacy for comprehensive
practice competence.
PMID- 26431515
TI - Role of Self-Directed Learning in Communication Competence and Self-Efficacy.
AB - BACKGROUND: Although effective self-directed learning (SDL) has been shown to
improve clinical performance, little is known about its role between
communication competence and communication self-efficacy in nursing students.
This study aimed to identify whether SDL mediates the relationship between
communication competence and communication self-efficacy. METHOD: A cross
sectional survey was conducted with a sample of 213 nursing students taking a
basic fundamentals of nursing course. A path diagram, using structural equation
modeling, was used to estimate the direct and indirect effects of communication
competence on communication self-efficacy, controlling for SDL as a mediator.
RESULTS: A structural equation model confirmed direct and indirect effects of
communication competence on communication self-efficacy when SDL was controlled
as a mediator. An appropriate fit to the data was identified in this mediation
model of SDL. CONCLUSIONS: For enhancing self-efficacy regarding communication
skill, the specified SDL program based on the level of communication competence
will yield more effective results.
PMID- 26431516
TI - Bibliometric Patterns of Research Literature Production on Nursing Informatics
Competence.
AB - BACKGROUND: Nursing informatics competence is a prerequisite for successful
information management, evidence-based practices optimizing patient care health
promotion, and communication with information communication technology-literate
patients. METHOD: The aim of this study was to assess the trends in the
production of nursing informatics competence research literature and to identify
the most productive bibliometric entities. In addition to the correspondence
analysis, bibliometric analysis and mapping were used to achieve the aim.
RESULTS: A total of 366 information sources were extracted, 14.5% of which were
sponsored studies. The production of research literature on nursing informatics
competence is growing, but this research is only occasionally published in the
most recognized nursing journals. CONCLUSION: Identifying where the intensive
research on nursing informatics competence is beneficial to care for the patient
of the future and building user-friendly online lifelong learning platforms,
where a required level of nursing informatics competence could be acquired, are
two gaps in the current research that should be covered in future.
PMID- 26431517
TI - A Systematic Review of the Experience of Using Second Life in the Education of
Undergraduate Nurses.
AB - BACKGROUND: The virtual world of Second Life((r)) is an emerging technology that
is being considered as a simulation methodology for the education of
professionals. Particularly for nursing, the adoption of simulation, although a
response to technological advancement, is occurring during changes in population
health care needs, the resultant impact on the workforce, and also the changing
profile of students. METHOD: This systematic review aimed to establish the
current applications of Second Life in the education of undergraduate nursing
students. Databases searched were CINAHL((r)), Medline((r)), Education Research
Complete(TM), ERIC(TM), Computers and Applied Sciences Complete(TM), and Library,
Information Sciences and Technology(TM). RESULTS: Fourteen studies met the
inclusion and exclusion criteria. Evidence identified included the themes of
transferability from theory to practice, focus on learner centeredness, and
evaluative processes. CONCLUSION: This review demonstrates that positive learning
outcomes are achievable in Second Life. Evaluative research is in an early stage,
and further investigation is warranted.
PMID- 26431518
TI - Using Debates to Teach Evidence-Based Practice in Large Online Courses.
AB - BACKGROUND: To engage in evidence-based practice (EBP), baccalaureate nursing
graduates' competencies must include locating, interpreting, appraising, and
applying research findings. Faculty are challenged to find effective ways to
incorporate this content in large online courses. METHOD: Faculty in a thriving
college of nursing used interactive debates to teach EBP skills in a large (200+
students) online undergraduate course. RESULTS: Students remain highly engaged
while practicing critical thinking, team-work, leadership, delegation,
communication skills, and peer evaluation through participation in a series of
faculty-facilitated online debates. CONCLUSION: Meticulous course organization
and use of structured debates allows one instructor to teach skills for EBP,
while keeping students engaged with each other, the instructor, and the material.
Use of debates and the amount of engagement among students and faculty achieved
could not be accomplished in a large face-to-face course.
PMID- 26431519
TI - Can Learning the ISBARR Framework Help to Address Nursing Students' Perceived
Anxiety and Confidence Levels Associated With Handover Reports?
AB - BACKGROUND: Standardized communication frameworks are believed to help students
feel more confident and less anxious about handover reports. One of the handover
communication frameworks being used in nursing programs was the ISBARR framework
(Identify, Situation, Background, Assessment, Recommendation, and Repeat). The
aim was to explore whether learning the ISBARR framework affected nursing
students' perceived anxiety and confidence levels associated with handover
reports. METHOD: The study tested null hypotheses by analyzing pre- and posttest
data collected with the Competitive State Anxiety Inventory-2 (CSAI-2) survey.
Three qualitative questions were included in the posttest to compare with the
quantitative data. Statistical significance was set at p = .02. RESULTS: The
results revealed that learning the framework had a strong effect in reducing the
perceived somatic anxiety levels, a medium effect on increasing perceived
confidence levels, and a medium effect in reducing the perceived cognitive
anxiety levels. CONCLUSION: Findings suggested that learning the standardized
framework may help to address students' perceived anxiety and confidence levels
associated with handover reports and generate a mental picture of handover
reports.
PMID- 26431520
TI - Using Simulation Pedagogy in the Formation of Family-Focused Generalist Nurses.
AB - BACKGROUND: Nursing practice with families is essential because a family member's
illness affects the family and, reciprocally, the family influences health
outcomes. Yet, nurses often report a lack of confidence in their ability to meet
the needs of families, whereas family members often describe troubling
experiences with nurses. These challenges may have beginning roots in nursing
education. This article explores the use of simulation in the formation of family
focused generalist nurses. METHOD: Simulation pedagogy was used to guide students
in developing an understanding of the importance of family nursing care, gaining
confidence in family practices, and developing family competencies. RESULTS:
Innovative simulation learning experiences in an undergraduate nursing curriculum
helped students to learn how to develop nurse-family relationships and gain
humanistic skills of family nursing practices. Students and faculty reported that
simulation guides students to achieve meaningful outcomes. CONCLUSION: In this
curriculum, faculty consistently directs attention to the family in simulation
learning experiences, and students value this pedagogy.
PMID- 26431522
TI - Adapting a Social Media Strategy in the Classroom: PEET.
PMID- 26431521
TI - Evolving the PICOT Method for the Digital Age: The PICOT-D.
AB - BACKGROUND: Many articles written about the PICOT (Population, Intervention,
Comparison, Outcome, Time) method for developing research questions focus on
searching the existing evidence base to review the impact of interventions. The
PICOT method evolved to craft questions that yield operative search terms.
Currently, the PICOT method falls short in its utility for health care and
doctoral education. For example, the Doctor of Nursing Practice scholarly
practice projects evaluate the existing evidence base and compare the current
real-world state with the evidence base, for which the current conceptualization
of the PICOT method has limited applicability. METHOD: The PICOT-D adds digital
data (D) components to the traditional PICOT, allowing for the explicit
identification of data measures that form the basis of the evaluation of an
intervention. RESULTS: the PICOT-D has the potential to improve student
efficiency, efficacy, and confidence in the development of truly answerable
questions that fully support improved patient care and systems-level change.
CONCLUSION: This article demonstrates the need for the evolution of the PICOT
format to the PICOT-D format.
PMID- 26431524
TI - Correction: Evaluation of Commercial Diagnostic Assays for the Specific Detection
of Avian Influenza A (H7N9) Virus RNA Using a Quality-Control Panel and Clinical
Specimens in China.
PMID- 26431523
TI - A New Method for Detecting Associations with Rare Copy-Number Variants.
AB - Copy number variants (CNVs) play an important role in the etiology of many
diseases such as cancers and psychiatric disorders. Due to a modest marginal
effect size or the rarity of the CNVs, collapsing rare CNVs together and
collectively evaluating their effect serves as a key approach to evaluating the
collective effect of rare CNVs on disease risk. While a plethora of powerful
collapsing methods are available for sequence variants (e.g., SNPs) in
association analysis, these methods cannot be directly applied to rare CNVs due
to the CNV-specific challenges, i.e., the multi-faceted nature of CNV
polymorphisms (e.g., CNVs vary in size, type, dosage, and details of gene
disruption), and etiological heterogeneity (e.g., heterogeneous effects of
duplications and deletions that occur within a locus or in different loci).
Existing CNV collapsing analysis methods (a.k.a. the burden test) tend to have
suboptimal performance due to the fact that these methods often ignore
heterogeneity and evaluate only the marginal effects of a CNV feature. We
introduce CCRET, a random effects test for collapsing rare CNVs when searching
for disease associations. CCRET is applicable to variants measured on a multi
categorical scale, collectively modeling the effects of multiple CNV features,
and is robust to etiological heterogeneity. Multiple confounders can be
simultaneously corrected. To evaluate the performance of CCRET, we conducted
extensive simulations and analyzed large-scale schizophrenia datasets. We show
that CCRET has powerful and robust performance under multiple types of
etiological heterogeneity, and has performance comparable to or better than
existing methods when there is no heterogeneity.
PMID- 26431525
TI - Effects of Prism Eyeglasses on Objective and Subjective Fixation Disparity.
AB - In optometry of binocular vision, the question may arise whether prisms should be
included in eyeglasses to compensate an oculomotor and/or sensory imbalance
between the two eyes. The corresponding measures of objective and subjective
fixation disparity may be reduced by the prisms, or the adaptability of the
binocular vergence system may diminish effects of the prisms over time. This
study investigates effects of wearing prisms constantly for about 5 weeks in
daily life. Two groups of 12 participants received eyeglasses with prisms having
either a base-in direction or a base-out direction with an amount up to 8 prism
diopters. Prisms were prescribed based on clinical fixation disparity test plates
at 6 m. Two dependent variables were used: (1) subjective fixation disparity was
indicated by a perceived offset of dichoptic nonius lines that were superimposed
on the fusion stimuli and (2) objective fixation disparity was measured with a
video based eye tracker relative to monocular calibration. Stimuli were presented
at 6 m and included either central or more peripheral fusion stimuli. Repeated
measurements were made without the prisms and with the prisms after about 5 weeks
of wearing these prisms. Objective and subjective fixation disparity were
correlated, but the type of fusion stimulus and the direction of the required
prism may play a role. The prisms did not reduce the fixation disparity to zero,
but induced significant changes in fixation disparity with large effect sizes.
Participants receiving base-out prisms showed hypothesized effects, which were
concurrent in both types of fixation disparity. In participants receiving base-in
prisms, the individual effects of subjective and objective effects were
negatively correlated: the larger the subjective (sensory) effect, the smaller
the objective (motor) effect. This response pattern was related to the vergence
adaptability, i.e. the individual fusional vergence reserves.
PMID- 26431526
TI - Phylogenesis and Biological Characterization of a New Glucose Transporter in the
Chicken (Gallus gallus), GLUT12.
AB - In mammals, insulin-sensitive GLUTs, including GLUT4, are recruited to the plasma
membrane of adipose and muscle tissues in response to insulin. The GLUT4 gene is
absent from the chicken genome, and no functional insulin-sensitive GLUTs have
been characterized in chicken tissues to date. A nucleotide sequence is predicted
to encode a chicken GLUT12 ortholog and, interestingly, GLUT12 has been described
to act as an insulin-sensitive GLUT in mammals. It encodes a 596 amino acid
protein exhibiting 71% identity with human GLUT12. First, we present the results
of a phylogenetic study showing the stability of this gene during evolution of
vertebrates. Second, tissue distribution of chicken SLC2A12 mRNA was
characterized by RT-PCR. It was predominantly expressed in skeletal muscle and
heart. Protein distribution was analysed by Western blotting using an anti-human
GLUT12 antibody directed against a highly conserved region (87% of identity). An
immuno-reactive band of the expected size (75kDa) was detected in the same
tissues. Third a physiological characterization was performed: SLC2A12 mRNA
levels were significantly lowered in fed chickens subjected to insulin immuno
neutralization. Finally, recruitment of immuno-reactive GLUT12 to the muscle
plasma membrane was increased following 1h of intraperitoneal insulin
administration (compared to a control fasted state). Thus insulin administration
elicited membrane GLUT12 recruitment. In conclusion, these results suggest that
the facilitative glucose transporter protein GLUT12 could act in chicken muscle
as an insulin-sensitive transporter that is qualitatively similar to GLUT4 in
mammals.
PMID- 26431527
TI - Using Mathematical Modelling to Explore Hypotheses about the Role of Bovine
Epithelium Structure in Foot-And-Mouth Disease Virus-Induced Cell Lysis.
AB - Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed
animals. FMD virus (FMDV) shows a strong tropism for epithelial cells, and FMD is
characterised by cell lysis and the development of vesicular lesions in certain
epithelial tissues (for example, the tongue). By contrast, other epithelial
tissues do not develop lesions, despite being sites of viral replication (for
example, the dorsal soft palate). The reasons for this difference are poorly
understood, but hypotheses are difficult to test experimentally. In order to
identify the factors which drive cell lysis, and consequently determine the
development of lesions, we developed a partial differential equation model of
FMDV infection in bovine epithelial tissues and used it to explore a range of
hypotheses about epithelium structure which could be driving differences in lytic
behaviour observed in different tissues. Our results demonstrate that, based on
current parameter estimates, epithelial tissue thickness and cell layer structure
are unlikely to be determinants of FMDV-induced cell lysis. However, differences
in receptor distribution or viral replication amongst cell layers could influence
the development of lesions, but only if viral replication rates are much lower
than current estimates.
PMID- 26431528
TI - Influence of Factors of Cryopreservation and Hypothermic Storage on Survival and
Functional Parameters of Multipotent Stromal Cells of Placental Origin.
AB - Human placenta is a highly perspective source of multipotent stromal cells (MSCs)
both for the purposes of patient specific auto-banking and allogeneic application
in regenerative medicine. Implementation of new GMP standards into clinical
practice enforces the search for relevant methods of cryopreservation and short
term hypothermic storage of placental MSCs. In this paper we analyze the effect
of different temperature regimes and individual components of cryoprotective
media on viability, metabolic and culture properties of placental MSCs. We
demonstrate (I) the possibility of short-term hypothermic storage of these cells;
(II) determine DMSO and propanediol as the most appropriate cryoprotective
agents; (III) show the possibility of application of volume expanders (plasma
substituting solutions based on dextran or polyvinylpyrrolidone); (IV) reveal the
priority of ionic composition over the serum content in cryopreservation media;
(V) determine a cooling rate of 1 degrees C/min down to -40 degrees C followed by
immersion into liquid nitrogen as the optimal cryopreservation regime for this
type of cells. This study demonstrates perspectives for creation of new defined
cryopreservation methods towards GMP standards.
PMID- 26431530
TI - A Putative PP2C-Encoding Gene Negatively Regulates ABA Signaling in Populus
euphratica.
AB - A PP2C homolog gene was cloned from the drought-treated cDNA library of Populus
euphratica. Multiple sequence alignment analysis suggested that the gene is a
potential ortholog of HAB1. The expression of this HAB1 ortholog (PeHAB1) was
markedly induced by drought and moderately induced by ABA. To characterize its
function in ABA signaling, we generated transgenic Arabidopsis thaliana plants
overexpressing this gene. Transgenic lines exhibited reduced responses to
exogenous ABA and reduced tolerance to drought compared to wide-type lines. Yeast
two-hybrid analyses indicated that PeHAB1 could interact with the ABA receptor
PYL4 in an ABA-independent manner. Taken together; these results indicated that
PeHAB1 is a new negative regulator of ABA responses in poplar.
PMID- 26431529
TI - The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS)
Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic
Reperfusion Injury.
AB - Although repetitive Transcranial Magnetic Stimulation (rTMS) in treatment of
stroke in humans has been explored over the past decade the data remain
controversial in terms of optimal stimulation parameters and the mechanisms of
rTMS long-term effects. This study aimed to explore the potential of different
rTMS protocols to induce changes in gene expression in rat cortices after acute
ischemic-reperfusion brain injury. The stroke was induced by middle cerebral
artery occlusion (MCAO) with subsequent reperfusion. Changes in the expression of
96 genes were examined using low-density expression arrays after MCAO alone and
after MCAO combined with 1Hz, 5Hz, continuous (cTBS) and intermittent (iTBS)
theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with
a 2-day pause) in a single daily session and a total of 2400 pulses. MCAO alone
induced significant upregulation in the expression of 44 genes and downregulation
in 10. Two weeks of iTBS induced significant increase in the expression of 52
genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects
on gene expression, while cTBS effects were negligible. Upregulated genes
included those involved in angiogenesis, inflammation, injury response and
cellular repair, structural remodeling, neuroprotection, neurotransmission and
neuronal plasticity. The results show that long-term rTMS in acute ischemic
reperfusion brain injury induces complex changes in gene expression that span
multiple pathways, which generally promote the recovery. They also demonstrate
that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs.
iTBS) and pattern (cTBS vs. iTBS). The results further underlines the premise
that one of the benefits of rTMS application in stroke may be to prime the brain,
enhancing its potential to cope with the injury and to rewire. This could further
augment its potential to favorably respond to rehabilitation, and to restore some
of the loss functions.
PMID- 26431531
TI - The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors
of Lung Adenocarcinoma.
AB - Synthetic lethality arises when a combination of mutations in two or more genes
leads to cell death. However, the prognostic role of concordant overexpression of
synthetic lethality genes in protein level rather than a combination of mutations
is not clear. In this study, we explore the prognostic role of combined
overexpression of paired genes in lung adenocarcinoma. We used
immunohistochemical staining to investigate 24 paired genes in 93 lung
adenocarcinoma patients and Kaplan-Meier analysis and Cox proportional hazards
models to evaluate their prognostic roles. Among 24 paired genes, only FEN1 (Flap
endonuclease 1) and RAD54B (RAD54 homolog B) were overexpressed in lung
adenocarcinoma patients with poor prognosis. Patients with expression of both
FEN1 and RAD54B were prone to have advanced nodal involvement and significantly
poor prognosis (HR = 2.35, P = 0.0230). These results suggest that intensive
follow up and targeted therapy might improve clinical outcome for patients who
show expression of both FEN1 and RAD54B.
PMID- 26431532
TI - The Small Molecule DAM Inhibitor, Pyrimidinedione, Disrupts Streptococcus
pneumoniae Biofilm Growth In Vitro.
AB - Streptococcus pneumoniae persist in the human nasopharynx within organized
biofilms. However, expansion to other tissues may cause severe infections such as
pneumonia, otitis media, bacteremia, and meningitis, especially in children and
the elderly. Bacteria within biofilms possess increased tolerance to antibiotics
and are able to resist host defense systems. Bacteria within biofilms exhibit
different physiology, metabolism, and gene expression profiles than planktonic
cells. These differences underscore the need to identify alternative therapeutic
targets and novel antimicrobial compounds that are effective against pneumococcal
biofilms. In bacteria, DNA adenine methyltransferase (Dam) alters pathogenic gene
expression and catalyzes the methylation of adenine in the DNA duplex and of
macromolecules during the activated methyl cycle (AMC). In pneumococci, AMC is
involved in the biosynthesis of quorum sensing molecules that regulate competence
and biofilm formation. In this study, we examine the effect of a small molecule
Dam inhibitor, pyrimidinedione, on Streptococcus pneumoniae biofilm formation and
evaluate the changes in global gene expression within biofilms via microarray
analysis. The effects of pyrimidinedione on in vitro biofilms were studied using
a static microtiter plate assay, and the architecture of the biofilms was viewed
using confocal and scanning electron microscopy. The cytotoxicity of
pyrimidinedione was tested on a human middle ear epithelium cell line by CCK-8.
In situ oligonucleotide microarray was used to compare the global gene expression
of Streptococcus pneumoniae D39 within biofilms grown in the presence and absence
of pyrimidinedione. Real-time RT-PCR was used to study gene expression.
Pyrimidinedione inhibits pneumococcal biofilm growth in vitro in a concentration
dependent manner, but it does not inhibit planktonic cell growth. Confocal
microscopy analysis revealed the absence of organized biofilms, where cell-clumps
were scattered and attached to the bottom of the plate when cells were grown in
the presence of pyrimidinedione. Scanning electron microscopy analysis
demonstrated the absence of an extracellular polysaccharide matrix in
pyrimidinedione-grown biofilms compared to control-biofilms. Pyrimidinedione also
significantly inhibited MRSA, MSSA, and Staphylococcus epidermidis biofilm growth
in vitro. Furthermore, pyrimidinedione does not exhibit eukaryotic cell toxicity.
In a microarray analysis, 56 genes were significantly up-regulated and 204 genes
were significantly down-regulated. Genes involved in galactose metabolism were
exclusively up-regulated in pyrimidinedione-grown biofilms. Genes related to DNA
replication, cell division and the cell cycle, pathogenesis, phosphate-specific
transport, signal transduction, fatty acid biosynthesis, protein folding,
homeostasis, competence, and biofilm formation were down regulated in
pyrimidinedione-grown biofilms. This study demonstrated that the small molecule
Dam inhibitor, pyrimidinedione, inhibits pneumococcal biofilm growth in vitro at
concentrations that do not inhibit planktonic cell growth and down regulates
important metabolic-, virulence-, competence-, and biofilm-related genes. The
identification of a small molecule (pyrimidinedione) with S. pneumoniae biofilm
inhibiting capabilities has potential for the development of new compounds that
prevent biofilm formation.
PMID- 26431533
TI - The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell
Responses.
AB - Memory CD8 T cells provide protection to immune hosts by eliminating pathogen
infected cells during re-infection. While parameters influencing the generation
of primary (1 degrees ) CD8 T cells are well established, the factors controlling
the development of secondary (2 degrees ) CD8 T cell responses remain largely
unknown. Here, we address the mechanisms involved in the generation and
development of 2 degrees memory (M) CD8 T cells. We observed that the time at
which 1 degrees M CD8 T cells enter into immune response impacts their fate and
differentiation into 2 degrees M CD8 T cells. Late-entry of 1 degrees M CD8 T
cells into an immune response (relative to the onset of infection) not only
facilitated the expression of transcription factors associated with memory
formation in 2 degrees effector CD8 T cells, but also influenced the ability of
2 degrees M CD8 T cells to localize within the lymph nodes, produce IL-2, and
undergo Ag-driven proliferation. The timing of stimulation of 1 degrees M CD8 T
cells also impacted the duration of expression of the high-affinity IL-2 receptor
(CD25) on 2 degrees effector CD8 T cells and their sensitivity to IL-2
signaling. Importantly, by blocking or enhancing IL-2 signaling in developing 2
degrees CD8 T cells, we provide direct evidence for the role of IL-2 in
controlling the differentiation of Ag-driven 2 degrees CD8 T cell responses.
Thus, our data suggest that the process of 1 degrees M to 2 degrees M CD8 T
cell differentiation is not fixed and can be manipulated, a notion with relevance
for the design of future prime-boost vaccination approaches.
PMID- 26431534
TI - Enhanced Activation of Canonical Wnt Signaling Confers Mesoderm-Derived Parietal
Bone with Similar Osteogenic and Skeletal Healing Capacity to Neural Crest
Derived Frontal Bone.
AB - Bone formation and skeletal repair are dynamic processes involving a fine-tuned
balance between osteoblast proliferation and differentiation orchestrated by
multiple signaling pathways. Canonical Wnt (cWnt) signaling is known to playing a
key role in these processes. In the current study, using a transgenic mouse model
with targeted disruption of axin2, a negative regulator of cWnt signaling, we
investigated the impact of enhanced activation of cWnt signaling on the
osteogenic capacity and skeletal repair. Specifically, we looked at two calvarial
bones of different embryonic tissue origin: the neural crest-derived frontal bone
and the mesoderm-derived parietal bone, and we investigated the proliferation and
apoptotic activity of frontal and parietal bones and derived osteoblasts. We
found dramatic differences in cell proliferation and apoptotic activity between
Axin2-/- and wild type calvarial bones, with Axin2-/- showing increased
proliferative activity and reduced levels of apoptosis. Furthermore, we compared
osteoblast differentiation and bone regeneration in Axin2-/- and wild type neural
crest-derived frontal and mesoderm-derived parietal bones, respectively. Our
results demonstrate a significant increase either in osteoblast differentiation
or bone regeneration in Axin2-/- mice as compared to wild type, with Axin2-/-
parietal bone and derived osteoblasts displaying a "neural crest-derived frontal
bone-like" profile, which is typically characterized by higher osteogenic
capacity and skeletal repair than parietal bone. Taken together, our results
strongly suggest that enhanced activation of cWnt signaling increases the
skeletal potential of a calvarial bone of mesoderm origin, such as the parietial
bone to a degree similar to that of a neural crest origin bone, like the frontal
bone. Thus, providing further evidence for the central role played by the cWnt
signaling in osteogenesis and skeletal-bone regeneration.
PMID- 26431535
TI - Newly Isolated Penicillium ramulosum N1 Is Excellent for Producing Protease
Resistant Acidophilic Xylanase.
AB - Penicillium ramulosum N1 was isolated from decaying wood. This strain produces
extracellular xylanases and cellulases. The highest activities of xylanases (250
U/ml) and carboxymethyl cellulose (CMCase; 6.5 U/ml) were produced when 1% barley
straw was added as a carbon source. The optimum temperature and pH for xylanase
activity was 55 and 3.0 degrees C, respectively. The xylanases exhibited strong
protease resistance. CMCase revealed maximum activities at pH 3.0 and in the
range of 60-70 degrees C. Filter paper activity was optimally active at pH 5.0
and 55 degrees C. The zymograms produced by the SDS-PAGE resolution of the crude
enzymes indicated that there are four bands of protein with xylanase activity and
three bands of proteins with endoglucanase. The results revealed that P.
ramulosum N1 is a promising acidophilic and protease-resistant xylanase-producing
microorganism that has great potential to be used in animal feed and food
industry applications.
PMID- 26431536
TI - How Possibly Do Leisure and Social Activities Impact Mental Health of Middle-Aged
Adults in Japan?: An Evidence from a National Longitudinal Survey.
AB - OBJECTIVES: This study aimed to investigate longitudinal relations between
leisure and social activities and mental health status, considering the presence
or absence of other persons in the activity as an additional variable, among
middle-aged adults in Japan. This study used nationally representative data in
Japan with a five-year follow-up period. METHODS: This study focused on 16,642
middle-aged adults, age 50-59 at baseline, from a population-based, six-year
panel survey conducted by the Japanese Ministry of Health, Labour and Welfare. To
investigate the relations between two leisure activities ('hobbies or cultural
activities' and 'exercise or sports') and four social activities ('community
events', 'support for children', 'support for elderly individuals' and 'other
social activities') at baseline and mental health status at follow-up, multiple
logistic regression analysis was used. We also used multiple logistic regression
analysis to investigate the association between ways of participating in these
activities ('by oneself', 'with others', or 'both' (both 'by oneself' and 'with
others')) at baseline and mental health status at follow-up. RESULTS: Involvement
in both leisure activity categories, but not in social activities, was
significantly and positively related to mental health status in both men and
women. Furthermore, in men, both 'hobbies or cultural activities' and 'exercise
or sports' were significantly related to mental health status only when conducted
'with others'. In women, the effects of 'hobbies or cultural activities' on
mental health status were no differences regardless of the ways of participating,
while the result of 'exercise or sports' was same as that in men. CONCLUSIONS:
Leisure activities appear to benefit mental health status among this age group,
whereas specific social activities do not. Moreover, participation in leisure
activities would be effective especially if others are present. These findings
should be useful for preventing the deterioration of mental health status in
middle-aged adults in Japan.
PMID- 26431537
TI - Trypanosoma cruzi and Its Soluble Antigens Induce NET Release by Stimulating Toll
Like Receptors.
AB - Neutrophils release fibrous traps of DNA, histones, and granule proteins known as
neutrophil extracellular traps (NETs), which contribute to microbicidal killing
and have been implicated in autoimmunity. The role of NET formation in the host
response to nonbacterial pathogens is not well-understood. In this study, we
investigated the release of NETs by human neutrophils upon their interaction with
Trypanosoma cruzi (Y strain) parasites. Our results showed that human neutrophils
stimulated by T. cruzi generate NETs composed of DNA, histones, and elastase. The
release occurred in a dose-, time-, and reactive oxygen species-dependent manner
to decrease trypomastigote and increase amastigote numbers of the parasites
without affecting their viability. NET release was decreased upon blocking with
antibodies against Toll-like receptors 2 and 4. In addition, living parasites
were not mandatory in the release of NETs induced by T. cruzi, as the same
results were obtained when molecules from its soluble extract were tested. Our
results increase the understanding of the stimulation of NETs by parasites,
particularly T. cruzi. We suggest that contact of T. cruzi with NETs during
Chagas's disease can limit infection by affecting the infectivity/pathogenicity
of the parasite.
PMID- 26431538
TI - Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic
Cell Subsets in Oropharyngeal Candidiasis.
AB - Candida spp. can cause severe and chronic mucocutaneous and systemic infections
in immunocompromised individuals. Protection from mucocutaneous candidiasis
depends on T helper cells, in particular those secreting IL-17. The events
regulating T cell activation and differentiation toward effector fates in
response to fungal invasion in different tissues are poorly understood. Here we
generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous
antigen that is conserved in multiple distant species of Candida, including the
clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T
cells in combination with an experimental model of oropharyngeal candidiasis
(OPC) we investigated antigen presentation and Th17 priming by different subsets
of dendritic cells (DCs) present in the infected oral mucosa. Candida-derived
endogenous antigen accesses the draining lymph nodes and is directly presented by
migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte
derived DCs collaborate in antigen presentation and T cell priming during OPC. In
contrast, Langerhans cells, which are also present in the oral mucosa and have
been shown to prime Th17 cells in the skin, are not required for induction of the
Candida-specific T cell response upon oral challenge. This highlights the
functional compartmentalization of specific DC subsets in different tissues.
These data provide important new insights to our understanding of tissue-specific
antifungal immunity.
PMID- 26431539
TI - Endocytosis-Mediated Invasion and Pathogenicity of Streptococcus agalactiae in
Rat Cardiomyocyte (H9C2).
AB - Streptococcus agalactiae infection causes high mortality in cardiovascular
disease (CVD) patients, especially in case of setting prosthetic valve during
cardiac surgery. However, the pathogenesis mechanism of S. agalactiae associate
with CVD has not been well studied. Here, we have demonstrated the pathogenicity
of S. agalactiae in rat cardiomyocytes (H9C2). Interestingly, both live and dead
cells of S. agalactiae were uptaken by H9C2 cells. To further dissect the process
of S. agalactiae internalization, we chemically inhibited discrete parts of
cellular uptake system in H9C2 cells using genistein, chlorpromazine, nocodazole
and cytochalasin B. Chemical inhibition of microtubule and actin formation by
nocodazole and cytochalasin B impaired S. agalactiae internalization into H9C2
cells. Consistently, reverse- transcription PCR (RT-PCR) and quantitative real
time-PCR (RT-qPCR) analyses also detected higher levels of transcripts for
cytoskeleton forming genes, Acta1 and Tubb5 in S. agalactiae-infected H9C2 cells,
suggesting the requirement of functional cytoskeleton in pathogenesis. Host
survival assay demonstrated that S. agalactiae internalization induced
cytotoxicity in H9C2 cells. S. agalactiae cells grown with benzyl penicillin
reduced its ability to internalize and induce cytotoxicity in H9C2 cells, which
could be attributed with the removal of surface lipoteichoic acid (LTA) from S.
agalactiae. Further, the LTA extracted from S. agalactiae also exhibited dose
dependent cytotoxicity in H9C2 cells. Taken together, our data suggest that S.
agalactiae cells internalized H9C2 cells through energy-dependent endocytic
processes and the LTA of S. agalactiae play major role in host cell
internalization and cytotoxicity induction.
PMID- 26431540
TI - Clinical Significance of Mycobacterium kansasii Isolates from Respiratory
Specimens.
AB - The clinical significance of Mycobacterium kansasii respiratory isolates is
uncertain. The aims of this study were to determine the clinical relevance of M.
kansasii isolates and to identify the clinical features and outcomes of M.
kansasii lung disease. We reviewed the medical records of 104 patients from whom
at least one respiratory M. kansasii isolate was obtained from January 2003 to
July 2014 at Samsung Medical Center, South Korea. Of these 104 patients, 54 (52%)
met the diagnostic criteria for nontuberculous mycobacterial lung disease; among
them, 41 (76%) patients received antibiotic treatment for a median time of 15.0
months (interquartile range [IQR], 7.0-18.0 months). The remaining 13 (24%)
without overt disease progression were observed for a median period of 24.0
months (IQR, 5.0-34.5 months). Patients with M. kansasii lung disease exhibited
various radiographic findings of lung disease, including the fibrocavitary form
(n = 24, 44%), the nodular bronchiectatic form (n = 17, 32%), and an
unclassifiable form (n = 13, 24%). The fibrocavitary form was more common in
patients who received treatment (n = 23, 56%), while the nodular bronchiectatic
form was more common in patients with M. kansasii lung disease who did not
receive treatment (n = 9, 70%). None of the patients with a single sputum isolate
(n = 18) developed M. kansasii disease over a median follow-up period of 12.0
months (IQR, 4.0-26.5 months). In total, 52% of all patients with M. kansasii
respiratory isolates exhibited clinically significant disease. Moreover, patients
with M. kansasii lung disease displayed diverse radiographic findings in addition
to the fibrocavitary form. The nodular bronchiectatic form was more common in
patients with M. kansasii lung disease with an indolent clinical course. Thus,
since the clinical significance of a single M. kansasii respiratory isolate is
not definite, strict adherence to recommended diagnostic criteria is advised.
PMID- 26431544
TI - Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus.
AB - BACKGROUND/AIMS: Macrophages have recently been shown to play a critical role in
the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying
mechanisms remain unclear. METHODS: Here, we used an activated lymphocyte-derived
DNA (ALD-DNA) method to induce SLE in mice. We used a macrophage-specific
eliminator clodronate to selectively deplete macrophages in mice. We isolated
macrophages from bone marrow of the mice and used cytokines to differentiate M1
and M2 macrophages, respectively. Adoptive transplantation of M1 or M2
macrophages was performed in clodronate-treated mice. The effects on SLE were
evaluated by serum anti-dsDNA autoantibody, by renal pathological changes, and by
urine protein levels. RESULTS: ALD-DNA induced SLE-like features in mice,
manifested by induction of serum anti-dsDNA autoantibody, by renal pathological
changes, and by increases in urine protein levels. Clodronate significantly
decreased macrophages in mice, which significantly increased SLE severity.
Adoptive transplantation of M2, but not M1 macrophages significantly reduced SLE
severity in clodronate- and ALD-DNA-treated mice. CONCLUSION: M1 and M2
macrophages play different roles in development of SLE. M1 macrophages increase
the severity of SLE, while M2 macrophages reduce it. Modulation of macrophage
polarity may be an attractive therapy for SLE.
PMID- 26431545
TI - The Experience of Chinese Couples Undergoing In Vitro Fertilization Treatment:
Perception of the Treatment Process and Partner Support.
AB - BACKGROUND: Couples undergoing In Vitro Fertilization (IVF) Treatment suffer as
dyads from the stressful experience of the painful treatment and the fear that
the IVF cycle will fail. They are likely to report that their marital
relationship has become unstable due to the prolonged period of treatment.
METHODS: This is a qualitative study that was conducted to explore the
experiences that Chinese couples have had with IVF treatment, especially their
perceptions of the process and the support between couples. RESULTS: The
interviews revealed that couples suffered from the process, experiencing physical
and emotional pain, struggling with the urgency and inflexibility of bearing a
child, and experiencing disturbances in their daily routines and work. The
participants described how they endured the hardships as a couple and how it
affected their relationship. The couples felt that sharing feelings and
supporting each other contribute to psychological well-being and improves the
marital relationship. They also identified some unfavorable aspects in their
partner relationship. They were ambivalent about receiving social support from
friends and family members. CONCLUSIONS: With the couples indicating that the
support that they received from each other affected their experience during the
treatment process, it is suggested that a supportive intervention that focuses on
enhancing the partnership of the couples and dealing with their inflexibility on
the issue of bearing a child might result in improvements in the psychological
status and marital relationship of infertile couples undergoing IVF treatment.
PMID- 26431546
TI - Spatial Distribution of Sand Fly Vectors and Eco-Epidemiology of Cutaneous
Leishmaniasis Transmission in Colombia.
AB - BACKGROUND: Leishmania is transmitted by Phlebotominae insects that maintain the
enzootic cycle by circulating between sylvatic and domestic mammals; humans enter
the cycles as accidental hosts due to the vector's search for blood source. In
Colombia, leishmaniasis is an endemic disease and 95% of all cases are cutaneous
(CL), these cases have been reported in several regions of the country where the
intervention of sylvatic areas by the introduction of agriculture seem to have an
impact on the rearrangement of new transmission cycles. Our study aimed to update
vector species distribution in the country and to analyze the relationship
between vectors' distribution, climate, land use and CL prevalence. METHODS: A
database with geographic information was assembled, and ecological niche modeling
was performed to explore the potential distribution of each of the 21 species of
medical importance in Colombia, using thirteen bioclimatic variables, three
topographic and three principal components derived from NDVI. Binary models for
each species were obtained and related to both land use coverage, and a CL
prevalence map with available epidemiological data. Finally, maps of species
potential distribution were summed to define potential species richness in the
country. RESULTS: In total, 673 single records were obtained with Lutzomyia
gomezi, Lutzomyia longipalpis, Psychodopygus panamensis, Psathyromyia shannoni
and Pintomyia evansi the species with the highest number of records. Eighteen
species had significant models, considering the area under the curve and the
jackknife results: L. gomezi and P. panamensis had the widest potential
distribution. All sand fly species except for Nyssomyia antunesi are mainly
distributed in regions with rates of prevalence between 0.33 to 101.35 cases per
100,000 inhabitants and 76% of collection data points fall into transformed
ecosystems. DISCUSSION: Distribution ranges of sand flies with medical importance
in Colombia correspond predominantly to disturbed areas, where the original land
coverage is missing therefore increasing the domiciliation potential. We
highlight the importance of the use of distribution maps as a tool for the
development of strategies for prevention and control of diseases.
PMID- 26431547
TI - De Novo Transcriptome Assembly and Comparative Analysis Elucidate Complicated
Mechanism Regulating Astragalus chrysochlorus Response to Selenium Stimuli.
AB - Astragalus species are medicinal plants that are used in the world for years.
Some Astragalus species are known for selenium accumulation and tolerance and one
of them is Astragalus chrysochlorus, a secondary selenium accumulator. In this
study, we employed Illumina deep sequencing technology for the first time to de
novo assemble A. chrysochlorus transcriptome and identify the differentially
expressed genes after selenate treatment. Totally, 59,656 unigenes were annotated
with different databases and 53,960 unigenes were detected in NR database.
Transcriptome in A. chrysochlorus is closer to Glycine max than other plant
species with 43,1 percentage of similarity. Annotated unigenes were also used for
gene ontology enrichment and pathway enrichment analysis. The most significant
genes and pathways were ABC transporters, plant pathogen interaction,
biosynthesis of secondary metabolites and carbohydrate metabolism. Our results
will help to enlighten the selenium accumulation and tolerance mechanisms,
respectively in plants.
PMID- 26431549
TI - Isolation and characterization of novel RECK tumor suppressor gene splice
variants.
AB - Glioblastoma multiforme is the most common and lethal of the central nervous
system glial-derived tumors. RECK suppresses tumor invasion by negatively
regulating at least three members of the matrix metalloproteinase family: MMP-9,
MMP-2, and MT1-MMP. A positive correlation has been observed between the
abundance of RECK expression in tumor samples and a more favorable prognosis for
patients with several types of tumors. In the present study, novel alternatively
spliced variants of the RECK gene: RECK-B and RECK-I were isolated by RT-PCR and
sequenced. The expression levels and profiles of these alternative RECK
transcripts, as well as canonical RECK were determined in tissue samples of
malignant astrocytomas of different grades and in a normal tissue RNA panel by
qRT-PCR. Our results show that higher canonical RECK expression, accompanied by a
higher canonical to alternative transcript expression ratio, positively
correlates with higher overall survival rate after chemotherapeutic treatment of
GBM patients. U87MG and T98G cells over-expressing the RECK-B alternative variant
display higher anchorage-independent clonal growth and do not display modulation
of, respectively, MMP-2 and MMP-9 expression. Our findings suggest that RECK
transcript variants might have opposite roles in GBM biology and the ratio of
their expression levels may be informative for the prognostic outcome of GBM
patients.
PMID- 26431550
TI - mTOR Activation by PI3K/Akt and ERK Signaling in Short ELF-EMF Exposed Human
Keratinocytes.
AB - Several reports suggest that ELF-EMF exposures interact with biological processes
including promotion of cell proliferation. However, the molecular mechanisms by
which ELF-EMF controls cell growth are not completely understood. The present
study aimed to investigate the effect of ELF-EMF on keratinocytes proliferation
and molecular mechanisms involved. Effect of ELF-EMF (50 Hz, 1 mT) on HaCaT cell
cycle and cells growth and viability was monitored by FACS analysis and BrdU
assay. Gene expression profile by microarray and qRT-PCR validation was performed
in HaCaT cells exposed or not to ELF-EMF. mTOR, Akt and MAPKs expressions were
evaluated by Western blot analysis. In HaCaT cells, short ELF-EMF exposure
modulates distinct patterns of gene expression involved in cell proliferation and
in the cell cycle. mTOR activation resulted the main molecular target of ELF-EMF
on HaCaT cells. Our data showed the increase of the canonical pathway of mTOR
regulation (PI3K/Akt) and activation of ERK signaling pathways. Our results
indicate that ELF-EMF selectively modulated the expression of multiple genes
related to pivotal biological processes and functions that play a key role in
physio-pathological mechanisms such as wound healing.
PMID- 26431552
TI - ENDOCRINOLOGY OF PREGNANCY: Gestational diabetes mellitus: definition,
aetiological and clinical aspects.
AB - Gestational diabetes (GDM) is defined as a glucose intolerance resulting in
hyperglycaemia of variable severity with onset during pregnancy. This review aims
to revisit the pathogenesis and aetiology of GDM in order to better understand
its clinical presentation and outcomes. During normal pregnancy, insulin
sensitivity declines with advancing gestation. These modifications are due to
placental factors, progesterone and estrogen. In a physiological situation, a
compensatory increase in insulin secretion maintains a normal glucose
homeostasis. GDM occurs if pancreatic beta-cells are unable to face the increased
insulin demand during pregnancy. GDM is most commonly a forerunner of type 2
diabetes (T2D) - the most prevalent form of diabetes. These women share similar
characteristics with predisposed subjects to T2D: insulin resistance before and
after pregnancy, and carry more T2D risk alleles. Auto-immune and monogenic
diabetes are more rare aetiologies of GDM. Adverse pregnancy outcomes of GDM are
mainly related to macrosomia caused by fetal hyperinsulinism in response to high
glucose levels coming from maternal hyperglycaemia. Screening recommendations and
diagnosis criteria of GDM have been recently updated. High risk patients should
be screened as early as possible using fasting plasma glucose, and if normal, at
24-28 weeks of gestation using 75 g oral glucose tolerance test. The treatment of
GDM is based on education with trained nurses and dieticians, and if necessary
insulin therapy.
PMID- 26431551
TI - Definitive Characterization of CA 19-9 in Resectable Pancreatic Cancer Using a
Reference Set of Serum and Plasma Specimens.
AB - The validation of candidate biomarkers often is hampered by the lack of a
reliable means of assessing and comparing performance. We present here a
reference set of serum and plasma samples to facilitate the validation of
biomarkers for resectable pancreatic cancer. The reference set includes a large
cohort of stage I-II pancreatic cancer patients, recruited from 5 different
institutions, and relevant control groups. We characterized the performance of
the current best serological biomarker for pancreatic cancer, CA 19-9, using
plasma samples from the reference set to provide a benchmark for future biomarker
studies and to further our knowledge of CA 19-9 in early-stage pancreatic cancer
and the control groups. CA 19-9 distinguished pancreatic cancers from the healthy
and chronic pancreatitis groups with an average sensitivity and specificity of 70
74%, similar to previous studies using all stages of pancreatic cancer. Chronic
pancreatitis patients did not show CA 19-9 elevations, but patients with benign
biliary obstruction had elevations nearly as high as the cancer patients. We
gained additional information about the biomarker by comparing two distinct
assays. The two CA 9-9 assays agreed well in overall performance but diverged in
measurements of individual samples, potentially due to subtle differences in
antibody specificity as revealed by glycan array analysis. Thus, the reference
set promises be a valuable resource for biomarker validation and comparison, and
the CA 19-9 data presented here will be useful for benchmarking and for exploring
relationships to CA 19-9.
PMID- 26431553
TI - Mutations in the maternally imprinted gene MKRN3 are common in familial central
precocious puberty.
AB - CONTEXT AND OBJECTIVE: Idiopathic central precocious puberty (iCPP) is defined as
early activation of the hypothalamic-pituitary-gonadal axis in the absence of
identifiable central lesions. Mutations of the makorin RING finger 3 (MKRN3) gene
are associated with iCPP. We aimed to assess the frequency of MKRN3 mutations in
iCPP and to compare the phenotypes of patients with and without MKRN3 mutations.
DESIGN: An observational study was carried out on patients recruited at pediatric
hospitals in France and Italy. Forty-six index CPP cases were screened for
mutations in the MKRN3 coding sequence: 28 index cases of familial cases and 18
cases did not report any familial history of CPP. The endocrine phenotype was
compared between MKRN3 mutated and non-mutated patients. RESULTS: MKRN3 mutations
were identified in one sporadic and 13 familial cases. We identified five new
heterozygous missense mutations predicted to be deleterious for protein function
and two frameshift mutations, one new and the other recurrent, predicted to
result in truncated proteins. Age at puberty onset varied very little among
patients with MKRN3 mutations and puberty occurred earlier in these patients than
in those without MKRN3 mutations (6.0 years (5.4-6.0) vs 7.0 years (6.0-7.0),
P=0.01). CONCLUSIONS: MKRN3 mutations are common in familial iCPP. MKRN3 is one
of the gatekeepers of the postnatal activation of the gonadotropic axis.
PMID- 26431554
TI - Options in the Management of Reduced Vision in a Case of Ectopia Lentis.
PMID- 26431555
TI - Black Dots and the Evil Eye! Bitot's spots.
PMID- 26431556
TI - Liquid Crystals--Transformer That Meets the Eye.
PMID- 26431557
TI - Macular Thickness in Highly Myopic Children.
PMID- 26431558
TI - Familial Exudative Vitreoretinopathy: Presentation in the First Week of Life.
PMID- 26431559
TI - Mizuo Nakamura Phenomenon.
PMID- 26431560
TI - Bilateral Congenital Posterior Capsular Defects and Ectopic Cataracts.
AB - Preexisting posterior capsular defects are rare and can be associated with
infantile cataracts. The authors review possible etiologies of this condition and
emphasize the importance of cautious preoperative planning and surgery.
PMID- 26431561
TI - Debris ingestion by the Antillean Manatee (Trichechus manatus manatus).
AB - The Antillean manatee inhabits coastal regions of North and Northeastern Brazil
and currently is considered an endangered species in the country. Aiming to
gather information for the development of public policies focusing on the
conservation of manatees, the National Center for Research and Conservation of
Aquatic Mammals of the Chico Mendes Institute for Biodiversity has been rescuing,
rehabilitating and releasing these mammals since the 1980s. Over the last 36
years, 40 manatees were released by the CMA/ICMBio and four of them were rescued
again due to debris ingestion. Two of these manatees died and the other two were
taken back into captivity for a new rehabilitation process. The four mammals had
confirmed diagnosis of plastic debris ingestion. These findings demonstrate that
the environment where the manatees live after being released had a significant
amount of garbage which may hinder the success of the species conservation in
Brazil.
PMID- 26431563
TI - Mitochondrial Cell Death Pathways in Caenorhabiditis elegans.
AB - Programmed cell death is an evolutionarily conserved process essential for animal
development and tissue homeostasis. Mitochondria have been demonstrated to play a
central role in regulating both the activation and the execution of apoptosis. In
particular, mitochondria release multiple proapoptotic factors from its
intermembrane space, leading to both caspase-dependent and -independent cell
death. Despite the pivotal roles of invertebrate animal models, Caenorhabiditis
elegans and Drosophila melanogaster, in deciphering conserved pathways and
mechanisms of programmed cell death, the importance of mitochondria to apoptosis
of invertebrates remains elusive and largely unexplored. Recent studies have
corroborated significant association between mitochondria and apoptosis in C.
elegans, making it a thrust area of investigations. In this review, we detail the
roles of mitochondrial proteins in mediating execution of cell death in C.
elegans, including chromosome fragmentation, phosphatidylserine externalization,
and elimination of mitochondria, and discuss the potential roles of mitochondria
in the activation of C. elegans cell death. The combination of traditional
powerful genetic tools and the emergence of the multiple new reverse genetic
techniques, including the highly efficient CRISPR/Cas9 gene-editing method,
should make C. elegans an ideal animal model for analyzing mitochondrial cell
death pathways and associated regulatory mechanisms.
PMID- 26431564
TI - Autophagy in Cell Life and Cell Death.
AB - Macroautophagy (hereafter referred to as autophagy) is a process used by the cell
to deliver cytoplasmic components to the lysosome for degradation. Autophagy is
most often associated with cell survival, as it provides cells with molecular
building blocks during periods of nutrient deprivation and also aids in the
elimination of damaged organelles and protein aggregates. However, autophagy has
also been implicated in cell death. Here, we review what is known about
autophagy, its regulation, its role both in cell life and cell death, and what is
known about autophagic cell death in vivo.
PMID- 26431565
TI - The End of the Beginning: Cell Death in the Germline.
AB - Programmed cell death occurs in the germline of many organisms, both as an
essential part of development and throughout adult life. Germline cell death can
be apoptotic or nonapoptotic, depending on the stimulus or stage of development.
Here, we focus on the Drosophila ovary, which is a powerful model for studying
diverse types of cell death. In Drosophila, the death of primordial germ cells
occurs normally during embryonic development, and germline nurse cells are
programmed to die during oocyte development in adult flies. Cell death of
previtellogenic egg chambers in adults can also be induced by starvation or other
environmental cues. Mid-oogenesis seems to be particularly sensitive to such cues
and has been proposed to serve as a checkpoint to avoid the energetically
expensive cost of egg production. After the germline dies in mid-oogenesis, the
remnants are engulfed by an epithelial layer of follicle cells; thus, the fly
ovary also serves as a highly tractable model for engulfment by epithelial cells.
These examples of cell death in the fly ovary share many similarities to the
types of cell death seen in the mammalian germline. Recent progress in
elucidating the molecular mechanisms of cell death in the germline is discussed.
PMID- 26431562
TI - Cell Death in C. elegans Development.
AB - Cell death is a common and important feature of animal development, and cell
death defects underlie many human disease states. The nematode Caenorhabditis
elegans has proven fertile ground for uncovering molecular and cellular processes
controlling programmed cell death. A core pathway consisting of the conserved
proteins EGL-1/BH3-only, CED-9/BCL2, CED-4/APAF1, and CED-3/caspase promotes most
cell death in the nematode, and a conserved set of proteins ensures the
engulfment and degradation of dying cells. Multiple regulatory pathways control
cell death onset in C. elegans, and many reveal similarities with tumor formation
pathways in mammals, supporting the idea that cell death plays key roles in
malignant progression. Nonetheless, a number of observations suggest that our
understanding of developmental cell death in C. elegans is incomplete. The
interaction between dying and engulfing cells seems to be more complex than
originally appreciated, and it appears that key aspects of cell death initiation
are not fully understood. It has also become apparent that the conserved
apoptotic pathway is dispensable for the demise of the C. elegans linker cell,
leading to the discovery of a previously unexplored gene program promoting cell
death. Here, we review studies that formed the foundation of cell death research
in C. elegans and describe new observations that expand, and in some cases
remodel, this edifice. We raise the possibility that, in some cells, more than
one death program may be needed to ensure cell death fidelity.
PMID- 26431566
TI - The HOX-Apoptosis Regulatory Interplay in Development and Disease.
AB - Apoptosis is a cellular suicide program, which is on the one hand used to remove
superfluous cells thereby promoting tissue or organ morphogenesis. On the other
hand, the programmed killing of cells is also critical when potentially harmful
cells emerge in a developing or adult organism thereby endangering survival. Due
to its critical role apoptosis is tightly controlled, however so far, its
regulation on the transcriptional level is less studied and understood. Hox
genes, a highly conserved gene family encoding homeodomain transcription factors,
have crucial roles in development. One of their prominent functions is to shape
animal body plans by eliciting different developmental programs along the
anterior-posterior axis. To this end, Hox proteins transcriptionally regulate
numerous processes in a coordinated manner, including cell-type specification,
differentiation, motility, proliferation as well as apoptosis. In this review, we
will focus on how Hox proteins control organismal morphology and function by
regulating the apoptotic machinery. We will first focus on well-established
paradigms of Hox-apoptosis interactions and summarize how Hox transcription
factors control morphological outputs and differentially shape tissues along the
anterior-posterior axis by fine-tuning apoptosis in a healthy organism. We will
then discuss the consequences when this interaction is disturbed and will
conclude with some ideas and concepts emerging from these studies.
PMID- 26431567
TI - Programmed Cell Death and Caspase Functions During Neural Development.
AB - Programmed cell death (PCD) is a fundamental component of nervous system
development. PCD serves as the mechanism for quantitative matching of the number
of projecting neurons and their target cells through direct competition for
neurotrophic factors in the vertebrate peripheral nervous system. In addition,
PCD plays roles in regulating neural cell numbers, canceling developmental errors
or noise, and tissue remodeling processes. These findings are mainly derived from
genetic studies that prevent cells from dying by apoptosis, which is a major form
of PCD and is executed by activation of evolutionarily conserved cysteine
protease caspases. Recent studies suggest that caspase activation can be
coordinated in time and space at multiple levels, which might underlie
nonapoptotic roles of caspases in neural development in addition to apoptotic
roles.
PMID- 26431568
TI - Regulation of Cell Death by IAPs and Their Antagonists.
AB - Inhibitors of apoptosis (IAPs) family of genes encode baculovirus IAP-repeat
domain-containing proteins with antiapoptotic function. These proteins also
contain RING or UBC domains and act by binding to major proapoptotic factors and
ubiquitylating them. High levels of IAPs inhibit caspase-mediated apoptosis. For
these cells to undergo apoptosis, IAP function must be neutralized by IAP
antagonists. Mammalian IAP knockouts do not exhibit obvious developmental
phenotypes, but the cells are more sensitized to apoptosis in response to injury.
Loss of the mammalian IAP-antagonist ARTS results in reduced stem cell apoptosis.
In addition to the antiapoptotic properties, IAPs regulate the innate immune
response, and the loss of IAP function in humans is associated with
immunodeficiency. The roles of IAPs in Drosophila apoptosis regulation are more
apparent, where the loss of IAP1, or the expression of IAP-antagonists in
Drosophila cells, is sufficient to trigger apoptosis. In this organism, apoptosis
as a fate is conferred by the transcriptional induction of the IAP-antagonists.
Many signaling pathways often converge on shared enhancer regions of IAP
antagonists. Cell death sensitivity is further regulated by posttranscriptional
mechanisms, including those regulated by kinases, miRs, and ubiquitin ligases.
These mechanisms are employed to eliminate damaged or virus-infected cells, limit
neuroblast (neural stem cell) numbers, generate neuronal diversity, and sculpt
tissue morphogenesis.
PMID- 26431569
TI - Ubiquitin-Mediated Regulation of Cell Death, Inflammation, and Defense of
Homeostasis.
AB - Cell death and inflammation are ancient processes of fundamental biological
importance in both normal physiology and human disease pathologies. The recent
observation that apoptosis regulatory components have dual roles in cell death
and inflammation suggests that these proteins function, not primarily to kill,
but to coordinate tissue repair and remodeling. This perspective unifies cell
death components as positive regulators of tissue repair that replaces
malfunctioning or damaged tissues and enhances the resilience of epithelia to
insult. It is now recognized that cells that die by apoptosis do not do so
silently, but release a variety of paracrine signals to communicate with their
cellular environment to ensure tissue regeneration, and wound healing. Moreover,
inflammatory signaling pathways, such as those emanating from the TNF receptor or
Toll-related receptors, take part in cell competition to eliminate
developmentally aberrant clones. Ubiquitylation has emerged as crucial mediator
of signal transduction in cell death and inflammation. Here, we focus on recent
advances on ubiquitin-mediated regulation of cell death and inflammation, and how
this is used to regulate the defense of homeostasis.
PMID- 26431572
TI - Apoptotic Cell Clearance in Development.
AB - Programmed cell death and its specific form apoptosis play an important role
during development of multicellular organisms. They are crucial for morphogenesis
and organ sculpting as well as for adjusting cell number in different systems.
Removal of apoptotic cells is the last critical step of apoptosis. Apoptotic
cells are properly and efficiently recognized and eliminated through
phagocytosis, which is performed by professional and nonprofessional phagocytes.
Phagocytosis of apoptotic cells or apoptotic cell clearance is a dynamic
multistep process, involving interactions between phagocytic receptors and
ligands on apoptotic cells, which are highly conserved in evolution. However,
this process is extremely redundant in mammals, containing multiple factors
playing similar roles in the process. Using model organisms such as
Caenorhabditis elegans, Drosophila melanogaster, zebrafish, and mouse permits
addressing fundamental questions in developmental cell clearance by a
comprehensive approach including powerful genetics and cell biological tools
enriched by live imaging. Recent studies in model organisms have enhanced
significantly our understanding of the molecular and cellular basis of apoptotic
cell clearance during development. Here, we review the current knowledge and
illuminate the great potential of the research performed in genetic models, which
opens new directions in developmental biology.
PMID- 26431571
TI - Clearance of Apoptotic Cells and Pyrenocytes.
AB - Apoptotic cells are engulfed and digested by macrophages to maintain homeostasis
in animals. If dead cells are not engulfed swiftly, they undergo secondary
necrosis and release intracellular components that activate the immune system.
Apoptotic cells are efficiently cleared due to phosphatidylserine (PtdSer)
exposed on the cell surface that acts as an "eat me" signal. PtdSer is exposed
through the activation of phospholipid scramblase and the inactivation of
phospholipid flippase, which are both caspase-mediated events. Macrophages
express a variety of molecules to recognize PtdSer, and use a sophisticated
mechanism to engulf apoptotic cells. In red blood cells, the nucleus is lost when
it is extruded as a pyrenocyte during definitive erythropoiesis. These
pyrenocytes (nuclei surrounded by plasma membrane) also expose PtdSer on their
surface and are efficiently engulfed by macrophages in a PtdSer-dependent manner.
Macrophages transfer the engulfed apoptotic cell or pyrenocyte into lysosomes,
where the components of the dead cell or pyrenocyte are degraded. If lysosomes
cannot digest the DNA from apoptotic cells or pyrenocytes, the undigested DNA
accumulates in the lysosome and activates macrophages to produce type I
interferon (IFN) via a STING-dependent pathway; in embryos, this causes severe
anemia. Here, we discuss how macrophages clear apoptotic cells and pyrenocytes.
PMID- 26431570
TI - The Sound of Silence: Signaling by Apoptotic Cells.
AB - Apoptosis is a carefully choreographed process of cellular self-destruction in
the absence of inflammation. During the death process, apoptotic cells actively
communicate with their environment, signaling to both their immediate neighbors
as well as distant sentinels. Some of these signals direct the anti-inflammatory
immune response, instructing specific subsets of phagocytes to participate in the
limited and careful clearance of dying cellular debris. These immunomodulatory
signals can also regulate the activation state of the engulfing phagocytes. Other
signals derived from apoptotic cells contribute to tissue growth control with the
common goal of maintaining tissue integrity. Derangements in these growth control
signals during prolonged apoptosis can lead to excessive cell loss or
proliferation. Here, we highlight some of the most intriguing signals produced by
apoptotic cells during the course of normal development as well as during
physiological disturbances such as atherosclerosis and cancer.
PMID- 26431573
TI - The Morphogenetic Role of Apoptosis.
AB - Beyond safeguarding the organism from cell misbehavior and controlling cell
number, apoptosis (or programmed cell death) plays key roles during animal
development. In particular, it has long been acknowledged that apoptosis
participates in tissue remodeling. Yet, until recently, this contribution to
morphogenesis was considered as "passive," consisting simply in the local removal
of unnecessary cells leading to a new shape. In recent years, applying live
imaging methods to study the dynamics of apoptosis in various contexts has
considerably modified our vision, revealing that in fact, dying cells remodel
their neighborhood actively. Here, we first focus on the intrinsic cellular
properties of apoptotic cells during their dismantling, in particular the role of
the cytoskeleton during their characteristic morphological changes. Second, we
review the various roles of apoptosis during developmental morphogenetic
processes and pinpoint the crucial role of live imaging in revealing new
concepts, in particular apoptosis as a generator of mechanical forces to control
tissue dynamics.
PMID- 26431574
TI - Preface.
PMID- 26431575
TI - Refined 9-lead total QRS voltage criteria may offer a better diagnostic accuracy
for left ventricular hypertrophy.
PMID- 26431576
TI - No benefit to die from cancer with healthy coronary arteries, except in France.
PMID- 26431577
TI - Predictors of short- and long-term outcomes of Takotsubo cardiomyopathy.
AB - Takotsubo cardiomyopathy (TC) is a reversible cardiomyopathy with a benign short
term prognosis but is associated with recurrence rate of 10%. Clinical variables
that predict long-term mortality and recurrence are unknown; 56 consecutive
patients presenting to a single urban medical center who fulfilled the Mayo
Clinic criteria for the diagnosis of TC were included. Patients were followed
with 100% completeness; >60 clinical factors were analyzed, including
presentation, treatment, electrocardiogram, and echocardiographic, angiographic,
and demographic variables. Survival analysis was performed using the Kaplan-Meier
function and Cox proportional hazards regression models. There were 15 deaths
during follow-up: 5 in-hospital, 4 before 90 days, and 6 after 90 days. Mean
survival was 4.47 years (95% confidence interval 3.81 to 5.13). All short-term
survivors had repeat ejection fraction evaluation demonstrating improvement; 45
of 56 patients were women and 96% were postmenopausal. The nonfatal recurrence
rate was 1.8%. QTc interval at presentation was the factor most strongly
predictive of overall outcome, after intubation. All patients with mortality had
QTc intervals between 400 and 550 ms. In conclusion, this study demonstrates the
prognostic significance of QTc prolongation at presentation in TC. Because the
cause of TC involves intense catecholamine release and hyperadrenergic tone, the
QTc may reflect the individual impact on myocardial repolarization and the
balance between sympathetic innervation and parasympathetic compensation. In
conclusion, in this series, TC was associated with an 8.9% in-hospital mortality,
an additional 17.9% mortality after discharge, and a nonfatal recurrence rate of
1.8%. Moreover, the QTc on presentation with TC was predictive of outcome.
PMID- 26431578
TI - Assessment of dose error due to nylon mesh of treatment couch.
AB - PURPOSE: This study aims at the assessment of dose error in patients undergoing
radiotherapy due to treatment couch of Co-60 teletherapy unit. MATERIALS AND
METHODS: In this study beam attenuation due to treatment couch of Co-60 unit was
measured in air for different gantry angles and field sizes.
Polymethylmethacrylate (PMMA) phantom was used to estimate the effect of depth on
attenuation. Impact of couch on surface dose was also evaluated. RESULTS: Beam
attenuation due to couch was in the range of 0.5-28% for different gantry angles
with standard field size of 10 * 10 cm(2) with optimum position of metallic
cranks. Maximum attenuation (29%) was observed with smallest field size i.e. 5 *
5 cm(2). Beam attenuation has been found higher in phantom as compared to that in
air However, no particular trend of attenuation has been noted with varying depth
of phantom. A 6% increase in surface dose has also been observed due to couch
insertion for normal beam incidence. Maximum error of 80% is also note-worthy for
most unfavorable situation of irradiation at 180 degree through the metallic
cranks. CONCLUSION: It has been determined that ignoring the treatment couch and
its accessories can result in dose error of 0.5-80%, depending on gantry angle,
field size and position of couch accessories. Therefore, consideration of dose
error due to couch during treatment planning is recommended.
PMID- 26431579
TI - Quantization accuracy of short-duration respiratory-gated PET/CT acquisitions.
AB - PURPOSE: PET/CT acquisitions are affected by physiological motion, which lowers
the quantization accuracy. Respiratory-gated PET/CT methods require a long
acquisition time, which may not be compatible with the clinical schedule. The
objective of the present study was to assess the quantization accuracy of short
duration, respiratory-gated PET acquisitions and processing with the "CT-based"
methodology developed in our laboratory. METHODS: Quantization accuracy was first
assessed in a phantom study. A standard ("Ungated") PET/CT acquisition was
followed by a 10-minute list-mode acquisition with simultaneous respiratory
signal recording and a short breath-hold CT scan (BH-CT). These acquisitions were
repeated 10 times. For the CT-based images, we reconstructed (i) 10 full-duration
(FD-CT-based) volumes that took account of all events recorded in the position
defined by BH-CT and (ii) 10 short-duration (SD-CT-based) volumes based on only
30 seconds of selected events. Using these volumes, we performed a bias-variance
analysis to assess the effects of respiration-motion reduction and the counting
statistics on the quantization accuracy. We also applied Ungated, FD- and SD-CT
based methods to 16 patients (21 pulmonary lesions) and measured the maximum
standardized uptake (SUVmax) values. RESULTS: The bias values were 71%, 40% and
44% for Ungated, FD- and SD-CT-based images, respectively. In the clinical study,
there was a statistically significant difference in SUVmax between Ungated images
and both the CT-Based images (p < 0.02) but not between the FD-CT-Based and SD-CT
Based images (p = 0.42). CONCLUSION: Our findings demonstrated that the
additional acquisition time required by the CT-based method can be reduced
without altering quantitative accuracy.
PMID- 26431580
TI - Hematopoietic prostaglandin D synthase defines a proeosinophilic pathogenic
effector human T(H)2 cell subpopulation with enhanced function.
AB - BACKGROUND: IL-5(+) pathogenic effector T(H)2 (peT(H)2) cells are a T(H)2 cell
subpopulation with enhanced proinflammatory function that has largely been
characterized in murine models of allergic inflammation. OBJECTIVE: We sought to
identify phenotype markers for human peT(H)2 cells and characterize their
function in patients with allergic eosinophilic inflammatory diseases. METHODS:
Patients with eosinophilic gastrointestinal disease (EGID), patients with atopic
dermatitis (AD), and nonatopic healthy control (NA) subjects were enrolled.
peT(H)2 and conventional T(H)2 (cT(H)2) cell phenotype, function, and cytokine
production were analyzed by using flow cytometry. Confirmatory gene expression
was measured by using quantitative RT-PCR. Prostaglandin D2 levels were measured
with ELISA. Gut T(H)2 cells were obtained by means of esophagogastroduodenoscopy.
RESULTS: peT(H)2 cells were identified as chemoattractant receptor-homologous
molecule expressed on T(H)2 cells-positive (CRTH2(+)), hematopoietic
prostaglandin D synthase-positive CD161(hi) CD4 T cells. peT(H)2 cells expressed
significantly greater IL-5 and IL-13 than did hematopoietic prostaglandin D
synthase-negative and CD161(-) cT(H)2 cells. peT(H)2 cells were highly correlated
with blood eosinophilia (r = 0.78-0.98) and were present in 30- to 40-fold
greater numbers in subjects with EGID and those with AD versus NA subjects.
Relative to cT(H)2 cells, peT(H)2 cells preferentially expressed receptors for
thymic stromal lymphopoietin, IL-25, and IL-33 and demonstrated greater
responsiveness to these innate pro-TH2 cytokines. peT(H)2 but not cT(H)2 cells
produced prostaglandin D2. In patients with EGID and those with AD, peT(H)2 cells
expressed gut- and skin-homing receptors, respectively. There were significantly
greater numbers of peT(H)2 cells in gut tissue from patients with EGID versus NA
subjects. CONCLUSION: peT(H)2 cells are the primary functional proinflammatory
human T(H)2 cell subpopulation underlying allergic eosinophilic inflammation. The
unambiguous phenotypic identification of human peT(H)2 cells provides a powerful
tool to track these cells in future pathogenesis studies and clinical trials.
PMID- 26431581
TI - Critical link between glycogen synthase kinase 3beta and forkhead box P3 in
patients with chronic rhinosinusitis with nasal polyps.
PMID- 26431582
TI - Petrolatum: Barrier repair and antimicrobial responses underlying this "inert"
moisturizer.
AB - BACKGROUND: Petrolatum is a common moisturizer often used in the prevention of
skin infections after ambulatory surgeries and as a maintenance therapy of atopic
dermatitis (AD). However, the molecular responses induced by petrolatum in the
skin have never been assessed. OBJECTIVE: We sought to define the cutaneous
molecular and structural effects induced by petrolatum. METHODS: Thirty-six
healthy subjects and 13 patients with moderate AD (mean SCORAD score, 39) were
studied by using RT-PCR, gene arrays, immunohistochemistry, and
immunofluorescence performed on control skin, petrolatum-occluded skin, and skin
occluded with a Finn chamber only. RESULTS: Significant upregulations of
antimicrobial peptides (S100A8/fold change [FCH], 13.04; S100A9/FCH, 11.28;
CCL20/FCH, 8.36; PI3 [elafin]/FCH, 15.40; lipocalin 2/FCH, 6.94, human beta
defensin 2 [DEFB4A]/FCH, 4.96; P < .001 for all) and innate immune genes (IL6,
IL8, and IL1B; P < .01) were observed in petrolatum-occluded skin compared with
expression in both control and occluded-only skin. Application of petrolatum also
induced expression of key barrier differentiation markers (filaggrin and
loricrin), increased stratum corneum thickness, and significantly reduced T-cell
infiltrates in the setting of "normal-appearing" or nonlesional AD skin, which is
known to harbor barrier and immune defects. CONCLUSIONS: Petrolatum robustly
modulates antimicrobials and epidermal differentiation barrier measures. These
data shed light on the beneficial molecular responses of petrolatum in barrier
defective states, such as AD and postoperative wound care.
PMID- 26431583
TI - Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut
microbiome underlying atopic dermatitis.
AB - BACKGROUND: Atopic dermatitis (AD) is a serious global epidemic associated with a
modern lifestyle. OBJECTIVE: Although aberrant interactions between gut microbes
and the intestinal immune system have been implicated in this skin disease, the
nature of the microbiome dysfunction underlying the disease remains unclear.
METHODS: The gut microbiome from 132 subjects, including 90 patients with AD, was
analyzed by using 16S rRNA gene and metagenome sequence analyses. Reference
genomes from the Human Microbiome Project and the KEGG Orthology database were
used for metagenome analyses. Short-chain fatty acids in fecal samples were
compared by using gas chromatographic-mass spectrometric analyses. RESULTS: We
show that enrichment of a subspecies of the major gut species Faecalibacterium
prausnitzii is strongly associated with AD. In addition, the AD microbiome was
enriched in genes encoding the use of various nutrients that could be released
from damaged gut epithelium, reflecting a bloom of auxotrophic bacteria. Fecal
samples from patients with AD showed decreased levels of butyrate and propionate,
which have anti-inflammatory effects. This is likely a consequence of an
intraspecies compositional change in F prausnitzii that reduces the number of
high butyrate and propionate producers, including those related to the strain A2
165, a lack of which has been implicated in patients with Crohn disease.
CONCLUSIONS: The data suggest that feedback interactions between dysbiosis in F
prausnitzii and dysregulation of gut epithelial inflammation might underlie the
chronic progression of AD by resulting in impairment of the gut epithelial
barrier, which ultimately leads to aberrant TH2-type immune responses to
allergens in the skin.
PMID- 26431584
TI - Characteristics and functions of lipid droplets and associated proteins in
enterocytes.
AB - Cytosolic lipid droplets (LDs) are observed in enterocytes of jejunum during
lipid absorption. One important function of the intestine is to secrete
chylomicrons, which provide dietary lipids throughout the body, from digested
lipids in meals. The current hypothesis is that cytosolic LDs in enterocytes
constitute a transient pool of stored lipids that provides lipids during
interprandial period while lowering chylomicron production during the post
prandial phase. This smoothens the magnitude of peaks of hypertriglyceridemia.
Here, we review the composition and functions of lipids and associated proteins
of enterocyte LDs, the known physiological functions of LDs as well as the role
of LDs in pathological processes in the context of the intestine.
PMID- 26431585
TI - Kinase active Misshapen regulates Notch signaling in Drosophila melanogaster.
AB - Notch signaling pathway represents a principal cellular communication system that
plays a pivotal role during development of metazoans. Drosophila misshapen (msn)
encodes a protein kinase, which is related to the budding yeast Ste20p (sterile
20 protein) kinase. In a genetic screen, using candidate gene approach to
identify novel kinases involved in Notch signaling, we identified msn as a novel
regulator of Notch signaling. Data presented here suggest that overexpression of
kinase active form of Msn exhibits phenotypes similar to Notch loss-of-function
condition and msn genetically interacts with components of Notch signaling
pathway. Kinase active form of Msn associates with Notch receptor and regulate
its signaling activity. We further show that kinase active Misshapen leads to
accumulation of membrane-tethered form of Notch. Moreover, activated Msn also
depletes Armadillo and DE-Cadherin from adherens junctions. Thus, this study
provides a yet unknown mode of regulation of Notch signaling by Misshapen.
PMID- 26431587
TI - Fluctuating diplopia as an initial manifestation of polycythemia vera.
PMID- 26431586
TI - PKCepsilon as a novel promoter of skeletal muscle differentiation and
regeneration.
AB - INTRODUCTION: Satellite cells are muscle resident stem cells and are responsible
for muscle regeneration. In this study we investigate the involvement of
PKCepsilon during muscle stem cell differentiation in vitro and in vivo. Here, we
describe the identification of a previously unrecognized role for the PKCepsilon
HMGA1 signaling axis in myoblast differentiation and regeneration processes.
METHODS: PKCepsilon expression was modulated in the C2C12 cell line and primary
murine satellite cells in vitro, as well as in an in vivo model of muscle
regeneration. Immunohistochemistry and immunofluorescence, RT-PCR and shRNA
silencing techniques were used to determine the role of PKCepsilon and HMGA1 in
myogenic differentiation. RESULTS: PKCepsilon expression increases and
subsequently re-localizes to the nucleus during skeletal muscle cell
differentiation. In the nucleus, PKCepsilon blocks Hmga1 expression to promote
Myogenin and Mrf4 accumulation and myoblast formation. Following in vivo muscle
injury, PKCepsilon accumulates in regenerating, centrally-nucleated myofibers.
Pharmacological inhibition of PKCepsilon impairs the expression of two crucial
markers of muscle differentiation, namely MyoD and Myogenin, during injury
induced muscle regeneration. CONCLUSION: This work identifies the PKCepsilon
HMGA1 signaling axis as a positive regulator of skeletal muscle differentiation.
PMID- 26431588
TI - Moderate consumption of white and fortified wine is associated with reduced odds
of diabetic retinopathy.
AB - AIM: To explore the association between alcohol consumption and the severity of
diabetic retinopathy (DR). METHODS: In this cross-sectional study, patients with
type 2 diabetes answered questions on consumption of low and full-strength beer,
white wine/champagne, red wine, fortified wines, and spirits. Never, moderate and
high consumption of each alcoholic beverage, and overall alcoholic beverage
consumption, were defined as <1, 1-14 and >14 standard drinks/week, respectively.
DR was categorized into none; non vision-threatening DR (VTDR) and VTDR.
Multivariable logistic regression determined the associations between alcohol
consumption and DR. RESULTS: Of the 395 participants (mean age+/-SD [standard
deviation] 65.9+/-10.4years; males=253), 188 (47.6%) consumed alcohol and 235
(59.5%) had any DR. Compared to no alcohol consumption, moderate alcohol
consumption (overall) was significantly associated with reduced odds of any DR
(OR=0.47, 95% CI [confidence interval] 0.26-0.85). Moderate consumption of white
wine/champagne or fortified wine was also associated with reduced odds of any DR
(OR=0.48, 95% CI 0.25-0.91, and OR=0.15, 95% CI 0.04-0.62, respectively). Similar
results were observed for non-VTDR and VTDR. CONCLUSIONS: The amount and type of
alcohol are associated with risk of DR in patients with type 2 diabetes. A
longitudinal study is needed to assess the protective effect of alcohol
consumption and DR.
PMID- 26431589
TI - Imaging Reporters for Proteasome Activity Identify Tumor- and Metastasis
Initiating Cells.
AB - Tumor-initiating cells, also designated as cancer stem cells, are proposed to
constitute a subpopulation of malignant cells central to tumorigenesis,
metastasis, and treatment resistance. We analyzed the activity of the proteasome,
the primary organelle for targeted protein degradation, as a marker of tumor- and
metastasis-initiating cells. Using human and mouse breast cancer cells expressing
a validated fluorescent reporter, we found a small subpopulation of cells with
low proteasome activity that divided asymmetrically to produce daughter cells
with low or high proteasome activity. Breast cancer cells with low proteasome
activity had greater local tumor formation and metastasis in immunocompromised
and immunocompetent mice. To allow flexible labeling of cells, we also developed
a new proteasome substrate based on HaloTag technology. Patient-derived
glioblastoma cells with low proteasome activity measured by the HaloTag reporter
show key phenotypes associated with tumor-initiating cells, including expression
of a stem cell transcription factor, reconstitution of the original starting
population, and enhanced neurosphere formation. We also show that patient-derived
glioblastoma cells with low proteasome activity have higher frequency of tumor
formation in mouse xenografts. These studies support proteasome function as a
tool to investigate tumor- and metastasis-initiating cancer cells and a potential
biomarker for outcomes in patients with several different cancers.
PMID- 26431590
TI - Comparative study of the clinical features of patients with a tubo-ovarian
abscess and patients with severe pelvic inflammatory disease.
AB - OBJECTIVE: To determine the clinical characteristics that indicate the presence
of tubo-ovarian abscess (TOA) among patients with severe pelvic inflammatory
disease (PID). METHODS: An observational cohort study was performed from October
2011 to March 2013. The study included all patients with a diagnosis of TOA and
PID admitted to a university hospital in Mexico. A complete medical history and
physical examination were performed, and laboratory studies were reviewed. A
logistic regression analysis was performed on variables with statistical
significance. RESULTS: Overall, 26 patients with PID and TOA (TOA group) and 26
with PID without TOA (PID group) were included in the study. Significant
differences between patients with TOA and PID were found with regard to the
patients' age (39.3years vs 33.1years; P=0.04), educational level (only
elementary, 13 [50%] vs 5 [19%]; P=0.14), presentation with fever (23 [88%] vs 16
[62%]; P=0.025), white blood cell count (21.8*10(9)/L vs 14.9*10(9)/L; P<0.001),
number of deliveries (2.2 vs 1.1; P=0.01), and presence of diarrhea (16 [62%] vs
5 [19%]; P<0.001). The triad of fever, leukocytosis, and diarrhea was positively
related to the presence of TOA. CONCLUSION: The triad of fever, leukocytosis, and
diarrhea should alert clinicians to the possibility of TOA formation in patients
with PID.
PMID- 26431591
TI - Role of oxidative stress and serum lipid levels in stable chronic obstructive
pulmonary disease.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been associated with
increased oxidative stress or reduced antioxidant resources. The main goal of
this study was to evaluate the levels of serum ischemia-modified albumin (IMA),
oxidized low-density lipoprotein (ox-LDL), total oxidant status (TOS), and total
antioxidant status in patients with stable COPD, compared with a control group.
METHODS: This study was performed on 51 patients with stable COPD (42 men and 9
women; mean age 56.92 +/- 3.0 years) and 45 healthy control participants (32 men
and 13 women; 54.8 +/- 3.8 years). The levels of serum lipids, IMA, total
antioxidant status, TOS, and ox-LDL were measured in all participants. RESULTS:
The levels of serum IMA, ox-LDL, and TOS were significantly higher in patients
with COPD than those in control individuals. There was no difference between the
levels of serum total antioxidant status, triglycerides, total cholesterol, and
low-density lipoprotein cholesterol (LDL-C) of patients with COPD and those of
control individuals. Serum high-density lipoprotein cholesterol levels were
significantly lower in patients with COPD than in control individuals.
CONCLUSION: Our study indicated that serum IMA, ox-LDL, and TOS may be increased
as a result of chronic hypoxia, inflammation, and oxidative stress in patients
with severe and very severe stable COPD. Our findings also revealed that IMA is
higher in patients with Global Initiative for Chronic Obstructive Lung Disease
Stages II, III, and IV, while TOS and ox-LDL are higher in patients with Global
Initiative for Chronic Obstructive Lung Disease Stage IV. Measurements of serum
IMA, TOS, and ox-LDL levels may be useful markers in the evaluation of stable
COPD.
PMID- 26431592
TI - Changes in platelet function independent of pharmacotherapy following coronary
intervention in non-ST-elevation myocardial infarction patients.
AB - BACKGROUND: High on treatment platelet reactivity (HTPR) is common in patients
receiving clopidogrel following an acute coronary syndrome (ACS); it's also
associated with increased morbidity and mortality. More potent and predictable
antiplatelet drugs have addressed this issue at the expense of increased
bleeding. Identification of HTPR and the targeted use of more potent antiplatelet
drugs has, so far, broadly failed. We investigate this approach in terms of the
timing of platelet function testing and how this can impact on the ability of
these bedside tests to predict HTPR around the time of coronary intervention.
METHODS: High risk ACS patients treated with 5 days of clopidogrel had platelet
function assessed using the multiple electrode aggregometry system (MEA) pre,
post and 24 h following percutaneous coronary intervention (PCI). Simultaneous
detailed analysis of platelet status was undertaken with quantification of
platelet bound and soluble p-selectin and mass spectrometry quantification of the
eicosanoid 12-HETE. RESULTS: As assessed by MEA 40.5% of patients had HTPR pre
PCI; mean aggregation units (AU) in response to ADP were 499.1 +/- 46.3 pre-PCI,
407.6 +/- 37.7 post-PCI and 269.1 +/- 24.6 AU 24 h post-PCI (pre to post PCI p >
0.05, pre to 24 h post-PCI p = 0.0002). This highly significant drop in platelet
reactivity was contrasted with on-going expression of platelet bound p-selectin,
increased soluble p-selectin and rising 12-HETE concentrations. CONCLUSIONS: This
study outlines significant changes in ex-vivo platelet aggregation that occur
within 24 h of PCI in high risk NSTEMI patients using bedside PFT. Whilst there
were no changes in antiplatelet therapy during the study period its clear that
timing is crucial when assessing high on treatment residual platelet activity.
PMID- 26431594
TI - Difficult Biliary Access: Advanced Cannulation and Sphincterotomy Technique.
AB - Many devices and techniques have been developed to assist in cases of difficult
biliary cannulation. Guidewire-assisted cannulation has become the first-line
technique for biliary cannulation. Precut sphincterotomy can be safe and
effective if used soon after encountering difficulty. Pancreatic duct stents are
an important adjunct to reduce the risk of post-endoscopic retrograde
cholangiopancreatography pancreatitis in difficult access. Ultimately,
cannulation success of greater than 95% and complication rates of less than 5% is
the standard that endoscopists doing ERCP should achieve.
PMID- 26431593
TI - Age matters: Developmental stage of Danio rerio larvae influences photomotor
response thresholds to diazinion or diphenhydramine.
AB - Because basic toxicological data is unavailable for the majority of industrial
compounds, High Throughput Screening (HTS) assays using the embryonic and larval
zebrafish provide promising approaches to define bioactivity profiles and
identify potential adverse outcome pathways for previously understudied
chemicals. Unfortunately, standardized approaches, including HTS experimental
designs, for examining fish behavioral responses to contaminants are rarely
available. In the present study, we examined movement behavior of larval
zebrafish over 7 days (4-10 days post fertilization or dpf) during typical
daylight workday hours to determine whether intrinsic activity differed with age
and time of day. We then employed an early life stage approach using the Fish
Embryo Test (FET) at multiple developmental ages to evaluate whether photomotor
response (PMR) behavior differed with zebrafish age following exposure to
diazinon (DZN), a well-studied orthophosphate insecticide, and diphenhydramine
(DPH), an antihistamine that also targets serotonin reuptake transporters and the
acetylcholine receptor. 72h studies were conducted at 1-4, 4-7 and 7-10dpf,
followed by behavioral observations using a ViewPoint system at 4, 7 and 10dpf.
Distance traveled and swimming speeds were quantified; nominal treatment levels
were analytically verified by isotope-dilution LC-MSMS. Larval zebrafish
locomotion displayed significantly different (p<0.05) activity profiles over the
course of typical daylight and workday hours, and these time of day PMR activity
profiles were similar across ages examined (4-10dpf). 10dpf zebrafish larvae were
consistently more sensitive to DPH than either the 4 or 7dpf larvae with an
environmentally realistic lowest observed effect concentration of 200ng/L. Though
ELS and FET studies with zebrafish typically focus on mortality or teratogenicity
in 0-4dpf organisms, behavioral responses of slightly older fish were several
orders of magnitude more sensitive to DPH. Our observations highlight the
importance of understanding the influence of time of day on intrinsic locomotor
activity, and the age-specific hazards of aquatic contaminants to fish behavior.
PMID- 26431595
TI - Endoscopic Retrograde Cholangiopancreatography in Surgically Altered Anatomy.
AB - ERCP in surgically altered anatomy requires the endoscopist to fully understand
the procedural goals and the reconstructed anatomy before proceeding. Altered
anatomy presents a variety of challenges unique to enteroscopy, and others
related to accessing the biliary or pancreatic duct from unusual orientations.
Both side-viewing and forward-viewing endoscopes, as well as single and double
balloon techniques, are available for ERCP in these settings. Endoscope selection
largely depends on the anatomy and length of reconstructed intestinal limbs.
Endoscopist experience with performing ERCP in surgically altered anatomy is the
most important factor for determining outcomes and success rates.
PMID- 26431596
TI - Endoscopic Retrograde Cholangiopancreatography for the Management of Common Bile
Duct Stones and Gallstone Pancreatitis.
AB - Biliary disease is a common cause of acute pancreatitis. Risk stratification for
persistent pancreatobiliary obstruction is important for selecting a treatment
approach. Most common bile duct stones are extracted with standard endoscopic
techniques. However, prior foregut surgery, stones with extreme morphologic
attributes, and at difficult positions within the biliary system are technically
challenging and predict a need for advanced biliary endoscopic techniques.
Surgical common bile duct exploration at the time of cholecystectomy is
appropriate in centers with experience. We outline the options and approach for
the clinician to successfully identify and manage patients with symptomatic
choledocholithiasis with or without biliary pancreatitis.
PMID- 26431597
TI - Diagnosing Biliary Malignancy.
AB - The most common malignant causes of biliary strictures are pancreatic cancer and
cholangiocarcinoma. Differentiating between malignant and benign causes of
biliary strictures has remained a clinical challenge. Endoscopic retrograde
cholangiopancreatography (ERCP) remains the mainstay and first-line method of
tissue diagnosis but has a poor diagnostic yield. This article reviews the causes
of biliary strictures, the initial clinical evaluation of biliary obstruction,
the diagnostic yield of ERCP-based sampling methods, the role of newer tools in
the armamentarium for evaluating strictures, and ways to address the ongoing
challenge of stricture evaluation in patients with primary sclerosing
cholangitis.
PMID- 26431598
TI - Stenting in Malignant Biliary Obstruction.
AB - Decompression of the biliary system in patients with malignant biliary
obstruction has been widely accepted and implemented as part of the care. Despite
a wealth of literature, there remains a significant amount of uncertainty as to
which approach would be most appropriate in different clinical settings. This
review covers stenting of the biliary system in cases of resectable or palliative
malignant biliary obstruction, potential candidates for biliary drainage,
technical aspects of the procedure, as well as management of biliary stent
dysfunction. Furthermore, periprocedural considerations including proper mapping
of the location of obstruction and the use of antibiotics are addressed.
PMID- 26431599
TI - Benign Biliary Strictures and Leaks.
AB - The major causes of benign biliary strictures include surgery, chronic
pancreatitis, primary sclerosing cholangitis, and autoimmune cholangitis. Biliary
leaks mainly occur after surgery and, rarely, abdominal trauma. These conditions
may benefit from a nonsurgical approach in which endoscopic retrograde
cholangiopancreatography (ERCP) plays a pivotal role in association with other
minimally invasive approaches. This approach should be evaluated for any injury
before deciding about the method for repair. ERCP, associated with peroral
cholangioscopy, plays a growing role in characterizing undeterminate strictures,
avoiding both unuseful major surgeries and palliative options that might
compromise any further management.
PMID- 26431600
TI - Preventing Postendoscopic Retrograde Cholangiopancreatography Pancreatitis.
AB - Postendoscopic retrograde cholangiopancreatography pancreatitis is a common and
potentially devastating complication of endoscopic retrograde
cholangiopancreatography. Advances in risk-stratification, patient selection,
procedure technique, and prophylactic interventions have substantially improved
the ability to prevent this complication. This article presents the evidence
based approaches to preventing postendoscopic retrograde cholangiopancreatography
pancreatitis and discusses timely research questions in this important area.
PMID- 26431601
TI - Endoscopic Treatment of Recurrent Acute Pancreatitis and Smoldering Acute
Pancreatitis.
AB - Recurrent acute pancreatitis (RAP) is a challenging condition that can lead to
chronic pancreatitis and long-term morbidity. Etiology-based treatment can
potentially have an impact on the natural history of RAP and its progression to
chronic pancreatitis. In cases of divisum-associated RAP and idiopathic RAP,
several studies have been performed to evaluate the efficacy of endoscopic
therapy in alleviation of symptoms and frequency of AP events. This review
discusses the literature available on these topic as well as touching on the role
of endoscopic therapy in smoldering acute pancreatitis.
PMID- 26431602
TI - Sphincter of Oddi Dysfunction.
AB - This article reviews the diagnosis and management of sphincter of Oddi
dysfunction (SOD), including the various factors to consider before embarking on
endoscopic therapy for SOD. Selection starts with patient education to include
possible patient misconceptions related to symptoms caused by the
pancreaticobiliary sphincter as well as reinforcing the risks associated with the
diagnosis and therapy. The likelihood of relief of recurrent abdominal pain
attributed to SOD is related to the classification of SOD type and a crucial
consideration before considering endoscopic therapy in light of recent evidence.
PMID- 26431603
TI - Pancreatic Endotherapy for Chronic Pancreatitis.
AB - Extracorporeal shock wave lithotripsy is recommended as the first-line therapy
for large (>5-mm) obstructive pancreatic ductal stones. Dominant pancreatic duct
strictures should be initially managed with a wide-bore single plastic stent with
3 monthly exchanges for a year, even in asymptomatic patients. Recent studies
have evaluated multiple plastic and self-expanding covered metal stents for
refractory pancreatic ductal stricture. Pancreatic pseudocysts should be treated
endoscopically with or without endoscopic ultrasound guidance.
PMID- 26431604
TI - Innovations in Intraductal Endoscopy: Cholangioscopy and Pancreatoscopy.
AB - Cholangioscopy was first performed in the 1970s. We now use the term
cholangiopancreatoscopy (CP) to reflect the wider application of these miniature
reusable dual-operator "mother-daughter" endoscope systems and now fully
disposable and digital single-operator optical catheters for evaluating the
biliary or pancreatic duct. Cholangioscopy is an established modality for the
management of large biliary stones and for the diagnosis and exclusion of biliary
tumors. Pancreatoscopy is increasingly being performed to treat difficult
pancreatic duct stones and may be used to distinguish malignant from benign
ductal pathology. This review covers available CP technologies, indications,
technique, efficacy, and complications.
PMID- 26431605
TI - Biliary Tumor Ablation with Photodynamic Therapy and Radiofrequency Ablation.
AB - Within the past two decades, major progress has been made in biliary endoscopy
both with stenting and with ablative therapy. A primary goal in patients with
malignant biliary lesions who are not candidates for surgery is to provide
localized and efficient necrosis of the lesions. This article summarizes the
current literature on biliary tumor ablation with photodynamic therapy and
radiofrequency ablation. Prognosis, treatment technique, potential complications,
treatment efficacy, and controversies are discussed.
PMID- 26431606
TI - Endoscopic Ultrasound-Assisted Pancreaticobiliary Access.
AB - Endoscopic retrograde cholangiopancreatography (ERCP) is the primary approach to
drain an obstructed pancreatic or biliary duct. Failed biliary drainage is
traditionally referred for percutaneous transhepatic biliary drainage or surgical
bypass, which carry significantly higher morbidity and mortality rates compared
with ERCP and transpapillary drainage. Endoscopic ultrasound provides a real-time
imaging platform to access and deliver therapy to organs and tissues outside of
the bowel lumen. The bile and pancreatic ducts can be directly accessed from the
stomach and duodenum, offering an alternative to ERCP when this fails or is not
feasible.
PMID- 26431607
TI - Advances in Therapeutic Endoscopic Retrograde Cholangiopancreatography: Benefits
Far Outweigh the Small Risks.
PMID- 26431608
TI - Advances in Endoscopic Retrograde Cholangiopancreatography.
PMID- 26431609
TI - Kaposi Sarcoma-associated Herpesvirus: mechanisms of oncogenesis.
AB - Kaposi Sarcoma-associated Herpesvirus (KSHV, HHV8) causes three human
malignancies, Kaposi Sarcoma (KS), an endothelial tumor, as well as Primary
Effusion Lymphoma (PEL) and the plasma cell variant of Multicentric Castleman's
Disease (MCD), two B-cell lymphoproliferative diseases. All three cancers occur
primarily in the context of immune deficiency and/or HIV infection, but their
pathogenesis differs. KS most likely results from the combined effects of an
endotheliotropic virus with angiogenic properties and inflammatory stimuli and
thus represents an interesting example of a cancer that arises in an inflammatory
context. Viral and cellular angiogenic and inflammatory factors also play an
important role in the pathogenesis of MCD. In contrast, PEL represents an
autonomously growing malignancy that is, however, still dependent on the
continuous presence of KSHV and the action of several KSHV proteins.
PMID- 26431610
TI - The amount of mandibular setback influence on occlusal force following sagittal
split ramus osteotomy.
AB - PURPOSE: The purpose of this study was to examine the influence between the
magnitude of setback in sagittal split ramus osteotomy (SSRO) and occlusal
contact area and bite force without relapse after surgery. PATIENTS AND METHODS:
Sixty female patients with a diagnosis of mandibular prognathism were divided
into 3 groups according to the magnitude of setback: group 1 (<=5 mm), group 2
(>5 mm but <10 mm), and group 3 (>=10 mm). All patients underwent skeletal
analysis by lateral and frontal cephalogrammetry and measured the occlusal
contact area and bite force by the pressure-sensitive system (Dental Prescale,
Dental Occlusion Pressuregraph FDP-705; Fuji Photo Film Co., Tokyo, Japan)
preoperatively and postoperatively at 1 month, 3 months, 6 months, and 1 year.
RESULTS: There were no significant differences in occlusal contact area and bite
force between the 3 groups. Only group 3 showed a significant difference in
occlusal contact area and bite force between the preoperative and 1-year
measurements. CONCLUSION: The results indicate that the magnitude of setback did
not influence the bite force or occlusal contact area in SSRO.
PMID- 26431611
TI - Transgenerational effects of 17alpha-ethinyl estradiol on anxiety behavior in the
guppy, Poecilia reticulata.
AB - Environmental contaminants can cause alterations that can be transgenerationally
transmitted to subsequent generations. Estrogens are among those contaminants
shown to induce heritable changes that persist over generations in mammals.
Results in other vertebrates are few. We have analyzed the effects on anxiety of
17alpha-ethinyl estradiol (EE2) in the F1 and F2 generations in guppies, Poecilia
reticulata, obtained from F0 fish maternally exposed to 0 or 20ng/L EE2 until
birth. F0 males and females were bred with fish of the same treatment but
different families producing F1 offspring. Behavior in the novel tank test at
6months revealed that males with EE2-exposed parents had significantly longer
latency to the upper half of the tank than control males, while no EE2 effects
were observed in females. Also in F2, obtained from F1 as above, males in the EE2
group had longer latency time compared to control males, with no differences due
to EE2-exposure of F0 observed in females. In the scototaxis (light/dark
preference) test, latency to first transition to black compartment and total
transitions to black were significantly altered in females due to EE2 exposure of
F0 while the total time in black was higher in males with EE2-exposed F0 compared
with controls. The increased anxiety in the F2 generation demonstrates a
transgenerational anxiety phenotype and shows that non-reproductive behavior can
be transgenerationally modified by estrogens in fish.
PMID- 26431612
TI - Implications of monotreme and marsupial chromosome evolution on sex determination
and differentiation.
AB - Studies of chromosomes from monotremes and marsupials endemic to Australasia have
provided important insight into the evolution of their genomes as well as
uncovering fundamental differences in their sex determination/differentiation
pathways. Great advances have been made this century into solving the mystery of
the complicated sex chromosome system in monotremes. Monotremes possess multiple
different X and Y chromosomes and a candidate sex determining gene has been
identified. Even greater advancements have been made for marsupials, with
reconstruction of the ancestral karyotype enabling the evolutionary history of
marsupial chromosomes to be determined. Furthermore, the study of sex chromosomes
in intersex marsupials has afforded insight into differences in the sexual
differentiation pathway between marsupials and eutherians, together with
experiments showing the insensitivity of the mammary glands, pouch and scrotum to
exogenous hormones, led to the hypothesis that there is a gene (or genes) on the
X chromosome responsible for the development of either pouch or scrotum. This
review highlights the major advancements made towards understanding chromosome
evolution and how this has impacted on our understanding of sex determination and
differentiation in these interesting mammals.
PMID- 26431613
TI - Endogenous control of sexual size dimorphism: Gonadal androgens have neither
direct nor indirect effect on male growth in a Madagascar ground gecko (Paroedura
picta).
AB - Changes in the effect of gonadal androgens on male growth are considered as a
possible mechanism allowing shifts in magnitude and even direction of sexual size
dimorphism in vertebrates, particularly squamate reptiles. Positive effects of
gonadal androgens on male growth were found in several male-larger species of
lizards. Contrastingly, we document that in the male-larger Madagascar ground
gecko (Paroedura picta) gonadal androgens do not affect male growth under
constant thermal conditions. However, the absence of a thermal gradient might
prevent the potential indirect effect of gonadal androgens on growth via the
influence of circulating hormones on an individual's thermoregulation and hence
metabolic rate. In order to study this, we monitored the growth and body
temperature of socially isolated sham-operated and castrated males of the same
species in a thermal gradient. We also compared the oxygen consumption and
activity between the treatment groups in the open field to test the effect of
gonadal hormones on these traits potentially affecting growth. Even under a
thermal gradient we found no effect of gonadal androgens on growth rate or final
body dimensions. Castration also did not significantly affect oxygen consumption
or activity in the open field test. Together with our previous findings, we can
exclude both the direct effect of male gonadal androgens on the ontogeny of
sexual size dimorphism via the influence on the growth axis, and the indirect
influence of gonadal androgens acting on the ontogeny of SSD through the effect
on thermoregulation, metabolic rate and activity.
PMID- 26431614
TI - Non-hazardous pesticide concentrations in surface waters: An integrated approach
simulating application thresholds and resulting farm income effects.
AB - Pesticide application rates are high and increasing in upland agricultural
systems in Thailand producing vegetables, fruits and ornamental crops, leading to
the pollution of stream water with pesticide residues. The objective of this
study was to determine the maximum per hectare application rates of two widely
used pesticides that would achieve non-hazardous pesticide concentrations in the
stream water and to evaluate how farm household incomes would be affected if
farmers complied with these restricted application rates. For this purpose we
perform an integrated modeling approach of a hydrological solute transport model
(the Soil and Water Assessment Tool, SWAT) and an agent-based farm decision model
(Mathematical Programming-based Multi-Agent Systems, MPMAS). SWAT was used to
simulate the pesticide fate and behavior. The model was calibrated to a 77 km(2)
watershed in northern Thailand. The results show that to stay under a pre-defined
eco-toxicological threshold, the current average application of chlorothalonil
(0.80 kg/ha) and cypermethrin (0.53 kg/ha) would have to be reduced by 80% and
99%, respectively. The income effect of such reductions was simulated using
MPMAS. The results suggest that if farm households complied with the application
thresholds then their income would reduce by 17.3% in the case of chlorothalonil
and by 38.3% in the case of cypermethrin. Less drastic income effects can be
expected if methods of integrated pest management were more widely available. The
novelty of this study is to combine two models from distinctive disciplines to
evaluate pesticide reduction scenarios based on real-world data from a single
study site.
PMID- 26431615
TI - Patient assessment in polytrauma: current trends rely on multiple parameters to
improve the prediction of complications and mortality.
PMID- 26431616
TI - Spoilt for choice: A critical review on the chemical and biological assessment of
current wastewater treatment technologies.
AB - The knowledge we have gained in recent years on the presence and effects of
compounds discharged by wastewater treatment plants (WWTPs) brings us to a point
where we must question the appropriateness of current water quality evaluation
methodologies. An increasing number of anthropogenic chemicals is detected in
treated wastewater and there is increasing evidence of adverse environmental
effects related to WWTP discharges. It has thus become clear that new strategies
are needed to assess overall quality of conventional and advanced treated
wastewaters. There is an urgent need for multidisciplinary approaches combining
expertise from engineering, analytical and environmental chemistry,
(eco)toxicology, and microbiology. This review summarizes the current approaches
used to assess treated wastewater quality from the chemical and ecotoxicological
perspective. Discussed chemical approaches include target, non-target and suspect
analysis, sum parameters, identification and monitoring of transformation
products, computational modeling as well as effect directed analysis and toxicity
identification evaluation. The discussed ecotoxicological methodologies encompass
in vitro testing (cytotoxicity, genotoxicity, mutagenicity, endocrine disruption,
adaptive stress response activation, toxicogenomics) and in vivo tests (single
and multi species, biomonitoring). We critically discuss the benefits and
limitations of the different methodologies reviewed. Additionally, we provide an
overview of the current state of research regarding the chemical and
ecotoxicological evaluation of conventional as well as the most widely used
advanced wastewater treatment technologies, i.e., ozonation, advanced oxidation
processes, chlorination, activated carbon, and membrane filtration. In
particular, possible directions for future research activities in this area are
provided.
PMID- 26431617
TI - Open your eyes and you will see. Changes in "eyes-open" versus "eyes-closed"
small-world properties of EEG functional connectivity in amnesic mild cognitive
impairment.
PMID- 26431618
TI - Somatosensory-evoked potential modulation by quadripulse transcranial magnetic
stimulation in patients with benign myoclonus epilepsy.
AB - OBJECTIVE: In patients with benign myoclonus epilepsy (ME), giant sensory-evoked
potential (SEP) reflects the hyperexcitability of the sensory cortex. The aim of
this study was to compare the effect of quadripulse transcranial magnetic
stimulation (QPS) on the median nerve SEP between ME patients and healthy
subjects. METHODS: Ten healthy volunteers and six ME patients with giant SEP
participated in this study. QPSs at interpulse intervals (IPIs) of 5, 30, 50,
100, 500 and 1250 ms were applied over the left primary motor cortex (M1) for 30
min. The peak-to-peak amplitudes of N20 to P25 (N20-P25) and P25 to N33 (P25-N33)
components were measured at the left somatosensory cortex. RESULTS: In healthy
participants, the P25-N33 was bidirectionally modulated by QPS over M1, following
the Bienenstock-Cooper-Munro (BCM) theory. The N20-P25 was not affected by any
QPSs. In ME patients, the giant P25-N33 was potentiated after any QPSs.
Furthermore, the N20-P25 was also potentiated after QPS at IPIs of 5, 30, 50 100
or 500 ms. CONCLUSIONS: In ME patients, the cascade for long-term depression-like
effects may be impaired. SIGNIFICANCE: The giant SEP was furthermore enhanced by
QPS.
PMID- 26431619
TI - [Antenatal palliative plan following diagnosis of fetal lethal condition: Rennes
Teaching Hospital experience].
AB - OBJECTIVES: To study the pregnancies followed at Rennes University Hospital from
2006 to 2012, after prenatal diagnosis of lethal fetal condition and prenatal
project of palliative care at birth consisting of comfort care emphasizing parent
child encounters and bonding. MATERIAL AND METHODS: Retrospective study of 20
pregnancies with diagnosis of lethal fetal condition where parents accepted
antenatally the proposal or sought for palliative care at birth. RESULTS:
Diagnosis was made at a median age of 20 weeks gestation (12-33). Birth occurred
at 37.4 WG, 6 caesarean sections were performed for maternal conditions. Six
cases of hypoplastic left heart syndrome (HLHS) share common characteristics:
good Apgar score, prolonged survival (26hours to 159days) transfer to neonatology
ward (6) or later at home (4). In four multiple pregnancies, the choice of SP
mainly contributed to protect healthy twins during pregnancy. In birth room,
there was no need for invasive procedure or drugs. Death: one occurred during
labor, 8 in birth room before H2, others in neonatal ward before d4 (excluding
HLHS). CONCLUSION: These data will enable better antenatal preparation of both
teams and parents. Lifetime, however short, allowed parents to meet with their
child alive this permitting collection of memory traces and bonding.
PMID- 26431620
TI - [Customized and non-customized French intrauterine growth curves. II - Comparison
with existing curves and benefits of customization].
AB - OBJECTIVES: Our aim is to compare the new French EPOPe intrauterine growth
curves, developed to address the guidelines 2013 of the French College of
Obstetricians and Gynecologists, with reference curves currently used in France,
and to evaluate the consequences of their adjustment for fetal sex and maternal
characteristics. POPULATION AND METHODS: Eight intrauterine and birthweight
curves, used in France were compared to the EPOPe curves using data from the
French Perinatal Survey 2010. The influence of adjustment on the rate of SGA
births and the characteristics of these births was analysed. RESULTS: Due to
their birthweight values and distribution, the selected intrauterine curves are
less suitable for births in France than the new curves. Birthweight curves led to
low rates of SGA births from 4.3 to 8.5% compared to 10.0% with the EPOPe curves.
The adjustment for maternal and fetal characteristics avoids the over
representation of girls among SGA births, and reclassifies 4% of births. Among
births reclassified as SGA, the frequency of medical and obstetrical risk factors
for growth restriction, smoking (>=10 cigarettes/day), and neonatal transfer is
higher than among non-SGA births (P<0.01). CONCLUSION: The EPOPe curves are more
suitable for French births than currently used curves, and their adjustment
improves the identification of mothers and babies at risk of growth restriction
and poor perinatal outcomes.
PMID- 26431621
TI - Effects of angiotensin II on leptin and downstream leptin signaling in the
carotid body during acute intermittent hypoxia.
AB - Angiotensin II (ANG II) is known to promote leptin production and secretion.
Although ANG II type 1 receptors (AT1Rs) and leptin are expressed within the
carotid body, it is not known whether AT1R and leptin are co-expressed in the
same glomus cells nor if these peptides are affected within the carotid body by
intermittent hypoxia (IH). This study was done to investigate whether ANG II
modulated leptin signaling in the carotid body during IH. Rats were treated with
captopril (Capt) or the AT1R blocker losartan (Los) in the drinking water for
3days prior to being exposed to IH (8h) or normoxia (8h). IH induced increases in
plasma ANG II and leptin compared to normoxic controls. Capt treatment abolished
the plasma leptin changes to IH, whereas Los treatment had no effect on the IH
induced increase in plasma leptin. Additionally, carotid body glomus cells
containing both leptin and the long form of the leptin receptor (OB-Rb) were
found to co-express AT1R protein, and IH increased the expression of only AT1R
protein within the carotid body in both Capt- and non-Capt-treated animals. On
the other hand, Los treatment did not modify AT1R protein expression to IH.
Additionally, Capt and Los treatment eliminated the elevated carotid body leptin
protein expression, and the changes in phosphorylated signal transducer and
activator of transcription three protein, the short form of the leptin receptor
(OB-R100), suppressor of cytokine signaling 3, and phosphorylated extracellular
signal-regulated kinase 1/2 protein expression induced by IH. However, Capt
elevated the expression of OB-Rb protein, whereas Los abolished the changes in OB
Rb protein to IH. These findings, taken together with the previous observation
that ANG II modifies carotid body chemosensitivity, suggest that the increased
circulating levels of ANG II and leptin induced by IH act at the carotid body to
alter leptin signaling within the carotid body which in turn may influence
chemoreceptor function.
PMID- 26431622
TI - The effect of WIN 55,212-2 suggests a cannabinoid-sensitive component in the
early toxicity induced by organic acids accumulating in glutaric acidemia type I
and in related disorders of propionate metabolism in rat brain synaptosomes.
AB - Several physiological processes in the CNS are regulated by the endocannabinoid
system (ECS). Cannabinoid receptors (CBr) and CBr agonists have been involved in
the modulation of the N-methyl-D-aspartate receptor (NMDAr) activation. Glutaric
(GA), 3-hydroxyglutaric (3-OHGA), methylmalonic (MMA) and propionic (PA) acids
are endogenous metabolites produced and accumulated in the brain of children
affected by severe organic acidemias (OAs) with neurodegeneration. Oxidative
stress and excitotoxicity have been involved in the toxic pattern exerted by
these organic acids. Studying the early pattern of toxicity exerted by these
metabolites is crucial to explain the extent of damage that they can produce in
the brain. Herein, we investigated the effects of the synthetic CBr agonist WIN
55,212-2 (WIN) on early markers of GA-, 3-OHGA-, MMA- and PA-induced toxicity in
brain synaptosomes from adult (90-day-old) and adolescent (30-day-old) rats. As
pre-treatment, WIN exerted protective effects on the GA- and MMA-induced
mitochondrial dysfunction, and prevented the reactive oxygen species (ROS)
formation and lipid peroxidation induced by all metabolites. Our findings support
a protective and modulatory role of cannabinoids in the early toxic events
elicited by toxic metabolites involved in OAs.
PMID- 26431623
TI - Reduced connectivity and inter-hemispheric symmetry of the sensory system in a
rat model of vulnerability to developing depression.
AB - Defining the markers corresponding to a high risk of developing depression in
humans would have major clinical significance; however, few studies have been
conducted since they are not only complex but also require homogeneous groups.
This study compared congenital learned helpless (cLH) rats, selectively bred for
high stress sensitivity and learned helplessness (LH) behavior, to congenital non
learned helpless (cNLH) rats that were bred for resistance to uncontrollable
stress. Naive cLH rats show some depression-like behavior but full LH behavior
need additional stress, making this model ideal for studying vulnerability to
depression. Resting-state functional connectivity obtained from seed correlation
analysis was calculated for multiple regions that were selected by anatomy AND by
a data-driven approach, independently. Significance was determined by t-statistic
AND by permutation analysis, independently. A significant reduction in functional
connectivity was observed by both analyses in the cLH rats in the sensory, motor,
cingulate, infralimbic, accumbens and the raphe nucleus. These reductions
corresponded primarily to reduced inter-hemispheric connectivity. The main
reduction however was in the sensory system. It is argued that reduced
connectivity and inter-hemispheric connectivity of the sensory system reflects an
internal convergence state which may precede other depressive symptomatology and
therefore could be used as markers for vulnerability to the development of
depression.
PMID- 26431625
TI - Adherence to Guidelines in Adult Patients with Traumatic Brain Injury: A Living
Systematic Review.
AB - Guidelines aim to improve the quality of medical care and reduce treatment
variation. The extent to which guidelines are adhered to in the field of
traumatic brain injury (TBI) is unknown. The objectives of this systematic review
were to (1) quantify adherence to guidelines in adult patients with TBI, (2)
examine factors influencing adherence, and (3) study associations of adherence to
clinical guidelines and outcome. We searched EMBASE, MEDLINE, Cochrane Central,
PubMed, Web of Science, PsycINFO, SCOPUS, CINAHL, and grey literature in October
2014. We included studies of evidence-based (inter)national guidelines that
examined the acute treatment of adult patients with TBI. Methodological quality
was assessed using the Research Triangle Institute item bank and Quality in
Prognostic Studies Risk of Bias Assessment Instrument. Twenty-two retrospective
and prospective observational cohort studies, reported in 25 publications, were
included, describing adherence to 13 guideline recommendations. Guideline
adherence varied considerably between studies (range 18-100%) and was higher in
guideline recommendations based on strong evidence compared with those based on
lower evidence, and lower in recommendations of relatively more invasive
procedures such as craniotomy. A number of patient-related factors, including
age, Glasgow Coma Scale, and intracranial pathology, were associated with greater
guideline adherence. Guideline adherence to Brain Trauma Foundation guidelines
seemed to be associated with lower mortality. Guideline adherence in TBI is
suboptimal, and wide variation exists between studies. Guideline adherence may be
improved through the development of strong evidence for guidelines. Further
research specifying hospital and management characteristics that explain
variation in guideline adherence is warranted.
PMID- 26431624
TI - Progression and recovery of Parkinsonism in a chronic progressive MPTP-induction
model in the marmoset without persistent molecular and cellular damage.
AB - Chronic exposure to low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
in marmoset monkeys was used to model the prodromal stage of Parkinson's disease
(PD), and to investigate mechanisms underlying disease progression and recovery.
Marmosets were subcutaneously injected with MPTP for a period of 12weeks,
0.5mg/kg once per week, and clinical signs of Parkinsonism, motor- and non-motor
behaviors were recorded before, during and after exposure. In addition,
postmortem immunohistochemistry and proteomics analysis were performed. MPTP
induced parkinsonian clinical symptoms increased in severity during exposure, and
recovered after MPTP administration was ended. Postmortem analyses, after the
recovery period, revealed no alteration of the number and sizes of tyrosine
hydroxylase (TH)-positive dopamine (DA) neurons in the substantia nigra. Also
levels of TH in putamen and caudate nucleus were unaltered, no differences were
observed in DA, serotonin or nor-adrenalin levels in the caudate nucleus, and
proteomics analysis revealed no global changes in protein expression in these
brain areas between treatment groups. Our findings indicate that parkinsonian
symptoms can occur without detectable damage at the cellular or molecular level.
Moreover, we show that parkinsonian symptoms may be reversible when diagnosed and
treated early.
PMID- 26431626
TI - Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation:
Risk Factors and Stratification, Prophylaxis, and Treatment.
AB - Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction
syndrome (SOS), can develop in a subset of patients, primarily after
myeloablative hematopoietic stem cell transplantation, but it also may occur
after reduced-intensity conditioning. Severe VOD/SOS, typically characterized by
multiorgan failure, has been associated with a mortality rate greater than 80%.
Therefore, an accurate and prompt diagnosis of VOD/SOS is essential for early
initiation of appropriate therapy to improve clinical outcomes. Moreover, some
studies have support the use of prophylaxis for patients who are at high risk of
developing VOD/SOS. This review summarizes risk factors associated with
development of VOD/SOS, including pretransplantation patient characteristics and
factors related to stem cell transplantation, that can facilitate patient
stratification according to risk. The incidence of VOD/SOS, clinical features,
and diagnostic criteria are reviewed. Data on emerging treatment strategies for
patients with VOD/SOS are discussed in the context of recent treatment
guidelines. Additionally, options for prophylaxis in individuals who are at
increased risk are presented. Although historically only those patients with
moderate to severe VOD/SOS have been treated, early therapy and prophylaxis may
be appropriate for many patients and may have the potential to improve patients'
outcomes and survival, including for those with nonsevere disease.
PMID- 26431627
TI - Reply to "Pharmacokinetic and Analytical Issues in Busulfan Area Under the Curve
Estimation and Simulation".
PMID- 26431628
TI - Graft-versus-Host Disease-Associated Vulvovaginal Symptoms after Bone Marrow
Transplantation.
AB - We conducted a retrospective review to assess the prevalence of graft-versus-host
disease (GVHD)-associated gynecologic conditions among bone marrow
transplantation (BMT) patients at City of Hope Medical Center. We calculated the
associations among the estimated risks of various gynecologic complications,
including vaginal stenosis, by performing chi-square tests and t-test statistics.
Between 2010 and 2014, 180 patients were referred to the gynecologic clinic after
their BMT. One hundred twenty-four patients (69%) had GVHD; among these patients,
51 (41%) experienced dyspareunia and 43 (35%) had vaginal stenosis. GVHD patients
were significantly more likely to have vaginal stenosis (P < .0001), more likely
to have used a vaginal dilator (P = .0008), and less likely to have urinary
incontinence (UI) than those without GVHD (P < .001). There was no difference in
developing pelvic organ prolapse (POP) in patients with or without GVHD (P =
.4373). GVHD was a common complication after allogenic BMT. Patients with BMT
were more likely to have vulvovaginal symptoms, such as dyspareunia and pelvic
pain. Patients with GVHD are at high risk for vaginal stenosis requiring the use
of a vaginal dilator. However, they are at low risk for developing UI and POP.
PMID- 26431629
TI - Pharmacokinetic and Analytical Issues in Busulfan Area Under the Curve Estimation
and Simulation.
PMID- 26431630
TI - Impact of Allele-Level HLA Mismatch on Outcomes in Recipients of Double Umbilical
Cord Blood Transplantation.
AB - The impact of allele-level HLA mismatch is uncertain in recipients of double
umbilical cord blood (UCB) transplantation. We report a single-center
retrospective study of the clinical effect of using allele-level HLA mismatch HLA
A, -B, -C, -DRB1, and -DQB1 of the 2 UCB units. We studied 342 patients with
hematologic malignancy. Donor-recipient pairs were grouped according to the
number of matched HLA alleles, with 32 matched at 9-10/10, 202 at 6-8/10, and 108
at 2-5/10 alleles. The incidence of hematopoietic recovery, acute and chronic
graft-versus-host disease, and nonrelapse mortality and treatment failure was
similar between groups. In an exploratory analysis of 174 patients with acute
leukemia, after adjusting for length of first remission and cytogenetic risk
group, a 2-5/10 HLA match was associated with lower risk of relapse and treatment
failure. These data indicate that a high degree of allele-level HLA mismatch does
not adversely affect transplant outcomes and may be associated with reduced
relapse risk in patients with acute leukemia.
PMID- 26431631
TI - The Japanese diet from 1975 delays senescence and prolongs life span in SAMP8
mice.
AB - OBJECTIVE: Life expectancy in Japan is high, suggesting that the Japanese diet,
Nihon shoku (Japanese food), has significant health benefits. However, these
benefits have been called into question over the past 50 y, during which time the
Japanese diet has become increasingly Westernized. The aim of the present study
was to focus on senescence delay and to examine the effects of Japanese diets
from different years to identify which Japanese diet is most effective in
enhancing life expectancy and delaying senescence. METHODS: Weekly menus from the
years 1960, 1975, 1990, and 2005 were reproduced based on the National Health and
Nutrition Survey in Japan and prepared as powdered foods. The senescence
accelerated mouse prone 8 (SAMP8) mice were fed standard laboratory chow
supplemented with a 30% mix of Japanese meals from various years ad libitum
throughout their lifetime. Additionally, the control group was given standard
laboratory chow only, to examine the development of mice reared under standard
conditions. RESULTS: In the group that ingested the traditional 1975 Japanese
diet, life span was prolonged, senescence was delayed, and learning and memory
capacities were maintained compared with the group fed the 2005 Japanese diet.
The life span of the group that ingested the 1990 Japanese diet showed a tendency
to be longer than SAMP8 mice fed the 2005 diet. CONCLUSION: The results of the
present study suggested that the traditional Japanese diet is more effective in
enhancing life expectancy and delaying senescence than the current Japanese diet.
PMID- 26431632
TI - Harnessing the microRNA pathway for cardiac regeneration.
AB - Mounting evidence over the last few years has indicated that the rate of
cardiomyocyte proliferation, and thus the extent of cardiac renewal, is under the
control of the microRNA network. Several microRNAs (e.g. miR-1) regulate
expansion of the cardiomyocyte pool and its terminal differentiation during the
embryonic life; some not only promote cardiomyocyte proliferation but also their
de-differentiation towards an embryonic cell phenotype (e.g. the miR-302/367
cluster); a few others are involved in the repression of cardiomyocyte
proliferation occurring suddenly after birth (e.g. the miR-15 family); others
again are not physiologically involved in the regulation of cardiomyocyte
turnover, but nevertheless are able to promote cardiomyocyte proliferation and
cardiac regeneration when delivered exogenously (e.g. miR-199a-3p). With a few
exceptions, the molecular mechanisms underlying the pro-proliferative effect of
these microRNAs, most of which appear to act at the level of already
differentiated cardiomyocytes, remain to be thoroughly elucidated. The
possibility of harnessing the miRNA network to achieve cardiac regeneration paves
the way to exciting therapeutic applications. This could be achieved by either
administering miRNA mimics or inhibitors, or transducing the heart with viral
vectors expressing miRNA-encoding genes.
PMID- 26431633
TI - Laparoscopic sleeve gastrectomy in children and adolescents with Prader-Willi
syndrome: a matched-control study.
AB - BACKGROUND: Obesity is a leading cause of mortality and morbidity in Prader-Willi
syndrome (PWS). OBJECTIVES: To study weight loss and growth after laparoscopic
sleeve gastrectomy (LSG) in pediatric patients with PWS compared with those
without the syndrome. SETTING: Academic center with a standardized care pathway
for pediatric bariatric surgery as a part of a prospective clinical outcome study
on children and adolescents undergoing weight loss surgery. METHODS: Clinical
data of all PWS patients who underwent LSG were abstracted from our prospective
database, which included all pediatric patients who underwent bariatric surgery.
These data were then compared with a 1:3 non-PWS group matched for age, gender,
and body mass index (BMI). Data for up to 5 years follow-up were analyzed.
RESULTS: The 24 PWS patients (mean age 10.7; 6<8 yr old, range 4.9-18) had a
preoperative BMI of 46.2 +/- 12.2 kg/m(2). All PWS patients had obstructive sleep
apnea (OSA), 62% had dyslipidemia, 43% had hypertension, and 29% had diabetes
mellitus. BMI change at the first, second, third, fourth, and fifth annual visits
was -14.7 (n = 22 patients), -15.0 (n = 18), 12.2 (n = 13), -12.7 (n = 11), and
10.7 (n = 7), respectively, in the PWS group, whereas the non-PWS group had a BMI
change of -15.9 (n = 67), -18.0 (n = 50), -18.4 (n = 47), -18.9 (n = 26), and
19.0 (n = 20), respectively. No significant difference was observed in
postoperative BMI change (P = .2-.7) or growth (postoperative height z-score P
value at each annual visit = .2-.8); 95% of co-morbidities in both groups were in
remission or improved, with no significant difference in the rate of co-morbidity
resolution after surgery (P = .73). One PWS patient was readmitted 5 years after
surgery with recurrence of OSA and heart failure. No other readmissions occurred,
and there were no reoperations, postoperative leaks, or other complications. No
mortality or major morbidity was observed during the 5 years of follow-up. Among
the PWS patients who reached their follow-up visit time points the total follow
up rate was 94.1%, whereas in the non-PWS group it was 97%. All patients who
missed a follow-up visit were subsequently seen in future follow-ups, and no
patient was lost to follow-up in either group. CONCLUSIONS: PWS children and
adolescents underwent effective weight loss and resolution of co-morbidities
after LSG, without mortality, significant morbidity, or slowing of growth. LSG
should be offered to obese PWS patients with heightened mortality particularly
because no other effective alternative therapy is available.
PMID- 26431634
TI - The fossil record of ecdysis, and trends in the moulting behaviour of trilobites.
AB - Ecdysis, the process of moulting an exoskeleton, is one of the key characters
uniting arthropods, nematodes and a number of smaller phyla into Ecdysozoa. The
arthropod fossil record, particularly trilobites, eurypterids and decapod
crustaceans, yields information on moulting, although the current focus is
predominantly descriptive and lacks a broader evolutionary perspective. We here
review literature on the fossil record of ecdysis, synthesising research on the
behaviour, evolutionary trends, and phylogenetic significance of moulting
throughout the Phanerozoic. Approaches vary widely between taxonomic groups, but
an overall theme uniting these works suggests that identifying moults in the
palaeontological record must take into account the morphology, taphonomy and
depositional environment of fossils. We also quantitatively analyse trends in
trilobite ecdysis based on a newly generated database of published incidences of
moulting behaviour. This preliminary work reveals significant taxonomic and
temporal signal in the trilobite moulting fossil record, with free cheek moulting
being prevalent across all Orders and throughout the Phanerozoic, and peaks of
cephalic moulting in Phacopida during the Ordovician and rostral plate moulting
in Redlichiida during the Cambrian. This study and a review of the literature
suggest that it is feasible to extract large-scale evolutionary information from
the fossil record of moulting.
PMID- 26431635
TI - The branchiostegal lung of Uca vocans (Decapoda: Ocypodidae): Unreported
complexity revealed by corrosion casting and MicroCT techniques.
AB - The study of adaptation to terrestrial life in crabs poses several physiological
questions. One of the major challenges the crabs have to face is respiration of
air: most of the time, gills are unsuitable to perform oxygen exchange out of the
water. Fiddler crabs, like other representatives of the Ocypodidae, have
developed an additional mechanism of respiration by improving the circulation
that lines the branchiostegal chamber, thus developing a branchiostegal lung. In
the present study we describe the hitherto unreported complex morphology of the
branchiostegal lung of the fiddler crab Uca vocans by means of corrosion casting
techniques and 3D reconstruction. This complexity leads us to reconsider the
degree of terrestriality of U. vocans and its evolutionary pathway towards land.
PMID- 26431636
TI - The morphology of the eggs of three species of Zoraptera (Insecta).
AB - The egg structure of Zorotypus magnicaudelli, Zorotypus hubbardi and Zorotypus
impolitus was examined and described in detail. Major characteristics of
zorapteran eggs previously reported were confirmed in these species, with the
partial exception of Z. impolitus: 1) a pair of micropyles at the equator of the
egg's ventral side, 2) a honeycomb pattern on the egg surface, 3) a two-layered
chorion, 4) micropylar canals running laterally, 5) a flap covering the inner
opening of the micropylar canal and 6) no region specialized for hatching. These
features are probably part of the groundplan of the order. Three groups (A-C) and
two subgroups (A1 and A2) of Zoraptera can be distinguished based on characters
of the reproductive apparatus including eggs. However, information for more
species is needed for a reliable interpretation of the complex and apparently
fast evolving character system. The egg of Z. impolitus presumably shows
apomorphic characteristics not occurring in other species, a chorion without
layered construction and polygonal surface compartments with different sculptures
on the dorsal and ventral sides of the egg. Another feature found in this
species, distinct enlargement of the micropyles, is also found in Z. hubbardi.
The increased micropylar size is likely correlated with the giant spermatozoa
produced by males of these two species. These two features combined with the
large size of the spermatheca are arguably a complex synapomorphy of Z. hubbardi
and Z. impolitus. The phylogenetic placement of Zoraptera is discussed based on
the egg structure. A clade of Zoraptera + Eukinolabia appears most plausible, but
the issue remains an open question.
PMID- 26431637
TI - The sperm pump of the hangingfly Bittacus planus Cheng (Mecoptera: Bittacidae).
AB - The males of antliophoran insects usually use a sperm pump to transfer liquid
sperm into the reproductive tract of the female. However, the fine structure of
the sperm pump and its ejaculatory mechanism has not been thoroughly clarified in
many groups of Mecoptera. In this paper, the structure of the sperm pump was
investigated in the hangingfly Bittacus planus Cheng, 1949 using light and
scanning electron microscopy. The sperm pump mainly consists of a piston fused
with a piston-carrying sclerite, a pumping chamber enclosed by the genital folds,
which comprises the posterior region of the ejaculatory sac, an ostial sclerite,
a phallobase, and other associated structures and muscles. The piston crown plays
a major role in the piston movement. The ostial sclerite serves as a discharge
valve and is controlled by two antagonistic muscles. No depressor muscles were
found attached to the piston. The sperm pumping activity is mainly controlled by
the combination of the levator of the piston and the retractor and protractor of
the ostial sclerite. The ejaculatory mechanism and phylogenetic significance are
briefly discussed based on the structure of the sperm pump.
PMID- 26431638
TI - Determination of death after circulatory arrest by intensive care physicians: A
survey of current practice in the Netherlands.
AB - PURPOSE: Determination of death is an essential part of donation after
circulatory death (DCD). We studied the current practices of determination of
death after circulatory arrest by intensive care physicians in the Netherlands,
the availability of guidelines, and the occurrence of the phenomenon of
autoresuscitation. METHODS: The Determination of Cardiac Death Practices in
Intensive Care Survey was sent to all intensive care physicians. RESULTS: Fifty
five percent of 568 Dutch intensive care physicians responded. Most respondents
learned death determination from clinical practice. The most commonly used tests
for death determination were flat arterial line tracing, flat electrocardiogram
(standard 3-lead electrocardiogram), and fixed and dilated pupils. Rarely used
tests were absence pulse by echo Doppler, absent blood pressure by noninvasive
monitoring, and unresponsiveness to painful stimulus. No diagnostic test or
procedure was uniformly performed, but 80% of respondents perceived a need for
standardization of death determination. Autoresuscitation was witnessed by 37%,
after withdrawal of treatment or after unsuccessful resuscitation. CONCLUSIONS:
Extensive variability in the practice of determining death after circulatory
arrest exists, and a need for guidelines and standardization, especially if organ
donation follows death, is reported. Autoresuscitation is reported; this
observation requires attention in further prospective observational studies.
PMID- 26431639
TI - Reactive transport of uranium in fractured crystalline rock: Upscaling in time
and distance.
AB - Batch adsorption and breakthrough column experiments were conducted to evaluate
uranium transport through altered material that fills fractures in a granite rock
system at the Grimsel Test Site in Switzerland at pH 6.9 and 7.9. The role of
adsorption and desorption kinetics was evaluated with reactive transport modeling
by comparing one-, two-, and three-site models. Emphasis was placed on describing
long desorption tails that are important for upscaling in time and distance. The
effect of increasing pH in injection solutions was also evaluated. For pH 6.9, a
three-site model with forward rate constants between 0.07 and 0.8 ml g(-1) h(-1),
reverse rate constants between 0.001 and 0.06 h(-1), and site densities of 1.3,
0.104, and 0.026 MUmol g(-1) for 'weak/fast', 'strong/slow', and 'very
strong/very slow' sites provided the best fits. For pH 7.9, a three-site model
with forward rate constants between 0.05 and 0.8 mL g(-1) h(-1), reverse rate
constants between 0.001 and 0.6 h(-1), and site densities of 1.3, 0.039, and
0.013 MUmol g(-1) for a 'weak/fast', 'strong/slow', and 'very strong/very slow'
sites provided the best fits. Column retardation coefficients (Rd) were 80 for pH
6.9 and 10.3 for pH 7.9. Model parameters determined from the batch and column
experiments were used in 50 year large-scale simulations for continuous and pulse
injections and indicated that a three-site model is necessary at pH 6.9, although
a Kd-type equilibrium partition model with one-site was adequate for large scale
predictions at pH 7.9. Batch experiments were useful for predicting early
breakthrough times in the columns while column experiments helped differentiate
the relative importance of sorption sites and desorption rate constants on
transport.
PMID- 26431640
TI - Carbon storage potential by four macrophytes as affected by planting diversity in
a created wetland.
AB - Wetland creation has become a commonplace method for mitigating the loss of
natural wetlands. Often mitigation projects fail to restore ecosystem services of
the impacted natural wetlands. One of the key ecosystem services of newly created
wetlands is carbon accumulation/sequestration, but little is known about how
planting diversity (PD) affects the ability of herbaceous wetland plants to store
carbon in newly created wetlands. Most mitigation projects involve a planting
regime, but PD, which may be critical in establishing biologically diverse and
ecologically functioning wetlands, is seldom required. Using a set of 34
mesocosms (~1 m(2) each), we investigated the effects of planting diversity on
carbon storage potential of four native wetland plant species that are commonly
planted in created mitigation wetlands in Virginia - Carex vulpinoidea,
Eleocharis obtusa, Juncus effusus, and Mimulus ringens. The plants were grown
under the four distinctive PD treatments [i.e., monoculture (PD 1) through four
different species mixture (PD 4)]. Plant biomass was harvested after two growing
seasons and analyzed for tissue carbon content. Competition values (CV) were
calculated to understand how the PD treatment affected the competitive ability of
plants relative to their biomass production and thus carbon storage potentials.
Aboveground biomass ranged from 988 g/m(2) - 1515 g/m(2), being greatest in
monocultures, but only when compared to the most diverse mixture (p = 0.021).
However, carbon storage potential estimates per mesocosm ranged between 344 g
C/m(2) in the most diverse mesocosms (PD 4) to 610 g C/m(2) in monoculture ones
with no significant difference (p = 0.089). CV of E. obtusa and C. vulpinoidea
showed a declining trend when grown in the most diverse mixtures but J. effusus
and M. ringens displayed no difference across the PD gradient (p = 0.910). In
monocultures, both M. ringens, and J. effusus appeared to store carbon as biomass
more effectively than the other species, suggesting that the choice of plant
species may play an important role in facilitating the development of carbon
accumulation/storage in created wetlands. Plant community diversity provides many
ecosystem services (e.g., habitat and floristic quality) other than carbon
storage function. Thus, a further study is needed that will focus on
investigating how other design elements such as microtopography and hydrologic
connectivity may interact with PD in terms of enhancing the carbon storage
potential of newly created wetlands.
PMID- 26431641
TI - Stakeholder demands and corporate environmental coping strategies in China.
AB - This paper examines how stakeholder demand and compliance capacity jointly shape
corporate environmental coping strategies and subsequently environmental
protection practices. A four-dimensional classification of coping strategies
formalism, accommodation, referencing, and self-determination-is conceptualized.
Drawing on survey and interview data collected from manufacturing enterprises in
China between 2010 and 2012, the paper shows that compared with formalism and
accommodation, coping strategies of referencing and self-determination are
associated with stronger environmental protection practices. Enterprises adjust
their coping strategies by taking into account the constraints defined by both
their internal and external environments. The results also demonstrate the
potential synergetic effects of state and non-state stakeholders working together
in promoting better corporate environmental coping strategies and environmental
practices in China.
PMID- 26431642
TI - Evaluation of the stability of a nanoremediation strategy using barley plants.
AB - This study evaluated the effectiveness of nZVI in reducing the availability of
Cd, Cr or Zn in polluted soils. The influence of this nanoremediation process on
the development of barley plants as well as its impact on soil properties and the
stability of the metal immobilization afterwards were also evaluated in a
greenhouse experiment. The application of nZVI reduced the availability of these
metals in the soil, but the effectiveness of the immobilization and its stability
depended on the metal chemical characteristics. Cadmium distribution in soil
fractions showed an important change after the barley crop, favoring the
immobilization of Cd in RS fraction for both nZVI-treated and untreated soils.
The Cr immobilization was stable over the time studied and the doses of Cr were
lethal for the barley plants. In contrast, the decrease of Cr availability
reached after the nZVI treatment induced a reduction of soil phytotoxicity and an
improvement in the development of the plants, which were able to complete their
growing period. The Zn immobilization with nZVI was stable over time, but its
effectiveness was moderate, and the growth of barley plants was poorer than that
observed in the cases of Cd and Cr. Thus the best results of metal immobilization
with nZVI were obtained for Cr-polluted soils. There was no overall increase of
Fe in barley plants from nZVI-treated soils. In relation to the soil, no negative
effects on its physico-chemical properties were observed after the time exposure
with nZVI. Taking into account these results we can conclude that the use of nZVI
is a promising remediation strategy, and its effectiveness would be conditioned
to the soil properties and the bioavailable metal concentration.
PMID- 26431643
TI - Evolutionary genetic consequences of facultative sex and outcrossing.
AB - Explaining the selective forces that underlie different reproductive modes forms
a major part of evolution research. Many organisms are facultative sexuals, with
the ability to reproduce both sexually and asexually. Reduced sequencing costs
means it is now possible to start investigating genome sequences of a wider
number of these organisms in depth, but teasing apart the genetic forces
underlying the maintenance of facultative sexual reproduction remains a
challenge. An analogous problem exists when determining the genetic consequences
of a degree of outcrossing (and recombination) in otherwise self-fertilizing
organisms. Here, I provide an overview of existing research on the evolutionary
basis behind different reproductive modes, with a focus on explaining the
population genetic effects favouring low outcrossing rates in either partially
selfing or asexual species. I review the outcomes that both self-fertilization
and asexuality have on either purging deleterious mutations or fixing beneficial
alleles, and what empirical data exist to support these theories. In particular,
a greater application of mathematical models to genomic data has provided insight
into the numerous effects that transitions to self-fertilization from outcrossing
have on genetic architecture. Similar modelling approaches could be used to
determine the forces shaping genetic diversity of facultative sexual species.
Hence, a further unification of mathematical models with next-generation sequence
data will prove important in exploring the genetic influences on reproductive
system evolution.
PMID- 26431644
TI - Relationship inference from the genetic data on parents or offspring: A
comparative study.
AB - Relationship inference in a population is of interest for many areas of research
from anthropology to genetics. It is possible to directly infer the relationship
between the two individuals in a couple from their genetic data or to indirectly
infer it from the genetic data of one of their offspring. For this reason, one
can wonder if it is more advantageous to sample couples or single individuals to
study relationships of couples in a population. Indeed, sampling two individuals
is more informative than sampling one as we are looking at four haplotypes
instead of two, but it also doubles the cost of the study and is a more complex
sampling scheme. To answer this question, we performed simulations of 1000 trios
from 10 different relationships using real human haplotypes to have realistic
genome-wide genetic data. Then, we compared the genome sharing coefficients and
the relationship inference obtained from either a pair of individuals or one of
their offspring using both single-point and multi-point approaches. We observed
that for relationships closer than 1st cousin, pairs of individuals were more
informative than one of their offspring for relationship inference, and kinship
coefficients obtained from single-point methods gave more accurate or equivalent
genome sharing estimations. For more remote relationships, offspring were more
informative for relationship inference, and inbreeding coefficients obtained from
multi-point methods gave more accurate genome sharing estimations. In conclusion,
relationship inference on a parental pair or on one of their offspring provides
complementary information. When possible, sampling trios should be encouraged as
it could allow spanning a wider range of potential relationships.
PMID- 26431646
TI - Research on curative effect of traditional Chinese medicine treating low-grade
fever of children caused by respiratory system infection.
AB - This study aims to explore the curative effect of traditional Chinese medicine
treating low-grade fever of children caused by respiratory system infection.
Sixty children who suffered low-grade fever caused by respiratory system
infection were selected and divided into treatment group and control group
randomly, each with 30 cases. Control group was treated with conventional methods
including oxygen uptake, nebulization and anti-infection, etc, while treatment
group was given boil-free granules of traditional Chinese medicine besides the
treatment which control group received. Then clinical curative effect of two
groups was compared. Results showed that 28 cases (93.3%) were cured in treatment
group; while 21 cases (70.0%) were cured in control group. Compared with control
group, the treatment group showed up better treatment efficiency and the
difference between groups was of statistical significance (P<0.05). Comparison of
results of two groups suggested that, traditional Chinese medicine granules has
satisfactory curative effect in the treatment of low-grade fever of children
caused by respiratory system infection; characterized by short treatment cycle
and effective treatment effect, Chinese medicine granules in the combination with
oxygen atomization inhalation is proved to be able to efficiently remit symptoms
such as coughing, gasp and labored breathing, with outstanding curative effect in
the treatment of low-grade fever of children caused by respiratory system
infection, thus it is worthy of popularization and application clinically.
PMID- 26431645
TI - Activity-triggered tetrapartite neuron-glial interactions following peripheral
injury.
AB - Recent studies continue to support the proposition that non-neuronal components
of the nervous system, mainly glial cells and associated chemical mediators,
contribute to the development of neuronal hyperexcitability that underlies
persistent pain conditions. In the event of peripheral injury, enhanced or
abnormal nerve input is likely the most efficient way to activate simultaneously
central neurons and glia. Injury induces phenotypic changes in glia and triggers
signaling cascades that engage reciprocal interactions between presynaptic
terminals, postsynaptic neurons, microglia and astrocytes. While some responses
to peripheral injury may help the nervous system to adapt positively to counter
the disastrous effect of injury, the net effect often leads to long-lasting
sensitization of pain transmission pathways and chronic pain.
PMID- 26431647
TI - Effect of estrogen on recovering the injured nervous system.
AB - Estrogen plays an important role in the recovery of injured nervous system. This
study aims to discuss the effect of estrogen on glial cells in spinal cord and
apoptosis of neuron at different time points with a hope to lay theoretical basis
on treating acute spinal cord injury (SCI) in clinic. Totally 72 adult rats were
divided into a simple injury group and an estrogen group. Then several animal
models with SCI were prepared. The estrogen group was treated with intramuscular
injection of 100 ug/kg estrogen every day till the death of animal models, while
the simple injury group was treated with intramuscular injection of 0.5 mL saline
every day. Then these animals were put to death in the 1st d, 3rd d, 5th d, 8th
d, 14th d and 21st d after SCI respectively and tissue sections were prepared,
followed by B-cell lymphoma-2 (Bcl-2) detection, Terminal Deoxynucleotidyl
Transferase-mediated dUTP nick-end labeling (TUNEL) and detection of the cell
apoptosis in animal models after SCI. In the 14th d after the injury of spinal
cord nervous system, Gale grading and inclined plate maintenance tests were
carried out. In the 1st d after SCI, there was a higher expression of Bcl-2
protein in the SCI tissues. Bcl-2 protein reached the peak in the 3rd d after SCI
in the simple injured group, while the estrogen group reached the peak in the 8th
d. At that time, Bcl-2 protein was both expressed in nerve cells, and in glial
cells in a higher level. The expression began to decline in the 14th d after SCI,
and with only a little expression in the 21st d after SCI (p<0.05). TUNEL
detection results showed that, positive cells dominated by glial cells emerged in
simple injured group only 24th h later; they reached the peak after 3~8 days, and
then began to reduce. In the 21st d, positive cells still existed, and there was
less cell apoptosis after treated with estrogen (p<0.05). Two weeks after SCI,
Gale score and inclined plate maintenance rate were higher in the estrogen group
than in the simple injured group (p<0.01). Adverse effects that occurred in
injury group included blood dryness, necrosis, cyst cavity and cavity, while in
estrogen group, adverse effects included focal bleeding, hydropic degeneration of
neuron, disappearance of partial nissl bodies and neuraxial edema. All these
findings suggest that, estrogen used for treating SCI can effectively inhibit the
apoptosis of early nerve cells and glial cells in injured spinal cord nervous
system by improving the micro-circulation, enhancing the expression of Bcl-2
protein, removing the free radicals and inhibiting the antioxidation. Thus, it
can reduce the secondary SCI and promote the recovery of injured spinal cord
nervous functions.
PMID- 26431648
TI - Oxygen-driving and atomized mucosolvan inhalation combined with holistic nursing
in the treatment of children severe bronchial pneumonia.
AB - This paper aimed to discuss the method, effect and safety of oxygen-driving and
atomized Mucosolvan inhalation combined with holistic nursing in the treatment of
children severe bronchial pneumonia. Totally 90 children with severe bronchial
pneumonia who were treated in our hospital from March 2013 to November 2013 were
selected as the research objects. Based on randomized controlled principle, those
children were divided into control group, test group I and test group II
according to the time to enter the hospital, 30 in each group. Patients in
control group was given conventional therapy; test group I was given holistic
nursing combined with conventional therapy; test group II was given oxygen
driving and atomized Mucosolvan inhalation combined with holistic nursing on the
basis of conventional therapy. After test, the difference of main symptoms in
control group, test group I and II was of no statistical significance (P>0.05).
Test group II was found with the best curative effect, secondary was test group I
and control group was the last. It can be concluded that, oxygen-driving and
atomized Mucosolvan inhalation combined with holistic nursing has certain effect
in the treatment of children severe bronchial pneumonia and is better than
holistic nursing only.
PMID- 26431649
TI - Drug-induced skin toxicity and clinical nursing of VitK cream on colorectal
cancer patients.
AB - To discuss the impact of 0.1% vitamin K1 (VitK1) cream on cetuximab-induced skin
toxicity for colorectal cancer patients. 60 colorectal cancer patients with
cetuximab therapy after hospitalization, were divided into experimental group
(Ward A) and control group (Ward B) according to personnel sequential number,
with 30 cases in each group. Routine nursing was implemented on control group.
For experimental group, on the routine nursing basis, 0.1% VitK1 cream was
smeared on face, neck, chest, back and nail (toenail) edge with three times one
day at the application of cetuximab day. After cetuximab applied in 8 weeks, both
skin itch and dry skin for patients in experimental group were significantly
improved compared those in control group, showing statistically significant
difference (W=708.000, P=0.001: W=662. 500, P=0.000). 0.1% VitK1 cream was
conducive to improve both skin itch and dry skin symptoms in the cetuximab
induced skin toxicity for colorectal cancer patients.
PMID- 26431650
TI - Study on the clinical efficacy of Human Urinary Kalllikrein in the treatment of
acute cerebral infarction according to TOAST classification.
AB - To observe and evaluate the clinical efficacy of Human Urinary Kallikrein in the
treatment of acute cerebral infarction (ACT) according to TOAST (The Trial of Org
10172 in Acute Stroke Treatment) classification. In accordance with randomized
controlled trial, 110 patients with acute cerebral infarction were randomly
assigned to kallikrein treatment group (55 cases) and control group (55 cases).
TOAST classification and basic treatment were administrated on patients between
two groups respectively. 0.15 PNA unit of Human Urinary Kallikrein injection plus
100 mL saline in intravenous infusion was performed in the kallikrein group, with
once a day for 14 consecutive days. The National Institutes of Health Stroke
Scale (NIHSS) scores in two groups were analyzed before and after the treatment.
No difference was shown in the NIHSS scores before treatment among patients
between two groups (P>0.05). While after the treatment, the NIHSS scores in both
groups were reduced (P<0.05) and the NIHSS scores in the kallikrein treatment
group were less than those in control group (P<0.05). Moreover, after the
treatment, the NIHSS scores for large-artery atherosclerosis subtype (L) and
small-artery occlusion lacunar subtype (S) as two subtypes of TOAST
classification in the two groups were both reduced (P<0.05). After the treatment,
NIHSS scores for L subtype in the kallikrein treatment were less than those in
the control group (P<0.05). After the treatment, NIHSS scores for S subtype in
the kallikrein treatment were less than those in the control group, without
statistically significant difference. Comparisons on clinical efficacy indicated
differences on the S subtype between two groups (P<0.05). The standardization
effective rate was calculated, indicating 81.82% in the kallikrein treatment
group and 54.55% in the control group, respectively. In TOAST classification,
Human Urinary Kallikrein is able to remarkably improve the NIHSS scores for L
subtype and S subtype patients with acute cerebral infarction and help to enhance
the clinical efficacy.
PMID- 26431651
TI - Comparative studies on antioxidant activity and polyphenolic content of Lycium
barbarum L. and Lycium chinense Mill. leaves.
AB - The purpose of this research was to bring new data regarding the phenolic
composition and the antioxidant activity of L. barbarum L. and L. chinense Mill.
leaves. The determination of the main polyphenolic compounds was performed using
a HPLC-UV-MS method. The dominant compound found for both species was rutin, with
its highest amount registered in L. chinense (24141.90+/-21.3 MU/g plant
material) leaves. Among the flavonoidic aglycones, quercetin was found in both
samples, being quantified in a higher amount in L. chinense. In the antioxidant
assays, both extracts exhibited important antioxidant activities, as witnessed by
the three methods, both correlated with their total polyphenolic content.
PMID- 26431652
TI - Phytochemical and biological evaluation of Buddleja polystachya growing in Saudi
Arabia.
AB - Several Buddleja species were the target of phytochemical and biological studies;
however, nothing was reported concerning the chemistry of Buddleja polystachya
Fresen. growing in Saudi Arabia. Sixteen constituents were isolated from the
aerial parts of B. polystachya using various chromatographic techniques and were
identified by the help of different spectral techniques including 1D, 2D NMR and
mass spectrometry. Moreover, the different fractions were evaluated for their
anti-inflammatory and hypoglycemic activities. The isobenzofuranone derivative (4
hydroxy-7-methylisobenzofuranone) (4), has been isolated for the first time from
this natural source, B. polystachya, along with fifteen known compounds namely;
phenolic fatty acid ester, 1'(4-hydroxyphenyl) ethanol ester of docosanoic (1),
uvaol (2), sakuranetin (3), kumatakenin (5), cirsimaritin (6), 5-hydroxy-3,7,4'
trimethoxyflavone (7), oleanolic acid (8), herbacetin 3,7,8-trimethyl ether (9),
ursolic acid (10), verbascoside (11), linarin (12), luteolin 7-O-beta-D-glucoside
(13), luteolin 7-(6"-caffeoyl)-O-beta-D-glucopyranoside (14), luteolin (15), and
6-O-alpha-L-(4''-O-trans-cinnamoyl) rhamnopyranosylcatalpol (16). Regarding the
biological activities investigated, the ethyl acetate fraction showed the most
significant anti-inflammatory activity, followed by the n-butanol and the aqueous
fractions. As for the petroleum ether and dichloromethane fractions, their anti
inflammatory effects were moderate. The highest hypoglycemic activity was
possessed by the ethyl acetate fraction, followed by the dichloromethane fraction
and the n-butanol fraction showed the weakest activity.
PMID- 26431653
TI - Clinical curative effect observation of therapy of Chinese drug iontophoresis in
treatment of degenerative osteoarthropathy.
AB - Degenerative osteoarthropathy is a kind of arthrosis induced by various factors,
with main pathological feature of articular cartilage and syndesmophyte
formation. In recent years, its morbidity increases year by year and tend to
appear more among young people. Its curative effect has yet to be improved. This
paper mainly discussed the clinical curative effect of therapy of Chinese drug
iontophoresis in degenerative osteoarthropathy. A total of 296 cases of
degenerative osteoarthropathy was randomly divided into two groups (with no
consideration on gender): Chinese drug iontophoresis group: joint was treated by
therapy of Chinese drug iontophoresis and MTZ-F experiment; frequency
electrotherapy group: joint was only treated by medium frequency electrotherapy.
Two groups were both treated for 30 min for one time, 1 time for a day, total for
4 weeks. Result of the study found that, total effective rate of medium frequency
electrotherapy group was 74.3%, Chinese medicine iontophoresis group was 93.2%;
curative effect of Chinese medicine iontophoresis group was superior to
electrotherapy group. It indicates that, Chinese medicine iontophoresis has good
clinical effect in the treatment of osteoarthropathy and deserves to be
popularized and applied.
PMID- 26431654
TI - Effectiveness evaluation of cardiovascular drugs based on CYP2C9 target protein.
AB - This study is to discuss the effectiveness evaluation of cardiovascular drugs
based on CYP2C9 target protein. Multilevel fuzzy comprehensive evaluation method
was taken to evaluate the individualized medication effectiveness for
cardiovascular drug under the function of CYP2P9 target protein. Then, it was
established for the index system to affect drug efficacy and index weight was
settled. This index system was applied on the study of valsartan drugs to
evaluate the drug efficacy rate of sample. Results corresponded with the actual
drug treatment, and received better verification. The beneficial exploration was
performed for the effectiveness evaluation of individualized administration.
PMID- 26431655
TI - Report: Clinical characteristics and treatment experience report of severe
pulmonary infection after renal transplantation.
AB - This study was to discuss the clinical diagnosis and treatment features of severe
pulmonary infections after renal transplantation, in order to improve the cure
rate. Retrospective research was applied to analyze the 52 cases of patients with
serve pulmonary infection after renal transplantation in the department of organ
transplantation in People's Hospital of Zhengzhou from July, 2008 to December,
2013. The pathogens which caused the pulmonary infection after renal
transplantation were bacteria, virus, fungi, mycobacterium tuberculosis, combined
infection and unknown pathogens, and the rate were respectively 28.85%, 15.38%,
7.69%, 3.85%, 21.15% and 23.08%. In the 52 cases, there were 41 cases of patients
successfully survived, which was 78.85% and 11 cases died, which was 21.15%. The
mortality rate of combined infection and unknown pathogens infection was
significantly higher than that of single pathogen infection. Pulmonary infection
after renal transplantation was of rapid deteriorated progress and high mortality
rate. It was significant for patients to receive the comprehensive and integrated
treatment.
PMID- 26431656
TI - Study on antibacterial molecular drugs in Eucalyptus granlla wood extractives by
GC-MS.
AB - Eucalyptus granlla, which was one of dominant plantations in south China, was
deemed as the important wood bio resources. However, the small molecules of
Eucalyptus granlla wood weren't effectively reused. Thus the molecules of wood
extractives in Eucalyptus granlla were extracted and studied so as to further
utilize the resources. The result suggested that the optimal extraction time of
ethanol/methanol extraction, petroleum ether/acetic ether extraction, and
benzene/alcohol extraction were 5h, 7h and 4h, respectively. The wood extractives
included hexanedioic acid, bis (2-ethylhexyl) ester, 3,3,7,11
tetramethyltricyclo[5.4.0.0(4,11)] undecan-1-ol, squalene, etc. and wood
extractives of Eucalyptus granlla was suitable for extraction of 1,5-hexadien-3
yne and squalene.
PMID- 26431657
TI - Proteomic analysis of Corylus heterophylla fisch in Changbai Mountain by shotgun
approach.
AB - Total proteins of Changbai Mountain hazelnut were extracted and then enzymolysed
in solution. The mixture of peptides was separated on chromatograph and
identified by shotgun proteomics approach. The identified proteins were analyzed
by bioinformatics, 303 proteins were identified, of which 237 proteins (78.2%)
were mainly distributing in a range of 10-70 kDa and 85 proteins (28.1%) were
around pI 5-6. Based on the biological process cellular component and molecular
function, these proteins were classified by Gene Ontology, the results showed
that 183 proteins (73.8%) had catalytic activity (e.g. oxidoreductase, kinase,
peptidase, etc.), and 170 proteins (68.5%) had binding activity. The protein
profile provided a valuable basis for further research of hazelnut proteins and
opened up new research avenues related to the function of these proteins.
PMID- 26431658
TI - Comparison of clinical effect of dopamine and norepinephrine in the treatment of
septic shock.
AB - This study aims to compare the clinical effect of dopamine and nor epinephrine in
the treatment of septic shock. Fifty cases with septic shock were randomly
divided into two groups. Patients in both two groups revived after taking
effective liquid. Then dopamine was pumped into central veins of patients in the
research group (group DA) in 2 MU/(kg*min) upon the conventional treatment, while
nor epinephrine was pumped into patients in the control group (group NE) in 0.1
MU/(kg*min), besides conventional treatment. The improvement of haemodynamics and
microcirculation perfusion indexes were compared between two groups before and
after treatment, as well as the improvement of tissue oxygen metabolism. The
results demonstrated that, central venous pressure (CVP), mean arterial pressure
(MAP), urine volume and central venous oxygen saturation (Scv O2) in both groups
before treatment was not statistically significant (P>0.05); 6 h after treatment,
CVP, MAP, urine volume and Scv O2 of group NE were higher than group DA; 12h and
24h after treatment, blood lactic acid clearance of group NE was superior than
group DA (P<0.05). All the above findings suggested that, both dopamine and nor
epinephrine are beneficial to improve microcirculation and tissue oxygen
metabolism in the treatment of septic shock, and the clinical effect of nor
epinephrine was distinctly better than dopamine.
PMID- 26431659
TI - Hemorheological study and treatment with enema retention of Li Chong Tang
combined with moxibustion in women suffering from chronic pelvic inflammatory
diseases.
AB - The study was undertaken to investigate the blood stasis of chronic pelvic
inflammatory disease (PID) with scientific method, hemorheology. The whole blood
viscosities of chronic PID increased significantly compared with normal level,
which was consistent with the blood stasis of Traditional Chinese Medicine (TCM)
theory. Moreover, sixty women suffering from chronic PID were treated with Enema
Retention of Li Chong Tang Combined with Moxibustion (ERM) for 6 weeks. The
chronic PID score and the whole blood viscosity were evaluated before and after
the ERM. The parameters of whole blood viscosities at low, median and high shear
rate of chronic PID group decreased from 12.32+/-0.31, 6.66+/-0.13 and 5.15+/
0.52, to the normal levels, 9.19+/-0.13, 5.42+/-0.56 and 4.34+/-0.43 (p<0.05)
after therapy of ERM and the symptoms score decreased from 13.73+/-3.7 to 3.8+/
1.4 (p<0.05), which shows that the ERM is an effective therapy method to treat
chronic PID.
PMID- 26431660
TI - Clinical research on intravitreal injection of bevacizumab in the treatment of
macula lutea and retinal edema of ocular fundus disease.
AB - This paper aimed to explore clinically curative effect of intravitreal injection
of bevacizumab in the treatment of macula lutea and retinal edema of ocular
fundus disease. The number of 300 patients (390 eyes) with ocular fundus diseases
including retinal vein occlusion (RVO), diabetic retinopathy (DR), age-related
macular degeneration (ARMD), central serous chorioretinopathy (CSC), choridal new
vessel (CNV) received and cured in the hospital from February 2010 to February
2014 were given intravitreal injection of bevacizumab (1.5mg) with once per month
and a total of 2-3 times. Results of patients' vision and fluorescence fundus
angiography (FFA), optical coherence tomography (OCT) before and after treatment
were compared and curative effects were evaluated. Vision of 349 eyes (89.49%)
improved obviously with the average of more than 2 lines, patient's intraocular
pressure (IOP) was normal and all indexes were clearly better; vision of 26 eyes
(6.67%) was stable before the treatment and without any changes after the
treatment, the situation of fundus got better without increased IOP; vision of 15
eyes (3.85%) decreased to some extent, and the symptoms eased slightly after
symptomatic treatment. In the 1st day after intravitreal injection, best
corrected visual acuity increased to 0.239+/-0.175, best-corrected visual acuity
in 1 m was 0.315+/-0.182, in 3m continuously climbed to 0.350+/-0.270, and in 6 m
was 0.362+/-0.282. Compared with vision before injection, t value was t=3.184,
t=7.213, t=9.274 and t=9.970 (P=0.002, P=0.000, P=0.000 and P=0.000)
respectively, and all P were less than 0.01. Furthermore, the difference was
significant if a=0.01, which could confirm that 1m best corrected visual acuity
of patients after intravitreal injection improved clearly in combination with
before injection and 3m and 6 m visions enhanced constantly after injection. To
sum up, intravitreal injection of bevacizumab in treating ocular fundus disease
improves patient's vision effectively, also relieves macula lutea, retinal edema
and other symptoms obviously, and promotes the hemorrhage absorption of vitreous
body and retina.
PMID- 26431661
TI - Densitometric validation and analysis of biomarker beta-amyrin in different
Acacia species (leaves) grown in Kingdom of Saudi Arabia by high performance thin
layer chromatography.
AB - Biomarker beta-amyrin was analyzed in the leaves of four different Acacia species
(A. salicina, A. loreta, A. hamulosa and A. tortilis) grown in Kingdom of Saudi
Arabia by a validated HPTLC method. The chromatography was performed on glass
backed silica gel 60 F254 HPTLC plates using solvents toluene: methanol (9:1,
v/v) as mobile phase. The developed TLC plate was derivatized with anisaldehyde
and scanned at 520 nm. A sharp peak of beta-amyrin was found at Rf=0.58+/-0.01.
The r2 and the linear regression equation for beta-amyrin was found to be 0.991
and 19.913X+107.803, respectively in the concentration range of 100-800 ng. The
percentage of beta-amyrin was found to be maximum 2.70% w/w in A. tortilis, 1.85%
w/w in A. loreta and 1.80% w/w in A. hamulosa while it was totally absent in A.
salicina. This study conceives maiden reporting of quantification of beta-amyrin
in four different species of Acacia by validated HPTLC method. The developed
method for the analysis of beta-amyrin was proved to be reproducible by
statistical analysis hence it can be employed for further analysis of beta-amyrin
in plasma, other biological fluids and in finished products available in the
market.
PMID- 26431662
TI - The curative effect of adefovir dipivoxil treating HBeAg negative chronic
hepatitis B and treating HBeAg positive chronic hepatitis B combining interferon
alpha-2b.
AB - This study aimed to research the efficiency of adefovir dipivoxil in hepatitis B
e antigen (HBeAg)-negative chronic hepatitis B treatment and in combination with
alpha-2b interferon in the treatment of HBeAg-positive chronic hepatitis B. A
total of 102 cases of adult patients with HBeAg chronic hepatitis B were selected
for testing. HBeAg negative chronic hepatitis B patients took 10mg adefovir
dipivoxil capsules once daily, while positive chronic hepatitis B patients were
randomly divided into either a treatment group or a control group. The treatment
group was administrated with 10mg adefovir dipivoxil capsules, 1 time daily, and
injected with 5 million U Recombinant Human Interferon alpha-2b through muscle
every other day. The control group was treated with 10mg adefovir dipivoxil
capsules, 1 time per day. We examined alanine aminotransferase (ALT)
normalization and the Hepatitis B Virus (HBV)-DNA negative rate (undetectable
rate), as well as, HBeAg / hepatitis B e antibody (HBeAb) sero-conversion rate to
detect treatment effects. The results proved that after 6 months of medication
therapy, the ALT normalization rate was 49.9% and the HBV-DNA negative conversion
rate was 54.3%. 18 months into the treatment, showed an ALT normalization rate of
73.2%, while the HBV-DNA negative conversion rate grew to 76.8%. The use of
adefovir dipivoxil treatment of the negative chronic HBV has a certain extent
combined with alpha-2b Interferon therapy in treatment of HbeAg positive chronic
hepatitis B. After a 48-week observation period, ALT normalization and HBV-DNA
rate could not be measured, HBeAg/HBeAb sero-conversion rose higher, indicating
that the treatment of the combined drugs is more efficient than taking adefovir
dipivoxil by itself, and the data were comparable with the control group
(P<0.05). Thus adefovir dipivoxil can greatly improve the restrain function to
HBV-DNA and improve the immunity and control ability of the body, with obvious
short-term effects, in combination with Interferon.
PMID- 26431663
TI - In vivo anti-inflammatory, analgesic and antipyretic activities of a medicinal
plant, Caesalpinia bonducella F.
AB - This research examined antipyretic, anti-inflammatory, and analgesic activities
of ethanolic extract of C. bonducella whole seeds in experimental albino rats.
Three doses, 100, 200 and 400 mg/kg of the whole seed ethanolic extract prepared
as a suspension in 2 ml of 2% gum acacia were used. Acute inflammatory and
antipyretic activities were evaluated in experimental animals by carrageenan
induced paw edema and brewer's yeast-induced pyrexia models, respectively. A
significant (p<0.05) reduction in paw volumes, and pyrexia was noted in
experimental animals when compared with control animals. The ethanol see extract
(400 mg/kg) displayed in vivo anti-inflammatory, antipyretic and analgesic in
terms of reduction in paw edema, % writhes inhibition and rectal temperature by
(0.24+/-0.03), (31.38%) and (36.2+/-0.1), respectively. Overall the whole
ethanolic seed extract at all tested concentrations produced significant (p<0.05)
anti-inflammatory, antipyretic and analgesic activities. The results obtained in
this study clearly indicated the ethno-medicinal potential of C. bonducella in
curing pain and inflammation related disorders, supporting its efficacy as a
natural analgesic, antipyretic and anti-inflammatory agent.
PMID- 26431664
TI - Identification of essential regulatory elements responsible for the explicit
expression of IL-28Ralpha and their effect on critical SNPs using in-Silico
methods.
AB - IL-28Ralpha and IL10Rbeta collectively construct a fully functional hetero
dimeric receptor for type III interferons (IFNs). IL-28Ralpha is the private
chain for type III IFNs since their involvement in any other pathway has not been
reported yet and they are highly expressed in response to certain viral attack or
cancers. IL-28Ralpha is specific in their expression pattern and it expresses
within few cell types only. The regulatory mechanisms governing the expression of
IL-28Ralpha at the molecular level are not completely known yet and need to be
scrutinized at primary levels. In the present study, various in-silico techniques
were applied and it was observed that AP1-2, STAT 1-6, P-53, LyF-1 (lymphoid
transcription factor), c-Jun, PU.1, CREB (cAMP response element-binding), PLAG
(pleotropic adenoma gene), MYOD (myoblast determination protein 1), NOFL and KLFS
as transcription factors that are selected with preference. Interestingly AP-2, c
Jun, LyF-1, STAT, NF-Y and P53 have also been reported in literature recently as
some of the key regulatory elements as well. Based on the fact that interlinking
between different interferon stimulation genes (ISGs) is also not very clear and
induction of one type of interferon can affect the efficacy of the other, we
found that IFN-lambda4 induction can increase the expression of IL-28Ralpha,
similar to IFN-lambda3 but contrary to type I IFNs, which has either no effect on
the expression of IL-28Ralpha or can down regulate its expression at higher
concentrations (data not published).
PMID- 26431665
TI - The expression and significance of XIAP and C-jun on Condyloma acuminatum.
AB - Objective of the study was to investigate the expression and significance of XIAP
and c-jun in Condyloma acuminatum. The immunohistochemistry SABC method was
adopted to detect the expression of XIAP and c-jun in Condyloma acuminatum. The
positive expression rate of XIAP and c-jun in Condyloma acuminatum was 80%
(32/40) and 90% (36/40) separately and the intensity of expression was usually ++
~ +++. While in control group, the positive expression rate of XIAP and c-jun was
27.8% (5/18) and 16.7 % (3/18) separately, and the intensity of expression was -
~ ++. There was statistical significance of the positive expression rate and the
expression intensity of XIAP and c-jun between the two groups (P<0.05). Besides,
the positive correlation existed between expression of XIAP and c-jun (r=0.306
P<0.01). The over-expression of XIAP and c-jun in Condyloma acuminatum may be
associated with the growth of Condyloma acuminatum.
PMID- 26431666
TI - Report: Clinical curative effect of traditional Chinese medicine combined with
doxycycline in the treatment of genital Chlamydia trachomatis and Urea plasma
urealyticum infections.
AB - This paper aims to study clinical curative effect of traditional Chinese medicine
combined with doxycycline in treating genital Chlamydia trachomatis (Ct) and Urea
plasma urealyticum (Uu) infections. The observed subjects in this paper were 60
patients who had been randomly divided into two groups, among which the control
group was treated with doxycycline and the treatment group with Chinese medicine
combined with doxycycline. Results showed that the curative effect of the
treatment group was much better than that of the control. So it is proved that
Chinese medicine combined with doxycycline is worth promoting because it is a
convenient and safe way, which does not easily produce drug-resistant strain.
PMID- 26431667
TI - Review: Effect study of sex hormone in the multiple sclerosis of common
neurological disorders.
AB - Multiple sclerosis (MS) is one of most common neurological disorders, mainly
affecting women. The central nervous system (CNS) of this autoimmune disease is
characterized by intermittent or chronic damage to the myelin sheaths
(demyelination), local inflammation and axonal degeneration. During the early
relapsing/remitting stages of MS, myelin can regenerate. However, as the disease
progresses, both amount and activity of regenerated axons becomes insufficient,
leading to impaired axon conduction, neurodegeneration and the worsening
symptoms. Epidemiological study found that distinct symptom alleviation of
diseases at a certain periods would be shown in women during pregnancy. The
following basic researches indicated that sex hormones especially progesterone
can significantly reduce the disease severity, moreover, the protective effect of
sex hormone on the nervous system has become the research focus.
PMID- 26431668
TI - Treatment as usual and routine care in research and clinical practice.
AB - Treatment as usual (TAU) or routine care in the context of psychotherapy has been
used both as a control condition in clinical trials of evidence-based
psychotherapy (EBP) and as a primary therapeutic intervention. This article
considers TAU from both perspectives in which it is used and evaluated. First,
the strengths, limitations, and sources of ambiguity of using TAUs as control
conditions are discussed. Second, the evidence in behalf of TAUs is evaluated.
Reviews of the effectiveness of TAUs when contrasted with EBPs and when evaluated
in clinical applications and benchmarked against EBPs from clinical trials
suggest that both broad classes of treatments are effective and often equally
effective. The effectiveness of TAUs and the often similar outcomes evident in
comparison to EBPs raise research as well as clinical issues. The article
discusses research priorities for the evaluation of TAUs and clinical practices
that can improve both EBPs and TAUs in patient care.
PMID- 26431670
TI - The synthesis of recombinant membrane proteins in yeast for structural studies.
AB - Historically, recombinant membrane protein production has been a major challenge
meaning that many fewer membrane protein structures have been published than
those of soluble proteins. However, there has been a recent, almost exponential
increase in the number of membrane protein structures being deposited in the
Protein Data Bank. This suggests that empirical methods are now available that
can ensure the required protein supply for these difficult targets. This review
focuses on methods that are available for protein production in yeast, which is
an important source of recombinant eukaryotic membrane proteins. We provide an
overview of approaches to optimize the expression plasmid, host cell and culture
conditions, as well as the extraction and purification of functional protein for
crystallization trials in preparation for structural studies.
PMID- 26431669
TI - Live imaging of muscles in Drosophila metamorphosis: Towards high-throughput gene
identification and function analysis.
AB - Time-lapse microscopy in developmental biology is an emerging tool for functional
genomics. Phenotypic effects of gene perturbations can be studied non-invasively
at multiple time points in chronological order. During metamorphosis of
Drosophila melanogaster, time-lapse microscopy using fluorescent reporters allows
visualization of alternative fates of larval muscles, which are a model for the
study of genes related to muscle wasting. While doomed muscles enter hormone
induced programmed cell death, a smaller population of persistent muscles
survives to adulthood and undergoes morphological remodeling that involves
atrophy in early, and hypertrophy in late pupation. We developed a method that
combines in vivo imaging, targeted gene perturbation and image analysis to
identify and characterize genes involved in muscle development. Macrozoom
microscopy helps to screen for interesting muscle phenotypes, while confocal
microscopy in multiple locations over 4-5 days produces time-lapse images that
are used to quantify changes in cell morphology. Performing a similar
investigation using fixed pupal tissues would be too time-consuming and therefore
impractical. We describe three applications of our pipeline. First, we show how
quantitative microscopy can track and measure morphological changes of muscle
throughout metamorphosis and analyze genes involved in atrophy. Second, our assay
can help to identify genes that either promote or prevent histolysis of abdominal
muscles. Third, we apply our approach to test new fluorescent proteins as live
markers for muscle development. We describe mKO2 tagged Cysteine proteinase 1
(Cp1) and Troponin-I (TnI) as examples of proteins showing developmental changes
in subcellular localization. Finally, we discuss strategies to improve throughput
of our pipeline to permit genome-wide screens in the future.
PMID- 26431671
TI - Characterizing Energy Expenditure During Sedentary Behavior After Stroke.
AB - OBJECTIVES: To measure and calculate the energy expended by people with stroke
during near sedentary behaviors (lying, supported and unsupported sitting,
standing, wheelchair propulsion, walking), under controlled laboratory
conditions, and to compare these values with the energy expenditure of 1.5
metabolic equivalent task (MET) within the definition of sedentary behavior.
DESIGN: Cross-sectional cohort study. SETTING: Rehabilitation institutions.
PARTICIPANTS: People with stroke (N=27; mean age, 61.0+/-11.7y), categorized at
Functional Ambulation Categories (FAC) 0 to 5. INTERVENTIONS: Not applicable.
MAIN OUTCOME MEASURES: Energy expenditure (measured using indirect calorimetry)
expressed in METs. The recorded values were calculated for every participant and
averaged for each activity: lying, supported and unsupported sitting, standing,
wheelchair propulsion, and walking. Calculations were done for the total group
and categorized by the FAC. RESULTS: For the total group the mean METs +/- SDs
were 1.04+/-.11 for sitting supported, 1.09+/-.15 for sitting unsupported, 1.31+/
.25 for standing, 1.91+/-.42 for wheelchair propulsion, and 2.52+/-.55 for
walking. People with stroke in all FAC had METs values >1.5 when propelling a
wheelchair or walking. CONCLUSIONS: Energy expenditure during typical sedentary
behaviors (ie, sitting) is narrowly bounded at approximately 1.0 MET. Energy
expenditure during sitting and standing was <=1.5 MET for all FAC, with the
exception of FAC 0 (1.6 MET during standing). Independent wheelchair propulsion
and walking can be categorized as light activities (>=1.5 MET).
PMID- 26431672
TI - Bone metabolism induced by denture insertion in positron emission tomography.
AB - 18F-fluoride positron emission tomography (PET) can identify subtle functional
variation prior to the major structural change detectable by X-ray. This study
aims to investigate the mechanobiological bone reaction around the abutment tooth
and in the residual ridge, induced by insertion of removable partial denture
(RPD) within two different groups of patients: patients without denture
experience (Group 1) and patients with denture experience before (Group 2), using
18F-fluoride PET imaging technique. 18F-fluoride PET/computerised tomography (CT)
scan was performed to examine the bone metabolic change in mandible before and
after the RPD treatment. Region of interests (ROIs) were placed in alveolar bone
around abutment tooth and in residual bone beneath the RPD. Standardised uptake
value (SUV), reflecting the accumulation of 18F-fluoride, was measured for each
ROI. In all subjects of Group 1, SUVs after insertion were higher than before in
both alveolar bone and residual bone, while there was less significant change in
SUV in subjects of Group 2. This study demonstrated using longitudinal 18F
fluoride PET scans to effectively examine the bone metabolic change in mandible
induced by occlusal loading after RPD insertion. Using this technique, within the
six subjects in this study, it was shown that bone metabolism around abutment
tooth and residual ridge increased after RPD insertion in case of first-time
denture user, while there was no big change in the patient with experience of
denture before. This study revealed the effectiveness of applying PET to evaluate
bone metabolic activity as mechanobiological reaction.
PMID- 26431673
TI - Chemically induced dimerization: reversible and spatiotemporal control of protein
function in cells.
AB - Small-molecule perturbation of biological systems is able to tackle biological
problems that are not accessible by classical genetic interference methods.
Chemically induced dimerization (CID) has been used as a valuable tool to study
various biological processes. Recent years have seen tremendous progress in the
development of orthogonal and reversible CID systems. These new systems allow
control over protein function with unprecedented precision and spatiotemporal
resolution. While the primary application of CID has been on dissecting signal
transductions, new emerging approaches have extended the scope of this technique
to elucidating membrane and protein trafficking.
PMID- 26431674
TI - Bioinformatics Prediction and In Vitro Analysis Revealed That miR-17 Targets
Cyclin D1 mRNA in Triple Negative Breast Cancer Cells.
AB - Breast cancer is one of the most prevalent malignancies among women worldwide.
Triple negative breast cancer (TNBC) is a type of breast cancer in which estrogen
receptor, progesterone receptor, and human epidermal growth factor receptor 2
(HER-2) are not expressed. There is no targeted therapy for this type of cancer,
and available therapies have poor therapeutic effects. Performing a preliminary
research, we selected cyclin D1 (CCND1) gene of Wnt signaling pathway which is a
target of miRNAs, a promising set of biomolecules in diagnosis and treatment of
breast cancer. In this study using bioinformatic analyses, miR-17 was selected as
it targets the 3'UTR of CCND1 gene with the highest score. Luciferase assay
results also confirmed the bioinformatic prediction. Decreased expression of miR
17 in MDA-MB-231 cell line was observed using qRT-PCR method. After lentiviral
transduction of miR-17 to the target cells, gene expression analysis showed
decreased expression of CCND1 gene. We found miR-17 as an attractive molecule
that after intensive research can probably be used as a biomarker in TNBC.
PMID- 26431676
TI - Switching between Epigenetic States at Pericentromeric Heterochromatin.
AB - Pericentromeric DNA represents a large fraction of the mammalian genome that is
usually assembled into heterochromatin. Recent advances have revealed that the
composition of pericentromeric heterochromatin is surprisingly dynamic. Indeed,
high levels of histone H3 trimethylation on lysine 9 (H3K9me3) and DNA
methylation normally characterize the repressive environment of this region.
However, in specific tissues and in cancer cells, Polycomb proteins can occupy
pericentromeric heterochromatin and act as a molecular sink for transcriptional
regulators. Restoring heterochromatin methylation marks could, thus, be an
important way to bring back normal gene expression programs in disease. Here, I
discuss the potential mechanisms by which Polycomb complexes are recruited to
pericentromeric DNA.
PMID- 26431677
TI - Forecasting waste compositions: A case study on plastic waste of electronic
display housings.
AB - Because of the rapid succession of technological developments, the architecture
and material composition of many products used in daily life have drastically
changed over the last decades. As a result, well-adjusted recycling technologies
need to be developed and installed to cope with these evolutions. This is
essential to guarantee continued access to materials and to reduce the ecological
impact of our material consumption. However, limited information is currently
available on the material composition of arising waste streams and even less on
how these waste streams will evolve. Therefore, this paper presents a methodology
to forecast trends in the material composition of waste streams. To demonstrate
the applicability and value of the proposed methodology, it is applied to
forecast the evolution of plastic housing waste from flat panel display (FPD)
TVs, FPD monitors, cathode ray tube (CRT) TVs and CRT monitors. The results of
the presented forecasts indicate that a wide variety of plastic types and
additives, such as flame retardants, are found in housings of similar products.
The presented case study demonstrates that the proposed methodology allows the
identification of trends in the evolution of the material composition of waste
streams. In addition, it is demonstrated that the recycling sector will need to
adapt its processes to deal with the increasing complexity of plastics of end-of
life electronic displays while respecting relevant directives.
PMID- 26431675
TI - Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy.
AB - Host-pathogen interactions provide valuable systems for the study of evolutionary
genetics and natural selection. The sequestration of essential iron has emerged
as a crucial innate defense system termed nutritional immunity, leading pathogens
to evolve mechanisms of 'iron piracy' to scavenge this metal from host proteins.
This battle for iron carries numerous consequences not only for host-pathogen
evolution but also microbial community interactions. Here we highlight recent and
potential future areas of investigation on the evolutionary implications of
microbial iron piracy in relation to molecular arms races, host range,
competition, and virulence. Applying evolutionary genetic approaches to the study
of microbial iron acquisition could also provide new inroads for understanding
and combating infectious disease.
PMID- 26431678
TI - The use of organic wastes at different degrees of maturity as carbon sources for
denitrification of landfill leachate.
AB - In this study different garden refuses were investigated to ascertain their
efficiency to act as carbon sources in a denitrification system. Six different
garden refuse materials were studied: commercial and domestic garden refuse raw
(CGR RAW, DGR RAW), immaturely composted domestic and commercial garden refuse
(DGR 10 and CGR 10 respectively), commercial garden refuse composted by Dome
Aeration Technology and by "turned windrow" technology (DAT and TW). Different
concentrations of synthetic nitrate solution were used to assess the efficiency
of each substrate. The results demonstrate that all substrates were able to
sustain the denitrification process. However, due to its higher C/N ratio the CGR
RAW was the better performing of the materials, reaching 100% removal after 8 and
12h for the 100 and 500 mg L(-1) respectively and after 11 days for 2000 mg L(
1). Kinetic studies revealed that the zero-order reaction better describes the
process indicating a denitrification rate independent from the nitrate
concentrations investigated when 100 and 500 mg L(-1) of nitrate were used. The
study demonstrated the suitability of organic municipal solid wastes to sustain
denitrification, opening a new scenario towards a low cost and in situ solution
for treatment of landfill leachate by using wastes, otherwise disposed of in
landfill.
PMID- 26431679
TI - Cooking and disgust sensitivity influence preference for attending insect-based
food events.
AB - Insects are energy-efficient and sustainable sources of animal protein in a world
with insufficient food resources to feed an ever-increasing population. However,
much of the western world refuses to eat insects because they perceive them as
disgusting. This research finds that both animal reminder disgust and core
disgust reduced people's willingness to attend a program called "Bug Appetit" in
which insects were served as food. Additionally, people who were low in
sensitivity to animal reminder disgust were more willing to attend this program
after having been primed to think about cooking. Cooking is a process by which
raw ingredients are transformed into finished products, reducing the "animalness"
of meat products that renders them disgusting. Sensitivity to core disgust did
not interact with cooking to influence willingness to attend the program. While
prior research has emphasized that direct education campaigns about the benefits
of entomophagy (the consumption of insects) can increase willingness to attend
events at which insect-based food is served, this is the first demonstration that
indirect priming can have a similar effect among a subset of the population.
PMID- 26431680
TI - Relationships between nutrition-related knowledge, self-efficacy, and behavior
for fifth grade students attending Title I and non-Title I schools.
AB - The Social Cognitive Theory (SCT) is a widely used theory for nutrition education
programming. Better understanding the relationships between knowledge, self
efficacy, and behavior among children of various income levels can help to form
and improve nutrition programs, particularly for socioeconomically disadvantaged
youth. The purpose of this study was to determine the relationships between
knowledge, self-efficacy, and behavior among fifth grade students attending Title
I (>=40% of students receiving free or reduced school meals) and non-Title I
schools (<40% of students receiving free or reduced school meals). A validated
survey was completed by 55 fifth grade students from Title I and 122 from non
Title I schools. Differences in knowledge, self-efficacy, and behavior scores
between groups were assessed using t test and adjusted for variations between
participating schools. Regression analysis was used to determine the
relationships between knowledge, self-efficacy, and behavior. In adjusted models,
the Title I group had significantly lower scores on several knowledge items and
summary knowledge (P = 0.04). The Title I group had significantly lower scores on
several behavior variables including intakes of fruits (P = 0.02), vegetables (P
= 0.0005), whole grains (P = 0.0003), and lean protein (P = 0.047), physical
activity (P = 0.002) and summary behavior (P = 0.001). However the Title I group
scored higher on self-efficacy for meal planning (P = 0.04) and choosing healthy
snacks (P = 0.036). Both self-efficacy (beta = 0.70, P < 0.0001) and knowledge
(beta = 0.35, P = 0.002) strongly predicted behavior; however, only self-efficacy
remained significant in the Title I group (self-efficacy, beta = 0.82, P =
0.0003; knowledge, beta = 0.11, P = 0.59). Results demonstrate disparities in
nutrition knowledge and behavior outcomes between students surveyed from Title I
and non-Title I schools, suggesting more resources may be necessary for lower
income populations. Findings suggest that future nutrition interventions should
focus on facilitating the improvement of children's self-efficacy.
PMID- 26431683
TI - Individual differences in bitter taste preferences are associated with antisocial
personality traits.
AB - In two studies, we investigated how bitter taste preferences might be associated
with antisocial personality traits. Two US American community samples (total N =
953; mean age = 35.65 years; 48% females) self-reported their taste preferences
using two complementary preference measures and answered a number of personality
questionnaires assessing Machiavellianism, psychopathy, narcissism, everyday
sadism, trait aggression, and the Big Five factors of personality. The results of
both studies confirmed the hypothesis that bitter taste preferences are
positively associated with malevolent personality traits, with the most robust
relation to everyday sadism and psychopathy. Regression analyses confirmed that
this association holds when controlling for sweet, sour, and salty taste
preferences and that bitter taste preferences are the overall strongest predictor
compared to the other taste preferences. The data thereby provide novel insights
into the relationship between personality and the ubiquitous behaviors of eating
and drinking by consistently demonstrating a robust relation between increased
enjoyment of bitter foods and heightened sadistic proclivities.
PMID- 26431682
TI - Exogenous glucagon-like peptide-1 acts in sites supplied by the cranial
mesenteric artery to reduce meal size and prolong the intermeal interval in rats.
AB - Three experiments were done to better assess the gastrointestinal (GI) site(s) of
action of GLP-1 on food intake in rats. First, near-spontaneous nocturnal chow
meal size (MS), intermeal intervals (IMI) length and satiety ratios (SR = MS/IMI)
were measured after infusion of saline, 0.025 or 0.5 nmol/kg GLP-1 into the
celiac artery (CA, supplying the stomach and upper duodenum), cranial mesenteric
artery (CMA, supplying small and all of the large intestine except the rectum),
femoral artery (FA, control) or portal vein (PV, control). Second, infusion of
0.5 nmol/kg GLP-1 was tested after pretreatment with the GLP-1 receptor (GLP-1R)
antagonist exendin-4(3-39) via the same routes. Third, the regional distribution
of GLP-1R in the rat GI tract was determined using rtPCR. CA, CMA and FA GLP-1
reduced first MS relative to saline, with the CMA route more effective than the
others. Only CMA GLP-1 prolonged the IMI. None of the infusions affected second
MS or later eating. CA and CMA GLP-1 increased the SR, with the CMA route more
effective than the CA route. CMA exendin-4 (3-39) infusion reduced the effect of
CMA GLP-1. Finally GLP-1R expression was found throughout the GI tract. The
results suggest that exogenous GLP-1 acts in multiple GI sites to reduce feeding
under our conditions and that GLP-1R in the area supplied by the CMA, i.e., the
small and part of the large intestine, plays the leading role.
PMID- 26431684
TI - Focus on the future: Episodic future thinking reduces discount rate and snacking.
AB - Obesity seems related to a preference for immediate gratification. By changing
this focus on short term benefits to a more future-oriented outlook, delay
discounting (impulsive decision making) can be changed by a manipulation of
episodic future thinking (EFT). EFT comprises a vivid mental simulation of
general future experiences. EFT may also affect consumption of unhealthy foods,
which can be seen as a choice for immediate gratification. Recent research shows
that future orientation should be tailored to the behavior at outcome. We
therefore hypothesize that the effectiveness of EFT on food intake could be
enhanced by making the content food-related. We conducted a 2 (future vs past
thinking) by 2 (food vs non-food related thoughts) between-subject design
experiment in female undergraduates (N = 94), to compare the efficacy of EFT
versus the recalling of episodic past events in reducing discount rate and
caloric intake. Content of imagery was either unrestricted or food-related.
Participants engaged in EFT or control episodic imagery while snacks were offered
to freely consume, and next the Monetary Choice Questionnaire was completed as a
measure of delay discounting, while again being engaged in EFT or control
imagery. Both types of EFT reduced delay discounting, however, only food-related
EFT lead to more restricted caloric consumption. Thus, we found evidence that EFT
reduced discount rate during decision making. However, in order to restrict
caloric intake, EFT should entail food-related imagery. As discount rate and
caloric intake were not related in the current sample, the underlying mechanism
remains to be discovered. Results however suggest that EFT is a promising
technique to resist immediate gratification.
PMID- 26431685
TI - An (un)healthy poster: When environmental cues affect consumers' food choices at
vending machines.
AB - Environmental cues can affect food decisions. There is growing evidence that
environmental cues influence how much one consumes. This article demonstrates
that environmental cues can similarly impact the healthiness of consumers' food
choices. Two field studies examined this effect with consumers of vending machine
foods who were exposed to different posters. In field study 1, consumers with a
health-evoking nature poster compared to a pleasure-evoking fun fair poster or no
poster in their visual sight were more likely to opt for healthy snacks.
Consumers were also more likely to buy healthy snacks when primed by an activity
poster than when exposed to the fun fair poster. In field study 2, this consumer
pattern recurred with a poster of skinny Giacometti sculptures. Overall, the
results extend the mainly laboratory-based evidence by demonstrating the health
relevant impact of environmental cues on food decisions in the field. Results are
discussed in light of priming literature emphasizing the relevance of preexisting
associations, mental concepts and goals.
PMID- 26431686
TI - Meeting report: 28th International Conference on Antiviral Research in Rome,
Italy.
AB - The 28th International Conference on Antiviral Research (ICAR) was held in Rome,
Italy from May 11 to 15, 2015. This article summarizes the principal invited
lectures. Phillip Furman, the Elion award recipient, described the research
leading to sofosbuvir. Dennis Liotta, who received the Holy award, described how
an investigation into HIV entry inhibitors led to a new therapy for cancer
patients. Erica Ollmann Saphire, winner of the Prusoff Young Investigator award,
explored the world of viral proteins and how they remodel to perform different
essential roles in viral replication. The keynote addresses, by Raffaele De
Francesco and Michael Manns, reported on the remarkable progress made in the
therapy of chronic HCV infections. A third keynote address, by Armand Sprecher,
related the difficulties and successes of Medicins Sans Frontieres in West Africa
ravaged by the Ebola outbreak. There were three mini-symposia on RNA Viruses,
Antiviral Chemistry and Emerging Viruses. There was a good collection of talks on
RNA viruses (norovirus, rabies, dengue, HEV, HCV, and RSV). A highlight of the
chemistry was the preparation of prodrugs for nucleotide triphosphates as this
opens a door to new options. The third mini-symposium emphasized how research
work in the antiviral area is continuing to expand and needs to do so with a
sense of urgency. Although this meeting report covers only a few of the
presentations, it aims to illustrate the great diversity of topics discussed at
ICAR, bringing together knowledge and expertise from the whole spectrum of
antiviral research.
PMID- 26431681
TI - Managing temptation in obesity treatment: A neurobehavioral model of intervention
strategies.
AB - Weight loss outcomes in lifestyle interventions for obesity are primarily a
function of sustained adherence to a reduced-energy diet, and most lapses in diet
adherence are precipitated by temptation from palatable food. The high
nonresponse and relapse rates of lifestyle interventions suggest that current
temptation management approaches may be insufficient for most participants. In
this conceptual review, we discuss three neurobehavioral processes (attentional
bias, temporal discounting, and the cold-hot empathy gap) that emerge during
temptation and contribute to lapses in diet adherence. Characterizing the
neurobehavioral profile of temptation highlights an important distinction between
temptation resistance strategies aimed at overcoming temptation while it is
experienced, and temptation prevention strategies that seek to avoid or minimize
exposure to tempting stimuli. Many temptation resistance and temptation
prevention strategies heavily rely on executive functions mediated by prefrontal
systems that are prone to disruption by common occurrences such as stress,
insufficient sleep, and even exposure to tempting stimuli. In contrast,
commitment strategies are a set of devices that enable individuals to manage
temptation by constraining their future choices, without placing heavy demands on
executive functions. These concepts are synthesized in a conceptual model that
categorizes temptation management approaches based on their intended effects on
reward processing and degree of reliance on executive functions. We conclude by
discussing the implications of our model for strengthening temptation management
approaches in future lifestyle interventions, tailoring these approaches based on
key individual difference variables, and suggesting high-priority topics for
future research.
PMID- 26431687
TI - Immediate loading of two freestanding implants placed by computer-guided flapless
surgery supporting a mandibular overdenture with magnetic attachments.
AB - PURPOSE: The present article describes a novel clinical procedure for mandibular
overdentures supported by two freestanding implants loaded immediately after
placement via computer-guided flapless surgery. METHODS: A conventional acrylic
complete denture was fabricated, and CT scans obtained using the denture as a
radiographic guide. Preoperative computer-assisted planning was performed using
commercially available software, permitting simulation of implant placement at
optimal positions. Using simulation data, a surgical guide was manufactured and
used during surgery. The surgical guide was placed and local anesthesia injected
for drilling of anchor pins to stabilize the surgical guide. The drilling
protocol for each osteotomy site achieved an insertion torque greater than 35
Ncm. Immediately after implant placement, a keeper of the magnetic attachment was
connected to each implant, and the magnetic assembly incorporated into the
denture. The mucosal surface of the denture around the magnet was relieved to
avoid excessive tissue pressure. The patients were instructed to wear the denture
in place continually for the following 7 days. After six months of healing and
follow-up, a final denture with a metal framework may be fabricated if necessary.
CONCLUSION: A novel treatment protocol for immediately loaded implant-supported
mandibular overdentures is described in detail. The protocol ensures secure
precise and safe implant placement, successful osseointegration, and immediate
improvement of oral health-related quality of life for patients with unstable
complete dentures.
PMID- 26431688
TI - Molecular characterization and specific detection of Anaplasma species (AP-sd) in
sika deer and its first detection in wild brown bears and rodents in Hokkaido,
Japan.
AB - A previously undescribed Anaplasma species (herein referred to as AP-sd) has been
detected in sika deer, cattle and ticks in Japan. Despite being highly similar to
some strains of A. phagocytophilum, AP-sd has never been detected in humans. Its
ambiguous epidemiology and the lack of tools for its specific detection make it
difficult to understand and interpret the prevalence of this Anaplasma species.
We developed a method for specific detection, and examined AP-sd prevalence in
Hokkaido wildlife. Our study included 250 sika deer (Cervus nippon yesoensis), 13
brown bears (Ursus arctos yesoensis) and 252 rodents including 138 (Apodemus
speciosus), 45 (Apodemus argenteus), 42 (Myodes rufocanus) and 27 (Myodes
rutilus) were collected from Hokkaido island, northern Japan, collected during
2010 to 2015. A 770 bp and 382 bp segment of the 16S rRNA and gltA genes,
respectively, were amplified by nested PCR. Results were confirmed by cloning and
sequencing of the positive PCR products. A reverse line blot hybridization (RLB)
based on the 16S rRNA gene was then developed for the specific detection of AP
sd. The prevalence of AP-sd by nested PCR in sika deer was 51% (128/250). We
detected this Anaplasma sp. for the first time in wild brown bears and rodents
with a prevalence of 15% (2/13) and 2.4% (6/252), respectively. The sequencing
results of the 16S rRNA and gltA gene amplicons were divergent from the selected
A. phagocytophilum sequences in GenBank. Using a newly designed AP-sd specific
probe for RLB has enabled us to specifically detect this Anaplasma species.
Besides sika deer and cattle, wild brown bears and rodents were identified as
potential reservoir hosts for AP-sd. This study provided a high throughput
molecular method that specifically detects AP-sd, and which can be used to
investigate its ecology and its potential as a threat to humans in Japan.
PMID- 26431689
TI - Diversity of VP7 genes of G1 rotaviruses isolated in Iran, 2009-2013.
AB - Genotype G1 of rotaviruses (RVs) is the most prevalent strain in human RV
infections around the world. The present study evaluated genetic variations in
the VP7 gene of RV G1 genotype isolates from Iran. Genetic and phylogenetic
analyses indicated that RV strains from Iran clustered with G1 lineages IA, IC,
and IIC, showing highest average of similarity versus reference sequences of the
G1 lineages I and II. This study highlights the genetic pattern of G1 RV on the
basis of distinct lineages and sublineages and indicates the importance of
continuous monitoring on genetic variation and evolution pattern of G1 RV strains
across the Iranian population for the final aim of RV vaccine introduction.
PMID- 26431690
TI - A deep phylogeny of viral and cellular right-hand polymerases.
AB - Right-hand polymerases are important players in genome replication and repair in
cellular organisms as well as in viruses. All right-hand polymerases are grouped
into seven related protein families: viral RNA-dependent RNA polymerases, reverse
transcriptases, single-subunit RNA polymerases, and DNA polymerase families A, B,
D, and Y. Although the evolutionary relationships of right-hand polymerases
within each family have been proposed, evolutionary relationships between
families remain elusive because their sequence similarity is too low to allow
classical phylogenetic analyses. The structure of viral RNA-dependent RNA
polymerases recently was shown to be useful in inferring their evolution. Here,
we address evolutionary relationships between right-hand polymerase families by
combining sequence and structure information. We used a set of 22 viral and
cellular polymerases representing all right-hand polymerase families with known
protein structure. In contrast to previous studies, which focused only on the
evolution of particular families, the current approach allowed us to present the
first robust phylogenetic analysis unifying evolution of all right-hand
polymerase families. All polymerase families branched into discrete lineages,
following a fairly robust adjacency pattern. Only single-subunit RNA polymerases
formed an inner group within DNA polymerase family A. RNA-dependent RNA
polymerases of RNA viruses and reverse transcriptases of retroviruses formed two
sister groups and were distinguishable from all other polymerases. DNA
polymerases of DNA bacteriophages did not form a monophyletic group and are
phylogenetically mixed with cellular DNA polymerase families A and B. Based on
the highest genetic variability and structural simplicity, we assume that RNA
dependent RNA polymerases are the most ancient group of right-hand polymerases,
in agreement with the RNA World hypothesis, because RNA-dependent RNA polymerases
are enzymes that could serve in replication of RNA genomes. Moreover, our results
show that protein structure can be used in phylogenetic analyses of distantly
related proteins that share only limited sequence similarity.
PMID- 26431691
TI - Demographic and developmental differences in the content and sequence of
adolescents' ideal romantic relationship behaviors.
AB - This study utilizes data from 18,392 respondents (aged 12-19) in Wave 1 of the
National Longitudinal Study of Adolescent to Adult Health (Add Health) to provide
a detailed descriptive analysis of U.S. adolescents' desired behaviors in their
ideal romantic relationships. Age, gender, and ethnic group differences in the
desire for--and preferred sequence of--a set of activities that could occur in a
hypothetical romantic relationship were explored within subsets of heterosexual
(n = 17,274) and sexual minority adolescents (n = 1118). Non-sexual behaviors
were more commonly desired compared to sexual behaviors. The typical desired
behavioral sequence was: holding hands, going out alone, telling others they were
a couple, kissing, saying "I love you," sexual touching, and finally having sex.
Overall, more similarities than differences emerged across groups, with some
notable differences in the percentages who desired sexual behaviors. Results
provide a nuanced picture of adolescent relationship scripts, with implications
for education and prevention.
PMID- 26431692
TI - Maternal separation activates microglial cells and induces an inflammatory
response in the hippocampus of male rat pups, independently of hypothalamic and
peripheral cytokine levels.
AB - Adult animals subjected to chronic stress show an inflammatory response in the
hippocampus which has been related to cognitive dysfunction and psychopathology.
However the immediate consequences of early life stress on hippocampal glial
cells have not been studied. Here we analyzed the effects of maternal separation
(MS) on astrocyte and microglial cell morphology in the hippocampal hilus,
compared the expression of cytokines in the hippocampus and hypothalamus, and the
peripheral response of cytokines, on postnatal day (PD) 15. Male rat pups of MS
(3h/day, PD1-PD14) and Control (CONT) pups showed similar microglial cell
densities in the hilus, but MS pups presented more activated microglia. MS
decreased astrocyte density and the number of processes in the hilus. Cytokine
mRNA expression (qPCR) was analyzed in MS and CONT groups, sacrificed (i) under
basal (B) conditions or (ii) after a single stress event (SS) at PN15. In
hippocampal extracts, MS increased IL-1beta mRNA, under B and SS conditions while
IL-6 and TNF-alpha did not change. In hypothalamic tissue, MS increased TNF-alpha
and IL-6 mRNA, but not IL-1b, after SS. Peripheral concentrations of IL-1beta
were decreased under B and SS conditions in MS; IL-6 concentration increased
after SS in MS pups, and TNF-alpha concentration was unchanged. In conclusion, MS
activates microglial cells and decreases astrocyte density in the hippocampus. A
differential cytokine expression is observed in the hippocampus and the
hypothalamus after MS, and after SS. Also, MS triggers an independent response of
peripheral cytokines. These specific responses together could contribute to
decrease hippocampal neurogenesis and alter the neuroendocrine axis.
PMID- 26431693
TI - It takes two to tango: Phagocyte and lymphocyte numbers in a small mammalian
hibernator.
AB - Immunity is energetically costly and competes for resources with other
physiological body functions, which may result in trade-offs that impair fitness
during demanding situations. Endocrine mediators, particularly stress hormones,
play a central role in these relationships and directly impact leukocyte
differentials. To determine the effects of external stressors, energetic
restraints and competing physiological functions on immune parameters and their
relevance for fitness, we investigated leukocyte profiles during the active
season of a small obligate hibernator, the edible dormouse (Glis glis), in five
different study sites in south-western Germany. The highly synchronized yearly
cycle of this species and the close adaptation of its life history to the
irregular abundance of food resources provide a natural experiment to elucidate
mechanisms underlying variations in fitness parameters. In contrast to previous
studies on hibernators, that showed an immediate recovery of all leukocyte
subtypes upon emergence, our study revealed that hibernation results in depleted
phagocyte (neutrophils and monocytes) stores that recovered only slowly. As the
phenomenon of low phagocyte counts was even more pronounced at the beginning of a
low food year and primarily immature neutrophils were present in the blood upon
emergence, preparatory mechanisms seem to determine the regeneration of
phagocytes before hibernation is terminated. Surprisingly, the recovery of
phagocytes thereafter took several weeks, presumably due to energetic
restrictions. This impaired first line of defense coincides with lowest survival
probabilities during the annual cycle of our study species. Reduced survival
could furthermore be linked to drastic increases in the P/L ratio
(phagocytes/lymphocytes), an indicator of physiological stress, during
reproduction. On the other hand, moderate augmentations in the P/L ratio occurred
during periods of low food availability and were associated with increased
survival, but reproductive failure. In this case, the stress response probably
represents an adaptive reaction that contributes to survival by activating energy
resources. In contrast to our expectation, we could not detect an amplification
of stress through high population densities. Summarized, results of our study
clearly reveal that the leukocyte picture of active edible dormice responds
sensitively to physiological conditions associated with hibernation, reproductive
activity and food availability and can be linked to fitness parameters such as
survival. Thus edible dormice represent an excellent model organism to
investigate regulatory mechanisms of the immune system under natural conditions.
PMID- 26431694
TI - Urological complications, vesicoureteral reflux, and long-term graft survival
rate after pediatric kidney transplantation.
AB - To describe a single-center experience with kidney transplantation and then study
some donor and recipient features that may impact on graft survival and
urological complication rates. We reviewed our database searching for pediatric
patients who underwent kidney transplantation from August 1985 through November
2012. Preoperative data and postoperative complications were recorded. Graft
survival rates were analyzed and compared based on the type of donor, donor's age
from deceased donors, and recipients' ESRD cause. Kaplan-Meier curves with log
rank and Wilcoxon tests were used to perform the comparisons. There were 305
pediatric kidney transplants. The mean recipient's age was 11.7 yr. The mean
follow-up was 11.0 yr. Arterial and venous thrombosis rates were 1.6% and 2.3%,
respectively, while urinary fistula and symptomatic vesicoureteral reflux were
diagnosed in 2.9% and 3.6% of cases, respectively. Deceased kidney
transplantation had a lower graft survival rate than living kidney
transplantation (log rank, p = 0.005). Donor's age (p = 0.420) and ESRD cause (p
= 0.679) were not significantly related to graft survival rate. In long-term
follow-up, type of donor, but not donor's age, impacts on graft survival rate.
ESRD cause has no impact on graft survival rate, showing that well-evaluated
recipients may have good outcomes.
PMID- 26431695
TI - Validation of the howRu and howRwe questionnaires at the individual patient
level.
AB - BACKGROUND: The howRu and howRwe are new short questionnaires which are meant to
measure health-related quality of life and patient experience. However,
validation at the individual patient level has not yet taken place. We aimed to
investigate the validity of both questionnaires at the individual patient level.
METHODS: In this prospective validation study, patients were asked to complete
both questionnaires and comment on their answers in a semi-structured in-depth
interview. Based on the transcribed interviews, a panel of 45 general
practitioners and 45 patients filled out the questionnaires as they thought the
patients had completed them. The questionnaires were considered valid instruments
when a reliable and acceptable level of agreement was reached between the
patient's score and the score of a review panel, defined as a concordance
correlation coefficient (CCC) of >=0.70. Bland-Altman plots were also made.
RESULTS: Ninety patients were included. The CCC of the howRu total score of the
review panel and patients was 0.80 (95 % CI 0.73 to 0.86). Bland-Altman plots
showed a mean difference of -0.96 and the limits of agreement ranged from -2.87
to 0.95. The CCC of the howRwe total score was 0.57 (95 % CI 0.42 to 0.69). The
mean difference on the Bland-Altman plots was -0.54 and the limits of agreement
ranged from -3.59 to 2.52. CONCLUSIONS: The howRu seems to be a valid
questionnaire for measuring health-related quality of life at the individual
patient level. We do not advice to use the tested version of the howRwe
questionnaire for assessing patient experience at the individual patient level.
TRIAL REGISTRATION: The study was registered at clinicaltrials.gov NCT01830803 .
Registration date: 5 April 2013.
PMID- 26431696
TI - Prevalence and characteristics of coronary artery anomalies in an adult
population undergoing multidetector-row computed tomography for the evaluation of
coronary artery disease.
AB - BACKGROUND: Congenital coronary anomalies are uncommon with an incidence ranging
from 0.17 % in autopsy cases to 1.2 % in angiographically evaluated cases. The
recent development of ECG-gated multi-detector row computed tomography (MDCT)
coronary angiography allows accurate and noninvasive depiction of coronary artery
anomalies. METHODS: This retrospective study included 2572 patients who underwent
coronary 64-slice MDCT coronary angiography from January 2008 to March 2012.
Coronary angiographic scans were obtained with injection of 80 ml nonionic
contrast medium. Retrospective gating technique was used to synchronize data
reconstruction with the ECG signal. Maximum intensity projection, multi-planar
reformatted, and volume rendering images were derived from axial scans. RESULTS:
Of the 2572 patients, sixty (2.33 %) were diagnosed with coronary artery
anomalies (CAAs), with a mean age of 53.6 +/- 11.8 years (range 29-80 years).
High take-off of the RCA was seen in 16 patients (0.62 %), of the left main
coronary artery (LMCA) in 2 patients (0.08 %) and both of them in 2 patients
(0.08 %). Separate origin of the left anterior descending artery (LAD) and left
circumflex artery (LCx) from left sinus of Valsalva (LSV) was found in 15
patients (an incidence of 0.58 %). In 9 patients (0.35 %) the right coronary
artery (RCA) arose from the opposite sinus of Valsalva with a separate ostium. In
6 patients (0.23 %) an abnormal origin of LCX from the right sinus of Valsalva
(RSV) was found with a further posterior course within the atrioventricular
groove. A single coronary artery was seen in 3 patients (0.12 %). It originated
from the right sinus of Valsalva in one patient and from LSV in two patients. In
two other patients (0.08 %) the left coronary trunk originated from the RSV with
separate ostium from the RCA. LCA originating from the pulmonary artery was found
in one patient (0.04 %). A coronary artery fistula, which is a termination
anomaly, was detected in 4 patients (0.15 %). DISCUSSION: Although these
anomalies, which are remarkably different from the normal structure, exist as
early as birth, they are incidentally encountered during selective angiography or
at autopsy. The incidence in reported angiographic series ranges from 0.6 % to
1.3 %. Variations in the frequency of primary congenital coronary anomalies may
possibly have a genetic background. The largest angiographic series of 126595
patients, by Yamanaka and Hobbs, reported a 1.3 % incidence of anomalous coronary
artery. CONCLUSION: The results of this study support the use MDCT coronary
angiography as a safe and effective noninvasive imaging modality for defining
CAAs in an appropriate clinical setting, providing detailed three-dimensional
anatomic information that may be difficult to obtain with invasive angiography.
PMID- 26431697
TI - Parental views of children's physical activity: a qualitative study with parents
from multi-ethnic backgrounds living in England.
AB - BACKGROUND: Guidelines recommend children and young people participate in at
least 60 min of physical activity (PA) every day, however, findings from UK
studies show PA levels of children vary across ethnic groups. Since parents play
an instrumental role in determining children's PA levels, this article aims to
explore parental views of children's PA in a multi-ethnic sample living in a
large city in the North-West of England. METHODS: Six single-ethnic focus groups
were conducted with 36 parents of school-aged children (4 to 16 years) with a
predominantly low socio-economic status (SES). Parents self-identified their
ethnic background as Asian Bangladeshi (n = 5), Black African (n = 4), Black
Somali (n = 7), Chinese (n = 6), White British (n = 8) and Yemeni (n = 6). Focus
group topics included understanding of PA, awareness of PA guidelines, knowledge
of benefits associated with PA and perceived influences on PA in childhood. Data
were analysed thematically using QSR NVivo 9.0. RESULTS: Parents from all ethnic
groups valued PA and were aware of its benefits, however they lacked awareness of
PA recommendations, perceived school to be the main provider for children's PA,
and reported challenges in motivating children to be active. At the environmental
level, barriers to PA included safety concerns, adverse weather, lack of
resources and lack of access. Additional barriers were noted for ethnic groups
from cultures that prioritised educational attainment over PA (Asian Bangladeshi,
Chinese, Yemeni) and with a Muslim faith (Asian Bangladeshi, Black Somali,
Yemeni), who reported a lack of culturally appropriate PA opportunities for
girls. CONCLUSION: Parents from multi-ethnic groups lacked awareness of
children's PA recommendations and faced barriers to promoting children's PA out
of school, with certain ethnic groups facing additional barriers due to cultural
and religious factors. It is recommended children's PA interventions address
influences at all socio-ecological levels, and account for differences between
ethnic groups.
PMID- 26431699
TI - The North Atlantic Oscillation system and plant phenology.
AB - The onset of flowering in 78 wild and domesticated terrestrial plant species
recorded in South Moravia (Czech Republic) from 1965 to 2014 was correlated with
the North Atlantic Oscillation (NAO) index of the preceding winter. Flowering
occurred significantly earlier following positive winter NAO phases (causing
spring to be warmer than normal in Central Europe) in nearly all early-flowering
(March, April) species; high Pearson correlation values were recorded in, e.g.,
goat willow, spring snowflake, golden bell, cornelian cherry, sweet violet,
cherry plum, grape hyacinth, apricot, blackthorn, common dandelion, cherry,
southern magnolia, common apple, cuckoo flower, European bird cherry, and cherry
laurel. In contrast, the timing of later-flowering plant species (May to July)
did not correlate significantly with the winter NAO index. It was found that
local temperature is obviously a proximate factor of plant phenology, while the
winter NAO is the ultimate factor, affecting temperature and other meteorological
phenomena in Central Europe during spring season.
PMID- 26431698
TI - The Impact of Bariatric Surgery on Polycystic Ovary Syndrome: a Systematic Review
and Meta-analysis.
AB - Bariatric surgery has been proven to be a successful management strategy for
morbid obesity, but limited studies exist on its effect on polycystic ovary
syndrome (PCOS). A comprehensive search of electronic databases was completed.
Meta-analysis was performed on PCOS, hirsutism, and menstrual irregularity
outcomes following bariatric surgery. Thirteen primary studies involving a total
of 2130 female patients were identified. The incidence of PCOS preoperatively was
45.6 %, which significantly decreased to 6.8 % (P < 0.001) and 7.1 % (P < 0.0002)
at 12-month follow-up and study endpoint, respectively. The incidences of
preoperative menstrual irregularity and hirsutism both significantly decreased at
12-month and at study end follow-up. Bariatric surgery effectively attenuates
PCOS and its clinical symptomatology including hirsutism and menstrual
irregularity in severely obese women.
PMID- 26431700
TI - Diurnal variations of airborne pollen concentration and the effect of ambient
temperature in three sites of Mexico City.
AB - Pollen is an important cause of allergic respiratory ailments in the Mexico City
Metropolitan Area (MCMA). However, very little is known if ambient air
temperature correlates with the early blooming of plants observed in other urban
areas around the world. A research study was conducted during the dry season of
2012-2013 at three representative sites of the MCMA with different urban
characteristics with the aim to understand the relationships between the
profusion and diversity of pollen against temperature and other meteorological
variables and degree of urbanization. Pollen samples were collected using a Hirst
type trap sampler in the sites: Merced (highly urbanized), Iztapalapa (medium
high urbanized) and Coyoacan (moderately urbanized). Urbanization levels were
determined using a composite index based on population density, proportion of
surface covered by construction and asphalt, and urban heat island intensity. A
set of representative pollen sampling tapes were assayed under a light microscope
at magnification of *1,000 and converted to grains per cubic meter. The most
representative pollen types found in the three sites were, regardless of
urbanization levels were: Fraxinus, Cupressaceae/Taxodiaceae, Casuarina, Alnus,
Myrtaceae, and Pinus. Total pollen concentration was greatest in the moderately
urbanized area, although earlier blooming took place at the highly urbanized
zone. Total pollen concentration in the medium-high urbanized site has the lowest
because the green areas in this zone of MCMA are few. In a diurnal basis, the
most abundant pollen types peaked near midday or in the afternoon evening at the
three sites. A Spearman test showed a positive correlation among bihourly pollen
concentrations, temperature and relative humidity in all sites, but wind speed
just correlated in Iztapalapa and Coyoacan. The results obtained suggest that
Urban Heat Island Intensity can disturb flowering periods and pollen
concentrations, largely in the highly urbanized areas. A principal components
analysis established that the concentrations of each pollen type differed across
the urbanization gradients. Additionally, it was found that a large number of
allergenic pollens are produced by ornamental trees, some only recently
introduced by urban planners.
PMID- 26431701
TI - The effects of different levels of Chlorella microalgae on blood biochemical
parameters and trace mineral concentrations of laying hens reared under heat
stress condition.
AB - This study was conducted to investigate the effect of different supplementation
levels of Chlorella microalgae on serum metabolites and the plasma content of
minerals in laying hens reared under heat stress condition (27.5-36.7 degrees C,
variable). A total number of 378 (40 weeks of age, with mean body weight of 1390
+/- 120 g) were randomly allocated to six treatments with seven replicates. The
birds were randomly assigned to 6 treatments (C, T1, T2, T3, T4, and T5) with 7
replicate cages of 9 birds. C. microalgae at the rates of 100, 200, 300, 400, and
500 ppm with water were offered to groups T1, T2, T3, T4, and T5, respectively,
while group C served as a control. At 71 days of trial, blood samples (14 samples
per treatment) were taken for measuring serum metabolites and at 72 days for
plasma mineral analysis. The results of this experiment showed that the
supplementation of 200-500 ppm C. microalgae decreased the serum content of
cholesterol, triglycerides, and LDL (P < 0.05) whereas HDL content increased (P <
0.05) in the hens supplemented with C. microalgae (300 or 400 and 500 ppm). C.
microalgae at rates of 300-500 ppm caused a marked (P < 0.05) increase in the
plasma content of manganese or iodine and selenium but other minerals were not
statistically different among treatments. Overall, from the results of the
present experiment, it can be concluded that supplementation of C. microalgae at
high rates was beneficial on blood parameters of laying hens reared under heat
stress.
PMID- 26431702
TI - Meniscus transplantation.
AB - Understanding the structure and function of the meniscus is critical to
understanding its role in overall knee joint function. Injury to, or removal of,
meniscal tissue may be associated with articular cartilage wear, knee
instability, and, ultimately, the progression of osteoarthritis. While every
effort is made for preserving and/or repairing damaged meniscal tissue, in some
cases, the meniscus is not amenable to repair after injury. For appropriately
indicated patients with symptomatic meniscal deficiency, meniscus allograft
transplantation is an excellent surgical solution aimed at reducing pain and
improving function. Indications for meniscus allograft transplantation are
limited, and concomitant procedures such as osteotomy for malalignment,
ligamentous, and/or articular cartilage restoration may be necessary in order to
ensure an optimal result following meniscus allograft transplantation. Surgical
techniques for meniscus allograft transplantation are variable and include soft
tissue fixation versus bone plug fixation versus bone bridge fixation. Outcomes
following meniscus allograft transplantation are generally good to excellent,
though reoperation rates are relatively high. The purpose of this article is to
provide a concise review of recently published data on meniscus allograft
transplantation, with a focus on recent outcomes studies.
PMID- 26431703
TI - Transgenic Cotton-Fed Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) Affects
the Parasitoid Encarsia desantisi Viggiani (Hymenoptera: Aphelinidae)
Development.
AB - Cotton cultivars expressing Cry proteins are widely used to control lepidopteran
pests. The effects of transgenic plants containing insecticidal Cry proteins on
non-target species must be comprehended for a better and rational use of this
technology for pest management. We investigated the influence of the Bt cotton
cultivars NuOPAL and FM 975 on biological parameters of Bemisia tabaci
(Gennadius) (Hemiptera: Aleyrodidae), a non-target pest of Bt cotton cultivars
and on its parasitoid Encarsia desantisi Viggiani (Hymenoptera: Aphelinidae). The
experiments were conducted in a climatized room, and the non-transgenic near
isolines were used for rearing whiteflies as control hosts. The effects of the Bt
cotton cultivars on the period of embryonic and larval development and the
percentage of adult emergence of B. tabaci were assessed. The period required for
embryonic, larval, and pupal development and the percentage of emergence and
longevity of E. desantisi females were determined using Bt cotton-fed and non-Bt
cotton-fed B. tabaci as hosts. Both Bt cotton cultivars resulted in a decrease of
approximately 20% of adult emergence of B. tabaci. Differently, an increase of
approximately 10% of adult emergence of E. desantisi was observed for parasitoids
that used hosts fed with both Bt cotton cultivars. However, female parasitoid
longevity decreased when their hosts were fed on Bt cotton cultivars. Our data
suggest that the use of Bt cotton cultivars in association with the biological
control agent E. desantisi could be functional for the management of B. tabaci in
Bt cotton crops.
PMID- 26431704
TI - Heavy metal concentrations and enzymatic activities in the functional zone
sediments of Haizhou Bay, Lianyungang, Jiangsu, China.
AB - Surface sediments were collected at 31 sites covering five functional zones of
Haizhou Bay, Lianyungang, Jiangsu, China. Heavy metal concentrations and
enzymatic activity of phosphatase and urease were determined on a dry-weight
basis of sediments. Metal concentrations in sediments were comparable to the
Chinese National Standard of Marine Sediment Quality and were as follows: Cu,
8.60-55.8 mg kg(-1); Zn, 107-384 mg kg(-1); Pb, 33.6-200 mg kg(-1); Cd, 0.24-2.57
mg kg(-1); Cr, 30.3-92.1 mg kg(-1); As, 12.9-110 mg kg(-1); Ni, 15.8-49.6 mg kg(
1); Mn, 379-1272 mg kg(-1); and Fe, 13,790-38,240 mg kg(-1). A geoaccumulation
index (I geo) was calculated to help researchers understand the status of
pollutants in the sediments. I geo showed that Cd and As contamination existed in
the study area. The mobility of the metals and the relationship between heavy
metal concentrations of chemical fractions and enzymatic activities were also
investigated. Results showed that Cd and Mn had higher mobility than other
metals, and enzymatic activities may play an important role in controlling the
bioavailability and transformation trend of heavy metals from one fraction to
another in sediments.
PMID- 26431705
TI - Arsenic levels in immigrant children from countries at risk of consuming arsenic
polluted water compared to children from Barcelona.
AB - Arsenic is a highly toxic element that pollutes groundwater, being a major
environmental problem worldwide, especially in the Bengal Basin. About 40% of
patients in our outpatient clinics come from those countries, and there is no
published data about their arsenic exposure. This study compares arsenic exposure
between immigrant and native children. A total of 114 children (57 natives, 57
immigrants), aged 2 months to 16 years, were recruited and sociodemographic and
environmental exposure data were recorded. Total arsenic in urine, hair, and
nails and arsenic-speciated compounds in urine were determined. We did not find
significant differences in total and inorganic arsenic levels in urine and hair,
but in organic arsenic monomethylarsenic acid (MMA) and dimethylarsinous acid
(DMA) in urine and in total arsenic in nails. However, these values were not in
the toxic range. There were significant differences between longer than 5 years
exposure and less than 5 years exposure (consumption of water from tube wells),
with respect to inorganic and organic MMA arsenic in urine and total arsenic in
nails. There was partial correlation between the duration of exposure and
inorganic arsenic levels in urine. Immigrant children have higher arsenic levels
than native children, but they are not toxic. At present, there is no need for
specific arsenic screening or follow-up in immigrant children recently arrived in
Spain from exposure high-risk countries.
PMID- 26431706
TI - Seasonal and spatial evolution of trihalomethanes in a drinking water
distribution system according to the treatment process.
AB - This paper comparatively shows the influence of four water treatment processes on
the formation of trihalomethanes (THMs) in a water distribution system. The study
was performed from February 2005 to January 2012 with analytical data of 600
samples taken in Aljaraque water treatment plant (WTP) and 16 locations along the
water distribution system (WDS) in the region of Andevalo and the coast of Huelva
(southwest Spain), a region with significant seasonal and population changes. The
comparison of results in the four different processes studied indicated a clear
link of the treatment process with the formation of THM along the WDS. The most
effective treatment process is preozonation and activated carbon filtration (P3),
which is also the most stable under summer temperatures. Experiments also show
low levels of THMs with the conventional process of preoxidation with potassium
permanganate (P4), delaying the chlorination to the end of the WTP; however, this
simple and economical treatment process is less effective and less stable than
P3. In this study, strong seasonal variations were obtained (increase of THM from
winter to summer of 1.17 to 1.85 times) and a strong spatial variation (1.1 to
1.7 times from WTP to end points of WDS) which largely depends on the treatment
process applied. There was also a strong correlation between THM levels and water
temperature, contact time and pH. On the other hand, it was found that THM
formation is not proportional to the applied chlorine dose in the treatment
process, but there is a direct relationship with the accumulated dose of
chlorine. Finally, predictive models based on multiple linear regressions are
proposed for each treatment process.
PMID- 26431707
TI - Endovascular treatment of complex aortic aneurysms: prevalence of acute kidney
injury and effect on long-term renal function.
AB - OBJECTIVES: To analyse predictors for short- and long-term renal function changes
after fenestrated and branched endovascular aortic repair (EVAR). METHODS: A
total of 157 patients underwent fenestrated and branched EVAR. Procedural intra
arterial iodinated contrast volume was documented. Serum creatinine and estimated
glomerular filtration rate (eGFR) at baseline, during 48 h following EVAR, at
discharge and latest moment of follow-up were recorded. Development of post-EVAR
acute kidney injury (AKI; according to AKIN criteria), and potential risk factors
for renal failure were recorded. Multivariate regression analyses were used to
identify independent risk factors for AKI and eGFR decrease during follow-up.
RESULTS: Forty-three patients (28 %) developed post-EVAR AKI. Long procedure time
and occlusion of accessory renal arteries were independent risk factors for
development of AKI. (odds ratio (OR) 1.005 per minute, 95 % CI 1.001-1.01; p =
0.025 and OR 3.02, 95 % CI 1.19-8.16; p = 0.029). Post-EVAR AKI was associated
with a significantly increased risk for eGFR decrease at discharge and latest
follow-up (hazard ratio (HR) 3.47, 95 % CI 1.63-7.36, p = 0.001 and HR 3.01, 95 %
CI 1.56-5.80; p = 0.001). Iodinated contrast volume was not an independent risk
factor for AKI or eGFR decrease during follow-up. CONCLUSION: Development of post
EVAR AKI is an independent risk factor for long-term renal function decrease. KEY
POINTS: * Longer procedure time is associated with an increased risk for AKI. *
Renal perfusion defects on angiography are associated with increased risk for
AKI. * Post-EVAR AKI is associated with higher probability for long-term eGFR
decrease. * Iodinated contrast volume is not an independent risk factor for AKI.
* Iodinated contrast volume is not an independent risk factor for long-term eGFR
decrease.
PMID- 26431708
TI - Safety and efficiency of femoral artery access closure with a novel biodegradable
closure device: a prospective single-centre pilot study.
AB - OBJECTIVES: Vascular closure devices can accelerate haemostasis after
arteriotomy, but induce scarring. The aim of the study was to prospectively
analyse the feasibility of a novel biodegradable arterial closure device (CD).
METHODS: Two hundred fifty-five patients (183 male; age 36-98 years) with an
access vessel diameter >3 mm received the biodegradable CD after endovascular
therapy. Technical success rate, time-to-haemostasis (TTH) and time-to-ambulation
(TTA) were measured. Puncture site complications were categorized as minor (local
hematoma, minor bleeding) or major (pseudoaneurysm, embolization, dissection,
thrombotic occlusion, hematoma/major bleeding requiring surgery, access site
infection). RESULTS: Technical success was achieved in 98.8 % (252 cases); device
failure occurred in three cases (1.2 %). The average TTH and TTA were 11.3 +/-
26.9 s and 73.0 +/- 126.3 min. The major complication rate was 1.6 %, with three
pseudoaneurysms and one retroperitoneal bleeding. The minor complication rate was
2.0 %, with five small hematomas. Neither cardiovascular risk factors nor access
vessel characteristics had statistically significant influence on adverse events.
Re-puncture was uncomplicated in 32 cases after 155.0 +/- 128.8 days.
CONCLUSIONS: Handling of the new biodegradable CD is safe. The complication rates
are tolerably low and comparable to other CDs. Post-procedural sonography showed
no significant palpable subcutaneous changes in the access site. KEY POINTS: *
VCDs can increase time efficiency and patient comfort after intervention. * In
this prospective single-centre-study, biodegradable CD was safe and easily
applicable. * Its major and minor complication rates are comparable to other CDs.
* Its mean time-to-haemostasis and time-to-ambulation were 11.3 +/- 26.9 s and
73.0 +/- 126.3 min. * Post-procedural sonography showed no significant palpable
subcutaneous changes at the access site.
PMID- 26431709
TI - Energy and protein requirements of non-descript breed hair lambs of different sex
classes in the semiarid region of Brazil.
AB - The aim of this study was to determine the energy and protein requirements of non
descript breed hair lambs (NDB) reared under Brazilian semiarid conditions. Sixty
animals from three sex classes (20 intact males, 20 castrated males, and 20
females) with an average initial body weight of 18.1 +/- 0.4 kg and an average
age of 5 months were used. The nutritional requirements were estimated using the
comparative slaughter. The animals in the final slaughter group were distributed
in a completely randomized design with a 3 * 3 factorial scheme (three sex
classes and three feeding levels: ad libitum feeding (positive energy balance),
70% feed restriction (maintenance level), and 80% feed restriction (negative
energy balance)). The net energy requirement for maintenance (NEm) did not differ
between sex classes (P > 0.05) and it was 68 kcal/kg of metabolic empty body
weight (EBW(0.75))/day (P < 0.05). The coefficients for the nonlinear regression
of retained energy (RE) on the empty body weight gain (EBWG) were not different
among the different sex classes (P > 0.05). The net energy requirement for weight
gain (NEg) was estimated by NEg (Mcal/day) = 0.29 * EBW(0.75) * EBWG(0.86) for
all sex classes (P < 0.05). The net protein requirement for weight gain (NPg) was
estimated by NPg (g/day) = 224.45 * EBWG - 0.025 * RE for all sex classes (P <
0.05). The NEg increased and the NPg decreased with the increase in body weight
of NDB lambs.
PMID- 26431710
TI - Weight gain potential affects pregnancy rates in bovine embryo recipients raised
under pasture conditions.
AB - The aim of the present study was to evaluate the effect of differences in body
weight gain after embryo transfer on the pregnancy rates of crossbred heifers
used as recipients and raised under a grazing system. The study was performed
during the dry (April to September) and the rainy (October to March) seasons. The
embryos transferred were produced by in vitro fertilization. The body weight of
each recipient was measured immediately before the embryo transfer and 23 to 25
days later, when the diagnosis of pregnancy was performed by ultrasonography. The
associations among initial body weight (IBW), daily body weight gain (DWG),
season, and pregnancy rate were evaluated using a logistic procedure that
included the effect of the IBW, season, and linear and quadratic effects of the
DWG. Altogether, there was no effect of season and pregnancy rates did not change
between the dry and rainy seasons (42.3 vs. 45.8%, respectively; P > 0.05).
However, the pregnancy rate was greater in the recipients with daily body weight
gains over 250 g/day, regardless of the season. In addition, the pregnancy rate
of the recipients was better (P < 0.04) explained by a logistic regression model
that included the linear and quadratic effects of the DWG. The probability of
each heifer to become pregnant according to DWG is explained by the follow
equation: P(y = 1) = (Exp((-1.06703 + 0.0108 * DWG - 0.00002 * DWG ^ 2)))/(1 +
Exp((-1.6703 + 0.0108 * DWG - 0.00002 * DWG ^ 2))). In conclusion, body weight
gain potential is a critical factor for the pregnancy rates of in vitro embryo
recipients managed under grazing systems.
PMID- 26431713
TI - Mentally ill man should not be forced to have foot amputation, judge rules.
PMID- 26431711
TI - Effects of live weight at slaughter on fatty acid composition of Longissimus
dorsi and Biceps femoris muscles of indigenous Lori goat.
AB - This study aimed to determine fatty acid (FA) composition of Longissimus dorsi
(LD) and Biceps femoris (BF) muscles of an Iranian indigenous goat (Lori goat) at
two live weights at slaughter (LWS). Twenty male Lori goats (5 to 8 months)
raised in nomadic system were slaughtered either at LWS less than 20 kg (light)
or LWS more than 30 kg (heavy). Carcass dressing and FA composition of
intramuscular fat of LD and BF muscles as well as cholesterol content of LD
muscle were determined. Heavy goats had higher dressing percentage than light
ones (42.7vs.39.3%, P < 0.01). The predominant n-6 FA were C18:2, and C20:4 while
C22:5, C20:5, C18:3, C20:3, and C22:6 were the n-3 FA detected. Polyunsaturated
and saturated FA contributed 22% and 36% of the total FA in both muscles,
respectively. Palmitic acid (C16:0) of LD was higher in heavy compared to the
light goats (P < 0.05). BF muscle had higher alpha-linolenic acid (18:3 n-3) as
percentage than LD muscle (P < 0.05). The ratio of n-6/n-3 FA and
polyunsaturated/saturated FA were 3.8 and 0.6, respectively. Cholesterol content
of LD muscle of light and heavy goats were 71.2 +/- 16 and 59.5 +/- 14 mg per 100
g fresh meat respectively. In conclusion, desirable PUFA/SFA (0.6) and n-3/n-6
ratio (3.8) found in indigenous Lori goat propose healthy source of lean meat for
the consumers.
PMID- 26431712
TI - Ingestive behavior and physiological parameters of goats fed diets containing
peanut cake from biodiesel.
AB - The experiment was conducted to evaluate the ingestive behavior and physiological
parameters of confined goats fed peanut cake instead of soybean meal in their
feed. We used 40 goats that were 3/4 Boer, uncastrated, and 5 months of age on
average, with an average initial weight of 15.6 +/- 2.7 kg. The treatments
consisted of diets with different levels of peanut cake replacing soybean meal in
the concentrate (0.0, 33.33, 66.67, and 100%). The experimental design was
completely randomized, with four treatments and ten repetitions. For the
evaluation of feeding behavior, single animals were observed every 5 min for 24 h
on 3 days. The physiological responses (respiratory rate; heart rate; rectal
temperature, obtained with a rectal thermometer; and surface temperature) of the
animals were evaluated at 09:00 and 15:00 h. The replacement of soybean meal with
peanut cake did not change (P > 0.05) feeding behavior. The physiological
parameters of the animals (P < 0.05) were altered; however, the changes appeared
to be unrelated to the diet and to be due to the weather conditions. Peanut cake
can replace soybean meal at 100% without causing negative effects on the feeding
behavior or physiological parameters of confined 3/4 Boer goats.
PMID- 26431714
TI - Functional Characterization of Carrier-Mediated Transport of Pravastatin across
the Blood-Retinal Barrier in Rats.
AB - Systemically administered pravastatin effectively treats diabetic retinopathy
without central nervous system side effects. The efflux transport mechanism of
pravastatin from the brain has already been clarified. In this study, the influx
of pravastatin across the blood-retinal and blood-brain barriers (BRB and BBB)
and the efflux of pravastatin from the retina were investigated using rats.
Pravastatin influx (blood-to-tissues) was assessed using the retinal and brain
uptake index (RUI and BUI) methods, and microdialysis was performed to
investigate the efflux (retina-to-blood) transport of pravastatin. The RUI and
BUI values for [(3)H]pravastatin were lower than those expected based on its
lipophilicity, suggesting that the influx transport across the BRB and BBB was
less than the reverse-direction transport. The RUI and BUI values for
[(3)H]pravastatin were significantly decreased by pravastatin, digoxin, and
probenecid, indicating that pravastatin undergoes carrier-mediated influx
transport in the blood-to-tissues direction across the BRB and BBB. After
intravitreal injection, [(3)H]pravastatin and the bulk flow marker [(14)C]d
mannitol were found to be eliminated biexponentially from the vitreous humor. The
elimination rate constant of [(3)H]pravastatin during the terminal phase was 1.66
fold greater than that of [(14)C]d-mannitol. Efflux transport was reduced in the
retinal presence of pravastatin, digoxin, and benzylpenicillin, suggesting that
pravastatin is transported via efflux transporters. In conclusion, pravastatin is
transported across the BRB via uptake and efflux transporters in both the blood
to-retina and retina-to-blood directions, and the retina-to-blood transporters
are dominant, based on the lower values of the RUI compared with the values
expected from the lipophilicity.
PMID- 26431715
TI - To feed or not to feed?
PMID- 26431716
TI - Prebiotics: why definitions matter.
AB - The prebiotic concept was introduced twenty years ago, and despite several
revisions to the original definition, the scientific community has continued to
debate what it means to be a prebiotic. How prebiotics are defined is important
not only for the scientific community, but also for regulatory agencies, the food
industry, consumers and healthcare professionals. Recent developments in
community-wide sequencing and glycomics have revealed that more complex
interactions occur between putative prebiotic substrates and the gut microbiota
than previously considered. A consensus among scientists on the most appropriate
definition of a prebiotic is necessary to enable continued use of the term.
PMID- 26431717
TI - Microbial oils as food additives: recent approaches for improving microbial oil
production and its polyunsaturated fatty acid content.
AB - In this short review, we summarize the latest research in the production of
polyunsaturated microbial oils that are of interest in food technology. The
current research targets the productivity of oleaginous microorganisms, as well
as the biosynthesis of particular polyunsaturated fatty acids (PUFAs). The most
important efforts target the efficiency of the oleaginous machinery, via
overexpression of key-enzymes involved in lipid biosynthesis, as well as the
minimization of lipid degradation, by repressing genes involved in the beta
oxidation pathway. The production of specific PUFAs is approached by homologous
or heterologous expression of specific desaturases and elongases involved in PUFA
biosynthesis in oleaginous microorganisms. New perspectives, such as the
production of triacylglycerols of specific structure and the employment of
adaptive experimental evolution for creating robust oleaginous strains able to
produce PUFAs are also discussed.
PMID- 26431719
TI - Adjunctive therapy with inhaled nitric oxide for severe acute chest syndrome in
patients with sickle cell disease.
PMID- 26431718
TI - Inhaled nitric oxide for acute chest syndrome in adult sickle cell patients: a
randomized controlled study.
AB - PURPOSE: Previous clinical trials suggested that inhaled nitric oxide (iNO) could
have beneficial effects in sickle cell disease (SCD) patients with acute chest
syndrome (ACS). METHODS: To determine whether iNO reduces treatment failure rate
in adult patients with ACS, we conducted a prospective, double-blind, randomized,
placebo-controlled clinical trial. iNO (80 ppm, N = 50) gas or inhaled nitrogen
placebo (N = 50) was delivered for 3 days. The primary end point was the number
of patients with treatment failure at day 3, defined as any one of the following:
(1) death from any cause, (2) need for endotracheal intubation, (3) decrease of
PaO2/FiO2 >= 15 mmHg between days 1 and 3, (4) augmented therapy defined as new
transfusion or phlebotomy. RESULTS: The two groups did not differ in age, gender,
genotype, or baseline characteristics and biological parameters. iNO was well
tolerated, although a transient decrease in nitric oxide concentration was
mandated in one patient. There was no significant difference in the primary end
point between the iNO and placebo groups [23 (46 %) and 29 (58 %); odds ratio
(OR), 0.8; 95 % CI, 0.54-1.16; p = 0.23]. A post hoc analysis of the 45 patients
with hypoxemia showed that those in the iNO group were less likely to experience
treatment failure at day 3 [7 (33.3 %) vs 18 (72 %); OR = 0.19; 95 % CI, 0.06
0.68; p = 0.009]. CONCLUSIONS: iNO did not reduce the rate of treatment failure
in adult SCD patients with mild to moderate ACS. Future trials should target more
severely ill ACS patients with hypoxemia. CLINICAL TRIAL REGISTRATION:
NCT00748423.
PMID- 26431722
TI - [Strategic considerations on the design and choice of animal models for non
clinical investigations of cell-based medicinal products].
AB - For the development of medicinal products animal models are still indispensable
to demonstrate efficacy and safety prior to first use in humans. Advanced therapy
medicinal products (ATMP), which include cell-based medicinal products (CBMP),
differ in their pharmacology and toxicology compared to conventional
pharmaceuticals, and thus, require an adapted regime for non-clinical
development. Developers are, therefore, challenged to develop particular
individual concepts and to reconcile these with regulatory agencies. Guidelines
issued by the European Medicines Agency (EMA), the U.S. Food and Drug
Administration (FDA) and other sources can provide direction.The published
approaches for non-clinical testing of efficacy document that homologous animal
models where the therapeutic effect is investigated in a disease-relevant animal
model utilizing cells derived from the same species are commonly used. The
challenge is that the selected model should reflect the human disease in all
critical features and that the cells should be comparable to the investigated
human medicinal product in terms of quality and biological activity. This is not
achievable in all cases. In these cases, alternative methods may provide
supplemental information. To demonstrate the scientific proof-of-concept (PoC),
small animal models such as mice or rats are preferred. During the subsequent
product development phase, large animal models (i.e. sheep, minipigs, dogs) must
be considered, as they may better reflect the anatomical or physiological
situation in humans. In addition to efficacy, those models may also be suitable
to prove some safety aspects of ATMP (e.g. regarding dose finding, local
tolerance, or undesired interactions and effects of the administered cells in the
target tissue). In contrast, for evaluation of the two prominent endpoints for
characterizing the safety of ATMP (i.e. biodistribution, tumorigenicity)
heterologous small animal models, especially immunodeficient mouse strains, are
favourable due to their tolerance to the human cell therapy product. The
execution of non-clinical studies under the principles of good laboratory
practice (GLP) increases the acceptance of the results by authorities and the
scientific community.
PMID- 26431720
TI - Very high volume hemofiltration with the Cascade system in septic shock patients.
AB - PURPOSE: We compared hemodynamic and biological effects of the Cascade system,
which uses very high volume hemofiltration (HVHF) (120 mL kg(-1) h(-1)), with
those of usual care in patients with septic shock. METHODS: Multicenter,
prospective, randomized, open-label trial in three intensive care units (ICU).
Adults with septic shock with administration of epinephrine/norepinephrine were
eligible. Patients were randomized to usual care plus HVHF (Cascade group), or
usual care alone (control group). Primary end point was the number of
catecholamine-free days up to 28 days after randomization. Secondary end points
were number of days free of mechanical ventilation, renal replacement therapy
(RRT) or ICU up to 90 days, and 7-, 28-, and 90-day mortality. RESULTS: We
included 60 patients (29 Cascade, 31 usual care). Baseline characteristics were
comparable. Median number of catecholamine-free days was 22 [IQR 11-23] vs 20 [0
25] for Cascade vs control; there was no significant difference even after
adjustment. There was no significant difference in number of mechanical
ventilation-free days or ICU requirement. Median number of RRT-free days was 85
[46-90] vs 74 [0-90] for Cascade vs control groups, p = 0.42. By multivariate
analysis, the number of RRT-free days was significantly higher in the Cascade
group (up to 25 days higher after adjustment). There was no difference in
mortality at 7, 28, or 90 days. CONCLUSION: Very HVHF using the Cascade system
can safely be used in patients presenting with septic shock, but it was not
associated with a reduction in the need for catecholamines during the first 28
days.
PMID- 26431723
TI - [Effect of autologous platelet concentrates on the anatomical and functional
outcome of late stage macular hole surgery: A retrospective analysis].
AB - BACKGROUND: The macular hole (MH) is a disorder of the visual center of the
retina in humans. An untreated MH leads to loss of central visual acuity and
reading ability. Surgery for early-stage macular holes has been very successful
for many years and leads to very good anatomical and functional results. Despite
continuous improvement of surgical procedures, the outcome for the later stages
of MH is still unsatisfactory. METHOD: In a retrospective analysis, we
investigated the effect of autologous platelet concentrates in patients
presenting later stages of MHs (stage III-IV) with respect to anatomic success
(hole closure) and recovery of vision. The application of platelets was performed
during retinal surgery (pars plana vitrectomy, ppV). In addition, selected
platelet concentrates were qualitatively analysed for growth factors and platelet
adhesion. RESULTS: In the first group, 74% of the patients showed a good
anatomical macular hole closure. The analyses of the platelet concentrates
indicated a possible wound-healing effect due to growth factors (e.g. the
platelet-derived growth factor, PDGF) and lesser to the ability of the platelets
to adhere after ristocetin administration. Further optimization of the production
process of platelet concentrates and of the surgical procedure in the second
group of patients showed an increase of the anatomical success (92%) and a very
rapid increase of visual acuity within six weeks. DISCUSSION: In the past, the
primary goal of MH surgery was to optimize the surgical procedures. Only few
concepts focused on wound healing. Based on our data, we postulate the use of
autologous platelet concentrates in MH surgery as a healing concept, which helps
to increase the functional success of late-stage macular hole surgery.
PMID- 26431724
TI - Gender aspects of recreational sun-protective behavior: results of a
representative, population-based survey among Austrian residents.
AB - PURPOSE: Lifetime risk for melanoma skin cancer is enlarged by sunlight exposure
and reduced by sun protection. Austrian melanoma incidence and mortality rates
are constantly rising with higher rates in males. Thus, we aimed at investigating
gender-specific recreational sun exposure habits among the Austrian population.
METHODS: We conducted a telephone survey among 1500 adults (50.5% females)
representing sociodemographic characteristics of the Austrian population. Using a
structured questionnaire, we studied gender-specific sun exposure-related
knowledge, motives to tan, and behavior. RESULTS: Overall, using sunscreen,
wearing sunglasses, and seeking shade were among the three most frequent sun safe
measures. Basic skin health knowledge and tanning motives were similar among
genders, although females protected themselves more. In general, sunburn
occurrence (odds ratio [OR] = 1.4, 95% confidence interval [CI] = 1.0-1.8), skin
type IV (OR = 2.4, 95% CI = 1.3-4.5), ex-/non-smoking (OR = 1.4-1.6, 95% CI = 1.0
2.1), low motives to tan (both OR = 1.3, 95% CI = 1.0-1.7), no outdoor sport (OR
= 1.3, 95% CI = 1.0-1.7), all P < 0.05, as well as the use of sunscreen with
lower SPF values (OR = 1.0-3.0, 95% CI = 1.4-4.3) and male gender (OR = 1.6, 95%
CI = 1.2-2.0), both P < 0.001, increased the odds of practicing low sun
protection. CONCLUSION: The results of this investigation suggest considering
gender specificity when planning Public (Skin) Health-related educative campaigns
and programs, for example, by highlighting the appearance-related benefits of sun
light avoidance.
PMID- 26431725
TI - Halomonas salicampi sp. nov., a halotolerant and alkalitolerant bacterium
isolated from a saltern soil.
AB - A Gram-stain-negative, halotolerant and alkalitolerant bacterium, designated
strain BH103T, was isolated from saltern soil in Gomso, Korea. Cells of strain
BH103T were strictly aerobic, motile, straight rods and grew at pH 7.0-10.8
(optimum, pH 8.5), at 10-55 degrees C (optimum, 28 degrees C) and at salinities
of 0-23 % (w/v) NaCl (optimum, 14 % NaCl). Phylogenetic analyses based on 16S
rRNA gene sequences indicated that strain BH103T belongs to the genus Halomonas,
showing highest sequence similarity to Halomonas boliviensis LC1T (97.7 %),
Halomonas neptunia Eplume1T (97.7 %), Halomonas variabilis IIIT (97.7 %),
Halomonas alkaliantarctica CRSST (97.7 %), Halomonas olivaria TYRC17T (97.5 %),
Halomonas titanicae BH1T (97.2 %) and Halomonas sulfidaeris Esulfide1T (96.2 %).
The predominant ubiquinone was Q-9. The major fatty acids were C18 : 1omega7c,
C16 : 1omega7c and/or iso-C15 : 0 2-OH, C16 : 0 and C12 : 0 3-OH. The major polar
lipids were phosphatidylglycerol, diphosphatidylglycerol,
phosphatidylethanolamine, aminophospholipid and an unknown phospholipid. The DNA
G+C content of this novel isolate was 54.7 mol%. DNA-DNA relatedness between
strain BH103T and H. boliviensis KACC 16615T, H. neptunia KCTC 2888T, H.
variabilis KCTC 2889T, H. alkaliantarctica KCTC 22844T, H. olivaria DSM 19074T,
H. titanicae JCM 16411T and H. sulfidaeris DSM 15722T was 45, 41, 39, 32, 38, 45
and 35 %, respectively. On the basis of polyphasic analysis from this study,
strain BH103T represents a novel species of the genus Halomonas, for which the
name Halomonas salicampi sp. nov. is proposed. The type strain is BH103T ( = KACC
17609T = NBRC 109914T = NCAIM B 02528T).
PMID- 26431726
TI - Perspective: Medical Malpractice Roller Coaster.
PMID- 26431727
TI - In Reply to the Letter to the Editor, "3-Dimensional Printing Rapid Prototyping
for Intracranial Aneurysm Coiling: A Good Example of Precise Medicine".
PMID- 26431728
TI - Postoperative Visual Loss After Spine Surgery and the Role of the Neurosurgeon.
PMID- 26431729
TI - Medical Malpractice and Hollywood: Liability Magnified by the Lens of Celebrity.
PMID- 26431730
TI - PIPA, RISA, ATPA & Co.: The Efforts We Spent on Convincing Others to Do the Best
for our Patients with Petroclival Meningiomas.
PMID- 26431731
TI - Technical Description of the Medial and Lateral Anterior Temporal Approach for
the Treatment of Complex Proximal Posterior Cerebral Artery Aneurysms.
AB - BACKGROUND: Posterior cerebral artery (PCA) aneurysms are often fusiform and
associated with multiple intracranial aneurysms. A bypass procedure in
combination with proximal occlusion or aneurysm trapping is considered to be
effective for the treatment of patients with complex PCA aneurysms. Because of
the deep, narrowed surgical corridor and the surrounding sensitive neuroanatomic
structures, microsurgical procedures applied to the PCA are technically
demanding. The authors present a technical report of a complex aneurysm formation
located at the postcommunicating segment of the PCA (PCA-P2) treated via an
anterior temporal approach. METHODS: A 68-year-old woman had an unruptured PCA-P2
aneurysm formation, which was discovered incidentally. The fusiform aneurysm
shape of the distal aneurysm aggravated direct microsurgical and endovascular
treatment. After an individual case discussion, the patient underwent a
microsurgical clipping of the proximal P2 segment aneurysm and the distal PCA-P2
segment aneurysm was treated by trapping after the application of a superficial
temporal artery (STA) to PCA-P2 bypass using an anterior temporal approach.
RESULTS: Postoperative computed tomography angiography showed the exclusion of
the proximal PCA-P2 aneurysm and an adequate flow from the STA to PCA-P2 bypass
to the distal PCA segments. The patient showed a modified Rankin scale of 0 after
follow-up at 1 and 3 months. CONCLUSIONS: The anterior temporal approach is
feasible for the microsurgical management of complex postcommunicating PCA
aneurysms and the application of bypass procedures.
PMID- 26431732
TI - In Reply to the Letter to the Editor, "Trigeminal Lymphoma and Its Many Faces".
PMID- 26431733
TI - Petrosectomy and Topographical Anatomy in Traditional Kawase and Posterior
Intradural Petrous Apicectomy (PIPA) Approach: An Anatomical Study.
AB - OBJECTIVE: To compare the anatomical exposure and petrosectomy extent in the
Kawase and posterior intradural petrous apicectomy (PIPA) approaches. METHODS:
Kawase and PIPA approaches were performed on 4 fixed cadaveric heads (3 alcohol
fixed, 1 formaldehyde-fixed silicone-injected; 4 Kawase and 4 PIPA approaches).
The microsurgical anatomy was examined by means of Zeiss Opmi CS/NC-4
microscopes. HD Karl Storz Endoscopes (AIDA system) were used to display
intradural exposure. Petrosectomy volumes was assessed by comparing pre- and
postoperative thin-slice computed tomography scans (Analyze 12.0; AnalyzeDirect
Mayo Clinic). RESULTS: The Kawase approach exposed the rhomboid fossa with
Meckel's cave extradurally, the upper half of the clivus, superior
cerebellopontine angle, ventrolateral brainstem, the intrameatal region, basilar
apex, and the preganglionic root of cranial nerve (CN) V, CN III-IV-VI
intradurally. The PIPA approach exposed the cerebello-pontine angle with CN VI
XII, Meckel's cave, CN III-V, and the middle and lower clivus intradurally from a
posterior view. The area of surgical exposure is wide in both approaches;
however, the volume of petrosectomy, the working angle, and surgical corridor
differ significantly. CONCLUSIONS: The Kawase approach allows wide exposure of
the middle cranial fossa (MCF) and posterior cranial fossa, requiring extradural
temporal lobe retraction and an extradural petrosectomy with preservation of the
internal acoustic meatus and cochlea. No temporal lobe retraction and direct
control of neurovascular structures make the PIPA approach a valid alternative
for lesions extending mostly in the Posterior cranial fossa with minor extension
in the MCF. The longer surgical corridor, cerebellar retraction, and limited
exposure of the anterior brainstem make this approach less indicated for lesions
with major extension in the MCF and the anterior cavernous sinus.
PMID- 26431734
TI - Elevated Hemoglobin Concentration Affects Acute Severe Head Trauma After Recovery
from Surgery of Neurologic Function in the Tibetan Plateau.
AB - BACKGROUND: Long-lived inhabitants of the plateau region have a higher hemoglobin
concentration, which is the leading cause of damage in various organs, especially
the nervous system. The aim of this study was to investigate the effect of
hemoglobin concentration on mortality and neural functions after decompressive
craniectomy in patients with hypoxia. METHODS: Patients with acute severe head
trauma were classified into an elevated hemoglobin concentration group (EHb) and
a moderate hemoglobin concentration group (MHb). The survival rate was evaluated
by comparing the Glasgow Coma Score on days 1, 3, 7, and 15 after surgery (Kaplan
Meier survival curve). The Glasgow Outcome Scale classification method was used
to evaluate recovery of neural function. RESULTS: The Glasgow Coma Score scores
on days 3, 7, and 15 were lower in the EHb group compared with the MHb group (P <
0.05). Mortality was significantly higher in the EHb group compared with the MHb
group (P < 0.05). After 6 months, the Glasgow Outcome Scale of the MHb group was
significantly higher than that of the EHb group (P < 0.05). CONCLUSIONS: Elevated
hemoglobin concentration has a serious impact on neurologic recovery and
mortality, as seen in patients with acute severe head trauma after decompressive
craniectomy.
PMID- 26431735
TI - Combination Therapy of Salvianolic Acid and Fluoxetine Improves the Cognitive
Function of Rats with Chronic Stress-induced Depression.
AB - OBJECTIVE: To establish the beneficial effects of salvianolic acid and fluoxetine
on the improvement of cognitive function and amelioration of depression-like
symptoms of rats with chronic stress-induced depression. METHODS: Ninety-nine
male Sprague-Dawley rats were randomly divided into 5 groups--a control group
with no stress challenge and 4 chronic stress groups. Rats assigned to chronic
stress groups were exposed to stress for 3 weeks, and then were given placebo,
fluoxetine (20 mg/kg), salvianolic acid (40 mg/kg), or combined fluoxetine and
salvianolic acid. Body weight of each rat was recorded throughout the study.
Sucrose preference test and water maze experiment were performed after chronic
stress challenge and after drug treatment to assess the effect of drug treatments
on depressive-like symptoms and cognitive function. The sucrose preference test
was also performed before chronic stress exposure for baseline measurement.
RESULTS: Exposure of rats to chronic stress for 3 weeks significantly reduced
body weight and sucrose preference values compared with the no stress control.
The water maze experiment showed that chronic stress impaired the spatial
learning of rats as well. Treatment of stress-challenged rats with fluoxetine and
fluoxetine combined with salvianolic acid resulted in shorter training latency
and longer time spent in the target quadrant during the exploration stage of the
water maze experiment compared with placebo treatment. Effect of the combined
regimen was found more obvious. CONCLUSIONS: Combination therapy of salvianolic
acid and fluoxetine could alleviate depression-like symptoms and cognitive
deficit induced by chronic stress.
PMID- 26431736
TI - Can a Minimal Clinically Important Difference Be Achieved in Elderly Patients
with Adult Spinal Deformity Who Undergo Minimally Invasive Spinal Surgery?
AB - BACKGROUND: Older age has been considered a relative contraindication to complex
spinal procedures. Minimally invasive surgery (MIS) techniques to treat patients
with adult spinal deformity (ASD) have emerged with the potential benefit of
decreased approach-related morbidity. OBJECTIVE: To determine whether a minimal
clinically important difference (MCID) could be achieved in patients ages >= 65
years with ASD who underwent MIS. METHODS: Multicenter database of patients who
underwent MIS for ASD was queried. Outcome metrics assessed were Oswestry
Disability Index (ODI) and visual analog scale (VAS) scores for back and leg
pain. On the basis of published reports, MCID was defined as a positive change of
12.8 ODI, 1.2 VAS back pain, and 1.6 VAS leg pain. RESULTS: Forty-two patients
were identified. Mean age was 70.3 years; 31 (73.8%) were women. Preoperatively,
mean coronal curve, pelvic tilt, pelvic incidence to lumbar lordosis mismatch,
and sagittal vertical axis were 35 degrees , 24.6 degrees , 14.2 degrees , and
4.7 cm, respectively. Postoperatively, mean coronal curve, pelvic tilt, pelvic
incidence to lumbar lordosis, and sagittal vertical axis were 18 degrees , 25.4
degrees , 11.9 degrees , and 4.9 cm, respectively. A mean of 5.0 levels was
treated posteriorly, and a mean of 4.0 interbody fusions was performed. Mean ODI
improved from 47.1 to 25.1. Mean VAS back and leg pain scores improved from 6.8
and 5.9 to 2.7 and 2.7, respectively. Mean follow-up was 32.1 months. For ODI,
64.3% of patients achieved MCID. For VAS back and leg pain, 82.9% and 72.2%,
respectively, reached MCID. CONCLUSIONS: MCID represents the threshold at which
patients feel a meaningful clinical improvement has occurred. Our study results
suggest that the majority of elderly patients with modest ASD can achieve MCID
with MIS.
PMID- 26431737
TI - Theory-of-Mind Training Causes Honest Young Children to Lie.
AB - Theory of mind (ToM) has long been recognized to play a major role in children's
social functioning. However, no direct evidence confirms the causal linkage
between the two. In the current study, we addressed this significant gap by
examining whether ToM causes the emergence of lying, an important social skill.
We showed that after participating in ToM training to learn about mental-state
concepts, 3-year-olds who originally had been unable to lie began to deceive
consistently. This training effect lasted for more than a month. In contrast, 3
year-olds who participated in control training to learn about physical concepts
were significantly less inclined to lie than the ToM-trained children. These
findings provide the first experimental evidence supporting the causal role of
ToM in the development of social competence in early childhood.
PMID- 26431738
TI - Detection of Apoptotic Cells in a Rabbit Model with Atherosclerosis-Like Lesions
Using the Positron Emission Tomography Radiotracer [18F]ML-10.
AB - [18F]ML-10 (2-(5-fluoro-pentyl)-2-methylmalonic acid) is a positron emission
tomography (PET) radiotracer that accumulates in cells presenting apoptosis
specific membrane alterations. The aim of this study was to test whether [18F]ML
10 allows for the detection of apoptotic cells located in atherosclerotic plaques
in rabbits. Atherosclerotic plaques were induced in the aortas of five rabbits,
and five additional rabbits were used as controls. Activity in the aortas was
quantified in vivo and ex vivo. The localization of [18F]ML-10 to the aortic wall
was identified by autoradiography. Average target to background ratios measured
in vivo by PET were higher in the aortas of atherosclerotic rabbits compared with
those of control rabbits (2.00 +/- 0.52 vs 1.22 +/- 0.30; p < .05). Differences
in [18F]ML-10 uptake between atherosclerotic and control aortas were confirmed ex
vivo by PET and gamma counting (23.9 +/- 11.2 vs 1.1 +/- 2.4 counts/pixel; p
<.05; 3.6 +/- 2.0 vs 0.05 +/- 0.05 % of injected activity/g; p < .05,
respectively). Strong correlation was observed between the accumulation of
[18F]ML-10 in aortic segments as detected by autoradiography and the number of
apoptotic cells on corresponding histologic sections (r2 = .75; p < .05). In this
study, we found that atherosclerotic plaques rich in apoptotic cells can be
detected with [18F]ML-10 and PET.
PMID- 26431739
TI - Stage-Specific miRs in Chondrocyte Maturation: Differentiation-Dependent and
Hypertrophy-Related miR Clusters and the miR-181 Family.
AB - Human mesenchymal stromal cells (hMSC) differentiating toward the chondrogenic
lineage recapitulate successive phases of embryonic chondrocyte maturation
developing from progenitor cells to hypertrophic chondrocytes. Osteoarthritic
cartilage is characterized by an alteration in chondrocyte metabolism and
upregulation of hypertrophic differentiation markers. A number of studies point
toward a functional role for microRNAs (miRs) in controlling chondrocyte
differentiation and development of osteoarthritis (OA). However, information on
miRs that may regulate a specific phase of chondrocyte maturation, especially
hypertrophy, is lacking. We here aimed to unravel miR profiles modulated during
chondrogenesis of hMSC to obtain new differentiation markers and potential new
targets relevant for differentiation outcome and OA development. hMSC were
subjected to transforming growth factor-beta (TGF-beta)-driven chondrogenesis and
miR profiles were determined by microarray analysis at distinct developmental
time points. Expression of selected miRs was compared to cultures lacking
chondrogenesis and to redifferentiated nonhypertrophic articular chondrocytes.
Among 1349 probed miRs, 553 were expressed and 169 (31%) were significantly
regulated during chondrogenesis. Hierarchical clustering identified specific miR
expression patterns representative for MSC, prechondrocytes, chondroblasts,
chondrocytes, and hypertrophic chondrocytes, respectively. Regulation of miR-181
family members allowed discrimination of successive differentiation stages.
Levels of several miRs, including miR-23b, miR-140, miR-181, and miR-210
positively correlated with successful chondrocyte formation. Hypertrophic MSC
derived chondrocytes and nonhypertrophic articular chondrocytes showed
differential expression of miR-181a, miR-210, and miR-31, but not miR-148a
implicated in COL10A1-regulation. We conclude that the here identified stage
dependent miR clusters may have imperative functions during chondrocyte
differentiation providing novel diagnostic tools and targets of potential
relevance for OA development.
PMID- 26431740
TI - Impact of perinatal mental health education on student midwives' knowledge,
skills and attitudes: A pre/post evaluation of a module of study.
AB - BACKGROUND: Whilst midwives are well-placed to identify and address the mental
health need of women in their care, many report lacking the ability to do so.
Therefore, they ignore or brush aside women's mental health needs. To improve
midwives' competency in this area, the first authors developed and delivered a
module on perinatal mental health issues within their university. The module
aimed to improve knowledge, skills, and attitudes in relation to working with
women about mental health issues. In 2012, a post-survey evaluation of the module
demonstrated positive findings; following a number of revisions to the module,
this more robust pre/post evaluation was conducted. OBJECTIVES: The objective of
this study was to examine the impact of the perinatal mental health module on
student midwives' knowledge, skills, and attitudes in addressing mental health
issues with women. Design Pre-module and Post-module Surveys were Used.
PARTICIPANTS: Participants were students undertaking a 4-year undergraduate
direct entry midwifery degree programme in Ireland. The pre-survey had 28
participants, the post-survey had 26 participants, and there were 25 matched
pairs. METHODS: The data were analysed using SPSS Version 21.0. Descriptive,
frequencies and paired sample t-tests were calculated. Qualitative data were
analysed thematically. RESULTS: Comparison of the pre and post measures, based on
paired samples t-tests, showed that the programme statistically increased
participants' knowledge and skills. Whilst students' self-reported attitudes
towards women and mental health issues were already quite positive, they reported
even more positive attitudes following the course. Written feedback provided by
students also supported these positive findings. CONCLUSION: This evaluation
provides evidence that a module on perinatal mental health is effective at
improving the self-reported knowledge, skills, and attitudes of student midwives
towards women with mental health issues. It is recommended that educators
consider the opportunity of including a similar module in their curriculum.
PMID- 26431742
TI - "It's a Burden You Carry": Describing Moral Distress in Emergency Nursing.
AB - INTRODUCTION: Moral distress in nursing has been studied in many settings, but
there is a paucity of research on moral distress as it manifests in the emergency
department. One study suggests a correlation between moral distress and aspects
of burnout, and other researchers report that nurses have considered leaving
their position or even their profession because of moral distress. Further
exploration of these issues may provide insight into their effects on ED patient
care and the emergency nursing profession. The purpose of this study was to
explore the nature of moral distress as it is experienced and described by
emergency nurses. METHODS: A qualitative, exploratory design was employed using
semi-structured focus groups for data collection. Using an iterative process,
transcripts were analyzed for emerging themes by the research team. Six
researchers analyzed the transcripts using a thematic analysis approach. RESULTS:
Themes from the data included dysfunctional practice arena, being overwhelmed,
and adaptive/maladaptive coping. Participants described, overall, a profound
feeling of not being able to provide patient care as they wanted to. DISCUSSION:
Causes of moral distress in emergency nurses are environment driven, not incident
driven, as is described in other settings, and include a high-acuity, high
demand, technical environment with insufficient resources. Interventions should
be targeted to improve environmental factors that contribute to the moral
distress of emergency nurses. Future research should focus on the development and
validation of an instrument to measure moral distress in this setting.
PMID- 26431743
TI - Spectral entropy in monitoring anesthetic depth.
AB - Monitoring the brain response to hypnotics in general anesthesia, with the
nociceptive and hemodynamic stimulus interaction, has been a subject of intense
investigation for many years. Nowadays, monitors of depth of anesthesia are based
in processed electroencephalogram by different algorithms, some of them unknown,
to obtain a simplified numeric parameter approximate to brain activity state in
each moment. In this review we evaluate if spectral entropy suitably reflects the
brain electric behavior in response to hypnotics and the different intensity
nociceptive stimulus effect during a surgical procedure.
PMID- 26431741
TI - Overexpression of the monocyte chemokine CCL2 in dorsal root ganglion neurons
causes a conditioning-like increase in neurite outgrowth and does so via a STAT3
dependent mechanism.
AB - Neuroinflammation plays a critical role in the regeneration of peripheral nerves
following axotomy. An injury to the sciatic nerve leads to significant macrophage
accumulation in the L5 DRG, an effect not seen when the dorsal root is injured.
We recently demonstrated that this accumulation around axotomized cell bodies is
necessary for a peripheral conditioning lesion response to occur. Here we asked
whether overexpression of the monocyte chemokine CCL2 specifically in DRG neurons
of uninjured mice is sufficient to cause macrophage accumulation and to enhance
regeneration or whether other injury-derived signals are required. AAV5-EF1alpha
CCL2 was injected intrathecally, and this injection led to a time-dependent
increase in CCL2 mRNA expression and macrophage accumulation in L5 DRG, with a
maximal response at 3 weeks post-injection. These changes led to a conditioning
like increase in neurite outgrowth in DRG explant and dissociated cell cultures.
This increase in regeneration was dependent upon CCL2 acting through its primary
receptor CCR2. When CCL2 was overexpressed in CCR2-/- mice, macrophage
accumulation and enhanced regeneration were not observed. To address the
mechanism by which CCL2 overexpression enhances regeneration, we tested for
elevated expression of regeneration-associated genes in these animals.
Surprisingly, we found that CCL2 overexpression led to a selective increase in
LIF mRNA and neuronal phosphorylated STAT3 (pSTAT3) in L5 DRGs, with no change in
expression seen in other RAGs such as GAP-43. Blockade of STAT3 phosphorylation
by each of two different inhibitors prevented the increase in neurite outgrowth.
Thus, CCL2 overexpression is sufficient to induce macrophage accumulation in
uninjured L5 DRGs and increase the regenerative capacity of DRG neurons via a
STAT3-dependent mechanism.
PMID- 26431744
TI - The use of pupillometry as monitoring of intraoperative analgesia in the
consumption of analgesics during the first 12 hours after surgery.
AB - INTRODUCTION: Intraoperative evaluation of analgesia remains today often based on
heart rate and arterial pressure fluctuations. None of these parameters is
specific. Incorrect handling during this process may increase surgical morbi
mortality of the patients and their acute postoperative pain. The aim of this
study was to evaluate the impact of intraoperative analgesia controlled by
pupillometry on postoperative analgesic consumption and the pain intensity in the
first 12h in the hospital room, after major gynecological surgery. PATIENTS AND
METHODS: A prospective, cohort study with allocation of groups of sequentially
according to programming of operating room was designed. ASA I-III patients
scheduled for elective surgery of abdominal hysterectomy by laparotomy or
laparoscopy through intravenous general anesthesia were included. Patients were
divided into 2 groups: pupillometry group (P-1), in which intraoperative
analgesia was guided by pupillometry, and hemodynamic group (H-2) according to
values of blood pressure and heart rate. In the hospitalization room the values
of visual analogue scale (VAS) were routinely registered with 3 courts for the
study: 3, 8 and 12h of the postoperative period. Postoperative analgesia was
standardized as follows: NSAIDs was administered if VAS was >= 3 or if the
patient expressly requested an analgesic. After this, the efficacy of treatment
was assessed. If the patient had pain, the next scheduled drug was given up to an
VAS<3. Data for total analgesic consumption administered in the hospital room,
VAS and adverse effects were collected within 12h postoperatively. RESULTS: A
total of 59 patients, 30 group P-1 and 29 group H-2, were included. Group P-1
experienced less pain than group H-2, with statistical significance in each phase
(VAS 3h, VAS 8h and VAS 12h). These data are consistent with the consumption of
analgesics for patients. There was a statistically significant reduction
(p<0.001) in the group P-1 (1.80 [DE 0.99]; medium 2, 95% confidence interval
1.43-2.17) compared with group H-2 (5.66 [1.58]; medium 6, 95% confidence
interval 5.05-6.26). CONCLUSIONS: Monitoring of the intraoperative analgesia by
pupillometry was able to reduce the intensity of the acute postoperative pain and
analgesic consumption in the first 12h in the hospital room after major
gynecological surgery.
PMID- 26431745
TI - [Use of MRI before biopsy in diagnosis of prostate cancer: Single-operator
study].
AB - The diagnostic for prostate cancer is changing. To improve the detection of this
cancer, urologists expect a lot from the contribution of magnetic resonance
imaging (MRI). What is the role of this imaging in prostate cancer detection?
This is a retrospective study, from 2011 to 2013, mono-centric and single
operator. Of the 464 needle biopsy of the prostate (BP), we excluded those with
PSA>20 ng/mL or digital rectal examination (DRE)>T3. The remaining 430 BP were
submitted or not to a 1.5 tesla MRI with pelvic antenna. The primary aim is the
overall detection of prostate cancer. Secondary aim was the detection rate during
the first series of BP and repeat BP, between the two groups in the MRI group.
MRI and MRI without populations are comparable for age (63.3 vs 64.6), PSA (6.10
vs 6.13), DRE>T1c, prostate volume (55.4 cm(3) vs 51.7 cm(3)). There is no
significant difference in overall detection between the two groups (P=0.12).
There is no significant difference in cancer detection between the first BP
(P=0.13) and the repeat BP (P=0.07). There is a significant difference in the
early detection of BP MRI group (P=0.03) but not for the BP repeat MRI group
(P=0.07). For 108 BP iterative MRI group, there were 67 BP targeted "mentally"
with MRI: 18 cancers were detected, making a 25% detection rate. This study helps
to highlight the value of MRI in the early rounds of BP but we can ask the value
of this imaging during repeat biopsies. Targeted biopsies "mentally" do not have
the expected detection sensitivity and seems to require a three-dimensional
reconstruction to be more effective. LEVEL OF EVIDENCE: 5.
PMID- 26431746
TI - What risk of prostate cancer led urologist to recommend prostate biopsies?
AB - OBJECTIVE: The aim of this study was to estimate the risk of prostate cancer that
led urologists to perform prostate biopsies. PATIENTS AND METHODS: Eight hundred
and eight patients had prostate biopsies in 5 tertiary centres in 2010. Following
data were collected: age, PSA, DRE, prostate volume, negative prior prostate
biopsy and estimated life expectancy (> or <10 years). The risk of prostate
cancer was calculated by validated nomogram of PCPT-CRC and SWOP-PRI and
correlated with pathological biopsy results. RESULTS: In final analysis, 625
patients were included, 568 (90.9%) had a life expectancy greater than 10 years.
Prostate cancer was found in 291 (46.6%) cases. These patients were older (66.7
+/- 6.8 vs 64.3 +/- 5.6 years, P < 0.001), had higher PSA values (10 +/- 7.9 vs
7.7 +/- 4.3 ng/mL, P < 0.0001) and the prostate volume decreased (43.8 +/- 19.8
vs 51.3 +/- 20.7 mL, P < 0.0001) compared with healthy subjects. Digital Rectal
Examination was more frequently suspicious in the group of patients with prostate
cancer (43.6% vs 18.9%, P < 0.0001). Risk of prostate cancer estimated was 50.6
+/- 14% for PCPT-CRC without ATCD, 56.2 +/- 12.8% with PCPT-CRC ATCD and 31.2 +/-
17.3% for SWOP-PRI. The likelihood of high-risk prostate cancer was 22.4 +/-
16.9% with the PCPT-CRC, and 14.8 +/- 18.2% with SWOP-PRI. CONCLUSION: This study
showed that urologists performed prostate biopsies when the risk of cancer was
high.
PMID- 26431747
TI - Where do we stand? Functional imaging in acute and chronic pulmonary embolism
with state-of-the-art CT.
AB - Nowadays, CT pulmonary angiography (CTPA) is the diagnostic imaging modality of
choice for acute and chronic pulmonary embolism (PE) in order to assess vascular
anatomy and parenchymal morphology. Over the past decade, several prognostic CTPA
markers associated with an increased risk of adverse clinical events and in
hospital mortality have been evaluated, namely cardiac chamber dimensions,
obstruction scores, and visualization of iodinated contrast material in the lung
parenchyma by dual-energy (DE) CTPA. This article reviews the current status and
potential prognostic advantages of CTPA or DE CTPA with its recent developments
for accessing right ventricular dysfunction and the assessment of first pass lung
perfusion with DE CTPA in the diagnosis of acute and chronic PE.
PMID- 26431748
TI - The radiological assessment of colonic replacement of the esophagus in children:
A review of 43 cases.
AB - PURPOSE: To define the characteristic radiological features following colonic
replacement of the esophagus in children. MATERIALS AND METHODS: The upper gastro
intestinal contrast studies of 43 patients who underwent colonic replacement of
the esophagus at our pediatric surgery unit were available for analysis. UGI
contrast studies were performed routinely in the post-surgical period in 17 cases
(first asymptomatic group), while the rest of contrast studies (26) belonged to a
second group of out-patients complaining of dysphagia (18) or dyspepsia (8)
following colonic replacement of the esophagus. Based on our observations, we
proposed a grading system to describe the degree of colonic redundancy in the
thorax. RESULTS: Redundancy of the colonic conduit in the thoracic cavity was a
common radiological finding (62.8%). The redundancy was mild (grade 1) in 18
patients, moderate (grade 2) in eight, and severe (grade 3) in only one patient.
In 88.9%, the redundancy was in the right hemi-thorax. Patients presenting with
postoperative dysphagia had a stricture at the site of the esophago-colic
anastomosis in the neck, which should be differentiated from other sites of
anatomical narrowing at the inlet and outlet of the thoracic cavity. Gastro-colic
reflux was common among patients who underwent colonic replacement of the
esophagus without an anti-reflux procedure. CONCLUSION: Colonic replacement of
the esophagus in children results in considerable anatomical alterations.
Knowledge about the normal post-surgical changes and imaging features of the
commonly encountered complications can increase the diagnostic confidence among
radiologists and clinicians when dealing with these cases.
PMID- 26431749
TI - Pseudoaneurysm of the Perforating Peroneal Artery After Ankle Fracture Fixation:
Case Report and Review of the Literature.
AB - Pseudoaneurysm formation around the ankle area is a very rare complication of an
anatomic region that is highly exposed to trauma. A review of the published
medical data revealed the rarity of the condition. Pseudoaneurysms of the
perforating branch of the peroneal artery account for only 8 in the published
data, with 6 (75%) cases related to sprain injury and only 2 (25%) to fracture
fixation. We present a pseudoaneurysm of the perforating peroneal artery after a
bimalleolar ankle fracture in a patient taking warfarin and a review of the
published data. Our patient was treated successfully with thrombin embolization,
and at 6 weeks after embolization, she remained completely free of symptoms.
PMID- 26431750
TI - Guided Growth With Temporary Hemiepiphysiodesis to Treat Ankle Valgus in a
Skeletally Immature Individual: A Case Report.
AB - Guided growth is useful in correcting pediatric angular deformities. Ankle valgus
is a coronal plane deformity and is often seen in skeletally immature patients
with congenital or acquired lower extremity pathologic features. Temporary
hemiepiphysiodesis with a percutaneous transphyseal medial malleolar screw is a
surgical treatment capable of correcting the angular deformity and can offer
effective correction. In the present case study, a 12-year-old male with dorsal
lateral peritalar subluxation and ankle valgus underwent a reconstructive
procedure and temporary hemiepiphysiodesis with a percutaneous medial malleolar
screw. After removal of the screw, reduction of his peritalar subluxation was
achieved, improving his lateral-distal tibial angle from 81 degrees
preoperatively to 89 degrees at the final follow-up examination. The patient
returned to his preoperative sporting activities and ambulated comfortably and
pain free in sneakers with orthotics. In conclusion, temporary hemiepiphysiodesis
with a transphyseal medial malleolar screw is an effective treatment option for
ankle valgus in a skeletally immature individual.
PMID- 26431751
TI - Integration of moral values during L2 sentence processing.
AB - This study reports an event-related potential (ERP) experiment examining whether
valuation (i.e., one's own values) is integrated incrementally and whether it
affects L2 speakers' online interpretation of the sentence. We presented Spanish
native speakers and French-Spanish mid-proficiency late L2 speakers with visual
sentences containing value-consistent and value-inconsistent statements (e.g.,
'Nowadays, paedophilia should be prohibited/tolerated across the world.').
Participants' brain activity was recorded as they were reading the sentences and
indicating whether they agreed with the statements or not. Behaviourally, the two
groups revealed identical valuation. The ERP analyses showed both a semantic
(N400) and an affect-related response (LPP) to value-inconsistent statements in
the native group, but only an LPP in the non-native group. These results suggest
that valuation is integrated online (presence of LPP) during L2 sentence
comprehension but that it does not interfere with semantic processing (absence of
N400).
PMID- 26431752
TI - Biomechanical response to ladder slipping events: Effects of hand placement.
AB - Ladder falling accidents are a significant, growing and severe occupational
hazard. The factors that contribute to falls from ladders and specifically those
that influence the motor response from ladder falls are not well understood. The
aims of this research were to determine the effects of hand placement (rung
versus rail) on muscle activation onset and peak activity timing in response to
slipping on a ladder and to sequence the timing of events following slip
initiation. Fifteen unexpected slips from 11 experienced ladder climbers were
induced with a freely spinning rung under the foot, while subjects were randomly
assigned to a rung versus rail hand grasping strategy. EMG onset time and peak
activity time from five bilateral muscles (semitendinosis, vastus lateralis,
triceps, biceps and anterior deltoid) were analyzed. Results indicated that
significantly slower muscle activation onset and peak response times occurred
during rail hand placement, suggesting that grasping ladder rungs may be
preferable for improving the speed of the motor response. The triceps muscle
activated and reached peak activity earlier in the slip indicating that subjects
may initially extend their arms prior to generating hand forces. The study also
revealed that slips tended to occur around the time that a foot and hand were in
motion and there were just two points of contact (one hand and the slipping
foot).
PMID- 26431753
TI - Compensatory mechanisms of balance to the scaling of arm-swing frequency.
AB - The present study investigated the contribution of the Hof (2007) mechanism 1 (M1
moving the center of pressure (COP) with respect to the vertical projection of
the center of mass (COMTotal)); and mechanism 2 (M2-rotating the trunk and upper
limbs around the COMTotal) to postural control and the stability of COP-COMTotal
cophase as a function of lateral arm-swing frequency. Young adults were
instructed to stand still on a force platform while alternating their arm
swinging from above the head to the side of their thigh to create perturbations
to postural control. Scaling the frequency of arm-swing (random step changes of
0.2 Hz within a bandwidth of 0.2 to 1.6 Hz) increased the SD of COP but decreased
the SD of COMTotal. Increments in arm-swing frequency induced a progressive
increase in M1 and decrease in M2 in terms of their relative contribution to
postural stability. The cophase between COP and COMTotal became more tightly in
phase over increments of arm-swing frequency. These findings show an adaptive
compensatory role of M1 and M2 within the stability of COP-COMTotal coupling in
the regulation of human balance control.
PMID- 26431754
TI - Wear simulation of total knee prostheses using load and kinematics waveforms from
stair climbing.
AB - Knee wear simulators are meant to perform load cycles on knee implants under
physiological conditions, matching exactly, if possible, those experienced at the
replaced joint during daily living activities. Unfortunately, only conditions of
low demanding level walking, specified in ISO-14243, are used conventionally
during such tests. A recent study has provided a consistent knee kinematic and
load data-set measured during stair climbing in patients implanted with a
specific modern total knee prosthesis design. In the present study, wear
simulation tests were performed for the first time using this data-set on the
same prosthesis design. It was hypothesised that more demanding tasks would
result in wear rates that differ from those observed in retrievals. Four
prostheses for total knee arthroplasty were tested using a displacement
controlled knee wear simulator for two million cycles at 1.1 Hz, under kinematics
and load conditions typical of stair climbing. After simulation, the
corresponding damage scars on the bearings were qualified and compared with
equivalent explanted prostheses. An average mass loss of 20.2+/-1.5 mg was found.
Scanning digital microscopy revealed similar features, though the explant had a
greater variety of damage modes, including a high prevalence of adhesive wear
damage and burnishing in the overall articulating surface. This study confirmed
that the results from wear simulation machines are strongly affected by
kinematics and loads applied during simulations. Based on the present results for
the full understanding of the current clinical failure of knee implants, a more
comprehensive series of conditions are necessary for equivalent simulations in
vitro.
PMID- 26431756
TI - Reducing health disparities: the role of sleep deficiency and sleep disorders.
AB - Decrements in sleep health, including insufficient sleep duration, irregular
timing of sleep, poor sleep quality, and sleep/circadian disorders, are
widespread in modern society and are associated with an array of disease risks
and outcomes, including those contributing to health disparities (eg,
cardiovascular disease, obesity and diabetes, psychiatric illness, and cancer).
Recent findings have uncovered racial/ethnic and socioeconomic position
differences in sleep health; however, the contribution of sleep deficiency to
health disparities remains largely unexplored, and understanding the underlying
causes of disparities in sleep health is only beginning to emerge. In 2011, the
National Heart, Lung, and Blood Institute (NHLBI) convened a workshop, bringing
together sleep and health disparities investigators, to identify research gaps
and opportunities to advance sleep and health disparities science. This article
provides a brief background and rationale for the workshop, and it disseminates
the research recommendations and priorities resulting from the working group
discussions.
PMID- 26431757
TI - Cross-sectional sleep thresholds for optimal health and well-being in Australian
4-9-year-olds.
AB - AIM: Using national Australian time-diary data, we aimed to empirically determine
sleep duration thresholds beyond which children have poorer health, learning,
quality of life, and weight status and parents have poorer mental health.
METHODS: DESIGN/SETTING: Cross-sectional data from the first three waves of the
Longitudinal Study of Australian Children. PARTICIPANTS: A nationally
representative sample of 4983 4-5-year-olds, recruited in 2004 from the
Australian Medicare database and followed biennially; 3631 had analyzable sleep
information and a concurrent measure of health and well-being for at least one
wave. MAIN MEASURES: EXPOSURE: At each wave, a parent completed 24-h time-use
diaries for one randomly selected weekday and one weekend day, including a
"sleeping/napping" category. OUTCOMES: Parent-reported child mental health,
health-related quality of life, and maternal/paternal mental health; teacher
reported child language, literacy, mathematical thinking, and approach to
learning; and assessed child body mass index and girth. RESULTS: Linear
regression analyses revealed weak, inconsistent relationships between sleep
duration and outcomes at every wave. For example, children with versus without
psychosocial health-related quality of life problems slept slightly less at 6-7
years (adjusted mean difference 0.12 h; 95% confidence interval 0.01-0.22, p =
0.03), but not at 4-5 (0.00; -0.10 to 0.11, p = 1.0) or 8-9 years (0.09; -0.02 to
0.22, p = 0.1). Empirical exploration using fractional polynomials demonstrated
no clear thresholds for sleep duration and any adverse outcome at any wave.
CONCLUSIONS: Present guidelines in terms of children's short sleep duration
appear misguided. Other parameters such as sleep timing may be more meaningful
for understanding optimal child sleep.
PMID- 26431755
TI - Sleep disparity, race/ethnicity, and socioeconomic position.
AB - Sleep represents a set of biological functions necessary for the maintenance of
life. Performing these functions, though, requires that an individual engage in
behaviors, which are affected by social and environmental factors. Race/ethnicity
and socioeconomic position represent categories of factors that likely play a
role in the experience of sleep in the community. Previous studies have suggested
that racial/ethnic minorities and the socioeconomically disadvantaged may be more
likely to experience sleep patterns that are associated with adverse health
outcomes. It is possible that disparities in sleep represent a pathway by which
larger disparities in health emerge. This review (1) contextualizes the concept
of race/ethnicity in biomedical research, (2) summarizes previous studies that
describe patterns of sleep attainment across race/ethnicity groups, (3) discusses
several pathways by which race/ethnicity may be associated with sleep, (4)
introduces the potential role of socioeconomic position in the patterning of
sleep, and (5) proposes future research directions to address this issue.
PMID- 26431759
TI - Medical Expulsive Therapy for Ureteric Colic: New Hard Evidence: Commentary on:
Medical expulsive therapy in adults with ureteric colic: a multicentre,
randomised, placebo-controlled trial.
PMID- 26431760
TI - Editorial Comment.
PMID- 26431761
TI - Reply: To PMID 26276574.
PMID- 26431762
TI - Current State of Urologic Malpractice in Spain.
PMID- 26431758
TI - Association between sleep deficiency and cardiometabolic disease: implications
for health disparities.
AB - BACKGROUND: Cardiometabolic diseases, which include obesity, diabetes,
hypertension, and cardiovascular disease, are associated with reduced quality of
life and reduced life expectancy. Unfortunately, there are racial/ethnic and
socioeconomic disparities associated with these diseases such that minority
populations, such as African Americans and Hispanics, and those of lower
socioeconomic status, experience a greater burden. Several reports have indicated
that there are differences in sleep duration and quality that mirror the
disparities in cardiometabolic disease. The goal of this paper is to review the
association between sleep and cardiometabolic disease risk because of the
possibility that suboptimal sleep may partially mediate the cardiometabolic
disease disparities. METHODS: We review both experimental studies that have
restricted sleep duration or impaired sleep quality and examined biomarkers of
cardiometabolic disease risk, including glucose metabolism and insulin
sensitivity, appetite regulation and food intake, and immune function. We also
review observational studies that have examined the association between habitual
sleep duration and quality, and the prevalence or risk of obesity, diabetes,
hypertension, and cardiovascular disease. CONCLUSION: Many experimental and
observational studies do support an association between suboptimal sleep and
increased cardiometabolic disease risk.
PMID- 26431763
TI - Behavior and the cholinergic parameters in olfactory bulbectomized female
rodents: Difference between rats and mice.
AB - Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional
disturbances, including behavioral, neurochemical, and neuromorphological
alterations. We have examined the effects of OBX on behavior and the parameters
of the cholinergic system in female rats and mice. In rats, OBX resulted in the
appearance of some depressive-like behavioral marks, such as the decreased
sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like
behavioral features, such as shortened presence in the center of the open field
arena or open arms of the elevated plus-maze and an enhancement of avoidance
behavior. These behavioral abnormalities could be associated with disturbances in
hippocampal function, this suggestion being supported by the presence of cellular
changes in this brain structure. No effect of OBX on the number of cholinergic
neurons in the medial septum-diagonal band as well as on the acetylcholine
content and acetylcholinesterase activity in the septum, hippocampus, and
neocortex could be detected. In contrast, in mice, OBX impaired spontaneous
alternation behavior and decreased the number of cholinergic neurons in the
medial septum-diagonal band. These data demonstrate that rats and mice
differently respond to OBX, in particular, OBX does not significantly affect the
cholinergic system in rats.
PMID- 26431764
TI - A prolonged motor imagery session alter imagined and actual movement durations:
Potential implications for neurorehabilitation.
AB - Mental practice with motor imagery improves motor performance, for example
reducing the duration of goal-directed movements. However, it is not known
whether an experimental session involving prolonged sequences of motor imagery
induces mental fatigue and alters motor and mental performances. In this study,
participants imagined 100 point-to-point arm movements combined with actual
pointing movements every 10 or 50 imagined movements. Participants reported a
subjective feeling of mental fatigue after imagining 100 pointing movements. When
participants performed actual movements every 50 imagined movements, the duration
of both actual and imagined movements increased at the end of the protocol. On
the contrary, no change in actual and imagined movement duration was observed
when participants performed actual movements every 10 imagined movements. These
results suggested that the repetition of many imagined movements induced mental
fatigue and altered the mental simulation and the actual execution processes of
the movement. However, the regular execution of actual movements seemed to
counteract the negative effect of mental fatigue as both actual and imagined
movement duration remained constant with actual trials inserted between mental
rehearsals. We suggest that during training or rehabilitation programs, actual
movements should be executed and/or imagined movement duration should be
controlled to avoid the negative effects of mental fatigue on motor performance.
PMID- 26431765
TI - Modulation of prism adaptation by a shift of background in the monkey.
AB - Recent human behavioral studies have shown that the position of a visual target
is instantly represented relative to the background (e.g., a large square) and
used for evaluating the error in reaching the target. In the present study, we
examined whether the same allocentric mechanism is shared by the monkey. We
trained two monkeys to perform a fast and accurate reaching movement toward a
visual target with a square in the background. Then, a visual shift (20mm or 4.1
degrees ) was introduced by wedge prisms to examine the process of decreasing the
error during an exposure period (30 trials) and the size of the error upon
removal of the prisms (aftereffect). The square was shifted during each movement,
either in the direction of the visual displacement or in the opposite direction,
by an amount equal to the size of the visual shift. The ipsilateral shift of the
background increased the asymptote during the exposure period and decreased the
aftereffect, i.e., prism adaptation was attenuated by the ipsilateral shift. By
contrast, a contralateral shift enhanced adaptation. We further tested whether
the shift of the square alone could cause an increase in the motor error.
Although the target did not move, the shift of the square increased the motor
error in the direction of the shift. These results were generally consistent with
the results reported in human subjects, suggesting that the monkey and the human
share the same neural mechanisms for representing a target relative to the
background.
PMID- 26431766
TI - Olfactory bulbectomy increases reinstatement of methamphetamine seeking after a
forced abstinence in rats.
AB - Drug addiction is commonly associated with depression and comorbid patients also
suffer from higher cravings and increased relapse rate. To address this issue
preclinically we combined the olfactory bulbectomy (OBX) model of depression and
intravenous methamphetamine self-administration procedure in rats to assess
differences in relapse-like behavior. Male Sprague-Dawley rats were divided
randomly into two groups; in one group the bilateral olfactory bulbectomy (OBX)
was performed while the other group was sham operated. After recovery,
intracardiac catheter was implanted. Intravenous self-administration procedure
was conducted in operant boxes using nose-poke operandi (Coulbourn Instruments,
Inc., USA) under fixed ratio 1 schedule of reinforcement. Methamphetamine was
available at dose 0.08 mg/kg/infusion. After stable methamphetamine intake was
maintained, a period of forced abstinence was initiated and rats were kept in
their home-cages for 14 days. Finally, one reinstatement session was conducted in
operant boxes with no drug delivery. In the reinstatement session the mean of
138.4 active nose-pokes was performed by the OBX group, while the sham group
displayed 41 responses, i.e. 140 % and 48 % of basal nose-poking during
maintenance phase in OBX and sham operated group respectively. OBX group also
showed significantly more passive nose-pokes indicating hyperactive behavioral
traits in bulbectomized rats. However, the % of active operandum preference was
equal in both groups. Olfactory bulbectomy model significantly increased
reinstatement of methamphetamine seeking behavior. This paradigm can be used to
evaluate potential drugs that are able to suppress the drug-seeking behavior.
PMID- 26431767
TI - Evaluation of the short- and long-term safety and therapy outcomes of the
everolimus-eluting bioresorbable vascular scaffold system in patients with
coronary artery stenosis: Rationale and design of the German-Austrian ABSORB
RegIstRy (GABI-R).
AB - BACKGROUND: Third-generation drug-eluting metal stents are the gold standard for
treatment of coronary artery disease. The permanent metallic caging of the
vessel, however, can result in limited vasomotion, chronic inflammation, and late
expansive remodeling, conditions that can lead to late and very late stent
thrombosis. The development of bioresorbable scaffolds (BRSs) promises advantages
over metal stents due to complete biodegradation within 2-4years. Theoretically,
since vessel scaffolding is temporary and no permanent implant remains in the
vessel, BRSs, as opposed to metal stents, once degraded would no longer be
potential triggers for stent-related adverse events or side effects.
METHODS/DESIGN: The short- and long-term outcome after implantation of an
everolimus-eluting, poly-L-lactic acid-based bioresorbable scaffold system
(ABSORB, Abbott Vascular, Santa Clara, CA, USA) in the world-wide greatest all
comers cohort will be evaluated in the prospective, non-interventional,
multicenter German-Austrian ABSORB RegIstRy (GABI-R). GABI-R will include over
5000 patients from about 100 study sites in Austria and Germany. Safety endpoints
such as cardiac death, myocardial infarction, and clinically driven percutaneous
or surgical target lesion and vessel revascularization will be evaluated during
hospitalization and in the follow-up period (minimum of 5years). CONCLUSION:
Although two randomized controlled trials and several registries have documented
safety and efficacy as well as non-inferiority of this everolimus-eluting ABSORB
device compared with drug-eluting metal stents, the current knowledge regarding
clinical application, treatment success, and long-term safety of using this BRS
in daily routine is limited. Thus, the goal of GABI-R is to address this lack of
information.
PMID- 26431768
TI - Reliability of measures of transient evoked otoacoustic emissions with
contralateral suppression.
AB - The reliability of measures of transient evoked otoacoustic emissions (TEOAEs)
with contralateral suppression was examined. The effect of test session (i.e.,
initial test; retest without probe removal; retest with probe removal; and retest
1-2 days post initial test), gender, and ear was examined in 14 young adult
females and 14 young adult males. TEOAEs were obtained bilaterally with 60 dB
peSPL linear click stimuli with and without a contralateral 65 dB SPL broadband
noise suppressor. Absolute TEOAE suppression and a normalized index of TEOAE
suppression (i.e., percentage of suppression) were examined. Reliability of these
measures was assessed with repeated measures linear mixed model analysis of
variance, a coefficient of reliability, and Bland-Altman analyses. There were no
statistically significant (p>0.05) main effects of test, gender, and ear or
interactions for both absolute dB and % TEOAE suppression values. Cronbach's
alpha were greater than 0.90 across the four tests for both TEOAE measures. Mean
test differences or bias (i.e., between the initial and subsequent tests) for
absolute and % TEOAE suppression ranged from -0.05 to 0.11 dB and -1.5% to 1.1%,
respectively. There was no proportional/systematic bias with the mean differences
of the first and subsequent measurements. Data herein were consistent with the
view that bilateral TEOAE suppression measures are reliable across test sessions
of 1-2 days among females and males and may provide a method to monitor medial
olivocochlear efferent reflex status over time.
PMID- 26431769
TI - Sit-and-wait versus active-search hunting: A behavioral ecological model of
optimal search mode.
AB - Drawing on Skellam's (1958) work on sampling animal populations using transects,
we derive a behavioral ecological model of the choice between sit-and-wait and
active-search hunting. Using simple, biologically based assumptions about the
characteristics of predator and prey, we show how an empirically definable
parameter space favoring active-search hunting expands as: (1) the average rate
of movement of prey decreases, or (2) the energetic costs of hunter locomotion
decline. The same parameter space narrows as: (3) prey skittishness increases as
a function of a hunter's velocity, or (4) prey become less detectable as a
function of a hunter's velocity. Under either search tactic, encounter rate
increases as a function of increasing prey velocity and increasing detection zone
radius. Additionally, we investigate the roles of habitat heterogeneity and
spatial auto-correlation or grouping of prey on the optimal search mode of a
hunter, finding that habitat heterogeneity has the potential to complicate
application of the model to some empirical examples, while the effects of prey
grouping lead to relatively similar model outcomes. As predicted by the model,
the introduction of the horse to the Great Plains and the introduction of the
snowmobile to Arctic foraging communities decreased the metabolic costs of active
search and led to a change in normative hunting strategies that favored active
search in place of sit-and-wait hunting.
PMID- 26431770
TI - Additive genetic variation and evolvability of a multivariate trait can be
increased by epistatic gene action.
AB - Epistatic gene action occurs when mutations or alleles interact to produce a
phenotype. Theoretically and empirically it is of interest to know whether gene
interactions can facilitate the evolution of diversity. In this paper, we explore
how epistatic gene action affects the additive genetic component or heritable
component of multivariate trait variation, as well as how epistatic gene action
affects the evolvability of multivariate traits. The analysis involves a sexually
reproducing and recombining population. Our results indicate that under
stabilizing selection conditions a population with a mixed additive and epistatic
genetic architecture can have greater multivariate additive genetic variation and
evolvability than a population with a purely additive genetic architecture. That
greater multivariate additive genetic variation can occur with epistasis is in
contrast to previous theory that indicated univariate additive genetic variation
is decreased with epistasis under stabilizing selection conditions. In a
multivariate setting, epistasis leads to less relative covariance among
individuals in their genotypic, as well as their breeding values, which
facilitates the maintenance of additive genetic variation and increases a
population's evolvability. Our analysis involves linking the combinatorial nature
of epistatic genetic effects to the ancestral graph structure of a population to
provide insight into the consequences of epistasis on multivariate trait
variation and evolution.
PMID- 26431771
TI - Noise-plasticity correlations of gene expression in the multicellular organism
Arabidopsis thaliana.
AB - Gene expression levels exhibit stochastic variations among genetically identical
organisms under the same environmental conditions (called gene expression "noise"
or phenotype "fluctuation"). In yeast and Escherichia coli, positive correlations
have been found between such gene expression noise and "plasticity" with
environmental variations. To determine the universality of such correlations in
both unicellular and multicellular organisms, we focused on the relationships
between gene expression "noise" and "plasticity" in Arabidopsis thaliana, a
multicellular model organism. In recent studies on yeast and E. coli, only some
gene groups with specific properties of promoter architecture, average expression
levels, and functions exhibited strong noise-plasticity correlations. However, we
found strong noise-plasticity correlations for most gene groups in Arabidopsis;
additionally, promoter architecture, functional essentiality of genes, and
circadian rhythm appeared to have only a weak influence on the correlation
strength. The differences in the characteristics of noise-plasticity correlations
may result from three-dimensional chromosomal structures and/or circadian rhythm.
PMID- 26431772
TI - Bifurcations analysis of oscillating hypercycles.
AB - We investigate the dynamics and transitions to extinction of hypercycles governed
by periodic orbits. For a large enough number of hypercycle species (n>4) the
existence of a stable periodic orbit has been previously described, showing an
apparent coincidence of the vanishing of the periodic orbit with the value of the
replication quality factor Q where two unstable (non-zero) equilibrium points
collide (named QSS). It has also been reported that, for values below QSS, the
system goes to extinction. In this paper, we use a suitable Poincare map
associated to the hypercycle system to analyze the dynamics in the bistability
regime, where both oscillatory dynamics and extinction are possible. The stable
periodic orbit is identified, together with an unstable periodic orbit. In
particular, we are able to unveil the vanishing mechanism of the oscillatory
dynamics: a saddle-node bifurcation of periodic orbits as the replication quality
factor, Q, undergoes a critical fidelity threshold, QPO. The identified
bifurcation involves the asymptotic extinction of all hypercycle members, since
the attractor placed at the origin becomes globally stable for values Q0.056) except the mean of C.
polykomos (p<0.05). The mean, SD, High5 of CB DBM at M2 of C. atys was
significantly higher than those of C. polykomos and P. badius (p<0.006).
CONCLUSIONS: The durophagous C. atys had higher CB DBM value at the M2 region
than C. polykomos and P. badius, which supports the hypothesis that materially
stiffer mandibular bone in C. atys can develop in response to the generation of
high bite forces during hard object feeding.
PMID- 26431829
TI - The evaluation of 7 commercial real-time PCR kits for Zaire ebolavirus using
virus-like particle-encapsulated EBOV RNA.
AB - Several Chinese commercial real-time PCR kits for Zaire ebolavirus have been
developed after the Ebola outbreak and used by Chinese medical teams in West
Africa. In order to know the essential performance indicators of these kits,
analytical sensitivity and precision were evaluated with virus-like particle
(VLP)-encapsulated EBOV RNA. The limit of detection (LOD) and the precision were
completed with a series of VLPs. The maximum and minimum of LOD was acquired by
ZJ BioTech and Daan gene, respectively. For precision, all of the detection
results were <5% except the maximum 5.17%. Among them, Puruikang, Daan gene,
Sansure, ZJ BioTech, and Huada demonstrated superior reproducibility. Overall,
the requirements of LOD <1000 copies/mL and coefficient of variation <5% could be
satisfied by all kits except Kehua. Meanwhile, it is feasible for VLPs as a
substitute of positive samples in assay evaluation.
PMID- 26431830
TI - Molecular characterization of Staphylococcus aureus isolates carrying the Panton
Valentine leukocidin genes from Rio de Janeiro hospitals.
AB - In a collection of 50 pvl-positive Staphylococcus aureus isolates from 10 Rio de
Janeiro hospitals, 18 (36%) were from bloodstream infections, and 31 (62%)
carried the SCCmec IV. Among 25 (50%) isolates of the USA1100/ST30/CC30 lineage
present in 8 hospitals, 1 isolate was characterized as vancomycin-intermediate S.
aureus.
PMID- 26431831
TI - Leisure-time, occupational, and commuting physical activity and risk of type 2
diabetes in Japanese workers: a cohort study.
AB - BACKGROUND: Physical activity has been suggested to reduce the risk of type 2
diabetes. However, evidence is limited regarding whether vigorous-intensity
activity yields the same benefits in preventing type 2 diabetes compared with an
equivalent dose of moderate-intensity activity as well as other type of physical
activity. We examined the risk of type 2 diabetes associated with exercise
intensity during leisure and occupational and commuting physical activity among
Japanese individuals. METHODS: Participants included 26,628 workers (23,207 men
and 3,421 women) aged 30 to 64 years without diabetes at baseline. There was 6
years of follow-up maximum. Leisure-time exercise, occupational physical
activity, and duration of walking to and from work were self-reported. Diabetes
was diagnosed by using HbA1c, fasting or random blood glucose, and self-report.
We used Cox regression analysis to estimate the hazard ratio (HR) and the 95%
confidence interval (CI) of incident diabetes. RESULTS: During a mean follow-up
of 5.2 years, 1,770 participants developed type 2 diabetes. Compared with
individuals who engaged in no exercise, the HRs (95% CIs) for <7.5, 7.5 to <15.0,
and >=15.0 MET-hours per week of exercise were 0.94 (0.81, 1.08), 1.07 (0.88,
1.30), and 0.90 (0.67, 1.21), respectively, among individuals who engaged in
moderate-intensity exercise alone; 0.68 (0.44, 1.06), 0.86 (0.54, 1.34), and 0.89
(0.56, 1.41), respectively, among individuals who engaged in vigorous-intensity
exercise alone; and 0.70 (0.44, 1.11), 0.57 (0.37, 0.90), and 0.76 (0.52, 1.11),
respectively, among individuals who engaged in the two intensities, with
adjustments for potential confounders and the total volume of exercise.
Occupational physical activity and walking to and from work were not associated
with diabetes. CONCLUSIONS: The results suggest that vigorous-intensity exercise
can reduce the risk of type 2 diabetes among Japanese workers.
PMID- 26431832
TI - Guanosine inhibits LPS-induced pro-inflammatory response and oxidative stress in
hippocampal astrocytes through the heme oxygenase-1 pathway.
AB - Guanosine, a guanine-based purine, is an extracellular signaling molecule that is
released from astrocytes and has been shown to promote central nervous system
defenses in several in vivo and in vitro injury models. Our group recently
demonstrated that guanosine exhibits glioprotective effects in the C6 astroglial
cell line by associating the heme oxygenase-1 (HO-1) signaling pathway with
protection against azide-induced oxidative stress. Astrocyte overactivation
contributes to the triggering of brain inflammation, a condition that is closely
related to the development of many neurological disorders. These cells sense and
amplify inflammatory signals from microglia and/or initiate the release of
inflammatory mediators that are strictly related to transcriptional factors, such
as nuclear factor kappa B (NFkappaB), that are modulated by HO-1. Astrocytes also
express toll-like receptors (TLRs); TLRs specifically recognize
lipopolysaccharide (LPS), which has been widely used to experimentally study
inflammatory response. This study was designed to understand the glioprotective
mechanism of guanosine against the inflammatory and oxidative damage induced by
LPS exposure in primary cultures of hippocampal astrocytes. Treatment of
astrocytes with LPS resulted in deleterious effects, including the augmentation
of pro-inflammatory cytokine levels, NFkappaB activation, mitochondrial
dysfunction, increased levels of oxygen/nitrogen species, and decreased levels of
antioxidative defenses. Guanosine was able to prevent these effects, protecting
the hippocampal astrocytes against LPS-induced cytotoxicity through activation of
the HO-1 pathway. Additionally, the anti-inflammatory effects of guanosine were
independent of the adenosinergic system. These results highlight the potential
role of guanosine against neuroinflammatory-related diseases.
PMID- 26431834
TI - [Unilateral visual impairment and conspicuous optical coherence tomography in a
23-year-old woman].
PMID- 26431833
TI - ATP release, generation and hydrolysis in exocrine pancreatic duct cells.
AB - Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via
P2Y and P2X receptors. It is well known that ATP is released from upstream
pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete
bicarbonate-rich fluid, has not yet been examined. First, our aim was to reveal
whether pancreatic duct cells release ATP locally and whether they enzymatically
modify extracellular nucleotides/sides. Second, we wished to explore which
physiological and pathophysiological factors may be important in these processes.
Using a human pancreatic duct cell line, Capan-1, and online luminescence
measurement, we detected fast ATP release in response to pH changes, bile acid,
mechanical stress and hypo-osmotic stress. ATP release following hypo-osmotic
stress was sensitive to drugs affecting exocytosis, pannexin-1, connexins, maxi
anion channels and transient receptor potential cation channel subfamily V member
4 (TRPV4) channels, and corresponding transcripts were expressed in duct cells.
Direct stimulation of intracellular Ca(2+) and cAMP signalling and ethanol
application had negligible effects on ATP release. The released ATP was
sequentially dephosphorylated through ecto-nucleoside triphosphate
diphosphohydrolase (NTPDase2) and ecto-5'-nucleotidase/CD73 reactions, with
respective generation of adenosine diphosphate (ADP) and adenosine and their
maintenance in the extracellular medium at basal levels. In addition, Capan-1
cells express counteracting adenylate kinase (AK1) and nucleoside diphosphate
kinase (NDPK) enzymes (NME1, 2), which contribute to metabolism and regeneration
of extracellular ATP and other nucleotides (ADP, uridine diphosphate (UDP) and
uridine triphosphate (UTP)). In conclusion, we illustrate a complex regulation of
extracellular purine homeostasis in a pancreatic duct cell model involving: ATP
release by several mechanisms and subsequent nucleotide breakdown and ATP
regeneration via counteracting nucleotide-inactivating and nucleotide
phosphorylating ecto-enzymes. We suggest that extracellular ATP homeostasis in
pancreatic ducts may be important in pancreas physiology and potentially in
pancreas pathophysiology.
PMID- 26431835
TI - What Do Molecular Tests Add to Prognostic Stratification in MF: Is It Time to Add
These to Our Clinical Practice?
AB - The molecular landscape of patients with myelofibrosis (MF) includes "phenotypic
driver" and "subclonal" mutations. The three driver (JAK2, MPL and CALR)-mutated
genes currently represent major diagnostic criteria, unlike subclonal mutations
that are not specific for the disease and occur in other myeloid neoplasms.
Recent data indicate that selected mutations deserve prognostic significance
allowing to identify categories of patients with different survival and risk of
leukemia. This review focuses on current knowledge regarding genotype-prognostic
correlates in MF, however, with the understanding that this is a rapid moving
field and no definite recommendations for the clinicians can be done yet.
PMID- 26431837
TI - [Update on extracorporeal photopheresis].
AB - Extracorporeal photopheresis (ECP) is a treatment approach that combines
leukapheresis with photochemotherapy and is derived from PUVA; with this
procedure, nucleated cells such as lymphocytes and monocytes are extracorporeally
irradiated with UVA light after photosensitization. ECP is an effective treatment
modality with few side effects that in recent years has been expanded to treat a
range of indications. It has been proven effective in the treatment of cutaneous
T cell lymphoma and is being increasing used in other lymphocyte-mediated,
autoimmune and inflammatory diseases that are associated with proliferation of
autoreactive T cells.
PMID- 26431836
TI - Molecular Pathogenesis of Peripheral T Cell Lymphoma.
AB - Understanding the molecular pathogenesis of peripheral T cell lymphomas (PTCLs)
has lagged behind that of B cell lymphomas due to disease rarity. However, novel
approaches are gradually clarifying these mechanisms, and gene profiling has
identified specific signaling pathways governing PTCL cell survival and growth.
For example, genetic alterations have been discovered, including signal
transducer and activator of transcription (STAT)3 and STAT5b mutations in several
PTCLs, disease-specific ras homolog family member A (RHOA) mutations in
angioimmunoblastic T cell lymphoma (AITL), and recurrent translocations at the
dual specificity phosphatase 22 (DUSP22) locus in anaplastic lymphoma receptor
tyrosine kinase (ALK)-negative anaplastic large cell lymphomas (ALCLs).
Intriguingly, some PTCL-relevant mutations are seen in apparently normal blood
cells as well as tumor cells, while others are confined to tumor cells. These
data have dramatically changed our understanding of PTCL origins: once considered
to originate from mature T lymphocytes, some PTCLs are now believed to emerge
from immature hematopoietic progenitor cells.
PMID- 26431838
TI - [Pigmented macule on the neck, red nodules on the trunk. Diagnosis: neck left:
Melanoma. Pectoral right: Breast cancer].
PMID- 26431839
TI - Alpha-Lipoic Acid Attenuates Oxidative Damage in Organs After Sepsis.
AB - Sepsis progression is linked with the imbalance between reactive oxygen species
and antioxidant enzymes. Thus, the aim of this study was to evaluate the effect
of alpha-lipoic acid (ALA), a powerful antioxidant, in organs of rats submitted
to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation puncture
(CLP) and treated with ALA or vehicle. After CLP (12 and 24 h), the
myeloperoxidase (MPO) activity, protein and lipid oxidative damage, and
antioxidant enzymes in the liver, kidney, heart, and lung were evaluated. ALA was
effective in reducing MPO activity, lipid peroxidation in the liver, and protein
carbonylation only in the kidney in 12 h after CLP. In 12 h, SOD activity
increased in the kidney and CAT activity in the liver and kidney with ALA
treatment. Thus, ALA was able to reduce the inflammation and oxidative stress in
the liver and kidney after sepsis in rats.
PMID- 26431840
TI - Tafluprost/Timolol: A Review in Open-Angle Glaucoma or Ocular Hypertension.
AB - A once-daily preservative-free fixed combination ophthalmic solution containing
tafluprost 0.0015 % and timolol 0.5 % (hereafter referred to as
tafluprost/timolol) [Taptiqom((r))] has been developed to lower intraocular
pressure (IOP) whilst avoiding damage to the ocular surface associated with
preservatives such as benzalkonium chloride. Tafluprost/timolol is available in
various EU countries for the reduction of IOP in adults with open-angle glaucoma
or ocular hypertension who are insufficiently responsive to topical monotherapy
with beta-adrenergic receptor antagonists or prostaglandin analogues and require
a combination therapy, and who would benefit from preservative-free eye drops. In
two multinational, phase III studies, tafluprost/timolol was superior to
monotherapy with either preservative-free tafluprost 0.0015 % once daily or
preservative-free timolol 0.5 % twice daily, and noninferior to concomitant
therapy with preservative-free tafluprost 0.0015 % once daily plus preservative
free timolol 0.5 % twice daily in lowering IOP in adults with open-angle glaucoma
or ocular hypertension. Tafluprost/timolol was well tolerated in these studies,
with a tolerability profile consistent with that of its individual components and
with no new adverse reactions observed. Thus, preservative-free fixed combination
tafluprost/timolol is an effective treatment option for the reduction of IOP in
adults with open-angle glaucoma or ocular hypertension, providing a useful
alternative for those patients who would benefit from preservative-free eye
drops.
PMID- 26431841
TI - Artificial urinary sphincter implantation in women with stress urinary
incontinence: preliminary comparison of robot-assisted and open approaches.
AB - INTRODUCTION AND HYPOTHESIS: We aimed to compare outcomes of open and robot
assisted artificial urinary sphincter (AUS) implantation in female patients.
METHODS: The charts of all female patients who underwent an AUS implantation
between 2008 and 2014 in a single center were retrospectively reviewed. From 2008
to 2012, AUS were implanted using an open approach and from 2013 to 2014 using a
robot-assisted approach. Perioperative and functional parameters were compared
between groups. The primary endpoint was continence status. RESULTS: Twenty-four
women were assessed: 16 in the open group and eight in the robot-assisted group.
Three patients had neurogenic stress urinary incontinence. Most patients had
undergone previous procedures for urinary incontinence (15 in the open group and
seven in the robotic group). Mean operative time was similar in both groups (214
vs. 211 min; p = 0.90). Postoperative complicationsrate was lower in the robot
assisted group (25 vs. 75 %; p = 0.02). There was a trend toward a lower
intraoperative complication rate (37.5 vs. 62.5 %; p = 0.25), decreased blood
loss (17 ml vs. 275 ml; p = 0.22), and shorter length of stay (3.5 vs. 9.3 days;
p = 0.09) in the robot-assisted group. Continence rates were comparable in both
groups (75 vs. 68.8 %; p = 0.75). Three AUS explantations were needed in the open
group (18.8 %) compared with one in the robot-assisted group (12.5 %; p = 0.70).
CONCLUSIONS: In female patients, the robot-assisted approach compared with open
AUS implantation could decrease intraoperative and postoperative complication
rates, length of hospital stay, and blood loss.
PMID- 26431842
TI - The "learning curve" for retropubic mid-urethral sling procedures: a
retrospective cohort study.
AB - INTRODUCTION AND HYPOTHESIS: Mid-urethral tape procedures brought a paradigm
shift in surgery for stress incontinence; little research into the development
and maintenance of surgical competence for the procedure exists. The hypothesis
behind this study is that the "learning curve" for retropubic mid-urethral sling
procedures, judged by the surrogate of bladder perforation, is longer than
previously thought. METHODS: This was a retrospective single-centre database and
case note review of retropubic mid-urethral tape procedures. Unadjusted rates of
bladder perforation, operating time, postoperative voiding difficulty, tape
extrusion, and patient reported outcome were calculated; progress was evaluated
using the cumulative sum method. Outcomes were assessed for 1 consultant, 2
subspecialty trainees (fellows), 7 advanced training skills module (ATSM)
trainees (senior residents) and 6 core specialty trainees (residents) in years 4
7 of training. RESULTS: A total of 1,568 women were identified as having mid
urethral tape procedures; 568 (36 %) had additional procedures concurrently; 259
(20 %) were secondary procedures. The overall perforation rate for individual
surgeons varied between 0 and 31 % and averaged 10.3 % amongst the core and ATSM
trainees (a mean of 11 procedures), 4.5 % amongst the subspecialty trainees (a
mean of 66 procedures) and 1.3 % for the consultant (1,284 procedures). The
number of perforations for individual surgeons peaked at between 10 and 30
procedures undertaken. The number of cases performed to reach a target level of
<= 5 % perforations varied between 20 and 80. CONCLUSIONS: Whilst seductively
simple in concept, mid-urethral tape procedures are not without risk; their
inherently "blind" nature makes them difficult to teach. The "learning curve" to
independent practice may be longer than previously considered.
PMID- 26431843
TI - [Not Available].
PMID- 26431844
TI - Smoking rates in UK continue to fall.
PMID- 26431845
TI - Using subscales when scoring the Cushing's quality of life questionnaire.
AB - CONTEXT: Patients in long-term remission of Cushing's syndrome (CS) commonly
report impaired quality of life (QoL). The CushingQoL questionnaire is a disease
specific QoL questionnaire for patients diagnosed with CS. The developers of the
CushingQoL recommend using a global (total) score to assess QoL. However, the
global score does not capture all aspects of QoL as outlined by the World Health
Organization (WHO). OBJECTIVE: The aim of the study was to compare the
performance of different scoring options to determine the optimal method for the
CushingQoL. DESIGN AND PATIENTS: Patients in remission from CS (n=341) were
recruited from the Cushing's Syndrome Research Foundation's email listserv and
Facebook page, and asked to complete the CushingQoL and a short demographics
survey. RESULTS: Using an exploratory analysis, adequate model fit was obtained
for the global score, as well as a 2-subscale (psychosocial issues and physical
problems) scoring solution. Confirmatory methods were performed to identify the
optimal scoring solution. Both the global score and the 2-subscale scoring
solution showed adequate model fit. However, a chi(2) difference test indicated
that the 2-subscale scoring solution was a significantly better fit than the
global score (P<0.05). CONCLUSION: If doctors or researchers would like to tease
apart physical and psychosocial issues, the 2-subscale scoring solution would be
recommended, since this solution showed to be optimal in scoring the CushingQoL.
Regardless of the scoring solution used, the CushingQoL has proven to be a
valuable resource for assessing health-related QoL in patients with CS.
PMID- 26431846
TI - Guideline recommended treatments in complex patients with multimorbidity.
PMID- 26431847
TI - Effectiveness of evidence-based medicine on knowledge, attitudes, and practices
of family planning providers: a randomized experiment in Jordan.
AB - BACKGROUND: Provider misconceptions and biases about contraceptive methods are
major barriers to family planning access for women in low- and middle-income
countries, including Jordan. Evidence-Based Medicine (EBM) programs aim to reduce
biases and misconceptions by providing doctors with the most up-to-date
scientific evidence on contraceptive methods. METHODS: We evaluate the effects of
an EBM program conducted in Jordan on private providers' knowledge, attitudes,
and practices. Family planning providers randomly assigned to a treatment group
were invited to attend a roundtable seminar on the injectable contraceptive Depot
Medroxy Progesterone Acetate (DMPA), and to receive two 15 min one-on-one
educational visits that reinforce the messages from the seminar. RESULTS: There
was low compliance with the EBM program. The study fails to detect an impact on
providers' knowledge of DMPA's side effects or on reported clinical practices.
There is suggestive evidence of a positive impact on providers' attitudes toward
and confidence in prescribing the contraceptive to their patients. There is also
evidence of positive selection into program participation. CONCLUSIONS: We
conclude that EBM may not be effective as a stand-alone program targeting a
family planning method with a high level of provider and consumer bias. Evidence
of positive selection into program participation underscores the importance of
randomization to avoid overestimating the true effects of interventions. TRIAL
REGISTRATION: AEA RCT Registry, AEARCTR0000539 , 11/3/2014.
PMID- 26431848
TI - Prevalence of pregnancy induced hypertension and pregnancy outcomes among women
seeking maternity services in Harare, Zimbabwe.
AB - BACKGROUND: Pregnancy induced hypertension (PIH) is one of the most common causes
of both maternal and neonatal morbidity, affecting about 5 - 8 % of pregnant
women. It is associated with adverse pregnancy outcomes as well as maternal
morbidity and mortality. Harare City experienced an increase in referrals due to
PIH to central hospitals from 2009 to 2011. We conducted a study to determine the
prevalence of PIH and pregnancy outcomes among women with PIH. METHODS: An
analytic cross sectional study was conducted. Interviewer administered
questionnaires were used to capture demographic data, obstetric history and
knowledge on PIH management. Records were reviewed for pregnancy outcomes while
key informants were also interviewed on patient management. RESULTS: PIH
prevalence was 19.4 %. Women with PIH were three times more likely to deliver a
low birth weight baby (OR 3.00, p = 0.0115), 4.3 times more likely to have still
birth (OR 4.34, p = 0.0517) and four times more likely to have a baby with low
Apgar score at 5 minutes (OR 4.47, p = 0.0155) compared to women without PIH.
There was no statistically significant difference in delivery before 37 weeks
gestation between women with PIH and those without (OR 1.70, p = 0.1251). 12,5 %
of the women delivered by caesarean section. Methyldopa was the drug of choice
for management of PIH. Less than half of the health workers had sufficient
knowledge on definition or management of PIH. Delay in seeking care and shortage
of resources were the major reported challenges in the proper management of PIH.
CONCLUSION: PIH prevalence was high. Women with PIH were at higher risk of
adverse pregnancy outcomes than those without. Poor knowledge of management of
PIH and inadequate resources are a threat to the proper management of PIH. This
underscores the need for increased human resources and capacity building as well
as resource mobilisation for proper management of pregnant women. Urinalysis must
be routinely done for all pregnant women regardless of their blood pressure.
PMID- 26431849
TI - Nitroreductase gene-directed enzyme prodrug therapy: insights and advances toward
clinical utility.
AB - This review examines the vast catalytic and therapeutic potential offered by type
I (i.e. oxygen-insensitive) nitroreductase enzymes in partnership with
nitroaromatic prodrugs, with particular focus on gene-directed enzyme prodrug
therapy (GDEPT; a form of cancer gene therapy). Important first indications of
this potential were demonstrated over 20 years ago, for the enzyme-prodrug
pairing of Escherichia coli NfsB and CB1954 [5-(aziridin-1-yl)-2,4
dinitrobenzamide]. However, it has become apparent that both the enzyme and the
prodrug in this prototypical pairing have limitations that have impeded their
clinical progression. Recently, substantial advances have been made in the
biodiscovery and engineering of superior nitroreductase variants, in particular
development of elegant high-throughput screening capabilities to enable
optimization of desirable activities via directed evolution. These advances in
enzymology have been paralleled by advances in medicinal chemistry, leading to
the development of second- and third-generation nitroaromatic prodrugs that offer
substantial advantages over CB1954 for nitroreductase GDEPT, including greater
dose-potency and enhanced ability of the activated metabolite(s) to exhibit a
local bystander effect. In addition to forging substantial progress towards
future clinical trials, this research is supporting other fields, most notably
the development and improvement of targeted cellular ablation capabilities in
small animal models, such as zebrafish, to enable cell-specific physiology or
regeneration studies.
PMID- 26431850
TI - miR-429 regulates alveolar macrophage inflammatory cytokine production and is
involved in LPS-induced acute lung injury.
AB - p38 MAPK (mitogen-activated protein kinase) is a critical regulator in lung
inflammation. It can be inactivated by DUSP1 (dual-specificity phosphatase 1)
which was identified as a putative target of miR-429. miR-429 mimics directly
targeted to the 3'-UTR of the gene encoding DUSP1 may result in the translational
attenuation of DUSP1. Moreover, the phosphorylation of p38 MAPK was prolonged
after miR-429 mimic treatment. Additionally, miR-429 expression was sensitive to
LPS (lipopolysaccharide) stimulation and the miR-429 mimics increased the
production of pro-inflammatory cytokines. However, anti-miR-429 reduced the LPS
induced production of pro-inflammatory cytokines. These results provide direct
evidence that miR-429 is involved in the LPS-induced inflammatory response. In
parallel with miR-429, miR-200b and miR-200c, but not miR-200a or miR-141, shared
similar effects. In vivo, LPS induced the expression of miR-429, miR-200b and miR
200c in lung. At the same time, inhibiting these miRNAs by anti-miRNAs attenuated
the LPS-induced pulmonary inflammatory response and injury. These findings reveal
that miR-429 possesses pro-inflammatory activities and may be a potential therapy
target for LPS-induced lung injury.
PMID- 26431851
TI - Preoperative pulse and thermal radiofrequency facilitates prehabilitation and
subsequent rehabilitation of a patient scheduled for total knee arthroplasty.
PMID- 26431852
TI - Opioid information pamphlet increases postoperative opioid disposal rates: a
before versus after quality improvement study.
AB - PURPOSE: Half of postoperative patients are prescribed an opioid, but a majority
do not store or dispose of them properly thus risking diversion. We examined the
efficacy of an opioid educational pamphlet addressing opioid weaning, storage,
and disposal. We hypothesized that the pamphlet would increase the rate of proper
opioid disposal, storage, and weaning. METHODS: This prospective before and after
study was conducted at UBC Hospital in primary total hip or knee arthroplasty
patients. Adults with American Society of Anesthesiologists physical class I-III,
with no addiction history and consuming <= 30 mg of morphine equivalents daily
were enrolled in the study. Two groups received similar standard management,
except the intervention group additionally received the opioid education
pamphlet. Patients were contacted four weeks postoperatively to complete a
survey. The primary endpoint was to evaluate proper opioid disposal rates.
Secondary endpoints were to evaluate opioid storage and weaning rates. RESULTS:
Two hundred twenty-six patients were enrolled and 172 (76%) completed the survey.
Among patients who had discontinued opioids, rates of proper disposal increased
from 2/42 (5%) to 12/45 (27%) in those receiving the pamphlet (difference in
proportions, 22%; 95% confidence interval (CI), 5 to 38; P = 0.005). Secure
opioid storage did not improve in those receiving the opioid pamphlet [before,
18/86 (21%) vs after, 20/86 (23%); difference in proportions, 3%; 95% CI, -11 to
15; P = 0.713]. The proportion of patients weaned from opioids was unchanged by
the pamphlet [before, 42/86 (49%) vs after, 45/86 (52%); P = 0.735]. CONCLUSION:
The introduction of an education pamphlet significantly improved self-reported
proper opioid disposal rates in postoperative patients.
PMID- 26431853
TI - Antithrombin activity and heparin response in neonates and infants undergoing
congenital cardiac surgery: a retrospective cohort study.
AB - PURPOSE: The immature coagulation system during infancy has age-related
physiological differences in proteins that contribute to significant variation in
heparin responsiveness through alterations in heparin-enhanced thrombin
inhibition. The primary aim of this study was to evaluate the relationship
between preoperative antithrombin (AT) activity and heparin responsiveness in
neonates and infants undergoing congenital cardiac surgery. METHODS: In this
retrospective cohort study, neonates (aged 0-28 days) and infants (aged 29-365
days) undergoing congenital cardiac surgery in the 12-month period from October
2013 to 2014 were studied. The two age groups were compared for the primary
endpoint of heparin response measured by the heparin sensitivity index (HSI),
with heparin loading doses and heparin resistance being secondary endpoints.
Multivariable linear regression analyses were used to explore the relationship
between AT activity and heparin response measured by HSI. RESULTS: There were 122
infants and 19 neonates included in the study. After adjusting for low-molecular
weight heparin, unfractionated heparin, and platelet count, there was a
significant relationship between AT activity and HSI (r = 0.44; P = 0.009). The
median [interquartile range] HSI did not differ between neonates and infants
(0.76 [0.69- 0.98] vs 0.89 [0.70-1.10] sec.unit(-1).kg(-1), respectively; median
difference, 0.08; 95% confidence interval [CI], -0.01 to 0.17; P = 0.182),
despite the mean (standard deviation) AT activity differing between age groups
[60 (16)% vs 84 (18)%, respectively; mean difference, 24; 95% CI, 15 to 32; P <
0.001]. CONCLUSIONS: There was a moderate relationship between AT activity and
heparin response measured by HSI. Comparing neonates and infants, there was
similar heparin responsiveness measured by HSI despite differing AT activity
levels. These findings should help guide the perioperative administration of
exogenous AT to neonates and infants and suggest that, outside the neonatal
period, preoperative AT activity may be used to identify children at risk of
decreased heparin responsiveness.
PMID- 26431854
TI - A randomized trial comparing axillary block versus targeted intracluster
injection supraclavicular block for upper limb surgery.
AB - PURPOSE: This randomized trial aimed to validate a new method for brachial plexus
blockade, i.e., targeted intracluster injection supraclavicular block (TII SCB),
by comparing it with ultrasound-guided axillary block (AXB). We hypothesized that
TII SCB would result in a shorter total anesthesia-related time. METHODS: Forty
patients undergoing upper limb surgery were randomized to ultrasound-guided TII
SCB (n = 20) or AXB (n = 20). In the TII SCB group, we deposited 16 mL of
lidocaine 1.5% with epinephrine 5 ug.mL(-1) into the largest neural cluster
(i.e., brachial plexus trunks/divisions). Subsequently, an additional 16 mL was
divided into equal aliquots and injected inside each satellite cluster. In the
AXB group, 5.5 mL were deposited around the musculocutaneous nerve and 23.5 mL
were injected at the 6 o'clock position of the axillary artery. The main outcome
for comparison between the two groups was the total anesthesia-related time
(defined as the sum of block performance and onset times). We also recorded the
number of needle passes, procedural pain, and complications (vascular puncture,
paresthesia). RESULTS: The TII SCB method provided a quicker mean (SD) onset time
compared with the AXB group [9.5 (5.8) min vs 18.9 (6.1) min; mean difference,
9.5 min; 99% CI, -14.7 to -4.2; P < 0.001] and a shorter mean (SD) total
anesthesia-related time [20.1 (5.0) min vs 27.2 (6.5) min; mean difference, -7.0
min; 95% CI, -10.9 to -3.1; P = 0.001]. There were no intergroup differences in
terms of success rate (95%), procedural pain, vascular puncture and paresthesia.
The AXB group displayed a faster performance time [8.2 (1.6) min vs 10.6 (2.6)
min; P = 0.001] with fewer median [interquartile range] needle passes (3 [2-6] vs
5 [4-8]; P < 0.001). CONCLUSION: Ultrasound-guided TII SCB provides a quicker
onset and a shorter total anesthesia-related time than ultrasound-guided AXB.
PMID- 26431855
TI - Determination of ciprofloxacin and levofloxacin in human sputum collected from
cystic fibrosis patients using microextraction by packed sorbent-high performance
liquid chromatography photodiode array detector.
AB - This paper reports a new, easy, cheap, and fast MEPS-HPLC-PDA method for the
simultaneous analysis of ciprofloxacin and levofloxacin, two fluoroquinolones
(FLQs) commonly used for the treatment of pulmonary infections in cystic fibrosis
(CF) patients. The FLQs were resolved on a Discovery C8 column (250mm*4.6mm; 5MUm
particle size) using an isocratic elution with a run time of 15min, without
further purification. The method was validated over concentrations ranging from
0.05 to 2MUg/mL for both analytes in human sputum, and enrofloxacin was used as
internal standard. This method was successfully tested to detect FLQs in sputum
collected from CF patients. The MEPS-HPLC-PDA method was validated using
biological samples collected from CF patients orally or intravenously injected
with FLQs. The resultant data showed that the method is selective, sensitive and
robust over range of concentrations for both FLQs. The limit of quantification of
the method was 0.05MUg/mL for both analytes (comparable to more complex and
expensive instrument configurations), weighted-matrix-matched standard curves
showed a good linearity up to 2MUg/mL, and parallelism tests were also
successfully assessed. The intra- and inter-day precision (RSD%) values were
<=10.4% and <=11.1%, respectively, for all range of analysis. The intra- and
inter-day trueness (Bias%) values are ranged from -11.8% to 7.25% for both
antibiotic drugs. At the best of our knowledge, this is the first MEPS-HPLC-PDA
based method that uses MEPS procedure for simultaneous determination of
ciprofloxacin and levofloxacin in human sputum. The method was tested
successfully on real sputum samples by following a conventional drug
administration. Furthermore, the MEPS-HPLC-PDA based method provides more
advantages to detect and analyze quickly the antibiotic drugs in biological
matrices than other analytical procedures reported in literature.
PMID- 26431856
TI - Rapid and sensitive multiresidue analysis of pesticides in tobacco using low
pressure and traditional gas chromatography tandem mass spectrometry.
AB - Public exposure to pesticide residues through the main/side-stream smoke of
tobacco (Nicotiana tabacum L.) is an international concern. This article reports
optimization and validation of large-scale multiresidue analysis methods
involving low pressure and traditional gas chromatography tandem mass
spectrometry in compliance with the guidance residue levels (GRLs) of Cooperative
Centre for Scientific Research Relative to Tobacco (CORESTA). Analysis by low
pressure GC-MS/MS offered three times rapid turn around time over the traditional
GC-MS/MS with limits of quantifications (LOQs) less than 2MUg/L for all the 259
test compounds and the recoveries in the range of 70-118% (+/-20%) at 10 and
20MUg/kg levels of fortification.
PMID- 26431857
TI - Development and validation of a high performance liquid chromatographic-mass
spectrometry method for the simultaneous quantification of 10 trichothecenes in
ultra-high temperature processed cow milk.
AB - An LC-MS/MS (QqQ) method has been developed and validated for simultaneous
determination of the following trichothecenes in UHT cow milk: nivalenol (NIV),
deoxynivalenol (DON), deepoxy-deoxynivalenol (DOM-1), 3-acetyldeoxynivalenol (3
ADON), 15-acetyldeoxynivalenol (15-ADON), neosolaniol (NEO), diacetoxyscirpenol
(DAS), fusarenon X (FUS-X), T-2 and HT-2 toxins. Sample treatment is simple and
based on the extraction with acetonitrile (ACN), acidified with 0.2% formic acid,
followed by a purification process, adding sodium acetate to the ACN/water
extract in order to separate aqueous phase and, consequently, polar components of
the milk. Validation of the method for all the 10 mycotoxins was successful;
validation parameters taken into account were as follows: limits of detection
(LOD) and quantification (LOQ), linearity, precision (within-day and between-day
variability), recovery, matrix effect and stability. The LODs were 10.1, 2.5,
1.5, 1.9, 0.1, 0.5, 1.0, 0.08, 0.4 and 0.05ng/mL for NIV, DON, DOM-1, FUS-X, NEO,
3-ADON, 15-ADON, DAS, HT-2 and T-2, respectively. Mean recovery values (obtained
in intermediate precision conditions) were between 63.5 and 75.8 (RSDR<=15%) for
all the mycotoxins. All the mycotoxins suffered from matrix effects, especially
DON.
PMID- 26431858
TI - Solvent modulated linear pH gradient elution for the purification of conventional
and bispecific antibodies: Modeling and application.
AB - Classical ion-exchange chromatography using a linear salt gradient to elute the
adsorbed protein at fixed pH is the most common method to separate product
related impurities during downstream processing of biopharmaceuticals. Linear pH
gradient elution provides a useful alternative by separating proteins in a linear
pH gradient at fixed salt concentration. Although linear pH gradient elution
provides excellent selectivity, it is rarely encountered in industrial
purification processes. Here, a stoichiometric displacement model is used to
characterize pH gradient elution based on simple linear gradient elution
experiments. Protein retention behavior is described with respect to the pH
dependencies of the characteristic binding charge and the equilibrium constant of
the ion exchange reaction. Furthermore, the influence of solvent composition
using PEG as a mobile phase modifier is investigated. Validity and applicability
of the model are demonstrated for the purification of a conventional monoclonal
antibody from soluble aggregates and for a novel bispecific antibody format
containing a unique product-related impurity profile. pH step elution protocols
are derived from model calculations without further optimization experiments
necessary.
PMID- 26431859
TI - Automated harvesting and 2-step purification of unclarified mammalian cell
culture broths containing antibodies.
AB - Therapeutic monoclonal antibodies represent one of the fastest growing segments
in the pharmaceutical market. The growth of the segment has necessitated
development of new efficient and cost saving platforms for the preparation and
analysis of early candidates for faster and better antibody selection and
characterization. We report on a new integrated platform for automated harvesting
of whole unclarified cell-culture broths, followed by in-line tandem affinity
capture, pH neutralization and size-exclusion chromatography of recombinant
antibodies expressed transiently in mammalian human embryonic kidney 293T-cells
at the 1-L scale. The system consists of two bench-top chromatography instruments
connected to a central unit with eight disposable filtration devices used for
loading and filtering the cell cultures. The staggered parallel multi-step
configuration of the system allows unattended processing of eight samples in less
than 24h. The system was validated with a random panel of 45 whole-cell culture
broths containing recombinant antibodies in the early profiling phase. The
results showed that the overall performances of the preparative automated system
were higher compared to the conventional downstream process including manual
harvesting and purification. The mean recovery of purified material from the
culture-broth was 66.7%, representing a 20% increase compared to that of the
manual process. Moreover, the automated process reduced by 3-fold the amount of
residual aggregates in the purified antibody fractions, indicating that the
automated system allows the cost-efficient and timely preparation of antibodies
in the 20-200mg range, and covers the requirements for early in vitro and in vivo
profiling and formulation of these drug candidates.
PMID- 26431860
TI - Environmental friendly method for urban wastewater monitoring of micropollutants
defined in the Directive 2013/39/EU and Decision 2015/495/EU.
AB - The fate and removal of organic micropollutants in the environment is a demanding
issue evidenced by the recent European policy. This work presents an analytical
method for the trace quantification of 37 micropollutants including Priority
Substances (Directive 2013/39/EU), substances of the recent watch list (Decision
2015/495/EU) and contaminants of emerging concern: pesticides, multi-class
pharmaceuticals and a metabolite, estrogens and one industrial compound. The
analytical method was based on solid phase extraction (SPE) followed by ultra
high performance liquid chromatography with tandem mass spectrometry (UHPLC
MS/MS), using eco-friendly solvents (ethanol and ultrapure water) both in the SPE
and UHPLC, according to green analytical chemistry principles. Briefly,
Oasis((r)) HLB cartridges were used to preconcentrate 100mL of water samples and
the reconstituted extracts were analyzed with a KinetexTM column under reversed
mode, the linear ranges extended to 200ngL(-1) (R(2)>0.99) for all the analytes.
The method detection limits were between 0.04 and 2.26ngL(-1) and the method
quantification limits were between 0.13 and 6.85ngL(-1). The identity of the
compounds was confirmed using two MS/MS transitions and its ion ratios, according
to Decision 2002/657/EC. The validated method was applied to wastewater treatment
plant samples, assessing the concentration of micropollutants after secondary
biological and tertiary UV treatments. Lab-scale photolysis and ozonation
experiments were also performed with the secondary effluents, with ozonation
showing the best performance for the removal of most of the determined
micropollutants.
PMID- 26431861
TI - Primary care and cancer: integration is key.
PMID- 26431862
TI - Primary care in cancer control: towards mature cancer care.
PMID- 26431863
TI - Chinese perspective of the role of primary care in cancer control.
PMID- 26431864
TI - Paying for the expanding role of primary care in cancer control.
PMID- 26431865
TI - Referral of suspected cancers: the NICE approach.
PMID- 26431866
TI - The expanding role of primary care in cancer control.
AB - The nature of cancer control is changing, with an increasing emphasis, fuelled by
public and political demand, on prevention, early diagnosis, and patient
experience during and after treatment. At the same time, primary care is
increasingly promoted, by governments and health funders worldwide, as the
preferred setting for most health care for reasons of increasing need, to
stabilise health-care costs, and to accommodate patient preference for care close
to home. It is timely, then, to consider how this expanding role for primary care
can work for cancer control, which has long been dominated by highly technical
interventions centred on treatment, and in which the contribution of primary care
has been largely perceived as marginal. In this Commission, expert opinion from
primary care and public health professionals with academic and clinical cancer
expertise-from epidemiologists, psychologists, policy makers, and cancer
specialists-has contributed to a detailed consideration of the evidence for
cancer control provided in primary care and community care settings. Ranging from
primary prevention to end-of-life care, the scope for new models of care is
explored, and the actions needed to effect change are outlined. The strengths of
primary care-its continuous, coordinated, and comprehensive care for individuals
and families-are particularly evident in prevention and diagnosis, in shared
follow-up and survivorship care, and in end-of-life care. A strong theme of
integration of care runs throughout, and its elements (clinical, vertical, and
functional) and the tools needed for integrated working are described in detail.
All of this change, as it evolves, will need to be underpinned by new research
and by continuing and shared multiprofessional development.
PMID- 26431867
TI - Intranasal exposure to silica nanoparticles induces alterations in pro
inflammatory environment of rat brain.
AB - Silica nanoparticles (SiNPs) are being used increasingly in biomedical and
industrial fields; however, their adverse effects on human health have not been
fully investigated. In this study, we focused on some of the toxicological
aspects of SiNPs by studying oxidative stress and pro-inflammatory responses in
the frontal cortex, corpus striatum and hippocampus regions of rat brain. Wistar
rats were exposed to SiNPs of size 80 nm and 10 nm at a dose of 150 ug/50 uL
phosphate-buffered saline/rat for 30 days. The results indicated a significant
increase of lipid peroxide levels and hydrogen peroxide content in various
regions of the treated rat brain. Moreover, these changes were accompanied with a
significant decrease in the activities of manganese superoxide dismutase,
glutathione reductase, catalase and reduced glutathione in different brain
regions, suggesting impaired antioxidant defence system. Furthermore, SiNPs
exposure not only increased messenger RNA (mRNA) and protein expression of
nuclear factor-kappaB (NF-kappaB) but also significantly increased the mRNA and
protein levels of tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL
1beta) and monocyte chemoattractant protein 1 (MCP-1) in different regions of rat
brain. Cumulatively, these data suggest that SiNPs induced the activation of NF
kappaB and increased the expression of TNF-alpha, IL-1beta and MCP-1 in rat
brain, possibly via redox-sensitive cellular signalling pathways.
PMID- 26431868
TI - The Sixth International Water and Health Seminar, Cannes, France, June 16-18,
2014.
PMID- 26431869
TI - Reducing pathogens in combined sewer overflows using ozonation or UV irradiation.
AB - Fecal contamination of water resources is a major public health concern in
densely populated areas since these water bodies are used for drinking water
production or recreational purposes. A main source of this contamination
originates from combined sewer overflows (CSOs) in regions with combined sewer
systems. Thus, the treatment of CSO discharges is urgent. In this study, we
explored whether ozonation or UV irradiation can efficiently reduce pathogenic
bacteria, viruses, and protozoan parasites in CSOs. Experiments were carried out
in parallel settings at the outflow of a stormwater settling tank in the Ruhr
area, Germany. The results showed that both techniques reduce most hygienically
relevant bacteria, parasites and viruses. Under the conditions tested, ozonation
yielded lower outflow values for the majority of the tested parameters.
PMID- 26431870
TI - Characterization of modified proteins in plasma from a subtype of schizophrenia
based on carbonyl stress: Protein carbonyl is a possible biomarker of psychiatric
disorders.
AB - Although it's well known that protein carbonyl (PCO) and advanced glycation end
products (AGEs) levels are elevated in plasma from patients with renal
dysfunction, we recently identified patients who had no renal dysfunction but
possessed high levels of plasma pentosidine (PEN), which is an AGEs, and low
vitamin B6 levels in serum. In this study, we investigated the status of carbonyl
stress to characterize the subtype of schizophrenia. When plasma samples were
subjected to Western blot analysis for various AGEs, clear differences were only
observed with the anti-PEN antibody in the plasma from schizophrenic patients.
Moreover, we determined the formation of protein carbonyl (PCO), a typical
indicator of carbonyl stress, occurred prior to the accumulation of PEN in the
plasma of schizophrenic patients. PCO levels in the plasma from schizophrenic
patients were significantly higher than that from healthy subjects. Western blots
analysis clearly showed that albumin and IgG were markedly carbonylated in the
plasma of some patients. Thus, PCOs may be a novel marker of carbonyl stress-type
schizophrenia in addition to albumin containing PEN structure.
PMID- 26431871
TI - Selective enhancement of wnt4 expression by cyclic AMP-associated cooperation
between rat central astrocytes and microglia.
AB - The wnt protein family has important members involved in cell differentiation,
proliferation and plasticity expression; however, little is known about its
biosynthesis processes. On the other hand, an increase in the intracerebral
cyclic adenosine 3', 5'-monophosphate (cAMP) level leads to synaptic plasticity
via the de novo synthesis of any protein. Here, the effect of dibutyryl cAMP
(dbcAMP), a membrane permeability cAMP analog, on the wnt family was investigated
in rat primary-cultured glial cells containing astrocytes and microglia. Among
wnt3a, 4, 5a, 7a and 11 mRNA, only wnt4 expression was increased by longer
treatment (24 h), compared with short treatment (2 h), with dbcAMP in a
concentration-dependent manner, and its effect reached statistical significance
at 1 mM. In cultures of isolated astrocytes or microglia, wnt4 expression was not
affected by 1 mM dbcAMP for 24 h, and microglial wnt4 protein was undetectable
even when cells were treated with the drug. Mixed glial cells treated for 24 h
with 1 mM dbcAMP showed significantly increased wnt4 protein, as well as mRNA.
Immunofluorescence manifested that cells that expressed wnt4 protein were
astrocytes, but not microglia. Intraperitoneal injection of 1.25 mg/kg rolipram,
a phosphodiesterase (PDE) IV inhibitor that can pass through the blood brain
barrier and inhibits cAMP degradation specifically, showed a tendency to increase
wnt4 expression in the adult rat brain after 24 h, and the increases in wnt4 mRNA
and protein levels reached statistical significance in the hippocampus and
striatum, respectively. This is the first finding to help elucidate the selective
biosynthesis of central wnt4 through cAMP-stimulated microglia and astrocytes
interaction.
PMID- 26431872
TI - Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A
potential therapeutic strategy against oxidative stress-induced cell death.
AB - The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has
multiple functions, including mediating oxidative stress-induced neuronal cell
death. This process is associated with disulfide-bonded GAPDH aggregation. Some
reports suggest a link between GAPDH and the pathogenesis of several oxidative
stress-related diseases. However, the pathological significance of GAPDH
aggregation in disease pathogenesis remains unclear due to the lack of an
effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH
aggregation inhibitor (GAI) peptide and evaluated its biological profile. The
decapeptide GAI specifically inhibited GAPDH aggregation in a concentration
dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic
activity or cell viability. The GAI peptide also exerted a protective effect
against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could
potentially serve as a tool to investigate GAPDH aggregation-related
neurodegenerative and neuropsychiatric disorders and as a possible therapy for
diseases associated with oxidative stress-induced cell death.
PMID- 26431873
TI - Ubiquitous versus restricted expression of the two mouse dendritic cell C-type
lectin receptors, DCIR1 and DCAR2, among myeloid cells.
AB - Dendritic cell inhibitory receptor 1 (DCIR1, also known as DCIR and Clec4a2) and
dendritic cell activating receptor 2 (DCAR2, also known as DCAR and Clec4b1) are
mouse lectin receptors expressed on antigen presenting cells. They have
structurally similar C-type lectin domains, of which amino acid sequences show
90.5% identity, and commercially available antibodies against them cross-react
each other. Here we have established novel antibodies against DCIR1 and DCAR2
that can unambiguously discriminate DCIR1 and DCAR2 and examined their
distribution among various immune cells. While DCIR1 was ubiquitously expressed
on myeloid cells, including conventional DCs (cDCs), macrophages, neutrophils and
eosinophils, in various immune organs, significant expression of DCAR2 was
detected only on subpopulations of cDCs from bone marrow and skin-draining lymph
nodes. Interestingly, in FITC-painted mice, DCAR2 was expressed on all of the
FITC(+) cDCs, which had migrated from the skin after FITC painting, suggesting
that DCAR2 can be a marker of migratory cDCs in skin-draining lymph nodes. Our
findings provide a basis to investigate in vivo function of DCIR1 and DCAR2.
PMID- 26431874
TI - KDM3A interacted with p53K372me1 and regulated p53 binding to PUMA in gastric
cancer.
AB - Chemoresistance remains a major problem in the treatment of gastric cancer
patients, leading to the serious limitation of efficacy of chemotherapeutic
regime. However, the underlying mechanism remains largely unknown. In our present
study, we for the first time found that knock down of KDM3A can promote apoptosis
induced by chemoreagent Cisplatin and Paclitaxel through p53. Mechanistically,
through promoting p53 binding to the promoter of PUMA. However, knock down of
KDM3A as such doesn't affect p53 level. In addition, KDM3A can interact with
p53K372me1 in protein-protein interaction fashion, leading to the inactivation of
p53, may eventually leading to chemoresistance of gastric cancer.
PMID- 26431875
TI - Intracellular Ca(2+) oscillations generated via the extracellular Ca(2+)-sensing
receptor (CaSR) in response to extracellular Ca(2+) or L-phenylalanine: Impact of
the highly conservative mutation Ser170Thr.
AB - The extracellular Ca(2+)-sensing receptor (CaSR) is an allosteric protein that
responds to changes in the extracellular concentration of Ca(2+) ([Ca(2+)]e) and
aromatic amino acids with the production of different patterns of oscillations in
intracellular Ca(2+) concentration ([Ca(2+)]i). An increase in [Ca(2+)]e
stimulates sinusoidal oscillations in [Ca(2+)]i whereas aromatic amino acid
induced CaR activation in the presence of a threshold [Ca(2+)]e promotes
transient oscillations in [Ca(2+)]i. Here, we examined spontaneous and ligand
evoked [Ca(2+)]i oscillations in single HEK-293 cells transfected with the wild
type CaSR or with a mutant CaSR in which Ser170 was converted to Thr (CaSRS170T).
Our analysis demonstrates that cells expressing CaSRS170T display [Ca(2+)]i
oscillations in the presence of low concentrations of extracellular Ca(2+) and
respond to L-Phe with robust transient [Ca(2+)]i oscillations. Our results
indicate that the S170T mutation induces a marked increase in CaSR sensitivity to
[Ca(2+)]e and imply that the allosteric regulation of the CaSR by aromatic amino
acids is not only mediated by an heterotropic positive effect on Ca(2+) binding
cooperativity but, as biased agonists, aromatic amino acids stabilize a CaSR
conformation that couples to a different signaling pathway leading to transient
[Ca(2+)]i oscillations.
PMID- 26431877
TI - Urotensin II contributes to collagen synthesis and up-regulates Egr-1 expression
in cultured pulmonary arterial smooth muscle cells through the ERK1/2 pathway.
AB - AIM: The objective of this study was to investigate the effects of urotensin II
(UII) treatment on the proliferation and collagen synthesis of cultured rat
pulmonary arterial smooth muscle cells (PASMCs) and to explore whether these
effects are mediated by mitogen-activated protein kinase (MAPK) signaling
pathways and early growth response 1 (Egr-1). METHODS: The proliferation of
cultured PASMCs stimulated with different doses of UII was detected by BrdU
incorporation. The mRNA expression levels of procollagen I (procol I),
procollagen III (procol III), extracellular regulated protein kinase 1/2
(ERK1/2), stress-stimulated protein kinase (Sapk), p38 MAPK (p38), and Egr-1 mRNA
in cultured PASMCs after treatment with UII, the UII-specific antagonist
urantide, and the ERK1/2 inhibitor PD98059 were detected by real-time polymerase
chain reaction (PCR), and the protein expression levels of procol I, procol III,
phosphorylated (p)-ERK1/2, p-Sapk, p-p38, and Egr-1 were detected by Western
blotting. RESULTS: Treatment with UII increased the proliferation of cultured
PASMCs in a dose-dependent manner (P<0.05). However, treatment with urantide and
PD98059 inhibited the promoting effect of UII on PASMC proliferation (P<0.05).
Real-time PCR analysis showed that UII up-regulated the expression of procol I,
procol III, ERK1/2, Sapk, and Egr-1 mRNA (P<0.05), but not p38 mRNA. However, the
up-regulating effect of UII was inhibited by PD98059 and urantide. Western
blotting analysis showed that UII increased the synthesis of collagen I, collagen
III, p-ERK1/2, p-Sapk, and Egr-1, and these effects also were inhibited by
PD98059 and urantide (P<0.05). CONCLUSIONS: Egr-1 participates in the UII
mediated proliferation and collagen synthesis of cultured rat PASMCs via
activation of the ERK1/2 signaling pathway.
PMID- 26431876
TI - Hepatic scavenger receptor BI is associated with type 2 diabetes but unrelated to
human and murine non-alcoholic fatty liver disease.
AB - Scavenger receptor, class B type I (SR-BI) is a physiologically relevant
regulator of high density lipoprotein (HDL) metabolism. Low HDL is a common
feature of patients with non-alcoholic fatty liver disease (NAFLD). Here, hepatic
SR-BI expression was analyzed in human and murine NAFLD. In primary human
hepatocytes NAFLD relevant factors like inflammatory cytokines,
lipopolysaccharide and TGF-beta did not affect SR-BI protein. Similarly, oleate
and palmitate had no effect. The adipokines chemerin, adiponectin, leptin and
omentin did not regulate SR-BI expression. Accordingly, hepatic SR-BI was not
changed in human and murine fatty liver and non-alcoholic steatohepatits. SR-BI
was higher in type 2 diabetes patients but not in those with
hypercholesterolemia. The current study indicates a minor if any role of SR-BI in
human and murine NAFLD.
PMID- 26431879
TI - O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates
their transcriptional activities.
AB - The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine
modifies a myriad of proteins and regulates their function, stability and
localization. O-GlcNAc modification is common among chromosome-associated
proteins, such as transcription factors, suggesting its extensive involvement in
gene expression regulation. In this study, we demonstrate the O-GlcNAc status of
the Sp family members of transcription factors and the functional impact on their
transcriptional activities. We highlight the presence of O-GlcNAc residues in Sp3
and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive
protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co
expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O
GlcNAc-specific antibody. Deletion mutants of Sp3 and Sp4 indicate that the
majority of O-GlcNAc sites reside in their N-terminal transactivation domain.
Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a
functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription
factors. Thereby, our study strengthens the current notion that O-GlcNAc
modification is an important regulator of protein interactome.
PMID- 26431878
TI - Angelica sinensis polysaccharides promotes apoptosis in human breast cancer cells
via CREB-regulated caspase-3 activation.
AB - Angelica sinensis polysaccharide (ASP) is purified from the fresh roots of
Angelica sinensis (AS). This traditional Chinese medicine has been used for
thousands of years for treating gynecological diseases and used in functional
foods for the prevention and treatment of various diseases, such as inflammation
and cancer. The antitumor activity of ASP is related to its biological
activities, because it suppresses a variety of pro-proliferative or anti
apoptotic factors that are dramatically expressed in cancer cells of given types.
In this study, we show that angelica sinensis polysaccharide induced apoptosis in
breast cancer cells of T47D over-expressing the Cyclic AMP response element
binding protein (CREB), inducing apoptosis-related signaling pathway activity.
The result also found that ASP caused cell death was linked to caspase activity,
accompanied by the loss of mitochondrial membrane potential, cytochrome c
release, and Bax translocation from the cytosol to the mitochondria. We found
that ASP significantly affected the poly-ADP-ribose polymerase (PARP), Bcl-2
Associated X Protein (Bax), Bcl-2, Bcl-xL and apoptotic protease activating
facter-1 (Apaf1) protein expression in a dose- and time-dependent manner. DAPI
staining and Flow cytometry were used to analyze apoptosis. The nude mice
xenograft model was used to evaluate the antitumor effect of ASP in vivo. ASP has
profound antitumor effect on T47D cells, probably by inducing apoptosis through
CREB signaling pathway. Thus, these results suggest that ASP would be a promising
therapeutic agent for breast cancer.
PMID- 26431880
TI - Smaller Amygdala Volumes in Patients With Chronic Low Back Pain Compared With
Healthy Control Individuals.
AB - Although preclinical and clinical data strongly support an association between
the amygdala and chronic pain by the presence of mood and cognitive disturbances
in affected individuals, little attention has been paid to morphometric
measurement of the structure in patients with chronic low back pain (CLBP). In
the present study, magnetic resonance volumetric and surface analysis, using
FMRIB's integrated registration and segmentation tool (FIRST), were performed to
compare structural magnetic resonance imaging data obtained from 33 patients with
CLBP with those obtained from 33 demographically similar healthy control
individuals. Our results indicated that the normalized volumes of the left and
right amygdala were significantly smaller in the CLBP group than in the control
group. Detailed surface analyses further localized these differences. The degree
of volume reduction was different between the left and right amygdala, with a
greater involvement of the left side. Both groups exhibited similar significant
hemispheric asymmetry for the amygdala (left > right). Similar asymmetry was
suggested in the subgroup of 24 unmedicated patients. No significant correlations
were found between amygdala volumes and pain characteristics or depressive
symptoms. Our study provides in vivo imaging evidence of abnormal morphology of
the amygdala in patients with CLBP using a fully automated segmentation method.
PERSPECTIVE: Our study found that patients with CLBP had statistically
significantly smaller normalized volumes of the bilateral amygdala, compared with
healthy control individuals, with a greater involvement of the left side. These
results may help to characterize the impaired affective-cognitive dimension in
patients with chronic pain.
PMID- 26431881
TI - My Brain Reads Pain in Your Face, Before Knowing Your Gender.
AB - Humans are expert at recognizing facial features whether they are variable
(emotions) or unchangeable (gender). Because of its huge communicative value,
pain might be detected faster in faces than unchangeable features. Based on this
assumption, we aimed to find a presentation time that enables subliminal
discrimination of pain facial expression without permitting gender
discrimination. For 80 individuals, we compared the time needed (50, 100, 150, or
200 milliseconds) to discriminate masked static pain faces among anger and
neutral faces with the time needed to discriminate male from female faces.
Whether these discriminations were associated with conscious reportability was
tested with confidence measures on 40 other individuals. The results showed that,
at 100 milliseconds, 75% of participants discriminated pain above chance level,
whereas only 20% of participants discriminated the gender. Moreover, this pain
discrimination appeared to be subliminal. This priority of pain over gender might
exist because, even if pain faces are complex stimuli encoding both the sensory
and the affective component of pain, they signal a danger. This supports the
evolution theory relating to the necessity of quickly reading aversive emotions
to ensure survival but might also be at the basis of altruistic behavior such as
help and compassion. PERSPECTIVE: This study shows that pain facial expression
can be processed subliminally after brief presentation times, which might be
helpful for critical emergency situations in clinical settings.
PMID- 26431882
TI - Concordance of Phantom and Residual Limb Pain Phenotypes in Double Amputees:
Evidence for the Contribution of Distinct and Common Individual Factors.
AB - Most, but not all, limb amputees develop phantom limb pain (PLP) or residual limb
pain (RLP), and large interindividual differences in pain intensity and course
are apparent. The present cross-sectional study of 122 double amputees
investigated the possible role of genetic factors in PLP and RLP, assuming that
strong individual predisposition results in high intraindividual concordance in
pain phenotype. Intraindividual concordance was observed in 116 (95%) patients
for development of PLP and in 110 patients (90%) for development of RLP. For both
pain types, high intraindividual concordance was also observed for remission and
current intensity. Moderate association for lifetime history and current
intensity of PLP and RLP was observed both within and between limbs. The high
intraindividual concordance in pain phenotypes suggests strong individual
predisposition for PLP and RLP development. However, the finding of only moderate
association between PLP and RLP suggests that susceptibility to these pain
phenomena involves distinct, as well as common, risk factors. Genome-wide studies
in large samples of single amputees may facilitate the dissection of these
phenotypes and their underlying mechanisms. PERSPECTIVE: The observation of high
intraindividual concordance for PLP and RLP in 122 double amputees suggests that
individual factors contribute to post-amputation pain. The relatively low
intraindividual association between PLP and RLP suggests that these factors are
at least partially specific for each pain type.
PMID- 26431883
TI - Associations of birth outcomes with maternal polybrominated diphenyl ethers and
thyroid hormones during pregnancy.
AB - BACKGROUND: Previous research has linked polybrominated diphenyl ether (PBDE)
exposure to poor birth outcomes and altered thyroid hormone levels. OBJECTIVES:
We examined whether maternal PBDE serum levels were associated with infant birth
weight (g), head circumference (cm), birth length (cm), and birth weight
percentile for gestational age. We explored the potential for a mediating role of
thyroid hormone levels. METHODS: During 2008-2010, we recruited 140 pregnant
women in their third trimester as part of a larger clinical obstetrics study
known as Healthy Pregnancy, Healthy Baby. Blood samples were collected during a
routine prenatal clinic visit. Serum was analyzed for PBDEs, phenolic
metabolites, and thyroid hormones. Birth outcome information was abstracted from
medical records. RESULTS: In unadjusted models, a two-fold increase in maternal
BDE 153 was associated with an average decrease in head circumference of 0.32cm
(95% CI: -0.53, -0.12); however, this association was attenuated after control
for maternal risk factors. BDE 47 and 99 were similarly negatively associated but
with 95% confidence intervals crossing the null. Associations were unchanged in
the presence of thyroid hormones. CONCLUSIONS: Our data suggest a potential
deleterious association between maternal PBDE levels and infant head
circumference; however, confirmatory studies are needed in larger sample sizes. A
mediating role of thyroid hormones was not apparent.
PMID- 26431884
TI - Morphology and molecular phylogeny of Pleuronema orientale spec. nov. and
Pleuronema paucisaetosum spec. nov. (Ciliophora, Scuticociliata) from Hangzhou
Bay, China.
AB - Two novel species, Pleuronema orientale spec. nov. and Pleuronema paucisaetosum
spec. nov., isolated from coastal waters of Hangzhou Bay, China, were
investigated with standard methods. Pleuronema orientale is characterized as
follows: size in vivo 95-135 * 50-85 MUm; usually one spherical macronucleus; 12
15 prolonged caudal cilia; two or three preoral kineties and 42-50 somatic
kineties; membranelle 1 (M1) about 20 % of the anterior fragment of membranelle 2
(M2a) in length, consisting of three longitudinal rows of kinetosomes; posterior
end of M2a hook-like; membranelle 3 (M3) three-rowed. Pleuronema paucisaetosum is
characterized as follows: size in vivo about 55-85 * 25-55 MUm; four or five
preoral kineties and 21-23 somatic kineties; posterior end of M2a hook-like; M3
three-rowed. The small-subunit rRNA gene was sequenced for both species.
Phylogenetic analyses revealed that P. orientale is most closely related to
Pleuronema puytoraci and that P. paucisaetosum is sister to Pleuronema grolierei
and Pleuronema setigerum (GenBank accession no. JX310015). With the inclusion of
the two new sequences, the monophyly of the genus Pleuronema is not supported.
PMID- 26431886
TI - Promoting protein self-association in non-glycosylated Thermomyces lanuginosus
lipase based on crystal lattice contacts.
AB - We have used the crystal structure of Thermomyces lanuginosus lipase (TlL) to
identify and strengthen potential protein-protein interaction sites in solution.
As wildtype we used a deglycosylated mutant of TlL (N33Q). We designed a number
of TlL mutants to promote interactions via interfaces detected in the crystal
lattice structure, through strengthening of hydrophobic, polar or electrostatic
contacts or truncation of sterically blocking residues. We identify a mutant
predicted to lead to increased interfacial hydrophobic contacts (N92F) that shows
markedly increased self-association properties on native gradient gels. While
wildtype TlL mainly forms monomer and <5% dimers, N92F forms stable trimers and
dimers according to Size-Exclusion Chromatography and Small-Angle X-ray
Scattering. These oligomers account for ~25% of the population and their
enzymatic activity is comparable to that of the monomer. Self-association
stabilizes TlL against thermal denaturation. Furthermore, the trimer is stable to
dilution and requires high concentrations (>2M) of urea to dissociate. We
conclude that crystal lattice contacts are a good starting point for design
strategies to promote protein self-association.
PMID- 26431887
TI - Neoadjuvant Chemotherapy With Gemcitabine and Cisplatin for Plasmacytoid
Urothelial Bladder Cancer: A Case Report and Review of the Literature.
PMID- 26431885
TI - Bendavia restores mitochondrial energy metabolism gene expression and suppresses
cardiac fibrosis in the border zone of the infarcted heart.
AB - AIMS: We have observed that Bendavia, a mitochondrial-targeting peptide that
binds the phospholipid cardiolipin and stabilizes the components of electron
transport and ATP generation, improves cardiac function and prevents left
ventricular remodeling in a 6week rat myocardial infarction (MI) model. We
hypothesized that Bendavia restores mitochondrial biogenesis and gene expression,
suppresses cardiac fibrosis, and preserves sarco/endoplasmic reticulum (SERCA2a)
level in the noninfarcted border zone of infarcted hearts. MAIN METHODS: Starting
2h after left coronary artery ligation, rats were randomized to receive Bendavia
(3mg/kg/day), water or sham operation. At 6weeks, PCR array and qRT-PCR was
performed to detect gene expression. Picrosirius red staining was used to analyze
collagen deposition. KEY FINDINGS: There was decreased expression of 70 out of 84
genes related to mitochondrial energy metabolism in the border zone of untreated
hearts. This down-regulation was largely reversed by Bendavia treatment.
Downregulated mitochondrial biogenesis and glucose & fatty acid (FA) oxidation
related genes were restored by administration of Bendavia. Matrix
metalloproteinase (MMP9) and tissue inhibitor of metalloproteinase (TIMP1) gene
expression were significantly increased in the border zone of untreated hearts.
Bendavia completely prevented up-regulation of MMP9, but maintained TIMP1 gene
expression. Picrosirius red staining demonstrated that Bendavia suppressed
collagen deposition within border zone. In addition, Bendavia showed a trend
toward restoring SERCA2a expression. SIGNIFICANCE: Bendavia restored expression
of mitochondrial energy metabolism related genes, prevented myocardial matrix
remodeling and preserved SERCA2a expression in the noninfarcted border, which may
have contributed to the preservation of cardiac structure and function.
PMID- 26431888
TI - Elevated IL-35 in bone marrow of the patients with acute myeloid leukemia.
AB - Acute myeloid leukemia (AML) is the most common hematological malignancy in
adults, but the etiology of it remains poorly understood. IL-35 is a recently
described cytokine composed of an IL-12 subunit p35 and an IL-27 subunit Epstein
Barr virus induced gene 3 (EBI3), and has an immunosuppressive effect on
inflammation through induction of regulatory T cells (Tregs) and suppression of
Th1 and Th17. Recently, we have illustrated that concentrations of IL-35 in
peripheral blood are up-regulated in newly diagnosed (ND) AML patients. However,
whether IL-35 in bone marrow is increased in AML patients is not clear. In this
study, we examined IL-35 in bone marrow by various methods including RT-PCR,
ELISA, FCM and IHC, and found that IL-35 levels are also increased significantly
in bone marrow of adult AML patients. Furthermore, we investigated that
concentrations of bone marrow IL-35 in ND group were higher than that in complete
remission (CR) group and control group, but there was no significant difference
compared to that in relapse group. In conclusion, IL-35 was elevated in bone
marrow of adult AML patients and this increase was correlated with the clinical
stages of malignancy, suggesting that IL-35 is involved in pathogenesis of AML.
PMID- 26431889
TI - HLA-frequencies of Austrian umbilical cord blood samples.
AB - We investigated HLA-A, HLA-B, and HLA-DRB1 gene frequencies in 1368 unrelated
Austrian umbilical cord blood samples. HLA-C gene frequencies were investigated
in a subgroup of 503 samples. HLA typing was performed via sequenced-based typing
(SBT). The aim of this study was to examine the HLA diversity in a large Austrian
population sample. In addition we present results of a subsample of 100 samples
at a subtype level. This study is the first systematic investigation of donated
umbilical cord blood samples in the Austrian population.
PMID- 26431890
TI - Identification and localization of a Novel Invasin of Plasmodium falciparum.
AB - Plasmodium falciparum is the causative organism for the most severe form of
malaria among humans. The clinical symptoms are accredited to the asexual stage
of parasite life cycle, involving merozoite invasion of erythrocyte, development
and re-invasion into the new erythrocyte. Interaction of parasite proteins
present on the surface or secreted from apical organelles with the host receptors
is indispensable for the invasion process. Identification and elucidation of
precise localization and function of these proteins will not only enhance our
understanding of this process but will also aid in the progress of development of
treatment strategies against malaria. Here we report the identification and
localization of a novel protein, PfAEP (P. falciparum Apical Exonemal Protein)
(PF3D7_1137200/ PF11_0383) which is conserved across Plasmodium species.
Transcription and translation analysis have confirmed its expression in the
schizont stage of P. falciparum. Super-resolution microscopy in schizonts and
merozoites revealed its localization in the exonemes of P. falciparum.
PMID- 26431891
TI - Renal Collision and Composite Tumors: Imaging and Pathophysiology.
AB - OBJECTIVE: To illustrate the imaging appearances of a spectrum of renal collision
and composite tumors. Occurrence of collision and composite tumors in the
genitourinary tract is rare compared to the usual occurrence of synchronous
tumors. METHODS: Case studies were chosen that represent the different tumors.
Analysis was made on both the imaging and the pathology if excision was
performed. RESULTS: Presence of 2 different cell types can lead to confusing
imaging findings, and biopsy or excision is typically needed for final diagnosis.
Some composite tumors have a characteristic appearance on imaging based on their
pathologic features. CONCLUSION: Familiarity with imaging findings may help
radiologists include these tumors in their differential diagnosis.
PMID- 26431892
TI - Prevention of Ischemic Priapism in Sickle Cell Disease: Sildenafil: Commentary
on: Randomized Controlled Trial of Sildenafil for Preventing Recurrent Ischemic
Priapism in Sickle Cell Disease.
PMID- 26431893
TI - Colocalization properties of elementary Ca(2+) release signals with structures
specific to the contractile filaments and the tubular system of intact mouse
skeletal muscle fibers.
AB - Ca(2+) regulates several important intracellular processes. We combined second
harmonic generation (SHG) and two photon excited fluorescence microscopy (2PFM)
to simultaneously record the SHG signal of the myosin filaments and localized
elementary Ca(2+) release signals (LCSs). We found LCSs associated with Y-shaped
structures of the myosin filament pattern (YMs), so called verniers, in intact
mouse skeletal muscle fibers under hypertonic treatment. Ion channels crucial for
the Ca(2+) regulation are located in the tubular system, a system that is
important for Ca(2+) regulation and excitation-contraction coupling. We
investigated the tubular system of intact, living mouse skeletal muscle fibers
using 2PFM and the fluorescent Ca(2+) indicator Fluo-4 dissolved in the external
solution or the membrane dye di-8-ANEPPS. We simultaneously measured the SHG
signal from the myosin filaments of the skeletal muscle fibers. We found that at
least a subset of the YMs observed in SHG images are closely juxtaposed with Y
shaped structures of the transverse tubules (YTs). The distances of corresponding
YMs and YTs yield values between 1.3 MUm and 4.1 MUm including pixel uncertainty
with a mean distance of 2.52+/-0.10 MUm (S.E.M., n=41). Additionally, we observed
that some of the linear-shaped areas in the tubular system are colocalized with
linear-shaped areas in the SHG images.
PMID- 26431894
TI - Protein domain mapping by internal labeling and single particle electron
microscopy.
AB - In recent years, electron microscopy (EM) and single particle analysis have
emerged as essential tools for investigating the architecture of large biological
complexes. When high resolution is achievable, crystal structure docking and de
novo modeling allows for precise assignment of individual protein domain
sequences. However, the achievable resolution may limit the ability to do so,
especially when small or flexible complexes are under study. In such cases,
protein labeling has emerged as an important complementary tool to characterize
domain architecture and elucidate functional mechanistic details. All labeling
strategies proposed to date are either focused on the identification of the
position of protein termini or require multi-step labeling strategies,
potentially interfering with the final labeling efficiency. Here we describe a
strategy for determining the position of internal protein domains within EM maps
using a recombinant one-step labeling approach named Efficient Mapping by
Internal Labeling (EMIL). EMIL takes advantage of the close spatial proximity of
the GFP's N- and C-termini to generate protein chimeras containing an internal
GFP at desired locations along the main protein chain. We apply this method to
characterize the subunit domain localization of the human Polycomb Repressive
Complex 2.
PMID- 26431895
TI - FEI's direct electron detector developments: Embarking on a revolution in cryo
TEM.
AB - In early 2011 FEI Company launched the "Falcon", its first commercial direct
electron detector product intended for application in 3-D electron microscopy in
the life sciences. In this paper we discuss the principle of direct electron
detection and its implementation in Falcon cameras. We describe the signal
formation in the sensor and its impact on the detection quantum efficiency (DQE)
of the sensor. Insights into the signal formation led us to improved camera
designs. Three significant improvements are discussed. (1) Back thinning of the
sensor. This is implemented in the second-generation Falcon (Falcon 2), where the
sensor thickness is reduced to 50 MUm, and in the latest generation Falcon 3
detector with further back-thinning down to 30 MUm. (2) The introduction of
electron counting, a signal processing technology implemented in Falcon 3. (3)
Dose fractionation mode, which allows the user to access intermediate results
during the illumination of the sample.
PMID- 26431896
TI - Mineral-bearing vesicle transport in sea urchin embryos.
AB - Sea urchin embryos sequester calcium from the sea water. This calcium is
deposited in a concentrated form in granule bearing vesicles both in the
epithelium and in mesenchymal cells. Here we use in vivo calcein labeling and
confocal Raman spectroscopy, as well as cryo-FIB-SEM 3D structural
reconstructions, to investigate the processes occurring in the internal cavity of
the embryo, the blastocoel. We demonstrate that calcein stained granules are also
present in the filopodial network within the blastocoel. Simultaneous
fluorescence imaging and Raman spectroscopy show that these granules do contain a
calcium mineral. By tracking the movements of these granules, we show that the
granules in the epithelium and primary mesenchymal cells barely move, but those
in the filopodial network move long distances. We could however not detect any
unidirectional movement of the filopodial granules. We also show the presence of
mineral containing multivesicular vesicles that also move in the filopodial
network. We conclude that the filopodial network is an integral part of the
mineral transport process, and possibly also for sequestering calcium and other
ions. Although much of the sequestered calcium is deposited in the mineralized
skeleton, a significant amount is used for other purposes, and this may be
temporarily stored in these membrane-delineated intracellular deposits.
PMID- 26431897
TI - Functional Mapping in Pediatric Epilepsy Surgical Candidates: Functional Magnetic
Resonance Imaging Under Sedation With Chloral Hydrate.
AB - OBJECTIVES: Functional magnetic resonance imaging is a useful tool to lateralize
and localize language in presurgical patients, as well as to localize other
functionally salient cortex. The procedure is typically reserved for older
children and adults, since it necessitates cooperation and participation in
tasks. We have explored the applicability of functional magnetic resonance
imaging for language and motor mapping at our epilepsy surgical center in younger
children under sedation with chloral hydrate. METHODS: A series of 24 consecutive
patients undergoing magnetic resonance imaging, between ages 16 months and 11
years, were scanned under sedation. Assisted finger-tapping and foot-tapping
tasks were conducted for the purpose of motor mapping in nine patients, and a
speech-based auditory task was conducted in 23 of the 24 patients for the purpose
of lateralizing and localizing language. RESULTS: Significant blood oxygen level
dependent signal increases in hand and foot regions of the primary motor cortex
were generated in all but one patient who underwent the motor mapping tasks.
Signal increases in receptive language cortex were convincingly generated in 12
of the 23 (52%) patients who underwent the speech-based auditory task.
CONCLUSIONS: These results suggest that functional magnetic resonance imaging can
help to localize motor and/or somatosensory cortex and language cortex in young
children under sedation with chloral hydrate. This procedure may be used to
assist in presurgical planning. The findings also imply that a sedating agent may
be used in pediatric neuroimaging as an alternative to general anesthesia.
PMID- 26431899
TI - Microalgae-microbial fuel cell: A mini review.
AB - Microalgae-microbial fuel cells (mMFCs) are a device that can convert solar
energy to electrical energy via biological pathways. This mini-review lists new
research and development works on microalgae processes, microbial fuel cell (MFC)
processes, and their combined version, mMFC. The substantial improvement and
technological advancement are highlighted, with a discussion on the challenges
and prospects for possible commercialization of mMFC technologies.
PMID- 26431898
TI - Encephalitis Lethargica With Isolated Substantia Nigra Lesions Followed by a
Second Encephalitis in a Child With Humoral Immunodeficiency.
AB - BACKGROUND: Encephalitis lethargica is an encephalitic illness with multiple
nervous system symptoms. Lesions only involving substantia nigra on magnetic
resonance imaging are uncommon, especially in children. A second encephalitis
illness after encephalitis lethargica has never been reported before. PATIENT
DESCRIPTION: We describe a 7-year-old boy with humoral immunity deficiency who
developed encephalitis lethargica associated with bilateral substantia nigra
lesions on magnetic resonance imaging. After a nearly complete recovery, he
developed encephalitis once again. He was diagnosed with encephalitis lethargica
with somnolence, akinetic mutism, and ophthalmoplegia after intermittent fever.
Cerebrospinal fluid pleocytosis and positive oligoclonal bands were documented.
Symmetrical substantia nigra lesions on high-intensity magnetic resonance imaging
gradually evolved into a liquid signal. He had almost recovered when he developed
fatigue and hypersomnia and was diagnosed with encephalitis again, supported by
mild pleocytosis in cerebrospinal fluid and subcortical white matter lesions in
the frontal lobes. His symptoms resolved following administration of
corticosteroids and immunoglobulins. CONCLUSION: This is the first report of an
immune-deficient child to develop encephalitis lethargica with isolated
substantia nigra lesions on magnetic resonance imaging and a second encephalitis
illness after recovery from encephalitis lethargica.
PMID- 26431900
TI - Early postnatal handling and environmental enrichment improve the behavioral
responses of 17-month-old 3xTg-AD and non-transgenic mice in the Forced Swim Test
in a gender-dependent manner.
AB - Forced Swimming Test (FST) models behavioural despair in animals by loss of
motivation to respond or the refusal to escape. The present study was aimed at
characterizing genetic (genotype and gender) and environmental factors (age/stage
of disease and rearing conditions: C, standard; H, early postnatal handling; EE,
environmental enrichment consisting in physical exercise as well as social and
object enrichment) that may modulate the poor behavioural and cognitive
flexibility response we have recently described in 12-month-old male 3xTg-AD mice
in the FST. The comprehensive analysis of the ethogram shown in the FST
considered the intervals of the test (0-2 and 2-6min), all the elicited
behavioural responses (immobility, swimming and climbing) and their features
(total duration and frequency of episodes). The long persistence of behaviours
found in 17-month-old (late-stages of disease) 3xTg-AD mice was comparable to
that recently described in males at 12 months of age (beginning of advanced
stages) but also suggested increased age-dependent frailty in both genotypes. The
poor behavioral flexibility of 3xTg-AD mice to elicit the behavioural despair
shown by the NTg mice, was also found in the female gender. Finally, the present
work demonstrates that early-life interventions were able to improve the time and
frequency of episodes of immobility, being more evident in the female gender of
both old NTg and 3xTg-AD mice. Ontogenic modulation by early-postnatal handling
resulted in a more effective long-term improvement of the elicited behaviours in
the FST than that achieved by environmental enrichment. The results talk in favor
of the beneficence of early-life interventions on ageing in both healthy and
disease conditions.
PMID- 26431902
TI - From state dissociation to status dissociatus.
AB - The states of being are conventionally defined by the simultaneous occurrence of
behavioral, neurophysiological and autonomic descriptors. State dissociation
disorders are due to the intrusion of features typical of a different state into
an ongoing state. Disorders related to these conditions are classified according
to the ongoing main state and comprise: 1) Dissociation from prevailing
wakefulness as seen in hypnagogic or hypnopompic hallucinations, automatic
behaviors, sleep drunkenness, cataplexy and sleep paralysis 2) Dissociation from
rapid eye movement (REM) sleep as seen in REM sleep behavior disorder and lucid
dreaming and 3) Dissociation from NREM sleep as seen in the disorders of arousal.
The extreme expression of states dissociation is characterized by the
asynchronous occurrence of the various components of the different states that
prevents the recognition of any state of being. This condition has been named
status dissociatus. According to the underlying disorders/diseases and to their
severity, among status dissociatus we may recognize disorders in which such an
extreme dissociation occurs only at night time or intermittently (i.e.,
autoimmune encephalopathies, narcolepsy type 1 and IgLON5 parasomnia), and others
in which it occurs nearly continuously with complete loss of any conventionally
defined state of being, and of the circadian pattern (agrypnia excitata). Here,
we render a comprehensive review of all diseases/disorders associated with state
dissociation and status dissociatus and propose a critical classification of this
complex scenario.
PMID- 26431901
TI - Genetic polymorphisms in TNFSF13 and FDX1 are associated with IgA nephropathy in
the Han Chinese population.
AB - IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide,
and its pathogenesis is influenced by both genetic and environmental factors. In
this study, we evaluated 23 tag single-nucleotide polymorphisms (tSNPs) in 21
IgAN-associated genes, in 200 subjects with IgAN and 310 healthy gender- and age
matched unrelated control subjects with no history of renal disease or
hypertension. Using the co-dominant model, we found that two genotypes of
rs3803800 in TNFSF13 were associated with an increased risk of IgAN: "GA" (OR =
1.03, 95% CI = 0.71-1.51, p = 0.018) and "AA" (OR = 2.45, 95% CI = 1.29-4.65, p =
0.018). The "AA" genotype was also associated with an increased risk of IgAN in
the recessive model (OR = 2.41, 95% CI = 1.30-4.46, p = 0.018), as was the
genotype "AA" rs10488764 in FDX1 (OR = 1.88, 95% CI = 1.01-3.53, p = 0.048).
Interestingly, we found that the allele "A" of rs3803800 in TNFSF13 is associated
with a decreased risk of IgAN in females (OR = 0.43, 95% CI = 0.20-0.95, p =
0.009), but with an increased risk in males (OR = 1.78, 95% CI = 0.86-3.66, p =
0.009). Our findings, combined with previously reported results, suggest that
TNFSF13 and FDX1 have potential roles in IgAN in the Han Chinese population. This
information may be useful in the development of early prognostics for IgAN.
PMID- 26431903
TI - Maternal mortality among women with sickle-cell disease in France, 1996-2009.
AB - OBJECTIVE: To describe maternal mortality among women with sickle-cell disease in
France. STUDY DESIGN: Data from the national confidential enquiry into maternal
deaths and from reference centres for sickle-cell disease were examined to
identify women with this disease who died in France during 1996-2009. The
maternal mortality ratio among women with sickle-cell disease was estimated and
compared with the ratio in the general population. Characteristics of these women
and their pregnancies and circumstances of their deaths were examined in detail.
RESULTS: Fifteen maternal deaths occurred among an estimated 3300 live births to
women with sickle-cell disease, for a maternal mortality ratio of 454 per 100000
live births (95% CI [254; 750]), versus 9.4/100000 in the general population. Ten
women were homozygous (SS) for sickle-cell disease, and five were composite
heterozygotes. The episode leading to death appeared in the antepartum period for
seven women (47%). Two women died of septic shock during pregnancy, one at 6
weeks, the other at 24 weeks. The other 13 women (87%) died postpartum. Thirteen
deaths were directly attributable to sickle-cell disease. The other two maternal
deaths, both considered direct obstetric causes, were due to amniotic fluid
embolism and septic shock after post-amniocentesis chorioamnionitis. The expert
committee on maternal mortality judged seven of these 15 deaths (47%) to be
avoidable. CONCLUSION: Sickle-cell disease is responsible for a major excess risk
of maternal death in France, due mainly to direct complications of the disease.
PMID- 26431904
TI - Does short-term fasting promote pathological eating patterns?
AB - Fasting, or going a significant amount of time without eating, has been
identified as a risk factor for the development of pathological eating patterns.
Findings from several studies examining the impact of fasting on subsequent
eating behaviors have been mixed. The current study recruited college students to
record food intake, episodes of binge eating, and use of compensatory behaviors
before, throughout, and following a 24-hour fast. Participants attended an
initial appointment in which they completed measures of dietary restraint and
disinhibition and received instructions on self-monitoring and fasting.
Participants (N=122) self-monitored their eating behaviors for 96 h, including a
24-hour fasting period. Participants did not demonstrate significant increases in
disordered eating behaviors following the fast (e.g., objective binge episodes,
self-defined excessive eating or compensatory behavior use). Baseline
disinhibition predicted excessive eating as well as objective binge episodes both
before and after fasting. Altogether, findings have implications for research
seeking to further understand how fasting may contribute to the development of
pathological eating patterns; specifically, it seems that the ED risk associated
with fasting is derived from the behavior's interaction with other individual
difference variables.
PMID- 26431906
TI - Testing the antidepressant properties of the peptide ARA290 in a human
neuropsychological model of drug action.
AB - Studies on the neural effects of Erythropoietin (EPO) indicate that EPO may have
antidepressant effects. Due to its hematopoietic effects, EPO may cause serious
side-effects with repeated administration if patients are not monitored
extensively. ARA290 is an EPO-analog peptide without such hematopoietic side
effects but may have neurotrophic and antidepressant effects. The aim of this
study was to investigate the possible antidepressant effects of ARA290 in a
neuropsychological model of drug action. Healthy participants (N=36) received
ARA290 (2mg) or placebo in a double-blind, randomized, parallel-group design.
Neural and cognitive effects were assessed one week after administration. Primary
outcome measures were the neural processing of fearful vs happy faces and the
behavioral recognition of emotional facial expressions. ARA290-treated
individuals displayed lower neural responses to happy faces in the fusiform
gyrus. ARA290 tended to lower the recognition of happy and disgust facial
expressions. Although ARA290 was not associated with a better memory for positive
words, it was associated with faster categorization of positive vs negative
words. Finally, ARA290 increased attention towards positive emotional pictures.
No effects were observed on mood and affective symptoms. ARA290 may modulate some
aspects of emotional processing, however, the direction and the strength of its
effects do not unequivocally support an antidepressant-like profile for ARA290.
Future studies may investigate the effects of different timing and dose.
PMID- 26431905
TI - Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK
signaling.
AB - Fluoride is an effective caries prophylactic, but at high doses can also be an
environmental health hazard. Acute or chronic exposure to high fluoride doses can
result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis
is manifested as mottled, discolored, porous enamel that is susceptible to dental
caries. Fluoride induces cell stress, including endoplasmic reticulum stress and
oxidative stress, which leads to impairment of ameloblasts responsible for dental
enamel formation. Recently we reported that fluoride activates SIRT1 and
autophagy as an adaptive response to protect cells from stress. However, it still
remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this
study, we demonstrate that fluoride exposure generates reactive oxygen species
(ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy
induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the
mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial
damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP
synthesis, and H2AX phosphorylation (gammaH2AX), which is a marker of DNA damage.
We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK
inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased
fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC
decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II,
which resulted in an increase in the apoptosis mediators gammaH2AX and
cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1
phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS
mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or
125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8
oxoguanine, p-ATM, and gammaH2AX were increased compared to those in controls (0
ppm fluoride). These results suggest that fluoride-induced ROS generation causes
mitochondrial damage and DNA damage, which may lead to impairment of ameloblast
function. To counteract this impairment, SIRT1/autophagy is induced via JNK
signaling to protect cells/ameloblasts from fluoride-induced oxidative damage
that may cause dental fluorosis.
PMID- 26431907
TI - Rapid anti-depressant and anxiolytic actions following dopamine D1-D2 receptor
heteromer inactivation.
AB - A role for the mesolimbic dopaminergic system in the pathophysiology of
depression has become increasingly evident. Specifically, brain-derived
neurotrophic factor (BDNF) has been shown to be elevated in the nucleus accumbens
of depressed patients and to positively contribute to depression-like behaviour
in rodents. The dopamine D1-D2 receptor heteromer exhibits significant expression
in NAc and has also been shown to enhance BDNF expression and signalling in this
region. We therefore examined the effects of D1-D2 heteromer stimulation in rats
by SKF 83959, or its inactivation by a selective heteromer-disrupting TAT-D1
peptide on depression- and anxiety-like behaviours in non-stressed animals and in
animals exposed to chronic unpredictable stress. SKF 83959 treatment
significantly enhanced the latency to immobility in the forced swim test,
increased the latency to drink condensed milk and reduced total milk consumption
in the novelty-induced hypophagia test, and additionally reduced the total time
spent in the open arms in the elevated plus maze test. These pro-depressant and
anxiogenic effects of SKF 83959 were consistently abolished or attenuated by TAT
D1 peptide pre-treatment, signifying the behaviours were mediated by the D1-D2
heteromer. More importantly, in animals exposed to chronic unpredictable stress
(CUS), TAT-D1 peptide treatment alone induced significant and rapid anxiolytic
and antidepressant-like effects in two tests for CUS-induced anhedonia-like
reactivity and in the novelty-suppressed feeding test. Together these findings
indicate a positive role for the D1-D2 heteromer in mediating depression- and
anxiety-like behaviours and suggest its possible value as a novel therapeutic
target.
PMID- 26431908
TI - Preoperative High-Resolution Ultrasound for the Assessment of Malignant Central
Compartment Lymph Nodes in Papillary Thyroid Cancer.
AB - BACKGROUND: The identification and removal of malignant central compartment lymph
nodes (MCLN) is important to minimize the risk of persistent or recurrent local
disease in patients with papillary thyroid cancer (PTC). While the diagnostic
accuracy of preoperative ultrasound for the assessment of lateral compartment
node metastases is well recognized, its role in the identification of central
compartment node metastases in patients with PTC is less established. This study
delineates the utility of high-resolution ultrasound (HUS) for the assessment of
MCLN in patients with PTC. METHODS: A retrospective chart review was performed of
227 consecutive patients who underwent total thyroidectomy for biopsy-proven PTC
by a single endocrine surgeon in an academic tertiary care center between 2004
and 2014. Preoperative sonographic results were compared to postoperative
pathology reports to determine the accuracy of HUS for the assessment of MCLN.
Statistical analysis also included sensitivity, specificity, positive predictive
value (PPV), and negative predictive value (NPV). RESULTS: HUS identified
abnormal central compartment nodes in 51 (22.5%) patients. All 227 patients
underwent a careful central compartment node exploration. One hundred and four
(45.8%) patients had MCLN identified by surgery, of whom 65 (62.5%) had a
negative preoperative central compartment HUS. The sensitivity and specificity of
preoperative HUS for the assessment of MCLN were 0.38 and 0.90, respectively. The
PPV and NPV were 0.76 and 0.63, with an accuracy of 0.66. CONCLUSION:
Preoperative HUS is quite specific for the identification of MCLN in patients
with PTC. The present findings emphasize, however, that a negative HUS does not
obviate the need for careful exploration of the central compartment to minimize
the risk of persistent or recurrent local disease.
PMID- 26431909
TI - Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic
properties, and induces a contractile phenotype in smooth muscle cells.
AB - Biomaterials with the capacity to innately guide cell behaviour while also
displaying suitable mechanical properties remain a challenge in tissue
engineering. Our approach to this has been to utilise insoluble elastin in
combination with collagen as the basis of a biomimetic scaffold for
cardiovascular tissue engineering. Elastin was found to markedly alter the
mechanical and biological response of these collagen-based scaffolds.
Specifically, during extensive mechanical assessment elastin was found to reduce
the specific tensile and compressive moduli of the scaffolds in a concentration
dependant manner while having minimal effect on scaffold microarchitecture with
both scaffold porosity and pore size still within the ideal ranges for tissue
engineering applications. However, the viscoelastic properties were significantly
improved with elastin addition with a 3.5-fold decrease in induced creep strain,
a 6-fold increase in cyclical strain recovery, and with a four-parameter
viscoelastic model confirming the ability of elastin to confer resistance to long
term deformation/creep. Furthermore, elastin was found to result in the
modulation of SMC phenotype towards a contractile state which was determined via
reduced proliferation and significantly enhanced expression of early (alpha-SMA),
mid (calponin), and late stage (SM-MHC) contractile proteins. This allows the
ability to utilise extracellular matrix proteins alone to modulate SMC phenotype
without any exogenous factors added. Taken together, the ability of elastin to
alter the mechanical and biological response of collagen scaffolds has led to the
development of a biomimetic biomaterial highly suitable for cardiovascular tissue
engineering.
PMID- 26431910
TI - Gender-specific protective effect of the -463G>A polymorphism of myeloperoxidase
gene against the risk of essential hypertension in Russians.
AB - The purpose of this study was to investigate whether a common polymorphism
463G>A (rs2333227) in the promoter of myeloperoxidase (MPO) gene, an oxidant
enzyme producing hypohalogenic radicals, is associated with the risk of essential
hypertension (EH) in Russian population. A total of 2044 unrelated subjects
including 1256 EH patients and 788 normotensive controls were recruited for this
study. Genotyping of the MPO gene polymorphism was done using TaqMan-based assay.
A genotype -463GA was associated with decreased risk of EH (odds ratio = 0.82;
95% confidence interval: 0.68-1.00) at a borderline significance level (P = .05).
The gender-stratified analysis showed that a carriage of the -463GA and -463AA
genotypes is associated with decreased EH risk only in females (odds ratio =
0.74, 95% confidence interval: 0.56-0.96; P = .02). To the best of our knowledge,
this is the first study reporting a negative association between the -463G>A
polymorphism of the MPO gene and EH risk. Molecular mechanisms by which MPO gene
is involved in the pathogenesis of EH are discussed.
PMID- 26431911
TI - Effect of sulfide, osmotic, and thermal stresses on taurine transporter mRNA
levels in the gills of the hydrothermal vent-specific mussel Bathymodiolus
septemdierum.
AB - Hydrothermal vent environmental conditions are characterized by high sulfide
concentrations, fluctuating osmolality, and irregular temperature elevations
caused by vent effluents. These parameters represent potential stressors for
organisms that inhabit the area around hydrothermal vents. Here, we aimed to
obtain a better understanding of the adaptation mechanisms of marine species to
hydrothermal vent environments. Specifically, we examined the effect of sulfide,
osmolality, and thermal stress on the expression of taurine transporter (TAUT)
mRNA in the gill of the deep-sea mussel Bathymodiolus septemdierum, which is a
dominant species around hydrothermal vent sites. We analyzed TAUT mRNA levels by
quantitative real-time polymerase chain reaction (PCR) in the gill of mussels
exposed to sulfide (0.1 or 1mg/L Na2S.9H2O), hyper- (115% seawater) and hypo-
(97.5%, 95.5%, and 85% seawater) osmotic conditions, and thermal stresses (12
degrees C and 20 degrees C) for 24 and 48h. The results showed that mussels
exposed to relatively low levels of sulfide (0.1mg/L) and moderate heat stress
(12 degrees C) exhibited higher TAUT mRNA levels than the control. Although hyper
and hypo-osmotic stress did not significantly change TAUT mRNA levels, slight
induction was observed in mussels exposed to low osmolality. Our results indicate
that TAUT is involved in the coping mechanism of mussels to various hydrothermal
vent stresses.
PMID- 26431912
TI - The Tale of Two Hypoxia-Inducible Factors in Renal Cell Carcinoma.
PMID- 26431913
TI - Three-dimensional Printed Model of Prostate Anatomy and Targeted Biopsy-proven
Index Tumor to Facilitate Nerve-sparing Prostatectomy.
PMID- 26431914
TI - Re: Idir Ouzaid and Karim Bensalah. Results of the First Trial Assessing Adjuvant
Tyrosine Kinase Inhibitors in Renal Cell Carcinoma Do Not reASSURE. Eur Urol
2015;68:542-3.
PMID- 26431915
TI - Teaching, caring, and altruistic behaviors in toddlers.
AB - Peer-directed behaviors of toddlers were longitudinally recorded in a
naturalistic preschool setting. An observer (O, the first author) recorded
children's behaviors during play sessions with an IC recorder. One-year-old
children (N=13) and children under the age of 12 months (N=8) were observed for
15 min, 6 times in a year. Their teaching, caring, and altruistic behaviors were
analyzed in detail. Results indicated that peer-directed behaviors of one-year
olds increased dramatically. It is concluded that toddlers are sophisticated
social being.
PMID- 26431917
TI - Evaluation of extrashort 4-mm implants in mandibular edentulous patients with
reduced bone height in comparison with standard implants: a 12-month results.
AB - OBJECTIVE: The aim of this research was to evaluate the primary stability, the
marginal bone loss, the survival, and the success criteria, of 4-mm-length
implants compared with implants of conventional length supporting fixed
prostheses. MATERIALS AND METHODS: Ten patients were selected for treatment of
their atrophic edentulous jaws. Each patient received the following treatment:
six dental implants were inserted, two anterior implants of conventional length
(10-mm) in the interforaminal area and four posterior short implants of 4-mm
length (Standard Plus, Roxolid, SLActive, Institut Straumann AG). The implants
supported screw-retained fixed complete dentures. Examinations were conducted at
day 0, three, six, and twelve months after surgery for the evaluation of the
implant primary stability, secondary stability, crestal bone loss and survival by
clinical evaluations, insertion torque values, resonance frequency analysis
(RFA), and periapical radiography, respectively. RESULTS: Sixty implants were
inserted in ten patients. Mean insertion torque was slightly lower for 4-mm
implants than 10-mm implants (38.1 Ncm vs. 42.2 Ncm) but without statistically
significant difference. Implant stability was similar for extrashort and
conventional implants. Marginal bone loss was similar for both groups for all the
time periods. One short implant was lost before loading. The survival rates
twelve months after implant placement were of 97.5% and 100% for short and
conventional implants, respectively. Similarly, implant stability as measured by
RFA was nonsignificantly lower for the 4-mm implants compared to the 10-mm
implants. The marginal bone loss was lower for short implants three, six, and
twelve months after the surgery without statistical significant difference.
CONCLUSIONS: Within the limitations of this study, we conclude that short dental
implants (8 mm or less in length) supporting single crowns or fixed bridges are a
feasible treatment option with radiographic and clinical success rates similar to
longer implants for patients with compromised ridges. Long-term data with larger
number of implants and subjects are needed to confirm these preliminary results.
PMID- 26431916
TI - Combined circulating epigenetic markers to improve mesothelin performance in the
diagnosis of malignant mesothelioma.
AB - OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor
prognosis. A major challenge is the development and application of early and
highly reliable diagnostic marker(s). Serum biomarkers, such as 'soluble
mesothelin-related proteins' (SMRPs), is the most studied and frequently used in
MM. However, the low sensitivity of SMRPs for early MM limits its value;
therefore, additional biomarkers are required. In this study, two epigenetically
regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin
promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy
to detect MM at an early stage. MATERIALS AND METHODS: A total of 188 subjects,
including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls
were prospectively enrolled, serum samples collected, and serum levels of SMRPs,
miR-126 and Met-TM evaluated. Logistic regression analysis was performed to
evaluate the diagnostic value of the three biomarkers. Using this approach, the
performance of the '3-biomarker classifier' was tested by calculating the overall
probability score of the MM and control samples, respectively, and the ROC curve
was generated. RESULTS AND CONCLUSION: The combination of the three biomarkers
was the best predictor to differentiate MM patients from asbestos-exposed
subjects and healthy controls. The accuracy and cancer specificity was confirmed
in a second validation cohort and lung cancer population. We propose that the
combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early
MM overcomes the limitations of using SMRPs alone.
PMID- 26431918
TI - Low bone mineral density is associated with intracranial posterior circulation
atherosclerosis in women.
AB - Low bone mineral density (BMD) is associated with carotid atherosclerosis and the
incidence of stroke. However, there are no data on the association of BMD with
intracranial atherosclerosis. The study population consisted of 357 participants
who underwent dual energy x-ray absorptiometric scanning of the lumbar spine and
brain 3D time of flight magnetic resonance angiography as part of their voluntary
health checks. The basilar, middle cerebral, intracranial internal carotid and
intracranial vertebral arteries were evaluated. Low BMD was defined as a T-score
of less than -1. All analyses were stratified by sex and intracranial
atherosclerosis location. One hundred seventy-six women (53 years; 66.9%
postmenopausal; 33.5% low BMD; 60.2% intracranial atherosclerosis in the anterior
circulation (AC); 60.2% intracranial atherosclerosis in the posterior circulation
(PC)) and 181 men (51 years; 28.7% low BMD; 61.9% intracranial atherosclerosis in
the AC; 55.8% intracranial atherosclerosis in the PC) were included. In women,
low BMD was significantly associated with intracranial atherosclerosis in the PC
with the odds ratio of 2.57 (95% confidence interval 1.11-5.99). However,
intracranial atherosclerosis in the AC was not associated with BMD in women. In
men, there were no significant associations between BMD and intracranial
atherosclerosis. In conclusion, this study shows that low BMD is associated with
subclinical intracranial PC atherosclerosis in women but not in men.
PMID- 26431919
TI - Midterm Outcomes of Open Descending Thoracic Aortic Repair in More Than 5,000
Medicare Patients.
AB - BACKGROUND: Diseases involving the descending thoracic aorta (DTA) represent a
heterogeneous substrate with a variety of therapeutic options. Although thoracic
endovascular aortic repair has been increasingly applied to DTA disease, open
surgical repair is ostensibly more durable. METHODS: A total of 5,578 patients
who underwent open DTA repair (Current Procedural Terminology code 33875) from
1999 to 2010 were identified from the Medicare database; 5,489 patients had
complete data. Survival was assessed with Kaplan-Meier analysis. Cox regression
determined predictors of death. Hospital and surgeon volume and variability were
modeled, and their association with survival assessed. RESULTS: Median survival
after open DTA repair was only 4.3 years (95% confidence interval: 4.0 to 4.6).
The likelihood of death varied significantly by certain aortic diseases: aortic
rupture and acute aortic dissection patients had the highest early mortality.
Survival beyond 180 days was best for patients with acute aortic dissection and
isolated thoracic aortic aneurysm, and lowest for patients with thoracoabdominal
aneurysm and aortic rupture. Hospital and surgeon volume, as well as
interhospital and intersurgeon variability, had associations with overall
survival. CONCLUSIONS: Open DTA repair has treated a spectrum of aortic diseases
in Medicare beneficiaries. Overall mortality was high, predominately confined to
the initial postoperative hazard phase. Independent hospital and surgeon effects,
hospital and surgeon volume, and a more recent date of surgery correlated with
improved survival, while increased operative urgency and complexity correlated
with worse outcomes. These observations argue for regionalization of DTA
treatment for Medicare patients in specialized centers to concentrate expertise,
which should translate into better outcomes.
PMID- 26431920
TI - Effect of Hospital Volume on Prosthesis Use and Mortality in Aortic Valve
Operations in the Elderly.
AB - BACKGROUND: This study was designed to examine the effect of hospital procedural
volume on outcomes in aortic valve replacement (AVR) in the elderly. METHODS: The
study included 277,928 Medicare beneficiaries who underwent AVR from 2000 through
2009 at one of 1,255 participating hospitals. Operative mortality and the use of
mechanical prostheses were analyzed according to hospital annual procedural
volume. Annual AVR volume was divided into 5 different categories: the smallest
volume group with less than 10 AVRs per year to the largest group averaging more
than 70 AVRs per year. RESULTS: The overall observed operative mortality rate was
7.3%; for isolated AVR it was 5.5%. Lower-volume hospitals exhibited increased
adjusted operative mortality: 10 cases or fewer per year--odds ratio (OR), 1.55;
95% confidence interval (CI), 1.39 to 1.72; 11 to 20 cases per year--OR, 1.35;
95% CI, 1.23 to 1.47; 21 to 40 cases per year--OR, 1.15; 95% CI, 1.06 to 1.25; 41
to 70 cases per year--OR, 1.10; 95% CI, 1.01 to 1.20 relative to those hospitals
performing more than 70 cases per year. The discrepancy in operative mortality
between low- and high-volume hospitals diverged during the study. Mechanical
valve use decreased with increasing hospital volume (p = 0.0001). Mechanical
valves were used in 64.5% of AVRs in hospitals with an annual AVR volume less
than 10 in contrast to only 25.4% in hospitals with an annual AVR volume more
than 70. After adjustment, the use of mechanical valves was independently
associated with increased operative mortality (OR, 1.15; 95% CI, 1.11-1.19).
CONCLUSIONS: Low-volume centers were characterized by increased adjusted
operative mortality and greater use of mechanical prostheses, a trend that
persisted during the 10-year course of the study. These data would support the
center-of-excellence concept for AVR and may be particularly relevant in the
elderly population.
PMID- 26431921
TI - Survival After Extracorporeal Cardiopulmonary Resuscitation on Weekends in
Comparison With Weekdays.
AB - BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) requires urgent
decision-making and high-quality skills, which may not be uniformly available
throughout the week. Few data exist on the outcomes of patients with cardiac
arrest who receive in-hospital ECPR on the weekday versus weekend. Therefore, we
investigated whether the outcome differed when patients with in-hospital cardiac
arrest received ECPR during the weekend compared with a weekday. METHODS: Two
hundred patients underwent extracorporeal membrane oxygenation after in-hospital
cardiac arrest between January 2004 and December 2013. Patients treated between
0800 on Monday to 1759 on Friday were considered to receive weekday care and
patients treated between 1800 on Friday through 0759 on Monday were considered to
receive weekend care. RESULTS: A total of 135 cases of ECPR for in-hospital
cardiac arrest occurred during the weekday (64 during daytime hours and 71 during
nighttime hours), and 65 cases occurred during the weekend (39 during
daytime/evening hours and 26 during nighttime hours). Rates of survival to
discharge were higher with weekday care than with weekend care (35.8% versus
21.5%, p = 0.041). Cannulation failure was more frequent in the weekend group
(1.5% versus 7.7%, p = 0.038). Complication rates were higher on the weekend than
on the weekday, including cannulation site bleeding (3.0% versus 10.8%, p =
0.041), limb ischemia (5.9% versus 15.6%, p = 0.026), and procedure-related
infections (0.7% versus 9.2%, p = 0.005). CONCLUSIONS: ECPR on the weekend was
associated with a lower survival rate and lower resuscitation quality, including
higher cannulation failure and higher complication rate.
PMID- 26431922
TI - Adequacy Criteria of Rapid On-Site Evaluation for Endobronchial Ultrasound-Guided
Transbronchial Needle Aspiration: A Simple Algorithm to Assess the Adequacy of
ROSE.
AB - BACKGROUND: Rapid on-site evaluation (ROSE) for endobronchial ultrasound-guided
transbronchial needle aspiration (EBUS-TBNA) has been advocated to qualitatively
diagnose biopsy samples. However, adequate ROSE criteria during EBUS-TBNA are
unclear. The aim of this study was to determine adequacy criteria of ROSE in EBUS
TBNA samples and suggest an appropriate algorithm. METHODS: Patients who
underwent EBUS-TBNA for nodal evaluation between March and July 2013 at Seoul
National University Hospital were included prospectively. The ROSE slides were
reviewed independently by two pathologists, and the results were compared to the
final pathologic results. Diagnostic yields, sensitivity, specificity, and
accuracy were calculated in order to make nodal evaluations. RESULTS: EBUS-TBNA
was performed on 300 lymph nodes in 133 patients. Samples were nondiagnostic in
7.7%, 6.3%, and 1.7% of the cytologic, histologic, and overall pathologic
results, respectively. On the ROSE slides, a large tissue core size (>=2 cm),
microscopic anthracotic pigment (MAP), and increased lymphocyte density (LD; >=40
cells/field [40*, mean of 10 fields]) were significantly associated with adequate
final cytologic or histologic results. Malignant cells were not statistically
associated with adequacy but were considered a parameter indicating an adequate
diagnosis. Using four sequential criteria, tissue core size, the presence of
malignant cell, MAP, and LD >=40 cells/field, the sensitivity and accuracy rates
of ROSE increased from 64.4% to 98.6% and from 64.7% to 97.3%, respectively.
CONCLUSIONS: A high adequacy rate of ROSE in EBUS-TBNA can be achieved by
sequentially applying four criteria: tissue core size, malignant cells, MAP, and
increased LD.
PMID- 26431923
TI - Resected Tracheal Adenoid Cystic Carcinoma: Improvements in Outcome at a Single
Institution.
AB - BACKGROUND: Primary tracheal cancer comprises a heterogeneous and rare group of
neoplasms. Management of patients with primary tracheal carcinoma at our
institution has improved in recent years. METHODS: This retrospective review
included patients with localized primary tracheal adenoid cystic carcinoma
treated surgically at our institution between January 1995 and December 2014.
Patients were classified according to the timing of first operation: "early
years" operation was performed between January 1995 and December 2002, and
subsequent "recent years" operation was associated with improved management and a
focus on early diagnosis. RESULTS: The proportion of patients with tracheal
malignancy who underwent operation for adenoid cystic carcinoma increased with
time. Patients in the recent group were significantly younger than those in the
early group at diagnosis (49.3 +/- 7.8 years versus 45.7 +/- 9.4 years; p =
0.042), and the resected tumor size and tracheal lengths tended to be smaller
(28.2 +/- 7.6 mm versus 30.3 +/- 7.0 mm; p = 0.161) and shorter (32.1 +/- 7.7 mm
versus 34.4 +/- 6.7 mm; p = 0.123). The use of postoperative radiotherapy in
patients with R1 resection was also managed more effectively in the recent group
compared with the early group (90.6% versus 65.0%; p = 0.009). Five- and 10-year
overall survival rates in the early and recent groups were 86.4% and 90.8%, and
31.8% and 61.2%, respectively (p = 0.084), and the corresponding 5- and 10-year
disease-free survival rates were 39.7% and 75.3%, and 9.9% and 21.2%,
respectively (p = 0.025). CONCLUSIONS: There have been improved outcomes of
adenoid cystic carcinomas. Early diagnosis, experienced surgical treatments, and
postoperative adjuvant radiotherapy for patients with positive margins may
contribute to the improved survival of patients with primary tracheal adenoid
cystic carcinoma.
PMID- 26431924
TI - Long-Term Outcome and Predictors of Noninstitutionalized Survival Subsequent to
Prolonged Intensive Care Unit Stay After Cardiac Surgical Procedures.
AB - BACKGROUND: There are minimal data on long-term functional survival (alive and
not institutionalized) in patients undergoing cardiac operations who require a
prolonged intensive care unit length of stay (prICULOS). We sought to describe 1-
and 5-year functional survival in patients who had a prICULOS (ICULOS >= 5 days)
and determine predictors of functional survival at 1 year. METHODS: Data were
obtained from linked clinical and administrative databases from January 1, 2000
to December 31, 2011 to conduct this retrospective single-region analysis.
Logistic regression was used to develop a model predicting functional survival at
1 year for patients who had a prICULOS after cardiac operations. RESULTS: There
were 9,545 admissions to the ICU after cardiac operations; of these patients, 728
(7.6%) experienced a prICULOS. There was an increasing trend in patients who had
a prICULOS over this study period. The functional survival at 1 and 5 years from
the surgical procedure for the non-prICULOS versus the prICULOS cohort was 1 year
(94.9% versus 73.9%) and 5 years (84.9% versus 53.8%) (p < 0.001). Factors
associated with lower rates of functional survival at 1 year were age 80 years or
older, female sex, peripheral vascular disease, preoperative renal dysfunction,
cerebrovascular disease, preoperative infection, need for extracorporeal membrane
oxygenation/ventricular assist device (ECMO/VAD) after cardiotomy, number of days
on mechanical ventilation, and number of days in the ICU beyond 5 days (area
under the receiver operating characteristic [ROC] curve = 0.766). CONCLUSIONS:
The majority of patients who had a prICULOS experienced successful functional
survival up to 5 years after cardiac operations. Identification of risk factors
for poor functional survival may be of assistance to clinicians, patients, and
families for prognostication and decision making.
PMID- 26431925
TI - Hemodynamic Impact of Superior Vena Cava Placement in the Y-Graft Fontan
Connection.
AB - BACKGROUND: A Fontan Y-shaped graft using a commercially available aortoiliac
graft has been used to connect the inferior vena cava (IVC) to the pulmonary
arteries. This modification of the Fontan procedure seeks to improve hepatic flow
distribution (HFD) to the lungs. However, patient-specific anatomical
restrictions might limit the space available for graft placement. Altering the
superior vena cava (SVC) positioning is hypothesized to provide more space for an
optimal connection, avoiding caval flow collision. Computational modeling tools
were used to retrospectively study the effect of SVC placement on Y-graft
hemodynamics. METHODS: Patient-specific anatomies (N = 10 patients) and vessel
flows were reconstructed from retrospective cardiac magnetic resonance (CMR)
images after Fontan Y-graft completion. Alternative geometries were created using
a virtual surgery environment, altering the SVC position and the offset in
relation to the Y-graft branches. Geometric characterization and computational
fluid dynamics simulations were performed. Hemodynamic factors (power loss and
HFD) were computed. RESULTS: Patients with a higher IVC return showed less
sensitivity to SVC positioning. Patients with low IVC flow showed varied HFD
results, depending on SVC location. Balanced HFD values (50% to each lung) were
obtained when the SVC lay completely between the Y-graft branches. The effect on
power loss was patient specific. CONCLUSIONS: SVC positioning with respect to the
Y-graft affects HFD, especially in patients with lower IVC flow. Careful
positioning of the SVC at the time of a bidirectional Glenn (BDG) procedure based
on patient-specific anatomy can optimize the hemodynamics of the eventual Fontan
completion.
PMID- 26431926
TI - Sero-surveillance and risk factors for avian influenza and Newcastle disease
virus in backyard poultry in Oman.
AB - Avian Influenza (AI) and Newcastle disease (ND) are the most important reportable
poultry diseases worldwide. Low pathogenic AI (H9N2) and ND viruses are known to
have been circulating in the Middle East, including in Oman, for many decades.
However, detailed information on the occurrence of these pathogens is almost
completely lacking in Oman. As backyard poultry are not vaccinated against either
virus in Oman, this sector is likely to be the most affected poultry production
sector for both diseases. Here, in the first survey of AI and ND viruses in
backyard poultry in Oman, we report high flock-level seroprevalences of both
viruses. Serum and oropharyngeal swabs were taken from 2350 birds in 243 backyard
flocks from all regions and governorates of Oman. Information was recorded on
location, type of bird and housing type for each sampled farm. Individual bird
serum samples were tested using commercial indirect antibody detection ELISA
kits. Pooled oropharyngeal samples from each flock were inoculated onto FTA cards
and tested by RT-PCR. Samples came from chickens (90.5%), turkeys (2.1%), ducks
(6.2%), guinea fowl (0.8%) and geese (0.4%). The bird-level seroprevalence of
antibody to AI and ND viruses was 37.5% and 42.1% respectively, and at the flock
level it was 84% and 90% respectively. There were statistically significant
differences between some different regions of Oman in the seroprevalence of both
viruses. Flock-level NDV seropositivity in chickens was significantly associated
with AIV seropositivity, and marginally negatively associated with flock size.
AIV seropositivity in chickens was marginally negatively associated with
altitude. All oropharyngeal samples were negative for both viruses by RT-PCR,
consistent with a short duration of infection. This study demonstrates that eight
or nine out of ten backyard poultry flocks in Oman are exposed to AI and ND
viruses, and may present a risk for infection for the commercial poultry sector
in Oman, or wild birds which could carry infection further afield.
PMID- 26431928
TI - Spondyloarthritis: Criteria, limitations, and perspectives throughout history.
PMID- 26431927
TI - Role of mitochondrial oxidative stress on lymphocyte homeostasis in patients
diagnosed with extra-pulmonary tuberculosis.
AB - Extra-pulmonary tuberculosis is often an underrated illness. Recent clinical
studies have pointed out that lymphocyte homeostasis is dramatically disturbed as
revealed through a series of signs and symptoms. Lymphocytes, the known effector
cells of our immune system, play an important role in providing immunologic
resistance against Mycobacterium infection. It is important to have quantitative
insights into the lifespan of these cells; therefore, we aimed to study the
precise effect of gastrointestinal tuberculosis infection on peripheral blood
lymphocyte subpopulations and function. Our results indicated that
gastrointestinal tuberculosis could increase mitochondrial oxidative stress,
lower mitochondrial DNA copy number, promote nuclear DNA damage and repair
response, decrease mitochondrial respiratory chain enzyme activities, and
upregulate Bcl-2 and caspase-3 gene expression in lymphocytes. We further
revealed that Mycobacterium infection induces autophagy for selective
sequestration and subsequent degradation of the dysfunctional mitochondrion
before activating cellular apoptosis in the peripheral lymphocyte pool. Together,
these observations uncover a new role of mitochondrial-nuclear crosstalk that
apparently contributes to lymphocyte homeostasis in gastrointestinal tuberculosis
infection.
PMID- 26431929
TI - The impact of chronic low back pain is partly related to loss of social role: A
qualitative study.
AB - OBJECTIVES: Chronic low back pain (LBP) has an important impact on quality of
life, through pain and functional incapacity, but also psychosocial distress. The
social participation consequences of LBP have been less explored. The objective
was to better understand experiences of patients living with chronic LBP, with a
focus on impact on relationships with family, friends and work colleagues.
METHODS: Monocentric qualitative study in a tertiary-referral centre in Paris,
France. Participants had chronic mechanical LBP. Semi-structured interviews were
conducted during 4 focus groups discussions focusing on living with LBP. Verbatim
was categorized and coded using thematic content analysis. RESULTS: Twenty-five
persons (11 men, 14 women) participated; ages ranged 25-81 years. Participants
often reported a negative self-perception in social interactions, with shame and
frustration regarding their difficulties to perform activities of daily living.
They often felt misunderstood and unsupported, partly due to the absence of
visible signs of the condition. Participants suffered from the negative
collective image attached to LBP ("benign/psychological disease"). LBP resulted
in some patients in a significant loss of social identity with perceived
impossibility to perform one's social role at home and at work. In contrast,
family and friends were sometimes a support and helped in pain management.
CONCLUSION: A systematic assessment of social role is needed in LBP care.
PMID- 26431931
TI - Enthesitis: The clue to the pathogenesis of spondyloarthritis?
AB - The term "spondyloarthritis" designates a group of conditions whose shared
characteristic is inflammation at the interface between the bone and either the
tendons and ligaments or the joint capsule. This interface, known as the
enthesis, can be the site of ossification in spondyloarthritis. The advent of
high-performance imaging techniques such as magnetic resonance imaging has
rekindled interest in the enthesis by providing new insights into the sequence
that leads to entheseal ossification. These techniques have established initial
inflammation and fatty metaplasia as key events that precede ossification. The
pathophysiological mechanisms that trigger the initial inflammation probably
involve multiple factors such as mechanical stress and the presence of resident
cells responsive to interleukin-23 and capable of releasing proinflammatory
cytokines. Research into the triggers of entheseal inflammation and ossification
may thus provide the clue to the pathophysiology of spondyloarthritis.
PMID- 26431930
TI - Sodium (18)F-sodium fluoride PET failed to predict responses to TNFalpha
antagonist therapy in 31 patients with possible spondyloarthritis not meeting
ASAS criteria.
AB - OBJECTIVES: To determine whether (18)F-NaF positron-emission tomography (PET)
contributes to the diagnosis of spondyloarthritis and whether observed uptakes
predict the response to TNFalpha antagonist therapy. METHODS: We studied patients
who had suspected spondyloarthritis but did not meet ASAS criteria and who were
referred for an assessment of eligibility for TNFalpha antagonist therapy. (18)F
NaF PET was offered instead of bone scintigraphy. TNFalpha antagonist therapy was
given if the clinician's level of confidence in the diagnosis of
spondyloarthritis based on (18)F-NaF PET findings was >=50/100. RESULTS: Thirty
one patients accepted to undergo (18)F-NaF PET. Their mean age was 39.9+/-11.7
years; 22% were HLA-B27-positive and none had evidence of sacroiliitis by
magnetic resonance imaging. Of the 31 patients, 30 had abnormal (18)F-NaF PET
findings. However, of the 312 high-uptake foci, only 123 (39.4%) matched sites of
pain. TNFalpha antagonist therapy was given to 16 patients. The treated group and
untreated group (n=15) were not significantly different for the mean number of
high-uptake foci per patient (11.7+/-8.1 vs. 8.3+/-5.1, respectively) or for the
proportion of patients with high uptake by the sacroiliac joints (13/16 [81%] vs.
8/15 [53%], respectively). In the treated group, 5 patients met ASAS response
criteria after 3 months. These 5 patients were among the 9 treated patients who
met Amor's modified criteria (arthritis instead of asymmetrical oligoarthritis).
In the 5 responders, the (18)F-NaF uptake scores were nonsignificantly lower than
in the 11 nonresponders (9.0+/-8.5 vs. 13.0+/-6.4, respectively). In the patients
for whom the (18)F-NaF PET findings increased the level of confidence in the
diagnosis of spondyloarthritis, this effect was short-lived. DISCUSSION: The
positive predictive value of (18)F-NaF PET for diagnosing spondyloarthritis or
predicting a response to TNFalpha antagonist therapy seems very low. This finding
is probably ascribable to poor specificity.
PMID- 26431932
TI - The role of the neuropeptide Y (NPY) family in the pathophysiology of
inflammatory bowel disease (IBD).
AB - Inflammatory bowel disease (IBD) includes three main disorders: ulcerative
colitis, Crohn's disease, and microscopic colitis. The etiology of IBD is unknown
and the current treatments are not completely satisfactory. Interactions between
the gut neurohormones and the immune system are thought to play a pivot role in
inflammation, especially in IBD. These neurohormones are believed to include
members of the neuropeptide YY (NPY) family, which comprises NPY, peptide YY
(PYY), and pancreatic polypeptide (PP). Understanding the role of these peptides
may shed light on the pathophysiology of IBD and potentially yield an effective
treatment tool. Intestinal NPY, PYY, and PP are abnormal in both patients with
IBD and animal models of human IBD. The abnormality in NPY appears to be
primarily caused by an interaction between immune cells and the NPY neurons in
the enteric nervous system; the abnormalities in PYY and PP appear to be
secondary to the changes caused by the abnormalities in other gut neurohormonal
peptides/amines that occur during inflammation. NPY is the member of the NPY
family that can be targeted in order to decrease the inflammation present in IBD.
PMID- 26431934
TI - Trends Form Follows Function: New Ways to Inform and Inspire.
PMID- 26431933
TI - Elevated levels of neuropeptide Y in preeclampsia: A pilot study implicating a
role for stress in pathogenesis of the disease.
AB - OBJECTIVE: To determine if preeclampsia (PE) is associated with dysregulation of
the neuropeptide Y (NPY) system. METHODS: The study enrolled 114 subjects either
with normal pregnancy (NP) or with PE. Systolic blood pressure (SBP) was
collected from patients using a standard sphygmomanometer. The PE patients were
divided into two groups based on the gestational age (GA) at delivery - placental
PE (PLPE, GA <34 weeks) or maternal PE (MTPE, GA >=34 weeks). NPY was measured in
platelet rich plasma (PRP), platelet poor plasma (PPP) and in the serum of NP and
PE patients utilizing radioimmunoassay. Serum levels of soluble fms-like tyrosine
kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in NP and PE
subjects by ELISA. RESULTS: SBP was higher in PE compared to NP. Circulating NPY
in serum and PRP, as well as NPY content per 100,000 platelets, but not its
concentrations in PPP, were elevated in PE, as compared to NP. The highest NPY
concentrations were observed in sera and PRP of patients with MTPE. PE patients
had also elevated levels of sFlt-1, as compared to NP, although no difference
between PLPE and MTPL groups were observed. There was no increase in P1GF in PE
patients. CONCLUSION: Systemic NPY is elevated in PE patients, as compared to NP.
This increase is observed in blood fractions containing platelets, suggesting
accumulation of the peptide in these cells. NPY concentrations are particularly
high in patients with MTPE, underlying differences in etiology between PLPE and
MTPE. Our study implicates NPY as a potential target in antihypertensive
therapies for PE patients.
PMID- 26431935
TI - A Learning Experience.
PMID- 26431936
TI - Revisiting the Mechanisms of CNS Immune Privilege.
AB - Whereas the study of the interactions between the immune system and the central
nervous system (CNS) has often focused on pathological conditions, the importance
of neuroimmune communication in CNS homeostasis and function has become clear
over that last two decades. Here we discuss the progression of our understanding
of the interaction between the peripheral immune system and the CNS. We examine
the notion of immune privilege of the CNS in light of both earlier findings and
recent studies revealing a functional meningeal lymphatic system that drains
cerebrospinal fluid (CSF) to the deep cervical lymph nodes, and consider the
implications of a revised perspective on the immune privilege of the CNS on the
etiology and pathology of different neurological disorders.
PMID- 26431939
TI - Microglia Plasticity During Health and Disease: An Immunological Perspective.
AB - Microglia are macrophages of the central nervous system (CNS) that continuously
scrutinize their environment for damage. They colonize the cephalic mesenchyme
during embryogenesis and actively shape the developing neuronal network by immune
mediated mechanisms. Upon CNS maturation, microglia drastically change phenotype
and function. During health, adult microglia contribute to homeostasis, but also
the establishment and resolution of inflammatory conditions. Fulfillment of these
distinct tasks requires these long-lived cells to accurately adjust to their
changing environment. Deciphering microglia responsiveness to divergent stimuli
is central to understanding this cell type and for eventual microglia
manipulation to potentially reduce disease burden. Here we discuss new aspects of
myeloid cell biology in general with special emphasis on the shifting role of
microglia during establishment and protection of CNS integrity.
PMID- 26431938
TI - Microglia: Dynamic Mediators of Synapse Development and Plasticity.
AB - Neuronal communication underlies all brain activity and the genesis of complex
behavior. Emerging research has revealed an unexpected role for immune molecules
in the development and plasticity of neuronal synapses. Moreover microglia, the
resident immune cells of the brain, express and secrete immune-related signaling
molecules that alter synaptic transmission and plasticity in the absence of
inflammation. When inflammation does occur, microglia modify synaptic connections
and synaptic plasticity required for learning and memory. Here we review recent
findings demonstrating how the dynamic interactions between neurons and microglia
shape the circuitry of the nervous system in the healthy brain and how altered
neuron-microglia signaling could contribute to disease.
PMID- 26431940
TI - Homeostasis of Microglia in the Adult Brain: Review of Novel Microglia Depletion
Systems.
AB - Microglia are brain macrophages that emerge from early erythro-myeloid precursors
in the embryonic yolk sac and migrate to the brain mesenchyme before the blood
brain barrier is formed. They seed the brain, and proliferate until they have
formed a grid-like distribution in the central nervous system that is maintained
throughout lifespan. The mechanisms through which these embryonic-derived cells
contribute to microglia homoeostasis at steady state and upon inflammation are
still not entirely clear. Here we review recent studies that provided insight
into the contribution of embryonically-derived microglia and of adult 'microglia
like' cells derived from monocytes during inflammation. We examine different
microglia depletion models, and discuss the origin of their rapid repopulation
after depletion and outline important areas of future research.
PMID- 26431937
TI - The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis
and Disease.
AB - The nervous system and the immune system are the principal sensory interfaces
between the internal and external environment. They are responsible for
recognizing, integrating, and responding to varied stimuli, and have the capacity
to form memories of these encounters leading to learned or 'adaptive' future
responses. We review current understanding of the cross-regulation between these
systems. The autonomic and somatosensory nervous systems regulate both the
development and deployment of immune cells, with broad functions that impact on
hematopoiesis as well as on priming, migration, and cytokine production. In turn,
specific immune cell subsets contribute to homeostatic neural circuits such as
those controlling metabolism, hypertension, and the inflammatory reflex. We
examine the contribution of the somatosensory system to autoimmune,
autoinflammatory, allergic, and infectious processes in barrier tissues and, in
this context, discuss opportunities for therapeutic manipulation of neuro-immune
interactions.
PMID- 26431942
TI - GM-CSF in Neuroinflammation: Licensing Myeloid Cells for Tissue Damage.
AB - Multiple sclerosis (MS) is the prototypical inflammatory disease of the central
nervous system (CNS). MS lesions harbor different immune cells, but the
contribution of individual cell types to disease etiology and progression is not
well understood. In experimental autoimmune encephalomyelitis (EAE), auto
reactive helper T (Th) cells instigate CNS inflammation by acting on myeloid
cells via the production of granulocyte-macrophage colony-stimulating factor (GM
CSF). Recent reports have implicated myeloid cells in both the inflammatory
process and as executers of tissue damage in the CNS. We review these findings
here, and integrate them into a model wherein GM-CSF produced by Th cells
coordinates monocyte recruitment to the CNS, and differentiation into pathogenic
effectors. We discuss the implications of this model to current therapies for MS,
and outline important areas of further inquiry.
PMID- 26431943
TI - First Detection of Antibodies Against African Swine Fever Virus in Faeces
Samples.
AB - African swine fever (ASF) is a viral, highly lethal haemorrhagic disease of swine
with no available vaccine or effective treatment. Introduction of ASF into a
country triggers immediate restriction measures that cause significant economic
losses and threatens spread to neighbouring countries. Wild boar populations have
been recently assigned an essential role in the spread of African swine fever
virus (ASFV) to European countries. Therefore, effective surveillance and
monitoring of wild boar populations is required, but sampling wild boar is
logistically challenging and expensive. This study assessed the feasibility of
detecting antibodies against ASFV in faeces for later implementation in
surveillance and control programmes. Two groups of pigs were experimentally
infected with an attenuated ASFV isolate Ken05, and blood, oral fluid and faecal
samples were tested for the presence of viral DNA using quantitative real-time
polymerase chain reaction (qPCR) to monitor infection progress. Faecal samples
were analysed using two indirect enzyme-linked immunosorbent assays (ELISAs)
based on semipurified viral protein (vp) 72 or purified recombinant vp30
expressed in mammalian cells. Faecal samples from 9 of 10 pigs with non
haemorrhagic diarrhoea tested positive for antibodies against ASFV using the two
ELISA tests that showed a positive correlation. The serum sample results from the
two indirect ELISAs were compared against results from the reference ELISA
technique and the immunoperoxidase test. Our findings indicate the feasibility of
faecal sampling for detecting anti-ASFV antibodies, which may provide a practical
non-invasive alternative for sampling wild boar populations. In conclusion, the
application of these ELISA tests to faecal field samples could be particularly
useful to screen for the presence of ASF in field conditions.
PMID- 26431944
TI - Meningoencephalitis caused by septic arthritis of a lumbar facet joint in a
patient without fever or risk factors.
PMID- 26431941
TI - Immune Surveillance of the CNS following Infection and Injury.
AB - The central nervous system (CNS) contains a sophisticated neural network that
must be constantly surveyed in order to detect and mitigate a diverse array of
challenges. The innate and adaptive immune systems actively participate in this
surveillance, which is critical for the maintenance of CNS homeostasis and can
facilitate the resolution of infections, degeneration, and tissue damage.
Infections and sterile injuries represent two common challenges imposed on the
CNS that require a prompt immune response. While the inducers of these two
challenges differ in origin, the resultant responses orchestrated by the CNS
share some overlapping features. Here, we review how the CNS immunologically
discriminates between pathogens and sterile injuries, mobilizes an immune
reaction, and, ultimately, regulates local and peripherally-derived immune cells
to provide a supportive milieu for tissue repair.
PMID- 26431945
TI - Rescuer factors predict high-quality CPR--a manikin-based study of health care
providers.
AB - BACKGROUND: In the provision of high-quality cardiopulmonary resuscitation (CPR)
by health care providers, factors associated with high-quality CPR should be
explored. METHODS: This is a post hoc analysis using data from a manikin-based
survey of CPR quality among volunteer emergency medical technicians (EMTs) from 2
county fire departments in northern Taiwan. RESULTS: Among the 95 enrolled EMTs,
36 (37.9%) performed high-quality CPR on a manikin. The baseline characteristics
that differed significantly between groups were board-certified EMT levels (P =
.010), body mass index (BMI, P = .029), average exercise frequency (P = .001),
and average exercise duration (P = .005). Average total exercise time per week,
which uses frequency times exercise duration, was independently associated with
high-quality CPR performance after adjusting for variables via logistic
regression analysis (odds ratio, 1.004; P = .044). An index was developed (BMI *
ExeTime) based on the product of BMI and average total exercise time per week. A
comparison of the area under curve for the different indices showed that BMI *
ExeTime was a significant predictor of high-quality CPR, with an area under curve
of 0.718 (95% confidence interval, 0.613-0.824; P < .001; Fig. 2) and a cutoff
value of 4136.7 kg.min/m(2) (sensitivity, 0.722; specificity, 0.678).
CONCLUSIONS: This study identified factors associated with the performance by
health care providers of high-quality CPR, including BMI and exercise habits. To
optimize CPR quality, a program of exercise frequency and duration adjusted
according to individual's BMI should be considered in such populations.
PMID- 26431946
TI - Establishing diversity in the dopaminergic system.
AB - Midbrain dopaminergic neurons (MbDNs) modulate cognitive processes, regulate
voluntary movement, and encode reward prediction errors and aversive stimuli.
While the degeneration of MbDNs underlies the motor defects in Parkinson's
disease, imbalances in dopamine levels are associated with neuropsychiatric
disorders such as depression, schizophrenia and substance abuse. In recent years,
progress has been made in understanding how MbDNs, which constitute a relatively
small neuronal population in the brain, can contribute to such diverse functions
and dysfunctions. In particular, important insights have been gained regarding
the distinct molecular, neurochemical and network properties of MbDNs. How this
diversity of MbDNs is established during brain development is only starting to be
unraveled. In this review, we summarize the current knowledge on the diversity in
MbDN progenitors and differentiated MbDNs in the developing rodent brain. We
discuss the signaling pathways, transcription factors and transmembrane receptors
that contribute to setting up these diverse MbDN subpopulations. A better insight
into the processes that establish diversity in MbDNs will ultimately improve the
understanding of the architecture and function of the dopaminergic system in the
adult brain.
PMID- 26431947
TI - Differential Roles for Interleukin-23 and Interleukin-17 in Intestinal
Immunoregulation.
AB - Interleukin-23 (IL-23) and IL-17 are cytokines currently being targeted in
clinical trials. Although inhibition of both of these cytokines is effective for
treating psoriasis, IL-12 and IL-23 p40 inhibition attenuates Crohn's disease,
whereas IL-17A or IL-17 receptor A (IL-17RA) inhibition exacerbates Crohn's
disease. This dichotomy between IL-23 and IL-17 was effectively modeled in the
multidrug resistance-1a-ablated (Abcb1a(-/-)) mouse model of colitis. IL-23
inhibition attenuated disease by decreasing colonic inflammation while enhancing
regulatory T (Treg) cell accumulation. Exacerbation of colitis by IL-17A or IL
17RA inhibition was associated with severe weakening of the intestinal epithelial
barrier, culminating in increased colonic inflammation and accelerated mortality.
These data show that IL-17A acts on intestinal epithelium to promote barrier
function and provide insight into mechanisms underlying exacerbation of Crohn's
disease when IL-17A or IL-17RA is inhibited.
PMID- 26431948
TI - Interleukin-23-Independent IL-17 Production Regulates Intestinal Epithelial
Permeability.
AB - Whether interleukin-17A (IL-17A) has pathogenic and/or protective roles in the
gut mucosa is controversial and few studies have analyzed specific cell
populations for protective functions within the inflamed colonic tissue. Here we
have provided evidence for IL-17A-dependent regulation of the tight junction
protein occludin during epithelial injury that limits excessive permeability and
maintains barrier integrity. Analysis of epithelial cells showed that in the
absence of signaling via the IL-17 receptor adaptor protein Act-1, the protective
effect of IL-17A was abrogated and inflammation was enhanced. We have
demonstrated that after acute intestinal injury, IL-23R(+) gammadelta T cells in
the colonic lamina propria were the primary producers of early, gut-protective IL
17A, and this production of IL-17A was IL-23 independent, leaving protective IL
17 intact in the absence of IL-23. These results suggest that IL-17-producing
gammadelta T cells are important for the maintenance and protection of epithelial
barriers in the intestinal mucosa.
PMID- 26431950
TI - Impact of maternal nutritional status before and during pregnancy on neonatal
body composition: A cross-sectional study.
AB - BACKGROUND: The existence of early factors which, acting during critical periods
of intrauterine or immediate postnatal development, determine long-term health
has become increasingly recognized. Both high and low birth weight have been
associated with cardiovascular risk factors in adulthood. Therefore, body
composition at birth rather than birth weight may be a marker to predict future
diseases. Maternal weight previous to and gained during pregnancy is associated
with intrauterine fetal growth. OBJECTIVE: To evaluate the correlation between
maternal nutritional status before and during pregnancy and neonatal body
composition. MATERIAL AND METHODS: We studied consecutive mother-child pairs at
delivery at an Argentinean public hospital during 5 months period, evaluating
maternal and neonatal anthropometry before 24h of life as well as the history of
the mother before and during pregnancy. Neonatal body composition was calculated
according to a mathematical formula based on skinfold thickness measurement
validated in newborns. RESULTS: Mothers of newborns with high body fat mass were
more frequently obese (72.7% versus 35.1%, p 0.005), and more frequently showed
weight gain above 18kg during pregnancy (76.4% versus 31%, p 0.03). CONCLUSIONS:
Our findings confirm the hypothesis that maternal obesity before pregnancy is
highly correlated with neonatal fat mass in the first hours of life.
PMID- 26431949
TI - T Follicular Helper Cell-Dependent Clearance of a Persistent Virus Infection
Requires T Cell Expression of the Histone Demethylase UTX.
AB - Epigenetic changes, including histone methylation, control T cell differentiation
and memory formation, though the enzymes that mediate these processes are not
clear. We show that UTX, a histone H3 lysine 27 (H3K27) demethylase, supports T
follicular helper (Tfh) cell responses that are essential for B cell antibody
generation and the resolution of chronic viral infections. Mice with a T cell
specific UTX deletion had fewer Tfh cells, reduced germinal center responses,
lacked virus-specific immunoglobulin G (IgG), and were unable to resolve chronic
lymphocytic choriomeningitis virus infections. UTX-deficient T cells showed
decreased expression of interleukin-6 receptor-alpha and other Tfh cell-related
genes that were associated with increased H3K27 methylation. Additionally, Turner
Syndrome subjects, who are predisposed to chronic ear infections, had reduced UTX
expression in immune cells and decreased circulating CD4(+) CXCR5(+) T cell
frequency. Thus, we identify a critical link between UTX in T cells and immunity
to infection.
PMID- 26431951
TI - Perioperative stroke in patients undergoing elective spinal surgery: a
retrospective analysis using the Japanese diagnosis procedure combination
database.
AB - BACKGROUND: Although a few studies on perioperative stroke following spinal
surgery have been reported, differences in the incidence of perioperative stroke
among various surgical procedures have not been determined. The purpose of this
retrospective analysis was to investigate the incidence of perioperative stroke
during hospitalization in patients undergoing elective spinal surgery, and to
examine whether the incidence varied according to the surgical procedure.
METHODS: A retrospective analysis of data from the Diagnosis Procedure
Combination database, a nationwide administrative impatient database in Japan,
identified 167,106 patients who underwent elective spinal surgery during 2007
2012. Patient information extracted included age, sex, preoperative comorbidity,
administration of blood transfusion, length of hospitalization, and type of
hospital. Clinical outcomes included perioperative stroke during hospitalization,
and in-hospital death. RESULTS: The overall incidence of perioperative stroke was
0.22 % (371/167,106) during hospitalization. A logistic regression model fitted
with a generalized estimating equation showed perioperative stroke was associated
with advanced age, a history of cardiac disease, an academic institution, and
resection of a spinal tumor. Patients who underwent resection of a spinal cord
tumor (reference) had a higher risk of stroke compared with those undergoing
discectomy (odds ratio (OR), 0.29; 95 % confidence interval (CI), 0.14-0.58; p =
0.001), decompression surgery (OR, 0.44; 95 % CI, 0.26-0.73; p = 0.001), or
arthrodesis surgery (OR, 0.55; 95 % CI, 0.34-0.90); p = 0.02). Advanced age (>=80
years; OR, 5.66; 95 % CI, 3.10-10.34; p <= 0.001), history of cardiac disease
(OR, 1.58; 95 % CI, 1.10-2.26; p = 0.01), diabetes (OR, 1.73; 95 % CI, 1.36-2.20;
p <= 0.001), hypertension (OR, 1.53; 95 % CI, 1.18-1.98; p = 0.001), cervical
spine surgery (OR, 1.44; 95 % CI, 1.09-1.90; p = 0.01), a teaching hospital (OR,
1.36; 95 % CI, 1.01-1.82; p = 0.04), and length of stay (OR, 1.008; 95 % CI,
1.005-1.010; p <= 0.001) were also risk factors for perioperative stroke.
CONCLUSIONS: Perioperative stroke occurred in 0.22 % of patients undergoing
spinal surgery. Resection of a spinal cord tumor was associated with increased
risk of perioperative stroke as well as advanced age, comorbidities at admission,
cervical spine surgery, surgery in a teaching hospital, and length of stay.
PMID- 26431952
TI - Feasibility of Using an Enzymatically Activatable Fluorescence Probe for the
Rapid Evaluation of Pancreatic Tissue Obtained Using Endoscopic Ultrasound-Guided
Fine Needle Aspiration: a Pilot Study.
AB - PURPOSE: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the
most reliable method for the histological diagnosis of pancreatic tumors. Rapid
on-site fluorescence-guided histological diagnosis was evaluated by topically
applying an enzymatically activatable probe onto the EUS-FNA samples; the probe
fluoresces in the presence of gamma-glutamyltranspeptidase (GGT). PROCEDURES: We
evaluated GGT expression in pancreatic cancer cell lines in vitro. EUS-FNA was
performed in 10 pancreatic tumors. After topical application of the probe, signal
intensity was measured using a fluorescence imaging system for 13 min. RESULTS:
GGT was expressed in Panc-1, AsPC-1, and AR42J, but not in KP4 cells. In samples
from six cases, several regions of the specimens fluoresced and contained
adequate tissue for pathological diagnosis. The remaining four non-fluorescent
samples contained very small amounts of carcinoma, normal epithelial cells, or no
epithelial cells. The signal intensity at 5 min was 25.5 +/- 7.7 and 7.7 +/- 0.5
in fluorescent and non-fluorescent regions, respectively (p < 0.05). CONCLUSIONS:
Application of enzymatically activatable probe onto EUS-FNA samples would be
feasible for the rapid evaluation of tissues suitable for histological diagnosis.
PMID- 26431954
TI - The impact of Alpha/ESHRE consensus regarding oocytes with aggregates of smooth
endoplasmic reticulum (SERa) on in vitro fertilization outcome.
AB - PURPOSE: The present study aimed to gather information on the impact of
Alpha/European Society of Human Reproduction and Embryology (ESHRE) consensus
regarding oocytes with aggregates of smooth endoplasmic reticulum (SERa) on in
vitro fertilization outcome. In particular, we investigated if patients
undergoing intracytoplasmic sperm injection (ICSI) and whose oocytes are
discarded due to SERa have a higher chance of embryo transfer cancellation
compared to patients without SERa oocytes. METHODS: This is a nested case-control
study drawn from the cohort of women referring for in vitro fertilization with
ICSI. Cases were patients showing at least one oocyte with SERa at the time of
injection. Controls were subsequent patients showing no SERa oocytes and matched
ratio 1:1 for age, clinical indication to in vitro fertilization (IVF), and body
mass index. The main outcome was the rate of embryo transfer cancellation.
RESULTS: The percentage of women experiencing a transfer cancellation (absence of
suitable oocytes or viable embryos) in their ICSI cycle were significantly higher
in cases (18 %) compared to controls (8 %) (p = 0.02); however, adjusted odds
ratio for FSH and number of SERa oocytes, of follicles, of retrieved oocytes, and
of inseminated oocytes were not statistically significant. CONCLUSIONS: We have
shown that the exclusion of SERa oocytes from ICSI cycles causes an increased
frequency of transfer cancellation. This effect is mostly due to the reduced
number of available oocytes after exclusion of SERa oocytes.
PMID- 26431953
TI - [Injection treatment with hyaluronic acid].
AB - This article presents the spectrum of indications for the use of hyaluronic acid
(HA) based on the recommendations of the European League Against Rheumatism
(EULAR), the American College of Rheumatology (ACR), the Osteoarthritis Research
Society International (OARSI), the International Institute for Health and
Clinical Excellence (NICE) and the European Society for Clinical and Economic
Aspects of Osteoporosis and Osteoarthritis (ESCEO) taking the reality of patient
care in Europe into account.
PMID- 26431955
TI - Reference values of reactive oxygen species in seminal ejaculates using
chemiluminescence assay.
AB - PURPOSE: A physiological balance exists between seminal reactive oxygen species
(ROS) and antioxidant capacity. An overproduction of ROS which exceeds the
seminal plasma antioxidant capacity results in oxidative stress (OS). The aim of
the present study was to describe a detailed protocol to measure ROS in a
diagnostic laboratory and revise our previous cutoff value of ROS in seminal
ejaculates in a larger cohort of infertile men and controls with proven and
unproven fertility. METHODS: A total of 258 infertile men and 92 controls were
enrolled in the study. Following initial semen analysis, ROS measurement in whole
ejaculates was carried out using luminol-based chemiluminescence assay.
Chemiluminescence was measured for 15 min with a Berthold luminometer. Results
were expressed as relative light units (RLU/s/10(6) sperm). The test's
specificity, sensitivity, and cutoff values were calculated using the receiver
operating characteristic (ROC) curve. RESULTS: Significantly higher ROS levels
were seen in infertile men compared to controls (p < 0.001). The optimal cutoff
value to differentiate between controls and infertile men was 102.2 RLU/s/10(6)
sperm. At this cutoff value, the test was 76.4% sensitive and 53.3% specific. The
positive and negative predictive values of the test were 82.1% and 44.5%,
respectively. A total of 76.4% infertile population was above this cutoff value
compared to 46.7% of controls. CONCLUSIONS: The luminol-based chemiluminescence
assay can be used in routine diagnostic screening to test for male infertility
diagnosis in a clinical setting. The current ROS cutoff value substantially
distinguishes infertile from normal controls. Patients with elevated ROS must be
evaluated for the underlying cause of ROS production.
PMID- 26431957
TI - Juice Boxes.
PMID- 26431956
TI - Clostridial Infections in Children: Spectrum and Management.
AB - Clostridia can cause unique histotoxic syndromes produced by specific toxins
(e.g., gas gangrene and food poisoning) as well as non-syndromic infections
(e.g., abscess, local infections, and blood born infection). Clostridia can also
be recovered from various body sites as part of polymicrobial aerobic-anaerobic
infection. These include intra-abdominal (peritonitis and abscess), biliary
tract, female genital tract, abscess (rectal area and oropharyngeal),
pleuropulmonary, central nervous system, and skin and soft-tissue infections.
Clostridia were recovered from children with bacteremia of gastrointestinal
origin, necrotizing enterocolitis, and sickle cell disease. They have also been
isolated in acute and chronic otitis media, chronic sinusitis and mastoiditis,
peritonsillar abscesses, and neonatal conjunctivitis. Early and aggressive
surgical debridement, decompression, and drainage of affected tissues are
critical to successful outcome of histotoxic infections. Effective antimicrobials
include penicillin, clindamycin, chloramphenicol, third-generation
cephalosporins, carbapenems, and vancomycin.
PMID- 26431958
TI - Analgesia-free flexible ureteroscopic treatment and laser lithotripsy for removal
of a large urinary stone: a case report.
AB - INTRODUCTION: Urinary stone formation is a frequent complication after continent
urinary tract diversion and can require complex surgical management. Therapy
options include open, percutaneous, transurethral, or transstomal stone
fragmentation and extraction. The transstomal approach is considered to be one of
the more complex treatment modalities. The patient's individual anatomy, minor
stoma diameter, and the existing continence mechanism in the majority of cases
cause substantial technical challenges for the surgeon. We present here what we
believe to be the first description of an analgesia-free flexible endoscopic
removal of a large pouch stone in an out-patient care setting. Additionally, we
provide a brief overview of competing techniques. CASE PRESENTATION: A 30-year
old Caucasian woman with a history of lower urinary tract reconstruction with an
ileal pouch and a continent umbilical stoma was admitted to our department with
pouch urolithiasis in the urinary reservoir. We employed a minimally invasive
approach to extract the stone using flexible ureteroscopy via a modified access
sheath and laser lithotripsy. No analgesia is needed with this procedure and it
can be performed in an out-patient setting. CONCLUSION: The described clinical
case highlights the difficulties of treating this high-incidence problem in
patients with continent urinary diversions. Our presented technique is of
particular interest to urologists and family doctors, and could improve the
treatment of such patients by lowering the morbidity of the intervention.
PMID- 26431959
TI - Validation of the Dutch version of the quick mild cognitive impairment screen
(Qmci-D).
AB - BACKGROUND: Differentiating mild cognitive impairment (MCI) from dementia is
important, as treatment options differ. There are few short (<5 min) but accurate
screening tools that discriminate between MCI, normal cognition (NC) and
dementia, in the Dutch language. The Quick Mild Cognitive Impairment (Qmci)
screen is sensitive and specific in differentiating MCI from NC and mild
dementia. Given this, we adapted the Qmci for use in Dutch-language countries and
validated the Dutch version, the Qmci-D, against the Dutch translation of the
Standardised Mini-Mental State Examination (SMMSE-D). METHOD: The Qmci was
translated into Dutch with a combined qualitative and quantitative approach. In
all, 90 participants were recruited from a hospital geriatric clinic (25 with
dementia, 30 with MCI, 35 with NC). The Qmci-D and SMMSE-D were administered
sequentially but randomly by the same trained rater, blind to the diagnosis.
RESULTS: The Qmci-D was more sensitive than the SMMSE-D in discriminating MCI
from dementia, with a significant difference in the area under the curve (AUC),
0.73 compared to 0.60 (p = 0.024), respectively, and in discriminating dementia
from NC, with an AUC of 0.95 compared to 0.89 (p = 0.006). Both screening
instruments discriminated MCI from NC with an AUC of 0.86 (Qmci-D) and 0.84
(SMMSE-D). CONCLUSION: The Qmci-D shows similar,(good) accuracy as the SMMSE-D in
separating NC from MCI; greater,(albeit fair), accuracy differentiating MCI from
dementia, and significantly greater accuracy in separating dementia from NC.
Given its brevity and ease of administration, the Qmci-D seems a useful cognitive
screen in a Dutch population. Further study with a suitably powered sample
against more sensitive screens is now required.
PMID- 26431960
TI - SIADH-related hyponatremia in hospital day care units: clinical experience and
management with tolvaptan.
AB - Hyponatremia (Na ? 135 mmol/l) is the most frequent electrolyte disorder in
clinical practice, and the syndrome of inappropriate antidiuretic hormone
secretion (SIADH) is the commonest cause of hyponatremia in cancer patients.
Correcting hyponatremia in these patients can reduce morbidity and mortality,
increase the response to anti-cancer agents, and help reduce hospital length of
stay and costs. Tolvaptan is an oral medication used to treat SIADH-related
hyponatremia patients that needs to be initiated at hospital so patients can have
their serum sodium monitored. If tolvaptan could be initiated in hospital day
care units (DCUs), performing the same tests, hospitalization could be avoided,
quality of life improved, and costs reduced. This is the first publication where
a panel of oncologists are sharing their experience and making some
recommendations with the use of tolvaptan to treat SIADH-related hyponatremia in
DCU after collecting and examining 35 clinical cases with these type of patients.
The conclusion from this retrospective observational analysis is that the use of
tolvaptan in DCU is safe and effective in the therapeutic management of SIADH
related hyponatremia.
PMID- 26431961
TI - How effective are common medications: a perspective based on meta-analyses of
major drugs.
AB - The vastness of clinical data and the progressing specialization of medical
knowledge may lead to misinterpretation of medication efficacy. To show a
realistic perspective on drug efficacy we present meta-analyses on some of the
most commonly used pharmacological interventions. For each pharmacological
intervention we present statistical indexes (absolute risk or response
difference, percentage response ratio, mean difference, standardized mean
difference) that are often used to represent efficacy. We found that some of the
medications have relatively low effect sizes with only 11 out of 17 of them
showing a minimal clinically important difference. Efficacy was often established
based on surrogate outcomes and not the more relevant patient-oriented outcomes.
As the interpretation of the efficacy of medication is complex, more training for
physicians might be needed to get a more realistic view of drug efficacy. That
could help prevent harmful overtreatment and reinforce an evidence-based, but
personalized medicine.
PMID- 26431962
TI - Older people are not a burden, says WHO.
PMID- 26431964
TI - Avian migrants facilitate invasions of neotropical ticks and tick-borne pathogens
into the United States.
AB - Migratory birds have the potential to transport exotic vectors and pathogens of
human and animal health importance across vast distances. We systematically
examined birds that recently migrated to the United States from the Neotropics
for ticks. We screened both ticks and birds for tick-borne pathogens, including
Rickettsia species and Borrelia burgdorferi. Over two spring seasons (2013 and
2014), 3.56% of birds (n = 3,844) representing 42.35% of the species examined (n
= 85) were infested by ticks. Ground-foraging birds with reduced fuel stores were
most commonly infested. Eight tick species were identified, including seven in
the genus Amblyomma, of which only Amblyomma maculatum/Amblyomma triste is known
to be established in the United States. Most ticks on birds (67%) were
neotropical species with ranges in Central and South America. Additionally, a
single Ixodes genus tick was detected. A total of 29% of the ticks (n = 137) and
no avian blood samples (n = 100) were positive for infection with Rickettsia
species, including Rickettsia parkeri, an emerging cause of spotted fever in
humans in the southern United States, a species in the group of Rickettsia
monacensis, and uncharacterized species and endosymbionts of unknown
pathogenicity. No avian tick or blood samples tested positive for B. burgdorferi,
the etiologic agent of Lyme disease. An extrapolation of our findings suggests
that anywhere from 4 to 39 million exotic neotropical ticks are transported to
the United States annually on migratory songbirds, with uncertain consequences
for human and animal health if the current barriers to their establishment and
spread are overcome.
PMID- 26431963
TI - MELK-T1, a small-molecule inhibitor of protein kinase MELK, decreases DNA-damage
tolerance in proliferating cancer cells.
AB - Maternal embryonic leucine zipper kinase (MELK), a serine/threonine protein
kinase, has oncogenic properties and is overexpressed in many cancer cells. The
oncogenic function of MELK is attributed to its capacity to disable critical cell
cycle checkpoints and reduce replication stress. Most functional studies have
relied on the use of siRNA/shRNA-mediated gene silencing. In the present study,
we have explored the biological function of MELK using MELK-T1, a novel and
selective small-molecule inhibitor. Strikingly, MELK-T1 triggered a rapid and
proteasome-dependent degradation of the MELK protein. Treatment of MCF-7
(Michigan Cancer Foundation-7) breast adenocarcinoma cells with MELK-T1 induced
the accumulation of stalled replication forks and double-strand breaks that
culminated in a replicative senescence phenotype. This phenotype correlated with
a rapid and long-lasting ataxia telangiectasia-mutated (ATM) activation and
phosphorylation of checkpoint kinase 2 (CHK2). Furthermore, MELK-T1 induced a
strong phosphorylation of p53 (cellular tumour antigen p53), a prolonged up
regulation of p21 (cyclin-dependent kinase inhibitor 1) and a down-regulation of
FOXM1 (Forkhead Box M1) target genes. Our data indicate that MELK is a key
stimulator of proliferation by its ability to increase the threshold for DNA
damage tolerance (DDT). Thus, targeting MELK by the inhibition of both its
catalytic activity and its protein stability might sensitize tumours to DNA
damaging agents or radiation therapy by lowering the DNA-damage threshold.
PMID- 26431965
TI - Facultative control of matrix production optimizes competitive fitness in
Pseudomonas aeruginosa PA14 biofilm models.
AB - As biofilms grow, resident cells inevitably face the challenge of resource
limitation. In the opportunistic pathogen Pseudomonas aeruginosa PA14, electron
acceptor availability affects matrix production and, as a result, biofilm
morphogenesis. The secreted matrix polysaccharide Pel is required for pellicle
formation and for colony wrinkling, two activities that promote access to O2. We
examined the exploitability and evolvability of Pel production at the air-liquid
interface (during pellicle formation) and on solid surfaces (during colony
formation). Although Pel contributes to the developmental response to electron
acceptor limitation in both biofilm formation regimes, we found variation in the
exploitability of its production and necessity for competitive fitness between
the two systems. The wild type showed a competitive advantage against a non-Pel
producing mutant in pellicles but no advantage in colonies. Adaptation to the
pellicle environment selected for mutants with a competitive advantage against
the wild type in pellicles but also caused a severe disadvantage in colonies,
even in wrinkled colony centers. Evolution in the colony center produced
divergent phenotypes, while adaptation to the colony edge produced mutants with
clear competitive advantages against the wild type in this O2-replete niche. In
general, the structurally heterogeneous colony environment promoted more
diversification than the more homogeneous pellicle. These results suggest that
the role of Pel in community structure formation in response to electron acceptor
limitation is unique to specific biofilm models and that the facultative control
of Pel production is required for PA14 to maintain optimum benefit in different
types of communities.
PMID- 26431966
TI - Two pathways for glutamate biosynthesis in the syntrophic bacterium Syntrophus
aciditrophicus.
AB - The anaerobic metabolism of crotonate, benzoate, and cyclohexane carboxylate by
Syntrophus aciditrophicus grown syntrophically with Methanospirillum hungatei
provides a model to study syntrophic cooperation. Recent studies revealed that S.
aciditrophicus contains Re-citrate synthase but lacks the common Si-citrate
synthase. To establish whether the Re-citrate synthase is involved in glutamate
synthesis via the oxidative branch of the Krebs cycle, we have used [1
(13)C]acetate and [1-(14)C]acetate as well as [(13)C]bicarbonate as additional
carbon sources during axenic growth of S. aciditrophicus on crotonate. Our
analyses showed that labeled carbons were detected in at least 14 amino acids,
indicating the global utilization of acetate and bicarbonate. The labeling
patterns of alanine and aspartate verified that pyruvate and oxaloacetate were
synthesized by consecutive carboxylations of acetyl coenzyme A (acetyl-CoA). The
isotopomer profile and (13)C nuclear magnetic resonance (NMR) spectroscopy of the
obtained [(13)C]glutamate, as well as decarboxylation of [(14)C]glutamate,
revealed that this amino acid was synthesized by two pathways. Unexpectedly, only
the minor route used Re-citrate synthase (30 to 40%), whereas the majority of
glutamate was synthesized via the reductive carboxylation of succinate. This
symmetrical intermediate could have been formed from two acetates via hydration
of crotonyl-CoA to 4-hydroxybutyryl-CoA. 4-Hydroxybutyrate was detected in the
medium of S. aciditrophicus when grown on crotonate, but an active hydratase
could not be measured in cell extracts, and the annotated 4-hydroxybutyryl-CoA
dehydratase (SYN_02445) lacks key amino acids needed to catalyze the hydration of
crotonyl-CoA. Besides Clostridium kluyveri, this study reveals the second example
of a microbial species to employ two pathways for glutamate synthesis.
PMID- 26431967
TI - Improvement of glucose uptake rate and production of target chemicals by
overexpressing hexose transporters and transcriptional activator Gcr1 in
Saccharomyces cerevisiae.
AB - Metabolic engineering to increase the glucose uptake rate might be beneficial to
improve microbial production of various fuels and chemicals. In this study, we
enhanced the glucose uptake rate in Saccharomyces cerevisiae by overexpressing
hexose transporters (HXTs). Among the 5 tested HXTs (Hxt1, Hxt2, Hxt3, Hxt4, and
Hxt7), overexpression of high-affinity transporter Hxt7 was the most effective in
increasing the glucose uptake rate, followed by moderate-affinity transporters
Hxt2 and Hxt4. Deletion of STD1 and MTH1, encoding corepressors of HXT genes,
exerted differential effects on the glucose uptake rate, depending on the culture
conditions. In addition, improved cell growth and glucose uptake rates could be
achieved by overexpression of GCR1, which led to increased transcription levels
of HXT1 and ribosomal protein genes. All genetic modifications enhancing the
glucose uptake rate also increased the ethanol production rate in wild-type S.
cerevisiae. Furthermore, the growth-promoting effect of GCR1 overexpression was
successfully applied to lactic acid production in an engineered lactic acid
producing strain, resulting in a significant improvement of productivity and
titers of lactic acid production under acidic fermentation conditions.
PMID- 26431968
TI - Involutin is an Fe3+ reductant secreted by the ectomycorrhizal fungus Paxillus
involutus during Fenton-based decomposition of organic matter.
AB - Ectomycorrhizal fungi play a key role in mobilizing nutrients embedded in
recalcitrant organic matter complexes, thereby increasing nutrient accessibility
to the host plant. Recent studies have shown that during the assimilation of
nutrients, the ectomycorrhizal fungus Paxillus involutus decomposes organic
matter using an oxidative mechanism involving Fenton chemistry (Fe(2+) + H2O2 +
H(+) -> Fe(3+) + OH + H2O), similar to that of brown rot wood-decaying fungi. In
such fungi, secreted metabolites are one of the components that drive one
electron reductions of Fe(3+) and O2, generating Fenton chemistry reagents. Here
we investigated whether such a mechanism is also implemented by P. involutus
during organic matter decomposition. Activity-guided purification was performed
to isolate the Fe(3+)-reducing principle secreted by P. involutus during growth
on a maize compost extract. The Fe(3+)-reducing activity correlated with the
presence of one compound. Mass spectrometry and nuclear magnetic resonance (NMR)
identified this compound as the diarylcyclopentenone involutin. A major part of
the involutin produced by P. involutus during organic matter decomposition was
secreted into the medium, and the metabolite was not detected when the fungus was
grown on a mineral nutrient medium. We also demonstrated that in the presence of
H2O2, involutin has the capacity to drive an in vitro Fenton reaction via Fe(3+)
reduction. Our results show that the mechanism for the reduction of Fe(3+) and
the generation of hydroxyl radicals via Fenton chemistry by ectomycorrhizal fungi
during organic matter decomposition is similar to that employed by the
evolutionarily related brown rot saprotrophs during wood decay.
PMID- 26431969
TI - Interactions between closely related bacterial strains are revealed by deep
transcriptome sequencing.
AB - Comparative genomics, metagenomics, and single-cell technologies have shown that
populations of microbial species encompass assemblages of closely related
strains. This raises the question of whether individual bacterial lineages
respond to the presence of their close relatives by modifying their gene
expression or, instead, whether assemblages simply act as the arithmetic addition
of their individual components. Here, we took advantage of transcriptome
sequencing to address this question. For this, we analyzed the transcriptomes of
two closely related strains of the extremely halophilic bacterium Salinibacter
ruber grown axenically and in coculture. These organisms dominate bacterial
assemblages in hypersaline environments worldwide. The strains used here
cooccurred in the natural environment and are 100% identical in their 16S rRNA
genes, and each strain harbors an accessory genome representing 10% of its
complete genome. Overall, transcriptomic patterns from pure cultures were very
similar for both strains. Expression was detected along practically the whole
genome albeit with some genes at low levels. A subset of genes was very highly
expressed in both strains, including genes coding for the light-driven proton
pump xanthorhodopsin, genes involved in the stress response, and genes coding for
transcriptional regulators. Expression differences between pure cultures affected
mainly genes involved in environmental sensing. When the strains were grown in
coculture, there was a modest but significant change in their individual
transcription patterns compared to those in pure culture. Each strain sensed the
presence of the other and responded in a specific manner, which points to fine
intraspecific transcriptomic modulation.
PMID- 26431970
TI - Multiplexed integrating plasmids for engineering of the erythromycin gene cluster
for expression in Streptomyces spp. and combinatorial biosynthesis.
AB - Bacteria in the genus Streptomyces and its close relatives are prolific producers
of secondary metabolites with antibiotic activity. Genome sequencing of these
bacteria has revealed a rich source of potentially new antibiotic pathways, whose
products have never been observed. Moreover, these new pathways can provide novel
genes that could be used in combinatorial biosynthesis approaches to generate
unnatural analogues of existing antibiotics. We explore here the use of multiple
orthologous integrating plasmid systems, based on the int/attP loci from phages
TG1, SV1, and phiBT1, to express the polyketide synthase (PKS) for erythromycin
in a heterologous Streptomyces host. Streptomyces strains containing the three
polyketide synthase genes eryAI, eryAII, and eryAIII expressed from three
different integrated plasmids produced the aglycone intermediate, 6
deoxyerythronolide B (6-dEB). A further pair of integrating plasmids, both
derived from the phiC31 int/attP locus, were constructed carrying a gene cassette
for glycosylation of the aglycone intermediates, with or without the tailoring
gene, eryF, required for the synthesis of erythronolide B (EB). Liquid
chromatography-mass spectrometry of the metabolites indicated the production of
angolosaminyl-6-dEB and angolosaminyl-EB. The advantages of using multiplexed
integrating plasmids for engineering expression and for combinatorial
biosynthesis were demonstrated.
PMID- 26431971
TI - Landscape position influences microbial composition and function via
redistribution of soil water across a watershed.
AB - Subalpine forest ecosystems influence global carbon cycling. However, little is
known about the compositions of their soil microbial communities and how these
may vary with soil environmental conditions. The goal of this study was to
characterize the soil microbial communities in a subalpine forest watershed in
central Montana (Stringer Creek Watershed within the Tenderfoot Creek
Experimental Forest) and to investigate their relationships with environmental
conditions and soil carbonaceous gases. As assessed by tagged Illumina sequencing
of the 16S rRNA gene, community composition and structure differed significantly
among three landscape positions: high upland zones (HUZ), low upland zones (LUZ),
and riparian zones (RZ). Soil depth effects on phylogenetic diversity and beta
diversity varied across landscape positions, being more evident in RZ than in
HUZ. Mantel tests revealed significant correlations between microbial community
assembly patterns and the soil environmental factors tested (water content,
temperature, oxygen, and pH) and soil carbonaceous gases (carbon dioxide
concentration and efflux and methane concentration). With one exception,
methanogens were detected only in RZ soils. In contrast, methanotrophs were
detected in all three landscape positions. Type I methanotrophs dominated RZ
soils, while type II methanotrophs dominated LUZ and HUZ soils. The relative
abundances of methanotroph populations correlated positively with soil water
content (R = 0.72, P < 0.001) and negatively with soil oxygen (R = -0.53, P =
0.008). Our results suggest the coherence of soil microbial communities within
and differences in communities between landscape positions in a subalpine
forested watershed that reflect historical and contemporary environmental
conditions.
PMID- 26431972
TI - Protein engineering of a nitrilase from Burkholderia cenocepacia J2315 for
efficient and enantioselective production of (R)-o-chloromandelic acid.
AB - The nitrilase-mediated pathway has significant advantages in the production of
optically pure aromatic alpha-hydroxy carboxylic acids. However, low
enantioselectivity and activity are observed on hydrolyzing o
chloromandelonitrile to produce optically pure (R)-o-chloromandelic acid. In the
present study, a protein engineering approach was successfully used to enhance
the performance of nitrilase obtained from Burkholderia cenocepacia strain J2315
(BCJ2315) in hydrolyzing o-chloromandelonitrile. Four hot spots (T49, I113, Y199,
and T310) responsible for the enantioselectivity and activity of BCJ2315 were
identified by random mutagenesis. An effective double mutant (I113M/Y199G
[encoding the replacement of I with M at position 113 and Y with G at position
199]), which demonstrated remarkably enhanced enantioselectivity (99.1%
enantiomeric excess [ee] compared to 89.2% ee for the wild type) and relative
activity (360% of the wild type), was created by two rounds of site saturation
mutagenesis, first at each of the four hot spots and subsequently at position 199
for combination with the selected beneficial mutation I113M. Notably, this mutant
also demonstrated dramatically enhanced enantioselectivity and activity toward
other mandelonitrile derivatives and, thus, broadened the substrate scope of this
nitrilase. Using an ethyl acetate-water (1:9) biphasic system, o
chloromandelonitrile (500 mM) was completely hydrolyzed in 3 h by this mutant
with a small amount of biocatalyst (10 g/liter wet cells), resulting in a high
concentration of (R)-o-chloromandelic acid with 98.7% ee, to our knowledge the
highest ever reported. This result highlights a promising method for industrial
production of optically pure (R)-o-chloromandelic acid. Insight into the source
of enantioselectivity and activity was gained by homology modeling and molecular
docking experiments.
PMID- 26431973
TI - Adaptation of the cecal bacterial microbiome of growing pigs in response to
resistant starch type 4.
AB - Resistant starch (RS) exacerbates health benefits on the host via modulation of
the gut bacterial community. By far, these effects have been less well explored
for RS of type 4. This study aimed at gaining a community-wide insight into the
impact of enzymatically modified starch (EMS) on the cecal microbiota and hindgut
fermentation in growing pigs. Castrated male pigs (n = 12/diet; 29-kg body
weight) were fed diets with either 70% EMS or control starch for 10 days. The
bacterial profile of each cecal sample was determined by sequencing of the V345
region of the 16S rRNA gene using the Illumina MiSeq platform. EMS diet reduced
short-chain fatty acid concentrations in cecum and proximal colon compared to the
control diet. Linear discriminant analyses and K means clustering indicated diet
specific cecal community profiles, whereby diversity and species richness were
not different among diets. Pigs showed host-specific variation in their most
abundant phyla, Firmicutes (55%), Proteobacteria (35%), and Bacteroidetes (10%).
The EMS diet decreased abundance of Ruminococcus, Parasutterella, Bilophila,
Enterococcus, and Lactobacillus operational taxonomic units (OTU), whereas
Meniscus and Actinobacillus OTU were increased compared to those with the control
diet (P < 0.05). Quantitative PCR confirmed results for host effect on
Enterobacteriaceae and diet effect on members of the Lactobacillus group. The
presence of less cecal short-chain fatty acids and the imputed metabolic
functions of the cecal microbiome suggested that EMS was less degradable for
cecal bacteria than the control starch. The present EMS effects on the bacterial
community profiles were different than the previously reported RS effects and can
be linked to the chemical structure of EMS.
PMID- 26431974
TI - Microbiological oxidation of antimony(III) with oxygen or nitrate by bacteria
isolated from contaminated mine sediments.
AB - Bacterial oxidation of arsenite [As(III)] is a well-studied and important
biogeochemical pathway that directly influences the mobility and toxicity of
arsenic in the environment. In contrast, little is known about microbiological
oxidation of the chemically similar anion antimonite [Sb(III)]. In this study,
two bacterial strains, designated IDSBO-1 and IDSBO-4, which grow on tartrate
compounds and oxidize Sb(III) using either oxygen or nitrate, respectively, as a
terminal electron acceptor, were isolated from contaminated mine sediments. Both
isolates belonged to the Comamonadaceae family and were 99% similar to previously
described species. We identify these novel strains as Hydrogenophaga
taeniospiralis strain IDSBO-1 and Variovorax paradoxus strain IDSBO-4. Both
strains possess a gene with homology to the aioA gene, which encodes an As(III)
oxidase, and both oxidize As(III) aerobically, but only IDSBO-4 oxidized Sb(III)
in the presence of air, while strain IDSBO-1 could achieve this via nitrate
respiration. Our results suggest that expression of aioA is not induced by
Sb(III) but may be involved in Sb(III) oxidation along with an Sb(III)-specific
pathway. Phylogenetic analysis of proteins encoded by the aioA genes revealed a
close sequence similarity (90%) among the two isolates and other known As(III)
oxidizing bacteria, particularly Acidovorax sp. strain NO1. Both isolates were
capable of chemolithoautotrophic growth using As(III) as a primary electron
donor, and strain IDSBO-4 exhibited incorporation of radiolabeled
[(14)C]bicarbonate while oxidizing Sb(III) from Sb(III)-tartrate, suggesting
possible Sb(III)-dependent autotrophy. Enrichment cultures produced the Sb(V)
oxide mineral mopungite and lesser amounts of Sb(III)-bearing senarmontite as
precipitates.
PMID- 26431976
TI - Characterization of mesenchymal stem cells in sheep naturally infected with
scrapie.
AB - Mesenchymal stem cells (MSCs) can be infected with prions and have been proposed
as in vitro cell-based models for prion replication. In addition, autologous MSCs
are of interest for cell therapy in neurodegenerative diseases. To the best of
our knowledge, the effect of prion diseases on the characteristics of these cells
has never been investigated. Here, we analysed the properties of MSCs obtained
from bone marrow (BM-MSCs) and peripheral blood (PB-MSCs) of sheep naturally
infected with scrapie - a large mammal model for the study of prion diseases.
After three passages of expansion, MSCs derived from scrapie animals displayed
similar adipogenic, chondrogenic and osteogenic differentiation ability as cells
from healthy controls, although a subtle decrease in the proliferation potential
was observed. Exceptionally, mesenchymal markers such as CD29 were significantly
upregulated at the transcript level compared with controls. Scrapie MSCs were
able to transdifferentiate into neuron-like cells, but displayed lower levels of
neurogenic markers at basal conditions, which could limit this potential .The
expression levels of cellular prion protein (PrPC) were highly variable between
cultures, and no significant differences were observed between control and
scrapie-derived MSCs. However, during neurogenic differentiation the expression
of PrPC was upregulated in MSCs. This characteristic could be useful for
developing in vitro models for prion replication. Despite the infectivity
reported for MSCs obtained from scrapie-infected mice and Creutzfeldt-Jakob
disease patients, protein misfolding cyclic amplification did not detect PrPSc in
BM- or PB-MSCs from scrapie-infected sheep, which limits their use for in vivo
diagnosis for scrapie.
PMID- 26431975
TI - Metabolic response of Clostridium ljungdahlii to oxygen exposure.
AB - Clostridium ljungdahlii is an important synthesis gas-fermenting bacterium used
in the biofuels industry, and a preliminary investigation showed that it has some
tolerance to oxygen when cultured in rich mixotrophic medium. Batch cultures not
only continue to grow and consume H2, CO, and fructose after 8% O2 exposure, but
fermentation product analysis revealed an increase in ethanol concentration and
decreased acetate concentration compared to non-oxygen-exposed cultures. In this
study, the mechanisms for higher ethanol production and oxygen/reactive oxygen
species (ROS) detoxification were identified using a combination of fermentation,
transcriptome sequencing (RNA-seq) differential expression, and enzyme activity
analyses. The results indicate that the higher ethanol and lower acetate
concentrations were due to the carboxylic acid reductase activity of a more
highly expressed predicted aldehyde oxidoreductase (CLJU_c24130) and that C.
ljungdahlii's primary defense upon oxygen exposure is a predicted rubrerythrin
(CLJU_c39340). The metabolic responses of higher ethanol production and
oxygen/ROS detoxification were found to be linked by cofactor management and
substrate and energy metabolism. This study contributes new insights into the
physiology and metabolism of C. ljungdahlii and provides new genetic targets to
generate C. ljungdahlii strains that produce more ethanol and are more tolerant
to syngas contaminants.
PMID- 26431979
TI - Preface.
PMID- 26431977
TI - Photodynamic antimicrobial chemotherapy and ultraconservative caries removal
linked for management of deep caries lesions.
AB - BACKGROUND: Ultraconservative removal of carious tissue is becoming increasingly
highlighted for management of deep caries lesions, and combined with an
antimicrobial photochemistry-based treatment modality (PACT), this approach can
be enhanced favoring dental tissue repair and preservation. The aim was to
investigate the effectiveness of PACT using a light emitting diode (LED)
associated with a photosensitizer toluidine blue ortho (TBO) on deep caries
lesions. METHODS: For that, a single blind, randomized, controlled, split-mouth
clinical trial where 45 patients with at least two deep carious lesions on
permanent posterior teeth was performed. The primary intervention was deep caries
lesion management with disinfection of remaining dentin tissue using PACT.
Bacterial counts were measured following treatments as the main outcome. The
remaining dentinal samples of each lesion were treated with either non-PACT
control or PACT. The PACT procedure were characterized by 100 MUg mL(-1) TBO
followed by 94J cm(-2) LED irradiation. Samples of dentin were collected before
and immediately after treatments for microbiological analysis of total viable
bacteria, mutans streptococci and Lactobacillus spp. counts. Microbial reduction
was data were submitted to unpaired t test (alpha=5%). RESULTS: PACT led to
statistically significant reductions in mutans streptococci (1.08 +/- 1.20 log),
Lactobacillus spp. (1.69 +/- 1.37 log), and total viable bacteria (1.07 +/- 1.01
log) compared to the control, which showed log reductions respectively of 0.05 +/
0.49, 0.52 +/- 0.89, and 0.47 +/- 0.77 for the same microorganisms. CONCLUSION:
Dentin from deep carious lesions treated with PACT showed a decrease in
cariogenic microbial load.
PMID- 26431980
TI - CT and D-dimer testing are overused in patients with suspected pulmonary
embolism, US college says.
PMID- 26431981
TI - Impact of quadrivalent human papillomavirus vaccine in women at increased risk of
genital warts burden: Population-based cross-sectional survey of Czech women aged
16 to 40 years.
AB - BACKGROUND: To assess the impact of a quadrivalent human papillomavirus vaccine
(4HPV) in women at increased risk of genital warts (GWs) acquisition. METHODS:
The study was conducted using a population-based cross-sectional survey of 19,199
women aged 16 to 40 years randomly chosen from the general population in the
Czech Republic between January 2013 and March 2014. A total of 1086 women
reported having received the 4HPV vaccine. The vaccine's effectiveness was
estimated not only in the general population of women but also in those at
increased risk due to having a sexual partner with GWs or prior GWs history.
RESULTS: The acquisition of GWs was dramatically reduced by 90.6% (80.1-95.6%) in
immunised women at least one year after the completion of the 4HPV vaccination in
comparison with unimmunised women. Recurrent GWs prevalences of 1.1% (95% CI, 0.0
5.9) and 10.9% (95% CI, 9.1-12.9) in immunised and unimmunised women with prior
GWs history, respectively, resulted in a vaccine effectiveness of 89.0% (38.6
98.0%). The notably strong protective effect of 4HPV immunisation in women who
had a sexual partner with GWs was demonstrated by a very low age-adjusted odds
ratio of 0.02 (95% CI 0.01-0.10) in contrast to unimmunised women. CONCLUSIONS:
To lower the chance of genital warts acquisition in the general population and in
populations at increased risk, only current 4HPV or incoming 9HPV vaccination
should be recommended to provide effective protection.
PMID- 26431978
TI - Bone disease in cystic fibrosis: new pathogenic insights opening novel therapies.
AB - Mutations within the gene encoding for the chloride ion channel cystic fibrosis
transmembrane conductance regulator (CFTR) results in cystic fibrosis (CF), the
most common lethal autosomal recessive genetic disease that causes a number of
long-term health problems, as the bone disease. Osteoporosis and increased
vertebral fracture risk associated with CF disease are becoming more important as
the life expectancy of patients continues to improve. The etiology of low bone
density is multifactorial, most probably a combination of inadequate peak bone
mass during puberty and increased bone losses in adults. Body mass index, male
sex, advanced pulmonary disease, malnutrition and chronic therapies are
established additional risk factors for CF-related bone disease (CFBD).
Consistently, recent evidence has confirmed that CFTR plays a major role in the
osteoprotegerin (OPG) and COX-2 metabolite prostaglandin E2 (PGE2) production,
two key regulators in the bone formation and regeneration. Several others
mechanisms were also recognized from animal and cell models contributing to
malfunctions of osteoblast (cell that form bone) and indirectly of bone
resorpting osteoclasts. Understanding such mechanisms is crucial for the
development of therapies in CFBD. Innovative therapeutic approaches using CFTR
modulators such as C18 have recently shown in vitro capacity to enhance PGE2
production and normalized the RANKL-to-OPG ratio in human osteoblasts bearing the
mutation F508del-CFTR and therefore potential clinical utility in CFBD. This
review focuses on the recently identified pathogenic mechanisms leading to CFBD
and potential future therapies for treating CFBD.
PMID- 26431982
TI - RTS,S: Toward a first landmark on the Malaria Vaccine Technology Roadmap.
AB - The Malaria Vaccine Technology Roadmap calls for a 2015 landmark goal of a first
generation malaria vaccine that has protective efficacy against severe disease
and death, lasting longer than one year. This review focuses on product
development efforts over the last five years of RTS,S, a pre-erythrocytic,
recombinant subunit, adjuvanted, candidate malaria vaccine designed with this
goal of a first-generation malaria vaccine in mind. RTS,S recently completed a
successful pivotal Phase III safety, efficacy and immunogenicity study. Although
vaccine efficacy was found to be modest, a substantial number of cases of
clinical malaria were averted over a 3-4 years period, particularly in settings
of significant disease burden. European regulators have subsequently adopted a
positive opinion under the Article 58 procedure for an indication of active
immunization of children aged 6 weeks up to 17 months against malaria caused by
Plasmodium falciparum and against hepatitis B. Further evaluations of the
benefit, risk, feasibility and cost-effectiveness of RTS,S are now anticipated
through policy and financing reviews at the global and national levels.
PMID- 26431983
TI - Immunogenicity and safety of the new intradermal influenza vaccine in adults and
elderly: A randomized phase 1/2 clinical trial.
AB - BACKGROUND: Recent clinical evidence indicates that an intradermal (ID) delivery
of vaccines confers superior immunogenicity as compared to a standard
intramuscular or subcutaneous (SC) delivery. METHODS: In this exploratory study,
600 healthy adults were randomized to 6 study groups with subgroups of young
adults (20-64 years old) and older adults (65 years and older). The subjects were
either injected by a novel ID injection system with a single dose of 6, 9, or 15
MUg HA or two doses (21 days apart) of 15 MUg HA per strain or injected by an SC
injection method with a single or two doses (21 days apart) of 15 MUg HA per
strain. Immunogenicity was assessed using hemagglutination inhibition (HAI) titer
and microneutralization titer on Days 0, 10, 21, and 42. Solicited and
unsolicited adverse events were recorded for 7 and 21 days post-vaccination,
respectively. RESULTS: In both young adults and older adults groups, the
geometric titer (GMT) ratios of HAI in the ID 15 MUg HA group were higher than
those in the SC 15 MUg HA group on both Day 10 and Day 21, while those in the ID
6 and ID 9 MUg HA groups were comparable with those in the SC 15 MUg HA group.
The kinetics of GMTs of HAI suggested that the ID vaccine has the potential to
induce the prompt immune response, which is rather hampered in older adults as
seen in the SC vaccine groups. The injection-site AEs were generally mild and
transient, and did not occur in a dose or dosage-dependent manner. CONCLUSIONS:
The results of this study clearly suggest that the immunologic profile of the ID
vaccine is better than that of the SC vaccine, while the safety profile of the ID
vaccine is similar to that of the SC vaccine. In this exploratory study with
almost 100 subjects per each group, single or two-dose administration of the ID
vaccine containing 15 MUg HA was suggested to be an appropriate regimen in order
to prevent influenza and to reduce the associated disease burden. TRIAL
REGISTRATION: JAPIC Clinical Trials Information (JapicCTI-132096).
PMID- 26431984
TI - HPV vaccination series completion and co-vaccination: Pairing vaccines may matter
for adolescents.
AB - Very little is known about the effect of concurrent co-vaccination on HPV series
completion. This study utilized a retrospective review of a Clinical Data
Repository to assess whether concurrent vaccination had an impact on HPV
vaccination series completion, and whether there were differences based on age.
3371 patients who received the HPV vaccine at a single academic medical center
between the years 2009-2013 were included in this analysis. The adjusted odds
ratio (aOR) for effect of concurrent vaccination on series completion for the age
group 9-18 was 1.32 (95% CI 1.09, 1.60). Although not statistically significant,
the aOR for effect of concurrent vaccination on completion changed direction for
the 19-25 age group and was 0.44 (95% CI 0.17, 1.12). This study provides
preliminary evidence that pairing the HPV vaccine with one or more co-vaccines
may yield a higher HPV vaccination completion rate among adolescents age 9-18.
PMID- 26431985
TI - Hepatitis B virus infection in northern Uganda: Impact of pentavalent hepatitis B
vaccination.
AB - Chronic hepatitis B virus infection (CHBI) is effectively prevented by
vaccination starting at birth. Beginning in 2002 Uganda adopted a policy of
providing the pentavalent hepatitis B vaccine starting at 6 weeks of age.
However, there is concern that this delay may leave the infant vulnerable to
infection during the first 6 weeks of life. We assessed whether vaccination at 6
weeks was an effective strategy by HBV serologic study. Of 656 persons tested for
HBV, 9.4% were chronically infected; among children aged 5-9 years the prevalence
was 7.6%. Of all tested, 73 were born (i.e., aged <= 4 years) after the
introduction of the pentavalent vaccine; none were infected with HBV (p = 0.003).
In this study, vaccination with the pentavalent vaccine at 6 weeks did not result
in CHBI, but rather provides an opportunity to prevent mother-to-infant
transmission of HBV infection where there is no access to birth-dose vaccine.
PMID- 26431986
TI - Workshop report: Malaria vaccine development in Europe--preparing for the future.
AB - The deployment of a safe and effective malaria vaccine will be an important tool
for the control of malaria and the reduction in malaria deaths. With the launch
of the 2030 Malaria Vaccine Technology Roadmap, the malaria community has updated
the goals and priorities for the development of such a vaccine and is now paving
the way for a second phase of malaria vaccine development. During a workshop in
Brussels in November 2014, hosted by the European Vaccine Initiative, key players
from the European, North American and African malaria vaccine community discussed
European strategies for future malaria vaccine development in the global context.
The recommendations of the European malaria community should guide researchers,
policy makers and funders of global health research and development in fulfilling
the ambitious goals set in the updated Malaria Vaccine Technology Roadmap.
PMID- 26431987
TI - Effect of age on the incidence of aseptic meningitis following immunization with
monovalent mumps vaccine.
AB - OBJECTIVE: The purpose of this study was to determine the risk of aseptic
meningitis after mumps vaccination in younger children compared with older
children. METHODS: This prospective cohort study included a total of 21,465
children under 18 years of age who had received the first dose of three of the
Japanese mumps monovalent vaccine. We compared the cumulative incidence of
aseptic meningitis for 30 days after vaccination among the following age groups:
<= 1, 2, 3-4, and >= 5 years old. We also investigated the cumulative incidence
of salivary gland swelling, a fever (>= 38 degrees C) lasting at least 3 days
during the 10 to 25 days following immunization, vomiting of 3 times or more,
headache, and seizure. RESULTS: A total of 10 aseptic meningitis, 551 salivary
gland swelling, 844 fevers, 669 vomiting, 757 headaches, and 29 seizure cases
were identified. The cumulative incidence of aseptic meningitis increased with
age (0.016%, 0.021%, 0.066%, and 0.096%, respectively). Statistical significance
was observed between children >= 3 years old and those < 3 years of age [0.078%
vs. 0.018%, RR 4.35 (95% CI 1.05-18.2), p=0.04]. The cumulative incidence of
salivary gland swelling also increased with age (1.8%, 3.0%, 3.5%, and 4.5%,
respectively). For non-specific adverse events, the cumulative incidence of fever
or seizure decreased with age. In contrast, the cumulative incidence of headache
increased with age. The cumulative incidence of vomiting was similar among
children <= 4 years of age; however, that in those children >= 5 years old was
significantly lower. CONCLUSIONS: The first dose of mumps vaccine that is
currently available for use in Japan may be administered in children less than 3
years of age in order to complicate a less aseptic meningitis after immunization.
PMID- 26431988
TI - Symposium report of the 17th annual meeting of the Japanese Society for
Vaccinology, 2013: Bacterial vaccines: Effectiveness and issues.
PMID- 26431989
TI - Assessment of a novel recombinant vesicular stomatitis virus with triple
mutations in its matrix protein as a vaccine for pigs.
AB - Vesicular stomatitis virus (VSV) causes a serious vesicular disease responsible
for economic losses in the livestock industry. Currently, there are no suitable
vaccines to prevent VSV infection. Although the structural matrix (M) protein of
VSV has been shown to be a virulence factor in rodent models, its role in the
pathogenicity of VSV infection in livestock species is unknown. We hypothesized
that VSV with mutations in the M protein represents a novel live attenuated
vaccine candidate. To test this, we introduced mutations into VSV M protein using
reverse genetics and assessed their attenuation both in vitro and in pigs, an
important natural host of VSV. A recombinant VSV with a triple amino acid
mutation in M protein (VSVMT) demonstrated a significantly reduced ability to
inhibit the type I interferon (IFN) signaling pathway and to shutoff host gene
expression compared to WT-VSV and a mutant virus with a single amino acid
deletion (VSVDeltaM51). Inoculation of pigs with VSVMT induced no apparent
vesicular lesions but stimulated virus-neutralizing antibodies and animals were
protected against virulent VSV challenge infection. These data demonstrate that
the M protein is an important virulence factor for VSV in swine and VSVMT
represents a novel vaccine candidate for VSV infections in pigs.
PMID- 26431990
TI - Cross-protective efficacy of engineering serotype A foot-and-mouth disease virus
vaccine against the two pandemic strains in swine.
AB - Foot-and-mouth disease (FMD) is a highly contagious vesicular disease that
affects domestic and wild cloven-hoofed animals worldwide. Recently, a series of
outbreaks of type A FMDV occurred in Southeast Asian countries, China, the Russia
Federation, Mongolia, Kazakhstan and South Korea. The FMD virus (A/GDMM/CHA/2013)
from China's Guangdong province (2013) is representative of those responsible for
the latest epidemic, and has low amino acid identity (93.9%) in VP1 protein with
the epidemic strain A/WH/CHA/09 from Wuhan, China in 2009. Both of isolates
belong to the Sea-97 genotype of ASIA topotype. Therefore, the application of a
new vaccine strain with cross-protective efficacy is of fundamental importance to
control the spread of the two described pandemic strains. A chimeric strain rA/P1
FMDV constructed by our lab previously through replacing the P1 gene in the
vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09, has been
demonstrated to exhibit good growth characteristics in culture, and the rA/P1
FMDV inactivated vaccine can provide protection against epidemic strain
A/WH/CHA/09 in cattle. However, it is still unclear whether the vaccine produces
efficient protection against the new pandemic strain (A/GDMM/CHA/2013). Here,
vaccine matching and pig 50% protective dose (PD50) tests were performed to
assess the vaccine potency. The vaccine matching test showed cross-reactivity of
sera from full dose vaccine vaccinated pigs with A/WH/CHA/09 and A/GDMM/CHA/2013
isolates, with average r1 values of 0.94+/-0.12 and 0.68+/-0.06 (r1>=0.3), which
indicates that the rA/P1-FMDV vaccine is likely to confer good cross-protection
against the two isolates. When challenged with two pandemic isolates A/WH/CHA/09
and A/GDMM/CHA/2013 strain, the vaccine achieved 12.51 PD50 and 10.05 PD50 per
dose (2.8MUg), respectively. The results indicated that the rA/P1-FMDV
inactivated vaccine could protect pigs against both A/WH/CHA/09 and
A/GDMM/CHA/2013 pandemic isolates.
PMID- 26431992
TI - Functional hyperspectral imaging captures subtle details of cell metabolism in
olfactory neurosphere cells, disease-specific models of neurodegenerative
disorders.
AB - Hyperspectral imaging uses spectral and spatial image information for target
detection and classification. In this work hyperspectral autofluorescence imaging
was applied to patient olfactory neurosphere-derived cells, a cell model of a
human metabolic disease MELAS (mitochondrial myopathy, encephalomyopathy, lactic
acidosis, stroke-like syndrome). By using an endogenous source of contrast subtle
metabolic variations have been detected between living cells in their full
morphological context which made it possible to distinguish healthy from diseased
cells before and after therapy. Cellular maps of native fluorophores, flavins,
bound and free NADH and retinoids unveiled subtle metabolic signatures and helped
uncover significant cell subpopulations, in particular a subpopulation with
compromised mitochondrial function. Taken together, our results demonstrate that
multispectral spectral imaging provides a new non-invasive method to investigate
neurodegenerative and other disease models, and it paves the way for novel
cellular characterisation in health, disease and during treatment, with proper
account of intrinsic cellular heterogeneity.
PMID- 26431991
TI - MMR vaccination status of children exempted from school-entry immunization
mandates.
AB - BACKGROUND: Child immunizations are one of the most successful public health
interventions of the past century. Still, parental vaccine hesitancy is
widespread and increasing. One manifestation of this are rising rates of
nonmedical or "personal beliefs" exemptions (PBEs) from school-entry immunization
mandates. Exemptions have been shown to be associated with increased risk of
disease outbreak, but the strength of this association depends critically on the
true vaccination status of exempted children, which has not been assessed.
OBJECTIVE: To estimate the true measles-mumps-rubella (MMR) vaccination status of
children with PBEs. METHODS: We use administrative data collected by the
California Department of Public Health in 2009 and imputation to estimate the MMR
vaccination status of children with PBEs under varying scenarios. RESULTS:
Results from 2009 surveillance data indicate MMR1/MMR2 coverage of 18-47% among
children with PBEs at typical schools and 11-34% among children with PBEs at
schools with high PBE rates. Imputation scenarios point to much higher coverage
(64-92% for MMR1 and 25-58% for MMR2 at typical schools; 49-90% for MMR1 and 16
63% for MMR2 at high PBE schools) but still below levels needed to maintain herd
immunity against measles. CONCLUSIONS: These coverage estimates suggest that
prior analyses of the relative risk of measles associated with vaccine refusal
underestimate that risk by an order of magnitude of 2-10 times.
PMID- 26431993
TI - The impact of cognitive load on reward evaluation.
AB - The neural systems that afford our ability to evaluate rewards and punishments
are impacted by a variety of external factors. Here, we demonstrate that
increased cognitive load reduces the functional efficacy of a reward processing
system within the human medial-frontal cortex. In our paradigm, two groups of
participants used performance feedback to estimate the exact duration of one
second while electroencephalographic (EEG) data was recorded. Prior to performing
the time estimation task, both groups were instructed to keep their eyes still
and avoid blinking in line with well established EEG protocol. However, during
performance of the time-estimation task, one of the two groups was provided with
trial-to-trial-feedback about their performance on the time-estimation task and
their eye movements to induce a higher level of cognitive load relative to
participants in the other group who were solely provided with feedback about the
accuracy of their temporal estimates. In line with previous work, we found that
the higher level of cognitive load reduced the amplitude of the feedback-related
negativity, a component of the human event-related brain potential associated
with reward evaluation within the medial-frontal cortex. Importantly, our results
provide further support that increased cognitive load reduces the functional
efficacy of a neural system associated with reward processing.
PMID- 26431994
TI - Microcirculatory alterations during continuous renal replacement therapy in ICU:
A novel view on the 'dialysis trauma' concept.
AB - OBJECTIVE: The purpose of this study was to evaluate microcirculation over 24 h
renal replacement therapy (CRRT) in critically ill patients. METHODS: We
conducted a single-center, prospective, observational study, measuring
microcirculation parameters, monitored by near infrared spectroscopy (NIRS)
before hemodiafiltration onset (H0), and at six (H6) and 24 h (H24) during CRRT
in critically ill patients. Serum Cystatin C (sCysC) and soluble (s)E-selectin
levels were measured at the same time points. Twenty-eight patients [19 men
(68%)] were included in the study. RESULTS: Tissue oxygen saturation (StO2, %)
[76.5 +/- 12.5 (H0) vs 75 +/- 11 (H6) vs 70 +/- 16 (H24), p = 0.04], reperfusion
rate, indicating endothelial function (EF, %/sec) [2.25 +/- 1.44 (H0) vs 2.1 +/-
1.8 (H6) vs 1.6 +/- 1.4 (H24), p = 0.02] and sCysC (mg/L) [2.7 +/- 0.8 (H0) vs
2.2 +/- 0.6 (H6) vs 1.8 +/- 0.8 (H24), p < 0.0001] significantly decreased within
the 24 h CRRT. Change of EF positively correlated with changes of sCysC within 24
h CRRT (r = 0.464, p = 0.013) while in patients with diabetes the change of StO2
correlated with dose (r = - 0.8, p = 0.01). No correlation existed between
hemoglobin and temperature changes with the deteriorated microcirculation
indices. sE-Selectin levels in serum were elevated; no difference was established
over the 24 h CRRT period. A strong correlation existed between the sE-Selectin
concentration change at H6 and H24 and the mean arterial pressure change in the
same period (r = 0.77, p < 0.001). CONCLUSIONS: During the first 24 h of CRRT
implementation in critically ill patients, deterioration of microcirculation
parameters was noted. Microcirculatory alterations correlated with sCysC changes
and with dose in patients with diabetes.
PMID- 26431995
TI - Clear cell ependymoma with late leptomeningeal and supratentorial metastases.
PMID- 26431996
TI - Multiple posttraumatic cervical pseudomeningoceles.
PMID- 26431997
TI - Association between compensation status and outcomes in spine surgery: a meta
analysis of 31 studies.
AB - BACKGROUND CONTEXT: Numerous studies have demonstrated poorer outcomes in
patients with Workers' compensation (WC) when compared with those without WC
following treatment of various of health conditions, including spine disorders.
It is thus important to consider compensation status when assessing treatment
outcomes in spine surgery. However, reported strengths of association have varied
significantly (1.31-7.22). PURPOSE: The objective of this study was to evaluate
the association of unsatisfactory outcomes on compensation status in spine
surgery patients. STUDY DESIGN/SETTING: A meta-analysis was performed. PATIENT
SAMPLE: Patient sample is not applicable in this study. OUTCOME MEASURE:
Demographics, type of surgery, country, follow-up time, patient satisfaction,
return to work and non-union events were the outcome measures. METHODS: Both
prospective and retrospective studies that compared outcomes between compensated
and non-compensated patients in spine surgery were included. Two independent
investigators extracted outcome data. The meta-analysis was performed using
Revman software. Random effects model was used to calculate risk ratio (RR, 95%
confidence interval [CI]) for dichotomous variables. RESULTS: Thirty-one studies
(13 prospective; 18 retrospective) with a total of 3,567 patients were included
in the analysis. Follow-up time varied from 4 months to 10 years. Twelve studies
involved only decompression; the rest were fusion. Overall RR of an
unsatisfactory outcome was 2.12 [1.74, 2.58; p<.001] in patients with WC when
compared with those without WC after surgery. The RR of an unsatisfactory outcome
in patients with WC, compared with those without, was 2.09 [1.38, 3.17]; p<.01
among studies from Europe and Australia, and 2.14 [1.48, 2.60]; p<.01 among US
studies. The RR of decompression-only procedures was 2.53 [1.85, 3.47]; p<.01,and
1.79 [1.45, 2.21]; p<.01 for fusion. Forty-three percent (209 of 491) of patients
with WC did not return to work versus 17% (214 of 1250) of those without WC (RR
2.07 [1.43, 2.98]; p<.001). Twenty-five percent (74 of 292) and 13.5% (39 of 287)
of patients had non-union in the compensated and non-compensated groups,
respectively. This was not statistically significant (RR 1.33 [0.92, 1.91];
p=.07). CONCLUSIONS: Workers' compensation patients have a two-fold increased
risk of an unsatisfactory outcome compared with non-compensated patients after
surgery. This association was consistent when studies were grouped by country or
procedure. Compensation status must be considered in all surgical intervention
studies.
PMID- 26431998
TI - Identification, classification, and expression profiles of heat shock
transcription factors in tea plant (Camellia sinensis) under temperature stress.
AB - In vascular plants, heat shock transcription factors (Hsfs) regulate heat stress
response by regulating the expression of heat shock proteins. This study
systematically and comprehensively analyzed the Hsf family in tea plant [Camellia
sinensis (L.) O. Kuntze]. A total of 16 CsHsfs were identified from the
transcriptome database of tea plant and analyzed for their phylogenetic
relationships, motifs, and physicochemical characteristics. On the basis of the
phylogenetic comparison of tea plant with Arabidopsis thaliana, Populus
trichocarpa, Theobroma cacao, and Oryza sativa, the CsHsfs were classified into
three classes, namely, A (56.25%), B (37.50%), and C (6.25%). Heat mapping showed
that the expression profiles of CsHsf genes under non-stress conditions varied
among four tea plant cultivars, namely, 'Yunnanshilixiang', 'Chawansanhao',
'Ruchengmaoyecha', and 'Anjibaicha'. Six CsHsf genes (CsHsfA1a, CsHsfA1b,
CsHsfA6, CsHsfB1, CsHsfB2b, and CsHsfC1) were selected from classes A, B, and C
to analyze the expression profiles of CsHsf genes through quantitative real-time
PCR in 'Yingshuang', 'Anjibaicha', and 'Yunnanshilixiang' under high (38 degrees
C) or low (4 degrees C) temperature stress. Temperature stress positively or
negatively regulated all of the selected CsHsf genes, and the expression levels
evidently varied even among CsHsf genes belonging to the same class. This study
provided a relatively detailed summary of Hsfs in tea plant and may serve as a
reference for further studies on the mechanism of temperature stress regulation
by CsHsfs.
PMID- 26431999
TI - Detection of genetic diversity and selection at the coding region of the
melanocortin receptor 1 (MC1R) gene in Tibetan pigs and Landrace pigs.
AB - Domestication and subsequent selective pressures have produced a large variety of
pig coat colors in different regions and breeds. The melanocortin 1 receptor
(MC1R) gene plays a crucial role in determining coat color of mammals. Here, we
investigated genetic diversity and selection at the coding region of the porcine
melanocortin receptor 1 (MC1R) in Tibetan pigs and Landrace pigs. By contrast,
genetic variability was much lower in Landrace pigs than in Tibetan pigs.
Meanwhile, haplotype analysis showed that Tibetan pigs possessed shared
haplotypes, suggesting a possibility of recent introgression event by way of
crossbreeding with neighboring domestic pigs or shared ancestral polymorphism.
Additionally, we detected positive selection at the MC1R in both Tibetan pigs and
Landrace pigs through the dN/dS analysis. These findings suggested that novel
phenotypic change (dark coat color) caused by novel mutations may help Tibetan
pigs against intensive solar ultraviolet (UV) radiation and camouflage in wild
environment, whereas white coat color in Landrace were intentionally selected by
human after domestication. Furthermore, both the phylogenetic analysis and the
network analysis provided clues that MC1R in Asian and European wild boars may
have initially experienced different selective pressures, and MC1R alleles
diversified in modern domesticated pigs.
PMID- 26432000
TI - Prediction of sumoylation sites in proteins using linear discriminant analysis.
AB - Sumoylation is a multifunctional post-translation modification (PTM) in proteins
by the small ubiquitin-related modifiers (SUMOs), which have relations to
ubiquitin in molecular structure. Sumoylation has been found to be involved in
some cellular processes. It is very significant to identify the exact sumoylation
sites in proteins for not only basic researches but also drug developments.
Comparing with time exhausting experiment methods, it is highly desired to
develop computational methods for prediction of sumoylation sites as a complement
to experiment in the post-genomic age. In this work, three feature constructions
(AAIndex, position-specific amino acid propensity and modification of composition
of k-space amino acid pairs) and five different combinations of them were used to
construct features. At last, 178 features were selected as the optimal features
according to the Mathew's correlation coefficient values in 10-fold cross
validation based on linear discriminant analysis. In 10-fold cross-validation on
the benchmark dataset, the accuracy and Mathew's correlation coefficient were
86.92% and 0.6845. Comparing with those existing predictors, SUMO_LDA showed its
better performance.
PMID- 26432001
TI - Overexpression of SOS genes in ciprofloxacin resistant Escherichia coli mutants.
AB - INTRODUCTION: Fluoroquinolones are important antibiotics for the treatment of
urinary tract infections caused by Escherichia coli. Mutational studies have
shown that ciprofloxacin, a member of fluoroquinolones induces SOS response and
mutagenesis in pathogenic bacteria which in turn develop antibiotic resistance.
However, inhibition of SOS response can increase recombination activity which in
turn leads to genetic variation. OBJECTIVE: The aim of this study was to measure
5 SOS genes expressions in nine E. coli mutants with different MICs for
ciprofloxacin following exposure to ciprofloxacin. METHODS: Gene expression was
assessed by quantitative real time PCR. Gene alteration assessment was conducted
by PCR amplification and DNA sequencing. RESULTS: Results showed that the
expression of recA was increased in 5 mutants. This overexpression is not related
to gene alteration, and enhances the expression of polB and umuCD genes encoding
nonmutagenic and mutagenic polymerases, respectively. The direct relationship
between the level of SOS expression and the level of resistance to ciprofloxacin
was also indicated. CONCLUSION: It was concluded that novel therapeutic strategy
that inhibits RecA activity would enhance the efficiency of common antibiotics
against pathogenic bacteria.
PMID- 26432002
TI - A comparison of virus genome sequences with their host silkworm, Bombyx mori.
AB - With the recent availability of the genomes of many viruses and the silkworm,
Bombyx mori, as well as a variety of Basic Local Alignment Search Tool (BLAST)
programs, a new opportunity to gain insight into the interaction of viruses with
the silkworm is possible. This study aims to determine the possible existence of
sequence identities between the genomes of viruses and the silkworm and attempts
to explain this phenomenon. BLAST searches of the genomes of viruses against the
silkworm genome were performed using the resources of the National Center for
Biotechnology Information. All studied viruses contained variable numbers of
short regions with sequence identity to the genome of the silkworm. The short
regions of sequence identity in the genome of the silkworm may be derived from
the genomes of viruses in the long history of silkworm-virus interaction. This
study is the first to compare these genomes, and may contribute to research on
the interaction between viruses and the silkworm.
PMID- 26432003
TI - Lysosomal localization of Japanese medaka (Oryzias latipes) Neu1 sialidase and
its highly conserved enzymatic profiles with human.
AB - Desialylation in the lysosome is a crucial step for glycoprotein degradation. The
abnormality of lysosomal desialylation by NEU1 sialidase is involved in diseases
of mammals such as sialidosis and galactosialidosis. Mammalian Neu1 sialidase is
also localized at plasma membrane where it regulates several signaling pathways
through glycoprotein desialylation. In fish, on the other hand, the mechanism of
desialylation in the lysosome and functions of Neu1 sialidase are still unclear.
Here, to understand the significance of fish Neu1 sialidase, neu1 gene was cloned
from medaka brain and the profiles of its polypeptides were analyzed. Open
reading frame of medaka neu1 consisted 1,182 bp and the similarity of its deduced
amino acids with human NEU1 was 57%. As this recombinant polypeptide did not show
significant sialidase activity, medaka cathepsin A, known in mammals as
protective protein activating Neu1, was cloned and then co-expressed with medaka
Neu1 to examine whether medaka cathepsin A activates Neu1 activity. As a result,
Neu1/cathepsin A showed a drastic increase of sialidase activity toward MU-NANA.
Major substrate of medaka Neu1 was 3-sialyllactose and its optimal pH was 4.0.
With immunofluorescence analysis, signal of overexpressed medaka Neu1 was found
to coincide with Lysotracker signals (organelle marker of lysosome) and co
localized with medaka cathepsin A in fish hepatic Hepa-T1 cells. Furthermore,
part of medaka Neu1 was also detected at plasma membrane. Medaka Neu1 possessed
signal peptide sequence at N-terminal and incomplete lysosomal targeting sequence
at C-terminus. Medaka neu1 gene was ubiquitously expressed in various medaka
tissues, and its expression level was significantly higher than other sialidase
genes such as neu3a, neu3b and neu4. The present study revealed the profiles of
fish Neu1 sialidase and indicated its high conservation with human NEU1 for the
first time, suggesting the presence of similar desialylation system in the medaka
lysosome to human. Moreover, the present study showed the possibility of medaka
as a model animal of human NEU1 sialidase.
PMID- 26432004
TI - Genetic analysis of 15 mtDNA SNP loci in Chinese Yi ethnic group using SNaPshot
minisequencing.
AB - SNaPshot minisequencing is a rapid and robust methodology based on a single base
extension with a labeled ddNTP. The present study detected 15 selected SNPs in
the mitochondrial DNA (mtDNA) control and coding regions by minisequencing
methodology using SNaPshot for forensic purpose. The samples were collected from
99 unrelated individuals of the Yi ethnic minority group in Yunnan Province. We
have predominantly found high-frequency transitions (91.7%) and a significantly
lower frequency of transversions (8.3%). The nt152, 489, 8701, 10,398, 16,183,
and 16,362 loci were highly polymorphic, while the nt231, 473 and 581 loci were
not polymorphic in the studied population. Based on these 15 SNPs, a total of 28
mtDNA haplotypes were defined in 99 individuals with the haplotype diversity of
0.9136. Also, we compared the mtDNA sequences of Yi group and other 9 populations
worldwide and drew a Neighbor-Joining tree based on the shared 12 mtDNA SNP loci,
which demonstrated a close relationship between Yi and Bai groups. In conclusion,
the analysis of the 15 selected SNPs increases considerably the discrimination
power of mtDNA. Moreover, the SNaPshot minisequencing method could quickly detect
mtDNA SNPs, and is economical and sensitive. The set of selected 15 SNPs is
highly informative and is capable for anthropology genetic analysis.
PMID- 26432005
TI - HMGCR positively regulated the growth and migration of glioblastoma cells.
AB - The metabolic program of cancer cells is significant different from the normal
cells, which makes it possible to develop novel strategies targeting cancer
cells. Mevalonate pathway and its rate-limiting enzyme HMG-CoA reductase (HMGCR)
have shown important roles in the progression of several cancer types. However,
their roles in glioblastoma cells remain unknown. In this study, up-regulation of
HMGCR in the clinical glioblastoma samples was observed. Forced expression of
HMGCR promoted the growth and migration of U251 and U373 cells, while knocking
down the expression of HMGCR inhibited the growth, migration and metastasis of
glioblastoma cells. Molecular mechanism studies revealed that HMGCR positively
regulated the expression of TAZ, an important mediator of Hippo pathway, and the
downstream target gene connective tissue growth factor (CTGF), suggesting HMGCR
might activate Hippo pathway in glioblastoma cells. Taken together, our study
demonstrated the oncogenic roles of HMGCR in glioblastoma cells and HMGCR might
be a promising therapeutic target.
PMID- 26432006
TI - Molecular modeling, mutational analysis and conformational switching in IL27: An
in silico structural insight towards AIDS research.
AB - The advancement in proteomics and bioinformatics provokes to discern the
molecular-level probe for HIV inhibitor; human interleukin-27 (IL27).
Documentation documents that tyrosine residues in IL27 play a pivotal role for
interacting with HIV, causing apoptosis of the HIV+ cells. Primarily, 3D
structure of human wild-type (WT) IL27 was built through manifold molecular
modeling techniques after the satisfaction of stereo-chemical properties. Its
essential tyrosine residues were identified. Two mutant models for IL27 were
prepared following the similar protocol by first substituting the tyrosine
residues with glycine (MT_G) and then with alanine (MT_A) in the WT protein.
Molecular dynamics (MD) simulation was performed to obtain a stable conformation.
Conformational alterations in WT, MT_G and MT_A (before and after MD simulation)
disclosed that MT_A was the steadiest one with the best secondary structure
conformation supported by statistical significances. Though huge RMSD variations
were observed on superimposing the MT structures on WT individually, the MTs were
examined to share similar SCOP/CATH fold with TM-score=0.8, indicating that they
retained their functionality even after mutation. Electrostatic surface potential
again unveiled MT_A to be the most stable one. MT_A was thereby revealed to be
the potent peptide inhibitor for HIV. This probe presents a pathway to
investigate and compare the bio-molecular interaction of WT IL27 and MT_A IL27
(strongest model) with HIV in the future. This is the first report regarding the
structural biology of IL27 accompanied by alteration at its genetic level and
delving into the unknown residue-level and functional biochemistry for bringing
about an annihilation towards AIDS.
PMID- 26432007
TI - Ultrasound as a tool for fluid status assessment in the trauma and critically ill
patient.
AB - Resuscitation to euvolemia in trauma as well as in the critically ill patient,
continues to be a challenge. Focused cardiac ultrasound has been shown to be a
reliable tool to evaluate fluid status and to guide therapy. The present
manuscript reviews the evidence supporting the use of this tool and describes the
clinical applications for image-based resuscitation using echocardiogram.
PMID- 26432008
TI - An open-label, prospective, exploratory study of patients with epilepsy switching
from levetiracetam to brivaracetam.
AB - We evaluated nonpsychotic behavioral adverse events (BAEs) in patients receiving
levetiracetam (LEV) who switched to brivaracetam (BRV). Patients >=16 years of
age, receiving 2-3 antiepileptic drugs (AEDs), including LEV 1-3g/day, and
experiencing BAEs within 16 weeks of LEV treatment initiation, enrolled in an
open-label Phase 3b study (NCT01653262) comprising a <=1-week screening period,
an immediate switch from LEV to BRV 200mg/day (without titration), and a 12-week
treatment period. The percentages of patients with investigator-assessed
clinically meaningful reduction in BAEs, shift in maximum BAE intensity, and
change in health-related quality of life (HRQoL) (Patient-Weighted Quality of
Life in Epilepsy Inventory-Form 31 [QOLIE-31-P]) were assessed. Of 29 patients
enrolled, 26 (89.7%) completed the study. At the end of the treatment period,
27/29 (93.1%) patients switched to BRV had clinically meaningful reductions in
BAEs. Physicians reported a reduction in the maximum intensity of primary BAEs in
27/29 (93.1%) patients. Mean change from baseline to Week 12 in QOLIE-31-P total
score was 12.1, indicating improved HRQoL. During the treatment period, 23/29
(79.3%) patients reported treatment-emergent adverse events (TEAEs). One patient
reported a serious TEAE (suicidal ideation and suicide attempt). Two patients
discontinued BRV because of TEAEs. Findings from this small study suggest that
patients experiencing BAEs associated with LEV may benefit from switching to BRV.
PMID- 26432009
TI - Childhood trauma and psychogenic nonepileptic seizures: A review of findings with
speculations on the underlying mechanisms.
AB - OBJECTIVE: The objective of this review was to examine the possible link between
psychological trauma in a patient's medical history and the onset of psychogenic
nonepileptic seizures (PNES). METHODOLOGY: An electronic search of published
reports was made using the search engines PubMed-MedLine, EBSCO, PsycINFO, SFX,
and Embase and the keywords "PNES", "psychogenic seizures", "sexual abuse", and
"trauma". RESULTS: A correlation emerged between history of childhood trauma and
the presence of PNES. Antecedent trauma was more frequent in females than in
males and in patients exhibiting psychiatric disorders but was inversely
correlated with cognitive impairment. CONCLUSIONS: In the presence of PNES, it is
important to accurately investigate the patient's medical history in search of
psychological trauma, particularly in women and in patients with psychiatric
disorders.
PMID- 26432010
TI - Safety assessment of Guibi-tang: Subchronic toxicity study in Crl:CD SD rats.
AB - Guibi-tang (Kihi-To in Japanese and Qui-Pi-Tang in Chinese) is a multiherbal
traditional Korean medicinal formula used for treatment of amnesia, fatigue, poor
memory or forgetfulness, anemia, insomnia, and necrosis. The aim of the present
study was to investigate potential safety, if any, of subchronic administration
of Guibi-tang aqueous extract (GBT) in laboratory animals. For this study, 0,
1000, 2000, and 5000 mg/kg/day of GBT was administered to Crl:CD Sprague Dawley
rats (10/sex/group) for 13 weeks via oral gavage. Administration of the GBT did
not result in any mortality, body weight, food consumption, hematology, serum
biochemistry, clinical or ophthalmological signs or changes in urinalysis, gross
findings, or organ weight. However, histopathology revealed forestomach
hyperplasia and duodenum mucosal hyperplasia in rats of both sexes at the highest
dose of GBT, 5000 mg/kg/day. Therefore, the no-observed-adverse-effect level in
rats was established for GBT at 2000 mg/kg/day under the conditions of this
study.
PMID- 26432012
TI - Missouri K-12 school disaster and biological event preparedness and seasonal
influenza vaccination among school nurses.
AB - BACKGROUND: School preparedness for bioevents, such as emerging infectious
diseases, bioterrorism, and pandemics, is imperative, but historically has been
low. METHODS: The Missouri Association of School Nurses members were sent an
online survey during the 2013-2014 school year to assess current bioevent
readiness. There were 15 and 35 indicators of school disaster and bioevent
preparedness, respectively. Multivariate linear regressions were conducted to
delineate factors associated with higher school disaster and bioevent
preparedness scores. RESULTS: In total, 133 school nurses participated, with a
33.6% response rate. On average, schools had fewer than half of the disaster or
bioevent indicators. Disaster and bioevent preparedness scores ranged from 1-12.5
(mean, 6.0) and 5-25 (mean, 13.8), respectively. The least frequently reported
plan components included bioterrorism-specific psychological needs addressed
(1.5%, n = 2), having a foodservice biosecurity plan (8.3%, n = 11), and having a
liberal sick leave policy for bioevents (22.6%, n = 30). Determinants of better
bioevent preparedness include perception that the school is well prepared for a
pandemic (P = .001) or natural disaster (P < .05), nurse being on the disaster
planning committee (P = .001), and school being a closed point of dispensing (P <
.05). CONCLUSION: Schools are underprepared for biological events and are not on
track to meet state and national biological preparedness goals.
PMID- 26432013
TI - Vector representation and its application of DNA sequences based on nucleotide
triplet codons.
AB - Compared with single nucleotide, nucleotide triplet appears to contain more
biological and genetic information, so it has been applied widely. We propose a
new 3D-vector representation method of DNA sequences, namely use molecular weight
of nucleotide triplet to define the '0' molecular plane, then make the 3-D
coordinate transformation to map a DNA sequence into a curve by the coordinate
accumulation, and then extract the D/D matrix's eigenvalues to describe, compare
and analyze the DNA sequences as the numerical characterization. It is a new idea
for comparison and phylogenetic trees' reconstruction of biological sequences.
PMID- 26432014
TI - Comparative investigation of thermal and mechanical properties of cross-linked
epoxy polymers with different curing agents by molecular dynamics simulation.
AB - Molecular dynamics (MD) simulations were carried out to predict the thermal and
mechanical properties of the cross-linked epoxy system composed of DGEBA resin
and the curing agent TETA. To investigate the effects of curing agents, a
comprehensive and comparative study was also performed on the thermal and
mechanical properties of DGEBA/TETA and DGEBA/DETDA epoxy systems such as
density, glass transition temperature (Tg), coefficient of thermal expansion
(CTE) and elastic properties of different cross-linking densities and different
temperatures. The results indicated that the glass transition temperature of
DGEBA/TETA system calculated through density-temperature data, ~ 385-395 degrees
K, for the epoxy system with the cross-linking density of 62.5% has a better
agreement with the experimental value (Tg, ~ 400 degrees K) in comparison to the
value calculated through the variation of cell volume in terms of temperature,
430-440 degrees K. They also indicated that CTE related parameters and elastic
properties including Young, Bulk, and shear's moduli, and Poisson's ratio have a
relative agreement with the experimental results. Comparison between the thermal
and mechanical properties of epoxy systems of DGEBA/TETA and DGEBA/DETDA showed
that the DGEBA/DETDA has a higher Tg in all cross linking densities than that of
DGEBA/TETA, while higher mechanical properties was observed in the case of
DGEBA/TETA in almost all cross linking densities.
PMID- 26432016
TI - Modulation of Glucokinase Regulatory Protein: A Double-Edged Sword?
AB - The continuous search for drugs targeting type 2 diabetes mellitus (T2DM) has led
to the identification of small molecules that disrupt the binding between
glucokinase and glucokinase regulatory protein (GKRP). Although mice studies are
encouraging, it will take years before these disruptors can be introduced to T2DM
patients. Recently, genome-wide association studies (GWASs) have shown that
variants in the gene encoding GKRP protect against T2DM and kidney disease but
predispose to gout, nonalcoholic fatty liver disease, and dyslipidemia. These
genetic data, together with previous experience with systemic and hepatospecific
glucokinase activators, provide insight into the anticipated efficacy and safety
of small-molecule disruptors in humans. Interestingly, they suggest that the
opposite--enhanced GKRP-glucokinase binding--could be beneficial in selected
patients.
PMID- 26432017
TI - Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular
Vesicles.
AB - Extracellular vesicles (EVs) are nanosized particles (100-1000 nm) enclosed by a
phospholipid bilayer that have been described as important mediators of
intercellular communication. The role of EVs in oncobiology has been extensively
studied, including their contribution to the horizontal transfer of drug
resistance from drug-resistant to drug-sensitive cancer cells. This review
focuses on the EVs cargo responsible for this intercellular transfer of drug
resistance; namely, drug-efflux pumps, miRNAs, long noncoding RNAs (lncRNAs), and
other mediators. Additionally, the known molecular mechanisms and features of
this transfer are discussed. This is an emerging area of research and we
highlight topics that need to be further studied to fully understand and
counteract the intercellular transfer of drug resistance mediated by EVs.
PMID- 26432018
TI - Modeling Disease In Vivo With CRISPR/Cas9.
AB - The recent advent of CRISPR/Cas9-mediated genome editing has created a wave of
excitement across the scientific research community, carrying the promise of
simple and effective genomic manipulation of nearly any cell type. CRISPR has
quickly become the preferred tool for genetic manipulation, and shows incredible
promise as a platform for studying gene function in vivo. I discuss the current
application of CRISPR technology to create new in vivo disease models, with a
particular focus on how these tools, derived from an adaptive bacterial immune
system, are helping us to better model the complexity of human cancer.
PMID- 26432020
TI - Exhaled Molecular Fingerprinting in Diagnosis and Monitoring: Validating Volatile
Promises.
AB - Medical diagnosis and phenotyping increasingly incorporate information from
complex biological samples. This has promoted the development and clinical
application of non-invasive metabolomics in exhaled air (breathomics). In
respiratory medicine, expired volatile organic compounds (VOCs) are associated
with inflammatory, oxidative, microbial, and neoplastic processes. After recent
proof of concept studies demonstrating moderate to good diagnostic accuracies,
the latest efforts in breathomics are focused on optimization of sensor
technologies and analytical algorithms, as well as on independent validation of
clinical classification and prediction. Current research strategies are revealing
the underlying pathophysiological pathways as well as clinically-acceptable
levels of diagnostic accuracy. Implementing recent guidelines on validating
molecular signatures in medicine will enhance the clinical potential of
breathomics and the development of point-of-care technologies.
PMID- 26432019
TI - UBA1: At the Crossroads of Ubiquitin Homeostasis and Neurodegeneration.
AB - Neurodegenerative diseases are a leading cause of disability and early death. A
common feature of these conditions is disruption of protein homeostasis.
Ubiquitin-like modifier activating enzyme 1 (UBA1), the E1 ubiquitin-activating
enzyme, sits at the apex of the ubiquitin cascade and represents an important
regulator of cellular protein homeostasis. Critical contributions of UBA1
dependent pathways to the regulation of homeostasis and degeneration in the
nervous system are emerging, including specific disruption of UBA1 in spinal
muscular atrophy (SMA) and Huntington's disease (HD). In this review we discuss
recent findings that put UBA1 at the centre of cellular homeostasis and
neurodegeneration, highlighting the potential for UBA1 to act as a promising
therapeutic target for a range of neurodegenerative diseases.
PMID- 26432021
TI - Emerging Liver-Kidney Interactions in Nonalcoholic Fatty Liver Disease.
AB - Mounting evidence connects non-alcoholic fatty liver disease (NAFLD) to chronic
kidney disease (CKD). We review emerging mechanistic links between NAFLD and CKD,
including altered activation of angiotensin converting enzyme (ACE)-2,
nutrient/energy sensors sirtuin-1 and AMP-activated kinase, as well as impaired
antioxidant defense mediated by nuclear factor erythroid 2-related factor-2
(Nrf2). Dietary fructose excess may also contribute to NAFLD and CKD. NAFLD
affects renal injury through lipoprotein dysmetabolism and altered secretion of
the hepatokines fibroblast growth factor-21, fetuin-A, insulin-like growth factor
1, and syndecan-1. CKD may mutually aggravate NAFLD and associated metabolic
disturbances through altered intestinal barrier function and microbiota
composition, the accumulation of uremic toxic metabolites, and alterations in pre
receptor glucocorticoid metabolism. We conclude by discussing the implications of
these findings for the treatment of NAFLD and CKD.
PMID- 26432022
TI - G3BP1 restricts HIV-1 replication in macrophages and T-cells by sequestering
viral RNA.
AB - HIV-1 exploits the cellular machinery for replication and therefore several
interactions with cellular factors take place, some of which are yet unknown. We
identified GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) as a
cellular factor that restricts HIV-1, by analyzing transcriptome profiles of in
vitro-cytokine-activated macrophages that are non-permissive to HIV-1
replication. Silencing of G3BP1 by RNA interference resulted in increased HIV-1
replication in primary T-cells and macrophages, but did not affect replication of
other retroviruses. G3BP1 specifically interacted with HIV-1 RNA in the
cytoplasm, suggesting that it sequesters viral transcripts, thus preventing
translation or packaging. G3BP1 was highly expressed in resting naive or memory T
cells from healthy donors and HIV-1 infected patients, but significantly lower in
IL-2-activated T-cells. These results strongly suggest that G3BP1 captures HIV-1
RNA transcripts and thereby restricts mRNA translation, viral protein production
and virus particle formation.
PMID- 26432023
TI - Isolation and characterization of a virus infecting the freshwater algae
Chrysochromulina parva.
AB - Water samples from Lake Ontario, Canada were tested for lytic activity against
the freshwater haptophyte algae Chrysochromulina parva. A filterable lytic agent
was isolated and identified as a virus via transmission electron microscopy and
molecular methods. The virus, CpV-BQ1, is icosahedral, ca. 145nm in diameter,
assembled within the cytoplasm, and has a genome size of ca. 485kb. Sequences
obtained through PCR-amplification of DNA polymerase (polB) genes clustered among
sequences from the family Phycodnaviridae, whereas major capsid protein (MCP)
sequences clustered among sequences from either the Phycodnaviridae or
Mimiviridae. Based on quantitative molecular assays, C. parva's abundance in Lake
Ontario was relatively stable, yet CpV-BQ1's abundance was variable suggesting
complex virus-host dynamics. This study demonstrates that CpV-BQ1 is a member of
the proposed order Megavirales with characteristics of both phycodnaviruses and
mimiviruses indicating that, in addition to its complex ecological dynamics, it
also has a complex evolutionary history.
PMID- 26432024
TI - Cryo-electron microscopy and single molecule fluorescent microscopy detect CD4
receptor induced HIV size expansion prior to cell entry.
AB - Viruses are often thought to have static structure, and they only remodel after
the viruses have entered target cells. Here, we detected a size expansion of
virus particles prior to viral entry using cryo-electron microscopy (cryo-EM) and
single molecule fluorescence imaging. HIV expanded both under cell-free
conditions with soluble receptor CD4 (sCD4) targeting the CD4 binding site on the
HIV-1 envelope protein (Env) and when HIV binds to receptor on cellular membrane.
We have shown that the HIV Env is needed to facilitate receptor induced virus
size expansions, showing that the 'lynchpin' for size expansion is highly
specific. We demonstrate that the size expansion required maturation of HIV and
an internal capsid core with wild type stability, suggesting that different HIV
compartments are linked and are involved in remodelling. Our work reveals a
previously unknown event in HIV entry, and we propose that this pre-entry priming
process enables HIV particles to facilitate the subsequent steps in infection.
PMID- 26432025
TI - Visual evoked potential latencies of three-year-old children prenatally exposed
to buprenorphine or methadone compared with non-opioid exposed children: The
results of a longitudinal study.
AB - This study compared the latency of pattern reversal visual evoked potentials
(VEP) of 36-month old children exposed to opioid pharmacotherapy in utero to that
of a group of non-exposed children. Pregnant women were enrolled as part of an
open-label non-randomised flexible dosing longitudinal study. Participants were
21 children whose mothers were treated with buprenorphine- (n=11) or methadone
pharmacotherapy (n=10) during pregnancy, and 15 children not exposed to opioids
in pregnancy. One-way between groups analyses of variance (ANOVA) were conducted
to test the statistical significance of differences between the mean latencies of
the peak response to two different sized checkerboard patterns (48' and 69' of
retinal arc). Standard multiple regression analyses were conducted to determine
whether there was a significant relationship between group status and VEP
latencies after adjusting for the effect of covariates. VEP latencies ranged from
98 to 112 milliseconds (ms) for checks of 48' arc, and from 95 to 113ms for
checks of 69' arc. Latencies were comparable across groups. After adjusting for
covariates children prenatally exposed to methadone or buprenorphine did not
differ significantly from non-opioid exposed children in their responses to
either check size. Nor were there any significant differences in VEP latencies
between children prenatally exposed to methadone and children prenatally exposed
to buprenorphine. Head circumference (HC) was significantly associated with P100
latencies for both check sizes. Data from this controlled, non-randomised study
suggest that neither buprenorphine nor methadone appear to have any long-term
effects on visual maturity assessed at 36months of age.
PMID- 26432026
TI - Combined exposure to nano-silica and lead induced potentiation of oxidative
stress and DNA damage in human lung epithelial cells.
AB - Growing evidence has confirmed that exposure to ambient particulate matters (PM)
is associated with increased morbidity and mortality of cardiovascular and
pulmonary diseases. Ambient PM is a complex mixture of particles and air
pollutants. Harmful effects of PM are specifically associated with ultrafine
particles (UFPs) that can adsorb high concentrations of toxic air pollutants and
are easily inhaled into the lungs. However, combined effects of UFPs and air
pollutants on human health remain unclear. In the present study, we elucidated
the combined toxicity of silica nanoparticles (nano-SiO2), a typical UFP, and
lead acetate (Pb), a typical air pollutant. Lung adenocarcinoma A549 cells were
exposed to nano-SiO2 and Pb alone or their combination, and their combined
toxicity was investigated by focusing on cellular oxidative stress and DNA
damage. Factorial analyses were performed to determine the potential interactions
between nano-SiO2 and Pb. Our results showed that exposure of A549 cells to a
modest cytotoxic concentration of Pb alone induced oxidative stress, as evidenced
by elevated reactive oxygen species generation and lipid peroxidation, and
reduced glutathione content and superoxide dismutase and glutathione peroxidase
activities. In addition, exposure of A549 cells to Pb alone induced DNA damage,
as evaluated by alkaline comet assay. Exposure of A549 cells to non-cytotoxic
concentration of nano-SiO2 did not induce cellular oxidative stress and DNA
damage. However, exposure to the combination of nano-SiO2 and Pb potentiated
oxidative stress and DNA damage in A549 cells. Factorial analyses indicated that
the potentiation of combined toxicity of nano-SiO2 and Pb was induced by additive
or synergistic interactions.
PMID- 26432027
TI - Abatement of toxicity of effluents containing Cr(VI) by heterogeneous
photocatalysis. Toxicity assessment by AMPHITOX assay.
AB - Toxicity of a Cr(VI) solution before and after treatment by TiO2 heterogeneous
photocatalysis (HP) was performed with AMPHITOX bioassay. Changes in toxicity on
Rhinella arenarum larvae for 10-d were monitored after exposure to an untreated
Cr(VI) solution and to the same solution after HP treatment. The HP treatment of
a 41.60 mg L(-1) Cr(VI) solution reduced to 37.5% the concentration of the metal
ion. A 10-fold reduction in toxicity at acute exposure (72 h) and 150-fold
reduction in toxicity after 240 h was found. Further, the LOEC value increased
from 0.001% for the untreated solution to 0.153% after HP treatment. Moreover,
the safe concentration in untreated solution corresponded to 0.0001% sample, and
it was 0.01% after the treatment, i.e., 100 times higher. A saving of water of
about 100,000 L per L of effluent would be possible through dilution to allow
safer concentrations for discharge; the saving would reach the highest value
(1,000,000 L per L) at 240 h. Sub-lethal effects were completely absent in larvae
exposed to the treated solution. The AMPHITOX test allowed to detect chronic
effects at low Cr concentrations, i.e. at environmentally relevant levels.
PMID- 26432028
TI - Host-parasite relationships as determinants of heavy metal concentrations in
perch (Perca fluviatilis) and its intestinal parasite infection.
AB - The concentrations of As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, and Zn and their
bioconcentration factors (BCFs) were determined in two intestinal parasites, an
acanthocephalan, Acanthocephalus lucii, a tapeworm, Proteocephalus percae,
present in the same host, the European perch (Perca fluviatilis, L.), in the
heavily polluted Ruzin reservoir in eastern Slovakia. The bioaccumulation of
heavy metals in the fish organs and parasites was studied for acanthocephalan and
tapeworm monoinfections or mixed infections by the two parasites and for the size
of their parasitic infrapopulations. Bioconcentration factors
(c[parasite]/c[muscle tissue]) showed that the concentrations of As, Ni, Pb and
Zn were higher in mixed infections than in monoinfections. Negative correlations
between heavy metal concentrations in perch organs and the parasites were found.
For example, higher concentrations of Ni and Zn in both parasite species
corresponded with lower metal concentrations in perch and hard roe. Likewise,
significant negative relationships between metal concentrations in fish organs
and number of parasites were noticed with lower levels of Pb in fish harbouring
higher numbers of tapeworms. Similarly, in both parasite species the
concentrations of some essential elements (Cr, Mn) were lower at high infection
intensities compared to low intensities. Our study revealed that the differential
concentration of heavy metals in perch organs was affected by the type of
infection (mono- or mixed-infection), and needs to be considered in field
ecotoxicological and parasitological studies as a potentially important factor
influencing the pollutant concentrations in fish.
PMID- 26432029
TI - Accumulation properties of inorganic mercury and organic mercury in the red
crowned crane Grus japonensis in east Hokkaido, Japan.
AB - The red-crowned (Japanese) crane Grus japonensis is native to east Hokkaido,
Japan, in contrast to the East Asia mainland. Previously, we reported that red
crowned cranes in Hokkaido were highly contaminated with mercury in the 1990s and
that the contamination rapidly decreased to a moderate level in the 2000s. In the
present study, we determined levels of organic mercury (O-Hg) in the liver and
kidney of cranes in east Hokkaido in comparison with levels of total mercury (T
Hg). T-Hg levels in the kidneys were higher than those in the livers in adults
but not in subadults and juveniles; however, the reverse was the case for O-Hg
even for adults. The ratio of O-Hg to T-Hg in both the liver and kidney decreased
as T-Hg increased in the three developmental stages. While the ratios of O-Hg to
T-Hg in the liver and kidney of adults were significantly lower than those of
juveniles, the ratios were similar for adults and juveniles in a lower range of T
Hg. The ratio of selenium (Se) to T-Hg decreased as T-Hg increased in both the
liver and kidney, irrespective of stages. Mercury burdens in feathers were about
59% and 67% of the total body burdens for juveniles and adults, respectively.
Furthermore, ratios of carbon and nitrogen stable isotopes to T-Hg varied
greatly, with no relation to mercury level in the liver. The results suggest slow
accumulation of inorganic mercury in the kidney of red-crowned cranes in east
Hokkaido, Japan.
PMID- 26432030
TI - Generation of a de novo transcriptome from equine lamellar tissue.
AB - BACKGROUND: Laminitis, the structural failure of interdigitated tissue that
suspends the distal skeleton within the hoof capsule, is a devastating disease
that is the second leading cause of both lameness and euthanasia in the horse.
Current transcriptomic research focuses on the expression of known genes.
However, as this tissue is quite unique and equine gene annotation is largely
derived from computational predictions, there are likely yet uncharacterized
transcripts that may be involved in the etiology of laminitis. In order to create
a novel annotation resource, we performed whole transcriptome sequencing of
sagittal lamellar sections from one control and two laminitis affected horses.
RESULTS: Whole transcriptome sequencing of the three samples resulted in 113
million reads. Overall, 88 % of the reads mapped to the equCab2 reference genome,
allowing for the identification of 119,430 SNPs. The de novo assembly generated
around 75,000 transcripts, of which 36,000 corresponded to known annotations.
Annotated transcript models are hosted in a public data repository and thus can
be easily accessed or loaded into genome browsers. RT-PCR of 12 selected
assemblies confirmed structure and expression in lamellar tissue. CONCLUSIONS:
Transcriptome sequencing represents a powerful tool to expand on equine
annotation and identify novel targets for further laminitis research.
PMID- 26432031
TI - Is interpersonal counselling (IPC) sufficient treatment for depression in primary
care patients? A pilot study comparing IPC and interpersonal psychotherapy (IPT).
AB - BACKGROUND: Psychotherapeutic treatment is underused in primary care, where even
short-term psychotherapy can be perceived as too lengthy and labour-intensive. We
tested here for the first time the preliminary efficacy of seven sessions of
interpersonal counselling (IPC) by comparison with sixteen sessions of
interpersonal psychotherapy (IPT) in regular clinical settings. METHODS: Patients
seeking treatment for the first time who met the DSM-IV criteria for major
depressive disorder (MDD, mild/moderate) were randomized to either IPC (n=20) or
IPT (n=20). The efficacy of the treatments was assessed using the 34-item
Clinical Outcomes in Routine Evaluation (CORE-OM) scale and the Beck Depression
Inventory (BDI) scale. RESULTS: 90% of the patients completed all the treatment
sessions. IPC delivered by psychiatric nurses in primary care proved equally as
effective as IPT delivered by psychotherapists/psychologists in secondary care.
The pre-treatment to 12-month follow-up within-group effect sizes were large:
1.52 (CORE-OM) and 1.41 (BDI) in the IPC group and 1.58 (CORE-OM) and 1.40 (BDI)
in the IPT group. At the 12-month follow-up 59% of the patients in the IPC group
and 63% in the IPT group were classified as recovered on the CORE-OM scale, with
corresponding remission rates of 61% for both groups on the BDI scale.
LIMITATIONS: The small sample size limited the power to detect differences
between the groups and the naturalistic settings may have confounded the results.
CONCLUSIONS: This clinical trial suggests that IPC is an appropriate and even
sufficient first-phase intervention for handling previously untreated mild to
moderate depression in primary health care.
PMID- 26432032
TI - Interaction between BDNF rs6265 Met allele and low family cohesion is associated
with smaller left hippocampal volume in pediatric bipolar disorder.
AB - BACKGROUND: Genetic and environmental factors are implicated in the onset and
evolution of pediatric bipolar disorder, and may be associated to structural
brain abnormalities. The aim of our study was to assess the impact of the
interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265
polymorphism and family functioning on hippocampal volumes of children and
adolescents with bipolar disorder, and typically-developing controls. METHODS: We
evaluated the family functioning cohesion subscale using the Family Environment
Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural
brain imaging in 29 children and adolescents with bipolar disorder, and 22
healthy controls. RESULTS: We did not find significant differences between
patients with BD or controls in left or right hippocampus volume (p=0.44, and
p=0.71, respectively). However, we detected a significant interaction between low
scores on the cohesion subscale and the presence of the Met allele at BNDF on
left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None
of the factors independently (BDNF Val66Met, cohesion scores) was significantly
associated with hippocampal volume differences. LIMITATIONS: small sample size,
cross-sectional study. CONCLUSIONS: These results may lead to a better
understanding of the impact of the interaction between genes and environment
factors on brain structures associated to bipolar disorder and its
manifestations.
PMID- 26432033
TI - Association of asthma and anxiety: A nationwide population-based study in Taiwan.
AB - BACKGROUND: Few studies have investigated the bidirectional relationship between
asthma and anxiety; we sought to investigate asthma and anxiety in a large
national sample. METHODS: Cases were identified from Taiwan's National Health
Insurance Research Database with a new primary diagnosis of asthma (ICD-9:493)
aged more than 15 years between 2000 and 2007. Case status required the presence
of any inpatient diagnosis of asthma and/or at least one year diagnosis of asthma
in outpatient service. These 22,797 cases were compared to 22,797 sex-, age-,
residence- and insurance premium-matched controls and both groups were followed
until the end of 2008 for instances of anxiety, defined as ICD-9 codes 300.0,
300.01, 300.02, 300.2, 300.21, 300.23, 300.3. Competing risk adjusted Cox
regression analyses were applied, adjusting for sex, age, residence, insurance
premium, prednisone use, Charlson comorbidity index, cardiovascular disease,
diabetes, depression disorder, and hospital admission days for any disorder. The
effect of asthma on the risk of panic disorder and the effect of anxiety disorder
on the risk of later asthma were also examined as competing risk adjusted Cox
regression analyses RESULTS: Of the 45,594 subjects, 2792 were ascertained as
having anxiety during a mean (SD) follow-up period of 5.3 (2.5) years. Asthma,
females, older age, rural residence, depression disorder, and prednisone use were
independent risks on anxiety in the fully adjusted model. Anxiety, older age,
rural residence, and prednisone use were independent risks on asthma in the fully
adjusted model. LIMITATIONS: The severity of asthma and anxiety disorder, the
duration of prednisone treatment and adherence, stressful life events, smoking,
family history and relationship were not evaluated. CONCLUSIONS: Bidirectional
relationship between asthma and anxiety disorder was confirmed in this
population, in dependent of a number of potential confounding factors.
PMID- 26432034
TI - Prior suicide attempts are less common in suicide decedents who died by firearms
relative to those who died by other means.
AB - BACKGROUND: Suicide prevention efforts often center on the identification of risk
factors (e.g., prior suicide attempts); however, lists of risk factors without
consideration of context may prove incapable of impacting suicide rates. One
contextual variable worth considering is attempt method. METHODS: Utilizing data
from the National Violent Death Reporting System (2005-2012), I examined suicide
deaths (n=71,775) by firearms and other means to determine whether prior suicide
attempts were more common in one group versus the other. RESULTS: Significantly
fewer suicide decedents who died by firearms reported a prior history of suicide
attempts (12.10%) than did decedents who died by other means (28.66%). This
result was further replicated within each state that contributed data to the
NVDRS. LIMITATIONS: Only 17 states have contributed to the NVDRS thus far and,
within those states, not all suicide deaths were reported. Due to the nature of
the data, I was unable to test proposed mediators within our model. CONCLUSIONS:
Suicide decedents who die by firearms may die on their first attempt more often
than other decedents due to a capability and willingness to utilize a highly
lethal means. Current risk assessment protocols may be ill equipped to identify
such individuals prospectively on their own. Broader methods of implementing
means restriction (e.g., legislation) may thus be pivotal in suicide prevention
efforts.
PMID- 26432035
TI - Effects of alkyl side chains and terminal hydrophilicity on vitamin D receptor
(VDR) agonistic activity based on the diphenylpentane skeleton.
AB - Vitamin D receptor (VDR) is a family of nuclear receptors (NR) that regulates
physiological effects such as the immune system, calcium homeostasis, and cell
proliferation. We synthesized non-secosteroidal VDR ligands bearing a long alkyl
chain based on the diphenylpentane skeleton. The VDR-mediated transcriptional
activities of the synthesized compounds were evaluated using a reporter gene
assay and HL-60 cell differentiation-inducing assay. We herein described the
structure-activity relationship and effects of alkyl-chain length on VDR-mediated
transcriptional activity.
PMID- 26432036
TI - Synthesis, biological evaluation and structure-activity relationship studies of
isoflavene based Mannich bases with potent anti-cancer activity.
AB - Phenoxodiol, an analogue of the isoflavone natural product daidzein, is a potent
anti-cancer agent that has been investigated for the treatment of hormone
dependent cancers. This molecular scaffold was reacted with different primary
amines and secondary amines under different Mannich conditions to yield either
benzoxazine or aminomethyl substituted analogues. These processes enabled the
generation of a diverse range of analogues that were required for structure
activity relationship (SAR) studies. The resulting Mannich bases exhibited
prominent anti-proliferative effects against SHEP neuroblastoma and MDA-MB-231
breast adenocarcinoma cell lines. Further cytotoxicity studies against MRC-5
normal lung fibroblast cells showed that the isoflavene analogues were selective
towards cancer cells.
PMID- 26432037
TI - Monoamine oxidase inhibitory activities of heterocyclic chalcones.
AB - Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1
ones) possess monoamine oxidase (MAO) inhibition activities. Of particular
importance to the present study is a report that a series of furanochalcones acts
as MAO-B selective inhibitors. Since the effect of heterocyclic substitution,
other than furan (and more recently thiophene, piperidine and quinoline) on the
MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of
this study was to synthesise and evaluate further heterocyclic chalcone analogues
as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone
analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6
methoxypyridine substitution were examined. Seven of the nine synthesised
compounds exhibited IC50 values <1 MUM for the inhibition of MAO-B, with all
compounds exhibiting higher affinities for MAO-B compared to the MAO-A isoform.
The most potent MAO-B inhibitor (4h) displays an IC50 value of 0.067 MUM while
the most potent MAO-A inhibitor (4e) exhibits an IC50 value of 3.81 MUM. It was
further established that selected heterocyclic chalcones are reversible and
competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a
property linked to its thiophene moiety. We conclude that high potency chalcones
such as 4h represent suitable leads for the development of MAO-B inhibitors for
the treatment of Parkinson's disease and possibly other neurodegenerative
disorders.
PMID- 26432038
TI - A preoperative personalized risk assessment calculator for elderly ovarian cancer
patients undergoing primary cytoreductive surgery.
AB - OBJECTIVE: Cytoreductive surgery for ovarian cancer has higher rates of
postoperative complication than neoadjuvant chemotherapy followed by surgery. If
patients at high risk of postoperative complication were identified
preoperatively, primary therapy could be tailored. Our objective was to develop a
predictive model to estimate the risk of major postoperative complication after
primary cytoreductive surgery among elderly ovarian cancer patients. METHODS:
Patients who underwent primary surgery for ovarian cancer between 2005 and 2013
were identified from the National Surgical Quality Improvement Project. Patients
were selected using primary procedure CPT codes. Major complications were defined
as grade 3 or higher complications on the validated Claviden-Dindo scale. Using
logistic regression, we identified demographic and clinical characteristics
predictive of postoperative complication. RESULTS: We identified 2101 ovarian
cancer patients of whom 35.9% were older than 65. Among women older than 65, the
rate of major postoperative complication was 16.4%. Complications were directly
associated with preoperative laboratory values (serum creatinine, platelets,
white blood cell count, hematocrit), ascites, white race, and smoking status, and
indirectly associated with albumin. Our predictive model had an area under
receiver operating characteristic curve of 0.725. In order to not deny patients
necessary surgery, we chose a 50% population rate of postoperative complication
which produced model sensitivity of 9.8% and specificity of 98%. DISCUSSION: Our
predictive model uses easily and routinely obtained objective preoperative
factors to estimate the risk of postoperative complication among elderly ovarian
cancer patients. This information can be used to assess risk, manage
postoperative expectations, and make decisions regarding initial treatment.
PMID- 26432040
TI - Emerging strategies for targeting PI3K in gynecologic cancer.
AB - Ovarian, endometrial and cervical cancers are the most prevalent gynecologic
cancers in the United States and account for significant mortality. Translational
research into these cancers has highlighted the distinctive molecular and genomic
profiles of these cancers finding that, even within a disease site, the
landscapes and drivers of neoplasia are distinctive. Despite this molecular
diversity, activation of the phosphatidylinositol-3-kinase (PI3K) pathway appears
to be conserved in subsets of these tumors, suggesting that strategies that
antagonize mediators in this signaling cascade could offer anti-tumor efficacy.
Extensive pre-clinical and clinical data have demonstrated that single agent
targeted therapies lead to modest single agent activity of generally limited
duration, even in the setting of innate PI3K pathway activation via mutation or
amplification. These findings in the laboratory and clinic have prompted
investigations into resistance pathways following PI3K pathway inhibition in
order to understand escape pathways and restore tumor cell sensitivity. A next
generation of clinical trial investigations will focus on novel combinations in
order to define how these important therapeutics can be used in the clinic. This
review will present preclinical data that supports the role of the PI3K pathway
in ovarian, endometrial and cervical cancers, in addition to discussing the
reported clinical trial experience with PI3K pathway inhibition. A specific focus
will be on the rationale behind ongoing clinical trials utilizing novel agents in
concert with PI3K pathway inhibitors to reverse resistance in populations with
and without gain of function alterations in this oncogenic signaling cascade.
PMID- 26432039
TI - Groin surgery and risk of recurrence in lymph node positive patients with vulvar
squamous cell carcinoma.
AB - OBJECTIVES: Treatment of groin metastasis in vulvar squamous cell carcinoma
(VSCC) patients consists of surgery, often combined with (chemo)radiotherapy, and
is associated with significant morbidity. Our aim was to compare the risk of
groin recurrence and morbidity in patients with lymph node positive VSCC after
standard full inguinofemoral lymphadenectomy (IFL) versus less radical debulking
of clinically involved lymph nodes or removal of sentinel nodes only followed by
radiotherapy. METHODS: A retrospective cohort study of 68 patients with primary
VSCC and proven lymph node metastasis to the groin(s) was conducted. Patients
were divided into three subgroups by type of initial groin surgery (84 groins):
sentinel node (SN), IFL, and debulking of clinically involved nodes. Most
patients (82%) received adjuvant radiotherapy. Overall survival was analyzed
using time dependent cox regression. Analysis of morbidity and groin recurrence
free time was performed per groin with the generalized estimating equation model
and Kaplan Meier method. RESULTS: There was no significant difference in the risk
of developing a groin recurrence (SN 25%, debulking 16%, IFL 13%, p=0.495).
Despite the fact that more patients received radiotherapy after debulking (90% vs
67%), the complication rate was significantly lower (p=0.003) compared to IFL,
especially regarding lymphocysts and lymphedema (p=0.032 and p=0.002
respectively). CONCLUSIONS: The risk of groin recurrence was similar in all
treatment groups. Debulking of clinically involved lymph nodes was related to a
significant lower risk of complications compared to IFL. These findings support
that the preferred treatment of patients with clinically involved lymph nodes is
debulking followed by radiotherapy.
PMID- 26432041
TI - Pros and cons of vaginal brachytherapy after external beam radiation therapy in
endometrial cancer.
AB - A large number of studies have looked at the role of radiation therapy in the
treatment of endometrial cancer. One particular radiation strategy in common
practice is the use of adjuvant external beam (EB) radiotherapy followed by
vaginal brachytherapy (VB). While the addition of VB to EB provides a theoretical
benefit of a localized boost with higher focused dose to an area of potentially
high recurrence risk, a randomized clinical trial to compare outcomes and
toxicities of EB+VB vs. EB alone is lacking. The goal of this review is to
present the current data for and against the use of this combined radiation
modality and to provide some preliminary evidence regarding which patient
populations may be most likely to benefit.
PMID- 26432042
TI - Wnt signalling in gynaecological cancers: A future target for personalised
medicine?
AB - The three major gynaecological cancers, ovarian, uterine and cervical, contribute
a significant burden to global cancer mortality, and affect women in both
developed and developing countries. However, unlike other cancer types that have
seen rapid advances and incorporation of targeted treatments in recent years,
personalised medicine is not yet a reality in the treatment of gynaecological
cancers. Advances in sequencing technology and international collaborations and
initiatives such as The Cancer Genome Atlas are now revealing the molecular basis
of these cancers, and highlighting key signalling pathways involved. One pathway
which plays a role in all three cancer types, is the Wnt signalling pathway. This
complex developmental pathway is altered in most human malignancies, and members
of this pathway, particularly the recently linked ROR receptor tyrosine kinases
may be attractive future therapeutic targets. This review provides an up-to-date
summary of research into Wnt signalling and ovarian, uterine and cervical
cancers, and discusses the potential of the Wnt pathway as a future target for
personalised medicine in gynaecological cancers.
PMID- 26432043
TI - Retrospective review of symptoms and palliative care interventions in women with
advanced cervical cancer.
AB - OBJECTIVE: The objective of this study was to delineate and measure the symptom
distress experienced by patients with advanced cervical cancer at the time of
palliative care (PC) referral. METHODS: A total of 156 patients with advanced
cervical cancer were referred to PC from 2010 to 2012. Of these, 88 patients had
completed the Edmonton Symptom Assessment System (ESAS) and were included in the
analysis. RESULTS: The mean age was 45years (25-76), 47% were white, 18% were
African American, and 33% were Hispanic. Fifty-one percent were married, 64% had
no advance directives, and 75% had recurrent disease. Clinically significant
symptoms recorded by patient reported outcome measurement (defined as ESAS scores
>=4) were pain (81%), anorexia (72%), a poor feeling of well-being (70%), fatigue
(69%), and insomnia (54%). The chief complaint recorded for the visit was pain in
94% of patients. According to the PC specialists' assessment, pain (96%),
emotional distress (77%), and constipation (50%) were predominant symptoms.
Various PC interventions including opioids, laxatives, and expressive supportive
counseling were provided. Clinically significant symptoms including nausea,
depression, anxiety, and feeling of well-being were significantly improved at
follow-up visits. CONCLUSION: More than half of patients with advanced cervical
cancer were significantly burdened with pain, anorexia, a poor feeling of well
being, fatigue, insomnia, and constipation at the time of PC referral. This
research is an integral step towards developing a standardized tool for assessing
symptoms in women diagnosed with cervical cancer and thus maximizing
effectiveness of patient centered care.
PMID- 26432044
TI - PIAS3, SHP2 and SOCS3 Expression patterns in Cervical Cancers: Relevance with
activation and resveratrol-caused inactivation of STAT3 signaling.
AB - OBJECTIVE: Resveratrol inhibits cervical cancer (CC) cells by blocking STAT3
signaling. However, the mechanism of resveratrol-induced STAT3 inactivation
remains largely unknown. SHP2, PIAS3, and SOCS3 are STAT3 negative regulators;
therefore, their statuses in cervical adenocarcinoma (HeLa) and squamous cell
carcinoma (SiHa and C33A) cell lines without and with resveratrol treatment and
their correlation with STAT3 activation in CC specimens were investigated.
METHODS: MTT and TUNEL assays were used to check the resveratrol sensitivity of
CC cells, and immunocytochemical staining, Western blotting, and RT-PCR were used
to analyze SHP2, PIAS3, and SOCS3 expression and the intracellular distribution
of STAT3. Tissue microarray based immunohistochemical staining was performed to
investigate potential correlations between SHP2, PIAS3, and SOCS3 expression and
STAT3 activation. RESULTS: PIAS3 and SOCS3 were found to be weakly expressed in
CC cells and upregulated by resveratrol; this was accompanied by inhibition of
STAT3 signaling. The SHP2 level remained unchanged in all three cell lines after
resveratrol treatment. STAT3 nuclear translocation was more frequent in
adenocarcinomas and squamous cell carcinomas than that of their noncancerous
counterparts. The SOCS3 level and detection rate were higher in noncancerous
squamous cells (but not in glandular epithelia) compared with their cancerous
counterparts. The phospho-SHP2 detection rate was similar in noncancerous and
tumor tissues of squamous and glandular origins; however, PIAS3 levels were
distinct. CONCLUSIONS: Of the three STAT3 negative regulators, PIAS3 correlated
most negatively with STAT3 nuclear translocation and may inhibit STAT3 signaling
in both histological CC subtypes. PIAS3 responsiveness may reflect greater
resveratrol sensitivity and improved therapeutic outcome in CCs.
PMID- 26432045
TI - Eating with our eyes: From visual hunger to digital satiation.
AB - One of the brain's key roles is to facilitate foraging and feeding. It is
presumably no coincidence, then, that the mouth is situated close to the brain in
most animal species. However, the environments in which our brains evolved were
far less plentiful in terms of the availability of food resources (i.e.,
nutriments) than is the case for those of us living in the Western world today.
The growing obesity crisis is but one of the signs that humankind is not doing
such a great job in terms of optimizing the contemporary food landscape. While
the blame here is often put at the doors of the global food companies - offering
addictive foods, designed to hit 'the bliss point' in terms of the pleasurable
ingredients (sugar, salt, fat, etc.), and the ease of access to calorie-rich
foods - we wonder whether there aren't other implicit cues in our environments
that might be triggering hunger more often than is perhaps good for us. Here, we
take a closer look at the potential role of vision; Specifically, we question the
impact that our increasing exposure to images of desirable foods (what is often
labelled 'food porn', or 'gastroporn') via digital interfaces might be having,
and ask whether it might not inadvertently be exacerbating our desire for food
(what we call 'visual hunger'). We review the growing body of cognitive
neuroscience research demonstrating the profound effect that viewing such images
can have on neural activity, physiological and psychological responses, and
visual attention, especially in the 'hungry' brain.
PMID- 26432047
TI - Chemotherapy plus ponatinib: a new standard for Ph-positive ALL?
PMID- 26432046
TI - Combination of hyper-CVAD with ponatinib as first-line therapy for patients with
Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre,
phase 2 study.
AB - BACKGROUND: Combination of chemotherapy with a tyrosine-kinase inhibitor is
effective in the treatment of Philadelphia chromosome-positive acute
lymphoblastic leukaemia. Ponatinib is a more potent BCR-ABL1 inhibitor than all
other tyrosine-kinase inhibitors and selectively suppresses the resistant T315I
clones. We examined the activity and safety of combining chemotherapy with
ponatinib for patients with Philadelphia chromosome-positive acute lymphoblastic
leukaemia in this continuing phase 2 trial. METHODS: In this single-centre, phase
2, single-arm trial, adult patients with previously untreated Philadelphia
chromosome-positive acute lymphoblastic leukaemia were sequentially enrolled.
Patients who had received fewer than two courses of previous chemotherapy with or
without tyrosine-kinase inhibitors were also eligible. Patients had to be aged 18
years or older, have an Eastern Cooperative Oncology Group performance status of
2 or less, have normal cardiac function (defined by ejection fraction above 50%),
and have adequate organ function (serum bilirubin <=3.0 mg/dL and serum
creatinine <=3.0 mg/dL, unless higher concentrations were believed to be due to a
tumour). Patients received eight cycles of hyperfractionated cyclophosphamide,
vincristine, doxorubicin, and dexamethasone (hyper-CVAD) alternating with high
dose methotrexate and cytarabine every 21 days. Ponatinib 45 mg was given daily
for the first 14 days of cycle 1 then continuously for the subsequent cycles.
Patients in complete remission received maintenance with ponatinib 45 mg daily
with vincristine and prednisone monthly for 2 years followed by ponatinib
indefinitely. The primary endpoint for this study was event-free survival. The
trial is registered at ClinicalTrials.gov, number NCT01424982. FINDINGS: 37
patients were enrolled and treated from Nov 1, 2011, to Sept 1, 2013. 2-year
event-free survival rate was 81% (95% CI 64-90). Grade 3 or more toxic effects
included infections during induction (20 [54%] patients), increased aspartate
aminotransferase and alanine aminotransferase concentration (14 [38%] patients),
thrombotic events (three [8%]), myocardial infarction (three [8%]), hypertension
(six [16%]), skin rash (eight [22%]), and pancreatitis (six [16%] patients). Two
patients died from from myocardial infarction potentially related to treatment;
another patient also died from myocardial infarction related to sepsis. Two
further patients died, one from bleeding and another from infection, both deemed
unrelated to treatment. INTERPRETATION: The first results of this ongoing trial
indicate that the combination of chemotherapy with ponatinib is effective in
achieving early sustained remissions in patients with newly diagnosed
Philadelphia chromosome-positive acute lymphoblastic leukaemia. New strategies,
including dosing titration of ponatinib and optimised control of vascular risk
factors, might further improve outcomes. FUNDING: ARIAD Pharmaceuticals Inc.
PMID- 26432048
TI - Dietary pantothenic acid depressed the gill immune and physical barrier function
via NF-kappaB, TOR, Nrf2, p38MAPK and MLCK signaling pathways in grass carp
(Ctenopharyngodon idella).
AB - This study explored the effects of pantothenic acid (PA) on the immune and
physical barrier function, and relative mRNA levels of signaling molecules in the
gill of grass carp (Ctenopharyngodon idella). The results indicated that compared
with optimal PA supplementation, PA deficiency (1.31 mg/kg diet) decreased gill
interleukin 10, transforming growth factor beta1, inhibitor of kappaBalpha
(IkappaBalpha), eIF4E-binding protein 2, Claudin b and ZO-1 mRNA levels; anti
superoxide anion activity, and activities and mRNA levels of copper/zinc
superoxide dismutase, manganese superoxide dismutase, glutathione peroxidase,
glutathione reductase and NF-E2-related factor (P < 0.05). Additionally, PA
deficiency and excess (75.08 mg/kg diet) decreased gill complement 3 and
glutathione contents, lysozyme and acid phosphatase, anti-hydroxy radical,
catalase and glutathione S-transferases activities, and liver-expression
antimicrobial peptide 2, hepcidin, Claudin 3, Claudin c and Occludin mRNA levels
(P < 0.05). Conversely, PA deficiency increased gill reactive oxygen species and
protein carbonyl contents, and interferon gamma2, interleukin 8, nuclear factor
kappa B P65, Claudin 15a, Kelch-like ECH-associating protein 1a and Kelch-like
ECH-associating protein 1b mRNA levels (P<0.05). Moreover, PA deficiency and
excess increased gill malondialdehyde content, and tumor necrosis factor alpha,
interleukin 1beta, IkappaB kinase alpha, IkappaB kinase beta, IkappaB kinase
gamma, target of rapamycin and ribosomal S6 protein kinase1 p38 mitogen-activated
protein kinases and myosin light-chain kinase mRNA levels (P<0.05). In
conclusion, PA deficiency decreased immune and physical barrier function, and
regulated relative mRNA levels of signaling molecules in fish gill. Based on the
quadratic regression analysis of gill lysozyme activity, the optimal PA levels in
grass carp (253.44-745.25 g) were estimated to be 36.97 mg/kg diet.
PMID- 26432049
TI - Lvserpin3 is involved in shrimp innate immunity via the inhibition of bacterial
proteases and proteases involved in prophenoloxidase system.
AB - Serine protease inhibitor, represented by serpin, plays an important inhibitory
role on proteases involved in the immune responses. To clarify the immune
characterizations of serpin, a novel serpin (Lvserpin3) encoding for 410 amino
acids with a 23-amino acid signal peptide and a serpin domain was identified from
the Pacific white shrimp Litopenaeus vannamei. Lvserpin3 expressed strongest in
hepatopancreas, and was significantly up-regulated in the early stage upon Vibrio
anguillarum, Micrococcus lysodeikticus or White Spot Syndrome Virus (WSSV)
infection. Suppression of Lvserpin3 by dsRNA led to a significant increase in the
transcripts of LvPPAF, LvproPO and phenoloxidase (PO) activity, and also led to
the high cumulative mortality. The recombinant Lvserpin3 protein (rLvserpin3)
inhibited the proteases secreted by M. lysodeikticus and Bacillus subtilis, and
further exhibited inhibitory role on the growth of B. subtilis and M.
lysodeikticu. Moreover, rLvserpin3 was found to be able to block the activation
of prophenoloxidase system. Taken together, the results imply that Lvserpin3 may
be involved in shrimp innate immunity via the inhibition of bacterial proteases
and proteases involved in prophenoloxidase system.
PMID- 26432050
TI - Comment on arterial flow waveforms, vascular tone, and chronic fatigue by Zundel
et al.
PMID- 26432051
TI - Diversity of group A rotavirus on a UK pig farm.
AB - Group A rotaviruses (GARV) are a significant cause of enteritis in young pigs.
The aim of this study was to extend our understanding of the molecular
epidemiology of porcine GARV in the UK by investigating the genetic diversity of
GARV on a conventional farrow-to-finish farm. Faecal samples were obtained from
six batches of pigs in 2009 and 8 batches in 2010, when the pigs were 2, 3 (time
point omitted in 2009), 4, 5, 6 and 8 weeks of age. Presence of rotavirus was
detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in 89% and
80% of samples from 2009 and 2010, respectively. A combination of multiplex PCRs
and sequencing identified four VP7 genotypes (G2, G3, G4 and G5) and three VP4
genotypes (P[6], P[7] and P[32]) present in almost every combination over the 2
years. The predominant genotype combination was G5P[32] in 2009 and G4P[32] in
2010. Conservation among the P[32] sequences between 2009 and 2010 suggests that
reassortment may have led to the different genotype combinations. There were
significant changes in the predominant VP7 genotype prior to weaning at 4 weeks,
and post weaning when pigs were moved to a different building. Phylogenetic
analysis indicated that introduction of new viruses onto the farm was limited.
Taken together, these findings suggest that genetically diverse GARV strains
persist within the farm environment.
PMID- 26432052
TI - Screening young athletes for prevention of sudden cardiac death: Practical
recommendations for sports physicians.
AB - Regular intensive exercise in athletes increases the relative risk of sudden
cardiac death (SCD) compared with the relatively sedentary population. Most cases
of SCD are due to silent cardiovascular diseases, and pre-participation screening
of athletes at risk of SCD is thus of major importance. However, medical
guidelines and recommendations differ widely between countries. In Italy, the
National Health System recommends pre-participation screening for all competitive
athletes including personal and family history, a physical examination, and a
resting 12-lead electrocardiogram (ECG). In the United States, the American
College of Cardiology and the American Heart Association recommend a pre
participation screening program limited to the use of specific questionnaires and
a clinical examination. The value of a 12-lead ECG is debated based on issues
surrounding cost-efficiency and feasibility. The aim of this review was to focus
on (i) the incidence rate of cardiac diseases in relation to SCD; (ii) the value
of conducting a questionnaire and a physical examination; (iii) the value of a 12
lead resting ECG; (iv) the importance of other cardiac evaluations in the
prevention of SCD; and (v) the best practice for pre-participation screening.
PMID- 26432053
TI - A process for energy-efficient high-solids fed-batch enzymatic liquefaction of
cellulosic biomass.
AB - The enzymatic hydrolysis of cellulosic biomass is a key step in the biochemical
production of fuels and chemicals. Economically feasible large-scale
implementation of the process requires operation at high solids loadings, i.e.,
biomass concentrations >15% (w/w). At increasing solids loadings, however,
biomass forms a high viscosity slurry that becomes increasingly challenging to
mix and severely mass transfer limited, which limits further addition of solids.
To overcome these limitations, we developed a fed-batch process controlled by the
yield stress and its changes during liquefaction of the reaction mixture. The
process control relies on an in-line, non-invasive magnetic resonance imaging
(MRI) rheometer to monitor real-time evolution of yield stress during
liquefaction. Additionally, we demonstrate that timing of enzyme addition
relative to biomass addition influences process efficiency, and the upper limit
of solids loading is ultimately limited by end-product inhibition as soluble
glucose and cellobiose accumulate in the liquid phase.
PMID- 26432054
TI - Production of bioactive chitosan oligosaccharides using the
hypertransglycosylating chitinase-D from Serratia proteamaculans.
AB - The biological activities of chitosan and its oligosaccharides are greatly
influenced by properties such as the degree of polymerization (DP), degree of
acetylation (DA) and pattern of acetylation (PA). Here, structurally diverse
chitosan oligosaccharides from chitosan polymers (DA=35% or 61%) were generated
using Serratia proteamaculans wild-type chitinase D (SpChiD) and the W114A mutant
which lacks transglycosylase activity. The crude oligosaccharide mixtures and
purified fractions with specific DP and DA ranges were tested for their ability
to induce an oxidative burst in rice cell suspension cultures. The crude mixtures
were more active when produced by the W114A mutant whereas the purified fractions
were more active when produced by wild-type SpChiD. Neither hydrolysis nor
transglycosylation by SpChiD was inhibited in the presence of fully-deacetylated
oligosaccharides, suggesting that SpChiD could be exploited to generate
oligosaccharides with defined DA and PA values.
PMID- 26432055
TI - A novel configuration for an anaerobic submerged membrane bioreactor (AnSMBR).
Long-term treatment of municipal wastewater under psychrophilic conditions.
AB - A novel design for a pilot scale anaerobic submerged membrane bioreactor (AnSMBR)
equipped with an ultrafiltration unit, treating municipal wastewater at 18 +/- 2
degrees C, and inoculated with a mesophilic inoculum without acclimation, was
implemented and evaluated over 3 years of stable operation. The AnSMBR operated
with a volumetric loading rate between 1.6 to 2.0 kg COD/m(3)UASBd, 12.8 to 14.2h
hydraulic retention time, and reached a tCOD removal efficiency of around 90%.
Biosolid production was between 0.05 and 0.083 g VS/g CODremoved. Dissolved
methane oversaturation in the effluent was observed, reaching average values of
19.1 +/- 0.84 mg CH4/L. The permeate flow rate ranged from 10 to 14L/m(2)h with
trans-membrane pressure (TMP) values of 400-550 mbar, using cycles of 30s
backwash, 7.5 min filtration, and continuous biogas sparging (9-16 m/h). During
the three years of continuous operation, the membrane was not physically or
chemically cleaned.
PMID- 26432056
TI - Physico-chemical and biological characteristics of compost from decentralised
composting programmes.
AB - Composts that originated from small-scale composting programmes including home,
community and canteen waste composters were studied. Heavy metals concentration
indicated compliance with current regulations for conventional and organic
agriculture. Compost from canteen waste showed high organic matter content (74%
VS), while community (44 +/- 20% VS) and home composts (31 +/- 16% VS) had
moderate levels. N content increased from home compost (1.3 +/- 0.9% dm) to
community (2.0 +/- 0.9%) and canteen compost (2.5-3.0%) while P content ranged
from 0.4% to 0.6% dm. C/N, absorbance E4/E6 and N-NH4(+)/N-NO3(-) ratios as well
as respiration index indicated well-stabilized final products. Culturable
bacterial and fungal cfu linkage to composting dynamics were identified and
higher diversity of invertebrates was found in the smaller scale static systems.
With similar process evolution indicators to industrial systems, overall results
support the sustainability of these small-scale, self-managed composting systems.
PMID- 26432057
TI - Fermentation of sweet sorghum derived sugars to butyric acid at high titer and
productivity by a moderate thermophile Clostridium thermobutyricum at 50 degrees
C.
AB - In this study, a moderate thermophile Clostridium thermobutyricum is shown to
ferment the sugars in sweet sorghum juice treated with invertase and supplemented
with tryptone (10 g L(-1)) and yeast extract (10 g L(-1)) at 50 degrees C to 44 g
L(-1) butyrate at a calculated highest volumetric productivity of 1.45 g L(-1)h(
1) (molar butyrate yield of 0.85 based on sugars fermented). This volumetric
productivity is among the highest reported for batch fermentations. Sugars from
acid and enzyme-treated sweet sorghum bagasse were also fermented to butyrate by
this organism with a molar yield of 0.81 (based on the amount of cellulose and
hemicellulose). By combining the results from juice and bagasse, the calculated
yield of butyric acid is approximately 90 kg per tonne of fresh sweet sorghum
stalk. This study demonstrates that C. thermobutyricum can be an effective
microbial biocatalyst for production of bio-based butyrate from renewable
feedstocks at 50 degrees C.
PMID- 26432058
TI - Essential Thrombocythemia: The Dermatologic Point of View.
AB - Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by
an increase in blood platelets and dominated by a predisposition to vascular
events. Cutaneous manifestations can complicate its course. itching has been the
most common symptom reported; however, the percentage has ranged from 3% to 46%,
depending on the survey. Erythromelalgia is found in 6% of cases, and livedo
reticularis, minor bleeding, acrocyanosis, and Raynaud's phenomenon are rare
manifestations. It is important to recognize and treat these events, because they
can affect patients' quality of life and could worsen the prognosis. In addition
to skin involvement as a possible sign of ET, the treatment of ET can be
associated with cutaneous complications. Hydroxycarbamide, interferon-alfa, and
anagrelide can induce different skin lesions. Hydroxycarbamide has been
associated with major complications, including painful leg ulcers and actinic
keratoses. Minor events include alopecia and hyperpigmentation. Xerosis,
pruritus, and photosensitivity are some of the complications reported by patients
treated with interferon-alfa. Anagrelide has proved to be associated with fewer
dermatologic effects, only detected in single cases. Knowledge of the ET
cutaneous manifestations, together with the clinical examination findings, can
result in an earlier diagnosis and the start of effective treatment.
PMID- 26432059
TI - Facial lesions in frontal fibrosing alopecia (FFA): Clinicopathological features
in a series of 12 cases.
AB - BACKGROUND: Facial lesions in frontal fibrosing alopecia (FFA) have been poorly
described in published series. OBJECTIVE: We sought to describe facial lesions in
FFA. METHODS: We reviewed our series of 55 cases of FFA, selecting 12 cases with
clinically significant facial lesions. We performed a histologic study of these
lesions. RESULTS: In addition to the observations already described in the
literature such as facial papules or follicular red dots, we observed
perifollicular and diffuse erythema, sometimes with a reticular pattern, and the
gradual appearance of pigmented macules on facial skin. Biopsy specimens from the
areas with facial erythema showed perifollicular and interfollicular lymphocytic
infiltrate and fibrosis around vellus hair follicles. Histologic evaluation of
pigmented macules sometimes exhibited an increased epidermal pigmentation and on
occasions, pigmentary incontinence. LIMITATIONS: More patients are needed to
determine the prevalence of these lesions in FFA. CONCLUSION: On facial skin of
patients with FFA, we can observe papules or perifollicular erythema secondary to
vellus hair follicle involvement. We describe diffuse erythema, owing to
follicular and interfollicular lichenoid infiltrate, and the gradual appearance
of pigmented macules, which could be secondary to an increased epidermal
pigmentation or to pigmentary incontinence.
PMID- 26432060
TI - Quantification of bovine oxylipids during intramammary Streptococcus uberis
infection.
AB - Streptococcus uberis mastitis results in severe mammary tissue damage in dairy
cows due to uncontrolled inflammation. Oxylipids are potent lipid mediators that
orchestrate pathogen-induced inflammatory responses, however, changes in oxylipid
biosynthesis during S. uberis mastitis are unknown. Thus, the current objective
was to determine how oxylipid concentrations change in milk and mammary tissues
during different stages of S. uberis mastitis. Increased arachidonic acid and
linoleic acid-derived oxylipids were significantly increased in S. uberis
infected bovine mammary tissue. Linoleic acid metabolites, hydroxyoctadecadienoic
acid (HODE) and oxooctadecadienoic acid, predominated in tissue and milk.
Furthermore, in vitro exposure of bovine mammary endothelial cells to 13
hydroperoxyoctadecadienoic acid, upstream metabolite of HODE, significantly
increased cyclooxygenase-2 expression, but 13-HODE exposure had no effect. The
findings in the current study indicate lipidomic profiling may explain some of
the dynamics of inflammation during bacterial challenge, however continued
research is necessary to determine sample compartments which best reflect disease
pathogenesis.
PMID- 26432061
TI - Robotic stereotactic radioablation of breast tumors: Influence of beam size on
the absorbed dose distributions.
AB - Robotic stereotactic radioablation (RSR) therapy for breast tumors has been shown
to be an effective treatment strategy when applied concomitantly with
chemotherapy, with the purpose of reducing the tumor volume thus making it more
amenable for breast conserving surgery. In this paper we used Monte Carlo
simulation within a realistic patient model to determine the influence that the
variation in beam collimation radius has on the resultant absorbed dose
distributions for this type of treatment. Separate optimized plans were obtained
for treatments using 300 circular beams with radii of 0.5 cm, 0.75 cm, 1.0 cm and
1.5 cm. Cumulative dose volume histograms were obtained for the gross, clinical
and planning target volumes as well as for eight organs and structures at risk.
Target coverage improves as the collimator size is increased, at the expense of
increasing the volume of healthy tissue receiving mid-level absorbed doses.
Interestingly, it is found that the maximum dose imparted to the skin is highly
dependent on collimator size, while the dosimetry of other structures, such as
both the ipsilateral and contralateral lung tissue are basically unaffected by a
change in beam size.
PMID- 26432062
TI - Characteristics of initial deposition and behavior of radiocesium in forest
ecosystems of different locations and species affected by the Fukushima Daiichi
Nuclear Power Plant accident.
AB - After the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, information
about stand-level spatial patterns of radiocesium initially deposited in the
surrounding forests was essential for predicting the future dynamics of
radiocesium and suggesting a management plan for contaminated forests. In the
first summer (approximately 6 months after the accident), we separately estimated
the amounts of radiocesium ((134)Cs and (137)Cs; Bq m(-2)) in the major
components (trees, organic layers, and soils) in forests of three sites with
different contamination levels. For a Japanese cedar (Cryptomeria japonica)
forest studied at each of the three sites, the radiocesium concentration greatly
differed among the components, with the needle and organic layer having the
highest concentrations. For these cedar forests, the proportion of the (137)Cs
stock in the aboveground tree biomass varied from 22% to 44% of the total (137)Cs
stock; it was 44% in highly contaminated sites (7.0 * 10(5) Bq m(-2)) but reduced
to 22% in less contaminated sites (1.1 * 10(4) Bq m(-2)). In the intermediate
contaminated site (5.0-5.8 * 10(4) Bq m(-2)), 34% of radiocesium was observed in
the aboveground tree biomass of the Japanese cedar stand. However, this
proportion was considerably smaller (18-19%) in the nearby mixed forests of the
Japanese red pine (Pinus densiflora) and deciduous broad-leaved trees. Non
negligible amounts of (134)Cs and (137)Cs were detected in both the sapwood and
heartwood of all the studied tree species. This finding suggested that the uptake
or translocation of radiocesium had already started within 6 months after the
accident. The belowground compartments were mostly present in the organic layer
and the uppermost (0-5 cm deep) mineral soil layer at all the study sites. We
discussed the initial transfer process of radiocesium deposited in the forest and
inferred that the type of initial deposition (i.e., dry versus wet radiocesium
deposition), the amount of rainfall after the accident, and the leaf biomass by
the tree species may influence differences in the spatial pattern of radiocesium
by study plots. The results of the present study and further studies of the
spatial pattern of radiocesium are important for modeling future radiocesium
distribution in contaminated forest ecosystems.
PMID- 26432063
TI - A longitudinal study of accommodative changes in biometry during incipient
presbyopia.
AB - PURPOSE: To profile accommodative biometric changes longitudinally and to
determine the influence of age-related ocular structural changes on the
accommodative response prior to the onset of presbyopia. METHODS: Twenty
participants (aged 34-41 years) were reviewed at six-monthly intervals over two
and a half years. At each visit, ocular biometry was measured with the LenStar
biometer (www.Haag-Streit.com) in response to 0.00, 3.00 and 4.50 D stimuli.
Accommodative responses were measured by the WAM 5500 Auto Ref/Keratometer
(www.grandseiko.com). RESULTS: During accommodation, anterior chamber depth
reduced (F = 29, p < 0.001), whereas crystalline lens thickness (F = 39, p <
0.001) and axial length (F = 5.4, p = 0.009) increased. The accommodative
response (F = 5.5, p = 0.001) and the change in anterior chamber depth (F = 3.1,
p = 0.039), crystalline lens thickness (F = 3.0, p = 0.042) and axial length (F =
2.5, p = 0.038) in response to the 4.50 D accommodative target reduced after 2.5
years. However, the change in anterior chamber depth (F = 2.2, p = 0.097),
crystalline lens thickness (F = 1.7, p = 0.18) and axial length (F = 1.0, p =
0.40) per dioptre of accommodation exerted remained invariant after 2.5 years.
The increase in disaccommodated crystalline lens thickness with age was not
significantly associated with the reduction in accommodative response (R = 0.32,
p = 0.17). CONCLUSION: Despite significant age-related structural changes in
disaccommodated biometry, the change in biometry per dioptre of accommodation
exerted remained invariant with age. The present study supports the Helmholtz
theory of accommodation and suggests an increase in lenticular stiffness is
primarily responsible for the onset of presbyopia.
PMID- 26432064
TI - Long term mortality in a population-based cohort of adolescents, and young and
middle-aged adults with burn injury in Western Australia: A 33-year study.
AB - BACKGROUND: Advances in the treatment and management of burn patients over the
past decades have resulted in a decline of in-hospital mortality rates. Current
estimates of burn-related mortality are usually in the context of deaths
occurring during the admission or within a short time period after the incident
burn. Limited data are available that examine long term mortality after burn
injury. This study aimed to assess the impact of burn injury on long-term
mortality and quantify any increased risk of death attributable to burn injury.
METHODS: A population-based cohort study of persons 15-44 years of age
hospitalised for burn injury (n=14,559) in Western Australia (1980-2012) and a
matched non-injured comparison group (n=56,822) using linked health
administrative data was used. Hospital morbidity and death data were obtained
from the Western Australian Hospital Morbidity Data System and Death Register. De
identified extraction of all linked hospital morbidity and death records for the
period 1980-2012 were provided by the Western Australian Data Linkage System.
Survival analysis was conducted using the Kaplan-Meier method and Cox
proportional hazards modelling. RESULTS: The adjusted all-cause Mortality Rate
Ratio (MRR) for burn injury was 1.8 (95%CI: 1.7-2.0); those with burn injury had
a 1.8 times greater rate of mortality than those with no injury. The index burn
injury was estimated to account for 44% of all recorded deaths in the burn injury
cohort during the study period after discharge. Increased risk of mortality was
observed for both severe (MRR, 95%CI: 1.9, 1.3-2.9) and minor (MRR, 95%CI: 2.5,
2.2-3.0) burns. CONCLUSIONS: An increased risk of long-term all-cause mortality
is associated with both minor and severe burn injury. Estimates of total
mortality burden based on the early in-patient period alone, significantly
underestimates the true burden of burn injury in adolescents, and young and
middle aged adults. These results have significant implications for burn injury
prevention.
PMID- 26432065
TI - Finite element comparison of human and Hybrid III responses in a frontal impact.
AB - The improvement of finite element (FE) Human Body Models (HBMs) has made them
valuable tools for investigating restraint interactions compared to
anthropomorphic test devices (ATDs). The objective of this study was to evaluate
the effect of various combinations of safety restraint systems on the sensitivity
of thoracic injury criteria using matched ATD and Human Body Model (HBM)
simulations at two crash severities. A total of seven (7) variables were
investigated: 3-point belt with two (2) load limits, frontal airbag, knee bolster
airbag, a buckle pretensioner, and two (2) delta-v's - 40kph and 50kph. Twenty
four (24) simulations were conducted for the Hybrid III ATD FE model and repeated
with a validated HBM for 48 total simulations. Metrics tested in these conditions
included sternum deflection, chest acceleration, chest excursion, Viscous
Criteria (V*C) criteria, pelvis acceleration, pelvis excursion, and femur forces.
Additionally, chest band deflection and rib strain distribution were measured in
the HBM for additional restraint condition discrimination. The addition of a
frontal airbag had the largest effect on the occupant chest metrics with an
increase in chest compression and acceleration but a decrease in excursion. While
the THUMS and Hybrid III occupants demonstrated the same trend in the chest
compression measurements, there were conflicting results in the V*C,
acceleration, and displacement metrics. Similarly, the knee bolster airbag had
the largest effect on the pelvis with a decrease in acceleration and excursion.
With a knee bolster airbag the simulated occupants gave conflicting results, the
THUMS had a decrease in femur force and the ATD had an increase. Preferential use
of dummies or HBM's is not debated; however, this study highlights the ability of
HBM metrics to capture additional chest response metrics.
PMID- 26432066
TI - Failure mode and effective analysis ameliorate awareness of medical errors: a 4
year prospective observational study in critically ill children.
AB - BACKGROUND: Errors in are estimated to occur with an incidence of 3.7-16.6% in
hospitalized patients. The application of systems for detection of adverse events
is becoming a widespread reality in healthcare. Incident reporting (IR) and
failure mode and effective analysis (FMEA) are strategies widely used to detect
errors, but no studies have combined them in the setting of a pediatric intensive
care unit (PICU). AIM: The aim of our study was to describe the trend of IR in a
PICU and evaluate the effect of FMEA application on the number and severity of
the errors detected. METHODS: With this prospective observational study, we
evaluated the frequency IR documented in standard IR forms completed from January
2009 to December 2012 in the PICU of Woman's and Child's Health Department of
Padova. On the basis of their severity, errors were classified as: without
outcome (55%), with minor outcome (16%), with moderate outcome (10%), and with
major outcome (3%); 16% of reported incidents were 'near misses'. We compared the
data before and after the introduction of FMEA. RESULTS: Sixty-nine errors were
registered, 59 (86%) concerning drug therapy (83% during prescription). Compared
to 2009-2010, in 2011-2012, we noted an increase of reported errors (43 vs 26)
with a reduction of their severity (21% vs 8% 'near misses' and 65% vs 38% errors
with no outcome). CONCLUSION: With the introduction of FMEA, we obtained an
increased awareness in error reporting. Application of these systems will improve
the quality of healthcare services.
PMID- 26432067
TI - Serial [18F]-fluoromisonidazole PET during radiochemotherapy for locally advanced
head and neck cancer and its correlation with outcome.
AB - PURPOSE: The aim was to assess changes of tumour hypoxia during primary
radiochemotherapy (RCT) for head and neck cancer (HNC) and to evaluate their
relationship with treatment outcome. MATERIAL AND METHODS: Hypoxia was assessed
by FMISO-PET in weeks 0, 2 and 5 of RCT. The tumour volume (TV) was determined
using FDG-PET/MRI/CT co-registered images. The level of hypoxia was quantified on
FMISO-PET as TBRmax (SUVmaxTV/SUVmean background). The hypoxic subvolume (HSV)
was defined as TV that showed FMISO uptake ?1.4 times blood pool activity.
RESULTS: Sixteen consecutive patients (T3-4, N+, M0) were included (mean follow
up 31, median 44months). Mean TBRmax decreased significantly (p<0.05) from 1.94
to 1.57 (week 2) and 1.27 (week 5). Mean HSV in week 2 and week 5 (HSV2=5.8ml,
HSV3=0.3ml) were significantly (p<0.05) smaller than at baseline (HSV1=15.8ml).
Kaplan-Meier plots of local recurrence free survival stratified at the median
TBRmax showed superior local control for less hypoxic tumours, the difference
being significant at baseline and after 2weeks (p=0.031, p=0.016). CONCLUSIONS:
FMISO-PET documented that in most HNC reoxygenation starts early during RCT and
is correlated with better outcome.
PMID- 26432068
TI - Experimental Transmission of African Swine Fever (ASF) Low Virulent Isolate
NH/P68 by Surviving Pigs.
AB - African swine fever (ASF) has persisted in Eastern Europe since 2007, and two
endemic zones have been identified in the central and southern parts of the
Russian Federation. Moderate- to low-virulent ASF virus isolates are known to
circulate in endemic ASF-affected regions. To improve our knowledge of virus
transmission in animals recovered from ASF virus infection, an experimental in
vivo study was carried out. Four domestic pigs were inoculated with the NH/P68
ASF virus, previously characterized to develop a chronic form of ASF. Two
additional in-contact pigs were introduced at 72 days post-inoculation (dpi) in
the same box for virus exposure. The inoculated pigs developed a mild form of the
disease, and the virus was isolated from tissues in the inoculated pigs up to 99
dpi (pigs were euthanized at 36, 65, 99 and 134 dpi). In-contact pigs showed mild
or no clinical signs, but did become seropositive, and a transient viraemia was
detected at 28 days post-exposure (dpe), thereby confirming late virus
transmission from the inoculated pigs. Virus transmission to in-contact pigs
occurred at four weeks post-exposure, over three months after the primary
infection. These results highlight the potential role of survivor pigs in disease
maintenance and dissemination in areas where moderate- to low-virulent viruses
may be circulating undetected. This study will help design better and more
effective control programmes to fight against this disease.
PMID- 26432069
TI - Erratum to: The effect of vitamin D supplements on the severity of restless legs
syndrome.
PMID- 26432071
TI - A case of a perforated obturator hernia with a femoral abscess treated a
pectineus muscle flap.
AB - BACKGROUND: An obturator hernia accompanied with a femoral abscess is rare, and
leads to severe infection. Repeated draining is often required due to remnant
abscess. CASE PRESENTATION: We herein reported a case of a perforated obturator
hernia with a femoral abscess that was successfully treated via repair using the
pectineus muscle. An 84-year-old Japanese woman was referred to our hospital with
appetite loss and right femoral pain. Abdominal computed tomography (CT) revealed
a right obturator hernia and abscess spreading to the right thigh. Emergency
surgery was performed. Intraoperative findings revealed that the abscess had
formed because of a perforation in the small intestine by an incarcerated
obturator hernia. We performed partial resection of the small intestine, repaired
the hernial orifice, drained the right femoral abscess, and filled the cavity
using the pectineus muscle. A residual abscess was not detectable following
surgery, and the patient was discharged on postoperative day 63. CONCLUSION: Some
patients with a perforated obturator hernia and femoral abscess have a residual
abscess following surgery that requires redrainage. Nevertheless, we consider it
possible to successfully treat a perforated obturator hernia with a femoral
abscess via repair using the pectineus muscle.
PMID- 26432070
TI - Improved long-term autonomic function following resolution of sleep-disordered
breathing in preschool-aged children.
AB - PURPOSE: Sleep-disordered breathing (SDB) prevalence peaks in preschool children
and is associated with deficits in cardiovascular functioning during sleep. No
long-term studies have investigated the effects of SDB resolution in mitigating
these outcomes. We hypothesized that following 3 years, normalization of
alterations to heart rate (HR), pulse transit time (PTT), heart rate variability
(HRV), and urinary catecholamines identified at the initial diagnosis would be
associated with resolution of SDB. METHODS: Forty-five children with SDB and 28
non-snoring controls underwent polysomnography at baseline (3-5 years) and follow
up (6-9 years). Children were classified into control, resolved, and unresolved
SDB. Resolution was defined as an obstructive apnea-hypopnea index (OAHI) <=1
event/h, no snoring on polysomnography (PSG), or indicated by parents. PTT is an
inverse surrogate measure of blood pressure change. HRV was assessed using power
spectral analysis. RESULTS: There was no change in PTT or HR between studies for
any group. Our HRV data suggest reduced parasympathetic activity in children
whose SDB resolved and increased parasympathetic activity in children whose SDB
remained the same or worsened at follow-up. We identified a significant
correlation between low frequency power and urinary dopamine and adrenaline
levels at follow-up in the unresolved group, suggesting increased sympathetic
activity in children with unresolved SDB. CONCLUSION: Our findings suggest an
association between resolution of SDB and normalization of HRV in the long term
in these preschool children and an augmented sympathetic activity in the children
with residual SDB. This highlights the autonomic impact of SDB in young children
and the importance of detection and treatment.
PMID- 26432072
TI - Clinical and Imaging Follow-up Practices after Transarterial Therapy for Primary
and Secondary Hepatic Malignancies: Results of an Online Survey.
AB - RATIONALE AND OBJECTIVES: To characterize practices and quantify variation in
longitudinal follow-up approaches among interventional radiologists (IRs) after
liver transarterial locoregional therapy (LRT) in contemporary Interventional
Oncology practice. MATERIALS AND METHODS: In November/December 2014, Society of
Interventional Radiology members were invited to participate in a survey
regarding clinical and imaging follow-up of liver cancer patients treated with
transarterial LRT. On survey closure, responses were compiled and analyzed.
RESULTS: The 30-item survey response rate was 11% (361 of 3290). Respondents were
predominantly American IRs (311 of 355, 88%) who perform 1-5 LRTs monthly (196 of
354, 55%). Most (305 of 336, 91%) IRs reported longitudinal follow-up, with
patient encounters within 1-month (73%, 211 of 290) postprocedure and every 3
months (68%, 196 of 287) thereafter and involvement in imaging (up to 80%, 235 of
290) ordering and evaluation. Preferred timing of first follow-up imaging (1
month vs. 3 months) and response criteria used (mRECIST favored) varied.
CONCLUSIONS: Although IRs are actively involved in clinical and imaging follow-up
of patients with liver malignancies treated with transarterial LRTs, there are
differences in imaging frequency and response assessment. These data may serve as
a starting point for standardization of LRT follow-up.
PMID- 26432073
TI - 70-kVp High-pitch Computed Tomography Pulmonary Angiography with 40 mL Contrast
Agent: Initial Experience.
AB - RATIONALE AND OBJECTIVES: To assess image quality, radiation dose, and diagnostic
accuracy of 70-kVp high-pitch computed tomography pulmonary angiography (CTPA)
using 40 mL contrast agent and sinogram affirmed iterative reconstruction
(SAFIRE) compared to 100-kVp CTPA using 60 mL contrast agent and filtered back
projection. MATERIALS AND METHODS: Eighty patients underwent CTPA at either 70
kVp (group A, n = 40; 3.2 pitch, 40 mL contrast medium, and SAFIRE) or 100 kVp
(group B, n = 40; 1.2 pitch, 60 mL contrast medium, and filtered back
projection). Signal-to-noise ratio and contrast-to-noise ratio were calculated.
Subjective image quality was evaluated using a five-grade scale, and diagnostic
accuracy was assessed. Radiation doses were compared. RESULTS: Computed
tomography values, signal-to-noise ratio, and contrast-to-noise ratio of
pulmonary arteries were higher in group A compared to group B (all P < 0.001).
Subjective image quality showed no difference between the two groups (P = 0.559)
with good interobserver agreement (kappa = 0.647). No difference was found
regarding diagnostic accuracy between the two groups (P > 0.05). The effective
dose for group A was lower by 80% compared to group B (P < 0.001). CONCLUSIONS:
70-kVp high-pitch CTPA with reduced contrast media and SAFIRE provides comparable
image quality and substantial radiation dose savings compared to a routine CTPA
protocol.
PMID- 26432074
TI - Increasing aclarubicin dosage of the conventional CAG (low-dose cytarabine and
aclarubicin in combination with granulocyte colony-stimulating factor) regimen is
more efficacious as a salvage therapy than CAG for relapsed/refractory acute
myeloid leukemia.
AB - The efficacy and safety of a modified CAG (low-dose cytarabine and aclarubicin in
combination with granulocyte colony-stimulating factor) regimen with an increased
aclarubicin dosage [high-dose (HD)-CAG] were observed in 145 patients with
relapsed/refractory (R/R) acute myeloid leukemia (AML) and compared to the
results of 172 patients treated with a conventional CAG regimen. The HD-CAG
regimen showed both a higher complete remission (CR) rate (60.7% vs. 46.5%,
P=0.013) and overall response (OR) rate (74.5% vs. 63.4%, P=0.039) than CAG. For
patients aged <60 years, HD-CAG manifested an efficacy advantage over the CAG
regimen (62.6% vs. 47.4%, P=0.015). The 4-year overall survival (OS) rate was
30.3%+/-13.2% with a median survival time of 19.0+/-5.4 months for patients re
induced with the HD-CAG regimen, which showed no significant difference compared
to the CAG regimen (with a 4-year OS rate of 18.2%+/-5.3% and a median survival
time of 16.0+/-3.6 months, P=0.485). The main adverse effect was
myelosuppression; platelet recovery over 50*10(9)/L was extended by the HD-CAG
regimen (15 days vs. 10 days of the CAG regimen, P=0.003), which was tolerable
and manageable. HD-CAG can safely improve efficacy compared to the CAG regimen
and thus serves as an alternative treatment for R/R AML.
PMID- 26432075
TI - Dissecting estimation of conductances in subthreshold regimes.
AB - We study the influence of subthreshold activity in the estimation of synaptic
conductances. It is known that differences between actual conductances and the
estimated ones using linear regression methods can be huge in spiking regimes, so
caution has been taken to remove spiking activity from experimental data before
proceeding to linear estimation. However, not much attention has been paid to the
influence of ionic currents active in the non-spiking regime where such linear
methods are still profusely used. In this paper, we use conductance-based models
to test this influence using several representative mechanisms to induce ionic
subthreshold activity. In all the cases, we show that the currents activated
during subthreshold activity can lead to significant errors when estimating
synaptic conductance linearly. Thus, our results add a new warning message when
extracting conductance traces from intracellular recordings and the conclusions
concerning neuronal activity that can be drawn from them. Additionally, we
present, as a proof of concept, an alternative method that takes into account the
main nonlinear effects of specific ionic subthreshold currents. This method,
based on the quadratization of the subthreshold dynamics, allows us to reduce the
relative errors of the estimated conductances by more than one order of
magnitude. In experimental conditions, under appropriate fitting to canonical
models, it could be useful to obtain better estimations as well even under the
presence of noise.
PMID- 26432076
TI - Combination therapy for multidrug-resistant cytomegalovirus disease.
AB - Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses
to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who
underwent allogeneic hematopoietic stem cell transplantation from a CMV
seronegative donor. Experimental treatments using leflunomide and artesunate
failed. Re-transplantation from a CMV-seropositive donor supported by adoptive
transfer of pp65-specific T cells and maribavir was followed by lasting
suppression. This case illustrates that successful MDR CMV therapy may require
individualized multidisciplinary approaches.
PMID- 26432077
TI - Meaning is Not a Reflex: Context Dependence of Spatial Congruity Effects.
AB - In two experiments, Brookshire, Ivry, and Casasanto (2010) showed that words with
positive and negative emotional valence can activate spatial representations with
a high degree of automaticity, but also that this activation is highly context
dependent. Lebois, Wilson-Mendenhall, and Barsalou (2015) reported that they
"aimed to replicate" our study but found only null results in the "Brookshire et
al. replication" conditions. Here we express concerns about three aspects of this
paper. First, the study was not an attempt to replicate ours; it was a different
study that adapted our method. Second, Lebois et al. did not accurately represent
our theoretical position. Third, Lebois et al.'s main conclusion, that spatial
congruity effects depend on the task context, was not supported by their data.
Despite these concerns, we agree with Lebois et al.'s overall message that
spatial aspects of words' meanings are activated differently in different
contexts. This was a main conclusion of our study as well.
PMID- 26432078
TI - Capybara Bites: Report of Human Injury Caused by a Hydrochoerus hydrochaeris.
AB - BACKGROUND: Health care demand due to animal bites is frequent, especially in the
emergency department (ED). In addition to the physical trauma caused by bites,
one should be concerned with infectious diseases that can be transmitted. The
range of the lesions depends on the animal species. Bites of Hydrochoerus
hydrochaeris (capybaras) in humans are relatively uncommon. Capybaras are docile
animals; however, their large rodent incisive teeth could cause serious injury.
Localized care, antibiotic therapy when necessary, careful examination of the
structures, tetanus and rabies immunization as indicated, and follow-up are
recommended for wild animal bites. The authors hereby describe and discuss the
medical management of a case of multiple lesions from capybara bites on the right
thigh of a man. CASE REPORT: A 54-year-old male patient was admitted to the ED
with a compression bandage soaked with blood after being bitten by a capybara. At
the clinical examination, the patient had two lacerating wounds and multiple
abrasions on the anterior face of the right thigh. Rabies prophylaxis was
administered and the wounds were irrigated and closed with sterile dressings.
Oral amoxicillin/clavulanate potassium for 7 days was administered to the
patient. The patient was followed up; 3 months after the attack he returned to
his previous level of activity without any complication. WHY SHOULD AN EMERGENCY
PHYSICIAN BE AWARE OF THIS?: We recommend that practitioners and physicians
should provide prompt attention due to potentially significant morbidities,
particularly rabies. The adequate care of the wound will allow better aesthetic
and functional results to victims of wild animal bites.
PMID- 26432079
TI - Diabetic Ketoacidosis Precipitated by Urachal Cyst Infection.
PMID- 26432080
TI - Tracheal Intubation with a McGrath(r) Series 5 Video Laryngoscope by Novice
Personnel in a Cervical-immobilized Manikin.
AB - BACKGROUND: Prehospital tracheal intubation may be performed by novice intubators
in cervical immobilized patients. However, most indirect laryngoscopes require
special training. The McGrath(r) Series 5 video laryngoscope is similar to the
Macintosh laryngoscope in shape and usage, yet still confers the advantages of
having indirect laryngoscopes. OBJECTIVE: This study compared tracheal intubation
by novice users, using the McGrath(r) Series 5 video laryngoscope vs. the
Macintosh laryngoscope in a cervical immobilized manikin. METHODS: Thirty-eight
nurses intubated the trachea of a manikin using a McGrath(r) Series 5 video
laryngoscope and a Macintosh laryngoscope, in random order. Then they repeated
the procedure in a manikin with a cervical collar. Success rate, time to success,
number of intubation attempts, dental clicks, and difficulty score were compared
between the two laryngoscopes. RESULTS: First-attempt success rate was higher for
the McGrath(r) Series 5 compared to the Macintosh laryngoscope in cervical
immobilizations (84.2% vs. 47.7%, respectively; p = 0.019). However, overall
intubation success rate with and without the cervical collar was no different.
Tracheal intubation using the McGrath(r) Series 5 was faster than the Macintosh
laryngoscope regardless of the presence of a cervical collar. McGrath(r) Series 5
required fewer trials, had fewer dental clicks, and was easier to use than the
Macintosh laryngoscope. CONCLUSIONS: McGrath(r) Series 5 video laryngoscope may
be better than a standard Macintosh laryngoscope for novice intubators intubating
the trachea in cervical immobilization, due to the higher first-attempt success
rate, faster intubation time, fewer dental clicks, lower number of intubation
attempts, and overall ease of use.
PMID- 26432081
TI - High Body Mass Index is Strongly Correlated with Decreased Image Quality in
Focused Bedside Echocardiography.
AB - BACKGROUND: There is a well-established relationship between obesity, as measured
by body mass index (BMI), and overall health risk. The presence of body fat is a
known limitation to ultrasound, but it is unknown whether any decrease in quality
due to obesity limits the interpretability of focused bedside echocardiography
(FBE). OBJECTIVES: To correlate obesity, as measured by BMI, with image quality
and interpretability of (FBE) performed by an emergency physician. METHODS: We
conducted a prospective observational study in a convenience sample of adults
presenting to two academic emergency departments (EDs) and a bariatric surgery
outpatient clinic. Twenty patients were enrolled in each of three BMI categories,
<30, 30-39, and >=40 kg/m(2). FBE was performed in multiple views in two
positions. Images were rated for ability to discern the pericardial myocardial
interface (PMI) and the endocardial border of the left ventricle (ELV). RESULTS:
There were 23 males and 37 females enrolled. The median age was 49 years and the
median BMI was 35.6 kg/m(2). There was a significant difference in the percentage
of technically limited examinations between BMI categories for both PMI and ELV.
There was an overall negative linear correlation between BMI and image quality
for both PMI and ELV. CONCLUSION: There is an overall decrease in the quality of
focused bedside echocardiographic images as BMI increases. This relationship
exists for visualization of both the PMI and the ELV. Emergency physicians should
be aware of the potential limitations of focused bedside echocardiography in this
patient population.
PMID- 26432082
TI - Giant Right Coronary Artery Aneurysm Masquerading as a Pulmonary Embolus.
PMID- 26432083
TI - Identification of Peroneal Tenosynovitis by Point-of-Care Ultrasonography.
AB - BACKGROUND: Ankle pain is a frequent chief complaint, and although peroneal
tendon disorders are relatively uncommon, if treated inappropriately they may
cause persistent pain and dysfunction. Peroneal tendon disorders, including the
tendon sheath inflammatory condition tenosynovitis, are a major cause of chronic
lateral ankle pain. Although magnetic resonance imaging has emerged as the
modality of choice to assess the majority of these injuries, dynamic
ultrasonography detects tendon pathology such as tenosynovitis. CASE REPORT: A 69
year-old woman presented to the Emergency Department (ED) after several months of
atraumatic, progressive right foot and ankle pain. On physical examination, she
had swelling and point tenderness posterior and inferior to the lateral
malleolus, which was exacerbated by eversion. Plain radiography of the foot and
ankle showed only soft tissue swelling. Bedside ultrasonography performed by the
emergency physician quickly identified findings consistent with peroneal
tenosynovitis without tears. Management with a walking boot and nonsteroidal
antiinflammatory drugs was initiated prior to discharge. WHY SHOULD AN EMERGENCY
PHYSICIAN BE AWARE OF THIS?: In this case of peroneal tenosynovitis, point-of
care ultrasonography was used to promptly and accurately identify hyperemia,
synovial thickening, and a marked effusion within the right peroneal tendon
sheath. Nonoperative treatment of tenosynovitis was initiated in the ED while
findings were subsequently confirmed with magnetic resonance imaging. Emergency
physicians should be aware of the utility of identifying tenosynovitis by point
of-care ultrasonography, which can expedite nonoperative management and prevent
long-term complications.
PMID- 26432084
TI - Ventriculoperitoneal Shunt Failure Presenting as Isolated Unilateral Abducens
Nerve Palsy.
PMID- 26432085
TI - Unusual Complication of a Central Venous Catheter in a Thoracoabdominal Trauma.
PMID- 26432086
TI - In Reply to: Unusual Complication of a Central Venous Catheter in a
Thoracoabdominal Trauma.
PMID- 26432087
TI - The impact of glutathione S-transferase genotype and phenotype on the adverse
drug reactions to azathioprine in patients with inflammatory bowel diseases.
AB - Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with
inflammatory bowel disease (IBD). However, the use is limited in one-third of
patients because of adverse drug reactions (ADRs) or a lack of clinical response.
It has been considered that the polymorphic enzyme thiopurine S-methyltransferase
(TPMT) plays an important role in the in vivo process of AZA and the occurrence
of its myelotoxicity. Glutathione S-transferase (GST) mutation is another
pharmacogenetic polymorphism which is probably involved in AZA metabolism and
tolerance. The aim of this study was to investigate the association among GST
polymorphism, enzyme activity and AZA-related ADRs in Chinese Han patients with
IBD. We found that the patients who became neutropenic had a significantly higher
GSTs activity when compared with of the patients who did not develop ADRs
(analysis of variance, P < 0.001). There was also a significant
underrepresentation of GSTP1*-105V allele among patients developing ADRs (odds
ratio [OR] = 0.125, 95% confidence interval [CI] = 0.022-0.709, P = 0.0012). The
patients with higher GST activity constituted a pharmacogenetic high risk group
for leucopenia during AZA treatment. GST-P1 Ile105/Ile105 genotype appeared to be
a promising marker indicating predisposition to AZA-related ADRs.
PMID- 26432088
TI - Spontaneous baroreceptor reflex sensitivity for risk stratification of heart
failure patients: optimal cut-off and age effects.
AB - Baroreceptor reflex sensitivity (BRS) is an important prognostic factor because a
reduced BRS has been associated with an adverse cardiovascular outcome. The
threshold for a 'reduced' BRS was established by the ATRAMI study at BRS <3
ms/mmHg in patients with a previous myocardial infarction, and has been shown to
improve risk assessment in many other cardiac dysfunctions. The successful
application of this cut-off to other populations suggests that it may reflect an
inherent property of baroreflex functioning, so our goal is to investigate
whether it represents a 'natural' partition of BRS values. As reduced baroreflex
responsiveness is also associated with ageing, we investigated whether a BRS
estimate <3 ms/mmHg could be the result of a process of physiological senescence
as well as a sign of BRS dysfunction. This study involved 228 chronic heart
failure patients and 60 age-matched controls. Our novel method combined transfer
function BRS estimation and automatic clustering of BRS probability
distributions, to define indicative levels of different BRS activities. The
analysis produced a fit clustering (cophenetic correlation coefficient 0.9 out of
1) and identified one group of homogeneous patients (well separated from the
others by 3 ms/mmHg) with an increased BRS-based mortality risk [hazard ratio
(HR): 3.19 (1.73, 5.89), P<0.001]. The age-dependent BRS cut-off, estimated by 5%
quantile regression of log (BRS) with age (considering the age-matched controls),
provides a similar mortality value [HR: 2.44 (1.37, 4.43), P=0.003]. In
conclusion, the 3 ms/mmHg cut-off identifies two large clusters of homogeneous
heart failure (HF) patients, thus supporting the hypothesis of a natural cut-off
in the HF population. Furthermore, age was found to have no statistical impact on
risk assessment, suggesting that there is no need to establish age-based cut-offs
because 3 ms/mmHg optimally identifies patients at high mortality risk.
PMID- 26432089
TI - [Resistant fungi].
AB - Particularly in the area of hematology/oncology and intensive care medicine,
infections due to resistant fungi are to be expected. Emergence of resistance in
fungi is a less dynamic process than in bacteria; it can, however, have an
equally important impact on treatment strategies. In the following article, the
most important resistance patterns of yeasts and molds (Candida albicans ,
Aspergillus fumigatus, the order Mucorales and the genus Fusarium) will be
presented and discussed. Their diagnosis mostly being based on blood cultures,
resistance testing for yeasts is usually readily available. Culture-based
therapeutic adjustments in mold infections are, however, only rarely possible, as
most antifungal therapies for these infections are initiated on an empirical
basis after identification of typical infiltrates on a CT scan. Response to
therapy is then evaluated on the basis of clinical signs and symptoms in
combination with follow-up CT scans. In case of therapeutic failure or appearance
of suspicious infiltrates under antifungal prophylaxis, an open or CT-guided
biopsy is recommended to allow efficient adaptation of antifungal treatment. In
individual cases, particularly in patients diagnosed with mucormycosis, resection
of the focus of infection may be necessary to achieve a satisfactory treatment
response.
PMID- 26432090
TI - Employing transposon mutagenesis to investigate foot-and-mouth disease virus
replication.
AB - Probing the molecular interactions within the foot-and-mouth disease virus (FMDV)
RNA replication complex has been restricted in part by the lack of suitable
reagents. Random insertional mutagenesis has proven an excellent method to reveal
domains of proteins essential for virus replication as well as locations that can
tolerate small genetic insertions. Such insertion sites can subsequently be
adapted by the incorporation of commonly used epitope tags, facilitating their
detection with commercially available reagents. In this study, we used random
transposon-mediated mutagenesis to produce a library of 15 nt insertions in the
FMDV nonstructural polyprotein. Using a replicon-based assay, we isolated
multiple replication-competent as well as replication-defective insertions. We
adapted the replication-competent insertion sites for the successful
incorporation of epitope tags within FMDV non-structural proteins for use in a
variety of downstream assays. Additionally, we showed that replication of some of
the replication-defective insertion mutants could be rescued by co-transfection
of a 'helper' replicon, demonstrating a novel use of random mutagenesis to
identify intergenomic trans-complementation. Both the epitope tags and
replication-defective insertions identified here will be valuable tools for
probing interactions within picornavirus replication complexes.
PMID- 26432091
TI - Efficacy of skin closure with subcuticular sutures for preventing wound infection
after resection of colorectal cancer: a propensity score-matched analysis.
AB - PURPOSE: The purpose of this study was to examine the efficacy of skin closure
with subcuticular sutures for the prevention of wound infection after colorectal
cancer resection. METHODS: Medical records of 1008 patients with colorectal
cancer who underwent resection between 2006 and 2013 were reviewed. Patients were
divided into two groups based on skin closure method: the subcuticular suture
group (n = 323) and the staple group (n = 685). The incidence of wound infection
was compared with and without propensity score matching, and multivariate
analysis was performed to identify risk factors for wound infection. RESULTS: The
incidence of wound infection was 3.1 % (10/323) in the subcuticular suture group
and 10.4 % (71/685) in the staple group. After propensity score matching, the
incidence of wound infection was significantly lower in the subcuticular suture
group (4.6 %, 9/197) than in the staple group (12.2 %, 24/197) (p = 0.004). In
the propensity score-matched cohort, multivariate analysis identified advanced
age (odds ratio [OR], 1.07; 95 % confidence interval [CI], 1.03-1.12), higher
preoperative body mass index (OR, 1.19; 95 % CI, 1.07-1.33), lower preoperative
serum albumin (OR, 0.45; 95 % CI, 0.22-0.91), open surgery (OR, 3.28; 95 % CI,
1.38-8.49), and skin closure with staples (OR, 3.21; 95 % CI, 1.43-7.81) as
independent risk factors for wound infection. CONCLUSIONS: Our results suggest
that subcuticular suturing could be beneficial after colorectal cancer surgery.
PMID- 26432092
TI - Novel Therapies in IBS-D Treatment.
AB - OPINION STATEMENT: Irritable bowel syndrome (IBS) is a common gastrointestinal
disease characterized by abdominal pain and change in bowel habits. IBS diarrhea
predominant (IBS-D), which is arguably the most common subset of IBS, is also
associated with rectal urgency, increased frequency, abdominal bloating, and
loose to watery stools. Current treatments for diarrhea include mu-opioid
agonists (i.e., loperamide, lomotil) and bile acid sequestrants (i.e.,
cholestyramine) while treatments for abdominal pain include antispasmodics (i.e.,
hyoscyamine, dicyclomine) and tricyclic antidepressants (i.e., amitriptyline).
There are currently 3 FDA-approved treatments for IBS-D, which have been shown to
improve both abdominal pain and diarrhea. Alosetron was initially approved by FDA
2000; however, its use is now limited to women with severe IBS-D symptoms
refractory to other treatment. Eluxadoline, a mixed mu-opioid agonist, and
rifaximin, a broad spectrum gut specific antibiotic, were both FDA approved in
2015. Eluxadoline has been shown to relieve abdominal pain and stool consistency
in appropriate candidates. While large trials already showed the efficacy of
rifaximin in treating non-constipated IBS for bloating, stool consistency, and
abdominal pain, the recent TARGET 3 trial demonstrates that retreatment is also
effective. While these new treatments significantly expand options for patients
suffering from IBS-D, there is likely to remain a need for additional safe and
effective therapies.
PMID- 26432093
TI - Development and psychometric evaluation of a new patient -reported outcome
measure for stroke self -management: The Southampton Stroke Self - Management
Questionnaire (SSSMQ).
AB - BACKGROUND: Self-management is important to the recovery and quality of life of
people following stroke. Many interventions to support self-management following
stroke have been developed, however to date no reliable and valid outcome measure
exists to support their evaluation. This study outlines the development and
preliminary investigation of the psychometric performance of a newly developed
patient-reported outcome measure (PROM) of self-management competency following
stroke; the Southampton Stroke Self-Management Questionnaire (SSSMQ). METHODS: A
convenience sample of 87 people who had had a stroke completed responses to the
SSSMQ, the Stroke Self-Efficacy Questionnaire and the Stroke Impact Scale.
Scaling properties were assessed using Mokken Scale Analysis. Reliability and
construct validity were assessed using intra-class correlation coefficient (ICC),
Mokken and Cronbach's reliability coefficients and Spearman rank order
correlations with relevant measures. RESULTS: Mokken scaling refined the SSSMQ to
28 scalable items. Internal consistency reliability (Mokken r = 0.89) and test
retest reliability (ICC = 0.928) were excellent. Hypotheses of expected
correlations with additional measures held, demonstrating good evidence for
construct validity. CONCLUSIONS: Early findings suggest the Southampton Stroke
Self-Management Questionnaire is a reliable and valid scale of self-management
competency. The SSSMQ represents a potentially valid PROM for the evaluation of
self-management following stroke.
PMID- 26432095
TI - Metagenome-wide Association Studies Potentiate Precision Medicine for Rheumatoid
Arthritis.
PMID- 26432094
TI - Applications of Next-generation Sequencing in Systemic Autoimmune Diseases.
AB - Systemic autoimmune diseases are a group of heterogeneous disorders caused by
both genetic and environmental factors. Although numerous causal genes have been
identified by genome-wide association studies (GWAS), these susceptibility genes
are correlated to a relatively low disease risk, indicating that environmental
factors also play an important role in the pathogenesis of disease. The
intestinal microbiome, as the main symbiotic ecosystem between the host and host
associated microorganisms, has been demonstrated to regulate the development of
the body's immune system and is likely related to genetic mutations in systemic
autoimmune diseases. Next-generation sequencing (NGS) technology, with high
throughput capacity and accuracy, provides a powerful tool to discover genomic
mutations, abnormal transcription and intestinal microbiome identification for
autoimmune diseases. In this review, we briefly outlined the applications of NGS
in systemic autoimmune diseases. This review may provide a reference for future
studies in the pathogenesis of systemic autoimmune diseases.
PMID- 26432096
TI - Modulation of risk/reward decision making by dopaminergic transmission within the
basolateral amygdala.
AB - RATIONALE: Dopamine (DA) transmission within cortico-limbic-striatal circuitry is
integral in modulating decisions involving reward uncertainty. The basolateral
amygdala (BLA) also plays a role in these processes, yet how DA transmission
within this nucleus regulates cost/benefit decision making is unknown.
OBJECTIVES: We investigated the contribution of DA transmission within the BLA to
risk/reward decision making assessed with a probabilistic discounting task.
METHODS: Rats were well-trained to choose between a small/certain reward and a
large/risky reward, with the probability of obtaining the larger reward
decreasing (100-12.5 %) or increasing (12.5-100 %) over a session. We examined
the effects of antagonizing BLA D1 (SCH 23390, 0.1-1 MUg) or D2 (eticlopride, 0.1
1 MUg) receptors, as well as intra-BLA infusions of agonists for D1 (SKF 81297,
0.1-1 MUg) and D2 (quinpirole, 1-10 MUg) receptors. We also assessed how DA
receptor stimulation may induce differential effects related to baseline levels
of risky choice. RESULTS: BLA D1 receptor antagonism reduced risky choice by
decreasing reward sensitivity, whereas D2 antagonism did not affect overall
choice patterns. Stimulation of BLA D1 receptors optimized decision making in a
baseline-dependent manner: in risk-averse rats, infusions of a lower dose of
SKF81297 increased risky choice when reward probabilities were high (50 %),
whereas in risk-prone rats, this drug reduced risky choice when probabilities
were low (12.5 %). Quinpirole reduced risky choice in risk-prone rats, enhancing
lose-shift behavior. CONCLUSIONS: These data highlight previously uncharacterized
roles for BLA DA D1 and D2 receptors in biasing choice during risk/reward
decision making through mediation of reward/negative feedback sensitivity.
PMID- 26432097
TI - Transplantation of human Wharton's jelly-derived mesenchymal stem cells highly
expressing TGFbeta receptors in a rabbit model of disc degeneration.
AB - INTRODUCTION: Mesenchymal stem cells (MSCs) are widely considered to hold promise
for the treatment of intervertebral disc (IVD) degeneration. However, variation
in the therapeutic efficacy of MSCs is a major problem and the derivation of MSCs
for use in IVD regeneration has not been optimized. Additionally, no data are
available on the efficacy of Wharton's Jelly-derived MSC (WJ-MSC) transplantation
in an animal model of IVD degeneration. METHODS: This study evaluated the
effectiveness of a cross-linked hyaluronic acid (XHA) scaffold loaded with human
WJ-MSCs, according to their expression levels of transforming growth factor-beta
receptor I/activin-like kinase receptor 5 (TbetaRI/ALK5) and TbetaRII, for IVD
regeneration in a rabbit model. We compared the degree of IVD regeneration
between rabbits transplanted with a XHA scaffold loaded with WJ-MSCs highly and
lowly expressing TbetaRI/ALK5 and TbetaRII (MSC-highTR and MSC-lowTR,
respectively) using magnetic resonance imaging (MRI) and histological analysis.
RESULTS: At 12 weeks after transplantation, T2-weighted MRI analysis showed
significant restoration of the disc water content in rabbits treated with a MSC
highTR-loaded XHA scaffold in comparison to rabbits treated with the scaffold
alone or a MSC-lowTR-loaded XHA scaffold. In addition, morphological and
histological analyses revealed that IVD regeneration was highest in rabbits
transplanted with a MSC-highTR-loaded XHA scaffold. CONCLUSION: Taken together,
our results suggest that a MSC-highTR-loaded XHA scaffold supports IVD
regeneration more effectively than a MSC-lowTR-loaded XHA scaffold. This study
supports the potential clinical use of MSC-highTR-loaded XHA scaffolds to halt
IVD degeneration or to enhance IVD regeneration.
PMID- 26432098
TI - Imaging of lumbar spinal surgery complications.
AB - Lumbar spine surgery for spinal stenosis is a frequently performed procedure and
was the fastest growing type of surgery in the US from 1980 to 2000. With
increasing surgical invasiveness, postoperative complications also tend to be
higher. Cross-sectional imaging techniques (CT and MRI) are more sensitive than
radiographs and play an increasingly important role in evaluation of patients
with lumbar spine surgery. Their use in patients with metallic implants is
somewhat limited by artefacts, which can obscure pathology and decrease accuracy
and reader confidence. Metal artefact reduction techniques have been developed,
which can significantly improve image quality and enable early detection of
postoperative complications. Complications can occur throughout postoperative
course. Early complications include hardware displacement, incidental durotomy,
postoperative collections-most commonly seroma, and less likely haematoma and/or
infection. Incidental durotomy with CSF leak causing intracranial hypotension has
characteristic MR brain findings and diagnosis of occult leak sites have been
improved with use of dynamic CT myelography. Haematomas, even when compressing
the thecal sac, are usually asymptomatic. Early infection, with nonspecific MR
findings, can be diagnosed accurately using dual radiotracer studies. Delayed
complications include loosening, hardware failure, symptomatic new or recurrent
disc herniation, peri-/epidural fibrosis, arachnoiditis, and radiculitis.
TEACHING POINTS: * CT and MRI play an increasingly important role in evaluation
of patients with lumbar spine surgery * Complications can occur throughout the
postoperative course and early detection is critical * Artefact reduction
techniques can improve image quality for early and improved detection of
complications.
PMID- 26432099
TI - Differentiating the bipolar disorders from borderline personality disorder.
AB - OBJECTIVE: To identify features differentiating bipolar disorder (BP) from
borderline personality disorder (BPD) and with each condition variably defined.
METHOD: Participants were assigned a BP or BPD diagnosis on the basis of DSM
criteria and, separately, by clinical judgment, and undertook a diagnostic
interview and completed self-report measures. RESULTS: Predictors of BPD status
varied according to diagnostic decisions, but with the most consistent items
being childhood sexual abuse, childhood depersonalization, personality variables
relating to relationship difficulties and sensitivity to criticism, and the
absence of any BP family history. Across diagnostic groups, personality measure
items alone predicted diagnostic allocation with an accuracy of 81-84%, the
refined study variables other than hypo/manic features improved the
classification rates to 88%, and when the presence or absence of hypo/manic
features was added, classification rates increased to 92-95%. CONCLUSION: Study
findings indicate that BPD can be differentiated from BP with a high degree of
accuracy.
PMID- 26432100
TI - Neurosteroids; potential underpinning roles in maintaining homeostasis.
AB - The neuroactive steroids which are synthesized in the brain and nervous system
are known as "Neurosteroids". These steroids have crucial functions such as
contributing to the myelination and organization of the brain connectivity. Under
the stressful circumstances, the concentrations of neurosteroid products such as
allopregnanolone (ALLO) and allotetrahydrodeoxycorticosterone (THDOC) alter. It
has been suggested that these stress-derived neurosteroids modulate the
physiological response to stress. Moreover, it has been demonstrated that the
hypothalamic-pituitary-adrenal (HPA) axis mediates the physiological adaptation
following stress in order to maintain homeostasis. Although several regulatory
pathways have been introduced, the exact role of neurosteroids in controlling HPA
axis is not clear to date. In this review, we intend to discern specific pathways
associated with regulation of HPA axis in which neuroactive steroids have the
main role. In this respect, we propose pathways that may be initiated after
neurosteroidogenesis in different brain subregions following acute stress which
are potentially capable of activating or inhibiting the HPA axis.
PMID- 26432102
TI - Monitor launches inquiry after NHS trust ran up L29.5m deficit in five months.
PMID- 26432101
TI - Characterization and expression analysis of adipokinetic hormone and its receptor
in eusocial aphid Pseudoregma bambucicola.
AB - Aphids display an extraordinary phenotypic plasticity ranging from widespread
reproductive and wing polyphenisms to the occurrence of sterile or subfertile
soldier morphs restricted to eusocial species of the subfamilies Eriosomatinae
and Hormaphidinae. Individual morphs are specialized by their behavior, anatomy,
and physiology to perform different roles in aphid societies at different stages
of the life cycle. The capacity of the insects to cope with environmental
stressors is under the control of a group of neuropeptides of the adipokinetic
hormone/red pigment-concentrating hormone family (AKH/RPCH) that bind to a
specific receptor (AKHR). Here, we describe the molecular characteristics of AKH
and AKHR in the eusocial aphid Pseudoregma bambucicola. The sequence of the
bioactive AKH decapeptide and the intron position in P. bambucicola AKH
preprohormone were found to be identical to those in a phylogenetically distant
aphid Dreyfusia spp. (Adelgidae). We detected four transcript variants of AKHR
that are translated into three protein isoforms. Further, we analyzed AKH/AKHR
expression in different tissues and insects of different castes. In wingless
females, a remarkable amount of AKH mRNA was only expressed in the heads. In
contrast, AKHR transcript levels increased in the order gutCT) in intron 13 of the albumin gene. The second patient had an
acquired alteration with a drift of albumin mobility to the anode. This severely
ill patient was on intra venous antibiotics and electrospray TOF MS showed a
stuttered repetition of the 66,439/66,558Da albumin isoforms at multiples of 455
459Da corresponding to the covalent attachment of 1, 2, 3 and 4 molecules of
flucloxacillin. This modification of +455Da was also detected in a control on a
1g/day oral dose of flucloxacillin. CONCLUSION: Both aberrations were associated
with diminished albumin concentrations. The C-terminal truncation of Rugby Park
(albumin, 29g/l) likely interferes with receptor binding and albumin scavenging,
while the 20g/l albumin in the second patient was mostly due to renal disease. In
both cases electrospray TOF MS proved a rapid (5min) sensitive (0.2MUl plasma)
and highly informative way of analysing whole plasma or serum.
PMID- 26432107
TI - Desmoplastic Melanoma Carries High Mutation Burden.
AB - The first thorough sequencing of desmoplastic melanoma samples has shown that
these tumors carry a median of 62 mutations per megabase-among the highest known
for all cancers. The results suggest that patients may respond well to
immunotherapy, which relies on detecting differences between normal and cancerous
cells.
PMID- 26432109
TI - Surgical diversity and evolution in cataract and refractive surgery.
PMID- 26432108
TI - Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted
Therapy in MET-Amplified Esophagogastric Cancer.
AB - MET inhibition is effective in some patients with MET-amplified esophagogastric
cancer (EGC), but understanding acquired and de novo resistance mechanisms will
be critical to improving therapy. We identified KRAS mutation as a novel cause of
acquired resistance in a patient after a 2-year response to a MET inhibitor. We
also observed that 40% to 50% of patients with MET-amplified EGC harbor
coamplification of HER2 and/or EGFR concurrently in the same tumor cells, which
can drive de novo resistance. One patient with concurrent MET and HER2
amplification was refractory to HER2 blockade, but responded to combined MET/HER2
inhibition. We also found striking heterogeneity in MET amplification between
distinct metastatic lesions and primary tumors in individual patients with EGC.
In these patients, MET inhibition led to mixed responses and disease progression
through outgrowth of non-MET-amplified clones, which could be monitored in
circulating tumor DNA. Thus, receptor coamplification and molecular heterogeneity
may be key drivers of clinical resistance in MET-amplified EGC. SIGNIFICANCE:
Coamplification of driver oncogenes occurs frequently in EGC and can drive
therapeutic resistance, supporting a role for comprehensive molecular analysis
prior to targeted therapy. EGCs can also exhibit extensive heterogeneity in gene
amplification between distinct tumor lesions within the same patient, suggesting
that molecular profiling of a single-lesion biopsy may be insufficient to guide
targeted therapy selection.
PMID- 26432110
TI - New add-on intraocular lens for patients with age-related macular degeneration.
AB - We present a new option for visual rehabilitation of patients with advanced
macular degeneration and evaluate the outcomes in the first 8 patients who had
implantation of the ciliary sulcus-fixated macular add-on intraocular lens (IOL)
(Scharioth Macula Lens) at our institute. The surgical technique for implantation
of the add-on IOL is described. Near vision improved in 7 eyes and was stable in
1 eye. The corrected near visual acuity improved by 4.4 lines with the macular
add-on IOL at 15 cm versus with glasses at 40 cm; it improved by 2.1 lines with
the macular add-on IOL at 15 cm versus with glasses at 15 cm. Distance vision was
stable in all eyes. No intraoperative or postoperative complication occurred. The
macular add-on IOL has the potential of improving near vision and reading ability
in patients with advanced age-related macular degeneration. FINANCIAL DISCLOSURE:
Dr. Scharioth is a consultant to Alcon Laboratories, Inc., and Medicontur Ltd. He
is the inventor of the Scharioth Macula Lens and receives royalties.
PMID- 26432111
TI - Suture-guided capsular tension ring insertion to reduce risk for iatrogenic
zonular damage.
AB - The capsular tension ring (CTR) is a useful device for managing a zonular
dialysis. However, insertion of the CTR has potential complications. The CTR can
damage zonular fibers during deployment into the capsular bag. Also, the angle
and point of initial contact of the CTR with the capsular bag relative to the
orientation of the dialysis must be considered to avoid damage to the zonular
fibers. Adequate fill of the capsular bag with an ophthalmic viscosurgical device
is important to minimize the risk for capsule entanglement with the leading
eyelet of the CTR. A simple technique is described to prevent these
complications. The technique can be used with both standard and modified CTRs.
FINANCIAL DISCLOSURE: Dr. Page is a consultant to Bausch & Lomb, Inc. and Abbott
Medical Optics, Inc. He has no financial or proprietary interest in any material
or method mentioned.
PMID- 26432112
TI - Range of refractive independence and mechanism of action of a corneal shape
changing hydrogel inlay: results and theory.
AB - PURPOSE: To demonstrate the independence of visual performance over a range of
preoperative refraction and age in presbyopes implanted with a corneal shape
changing inlay (Raindrop Near Vision Inlay). SETTING: Two multispecialty clinics,
Monterrey and Tijuana, Mexico. DESIGN: Prospective case series. METHODS: The
nondominant eyes of patients were implanted with the hydrogel corneal inlay
beneath a femtosecond flap, centered on the pupil. Clinical outcomes included
uncorrected near, intermediate, and distance visual acuity (UNVA, UIVA, and UDVA)
and patient-assessed task performance in good light and dim light. Statistical
analyses assessed the dependencies on preoperative age (45 to 60 years) and
preoperative manifest refraction spherical equivalent (MRSE) (-0.5 to +1.5
diopters [D]). Using the inlay effect derived from wavefront measurements, an eye
model was created through which letter charts were simulated. RESULTS: The study
evaluated eyes of 188 patients. Postoperative UNVA, UIVA, and task performance at
these distances in good light was independent of age and preoperative MRSE (P >
.05). Postoperative UDVA was weakly dependent on preoperative MRSE, but distance
task performance in good light was not (P > .05). In the treated eye, the mean
postoperative UNVA was 20/25, UIVA was 20/25, and UDVA was 20/32. The clinical
outcomes are explained by consideration of zones within the pupil generating good
near, intermediate, and distance image quality. This was confirmed by visual
acuity simulations. CONCLUSIONS: The continuous center-near power profile induced
by the corneal shape-changing inlay provides good visual acuity and performance
from distance through near over a 2.0 D range of preoperative refraction and
presbyopic age. FINANCIAL DISCLOSURE: Drs. Steinert, Schwiegerling, Barragan
Garza, and Chayet are consultants to Revision Optics, Inc. Drs. Lang and Holliday
and Mr. Roy are employees of Revision Optics, Inc. Drs. Steinert, Schwiegerling,
Barragan-Garza, and Chayet have no financial or proprietary interest in any
material or method mentioned.
PMID- 26432113
TI - Corneal sensitivity after small-incision lenticule extraction and laser in situ
keratomileusis.
AB - PURPOSE: To longitudinally evaluate corneal sensitivity after small-incision
lenticule extraction and compare the results with those in previous studies.
SETTING: London Vision Clinic, London, United Kingdom. DESIGN: Retrospective case
series. METHODS: Consecutive myopic eyes treated with small-incision lenticule
extraction using the Visumax femtosecond laser were studied. Corneal sensitivity
was measured centrally and at 4 paracentral locations using a Cochet-Bonnet
esthesiometer preoperatively and 1 day, 1 week, and 1, 3, 6, and 12 months
postoperatively. Results were compared with averaged results from previous laser
in situ keratomileusis (LASIK) and small-incision lenticule extraction studies.
RESULTS: The mean spherical equivalent was -6.85 diopters (D) +/- 2.57 (SD). The
mean age was 36 +/- 11 years. After small-incision lenticule extraction, the
preoperative mean central corneal sensitivity dropped from 54 mm preoperatively
to 33 mm 1 day postoperatively, rising to 40 mm, 45 mm, 48 mm, 54 mm, and 55 mm
over 12 months; it reached baseline at 6 months (P > .05). For 21 LASIK studies,
the mean central corneal sensitivity dropped from 56 mm preoperatively to 6 mm at
1 day, rising to 14 mm, 23 mm, 34 mm, 45 mm, and 51 mm over 12 months. For 8
small-incision lenticule extraction studies, central corneal sensitivity dropped
from 57 mm preoperatively to 39 mm at 1 week, then rose to 39 mm, 42 mm, 49 mm,
52 mm, and 54 mm over 12 months; it was higher than after LASIK at 1 week and 1,
3, and 6 months (P < .05). CONCLUSION: Recovery of central corneal sensitivity to
baseline was reached by 6 months after small-incision lenticule extraction and
was higher than after LASIK for the first 6 months after surgery. FINANCIAL
DISCLOSURE: Dr. Reinstein is a consultant to Carl Zeiss Meditec AG, has a
proprietary interest in the Artemis technology (Arcscan, Inc.), and is an author
of patents related to very high-frequency digital ultrasound administered by the
Center for Technology Licensing at Cornell University, Ithaca, New York, USA. No
other author has a financial or proprietary interest in any material or method
mentioned.
PMID- 26432114
TI - Safety and efficacy of wavefront-guided myopic laser in situ keratomileusis using
a new wavefront sensor technology: first 100 cases.
AB - PURPOSE: To evaluate the safety and efficacy of wavefront-guided laser in situ
keratomileusis (LASIK) for the correction of low to high myopia and myopic
astigmatism using data derived from a new-generation Hartmann-Shack aberrometer.
SETTING: Refractive Surgery Unit, Bordeaux Hospital University, France. DESIGN:
Retrospective case series. METHODS: This retrospective study analyzed the initial
group of eyes treated with wavefront-guided LASIK for myopia and myopic
astigmatism using the Visx S4IR excimer laser and wavefront data derived from a
new Hartmann-Shack aberrometer (iDesign Advanced Wavescan aberrometer).
Refractive (refraction and refractive accuracy) and visual outcomes (uncorrected
[UDVA] and corrected [CDVA] distance visual acuities) were recorded 3 months
postoperatively. RESULTS: The study included 100 eyes of 50 consecutively treated
patients. The mean decimal UDVA improved from 0.1 +/- 0.1 (SD) preoperatively to
1.1 +/- 0.15 postoperatively (P < .01). A monocular UDVA of 20/16, 20/20, and
20/25 were achieved in 76.6%, 94.4%, and 96.6% of eyes, respectively. The
postoperative manifest spherical equivalent was within +/-0.5 diopter in all
eyes. No eye lost 2 or more lines of CDVA, and 29.2% of the eyes gained 1 or more
lines of CDVA. CONCLUSION: Wavefront-guided LASIK performed using data derived
from the new Hartmann-Shack aberrometer was safe, effective, and predictable for
treating myopia and myopic astigmatism. FINANCIAL DISCLOSURE: No author has a
financial or proprietary interest in any material or method mentioned.
PMID- 26432115
TI - Femtosecond-assisted laser in situ keratomileusis for consecutive hyperopia after
radial keratotomy.
AB - PURPOSE: To evaluate femtosecond-assisted laser in situ keratomileusis (LASIK)
for the treatment of hyperopic shift after radial keratotomy (RK). SETTING:
Private practice, Siena, Italy. DESIGN: Prospective case series. METHODS: Eyes
with a spherical equivalent (SE) of +1.0 diopters (D) to +4.0 D after RK with 6
or 8 incisions had LASIK. The flap (nominal thickness 130 MUm) was created with a
femtosecond laser (LDV Z2); the refractive ablation was performed with an excimer
laser (217P). The flap was dissected in a centrifugal fashion along previous RK
cuts. RESULTS: Eighteen eyes of 10 patients were treated. Preoperatively, the
mean defocus equivalent was 3.13 diopters (D) +/- 0.71 (SD); the corrected
distance visual acuity (CDVA) was 0.09 +/- 0.06 logMAR. At 9 months, the mean
defocus equivalent was 0.51 +/- 0.47 D (P < .05), with 13 eyes (72%) having 0.50
D or less of defocus equivalent and 16 eyes (89%) having 1.0 D or less of defocus
equivalent. The mean CDVA was 0.04 +/- 0.06 logMAR (P < .05). No lines of logMAR
CDVA were lost. The mean uncorrected distance visual acuity was 0.11 +/- 0.10
logMAR. The safety index was 1.11; the efficacy index was 0.97. No retreatments
were performed. Flap complications were limited to an RK incision opening larger
than 2 mm in 3 eyes and 1 case of a small, self-limiting epithelial ingrowth.
CONCLUSION: Laser in situ keratomileusis with a low-energy femtosecond laser was
a safe and effective approach to treat post-RK hyperopia, causing no relevant
inflammation. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary
interest in any material or method mentioned.
PMID- 26432116
TI - Hyperopic laser in situ keratomileusis: comparison of femtosecond laser and
mechanical microkeratome flap creation.
AB - PURPOSE: To evaluate and compare the refractive predictability and stability of
laser in situ keratomileusis (LASIK) flap creation performed with a femtosecond
laser and with a mechanical microkeratome to correct mild to moderate hyperopia.
SETTING: American University of Beirut Medical Center, Beirut, Lebanon. DESIGN:
Retrospective case series. METHODS: Patients who had hyperopic LASIK treatment
using the Amaris excimer laser were included. Eyes in which the LDV femtosecond
laser was used for flap creation were compared with eyes in which the Moria M2
microkeratome was used. RESULTS: The microkeratome group comprised 53 eyes and
the femtosecond laser group, 72 eyes. Baseline characteristics were similar
between groups (P > .05). The mean spherical equivalent (SE) deviation from
target 1 week postoperatively was -0.08 diopter (D) +/- 0.58 (SD) in the
femtosecond laser group and -0.06 +/- 0.87 D in the microkeratome group (P =
.92). Thereafter, the mean SE deviation from target increased gradually and by 6
months postoperatively was +0.30 +/- 0.50 D and +0.70 +/- 0.71 D, respectively (P
= .001). The correlation between the achieved and the attempted SE refraction was
better in the femtosecond laser group (R(2) = 0.806) than the microkeratome group
(R(2) = 0.671). CONCLUSIONS: Using the same nomogram, the short-term refractive
outcomes of hyperopic LASIK with flap creation performed with the femtosecond
laser were comparable to those for the microkeratome; however, the femtosecond
group showed significantly better stability over the 6-month follow-up and better
predictability, as reflected by a lower standard deviation and stronger Pearson
correlation. FINANCIAL DISCLOSURE: Dr. Arba Mosquera is an employee of Schwind
eye-tech-solutions GmbH and Co. KG. No other author has a financial or
proprietary interest in any material or method mentioned.
PMID- 26432117
TI - New posterior chamber phakic intraocular lens for high myopia: three-year
results.
AB - PURPOSE: To present the 3-year results regarding the safety and efficacy of the
Epi.Lens N, a new posterior chamber phakic intraocular lens (PC pIOL). SETTING:
Eye Center, University Hospital Freiburg, Freiburg, Germany. DESIGN: Prospective
clinical study. METHODS: A PC pIOL was implanted in highly myopic eyes of
consecutive patients. Standardized follow-up examinations including uncorrected
(UDVA) and corrected (CDVA) distance visual acuities and refractions were
performed 1, 3, and 6 months and 1, 2, and 3 years postoperatively. RESULTS: The
patient cohort consisted of 30 eyes of 16 patients. The study eyes had a mean
manifest refraction spherical equivalent of -10.1 diopters (D) +/- 3.4 (SD),
which decreased to -0.3 +/- 0.8 D postoperatively. After 3 years, all eyes
achieved (47%) or exceeded (53%) their preoperative CDVA, thus improving the mean
CDVA from 20/21 (0.94) preoperatively to 20/18 (1.14) postoperatively. The mean
postoperative UDVA (20/20 [0.98]) resembled the preoperative CDVA (20/21 [0.94]).
When analyzing all eyes with good visual potential (preoperative CDVA 20/20 or
better; n = 18), 94% achieved a postoperative UDVA of 20/20 or better. One small
diameter PC pIOL contacted the crystalline lens, which led to slight anterior
subcapsular lens opacification. Despite this, the patient achieved a CDVA of
20/20. CONCLUSION: The 3-year results of this pilot study of a new PC pIOL showed
good efficacy and safety. FINANCIAL DISCLOSURE: No author has a financial or
proprietary interest in any material or method mentioned.
PMID- 26432118
TI - Posterior chamber phakic intraocular lens sizing based on iris pigment layer
measurements by anterior segment optical coherence tomography.
AB - PURPOSE: To use anterior segment optical coherence tomography (AS-OCT) to
evaluate the clinical effectiveness of Implantable Collamer Lens posterior
chamber phakic intraocular lens (PC pIOL) sizing based on measurement of the
distance from the iris pigment end to the iris pigment end. SETTING: S. Fyodorov
Eye Microsurgery Federal State Institution, Moscow, Russia. DESIGN: Evaluation of
diagnostic test or technology. METHODS: Stage 1 was a prospective study. The
sulcus-to-sulcus (STS) distance was measured using ultrasound biomicroscopy (UBM)
(Vumax 2), and the distance from iris pigment end to iris pigment end was
assessed using a proposed AS-OCT algorithm. Part 2 used retrospective data from
patients after implantation of a PC pIOL with the size selected according to AS
OCT (Visante) measurements of the distance from iris pigment end to iris pigment
end. The PC pIOL vault was measured by AS-OCT, and adverse events were assessed.
RESULTS: Stage 1 comprised 32 eyes of 32 myopic patients (mean age 28.4 years +/-
6.3 [SD]; mean spherical equivalent [SE] -13.11 +/- 4.28 diopters [D]). Stage 2
comprised 29 eyes of 16 patients (mean age 27.7 +/- 4.7 years; mean SE -16.55 +/-
3.65 D). The mean STS distance (12.35 +/- 0.47 mm) was similar to the mean
distance from iris pigment end to iris pigment end distance (examiner 1: 12.36 +/
0.51 mm; examiner 2: 12.37 +/- 0.53 mm). The PC pIOL sized using the new AS-OCT
algorithm had a mean vault of 0.53 +/- 0.18 mm and did not produce adverse events
during the 12-month follow-up. In 16 of 29 eyes, the PC pIOL vault was within an
optimum interval (0.35 to 0.70 mm). CONCLUSION: The new measurement algorithm can
be effectively used for PC pIOL sizing. FINANCIAL DISCLOSURE: No author has a
financial or proprietary interest in any material or method mentioned.
PMID- 26432119
TI - Implantation of a diffractive trifocal intraocular lens: one-year follow-up.
AB - PURPOSE: To evaluate the visual, refractive, contrast-sensitivity, and
aberrometric outcomes during a 1-year follow-up after implantation of a trifocal
intraocular lens (IOL). SETTING: Premium Clinic, Teplice, Czech Republic. DESIGN:
Prospective case series. METHODS: This study included eyes of patients having
cataract surgery with implantation of the trifocal IOL model AT Lisa tri 839MP.
Distance, intermediate (66 and 80 cm), and near (33 and 40 cm) vision; contrast
sensitivity; aberrometric outcomes; and the defocus curve were evaluated during a
12-month follow-up. The level of posterior capsule opacification (PCO) was also
evaluated. RESULTS: In 120 eyes (60 patients), 1 month postoperatively, an
improvement was observed in all visual parameters (P <= .03) except corrected
near and intermediate visual acuities (both P >= .05). From 1 month to 12 months
postoperatively, small but statistically significant changes were observed in
uncorrected and corrected distance and near visual acuities (all P <= .03) and in
uncorrected intermediate visual acuity (P = .01). In the defocus curve, no
significant differences were found between visual acuities corresponding to
defocus levels of -1.0 diopter (D) and -2.0 D (P = .22). The level of ocular
spherical aberration decreased statistically significantly at 6 months (P <
.001). Ocular and internal higher-order aberrations increased minimally but
significantly from 6 to 12 months postoperatively (P < .001). The mean 12-month
PCO score was 0.32 +/- 0.44 (SD). Four eyes (3.3%) required neodymium:YAG
capsulotomy. CONCLUSION: The trifocal IOL provided complete and stable visual
restoration after cataract surgery during a 12-month follow-up, with good levels
of visual quality. FINANCIAL DISCLOSURE: No author has a financial or proprietary
interest in any material or method mentioned.
PMID- 26432120
TI - Comparison of a trifocal intraocular lens with a +3.0 D bifocal IOL: results of a
prospective randomized clinical trial.
AB - PURPOSE: To compare visual outcomes in patients with cataract surgery and
bilateral implantation of a trifocal or bifocal intraocular lens (IOL). SETTING:
University Eye Clinic Maastricht, the Netherlands. DESIGN: Prospective randomized
clinical trial. METHODS: Eyes with cataract and less than 1.0 diopter (D) of
corneal astigmatism were randomized to receive bilateral implantation of
Finevision Micro F trifocal IOLs or Acrysof IQ Restor +3.0 bifocal IOLs. Outcome
measures were monocular and binocular uncorrected distance (UDVA), uncorrected
intermediate (UIVA), and uncorrected near (UNVA) visual acuities; refractive
outcomes; binocular defocus curve; contrast sensitivity; reading speed; patient
satisfaction; and spectacle independence. RESULTS: Six months postoperatively,
the mean binocular UDVA, UIVA, and UNVA in 56 eyes of 28 patients were 0.01
logMAR +/- 0.11 (SD), 0.32 +/- 0.15 logMAR, and 0.15 +/- 0.13 logMAR in the
trifocal group (n = 15) and 0.00 +/- 0.09 logMAR, 0.28 +/- 0.08 logMAR, and 0.12
+/- 0.08 logMAR in the bifocal group (n = 13), respectively. The trifocal group
showed a more continuous defocus curve and better results at -1.0 D of defocus (P
< .01). The mean mesopic contrast sensitivity was higher in the bifocal group (P
= .02). Complete spectacle independence was reported by 80% of trifocal patients
and 50% of bifocal patients. There were no significant differences in refractive
outcomes, reading speed, or patient satisfaction. CONCLUSION: This study showed
noninferiority of visual outcomes with the trifocal IOL compared with the bifocal
IOL, although the defocus curve was better at an intermediate distance with the
trifocal IOL. FINANCIAL DISCLOSURE: Dr. Bauer received study grants from Alcon
Laboratories, Inc., Carl Zeiss Meditec AG, and Physiol S.A. and a lecture fee
from Alcon Surgical, Inc. Dr. Nuijts is a consultant to Alcon Surgical, Inc.,
Thea Pharma GmbH, and ASICO LLC; he has received study grants from Acufocus,
Inc., Alcon Surgical, Inc., Carl Zeiss Meditec AG, Ophtec BV, and Physiol S.A. No
other author has a financial or proprietary interest in any material or method
mentioned.
PMID- 26432121
TI - Correction of low levels of astigmatism.
AB - PURPOSE: To reevaluate the analysis of the correction of astigmatism. SETTING:
Academia, industry, and private practice. DESIGN: Evaluation of diagnostic test
or technology. METHODS: Astigmatic refractive surgery outcomes are based on
vector methods, including the correction index (also known as the correction
ratio), which is the ratio of the surgically induced astigmatism to the target
induced astigmatism (TIA). Mean correction indices substantially greater than 1
have been reported for astigmatic corrections less than 1.00 diopter (D) and as
representing systematic overcorrection. We hypothesize that this reflects a
limitation of the correction index rather than systematic flaws in treatments.
The theoretical mathematic behavior of the correction index was analyzed,
accounting for variability in astigmatism measurement. Then, the impact of
cylinder measurement variability on the mean correction index was modeled. A
Monte Carlo simulation was performed and calculated 10 000 values of correction
index for various values of TIA. Finally, correction indices from published and
unpublished studies of refractive lasers were compared with the simulations.
RESULTS: The mean correction index is always greater than 1 for the case of a
perfect refractive correction; however, for astigmatic corrections less than 1.00
D, the mean correction index increases sharply because the measurement
variability is similar in magnitude to TIA. Almost all previous studies show the
predicted increase in the correction index for low astigmatic corrections.
CONCLUSION: The correction index is a useful vector-based metric for the
evaluation of refractive procedures, but mean values greater than 1 should be
anticipated for lower astigmatic treatments and do not necessarily represent
systematic overcorrection. FINANCIAL DISCLOSURE: Dr. Bullimore is a consultant to
Alcon Surgical, Inc., Carl Zeiss Meditec AG, Digital Vision Systems, Essilor,
Innovega, Inc., and Paragon Vision Sciences, Inc. Dr. Spooner is a consultant to
Alcon Surgical, Inc., Carl Zeiss Meditec AG, Digital Vision Systems, Thru-Focus
Optics LLC, and i2eyediagnostics, Ltd. Dr. Dishler is a consultant to Carl Zeiss
Meditec AG and Revision Optics, Inc. Dr. Sluyterman is an employee of Carl Zeiss
Meditec AG.
PMID- 26432122
TI - Comparison of SRK/T and Haigis formulas for predicting corneal astigmatism
correction with toric intraocular lenses.
AB - PURPOSE: To compare the accuracy of the SRK/T and Haigis formulas for predicting
corneal astigmatism correction with a toric intraocular lens (IOL). SETTING:
Department of Ophthalmology, Korea University College of Medicine, Seoul, South
Korea. DESIGN: Retrospective cross-sectional study. METHODS: Eyes with an Acrysof
toric IOL were enrolled in the study. The corneal plane effective cylinder power
of toric IOLs (target induced astigmatism vector [TIA]) predicted by the SRK/T
and Haigis formulas were compared with the cylindrical correction achieved
postoperatively (surgically induced astigmatism vector [SIA]). The magnitude of
error was defined as the difference between the magnitudes of the SIA and TIA.
The median absolute magnitudes of error predicted by the SRK/T and Haigis
formulas were compared. The median absolute errors predicted by the 2 formulas
were also compared. RESULTS: The mean postoperative SIA was 1.80 diopters (D) +/-
0.55 (SD). The magnitude of error predicted by the SRK/T and Haigis formulas was
0.31 +/- 0.40 D and 0.23 +/- 0.40 D, respectively. The median absolute magnitude
of error predicted by the Haigis formula was statistically significantly smaller
than that predicted by the SRK/T formula (P < .001). The median absolute error
predicted by the Haigis formula (0.35 D) was also statistically significantly
smaller than that predicted by the SRK/T formula (0.43 D) (P = .003). CONCLUSION:
The Haigis formula was more accurate than the SRK/T formula not only in
predicting the refractive outcome but also in predicting corneal astigmatism
correction by toric IOLs. FINANCIAL DISCLOSURE: No author has a financial or
proprietary interest in any material or method mentioned.
PMID- 26432123
TI - Comparison of corneal power, astigmatism, and wavefront aberration measurements
obtained by a point-source color light-emitting diode-based topographer, a
Placido-disk topographer, and a combined Placido and dual Scheimpflug device.
AB - PURPOSE: To evaluate and compare the performance of a point-source color light
emitting diode (LED)-based topographer (color-LED) in measuring anterior corneal
power and aberrations with that of a Placido-disk topographer and a combined
Placido and dual Scheimpflug device. SETTING: Cullen Eye Institute, Baylor
College of Medicine, Houston, Texas USA. DESIGN: Retrospective observational case
series. METHODS: Normal eyes and post-refractive-surgery eyes were consecutively
measured using color-LED, Placido, and dual-Scheimpflug devices. The main outcome
measures were anterior corneal power, astigmatism, and higher-order aberrations
(HOAs) (6.0 mm pupil), which were compared using the t test. RESULTS: There were
no statistically significant differences in corneal power measurements in normal
and post-refractive surgery eyes and in astigmatism magnitude in post-refractive
surgery eyes between the color-LED device and Placido or dual Scheimpflug devices
(all P > .05). In normal eyes, there were no statistically significant
differences in 3rd-order coma and 4th-order spherical aberration between the
color-LED and Placido devices and in HOA root mean square, 3rd-order coma, 3rd
order trefoil, 4th-order spherical aberration, and 4th-order secondary
astigmatism between the color-LED and dual Scheimpflug devices (all P > .05). In
post-refractive surgery eyes, the color-LED device agreed with the Placido and
dual-Scheimpflug devices regarding 3rd-order coma and 4th-order spherical
aberration (all P > .05). CONCLUSIONS: In normal and post-refractive surgery
eyes, all 3 devices were comparable with respect to corneal power. The agreement
in corneal aberrations varied. FINANCIAL DISCLOSURE: Drs. Wang, Koch, and Weikert
are consultants to Ziemer Ophthalmic Systems AG. Dr. Koch is a consultant to
Abbott Medical Optics, Inc., Alcon Surgical, Inc., and i-Optics Corp.
PMID- 26432124
TI - Effect of tear osmolarity on repeatability of keratometry for cataract surgery
planning.
AB - PURPOSE: To evaluate the effects of tear osmolarity on the repeatability of
keratometry (K) measurements in patients presenting for cataract surgery.
SETTING: Three clinical practices. DESIGN: Observational prospective
nonrandomized study. METHODS: Subjects were prospectively recruited based on tear
osmolarity (Tearlab Osmolarity System); that is, osmolarity more than 316 mOsm/L
in at least 1 eye (hyperosmolar) and osmolarity less than 308 mOsm/L in both eyes
(normal). The baseline K value was measured, and a second measurement was taken
on the same instrument (IOLMaster) within 3 weeks of the first. Variability in
average K, calculated corneal astigmatism using vector analysis, and intraocular
lens (IOL) sphere power calculations were compared between groups. RESULTS: The
hyperosmolar group (50 subjects) had a statistically significantly higher
variability in the average K reading (P = .05) than the normal group (25
subjects) and a statistically significantly higher percentage of eyes with a 1.0
diopter (D) or greater difference in the measured corneal astigmatism (P = .02).
A statistically significantly higher percentage of eyes in the hyperosmolar group
had an IOL power difference of more than 0.5 D (P = .02). No statistically
significant differences were present when the subjects were grouped by self
reported dry eye. CONCLUSIONS: Significantly more variability in average K and
anterior corneal astigmatism was observed in the hyperosmolar group, with
significant resultant differences in IOL power calculations. Variability was not
significantly different when subjects were grouped by self-reported dry eye.
Measurement of tear osmolarity at the time of cataract surgery planning can
effectively identify patients with a higher likelihood of high unexpected
refractive error resulting from inaccurate keratometry. FINANCIAL DISCLOSURE:
Drs. Epitropoulos, Matossian, Berdy, and Malhotra received compensation from
Tearlab for participating in the study. No author has a financial or proprietary
interest in any material or method mentioned.
PMID- 26432125
TI - Comparability of anterior chamber depth measurements with partial coherence
interferometry and optical low-coherence reflectometry in pseudophakic eyes.
AB - PURPOSE: To assess whether anterior chamber depth (ACD) measurements in
pseudophakic eyes obtained with partial coherence interferometry (PCI) and
optical low-coherence reflectometry (OLCR) devices can be used interchangeably.
SETTING: Vienna Institute for Research in Ocular Surgery, A Karl Landsteiner
Institute, Hanusch Hospital, Vienna, Austria. DESIGN: Prospective case series.
METHODS: The ACD measurements in 1 eye of each pseudophakic patient were
performed with the PCI-based ACMaster device and the OLCR-based Lenstar LS900
device at least 1 day postoperatively. RESULTS: The study comprised 65 eyes of 65
patients with a mean age of 71.7 years +/- 9.0 (SD) (range 39 to 91 years). In 15
eyes, no valid ACD readings could be obtained with the OLCR device. No obvious
reason for these measurement failures was identified; however, tear-film
alterations shortly after surgery were suspected. No significant difference in
the mean ACD in the remaining 50 eyes was found between PCI measurements (5019 +/
660 MUm; range 4008 to 6181 MUm) and OLCR measurements (5015 +/- 663 MUm; range
4017 to 6163 MUm) (P = .06). Three (6%) of 50 measurements were not within the
95% limits of agreement in the Bland-Altman analysis. CONCLUSIONS: Pseudophakic
ACD measurements with the PCI and OLCR devices can be used interchangeably. The
OLCR device proved to be more user-friendly and faster; however, in a substantial
number of eyes, no usable values were obtainable. FINANCIAL DISCLOSURE: No author
has a financial or proprietary interest in any material or method mentioned.
PMID- 26432126
TI - Pediatric bag-in-the-lens intraocular lens implantation: long-term follow-up.
AB - PURPOSE: To evaluate long-term follow-up results of pediatric cataract surgery
using the bag-in-the-lens (BIL) intraocular lens (IOL) implantation technique.
SETTING: Antwerp University Hospital, Edegem, Antwerp, Belgium. DESIGN:
Prospective case series. METHODS: All pediatric cataract surgeries with BIL IOL
implantation performed at the Antwerp University Hospital were evaluated. Only
cases that completed a follow-up of 5 years at the hospital's Department of
Ophthalmology were included in this study. RESULTS: Forty-six eyes of 31 children
had a complete follow-up of 5 years or more after BIL IOL implantation. Sixteen
cases were unilateral and 15 were bilateral. Patient age at time of surgery
ranged from 2 months to 14 years. The mean refraction at the end of follow-up was
-1.99 diopters (D) +/- 3.70 (SD). In bilateral cases, a corrected distance visual
acuity (CDVA) of better than 0.5 was attained in 86.7% and a CDVA of 1.0 was
achieved in 56.7%. In unilateral cases, 31.2% achieved a CDVA of better than 0.5
but none obtained a CDVA of 1.0. A clear visual axis was maintained in 91.3% of
cases during follow-up. Visual axis reopacification was detected in 4 eyes of 3
cases, all due to inadequate BIL IOL positioning. None of these eyes needed more
than 1 intervention to maintain visual axis clarity. Other than 1 case of
glaucoma, no severe complications were detected. CONCLUSION: Long-term follow-up
results show that BIL IOL implantation is a safe, well-tolerated approach for
treating pediatric cataract with a very low rate of visual axis reopacification
and a low rate of secondary interventions for other postoperative complications.
FINANCIAL DISCLOSURE: Dr. Tassignon has intellectual property rights to the bag
in-the-lens intraocular lens (U.S. patent 6 027 531; EU patent
009406794.PCT/120268), which is licensed to Morcher GmbH, Stuttgart, Germany. No
other author has a financial or proprietary interest in any material or method
mentioned.
PMID- 26432127
TI - Traumatic cataracts secondary to combat ocular trauma.
AB - PURPOSE: To describe the characteristics, visual outcomes, and predictive value
of the Ocular Trauma Score (OTS) in eyes with traumatic cataract from combat
ocular trauma. SETTING: Walter Reed Army Medical Center, Washington, DC, USA.
DESIGN: Retrospective case series. METHODS: Records of service members with
traumatic cataract from combat ocular trauma over a 7-year period were reviewed.
Visual acuity at initial presentation and visual acuity at the final follow-up
were compared in addition to outcomes in closed versus open globes, by final lens
status, and in eyes receiving primary versus secondary intraocular lenses (IOLs).
Visual outcomes were predicted using the OTS and compared to the achieved
corrected distance visual acuity (CDVA). RESULTS: A total of 181 eyes of 167
patients were included in the final analysis. Twenty-six percent of all eye
injuries sustained traumatic cataract. The mean final visual outcome was 0.86
logMAR +/- 1.01 (SD) with 44 no light perception (NLP) eyes and 26 light
perception (LP) eyes compared with an initial visual acuity of 2.41 +/- 0.88
logMAR with 27 no NLP eyes and 64 LP eyes (P <= .001, 2-tailed Student t test).
Final CDVAs in eyes receiving primary IOLs were 0.72 +/- 0.84 logMAR with 1 NLP
and 1 LP eye versus 0.51 +/- 0.78 logMAR with 2 LP eyes in eyes receiving a
secondary IOL (P = .37, Student t test). CONCLUSION: Traumatic cataracts are
frequently associated with ocular trauma. The OTS is a reliable means of
predicting visual outcome. There was no difference in eyes receiving primary IOLs
versus secondary IOLs. FINANCIAL DISCLOSURE: No author has a financial or
proprietary interest in any material or method mentioned.
PMID- 26432128
TI - Effect of a hyaluronic acid and carboxymethylcellulose ophthalmic solution on
ocular comfort and tear-film instability after cataract surgery.
AB - PURPOSE: To evaluate the efficacy and safety of using sodium hyaluronate 0.1% and
carboxymethylcellulose 0.5% artificial tears for ocular discomfort and tear-film
stability in eyes after cataract surgery. SETTING: Twenty ophthalmic centers in
Italy. DESIGN: Prospective randomized case series. METHODS: This study enrolled
patients scheduled for unilateral cataract surgery. After surgery, patients
received artificial tears and a topical steroid-antibiotic (study group) or
topical steroid-antibiotic alone (control group) and were assessed
postoperatively at 1 and 5 weeks. Outcome measures were tear breakup time (TBUT),
ocular surface disease index (OSDI), frequency of dry-eye symptoms evaluated
using a visual analog scale (VAS), and corneal fluorescein staining. RESULTS: The
study comprised 282 patients. At 5 weeks, the mean TBUT was statistically
significantly higher in the study group than in the control group (P = .0003).
The mean OSDI score statistically significantly improved in both groups from 1 to
5 weeks (P < .0001 for both groups); however, there was no statistically
significant difference between the groups at these timepoints. The artificial
tears statistically significantly improved VAS-assessed dry-eye symptoms in the
study group compared with the control group at 5 weeks (P < .001). The mean
corneal fluorescein staining was significantly reduced in the study group
compared with the control group at 5 weeks (P = .002 versus P = .05,
respectively). No treatment-related adverse events were reported. CONCLUSION:
Sodium hyaluronate 0.1% and carboxymethylcellulose 0.5% ophthalmic solution was
effective and well tolerated in reducing dry-eye disease symptoms and improving
the clinical outcome after cataract surgery. FINANCIAL DISCLOSURE: No author has
a financial or proprietary interest in any material or method mentioned.
PMID- 26432129
TI - Association between serum 25-hydroxyvitamin D levels and age-related cataracts.
AB - PURPOSE: To investigate associations between serum 25-hydroxyvitamin D levels and
age-related cataracts. SETTING: Department of Ophthalmology, College of Medicine,
Catholic University of Korea, South Korea. DESIGN: Observational cross-sectional
study. METHODS: Participants aged 40 years or older in the fourth (2008 to 2009)
and fifth (2010 to 2012) Korea National Health and Nutrition Examination Survey
(KNHANES) had evaluation of their serum 25-hydroxyvitamin D levels and ophthalmic
slitlamp examinations to identify cataract. An age-related cataract was defined
as the presence of a cortical, nuclear, anterior subcapsular, posterior
subcapsular, or mixed cataract or a history of cataract surgery. RESULTS: The
study evaluated eyes of 18 804 patients. The mean levels of serum 25
hydroxyvitamin D were 20.0 ng/mL in men and 17.5 ng/mL in women. In men, but not
in women, the odds ratio (OR) for age-related cataracts decreased statistically
significantly when the serum 25-hydroxyvitamin D levels were in the highest
quintile than when they were in the lowest quintile (OR, 0.76; 95% confidence
interval, 0.59-0.99) after adjusting for potentially confounding factors
including age, sex, smoking status, diabetes, hypertension, and sunlight
exposure. However, trend analysis did not show a significant declining trend in
the cataract risk associated with higher serum 25-hydroxyvitamin D quintiles (P =
.084). In women, serum 25-hydroxyvitamin D levels were not associated with age
related cataracts. CONCLUSIONS: The age-related cataract risk decreased in men
with higher serum 25-hydroxyvitamin D levels than in those with lower serum 25
hydroxyvitamin D levels after adjusting for potential confounding factors. In
light of previous research indicating an antioxidative effect of vitamin D, the
connection between vitamin D and age-related cataract warrants further study.
FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in
any material or method mentioned.
PMID- 26432130
TI - Efficacy and safety of combined cataract surgery with 2 trabecular microbypass
stents versus ab interno trabeculotomy.
AB - PURPOSE: To compare the outcomes of combined cataract surgery with trabecular
microbypass stents and ab interno trabeculotomy in patients with open-angle
glaucoma. SETTING: University of Toronto, Toronto, Ontario, and University of
Montreal, Montreal, Quebec, Canada, and Glaucoma Associates of Texas, Dallas,
Texas, USA. DESIGN: Retrospective case series. METHODS: Patients with primary
open-angle, pseudoexfoliative, or pigmentary dispersion glaucoma were included.
Primary outcome measures were intraocular pressure (IOP), postoperative
medications, success (IOP <=18 mm Hg, no glaucoma medications or reoperations),
and postoperative adverse events. RESULTS: The average patient age was 76.5 years
+/- 12 [SD]. Forty-nine eyes had phacoemulsification and 2 had stent
implantations; 52 eyes had phacoemulsification and trabeculotomy surgery with a
12-month postoperative follow-up. The analysis of variance indicated a
significant reduction in mean IOP from baseline to 12 months for stent (19.6 +/-
5.3 mm Hg to 14.3 +/- 3.1 mm Hg; P < .001) and trabeculotomy (20.6 +/- 6.8 mm Hg
to 17.3 +/- 6.5 mm Hg; P < .001) and lower mean IOP at 12 months in the stent
group (P = .01). The median number of glaucoma medications decreased from
baseline to 12 months in both groups and was lower in the stent group at 3, 6,
and 12 months. Thirty-nine percent (19 eyes) in the stent group and 14% (7 eyes)
in the trabeculotomy group achieved success at 12 months (P = .006). The
incidence of hyphema was lower in the stent group (P = .008). CONCLUSIONS: Both
types of surgery achieved a significant reduction in IOP and medication use at 12
months, with the stent group achieving higher success and a reduced incidence of
postoperative hyphema. FINANCIAL DISCLOSURE: Dr. Ahmed is a consultant to and
investigator for Glaukos Corp., Ivantis, Inc., Transcend Medical, Inc., and
Aquesys, Inc., and has received speaker honoraria from Neomedix, Inc. Dr. Saheb
has received travel funding from Glaukos Corp., Ivantis, Inc., and Transcend
Medical, Inc., and a research grant from Ivantis, Inc. Dr. Harasymowycz has
received a research grant from Ivantis, Inc. Dr. Fellman is a consultant to Endo
Optiks, Inc., and has received honoraria from Optous and research funds from
Ivantis, Inc., Glaukos Corp., and Transcend Medical, Inc. No other author has a
financial or proprietary interest in any material or method mentioned.
PMID- 26432131
TI - Changes in intraocular pressure after cataract surgery: analysis of the Swedish
National Cataract Register Data.
AB - PURPOSE: To analyze changes in intraocular pressure (IOP) after cataract surgery
based on data from the Swedish National Cataract Register (NCR). SETTING:
Ophthalmic surgery units in Sweden. DESIGN: Prospective database study. METHODS:
Data for 2012 through 2014 were obtained prospectively from the NCR. The outcome
register of the NCR has collected data on IOP before and a mean of 37.7 days +/-
29.1 (SD) after cataract surgery since 2012. RESULTS: The analyses were based on
20 437 cataract extractions reported during 1 month each year to the outcome
registry of the NCR. Cataract surgery was found to reduce IOP by a mean of 1.46
mm Hg, which was statistically significant (P < .001). A larger IOP reduction was
seen in cases with a higher preoperative IOP (r = 0.557, P < .001). Older
patients and shorter eyes had a greater IOP reduction after surgery (P < .001 and
P = .001, respectively). Women had a greater IOP reduction than men (P = .04)
When high IOP was given as an indication for surgery, the IOP reduction after
cataract surgery was 5.50 mm Hg compared with a reduction of 1.40 mm Hg in
patients for whom this indication was not given (P < .001). Patients with
glaucoma or pseudoexfoliation (PXF) had a more pronounced IOP reduction than
patients without these diagnoses (P < .001). CONCLUSION: Cataract surgery had an
IOP-lowering effect, in particular in older patients, women, short eyes, eyes
with high preoperative IOP, and eyes with glaucoma or PXF. FINANCIAL DISCLOSURE:
No author has a financial or proprietary interest in any material or method
mentioned.
PMID- 26432132
TI - Mechanical epithelial removal followed by corneal collagen crosslinking in
progressive keratoconus: short-term complications.
AB - PURPOSE: To compare the complications occurring within the first 3 months of
corneal collagen crosslinking (CXL) performed with mechanical or transepithelial
phototherapeutic keratectomy (PTK) epithelial removal in keratoconus patients.
SETTING: Yildirim Beyazit University Ataturk Training and Research Hospital,
Ankara, Turkey. DESIGN: Nonrandomized retrospective clinical study. METHODS: Eyes
of consecutive progressive keratoconus patients who had PTK or mechanical
epithelial removal followed by CXL were included. All patients were examined
regularly until epithelial healing. Detailed ophthalmologic examinations were
performed preoperatively and 1 and 3 months postoperatively. RESULTS: The study
comprised 499 eyes (302 patients) that had transepithelial PTK (Group 1, 153
eyes) or mechanical epithelial removal (Group 2, 256 eyes) followed by CXL.
Delayed epithelial healing occurred in 15.0% of eyes in Group 1 and 3.5% of eyes
in Group 2 (P = .001). Epithelial hypertrophy occurred in 24.8% of eyes and 3.5%
of eyes, respectively (P = .001). Salzmann-like epithelial nodules (2.6%),
epithelial herpetic keratitis (1.9%), anterior uveitis (1.9%), and elevated
intraocular pressure (1.9%) occurred in Group 1 only and infective keratitis
(0.8%) in Group 2 only. Marked stromal edema and peripheral sterile infiltrates
occurred at similar rates in both groups (P = .567 and P = .479, respectively).
Grade 1+ corneal haze was significantly high in Group 2. Grade 2+ and 3+ haze was
significantly high in Group 1 (P = .001). CONCLUSIONS: Ocular surface healing
disorders were the most common early complications of CXL. Short-term
complications were higher with the transepithelial PTK epithelial removal
technique than with mechanical epithelial removal. FINANCIAL DISCLOSURE: No
author has a financial or proprietary interest in any material or method
mentioned.
PMID- 26432133
TI - Evaluation of stability and capsular bag opacification with a foldable
intraocular lens coupled with a protective membrane in the rabbit model.
AB - PURPOSE: To evaluate the stability and capsular bag opacification of a smooth or
a patterned silicone protective membrane implanted in the bag with secondary
placement of an intraocular lens (IOL). SETTING: John A. Moran Eye Center,
University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study.
METHODS: Twelve New Zealand rabbits had bilateral implantation of a protective
membrane and an IOL or an IOL alone. Three groups of 8 eyes each received the IOL
and the smooth protective membrane, the IOL and the patterned membrane, or the
IOL alone. Slitlamp examination was performed weekly for 4 weeks. The rabbits
were then humanely killed and their globes enucleated. Capsular bag opacification
was scored based on the Miyake-Apple view, and the eyes underwent histopathology.
RESULTS: At 4 weeks, the mean central posterior capsule opacification (PCO) score
was 0.28 +/- 0.32 (SD) in all eyes with a protective membrane and 2.08 +/- 1.28
in eyes with the IOL alone (P < .00001, Student t test). Peripheral PCO and
Soemmerring ring formation were also significantly less in eyes with the
protective membrane. Histopathologically, the posterior capsules were relatively
clear in most IOLs with the protective membrane. The smooth and patterned
protective membranes showed a significant difference in overall capsular bag
opacification formation compared with the IOLs without the membrane. CONCLUSIONS:
The circular geometry of the protective membrane led to expansion of the capsular
bag and appeared to prevent capsular bag opacification. Further studies are
warranted to assess whether the pattern on the device's posterior surface further
enhances this effect. FINANCIAL DISCLOSURE: No author has a financial or
proprietary interest in any material or method mentioned.
PMID- 26432134
TI - Resistance force for intraocular lens insertion through lens cartridges and
syringe-type injectors.
AB - PURPOSE: To measure and compare the resistance force for intraocular lens (IOL)
insertion using 5 syringe-type injector systems. SETTING: Tokyo Medical
University and laboratory in Kowa Co., Tokyo, Japan. DESIGN: Experimental study.
METHODS: Intraocular lenses were inserted into the lens capsular bag of porcine
eyes after phacoemulsification using 5 implantation systems (Groups A, B, C, D,
and E). For each system, the resistance force for IOL insertion to the lens
capsular bag of porcine eyes was measured using an automated force gauge system.
For control, the resistance force for IOL delivery into a plastic dish was
measured. Changes in the resistance force and its curve and maximum value were
evaluated. The mean total area under the curve (AUC) was compared. Data were
statistically analyzed. RESULTS: For all groups, the mean resistance forces were
17.2, 6.3, 4.2, 20.7, and 2.3 newtons (N), respectively, in porcine eyes, and
14.4, 5.8, 4.5, 12.6, and 2.2 N in controls. The mean sizes of the total AUC were
43 371, 8465, 6771, 30 306, and 2334 pixels in porcine eyes and 40 940, 7080,
6876, 20 710, and 2215 pixels in controls; the correlation coefficients between
the resistance forces and the sizes of the total area were 0.576, 0.113, 0.346,
0.726, and 0.933 in porcine eyes and 0.707, 0.557, 0.914, 0.951, and 0.893 in
controls. CONCLUSION: Resistance force and its curve were clarified in 5 IOL
implantation systems. Appropriate IOL and injector selection may be achieved
after clarifying resistance force and its waveform during IOL insertion.
FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in
any material or method mentioned.
PMID- 26432135
TI - Effects of torsional movements in refractive procedures.
AB - Using PubMed and our internal database, we extensively reviewed the literature on
the history of measurement of torsional movements of the eye from 1963 to the
present, focusing specifically on the implications of torsional measurement and
compensation in corneal refractive and ocular surgery. Mean cyclotorsional
movements observed in refractive surgery procedures have been reported to be
around 3 degrees, which can be well controlled by the currently used technology.
Torsional movements affect aberrations with a vectorial component (astigmatic
procedures) more adversely. Currently available eye-registration technology
provides an accuracy of +/-1.5 degrees. The vectorial components of residual
aberrations can be minimized by intentionally underplanning the refractive
treatments. The gaps in our knowledge limit the precision in current surgical
procedures due to imperfect cyclotorsion compensation. This review summarizes
about the explored aspects of torsional movements in surgical applications and
raises questions about the unexplored implications. FINANCIAL DISCLOSURE: Dr.
Arba Mosquera and Mr. Verma are employees of Schwind eye-tech-solutions GmbH and
Co. KG.
PMID- 26432136
TI - Femtosecond laser-assisted primary posterior capsulotomy for toric intraocular
lens fixation and stabilization.
AB - We describe 2 cases in which a spontaneously rotated toric intraocular lens (IOL)
was fixated and stabilized using the femtosecond laser to create a primary
posterior capsulotomy for posterior optic capture. We also review the literature
on previous techniques that have been used to prevent or stabilize recurrent
toric IOL rotation. The design of toric IOLs must be evaluated further to
determine the risk for rotation in myopic eyes. FINANCIAL DISCLOSURE: Dr. Scott
is a consultant to Abbott Medical Optics, Inc. Neither author has a financial or
proprietary interest in any material or method mentioned.
PMID- 26432137
TI - Early-onset methicillin-resistant Staphylococcus aureus keratitis and late-onset
infectious keratitis in astigmatic keratotomy incision following femtosecond
laser-assisted cataract surgery.
AB - A 79-year-old woman had uneventful femtosecond laser-assisted cataract surgery
including paired laser astigmatic keratotomies (AKs) in the right eye. Three
weeks postoperatively, a corneal infiltrate developed in the superotemporal AK
incision. Cultures grew methicillin-resistant Staphylococcus aureus. The
infection was treated with topical fortified vancomycin and tobramycin; full
resolution required several months of therapy. Five months after cataract
surgery, the patient presented with a second stromal infiltrate, also in the
superotemporal AK incision. Despite negative cultures, the infiltrate resolved
quickly on a short course of broad-spectrum fortified antibiotics. At 6 months,
the corrected distance visual acuity was 20/30. This case demonstrates that
infectious keratitis can occur following uneventful femtosecond laser-assisted AK
performed concurrently with cataract surgery. We reviewed the literature on
infectious keratitis following refractive keratotomy and femtosecond laser
assisted procedures. Several recommendations to prevent these infections are
proposed. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest
in any material or method mentioned.
PMID- 26432138
TI - Massilia timonae as cause of chronic endophthalmitis following cataract surgery.
AB - This is the first report of chronic postoperative endophthalmitis caused by
Massilia timonae. The gram-negative bacillus was isolated from a patient who
developed chronic endophthalmitis after cataract extraction. The microorganism
was cultured on brain-heart infusion broth and identified using the 16S rRNA
sequence analysis. Biochemically, the organism was positive for catalase and
oxidase and negative for arginine dihydrolase. It was pansensitive to beta
lactams, fluoroquinolones, aminoglycosides, and trimethoprim-sulfamethoxazole but
resistant to aztreonam. Massilia timonae is a new bacterium implicated in
postoperative chronic endophthalmitis. Eubacterial polymerase chain reaction was
useful in identifying M timonae because phenotyping testing and conventional
algorithms could not identify it. FINANCIAL DISCLOSURE: No author has a financial
or proprietary interest in any material or method mentioned.
PMID- 26432139
TI - Bibliometric analysis of literature on cataract research in PubMed (2001-2013).
PMID- 26432140
TI - Association between age and incidence of posterior capsule rupture during
cataract surgery: cross-sectional study.
PMID- 26432141
TI - Structural changes of the anterior chamber following cataract surgery during
infancy.
PMID- 26432142
TI - Peaked Pupil One Day After Cataract Surgery: August consultation #1.
PMID- 26432143
TI - August consultation #2.
PMID- 26432144
TI - August consultation #3.
PMID- 26432145
TI - August consultation #4.
PMID- 26432146
TI - August consultation #5.
PMID- 26432147
TI - August consultation #6.
PMID- 26432148
TI - August consultation #7.
PMID- 26432149
TI - August consultation #8.
PMID- 26432150
TI - Potential confounding factors in a comparison of femtosecond laser-assisted
cataract surgery versus standard phacoemulsification.
PMID- 26432151
TI - Reply: To PMID 25466483.
PMID- 26432152
TI - Other comparators for outcomes in treatment of astigmatism with toric intraocular
lenses.
PMID- 26432153
TI - Pain during phacoemulsification with and without cryoanalgesia.
PMID- 26432154
TI - Reply: To PMID 25936681.
PMID- 26432155
TI - Reply: To PMID 25840296.
PMID- 26432156
TI - Influence of corneal asphericity on refractive outcomes after cataract surgery.
PMID- 26432157
TI - Reply: To PMID 25840302.
PMID- 26432158
TI - Generation of iPSC line MU011.A-hiPS from homozygous alpha-thalassemia fetal skin
fibroblasts.
AB - Human iPSC line MU011.A-hiPS was generated from homozygous alpha-thalassemia (
(SEA)/-(SEA)) fetal skin fibroblasts using a non-integrative reprogramming
method. Reprogramming factors OCT3/4, SOX2, KLF4, L-MYC, LIN28, and shRNA of TP53
contained in three episomal vectors were delivered using electroporation.
PMID- 26432159
TI - Roles of oxidative stress and the ERK1/2, PTEN and p70S6K signaling pathways in
arsenite-induced autophagy.
AB - Studies show that arsenite induces oxidative stress and modifies cellular
function via phosphorylation of proteins and inhibition of DNA repair enzymes.
Autophagy, which has multiple physiological and pathological roles in cellular
function, is initiated by oxidative stress and is regulated by the signaling
pathways of phosphatidylinositol 3-phosphate kinase (PI3K)/mammalian target of
rapamycin (mTOR)/p70S6 kinase (p70S6K) and extracellular signaling-regulated
protein kinase 1/2 (ERK1/2) that play important roles in oncogenesis. However,
the effects of arsenite-induced oxidative stress on autophagy and on expression
of related proteins are not fully understood. This study found that cells treated
with sodium arsenite had reduced 8-oxoguanine DNA glycosylase 1 (OGG1) and
increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) and activating transcription
factor (ATF) 3 in SV-40 immortalized human uroepithelial (SV-HUC-1) cells.
Arsenite also increased the number of autophagosomes and increased levels of the
autophagy markers Beclin-1 and microtubule-associated protein 1 light chain 3B.
Reactive oxygen species scavenger decreased arsenite-induced autophagy in SV-HUC
1 cells. Our previous work showed that arsenite induced phosphorylation of the
ERK1/2 signaling pathway. The current study further showed that arsenite
decreased phosphatase and tensin homologue (PTEN) levels and increased phospho
p70S6 kinase (p-p70S6K) in SV-HUC-1 cells. However, both kinase inhibitor U0126
and the DNA (cytosine-5-)-methyltransferase 1 (DNMT1) inhibitor 5-aza
deoxycytidine abolished the effect of arsenite on expressions of PTEN and p
p70S6K. These results show that autophagy induced by arsenite exposure is
mediated by oxidative stress, which regulates activation of the PTEN, p70S6K and
ERK1/2 signaling pathways. Thus, this study clarifies the role of autophagy in
arsenite-induced urothelial carcinogenesis.
PMID- 26432160
TI - Expression and functionality of transient receptor potential melastatin 4 (TRPM4)
like channels during development of the zebrafish.
AB - Calcium signaling, from localized spikes to coordinated waves, are linked to
cleavage, patterning, differentiation, and growth during embryonic development.
The basis for control of these Ca(2+) signals is poorly defined. In this study,
the expression and functionality of the transient receptor potential melastatin 4
protein (TRPM4), an ion channel that controls Ca(2+) entry into cells, was
examined in the zebrafish embryo and adult. Originating with the human TRPM4
gene, Ensembl ortholog, NCBI BLAST, and Homologene searches identified a
zebrafish TRPM4 "like" gene encoding a predicted protein of 1199 amino acids and
sharing a 42-43% sequence identity with the mouse, rat, and human. Custom
designed zebrafish primers identified TRPM4 transcripts throughout the 0-123h
period of embryonic development with greatest and lowest relative expression at
12 and 123h post-fertilization, respectively. Perforated patch clamp recordings
in 27h embryonic cells revealed Ca(2+)-activated currents with the
characteristics of those described for mammalian TRPM4. Similarly, TRPM4-like
expression and functionality was observed in brain and liver cells from adult
fish. These findings suggest that a TRPM4-like channel is available for Ca(2+)
regulation during early development of the zebrafish.
PMID- 26432161
TI - Gemfibrozil disrupts the metabolism of circulating lipids in bobwhite quails.
AB - The circulating lipids of birds play essential roles for egg production and as an
energy source for flight and thermogenesis. How lipid-lowering pharmaceuticals
geared to prevent heart disease in humans and that are routinely released in the
environment affect their metabolism is unknown. This study assesses the impact of
the popular drug gemfibrozil (GEM) on the plasma phospholipids (PL), neutral
lipids (NL), and nonesterified fatty acids (NEFA) of bobwhite quails (Colinus
virginianus). Results show that bird lipoproteins are rapidly altered by GEM,
even at environmentally-relevant doses. After 4 days of exposure, pharmacological
amounts cause an 83% increase in circulating PL levels, a major decrease in
average lipoprotein size measured as a 56% drop in the NL/PL ratio, and important
changes in the fatty acid composition of PL and NEFA (increases in fatty acid
unsaturation). The levels of PL carrying all individual fatty acids except
arachidonate are strongly stimulated. The large decrease in bird lipoprotein size
may reflect the effects seen in humans: lowering of LDL that can cause
atherosclerosis and stimulation of HDL that promote cholesterol disposal. Lower
(environmental) doses of GEM cause a reduction of %palmitate in all the plasma
lipid fractions of quails, but particularly in the core triacylglycerol of
lipoproteins (NL). No changes in mRNA levels of bird peroxisome proliferator
activated receptor (PPAR) could be demonstrated. The disrupting effects of GEM on
circulating lipids reported here suggest that the pervasive presence of this drug
in the environment could jeopardize reproduction and migratory behaviours in wild
birds.
PMID- 26432162
TI - Comparison of the occurrence and survival of fecal indicator bacteria in
recreational sand between urban beach, playground and sandbox settings in
Toronto, Ontario.
AB - While beach sands are increasingly being studied as a reservoir of fecal
indicator bacteria (FIB), less is known about the occurrence of FIB in other
recreational sands (i.e., sandboxes and playgrounds). In this study, different
culture-based FIB enumeration techniques were compared and microbial source
tracking assays were conducted on recreational sand samples from beaches,
playgrounds and sandboxes around Toronto, ON. FIB were detected in every sand
sample (n=104) with concentrations not changing significantly over the five month
sampling period. Concentrations of FIB and a gull-specific DNA marker were
significantly higher in foreshore beach sands, and indicated these were a more
significant reservoir of FIB contamination than sandbox or playground sands.
Human- and dog-specific contamination markers were not detected. All culture
based FIB enumeration techniques were consistent in identifying the elevated FIB
concentrations associated with foreshore beach sands. However, significant
differences between differential agar media, IDEXX and Aquagenx Compartment Bag
Test were observed, with DC media and Enterolert being the most sensitive methods
to detect Escherichia coli and enterococci, respectively. To better understand
the elevated occurrence of E. coli in foreshore sands, microcosm survival
experiments were conducted at two different temperatures (15 degrees C and 28
degrees C) using non-sterile saturated foreshore beach sands collected from two
urban freshwater beaches with different sand type (fine grain and sand-cobble).
Microcosms were inoculated with a mixture of eight sand-derived E. coli strains
and sampled over a 28-day period. E. coli levels were found to decline in all
microcosms, although survival was significantly greater in the finer sand and at
the cooler temperature (15 degrees C). These results indicate that FIB can be
widespread in any type of recreational sand and, while E. coli can survive for
many weeks, it is most likely to accumulate in cooler fine-grain sand as occurs
below the foreshore sand surface.
PMID- 26432163
TI - Clinical Practice Guidelines for the Management of Gastroesophageal Reflux and
Gastroesophageal Reflux Disease: 1 Year to 18 Years of Age.
PMID- 26432164
TI - The regulatory roles of non-coding RNAs in nerve injury and regeneration.
AB - Non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long non-coding RNAs
(lncRNAs), have attracted much attention since their regulatory roles in diverse
cell processes were recognized. Emerging studies demonstrate that many ncRNAs are
differentially expressed after injury to the nervous system, significantly
affecting nerve regeneration. In this review, we compile the miRNAs and lncRNAs
that have been reported to be dysregulated following a variety of central and
peripheral nerve injuries, including acquired brain injury, spinal cord injury,
and peripheral nerve injury. We also list investigations on how these miRNAs and
lncRNAs exert the regulatory actions in neurodegenerative and neuroregenerative
processes through different mechanisms involving their interaction with target
coding genes. We believe that comprehension of the expression profiles and the
possible functions of ncRNAs during the processes of nerve injury and
regeneration will help understand the molecular mechanisms responsible for post
nerve-injury changes, and may contribute to the potential use of ncRNAs as a
diagnostic marker and therapeutic target for nerve injury.
PMID- 26432165
TI - Atypical presentation of Charcot-Marie-Tooth disease 1A: A case report.
AB - Charcot-Marie-Tooth (CMT) 1A is the most common form of CMT disease and is
characterized by duplication of Peripheral myelin protein 22 (PMP22) gene. We
report a boy with genetically confirmed CMT1A disease having clinical involvement
of hypoglossal and glossopharyngeal nerves, as well as asymmetrical and primarily
upper limb involvement. These atypical features widen the clinical spectrum of
CMT1A, leading to interesting observations about PMP22 gene related disorders and
varied clinical expression of similar genetic mutations.
PMID- 26432166
TI - Tebuconazole disrupts steroidogenesis in Xenopus laevis.
AB - A 27-day controlled exposure study of adult male African clawed frogs (Xenopus
laevis) was conducted to examine the mechanism by which tebuconazole may disrupt
steroidogenesis. The fungicide was measured by LC-MS/MS in tank water and in
target tissues (adipose, kidney, liver, and brain), and we observed tissue
specific bioconcentration with BCF up to 238. Up to 10 different steroid hormones
were quantified in gonads using LC-MS/MS and in plasma using GC-MS/MS and a
radioimmunoassay was performed for further measurement of androgens. In order to
assess whether effects increased with exposure or animals adapted to the
xenobiotic, blood samples were collected 12 days into the study and at
termination (day 27). After 12 days of exposure to 100 and 500MUgL(-1)
tebuconazole, plasma levels of testosterone (T) and dihydrotestosterone (DHT)
were increased, while plasma 17beta-estradiol (E2) concentrations were greatly
reduced. Exposure to 0.1MUgL(-1), on the other hand, resulted in decreased levels
of T and DHT, with no effects observed for E2. After 27 days of exposure, effects
were no longer observed in circulating androgen levels while the suppressive
effect on E2 persisted in the two high-exposure groups (100 and 500MUgL(-1)).
Furthermore, tebuconazole increased gonadal concentrations of T and DHT as well
as expression of the enzyme CYP17 (500MUgL(-1), 27 days). These results suggest
that tebuconazole exposure may supress the action of CYP17 at the lowest exposure
(0.1MUgL(-1)), while CYP19 suppression dominates at higher exposure
concentrations (increased androgens and decreased E2). Increased androgen levels
in plasma half-way into the study and in gonads at termination may thus be
explained by compensatory mechanisms, mediated through increased enzymatic
expression, as prolonged exposure had no effect on circulating androgen levels.
PMID- 26432167
TI - Associations between the neighbourhood built environment and out of school
physical activity and active travel: An examination from the Kids in the City
study.
AB - This study's aim was to examine selected objectively-measured and child specific
built environment attributes in relation to proportion of out-of-school time
spent in moderate-to-vigorous physical activity (%MVPA) and active travel in a
group of ethnically and socio-economically diverse children (n=236) living in
Auckland, New Zealand. Street connectivity and distance to school were related to
the proportion of trips made by active modes. Ratio of high speed to low speed
roads and improved streetscape for active travel were related to %MVPA on
weekdays only. Inconsistent results were found for destination accessibility.
Local destinations (particularly schools) along a safe street network may be
important for encouraging children's activity behaviours.
PMID- 26432168
TI - Uncovering the function of Disrupted in Schizophrenia 1 through interactions with
the cAMP phosphodiesterase PDE4: Contributions of the Houslay lab to molecular
psychiatry.
AB - Nearly 10years ago the laboratory of Miles Houslay was part of a collaboration
which identified and characterized the interaction between Disrupted in
Schizophrenia 1 and phosphodiesterase type 4. This work has had significant
impact on our thinking of psychiatric illness causation and the potential for
therapeutics.
PMID- 26432169
TI - Phosphoinositide-dependent kinase-1 inhibits TRAF6 ubiquitination by interrupting
the formation of TAK1-TAB2 complex in TLR4 signaling.
AB - Phosphoinositide-dependent protein kinase 1 (PDK1) plays a key role in the
phosphoinositide 3-kinase (PI3K)-PDK1-Akt pathway that induces cell survival and
cardiovascular protections through anti-apoptosis, vasodilation, anti
inflammation, and anti-oxidative stress activities. Although several reports have
proposed the negative role of PDK1 in Toll-like receptor 4 (TLR4) signaling, the
molecular mechanism is still unknown. Here we show that PDK1 inhibits tumor
necrosis factor (TNF) receptor-associated factor 6 (TRAF6) ubiquitination by
interrupting the complex between transforming growth factor beta-activated kinase
1 (TAK1) and TAK1 binding protein 2 (TAB2), which negatively regulates TAK1
activity. The overexpression of PDK1 in 293/TLR4 cells resulted in suppressions
of nuclear factor kappa B (NF-kappaB) activation and production of
proinflammatory cytokines including interleukin (IL)-6 and TNF-alpha in response
to lipopolysaccharide stimulation. Conversely, THP-1 human monocytes transiently
cultured in low glucose medium displayed down-regulated PDK1 expression, and
significantly enhanced TLR4-mediated signaling for the activation of NF-kappaB,
demonstrating a negative role of PDK1. Biochemical studies revealed that PDK1
significantly interacted with TAK1, resulting in the inhibition of the
association of TAB2 with TAK1, which led to the attenuation of TRAF6
ubiquitination. Moreover, PDK1-knockdown THP-1 cells displayed enhancement of
downstream signals, activation of NF-kappaB, and increased production of pro
inflammatory cytokines IL-6, IL-1beta, and TNF-alpha, which potentially led to
the up-regulation of NF-kappaB-dependent genes in response to TLR4 stimulation.
Collectively, the results demonstrate that PDK1 inhibits the formation of the
TAK1-TAB2-TRAF6 complex and leads to the inhibition of TRAF6 ubiquitination,
which negatively regulates the TLR4-mediated signaling for NF-kappaB activation.
PMID- 26432170
TI - Distinct biological activity of threonine monophosphorylated MAPK isoforms during
the stress response in fission yeast.
AB - Mitogen-activated protein kinases (MAPKs) define a specific group of eukaryotic
protein kinases which regulate a number of cellular functions by transducing
extracellular signals to intracellular responses. Unlike other protein kinases,
catalytic activation of MAPKs by MAPKKs depends on dual phosphorylation at two
tyrosine and threonine residues within the conserved TXY motif, and this has been
proposed to occur in an ordered fashion, where the initial phosphorylation on
tyrosine is followed by phosphorylation at the threonine residue. However,
monophosphorylated MAPKs also exist in vivo, and although threonine
phosphorylated isoforms retain some catalytic activity, their functional
significance remains to be further elucidated. In the fission yeast
Schizosaccharomyces pombe MAPKs Sty1 and Pmk1 control multiple aspects of fission
yeast life cycle, including morphogenesis, cell cycle, and cellular response to a
variety of stressful situations. In this work we show that a trapping mechanism
increases MAPKK binding and tyrosine phosphorylation of both Sty1 and Pmk1 when
subsequent phosphorylation at threonine is hampered, indicating that a sequential
and likely processive mechanism might be responsible for MAPK activation in this
simple organism. Whereas threonine-monophosphorylated Sty1 showed a limited
biological activity particularly at the transcriptional level, threonine
monophosphorylated Pmk1 was able to execute most of the biological functions of
the dually phosphorylated kinase. Thus, threonine monophosphorylated MAPKs might
display distinct functional relevance among eukaryotes.
PMID- 26432171
TI - p62/SQSTM1 functions as a signaling hub and an autophagy adaptor.
AB - p62/SQSTM1 is a stress-inducible cellular protein that is conserved among
metazoans but not in plants and fungi. p62/SQSTM1 has multiple domains that
mediate its interactions with various binding partners and it serves as a
signaling hub for diverse cellular events such as amino acid sensing and the
oxidative stress response. In addition, p62/SQSTM1 functions as a selective
autophagy receptor for degradation of ubiqutinated substrates. In the present
review, we describe the current knowledge about p62 with regard to mammalian
target of rapamycin complex 1 activation, the Keap1-Nrf2 pathway and selective
autophagy.
PMID- 26432172
TI - Prediction of treatment discontinuation and recovery from Borderline Personality
Disorder: Results from an RCT comparing Schema Therapy and Transference Focused
Psychotherapy.
AB - Knowing what predicts discontinuation or success of psychotherapies for
Borderline Personality Disorder (BPD) is important to improve treatments. Many
variables have been reported in the literature, but replication is needed and
investigating what therapy process underlies the findings is necessary to
understand why variables predict outcome. Using data of an RCT comparing Schema
Therapy and Transference Focused Psychotherapy as treatments for BPD, variables
derived from the literature were tested as predictors of discontinuation and
treatment success. Participants were 86 adult outpatients (80 women, mean age
30.5 years) with a primary diagnosis of BPD who had on average received 3
previous treatment modalities. First, single predictors were tested with logistic
regression, controlling for treatment type (and medication use in case of
treatment success). Next, with multivariate backward logistic regression
essential predictors were detected. Baseline hostility and childhood physical
abuse predicted treatment discontinuation. Baseline subjective burden of
dissociation predicted a smaller chance of recovery. A second study demonstrated
that in-session dissociation, assessed from session audiotapes, mediated the
observed effects of baseline dissociation on recovery, indicating that
dissociation during sessions interferes with treatment effectiveness. The results
suggest that specifically addressing high hostility, childhood abuse, and in
session dissociation might reduce dropout and lack of effectiveness of treatment.
PMID- 26432173
TI - Predictors of response to CBT and IPT for depression; the contribution of therapy
process.
AB - Little is known about the factors that contribute to a positive psychotherapy
outcome. There is still considerable debate as to whether specific factors (e.g.
severity of symptoms, comorbidity) or nonspecific factors (e.g. alliance, therapy
process) are most important in influencing outcome. This study examined the
additional contribution that therapeutic process and alliance made to previously
identified specific predictors of response to CBT and IPT for depression over the
course of therapy. The previously identified specific factors were belief that
childhood reasons caused the depression, recurrent depression, perceptions about
how logical therapy was and comorbid personality disorder symptoms. One hundred
and sixty five adult outpatients with major depression were treated for
depression in a randomised clinical trial examining predictors of response to
Cognitive Behavior Therapy and Interpersonal Psychotherapy. All therapy sessions
were audiorecorded to enable objective ratings of therapeutic process and
alliance. Process factors - patient psychic distress, patient participation and
patient alliance had the strongest associations with outcome. The early and
middle stage of therapy process did not account for any additional variance other
than that previously identified by the patient predictors, however, at the end
stage of therapy process contributed a further 14%.
PMID- 26432175
TI - Commitment questions targeting patients promotes uptake of under-used health
services: Findings from a national quality improvement program in Australia.
AB - RATIONALE: Interventions asking patients to commit to speaking with their doctor
about a health-related issue could be used to improve quality of care. OBJECTIVE:
To evaluate the impact of commitment questions targeting patients on the uptake
of recommended health services within a national quality improvement program
(Veterans' MATES). METHODS: Patients targeted in the home medicines reviews
(HMRs), dose administration aids (DAAs), renal function testing and diabetes
interventions were posted educational information and response forms which asked
whether they intended to talk to their general practitioner (GP) about the
targeted service. Uptake of the service after each intervention was determined
using health claims data. Log binomial regression models compared the monthly
rate of service use in the nine months post-intervention among patients answering
'yes' to a commitment question with non-responders and patients answering 'no' or
'unsure'. RESULTS: Each intervention targeted up to 58,000 patients. The average
response rate was 28%. Positive responses were associated with increased uptake
of HMRs (rate ratio (RR) 2.64, 95% CI 2.39-2.92; p < 0.0001), dose administration
aids (RR 2.53, 95% CI 2.29-2.79; p < 0.0001), renal function tests (RR 1.18, 95%
CI 1.13-1.24; p < 0.0001), GP management plans (RR 1.30, 95% CI 1.14-1.48; p <
0.0001) and diabetes care plans (RR 1.47, 95% CI 1.24-1.75; p < 0.0001) compared
to non-responders. Similar increases in uptake were also observed among positive
responders when compared to patients responding 'no' or 'unsure' to the
commitment question. CONCLUSION: Positive responses to commitment questions
distributed as part of national, multifaceted interventions were consistently
associated with increased uptake of targeted services.
PMID- 26432176
TI - Controlled but not cured: Structural processes and explanatory models of Chagas
disease in tropical Bolivia.
AB - Dressler (2001:456) characterizes medical anthropology as divided between two
poles: the constructivist, which focuses on the "meaning and significance that
events have for people," and the structuralist, which emphasizes socioeconomic
processes and relationships. This study synthesizes structuralist and
constructivist perspectives by investigating how structural processes impact
explanatory models of Chagas disease in a highly endemic area. The research took
place from March-June 2013 through the Centro Medico Humberto Parra, a non-profit
clinic servicing low income populations in Palacios, Bolivia and surrounding
communities. Semistructured interviews (n = 68) and consensus analysis
questionnaires (n = 48) were administered to people dealing with Chagas disease.
In the interview narratives, respondents link Chagas disease with experiences of
marginalization and rural poverty, and describe multilayered impediments to
accessing treatment. They often view the disease as incurable, but this reflects
inconsistent messages from the biomedical system. The consensus analysis results
show strong agreement on knowledge of the vector, ethnomedical treatment, and
structural factors related to Chagas disease. In interpreting Chagas disease,
respondents account for the structural factors which place them at risk and
impede access to care.
PMID- 26432174
TI - Cocaine choice procedures in animals, humans, and treatment-seekers: Can we
bridge the divide?
AB - Individuals with cocaine use disorder chronically self-administer cocaine to the
detriment of other rewarding activities, a phenomenon best modeled in laboratory
drug-choice procedures. These procedures can evaluate the reinforcing effects of
drugs versus comparably valuable alternatives under multiple behavioral
arrangements and schedules of reinforcement. However, assessing drug-choice in
treatment-seeking or abstaining humans poses unique challenges: for ethical
reasons, these populations typically cannot receive active drugs during research
studies. Researchers have thus needed to rely on alternative approaches that
approximate drug-choice behavior or assess more general forms of decision-making,
but whether these alternatives have relevance to real-world drug-taking that can
inform clinical trials is not well-understood. In this mini-review, we (A)
summarize several important modulatory variables that influence cocaine choice in
nonhuman animals and non-treatment seeking humans; (B) discuss some of the
ethical considerations that could arise if treatment-seekers are enrolled in drug
choice studies; (C) consider the efficacy of alternative procedures, including
non-drug-related decision-making and 'simulated' drug-choice (a choice is made,
but no drug is administered) to approximate drug choice; and (D) suggest
opportunities for new translational work to bridge the current divide between
preclinical and clinical research.
PMID- 26432177
TI - [Facial palsy sequel and botulinum toxin].
AB - Medical treatment of facial paralysis sequel is an essential part of the overall
management of this pathology. The use of botulinum toxin has revolutionized
results in greatly improving facial symmetry. The toxin can be used either the
healthy side of the face by treating the compensatory hyperactivity of non
paralyzed side of the face or the paralyzed side (in the spastic forms) to treat
synkinesis and spasms of the face on the pathologic side. This treatment course
will be complemented by the rest of the therapeutic, i.e. rehabilitation and
surgical treatment.
PMID- 26432178
TI - Diethylcarbamazine citrate ameliorates insulin resistance in high-fat diet
induced obese mice via modulation of adipose tissue inflammation.
AB - Diethylcarbamazine citrate (DEC) had been known as anti-inflammatory drug but its
effect on obesity-induced insulin resistance as a result of released inflammatory
mediators from adipose tissue (AT) was not known. White male albino mice were fed
with high fat diet (HFD) for 18weeks to induce obesity. DEC at different three
doses (12, 50 and 200mg/kg) was orally administered twice a week starting at week
6. Body, liver and adipose tissue weights were taken, while glucose tolerance,
insulin resistance, blood triglycerides and levels of adipokines (leptin, TNF
alpha, IL-6 and MCP-1) were tested. The activity of cyclooxygenase (COX) in the
liver tissue homogenate was also tested. In addition, NF-kappaBp65 localization
in liver cell cytoplasmic and nuclear fractions was detected using Western
blotting. The only effective anti-inflammatory dose was 50mg/kg to reduce
(p<0.05) the high levels of glucose, insulin and triglycerides in serum. DEC was
not anti-obesity drug because the weights of body, liver and adipose tissues were
not changed. Hyperleptinemia was decreased (p<0.001) and associated with a
reduction in serum levels of TNF-alpha, IL-6 and MCP-1 (p<0.001). In addition,
the activity of COX in DEC treatment decreased significantly (p<0.01), while NF
kappaBp65 localization in nuclear extracts was obviously inhibited in 50mg/kg
treated group. It could be concluded that DEC was the only effective dose against
mouse insulin resistance but not lipid accumulation.
PMID- 26432179
TI - Linalool inhibits cigarette smoke-induced lung inflammation by inhibiting NF
kappaB activation.
AB - Linalool, a natural compound that exists in the essential oils of several
aromatic plants species, has been reported to have anti-inflammatory effects.
However, the effects of linalool on cigarette smoke (CS)-induced acute lung
inflammation have not been reported. In the present study, we investigated the
protective effects of linalool on CS-induced acute lung inflammation in mice.
Linalool was given i.p. to mice 2h before CS exposure daily for five consecutive
days. The numbers of macrophages and neutrophils in bronchoalveolar lavage fluid
(BALF) were measured. The production of TNF-alpha, IL-6, IL-1beta, IL-8 and MCP-1
were detected by ELISA. The expression of NF-kappaB was detected by Western
blotting. Our results showed that treatment of linalool significantly attenuated
CS-induced lung inflammation, coupled with inhibited the infiltration of
inflammatory cells and TNF-alpha, IL-6, IL-1beta, IL-8 and MCP-1 production.
Meanwhile, treatment of linalool inhibited CS-induced lung MPO activity and
pathological changes. Furthermore, linalool suppressed CS-induced NF-kappaB
activation in a dose-dependent manner. In conclusion, our results demonstrated
that linalool protected against CS-induced lung inflammation through inhibiting
CS-induced NF-kappaB activation.
PMID- 26432180
TI - Attention capacities of preterm and term born toddlers: A multi-method approach.
AB - OBJECTIVE: Many preterm children show difficulties in attention at (pre)school
age. The development of attention capacities of preterm and term toddlers was
compared using a longitudinal and multi-method approach at 12, 18 and 24months.
METHOD: Attention was measured for 123 preterm (32-36weeks gestation) and 101
term born children, using eye tracking (18months), observations during mother
child interaction (18months), and mother-reports (12, 18, and 24months). RESULTS:
Preterm toddlers had lower scores than term children on the eye-tracking measures
of orienting and alerting. No group differences were found with observations,
mother-reports, and the eye-tracking measure of executive attention. More preterm
than term children had suboptimal scores on measures of the alerting system at
18months, possibly indicating difficulties in attention development. CONCLUSION:
Preterm children showed an increased risk for suboptimal functioning in alerting
attention capacities, as early as at a toddler age.
PMID- 26432181
TI - Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of
chronic migraine: a multicentre, randomised, double-blind, placebo-controlled,
phase 2b study.
AB - BACKGROUND: Benefits of calcitonin-gene related peptide (CGRP) inhibition have
not been established in chronic migraine. Here we assess the safety,
tolerability, and efficacy of two doses of TEV-48125, a monoclonal anti-CGRP
antibody, in the preventive treatment of chronic migraine. METHODS: In this
multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel
group phase 2b study, we enrolled men and women (aged 18-65 years) from 62 sites
in the USA who had chronic migraine. Using a randomisation list generated by a
central computerised system and an interactive web response system, we randomly
assigned patients (1:1:1, stratified by sex and use of concomitant preventive
drugs) to three 28-day treatment cycles of subcutaneous TEV-48125 675/225 mg (675
mg in the first treatment cycle and 225 mg in the second and third treatment
cycles), TEV-48125 900 mg (900 mg in all three treatment cycles), or placebo.
Investigators, patients, and the funder were blinded to treatment allocation.
Daily headache information was captured using an electronic diary. Primary
endpoints were change from baseline in the number of headache-hours during the
third treatment cycle (weeks 9-12) and safety and tolerability during the study.
Secondary endpoint was change in the number of moderate or severe headache-days
in weeks 9-12 relative to baseline. Efficacy endpoints were analysed for the
intention-to-treat population. Safety and tolerability were analysed using
descriptive statistics. This trial is registered with ClinicalTrials.gov, number,
NCT02021773. FINDINGS: Between Jan 8, 2014, and Aug 27, 2014, we enrolled 264
participants: 89 were randomly assigned to receive placebo, 88 to receive 675/225
mg TEV-48125, and 87 to receive 900 mg TEV-48125. The mean change from baseline
in number of headache-hours during weeks 9-12 was -59.84 h (SD 80.38) in the
675/225 mg group and -67.51 h (79.37) in the 900 mg group, compared with -37.10 h
(79.44) in the placebo group. The least square mean difference in the reduction
of headache-hours between the placebo and 675/225 mg dose groups was -22.74 h
(95% CI -44.28 to -1.21; p=0.0386), whereas the difference between placebo and
900 mg dose groups was -30.41 h (-51.88 to -8.95; p=0.0057). Adverse events were
reported by 36 (40%) patients in the placebo group, 47 (53%) patients in the
675/225 mg dose group, and 41 (47%) patients in the 900 mg dose group, whereas
treatment-related adverse events were recorded in 15 (17%) patients, 25 (29%)
patients, and 28 (32%) patients, respectively. The most common adverse events
were mild injection-site pain and pruritus. Four (1%) patients had serious non
treatment-related adverse events (one patient in the placebo group, one patient
in the 675/225 mg group, and two patients in the 900 mg group); no treatment
related adverse events were serious and there were no relevant changes in blood
pressure or other vital signs. INTERPRETATION: TEV-48125 given by subcutaneous
injection every 28 days seems to be tolerable and effective, thus supporting the
further development of TEV-48125 for the preventive treatment of chronic migraine
in a phase 3 trial. FUNDING: Teva Pharmaceuticals.
PMID- 26432183
TI - CGRP antibodies: the Holy Grail for migraine prevention?
PMID- 26432184
TI - Recurrent Clostridium difficile infection in intensive care unit patients.
AB - BACKGROUND: The purpose of this study was to assess the 12-week cumulative
incidence of recurrent Clostridium difficile infection (rCDI) and identify risk
factors for rCDI in patients that acquired index C difficile infection (CDI)
while in the intensive care unit (ICU). METHODS: This retrospective single-center
cohort study reviewed adult patients from 6 different ICUs who developed a CDI
between February 2010 and September 2013. RESULTS: Out of 162 included ICU
patients, 34 experienced rCDI. Risk of rCDI was higher in the ICU versus non-ICU
group (21% vs 17%, P = .03). The incidence of rCDI was highest in the surgical
intensive care unit (SICU) at 43.8%. A multivariable logistic regression model
was constructed and identified 5 significant risk factors for rCDI: previous CDI
(odds ratio [OR], 8.03; 95% confidence interval [CI], 1.90-34.02; P = .005),
log10 ICU length of stay in days (OR, 3.67; 95% CI, 1.13-11.85; P = .03),
acquisition of CDI in the medical intensive care unit (MICU) (OR, 5.35; 95% CI,
1.60-17.85; P = .006) or SICU (OR, 15.30; 95% CI, 4.09-57.23; P < .001), and
chronic obstructive pulmonary disease (COPD) (OR, 3.55; 95% CI, 1.41-8.94; P =
.007). CONCLUSION: ICU adults had a significantly higher 12-week incidence of
rCDI than non-ICU patients. Risk factors for rCDI after acquisition of infection
in an ICU include MICU and SICU patients, previous CDI, COPD, and length of stay.
PMID- 26432182
TI - Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high
frequency episodic migraine: a multicentre, randomised, double-blind, placebo
controlled, phase 2b study.
AB - BACKGROUND: Calcitonin gene-related peptide (CGRP) is a validated target for the
treatment of episodic migraine. Here we assess the safety, tolerability, and
efficacy of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive
treatment of high-frequency episodic migraine. METHODS: In this multicentre,
randomised, double-blind, placebo-controlled, phase 2b study, we enrolled men and
women (aged 18-65 years) from 62 sites in the USA who had migraine headaches 8-14
days per month. Using a randomisation list generated by a central computerised
system and an interactive web response system, we randomly assigned patients
(1:1:1; stratified by sex and use of concomitant preventive drugs) after a 28 day
run-in period to three 28 day treatment cycles of subcutaneous 225 mg TEV-48125,
675 mg TEV-48125, or placebo. Investigators, patients, and the funder were
blinded to treatment allocation. Patients reported headache information daily
using an electronic diary. Primary endpoints were change from baseline in
migraine days during the third treatment cycle (weeks 9-12) and safety and
tolerability. The secondary endpoint was change relative to baseline in headache
days during weeks 9-12. Efficacy endpoints were analysed for the intention-to
treat population. Safety and tolerability were analysed using descriptive
statistics. This trial is registered at ClinicalTrials.gov, number NCT02025556.
FINDINGS: Between Jan 8, 2014, and Oct 15, 2014, we enrolled 297 participants:
104 were randomly assigned to receive placebo, 95 to receive 225 mg TEV-48125,
and 96 to receive 675 mg TEV-48125. The least square mean (LSM) change in number
of migraine-days from baseline to weeks 9-12 was -3.46 days (SD 5.40) in the
placebo group, -6.27 days (5.38) in the 225 mg dose group, and -6.09 days (5.22)
in the 675 mg dose group. The LSM difference in the reduction of migraine-days
between the placebo and 225 mg dose groups was -2.81 days (95% CI -4.07 to -1.55;
p<0.0001), whereas the difference between the placebo and 675 mg dose group was
2.64 days (-3.90 to -1.38; p<0.0001). LSM differences in the reduction of
headache-days were -2.63 days (-3.91 to -1.34; p<0.0001) between the placebo
group and 225 mg dose group and -2.58 days (-3.87 to 1.30; p <0.0001) between the
placebo group and the 675 mg dose group. Adverse events occurred in 58 (56%)
patients in the placebo group, 44 (46%) patients in the 225 mg dose group, and 57
(59%) patients in the 675 mg dose group; moderate or severe adverse events were
reported for 29 (27%) patients, 24 (25%) patients, and 26 (27%) patients,
respectively. INTERPRETATION: TEV-48125, at doses of 225 mg and 675 mg given once
every 28 days for 12 weeks, was safe, well tolerated, and effective as a
preventive treatment of high-frequency episodic migraine, thus supporting
advancement of the clinical development programme to phase 3 clinical trials.
FUNDING: Teva Pharmaceuticals.
PMID- 26432185
TI - Cost-effectiveness of a hand hygiene program on health care-associated infections
in intensive care patients at a tertiary care hospital in Vietnam.
AB - BACKGROUND: The cost-effectiveness of a hand hygiene (HH) program in low- and
middle-income countries (LMICs) is largely unknown. We assessed the cost
effectiveness of a HH program in a large tertiary Vietnamese hospital. METHODS:
This was a before and after study of a hand hygiene program where HH compliance,
incidence of hospital-acquired infections (HAIs), and costs were analyzed.The HH
program was implemented in 2 intensive care and 15 critical care units. The
program included upgrading HH facilities, providing alcohol-based handrub at
point of care, HH campaigns, and continuous HH education. RESULTS: The HH
compliance rate increased from 25.7% to 57.5% (P < .001). The incidence of
patients with HAI decreased from 31.7% to 20.3% (P < .001) after the
intervention. The mean cost for patients with HAI was $1,908, which was 2.5 times
higher than the costs for patients without an HAI. The mean attributable cost of
an HAI was $1,131. The total cost of the HH program was $12,570, which equates to
a per-patient cost of $6.5. The cost-effectiveness was estimated at -$1,074 or
$1,074 saved per HAI prevented. The intervention remained cost savings under
various scenarios with lower HAI rates. CONCLUSION: The HH program is an
effective strategy in reducing the incidence of HAIs in intensive care units and
is cost-effective in Vietnam. HH programs need to be encouraged across Vietnam
and other LMICs.
PMID- 26432186
TI - Responses of peripheral blood mononuclear cells to moderate exercise and hypoxia.
AB - The purpose of this study was to analyze the physiological features of peripheral
blood mononuclear cells (PBMCs) isolated from healthy female trekkers before and
after physical activity carried out under both normoxia (low altitude, < 2000 m
a.s.l.) and hypobaric hypoxia (high altitude, > 3700 m a.s.l.). The experimental
design was to differentiate effects induced by exercise and those related to
external environmental conditions. PBMCs were isolated from seven female subjects
before and after each training period. The PBMCs were phenotypically and
functionally characterized using fluorimetric and densitometric analyses, to
determine cellular activation, and their intracellular Ca(2+) levels and
oxidative status. After a period of normoxic physical exercise, the PBMCs showed
an increase in fully activated T lymphocytes (CD3(+) CD69(+) ) and a reduction in
intracellular Ca(2+) levels. On the other hand, with physical exercise performed
under hypobaric hypoxia, there was a reduction in T lymphocytes and an increase
in nonactivated B lymphocytes, accompanied by a reduction in O2 (-) levels in the
mitochondria. These outcomes reveal that in women, low- to moderate-intensity
aerobic trekking induces CD69 T cell activation and promotes anti-stress effects
on the high-altitude-induced impairment of the immune responses and the oxidative
balance.
PMID- 26432188
TI - Variation in Lung Tumour Breathing Motion between Planning Four-dimensional
Computed Tomography and Stereotactic Ablative Radiotherapy Delivery and its
Dosimetric Implications: Any Role for Four-dimensional Set-up Verification?
AB - AIMS: To investigate variation in tumour breathing motion (TBM) between the
planning four-dimensional computed tomograph (4DCT) and treatment itself for
primary or secondary lung tumours undergoing stereotactic ablative radiotherapy
(SABR). MATERIALS AND METHODS: Sixteen consecutive patients underwent planning
4DCT at least 1 week after implantation of a fiducial marker. The maximal extent
of breathing motion of the intra-tumoural fiducial was measured at 4DCT and again
at delivery of each SABR fraction on the linac using stereoscopic kilovoltage
imaging. Displacements of the fiducial beyond planned limits were measured in
three dimensions and represented as vectors. Variation in breathing motion
between the planning 4DCT and treatment, and between individual SABR fractions
was analysed. RESULTS: Although TBM at treatment exceeded planned tumour motion
limits for at least part of the course for all patients, 31% of patients remained
consistently within 1 mm, 50% within 2 mm and 69% consistently within 3 mm of
planned parameters. However, 19% of patients experienced TBM variation 5 mm or
more beyond planned limits for at least one fraction. For all patients, the
median displacement vector at treatment beyond the planned motion envelope was
1.0 mm (mean 2.0 mm, range 0-12.7 mm). Variation in TBM at treatment from 4DCT
correlated neither with the magnitude of TBM at 4DCT nor with planning target
volume size (rs = 0.13, P = 0.62; rs = 0.02, P = 0.94, respectively). Nor was TBM
variation related to tumour type or lobar position (P = 0.35, P = 0.06,
respectively). Inter-fraction TBM variation was modest, with an average standard
deviation of 1.7 mm (0.3-8.7 mm). CONCLUSIONS: TBM variation between 4DCT and
treatment and between SABR fractions was modest for most patients. However, 19%
of patients experienced significant TBM variation that could be clinically
relevant for those most severely affected. It seems prudent to carry out on-couch
assessment of TBM at each SABR fraction to identify such patients who might
benefit from respiratory gating or adaptive radiotherapy to maintain tumour
motion within the planned limits.
PMID- 26432187
TI - Fiber ball imaging.
AB - By modeling axons as thin cylinders, it is shown that the inverse Funk transform
of the diffusion MRI (dMRI) signal intensity obtained on a spherical shell in q
space gives an estimate for a fiber orientation density function (fODF), where
the accuracy improves with increasing b-value provided the signal-to-noise ratio
is sufficient. The method is similar to q-ball imaging, except that the Funk
transform of q-ball imaging is replaced by its inverse. We call this new approach
fiber ball imaging. The fiber ball method is demonstrated for healthy human
brain, and fODF estimates are compared to diffusion orientation distribution
function (dODF) approximations obtained with q-ball imaging. The fODFs are seen
to have sharper features than the dODFs, reflecting an enhancement of the higher
degree angular frequencies. The inverse Funk transform of the dMRI signal
intensity data provides a simple and direct method of estimating a fODF. In
addition, fiber ball imaging leads to an estimate for the ratio of the fraction
of MRI visible water confined to the intra-axonal space divided by the square
root of the intra-axonal diffusivity. This technique may be useful for white
matter fiber tractography, as well as other types of microstructural modeling of
brain tissue.
PMID- 26432189
TI - Prescribed journeys through life: Cultural differences in mental time travel
between Middle Easterners and Scandinavians.
AB - Mental time travel is the ability to remember past events and imagine future
events. Here, 124 Middle Easterners and 128 Scandinavians generated important
past and future events. These different societies present a unique opportunity to
examine effects of culture. Findings indicate stronger influence of normative
schemas and greater use of mental time travel to teach, inform and direct
behaviour in the Middle East compared with Scandinavia. The Middle Easterners
generated more events that corresponded to their cultural life script and that
contained religious words, whereas the Scandinavians reported events with a more
positive mood impact. Effects of gender were mainly found in the Middle East.
Main effects of time orientation largely replicated recent findings showing that
simulation of future and past events are not necessarily parallel processes. In
accordance with the notion that future simulations rely on schema-based
construction, important future events showed a higher overlap with life script
events than past events in both cultures. In general, cross-cultural
discrepancies were larger in future compared with past events. Notably, the high
focus in the Middle East on sharing future events to give cultural guidance is
consistent with the increased adherence to normative scripts found in this
culture.
PMID- 26432190
TI - Optimized ultrasonic attenuation measures for non-homogeneous materials.
AB - In this paper the study of frequency-dependent ultrasonic attenuation in strongly
heterogeneous materials is addressed. To determine the attenuation accurately
over a wide frequency range, it is necessary to have suitable excitation
techniques. Three kinds of transmitted signals have been analysed, grouped
according to their bandwidth: narrowband and broadband signals. The mathematical
formulation has revealed the relation between the distribution of energy in their
spectra and their immunity to noise. Sinusoidal and burst signals have higher
signal-to-noise ratios (SNRs) but need many measurements to cover their frequency
range. However, linear swept-frequency signals (chirp) improve the effective
bandwidth covering a wide frequency range with a single measurement and
equivalent accuracy, at the expense of a lower SNR. In the case of highly
attenuating materials, it is proposed to use different configurations of chirp
signals, enabling injecting more energy, and therefore, improving the sensitivity
of the technique without a high time cost. Thus, if the attenuation of the
material and the sensitivity of the measuring equipment allows the use of
broadband signals, the combination of this kind of signal and suitable signal
processing results in an optimal estimate of frequency-dependent attenuation with
a minimum measurement time.
PMID- 26432191
TI - LAMTOR1-PRKCD and NUMA1-SFMBT1 fusion genes identified by RNA sequencing in
aneurysmal benign fibrous histiocytoma with t(3;11)(p21;q13).
AB - RNA sequencing of an aneurysmal benign fibrous histiocytoma with the karyotype
46,XY,t(3;11)(p21;q13),del(6)(p23)[17]/46,XY[2] showed that the t(3;11) generated
two fusion genes: LAMTOR1-PRKCD and NUMA1-SFMBT1. RT-PCR together with Sanger
sequencing verified the presence of fusion transcripts from both fusion genes. In
the LAMTOR1-PRKCD fusion, the part of the PRKCD gene coding for the catalytic
domain of the serine/threonine kinase is under control of the LAMTOR1 promoter.
In the NUMA1-SFMBT1 fusion, the part of the SFMBT1 gene coding for two of four
malignant brain tumor domains and the sterile alpha motif domain is controlled by
the NUMA1 promoter. The data support a neoplastic genesis of aneurysmal benign
fibrous histiocytoma and indicate a pathogenetic role for LAMTOR1-PRKCD and NUMA1
SFMBT1.
PMID- 26432192
TI - Biofilm formation is a risk factor for mortality in patients with Candida
albicans bloodstream infection-Scotland, 2012-2013.
AB - Bloodstream infections caused by Candida species remain a significant cause of
morbidity and mortality in hospitalized patients. Biofilm formation by Candida
species is an important virulence factor for disease pathogenesis. A prospective
analysis of patients with Candida bloodstream infection (n = 217) in Scotland
(2012-2013) was performed to assess the risk factors associated with patient
mortality, in particular the impact of biofilm formation. Candida bloodstream
isolates (n = 280) and clinical records for 157 patients were collected through
11 different health boards across Scotland. Biofilm formation by clinical
isolates was assessed in vitro with standard biomass assays. The role of biofilm
phenotype on treatment efficacy was also evaluated in vitro by treating preformed
biofilms with fixed concentrations of different classes of antifungal. Available
mortality data for 134 patients showed that the 30-day candidaemia case mortality
rate was 41%, with predisposing factors including patient age and catheter
removal. Multivariate Cox regression survival analysis for 42 patients showed a
significantly higher mortality rate for Candida albicans infection than for
Candida glabrata infection. Biofilm-forming ability was significantly associated
with C. albicans mortality (34 patients). Finally, in vitro antifungal
sensitivity testing showed that low biofilm formers and high biofilm formers were
differentially affected by azoles and echinocandins, but not by polyenes. This
study provides further evidence that the biofilm phenotype represents a
significant clinical entity, and that isolates with this phenotype differentially
respond to antifungal therapy in vitro. Collectively, these findings show that
greater clinical understanding is required with respect to Candida biofilm
infections, and the implications of isolate heterogeneity.
PMID- 26432193
TI - A virus-based nanoplasmonic structure as a surface-enhanced Raman biosensor.
AB - Fabrication of nanoscale structures with localized surface plasmons allows for
substantial increase in sensitivity of chem/bio sensors. The main challenge for
realizing complex nanoplasmonic structures in solution is the high level of
precision required at the nanoscale to position metal nanoparticles in 3D. In
this study, we report a virus-like particle (VLP) for building a 3D plasmonic
nanostructure in solution in which gold nanoparticles are precisely positioned on
the VLP by directed self-assembly techniques. These structures allow for
concentration of electromagnetic fields in the desired locations between the gold
nanoparticles or "hot spots". We measure the efficiency of the optical field
spatial concentration for the first time, which results in a ten-fold enhancement
of the capsid Raman peaks. Our experimental results agree with our 3D finite
element simulations. Furthermore, we demonstrate as a proof-of-principle that the
plasmonic nanostructures can be utilized in DNA detection down to 0.25 ng/MUl
(lowest concentration tested), while the protein peaks from the interior of the
nanoplasmonic structures, potentially, can serve as an internal tracer for the
biosensors.
PMID- 26432194
TI - Small biomolecule immunosensing with plasmonic optical fiber grating sensor.
AB - This study reports on the development of a surface plasmon resonance (SPR)
optical fiber biosensor based on tilted fiber Bragg grating technology for direct
detection of small biomarkers of interest for lung cancer diagnosis. Since SPR
principle relies on the refractive index modifications to sensitively detect mass
changes at the gold coated surface, we have proposed here a comparative study in
relation to the target size. Two cytokeratin 7 (CK7) samples with a molecular
weight ranging from 78 kDa to 2.6 kDa, respectively CK7 full protein and CK7
peptide, have been used for label-free monitoring. This work has first consisted
in the elaboration and the characterization of a robust and reproducible
bioreceptor, based on antibody/antigen cross-linking. Immobilized antibodies were
then utilized as binding agents to investigate the sensitivity of the biosensor
towards the two CK7 antigens. Results have highlighted a very good sensitivity of
the biosensor response for both samples diluted in phosphate buffer with a higher
limit of detection for the larger CK7 full protein. The most groundbreaking
nature of this study relies on the detection of small biomolecule CK7 peptides in
buffer and in the presence of complex media such as serum, achieving a limit of
detection of 0.4 nM.
PMID- 26432195
TI - Photoelectrochemical detection of enzymatically generated CdS nanoparticles:
Application to development of immunoassay.
AB - We report an innovative photoelectrochemical process (PEC) based on graphite
electrode modified with electroactive polyvinylpyridine bearing osmium complex
(Os-PVP). The system relies on the in situ enzymatic generation of CdS quantum
dots (QDs). Alkaline phosphatase (ALP) catalyzes the hydrolisis of sodium
thiophosphate (TP) to hydrogen sulfide (H2S) which in the presence Cd(2+) ions
yields CdS semiconductor nanoparticles (SNPs). Irradiation of SNPs with the
standard laboratory UV-illuminator (wavelength of 365 nm) results in
photooxidation of 1-thioglycerol (TG) mediated by Os-PVP complex on the surface
of graphite electrode at applied potential of 0.31 V vs. Ag/AgCl. A novel
immunoassay based on specific enzyme linked immunosorbent assay (ELISA) combined
with the PEC methodology was developed. Having selected the affinity interaction
between bovine serum albumine (BSA) with anti-BSA antibody (AB) as a model
system, we built the PEC immunoassay for AB. The new assay displays a linear
range up to 20 ngmL(-1) and a detection limit (DL) of 2 ngmL(-1) (S/N=3) which is
lower 5 times that of the traditional chromogenic ELISA test employing p-nitro
phenyl phosphate (pNPP).
PMID- 26432196
TI - Wrapping a facial nerve graft in a superficial temporofascial flap to optimise
vascularisation: technical note.
PMID- 26432197
TI - Current surgical management of metastases in the neck from mucosal squamous cell
carcinoma of the head and neck.
AB - Neck dissection, which is an important method of treatment for metastases from
mucosal (and other) squamous cell carcinomas (SCC) of the head and neck, is also
useful for staging disease. Since its inception it has changed from a radical to
a more conservative procedure, and vital structures are preserved wherever
possible. Refinements in methods of imaging to assess involvement in the neck
have encouraged alternative approaches that can improve outcomes and reduce
morbidity. We look at the reported evidence for the surgical management of
metastases in the neck from mucosal SCC.
PMID- 26432198
TI - Influence of education and diagnostic modes on glaucoma assessment by
optometrists.
AB - PURPOSE: To evaluate the influence of different clinical examination techniques,
including optic nerve head (ONH) photography, visual field tests, and adjunct
imaging on the diagnosis of glaucoma by Australian and New Zealand optometrists.
The effect of a short-term, didactic teaching module on these is also explored.
METHODS: Clinical data of 30 patients previously seen at the Centre for Eye
Health was collected and compiled into glaucoma diagnostic assessment modules.
Each of six modules contained different combinations of clinical examination
results and required a classification of the cases as normal, suspicious or
glaucoma. A cohort of 54 Australian and New Zealand optometrists were recruited
for the study and allocated into two cohorts. The intervention group completed a
glaucoma training course prior to the assessment while the control group
completed the assessment without additional training. Diagnostic accuracy was
compared between modules and optometrist groups. RESULTS: High false negative
rates were observed with ONH photography, which were drastically reduced with the
addition of visual field, albeit at the cost of increased false positive rates.
Addition of adjunct imaging techniques partially compensated for the increase in
the false positive rate from the visual field, but had limited effect on false
negative rate. Educational intervention resulted in larger improvement in the
diagnostic ability when multiple imaging modalities were provided. CONCLUSION:
The study highlighted the importance of combining both structural and functional
assessments in glaucoma. Current imaging technology demonstrated limited
usefulness for event diagnosis due to the persistent difficulties of defining
structural and functional loss in glaucoma, thus highlighting the need for new
glaucoma assessment techniques. Short-term didactic teaching programs may only
result in limited improvement of glaucoma diagnostic ability in optometrists, and
hence, it may need to be combined with long-term and/or non-didactic training
components to obtain a greater effect.
PMID- 26432199
TI - Paperless anesthesia: uses and abuses of these data.
AB - Demonstrably accurate records facilitate clinical decision making, improve
patient safety, provide better defense against frivolous lawsuits, and enable
better medical policy decisions. Anesthesia Information Management Systems (AIMS)
have the potential to improve on the accuracy and reliability of handwritten
records. Interfaces with electronic recording systems within the hospital or
wider community allow correlation of anesthesia relevant data with biochemistry
laboratory results, billing sections, radiological units, pharmacy, earlier
patient records, and other systems. Electronic storage of large and accurate
datasets has lent itself to quality assurance, enhancement of patient safety,
research, cost containment, scheduling, anesthesia training initiatives, and has
even stimulated organizational change. The time for record making may be
increased by AIMS, but in some cases has been reduced. The question of impact on
vigilance is not entirely settled, but substantial negative effects seem to be
unlikely. The usefulness of these large databases depends on the accuracy of data
and they may be incorrect or incomplete. Consequent biases are threats to the
validity of research results. Data mining of biomedical databases makes it easier
for individuals with political, social, or economic agendas to generate
misleading research findings for the purpose of manipulating public opinion and
swaying policymakers. There remains a fear that accessibility of data may have
undesirable regulatory or legal consequences. Increasing regulation of treatment
options during the perioperative period through regulated policies could reduce
autonomy for clinicians. These fears are as yet unsubstantiated.
PMID- 26432200
TI - Segmentation of retinal vessels by means of directional response vector
similarity and region growing.
AB - This paper presents a novel retinal vessel segmentation method. Opposed to the
general approach in similar directional methods, where only the maximal or summed
responses of a pixel are used, here, the directional responses of a pixel are
considered as a vector. The segmentation method is a unique region growing
procedure which combines a hysteresis thresholding scheme with the response
vector similarity of adjacent pixels. A vessel score map is constructed as the
combination of the statistical measures of the response vectors and its local
maxima to provide the seeds for the region growing procedure. A nearest neighbor
classifier based on a rotation invariant response vector similarity measure is
used to filter the seed points. Many techniques in the literature that capture
the Gaussian-like cross-section of vessels suffer from the drawback of giving
false high responses to the steep intensity transitions at the boundary of the
optic disc and bright lesions. To overcome this issue, we also propose a symmetry
constrained multiscale matched filtering technique. The proposed vessel
segmentation method has been tested on three publicly available image sets, where
its performance proved to be competitive with the state-of-the-art and comparable
to the accuracy of a human observer, as well.
PMID- 26432201
TI - Testing times.
PMID- 26432202
TI - Variety of life.
PMID- 26432203
TI - Goals galore.
PMID- 26432204
TI - Science must prepare for impact.
PMID- 26432216
TI - China to launch cap-and-trade system.
PMID- 26432217
TI - California faces arid future.
PMID- 26432218
TI - Brazilian science paralysed by economic slump.
PMID- 26432219
TI - Bacteria yield new gene cutter.
PMID- 26432220
TI - Gene-edited 'micropigs' to be sold as pets at Chinese institute.
PMID- 26432222
TI - Maths whizz solves a master's riddle.
PMID- 26432221
TI - Archimedes' legendary sphere brought to life.
PMID- 26432223
TI - The future of cryptocurrencies: Bitcoin and beyond.
PMID- 26432224
TI - Mountain battle.
PMID- 26432225
TI - Human Genome Project: Twenty-five years of big biology.
PMID- 26432226
TI - Modelling: Build imprecise supercomputers.
PMID- 26432234
TI - China: Ban unfair pricing of equipment imports.
PMID- 26432235
TI - Climate modelling: Community initiative tackles urban heat.
PMID- 26432236
TI - Plate tectonics: Continental-drift opus turns 100.
PMID- 26432237
TI - Global emissions: New oil investments boost carbon lock-in.
PMID- 26432238
TI - Environmental protection: US 'openness' bill is counterproductive.
PMID- 26432239
TI - Astrophysics: Primordial stars brought to light.
PMID- 26432241
TI - Neurodevelopmental disease: A molecular tightrope.
PMID- 26432242
TI - Condensed-matter Physics: Flat transistor defies the limit.
PMID- 26432243
TI - Human genomics: The end of the start for population sequencing.
PMID- 26432244
TI - CRISPR-Cas immunity in prokaryotes.
AB - Prokaryotic organisms are threatened by a large array of viruses and have
developed numerous defence strategies. Among these, only clustered, regularly
interspaced short palindromic repeat (CRISPR)-Cas systems provide adaptive
immunity against foreign elements. Upon viral injection, a small sequence of the
viral genome, known as a spacer, is integrated into the CRISPR locus to immunize
the host cell. Spacers are transcribed into small RNA guides that direct the
cleavage of the viral DNA by Cas nucleases. Immunization through spacer
acquisition enables a unique form of evolution whereby a population not only
rapidly acquires resistance to its predators but also passes this resistance
mechanism vertically to its progeny.
PMID- 26432247
TI - A subthermionic tunnel field-effect transistor with an atomically thin channel.
AB - The fast growth of information technology has been sustained by continuous
scaling down of the silicon-based metal-oxide field-effect transistor. However,
such technology faces two major challenges to further scaling. First, the device
electrostatics (the ability of the transistor's gate electrode to control its
channel potential) are degraded when the channel length is decreased, using
conventional bulk materials such as silicon as the channel. Recently, two
dimensional semiconducting materials have emerged as promising candidates to
replace silicon, as they can maintain excellent device electrostatics even at
much reduced channel lengths. The second, more severe, challenge is that the
supply voltage can no longer be scaled down by the same factor as the transistor
dimensions because of the fundamental thermionic limitation of the steepness of
turn-on characteristics, or subthreshold swing. To enable scaling to continue
without a power penalty, a different transistor mechanism is required to obtain
subthermionic subthreshold swing, such as band-to-band tunnelling. Here we
demonstrate band-to-band tunnel field-effect transistors (tunnel-FETs), based on
a two-dimensional semiconductor, that exhibit steep turn-on; subthreshold swing
is a minimum of 3.9 millivolts per decade and an average of 31.1 millivolts per
decade for four decades of drain current at room temperature. By using highly
doped germanium as the source and atomically thin molybdenum disulfide as the
channel, a vertical heterostructure is built with excellent electrostatics, a
strain-free heterointerface, a low tunnelling barrier, and a large tunnelling
area. Our atomically thin and layered semiconducting-channel tunnel-FET (ATLAS
TFET) is the only planar architecture tunnel-FET to achieve subthermionic
subthreshold swing over four decades of drain current, as recommended in ref. 17,
and is also the only tunnel-FET (in any architecture) to achieve this at a low
power-supply voltage of 0.1 volts. Our device is at present the thinnest-channel
subthermionic transistor, and has the potential to open up new avenues for ultra
dense and low-power integrated circuits, as well as for ultra-sensitive
biosensors and gas sensors.
PMID- 26432248
TI - Observed latitudinal variations in erosion as a function of glacier dynamics.
AB - Glacial erosion is fundamental to our understanding of the role of Cenozoic-era
climate change in the development of topography worldwide, yet the factors that
control the rate of erosion by ice remain poorly understood. In many tectonically
active mountain ranges, glaciers have been inferred to be highly erosive, and
conditions of glaciation are used to explain both the marked relief typical of
alpine settings and the limit on mountain heights above the snowline, that is,
the glacial buzzsaw. In other high-latitude regions, glacial erosion is presumed
to be minimal, where a mantle of cold ice effectively protects landscapes from
erosion. Glacial erosion rates are expected to increase with decreasing latitude,
owing to the climatic control on basal temperature and the production of
meltwater, which promotes glacial sliding, erosion and sediment transfer. This
relationship between climate, glacier dynamics and erosion rate is the focus of
recent numerical modelling, yet it is qualitative and lacks an empirical
database. Here we present a comprehensive data set that permits explicit
examination of the factors controlling glacier erosion across climatic regimes.
We report contemporary ice fluxes, sliding speeds and erosion rates inferred from
sediment yields from 15 outlet glaciers spanning 19 degrees of latitude from
Patagonia to the Antarctic Peninsula. Although this broad region has a relatively
uniform tectonic and geologic history, the thermal regimes of its glaciers range
from temperate to polar. We find that basin-averaged erosion rates vary by three
orders of magnitude over this latitudinal transect. Our findings imply that
climate and the glacier thermal regime control erosion rates more than do extent
of ice cover, ice flux or sliding speeds.
PMID- 26432250
TI - Correction.
PMID- 26432249
TI - Badges of distinction.
PMID- 26432246
TI - An integrated map of structural variation in 2,504 human genomes.
AB - Structural variants are implicated in numerous diseases and make up the majority
of varying nucleotides among human genomes. Here we describe an integrated set of
eight structural variant classes comprising both balanced and unbalanced
variants, which we constructed using short-read DNA sequencing data and
statistically phased onto haplotype blocks in 26 human populations. Analysing
this set, we identify numerous gene-intersecting structural variants exhibiting
population stratification and describe naturally occurring homozygous gene
knockouts that suggest the dispensability of a variety of human genes. We
demonstrate that structural variants are enriched on haplotypes identified by
genome-wide association studies and exhibit enrichment for expression
quantitative trait loci. Additionally, we uncover appreciable levels of
structural variant complexity at different scales, including genic loci subject
to clusters of repeated rearrangement and complex structural variants with
multiple breakpoints likely to have formed through individual mutational events.
Our catalogue will enhance future studies into structural variant demography,
functional impact and disease association.
PMID- 26432251
TI - Publishing: The journal that publishes no papers.
PMID- 26432252
TI - Neuroscience: Connectomes make the map.
PMID- 26432254
TI - Testing the mid-latitude hydrologic seesaw.
PMID- 26432255
TI - Woo et al. reply.
PMID- 26432256
TI - Outcomes of both abbreviated hyper-CVAD induction followed by autologous
hematopoietic cell transplantation and conventional chemotherapy for mantle cell
lymphoma: a 10-year single-centre experience with literature review.
AB - We retrospectively evaluated consecutive patients diagnosed with Mantle cell
lymphoma (MCL) between 01 January 2000 and 31 December 2009. Eighty eight
patients with MCL were included in the analysis of whom 46 (52%) received
abbreviated Hyper-CVAD (a total of two cycles; with addition of Rituximab since
2005) with an intention of proceeding to autologous hematopoietic cell
transplantation (auto-HCT), with a median age of 58 years. Response rate to
induction at auto-HCT time was 89% and complete response was 61%. Forty four
patients received an auto-HCT with a 5-year progression-free survival (PFS) and
overall survival (OS) were 31.2% and 62.5%, respectively. There were 42
nontransplant eligible patients with a median age of 72 years, and 5-year PFS and
OS were 0.0% and 39.9%, respectively. The median survival and PFS in the auto-HCT
eligible group were 68 and 33 months, compared to 32 and 12 months in
nontransplant eligible group, without a plateauing of the survival curves in
either group. Treatment-related mortality in the auto-HCT eligible group was
10.9% (n = 5); two patients died during R-Hyper-CVAD and 3 (6.8%) experienced
transplant-related mortality. An abbreviated R-Hyper-CVAD-based induction
strategy followed by consolidative auto-HCT is feasible and provides moderate
potential of long-term survival. Further research to define risk-adapted
strategies; to optimize disease control, is required.
PMID- 26432257
TI - Notch signaling induces cell proliferation in the labrum in a regulatory network
different from the thoracic legs.
AB - The insect head is composed of several segments and an anterior non-segmental
region. While patterning of the segmental region relies - at least in part - on
the known trunk patterning mechanisms, development of the anterior most region
remains poorly understood. The labrum is an enigmatic structure of the anterior
median region (AMR) of the insect head. Based on similar development and gene
expression patterns it has been suggested to be a serial homolog of trunk
appendages. However, its position in the non-segmental region indicated an
independent origin. In order to learn more about development of the AMR including
the labrum, we screened the results of the large scale RNAi screen iBeetle to
identify novel genes. We found the Notch ligand Tc-Serrate and the ubiquitin
ligase Tc-mind bomb1 to be required for labrum formation. Further studies showed
that Notch signaling is acting upstream of the genetic hierarchy and is required
for regulating cell proliferation. We combined our work with previous data to
compare the regulatory gene networks of labrum and trunk appendage formation.
This reveals that despite the involvement of a similar set of genes, the genetic
interactions are quite different.
PMID- 26432258
TI - Integrin beta4 regulation of PTHrP underlies its contribution to mammary gland
development.
AB - The integrin alpha6beta4 (referred to as beta4) is expressed in epithelial cells
where it functions as a laminin receptor. Although in vitro studies have
implicated beta4 in the biology of mammary epithelial cells, its contribution to
mammary gland development has not been settled. To address this problem, we
generated and analyzed itgb4(flox/flox)MMTV-Cre(-) and itgb4(flox/flox)MMTV
Cre(+) mice. The salient features of embryonic mammary tissue from
itgb4(flox/flox)MMTV-Cre(+) mice were significantly smaller mammary buds and
increased apoptosis in the surrounding mesenchyme. Also, compared to control
glands, the itgb4-deleted mammary buds lacked expression of the progenitor cell
marker CK14 and they were unable to generate mammary glands upon transplantation
into cleared fat pads of recipient mice. Analysis of mammary glands at puberty
and during pregnancy revealed that itgb4-diminished mammary tissue was unable to
elongate and undergo branching morphogenesis. Micro-dissection of epithelial
cells in the mammary bud and of the surrounding mesenchyme revealed that loss of
beta4 resulted in a significant decrease in the expression of parathyroid hormone
related protein (PTHrP) in epithelial cells and of target genes of the PTHrP
receptor in mesenchymal cells. Given that the phenotype of the itgb4-deleted
mammary tissue mimicked that of the PTHrP knockout, we hypothesized that beta4
contributes to mammary gland development by sustaining PTHrP expression and
enabling PTHrP signaling. Indeed, the inability of itgb4-deleted mammary buds to
elongate was rescued by exogenous PTHrP. These data implicate a critical role for
the beta4 integrin in mammary gland development and provide a mechanism for this
role.
PMID- 26432259
TI - Operative Factors Associated with the Development of New Brain Lesions During
Awake Carotid Endarterectomy.
AB - OBJECTIVES: The aim was to analyse a prospective, consecutive series of awake
carotid endarterectomy (CEA) patients undergoing, when possible, pre- and
postoperative diffusion-weighted magnetic resonance imaging brain scans (DWI).
METHODS: All CEA patients from June 23, 2006, to January 13, 2012, were
prospectively entered in the study. CEA was performed under regional cervical
block. Only patients demonstrating shunt dependence were shunted. Before August
7, 2008, all longitudinal endarterectomy had been performed with a vein patch.
From that date all CEA were eversions without a patch, except shunted patients
who were vein patched. DWI was performed 2 days before and 5 days after (3
Tesla). Scans were reported by MRI-trained radiologists. Logistic regression
analysis (LRA) identified predictive variables for MRI changes using backward
stepwise elimination of variables with p > .05. RESULTS: There was a total of 295
consecutive CEA. There were no deaths but four clinical strokes (1.4 %); 89
excluded from DWI leaving 206; of these 27 (13%) developed new DWI lesions
including four of 57 (7%) in the asymptomatic group and 23 of 149 (15%)
symptomatic patients. Nineteen of the 206 (9.2%) were shunted. LRA showed that
shunt dependence was highly associated with new DWI lesions: odds ratio (OR)
6.43; 95% confidence interval (CI) 2.3-17.9; p < .001. Both the vein patched, non
shunted group (OR .25; CI 0.09-0.72; p = .010) and the eversion (all non-shunted
and all non-patched) group (OR 0.05; CI 0.01-0.22; p < .001) were associated with
a low risk of new lesions, with the eversion group a lower risk than the patched
group. CONCLUSIONS: One in every eight CEA patients developed new DWI lesions
(rate doubled in symptomatic patients). Shunt dependence in conscious CEA
patients is highly associated with the development of new DWI lesions compared
with non-shunted patients. For non-shunted patients the new lesion risk is low,
and in those patients the risk in the eversion group is lower than in the patched
group.
PMID- 26432260
TI - Unfit for Repair After Screening for Abdominal Aortic Aneurysm: Do We Fail to
Fulfil the Basic WHO Criterion of an Available Treatment?
PMID- 26432261
TI - Sonic hedgehog-responsive lipoxygenases and cyclooxygenase-2 modulate Dectin-1
induced inflammatory cytokines.
AB - Immune responses during fungal infections are predominately mediated by 5/15
lipoxygenases (LO)- or cyclooxygenase (COX)-2-catalysed bioactive eicosanoid
metabolites like leukotrienes, lipoxins and prostaglandins. Although few host
mediators of fungi-triggered eicosanoid production have been established, the
molecular mechanism of expression and regulation of 5-LO, 15-LO and COX-2 are not
well-defined. Here, we demonstrate that, macrophages infected with representative
fungi Candida albicans, Aspergillus flavus or Aspergillus fumigatus or those
treated with Curdlan, a selective agonist of pattern recognition receptor for
fungi Dectin-1, displays increased expression of 5-LO, 15-LO and COX-2.
Interestingly, Dectin-1-responsive Syk pathway activates mTOR-sonic hedgehog
(SHH) signaling cascade to stimulate the expression of these lipid metabolizing
enzymes. Loss-of-function analysis of the identified intermediaries indicates
that while Syk-mTOR-SHH pathway-induced 5-LO and 15-LO suppressed the Dectin-1
responsive pro-inflammatory signature cytokines like TNF-alpha, IL-1beta and IL
12, Syk-mTOR-SHH-induced COX-2 positively regulated these cytokines. Dectin-1
stimulated IL-6, however, is dependent on 5-LO, 15-LO and COX-2 activity.
Together, the current study establishes Dectin-1-arbitrated host mediators that
direct the differential regulation of immune responses during fungal infections
and thus are potential candidates of therapeutic intervention.
PMID- 26432262
TI - Cytotoxicity and mutagenicity of sidestream cigarette smoke particulate matter of
different particle sizes.
AB - Sidestream cigarette smoke, the major component of environmental tobacco smoke,
is a complex and reactive aerosol. The particulate matter (PM) in sidestream
smoke is one of the carriers of chemical constituents. However, particle size
dependent toxicological effects of PM are poorly understood. In this study, we
evaluated the relationship between the PM size and in vitro cytotoxicity and
mutagenicity of sidestream cigarette smoke. A NanoMoudi-II(TM) 125A was used to
collect PM samples ranging from 10 nm to 10 MUm. The in vitro toxicity of PM was
evaluated using a neutral red cytotoxicity assay and Salmonella mutagenicity
assay. The results showed that the cytotoxicity and mutagenicity of PM larger
than 1 MUm was significantly lower than PM sized 10 nm-1 MUm. Furthermore, there
was a noticeable trend that the smaller the size of the PM of sidestream
cigarette smoke, the greater the toxicity. This study suggests that the toxicity
of PM in sidestream cigarette smoke is size-dependent.
PMID- 26432263
TI - Contributions of a compost-biochar mixture to the metal sorption capacity of a
mine tailing.
AB - One technique applied to restore degraded or contaminated soils is to use
amendments made of different types of waste materials, which in turn may contain
metals such as Cu, Pb and Zn. For this reason, it is important to determine the
capacity of the soil to retain these materials, and to compare the sorption
capacity between an amended soil and another unamended soil. The aim of this
study was to determine the mobility and availability of these metals in the soil
after applying the amendment, and how it affected the soil's sorption capacity.
Sorption isotherms were compared with the empirical models of Langmuir and
Freundlich to estimate the sorption capacity. The overall capacity of the soils
to sorb Cu, Pb or Zn was evaluated as the slope Kr. The amendments used in this
study were a mixture made of compost and biochar in different proportions (20,
40, 60, 100 %), which were applied to the mine tailing from a settling pond from
a copper mine. The mine tailing that were amended with the mixture of compost and
biochar had a higher sorption capacity than the mine tailing from the unamended
pond, and their sorption isotherms had a greater affinity towards Cu, Pb and Zn
than the mine tailing that was studied. Therefore, the results obtained show that
adding a mixture of compost and biochar favours the retention of Cu, Pb and Zn in
mine tailing.
PMID- 26432264
TI - Sources and potential health risk of gas phase PAHs in Hexi Corridor, Northwest
China.
AB - Gas phase polycyclic aromatic hydrocarbons (PAHs) in Hexi Corridor, Northwest
China were determined during heating and non-heating seasons, respectively, using
passive air samplers. Polyurethane foam (PUF) disks were chosen as the sampling
medium. Fifteen PAHs out of the 16 PAHs classified by the United States
Environmental Protection Agency (U.S. EPA) were detected in this field sampling
investigation. The atmospheric levels of sampled PAHs were higher at urban sites
than that at rural sites among 14 sampling sites and increased during heating
season. The highest concentration (11.34 ng m(-3)) was observed in Lanzhou during
the heating season, the capital and largest industrial city of Gansu Province.
PAH contamination in air was dominated by three aromatic ring congeners. Possible
sources of PAHs were apportioned using PAH species ratios and the principle
component analysis (PCA) combined with a multiple linear regression (MLR) method.
Fossil fuel consumption was identified to be the predominant source of PAHs over
Hexi Corridor, accounting for 43 % of the concentration of total (15) PAHs.
Backward and forward trajectory and cluster analysis were also carried out to
identify potential origins of PAHs monitored at several urban and rural sites.
Lung cancer risk of local residents to gas phase PAHs via inhalation exposure
throughout the province was found to be around a critical value of the lung
cancer risk level at 10(-6) recommended by the U.S. EPA risk assessment
guideline.
PMID- 26432265
TI - Effects of artemisinin sustained-release granules on mixed alga growth and
microcystins production and release.
AB - To safely and effectively apply artemisinin sustained-release granules to control
and prevent algal water-blooms, the effects of artemisinin and its sustained
release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and
Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of
microcystins (MCs) were studied. The results showed that artemisinin sustained
release granules inhibited the growth of M. aeruginosa (above 95% IR) and S.
obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin
sustained-release granules had a longer inhibition effect on growth of pure algae
and algal coexistence than direct artemisinin dosing. The artemisinin sustained
release granules could decrease the production and release of algal toxins due to
the continued stress of artemisinin released from artemisinin sustained-release
granules. There was no increase in the total amount of MC-LR in the algal cell
culture medium.
PMID- 26432266
TI - A comparative study with biologically and chemically synthesized nZVI:
applications in Cr (VI) removal and ecotoxicity assessment using indigenous
microorganisms from chromium-contaminated site.
AB - In the present communication, we report a comparative study of Cr (VI) removal
using biologically synthesized nano zero valent iron (BS-nZVI) and chemically
synthesized nZVI (CS-nZVI), both immobilized in calcium alginate beads. The
parameters like initial Cr (VI) concentration, nZVI concentration, and the
contact time for Cr (VI) removal were optimized based on Box-Behnken design (BBD)
by response surface modeling at a constant pH 7. Under the optimized conditions
(concentration of nZVI = 1000 mg L(-1), contact time = ~ 80 min, and initial
concentration of Cr (VI) = 10 mg L(-1)), the Cr (VI) removal by the immobilized
BS-nZVI and CS-nZVI alginate beads was 80.04 and 81.08 %, respectively. The
adsorption of Cr (VI) onto the surface of alginate beads was confirmed by
scanning electron microscopy with energy-dispersive x-ray spectroscopy (SEM-EDX),
Fourier transform infrared spectroscopy (FT-IR), and Brunauer-Emmett-Teller (BET)
analysis. The applicability of the process using both the sorbents was
successfully test medium Cr (VI) spiked environmental water samples. In order to
assess the ecotoxic effects of nZVI, the decline in cell viability, generation of
intracellular reactive oxygen species (ROS), cell membrane damage, and biouptake
was studied at 1000 mg L(-1) concentration, with five indigenous bacterial
isolates from chromium-contaminated lake sediments and their consortium.
PMID- 26432267
TI - Characteristics of simultaneous ammonium and phosphate adsorption from hydrolysis
urine onto natural loess.
AB - Nutrient recovery from human urine is a promising pretreatment of domestic
wastewater and provides a sustainable recyclability of N and P. In this study,
batch experiments were conducted to identify the characteristics of natural loess
(NL) for the adsorption and recovery of ammonium and phosphate from hydrolysis
urine (HU). The adsorption mechanisms, the adsorption kinetics and isotherms, as
well as the major influencing factors, such as pH and temperature, were
investigated. Results revealed that adsorption of ammonium occurred by means of
ion exchange and molecule adsorption with the = Si-OH groups, while phosphate
adsorption was based on the calcium phosphate precipitation reaction and
formation of inner-sphere complexes with = M-OH groups. The adsorption processes
of ammonium and phosphate were well described by the pseudo-second-order kinetic
model and the Freundlich isotherm model. Adsorption of phosphate was endothermic,
while ammonium adsorption was exothermic. Furthermore, the maximum ammonium and
phosphate adsorption capacities of NL was 23.24 mg N g(-1) and 4.01 mg P g(-1) at
an initial pH of 9 and 10, respectively. Results demonstrated that nutrient
adsorbed NL used as compound fertilizer or conventional fertilizer superaddition
was feasible for its high contents of N and P as well as its environmental
friendliness.
PMID- 26432245
TI - A global reference for human genetic variation.
AB - The 1000 Genomes Project set out to provide a comprehensive description of common
human genetic variation by applying whole-genome sequencing to a diverse set of
individuals from multiple populations. Here we report completion of the project,
having reconstructed the genomes of 2,504 individuals from 26 populations using a
combination of low-coverage whole-genome sequencing, deep exome sequencing, and
dense microarray genotyping. We characterized a broad spectrum of genetic
variation, in total over 88 million variants (84.7 million single nucleotide
polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000
structural variants), all phased onto high-quality haplotypes. This resource
includes >99% of SNP variants with a frequency of >1% for a variety of
ancestries. We describe the distribution of genetic variation across the global
sample, and discuss the implications for common disease studies.
PMID- 26432269
TI - The use of food wastes as feed ingredients for culturing grass carp
(Ctenopharyngodon idellus) in Hong Kong.
AB - Different types of food wastes, e.g., meats, bones, cereals, fruits, and
vegetables, were collected from hotels in Hong Kong, mixed in different ratio,
and processed into feed pellets (food wastes (FWs) A, B, and C) for feeding
trials in aquaculture species. Grass carp fed with cereal-dominant feed (FW A)
showed the best growth (in terms of specific growth rate, relative weight gain,
and protein efficiency ratio), among all food waste feeds. However, the growth
rates of food waste groups especially the meat product-contained feeds (FW B and
FW C) were lower than the commercial feed, Jinfeng((r)) 613 formulation
(control). The results indicated that grass carp utilized plant proteins better
than animal proteins and preferred carbohydrate as a major energy source than
lipid. The high-lipid content in feed containing meat products was also a
possible reason for hindering growth and resulted high body lipid. It is
suggested that lipid should be removed in the preparation of food waste feed or
further investigations by implementing supplements, e.g., enzymes in feed to
enhance lipid or protein utilization by fish. This utilization of food waste
could be an effective and practical way to deal with these wastes in this densely
populated city.
PMID- 26432268
TI - Comparative study of diethyl phthalate degradation by UV/H2O2 and UV/TiO2:
kinetics, mechanism, and effects of operational parameters.
AB - The photodegradation of diethyl phthalate (DEP) by UV/H2O2 and UV/TiO2 is
studied. The DEP degradation kinetics and multiple crucial factors effecting the
clearance of DEP are investigated, including initial DEP concentration ([DEP]0),
initial pH values (pH0), UV light intensity, anions (Cl(-), NO(3-), SO4 (2-),
HCO3 (-), and CO3 (2-)), cations (Mg(2+), Ca(2+), Mn(2+), and Fe(3+)), and humic
acid (HA). Total organic carbon (TOC) removal is tested by two treatments. And,
cytotoxicity evolution of DEP degradation intermediates is detected. The
relationship between molar ratio ([H2O2]/[DEP] or [TiO2]/[DEP]) and degradation
kinetic constant (K) is also studied. And, the cytotoxicity tests of DEP and its
degradation intermediates in UV/H2O2 and UV/TiO2 treatments are researched. The
DEP removal efficiency of UV/H2O2 treatment is higher than UV/TiO2 treatment. The
DEP degradation fitted a pseudo-first-order kinetic pattern under experimental
conditions. The K linearly related with molar ratio in UV/H2O2 treatment while
nature exponential relationship is observed in the case of UV/TiO2. However, K
fitted corresponding trends better in H2O2 treatment than in TiO2 treatment. The
Cl(-) is in favor of the DEP degradation in UV/H2O2 treatment; in contrast, it is
disadvantageous to the DEP degradation in UV/TiO2 treatment. Other anions are all
disadvantageous to the DEP degradation in two treatments. Fe(3+) promotes the
degradation rates significantly. And, all other cations in question inhibit the
degradation of DEP. HA hinders DEP degradation in two treatments. The
intermediates of DEP degradation in UV/TiO2 treatment are less toxic to
biological cell than that in UV/H2O2 treatment.
PMID- 26432271
TI - Chemical element accumulation in tree bark grown in volcanic soils of Cape Verde
a first biomonitoring of Fogo Island.
AB - Barks from Prosopis juliflora (acacia) were collected in 12 sites of different
geological contexts over the volcanic Fogo Island (Cape Verde). Elemental
contents of Ba, Br, Co, Cr, Fe, K, Na, Zn and some rare earth elements (REE)-La,
Ce, Sm, Eu, Tb, Yb, and Lu, were obtained for biological samples and topsoils by
using k 0-standardized and comparative method of instrumental neutron activation
analysis (INAA), aiming the evaluation of chemical elements uptake by acacia
bark. This first biomonitoring study of Fogo Island showed that, in general,
significant accumulations of trace elements present in high amounts in these
soils occur. This can be partially explained by the semi-arid climate with a
consequent bioavailability of chemical elements when rain drops fall in this non
polluted environment. REE enrichment factors (EFs) increase with the decrease of
ionic radius. Heavy REE (HREE) are significantly enriched in bark, which agrees
with their release after the primary minerals breakdown and the formation of more
soluble compounds than the other REE, and uptake by plants. Among the potential
harmful chemical elements, Cr appears to be partially retained in nanoparticles
of iron oxides. The high EFs found in tree barks of Fogo Island are certainly of
geogenic origin rather than anthropogenic input since industry and the use of
fertilizers is scarce.
PMID- 26432270
TI - Lead toxicity in rice: effects, mechanisms, and mitigation strategies--a mini
review.
AB - Lead (Pb) is a major environmental pollutant that affects plant morpho
physiological and biochemical attributes. Its higher levels in the environment
are not only toxic to human beings but also harmful for plants and soil microbes.
We have reviewed the uptake, translocation, and accumulation mechanisms of Pb and
its toxic effects on germination, growth, yield, nutrient relation,
photosynthesis, respiration, oxidative damage, and antioxidant defense system of
rice. Lead toxicity hampers rice germination, root/shoot length, growth, and
final yield. It reduces nutrient uptake through roots, disrupts chloroplastic
ultrastructure and cell membrane permeability, induces alterations in leaves
respiratory activities, produces reactive oxygen species (ROS), and triggers some
enzyme and non-enzymatic antioxidants (as defense to oxidative damage). In the
end, biochar amendments and phytoremediation technologies have been proposed as
soil remediation approaches for Pb tainted soils.
PMID- 26432272
TI - Supplemental exogenous NPK application alters biochemical processes to improve
yield and drought tolerance in wheat (Triticum aestivum L.).
AB - The recent food security issues, combined with the threats from climate change,
demand future farming systems to be more precise and accurate to fulfill the ever
increasing global food requirements. The role of nutrients such as nitrogen (N),
phosphorous (P), and potassium (K) in stimulating plant growth and development is
well established; however, little is known about their function, if applied in
combination, in improving crop yields under environmental stresses like drought.
The aim of this study was to evaluate the effects of combined foliar spray of
supplemental NPK (NPKc) on physiological and biochemical mechanisms that enhance
the drought tolerance potential of wheat for improved yield. Foliar NPKc markedly
influenced the accumulation of osmoprotectants and activity of both nitrogen
assimilation and antioxidant enzymes. It significantly improved the concentration
of proline (66 %), total soluble sugars (37 %), and total soluble proteins (10 %)
and enhanced the activity of nitrate reductase, nitrite reductase, catalase, and
peroxidase by 47, 45, 19, and 8 %, respectively, with respect to no spray under
water-deficit conditions which, in turn, improve the yield and yield components.
The accumulation of osmolytes and activity of antioxidant machinery were more
pronounced in drought tolerant (Bhakkar-02) than sensitive genotype (Shafaq-06).
PMID- 26432273
TI - Surface microstructural features of scales in relation to toxic stress of Basic
Violet-1.
AB - The present work deals with scanning electron microscopic (SEM) studies of the
scales of Labeo rohita on exposure to lethal and sublethal doses of Basic Violet
1 (an important textile and hair colorant). The dye induced loosening of the
scales and caused breakage and disorganization of lepidonts. Erosion of lepidonts
occurred mostly in the fish exposed to 0.20 and 0.40 mg/L dye, during acute
exposure and to 0.0225 and 0.045 mg/L dye, during the subchronic exposure.
However, lepidonts were sloughed off from their sockets in 0.60 and 0.80 mg/L dye
during acute exposure and in 0.09 mg/L dye during the subchronic exposure.
Circuli, the base that provides anchorage to the lepidonts, got damaged, and
tubercles responsible for coloration of a fish became atrophied with an increase
in the duration of exposure. The results of the present investigation clearly
indicated that exposure to Basic Violet-1 (BV-1) even at a concentration as low
as 0.0225 mg was responsible for deleterious changes in the scale morphology of
the test fish after 150 days of exposure. Similar changes were observed in the
scales of the dead fish also. It can thus be suggested that this noninvasive
technique is very helpful for evaluating the health status of an aquatic body. At
the same time, the changes in ultramorphology of scales can act as an early
indicator of the stress of very minute doses of dyes and even the scales of a
dead fish can act as indicators of the untoward changes that would have occurred
in the environment of the fish before death.
PMID- 26432274
TI - The saga of the duration of dual antiplatelet therapy after drug-eluting stent
placement.
PMID- 26432275
TI - Echocardiographic measurement of left atrial volume: Does the method matter?
AB - BACKGROUND: Four two-dimensional echocardiographic methods (cube, ellipsoid,
Simpson's and area-length) can be used to assess left atrial volume (LAV). AIMS:
To compare absolute LAV measurements and evaluate agreement regarding the
semiquantitative assessment of degree of left atrial (LA) enlargement, between
methods. METHODS: We prospectively measured LAV in 51 healthy volunteers using
the four methods, and defined thresholds for moderate (mean+2 standard deviations
[SDs]) and severe (mean+4 SDs) LA enlargement for each method. In 372 patients
referred for echocardiography, we compared absolute LAV measurements and
agreement between methods. RESULTS: LAV was significantly different between
methods in the healthy volunteer group (11 +/- 4, 17 +/- 3, 26 +/- 6 and 28 +/- 7
mL/m(2), respectively; P<0.0001), resulting in different thresholds for moderate
and severe LA enlargement. LAV was also significantly different in the 372
patients (30 +/- 20, 47 +/- 27, 61 +/- 34 and 65 +/- 36 mL/m(2), respectively;
P<0.0001). Agreement regarding degree of LA enlargement (none, moderate, severe),
using the area-length method as reference, was modest with the cube method
(kappa=0.41), correct with the ellipsoid method (kappa=0.60) and excellent with
Simpson's method (kappa=0.83). CONCLUSION: The choice of the method had a major
effect on assessment of degree of LA enlargement. Our results suggest that the
cube and ellipsoid methods, which significantly underestimated LAV and provided
modest agreement, should be disregarded. In contrast, Simpson's method and the
area-length method were slightly different, but showed close agreement, and
should be preferred, using dedicated thresholds (50 and 56 mL/m(2) respectively).
PMID- 26432276
TI - Effect of the aqueous extract of the aerial parts of Monsonia angustifolia E.
Mey. Ex A. Rich., on the sexual behaviour of male Wistar rats.
AB - BACKGROUND: Monsonia angustifolia (Geraniaceae) is a medicinal plant
traditionally used in South Africa to increase libido and to treat erectile
dysfunction. METHODS: In-vivo aphrodisiac activities of the crude extracts of the
plant prepared in water at 3, 30 and 300 mg/kg body weight were evaluated for 7
days using sildenafil citrate (Viagra) and 1% ethanol in distilled water as
positive and negative controls respectively. Male rats were selected and
monitored in each group for sexual behaviour by exposing them to sexually
receptive females on days 1, 3 and 7 for 60 minutes each between 7:00 pm and 3:00
am. The following male sexual parameters were observed: Mount Frequency (MF),
Intromission Frequency (IF), Mount Latency (ML), Intromission Latency (IL),
Ejaculation Frequency (EF), Ejaculatory Latency (EL) and Post-Ejaculatory
Interval (PEI). RESULTS: The administration of the extract resulted in
significant increase (p < 0.05) in mount frequency, intromission frequency,
ejaculation frequency, ejaculation latency and serum hormone concentrations. The
computed indices of sexual behaviour such as erection, quick flips, long flips
and total penile reflexes were also increased. However, the mount latency,
intromission latency and post ejaculation interval were significantly decreased
throughout the experimental period. The administration of 300 mg/kg body weight
of the aqueous extract produced the best effects in all the parameters.
CONCLUSION: Generally, the extract of Monsonia angustifolia produced pro-sexual
stimulatory effects in the male rats especially when administered at 300 mg/kg
body weight. The results validate the use of the plant by the indigenous people
to increase libido and treat premature ejaculation and erectile dysfunction in
males.
PMID- 26432277
TI - How Distractor Objects Trigger Referential Overspecification: Testing the Effects
of Visual Clutter and Distractor Distance.
AB - In two experiments, we investigate to what extent various visual saliency cues in
realistic visual scenes cause speakers to overspecify their definite object
descriptions with a redundant color attribute. The results of the first
experiment demonstrate that speakers are more likely to redundantly mention color
when visual clutter is present in a scene as compared to when this is not the
case. In the second experiment, we found that distractor type and distractor
color affect redundant color use: Speakers are most likely to overspecify if
there is at least one distractor object present that has the same type, but a
different color than the target referent. Reliable effects of distractor distance
were not found. Taken together, our results suggest that certain visual saliency
cues guide speakers in determining which objects in a visual scene are relevant
distractors, and which not. We argue that this is problematic for algorithms that
aim to generate human-like descriptions of objects (such as the Incremental
Algorithm), since these generally select properties that help to distinguish a
target from all objects that are present in a scene.
PMID- 26432278
TI - Why do women invest in pre-pregnancy health and care? A qualitative investigation
with women attending maternity services.
AB - BACKGROUND: Despite the importance attributed to good pre-pregnancy care and its
potential to improve pregnancy and child health outcomes, relatively little is
known about why women invest in pre-pregnancy health and care. We sought to gain
insight into why women invested in pre-pregnancy health and care. METHODS: We
carried out 20 qualitative in-depth interviews with pregnant or recently pregnant
women who were drawn from a survey of antenatal clinic attendees in London, UK.
Interviewees were purposively sampled to include high and low investors in pre
pregnancy health and care, with variation in age, partnership status, ethnicity
and pre-existing medical conditions. Data analysis was conducted using the
Framework method. RESULTS: We identified three groups in relation to pre
pregnancy health and care: 1) The "prepared" group, who had high levels of
pregnancy planning and mostly positive attitudes to micronutrient supplementation
outside of pregnancy, carried out pre-pregnancy activities such as taking folic
acid and making changes to diet and lifestyle. 2) The "poor knowledge" group, who
also had high levels of pregnancy planning, did not carry out pre-pregnancy
activities and described themselves as having poor knowledge. Elsewhere in their
interviews they expressed a strong dislike of micronutrient supplementation. 3)
The "absent pre-pregnancy period" group, had the lowest levels of pregnancy
planning and also expressed anti-supplement views. Even discussing the pre
pregnancy period with this group was difficult as responses to questions quickly
shifted to focus on pregnancy itself. Knowledge of folic acid was poor in all
groups. CONCLUSION: Different pre-pregnancy care approaches are likely to be
needed for each of the groups. Among the "prepared" group, who were proactive and
receptive to health messages, greater availability of information and better
response from health professionals could improve the range of pre-pregnancy
activities carried out. Among the "poor knowledge" group, better response from
health professionals might yield greater uptake of pre-pregnancy information. A
different, general health strategy might be more appropriate for the "absent pre
pregnancy period" group. The fact that general attitudes to micronutrient
supplementation were closely related to whether or not women invested in pre
pregnancy health and care was an unanticipated finding and warrants further
investigation.
PMID- 26432279
TI - Invasive Vespula Wasps Utilize Kairomones to Exploit Honeydew Produced by Sooty
Scale Insects, Ultracoelostoma.
AB - Vespula wasps are widely distributed invasive alien species that are able to
reach high population densities in the 1.2 M ha of beech forests (Fuscospora
spp.) of New Zealand's South Island. These endemic temperate forests have an
abundance of carbohydrate-rich honeydew produced by native scale insects
(Ultracoelostoma spp.). A characteristic aroma is associated with the honeydew in
beech forests, which we hypothesized is the signal used by wasps to harvest the
vast resources previously exploited by birds and other insects. Volatile
collections were taken of black beech tree trunks with honeydew and sooty mold
present, and analyzed with a gas chromatograph-mass spectrometer. Eleven
compounds (benzaldehyde, benzyl alcohol, 2-phenylethyl acetate, 2-phenylethanol,
phenylacetaldehyde, methyl 2-phenylacetate, ethyl 2-phenylacetate, methyl
salicylate, n-octanol, octan-3-ol, and 1-octen-3-ol) were positively identified
from the headspace, and were shown to elicit an electrophysiological response
from Vespula vulgaris worker antennae by using electroantennography (EAG). Field
trials with delta traps individually baited with these compounds confirmed wasp
attraction to 8 of the 11 compounds tested, with 2-phenylethyl acetate, methyl
salicylate, and octan-3-ol capturing the same numbers of wasps as the control. In
later trials, attraction to a 1:1 blend of benzaldehyde and n-octanol was
significantly higher (45%) than to any other treatment. Many of the chemicals
identified are known to be associated with fermenting sugars, or with fungal
aroma. Benzaldehyde and n-octanol are common compounds produced by many different
species in nature. The ability to respond to generic signals emanating from sugar
resources is likely to contribute to the success of V. vulgaris as an invasive
species.
PMID- 26432280
TI - Growth factors and experimental arterial grafts.
AB - BACKGROUND: The production of growth factors from several experimental arterial
conduits was determined. METHODS: We implanted 105 experimental arterial grafts
that were 1 cm long in the abdominal aorta of Lewis rats (average weight, 250 g).
Five different types of grafts were analyzed: arterial isografts, vein grafts,
arterial allografts, and polytetrafluoroethylene (PTFE) grafts with normal or
decreased compliance. Animals were killed humanely 4 weeks after surgery and the
production of platelet-derived growth factor (PDGF), basic fibroblast growth
factor (bFGF), transforming growth factor-beta, tumor necrosis factor-alpha, and
interleukin-1 was analyzed. RESULTS: Myointimal hyperplasia (MH) was evident in
vein grafts, arterial allografts, and PTFE grafts, but not in arterial isografts.
Growth factor production was increased for grafts prone to develop MH like vein,
PTFE grafts, and arterial allografts. PDGF and bFGF were increased significantly
for PTFE and vein grafts, but not for arterial allografts. The importance of bFGF
and PGDF was confirmed by the capability of antibody to PDGF and to bFGF to
reduce the mitogenic activity of smooth muscle cells, in vivo and in vitro, for
PTFE and vein grafts, but not for arterial allografts, in which a predominant
role was played by interleukin-1 and tumor necrosis factor-alpha. CONCLUSIONS:
Agents able to neutralize this increased production of growth factors, either
directly or by competition with their receptors, can prevent MH formation.
PMID- 26432281
TI - Physician specialty and variation in carotid revascularization technique selected
for Medicare patients.
AB - OBJECTIVE: Carotid artery stenting (CAS) has become an alternative to carotid
endarterectomy (CEA) for select patients with carotid atherosclerosis. We
hypothesized that the choice of CAS vs CEA varies as a function of treating
physician specialty, which would result in regional variation in the relative use
of these treatment types. METHODS: We used Medicare claims (2002-2010) to
calculate annual rates of CAS and CEA and examined changes by procedure type over
time. To assess regional preferences surrounding CAS, we calculated the
proportion of revascularizations by CAS, across hospital referral regions,
defined according to the Dartmouth Atlas of Healthcare. We then examined
relationships between patient factors, physician specialty, and regional use of
CAS. RESULTS: The annual number of all carotid revascularization procedures
decreased by 30% from 2002 to 2010 (3.2 to 2.3 per 1000; P = .005). Whereas rates
of CEA declined by 35% during these 8 years (3.0 to 1.9 per 1000; P < .001), CAS
utilization increased by 5% during the same interval (0.30 to 0.32 per 1000; P =
.014). Variation in utilization of carotid revascularization varied across the
Unites States, with some regions performing as few as 0.7 carotid procedure per
1000 beneficiaries (Honolulu, Hawaii) and others performing nearly 8 times as
many (5.3 per 1000 in Houma, La). Variation in procedure type (CEA vs CAS) was
evident as well, as the proportion of carotid revascularization procedures that
were constituted by CAS varied from 0% (Casper, Wyo, and Meridian, Miss) to 53%
(Bend, Ore). The majority of CAS procedures were performed by cardiologists (49%
of all CAS cases), who doubled their rates of CAS during the study period from
0.07 per 1000 in 2002 to 0.15 per 1000 in 2010. CONCLUSIONS: Variation in rates
of carotid revascularization exists. Whereas rates of carotid revascularization
have declined by more than 30% in recent years, utilization of CAS has increased.
The proportion of all carotid revascularization procedures performed as CAS
varies markedly by geographic region, and regions with the highest proportion of
cardiologists perform the most CAS procedures. Evidence-based guidelines for
carotid revascularization will require a multidisciplinary approach to ensure
uniform adoption across specialties that care for patients with carotid artery
disease.
PMID- 26432282
TI - Predicting outcomes for infrapopliteal limb-threatening ischemia using the
Society for Vascular Surgery Vascular Quality Initiative.
AB - OBJECTIVE: The outcomes of open surgical or endovascular intervention for limb
threatening ischemia (LTI) involving the infrapopliteal vessels are dependent on
complex anatomic, demographic, and disease factors. To assist in decision-making,
we used the Vascular Quality Initiative (VQI) to derive a model using only
preoperatively available factors to predict important outcomes for open or
endovascular revascularization. METHODS: National VQI data for the infrainguinal
bypass and peripheral vascular intervention (PVI) modules were reviewed in a
blinded fashion for patients who underwent intervention for LTI of the
infrapopliteal vessels. Primary outcomes consisted of major adverse limb event
(MALE) and amputation-free survival (AFS). Generalized linear modeling was used
for the multivariate analyses, with entry of variables dependent on results of
univariate analysis. RESULTS: From January 2003 through August 2014 a total of
19,053 infrainguinal open bypass and 48,739 PVI procedures were identified, among
which 5264 and 5252, respectively, represented infrapopliteal (tibial-peroneal
pedal) revascularization for LTI. From these, 3036 infrapopliteal open bypass
patients and 1319 infrapopliteal PVI patients had sufficient follow-up data for
study inclusion. For open surgery, the reduced generalized linear model revealed
that American Society of Anesthesiologists class 4 or 5, previous major
amputation, living at home, and female sex had the greatest adverse effect on
MALE, and dialysis dependence, low body mass index, and lack of great saphenous
vein as a conduit had the greatest negative effect on AFS. For PVI, lesion length
from 10 to 15 cm, treatment of three or more arteries, and classification other
than A on the Trans-Atlantic Inter-Society Consensus demonstrated the largest
adverse effects on MALE, and dialysis dependence, low body mass index, and
congestive heart failure most negatively affected AFS. CONCLUSIONS: This study on
a cross-section of patients selected for intervention in academic and community
hospitals offers a "real world" glimpse of factors predictive of outcome. The VQI
can be used to derive models that predict the outcomes of open surgical bypass or
PVI for LTI involving the infrapopliteal vessels.
PMID- 26432283
TI - Staged hybrid repair of extensive thoracoabdominal aortic aneurysms secondary to
chronic aortic dissection.
AB - OBJECTIVE: Many patients with aortic dissection develop Crawford extent I or II
thoracoabdominal aortic aneurysms (TAAA). Because open repair is associated with
a high morbidity and mortality, hybrid approaches to TAAA repair are emerging. In
this study, we evaluated the midterm outcomes and aortic remodeling of a hybrid
technique that combines proximal thoracic endovascular aneurysm repair (TEVAR),
followed by staged distal open thoracoabdominal repair for patients with Crawford
extent I or II TAAAs secondary to chronic aortic dissection. METHODS: We
identified 19 patients with Crawford extent I (n = 1) or extent II (n = 18) TAAAs
secondary to chronic aortic dissection who underwent a staged hybrid repair from
2007 to 2014 at our institution. Nine patients had previous open ascending aortic
surgery for type I aortic dissection. Stage 1 TEVAR was performed via
percutaneous (n = 8), femoral cutdown (n = 8), or iliac exposure (n = 3). The
left subclavian artery was covered in nine patients and revascularized in eight
patients using carotid-subclavian bypass (n = 7) or laser fenestration (n = 1).
Stage 2 open repair was performed a median of 18 weeks later with partial
cardiopulmonary bypass via left femoral arterial and venous cannulation for
visceral and lower body perfusion. The open thoracoabdominal graft was
anastomosed proximally in an end to end fashion with the endograft. We then
assessed surgical morbidity and mortality, midterm survival, and freedom from
reintervention. Aortic remodeling was measured and change in maximum aortic and
false lumen diameter at last follow-up (median, 3 years) from baseline was
assessed. RESULTS: There were no deaths, strokes, or chronic renal failure in
this cohort. After stage 1 TEVAR, three patients required repeat intervention for
endoleak (type Ia, n = 1; type Ib, n = 1; type II, n = 1) before open repair.
After stage 2 open repair, there was a single delayed permanent paralysis 2 weeks
after discharge. At a median 3-year follow-up (range, 6 months-6.2 years), there
were no deaths, neurologic events, endoleaks, or TAAA reinterventions. Complete
false lumen thrombosis occurred in 100% of the patients, with maximum false lumen
diameter decreasing from 34.3 +/- 15.3 mm to 13.2 +/- 12.0 mm (P < .01) and total
aortic diameter decreasing from 60.2 +/- 9.0 mm to 49.4 +/- 9.6 mm (P < .01).
CONCLUSIONS: Staged hybrid TAAA repair, using a combination of proximal TEVAR
with open distal repair, can be performed using established endovascular skills
and technology coupled with traditional open aortic surgical techniques, with low
surgical morbidity and mortality. In the midterm, staged hybrid TAAA repair was
associated favorable survival, aortic remodeling, and freedom from
reintervention.
PMID- 26432284
TI - A ruptured abdominal aortic aneurysm that requires preoperative cardiopulmonary
resuscitation is not necessarily lethal.
AB - OBJECTIVE: A ruptured abdominal aortic aneurysm (RAAA) is associated with a high
mortality rate. If cardiopulmonary resuscitation (CPR) is required before
surgical repair, mortality rates are said to approach 100%. The aim of this
multicenter, retrospective study was to study outcome in RAAA patients who
required CPR before a surgical (endovascular or open) repair (CPR group). RAAA
patients who did not need CPR served as controls (non-CPR group). METHODS: Over a
5-year time period, demographic and clinical characteristics and specifics of
preoperative CPR if necessary were studied in all patients who were treated for a
RAAA in three large, nonacademic hospitals. RESULTS: A total of 199 consecutive
RAAA patients were available for analysis; 176 patients were surgically treated.
Thirteen of these 176 patients (7.4%) needed CPR, and 163 (92.6%) did not. A
38.5% (5 of 13) survival rate was observed in the CPR group. Thirty-day mortality
was almost three times greater in the CPR group compared with the non-CPR group
(61.5% vs 22.7%; P = .005). Both CPR patients who received endovascular aortic
repair survived. In contrast, survival in 11 CPR patients who underwent open RAAA
repair was 27% (3 of 11; P = .128). A trend for higher Hardman index was found in
patients who received CPR compared with patients who did not receive CPR (P =
.052). The 30-day mortality in patients with a 0, 1, 2, or 3 Hardman index was
16.1%, 31.0%, 37.9%, and 33.3%, respectively (P = .093). CONCLUSIONS: An RAAA
that requires preoperative CPR is not necessarily a lethal combination. Patient
selection must be tailored before surgery is denied.
PMID- 26432285
TI - Outcomes of endovascular aneurysm repair with contemporary volume-dependent sac
embolization in patients at risk for type II endoleak.
AB - OBJECTIVE: The aim of this study was to evaluate outcomes of intraoperative
aneurysm sac embolization during endovascular aneurysm repair (EVAR) in patients
considered at risk for type II endoleak (EII), using a sac volume-dependent dose
of fibrin glue and coils. METHODS: Between January 2012 and December 2014, 126
patients underwent EVAR. Based on preoperative computed tomography evaluation of
anatomic criteria, 107 patients (85%) were defined as at risk for EII and
assigned to randomization for standard EVAR (group A; n = 55, 44%) or EVAR with
intraoperative sac embolization (group B; n = 52, 42%); the remaining 19 patients
(15%) were defined as at low risk for EII and excluded from the randomization
(group C). Computed tomography scans were evaluated with OsiriX Pro 4.0 software
to obtain aneurysm sac volume. Freedom from EII, freedom from EII-related
reintervention, and aneurysm sac volume shrinkage at 6, 12, and 24 months were
compared by Kaplan-Meier estimates. Patients in group C underwent the same follow
up protocol as groups A and B. RESULTS: Patient characteristics, Society for
Vascular Surgery comorbidity scores (0.99 +/- 0.50 vs 0.95 +/- 0.55; P = .70),
and operative time (149 +/- 50 minutes vs 157 +/- 39 minutes; P = .63) were
similar for groups A and B. Freedom from EII was significantly lower for group A
compared with group B at 3 months (58% vs 80%; P = .002), 6 months (68% vs 85%; P
= .04), and 12 months (70% vs 87%; P = .04) but not statistically significant at
24 months (85% vs 87%; P = .57). Freedom from EII-related reintervention at 24
months was significantly lower for group A compared with group B (82% vs 96%; P =
.04). Patients in group B showed a significantly overall mean difference in
aneurysm sac volume shrinkage compared with group A at 6 months (-11 +/- 17 cm(3)
vs -2 +/- 14 cm(3); P < .01), 12 months (-18 +/- 26 cm(3) vs -3 +/- 32 cm(3); P =
.02), and 24 months (-27 +/- 25 cm(3) vs -5 +/- 26 cm(3); P < .01). Patients in
group C had the lowest EII rate compared with groups A and B (6 months, 5%; 12
months, 6%; 24 months, 0%) and no EII-related reintervention. CONCLUSIONS: This
randomized study confirms that sac embolization during EVAR, using a sac volume
dependent dose of fibrin glue and coils, is a valid method to significantly
reduce EII and its complications during early and midterm follow-up in patients
considered at risk. Although further confirmatory studies are needed, the faster
aneurysm sac volume shrinkage over time in patients who underwent embolization
compared with standard EVAR may be a positive aspect influencing the lower EII
rate also during long-term follow-up.
PMID- 26432286
TI - A technique for developing CAD geometry of long bones using clinical CT data.
AB - Computed tomography scans are a valuable tool for developing computational models
of bones. The objective of this study is to present a method to generate CAD
representations of long bones from clinically based CT scans. A secondary aim is
to apply the method to six long bones from a sample of three individuals.
Periosteal and endosteal bone surfaces were segmented and used to calculate the
characteristic cortical thickness, Tc, at 1 mm increments along the bone axis. In
the epiphyses where the value of Tc fell below the scanner threshold, the
endosteal bone layer was replaced using literature values projected inward from
the periosteal surface. On average, 74.7 +/- 7.4% of the bone geometry was above
the scanner cut-off and was therefore derived from the CT scan data. The
thickness measurement was also compared to experimental measurements of cadaveric
bone and was found to predict Tc with an error of 3.1%. This method presents a
possible solution for the characterization of characteristic thickness along the
length of the bone and may also aid in the development of orthopedic implant
design and subject specific finite element models.
PMID- 26432287
TI - Oligomerization between BSU1 Family Members Potentiates Brassinosteroid Signaling
in Arabidopsis.
PMID- 26432288
TI - Earlier diagnosis of neurodevelopmental disability can only help infants in
neonatal intensive care units.
PMID- 26432289
TI - No crucial amino acid changes in the predicted histo blood group antigen-binding
sites of norovirus genotype GII.4 capsid between non-secretors and secretors
origin might suggest an alternative route of infection or existence of
coincidental molecules.
PMID- 26432290
TI - TGF-beta induces miR-30d down-regulation and podocyte injury through Smad2/3 and
HDAC3-associated transcriptional repression.
AB - The microRNA-30 family plays important roles in maintaining kidney homeostasis.
Patients with focal segmental glomerulosclerosis (FSGS) have reduced miR-30
levels in glomerulus. TGF-beta represses miR-30s in kidney podocytes, which leads
to cytoskeleton damage and podocyte apoptosis. In this study, we investigated the
mechanism by which TGF-beta represses miR-30d in vitro. The human miR-30d
promoter contains multiple copies of Smad binding element-like sequences. A
fragment of 150 base pairs close to the transcription start site was negatively
regulated by TGF-beta to a similar extent as the 1.8 kb promoter, which was
blocked by histone-deacetylase inhibition. TGF-beta specifically enhanced HDAC3
expression. Knockdown of HDAC3 by shRNA or a selective inhibitor RGFP966
significantly relieved the repression of miR-30d mRNA and the promoter
transcription. TGF-beta promoted HDAC3 association with Smad2/3 and NCoR and
caused their accumulation at the putative Smad binding site on the miR-30d
promoter, which was prohibited by TSA or RGFP966. Furthermore, TSA or RGFP966
treatment reversed TGF-beta-induced up-regulation of miR-30d targets Notch1 and
p53 and alleviated the podocyte cytoskeleton damage and apoptosis. Taken
together, these findings pinpoint that TGF-beta represses miR-30d through a
Smad2/3-HDAC3-NCoR repression complex and provide novel insights into a potential
target for the treatment of podocyte injury-associated glomerulopathies. Key
message: MiR-30d promoter is negatively regulated by TGF-beta. TGF-beta down
regulates miR-30 through Smad signaling pathway. HDAC3 and NCoR are recruited by
Smad2/3 to mediate miR-30d repression by TGF-beta. HDAC3 acts as a critical
player in TGF-beta-induced miR-30d repression and podocyte injuries.
PMID- 26432291
TI - RNA Interference of Odorant-Binding Protein 2 (OBP2) of the Cotton Aphid, Aphis
gossypii (Glover), Resulted in Altered Electrophysiological Responses.
AB - Aphis gossypii (Glover) (Hemiptera: Aphididae) is a highly invasive pest that
feeds primarily on phloem resulting in severe economic loss to growers. A.
gossypii has cosmopolitan distribution with broad host range, polyphenism,
parthenogenetic mode of reproduction, vectoring abilities, and host alteration
which has profound influence on its management. Odorant-binding proteins (OBPs)
in insects are involved in olfaction, playing a key role in orienting the insect
for feeding or oviposition. Recent studies revealed that OBP2 is found in both
sensilla trichodea and sensilla basiconica and is preferentially binds to plant
volatiles, thus playing crucial roles in host-seeking, detection of oviposition
attractants, etc., However, information about the role of OBP2 in A. gossypii
(AgOBP2) is still unavailable. In this study, we cloned and characterized OBP2,
ortholog from A. gossypii, and the full-length AgOBP2 complementary DNA (cDNA)
consisted of 859 bp with an open reading frame of 732 bp. Phylogenetic analysis
resulted in grouping of AgOBP2 protein with members of the tribe Aphidini.
Further, diet-mediated delivery of double-stranded RNA for AgOBP2 induced
silencing, which was evaluated at 48 and 96 h. The reverse transcriptase real
time quantitative polymerase chain reaction (RTq-PCR) results revealed that the
level of AgOBP2 messenger RNA (mRNA) was significantly reduced (55-77 %) in
dsAgOBP2 treatment after 96 h as compared to the untreated control. The same was
reiterated by the electrophysiological responses in the aphids which was reduced
(>50 % at 0.25 MUg/MUl concentration) as compared to the untreated control. Thus,
our results showed the potential of gene silencing, possibly to interfere with
the odorant perception of A. gossypii for RNAi-mediated pest management. The
results from our study provided the first evidence that AgOBP2 play crucial roles
in host-seeking, detection of oviposition attractants, etc.; as a result, we
suggests that OBP2 could potentially serve as a practicable target for RNAi
mediated gene silencing in hemipteran insect pest control.
PMID- 26432292
TI - Glycoproteins and Gal-GalNAc cause Cryptosporidium to switch from an invasive
sporozoite to a replicative trophozoite.
AB - The apicomplexan parasite Cryptosporidium causes cryptosporidiosis, a diarrheal
disease that can become chronic and life threatening in immunocompromised and
malnourished people. There is no effective drug treatment for those most at risk
of severe cryptosporidiosis. The disease pathology is due to a repeated cycle of
host cell invasion and parasite replication that amplifies parasite numbers and
destroys the intestinal epithelium. This study aimed to better understand the
Cryptosporidium replication cycle by identifying molecules that trigger the
switch from invasive sporozoite to replicative trophozoite. Our approach was to
treat sporozoites of Cryptosporidium parvum and Cryptosporidium hominis, the
species causing most human cryptosporidiosis, with various media under axenic
conditions and examine the parasites for rounding and nuclear division as markers
of trophozoite development and replication, respectively. FBS had a concentration
dependent effect on trophozoite development in both species. Trophozoite
development in C. parvum, but not C. hominis, was enhanced when RPMI supplemented
with 10% FBS (RPMI-FBS) was conditioned by HCT-8 cells for 3h. The effect of non
conditioned and HCT-8 conditioned RPMI-FBS on trophozoite development was
abrogated by proteinase K and sodium metaperiodate pretreatment, indicating a
glycoprotein trigger. Cryptosporidium parvum and C. hominis trophozoite
development also was triggered by Gal-GalNAc in a concentration-dependent manner.
Cryptosporidium parvum replication was greatest following treatments with Gal
GalNAc, followed by conditioned RPMI-FBS and non-conditioned RPMI-FBS (P<0.05).
Cryptosporidium hominis replication was significantly less than that in C. parvum
for all treatments (P<0.05), and was greatest at the highest tested concentration
of Gal-GalNAc (1mM).
PMID- 26432293
TI - Intestinal microbes influence the survival, reproduction and protein profile of
Trichinella spiralis in vitro.
AB - The interactions between intestinal microbes and parasitic worms play an
essential role in the development of the host immune system. However, the effects
of gut microbes on Trichinella spiralis are unknown. The aim of this work was to
explore microbe-induced alterations in the survival and reproduction of T.
spiralis in vitro. To further identify the proteins and genes involved in the
response of nematodes to microbes, quantitative proteomic analysis of T. spiralis
was conducted by iTRAQ-coupled LCMS/MS technology and quantitative real-time-PCR
was used to measure changes in mRNA expression. The results showed Lactobacillus
acidophilus, and especially Lactobacillus bulgaricus, significantly enhanced the
survival and reproductive rates of nematodes. Salmonella enterica, and especially
Escherichia coli O157:H7 (EHEC), had opposite effects. Genetic responses were
activated mainly by EHEC. A total of 514 proteins were identified and quantified,
and carbohydrate metabolism-related proteins existed in a higher proportion.
These findings indicated that some gut bacteria are friendly or harmful to humans
and in addition they may have similar beneficial or detrimental effects on
parasites. This may be due to the regulation of expression of specific genes and
proteins. Our studies provide a basis for developing therapies against parasitic
infections from knowledge generated by studying the gut microbes of mammals.
PMID- 26432294
TI - Estimates of coextinction risk: how anuran parasites respond to the extinction of
their hosts.
AB - Amphibians are known as the most threatened vertebrate group. One of the outcomes
of a species' extinction is the coextinction of its dependents. Here, we estimate
the extinction risk of helminth parasites of South America anurans. Parasite
coextinction probabilities were modeled, assuming parasite specificity and host
vulnerability to extinction as determinants. Parasite species associated with few
hosts were the most prone to extinction, and extinction risk varied amongst
helminth species of different taxonomic groups and life cycle complexity.
Considering host vulnerability in the model decreased the extinction probability
of most parasites species. However, parasite specificity and host vulnerability
combined to increase the extinction probabilities of 44% of the helminth species
reported in a single anuran species.
PMID- 26432295
TI - Vasoconstriction induced by salivary gland extracts from ixodid ticks.
AB - In their quest for blood, most haematophagous parasites secrete vasodilators in
their saliva to counter the host haemostatic response of vasoconstriction.
Surprisingly, salivary gland extracts from adult female Dermacentor reticulatus
and Rhipicephalus appendiculatus ticks induced constriction in a rat femoral
artery model; males induced vasoconstriction or vasodilation depending on the
time of feeding. Based on comparative HPLC fractionation, the active compounds
inducing vasoconstriction do not appear to be prostaglandins (which ticks
normally use as vasodilators). Vasoconstriction may be unique to ixodid ticks,
helping them control blood flow during their prolonged blood-feeding of up to 10
days or more.
PMID- 26432296
TI - The miRnome of Fasciola hepatica juveniles endorses the existence of a reduced
set of highly divergent micro RNAs in parasitic flatworms.
AB - The liver fluke Fasciola hepatica is a foodborne zoonotic parasite affecting
livestock worldwide, with increasing relevance in human health. The first
developmental stage that the host meets after ingestion of the parasite is the
newly excysted juvenile, that actively transverses the gut wall and migrates to
its final location in the liver. The regulation of the early developmental events
in newly excysted juveniles is still poorly understood and a relevant target for
control strategies. Here we investigated the putative involvement of small
regulatory RNAs in the invasion process. The small RNA population of the newly
excysted juvenile fall into two classes, one represented by micro (mi)RNAs and a
secondary group of larger (32-33 nucleotides) tRNA-derived sequences. We
identified 40 different miRNAs, most of those belonging to ancient miRNAs
conserved in protostomes and metazoans, notably with a highly predominant miR
125b variant. Remarkably, several protostomian and metazoan conserved families
were not detected in consonance with previous reports of drastic miRnome
reduction in parasitic flatworms. Additionally, a set of five novel miRNAs was
identified, probably associated with specific gene regulation expression needs in
F. hepatica. While sequence conservation in mature miRNA is high across the
metazoan tree, we observed that flatworm miRNAs are more divergent, suggesting
that mutation rates in parasitic flatworms could be high. Finally, the
distinctive presence of tRNA-derived sequences, mostly 5' tRNA halves of selected
tRNAs in the small RNA population of newly excysted juveniles, raises the
possibility that both miRNA and tRNA fragments participate in the regulation of
gene expression in this parasite.
PMID- 26432297
TI - Effect of angiotensin II-induced arterial hypertension on the voltage-dependent
contractions of mouse arteries.
AB - Arterial hypertension (AHT) affects the voltage dependency of L-type Ca(2+)
channels in cardiomyocytes. We analyzed the effect of angiotensin II (AngII)
induced AHT on L-type Ca(2+) channel-mediated isometric contractions in conduit
arteries. AHT was induced in C57Bl6 mice with AngII-filled osmotic mini-pumps (4
weeks). Normotensive mice treated with saline-filled osmotic mini-pumps were used
for comparison. Voltage-dependent contractions mediated by L-type Ca(2+) channels
were studied in vaso-reactive studies in vitro in isolated aortic and femoral
arteries by using extracellular K(+) concentration-response (KDR) experiments. In
aortic segments, AngII-induced AHT significantly sensitized isometric
contractions induced by elevated extracellular K(+) and depolarization. This
sensitization was partly prevented by normalizing blood pressure with
hydralazine, suggesting that it was caused by AHT rather than by direct AngII
effects on aortic smooth muscle cells. The EC50 for extracellular K(+) obtained
in vitro correlated significantly with the rise in arterial blood pressure
induced by AngII in vivo. The AHT-induced sensitization persisted when aortic
segments were exposed to levcromakalim or to inhibitors of basal nitric oxide
release. Consistent with these observations, AngII-treatment also sensitized the
vaso-relaxing effects of the L-type Ca(2+) channel blocker diltiazem during K(+)
induced contractions. Unlike aorta, AngII-treatment desensitized the isometric
contractions to depolarization in femoral arteries pointing to vascular bed
specific responses of arteries to hypertension. AHT affects the voltage-dependent
L-type Ca(2+) channel-mediated contraction of conduit arteries. This effect may
contribute to the decreased vascular compliance in AHT and explain the efficacy
of Ca(2+) channel blockers to reduce vascular stiffness and central blood
pressure in AHT.
PMID- 26432299
TI - Dr Edgar R. R. Parker: his time and now.
PMID- 26432298
TI - Determinants of utilisation of antenatal care and skilled birth attendant at
delivery in South West Shoa Zone, Ethiopia: a cross sectional study.
AB - BACKGROUND: Ethiopia has high maternal mortality ratio and poor access to
maternal health services. Attendance of at least four antenatal care (ANC) visits
and delivery by a skilled birth attendant (SBA) are important in preventing
maternal deaths. Understanding the reasons behind the poor use of these services
is important in designing strategies to address the problem. This study aimed to
determine the coverage of at least four ANC visits and delivery by a SBA and to
identify determinants of utilisation of these services in three districts in
South West Shoa Zone, Ethiopia. METHODS: A cross-sectional survey of 500 women
aged 15-49 years with a delivery in two years prior to the survey was conducted
in Wolisso, Wonchi and Goro districts in February 2013. Data were collected using
an interviewer administered questionnaire. Logistic regression models were used
to explore determinants of ANC attendance and SBA at delivery. RESULTS: Coverage
of at least four ANC visits and SBA at delivery were 45.5 and 28.6 %,
respectively. Most institutional deliveries (69 %) occurred at the single
hospital that serves the study districts. Attendance of at least four ANC visits
was positively associated with wealth status, knowledge of the recommended number
of ANC visits, and attitude towards maternal health care, but was negatively
associated with woman's age. SBA at delivery was negatively associated with
parity and time to the health facility, but was positively associated with urban
residence, wealth, knowledge of the recommended number of ANC visits, perceived
good quality of maternal health services, experience of a pregnancy/delivery
related problem, involvement of the partner/family in decision making on delivery
place, and birth preparedness. CONCLUSIONS: Raising awareness about the minimum
recommended number of ANC visits, tackling geographical inaccessibility,
improving the quality of care, encouraging pregnant women to have a birth and
complication readiness plan and community mobilisation targeting women, husbands,
and families for their involvement in maternal health care have the potential to
increase use of maternal health services in this setting. Furthermore, supporting
health centres to increase uptake of institutional delivery services may rapidly
increase coverage of delivery by SBA and reduce inequity.
PMID- 26432300
TI - The cleft child.
PMID- 26432301
TI - Matched, equal, equipoise.
PMID- 26432302
TI - Postsurgical volumetric airway changes in 2-jaw orthognathic surgery patients.
PMID- 26432303
TI - Authors' response.
PMID- 26432304
TI - The 101st man of influence.
PMID- 26432305
TI - Diversified rapid maxillary expander or utility maxillary expander?
PMID- 26432307
TI - Without undue influence.
PMID- 26432308
TI - T.M. "Tom" Graber: a passion for orthodontics.
PMID- 26432309
TI - Viken Sassouni: scientist, teacher, and mentor.
PMID- 26432310
TI - Overview of orthodontic care for children with cleft lip and palate, 1915-2015.
AB - The purpose of this article is to review and discuss the advances in the
management of children born with cleft lip and palate (CLP) as it has evolved
over the past 100 years. This overview is based on articles published in the
American Journal of Orthodontics, which frequently changed its name, over the
past century. Additionally, other journals will be cited as craniofacial
anomalies became recognized during the 20th century and the biologic basis became
refined, with the new discipline of genetics replacing the term hereditary and
its connotations of eugenics. The Human Genome Project, completed in 2003, has
now provided an understanding of syndromic and nonsyndromic CLP that has led to
advances in the diagnosis and treatment of CLP in the 21st century. These
evolving concepts will be discussed in an overview of the types of procedures
published from 1915 to 2015 and the major transition in the mid-20th century from
multiple uncoordinated interventions from various specialists to a coordinated
team approach in which the orthodontist has a specific role in the timing and
sequencing of interdisciplinary treatment goals. Major technologic advancements
in treatment modalities and the contemporary approach to the health-related
quality of life of the patient and the caregiver have resulted in their
participation in treatment options and decisions. The requirement of informed
consent reflects the legal doctrine that now emphasizes the ethical imperative of
greater respect for patient autonomy in the decision-making process. The
orthodontist no longer makes decisions alone, but rather with the team and the
patient or the caregiver.
PMID- 26432311
TI - Etiology of maxillary canine impaction: a review.
AB - This article is a review that enumerates the causes of impaction of the maxillary
permanent canines, including hard tissue obstructions, soft tissue lesions, and
anomalies of neighboring teeth, and discusses the much-argued relationship
between environmental and genetic factors. These phenomena have been shown in
many investigations to accompany the diagnosis of canine impaction and have been
presented as unrelated anomalous features, each of which is etiologically
construed as genetic, including the aberrant canine itself. While in general the
influence of genetics pervades the wider picture, a guidance theory proposes an
alternative etiologic line of reasoning and interpretation of these studies, in
which the same genetically determined anomalous features provide an abnormal
milieu in which the canine is reared and from which it is guided in its
misdirected and often abortive path of eruption.
PMID- 26432312
TI - Oral health-related quality of life changes in standard, cleft, and surgery
patients after orthodontic treatment.
AB - INTRODUCTION: The purpose of this study was to investigate the effect of
orthodontic treatment on oral health-related quality of life (OHRQoL) in groups
of standard patients with severe malocclusions; cleft lip, cleft palate, or cleft
lip and palate patients; and orthognathic surgery patients. METHODS: The study
sample consisted of 83 consecutive patients undergoing treatment at the
orthodontic unit of Christchurch Hospital, Christchurch, New Zealand, divided
into 3 groups: 30 adolescents with severe malocclusions; 24 adolescents with
cleft lip, cleft palate, or cleft lip and palate; and 29 adults with severe
skeletal discrepancies requiring both orthognathic surgery and orthodontic
treatment. Each patient completed the Short Form of the Oral Health Impact
Profile (OHIP-14) questionnaire before and after orthodontic treatment. RESULTS:
The baseline OHIP-14 subscale scores among the 3 study groups were significantly
different, with the surgery patients having nearly twice the OHIP-14 scores of
the other 2 groups for nearly half of the items (P <0.05). The surgery patients
experienced the greatest reduction in OHIP-14 scores (ie, improvement in OHRQoL),
with the largest effect sizes reported for the psychological discomfort (+2.73)
and disability (+2.65) domains. The group with clefts experienced the smallest
changes in OHIP-14 scores across all 7 domains (-0.03 to +0.63). After adjusting
for age and sex, the surgical patients had a significantly greater reduction in
pretreatment OHIP-14 scores than did the standard and the cleft patients (P
<0.01). CONCLUSIONS: The effect of orthodontic treatment on OHRQoL varies for
different patient groups even after adjusting for age and sex. The greatest
improvement in OHRQoL occurred in adults with a need for orthognathic surgery,
whereas the least improvement seemed to occur in adolescents with cleft lip,
cleft palate, or cleft lip and palate.
PMID- 26432313
TI - Growth-related changes of skeletal and upper-airway features in bilateral cleft
lip and palate patients.
AB - INTRODUCTION: The craniofacial morphology of subjects with cleft lip and palate
differs from that of subjects without clefts. Subjects with bilateral cleft lip
and palate tend to have maxillary retrognathism, a smaller mandible with an
obtuse gonial angle, greater anterior upper and lower facial heights, and
retroclined maxillary incisors. The purposes of this research were to compare the
skeletal and upper-airway features of subjects with bilateral cleft lip and
palate with the same features in control subjects without clefts and to determine
the growth-related changes at different growth stages. METHODS: The sample
comprised 212 subjects divided into 2 groups: 68 with bilateral cleft lip and
palate, and 144 controls without clefts; each group was further divided into 4
subgroups according to growth stage using the cervical vertebral maturation stage
method. The subgroups were defined as early childhood (stage 1), prepubertal
(stage 2), pubertal (stage 3), and postpubertal (stage 4). The cephalometric
variables were evaluated with 2-way analysis of variance and the Bonferroni test.
RESULTS: Maxillary position showed no significant differences between the male
groups. The maxilla was more prognathic at stage 2 and became more retrognathic
at stages 3 and 4 in the females. The mandible was more retrusive in the
bilateral cleft lip and palate subjects at stage 1 in males and at stages 3 and 4
in females. ANB was larger at stages 1 and 2, and it became similar to the
controls at stages 3 and 4 in male and female bilateral cleft lip and palate
subjects. Vertical growth was seen in the bilateral cleft lip and palate subjects
regardless of sex, and no change was observed with age. Posterior airway space
was narrower in all stages (except for stage 1 in females). Middle airway space
was wider after stage 1 in the male and female bilateral cleft lip and palate
subjects. Inferior airway space was narrower in the male bilateral cleft lip and
palate patients at the early childhood and pubertal stages. CONCLUSIONS: Age- and
sex-dependent differences in skeletal morphology and upper-airway widths of the
bilateral cleft lip and palate subjects were identified when compared with the
control subjects without clefts.
PMID- 26432314
TI - Evaluation of root and alveolar bone development of unilateral osseous impacted
immature maxillary central incisors after the closed-eruption technique.
AB - INTRODUCTION: In this study, we evaluated root and alveolar bone development in
unilateral osseous impacted immature maxillary central incisors by cone-beam
computed tomography before and after closed-eruption treatment, in comparison
with naturally erupted contralateral immature maxillary central incisors. METHODS
AND RESULTS: The study included 30 patients, 20 boys and 10 girls, with a mean
age of 8.44 +/- 1.20 years (range, 6.5-11.2 years). After treatment, the root
lengths of both the impacted maxillary central incisors (10.66 +/- 2.10 mm) and
the contralateral maxillary central incisors (11.04 +/- 1.76 mm) were
significantly greater than their pretreatment values (6.67 +/- 1.94 and 9.02 +/-
2.13 mm, respectively). The root canal widths of the incisors decreased
significantly after treatment. From the posttreatment cone-beam computed
tomography images, the ratio of exposed root length to total root length and the
thickness of the alveolar bone at 1 mm under the alveolar crest and at the apex
were calculated to evaluate alveolar bone development. Impacted immature
maxillary central incisors differed significantly from contralateral immature
maxillary central incisors in labial exposed root length, labial ratio to total
root length, and lingual alveolar crest. Clinical crown height was higher
(statistically but not clinically) for the impacted incisors (9.87 mm) than for
the contralateral incisors (9.37 mm). CONCLUSIONS: Impacted immature incisors
grew to the same stage as did erupted contralateral incisors after closed
eruption treatment. Both incisor types had some alveolar bone loss, and thin
alveolar bone surrounded the roots.
PMID- 26432315
TI - Comparison of transverse changes during maxillary expansion with 4-point bone
borne and tooth-borne maxillary expanders.
AB - INTRODUCTION: The purposes of this study were to evaluate and compare the
dentoskeletal changes concurrent with 4-point bone-borne and tooth-borne rapid
maxillary expanders in growing children. METHODS: The study was conducted with 20
growing girls (ages, 12 +/- 0.6 years) with posterior crossbite. They were
divided into 2 equal groups; patients in one group were treated with a tooth
borne maxillary hyrax expander (TBME), and those in the other group received a
bone-borne maxillary hyrax expander (BBME) anchored directly to the palatal bone.
Changes were assessed using cone-beam computed tomography. Images were taken
before and immediately after expansion. RESULTS: Superimpositions of the 3
dimensional palatal images showed significant increases in skeletal widths at the
canine, first premolar, and first molar areas in both groups. The TBME group had
greater nasal width expansion. Regarding the transverse dentolinear measurements,
significant increases were seen in both groups, whereas the TBME group showed a
greater increase than the BBME group. Significant increases in the dentoangular
measurements were seen in the TBME group only and were significantly greater than
in the BBME group at the first premolars. CONCLUSIONS: There were significant
increases in facial and maxillary widths for the BBME group and in nasal width
for the TBME group. Both expanders produced basal bone expansion at the level of
the hard palate. The TBMEs produced more dental expansion, buccal rolling, and a
greater increase in nasal width than did the BBMEs.
PMID- 26432316
TI - Effect of low-level laser therapy on orthodontic tooth movement into bone-grafted
alveolar defects.
AB - INTRODUCTION: The objective of this study was to investigate the effect of low
level laser therapy (LLLT) on the rate of orthodontic tooth movement (OTM) into
bone-grafted alveolar defects based on different healing states. METHODS: Ten
male beagles were randomly allocated to 3 groups: group C, OTM alone as a
control; group G, OTM into the grafted defects; group GL, OTM into the grafted
defects with LLLT. The maxillary second premolars were protracted into the
defects for 6 weeks, immediately (G-0 and GL-0) and at 2 weeks (G-2 and GL-2)
after surgery. The defects were irradiated with a diode laser (dose, 4.5 J/cm(2))
every other day for 2 weeks. The rates of OTM and alveolar bone apposition, and
maturational states of the defects were analyzed by histomorphometry,
microcomputed tomography, and histology. RESULTS: The total amounts of OTM and
new bone apposition rates were decreased by LLLT, with increased bone mineral
density and trabecular maturation in the defects. Group GL-2 had the slowest
movement with root resorption in relation to less woven bone in the hypermatured
defect. CONCLUSIONS: LLLT significantly decreased the rate of OTM into the bone
grafted surgical defects by accelerating defect healing and maturation,
particularly when the start of postoperative OTM was delayed.
PMID- 26432317
TI - Effect of physical activity level on orthodontic pain perception and analgesic
consumption in adolescents.
AB - INTRODUCTION: The objective of this study was to assess the effect of baseline
physical activity level on orthodontic pain perception and analgesic consumption
after orthodontic separator placement in adolescents. METHODS: One hundred fifty
participants (mean age, 14.5 years; SD, 1.7 years; 73 girls, 77 boys) were
included in this longitudinal study. The physical activity questionnaire was used
to assess their baseline physical activity levels. Once participants completed
the questionnaire, orthodontic separators were placed at the mesial and distal
contact points of the maxillary and mandibular first molars. A 100-mm visual
analog scale was used for pain assessment. Analgesic consumption was recorded as
a binary response (yes/no). Both outcomes were assessed at 1 baseline time point
and 7 follow-up time points (bedtime on days 1 to 7). A multilevel mixed-effect
model analysis approach was used to analyze the longitudinal data. RESULTS: Of
the 150 participants in the study, data from 137 were included in the analysis
(mean age, 14.4 years; SD, 1.7 years; 65 girls, 72 boys). Compared with the low
activity group (84 participants; 61.3%), the high-activity group (53
participants; 38.7%) experienced significantly less pain (mean estimate, -8.958;
P = 0.0114; 95% confidence interval, -15.868 to -2.049) and consumed fewer
analgesics (odds ratio, 0.443; P <0.0318; 95% confidence interval, 0.199 to
0.786) during the study period. CONCLUSIONS: Physical activity has a significant
influence on orthodontic pain perception and analgesic consumption in adolescents
undergoing orthodontic treatment. Further research is needed on this topic to
elucidate the association between physical activity and orthodontic pain.
PMID- 26432318
TI - Compliance by state-subsidized and self-pay orthodontic patients.
AB - INTRODUCTION: Medicaid is a needs-based program in the United States that
subsidizes medical and dental care for minors. The purpose of this study was to
test for compliance differences between self-pay and Medicaid-supported patients.
METHODS: Medicaid patient records (n = 88) were perused retrospectively for
characteristics that distract from an orthodontist's workflow (missed
appointments, broken brackets, treatment duration, and so on) and compared with a
sample (n = 145) of self-pay patients from the same teaching clinic. Differences
in treatment difficulty were adjusted by subject selection and statistically
(analysis of covariance). RESULTS: Medicaid patients were younger (mean age, 14.1
vs 14.9 years) and significantly more likely to be dismissed from treatment (19%
vs 4%), generally for noncompliance. Broken brackets and missed appointments were
more common in the Medicaid sample. There was no difference in the number of
appointments in those completing treatment, but treatment duration was
significantly longer for the Medicaid patients who completed treatment (29 vs 25
months). Commute distance and estimated driving time were significantly shorter
for the Medicaid-assisted group. CONCLUSIONS: Greater difficulty in managing
Medicaid patients may partly explain why they are underserved. Prospective
studies are needed to clarify the causes of the differences.
PMID- 26432319
TI - Mandibular changes secondary to serial extractions compared with late premolar
extractions and controls.
AB - INTRODUCTION: Variations in treatment times for serial extraction and late
premolar extraction patients may be due to differences in the time needed to
flatten the occlusal curves. In this study, we compared tooth tipping and
occlusal curves in patients treated by serial extractions or late premolar
extractions with untreated controls. METHODS: Mandibular dental casts and
cephalometric radiographs were collected from 90 subjects (30 Class I control
subjects, 30 patients with serial extractions, and 30 with late premolar
extractions) at 3 time points: T0, baseline for the controls and serial
extraction patients; T1, after natural drift and preorthodontics for the controls
and the serial extraction patients, and pretreatment for the late premolar
extraction patients; and T2, after comprehensive orthodontic treatment for the
serial extraction and the late premolar extraction groups. The long axes of the
central incisor, canine, and first molar to the palatal plane were measured on
digitized headfilms to determine the direction and the amount of tipping between
the time points. Three occlusal curves were measured by sphere fitting cusp-tip
landmarks on digitized mandibular casts. RESULTS: From T0 to T1, incisors and
canines in the patients with serial extractions tipped distally. Molars at T1 in
the patients with serial extractions were tipped forward more than in the late
premolar extraction patients and the controls. From T1 to T2, canines and molars
in the patients with serial extractions were uprighted. CONCLUSIONS: Serial
extractions produce steeper occlusal curves and distal tipping of the incisors
and canines after drift (T1). Posttreatment (T2) occlusal curves in the patients
with serial extractions are steeper than in the late premolar extraction patients
and controls (except for the curve of Spee). After the serial extractions,
orthodontic treatment included incisor and canine proclination, with molar
uprighting and occlusal curve flattening.
PMID- 26432320
TI - Effect of maxillary protraction with alternating rapid palatal expansion and
constriction vs expansion alone in maxillary retrusive patients: a single-center,
randomized controlled trial.
AB - INTRODUCTION: The objective of this randomized controlled trial was to
investigate the effects of facemask protraction combined with alternating rapid
palatal expansion and constriction (RPE/C) vs rapid palatal expansion (RPE) alone
in the early treatment of maxillary retrusive patients. METHODS: Patients with a
midface deficiency were recruited and randomly allocated into either the control
group (RPE) or the intervention group (RPE/C). Eligibility criteria included the
following: age 7 to 13 years old, Class III malocclusion, anterior crossbite, ANB
less than 0 degrees , Wits appraisal less than -2 mm, A-Np less than 0 mm, and no
cleft of lip or palate. The primary outcome was the degree of maxillary forward
movement after treatment. The secondary outcomes were the changes of the other
cephalometric variables after treatment and the treatment time. Simple
randomization was carried out using a random number table at the beginning of the
study. Envelopes containing the grouping information were used to ensure
allocation concealment from the researchers. Blinding was applicable for
cephalometric analysis only. Hyrax palatal expanders and facemask maxillary
protraction were used in all patients. Patients in the RPE group were treated
with rapid palatal expansion for 1 week. Patients in the RPE/C group were treated
with RPE/C for 7 weeks. The expansion or constriction rate was 1 mm per day.
Cephalometric analysis with traditional cephalometric measurements and an x-y
coordinate system were used to compare the pretreatment and posttreatment
cephalometric radiographs. Independent t tests were used to compare the data
between the 2 groups. RESULTS: A total of 44 patients were randomized to either
the RPE group or the RPE/C group in a 1:1 ratio. One subject in the RPE group was
lost to follow-up during the treatment. Per-protocol analysis was used. All the
other 43 patients reached the treatment completion criteria and were analyzed
(RPE group: n = 21; RPE/C group: n = 22). The average protraction time was 10.84
months in the RPE group, which was significantly longer than that in the RPE/C
group (9.06 months) (effect size [ES], 1.78 [95% CI, 0.15, 3.42; P = 0.033]).
Maxillary forward movement increased by 3.04 mm in the RPE/C group, which was
significantly greater than that in the RPE group (2.11 mm) (ES, -0.93 [95% CI,
1.65, -0.20; P = 0.013]). The counterclockwise rotation of the palatal plane was
1.73 degrees in the RPE/C group, which was significantly greater than that in
the RPE group (0.83 degrees ) (ES, 0.90 [95% CI, 0.08, 1.73; P = 0.033]). The
degree of mandibular downward and backward rotation was significantly smaller in
the RPE/C group (P <0.05). No serious harm was observed during treatment and
research. CONCLUSIONS: Facemask maxillary protraction with RPE/C might positively
affect the forward movement of the maxilla compared with facemask protraction
with RPE alone in the early treatment of maxillary retrusive patients. Although
the differences between the groups were statistically significant for forward
movement of the maxilla and rotation of the palatal and mandibular planes, these
may not be clinically relevant, since the differences were less than 1 mm and 1
degrees , respectively. REGISTRATION: This trial was not registered. PROTOCOL:
The protocol was not published before trial commencement. FUNDING: This research
was supported by Peking University Research Fund. No conflict of interest is
declared.
PMID- 26432321
TI - Factors associated with patient and parent satisfaction after orthodontic
treatment: a systematic review.
AB - INTRODUCTION: Our objective was to identify factors associated with orthodontic
treatment satisfaction of patients and their caregivers, when applicable.
METHODS: MEDLINE via Ovid, PubMed, EBM Reviews and EMBASE via OVIDSP, LILACS, Web
of Science, and Google Scholar were searched electronically. Reference lists of
included articles were also screened for potential relevant studies missed during
the electronic searches. Studies evaluating the satisfaction levels of patients
or caregivers after orthodontic treatment were considered. Methodologic quality
of the included studies was assessed using a modified Newcastle-Ottawa scale.
RESULTS: Eighteen studies satisfied the inclusion criteria, representing 2891
patients and 464 parents. The risk of bias was moderate in 13 and low in 4 of the
included articles. The studies used different questionnaires and timings to
assess postorthodontic treatment satisfaction. Based on the available limited
evidence, satisfaction was associated with perceived esthetic outcomes,
psychological benefits, and quality of care. The latter was specifically linked
to dentist-staff-patient interactions. Dissatisfaction was associated with
treatment duration, pain levels and discomfort, and the use of retention
appliances. When both assessments were available, the patient's and the parent's
satisfaction levels were strongly correlated. CONCLUSIONS: Based on the limited
available evidence with moderate risk of bias, we identified factors that appear
to be more commonly associated with a high or low level of satisfaction.
Consideration of these factors could be important for practitioners attempting to
set realistic expectations of their patients and caregivers regarding orthodontic
treatment outcomes.
PMID- 26432322
TI - Treatment of a mandibular functional shift in an adolescent boy with
temporomandibular disorder and crossbites.
AB - A mandibular functional shift usually poses a challenge for orthodontists,
especially when it is accompanied by a temporomandibular disorder (TMD). Accurate
diagnosis and complete elimination of the etiologic factors are the keys to an
esthetic and stable outcome. This article describes the treatment of a teenager
with a mandibular functional shift, TMD symptoms, and facial asymmetry resulting
from an asymmetric maxillary arch form and multiple crossbites as occlusal
interferences. The treatment alternatives and effective orthodontic techniques
are described. To optimize the treatment results and prevent the recurrence of
the TMD after treatment, the displaced mandible was repositioned by full-time
wearing of a splint for 10 months. Adhesive bite-blocks were used to maintain the
newly acquired mandibular position during fixed appliance treatment. A series of
nickel-titanium and stainless steel rectangular archwires was placed in the
maxillary arch to reshape it for 8 months after alignment. Finally, the displaced
mandible was steadily seated into its physiologic position with fine occlusion.
The TMD symptoms disappeared and never relapsed after treatment. At 2 years 3
months of retention, there was good stability. The combined splint and fixed
appliance approach resolved an intractable clinical problem and avoided using
additional appliances. An esthetic, functional, and stable outcome was achieved
that satisfied both the patient and his parents.
PMID- 26432323
TI - Sagittal correction of adolescent patients with modified palatal anchorage plate
appliances.
AB - The palate has been reported to be a suitable skeletal anchorage site in
adolescents and adults. This article introduces new treatment modalities for
correction of sagittal discrepancies by molar protraction and distalization with
a modified palatal anchorage plate appliance. The effectiveness and versatility
of this method are demonstrated in 2 adolescent patients.
PMID- 26432324
TI - Impact on perceived root resorption based on the amount of incisal inclination as
determined from conventional panoramic radiography.
AB - INTRODUCTION: Our objective was to measure the impact on perceived root
resorption based on the amount of anteroposterior incisal inclination as
determined in vitro from conventional panoramic radiography. METHODS: A rapid
prototyping model was created to mimic different maxillary and mandibular incisal
anteroposterior inclinations. Two titanium beads were placed on the incisors at
the apical and incisal edges. Panoramic radiographs were obtained, with the
incisors changing relative inclination by 10 degrees increments. The length was
measured from the midpoint of the bead on the incisal edge to the midpoint of the
bead on the apical edge. By using a length of wire of known size, this value was
compared in all images to correct for image magnification. RESULTS: Changes to
mandibular incisor anteroposterior inclinations, as either a theoretical
proclination or retroclination, resulted in an increase of "apparent" root
resorption on a panoramic radiograph. When the maxillary incisors were
significantly and severely retroclined, they appeared larger than expected. When
the maxillary incisors were mildly retroclined, the length was roughly similar to
the theoretical model. When the maxillary incisors were mildly proclined, they
appeared shorter than expected. CONCLUSIONS: The foreshortening or
forelengthening of incisor root lengths because of incisor inclination vs root
resorption cannot be reliably evaluated from panoramic images. The proposed
theoretical model helps to understand the direction of the changes produced by
the magnification factor. More severe scenarios where either the maxillary or the
mandibular teeth are outside the focal trough have not been fully evaluated. The
clinical impact of these changes is likely to be questionable.
PMID- 26432325
TI - Litigation and Legislation. Heeding the advice of others.
PMID- 26432326
TI - Nonparametric methods.
PMID- 26432327
TI - International Day of Radiology 2015.
PMID- 26432328
TI - Hsp90 regulates autophagy and plays a role in cancer therapy.
AB - Nowadays, heat shock protein 90 (Hsp90), a highly conserved molecular chaperone,
has become the target of antitumor drugs as a result of its close relationship
with the occurrence and development, biological behavior, and prognosis of a
tumor. Autophagy has attracted big attention recently for its paradoxical roles
in cell survival and cell death, especially in the pathogenesis and treatment of
cancer. Moreover, it has been verified that Hsp90 plays a role in autophagy via
regulating the stability and activity of signaling proteins, and some Hsp90
inhibitors can induce autophagy. However, the underlying mechanisms for these
important processes have not been clarified so far. In this study, we focus on
the roles of Hsp90 in the regulation of autophagy, such as toll-like receptor
(TLR)-mediated autophagy, Ulk1-mediated mitophagy, and chaperone-mediated
autophagy (CMA). The roles of Hsp90 inhibitors in cancer therapy will also be
elucidated.
PMID- 26432330
TI - Authentication of newly established human esophageal squamous cell carcinoma cell
line (YM-1) using short tandem repeat (STR) profiling method.
AB - Cross-contamination during or early after establishment of a new cell line could
result in the worldwide spread of a misidentified cell line. Therefore, newly
established cell lines need to be authenticated by a reference standard method.
This study was conducted to investigate the authenticity of a newly established
epithelial cell line of human esophageal squamous cell carcinoma (ESCC) called YM
1 using short tandem repeat (STR) DNA profiling method. Primary human ESCC
epithelial cells were cultured from the fresh tumor tissue of an adult female
patient. Growth characteristics and epithelial originality of YM-1 cells were
studied. Genomic DNA was isolated from YM-1 cells harvested at passage 22 and
ESCC donor tumor sample on two different days to prevent probable DNA
contamination. STR profiling was performed using AmpFlSTR(r) Identifiler(r) Plus
PCR Amplification Kit. To address whether YM-1 cells undergo genetic alteration
as the passage number increases, STR profiling was performed again on harvested
cells at passage 51. YM-1 cells grew as a monolayer with a population doubling
time of 40.66 h. Epithelial originality of YM-1 cells was confirmed using ICC/IF
staining of cytokeratins AE1/AE3. The STR profile of the ESCC donor tumor sample
was the same with YM-1 cells at passage 22. However, STR profile of the donor
tumor sample showed an off-ladder (OL) allele in their D7S820 locus. Also, re
profiling of YM-1 cells at passage 51 showed a loss of heterozygosity (LOH) at
D18S51 locus. This suggests that long-term culture of cell lines may alter their
DNA profile. Comparison of the DNA fingerprinting results in DSMZ, and ATCC STR
profiling databases confirmed unique identity of YM-1 cell line. This study
provides an easy, fast, and reliable procedure for authentication of newly
established cell lines, which helps in preventing the spread of misidentified
cells and improving the reproducibility and validity of experiments,
consequently.
PMID- 26432329
TI - Silencing of FGFR4 could influence the biological features of gastric cancer
cells and its therapeutic value in gastric cancer.
AB - To clarify the role of fibroblast growth factor receptor 4 (FGFR4) in gastric
cancer (GC) and explore the therapeutic value of BGJ398 targeted to FGFR4. We
constructed lentivirus vectors to stably knockdown FGFR4 expression in GC cells.
Function assays in vitro and in vivo, treated with 5-fluorouracil (5-Fu) and
BGJ398, were performed to study the change of biological behaviors of GC cells
and related mechanism. The proliferation and invasive ability of HGC27 and MKN45
significantly decreased while the apoptosis rate of GC cells obviously increased
in shRNA group (P < 0.05). The expressions of Bcl-xl, FLIP, PCNA, vimentin, p
erk, and p-STAT3 significantly reduced while the expressions of caspase-3 and E
cadherin markly enhanced in shRNA group. The proliferation abilities of GC cells
were more significantly inhibited by the combination of BGJ398 and 5-Fu in shRNA
group (P < 0.05). Compared to negative control (NC), the single and combination
of 5-Fu and BGJ398 all significantly increased the apoptosis rate of GC cells,
especially in the combination group (P < 0.01). The single and combination of 5
Fu and BGJ398 decreased the expressions of PCNA, Bcl-xl, and FLIP while increased
the expression of caspase-3 in GC cells, especially in shRNA groups. Furthermore,
knockdown of FGFR4 expression might prevent the growth of GC in vivo. Silencing
of FGFR4 expression could weaken the invasive ability, increase the apoptosis
rate, and decrease the proliferation ability of GC cells in vitro and in vivo.
Furthermore, the combination of 5-Fu and BGJ398 had synergy in inhibiting the
proliferation ability and increasing apoptosis rate of GC cells, directing a new
target drug in GC.
PMID- 26432331
TI - Prognostic impact of cytological fluid tumor markers in non-small cell lung
cancer.
AB - The serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), and squamous
cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small
cell lung cancer (NSCLC). Cytologic tumor markers obtained during needle
aspiration biopsies (NAB) of lung lesions are useful for NSCLC diagnosis. This
study investigated the incremental prognostic value of cytologic tumor markers
compared to serum tumor markers. This prospective study included 253 patients
diagnosed with NSCLC by NAB with cytologic tumor marker analysis. Levels of
cytologic CYFRA 21-1, CEA, SCCA, and their serum counterparts were followed up
for survival analysis. Optimal cutoff values for each tumor marker were obtained
for overall survival (OS) and progression-free survival (PFS) analyses. All
patients were followed up for a median of 22.8 months. Using cutoff values of
0.44 ng/ml for C-SCCA, 2.0 ng/ml for S-SCCA, and 3.3 ng/ml for S-CYFRA, a
multivariate analysis revealed that high S-SCCA (hazard ratio, HR, 1.84) and high
C-SCCA (HR, 1.63) were independent predictive factors of OS. The 3-year overall
survival rate was 55 vs. 80 % for high and low C-SCCA, respectively. Cytologic
tumor marker level detection is easily obtainable and provides prognostic
information for NSCLC. Cytologic tumor markers provide comparable prognostic
information relative to serum tumor markers, with C-SCCA acting as a strong
prognostic factor of overall survival and PFS.
PMID- 26432332
TI - MicroRNA-92a promotes growth, metastasis, and chemoresistance in non-small cell
lung cancer cells by targeting PTEN.
AB - MicroRNA-92a (miR-92a) has been reported to play important roles in tumorigenesis
of human various cancers. However, the roles and underlying molecular mechanism
of miR-92a in non-small cell lung cancer (NSCLC) have not been totally
elucidated. Therefore, the aims of this study were to determine the role of miR
92a and to elucidate its regulatory mechanism in NSCLC. We found that miR-92a was
significantly upregulated in NSCLC tissues compared to matched adjacent normal
lung tissues, and its expression is significantly associated with clinical
characteristics of patients, including tumor, node, and metastasis (TNM) stage;
tumor size; and lymph node metastasis (all P < 0.01). Function assays
demonstrated that upregulation of miR-92a in NSCLC cells promoted cell
proliferation, migration, and invasion, decreased apoptosis and caspase-3
activity, and enhanced chemoresistance of NSCLC cells, whereas downregulation of
miR-92a showed the opposite effects. Moreover, phosphatase and tensin homolog
(PTEN), a unique tumor suppressor gene, was confirmed as a direct target of miR
92a, and PTEN messenger RNA (mRNA) expression was decreased in NSCLC tissues and
was inversely correlated with miR-92a. Downregulation of PTEN could mimic the
same effects of miR-92a mimic in NSCLC cells and rescue the effects on NSCLC
cells induced by miR-92a inhibitor. Taken together, these findings suggested that
miR-92a could promote growth, metastasis, and chemoresistance in NSCLC cells at
least partially by targeting PTEN.
PMID- 26432333
TI - Exosomes from adriamycin-resistant breast cancer cells transmit drug resistance
partly by delivering miR-222.
AB - Breast cancer (BCa) is one of the major deadly cancers in women. However,
treatment of BCa is still hindered by the acquired-drug resistance. It is
increasingly reported that exosomes take part in the development, metastasis, and
drug resistance of BCa. However, the specific role of exosomes in drug resistance
of BCa is poorly understood. In this study, we investigate whether exosomes
transmit drug resistance through delivering miR-222. We established an adriamycin
resistant variant of Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line
(MCF-7/Adr) from a drug-sensitive variant (MCF-7/S). Exosomes were isolated from
cell supernatant by ultracentrifugation. Cell viability was assessed by MTT assay
and apoptosis assay. Individual miR-222 molecules in BCa cells were detected by
fluorescence in situ hybridization (FISH). Then, FISH was combined with locked
nucleic acid probes and enzyme-labeled fluorescence (LNA-ELF-FISH). Individual
miR-222 could be detected as bright photostable fluorescent spots and then the
quantity of miR-222 per cell could be counted. Stained exosomes were taken in by
the receipt cells. MCF-7/S acquired drug resistance after co-culture with
exosomes from MCF-7/Adr (A/exo) but did not after co-culture with exosomes from
MCF-7/S (S/exo). The quantity of miR-222 in A/exo-treated MCF-7/S was
significantly greater than in S/exo-treated MCF-7/S. MCF-7/S transfected with miR
222 mimics acquired adriamycin resistance while MCF-7/S transfected with miR-222
inhibitors lost resistance. In conclusion, exosomes are effective in transmitting
drug resistance and the delivery of miR-222 via exosomes may be a mechanism.
PMID- 26432334
TI - Note of the methodological flaws in the paper entitled "Association between the
G870A polymorphism of cyclin D1 gene and glioma risk".
PMID- 26432335
TI - Enantiomeric CopA3 dimer peptide suppresses cell viability and tumor xenograft
growth of human gastric cancer cells.
AB - The CopA3 dimer peptide is a coprisin analog that has an anticancer effect
against human cancer cells in vitro. In this study, we investigated the
anticancer activity of the enantiomeric CopA3 dimer peptide in human gastric
cancer cell lines as well as in an in vivo tumor xenograft model. Enantiomeric
CopA3 reduced gastric cancer cell viability and exhibited cytotoxicity against
cancer cells. Enantiomeric CopA3-induced cell death was mediated by specific
interactions with phosphatidylserine and phosphatidylcholine, membrane components
that are enriched in cancer cells, in a calcein leakage assay. Moreover, acridine
orange/ethidium bromide staining, flow cytometric analysis, and Western blot
analysis showed that enantiomeric CopA3 induced apoptotic and necrotic gastric
cancer cell death. The antitumor effect was also observed in a mouse tumor
xenograft model in which intratumoral inoculation of the peptide resulted in a
significant decrease in the SNU-668 gastric cancer tumor volume. In addition,
periodic acid-Schiff and hematoxylin staining and terminal deoxynucleotidyl
transferase-mediated dUTP nick end labeling (TUNEL) assay revealed apoptotic and
necrotic cell death in tumor masses treated with greater than 150 MUg CopA3.
Collectively, these results indicate that the enantiomeric CopA3 dimer peptide
induces apoptosis and necrosis of gastric cancer cells in vitro and in vivo,
indicating that the peptide is a potential candidate for the treatment of gastric
cancer, which is a common cause of cancer and cancer deaths worldwide.
PMID- 26432336
TI - Recovery patterns, histological observations and genetic integrity in Malus shoot
tips cryopreserved using droplet-vitrification and encapsulation-dehydration
procedures.
AB - A droplet-vitrification procedure is described for cryopreservation of Malus
shoot tips. Survival patterns, recovery types, histological observations, and
genetic integrity were compared for Malus shoot tips cryopreserved using this
droplet-vitrification procedure and an encapsulation-dehydration procedure that
was previously reported by us. In both procedures, three types of shoot tip
recovery were observed following cryopreservation: callus formation without shoot
regrowth, leaf formation without shoot regrowth, and shoot regrowth. Three
categories of histological observations were also identified in cross-sections of
shoot tips recovered after cryopreservation using the two cryogenic procedures.
In category 1, almost all of the cells (94-95%) in the apical dome (AD) were
damaged or killed and only some cells (30-32%) in the leaf primordia (LPs)
survived. In category 2, only a few cells (18-20%) in the AD and some cells (30
31%) in the LPs survived. In category 3, majority of the cells (60-62%) in the AD
and some cells (30-33%) in the LPs survived. These data suggest that shoot
regrowth is correlated to the presence of a majority of surviving cells in the AD
after liquid nitrogen exposure. No polymorphic bands were detected by inter
simple sequence repeats or by random amplified polymorphic DNA assessments, and
ploidy levels analyzed by flow cytometry were unchanged when plants recovered
after cryoexposure were compared to controls. The droplet-vitrification procedure
appears to be robust since seven genotypes representing four Malus species and
one hybrid recovered shoots following cryopreservation. Mean shoot regrowth
levels of these seven genotypes were 48% in the droplet-vitrification method,
which were lower than those (61%) in the encapsulation-dehydration procedure
reported in our previous study, suggesting the latter may be preferred for
routine cryobanking applications for Malus shoot tips.
PMID- 26432337
TI - Complete genome sequence of Lactobacillus heilongjiangensis DSM 28069(T): Insight
into its probiotic potential.
AB - Lactobacillus heilongjiangensis DSM 28069(T) is a potential probiotic isolated
from traditional Chinese pickle. Here we report the complete genome sequence of
this strain. The complete genome is 2,790,548bp with the GC content of 37.5% and
devoid of plasmids. Sets of genes involved in the biosynthesis of riboflavin and
folate were identified in the genome, which revealed its potential application in
biotechnological industry. The genome sequence of L. heilongjiangensis DSM
28069(T) now provides the fundamental information for future studies.
PMID- 26432338
TI - Construction and immunological evaluation of recombinant Lactobacillus plantarum
expressing HN of Newcastle disease virus and DC- targeting peptide fusion
protein.
AB - Newcastle disease virus (NDV) has been considered as one of the most severe
threats to poultry industry. In this study, we constructed a series of food grade
recombinant Lactobacillus plantarum (L. plantarum) strains (RLP) synthesizing
either virus hemagglutinin-neuraminidase protein (HN) alone or HN fused with DC
cells targeting peptides (DCpep), named RLP(pSIP409-HN) and RLP (pSIP409-HN
DCpep), respectively. The immune responses and protective efficacy were then
evaluated in chickens. Results showed that the presence of DCpep in RLP (pSIP409
HN-DCpep) group significantly increased the production of secretory
immunoglobulin A (SIgA) in intestines and the percentages of CD3(+)CD4(+) T cells
in spleen and peripheral blood leukocytes (P<0.05) compared to chickens immunized
with RLP (pSIP409-HN). In addition, the similar enhancement effects were also
observed with regard to trachea SIgA, T lymphocytes proliferation and survival
rates after NDV challenge, even without significant statics differences. The
results demonstrated the possibility to take use of DCpep as an immune adjuvant
in the design of NDV vaccine.
PMID- 26432339
TI - DNA microarray analysis of the cyanotroph Pseudomonas pseudoalcaligenes CECT5344
in response to nitrogen starvation, cyanide and a jewelry wastewater.
AB - Pseudomonas pseudoalcaligenes CECT5344 is an alkaliphilic bacterium that can use
cyanide as nitrogen source for growth, becoming a suitable candidate to be
applied in biological treatment of cyanide-containing wastewaters. The assessment
of the whole genome sequence of the strain CECT5344 has allowed the generation of
DNA microarrays to analyze the response to different nitrogen sources. The mRNA
of P. pseudoalcaligenes CECT5344 cells grown under nitrogen limiting conditions
showed considerable changes when compared against the transcripts from cells
grown with ammonium; up-regulated genes were, among others, the glnK gene
encoding the nitrogen regulatory protein PII, the two-component ntrBC system
involved in global nitrogen regulation, and the ammonium transporter-encoding
amtB gene. The protein coding transcripts of P. pseudoalcaligenes CECT5344 cells
grown with sodium cyanide or an industrial jewelry wastewater that contains high
concentration of cyanide and metals like iron, copper and zinc, were also
compared against the transcripts of cells grown with ammonium as nitrogen source.
This analysis revealed the induction by cyanide and the cyanide-rich wastewater
of four nitrilase-encoding genes, including the nitC gene that is essential for
cyanide assimilation, the cyanase cynS gene involved in cyanate assimilation, the
cioAB genes required for the cyanide-insensitive respiration, and the ahpC gene
coding for an alkyl-hydroperoxide reductase that could be related with iron
homeostasis and oxidative stress. The nitC and cynS genes were also induced in
cells grown under nitrogen starvation conditions. In cells grown with the jewelry
wastewater, a malate quinone:oxidoreductase mqoB gene and several genes coding
for metal extrusion systems were specifically induced.
PMID- 26432340
TI - Seasonality in physical activity and walking of healthy older adults.
AB - BACKGROUND: An increasing number of older adults require improvements in their
quality of life. Physical activities, particularly walking ability, are of
primary importance for older adults. The influence of season on physical activity
has not been sufficiently studied among older adults. Therefore, this report
compared the physical activity and walking of older individuals between summer
and winter seasons using a longitudinal study design in a community in a mid
latitude area. METHODS: Participants in the study comprised 39 healthy community
dwelling adults ranging in age from 65 to 80 years. Physical parameters and
activities as well as the preferred speed of walking were measured at half-year
intervals. RESULTS: Significant seasonal differences from summer to winter and
from winter to summer were detected. Specifically, body fat percentage, single
leg stance, walking speed, cadence, stride length, and trunk and head-trunk pitch
ranges were greater in winter than in summer, whereas grip strength and steps per
day were greater in summer. Temperature and total activity level were considered
to be related to body fat percentage. Grip strength was thought to be affected by
outdoor temperature. The possibility of relationships between increased activity
per unit time in older adults and increased preferred walking speed, cadence, and
stride length in winter temperatures was discussed. CONCLUSION: The seasonal
climatic environment of the geographic area of this study affected the activity
level of the participants. These results indicate that seasonality should be
considered when analyzing physical activity and walking in older adults.
PMID- 26432342
TI - Event-related potentials indicate that fluency can be interpreted as familiarity.
AB - Recent evidence suggests that fluency may be capable of supporting recognition
independently of familiarity. This hypothesis was further tested in the present
study. 29 participants encoded name-brand and off-brand products in an incidental
task. Participants then judged whether the product was old or new during two
tests with products from one category (i.e., only name-brand or only off-brand
products) and a mixed test (where both name-brand and off-brand products were
shown). The ERP data elicited by off-brand products varied as a function of test
format. During the mixed test, off-brand products were correlated with a FN400
effect, whereas a fluency ERP (old ERPs were more negative than new at parietal
electrodes 225-400ms) was observed during the other test. Importantly, no FN400
was detected during this test. The ERP results suggest that viewing the off-brand
products during the mixed test produced a familiarity experience; however,
fluency supported recognition when viewing off-brand products on the other test.
The results are strong evidence that top-down processing of visual features
during recognition interprets the information relative to the context. This
process results in either fluency or, in other contexts, it is interpreted as
familiarity as the Discrepancy-Attribution Hypothesis (Whittlesea and Williams,
2001a, 2001b) contends.
PMID- 26432341
TI - An investigation of care-based vs. rule-based morality in frontotemporal
dementia, Alzheimer's disease, and healthy controls.
AB - Behavioral changes in dementia, especially behavioral variant frontotemporal
dementia (bvFTD), may result in alterations in moral reasoning. Investigators
have not clarified whether these alterations reflect differential impairment of
care-based vs. rule-based moral behavior. This study investigated 18 bvFTD
patients, 22 early onset Alzheimer's disease (eAD) patients, and 20 healthy age
matched controls on care-based and rule-based items from the Moral Behavioral
Inventory and the Social Norms Questionnaire, neuropsychological measures, and
magnetic resonance imaging (MRI) regions of interest. There were significant
group differences with the bvFTD patients rating care-based morality
transgressions less severely than the eAD group and rule-based moral behavioral
transgressions more severely than controls. Across groups, higher care-based
morality ratings correlated with phonemic fluency on neuropsychological tests,
whereas higher rule-based morality ratings correlated with increased difficulty
set-shifting and learning new rules to tasks. On neuroimaging, severe care-based
reasoning correlated with cortical volume in right anterior temporal lobe, and
rule-based reasoning correlated with decreased cortical volume in the right
orbitofrontal cortex. Together, these findings suggest that frontotemporal
disease decreases care-based morality and facilitates rule-based morality
possibly from disturbed contextual abstraction and set-shifting. Future research
can examine whether frontal lobe disorders and bvFTD result in a shift from
empathic morality to the strong adherence to conventional rules.
PMID- 26432344
TI - Water purifier cannot claim to be endorsed by doctors, India's advertising
regulator says.
PMID- 26432343
TI - Intact action segmentation in Parkinson's disease: Hypothesis testing using a
novel computational approach.
AB - Action observation is known to trigger predictions of the ongoing course of
action and thus considered a hallmark example for predictive perception. A
related task, which explicitly taps into the ability to predict actions based on
their internal representations, is action segmentation; the task requires
participants to demarcate where one action step is completed and another one
begins. It thus benefits from a temporally precise prediction of the current
action. Formation and exploitation of these temporal predictions of external
events is now closely associated with a network including the basal ganglia and
prefrontal cortex. Because decline of dopaminergic innervation leads to impaired
function of the basal ganglia and prefrontal cortex in Parkinson's disease (PD),
we hypothesised that PD patients would show increased temporal variability in the
action segmentation task, especially under medication withdrawal (hypothesis 1).
Another crucial aspect of action segmentation is its reliance on a semantic
representation of actions. There is no evidence to suggest that action
representations are substantially altered, or cannot be accessed, in non-demented
PD patients. We therefore expected action segmentation judgments to follow the
same overall patterns in PD patients and healthy controls (hypothesis 2),
resulting in comparable segmentation profiles. Both hypotheses were tested with a
novel classification approach. We present evidence for both hypotheses in the
present study: classifier performance was slightly decreased when it was tested
for its ability to predict the identity of movies segmented by PD patients, and a
measure of normativity of response behaviour was decreased when patients
segmented movies under medication-withdrawal without access to an episodic memory
of the sequence. This pattern of results is consistent with hypothesis 1.
However, the classifier analysis also revealed that responses given by patients
and controls create very similar action-specific patterns, thus delivering
evidence in favour hypothesis 2. In terms of methodology, the use of classifiers
in the present study allowed us to establish similarity of behaviour across
groups (hypothesis 2). The approach opens up a new avenue that standard
statistical methods often fail to provide and is discussed in terms of its merits
to measure hypothesised similarities across study populations.
PMID- 26432345
TI - Medicaid and Women's Health Coverage Two Years into the Affordable Care Act.
PMID- 26432347
TI - Pressure limited vesico-amniotic shunt allows normal lung growth in a fetal lamb
model of obstructive uropathy.
AB - BACKGROUND: In our fetal lamb model of lower urinary tract obstruction, a
pressure limited shunt preserves bladder function and renal development. This
study investigates the effects on pulmonary histology. METHODS: We created
obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra
and urachus, and delivering them at term (130-145days). We compared pulmonary
histology in 4 groups: group A, OU without shunt; group B, pressure limited
shunt; group C, non-valved shunt. Shunts were inserted 3weeks post-obstruction.
Group D were normal controls. RESULTS: We compared 27 fetuses: 7 fetuses in group
A, 4 fetuses in group B, 2 fetuses in group C, and 14 fetuses in group D. There
was no significant difference in lung volume in any group. In group A, there were
some areas of atelectasis and incomplete alveolar formation histologically. The
alveoli in group A lambs lungs had a predominance of type II cells, whereas group
B lambs lungs were lined by type I epithelial cells and were essentially
indistinguishable from controls. CONCLUSIONS: This study suggests that using a
pressure-limited vesico-amniotic shunt in OU may preserve the renal tract and the
lungs.
PMID- 26432346
TI - Prospective Analysis of Health and Mortality Risk in Veteran and Non-Veteran
Participants in the Women's Health Initiative.
AB - BACKGROUND: The health of postmenopausal women veterans is a neglected area of
study. A stronger empirical evidence base is needed, and would inform the
provision of health care for the nearly 1 million U.S. women veterans currently
50 years of age or older. To this end, the present work compares salient health
outcomes and risk of all-cause mortality among veteran and non-veteran
participants of the Women's Health Initiative (WHI). METHODS: This study features
prospective analysis of long-term health outcomes and mortality risk (average
follow-up, 8 years) among the 3,706 women veterans and 141,009 non-veterans who
participated in the WHI Observational Study or Clinical Trials. Outcome
measurements included confirmed incident cases of cardiovascular disease (CVD),
cancer, diabetes, hip fractures, and all-cause mortality. RESULTS: We identified
17,968 cases of CVD, 19,152 cases of cancer, 18,718 cases of diabetes, 2,817
cases of hip fracture, and 13,747 deaths. In Cox regression models adjusted for
age, sociodemographic variables, and health risk factors, veteran status was
associated with significantly increased risk of all-cause mortality (hazard ratio
[HR], 1.13; 95% CI, 1.03-1.23), but not with risk of CVD (HR, 1.00; 95% CI, 0.90
1.11), cancer (HR, 1.04; 95% CI, 0.95-1.14), hip fracture (HR, 1.16; 95% CI, 0.94
1.43), or diabetes (HR, 1.00; 95% CI, 0.89-1.1). CONCLUSIONS: Women veterans'
postmenopausal health, particularly risk for all-cause mortality, warrants
further consideration. In particular, efforts to identify and address modifiable
risk factors associated with all-cause mortality are needed.
PMID- 26432348
TI - Adverse effects of perinatal nicotine exposure on reproductive outcomes.
AB - Nicotine exposure during pregnancy through cigarette smoking, nicotine
replacement therapies or e-cigarette use continues to be a widespread public
health problem, impacting both fetal and postnatal health. Yet, at this time,
there remains limited data regarding the safety and efficacy in using these
nicotine products during pregnancy. Notably, reports assessing the effect of
nicotine exposure on postnatal health outcomes in humans, including reproductive
health, are severely lacking. Our current understanding regarding the
consequences of nicotine exposure during pregnancy is limited to a few animal
studies, which do not comprehensively address the underlying cellular mechanisms
involved. This paper aims to critically review the current knowledge from human
and animal studies regarding the direct and indirect effects (e.g. obesity) of
maternal nicotine exposure, regardless of its source, on reproductive outcomes in
pregnancy and postnatal life. Furthermore, this review highlights several key
cellular mechanisms involved in these adverse reproductive deficits including
oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. By
understanding the interplay of the cellular mechanisms involved, further
strategies could be developed to prevent the reproductive abnormalities resulting
from exposure to nicotine in utero and influence informed clinical guidelines for
pregnant women.
PMID- 26432349
TI - Estradiol promotes cells invasion by activating beta-catenin signaling pathway in
endometriosis.
AB - Endometriosis is an estrogen-dependent disease that involves the adhesion,
invasion, and angiogenesis of endometrial tissues outside of the uterine cavity.
We hypothesized that a link exists between estrogen and beta-catenin (beta
catenin) signaling in the pathogenesis of endometriosis. Human endometrial
stromal cells (HESCs) were separated from eutopic endometrial tissues that were
obtained from patients with endometriosis. beta-catenin expression and cells
invasiveness ability were up-regulated by 17beta-estradiol (E2) in an estrogen
receptor (ESR)-dependent manner, whereas beta-catenin siRNA abrogated this
phenomenon. Moreover, co-immunoprecipitation and dual immunofluorescence studies
confirmed ESR1, beta-catenin, and lymphoid enhancer factor 1/T cell factor 3 co
localization in the nucleus in HESCs after E2 treatment. To determine the role of
beta-catenin signaling in the implantation of ectopic endometrium, we
xenotransplanted eutopic endometrium from endometriosis patients into
ovariectomized severe combined immunodeficiency mice. The implantation of the
endometrium was suppressed by beta-catenin siRNA. Collectively, studies regarding
beta-catenin signaling are critical for improving our understanding of the
pathogenesis of estrogen-induced endometriosis, which can translate into the
development of treatments and therapeutic strategies for endometriosis.
PMID- 26432350
TI - Role of cysteine-58 and cysteine-95 residues in the thiol di-sulfide
oxidoreductase activity of Macrophage Migration Inhibitory Factor-2 of Wuchereria
bancrofti.
AB - Macrophage Migration Inhibitory Factor (MIF) is the first human cytokine reported
and was thought to have a central role in the regulation of inflammatory
responses. Homologs of this molecule have been reported in bacteria,
invertebrates and plants. Apart from cytokine activity, it also has two catalytic
activities viz., tautomerase and di-sulfide oxidoreductase, which appear to be
involved in immunological functions. The CXXC catalytic site is responsible for
di-sulfide oxidoreductase activity of MIF. We have recently reported thiol
disulfide oxidoreductase activity of Macrophage Migration Inhibitory Factor-2 of
Wuchereria bancrofti (Wba-MIF-2), although it lacks the CXXC motif. We
hypothesized that three conserved cysteine residues might be involved in the
formation of di-sulfide oxidoreductase catalytic site. Homology modeling of Wba
MIF-2 showed that among the three cysteine residues, Cys58 and Cys95 residues
came in close proximity (3.23A) in the tertiary structure with pKa value 9,
indicating that these residues might play a role in the di-sulfide oxidoreductase
catalytic activity. We carried out site directed mutagenesis of these residues
(Cys58Ser & Cys95Ser) and expressed mutant proteins in Escherichia coli. The
mutant proteins did not show any oxidoreductase activity in the insulin reduction
assay, thus indicating that these two cysteine residues are vital for the
catalytic activity of Wba-MIF-2.
PMID- 26432351
TI - Medicinal plants of the genus Anthocleista--A review of their ethnobotany,
phytochemistry and pharmacology.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: The genus Anthocleista of the Gentianaceae family
contains 14 species of trees and shrub-like plants distributed in tropical
Africa, in Madagascar and on the Comoros. Traditionally, they are commonly used
in the treatment of diabetes, hypertension, malaria, typhoid fever, obesity,
diarrhea, dysentery, hyperprolactinemia, abdominal pain, ulcer, jaundice, asthma,
hemorrhoids, hernia, cancer, wounds, chest pains, inflammations, rheumatism,
STDs, infertility and skin diseases. They serve as an anthelmintic, laxative,
diuretic and contraceptive. This review aims to provide for the first time a
repository of ethnopharmacological information while critically evaluating the
relation between the traditional medicinal uses, chemical constituents and
pharmacological activities of the Anthocleista species so as to unveil
opportunities for future research. MATERIALS AND METHODS: A search for relevant
information on Anthocleista species was performed on scientific databases
(Pubmed, Google Scholar, SciFinder, Web of Science, Scopus, PubChem and other web
sources such as The Plant List, Kew Botanical Garden and PROTA) and books, PhD
and MSc dissertations for un-published resources. RESULTS: Out of the 14 species
of Anthocleista, 6 have been reported in literature to be widely used in
traditional medicine for the treatment of various ailments. The six species
include: A. djalonensis, A. vogelii, A. nobilis, A. grandiflora, A.
schweinfurthii, and A. liebrechtsiana. The chemical compounds isolated from
Anthocleista species fall into the class of phytochemicals such as secoiridoids,
nor-secoiridoids, xanthones, phytosterols, triterpenes, alkaloids, and others of
which majority of the compounds were isolated from A. djalonensis and A. vogelii.
The in vitro and in vivo pharmacological studies on the crude extracts, fractions
and few isolated compounds of Anthocleista species showed antidiabetic,
antiplasmodial, antimicrobial, hypotensive, spasmogenic, anti-obesity,
antiulcerogenic, analgesic, anti-inflammatory, antioxidant, antitrypanosomal,
anthelmintic, fertility, diuretic and laxative activities which supports most of
their uses in traditional medicine. However, the bulk of the studies where
centered on the antidiabetic, antiplasmodial and antimicrobial activities of
Anthocleista species, although the evidence of its antiplasmodial effect was not
convincing enough due to the discrepancies between the in vitro and in vivo
results. CONCLUSION: A. djalonensis and A. vogelii are potential antidiabetic and
antibacterial agents. The antibacterial potency relates to infections or diseases
caused by E. coli, S. typhi and S. aureus such as urinary tract infections,
typhoid, diarrhea, skin diseases, and food poisoning. Pharmacological research on
this genus is quite elementary and limited, thus, more advanced research is
necessary to isolate and determine the activities of bioactive compounds in vitro
and in vivo, establish their mechanisms of action and commence the process of
clinical research.
PMID- 26432352
TI - Central European medicinal bryophytes in the 16th-century work by Caspar
Schwenckfeld, and their ethnopharmacological origin.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ubiquitous bryophyte species are reported from
European, American and Asian ethnopharmacies. Some of their traditional medicinal
uses are similar in distant and isolated cultures, and moreover, medicinal
properties of some bryophytes are currently confirmed as justified by their
chemical constituents. Aims of the work: we identify bryophytes listed in a
medicinal and botanical work from 1600, and compare their medicinal applications
(known in Europe between 1530-1600) with other ethnopharmacological data about
these species and with modern pharmacological knowledge. This way we attempt to
display origins of medicinal usage of bryophytes in Central Europe. MATERIALS AND
METHODS: Bryophyte species in bibliographical sources printed in Central Europe
(starting from O. Brunfels' Herbarum vivae Eicones... Argentorati, 1530) were
identified according to old and recent taxonomical references. Caspar
Schwenckfeld's scientific output from 1600 was treated here as a summary of 16th
century knowledge about medicinal bryophytes. RESULTS: Central European pharmacy
about the year 1600 was familiar with the following bryophytes: Marchantia
polymorpha L., Polytrichum commune Hedw., P. formosum Hedw. and Funaria
hygrometrica Hedw. CONCLUSIONS: Between 1530-1600 in Central Europe the number of
medicinal bryophytes increased from 2 (Lichen sive Hepatica and Polytrichon) to
4. Pharmaceutical usage of them was similar as in other, distant ethnopharmacies.
Further 2-4 mosses (Rhytidiadelphus loreus and Rh. squarrosus; Thuidium
tamariscinum and Th. delicatulum) were recognised as non-medicinal.
PMID- 26432353
TI - Text mining for pharmacovigilance: Using machine learning for drug name
recognition and drug-drug interaction extraction and classification.
AB - Pharmacovigilance (PV) is defined by the World Health Organization as the science
and activities related to the detection, assessment, understanding and prevention
of adverse effects or any other drug-related problem. An essential aspect in PV
is to acquire knowledge about Drug-Drug Interactions (DDIs). The shared tasks on
DDI-Extraction organized in 2011 and 2013 have pointed out the importance of this
issue and provided benchmarks for: Drug Name Recognition, DDI extraction and DDI
classification. In this paper, we present our text mining systems for these tasks
and evaluate their results on the DDI-Extraction benchmarks. Our systems rely on
machine learning techniques using both feature-based and kernel-based methods.
The obtained results for drug name recognition are encouraging. For DDI
Extraction, our hybrid system combining a feature-based method and a kernel-based
method was ranked second in the DDI-Extraction-2011 challenge, and our two-step
system for DDI detection and classification was ranked first in the DDI
Extraction-2013 task at SemEval. We discuss our methods and results and give
pointers to future work.
PMID- 26432354
TI - Exploring methods for identifying related patient safety events using structured
and unstructured data.
AB - Most healthcare systems have implemented patient safety event reporting systems
to identify safety hazards. Searching the safety event data to find related
patient safety reports and identify trends is challenging given the complexity
and quantity of these reports. Structured data elements selected by the event
reporter may be inaccurate and the free-text narrative descriptions are difficult
to analyze. In this paper we present and explore methods for utilizing both the
unstructured free-text and structured data elements in safety event reports to
identify and rank similar events. We evaluate the results of three different free
text search methods, including a unique topic modeling adaptation, and structured
element weights, using a patient fall use case. The various search techniques and
weight combinations tended to prioritize different aspects of the event reports
leading to different search and ranking results. These search and prioritization
methods have the potential to greatly improve patient safety officers, and other
healthcare workers, understanding of which safety event reports are related.
PMID- 26432355
TI - A context-aware approach for progression tracking of medical concepts in
electronic medical records.
AB - Electronic medical records (EMRs) for diabetic patients contain information about
heart disease risk factors such as high blood pressure, cholesterol levels, and
smoking status. Discovering the described risk factors and tracking their
progression over time may support medical personnel in making clinical decisions,
as well as facilitate data modeling and biomedical research. Such highly patient
specific knowledge is essential to driving the advancement of evidence-based
practice, and can also help improve personalized medicine and care. One general
approach for tracking the progression of diseases and their risk factors
described in EMRs is to first recognize all temporal expressions, and then assign
each of them to the nearest target medical concept. However, this method may not
always provide the correct associations. In light of this, this work introduces a
context-aware approach to assign the time attributes of the recognized risk
factors by reconstructing contexts that contain more reliable temporal
expressions. The evaluation results on the i2b2 test set demonstrate the efficacy
of the proposed approach, which achieved an F-score of 0.897. To boost the
approach's ability to process unstructured clinical text and to allow for the
reproduction of the demonstrated results, a set of developed .NET libraries used
to develop the system is available at
https://sites.google.com/site/hongjiedai/projects/nttmuclinicalnet.
PMID- 26432357
TI - The Human Vocal Fold Layers. Their Delineation Inside Vocal Fold as a Background
to Create 3D Digital and Synthetic Glottal Model.
AB - OBJECTIVES: To distinguish the layers of the vocal fold at the submacroscopic
level and determine their boundaries, thereby creating a basis for the
construction of a digital 3D model of the human vocal folds. STUDY DESIGN: The
submacroscopic delineation of individual layers of fixed vocal ligaments based on
their structural differences. METHODS: Following tasks were performed: (1)
Submicroscopic dissection of the vocal folds fixed in a solution with a low
concentration of fixation substance (in this case, the muscular parts of the
vocal folds were removed); (2) Using the CT and micro-MRI methods, we determined
the position of the dense parts of the vocal folds; and (3) Using a modified
plastination method, we preserved macroscopically natural appearance of all
ligamentous and muscular layers. RESULTS: The vocal ligament is composed of
several volumes of connective tissue. It is surrounded by layers of fibrous
material permeated by liquid. Individual fibers stretch all the way to the
fibrous casing (fascia) of the vocal muscle. The vocal fold layer surrounding the
ligament externally has a stratified character. CONCLUSIONS: According to our
findings, we infer that this ligament is a complex of several fibrous bundles
which are surrounded by a thin layer of connective tissue. Below the surface of
epithelium of the vocal fold run several separate bands which are closely
adjacent to it. Therefore, we propose using the term ligamentous complex
involving closely adjacent structures, instead of the vocal ligament only. We
feel that it better reflects the functional and structural character of the whole
formation.
PMID- 26432356
TI - Renal proximal tubule Na,K-ATPase is controlled by CREB-regulated transcriptional
coactivators as well as salt-inducible kinase 1.
AB - Sodium reabsorption by the kidney is regulated by locally produced natriuretic
and anti-natriuretic factors, including dopamine and norepinephrine,
respectively. Previous studies indicated that signaling events initiated by these
natriuretic and anti-natriuretic factors achieve their effects by altering the
phosphorylation of Na,K-ATPase in the renal proximal tubule, and that protein
kinase A (PKA) and calcium-mediated signaling pathways are involved. The same
signaling pathways also control the transcription of the Na,K-ATPase beta subunit
gene atp1b1 in renal proximal tubule cells. In this report, evidence is presented
that (1) both the recently discovered cAMP-regulated transcriptional coactivators
(CRTCs) and salt-inducible kinase 1 (SIK1) contribute to the transcriptional
regulation of atp1b1 in renal proximal tubule (RPT) cells and (2) renal
effectors, including norepinephrine, dopamine, prostaglandins, and sodium, play a
role. Exogenously expressed CRTCs stimulate atp1b1 transcription. Evidence for a
role of endogenous CRTCs includes the loss of transcriptional regulation of
atp1b1 by a dominant-negative CRTC, as well as by a CREB mutant, with an altered
CRTC binding site. In a number of experimental systems, SIK phosphorylates CRTCs,
which are then sequestered in the cytoplasm, preventing their nuclear effects.
Consistent with such a role of SIK in primary RPT cells, atp1b1 transcription
increased in the presence of a dominant-negative SIK1, and in addition,
regulation by dopamine, norepinephrine, and monensin was disrupted by a dominant
negative SIK1. These latter observations can be explained if SIK1 is
phosphorylated and inactivated in the presence of these renal effectors. Our
results support the hypothesis that Na,K-ATPase in the renal proximal tubule is
regulated at the transcriptional level via SIK1 and CRTCs by renal effectors, in
addition to the previously reported control of the phosphorylation of Na,K
ATPase.
PMID- 26432358
TI - Estrogen suppresses breast cancer proliferation through GPER / p38 MAPK axis
during hypoxia.
AB - Breast cancer cells frequently experience hypoxia which is associated with
resistance to hormonal therapy and poor clinical prognosis, making it important
to understand the function of estrogen under hypoxic condition. Here, we
demonstrate that estrogen suppresses breast cancer cell growth under hypoxia,
through inhibition at G1/S phase of cell cycle, by elevation of p21 expression.
The involvement of GPER in estrogen mediated growth arrest was elucidated using
specific ligands and siRNA. Although, estrogen was observed to activate both
p44/42 and p38 MAPK signaling, pharmacological inhibition and silencing of p38
MAPK abrogated the induction of p21 expression and growth arrest, during hypoxia.
The involvement of estrogen induced ROS in the p38 MAPK mediated p21 expression
and cell growth arrest was established by observing that scavenging of ROS by NAC
abrogated p38 MAPK activation and p21 expression during hypoxia. In conclusion,
Estrogen suppresses breast cancer growth by inhibiting G1/S phase transition
through GPER/ROS/p38 MAPK/p21 mediated signaling during hypoxic condition.
PMID- 26432359
TI - Breast conservative surgery and local recurrence.
AB - INTRODUCTION: Breast conservation is a legacy of Umberto Veronesi who laid the
groundwork for the preservation of the body image of women affected by breast
cancer (BC) with the Milan I study in the late 70ies of the last millennium.
Breast conservative surgery (BCS) has two aspects: oncological safety of tumour
resection with free margins and aesthetic preservation of the breast.
Determinants of local control used to be T-size, nodal status and receptor status
until biologically driven concepts defined risk of recurrence on the basis of
molecular portraits. We explored whether these concepts of intrinsic subtypes
prove at a large scale in the context of BCS and which surgical techniques
procure best oncological and aesthetic outcomes, avoiding re-excision and
necessity of conversion to mastectomy. PATIENTS AND METHODS: We analyzed 1035 BCS
patients with primary unilateral breast cancer (2004-2009) with regards to the
local recurrence as a function of tumour location, surgical technique, resection
volume, T-size, nodal status, grading, histopathological and intrinsic subtype
and margins. RESULTS: Five surgical techniques were applied to 944 eligible
patients at a median follow-up of 5.2 years with the following frequency:
Glandular rotation mammoplasty (63.8%), tumour-adapted rotation mammoplasty
(20.9%), dermoglandular rotation mammoplasty (6.7%), 4.4% (lateral thoracic wall
advancement), 0.7% latissimus dorsi flap (0.7%) and others (13.5%). Tumour-free
margins were achieved in 88.6% of all patients at first surgery. Recurrence was
independent of the surgical technique used, resection volume, T-size (in a T1/T2
cohort), nodal status (in low N-stages: NO/N1) and histopathology (inv.-ductal
vs. lobular), however non-invasive subtype (DCIS), high grading (G3 vs. G1), non
luminal Her2 positive BC and triple-negative breast cancer (TNBC) were
significantly associated with local recurrence. CONCLUSIONS: Five defined
oncoplastic principles presented in our nomogramme (targeted breast surgery)
allow the reconstruction of major segmental resection defects during breast
conserving therapy with high clinical applicability and result in favorable
oncological and aesthetic outcome. Recurrence was not a function of traditional
prognostic factors like T-size or nodal status (in a T1/T2, N0/N1 cohort), but of
grading, intrinsic subtypes and non-invasive breast cancer components. Lobular
histology, multi-centricity and DCIS were predictive for breast preservation
failure and conversion to mastectomy.
PMID- 26432360
TI - Optimal surgical management for high-risk populations.
AB - The recognition that breast cancer is a group of genetically distinct diseases
with differing responses to treatment and varying patterns of both local and
systemic failure has led to many questions regarding optimal therapy for those
considered to be high risk. Young patients, patients with triple-negative breast
cancer (TNBC), and those who harbor a deleterious mutation in BRCA1 or BRCA2 are
frequently considered to be at highest risk of local failure, leading to
speculation that more-aggressive surgical treatment is warranted in these
patients. For both age and the triple-negative subtype, it appears that the
intrinsic biology which imparts inferior outcomes is not overcome with
mastectomy; therefore, a recommendation for more extensive surgical therapy among
these higher-risk groups is not warranted. For those at inherited risk, a more
aggressive surgical approach may be preferable, however; patient age, ER status,
stage of the index lesion, and individual patient preferences should all be
considered in the surgical decision-making process.
PMID- 26432361
TI - Direct injection human plasma analysis for the quantification of antihypertensive
drugs for therapeutic drug monitoring using hydrophilic interaction liquid
chromatography/electrospray ionization mass spectrometry.
AB - The concept of personalized medicine is related to the development of new
sensitive, precise and accurate analytical methods for therapeutic drug
monitoring. In this article a rapid, sensitive and specific method was developed
for the quantification of aliskiren, losartan, valsartan and hydrochlorothiazide
in human plasma. Sample preparation was performed by protein precipitation with
acetonitrile followed by filtration. All analytes and the internal standard
(tiamulin) were separated by hydrophilic interaction liquid chromatography using
an X-Bridge-HILIC analytical column (150.0*2.1mm i.d., particle size 3.5MUm)
under isocratic elution. The mobile phase was composed of a 10% 5mM ammonium
formate water solution pH 4.5, adjusted with formic acid, in acetonitrile and
pumped at a flow rate of 0.25mLmin(-1). The assay was linear over the
concentration range of 5-500ngmL(-1) for all the analytes. Intermediate precision
was less than 5.2% over the tested concentration ranges. The method is the first
reported application of HILIC in the analysis antihypertensives in human plasma.
With a small sample size (50MUL human plasma) and a run time less than 6.0min for
each sample the method can be used to support a wide range of clinical studies
and therapeutic drug monitoring.
PMID- 26432363
TI - Understanding the dissolution of cellulose in 1-butyl-3-methylimidazolium
acetate+DMAc solvent.
AB - Cellulose solvent ([C4mim][CH3COO]/DMAc) could be obtained by adding N,N
dimethylacetamide (DMAc) in 1-butyl-3-methylimidazolium acetate
([C4mim][CH3COO]). The solubilities of cellulose in [C4mim][CH3COO]/DMAc solvents
were determined at 25 degrees C. The effects of molar ratio of DMAc to
[C4mim][CH3COO] on cellulose solubility and the possible dissolution mechanism of
cellulose in [C4mim][CH3COO]/DMAc solvent have been studied. Moreover, the
regenerated cellulose from [C4mim][CH3COO]/DMAc solvent were characterized by X
ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and
thermogravimetric analysis (TGA). It was found that, cellulose was more readily
dissolved in [C4mim][CH3COO]/DMAc solvent than in a neat [C4mim][CH3COO], which
mainly attributed to the increased "free" [CH3COO](-) anions and [C4mim](+)
cations which result from the dissociation of [C4mim][CH3COO] by DMAc. Moreover,
the regenerated cellulose from [C4mim][CH3COO]/DMAc solvent displayed good
thermostability and similar molecular structure to the original cellulose.
PMID- 26432364
TI - Effect of chemical modification on molecular structure and functional properties
of Musa AAB starch.
AB - Starch extracted from Musa AAB (poovan banana) was subjected to acetylation, acid
thinning and oxidation. The effect of the treatments on molecular structure and
functional properties of starch were analysed. Chemical composition revealed that
non-starch components were reduced after chemical treatment. Amylose content of
starch decreased on acetylation from 24.16% to 20.90%, whereas it increased to
24.50% and 25.5% on oxidation and acid-thinning, respectively. X-ray diffraction
pattern of modified starches showed B-type crystalline structure with peaks at
2theta=5.5 degrees , 15.0 degrees , 17.1 degrees and 23.5 degrees ; which were
parallel with the pattern observed in case of native starch. Swelling capacity of
starch granules was found to reduce by acid-thinning and oxidation but
acetylation induced to increase it. The percentage of colour (L*, a* and b*),
solubility and water absorption capacities varied significantly from native
starch after chemical modification. Changes in gelatinisation temperatures and
enthalpy value of starches were observed in modified starches and it is varied
according to reaction conditions. Pasting properties of the starches was
increased by acetylation and oxidation while acid-thinning reduced it (P<0.05).
PMID- 26432362
TI - The C4 region as a target for HIV entry inhibitors--NMR mapping of the
interacting segments of T20 and gp120.
AB - The peptide T20, which corresponds to a sequence in the C-terminal segment of the
HIV-1 transmembrane glycoprotein gp41, is a strong entry inhibitor of HIV-1. It
has been assumed that T20 inhibits HIV-1 infection by binding to the trimer
formed by the N-terminal helical region (HR1) of gp41, preventing the formation
of a six helix bundle by the N- and C-terminal helical regions of gp41. In
addition to binding to gp41, T20 was found to bind to gp120 of X4 viruses and
this binding was suggested to be responsible for an alternative mechanism of HIV
1 inhibition by this peptide. In the present study, T20 also was found to bind R5
gp120. Using NMR spectroscopy, the segments of T20 that interact with both gp120
and a gp120/CD4M33 complex were mapped. A peptide corresponding to the fourth
constant region of gp120, sC4, was found to partially recapitulate gp120 binding
to T20 and the segment of this peptide interacting with T20 was mapped. The
present study concludes that an amphiphilic helix on the T20 C-terminus binds
through mostly hydrophobic interactions to a nonpolar gp120 surface formed
primarily by the C4 region. The ten- to thousand-fold difference between the EC50
of T20 against viral fusion and the affinity of T20 to gp120 implies that binding
to gp120 is not a major factor in T20 inhibition of HIV-1 fusion. Nevertheless,
this hydrophobic gp120 surface could be a target for anti-HIV therapeutics.
PMID- 26432365
TI - Development of grafted xyloglucan micelles for pulmonary delivery of curcumin: In
vitro and in vivo studies.
AB - A novel grafted copolymer consisting of l-lactide grafted xyloglucan was
synthesized by polymerization reaction and characterized. The grafted copolymers
were analyzed by Fourier-transform infrared spectrometry (FTIR) and (1)H nuclear
magnetic resonance ((1)H NMR) was performed to confirm the grafting of l-poly
lactic acid on xyloglucan. The grafted polymer forms micelles at the critical
micelle concentration of 0.0150 wt% with the average particle size of 102 nm, as
determined by particle size analyzer. The zeta potential of the curcumin loaded
micelles was -18.2 mV, an acceptable drug loading efficiency of 68.9 +/- 0.02%
and the entrapment efficiency of 96.38 +/- 0.2%. The release study for 5h showed
a sustained release property. In vitro assessment demonstrates suitability of
micelles as dry powder for inhalation. In vivo studies showed significant
improvement in bioavailability on pulmonary administration of curcumin micelles
as DPI formulation. The potential for pulmonary delivery curcumin loaded in
micelles was evaluated. In conclusion, polymeric micelle based on a newly
synthesized grafted xyloglucan could be suitable carrier for pulmonary delivery
of curcumin.
PMID- 26432367
TI - Purification and antibiofilm activity of AHL-lactonase from endophytic
Enterobacter aerogenes VT66.
AB - The opportunistic pathogen Pseudomonas aeruginosa uses biofilm lifestyle to
resist antibiotic treatment. In our study, endophytic bacterium Enterobacter
aerogenes VT66 quenched the N-acyl homoserine lactone (AHL) molecules produced by
P. aeruginosa PAO1. The quorum quenching activity was attributed to the presence
of AHL-lactonase. The AHL-lactonase was purified using column chromatography and
purified AHL-lactonase was applied for the control of biofilm formation in P.
aeruginosa PAO1. The results showed that purified AHL-lactonase obtained with a
molecular weight about 30kDa was able to inhibit more than 70% of biofilm in P.
aeruginosa PAO1 (P<0.001). Antibiofilm activity of AHL-lactonase was correlated
well with results from staining technique used to determine inhibition of biomass
and viable cell activity. Therefore, results unambiguously confirm that the AHL
lactonase from E. aerogenes VT66 could be used as antibiofilm therapeutics in P.
aeruginosa associated biomedical applications.
PMID- 26432366
TI - Preparation of lignosulfonate-acrylamide-chitosan ternary graft copolymer and its
flocculation performance.
AB - As flocculant plays an important role in wastewater treatment, searching for high
efficient and cost-effective flocculants has always become the challenge in
chemical industry. In the current work, lignosulfonate-acrylamide-chitosan
ternary copolymer was designed and prepared as a new kind of flocculant. The
elemental analysis and structure characterization of FTIR and XRD showed that
acrylamide successfully grafted onto the two natural polymers and amorphous
macromolecules were formed. The natural polymers-based flocculant was water
soluble and pH independent. As it had multiple functional groups from the raw
materials, the amphoteric flocculant showed high color removal efficiency to
anionic (acid blue 113, >95%), neutral (reactive black 5, >95%) and cationic dyes
(methyl orange, >50%) in a wide range of flocculant dosage and pH windows. The
ternary flocculant, based on lignosulfonate, chitosan, and acrylamide, might be a
promising material in practical applications from the perspective of cost, source
and performance.
PMID- 26432368
TI - Isolation, purification, and antioxidant activities of degraded polysaccharides
from Enteromorpha prolifera.
AB - In the present study, purification and characterization of enzymatic hydrolysates
of polysaccharide from Enteromorpha prolifera (HPE) are described. HPE was
sequentially purified by DEAE Cellulose-52 chromatography and Sephadex G-100
chromatography to afford three fractions, namely, PHPE1, PHPE2, and PHPE3.
Molecular weights of these three fractions were measured to be 103, 45.4, and
9.8kDa, respectively, using high performance gel permeation chromatography
(HPGPC). The three fractions were evaluated for their antioxidant activities by
determining their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH),
hydroxyl, and superoxide anion radicals. PHPE2 was found to possess the strongest
scavenging ability. GC-MS analysis indicates that PHPE2 is mainly composed of
mannose, xylose, and glucose.
PMID- 26432369
TI - Effect of ultrasonication, pH and heating on stability of apricot gum
lactoglobuline two layer nanoemulsions.
AB - The objectives of this study were to evaluate the effect of apricot gum
lactoglobuline (AG/LgC) ratio, thermal treatment, sonication with different times
and amplitudes and pH, on double layer sunflower oil in water emulsion stability.
The emulsion stability was determined by the evaluation of emulsion performance
indices including particle size, zeta potential, creaming and emulsion volume
stability during 10 days of storage. Applying AG and LgC with the ratio of 12.5:1
AG:LgC, in order to obtain double layer oil in water emulsion, could result in a
completely stable nano-emulsions during 10 days storage in room temperature. The
ultrasound treatment significantly increased the emulsion stability. A 10min
ultrasound treatment with the amplitude of 25% was the optimum conditions for
ultra-sonication. The best temperature for thermal treatment and the best pH, in
order to improve the emulsion's stability, was 50 degrees C and 3, respectively.
PMID- 26432370
TI - Synthesis of magnetic graphene nanocomposites decorated with ionic liquids for
fast lead ion removal.
AB - Seeking highly-efficient, low-cost and robust methods to remove metal ions from
aqueous solutions is very much in demand. Here, we developed a novel magnetic
composite bio-adsorbent, graphene oxide and magnetic chitosan-ionic liquids
(GOMCS-ILs), for removing Pb(II) from water. This was the first time to combine
ionic liquids and graphene oxide and magnetic chitosan, and apply to the
adsorption of metal ions. The addition of ionic liquids can not only improve the
dispersivity of the adsorbent, but also increase the adsorption sites. The
characteristic result of FTIR, SEM, and XRD showed that GOMCS-ILs were prepared
with large surface area and good magnetic responsiveness. The influence of
various analytical parameters on the adsorption of Pb(II) such as pH, contact
time, and initial ion concentration were studied in detail. The adsorption
followed a pseudo second order kinetics. The equilibrium adsorption was well
described by the Langmuir isotherm model and the maximum adsorption capacity was
to be 85mgg(-1). Moreover, the GOMCS-ILs could be repeatedly used by simple
treatment without obvious structure and performance degradation. These results
demonstrated the potential applications of GOMCS-ILs microspheres in efficient
removal of Pb(II) from wastewater and deep-purification of polluted water.
PMID- 26432371
TI - Biodegradable polymer based ternary blends for removal of trace metals from
simulated industrial wastewater.
AB - The ternary blends consisting of Chitosan (CS), Nylon 6 (Ny 6) and
Montmorillonite clay (MM clay) were prepared by the solution blending method with
glutaraldehyde. The prepared ternary blends were characterization by Fourier
transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Thermo
gravimetric analysis (TGA), Differential scanning calorimetry (DSC) and Scanning
electron microscope (SEM). The FTIR results showed that the strong intermolecular
hydrogen bondings were established between chitosan, nylon 6 and montmorillonite
clay. TGA showed the thermal stability of the blend is enhanced by glutaraldehyde
as Crosslink agent. Results of XRD indicated that the relative crystalline of the
pure chitosan film was reduced when the polymeric network was reticulated by
glutaraldehyde. Finally, the results of scanning electron microscopy (SEM)
indicated that the morphology of the blend was rough and heterogenous. Further,
it confirms the interaction between the functional groups of the blend
components. The extent of removal of the trace metals was found to be almost the
same. The removal of these metals at different pH was also done and the maximum
removal of the metals was observed at pH 4.5 for both trace metals. Adsorption
studies and kinetic analysis have also been made. Moreover, the protonation of
amine groups is induced an electrostatic repulsion of cations. When the pH of the
solution was more than 5.5, the sorption rate began to decrease. Besides, the
quantity of adsorbate on absorbent was fitted as a function in Langmuir and
Freundlich isotherm. The sorption kinetics was tested for pseudo first order and
pseudo second order reaction. The kinetic experimental data correlated with the
second order kinetic model and rate constants of sorption for kinetic models were
calculated and accordingly, the correlation coefficients were obtained.
PMID- 26432372
TI - Schiff base - Chitosan grafted L-monoguluronic acid as a novel solid-phase
adsorbent for removal of congo red.
AB - A novel modified chitosan adsorbent (GL-SBCS) was synthesized by covalently
grafting a Schiff base-chitosan (SBCS) onto the surface of l-monoguluronic acid.
Physico-chemical investigation on the adsorption of congo red, an anionic azo dye
by GL-SBCS has been carried out. The effect of different weight contents of
chitosan in GL-SBCS composite, adsorbent dosage, initial pH and contract time
were studied in detail using batch adsorption. Results showed that GL-SBCS
exhibited better than normal CS and l-monoguluronic acid. Further investigation
demonstrated that the adsorption pattern fitted well with the Langmuir model
(R(2)>0.99) but less-satisfied the Freundlich model. Both ionic interaction as
well as physical forces is responsible for binding of congo red with GL-SBCS as
determined by zeta potential measurement Both sodium chloride and sodium dodecyl
sulfate significantly influenced the adsorption process. SBCS would be a good
method and resource to increase absorption efficiency for the removal of anionic
dyes in a wastewater treatment process.
PMID- 26432373
TI - Optimization of rhamnolipid production by biodegrading bacterial isolates using
Plackett-Burman design.
AB - Biosurfactants are biological surfactants produced by microorganisms. Pseudomonas
species are well known for the production of the rhamnolipid biosurfactant. In
this work, the production of rhamnolipid biosurfactant by Pseudomonas spp. was
investigated and further optimized. Two Plackett-Burman designs to study the
effect of carbon source, nitrogen source, C/N ratio, iron concentration,
magnesium concentration, phenol toxicity, pH, temperature, agitation and sampling
time were tested. The first design revealed an optimization that increased
biosurfactant productivity by almost two to fivefolds for the tested isolates.
However, using the second design showed no remarkable increase in biosurfactant
productivity. An additional validation run was adopted using the predicted
optimal medium with predicted optimal conditions. The validation run showed
remarkable increase in the productivity of the tested isolates. The use of
microorganisms with biodegradation ability coupled with optimization of the
parameters affecting productivity provides an efficient strategy for
biosurfactant production.
PMID- 26432375
TI - Thoracic outlet syndrome.
PMID- 26432374
TI - Therapeutic efficacy of a polysaccharide isolated from Cordyceps sinensis on
hypertensive rats.
AB - This study was aimed to investigate the antihypertensive effect of a
polysaccharide fraction from Cordyceps sinensis on spontaneously hypertensive
rats (SHR). The CSP1, one component of Cordyceps sinensis polysaccharides (CSP),
was obtained after water extraction, deproteinization, de-colorization and
purification with DEAE-cellulose 52. And a more homogeneous component CSP1-2 was
obtained using Sepharose CL-6B chromatography. CSP1-2 mainly consisted of
mannose, glucose and galactose in a molar ratio of about 2:2:1 and its average
molecular weight was approximately 2.70*10(4)Da. Pharmacological tests showed
that CSP1, in which the CSP1-2 was its main component, had antihypertensive
effect by stimulating the secretion of vasodilator NO, decreasing the level of ET
1, epinephrine, noradrenaline and angiotensin II, inhibiting the increase of
transforming growth factor beta1 (TGF-beta1) and lowering the level of
inflammatory mediator of C-reactive protein (CRP). These results suggested that
CSP1 may possess high potential in treating hypertension.
PMID- 26432377
TI - Observation of interactive behavior increases corticospinal excitability in
humans: A transcranial magnetic stimulation study.
AB - In humans, observation of others' behaviors increases corticospinal excitability
(CSE), which is interpreted in the contexts of motor resonance and the "mirror
neuron system" (MNS). It has been suggested that observation of another
individual's behavior manifests an embodied simulation of his/her mental state
through the MNS. Thus, the MNS may involve understanding others' intentions of
behaviors, thoughts, and emotions (i.e., social cognition), and may therefore
exhibit a greater response when observing human-interactive behaviors that
require a more varied and complex understanding of others. In the present study,
transcranial magnetic stimulation was applied to the primary motor cortex of
participants observing human-interactive behaviors between two individuals (c.f.
one person reaching toward an object in another person's hand) and non
interactive individual behavior (c.f. one person reaching toward an object on a
dish). We carefully controlled the kinematics of behaviors in these two
conditions to exclude potential effects of MNS activity changes associated with
kinematic differences between visual stimuli. Notably, motor evoked potentials,
that reflect CSE, from the first dorsal interosseous muscle exhibited greater
amplitude when the participants observed interactive behaviors than when they
observed non-interactive behavior. These results provide neurophysiological
evidence that the MNS is activated to a greater degree during observation of
human-interactive behaviors that contain additional information about the
individuals' mental states, supporting the view that the MNS plays a critical
role in social cognition in humans.
PMID- 26432378
TI - Transition from reactive control to proactive control across conflict adaptation:
An sLORETA study.
AB - In a flanker task, behavioral performance is modulated by previous trial
compatibility (i.e., conflict adaptation); a longer response time (RT) is found
for a compatible stimulus preceded by an incompatible stimulus than by a
compatible stimulus, whereas a shorter RT is found for an incompatible stimulus
preceded by an incompatible stimulus than by a compatible stimulus. We examined
the temporal characteristics of cognitive control across conflict adaptation
using prestimulus electroencephalogram oscillatory activity and an event-related
potential component, N1. Prestimulus frontal (Fz) and posterior (O1 and O2)
alpha1 (7-9 Hz) and alpha2 (10-13 Hz) activities were enhanced in trials preceded
by incompatible stimuli more than those preceded by compatible stimuli.
Furthermore, there were significant differences of alpha2 current densities
between previous trial compatibilities in the superior/medial frontal cortex. We
suggested that the modulation of alpha activity by previous trial compatibility
was associated with proactive attentional control. N1 amplitude was decreased in
trials preceded by incompatible stimuli more than in those preceded by compatible
stimuli. N1 current densities in the right inferior frontal cortex were smaller
for an incompatible stimulus preceded by an incompatible stimulus than those
preceded by a compatible stimulus, suggesting that demands of transient cognitive
control induced by an incompatible stimulus were decreased by the proactive
control. Moreover, correlational analysis showed that participants with a larger
increase in alpha2 activity tended to have a larger decrease in N1 in trials
preceded by incompatible stimulus. These findings revealed that the manner of
cognitive control for the incompatible stimulus was transited from reactive
control to proactive control across conflict adaptation.
PMID- 26432379
TI - Reduced sensitivity to neutral feedback versus negative feedback in subjects with
mild depression: Evidence from event-related potentials study.
AB - Many previous event-related potential (ERP) studies have linked the feedback
related negativity (FRN) component with medial frontal cortex processing and
associated this component with depression. Few if any studies have investigated
the processing of neutral feedback in mildly depressive subjects in the normal
population. Two experiments compared brain responses to neutral feedback with
behavioral performance in mildly depressed subjects who scored highly on the Beck
Depression Inventory (high BDI) and a control group with lower BDI scores (low
BDI). In the first study, the FRN component was recorded when neutral, negative
or positive feedback was pseudo-randomly delivered to the two groups in a time
estimation task. In the second study, real feedback was provided to the two
groups in the same task in order to measure their actual accuracy of performance.
The results of experiment one (Exp. 1) revealed that a larger FRN effect was
elicited by neutral feedback than by negative feedback in the low BDI group, but
no significant difference was found between neutral condition and negative
condition in the High BDI group. The present findings demonstrated that
depressive tendencies influence the processing of neutral feedback in medial
frontal cortex. The FRN effect may work as a helpful index for investigating
cognitive bias in depression in future studies.
PMID- 26432380
TI - Chemical and biological assessment of Jujube (Ziziphus jujuba)-containing herbal
decoctions: Induction of erythropoietin expression in cultures.
AB - Jujubae Fructus, known as jujube or Chinese date, is the fruit of Ziziphus jujuba
(Mill.), which not only serves as daily food, but acts as tonic medicine and
health supplement for blood nourishment and sedation. According to Chinese
medicine, jujube is commonly included in herbal mixtures, as to prolong, enhance
and harmonize the efficiency of herbal decoction, as well as to minimize the
toxicity. Here, we aim to compare the chemical and pharmacological properties of
three commonly used jujube-containing decoctions, including Guizhi Tang (GZT),
Neibu Dangguijianzhong Tang (NDT) and Zao Tang (ZOT). These decoctions share
common herbs, i.e. Glycyrrhizae Radix et Rhizoma Praeparata cum Melle, Zingiberis
Rhizoma Recens and Jujube, and they have the same proposed hematopoietic
functions. The amount of twelve marker biomolecules deriving from different herbs
in the decoctions were determined by LC-MS, and which served as parameters for
chemical standardization. In general, three decoctions showed common chemical
profiles but with variations in solubilities of known active ingredients. The
chemical standardized decoctions were tested in cultured Hep3B cells. The herbal
treatment stimulated the amount of mRNA and protein expressions of erythropoietin
(EPO) via the activation of hypoxia response elements: the three herbal
decoctions showed different activation. The results therefore demonstrated the
hematopoietic function of decoctions and explained the enhancement of jujube
function within a herbal mixture.
PMID- 26432381
TI - A novel mouse model provides insights into the neutropenia associated with the
ribosomopathy Shwachman-Diamond syndrome.
PMID- 26432384
TI - Comment on "acute lymphoblastic leukemia and adiponcosis" by M. Bifilco and AM
Malfitano.
PMID- 26432382
TI - JAK kinase targeting in hematologic malignancies: a sinuous pathway from
identification of genetic alterations towards clinical indications.
AB - Constitutive JAK-STAT pathway activation occurs in most myeloproliferative
neoplasms as well as in a significant proportion of other hematologic
malignancies, and is frequently a marker of poor prognosis. The underlying
molecular alterations are heterogeneous as they include activating mutations in
distinct components (cytokine receptor, JAK, STAT), overexpression (cytokine
receptor, JAK) or rare JAK2 fusion proteins. In some cases, concomitant loss of
negative regulators contributes to pathogenesis by further boosting the
activation of the cascade. Exploiting the signaling bottleneck provided by the
limited number of JAK kinases is an attractive therapeutic strategy for
hematologic neoplasms driven by constitutive JAK-STAT pathway activation.
However, given the conserved nature of the kinase domain among family members and
the interrelated roles of JAK kinases in many physiological processes, including
hematopoiesis and immunity, broad usage of JAK inhibitors in hematology is
challenged by their narrow therapeutic window. Novel therapies are, therefore,
needed. The development of more selective inhibitors is a questionable strategy
as such inhibitors might abrogate the beneficial contribution of alleviating the
cancer-related pro-inflammatory microenvironment and raise selective pressure to
a threshold that allows the emergence of malignant subclones harboring drug
resistant mutations. In contrast, synergistic combinations of JAK inhibitors with
drugs targeting cascades that work in concert with JAK-STAT pathway appear to be
promising therapeutic alternatives to JAK inhibitors as monotherapies.
PMID- 26432383
TI - European Myeloma Network guidelines for the management of multiple myeloma
related complications.
AB - The European Myeloma Network provides recommendations for the management of the
most common complications of multiple myeloma. Whole body low-dose computed
tomography is more sensitive than conventional radiography in depicting
osteolytic disease and thus we recommend it as the novel standard for the
detection of lytic lesions in myeloma (grade 1A). Myeloma patients with adequate
renal function and bone disease at diagnosis should be treated with zoledronic
acid or pamidronate (grade 1A). Symptomatic patients without lytic lesions on
conventional radiography can be treated with zoledronic acid (grade 1B), but its
advantage is not clear for patients with no bone involvement on computed
tomography or magnetic resonance imaging. In asymptomatic myeloma,
bisphosphonates are not recommended (grade 1A). Zoledronic acid should be given
continuously, but it is not clear if patients who achieve at least a very good
partial response benefit from its continuous use (grade 1B). Treatment with
erythropoietic-stimulating agents may be initiated in patients with persistent
symptomatic anemia (hemoglobin <10g/dL) in whom other causes of anemia have been
excluded (grade 1B). Erythropoietic agents should be stopped after 6-8 weeks if
no adequate hemoglobin response is achieved. For renal impairment, bortezomib
based regimens are the current standard of care (grade 1A). For the management of
treatment-induced peripheral neuropathy, drug modification is needed (grade 1C).
Vaccination against influenza is recommended; vaccination against streptococcus
pneumonia and hemophilus influenza is appropriate, but efficacy is not guaranteed
due to suboptimal immune response (grade 1C). Prophylactic aciclovir (or
valacyclovir) is recommended for patients receiving proteasome inhibitors,
autologous or allogeneic transplantation (grade 1A).
PMID- 26432385
TI - Comparison of five Lonicera flowers by simultaneous determination of multi
components with single reference standard method and principal component
analysis.
AB - The flowers of Lonicera japonica Thunb. were extensively used to treat many
diseases. As the demands for L. japonica increased, some related Lonicera plants
were often confused or misused. Caffeoylquinic acids were always regarded as
chemical markers in the quality control of L. japonica, but they could be found
in all Lonicera species. Thus, a simple and reliable method for the evaluation of
different Lonicera flowers is necessary to be established. In this work a method
based on single standard to determine multi-components (SSDMC) combined with
principal component analysis (PCA) for control and distinguish of Lonicera
species flowers have been developed. Six components including three
caffeoylquinic acids and three iridoid glycosides were assayed simultaneously
using chlorogenic acid as the reference standard. The credibility and feasibility
of the SSDMC method were carefully validated and the results demonstrated that
there were no remarkable differences compared with external standard method.
Finally, a total of fifty-one batches covering five Lonicera species were
analyzed and PCA was successfully applied to distinguish the Lonicera species.
This strategy simplifies the processes in the quality control of multiple
componential herbal medicine which effectively adapted for improving the quality
control of those herbs belonging to closely related species.
PMID- 26432386
TI - Dereplication of antioxidant compounds in Bene (Pistacia atlantica subsp. mutica)
hull using a multiplex approach of HPLC-DAD, LC-MS and (1)H NMR techniques.
AB - Bene is an edible fruit from the tree Pistacia atlantica subsp. mutica, and is of
steadily growing interest in recent years due to its significant antioxidant
properties and potential health benefits. An antioxidant activity-guided
fractionation of the methanol extract from Bene hull together with an integrated
approach of HPLC-DAD, LC-MS and (1)H NMR techniques led to the identification of
main antioxidant phenolic compounds for the first time. Radical scavenging
activity of each fraction/compound was tested using DPPH and FRAP assays. The
phenolic content of the fractions was also determined by Folin-Ciocalteu's
method. The main identified antioxidant compounds were luteolin (46.53% w/w of
total extract), gallic acid (9.84% w/w), 2"-O-galloylisoquercitrin (0.53% w/w),
quercetin 3-rutinoside (0.34% w/w) and 2"-O-cis-caffeoylquercitrin (0.26% w/w).
The minor antioxidant compounds were also identified by liquid chromatography
positive/negative electrospray ionization tandem mass spectrometry. The structure
antioxidant activity relationship of identified phenolics are also discussed in
this paper.
PMID- 26432388
TI - Identification of proteins from human permanent erupted enamel.
AB - Proteins from the extracellular matrix of enamel are highly specific and
necessary for proper enamel formation. Most proteins are removed from the matrix
by enamel proteases before complete mineralization is achieved; however, some
residual protein fragments persist in the mineralized matrix of erupted enamel.
So far, only amelogenin peptides obtained by traditional bottom-up proteomics
have been recovered and identified in human permanent erupted enamel. In this
study, we hypothesize that other enamel-specific proteins are also found in human
permanent enamel, by analysing human erupted third molars. Pulverized enamel was
used to extract proteins, and the protein extract was subjected directly to
liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS) without a
previous trypsin-digestion step. Amelogenin and non-amelogenin proteins
(ameloblastin and enamelin) were succesfully identified. The sequences of the
naturally occurring peptides of these proteins are reported, finding in
particular that most of the peptides from the amelogenin X-isoform come from the
tyrosine-rich amelogenin peptide (TRAP) and that some were identified in all
specimens. In conclusion, our LC-MS/MS method without trypsin digestion increased
the coverage of identification of the enamel proteome from a few amelogenin
peptides to a higher number of peptides from three enamel-specific proteins.
PMID- 26432389
TI - Greater rhea (Rhea americana) external morphology at different stages of
embryonic and fetal development.
AB - Knowledge of wild species embryonic development is important for their
maintenance in captivity or the wild. The objective of the present study was to
characterize the external morphology and define the biometry of greater rhea
embryos and fetuses at different stages of development. A total of 41 embryos and
fetuses were analyzed to describe their external morphology using a stereoscopic
microscope. The crown-rump (CR), total length (TL), cephalocaudal length (CCL),
biparietal diameter (BPD), beak, humerus and tibio-tarsal lengths were measured
by digital pachymeter, millimetric scale ruler and cotton thread. The weight of
the embryos and fetuses was measured on digital scales. The greater rhea embryos
at 5, 6 and 7 days incubation presented a "C" shape. At 9, 10 and 11 days the
eyes were big and pigmented. At 11, 12 and 13 days the eyelid covered more than
half the eye, resulting in an oval slit. In 14 and 15 day-old embryos, the skin
was still thin and the ribs evident, but at 18 days this structure was thicker.
In embryos at 21 and 27 days of development closed eyelids were observed forming
an eyelid slit, and the eye ball was less pronounced at 27 days. Weight gain
presented an exponential growth curve, while measurements such as TL, DBP, beak,
humerus and tibio-tarsal length had linear growth over time. Thus it was possible
to characterize the greater rhea embryos and fetuses at several incubation ages
using their external morphology and morphometric analyses.
PMID- 26432387
TI - Genetics and physiology of cell wall polysaccharides in the model C4 grass,
Setaria viridis spp.
AB - BACKGROUND: Setaria viridis has emerged as a model species for the larger C4
grasses. Here the cellulose synthase (CesA) superfamily has been defined, with an
emphasis on the amounts and distribution of (1,3;1,4)-beta-glucan, a cell wall
polysaccharide that is characteristic of the grasses and is of considerable value
for human health. METHODS: Orthologous relationship of the CesA and Poales
specific cellulose synthase-like (Csl) genes among Setaria italica (Si), Sorghum
bicolor (Sb), Oryza sativa (Os), Brachypodium distachyon (Bradi) and Hordeum
vulgare (Hv) were compared using bioinformatics analysis. Transcription profiling
of Csl gene families, which are involved in (1,3;1,4)-beta-glucan synthesis, was
performed using real-time quantitative PCR (Q-PCR). The amount of (1,3;1,4)-beta
glucan was measured using a modified Megazyme assay. The fine structures of the
(1,3;1,4)-beta-glucan, as denoted by the ratio of cellotriosyl to cellotetraosyl
residues (DP3:DP4 ratio) was assessed by chromatography (HPLC and HPAEC-PAD). The
distribution and deposition of the MLG was examined using the specific antibody
BG-1 and captured using fluorescence and transmission electron microscopy (TEM).
RESULTS: The cellulose synthase gene superfamily contains 13 CesA and 35 Csl
genes in Setaria. Transcript profiling of CslF, CslH and CslJ gene families
across a vegetative tissue series indicated that SvCslF6 transcripts were the
most abundant relative to all other Csl transcripts. The amounts of (1,3;1,4)
beta-glucan in Setaria vegetative tissues ranged from 0.2% to 2.9% w/w with much
smaller amounts in developing grain (0.003% to 0.013% w/w). In general, the
amount of (1,3;1,4)-beta-glucan was greater in younger than in older tissues. The
DP3:DP4 ratios varied between tissue types and across developmental stages, and
ranged from 2.4 to 3.0:1. The DP3:DP4 ratios in developing grain ranged from 2.5
to 2.8:1. Micrographs revealing the distribution of (1,3;1,4)-beta-glucan in
walls of different cell types and the data were consistent with the quantitative
(1,3;1,4)-beta-glucan assays. CONCLUSION: The characteristics of the cellulose
synthase gene superfamily and the accumulation and distribution of (1,3;1,4)-beta
glucans in Setaria are similar to those in other C4 grasses, including sorghum.
This suggests that Setaria is a suitable model plant for cell wall polysaccharide
biology in C4 grasses.
PMID- 26432390
TI - Sugar-Sweetened Beverages: Children's Perceptions, Factors of Influence, and
Suggestions for Reducing Intake.
AB - OBJECTIVES: This study aimed to gain an in-depth understanding of children's
perceptions of sugar-sweetened beverages (SSBs). DESIGN: Nine focus groups were
conducted in grade 5 and 6 elementary schoolchildren. SETTING: Nine urban and
rural elementary schools in London, Ontario, Canada. PARTICIPANTS: Fifty-one
children, 58% of which were male, 52% of whom were in grade 5, and 84% of whom
were Caucasian. PHENOMENON OF INTEREST: Children's views on sugar-sweetened
beverages. ANALYSIS: Three researchers conducted inductive content analysis on
the data independently using the principles of the immersion-crystallization
method. RESULTS: Participants had a high level of awareness of beverages and
their health effects, which was primarily targeted at the sugar content. Dominant
factors that influenced children's beverage choices and consumption patterns
included taste, parental control practices, accessibility, and advertising.
Participants identified a wide array of strategies to reduce SSB consumption in
children, including educational strategies for both children and parents and
policy-level changes at both the government and school levels. CONCLUSIONS AND
IMPLICATIONS: Despite a high level of awareness of SSBs, children believed that
further education and policies regarding SSBs were warranted. These data may
prove helpful in designing effective interventions targeted at children and
parents to reduce SSB consumption by children.
PMID- 26432391
TI - TCEANC2 rs10788972 and rs12046178 variants in the PARK10 region in Chinese Han
patients with sporadic Parkinson's disease.
AB - Parkinson's disease (PD) is the second most common chronic neuronal degeneration
disorder with motor and nonmotor clinical features. The rs10788972 variant of the
transcription elongation factor A (SII) N-terminal and central domain containing
2 (TCEANC2) gene in the PARK10 region was recently identified to be strongly
related to sporadic PD in the American population. To evaluate whether the same
variant is associated with sporadic PD in Chinese Han population, we researched
513 sporadic PD patients and 512 normal controls of Chinese Han ethnicity in
Mainland China. No significant difference in genotypic and allelic distributions
between patients and control groups for either rs10788972 (for genotypic
distribution, chi(2) = 0.412, p = 0.814, and for allelic distribution, chi(2) =
0.280, p = 0.597) or its neighbor marker rs12046178 (for genotypic distribution,
chi(2) = 1.500, p = 0.472, and for allelic distribution, chi(2) = 1.339, p =
0.247) was found. Our data suggest that neither variant is related to sporadic PD
in Chinese Han population.
PMID- 26432392
TI - Origin of the hungry caterpillar: Evolution of fasting in slug moths (Insecta:
Lepidoptera: Limacodidae).
AB - Studies of caterpillar defense strategy evolution typically focus on aposematic
coloration, gregarious behavior, and/or chemical defense. In the slug moth family
Limacodidae, the evolution of chemical defense is coupled to the life history
trait of first instar feeding behaviors. In nettle caterpillars, the first
instars fast and molt into a second instar that feeds. In contrast, gelatines and
monkey slug larval forms feed in the first instar. This study focused on whether
the evolution of fasting associated with the nettle morphology was a derived
trait of single or multiple origins. Twenty-nine species of Limacodidae
(including one Chrysopolominae) representing 27 genera and four outgroup species
with known first and final instar morphologies and behaviors were included. Four
out-group species representing Megalopygidae (1 sp), Dalceridae (1 sp) and
Aididae (2 sp) were included. These were sequenced for three molecular markers
for a total of 4073 bp, mitochondrial COI (~1500 bp), 18S (~1900 bp) and the D2
region of 28S (approximately 670 bp). Maximum likelihood and Bayesian analyses
were conducted. The resulting phylogeny and comparative analysis of feeding
strategy revealed that the nettle caterpillar morphology and behavior of larval
fasting may have a single origin.
PMID- 26432393
TI - Biogeography of the Malagasy Celastraceae: Multiple independent origins followed
by widespread dispersal of genera from Madagascar.
AB - Of the 97 currently recognized genera of Celastraceae, 19 are native to
Madagascar, including six endemics. In this study we conducted the most thorough
phylogenetic analysis of Celastraceae yet completed with respect to both
character and taxon sampling, and include representatives of five new endemic
genera. Fifty-one new accessions, together with 328 previously used accessions of
Celastrales, were sampled for morphological characters, two rDNA gene regions,
and two plastid gene regions. The endemic Malagasy genera are resolved in two
separate lineages-Xenodrys by itself and all other endemic genera in a clade that
also includes four lineages inferred to have dispersed from Madagascar: Brexia
madagascariensis (Mascarene Islands, coastal Africa), Elaeodendron (West Indies,
Africa to New Caledonia), and Pleurostylia (Africa to New Caledonia). Of the 12
extant Malagasy Celastraceae lineages identified, eight are clearly of African
origin. The origins of the remaining four lineages are less clear, but reasonable
possibilities include America, Eurasia, Africa, southern India, Malesia, and
Australia. Based on 95% credible age intervals from fossil-calibrated molecular
dating, all 12 extant Malagasy Celastraceae lineages appear to have arisen
following dispersal after the separation of Madagascar from other landmasses
within the last 70 million years.
PMID- 26432394
TI - Molecular data reveal spatial and temporal patterns of diversification and a
cryptic new species of lowland Stenocercus Dumeril & Bibron, 1837 (Squamata:
Tropiduridae).
AB - Phylogenetic studies have uncovered biogeographic patterns and the associated
diversification processes of Neotropical wet forest taxa, yet the extensive open
and drier biomes have received much less attention. In the Stenocercus lizard
radiation, restricted sampling and phylogenetic information have limited
inferences about the timing, spatial context, and environmental drivers of
diversification in the open and dry lowland settings of eastern and southern
South America. Based on new DNA sequence data of previously unsampled species, we
provide an updated historical biogeographic hypothesis of Stenocercus. We infer
phylogenetic relationships, estimate divergence times, and track ancestral
distributions, asking whether cladogenetic events within the genus correlate to
reported shifts in South American landscapes during the past 30millionyears,
focusing in the open and drier areas. To examine correlations between genetic and
ecological divergence, we extracted environmental data from occurrence records
and estimated climatic envelopes occupied by lowland taxa. Our results suggest
that Stenocercus began to diversify around the South American Midwest by the late
Oligocene. We recovered two main lowland and two main Andean clades within the
genus; within both Andean clades, most cladogenetic events date back to the
Miocene, synchronously with the most intense phase of Andean uplift. In the
western clade of lowland Stenocercus, species ranges and divergence times are
consistent with major landscape shifts at the upper Guapore and Paraguay River
basins as a result of Andean orogeny, suggesting vicariant speciation. By
contrast, in the 'horned' lowland clade, we find evidence that dispersal and
ecological differentiation have shaped species divergences and current ranges in
the Brazilian Cerrado, Caatinga, Pampas and Atlantic Forest, possibly under a
vanishing refuge scenario. Lastly, our phylogenetic results indicate two
divergent clades within the formerly recognized taxon S. sinesaccus, and further
evaluation of morphological data corroborates the existence of a distinct, new
species of Stenocercus, here described. The new taxon occurs in the Chapada dos
Parecis massif in the Brazilian states of Mato Grosso and Rondonia.
PMID- 26432396
TI - Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.
AB - Canine degenerative myelopathy (CDM) represents a unique naturally occurring
animal model for human amyotrophic lateral sclerosis (ALS) because of similar
clinical signs, neuropathologic findings, and involvement of the superoxide
dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem
through microscopic detection of axonal degeneration, demyelination and
astroglial proliferation, which is more severe in the dorsal columns of the
thoracic spinal cord and in the dorsal portion of the lateral funiculus.
Interestingly, the muscle acetylcholine receptor complexes are intact in CDM
prior to functional impairment, thus suggesting that muscle atrophy in CDM does
not result from physical denervation. Moreover, since sensory involvement seems
to play an important role in CDM progression, a more careful investigation of the
sensory pathology in ALS is also warranted. The importance of SOD1 expression
remains unclear, while oxidative stress and denatured ubiquinated proteins appear
to play a crucial role in the pathogenesis of CDM. In this updated narrative
review we performed a systematic search of the published studies on CDM that may
shed light on the pathophysiological mechanisms of human ALS. A better
understanding of the factors that determine the disease progression in CDM may be
beneficial for the development of effective treatments for ALS.
PMID- 26432395
TI - Genetic and structural analyses of cytochrome P450 hydroxylases in sex hormone
biosynthesis: Sequential origin and subsequent coevolution.
AB - Biosynthesis of steroid hormones in vertebrates involves three cytochrome P450
hydroxylases, CYP11A1, CYP17A1 and CYP19A1, which catalyze sequential steps in
steroidogenesis. These enzymes are conserved in the vertebrates, but their origin
and existence in other chordate subphyla (Tunicata and Cephalochordata) have not
been clearly established. In this study, selected protein sequences of CYP11A1,
CYP17A1 and CYP19A1 were compiled and analyzed using multiple sequence alignment
and phylogenetic analysis. Our analyses show that cephalochordates have sequences
orthologous to vertebrate CYP11A1, CYP17A1 or CYP19A1, and that echinoderms and
hemichordates possess CYP11-like but not CYP19 genes. While the cephalochordate
sequences have low identity with the vertebrate sequences, reflecting
evolutionary distance, the data show apparent origin of CYP11 prior to the
evolution of CYP19 and possibly CYP17, thus indicating a sequential origin of
these functionally related steroidogenic CYPs. Co-occurrence of the three CYPs in
early chordates suggests that the three genes may have coevolved thereafter, and
that functional conservation should be reflected in functionally important
residues in the proteins. CYP19A1 has the largest number of conserved residues
while CYP11A1 sequences are less conserved. Structural analyses of human CYP11A1,
CYP17A1 and CYP19A1 show that critical substrate binding site residues are highly
conserved in each enzyme family. The results emphasize that the steroidogenic
pathways producing glucocorticoids and reproductive steroids are several hundred
million years old and that the catalytic structural elements of the enzymes have
been conserved over the same period of time. Analysis of these elements may help
to identify when precursor functions linked to these enzymes first arose.
PMID- 26432397
TI - Effortless assignment with 4D covariance sequential correlation maps.
AB - Traditional Nuclear Magnetic Resonance (NMR) assignment procedures for proteins
rely on preliminary peak-picking to identify and label NMR signals. However, such
an approach has severe limitations when signals are erroneously labeled or
completely neglected. The consequences are especially grave for proteins with
substantial peak overlap, and mistakes can often thwart entire projects. To
overcome these limitations, we previously introduced an assignment technique that
bypasses traditional pick peaking altogether. Covariance Sequential Correlation
Maps (COSCOMs) transform the indirect connectivity information provided by
multiple 3D backbone spectra into direct (H, N) to (H, N) correlations. Here, we
present an updated method that utilizes a single four-dimensional spectrum rather
than a suite of three-dimensional spectra. We demonstrate the advantages of 4D
COSCOMs relative to their 3D counterparts. We introduce improvements accelerating
their calculation. We discuss practical considerations affecting their quality.
And finally we showcase their utility in the context of a 52 kDa cyclization
domain from a non-ribosomal peptide synthetase.
PMID- 26432398
TI - The use of a selective saturation pulse to suppress t1 noise in two-dimensional
(1)H fast magic angle spinning solid-state NMR spectroscopy.
AB - A selective saturation pulse at fast magic angle spinning (MAS) frequencies
(60+kHz) suppresses t1 noise in the indirect dimension of two-dimensional (1)H
MAS NMR spectra. The method is applied to a synthetic nucleoside with an intense
methyl (1)H signal due to triisopropylsilyl (TIPS) protecting groups. Enhanced
performance in terms of suppressing the methyl signal while minimising the loss
of signal intensity of nearby resonances of interest relies on reducing spin
diffusion--this is quantified by comparing two-dimensional (1)H NOESY-like spin
diffusion spectra recorded at 30-70 kHz MAS. For a saturation pulse centred at
the methyl resonance, the effect of changing the nutation frequency at different
MAS frequencies as well as the effect of changing the pulse duration is
investigated. By applying a pulse of duration 30 ms and nutation frequency 725 Hz
at 70 kHz MAS, a good compromise of significant suppression of the methyl
resonance combined with the signal intensity of resonances greater than 5 ppm
away from the methyl resonance being largely unaffected is achieved. The
effectiveness of using a selective saturation pulse is demonstrated for both
homonuclear (1)H-(1)H double quantum (DQ)/single quantum (SQ) MAS and (14)N-(1)H
heteronuclear multiple quantum coherence (HMQC) two-dimensional solid-state NMR
experiments.
PMID- 26432399
TI - Localized 2D COSY sequences: Method and experimental evaluation for a whole
metabolite quantification approach.
AB - Two-dimensional spectroscopy offers the possibility to unambiguously distinguish
metabolites by spreading out the multiplet structure of J-coupled spin systems
into a second dimension. Quantification methods that perform parametric fitting
of the 2D MRS signal have recently been proposed for resolved PRESS (JPRESS) but
not explicitly for Localized Correlation Spectroscopy (LCOSY). Here, through a
whole metabolite quantification approach, correlation spectroscopy quantification
performances are studied. The ability to quantify metabolite relaxation constant
times is studied for three localized 2D MRS sequences (LCOSY, LCTCOSY and the
JPRESS) in vitro on preclinical MR systems. The issues encountered during
implementation and quantification strategies are discussed with the help of the
Fisher matrix formalism. The described parameterized models enable the
computation of the lower bound for error variance--generally known as the Cramer
Rao bounds (CRBs), a standard of precision--on the parameters estimated from
these 2D MRS signal fittings. LCOSY has a theoretical net signal loss of two per
unit of acquisition time compared to JPRESS. A rapid analysis could point that
the relative CRBs of LCOSY compared to JPRESS (expressed as a percentage of the
concentration values) should be doubled but we show that this is not necessarily
true. Finally, the LCOSY quantification procedure has been applied on data
acquired in vivo on a mouse brain.
PMID- 26432400
TI - Optimizing low impact development (LID) for stormwater runoff treatment in urban
area, Korea: Experimental and modeling approach.
AB - Currently, continued urbanization and development result in an increase of
impervious areas and surface runoff including pollutants. Also one of the
greatest issues in pollutant emissions is the first flush effect (FFE), which
implies a greater discharge rate of pollutant mass in the early part in the
storm. Low impact development (LID) practices have been mentioned as a promising
strategy to control urban stormwater runoff and pollution in the urban ecosystem.
However, this requires many experimental and modeling efforts to test LID
characteristics and propose an adequate guideline for optimizing LID management.
In this study, we propose a novel methodology to optimize the sizes of different
types of LID by conducting intensive stormwater monitoring and numerical modeling
in a commercial site in Korea. The methodology proposed optimizes LID size in an
attempt to moderate FFE on a receiving waterbody. Thereby, the main objective of
the optimization is to minimize mass first flush (MFF), which is an indicator for
quantifying FFE. The optimal sizes of 6 different LIDs ranged from 1.2 mm to 3.0
mm in terms of runoff depths, which significantly moderate the FFE. We hope that
the new proposed methodology can be instructive for establishing LID strategies
to mitigate FFE.
PMID- 26432401
TI - Combined application of ultrasound and SPECT/CT has incremental value in
detecting parathyroid tissue in SHPT patients.
AB - PURPOSE: The goal of this study is to investigate whether combined application of
ultrasound and 99mTc-sestamibi SPECT/CT had the incremental value in accurately
detecting parathyroid tissue in patients with SHPT over either method alone.
PATIENTS AND METHODS: Sixty patients with SHPT on hemodialysis were evaluated
preoperatively with parathyroid 99mTc-sestamibi SPECT/CT scintigraphy and
ultrasound prior to parathyroidectomy. The sensitivity, specificity and accuracy
of 99mTc-sestamibi SPECT/CT scintigraphy, ultrasound and combined application
were determined respectively. RESULTS: The sensitivity, specificity and accuracy
of ultrasound were 81% (155/192), 47% (17/36) and 82% (172/228), respectively.
The sensitivity, specificity and accuracy of 99mTc-sestamibi SPECT/CT were 85%
(163/192), 58% (21/36) and 89% (184/228) respectively. The accuracy of 99mTc
sestamibi SPECT/CT in the diagnosis of parathyroid tissue in patients with SHPT
is significantly higher than that of ultrasound. The sensitivity, specificity and
accuracy of combined application of ultrasound and 99mTc-sestamibi SPECT/CT were
93% (178/192), 61% (22/36) and 97% (200/228). The sensitivity, specificity and
accuracy of combined application of ultrasound and 99mTc-sestamibi SPECT/CT were
higher than those of either ultrasound or 99mTc-sestamibi SPECT/CT. CONCLUSIONS:
The combined application of ultrasound and 99mTc-sestamibi SPECT/CT had
incremental value in accurately detecting parathyroid tissue in patients with
SHPT over either method alone.
PMID- 26432402
TI - Retraction: Meeting Report: Inaugural Chemotherapy-Induced Peripheral Neuropathy
Symposium, Santa Barbara, CA, February 2015.
PMID- 26432403
TI - Suppression of intratumoral CCL22 by type i interferon inhibits migration of
regulatory T cells and blocks cancer progression.
AB - The chemokine CCL22 is abundantly expressed in many types of cancer and is
instrumental for intratumoral recruitment of regulatory T cells (Treg), an
important subset of immunosuppressive and tumor-promoting lymphocytes. In this
study, we offer evidence for a generalized strategy to blunt Treg activity that
can limit immune escape and promote tumor rejection. Activation of innate
immunity with Toll-like receptor (TLR) or RIG-I-like receptor (RLR) ligands
prevented accumulation of Treg in tumors by blocking their immigration.
Mechanistic investigations indicated that Treg blockade was a consequence of
reduced intratumoral CCL22 levels caused by type I IFN. Notably, stable
expression of CCL22 abrogated the antitumor effects of treatment with RLR or TLR
ligands. Taken together, our findings argue that type I IFN blocks the Treg
attracting chemokine CCL22 and thus helps limit the recruitment of Treg to
tumors, a finding with implications for cancer immunotherapy.
PMID- 26432404
TI - Androgen Receptor Upregulation Mediates Radioresistance after Ionizing Radiation.
AB - Clinical trials have established the benefit of androgen deprivation therapy
(ADT) combined with radiotherapy in prostate cancer. ADT sensitizes prostate
cancer to radiotherapy-induced death at least in part through inhibition of DNA
repair machinery, but for unknown reasons, adjuvant ADT provides further survival
benefits. Here, we show that androgen receptor (AR) expression and activity are
durably upregulated following radiotherapy in multiple human prostate cancer
models in vitro and in vivo. Moreover, the degree of AR upregulation correlates
with survival in vitro and time to tumor progression in animal models. We also
provide evidence of AR pathway upregulation, measured by a rise in serum levels
of AR-regulated hK2 protein, in nearly 20% of patients after radiotherapy.
Furthermore, these men were three-fold more likely to experience subsequent
biochemical failure. Collectively, these data demonstrate that radiotherapy can
upregulate AR signaling after therapy to an extent that negatively affects
disease progression and/or survival.
PMID- 26432405
TI - PI3K-mTORC2 but not PI3K-mTORC1 regulates transcription of HIF2A/EPAS1 and
vascularization in neuroblastoma.
AB - Hypoxia-inducible factor (HIF) is a master regulator of cellular responses to
oxygen deprival with a critical role in mediating the angiogenic switch in solid
tumors. Differential expression of the HIF subunits HIF1alpha and HIF2alpha
occurs in many human tumor types, suggesting selective implications to biologic
context. For example, high expression of HIF2alpha that occurs in neuroblastoma
is associated with stem cell-like features, disseminated disease, and poor
clinical outcomes, suggesting pivotal significance for HIF2 control in
neuroblastoma biology. In this study, we provide novel insights into how
HIF2alpha expression is transcriptionally controlled by hypoxia and how this
control is abrogated by inhibition of insulin-like growth factor-1R/INSR-driven
phosphoinositide 3-kinase (PI3K) signaling. Reducing PI3K activity was sufficient
to decrease HIF2alpha mRNA and protein expression in a manner with smaller and
less vascularized tumors in vivo. PI3K-regulated HIF2A mRNA expression was
independent of Akt or mTORC1 signaling but relied upon mTORC2 signaling. HIF2A
mRNA was induced by hypoxia in neuroblastoma cells isolated from metastatic
patient-derived tumor xenografts, where HIF2A levels could be reduced by
treatment with PI3K and mTORC2 inhibitors. Our results suggest that targeting
PI3K and mTORC2 in aggressive neuroblastomas with an immature phenotype may
improve therapeutic efficacy.
PMID- 26432406
TI - The impact of GABA in harpin-elicited biotic stress responses in Nicotiana
tabaccum.
AB - Harpin is a bacterial elicitor protein that was first isolated from Erwinia
amylovora. Infiltration of this elicitor into the leaves of plants activates
systemic acquired resistance against a variety of plant pathogens via the
salicyclic acid defense pathway. The non-protein amino acid, neurotransmission
inhibitor molecule of mammals-GABA- is found in all organisms and is known to be
an important component of stress responses in plants. We hypothesized a possible
interaction between harpin-induced defense responses and GABA shunt. Therefore,
we conducted experiments on harpin-infiltrated tobacco and analyzed the
components of GABA shunt in relation to growth, photosynthesis and H2O2 levels.
RGR, RWC and photosynthetic efficiency were all affected in harpin-infiltrated
tobacco leaves, but the rate of decline was more remarkable on RGR. H2O2 levels
showed significant difference on 7 days after harpin infiltration when the
necrotic lesions were also visible. GABA accumulation was increased and glutamate
levels were decreased parallel to the differences in GDH and GAD enzyme
activities, especially on days 5 and 7 of harpin infiltration. Transcript
abundance of GDH and GAD encoding genes were differentially regulated in harpin
infiltrated leaves as compared to that of control and mock groups. In the present
study, for the first time we showed a relationship between harpin-elicited
responses and GABA in tobacco that was not mediated by H2O2 accumulation. Harpin
infiltration significantly induced the first components of the GABA shunt such as
GDH, GAD, glutamate and GABA in tobacco.
PMID- 26432407
TI - Effect of blue LED light intensity on carotenoid accumulation in citrus juice
sacs.
AB - In the present study, the effects of blue LED light intensity on carotenoid
accumulation and expression of genes related to carotenoid biosynthesis were
investigated in the juice sacs of Satsuma mandarin (Citrus unshiu Marc.) and
Valencia orange (Citrus sinensis Osbeck) in vitro. The results showed that 100
MUmol m(-2)s(-1) blue LED light (100B) was effective for increasing carotenoid
content, especially beta-cryptoxanthin, in Satsuma mandarin after cultured in
vitro for four weeks. In Valencia orange, in contrast, 50 MUmol m(-2)s(-1) blue
LED light (50B) treatment was effective for inducing carotenoid accumulation
through increasing the contents of two major carotenoids, all-trans-violaxanthin
and 9-cis-violaxanthin. In addition, gene expression results showed that the
simultaneous increases in the expression of genes (CitPSY, CitPDS, CitZDS,
CitLCYb2, and CitHYb) involved in producing beta,beta-xanthophylls were well
consistent with the accumulation of beta-cryptoxanthin in Satsuma mandarin under
100B, and violaxanthin in Valencia orange under 50B. The results presented herein
contribute to further elucidating the regulatory mechanism of carotenoid
accumulation by blue LED light.
PMID- 26432408
TI - A large and unusual lung abscess with positive culture to Slackia exigua.
PMID- 26432409
TI - Assessing cyber-user awareness of an emerging infectious disease: evidence from
human infections with avian influenza A H7N9 in Zhejiang, China.
AB - OBJECTIVES: The aim of this study was to assess cyber-user awareness of human
infections with avian influenza A H7N9 in Zhejiang, China. METHODS: Daily Baidu
index values were compared for different keywords, different periods (epidemic
and non-epidemic), different levels of epidemic publicity (whether new cases were
publicized), and different cities (divided into high, medium, low, and zero
groups according to the number of cases). Furthermore, the correlation between
the daily Baidu index values and the daily number of new cases was analyzed.
RESULTS: Three epidemic periods (periods A/C/E) and three non-epidemic periods
(periods B/D/F) were identified from April 2013 to May 2015 according to the
curves of daily new cases. Each epidemic period was followed by a non-epidemic
period. Baidu index values using 'H7N9' as a keyword were higher than the values
using the keyword '' (avian influenza in Chinese) in earlier periods, but the
situation reversed in later periods. Index values for 'H7N9' in the epidemic
periods were higher than in the non-epidemic periods. In the first epidemic
period (period A), the Baidu index values for 'H7N9' showed no difference between
the different levels of epidemic publicity and had no correlation with the daily
number of new cases. The index values in cities without reported cases showed no
difference from the values recorded in the medium and low groups. However, a
difference and a correlation were found in a later epidemic period. CONCLUSIONS:
The Baidu index would be a useful tool for assessing cyber-user awareness of an
emerging infectious disease.
PMID- 26432410
TI - Conservation of nucleotide sequences for molecular diagnosis of Middle East
respiratory syndrome coronavirus, 2015.
AB - Infection due to the Middle East respiratory syndrome coronavirus (MERS-CoV) is
widespread. The present study was performed to assess the protocols used for the
molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses
detected between 2012 and 2015, including sequences from the large outbreak in
eastern Asia in 2015. Although the diagnostic protocols were established only 2
years ago, mismatches between the sequences of primers/probes and viruses were
found for several of the assays. Such mismatches could lead to a lower
sensitivity of the assay, thereby leading to false-negative diagnosis. A slight
modification in the primer design is suggested. Protocols for the molecular
diagnosis of viral infections should be reviewed regularly after they are
established, particularly for viruses that pose a great threat to public health
such as MERS-CoV.
PMID- 26432411
TI - Prevalence of type 2 diabetes and its association with measures of body
composition among African residents in the Netherlands--The HELIUS study.
AB - AIMS: To compare type 2 diabetes prevalence among three ethnic groups resident in
the Netherlands: Ghanaians, African Surinamese and Dutch origin. Secondly, to
determine the contribution of measures of body composition to ethnic differences
in type 2 diabetes. METHODS: Baseline data from Ghanaian (n=1873), African
Surinamese (n=2189) and Dutch (n=2151) origin participants of the HELIUS study
(aged 18-70 years) were analyzed. Type 2 diabetes was determined according to the
WHO criteria. Logistic regression tested ethnic differences in type 2 diabetes
and the contribution of body fat percentage and waist-to-hip ratio. RESULTS:
Among men, type 2 diabetes prevalence was higher in Ghanaians (14.9%) than in
African Surinamese (10.4%) and Dutch (5.0%). Among women, type 2 diabetes
prevalence in Ghanaian (11.1%) was higher than in Dutch (2.3%), but similar to
African Surinamese (11.5%). After adjusting for age, body fat percentage and
waist-to-hip ratio, the odds ratios for having type 2 diabetes were 1.55 (95% CI:
1.12-2.15) for Ghanaian men compared with African Surinamese and 4.19 (95% CI:
2.86-6.12) compared with Dutch. Among women these odds ratios were 0.94 (95% CI:
0.70-1.26) and 4.78 (95% CI: 2.82-8.11). CONCLUSIONS: The higher prevalence of
type 2 diabetes among Ghanaian compared with African Surinamese men suggests a
need to distinguish between African descent populations when assessing their type
2 diabetes risk. The higher odds for type 2 diabetes among Ghanaians cannot be
attributed to differences in body composition. Further research on the
contribution of lifestyle factors as well as genetic and epigenetic factors is
needed to identify the reasons for the observed disparities.
PMID- 26432414
TI - Technique determinants of knee abduction moments during pivoting in female soccer
players.
AB - BACKGROUND: No previous studies have investigated the optimal technique for
pivoting with regard to reducing peak knee abduction moments and potential knee
injury risk. The aim of this study was to investigate the relationships between
technique characteristics and peak knee abduction moments during pivoting.
METHODS: Twenty-seven female soccer players [mean (SD); age: 21 (3.8) years,
height: 1.67 (0.07) m, and mass: 60.0 (7.2) kg] participated in the study. Three
dimensional motion analyses of pivots on the right leg were performed using 10
Qualysis 'Pro reflex' infrared cameras (240Hz). Ground reaction forces were
collected from two AMTI force platforms (1200Hz) embedded into the running track
to examine penultimate and final contact. Pearson's correlation coefficients, co
efficients of determination and stepwise multiple regression were used to explore
relationships between a range of technique parameters and peak knee abduction
moments. Significance was set at P<0.05. FINDINGS: Stepwise multiple regression
found that initial foot progression and initial knee abduction angles together
could explain 35% (30% adjusted) of the variation in peak knee abduction moments
(F(2,26)=6.499, P=0.006). INTERPRETATION: The results of the present study
suggest that initial-foot progression and knee abduction angles are potential
technique factors to lower knee abduction moments during pivoting.
PMID- 26432413
TI - Crystallographic phasing from weak anomalous signals.
AB - The exploitation of anomalous signals for biological structural solution is
maturing. Single-wavelength anomalous diffraction (SAD) is dominant in de novo
structure analysis. Nevertheless, for challenging structures where the resolution
is low (dmin>=3.5A) or where only lighter atoms (Z<=20) are present, as for
native macromolecules, solved SAD structures are still scarce. With the recent
rapid development in crystal handling, beamline instrumentation, optimization of
data collection strategies, use of multiple crystals and structure determination
technologies, the weak anomalous diffraction signals are now robustly measured
and should be used for routine SAD structure determination. The review covers
these recent advances on weak anomalous signals measurement, analysis and
utilization.
PMID- 26432415
TI - Hip kinematics and kinetics in persons with and without cam femoroacetabular
impingement during a deep squat task.
AB - BACKGROUND: Previous studies have indicated that hip and pelvis kinematics may be
altered during functional tasks in persons with femoroacetabular impingement. The
purpose of this study was to compare hip and pelvis kinematics and kinetics
during a deep squat task between persons with cam femoroacetabular impingement
and pain-free controls. METHODS: Fifteen persons with cam femoroacetabular
impingement and 15 persons without cam femoroacetabular impingement performed a
deep squat task. Peak hip flexion, abduction, and internal rotation, and mean hip
extensor, adductor, and external rotator moments were quantified. Independent t
tests (alpha<0.05) were used to evaluate between group differences. FINDINGS:
Compared to the control group, persons with cam femoroacetabular impingement
demonstrated decreased peak hip internal rotation (15.2 degrees (SD 9.5 degrees
) vs. 9.4 degrees (SD 7.8 degrees ); P=0.041) and decreased mean hip extensor
moments (0.56 (SD 0.12) Nm/kg vs. 0.45 (SD 0.15) Nm/kg; P=0.018). In addition
persons in the cam femoroacetabular impingement group demonstrated decreased
posterior pelvis tilt during squat descent compared to the control group,
resulting in a more anteriorly tilted pelvis at the time peak hip flexion (12.5
degrees (SD 17.1 degrees ) vs. 23.0 degrees (SD 12.4 degrees ); P=0.024).
INTERPRETATION: The decreased hip internal rotation observed in persons with cam
femoroacetabular impingement may be the result of bony impingement. Furthermore,
the decrease in posterior pelvis tilt may contribute to impingement by further
approximating the femoral head-neck junction with the acetabulum. Additionally,
decreased hip extensor moments suggest that diminished hip extensor muscle
activity may contribute to decreased posterior pelvis tilt.
PMID- 26432412
TI - High burden of prediabetes and diabetes in three large cities in South Asia: The
Center for cArdio-metabolic Risk Reduction in South Asia (CARRS) Study.
AB - AIM: To estimate the prevalence of, and assess factors associated with, diabetes
and prediabetes in three South Asian cities. METHODS: Using a multi-stage cluster
random sample representative of each city, 16,288 subjects aged >=20 years
(Chennai: 6906, Delhi: 5365 and Karachi: 4017) were recruited to the Centre for
cArdio-metabolic Risk Reduction in South-Asia (CARRS) Study. Fasting plasma
glucose (FPG) and glycosylated hemoglobin (HbA1c) were measured in 13720
subjects. Prediabetes was defined as FPG 100-125 mg/dl (5.6-6.9 mmol/l) and/or
HbA1c 5.7-6.4% (39-46 mmol/mol) and diabetes as self-report and/or drug treatment
for diabetes and/or FPG>=126 mg/dl (>=7.0 mmol/l) and/or HbA1c>=6.5% (48
mmol/mol). We assessed factors associated with diabetes and prediabetes using
polytomous logistic regression models. RESULTS: Overall 47.3-73.1% of the
population had either diabetes or prediabetes: Chennai 60.7% [95%CI: 59.0-62.4%]
(diabetes - 22.8% [21.5-24.1%], prediabetes - 37.9% [36.1-39.7%]); Delhi 72.7%
[70.6-74.9%] (diabetes - 25.2% [23.6-26.8%], prediabetes - 47.6% [45.6-49.5%]);
and Karachi 47.4% [45.7-49.1%]; (diabetes - 16.3% [15.2-17.3%], prediabetes -
31.1% [29.5-32.8%], respectively). Proportions of self-reported diabetes were
55.1%, 39.0%, and 48.0% in Chennai, Delhi, and Karachi, respectively. City, age,
family history of diabetes, generalized obesity, abdominal obesity, body fat,
high cholesterol, high triglyceride, and low HDL cholesterol levels were each
independently associated with prediabetes, while the same factors plus waist-to
height ratio and hypertension were associated with diabetes. CONCLUSION: Six in
ten adults in large South Asian cities have either diabetes or prediabetes. These
data call for urgent action to prevent diabetes in South Asia.
PMID- 26432416
TI - Variations in trunk muscle activities and spinal loads following posterior lumbar
surgery: A combined in vivo and modeling investigation.
AB - BACKGROUND: Iatrogenic injuries to paraspinal muscles during posterior lumbar
surgery cause a reduction in their contractile cross-sectional area and thus
presumably their postoperative activation. This study investigates the effect of
such intraoperative injuries on postoperative patterns of muscle activations and
spinal loads during various activities using a combined modeling and in vivo MR
imaging approach. METHODS: A three-dimensional, multi-joint, musculoskeletal
model was used to estimate pre- and postoperative muscle forces and spinal loads
under various activities in upright and flexed postures. According to our in vivo
pre- and postoperative (~6 months) measurements in six patients using a 3-Tesla
MR scanner, physiological cross-sectional areas of multifidus and erector spinae
were reduced in the postoperative model by 26 and 11%, respectively. FINDINGS:
Postoperative trunk extension strength was predicted to decrease by ~23% from 215
Nm in the intact model to 165 Nm in the postoperative model. Postoperative force
in multifidus fascicles decreased by ~21-40% in flexion tasks and by ~14-35% in
upright tasks. In contrast, the sum of the forces in all other intact and less
injured extensor muscles slightly increased (by <6%) in the postoperative model.
Postoperative L5-S1 compressive and shear loads varied slightly (by ~3%).
INTERPRETATION: Intraoperative injuries induced a shift in load-sharing from the
most injured muscle (multifidus) toward other less injured and intact muscles
during all simulated activities. Postoperative rehabilitation programs should
therefore strengthen and facilitate (while avoiding muscle imbalance) not only
the injured multifidus but also other intact and less injured trunk muscles that
play a compensatory role after the operation.
PMID- 26432417
TI - Prevalence and causes of reduced visual acuity among children aged three to six
years in a metropolis in China.
AB - PURPOSE: To determine the prevalence and possible causes for reduced visual
acuity (VA) in preschool children in a metropolis in China. METHODS: A school
based paediatric eye survey including 5862 preschool children aged three to 6
years was conducted from 2011 to 2012 in Yuhuatai District, Nanjing, China, using
an age-stratified random sampling procedure. Clinical examinations including
ocular alignment, ocular motility, visual acuity, prism cover test, cycloplegic
refraction, stereopsis screening, slit lamp examination and fundus examination
were performed by trained study ophthalmologists and optometrists. Reduced VA was
defined as presenting VA of worse than 0.30 logMAR (Snellen 6/12 or 20/40), for
both better and worse eyes. RESULTS: 5667 (94.8%) children with complete VA data
were included in the data analyses. Among them, 208 and 93 had reduced VA in the
worse and better eye, respectively. Reduced VA was detected in 3.7% (95%
confidence interval [CI] 3.2%-4.2%) in the worse eye and 1.6% (95% CI 1.3%-2.0%)
in the better eye. No significant age and gender differences in reduced VA were
observed (p > 0.05). Refractive errors and amblyopia were the principal causes
for reduced VA in the worse eye which accounted for 66.8% and 32.7% of the total
cases with reduced VA, respectively. Astigmatism and hyperopia were the major
types of refractive errors causing reduced VA. CONCLUSIONS: The burden of reduced
VA in preschool children in China was similar to that of Asian children of
similar ages in the United States. Uncorrected refractive error and amblyopia
were the principal causes for reduced VA among preschoolers (aged three to 6
years) in China.
PMID- 26432418
TI - Combining C6 and C5 sugar metabolism for enhancing microbial bioconversion.
AB - Mixed sugars, which are often obtained from renewable biomass, can be converted
into biofuels and chemicals by microbial conversion. This sustainable production
process can also mitigate man-made climate change when used to petroleum-based
fuel and chemical production. In contrast to single sugar fermentations, such as
corn-based or sugarcane-based ethanol fermentations, mixed sugar fermentations
present significant challenges for cost-effective production of the target
products. In particular, inefficient and slow microbial fermentation of non
glucose sugars, such as galactose and xylose from the depolymerization of marine
and terrestrial biomass has been a major obstacle. Nonetheless, simultaneous
utilization of mixed sugars has recently been demonstrated through innovative
metabolic engineering strategies and the discovery of transporters, and metabolic
pathways which are necessary for co-fermenting glucose and non-glucose sugars.
PMID- 26432419
TI - Transforming somatic mutations of mammalian target of rapamycin kinase in human
cancer.
AB - Mammalian target of rapamycin (mTOR) is a serine-threonine kinase that acts
downstream of the phosphatidylinositol 3-kinase signaling pathway and regulates a
wide range of cellular functions including transcription, translation,
proliferation, apoptosis, and autophagy. Whereas genetic alterations that result
in mTOR activation are frequently present in human cancers, whether the mTOR gene
itself becomes an oncogene through somatic mutation has remained unclear. We have
now identified a somatic non-synonymous mutation of mTOR that results in a
leucine-to-valine substitution at amino acid position 2209 in a specimen of large
cell neuroendocrine carcinoma. The mTOR(L2209V) mutant manifested marked
transforming potential in a focus formation assay with mouse 3T3 fibroblasts, and
it induced the phosphorylation of p70 S6 kinase, S6 ribosomal protein, and
eukaryotic translation initiation factor 4E-binding protein 1 in these cells.
Examination of additional tumor specimens as well as public and in-house
databases of cancer genome mutations identified another 28 independent non
synonymous mutations of mTOR in various cancer types, with 12 of these mutations
also showing transforming ability. Most of these oncogenic mutations cluster at
the interface between the kinase domain and the FAT (FRAP, ATM, TRRAP) domain in
the 3-D structure of mTOR. Transforming mTOR mutants were also found to promote
3T3 cell survival, and their oncogenic activity was sensitive to rapamycin. Our
data thus show that mTOR acquires transforming activity through genetic changes
in cancer, and they suggest that such tumors may be candidates for molecularly
targeted therapy with mTOR inhibitors.
PMID- 26432422
TI - The importance of teaching neuroscience to psychiatric residents in the context
of psychological formulations.
PMID- 26432420
TI - Reduced Brain Cannabinoid Receptor Availability in Schizophrenia.
AB - BACKGROUND: Several lines of evidence suggest the presence of abnormalities in
the endocannabinoid (eCB) system in schizophrenia (SCZ). However, there are
limited in vivo measures of the eCB system in SCZ. METHODS: Twenty five male SCZ
subjects (SCZs) (18 antipsychotic treated and 7 antipsychotic free) were compared
with 18 age-matched male healthy control subjects (HCs). Subjects underwent one
positron emission tomography scan each with the cannabinoid receptor-1 (CB1R)
selective radiotracer [(11)C]OMAR on the high resolution research tomography
scanner. Regional volume of distribution (VT) values were determined using
kinetic modeling of positron emission tomography data as a measure of CB1R
availability. Group differences in mean composite [(11)C]OMAR VT values were
compared between SCZs and HCs. Exploratory comparisons of CB1R availability
within 15 brain regions were also conducted. All analyses were covaried for age
and body mass index. RESULTS: SCZs showed significantly (p = .02) lower composite
[(11)C]OMAR VT relative to HCs (~12% difference, effect size d = .73).
[(11)C]OMAR VT was significantly (all ps < .05) lower in SCZs in the amygdala,
caudate, posterior cingulate cortex, hippocampus, hypothalamus, and insula.
Composite [11]OMAR VT was HCs > antipsychotic treated SZCs > antipsychotic free
SZCs. Furthermore, composite [(11)C]OMAR VT was greater in HCs than SCZ smokers
(n = 11) and SCZ nonsmokers (n = 14). CONCLUSIONS: CB1R availability is lower in
male SCZ subjects compared with HCs. Furthermore, antipsychotics and tobacco use
may increase CB1R availability in this population. The findings of the study
provide further evidence supporting the hypothesis that alterations in the eCB
system might contribute to the pathophysiology of SCZ.
PMID- 26432421
TI - Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor
and neurofibroma from a patient with neurofibromatosis type 1.
AB - Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by the
development of multiple neurofibromas, cafe-au-lait spots, and Lisch nodules.
Individuals with NF1 are at increased risk of developing various tumors, such as
malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, leukemia,
glioma, rhabdomyosarcoma, and breast cancer. Here, we describe the exome
sequencing of breast cancer, MPNST, and neurofibroma from a patient with NF1. We
identified a germline mutation in the NF1 gene which resulted in conversion of
leucine to proline at amino acid position 847. In addition, we showed independent
somatic NF1 mutations in all the three tumors (frameshift insertion in breast
cancer (p.A985fs), missense mutation in MPNST (p.G23R), and inframe deletion in
dermal neurofibroma (p.L1876del-Inf)), indicating that a second hit in NF1
resulting in the loss of function could be important for tumor formation. Each
tumor had a distinct genomic profile with mutually exclusive mutations in
different genes. Copy number analysis revealed multiple copy number alterations
in the breast cancer and the MPNST, but not the benign neurofibroma. Germline
loss of chromosome 6q22.33, which harbors two potential tumor suppressor genes,
PTPRK and LAMA2, was also identified; this may increase tumor predisposition
further. In the background of NF1 syndrome, although second-hit NF1 mutation is
critical in tumorigenesis, different additional mutations are required to drive
the formation of different tumors.
PMID- 26432423
TI - An Elderly Man from Solukhumbu, Nepal, with a Rash.
PMID- 26432424
TI - In Reply to Dr Lankford.
PMID- 26432425
TI - Marked Hypofibrinogenemia and Gastrointestinal Bleeding After Copperhead
(Agkistrodon contortrix) Envenomation.
AB - Compared with other crotaline envenomations, copperhead envenomations have
historically been reported as having less severe hematologic venom effects and
rarely hemorrhage. We report a case of clinically significant gastrointestinal
bleeding after a copperhead (Agkistrodon contortrix) envenomation. A 52-year-old
woman with a history of systemic lupus erythematosus was bitten on her right
medial ankle after which hypofibrinogenemia and hematochezia developed. The
symptoms resolved after repeated administration of Crotalidae polyvalent immune
Fab (ovine) antivenom. She was discharged without further complications 2 days
later. Although copperhead envenomations are classically considered less severe
than other crotaline envenomations, this case demonstrates the potential of the
venom to produce clinically significant hematologic effects.
PMID- 26432426
TI - Predictive Factors for Determining the Clinical Severity of Pediatric Scorpion
Envenomation Cases in Southeastern Turkey.
AB - OBJECTIVE: The aim of this study was to define the epidemiological, clinical, and
laboratory manifestations of scorpion envenomation and to identify factors that
are predictive of severe cases. METHODS: The medical files of 41 scorpion
envenomation cases were reviewed retrospectively. The cases were classified as
mild-moderate or severe. The epidemiological, clinical, and laboratory findings
of patients were recorded. RESULTS: There were 27 patients (65.9%) in the mild
moderate group and 14 patients (34.1%) in the severe group. The median age of all
patients was 48 months. The most common systemic finding was cold extremities
(41.5%). In all patients, the most commonly observed dysrhythmia was sinus
tachycardia (34.1%). Two patients (4.9%) had pulseless ventricular tachycardia
and died. Pulmonary edema and myocarditis were observed in 9 patients (22%).
Median values of leukocyte and glucose levels were markedly increased in the
severe group. Additionally, the mean thrombocyte level (540,857 +/- 115,261
cells/mm(3)) in the severe group was significantly increased compared with the
mild-moderate group (391,365 +/- 150,017 cells/mm(3)). Thrombocyte levels
exhibited a positive correlation with leukocyte and glucose values and a negative
correlation with patient left ventricular ejection fraction. Multivariate
analysis of laboratory parameters indicated that the most predictive factor for
clinical severity is thrombocytosis (odds ratio 23.9; 95% CI: 1.6-353.5, P =
.021). CONCLUSIONS: Although our results share some similarities with those of
other reports, thrombocytosis was markedly increased in the severe group and
served as the most predictive laboratory factor of clinical severity.
PMID- 26432427
TI - Brown Bear Attacks in a Nepalese Scenario: A Brief Review.
PMID- 26432428
TI - In Response to Snakebite Rebound Coagulopathy by Witham et al.
PMID- 26432429
TI - New aspects of the clinicopathological features and treatment of mycosis
fungoides and Sezary syndrome.
AB - Mycosis fungoides and Sezary syndrome are T-helper (Th)2-skewed cutaneous
lymphomas. The clinical course of mycosis fungoides is classically indolent,
manifesting as patches, plaques and tumors. Along with their progression, Th2
dominance tends to be accelerated. In this review, we discuss the epidemiology,
clinicopathogenetic features and therapeutic approaches in mycosis fungoides and
Sezary syndrome.
PMID- 26432430
TI - Efficacy of Intra-articular Platelet-Rich Plasma Injections in Knee
Osteoarthritis: A Systematic Review.
AB - PURPOSE: To determine (1) whether platelet-rich plasma (PRP) injection
significantly improves validated patient-reported outcomes in patients with
symptomatic knee osteoarthritis (OA) at 6 and 12 months postinjection, (2)
differences in outcomes between PRP and corticosteroid injections or
viscosupplementation or placebo injections at 6 and 12 months postinjection, and
(3) similarities and differences in outcomes based on the PRP formulations used
in the analyzed studies. METHODS: PubMed, Cochrane Central Register of Controlled
Trials, SCOPUS, and Sport Discus were searched for English-language, level I
evidence, human in vivo studies on the treatment of symptomatic knee OA with
intra-articular PRP compared with other options, with a minimum of 6 months of
follow-up. A quality assessment of all articles was performed using the Modified
Coleman Methodology Score (average, 83.3/100), and outcomes were analyzed using 2
proportion z-tests. RESULTS: Six articles (739 patients, 817 knees, 39% males,
mean age of 59.9 years, with 38 weeks average follow-up) were analyzed. All
studies met minimal clinical important difference criteria and showed significant
improvements in statistical and clinical outcomes, including pain, physical
function, and stiffness, with PRP. All but one study showed significant
differences in clinical outcomes between PRP and hyaluronic acid (HA) or PRP and
placebo in pain and function. Average pretreatment Western Ontario and McMaster
Universities Osteoarthritis Index (WOMAC) scores were 52.36 and 52.05 for the PRP
and HA groups, respectively (P = .420). Mean post-treatment WOMAC scores for PRP
were significantly better than for HA at 3 to 6 months (28.5 and 43.4,
respectively; P = .0008) and at 6 to 12 months (22.8 and 38.1, respectively; P =
.0062). None of the included studies used corticosteroids. CONCLUSIONS: In
patients with symptomatic knee OA, PRP injection results in significant clinical
improvements up to 12 months postinjection. Clinical outcomes and WOMAC scores
are significantly better after PRP versus HA at 3 to 12 months postinjection.
There is limited evidence for comparing leukocyte-rich versus leukocyte-poor PRP
or PRP versus steroids in this study. LEVEL OF EVIDENCE: Level I, systematic
review of Level I studies.
PMID- 26432431
TI - Poor Agreement on Classification and Treatment of Subscapularis Tendon Tears.
AB - PURPOSE: To assess the inter- and intraobserver agreement for classification and
management of subscapularis tendon pathology based on arthroscopy and magnetic
resonance imaging (MRI). METHODS: Twenty-two orthopaedic surgeons from the
Multicenter Orthopaedic Outcomes Network (MOON) shoulder group reviewed still
arthroscopic and MRI images of the subscapularis tendon from patients with a
random assortment of subscapularis morphology. The surgeons were asked to
classify the pathology based on 2 systems (Lafosse and Lyons) and choose whether
they would repair the tendon and, if so, the method of repair (open or
arthroscopic). The survey was administered 3 times to each surgeon. Inter- and
intraobserver reliability between testing rounds was determined by kappa
analysis. RESULTS: Interobserver reliability on classification of tears was poor
based on MRI (k = 0.18 to 0.19) and fair based on arthroscopy (k = 0.26 to 0.29).
Interobserver agreement on whether surgical treatment was indicated was fair for
both MRI (k = 0.28) and arthroscopy (k = 0.38), while the agreement for type of
surgery was poor based on MRI (k = 0.18) and fair based on arthroscopy (k =
0.28). Interobserver agreement did not improve when both MRI and arthroscopy were
provided simultaneously (k = 0.24 to 0.30). Intraobserver reliability for
classification and treatment was fair to moderate for both MRI (k = 0.32 to 0.50)
and arthroscopic imaging (k = 0.39 to 0.56). When considering just those patients
with normal tendons, surgeon agreement improved. For all questions, the
arthroscopic images had a higher level of agreement among surgeons than the MRI
(P < .001). CONCLUSIONS: Although surgeons tended to have higher reliability when
presented with arthroscopic images compared with MRI, there was very little
agreement on the classification and management of subscapularis tendon tears.
PMID- 26432432
TI - Efficacy of Nonsteroidal Anti-inflammatory Drug Prophylaxis for Heterotrophic
Ossification in Hip Arthroscopy: A Systematic Review.
AB - PURPOSE: The purpose of this systematic review was to investigate the efficacy of
nonsteroidal anti-inflammatory drug (NSAID) prophylaxis for preventing
heterotopic ossification (HO) in the setting of hip arthroscopy. METHODS: A
systematic search was performed in duplicate for studies comparing the use of
NSAID prophylaxis for HO in the setting of hip arthroscopy until March 2015.
Study parameters--including sample size, incidence of HO, adverse effects, and
level of symptoms--were obtained. Furthermore, the level of evidence of studies
was collected and quality assessment was performed. The difference in incidence
as well as pooled odds ratios were calculated and analyzed to compare no
prophylaxis versus NSAID prophylaxis. RESULTS: This systematic review identified
5 studies, consisting of 1,662 patients, investigating NSAID prophylaxis in hip
arthroscopy. HO was diagnosed with the use of postoperative hip radiographs at
follow-up, with 95% of cases classified using the Brooker classification. The
incidence of HO was 13.4% without NSAID prophylaxis and 3.3% with NSAID
prophylaxis. Pooled odds ratios from the prospective studies were 0.07 (95%
confidence interval [CI], 0.02 to 0.28; P = .0002; I(2) = 0%), showing with
statistical significance that NSAID prophylaxis decreased the incidence of HO.
The retrospective data similarly showed pooled odds ratios of 0.03 (95% CI, 0.00
to 1.43); P = .08; I(2) = 84%), although it was not statistically significant.
Most of the patients who experienced HO in both groups were not reported to be
symptomatic. Adverse effects and compliance were not consistently reported.
CONCLUSIONS: The available orthopaedic literature suggests that the incidence of
postoperative HO may be decreased with the use of NSAID prophylaxis in hip
arthroscopy. However, the evidence is unclear regarding NSAID drug regimen
choice, drug compliance, and adverse effects. LEVEL OF EVIDENCE: Level III,
systematic review of Level I, Level II, and Level III studies.
PMID- 26432433
TI - Preoperative platelet-lymphocyte ratio is superior to neutrophil-lymphocyte ratio
as a prognostic factor for soft-tissue sarcoma.
AB - BACKGROUND: Inflammation can promote tumor growth, invasion, angiogenesis and
even metastasis. Inflammatory markers have been identified as prognostic
indicators in various malignances. This study compared the usefulness of platelet
lymphocyte ratio (PLR) with that of neutrophil-lymphocyte ratio (NLR) for
predicting outcomes of patients who underwent radical resection for soft tissue
sarcoma (STS). METHODS: We included 222 STS patients in this retrospective study.
Kaplan-Meier curves and multivariate Cox proportional models were used to
calculate overall survival (OS) and disease free survival (DFS). RESULTS: In
univariate analysis, elevated PLR and NLR were both significantly associated with
decreased OS. In multivariate analysis, PLR (HR: 2.60; 95 % CI: 1.17-5.74, P =
0.019) but not NLR was still identified as independent predictors of outcome.
Median OS was 62 and 76 months for the high PLR and low PLR groups, respectively.
High PLR and NLR were both significantly associated with shorter DFS in
univariate analysis, with median DFS of 18 and 57 months in the high PLR and low
PLR groups. In multivariate analysis, elevated PLR (HR: 1.77; 95 % CI: 1.05-2.97,
P = 0.032) was also related to decreased DFS. DISCUSSION: Our findings provide a
new and valuable clue for diagnosing and monitoring STS. Prediction of disease
progression is not only determined by the use of clinical or histopathological
factors including tumor grade, tumor size, and tumor site but also by host
response factors such as performance status, weight loss, and systemic
inflammatory response. They also significantly affect clinical outcomes. Thus,
PLR can be used to enhance clinical prognostication. Furthermore, the PLR can be
assessed from peripheral blood tests that are routinely available without any
other complicated expenditure, thus providing lower cost and greater convenience
for the prognostication. CONCLUSION: Elevated preoperative PLR as an independent
prognostic factor is superior to NLR in predicting clinical outcome in patients
with STS.
PMID- 26432434
TI - Primary side control of load voltage for transcutaneous energy transmission.
AB - Transcutaneous energy transmission (TET) is considered as a good way to
wirelessly power the implanted devices in human bodies. The load voltage provided
from the TET to the implanted device should be kept stable to ensure the device
working well, which however, is easily affected by the required power variation
for different body movements and coil-couple malposition accompanying skin
peristalsis. Commonly, the load voltage applied onto the device should be
measured and feedback for power is regulated by implanting sensing and
communication units into the body, which causes additional energy cost, increased
size and weight of the implanted device. This paper takes the TET for artificial
heart as an example to propose a novel primary side control method of the load
voltage for TET, which does not require any additional implanted components. In
the method, sensing coils are used to measure the malposition between the
transmitter coil (TC) and receiver coil, and the magnitude of the TC current
outside the human body. The measurement results are used to estimate the load
voltage inside the body through calculation, whose value provide a base to
develop a PI control system to regulate the input power of TET for the load
voltage stability. The proposed method is experimentally validated on an actual
TET for artificial heart by varying its load in a wide range under serious coil
couple malposition. With applying the primary side control, the variation of the
load voltage is reduced to only 25 % of that without the control.
PMID- 26432435
TI - The structure and mechanical properties of articular cartilage are highly
resilient towards transient dehydration.
AB - Articular cartilage is a mechanically highly challenged material with very
limited regenerative ability. In contrast to elastic cartilage, articular
cartilage is exposed to recurring partial dehydration owing to ongoing
compression but maintains its functionality over decades. To extend our current
understanding of the material properties of articular cartilage, specifically the
interaction between the fluid and solid phase, we here analyze the reversibility
of tissue dehydration. We perform an artificial dehydration that extends beyond
naturally occurring levels and quantify material recovery as a function of the
ionic strength of the rehydration buffer. Mechanical (indentation, compression,
shear, and friction) measurements are used to evaluate the influence of de- and
rehydration on the viscoelastic properties of cartilage. The structure and
composition of native and de/rehydrated cartilage are analyzed using histology,
scanning electron microscopy, and atomic force microscopy along with a 1,9
dimethylmethylene blue (DMMB) assay. A broad range of mechanical and structural
properties of cartilage can be restored after de- and rehydration provided that a
physiological salt solution is used for rehydration. We detect only minor
alterations in the microarchitecture of rehydrated cartilage in the superficial
zone and find that these alterations do not interfere with the viscoelastic and
tribological properties of the tissue. STATEMENT OF SIGNIFICANCE: We here
demonstrate the sturdiness of articular cartilage towards changes in fluid
content and show that articular cartilage recovers a broad range of its material
properties after dehydration. We analyze the reversibility of tissue dehydration
to extend our current understanding of how the material properties of cartilage
are established, focusing on the interaction between the fluid and solid phase.
Our findings suggest that the high resilience of the tissue minimizes the risk of
irreversible material failure and thus compensates, at least in part, its poor
regenerative abilities. Tissue engineering approaches should thus not only
reproduce the correct tissue mechanics but also its pronounced sturdiness to
guarantee a similar longevity.
PMID- 26432437
TI - Modulation of the gene expression of annulus fibrosus-derived stem cells using
poly(ether carbonate urethane)urea scaffolds of tunable elasticity.
AB - Annulus fibrosus (AF) injuries commonly lead to substantial deterioration of the
intervertebral disc (IVD). While tissue engineering has recently evolved into a
promising approach for AF regeneration, it remains challenging due to the
cellular, biochemical, and mechanical heterogeneity of AF tissue. In this study,
we explored the use of AF-derived stem cells (AFSCs) to achieve diversified
differentiation of cells for AF tissue engineering. Since the differentiation of
stem cells relies significantly on the elasticity of the substrate, we
synthesized a series of biodegradable poly(ether carbonate urethane)urea (PECUU)
materials whose elasticity approximated that of native AF tissue. When AFSCs were
cultured on electrospun PECUU fibrous scaffolds, the gene expression of collagen
I in the cells increased with the elasticity of scaffold material, whereas the
expression of collagen-II and aggrecan genes showed an opposite trend. At the
protein level, the content of collagen-I gradually increased with substrate
elasticity, while collagen-II and GAG contents decreased. In addition, the cell
traction forces (CTFs) of AFSCs gradually decreased with scaffold elasticity.
Such substrate elasticity-dependent changes of AFSCs were similar to the gradual
transition in the genetic, biochemical, and biomechanical characteristics of
cells from inner to outer regions of native AF tissue. Together, findings from
this study indicate that AFSCs, depending on the substrate elasticity, have
strong tendencies to differentiate into various types of AF-like cells, thereby
providing a solid foundation for the tissue engineering applications of AFSCs.
STATEMENT OF SIGNIFICANCE: Repairing the annulus fibrosus (AF) of intervertebral
disc (IVD) is critical for the treatment of disc degeneration disease, but
remains challenging due to the significant heterogeneity of AF tissue.
Previously, we have identified rabbit AF-derived stem cells (AFSCs), which are AF
tissue-specific and hold promise for AF regeneration. In this study, we
synthesized a series of poly(ether carbonate urethane)ureas of various elasticity
(or stiffness) and explored the potential of induced differentiation of AFSCs
using electrospun PECUU scaffolds. This work has, for the first time, found that
AFSCs are able to present different gene expression patterns simply as a result
of the elasticity of scaffold material. Therefore, our findings will help
supplement current knowledge of AF tissue regeneration and may benefit a
diversified readership from scientific, engineering, and clinical settings whose
work involves the biology and tissue engineering of IVD.
PMID- 26432436
TI - Tumor mitochondria-targeted photodynamic therapy with a translocator protein
(TSPO)-specific photosensitizer.
AB - Photodynamic therapy (PDT) has been proven to be a minimally invasive and
effective therapeutic strategy for cancer treatment. It can be used alone or as a
complement to conventional cancer treatments, such as surgical debulking and
chemotherapy. The mitochondrion is an attractive target for developing novel PDT
agents, as it produces energy for cells and regulates apoptosis. Current strategy
of mitochondria targeting is mainly focused on utilizing cationic
photosensitizers that bind to the negatively charged mitochondria membrane.
However, such an approach is lack of selectivity of tumor cells. To minimize the
damage on healthy tissues and improve therapeutic efficacy, an alternative
targeting strategy with high tumor specificity is in critical need. Herein, we
report a tumor mitochondria-specific PDT agent, IR700DX-6T, which targets the
18kDa mitochondrial translocator protein (TSPO). IR700DX-6T induced apoptotic
cell death in TSPO-positive breast cancer cells (MDA-MB-231) but not TSPO
negative breast cancer cells (MCF-7). In vivo PDT study suggested that IR700DX-6T
mediated PDT significantly inhibited the growth of MDA-MB-231 tumors in a target
specific manner. These combined data suggest that this new TSPO-targeted
photosensitizer has great potential in cancer treatment. STATEMENT OF
SIGNIFICANCE: Photodynamic therapy (PDT) is an effective and minimally invasive
therapeutic technique for treating cancers. Mitochondrion is an attractive target
for developing novel PDT agents, as it produces energy to cells and regulates
apoptosis. Current mitochondria targeted photosensitizers (PSs) are based on
cationic molecules, which interact with the negatively charged mitochondria
membrane. However, such PSs are not specific for cancerous cells, which may
result in unwanted side effects. In this study, we developed a tumor mitochondria
targeted PS, IR700DX-6T, which binds to translocator protein (TSPO). This agent
effectively induced apoptosis in TSPO-positive cancer cells and significantly
inhibited tumor growth in TSPO-positive tumor-bearing mice. These combined data
suggest that IR700DX-6T could become a powerful tool in the treatment of multiple
cancers that upregulate TSPO.
PMID- 26432438
TI - A smart, phase transitional and injectable DOX/PLGA-Fe implant for magnetic
hyperthermia-induced synergistic tumor eradication.
AB - Magnetic hyperthermia ablation is a new and minimally invasive modality for
localized tumor removal. However, an inadequate ablation dosage can leave a
residual tumor or cause a variety of complications. In addition, commonly used
magnetic nanoparticles can easily escape from the tumor tissue, which present
potential safety problems. In this study, a smart phase transitional and
injectable implant based on biocompatible poly lactic-co-glycolic acid (PLGA)
implant incorporating magnetic material (Fe powder) and anti-cancer drug
(doxorubicin (DOX)) was developed. The magnetic-induced hyperthermia and release
efficiency of DOX were evaluated in vitro. Drug release can be controlled under
external alternating current magnetic field (AMF). The results of the in vivo
tumor therapeutic efficacy showed that when exposed to external AMF, this smart
injectable DOX/PLGA-Fe implant could converse magnetic energy into heat and
accelerate the release of DOX, which leads to increasing the temperature to
achieve tumor coagulative necrosis and accelerating the release of DOX to enhance
residual tumor apoptosis. Furthermore, there was no leakage of magnetic material,
as demonstrated using real-time ultrasound (US) and computerized tomography (CT)
imaging, realizing the guidance and monitoring of tumor therapy. In conclusion,
this smart phase transitional and injectable implant DOX/PLGA-Fe has the ability
to improve the efficiency of this newly developed minimally invasive magnetic
ablation of tumor treatment technique, and will provide a new avenue of
developing minimally invasive synergistic tumor therapy.
PMID- 26432439
TI - Inhibition of osteoclastogenesis through siRNA delivery with tunable mesoporous
bioactive nanocarriers.
AB - Gene silencing through siRNA delivery has shown great promise for treating
diseases and repairing damaged tissues, including bone. This report is the first
to develop siRNA delivery system in the inhibition of osteoclastic functions
which in turn can help turn-over bone mass increase in the diseases like
osteoporosis. For this reason, biocompatible and degradable nanocarriers that can
effectively load and deliver genetic molecules to target cells and tissues are
being actively sought by researchers. In this study, mesoporous bioactive glass
nanospheres (MBG), a novel unique biocompatible degradable inorganic nanocarrier,
is introduced. Furthermore, siRNA was designed to function by inhibiting the
expression of the receptor activator of nuclear factor kappa B (RANK) in order to
suppress osteoclastogenesis. Amine-functionalized MBG were synthesized with
tunable mesoporosities, showing a strong complexation with siRNA. An in vitro
release profile indicated that the siRNA from the MBG was able to achieve a
highly sustainable liberation for up to 4 days, confirming a temporary delivery
system can be designed to function for that period of time. The intracellular
uptake capacity of the complex siRNA(RANK)-MBG was recorded to be around 70%.
Furthermore, the RANK-expressing cell population declined down to 29% due to the
delivery of siRNA(RANK)-MBG (vs. 86% in control). The expression of
osteoclastogenesis-related genes, including c-fos, cathepsin-K, tartrate
resistant acid phosphatase (TRAP), and nuclear factor of activated T-cells
cytoplasmic 1 (NFATc1), was substantially down-regulated by the siRNA delivery
system. This study reports for the first time on the use of a novel MBG delivery
system for siRNA that aims to suppress osteoclastic actions. MBGs may be a
potential gene delivery platform for hard tissue repair and disease treatment due
to the collective results which indicate a high loading capacity, temporary
release kinetics, high intracellular uptake rate, and sufficient gene silencing
effects, together with the intrinsic beneficial properties like bone-bioactivity
and degradability. STATEMENT OF SIGNIFICANCE: This report is the first to develop
siRNA delivery system of biocompatible and degradable nanocarriers made from a
unique composition, i.e., mesoporous bioactive glass that can effectively load
and deliver genetic molecules to osteoclastic cells. We proved through a series
of studies that the biocompatible nanocarriers are effective for the delivery of
siRNA in the inhibition of osteoclastic functions which thus might be considered
as a nanocarrier platform to help turn-over bone mass increase in the diseases
like osteoporosis.
PMID- 26432440
TI - Osteogenic differentiation of human mesenchymal stem cells in the absence of
osteogenic supplements: A surface-roughness gradient study.
AB - The use of biomaterials to direct osteogenic differentiation of human mesenchymal
stem cells (hMSCs) in the absence of osteogenic supplements is thought to be part
of the next generation of orthopedic implants. We previously engineered surface
roughness gradients of average roughness (Ra) varying from the sub-micron to the
micrometer range (~0.5-4.7 MUm), and mean distance between peaks (RSm) gradually
varying from ~214 MUm to 33 MUm. Here we have screened the ability of such
surface-gradients of polycaprolactone to influence the expression of alkaline
phosphatase (ALP), collagen type 1 (COL1) and mineralization by hMSCs cultured in
dexamethasone (Dex)-deprived osteogenic induction medium (OIM) and in basal
growth medium (BGM). Ra~1.53 MUm/RSm~79 MUm in Dex-deprived OI medium, and
Ra~0.93 MUm/RSm~135 MUm in BGM consistently showed higher effectiveness at
supporting the expression of the osteogenic markers ALP, COL1 and mineralization,
compared to the tissue culture polystyrene (TCP) control in complete OIM. The
superior effectiveness of specific surface-roughness revealed that this strategy
may be used as a compelling alternative to soluble osteogenic inducers in
orthopedic applications featuring the clinically relevant biodegradable polymer
polycaprolactone. STATEMENT OF SIGNIFICANCE: Biodegradable polymers, such as
polycaprolactone (PCL), are promising materials in the field of tissue
engineering and regenerative medicine, which aims at creating viable options to
replace permanent orthopedic implants. The material, cells, and growth
stimulating factors are often referred to as the key components of engineered
tissues. In this article, we studied the hypothesis of specific surface
modification of PCL being capable of inducing mesenchymal stem cell
differentiation in bone cells in the absence of cell-differentiating factors. The
systematic investigation of the linearly varying surface-roughness gradient
showed that an average PCL roughness of 0.93 MUm alone can serve as a compelling
alternative to soluble osteogenic inducers in orthopedic applications featuring
the clinically relevant biodegradable polymer polycaprolactone.
PMID- 26432441
TI - Preparation, characterization, in vitro drug release, and cellular interactions
of tailored paclitaxel releasing polyethylene oxide films for drug-coated
balloons.
AB - Drug-coated balloons (DCBs) are used to treat various cardiovascular diseases.
Currently available DCBs carry drug on the balloon surface either solely or using
different carriers. Several studies have shown that a significant amount of drug
is lost in the blood stream during balloon tracking to deliver only a sub
therapeutic level of drug at the treatment site. This research is focused on
developing paclitaxel (PAT) loaded polyethylene oxide (PEO) films (PAT-PEO) as a
controlled drug delivery carrier for DCBs. An array of PAT-PEO films were
developed in this study to provide tailored release of >90% of drug only at
specific time intervals, which is the time frame required for carrying out
balloon-based therapy. The characterizations of PAT-PEO films using SEM, FTIR,
and DSC showed that the films developed were homogenous and the PAT was
molecularly dispersed in the PEO matrix. Mechanical tests showed that most PAT
PEO films developed were flexible and ductile, with yield and tensile strengths
not affected after PAT incorporation. The viability, proliferation, morphology,
and phenotype of smooth muscle cells (SMCs) interacted with control-PEO and PAT
PEO films were investigated. All control-PEO and PAT-PEO films showed a
significant inhibitory effect on the growth of SMCs, with the degree of
inhibition strongly dependent on the w/v% of the polymer used. The PAT-PEO
coating was produced on the balloons. The integrity of PAT-PEO coating was well
maintained without any mechanical defects occurring during balloon inflation or
deflation. The drug release studies showed that only 15% of the total PAT loaded
was released from the balloons within the initial 1min (typical balloon tracking
time), whereas 80% of the PAT was released between 1min and 4min (typical balloon
treatment time). Thus, this study demonstrated the use of PEO as an alternate
drug delivery system for the balloons. STATEMENT OF SIGNIFICANCE: Atherosclerosis
is primarily responsible for cardiovascular diseases (CVDs) in millions of
patients every year. Drug-coated balloons (DCBs) are commonly used to treat
various CVDs. However, in several currently used DCBs, a significant amount of
drug is lost in the blood stream during balloon tracking to deliver only a sub
therapeutic level of drug at the treatment site. In this study, paclitaxel
containing polyethylene oxide (PEO) films were developed to provide unique
advantages including drug release profiles specifically tailored for balloon
based therapy, homogeneous films with molecularly dispersed drug, flexible and
ductile films, and exhibits significant inhibitory effect on smooth muscle cell
growth. Thus, this study demonstrated the use of PEO as an alternate drug
delivery platform for DCBs to improve its efficacy.
PMID- 26432442
TI - Decellularized human placenta chorion matrix as a favorable source of small
diameter vascular grafts.
AB - Biomaterials based on decellularized tissues are increasingly attracting
attention as functional alternatives to other natural or synthetic materials.
However, a source of non-cadaver human allograft material would be favorable.
Here we establish a decellularization method of vascular tissue from
cryopreserved human placenta chorionic plate starting with an initial freeze-thaw
step followed by a series of chemical treatments applied with a custom-made
perfusion system. This novel pulsatile perfusion set-up enabled us to
successfully decellularize the vascular tissue with lower concentrations of
chemicals and shorter exposure times compared to a non-perfusion process. The
decellularization procedure described here lead to the preservation of the native
extracellular matrix architecture and the removal of cells. Quantitative analysis
revealed no significant changes in collagen content and a retained
glycosaminoglycan content of approximately 29%. In strain-to-failure tests, the
decellularized grafts showed similar mechanical behavior compared to native
controls. In addition, the mechanical values for ultimate tensile strength and
stiffness were in an acceptable range for in vivo applications. Furthermore,
biocompatibility of the decellularized tissue and its recellularizationability to
serve as an adequate substratum for upcoming recellularization strategies using
primary human umbilical vein endothelial cells (HUVECs) was demonstrated. HUVECs
cultured on the decellularized placenta vessel matrix performed
endothelialization and maintained phenotypical characteristics and cell specific
expression patterns. Overall, the decellularized human placenta vessels can be a
versatile tool for experimental studies on vascularization and as potent graft
material for future in vivo applications. STATEMENT OF SIGNIFICANCE: In the US
alone more than 1million vascular grafts are needed in clinical practice every
year. Despite severe disadvantages, such as donor site morbidity, autologous
grafting from the patient's own arteries or veins is regarded as the gold
standard for vascular tissue repair. Besides, strategies based on synthetic or
natural materials have shown limited success. Tissue engineering approaches based
on decellularized tissues are regarded as a promising alternative to clinically
used treatments to overcome the observed limitations. However, a source for
supply of non-cadaver human allograft material would be favorable. Here, we
established a decellularization method of vascular tissue from the human placenta
chorionic plate, a suitable human tissue source of consistent quality. The
decellularized human placenta vessels can be a potent graft material for future
in vivo applications and furthermore might be a versatile tool for experimental
studies on vascularization.
PMID- 26432443
TI - Gingival epithelial cells support osteoclastogenesis by producing receptor
activator of nuclear factor kappa B ligand via protein kinase A signaling.
AB - BACKGROUND AND OBJECTIVE: Periodontal disease is dental plaque-induced
inflammatory disease of the periodontal tissues that results in bone loss in the
affected teeth. During bone resorption, receptor activator of nuclear factor
kappa B ligand (RANKL) is an essential factor that regulates osteoclastogenesis.
Recently, we found that gingival epithelial cells (GECs) in periodontal tissue
produce RANKL, the expression of which is regulated by tumor necrosis factor
alpha and protein kinase A signaling. In this study, we asked whether RANKL
producing GECs induce bone marrow macrophages (BMMs) to form osteoclasts in a co
culture system. MATERIAL AND METHODS: Ca9-22 GECs and osteoclast precursor BMMs
were co-cultured with or without the protein kinase A signaling activator
forskolin or inhibitor H89 to examine whether the RANKL-producing GECs could be
induced to form osteoclasts, as determined using a pit formation assay. RESULTS:
Osteoclasts formed spontaneously in co-cultures of Ca9-22 cells and BMMs, even in
the absence of RANKL. The cells were cultured on bone slices for 14 d, at which
time resorption pits were observed. Forskolin treatment significantly increased
osteoclast numbers in these co-cultures, but forskolin alone did not induce
osteoclast formation by BMMs. CONCLUSION: GECs producing RANKL are able to
support osteoclastogenesis in an in vitro co-culture system using GECs and BMMs,
in a process promoted by forskolin.
PMID- 26432444
TI - A novel method for murine intrahepatic islet transplantation via cecal vein.
AB - Islet transplantation is one of the most beneficial treatment modality to treat
type 1 diabetic patients with frequent hypoglycemic unawareness. In clinical
setting, human islets are infused via portal vein and are settled in the end
portal venules in the liver. However, mouse islets are transplanted into kidney
subcapsule or liver through direct portal vein. These conventional
transplantation methods have several drawbacks such as different physiological
environments around the transplanted islets in kidney subcapsule from the liver
and high mortality rate in direct portal vein approach. In this study, we
introduced murine intrahepatic islet transplantation method via cecal vein to
have the same surgical operation route in humans as well as guaranteeing low
mortality rate after islet transplantation. With this protocol, consistent
normoglycemia can be obtained in diabetic mice, while keeping operation-related
mortality extremely low. This approach with easier accessibility and low
mortality will make murine intrahepatic islet transplantation a useful model for
studying immunological mechanisms such as strong innate and adaptive immune
responses that occur in human islet transplantation.
PMID- 26432445
TI - Efficacy of the FilmArray blood culture identification panel for direct molecular
diagnosis of infectious diseases from samples other than blood.
AB - Molecular-based techniques reduce the delay in diagnosing infectious diseases and
therefore contribute to better patient outcomes. We assessed the FilmArray blood
culture identification (BCID) panel (Biofire Diagnostics/bioMerieux) directly on
clinical specimens other than blood: cerebrospinal, joint, pleural and ascitic
fluids, bronchoscopy samples and abscesses. We compared the results from 88
samples obtained by culture-based techniques. The percentage of agreement between
the two methods was 75 % with a Cohen kappa value of 0.51. Global sensitivity and
specificity using the FilmArray BCID panel were 71 and 97 %, respectively.
Sensitivity was poorer in samples with a low bacterial load, such as ascitic and
pleural fluids (25 %), whereas the sensitivity for abscess samples was high (89
%). These findings suggest that the FilmArray BCID panel could be useful to
perform microbiological diagnosis directly from samples other than positive blood
cultures, as it offers acceptable sensitivity and moderate agreement with
conventional microbiological methods. Nevertheless, cost-benefit studies should
be performed before introducing this method into algorithms for microbiological
diagnostics.
PMID- 26432446
TI - Genetic structure of populations of sugarcane streak mosaic virus in China:
Comparison with the populations in India.
AB - Sugarcane streak mosaic virus (SCSMV) causes mosaic and streak symptoms on
sugarcane and sorghum crops, and has a broad host range. SCSMV is a member of the
genus Poacevirus in the family Potyviridae.Ten SCSMV isolates were collected from
sugarcane plants showing mosaic and streaking in Southern China from 2009-2011.
Sequence-based phylogenetic and population genetic analyses were conducted using
four partial genomic sequences covering the full genomes. These analyses were
used to estimate the subpopulation differentiation and divergence within the
Chinese virus population, and were compared with isolates from India. SCSMV
infected sugarcane plants in the field commonly harbor virus quasispecies (mutant
cloud), and often have mixed infections with the same virus isolates. Inter- and
intra-lineage recombination sites were identified in the protein 1, helper
component proteinase, coat protein and 3' non-coding regions of the Chinese
isolates. All the Chinese non-recombinant isolates fell into at least nine
lineages, and many clustered with Indian isolates. However, estimates of genetic
differentiation and gene flow indicated that the SCSMV populations in China and
India are genetically independent. Our genetic study of a poacevirus population
in South Asia regions indicates the importance of the evolutionary-based design
to control viruses.
PMID- 26432447
TI - Comparison of small RNA profiles in Nicotiana benthamiana and Solanum
lycopersicum infected by polygonum ringspot tospovirus reveals host-specific
responses to viral infection.
AB - Viral small RNAs (vsRNAs) are one of the key elements involved in RNA silencing
based defense against viruses in plants. We analyzed the vsRNA profiles in
Nicotiana benthamiana and Solanum lycopersicum infected by polygonum ringspot
virus (PolRSV) (Tospovirus, Bunyaviridae). VsRNAs were abundant in both hosts,
but a different size profile was observed, with an abundance peak at 21 in N.
benthamiana and at 22 nt in tomato. VsRNAs mapping to the PolRSV L genomic
segment were under-represented in both hosts, while S and M segments were
differentially and highly targeted in N. benthamiana and tomato, respectively.
Differences in preferential targeting of single ORFs were observed, with over
representation of NSs ORF-derived reads in N. benthamiana. Intergenic regions
(IGRs)-mapping vsRNAs were under-represented, while enrichment of vsRNAs reads
mapping to the NSs positive sense strand was observed in both hosts. Comparison
with a previous study on tomato spotted wilt virus (TSWV) under the same
experimental conditions, showed that the relative accumulation of PolRSV-specific
and endogenous sRNAs was similar to the one observed for silencing suppressor
deficient TSWV strains, suggesting possible different properties of PolRSV NSs
silencing suppressor compared to that of TSWV.
PMID- 26432448
TI - Intestinal Alterations, Basal Hematology, and Biochemical Parameters in
Adolescent Rats Fed Different Sources of Dietary Copper.
AB - Copper (Cu) is required for basically all biochemical and physiological processes
in the body. The aim was to evaluate the effects of different sources of dietary
copper on jejunal epithelium histomorphometry in adolescent rats. Male rats at
the age of 5 weeks were used in the 12-week experiment. The control group was fed
with standard diet providing the required Cu level (5 mg/kg body weight (bw) per
day) in an inorganic form (sulfate) covered 100 % of daily demand, and the other
three groups were supplemented with Cu-glycine complex covered 50, 75, and 100 %
daily demand. Basal hematological and plasma biochemical analyses as well as
histomorphometric examinations of the jejunal epithelium and liver were
performed. Cu given in the organic form in 100 % of daily demand depressed the
muscular and submucosa layer and the crypt depth (P < 0.05) without an influence
of the innervation of the jejunum. In turn, organic Cu given in 75 % of daily
demand did not influence the intestinal morphology in adult rats. Dietary organic
Cu given to rats covering the daily demand in 50 or 75 % appears to be less
harmful with regard to the intestinal epithelium than when administered in 100 %
of daily demand.
PMID- 26432449
TI - The Effects of High Dietary Doses of Chromium(III) Complex with Propionic Acid on
Nutritional and Selected Blood Indices in Healthy Female Rats.
AB - People taking dietary supplements are usually determined to lose weight,
supplement nutrition or reduce the risk of illness and negative effects of their
state of health. Chromium(III) supplementation influence body composition and
mass, glucose and lipid metabolism and it enhance insulin action. This fact could
be of general interest because diabetes mellitus is an increasing health problem
in many countries. The study describes the effects of high dietary doses of
chromium(III) complex with propionic acid [Cr3] (from 100 to 1000 mg Cr . kg(-1)
diet) on the organisms of healthy female rats, with special regard to overall
nutritional, carbohydrate, lipid and blood biochemical and morphological and
haematological indices. The study was carried out on 30 10-week-old female Wistar
rats, which were divided into five equal groups (six animals in each): the
control group and four groups of tested animals which had free access to the diet
supplemented with 100, 200, 500 and 1000 mg Cr . kg(-1) (equivalent of 10, 20, 50
and 100 mg Cr . kg body weight (b.w.) . day(-1)), given as
[Cr3O(O2CCH2CH3)6(H2O)3]?NO3, also known as Cr3, for 4 weeks. There were no
significant differences in body mass gains, feeding efficiency ratio, internal
organ masses or blood serum glucose concentrations, except for some changes in
the serum triglycerides concentration, which decreased in the rats that received
500 and 1000 mg Cr . kg(-1) diet, as opposed to the group treated with 200 mg Cr
. kg(-1) diet. The dietary supplementation of Cr3 for 4 weeks at doses of 100 to
1000 mg Cr . kg(-1) diet did not affect overall nutritional indices and most
blood biochemical, morphological and haematological indices.
PMID- 26432450
TI - The Selenylation Modification of Epimedium Polysaccharide and Isatis Root
Polysaccharide and the Immune-enhancing Activity Comparison of Their Modifiers.
AB - Epimedium polysaccharide (EPS) and isatis root polysaccharide (IRPS) were
extracted, purified, and selenizingly modified by nitric acid-sodium selenite
method to obtain nine selenizing EPSs (sEPSs), sEPS1-sEPS9 and nine selenizing
IRPSs (sIRPSs), sIRPS1-sIRPS9, respectively. Their effects on chicken peripheral
lymphocyte proliferation in vitro were compared by MTT assay. The results showed
that selenium polysaccharides at appropriate concentration could promote
lymphocyte proliferation more significantly than unmodified polysaccharides,
sEPS5 and sIRPS5 with stronger actions were picked out and injected into the
chickens vaccinated with Newcastle disease vaccine in vivo tests. The peripheral
lymphocyte proliferation and serum antibody titer were determined. The results
showed that sEPS5 and sIRPS5 could elevate serum antibody titer and promote
lymphocyte proliferation more significantly than unmodified polysaccharides,
sEPS5 possessed the strongest efficacy. These results indicate that selenylation
modification can significantly enhance the immune-enhancing activity of EPS and
IRPS, and sEPS5 can be as a new-type immunopotentiator of chickens.
PMID- 26432451
TI - Proteomic Analysis to Elucidate the Antibacterial Action of Silver Ions Against
Bovine Mastitis Pathogens.
AB - Silver ions act as a powerful, broad-spectrum antimicrobial agent and are known
to kill over 650 different kinds of pathogens. We investigated the protein
expression pattern and identity after silver ion treatment in Escherichia coli
and Staphylococcus aureus, which are primarily responsible for the majority of
bovine mastitis cases using proteomics. Two-dimensional electrophoresis showed
that silver ion treatment significantly reduced 5 spot's density in E. coli and
S. aureus, respectively. We identified 10 proteins (alkyl hydroperoxide reductase
C22 subunit, phosphoglucomutase, fructose-1-phosphate kinase, putative carbamoyl
transferase, alpha-galactosidase, carbamate kinase, ornithine transcarbamoylase,
fumarate hydratase class II, alcohol dehydrogenase, and conserved hypothetical
protein) by matrix-assisted laser desorption ionization time of flight (MALDI
TOF). These results demonstrated that silver ions have bactericidal effects
through energy deprivation, inhibition of DNA replication, and accumulation of
oxidants in bovine mastitis pathogens and suggested that silver ions can be
applied for the treatment of bovine mastitis.
PMID- 26432452
TI - T-lymphocyte populations following a period of high volume training in female
soccer players.
AB - PURPOSE: To investigate the T-lymphocyte response to a period of increased
training volume in trained females compared to habitual activity in female
controls. METHODS: Thirteen trained female (19.8 +/- 1.9 yrs) soccer players were
monitored during a two-week long high volume training period (increased by 39%)
and thirteen female untrained (20.5 +/- 2.2 yrs) controls were monitored during
two-weeks of habitual activity. Blood lymphocytes, collected at rest, were
isolated before and after the two-week period. Isolated lymphocytes were assessed
for the cell surface expression of the co-receptor CD28, a marker of T-lymphocyte
naivety, and CD57 a marker used to identify highly-differentiated T-lymphocytes.
Co-expression of these markers was identified on helper CD4(+) and cytotoxic
CD8(+) T-lymphocytes. In addition a further population of gammadelta(+) T
lymphocytes were identified. Plasma was used to determine Cytomegalovirus (CMV)
serostatus. RESULTS: No difference was observed in the T-lymphocyte populations
following the two-week period of increased volume training. At baseline the
number of total CD3(+), cytotoxic CD8(+), naive (CD8(+) CD28(+) CD57(-)),
intermediate (CD8(+) CD28(+) CD57(+)) T-lymphocytes and the number and proportion
of gammadelta(+) T-lymphocytes were greater in the trained compared to the
untrained females (p<0.05). The proportion of CD4(+)T-lymphocytes was greater in
the untrained compared to the trained (p<0.05), in turn the CD4(+):CD8(+) ratio
was also greater in the untrained females (p<0.05). Inclusion of percentage body
fat as a covariate removed the main effect of training status in all T-lymphocyte
sub-populations, with the exception of the gammadelta(+) T-lymphocyte population.
8% of the untrained group was defined as positive for CMV whereas 23% of the
trained group was positive for CMV. However, CMV was not a significant covariate
in the analysis of T-lymphocyte proportions. CONCLUSION: The period of high
volume training had no effect on T-lymphocyte populations in trained females.
However, baseline training status differences were evident between groups. This
indicates that long-term exercise training, as opposed to short-term changes in
exercise volume, appears to elicit discernible changes in the composition of the
blood T-lymphocyte pool.
PMID- 26432453
TI - The capacity for volitional control of pharyngeal swallowing in healthy adults.
AB - INTRODUCTION: Previous research has documented that pressure and duration of
brainstem-generated pharyngeal swallowing can be cortically modulated. But there
is a commonly held belief that the sequence of pharyngeal pressure remains
constant. However, Huckabee et al. [19] reported a patient cohort who
demonstrated reduced latency of peak pressure in the proximal and distal pharynx,
disproportionate and sometimes inversely correlated with overall swallowing
duration, suggesting independent timing of underlying muscle contraction within
the overall pharyngeal response. This study examined if healthy adults can
volitionally produce altered latency of pharyngeal closure in isolation following
intensive training, thereby evaluating the capacity for pharyngeal adaptation in
a healthy system. METHOD: Six healthy participants were seen for intensive
training, consisting of daily one-hour sessions over two weeks (10 days) using
pharyngeal manometry as a visual biofeedback modality. The participants were
instructed to produce simultaneous pressure in the pharyngeal sensors when
swallowing. The temporal separation of peak proximal and distal pharyngeal
pressure was measured with discrete-sensor pharyngeal manometry at baseline,
during training with biofeedback, and following training without biofeedback.
RESULTS: Following intensive training, participants were able to reduce temporal
separation of peak pressure between the proximal and distal pharyngeal sensors
from a baseline median of 188 ms (IQR=231 ms) to 68 ms (IQR=92 ms; p=0.002). In
contrast, there was no significant change in overall swallowing duration during
training (p=0.41). However, change in pharyngeal pressure latency was moderately
correlated with both change in swallowing duration (r=0.444) and amplitude
(r=0.571) during training, and there was a reduction in swallowing duration post
training (p=0.03). CONCLUSION: Given intensive manometric biofeedback training,
participants substantially reduced temporal separation of peak proximal and
distal pharyngeal pressure when volitionally swallowing. However, correlation
with overall pressure and duration measures suggest the adaptation was one of
modulating the cumulative pharyngeal response rather than altering discrete
components of timing of pharyngeal pressure in isolation. This is inconsistent
with the pattern of behaviour documented by Huckabee et al. [19] in the patient
population. Further research on modulatory control over targeted aspects of the
pharyngeal swallow is needed, and may provide avenues for rehabilitative
treatment of patients with dysphagia.
PMID- 26432454
TI - Indiscernible Benefit of Double-Unit Umbilical Cord Blood Transplantation in
Children: A Single-Center Experience From Hong Kong.
AB - Double-unit umbilical cord blood (DU-UCB) may extend the use of UCB
transplantation and improve clinical outcomes. Data in the literature show that
single-unit dominance happened in a vast majority of recipients, and the
mechanism is unknown. We examined the clinical relevance and engraftment kinetics
of DU-UCB transplant in 65 consecutive children who underwent unrelated single
unit (n = 25) and double-unit (n = 40) UCB transplantation for various
hematological malignancies (n = 45) and nonmalignant disorders (n = 20). Our
result showed no discernible benefit to children receiving double-unit transplant
over those receiving single-unit transplant when the total nucleated cell (TNC)
doses are >=2.5 * 10(7)/kg, in terms of the hastening of the engraftment of
neutrophils and platelets, reduction of nonengraftment, disease recurrence, early
mortality, and graft-versus-host disease, despite significantly higher numbers of
TNCs in double units. Further analyses demonstrated that the phenomena were not
associated with underlying disease, duration of UCB storage, postthaw viability,
HLA disparity, ABO incompatibility, gender, or doses of TNCs, CD34(+) cells,
CD3(+) cells, or colony-forming units. Engrafting units in DU-UCB transplants
were notably associated with higher CD34(+) cell dose. Chimerism studies
demonstrated that single-unit dominance started before neutrophil engraftment in
DU-UCB transplants. Data from the study suggested no advantage of infusing double
unit UCB, if an adequately dosed single-unit UCB is available. Successful
prediction of the dominant graft would optimize algorithms of UCB selection and
maximize the long-term engraftment of chosen units.
PMID- 26432456
TI - Erratum to: Use of porous high-density polyethylene grafts in open rhinoplasty:
no infectious complication seen in spreader and dorsal grafts.
PMID- 26432455
TI - Molecular phylogeny of four homeobox genes from the purple sea star Pisaster
ochraceus.
AB - Homeobox genes cloned from the purple sea star Pisaster ochraceus (Phylum
Echinodermata/Class Asteroidea) were used along with related sequences available
from members of other representative animal phyla to generate molecular
phylogenies for Distal-less/Dlx, Hox5, Hox7, and Hox9/10 homeobox genes.
Phylogenetic relationships were inferred based on the predicted 60 amino acid
homeodomain, using amino acid (AA) and nucleotide (NT) models as well as the
recently developed codon substitution models of sequence evolution. The resulting
phylogenetic trees were mostly congruent with the consensus species-tree,
grouping these newly identified genes with those isolated from other Asteroidea.
This analysis also allowed a preliminary comparison of the performance of codon
models with that of NT and AA evolutionary models in the inference of homeobox
phylogeny. We found that, overall, the NT models displayed low reliability in
recovering major clades at the Superphylum/Phylum level, and that codon models
were slightly more dependable than AA models. Remarkably, in the majority of
cases, codon substitution models seemed to outperform both AA and NT models at
both the Class level and homeobox paralogy-group level of classification.
PMID- 26432457
TI - The effects of cryopreservation on angiogenesis modulation activity of human
amniotic membrane.
AB - Amniotic membrane (AM), as the innermost layer of placenta, has side dependent
effects on the angiogenesis. Cryopreservation is a necessary process to avoid the
challenging problems of fresh tissues; a procedure which makes the AM ready-to
use. Since the cryopreservation can influence the AM characteristics for
experimental and clinical purposes, in this study the effects of cryopreservation
were evaluated on angiogenesis modulation activity of the AM compared to fresh
tissues in an animal model. The AM was implanted mesenchymal side up or
epithelial side up in a rat dorsal skinfold chamber. The length and number of
branches of formed capillaries were measured via intravital microscopy after 7
days. The amount of IL-8 (interleukin-8) and TIMP-2 (Tissue Inhibitor of Matrix
Metalloproteinase-2) as two factors in amniotic cells which have great impacts on
angiogenesis were evaluated using ELISA assay. The epithelial surface of
cryopreserved AM had inhibitory effects on vessel formation. The cryopreserved
amniotic mesenchymal side increased the vessel length and sprout. The result of
cryopreserved AM on angiogenesis was similar to that of fresh tissues. The levels
of IL-8 and TIMP-2 in cryopreserved samples were significantly less than fresh
AMs which shows that angio-modulatory properties are not limited to the effects
of amnion epithelial and mesenchymal stem cells and the other components such as
extracellular matrix may contribute in angio-modulatory effects. These promising
results show that inducing and inhibitory effects of the AM, which make it an
appropriate candidate for different clinical situations, were maintained after
cryopreservation.
PMID- 26432458
TI - Role of Oxidative Stress in Modulating Unfolded Protein Response Activity in
Chronic Myeloid Leukemia Cell Line.
AB - Recently, it has been revealed that tyrosine kinase inhibitors (TKIs) act through
inducing both oxidative and endoplasmic reticulum (ER) stress in chronic myeloid
leukemia cells. However, ER stress signaling triggers both apoptotic and survival
processes within cells. Nevertheless, mechanisms by which TKIs avoid the pro
survival effects are not clear. The aim of this study was to evaluate the
potential role of oxidative stress in activity of unfolded protein response (UPR)
survival pathway within K562 cell line. METHODS: The expression of UPR survival
target genes, Xbp1, and Grp94 (glucose requiring protein 94) was studied in
single and combined exposure to oxidative and ER stress in K562 cell line by
quantitative and qualitative PCR. RESULTS: The expression of UPR-related survival
gene Grp94 was hampered by exposing to oxidative stress in cell induced with ER
stress. CONCLUSION: Interaction of oxidative and ER stress may role as a mediator
influencing UPR signaling activity.
PMID- 26432459
TI - Process limitations of a whole-cell P450 catalyzed reaction using a CYP153A-CPR
fusion construct expressed in Escherichia coli.
AB - Cytochrome P450s are interesting biocatalysts due to their ability to hydroxylate
non-activated hydrocarbons in a selective manner. However, to date only a few
P450-catalyzed processes have been implemented in industry due to the difficulty
of developing economically feasible processes. In this study, we have used the
CYP153A heme domain from Marinobacter aquaeolei fused to the reductase domain of
CYP102A1 from Bacillus megaterium (BM3) expressed in Escherichia coli. This self
sufficient protein chimera CYP153A-CPRBM3 G307A mutant is able to selectively
hydroxylate medium and long chain length fatty acids at the terminal position.
omega-Hydroxylated fatty acids can be used in the field of high-end polymers and
in the cosmetic and fragrance industry. Here, we have identified the limitations
for implementation of a whole-cell P450-catalyzed reaction by characterizing the
chosen biocatalyst as well as the reaction system. Despite a well-studied whole
cell P450 catalyst, low activity and poor stability of the artificial fusion
construct are the main identified limitations to reach sufficient biocatalyst
yield (mass of product/mass of biocatalyst) and space-time yield (volumetric
productivity) essential for an economically feasible process. Substrate and
product inhibition are also challenges that need to be addressed, and the
application of solid substrate is shown to be a promising option to improve the
process.
PMID- 26432461
TI - Transosseous Route for CT Fluoroscopy-Guided Radiofrequency Ablation of Lung
Tumors.
AB - PURPOSE: To retrospectively evaluate radiofrequency (RF) ablation of lung tumors
performed via the transosseous approach. MATERIALS AND METHODS: Twelve lung
tumors (mean diameter, 1.0 cm; range, 0.4-1.6 cm) in 12 patients were treated by
RF ablation via a transscapular and/or transrib route with the use of a bone
biopsy needle under computed tomographic fluoroscopy guidance. Therapeutic
outcomes evaluated included feasibility, safety, and local efficacy.
Complications were assessed based on the National Cancer Institute Common
Terminology Criteria for Adverse Events, version 4.0. RESULTS: The transosseous
route was successfully employed in all patients, and the electrode was
successfully advanced into all tumors with this approach. The mean distance of
penetrated bone was 0.57 cm (range, 0.19-1.16 cm). Complications occurred in
eight RF ablation sessions, including six grade 1 events (two cases of
pneumothorax and one case each of asymptomatic rib fracture 6 mo after treatment,
neuralgia, pulmonary hemorrhage, and hemothorax), two grade 2 events (pneumonia
and high fever), and one grade 3 event (pneumothorax requiring pleurodesis). No
adverse events of grade >= 4 occurred. The mean and median tumor follow-up
periods were 19.5 and 15.2 mo (range, 3.0-41.5 mo). Local progression occurred in
two cases at 3 and 12 mo after treatment and was successfully treated with a
second RF ablation procedure. The technique efficacy rates were 91.7% at 6 mo,
81.5% at 1 y, and 81.5% at 2 y. CONCLUSIONS: The transosseous approach was
feasible in computed tomographic fluoroscopy-guided RF ablation of select lung
tumors when no other option was available.
PMID- 26432460
TI - Production of the polyketide 6-deoxyerythronolide B in the heterologous host
Bacillus subtilis.
AB - Polyketides, such as erythromycin, are complex natural products with diverse
therapeutic applications. They are synthesized by multi-modular megaenzymes, so
called polyketide synthases (PKSs). The macrolide core of erythromycin, 6
deoxyerythronolide B (6dEB), is produced by the deoxyerythronolide B synthase
(DEBS) that consists of three proteins each with a size of 330-370 kDa. We cloned
and investigated the expression of the corresponding gene cluster from
Saccharopolyspora erythraea, which comprises more than 30 kb, in Bacillus
subtilis. It is shown that the DEBS genes are functionally expressed in B.
subtilis when the native eryAI-III operon was separated into three individual
expression cassettes with optimized ribosomal binding sites. A synthesis of 6dEB
could be detected by using the acetoin-inducible acoA promoter and a fed-batch
simulating EnBase-cultivation strategy. B. subtilis was capable of the secretion
of 6dEB into the medium. In order to improve the 6dEB production, several genomic
modifications of this production strain were tested. This included the knockout
of the native secondary metabolite clusters of B. subtilis for the synthesis of
surfactin (26 kb), bacillaene (76 kb), and plipastatin (38 kb). It is revealed
that the deletion of the prpBD operon, responsible for propionyl-CoA utilization,
resulted in a significant increase of the 6dEB product yield when exogenous
propionate is provided. Although the presented B. subtilis 6dEB production strain
is not competitive with established Escherichia coli 6dEB production strains, the
results of this study indicate that B. subtilis is a suitable heterologous host
for the secretory production of a complex polyketide.
PMID- 26432462
TI - Novel sporadic and recurrent mutations in KRT5 and KRT14 genes in Polish
epidermolysis bullosa simplex patients: further insights into epidemiology and
genotype-phenotype correlation.
AB - Epidermolysis bullosa simplex (EBS) is a hereditary genodermatosis characterised
by trauma-induced intraepidermal blistering of the skin. EBS is mostly caused by
mutations in the KRT5 and KRT14 genes. Disease severity partially depends on the
affected keratin type and may be modulated by mutation type and location. The aim
of our study was to identify the molecular defects in KRT5 and KRT14 in a cohort
of 46 Polish and one Belarusian probands with clinical suspicion of EBS and to
determine the genotype-phenotype correlation. The group of 47 patients with
clinical recognition of EBS was enrolled in the study. We analysed all coding
exons of KRT5 and KRT14 using Sanger sequencing. The pathogenic status of novel
variants was evaluated using bioinformatical tools, control group analysis (DNA
from 100 healthy population-matched subjects) and probands' parents testing. We
identified mutations in 80 % of patients and found 29 different mutations, 11 of
which were novel and six were found in more than one family. All novel mutations
were ascertained as pathogenic. In the majority of cases, the most severe
genotype was associated with mutations in highly conserved regions. In some
cases, different inheritance mode and clinical significance, than previously
reported by others, was observed. We report 11 novel variants and show novel
genotype-phenotype correlations. Our data give further insight into the natural
history of EBS molecular pathology, epidemiology and mutation origin.
PMID- 26432463
TI - Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in
patients with lupus and antiphospholipid antibodies: results of the PROMISSE
study.
AB - BACKGROUND: Over 20% of pregnancies in patients with systemic lupus erythematosus
(SLE) and/or antiphospholipid antibodies (APL) result in an adverse pregnancy
outcome (APO) related to abnormal placentation. The ability to identify, early in
pregnancy, patients who are destined for poor outcomes would significantly impact
care of this high-risk population. In nonautoimmune patients, circulating
angiogenic factors are dysregulated in disorders of placentation, such as
preeclampsia (PE) and fetal growth restriction. OBJECTIVE: We sought to determine
whether early dysregulation of circulating angiogenic factors can predict APO in
high-risk SLE and/or APL pregnancies. STUDY DESIGN: We used data and samples from
the Predictors of Pregnancy Outcome: Biomarkers in APL Syndrome and SLE
(PROMISSE), a multicenter prospective study that enrolled 492 pregnant women with
SLE and/or APL from September 2003 through August 2013. Patients were followed
through pregnancy from <12 weeks gestation. Circulating levels of soluble fms
like tyrosine kinase-1 (sFlt1), placental growth factor (PlGF), and soluble
endoglin were measured monthly and subjects followed up for APO, classified as
severe (PE <34 weeks, fetal/neonatal death, indicated preterm delivery <30 weeks)
or moderate (PE >=34 weeks, indicated preterm delivery 30-36 weeks, growth
restriction without PE). RESULTS: Severe APOs occurred in 12% and moderate APOs
in 10% of patients. By 12-15 weeks, sFlt1, PlGF, and soluble endoglin levels were
markedly altered in women who developed severe APO. After adjusting for clinical
risk factors, sFlt1 was the strongest predictor of severe APO among 12-15 week
measures (odds ratio, 17.3 comparing highest and lowest quartiles; 95% confidence
interval [CI], 3.5-84.8; positive predictive value [PPV], 61%; negative
predictive value [NPV], 93%). At 16-19 weeks, the combination of sFlt1 and PlGF
was most predictive of severe APO, with risk greatest for subjects with both PlGF
in lowest quartile (<70.3 pg/mL) and sFlt1 in highest quartile (>1872 pg/mL; odds
ratio, 31.1; 95% CI, 8.0-121.9; PPV, 58%; NPV, 95%). Severe APO rate in this high
risk subgroup was 94% (95% CI, 70-99.8%), if lupus anticoagulant or history of
high blood pressure was additionally present. In contrast, among patients with
both sFlt1 <1872 pg/mL and PlGF >70.3 pg/mL, rate of severe APO was only 4.6%
(95% CI, 2.1-8.6%). CONCLUSION: Circulating angiogenic factors measured during
early gestation have a high NPV in ruling out the development of severe adverse
outcomes among patients with SLE and/or APL syndrome. Timely risk stratification
of patients is important for effective clinical care and optimal allocation of
health care resources.
PMID- 26432465
TI - Fetal tissue research: an ongoing story of professionally responsible success.
AB - Therapies derived from fetal tissue research are some of the greatest success
stories in medicine. Research using fetal tissue has allowed for development of
vaccines for numerous diseases including polio, rubella, and measles. These
vaccines have saved countless lives, improved quality of life, and decreased the
need for induced abortion secondary to congenital infection. Research using cell
lines derived from fetal tissue has assisted in better understanding disease
pathogenesis and has served to produce human proteins as research reagents and
therapies. Ongoing research points to the potential for fetal tissue to be used
to cure debilitating diseases such as Parkinson disease. These scientific and
medical advances are dependent on the use of fetal tissue from aborted fetuses.
While the practice of induced abortion despite societal benefit may be
theologically objectionable to some, these practices are professionally
responsible. Federal regulations exist to discourage patients from being
influenced by the societal benefit of fetal research in arriving at the decision
to terminate as well as to prevent researchers from influencing a patient's
decision. After a patient has chosen termination of pregnancy, it is consistent
with professional responsibility to allow her to choose the disposition of the
cadaveric fetal tissue. While some may view induced abortion and societal benefit
from this practice as an ethical burden, the principle of justice makes it
ethically obligatory to bear this ethical burden. The success story of cadaveric
fetal tissue research and treatment should continue unhindered, to fulfill
professional responsibility to current and future patients.
PMID- 26432464
TI - Celiac disease and obstetric complications: a systematic review and metaanalysis.
AB - The aim of this metaanalysis was to evaluate the risk of the development of
obstetric complications in women with celiac disease. We searched electronic
databases from their inception until February 2015. We included all cohort
studies that reported the incidence of obstetric complications in women with
celiac disease compared with women without celiac disease (ie, control group).
Studies without a control group and case-control studies were excluded. The
primary outcome was defined a priori and was the incidence of a composite of
obstetric complications that included intrauterine growth restriction, small for
gestational age, low birthweight, preeclampsia and preterm birth. Secondary
outcomes included the incidence of preterm birth, intrauterine growth
restriction, stillbirth, preeclampsia, small for gestational age, and low
birthweight. The review was registered with PROSPERO (CRD42015017263) before data
extraction. All authors were contacted to obtain the original databases and
perform individual participant data metaanalysis. Primary and secondary outcomes
were assessed in the aggregate data analysis and in the individual participant
data metaanalysis. We included 10 cohort studies (4,844,555 women) in this
metaanalysis. Four authors provided the entire databases for the individual
participant data analysis. Because none of the included studies stratified data
for the primary outcome (ie, composite outcome), the assessment of this outcome
for the aggregate analysis was not feasible. Aggregate data analysis showed that,
compared with women in the control group, women with celiac disease (both treated
and untreated) had a significantly higher risk of the development of preterm
birth (adjusted odds ratio, 1.35; 95% confidence interval, 1.09-1.66),
intrauterine growth restriction (odds ratio, 2.48; 95% confidence interval, 1.32
4.67), stillbirth (odds ratio, 4.84; 95% confidence interval, 1.08-21.75), low
birthweight (odds ratio, 1.63; 95% confidence interval, 1.06-2.51), and small for
gestational age (odds ratio, 4.52; 95% confidence interval, 1.02-20.08); no
statistically significant difference was found in the incidence of preeclampsia
(odds ratio, 2.45; 95% confidence interval, 0.90-6.70). The risk of preterm birth
was still significantly higher both in the subgroup analysis of only women with
diagnosed and treated celiac disease (odds ratio, 1.26; 95% confidence interval,
1.06-1.48) and in the subgroup analysis of only women with undiagnosed and
untreated celiac disease (odds ratio, 2.50; 95% confidence interval; 1.06-5.87).
Women with diagnosed and treated celiac disease had a significantly lower risk of
the development of preterm birth, compared with undiagnosed and untreated celiac
disease (odds ratio, 0.80; 95% confidence interval, 0.64-0.99). The individual
participant data metaanalysis showed that women with celiac disease had a
significantly higher risk of composite obstetric complications compared with
control subjects (odds ratio, 1.51; 95% confidence interval, 1.17-1.94). Our
individual participant data concurs with the aggregate analysis for all the
secondary outcomes. In summary, women with celiac disease had a significantly
higher risk of the development of obstetric complications that included preterm
birth, intrauterine growth restriction, stillbirth, low birthweight, and small
for gestational age. Since the treatment with gluten-free diet leads to a
significant decrease of preterm delivery, physicians should warn these women
about the importance of a strict diet to improve obstetric outcomes. Future
studies calculating cost-effectiveness of screening for celiac disease during
pregnancy, which could be easily performed, economically and noninvasively, are
needed. In addition, further studies are required to determine whether women with
adverse pregnancy outcomes should be screened for celiac disease, particularly in
countries where the prevalence is high.
PMID- 26432467
TI - Perinatal risks of planned home births in the United States.
PMID- 26432468
TI - Association between guideline recommended drugs and death in older adults with
multiple chronic conditions: population based cohort study.
AB - OBJECTIVE: To estimate the association between guideline recommended drugs and
death in older adults with multiple chronic conditions. DESIGN: Population based
cohort study. SETTING: Medicare Current Beneficiary Survey cohort, a nationally
representative sample of Americans aged 65 years or more. PARTICIPANTS: 8578
older adults with two or more study chronic conditions (atrial fibrillation,
coronary artery disease, chronic kidney disease, depression, diabetes, heart
failure, hyperlipidemia, hypertension, and thromboembolic disease), followed
through 2011. EXPOSURES: Drugs included beta blockers, calcium channel blockers,
clopidogrel, metformin, renin-angiotensin system (RAS) blockers; selective
serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake
inhibitors (SNRIs); statins; thiazides; and warfarin. MAIN OUTCOME MEASURE:
Adjusted hazard ratios for death among participants with a condition and taking a
guideline recommended drug relative to participants with the condition not taking
the drug and among participants with the most common combinations of four
conditions. RESULTS: Over 50% of participants with each condition received the
recommended drugs regardless of coexisting conditions; 1287/8578 (15%)
participants died during the three years of follow-up. Among cardiovascular
drugs, beta blockers, calcium channel blockers, RAS blockers, and statins were
associated with reduced mortality for indicated conditions. For example, the
adjusted hazard ratio for beta blockers was 0.59 (95% confidence interval 0.48 to
0.72) for people with atrial fibrillation and 0.68 (0.57 to 0.81) for those with
heart failure. The adjusted hazard ratios for cardiovascular drugs were similar
to those with common combinations of four coexisting conditions, with trends
toward variable effects for beta blockers. None of clopidogrel, metformin, or
SSRIs/SNRIs was associated with reduced mortality. Warfarin was associated with a
reduced risk of death among those with atrial fibrillation (adjusted hazard ratio
0.69, 95% confidence interval 0.56 to 0.85) and thromboembolic disease (0.44,
0.30 to 0.62). Attenuation in the association with reduced risk of death was
found with warfarin in participants with some combinations of coexisting
conditions. CONCLUSIONS: Average effects on survival, particularly for
cardiovascular study drugs, were comparable to those reported in randomized
controlled trials but varied for some drugs according to coexisting conditions.
Determining treatment effects in combinations of conditions may guide prescribing
in people with multiple chronic conditions.
PMID- 26432466
TI - New development of the yolk sac theory in diabetic embryopathy: molecular
mechanism and link to structural birth defects.
AB - Maternal diabetes mellitus is a significant risk factor for structural birth
defects, including congenital heart defects and neural tube defects. With the
rising prevalence of type 2 diabetes mellitus and obesity in women of
childbearing age, diabetes mellitus-induced birth defects have become an
increasingly significant public health problem. Maternal diabetes mellitus in
vivo and high glucose in vitro induce yolk sac injuries by damaging the
morphologic condition of cells and altering the dynamics of organelles. The yolk
sac vascular system is the first system to develop during embryogenesis;
therefore, it is the most sensitive to hyperglycemia. The consequences of yolk
sac injuries include impairment of nutrient transportation because of
vasculopathy. Although the functional relationship between yolk sac vasculopathy
and structural birth defects has not yet been established, a recent study reveals
that the quality of yolk sac vasculature is related inversely to embryonic
malformation rates. Studies in animal models have uncovered key molecular
intermediates of diabetic yolk sac vasculopathy, which include hypoxia-inducible
factor-1alpha, apoptosis signal-regulating kinase 1, and its inhibitor
thioredoxin-1, c-Jun-N-terminal kinases, nitric oxide, and nitric oxide synthase.
Yolk sac vasculopathy is also associated with abnormalities in arachidonic acid
and myo-inositol. Dietary supplementation with fatty acids that restore lipid
levels in the yolk sac lead to a reduction in diabetes mellitus-induced
malformations. Although the role of the human yolk in embryogenesis is less
extensive than in rodents, nevertheless, human embryonic vasculogenesis is
affected negatively by maternal diabetes mellitus. Mechanistic studies have
identified potential therapeutic targets for future intervention against yolk sac
vasculopathy, birth defects, and other complications associated with diabetic
pregnancies.
PMID- 26432469
TI - A-kinase anchoring protein 2 is required for calcitonin-mediated invasion of
cancer cells.
AB - Expression of neuropeptide calcitonin (CT) and its receptor (CTR) is frequently
elevated in prostate cancers (PCs) and activation of CT-CTR axis in non-invasive
PC cells induces an invasive phenotype. Specific, cell-permeable inhibitors of
protein kinase A abolish CTR-stimulated invasion of PC cells. Since PKA is
ubiquitously distributed in cells, the present study examined the mechanism(s) by
which CTR-stimulated PKA activity is regulated in time and space. CT reduced cell
adhesion but increased invasion of PC cells. Both these actions were abolished by
st-Ht31 inhibitory peptide suggesting the involvement of an A-kinase anchoring
protein (AKAP) in CT action. Next, we identified the AKAP associated with CT
action by the subtraction of potential AKAP candidates using siRNAs. Knock-down
of membrane-associated AKAP2, but not other AKAPs, abolished CT-stimulated
invasion. Stable knock-down of AKAP2 in PC3-CTR cells remarkably decreased their
cell proliferation, invasion, clonogenicity and ability to form orthotopic tumors
and distant metastases in nude mice. Re-expression of AKAP2-wt restored these
characteristics. Primary PC specimens displayed remarkable upregulation of
CTR/AKAP2 expression as compared to benign prostates. Metastatic cancers
displayed significantly higher CTR/AKAP2 expression than localized cancers. These
results for the first time demonstrate that AKAP2 is expressed in human
prostates, its expression is elevated in metastatic prostate cancer, and the
knock-down of its expression remarkably decreased tumorigenicity and metastatic
ability of prostate cancer cells. AKAP2 may serve as a critical component of CTR
mediated oncogenic actions.
PMID- 26432470
TI - Targeting muscle signaling pathways to minimize adverse effects of androgen
deprivation.
AB - Androgen deprivation therapy (ADT) is a highly effective treatment used in ~30%
of men with prostate cancer. Adverse effects of ADT on muscle are significant
with consistent losses in muscle mass. However, effects of ADT on muscle strength
and physical function, of most relevance to the patient, are less well
understood. This is in part due to the fact that muscle effects of ADT at the
cellular, genetic and protein level, critical to the understanding of the
pathophysiology of sarcopenia, have come into focus only recently. This review
highlights the complexity of androgen-dependent signaling in muscle with an
emphasis on recent findings in the regulation of muscle growth and muscle atrophy
pathways. Furthermore, the effects of ADT and testosterone on skeletal muscle
histology, gene expression and protein transcription are discussed. A better
mechanistic understanding of the regulation of muscle mass and function by
androgens should not only pave the way for developing targeted promyogenic
interventions for men with prostate cancer receiving ADT but also may have wider
implications for age-associated sarcopenia in the general population.
PMID- 26432471
TI - BML-111 attenuates acute lung injury in endotoxemic mice.
AB - BACKGROUND: BML-111 is a lipoxin receptor agonist that has protective effects in
various lung injury models. We tried to elucidate whether BML-111 could mitigate
lung injury in a mouse model of endotoxemia and endothelial hyperpermeability in
vitro. METHODS: The effect of BML-111 on lung injury was evaluated using C57BL/6
mice and human umbilical vein endothelial cells (HUVECs). Male C57BL/6 mice were
intraperitoneally injected with normal saline, BML-111, and/or the lipoxin
receptor antagonist Boc-2. Then, either lipopolysaccharide (LPS) or normal saline
was given intraperitoneally. Lung injury was assessed by a pathohistologic
examination for neutrophil infiltration, pulmonary endothelial permeability, and
inflammatory cytokines in lung tissue and bronchoalveolar lavage fluid. HUVECs
were treated with or without BML-111 before incubation with LPS for 24 h. Boc-2
was also tested as a novel inhibitor of BML-111. A Transwell assay was used to
evaluate the permeability of HUVECs. Junction protein expression was also
assessed. RESULTS: BML-111 significantly improved the mouse survival rate,
reduced body weight loss, attenuated the pulmonary pathologic changes, inhibited
neutrophil infiltration and proinflammatory cytokine production, and mitigated
endothelial hyperpermeability. The decreased expression of junction proteins
induced by LPS in lung tissue and endothelial cells were upregulated by BML-111.
In addition, BML-111 inhibited the activation of the Akt, ERK1/2, and p38 MAPK
signaling pathways. However, the beneficial effects of BML-111 were abolished by
Boc-2. CONCLUSIONS: BML-111 attenuated lung injury in endotoxemic mice and
mitigated endothelial hyperpermeability by upregulating the expression of
junction proteins.
PMID- 26432472
TI - Evaluation of QSAR models for predicting the partition coefficient (log P) of
chemicals under the REACH regulation.
AB - The partition coefficient (log P) is a physicochemical parameter widely used in
environmental and health sciences and is important in REACH and CLP regulations.
In this regulatory context, the number of existing experimental data on log P is
negligible compared to the number of chemicals for which it is necessary. There
are many models to predict log P and we have selected a number of free programs
to examine how they predict the log P of chemicals registered for REACH and to
evaluate wheter they can be used in place of experimental data. Some results are
good, especially if the information on the applicability domain of the models is
considered, with R(2) values from 0.7 to 0.8 and root mean square error (RMSE)
from 0.8 to 1.5.
PMID- 26432473
TI - Examining confounding by diet in the association between perfluoroalkyl acids and
serum cholesterol in pregnancy.
AB - BACKGROUND: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA)
have consistently been associated with higher cholesterol levels in cross
sectional studies. Concerns have, however, been raised about potential
confounding by diet and clinical relevance. OBJECTIVE: To examine the association
between concentrations of PFOS and PFOA and total cholesterol in serum during
pregnancy taking into considerations confounding by diet. METHODS: 854 Danish
women who gave birth in 1988-89 and provided a blood sample and reported their
diet in week 30 of gestation. RESULTS: Mean serum PFOS, PFOA and total
cholesterol concentrations were 22.3 ng/mL, 4.1 ng/mL and 7.3 mmol/L,
respectively. Maternal diet was a significant predictor of serum PFOS and PFOA
concentrations. In particular intake of meat and meat products was positively
associated while intake of vegetables was inversely associated (P for trend
<0.01) with relative difference between the highest and lowest quartile in PFOS
and PFOA concentrations ranging between 6% and 25% of mean values. After
adjustment for dietary factors both PFOA and PFOS were positively and similarly
associated with serum cholesterol (P for trend <=0.01). For example, the mean
increase in serum cholesterol was 0.39 mmol/L (95%CI: 0.09, 0.68) when comparing
women in the highest to lowest quintile of PFOA concentrations. In comparison the
mean increase in serum cholesterol was 0.61 mmol/L (95%CI: 0.17, 1.05) when
comparing women in the highest to lowest quintile of saturated fat intake.
CONCLUSION: In this study associations between PFOS and PFOA with serum
cholesterol appeared unrelated to dietary intake and were similar in magnitude as
the associations between saturated fat intake and serum cholesterol.
PMID- 26432474
TI - Reply.
PMID- 26432475
TI - Reply.
PMID- 26432476
TI - Subcutaneous Ustekinumab Provides Clinical Benefit for Two-Thirds of Patients
With Crohn's Disease Refractory to Anti-Tumor Necrosis Factor Agents.
AB - BACKGROUND & AIMS: Ustekinumab, a human monoclonal antibody against the p40
subunit of interleukins-12 and -23, is effective in inducing and maintaining
remission in patients with luminal Crohn's disease (CD). We assessed the efficacy
and safety of subcutaneous ustekinumab in patients with anti-tumor necrosis
factor (anti-TNF) refractory CD. METHODS: We performed a retrospective
observational study, collecting data from the Groupe d'Etude Therapeutique des
Affections Inflammatoires du tube Digestif on 122 consecutive patients with
active CD refractory to anti-TNF therapy who received at least 1 subcutaneous
injection of ustekinumab from March 2011 to December 2014, in 20 tertiary centers
in Europe. Subjects were followed for at least 3 months. The primary outcome was
clinical benefit, defined as reductions in symptoms and biochemical markers of CD
and complete weaning from steroids, without surgery or immunosuppressant
therapies. RESULTS: Seventy-nine patients (65%) had a clinical benefit within 3
months of receiving ustekinumab. Concomitant immunosuppressant therapy at study
inclusion increased the odds for a clinical benefit from ustekinumab (odds ratio,
5.43; 95% confidence interval, 1.14-25.77; P = .03). Over a median follow-up
period of 9.8 months (interquartile range, 5.3-14.5 months), the cumulative
probabilities that patients maintained the clinical benefit for 6 and 12 months
after introduction of ustekinumab were 93% and 68%, respectively. CONCLUSIONS:
Almost two-thirds of patients with CD refractory to at least 1 anti-TNF agent
receive clinical benefit from ustekinumab therapy, not requiring steroids for up
to 12 months afterward. While awaiting results from ongoing trials, ustekinumab
can be considered for use in these patients.
PMID- 26432477
TI - Reply.
PMID- 26432478
TI - Reply.
PMID- 26432479
TI - Genetic manipulation of microglia during brain development and disease.
PMID- 26432480
TI - Bone marrow-derived macrophages and the CNS: An update on the use of experimental
chimeric mouse models and bone marrow transplantation in neurological disorders.
AB - The central nervous system (CNS) is a very unique system with multiple features
that differentiate it from systemic tissues. One of the most captivating aspects
of its distinctive nature is the presence of the blood brain barrier (BBB), which
seals it from the periphery. Therefore, to preserve tissue homeostasis, the CNS
has to rely heavily on resident cells such as microglia. These pivotal cells of
the mononuclear lineage have important and dichotomous roles according to various
neurological disorders. However, certain insults can overwhelm microglia as well
as compromising the integrity of the BBB, thus allowing the infiltration of bone
marrow-derived macrophages (BMDMs). The use of myeloablation and bone marrow
transplantation allowed the generation of chimeric mice to study resident
microglia and infiltrated BMDM separately. This breakthrough completely
revolutionized the way we captured these 2 types of mononuclear phagocytic cells.
We now realize that microglia and BMDM exhibit distinct features and appear to
perform different tasks. Since these cells are central in several pathologies, it
is crucial to use chimeric mice to analyze their functions and mechanisms to
possibly harness them for therapeutic purpose. This review will shed light on the
advent of this methodology and how it allowed deciphering the ontology of
microglia and its maintenance during adulthood. We will also compare the
different strategies used to perform myeloablation. Finally, we will discuss the
landmark studies that used chimeric mice to characterize the roles of microglia
and BMDM in several neurological disorders. This article is part of a Special
Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus
Schwaninger.
PMID- 26432481
TI - Oxidative stress and its impact on neurons and glia in multiple sclerosis
lesions.
PMID- 26432483
TI - Diabetes mellitus and Takotsubo syndrome in two Spanish cohorts.
PMID- 26432482
TI - Exosomes as new diagnostic tools in CNS diseases.
PMID- 26432484
TI - Comparative effect on platelet function of a fixed-dose aspirin and clopidogrel
combination versus separate formulations in patients with coronary artery
disease: A phase IV, multicenter, prospective, 4-week non-inferiority trial.
AB - BACKGROUND/OBJECTIVES: The effect of aspirin and clopidogrel in a fixed-dose
combination (FDC) on platelet function was compared with separate formulations in
patients that had undergone percutaneous coronary intervention (PCI) with drug
eluting stent (DES). METHODS: This was a phase IV, prospective, multicenter,
single-arm, non-inferiority study. Patients that had taken aspirin 100 mg and
clopidogrel 75 mg once daily as separate formulations for >6 months after PCI
with DES were enrolled, and then switched to an aspirin/clopidogrel FDC once
daily for 4 weeks. Platelet reactivity was determined using the VerifyNow(r)
P2Y12 assay at baseline (immediately prior to switching) and 4 weeks later.
RESULTS: A total of 648 patients (the full-analysis population; age, 63.6+/-9.0
years; male, 76.5%) finished the study, and 565 (the per-protocol population)
completed without protocol violations. In the per-protocol population, the %
inhibitions of P2Y12 and ARU were not significantly different between baseline
and after 4 weeks of FDC treatment (29.2+/-20.0% to 29.0+/-19.9%, P=0.708;
445.1+/-69.2 to 446.2+/-63.0, P=0.799, respectively) and the difference in P2Y12
inhibition observed did not exceed the predetermined limit of non-inferiority
(95% CI, -0.9 to 1.3). In the full-analysis population, the % inhibitions of
P2Y12, PRU, and ARU were not significantly changed after 4 weeks of FDC
treatment. CONCLUSIONS: This study demonstrates that the efficacy of platelet
inhibition by an aspirin/clopidogrel FDC was not inferior to that of separate
aspirin and clopidogrel formulations in patients that had undergone PCI with DES.
PMID- 26432485
TI - Giant aneurysmal evolution of a spontaneous coronary artery dissection in the
postpartum.
PMID- 26432486
TI - Remote monitoring of implantable devices: Should we continue to ignore it?
AB - The number of patients with implantable cardioverter defibrillators (ICDs) is
increasing. In addition to improve survival, ICD can collect data related to
device function and physiological parameters. Remote monitoring (RM) of these
data allows early detection of technical or clinical problems and a prompt
intervention (reprogramming device or therapy adjustment) before the patient
require hospitalization. RM is not a substitute for emergency service and its
consultation is now limited during working hours. Thus, a consent form is
required to inform patients about benefits and limitations. The available studies
indicate that remote monitoring is more effective than traditional calendar face
to face based encounters. RM is safe, highly reliable, cost efficient, allows
quick reply to failures, and reduces the number of scheduled visits and the
incidence of inappropriate shocks with a positive impact on survival. It follows
that RM has the credentials to be the standard of care for ICD management;
however, unfortunately, there is a delay in physician acceptance and
implementation. The recent observations from randomized IN-TIME study that showed
a clear survival benefit with RM in heart failure patients have encouraged us to
review both the negative and positive aspects of RM collected in a little more
than a decade.
PMID- 26432487
TI - Circulating microparticle signature in coronary and peripheral blood of ST
elevation myocardial infarction patients in relation to pain-to-PCI elapsed time.
AB - BACKGROUND: Circulating microparticle (cMP) levels are increased in the acute
phase of ST-elevation myocardial infarction (STEMI) and associate with
microvascular obstruction; however, the precise cMP-parental cell signature and
activation level are not elucidated. Here, we aimed to study the cMP signature in
STEMI-patients and whether cMP phenotype changes in relation to onset of pain-to
PCI [ischemic time (IT)]-elapsed time. METHODS: Blood was taken at PCI from the
culprit coronary and the peripheral circulation in STEMI-patients (N=40). Two
control groups were included: peripheral blood of age-matched patients recovering
from STEMI [after 72 h] and of control individuals (N=20/group). cMP-parental
origin and activation level were characterized by triple-labeling flow cytometry.
RESULTS: Procoagulant annexin V-positive cMPs bearing parental cell markers as
well as markers of activated cells displayed a significantly different profile in
STEMI-patients, in control individuals and in patients recovering from STEMI.
cMPs derived from monocytes, endothelium, and activated vascular cells were
higher in the culprit coronary artery than in peripheral blood in STEMI-patients,
especially in patients intervened at short IT. Indeed, cMP levels in coronary
blood were inversely related to IT duration (more abundant in thrombi with pain
to-PCI time<180 min). CONCLUSIONS: A characteristic [CD66b+/CD62E+/CD142+] cMP
signature in the systemic circulation reflects the formation of coronary
thrombotic occlusions in STEMI-patients. Changes in the cMP signature in the
culprit coronary artery blood reveal the sensitivity of MPs to detect the
ischemia-elapsed time. Interestingly, cMPs in peripheral blood may be sensitive
markers of the thrombo-occlusive vascular process developing in the coronary
arteries of STEMI-patients.
PMID- 26432488
TI - Renal artery anatomy affects the blood pressure response to renal denervation in
patients with resistant hypertension.
AB - BACKGROUND: Renal denervation (RDN) has been shown to reduce blood pressure (BP),
muscle sympathetic nerve activity (MSNA) and target organ damage in patients with
resistant hypertension (RH) and bilateral single renal arteries. The safety and
efficacy of RDN in patients with multiple renal arteries remains unclear.
METHODS: We measured office and 24-hour BP at baseline, 3 and 6 months following
RDN in 91 patients with RH, including 65 patients with single renal arteries
bilaterally (group 1), 16 patients with dual renal arteries on either one or both
sides (group 2) and 10 patients with other anatomical constellations or
structural abnormalities (group 3). Thirty nine out of 91 patients completed MSNA
at baseline and follow-up. RESULTS: RDN significantly reduced office and daytime
SBP in group 1 at both 3 and 6 months follow-up (P<0.001) but not in groups 2 and
3. Similarly, a significant reduction in resting baseline MSNA was only observed
in group 1 (P<0.05). There was no deterioration in kidney function in any group.
CONCLUSION: While RDN can be performed safely irrespective of the underlying
renal anatomy, the presence of single renal arteries with or without structural
abnormalities is associated with a more pronounced BP and MSNA lowering effect
than the presence of dual renal arteries in patients with RH. However, when
patients with dual renal arteries received renal nerve ablation in all arteries
there was trend towards a greater BP reduction. Insufficient renal sympathetic
nerve ablation may account for these differences.
PMID- 26432490
TI - Prognostic implications of pericardial effusion: The importance of underlying
etiology.
PMID- 26432491
TI - Electrocardiogram T-wave inversions in asymptomatic, "asymptomatic", and
symptomatic patients: A need for exploration for underlying Takotsubo syndrome.
PMID- 26432489
TI - Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca(2+) release
events in a rodent model of early stage diabetes: The arrhythmogenic substrate.
AB - BACKGROUND: Heart failure and arrhythmias occur more frequently in patients with
type 2 diabetes (T2DM) than in the general population. T2DM is preceded by a
prediabetic condition marked by elevated reactive oxygen species (ROS) and
subclinical cardiovascular defects. Although multifunctional Ca2+ calmodulin
dependent protein kinase II (CaMKII) is ROS-activated and CaMKII hyperactivity
promotes cardiac diseases, a link between prediabetes and CaMKII in the heart is
unprecedented. OBJECTIVES: To prove the hypothesis that increased ROS and CaMKII
activity contribute to heart failure and arrhythmogenic mechanisms in early stage
diabetes. METHODS-RESULTS: Echocardiography, electrocardiography, biochemical and
intracellular Ca2+ (Ca2+i) determinations were performed in fructose-rich diet
induced impaired glucose tolerance, a prediabetes model, in rodents. Fructose
rich diet rats showed decreased contractility and hypertrophy associated with
increased CaMKII activity, ROS production, oxidized CaMKII and enhanced CaMKII
dependent ryanodine receptor (RyR2) phosphorylation compared to rats fed with
control diet. Isolated cardiomyocytes from fructose-rich diet showed increased
spontaneous Ca2+i release events associated with spontaneous contractions, which
were prevented by KN-93, a CaMKII inhibitor, or addition of Tempol, a ROS
scavenger, to the diet. Moreover, fructose-rich diet myocytes showed increased
diastolic Ca2+ during the burst of spontaneous Ca2+i release events. Mice treated
with Tempol or with sarcoplasmic reticulum-targeted CaMKII-inhibition by
transgenic expression of the CaMKII inhibitory peptide AIP, were protected from
fructose-rich diet-induced spontaneous Ca2+i release events, spontaneous
contractions and arrhythmogenesis in vivo, despite ROS increases. CONCLUSIONS:
RyR2 phosphorylation by ROS-activated CaMKII, contributes to impaired glucose
tolerance-induced arrhythmogenic mechanisms, suggesting that CaMKII inhibition
could prevent prediabetic cardiovascular complications and/or evolution.
PMID- 26432492
TI - Can electrical shock provide ST-segment resolution in patients with ST-segment
elevation myocardial infarction?
PMID- 26432493
TI - Dipeptidyl peptidase-4 inhibitors and the ischemic heart: Additional benefits
beyond glycemic control.
AB - Obese-insulin resistance and type 2 diabetes mellitus (T2DM) have become global
health problems, and they are both associated with a higher risk of ischemic
heart disease. Although reperfusion therapy is the treatment to increase blood
supply to the ischemic myocardium, this intervention potentially causes cardiac
tissue damage and instigates arrhythmias, processes known as reperfusion injury.
Dipeptidyl peptidase 4 (DPP-4) inhibitors are glycemic control drugs commonly
used in T2DM patients. Growing evidence from basic and clinical studies
demonstrates that a DPP-4 inhibitor could exert cardioprotection and improve left
ventricular function by reducing oxidative stress, apoptosis, and increasing
reperfusion injury salvage kinase (RISK) activity. However, recent reports also
showed potentially adverse cardiac events due to the use of a DPP-4 inhibitor. To
investigate this disparity, future large clinical trials are essential in
verifying whether DPP-4 inhibitors are beneficial beyond their glycemic control
particularly for the ischemic heart in obese-insulin resistant subjects and T2DM
patients.
PMID- 26432494
TI - Accelerometer-determined physical activity and mortality in a national
prospective cohort study of adults at high risk of a first atherosclerotic
cardiovascular disease event.
PMID- 26432495
TI - Regulation of neuropathic pain behavior by amygdaloid TRPC4/C5 channels.
AB - Pain per se may increase anxiety and conversely, anxiety may increase pain.
Therefore, a positive feedback loop between anxiety and pain possibly contributes
to pain and suffering in some pathophysiological pain conditions, such as that
induced by peripheral nerve injury. Recent results indicate that transient
receptor channels 4 and 5 (TRPC4/C5) in the amygdala have anxiogenic effects in
rodents, while their role in chronic pain conditions is not known. Here, we
studied whether the amygdaloid TRPC4/C5 that are known to have anxiogenic
properties contribute to the maintenance of sensory or affective aspects of pain
in an experimental model of peripheral neuropathy. Rats with a spared nerve
injury (SNI) model of neuropathy in the left hind limb had a chronic cannula for
microinjections of drugs into the right amygdala or the internal capsule (a
control site). Sensory pain was assessed by determining mechanical
hypersensitivity with calibrated monofilaments and affective pain by determining
aversive place-conditioning. Amygdaloid treatment with ML-204, a TRPC4/C5
antagonist, produced a dose-related (5-10 MUg) antihypersensitivity effect,
without obvious side-effects. Additionally, amygdaloid administration of ML-204
reduced affective-like pain behavior. In the internal capsule, ML-204 had no
effect on hypersensitivity or affective-like pain in SNI animals. In healthy
controls, amygdaloid administration of ML-204 failed to influence pain behavior
induced by mechanical stimulation or noxious heat. The results indicate that the
amygdaloid TRPC4/C5 contribute to maintenance of pain hypersensitivity and pain
affect in neuropathy.
PMID- 26432496
TI - Pigmented ganglioglioma in a patient with chronic epilepsy and cortical
dysplasia.
AB - We report a rare case of a 22-year-old woman with biopsy-proven pigmented
ganglioglioma. The patient initially underwent a right temporal lobectomy for
intractable seizures at the age of 9 and remained seizure free for several years
but subsequently developed complex partial seizures. Due to enhancement of a left
mesial occipital lesion on preoperative MRI of the brain, the patient underwent a
left subdural electrode placement and simultaneous biopsy of the left mesial
occipital lesion. Biopsy results revealed a rare pigmented ganglioglioma, World
Health Organization Grade I. The seizure focus was identified in the left mesial
occipital lobe and the patient underwent tumor resection. An extensive literature
search revealed that our patient is the fourth case of pigmented ganglioglioma
described in the literature and was positive for BRAF V600E mutation by molecular
studies.
PMID- 26432497
TI - Rapid access point of care clinic for transient ischemic attacks and minor
strokes.
AB - We present 24months of prospective data from a new model of care for transient
ischemic attacks (TIA) and minor stroke, established at the Royal North Shore
Hospital, a tertiary teaching hospital in Sydney, Australia. Prior to 2011,
approximately 200 patients were admitted to our emergency department (ED)
annually, following presentation with a suspected TIA. These patients had an
average length of stay of 5.3days. Following the establishment of a twice weekly
multidisciplinary, one stop, stroke prevention and hospital avoidance clinic, all
patients with suspected TIA were investigated and treated as outpatients. There
was an average time to clinic from the initial presentation in the ED of 3.9days.
Symptoms that were highly suggestive of TIA were seen in 47% of patients, and an
additional 14% had MRI-confirmed acute stroke. In total, 405 patients were
referred to the clinic, saving 2146.5 inpatient bed days and approximately
AUD$1,180,575. Our model of care for patients with suspected TIA provides early
access for investigation, treatment and management of the risk factors. The rapid
access TIA clinic is highly cost effective and provides a transferable model of
care for other health districts with similar patient loads and cost structures.
PMID- 26432498
TI - Running in the family: A rare diagnosis of familial papillary thyroid cancer.
AB - INTRODUCTION: Whilst inherited medullary thyroid cancer has been extensively
reported, familial non-medullary thyroid cancer is a rare and less well described
clinical entity. Familial forms of the disease demonstrate more aggressive
features than sporadic non-medullary thyroid cancer. PRESENTATION OF CASE: A 54
year old lady was referred with globus on a background of a longstanding goitre.
Three first degree relatives had a history of non-medullary thyroid carcinoma.
Investigations revealed a papillary thyroid carcinoma and the patient proceeded
to total thyroidectomy and ipsilateral Level VI neck dissection, followed by
adjuvant radioiodine ablation. DISCUSSION: Familial papillary thyroid carcinoma
syndrome is defined as three or more first degree relatives diagnosed with the
disease in the absence of other known associated syndromes. It is often
associated with the presence of benign thyroid disorders, and is characterised by
the early onset of multi-focal bilateral locally advanced tumours. CONCLUSION:
Familial papillary thyroid cancer is a rare clinical entity but should be
considered where >=3 first degree relatives are diagnosed with non-medullary
thyroid cancer. It is necessary to exclude other familial tumour syndromes to
make the diagnosis. It demonstrates more aggressive features with higher rates of
local recurrence than its sporadic counterpart, and therefore mandates more
aggressive management than might otherwise be indicated. Screening of first
degree relatives should be considered. SUMMARY: The case of a 54 year old female
diagnosed with familial non-medullary thyroid carcinoma is reported.
PMID- 26432499
TI - Clinical Weighting of Drug-Drug Interactions in Hospitalized Elderly.
AB - Adverse drug reactions impact on patient health, effectiveness of pharmacological
therapy and increased health care costs. This investigation intended to detect
the most critical drug-drug interactions in hospitalized elderly patients,
weighting clinical risk. We conducted a cross-sectional study between January and
April 2014; all patients 70 years or older, hospitalized for >24 hr and
prescribed at least one medication were included in the study. Drug-drug
interactions were estimated by combining Stockley's, Hansten and Tatro drug
interactions. Drug-drug interactions were weighted using a risk-analysis method
based on failure modes, effects and criticality analysis. We calculated a
criticality index for each drug involved in the drug-drug interactions based on
the severity of the interaction mechanism, the frequency the drug was involved in
drug-drug interactions and the risk of drug-drug interactions in patients with
impaired renal function. The average number of drugs consumed in the hospital was
6 +/- 2.69, involving 160 active ingredients. The most frequent were as follows:
Furosemide, followed by Enalapril. Of drug-drug interactions, 2% were classified
as contraindicated, 14% advised against and 83% advised caution during the
hospital stay. Thirty-four drug-drug interactions were assessed, of which 23 were
pharmacodynamic drug-drug interactions and 12 were pharmacokinetic drug-drug
interactions (1 was both). The clinical risk calculated for each drug-drug
interaction included heparins + non-steroidal anti-inflammatory drugs (NSAIDs) or
Digoxin + Calcium Gluconate, cases which are pharmacodynamic drug-drug
interactions with agonist effect and clinical risk of bleeding, one of the most
common clinical risks in the hospital. An index of clinical risk for drug-drug
interactions can be calculated based on severity by the interaction mechanism,
the frequency that the drug is involved in drug-drug interactions and the risk of
drug-drug interactions in an elderly patient with impaired renal function.
PMID- 26432500
TI - Single substitution in bacteriophage T4 RNase H alters the ratio between its exo-
and endonuclease activities.
AB - The article describes substitutions in bacteriophage T4 RNase H which provide so
called das-effect. Phage T4 DNA arrest suppression (das) mutations have been
described to be capable of partially suppressing the phage DNA arrest phenotype
caused by a dysfunction in genes 46 and/or 47 (also known as Mre11/Rad50
complex). Genetic mapping of das13 (one of the das mutations) has shown it to be
in the region of the rnh gene encoding RNase H. Here we report that Das13 mutant
of RNase H has substitutions of valine 43 and leucine 242 with isoleucines. To
investigate the influence of these mutations on RNase H nuclease properties we
have designed a novel in vitro assay that allows us to separate and quantify exo-
or endonuclease activities of flap endonuclease. The nuclease assay in vitro
showed that V43I substitution increased the ratio between
exonuclease/endonuclease activities of RNase H whereas L242I substitution did not
affect the nuclease activity of RNase H in vitro. However, both mutations were
necessary for the full das effect in vivo. Molecular modelling of the nuclease
structure suggests that V43I substitution may lead to disposition of H4 helix,
responsible for the interaction with the first base pairs of 5'end of branched
DNA. These structural changes may affect unwinding of the first base pairs of
gapped or nicked DNA generating a short flap and therefore may stabilize the DNA
enzyme complex. L242I substitution did not affect the structure of RNase H and
its role in providing das-effect remains unclear.
PMID- 26432501
TI - An integrated network model of psychotic symptoms.
AB - The full body of research on the nature of psychosis and its determinants
indicates that a considerable number of factors are relevant to the development
of hallucinations, delusions, and other positive symptoms, ranging from
neurodevelopmental parameters and altered connectivity of brain regions to
impaired cognitive functioning and social factors. We aimed to integrate these
factors in a single mathematical model based on network theory. At the
microscopic level this model explains positive symptoms of psychosis in terms of
experiential equivalents of robust, high-frequency attractor states of neural
networks. At the mesoscopic level it explains them in relation to global brain
states, and at the macroscopic level in relation to social-network structures and
dynamics. Due to the scale-free nature of biological networks, all three levels
are governed by the same general laws, thereby allowing for an integrated model
of biological, psychological, and social phenomena involved in the mediation of
positive symptoms of psychosis. This integrated network model of psychotic
symptoms (INMOPS) is described together with various possibilities for
application in clinical practice.
PMID- 26432502
TI - Computational modeling of psychiatric illnesses via well-defined
neurophysiological and neurocognitive biomarkers.
AB - A good deal of recent research has centered on the identification of biomarkers
and endophenotypic measures of psychiatric illnesses using in vivo and in vitro
studies. This is understandable, as these measures-as opposed to complex clinical
phenotypes-may be more closely related to neurobiological and genetic
vulnerabilities. However, instantiation of such biomarkers using computational
models-in silico studies-has received less attention. This approach could become
increasingly important, given the wealth of detailed information produced by
recent basic neuroscience research, and increasing availability of high capacity
computing platforms. The purpose of this review is to survey the current state of
the art of research in this area. We discuss computational approaches to
schizophrenia, bipolar disorder, Alzheimer's disease, fragile X syndrome and
autism, and argue that it represents a promising and underappreciated research
modality. In conclusion, we outline specific avenues for future research; also,
potential uses of in silico models to conduct "virtual experiments" and to
generate novel hypotheses, and as an aid in neuropsychiatric drug development are
discussed.
PMID- 26432503
TI - Implicit measures of "wanting" and "liking" in humans.
AB - Incentive Sensitization Theory (IST; e.g., Robinson and Berridge, 1993. Brain
Res. Rev., 18, 291; Robinson and Berridge, 2003 Trends Neurosci., 26, 507)
suggests that a common dopamine system that deals with incentive salience
attribution is affected by different types of drugs. Repeated drug use will
sensitize this neural system, which means that drugs increasingly trigger the
experience of incentive salience or "wanting". Importantly, Robinson and Berridge
stress that there is a dissociation between drug "wanting" (the unconscious
attribution of incentive salience) and drug "liking" (the unconscious hedonic
experience when one consumes drugs). Whereas the former plays an essential role
in the development and maintenance of drug addiction, the latter does not.
Although this model was based mainly on research with non-human animals, more
recently the dissociation between "wanting" and "liking" has been examined in
humans as well. A widely used and promising means of studying these processes are
behavioral implicit measures such as the Implicit Association Test (IAT), the
Approach-Avoidance Task (AAT), different types of Stimulus-Response Compatibility
(SRC) tasks, and Affective Simon Tasks (AST). IST makes the clear prediction that
(1) there should be a positive correlation between indices of "wanting" (e.g.,
drug consumption) and implicit "wanting" scores. Similarly, there should be a
positive correlation between indices of "liking" (e.g., various expressions of
subjective pleasure) and implicit "liking" scores; (2) there should be higher
"wanting" scores in substance abusers or frequent substance users compared to non
users or infrequent users, and there should be no differences in "liking" between
these groups (or even less "liking" in frequent substance users); (3)
manipulations of "wanting" should affect implicit "wanting" scores whereas
manipulations of "liking" should affect implicit "liking" scores. However,
studies that tested these hypotheses did not produce equivocal results. To shed
light on these discrepancies, we first discuss the different definitions of
"wanting" and "liking" and the different tests that have been used to assess
these processes. Then, we discuss whether it is reasonable to assume that these
tests are valid measures of "wanting" and "liking" and we review correlational,
quasi-experimental, and experimental studies that inform us about this issue.
Finally, we discuss the future potential of implicit measures in research on IST
and make several recommendations to improve both theory and methodology.
PMID- 26432504
TI - The mechanisms of spatial and temporal patterning of cell-edge dynamics.
AB - Adherent cells migrate and change their shape by means of protrusion and
retraction at their edges. When and where these activities occur defines the
shape of the cell and the way it moves. Despite a great deal of knowledge about
the structural organization, components, and biochemical reactions involved in
protrusion and retraction, the origins of their spatial and temporal patterns are
still poorly understood. Chemical signaling circuitry is believed to be an
important source of patterning, but recent studies highlighted mechanisms based
on physical forces, motion, and mechanical feedback.
PMID- 26432505
TI - Prior stress exposure increases pain behaviors in a rat model of full thickness
thermal injury.
AB - Thermal burns among individuals working in highly stressful environments, such as
firefighters and military Service Members, are common. Evidence suggests that pre
injury stress may exaggerate pain following thermal injury; however current
animal models of burn have not evaluated the potential influence of pre-burn
stress. This sham-controlled study evaluated the influence of prior stress
exposure on post-burn thermal and mechanical sensitivity in male Sprague-Dawley
rats. Rats were exposed to 20 min of inescapable swim stress or sham stress once
per day for three days. Exposure to inescapable swim stress (1) increased the
intensity and duration of thermal hyperalgesia after subsequent burn and (2)
accelerated the onset of thermal hyperalgesia and mechanical allodynia after
subsequent burn. This stress-induced exacerbation of pain sensitivity was
reversed by pretreatment and concurrent treatment with the serotonin
norepinephrine reuptake inhibitor (SNRI) duloxetine. These data suggest a better
understanding of mechanisms by which prior stress augments pain after thermal
burn may lead to improved pain treatments for burn survivors.
PMID- 26432506
TI - Pessimism and the risk for coronary heart disease among middle-aged and older
Finnish men and women: a ten-year follow-up study.
AB - BACKGROUND: Despite the growth in knowledge about coronary heart disease (CHD)
risk factors, and the advances made in preventing and treating them, the
incidence of CHD is still notably quite high. Research has concentrated on the
physiological factors that present risks for CHD, but there is an increasing
amount of evidence for the connection of mental health, personal traits and CHD.
Data on the connection of disposition (optimism or pessimism) and CHD are
relatively scarce. The aim of this study was to investigate the long-term
connection between optimism, pessimism and the risk for having CHD. METHODS: This
was a ten-year prospective cohort study on a regional sample of three cohorts
aged 52-56, 62-66 and 72-76 years at baseline (N = 2815). The study groups were
personally interviewed four times (in 2002, 2005, 2008 and 2012). The revised
Life Orientation Test (LOT-R) was completed at the first appointment to determine
the level of dispositional optimism or pessimism. During the ten-year follow-up,
the incidence of new cases of coronary heart diseases was measured. The
association between dispositional optimism/pessimism and the incidence of CHD
during the follow-up was studied with logistic regression. RESULTS: Those who
developed coronary heart disease during the ten-year follow-up were significantly
more pessimistic at baseline than the other subjects. Using multivariate logistic
regression models separately for men and women, we noticed no elevated risk for
CHD in the pessimistic women compared to the non-pessimistic women. However,
among men in the highest quartile of pessimism, the risk for CHD was
approximately four-fold (OR 4.11, 95 % CI 1.68-11.04) that of the men in the
lowest quartile. Optimism did not seem to have any role in the risk for
developing CHD. DISCUSSION: Our main finding is that pessimism seemed to be a
clear risk factor for coronary heart disease in men even after adjusting for
classical well-known risk factors while optimism did not seem to be a protective
factor. Connection between pessimism and coronary heart disease was not
detectable among women. Similar gender differences between psychosocial factors
and overall well-being have been noticed in some earlier studies, too. The
mechanism of this gender difference is not fully understood. Differences between
men and women in somatic responses to stress found in earlier studies may at
least partly explain this phenomenon. The impact of optimism and pessimism on
cardiovascular disease has been studied earlier and several possible mechanisms
have been discovered but it seems clear that they cannot fully explain the
association. For example, optimists have healthier lifestyles which lowers the
risk for coronary heart disease, but pessimism was established to be a risk
factor for cardiovascular disease in our study even in logistic regressions
including the best known classical risk factors, e.g. smoking and high level of
blood glucose. According to our study it is important to pay attention also to
the psychosocial components in addition to the well-known risk factors when
planning the prevention of coronary heart disease. Measuring pessimism is quite
easy and it consumes very little time. Once the amount of pessimism is
ascertained, it is easier to define who is in the greatest need of preventive
actions concerning coronary heart disease. CONCLUSIONS: Pessimism seems to be a
substantial risk factor for CHD, and as an easily measured variable it might be a
very useful tool together with the well-known physiological risk factors to
determine the risk for developing CHD, at least among men.
PMID- 26432507
TI - Predictors and outcomes of delayed graft function after living-donor kidney
transplantation.
AB - Delayed graft function (DGF) following deceased donor kidney transplantation is
associated with inferior outcomes. Delayed graft function following living-donor
kidney transplantation is less common, but its impact on graft survival unknown.
We therefore sought to determine risk factors for DGF following living-donor
kidney transplantation and DGF's effect on living-donor kidney graft survival. We
analyzed living-donor kidney transplants performed between 2000 and 2014 in the
UNOS dataset. A total of 64 024 living-donor kidney transplant recipients were
identified, 3.6% developed DGF. Cold ischemic time, human leukocyte antigen
mismatch, donor age, panel reactive antibody, recipient diabetes, donor and
recipient body mass index, recipient race and gender, right nephrectomy, open
nephrectomy, dialysis status, ABO incompatibility, and previous transplants were
independent predictors of DGF in living-donor kidney transplants. Five-year graft
survival among living-donor kidney transplant recipients with DGF was
significantly lower compared with graft survival in those without DGF (65% and
85%, respectively, P < 0.001). DGF more than doubled the risk of subsequent graft
failure (hazard ratio = 2.3, 95% confidence interval: 2.1-2.6; P < 0.001). DGF
after living-donor kidney transplantation is associated with inferior allograft
outcomes. Minimizing modifiable risk factors may improve outcomes in living-donor
kidney transplantation.
PMID- 26432508
TI - Treatment Rationale and Study Design for the JUNIPER Study: A Randomized Phase
III Study of Abemaciclib With Best Supportive Care Versus Erlotinib With Best
Supportive Care in Patients With Stage IV Non-Small-Cell Lung Cancer With a
Detectable KRAS Mutation Whose Disease Has Progressed After Platinum-Based
Chemotherapy.
AB - This clinical trial summary provides the background and rationale for the JUNIPER
study (NCT02152631). JUNIPER is a randomized study of abemaciclib (200 mg orally
every 12 hours) with best supportive care (BSC) versus erlotinib (150 mg orally
every 24 hours) with BSC in patients with stage IV non-small-cell lung cancer
(NSCLC) whose tumors have detectable Kirsten rat sarcoma (KRAS) mutations and
whose disease has progressed after platinum-based chemotherapy and 1 other
previous therapy, or who are not eligible for further chemotherapy. Approximately
550 patients will be randomized in a 3:2 ratio and stratified according to number
of previous chemotherapy regimens (1 vs. 2), Eastern Cooperative Oncology Group
performance status (0 vs. 1), sex (male vs. female), and KRAS mutation (G12C vs.
others). Erlotinib was chosen as the control arm, because it is the only agent
indicated for second- and third-line therapy in advanced NSCLC. Treatment will
continue until disease progression or unacceptable toxicity occurs, with
assessments every 28 days, followed by short-term and long-term follow-up. The
coprimary efficacy objectives of this study are progression-free survival (PFS)
and overall survival (OS); secondary objectives are overall response rate,
changes in patient-reported pain and disease-related symptoms, changes in health
status, resource utilization, safety and tolerability, and
pharmacokinetics/pharmacodynamics. This design has 80% power to detect OS hazard
ratio (HR) of 0.75 (type I error 0.045) and PFS HR of 0.67 (type I error 0.005).
If the coprimary objectives (OS and PFS) are achieved, this study will provide a
new alternative third-line treatment option for patients with NSCLC whose tumors
have detectable KRAS mutations.
PMID- 26432509
TI - The European Food Safety Authority recommendation for polyunsaturated fatty acid
composition of infant formula overrules breast milk, puts infants at risk, and
should be revised.
AB - The European Food Safety Authority (EFSA) has concluded from a limited review of
the literature that although docosahexaenoic acid (DHA) is required for infant
formula, arachidonic acid is not required "even in the presence of DHA" (EFSA
Journal, 12 (2014) 3760). This flawed opinion is grounded in human trials which
tested functionality of DHA in neural outcomes and included arachidonic acid
ostensibly to support growth. The EFSA report mistakes a nutrient ubiquitous in
the diets of newborn infants, through breast milk and with wide-ranging health
and neurodevelopmental effects, for an optional drug targeted to a particular
outcome that is properly excluded when no benefit is found for that particular
outcome. Arachidonic acid has very different biological functions compared to
DHA, for example, arachidonic acid has unique functions in the vasculature and in
specific aspects of immunity. Indeed, the overwhelming majority of trials include
both DHA and arachidonic acid, and test development specific to DHA such as
neural and visual development. DHA suppresses membrane arachidonic acid
concentrations and its function. An infant formula with DHA and no arachidonic
acid runs the risk of cardio and cerebrovascular morbidity and even mortality
through suppression of the favorable oxylipin derivatives of arachidonic acid.
The EFSA recommendation overruling breast milk composition should be revised
forthwith, otherwise being unsafe, ungrounded in most of the evidence, and
risking lifelong disability.
PMID- 26432510
TI - Analysis of hospital cost outcome of DHA-rich fish-oil supplementation in
pregnancy: Evidence from a randomized controlled trial.
AB - OBJECTIVE: Recent research emphasized the nutritional benefits of omega-3 long
chain polyunsaturated fatty acids (LCPUFAs) during pregnancy. Based on a double
blind randomised controlled trial named "DHA to Optimize Mother and Infant
Outcome" (DOMInO), we examined how omega 3 DHA supplementation during pregnancy
may affect pregnancy related in-patient hospital costs. METHOD: We conducted an
econometric analysis based on ordinary least square and quantile regressions with
bootstrapped standard errors. Using these approaches, we also examined whether
smoking, drinking, maternal age and BMI could influence the effect of DHA
supplementation during pregnancy on hospital costs. RESULTS: Our regressions
showed that in-patient hospital costs could decrease by AUD92 (P<0.05) on average
per singleton pregnancy when DHA supplements were consumed during pregnancy. Our
regression results also showed that the cost savings to the Australian public
hospital system could be between AUD15 - AUD51 million / year. CONCLUSION: Given
that a simple intervention like DHA-rich fish-oil supplementation could generate
savings to the public, it may be worthwhile from a policy perspective to
encourage DHA supplementation among pregnant women.
PMID- 26432511
TI - Association between hospital procedure volume and risk of revision after total
hip arthroplasty: a population-based study within the Nordic Arthroplasty
Register Association database.
AB - OBJECTIVE: Outcome after total hip arthroplasty (THA) depends on several factors
related to the patient, the surgeon and the implant. It has been suggested that
the annual number of procedures per hospital affects the prognosis. We aimed to
examine if hospital procedure volume was associated with the risk of revision
after primary THA in the Nordic countries from 1995 to 2011. DESIGN: The Nordic
Arthroplasty Register Association database provided information about primary
THA, revision and annual hospital volume. Hospitals were divided into five volume
groups (1-50, 51-100, 101-200, 201-300, >300). The outcome of interest was risk
of revision 1, 2, 5, 10 and 15 years after primary THA. Multivariable regression
was used to assess the relative risk (RR) of revision. RESULTS: 417,687 THAs were
included. For the 263,176 cemented THAs no differences were seen 1 year after
primary procedure. At 2, 5, 10 and 15 years the four largest hospital volume
groups had a reduced risk of revision compared to group 1-50. After 10 years RR
was for volume group 51-100 0.79 (CI 0.65-0.95), group 101-200 0.76 (CI 0.61
0.95), group 201-300 0.74 (CI 0.57-0.96) and group >300 0.57 (CI 0.46-0.71). For
the uncemented THAs an association between hospital volume and risk of revision
were only present for hospitals producing 201-300 THAs per year, beginning at
years 2 through 5 and in all subsequent time intervals to 15 years. CONCLUSION:
Hospital procedure volume was associated with a long term risk of revision after
primary cemented THA. Hospitals operating 50 procedures or less per year had an
increased risk of revision after 2, 5, 10 and 15 years follow up.
PMID- 26432513
TI - Temporal changes in soil water repellency after a forest fire in a Mediterranean
calcareous soil: Influence of ash and different vegetation type.
AB - Forest fires usually modify soil water repellency (SWR), and its persistence and
intensity show a high variability both in space and time. This research studies
the evolution of SWR in a Mediterranean calcareous soil affected by a forest
fire, which occurred in Gorga (SE Spain) in July 2011, comparing the effect of
the main vegetation cover between pine (Pinus halepensis) and shrubs species
(Quercus coccifera, Rosmarinus officinalis, Cistus albidus, Erica arborea and
Brachypodium retusum) and the relationship with soil moisture content (SMC). Also
the study analyzed the effect of ash on SWR dynamics under field conditions. Six
plots were established on the fire-affected area and the unburned-control
adjacent area to monitoring SWR with the water drop penetration time (WDPT) test,
SMC through moist sensors (5cm depth) and three different ash treatments: ash
presence, ash absence and incorporation of ash into the soil. An immediate
increase of SWR was observed in the fire-affected area, mainly in pine plots. SWR
changes in control (unburned) plots were quite similar between different types of
vegetation influence, despite higher SWR values being observed on pine plots
during the study period. A noticeable decrease of SWR was observed during the
first months after fire in the affected areas, especially after the first rainy
period, both in pine and shrubs plots. SWR increase was registered in all plots,
and the highest levels were in March 2012 in burned pine plots. SWR decrease was
higher in plots where ash was removed. Fire-affected soils became wettable 1year
and a half after the fire.
PMID- 26432512
TI - Synovitis and the risk of knee osteoarthritis: the MOST Study.
AB - OBJECTIVE: To identify the independent relation of synovitis with incident
radiographic knee osteoarthritis (OA) after adjusting for other structural
factors known to cause synovitis. DESIGN: We examined MRIs from knees that
developed incident radiographic OA from the Multicenter Osteoarthritis Study
(MOST) and compared these case knees with controls that did not develop OA. We
examined baseline MRIs for knees developing OA at any time up to 84 months follow
up. We scored lesions in cartilage, meniscus, bone marrow and synovitis.
Synovitis scores were summed (0-9) across three regions, suprapatellar,
infrapatellar and intercondylar region, each of which was scored 0-3. After
bivariate analyses examining each factor's association with incidence, we carried
out multivariable regression analyses adjusting for age, sex, BMI, alignment and
cartilage and meniscal damage. RESULTS: We studied 239 case and 731 control
knees. In bivariate analyses, cartilage lesions, meniscal damage, synovitis and
bone marrow lesions were all risk factors for OA. After multivariable analyses,
synovitis was associated with incident OA. A higher synovitis score increased the
risk of incident OA (adjusted OR per unit increase 1.1; (95% CI 1.0, 1.2, P =
.02)), but increased risk was associated only with synovitis scores of >=3
(adjusted OR 1.6; 95% CI 1.2, 2.1, P = .003). CONCLUSIONS: Synovitis, especially
when there is a substantial volume within the knee, is an independent cause of
OA.
PMID- 26432514
TI - Skin Testing in the Evaluation and Management of Carboplatin-Related
Hypersensitivity Reactions.
AB - Carboplatin-induced hypersensitivity reactions (HSRs) are a frequent occurrence
in patients being retreated for malignancy. The most common and severe reactions
are thought to be IgE mediated. Currently, skin testing is the only method used
clinically to identify individuals sensitized to carboplatin. Despite almost 20
years of clinical use, a standardized approach to skin testing and its use in the
management of carboplatin HSRs has not been well established. We review the
utility of carboplatin skin testing and discuss factors that influence the
interpretation of skin testing results. A risk stratification strategy using skin
testing and desensitization to manage patients with carboplatin HSRs is proposed.
PMID- 26432515
TI - Meta-xylene: identification of a new antigenic entity in hypersensitivity
reactions to local anesthetics.
PMID- 26432516
TI - Waddlia: An emerging pathogen and a model organism to study the biology of
chlamydiae.
AB - Waddlia chondrophila is an emerging pathogen associated with abortion in cattle.
In humans, a growing body of evidence supports its pathogenic role in miscarriage
and in respiratory tract infection. The human pathogenicity of W. chondrophila is
further supported by the presence of several virulence factors including a
catalase, a functional T3SS and several adhesins. Despite this medical
importance, no commercial tests are available and diagnostic of this strict
intracellular bacterium mainly relies on serology, PCR and immunohistochemistry.
So far, the epidemiology of W. chondrophila remains largely unexplored and
zoonotic, waterborne or interhuman transmission has been considered. Apart from
its pathogenic role, chlamydiologists are also interested in W. chondrophila in
order to better understand biological mechanisms conserved and shared with
Chlamydia spp. Indeed, W. chondrophila proved to be a useful model organism to
study the pathobiology of chlamydiae thanks to its rapid replication, its large
size allowing precise subcellular protein localization, as well as its growth in
Dictyostelium amoebae.
PMID- 26432517
TI - Development of dual fluorescent stage specific reporter strain of Toxoplasma
gondii to follow tachyzoite and bradyzoite development in vitro and in vivo.
AB - Toxoplasma gondii is a protozoan that infects 30% of humans as intermediate
hosts. T Sexual reproduction can occur only within the intestinal tract of
felines, however, infection in other mammals and birds is associated with asexual
replication and interconversion between the tachyzoite and bradyzoite stages.
Bradyzoites are slow growing forms found in tissue cysts in latent infection.
Recently, our group described the biological behavior of the EGS strain that
forms thick walled cysts spontaneously in tissue culture, constituting a useful
tool for examining the developmental biology of T. gondii. To further improve the
usefulness of this model, we constructed genetically modified EGS parasites that
express fluorescent tags under the control of stage specific promoters. The
promoter regions for SAG-1 (tachyzoite specific), BAG-1 and LDH-2 (bradyzoite
specific) were amplified by PCR and plasmids were constructed with mCherry (redT)
and sfGFP (greenB) sequences, respectively. Strains of parasites were selected
using FACS to arrive at single fluorescent and dual fluorescent strains of EGS
expressing tags in a stage specific manner. In cell cultures, vacuoles labeled by
immunofluorescence assay using anti-CST-1 a marker for T. gondii cyst wall
contained parasites that were positive for BAG1-GFP and negative for SAG1
mCherry. Tachyzoites and bradyzoites harvested from the mice expressed stage
specific mCherry and GFP proteins, respectively. These new dual fluorescent
transgenic EGS strains are a promising tool to elucidate the mechanisms of T.
gondii differentiation both in vitro and in vivo.
PMID- 26432518
TI - Evaluation of a new serological test for the detection of anti-Coxiella and anti
Rickettsia antibodies.
AB - Coxiella burnetii and members of the genus Rickettsia are obligate intracellular
bacteria. Since cultivation of these organisms requires dedicated techniques,
their diagnosis usually relies on serological or molecular biology methods.
Immunofluorescence is considered the gold standard to detect antibody-reactivity
towards these organisms. Here, we assessed the performance of a new automated
epifluorescence immunoassay (InoDiag) to detect IgM and IgG against C. burnetii,
Rickettsia typhi and Rickettsia conorii. Samples were tested with the InoDiag
assay. A total of 213 sera were tested, of which 63 samples from Q fever, 20 from
spotted fever rickettsiosis, 6 from murine typhus and 124 controls. InoDiag
results were compared to micro-immunofluorescence. For acute Q fever, the
sensitivity of phase 2 IgG was only of 30% with a cutoff of 1 arbitrary unit
(AU). In patients with acute Q fever with positive IF IgM, sensitivity reached
83% with the same cutoff. Sensitivity for chronic Q fever was 100% whereas
sensitivity for past Q fever was 65%. Sensitivity for spotted Mediterranean fever
and murine typhus were 91% and 100%, respectively. Both assays exhibited a good
specificity in control groups, ranging from 79% in sera from patients with
unrelated diseases or EBV positivity to 100% in sera from healthy patients. In
conclusion, the InoDiag assay exhibits an excellent performance for the diagnosis
of chronic Q fever but a very low IgG sensitivity for acute Q fever likely due to
low reactivity of phase 2 antigens present on the glass slide. This defect is
partially compensated by the detection of IgM. Because it exhibits a good
negative predictive value, the InoDiag assay is valuable to rule out a chronic Q
fever. For the diagnosis of rickettsial diseases, the sensitivity of the InoDiag
method is similar to conventional immunofluorescence.
PMID- 26432519
TI - Comparison of clinical and laboratory characteristics of patients fulfilling
criteria for proven and probable human granulocytic anaplasmosis.
AB - To assess the value of clinical definitions for human granulocytic anaplasmosis
(HGA) epidemiological, clinical and laboratory findings in 50 adult patients with
proven HGA (Anaplasma phagocytophilum isolated from blood, and/or positive PCR
result, and/or seroconversion or >=4-fold change in serum IFA antibody titres to
A. phagocytophilum) and 46 patients with probable HGA (demonstration of serum
antibodies to A. phagocytophilum in titres >=1:256) were compared. Patients with
proven HGA were older (55 versus 43.5 years; p = 0.001), were more often treated
with doxycycline (31/50, 62% versus 11/46, 23.9%; p < 0.001), more frequently
reported chills (40/50, 80% versus 17/46, 36.9%; p < 0.001), myalgia (37/50, 74%
versus 21/46, 45.7%; p = 0.005) and cough (10/50, 20% versus 2/46, 4.4%; p =
0.02), and had more often abnormal laboratory findings such as thrombocytopenia
(45/50, 90% versus 22/46, 47.8%; p < 0.001), abnormal liver function test results
(45/50, 87% versus 22/46, 47.8%; p < 0.001), leukopenia (38/50, 76% versus 21/46,
45.7%; p = 0.002) and elevated serum CRP concentration (48/50, 96% versus 31/46,
67.4%; p < 0.001). The dissimilarities imply that in some patients fulfilling
criteria for probable HGA the signs and symptoms most likely are not the result
of a recent infection with A. phagocytophilum and indicate that clinical
definitions used in the present study have a distinctive value.
PMID- 26432520
TI - Genomic signatures in B-cell lymphoma: How can these improve precision in
diagnosis and inform prognosis?
AB - Current genomic technologies have immensely improved disease classification and
prognostication of major subtypes of B-cell lymphomas. This novel genetic
information has not only aided in diagnosis, but has also revealed a landscape of
critical molecular events that determine the biological and clinical behavior of
a lymphoma. In this review, we summarized the genetic characteristics of major
subtypes of B-cell lymphomas, including diffuse large B cell lymphoma (DLBCL),
follicular lymphoma (FL), Burkitt lymphoma (BL), and mantle cell lymphoma (MCL).
We illustrated how genomic profiling had identified molecular subgroups in DLBCL
with varied clinical outcomes, and how a subset of genes defined prognosis in MCL
and aided in BL diagnoses. We also highlighted some Phase II/III clinical trials
using new therapeutic agents to determine clinical efficacy in novel molecular
subgroups with distinct gene expression patterns. We believe that refinement of
genomic signatures will require more intensive efforts from the biomedical
research community to improve targeted therapy designs and bring a substantial
change in the treatment decisions. In the next era of genomic medicine, we
anticipate that a clinically and biologically relevant molecular profile of each
tumor will be obtained at diagnosis to guide therapy.
PMID- 26432521
TI - An examination of factors related to aspiration and silent aspiration in older
adults requiring long-term care in rural Japan.
AB - Swallowing disorders are a growing problem among the elderly in long-term care
(LTC), and they can cause aspiration pneumonia. In order to detect swallowing
disorders early, simple tools are needed to assess aspiration and silent
aspiration (SA). To compile a sample of elderly people requiring LTC, and
categorise them as having suspected aspiration and/or SA using simple screening
tools. In addition, oral ability, severity of dementia, vital functions and
nutritional status were compared in these groups. A total of 393 elderly people
in LTC (89 men and 304 women; age ranging from 65 to 100 years) were included in
the study. The modified water swallow test, cervical auscultation and cough test
were used to assess swallowing function. The participants were categorised as
having suspected aspiration and/or SA, and the following assessments were
performed: (i) oral ability (lips function, tongue function, rinsing and gargling
ability), (ii) dementia severity, (iii) vital functions and (iv) nutritional
status. Suspected aspiration was apparent in 50.5% of patients, of which 24.0%
had suspected SA. Those with suspected aspiration showed worsened oral ability,
dementia severity, vital functions and nutritional status. Similarly, those with
suspected SA showed worsened dementia severity, vital functions and nutritional
status. Logistic regression analysis revealed that lip closure, lingual movement
and rinsing ability were significantly associated with suspected aspiration.
Dementia severity was the best predictor of suspected SA. Simple screening tools
can be used to identify suspected aspiration and SA, which may facilitate early
detection of aspiration pneumonia or swallowing disorder risk.
PMID- 26432522
TI - Erratum for Gjessing et al., Salmon Gill Poxvirus, the Deepest Representative of
the Chordopoxvirinae.
PMID- 26432525
TI - Monitoring Dynamics of DNA Methylation at Single-Cell Resolution during
Development and Disease.
AB - DNA methylation is a broadly studied epigenetic modification that is essential
for normal mammalian development. Over the years, numerous methodologies were
developed trying to cope with the intrinsic challenge of reading the "second
dimension" epigenetic code. The recent rapid expansion of sequencing technologies
has made it possible to fully chart the methylation landscape of different cell
types at single-base resolution. Surprisingly, accumulating data suggest that, in
addition to the massive epigenome remodeling during early development, cell type
and tissue specification is associated with high levels of DNA methylation
dynamics at distal regulatory elements. However, current methods provide only a
static "snapshot" of DNA methylation, thus precluding the study of real-time
methylation dynamics during cell fate changes. Here we review the principles of a
new approach that enables monitoring loci-specific DNA methylation dynamics at
single-cell resolution. We also discuss potential applications and promises for
implementing this methodology to study DNA methylation changes during development
and disease.
PMID- 26432526
TI - Modulating the Genomic Programming of Adipocytes.
AB - The ability to modify the transcriptional program in response to external signals
provides a way for mammalian cells to alter their biological fate and properties,
thereby adapting to changes in the environment. Adipocytes are excellent examples
of differentiated cells that possess a striking transcriptional plasticity when
exposed to physiological and metabolic stimuli. In our work, we have focused on
understanding the processes responsible for modulating the genomic programming in
response to different external signals. Thus, we have shown that browning of
human adipocytes with rosiglitazone, an antidiabetic agonist of the key adipocyte
transcription factor peroxisome proliferator-activated receptor gamma
(PPARgamma), involves redistribution of PPARgamma binding to form browning
selective PPARgamma super-enhancers that drive expression of key browning genes.
These include genes encoding transcriptional regulators, such as Kruppel-like
factor 11 (KLF11) that are essential for modulating the genomic program in white
adipocytes to induce browning. Furthermore, we have shown that acute suppression
of adipocyte genes by the proinflammatory cytokine, tumor necrosis factor (TNF),
involves redistribution of cofactors to enhancers activated by the master
inflammatory regulator, nuclear factor kappa-light-chain-enhancer of activated B
cells (NF-kappaB). Interestingly, this redistribution occurs selectively from
enhancers with high-cofactor occupancies, thereby predominantly affecting super
enhancers and their associated genes. We propose that this is a general mechanism
contributing to transcriptional repression associated with activation of signal
dependent transcription factors.
PMID- 26432527
TI - ACC/AHA/STS Statement on the Future of Registries and the Performance Measurement
Enterprise: A Report of the American College of Cardiology/American Heart
Association Task Force on Performance Measures and The Society of Thoracic
Surgeons.
PMID- 26432528
TI - Mortality reduction from gastric cancer by endoscopic and radiographic screening.
AB - To evaluate mortality reduction from gastric cancer by endoscopic screening, we
undertook a population-based cohort study in which both radiographic and
endoscopic screenings for gastric cancer have been carried out. The subjects were
selected from the participants of gastric cancer screening in two cities in
Japan, Tottori and Yonago, from 2007 to 2008. The subjects were defined as
participants aged 40-79 years who had no gastric cancer screening in the previous
year. Follow-up of mortality was continued from the date of the first screening
to the date of death or up to December 31, 2013. A Cox proportional hazards model
was used to estimate the relative risk (RR) of gastric cancer incidence, gastric
cancer death, all cancer deaths except gastric cancer death, and all-causes death
except gastric cancer death. The number of subjects selected for endoscopic
screening was 9950 and that for radiographic screening was 4324. The subjects
screened by endoscopy showed a 67% reduction of gastric cancer compared with the
subjects screened by radiography (adjusted RR by sex, age group, and resident
city = 0.327; 95% confidence interval [CI], 0.118-0.908). The adjusted RR of
endoscopic screening was 0.968 (95%CI, 0.675-1.387) for all cancer deaths except
gastric cancer death, and 0.929 (95%CI, 0.740-1.168) for all-causes death except
gastric cancer death. This study indicates that endoscopic screening can reduce
gastric cancer mortality by 67% compared with radiographic screening. This is
consistent with previous studies showing that endoscopic screening reduces
gastric cancer mortality.
PMID- 26432529
TI - Introduction: Ejaculatory problems and male infertility.
AB - There are a variety of dysfunctions of the ejaculatory process which may
negatively impact male fertility but are not commonly discussed. The meanings of
the terms used to describe these conditions are often unclear. This month's Views
and Reviews define the commonly used and confused terms. The initial article
explains normal male function with an emphasis on the ejaculatory process.
Following articles discuss the causes, evaluation and management of the male with
ejaculatory dysfunction.
PMID- 26432530
TI - Management of the dry ejaculate: a systematic review of aspermia and retrograde
ejaculation.
AB - A dry ejaculate (aspermia), may occur either because of an inability to transport
semen (anejaculation) or because of an inability to ejaculate in an antegrade
direction (retrograde ejaculation). The treatment of aspermia varies with
underlying etiology and includes medical therapy with sympathomimetics, urinary
sperm retrieval, bladder neck reconstruction, prostatic massage, penile vibratory
stimulation, electroejaculation, and surgical sperm retrieval. A systematic
review of the current literature was performed for articles on ejaculatory
dysfunction related to dry ejaculate. However, the data are insufficient to allow
firm comparisons between treatment options. Treatments must be tailored to the
individual patient, and treatment decisions should involve consideration of ease
of administration, degree of invasiveness, and anticipated success.
PMID- 26432531
TI - Reducing capacities and redox potentials of humic substances extracted from
sewage sludge.
AB - Humic substances (HS) are redox active organic materials that can be extracted
from sewage sludge generated in wastewater treatment processes. Due to the poor
understanding of reducing capacity, redox potentials and redox active functional
groups of HS in sewage sludge, the potential contribution of sludge HS in
transformation of wastewater contaminants is unclear. In the present study, the
number of electrons donated or accepted by sewage sludge HS were quantified
before and after reduction by iron compounds that possess different redox
potentials and defined as the reducing capacity of the sewage sludge. In contrast
to previous studies of soil and commercial humic acids (HA), reduced sludge HA
showed a lower reducing capacity than that of native HA, which implies formation
of semiquinone radicals since the semiquinone radical/hydroquinone pair has a
much higher redox potential than the quinone/hydroquinone pair. It is novel that
reducing capacities of sludge HA were determined in the redox potential range
from -314 to 430 mV. The formation of semiquinone radicals formed during the
reduction of quinone moieties in sludge HA is shown by three-dimensional
excitation/emission matrix fluorescence spectroscopies information, increasing
fluorescence intensities and blue-shifting of the excitation/emission peak of
reduced sludge HA. Knowledge of sludge HS redox potentials and corresponding
reducing capacities makes it possible to predict the transformation of redox
active pollutants and facilitate manipulation and optimization of sludge loading
wastewater treatment processes.
PMID- 26432532
TI - High resistance of Tetrahymena thermophila to paraquat: Mitochondrial
alterations, oxidative stress and antioxidant genes expression.
PMID- 26432533
TI - Effects of kaolin particle films on the life span of an orb-weaver spider.
AB - Araniella cucurbitina (Araneae: Araneidae) is a widespread orb-weaver spider
commonly found in agroecosystems. Mineral particle films such as kaolin, due to
their protective or anti-feeding action, can represent an alternative to
pesticides, especially in organic farming systems, but little is known about its
effects on A. cucurbitina. Therefore, we tested the effect of kaolin sprays on
the life span of A. cucurbitina under laboratory conditions. Four treatments were
tested encompassing different exposure routes. Thus, kaolin sprays were applied
on (i) the surface, (ii) the prey (fly), (iii) the spider and (iv) both spider &
prey. A control group was tested with water in each treatment. Results showed
that sprays of kaolin significantly affected the survival of A. curcubitina when
applications were done on the surface and on both spider & prey registering a
reduction of 48% and 56%, respectively. Spiders in control obtained higher
probability of reaching alive at the end of the assay than those treated with
kaolin. Differences observed can be explained by the feeding behavior of the
species and may depend on the consumption of the web by the spider and the ratio
spider/fly for body size.
PMID- 26432534
TI - Responses of the CYP1A biomarker in Jenynsia multidentata and Phalloceros
caudimaculatus and evaluation of a CYP1A refractory phenotype.
AB - The level of cytochrome P450 1A (CYP1A) in fish is used as a typical
environmental biomarker for the presence of organic contaminants. We used RT-qPCR
to investigate CYP1A mRNA levels in the liver, gill and gonopodium of guppies
Jenynsia multidentata and Phalloceros caudimaculatus in wetlands within the Rio
Grande city (RG) which is under the influence of the Patos Lagoon Estuary (RS,
Brazil). The CYP1A mRNA levels evaluated in fish liver from two locations that
receive non-treated wastewater effluents (S3 and S4) and another locations near
an oil refinery (S6) and an industrial complex (S7), were higher than in
locations remote from those sites (S1, S2 and S5). The sum of 16 priority PAHs in
sediment confirmed high levels in S4 and S6 (3914.0 and 4414.0 ng g(-1) dw,
respectively) comparing to S7>S2>S3>S5>S1 (119.3, 66.3, 62.8, 16.4 and 1.7 ng g(
1) dw). J. multidentata from sites S1 to S4 that were transferred to the
laboratory exhibited CYP1A induction after 24 h waterborne exposure to 1 uM
betanaphtoflavone (BNF) in all organs compared to controls, except in the liver
of fish from site S4. This lack of CYP1A induction by BNF indicates a CYP1A
refractory phenotype in guppy. Although this characteristic possibly involves the
alteration in AHR signaling or control, the mechanism of resistance is unknown.
The present study provides information about the use of the use of CYP1A in South
American guppies as an useful biomarker tool for environmental contamination
studies.
PMID- 26432535
TI - The effect of feed water dissolved organic carbon concentration and composition
on organic micropollutant removal and microbial diversity in soil columns
simulating river bank filtration.
AB - This study investigated organic micropollutant (OMP) biodegradation rates in
laboratory-scale soil columns simulating river bank filtration (RBF) processes.
The dosed OMP mixture consisted of 11 pharmaceuticals, 6 herbicides, 2
insecticides and 1 solvent. Columns were filled with soil from a RBF site and
were fed with four different organic carbon fractions (hydrophilic, hydrophobic,
transphilic and river water organic matter (RWOM)). Additionally, the effect of a
short-term OMP/dissolved organic carbon (DOC) shock-load (e.g. quadrupling the
OMP concentrations and doubling the DOC concentration) on OMP biodegradation
rates was investigated to assess the resilience of RBF systems. The results
obtained in this study imply that - in contrast to what is observed for managed
aquifer recharge systems operating on wastewater effluent - OMP biodegradation
rates are not affected by the type of organic carbon fraction fed to the soil
column, in case of stable operation. No effect of a short-term DOC shock-load on
OMP biodegradation rates between the different organic carbon fractions was
observed. This means that the RBF site simulated in this study is resilient
towards transient higher DOC concentrations in the river water. However, a
temporary OMP shock-load affected OMP biodegradation rates observed for the
columns fed with the river water organic matter (RWOM) and the hydrophilic
fraction of the river water organic matter. These different biodegradation rates
did not correlate with any of the parameters investigated in this study (cellular
adenosine triphosphate (cATP), DOC removal, specific ultraviolet absorbance
(SUVA), richness/evenness of the soil microbial population or OMP category
(hydrophobicity/charge).
PMID- 26432536
TI - Effect of UV irradiation on the proportion of organic chloramines in total
chlorine in subsequent chlorination.
AB - This study investigated the changes of chlorine species and proportion of organic
chloramines during the chlorination process after UV irradiation pretreatment in
drinking water. It was found that the UV pretreatment could enhance the
percentage of organic chloramines by increasing free chlorine consumption in the
chlorination of raw waters. The percentage of organic chloramines in total
chlorine increased with UV intensity and irradiation time in raw waters. However,
for the humic acid synthesized water, the percentage of organic chloramines
increased first and then decreased with the increase of UV irradiation time. The
value of SUVA declined in both raw and humic acid synthesized waters over the UV
irradiation time, which indicated that the decomposition of aromatic organic
matter by UV could be a contributor to the increase of free chlorine consumption
and organic chloramine proportion. The percentage of organic chloramines during
chlorination of raw waters after 30-min UV irradiation pretreatment varied from
20.2% to 41.8%. Total chlorine decreased obviously with the increase of nitrate
concentration, but the percentage of organic chloramines increased and was
linearly correlated to nitrate concentration.
PMID- 26432537
TI - Placental transfer of and infantile exposure to perchlorate.
AB - Fetuses and infants are vulnerable to perchlorate toxicity. We assessed fetal and
infantile exposure to perchlorate in two Chinese cities (Nanchang and Tianjin).
Perchlorate was widely found (82%-100%) in breast milk, dissolved infant formula,
infants' urine, maternal and cord blood samples. Perchlorate levels in infants'
urine (mean +/- standard deviation: 22.4 +/- 35.6 ng mL(-1)), breast milk (36.6
+/- 48.1 ng mL(-1)), and cord blood (3.18 +/- 3.83 ng mL(-1)) samples collected
from Nanchang and Tianjin were approximately an order of magnitude higher than
those reported for the U.S. Perchlorate concentrations in cord blood were
comparable to that in maternal blood, indicating that perchlorate is transferred
from mother to fetus through placenta. Among all infants providing urine samples,
the average daily intake of perchlorate (DOSEU) was estimated to be 1.17 +/- 1.57
MUg kg(-1) bw d(-1), and 40% of these infants had DOSEU exceeding the RfD (0.7
MUg kg(-1) bw d(-1)) recommended by U.S. EPA. However, approximately 70% of
exclusively breast-fed infants had perchlorate exposure dose via breast milk
exceeding the RfD. For breast-fed infants, breast milk was the overwhelmingly
predominant exposure pathway; while infant formula and indoor dust ingestion were
major perchlorate exposure sources for formula-fed infants. To our knowledge,
this is the first report to assess the fetal and infantile exposure to
perchlorate in China.
PMID- 26432538
TI - Simulating CO2 leakages from CCS to determine Zn toxicity using the marine
microalgae Pleurochrysis roscoffensis.
AB - Due to the current climate change and ocean acidification, a new technology for
CO2 mitigation has been proposed, the Carbon dioxide Capture and Storage (CCS).
However, there is an ecological risk associated with potential CO2 leakages from
the sub-seabed storages sites. To evaluate the effects related to CO2 leakages,
laboratory-scales experiments were performed using the marine microalgae
Pleurochrysis roscoffensis. Five Zn concentrations were tested at different pHs
to study Zn toxicity under acidified conditions. Seawater was collected and
submitted to acidification by means of CO2 injection and by HCl addition. Results
showed differences between both acidification techniques: while microalgae growth
was enhanced by CO2 supply, reaching the optimal growth at pH 6.5 and full
inhibition at pH 5.5, HCl acidification growth was inhibited at pH 6.5. Although
small concentrations of Zn were positive for P. roscoffensis growth, Zn toxicity
increased at lower pHs, and more severely on samples acidified with HCl. The
conclusions obtained in this work are useful to address the potential effects on
the marine ecosystem related to changes in metal bioavailability during CO2
leakages scenarios.
PMID- 26432539
TI - Interleukin-17, oxidative stress, and inflammation: role of melatonin during
Trypanosoma cruzi infection.
AB - Although the exact etiology of Chagas' disease remains unknown, the inflammatory
process and oxidative stress are believed to be the main contributors to the
dysfunction and pathogenesis during chronic Trypanosoma cruzi infection. Our
hypothesis is that melatonin administered for 2 months daily could modulate the
oxidative stress and the inflammatory response during the chronic infection. Flow
cytometric analysis of macrophages and antigen-presenting cells (APC), expression
of RT1B as well as LFA-1 and MCP-1 in CD4(+) and CD8(+) T cells and levels of
interleukin-17A were assessed. The oxidative stress was evaluated through lipid
peroxidation (LPO) analysis on the plasma of thiobarbituric acid-reactive
substances (TBARS) and nitric oxide production. Decreased concentrations of
nitrite and TBARS were found in infected and melatonin-treated animals, as well
as a rising trend in the production of IL-17A as compared to infected and
untreated counterparts. A significant decrease was found in the percentages of
CD4(+) and CD8(+) T lymphocytes MCP-1 producers for infected and melatonin
treated rats. Reduced percentage of CD8(+) T cells producing LFA-1 was observed
in control and melatonin-treated animals as compared to untreated rats. The
cellular response of peritoneal APC cells and macrophages significantly dropped
in infected and treated animals. As an endpoint, the use of antioxidant compounds
such as melatonin emerges as a new and promising approach to control the
oxidative stress during the chronic Chagas' disease partially mediated through
the abrogation of LPO and the prevention of the inflammatory response and can be
used for further investigation on treatment trials for other infectious diseases.
PMID- 26432540
TI - Auditory interference control in children with learning disability: An
exploratory study.
AB - OBJECTIVES: The current study aimed to compare the auditory interference control
of participants with Learning Disability (LD) to a control group on two versions
of an auditory Stroop task. METHODS: A group of eight children with LD (clinical
group) and another group of eight typically developing children (control group)
served as participants. All the participants were involved in a semantic and a
gender identification-based auditory Stroop task. Each participant was presented
with eight different words (10 times) that were pre-recorded by a male and a
female speaker. The semantic task required the participants to ignore the
speaker's gender and attend to the meaning of the word, and vice-versa for the
gender identification task. The participants' performance accuracy and reaction
time (RT) was measured on both the tasks. RESULTS: Control group participants
significantly outperformed the clinical group participants on both the tasks with
regard to performance accuracy as well as RT. CONCLUSION: The results suggest
that children with LD have problems in suppressing irrelevant auditory stimuli
and focusing on the relevant auditory stimuli. This can be attributed to the
auditory processing problems in these children.
PMID- 26432541
TI - Cost-benefit analysis of targeted hearing directed early testing for congenital
cytomegalovirus infection.
AB - OBJECTIVES: In this study, we estimate an ex ante cost-benefit analysis of a Utah
law directed at improving early cytomegalovirus (CMV) detection. STUDY DESIGN: We
use a differential cost of treatment analysis for publicly insured CMV-infected
infants detected by a statewide hearing-directed CMV screening program. METHODS:
Utah government administrative data and multi-hospital accounting data are used
to estimate and compare costs and benefits for the Utah infant population.
RESULTS: If antiviral treatment succeeds in mitigating hearing loss for one
infant per year, the public savings will offset the public costs incurred by
screening and treatment. If antiviral treatment is not successful, the program
represents a net cost, but may still have non-monetary benefits such as
accelerated achievement of diagnostic milestones. CONCLUSIONS: The CMV education
and treatment program costs are modest and show potential for significant cost
savings.
PMID- 26432543
TI - Hypoparathyroidism in Children.
PMID- 26432544
TI - Current concepts of shockwave therapy in chronic patellar tendinopathy.
PMID- 26432545
TI - Effects of shock wave therapy on glycosaminoglycan expression during bone
healing.
AB - BACKGROUND: Several cases of delayed bone consolidation have been treated with
extracorporeal shock wave therapy (ESWT) to improve bone healing and a key role
of the extracellular matrix glycosaminoglycans in osteogenesis has been
suggested. OBJECTIVE: In this study, we aimed to identify and quantify the amount
of sulfated glycosaminoglycans (GAG) and hyaluronic acid (HA) within rat femurs
following bone drilling and treatment with shock waves. METHODS: To identify and
quantify the sulfated glycosaminoglycans (GAG) and hyaluronic acid (HA) within
rat femurs following bone drilling and ESWT, 50 male Wistar rats were evaluated.
The animals were divided into two groups, both of which were subjected to bone
drilling. One of the groups was treated with ESWT. The rats were sacrificed on
the 3rd, 7th, 14th, 21st, and 28th day. GAG presence was analyzed by agarose gel
electrophoresis with subsequent densitometry and ELISA. RESULTS AND DISCUSSION:
The content of sulfated GAGs increased significantly from the 3rd to the 28th day
(p = 0.002). Chondroitin sulfate was expressed more highly than the other GAGs.
HA content increased significantly at the 3rd day in animals treated with ESWT
compared to the control group (p = 0.003). CONCLUSION: ESWT stimulates of
sulfated glycosaminoglycans during bone healing and enhanced early expression of
HA compared to the control group.
PMID- 26432542
TI - Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis:
Lessons from mouse models.
AB - The growth hormone (GH) and its downstream mediator, the insulin-like growth
factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and
organ function. Serum levels of GH/IGF-1 rise during pubertal growth and
associate with peak bone acquisition, while during aging their levels decline and
associate with bone loss. The GH/IGF-1 axis was extensively studied in numerous
biological systems including rodent models and cell cultures. Both hormones act
in an endocrine and autocrine/paracrine fashion and understanding their distinct
and overlapping contributions to skeletal acquisition is still a matter of
debate. GH and IGF-1 exert their effects on osteogenic cells via binding to their
cognate receptor, leading to activation of an array of genes that mediate
cellular differentiation and function. Both hormones interact with other skeletal
regulators, such as sex-steroids, thyroid hormone, and parathyroid hormone, to
facilitate skeletal growth and metabolism. In this review we summarized several
rodent models of the GH/IGF-1 axis and described key experiments that shed new
light on the regulation of skeletal growth by the GH/IGF-1 axis.
PMID- 26432546
TI - A Cochrane systematic review and network meta-analysis comparing treatment
strategies aiming to decrease blood loss during liver resection.
AB - INTRODUCTION: Intraoperative haemorrhage remains one of the major risks during
liver resection, and perioperative blood loss and blood transfusion are important
factors affecting perioperative morbidity and mortality. The aim of this study is
to compare treatment strategies aiming to decrease blood loss during hepatectomy.
METHODS: A systematic review of the literature was performed to identify
randomised controlled trials reporting on the method of vascular occlusion,
parenchymal transection, and management of the cut surface during liver
resection. A Bayesian network meta-analysis was performed using WinBUGS. RESULTS:
Seven trials reporting on 496 participants randomised to seven treatment
strategies were analysed. Continuous vascular occlusion resulted in lower blood
loss compared to no vascular occlusion when parenchymal transection was performed
with clamp-crush and no fibrin sealant was used for the cut surface. People
undergoing liver resection by continuous vascular occlusion had decreased amounts
of blood transfused than people with intermittent vascular occlusion when
parenchymal transection was performed with clamp-crush and no fibrin sealant.
There was no significant difference in proportion of people transfused,
mortality, or hospital stay between the different strategies. There were
significantly more serious adverse events when surgery was performed using
radiofrequency dissecting sealer compared with standard clamp-crush method in the
absence of vascular occlusion and fibrin sealant. CONCLUSIONS: Continuous
vascular occlusion during hepatectomy results in decreased blood loss and
decreased blood transfusion requirements. Further studies are needed to compare
treatment strategies aiming to decrease blood loss, defined by their method of
vascular occlusion, parenchymal transection, and management of the cut surface.
PMID- 26432547
TI - The association between loss of ankle dorsiflexion range of movement, and hip
adduction and internal rotation during a step down test.
AB - A pattern of excessive hip adduction and internal rotation with medial deviation
of the knee has been associated with numerous musculo-skeletal dysfunctions.
Research into the role that ankle dorsiflexion (DF) range of motion (ROM) play in
lower limb kinematics is lacking. The objective of this cross-sectional,
observational study was to investigate the relationship between ankle DF ROM, and
hip adduction and hip internal rotation during a step-down test with and without
heel elevation in a healthy female population. Hip and ankle ROM was measured
kinematically using a ten-camera Optitrack motion analysis system. Thirty healthy
female participants (mean age = 20.4 years; SD = 0.9 years) first performed a
step-down test with the heel of the weight bearing foot flat on the step and then
with the heel elevated on a platform. Ankle DF, hip adduction and hip internal
rotation were measured kinematically for the supporting leg. Participants who had
17 degrees or less of ankle DF ROM displayed significantly more hip adduction
ROM (p = 0.001; Cohen's d effect size = 1.2) than the participants with more than
17 degrees of DF during the step-down test. Participants with limited DF ROM
showed a significant reduction in hip adduction ROM during the elevated-heel step
down test (p = 0.008). Hip internal rotation increased in both groups during the
EHSD compared to the step-down test (p > 0.05) Reduced ankle DF ROM is associated
with increased hip adduction utilised during the step-down test. Ankle DF should
be taken into account when assessing patients with aberrant frontal plane lower
limb alignment.
PMID- 26432548
TI - Reproductive management through integration of PGD and MPS-based noninvasive
prenatal screening/diagnosis for a family with GJB2-associated hearing
impairment.
AB - A couple with a proband child of GJB2 (encoding the gap junction protein connexin
26)-associated hearing impairment and a previous pregnancy miscarriage sought for
a reproductive solution to bear a healthy child. Our study aimed to develop a
customized preconception-to-neonate care trajectory to fulfill this clinical
demand by integrating preimplantation genetic diagnosis (PGD), noninvasive
prenatal testing (NIPT), and noninvasive prenatal diagnosis (NIPD) into the
strategy. Auditory and genetic diagnosis of the proband child was carried out to
identify the disease causative mutations. The couple then received in-vitro
fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD
was performed by short-tandem-repeat linkage analysis and Sanger sequencing of
GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a
singleton pregnancy. At the 13th week of gestation, genomic DNA (gDNA) from the
trio family and cell-free DNA (cfDNA) from maternal plasma were obtained for
assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD
showed the absence of chromosomal aneuploidy and GJB2-associated disease in the
fetus, which was later confirmed by invasive procedures and postnatal
genetic/auditory diagnosis. This strategy successfully prevented the transmission
of hearing impairment in the newborn, thus providing a valuable experience in
reproductive management of similar cases and potentially other monogenic
disorders.
PMID- 26432549
TI - Secretion of Na(+), K(+) and fluid by the Malpighian (renal) tubule of the larval
cabbage looper Trichoplusia ni (Lepidoptera: Noctuidae).
AB - The Malpighian (renal) tubules play important roles in ionic and osmotic
homeostasis in insects. In Lepidoptera, the Malpighian tubules are structurally
regionalized and the concentration of Na(+) and K(+) in the secreted fluid varies
depending on the segment of tubule analyzed. In this work, we have characterized
fluid and ion (Na(+), K(+), H(+)) transport by tubules of the larval stage of the
cabbage looper Trichoplusia ni; we have also evaluated the effects of fluid
secretion inhibitors and stimulants on fluid and ion transport. Ramsay assays
showed that fluid was secreted by the iliac plexus but not by the yellow and
white regions of the tubule. K(+) and Na(+) were secreted by the distal iliac
plexus (DIP) and K(+) was reabsorbed in downstream regions. The fluid secretion
rate decreased>50% after 25MUM bafilomycin A1, 500MUM amiloride or 50MUM
bumetanide was added to the bath. The concentration of K(+) in the secreted fluid
did not change, whereas the concentration of Na(+) in the secreted fluid
decreased significantly when tubules were exposed to bafilomycin A1 or amiloride.
Addition of 500MUM cAMP or 1MUM 5-HT to the bath stimulated fluid secretion and
resulted in a decrease in K(+) concentration in the secreted fluid. An increase
in Na(+) concentration in the secreted fluid was observed only in cAMP-stimulated
tubules. Secreted fluid pH and the transepithelial electrical potential (TEP) did
not change when tubules were stimulated. Taken together, our results show that
the secretion of fluid is carried out by the upper regions (DIP) in T. ni
Malpighian tubules. Upper regions of the tubules secrete K(+), whereas lower
regions reabsorb it. Stimulation of fluid secretion is correlated with a decrease
in the K(+)/Na(+) ratio.
PMID- 26432550
TI - Modified technique for transscleral fixation of posterior chamber intraocular
lenses.
AB - BACKGROUND: Suture exposure remains to be a potential problem of transscleral
fixated posterior chamber intraocular lens (PCIOL). We report a modified
technique to minimize the risk of suture exposure for the transscleral fixation
of PCIOL. METHODS: The modified surgical technique is as following: at first, two
3 mm * 4 mm square scleral pockets were created from groove incisions at opposite
positions. A straight needle attached to a 10-0 polypropylene suture was passed
through one incision groove. Then, a 27-Gauge hollow needle passed through the
opposite sclera incision bed was used to retrieve the straight fine needle via
its barrel. The sutures were tied to themselves after one more bite on the
scleral bed. At last, the suture ends were left long (about 4 mm) and laid flat
into corresponding laminar scleral pockets. This modified technique of PCIOL was
performed in 48 post-traumatic aphakic vitrectomized eyes from 48 patients (47
male, one female) with mean age of 34.8 +/- 14.8 years. Main outcome measures
included best corrective visual acuity (BCVA), IOL decentration, IOL tilt, and
postoperative complications. RESULTS: The mean follow-up was 32.3 +/- 10.8 months
(3-67 months). The LogMAR BCVA remained stable, from a preoperative value of 0.46
+/- 0.34 to postoperative 0.44 +/- 0.34 (p = 0.69). Mild IOL tilt (5-10 degrees )
was observed in five eyes, and slight IOL decentration (0.5-1.0 mm) was seen in
three cases. No case of suture exposure, suture breakage, IOL dislocation, or
endophthalmitis was observed during the follow up period. CONCLUSION: The
modified technique allowed stable placement of PCIOLs in post-traumatic aphakic
eyes with a wide range of follow-up. Our procedure might have the potential
benefit to avoid suture exposure in scleral-fixated IOL implantation.
PMID- 26432551
TI - Validation of the Physician Teaching Motivation Questionnaire (PTMQ).
AB - BACKGROUND: Physicians play a major role as teachers in undergraduate medical
education. Studies indicate that different forms and degrees of motivation can
influence work performance in general and that teachers' motivation to teach can
influence students' academic achievements in particular. Therefore, the aim of
this study was to develop and to validate an instrument measuring teaching
motivations in hospital-based physicians. METHODS: We chose self-determination
theory as a theoretical framework for item and scale development. It
distinguishes between different dimensions of motivation depending on the amount
of self-regulation and autonomy involved and its empirical evidence has been
demonstrated in other areas of research. To validate the new instrument (PTMQ =
Physician Teaching Motivation Questionnaire), we used data from a sample of 247
physicians from internal medicine and surgery at six German medical faculties.
Structural equation modelling was conducted to confirm the factorial structure,
correlation analyses and linear regressions were performed to examine concurrent
and incremental validity. RESULTS: Structural equation modelling confirmed a good
global fit for the factorial structure of the final instrument (RMSEA = .050, TLI
= .957, SRMR = .055, CFI = .966). Cronbach's alphas indicated good internal
consistencies for all scales (alpha = .75 - .89) except for the identified
teaching motivation subscale with an acceptable internal consistency (alpha =
.65). Tests of concurrent validity with global work motivation, perceived
teaching competence, perceived teaching involvement and voluntariness of lesson
allocation delivered theory-consistent results with slight deviations for some
scales. Incremental validity over global work motivation in predicting perceived
teaching involvement was also confirmed. CONCLUSIONS: Our results indicate that
the PTMQ is a reliable, valid and therefore suitable instrument for assessing
physicians' teaching motivation.
PMID- 26432553
TI - Synthesis and Fluorescence Properties of Novel indol-3yl-thiazolo[3,2
a][1,3,5]triazines and indole-3-carbaldehyde Schiff Bases.
AB - Novel photoactive 4-(4-chlorophenyl)-2-(1H-indol-3-yl)-6-substituted phenyl-2H
thiazolo[3,2-a][1,3,5]triazines were synthesized by the conjugate addition of
ammonia to the indole-3-carbaldehyde Schiff bases followed by the condensation
with 4-chlorobenzaldehyde. All the synthesized compounds were characterized by FT
IR, NMR, mass spectra and elemental analyses. Their antioxidant property,
electrochemical and photophysical properties in different organic solvents were
investigated. Comparative discussion on the photophysical properties of indole-3
carbaldehyde Schiff bases and 4-(4-chlorophenyl)-2-(1H-indol-3-yl)-6-substituted
phenyl-2H-thiazolo[3,2-a][1,3,5]triazines has been described. The fluorescence
quantum yield of Schiff bases (Phif = 0.66-0.70 in DMSO) found to be
interestingly higher. High fluorescence quantum yield, large molar extinction
coefficient, high stokes shift and smaller optical band gap positioning these new
derivatives as an efficient metal free organic fluorescent and semiconductor
material. Graphical Abstract ?.
PMID- 26432552
TI - Triclosan-coated sutures and sternal wound infections: a prospective randomized
clinical trial.
AB - Surgical site infection is a common complication following cardiac surgery.
Triclosan-coated sutures have been shown to reduce the rate of infections in
various surgical wounds, including wounds after vein harvesting in coronary
artery bypass grafting patients. Our purpose was to compare the rate of
infections in sternotomy wounds closed with triclosan-coated or conventional
sutures. A total of 357 patients that underwent coronary artery bypass grafting
were included in a prospective randomized double-blind single-center study. The
patients were randomized to closure of the sternal wound with either triclosan
coated sutures (Vicryl Plus and Monocryl Plus, Ethicon, Inc., Somerville, NJ,
USA) (n = 179) or identical sutures without triclosan (n = 178). Patients were
followed up after 30 days (clinical visit) and 60 days (telephone interview). The
primary endpoint was the prevalence of sternal wound infection according to the
Centers for Disease Control and Prevention (CDC) criteria. The demographics in
both groups were comparable, including age, gender, body mass index, and rate of
diabetes and smoking. Sternal wound infection was diagnosed in 43 patients; 23
(12.8%) sutured with triclosan-coated sutures compared to 20 (11.2%) sutured
without triclosan (p = 0.640). Most infections were superficial (n = 36, 10.1%),
while 7 (2.0%) were deep sternal wound infections. There were 16 positive
cultures in the triclosan group and 17 in the non-coated suture group (p =
0.842). The most commonly identified main pathogens were Staphylococcus aureus
(45.4%) and coagulase-negative staphylococci (36.4%). Skin closure with triclosan
coated sutures did not reduce the rate of sternal wound infection after coronary
artery bypass grafting. (clinicaltrials.gov: NCT01212315).
PMID- 26432554
TI - Multifunctional theranostic contrast agent for photoacoustics- and ultrasound
based tumor diagnosis and ultrasound-stimulated local tumor therapy.
AB - Biomedical imaging-guided cancer therapy should have capabilities of both
accurate tumor diagnosis and high therapeutic efficacy for the personalized
treatment. Various biomedical imaging-guided cancer therapies are currently being
investigated to overcome current limitations that include low sensitivity of
diagnosis and poor drug delivery to the tumor site. Here, we report the
development of a multifunctional theranostic contrast agent demonstrating high
sensitive photoacoustic and ultrasound imaging and effective local delivery of
anticancer drug to a tumor site. A microbubble (porphyrin-MB) was developed using
phospholipid-porphyrin conjugates to enhance ultrasound and photoacoustic signal
intensities simultaneously. Paclitaxel-loaded human serum albumin nanoparticles
(PTX-HSA-NPs) were then conjugated onto the surface of the microbubble. The
developed PTX-HSA-NPs conjugated porphyrin-MB (porphyrin-MB-NPs) provided
sensitive, dual modal images of a tumor at 700 nm optimal laser wavelength for
photoacoustic imaging and 5-14 MHz operating frequency for the ultrasound
imaging. In addition, porphyrin-MB-NPs efficiently suppressed tumor growth by
ultrasound exposure. Exposure to the focused ultrasound triggered the collapse of
porphyrin-MB-NPs, resulting in the local release of PTX-HSA-NPs and enhanced
penetration into the tumor site. The increased preferential accumulation and
penetration of PTX-HSA-NPs suppressed tumor growth 10-fold more than without
exposure to ultrasound. In conclusion, the developed porphyrin-MB-NPs establish a
new paradigm in simultaneous bi-functional ultrasound/photoacoustic imaging
diagnosis and locally triggered release of nanomedicine and enhanced chemotherapy
efficiency.
PMID- 26432555
TI - Nanoparticulate immunotherapy for cancer.
AB - Although surgery, radiation therapy, and chemotherapy have significantly improved
as treatments for cancer, they can rarely control metastatic disease and cures
remain scarce. Promising recent developments suggest that cancer immunotherapy
may become a powerful new therapy that clinicians can offer cancer patients. The
opportunity to orchestrate the body's own immune system to target, fight, and
eradicate cancer cells without destroying healthy cells makes this an extremely
attractive treatment modality. Our increased knowledge in anti-tumor immunity and
the immunosuppressive tumor microenvironment (TME) has provided many therapeutic
strategies to battle cancer. That combined with advancements in the field of
particulate delivery systems provide a mechanism to deliver these
immunotherapeutics to their specific targeted cells and the TME. In this review
we will focus on the current status of immunotherapy and the potential advantages
of utilizing nanocarriers within the field.
PMID- 26432557
TI - The respiratory chain provides salt stress tolerance by maintaining a low
NADH/NAD+ ratio in Zymomonas mobilis.
AB - The respiratory chain of ethanol-producing Zymomonas mobilis shows an unusual
physiological property in that it is not involved in energy conservation, even
though this organism has a complete electron transport system. We reported
previously that respiratory-deficient mutants (RDMs) of Z. mobilis exhibit higher
growth rates and enhanced ethanol productivity under aerobic and high-temperature
conditions. Here, we demonstrated that the salt tolerance of RDM strains was
drastically decreased compared with the wild-type strain. We found that the
NADH/NAD+ ratio was maintained at low levels in both the wild-type and the RDM
strains under non-stress conditions. However, the ratio substantially increased
in the RDM strains in response to salt stress. Complementation of the deficient
respiratory-chain genes in the RDM strains resulted in a decrease in the
NADH/NAD+ ratio and an increase in the growth rate. In contrast, expression of
malate dehydrogenase, activity of which increases the supply of NADH, in the RDM
strains led to an increased NADH/NAD+ ratio and resulted in poor growth. Taken
together, these results suggest that the respiratory chain of Z. mobilis
functions to maintain a low NADH/NAD+ ratio when the cells are exposed to
environmental stresses, such as salinity.
PMID- 26432556
TI - The Prevention of Hospital Readmissions in Heart Failure.
AB - Heart failure (HF) is a growing healthcare burden and one of the leading causes
of hospitalizations and readmission. Preventing readmissions for HF patients is
an increasing priority for clinicians, researchers, and various stakeholders. The
following review will discuss the interventions found to reduce readmissions for
patients and improve hospital performance on the 30-day readmission process
measure. While evidence-based therapies for HF management have proliferated, the
consistent implementation of these therapies and development of new strategies to
more effectively prevent readmissions remain areas for continued improvement.
PMID- 26432558
TI - Serum-free process development: improving the yield and consistency of human
mesenchymal stromal cell production.
AB - BACKGROUND AIMS: The cost-effective production of human mesenchymal stromal cells
(hMSCs) for off-the-shelf and patient specific therapies will require an
increasing focus on improving product yield and driving manufacturing
consistency. METHODS: Bone marrow-derived hMSCs (BM-hMSCs) from two donors were
expanded for 36 days in monolayer with medium supplemented with either fetal
bovine serum (FBS) or PRIME-XV serum-free medium (SFM). Cells were assessed
throughout culture for proliferation, mean cell diameter, colony-forming
potential, osteogenic potential, gene expression and metabolites. RESULTS:
Expansion of BM-hMSCs in PRIME-XV SFM resulted in a significantly higher growth
rate (P < 0.001) and increased consistency between donors compared with FBS-based
culture. FBS-based culture showed an inter-batch production range of 0.9 and 5
days per dose compared with 0.5 and 0.6 days in SFM for each BM-hMSC donor line.
The consistency between donors was also improved by the use of PRIME-XV SFM, with
a production range of 0.9 days compared with 19.4 days in FBS-based culture. Mean
cell diameter has also been demonstrated as a process metric for BM-hMSC growth
rate and senescence through a correlation (R(2) = 0.8705) across all conditions.
PRIME-XV SFM has also shown increased consistency in BM-hMSC characteristics such
as per cell metabolite utilization, in vitro colony-forming potential and
osteogenic potential despite the higher number of population doublings.
CONCLUSIONS: We have increased the yield and consistency of BM-hMSC expansion
between donors, demonstrating a level of control over the product, which has the
potential to increase the cost-effectiveness and reduce the risk in these
manufacturing processes.
PMID- 26432559
TI - Interferon-gamma and tumor necrosis factor-alpha promote the ability of human
placenta-derived mesenchymal stromal cells to express programmed death ligand-2
and induce the differentiation of CD4(+)interleukin-10(+) and CD8(+)interleukin
10(+)Treg subsets.
AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) and regulatory T cells (Treg)
have been successfully used in treating autoimmune diseases accompanied by
abundant inflammatory cytokines such as interferon (IFN)-gamma and tumor necrosis
factor (TNF)-alpha. Therefore, this work investigated the effects of IFN-gamma
and TNF-alpha on the ability of human placenta-derived mesenchymal stromal cells
(hPMSCs) on inducing the differentiation of CD4(+)interleukin (IL)-10(+)and
CD8(+)IL-10(+)Treg subsets. METHODS: Human PMSCs were co-cultured with T cells in
the presence or absence of a trans-well system or anti- programmed death ligand-2
(PDL2) monoclonal antibody (mAb), respectively. CD4(+)IL-10(+)and CD8(+)IL
10(+)Treg subsets, as well as the levels of IL-10 in the supernatants, were
detected on this basis. Examinations were conducted to explore the impact of IFN
gamma and TNF-alpha on the expression of PDL2 in hPMSCs. In this process, flow
cytometry, Western blot and reverse-transcriptase-polymerase chain reaction were
used. RESULTS: CD4(+)IL-10(+)and CD8(+)IL-10(+)Treg subsets from T cells either
non-activated or activated by use of phytohaemagglutinin (PHA) or CD3/CD28mAb
significantly increased in the presence of hPMSCs. However, these levels markedly
decreased after blocking the expression of PDL2 in hPMSCs. IL-10 followed the
same pattern. Furthermore, the percentages of CD4(+)IL-10(+) and CD8(+)IL-10(+)T
cells also sharply declined under the trans-well system, whereas the percentages
as well as the expression of PDL2 in hPMSCs oppositely raised after hPMSCs pre
stimulated by IFN-gamma and TNF-alpha. IFN-gamma could promote the expression of
PDL2 partly through the JAK/STAT signaling pathway. CONCLUSIONS: IFN-gamma and
TNF-alpha could promote the ability of hPMSCs in inducing the differentiation of
CD4(+)IL-10(+)and CD8(+)IL-10(+)Treg subsets and enhance the expression of PDL2
in hPMSCs. These would benefit the application of hPMSCs in clinical trials.
PMID- 26432560
TI - A novel method to expand large numbers of CD56(+) natural killer cells from a
minute fraction of selectively accessed cryopreserved cord blood for
immunotherapy after transplantation.
AB - BACKGROUND AIMS: Umbilical cord blood transplantation (UCBT) is increasingly used
to treat acute leukemias. UCB units are thawed and infused in their entirety at
transplant, precluding later use as immunotherapy to prevent or treat leukemia
relapse. METHODS: We developed a device that selectively thaws only 1 mL of the
UCB unit, leaving the remaining UCB unit cryopreserved for subsequent
transplantation. We also show that large numbers of CD56(+) natural killer (NK)
cells can be expanded from these 1-mL fractions of selectively accessed UCB.
Immunomagnetic depletion of CD3(+) cells of the 1-mL fraction was performed, and
the cells were subsequently stimulated with irradiated Epstein-Barr virus
transformed lymphoblastoid cell lines (EBV-LCLs) and set to culture in media
containing interleukin (IL)-2. RESULTS: When a 1:20 ratio of total nucleated
cells to EBV-LCL feeder cells was used, day-21 and day-35 NK cell cultures
initiated from 1 mL of UCB contained a median of 430 * 10(6) (range: 44-4321 *
10(6)) and 6092 * 10(6) (range: 165-20947 * 10(6)) CD3(-)CD56(+) NK cells. These
cells expressed high levels of CD161, LFA-1, CD69, NKG2D, NKp30, NKp44, NKp80 and
NKp46. UCB-derived NK cells were highly cytotoxic against K562 leukemia cells,
although cytotoxicity was slightly lower than in expanded PBMC-derived NK cells.
CONCLUSIONS: We have developed and optimized a strategy to selectively access a
small fraction from cryopreserved UCB and show that large numbers of CD56(+)
cells can be expanded from this selectively accessed fraction. This strategy
presents a method to explore whether early adoptive transfer of NK cells expanded
from the same UCB unit used for transplantation can prevent leukemic relapse and
decrease graft-versus-host disease after UCBT.
PMID- 26432561
TI - Biodistribution of in vitro-derived microglia applied intranasally and
intravenously to mice: effects of aging.
AB - BACKGROUND AIMS: The age of both the donor and the recipient has a potential
influence on the efficacy of various cell therapies, but the underlying
mechanisms are still being charted. We studied the effect of donor and recipient
age in the context of microglia migration. METHODS: Microglia were in vitro-
differentiated from bone marrow of young (3 months) and aged (12 months) mice and
transplanted into young (~ 3 months) and aged (~ 17 months) C57BL/6 mice (n = 25)
through intravenous and intranasal application routes. Recipients were not immune
suppressed or irradiated. Transplanted microglia were tracked through the use of
a sex-mismatched setup or histologically with the use of cells from enhanced
green fluorescent protein enhanced green fluorescent protein transgenic mice.
RESULTS: No acute rejections or transplant-associated toxicity was observed.
After 10 days, both intravenously and intranasally transplanted cells were
detected in the brain. Transplanted cells were also found in the blood and the
lymph system. The applied cells were also tracked in lungs and kidney but only
after intravenous injection subjected to a "pulmonary first-pass effect." After
28 days, intravenously delivered cells were also found in the bone marrow and
other organs, especially in aged recipients. Whereas in young recipients the
transplanted microglia did not appear to persist, in aged brains the transplanted
cells could still be identified up to 28 days after transplantation. However,
when cells from aged donors were used, no signals of transplanted cells could be
detected in the recipients. CONCLUSIONS: This study establishes proof of
principle that in vitro--derived microglia from young but not from aged donors,
intravenously or intranasally transplanted, migrate to the brain in young and
aged recipients.
PMID- 26432562
TI - A Case of Recurrent Ischemic Stroke Involving Subacute, Progressive Intracranial
Cerebral Arterial Sclerosis Prior to Diagnosis with JAK2-mutated Polycythemia
Vera.
AB - CASE REPORT: A 58-year-old man presenting with no vascular risk factors visited
our hospital with right hemiparesis and total aphasia. Diffusion-weighted
magnetic resonance imaging of the brain showed multiple hyperintensities in
watershed distributions in the left hemisphere. Magnetic resonance angiography
(MRA) revealed stenosis of the middle cerebral artery, despite normal MRA
findings 2 months prior. One year after the first stroke, the patient experienced
a recurrent ischemic stroke involving the left anterior choroidal artery,
pulmonary embolism, and deep venous thrombosis. After the recurrent stroke event,
hemoglobin levels increased gradually. Two years after the first stroke, a JAK2V
617F mutation was detected. CONCLUSION: Our report suggests that progressive
intracranial arterial sclerosis and venous thrombosis of undetermined etiologies
could be several initial symptoms of polycythemia vera.
PMID- 26432563
TI - Regional Gray Matter Atrophy in Vascular Mild Cognitive Impairment.
AB - BACKGROUND: The aim of this study was to explore the neuroanatomical bases of
vascular mild cognitive impairment (VaMCI) with respect to attention/executive
function, memory, language, and visuospatial function. METHODS: We used voxel
based morphometric analysis to identify brain regions that significantly differed
in terms of gray matter volumes (GMVs) between 43 patients with VaMCI and 55
healthy controls. Then, we compared the individual GMVs of the selected regions
with the neuropsychological profiles of the VaMCI patients. RESULTS: The delayed
recall component of the Rey-Osterrieth Complex Figure Test (CFT) (74.4%), the
Symbol Digit Modalities Test (74.4%), the Boston Naming Test (51.2%), and the CFT
copy (81.4%) shared the highest incidence of impairment in the 4 cognitive
domains, respectively. Compared with controls, patients with VaMCI exhibited
significantly reduced GMVs. This effect was mainly present in the frontal
regions, including the bilateral dorsolateral prefrontal cortex (DLPFC), the
orbital portion of the superior frontal gyrus (SFG), and the left supplemental
motor area, and was also observed in the bilateral posterior cingulated cortex
(PCC). GMVs were significantly correlated with performance in the Trail Making
Test, part B, in the bilateral DLPFC and PCC, the clock drawing test in the right
orbital portion of the SFG, and CFT-delayed recall in the right PCC. CONCLUSIONS:
These results, from the perspective of brain morphology, uniquely explored the
specific cerebral structural changes of VaMCI, thus providing a deeper
understanding of the pathophysiology of the disease.
PMID- 26432564
TI - Actinoplanes rhizophilus sp. nov., an actinomycete isolated from the rhizosphere
of Sansevieria trifasciata Prain.
AB - A novel actinomycete, designated strain NEAU-A-2T, was isolated from the
rhizosphere soil of Sansevieria trifasciata Prain collected from Heilongjiang
province, north-east China. The taxonomic status of this organism was established
using a polyphasic approach. The isolate formed irregular sporangia containing
motile spores on the substrate mycelium. The whole-cell sugars were xylose and
galactose. The predominant menaquinones were MK-9(H10), MK-9(H2), MK-10(H2) and
MK-10(H4). The major fatty acids were iso-C15 : 0, iso-C16 : 0 and anteiso-C15 :
0. The polar lipids were diphosphatidylglycerol,
phosphatidylmonomethylethanolamine, phosphatidylethanolamine,
phosphatidylinositol, three unidentified phospholipids and an unidentified
glycolipid. 16S rRNA gene sequence similarity studies showed that strain NEAU-A
2T belongs to the genus Actinoplanes with the highest sequence similarities to
Actinoplanes globisporus NBRC 13912T (97.7 % 16S rRNA gene sequence similarity),
Actinoplanes ferrugineus IMSNU 22125T (97.5 %), Actinoplanes toevensis MN07
A0368T (97.2 %) and Actinoplanes rishiriensis NBRC 108556T (97.2 %); similarities
to type strains of other species of this genus were < 97 %. Two tree-making
algorithms showed that strain NEAU-A-2T formed a distinct clade with A.
globisporus NBRC 13912T and A. rishiriensis NBRC 108556T. However, low DNA-DNA
relatedness values allowed the isolate to be differentiated from the above
mentioned two species of the genus Actinoplanes. Moreover, strain NEAU-A-2T could
also be distinguished from the most closely related species by morphological and
physiological characteristics. Therefore, in conclusion, isolate NEAU-A-2T
represents a novel species of the genus Actinoplanes, for which the name
Actinoplanes rhizophilus sp. nov. is proposed. The type strain is NEAU-A-2T ( =
CGMCC 4.7133T = DSM 46672T).
PMID- 26432565
TI - Trifocal Intraocular Lens Implantation to Treat Visual Demands in Various
Distances Following Lens Removal.
AB - PURPOSE: To evaluate visual and refractive outcomes after implantation of a
trifocal intraocular lens (IOL). DESIGN: Prospective, nonrandomized
noncomparative case series. METHODS: setting: Department of Ophthalmology, Goethe
University, Frankfurt/Germany. patient or study population: Twenty-seven patients
(54 eyes) who had bilateral implantation of the AT LISA trifocal IOL (AT LISA
tri839MP; Carl Zeiss Meditec, Jena, Germany) pre-enrollment. Exclusion criteria
were previous ocular surgeries excluding cataract surgery and refractive lens
exchange, irregular corneal astigmatism of >1.5 diopter, and ocular pathologies
or corneal abnormalities. Intervention or Observation Procedure(s): Postoperative
examination at 1 and 3 months included manifest refraction; monocular and
binocular uncorrected (UCVA) and distance-corrected (DCVA) visual acuity in 4 m,
80 cm, and 40 cm; slit-lamp examination; and tomography. At 3 months defocus
testing, binocular contrast sensitivity (CS) under photopic and mesopic
conditions, and a questionnaire on subjective quality of vision, optical
phenomena, and spectacle independence were performed. MAIN OUTCOME MEASURE(S):
Three-months-postoperative monocular and binocular UCVA and DCVA in 4 m, 80 cm,
and 40 cm (logMAR); defocus curve; CS; and quality-of-vision questionnaire
results. RESULTS: Mean spherical equivalent was 0.05 +/- 0.32 D 3 months
postoperatively. Binocular UCVA at distance, intermediate, and near was -0.1 +/-
0.1 logMAR, 0.0 +/- 0.1 logMAR, and 0.0 +/- 0.1 logMAR, respectively. Despite
some optical phenomena, 92% of patients would choose the same IOL again.
CONCLUSION: Evaluation of a trifocal IOL showed good VA (0.1 logMAR or better) at
far, intermediate, and near distance; high patient satisfaction despite some
optical phenomena; and high spectacle independence 3 months postoperatively.
PMID- 26432566
TI - How Big Data Informs Us About Cataract Surgery: The LXXII Edward Jackson Memorial
Lecture.
AB - PURPOSE: To characterize the role of Big Data in evaluating quality of care in
ophthalmology, to highlight opportunities for studying quality improvement using
data available in the American Academy of Ophthalmology Intelligent Research in
Sight (IRIS) Registry, and to show how Big Data informs us about rare events such
as endophthalmitis after cataract surgery. DESIGN: Review of published studies,
analysis of public-use Medicare claims files from 2010 to 2013, and analysis of
IRIS Registry from 2013 to 2014. METHODS: Statistical analysis of observational
data. RESULTS: The overall rate of endophthalmitis after cataract surgery was
0.14% in 216 703 individuals in the Medicare database. In the IRIS Registry the
endophthalmitis rate after cataract surgery was 0.08% among 511 182 individuals.
Endophthalmitis rates tended to be higher in eyes with combined cataract surgery
and anterior vitrectomy (P = .051), although only 0.08% of eyes had this combined
procedure. Visual acuity (VA) in the IRIS Registry in eyes with and without
postoperative endophthalmitis measured 1-7 days postoperatively were logMAR 0.58
(standard deviation [SD]: 0.84) (approximately Snellen acuity of 20/80) and
logMAR 0.31 (SD: 0.34) (approximately Snellen acuity of 20/40), respectively. In
33 547 eyes with postoperative VA after cataract surgery, 18.3% had 1-month
postoperative VA worse than 20/40. CONCLUSIONS: Big Data drawing on Medicare
claims and IRIS Registry records can help identify additional areas for quality
improvement, such as in the 18.3% of eyes in the IRIS Registry having 1-month
postoperative VA worse than 20/40. The ability to track patient outcomes in Big
Data sets provides opportunities for further research on rare complications such
as postoperative endophthalmitis and outcomes from uncommon procedures such as
cataract surgery combined with anterior vitrectomy. But privacy and data-security
concerns associated with Big Data should not be taken lightly.
PMID- 26432567
TI - Corneal Deformation Response and Ocular Geometry: A Noninvasive Diagnostic
Strategy in Marfan Syndrome.
AB - PURPOSE: To evaluate corneal air-puff deformation responses and ocular geometry
as predictors of Marfan syndrome. DESIGN: Prospective observational clinical
study. METHODS: Sixteen investigator-derived, 4 standard Ocular Response Analyzer
(ORA), and geometric variables from corneal tomography and optical biometry using
Oculus Pentacam and IOL Master were assessed for discriminative value in Marfan
syndrome, measuring right eyes of 24 control and 13 Marfan syndrome subjects.
Area under the receiver operating characteristic (AUROC) curve was assessed in
univariate and multivariate analyses. RESULTS: Six investigator-derived ORA
variables successfully discriminated Marfan syndrome. The best lone disease
predictor was Concavity Min (Marfan syndrome 47.5 +/- 20, control 69 +/- 14, P =
.003; AUROC = 0.80). Corneal hysteresis (CH) and corneal resistance factor (CRF)
were decreased (Marfan syndrome CH 9.45 +/- 1.62, control CH 11.24 +/- 1.21, P =
.01; Marfan syndrome CRF 9.77 +/- 1.65, control CRF 11.03 +/- 1.72, P = .01) and
corneas were flatter in Marfan syndrome (Marfan syndrome Kmean 41.25 +/- 2.09
diopter, control Kmean 42.70 +/- 1.81 diopter, P = .046). No significant
differences were observed in central corneal thickness, axial eye length, or
intraocular pressure. A multivariate regression model incorporating corneal
curvature and hysteresis loop area (HLA) provided the best predictive value for
Marfan syndrome (AUROC = 0.85). CONCLUSIONS: This study describes novel
biodynamic features of corneal deformation responses in Marfan syndrome,
including increased deformation, decreased bending resistance, and decreased
energy dissipation capacity. A predictive model incorporating HLA and corneal
curvature shows greatest potential for noninvasive clinical diagnosis of Marfan
syndrome.
PMID- 26432568
TI - Effect of Serial Intrasilicone Oil Bevacizumab Injections in Eyes With Recurrent
Proliferative Vitreoretinopathy Retinal Detachment.
AB - PURPOSE: To investigate the effect of serial intrasilicone oil bevacizumab
injections (1.25 mg/0.05 mL) on visual acuity (VA) and anatomic outcomes in eyes
undergoing proliferative vitreoretinopathy (PVR)-related retinal detachment (RD)
repair. DESIGN: Prospective, nonrandomized, historical-control pilot study.
METHODS: setting: Tertiary care center. STUDY POPULATION: Nondiabetic eyes
undergoing pars plana vitrectomy (PPV) and silicone oil tamponade with or without
scleral buckling procedure (SBP) for recurrent RD due to PVR. INTERVENTION:
Intrasilicone oil injection of 1.25 mg bevacizumab was performed intraoperatively
and at postoperative months 1, 2, and 3. OUTCOMES: Retinal reattachment rate,
final VA, and rate of epiretinal membrane (ERM) formation at month 6. RESULTS:
Twenty eyes of 20 patients were enrolled and compared to a historical control
group composed of 35 age- and sex-matched controls. In the study group, logMAR VA
improved from mean 1.78 +/- 0.43 (Snellen 20/1205) to 1.43 +/- 0.70 (Snellen
20/538, P = .04), retinal reattachment was achieved in 14 of 20 eyes (70%), and
ERM formation was observed in 7 of 20 eyes (35%) at 6 months. In the control
group, logMAR VA improved from mean 1.50 +/- 0.74 (Snellen 20/632) to 1.43 +/-
0.58 (Snellen 20/538, P = .64), retinal reattachment was achieved in 25 of 35
eyes (71%), and ERM formation was observed in 7 of 35 eyes (20%) at 6 months. No
significant difference in final VA (P = .96), retinal reattachment rate (P =
.75), or ERM formation (P = .33) was observed between groups. No intrasilicone
oil injection-related adverse events occurred. CONCLUSIONS: Serial intrasilicone
oil injections of bevacizumab did not improve retinal reattachment rate, improve
final VA, or reduce ERM formation in patients undergoing PVR-related RD surgery.
PMID- 26432569
TI - Secretory IgA from submucosal glands does not compensate for its airway surface
deficiency in chronic obstructive pulmonary disease.
AB - Secretory immunoglobulin A (SIgA) reaches the airway lumen by local transcytosis
across airway epithelial cells or with tracheobronchial submucosal gland
secretions. In chronic obstructive pulmonary disease (COPD), deficiency of SIgA
on the airway surface has been reported. However, reduction of SIgA levels in
sputum and bronchoalveolar lavage (BAL) fluid has not been consistently observed.
To explain this discrepancy, we analyzed BAL fluid and lung tissue from patients
with COPD and control subjects. Immunohistochemical analysis of large and small
airways of COPD patients showed that MUC5AC is the predominant mucin expressed by
airway epithelial cells, whereas MUC5B is expressed in submucosal glands of large
airways. Dual immunostaining with anti-IgA and anti-MUC5B antibodies showed
reduction of IgA on the airway surface as well as accumulation of IgA within
MUC5B-positive luminal mucus plugs, suggesting that luminal SIgA originates from
submucosal glands in COPD patients. We found that the concentration of SIgA in
BAL is inversely correlated with forced expiratory volume in 1 s (FEV1) in COPD,
but that the ratio of SIgA/MUC5B is a better predictor of FEV1, particularly in
patients with moderate COPD. Together, these findings suggest that SIgA
production by submucosal glands, which are expanded in COPD, is insufficient to
compensate for reduced SIgA transcytosis by airway epithelial cells. Localized
SIgA deficiency on the surface of small airways is associated with COPD
progression and represents a potential new therapeutic target in COPD.
PMID- 26432570
TI - Epidemiological investigation of caries prevalence in first grade school children
in Rhineland-Palatinate, Germany.
AB - INTRODUCTION: The annual examination of first graders' oral health as stipulated
by law aimed to reach every child in Rhineland-Palatinate (Germany) in their
first year of school. We intended to evaluate the first graders' oral health
based on the examination data for 2013/2014. METHODS: Instructed examiners
measured the d3mft(deciduous)/D3MFT(permanent) index according to World Health
Organization criteria in 25,020 predominantly 6-7 year-old first-grade school
children. Only caries affecting dentin was diagnosed; no radiography or fiber
transillumination was used. Out of the d3mft value, the "Significant Caries
Index" (SiC) was calculated. This index identifies the dmft score of the third of
the population with the highest caries experience. Descriptive analysis was
performed. RESULTS: Out of the the examined children, 60.9% were caries free.
Mean d3mft score was 1.28 +/- 2.27 while the mean SiC was 3.73 +/- 2.51. A
distinctly higher d3mft was found in the decidous molars compared to the front
teeth. Boys were significantly more caries-experienced than girls (p < 0.001).
CONCLUSION: The results of this study confirm the lasting trend towards
decreasing caries prevalence in children starting school found in previous cross
sectional studies. This trend was observed in the high-risk group (obtained by
SiC) as well as in the entire study population. Particular attention in caries
prophylaxis should be paid to the primary molars.
PMID- 26432571
TI - The Burden of Polypharmacy in Patients Near the End of Life.
AB - CONTEXT: Patients with advanced illness are prescribed multiple medications in
the last year of life, intensifying the risk of negative consequences related to
polypharmacy. OBJECTIVES: To describe the medication burden of patients near the
end of life and identify potential areas for improvement in clinician prescribing
practices. METHODS: This was a prespecified secondary analysis of data from a
prospective trial. Eligible participants were adults with less than 12 months
estimated prognosis taking a statin medication for primary prevention of
cardiovascular disease. Participants were enrolled from 15 sites, randomized to
continue or discontinue statin medications, and followed for up to a year.
Concomitant medications were recorded at least monthly from study enrollment
through death. Prescribed medications were categorized by class and subclass.
Descriptive statistics were calculated. RESULTS: On average, participants (n =
244) were 74.3 years old (SD 11.5) and lived 264 days (SD 128); 47.5% of the
patients had a primary diagnosis of malignant tumor. This population was exposed
to medications across 51 classes, 192 subclasses, and 423 individual medications.
Patients took an average of 11.5 (SD 5) medications at the time of enrollment and
10.7 (SD 5) medications at death or study termination. The five most common
classes of medications prescribed near the end of life were antihypertensives,
broncholytics/bronchodilators, laxatives, antidepressants, and gastric protection
agents. CONCLUSION: There is a significant medication burden placed on patients
with advanced illness. Although most medications were prescribed for supportive
care, we observed a high prevalence of medications for managing non-life
threatening comorbidities.
PMID- 26432572
TI - Rifampin (INN Rifampicin).
AB - Therapeutic Reviews aim to provide essential independent information for health
professionals about drugs used in palliative and hospice care. Additional content
is available on www.palliativedrugs.com. Country-specific books (Hospice and
Palliative Care Formulary USA, and Palliative Care Formulary, British and
Canadian editions) are also available and can be ordered from
www.palliativedrugs.com. The series editors welcome feedback on the articles
(hq@palliativedrugs.com).
PMID- 26432573
TI - Chronic Aerobic Exercise Decreases Lectin-Like Low Density Lipoprotein (LOX-1)
Receptor Expression in Heart of Diabetic Rat.
AB - BACKGROUND: Overexpression of lectin-like low density lipoprotein (LOX-1)
receptor plays an important role in hyperglycemia-induced vascular complications
such as atherosclerosis. Based on the beneficial effects of exercise on
preventing cardiovascular complications of diabetes, we aimed to examine the
protective effects of aerobic exercise on expression of LOX-1 receptor and
production of free radicals in the heart of diabetic rats. METHODS: Four groups
of rats were used: (n = 5 per group): sedentary normal, trained normal, sedentary
diabetes and trained diabetes. Diabetes was induced by a single intraperitoneal
injection of streptozotocin (50 mg/kg). The exercise protocol was consisted of
swimming 30 min/day, 5 days/week for eight weeks. Plasma glucose was evaluated at
initiation, weeks 4 and 8 of experiment. At the end of experiment, rats were
sacrificed and the heart was removed for determination of nitrate,
malondialdehyde, and LOX-1 gene expression. RESULTS: In normal non-diabetic rats,
the blood glucose level was <150 mg/dl; however, the induction of diabetes
resulted in levels more than >400 mg/dl. Gene expression of LOX-1 was increased
in the heart of diabetic rats. Exercise reduced the gene expression of this
protein in diabetic states without reducing the blood glucose. Finally, swimming
exercise decreased the malondialdehyde and nitrate levels in heart tissue both in
control and diabetic rats. CONCLUSION: Swimming exercise reduces heart expression
of the LOX-1 receptor in accompany with reduction of free radicals production.
Since these parameters are important in generation of diabetic complications,
swimming exercise is a good candidate for reducing these complications.
PMID- 26432574
TI - The impact of hypoxia on mesenchymal progenitor cells of human skeletal tissue in
the pathogenesis of heterotopic ossification.
AB - PURPOSE: Mesenchymal progenitor cells (MPCs) are capable of differentiating into
osteo/chondrogenic cells to contribute substantially to heterotopic ossification
(HO). This study aimed to examine the impact of hypoxia on MPCs in the aetiology
of HO. METHODS: MPCs from human normal and HO skeletal tissue were cultivated
under normoxia and hypoxia. Gene expression of factors which have a key role in
HO aetiology (BMPs, COX-1 and COX-2, etc.) were examined by real-time PCR. Tissue
of both groups was analysed by immunohistochemistry. RESULTS: Under hypoxia, COX
1, -2 and SOX-9 gene expression was elevated in HO MPCs, whereas in normal muscle
tissue only COX-2 was upregulated. MPCs from HO had a significantly elevated gene
expression of BMP-4 and decreased expression of BMP-1 and HIF-1 under hypoxia
compared to normal MPCs. Immunohistochemistry detected no significant differences
between normal and HO tissue. CONCLUSIONS: Hypoxia causes an enhanced gene
expression of factors, which have a key role in HO pathophysiology. A better
understanding of this entity will possibly allow reducing HO rates in orthopaedic
and trauma surgery.
PMID- 26432576
TI - Ectopic germinoma involving multiple midline and paramedian structures outside
the pineal gland or hypophyseal region of the brain prior to tumor development.
PMID- 26432575
TI - Biomechanical evaluation of different surgical techniques for treating patellar
tendon ruptures.
AB - PURPOSE: The aim of this study was to biomechanically assess patellar tendon
repair techniques with additional cable wire or polydioxanone suture (PDS) cord
augmentation in comparison with a suture-anchor repair technique. METHODS:
Patellar tendon repair was performed in 60 specimens using a porcine bone model.
Yield load, maximum load, stiffness and elongation of patellar tendon
reconstructions with (1) cable wire augmentation, (2) PDS cord augmentation or
(3) suture anchor repair were evaluated using a cyclic loading and load-to
failure test setup. RESULTS: In comparison with suture anchor repair,
augmentation of the reconstruction with either cable wires or PDS cords provides
significantly higher maximum loads (527 and 460 N vs. 301 N; p < 0.01 and p =
0,012, respectively) under load-to-failure testing and less elongation (8.81 mm
+/- 1.55 mm and 10.56 mm +/- 3.1 mm vs. 18.38 mm +/- 7.51 mm; p = 0.037 and p =
0.033, respectively) under cyclic loading conditions. CONCLUSION: Augmentation of
a patellar tendon repair with either a cable wire or a PDS cord provides higher
primary stability than suture anchor repair in patellar tendon ruptures. The
study supports the use of additional augmentation of a tendon repair in the
clinical setting in order to prevent loss of reduction and allow for early post
operative mobilisation.
PMID- 26432577
TI - Quantitative muscle ultrasound measures rapid declines over time in children with
SMA type 1.
AB - Muscles are small in spinal muscular atrophy (SMA). It is not known if muscle
size changes over time in SMA type 1. We quantified changes over time in muscle
size and echointensity during two repeated ultrasound examinations of unilateral
proximal (biceps brachii/brachialis and quadriceps) and distal (anterior forearm
flexors and tibialis anterior) muscles in three children with SMA type 1. We
compared muscle thickness (MT) to body weight-dependent normal reference values.
Children were 1, 6, and 11months old at baseline and had 2, 2 and 4 months
between ultrasound examinations, respectively. At baseline, MT was normal for
weight in all muscles except an atrophic quadriceps in the oldest child. MT
decreased and echointensity increased (worsened) over time. At follow up, MT was
below normal for weight in the quadriceps in all three children, in the
biceps/brachioradialis in two, and in the anterior forearm in one. Tibialis
anterior MT remained normal for weight in all three children. Muscle
echointensity increased over time in all muscles and, on average, more than
doubled in two children. In children with SMA type 1, muscle atrophies and
becomes hyperechoic over time. Quantitative muscle ultrasound measures disease
progression in SMA type 1 that warrants additional study in more children.
PMID- 26432578
TI - Recurrent cerebral infarction synchronous with menorrhagia caused by endometrial
stromal sarcoma.
PMID- 26432579
TI - Petroleomics by Direct Analysis in Real Time-Mass Spectrometry.
AB - The analysis of crude oil and its fractions by applying ambient ionization
techniques remains underexplored in mass spectrometry (MS). Direct analysis in
real time (DART) in the positive-ion mode was coupled to a linear quadrupole ion
trap Orbitrap mass spectrometer (LTQ Orbitrap) to analyze crude oil, paraffin
samples, and porphyrin standard compounds. The ionization parameters of DART-MS
were optimized for crude oil analysis. DART-MS rendered the optimum conditions of
the operation using paper as the substrate, T = 400 degrees C, helium as the
carrier gas, and a sample concentration >=6 mg mL(-1). In the crude oils
analysis, the DART(+)-Orbitrap mass spectra detected the typical N, NO, and O
containing compounds. In the paraffin samples, oxidized hydrocarbon species (Ox
classes, where x = 1-4) with double-bond equivalent of 1-4 were detected, and
their structures and connectivity were confirmed by collision-induced
dissociation (CID) experiments. DART(+)-MS has identified the porphyrin standard
compounds as [M + H](+) ions of m/z 615.2502 and 680.1763, where M = C44H30N4 and
C44H28N4OV, respectively, based on the formula assignment and by phenyl losses
observed on CID experiments.
PMID- 26432580
TI - Mechanistic Study on Electronic Excitation Dissociation of the Cellobiose-Na(+)
Complex.
AB - The recent development of electron activated dissociation (ExD) techniques has
opened the door for high-throughput, detailed glycan structural elucidation.
Among them, ExD methods employing higher-energy electrons offer several
advantages over low-energy electron capture dissociation (ECD), owing to their
applicability towards chromophore-labeled glycans and singly charged ions, and
ability to provide more extensive structural information. However, a lack of
understanding of these processes has hindered rational optimization of the
experimental conditions for more efficient fragmentation as well as the
development of informatics tools for interpretation of the complex glycan ExD
spectra. Here, cellobiose-Na(+) was used as the model system to investigate the
fragmentation behavior of metal-adducted glycans under irradiation of electrons
with energy exceeding their ionization potential, and served as the basis on
which a novel electronic excitation dissociation (EED) mechanism was proposed. It
was found that ionization of the glycan produces a mixture of radical cations and
ring-opened distonic ions. These distonic ions then capture a low-energy electron
to produce diradicals with trivial singlet-triplet splitting, and subsequently
undergo radical-induced dissociation to produce a variety of fragment ions, the
abundances of which are influenced by the stability of the distonic ions from
which they originate. Graphical Abstract ?.
PMID- 26432582
TI - Bipolar voltage amplitude: What does it really mean?
PMID- 26432581
TI - Enhanced cardiac device management utilizing the random EGM: A neglected feature
of remote monitoring.
PMID- 26432583
TI - Elderly man with ICD shocks.
PMID- 26432584
TI - Nadolol decreases the incidence and severity of ventricular arrhythmias during
exercise stress testing compared with beta1-selective beta-blockers in patients
with catecholaminergic polymorphic ventricular tachycardia.
AB - BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an
inheritable cardiac disease predisposing to malignant ventricular arrhythmias.
OBJECTIVE: We aimed to explore the incidence and severity of ventricular
arrhythmias in patients with CPVT before the initiation of beta-blocker
treatment, when treated with beta1-selective beta-blockers, and when treated with
nadolol. METHODS: In this study, 34 patients with CPVT were included (mean age 34
+/- 19 years; 15 (44%) women; 30 (88%) ryanodine receptor 2 variant positive). We
performed 3 bicycle exercise stress tests in each patient: (1) before the
initiation of beta-blocker treatment, (2) after >6 weeks of treatment with beta1
selective beta-blockers and (3) after >6 weeks of treatment with nadolol. We
recorded resting and maximum heart rates and the most severe ventricular
arrhythmia occurring. Severity of arrhythmias was scored as 1 point for no
arrhythmias or only single ventricular extrasystoles, 2 points for >10
ventricular extrasystoles per minute or bigeminy, 3 points for couplets, and 4
points for nonsustained ventricular tachycardia or sustained ventricular
tachycardia. RESULTS: Resting heart rate was similar during treatment with
nadolol and beta1-selective beta-blockers (54 +/- 10 beats/min vs 56 +/- 14
beats/min; P = .50), while maximum heart rate was lower during treatment with
nadolol compared with beta1-selective beta-blockers (122 +/- 21 beats/min vs 139
+/- 24 beats/min; P = .001). Arrhythmias during exercise stress testing were less
severe during treatment with nadolol compared with during treatment with beta1
selective beta-blockers (arrhythmic score 1.6 +/- 0.9 vs 2.5 +/- 0.8; P < .001)
and before the initiation of beta-blocker treatment (arrhythmic score 1.6 +/- 0.9
vs 2.7 +/- 0.9; P = .001); however, no differences were observed during treatment
with beta1-selective beta-blockers compared with before the initiation of beta
blocker treatment (arrhythmic score 2.5 +/- 0.8 vs 2.7 +/- 0.9; P = .46).
CONCLUSION: The incidence and severity of ventricular arrhythmias decreased
during treatment with nadolol compared with during treatment with beta1-selective
beta-blockers. beta1-Selective beta-blockers did not change the occurrence or
severity of arrhythmias compared with no medication.
PMID- 26432585
TI - Right-to-left frequency gradient during atrial fibrillation initiated by right
atrial ectopies and its augmentation by adenosine triphosphate: Implications of
right atrial fibrillation.
AB - BACKGROUND: A left-to-right dominant frequency (DF) gradient commonly exists in
paroxysmal atrial fibrillation (AF). AF initiated by right atrial (RA) ectopy (AF
RAE) is rare. OBJECTIVE: This study aimed to investigate characteristics of AF
RAE using pharmacological maneuvers and spectral analysis. METHODS: Seventy-nine
consecutive patients referred for catheter ablation of paroxysmal AF were
enrolled. Infusions of isoproterenol and adenosine triphosphate (ATP) were used
to induce AF. Patients with AF-RAE and patients with AF initiated only by
pulmonary vein (PV) ectopies were classified into the RA-ectopy group (n = 7[9%])
and PV-ectopy group (n = 32[41%]), respectively. ATP was also injected during
ongoing AF to unmask the driver of AF. High RA, coronary sinus, and PV-left
atrial junction electrograms and electrocardiogram lead V1 underwent spectral
analyses. RESULTS: Patients in the RA-ectopy group were younger (51 +/- 13 years
vs 63 +/- 7 years; P = .01) and more commonly had a family history of AF (71% vs
9%; P < .001) than patients in the PV-ectopy group. There was a baseline right-to
left DF gradient in the RA-ectopy group (PV-left atrial junction: 6.0 +/- 0.4 Hz;
coronary sinus: 5.7 +/- 0.6 Hz; RA: 7.3 +/- 0.8 Hz; P < .05) in contrast to a
left-to-right DF gradient in the PV-ectopy group (5.9 +/- 0.8, 5.3 +/- 0.7, 5.2
+/- 0.8 Hz; P < .01). ATP injection predominantly increased the DF of the high RA
in the RA-ectopy group and augmented a right-to-left DF gradient (7.9 +/- 1.8,
7.6 +/- 1.0, 10.7 +/- 0.7 Hz; P < .001), whereas it augmented a left-to-right DF
gradient in the PV-ectopy group (7.9 +/- 1.0, 6.4 +/- 0.5, 6.6 +/- 1.2 Hz; P <
.05). CONCLUSION: A rare type of paroxysmal AF initiated by RA ectopy may be
maintained by a reentrant driver localized in the RA (so-called RA fibrillation).
PMID- 26432586
TI - From the desk of the Editor-in-Chief.
PMID- 26432587
TI - Space radiation protection: Destination Mars.
AB - National space agencies are planning a human mission to Mars in the XXI century.
Space radiation is generally acknowledged as a potential showstopper for this
mission for two reasons: a) high uncertainty on the risk of radiation-induced
morbidity, and b) lack of simple countermeasures to reduce the exposure. The need
for radiation exposure mitigation tools in a mission to Mars is supported by the
recent measurements of the radiation field on the Mars Science Laboratory.
Shielding is the simplest physical countermeasure, but the current materials
provide poor reduction of the dose deposited by high-energy cosmic rays.
Accelerator-based tests of new materials can be used to assess additional
protection in the spacecraft. Active shielding is very promising, but as yet not
applicable in practical cases. Several studies are developing technologies based
on superconducting magnetic fields in space. Reducing the transit time to Mars is
arguably the best solution but novel nuclear thermal-electric propulsion systems
also seem to be far from practical realization. It is likely that the first
mission to Mars will employ a combination of these options to reduce radiation
exposure.
PMID- 26432588
TI - Changes in miRNA expression profile of space-flown Caenorhabditis elegans during
Shenzhou-8 mission.
AB - Recent advances in the field of molecular biology have demonstrated that small
non-coding microRNAs (miRNAs) have a broad effect on gene expression networks and
play a key role in biological responses to environmental stressors. However,
little is known about how space radiation exposure and altered gravity affect
miRNA expression. The "International Space Biological Experiments" project was
carried out in November 2011 by an international collaboration between China and
Germany during the Shenzhou-8 (SZ-8) mission. To study the effects of spaceflight
on Caenorhabditis elegans (C. elegans), we explored the expression profile miRNA
changes in space-flown C. elegans. Dauer C. elegans larvae were taken by SZ-8
spacecraft and experienced the 16.5-day shuttle spaceflight. We performed miRNA
microarray analysis, and the results showed that 23 miRNAs were altered in a
complex space environment and different expression patterns were observed in the
space synthetic and radiation environments. Most putative target genes of the
altered miRNAs in the space synthetic environment were predicted to be involved
in developmental processes instead of in the regulation of transcription, and the
enrichment of these genes was due to space radiation. Furthermore, integration
analysis of the miRNA and mRNA expression profiles confirmed that twelve genes
were differently regulated by seven miRNAs. These genes may be involved in
embryonic development, reproduction, transcription factor activity, oviposition
in a space synthetic environment, positive regulation of growth and body
morphogenesis in a space radiation environment. Specifically, we found that cel
miR-52, -55, and -56 of the miR-51 family were sensitive to space environmental
stressors and could regulate biological behavioural responses and neprilysin
activity through the different isoforms of T01C4.1 and F18A12.8. These findings
suggest that C. elegans responded to spaceflight by altering the expression of
miRNAs and some target genes that function in diverse regulatory pathways.
PMID- 26432589
TI - Differential effects of p53 on bystander phenotypes induced by gamma ray and high
LET heavy ion radiation.
AB - High LET particle irradiation has several potential advantages over gamma-rays
such as p53-independent response. The purpose of this work is to disclose the
effect of p53 on the bystander effect induced by different LET irradiations and
underlying mechanism. Lymphocyte cells of TK6 (wild type p53) and HMy2.CIR
(mutated p53) were exposed to either low or high LET irradiation, then their
mitochondrial dysfunction and ROS generation were detected. The micronuclei (MN)
induction in HL-7702 hepatocytes co-cultured with irradiated lymphocytes was also
measured. It was found that the mitochondrial dysfunction, p66(Shc) activation,
and intracellular ROS were enhanced in TK6 but not in HMy2.CIR cells after gamma
ray irradiation, but all of them were increased in both cell lines after carbon
and iron irradiation. Consistently, the bystander effect of MN formation in HL
7702 cells was only triggered by gamma-irradiated TK6 cells but not by gamma
irradiated HMy2.CIR cells. But this bystander effect was induced by both
lymphocyte cell lines after heavy ion irradiation. PFT-MU, an inhibitor of p53,
only partly inhibited ROS generation and bystander effect induced by 30 keV/MUm
carbon-irradiated TK6 cells but failed to suppress the bystander effect induced
by the TK6 cells irradiated with either 70 keV/MUm carbon or 180 keV/MUm iron.
The mitochondrial inhibitors of rotenone and oligomycin eliminated heavy ion
induced ROS generation in TK6 and HMy2.CIR cells and hence diminished the
bystander effect on HL-7702 cells. These results clearly demonstrate that the
bystander effect is p53-dependent for low LET irradiation, but it is p53
independent for high LET irradiation which may be because of p53-independent ROS
generation due to mitochondrial dysfunction.
PMID- 26432590
TI - The evaluation of upper body muscle activity during the performance of external
chest compressions in simulated hypogravity.
AB - BACKGROUND: This original study evaluated the electromyograph (EMG) activity of
four upper body muscles: triceps brachii, erector spinae, upper rectus abdominis,
and pectoralis major, while external chest compressions (ECCs) were performed in
simulated Martian hypogravity using a Body Suspension Device, counterweight
system, and standard full body cardiopulmonary resuscitation (CPR) mannequin.
METHOD: 20 young, healthy male subjects were recruited. One hundred compressions
divided into four sets, with roughly six seconds between each set to indicate
'ventilation', were performed within approximately a 1.5 minute protocol. Chest
compression rate, depth and number were measured along with the subject's heart
rate (HR) and rating of perceived exertion (RPE). RESULTS: All mean values were
used in two-tailed t-tests using SPSS to compare +1 Gz values (control) versus
simulated hypogravity values. The AHA (2005) compression standards were
maintained in hypogravity. RPE and HR increased by 32% (p<0.001) and 44%
(p=0.002), respectively, when ECCs were performed during Mars simulation, in
comparison to +1 Gz. In hypogravity, the triceps brachii showed significantly
less activity (p<0.001) when compared with the other three muscles studied. The
comparison of all the other muscles showed no difference at +1 Gz or in
hypogravity. CONCLUSIONS: This study was among the first of its kind, however
several limitations were faced which hopefully will not exist in future studies.
Evaluation of a great number of muscles will allow space crews to focus on
specific strengthening exercises within their current training regimes in case of
a serious cardiac event in hypogravity.
PMID- 26432591
TI - Inhibition of microRNA-31-5p protects human colonic epithelial cells against
ionizing radiation.
AB - MicroRNAs (miRNAs), endogenous non-coding small RNAs, are sensitive to
environmental changes, and their differential expression is important for
adaptation to the environment. However, application of miRNAs as a clinical
prognostic or diagnostic tool remains unproven. In this study we demonstrate a
chronic/persistent change of miRNAs from the plasma of a colorectal cancer
susceptible mouse model (CPC;Apc) about 250 days after exposure to a simulated
solar particle event (SPE). Differentially expressed miRNAs were identified
compared to unirradiated control mice, including miR-31-5p, which we investigated
further. To address the cellular function of miR-31-5p, we transfected a miR-31
5p mimic (sense) or inhibitor (antisense) into immortalized human colonic
epithelial cells followed by gamma-irradiation. A miR-31-5p mimic sensitized but
a miR-31-5p inhibitor protected colonic epithelial cells against radiation
induced killing. We found that the miR-31-5p mimic inhibited the induction of
hMLH1 expression after irradiation, whereas the miR-31-5p inhibitor increased the
basal level of hMLH1 expression. The miR-31-5p inhibitor failed to modulate
radiosensitivity in an hMLH1-deficient HCT116 colon cancer cell line but
protected HCT116 3-6 and DLD-1 (both hMLH1-positive) colon cancer cell lines. Our
findings demonstrate that miR-31-5p has an important role in radiation responses
through regulation of hMLH1 expression. Targeting this pathway could be a
promising therapeutic strategy for future personalized anti-cancer radiotherapy.
PMID- 26432592
TI - Comparison of space flight and heavy ion radiation induced genomic/epigenomic
mutations in rice (Oryza sativa).
AB - Rice seeds, after space flight and low dose heavy ion radiation treatment were
cultured on ground. Leaves of the mature plants were obtained for examination of
genomic/epigenomic mutations by using amplified fragment length polymorphism
(AFLP) and methylation sensitive amplification polymorphism (MSAP) method,
respectively. The mutation sites were identified by fragment recovery and
sequencing. The heritability of the mutations was detected in the next
generation. Results showed that both space flight and low dose heavy ion
radiation can induce significant alterations on rice genome and epigenome
(P<0.05). For both genetic and epigenetic assays, while there was no significant
difference in mutation rates and their ability to be inherited to the next
generation, the site of mutations differed between the space flight and radiation
treated groups. More than 50% of the mutation sites were shared by two radiation
treated groups, radiated with different LET value and dose, while only about 20%
of the mutation sites were shared by space flight group and radiation treated
group. Moreover, in space flight group, we found that DNA methylation changes
were more prone to occur on CNG sequence than CG sequence. Sequencing results
proved that both space flight and heavy ion radiation induced mutations were
widely spread on rice genome including coding region and repeated region. Our
study described and compared the characters of space flight and low dose heavy
ion radiation induced genomic/epigenomic mutations. Our data revealed the
mechanisms of application of space environment for mutagenesis and crop breeding.
Furthermore, this work implicated that the nature of mutations induced under
space flight conditions may involve factors beyond ion radiation.
PMID- 26432593
TI - Biological filter capable of simultaneous nitrification and denitrification for
Aquatic Habitat in International Space Station.
AB - The biological filter capable of simultaneous nitrification and denitrification
was constructed for aquatic animal experiments in the International Space Station
(ISS). The biological filter will be used to remove harmful ammonia excreted from
aquatic animals in a closed water circulation system (Aquatic Habitat). The
biological filter is a cylindrical tank packed with porous glass beads for
nitrification and dual plastic bags for denitrification. The porous beads are
supporting media for Nitrosomonas europaea and Nitrobacter winogradskyi. The N.
europaea cells and N. winogradskyi cells on the porous beads, oxidize the
excreted ammonia to nitrate via nitrite. On the other hand, the dual bag is
composed of an outer non-woven fabric bag and an inner non-porous polyethylene
film bag. The outer bag is supporting media for Paracoccus pantotrophus. The
inner bag, in which 99.5% ethanol is packed, releases the ethanol slowly, since
ethanol can permeate through the non-porous polyethylene film. The P.
pantotrophus cells on the outer bag reduce the produced nitrate to nitrogen gas
by using the released ethanol as an electron donor for denitrification. The
biological filter constructed in this study consequently removed the ammonia
without accumulating nitrate. Most of the excess ethanol was consumed and did not
affect the nitrification activity of the N. europaea cells and N. winogradskyi
cells severely. In accordance with the aquatic animal experiments in the ISS,
small freshwater fish had been bred in the closed water circulation system
equipped with the biological filter for 90 days. Ammonia concentration daily
excreted from fish is assumed to be 1.7 mg-N/L in the recirculation water. Under
such conditions, the harmful ammonia and nitrite concentrations were kept below
0.1 mg-N/L in the recirculation water. Nitrate and total organic carbon
concentrations in the recirculation water were kept below 5 mg-N/L and 3 mg-C/L,
respectively. All breeding fish were alive and ate the feed well. The results
show that the nitrification and denitrification abilities of the biological
filter sufficed to keep water quality for aquatic animal experiments in the ISS.
This simple and effective system is certainly applicable to aquarium systems and
aquaculture systems.
PMID- 26432594
TI - Quality factors for space radiation: A new approach.
AB - NASA has derived new models for radiological risk assessment based on
epidemiological data and radiation biology including differences in Relative
Biological Effectiveness for leukemia and solid tumors. Comprehensive approaches
were used to develop new risk cross sections and the extension of these into
recommendations for risk assessment during space missions. The methodology relies
on published data generated and the extensive research initiative managed by the
NASA Human Research Program (HRP) and reviewed by the National Academy of
Sciences. This resulted in recommendations for revised specifications of quality
factors, QNASA(Z,beta) in terms of track structure concepts that extend beyond
LET alone. The new paradigm for quality factors placed demands on radiation
monitoring procedures that are not satisfied by existing dosimetry systems or
particle spectrometers that are practical for space exploration where mass,
volume, band width and power consumption are highly constrained. We have proposed
a new definition of quality factors that relaxes the requirements for identifying
charge, Z, and velocity, beta, of the incident radiation while still preserving
the functional form of the inherent risk functions. The departure from the exact
description of QNASA(Z,beta) is that the revised values are new functions of LET
for solid cancers and leukemia. We present the motivation and process for
developing the revised quality factors. We describe results of extensive
simulations using GCR distributions in free space as well as the resulting
spectra of primary and secondary particles behind aluminum shields and
penetration through water. In all cases the revised dose averaged quality factors
agreed with those based on the values obtained using QNASA(Z,beta). This provides
confidence that emerging technologies for space radiation dosimetry can provide
real time measurements of dose and dose equivalent while satisfying constraints
on size, mass, power and bandwidth. The revised quality factors are sufficiently
generalized to be applicable to radiation protection practices beyond space
exploration.
PMID- 26432595
TI - Chlorpromazine transformation by exposure to ultraviolet laser beams in droplet
and bulk.
AB - Multiple drug resistance requires a flexible approach to find medicines able to
overcome it. One method could be the exposure of existing medicines to
ultraviolet laser beams to generate photoproducts that are efficient against
bacteria and/or malignant tumors. This can be done in droplets or bulk volumes.
In the present work are reported results about the interaction of 266nm and 355nm
pulsed laser radiation with microdroplets and bulk containing solutions of
10mg/ml Chlorpromazine Hydrochloride (CPZ) in ultrapure water. The irradiation
effects on CPZ solution at larger time intervals (more than 30min) are similar in
terms of generated photoproducts if the two ultraviolet wavelengths are utilized.
The understanding of the CPZ parent compound transformation may be better
evidenced, as shown in this paper, if studies at shorter than 30minute exposure
times are made coupled with properly chosen volumes to irradiate. We show that at
exposure to a 355nm laser beam faster molecular modifications of CPZ in ultrapure
water solution are produced than at irradiation with 266nm, for both microdroplet
and bulk volume samples. These effects are evidenced by thin layer chromatography
technique and laser induced fluorescence measurements.
PMID- 26432596
TI - Histological features of oral epithelium in seven animal species: As a reference
for selecting animal models.
AB - Several animals have been used as models for basic and clinical research on oral
mucosa. Few studies have focused on the selection of an appropriate animal model.
This study aimed to provide histological references for selecting a potential
model. Histological features were assessed by exploring 6 morphological
characteristics and 2 immunohistochemical markers. The morphological
characteristics included keratinization, basal membrane appearance, epithelial
thickness, rete ridge length, adjacent rete ridge distance, and regional
variation; the immunohistochemical markers included Ki67 (a proliferative marker)
and Cytokeratin 19 (CK19; a stemness marker). The histological similarity of each
species compared to humans was calculated according to the designated scoring
criteria. The results showed that the buccal mucosae from dog and pig were non
keratinized, with similar rete ridge length and distance, compared to that of
humans. The dog, rat, and cavy mucosae had analogous gross appearances in the
basal membrane. The dog oral mucosae shared similar epithelial thickness with
human oral mucosae. Compared to the human mucosa, the dog, pig, rat, and rabbit
mucosae exhibited corresponding regional variations. The Ki67-positive cells in
human and canine mucosae were predominantly localized in the suprabasal layers,
whereas most of the proliferative cells were in the basal layer in other species.
CK19 immunoreactivities were detected only in human and canine mucosae. The
canine mucosae gained the highest point value (14), whereas the scores for the
pig, rat, rabbit, cavy, sheep, and buffalo mucosae were 8, 6, 5, 5, 5, and 2,
respectively. The histological variations in the oral epithelium of diverse
animal species are considerable; the mucosae from dogs are most similar to human
mucosae, implicating its histological basis as an animal model.
PMID- 26432599
TI - Characteristic sign of a colonic submucosal lesion.
PMID- 26432597
TI - Targeting downstream transcription factors and epigenetic modifications following
Toll-like receptor 7/8 ligation to forestall tissue injury in anti-Ro60
associated heart block.
AB - Based on the consistent demonstration of fibrosis of the atrioventricular node
surrounded by macrophages and multinucleated giant cells in anti-Ro antibody
exposed fetuses dying with heart block, this study focuses on macrophage
signaling stimulated by ssRNA associated with the Ro60 protein and the impact of
antagonizing innate cell drivers such as TLR7/8. Transcriptome and epigenetic
modifications which affect transcription factors, NF-kappaB and STAT1, were
selected to evaluate the phenotype of macrophages in which TLR7/8 was ligated
following treatment with either anti-Ro60/Ro60/hY3 RNA immune complexes or
transfection with hY3. Based on microarray, TNF and IL6 were among the most
highly upregulated genes in both stimulated conditions, each of which was
significantly inhibited by preincubation with hydroxychloroquine (HCQ). In
contrast, following stimulation of macrophages with either TNF-alpha or IFN
alpha, which do not signal through TLR, the resultant gene expression was
refractory to HCQ. Ligation of TLR7/8 resulted in increased histone methylation
as measured by increased H3K4me2, a requirement for binding of NF-kappaB at
certain promoters, specifically the kB1 region in the TNF promoter (ChIP-qPCR),
which was significantly decreased by HCQ. In summary, these results support that
the HCQ-sensitive phenotype of hY3 stimulated macrophages reflects the
bifurcation of TLR downstream signals involving NF-kappaB and STAT 1 pathways and
for the former dimethylation of H3K4. Accordingly, HCQ may act more as a
preventive measure in downregulating the initial production of IFN-alpha or TNF
alpha and not affect the resultant autocoid stimulation reflected in TNF-alpha
and IFN-alpha responsive genes. The beneficial scope of antimalarials in the
prevention of organ damage, inclusive of heart block in an anti-Ro offspring or
more broadly SLE, may include in part, a mechanism targeting TLR-dependent
epigenetic modification.
PMID- 26432598
TI - Successful treatment of murine autoimmune cholangitis by parabiosis: Implications
for hematopoietic therapy.
AB - There is a significant unmet need in the treatment of primary biliary cirrhosis
(PBC) despite significant data on the effector pathways that lead to biliary duct
damage. We focused attention on a murine model of PBC, the dominant negative
transforming growth factor beta receptor II (Tg) mice. To further define the
pathways that lead to biliary pathology in these mice, we developed Tg mice
deleted of CD4 cells (CD4(-/-)Tg). Interestingly, these mice developed more
severe cholangitis than control Tg mice. These mice, which lack CD4 cells,
manifested increased levels of IFN-gamma produced by effector CD8 cells. It
appears that increased cholangitis is due to the absence of CD4 Treg cells. Based
on these data, we parabiosed CD4(-/-)Tg mice with established disease at 8-9
weeks of age with C57BL/6 control mice. Such parabiotic "twins" had a significant
reduction in autoimmune cholangitis, even though they had established pathology
at the time of surgery. We prepared mixed bone marrow chimera mice constructed
from CD4(-/-)Tg and CD8(-/-) mice and not only was cholangitis improved, but a
decrease in terminally differentiated CD8(+) T effector cells in the presence of
wild type CD4 cells was noted. In conclusion, "correcting" the CD4 T cell subset,
even in the presence of pathogenic CD8 T cells, is effective in treating
autoimmune cholangitis.
PMID- 26432600
TI - MicroRNA expression and protein acetylation pattern in respiratory and limb
muscles of Parp-1(-/-) and Parp-2(-/-) mice with lung cancer cachexia.
AB - BACKGROUND: Current treatment options for cachexia, which impairs disease
prognosis, are limited. Muscle-enriched microRNAs and protein acetylation are
involved in muscle wasting including lung cancer (LC) cachexia. Poly(ADP-ribose)
polymerases (PARP) are involved in muscle metabolism. We hypothesized that muscle
enriched microRNA, protein hyperacetylation, and expression levels of myogenic
transcription factors (MTFs) and downstream targets, muscle loss and function
improve in LC cachectic Parp-1(-/-) and Parp-2(-/-) mice. METHODS: Body and
muscle weights, grip strength, muscle phenotype, muscle-enriched microRNAs (miR
1, -133, -206, and -486), protein acetylation, acetylated levels of FoxO1, FoxO3,
and PGC-1alpha, histone deacetylases (HDACs) including SIRT1, MTFs, and
downstream targets (alpha-actin, PGC-1alpha, and creatine kinase) were evaluated
in diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) wild type (WT), Parp
1(-/-) and Parp-2-/- mice. RESULTS: Compared to WT cachectic animals, in both
respiratory and limb muscles of Parp-1(-/-) and Parp-2(-/-) cachectic mice:
downregulation of muscle-specific microRNAs was counterbalanced especially in
gastrocnemius of Parp-1(-/-) mice; increased protein acetylation was attenuated
(improvement in HDAC3, SIRT-1, and acetylated FoxO3 levels in both muscles,
acetylated FoxO1 levels in the diaphragm); reduced MTFs and creatine kinase
levels were mitigated; body and muscle weights, strength, and muscle fiber sizes
improved, while tumor weight and growth decreased. CONCLUSIONS: These molecular
findings may explain the improvements seen in body and muscle weights, limb
muscle force and fiber sizes in both Parp-1(-/-) and Parp-2(-/-) cachectic mice.
GENERAL SIGNIFICANCE: PARP-1 and -2 play a role in cancer-induced cachexia, thus
selective pharmacological inhibition of PARP-1 and -2 may be of interest in
clinical settings.
PMID- 26432601
TI - Production of 4-hydroxybutyrate from succinate semialdehyde in butyrate
biosynthesis in Porphyromonas gingivalis.
AB - BACKGROUND: Despite evidence demonstrating the importance of butyrate-producing
bacteria in host health and disease, the characterization of enzymes responsible
for butyrate production has not been fully elucidated in the periodontopathogen,
Porphyromonas gingivalis. METHODS: LC-MS/MS and colorimetric analyses were
employed to enzymatically characterize recombinant PGN_0724 in P. gingivalis as a
succinate semialdehyde reductase. The concentration of short chain fatty acids in
the culture supernatant of the wild-type bacteria and a mutant strain lacking the
PGN_0724 gene were quantified using GC-MS. RESULTS: Incubation of recombinant
PGN_0724 with succinate semialdehyde and NADH resulted in the production of 4
hydroxybutyrate as well as consumption of succinate semialdehyde. Double
reciprocal plots showed that the reaction catalyzed by the PGN_0724 protein was
associated with a ternary complex mechanism. The growth speed and final turbidity
of the mutant strain were much lower than those of the wild-type cells. The
capacity of the mutant strain to produce butyrate, isobutyrate, and isovalerate
was 30%, 15%, and 45%, respectively, of that of the wild-type strain, while the
mutant strain produced approximately 3.9-fold more propionate than the wild type.
CONCLUSIONS: The pathway responsible for butyrate production is important for the
growth of P. gingivalis and appears to be associated with production of the other
short chain fatty acids. GENERAL SIGNIFICANCE: The aim of this study was to
delineate the mechanisms involved in the production of 4-hydroxybutyrate, which
is an intermediate in the biosynthetic pathway for production of butyrate, which
is a virulence factor in P. gingivalis.
PMID- 26432602
TI - Microbial diversity and dynamics throughout manufacturing and ripening of surface
ripened semi-hard Danish Danbo cheeses investigated by culture-independent
techniques.
AB - Microbial successions on the surface and in the interior of surface ripened semi
hard Danish Danbo cheeses were investigated by culture-dependent and -independent
techniques. Culture-independent detection of microorganisms was obtained by
denaturing gradient gel electrophoresis (DGGE) and pyrosequencing, using
amplicons of 16S and 26S rRNA genes for prokaryotes and eukaryotes, respectively.
With minor exceptions, the results from the culture-independent analyses
correlated to the culture-dependent plating results. Even though the predominant
microorganisms detected with the two culture-independent techniques correlated, a
higher number of genera were detected by pyrosequencing compared to DGGE.
Additionally, minor parts of the microbiota, i.e. comprising <10.0% of the
operational taxonomic units (OTUs), were detected by pyrosequencing, resulting in
more detailed information on the microbial succession. As expected, microbial
profiles of the surface and the interior of the cheeses diverged. During cheese
production pyrosequencing determined Lactococcus as the dominating genus on
cheese surfaces, representing on average 94.7%+/-2.1% of the OTUs. At day 6
Lactococcus spp. declined to 10.0% of the OTUs, whereas Staphylococcus spp. went
from 0.0% during cheese production to 75.5% of the OTUs at smearing. During
ripening, i.e. from 4 to 18 weeks, Corynebacterium was the dominant genus on the
cheese surface (55.1%+/-9.8% of the OTUs), with Staphylococcus (17.9%+/-11.2% of
the OTUs) and Brevibacterium (10.4%+/-8.3% of the OTUs) being the second and
third most abundant genera. Other detected bacterial genera included
Clostridiisalibacter (5.0%+/-4.0% of the OTUs), as well as Pseudoclavibacter,
Alkalibacterium and Marinilactibacillus, which represented <2% of the OTUs. At
smearing, yeast counts were low with Debaryomyces being the dominant genus
accounting for 46.5% of the OTUs. During ripening the yeast counts increased
significantly with Debaryomyces being the predominant genus, on average
accounting for 96.7%+/-4.1% of the OTUs. The interior of the cheeses was
dominated by Lactococcus spp. comprising on average 93.9%+/-7.8% of the OTUs
throughout the cheese processing. The microbial dynamics described at genus level
in this study add to a comprehensive understanding of the complex microbiota
existing especially on surface ripened semi-hard cheeses.
PMID- 26432603
TI - Design, synthesis and structure-activity relationship of novel diphenylamine
derivatives.
AB - Diphenylamine derivatives have been reported with good fungicidal, insecticidal,
acaricidal, rodenticidal and/or herbicidal activities. To find new lead compound
of this kind, a series of novel diphenylamine derivatives were designed and
synthesized by the approach of Intermediate Derivatization Methods. All compounds
were identified by (1)H NMR and elemental analysis. Bioassays demonstrated that
some compounds substituted at 2,4,6-positions or 2,4,5-positions of phenyl ring B
exhibited excellent fungicidal activities. The optimal compounds P30 and P33
showed 80% and 85% control respectively against cucumber downy mildew at 12.5mgL(
1), both 100% control against rice blast at 0.3mgL(-1) and both 100% control
against cucumber gray mold at 0.9mgL(-1). The relationship between structure and
fungicidal activities was discussed as well.
PMID- 26432604
TI - Evaluation of small molecule SecA inhibitors against methicillin-resistant
Staphylococcus aureus.
AB - Due to the emergence and rapid spread of drug resistance in bacteria, there is an
urgent need for the development of novel antimicrobials. SecA, a key component of
the general bacterial secretion system required for viability and virulence, is
an attractive antimicrobial target. Earlier we reported that systematical
dissection of a SecA inhibitor, Rose Bengal (RB), led to the development of novel
small molecule SecA inhibitors active against Escherichia coli and Bacillus
subtilis. In this study, two potent RB analogs were further evaluated for
activities against methicillin-resistant Staphylococcus aureus (MRSA) strains and
for their mechanism of actions. These analogs showed inhibition on the ATPase
activities of S. aureus SecA1 (SaSecA1) and SecA2 (SaSecA2), and inhibition of
SaSecA1-dependent protein-conducting channel. Moreover, these inhibitors reduce
the secretion of three toxins from S. aureus and exert potent bacteriostatic
effects against three MRSA strains. Our best inhibitor SCA-50 showed potent
concentration-dependent bactericidal activity against MRSA Mu50 strain and very
importantly, 2-60 fold more potent inhibitory effect on MRSA Mu50 than all the
commonly used antibiotics including vancomycin, which is considered the last
resort option in treating MRSA-related infections. Protein pull down experiments
further confirmed SaSecA1 as a target. Deletion or overexpression of NorA and
MepA efflux pumps had minimal effect on the antimicrobial activities against S.
aureus, indicating that the effects of SecA inhibitors were not affected by the
presence of these efflux pumps. Our studies show that these small molecule
analogs target SecA functions, have potent antimicrobial activities, reduce the
secretion of toxins, and have the ability to overcome the effect efflux pumps,
which are responsible for multi-drug resistance. Thus, targeting SecA is an
attractive antimicrobial strategy against MRSA.
PMID- 26432605
TI - 5-Lipoxygenase inhibitors suppress RANKL-induced osteoclast formation via NFATc1
expression.
AB - 5-Lipoxygenase synthesizes leukotrienes from arachidonic acid. We developed three
novel 5-LO inhibitors having a benzoxazole scaffold as a potential anti
osteoclastogenics. They significantly suppressed RANKL-induced osteoclast
formation in mouse bone marrow-derived macrophages. Furthermore, one compound,
K7, inhibited the bone resorptive activity of osteoclasts. The anti
osteoclastogenic effect of K7 was mainly attributable to reduction in the
expression of NFATc1, an essential transcription factor for osteoclast
differentiation. K7 inhibited osteoclast formation via ERK and p38 MAPK, as well
as NF-kappaB signaling pathways. K7 reduced lipopolysaccharide (LPS)-induced
osteoclast formation in vivo, corroborating the in vitro data. Thus, K7 exerted
an inhibitory effect on osteoclast formation in vitro and in vivo, properties
that make it a potential candidate for the treatment of bone diseases associated
with excessive bone resorption.
PMID- 26432606
TI - Design, synthesis and insecticidal evaluation of aryloxy dihalopropene
derivatives.
AB - Plutella xylostella (P. xylostella) is a highly migratory, cosmopolitan species
and one of the most important pest of cruciferous crops worldwide. Pyridalyl as a
novel class of insecticides has good efficacy against P. xylostella. On the basis
of the commercial insecticide pyridalyl, a series of new aryloxy dihalopropene
derivatives were designed and synthesized by using Intermediate Derivatization
Methods. Their chemical structures were confirmed by (1)H NMR, high-resolution
mass spectrum (HRMS), and single-crystal X-ray diffraction analysis. The
insecticidal activities of the new compounds against P. xylostella were
evaluated. The results of bioassays indicated that most of the compounds showed
moderate to high activities at the tested concentration, especially compounds 10e
and 10g displayed more than 75% insecticidal activity against P. xylostella at
6.25mg/L, while pyridalyl showed 50% insecticidal activity at the same
concentration. The field trials result of the insecticidal activities showed that
compound 10e as a 10% emulsifiable concentrate (EC) was effective in the control
of P. xylostella at 75-150g a.i./ha, and the mortality of P. xylostella for
treatment with compound 10e at 75g a.i./ha was equivalent to pyridalyl at 105g
a.i./ha.
PMID- 26432607
TI - Click-tailed coumarins with potent and selective inhibitory action against the
tumor-associated carbonic anhydrases IX and XII.
AB - Coumarins behave as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC
4.2.1.1) with a mechanism of inhibition distinct from other classes of
inhibitors. A series of 7-substituted coumarins incorporating aryl-triazole
moieties were prepared by click chemistry procedures starting from 7
hydroxycoumarin or 4-methyl-7-aminocoumarin. The panel of new compounds was
assayed for the inhibition of the cytosolic, widespread human (h) isoforms hCA I
and II, and the transmembrane, tumor-associated ones hCA IX and XII. Most of the
coumarins were weak inhibitors or did not inhibit significantly hCA I and II, but
showed low nanomolar inhibitory action against the transmembrane isoforms (K(I)
of 14.3-34.4 nM against hCA IX and of 4.7-37.8 nM against hCA XII). Since many
hypoxic tumors overexpress hCA IX/XII, and as these targets were recently
validated for obtaining antitumor/antimetastatic agents, with one inhibitor in
Phase I clinical trials, the present findings constitute an interesting extension
to the knowledge of non-sulfonamide, selective inhibitors of CA isoforms involved
in serious pathologies.
PMID- 26432608
TI - Development of novel dipeptide-like rhodesain inhibitors containing the 3
bromoisoxazoline warhead in a constrained conformation.
AB - Novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline
warhead in a constrained conformation were developed; some of them possess K(i)
values in the micromolar range. We studied the structure-activity relationship of
these derivatives and we performed docking studies, which allowed us to find out
the key interactions established by the inhibitors with the target enzyme.
Biological results indicate that the nature of the P2 and P3 substituents and
their binding to the S2/S3 pockets is strictly interdependent.
PMID- 26432609
TI - Antimicrobial and cytotoxic activities of 1,2,3-triazole-sucrose derivatives.
AB - A library of 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-1,2,3
triazoles have been investigated for their antibacterial, antifungal and
cytotoxic activities. Most of the target compounds showed good inhibitory
activity against a variety of clinically and food contaminant important microbial
pathogens. In particular, 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'
yl)-4-(4-pentylphenyl)-1,2,3-triazole (5) was highly active against all the
tested bacteria with minimal inhibitory concentrations (MICs) ranging between 1.1
and 4.4 uM and bactericidal concentrations (MBCs) from 2.2 and 8.4 uM. The
compound 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-(4
bromophenyl)-1,2,3-triazole (3) showed antifungal activity with MICs from 0.6 to
4.8 uM and minimal fungicidal concentrations (MFCs) ranging between 1.2 and 8.9
uM. Furthermore, some of the compounds possessed moderate cytotoxicity against
human breast, lung, cervical and hepatocellular carcinoma cell lines, without
showing toxicity for non-tumor liver cells. The above mentioned derivatives
represent promising leads for the development of new generation of sugar-triazole
antifungal agents.
PMID- 26432610
TI - Ab initio studies on the structure of and atomic interactions in cellulose III(I)
crystals.
AB - The crystal structure of cellulose III(I)was analyzed using first-principles
density functional theory (DFT). The geometry was optimized using variable-cell
relaxation, as implemented in Quantum ESPRESSO. The Perdew-Burke-Ernzerhof (PBE)
functional with a correction term for long-range van der Waals interactions (PBE
D) reproduced the experimental structure well. By using the optimized crystal
structure, the interactions existed among the cellulose chains in the crystal
were precisely investigated using the NBO analysis. The results showed that the
weak bonding nature of CH/O and the hydrogen bonding occur among glucose
molecules in the optimized crystal structure. To investigate the strength of
interaction, dimeric and trimeric glucose units were extracted from the crystal,
and analyzed using MP2 ab initio counterpoise methods with BSSE correction. The
results estimated the strength of the interactions. That is, the packed chains
along with a-axis interacts with weak bonding nature of CH/O and dispersion
interactions by -7.50 kcal/mol, and two hydrogen bonds of O2HO2...O6 and
O6HO6...O2 connect the neighboring packed chains with -11.9 kcal/mol. Moreover,
FMO4 calculation was also applied to the optimized crystal structure to estimate
the strength of the interactions. These methods can well estimate the
interactions existed in the crystal structure of cellulose III(I).
PMID- 26432611
TI - Synthesis of glycosyl fluorides from (phenylthio)glycosides using IF5-pyridine
HF.
AB - IF5-pyridine-HF, an air- and moisture-stable fluorinating reagent, was applied to
the synthesis of glycosyl fluorides from (phenylthio)glycosides. Common
protecting groups of alcohol and diol can tolerate the reaction conditions
performed, and therefore, the present method is applicable to the synthesis of
various glycosyl fluorides.
PMID- 26432612
TI - Structures of three different neutral polysaccharides of Acinetobacter baumannii,
NIPH190, NIPH201, and NIPH615, assigned to K30, K45, and K48 capsule types,
respectively, based on capsule biosynthesis gene clusters.
AB - Neutral capsular polysaccharides (CPSs) were isolated from Acinetobacter
baumannii NIPH190, NIPH201, and NIPH615. The CPSs were found to contain common
monosaccharides only and to be branched with a side-chain 1->3-linked beta-d
glucopyranose residue. Structures of the oligosaccharide repeat units (K units)
of the CPSs were elucidated by 1D and 2D (1)H and (13)C NMR spectroscopy. Novel
CPS biosynthesis gene clusters, designated KL30, KL45, and KL48, were found at
the K locus in the genome sequences of NIPH190, NIPH201, and NIPH615,
respectively. The genetic content of each gene cluster correlated with the
structure of the CPS unit established, and therefore, the capsular types of the
strains studied were designated as K30, K45, and K48, respectively. The
initiating sugar of each K unit was predicted, and glycosyltransferases encoded
by each gene cluster were assigned to the formation of the linkages between
sugars in the corresponding K unit.
PMID- 26432613
TI - Biochemical and Histological Effects of Thiamine Pyrophosphate against
Acetaminophen-Induced Hepatotoxicity.
AB - The aim of this study was to investigate whether thiamine pyrophosphate (TPP) has
biochemical and histological preventive effects on oxidative liver damage induced
by paracetamol (APAP). Rats were divided into the following groups: healthy
control (HG), APAP (AG, 1500 mg/kg, orally), thiamine pyrophosphate (TPPG, 100
mg/kg, intraperitoneally), APAP+NAC (ANAC, 100 mg/kg, intraperitoneally),
APAP+TPP (ATPG) and APAP+NAC+TPP (ANTG). Oxidant, antioxidant parameters, liver
function tests and histological assessment were performed between groups.
Malondialdehyde levels in the AG, HG, TPPG, ANAC, ATPG and ANTG groups were 0.470
+/- 0.210, 0.213 +/- 0.004, 0.194 +/- 0.001, 0.197 +/- 0.06, 0.199 +/- 0.008 and
0.173 +/- 0.010 MUmol/g protein, respectively. Total glutathione levels were
7.787 +/- 0.395, 14.925 +/- 0.932, 13.200 +/- 0.984, 13.162 +/- 0.486, 13.287 +/-
0.787 and 13.500 +/- 0.891 MUm/g protein, respectively. In the AG group, marked
liver damage occurred with the elevation of liver function tests and oxidative
stress markers, such as malondialdehyde, myeloperoxidase and nitric oxide (p <
0.05). Biochemical results were congruent with the histological changes of
oxidative damage. Compared to the AG group (p < 0.05), TPP significantly reduced
oxidant parameter levels in the ATPG group and simultaneously increased the
antioxidant parameter levels of catalase and glutathione. The histological
changes were improved to almost normal hepatic structure. Moreover, TPP had
nearly the same hepatoprotective effect as NAC, and there was statistically no
additional benefit with NAC co-treatment. There was no statistically significant
difference (p > 0.05) among the ANAC, ANTG and ATPG groups in terms of
oxidant/antioxidant levels. TPP proved to be as efficacious as standard therapy
and may be beneficial in APAP-induced hepatotoxicity.
PMID- 26432614
TI - Synthesis, in vitro evaluation and molecular docking studies of biscoumarin
thiourea as a new inhibitor of alpha-glucosidases.
AB - Biscoumarin analogs 1-18 have been synthesized, characterized by EI-MS and (1)H
NMR and evaluated for alpha-glucosidase inhibitory potential. All compounds
showed variety of alpha-glucosidase inhibitory potential ranging in between
13.5+/-0.39 and 104.62+/-0.3MUM when compared with standard acarbose having IC50
value 774.5+/-1.94MUM. The binding interactions of the most active analogs were
confirmed through molecular docking. The compounds showed very good interactions
with enzyme. All synthesized compounds 1-18 are new. Our synthesized compounds
can further be studied to developed lead compounds.
PMID- 26432615
TI - Synthesis, characterization, anti-inflammatory and anti-proliferative activity
against MCF-7 cells of O-alkyl and O-acyl flavonoid derivatives.
AB - A series of O-alkyl and O-acyl flavonoid derivatives was synthesized in high
efficiency. Alkylation and acylation of 5-hydroxyflavonoids showed that the low
reactivity hydroxyl group, 5-OH, well reacted with strong reagents whereas with
weaker reagents, the different products were obtained dependently on structural
characteristic of ring C of respective flavonoid. In order to evaluate anti
inflammatory activity, all compounds were tested for in vitro inhibition of
bovine serum albumin denaturation and in vivo inhibition of carrageenan-induced
mouse paw edema. Among them, the compounds 3, 3b, 4b and 4c demonstrated more
effective anti-inflammatory activity than standard drugs (diclofenac sodium and
ketoprofen) in both tests. Meanwhile, the flavonoids 2, 2c, 3a and 4b displayed
anti-proliferative activity against MCF-7 cell lines. Triacetyl derivative of
hesperetin 4b inducing degradation of DNA in MCF-7 cells was observed.
PMID- 26432616
TI - Research and development of bronchodilators for asthma and COPD with a focus on G
protein/KCa channel linkage and beta2-adrenergic intrinsic efficacy.
AB - Bronchodilators are used to improve symptoms and lung function in asthma and
COPD. Airway smooth muscle tone is regulated by both muscarinic and beta2
adrenergic receptor activity. Large-conductance Ca(2+)-activated K(+) (KCa)
channels are activated by beta2-adrenergic receptor agonists, via Gs, and
suppressed by muscarinic receptor antagonists via Gi. This functional antagonism
converges on the G protein/KCa channel linkages. Membrane potential regulated by
KCa channels contributes to airway smooth muscle tension via Ca(2+) influx
passing through voltage-dependent Ca(2+) (VDC) channels. The Gs/KCa/VDC channel
linkage is a key process in not only physiological effects, but also in
dysfunction of beta2-adrenergic receptors and airway remodeling. Moreover, this
pathway is involved in the synergistic effects between beta2-adrenergic receptor
agonists and muscarinic receptor antagonists. Intrinsic efficacy is also an
important characteristic for both maintenance and loss of beta2-adrenergic
action. Allosteric modulators of G protein-coupled receptors contribute not only
to this synergistic effect between beta2-adrenergic and muscarinic M2 receptors,
but also to intrinsic efficacy. The effects of weak partial agonists are
suppressed by lowering receptor number, disordering receptor function, and
enhancing functional antagonism; in contrast, those of full or strong partial
agonists are not suppressed. Excessive exposure to full agonists causes beta2
adrenergic desensitization; in contrast, exposure to partial agonists does not
cause desensitization. Intrinsic efficacy may provide the rationale for the
clinical use of beta2-adrenergic receptor agonists in asthma and COPD. In
conclusion, the G protein/KCa linkage and intrinsic efficacy (allosteric effects)
may be therapeutic targets for research and development of novel agents against
both airway obstruction and airway remodeling.
PMID- 26432617
TI - Activation of endogenous antioxidants as a common therapeutic strategy against
cancer, neurodegeneration and cardiovascular diseases: A lesson learnt from DJ-1.
AB - This review aims at presenting a new concept pertaining to the development of
antioxidants, namely, to evolve from disease-oriented therapy to mechanism
oriented therapy. Using as our illustrative example is DJ-1, a homodimeric
protein that is ubiquitously expressed in a variety of mammalian tissues,
including the brain, and is found in the matrix and the intermembrane space of
the mitochondria. DJ-1 is known to be an endogenous antioxidant against cancer,
neurodegeneration and cardiovascular diseases, of which oxidative stress plays a
causal role. Interestingly, the mechanistic targets of DJ-1 as an antioxidant,
including Daxx, Nrf2, thioredoxin, glutathione, alpha-synuclein, PTEN/PI3K/Akt,
and Pink/Parkin are also associated with those oxidative stress-related diseases.
Furthermore, activators of DJ-1 are available in the form of mortalin,
phenylbutyrate and NAD(P)H: quinone oxidoreductase 1. It follows that activation
of DJ-1 as a common endogenous antioxidant provides a new strategy against
cancer, neurodegeneration and cardiovascular diseases. Since clinical trials on
exogenous application of the known antioxidants have basically failed, an
alternative approach would logically be to activate the endogenous antioxidants
that are already present in the appropriate cellular locale where elevated
oxidative stress is the culprit for the disease. At the same time, since
oxidative stress is a common denominator among cancer, neurodegeneration and
cardiovascular diseases, development of antioxidant therapy should target the
reduction in reactive oxygen species. Instead of focusing on disease-oriented
therapy, pharmaceutical companies should concentrate on developing agents and
dosing schemes for effective activation of the endogenous antioxidants that are
associated with a multitude of oxidative stress-related diseases (mechanism
oriented therapy).
PMID- 26432618
TI - Enhancement of indocyanine green stability and cellular uptake by incorporating
cationic lipid into indocyanine green-loaded nanoemulsions.
AB - Indocyanine green (ICG) is a near-infrared optical dye approved by the Food and
Drug Administration. ICG has been investigated as a simultaneous color and
fluorescence-imaging tracer for the intraoperative identification of sentinel
lymph nodes, but its use has recently expanded to include application as a
photosensitizer for the local photodynamic/thermal treatment of identified lymph
node metastases. The current study was designed to develop an ICG-loaded
nanoemulsion as an effective agent for both the diagnosis and treatment of lymph
node metastases. Incorporating the cationic lipid stearylamine (SA) together with
ICG in the shell of nanoemulsions did not affect the loaded ICG concentration,
but changed the surface charge of nanoemulsions from a negative to a positive
value and improved the physical stability of nanoemulsions. Loading ICG into SA
incorporated nanoemulsions more effectively blocked the aggregation and
degradation of ICG compared to loading in SA-free nanoemulsions. SA incorporation
also enhanced tumor cell uptake of ICG-loaded nanoemulsions, resulting in greater
cell killing upon light irradiation. After subcutaneous injection into the
footpad of mice, SA-incorporated nanoemulsions increased the concentration of ICG
accumulated in popliteal lymph nodes to a greater extent than SA-free
nanoemulsions without affecting the kinetics of lymph node uptake of
nanoemulsions. These multiple beneficial effects of incorporating SA in
nanoemulsions are likely attributable to the electrostatic interaction between
anionic ICG and cationic SA, as well as the change in the nanoemulsion surface
charge from negative to positive. Our findings indicate that SA-incorporated
nanoemulsions are promising ICG carriers for combined diagnosis and treatment of
lymph node metastases.
PMID- 26432619
TI - Silica nanowire conjugated with loop-shaped oligonucleotides: A new structure to
silence cysteine proteinase gene in Leishmania tropica.
AB - The main aim of this study was to evaluate the capability of silica nanowire
conjugated with loop-shaped oligonucleotides (SNWCLSOs) to silence cysteine
proteinase b (Cpb) gene in Leishmania (L) tropica. On the other hand, its
toxicity on amastigotes and mouse peritoneal macrophages was evaluated by 5
diphenyl-tetrazolium bromide (MTT) assay. For control, two loop-shaped
oligonucleotides (LSO) were considered. LSO1 and LSO2 were 5'-NH2
cccccaaaaaaaaaaaaaaaaaaaaaaaaaggggg-COOH-3' and LSO2: 5'-NH2
cccccttttttttttttttttttttttttttttttttttttttggggg-COOH-3', respectively. After 72
h incubation at 37 degrees C, AMSNW, LSO1, and LSO2 had no remarkable toxicity
on L. tropica amastigote (2 * 10(5)/mL) and mouse peritoneal macrophages (2 *
10(5)/mL). In case of SNWCLSOs, they had high toxicity on L. tropica amastigote,
but they had no effect on mouse peritoneal macrophages. At concentrations of 1,
10, and 25 MUg/mL, AMSNW, LSO1 and LSO2 had no effect on the gene expression.
But, at concentration of 50 and 100 MUg/mL, decrease of gene expression was
observed. In case of SNWCLSOs, they could dramatically decrease the gene
expression. It could be concluded that since SNWCLSOs could silence Cpb gene with
no remarkable toxicity, they are good choice for treat cutaneous leishmaniasis in
future. As a new agent, it must be checked in vivo.
PMID- 26432620
TI - A novel infant milk formula concept: Mimicking the human milk fat globule
structure.
AB - Human milk (HM) provides all nutrients to support an optimal growth and
development of the neonate. The composition and structure of HM lipids, the most
important energy provider, have an impact on the digestion, uptake and metabolism
of lipids. In HM, the lipids are present in the form of dispersed fat globules:
large fat droplets enveloped by a phospholipid membrane. Currently, infant milk
formula (Control IMF) contains small fat droplets primarily coated by proteins.
Recently, a novel IMF concept (Concept IMF) was developed with a different lipid
architecture, Nuturis((r)), comprising large fat droplets with a phospholipid
coating. Confocal laser scanning microscopy (CLSM), with appropriate fluorescent
probes, and transmission electron microscopy were used to determine and compare
the interfacial composition and structure of HM fat globules, Concept IMF fat
droplets and Control IMF fat droplets. The presence of a trilayer-structured HM
fat globule membrane, composed of phospholipids, proteins, glycoproteins and
cholesterol, was confirmed; in addition exosome-like vesicles are observed within
cytoplasmic crescents. The Control IMF fat droplets had a thick protein-only
interface. The Concept IMF fat droplets showed a very thin interface composed of
a mixture of phospholipids, proteins and cholesterol. Furthermore, the Concept
IMF contained fragments of milk fat globule membrane, which has been suggested to
have potential biological functions in infants. By mimicking more closely the
structure and composition of HM fat globules, this novel IMF concept with
Nuturis((r)) may have metabolic and digestive properties that are more similar to
HM compared to Control IMF.
PMID- 26432621
TI - Contrast and response gain control depend on cortical map architecture.
AB - Visual cortical neurons are sensitive to visual stimulus contrast and most cells
adapt their sensitivity to the prevailing visual environment. Specifically, they
match the steepest region of their contrast response function to the prevailing
contrast (contrast gain control), and reduce spike rates to limit saturation
(response gain control). Most neurons are also tuned for stimulus orientation,
and neurons with similar orientation preference are clustered together into iso
orientation zones arranged around pinwheels, i.e. points where all orientations
are represented. Here we investigated the relationship between the contrast
adaptation properties of neurons and their location relative to pinwheels in the
orientation preference map. We measured orientation preference maps in cat cortex
using optical intrinsic signal imaging. We then characterized the contrast
adaptation properties of single neurons located close to pinwheels, in iso
orientation zones, and at regions in between. We found little evidence of
differential contrast sensitivity of neurons adapted to zero contrast. However,
after adaptation to their preferred orientation at high contrast, changes in both
contrast and response gain were greater for neurons near pinwheels compared with
other map regions. Therefore, in the adapted state, which is probably typical
during natural viewing, there is a spatial map of contrast sensitivity that is
associated with the orientation preference map. This differential adaptation
revealed a new dimension of cortical functional organization, linking the
contrast adaptation of cells with the orientation preference of their nearest
neighbours.
PMID- 26432622
TI - Effects of Physical Exercise on Health and Well-Being of Individuals Living With
a Dementia in Nursing Homes: A Systematic Review.
AB - BACKGROUND: Physical exercise interventions have benefits for older individuals
and improve the health and well-being of individuals living with a dementia,
specifically those living in nursing homes. PURPOSE: Report evidence from
randomized controlled trials and cluster randomized control trials that evaluated
the effects of physical exercise interventions on individuals living with a
dementia in nursing homes. DATA SOURCES: Web of Science, Scopus, Science Direct,
Academic Search Complete, Proquest Central, British Medical Journal Database,
PubMed, Cochrane Library, PEDro, Informit, Informa, and Nursing Consult were
searched for relevant clinical trials and snowballing of recommended studies.
STUDY SELECTION: One reviewer screened articles on inclusion criteria and
identified relevant studies. DATA EXTRACTION: Data extraction was performed by 1
reviewer and checked by second and third reviewers. Two authors assessed the
methodological quality and risk of bias of the relevant studies. DATA SYNTHESIS:
Twelve study populations consisting of individuals living with a dementia in
nursing homes were included (n = 901). Different types of physical exercises were
undertaken: multimodal (n = 6), walking (n = 5), music and movement (n = 2), and
hand exercises (n = 1). The parameters of the interventions varied across the
studies. Most of the studies reported significant positive effects of physical
exercise on cognition, agitation, mood, mobility, and functional ability for
individuals living with dementia in nursing homes. LIMITATIONS: The main
limitations were the heterogeneity of design, small samples, and short
interventions. CONCLUSIONS: There is emerging evidence that physical exercise
significantly benefits individuals living with a dementia in nursing homes.
Higher quality research is required adopting more rigorous methods, including
longer interventions and larger samples to determine optimum parameters of the
physical exercise interventions evaluated.
PMID- 26432623
TI - Sliding Scale Insulin vs Basal-Bolus Insulin Therapy in Long-Term Care: A 21-Day
Randomized Controlled Trial Comparing Efficacy, Safety and Feasibility.
AB - INTRODUCTION: Sliding scale insulin (SSI) therapy remains a common means of
insulin therapy in long-term care (LTC) for the management of type 2 diabetes
mellitus, despite current recommendations not supportive of the form of therapy
today. Lack of randomized trial data on the efficacy and safety of basal-bolus
insulin (B-BI) therapy in nursing home residents may have precluded this form of
insulin administration in the LTC setting. Our study is a comparison of the
efficacy of SSI (control) and B-BI (intervention) therapies during a 21-day
intervention trial in older nursing home residents. METHODS: Fourteen LTC
facilities in the US participated; 110 residents with type 2 diabetes volunteered
to participate; 35 failed inclusion criteria, 75 signed informed written consent,
and 11 were discharged to home/hospital or withdrew consent; data from 64
participants are reported. Recent fasting blood glucose (FBG), hemoglobin A1c,
and chemistries were obtained. Four glucose readings (prior to breakfast, lunch,
dinner, and bedtime), oral antiglycemic drug, and insulin doses and changes, and
all adverse events/serious adverse events, both those related to glucose control
[hypoglycemic (<70 mg/dL) and hyperglycemic (>200 mg/dL) episodes] and those
unrelated, were recorded daily. Patients were randomized to either remain on SSI
or be shifted to the B-BI group. RESULTS: Nursing home residents 80 +/- 8
(standard deviation) years, 66% female participated; Control and Intervention
participants had similar age, gender, race distributions, comorbidity, and 3-day
average pretrial FBG levels (all P > .05). At study end, B-BI volunteers had
significantly lower 3-day average FBG levels vs pretrial (P = .0231) while SSI
participants had no change in 3-day average FBG (P > .05). During the trial,
participants from both groups had similar rates of hypoglycemia, hyperglycemia,
other adverse events, and hospitalizations (serious adverse events) unrelated to
glucose control (all P > .05). CONCLUSIONS: B-BI therapy produced significantly
lower average FBG levels after 21 days compared with SSI therapy; both groups had
similar rates of hypo- and hyperglycemia. Switching to B-BI therapy is feasible,
safe, and effective in the LTC setting.
PMID- 26432624
TI - Differences in Case Conferences in Dementia Specific vs Traditional Care Units in
German Nursing Homes: Results from a Cross-Sectional Study.
AB - OBJECTIVES: To investigate differences in the provision and performance of case
conferences for people with dementia between dementia special care units (DSCUs)
and traditional care units (TCUs) in nursing homes. Because DSCUs employ more
staff, we expect the likelihood of the provision of case conferences to be higher
in DSCUs. DESIGN: Observational cross-sectional study. Residents from DSCUs and
TCUs were compared using genetic propensity score matching over all of the
observed potential covariates, including the characteristics that served as
admission criteria for DSCUs. Because of the multisite structure of the data,
clustering was accounted for with a generalized mixed model. SETTING: DSCUs are
defined as units within nursing homes that offer care exclusively to residents
with dementia and that charge higher rates for the specialized care provided.
TCUs are defined as care units for residents with and without dementia.
PARTICIPANTS: A matched sample was drawn out of a convenience sample of 1808
residents from 51 nursing homes. It consisted of 264 residents from 16 DSCUs and
264 residents from 48 TCUs. INTERVENTIONS: None. MEASUREMENTS: Data regarding the
provision of case conferences were collected by the nurses using the Dementia
Care Questionnaire. Other collected data included challenging behavior
(Neuropsychiatric Inventory Questionnaire), mobility (Physical Self-Maintenance
Scale), cognitive impairment (Dementia Screening Scale), and sociodemographic
information. RESULTS: In the DSCU group, case conferences were provided to 91% (n
= 224) of the residents; in the TCU group, 82.5% (n = 203) received a case
conference. After adjusting for clustering, no significant difference between
DSCUs and non-DSCUs was found. The topic "challenging behaviors" was discussed
more often in case conferences in TCUs. CONCLUSIONS: Case conferences are a
widespread intervention in German nursing homes, including both DSCUs and TCUs.
The provision of a case conference is not a special feature of DSCUs.
PMID- 26432625
TI - An Administrator's Perspective on the Organization of Physical Activity for Older
Adults in Long-Term Care Facilities.
AB - BACKGROUND: The positive influence of physical activity (PA) on health is well
documented. Even at old age, PA remains useful but participation in PA decreases
with age. In long-term care facilities (LTCFs), PA appears to be reduced to a
bare minimum. Because administrators have a key role in developing the care
policy of LTCFs, it is important that they support the organization of PA in
LTCFs. OBJECTIVE: The main objective of this mixed-method study was to identify
motivators and barriers for organizing PA in LTCFs according to administrators. A
secondary goal was to examine the knowledge of the World Health Organization
(WHO) guidelines regarding PA and to reveal potential motivators and barriers for
the implementation of the guidelines. METHODS: First, 24 administrators completed
semistructured interviews. Data were analyzed using the deductive approach of
qualitative content analysis. The obtained motivators and barriers were
categorized on 3 different levels (intrapersonal, interpersonal, and community)
according to the socioecological model by 2 independent reviewers; conflicts were
resolved with a third researcher. Next, 127 administrators of Flemish (Belgium)
LTCFs completed an online questionnaire survey containing open-ended, unique, and
multiple choice questions regarding the LTCFs, PA, and the WHO guidelines, as
well as statements (scored on a 5-point Likert scale) regarding perceived
motivators and barriers for organizing PA sessions in the LTCF. RESULTS: In the
qualitative component, the administrators reported 31 motivators and 24 barriers
for organizing PA in the LTCF. In the survey, maintaining or enhancing general
health of the residents (98%) and improving the psychological well-being of the
residents were marked as key motivators at the intrapersonal level. The
administrators (97%) were convinced that PA is a useful way to spend time for
LTCF residents. Encouraging social contact (94%) and countering loneliness (86%)
are the motivators cited at the interpersonal level. At the community level, the
infrastructure of the facility (91%) and adequate and sufficient material (88%)
are the main motivators. The barriers that were presented to the participants
were scored as less important. The majority of the administrators (83%) are not
familiar with the WHO guidelines for PA; 70% of the participants believe that the
guidelines are useful, but only 40% is convinced that it is realistic to
implement the guidelines in an LTCF. CONCLUSIONS: This study described different
motivators and barriers for administrators to organize PA in LTCFs. Contrary to
other studies, lack of staff, lack of adequate equipment, and lack of financial
resources were rejected as potential barriers for organizing PA. Despite the fact
that administrators were not familiar with the WHO guidelines for PA, they
believed that the guidelines are useful. The participants reported several
barriers for implementation of the guidelines. Administrators of LTCFs are
motivated to implement the guidelines if PA can be integrated in daily activities
and education of LTCF staff regarding PA is provided.
PMID- 26432626
TI - Psychoimmunology and Aging: A Tribute to George Freeman Solomon.
PMID- 26432627
TI - Update on a proper use of systemic fluoroquinolones in adult patients
(ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin.
SPILF.).
PMID- 26432628
TI - Extracorporeal CO2 removal: Technical and physiological fundaments and principal
indications.
AB - In recent years, technological improvements have reduced the complexity of
extracorporeal membrane oxygenation devices. This have enabled the development of
specific devices for the extracorporeal removal of CO2. These devices have a
simpler configuration than extracorporeal membrane oxygenation devices and uses
lower blood flows which could reduce the potential complications. Experimental
studies have demonstrated the feasibility, efficacy and safety of extracorporeal
removal of CO2 and some of its effects in humans. This technique was initially
conceived as an adjunct therapy in patients with severe acute respiratory
distress syndrome, as a tool to optimize protective ventilation. More recently,
the use of this technique has allowed the emergence of a relatively new concept
called "tra-protective ventilation"whose effects are still to be determined. In
addition, the extracorporeal removal of CO2 has been used in patients with
exacerbated hypercapnic respiratory failure with promising results. In this
review we will describe the physiological and technical fundamentals of this
therapy and its variants as well as an overview of the available clinical
evidence, focused on its current potential.
PMID- 26432629
TI - The Hruska postulate of Crohn's disease.
AB - Crohn's disease is due to the loss of immunological tolerance within the
gastrointestinal tract to the antigenic array of Mycobacterium avium subspecies
paratuberculosis (MAP) and closely related polymorphic variants. The loss of
immune tolerance results in an effector cytokine responsive upon re-exposure to
MAP. For immune tolerance to MAP to be induced, infection must occur when
acquired immunity is markedly underdeveloped.
PMID- 26432630
TI - A hypothesis on the conflicting results of angiotensin converting enzyme
inhibitor in the prevention of contrast-induced nephropathy.
AB - Contrast-induced nephropathy (CIN) is regarded as acute tubular necrosis
resulting from the cytotoxicity of contrast media and the medullary hypoxia
linking to the interplay of vasoconstriction and vasodilatation. Saline infusion
may prevent CIN by inhibiting renin release and thus production of angiotensin II
(ANG II), a vasoconstrictor, from angiotensin I (ANG I). Yet the use of
angiotensin converting enzyme inhibitor (ACEI) yields conflicting results in the
prevention of CIN. We hypothesise that ACEI will be useful for CIN prevention
when the saline infusion is insufficient, useless when the saline infusion is
sufficient, and counterproductive when the saline infusion is excessive,
respectively. When the production of ANG I and thus ANG II is insufficiently
inhibited by insufficient saline infusion, ACEI may help prevent CIN by
conferring extra inhibition on the production of ANG II from ANG I. The
counterproductive effect may result from ACEI blocking the generation of
angiotensin 1-7, a potent vasodilator, from angiotensin 1-9 whose precursor, ANG
I, is excessively diminished by excessive saline infusion. Clinical data suggest
that normal saline infusion at a rate of 1 ml/kg/h for 12 h, 1 ml/kg/h for 6 h,
and 2 ml/kg/h for 6 h before and after contrast injection provide sufficient,
insufficient, and excessive hydration in the prevention of CIN, respectively. The
mainstream guideline is to stop ACEI and provide sufficient hydration for CIN
prevention. Alternatively one may continue to have ACEI but the use of normal
saline infusion must be limited to 1 ml/kg/h for 6 h before and after contrast
injection.
PMID- 26432631
TI - Cutis Marmorata skin decompression sickness is a manifestation of brainstem
bubble embolization, not of local skin bubbles.
AB - "Cutis Marmorata" skin symptoms after diving, most frequently in the form of an
itching or painful cutaneous red-bluish discoloration are commonly regarded as a
mild form of decompression sickness (DCS), and treated with oxygen inhalation
without reverting to hyperbaric recompression treatment. It has been observed
that the occurrence of Cutis Marmorata is frequently associated with the presence
of a Patent Foramen Ovale (PFO) of the heart, and indeed, with a properly
executed contrast echocardiographic technique, these patients have an almost 100%
prevalence of PFO. Only occasionally, Cutis Marmorata is accompanied by other
symptoms of DCS. These symptoms usually are in the form of visual distortions,
vertigo, or mild, vague but generalized cerebral dysfunction (such as abnormal
fatigue, clumsiness, concentration problems). The pathogenesis of these other
manifestations is clearly emboligenic, and we hypothesize that Cutis Marmorata is
also a manifestation of gas bubbles embolizing the brain stem: the site of
autonomic nervous system regulation of skin blood vessel dilation and
constriction. The consequences of this hypothesis are that Cutis Marmorata skin
decompression sickness should no longer be considered a mild, innocuous form but
rather a serious, neurological form and treated accordingly.
PMID- 26432632
TI - Comparison of Switching and Biofilm Formation between MTL-Homozygous Strains of
Candida albicans and Candida dubliniensis.
AB - Candida albicans and Candida dubliniensis are highly related species that share
the same main developmental programs. In C. albicans, it has been demonstrated
that the biofilms formed by strains heterozygous and homozygous at the mating
type locus (MTL) differ functionally, but studies rarely identify the MTL
configuration. This becomes a particular problem in studies of C. dubliniensis,
given that one-third of natural strains are MTL homozygous. For that reason, we
have analyzed MTL-homozygous strains of C. dubliniensis for their capacity to
switch from white to opaque, the stability of the opaque phenotype, CO2 induction
of switching, pheromone induction of adhesion, the effects of minority opaque
cells on biofilm thickness and dry weight, and biofilm architecture in comparison
with C. albicans. Our results reveal that C. dubliniensis strains switch to
opaque at lower average frequencies, exhibit a far lower level of opaque phase
stability, are not stimulated to switch by high CO2, exhibit more variability in
biofilm architecture, and most notably, form mature biofilms composed
predominately of pseudohyphae rather than true hyphae. Therefore, while several
traits of MTL-homozygous strains of C. dubliniensis appear to be degenerating or
have been lost, others, most notably several related to biofilm formation, have
been conserved. Within this context, the possibility is considered that C.
dubliniensis is transitioning from a hypha-dominated to a pseudohypha-dominated
biofilm and that aspects of C. dubliniensis colonization may provide insights
into the selective pressures that are involved.
PMID- 26432633
TI - Saccharomyces cerevisiae Is Dependent on Vesicular Traffic between the Golgi
Apparatus and the Vacuole When Inositolphosphorylceramide Synthase Aur1 Is
Inactivated.
AB - Inositolphosphorylceramide (IPC) and its mannosylated derivatives are the only
complex sphingolipids of yeast. Their synthesis can be reduced by aureobasidin A
(AbA), which specifically inhibits the IPC synthase Aur1. AbA reportedly, by
diminishing IPC levels, causes endoplasmic reticulum (ER) stress, an increase in
cytosolic calcium, reactive oxygen production, and mitochondrial damage leading
to apoptosis. We found that when Aur1 is gradually depleted by transcriptional
downregulation, the accumulation of ceramides becomes a major hindrance to cell
survival. Overexpression of the alkaline ceramidase YPC1 rescues cells under this
condition. We established hydroxylated C26 fatty acids as a reliable hallmark of
ceramide hydrolysis. Such hydrolysis occurs only when YPC1 is overexpressed. In
contrast, overexpression of YPC1 has no beneficial effect when Aur1 is acutely
repressed by AbA. A high-throughput genetic screen revealed that vesicle-mediated
transport between Golgi apparatus, endosomes, and vacuole becomes crucial for
survival when Aur1 is repressed, irrespective of the mode of repression. In
addition, vacuolar acidification becomes essential when cells are acutely
stressed by AbA, and quinacrine uptake into vacuoles shows that AbA activates
vacuolar acidification. The antioxidant N-acetylcysteine does not improve cell
growth on AbA, indicating that reactive oxygen radicals induced by AbA play a
minor role in its toxicity. AbA strongly induces the cell wall integrity pathway,
but osmotic support does not improve the viability of wild-type cells on AbA.
Altogether, the data support and refine current models of AbA-mediated cell death
and add vacuolar protein transport and acidification as novel critical elements
of stress resistance.
PMID- 26432634
TI - Yeast Integral Membrane Proteins Apq12, Brl1, and Brr6 Form a Complex Important
for Regulation of Membrane Homeostasis and Nuclear Pore Complex Biogenesis.
AB - Proper functioning of intracellular membranes is critical for many cellular
processes. A key feature of membranes is their ability to adapt to changes in
environmental conditions by adjusting their composition so as to maintain
constant biophysical properties, including fluidity and flexibility. Similar
changes in the biophysical properties of membranes likely occur when
intracellular processes, such as vesicle formation and fusion, require dramatic
changes in membrane curvature. Similar modifications must also be made when
nuclear pore complexes (NPCs) are constructed within the existing nuclear
membrane, as occurs during interphase in all eukaryotes. Here we report on the
role of the essential nuclear envelope/endoplasmic reticulum (NE/ER) protein Brl1
in regulating the membrane composition of the NE/ER. We show that Brl1 and two
other proteins characterized previously-Brr6, which is closely related to Brl1,
and Apq12-function together and are required for lipid homeostasis. All three
transmembrane proteins are localized to the NE and can be coprecipitated. As has
been shown for mutations affecting Brr6 and Apq12, mutations in Brl1 lead to
defects in lipid metabolism, increased sensitivity to drugs that inhibit enzymes
involved in lipid synthesis, and strong genetic interactions with mutations
affecting lipid metabolism. Mutations affecting Brl1 or Brr6 or the absence of
Apq12 leads to hyperfluid membranes, because mutant cells are hypersensitive to
agents that increase membrane fluidity. We suggest that the defects in nuclear
pore complex biogenesis and mRNA export seen in these mutants are consequences of
defects in maintaining the biophysical properties of the NE.
PMID- 26432635
TI - Incidence of postoperative shivering comparing remifentanil with other opioids: a
meta-analysis.
AB - STUDY OBJECTIVE: To determine whether the administration of remifentanil
increases the incidence of postoperative shivering in comparison with the
administration of alfentanil, fentanyl, or sufentanil. DESIGN: Meta-analysis.
SETTING: Operating room and postanesthesia care unit. MEASUREMENTS: We performed
a computerized search of articles on PubMed, MEDLINE, and Scopus. Meta-analysis
was performed using Review Manager and the DerSimonian and Laird random-effects
model. The pooled effect estimates for binary variables were calculated as
relative risk (RR) values with 95% confidence intervals (CIs). MAIN RESULTS:
Eighteen randomized controlled trials met our inclusion criteria. Remifentanil
was associated with a significantly increased incidence of postoperative
shivering compared with other opioids (RR=2.17; CI, 1.76-2.68; P<.00001;
I(2)=0.00%). A subgroup analysis of remifentanil compared with alfentanil,
fentanyl, or sufentanil showed that only sufentanil had a similar rate of
postoperative shivering incidence (RR=2.13; CI, 0.67-6.74; P=.20; I(2)=0.00%).
Remifentanil administration was associated with a significant increase in the
incidence of postoperative shivering compared with the administration of other
opioids when both propofol (RR=2.44; CI, 1.52-3.92; P=.0002; I(2)=0.00%) and
inhalation anesthesia drugs (RR=2.45; CI, 1.46-4.11; P=.0007; I(2)=0.00%) were
used for anesthesia maintenance. In addition, the administration of remifentanil
at both low (RR=2.06; CI, 1.63-2.60; P<.00001; I(2)=0.00%) and high dosages
(RR=2.77; CI, 1.67-4.57; P<.0001; I(2)=0.00%) was associated with a significant
increase in the incidence of postoperative shivering compared with the
administration of other opioids. CONCLUSIONS: Our meta-analysis showed that
remifentanil was associated with an increased incidence of postoperative
shivering compared with alfentanil or fentanyl, but no significant difference was
seen when compared with sufentanil.
PMID- 26432636
TI - The Phytosiderophore Efflux Transporter TOM2 Is Involved in Metal Transport in
Rice.
AB - Iron is an essential metal element for all living organisms. Graminaceous plants
produce and secrete mugineic acid family phytosiderophores from their roots to
acquire iron in the soil. Phytosiderophores chelate and solubilize insoluble iron
hydroxide in the soil. Subsequently, plants take up iron-phytosiderophore
complexes through specific transporters on the root cell membrane.
Phytosiderophores are also thought to be important for the internal transport of
various transition metals, including iron. In this study, we analyzed TOM2 and
TOM3, rice homologs of transporter of mugineic acid family phytosiderophores 1
(TOM1), a crucial efflux transporter directly involved in phytosiderophore
secretion into the soil. Transgenic rice analysis using promoter-beta
glucuronidase revealed that TOM2 was expressed in tissues involved in metal
translocation, whereas TOM3 was expressed only in restricted parts of the plant.
Strong TOM2 expression was observed in developing tissues during seed maturation
and germination, whereas TOM3 expression was weak during seed maturation.
Transgenic rice in which TOM2 expression was repressed by RNA interference showed
growth defects compared with non-transformants and TOM3-repressed rice. Xenopus
laevis oocytes expressing TOM2 released (14)C-labeled deoxymugineic acid, the
initial phytosiderophore compound in the biosynthetic pathway in rice. In onion
epidermal and rice root cells, the TOM2-GFP fusion protein localized to the cell
membrane, indicating that the TOM2 protein is a transporter for phytosiderophore
efflux to the cell exterior. Our results indicate that TOM2 is involved in the
internal transport of deoxymugineic acid, which is required for normal plant
growth.
PMID- 26432637
TI - Procollagen Lysyl Hydroxylase 2 Expression Is Regulated by an Alternative
Downstream Transforming Growth Factor beta-1 Activation Mechanism.
AB - PLOD2 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2) hydroxylates lysine
residues in collagen telopeptides and is essential for collagen pyridinoline
cross-link formation. PLOD2 expression and subsequent pyridinoline cross-links
are increased in fibrotic pathologies by transforming growth factor beta-1
(TGFbeta1). In this report we examined the molecular processes underlying
TGFbeta1-induced PLOD2 expression. We found that binding of the TGFbeta1 pathway
related transcription factors SMAD3 and SP1-mediated TGFbeta1 enhanced PLOD2
expression and could be correlated to an increase of acetylated histone H3 and H4
at the PLOD2 promoter. Interestingly, the classical co-activators of SMAD3
complexes, p300 and CBP, were not responsible for the enhanced H3 and H4
acetylation. Depletion of SMAD3 reduced PLOD2 acetylated H3 and H4, indicating
that another as of yet unidentified histone acetyltransferase binds to SMAD3 at
PLOD2. Assessing histone methylation marks at the PLOD2 promoter depicted an
increase of the active histone mark H3K79me2, a decrease of the repressive
H4K20me3 mark, but no role for the generally strong transcription-related
modifications: H3K4me3, H3K9me3 and H3K27me3. Collectively, our findings reveal
that TGFbeta1 induces a SP1- and SMAD3-dependent recruitment of histone modifying
enzymes to the PLOD2 promoter other than the currently known TGFbeta1 downstream
co-activators and epigenetic modifications. This also suggests that additional
activation strategies are used downstream of the TGFbeta1 pathway, and hence
their unraveling could be of great importance to fully understand TGFbeta1
activation of genes.
PMID- 26432638
TI - The Regulatory and Kinase Domains but Not the Interdomain Linker Determine Human
Double-stranded RNA-activated Kinase (PKR) Sensitivity to Inhibition by Viral Non
coding RNAs.
AB - Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is an important
component of the innate immune system that presents a crucial first line of
defense against viral infection. PKR has a modular architecture comprising a
regulatory N-terminal dsRNA binding domain and a C-terminal kinase domain
interposed by an unstructured ~80-residue interdomain linker (IDL). Guided by
sequence alignment, we created IDL deletions in human PKR (hPKR) and
regulatory/kinase domain swap human-rat chimeric PKRs to assess the contributions
of each domain and the IDL to regulation of the kinase activity by RNA. Using
circular dichroism spectroscopy, limited proteolysis, kinase assays, and
isothermal titration calorimetry, we show that each PKR protein is properly
folded with similar domain boundaries and that each exhibits comparable
polyinosinic-cytidylic (poly(rI:rC)) dsRNA activation profiles and binding
affinities for adenoviral virus-associated RNA I (VA RNAI) and HIV-1 trans
activation response (TAR) RNA. From these results we conclude that the IDL of PKR
is not required for RNA binding or mediating changes in protein conformation or
domain interactions necessary for PKR regulation by RNA. In contrast, inhibition
of rat PKR by VA RNAI and TAR RNA was found to be weaker than for hPKR by 7- and
>300-fold, respectively, and each human-rat chimeric domain-swapped protein
showed intermediate levels of inhibition. These findings indicate that PKR
sequence or structural elements in the kinase domain, present in hPKR but absent
in rat PKR, are exploited by viral non-coding RNAs to accomplish efficient
inhibition of PKR.
PMID- 26432639
TI - TAZ Protein Accumulation Is Negatively Regulated by YAP Abundance in Mammalian
Cells.
AB - The mammalian Hippo signaling pathway regulates cell growth and survival and is
frequently dysregulated in cancer. YAP and TAZ are transcriptional coactivators
that function as effectors of this signaling pathway. Aberrant YAP and TAZ
activity is reported in several human cancers, and normally the expression and
nuclear localization of these proteins is tightly regulated. We sought to
establish whether a direct relationship exists between YAP and TAZ. Using
knockdown and overexpression experiments we show YAP inversely regulates the
abundance of TAZ protein by proteasomal degradation. Interestingly this
phenomenon was uni-directional since TAZ expression did not affect YAP abundance.
Structure/function analyses suggest that YAP-induced TAZ degradation is a
consequence of YAP-targeted gene transcription involving TEAD factors. Subsequent
investigation of known regulators of TAZ degradation using specific inhibitors
revealed a role for heat shock protein 90 and glycogen synthase kinase 3 but not
casein kinase 1 nor LATS in YAP-mediated TAZ loss. Importantly, this phenomenon
is conserved from mouse to human; however, interestingly, different YAP isoforms
varied in their ability to degrade TAZ. Since shRNA-mediated TAZ depletion in
HeLa and D645 cells caused apoptotic cell death, we propose that isoform-specific
YAP-mediated TAZ degradation may contribute to the contradicting roles reported
for YAP overexpression. This study identifies a novel mechanism of TAZ regulation
by YAP, which has significant implications for our understanding of Hippo pathway
regulation, YAP-isoform specific signaling, and the role of these proteins in
cell proliferation, apoptosis, and tumorigenesis.
PMID- 26432641
TI - Crystal Structure of the Human Cytomegalovirus pUL50-pUL53 Core Nuclear Egress
Complex Provides Insight into a Unique Assembly Scaffold for Virus-Host Protein
Interactions.
AB - Nuclear replication of cytomegalovirus relies on elaborate mechanisms of
nucleocytoplasmic egress of viral particles. Thus, the role of two essential and
conserved viral nuclear egress proteins, pUL50 and pUL53, is pivotal. pUL50 and
pUL53 heterodimerize and form a core nuclear egress complex (NEC), which is
anchored to the inner nuclear membrane and provides a scaffold for the assembly
of a multimeric viral-cellular NEC. Here, we report the crystal structure of the
pUL50-pUL53 heterodimer (amino acids 1-175 and 50-292, respectively) at 2.44 A
resolution. Both proteins adopt a globular fold with mixed alpha and beta
secondary structure elements. pUL53-specific features include a zinc-binding site
and a hook-like N-terminal extension, the latter representing a hallmark element
of the pUL50-pUL53 interaction. The hook-like extension (amino acids 59-87)
embraces pUL50 and contributes 1510 A(2) to the total interface area (1880 A(2)).
The pUL50 structure overall resembles the recently published NMR structure of the
murine cytomegalovirus homolog pM50 but reveals a considerable repositioning of
the very C-terminal alpha-helix of pUL50 upon pUL53 binding. pUL53 shows
structural resemblance with the GHKL domain of bacterial sensory histidine
kinases. A close examination of the crystal structure indicates partial assembly
of pUL50-pUL53 heterodimers to hexameric ring-like structures possibly providing
additional scaffolding opportunities for NEC. In combination, the structural
information on pUL50-pUL53 considerably improves our understanding of the
mechanism of HCMV nuclear egress. It may also accelerate the validation of the
NEC as a unique target for developing a novel type of antiviral drug and improved
options of broad-spectrum antiherpesviral therapy.
PMID- 26432640
TI - Finding Channels.
PMID- 26432642
TI - A Novel alpha2/alpha4 Subtype-selective Positive Allosteric Modulator of
Nicotinic Acetylcholine Receptors Acting from the C-tail of an alpha Subunit.
AB - Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors
(nAChR) are important therapeutic candidates as well as valuable research tools.
We identified a novel type II PAM, (R)-7-bromo-N-(piperidin-3
yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which both increases activation and
reactivates desensitized nAChRs. This compound increases acetylcholine-evoked
responses of alpha2* and alpha4* nAChRs but is without effect on alpha3* or
alpha6* nAChRs (* indicates the presence of other nAChR subunits). Br-BPTC acts
from the C-terminal extracellular sequences of alpha4 subunits, which is also a
PAM site for steroid hormone estrogens such as 17beta-estradiol. Br-PBTC is much
more potent than estrogens. Like 17beta-estradiol, the non-steroid Br-PBTC only
requires one alpha4 subunit to potentiate nAChR function, and its potentiation is
stronger with more alpha4 subunits. This feature enables Br-BPTC to potentiate
activation of (alpha4beta2)(alpha6beta2)beta3 but not (alpha6beta2)2beta3 nAChRs.
Therefore, this compound is potentially useful in vivo for determining functions
of different alpha6* nAChR subtypes. Besides activation, Br-BPTC affects
desensitization of nAChRs induced by sustained exposure to agonists. After
minutes of exposure to agonists, Br-PBTC reactivated short term desensitized
nAChRs that have at least two alpha4 subunits but not those with only one. Three
alpha4 subunits were required for Br-BPTC to reactivate long term desensitized
nAChRs. These data suggest that higher PAM occupancy promotes channel opening
more efficiently and overcomes short and long term desensitization. This C
terminal extracellular domain could be a target for developing subtype or state
selective drugs for nAChRs.
PMID- 26432643
TI - Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the
Metabolic Profile of Human Cells.
AB - The mitochondrial NAD pool is particularly important for the maintenance of vital
cellular functions. Although at least in some fungi and plants, mitochondrial NAD
is imported from the cytosol by carrier proteins, in mammals, the mechanism of
how this organellar pool is generated has remained obscure. A transporter
mediating NAD import into mammalian mitochondria has not been identified. In
contrast, human recombinant NMNAT3 localizes to the mitochondrial matrix and is
able to catalyze NAD(+) biosynthesis in vitro. However, whether the endogenous
NMNAT3 protein is functionally effective at generating NAD(+) in mitochondria of
intact human cells still remains to be demonstrated. To modulate mitochondrial
NAD(+) content, we have expressed plant and yeast mitochondrial NAD(+) carriers
in human cells and observed a profound increase in mitochondrial NAD(+). None of
the closest human homologs of these carriers had any detectable effect on
mitochondrial NAD(+) content. Surprisingly, constitutive redistribution of NAD(+)
from the cytosol to the mitochondria by stable expression of the Arabidopsis
thaliana mitochondrial NAD(+) transporter NDT2 in HEK293 cells resulted in
dramatic growth retardation and a metabolic shift from oxidative phosphorylation
to glycolysis, despite the elevated mitochondrial NAD(+) levels. These results
suggest that a mitochondrial NAD(+) transporter, similar to the known one from A.
thaliana, is likely absent and could even be harmful in human cells. We provide
further support for the alternative possibility, namely intramitochondrial NAD(+)
synthesis, by demonstrating the presence of endogenous NMNAT3 in the mitochondria
of human cells.
PMID- 26432645
TI - Functions of plant-specific myosin XI: from intracellular motility to plant
postures.
AB - The plant-specific protein motor class myosin XI is known to function in rapid
bulk flow of the cytoplasm (cytoplasmic streaming) and in organellar movements.
Recent studies unveiled a wide range of physiological functions of myosin XI
motors, from intracellular motility to organ movements. Arabidopsis thaliana has
13 members of myosin XI class. In vegetative organs, myosins XIk, XI1, and XI2
primarily contribute to dynamics and spatial configurations of endoplasmic
reticulum that develops a tubular network in the cell periphery and thick strand
like structures in the inner cell regions. Myosin XI-i forms a nucleocytoplasmic
linker and is responsible for nuclear movement and shape. In addition to these
intracellular functions, myosin XIf together with myosin XIk is involved in the
fundamental nature of plants; the actin-myosin XI cytoskeleton regulates organ
straightening to adjust plant posture.
PMID- 26432644
TI - Phospholipase Ceta2 Activation Redirects Vesicle Trafficking by Regulating F
actin.
AB - PI(4,5)P2 localizes to sites of dense core vesicle exocytosis in neuroendocrine
cells and is required for Ca(2+)-triggered vesicle exocytosis, but the impact of
local PI(4,5)P2 hydrolysis on exocytosis is poorly understood. Previously, we
reported that Ca(2+)-dependent activation of phospholipase Ceta2 (PLCeta2)
catalyzes PI(4,5)P2 hydrolysis, which affected vesicle exocytosis by regulating
the activities of the lipid-dependent priming factors CAPS (also known as CADPS)
and ubiquitous Munc13-2 in PC12 cells. Here we describe an additional role for
PLCeta2 in vesicle exocytosis as a Ca(2+)-dependent regulator of the actin
cytoskeleton. Depolarization of neuroendocrine PC12 cells with 56 or 95 mm KCl
buffers increased peak Ca(2+) levels to ~400 or ~800 nm, respectively, but
elicited similar numbers of vesicle exocytic events. However, 56 mm K(+)
preferentially elicited the exocytosis of plasma membrane-resident vesicles,
whereas 95 mm K(+) preferentially elicited the exocytosis of cytoplasmic vesicles
arriving during stimulation. Depolarization with 95 mm K(+) but not with 56 mm
K(+) activated PLCeta2 to catalyze PI(4,5)P2 hydrolysis. The decrease in
PI(4,5)P2 promoted F-actin disassembly, which increased exocytosis of newly
arriving vesicles. Consistent with its role as a Ca(2+)-dependent regulator of
the cortical actin cytoskeleton, PLCeta2 localized with F-actin filaments. The
results highlight the importance of PI(4,5)P2 for coordinating cytoskeletal
dynamics with vesicle exocytosis and reveal a new role for PLCeta2 as a Ca(2+)
dependent regulator of F-actin dynamics and vesicle trafficking.
PMID- 26432647
TI - Design of the remede System Pivotal Trial: A Prospective, Randomized Study in the
Use of Respiratory Rhythm Management to Treat Central Sleep Apnea.
AB - BACKGROUND: Central sleep apnea is common in patients with cardiovascular disease
and worsens outcomes. There is a lack of established therapies for central sleep
apnea, and those available are limited by poor patient adherence and potentially
adverse cardiovascular effects, at least in a subset of patients. The remede
System (Respicardia, Minnetonka, Minnesota) is a new physiologic treatment that
uses transvenous phrenic nerve stimulation to contract the diaphragm, thereby
stabilizing gas exchange and restoring normal breathing throughout the sleep
period. METHODS: This is a prospective multicenter randomized trial with blinded
end points evaluating the safety and efficacy of the remede System. Up to 173
patients with central sleep apnea will be randomized 1:1 to remede System therapy
initiated at 1 month after implantation (treatment) or to an implanted remede
System that will remain inactive for 6 months (control). Primary efficacy end
point is the percentage of patients who experience a reduction in apnea-hypopnea
index by a >= 50% at 6 months (responder analysis). Primary safety end point is
freedom from serious adverse events through 12 months. Secondary end points
include sleep-disordered breathing parameters, sleep architecture, Epworth
Sleepiness Scale score, and Patient Global Assessment. CONCLUSIONS: This is the
1st randomized controlled trial of the safety and efficacy of the remede System
for the treatment of central sleep apnea.
PMID- 26432646
TI - Outcomes of Adult Patients With Congenital Heart Disease After Heart
Transplantation: Impact of Disease Type, Previous Thoracic Surgeries, and
Bystander Organ Dysfunction.
AB - BACKGROUND: Adults with congenital heart disease (CHD) are at increased risk for
adverse outcomes after heart transplantation (HT). However, small cohorts have
constrained the identification of factors associated with poor prognosis. We
hypothesized that number of sternotomies and bystander organ dysfunction would be
associated with an increased risk for early death after HT. METHODS AND RESULTS:
We performed a retrospective observational study of all adult CHD patients who
underwent HT at our institution from January 1997 to January 2014. Forty-eight
adult CHD patients were followed for a mean of 5 years. Diagnoses included
tetralogy of Fallot/pulmonary atresia/double-outlet right ventricle in 15 (31%),
D-transposition of the great arteries (TGA) in 10 (21%), tricuspid atresia/double
inlet left ventricle in 9 (19%), ventricular or atrial septal defect in 4 (8%),
heterotaxy in 3 (6%), congenitally corrected TGA in 2 (4%), and other diagnoses
in 5 (10%). Survival at both 1 and 5 years was 77%. According to multivariate
analysis, >=3 sternotomies (hazard ratio [HR] 8.5; P = .02) and Model for End
Stage Liver Disease Excluding International Normalized Ratio (MELD-XI) score >18
(HR 6.2; P = .01) were significant predictors of mortality. Failed Fontan surgery
was not a significant predictor of death (P = .19). CONCLUSIONS: In our cohort of
adult CHD patients undergoing HT, >=3 sternotomies and MELD-XI score >18 were
significantly associated with death. These findings may be important in patient
selection and decision regarding tolerable number of CHD surgeries before
considering HT.
PMID- 26432648
TI - [Delayed endoscopic reconstruction of the anterior wall of the frontal sinus:
Technical note].
AB - INTRODUCTION: Reconstruction of the anterior wall of the frontal sinus usually
requires a coronal incision. This extended approach may lead to paresthesia,
unsightly scars, bruises and cicatricial alopecia. These complications encouraged
several authors to endoscopic management of this kind of fractures. We present a
delayed technique of reconstruction of the anterior wall of the frontal sinus by
means of endoscopic hydroxyapatite filling. TECHNICAL NOTE: Two incisions were
performed behind the hair line. Subperiosteal dissection using a periosteal
elevator was performed. A 30 degrees angled endoscope was used to visualize the
depression. The latter was filled by Hydroset(r) (Stryker, USA) as a bone
substitute. DISCUSSION: In the absence of contra-indication, the reconstruction
of the anterior wall of the frontal sinus by means of endoscopic hydroxyapatite
filling has many advantages including uneventful outcome, reduction of the
hospital stay and a fast learning curve.
PMID- 26432649
TI - Improving the performance of factor VIII inhibitor tests in hemophilia A.
PMID- 26432650
TI - Clinical outcomes of venous thromboembolism with dalteparin therapy in multiple
myeloma patients.
AB - This study focused on the clinical outcomes in multiple myeloma (MM) patients
with venous thromboembolism (VTE) who received low-molecular-weight heparin
(dalteparin) therapy. Changes in D-dimer levels before and after VTE were also
evaluated. Among 549 patients treated with various chemotherapeutic agents, a
total of 52 (9.47%) patients including 32 newly diagnosed with MM and 16 with
relapsed/refractory MM developed VTE, 48 of whom received dalteparin. Among the
48 treated patients, 37 (77%) had proximal deep vein thrombosis (DVT), four had
(8%) pulmonary embolism (PE), and seven (15%) had both DVT and PE. In 32 patients
with available paired samples (at baseline and VTE occurrence), significant
conversion of D-dimer levels from 2.2 +/- 0.4 mg/L to 11.8 +/- 1.6 mg/L (P <
0.001) was observed, which decreased from 10.9 +/- 0.4 mg/L to 1.9 +/- 0.6 mg/L
one month after initiating dalteparin therapy. A total of 44 patients received
dalteparin with a median duration of 4.2 months (range, 2.7-9.4), and four
patients were discontinued early due to death (n = 3) and major bleeding (n = 1).
After a median follow-up of 9.0 months (range, 0.7-35.8) since the first VTE
episode, five patients showed recurrence of VTE with a cumulative incidence of
17.5 +/- 7.9%. Major bleeding occurred in three patients. In summary, dalteparin
seems to be a promising drug for the treatment of VTE in MM. In addition, the
significant difference in D-dimer levels observed before occurrence of VTE and
after dalteparin treatment may suggest the usefulness of D-dimer testing as a
surrogate marker for VTE in MM patients.
PMID- 26432651
TI - The plasma levels of protein Z-dependent protease inhibitor increase after
gynecological surgery independently of estrogen.
AB - INTRODUCTION: Protein Z (PZ)-dependent protease inhibitor (ZPI) is a serine
protease inhibitor that efficiently inhibits activated factor X when ZPI is in
complex with PZ. We previously reported significantly higher concentrations of
plasma ZPI (and PZ) in women during normal pregnancy than in non-pregnant women.
METHODS: We explored the possible contribution of estrogen to the ZPI levels in
patients with or without bilateral oophorectomy (OVX), which induces artificial
menopause where blood estrogen levels drastically decrease. One hundred ninety
one pre-menopausal Japanese women who underwent open hysterectomy owing to
neoplasms participated in this study and were divided into two groups: 98 OVX and
93 Non-OVX cases. Plasma ZPI was measured by ELISA. RESULTS AND CONCLUSION:
Contrary to our working hypothesis, plasma ZPI levels increased significantly in
the OVX group after surgery when compared with the pre-operation levels. When
these patients were individually analyzed, their ZPI value also rose
significantly from pre-operation to post-operation levels. In contrast, plasma PZ
levels remained unchanged. The significantly increased ZPI and unchanged PZ
levels were also observed in the Non-OVX group. The increased ZPI levels were not
significantly related to 17beta-estradiol, luteinizing hormone or follicular
stimulating hormone levels, clearly indicating that estrogen did not contribute
to the plasma ZPI concentrations. Typical acute phase reactants fibrinogen and C
reactive protein (CRP) were also significantly elevated after surgery in both OVX
and Non-OVX groups. However, only weakly significant linear relationships were
observed between ZPI and fibrinogen or CRP, indicating the presence of
alternative regulatory mechanisms underlying their plasma concentrations.
PMID- 26432652
TI - A collaborative approach to improve the assessment of physical health in adult
consumers with schizophrenia in Queensland mental health services.
AB - OBJECTIVE: The objective of this study was to apply a quality improvement
collaborative to increase the number of physical health assessments conducted
with consumers diagnosed with schizophrenia in adult community mental health
services across Queensland. METHOD: Sixteen adult mental health service
organisations voluntarily took part in the statewide collaborative initiative to
increase the number of physical health assessments completed on persons with a
diagnosis of schizophrenia spectrum disorders managed through the community
mental health service. RESULTS: Improvement in the physical health assessment
clinical indicator was demonstrated across the state over a 3-year period with an
increase in the number of physical health assessments recorded from 12% to 58%.
CONCLUSIONS: Significant improvements were made over a 3-year period by all
mental health services involved in the collaborative, supporting the application
of a quality improvement methodology to drive change across mental health
services.
PMID- 26432653
TI - Towards culturally appropriate assessment of Aboriginal and Torres Strait
Islander social and emotional well-being.
AB - OBJECTIVE: Identification of need for specialist assessment and the use of
relevant cultural information to inform mental health assessment and care are two
key factors in improving Aboriginal and Torres Strait Islander access to and
experience of mental health care. This paper describes the Here and Now
Aboriginal Assessment tool (HANAA) and the Cultural Information Gathering Tool
(CIGT), two instruments developed to be used respectively by non-mental health
clinicians and Aboriginal and Torres Strait Islander mental health workers.
METHOD: Following widespread consultations and feedback, two independent groups
of mental health clinicians based in Western Australia and Queensland were
involved in developing the HANAA and CIGT. RESULTS: Both the HANAA and CIGT fill
unmet needs in terms of instruments that can be used by non-specialists working
with Aboriginal and Torres Strait Islander people. CONCLUSIONS: Preliminary use
of the HANAA and CIGT suggests that they are well received, easy to deploy and
effective instruments that promote cultural security and communication with
Aboriginal and Torres Strait Islander people.
PMID- 26432654
TI - Mental health consequences of stress and trauma: allostatic load markers for
practice and policy with a focus on Indigenous health.
AB - OBJECTIVE: Mental health, well-being, and social life are intimately related as
is evident from the higher incidence of psychiatric illness in individuals
exposed to social stress and adversity. Several biological pathways linking
social adversity to health outcomes are heavily investigated in the aims of
facilitating early identification and prevention of adverse health outcomes. We
provide a practice-orientated overview of the allostatic load model and how it
relates to metabolic and cardiovascular comorbidity in psychiatric disorders.
CONCLUSIONS: Allostatic load brings together a set of neuroendocrine, metabolic,
immune and cardiovascular biomarkers that are elevated in individuals with
adverse early life experiences and are predictive of cardiovascular and metabolic
risk in psychiatric illness of critical importance for Indigenous Australians.
PMID- 26432655
TI - Determinants of the cost of capital for privately financed hospital projects in
the UK.
AB - Many governments make use of private finance contracts to deliver healthcare
infrastructure. Previous work has shown that the rate of return to investors in
these markets often exceeds the efficient level. Our focus is on the factors that
influence that return. We examine the effect of macroeconomic, project- and firm
level variables using a detailed sample of 84 UK private finance initiative (PFI)
contracts signed between 1997 and 2010. Of the above variables, macroeconomic
conditions and lead sponsor size are related to the investor return. However, our
results show a remarkable degree of stability in the return to investors over the
14-year period. We find evidence of a 'prevailing norm' that is robust to project
and firm-level variation. The sustainability of excess returns over a long
period is indicative of a concentrated market structure. We argue that
policymakers should consider new mechanisms for increasing competition in the
equity market, while ensuring that authorities have the specialist resources
required to negotiate efficient contract prices.
PMID- 26432656
TI - Prognostic factors in spinal chordoma: A systematic review.
AB - OBJECTIVE: Discovering reliable prognostic factors for spinal chordoma remains a
challenge. We attempted to identify evidence-based prognostic factors in the
literature since its inception and to establish pooled relative risks (RR) of
such factors. METHODS: MEDLINE and Embase search (inception to December 2014).
Two reviewers independently selected papers involving spinal chordoma prognostic
factors, and studied them for methodological quality and valuable new factors.
Subsequently, we attempted to pool the results. RESULTS: Of 1465 citations, we
studied 65 papers closely, and found several "new" prognostic factors. However,
only eight papers were of adequate quality for analysis. Location in the upper
cervical spine (pooled RR=5.46, 95% confidence interval [CI]: 2.23-13.34), worse
preoperative Frankel score (pooled RR=2.77, 95% CI: 1.73-4.42), intralesional
surgery (pooled RR=2.68, 95% CI: 1.66-4.32), greater extent of invasion (pooled
RR=5.09, 95% CI: 1.49-17.41), and revision surgery (pooled RR=2.42, 95% CI: 1.34
4.36) appeared to be independent factors for worse outcome. CONCLUSIONS: Despite
the wealth of literature available, disappointingly few papers are of sufficient
quality for drawing valid conclusions related to spinal chordoma prognostic
factors. The heterogeneity of the studies renders results pooling almost
impossible. More accurate individual prognostication requires methodologically
high-quality studies with more uniform study design and data reporting.
PMID- 26432657
TI - Connexin43 in retinal injury and disease.
AB - Gap junctions are specialized cell-to-cell contacts that allow the direct
transfer of small molecules between cells. A single gap junction channel consists
of two hemichannels, or connexons, each of which is composed of six connexin
protein subunits. Connexin43 is the most ubiquitously expressed isoform of the
connexin family and in the retina it is prevalent in astrocytes, Muller cells,
microglia, retinal pigment epithelium and endothelial cells. Prior to docking
with a neighboring cell, Connexin43 hemichannels have a low open probability as
open channels constitute a large, relatively non-specific membrane pore. However,
with injury and disease Connexin43 upregulation and hemichannel opening has been
implicated in all aspects of secondary damage, especially glial cell activation,
edema and loss of vascular integrity, leading to neuronal death. We here review
gap junctions and their roles in the retina, and then focus in on Connexin43 gap
junction channels in injury and disease. In particular, the effect of
pathological opening of gap junction hemichannels is described, and hemichannel
mediated loss of vascular integrity explained. This latter phenomenon underlies
retinal pigment epithelium loss and is a common feature in several retinal
diseases. Finally, Connexin43 channel roles in a number of retinal diseases
including macular degeneration, glaucoma and diabetic retinopathy are considered,
along with results from related animal models. A final section describes gap
junction channel modulation and the ocular delivery of potential therapeutic
molecules.
PMID- 26432658
TI - Letter to the Editor.
PMID- 26432661
TI - Pre-hospital pelvic girdle injury: Improving diagnostic accuracy in a physician
led trauma service.
AB - BACKGROUND: Examination of missed injuries in our physician-led pre-hospital
trauma service indicated that the significant injuries missed were often pelvic
fractures. We therefore conducted a study whose aim was to evaluate the pre
hospital diagnostic accuracy of pelvic girdle injuries, and how this would be
affected by implementing the pelvic injury treatment guidelines recently
published by the Faculty of Pre-Hospital Care. STUDY DESIGN: All blunt trauma
patients attended in a 5-month period were included in the study. The presence or
absence of pelvic girdle injury on computed tomography (CT) or, if unavailable,
pelvic X-ray was used as a primary outcome measure. A retrospective database and
case note review was conducted to identify patients who had pelvic binder applied
in the study period. For the purposes of the study, pelvic ring and acetabular
fractures were grouped together as patients with suspected pelvic girdle injury
that should be fitted with a pelvic binder in the pre-hospital setting. The
sensitivity and specificity, relating to the presence of pelvic girdle injury in
patients with pelvic binders, was calculated in order to determine pre-hospital
diagnostic accuracy. RESULTS: 785 patients were attended during the study period.
170 met the study inclusion criteria. 26 (15.3%) sustained a pelvic girdle
injury. 45 (26.5%) had a pelvic binder applied. There were eight missed fractures
(31%), of which the majority (six) sustained less severe injuries that were
managed non-operatively. Two patients required operative fixation. Radiological
images and/or reports were available on 169 (99.4%) patients. As a test of the
presence of pelvic fracture, pelvic binder application had a sensitivity of 0.69
(95% CI 0.50-0.85) and a specificity of 0.81 (95% CI 0.74-0.87). CONCLUSIONS:
Even with a careful clinical assessment and a low threshold for binder
application, this study highlights the problems of distracting injury when trying
to diagnose and manage pelvic fractures. By implementing the pelvic treatment
guidelines published by the Faculty of Pre-hospital Care, the missed injury rate
could be reduced from 31% to 8%.
PMID- 26432662
TI - Commentary on "Ten years of imaging for pulmonary embolism: too many scans or the
tip of an iceberg?".
PMID- 26432659
TI - Reactive oxygen species and mitochondria: A nexus of cellular homeostasis.
AB - Reactive oxygen species (ROS) are integral components of multiple cellular
pathways even though excessive or inappropriately localized ROS damage cells. ROS
function as anti-microbial effector molecules and as signaling molecules that
regulate such processes as NF-kB transcriptional activity, the production of DNA
based neutrophil extracellular traps (NETs), and autophagy. The main sources of
cellular ROS are mitochondria and NADPH oxidases (NOXs). In contrast to NOX
generated ROS, ROS produced in the mitochondria (mtROS) were initially considered
to be unwanted by-products of oxidative metabolism. Increasing evidence indicates
that mtROS have been incorporated into signaling pathways including those
regulating immune responses and autophagy. As metabolic hubs, mitochondria
facilitate crosstalk between the metabolic state of the cell with these pathways.
Mitochondria and ROS are thus a nexus of multiple pathways that determine the
response of cells to disruptions in cellular homeostasis such as infection,
sterile damage, and metabolic imbalance. In this review, we discuss the roles of
mitochondria in the generation of ROS-derived anti-microbial effectors, the
interplay of mitochondria and ROS with autophagy and the formation of DNA
extracellular traps, and activation of the NLRP3 inflammasome by ROS and
mitochondria.
PMID- 26432660
TI - Nitric oxide-mediated sensitization of resistant tumor cells to apoptosis by
chemo-immunotherapeutics.
AB - The generation of NO by the various NO synthases in normal and malignant tissues
is manifested by various biological effects that are involved in the regulation
of cell survival, differentiation and cell death. The role of NO in the cytotoxic
immune response was first revealed by demonstrating the induction of iNOS in
target cells by immune cytokines (e.g. IFN-gamma, IL-1, TNF-alpha, etc.) and
resulting in the sensitization of resistant tumor cells to death ligands-induced
apoptosis. Endogenous/exogenous NO mediated its immune sensitizing effect by
inhibiting NF-kappaBeta activity and downstream, inactivating the repressor
transcription factor YY1, which inhibited both Fas and DR5 expressions. In
addition, NO-mediated inhibition of NF-kappaBeta activity and inhibition
downstream of its anti-apoptotic gene targets sensitized the tumor cells to
apoptosis by chemotherapeutic drugs. We have identified in tumor cells a
dysregulated pro-survival/anti-apoptotic loop consisting of NF
kappaB/Snail/YY1/RKIP/PTEN and its modification by NO was responsible, in large,
for the reversal of chemo and immune resistance and sensitization to apoptotic
mechanisms by cytotoxic agents. Moreover, tumor cells treated with exogenous NO
donors resulted in the inhibition of NF-kappaBeta activity via S-nitrosylation of
p50 and p65, inhibition of Snail (NF-kappaBeta target gene), inhibition of
transcription repression by S-nitrosylation of YY1 and subsequent inhibition of
epithelial-mesenchymal transition (EMT), induction of RKIP (inhibition of the
transcription repressor Snail), and induction of PTEN (inhibition of the
repressors Snail and YY1). Further, each gene product modified by NO in the loop
was involved in chemo-immunosensitization. These above findings demonstrated that
NO donors interference in the regulatory circuitry result in chemo
immunosensitization and inhibition of EMT. Overall, these observations suggest
the potential anti-tumor therapeutic effect of NO donors in combination with
subtoxic chemo-immuno drugs. This combination acts on multiple facets including
reversal of chemo-immune resistance, and inhibition of both EMT and metastasis.
PMID- 26432663
TI - Aberrant Expression of Dynein light chain 1 (DYNLT1) is Associated with Human
Male Factor Infertility.
AB - DYNLT1 is a member of a gene family identified within the t-complex of the mouse,
which has been linked with male germ cell development and function in the mouse
and the fly. Though defects in the expression of this gene are associated with
male sterility in both these models, there has been no study examining its
association with spermatogenic defects in human males. In this study, we
evaluated the levels of DYNLT1 and its expression product in the germ cells of
fertile human males and males suffering from spermatogenic defects. We screened
fertile (n = 14), asthenozoospermic (n = 15), oligozoospermic (n = 20) and
teratozoospermic (n = 23) males using PCR and Western blot analysis.
Semiquantitative PCR indicated either undetectable or significantly lower levels
of expression of DYNLT1 in the germ cells from several patients from across the
three infertility syndrome groups, when compared with that of fertile controls.
DYNLT1 was localized on head, mid-piece, and tail segments of spermatozoa from
fertile males. Spermatozoa from infertile males presented either a total absence
of DYNLT1 or its absence in the tail region. Majority of the infertile
individuals showed negligible levels of localization of DYNLT1 on the
spermatozoa. Overexpression of DYNLT1 in GC1-spg cell line resulted in the up
regulation of several cytoskeletal proteins and molecular chaperones involved in
cell cycle regulation. Defective expression of DYNLT1 was associated with male
factor infertility syndromes in our study population. Proteome level changes in
GC1-spg cells overexpressing DYNLT1 were suggestive of its possible function in
germ cell development. We have discussed the implications of these observations
in the light of the known functions of DYNLT1, which included protein
trafficking, membrane vesiculation, cell cycle regulation, and stem cell
differentiation.
PMID- 26432664
TI - Central obesity early in adulthood may affect outcomes of hepatocellular
carcinoma.
PMID- 26432666
TI - Velocity of temperature and flowering time in wheat - assisting breeders to keep
pace with climate change.
AB - By accelerating crop development, warming climates may result in mismatches
between key sensitive growth stages and extreme climate events, with severe
consequences for crop yield and food security. Using recent estimates of gene
responses to vernalization and photoperiod in wheat, we modelled the flowering
times of all 'potential' genotypes as influenced by the velocity of climate
change across the Australian wheatbelt. In the period 1957-2010, seasonal
increases in temperature of 0.012 degrees C yr(-1) were recorded and changed
flowering time of a mid-season wheat genotype by an average -0.074 day yr(-1) ,
with flowering 'velocity' of up to 0.95 km yr(-1) towards the coastal edges of
the wheatbelt; this is an estimate of how quickly the given genotype would have
to be 'moved' across the landscape to maintain its original flowering time. By
2030, these national changes are projected to accelerate by up to 3-fold for
seasonal temperature and by up to 5-fold for flowering time between now and 2030,
with average national shifts in flowering time of 0.33 and 0.41 day yr(-1)
between baseline and the worst climate scenario tested for 2030 and 2050,
respectively. Without new flowering alleles in commercial germplasm, the life
cycle of wheat crops is predicted to shorten by 2 weeks by 2030 across the
wheatbelt for the most pessimistic climate scenario. While current cultivars may
be otherwise suitable for future conditions, they will flower earlier due to
warmer temperatures. To allow earlier sowing to escape frost, heat and terminal
drought, and to maintain current growing period of early-sown wheat crops in the
future, breeders will need to develop and/or introduce new genetic sources for
later flowering, more so in the eastern part of the wheatbelt.
PMID- 26432667
TI - Cytogenetics in multiple myeloma patients progressing into extramedullary
disease.
AB - BACKGROUND: Extramedullary disease in multiple myeloma patients is an uncommon
event occurring either at the time of diagnosis, or during disease
progression/relapse. This manifestation is frequently associated with poor
outcome and resistance to treatment. We evaluated chromosomal alterations of
plasma cells of multiple myeloma patients with extramedullary relapse, either in
the bone marrow (BM) or at extramedullary sites, and in previous BM collection by
interphase fluorescence in situ hybridization. MATERIAL AND METHODS: Thirty-one
patients [25 BM plasma cells (BMPCs), 18 extramedullary tumor plasma cells], of
which 12 had paired samples of BM and extramedullary plasma cells and 14 had
previous collection of BM, were investigated for the presence of chromosomal
aberrations (CHAs): del(17)(p13), del(13)(q14), 14q32 disruption,
t(4;14)(p16;q32), t(14;16)(q32;q23), gain(1)(q21), and hyperdiploidy status.
RESULTS: Overall, in unrelated samples, t(4;14) was more prevalent in
extramedullary plasma cells, and hyperdiploidy was more frequent in BMPCs. In
paired samples, there was a higher frequency of del(13)(q14) and 14q32 disruption
in BMPCs. Frequency of all studied CHAs was higher in BMPCs of extramedullary
patients than in their previous sample collection. CONCLUSION: These data show
that plasma cells harbor more aberrations during their transformation into
extramedullary form.
PMID- 26432668
TI - Smoothened Regulation: A Tale of Two Signals.
AB - The G protein-coupled receptor (GPCR) Smoothened (Smo) is the signal transducer
of the developmentally and therapeutically relevant Hedgehog (Hh) pathway.
Although recent structural analyses have advanced our understanding of Smo
biology, several questions remain. Chief among them are the identity of its
natural ligand, the regulatory processes controlling its activation, and the
mechanisms by which it signals to downstream effectors. In this review, we
discuss recent discoveries from multiple model systems that have set the stage
for solving these mysteries. We focus on the roles of distinct Smo functional
domains, post-translational modifications, and trafficking, and conclude by
discussing their contributions to signal output.
PMID- 26432669
TI - Obstructive airway in Morquio A syndrome, the past, the present and the future.
AB - Patients with severe tracheal obstruction in Morquio A syndrome are at risk of
dying of sleep apnea and related complications. Tracheal obstruction also leads
to life-threatening complications during anesthesia as a result of the difficulty
in managing the upper airway due to factors inherent to the Morquio A syndrome,
compounded by the difficulty in intubating the trachea. A detailed description of
the obstructive pathology of the trachea is not available in the literature
probably due to lack of a homogenous group of Morquio A patients to study at any
one particular center. We present a series of cases with significant tracheal
obstruction who were unrecognized due to the difficulty in interpreting tracheal
narrowing airway symptoms. Our goal is to provide the guidelines in the
management of these patients that allow earlier recognition and intervention of
tracheal obstruction. Sagittal MRI images of the cervical spine of 28 Morquio A
patients (12+/-8.14years) showed that19/28 (67.9%) patients had at least 25%
tracheal narrowing and that narrowing worsened with age (all 8 patients over
15years had greater than 50% narrowing). Eight out of 28 patients were
categorized as severe (>75%) tracheal narrowing when images were evaluated in
neutral head and neck position. Of the 19 patients with tracheal narrowing,
compression by the tortuous brachiocephalic artery was the most common cause
(n=15). Evidence of such tracheal narrowing was evident as early as at 2years of
age. The etiology of tracheal impingement by the brachiocephalic artery in
Morquio A appears to be due to a combination of the narrow thoracic inlet
crowding structures and the disproportionate growth of trachea and
brachiocephalic artery in relationship to the chest cavity leading to tracheal
tortuosity. In conclusion, tracheal narrowing, often due to impression from the
crossing tortuous brachiocephalic artery, increases with age in Morquio A
patients. Greater attention to the trachea is needed when evaluating cervical
spine MRIs as well as other imaging and clinical investigations, with the goal of
establishing a timely treatment protocol to reduce the mortality rate in this
patient population.
PMID- 26432670
TI - Molecular diagnosis of hypophosphatasia and differential diagnosis by targeted
Next Generation Sequencing.
AB - Hypophosphatasia (HPP) is a rare inherited skeletal dysplasia due to loss of
function mutations in the ALPL gene. The disease is subject to an extremely high
clinical heterogeneity ranging from a perinatal lethal form to
odontohypophosphatasia affecting only teeth. Up to now genetic diagnosis of HPP
is performed by sequencing the ALPL gene by Sanger methodology. Osteogenesis
imperfecta (OI) and campomelic dysplasia (CD) are the main differential diagnoses
of severe HPP, so that in case of negative result for ALPL mutations, OI and CD
genes had often to be analyzed, lengthening the time before diagnosis. We report
here our 18-month experience in testing 46 patients for HPP and differential
diagnosis by targeted NGS and show that this strategy is efficient and useful. We
used an array including ALPL gene, genes of differential diagnosis COL1A1 and
COL1A2 that represent 90% of OI cases, SOX9, responsible for CD, and 8
potentially modifier genes of HPP. Seventeen patients were found to carry a
mutation in one of these genes. Among them, only 10 out of 15 cases referred for
HPP carried a mutation in ALPL and 5 carried a mutation in COL1A1 or COL1A2.
Interestingly, three of these patients were adults with fractures and/or low BMD.
Our results indicate that HPP and OI may be easily misdiagnosed in the prenatal
stage but also in adults with mild symptoms for these diseases.
PMID- 26432672
TI - Lipophilic Statins and Aldosterone Secretion: A Bridge Too Far?
PMID- 26432671
TI - Statin Use and Adrenal Aldosterone Production in Hypertensive and Diabetic
Subjects.
AB - BACKGROUND: Statins substantially reduce cardiovascular mortality and appear to
have beneficial effects independent of their lipid-lowering properties. We
evaluated the hypothesis that statin use may modulate the secretion of
aldosterone, a well-known contributor to cardiovascular disease. METHODS AND
RESULTS: We measured adrenal hormones in 2 intervention studies. In study 1 in
hypertensive subjects, aldosterone was analyzed at baseline and after angiotensin
II stimulation on both high- and low-sodium diets (1122 observations, 15% on
statins for >3 months). Statin users had 33% lower aldosterone levels in adjusted
models (P<0.001). Cortisol was not modified by statins. In secondary analyses,
the lowest aldosterone levels were seen with lipophilic statins and with higher
doses. Statin users had lower blood pressure and reduced salt sensitivity of
blood pressure (both P<0.001). In study 2, aldosterone was measured in diabetic
patients on a high-sodium diet, before and after angiotensin II stimulation (143
observations, 79% statin users). Again, statin users had 26% lower aldosterone
levels (P=0.006), particularly those using lipophilic statins. Ex vivo studies in
rat adrenal glomerulosa cells confirmed that lipophilic statins acutely inhibited
aldosterone, but not corticosterone, in response to different secretagogues.
CONCLUSIONS: Statin use among hypertensive and diabetic subjects was associated
with lower aldosterone secretion in response to angiotensin II and a low-sodium
diet in 2 human intervention studies. This effect appeared to be most pronounced
with lipophilic statins and higher doses. Future studies to evaluate whether
aldosterone inhibition may partially explain the robust cardioprotective effects
of statins are warranted.
PMID- 26432673
TI - The Effect of Implementing a Multimodal Approach on the Rates of Periprosthetic
Joint Infection After Total Joint Arthroplasty.
AB - INTRODUCTION: We examined the efficacy of implementing a multimodal program aimed
at reducing the incidence of periprosthetic joint infection (PJI) after total
joint arthroplasty (TJA) in a mid-size community hospital. METHODS: An infection
reduction committee (IRC) was formed at our hospital in November 2010. The IRC
consisted of two orthopaedic surgeons, an infectious disease specialist, an
internist with extensive experience in perioperative medical management of TJA
patients, an anesthesiologist, the hospital infection control nurse, and two
additional nurses. Their goals were to 1) evaluate the current incidence of PJI
at our institution, compare it with the reported national data, and consider
measures already in place directed at preventing PJI; 2) review and routinely
evaluate recently published studies or information obtained from continuing
medical education events related to PJI to determine if practice changes were
warranted (based on intervention efficacy, cost, and safety) and then develop a
plan to implement appropriate alterations in perioperative protocols using a
multimodal strategy; and 3) evaluate the effect and safety of newly-introduced
infection reduction strategies on the incidence of PJI. RESULTS: In 2008, the
incidence of PJI at our hospital was 1.0%. By 2013, this rate had reduced to
0.4%. In absolute numbers, in 2009, 20 of 1,150 TJAs developed a PJI in the 12
month period following partial, primary, or revision TJA. In 2013, PJI occurred
in only 4 of 1,053 TJA patients. CONCLUSION: We found that formation of an IRC
focused on evaluating and implementing strategies to reduce PJI following TJA can
be effective.
PMID- 26432674
TI - Midterm Outcomes of Revision Total Hip Arthroplasty Using a Modular Revision Hip
System.
AB - BACKGROUND: The growth in hip arthroplasty surgery has meant a corresponding
escalating revision burden with increasing challenges for the orthopaedic
surgeon. The purpose of this study was to review clinical outcomes of a modular
revision hip system within a single institution. METHODS: We retrospectively
reviewed a cohort of modular revision hip system stems performed in our
institution between January 2005 and October 2012 giving a potential minimum
follow-up of 2 years. Clinical outcomes data on complications, Oxford Hip Score
(OHS, 0-48) and patient satisfaction were collected. Radiographic outcomes
including subsidence were assessed. Implant survival was estimated using Kaplan
Meier analysis. RESULTS: 115 stems in 106 patients were identified. All cause
survival was 82% (95%CIs: 73%-89%) at 6.1 years; survival excluding infection
being 99% (95%CIs: 93%-100%). There was a low incidence of subsidence (seven
stems) and no peri-prosthetic fractures. Primary cause of re-revision in this
series was re-infection with only one re-revision for mechanical failure. Median
Oxford Hip Score at mean follow up 4.1 years (2-9) was 40 (14-48) and 93% of
patients reported being satisfied with their revision surgery. CONCLUSION: This
study showed good clinical outcomes and survival using a modular revision stem
with low mechanical failure and subsidence. Recurrence of infection remains a
challenge in revision surgery.
PMID- 26432675
TI - The Risk of a Deep Infection Associated With Intraarticular Injections Before a
Total Knee Arthroplasty.
AB - The aim of the study is to identify the risks associated with an intraarticular
injection before a total knee arthroplasty (TKA). A total of 1628 patients were
retrospectively studied over a 7-year period. The patients were divided into 2
groups: patient who received an intraarticular injection before a TKA and
patients who did not receive an injection before a TKA. There were 16 deep
infections identified (0.98%). Ten deep infections were identified in the
patients who did not receive an injection before a TKA (1.18%), and 6 deep
infections were identified in patients who received an injection before a TKA
(0.77%). There does not appear to be a correlation with the timing of the
injection before surgery and increased risk of infection.
PMID- 26432676
TI - Impact of dynamic changes to a bone metastases pathway in a large, integrated,
National Cancer Institute-designated comprehensive cancer center network.
AB - PURPOSE: Studies suggest equivalent pain relief from bone metastases after
radiation therapy with >10-fraction regimens and shorter courses. Although
American Society for Radiation Oncology evidence-based guidelines and the
Choosing Wisely campaign endorse single-fraction treatments and caution against
the use of extended courses, publications report single-fraction utilization
rates below 5%. We evaluated the impact of our bone metastasis clinical pathway
on the adoption of short-course palliative radiation in a large, integrated
radiation oncology network. METHODS AND MATERIALS: We implemented a clinical
pathway for the management of bone metastases in 2003 that required the entry of
management decisions into an online tool that subjected off-pathway choices to
peer review beginning in 2009. In 2014, the pathway was modified to encourage
single-fraction treatments, and the use of >10 fractions was considered off
pathway. Data were obtained from 16 integrated sites (4 academic, 12 community)
from 2003 through 2014. Multivariate logistic regression was conducted to
establish factors associated with treatment with a single fraction and with >10
fractions. RESULTS: In this study, 12,678 unique courses were delivered. From
2003 to 2008, the single-fraction utilization rate was 7.6%. This increased to
10.9% from 2009 to 2013 and to 15.8% in 2014. The odds ratios for single-fraction
use were 1.59 (95% confidence interval [CI], 1.39-1.81) and 2.58 (95% CI, 2.11
3.15) for 2009-2013 and 2014, respectively. Academic physicians were more likely
to treat with a single fraction (odds ratio, 5.00; 95% CI, 4.38-5.71). Use of >10
fraction regimens significantly decreased from 18.6% in 2003-2008 to 15.2% in
2009-2013 and 9.7% in 2014. CONCLUSIONS: Although our single-fraction utilization
rate was initially in line with national rates (7.6%), the adoption rate
increased to >15%. The use of >10-fraction regimens decreased significantly,
predominantly among community practices. By 2014, >90% of courses were delivered
with <10 fractions. This study demonstrates that provider-driven clinical
pathways are able to standardize practice patterns and promote change consistent
with evidence-based guidelines.
PMID- 26432677
TI - Tomotherapy improves local control and changes failure patterns in locally
advanced malignant pleural mesothelioma.
AB - PURPOSE: The purpose of the study was to determine whether intensity modulated
radiation therapy delivered via helical tomotherapy improves local control (LC)
after pleurectomy/decortication (P/D) for malignant pleural mesothelioma compared
with 3-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS:
Forty-five consecutive patients were treated with adjuvant radiation to 45 Gy in
1.8 Gy fractions after P/D between 2006 and 2014; 23 received 3D-CRT, and 22
received tomotherapy. Kaplan-Meier analysis was used to calculate overall
survival, time to in-field or local failure (LF), and time to out-of-field
failure. The Student t test and Fisher exact test were used to detect between
group differences. RESULTS: Median follow-up time was 19.4 months and 12.7 months
for the 3D-CRT and tomotherapy groups, respectively. Eighty-two percent of
patients had T3/T4 disease, and 64% had positive nodes; 17.4% and 41% of patients
in the 3D-CRT and tomotherapy groups had nonepithelioid histology, respectively.
Mean planning target volume dose, percentage of planning target volume receiving
100% of the prescription dose, and lung doses were significantly greater with
tomotherapy (P < .05), but toxicity rates (including radiation pneumonitis rates)
were equivalent. LC was significantly improved with tomotherapy on Kaplan-Meier
analysis with outcomes censored at 2 years (P < .05); uncensored, this became a
trend (P = .06). Median time to LF was 19 months with tomotherapy and 10.9 months
in 3D-CRT (the latter interval being less than the median follow-up in the
tomotherapy group). On univariate analysis, treatment modality was the only
significant predictor of LC (P < .05). Isolated LF was significantly more
frequent with 3D-CRT (P < .05). Conversely, isolated out-of-field failure was
significantly more frequent with tomotherapy (P < .05). Overall survival and out
of-field control were not significantly different. CONCLUSION: Tomotherapy after
P/D for malignant pleural mesothelioma is associated with improved target
coverage that translates into improved LC compared with 3D-CRT. This is related
to a change in failure patterns, with isolated LF being more common in the 3D-CRT
group and isolated out-of-field failures predominating in the tomotherapy group.
PMID- 26432678
TI - A framework for quality improvement and patient safety education in radiation
oncology residency programs.
AB - In training future radiation oncologists, we must begin to focus on training
future QI specialists. Our patients are demanding better quality and safer care,
and accrediting bodies are requiring it. We must equip radiation oncology
trainees to be leaders in this new world. To that end, a QI/PS educational
program should contain 2 components: a didactic portion focused on teaching basic
QI tools as well as an overview of the quality and safety goals of the
institution, and an experiential component, ideally a resident-led QI project
mentored by an expert faculty member and that is linked to the department's and
institution's goals.
PMID- 26432679
TI - Variability in clinical target volume delineation for intensity modulated
radiation therapy in 3 challenging cervix cancer scenarios.
AB - PURPOSE: The purpose of this study was to assess variability in contouring the
gross tumor volume (GTV) and clinical target volume (CTV) of 3 clinical cervix
cancer cases by a cohort of international experts in the field in preparation for
the development of an online teaching atlas. METHODS AND MATERIALS: Twelve
international experts participated. Three clinical scenarios: node positivity
(PLN), retroverted uterus (RV), and parametrial invasion (PI) were used. Sagittal
and axial magnetic resonance images of the clinical cases were downloaded to
participants' treatment planning systems for contouring. The
GTV/cervix/uterus/parametria/vagina and nodal CTV were contoured. Contour
consensus was assessed for sensitivity/specificity using an expectation
maximization algorithm called Simultaneous Truth and Performance Level Estimation
and experts' overall agreement was summarized by kappa statistics. RESULTS:
Agreement for GTV in the 3 clinical cases was high (Simultaneous Truth and
Performance Level Estimation sensitivity, 0.54-0.92; specificity, 0.97-0.98; and
kappa measure for PLN, RV, and PI was 0.86, 0.76, and 0.42; P < .0001). Moderate
to substantial agreement was seen for nodal CTV (kappa statistics for PLN, RV,
and PI was 0.65, 0.58, and 0.62; P < .0001), uterus (kappa for PLN, RV, and PI
was 0.45, 0.74, and 0.77; P < .0001), and parametria (kappa for PLN, RV, and PI
was 0.49, 0.62, and 0.50; P < .0001). Contouring heterogeneity was greatest for
the cervix (kappa measure for PLN, RV, and PI was 0.15, 0.4, and 0.24; P < .0001)
and vagina (kappa for PLN, RV, and PI was 0.47, 0.36 and 0.46; P < .0001),
reflecting difficulties in determining the interface between GTV and these
tissues. CONCLUSION: Kappa statistics of the different CTV components generally
demonstrated moderate to substantial agreement among international experts in the
field of gynecological radiation therapy. Further planning target volume margins
accounting for organ motion and setup errors are a necessary addition to the CTV.
PMID- 26432680
TI - Clinical and cosmetic outcomes in patients treated with high-dose-rate electronic
brachytherapy for nonmelanoma skin cancer.
AB - PURPOSE: To retrospectively analyze clinical and cosmetic outcomes in patients
treated for nonmelanoma skin cancer (NMSC) with high-dose-rate (HDR) electronic
brachytherapy (EBT) using surface applicators. METHODS AND MATERIALS: We
identified 127 patients who had 154 NMSC lesions, 149 of which were basal cell
carcinoma, treated with HDR EBT at our institution between July 2012 and March
2014. Lesions were treated to 40 Gy in 8 fractions. Local control, acute
toxicity, late toxicity, and cosmetic outcomes were analyzed retrospectively.
Acute and late toxicities were graded using the Common Terminology Criteria for
Adverse Events, version 4.0. Cosmetic outcomes were graded using a standard scale
based on the Radiation Therapy Oncology Group and European Organization for
Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema.
RESULTS: Median (range) follow-up from completion of treatment was 16.1 (3.4-34.8
months). The overall crude recurrence rate was 1.3% (n = 2). Grade 0 to 1 acute
radiation dermatitis was observed in 52.6% of treated lesions (n = 81), grade 2
in 34.4% (n = 53), and grade 3 in 13.0% (n = 20). No acute toxicity greater than
grade 3 was observed and all acute toxic events resolved after treatment. Grade 0
to 1 late toxicity was observed in 94.2% of cases (n = 145), and grade 2 in 5.8%
(n = 9). No late toxicity greater than grade 2 was observed. Across the 152
controlled lesions, cosmetic results were excellent in 94.2% of treated lesions
(n = 145), good in 3.3% (n = 5), fair in 0.7% (n = 1), and poor in 0.7% (n = 1).
CONCLUSIONS: HDR EBT confers promising local control, minimal toxicity, and
excellent cosmesis in our institutional experience. It should be considered ideal
for NMSC of the head and neck, particularly for basal cell carcinoma involving
central facial locations where surgical cosmesis may be inferior.
PMID- 26432681
TI - Can the Neighborhood Built Environment Make a Difference in Children's
Development? Building the Research Agenda to Create Evidence for Place-Based
Children's Policy.
AB - Healthy child development is determined by a combination of physical, social,
family, individual, and environmental factors. Thus far, the majority of child
development research has focused on the influence of individual, family, and
school environments and has largely ignored the neighborhood context despite the
increasing policy interest. Yet given that neighborhoods are the locations where
children spend large periods of time outside of home and school, it is plausible
the physical design of neighborhoods (built environment), including access to
local amenities, can affect child development. The relatively few studies
exploring this relationship support associations between child development and
neighborhood destinations, green spaces, interaction with nature, traffic
exposure, and housing density. These studies emphasize the need to more deeply
understand how child development outcomes might be influenced by the neighborhood
built environment. Pursuing this research space is well aligned with the current
global movements on livable and child-friendly cities. It has direct public
policy impact by informing planning policies across a range of sectors (urban
design and planning, transport, public health, and pediatrics) to implement place
based interventions and initiatives that target children's health and development
at the community level. We argue for the importance of exploring the effect of
the neighborhood built environment on child development as a crucial first step
toward informing urban design principles to help reduce developmental
vulnerability in children and to set optimal child development trajectories
early.
PMID- 26432682
TI - Bacillus thuringiensis impacts on primary and secondary baculovirus transmission
dynamics in Lepidoptera.
AB - Synergistic interactions between entomopathogenic micro-organisms can potentially
be exploited to improve biological control of invertebrate pests but empirical
data at the population level describing multiple-pathogen transmission dynamics
is lacking. We examined how co-inoculation of Bacillus thuringiensis subsp.
kurstaki (Btk) and the baculovirus Panolis flammea nucleopolyhedrovirus (PaflNPV)
in an experimental field population of Lepidopteran Mamestra brassicae larvae
impacted on viral transmission dynamics. We determined how the presence of Btk
influenced primary and secondary PaflNPV transmission. When Btk was co-inoculated
with PaflNPV, there was increased proportional viral mortality in primary
transmission studies compared to plots with virus alone. A delay of up to 4days
between applications of Btk and PaflNPV did not impact on primary viral
mortality, indicating that a lag between inoculations was unlikely to affect the
biocontrol potential of the two pathogens. Viral yields from cadavers in plots
with Btk present were significantly lower than those from plots with virus only,
and secondary cycling to introduced secondary transmission larvae was
significantly reduced. Baculovirus transmission (in terms of the proportion of
uninfected larvae in different treatments) was described by a 'refuge' model that
allowed for heterogeneity in susceptibility and pathogen exposure. We discuss how
transmission may be potentially affected by factors such as host feeding rate,
spatial distribution of virus and interactions between pathogens within the
insect host. This study improves understanding of the impact of pathogens within
host populations and how mixtures of pathogens may be exploited for biocontrol of
insect pests.
PMID- 26432683
TI - The EHR and building the patient's story: A qualitative investigation of how EHR
use obstructs a vital clinical activity.
AB - BACKGROUND: Recent research has suggested that using electronic health records
(EHRs) can negatively impact clinical reasoning (CR) and interprofessional
collaborative practices (ICPs). Understanding the benefits and obstacles that EHR
use introduces into clinical activities is essential for improving medical
documentation, while also supporting CR and ICP. METHODS: This qualitative study
was a longitudinal pre/post investigation of the impact of EHR implementation on
CR and ICP at a large pediatric hospital. We collected data via observations,
interviews, document analysis, and think-aloud/-after sessions. Using
constructivist Grounded Theory's iterative cycles of data collection and
analysis, we identified and explored an emerging theme that clinicians described
as central to their CR and ICP activities: building the patient's story. We
studied how building the patient's story was impacted by the introduction and
implementation of an EHR. RESULTS: Clinicians described the patient's story as a
cognitive awareness and overview understanding of the patient's (1) current
status, (2) relevant history, (3) data patterns that emerged during care, and (4)
the future-oriented care plan. Constructed by consolidating and interpreting a
wide array of patient data, building the patient's story was described as a
vitally important skill that was required to provide patient-centered care,
within an interprofessional team, that safeguards patient safety and clinicians'
professional credibility. Our data revealed that EHR use obstructed clinicians'
ability to build the patient's story by fragmenting data interconnections.
Further, the EHR limited the number and size of free-text spaces available for
narrative notes. This constraint inhibited clinicians' ability to read the why
and how interpretations of clinical activities from other team members. This
resulted in the loss of shared interprofessional understanding of the patient's
story, and the increased time required to build the patient's story. CONCLUSIONS:
We discuss these findings in relation to research on the role of narratives for
enabling CR and ICP. We conclude that EHRs have yet to truly fulfill their
promise to support clinicians in their patient care activities, including the
essential work of building the patient's story.
PMID- 26432684
TI - Is single portal vein approach sufficient for hypothermic machine perfusion of
DCD liver grafts?
PMID- 26432685
TI - Age-dependent changes in extracellular matrix turnover: An under evaluated issue
in the approach to chronic liver diseases.
PMID- 26432686
TI - Microwave-assisted extraction and a new determination method for total steroid
saponins from Dioscorea zingiberensis C.H. Wright.
AB - An efficient microwave-assisted extraction (MAE) technique was applied to isolate
total steroid saponins from Dioscorea zingiberensis C.H. Wright (DZW). The
optimal extracting conditions were established as 75% ethanol as solvent, ratio
of solid/liquid 1:20 (g/ml), temperature 75 degrees C, irradiation power 600 W
and three extraction cycles of 6 min each. Scanning electron microscopy (SEM)
images of DZW processed by four different extractions provided visual evidence of
the disruption effect on DZW. Diosgenin was quantified by HPLC and examined
further by LC-ESI/MS after acid hydrolysis. Total steroid saponins were
calculated using diosgenin from total steroid saponins. The MAE procedure was
optimized, validated and compared with other conventional extraction processes.
This report provides a convenient technology for the extraction and
quantification of total saponins of DZW combining MAE with HPLC and LC-ESI/MS for
the first time.
PMID- 26432687
TI - Crystallographic and spectroscopic study on a known orally active progestin.
AB - 6,17alpha-Dimethyl-4,6-pregnadiene-3,20-dione (medrogestone, 2) is for a long
time known steroid endowed with progestational activity. In order to study its
crystallographic and NMR spectroscopic properties with the aim to fill the
literature gap, we prepared medrogestone following a traditional procedure. A
careful NMR study allowed the complete assignment of the (1)H and (13)C NMR
signals not only of medrogestone but also of its synthetic intermediates. The
structural and stereochemical characterizations of medrogestone together with its
precursor 17alpha-methyl-3-ethoxy-pregna-3,5-dien-20-one were described by means
of X-ray analysis, allowing a deepened conformational investigation.
PMID- 26432688
TI - Epoetin beta pegol prevents endothelial dysfunction as evaluated by flow-mediated
dilation in chronic kidney disease rats.
AB - Chronic kidney disease (CKD) patients have a poor prognosis due to cardiovascular
disease. Anemia and endothelial dysfunction are important risk factors for
cardiovascular events in CKD patients, and treatment with erythropoiesis
stimulating agent (ESA) has been reported to improve the quality of life in CKD
patients. In this study, we evaluated the effect of anemia correcting dose of
epoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.) on
endothelial function in 5/6 nephrectomized rats (Nx rats). C.E.R.A. was
subcutaneously administered once a fortnight, 5 times in total, from 1 week after
nephrectomy. Twenty-four hours after last administration, endothelial function
was evaluated by measuring flow-mediated dilation (FMD) in the femoral arteries
of anesthetized Nx rats by ultrasound system. Femoral arteries were harvested for
western blot analysis. C.E.R.A. significantly increased FMD of Nx rats.
Endothelium-independent vasodilation induced by nitroglycerin injection was not
influenced by C.E.R.A treatment. Nox4 expression and nitrotyrosine accumulation
were significantly decreased, and phosphorylation of eNOS was significantly
enhanced in the femoral arteries of C.E.R.A.-treated rats. C.E.R.A. normalized
hemoglobin levels but did not affect body weight, systolic blood pressure, heart
rate, urinary protein excretion and plasma creatinine. These results indicate
that C.E.R.A. prevented endothelial dysfunction in Nx rats, possibly through
reduction of local oxidative stress and enhancement of eNOS phosphorylation in
the arteries. This study provides the first evidence that C.E.R.A. prevented
endothelial dysfunction in CKD model rats under conditions of amelioration of
anemia.
PMID- 26432689
TI - The effects of caffeic, coumaric and ferulic acids on proliferation, superoxide
production, adhesion and migration of human tumor cells in vitro.
AB - Reactive oxygen species are well-known mediators of various biological responses.
In this study, we examined the effect of three phenolic acids, caffeic, coumaric
and ferulic acids, on superoxide anion production, adhesion and migration of
human lung (A549) and colon adenocarcinoma (HT29-D4) cancer cell lines.
Proliferation of both tumor cells was inhibited by phenolic acids. Caffeic,
coumaric and ferulic acids also significantly inhibited superoxide production in
A549 and HT29-D4 cells. Superoxide anion production decreased by 92% and 77% at
the highest tested concentration (200 uM) of caffeic acid in A549 and HT29-D4
cell lines respectively. Furthermore, A549 and HT29-D4 cell adhesion was reduced
by 77.9% and 79.8% respectively at the higher tested concentration of ferulic
acid (200 uM). Migration assay performed towards A549 cell line, revealed that
tested compounds reduced significantly cell migration. At the highest
concentration tested (200 uM), the covered surface was 7.7%, 9.5% and 35% for
caffeic, coumaric or ferulic acids, respectively. These results demonstrate that
caffeic, coumaric and ferulic acids may participate as active ingredients in
anticancer agents against lung and colon cancer development, at adhesion and
migration steps of tumor progression.
PMID- 26432690
TI - Tailoring in risk communication by linking risk profiles and communication
preferences: The case of speeding of young car drivers.
AB - Speeding is one of the most relevant risk behaviors for serious and fatal
accidents, particularly among young drivers. This study presents a tailoring
strategy for anti-speeding communication. By referring to their motivational
dispositions toward speeding derived from motivational models of health behavior,
young car drivers were segmented into different risk groups. In order to ensure
that risk communication efforts would actually be capable to target these groups,
the linkage between the risk profiles and communication preferences were
explored. The study was conducted on the basis of survey data of 1168 German car
drivers aged between 17 and 24 years. The data reveal four types of risk drivers
significantly differing in their motivational profiles. Moreover, the findings
show significant differences in communication habits and media use between these
risk groups. By linking the risk profiles and communication preferences,
implications for tailoring strategies of road safety communication campaigns are
derived. Promising segmentation and targeting strategies are discussed also
beyond the current case of anti-speeding campaigns.
PMID- 26432691
TI - The Danish High Risk and Resilience Study--VIA 7--a cohort study of 520 7-year
old children born of parents diagnosed with either schizophrenia, bipolar
disorder or neither of these two mental disorders.
AB - BACKGROUND: Severe mental illnesses like schizophrenia and bipolar disorder are
known to be diseases that to some extent, but not entirely can be understood
genetically. The dominating hypothesis is that these disorders should be
understood in a neurodevelopmental perspective where genes and environment as
well as gene-environment-interactions contribute to the risk of developing the
disease. We aim to analyse the influences of genetic risk and environmental
factors in a population of 520 7-year-old children with either 0, 1 or 2 parents
diagnosed with schizophrenia spectrum psychosis or bipolar disorder on mental
health and level of functioning. We hypothesize that a larger proportion of
children growing up with an ill parent will display abnormal or delayed
development, behavioural problems or psychiatric symptoms compared to the healthy
controls. METHODS/DESIGN: We are establishing a cohort of 5207 year old children
and both their parents for a comprehensive investigation with main outcome
measures being neurocognition, behaviour, psychopathology and neuromotor
development of the child. Parents and children are examined with a comprehensive
battery of instruments and are asked for genetic material (saliva or blood) for
genetic analyses. The participants are recruited via Danish registers to ensure
representativity. Data from registers concerning social status, birth
complications, somatic illnesses and hospitalization are included in the
database. Psychological and relational factors like emotional climate in the
family, degree of stimulation and support in the home and attachment style are
also investigated. DISCUSSION: Data collection started January 1, 2013, and is
successfully ongoing. By Aug 2015 424 families are included. About 20% of the
invited families decline to participate, equal for all groups.
PMID- 26432692
TI - Adiponectin, leptin and IL-1 beta in elderly diabetic patients with mild
cognitive impairment.
AB - The aim of the study was to determine the serum levels of adiponectin, leptin and
IL-1 beta in elderly diabetic patients with and without mild cognitive impairment
(MCI) and to examine the associations of these markers with clinical and
cognitive parameters. A biochemical evaluation was performed of 62 seniors with
type 2 diabetes (T2DM) and MCI, and 132 seniors with T2DM but without MCI
(controls). Serum leptin and IL-1 beta levels were higher and adiponectin
concentration was lower in MCI patients than controls. In MCI subjects,
adiponectin level was negatively correlated with leptin, IL-1 beta levels and
BMI. Leptin concentration was correlated with IL-1 beta level. Univariate
logistic regression models revealed that the factors which increased the
likelihood of diagnosis of MCI in elderly patients with T2DM were higher levels
of HbA1c, leptin, IL-1 beta and triglycerides, as well as lower levels of
adiponectin and HDL cholesterol. Similarly, previous CVD, hypertension,
hyperlipidemia, retinopathy, nephropathy, hypoglycemia, longer duration of
diabetes, increased number of co-morbidities, older age, fewer years of formal
education were found to be associated with MCI. The multivariable model indicated
fewer years of formal education, previous CVD, hypertension, increased number of
co-morbidities, higher HbA1c and IL-1 beta levels and lower adiponectin level.
Elderly diabetic patients with MCI have higher levels of leptin and IL-1 beta and
lower levels of adiponectin. Further prospective studies are needed to determine
the role of these markers in the progression to dementia.
PMID- 26432694
TI - Prevalence of exclusively and concomitant pelvic fractures at magnetic resonance
imaging of suspect and occult hip fractures.
AB - Pelvic fractures may occur together with hip fractures as a result of low energy
trauma. It is unclear whether they do require special attention. There are
conflicting results in the literature about the prevalence of both concomitant
hip and pelvic fractures as well as exclusive pelvic fractures. It has been
reported that hip fractures and obturator ring fractures are mutually exclusive.
To retrospectively analyze the prevalence of exclusively pelvic as well as
concomitant hip and pelvic fractures in patients examined with MRI after low
energy trauma in elderly. During 9 years, 316 elderly patients had been examined
with MRI for suspected or occult hip fracture after a fall. A fracture was
diagnosed when MRI showed focal signal abnormalities in the subcortical bone
marrow, with or without disruption of adjacent cortices. One observer reviewed
all studies. A second observer verified all studies with hip fractures. Follow-up
was available for all but two patients that died prior to hip surgery. The
prevalence of concomitant pelvic and femoral neck or trochanteric fractures was
statistically compared using chi-squared test for categorical variables. Hip
fractures were found in 161 (51 %) patients of which 29 (9 %) had concomitant
pelvic fractures. There were exclusively pelvic fractures in 82 (26 %) patients
of which 65 (79 %) were on the traumatized side only. In 73 patients, there were
no fractures. Occult or suspected hip fractures are not infrequently associated
with pelvic fractures. Exclusively pelvic fractures are not uncommon.
PMID- 26432693
TI - Multimorbidity, Depression, and Mortality in Primary Care: Randomized Clinical
Trial of an Evidence-Based Depression Care Management Program on Mortality Risk.
AB - BACKGROUND: Two-thirds of older adults have two or more medical conditions that
often take precedence over depression in primary care. OBJECTIVE: We evaluated
whether evidence-based depression care management would improve the long-term
mortality risk among older adults with increasing levels of medical comorbidity.
DESIGN: Longitudinal analyses of the practice-randomized Prevention of Suicide in
Primary Care Elderly: Collaborative Trial (PROSPECT). Twenty primary care
practices randomized to intervention or usual care. PATIENTS: The sample included
1204 older primary care patients completing the Charlson Comorbidity Index (CCI)
and other interview questions at baseline. INTERVENTION: For 2 years, a
depression care manager worked with primary care physicians to provide algorithm
based care for depression, offering psychotherapy, increasing the antidepressant
dose if indicated, and monitoring symptoms, medication adverse effects, and
treatment adherence. MAIN MEASURES: Depression status based on clinical
interview, CCI to evaluate medical comorbidity, and vital status at 8 years
(National Death Index). KEY RESULTS: In the usual care condition, patients with
the highest levels of medical comorbidity and depression were at increased risk
of mortality over the course of the follow-up compared to depressed patients with
minimal medical comorbidity [hazard ratio 3.02 (95% CI, 1.32 to 8.72)]. In
contrast, in intervention practices, patients with the highest level of medical
comorbidity and depression compared to depressed patients with minimal medical
comorbidity were not at significantly increased risk [hazard ratio 1.73 (95% CI,
0.86 to 3.96)]. Nondepressed patients in intervention and usual care practices
had similar mortality risk. CONCLUSIONS: Depression management mitigated the
combined effect of multimorbidity and depression on mortality. Depression
management should be integral to optimal patient care, not a secondary focus.
PMID- 26432695
TI - Peer learning in the UNSW Medicine program.
AB - BACKGROUND: The UNSW Australia Medicine program explicitly structures peer
learning in program wide mixing of students where students from two adjoining
cohorts complete the same course together, including all learning activities and
assessment. The purpose of this evaluation is to explore the student experience
of peer learning and determine benefits and concerns for junior and senior
students. METHODS: All medical students at UNSW Australia in 2012 (n = 1608) were
invited to complete the Peer Learning Questionnaire consisting of 26 fixed
response items and 2 open-ended items exploring vertical integration and near
peer teaching. Assessment data from vertically integrated and non-vertically
integrated courses were compared for the period 2011-2013. RESULTS: We received
valid responses from 20 % of medical students (n = 328). Eighty percent of
respondents were positive about their experience of vertical integration. Year 1
students reported that second year students provided guidance and reassurance
(87.8 %), whilst year 2 students reported that the senior role helped them to
improve their own understanding, communication and confidence (84 %). Vertical
integration had little effect on examination performance and failure rates.
CONCLUSIONS: This evaluation demonstrates that vertical integration of students
who are one year apart and completing the same course leads to positive outcomes
for the student experience of learning. Students benefit through deeper learning
and the development of leadership qualities within teams. These results are
relevant not only for medical education, but also for other professional higher
education programs.
PMID- 26432696
TI - Preoperative Prevalence of J-Wave Syndrome Electrocardiographic Patterns and
Their Association With Perioperative Cardiac Events.
AB - OBJECTIVE: To evaluate the preoperative prevalence of each type of J-wave
syndrome electrocardiographic pattern and its association with perioperative
cardiac events. DESIGN: Retrospective study. SETTING: Single hospital university
study. PARTICIPANTS: The study evaluated 930 patients who underwent gynecologic,
abdominal, neurosurgical, orthopedic, and urologic surgeries. INTERVENTIONS:
Preoperative standard 12-lead electrocardiogram (ECG) monitoring was performed,
and each type of J-wave syndrome ECG pattern-types 1, 2, and 3 and Brugada
syndrome-type-was evaluated. Incidence of perioperative cardiac events was
investigated up to 1 year postoperatively using an electronic medical record
system. MEASUREMENTS AND MAIN RESULTS: Data from 789 patients were included in
the final study. Of these, 16 patients (2.0%) had J-wave syndrome: 7 patients
(0.9%) had type-1 patterns; 5 patients (0.6%) had type-2 patterns; 2 patients
(0.3%) had type-3 patterns; and 2 patients (0.3%) had Brugada syndrome-type ECG
patterns. A J-point elevation>=0.2 mV, which is considered to be more dangerous,
was found in only 2 patients with Brugada syndrome-type ECG patterns, both of
whom suffered perioperative lethal arrhythmias. CONCLUSION: Patients with J-wave
syndrome ECG patterns, even dangerous patterns, are not necessarily associated
with a higher risk of perioperative cardiac events. However, Brugada syndrome
type ECG patterns should be carefully monitored.
PMID- 26432697
TI - Combined Lung and Liver Transplantation With Extracorporeal Membrane Oxygenation
Instead of Cardiopulmonary Bypass.
PMID- 26432698
TI - Predictors of Failure in Fast-Track Cardiac Surgery.
AB - OBJECTIVES: Fast-track (FT) management of cardiac surgery patients is associated
with early extubation and reduced length of intensive care unit (ICU) stay, with
potential benefit of reduced hospital costs. The authors examined perioperative
factors and their influence on failure of FT and what implications this failure
had. DESIGN: Prospective data collection from all adult cardiac surgeries between
2011 and 2013. SETTING: Single-institution study. PARTICIPANTS: The study
included 2,770 consecutive adult cardiac surgery patients. INTERVENTIONS: All
participants underwent adult cardiac surgeries. Of those, 451 (16.3%) patients
were selected to undergo FT management. MEASUREMENTS AND MAIN RESULTS: Failure of
FT was defined as early (admission to ICU on day of surgery) or late (patients
later admitted to the ICU from the ward). Univariate and multivariate regression
analyses were used to identify which variables predicted FT failure. Of the 451
patients included in this study, 138 (30.6%) failed the FT, with 115 (83.3%)
early failures and 23 (16.7%) late failures. Predictors of failure were reduced
renal function, hypertension, age, EuroSCORE, cardiopulmonary bypass time, first
lactate or base deficit after surgery (all p<0.01), and cross-clamp time
(p<0.05). Multivariate analysis showed that the strongest predictor of failure
was glomerular filtration rate (GFR)<65 mL/min/BSA (sensitivity, 54%;
specificity, 61%; likelihood ratio, 1.39; area under receiver operating
characteristics curve, 0.59; 95% confidence interval, 0.53-0.64). Median length
of hospital stay was longer for the failed group (5 v 7 days, p<0.001). There
were no mortalities in any of the patients selected for FT. CONCLUSIONS: A number
of perioperative factors are associated with failure to FT, the strongest
predictor being GFR. Failure to FT can lead to significantly longer hospital
stay.
PMID- 26432699
TI - Toxic shock syndrome toxin-1, not alpha-toxin, mediated Bundaberg fatalities.
AB - The 1928 Bundaberg disaster is one of the greatest vaccine tragedies in history.
Of 21 children immunized with a diphtheria toxin-antitoxin preparation
contaminated with Staphylococcus aureus, 18 developed life-threatening disease
and 12 died within 48 h. Historically, the deaths have been attributed to alpha
toxin, a secreted cytotoxin produced by most S. aureus strains, yet the ability
of the Bundaberg contaminant microbe to produce the toxin has never been
verified. For the first time, the ability of the original strain to produce alpha
toxin and other virulence factors is investigated. The study investigates the
genetic and regulatory loci mediating alpha-toxin expression by PCR and assesses
production of the cytotoxin in vitro using an erythrocyte haemolysis assay. This
analysis is extended to other secreted virulence factors produced by the strain,
and their sufficiency to cause lethality in New Zealand white rabbits is
determined. Although the strain possesses a wild-type allele for alpha-toxin, it
must have a defective regulatory system, which is responsible for the strain's
minimal alpha-toxin production. The strain encodes and produces staphylococcal
superantigens, including toxic shock syndrome toxin-1 (TSST-1), which is
sufficient to cause lethality in patients. The findings cast doubt on the belief
that alpha-toxin is the major virulence factor responsible for the Bundaberg
fatalities and point to the superantigen TSST-1 as the cause of the disaster.
PMID- 26432700
TI - [Interventions on the spine].
PMID- 26432701
TI - Biochemical insights from population studies with genetics and metabolomics.
AB - Genome-wide association studies with concentrations of hundreds of small
molecules in samples collected from thousands of individuals (mGWAS) access
otherwise inaccessible natural genetic experiments and their influence on the
metabolic capacities of the human body. By sampling the natural metabolic and
genetic variability that is present in the general population, mGWAS identified
over 150 associations between genetic variants and variation in the metabolic
composition of human body fluids. Many of these genetic variants were found to be
located in enzyme or transporter coding genes, whose functions match the
biochemical nature of the associated metabolites. Associations identified by
mGWAS can reveal novel biochemical knowledge, such as the function of
uncharacterized genes, the biochemical identity of small molecules, and the
structure of entire biochemical pathways. Here we review findings of recent mGWAS
and discuss concrete examples of how their results can be interpreted in a
biochemical context. We describe online resources that are available for mining
mGWAS results. In this context, we present two concepts that also find more
general applications in the field of metabolomics: strengthening of associations
by looking at ratios between metabolite pairs and reconstruction of metabolic
pathways by Gaussian graphical modeling.
PMID- 26432702
TI - Stepping Into and Out of the Void: Funding Dynamics of Human Embryonic Stem Cell
Research in California, Sweden, and South Korea.
AB - Nonprofit organizations and philanthropists stepped into a funding void caused by
controversies over public funding of human embryonic stem cell (hESC) research.
Based on interviews of 83 representatives of 53 funders, we examine the
motivations and accountability structures of public agencies, corporations,
fundraising dependent nonprofit organizations and philanthropic organizations
that funded hESC research in three jurisdictions: California, Sweden, and South
Korea. While non-traditional forms of funding are essential in the early stages
of research advancement, they are unreliable for the long timeframes necessary to
advance cell therapies. Such funding sources may enter the field based on high
expectations, but may exit just as rapidly based on disappointing rates of
progress.
PMID- 26432703
TI - Erratum to: Oxidative Stress and Adult Neurogenesis.
PMID- 26432704
TI - Dissecting the taxonomic heterogeneity within Propionibacterium acnes: proposal
for Propionibacterium acnes subsp. acnes subsp. nov. and Propionibacterium acnes
subsp. elongatum subsp. nov.
AB - Propionibacterium acnes subsp. acnes subsp. nov. and Propionibacterium acnes
subsp. elongatum subsp. nov. are described. These emanate from the three known
phylotypes of P. acnes, designated types I, II and III. Electron microscopy
confirmed the filamentous cell shape of type III, showing a striking difference
from types I/II, which were short rods. Biochemical tests indicated that, in
types I/II, either the pyruvate, l-pyrrolidonyl arylamidase or d-ribose 2 test
was positive, whereas all of these were negative among type III strains. Matrix
assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
MS) spectra, which profile mainly their ribosomal proteins, were different
between these two groups. Surface-enhanced laser-desorption/ionization time-of
flight mass spectrometry (SELDI-TOF MS) spectra of all phylotypes revealed a
specific protein biomarker that was overexpressed in type III strains compared
with types I/II only when grown aerobically. Reference strains had high whole
genome similarity between types I (>91 %) and II (>75 %), but a considerably
lower level of 72 % similarity with type III. recA and gyrB sequence dendrograms
confirmed the distant relatedness of type III, indicating the presence of two
distinct centres of variation within the species P. acnes. On the other hand,
cellular fatty acid profiles and 16S rRNA gene sequence relatedness (>99.3 %)
circumscribed the species. Thus, we propose two subspecies, Propionibacterium
acnes subsp. acnes subsp. nov. for types I/II and Propionibacterium acnes subsp.
elongatum subsp. nov. for type III. The type strain of Propionibacterium acnes
subsp. acnes is NCTC 737T ( = ATCC 6919T = JCM 6425T = DSM 1897T = CCUG 1794T),
while the type strain of Propionibacterium acnes subsp. elongatum is K124T ( =
NCTC 13655T = JCM 18919T).
PMID- 26432705
TI - Laparoscopic versus open peritoneal dialysis catheter insertion for the
management of pediatric acute kidney injury.
AB - BACKGROUND: Acute pediatric dialysis is provided by a single center in New
Zealand. Most acute dialysis in our center is performed in the under 5 age group.
The advantage of using peritoneal dialysis (PD) in these children is the ability
to perform continuous renal replacement therapy without always requiring an ICU
setting, avoiding central venous access and promoting greater cardiovascular
stability. The disadvantage of PD in the acute setting includes the requirement
for immediate use and the potential for early leaks due to peritoneal disruption
with resulting delayed use and restricted volumes. There is a growing trend
toward minimally invasive surgery and the laparoscopic method allows this.
Surgeons at this center have been using a laparoscopic technique since 2005.
METHODS: We performed a 10-year review of acute PD at the Starship Hospital from
2003 to 2013. Data on 102 children who met the criteria were collected. RESULTS:
These 102 children had 113 acute PD catheters. The two groups were comparable in
terms of age and reason for presentation. The median age of the laparoscopic
group was 2 years (interquartile range [IQR] 6) and the open group was 3 years
(IQR 3.2). The predominant diagnosis for both groups was hemolytic uremic
syndrome (HUS) accounting for 71% of laparoscopic cases, and 72% of open cases.
The incidence of infection was 0% versus 7% in the laparoscopic versus open
approach. Ten percent of patients required further manipulation of the catheter
after initial insertion in the laparoscopic group, compared with 11% in the open
approach. Conversion to hemodialysis (HD) due to catheter-related complications
was seen in 10% of laparoscopic cases and 9% of the open cases. Dialysate fluid
leak was noted in 26% in the laparoscopic group compared with 11% in the open
group (p = 0.08). Anesthesia time is longer in the laparoscopic group (p =
0.008). CONCLUSION: We found no significant differences in complication rates
between laparoscopic and open surgical approaches regarding acute PD catheter
insertion. We saw a trend in increased leakage with laparoscopic procedures and a
significantly longer operative time. We concluded that the laparoscopic approach
in the acute situation for emergency dialysis is safe and effective.
PMID- 26432706
TI - Effect of cholecalciferol on local arterial stiffness and endothelial dysfunction
in children with chronic kidney disease.
AB - BACKGROUND: As cardiovascular factors are the leading cause of mortality in
chronic kidney disease (CKD) and as vitamin D deficiency is prevalent in this
population, we aimed to examine the effect of oral cholecalciferol on cardiac
parameters and biomarkers for endothelial cell activation in children with CKD.
METHODS: Forty-one children with CKD and 24 healthy subjects free of any
underlying cardiac or renal disease with low 25-hydroxyvitamin D3 (25OHD) levels
were evaluated using echocardiography basally and following Stoss vitamin D
supplementation. The local vascular stiffness and endothelial dysfunction markers
were compared among the groups. RESULTS: Initial flow-mediated dilatation (FMD)
measurements were lower and local arterial stiffness was significantly higher in
patients. After vitamin D supplementation, these improved significantly in
patients, while no significant change was observed for the healthy group.
Homocysteine showed inverse correlation with baseline vitamin D level in CKD
children and von Willebrand factor emerged as an independent risk factor for FMD
impairment. CONCLUSIONS: Our interventional study revealed the favorable effects
of high-dose cholecalciferol on cardiovascular and endothelial parameters,
implying the importance of vitamin D supplementation in children with CKD.
PMID- 26432707
TI - Characterisation and cytotoxic screening of metal oxide nanoparticles putative of
interest to oral healthcare formulations in non-keratinised human oral mucosa
cells in vitro.
AB - Nanoparticles are increasingly being utilised in the innovation of consumer
product formulations to improve their characteristics; however, established links
between their properties, dose and cytotoxicity are not well defined. The purpose
of this study was to screen four different nanomaterials of interest to oral care
product development in the absence of stabilisers, alongside their respective
bulk equivalents, within a non-keratinised oral epithelial cell model (H376).
Particle morphology and size were characterised using scanning electron
microscopy (SEM) and dynamic light scattering (DLS). The H376 model showed that
zinc oxide (ZnO) was the most cytotoxic material at concentrations exceeding
0.031% w/v, as assessed using the lactate dehydrogenase (LDH) and
dimethylthiazolyl-diphenyl-tetrazolium-bromide (MTT) assays. ZnO cytotoxicity
does not appear to be dependent upon size of the particle; a result supported by
SEM of cell-particle interactions. Differences in cytotoxicity were observed
between the bulk and nanomaterial forms of hydroxyapatite and silica (SiO2);
titanium dioxide (TiO2) was well tolerated in both forms at the doses tested.
Overall, nano-size effects have some impact on the cytotoxicity of a material;
however, these may not be as significant as chemical composition or surface
properties. Our data highlights the complexities involved at the nano-scale, in
both the characterisation of materials and in relation to cytotoxic properties
exerted on oral epithelial cells.
PMID- 26432708
TI - Cystic Endosalpingiosis or Multicystic Mesothelioma?
PMID- 26432709
TI - Response: Cystic Endosalpingiosis or Multicystic Mesothelioma?
PMID- 26432710
TI - Power Morcellator Features Affecting Tissue Spill in Gynecologic Laparoscopy: An
In-Vitro Study.
AB - STUDY OBJECTIVE: To assess features of power morcellators (blade diameter,
circular vs oscillating cutting, blade rotation speed, experience level)
regarding their effect on the amount of tissue spill. In addition, the amount of
tissue spill after the initial two-thirds and final one-third of the morcellated
specimen was evaluated. DESIGN: In vitro study (Canadian Task Force
classification II-2). SETTING: Laparoscopic skills lab of an academic hospital.
PATIENTS: Not applicable. INTERVENTION: Power morcellation of beef tongue
specimens. MEASUREMENTS AND MAIN RESULTS: Twenty-four trials were performed.
Morcellation was performed in 2 phases (phase 1: initial two-thirds of the total
tissue; phase 2: last one-third of the tissue). With larger blade diameter a
decline was observed in both the weight of the spilled particles (phase 1) and
the number of spilled particles (phases 1 and 2 and both combined) (weight phase
1: 6.5 g vs 6.3 g vs 2.2 g for 12.5 mm vs 15 mm vs 20 mm, respectively, p = .04;
number particles: phase 1, 10.2 vs 7.2 vs 2.7, p = .01; phase 2, 22.9 vs 19.0 vs
8.9, p = .02; total, 34.7 vs 26.2 vs 11.6, p = .01). Also, spinning of the tissue
mass due to torque applied by the rotating blade occurred later when blade size
increased, and the size of the spilled particles was larger (weight of
morcellated tissue at onset of torque: 136 g vs 198 g vs 222 g, p = .07; size: .6
g vs .9 g vs .8 g, p = .1). In the oscillation mode there was less total spill
(6.8 g/100 g vs 21.3 g/100 g, p = .01, for oscillation and circular cutting,
respectively). CONCLUSION: The present study demonstrates that less spill is
created by power morcellators with an oscillating blade and/or a large diameter
(>=20 mm). Furthermore, when using a large-diameter blade the spilled particles
are larger, and less morcellation repetitions are needed. By combining these
features with currently introduced contained morcellation, the safety of the
morcellation process with respect to tissue spill can be further improved.
PMID- 26432711
TI - Characteristics of elastofibroma dorsi on PET/CT imaging with (18)F-FDG.
AB - PURPOSE: To assess the characteristics of 18F-FDG uptake in elastofibroma dorsi
(EFD). METHODS: Seventeen patients with EFD were retrospectively studied.
RESULTS: The mean+/-S.D. of SUV was 2.29+/-0.60 (range, 1.2-4.3), and the uptake
were Grade 0 in 6, Grade 1 in 12, Grade 2 in 7, and Grade 3 in 1. There is no
correlation between lesion volume, SUVmax, and computer tomography value. All EFD
lesions showed soft tissue density with low or moderate diffused and homogeneous
uptake of 18F-FDG. CONCLUSIONS: Mild and moderate uptake of 18F-FDG is frequently
observed in EFD, which should be known to avoid making wrong diagnosis.
PMID- 26432713
TI - Severe peripheral neuropathy following carfilzomib, rituximab, and dexamethasone
for initial treatment of Waldenstrom's macroglobulinemia.
PMID- 26432712
TI - [Update peripheral arterial occlusive disease].
AB - Due to demographic changes, peripheral arterial occlusive disease (PAD) has
become one of the most prevalent diseases in western industrial nations. In
recent years the trend towards initial endovascular treatment approaches has
further continued. Because of the high primary success and low complication
rates, intervention-based revascularization strategies are the method of choice
in the majority of cases. The treatment strategy should always be assessed in a
multidisciplinary setting and if possible, within a designated vascular center.
One of the main limitations of interventions is the occurrence of restenosis, in
particular in infrapopliteal arterial lesions. A major progress arose from drug
eluting balloons, which dramatically reduced restenosis rates particular for
femoropopliteal lesions. A potential alternative strategy could be the use of a
combination therapy, such as plaque removal followed by insertion of drug-eluting
balloons; however, economic issues have to be kept in mind for such approaches.
PMID- 26432714
TI - Comparing perceptual and preferential decision making.
AB - Perceptual and preferential decision making have been studied largely in
isolation. Perceptual decisions are considered to be at a non-deliberative
cognitive level and have an outside criterion that defines the quality of
decisions. Preferential decisions are considered to be at a higher cognitive
level and the quality of decisions depend on the decision maker's subjective
goals. Besides these crucial differences, both types of decisions also have in
common that uncertain information about the choice situation has to be processed
before a decision can be made. The present work aims to acknowledge the
commonalities of both types of decision making to lay bare the crucial
differences. For this aim we examine perceptual and preferential decisions with a
novel choice paradigm that uses the identical stimulus material for both types of
decisions. This paradigm allows us to model the decisions and response times of
both types of decisions with the same sequential sampling model, the drift
diffusion model. The results illustrate that the different incentive structure in
both types of tasks changes people's behavior so that they process information
more efficiently and respond more cautiously in the perceptual as compared to the
preferential task. These findings set out a perspective for further integration
of perceptual and preferential decision making in a single ramework.
PMID- 26432716
TI - Discussion.
PMID- 26432715
TI - Is limiting transfusion safe? The devil is in the details.
PMID- 26432717
TI - The impact of 6 weeks of atrial fibrillation on left atrial and ventricular
structure and function.
AB - OBJECTIVE: The impact of prolonged episodes of atrial fibrillation on atrial and
ventricular function has been incompletely characterized. The purpose of this
study was to investigate the influence of atrial fibrillation on left atrial and
ventricular function in a rapid paced porcine model of atrial fibrillation.
METHODS: A control group of pigs (group 1, n = 8) underwent left atrial and left
ventricular conductance catheter studies and fibrosis analysis. A second group
(group 2, n = 8) received a baseline cardiac magnetic resonance imaging to
characterize left atrial and left ventricular function. The atria were rapidly
paced into atrial fibrillation for 6 weeks followed by cardioversion and cardiac
magnetic resonance imaging. RESULTS: After 6 weeks of atrial fibrillation, left
atrial contractility defined by atrial end-systolic pressure-volume relationship
slope was significantly lower in group 2 than in group 1 (1.1 +/- 0.5 vs 1.7 +/-
1.0; P = .041), whereas compliance from the end-diastolic pressure-volume
relationship was unchanged (1.5 +/- 0.9 vs 1.6 +/- 1.3; P = .733). Compared with
baseline, atrial fibrillation resulted in a significantly higher contribution of
left atrial reservoir volume to stroke volume (32% vs 17%; P = .005) and lower
left atrial booster pump volume contribution to stroke volume (19% vs 28%; P =
.029). Atrial fibrillation also significantly increased maximum left atrial
volume (206 +/- 41 mL vs 90 +/- 21 mL; P < .001). Left atrial fibrosis in group 2
was significantly higher than in group 1. Atrial fibrillation decreased left
ventricular ejection fraction (29% +/- 9% vs 58 +/- 8%; P < .001), but left
ventricular stroke volume was unchanged. CONCLUSIONS: In a chronic model of
atrial fibrillation, the left atrium demonstrated significant structural
remodeling and decreased contractility. These data suggest that early
intervention in patients with persistent atrial fibrillation might mitigate
against adverse atrial and ventricular structural remodeling.
PMID- 26432718
TI - Expert opinion is often hot air: It is not the air; it is the clinical evidence.
PMID- 26432719
TI - Late outcomes after the Cox maze IV procedure for atrial fibrillation.
AB - OBJECTIVE: The Cox maze IV procedure (CMPIV) has been established as the gold
standard for surgical ablation; however, late outcomes using current consensus
definitions of treatment failure have not been well described. To compare to
reported outcomes of catheter-based ablation, we report our institutional
outcomes of patients who underwent a left-sided or biatrial CMPIV at 5 years of
follow-up. METHODS: Between January 2002 and September 2014, data were collected
prospectively on 576 patients with AF who underwent a CMPIV (n = 532) or left
sided CMPIV (n = 44). Perioperative variables and long-term freedom from AF, with
and without AADs, were compared in multiple subgroups. RESULTS: Follow-up at any
time point was 89%. At 5 years, overall freedom from AF was 93 of 119 (78%), and
freedom from AF off AADs was 77 of 177 (66%). No differences were found in
freedom from AF, with or without AADs, at 1, 2, 3, 4, and 5 years for patients
with paroxysmal AF (n = 204) versus with persistent/longstanding persistent AF (n
= 305), or for those who underwent standalone versus a concomitant CMP. Duration
of preoperative AF and hospital length of stay were the best predictors of
failure at 5 years. CONCLUSIONS: The outcomes of the CMPIV remain good at late
follow-up. The type of preoperative AF or the addition of a concomitant procedure
did not affect late success. The results of the CMPIV remain superior to those
reported for catheter ablation and other forms of surgical AF ablation,
especially for patients with persistent or longstanding AF.
PMID- 26432720
TI - Large clinical databases for the study of lung cancer: Making up for the failure
of randomized trials.
PMID- 26432721
TI - One-year clinical and angiographic results of hybrid coronary revascularization.
AB - OBJECTIVE: To evaluate 1-year clinical and angiographic results after hybrid
coronary revascularization (HCR) combining off-pump left internal mammary artery
(LIMA) grafting through an inferior J-hemisternotomy with percutaneous coronary
intervention (PCI). METHODS: Prospective, single-arm clinical feasibility study
including 100 consecutive patients with multivessel disease undergoing staged
HCR. The primary endpoint was the major adverse cardiac and cerebrovascular event
rate at 1 year. Secondary endpoints included 1-year all-cause death, stroke,
myocardial infarction, repeat revascularization, and angiographic graft and stent
patency. RESULTS: One-year clinical follow-up data were available in all
patients. The primary endpoint was met by 20 patients (20%). Individual endpoints
were as follows: 1 death due to heart failure; 1 stroke, 2 procedure-related
myocardial infarctions; and 1 spontaneous myocardial infarction during follow-up.
A total of 16 patients underwent repeat revascularization: 5 surgical
reinterventions during the index hospitalization for angiographically suspected
internal mammary artery graft dysfunction, and 3 repeat PCIs. Only 1 patient had
evidence of ischemia. After discharge, PCI was performed in 6 patients who had
recurrent angina, and in 2 asymptomatic patients who had angiographic restenosis.
At the 1-year angiographic follow-up, 87 of 89 (98%) patients had patent internal
mammary artery grafts. Angiographic restenosis was present in 10 of 100 lesions
treated by PCI. CONCLUSIONS: Angiographically controlled HCR was associated with
a high repeat revascularization rate. The 1-year 98% LIMA-graft patency rate, and
low risk of death and stroke, seem promising for the long-term outcome. Non-left
anterior descending coronary artery lesion revascularization remains a challenge.
PMID- 26432722
TI - Minimally invasive mitral valve surgery is associated with equivalent cost and
shorter hospital stay when compared with traditional sternotomy.
AB - OBJECTIVE: Mitral valve surgery is increasingly performed through minimally
invasive approaches. There are limited data regarding the cost of minimally
invasive mitral valve surgery. Moreover, there are no data on the specific costs
associated with mitral valve surgery. We undertook this study to compare the
costs (total and subcomponent) of minimally invasive mitral valve surgery
relative to traditional sternotomy. METHODS: All isolated mitral valve repairs
performed in our health system from March 2012 through September 2013 were
analyzed. To ensure like sets of patients, only those patients who underwent
isolated mitral valve repairs with preoperative Society of Thoracic Surgeons
scores of less than 4 were included in this study. A total of 159 patients were
identified (sternotomy, 68; mini, 91). Total incurred direct cost was obtained
from hospital financial records. RESULTS: Analysis demonstrated no difference in
total cost (operative and postoperative) of mitral valve repair between mini and
sternotomy ($25,515 +/- $7598 vs $26,049 +/- $11,737; P = .74). Operative costs
were higher for the mini cohort, whereas postoperative costs were significantly
lower. Postoperative intensive care unit and total hospital stays were both
significantly shorter for the mini cohort. There were no differences in
postoperative complications or survival between groups. CONCLUSIONS: Minimally
invasive mitral valve surgery can be performed with overall equivalent cost and
shorter hospital stay relative to traditional sternotomy. There is greater
operative cost associated with minimally invasive mitral valve surgery that is
offset by shorter intensive care unit and hospital stays.
PMID- 26432724
TI - Respect for nursing professional: silence must be heard.
AB - The value of care giving seems to be at an all-time low. whether it is clinical
(bedside) or for children and elderly at home (homemakers). Currently,
individuals who pass away any opportunity (for themselves) to care for another
individual instead are considered weak and/or unmotivated. Thus, it is not
surprising that modern society often fails to respect the nursing professionals
to the extent of underplaying their strengths, skills, and even clinical
abilities. While qualities such as kindness, team spirit, and willingness to get
their hands dirty are the core of this profession, nursing professionals have a
complex variety of set duties, involving drug dosage, trouble-shooting, ongoing
patient monitoring, and providing holistic comfort and support to the sick and
needy. Beyond classical role, the nursing professional has currently ventured
into other roles as well, as a nurse practitioner, administrator, researcher, or
even an educator. Thus, considering the wide spectrum of duties performed by
nursing professionals, they do deserve more status and power rather than be
treated like "ward housewives."
PMID- 26432725
TI - Subvalvular disease in patients undergoing balloon mitral valvotomy: a strong
base is not always good.
PMID- 26432723
TI - Signaling pathway and dysregulation of PD1 and its ligands in lymphoid
malignancies.
AB - Tumor cells evade immune destruction, at least partially, by upregulating
inhibitory signals to limit effector T cell activation. Programmed death 1 (PD-1)
is one of the most critical co-inhibitory molecules limiting the T-cell antitumor
response. PD-1 and its ligands, PD-L1 and PD-L2, are overexpressed by various
types of tumors as well as reactive cells in the tumor microenvironment. A
growing body of evidence has shown the clinical efficiency and minimal toxicity
of PD-1 pathway inhibitors in patients with solid tumors, but the role of these
inhibitors in lymphoid malignancies is much less well studied. In this review, we
analyze the pathologic role of the PD-1 pathway in most common lymphoid
malignancies and we organize the clinical data from clinical trials of PD-1
pathway inhibitors. Several anti-PD-1 regimens have shown encouraging therapeutic
effects in patients with relapsed or refractory Hodgkin lymphoma, follicular
lymphoma, and diffuse large B-cell lymphoma. Additional progress is needed to
foster an improved understanding of the role of anti-PD-1 therapy in
reconstituting antitumor immunity in patients with lymphoid malignancies.
Upcoming trials will explore the clinical efficiency of combining PD-1 pathway
inhibitors and various agents with diverse mechanisms of action and create more
therapeutic possibilities for afflicted patients.
PMID- 26432727
TI - Doctors at cross road.
PMID- 26432726
TI - LDL cholesterol, statins and PCSK 9 inhibitors.
AB - Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance
for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statin is
the most effective therapy today to lower LDLc by inhibiting HMG-CoA-reductase.
However despite intensive statin therapy, there remains a residual risk of
recurrent myocardial infarction in about 20-30% cases. Moreover a few patients
develop statin intolerance. For severe hypercholesterolemia, statins alone or in
combination of ezetimibe, niacin and fenofibrate have been advocated. For
homozygous familial hypercholesterolemia (HOFH), a microsomal triglyceride
transfer protein MTP inhibitor (Lopitamide) and antisense oligonucleotide (ASO)
(Mipomersen) have recently been approved by FDA, USA through 'Risk evaluation and
Mitigation Strategy (REMS)'. Possible future therapies include PCSK-9 inhibitors
which have excellent lipid lowering properties. Three monoclonal antibodies (PCSK
9 Inhibitors) alirocumab, evolocumab and Bococizumab are under advanced clinical
stage IV trials and awaiting approval by FDA and European Medicines Agency.
PMID- 26432728
TI - Rejuvenating practice of medicine.
PMID- 26432729
TI - Subvalvular apparatus and adverse outcome of balloon valvotomy in rheumatic
mitral stenosis.
AB - BACKGROUND: Balloon mitral valvotomy (BMV) is a well-established therapeutic
modality for rheumatic mitral stenosis (RMS). However, there are chances of
procedural failure and the more ominous post-procedural severe mitral
regurgitation. There are only a few prospective studies, which have evaluated the
pathogenic mechanisms for these major complications of BMV, especially in
relation to the subvalvular apparatus (SVA) pathology. METHODS: All symptomatic
patients of RMS suitable for BMV by echocardiographic criteria in a span of 1
year were selected. In addition to the standard echocardiographic assessment of
RMS (Wilkins score and score by Padial et al.), a separate grading and scoring
system was assigned to evaluate the severity of the SVA pathology. The SVA score
was 'I', when none of the two SVAs had severe disease, 'II' when one of the two
SVAs has severe disease, and 'III' when both SVAs had severe disease. With these
scoring systems, the outcomes of BMV (successful procedure, failure, and post
procedural mitral regurgitation) were analyzed. Emergency valve replacement was
performed depending on clinical situation, and in cases of replacement, the
pathology of the excised mitral valves were compared with echocardiographic
findings. RESULTS: Of the 356 BMVs performed in a year, 43 patients had adverse
outcomes in the form of failed procedure (14 patients) and mitral regurgitation
(29 patients). Forty-one among these had a SVA score of III. The sensitivity and
specificity of the MR score was lesser than the SVA score (sensitivity 0.34 vs.
1.00, specificity 0.92 vs. 0.99, respectively). The mitral valvular morphology in
39 patients who underwent post-procedural valve replacements correlated well with
echocardiography findings. CONCLUSION: It is important to assess the degree of
SVA pathology in the conventional echocardiographic assessment for RMS, as BMV
would have adverse events when both SVAs were severely diseased.
PMID- 26432730
TI - Association of ST elevation with apical aneurysm in hypertrophic cardiomyopathy.
AB - OBJECTIVES: Apical aneurysms in patients with hypertrophic cardiomyopathy (HCM)
represent an underrecognized but clinically important subset of HCM patients.
However it may be frequently missed by echocardiography because of poor image
quality of left ventricular apex. We aimed to compare electrocardiographic STE in
HCM patients with and without apical aneurysm. METHODS: We developed this
clinical review using an extensive MEDLINE review of the literature and data from
our laboratories; and some electrocardiographic parameters including STE were
analysed in HCM patients with and without apical aneurysm. RESULTS: There were 29
HCM patients without apical aneurysm (Group 1; 52.6+/-17.7years, 69% male) and 28
HCM patients with apical aneurysm (Group 2; 59.6+/-13.2years, 57% male). The STE
in V4-6 derivations were statistically more frequent in patients with apical
aneurysm compared to those without aneurysm (93% vs 7%, p<0.001). There was a
positive correlation between the presence of the STE in V4-6 derivations and the
presence of the apical aneurysm (Spearman's rho=0.895, p<0.001). CONCLUSIONS:
Clinicians and specifically echocardiographers must pay special attention on the
electrocardiography to correctly detect the frequently overlooked apical aneurysm
in HCM patients, and should be careful for apical aneurysm particularly in the
presence of STE in V4-6 derivations.
PMID- 26432731
TI - Periprocedural plasma fibrinogen levels and coronary stent outcome.
AB - AIM: Percutaneous intervention is one of the treatment option for coronary artery
disease. Reinfarction and restenosis is one of the complication of the procedure.
So this study was conducted to assess plasma fibrinogen levels pre- and post
coronary stenting and its relation with outcome. METHODS: After obtaining
informed consent, venous blood samples were collected at three timed points in
relation to stenting - 24h before, 24h after and 72h after stenting to assess
fibrinogen levels. Patients were followed up for six months. Repeat
revascularization, myocardial infarction and symptomatic angina were considered
as major adverse clinical events. RESULTS: 57 patients who underwent successful
stenting and followed up for six months up were included in the study. Mean age
was 53 years and 87.7% were males and 29.8% were diabetics. Baseline plasma
fibrinogen level was significantly high in patients who developed repeat angina
and myocardial infarction after the stenting [288.64+/-59.43 vs 393.75+/
32.97mg/dL, p=0.003] and it remained high during serial assessment [322.74+/
63.92 vs 422.00+/-55.28mg/dL, 326.23+/-65.81 vs 419.50+/-45.82mg/dL, 0.008, 0.012
respectively]. Patients who developed adverse events denied any drug default.
CONCLUSION: We conclude that plasma fibrinogen plays a significant role in the
development of adverse events following stenting shown by high level of plasma
fibrinogen in patients who developed adverse events.
PMID- 26432734
TI - Device closure of pulmonary arteriovenous malformation using Amplatzer vascular
plug II in hereditary hemorrhagic telangiectasia.
AB - Pulmonary arteriovenous malformations (AVM) are very rare and carry the risk of
cerebral thrombo-embolism, brain abscess or pulmonary hemorrhage. The Amplatzer
vascular plug II (AVP II) is a new device, used for embolization of the pulmonary
AVMs. We report a case of pulmonary AVM successfully managed by using AVP II in a
patient with hereditary hemorrhagic telangiectasia (HHT).
PMID- 26432732
TI - Do circulating blood cell types correlate with modifiable risk factors and
outcomes in patients with acute coronary syndrome (ACS)?
AB - AIMS: Atherosclerosis is an inflammatory process with different cardiovascular
risk factors (CVRFs) contributing to its pathogenesis. We aimed to evaluate the
specific relationship between circulating blood leukocytes, troponin I and CVRFs.
METHODS: We prospectively enrolled 959 patients with evidence of acute coronary
syndrome either in form of unstable angina or STEMI or NSTEMI. Details
demographic characteristics, CVRF and biochemical parameters such as total white
blood cells (WBC), neutrophil, lymphocytes, platelet, neutrophil/lymphocyte ratio
(NLR), platelet/lymphocyte ratio (PLR), and troponin I were collected. RESULTS:
The results indicated that patients having either hypertension, diabetes or
smoking habit had significantly higher levels of total WBC (p=0.013), neutrophil
(p=0.029), NLR (p=0.029) and PLR (p=0.009). The level of troponin I was
unaffected by these risk factors. Significant association of hypertension was
found with total WBC (p=0.0392), lymphocytes (p=0.0384) and PLR (p=0.0027),
whereas in diabetes and females all other leukocyte subtypes were significantly
altered except for platelet and troponin I. Smokers had higher level of total WBC
count (p=0.0033) and PLR (p=0.0464). No relationship between CVRFs and leukocytes
was observed in males. The age independent effect was observed with PLR, whereas
association with total WBC, lymphocytes, NLR, platelet was specific in older
population. In younger patients NLR (p=0.0453) is more likely to be elevated.
Mortality was significantly associated with changes in the leukocytes but not
with the CVRF presence. CONCLUSION: We demonstrate that the neutrophils,
lymphocytes and total WBC along with its ratios predict mortality and are more
likely to be elevated in presence of CVRFs.
PMID- 26432733
TI - Inadvertent transarterial pacemaker lead placement.
AB - We present a case of a 73-year-old patient with acute left-sided hemiparesis four
months after right ventricular pacemaker insertion. Post-procedural
electrocardiogram revealed a paced RBBB complex and an abnormal lead path on
chest X-ray. Subsequent echocardiography and computed tomography showed left
ventricular pacemaker malposition with retrograde passage to the punctured
subclavian artery. We also discuss the utility of routine cardiac investigations
post-insertion to identify signal lead malposition as well as management
strategies once identified.
PMID- 26432735
TI - Isolated quadricuspid aortic valve referred with diagnosis of rheumatic carditis.
AB - Quadricuspid aortic valve is a rare congenital malformation of the aortic valve.
It appears often isolated or sometimes associated with other truncal anomalies,
and approximately 50% of patients have aortic regurgitation. In this article we
reported an eight-years-old boy referred with diagnose of rheumatic carditis from
the outer medical center.
PMID- 26432736
TI - Use of ADO II device in a large aorto-pulmonary collateral -an interesting case.
AB - A 11month old girl was diagnosed to have a large aorto pulmonary collateral
during evaluation for respiratory distress and seizures. Echocardiographic
evaluation showed a large collateral from the descending aorta to left lung with
ventricular dysfunction (left ventricular ejection fraction of 40%). This was
confirmed on computed tomography angiogram (CT) scan. The collateral was closed
with Amplatzer Ductal Occluder II device under fluoroscopic guidance. To the best
of our knowledge, this is the first reported case of large aorto-pulmonary
collateral closed successfully with an Amplatzer Ductal Occluder II device.
PMID- 26432737
TI - Postoperative diffuse coronary spasm after two valve surgery - a rare phenomenon.
AB - Postoperative coronary artery spasm is one of the grave complications of cardiac
surgery and is usually seen in patients undergoing coronary artery bypass
surgery. We describe the case of a 63 year old male patient developing
postoperative spasm of the entire coronary tree after aortic & mitral valve
replacement, manifesting as significant electrocardiographic changes. Urgent
coronary angiography was performed which revealed diffuse spasm of the entire
coronary tree. It resolved completely with intracoronary injection of
Nitroglycerine. The present case highlights the likelihood of postoperative
coronary spasm even after valve replacement surgery, and not just coronary bypass
surgery. It also illustrated the usefulness of coronary angiography for both
diagnosis and treatment of this entity.
PMID- 26432738
TI - Wong's anomaly - a rare variant of cor triatriatum.
AB - Cor triatriatum sinistrum is an extremely rare congenital heart disease. It is
even more uncommon in adults, and clinically significant mitral valve lesion
complicating cor triatriatum is distinctly rare. Wong et al reported for the
first time the rare combination of cor triatriatum sinister associated with
severe mitral regurgitation and abnormal tensor apparatus of the mitral valve. We
report a similar case and used the term Wong's anomaly for the syndrome, having
membranous type of cor triatriatum sinistrum, severe mitral regurgitation and
hypoplasia of the papillary muscles and short chordae. Color Doppler
Echocardiography showed peculiar 'helmet sign' of mitral regurgitation, wherein
the mitral regurgitation color jet fills the distal atrial chamber and abruptly
ends in a horizontal plane as it is halted by the intra-atrial membrane.
PMID- 26432739
TI - 'Action potential-like' ST elevation following pseudo-Wellens' electrocardiogram.
AB - Coronary artery vasospasm is an important cause of chest pain syndromes that can
lead to myocardial infarction, ventricular arrhythmias, and sudden death. In
1959, Prinzmetal et al described a syndrome of nonexertional chest pain with ST
segment elevation on electrocardiography. Persistent angina is challenging, and
repeated coronary angioplasty may be required in this syndrome. Calcium
antagonists are extremely effective in treating and preventing coronary spasm,
and may provide long-lasting relief for the patient. Whereas the Wellens'
syndrome is characterized by symmetrically inverted T-waves with preserved R
waves in the precordial leads suggestive of impending myocardial infarction due
to a critical proximal left anterior descending stenosis, the pseudo-Wellens'
syndrome caused by coronary artery spasm has also rarely been reported in
literature. We present a pseudo-Wellens syndrome as a cause of vasospastic
angina, and a diffuse ST segment elavation on electrocardiogram resembling the
Greek letter lambda, called also 'action potential-like' ECG in a patient with
vasospastic-type Printzmetal angina.
PMID- 26432740
TI - Challenges in coronary CTO intervention after TAVR: a case report and discussion.
AB - Progression of coronary arteries after transcatheter aortic valve replacement is
an important issue. Coronary revascularization in these patients can be
challenging because of potential hindrance posed by the artificial valve
structure in getting access to the coronary ostium. This gets even more difficult
in chronic total occlusions (CTOs) that represent the most complex subset of
coronary lesions. We report the first case of coronary CTO revascularization in a
patient who underwent TAVR a few months prior and discuss the complexities
involved in intervening such lesions.
PMID- 26432741
TI - Apparently intact mitral valve repair complicated with hemolytic anemia.
PMID- 26432742
TI - Systolic murmur in a young man who had previous ventricular septal defect repair:
the double-chambered right ventricle.
PMID- 26432743
TI - The evanescent right atrial mass.
AB - An unusual cause of pulmonary emboli from an evanescent right atrial mass is
described in this case report. The systematic approach from initial presentation
to a definite diagnosis of a rare condition is described.
PMID- 26432744
TI - Double chamber right ventricle and left ventricle: a rare association.
PMID- 26432745
TI - Missing diagnosis: gingival hypertrophy due to amlodipine.
AB - Gingival hypertrophy (GH) is a well-known physical manifestation due to
inflammatory conditions, pregnancy, vitamin C deficiency, systemic diseases like
leukemia, Wegners granulomatosis, and various drugs like anticonvulsants,
immunosuppresant, and calcium channel blockers (CCBs).We present here a case of a
45-year-old woman, who has been taking Amlodipine 10mg once a day together with
Atenelol 50mg per day for one and half years, and has subsequently developed gum
hypertrophy. This manifestation was reversed after stopping of Amlodipine. Though
this case presentation is described in literature, we hereby present it in a
pictorial form, to sensitize the treating physician toward it.
PMID- 26432746
TI - Successful coil embolization of a bleeding internal thoracic artery that caused
severe hypotension immediately after permanent pacemaker placement.
PMID- 26432747
TI - Dabigatran for left ventricular thrombus.
AB - Male patient in dilated phase of hypertrophic cardiomyopathy had multiple
hospitalizations during the past 2 years either due to congestive heart failure,
stroke, scar epilepsy, or atrial fibrillation and ventricular tachycardia.
Medication included evidence based therapy for heart failure, cordarone and
warfarin. Anticoagulation had to be discontinued due to marked fluctuations in
INR. Transthoracic Echocardiography (TTE) revealed a mobile mass in the left
ventricle. He was treated with Dabigatran 110mg twice a day for 4 months without
any bleeding or embolic episode and complete resolution of thrombus. Dabigatran
is a reversible direct thrombin inhibitor and currently approved for the
prevention of thromboembolic episodes in non-valvar atrial fibrillation. This
case demonstrates possible thrombolytic properties of dabigatran in resolution of
left ventricular thrombus.
PMID- 26432749
TI - Calcific aortic valve disease: is it another face of atherosclerosis?
AB - Calcific aortic valve disease (CAVD) is the most common valvular heart disease in
the elderly. As life expectancy increases, prevalence of CAVD is expected to
rise. CAVD is characterized by progressive dystrophic calcification of aortic
cusps. In the initial stages, the pathogenesis is similar to atherosclerosis,
characterized by basement membrane disruption, inflammation, cell infiltration,
lipid deposition, and calcification. Presence of osteopontin in calcified aortic
valves suggests pathological calcification and bone formation in these calcified
valves. Historical, experimental, genetic, and clinical evidences suggest that
CAVD and atherosclerosis share the same pathological sequences with common risk
factors. Understanding the two faces of atherosclerosis, the vascular and
valvular, will help us to prevent progression of aortic sclerosis to aortic
stenosis, by controlling modifiable risk factors and by initiating statin therapy
in them. However, the knowledge about these preventive measures and drugs is
scanty. In this review article, an attempt is made to unfurl the relation between
atherosclerosis and CAVD.
PMID- 26432748
TI - Framework for a National STEMI Program: consensus document developed by STEMI
INDIA, Cardiological Society of India and Association Physicians of India.
AB - The health care burden of ST elevation myocardial infarction (STEMI) in India is
enormous. Yet, many patients with STEMI can seldom avail timely and evidence
based reperfusion treatments. This gap in care is a result of financial barriers,
limited healthcare infrastructure, poor knowledge and accessibility of acute
medical services for a majority of the population. Addressing some of these
issues, STEMI India, a not-for-profit organization, Cardiological Society of
India (CSI) and Association Physicians of India (API) have developed a protocol
of "systems of care" for efficient management of STEMI, with integrated networks
of facilities. Leveraging newly-developed ambulance and emergency medical
services, incorporating recent state insurance schemes for vulnerable populations
to broaden access, and combining innovative, "state-of-the-art" information
technology platforms with existing hospital infrastructure, are the crucial
aspects of this system. A pilot program was successfully employed in the state of
Tamilnadu. The purpose of this article is to describe the framework and methods
associated with this programme with an aim to improve delivery of reperfusion
therapy for STEMI in India. This programme can serve as model STEMI systems of
care for other low-and-middle income countries.
PMID- 26432750
TI - Transradial approach for coronary angiogram: something not to be neglected.
PMID- 26432752
TI - Atrazine triggers developmental abnormality of ovary and oviduct in quails
(Coturnix Coturnix coturnix) via disruption of hypothalamo-pituitary-ovarian
axis.
AB - There has been a gradual increase in production and consumption of atrazine (ATR)
in agriculture to meet the population rising demands. Female reproduction is
necessary for growth and maintenance of population. However, ATR impact on
females and particularly ovarian developmental toxicity is less clear. The aim of
this study was to define the pathways by which ATR exerted toxic effects on
ovarian development of ovary and hypothalamo-pituitary-ovarian (HPO) axis. Female
quails were dosed by oral gavage from sexual immaturity to maturity with 0, 50,
250 and 500 mg ATR/kg/d for 45 days. ATR had no effect on mortality but depressed
feed intake and growth and influenced the biochemical parameters. Notably, the
arrested development of ovaries and oviducts were observed in ATR-exposed quails.
The circulating concentrations of E2, P, LH and PRL were unregulated and FSH and
T was downregulated in ATR-treated quails. The mRNA expression of GnRH in
hypothalamo and LH in pituitary and FSH in ovary was downregulated significantly
by ATR exposure and FSH and PRL in pituitary were upregulated. ATR exposure
upregulated the level of P450scc, P450arom, 3beta-HSD and 17beta-HSD in ovary and
downregulated ERbeta expression in female quails. However, ATR did not change
ERalpha expression in ovary. This study provides new insights regarding female
productive toxicology of ATR exposure. Ovary and oviduct in sexually maturing
females were target organs of ATR-induced developmental toxicity. We propose that
ATR-induced developmental abnormality of ovary and oviduct is associated with
disruption of gonadal hormone balance and HPO axis in female quails.
PMID- 26432754
TI - What went wrong at Addenbrooke's?
PMID- 26432753
TI - Molecular imaging of aurora kinase A (AURKA) expression: Synthesis and
preclinical evaluation of radiolabeled alisertib (MLN8237).
AB - INTRODUCTION: Survival of patients after resection of colorectal cancer liver
metastasis (CRCLM) is 36%-58%. Positron emission tomography (PET) tracers,
imaging the expression of prognostic biomarkers, may contribute to assign
appropriate management to individual patients. Aurora kinase A (AURKA) expression
is associated with survival of patients after CRCLM resection. METHODS: We
synthesized [(3)H]alisertib and [(11)C]alisertib, starting from [(3)H]methyl
nosylate and [(11)C]methyl iodide, respectively. We measured in vitro uptake of
[(3)H]alisertib in cancer cells with high (Caco2), moderate (A431, HCT116, SW480)
and low (MKN45) AURKA expression, before and after siRNA-mediated AURKA
downmodulation, as well as after inhibition of P-glycoprotein (P-gp) activity. We
measured in vivo uptake and biodistribution of [(11)C]alisertib in nude mice,
xenografted with A431, HCT116 or MKN45 cells, or P-gp knockout mice. RESULTS:
[(3)H]Alisertib was synthesized with an overall yield of 42% and [(11)C]alisertib
with an overall yield of 23%+/-9% (radiochemical purity >=99%). Uptake of
[(3)H]alisertib in Caco2 cells was higher than in A431 cells (P=.02) and higher
than in SW480, HCT116 and MKN45 cells (P<.01). Uptake in A431 cells was higher
than in SW480, HCT116 and MKN45 cells (P<.01). Downmodulation of AURKA expression
reduced [(3)H]alisertib uptake in Caco2 cells (P<.01). P-gp inhibition increased
[(3)H]alisertib uptake in Caco2 (P<.01) and MKN45 (P<.01) cells. In vivo
stability of [(11)C]alisertib 90min post-injection was 94.7%+/-1.3% and tumor-to
background ratios were 2.3+/-0.8 (A431), 1.6+/-0.5 (HCT116) and 1.9+/-0.5
(MKN45). In brains of P-gp knockout mice [(11)C]alisertib uptake was increased
compared to uptake in wild-type mice (P<.01) CONCLUSIONS: Radiolabeled alisertib
can be synthesized and may have potential for the imaging of AURKA, particularly
when AURKA expression is high. However, the exact mechanisms underlying alisertib
accumulation need further investigation. ADVANCES IN KNOWLEDGE AND IMPLICATIONS
FOR PATIENT CARE: Radiolabeled alisertib may be used for non-invasively measuring
AURKA protein expression and to stratify patients for treatment accordingly.
PMID- 26432755
TI - Hemisynthesis, Antitumoral Effect, and Molecular Docking Studies of Ferutinin and
Its Analogues.
AB - The natural product ferutinin was shown to act as an agonist to estrogen receptor
ERalpha and agonist/antagonist to ERbeta featuring a weak antiproliferative
activity toward breast cancer cells. To enhance this activity, ferutinin
analogues were synthesized by esterification of jaeschkenadiol with different
acids. These compounds were assayed for their in vitro antiproliferative activity
against estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) breast
cancer cell lines. Among the compounds, 3c' exhibited a potent inhibitory
selective activity against MCF-7 with IC50 value of 1 MUM. Docking simulation of
3c' in the ligand binding domain of the ERs indicated a potential antagonism
interaction with both ER subtypes. Functional assay showed that 3c' binds as an
antagonist to ERalpha protein while ferutinin acts as an agonist.
PMID- 26432758
TI - Protein-caloric dietary restriction inhibits mossy fiber sprouting in the
pilocarpine model of TLE without significantly altering seizure phenotype.
AB - Given the known effects of undernutrition over protein synthesis, we promoted
neonatal undernutrition to evaluate its effect over the neuroplasticity induced
by the pilocarpine model of epilepsy and also over spontaneous seizure
expression. A well-nourished group (WN), fed ad libitum rat chow diet, and an
undernourished group (UN), fed 60% of the amount of diet consumed by a WN group,
were submitted to status epilepticus (SE) through pilocarpine injection at 45
days of age. Thereafter, animals were behaviorally monitored for 6h daily to
quantify seizures. On the 120th day, electroencephalography (EEG) was recorded
and rats were sacrificed to measure proteins and glutamate release from
hippocampus. Neo-Timm staining was used to detect mossy fiber sprouting. The
results indicate no statistical difference in the latency for the first
spontaneous recurrent seizure (SRS), in the number of daily SRS, or in EEG
epileptiform activity duration between groups. However, PILO promoted more K(+)
stimulated glutamate release in the hippocampus slices from WN animals when
compared to the UN group. It was also found a lower degree of mossy fibers
sprouting in UN group. Data from this work, thus, indicate that the decreased
neuroplasticity as currently measured does not directly impact on the
manifestation of spontaneous seizures.
PMID- 26432751
TI - Deregulation of F-box proteins and its consequence on cancer development,
progression and metastasis.
AB - F-box proteins are substrate receptors of the SCF (SKP1-Cullin 1-F-box protein)
E3 ubiquitin ligase that play important roles in a number of physiological
processes and activities. Through their ability to assemble distinct E3 ubiquitin
ligases and target key regulators of cellular activities for ubiquitylation and
degradation, this versatile group of proteins is able to regulate the abundance
of cellular proteins whose deregulated expression or activity contributes to
disease. In this review, we describe the important roles of select F-box proteins
in regulating cellular activities, the perturbation of which contributes to the
initiation and progression of a number of human malignancies.
PMID- 26432760
TI - Posttraumatic seizures and epilepsy in adult rats after controlled cortical
impact.
AB - Posttraumatic epilepsy (PTE) has been modeled with different techniques of
experimental traumatic brain injury (TBI) using mice and rats at various ages. We
hypothesized that the technique of controlled cortical impact (CCI) could be used
to establish a model of PTE in young adult rats. A total of 156 male Sprague
Dawley rats of 2-3 months of age (128 CCI-injured and 28 controls) was used for
monitoring and/or anatomical studies. Provoked class 3-5 seizures were recorded
by video monitoring in 7/57 (12.3%) animals in the week immediately following CCI
of the right parietal cortex; none of the 7 animals demonstrated subsequent
spontaneous convulsive seizures. Monitoring with video and/or video-EEG was
performed on 128 animals at various time points 8-619 days beyond one week
following CCI during which 26 (20.3%) demonstrated nonconvulsive or convulsive
epileptic seizures. Nonconvulsive epileptic seizures of >10s were demonstrated in
7/40 (17.5%) animals implanted with 2 or 3 depth electrodes and usually
characterized by an initial change in behavior (head raising or animal alerting)
followed by motor arrest during an ictal discharge that consisted of high
amplitude spikes or spike-waves with frequencies ranging between 1 and 2Hz class
3-5 epileptic seizures were recorded by video monitoring in 17/88 (19%) and by
video-EEG in 2/40 (5%) CCI-injured animals. Ninety of 156 (58%) animals (79 CCI
injured, 13 controls) underwent transcardial perfusion for gross and microscopic
studies. CCI caused severe brain tissue loss and cavitation of the ipsilateral
cerebral hemisphere associated with cell loss in the hippocampal CA1 and CA3
regions, hilus, and dentate granule cells, and thalamus. All Timm-stained CCI
injured brains demonstrated ipsilateral hippocampal mossy fiber sprouting in the
inner molecular layer. These results indicate that the CCI model of TBI in adult
rats can be used to study the structure-function relationships that underlie
epileptogenesis and PTE.
PMID- 26432761
TI - [Influenza vaccination in risk groups. 2013-2014 season in the Community of
Valencia].
PMID- 26432759
TI - Pilocarpine-induced status epilepticus in mice: A comparison of spectral analysis
of electroencephalogram and behavioral grading using the Racine scale.
AB - Pilocarpine-induced status epilepticus (SE) is a widely used seizure model in
mice, and the Racine scale has been used to index seizure intensity. The goal of
this study was to analyze electroencephalogram (EEG) quantitatively using fast
Fourier transformation (FFT) and statistically evaluate the correlation of
electrographic seizures with convulsive behaviors. Simultaneous EEG and video
recordings in male mice in a mixed genetic background were conducted and
pilocarpine was administered intraperitoneally to induce seizures. The videos
were graded using the Racine scale and the root-mean-square (RMS) power analysis
of EEG was performed with Sirenia Seizure Pro software. We found that the RMS
power was very weakly correlated with convulsive behavior induced by pilocarpine.
Convulsive behaviors appeared long before electrographic seizures and showed a
strong negative correlation with theta frequency activity and a moderate positive
correlation with gamma frequency activity. Racine scores showed moderate
correlations with RMS power across multiple frequency bands during the transition
from first electrographic seizure to SE. However, there was no correlation
between Racine scores and RMS power during the SE phase except a weak correlation
with RMS power in the theta frequency. Our analysis reveals limitations of the
Racine scale as a primary index of seizure intensity in status epilepticus, and
demonstrates a need for quantitative analysis of EEG for an accurate assessment
of seizure onset and severity.
PMID- 26432762
TI - [Co-existence of Crohn's disease and primary immune thrombocytopenia and its
implications in treatment].
PMID- 26432763
TI - Targeting Treg signaling for the treatment of autoimmune diseases.
AB - Regulatory T (Treg) cells are crucial players in the prevention of autoimmunity.
Treg lineage commitment and functional stability are influenced by selected
extracellular signals from the local environment, shaped by distinctive
intracellular signaling network, and secured by their unique epigenetic profile.
Recent advances in our understanding of the complex processes of Treg lineage
differentiation, maintenance, and function has paved the way for developing
strategies to manipulate these important cells for therapeutic benefit in many
diseases. In this review, we will summarize recent advances in our understanding
of Treg biology as well as Treg-targeted therapies in the context of autoimmune
disease.
PMID- 26432764
TI - Posttranscriptional T cell gene regulation to limit Tfh cells and autoimmunity.
AB - T follicular helper (Tfh) cells are crucial to induce protective extrafollicular
and germinal center antibody responses against protein antigens. Over the last
decade, control of Tfh cell numbers has emerged as an important regulatory
checkpoint which, when perturbed, may lead to production of autoantibodies.
Recent progress in understanding how Tfh cells are kept limiting has revealed an
important role for posttranscriptional control of gene expression mediated by
microRNAs such as miR-17 ~ 92, miR-155 and miR-146a, and the RNA-binding proteins
Roquin and Regnase. Additionally, T cell microRNAs dysregulated in patients with
systemic lupus erythematosus have been shown to influence processes such as DNA
hypomethylation, IL-2 and CCL5 secretion, and Treg function, which contribute to
autoantibody formation and tissue damage.
PMID- 26432766
TI - [Haematological toxicity during treatment with albendazole].
PMID- 26432767
TI - The Impact of Uninterrupted Warfarin on Hand and Wrist Surgery.
AB - PURPOSE: To determine the impact of uninterrupted use of warfarin on hand and
wrist surgery. METHODS: This single-center, prospective cohort trial enrolled
adult patients undergoing hand and wrist surgery. Between May 2009 and August
2014, 47 surgical patients receiving uninterrupted warfarin (50 procedures) were
enrolled and matched as a group by age and procedure type to 48 surgical patients
(50 procedures) who were not prescribed warfarin. Complications, defined as
bleeding, infection, or wound dehiscence requiring reoperation, were recorded for
each group. Surgical outcome measures were composed of objective findings
affected by surgical site bleeding (ie, ecchymosis extent, hematoma presence, 2
point discrimination) and standardized patient-rated assessments (Quick
Disabilities of the Arm, Shoulder, and Hand, and visual analog scales: pain and
swelling). We collected data preoperatively and at 2 and 4 weeks postoperatively.
Statistical analyses contrasted complications and outcomes data between patient
groups. RESULTS: One procedure (2%; 95% confidence interval, 0% to 11%) in a
patient taking warfarin was complicated by hematoma requiring reoperation
resulting from an elevated postoperative international normalized ratio of 5.4.
There were no complications among controls (0%; 95% confidence interval, 0% to
7%). At 2 weeks postoperatively, patients receiving warfarin more frequently had
hematomas (28% vs 10%) and demonstrated a greater extent of ecchymosis from the
surgical incision (50 vs 19 mm). At 4 weeks, no differences existed in hematoma
presence or extent of ecchymosis between groups. The incidence of transiently
elevated 2-point discrimination was not different between groups (10% warfarin;
6% controls). Visual analog scores for pain and swelling were not significantly
different between groups at any time. Differences in Quick-Disabilities of the
Arm, Shoulder, and Hand scores between groups did not exceed a minimal clinically
important difference. CONCLUSIONS: Uninterrupted use of warfarin in patients
undergoing surgery of the hand and wrist was associated with an infrequent risk
of bleeding complication requiring reoperation. Increased rates of hematoma and
ecchymosis in patients taking warfarin normalized by 4 weeks postoperatively.
TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.
PMID- 26432768
TI - The Effect of Progressive Extensor Retinaculum Excision on Wrist Biomechanics and
Bowstringing.
AB - PURPOSE: To quantify the effect of the extensor retinaculum in preventing
bowstringing and extensor lag. METHODS: The extensor carpi radialis brevis (ECRB)
and extensor digitorum communis (EDC) tendons to the middle finger were isolated
in 6 human cadaveric specimens. Extensor tendon excursion and bowstringing were
measured as the extensor retinaculum was serially excised. RESULTS: For the
second dorsal compartment, extensor lag averaged 7 degrees when the entire
retinaculum over the ECRB was excised. Bowstringing did increase with sequential
resections and was greater for distal resections than for proximal resections.
When the entire retinaculum over the ECRB was removed, bowstringing averaged 12
mm. For the fourth dorsal compartment, excision of the distal retinaculum
resulted in more bowstringing and extensor lag than excision of the proximal
retinaculum. When the proximal two-thirds was excised, EDC extensor lag averaged
12 degrees and bowstringing averaged 9 mm; with the distal two-thirds excised,
extensor lag averaged 18 degrees and bowstringing averaged 14 mm. Complete
retinaculum excision resulted in EDC bowstringing of about 61 mm and extensor lag
of 80 degrees . CONCLUSIONS: Resection of the entire extensor retinaculum over
the second dorsal compartment results in minimal extensor lag and minimal
bowstringing. Resection of the entire retinaculum over the fourth dorsal
compartment results in massive extensor lag and bowstringing and should be
avoided. The distal portion of the retinaculum is most important in preventing
extensor lag and bowstringing for the fourth compartment. CLINICAL RELEVANCE: The
findings inform the surgeon's handling of the extensor retinaculum during
procedures on the dorsum of the wrist, especially when portions are to be
excised, transposed, or repaired.
PMID- 26432769
TI - Thyroid disrupting effects of polychlorinated biphenyls in ovariectomized rats: A
benchmark dose analysis.
AB - Polychlorinated biphenyls (PCBs) are proved endocrine disrupting potentials.
Reference points (RP) for PCBs are derived from dose-response relationship
analysis by using the traditional no observed adverse effect or lowest observed
adverse effect level (NOAEL/LOAEL) methods, or a more advanced benchmark dose
(BMD) method. In present study, toxicological RP for PCBs' thyroid disruption was
established and compared between NOAEL/LOAEL and BMD method in an ovariectomized
(OVX) rat model. Sham and OVX controls were given corn oil while other OVX groups
were administered with 0.1, 1.0, 5.0, and 10.0mg/kg bw of PCBs (aroclor 1254)
respectively by gavage. Body weight change, liver type I 5'-deiodinase (5'-DI)
activity, serum total thyroxine (tT4), triiodothyroxine (tT3), thyroid
stimulating hormones (TSH), and thyroid histopathological changes were measured
and analyzed. In PCBs-treated groups, serum tT4, tT3, TSH, and histopathological
examinations showed significant changes with a dose-dependent manner compared
with those in OVX control (P<0.05). The toxicological RP for PCBs affecting
thyroid function of OVX rats was 0.02 mg/kg'bw based on BMD analysis.
PMID- 26432770
TI - In utero exposure of neonatal buffalo calves to pesticide residues and the
alterations within their reproductive tract.
AB - In utero exposure of neonates to pesticide residues could be damaging to the
reproductive tract. Hence, the present study assessed the circulating
concentrations of pesticide residues in buffalo and their neonatal calves as well
as in the reproductive tract tissue samples of same calves. Also,
histopathological alterations were revealed in the reproductive tract of calves.
Pesticide residues were high (P<0.05) in the reproductive tract of calves (119.5
+/- 20.2 ng/g, 35% positive) in comparison to their blood (32.1 +/- 8.4 ng/ml,
15% positive) or blood of their dams (41.5 +/- 8.3 ng/ml, 25% positive). The
number of histopathological alterations were high (P<0.05) in the reproductive
tract of a calf contaminated with high concentrations of pesticide residues (3.43
+/- 1.29) in comparison to a tract positive for low residue concentrations (1.57
+/- 0.60) or pesticide negative tract (0.28 +/- 0.10). In conclusion, in utero
exposure of neonatal buffalo calves to pesticide residues may be associated with
damaging alterations in their reproductive tract.
PMID- 26432771
TI - Prevention of cyclophosphamide-induced hepatotoxicity and genotoxicity: Effect of
an L-cysteine based oxovanadium(IV) complex on oxidative stress and DNA damage.
AB - Vanadium has been emerged as a promising agent owing to its ability to prevent
several types of cancer. This study was aimed to investigate the protective role
of an organovanadium complex, viz., oxovanadium(IV)-L-cysteine methyl ester (VC
IV) against cyclophosphamide (CP)-induced hepatotoxicity and genotoxicity in
mice. Oral administration of VC-IV quite effectively ameliorated CP-induced
histopathological lesions and reduced levels of alanine transaminase, aspartate
transaminase and alkaline phosphatase. In addition, VC-IV significantly
attenuated CP-induced oxidative stress in the liver as evident from levels of
reactive oxygen species, nitric oxide and lipid peroxidation. Restoration of
glutathione level and activities of antioxidant enzymes (superoxide dismutase,
catalase, glutathione peroxidase and glutathione-S-transferase) were also
observed upon VC-IV administration. Moreover, VC-IV significantly mitigated CP
induced chromosomal aberrations, micronuclei formation, DNA fragmentation and
apoptosis in bone marrow cells and DNA damage in lymphocytes. The present study
showed that VC-IV could provide adequate protection against CP-induced
hepatotoxicity and genotoxicity in vivo.
PMID- 26432772
TI - Epigenetic modulation of Chlorella (Chlorella vulgaris) on exposure to polycyclic
aromatic hydrocarbons.
AB - DNA methylation in promoter region can be a new chemopreventive marker against
polycyclic aromatic hydrocarbons (PAHs). We performed a randomized, double blind
and cross-over trial (N=12 healthy females) to evaluate chlorella (Chlorella
vulgaris)-induced epigenetic modulation on exposure to PAHs. The subjects
consumed 4 tablets of placebo or chlorella supplement (total chlorophyll ~
8.3mg/tablet) three times a day before meals for 2 weeks. When the subjects
consumed chlorella, status of global hypermethylation (5-methylcytosine) was
reduced, compared to placebo (p=0.04). However, DNA methylation at the DNMT1 or
NQO1 was not modified by chlorella. We observed the reduced levels of urinary 1
hydroxypyrene (1-OHP), a typical metabolite of PAHs, by chlorella intake (p<0.1)
and a positive association between chlorella-induced changes in global
hypermethylation and urinary 1-OHP (p<0.01). Therefore, our study suggests
chlorella works for PAH-detoxification through the epigenetic modulation, the
interference of ADME of PAHs and the interaction of mechanisms.
PMID- 26432773
TI - Quercetin induces hepatic gamma-glutamyl hydrolase expression in rats by
suppressing hepatic microRNA rno-miR-125b-3p.
AB - Exogenous factors such as food components including the flavonoid quercetin are
suspected to influence micro RNA (miRNA) concentrations and thus possibly target
enzymes involved in xenobiotic metabolism. This study therefore investigates the
influence of orally administered quercetin on hepatic miRNA and the
identification of enzyme target mRNAs relevant in drug metabolism. Male Wistar
rats (n=16) were fed either a diet without (C) or with (Q) the addition of 100
ppm quercetin for 7 weeks and subsequently euthanized at the end of the dark
phase. To avoid strong effects of food deprivation on hepatic metabolism, food
was not removed until 5 h prior to the procedure. Liver was immediately dissected
and snap-frozen in liquid nitrogen. Concentrations of 352 hepatic miRNA were
measured in pool samples of each dietary group (n=8) using the RT(2) miRNA PCR
Array System. Differential expression of miRNAs was assumed with fold changes
>=3. Target genes of differentially expressed miRNAs were identified using the
database TargetScan. Because rno-miR-125b-3p showed the most prominent fold
change (-9) we further analyzed the expression of its top predicted target gene
gamma-glutamyl hydrolase (GGH) by quantitative real-time PCR using hypoxanthine
phosphoribosyltransferase 1 (hprt1) as endogenous control. Compared to controls,
23 miRNAs were differentially expressed in rats fed quercetin. A ninefold
reduction in hepatic miRNA rno-miR-125b-3p was paralleled by significant
induction of GGH mRNA in liver of quercetin fed rats. Because increased GGH
expressions were repeatedly associated with resistance to methotrexate,
concomitant intake with quercetin should be monitored carefully.
PMID- 26432774
TI - Is the artificial pancreas coming to a home near you?
PMID- 26432775
TI - 2 month evening and night closed-loop glucose control in patients with type 1
diabetes under free-living conditions: a randomised crossover trial.
AB - BACKGROUND: An artificial pancreas (AP) that can be worn at home from dinner to
waking up in the morning might be safe and efficient for first routine use in
patients with type 1 diabetes. We assessed the effect on glucose control with use
of an AP during the evening and night plus patient-managed sensor-augmented pump
therapy (SAP) during the day, versus 24 h use of patient-managed SAP only, in
free-living conditions. METHODS: In a crossover study done in medical centres in
France, Italy, and the Netherlands, patients aged 18-69 years with type 1
diabetes who used insulin pumps for continuous subcutaneous insulin infusion were
randomly assigned to 2 months of AP use from dinner to waking up plus SAP use
during the day versus 2 months of SAP use only under free-living conditions.
Randomisation was achieved with a computer-generated allocation sequence with
random block sizes of two, four, or six, masked to the investigator. Patients and
investigators were not masked to the type of intervention. The AP consisted of a
continuous glucose monitor (CGM) and insulin pump connected to a modified
smartphone with a model predictive control algorithm. The primary endpoint was
the percentage of time spent in the target glucose concentration range (3.9-10.0
mmol/L) from 2000 to 0800 h. CGM data for weeks 3-8 of the interventions were
analysed on a modified intention-to-treat basis including patients who completed
at least 6 weeks of each intervention period. The 2 month study period also
allowed us to asses HbA1c as one of the secondary outcomes. This trial is
registered with ClinicalTrials.gov, number NCT02153190. FINDINGS: During 2000
0800 h, the mean time spent in the target range was higher with AP than with SAP
use: 66.7% versus 58.1% (paired difference 8.6% [95% CI 5.8 to 11.4], p<0.0001),
through a reduction in both mean time spent in hyperglycaemia (glucose
concentration >10.0 mmol/L; 31.6% vs 38.5%; -6.9% [-9.8% to -3.9], p<0.0001) and
in hypoglycaemia (glucose concentration <3.9 mmol/L; 1.7% vs 3.0%; -1.6% [-2.3 to
-1.0], p<0.0001). Decrease in mean HbA1c during the AP period was significantly
greater than during the control period (-0.3% vs -0.2%; paired difference -0.2
[95% CI -0.4 to -0.0], p=0.047), taking a period effect into account (p=0.0034).
No serious adverse events occurred during this study, and none of the mild-to
moderate adverse events was related to the study intervention. INTERPRETATION:
Our results support the use of AP at home as a safe and beneficial option for
patients with type 1 diabetes. The HbA1c results are encouraging but preliminary.
FUNDING: European Commission.
PMID- 26432776
TI - Evidence for a natural humoral response in dairy cattle affected by persistent
botulism sustained by non-chimeric type C strains.
AB - Bovine botulism is a sporadic acute disease that usually causes catastrophic
losses in the herds. The unusual clinical evolution of a persistent mild outbreak
in a dairy herd, prompted us to characterize the neurotoxin gene profile of the
strain involved and to evaluate whether seroconversion had occurred. Diagnosis
was based on mild classical symptoms and was supported by PCR and bacteriological
findings, which revealed the involvement of a non-mosaic type C strain. An in
house ELISA was developed to detect antibodies to botulinum neurotoxin type C and
its performance was evaluated in a vaccination study. Fifty days after the index
case, fecal and serum samples were collected from the 14 animals of the herd and
screened for Clostridium botulinum and anti-botulinum neurotoxin antibodies type
C, respectively. The in-house developed ELISA was also used to test 100 sera
samples randomly collected from 20 herds. Strong ELISA reactions were observed in
3 convalescent and 5 asymptomatic animals involved in the studied outbreak. The
ELISA-positive cows all tested positive for non-mosaic C. botulinum type C in the
feces and the same strain was also detected in the alfalfa hay, suspected to be
the carrier source. Ten out of the 100 randomly collected sera tested positive
for anti-botulinum neurotoxin type C antibodies: 7 had borderline values and 3
from the same herd showed titers three times higher than the cut-off. We
concluded that type C botulism in cattle may occur with variable severity and
that prolonged exposure to sublethal doses of botulinum neurotoxin C may occur,
resulting in detectable antibodies.
PMID- 26432777
TI - Heterogeneous infectiousness in guinea pigs experimentally infected with
Trypanosoma cruzi.
AB - Guinea pigs are important reservoirs of Trypanosoma cruzi, the causative parasite
of Chagas disease, and in the Southern Cone of South America, transmission is
mediated mainly by the vector Triatoma infestans. Interestingly, colonies of
Triatoma infestans captured from guinea pig corrals sporadically have infection
prevalence rates above 80%. Such high values are not consistent with the
relatively short 7-8 week parasitemic period that has been reported for guinea
pigs in the literature. We experimentally measured the infectious periods of a
group of T. cruzi-infected guinea pigs by performing xenodiagnosis and direct
microscopy each week for one year. Another group of infected guinea pigs received
only direct microscopy to control for the effect that inoculation by triatomine
saliva may have on parasitemia in the host. We observed infectious periods longer
than those previously reported in a number of guinea pigs from both the
xenodiagnosis and control groups. While some guinea pigs were infectious for a
short time, other "super-shedders" were parasitemic up to 22 weeks after
infection, and/or positive by xenodiagnosis for a year after infection. This
heterogeneity in infectiousness has strong implications for T. cruzi transmission
dynamics and control, as super-shedder guinea pigs may play a disproportionate
role in pathogen spread.
PMID- 26432778
TI - Assessment of the calcification of the nuchal ligament and osteophytes of the
cervical spine in obstructive sleep apnoea subjects and snorers.
AB - The previous reports suggest that obstructive sleep apnoea (OSA) is related to
metabolic syndrome, mineral metabolism disorders and cardiovascular disease. In
addition, a possible relationship between obesity and the calcification of
ligaments has been implied. However, the potential link between OSA and the
calcification of ligaments has not been directly studied. In this present study,
to investigate the potential link between OSA and the calcification of ligaments,
we examined the prevalence of the calcification of ligaments in OSA patients and
the relationship between these findings and OSA severity. Eighty consecutive
patients (60 males, 20 females) diagnosed as OSA or a heavy snorer based on full
night polyso-mnography were retrospectively recruited from May 2006 to July 2008.
Each patient underwent cephalometric imaging examination before the arrangement
of an oral appliance. One calibrated observer (YS) reviewed the cephalometric
images for the presence of calcification of the nuchal ligament and osteophytes
of the cervical spine. The prevalence of calcification of the nuchal ligament in
OSA patients and snorers was 46.3% (males: 52%, females: 30%) There was a
significant positive correlation between the severity of OSA (AHI) and the
calcification of the nuchal ligament before and after adjusting for BMI. The
prevalence of the calcification of the nuchal ligament in OSA subjects and
snorers was higher than in previous studies with non-OSA subjects. In addition,
it is suggested that the severity of OSA correlates with the presence of
calcification of the nuchal ligament.
PMID- 26432779
TI - Combination treatment with excimer laser and narrowband UVB light in vitiligo
patients.
AB - BACKGROUND: For the treatment of vitiligo, narrowband UVB (NBUVB) light is
considered the most effective for nonsegmental vitiligo, while excimer laser
treatment is commonly used for localized vitiligo. However, treatment areas may
potentially be missed with excimer laser treatment. OBJECTIVE: We aimed to
evaluate the effect of combinational treatment with NBUVB light and excimer laser
on vitiligo. METHODS: All patients were first treated with NBUVB; excimer laser
was then applied in conjunction with NBUVB phototherapy due to a slow response or
no further improvement with continuous NBUVB treatment alone. To minimize adverse
effects, a fixed dose of NBUVB was administered, and the dose of excimer laser
was increased based on patient response. RESULTS: Among 80 patients, 54 patients
showed responses after combination with excimer laser; however, 26 patients
(32.5%) showed no remarkable change after combination therapy. Of the 26 patients
who showed no further response, 12 patients (46.1%) presented with vitiligo on
the acral areas, which are known to the least responsive sites. CONCLUSION: Our
study suggests that combined treatment of NBUVB and excimer laser in vitiligo may
enhance the treatment response without remarkable side effects, therefore might
also increase the compliance of the patients to the treatment.
PMID- 26432780
TI - Increased p53 protein expression as a potential predictor of early relapse after
hematopoietic stem cell transplantation in children with acute myelogenous
leukemia.
AB - Dysregulation of genes involved in the cell cycle such as TP53, P21, P16, and
PTEN plays a key role in oncogenesis. We have earlier reported increased
expression of the TP53 encoded protein p53, in bone marrow samples from pediatric
patients with more aggressive, rare chronic myeloid malignancies. The aim of this
study was to investigate protein expression of p53, p21, p16, and PTEN before and
after HSCT in pediatric patients with AML and evaluate whether any potential
alterations could predict relapse after HSCT. Paraffin-embedded bone marrow
samples from 34 pediatric patients with AML were collected retrospectively from
time of diagnosis as well as pre- and post-HSCT. IHC was performed on tissue
microarrays with antibodies against p53, p21, p16, and PTEN. Study material was
analyzed by independent t-tests and nonlinear regression. t-Tests showed a
statistical significant difference in p53 (p = 0.010) with overexpression in the
group of patients who relapsed compared to the relapse-free patients at >3-6
months post-HSCT. Analysis of p53 protein expression by IHC may be a potential
predictor for relapse after HSCT in children with AML.
PMID- 26432781
TI - NHERF1 regulates actin cytoskeleton organization through modulation of alpha
actinin-4 stability.
AB - The actin cytoskeleton is composed of a highly dynamic network of filamentous
proteins, yet the molecular mechanism that regulates its organization and
remodeling remains elusive. In this study, Na(+)/H(+) exchanger regulatory factor
(NHERF)-1 loss-of-function and gain-of-function experiments reveal that
polymerized actin cytoskeleton (F-actin) in HeLa cells is disorganized by NHERF1,
whereas actin protein expression levels exhibit no detectable change. To
elucidate the molecular mechanism underlying actin cytoskeleton disorganization
by NHERF1, a combined 2-dimensional electrophoresis-matrix-assisted laser
desorption/ionization-time of flight mass spectrometry approach was used to
screen for proteins regulated by NHERF1 in HeLa cells. alpha-Actinin-4, an actin
cross-linking protein, was identified. Glutathione S-transferase pull-down and
coimmunoprecipitation studies showed the alpha-actinin-4 carboxyl-terminal region
specifically interacted with the NHERF1 postsynaptic density 95/disc-large/zona
occludens-1 domain. The NHERF1/alpha-actinin-4 interaction increased alpha
actinin-4 ubiquitination and decreased its expression levels, resulting in actin
cytoskeleton disassembly. Our study identified alpha-actinin-4 as a novel NHERF1
interaction partner and provided new insights into the regulatory mechanism of
the actin cytoskeleton by NHERF1.
PMID- 26432782
TI - Drp1, Mff, Fis1, and MiD51 are coordinated to mediate mitochondrial fission
during UV irradiation-induced apoptosis.
AB - Mitochondrial fission and proteins vital to this process play essential roles in
apoptosis. Several mitochondrial outer membrane proteins, including mitochondrial
fission protein 1 (Fis1), mitochondrial fission factor (Mff) and mitochondrial
dynamics of 51 kDa protein (MiD51), also known as mitochondrial elongation factor
1 (MEIF1), have been reported to promote mitochondrial fission by recruiting the
GTPase dynamin-related protein 1 (Drp1). However, it remains unclear how these
fission factors coordinate to control apoptotic mitochondrial fission. Molecular
studies have suggested the existence of interaction between Mff and Drp1, but
fundamental questions remain concerning their function. In the present study, we
reported that the phosphorylation status of Drp1-Ser(637) was essential for its
interaction with Mff. UV stimulation induced a decrease in cytoplasmic and
mitochondrial Drp1 phosphorylation on Ser(637) and enhanced the interaction
between Drp1 and Mff, resulting in mitochondrial fragmentation. Simultaneously,
the interaction increased markedly between Fis1 and MiD51/MIEF1, whereas the
interaction between Drp1 and MiD51/MIEF1 decreased significantly after UV
irradiation, which suggests that Fis1 competitively binds to MiD51/MIEF1 to
activate Drp1 indirectly. Moreover, Mff-Drp1 binding and Mff-mediated recruitment
of Drp1 to mitochondria did not require Bax during UV stimulation. Our study
revealed a novel role of Mff in regulation of mitochondrial fission and showed
how the fission proteins are orchestrated to mediate the fission process during
apoptosis.
PMID- 26432783
TI - The origin and implementation of the Broadening Experiences in Scientific
Training programs: an NIH common fund initiative.
AB - Recent national reports and commentaries on the current status and needs of the
U.S. biomedical research workforce have highlighted the limited career
development opportunities for predoctoral and postdoctoral trainees in academia,
yet little attention is paid to preparation for career pathways outside of the
traditional faculty path. Recognizing this issue, in 2013, the U.S. National
Institutes of Health (NIH) Common Fund issued a request for application titled
"NIH Director's Biomedical Research Workforce Innovation Award: Broadening
Experiences in Scientific Training (BEST)." These 5-yr 1-time grants, awarded to
17 single or partnering institutions, were designed to develop sustainable
approaches to broaden graduate and postgraduate training, aimed at creating
training programs that reflect the range of career options that trainees may
ultimately pursue. These institutions have formed a consortium in order to work
together to develop, evaluate, share, and disseminate best practices and
challenges. This is a first report on the early experiences of the consortium and
the scope of participating BEST programs. In this report, we describe the state
of the U.S. biomedical workforce and development of the BEST award, variations of
programmatic approaches to assist with program design without BEST funding, and
novel approaches to engage faculty in career development programs. To test the
effectiveness of these BEST programs, external evaluators will assess their
outcomes not only over the 5 yr grant period but also for an additional 10 yr
beyond award completion.
PMID- 26432785
TI - Prevalence and social drivers of HIV among married and cohabitating heterosexual
adults in south-eastern Tanzania: analysis of adult health community cohort data.
AB - BACKGROUND: In sub-Saharan Africa, the prevalence of HIV among married and
cohabiting couples is substantial. Information about the underlying social
drivers of HIV transmission in couples is critical for the development of
structural approaches to HIV prevention, but not readily available. We explored
the association between social drivers, practices, and HIV status among stable
couples in Ifakara, Tanzania. DESIGN: Using a cross-sectional design, we analyzed
data from a sample of 3,988 married or cohabiting individuals, aged 15 years and
older from the MZIMA adult health community cohort study of 2013.
Sociodemographic factors (sex, income, age, and education), gender norms
(perceived acceptability for a wife to ask her partner to use a condom when she
knows he is HIV positive), marriage characteristics (being in a monogamous or a
polygamous marriage, being remarried), sexual behavior practices (lifetime number
of sexual partners and concurrent sexual partners), health system factors (ever
used voluntary HIV counseling and testing), and lifestyle patterns (alcohol use)
were used to explore the odds of being HIV positive, with 95% confidence
intervals. RESULTS: Prevalence of HIV/AIDS was 6.7% (5.9% males and 7.1%
females). Gender norms, that is, perception that a woman is not justified to ask
her husband to use a condom even when she knows he has a disease (adjusted odds
ratio AOR=1.51, 95% CI 1.06-2.17), marital characteristics, that is, being
remarried (AOR=1.49, 95% CI 1.08-2.04), and sexual behavior characteristics, that
is, lifetime number of sexual partners (2-4: AOR=1.47, 95% CI 1.02-2.11; 5+:
AOR=1.61, 95% CI 1.05-2.47) were the main independent predictors of HIV
prevalence. CONCLUSIONS: Among married or cohabiting individuals, the key social
drivers/practices that appeared to make people more vulnerable for HIV are gender
norms, marriage characteristics (being remarried), and sexual behavior practices
(lifetime number of sexual partners). Married and cohabiting couples are an
important target group for HIV prevention efforts in Tanzania. In addition to
individual interventions, structural interventions are needed to address the
gender norms, remarriage, and sexual practices that shape differential
vulnerability to HIV in stable couples.
PMID- 26432784
TI - Joint association of physical activity and overweight with subsequent
psychotropic medication: a register-linked follow-up study among employees.
AB - BACKGROUND: Physical activity level and overweight have shown associations with
mental health problems but it is not known whether the risk of mental health
problems due to overweight varies by physical activity. We examined joint
association of physical activity and overweight with subsequent psychotropic
medication among 40-60-year-old employees. METHODS: The questionnaire survey data
were derived from Helsinki Health Study baseline postal questionnaires in 2000-02
among employees of the City of Helsinki aged 40-60 years (n = 8960, response rate
67%). Baseline survey data were linked with prospective register data on
prescribed psychotropic medication (ATC-codes N05 and N06, except N06D) among
those with written consent (74%) for such linkage. The analyses included 6169
responders (78% women, corresponding to the target population). We divided
participants into six groups according to their baseline self-reported body mass
index and leisure-time physical activity using physically highly active normal
weight participants as a reference group. We used Cox regression analysis
adjusted for age, gender, psychotropic medication prior to baseline, and
socioeconomic position, marital status, working conditions, limiting long
standing illness, alcohol use, and smoking. RESULTS: At baseline, 49% were
overweight and 23% were physically inactive. After adjusting for age and gender,
inactive normal-weight (hazard ratio (HR) 1.3, 95% CI 1.1-1.5), moderately active
overweight (HR 1.3, 95% CI 1.1-1.5) and inactive overweight (HR 1.4, 95% CI 1.2
1.6) had higher risk for any psychotropic medication compared with group of
highly active normal-weight. After adjusting for prior medication, only the
inactive overweight group had higher risk (HR 1.4, 95% CI 1.2-1.6). Other
covariates made but a minor contribution to the examined associations. For
antidepressants the associations were somewhat stronger than for sedatives.
CONCLUSIONS: Both normal-weight and physical activity help prevent psychotropic
medication but physical activity dominates the association over normal-weight.
PMID- 26432786
TI - Cabozantinib (XL184) Inhibits Growth and Invasion of Preclinical TNBC Models.
AB - PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive breast cancer
subtype that is associated with poor clinical outcome. There is a vital need for
effective targeted therapeutics for TNBC patients, yet treatment strategies are
challenged by the significant intertumoral heterogeneity within the TNBC subtype
and its surrounding microenvironment. Receptor tyrosine kinases (RTK) are highly
expressed in several TNBC subtypes and are promising therapeutic targets. In this
study, we targeted the MET receptor, which is highly expressed across several
TNBC subtypes. EXPERIMENTAL DESIGN: Using the small-molecule inhibitor
cabozantinib (XL184), we examined the efficacy of MET inhibition in preclinical
models that recapitulate human TNBC and its microenvironment. To analyze the
dynamic interactions between TNBC cells and fibroblasts over time, we utilized a
3D model referred to as MAME (Mammary Architecture and Microenvironment
Engineering) with quantitative image analysis. To investigate cabozantinib
inhibition in vivo, we used a novel xenograft model that expresses human HGF and
supports paracrine MET signaling. RESULTS: XL184 treatment of MAME cultures of
MDA-MB-231 and HCC70 cells (+/- HGF-expressing fibroblasts) was cytotoxic and
significantly reduced multicellular invasive outgrowths, even in cultures with
HGF-expressing fibroblasts. Treatment with XL184 had no significant effects on
MET(neg) breast cancer cell growth. In vivo assays demonstrated that cabozantinib
treatment significantly inhibited TNBC growth and metastasis. CONCLUSIONS: Using
preclinical TNBC models that recapitulate the breast tumor microenvironment, we
demonstrate that cabozantinib inhibition is an effective therapeutic strategy in
several TNBC subtypes.
PMID- 26432787
TI - Antimicrobial activity of Alcaligenes sp. HPC 1271 against multidrug resistant
bacteria.
AB - Alcaligenes sp. HPC 1271 demonstrated antibacterial activity against multidrug
resistant bacteria, Enterobacter sp., resistant to sulfamethoxazole, ampicillin,
azithromycin, and tetracycline, as well as against Serratia sp. GMX1, resistant
to the same antibiotics with the addition of netilmicin. The cell-free culture
supernatant was analyzed for possible antibacterials by HPLC, and the active
fraction was further identified by LC-MS. Results suggest the production of
tunicamycin, a nucleoside antibiotic. The draft genome of this bacterial isolate
was analyzed, and the 4.2 Mb sequence data revealed six secondary metabolite
producing clusters, identified using antiSMASH platform as ectoine,
butyrolactone, phosphonate, terpene, polyketides, and nonribosomal peptide
synthase (NRPS). Additionally, the draft genome demonstrated homology to the
tunicamycin-producing gene cluster and also defined 30 ORFs linked to protein
secretion that could also play a role in the antibacterial activity observed.
Gene expression analysis demonstrated that both NRPS and dTDP-glucose 4,6
dehydratase gene clusters are functional and could be involved in antibacterial
biosynthesis.
PMID- 26432788
TI - Peri-articular lymphatic system and "Bi" theory of Chinese medicine in the
pathogenesis and treatment of arthritis.
AB - Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most common joint
diseases, and they have characterization of synovial inflammation and cartilage
destruction, associated with the accumulation of numerous catabolic mediators and
inflammatory cells in the synovial space and surrounding soft tissues. How these
factors are cleared and if the "clearance" process contributes to pathogenesis of
arthritis are not known. Recently, we found the existence of the peri-articular
lymphatic system in mouse joints. The blockade of lymphangiogenesis and lymphatic
draining function accelerates while stimulation of lymphatic function attenuates
the severity of joint tissue lesions in mouse models of RA and OA. More
importantly, we noticed the similarity between the dysfunction of lymphatic
drainage in arthritic joints and "Bi" theory of Chinese medicine (CM), and
demonstrated that several Bi disease-treated herbal drugs directly affect the
function of lymphatic endothelial cells. Here we review the advances about the
interactions between joint inflammation and changes in the peri-articular
lymphatic system and discuss our view of linking "Bi" theory of CM to lymphatic
dysfunction in arthritis.
PMID- 26432789
TI - Shen (Kidney)-tonifying principle for primary osteoporosis: to treat both the
disease and the Chinese medicine syndrome.
AB - Primary osteoporosis (POP) is one of the most common diseases in the elderly
people resulting in high risk of fracture and poor quality of life. In addition
to the pathological changes in bone mass, most of the POP patients also suffer
from Chinese medicine (CM) syndromes of Shen (Kidney) essence deficiency. Shen
essences are highly related to bone. Shen essence deficiency plays an important
part in the development of POP and a better diagnosis of POP could be made by
combining CM syndromes with Western medicine risk factors. Treatments of POP
should aim at both increasing the bone mass and relieving the syndromes of Shen
essence deficiency. Clinical study confirmed that treating POP patients with Shen
tonifying herbs could increase the bone mass and relieve the CM syndromes of POP
patients. Basic researches clarified the mechanism by which Shen-tonifying herbs
increased bone mass in animal models. The mechanisms by which Shentonifying herbs
relieve the CM syndromes are still in investigation.
PMID- 26432790
TI - How personal and standardized coordination impact implementation of integrated
care.
AB - BACKGROUND: Integrating health care across specialized work units has the
potential to lower costs and increase quality and access to mental health care.
However, a key challenge for healthcare managers is how to develop policies,
procedures, and practices that coordinate care across specialized units. The
purpose of this study was to identify how organizational factors impacted
coordination, and how to facilitate implementation of integrated care. METHODS:
Semi-structured interviews were conducted in August 2009 with 30 clinic leaders
and 35 frontline staff who were recruited from a convenience sample of 16 primary
care and mental health clinics across eight medical centers. Data were drawn from
a management evaluation of primary care-mental health integration in the US
Department of Veterans Affairs. To protect informant confidentiality, the
institutional review board did not allow quotations. RESULTS: Interviews
identified antecedents of organizational coordination processes, and highlighted
how these antecedents can impact the implementation of integrated care. Overall,
implementing new workflow practices were reported to create conflicts with pre
existing standardized coordination processes. Personal coordination (i.e.,
interpersonal communication processes) between primary care leaders and staff was
reported to be effective in overcoming these barriers both by working around
standardized coordination barriers and modifying standardized procedures.
DISCUSSION: This study identifies challenges to integrated care that might be
solved with attention to personal and standardized coordination. A key finding
was that personal coordination both between primary care and mental health
leaders and between frontline staff is important for resolving barriers related
to integrated care implementation. CONCLUSION: Integrated care interventions can
involve both new standardized procedures and adjustments to existing procedures.
Aligning and integrating procedures between primary care and specialty care
requires personal coordination amongst leaders. Interpersonal relationships
should be strengthened between staff when personal connections are important for
coordinating patient care across clinical settings.
PMID- 26432791
TI - [Pavlik harness for the treatment of congenital hip dysplasia types D III and
IV].
AB - BACKGROUND: Up to 4% of all neonates in Central Europe are born with congenital
hip dysplasia (CHD), the most common congenital disease of the musculoskeletal
system. However, in this retrospective analysis the outcomes of infants with CHD
(type D, III or IV according to Graf) have been considered, with Pavlik therapy
starting within the first 12 weeks of life. Connections between the start of
therapy or the first finding according to Graf's classification and the
ultrasound result achieved, as well as the X-rays taken after 1 and 2 years, were
evaluated. No repositioning under Pavlik treatment or side effects and their
relevance have been evaluated, especially with regard to avascular necrosis (AVN)
of the femoral head. MATERIALS AND METHODS: All infants treated using Pavlik
treatment for CHD between 2010 and 2012 in our clinic were determined. A total of
62 patients with 79 pathological hips were included. The infants were classified
into three groups to evaluate the influence of the start of therapy on the
result: group I with the first investigation and start of treatment within the
first 10 days of life, group II between the 11th day and the end of week 3, group
III within preventive general examinations (U3) after the 4th week. Clinical
examinations and the usual ultrasound scans were performed at an average of 1, 3,
and 6 months. Furthermore, after 1 and 2 years clinical and radiological
investigations were carried out, as well as further examinations depending on the
findings. RESULTS: A failure of repositioning of the Pavlik treatment occurred in
group I in 1 case (2.2%), in group II in 1 case (7.1%), and in group III in 2
cases (10%). This occurs in hips type D and type III in 1 case each (3.3%) and
type IV in 2 cases (10.5%). Maturation disorders of the hips were found in 1 case
(2.2%) in group I, 1 case (7.1%) in group II, and 3 cases (15%) in group III.
Avascular necrosis of the femoral head was proven in 2 cases (4.4%) in group I,
0% in group II, and in 1 case (5%) in group III. All patients initially had
femoral head necrosis of Graf type IV . All necrosis and maturation disorders
were no longer visible on subsequent examinations after 2 years at the most.
CONCLUSIONS: In summary, the study shows that even with a late treatment start
(U3) good results could be achieved, but with a rising number of repositioning
failures and femoral necroses. Ultrasound screening on U3 seems to be sufficient;
however, for high-risk groups an additional screening in the first week of life
should be performed, which does not replace a second evaluation at U3 if there
are normal findings.
PMID- 26432792
TI - [Orthopaedic and trauma surgical care until 2050. Analysis of the utilization
behavior for relevant diseases and derivation of the number of medical service
providers].
AB - BACKGROUND: Due to current and prospective demographic developments, the
provision of high-quality medical care is not guaranteed in Germany. OBJECTIVES:
The aim of this study is to analyze the utilization of medical service providers
for diseases related to orthopedic/trauma surgery and deduce the corresponding
number of medical service providers until 2050. MATERIALS AND METHODS: Data
provided by the Statistical Offices of the Federal Republic and the Federal
States and the Scientific Institute of the AOK (2008-2012) were used to analyze
the utilization behavior of four pre-determined orthopedic/trauma surgery disease
groups (osteoarthritis, back pain, osteoporosis, trauma). Routine data of the
current (2012) health care provision delivered by the compulsory health
insurances (GKV) are the basis of the prognosis. Using population projections
from the Federal Statistical Office, the health care demand until 2050 was
predicted and using statistics from the German Medical Association, the number of
required health care providers was determined. RESULTS: An increase in physician
consultations until 2040 is expected for osteoarthritis (+ 21 %), osteoporosis
(26 %), and trauma (+ 13 %). From 2040-2050 the health care utilization behavior
of all examined diseases is expected to decrease. The increasing health care
usage behavior until 2040 is associated with an increase in health care
providers. CONCLUSIONS: Until 2030 a significant increase in the burden of
orthopedic/trauma surgery diseases is expected. In 2050 the level of health care
needs will be equivalent to that in 2030. Comprehensive needs assessment and
planning are needed in order to create health care provision structures and
processes that address potential changes in utilization behavior.
PMID- 26432793
TI - Continuous EEG Monitoring for Early Detection of Delayed Cerebral Ischemia in
Subarachnoid Hemorrhage: A Pilot Study.
AB - INTRODUCTION: Early identification of delayed cerebral ischemia (DCI) in patients
with aneurysmal subarachnoid hemorrhage (aSAH) is a major challenge. The aim of
this study was to investigate whether quantitative EEG (qEEG) features can detect
DCI prior to clinical or radiographic findings. METHODS: A prospective cohort
study was performed in aSAH patients in whom continuous EEG (cEEG) was recorded.
We studied 12 qEEG features. We compared the time point at which qEEG changed
with the time point that clinical deterioration occurred or new ischemia was
noted on CT scan. RESULTS: Twenty aSAH patients were included of whom 11
developed DCI. The alpha/delta ratio (ADR) was the most promising feature that
showed a significant difference in change over time in the DCI group (median -62%
with IQR -87 to -39%) compared to the control group (median +27% with IQR -32 to
+104%, p = 0.013). Based on the ROC curve, a threshold was chosen for a combined
measure of ADR and alpha variability (AUC: 91.7, 95% CI 74.2-100). The median
time that elapsed between change of qEEG and clinical DCI diagnosis was seven
hours (IQR -11-25). Delay between qEEG and CT scan changes was 44 h (median, IQR
14-117). CONCLUSION: In this study, ADR and alpha variability could detect DCI
development before ischemic changes on CT scan was apparent and before clinical
deterioration was noted. Implementation of cEEG in aSAH patients can probably
improve early detection of DCI.
PMID- 26432794
TI - Gibbsiella papilionis Kim et al. 2013 is a later heterotypic synonym of
Gibbsiella dentisursi Saito et al. 2013.
AB - Synonymy of Gibbsiella dentisursi DSM 23818T ( = NUM 1720T) and Gibbsiella
papilionis JCM 18389T ( = LEN33T) was suspected following multilocus sequence
analysis (MLSA) of both type strains in a previous classification study, where
they were found to share >99.6 % gene sequence similarity. The taxonomic
relationship between these two strains was re-examined here using a polyphasic
approach. A DNA-DNA hybridization value of 98 % confirmed that the two type
strains belong to a single taxon, while the phenotypic profiles were found to be
nearly identical. Therefore we propose Gibbsiella papilionis as a later
heterotypic synonym of Gibbsiella dentisursi, with the type strain as NUM 1720T (
= DSM 23818T = JCM 17201T).
PMID- 26432796
TI - Erratum to: Dosimetrics of intracranial stereotactic radiosurgery : Only "an
exercise of style"?
PMID- 26432797
TI - War and Marriage: Assortative Mating and the World War II GI Bill.
AB - World War II and its subsequent GI Bill have been widely credited with playing a
transformative role in American society, but there have been few quantitative
analyses of these historical events' broad social effects. We exploit between
cohort variation in the probability of military service to investigate how WWII
and the GI Bill altered the structure of marriage, and find that it had important
spillover effects beyond its direct effect on men's educational attainment. Our
results suggest that the additional education received by returning veterans
caused them to "sort" into wives with significantly higher levels of education.
This suggests an important mechanism by which socioeconomic status may be passed
on to the next generation.
PMID- 26432798
TI - [Communications of the Federal Association of German Pathologists: Further
education (model) curriculum, status 29 April 2015].
PMID- 26432795
TI - Control of Proliferation and Cancer Growth by the Hippo Signaling Pathway.
AB - The control of cell division is essential for normal development and the
maintenance of cellular homeostasis. Abnormal cell proliferation is associated
with multiple pathological states, including cancer. Although the Hippo/YAP
signaling pathway was initially thought to control organ size and growth,
increasing evidence indicates that this pathway also plays a major role in the
control of proliferation independent of organ size control. In particular,
accumulating evidence indicates that the Hippo/YAP signaling pathway functionally
interacts with multiple other cellular pathways and serves as a central node in
the regulation of cell division, especially in cancer cells. Here, recent
observations are highlighted that connect Hippo/YAP signaling to transcription,
the basic cell-cycle machinery, and the control of cell division. Furthermore,
the oncogenic and tumor-suppressive attributes of YAP/TAZ are reviewed, which
emphasizes the relevance of the Hippo pathway in cancer.
PMID- 26432799
TI - [Cytopathology in the diagnostics of hematological diseases].
AB - Whereas in many fields of surgical pathology examination of cytological smears
and analysis of histological tissue sections provide alternative methods which
are chosen according to the clinical requirements, in hematopathology both types
of morphological investigation are routinely applied in parallel and
simultaneously. This procedure improves the diagnostic precision and safety.
Unlike other European countries in Germany both procedures are performed by
different specialties. Cytology is the responsibility of hematologists whereas
histology is carried out by pathologists, which interferes with an integrative
diagnostic approach unless intense communication takes place. Ideally, in the
diagnosis of hematological disorders histology of bone marrow trephines should be
studied in conjunction with smears of peripheral blood and bone marrow. In many
instances, further complementary investigations, such as flow cytometry,
cytogenetics and increasingly molecular pathological studies are necessary to
guarantee an adequate modern state of diagnostics in hematopathology.
PMID- 26432800
TI - David Oliver: Why I let some patients stay longer in hospital.
PMID- 26432802
TI - DMSO Increases Mutation Scanning Detection Sensitivity of High-Resolution Melting
in Clinical Samples.
AB - BACKGROUND: Mutation scanning provides the simplest, lowest-cost method for
identifying DNA variations on single PCR amplicons, and it may be performed
before sequencing to avoid screening of noninformative wild-type samples. High
resolution melting (HRM) is the most commonly used method for mutation scanning.
With PCR-HRM, however, mutations less abundant than approximately 3%-10% that can
still be clinically significant may often be missed. Therefore, enhancing HRM
detection sensitivity is important for mutation scanning and its clinical
application. METHODS: We used serial dilution of cell lines containing the TP53
exon 8 mutation to demonstrate the improvement in detection sensitivity for
conventional-PCR-HRM in the presence of DMSO. We also conducted coamplification
at lower denaturation temperature (COLD)-PCR with an extra step for cross
hybridization, followed by preferential denaturation and amplification at
optimized critical temperature (full-COLD-PCR), to further enrich low-level
mutations before HRM with or without DMSO, and we used droplet-digital PCR to
derive the optimal conditions for mutation enrichment. Both conventional PCR-HRM
and full-COLD-PCR-HRM with and without DMSO were used for mutation scanning of
TP53 exon 8 in cancer samples containing known mutations and myelodysplastic
syndrome samples with unknown mutations. Mutations in other genes were also
examined. RESULTS: The detection sensitivity of PCR-HRM scanning increases 2- to
5-fold in the presence of DMSO, depending on mutation type and sequence context,
and can typically detect mutation abundance of approximately 1%. When mutation
enrichment is applied during amplification with full-COLD-PCR followed by HRM in
the presence of DMSO, mutations with 0.2%-0.3% abundance in TP53 exon 8 can be
detected. CONCLUSIONS: DMSO improves HRM mutation scanning sensitivity with
saturating dyes. When full-COLD-PCR is used, followed by DMSO-HRM, the overall
improvement is about 20-fold compared with conventional PCR-HRM.
PMID- 26432803
TI - Feeding on microbiomes: effects of detritivory on the taxonomic and phylogenetic
bacterial composition of animal manures.
AB - Earthworms play a key role in nutrient cycling by interacting with microorganisms
thus accelerating organic matter turnover in soil systems. As detritivores, some
earthworm types ingest and digest a mixture of dead organic matter and
microorganisms, like animal manures (i.e. animal gut microbiomes). Here we
described the earthworm cast microbiome and the role ingested bacteria play on
its composition. We fed Eisenia andrei with cow, horse and pig manures and
determined the taxonomic and phylogenetic composition of the these manures before
and after passage through the earthworm gut. Earthworm cast microbiomes showed a
smaller diversity than the manure they fed on. Manures strongly differed in their
taxonomic and phylogenetic composition, but these differences were markedly
reduced once transformed into earthworm cast microbiomes after passage through
the earthworm gut. The core earthworm cast microbiome comprised 30 OTUs (2.6% of
OTUs from cast samples), of which 10 are possibly native to the earthworm gut.
Most of the core cast microbiome OTUs belonged to phyla Actinobacteria and
Proteobacteria, as opposed to already described animal core gut microbiomes,
which are composed mainly of Firmicutes and Bacteroidetes. Our results suggest
that earthworms build up their cast microbiome by selecting from the pool of
ingested bacteria.
PMID- 26432801
TI - Menopausal Status and Abdominal Obesity Are Significant Determinants of Hepatic
Lipid Metabolism in Women.
AB - BACKGROUND: Android fat distribution (abdominal obesity) is associated with
insulin resistance, hepatic steatosis, and greater secretion of large very low
density lipoprotein (VLDL) particles in men. Since abdominal obesity is becoming
increasingly prevalent in women, we aimed to investigate the relationship between
android fat and hepatic lipid metabolism in pre- and postmenopausal women.
METHODS AND RESULTS: We used a combination of stable isotope tracer techniques to
investigate intrahepatic fatty acid synthesis and partitioning in 29 lean and 29
abdominally obese women (android fat/total fat 0.065 [0.02 to 0.08] and 0.095
[0.08 to 0.11], respectively). Thirty women were premenopausal aged 35 to 45 and
they were matched for abdominal obesity with 28 postmenopausal women aged 55 to
65. As anticipated, abdominal obese women were more insulin resistant with
enhanced hepatic secretion of large (404+/-30 versus 268+/-26 mg/kg lean mass,
P<0.001) but not small VLDL (160+/-11 versus 142+/-13). However, postmenopausal
status had a pronounced effect on the characteristics of small VLDL particles,
which were considerably triglyceride-enriched (production ratio of VLDL2-
triglyceride:apolipoprotein B 30+/-5.3 versus 19+/-1.6, P<0.05). In contrast to
postmenopausal women, there was a tight control of hepatic fatty acid metabolism
and triglyceride production in premenopausal women, whereby oxidation (rs=-0.49,
P=0.006), de novo lipogenesis (rs=0.55, P=0.003), and desaturation (rs=0.48,
P=0.012) were closely correlated with abdominal obesity-driven large VLDL
triglyceride secretion rate. CONCLUSIONS: In women, abdominal obesity is a major
driver of hepatic large VLDL particle secretion, whereas postmenopausal status
was characterized by increased small VLDL particle size. These data provide a
mechanistic basis for the hyperlipidemia observed in postmenopausal obesity.
PMID- 26432804
TI - Exploiting the fungal highway: development of a novel tool for the in situ
isolation of bacteria migrating along fungal mycelium.
AB - Fungi and bacteria form various associations that are central to numerous
environmental processes. In the so-called fungal highway, bacteria disperse along
fungal mycelium. We developed a novel tool for the in situ isolation of bacteria
moving along fungal hyphae as well as for the recovery of fungi potentially
involved in dispersal, both of which are attracted towards a target culture
medium. We present the validation and the results of the first in situ test.
Couples of fungi and bacteria were isolated from soil. Amongst the enriched
organisms, we identified several species of fast-growing fungi (Fusarium sp. and
Chaetomium sp.), as well as various potentially associated bacterial groups,
including Variovorax soli, Olivibacter soli, Acinetobacter calcoaceticus, and
several species of the genera Stenotrophomonas, Achromobacter and Ochrobactrum.
Migration of bacteria along fungal hyphae across a discontinuous medium was
confirmed in most of the cases. Although the majority of the bacteria for which
migration was confirmed were also positive for flagellar motility, not all motile
bacteria dispersed using their potential fungal partner. In addition, the
importance of hydrophobicity of the fungal mycelial surface was confirmed. Future
applications of the columns include targeting different types of microorganisms
and their interactions, either by enrichment or by state of the art molecular
biological methods.
PMID- 26432805
TI - Cercosporoid diseases of Citrus.
AB - Citrus leaves and fruits exhibiting disease symptoms ranging from greasy spot,
yellow spot, small or large brown spot, black dot, and brown dot were sampled
from Fujian, Guangdong, Guizhou, Hunan, Jiangxi, Yunnan, Zhejiang provinces and
the Guangxi Zhuang Autonomous Region in China. In total 82 isolates representing
various cercosporoid genera were isolated from these disease symptoms, which were
supplemented with eight Citrus cercosporoid isolates collected from other
countries. Based on a morphological and phylogenetic study using sequence data
from the nuclear ribosomal DNA's ITS1-5.8S-ITS2 regions (ITS), and partial actin
(act), beta-tubulin (tub2), 28S nuclear ribosomal RNA (28S rDNA) and translation
elongation factor 1-alpha (tef1) genes, these strains were placed in the
following genera: Cercospora, Pallidocercospora, Passalora, Pseudocercospora,
Verrucisporota and Zasmidium. All isolates tended to be sterile, except the
Zasmidium isolates associated with citrus greasy spot-like symptoms, which
subsequently were compared with phylogenetically similar isolates occurring on
Citrus and other hosts elsewhere. From these results four Zasmidium species were
recognized on Citrus, namely Z. indonesianum on Citrus in Indonesia, Z.
fructicola and Z. fructigenum on Citrus in China and Z. citri-griseum, which
appears to have a wide host range including Acacia, Citrus, Eucalyptus and Musa,
as well as a global distribution.
PMID- 26432806
TI - Phylogeny of Pluteus section Celluloderma including eight new species from
Brazil.
AB - A general phylogeny of Pluteus section Celluloderma based on nuc rITS1-5.8-ITS2
(ITS) barcode sequences is presented with description of eight new species from
Brazil supported by morphological and molecular data: P. brunneocrinitus, P.
cebolinhae, P. crinitus, P. halonatus, P. hispidulopsis, P. karstedtiae, P.
necopinatus and P. paucicystidiatus.
PMID- 26432807
TI - The importance of being NICE.
PMID- 26432808
TI - Factors influencing junior doctors' choices of future specialty: trends over time
and demographics based on results from UK national surveys.
AB - OBJECTIVE: To study trends in factors influencing junior doctors' choice of
future specialty. DESIGN: Respondents were asked whether each of 15 factors had a
great deal of influence on their career choice, a little influence or no
influence on it. Percentages are reported of those who specified that a factor
had a great deal of influence on their career choice. SETTING: UK. PARTICIPANTS:
A total of 15,765 UK-trained doctors who graduated between 1999 and 2012. MAIN
OUTCOME MEASURES: Questions about career choices and factors which may have
influenced those choices, in particular comparing doctors who qualified in 2008
2012 with those who qualified in 1999-2002. RESULTS: Enthusiasm for and
commitment to the specialty was a greater influence on career choice in the 2008
2012 qualifiers (81%) than those of 1999-2002 (64%), as was consideration of
their domestic circumstances (43% compared with 20%). Prospects for promotion
were less important to recent cohorts (16%) than older cohorts (21%), as were
financial prospects (respectively, 10% and 14%). Domestic circumstances and
working hours were considered more important, and financial prospects less
important, by women than men. Inclination before medical school was rated as
important by 41% of doctors who were over 30 years old, compared with 13% of
doctors who were under 21, at the time of starting medical school. CONCLUSIONS:
The increasing importance of both domestic circumstances and enthusiasm for their
specialty choice in recent cohorts suggest that today's young doctors prize both
work-life balance and personal fulfilment at work more highly than did their
predecessors. The differences in motivations of older and younger generations of
doctors, men and women, and doctors who start medical school relatively late are
worthy of note.
PMID- 26432809
TI - Tuning the heart with music.
PMID- 26432810
TI - Improving healthcare for people with dementia in England: good progress but more
to do.
PMID- 26432811
TI - Challenges of harmonising data from UK national health surveys: a case study of
attempts to estimate the UK prevalence of asthma.
PMID- 26432812
TI - Medicalisation in the UK: changing dynamics, but still ongoing.
PMID- 26432813
TI - Climate change, conflict and health.
AB - Future climate change is predicted to diminish essential natural resource
availability in many regions and perhaps globally. The resulting scarcity of
water, food and livelihoods could lead to increasingly desperate populations that
challenge governments, enhancing the risk of intra- and interstate conflict.
Defence establishments and some political scientists view climate change as a
potential threat to peace. While the medical literature increasingly recognises
climate change as a fundamental health risk, the dimension of climate change
associated conflict has so far received little attention, despite its profound
health implications. Many analysts link climate change with a heightened risk of
conflict via causal pathways which involve diminishing or changing resource
availability. Plausible consequences include: increased frequency of civil
conflict in developing countries; terrorism, asymmetric warfare, state failure;
and major regional conflicts. The medical understanding of these threats is
inadequate, given the scale of health implications. The medical and public health
communities have often been reluctant to interpret conflict as a health issue.
However, at times, medical workers have proven powerful and effective peace
advocates, most notably with regard to nuclear disarmament. The public is more
motivated to mitigate climate change when it is framed as a health issue.
Improved medical understanding of the association between climate change and
conflict could strengthen mitigation efforts and increase cooperation to cope
with the climate change that is now inevitable.
PMID- 26432814
TI - Patient perceptions and recall of consent for regional anaesthesia compared with
consent for surgery.
AB - OBJECTIVE: In Britain, consent for surgery is documented using a Department of
Health form signed by the surgeon and the patient. In contrast, anaesthetic
procedures have no formalised consent process. Evidence on the process of consent
for regional anaesthesia, and patient perceptions of this, is scarce outside
obstetric practice. We aimed to determine patient recall and perceptions of
consent for interscalene brachial plexus block and compared this to surgical
consent for shoulder arthroplasty. DESIGN: Prospective observational survey.
SETTING: A specialist musculoskeletal centre, UK. PARTICIPANTS: Forty-six
patients (female:male 30:16, mean age 61 years) undergoing shoulder arthroplasty
with interscalene brachial plexus block. MAIN OUTCOME MEASURES: Recall and
understanding of consent for regional anaesthesia and surgery was examined using
a semi-structured questionnaire 1-2 days after arthroplasty. Surgical consent
forms and discussions recorded by the anaesthetist were examined in participants'
medical notes to compare against the level of recall. Analysis to determine
statistical significance was conducted using McNemar's test. RESULTS: Recall of
surgical risks was overall significantly better than recall of brachial plexus
block risks. Compared to their recollections of surgical risk, patients
remembered fewer specific risks for brachial plexus block (p < 0.001). There were
more patients unable to recall any risks when questioned about brachial plexus
block than about their surgery (p < 0.05). One-third of patients did not regard
the consent discussion about regional anaesthesia as important as consent for
surgery and over one-quarter had not recognised the preoperative discussion about
the brachial plexus block as a consent process similar to that conducted for
surgery. CONCLUSIONS: Fundamental misunderstandings about the consent process are
prevalent. Future work in this area should seek to investigate how documentation
of the consent process and patients' understanding of consent for regional
anaesthesia can be improved.
PMID- 26432815
TI - Lessons from a modern review of the smallpox eradication files.
PMID- 26432816
TI - International trials in middle-income countries: different local scenarios
require different ethical approaches.
PMID- 26432817
TI - Has NHS reorganisation saved lives? A CuSum study using 65 years of data.
AB - OBJECTIVES: To determine if NHS reforms affect population mortality. DESIGN:
Retrospective study using routinely published data. SETTING & PARTICIPANTS:
Resident population of England and Wales 1948 to 2012 MAIN OUTCOME MEASURE: All
cause age sex directly standardised mortality England and Wales 1948 to 2012.
METHODS: Using the CuSum technique and Change-Point Analysis to identify
sustained changes in the improving age-standardised mortality rates for the
period 1948-2012, and comparing the time of these changes with periods of NHS
reform. Where observed changes did not fit with NHS reform, changes external to
the NHS were sought as a possible explanation of changes observed. RESULTS: CuSum
plotting and CPA showed no significant changes in female mortality trend between
1948 and 2012. However, this analysis identified a sustained improvement in the
male mortality trend, occurring in the mid-1970s. A further change in the rate of
male mortality decline was found around the Millennium. CONCLUSION: The 1974 NHS
reorganisation, changing service arrangements predominantly for women and
children, is considered an unlikely explanation of the improved rate of male
mortality decline. Thus, centrally led NHS reorganisation has never had any
detectable effect on either male or female mortality and must be considered
ineffective for this purpose. But some evidence supporting the view that
increased funding improves outcomes is found.
PMID- 26432819
TI - A tribute to Sjur: Sjur Olsnes, 1939-2014.
PMID- 26432818
TI - Review of the neutrophil response to Bordetella pertussis infection.
AB - The nature and timing of the neutrophil response to infection with Bordetella
pertussis is influenced by multiple virulence factors expressed by the bacterium.
After inoculation of the host airway, the recruitment of neutrophils signaled by
B. pertussis lipooligosaccharide (LOS) is suppressed by pertussis toxin (PTX).
Over the next week, the combined activities of PTX, LOS and adenylate cyclase
toxin (ACT) result in production of cytokines that generate an IL-17 response,
promoting neutrophil recruitment which peaks at 10-14 days after inoculation in
mice. Arriving at the site of infection, neutrophils encounter the powerful local
inhibitory activity of ACT, in conjunction with filamentous hemagglutinin. With
the help of antibodies, neutrophils contribute to clearance of B. pertussis, but
only after 28-35 days in a naive mouse. Studies of the lasting, antigen-specific
IL-17 response to infection in mice and baboons has led to progress in vaccine
development and understanding of pathogenesis. Questions remain about the
mediators that coordinate neutrophil recruitment and the mechanisms by which
neutrophils overcome B. pertussis virulence factors.
PMID- 26432820
TI - Health Insurance-Related Disparities in Lymphoma Survival Are Partly Mediated by
Baseline Clinical Factors.
PMID- 26432821
TI - In Reply.
PMID- 26432822
TI - Quorum quenching: role in nature and applied developments.
AB - Quorum sensing (QS) refers to the capacity of bacteria to monitor their
population density and regulate gene expression accordingly: the QS-regulated
processes deal with multicellular behaviors (e.g. growth and development of
biofilm), horizontal gene transfer and host-microbe (symbiosis and pathogenesis)
and microbe-microbe interactions. QS signaling requires the synthesis, exchange
and perception of bacterial compounds, called autoinducers or QS signals (e.g. N
acylhomoserine lactones). The disruption of QS signaling, also termed quorum
quenching (QQ), encompasses very diverse phenomena and mechanisms which are
presented and discussed in this review. First, we surveyed the QS-signal
diversity and QS-associated responses for a better understanding of the targets
of the QQ phenomena that organisms have naturally evolved and are currently
actively investigated in applied perspectives. Next the mechanisms, targets and
molecular actors associated with QS interference are presented, with a special
emphasis on the description of natural QQ enzymes and chemicals acting as QS
inhibitors. Selected QQ paradigms are detailed to exemplify the mechanisms and
biological roles of QS inhibition in microbe-microbe and host-microbe
interactions. Finally, some QQ strategies are presented as promising tools in
different fields such as medicine, aquaculture, crop production and anti
biofouling area.
PMID- 26432823
TI - Can Sonography Distinguish a Supraorbital Notch From a Foramen?
AB - Diagnostic tools for evaluating the supraorbital rim in preparation for nerve
decompression surgery in patients with chronic headaches are currently limited.
We evaluated the use of sonography to diagnose the presence of a supraorbital
notch or foramen in 11 cadaver orbits. Sonographic findings were assessed by
dissecting cadaver orbits to determine whether a notch or foramen was present.
Sonography correctly diagnosed the presence of a supraorbital notch in 7 of 7
cases and correctly diagnosed a supraorbital foramen in 4 of 4 cases. We found
that sonography had 100% sensitivity in diagnosing a supraorbital notch and
foramen. This tool may therefore be helpful in characterizing the supraorbital
rim preoperatively and may influence the decision to use a transpalpebral or
endoscopic approach for supraorbital nerve decompression as well as the decision
to use local or general anesthesia.
PMID- 26432824
TI - Wave Intensity Analysis Can Identify Eccentric Cardiac Hypertrophy in
Hypertensive Patients With Varied Left Ventricular Configurations.
AB - OBJECTIVES: The primary aim of this study was to determine whether wave intensity
can discriminate cases of eccentric hypertrophy in patients with essential
hypertension who have varied left ventricular configurations. METHODS: A total of
155 hypertensive patients with different ventricular configurations (27 normal
configuration, 42 concentric remodeling, 62 concentric hypertrophy, and 24
eccentric hypertrophy) were recruited. We performed a noninvasive wave intensity
analysis of the common carotid artery and conventional echocardiography. Blood
pressure and flow velocity were measured in the right carotid artery of all
patients. RESULTS: The left ventricular ejection fraction (LVEF) in the eccentric
hypertrophy group was significantly lower than the values in the other groups (P
< .05). The R-W1 interval/W1-W2 interval ratio (where W1 indicates the first
positive peak and W2 the second positive peak) in the eccentric hypertrophy group
was much higher than the values in the other groups (P < .05). However, there
were no significant differences in W1, W2, and negative area among these groups.
Pearson correlation analysis showed that R-W1/W1-W2, R-W1, and W1-W2were
correlated with the LVEF, whereas there was no correlation between W1, W2,
negative area, and the reflection coefficient with the LVEF. CONCLUSIONS: We
propose that by using the R-W1/W1-W2 ratio, wave intensity analysis can identify
hypertensive patients with eccentric hypertrophy without the need for
echocardiography.
PMID- 26432825
TI - Chronic Influences of Obstructive Sleep Apnea on Cerebral Venous Flow.
AB - OBJECTIVES: Evidence reveals a pathophysiologic link between sleep apnea syndrome
and cerebrovascular diseases. It is known that obstructive sleep apnea (OSA) may
cause serial hemodynamic changes and structural abnormalities in the cerebral and
cardiac arterial systems, but its effect on the cerebral venous system has
remained unclear. The purpose of this study was to compare internal jugular vein
hemodynamics between patients with OSA and healthy individuals. METHODS: Patients
with OSA and age-, body mass index-, and sex-matched healthy control participants
were recruited for a jugular venous duplex study and neurologic examination. The
luminal area of the internal jugular vein, jugular venous flow volume, time
averaged mean velocity, and presence of jugular venous reflux were recorded.
These flow characteristics were obtained at different respiratory statuses, and
we analyzed the differences between patients and controls. RESULTS: In the OSA
group, there was an increasing flow volume in total internal jugular veins at
rest. The frequency of venous reflux in patients compared with controls was
significantly decreased (26.7% versus 53.3%, respectively; P < .05). The internal
jugular vein drainage dominance was greater on the left side in the OSA group
(right versus left: 48.8% versus 51.2%), whereas it was greater on the right side
in the control group (right versus left: 61.7% versus 38.3%). CONCLUSIONS: Our
data showed peculiar internal jugular vein hemodynamics at baseline and different
respiratory statuses in patients with OSA. These characteristics imply that
cerebral venous drainage conditions might be involved in the pathophysiologic
mechanisms of OSA syndrome.
PMID- 26432826
TI - Reliability of Doppler Assessment of the Middle Cerebral Artery in the Near and
Far Fields in Healthy and Anemic Fetuses.
AB - OBJECTIVES: The purpose of this study was to assess the reliability of the middle
cerebral artery pulsatility index (PI) and peak systolic velocity (PSV) at the
proximal portions of the near- and far-field vessel sites in healthy and anemic
fetuses. METHODS: The middle cerebral artery PSV and PI were prospectively
assessed in 50 normal singleton pregnancies. The Doppler waveforms for the middle
cerebral artery PI and the PSV were recorded independently by 2 operators at the
most proximal portions of the near- and far-field sites. Data for the PSV and PI
at the proximal portions of both the near- and the far-field sites were also
retrospectively collected in 7 anemic fetuses. RESULTS: No significant difference
between the operators was detected for the middle cerebral artery PSV (P = .60)
and PI (P = .88) measured in the conventionally used near-field proximal site in
the 50 healthy fetuses. No significant difference between the proximal portions
of the near- and far-field sites was detected for the PSV (P = .53) and PI (P =
.23) in healthy or anemic fetuses. CONCLUSIONS: The findings of this study
suggest that the use of the far-field vessel is an acceptable alternative for
measurement of the middle cerebral artery PI and PSV when investigation of the
near-field vessel is technically difficult.
PMID- 26432827
TI - Ultrasound-Guided Fenestration of Tendons About the Hip and Pelvis: Clinical
Outcomes.
AB - OBJECTIVES: Percutaneous ultrasound-guided needle fenestration has been used to
treat tendinopathy of the elbow, knee, and ankle with promising results. The
purpose of this study was to evaluate the clinical outcome of ultrasound-guided
fenestration of tendons about the hip and pelvis. METHODS: After Institutional
Review Board approval, a retrospective search of imaging reports from January 1,
2005, to June 30, 2011, was completed to identify patients treated with
ultrasound-guided tendon fenestration about the hip or pelvis. Subsequent clinic
notes were retrospectively reviewed to determine whether the patient showed
marked improvement, some improvement, no change, or worsening symptoms. RESULTS:
The study group consisted of 22 tendons in 21 patients with an average age of
55.8 years (range, 26.7-77.0 years). The treated tendons included 11 gluteus
medius (9 tendinosis and 2 partial tears), 2 gluteus minimus (both tendinosis), 8
hamstring (6 tendinosis and 2 partial tears), and 1 tensor fascia latae
(tendinosis). The average interval to clinical follow-up was 70 days (range, 7
813 days). There was marked improvement in 45.5% (10 of 22), some improvement in
36.4% (8 of 22), no change in symptoms in 9.1% (2 of 22), and worsening symptoms
in 9.1% (2 of 22). There were no patient variables (age, chronicity of symptoms,
sex, tendon, tendinosis versus tear, prior physical therapy, and prior
corticosteroid injection) that were significantly different between patients who
improved and those who did not. There were no cases of a subsequent tendon tear
or infection. CONCLUSIONS: Clinical follow-up after ultrasound-guided
fenestration of the gluteus medius, gluteus minimus, proximal hamstring, and
tensor fascia latae tendons showed that 82% of patients had improvement in their
symptoms.
PMID- 26432828
TI - MaizeGDB update: new tools, data and interface for the maize model organism
database.
AB - MaizeGDB is a highly curated, community-oriented database and informatics service
to researchers focused on the crop plant and model organism Zea mays ssp. mays.
Although some form of the maize community database has existed over the last 25
years, there have only been two major releases. In 1991, the original maize
genetics database MaizeDB was created. In 2003, the combined contents of MaizeDB
and the sequence data from ZmDB were made accessible as a single resource named
MaizeGDB. Over the next decade, MaizeGDB became more sequence driven while still
maintaining traditional maize genetics datasets. This enabled the project to meet
the continued growing and evolving needs of the maize research community, yet the
interface and underlying infrastructure remained unchanged. In 2015, the MaizeGDB
team completed a multi-year effort to update the MaizeGDB resource by
reorganizing existing data, upgrading hardware and infrastructure, creating new
tools, incorporating new data types (including diversity data, expression data,
gene models, and metabolic pathways), and developing and deploying a modern
interface. In addition to coordinating a data resource, the MaizeGDB team
coordinates activities and provides technical support to the maize research
community. MaizeGDB is accessible online at http://www.maizegdb.org.
PMID- 26432829
TI - Assembly and analysis of eukaryotic Argonaute-RNA complexes in microRNA-target
recognition.
AB - Experimental studies have uncovered a variety of microRNA (miRNA)-target duplex
structures that include perfect, imperfect and seedless duplexes. However, non
canonical binding modes from imperfect/seedless duplexes are not well predicted
by computational approaches, which rely primarily on sequence and secondary
structural features, nor have their tertiary structures been characterized
because solved structures to date are limited to near perfect, straight duplexes
in Argonautes (Agos). Here, we use structural modeling to examine the role of Ago
dynamics in assembling viable eukaryotic miRNA-induced silencing complexes
(miRISCs). We show that combinations of low-frequency, global modes of motion of
Ago domains are required to accommodate RNA duplexes in model human and C.
elegans Ago structures. Models of viable miRISCs imply that Ago adopts variable
conformations at distinct target sites that generate distorted, imperfect miRNA
target duplexes. Ago's ability to accommodate a duplex is dependent on the region
where structural distortions occur: distortions in solvent-exposed seed and 3'
end regions are less likely to produce steric clashes than those in the central
duplex region. Energetic analyses of assembled miRISCs indicate that target
recognition is also driven by favorable Ago-duplex interactions. Such structural
insights into Ago loading and target recognition mechanisms may provide a more
accurate assessment of miRNA function.
PMID- 26432830
TI - MitoMiner v3.1, an update on the mitochondrial proteomics database.
AB - Mitochondrial proteins remain the subject of intense research interest due to
their implication in an increasing number of different conditions including
mitochondrial and metabolic disease, cancer, and neuromuscular degenerative and
age-related disorders. However, the mitochondrial proteome has yet to be
accurately and comprehensively defined, despite many studies. To support
mitochondrial research, we developed MitoMiner (http://mitominer.mrc
mbu.cam.ac.uk), a freely accessible mitochondrial proteomics database. MitoMiner
integrates different types of subcellular localisation evidence with protein
information from public resources, and so provides a comprehensive central
resource for data on mitochondrial protein localisation. Here we report important
updates to the database including the addition of subcellular immunofluorescent
staining results from the Human Protein Atlas, computational predictions of
mitochondrial targeting sequences, and additional large-scale mass-spectrometry
and GFP tagging data sets. This evidence is shared across the 12 species in
MitoMiner (now including Schizosaccharomyces pombe) by homology mapping.
MitoMiner provides multiple ways of querying the data including simple text
searches, predefined queries and custom queries created using the interactive
QueryBuilder. For remote programmatic access, API's are available for several
programming languages. This combination of data and flexible querying makes
MitoMiner a unique platform to investigate mitochondrial proteins, with
application in mitochondrial research and prioritising candidate mitochondrial
disease genes.
PMID- 26432831
TI - New insights into the enzymatic role of EF-G in ribosome recycling.
AB - During translation, elongation factor G (EF-G) plays a catalytic role in tRNA
translocation and a facilitative role in ribosome recycling. By stabilizing the
rotated ribosome and interacting with ribosome recycling factor (RRF), EF-G was
hypothesized to induce the domain rotations of RRF, which subsequently performs
the function of splitting the major intersubunit bridges and thus separates the
ribosome into subunits for recycling. Here, with systematic mutagenesis, FRET
analysis and cryo-EM single particle approach, we analyzed the interplay between
EF-G/RRF and post termination complex (PoTC). Our data reveal that the two
conserved loops (loop I and II) at the tip region of EF-G domain IV possess
distinct roles in tRNA translocation and ribosome recycling. Specifically, loop
II might be directly involved in disrupting the main intersubunit bridge B2a
between helix 44 (h44 from the 30S subunit) and helix 69 (H69 from the 50S
subunit) in PoTC. Therefore, our data suggest a new ribosome recycling mechanism
which requires an active involvement of EF-G. In addition to supporting RRF, EF-G
plays an enzymatic role in destabilizing B2a via its loop II.
PMID- 26432832
TI - Quadruplex formation by both G-rich and C-rich DNA strands of the C9orf72
(GGGGCC)8*(GGCCCC)8 repeat: effect of CpG methylation.
AB - Unusual DNA/RNA structures of the C9orf72 repeat may participate in repeat
expansions or pathogenesis of amyotrophic lateral sclerosis and frontotemporal
dementia. Expanded repeats are CpG methylated with unknown consequences.
Typically, quadruplex structures form by G-rich but not complementary C-rich
strands. Using CD, UV and electrophoresis, we characterized the structures formed
by (GGGGCC)8 and (GGCCCC)8 strands with and without 5-methylcytosine (5mCpG) or 5
hydroxymethylcytosine (5hmCpG) methylation. All strands formed heterogenous
mixtures of structures, with features of quadruplexes (at pH 7.5, in K(+), Na(+)
or Li(+)), but no feature typical of i-motifs. C-rich strands formed
quadruplexes, likely stabilized by G*C*G*C-tetrads and C*C*C*C-tetrads. Unlike
G*G*G*G-tetrads, some G*C*G*C-tetrad conformations do not require the N7-Guanine
position, hence C9orf72 quadruplexes still formed when N7-deazaGuanine replace
all Guanines. 5mCpG and 5hmCpG increased and decreased the thermal stability of
these structures. hnRNPK, through band-shift analysis, bound C-rich but not G
rich strands, with a binding preference of unmethylated > 5hmCpG > 5mCpG, where
methylated DNA-protein complexes were retained in the wells, distinct from
unmethylated complexes. Our findings suggest that for C-rich sequences
interspersed with G-residues, one must consider quadruplex formation and that
methylation of quadruplexes may affect epigenetic processes.
PMID- 26432833
TI - iPPI-DB: an online database of modulators of protein-protein interactions.
AB - In order to boost the identification of low-molecular-weight drugs on protein
protein interactions (PPI), it is essential to properly collect and annotate
experimental data about successful examples. This provides the scientific
community with the necessary information to derive trends about privileged
physicochemical properties and chemotypes that maximize the likelihood of
promoting a given chemical probe to the most advanced stages of development. To
this end we have developed iPPI-DB (freely accessible at
http://www.ippidb.cdithem.fr), a database that contains the structure, some
physicochemical characteristics, the pharmacological data and the profile of the
PPI targets of several hundreds modulators of protein-protein interactions. iPPI
DB is accessible through a web application and can be queried according to two
general approaches: using physicochemical/pharmacological criteria; or by
chemical similarity to a user-defined structure input. In both cases the results
are displayed as a sortable and exportable datasheet with links to external
databases such as Uniprot, PubMed. Furthermore each compound in the table has a
link to an individual ID card that contains its physicochemical and
pharmacological profile derived from iPPI-DB data. This includes information
about its binding data, ligand and lipophilic efficiencies, location in the PPI
chemical space, and importantly similarity with known drugs, and links to
external databases like PubChem, and ChEMBL.
PMID- 26432834
TI - Dynamical features of the Plasmodium falciparum ribosome during translation.
AB - Plasmodium falciparum, the mosquito-transmitted Apicomplexan parasite, causes the
most severe form of human malaria. In the asexual blood-stage, the parasite
resides within erythrocytes where it proliferates, multiplies and finally spreads
to new erythrocytes. Development of drugs targeting the ribosome, the site of
protein synthesis, requires specific knowledge of its structure and work cycle,
and, critically, the ways they differ from those in the human host. Here, we
present five cryo-electron microscopy (cryo-EM) reconstructions of ribosomes
purified from P. falciparum blood-stage schizonts at sub-nanometer resolution.
Atomic models were built from these density maps by flexible fitting.
Significantly, our study has taken advantage of new capabilities of cryo-EM, in
visualizing several structures co-existing in the sample at once, at a resolution
sufficient for building atomic models. We have discovered structural and dynamic
features that differentiate the ribosomes of P. falciparum from those of
mammalian system. Prompted by the absence of RACK1 on the ribosome in our and an
earlier study we confirmed that RACK1 does not specifically co-purify with the
80S fraction in schizonts. More extensive studies, using cryo-EM methodology, of
translation in the parasite will provide structural knowledge that may lead to
development of novel anti-malarials.
PMID- 26432836
TI - Inhibition of BMK1 pathway suppresses cancer stem cells through BNIP3 and BNIP3L.
AB - Cancer stem cells (CSCs) possess many characteristics associated with stem cells
and are believed to drive tumor initiation. Although targeting of CSCs offers
great promise for the new generation of therapeutics, lack of the effective
drugable target and appropriate pharmacological reagents significantly impedes
the development of chemotherapies. Here, we show that the phosphorylation of BMK1
was significantly correlated with not only embryonic and induced pluripotent stem
(iPS) cells, but also the CSCs. It was showed that activation of BMK1 by the
expression of MEK5D enhanced the self-renew (sphere formation), proliferation
(clone formation) and tumorigenic capacity of CSCs. While BMK1 inhibitor, XMD8
92, suppressed these capacities. RNA-seq and microarray analysis revealed that
inhibition of BMK1 significantly enhanced the expression of BNIP3 and BNIP3L,
which play important roles in cell death. Further study indicated that shRNA
mediated knock down of BNIP3 and BNIP3L impairs the BMK1 inhibitor, XMD8-92
induced suppression of sphere formation and clone formation of CSC. Collectively,
these results not only indicate that BMK1 plays an important role in maintaining
"stemness" of CSCs, but also implicate that BMK1 might be a potential drug target
for CSCs.
PMID- 26432837
TI - Cardiovascular response to thermoregulatory challenges.
AB - A growing number of extreme climate events are occurring in the setting of
ongoing climate change, with an increase in both the intensity and frequency. It
has been shown that ambient temperature challenges have a direct and highly
varied impact on cardiovascular health. With a rapidly growing amount of
literature on this issue, we aim to review the recent publications regarding the
impact of cold and heat on human populations with regard to cardiovascular
disease (CVD) mortality/morbidity while also examining lag effects, vulnerable
subgroups, and relevant mechanisms. Although the relative risk of
morbidity/mortality associated with extreme temperature varied greatly across
different studies, both cold and hot temperatures were associated with a positive
mean excess of cardiovascular deaths or hospital admissions. Cause-specific study
of CVD morbidity/mortality indicated that the sensitivity to temperature was
disease-specific, with different patterns for acute and chronic ischemic heart
disease. Vulnerability to temperature-related mortality was associated with some
characteristics of the populations, including sex, age, location, socioeconomic
condition, and comorbidities such as cardiac diseases, kidney diseases, diabetes,
and hypertension. Temperature-induced damage is thought to be related to enhanced
sympathetic reactivity followed by activation of the sympathetic nervous system,
renin-angiotensin system, as well as dehydration and a systemic inflammatory
response. Future research should focus on multidisciplinary adaptation strategies
that incorporate epidemiology, climatology, indoor/building environments, energy
usage, labor legislative perfection, and human thermal comfort models. Studies on
the underlying mechanism by which temperature challenge induces
pathophysiological response and CVD await profound and lasting investigation.
PMID- 26432838
TI - Organic cation transporter 3 contributes to norepinephrine uptake into
perivascular adipose tissue.
AB - Perivascular adipose tissue (PVAT) reduces vasoconstriction to norepinephrine
(NE). A mechanism by which PVAT could function to reduce vascular contraction is
by decreasing the amount of NE to which the vessel is exposed. PVATs from male
Sprague-Dawley rats were used to test the hypothesis that PVAT has a NE uptake
mechanism. NE was detected by HPLC in mesenteric PVAT and isolated adipocytes.
Uptake of NE (10 MUM) in mesenteric PVAT was reduced by the NE transporter (NET)
inhibitor nisoxetine (1 MUM, 73.68 +/- 7.62%, all values reported as percentages
of vehicle), the 5-hydroxytryptamine transporter (SERT) inhibitor citalopram (100
nM) with the organic cation transporter 3 (OCT3) inhibitor corticosterone (100
MUM, 56.18 +/- 5.21%), and the NET inhibitor desipramine (10 MUM) with
corticosterone (100 MUM, 61.18 +/- 6.82%). Aortic PVAT NE uptake was reduced by
corticosterone (100 MUM, 53.01 +/- 10.96%). Confocal imaging of mesenteric PVAT
stained with 4-[4-(dimethylamino)-styrl]-N-methylpyridinium iodide (ASP(+)), a
fluorescent substrate of cationic transporters, detected ASP(+) uptake into
adipocytes. ASP(+) (2 MUM) uptake was reduced by citalopram (100 nM, 66.68 +/-
6.43%), corticosterone (100 MUM, 43.49 +/- 10.17%), nisoxetine (100 nM, 84.12 +/-
4.24%), citalopram with corticosterone (100 nM and 100 MUM, respectively, 35.75
+/- 4.21%), and desipramine with corticosterone (10 and 100 MUM, respectively,
50.47 +/- 5.78%). NET protein was not detected in mesenteric PVAT adipocytes.
Expression of Slc22a3 (OCT3 gene) mRNA and protein in PVAT adipocytes was
detected by RT-PCR and immunocytochemistry, respectively. These end points
support the presence of a transporter-mediated NE uptake system within PVAT with
a potential mediator being OCT3.
PMID- 26432839
TI - A dilated cardiomyopathy mutation blunts adrenergic response and induces
contractile dysfunction under chronic angiotensin II stress.
AB - We investigated cardiac contractility in the ACTC E361G transgenic mouse model of
dilated cardiomyopathy (DCM). No differences in cardiac dimensions or systolic
function were observed in young mice, whereas young adult mice exhibited only
mild diastolic abnormalities. Dobutamine had an inotropic and lusitropic effect
on the mouse heart. In papillary muscle at 37 degrees C, dobutamine increased
relaxation rates [~50% increase of peak rate of force decline normalized to force
(dF/dtmin/F), 25% reduction of time to 90% relaxation (t90) in nontransgenic
(NTG) mice], but in the ACTC E361G mouse, dF/dtmin/F was increased 20-30%, and
t90 was only reduced 10% at 10 Hz. Pressure-volume measurements showed increases
in maximum rate of pressure decline and decreases in time constant of left
ventricular pressure decay in the ACTC E361G mouse that were 25-30% of the
changes in the NTG mouse, consistent with blunting of the lusitropic response.
The inotropic effect of dobutamine was also blunted in ACTC E361G mice, and the
dobutamine-stimulated increase in cardiac output (CO) was reduced from 2,100 to
900 MUl/min. Mice were treated with high doses of ANG II for 4 wk. The chronic
stress treatment evoked systolic dysfunction in ACTC E361G mice but not in NTG.
There was a significant reduction in rates of pressure increase and decrease, as
well as reduced end-systolic pressure and increased volume. Ejection fraction and
CO were reduced in the ACTC E361G mouse, indicating DCM. In vitro DCM-causing
mutations uncouple the relationship between Ca(2+) sensitivity and troponin I
phosphorylation. We conclude that this leads to the observed, reduced response to
beta1 agonists and reduced cardiac reserve that predisposes the heart to DCM
under conditions of chronic stress.
PMID- 26432840
TI - N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial
hypertrophic cardiomyopathy.
AB - S-glutathionylation of cardiac myosin-binding protein C (cMyBP-C) induces Ca(2+)
sensitization and a slowing of cross-bridge kinetics as a result of increased
oxidative signaling. Although there is evidence for a role of oxidative stress in
disorders associated with hypertrophic cardiomyopathy (HCM), this mechanism is
not well understood. We investigated whether oxidative myofilament modifications
may be in part responsible for diastolic dysfunction in HCM. We administered N
acetylcysteine (NAC) for 30 days to 1-mo-old wild-type mice and to transgenic
mice expressing a mutant tropomyosin (Tm-E180G) and nontransgenic littermates. Tm
E180G hearts demonstrate a phenotype similar to human HCM. After NAC
administration, the morphology and diastolic function of Tm-E180G mice was not
significantly different from controls, indicating that NAC had reversed baseline
diastolic dysfunction and hypertrophy in our model. NAC administration also
increased sarco(endo)plasmic reticulum Ca(2+) ATPase protein expression, reduced
extracellular signal-related kinase 1/2 phosphorylation, and normalized
phosphorylation of phospholamban, as assessed by Western blot. Detergent
extracted fiber bundles from NAC-administered Tm-E180G mice showed nearly
nontransgenic (NTG) myofilament Ca(2+) sensitivity. Additionally, we found that
NAC increased tension cost and rate of cross-bridge reattachment. Tm-E180G
myofilaments were found to have a significant increase in S-glutathionylation of
cMyBP-C, which was returned to NTG levels upon NAC administration. Taken
together, our results indicate that oxidative myofilament modifications are an
important mediator in diastolic function, and by relieving this modification we
were able to reverse established diastolic dysfunction and hypertrophy in HCM.
PMID- 26432841
TI - Cardiomyocyte-specific Bmal1 deletion in mice triggers diastolic dysfunction,
extracellular matrix response, and impaired resolution of inflammation.
AB - The mammalian circadian clock consists of multiple transcriptional regulators
that coordinate biological processes in a time-of-day-dependent manner.
Cardiomyocyte-specific deletion of the circadian clock component, Bmal1 (aryl
hydrocarbon receptor nuclear translocator-like protein 1), leads to age-dependent
dilated cardiomyopathy and decreased lifespan in mice. We investigated whether
cardiomyocyte-specific Bmal1 knockout (CBK) mice display early alterations in
cardiac diastolic function, extracellular matrix (ECM) remodeling, and
inflammation modulators by investigating CBK mice and littermate controls at 8
and 28 wk of age (i.e., prior to overt systolic dysfunction). Left ventricles of
CBK mice exhibited (P < 0.05): 1) progressive abnormal diastolic septal annular
wall motion and reduced pulmonary venous flow only at 28 wk of age; 2)
progressive worsening of fibrosis in the interstitial and endocardial regions
from 8 to 28 wk of age; 3) increased (>1.5 fold) expression of collagen I and
III, as well as the matrix metalloproteinases MMP-9, MMP-13, and MMP-14 at 28 wk
of age; 4) increased transcript levels of neutrophil chemotaxis and leukocyte
migration genes (Ccl2, Ccl8, Cxcl2, Cxcl1, Cxcr2, Il1beta) with no change in Il
10 and Il-13 genes expression; and 5) decreased levels of 5-LOX, HO-1 and COX-2,
enzymes indicating impaired resolution of inflammation. In conclusion, genetic
disruption of the cardiomyocyte circadian clock results in diastolic dysfunction,
adverse ECM remodeling, and proinflammatory gene expression profiles in the mouse
heart, indicating signs of early cardiac aging in CBK mice.
PMID- 26432842
TI - Effect of PDE5 inhibition on the modulation of sympathetic alpha-adrenergic
vasoconstriction in contracting skeletal muscle of young and older recreationally
active humans.
AB - Aging is associated with an altered regulation of blood flow to contracting
skeletal muscle; however, the precise mechanisms remain unclear. We recently
demonstrated that inhibition of cGMP-binding phosphodiesterase 5 (PDE5) increased
blood flow to contracting skeletal muscle of older but not young human subjects.
Here we examined whether this effect of PDE5 inhibition was related to an
improved ability to blunt alpha-adrenergic vasoconstriction (functional
sympatholysis) and/or improved efficacy of local vasodilator pathways. A group of
young (23 +/- 1 yr) and a group of older (72 +/- 1 yr) male subjects performed
knee-extensor exercise in a control setting and following intake of the highly
selective PDE5 inhibitor sildenafil. During both conditions, exercise was
performed without and with arterial tyramine infusion to evoke endogenous
norepinephrine release and consequently stimulation of alpha1- and alpha2
adrenergic receptors. The level of the sympatholytic compound ATP was measured in
venous plasma by use of the microdialysis technique. Sildenafil increased (P <
0.05) vascular conductance during exercise in the older group, but tyramine
infusion reduced (P < 0.05) this effect by 38 +/- 9%. Similarly, tyramine reduced
(P < 0.05) the vasodilation induced by arterial infusion of a nitric oxide (NO)
donor by 54 +/- 9% in the older group, and this effect was not altered by
sildenafil. Venous plasma [ATP] did not change with PDE5 inhibition in the older
subjects during exercise. Collectively, PDE5 inhibition in older humans was not
associated with an improved ability for functional sympatholysis. An improved
efficacy of the NO system may be one mechanism underlying the effect of PDE5
inhibition on exercise hyperemia in aging.
PMID- 26432843
TI - MicroRNA-145 repairs infarcted myocardium by accelerating cardiomyocyte
autophagy.
AB - We investigated whether microRNA-145 (miR-145) has a cardioprotective effect in a
rabbit model of myocardial infarction (MI) and in H9c2 rat cardiomyoblasts.
Rabbits underwent 30 min of coronary occlusion, followed by 2 days or 2 wk of
reperfusion. Control microRNA (control group; 2.5 nmol/kg, n = 10) or miR-145
(miR-145 group, 2.5 nmol/kg, n = 10) encapsulated in liposomes was intravenously
administered immediately after the start of reperfusion. H9c2 rat cardiomyoblasts
were transfected with miR-145. The MI size was significantly smaller in the miR
145 group than in the control group at 2 days and 2 wk post-MI. miR-145 had
improved the cardiac function and remodeling at 2 wk post-MI. These effects were
reversed by chloroquine. Western blot analysis showed that miR-145 accelerated
the transition of LC3B I to II and downregulated p62/SQSTM1 at 2 days or 2 wk
after MI, but not at 4 wk, and activated Akt in the ischemic area at 2 days after
MI. miR-145 inhibited the growth of H9c2 cells, accelerated the transition of
LC3B I to II, and increased phosphorylated Akt in the H9c2 cells at 2 days after
miR-145 transfection. Antagomir-145 significantly abolished the morphological
change, the transition of LC3B I to II, and the increased phosphorylated Akt
induced by miR-145 in H9c2 cells. We determined fibroblast growth factor receptor
substrate 2 mRNA to be a target of miR-145, both in an in vivo model and in H9c2
cells. In conclusion, post-MI treatment with miR-145 protected the heart through
the induction of cardiomyocyte autophagy by targeting fibroblast growth factor
receptor substrate 2.
PMID- 26432844
TI - Depressor effect of chymase inhibitor in mice with high salt-induced moderate
hypertension.
AB - The aim of the present study was to determine whether long-term high salt intake
in the drinking water induces hypertension in wild-type (WT) mice and whether a
chymase inhibitor or other antihypertensive drugs could reverse the increase of
blood pressure. Eight-week-old male WT mice were supplied with drinking water
containing 2% salt for 12 wk (high-salt group) or high-salt drinking water plus
an oral chymase inhibitor (TPC-806) at four different doses (25, 50, 75, or 100
mg/kg), captopril (75 mg/kg), losartan (100 mg/kg), hydrochlorothiazide (3
mg/kg), eplerenone (200 mg/kg), or amlodipine (6 mg/kg). Control groups were
given normal water with or without the chymase inhibitor. Blood pressure and
heart rate gradually showed a significant increase in the high-salt group,
whereas a dose-dependent depressor effect of the chymase inhibitor was observed.
There was also partial improvement of hypertension in the losartan- and
eplerenone-treated groups but not in the captopril-, hydrochlorothiazide-, and
amlodipine-treated groups. A high salt load significantly increased chymase
dependent ANG II-forming activity in the alimentary tract. In addition, the
relative contribution of chymase to ANG II formation, but not actual average
activity, showed a significant increase in skin and skeletal muscle, whereas
angiotensin-converting enzyme-dependent ANG II-forming activity and its relative
contribution were reduced by high salt intake. Plasma and urinary renin
angiotensin system components were significantly increased in the high-salt group
but were significantly suppressed in the chymase inhibitor-treated group. In
conclusion, 2% salt water drinking for 12 wk caused moderate hypertension and
activated the renin-angiotensin system in WT mice. A chymase inhibitor suppressed
both the elevation of blood pressure and heart rate, indicating a definite
involvement of chymase in salt-sensitive hypertension.
PMID- 26432845
TI - IFN-beta affects the angiogenic potential of circulating angiogenic cells by
activating calpain 1.
AB - Circulating angiogenic cells (CACs) are monocyte-derived cells with endothelial
characteristics, which contribute to both angiogenesis and arteriogenesis in a
paracrine way. Interferon-beta (IFN-beta) is known to inhibit these divergent
processes in animals and patients. We hypothesized that IFN-beta might act by
affecting the differentiation and function of CACs. CACs were cultured from
peripheral blood mononuclear cells and phenotypically characterized by surface
expression of monocytic and endothelial markers. IFN-beta significantly reduced
the number of CACs by 18-64%. Apoptosis was not induced by IFN-beta, neither in
mononuclear cells during differentiation, nor after maturation to CACs. Rather,
IFN-beta impaired adhesion to, and spreading on, fibronectin, which was dependent
on alpha5beta1 (VLA-5)-integrin. IFN-beta affected the function of VLA-5 in
mature CACs, leading to rounding and detachment of cells, by induction of calpain
1 activity. Cell rounding and detachment was completely reversed by inhibition of
calpain 1 activity in mature CACs. During in vitro capillary formation, CAC
addition and calpain 1 inhibition enhanced sprouting of endothelial cells to a
comparable extent, but were not sufficient to rescue tube formation in the
presence of IFN-beta. We show that the IFN-beta-induced reduction of the numbers
of in vitro differentiated CACs is based on activation of calpain 1, resulting in
an attenuated adhesion to extracellular matrix proteins via VLA-5. In vivo, this
could lead to inhibition of vessel formation due to reduction of the locally
recruited CAC numbers and their paracrine angiogenic factors.
PMID- 26432846
TI - Tubers are neither static nor discrete: Evidence from serial diffusion tensor
imaging.
AB - OBJECTIVE: To assess the extent and evolution of tissue abnormality of tubers,
perituber tissue, and normal-appearing white matter (NAWM) in patients with
tuberous sclerosis complex using serial diffusion tensor imaging. METHODS: We
applied automatic segmentation based on a combined global-local intensity mixture
model of 3T structural and 35 direction diffusion tensor MRIs (diffusion tensor
imaging) to define 3 regions: tuber tissue, an equal volume perituber rim, and
the remaining NAWM. For each patient, scan, lobe, and tissue type, we analyzed
the averages of mean diffusivity (MD) and fractional anisotropy (FA) in a
generalized additive mixed model. RESULTS: Twenty-five patients (mean age 5.9
years; range 0.5-24.5 years) underwent 2 to 6 scans each, totaling 70 scans.
Average time between scans was 1.2 years (range 0.4-2.9). Patient scans were
compared with those of 73 healthy controls. FA values were lowest, and MD values
were highest in tubers, next in perituber tissue, then in NAWM. Longitudinal
analysis showed a positive (FA) and negative (MD) correlation with age in tubers,
perituber tissue, and NAWM. All 3 tissue types followed a biexponential
developmental trajectory, similar to the white matter of controls. An additional
qualitative analysis showed a gradual transition of diffusion values across the
tissue type boundaries. CONCLUSIONS: Similar to NAWM, tuber and perituber tissues
in tuberous sclerosis complex undergo microstructural evolution with age. The
extent of diffusion abnormality decreases with distance to the tuber, in line
with known extension of histologic, immunohistochemical, and molecular
abnormalities beyond tuber pathology.
PMID- 26432847
TI - Dynamic tubers in tuberous sclerosis complex: A window for intervention?
PMID- 26432848
TI - Survival in synucleinopathies: A prospective cohort study.
AB - OBJECTIVES: Parkinson disease (PD), multiple system atrophy (MSA), and pure
autonomic failure (PAF) involve cytoplasmic deposition of alpha-synuclein and are
considered to be synucleinopathies. Approximately 40% of patients with PD, most
patients with MSA, and all patients with PAF have neurogenic orthostatic
hypotension (OH). This study compared long-term survival in these
synucleinopathies. METHODS: In this prospective cohort study, survival data were
obtained for 97.6% of 206 referred patients evaluated between 1994 and 2014 (47
PD + OH, 54 PD no OH, 15 cerebellar MSA [MSA-C], 57 parkinsonian MSA [MSA-P], 28
PAF). Individual diagnoses were confirmed by clinical criteria and results of
pharmacologic, neurochemical, and neuroimaging tests of sympathetic noradrenergic
innervation. The Cox proportional hazard model was used to calculate hazard
ratios (HRs) from symptom onset and from time of evaluation to death. RESULTS:
Patients with MSA-C or MSA-P had shorter survival from symptom onset than did
patients with PD + OH (age- and sex-adjusted HR = 6.1, 5.6; p < 0.0001 each), PAF
(HR = 10.8, 9.9; p < 0.0001 each) or PD no OH (HR = 14.9, 13.6; p < 0.0001 each).
Among parkinsonian patients who died, median times from motor onset to death were
7.5 years in MSA-P, 11.6 years in PD + OH, and 15.8 years in PD no OH.
Probabilities of survival for 10 years from onset of relevant symptoms were 0.39
in MSA-C, 0.33 in MSA-P, 0.74 in PD + OH, 0.87 in PAF, and 0.93 in PD no OH.
CONCLUSIONS: In synucleinopathies, survival depends on the particular disease,
with the risk of death greater in MSA-P than in PD + OH and in PD + OH than in PD
no OH.
PMID- 26432849
TI - Genetics of frontotemporal dementia in Asia: Advancing knowledge through
collaboration.
PMID- 26432850
TI - Comment: Generalizability theory and assessment in medical training.
PMID- 26432851
TI - Neurology objective structured clinical examination reliability using
generalizability theory.
AB - OBJECTIVES: This study examines factors affecting reliability, or consistency of
assessment scores, from an objective structured clinical examination (OSCE) in
neurology through generalizability theory (G theory). METHODS: Data include
assessments from a multistation OSCE taken by 194 medical students at the
completion of a neurology clerkship. Facets evaluated in this study include
cases, domains, and items. Domains refer to areas of skill (or constructs) that
the OSCE measures. G theory is used to estimate variance components associated
with each facet, derive reliability, and project the number of cases required to
obtain a reliable (consistent, precise) score. RESULTS: Reliability using G
theory is moderate (Phi coefficient = 0.61, G coefficient = 0.64). Performance is
similar across cases but differs by the particular domain, such that the majority
of variance is attributed to the domain. Projections in reliability estimates
reveal that students need to participate in 3 OSCE cases in order to increase
reliability beyond the 0.70 threshold. CONCLUSIONS: This novel use of G theory in
evaluating an OSCE in neurology provides meaningful measurement characteristics
of the assessment. Differing from prior work in other medical specialties, the
cases students were randomly assigned did not influence their OSCE score; rather,
scores varied in expected fashion by domain assessed.
PMID- 26432852
TI - Targeting semaphorins in MS as a treatment strategy to promote remyelination: A
tale of mice, rats and men.
PMID- 26432853
TI - Expression of semaphorin 3A, semaphorin 7A and their receptors in multiple
sclerosis lesions.
AB - BACKGROUND: Studies in multiple sclerosis (MS) and in experimental models point
to a critical role of semaphorin (sema)3A and sema7A in MS pathogenesis.
OBJECTIVE: The objective of this paper is to characterise the expression of
sema3A, sema7A, and their receptors in MS lesions. METHODS: We included 44
demyelinating lesions from MS patients, 12 lesions with acute cerebral infarct,
11 lesions with progressive multifocal leucoencephalopathy and 10 non
neurological control patients. MS lesions were classified according to
inflammatory activity and all samples were immunostained for sema3A, sema7A,
neuropilin 1 (Np-1), alpha1-integrin, and beta1-integrin. RESULTS: In MS-damaged
white matter sema3A and Np-1 were both detected in microglia/macrophages, whereas
reactive astrocytes expressed only sema3A. Otherwise, sema7A, alpha1-integrin and
beta1-integrin were observed in reactive astrocytes, and microglia/macrophages
only expressed beta1-integrin. The expression of sema3A, sema7A and their
receptors is more relevant in MS than in other demyelinating diseases. Sema3A and
sema7A expression correlated with the inflammatory activity of the MS lesions,
suggesting their involvement in the immunological process that takes place in MS.
CONCLUSIONS: The expression pattern of sema3A, sema7A and their receptors in MS
lesions suggests that both molecules contribute to create a negative environment
for tissue regeneration, influencing the ability to regenerate the damaged
tissue.
PMID- 26432854
TI - Grey matter involvement by focal cervical spinal cord lesions is associated with
progressive multiple sclerosis.
AB - BACKGROUND: The in vivo relationship of spinal cord lesion features with clinical
course and function in multiple sclerosis (MS) is poorly defined. OBJECTIVE: The
objective of this paper is to investigate the associations of spinal cord lesion
features on MRI with MS subgroup and disability. METHODS: We recruited 120
people: 25 clinically isolated syndrome, 35 relapsing-remitting (RR), 30
secondary progressive (SP), and 30 primary progressive (PP) MS. Disability was
measured using the Expanded Disability Status Scale. We performed 3T axial
cervical cord MRI, using 3D-fast-field-echo and phase-sensitive-inversion
recovery sequences. Both focal lesions and diffuse abnormalities were recorded.
Focal lesions were classified according to the number of white matter (WM)
columns involved and whether they extended to grey matter (GM). RESULTS: The
proportion of patients with focal lesions involving at least two WM columns and
extending to GM was higher in SPMS than in RRMS (p = 0.03) and PPMS (p = 0.015).
Diffuse abnormalities were more common in both PPMS and SPMS, compared with RRMS
(OR 6.1 (p = 0.002) and 5.7 (p = 0.003), respectively). The number of lesions per
patient involving both the lateral column and extending to GM was independently
associated with disability (p < 0.001). CONCLUSIONS: More extensive focal cord
lesions, extension of lesions to GM, and diffuse abnormalities are associated
with progressive MS and disability.
PMID- 26432855
TI - No evidence of disease activity in multiple sclerosis: Implications on cognition
and brain atrophy.
AB - BACKGROUND: The concept of no evidence of disease activity (NEDA) has emerged as
an important outcome measure for multiple sclerosis (MS). However, it is not
known if maintaining NEDA has a positive impact on cognition or brain atrophy.
OBJECTIVE: To evaluate NEDA status after two years, addressing its implications
on cognition and brain atrophy. METHODS: Forty-two relapsing-remitting MS
patients and 30 controls underwent MRI (3T) and cognitive evaluation (BRB-N).
Forty patients performed additional evaluations, after 12 and 24 months. NEDA was
defined as the absence of clinical (relapses/disability progression) and MRI
activity (new T2/gadolinium-enhancing lesions). Repeated measures and
multivariate analyses were performed to assess the contribution of NEDA criteria
to GM atrophy. RESULTS: After two years, 30.8% of the cohort had NEDA. From
these, 58.3% still had worsening in ?2 cognitive domains. Patients with MRI
activity had more cortical thinning and slightly more thalamus volume decrease.
Absence of new/enlarging T2 lesions was the only predictor of cortical thinning,
subcortical GM and thalamic atrophy rates. CONCLUSIONS: NEDA status was achieved
in a small proportion of our cohort, and did not preclude cognitive
deterioration. Absence of MRI activity and especially of new/enlarging T2 lesions
was associated with less cortical and subcortical GM atrophy.
PMID- 26432856
TI - An investigation of the relationship between latitude and multiple sclerosis
severity in New Zealand.
PMID- 26432857
TI - Monthly oral methylprednisolone pulse treatment in progressive multiple
sclerosis.
AB - BACKGROUND: There is a large unmet need for treatments for patients with
progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid
(CSF) biomarker outcomes may be well suited for the initial evaluation of
efficacious treatments. OBJECTIVE: To evaluate the effect of monthly oral
methylprednisolone pulse treatment on intrathecal inflammation in progressive MS.
METHODS: In this open-label phase 2A study, 15 primary progressive and 15
secondary progressive MS patients received oral methylprednisolone pulse
treatment for 60 weeks. Primary outcome was changes in CSF concentrations of
osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal
damage and demyelination; clinical scores; magnetic resonance imaging measures of
disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging
(DTI); motor evoked potentials; and bone density scans. RESULTS: We found no
change in the CSF concentration of osteopontin, but we observed significant
improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures.
Adverse events were well-known side effects to methylprednisolone. CONCLUSION:
Monthly methylprednisolone pulse treatment was safe, but had no effect on the
primary outcome. However, improvements in secondary clinical and MRI outcome
measures suggest that this treatment regimen may have a beneficial effect in
progressive MS.
PMID- 26432858
TI - PML risk stratification using anti-JCV antibody index and L-selectin.
AB - BACKGROUND: Natalizumab treatment is associated with progressive multifocal
leukoencephalopathy (PML) development. Treatment duration, prior
immunosuppressant use, and JCV serostatus are currently used for risk
stratification, but PML incidence stays high. Anti-JCV antibody index and L
selectin (CD62L) have been proposed as additional risk stratification parameters.
OBJECTIVE: This study aimed at verifying and integrating both parameters into one
algorithm for risk stratification. METHODS: Multicentric, international cohorts
of natalizumab-treated MS patients were assessed for JCV index (1921 control
patients and nine pre-PML patients) and CD62L (1410 control patients and 17 pre
PML patients). RESULTS: CD62L values correlate with JCV serostatus, as well as
JCV index values. Low CD62L in natalizumab-treated patients was confirmed and
validated as a biomarker for PML risk with the risk factor "CD62L low" increasing
a patient's relative risk 55-fold (p < 0.0001). Validation efforts established
86% sensitivity/91% specificity for CD62L and 100% sensitivity/59% specificity
for JCV index as predictors of PML. Using both parameters identified 1.9% of
natalizumab-treated patients in the reference center as the risk group.
CONCLUSIONS: Both JCV index and CD62L have merit for risk stratification and
share a potential biological relationship with implications for general PML
etiology. A risk algorithm incorporating both biomarkers could strongly reduce
PML incidence.
PMID- 26432859
TI - Regional cortical thinning in multiple sclerosis and its relation with cognitive
impairment: A multicenter study.
AB - OBJECTIVES: The objectives of this paper are to compare in a multicenter setting
patterns of regional cortical thickness in patients with relapsing-remitting
multiple sclerosis (RRMS) and cognitive impairment (CI) and those cognitively
preserved (CP), and explore the relationship between cortical thinning and
cognitive performance. METHODS: T1-weighted isotropic brain scans were collected
at 3T from seven European centers in 60 RRMS patients and 65 healthy controls
(HCs). Patients underwent clinical and neuropsychological examinations. Cortical
thickness (CTh) measures were calculated using FreeSurfer (failing in four) and
both lobar and vertex-based general linear model (GLM) analyses were compared
between study groups. RESULTS: Twenty (36%) MS patients were classified as CI.
Mean global CTh was smaller in RRMS patients compared to HCs (left 2.43 vs. 2.53
mm, right 2.44 vs. 2.54 mm, p < 0.001). Multivariate GLM regional analysis showed
significantly more temporal thinning in CI compared to CP patients. Verbal memory
scores correlated to regional cortical thinning in the insula whereas visual
memory scores correlated to parietal thinning. CONCLUSIONS: This multicenter
study showed mild global cortical thinning in RRMS. The extent of thinning is
less pronounced than previously reported. Only subtle regional differences
between CI and CP patients were observed, some of which related to specific
cognitive domains.
PMID- 26432860
TI - Proteomic Analysis of Microtubule Interacting Proteins over the Course of Xylem
Tracheary Element Formation in Arabidopsis.
AB - Plant vascular cells, or tracheary elements (TEs), rely on circumferential
secondary cell wall thickenings to maintain sap flow. The patterns in which TE
thickenings are organized vary according to the underlying microtubule bundles
that guide wall deposition. To identify microtubule interacting proteins present
at defined stages of TE differentiation, we exploited the synchronous
differentiation of TEs in Arabidopsis thaliana suspension cultures. Quantitative
proteomic analysis of microtubule pull-downs, using ratiometric (14)N/(15)N
labeling, revealed 605 proteins exhibiting differential accumulation during TE
differentiation. Microtubule interacting proteins associated with membrane
trafficking, protein synthesis, DNA/RNA binding, and signal transduction peaked
during secondary cell wall formation, while proteins associated with stress
peaked when approaching TE cell death. In particular, CELLULOSE SYNTHASE
INTERACTING PROTEIN1, already associated with primary wall synthesis, was
enriched during secondary cell wall formation. RNAi knockdown of genes encoding
several of the identified proteins showed that secondary wall formation depends
on the coordinated presence of microtubule interacting proteins with
nonoverlapping functions: cell wall thickness, cell wall homogeneity, and the
pattern and cortical location of the wall are dependent on different proteins.
Altogether, proteins linking microtubules to a range of metabolic compartments
vary specifically during TE differentiation and regulate different aspects of
wall patterning.
PMID- 26432861
TI - Fibrillin 5 Is Essential for Plastoquinone-9 Biosynthesis by Binding to Solanesyl
Diphosphate Synthases in Arabidopsis.
AB - Fibrillins are lipid-associated proteins in plastids and are ubiquitous in
plants. They accumulate in chromoplasts and sequester carotenoids during the
development of flowers and fruits. However, little is known about the functions
of fibrillins in leaf tissues. Here, we identified fibrillin 5 (FBN5), which is
essential for plastoquinone-9 (PQ-9) biosynthesis in Arabidopsis thaliana.
Homozygous fbn5-1 mutations were seedling-lethal, and XVE:FBN5-B transgenic
plants expressing low levels of FBN5-B had a slower growth rate and were smaller
than wild-type plants. In chloroplasts, FBN5-B specifically interacted with
solanesyl diphosphate synthases (SPSs) 1 and 2, which biosynthesize the solanesyl
moiety of PQ-9. Plants containing defective FBN5-B accumulated less PQ-9 and its
cyclized product, plastochromanol-8, but the levels of tocopherols were not
affected. The reduced PQ-9 content of XVE:FBN5-B transgenic plants was consistent
with their lower photosynthetic performance and higher levels of hydrogen
peroxide under cold stress. These results indicate that FBN5-B is required for PQ
9 biosynthesis through its interaction with SPS. Our study adds FBN5 as a
structural component involved in the biosynthesis of PQ-9. FBN5 binding to the
hydrophobic solanesyl moiety, which is generated by SPS1 and SPS2, in FBN5-B/SPS
homodimeric complexes stimulates the enzyme activity of SPS1 and SPS2.
PMID- 26432863
TI - Grasping at Straws: Unraveling the Proteome That Orchestrates Secondary Cell Wall
Patterning in Tracheary Elements.
PMID- 26432862
TI - High-Resolution Profiling of a Synchronized Diurnal Transcriptome from
Chlamydomonas reinhardtii Reveals Continuous Cell and Metabolic Differentiation.
AB - The green alga Chlamydomonas reinhardtii is a useful model organism for
investigating diverse biological processes, such as photosynthesis and
chloroplast biogenesis, flagella and basal body structure/function, cell growth
and division, and many others. We combined a highly synchronous photobioreactor
culture system with frequent temporal sampling to characterize genome-wide
diurnal gene expression in Chlamydomonas. Over 80% of the measured transcriptome
was expressed with strong periodicity, forming 18 major clusters. Genes
associated with complex structures and processes, including cell cycle control,
flagella and basal bodies, ribosome biogenesis, and energy metabolism, all had
distinct signatures of coexpression with strong predictive value for assigning
and temporally ordering function. Importantly, the frequent sampling regime
allowed us to discern meaningful fine-scale phase differences between and within
subgroups of genes and enabled the identification of a transiently expressed
cluster of light stress genes. Coexpression was further used both as a data
mining tool to classify and/or validate genes from other data sets related to the
cell cycle and to flagella and basal bodies and to assign isoforms of duplicated
enzymes to their cognate pathways of central carbon metabolism. Our diurnal
coexpression data capture functional relationships established by dozens of prior
studies and are a valuable new resource for investigating a variety of biological
processes in Chlamydomonas and other eukaryotes.
PMID- 26432865
TI - High-mobility group box 1 promotes extracellular matrix synthesis and wound
repair in human bronchial epithelial cells.
AB - High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP)
protein that binds Toll-like receptors (e.g., TLR4) and the receptor for advanced
glycated end products (RAGE). The direct effects of HMGB1 on airway structural
cells are not fully known. As epithelial cell responses are fundamental drivers
of asthma, including abnormal repair-restitution linked to changes in
extracellular matrix (ECM) synthesis, we tested the hypothesis that HMGB1
promotes bronchial epithelial cell wound repair via TLR4 and/or RAGE signaling
that regulates ECM (fibronectin and the gamma2-chain of laminin-5) and integrin
protein abundance. To assess impact of HMGB1 we used molecular and
pharmacological inhibitors of RAGE or TLR4 signaling in scratch wound,
immunofluorescence, and immunoblotting assays to assess wound repair, ECM
synthesis, and phosphorylation of intracellular signaling. HMGB1 increased wound
closure, and this effect was attenuated by blocking RAGE and TLR4 signaling.
HMGB1-induced fibronectin and laminin-5 (gamma2 chain) was diminished by blocking
RAGE and/or blunting TLR4 signaling. Similarly, induction of alpha3-integrin
receptor for fibronectin and laminin-5 was also diminished by blocking TLR4
signaling and RAGE. Lastly, rapid and/or sustained phosphorylation of SMAD2,
ERK1/2, and JNK signaling modulated HMGB1-induced wound closure. Our findings
suggest a role for HMGB1 in human airway epithelial cell repair and restitution
via multiple pathways mediated by TLR4 and RAGE that underpin increased ECM
synthesis and modulation of cell-matrix adhesion.
PMID- 26432864
TI - Imatinib attenuates inflammation and vascular leak in a clinically relevant two
hit model of acute lung injury.
AB - Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), an illness
characterized by life-threatening vascular leak, is a significant cause of
morbidity and mortality in critically ill patients. Recent preclinical studies
and clinical observations have suggested a potential role for the
chemotherapeutic agent imatinib in restoring vascular integrity. Our prior work
demonstrates differential effects of imatinib in mouse models of ALI, namely
attenuation of LPS-induced lung injury but exacerbation of ventilator-induced
lung injury (VILI). Because of the critical role of mechanical ventilation in the
care of patients with ARDS, in the present study we pursued an assessment of the
effectiveness of imatinib in a "two-hit" model of ALI caused by combined LPS and
VILI. Imatinib significantly decreased bronchoalveolar lavage protein, total
cells, neutrophils, and TNF-alpha levels in mice exposed to LPS plus VILI,
indicating that it attenuates ALI in this clinically relevant model. In
subsequent experiments focusing on its protective role in LPS-induced lung
injury, imatinib attenuated ALI when given 4 h after LPS, suggesting potential
therapeutic effectiveness when given after the onset of injury. Mechanistic
studies in mouse lung tissue and human lung endothelial cells revealed that
imatinib inhibits LPS-induced NF-kappaB expression and activation. Overall, these
results further characterize the therapeutic potential of imatinib against
inflammatory vascular leak.
PMID- 26432866
TI - Protective effects of surfactant protein D treatment in 1,3-beta-glucan-modulated
allergic inflammation.
AB - Surfactant protein D (SP-D) is a pulmonary collectin important in lung immunity.
SP-D-deficient mice (Sftpd(-/-)) are reported to be susceptible to ovalbumin
(OVA)- and fungal allergen-induced pulmonary inflammation, while treatment with
exogenous SP-D has therapeutic effects in such disease models. beta-Glucans are a
diverse group of polysaccharides previously suggested to serve as fungal ligands
for SP-D. We set out to investigate if SP-D could interact with 1,3-beta-glucan
and attenuate allergic pulmonary inflammation in the presence of 1,3-beta-glucan.
Allergic airway disease was induced in Sftpd(-/-) and Sftpd(+/+) mice by OVA
sensitization and subsequent challenge with OVA, 1,3-beta-glucan, or OVA/1,3-beta
glucan together. Mice in the combined treatment group were further treated with a
high dose of recombinant fragment of human SP-D (rfhSP-D). We demonstrated direct
interaction between SP-D and 1,3-beta-glucan. OVA-induced mucous cell metaplasia
was increased in Sftpd(-/-) mice, supporting previously reported protective
effects of endogenous SP-D in allergy. OVA-induced parenchymal CCL11 levels and
eosinophilic infiltration in bronchoalveolar lavage were unaffected by 1,3-beta
glucan, but were reversed with rfhSP-D treatment. 1,3-beta-Glucan treatment did,
however, induce pulmonary neutrophilic infiltration and increased TNF-alpha
levels in bronchoalveolar lavage, independently of OVA-induced allergy. This
infiltration was also reversed by treatment with rfhSP-D. 1,3-beta-Glucan reduced
OVA-induced mucous cell metaplasia, T helper 2 cytokines, and IFN-gamma
production. rfhSP-D treatment further reduced mucous metaplasia and T helper 2
cytokine secretion to background levels. In summary, rfhSP-D treatment resulted
in attenuation of both allergic inflammation and 1,3-beta-glucan-mediated
neutrophilic inflammation. Our data suggest that treatment with high-dose SP-D
protects from mold-induced exacerbations of allergic asthma.
PMID- 26432867
TI - Ecto-5'-nucleotidase CD73 modulates the innate immune response to influenza
infection but is not required for development of influenza-induced acute lung
injury.
AB - Extracellular nucleotides and nucleosides are important signaling molecules in
the lung. Nucleotide and nucleoside concentrations in alveolar lining fluid are
controlled by a complex network of surface ectonucleotidases. Previously, we
demonstrated that influenza A/WSN/33 (H1N1) virus resulted in increased levels of
the nucleotide ATP and the nucleoside adenosine in bronchoalveolar lavage fluid
(BALF) of wild-type (WT) C57BL/6 mice. Influenza-induced acute lung injury (ALI)
was highly attenuated in A1-adenosine receptor-knockout mice. Because AMP
hydrolysis by the ecto-5'-nucleotidase (CD73) plays a central role in and is rate
limiting for generation of adenosine in the normal lung, we hypothesized that ALI
would be attenuated in C57BL/6-congenic CD73-knockout (CD73-KO) mice. Infection
induced hypoxemia, bradycardia, viral replication, and bronchoconstriction were
moderately increased in CD73-KO mice relative to WT controls. However,
postinfection weight loss, pulmonary edema, and parenchymal dysfunction were not
altered. Treatment of WT mice with the CD73 inhibitor 5'-(alpha,beta-methylene)
diphosphate (APCP) also had no effect on infection-induced pulmonary edema but
modestly attenuated hypoxemia. BALF from CD73-KO and APCP-treated WT mice
contained more IL-6 and CXCL-10/IFN-gamma-induced protein 10, less CXCL
1/keratinocyte chemoattractant, and fewer neutrophils than BALF from untreated WT
controls. BALF from APCP-treated WT mice also contained fewer alveolar
macrophages and more transforming growth factor-beta than BALF from untreated WT
mice. These results indicate that CD73 is not necessary for development of ALI
following influenza A virus infection and suggest that tissue-nonspecific
alkaline phosphatase may be responsible for increased adenosine generation in the
infected lung. However, they do suggest that CD73 has a previously unrecognized
immunomodulatory role in influenza.
PMID- 26432868
TI - An oxidative DNA "damage" and repair mechanism localized in the VEGF promoter is
important for hypoxia-induced VEGF mRNA expression.
AB - In hypoxia, mitochondria-generated reactive oxygen species not only stimulate
accumulation of the transcriptional regulator of hypoxic gene expression, hypoxia
inducible factor-1 (Hif-1), but also cause oxidative base modifications in
hypoxic response elements (HREs) of hypoxia-inducible genes. When the hypoxia
induced base modifications are suppressed, Hif-1 fails to associate with the HRE
of the VEGF promoter, and VEGF mRNA accumulation is blunted. The mechanism
linking base modifications to transcription is unknown. Here we determined
whether recruitment of base excision DNA repair (BER) enzymes in response to
hypoxia-induced promoter modifications was required for transcription complex
assembly and VEGF mRNA expression. Using chromatin immunoprecipitation analyses
in pulmonary artery endothelial cells, we found that hypoxia-mediated formation
of the base oxidation product 8-oxoguanine (8-oxoG) in VEGF HREs was temporally
associated with binding of Hif-1alpha and the BER enzymes 8-oxoguanine
glycosylase 1 (Ogg1) and redox effector factor-1 (Ref-1)/apurinic/apyrimidinic
endonuclease 1 (Ape1) and introduction of DNA strand breaks. Hif-1alpha
colocalized with HRE sequences harboring Ref-1/Ape1, but not Ogg1. Inhibition of
BER by small interfering RNA-mediated reduction in Ogg1 augmented hypoxia-induced
8-oxoG accumulation and attenuated Hif-1alpha and Ref-1/Ape1 binding to VEGF HRE
sequences and blunted VEGF mRNA expression. Chromatin immunoprecipitation
sequence analysis of 8-oxoG distribution in hypoxic pulmonary artery endothelial
cells showed that most of the oxidized base was localized to promoters with
virtually no overlap between normoxic and hypoxic data sets. Transcription of
genes whose promoters lost 8-oxoG during hypoxia was reduced, while those gaining
8-oxoG was elevated. Collectively, these findings suggest that the BER pathway
links hypoxia-induced introduction of oxidative DNA modifications in promoters of
hypoxia-inducible genes to transcriptional activation.
PMID- 26432869
TI - Pharmacological targeting of VEGFR signaling with axitinib inhibits Tsc2-null
lesion growth in the mouse model of lymphangioleiomyomatosis.
AB - Pulmonary lymphangioleiomyomatosis (LAM), a rare progressive lung disease
associated with mutations of the tuberous sclerosis complex 2 (Tsc2) tumor
suppressor gene, manifests by neoplastic growth of LAM cells, induction of cystic
lung destruction, and respiratory failure. LAM severity correlates with
upregulation in serum of the prolymphangiogenic vascular endothelial growth
factor D (VEGF-D) that distinguishes LAM from other cystic diseases. The goals of
our study was to determine whether Tsc2 deficiency upregulates VEGF-D, and
whether axitinib, the Food and Drug Administration-approved small-molecule
inhibitor of VEGF receptor (VEGFR) signaling, will reduce Tsc2-null lung lesion
growth in a mouse model of LAM. Our data demonstrate upregulation of VEGF-D in
the serum and lung lining in mice with Tsc2-null lesions. Progressive growth of
Tsc2-null lesions induces recruitment and activation of inflammatory cells and
increased nitric oxide production. Recruited cells isolated from the lung lining
of mice with Tsc2-null lesions demonstrate upregulated expression of
provasculogenic Vegfa, prolymphangiogenic Figf, and proinflammatory Nos2, Il6,
and Ccl2 genes. Importantly, axitinib is an effective inhibitor of Tsc2-null
lesion growth and inflammatory cell recruitment, which correlates with reduced
VEGF-D levels in serum and lung lining. Our data demonstrate that pharmacological
inhibition of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth,
attenuates recruitment and activation of inflammatory cells, and reduces VEGF-D
levels systemically and in the lung lining. Our study suggests a potential
therapeutic benefit of inhibition of VEGFR signaling for treatment of LAM.
PMID- 26432870
TI - Homeostasis and its disruption in the lung microbiome.
AB - The disciplines of physiology and ecology are united by the shared centrality of
the concept of homeostasis: the stability of a complex system via internal
mechanisms of self-regulation, resilient to external perturbation. In the past
decade, these fields of study have been bridged by the discovery of the lung
microbiome. The respiratory tract, long considered sterile, is in fact a dynamic
ecosystem of microbiota, intimately associated with the host inflammatory
response, altered in disease states. If the microbiome is a "newly discovered
organ," ecology is the language we use to explain how it establishes, maintains,
and loses homeostasis. In this essay, we review recent insights into the feedback
mechanisms by which the lung microbiome and the host response are regulated in
health and dysregulated in acute and chronic lung disease. We propose three
explanatory models supported by recent studies: the adapted island model of lung
biogeography, nutritional homeostasis at the host-microbiome interface, and
interkingdom signaling and the community stress response.
PMID- 26432873
TI - Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic
lung disease.
AB - Supplemental oxygen after premature birth results in aberrant airway, alveolar,
and pulmonary vascular development with an increased risk for bronchopulmonary
dysplasia, and development of wheeze and asthma, pulmonary hypertension, and
chronic obstructive pulmonary disease in survivors. Although stimulation of the
nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP signal transduction
pathway has significant beneficial effects on disease development in animal
models, so far this could not be translated to the clinic. Oxidative stress
reduces the NO-sGC-cGMP pathway by oxidizing heme-bound sGC, resulting in
inactivation or degradation of sGC. Reduced sGC activity and/or expression is
associated with pathology due to premature birth, oxidative stress-induced lung
injury, including impaired alveolar maturation, smooth muscle cell (SMC)
proliferation and contraction, impaired airway relaxation and vasodilation,
inflammation, pulmonary hypertension, right ventricular hypertrophy, and an
aggravated response toward hyperoxia-induced neonatal lung injury. Recently,
Britt et al. (10) demonstrated that histamine-induced Ca(2+) responses were
significantly elevated in hyperoxia-exposed fetal human airway SMCs compared with
normoxic controls and that this hyperoxia-induced increase in the response was
strongly reduced by NO-independent stimulation and activation of sGC. These
recent studies highlight the therapeutic potential of sGC modulators in the
treatment of preterm infants for respiratory distress with supplemental oxygen.
Such treatment is aimed at improving aberrant alveolar and vascular development
of the neonatal lung and preventing the development of wheezing and asthma in
survivors of premature birth. In addition, these studies highlight the
suitability of fetal human airway SMCs as a translational model for pathological
airway changes in the neonate.
PMID- 26432871
TI - ncRNA-regulated immune response and its role in inflammatory lung diseases.
AB - Despite the greatly expanded knowledge on the regulation of immune response by
protein molecules, there is increasing understanding that noncoding RNAs (ncRNAs)
are also an integral component of this regulatory network. Abnormal immune
response serves a central role in the initiation, progression, and exacerbation
of inflammatory lung diseases, such as asthma, chronic obstructive pulmonary
disease, cystic fibrosis, and acute respiratory distress syndrome/acute lung
injury. Dysregulation of ncRNAs has been linked to various immunopathologies. In
this review, we highlighted the role of ncRNAs in the regulation of innate and
adaptive immunity and summarized recent findings that ncRNAs participate in the
pathogenesis of inflammatory lung diseases via their regulation of pulmonary
immunity. We also discussed therapeutic potentials for targeting ncRNAs to treat
these lung disorders.
PMID- 26432874
TI - Estimation of the number of alveolar capillaries by the Euler number (Euler
Poincare characteristic).
AB - The lung parenchyma provides a maximal surface area of blood-containing
capillaries that are in close contact with a large surface area of the air
containing alveoli. Volume and surface area of capillaries are the classic
stereological parameters to characterize the alveolar capillary network (ACN) and
have provided essential structure-function information of the lung. When loss
(rarefaction) or gain (angiogenesis) of capillaries occurs, these parameters may
not be sufficient to provide mechanistic insight. Therefore, it would be
desirable to estimate the number of capillaries, as it contains more distinct and
mechanistically oriented information. Here, we present a new stereological method
to estimate the number of capillary loops in the ACN. One advantage of this
method is that it is independent of the shape, size, or distribution of the
capillaries. We used consecutive, 1 MUm-thick sections from epoxy resin-embedded
material as a physical disector. The Euler-Poincare characteristic of capillary
networks can be estimated by counting the easily recognizable topological
constellations of "islands," "bridges," and "holes." The total number of
capillary loops in the ACN can then be calculated from the Euler-Poincare
characteristic. With the use of the established estimator of alveolar number, it
is possible to obtain the mean number of capillary loops per alveolus. In
conclusion, estimation of alveolar capillaries by design-based stereology is an
efficient and unbiased method to characterize the ACN and may be particularly
useful for studies on emphysema, pulmonary hypertension, or lung development.
PMID- 26432872
TI - Role of epithelial sodium channels in the regulation of lung fluid homeostasis.
AB - In utero, fetal lung epithelial cells actively secrete Cl(-) ions into the lung
air spaces while Na(+) ions follow passively to maintain electroneutrality. This
process, driven by an electrochemical gradient generated by the Na(+)-K(+)
ATPase, is responsible for the secretion of fetal fluid that is essential for
normal lung development. Shortly before birth, a significant upregulation of
amiloride-sensitive epithelial channels (ENaCs) on the apical side of the lung
epithelial cells results in upregulation of active Na(+) transport. This process
is critical for the reabsorption of fetal lung fluid and the establishment of
optimum gas exchange. In the adult lung, active Na(+) reabsorption across distal
lung epithelial cells limits the degree of alveolar edema in patients with acute
lung injury and cardiogenic edema. Cl(-) ions are transported either
paracellularly or transcellularly to preserve electroneutrality. An increase in
Cl(-) secretion across the distal lung epithelium has been reported following an
acute increase in left atrial pressure and may result in pulmonary edema. In
contrast, airway epithelial cells secrete Cl(-) through apical cystic fibrosis
transmembrane conductance regulator and Ca(2+)-activated Cl(-) channels and
absorb Na(+). Thus the coordinated action of Cl(-) secretion and Na(+) absorption
is essential for maintenance of the volume of epithelial lining fluid that, in
turn, maximizes mucociliary clearance and facilitates clearance of bacteria and
debris from the lungs. Any factor that interferes with Na(+) or Cl(-) transport
or dramatically upregulates ENaC activity in airway epithelial cells has been
associated with lung diseases such as cystic fibrosis or chronic obstructive lung
disease. In this review we focus on the role of the ENaC, the mechanisms involved
in ENaC regulation, and how ENaC dysregulation can lead to lung pathology.
PMID- 26432875
TI - PBL13 Is a Serine/Threonine Protein Kinase That Negatively Regulates Arabidopsis
Immune Responses.
AB - Receptor-like cytoplasmic kinases (RLCKs) are a subset of plant receptor-like
kinases lacking both extracellular and transmembrane domains. Some of the 46
members in the Arabidopsis (Arabidopsis thaliana) RLCK subfamily VII have been
linked to plant innate immunity; however, most remain uncharacterized. Thus,
multiple subfamily VII members are expected to be involved in plant immune
signaling. Here, we investigate the role of AvrPphB SUSCEPTIBLE1-LIKE13 (PBL13),
a subfamily VII RLCK with unique domain architecture. Unlike other characterized
RLCKs, PBL13 transfer DNA insertion lines exhibit enhanced disease resistance
after inoculation with virulent Pseudomonas syringae. The pbl13-2 knockout also
exhibits elevated basal-level expression of the PATHOGENESIS-RELATED GENE1
defense marker gene, enhanced reactive oxygen species (ROS) burst in response to
perception of bacterial microbial patterns, and accelerated flagellin-induced
activation of mitogen-activated protein kinases. Recombinant PBL13 is an active
kinase, and its primary autophosphorylated sites map to a 15-amino acid repeat
motif unique to PBL13. Complementation of pbl13-2 with PBL13-3xFLAG converts the
enhanced resistance and elevated ROS phenotypes back to wild-type levels. In
contrast, kinase-dead PBL13(K111A)-3xFLAG was unable to rescue pbl13-2 disease
phenotypes. Consistent with the enhanced ROS burst in the pbl13-2 knockout, PBL13
is able to associate with the nicotinamide adenine dinucleotide phosphate,
reduced oxidase RESPIRATORY BURST OXIDASE HOMOLOG PROTEIN D (RBOHD) by split
luciferase complementation assay, and this association is disrupted by flagellin
treatment. We conclude that the PBL13 kinase negatively regulates plant innate
immunity to pathogenic bacteria and can associate with RBOHD before pathogen
perception. These data are consistent with the hypothesis that PBL13 acts to
prevent inappropriate activation of defense responses in the absence of pathogen
challenge.
PMID- 26432876
TI - Variability and Constancy in Cellular Growth of Arabidopsis Sepals.
AB - Growth of tissues is highly reproducible; yet, growth of individual cells in a
tissue is highly variable, and neighboring cells can grow at different rates. We
analyzed the growth of epidermal cell lineages in the Arabidopsis (Arabidopsis
thaliana) sepal to determine how the growth curves of individual cell lineages
relate to one another in a developing tissue. To identify underlying growth
trends, we developed a continuous displacement field to predict spatially
averaged growth rates. We showed that this displacement field accurately
describes the growth of sepal cell lineages and reveals underlying trends within
the variability of in vivo cellular growth. We found that the tissue, individual
cell lineages, and cell walls all exhibit growth rates that are initially low,
accelerate to a maximum, and decrease again. Accordingly, these growth curves can
be represented by sigmoid functions. We examined the relationships among the cell
lineage growth curves and surprisingly found that all lineages reach the same
maximum growth rate relative to their size. However, the cell lineages are not
synchronized; each cell lineage reaches this same maximum relative growth rate
but at different times. The heterogeneity in observed growth results from
shifting the same underlying sigmoid curve in time and scaling by size. Thus,
despite the variability in growth observed in our study and others, individual
cell lineages in the developing sepal follow similarly shaped growth curves.
PMID- 26432877
TI - GmEXPB2, a Cell Wall beta-Expansin, Affects Soybean Nodulation through Modifying
Root Architecture and Promoting Nodule Formation and Development.
AB - Nodulation is an essential process for biological nitrogen (N2) fixation in
legumes, but its regulation remains poorly understood. Here, a beta-expansin
gene, GmEXPB2, was found to be critical for soybean (Glycine max) nodulation.
GmEXPB2 was preferentially expressed at the early stage of nodule development.
beta-Glucuronidase staining further showed that GmEXPB2 was mainly localized to
the nodule vascular trace and nodule vascular bundles, as well as nodule cortical
and parenchyma cells, suggesting that GmEXPB2 might be involved in cell wall
modification and extension during nodule formation and development.
Overexpression of GmEXPB2 dramatically modified soybean root architecture,
increasing the size and number of cortical cells in the root meristematic and
elongation zones and expanding root hair density and size of the root hair zone.
Confocal microscopy with green fluorescent protein-labeled rhizobium USDA110
cells showed that the infection events were significantly enhanced in the GmEXPB2
overexpressing lines. Moreover, nodule primordium development was earlier in
overexpressing lines compared with wild-type plants. Thereby, overexpression of
GmEXPB2 in either transgenic soybean hairy roots or whole plants resulted in
increased nodule number, nodule mass, and nitrogenase activity and thus elevated
plant N and phosphorus content as well as biomass. In contrast, suppression of
GmEXPB2 in soybean transgenic composite plants led to smaller infected cells and
thus reduced number of big nodules, nodule mass, and nitrogenase activity,
thereby inhibiting soybean growth. Taken together, we conclude that GmEXPB2
critically affects soybean nodulation through modifying root architecture and
promoting nodule formation and development and subsequently impacts biological N2
fixation and growth of soybean.
PMID- 26432879
TI - Activated OCP unlocks nonphotochemical quenching in cyanobacteria.
PMID- 26432878
TI - A Phylogenetically Conserved Group of Nuclear Factor-Y Transcription Factors
Interact to Control Nodulation in Legumes.
AB - The endosymbiotic association between legumes and soil bacteria called rhizobia
leads to the formation of a new root-derived organ called the nodule in which
differentiated bacteria convert atmospheric nitrogen into a form that can be
assimilated by the host plant. Successful root infection by rhizobia and nodule
organogenesis require the activation of symbiotic genes that are controlled by a
set of transcription factors (TFs). We recently identified Medicago truncatula
nuclear factor-YA1 (MtNF-YA1) and MtNF-YA2 as two M. truncatula TFs playing a
central role during key steps of the Sinorhizobium meliloti-M. truncatula
symbiotic interaction. NF-YA TFs interact with NF-YB and NF-YC subunits to
regulate target genes containing the CCAAT box consensus sequence. In this study,
using a yeast two-hybrid screen approach, we identified the NF-YB and NF-YC
subunits able to interact with MtNF-YA1 and MtNF-YA2. In yeast (Saccharomyces
cerevisiae) and in planta, we further demonstrated by both coimmunoprecipitation
and bimolecular fluorescence complementation that these NF-YA, -B, and -C
subunits interact and form a stable NF-Y heterotrimeric complex. Reverse genetic
and chromatin immunoprecipitation-PCR approaches revealed the importance of these
newly identified NF-YB and NF-YC subunits for rhizobial symbiosis and binding to
the promoter of MtERN1 (for Ethylene Responsive factor required for Nodulation),
a direct target gene of MtNF-YA1 and MtNF-YA2. Finally, we verified that a
similar trimer is formed in planta by the common bean (Phaseolus vulgaris) NF-Y
subunits, revealing the existence of evolutionary conserved NF-Y protein
complexes to control nodulation in leguminous plants. This sheds light on the
process whereby an ancient heterotrimeric TF mainly controlling cell division in
animals has acquired specialized functions in plants.
PMID- 26432880
TI - Control of cerebellar granule cell output by sensory-evoked Golgi cell
inhibition.
AB - Classical feed-forward inhibition involves an excitation-inhibition sequence that
enhances the temporal precision of neuronal responses by narrowing the window for
synaptic integration. In the input layer of the cerebellum, feed-forward
inhibition is thought to preserve the temporal fidelity of granule cell spikes
during mossy fiber stimulation. Although this classical feed-forward inhibitory
circuit has been demonstrated in vitro, the extent to which inhibition shapes
granule cell sensory responses in vivo remains unresolved. Here we combined whole
cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to
directly assess the impact of Golgi cell inhibition on sensory information
transmission in the granule cell layer of the cerebellum. We show that the
majority of granule cells in Crus II of the cerebrocerebellum receive sensory
evoked phasic and spillover inhibition prior to mossy fiber excitation. This
preceding inhibition reduces granule cell excitability and sensory-evoked spike
precision, but enhances sensory response reproducibility across the granule cell
population. Our findings suggest that neighboring granule cells and Golgi cells
can receive segregated and functionally distinct mossy fiber inputs, enabling
Golgi cells to regulate the size and reproducibility of sensory responses.
PMID- 26432882
TI - Correction for Petersen et al., Effect of aging on muscle mitochondrial substrate
utilization in humans.
PMID- 26432883
TI - Reply to Berti: Relationship between production and consumption diversity remains
small also with modified diversity measures.
PMID- 26432881
TI - How grow-and-switch gravitropism generates root coiling and root waving growth
responses in Medicago truncatula.
AB - Experimental studies show that plant root morphologies can vary widely from
straight gravity-aligned primary roots to fractal-like root architectures.
However, the opaqueness of soil makes it difficult to observe how environmental
factors modulate these patterns. Here, we combine a transparent hydrogel growth
medium with a custom built 3D laser scanner to directly image the morphology of
Medicago truncatula primary roots. In our experiments, root growth is obstructed
by an inclined plane in the growth medium. As the tilt of this rigid barrier is
varied, we find Medicago transitions between randomly directed root coiling,
sinusoidal root waving, and normal gravity-aligned morphologies. Although these
root phenotypes appear morphologically distinct, our analysis demonstrates the
divisions are less well defined, and instead, can be viewed as a 2D biased random
walk that seeks the path of steepest decent along the inclined plane. Features of
this growth response are remarkably similar to the widely known run-and-tumble
chemotactic behavior of Escherichia coli bacteria, where biased random walks are
used as optimal strategies for nutrient uptake.
PMID- 26432884
TI - Relationship between production diversity and dietary diversity depends on how
number of foods is counted.
PMID- 26432885
TI - Both ciliary and non-ciliary functions of Foxj1a confer Wnt/beta-catenin
signaling in zebrafish left-right patterning.
AB - The Wnt/beta-catenin pathway is implicated in left-right (LR) axis determination;
however, the underlying mechanism remains elusive. Prompted by our recent
discovery that Wnt signaling regulates ciliogenesis in the zebrafish Kupffer's
vesicle (KV) via Foxj1a, a ciliogenic transcription factor, we decided to
elucidate functions of Foxj1a in Wnt-regulated LR pattern formation. We showed
that targeted injection of wnt8a mRNA into a single cell at the 128-cell stage is
sufficient to induce ectopic foxj1a expression and ectopic cilia. By
interrogating the transcription circuit of foxj1a regulation, we found that both
Lef1 and Tcf7 bind to a consensus element in the foxj1a promoter region.
Depletion of Lef1 and Tcf7 inhibits foxj1a transcription in the dorsal forerunner
cells, downregulates cilia length and number in KV, and randomizes LR asymmetry.
Targeted overexpression of a constitutively active form of Lef1 also induced an
ectopic protrusion that contains ectopic transcripts for sox17, foxj1a, and
charon, and ectopic monocilia. Further genetic studies using this ectopic
expression platform revealed two distinct functions of Foxj1a; mediating Wnt
governed monocilia length elongation as well as charon transcription. The novel
Foxj1a-charon regulation is conserved in KV, and importantly, it is independent
of the canonical role of Foxj1a in the biosynthesis of motile cilia. Together
with the known function of motile cilia movement in generating asymmetric
expression of charon, our data put forward a hypothesis that Foxj1a confers both
ciliary and non-ciliary functions of Wnt signaling, which converge on charon to
regulate LR pattern formation.
PMID- 26432886
TI - Loss of arylformamidase with reduced thymidine kinase expression leads to
impaired glucose tolerance.
AB - Tryptophan metabolites have been linked in observational studies with type 2
diabetes, cognitive disorders, inflammation and immune system regulation. A rate
limiting enzyme in tryptophan conversion is arylformamidase (Afmid), and a double
knockout of this gene and thymidine kinase (Tk) has been reported to cause renal
failure and abnormal immune system regulation. In order to further investigate
possible links between abnormal tryptophan catabolism and diabetes and to examine
the effect of single Afmid knockout, we have carried out metabolic phenotyping of
an exon 2 Afmid gene knockout. These mice exhibit impaired glucose tolerance,
although their insulin sensitivity is unchanged in comparison to wild-type
animals. This phenotype results from a defect in glucose stimulated insulin
secretion and these mice show reduced islet mass with age. No evidence of a renal
phenotype was found, suggesting that this published phenotype resulted from loss
of Tk expression in the double knockout. However, despite specifically removing
only exon 2 of Afmid in our experiments we also observed some reduction of Tk
expression, possibly due to a regulatory element in this region. In summary, our
findings support a link between abnormal tryptophan metabolism and diabetes and
highlight beta cell function for further mechanistic analysis.
PMID- 26432887
TI - The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by
which the lack of Polycystin-2 leads to stimulation of CFTR.
AB - In autosomal dominant polycystic kidney disease (ADPKD), cyst inflation and
continuous enlargement are associated with marked transepithelial ion and fluid
secretion into the cyst lumen via cystic fibrosis transmembrane conductance
regulator (CFTR). Indeed, the inhibition or degradation of CFTR prevents the
fluid accumulation within cysts. The in vivo mechanisms by which the lack of
Polycystin-2 leads to CFTR stimulation are an outstanding challenge in ADPKD
research and may bring important biomarkers for the disease. However, hampering
their study, the available ADPKD in vitro cellular models lack the three
dimensional architecture of renal cysts and the ADPKD mouse models offer limited
access for live-imaging experiments in embryonic kidneys. Here, we tested the
zebrafish Kupffer's vesicle (KV) as an alternative model-organ. KV is a fluid
filled vesicular organ, lined by epithelial cells that express both CFTR and
Polycystin-2 endogenously, being each of them easily knocked-down. Our data on
the intracellular distribution of Polycystin-2 support its involvement in the KV
fluid-flow induced Ca(2+)-signalling. Mirroring kidney cysts, the KV lumen
inflation is dependent on CFTR activity and, as we clearly show, the knockdown of
Polycystin-2 results in larger KV lumens through overstimulation of CFTR. In
conclusion, we propose the zebrafish KV as a model organ to study the renal cyst
inflation. Favouring its use, KV volume can be easily determined by in vivo
imaging offering a live readout for screening compounds and genes that may
prevent cyst enlargement through CFTR inhibition.
PMID- 26432888
TI - Targeting of ribosomal protein S6 to dendritic spines by in vivo high frequency
stimulation to induce long-term potentiation in the dentate gyrus.
AB - Late phase long-term potentiation (L-LTP) in the hippocampus is believed to be
the cellular basis of long-term memory. Protein synthesis is required for
persistent forms of synaptic plasticity, including L-LTP. Neural activity is
thought to enhance local protein synthesis in dendrites, and one of the
mechanisms required to induce or maintain the long-lasting synaptic plasticity is
protein translation in the dendrites. One regulator of translational processes is
ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit.
Although polyribosomes containing rpS6 are observed in dendritic spines, it
remains unclear whether L-LTP induction triggers selective targeting of the
translational machinery to activated synapses in vivo. Therefore, we investigated
synaptic targeting of the translational machinery by observing rpS6
immunoreactivity during high frequency stimulation (HFS) for L-LTP induction in
vivo. Immunoelectron microscopic analysis revealed a selective but transient
increase in rpS6 immunoreactivity occurring as early as 15 min after the onset of
HFS in dendritic spine heads at synaptic sites receiving HFS. Concurrently,
levels of the rpS6 protein rapidly declined in somata of granule cells, as
determined using immunofluorescence microscopy. These results suggest that the
translational machinery is rapidly targeted to activated spines and that this
targeting mechanism may contribute to the establishment of L-LTP.
PMID- 26432889
TI - Genome-wide surveillance of mismatched alleles for graft-versus-host disease in
stem cell transplantation.
AB - Acute graft-versus-host disease (aGVHD) represents one of the major complications
in allogeneic stem cell transplantation and is primarily caused by genetic
disparity between the donor and recipient. In HLA-matched transplants, the
disparity is thought to be determined by loci encoding minor histocompatibility
antigens (minor H antigens), which are presented by specific HLA molecules. We
performed a genome-wide association study (GWAS) to identify minor H antigen loci
associated with aGVHD. A total of 500 568 single nucleotide polymorphisms (SNPs)
were genotyped for donors and recipients from 1589 unrelated bone marrow
transplants matched for HLA-A, -B, -C, -DRB1, and -DQB1, followed by the
imputation of unobserved SNPs. We interrogated SNPs whose disparity between the
donor and recipient was significantly associated with aGVHD development. Without
assuming HLA unrestriction, we successfully captured a known association between
HLA-DPB1 disparity (P = 4.50 * 10(-9)) and grade II-IV aGVHD development,
providing proof of concept for the GWAS design aimed at discovering genetic
disparity associated with aGVHD. In HLA-restricted analyses, whereby association
tests were confined to major subgroups sharing common HLA alleles to identify
putative minor H antigen loci, we identified 3 novel loci significantly
associated with grade III-IV aGVHD. Among these, rs17473423 (P = 1.20 * 10(-11))
at 12p12.1 within the KRAS locus showed the most significant association in the
subgroup, sharing HLA-DQB1*06:01. Our result suggested that a GWAS can be
successfully applied to identify allele mismatch associated with aGVHD
development, contributing to the understanding of the genetic basis of aGVHD.
PMID- 26432890
TI - Cutting Edge: Inhibiting TBK1 by Compound II Ameliorates Autoimmune Disease in
Mice.
AB - TANK-binding kinase 1 (TBK1) is a serine/threonine protein kinase that plays a
crucial role in innate immunity. Enhanced TBK1 function is associated with
autoimmune diseases and cancer, implicating the potential benefit of
therapeutically targeting TBK1. In this article, we examined a recently
identified TBK1 inhibitor Compound II on treating autoimmune diseases. We found
that Compound II is a potent and specific inhibitor of TBK1-mediated IFN
response. Compound II inhibited polyinosinic-polycytidylic acid-induced immune
activation in vitro and in vivo. Compound II treatment also ameliorated
autoimmune disease phenotypes of Trex1(-/-) mice, increased mouse survival, and
dampened the IFN gene signature in TREX1 mutant patient lymphoblasts. In
addition, we found that TBK1 gene expression is elevated in systemic lupus
erythematosus patient cells, and systemic lupus erythematosus cells with high IFN
signature responded well to Compound II treatment. Together, our findings
provided critical experimental evidence for inhibiting TBK1 with Compound II as
an effective treatment for TREX1-associated autoimmune diseases and potentially
other interferonopathies.
PMID- 26432891
TI - Identification of the SLAM Adapter Molecule EAT-2 as a Lupus-Susceptibility Gene
That Acts through Impaired Negative Regulation of Dendritic Cell Signaling.
AB - We showed previously that C57BL/6 congenic mice with an introgressed homozygous
70 cM (125.6 Mb) to 100 cM (179.8 Mb) interval on c1 from the lupus-prone New
Zealand Black (NZB) mouse develop high titers of antinuclear Abs and severe
glomerulonephritis. Using subcongenic mice, we found that a genetic locus in the
88-96 cM region was associated with altered dendritic cell (DC) function and
synergized with T cell functional defects to promote expansion of pathogenic
proinflammatory T cell subsets. In this article, we show that the promoter region
of the NZB gene encoding the SLAM signaling pathway adapter molecule EWS
activated transcript 2 (EAT-2) is polymorphic, which results in an ~ 70%
reduction in EAT-2 in DC. Silencing of the EAT-2 gene in DC that lacked this
polymorphism led to increased production of IL-12 and enhanced differentiation of
T cells to a Th1 phenotype in T cell-DC cocultures, reproducing the phenotype
observed for DC from congenic mice with the NZB c1 70-100 cM interval. SLAM
signaling was shown to inhibit production of IL-12 by CD40L-activated DCs.
Consistent with a role for EAT-2 in this inhibition, knockdown of EAT-2 resulted
in increased production of IL-12 by CD40-stimulated DC. Assessment of downstream
signaling following CD40 cross-linking in the presence or absence of SLAM cross
linking revealed that SLAM coengagement blocked activation of p38 MAPK and JNK
signaling pathways in DC, which was reversed in DC with the NZB EAT-2 allele. We
conclude that EAT-2 negatively regulates cytokine production in DC downstream of
SLAM engagement and that a genetic polymorphism that disturbs this process
promotes the development of lupus.
PMID- 26432892
TI - Regulatory B Cells with a Partial Defect in CD40 Signaling and Overexpressing
Granzyme B Transfer Allograft Tolerance in Rodents.
AB - Emerging knowledge regarding B cells in organ transplantation has demonstrated
that these cells can no longer be taken as mere generators of deleterious Abs but
can also act as beneficial players. We previously demonstrated in a rat model of
cardiac allograft tolerance induced by short-term immunosuppression an
accumulation in the blood of B cells overexpressing inhibitory molecules, a
phenotype also observed in the blood of patients that spontaneously develop graft
tolerance. In this study, we demonstrated the presence in the spleen of
regulatory B cells enriched in the CD24(int)CD38(+)CD27(+)IgD(-)IgM(+/low)
subpopulation, which are able to transfer donor-specific tolerance via IL-10 and
TGF-beta1-dependent mechanisms and to suppress in vitro TNF-alpha secretion.
Following anti-CD40 stimulation, IgD(-)IgM(+/low) B cells were blocked in their
plasma cell differentiation pathway, maintained high expression of the inhibitory
molecules CD23 and Bank1, and upregulated Granzyme B and Irf4, two molecules
described as highly expressed by regulatory B cells. Interestingly, these B cells
recognized specifically a dominant donor Ag, suggesting restricted specificity
that could lead to a particular B cell response. Regulatory B cells were not
required for induction of tolerance and appeared following Foxp3(+)CD4(+)CD25(+)
regulatory T cells, suggesting cooperation with regulatory T cells for their
expansion. Nevertheless, following transfer to new recipients, these B cells
migrated to the allograft, kept their regulatory profile, and promoted local
accumulation of Foxp3(+)CD4(+)CD25(+) regulatory T cells. Mechanisms of
regulatory B cells and their cell therapy potential are important to decipher in
experimental models to pave the way for future developments in the clinic.
PMID- 26432893
TI - Novel Role of TRPML2 in the Regulation of the Innate Immune Response.
AB - TRPMLs (or mucolipins) constitute a family of endosomal cation channels with
homology to the transient receptor potential superfamily. In mammals, the TRPML
family includes three members: TRPML1-3. Although TRPML1 and TRPML3 have been
well characterized, the cellular function of TRPML2 has remained elusive. To
address TRPML2 function in a physiologically relevant cell type, we first
analyzed TRPML2 expression in different mouse tissues and organs and found that
it was predominantly expressed in lymphoid organs and kidney. Quantitative RT-PCR
revealed tight regulation of TRPML2 at the transcriptional level. Although TRPML2
expression was negligible in resting macrophages, TRPML2 mRNA and protein levels
dramatically increased in response to TLR activation both in vitro and in vivo.
Conversely, TRPML1 and TRPML3 levels did not change upon TLR activation.
Immunofluorescence analysis demonstrated that endogenous TRPML2 primarily
localized to recycling endosomes both in culture and primary cells, in contrast
with TRPML1 and TRPML3, which distribute to the late and early endosomal pathway,
respectively. To better understand the in vivo function of TRPML2, we generated a
TRPML2-knockout mouse. We found that the production of several chemokines, in
particular CCL2, was severely reduced in TRPML2-knockout mice. Furthermore,
TRPML2-knockout mice displayed impaired recruitment of peripheral macrophages in
response to i.p. injections of LPS or live bacteria, suggesting a potential
defect in the immune response. Overall, our study reveals interesting differences
in the regulation and distribution of the members of the TRPML family and
identifies a novel role for TRPML2 in the innate immune response.
PMID- 26432894
TI - Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect
from Acute Colitis.
AB - In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial
cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure,
but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the
Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is
associated with an altered composition of the gut microbiota and exacerbates
inflammatory bowel disease. Colitic Tyk2(-/-) mice have less p-STAT3 in colon
tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs
show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22
STAT3 target genes is reduced in IECs from healthy and colitic Tyk2(-/-) mice.
Experiments with conditional Tyk2(-/-) mice reveal that IEC-specific depletion of
Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high
doses of rIL-22-Fc, indicating that Tyk2 deficiency can be rescued via the IL-22
receptor complex. The pivotal function of Tyk2 in IL-22-dependent colitis was
confirmed in Citrobacter rodentium-induced disease. Thus, Tyk2 protects against
acute colitis in part by amplifying inflammation-induced epithelial IL-22
signaling to STAT3.
PMID- 26432897
TI - Comment on "A Novel Thymoma-Associated Immunodeficiency with Increased Naive T
Cells and Reduced CD247 Expression".
PMID- 26432896
TI - Preferential Destruction of Interstitial Macrophages over Alveolar Macrophages as
a Cause of Pulmonary Disease in Simian Immunodeficiency Virus-Infected Rhesus
Macaques.
AB - To our knowledge, this study demonstrates for the first time that the AIDS virus
differentially impacts two distinct subsets of lung macrophages. The predominant
macrophages harvested by bronchoalveolar lavage (BAL), alveolar macrophages
(AMs), are routinely used in studies on human lung macrophages, are long-lived
cells, and exhibit low turnover. Interstitial macrophages (IMs) inhabit the lung
tissue, are not recovered with BAL, are shorter-lived, and exhibit higher
baseline turnover rates distinct from AMs. We examined the effects of SIV
infection on AMs in BAL fluid and IMs in lung tissue of rhesus macaques. SIV
infection produced massive cell death of IMs that contributed to lung tissue
damage. Conversely, SIV infection induced minimal cell death of AMs, and these
cells maintained the lower turnover rate throughout the duration of infection.
This indicates that SIV produces lung tissue damage through destruction of IMs,
whereas the longer-lived AMs may serve as a virus reservoir to facilitate HIV
persistence.
PMID- 26432898
TI - Response to Comment on "A Novel Thymoma-Associated Immunodeficiency with
Increased Naive T Cells and Reduced CD247 Expression".
PMID- 26432895
TI - Targeting Anti-Insulin B Cell Receptors Improves Receptor Editing in Type 1
Diabetes-Prone Mice.
AB - Autoreactive B lymphocytes that commonly arise in the developing repertoire can
be salvaged by receptor editing, a central tolerance mechanism that alters BCR
specificity through continued L chain rearrangement. It is unknown whether
autoantigens with weak cross-linking potential, such as insulin, elicit receptor
editing, or whether this process is dysregulated in related autoimmunity. To
resolve these issues, we developed an editing-competent model in which anti
insulin Vkappa125 was targeted to the Igkappa locus and paired with anti-insulin
VH125Tg. Physiologic, circulating insulin increased RAG-2 expression and was
associated with BCR replacement that eliminated autoantigen recognition in a
proportion of developing anti-insulin B lymphocytes. The proportion of anti
insulin B cells that underwent receptor editing was reduced in the type 1
diabetes-prone NOD strain relative to a nonautoimmune strain. Resistance to
editing was associated with increased surface IgM expression on immature (but not
transitional or mature) anti-insulin B cells in the NOD strain. The actions of
mAb123 on central tolerance were also investigated, because selective targeting
of insulin-occupied BCR by mAb123 eliminates anti-insulin B lymphocytes and
prevents type 1 diabetes. Autoantigen targeting by mAb123 increased RAG-2
expression and dramatically enhanced BCR replacement in newly developed B
lymphocytes. Administering F(ab')2123 induced IgM downregulation and reduced the
frequency of anti-insulin B lymphocytes within the polyclonal repertoire of
VH125Tg/NOD mice, suggesting enhanced central tolerance by direct BCR
interaction. These findings indicate that weak or faulty checkpoints for central
tolerance can be overcome by autoantigen-specific immunomodulatory therapy.
PMID- 26432899
TI - Nucleic Acid-Sensing Receptors: Rheostats of Autoimmunity and Autoinflammation.
AB - Distinct families of germline-encoded pattern recognition receptors can sense
both microbial and endogenous nucleic acids. These DNA and RNA sensors include
endosomal TLRs and cytosolic sensors upstream of stimulator of type I IFN genes
(STING) and MAVS. The existence of overlapping specificities for both foreign and
self nucleic acids suggests that, under optimal conditions, the activity of these
receptors is finely tuned to effectively mediate host defense yet constrain
pathogenic self-reactivity. This equilibrium becomes disrupted with the loss of
either TLR9 or STING. To maintain immune protection, this loss can be
counterbalanced by the elevated response of an alternative receptor(s).
Unfortunately, this adjustment can lead to an increased risk for the development
of systemic autoimmunity, as evidenced by the exacerbated clinical disease
manifestations of TLR9-deficient and STING-deficient autoimmune-prone mice. These
studies underscore the delicate balance normally maintained by tonic signals that
prevent unchecked immune responses to nucleic acids released during infections
and cellular duress or death.
PMID- 26432900
TI - Cytokine overproduction and crosslinker hypersensitivity are unlinked in Fanconi
anemia macrophages.
AB - The Fanconi anemia proteins participate in a canonical pathway that repairs cross
linking agent-induced DNA damage. Cells with inactivated Fanconi anemia genes are
universally hypersensitive to such agents. Fanconi anemia-deficient hematopoietic
stem cells are also hypersensitive to inflammatory cytokines, and, as
importantly, Fanconi anemia macrophages overproduce such cytokines in response to
TLR4 and TLR7/8 agonists. We questioned whether TLR-induced DNA damage is the
primary cause of aberrantly regulated cytokine production in Fanconi anemia
macrophages by quantifying TLR agonist-induced TNF-alpha production, DNA strand
breaks, crosslinker-induced chromosomal breakage, and Fanconi anemia core complex
function in Fanconi anemia complementation group C-deficient human and murine
macrophages. Although both M1 and M2 polarized Fanconi anemia cells were
predictably hypersensitive to mitomycin C, only M1 macrophages overproduced TNF
alpha in response to TLR-activating signals. DNA damaging agents alone did not
induce TNF-alpha production in the absence of TLR agonists in wild-type or
Fanconi anemia macrophages, and mitomycin C did not enhance TLR responses in
either normal or Fanconi anemia cells. TLR4 and TLR7/8 activation induced
cytokine overproduction in Fanconi anemia macrophages. Also, although TLR4
activation was associated with induced double strand breaks, TLR7/8 activation
was not. That DNA strand breaks and chromosome breaks are neither necessary nor
sufficient to account for the overproduction of inflammatory cytokines by Fanconi
anemia cells suggests that noncanonical anti-inflammatory functions of Fanconi
anemia complementation group C contribute to the aberrant macrophage phenotype
and suggests that suppression of macrophage/TLR hyperreactivity might prevent
cytokine-induced stem cell attrition in Fanconi anemia.
PMID- 26432901
TI - At the Bench: Neutrophil extracellular traps (NETs) highlight novel aspects of
innate immune system involvement in autoimmune diseases.
AB - The putative role of neutrophils in host defense against pathogens is a well
recognized aspect of neutrophil function. The discovery of neutrophil
extracellular traps has expanded the known range of neutrophil defense mechanisms
and catalyzed a discipline of research focused upon ways in which neutrophils can
shape the immunologic landscape of certain autoimmune diseases, including
systemic lupus erythematosus. Enhanced neutrophil extracellular trap formation
and impaired neutrophil extracellular trap clearance may contribute to
immunogenicity in systemic lupus erythematosus and other autoimmune diseases by
promoting the externalization of modified autoantigens, inducing synthesis of
type I IFNs, stimulating the inflammasome, and activating both the classic and
alternative pathways of the complement system. Vasculopathy is a central feature
of many autoimmune diseases, and neutrophil extracellular traps may contribute
directly to endothelial cell dysfunction, atherosclerotic plaque burden, and
thrombosis. The elucidation of the subcellular events of neutrophil extracellular
trap formation may generate novel, therapeutic strategies that target the innate
immune system in autoimmune and vascular diseases.
PMID- 26432902
TI - The Choice of Hemodialysis Membrane Affects Bisphenol A Levels in Blood.
AB - Bisphenol A (BPA), a component of some dialysis membranes, accumulates in CKD.
Observational studies have linked BPA exposure to kidney and cardiovascular
injury in humans, and animal studies have described a causative link. Normal
kidneys rapidly excrete BPA, but insufficient excretion may sensitize patients
with CKD to adverse the effects of BPA. Using a crossover design, we studied the
effect of dialysis with BPA-containing polysulfone or BPA-free polynephron
dialyzers on BPA levels in 69 prevalent patients on hemodialysis: 28 patients
started on polysulfone dialyzers and were switched to polynephron dialyzers; 41
patients started on polynephron dialyzers and were switched to polysulfone
dialyzers. Results were grouped for analysis. Mean BPA levels increased after one
hemodialysis session with polysulfone dialyzers but not with polynephron
dialyzers. Chronic (3-month) use of polysulfone dialyzers did not significantly
increase predialysis serum BPA levels, although a trend toward increase was
detected (from 48.8+/-6.8 to 69.1+/-10.1 ng/ml). Chronic use of polynephron
dialyzers reduced predialysis serum BPA (from 70.6+/-8.4 to 47.1+/-7.5 ng/ml,
P<0.05). Intracellular BPA in PBMCs increased after chronic hemodialysis with
polysulfone dialyzers (from 0.039+/-0.002 to 0.043+/-0.001 ng/10(6) cells,
P<0.01), but decreased with polynephron dialyzers (from 0.045+/-0.001 to 0.036+/
0.001 ng/10(6) cells, P<0.01). Furthermore, chronic hemodialysis with polysulfone
dialyzers increased oxidative stress in PBMCs and inflammatory marker
concentrations in circulation. In vitro, polysulfone membranes released
significantly more BPA into the culture medium and induced more cytokine
production in cultured PBMCs than did polynephron membranes. In conclusion,
dialyzer BPA content may contribute to BPA burden in patients on hemodialysis.
PMID- 26432903
TI - Complement Factor H-Related 5-Hybrid Proteins Anchor Properdin and Activate
Complement at Self-Surfaces.
AB - C3 glomerulopathy (C3G) is a severe kidney disease for which no specific therapy
exists. The causes of C3G are heterogeneous, and defective complement regulation
is often linked to C3G pathogenesis. Copy number variations in the complement
factor H-related (CFHR) gene cluster on chromosome 1q32 and CFHR5 mutant proteins
associate with this disease. Here, we identified CFHR5 as a pattern recognition
protein that binds to damaged human endothelial cell surfaces and to properdin,
the human complement activator. We found the two N-terminal short consensus
repeat domains of CFHR5 contact properdin and mediate dimer formation. These
properdin-binding segments are duplicated in two mutant CFHR5 proteins, CFHR2
CFHR5Hyb from German patients with C3G and CFHR5Dup from Cypriot patients with
C3G. Each of these mutated proteins assembled into large multimeric complexes
and, compared to CFHR5, bound damaged human cell surfaces and properdin with
greater intensity and exacerbated local complement activation. This enhanced
surface binding and properdin recruitment was further evidenced in the mesangia
of a transplanted and explanted kidney from a German patient with a CFHR2
CFHR5Hyb protein. Enhanced properdin staining correlated with local complement
activation with C3b and C5b-9 deposition on the mesangial cell surface in vitro
This gain of function in complement activation for two disease-associated CFHR5
mutants describes a new disease mechanism of C3G, which is relevant for defining
appropriate treatment options for this disorder.
PMID- 26432904
TI - Renal Deletion of 12 kDa FK506-Binding Protein Attenuates Tacrolimus-Induced
Hypertension.
AB - Tacrolimus is a widely used immunosuppressive drug that inhibits the phosphatase
calcineurin when bound to the 12 kDa FK506-binding protein (FKBP12). When this
binding occurs in T cells, it leads to immunosuppression. Tacrolimus also causes
side effects, however, such as hypertension and hyperkalemia. Previously, we
reported that tacrolimus stimulates the renal thiazide-sensitive sodium chloride
cotransporter (NCC), which is necessary for the development of hypertension.
However, it was unclear if tacrolimus-induced hypertension resulted from
tacrolimus effects in renal epithelial cells directly or in extrarenal tissues,
and whether inhibition of calcineurin was required. To address these questions,
we developed a mouse model in which FKBP12 could be deleted along the nephron.
FKBP12 disruption alone did not cause phenotypic effects. When treated with
tacrolimus, however, BP and the renal abundance of phosphorylated NCC were lower
in mice lacking FKBP12 along the nephron than in control mice. Mice lacking
FKBP12 along the nephron also maintained a normal relationship between plasma
potassium levels and the abundance of phosphorylated NCC with tacrolimus
treatment. In cultured cells, tacrolimus inhibited dephosphorylation of NCC.
Together, these results suggest that tacrolimus causes hypertension predominantly
by inhibiting calcineurin directly in cells expressing NCC, indicating thiazide
diuretics may be particularly effective for lowering BP in tacrolimus-treated
patients with hypertension.
PMID- 26432906
TI - Cracking the Egg: Potential of the Developing Chicken as a Model System for
Nonclinical Safety Studies of Pharmaceuticals.
AB - The advance of perinatal medicine has improved the survival of extremely
premature babies, thereby creating a new and heterogeneous patient group with
limited information on appropriate treatment regimens. The developing fetus and
neonate have traditionally been ignored populations with regard to safety studies
of drugs, making medication during pregnancy and in newborns a significant safety
concern. Recent initiatives of the Food and Drug Administration and European
Medicines Agency have been passed with the objective of expanding the safe
pharmacological treatment options in these patients. There is a consensus that
neonates should be included in clinical trials. Prior to these trials, drug leads
are tested in toxicity and pharmacology studies, as governed by several
guidelines summarized in the multidisciplinary International Conference on
Harmonization of Technical Requirements for Registration of Pharmaceuticals for
Human Use M3 (R2). Pharmacology studies must be performed in the major organ
systems: cardiovascular, respiratory, and central nervous system. The chicken
embryo and fetus have features that make the chicken a convenient animal model
for nonclinical safety studies in which effects on all of these organ systems can
be tested. The developing chicken is inexpensive, accessible, and nutritionally
self-sufficient with a short incubation time and is ideal for drug-screening
purposes. Other high-throughput models have been implemented. However, many of
these have limitations, including difficulty in mimicking natural tissue
architecture and function (human stem cells) and obvious differences from mammals
regarding the respiratory organ system and certain aspects of central nervous
system development (Caenorhabditis elegans, zebrafish).This minireview outlines
the potential and limitations of the developing chicken as an additional model
for the early exploratory phase of development of new pharmaceuticals.
PMID- 26432907
TI - Cancer vaccines in the new era of cancer immunotherapy.
PMID- 26432908
TI - Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine
selection pressure in a mixed infection model.
AB - Whooping cough or pertussis is a highly infectious respiratory disease in humans
caused by Bordetella pertussis. The use of acellular vaccines (ACV) has been
associated with the recent resurgence of pertussis in developed countries
including Australia despite high vaccination coverage where B. pertussis strains
that do not express pertactin (Prn), a key antigenic component of the ACV, have
emerged and become prevalent. In this study, we used an in vivo competition assay
in mice immunised with ACV and in naive (control) mice to compare the proportion
of colonisation with recent clinical Prn positive and Prn negative B. pertussis
strains from Australia. The Prn negative strain colonised the respiratory tract
more effectively than the Prn positive strain in immunised mice, out-competing
the Prn positive strain by day 3 of infection. However, in control mice, the Prn
positive strain out-competed the Prn negative strain. Our findings of greater
ability of Prn negative strains to colonise ACV-immunised mice are consistent
with reports of selective advantage for these strains in ACV-immunised humans.
PMID- 26432905
TI - Endocrine and other physiologic modulators of perinatal cardiomyocyte endowment.
AB - Immature contractile cardiomyocytes proliferate to rapidly increase cell number,
establishing cardiomyocyte endowment in the perinatal period. Developmental
changes in cellular maturation, size and attrition further contribute to cardiac
anatomy. These physiological processes occur concomitant with a changing hormonal
environment as the fetus prepares itself for the transition to extrauterine life.
There are complex interactions between endocrine, hemodynamic and nutritional
regulators of cardiac development. Birth has been long assumed to be the trigger
for major differences between the fetal and postnatal cardiomyocyte growth
patterns, but investigations in normally growing sheep and rodents suggest this
may not be entirely true; in sheep, these differences are initiated before birth,
while in rodents they occur after birth. The aim of this review is to draw
together our understanding of the temporal regulation of these signals and
cardiomyocyte responses relative to birth. Further, we consider how these
dynamics are altered in stressed and suboptimal intrauterine environments.
PMID- 26432909
TI - Genetic stability of live attenuated vaccines against potentially pandemic
influenza viruses.
AB - BACKGROUND: Ensuring genetic stability is a prerequisite for live attenuated
influenza vaccine (LAIV). This study describes the results of virus shedding and
clinical isolates' testing of Phase I clinical trials of Russian LAIVs against
potentially pandemic influenza viruses in healthy adults. METHODS: Three live
attenuated vaccines against potentially pandemic influenza viruses, H2N2 LAIV,
H5N2 LAIV and H7N3 LAIV, generated by classical reassortment in eggs, were
studied. For each vaccine tested, subjects were randomly distributed into two
groups to receive two doses of either LAIV or placebo at a 3:1 vaccine/placebo
ratio. Nasal swabs were examined for vaccine virus shedding by culturing in eggs
and by PCR. Vaccine isolates were tested for temperature sensitivity and cold
adaptation (ts/ca phenotypes) and for nucleotide sequence. RESULTS: The majority
of nasal wash positive specimens were detected on the first day following
vaccination. PCR method demonstrated higher sensitivity than routine virus
isolation in eggs. None of the placebo recipients had detectable vaccine virus
replication. All viruses isolated from the immunized subjects retained the ts/ca
phenotypic characteristics of the master donor virus (MDV) and were shown to
preserve all attenuating mutations described for the MDV. These data suggest high
level of vaccine virus genetic stability after replication in humans. During
manufacture process, no additional mutations occurred in the genome of H2N2 LAIV.
In contrast, one amino acid change in the HA of H7N3 LAIV and two additional
mutations in the HA of H5N2 LAIV manufactured vaccine lot were detected, however,
they did not affect their ts/ca phenotypes. CONCLUSIONS: Our clinical trials
revealed phenotypic and genetic stability of the LAIV viruses recovered from the
immunized volunteers. In addition, no vaccine virus was detected in the placebo
groups indicating the lack of person-to-person transmission. LAIV TRIAL
REGISTRATION at ClinicalTrials.gov: H7N3-NCT01511419; H5N2-NCT01719783; H2N2
NCT01982331.
PMID- 26432910
TI - No evidence for priming response in Galleria mellonella larvae exposed to toxin
protein PirA2B2 from Photorhabdus luminescens TT01: An association with the
inhibition of the host cellular immunity.
AB - There is accumulating evidence that many invertebrates including insects can
acquire enhanced immune protection against subsequently pathogens infection
through immune priming. However, whether the toxin protein from pathogenic
bacteria can induce such priming response remains unclear. Here we cloned,
expressed and purified the toxin Photorhabdus insect-related proteins A2B2
(PirA2B2) from Photorhabdus luminescens TT01. We primed Galleria mellonella with
sublethal dose of PirA2B2 and then challenged the larvae with viable P.
luminescens TT01 at 48 h after priming. We found no evidence for immune priming
in G. mellonella larvae exposed to PirA2B2. Priming the larvae with PirA2B2 did
not improve their resistance in a subsequent challenge with P. luminescens TT01.
Whereas a robust priming response was observed when the larvae exposed to
lipopolysaccharide (LPS) extracted from P. luminescens TT01. Because the larvae
primed with LPS showed significant higher resistance against P. luminescens TT01
infection than those of the PBS and BSA controls. Furthermore, we investigated
the changes of the cellular immune parameters, such as hemocyte counts,
phagocytic activity and encapsulation ability of the hemocytes, after priming. We
found that the toxin PirA2B2 significantly decreased the cellular immunity of the
larvae, whereas the LPS significantly increased them. These results indicated
that the degree of priming response in G. mellonella correlated positively to the
levels of cellular immune parameters, and the underlying mechanism in regulating
the immune priming of invertebrates was not homologous to that of the
immunological memory of vertebrates.
PMID- 26432911
TI - Is immunotherapy an opportunity for effective treatment of drug addiction?
AB - Immunotherapy has a great potential of becoming a new therapeutic strategy in the
treatment of addiction to psychoactive drugs. It may be used to treat addiction
but also to prevent neurotoxic complications of drug overdose. In preclinical
studies two immunological methods have been tested; active immunization, which
relies on the administration of vaccines and passive immunization, which relies
on the administration of monoclonal antibodies. Until now researchers have
succeeded in developing vaccines and/or antibodies against addiction to heroin,
cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has
been confirmed in preclinical studies. At present, clinical studies are being
conducted for vaccines against nicotine and cocaine and also anti-methamphetamine
monoclonal antibody. These preclinical and clinical studies suggest that
immunotherapy may be useful in the treatment of addiction and drug overdose.
However, there are a few problems to be solved. One of them is controlling the
level of antibodies due to variability between subjects. But even obtaining a
suitable antibody titer does not guarantee the effectiveness of the vaccine.
Additionally, there is a risk of intentional or unintentional overdose. As
vaccines prevent passing of drugs through the blood/brain barrier and thereby
prevent their positive reinforcement, some addicted patients may erroneously seek
higher doses of psychoactive substances to get "high". Consequently, vaccination
should be targeted at persons who have a strong motivation to free themselves
from drug dependency. It seems that immunotherapy may be an opportunity for
effective treatment of drug addiction if directed to adequate candidates for
treatment. For other addicts, immunotherapy may be a very important element
supporting psycho- and pharmacotherapy.
PMID- 26432912
TI - Env-2dCD4 S60C complexes act as super immunogens and elicit potent, broadly
neutralizing antibodies against clinically relevant human immunodeficiency virus
type 1 (HIV-1).
AB - The ability to induce a broadly neutralizing antibody (bNAb) response following
vaccination is regarded as a crucial aspect in developing an effective vaccine
against human immunodeficiency virus type 1 (HIV-1). The bNAbs target the HIV-1
envelope glycoprotein (Env) which is exposed on the virus surface, thereby
preventing cell entry. To date, conventional vaccine approaches such as the use
of Env-based immunogens have been unsuccessful. We expressed, purified,
characterized and evaluated the immunogenicity of several unique HIV-1 subtype C
Env immunogens in small animals. Here we report that vaccine immunogens based on
Env liganded to a two domain CD4 variant, 2dCD4(S60C) are capable of consistently
eliciting potent, broadly neutralizing antibody responses in New Zealand white
rabbits against a panel of clinically relevant HIV-1 pseudoviruses. This was
irrespective of the Env protein subtype and context. Importantly, depletion of
the anti-CD4 antibodies appeared to abrogate the neutralization activity in the
rabbit sera. Taken together, this data suggests that the Env-2dCD4(S60C)
complexes described here are "super" immunogens, and potentially immunofocus
antibody responses to a unique epitope spanning the 2dCD4(60C). Recent data from
the two available anti-CD4 monoclonal antibodies, Ibalizumab and CD4-Ig (and
bispecific variants thereof) have highlighted that the use of these broad and
potent entry inhibitors could circumvent the need for a conventional vaccine
targeting HIV-1. Overall, the ability of the unique Env-2dCD4(S60C) complexes to
elicit potent bNAb responses has not been described previously, reinforcing that
further investigation for their utility in preventing and controlling HIV-1/SIV
infection is warranted.
PMID- 26432914
TI - Maternal Immunization: Current status and future prospects.
PMID- 26432913
TI - Long-term immunogenicity and safety of an investigational herpes zoster subunit
vaccine in older adults.
AB - BACKGROUND: An investigational subunit vaccine containing the varicella-zoster
virus (VZV) glycoprotein E (gE) and the AS01B adjuvant system is being evaluated
for the prevention of herpes zoster (HZ) in older adults. A phase II trial
evaluating different formulations of this vaccine (containing 25MUg, 50MUg, or
100MUg gE) was conducted in adults >=60 years of age and showed that all
formulations elicited robust cellular and humoral immune responses for up to 3
years after vaccination. In this follow-up study in subjects who received two
doses of the 50MUg gE/AS01B formulation (HZ/su), we assessed the persistence of
the immune responses for up to 6 years after vaccination. METHODS: This phase II,
open-label, multicenter, single-group trial conducted in the Czech Republic,
Germany, Sweden, and the Netherlands followed 129 subjects who had received two
doses (2 months apart) of HZ/su during the initial trial. Vaccine-induced immune
responses (frequencies of gE-specific CD4(+) T cells expressing >=2 activation
markers and serum anti-gE antibody concentrations) were evaluated at 48, 60, and
72 months after the first HZ/su dose. RESULTS: Six years after vaccination with
HZ/su, gE-specific cell-mediated immune responses and anti-gE antibody
concentrations had decreased by 20-25% from month 36, but remained higher than
the prevaccination values. At month 72, the gE-specific cell-mediated immune
response was 3.8 times higher than the prevaccination value (477.3 vs. 119.4
activated gE-specific CD4(+) T cells per 10(6) cells), and the anti-gE antibody
concentration was 7.3 times higher than the prevaccination value (8159.0 vs.
1121.3mIU/mL). No vaccine-related serious adverse events were reported between
months 36 and 72. CONCLUSIONS: gE-specific cellular and humoral immune responses
persisted for 6 years after two-dose vaccination with HZ/su in healthy older
adults. No safety concerns were identified.
PMID- 26432916
TI - Protective antibody responses against A(H1N1)pdm09 primed by infection and
recalled by intranasal vaccination.
AB - This study investigated the effects of preceding infection and administration of
whole inactivated virus (WIV) vaccine on immune responses against influenza virus
challenge. Preceding infection alone provided minimal reduction in virus titer
following viral challenge. Single administration of intranasal or subcutaneous
WIV vaccine alone failed to reduce virus titers and induce antibody responses.
Subcutaneous administration of A/Narita/1/09 (A/NRT)-WIV after A/NRT infection
provided complete protection against infection and yielded low nasal IgA and high
serum IgG antibody responses. Subcutaneous administration of A/NRT-WIV after
A/Puerto Rico/8/34 (A/PR8) infection provided no protection. Conversely,
intranasal administration of A/NRT-WIV after A/NRT infection provided complete
protection and high nasal IgA and serum IgG antibody responses. While, intranasal
administration of A/NRT-WIV after A/PR8 infection provided moderate reduction in
viral titer with moderate increases in nasal IgA antibodies. These results
indicate that intranasal vaccination is superior to subcutaneous vaccination in
inducing protective immune responses after preceding heterologous infection.
PMID- 26432917
TI - Human organotypic retinal cultures (HORCs) as a chronic experimental model for
investigation of retinal ganglion cell degeneration.
AB - There is a growing need for models of human diseases that utilise native, donated
human tissue in order to model disease processes and develop novel therapeutic
strategies. In this paper we assessed the suitability of adult human retinal
explants as a potential model of chronic retinal ganglion cell (RGC)
degeneration. Our results confirmed that RGC markers commonly used in rodent
studies (NeuN, betaIII Tubulin and Thy-1) were appropriate for labelling human
RGCs and followed the expected differential expression patterns across, as well
as throughout, the macular and para-macular regions of the retina. Furthermore,
we showed that neither donor age nor post-mortem time (within 24 h) significantly
affected the initial expression levels of RGC markers. In addition, the
feasibility of using human post mortem donor tissue as a long-term model of RGC
degeneration was determined with RGC protein being detectable up to 4 weeks in
culture with an associated decline in RGC mRNA and significant, progressive,
apoptotic labelling of NeuN(+) cells. Differences in RGC apoptosis might have
been influenced by medium compositions indicating that media constituents could
play a role in supporting axotomised RGCs. We propose that using ex vivo human
explants may prove to be a useful model for testing the effectiveness of
neuroprotective strategies.
PMID- 26432915
TI - Plant-derived H7 VLP vaccine elicits protective immune response against H7N9
influenza virus in mice and ferrets.
AB - In March 2013, the Chinese Centre for Disease Control and Prevention confirmed
the first reported case of human infection with an avian influenza A H7N9 virus.
Infection with this virus often caused severe pneumonia and acute respiratory
distress syndrome resulting in a case fatality rate >35%. The risk of pandemic
highlighted, once again, the need for a more rapid and scalable vaccine response
capability. Here, we describe the rapid (19 days) development of a plant-derived
VLP vaccine based on the hemagglutinin sequence of influenza H7N9
A/Hangzhou/1/2013. The immunogenicity of the H7 VLP vaccine was assessed in mice
and ferrets after one or two intramuscular dose(s) with and without adjuvant
(alum or GLA-SETM). In ferrets, we also measured H7-specific cell-mediated
immunity. The mice and ferrets were then challenged with H7N9 A/Anhui/1/2013
influenza virus. A single immunization with the adjuvanted vaccine elicited a
strong humoral response and protected mice against an otherwise lethal challenge.
Two doses of unadjuvanted vaccine significantly increased humoral response and
resulted in 100% protection with significant reduction of clinical signs leading
to nearly asymptomatic infections. In ferrets, a single immunization with the
alum-adjuvanted H7 VLP vaccine induced strong humoral and CMI responses with
antigen-specific activation of CD3(+) T cells. Compared to animals injected with
placebo, ferrets vaccinated with alum-adjuvanted vaccine displayed no weight loss
during the challenge. Moreover, the vaccination significantly reduced the viral
load in lungs and nasal washes 3 days after the infection. This candidate plant
made H7 vaccine therefore induced protective responses after either one
adjuvanted or two unadjuvanted doses. Studies are currently ongoing to better
characterize the immune response elicited by the plant-derived VLP vaccines.
Regardless, these data are very promising for the rapid production of an
immunogenic and protective vaccine against this potentially pandemic virus.
PMID- 26432918
TI - Illumination from light-emitting diodes (LEDs) disrupts pathological cytokines
expression and activates relevant signal pathways in primary human retinal
pigment epithelial cells.
AB - Age-related macular degeneration (AMD) is the leading cause of blindness in the
aged people. The latest systemic review of epidemiological investigations
revealed that excessive light exposure increases the risk of AMD. With the
drastically increasing use of high-energy light-emitting diodes (LEDs) light in
our domestic environment nowadays, it is supposed to pose a potential oxidative
threat to ocular health. Retinal pigment epithelium (RPE) is the major ocular
source of pathological cytokines, which regulate local inflammation and
angiogenesis. We hypothesized that high-energy LED light might disrupt the
pathological cytokine expression of retinal pigment epithelium (RPE),
contributing to the pathogenesis of AMD. Primary human RPE cells were isolated
from eyecups of normal eye donors and seeded into plate wells for growing to
confluence. Two widely used multichromatic white light-emitting diodes (LEDs)
with correlated color temperatures (CCTs) of 2954 and 7378 K were used in this
experiment. The confluent primary RPE cells were under white LEDs light exposure
until 24 h. VEGF-A, IL-6, IL-8 and MCP-1 proteins and mRNAs were measured using
an ELISA kit and RT-PCR, respectively. Activation of mitogen-activated protein
kinases (MAPKs), Akt, Janus kinase (JAK)2 and Nuclear factor (NF)-kappaB signal
pathways after LEDs illumination were evaluated by western blotting analysis. The
level of reactive oxygen species (ROS) using chloromethyl- 2',7'
dichlorodihydrofluorescein diacetate. Inhibitors of relevant signal pathways and
anti-oxidants were added to the primary RPE cells before LEDs illumination to
evaluate their biological functions. We found that 7378 K light, but not 2954 K
upregulated the VEGF-A, IL-6, IL-8 and downregulated MCP-1 proteins and mRNAs
levels in a time-dependent manner. In parallel, initial activation of MAPKs and
NF-kappaB signal pathways were also observed after 7378 K light exposure.
Mechanistically, antioxidants for eliminating reactive oxygen species (ROS) and
targeted inhibitors of MAPKs and NF-kappaB significantly blocked 7378 K light
induced changes of specific cytokines, respectively. Our findings suggest that
7378 K light, not 2954 K induced upregulation of VEGF-A, IL-6, IL-8 and
downregulation of MCP-1 via ROS accumulation, activating MAPKs and NF-kappaB
signal pathways.
PMID- 26432919
TI - Dysregulation of VEGF-induced proangiogenic Ca2+ oscillations in primary
myelofibrosis-derived endothelial colony-forming cells.
AB - Endothelial progenitor cells could be implicated in the aberrant neoangiogenesis
that occurs in bone marrow and spleen in patients with primary myelofibrosis
(PMF). However, antivascular endothelial growth factor (VEGF) monotherapy had
only a modest and transient effect in these individuals. Recently it was found
that VEGF-induced proangiogenic intracellular Ca(2+) oscillations could be
impaired in endothelial progenitor cells of subjects with malignancies.
Therefore, we employed Ca(2+) imaging, wavelet analysis, and functional assays to
assess whether and how VEGF-induced Ca(2+) oscillations are altered in PMF
derived endothelial progenitor cells. We focused on endothelial colony-forming
cells (ECFCs), which are the only endothelial progenitor cell subtype capable of
forming neovessels both in vivo and in vitro. VEGF triggers repetitive Ca(2+)
spikes in both normal ECFCs (N-ECFCs) and ECFCs obtained from PMF patients (PMF
ECFCs). However, the spiking response to VEGF is significantly weaker in PMF
ECFCs. VEGF-elicited Ca(2+) oscillations are patterned by the interaction between
inositol-1,4,5-trisphosphate-dependent Ca(2+) mobilization and store-operated
Ca(2+) entry. However, in most PMF-ECFCs, Ca(2+) oscillations are triggered by a
store-independent Ca(2+) entry pathway. We found that diacylglycerol gates
transient receptor potential canonical 1 channel to trigger VEGF-dependent Ca(2+)
spikes by recruiting the phospholipase C/inositol-1,4,5-trisphosphate signaling
pathway, reflected as a decrease in endoplasmic reticulum Ca(2+) content.
Finally, we found that, apart from being less robust and dysregulated as compared
with N-ECFCs, VEGF-induced Ca(2+) oscillations modestly stimulate PMF-ECFC growth
and in vitro angiogenesis. These results may explain the modest effect of anti
VEGF therapies in PMF.
PMID- 26432920
TI - Aerosol from a candidate modified risk tobacco product has reduced effects on
chemotaxis and transendothelial migration compared to combustion of conventional
cigarettes.
AB - Reduction of harmful constituents by heating rather than combusting tobacco is a
promising new approach to reduce harmful effects associated with cigarette
smoking. We investigated the effect from a new candidate modified risk tobacco
product, the tobacco heating system (THS) 2.2, on the migratory behavior of
monocytes in comparison with combustible 3R4F reference cigarettes. The monocytic
cell line (THP-1) and human coronary arterial endothelial cells (HCAECs) were
used to analyze chemotaxis and transendothelial migration (TEM). To assess the
influence of aerosol extract from THS2.2 and smoke extract from 3R4F on toxicity
and inflammation, flow cytometry and ELISA assays were performed. The results
show that treatment of THP-1 cells with extract from 3R4F or THS2.2 induced
concentration-dependent increases in cytotoxicity and inflammation. The
inhibitory effects of THS2.2 extract for chemotaxis and TEM were ~18 times less
effective compared to 3R4F extract. Furthermore, extract from 3R4F or THS2.2
induced concentration-dependent decreases in the integrity of HCAEC monolayer.
For all examined endpoints, the extract from 3R4F showed more than one order of
magnitude stronger effects than that from THS2.2 extract. These data indicate the
potential of a heat not burn tobacco product to reduce the risk for
cardiovascular disease compared to combustible cigarettes.
PMID- 26432922
TI - CD4(+) T cell surface alpha enolase is lower in older adults.
AB - To identify novel cell ageing markers in order to gain insight into ageing
mechanisms, we adopted membrane enrichment and comparison of the CD4(+) T cell
membrane proteome (purified by cell surface labelling using Sulfo-NHS-SS-Biotin
reagent) between healthy young (n=9, 20-25 years) and older (n=10; 50-70 years)
male adults. Following two-dimensional gel electrophoresis (2DE) to separate
pooled membrane proteins in triplicates, the identity of protein spots with age
dependent differences (p<0.05 and >1.4 fold difference) was determined using
liquid chromatography-mass spectrometry (LC-MS/MS). Seventeen protein spot
density differences (ten increased and seven decreased in the older adult group)
were observed between young and older adults. From spot intensity analysis,
CD4(+) T cell surface alpha-enolase was decreased in expression by 1.5 fold in
the older age group; this was verified by flow cytometry (n=22) and qPCR with
significantly lower expression of cellular alpha-enolase mRNA and protein
compared to young adult CD4(+) T cells (p<0.05). In an independent age-matched
case-control study, lower CD4(+) T cell surface alpha-enolase expression was
observed in age-matched patients with cardiovascular disease (p<0.05). An immune
modulatory role has been proposed for surface alpha-enolase and our findings of
decreased expression suggest that deficits in surface alpha-enolase merit
investigation in the context of immune dysfunction during ageing and vascular
disease.
PMID- 26432924
TI - Therapeutics targeting innate immune/inflammatory responses through the
interleukin-6/JAK/STAT signal transduction pathway in patients with cancer.
AB - Over the last 15 years, there has been an evolution in the thinking of how tumors
grow and disseminate: from the earlier work where it was considered that the
intrinsic characteristics of the tumor largely determined the process to more
recent work where local and systemic inflammatory responses play a key role in
disease progression and survival in patients with cancer. Although the
immune/inflammatory responses to cancer are complex, it is clear that targeting
the host immune/inflammatory responses (in particular, innate/humoral responses)
has considerable potential to improve outcomes in patients with a variety of
common solid tumors. There are a wide variety of agents from the nonselective
glucocorticoids to the selective Janus Activated Kinase/Signal Transducer and
Activator of Transcription (JAK/STAT) inhibitors that has considerable
therapeutic potential. They may be considered to act through a main signal
transduction mechanism, the interleukin-6/JAK/STAT pathway. This work heralds a
new era in which it will be important not only to treat the tumor but also to
treat the host, so called oncoimmunology.
PMID- 26432921
TI - Cytoplasmic mRNA turnover and ageing.
AB - Messenger RNA (mRNA) turnover that determines the lifetime of cytoplasmic mRNAs
is a means to control gene expression under both normal and stress conditions,
whereas its impact on ageing and age-related disorders has just become evident.
Gene expression control is achieved at the level of the mRNA clearance as well as
mRNA stability and accessibility to other molecules. All these processes are
regulated by cis-acting motifs and trans-acting factors that determine the rates
of translation and degradation of transcripts. Specific messenger RNA granules
that harbor the mRNA decay machinery or various factors, involved in
translational repression and transient storage of mRNAs, are also part of the
mRNA fate regulation. Their assembly and function can be modulated to promote
stress resistance to adverse conditions and over time affect the ageing process
and the lifespan of the organism. Here, we provide insights into the complex
relationships of ageing modulators and mRNA turnover mechanisms.
PMID- 26432925
TI - Simultaneous quantitation of hexacosanoyl lysophosphatidylcholine, amino acids,
acylcarnitines, and succinylacetone during FIA-ESI-MS/MS analysis of dried blood
spot extracts for newborn screening.
AB - OBJECTIVES: The goal of this study was to include the quantitation of
hexacosanoyl lysophosphatidylcholine, a biomarker for X-linked
adrenoleukodystrophy and other peroxisomal disorders, in the routine extraction
and analysis procedure used to quantitate amino acids, acylcarnitines, and
succinylacetone during newborn screening. Criteria for the method included use of
a single punch from a dried blood spot, one simple extraction of the punch, no
high-performance liquid chromatography, and utilizing tandem mass spectrometry to
quantitate the analytes. DESIGN AND METHODS: Dried blood spot punches were
extracted with a methanolic solution of stable-isotope labeled internal
standards, formic acid, and hydrazine, followed by flow injection analysis
electrospray ionization-tandem mass spectrometry. RESULTS: Quantitation of amino
acids, acylcarnitines, and hexacosanoyl lysophosphatidylcholine using this
combined method was similar to results obtained using two separate methods.
CONCLUSIONS: A single dried blood spot punch extracted by a rapid (45min), simple
procedure can be analyzed with high throughput (2min per sample) to quantitate
amino acids, acylcarnitines, succinylacetone, and hexacosanoyl
lysophosphatidylcholine.
PMID- 26432926
TI - Translating depression biomarkers for improved targeted therapies.
AB - Mood disorders are among the most common medical conditions and cause amongst the
greatest disease burden. Currently approved antidepressants target monoamine
pathways; these medicines take many weeks to relieve symptoms, and most patients
do not have sustained responses. This review will highlight recent advances in
translational science identifying dysfunctional biochemical processes and
neuronal circuits associated with mood disorders. We will also summarize
strategies for targeting these pathways and for enhancing synaptic plasticity to
develop most effective and rapidly acting antidepressant therapies.
PMID- 26432923
TI - Therapeutic benefits of young, but not old, adipose-derived mesenchymal stem
cells in a chronic mouse model of bleomycin-induced pulmonary fibrosis.
AB - The observation that pulmonary inflammatory lesions and bleomycin (BLM)-induced
pulmonary fibrosis spontaneously resolve in young mice, whereas remaining
irreversible in aged mice suggests that impairment of pulmonary regeneration and
repair is associated with aging. Because mesenchymal stem cells (MSCs) may
promote repair after injury, we postulated that differences in MSCs from aged
mice may underlie postinjury fibrosis in aging. The potential for young-donor
MSCs to inhibit BLM-induced pulmonary fibrosis in aged male mice (>22 months) has
not been studied. Adipose-derived MSCs (ASCs) from young (4 months) and old (22
months) male mice were infused 1 day after intratracheal BLM administration. At
21-day sacrifice, aged BLM mice demonstrated lung fibrosis by Ashcroft score,
collagen content, and alpha(v)-integrin messenger RNA (mRNA) expression. Lung
tissue from aged BLM mice receiving young ASCs exhibited decreased fibrosis,
matrix metalloproteinase (MMP)-2 activity, oxidative stress, and markers of
apoptosis vs BLM controls. Lung mRNA expression of tumor necrosis factor-alpha
was also decreased in aged BLM mice receiving young-donor ASCs vs BLM controls.
In contrast, old-donor ASC treatment in aged BLM mice did not reduce fibrosis and
related markers. On examination of the cells, young-donor ASCs had decreased mRNA
expression of MMP-2, insulin-like growth factor (IGF) receptor, and protein
kinase B (AKT) activation compared with old-donor ASCs. These results show that
the BLM-induced pulmonary fibrosis in aged mice could be blocked by young-donor
ASCs and that the mechanisms involve changes in collagen turnover and markers of
inflammation.
PMID- 26432927
TI - Retinal Pigment Epithelial Atrophy in Neovascular Age-Related Macular
Degeneration After Ranibizumab Treatment.
AB - PURPOSE: To investigate the risk factors for development and progression of
retinal pigment epithelial (RPE) atrophy during ranibizumab treatment for
neovascular age-related macular degeneration (AMD) in Japanese patients. DESIGN:
Retrospective interventional case series. METHODS: This study included 195 eyes
with treatment-naive subfoveal neovascular AMD. All patients were treated with an
as-needed regimen after 3 monthly ranibizumab treatments. Color fundus
photography, spectral-domain optical coherence tomography, and fundus
autofluorescence were evaluated for RPE atrophy diagnosis. Baseline
characteristics and ARMS2 A69S and CFH I62V polymorphisms were analyzed for their
association with development and progression of RPE atrophy. RESULTS: Ten of 195
eyes (5.1%) had RPE atrophy at baseline; 3 had typical AMD and 7 had polypoidal
choroidal vasculopathy (PCV). Among 185 eyes without preexisting RPE atrophy at
baseline, 7 (3.8%) developed RPE atrophy at 12 months and 10 (5.4%) during the
mean follow-up of 26.7 months. The incidence of newly developed RPE atrophy was
lower in PCV than in typical AMD (P = .036), while the progression of the RPE
atrophy area was faster in typical AMD than in PCV (0.57 +/- 0.35 and 0.31 +/-
0.13 mm/year, respectively; P = .018). The ARMS2 A69S and CFH I62V polymorphisms
were significantly associated with the baseline RPE atrophy (P = .014 and P =
.009, respectively). CONCLUSIONS: The RPE atrophy developed in 5.4% of eyes with
neovascular AMD during the 26.7 months of ranibizumab treatment. When compared
with white individuals, RPE atrophy developed less frequently in Japanese
patients, but the progression rate was similar. The subtype of AMD thus affects
the development of RPE atrophy.
PMID- 26432928
TI - Photodynamic Therapy for Choroidal Metastasis.
AB - PURPOSE: To evaluate the effectiveness of photodynamic therapy (PDT) in the
management of choroidal metastasis. DESIGN: Retrospective, interventional case
series. METHODS: Patients with choroidal metastasis treated with PDT at a single
institution were reviewed. PDT was applied with verteporfin at a dose of 6
mg/m(2) body surface area and a 689 nm diode laser for 83 seconds. Visual acuity,
tumor basal diameter, tumor thickness by ultrasonography, and enhanced depth
imaging optical coherence tomography (EDI-OCT), as well as associated features
including subretinal fluid, were recorded before PDT and during follow-up
examinations. RESULTS: Twenty-one tumors in 13 eyes of 10 patients were included.
Eight tumors were treated with a single session of PDT, 11 tumors received 2
sessions, 1 tumor received 3 sessions, and 1 tumor received 5 sessions. At the
end of a mean follow-up of 12 months (range, 3-42 months), 9 eyes (69%) had
stable or improved visual acuity, while 4 eyes (31%) had decreased visual acuity.
Mean logMAR change in visual acuity was -0.09 (range, -1.3 to 0.8). Seventeen of
21 tumors (81%) were flat at last follow-up. The mean decrease in ultrasound
measured thickness was 0.83 mm (range, 2.6 mm decrease to 1.4 mm increase), while
the decrease in EDI-OCT-measured thickness was 400 MUm (range, 1280 MUm decrease
to 280 MUm increase). Eighteen tumors (86%) had complete resolution of subretinal
fluid. There were no PDT-related complications. CONCLUSIONS: Photodynamic therapy
may be an effective therapeutic option for the management of choroidal metastasis
in selected cases.
PMID- 26432929
TI - Geo-Epidemiology of Age-Related Macular Degeneration: New Clues Into the
Pathogenesis.
AB - PURPOSE: To evaluate the demographic, geographic, and race-related variables that
account for geographic variability in prevalence rates of age-related macular
degeneration (AMD). DESIGN: Systematic review, meta-regression, and decision-tree
analysis. METHODS: A systematic literature review of PubMed, Medline, Web of
Science, and Embase databases identified population-based studies on the
prevalence of AMD published before May 2014. Only population-based studies that
took place in a spatially explicit geographic area that could be geolocalized,
and used retinal photographs and standardized grading classifications, were
included. Latitude and longitude data (geolocalization) and the mean annual
insolation for the area where survey took place were obtained. Age-standardized
prevalence rates across studies were estimated using the direct standardization
method. Correlations between the prevalence of AMD and longitude and latitude
were obtained by regression analysis. A hierarchical Bayesian meta-regression
approach was used to assess the association between the prevalence of AMD and
other relevant factors. We further investigated the interplay between location
and these factors on the prevalence of AMD using regression based on conditional
inference decision trees. RESULTS: We observed significant inverse correlations
between latitude or longitude, and crude or age-standardized prevalence rates, of
early and late AMD (P < .001). Metaregression analysis showed that insolation,
latitude, longitude, age, and race have a significant effect on the prevalence
rates of early and late AMD (P < .001). Decision-tree analysis identified that
the most important predictive variable was race for early AMD (P = .002) and
insolation for late AMD (P = .001). CONCLUSIONS: Geographic position and
insolation are key factors in the prevalence of AMD.
PMID- 26432930
TI - Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is
associated with increased cortical inhibition.
AB - Huperzine A (HupA) is a naturally occurring compound found in the firmoss
Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full
pharmacologic profile is incompletely described. Since previous works suggested a
capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic
potential in pentylenetetrazole (PTZ) rat epilepsy model and explored its
mechanism of action by spectral EEG analysis and by paired-pulse transcranial
magnetic stimulation (ppTMS), a measure of GABA-mediated intracortical
inhibition. We tested whether HupA suppresses seizures in the rat PTZ acute
seizure model, and quantified latency to first myoclonus and to generalized tonic
clonic seizure, and spike frequency on EEG. Additionally, we measured power in
the EEG gamma frequency band which is associated with GABAergic cortical
interneuron activation. Then, as a step toward further examining the HupA
antiepileptic mechanism of action, we tested long-interval intracortical
inhibition (LICI) using ppTMS coupled with electromyography to assess whether
HupA augments GABA-mediated paired-pulse inhibition of the motor evoked
potential. We also tested whether the HupA effect on paired-pulse inhibition was
central or peripheral by comparison of outcomes following administration of HupA
or the peripheral acetylcholinesterase inhibitor pyridostigmine. We also tested
whether the HupA effect was dependent on central muscarinic or GABAA receptors by
co-administration of HupA and atropine or PTZ, respectively. In tests of
antiepileptic potential, HupA suppressed seizures and epileptic spikes on EEG.
Spectral EEG analysis also revealed enhanced gamma frequency band power with HupA
treatment. By ppTMS we found that HupA increases intracortical inhibition and
blocks PTZ-induced cortical excitation. Atropine co-administration with HupA did
not alter HupA-induced intracortical inhibition suggesting independent of
muscarinic acetylcholine receptors mechanism in this model. Last, pyridostigmine
did not affect the ppTMS-measured cortical inhibition suggesting that HupA
induced effect is centrally-mediated. Our data support antiepileptic HupA
applications, and suggest that such activity may be via enhancement of GABAergic
intracortical inhibition.
PMID- 26432931
TI - Voxel-based Gaussian naive Bayes classification of ischemic stroke lesions in
individual T1-weighted MRI scans.
AB - BACKGROUND: Manual lesion delineation by an expert is the standard for lesion
identification in MRI scans, but it is time-consuming and can introduce
subjective bias. Alternative methods often require multi-modal MRI data, user
interaction, scans from a control population, and/or arbitrary statistical
thresholding. NEW METHOD: We present an approach for automatically identifying
stroke lesions in individual T1-weighted MRI scans using naive Bayes
classification. Probabilistic tissue segmentation and image algebra were used to
create feature maps encoding information about missing and abnormal tissue. Leave
one-case-out training and cross-validation was used to obtain out-of-sample
predictions for each of 30 cases with left hemisphere stroke lesions. RESULTS:
Our method correctly predicted lesion locations for 30/30 un-trained cases. Post
processing with smoothing (8mm FWHM) and cluster-extent thresholding (100 voxels)
was found to improve performance. COMPARISON WITH EXISTING METHOD: Quantitative
evaluations of post-processed out-of-sample predictions on 30 cases revealed high
spatial overlap (mean Dice similarity coefficient=0.66) and volume agreement
(mean percent volume difference=28.91; Pearson's r=0.97) with manual lesion
delineations. CONCLUSIONS: Our automated approach agrees with manual tracing. It
provides an alternative to automated methods that require multi-modal MRI data,
additional control scans, or user interaction to achieve optimal performance. Our
fully trained classifier has applications in neuroimaging and clinical contexts.
PMID- 26432932
TI - Use of von Frey filaments to assess nociceptive sensitization in the hornworm,
Manduca sexta.
AB - BACKGROUND: The hornworm Manduca sexta exhibits a defensive strike to noxious
assaults, a response that is robust and is easily observed by experimenters. Von
Frey filaments and methods typical for studying nociception in other animals were
used to assess the strike response in M. sexta. NEW METHODS: A series of von Frey
filaments was applied to the body wall in ascending order and the data generated
were used to determine the strike threshold by (i) the up-and-down method, (ii)
the first response method, and (iii) the simplified up-and-down order method
(SUDO). The effect of a noxious pinch on strike threshold was assessed.
COMPARISON WITH EXISTING METHODS: To our knowledge none of these methods has been
used on M. sexta previously, making the use of the up-and-down and SUDO methods
the first in an invertebrate. The use of the first response method has been used
in other invertebrates, and the method appears equally suited to M. sexta.
RESULTS: All three methods were successful in monitoring the threshold
sensitivity to touch, which was lowered (sensitized) by tissue damage induced
with a pinch. Sensitization lasted 19h. CONCLUSIONS: All three methods of
assessing nociception were successfully applied to quantify the defensive strike
response in M. sexta, although the SUDO method required empirical assessment of
which filament to start the test sequence with. The results revealed both short-
and long-term sensitization. These methods should prove to be useful for
quantifying sensitization in M. sexta.
PMID- 26432933
TI - Isolating dividing neural and brain tumour cells for gene expression profiling.
AB - BACKGROUND: The characterisation of dividing brain cells is fundamental for
studies ranging from developmental and stem cell biology, to brain cancers.
Whilst there is extensive anatomical data on these dividing cells, limited gene
transcription data is available due to technical constraints. NEW METHOD: We
focally isolated dividing cells whilst conserving RNA, from culture, primary
neural tissue and xenografted glioma tumours, using a thymidine analogue that
enables gene transcription analysis. RESULTS: 5-ethynyl-2-deoxyuridine labels the
replicating DNA of dividing cells. Once labelled, cultured cells and tissues were
dissociated, fluorescently tagged with a revised click chemistry technique and
the dividing cells isolated using fluorescence-assisted cell sorting. RNA was
extracted and analysed using real time PCR. Proliferation and maturation related
gene expression in neurogenic tissues was demonstrated in acutely and 3 day old
labelled cells, respectively. An elevated expression of marker and pathway genes
was demonstrated in the dividing cells of xenografted brain tumours, with the non
dividing cells showing relatively low levels of expression. COMPARISON WITH
EXISTING METHOD: BrdU "immune-labelling", the most frequently used protocol for
detecting cell proliferation, causes complete denaturation of RNA, precluding
gene transcription analysis. This EdU labelling technique, maintained cell
integrity during dissociation, minimized copper exposure during labelling and
used a cell isolation protocol that avoided cell lysis, thus conserving RNA.
CONCLUSIONS: The technique conserves RNA, enabling the definition of cell
proliferation-related changes in gene transcription of neural and pathological
brain cells in cells harvested immediately after division, or following a period
of maturation.
PMID- 26432934
TI - Growing neuronal islands on multi-electrode arrays using an accurate positioning
MUCP device.
AB - BACKGROUND: Multi-electrode arrays (MEAs) allow non-invasive multi-unit recording
in-vitro from cultured neuronal networks. For sufficient neuronal growth and
adhesion on such MEAs, substrate preparation is required. Plating of dissociated
neurons on a uniformly prepared MEA's surface results in the formation of
spatially extended random networks with substantial inter-sample variability.
Such cultures are not optimally suited to study the relationship between defined
structure and dynamics in neuronal networks. To overcome these shortcomings,
neurons can be cultured with pre-defined topology by spatially structured surface
modification. Spatially structuring a MEA surface accurately and reproducibly
with the equipment of a typical cell-culture laboratory is challenging. NEW
METHOD: In this paper, we present a novel approach utilizing micro-contact
printing (MUCP) combined with a custom-made device to accurately position
patterns on MEAs with high precision. We call this technique AP-MUCP (accurate
positioning micro-contact printing). COMPARISON WITH EXISTING METHODS: Other
approaches presented in the literature using MUCP for patterning either relied on
facilities or techniques not readily available in a standard cell culture
laboratory, or they did not specify means of precise pattern positioning.
CONCLUSION: Here we present a relatively simple device for reproducible and
precise patterning in a standard cell-culture laboratory setting. The patterned
neuronal islands on MEAs provide a basis for high throughput electrophysiology to
study the dynamics of single neurons and neuronal networks.
PMID- 26432935
TI - Reply by Authors.
PMID- 26432936
TI - Re: Tunneled Buccal Mucosa Tube Grafts for Repair of Proximal Hypospadias: R.
Fine, E. F. Reda, P. Zelkovic, J. Gitlin, J. Freyle, I. Franco and L. S. Palmer J
Urol, suppl., 2015;193:1813-1817.
PMID- 26432937
TI - Reply by Authors.
PMID- 26432938
TI - Re: Comparative Effectiveness of Targeted vs Empirical Antibiotic Prophylaxis to
Prevent Sepsis from Transrectal Prostate Biopsy: A Retrospective Analysis: M. A.
Liss, W. Kim, D. Moskowitz and R. J. Szabo J Urol 2015;194:397-402.
PMID- 26432940
TI - Spontaneous esophageal perforation (Boerhaave syndrome) successfully treated with
an over-the-scope clip and fully covered metal stent.
PMID- 26432939
TI - Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and
naloxone-precipitated withdrawal symptoms in morphine-dependent mice.
AB - Opioid abuse and dependence have evolved into an international epidemic as a
significant clinical and societal problem with devastating consequences. Repeated
exposure to the opioid, for example morphine, can induce profound, long-lasting
behavioral sensitization and physical dependence, which are thought to reflect
neuroplasticity in neural circuitry. Central serotonin (5-HT) neurotransmission
participates in the development of dependence on and the expression of withdrawal
from morphine. Serotonin 5-HT(2C) receptor (5-HT(2C)R) agonists suppress
psychostimulant nicotine or cocaine-induced behavioral sensitization and drug
seeking behavior; however, the impact of 5-HT(2C)R agonists on behaviors relevant
to opioid abuse and dependence has not been reported. In the present study, the
effects of 5-HT(2C)R activation on the behavioral sensitization and naloxone
precipitated withdrawal symptoms were examined in mice underwent repeated
exposure to morphine. Male mice received morphine (10 mg/kg, s.c.) to develop
behavioral sensitization. Lorcaserin, a 5-HT(2C)R agonist, prevented the
induction and expression, but not the development, of morphine-induced behavioral
sensitization. Another cohort of mice received increasing doses of morphine over
a 7-day period to induce morphine-dependence. Pretreatment of lorcaserin, or the
positive control clonidine (an alpha 2-adrenoceptor agonist), ameliorated the
naloxone-precipitated withdrawal symptoms. SB 242084, a selective 5-HT(2C)R
antagonist, prevented the lorcaserin-mediated suppression of behavioral
sensitization and withdrawal. Chronic morphine treatment was associated with an
increase in the expression of 5-HT(2C)R protein in the ventral tegmental area,
locus coeruleus and nucleus accumbens. These findings suggest that 5-HT(2C)R can
modulate behavioral sensitization and withdrawal in morphine-dependent mice, and
the activation of 5-HT(2C)R may represent a new avenue for the treatment of
opioid addiction.
PMID- 26432941
TI - The "Moonsault" maneuver: retroflexed ileocecal valve insertion.
PMID- 26432942
TI - Combined volume reduction with the loop-and-leave technique permits safe
endoscopic management of high-risk giant gastric polyps.
PMID- 26432943
TI - Type III choledochal cyst and anomalous pancreatobiliary junction.
PMID- 26432944
TI - Peroral endoscopic myotomy with simultaneous submucosal and muscle dissection for
achalasia with severe interlayer adhesions.
PMID- 26432945
TI - convISA: A simple, convoluted method for isotopomer spectral analysis of fatty
acids and cholesterol.
AB - Isotopomer spectral analysis (ISA) is a simple approach for modelling the
cellular synthesis of fatty acids and cholesterol in a stable isotope labelling
experiment. In the simplest model, fatty acid biosynthesis is described by two
key parameters: the fractional enrichment of acetyl-CoA from the labelled
substrate, D, and the fractional de novo synthesis of the fatty acid during the
exposure to the labelled substrate, g(t). The model can also be readily extended
to include synthesis via elongation of unlabelled shorter fatty acids. This
modelling strategy is less complex than metabolic flux analysis and only requires
the measurement of the mass isotopologues of a single metabolite. However,
software tools to perform these calculations are not freely available. We have
developed an algorithm (convISA), implemented in MATLAB(TM), which employs the
convolution (Cauchy product) of mass isotopologue distributions (MIDs) for ISA of
fatty acids and cholesterol. In our method, the MIDs of each molecule are
constructed as a single entity rather than deriving equations for individual
isotopologues. The flexibility of this method allows the model to be applied to
raw data as well as to data that has been corrected for natural isotope
abundance. To test the algorithm, convISA was applied to 238 MIDs of methyl
palmitate available from the literature, for which ISA parameters had been
calculated via other methods. A very high correlation was observed between
estimates of the D and g(t) parameters from convISA with both published values,
and estimates generated by our own metabolic flux analysis using a simplified
stoichiometric model (r=0.981 and 0.944, and 0.996 and 0.942). We also
demonstrate the application of the convolution ISA approach to cholesterol
biosynthesis; the model was applied to measurements made on MCF7 cells cultured
in U-(13)C-glucose. In conclusion, we believe that convISA offers a convenient,
flexible and transparent framework for metabolic modelling that will help
facilitate the application of ISA to future experiments.
PMID- 26432946
TI - Survival of rat cerebrocortical neurons after rickettsial infection.
AB - Neuroinvasive microorganisms are suspected to play an important role in the
etiopathogenesis of neurological diseases. However, direct evidence for the
pathogenic function is still missing. The main aim of this study was to
investigate biochemical and morphological changes that may occur as a result of
an in vitro infection of rat cerebrocortical neurons by selected members of the
genus Rickettsia. Our results showed that survival of the neurons is
significantly reduced after the infection. Intracellular level of ATP is
gradually decreased and inversely correlates with the load of rickettsiae.
Immunofluorescence revealed that rickettsiae can enter the neurons and are
localized in perinuclear space and also in neuronal processes. Data obtained in
this study correspond to the idea of possible involvement of rickettsiae in the
etiopathogenesis of various neuropathies.
PMID- 26432948
TI - First report of a NDM-producing Providencia rettgeri strain in the state of Sao
Paulo.
PMID- 26432947
TI - Infection and characterization of Toxoplasma gondii in human induced neurons from
patients with brain disorders and healthy controls.
AB - Toxoplasma gondii is a protozoan parasite capable of establishing persistent
infection within the brain. Serological studies in humans have linked exposure to
Toxoplasma to neuropsychiatric disorders. However, serological studies have not
elucidated the related molecular mechanisms within neuronal cells. To address
this question, we used human induced neuronal cells derived from peripheral
fibroblasts of healthy individuals and patients with genetically-defined brain
disorders (i.e. childhood-onset schizophrenia with disease-associated copy number
variations). Parasite infection was characterized by differential detection of
tachyzoites and tissue cysts in induced neuronal cells. This approach may aid
study of molecular mechanisms underlying individual predisposition to Toxoplasma
infection linked to neuropathology of brain disorders.
PMID- 26432950
TI - Establishment and validation of a 384-well antibacterial assay amenable for high
throughput screening and combination testing.
AB - A 384-well-based antibacterial assay amenable for high-throughput screening and
combination testing is described. The assay uses 100-500nL of test compounds and
tolerates up to 2.5% dimethyl sulfoxide concentrations. It can be used for
screening compound libraries and testing combinatory/synergistic/antagonistic
effects of antibiotics, small molecules, and natural product extracts.
PMID- 26432949
TI - Recombinant expression, purification and preliminary biophysical and structural
studies of C-terminal carbohydrate recognition domain from human galectin-4.
AB - Galectin-4 (Gal4), a tandem-repeat type galectin, is expressed in healthy
epithelium of the gastrointestinal tract. Altered levels of Gal4 expression are
associated with different types of cancer, suggesting its usage as a diagnostic
marker as well as target for drug development. The functional data available for
this class of proteins suggest that the wide spectrum of cellular activities
reported for Gal4 relies on distinct glycan specificity and structural
characteristics of its two carbohydrate recognition domains. In the present work,
two independent constructs for recombinant expression of the C-terminal domain of
human galectin-4 (hGal4-CRD2) were developed. His6-tagged and untagged
recombinant proteins were overexpressed in Escherichia coli, and purified by
affinity chromatography followed by gel filtration. Correct folding and activity
of hGal4-CRD2 were assessed by circular dichroism and fluorescence
spectroscopies, respectively. Diffraction quality crystals were obtained by vapor
diffusion sitting drop setup and the crystal structure of CRD2 was solved by
molecular replacement techniques at 1.78 A resolution. Our work describes the
development of important experimental tools that will allow further studies in
order to correlate structure and binding properties of hGal4-CRD2 and human
galectin-4 functional activities.
PMID- 26432951
TI - Exenatide exerts a PKA-dependent positive inotropic effect in human atrial
myocardium: GLP-1R mediated effects in human myocardium.
AB - Glucagon-like peptide-1 receptor (GLP-1R) agonists are a rapidly growing class of
drugs developed for treating type-2 diabetes mellitus. Patients with diabetes
carry an up to 5-fold greater mortality risk compared to non-diabetic patients,
mainly as a result of cardiovascular diseases. Although beneficial cardiovascular
effects have been reported, exact mechanisms of GLP-1R-agonist action in the
heart, especially in human myocardium, are poorly understood. The effects of GLP
1R-agonists (exenatide, GLP-1(7-36)NH2, PF-06446009, PF-06446667) on cardiac
contractility were tested in non-failing atrial and ventricular trabeculae from
72 patients. The GLP-1(7-36)NH2 metabolite, GLP-1(9-36)NH2, was also examined. In
electrically stimulated trabeculae, the effects of compounds on isometric force
were measured in the absence and presence of pharmacological inhibitors of signal
transduction pathways. The role of beta-arrestin signaling was examined using a
beta-arrestin partial agonist, PF-06446667. Expression levels were tested by
immunoblots. Translocation of GLP-1R downstream molecular targets, Epac2, GLUT-1
and GLUT-4, were assessed by fluorescence microscopy. All tested GLP-1R-agonists
significantly increased developed force in human atrial trabeculae, whereas GLP
1(9-36)NH2 had no effect. Exendin(9-39)NH2, a GLP-1R-antagonist, and H-89 blunted
the inotropic effect of exenatide. In addition, exenatide increased PKA-dependent
phosphorylation of phospholamban (PLB), GLUT-1 and Epac2 translocation, but not
GLUT-4 translocation. Exenatide failed to enhance contractility in ventricular
myocardium. Quantitative real-time PCR (qRT-PCR) revealed a significant higher
GLP-1R expression in the atrium compared to ventricle. Exenatide increased
contractility in a dose-dependent manner via GLP-1R/cAMP/PKA pathway and induced
GLUT-1 and Epac2 translocation in human atrial myocardium, but had no effect in
ventricular myocardium. Therapeutic use of GLP-1R-agonists may therefore impart
beneficial effects on myocardial function and remodelling.
PMID- 26432952
TI - Early-life adversity and brain development: Is the microbiome a missing piece of
the puzzle?
AB - The prenatal and postnatal early-life periods are both dynamic and vulnerable
windows for brain development. During these important neurodevelopmental phases,
essential processes and structures are established. Exposure to adverse events
that interfere with this critical sequence of events confers a high risk for the
subsequent emergence of mental illness later in life. It is increasingly accepted
that the gastrointestinal microbiota contributes substantially to shaping the
development of the central nervous system. Conversely, several studies have shown
that early-life events can also impact on this gut community. Due to the
bidirectional communication between the gut and the brain, it is possible that
aberrant situations affecting either organ in early life can impact on the other.
Studies have now shown that deviations from the gold standard trajectory of gut
microbiota establishment and development in early life can lead not only to
disorders of the gastrointestinal tract but also complex metabolic and immune
disorders. These are being extended to disorders of the central nervous system
and understanding how the gut microbiome shapes brain and behavior during early
life is an important new frontier in neuroscience.
PMID- 26432953
TI - Bilateral retinal microglial response to unilateral optic nerve transection in
rats.
AB - When retinal ganglion cells undergo apoptosis after optic nerve (ON) injury,
microglial cells proliferate and promptly clear the degenerated debris in the
ipsilateral retina. However, microglial changes in the contralateral retina have
not been fully elucidated. This study characterized the long-term bilateral
retinal microglial responses after unilateral ON transection. We analyzed the
time course of proliferation and morphology changes of microglial cells, between
3 days and 12 weeks post ON transection, of undisturbed and reactive microglia in
bilateral retinas of adult Fischer rats with unilateral ON transection. Microglia
in retinas without ON transection were distributed homogeneously and possessed a
highly ramified morphology, as judged by immunohistochemistry for ionized calcium
binding adapter molecule 1 (Iba1). After ON transection, microglia density in the
ipsilateral retina increased gradually from 3 days to 2 weeks, and decreased from
3 weeks to 12 weeks, along with dramatic inverted alteration of process branch
points of microglia in the ganglion cell layer (GCL). Transformation of ramified
microglia into ameboid-like macrophages with few branching processes was observed
in the ipsilateral retina from 1 week to 3 weeks. Though an increase in
microglial density was weak in the contralateral retina and could only be
statistically detected in the central retina, the morphological alteration over
time was obvious and similar to that of the ipsilateral retina. In the inner
plexiform layer (IPL), cell density and morphological changes of microglia in
both the ipsilateral and contralateral retina were not prominent. These findings
indicates that, though proliferation of microglial cells is weak in the
contralateral retina after unilateral ON transection, conspicuous alterations in
microglial morphology occur bilaterally. These suggest that using the
contralateral retina as a control in studies of retinal degeneration should be
considered with caution.
PMID- 26432954
TI - Animal models for diabetes: Understanding the pathogenesis and finding new
treatments.
AB - Diabetes mellitus is a lifelong, metabolic disease that is characterised by an
inability to maintain normal glucose homeostasis. There are several different
forms of diabetes, however the two most common are Type 1 and Type 2 diabetes.
Type 1 diabetes is caused by the autoimmune destruction of pancreatic beta cells
and a subsequent lack of insulin production, whilst Type 2 diabetes is due to a
combination of both insulin resistance and an inability of the beta cells to
compensate adequately with increased insulin release. Animal models are
increasingly being used to elucidate the mechanisms underlying both Type 1 and
Type 2 diabetes as well as to identify and refine novel treatments. However, a
wide range of different animal models are currently in use. The majority of these
models are suited to addressing certain specific aspects of diabetes research,
but may be of little use in other studies. All have pros and cons, and selecting
an appropriate model for addressing a specific question is not always a trivial
task and will influence the study results and their interpretation. Thus, as the
number of available animal models increases it is important to consider the
potential roles of these models in the many different aspects of diabetes
research. This review gathers information on the currently used experimental
animal models of both Type 1 and Type 2 diabetes and evaluates their advantages
and disadvantages for research purposes and details the factors that should be
taken into account in their use.
PMID- 26432955
TI - How important is local food to organic-minded consumers?
AB - The study deals with German consumers' attitudes towards organic food and local
food, their food purchase behaviour and their personal characteristics. The
purpose is to investigate the differences in attitudes and willingness-to-pay
values between consumers who consider the organic production of food (very)
important and those who consider it less important. This study combines a
consumer survey with an in-store, discrete choice experiment. In the analysis,
findings from the consumer survey were related to the choices made by consumers
in the experiment. Consumers' preferences and willingness-to-pay values were
estimated through random parameter logit modelling. Organic-minded consumers
(i.e. those who regarded organic food production as (very) important in the
survey) have stronger preferences and estimated willingness-to-pay values for
organic as well as local products. Locally produced food, as opposed to food from
neighbouring countries or non-EU countries, is preferred over organically
produced food by both consumer groups which demonstrates that organic-minded
consumers do not only consider organic food production as important, but also
value local food production in a purchase situation. Hence, it can be assumed
that local food production complements organic food production for the group of
organic-minded consumers. This contribution is the first study dealing with local
and organic food purchase behaviour in Germany that examines four different
products and is carried out in rural as well as urban locations in four different
regions. Due to the application of a choice experiment including no-choice
options and binding purchase decisions, the results are expected to be closer to
real purchase situations than results of direct questioning and choice
experiments in online applications.
PMID- 26432956
TI - Long-term smoking cessation and heart rate dynamics in an aging healthy cohort:
Is it possible to fully recover?
AB - AIM: To evaluate the long-term influence of smoking cessation on the regulation
of the autonomic cardiovascular system in an aging general population, using the
subpopulation of lifelong non-smokers as control group. METHODS: We analyzed 1481
participants aged >=50 years from the SAPALDIA cohort. In each participant, heart
rate variability and heart rate dynamics were characterized by means of various
quantitative analyzes of the inter-beat interval time series generated from 24
hour electrocardiogram recordings. Each parameter obtained was then used as the
outcome variable in multivariable linear regression models in order to evaluate
the association with smoking status and time elapsed since smoking cessation. The
models were adjusted for known confounding factors and stratified by the time
elapsed since smoking cessation. RESULTS: Our findings indicate that smoking
triggers adverse changes in the regulation of the cardiovascular system, even at
low levels of exposure since current light smokers exhibited significant changes
as compared to lifelong non-smokers. Moreover, there was evidence for a dose
response effect. Indeed, the changes observed in current heavy smokers were more
marked as compared to current light smokers. Furthermore, full recovery was
achieved in former smokers (i.e., normalization to the level of lifelong non
smokers). However, while light smokers fully recovered within the 15 first years
of cessation, heavy former smokers might need up to 15-25 years to fully recover.
CONCLUSION: This study supports the substantial benefits of smoking cessation,
but also warns of important long-term alterations caused by heavy smoking.
PMID- 26432957
TI - Heme oxygenase-1, a novel target for the treatment of diabetic complications:
focus on diabetic peripheral neuropathy.
AB - Diabetic neuropathy is a complex disorder induced by long standing diabetes. Many
signaling pathways and transcription factors have been proposed to be involved in
the development and progression of related processes. Years of research points to
critical role of oxidative stress, neuroinflammation and apoptosis in the
pathogenesis of neuropathy in diabetes. Heme oxygenase-1 (HO-1) is heat-shock
protein induced under conditions of different kinds of stress and has been
implicated in cellular defense against oxidative stress. HO-1 degrades heme to
biliverdin, carbon monoxide (CO) and free iron. Biliverdin and CO are gaining
particular interest because these two have been found to mediate most of anti
inflammatory, antioxidant and anti-apoptotic effects of HO-1. Although
extensively studied in different kinds of cancers and cardiovascular conditions,
role of HO-1 in diabetic neuropathy is still under investigation. In this paper,
we review the unique therapeutic potential of HO-1 and its role in mitigating
various pathological processes that lead to diabetic neuropathy. This review also
highlights the therapeutic approaches such as pharmacological and natural
inducers of HO-1, gene delivery of HO-1 or its reaction products that in future,
could lead to progression of HO-1 activators through the preclinical stages of
drug development to clinical trials.
PMID- 26432958
TI - Reconstruction of the Nasoseptal L-Strut in Rhinoplasty.
PMID- 26432959
TI - Binding studies of hydroxylated Multi-Walled Carbon Nanotubes to hemoglobin,
gamma globulin and transferrin.
AB - Biocompatibility of nanoparticles depends on their binding behavior with
biomolecules. Herein, we have reported the interaction of three different
biological macromolecules such as hemoglobin, gamma globulin and transferrin with
hydroxyl group functionalized Multi-Walled Carbon Nanotubes (OH-MWCNTs). Multiple
spectroscopic methods were utilized to identify the binding cum structural
changes in biomolecules upon their interaction. Hyperchromic effect observed in
the UV-visible spectra, and the quenching behavior from fluorescence emission
evidences the existence of bio-nanotube complex formation. Synchronous and three
dimensional fluorescence spectra of biomolecules, in correspondence with Trp and
Tyr residues showed the possible disturbance towards their aromatic micro
environment. Changes observed in the FTIR and FT-Raman amide bands, and amino
acid residue position of biomolecules upon interaction with CNTs showed the
possible effect towards their secondary structure. Further studies with CD
spectroscopy indicated the loss of alpha-helical structures quantitatively. The
study remains significant in evaluating the biosafety profile of functionalized
MWCNTs for their in vivo biomedical applications.
PMID- 26432960
TI - Palladium-Catalyzed Thioetherification of Quinolone Derivatives via
Decarboxylative C-S Cross-Couplings.
AB - A highly efficient and practical procedure for palladium-catalyzed direct
thioetherification of quinolone derivatives with diaryl disulfides through
decarboxylative C-S coupling has been established. The reaction could proceed
smoothly under air in the presence of Pd(OAc)2 and Ag2 CO3 in DMSO. This protocol
provides an appealing alternative to existing approaches to construct aryl
sulfides of quinolone derivatives, which may be used as key intermediates in the
synthesis of drug candidates.
PMID- 26432961
TI - Robotic and Open Radical Prostatectomy: Celebrating Oncologic Equivalence.
PMID- 26432962
TI - Legends in Urology.
PMID- 26432963
TI - Epigenetics application in the diagnosis and treatment of bladder cancer.
AB - INTRODUCTION: Bladder cancer is the sixth most common cancer in the Western
world. Patients with bladder cancer require close monitoring, which may include
frequent cystoscopy and urine cytology. Such monitoring results in significant
health care cost. The application of epigenetics may allow for a risk adapted
approach and more cost-effective method of monitoring. A number of epigenetic
changes have been described for many cancer sites, including the urinary bladder.
In this review, we discuss the use of epigenetics in bladder cancer and the
potential diagnostic and therapeutic applications. MATERIALS AND METHODS: A
comprehensive search of the English medical literature was conducted in PubMed
using the terms microRNA regulation, DNA methylation, histone modification and
bladder cancer. RESULTS: The most important epigenetic changes include DNA
methylation, histone modification and microRNA regulation. Both DNA
hypomethylation and hypermethylation have been associated with higher rate of
cancer. The association of epigenetic changes with bladder cancer has led to the
research of its diagnostic and prognostic implications as well as to the
development of novel drugs to target these changes with the aim of achieving a
survival benefit. CONCLUSIONS: Recently, epigenetics has been shown to play a
much greater role than previously anticipated in the initiation and propagation
of many tumors. The use of epigenetics for the diagnosis and treatment of bladder
cancer is an evolving and promising field. The possibility of reversing
epigenetic changes may facilitate additional cancer treatment options in the
future.
PMID- 26432964
TI - Validation of the lower urinary tract symptom score.
AB - INTRODUCTION: To develop and validate a lower urinary tract symptom score (LUTSS)
as a measure of lower urinary tract symptom (LUTS) severity and a treatment
outcome tool in adults. MATERIALS AND METHODS: An expert panel was convened to
develop the LUTSS questionnaire. Content validity was achieved by obtaining
subject and expert feedback from two prospective drafts. Subjects were divided
into three groups: normal, LUTS and overactive bladder (OAB). Questionnaire was
administered on two separate occasions within 1-2 weeks. Test-retest reliability,
internal consistency, discriminant validity, criterion validity and
responsiveness to change were also assessed. RESULTS: The questionnaire contains
14 questions with answers scored on a 5-point Likert scale (0-4). It includes 9
storage, 4 voiding and 1 bother question. One hundred ninety-one patients
completed it; 80 males and 111 females, mean age 65 years (range 22-91). Seventy
two had OAB, 91 LUTS without OAB and 28 were normal. Test-retest intraclass
correlation was 0.96 and Cronbach's-? was 0.77, indicating strong test-retest
reliability and internal consistency, respectively. ANOVA and post-hoc bootstrap
generated adjustments showed significant differences between the three groups (p
< 0.001), demonstrating discriminant validity. Responsiveness to change was
exhibited by the significant decrease between preop and postop scores and a
concurrent patient global impression of improvement (PGI-I) score indicative of
symptomatic improvement. CONCLUSION: The 14-question LUTSS is a validated
questionnaire that assesses a full range of LUTS in men and women. The ordinal
nature of the data with its highly specific description of symptoms makes it
ideally suited as a nuanced and comprehensive symptom score and patient reported
outcome (PRO) tool.
PMID- 26432965
TI - Impact of remote monitoring and supervision on resident training using new ACGME
milestone criteria.
AB - INTRODUCTION: The study objective was to determine the impact of remote
monitoring and supervision (RMS) in integrated endourology suites (IES) on
residents achieving endoscopic training milestones. MATERIALS AND METHODS: Twenty
one urology residents evaluated RMS in IES using a 25-question survey. IES
provided audio-visual communication for faculty to supervise residents remotely.
Questionnaire used a linear visual scale of 1-10 to assess acceptability (8
questions), impact on training (10 questions), supervision level (1 question),
and pre- and post-training milestone self-assessments (6 questions). Improvements
in Patient Care Milestone #7 (upper/lower tract endoscopic procedures) and
Patient Care Milestone #9 (office-based procedures) were analyzed. RESULTS:
Twenty-one urology residents (out of potential 23) evaluated RMS in IES using a
25-question survey (91.3% response rate). Overall RMS acceptability and
satisfaction was high (mean score = 9.1/10) with a majority (95.2%) feeling
comfortable being alone with the patient. Residents reported positively on the
following parameters: autonomy without compromising safety (8.7), supervision
level (8.6), achieving independence (8.4), education quality (8.3), learning rate
(8.1), clinical decision-making (8.0), and reducing case numbers to achieve
proficiency (7.6). Residents perceived no issues with under- or over-supervision,
and a majority (76.2%) expressed that RMS should be standard of training in
residency programs. Residents reported mean level increases of 2.5 and 2.8 (out
of 5) in Patient Care Milestones for endoscopic procedures and office-based
procedures, respectively (p < 0.0001). CONCLUSIONS: RMS in integrated endourology
suites may enhance resident education and endoscopic training. The study
demonstrated an increase in competency levels reported by residents trained using
RMS.
PMID- 26432966
TI - Association of quantitative magnetic resonance imaging parameters with
histological findings from MRI/ultrasound fusion prostate biopsy.
AB - INTRODUCTION: Purpose of this pilot study was to correlate quantitative
parameters derived from the multiparametric magnetic resonance imaging (MP-MRI)
of the prostate with results from MRI guided transrectal ultrasound (MRI/TRUS)
fusion prostate biopsy in men with suspected prostate cancer. MATERIALS AND
METHODS: Thirty-nine consecutive patients who had 3.0T MP-MRI and subsequent
MRI/TRUS fusion prostate biopsy were included and 73 MRI-identified targets were
sampled by 177 cores. The pre-biopsy MP-MRI consisted of T2-weighted, diffusion
weighted (DWI), and dynamic contrast enhanced (DCE) images. The association of
quantitative MRI measurements with biopsy histopathology findings was assessed by
Mann-Whitney U- test and Kruskal-Wallis test. RESULTS: Of 73 targets, biopsy
showed benign prostate tissue in 46 (63%), cancer in 23 (31.5%), and atypia/high
grade prostatic intraepithelial neoplasia in four (5.5%) targets. The median
volume of cancer-positive targets was 1.3 cm3. The cancer-positive targets were
located in the peripheral zone (56.5%), transition zone (39.1%), and seminal
vesicle (4.3%). Nine of 23 (39.1%) cancer-positive targets were higher grade
cancer (Gleason grade > 6). Higher grade targets and cancer-positive targets
compared to benign lesions exhibited lower mean apparent diffusion coefficient
(ADC) value (952.7 < 1167.9 < 1278.9), and lower minimal extracellular volume
fraction (ECF) (0.13 < 0.185 < 0.213), respectively. The difference in parameters
was more pronounced between higher grade cancer and benign lesions. CONCLUSIONS:
Our findings from a pilot study indicate that quantitative MRI parameters can
predict malignant histology on MRI/TRUS fusion prostate biopsy, which is a
valuable technique to ensure adequate sampling of MRI-visible suspicious lesions
under TRUS guidance and may impact patient management. The DWI-based quantitative
measurement exhibits a stronger association with biopsy findings than the other
MRI parameters.
PMID- 26432967
TI - Selling blood and gametes during tough economic times: insights from Google
search.
AB - INTRODUCTION: To use Google Insights search volume and publicly available
economic indicators to test the hypothesis that sperm, egg, and blood donations
increase during economic downturns and to demonstrate the feasibility of using
Google search volume data to predict national trends in actual sperm, egg, and
blood donations rates. MATERIALS AND METHODS: Cross-correlation statistical
analysis comparing Google search data for terms relating to blood, egg, and sperm
donations with various economic indicators including the S&P 500 closing values,
gross domestic product (GDP), the U.S. Index of Leading Indicators (U.S. Leading
Index), gross savings rate, mortgage interest rates, unemployment rate, and
consumer price index (CPI) from 2004-2011. A secondary analysis determined the
Pearson correlation coefficient between Google search data with actual sperm,
egg, and blood donation volume in the U.S. as measured by California Cryobank,
the National Assisted Reproductive Technology Surveillance System, and the
National Blood Collection and Utilization Survey, respectively. Significance of
cross-correlation and Pearson correlation analysis as indicated by p value.
RESULTS: There were several highly significant cross-correlation relationships
between search volume and various economic indicators. Correlation between Google
search volume for the term 'sperm donation,' 'egg donation,' and 'blood donation'
with actual number of sperm, egg and blood donations in the United States
demonstrated Pearson correlation coefficients of 0.2 (p > 0.10), -0.1 (p > 0.10),
and 0.07 (p > 0.10), respectively. Temporal analysis showed an improved
correlation coefficient of 0.9 (p < 0.05) for blood donation when shifted 12
months later relative to Google search volume. CONCLUSION: Google search volume
data for search terms relating to sperm, egg, and blood donation increase during
economic downturns. This finding suggests gamete and bodily fluid donations are
influenced by market forces like other commodities. Google search may be useful
for predicting blood donation trends but is more limited in predicting actual
semen and oocyte donation patterns.
PMID- 26432968
TI - Renal track creation for percutaneous nephrolithotomy: the history and relevance
of single stage dilation.
AB - INTRODUCTION: Percutaneous nephrolithotomy (PCNL) was described in the 1980s and
revolutionized the treatment of stone disease. The crucial component to this
surgery is satisfactory track creation. We examine how the development and
production in the 1980s of a single stage dilator (SSD) subsequently modified for
pediatric PCNL has become the ideal access tool for mini percutaneous
nephrolithotomy (mPCNL) today. MATERIALS AND METHODS: The conception, production,
scientific and clinical development of the original SSD is described. The
pitfalls of track dilation in general according to method of dilation are also
discussed and outlined. RESULTS: This study provides evidence clarifying commonly
held misconceptions about the origin of SSD which is the mainstay of the mPCNL
technique. CONCLUSIONS: Percutaneous renal surgery continues to evolve. In less
than 40 years stone surgery has transformed from a morbid open operation to a
number of minimally invasive, routine techniques. The SSD has been an innovation
that has played a crucial role in this change.
PMID- 26432969
TI - Aspirin and clopidogrel during robotic partial nephrectomy, is it safe?
AB - INTRODUCTION: Continuation of antiplatelet medications through major urologic
surgery may increase the risk of intraoperative and postoperative bleeding
complications. However, withdrawal of antiplatelet therapy may place some
patients at high risk of serious cardiovascular or cerebrovascular complications.
We assess the feasibility of performing robotic partial nephrectomy (RPN) in
patients maintained on aspirin or dual antiplatelet therapy with aspirin and
clopidogrel. MATERIAL AND METHODS: Perioperative data was collected prospectively
on 230 subjects undergoing RPN enrolled in an IRB approved quality of life study.
We analyzed subjects who were maintained on either aspirin alone or both aspirin
and clopidogrel throughout the operative and perioperative period. RESULTS: Of
the 230 patients, six were identified who continued antiplatelet medication
throughout the perioperative period. Four patients were maintained on 81 mg of
aspirin and two patients continued aspirin and clopidogrel. Average RENAL score
was 7 with mean tumor size of 4.1 cm. There were no intraoperative complications
and no conversions to open surgery. Average estimated blood loss was 242 mL.
Ninety day complication rate was 33%. One patient had postoperative bleeding on
day 14 after restarting coumadin in addition to their aspirin. CONCLUSIONS: We
present a case series demonstrating that in carefully selected patients, RPN on
aspirin and clopidogrel is feasible and safe. This is the first report of
patients who underwent RPN while on both aspirin and clopidogrel.
PMID- 26432970
TI - Safety of perioperative subcutaneous heparin for partial nephrectomy.
AB - INTRODUCTION: The development of deep venous thrombosis (DVT) or pulmonary
embolism (PE) following urologic surgery is a life threatening, but largely
preventable complication. Patients undergoing partial nephrectomy are at
increased risk for the development of DVT or PE as they often possess multiple
risk factors including malignancy, advanced age, and prolonged surgical time.
This risk can be significantly reduced by administration of perioperative
subcutaneous heparin (SQH), however many surgeons feel this is contraindicated
due to potential blood loss and related complications. MATERIALS AND METHODS: The
medical records of 293 consecutive patients undergoing planned open,
laparoscopic, or robotic assisted partial nephrectomy by a single surgeon over a
7 year period were reviewed. Approximately halfway through the period, the
standard DVT prevention practice was changed from sequential compression
stockings and early ambulation to include 5000 units of SQH administered 30-60
minutes prior to incision and continuing every 8 hours until discharge. RESULTS:
A total of 158 patients received perioperative SQH. There was no significant
difference in surgical blood loss, transfusions, operative time, change in pre to
postoperative hemoglobin or creatinine, conversion to radical nephrectomy, or
duration of stay between the groups. There were no DVTs in either group. There
was one PE in the group receiving SQH which was incidentally discovered.
CONCLUSIONS: Patients undergoing renal surgery for cancer are at increased risk
for the development of DVT and PE. Prophylaxis against this serious complication
with perioperative SQH is safe in patients undergoing partial nephrectomy despite
common surgeon concerns regarding blood loss and related complications.
PMID- 26432971
TI - Pediatric sutureless circumcision: an effective and cost efficient alternative.
AB - INTRODUCTION: Circumcision is the most commonly performed surgical procedures in
male children. Maine is one of 18 states in the United States which does not pay
for neonatal circumcisions. The aim of this study was to perform outcomes and
cost analysis of a sutureless circumcision technique versus circumcision using
sutures. Specifically, we evaluated Dermaflex (2-octyl cyanoacrylate, 2-OCA)
surgical glue circumcision as a cost effective, faster, and safe alternative to
traditional suture circumcision. MATERIALS AND METHODS: Our study was a non
randomized series. We collected the operative details prospectively, abstracted
clinical outcomes retrospectively, and performed data analysis retrospectively.
One hundred and twenty-six circumcisions were performed by two pediatric
urologists over a 1 year period. Suture circumcisions were performed exclusively
during the first 6 months, and 2-OCA glue circumcisions were performed during the
second 6 months. Billing charges were analyzed to extrapolate variable costs
between the two surgical procedures. The technique used to perform the sutureless
circumcision was a modification of the standard sleeve technique, with the use of
monopolar diathermy instead of scalpel, and application of 2-OCA glue to
approximate tissue edges. RESULTS: From Jan 2013 to Jan 2014, 72 patients
underwent circumcision with suture, and 54 patients underwent circumcision with 2
OCA glue. Mean age in the glue group was 61 months (range 8-202 months), and 50
months in the suture group (range 5-215 months), p = 0.19. All cases were
performed under general anesthesia, as outpatient surgery. Mean operative cut
time was 18.4 min for the glue group, and 28.6 min for the suture group (p <
0.01). The 10.2 min operative time difference translated to a $378 cost savings
per glue circumcision case. Complication rates were not statistically significant
between the two groups. CONCLUSION: The use of 2-OCA tissue adhesive for
sutureless circumcision is an alternative to the standard technique. It results
in faster operative times, with a significant cost savings, while maintaining
comparable complication rates to the standard suture technique. This is a viable,
less expensive surgical option for patients whose circumcisions are not covered
by Medicaid.
PMID- 26432972
TI - Retropubic prostatectomy for giant benign prostatic hyperplasia.
AB - Giant benign prostatic hyperplasia is a rare pathology of the prostate gland.
Here we report the successful removal of the ninth largest prostate ever
reported. This 65-year-old patient presented with acute urinary retention
secondary to a bulky left prostatic mass identified on pelvic magnetic resonance
imaging (MRI). His preoperative prostate-specific antigen (PSA) value was 44
ng/mL; preoperative biopsies were negative for malignancy. Open radical
retropubic prostatectomy was performed and the resulting prostatic mass was
measured at 13.5 cm x 11.5 cm x 5.2 cm, weighing 708 g including the prostate.
The patient tolerated the procedure well. Surgical pathology showed no evidence
of malignancy.
PMID- 26432973
TI - Not all penile cancers are created equal.
AB - Warty carcinoma variant of squamous cell carcinoma of the penis is a rare
condition, making up 7% to 10% of all penile carcinomas. We present a case of
warty carcinoma variant of squamous cell carcinoma of the penis in a 43-year-old
Caucasian. The tumor presented in a locally invasive manner, requiring a total
penectomy. The primary lesion measured over 15 cm x 16 cm, covering the entire
perineum. The clinical features, diagnosis, surgical treatment and pathology are
reviewed. In light of the locally invasive nature of warty carcinoma of the penis
and high recurrence rate, early diagnosis and aggressive treatment is necessary
for this type of unique penile cancer.
PMID- 26432974
TI - Multiple intra-renal artery aneurysms causing renal obstruction managed with
radical nephrectomy.
AB - A 46-year-old male with a history of hypertension presented with symptoms of
persistent abdominal fullness and a non-pulsatile abdominal mass. Subsequent
computed tomographic angiography studies revealed the presence multiple large
renal aneurysms from the segmental branches of the renal artery and an enlarged
hydronephrotic kidney with minimal parenchyma. The renal deterioration appeared
to be as a result of an obstruction caused by the large intra-renal aneurysms at
the level of the renal calyces. Since the right kidney had no function, an open
radical nephrectomy was subsequently performed without complications at 3 months
follow up.
PMID- 26432975
TI - BK virus associated pronounced hemorrhagic cystoureteritis after bone marrow
transplantation.
AB - Ureteral stenosis due to reactivation of the BK virus (BKV) in a state of
immunodeficiency is very rare. More common is the appearance of a hemorrhagic
cystitis. This report not only shows bilateral ureteral stenosis after bone
marrow transplantation, but also presents severe complications as chronic pelvic
pain and impaired kidney function as well as irreparable damage to the whole
urinary tract leading to nephroureterectomy, subtrigonal cystectomy and
orthotopic ileal neobladder. Finally renal transplantation was required. To our
knowledge this is the first case in the literature where such a severe course of
BKV associated hemorrhagic cystoureteritis is described.
PMID- 26432976
TI - Abstracts of the Mid-Atlantic and New England Sections of the American Urological
Association Joint Annual Meeting. October 22-24, 2015, Paradise Island, Bahamas.
PMID- 26432977
TI - Effect of Controlled Deposition of ZnS Shell on the Photostability of CdTe
Quantum Dots as Studied by Conventional Fluorescence and FCS Techniques.
AB - The effect of one and two monolayers of ZnS shells on the photostability of CdTe
quantum dots (QDs) in aqueous and nonaqueous media has been studied by monitoring
the fluorescence behavior of the QDs under ensemble and single-molecule
conditions. ZnS capping of the CdTe QDs leads to significant enhancement of the
fluorescence brightness of these QDs. Considerable enhancement of the
photostability of the shell-protected QDs, including the suppression of
photoactivation, is also observed. Fluorescence correlation spectroscopy
measurements reveal an increase in the number of particles undergoing reversible
fluorescent on-off transitions in the volume under observation with increasing
excitation power; this effect is found to be more pronounced in the case of core
only QDs than for core-shell QDs.
PMID- 26432979
TI - Increasing severity of traumatic brain injury in early childhood is associated
with a progressive reduction in long-term serum thyroid-stimulating hormone
concentrations.
PMID- 26432978
TI - Finding the gap: revealing local disparities in coverage of maternal, newborn and
child health services in South Sudan using lot quality assurance sampling.
AB - OBJECTIVES: We adapted a rapid monitoring method to South Sudan, a new nation
with one of the world's highest maternal and child mortality rates, aiming to
assess coverage of maternal, neonatal and child health (MNCH) services at the
time of independence, and introducing a monitoring and evaluation system (M&E)
for equity-sensitive tracking of progress related to Millennium Development Goals
(MDG) 4 and 5 at national, state and county levels to detect local variability.
METHODS: We conducted a national cross-sectional household survey among women
from six client populations in all, but six of South Sudan's 79 counties. We used
lot quality assurance sampling (LQAS) to measure coverage with diverse MNCH
indicators to obtain information for national-, state- and county-level health
system management decision-making. RESULTS: National coverage of MNCH services
was low for all maternal and neonatal care, child immunisation, and child care
indicators. However, results varied across states and counties. Central Equatoria
State (CES), where the capital is located, showed the highest coverage for most
indicators (e.g. >=4 antenatal care visits range: 4.5% in Jonglei to 40.1% in
CES). Urban counties often outperformed rural ones. CONCLUSIONS: This adaptation
of LQAS to South Sudan demonstrates how it can be used in the future as an M&E
system to track progress of MDGs at national, state and county levels to detect
local disparities. Overall, our data reveal a desperate need for improving MNCH
service coverage in all states.
PMID- 26432980
TI - Aldehyde-modified proteins as mediators of early inflammation in atherosclerotic
disease.
AB - Inflammation is widely accepted to play a major role in atherosclerosis and other
cardiovascular diseases. However, the exact mechanism(s) by which inflammation
exerts its pathogenic effect remains poorly understood. A number of oxidatively
modified proteins have been associated with cardiovascular disease. Recently,
attention has been given to the oxidative compound of malondialdehyde and
acetaldehyde, two reactive aldehydes known to covalently bind and adduct
macromolecules. These products have been shown to form stable malondialdehyde
acetaldehyde (MAA) adducts that are reactive and induce immune responses. These
adducts have been found in inflamed and diseased cardiovascular tissue of
patients. Antibodies to these adducted proteins are measurable in the serum of
diseased patients. The isotypes involved in the immune response to MAA (i.e.,
IgM, IgG, and IgA) are predictive of atherosclerotic disease progression and
cardiovascular events such as an acute myocardial infarction or coronary artery
bypass grafting. Therefore, it is the purpose of this article to review the past
and current knowledge of aldehyde-modified proteins and their role in
cardiovascular disease.
PMID- 26432981
TI - Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced
lung injury via inhibition of phosphodiesterase 4.
AB - Oxidative stress caused by neutrophils is an important pathogenic factor in
trauma/hemorrhagic (T/H)-induced acute lung injury (ALI). Osthol, a natural
coumarin found in traditional medicinal plants, has therapeutic potential in
various diseases. However, the pharmacological effects of osthol in human
neutrophils and its molecular mechanism of action remain elusive. In this study,
our data showed that osthol potently inhibited the production of superoxide anion
(O2(*-)) and reactive oxidants derived therefrom as well as expression of CD11b
in N-formylmethionylleucylphenylalanine (FMLP)-activated human neutrophils.
However, osthol inhibited neutrophil degranulation only slightly and it failed to
inhibit the activity of subcellular NADPH oxidase. FMLP-induced phosphorylation
of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) was
inhibited by osthol. Notably, osthol increased the cAMP concentration and protein
kinase A (PKA) activity in activated neutrophils. PKA inhibitors reversed the
inhibitory effects of osthol, suggesting that these are mediated through cAMP/PKA
dependent inhibition of ERK and Akt activation. Furthermore, the activity of cAMP
specific phosphodiesterase (PDE) 4, but not PDE3 or PDE7, was significantly
reduced by osthol. In addition, osthol reduced myeloperoxidase activity and
pulmonary edema in rats subjected to T/H shock. In conclusion, our data suggest
that osthol has effective anti-inflammatory activity in human neutrophils through
the suppression of PDE4 and protects significantly against T/H shock-induced ALI
in rats. Osthol may have potential for future clinical application as a novel
adjunct therapy to treat lung inflammation caused by adverse circulatory
conditions.
PMID- 26432983
TI - Symptoms of anxiety and depression in school-aged children with active epilepsy:
A population-based study.
AB - METHODS: Children (5-15 years) with active epilepsy were screened using the
parent-report (n=69) and self-report (n=48) versions of the Spence Children's
Anxiety Scale (SCAS) and the self-report version of the Children's Depression
Inventory (CDI) (n=48) in a population-based sample. RESULTS: A total of 32.2% of
children (self-report) and 15.2% of children (parent-report) scored >=1 SD above
the mean on the SCAS total score. The subscales where most difficulty were
reported on parent-report were Physical Injury and Separation Anxiety. There was
less variation on self-report. On the CDI, 20.9% of young people scored >=1 SD
above the mean. Children reported significantly more symptoms of anxiety on the
SCAS total score and three of the subscales (p<.05). There was a significant
effect on the SCAS total score of respondents by seizure type interaction,
suggesting higher scores on SCAS for children with generalized seizures on self-
but not parent-report. Higher CDI scores were significantly associated with
generalized seizures (p>.05). SUMMARY: Symptoms of anxiety were more common based
on self-report compared with parent-report. Children with generalized seizures
reported more symptoms of depression and anxiety.
PMID- 26432982
TI - Molecular weaponry: diverse effectors delivered by the Type VI secretion system.
AB - The Type VI secretion system is a widespread bacterial nanomachine, used to
deliver toxins directly into eukaryotic or prokaryotic target cells. These
secreted toxins, or effectors, act on diverse cellular targets, and their action
provides the attacking bacterial cell with a significant fitness advantage,
either against rival bacteria or eukaryotic host organisms. In this review, we
discuss the delivery of diverse effectors by the Type VI secretion system, the
modes of action of the so-called 'anti-bacterial' and 'anti-eukaryotic'
effectors, the mechanism of self-resistance against anti-bacterial effectors and
the evolutionary implications of horizontal transfer of Type VI secretion system
associated toxins. Whilst it is likely that many more effectors remain to be
identified, it is already clear that toxins delivered by this secretion system
represent efficient weapons against both bacteria and eukaryotes.
PMID- 26432985
TI - Lateral wedge insoles for people with medial knee osteoarthritis: one size fits
all, some or none?
PMID- 26432984
TI - The relationship between smoking and knee osteoarthritis in the Osteoarthritis
Initiative.
AB - OBJECTIVE: To estimate the extent that smoking history is associated with
symptoms and disease progression among individuals with radiographically
confirmed knee Osteoarthritis (OA). METHOD: Both cross-sectional (baseline) and
longitudinal studies employed data from the Osteoarthritis Initiative (OAI) (n =
2250 participants). Smoking history was assessed at baseline with 44% current or
former smokers. The Western Ontario and McMaster Universities Arthritis Index
(WOMAC) was used to measure knee pain, stiffness, and physical function. Disease
progression was measured using joint space width (JSW). We used adjusted
multivariable linear models to examine the relationship between smoking status
and exposure in pack years (PY) with symptoms and JSW at baseline. Changes in
symptoms and JSW over time were further assessed. RESULTS: In cross-sectional
analyses, compared to never-smokers high PY (>=15 PY) was associated with
slightly greater pain (beta 0.36, 95% CI: 0.01-0.71) and stiffness (beta 0.20,
95% CI: 0.03-0.37); and low PY (<15 PY) was associated with better JSW (beta
0.15, 95% CI: 0.02-0.28). Current smoking was associated with greater pain (beta
0.59, 95% CI: 0.04-1.15) compared to never-smokers. These associations were not
confirmed in the longitudinal study. Longitudinally, no associations were found
between high or low PY or baseline smoking status with changes in symptoms (at 72
months) or JSW (at 48 months). CONCLUSION: Cross-sectional findings are likely
due residual confounding. The more robust longitudinal analysis found no
associations between smoking status and symptoms or JSW. Long-term smoking
provides no benefits to knee OA patients while exposing them to other well
documented serious health risks.
PMID- 26432986
TI - Primary care physicians' perceptions about and confidence in deciding which
patients to refer for total joint arthroplasty of the hip and knee.
AB - OBJECTIVE: The purpose of this study is to examine the perceptions of primary
care physicians (PCPs) regarding indications, contraindications, risks and
benefits of total joint arthroplasty (TJA) and their confidence in selecting
patients for referral for TJA. DESIGN: PCPs recruited from among those providing
care to participants in an established community cohort with hip or knee
osteoarthritis (OA). Self-completed questionnaires were used to collect
demographic and practice characteristics and perceptions about TJA. Confidence in
referring appropriate patients for TJA was measured on a scale from 1 to 10;
respondents scoring in the lowest tertile were considered to have 'low
confidence'. Descriptive analyses were conducted and multiple logistic regression
was used to determine key predictors of low confidence. RESULTS: 212 PCPs
participated (58% response rate) (65% aged 50+ years, 45% female, 77% >15 years
of practice). Perceptions about TJA were highly variable but on average, PCPs
perceived that a typical surgical candidate would have moderate pain and
disability, identified few absolute contraindications to TJA, and overestimated
both the effectiveness and risks of TJA. On average, PCPs indicated moderate
confidence in deciding who to refer. Independent predictors of low confidence
were female physicians (OR = 2.18, 95% confidence interval (CI): 1.06-4.46) and
reporting a 'lack of clarity about surgical indications' (OR = 3.54, 95% CI: 1.87
6.66). CONCLUSIONS: Variability in perceptions and lack of clarity about surgical
indications underscore the need for decision support tools to inform PCP -
patient decision making regarding referral for TJA.
PMID- 26432987
TI - Focused electron beam induced deposition as a tool to create electron vortices.
AB - Focused electron beam induced deposition (FEBID) is a microscopic technique that
allows geometrically controlled material deposition with very high spatial
resolution. This technique was used to create a spiral aperture capable of
generating electron vortex beams in a transmission electron microscope (TEM). The
vortex was then fully characterized using different TEM techniques, estimating
the average orbital angular momentum to be ~0.8h per electron with almost 60% of
the beam ending up in the l=1 state.
PMID- 26432988
TI - Phosphoenolpyruvate carboxykinase and gluconeogenesis in grape pericarp.
AB - Glycolysis from sugars is necessary at all stages of development of grape
pericarp, and this raises the question as to why gluconeogenesis from malate
occurs. Phosphoenolpyruvate carboxykinase (PEPCK) is required for gluconeogenesis
in grape pericarp. In this study we determined the abundance of PEPCK protein and
activity in different parts of grape pericarp during its development. Both PEPCK
protein and activity were present throughout development, however, in both the
skin and the flesh their abundance increased greatly at the start of ripening.
This coincided with the onset of the decrease in the malate content of the berry.
The location of PEPCK in the pericarp at different stages of development was
determined using both immunohistochemistry and dissection. We provide a possible
explanation for the occurrence of gluconeogenesis in grape pericarp.
PMID- 26432989
TI - Fast detection of both O157 and non-O157 shiga-toxin producing Escherichia coli
by real-time optical immunoassay.
AB - Among bacterial pathogens involved in food-illnesses, seven serogroups (O26, O45,
O103, O111, O121, O145 and O157) of Shiga-toxin producing Escherichia coli
(STEC), are frequently identified. During such outbreak, and due to the
perishable property of most foodstuff, the time laps for the identification of
contaminated products and pathogens is thus critical to better circumvent their
spread. Traditional detection methods using PCR or culture plating are time
consuming and may present some limitations. In this study, we present a
multiplexed immunoassay for the optical detection of most commonly
enterohemorrhagic E. coli serogroups: O26, O45, O103, O111, O121, O145 and
O157:H7 in a single device. The use of Surface Plasmon Resonance imaging not only
enabled the label-free analysis of the samples but gave results in a real-time
manner. A dedicated protocol was set up for the detection of both low
contaminating bacterial concentrations of food samples (5 CFU per 25 g) and
postenrichment aliquots. By combining one single device for the detection of O157
and non-O157 STEC in a label-free manner, this rapid approach may have an
important economic and societal impact. SIGNIFICANCE AND IMPACT OF THE STUDY:
This article presents a simple-to-operate immunoassay for the specific detection
of Shiga-toxin producing Escherichia coli (STEC). This approach consists in the
on-chip assay detection of viable cells on a specifically designed antibody
microarray. By skipping any enrichment step and avoiding the use of labelling
agent, this approach based on the Surface Plasmon Resonance imaging of the
microarrays turns out to be much faster and more cost effective by comparison
with standardized methods.
PMID- 26432990
TI - Single and cartel effect of pesticides on biochemical and haematological status
of Clarias batrachus: A long-term monitoring.
AB - Pesticide mixtures are common in the streams of agricultural or urban catchments.
Individual and cartel toxicity of four different pesticides, namely Endosulfan,
Carbofuran, Methyl parathion and Cypermethrin were studied. Sub acute exposure
(1/10th of LC50) for 1, 7, 15, 30 and 60 days in Clarias batrachus active tissues
such as brain, gills, blood and liver were evaluated. Growth, hepatosomatic index
and survival performance were decreased, inhibition of brain
acetylcholinesterase, gills Na(+)/K(+) ATPase activities, and abnormal behavior
are noticed. The characteristics of the blood respiratory burst activity,
erythrocyte count, contents of hematocrit and hemoglobin are dwindled. Plasma
total proteins and liver glycogen decreased whereas blood glucose and serum
creatinine, triglycerides are elevated. The immunological attributes such as
white blood cell count was elevated, whereas albumin, globulins and lysozyme
activity significantly decreased. Hepatic superoxide dismutase, catalase and
glutathione S-transferase activities and lipid peroxidation levels are elevated,
whereas glutathione peroxidase and glutathione are reduced. Toxicity effect of
pesticides reached to a crest on 30th day and showed a descent thereafter except
in endosulfan which mounted its detrimental effect throughout the experimental
period. Toxicity trends of the present study are determined to be highest in Mix
group followed by cypermethrin, methyl parathion and carbofuran. Indiscriminate
application of these chemicals pose a toxic threat to non-target organisms,
damage the ecosystems and jeopardizes human health.
PMID- 26432991
TI - What are the differences in driver injury outcomes at highway-rail grade
crossings? Untangling the role of pre-crash behaviors.
AB - Crashes at highway-rail grade crossings can result in severe injuries and
fatalities to vehicle occupants. Using a crash database from the Federal Railroad
Administration (N=15,639 for 2004-2013), this study explores differences in
safety outcomes from crashes between passive controls (Crossbucks and STOP signs)
and active controls (flashing lights, gates, audible warnings and highway
signals). To address missing data, an imputation model is developed, creating a
complete dataset for estimation. Path analysis is used to quantify the direct and
indirect associations of passive and active controls with pre-crash behaviors and
crash outcomes in terms of injury severity. The framework untangles direct and
indirect associations of controls by estimating two models, one for pre-crash
driving behaviors (e.g., driving around active controls), and another model for
injury severity. The results show that while the presence of gates is not
directly associated with injury severity, the indirect effect through stopping
behavior is statistically significant (95% confidence level) and substantial.
Drivers are more likely to stop at gates that also have flashing lights and
audible warnings, and stopping at gates is associated with lower injury severity.
This indirect association lowers the chances of injury by 16%, compared with
crashes at crossings without gates. Similar relationships between other controls
and injury severity are explored. Generally, crashes occurring at active controls
are less severe than crashes at passive controls. The results of study can be
used to modify Crash Modification Factors (CMFs) to account for crash injury
severity. The study contributes to enhancing the understanding of safety by
incorporating pre-crash behaviors in a broader framework that quantifies
correlates of crash injury severity at active and passive crossings.
PMID- 26432992
TI - Screening and modular design for metabolic pathway optimization.
AB - Biological conversion of substrate sugars to a variety of products is an
increasingly popular option for chemical transformation due to its high
specificity and because of significant interest in the use of renewable
feedstocks. However, pathway optimization through metabolic engineering is often
needed to make such molecules economically at a relevant scale. Employing
effective methods to search and narrow the immense pathway parameter space is
essential to meet performance metrics such as high titer, yield and productivity
with efficiency. This review focuses on two practices that increase the
likelihood of finding a more advantageous pathway solution: implementing a screen
to identify high producers and utilizing modular pathway design to streamline
engineering efforts. While screens seek to couple product titer with a high
throughput measurement output, modular design aims to rationally construct
pathways to allow parallel optimization of various units. Both of these
methodologies have proven widely successful in metabolic engineering, with
combinations of them resulting in synergistic enhancements to pathway
optimization. This review will particularly highlight their utility for
microbially derived acid and alcohol products, which are of interest as fuels and
value added products.
PMID- 26432993
TI - Antioxidant treatment ameliorates experimental diabetes-induced depressive-like
behaviour and reduces oxidative stress in brain and pancreas.
AB - Studies have shown a relationship between diabetes mellitus (DM) and the
development of major depressive disorder. Alterations in oxidative stress are
associated with the pathophysiology of both diabetes mellitus and major
depressive disorder. This study aimed to evaluate the effects of antioxidants N
acetylcysteine and deferoxamine on behaviour and oxidative stress parameters in
diabetic rats. To this aim, after induction of diabetes by a single dose of
alloxan, Wistar rats were treated with N-acetylcysteine or deferoxamine for 14
days, and then depressive-like behaviour was evaluated. Oxidative stress
parameters were assessed in the prefrontal cortex, hippocampus, amygdala, nucleus
accumbens and pancreas. Diabetic rats displayed depressive-like behaviour, and
treatment with N-acetylcysteine reversed this alteration. Carbonyl protein levels
were increased in the prefrontal cortex, hippocampus and pancreas of diabetic
rats, and both N-acetylcysteine and deferoxamine reversed these alterations.
Lipid damage was increased in the prefrontal cortex, hippocampus, amygdala and
pancreas; however, treatment with N-acetylcysteine or deferoxamine reversed lipid
damage only in the hippocampus and pancreas. Superoxide dismutase activity was
decreased in the amygdala, nucleus accumbens and pancreas of diabetic rats. In
diabetic rats, there was a decrease in catalase enzyme activity in the prefrontal
cortex, amygdala, nucleus accumbens and pancreas, but an increase in the
hippocampus. Treatment with antioxidants did not have an effect on the activity
of antioxidant enzymes. In conclusion, animal model of diabetes produced
depressive-like behaviour and oxidative stress in the brain and periphery.
Treatment with antioxidants could be a viable alternative to treat behavioural
and biochemical alterations induced by diabetes.
PMID- 26432994
TI - Correlation of diffusion tensor and dynamic susceptibility contrast MRI with DNA
ploidy and cell cycle analysis of gliomas.
AB - OBJECTIVES: Flow cytometry provides a powerful tool to assess cells in G0/G1, S
and G2/M phase and ploidy. The purpose of the present study was to investigate
the correlation between diffusion tensor (DTI) and dynamic susceptibility
contrast (DSC) MRI metrics with cell cycle analysis findings in gliomas. PATIENTS
AND METHODS: We studied thirty patients who were operated on for glioma. DTI and
DSC MRI were performed within a week prior to surgical excision. Lesion/normal
ratios were calculated for the ADC, FA and rCBV. In an excised tumour sample flow
cytometric analysis was performed. RESULTS: There were 24 glioblastomas, 2
anaplastic astrocytomas, 1 oligoastrocytoma and 3 diffuse astrocytomas. There
were significant differences between low and high-grade gliomas for rCBV and ADC
values. Low grade tumours had higher G0/G1 phase fraction and lower S-phase,
G2/M, S+G2/M and S+G2/M/G0/G1 fractions There was a significant negative
correlation between rCBV and G0/G1 phase fraction and a positive correlation with
G2/M, S+G2/M and the S+G2/M/G0/G1 fraction. Significant correlation was also
observed between FA ratio and S+G2/M/G0/G1. There was a negative significant
correlation between ADC and S+G2/M and the S+G2/M/G0/G1 fraction. There were 21
(70%) diploid and 9 (30%) aneuploid tumours. No significant difference was found
between diploid and aneuploid tumours with respect to rCBV, ADC and FA values.
CONCLUSION: Dynamic susceptibility contrast MRI and diffusion tensor imaging
metrics are correlated to tumour aggressiveness as assessed by cell cycle
analysis.
PMID- 26432995
TI - Fluorescein sodium-guided surgery in cerebral lymphoma.
AB - OBJECTIVES: Growth and progress of primary central nervous lymphoma (PCNSL)
severely disrupt the blood brain barrier (BBB). Such disruptions can be
intraoperatively visualized by injecting fluorescein sodium (FL) and applying a
YELLOW 560 nm surgical microscope filter. Here, we report a small cohort of
patients with PCNSL that mimicked high grade gliomas (HGG) or cerebral metastases
(CM), who had been operated on with the use of FL. PATIENTS AND METHODS:
Retrospectively, seven patients with PCNSL were identified, who had been operated
on by means of microsurgery after intravenous FL injection. The surgical reports
were screened for statements on the grade of fluorescent staining in the tumor
area. One representative case was chosen to show the staining under white light
as well as under filtered light at different distances to the tumor area.
RESULTS: All patients had shown bright and homogenous fluorescent staining of the
tumor (n=7. 100%). No adverse effects had been observed. CONCLUSION: Similar to
patients with HGG or CM, patients with PCNSL may benefit from use of FL and the
dedicated YELLOW 560 nm filter in open surgery.
PMID- 26432996
TI - Targeted exome sequencing identified two novel truncation mutations in GPR98
causing Usher syndrome.
PMID- 26432997
TI - Sarcoidosis mimicking metastatic papillary thyroid cancer.
AB - INTRODUCTION: Sarcoidosis is a multisystemic, idiopathic disease. It has a highly
variable clinical course. It has been reported to present in association with
malignancy. Coexistence of sarcoidosis and thyroid cancer is rarely reported in
the literature. PRESENTATIOIN OF THE CASE: We present a case with neck swelling
for 3 months, and symmetrical painless thyroid enlargement without fixation to
deep tissues of the neck. Multiple nodules on the both thyroid lobes, hard
irregular, grade two goiter with lymphadenopathy all over anterior neck
compartments. Fine needle aspiration cytology was done under ultrasound guide
from right thyroid nodule and showed papillary thyroid carcinoma. Excisional
biopsy of the neck lymphnode showed picture typical for sarcoidosis. DISCUSSION:
Most researchers believe that patients with pulmonary sarcoidosis are predisposed
to develop malignancies, less than a dozen of cases are reported in the
literature to be associated with PTC with a very wide range of presentations and
clincal coarses. An interesting finding of our case is that in contrast to what
is reported, both diseases were not known by the physician until the time of
presentation. CONCLUSION: Cervical lymphadenopathy in association with goiter
could be metastasis, sarcoidosis or mixed, therefore should be seperately
biopsied.
PMID- 26432998
TI - A case of de Garengeot hernia: the feasibility of laparoscopic transabdominal
preperitoneal hernia repair.
AB - INTRODUCTION: de Garengeot hernia is described as the presence of an appendix in
a femoral hernia. This rare hernia usually presents with both diagnostic and
therapeutic dilemmas. PRESENTATION OF CASE: We report a case of a 59 year-old
woman with a one-year history of a right irreducible femoral hernia. She
underwent diagnostic laparoscopy with an intraoperative diagnosis of de Garengeot
hernia. This was followed by a laparoscopic transabdominal preperitoneal (TAPP)
approach for hernia repair. DISCUSSION: The long-standing presentation of de
Garengeot hernia is seldomly reported in literature. There has been no standard
approach of treatment for de Garengeot hernias described, possibly due to the
rarity of this condition. The unusual presentation of the hernia prompted us to
undergo a diagnostic laparoscopy first, during which the appendix was seen
incarcerated in a femoral hernia sac. We were easily able to proceed for a
laparoscopic TAPP approach for hernia repair without the need for conversion to
an open repair. CONCLUSION: We were able to obtain an accurate diagnosis of an
appendix within a long-standing irreducible femoral hernia through diagnostic
laparoscopy followed by transabdominal preperitoneal (TAPP) approach for hernia
repair. We would like to underline the usefulness of laparoscopy as a valuable
tool in the diagnosis and treatment of this unusual presentation of groin
hernias.
PMID- 26432999
TI - Letrozole-induced necrotising leukocytoclastic small vessel vasculitis: First
report of a case in the UK.
AB - INTRODUCTION: Letrozole, an aromatase inhibitor, is a commonly used neo-adjuvant
drug to treat hormone-sensitive breast cancer. There have been a few cases of
aromatase inhibitor induced vasculitis but the first case of letrozole-induced
vasculitis was reported from Switzerland in 2014 (Digklia et al.) [1].
PRESENTATION OF CASE: We report the case of a 72-year-old woman with a small
breast cancer. She was started on pre-operative letrozole (2.5mg/d) whilst
awaiting surgery. Ten days later she presented with burning pain and purpuric
skin lesions which progressed to extensive ischaemic superficial necrosis of the
lower limb skin, resolving over 3-4 months after local and systemic steroids.
Histologically, it showed leucocytoclasis with evidence of eosinophilia
consistent with a diagnosis of cutaneous leukocytoclastic small vessel
vasculitis. DISCUSSION: The initial clinical presentation was severe burning pain
around the ankles and a spreading violaceous rash. Letrozole was stopped. Wide
local excision (lumpectomy) and sentinel node biopsy were postponed because of
the accompanying pneumonitis and gastrointestinal upset, and were carried out 3.5
months later. Fortunately, the tumour size did not increase, but appeared to
reduce, and axillary lymph nodes remained negative, i.e., this patient's cancer
outcome does not seem to have been jeopardized. CONCLUSION: Leukocytoclastic
vasculitis is a hypersensitivity reaction that is usually self-resolving, though
our case needed systemic steroid treatment. Letrozole is a commonly used drug in
clinical practice and prescribers should be aware of this rare side effect, which
in our case delayed treatment without any apparent harm and possibly reduced
tumour size.
PMID- 26433000
TI - 15q11.2 microdeletion and hypoplastic left heart syndrome.
PMID- 26433001
TI - Autoimmune Diseases in the Bioinformatics Paradigm. Preface.
PMID- 26433002
TI - Comparison of a high-performance liquid chromatography method for quantification
of carbamazepine with chemiluminescent microparticle immunoassay.
AB - Carbamazepine is an antiepileptic drug widely used for the treatment of epilepsy.
In the National Institute of Neurology, monitoring has been performed using the
technique chemiluminescent microparticle immunoassay (CMIA) in an automated way
during the last five years. The aim of this study was to develop a simple and
rapid HPLC analytical method coupled to DAD-UV detection for the determination of
plasma concentrations of carbamazepine and compare its feasibility with those
used in routine analysis. The developed HPLC method was fully validated and the
applicability of the proposed method was verified through the analysis of plasma
samples of patients and later compared with the quantification of the same plasma
samples with the CMIA method. The limit of quantification obtained was 0.5
MUg/mL. The mean value for recovery was 99.05% and the coefficient of variation
(CV) was 5.6%. The precision and accuracy of this method were within the
acceptable limits; inter- and intraday CV values were <10%. The correlation
between the CMIA method and the developed HPLC method was very good (r ~ 0.999).
A Bland-Altman plot showed no significant bias between the results. The HPLC-DAD
method may be an alternative to determine and monitoring the carbamazepine levels
in human plasma or serum. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26433003
TI - 2-Oxoglutarate levels control adenosine nucleotide binding by Herbaspirillum
seropedicae PII proteins.
AB - Nitrogen metabolism in Proteobacteria is controlled by the Ntr system, in which
PII proteins play a pivotal role, controlling the activity of target proteins in
response to the metabolic state of the cell. Characterization of the binding of
molecular effectors to these proteins can provide information about their
regulation. Here, the binding of ATP, ADP and 2-oxoglutarate (2-OG) to the
Herbaspirillum seropedicae PII proteins, GlnB and GlnK, was characterized using
isothermal titration calorimetry. Results show that these proteins can bind three
molecules of ATP, ADP and 2-OG with homotropic negative cooperativity, and 2-OG
binding stabilizes the binding of ATP. Results also show that the affinity of
uridylylated forms of GlnB and GlnK for nucleotides is significantly lower than
that of the nonuridylylated proteins. Furthermore, fluctuations in the
intracellular concentration of 2-OG in response to nitrogen availability are
shown. Results suggest that under nitrogen-limiting conditions, PII proteins tend
to bind ATP and 2-OG. By contrast, after an ammonium shock, a decrease in the 2
OG concentration is observed causing a decrease in the affinity of PII proteins
for ATP. This phenomenon may facilitate the exchange of ATP for ADP on the ligand
binding pocket of PII proteins, thus it is likely that under low ammonium, low 2
OG levels would favor the ADP-bound state.
PMID- 26433004
TI - Prevalence of depression in Type 1 diabetes and the problem of over-diagnosis.
AB - AIMS: To determine the prevalence of depression and diabetes distress in adults
with Type 1 diabetes and the rate of false-positives when compared with rates of
major depressive disorder. METHODS: The sample consisted of 368 individuals with
Type 1 diabetes, aged > 19 years. Individuals completed: the eight-item Patient
Health Questionnaire depression scale (PHQ8), which was coded using four scoring
criteria (scores > 10, >12 and >15, and Diagnostic and Statistical Manual of
Mental Disorders 5 (DSM) algorithm scores); the Type 1 Diabetes Distress Scale;
and the Structured Clinical Interview for DSM Disorders (SCID) to assess major
depressive disorder. RESULTS: The prevalence rates of depression according to the
eight-item Patient Health Questionnaire were: score >10, 11.4%; score >12, 7.1%;
score >15, 3.8%; and positive algorithm result, 4.6%. The prevalence of major
depressive disorder was 3.5%; and the prevalence of at least moderate diabetes
distress was 42.1%. Depending on the criterion used, the false-positive rate when
using the Patient Health Questionnaire compared with the results when using the
SCID varied from 52 to 71%. Of those classified as depressed on the PHQ-8 or
Structured Clinical Interview for DSM Disorders, between 92.3 and 96.2% also
reported elevated diabetes distress. No significant association was found between
any group classed as having depression according to the PHQ8 or the SCID and
HbA1c concentration. Depression was significantly associated with more other life
stress, more complications and a lower level of education. CONCLUSIONS: We found
an unexpectedly low rate of current depression and major depressive disorder in
this diverse sample of adults with Type 1 diabetes, and a very high rate of false
positive results using the Patient Health Questionnaire. Considering the high
prevalence of diabetes distress, much of what has been considered depression in
adults with Type 1 diabetes may be attributed to the emotional distress
associated with managing a demanding chronic disease and other life stressors and
not necessarily to underlying psychopathology.
PMID- 26433005
TI - Phosphorus removal performance and speciation in virgin and modified argon oxygen
decarburisation slag designed for wastewater treatment.
AB - Argon oxygen decarburisation (AOD) slag may be used for phosphorus (P) removal,
as its high pH and weatherable calcium (Ca) minerals provide sufficient Ca(2+)
and OH(-) for calcium phosphate (Ca-PO4) precipitation. This study examined the P
removal performance of AOD slag for use as wastewater treatment material. Batch
experiments were carried out using both synthetic P solution and real wastewater,
followed by chemical modelling and X-ray absorption near edge structure (XANES)
spectroscopy. The influences of initial P concentration, slag dose and
modification by polyethylene glycol (PEG), an effective agent for generation of
porous materials, were investigated to determine the optimal conditions for P
removal by AOD slag. It was found that virgin AOD slag removed 94.8% of P from a
synthetic P solution in 4 h and 97.8% in 10 h. This high P removal was
accompanied by a rapid increase in pH from 7.0 to 10.74. The maximum P removal
capacity (PRC) from synthetic P solution ranged from 1.3 to 27.5 mg P g(-1). The
optimal AOD dose for P removal from wastewater, determined in 8-h batch
experiments, was 25 g L(-1). PEG modification increased the reaction rate and
resulted in higher final pH, increasing PRC by 47.9%. Combined Visual MINTEQ and
XANES analysis for detailed examination of P removal mechanisms revealed that the
main P removal mechanism was precipitation of calcium phosphate. According to the
XANES analysis, the main Ca-PO4 precipitate formed on virgin AOD slag under low
initial P concentration and high pH was apatite, while brushite was the dominant
product at high initial P concentration and low pH.
PMID- 26433006
TI - Interrogating chemical variation via layer-by-layer SERS during biofouling and
cleaning of nanofiltration membranes with further investigations into cleaning
efficiency.
AB - Periodic chemical cleaning is an essential step to maintain nanofiltration (NF)
membrane performance and mitigate biofouling, a major impediment in high-quality
water reclamation from wastewater effluent. To target the important issue of how
to clean and control biofouling more efficiently, this study developed surface
enhanced Raman spectroscopy (SERS) as a layer-by-layer tool to interrogate the
chemical variations during both biofouling and cleaning processes. The fact that
SERS only reveals information on the surface composition of biofouling directly
exposed to cleaning reagents makes it ideal for evaluating cleaning processes and
efficiency. SERS features were highly distinct and consistent with different
biofouling stages (bacterial adhesion, rapid growth, mature and aged biofilm).
Cleaning was performed on two levels of biofouling after 18 h (rapid growth of
biofilm) and 48 h (aged biofilm) development. An opposing profile of SERS bands
between biofouling and cleaning was observed and this suggests a layer-by-layer
cleaning mode. In addition, further dynamic biochemical and infrastructural
changes were demonstrated to occur in the more severe 48-h biofouling, resulting
in the easier removal of sessile cells from the NF membrane. Biofouling substance
dependent cleaning efficiency was also evaluated using the surfactant sodium
dodecyl sulfate (SDS). SDS appeared more efficient in cleaning lipid than
polysaccharide and DNA. Protein and DNA were the predominant residual substances
(irreversible fouling) on NF membrane leading to permanent flux loss. The
chemical information revealed by layer-by-layer SERS will lend new insights into
the optimization of cleaning reagents and protocols for practical membrane
processes.
PMID- 26433007
TI - Applying the polarity rapid assessment method to characterize nitrosamine
precursors and to understand their removal by drinking water treatment processes.
AB - Some N-nitrosamines (NAs) have been identified as emerging disinfection by
products during water treatment. Thus, it is essential to understand the
characteristics of the NA precursors. In this study, the polarity rapid
assessment method (PRAM) and the classical resin fractionation method were
studied as methods to fractionate the NA precursors during drinking water
treatment. The results showed that PRAM has much higher selectivity for NA
precursors than the resin approach. The normalized N-nitrosodimethylamine
formation potential (NDMA FP) and N-nitrosodiethylamine (NDEA) FP of four resin
fractions was at the same level as the average yield of the bulk organic matter
whereas that of the cationic fraction by PRAM showed 50 times the average. Thus,
the cationic fraction was shown to be the most important NDMA precursor
contributor. The PRAM method also helped understand which portions of the NA
precursor were removed by different water treatment processes. Activated carbon
(AC) adsorption removed over 90% of the non-polar PRAM fraction (that sorbs onto
the C18 solid phase extraction [SPE] cartridge) of NDMA and NDEA precursors. Bio
treatment removed 80-90% of the cationic fraction of PRAM (that is retained on
the cation exchange SPE cartridge) and 40-60% of the non-cationic fractions.
Ozonation removed 50-60% of the non-polar PRAM fraction of NA precursors and
transformed part of them into the polar fraction. Coagulation and sedimentation
had very limited removal of various PRAM fractions of NA precursors.
PMID- 26433008
TI - Economic evaluations of pharmacist-managed services in people with diabetes
mellitus: a systematic review.
AB - AIM: To review and evaluate the most recent literature on the economic outcomes
of pharmacist-managed services in people with diabetes. BACKGROUND: The global
prevalence of diabetes is increasing. Although pharmacist-managed services have
been shown to improve people's health outcomes, the economic impact of these
programmes remains unclear. METHODS: A systematic review was conducted of six
databases. Study inclusion criteria were: (1) original research; (2) evaluation
of pharmacist-managed services in people with diabetes; (3) an economic
evaluation; (4) English-language publication; and (5) full-text, published
between January 2006 and December 2014. The quality of the full economic
evaluations reviewed was evaluated using the Consolidated Health Economic
Evaluation Reporting Standards checklist. RESULTS: A total of 2204 articles were
screened and 25 studies were selected. These studies were conducted in a
community pharmacy (n = 10), a clinic- /hospital-based outpatient facility (n =
8), or others. Pharmacist-managed services included targeted education (n = 24),
general pharmacotherapeutic monitoring (n = 21), health screening or laboratory
testing services (n = 9), immunization services (n = 2) and pharmacokinetic
monitoring (n = 1). Compared with usual care, pharmacist-managed services
resulted in cost savings that varied from $7 to $65,000 ($8 to $85,000 in 2014 US
dollars) per person per year, and generated higher quality-adjusted life years
with lower costs. Benefit-to-cost ratios ranged from 1:1 to 8.5:1. Among the 25
studies reviewed, 11 were full economic evaluations of moderate quality.
CONCLUSIONS: Pharmacist-managed services had a positive return in terms of
economic viability. With the expanding role of pharmacists in the healthcare
sector, alongside increasing health expenditure, future economic studies of high
quality are needed to investigate the cost-effectiveness of these services.
PMID- 26433009
TI - Dairy consumption and risk of metabolic syndrome: a meta-analysis.
AB - AIMS: To conduct a systematic review and meta-analysis of epidemiological studies
in order to assess quantitatively the effect of dairy consumption on risk of
metabolic syndrome. METHODS: We searched for eligible studies published up to
March 2015 through the PubMed and Embase databases and reviewed the references of
relevant articles. Random-effects models were used to calculate the pooled
relative risks with 95% CIs after adjusting for several confounders. RESULTS: We
identified nine prospective cohort studies including a total of 35 379 subjects
and 7322 incident cases of metabolic syndrome, and 12 cross-sectional studies
including 37 706 subjects. In the meta-analysis of prospective cohort studies,
the pooled relative risk of incidence of metabolic syndrome for the highest vs.
the lowest category of dairy consumption was 0.85 (95% CI 0.73-0.98), and for a 1
serving/day increment of dairy consumption, the pooled relative risk was 0.88
(95% CI 0.82-0.95). In the meta-analysis of cross-sectional studies, the pooled
relative risk of prevalence of metabolic syndrome for the highest vs. the lowest
category of dairy consumption was 0.73 (95% CI 0.63-0.86). The association was
not significantly different by geographical region, follow-up time and adjustment
factors. CONCLUSION: Our findings indicate that dairy consumption is inversely
associated with the incidence and prevalence of metabolic syndrome. Further well
designed cohort studies and randomized controlled trials are warranted to provide
definitive evidence.
PMID- 26433010
TI - Recombination and horizontal transfer of nodulation and ACC deaminase (acdS)
genes within Alpha- and Betaproteobacteria nodulating legumes of the Cape Fynbos
biome.
AB - The goal of this work is to study the evolution and the degree of horizontal gene
transfer (HGT) within rhizobial genera of both Alphaproteobacteria
(Mesorhizobium, Rhizobium) and Betaproteobacteria (Burkholderia), originating
from South African Fynbos legumes. By using a phylogenetic approach and comparing
multiple chromosomal and symbiosis genes, we revealed conclusive evidence of high
degrees of horizontal transfer of nodulation genes among closely related species
of both groups of rhizobia, but also among species with distant genetic
backgrounds (Rhizobium and Mesorhizobium), underscoring the importance of lateral
transfer of symbiosis traits as an important evolutionary force among rhizobia of
the Cape Fynbos biome. The extensive exchange of symbiosis genes in the Fynbos is
in contrast with a lack of significant events of HGT among Burkholderia symbionts
from the South American Cerrado and Caatinga biome. Furthermore, homologous
recombination among selected housekeeping genes had a substantial impact on
sequence evolution within Burkholderia and Mesorhizobium. Finally, phylogenetic
analyses of the non-symbiosis acdS gene in Mesorhizobium, a gene often located on
symbiosis islands, revealed distinct relationships compared to the chromosomal
and symbiosis genes, suggesting a different evolutionary history and independent
events of gene transfer. The observed events of HGT and incongruence between
different genes necessitate caution in interpreting topologies from individual
data types.
PMID- 26433012
TI - DOCTORS' LIABILITY TO THE PATIENT'S RELATIVES IN GENETIC MEDICINE: ABC V St
George's Healthcare NHS trust[2015] EWHC 1394 (QB).
AB - This comment analyses the recent High Court's decision in ABC v St George's
Healthcare NHS Trust. In this case, the court struck out a claim brought by a
patient's daughter against her father's doctors for their failure to warn her of
his hereditary disease. The claimant argued that the doctors' failure caused her
harm and violated her rights under the European Convention on Human Rights. It is
argued in this comment that the judge should have accepted the claimant's
application.
PMID- 26433011
TI - The Role of Phospholipase D in Regulated Exocytosis.
AB - There are a diversity of interpretations concerning the possible roles of
phospholipase D and its biologically active product phosphatidic acid in the
late, Ca(2+)-triggered steps of regulated exocytosis. To quantitatively address
functional and molecular aspects of the involvement of phospholipase D-derived
phosphatidic acid in regulated exocytosis, we used an array of phospholipase D
inhibitors for ex vivo and in vitro treatments of sea urchin eggs and isolated
cortices and cortical vesicles, respectively, to study late steps of exocytosis,
including docking/priming and fusion. The experiments with fluorescent
phosphatidylcholine reveal a low level of phospholipase D activity associated
with cortical vesicles but a significantly higher activity on the plasma
membrane. The effects of phospholipase D activity and its product phosphatidic
acid on the Ca(2+) sensitivity and rate of fusion correlate with modulatory
upstream roles in docking and priming rather than to direct effects on fusion per
se.
PMID- 26433013
TI - How computer science can help in understanding the 3D genome architecture.
AB - Chromosome conformation capture techniques are producing a huge amount of data
about the architecture of our genome. These data can provide us with a better
understanding of the events that induce critical regulations of the cellular
function from small changes in the three-dimensional genome architecture.
Generating a unified view of spatial, temporal, genetic and epigenetic properties
poses various challenges of data analysis, visualization, integration and mining,
as well as of high performance computing and big data management. Here, we
describe the critical issues of this new branch of bioinformatics, oriented at
the comprehension of the three-dimensional genome architecture, which we call
'Nucleome Bioinformatics', looking beyond the currently available tools and
methods, and highlight yet unaddressed challenges and the potential approaches
that could be applied for tackling them. Our review provides a map for
researchers interested in using computer science for studying 'Nucleome
Bioinformatics', to achieve a better understanding of the biological processes
that occur inside the nucleus.
PMID- 26433014
TI - Caveolin-1 single-nucleotide polymorphism and arterial stiffness in non-dialysis
chronic kidney disease.
AB - BACKGROUND: Arteriosclerosis is an independent predictor of increased
cardiovascular mortality in chronic kidney disease (CKD). Histologically it is
characterized by hypertrophy and fibrosis of the arterial media wall leading to
increased arterial stiffness and end-organ damage. Caveolin-1 acts as an
intracellular signalling pathway chaperone in human fibrotic and vascular
diseases. The purpose of this study was to assess the association between
caveolin-1 (CAV1) single-nucleotide polymorphism (SNP) rs4730751 and arterial
stiffness as measured by arterial pulse wave velocity (PWV) in an early-stage CKD
cohort and in a cohort with more severe CKD. METHODS: Two prospectively
maintained patient cohorts with non-dialysis CKD were studied: 144 patients in
the Chronic Renal Impairment in Birmingham (CRIB) cohort and 147 patients in the
Renal Impairment in Secondary Care (RIISC) cohort, with matched exclusion
criteria and DNA sampling availability. At entry to each cohort database, each
patient's initial arterial PWV was measured, as well as their anthropomorphic and
biochemical data. CAV1 rs4730751 SNP genotyping was performed using Taqman
technology. RESULTS: The CAV1 rs4730751 SNP CC genotype was associated with lower
arterial PWV in both CRIB early stage CKD patients [8.1 versus 8.6 m/s;
coefficient -0.780 (-1.412, -0.149); P = 0.016] and RIISC more advanced stage CKD
patients [8.7 versus 9.4 m/s; coefficient -0.695 (-1.288, -0.102); P = 0.022];
these relationships held following adjustment for other important confounders.
CONCLUSIONS: This replicated study suggests potential utility of the studied CAV1
SNP as a genetic biomarker in CKD and a role for CAV1 in the development of
arteriosclerosis in this setting. Further studies are warranted to further
explore the basic science driving these clinical observations.
PMID- 26433016
TI - Possible role of trace elements in epilepsy and febrile seizures: a meta
analysis.
AB - Seizures are among the most common causes of apparent life-threatening events.
There are discrepancies among the published reports on the correlation between
epilepsy/febrile seizures and deficiency or overload of trace elements. The
objective of this review and meta-analysis was to examine the present knowledge
on the concentrations of the most investigated trace metals, including zinc,
copper, selenium, and magnesium, in patients with epilepsy and febrile seizures.
The PubMed and Scopus databases were searched to identify case-control studies
that compared the concentration of zinc, copper, magnesium, and selenium in
serum, hair, or cerebrospinal fluid between patients with epilepsy/febrile
seizures and controls. A total of 60 articles were included in the present study
(40 pertaining to epilepsy and 25 pertaining to febrile seizures). The serum
concentration of zinc in nontreated patients with epilepsy was significantly
higher than in controls (P = 0.034). There were significantly reduced serum
concentrations of zinc (P = 0.018) and selenium (P = 0.012) in patients with
febrile seizures compared with controls. The concentrations of copper, magnesium,
and zinc were all significantly altered in patients with epilepsy who received
antiepileptic drugs compared with untreated patients with epilepsy. Designing
treatments to selectively restore zinc levels may be a strategy for treating
patients with epilepsy. It is still unclear whether these ions are causal to, or
a cofactor in, the development of epilepsy. Knowledge of the effects of various
antiepileptic drugs on trace element homeostasis could potentially be used to
effectively guide appropriate therapeutic strategies in the future.
PMID- 26433015
TI - How complicated can it be? The link between APOL1 risk variants and lipoprotein
heterogeneity in kidney and cardiovascular diseases.
PMID- 26433017
TI - Evidence of the effectiveness of flour fortification programs on iron status and
anemia: a systematic review.
AB - CONTEXT: More than 80 countries fortify flour, yet the public health impact of
this intervention on iron and anemia outcomes has not been reviewed. OBJECTIVE:
The objective of this systematic review was to review published and gray
literature pertaining to the impact of flour fortification on iron and anemia.
DATA SOURCES: A systematic review was conducted by searching 17 databases and
appealing for unpublished reports, yielding 1881 documents. STUDY SELECTION: Only
studies of government-supported, widely implemented fortification programs in
which anemia or iron status was measured prior to and >=12 months after
initiation of fortification were included. DATA EXTRACTION: Details about the
design, coverage, compliance with national standards, and evaluation (e.g.,
anemia prevalence before and after fortification) of flour fortification programs
were extracted from the reports. DATA SYNTHESIS: Thirteen studies describing 26
subgroups (n = 14 for children <=15 y, n = 12 for women of reproductive age) were
included. During the period from pre- to postfortification (and as difference-in
difference for those studies that included a control group), there were
statistically significant decreases in the prevalence of anemia in 4 of 13
subgroups of children and in 4 of 12 subgroups of women of reproductive age as
well as significant decreases in the prevalence of low ferritin in 1 of 6
subgroups of children and in 3 of 3 subgroups of women of reproductive age.
CONCLUSIONS: . Evidence of the effectiveness of flour fortification for reducing
the prevalence of anemia is limited; however, evidence of effectiveness for
reducing the prevalence of low ferritin in women is more consistent.
PMID- 26433018
TI - The diameter growth-height growth relationship as related to the diameter-height
relationship.
PMID- 26433019
TI - The relationship between needle sugar carbon isotope ratios and tree rings of
larch in Siberia.
AB - Significant gaps still exist in our knowledge about post-photosynthetic leaf
level and downstream metabolic processes and isotopic fractionations. This
includes their impact on the isotopic climate signal stored in the carbon isotope
composition (delta(13)C) of leaf assimilates and tree rings. For the first time,
we compared the seasonal delta(13)C variability of leaf sucrose with intra
annual, high-resolution delta(13)C signature of tree rings from larch (Larix
gmelinii Rupr.). The trees were growing at two sites in the continuous permafrost
zone of Siberia with different growth conditions. Our results indicate very
similar low-frequency intra-seasonal trends of the sucrose and tree ring
delta(13)C records with little or no indication for the use of 'old'
photosynthates formed during the previous year(s). The comparison of leaf sucrose
delta(13)C values with that in other leaf sugars and in tree rings elucidates the
cause for the reported (13)C-enrichment of sink organs compared with leaves. We
observed that while the average delta(13)C of all needle sugars was 1.20/00 more
negative than delta(13)C value of wood, the delta(13)C value of the transport
sugar sucrose was on an average 1.00/00 more positive than that of wood. Our
study shows a high potential of the combined use of compound-specific isotope
analysis of sugars (leaf and phloem) with intra-annual tree ring delta(13)C
measurements for deepening our understanding about the mechanisms controlling the
isotope variability in tree rings under different environmental conditions.
PMID- 26433020
TI - Overexpression of gibberellin 20-oxidase1 from Pinus densiflora results in
enhanced wood formation with gelatinous fiber development in a transgenic hybrid
poplar.
AB - Gibberellins (GAs) are important regulators of plant shoot biomass growth, and GA
20-oxidase (GA20ox) is one of the major regulatory enzymes in the GA biosynthetic
pathway. Previously, we showed that the expression levels of a putative GA20ox1
(i.e., PdGA20ox1) in stem tissue of 3-month-old seedlings of 12 families of Pinus
densiflora were positively correlated with stem diameter growth across those same
families growing in an even-aged 32-year-old pine forest (Park EJ, Lee WY,
Kurepin LV, Zhang R, Janzen L, Pharis RP (2015) Plant hormone-assisted early
family selection in Pinus densiflora via a retrospective approach. Tree Physiol
35:86-94). To further investigate the molecular function of this gene in the stem
wood growth of forest trees, we produced transgenic poplar lines expressing
PdGA20ox1 under the control of the 35S promoter (designated as 35S::PdGA20ox1).
By age 3 months, most of the 35S::PdGA20ox1 poplar trees were showing an
exceptional enhancement of stem wood growth, i.e., up to fourfold increases in
stem dry weight, compared with the nontransformed control poplar plants.
Significant increases in endogenous GA1, its immediate precursor (GA20) and its
catabolite (GA8) in elongating internode tissue accompanied the increased stem
growth in the transgenic lines. Additionally, the development of gelatinous
fibers occurred in vertically grown stems of the 35S::PdGA20ox1 poplars. An
analysis of the cell wall monosaccharide composition of the 35S::PdGA20ox1
poplars showed significant increases in xylose and glucose contents, indicating a
qualitative increase in secondary wall depositions. Microarray analyses led us to
find a total of 276 probe sets that were upregulated (using threefold as a
threshold) in the stem tissues of 35S::PdGA20ox1 poplars relative to the
controls. 'Cell organization or biogenesis'- and 'cell wall'-related genes were
overrepresented, including many of genes that are involved in cell wall
modification. Several transcriptional regulators, which positively regulate cell
elongation through GA signaling, were also upregulated. In contrast, genes
involved in defense signaling were appreciably downregulated in the
35S::PdGA20ox1 stem tissues, suggesting a growth versus defense trade-off. Taken
together, our results suggest that PdGA20ox1 functions to promote stem growth and
wood formation in poplar, probably by activating GA signaling while
coincidentally depressing defense signaling.
PMID- 26433021
TI - Ponderosa pine resin defenses and growth: metrics matter.
AB - Bark beetles (Coleoptera: Curculionidae, Scolytinae) cause widespread tree
mortality in coniferous forests worldwide. Constitutive and induced host defenses
are important factors in an individual tree's ability to survive an attack and in
bottom-up regulation of bark beetle population dynamics, yet quantifying defense
levels is often difficult. For example, in Pinus spp., resin flow is important
for resistance to bark beetles but is extremely variable among individuals and
within a season. While resin is produced and stored in resin ducts, the specific
resin duct metrics that best correlate with resin flow remain unclear. The
ability and timing of some pine species to produce induced resin is also not well
understood. We investigated (i) the relationships between ponderosa pine (Pinus
ponderosa Lawson & C. Lawson) resin flow and axial resin duct characteristics,
tree growth and physiological variables, and (ii) if mechanical wounding induces
ponderosa pine resin flow and resin ducts in the absence of bark beetles. Resin
flow increased later in the growing season under moderate water stress and was
highest in faster growing trees. The best predictors of resin flow were
nonstandardized measures of resin ducts, resin duct size and total resin duct
area, both of which increased with tree growth. However, while faster growing
trees tended to produce more resin, models of resin flow using only tree growth
were not statistically significant. Further, the standardized measures of resin
ducts, density and duct area relative to xylem area, decreased with tree growth
rate, indicating that slower growing trees invested more in resin duct defenses
per unit area of radial growth, despite a tendency to produce less resin overall.
We also found that mechanical wounding induced ponderosa pine defenses, but this
response was slow. Resin flow increased after 28 days, and resin duct production
did not increase until the following year. These slow induced responses may allow
unsuccessfully attacked or wounded trees to resist future bark beetle attacks.
Forest management that encourages healthy, vigorously growing trees will also
favor larger resin ducts, thereby conferring increased constitutive resistance to
bark beetle attacks.
PMID- 26433022
TI - A quantitative framework for whole-body coordination reveals specific deficits in
freely walking ataxic mice.
AB - The coordination of movement across the body is a fundamental, yet poorly
understood aspect of motor control. Mutant mice with cerebellar circuit defects
exhibit characteristic impairments in locomotor coordination; however, the
fundamental features of this gait ataxia have not been effectively isolated. Here
we describe a novel system (LocoMouse) for analyzing limb, head, and tail
kinematics of freely walking mice. Analysis of visibly ataxic Purkinje cell
degeneration (pcd) mice reveals that while differences in the forward motion of
individual paws are fully accounted for by changes in walking speed and body
size, more complex 3D trajectories and, especially, inter-limb and whole-body
coordination are specifically impaired. Moreover, the coordination deficits in
pcd are consistent with a failure to predict and compensate for the consequences
of movement across the body. These results isolate specific impairments in whole
body coordination in mice and provide a quantitative framework for understanding
cerebellar contributions to coordinated locomotion.
PMID- 26433023
TI - Human observers have optimal introspective access to perceptual processes even
for visually masked stimuli.
AB - Many believe that humans can 'perceive unconsciously' - that for weak stimuli,
briefly presented and masked, above-chance discrimination is possible without
awareness. Interestingly, an online survey reveals that most experts in the field
recognize the lack of convincing evidence for this phenomenon, and yet they
persist in this belief. Using a recently developed bias-free experimental
procedure for measuring subjective introspection (confidence), we found no
evidence for unconscious perception; participants' behavior matched that of a
Bayesian ideal observer, even though the stimuli were visually masked. This
surprising finding suggests that the thresholds for subjective awareness and
objective discrimination are effectively the same: if objective task performance
is above chance, there is likely conscious experience. These findings shed new
light on decades-old methodological issues regarding what it takes to consider a
neurobiological or behavioral effect to be 'unconscious,' and provide a platform
for rigorously investigating unconscious perception in future studies.
PMID- 26433024
TI - What the [beep]? Six-month-olds link novel communicative signals to meaning.
AB - Over the first year, infants tune into the signals of their native language and
begin to link them to meaning. Here, we ask whether infants, like adults, can
also infer the communicative function of otherwise arbitrary signals (here, tone
sequences) and link these to meaning as well. We examined 6-month-olds' object
categorization in the context of sine-wave tones, a signal that fails to support
categorization at any point during their first year. However, before the
categorization task, we exposed infants to tones in one of two vignettes. In one,
the tones were produced by an actor in a rich communicative exchange; in the
other, infants heard the very same tones, but these were uncoupled from the
actors' activity. Infants exposed to the communicative vignette successfully
formed object categories in the subsequent test; those exposed to the non
communicative vignette failed, performing identically to infants with no prior
exposure to this novel signal. This reveals in 6-month-old infants a remarkable
flexibility in identifying which signals in the ambient environment are
communicative and in linking these signals to core cognitive capacities including
categorization.
PMID- 26433025
TI - Open ventral hernia repair using ProGrip self-gripping mesh.
AB - PURPOSE: Secure mesh fixation in incisional hernia repair is mandatory to prevent
mesh dislocation and possible recurrence. Traditional fixation methods have been
implicated as a source of chronic postoperative pain. We report 2-year outcomes
with a self-gripping mesh for open tension-free repair of large incisional
hernia. METHODS: This prospective case series enrolled 20 patients with large
primary incisional hernia (mean defect size: 84 cm(2)). Patients were electively
treated by a single surgeon using a macroporous polyester mesh with resorbable
polylactic acid microgrips (ProGrip, Covidien, Mansfield, MA, USA) using open
onlay technique. Main outcomes included pain severity, Carolinas Comfort Scale
(CCS), complications, and hernia recurrence. Patients returned for follow-up at
1, 3, 6, 12, and 24 months. RESULTS: Median mesh fixation time was 2 min. Mean
operative time was 38 min and blood loss was minimal (50 cc). Most patients (75%)
were discharged same day. The only perioperative complication was a minor seroma
in one patient. Patient follow-up compliance through 2 years was 100%. Mean pain
score was 1.8 at discharge, 0.9 at 1 month, 0.7 at 1 year, and 0 at 2 years. At 2
years, all patients were "very satisfied" with treatment and hernia-specific
quality of life was excellent (mean CCS score = 0). No infection, mesh removal,
or hernia recurrence occurred during follow-up. CONCLUSIONS: Open repair using a
self-gripping mesh is a viable treatment option in patients with large incisional
hernia. Immediate mesh fixation facilitates a safe and durable tension-free
repair.
PMID- 26433026
TI - Hepatitis delta virus facilitates the selection of hepatitis B virus mutants in
vivo and functionally impacts on their replicative capacity in vitro.
AB - To identify molecular interactions between hepatitis B virus (HBV) and hepatitis
delta virus (HDV), HBV sequences were analysed in HBV/HDV-infected patients.
Characteristic amino acid substitutions were found in cytosolic domains of
hepatitis B surface antigen (HBsAg), in contrast to HBV-mono-infected controls.
The functional impact of HDV on the replication of wild-type and mutant HBV was
assessed in vitro. HDV co-transfection significantly reduced the replication of
HBV strains containing precore or basal core promoter mutations, and HBV
polymerase or surface antigen mutants affected HDV replication in vitro.
Conclusively, our study revealed distinct HBsAg mutational patterns in HBV/HDV
infected patients and novel functional interactions between HBV and HDV.
PMID- 26433027
TI - Simultaneous determination of sample thickness, tilt, and electron mean free path
using tomographic tilt images based on Beer-Lambert law.
AB - Cryo-electron tomography (cryo-ET) is an emerging technique that can elucidate
the architecture of macromolecular complexes and cellular ultrastructure in a
near-native state. Some important sample parameters, such as thickness and tilt,
are needed for 3-D reconstruction. However, these parameters can currently only
be determined using trial 3-D reconstructions. Accurate electron mean free path
plays a significant role in modeling image formation process essential for
simulation of electron microscopy images and model-based iterative 3-D
reconstruction methods; however, their values are voltage and sample dependent
and have only been experimentally measured for a limited number of sample
conditions. Here, we report a computational method, tomoThickness, based on the
Beer-Lambert law, to simultaneously determine the sample thickness, tilt and
electron inelastic mean free path by solving an overdetermined nonlinear least
square optimization problem utilizing the strong constraints of tilt
relationships. The method has been extensively tested with both stained and cryo
datasets. The fitted electron mean free paths are consistent with reported
experimental measurements. The accurate thickness estimation eliminates the need
for a generous assignment of Z-dimension size of the tomogram. Interestingly, we
have also found that nearly all samples are a few degrees tilted relative to the
electron beam. Compensation of the intrinsic sample tilt can result in horizontal
structure and reduced Z-dimension of tomograms. Our fast, pre-reconstruction
method can thus provide important sample parameters that can help improve
performance of tomographic reconstruction of a wide range of samples.
PMID- 26433028
TI - A novel fully automatic scheme for fiducial marker-based alignment in electron
tomography.
AB - Although the topic of fiducial marker-based alignment in electron tomography (ET)
has been widely discussed for decades, alignment without human intervention
remains a difficult problem. Specifically, the emergence of subtomogram averaging
has increased the demand for batch processing during tomographic reconstruction;
fully automatic fiducial marker-based alignment is the main technique in this
process. However, the lack of an accurate method for detecting and tracking
fiducial markers precludes fully automatic alignment. In this paper, we present a
novel, fully automatic alignment scheme for ET. Our scheme has two main
contributions: First, we present a series of algorithms to ensure a high
recognition rate and precise localization during the detection of fiducial
markers. Our proposed solution reduces fiducial marker detection to a sampling
and classification problem and further introduces an algorithm to solve the
parameter dependence of marker diameter and marker number. Second, we propose a
novel algorithm to solve the tracking of fiducial markers by reducing the
tracking problem to an incomplete point set registration problem. Because a
global optimization of a point set registration occurs, the result of our
tracking is independent of the initial image position in the tilt series,
allowing for the robust tracking of fiducial markers without pre-alignment. The
experimental results indicate that our method can achieve an accurate tracking,
almost identical to the current best one in IMOD with half automatic scheme.
Furthermore, our scheme is fully automatic, depends on fewer parameters (only
requires a gross value of the marker diameter) and does not require any manual
interaction, providing the possibility of automatic batch processing of electron
tomographic reconstruction.
PMID- 26433029
TI - The giant keyhole limpet radular teeth: A naturally-grown harvest machine.
AB - The limpet radula is a feeding organ, which contains more than 100 rows of teeth.
During their growth the teeth mature and advance in position along the radula.
The simpler doccoglossan radulae operate by grinding rocky substrates, extracting
the algae by rasping and scraping with the teeth functioning as shovels. Less is
known about the rhipidoglossan radulae, used as rakes or brooms that brush and
collect loose marine debris. This type of radula is found in the giant keyhole
limpet (Megathura crenulata). The large size of this organism suggests that the
rhipidoglossan radula entails a technological superiority for M. crenulata in its
habitat. The structure and function of the radulae teeth have however not been
reported in detail. Using a combination of 2D and 3D microscopy techniques
coupled with amino acid analysis and X-ray scattering, we reveal the working
components of M. crenulata's radula. It is characterized by numerous marginal
teeth surrounding a pair of major hook-like lateral teeth, two pairs of minor
lateral teeth and a large central tooth. The mature major lateral teeth show
pronounced signs of wear, which gradually increase towards the very front end of
the radula and are evidence for scraping. An abrupt change in the amino acid
composition in the major lateral teeth and the concurrent formation of a
chitinous fiber-network mark the onset of tooth maturation. In comparison to the
simpler rock-scraping doccoglossate limpets, the radula of M. crenulata forms an
elaborate feeding apparatus, which can be seen as a natural harvest machine.
PMID- 26433030
TI - Molecular events during the early stages of aggregation of GNNQQNY: An all atom
MD simulation study of randomly dispersed peptides.
AB - This study probes the early events during lag phase of aggregation of GNNQQNY
using all atom MD simulations in explicit solvent. Simulations were performed by
varying system size, temperature and starting configuration. Peptides dispersed
randomly in the simulation box come together early on in the simulation and form
aggregates. These aggregates are dynamic implying the absence of stabilizing
interactions. This facilitates the exploration of alternate arrangements. The
constituent peptides sample a variety of conformations, frequently re-orient and
re-arrange with respect to each other and dissociate from/re-associate with the
aggregate. The size and lifetime of aggregates vary depending upon the number of
inter-peptide backbone H-bonds. Most of the aggregates formed are amorphous but
crystalline aggregates of smaller size (mainly 2-mers) do appear and sustain for
varying durations of time. The peptides in crystalline 2-mers are mostly anti
parallel. The largest crystalline aggregate that appears is a 4-mer in a single
sheet and a 4-, 5-, or 6-mer in double layered arrangement. Crystalline
aggregates grow either by the sequential addition of peptides, or by the head-on
or lateral collision-adhesion of 2-mers. The formation of various smaller
aggregates suggests the polymorphic nature of oligomers and heterogeneity in the
lag phase.
PMID- 26433031
TI - Structural and biochemical insights into the DNA-binding mode of MjSpt4p:Spt5
complex at the exit tunnel of RNAPII.
AB - Spt5 (NusG in bacteria) is the only RNA polymerase-associated factor known to be
conserved in all three domains of life. In archaea and eukaryotes, Spt5
associates with Spt4, an elongation factor that is absent in bacteria, to form a
functional heterodimeric complex. Previous studies suggest that the Spt4:Spt5
complex interacts directly with DNA at the double-stranded DNA exit tunnel of RNA
polymerase to regulate gene transcription. In this study, the DNA-binding ability
of Spt4:Spt5 from the archaeon Methanocaldococcus jannaschii was confirmed via
nuclear magnetic resonance chemical shift perturbation and fluorescence
polarization assays. Crystallographic analysis of the full-length MjSpt4:Spt5
revealed two distinct conformations of the C-terminal KOW domain of Spt5. A
similar alkaline region was found on the Spt4:Spt5 surface in both crystal forms,
and identified as double-stranded DNA binding patch through mutagenesis
fluorescence polarization assays. Based on these structural and biochemical data,
the Spt4:Spt5-DNA binding model was built for the first time.
PMID- 26433032
TI - Expression of the CD68 glycoprotein in the rat epididymis.
AB - The 110 kDa trans-membrane glycoprotein CD68 is highly expressed by human
monocytes and tissue macrophages. However, in addition to the monocyte/macrophage
system, CD68 has been also found in normal and tumor cells with no macrophagic
activity such as lymphocytes, fibroblasts, endothelial cells, small intestinal
epithelial cells, and neoplastic cells of different origins. Here, for the first
time we demonstrate the immunohistochemical localization of CD68 in the principal
cells of the cranial and caudal segments of rat epididymis. These results were
confirmed by biochemical analyses showing the expression of CD68 mRNA transcripts
and the protein in the epididymis tissues. Our findings, while providing further
evidence that CD68 expression is not restricted to the monocyte/macrophage
system, suggest that the glycoprotein might be involved in the functions of
epididymal principal cells that contribute to spermatozoa maturation process.
PMID- 26433034
TI - Cervical flexion myelopathy causing distal upper limb amyotrophy.
PMID- 26433033
TI - A conserved linkage group on chromosome 6, the 8.1 ancestral haplotype, is a
predisposing factor of chronic rhinosinusitis associated with nasal polyposis in
aspirin-sensitive Hungarians.
AB - Inflammation plays a central role in the pathogenesis of chronic rhinosinusitis
(CRS), and TNFalpha is a key pro-inflammatory cytokine in the pathogenesis of
this disease. In our previous studies, we showed that the TNFA -308A allele is a
genetic predisposition factor in a subgroup of aspirin-sensitive (ASA+) CRS
patients suffering from nasal polyps (NP) in the Hungarian population. To
determine whether the TNF -308A allele or the presence of a complex, extended
ancestral haplotype (8.1AH) located on chromosome 6 is responsible for the
previously observed genetic effect, we performed a case-control study for
examining the frequency of 8.1AH carriers in controls and in subgroups of CRS
patients. Our novel observations demonstrate that the presence of the 8.1AH may
be responsible for the development of severe forms of CRS (CRSwNP, ASA+) and
strengthen the clinical observation that CRS patients can be classified into
clinically and genetically different subgroups.
PMID- 26433035
TI - Spontaneous regression of a retro-odontoid cyst.
PMID- 26433036
TI - Congenital odontoid process separation with atlantoaxial dislocation associated
with Klipple-Feil syndrome and cervical angular kyphosis secondary to C6 wedging
vertebra.
PMID- 26433037
TI - Spinal cord injury enhances arterial expression and reactivity of alpha1
adrenergic receptors-mechanistic investigation into autonomic dysreflexia.
AB - BACKGROUND CONTEXT: Autonomic dysreflexia (AD) usually presents with a
significant increase in blood pressure, and uncontrollable autonomic response to
stimuli below the level of spinal cord injury (SCI). PURPOSE: This study analyzed
the vasomotor function and molecular changes in the peripheral arteries below the
lesion of SCI to characterize the mechanism of autonomic dysreflexia. STUDY
DESIGN: This was a randomized experimental study in rats. METHODS: Contusive SCI
was induced using a force-calibrated weight-drop device at the T10 level in
anesthetized rats. Two weeks after severe SCI, blood flow in the femoral arteries
was measured, and the vasomotor function and expression of alpha1-adrenergic
receptors were analyzed. RESULTS: Blood flow in the femoral artery was
significantly reduced in rats with SCI (8.0+/-2 vs. 17.5+/-4 mL/min, SCI vs.
control, respectively; p=.016). The contraction responses of femoral artery
segments to cumulative addition of alpha1-adrenergic agonist phenylephrine were
significantly enhanced in rats with SCI. Expression of alpha1-adrenergic receptor
was upregulated in the medial layer of femoral artery vascular homogenates of
these rats. CONCLUSION: Our study provides evidence demonstrating that prolonged
denervation below the lesion level following SCI results in a compensatory
increased expression of alpha1-adrenergic receptors in the arterial smooth muscle
layer, thereby enhancing the responsiveness to alpha1-adrenergic agonist and
potentiating the development of AD.
PMID- 26433038
TI - Development of a Rat Model of Mechanically Induced Tunable Pain and Associated
Temporomandibular Joint Responses.
AB - PURPOSE: Although mechanical overloading of the temporomandibular joint (TMJ) is
implicated in TMJ osteoarthritis (OA) and orofacial pain, most experimental
models of TMJ-OA induce only acute and resolving pain, which do not meaningfully
simulate the pathomechanisms of TMJ-OA in patients with chronic pain. The aim of
this study was to adapt an existing rat model of mechanically induced TMJ-OA, to
induce persistent orofacial pain by altering only the jaw-opening force, and to
measure the expression of common proxies of TMJ-OA, including degradation and
inflammatory proteins, in the joint. MATERIALS AND METHODS: TMJ-OA was
mechanically induced in a randomized, prospective study using 2 magnitudes of
opening loads in separate groups (ie.,. 2-N, 3.5-N and sham control [no load]).
Steady mouth opening was imposed daily (60 minutes/day for 7 days) in female
Holtzman rats, followed by 7 days of rest, and orofacial sensitivity was measured
throughout the loading and rest periods. Joint structure and extent of
degeneration were assessed at day 14 and expression of matrix metalloproteinase
13 (MMP-13), hypoxia-inducible factor-1alpha (HIF-1alpha), and tumor necrosis
factor-alpha (TNF-alpha) in articular cartilage was evaluated by
immunohistochemistry and quantitative densitometry methods at day 7 between the 2
loading and control groups. Statistical differences of orofacial sensitivity and
chondrocyte expression between loading groups were computed and significance was
set at a P value less than .05. RESULTS: Head-withdrawal thresholds for the 2
loading groups were significantly decreased during loading (P < .0001), but that
decrease remained through day 14 only for the 3.5-N group (P < .00001). At day
14, TMJs from the 2-N and 3.5-N groups exhibited truncation of the condylar
cartilage, typical of TMJ-OA. In addition, a 3.5-N loading force significantly
upregulated MMP-13 (P < .0074), with nearly a 2-fold increase in HIF-1alpha (P <
.001) and TNF-alpha (P < .0001) at day 7, in 3.5-N loaded joints over those
loaded by 2 N. CONCLUSION: Unlike a 2-N loading force, mechanical overloading of
the TMJ using a 3.5-N loading force induced constant and nonresolving pain and
the upregulation of inflammatory markers only in the 3.5-N group, suggesting that
these markers could predict the maintenance of persistent orofacial pain. As
such, the development of a tunable experimental TMJ-OA model that can separately
induce acute or persistent orofacial pain using similar approaches provides a
platform to better understand the pathomechanisms involved and possibly to
evaluate potential treatment strategies for patients with painful TMJ-OA.
PMID- 26433039
TI - Primary Intraosseous Squamous Cell Carcinoma of the Jaws: 6 New Cases,
Experience, and Literature Comparison.
AB - PURPOSE: To analyze the clinical, histologic, radiologic, therapeutic, and
prognostic aspects of 6 cases of an uncommon head and neck malignancy and compare
these results with data in the literature. MATERIALS AND METHODS: The medical
histories of all patients treated in the Maxillofacial Surgery Unit in San
Gerardo Hospital (Monza, Italy) for primitive intraosseous squamous cell
carcinoma (PIOSCC) of the jaw were reviewed. All patients were considered
suitable for inclusion in the study, specifically those whose oral mucosa had not
been compromised and who did not have distant metastases. RESULTS: Six patients
were included (4 male, 2 female). The odontogenic origin was histologically shown
in only 2 patients. The male-to-female ratio was 2:1, and the malignancy occurred
in the posterior mandible in 50% of cases. The most common symptoms were swelling
and pain, but no sensory disturbances were observed. Radiologic findings
indicated considerable variation in presentation, including small cystic lesions,
which might complicate a pathologic diagnosis. All patients in the study were
treated with surgery, and 2 patients received adjuvant radiotherapy. Cervical
node metastases were present in 33% of patients. All patients are currently alive
and free of disease. CONCLUSION: PIOSCC is a rare malignancy of the head and
neck. Diagnosis can be difficult during the early stages of disease owing to a
lack of clinical symptoms or radiologic presentation. Treatment is surgical and,
like every other cancer, must be adequate to cure the cancer.
PMID- 26433040
TI - Effects of a Single-Dose of Pre-Emptive Pregabalin on Postoperative Pain and
Opioid Consumption After Double-Jaw Surgery: A Randomized Controlled Trial.
AB - PURPOSE: The effect of a single-dose of pre-emptive pregabalin is still unknown,
although it is used as an adjuvant in controlling acute postoperative pain. The
purpose of this study was to evaluate the effects of pre-emptive single-dose
pregabalin on postoperative acute pain and 24-hour opioid consumption in patients
who underwent double-jaw surgery. PATIENTS AND METHODS: Forty patients (18 to 45
yr old; American Society of Anesthesiologists status I to II) for whom elective
double-jaw surgery was planned under general anesthesia were included in this
study, which had been planned as a prospective, randomized, and double-blinded
study. Patients were randomly divided into 2 groups: the pregabalin group (n =
20) was given pregabalin 150 mg orally 1 hour before general anesthesia and the
placebo group (n = 20) was given an oral placebo capsule. The groups were
administered the routine general anesthesia protocol. Postoperative analgesia was
performed intravenously in the 2 groups twice a day with dexketoprofen trometamol
50 mg and patient-controlled analgesia with fentanyl. Postoperative analgesia was
evaluated using the visual analog scale (VAS). Fentanyl consumption, additional
analgesia requirement, and side-effects were recorded during the first 24 hours
after surgery. Descriptive and bivariate statistics were computed, and
significance was set at a P value less than .05. RESULTS: Compared with placebo,
the VAS score was statistically lower in the pregabalin group during the early
postoperative period (P < .05). The 24-hour opioid consumption was significantly
higher in the placebo group compared with the pregabalin group (509.40 +/- 261.56
vs. 260.10 +/- 246.53 MUq, respectively; P = .004). In addition, the analgesia
requirement was statistically lower in the pregabalin group (P < .05). Nausea or
vomiting was observed more often in the placebo group, whereas other side-effects
were similar for the 2 groups. CONCLUSION: A single 150-mg dose of pre-emptive
pregabalin decreased postoperative opioid consumption in the first 24 hours after
double-jaw surgery. Multimodal analgesia techniques that contain pre-emptive
analgesia can be used successfully in preventing postoperative pain caused by
orthognathic surgery.
PMID- 26433041
TI - Adipose-Derived Stem Cells Decrease Bone Morphogenetic Protein Type 2-Induced
Inflammation In Vivo.
AB - PURPOSE: Recombinant human bone morphogenetic protein type 2 (rhBMP-2) has been
used to promote bone regeneration. In contrast, some reports have suggested rhBMP
2 does not provide advantages over autogenous bone grafting owing to the
undesirable postoperative symptoms of this growth factor. Because the undesirable
symptoms of rhBMP-2 are usually promoted by inflammation, this study evaluated
the in vivo effect of human adipose-derived stem cells (ASCs) incorporated into
polylactic co-glycolic acid (PLGA) scaffolds in decreasing the inflammatory
response induced by a low dose of rhBMP-2. MATERIALS AND METHODS: PLGA scaffolds
were characterized and loaded with rhBMP-2 1, 2.5, or 5 MUg per scaffold (n = 6)
and the in vitro released protein amounts were quantified at 7 hours and 1, 7,
and 21 days after loading (n = 3). The muscle tissue of 6 beagles received the
following treatments: PLGA, PLGA plus rhBMP-2 (2.5 MUg), and PLGA plus rhBMP-2
plus ASCs (1 * 10(6) ASCs). The samples were evaluated 45 days after surgery.
Statistical analyses were performed and the P value was set at .05. RESULTS: PLGA
plus rhBMP-2 plus ASCs yielded the smallest number of inflammatory foci (P <
.001) and giant cells (P < .001) and the largest number of angiogenesis sites (P
< .001). CONCLUSIONS: Human ASCs administered in vivo into PLGA scaffolds with a
low dose of rhBMP-2 decrease tissue inflammation and increase angiogenesis in
muscular sites.
PMID- 26433042
TI - Epidural Tube: A Useful Device in Sialendoscopy Operations.
AB - Salivary endoscopy, which was first described in 1991, is a safe technique with
few complications. The sialendoscopy operation has been developed and
successfully offered as a minimally invasive and gland-preserving approach for
the treatment of chronic obstructive sialadenitis. For many surgeons, entering
the duct lumen of the salivary gland is the most difficult and time-consuming
step of the sialendoscopy operation. This report introduces a timesaving and
straightforward method for entering the duct lumen using an epidural tube, which
is a plastic tube with a blunt tip.
PMID- 26433043
TI - Alterations in hippocampal myelin and oligodendrocyte precursor cells during
epileptogenesis.
AB - Recent reports have described damage to myelinated fibers in the central nervous
system (CNS) in patients with temporal lobe epilepsy (TLE) and animal models.
However, only limited data are available on the dynamic changes that occur in
myelinated fibers, oligodendrocytes (which are myelin-forming cells), and
oligodendrocyte precursor cells (OPCs), which are a reservoir of new
oligodendrocytes, in the hippocampus throughout epileptogenesis. The current
study was designed to examine this issue using a rat model of lithium-pilocarpine
induced epilepsy. Electroencephalography (EEG), immunofluorescence, and Western
blot analysis showed that the loss of myelin and oligodendrocytes in the rat
hippocampus began during the acute stage of epileptogenesis, and the severity of
this loss increased throughout epileptogenesis. Accompanying this loss of myelin
and oligodendrocytes, OPCs in the rat hippocampus became activated and their
populations increased during several phases of epileptogenesis (the acute, latent
and chronic phases). The transcription factors olig1 and olig2, which play
crucial roles in regulating OPC proliferation, differentiation and remyelination,
were up-regulated during the early phases (the acute and latent phases) followed
by a sharp decline in their expression during the chronic and late chronic
phases. This study is the first to confirm the loss of myelin and
oligodendrocytes during lithium-pilocarpine-induced epileptogenesis accompanied
by a transient increase in the number of OPCs. Prevention of the loss of myelin
and oligodendrocytes may provide a novel treatment strategy for epilepsy.
PMID- 26433045
TI - At the Intersection of Poverty and Disability: Supplemental Security Income for
Children With Disabilities Due to Mental Health Problems.
PMID- 26433044
TI - The effects of repetitive vibration on sensorineural function: biomarkers of
sensorineural injury in an animal model of metabolic syndrome.
AB - Exposure to hand-transmitted vibration in the work-place can result in the loss
of sensation and pain in workers. These effects may be exacerbated by pre
existing conditions such as diabetes or the presence of primary Raynaud's
phenomena. The goal of these studies was to use an established model of vibration
induced injury in Zucker rats. Lean Zucker rats have a normal metabolic profile,
while obese Zucker rats display symptoms of metabolic disorder or Type II
diabetes. This study examined the effects of vibration in obese and lean rats.
Zucker rats were exposed to 4h of vibration for 10 consecutive days at a
frequency of 125 Hz and acceleration of 49 m/s(2) for 10 consecutive days.
Sensory function was checked using transcutaneous electrical stimulation on days
1, 5 and 9 of the exposure. Once the study was complete the ventral tail nerves,
dorsal root ganglia and spinal cord were dissected, and levels of various
transcripts involved in sensorineural dysfunction were measured. Sensorineural
dysfunction was assessed using transcutaneous electrical stimulation. Obese
Zucker rats displayed very few changes in sensorineural function. However they
did display significant changes in transcript levels for factors involved in
synapse formation, peripheral nerve remodeling, and inflammation. The changes in
transcript levels suggested that obese Zucker rats had some level of sensory
nerve injury prior to exposure, and that exposure to vibration activated pathways
involved in injury and re-innervation.
PMID- 26433046
TI - Impact of Wheelchair Rugby on Body Composition of Subjects With Tetraplegia: A
Pilot Study.
AB - OBJECTIVE: To investigate the longitudinal effects of wheelchair rugby (WR)
training on body composition of subjects with tetraplegia. DESIGN: Subjects were
evaluated at baseline and after WR training. SETTING: Faculty of physical
education settings. PARTICIPANTS: Individuals with tetraplegia (N=13; age, 26.6+/
6.0y). INTERVENTIONS: Four sessions per week of WR training composed by aerobic
and anaerobic activities and technical and tactical aspects of WR. The average
time of intervention was 8.1+/-2.5 months. MAIN OUTCOME MEASURES: Body
composition assessed by dual-energy x-ray absorptiometry. RESULTS: After
training, fat mass was significantly reduced in the whole body (15,191+/-4603 vs
13,212+/-3318 g, P=.016), trunk (7058+/-2639 vs 5693+/-1498 g, P=.012), and legs
(2847+/-817 vs 2534+/-742 g, P=.003). Conversely, increased bone mineral content
(183+/-35 vs 195+/-32 g, P=.01) and fat-free mass (2991+/-549 vs 3332+/-602 g,
P=.016) in the arms and reduced bone mineral content in the trunk (553+/-82 vs
521+/-86 g, P=.034) were observed after training. Furthermore, no significant
correlation between the duration of training and changes in body composition was
detected. CONCLUSIONS: Regular WR training increased lean mass and bone mineral
content in the arms and decreased total body fat mass. Conversely, WR training
was associated with decreased bone mineral content in the trunk. These results
suggest that regular WR training improves body composition in subjects with
tetraplegia.
PMID- 26433047
TI - Nanobody-functionalized PEG-b-PCL polymersomes and their targeting study.
AB - We prepared and characterized polymersomes functionalized with nanobodies (VHHs)
on the basis of biocompatible, biodegradable and FDA-approved poly(ethylene
glycol)-block-poly(epsilon-caprolactone) (PEG-b-PCL). Fluorescein isothiocyanate
(FITC) and N-beta-maleimidopropyl-oxysuccinimide ester were allowed reacting with
H2N-PEG-b-PCL to produce FITC and maleimide (Mal) functionalized copolymers, Mal
PEG-b-PCL and FITC-PEG-b-PCL. A mixture of MeO-PEG-b-PCL, Mal-PEG-b-PCL and FITC
PEG-b-PCL was used to prepare polymersomes by thin film hydration and
nanoprecipitation methods. Morphological studies by cryogenic transmission
electron microscopy (Cryo-TEM) showed that the nanoparticles exhibited
predominantly vesicular structures (polymersomes). Their mean diameters measured
by dynamic light scattering were around 150 nm and the zeta-potentials around -1
mV at pH 7.4. The nanoparticles were functionalized with either anti-HER2 (VHH1)
or anti-GFP (VHH2) nanobodies using maleimide-cysteine chemistry. Their particle
size and zeta-potential increased slightly after nanobody-functionalization. The
specific binding of VHH-functionalized polymersomes and control nanoparticles
towards HER2 positive breast cancer cells was analyzed by flow cytometry and
confocal microscopy. The collected results represent the first report which
experimentally demonstrates that VHH1-functionalized PEO-b-PCL polymersomes can
target specifically breast cancer cells expressing HER2 receptors. The detailed
morphological and cell-binding studies described herein pave the way for future
in vivo studies to evaluate the feasibility to use such nanoparticles for
targeted drug delivery.
PMID- 26433049
TI - Budget constrained non-monotonic feature selection.
AB - Feature selection is an important problem in machine learning and data mining. We
consider the problem of selecting features under the budget constraint on the
feature subset size. Traditional feature selection methods suffer from the
"monotonic" property. That is, if a feature is selected when the number of
specified features is set, it will always be chosen when the number of specified
feature is larger than the previous setting. This sacrifices the effectiveness of
the non-monotonic feature selection methods. Hence, in this paper, we develop an
algorithm for non-monotonic feature selection that approximates the related
combinatorial optimization problem by a Multiple Kernel Learning (MKL) problem.
We justify the performance guarantee for the derived solution when compared to
the global optimal solution for the related combinatorial optimization problem.
Finally, we conduct a series of empirical evaluation on both synthetic and real
world benchmark datasets for the classification and regression tasks to
demonstrate the promising performance of the proposed framework compared with the
baseline feature selection approaches.
PMID- 26433048
TI - Total synthesis of biologically active 20S-hydroxyvitamin D3.
AB - A total synthetic strategy of 20S-hydroxyvitamin D3 [20S-(OH)D3] involving
modified synthesis of key intermediates 7 and 12, Grignard reaction to
stereoselectively generate 20S-OH and Wittig-Horner coupling to establish D3
framework, was completed in 16 steps with an overall yield of 0.4%. The synthetic
20S-(OH)D3 activated vitamin D receptor (VDR) and initiated the expression of
downstream genes. In addition, 20S-(OH)D3 showed similar inhibitory potency as
calcitriol [1,25(OH)2D3] on proliferation of melanoma cells.
PMID- 26433050
TI - Binding of inferred germline precursors of broadly neutralizing HIV-1 antibodies
to native-like envelope trimers.
AB - HIV-1 envelope glycoproteins (Env) and Env-based immunogens usually do not
interact efficiently with the inferred germline precursors of known broadly
neutralizing antibodies (bNAbs). This deficiency may be one reason why Env and
Env-based immunogens are not efficient at inducing bNAbs. We evaluated the
binding of 15 inferred germline precursors of bNAbs directed to different epitope
clusters to three soluble native-like SOSIP.664 Env trimers. We found that native
like SOSIP.664 trimers bind to some inferred germline precursors of bNAbs,
particularly ones involving the V1/V2 loops at the apex of the trimer. The data
imply that native-like SOSIP.664 trimers will be an appropriate platform for
structure-guided design improvements intended to create immunogens able to target
the germline precursors of bNAbs.
PMID- 26433051
TI - Addition of N-glycosylation sites on the globular head of the H5 hemagglutinin
induces the escape of highly pathogenic avian influenza A H5N1 viruses from
vaccine-induced immunity.
AB - Highly pathogenic avian influenza A H5N1 viruses remain endemic in poultry in
several countries and still constitute a pandemic threat. Since the early 20th
century, we experienced four influenza A pandemics. H3N2 and H1N1pdm09 viruses
that respectively emerged during 1968 and 2009 pandemics are still responsible
for seasonal epidemics. These viruses evolve regularly by substitutions in
antigenic sites of the hemagglutinin (HA), which prevent neutralization by
antibodies directed against previous strains (antigenic drift). For seasonal H3N2
viruses, an addition of N-glycosylation sites (glycosites) on H3 contributed to
this drift. Here, we questioned whether additional glycosites on H5 could induce
an escape of H5N1 virus from neutralization, as it was observed for seasonal H3N2
viruses. Seven H5N1 mutants were produced by adding glycosites on H5. The most
glycosylated virus escaped from neutralizing antibodies, in vitro and in vivo.
Furthermore, a single additional glycosite was responsible for this escape.
PMID- 26433052
TI - Blind people are more sensitive than sighted people to binaural sound-location
cues, particularly inter-aural level differences.
AB - Blind people use auditory information to locate sound sources and sound
reflecting objects (echolocation). Sound source localization benefits from the
hearing system's ability to suppress distracting sound reflections, whereas
echolocation would benefit from "unsuppressing" these reflections. To clarify how
these potentially conflicting aspects of spatial hearing interact in blind versus
sighted listeners, we measured discrimination thresholds for two binaural
location cues: inter-aural level differences (ILDs) and inter-aural time
differences (ITDs). The ILDs or ITDs were present in single clicks, in the
leading component of click pairs, or in the lagging component of click pairs,
exploiting processes related to both sound source localization and echolocation.
We tested 23 blind (mean age = 54 y), 23 sighted-age-matched (mean age = 54 y),
and 42 sighted-young (mean age = 26 y) listeners. The results suggested greater
ILD sensitivity for blind than for sighted listeners. The blind group's
superiority was particularly evident for ILD-lag-click discrimination, suggesting
not only enhanced ILD sensitivity in general but also increased ability to
unsuppress lagging clicks. This may be related to the blind person's experience
of localizing reflected sounds, for which ILDs may be more efficient than ITDs.
On the ITD-discrimination tasks, the blind listeners performed better than the
sighted age-matched listeners, but not better than the sighted young listeners.
ITD sensitivity declines with age, and the equal performance of the blind
listeners compared to a group of substantially younger listeners is consistent
with the notion that blind people's experience may offset age-related decline in
ITD sensitivity.
PMID- 26433053
TI - Cochlear implantation as a long-term treatment for ipsilateral incapacitating
tinnitus in subjects with unilateral hearing loss up to 10 years.
AB - INTRODUCTION: The authors previously demonstrated that tinnitus resulting from
unilateral hearing loss (UHL) can be treated with electrical stimulation via a
Cochlear Implant (CI). The study aimed to do a long-term (LT) evaluation of CI in
subjects suffering from UHL and accompanied incapacitating tinnitus up to 10
years. The primary focus of the study is on LT tinnitus reduction. SUBJECTS: LT
evaluation was derived from 23 subjects suffering from UHL and accompanied
incapacitating tinnitus (Pre-operative Tinnitus Loudness Visual Analogue Scale
(VAS) score >6/10). They were cochlear implanted at a median age of 55 years (22
71 yr) and had 8 years (3-10 yr) experience with their CI at the LT testing. The
subjects were categorized into two groups: a Single-Sided Deaf Group (SSD) and an
Asymmetric Hearing Loss Group (AHL). The SSD group comprises subjects with
contralateral normal hearing (i.e. air conduction pure tone average (PTA0.5, 1, 2
and 4 kHz) <= 30 dB HL) and the AHL group subjects with contralateral mild to
moderate hearing loss (i.e. air conduction PTA0.5, 1, 2 and 4 kHz > 30 dB HL).
METHODS: In order to obtain a LT structural overview of the CI use in UHL
subjects, a structured interview was conducted including questions about daily
amount of CI use, residual inhibition of the tinnitus after switch off, tinnitus
type, etc. The VAStinnitus loudness and the Tinnitus Questionnaire were obtained
pre-operatively, one, three, six, 12, and 36-months post-operatively and at the
long-term test interval (8 (3-10 years) post-operative). The Hyperacusis
Questionnaire was administered in the CION and the CIOFF condition. RESULTS: The
structural interview revealed that all patients (23/23) still wear their CI seven
days a week, eight (3-10) years after cochlear implantation. It appeared that in
all subjects but one CI switch-on is the first act when rising and CI switch-off
is the last act before bedtime. In the SSD group, tinnitus suppression is still
the primary benefit reported (83%), whereas in the AHL the majority of the
subjects (55%) report that the primary benefit shifted to improved hearing. In
the majority of the subjects the tinnitus reduction starts within 1 min (in 70%
of the cases) and the residual inhibition after CI switch-off is less than a
minute (in 65% of the cases). The VAS and TQ scores significantly improved up to
three months after the first-fitting and remain stable up to the LT test
interval. The median score on the Hyperacusis Questionnaire was 17 (7-36) in the
CIOFF condition and improved to 23,5 (12-39) in the CION condition in the SSD
group. CONCLUSION: This is the first study to report on LT results in a large
number of UHL CI users, up to 10 years. Structured interviews shows that 100% of
the subjects wears their CI seven days a week. The tinnitus reduces significantly
up to three months after the first-fitting and the tinnitus reduction remain
stable up to the LT test interval. The SSD group report tinnitus reduction as the
primary benefit, whereas the majority of the AHL group report improved hearing as
the primary benefit, eight (3-10) years after implantation. In addition to the
tinnitus reduction, the CI provides also a benefit regarding reported.
PMID- 26433054
TI - Cannabinoids, cannabinoid receptors and tinnitus.
AB - One hypothesis suggests that tinnitus is a form of sensory epilepsy, arising
partly from neuronal hyperactivity in auditory regions of the brain such as the
cochlear nucleus and inferior colliculus. Although there is currently no
effective drug treatment for tinnitus, anti-epileptic drugs are used in some
cases as a potential treatment option. There is increasing evidence to suggest
that cannabinoid drugs, i.e. cannabinoid receptor agonists, can also have anti
epileptic effects, at least in some cases and in some parts of the brain. It has
been reported that cannabinoid CB1 receptors and the endogenous cannabinoid, 2
arachidonylglycerol (2-AG), are expressed in the cochlear nucleus and that they
are involved in the regulation of plasticity. This review explores the question
of whether cannabinoid receptor agonists are likely to be pro- or anti-epileptic
in the cochlear nucleus and therefore whether cannabinoids and Cannabis itself
are likely to make tinnitus better or worse.
PMID- 26433055
TI - PDCD5 functions as a regulator of p53 dynamics in the DNA damage response.
AB - The tumor suppressor p53 plays a central role in cell fate decisions after DNA
damage. Programmed Cell Death 5 (PDCD5) interacts with the p53 pathway to promote
cell apoptosis. Recombinant human PDCD5 can significantly sensitize different
cancers to chemotherapies. In the present paper, we construct a computational
model that includes PDCD5 interactions in the p53 signaling network and study the
effects of PDCD5 on p53-mediated cell fate decisions during the DNA damage
response. Our results revealed that PDCD5 functions as a co-activator of p53 and
regulates p53-dependent cell fate decisions via the mediation of p53 dynamics.
The effects of PDCD5 are dose-dependent, such that p53 activity exhibits
sustained low level, pulsed oscillations, or sustained high level dynamics
depending on the PDCD5 level following DNA damage. Moreover, PDCD5 regulates
caspase-3 activation via two mechanisms during the two phases of sustained and
pulsed p53 dynamics. This study provides insights regarding how PDCD5 functions
as a regulator of the p53 pathway and might be helpful for increasing our
understanding of the molecular mechanisms by which PDCD5 can be used to treat
cancers.
PMID- 26433056
TI - Redox modulation of cellular stress response and lipoxin A4 expression by
Coriolus versicolor in rat brain: Relevance to Alzheimer's disease pathogenesis.
AB - Increasing evidence supports the notion that oxidative stress-driven
neuroinflammation is an early pathological feature in neurodegenerative diseases.
As a prominent intracellular redox system involved in neuroprotection, the
vitagene system is emerging as a potential neurohormetic target for novel
cytoprotective interventions. Vitagenes encode for cytoprotective heat shock
proteins 70, heme oxygenase-1, thioredoxin and lipoxin A4. Emerging interest is
now focusing on molecules capable of activating the vitagene system as novel
therapeutic targets to minimize deleterious consequences associated with free
radical-induced cell damage, such as in neurodegeneration. Mushroom-derived
lipoxin A4 (LXA4) is an emerging endogenous eicosanoid able to promote resolution
of inflammation, acting as an endogenous "braking signal" in the inflammatory
process. Mushrooms have long been used in traditional medicine for thousands of
years, being now increasingly recognized as rich source of polysaccharopeptides
endowed with significant antitumor, antioxidant, antiviral, antibacterial and
cytoprotective effects, thereby capable of stimulating host immune responses.
Here we provide evidence of a neuroprotective action of the Coriolus mushroom
when administered orally to rat. Expression of LXA4 was measured in different
brain regions after oral administration of a Coriolus biomass preparation, given
for 30 days. LXA4 up-regulation was associated with an increased content of redox
sensitive proteins involved in cellular stress response, such as Hsp72, heme
oxygenase-1 and thioredoxin. In the brain of rats receiving Coriolus, maximum
induction of LXA4 was observed in cortex and hippocampus. Hsps induction was
associated with no significant changes in IkBalpha, NFkB and COX-2 brain levels.
Conceivably, activation of LXA4 signaling and modulation of stress-responsive
vitagene proteins could serve as a potential therapeutic target for AD-related
inflammation and neurodegenerative damage.
PMID- 26433057
TI - Expression and function of toll-like receptors in human circulating endothelial
colony forming cells.
AB - Mature endothelial cells are known to sense microbial products through toll-like
receptors (TLRs), a family of membrane proteins which serve as pathogen
recognition and signaling elements; however, there are limited data in the
literature about the expression and function of TLRs in human circulating
endothelial colony forming cells (ECFCs), which are considered the most likely
endothelial precursors. We expanded and differentiated in vitro umbilical cord
blood (UCB) and adult peripheral blood (PB) ECFCs and studied the expression of
TLR1 to TLR10 mRNA by qPCR analysis, and we further characterized TLR function in
ECFCs through functional assays including in vitro ECFC growth and
differentiation, assessment of cytokine production, and measurement of
intracellular Ca(2+) signals. Both UCB- and PB-ECFCs had detectable mRNA levels
of all the TLRs from 1 to 10; TLR4, a sensor of Gram-negative bacterial
lipopolysaccharide (LPS), had a higher level compared to other TLRs. Exposure to
LPS induced cytokine production, although with less efficiency compared to PB
mononuclear cells. However, no effect of LPS was seen on ECFC growth and
differentiation, and no increase in intracellular Ca(2+) concentrations, which is
essential for ECFC proliferation, was observed after exposure to increasing
amounts of LPS. Our data show that all TLRs from 1 to 10 are constitutively
expressed in ECFCs, and suggest that TLR4 is functional in ECFCs, but its
activation through its ligand LPS does not affect ECFC growth and
differentiation.
PMID- 26433058
TI - Characteristics of the peripheral T cell immune response of patients at different
stages of vascular cognitive impairment.
AB - AIM: To investigate the characteristics of the peripheral T cell immune response
of patients at different stages of vascular cognitive impairment (VCI). METHODS:
61 Arterial atherosclerotic cerebral infarct induced VCI patients, including 28
vascular dementia (VaD) cases, 33 no dementia (VCI-ND) cases, and 25
atherosclerotic cerebral infarct patients with normal cognitive function (CI-NC)
as controls were enrolled. Peripheral CD8(+)T, CD4(+)CD25(+) Treg, CD4(+)IL-17(+)
Th17 cells proportion, and IL-1beta, IL-2, IL-6, IFN-gamma levels, and
neuropsychological function were assessed. RESULTS: There was no difference in
average age, gender ratio, years of education, and risk factors of infarct among
the three groups. Peripheral CD4(+)CD25(+) Treg in VCI-ND and VaD groups were
significantly lower than that in controls, and CD8(+) T cells were markedly
elevated in VaD group. The IL-17(+) Th17 cell proportion did not differ
significantly among three groups. IL-6 and IFN-gamma expression levels in VaD
group were higher than those in other two groups. The VDAS-Cog executive function
subscale score was negatively correlated with CD4(+)CD25(+) Treg proportion in
VCI patients, and positively correlated with IL-6 levels. CONCLUSION: VCI
patients demonstrated a decrease in peripheral CD4(+) Treg proportion and
increased IL-6 expression, and both parameters were correlated with the decline
of executive functions.
PMID- 26433059
TI - Antibody profile in Indian severe haemophilia A patients with and without FVIII
inhibitors.
AB - Diagnosis and management of haemophilia patients with inhibitors is often tricky
due to the heterogeneous nature of the antibodies with regard to their kinetics,
as well as the co-existence of other interfering antibodies. Plasma samples from
severe haemophilia A patients from India with and without FVIII inhibitors were
analysed for the presence of possible co-existing antibodies such as lupus
anticoagulants (LA), anti-cardiolipin antibodies (ACLA), anti-beta2-glycoprotein
I (anti-beta2-GP-I) antibodies, viral transfusion transmitted disease (HIV,
HBsAg, HCV) related antibodies, anti-cyclic citrullinated peptides (anti-CCP),
and anti-nuclear antibodies. A high incidence of LA and anti-HCV antibodies was
detected in Indian haemophilia A patients similar to earlier reports. More
importantly, a relatively high incidence of autoantibodies to nuclear antigens
(18.62%) and anti-CCP antibodies (1.38%) associated with autoimmune disorders was
also seen in these congenital haemophilia A patients with and without inhibitors.
Knowledge on the antibody profile in these haemophilia patients especially in
those with FVIII inhibitors along with correlation with the clinical
manifestations and other risk factors for inhibitor development could possibly
shed more light on the complex immune response in these patients.
PMID- 26433060
TI - Glucocorticoid receptor exhibits sexually dimorphic expression in the medaka
brain.
AB - The differential impact of stress on brain functions of males and females has
been widely observed in vertebrates. Recent evidence suggests that stress-induced
glucocorticoid signaling affects sexual differentiation and sex changes in
teleost fish. These facts led us to postulate that there were sex differences in
glucocorticoid signaling in the teleost brain that underlie some sex differences
in their physiological and behavioral traits. Here we found sexually dimorphic
expression of a glucocorticoid receptor gene (gr1) in the brain of medaka fish
(Oryzias latipes), with females having greater expression in several preoptic and
thalamic nuclei. Further, gr1 exhibits female-biased expression in neurons of the
anterior parvocellular preoptic nucleus that produce the neuropeptides vasotocin
and gonadotropin-releasing hormone 1 (these neuropeptides have been implicated in
the regulation of neuroendocrine and behavioral functions). These findings
suggest that glucocorticoids have a greater influence on physiology and behavior
mediated by these neuropeptides in females than in males, which may contribute to
sex differences in the brain's response to stress.
PMID- 26433061
TI - Shaking the myth: Body mass, aggression, steroid hormones, and social dominance
in wild house mouse.
AB - In social mammals, the position of a male in the group's hierarchy strongly
affects his reproductive success. Since a high social rank is often gained
through competition with other males, selection should favour bigger males over
smaller ones. We may therefore predict faster growth and/or delayed sexual
maturity in dominant males. Likewise, dominants should have higher levels of
testosterone, hormone important in many aspects of male dominance. Less obvious
is the relationship between dominance and levels of corticosterone but generally
higher concentrations are expected in subordinate individuals. We studied body
growth, sexual maturation and endocrinal changes in males of two house mouse
subspecies, raised in fraternal pairs. Since Mus musculus domesticus is the
subspecies which dominates mutual encounters with Mus musculus musculus we
predicted higher growth rate, delayed puberty and aggression, and higher
testosterone and corticosterone levels in domesticus males compared to musculus.
In all comparisons, no differences were found between dominant and subordinate
musculus brothers. On the other hand, in M. m. domesticus, dominant males
revealed a different growth trajectory and lower corticosterone levels than
subordinate males but not delayed puberty and higher testosterone concentrations,
thus contradicting our predictions. In inter-subspecific comparisons, musculus
males matured earlier but became aggressive at the same time as domesticus males.
The musculus testosterone ontogeny suggests that social positions in this
subspecies remain unfixed for an extended period and that the increasing levels
probably reflect prolonged hierarchy contests. It appears that the ontogeny of
behaviour and physiological traits diverge cryptically between the two
subspecies.
PMID- 26433062
TI - Preventing Thrombosis to Improve Outcomes in Heart Failure Patients.
AB - Heart failure (HF) is associated with an increased risk of thrombotic events,
particularly if this condition is accompanied by atrial fibrillation (AF). Many
HF patients have background coronary artery disease (CAD) making them prone to
coronary thrombosis resulting in myocardial infarction or sudden death. Oral
anticoagulation is essential in the vast majority of HF patients with AF with non
vitamin K based anticoagulants being a suitable alternative to warfarin. In
contrast, aspirin alone does not provide adequate stroke prevention in such
patients. In HF without AF, oral anticoagulation should not be routinely used,
and antiplatelet agents should be prescribed in patients with background CAD.
This review provides an overview of prothrombotic factors and antithrombotic
management of patients with HF.
PMID- 26433063
TI - Loss of the Drosophila melanogaster DEAD box protein Ddx1 leads to reduced size
and aberrant gametogenesis.
AB - Mammalian DDX1 has been implicated in RNA trafficking, DNA double-strand break
repair and RNA processing; however, little is known about its role during animal
development. Here, we report phenotypes associated with a null Ddx1 (Ddx1(AX))
mutation generated in Drosophila melanogaster. Ddx1 null flies are viable but
significantly smaller than control and Ddx1 heterozygous flies. Female Ddx1 null
flies have reduced fertility with egg chambers undergoing autophagy, whereas
males are sterile due to disrupted spermatogenesis. Comparative RNA sequencing of
control and Ddx1 null third instars identified several transcripts affected by
Ddx1 inactivation. One of these, Sirup mRNA, was previously shown to be
overexpressed under starvation conditions and implicated in mitochondrial
function. We demonstrate that Sirup is a direct binding target of Ddx1 and that
Sirup mRNA is differentially spliced in the presence or absence of Ddx1.
Combining Ddx1 null mutation with Sirup dsRNA-mediated knock-down causes
epistatic lethality not observed in either single mutant. Our data suggest a role
for Drosophila Ddx1 in stress-induced regulation of splicing.
PMID- 26433065
TI - A photoelectrochemical biosensor for fibroblast-like synoviocyte cell using
visible light-activated NCQDs sensitized-ZnO/CH3NH3PbI3 heterojunction.
AB - Based on ZnO nanorods (NRs)/CH3NH3PbI3/nitrogen-doped carbon quantum dots (NCQDs)
nanocomposites, the highly sensitive detection of fibroblast-like synoviocyte
(FLS) cell was realized by a photoelectrochemical (PEC) biosensor.
ZnO/CH3NH3PbI3/NCQDs nanocomposites were exploited as the photo-to-electron
generator to produce the signal. CH3NH3PbI3 was spin-coated on ZnO surface after
ZnO NRs grew on ITO electrode then by dropping on the modified electrode, NCQDs
were diffused and adhered to the surface of ZnO and CH3NH3PbI3. In the presence
of EDC/NHS, the combination of CH3NH3PbI3 and NCQDs was achieved by the carboxyl
groups (-COOH) and amino groups (-NH2) in the preparation process. Furthermore,
the capture probe of FLS cell, CD95 antibody, can be anchored by -COOH and -NH2
groups through EDC/NHS. The specific recognition between the antibody capture
probes and cell targets gained high-sensitive detection for FLS cell for the
first time. The developed biosensor showed a wide linear range from 1.0 *
10(4)cell/mL to 10 cell/mL and a low detection limit of 2 cell/mL. This kind of
biosensor would provide a novel detection strategy for FLS cell.
PMID- 26433064
TI - RNA sequences required for the noncoding function of oskar RNA also mediate
regulation of Oskar protein expression by Bicoid Stability Factor.
AB - The Drosophila oskar (osk) mRNA is unusual in having both coding and noncoding
functions. As an mRNA, osk encodes a protein which is deployed specifically at
the posterior of the oocyte. This spatially-restricted deployment relies on a
program of mRNA localization and both repression and activation of translation,
all dependent on regulatory elements located primarily in the 3' untranslated
region (UTR) of the mRNA. The 3' UTR also mediates the noncoding function of osk,
which is essential for progression through oogenesis. Mutations which most
strongly disrupt the noncoding function are positioned in a short region (the C
region) near the 3' end of the mRNA, in close proximity to elements required for
activation of translation. We show that Bicoid Stability Factor (BSF) binds
specifically to the C region of the mRNA. Both knockdown of bsf and mutation of
BSF binding sites in osk mRNA have the same consequences: Osk expression is
largely eliminated late in oogenesis, with both mRNA localization and translation
disrupted. Although the C region of the osk 3' UTR is required for the noncoding
function, BSF binding does not appear to be essential for that function.
PMID- 26433066
TI - Ultrasensitive photoelectrochemical immunoassay for CA19-9 detection based on
CdSe@ZnS quantum dots sensitized TiO2NWs/Au hybrid structure amplified by
quenching effect of Ab2@V(2+) conjugates.
AB - A novel, enhanced photoelectrochemical immunoassay was established for sensitive
and specific detection of carbohydrate antigen 19-9 (CA19-9, Ag). In this
protocol, TiO2 nanowires (TiO2NWs) were first decorated with Au nanoparticles to
form TiO2NWs/Au hybrid structure, and then coated with CdSe@ZnS quantum dots
(QDs) via the layer-by-layer method, producing TiO2NWs/Au/CdSe@ZnS sensitized
structure, which was employed as the photoelectrochemical matrix to immobilize
capture CA19-9 antibodies (Ab1); whereas, bipyridinium (V(2+)) molecules were
labeled on signal CA19-9 antibodies (Ab2) to form Ab2@V(2+) conjugates, which
were used as signal amplification elements. The TiO2NWs/Au/CdSe@ZnS sensitized
structure could adequately absorb light energy and dramatically depress electron
hole recombination, resulting in evidently enhanced photocurrent intensity of the
immunosensing electrode. While target Ag were detected, the Ab2@V(2+) conjugates
could significantly decrease the photocurrent detection signal because of strong
electron-withdrawing property of V(2+) coupled with evident steric hindrance of
Ab2. Thanks to synergy effect of TiO2NWs/Au/CdSe@ZnS sensitized structure and
quenching effect of Ab2@V(2+) conjugates, the well-established
photoelectrochemical immunoassay exhibited a low detection limit of 0.0039 U/mL
with a wide linear range from 0.01 U/mL to 200 U/mL for target Ag detection. This
proposed photoelectrochemical protocol also showed good reproducibility,
specificity and stability, and might be applied to detect other important
biomarkers.
PMID- 26433067
TI - Label free electrochemical aptasensor for ultrasensitive detection of
ractopamine.
AB - A label free electrochemical (EC) aptasensor for ultrasensitive detection of
ractopamine (RAC) was developed. A special immobilization media consisting of
gold nanoparticles/poly dimethyl diallyl ammonium chloride-graphene composite
(AuNPs/PDDA-GN) was utilized to improve conductivity and performance of the
biosensor. The RAC aptamer was attached on AuNPs of the composite membrane via Au
S bond. The fabrication process of the EC aptasensor was characterized by
electrochemical impedance spectroscopy and cyclic voltammetry. The peak currents
obtained by differential pulse voltammetry decreased linearly with the increasing
of RAC concentrations and the sensor responds approximately logarithmically over
a wide dynamic range of RAC concentration from 1.0 * 10(-12)mol/L to 1.0 * 10(
8)mol/L. The linear correlation coefficient of the developed aptasensor was
0.998, the limit of detection was 5.0 * 10(-13)mol/L. The proposed EC aptasensor
displayed good stability, reproducibility and robust operation in animal urine.
Particularly, the generality of the fabrication approach of electrochemical
aptasensor is highlighted with a further example for illegal drugs detection via
the aptamer identification.
PMID- 26433068
TI - Highly sensitive and simultaneous electrochemical determination of 2-aminophenol
and 4-aminophenol based on poly(l-arginine)-beta-cyclodextrin/carbon
nanotubes@graphene nanoribbons modified electrode.
AB - Owing to the similar characteristics and physiochemical property of 2-aminophenol
(2-AP) and 4-aminophenol (4-AP), the highly sensitive simultaneous
electrochemical determination of 2- and 4-AP is a great challenge. In this paper,
by electropolymerizing beta-cyclodextrin (beta-CD) and l-arginine (l-Arg) on the
surface of carbon nanotubes@graphene nanoribbons (CNTs@GNRs) core-shell
heterostructure, a P-beta-CD-l-Arg/CNTs@GNRs nanohybrid modified electrode was
prepared successfully, and it could exhibit the synergetic effects of beta-CD
(high host-guest recognition and enrichment ability), l-Arg (excellent
electrocatalytic activity) and CNTs@GNRs (prominent electrochemical properties
and large surface area), the P-beta-CD-l-Arg/CNTs@GNRs modified electrode was
used in the electrochemical determination of 2- and 4-AP, the results
demonstrated that the highly sensitive and simultaneous determination of 2- and 4
AP is successfully achieved and the modified electrode has a linear response
range of 25.0-1300.0 nM for both 2- and 4-AP, and the detection limits of 2- and
4-AP obtained in this work are 6.2 and 3.5 nM, respectively.
PMID- 26433069
TI - Quantitative determination of uric acid using CdTe nanoparticles as fluorescence
probes.
AB - A convenient enzymatic optical method for uric acid detection was developed based
on the fluorescence quenching of ligand-capped CdTe nanoparticles by H2O2 which
was generated from the enzymatic reaction of uric acid. The interactions between
the CdTe nanoparticles capped with different ligands (glutathione, 3
mercaptopropionic acid, and thioglycerol) and H2O2 were investigated. The
fluorescence quenching studies of GSH-capped CdTe nanoparticles demonstrated an
excellent sensitivity to H2O2. The effects of uric acid, uricase and H2O2 on the
fluorescence intensity of CdTe nanoparticles were also explored. The detection
conditions, reaction time, pH value, incubation period and the concentration of
uricase and uric acid were optimized. The detection limit of uric acid was found
to be 0.10 uM and the linear range was 0.22-6 uM under the optimized experimental
conditions. These results typify that CdTe nanoparticles could be used as a
fluorescent probe for uric acid detection.
PMID- 26433070
TI - Sensitive and rapid detection of staphylococcus aureus in milk via cell binding
domain of lysin.
AB - Staphylococcus aureus (S. aureus) is an important food-borne pathogen in dairy
products contaminated through raw ingredients or improper food handling. Rapid
detection of S. aureus with high sensitivity is of significance for food quality
and safety. In this study, a new method was developed for detecting S. aureus in
milk by coupling immunomagnetic separation with enzyme linked cell wall binding
domain (CBD) of lysin plyV12, which can bind to S. aureus with high affinity.
There are millions of binding sites present on the cell surface of S. aureus for
the CBD attachment, which greatly improves the detection sensitivity. The method
has the overall testing time of only 1.5h with the detection limit of 4 *
10(3)CFU/mL in spiked milk. Because it is simple, rapid and sensitive, this
method could be used for the detection of S. aureus in various food samples.
PMID- 26433071
TI - Nickel/cobalt oxide-decorated 3D graphene nanocomposite electrode for enhanced
electrochemical detection of urea.
AB - A NiCo2O4 bimetallic electro-catalyst was synthesized on three-dimensional
graphene (3D graphene) for the non-enzymatic detection of urea. The structural
and morphological properties of the NiCo2O4/3D graphene nanocomposite were
characterized by X-ray diffraction, Raman spectroscopy, and scanning electron
microscopy. The NiCo2O4/3D graphene was deposited on an indium tin oxide (ITO)
glass to fabricate a highly sensitive urea sensor. The electrochemical properties
of the prepared electrode were studied by cyclic voltammetry. A high sensitivity
of 166 MUAmM(-)(1)cm(-)(2) was obtained for the NiCo2O4/3D graphene/ITO sensor.
The sensor exhibited a linear range of 0.06-0.30 mM (R(2)=0.998) and a fast
response time of approximately 1.0 s with a detection limit of 5.0 uM.
Additionally, the sensor exhibited high stability with a sensitivity decrease of
only 5.5% after four months of storage in ambient conditions. The urea sensor
demonstrates feasibility for urea analysis in urine samples.
PMID- 26433072
TI - Role of bioactive lipid mediators in obese adipose tissue inflammation and
endocrine dysfunction.
AB - White adipose tissue is recognized as an active endocrine organ implicated in the
maintenance of metabolic homeostasis. However, adipose tissue function, which has
a crucial role in the development of obesity-related comorbidities including
insulin resistance and non-alcoholic fatty liver disease, is dysregulated in
obese individuals. This review explores the physiological functions and molecular
actions of bioactive lipids biosynthesized in adipose tissue including
sphingolipids and phospholipids, and in particular fatty acids derived from
phospholipids of the cell membrane. Special emphasis is given to polyunsaturated
fatty acids of the omega-6 and omega-3 families and their conversion to bioactive
lipid mediators through the cyclooxygenase and lipoxygenase pathways. The
participation of omega-3-derived lipid autacoids in the resolution of adipose
tissue inflammation and in the prevention of obesity-associated hepatic
complications is also thoroughly discussed.
PMID- 26433074
TI - The relationship between wing length, blood meal volume, and fecundity for seven
colonies of Anopheles species housed at the Armed Forces Research Institute of
Medical Sciences, Bangkok, Thailand.
AB - Established colonies of Anopheles campestris, Anopheles cracens, Anopheles dirus,
Anopheles kleini, Anopheles minimus, Anopheles sawadwongporni, and Anopheles
sinensis are maintained at the Armed Forces Research Institute of Medical
Sciences (AFRIMS). Females were provided blood meals on human blood containing
citrate as an anticoagulant using an artificial membrane feeder. The mean wing
length, used as an estimate of body size, for each species was compared to blood
feeding duration (time), blood meal volume, and numbers of eggs oviposited.
Except for An. campestris and An. cracens, there were significant interspecies
differences in wing length. The mean blood meal volumes (mm(3)) of An. kleini and
An. sinensis were significantly higher than the other 5 species. For all species,
the ratios of unfed females weights/blood meal volumes were similar (range: 0.76
0.88), except for An. kleini (1.08) and An. cracens (0.52), that were
significantly higher and lower, respectively. Adult females were allowed to feed
undisturbed for 1, 3, and 5min intervals before blood feeding was interrupted.
Except for An. campestris and An. sawadwongporni, the number of eggs oviposited
were significantly higher for females that fed for 3min when compared to those
that only fed for 1min. This information is critical to better understand the
biology of colonized Anopheles spp. and their role in the transmission of malaria
parasites as they relate to the relative size of adult females, mean volumes of
blood of engorged females for each of the anopheline species, and the effect of
blood feeding duration on specific blood meal volumes and fecundity.
PMID- 26433073
TI - MicroRNA regulation of F-box proteins and its role in cancer.
AB - MicroRNAs (miRNAs) are small endogenous non-coding RNAs, which play critical
roles in cancer development by suppressing gene expression at the post
transcriptional level. In general, oncogenic miRNAs are upregulated in cancer,
while miRNAs that act as tumor suppressors are downregulated, leading to
decreased expression of tumor suppressors and upregulated oncogene expression,
respectively. F-box proteins function as the substrate-recognition components of
the SKP1-CUL1-F-box (SCF)-ubiquitin ligase complex for the degradation of their
protein targets by the ubiquitin-proteasome system. Therefore F-box proteins and
miRNAs both negatively regulate target gene expression post-transcriptionally.
Since each miRNA is capable of fine-tuning the expression of multiple target
genes, multiple F-box proteins may be suppressed by the same miRNA. Meanwhile,
one F-box proteins could be regulated by several miRNAs in different cancer
types. In this review, we will focus on miRNA-mediated downregulation of various
F-box proteins, the resulting stabilization of F-box protein substrates and the
impact of these processes on human malignancies. We provide insight into how the
miRNA: F-box protein axis may regulate cancer progression and metastasis. We also
consider the broader role of F-box proteins in the regulation of pathways that
are independent of the ubiquitin ligase complex and how that impacts on
oncogenesis. The area of miRNAs and the F-box proteins that they regulate in
cancer is an emerging field and will inform new strategies in cancer treatment.
PMID- 26433075
TI - Mansonella ozzardi in Neotropical region of Argentina: Prevalence through time
(1986-2010).
AB - Human filariasis caused by Mansonella ozzardi is a parasitic infection of a
controversial pathology and poorly studied in Argentina. The aim of this study
was not only to obtain data of the prevalence of M. ozzardi in Northwestern
Argentina through comparison of infection rates in relation to sex and age group
determining the range of distribution of mansonelliasis in the region but also to
investigate the prevalence of the cases over time. Through field work carried
between 1986 and 2010 by technicians of the National Ministry of Health, aiming
to detect active cases of malaria in the Northwestern Argentina, blood samples
were taken for smear and thick blood. 417 blood samples were examined, 381 of
them (91.4%) were positive for M. ozzardi. The highest prevalence was found in
Salta province (92.3%) mainly affecting the male sex (92.6%) and the age groups
comprised between 48-57 years (97.0%) and >= 68 (90.7%). The paired t-test and
Spearman coefficients showed significant differences in prevalence according to
sex (t=2.677; p=0.015), and according infection rates in males and females/age
(r=0.994; p=0.001; r=0.994, p=0.001, respectively). The prevalence over time
showed a general pattern with the highest cases in 1986, decreasing later during
the following years. Aguas Blancas, El Oculto and San Ramon de la Nueva Oran,
exhibited a pattern of prevalence according to the general trend but Salvador
Mazza and Tartagal, which are also localities close to the border with Bolivia,
showed peaks of cases up to 2010. These results provide relevant information
about M. ozzardi in Argentina, demonstrating not only its presence and endemicity
after almost 100 years from its discovery in the country, but also its wide range
of distribution in the region.
PMID- 26433076
TI - An epidemiological study of dengue in Delhi, India.
AB - Delhi, the capital of India, is an important metropolitan hub for major financial
and sociocultural exchanges, offering challenging threats to current public
health infrastructure. In recent past, an upsurge of dengue cases in Delhi posed
a significant menace to the existing dengue control policies. To reform the
control strategies and take timely intervention to prevent future epidemics, an
epidemiological study on the proportion of both asymptomatic and symptomatic
dengue infections in selected population was conducted. The aim of the study was
to investigate and assess the epidemiology of dengue infection and to estimate
the proportion of asymptomatic and symptomatic dengue infections in Delhi. In
this study, around 50 confirmed dengue cases, a total of 2125 individuals as
household and neighbourhood contacts, with or without dengue febrile illness,
were finger pricked and serologically detected as dengue positive or negative
using SD Duo Bioline Rapid Diagnostic Test (SD Inc, Korea) with NS1, IgM & IgG
combo test, which detected dengue virus antigen and antibodies to dengue virus in
human blood. Out of 2125 individuals, 768 (36.1%) individuals showed positive
dengue test with past (25.5%), primary (1.88%) or secondary (8.8%) dengue
infections. Higher percentage of IgG was found in age groups 15-24 years and 25
50 years (36% each). Infants (<1 year) presented higher incidence of new
infections (22% of NS1+IgM positives) as compared to adults. Further analysis
revealed that out of the 226 newly infected cases (including NS1 and IgM
positives), 142 (63%) were asymptomatic and 84 (37%) were symptomatic, as per WHO
guidelines. Our findings also suggest that out of the total population screened,
10.6% dengue infection was either primary or secondary. On the basis of these
results, it may be hypothesized that there are large number of asymptomatic
dengue infections in the community as compared to reported symptomatic cases in
Delhi. For the effective control of dengue transmission in such community like
Delhi where dengue epidemics have frequently been encountered, it is essential to
ascertain the proportion of asymptomatic dengue infections which may act as a
reservoir for dengue transmission, as well as threat for developing dengue
haemorrhagic fever (DHF).
PMID- 26433077
TI - Evidence of selection on phenotypic plasticity and cost of plasticity in response
to host-feeding sources in the major Chagas disease vector Triatoma infestans.
AB - Phenotypic plasticity is the ability of a genotype to display alternative
phenotypes in different environments. Understanding how plasticity evolves and
the factors that favor and constrain its evolution have attracted great interest.
We investigated whether selection on phenotypic plasticity and costs of
plasticity affect head and wing morphology in response to host-feeding sources in
the major Chagas disease vector Triatoma infestans. Full-sib families were
assigned to blood-feeding on either live pigeons or guinea pigs throughout their
lives. We measured diet-induced phenotypic plasticity on wing and head size and
shape; characterized selection on phenotypic plasticity for female and male
fecundity rates, and evaluated costs of plasticity. Wing size and shape variables
exhibited significant differences in phenotypic plasticity associated with host
feeding source in female and male bugs. Evidence of selection on phenotypic
plasticity was detected in head size and shape for guinea pig-fed females. A
lower female fecundity rate was detected in more plastic families for traits that
showed selection on plasticity. These results provide insights into the
morphological phenotypic plasticity of T. infestans, documenting fitness
advantages of head size and shape for females fed on guinea pigs. This vector
species showed measurable benefits of responding plastically to environmental
variation rather than adopting a fixed development plan. The presence of cost of
plasticity suggests constraints on the evolution of plasticity. Our study
indicates that females fed on guinea pigs (and perhaps on other suitable
mammalian hosts) have greater chances of evolving under selection on phenotypic
plasticity subject to some constraints.
PMID- 26433078
TI - A Petal-like Calyceal Diverticulum.
AB - Calyceal diverticula are rare outpouchings of the upper collecting system that
likely have a congenital origin. They are usually single cystic lesions
accompanied by stones inside them and located in the upper pole calyces. We
present a case containing a petal-like cystic lesion with multiple septa in the
lower pole of the left kidney, which was confirmed as calyceal diverticulum by
computed tomography urography and intraoperative findings.
PMID- 26433079
TI - Medicinal Leech Therapy for Glans Penis Congestion After Primary Bladder
Exstrophy-Epispadias Repair in an Infant: A Case Report.
AB - Many postoperative complications have been reported after repair of classic
bladder exstrophy. We present a case of medicinal leech therapy for glans penis
congestion following exstrophy repair in an infant. A 2-week-old male with
classic bladder exstrophy underwent complete primary repair. On postoperative day
1, he developed rapidly worsening glans penis venous congestion. Medicinal leech
therapy was instituted with antibiotics and blood transfusions to maintain a
hematocrit >30%. After 24 hours, venous congestion improved and therapy was
discontinued. The patient's remaining hospital course was uncomplicated.
Medicinal leeches are an effective therapy to relieve glans penis venous
congestion.
PMID- 26433080
TI - Quadruple Orchidopexy for Torsion Testis in an Adolescent With Polyorchidism: A
Case Report.
AB - We report a case of testicular torsion in an adolescent with polyorchidism,
specifically quadorchidism. Sonographic and intraoperative images are provided to
describe the presentation and management of this case, while the challenges and
pitfalls with this clinical scenario are discussed.
PMID- 26433081
TI - Dorsal Lumbotomy Incision for Partial Nephrectomy in Patients With Small
Posterior Renal Masses.
AB - OBJECTIVE: To describe our single-surgeon experience with dorsal lumbotomy, an
uncommonly utilized muscle-sparing incision, for open partial nephrectomy.
MATERIALS AND METHODS: We retrospectively identified patients who underwent
partial nephrectomy through dorsal lumbotomy incision by a single surgeon from
September 2012 through April 2014. Clinicopathologic characteristics were
recorded along with early postoperative outcomes including hospital length of
stay and narcotic requirement. RESULTS: Twenty-four patients were identified for
analysis. Median operative time was 71 minutes (interquartile range [IQR]: 63-91
minutes), and median estimated blood loss was 250 mL (IQR: 100-438 mL). Median
length of stay was 1.2 days (IQR: 0.94-2.0 days) and median narcotic requirement
was 17 mg of oral morphine equivalents (IQR: 4.9-43 mg). Overall perioperative
complication rate was 25% including 1 major (Clavien III-V) complication.
CONCLUSION: Partial nephrectomy via dorsal lumbotomy incision is a safe and
feasible option for small posterior renal masses when performed by an experienced
surgeon. The drawbacks of this approach are limited access to the renal hilum and
risk of injury to the iliohypogastric or subcostal nerves. Dorsal lumbotomy is
associated with postoperative outcomes equivalent to or better than standard
operative approaches and should be considered a viable surgical approach in
selected cases.
PMID- 26433082
TI - High Prevalence of Opaline Silica in Urinary Stones From Burkina Faso.
AB - OBJECTIVE: To underline peculiar composition of kidney stones and to propose an
epidemiologic study of urinary stones in West African countries, where
epidemiologic studies are scarce. Only few data are available regarding stone
composition in sub-Saharan countries. Recently, a set of 100 stones consecutively
removed by surgery in the Department of Urology of the University Hospital of
Ouagadougou in Burkina Faso were collected for physical analysis, which provided
the opportunity to obtain an epidemiologic profile of stone composition in this
country. MATERIALS AND METHODS: A total of 100 stones from 64 men, 22 women, 10
boys, and four girls were analyzed by morphologic examination, infrared
spectroscopy, and electron microscopy in our laboratory. The results were
considered by sex and separately for adults and children. RESULTS: Sixty-five
percent of the 100 stones contained calcium oxalate as the main component.
Interestingly, the second main component was opaline silica (18%). Furthermore,
opaline silica was identified in any proportion in 48% of the stones. The
prevalence was sex and age dependent. Opaline silica was detected as the main
component in 42% of the nuclei, which underlines its role as one of the main
components involved in the initiation of calculi in this country. CONCLUSION: For
the first time, a dramatically high occurrence of a "scarce" urinary stone
component, namely opaline silica, was reported in a series of consecutive calculi
from a single country. We propose that a regular consumption of clay could be the
origin of this phenomenon in these populations.
PMID- 26433083
TI - Malignant Mesothelioma of Spermatic Cord in an Elderly Man With a History of
Asbestos Exposure.
AB - We report a case of malignant mesothelioma of the spermatic cord in 80-year-old
man presented with retained testis, hydrocele, and right inguinal mass. The
patient had a long history of asbestos exposure as a railway worker. The patient
was submitted to inguinal radical orchiectomy. One year after surgery, the
patient is alive without signs of disease. Malignant mesothelioma of spermatic
cord is a very rare disease, but this diagnosis should be suspected in patient
with a history of asbestos exposure.
PMID- 26433084
TI - Universal dispersing agent for electrophoretic deposition of inorganic materials
with improved adsorption, triggered by chelating monomers.
AB - Poly[1-[4-(3-carboxy-4-hydroxyphenylazo)benzenesulfonamido]-1,2-ethanediyl,
sodium salt] (PAZO) is a polymeric functional material with a number of unique
physical properties, which attracted significant interest of different scientific
communities. Films of PAZO were deposited by anodic electrophoretic deposition
(EPD) under constant current and constant voltage conditions. The deposition
kinetics was analyzed under different conditions and the deposition mechanism was
discussed. New strategy was developed for the EPD of different inorganic
materials and composites using PAZO as a dispersing, charging, binding and film
forming agent. It was found that PAZO exhibits remarkable adsorption on various
inorganic materials due to the presence of chelating salicylate ligands in its
molecular structure. The salicylate ligands of PAZO monomers provide multiple
adsorption sites by complexation of metal atoms on particle surfaces and allow
for efficient electrosteric stabilization of particle suspensions. The remarkable
performance of PAZO in its application in EPD have been exemplified by deposition
of a wide variety of inorganic materials including the single element oxides
(NiO, ZnO, Fe2O3) the complex oxides (Al2TiO5, BaTiO3, ZrSiO4, CoFe2O4) different
nitrides (TiN, Si3N4, BN) as well as pure Ni metal and hydrotalcite clay. The use
of PAZO can avoid limitation of other dispersing agents in deposition and co
deposition of different materials. Composite films were obtained using PAZO as a
co-dispersant for different inorganic materials. The deposit composition,
microstructure and deposition yield can be varied. The EPD method offers the
advantages of simplicity, high deposition rate, and ability to deposit thin or
thick films.
PMID- 26433085
TI - Preparation of flower-like ZnO architectures assembled with nanosheets for
enhanced photocatalytic activity.
AB - As an important semiconductor metal oxide, various methods have been developed
for preparation of ZnO architectures owing to their excellent properties and
extensive applications. In this paper, two kinds of 3D flower-like ZnO
architectures assembled with numerous nanosheets were successfully synthesized by
a simple hydrothermal route assisted by sodium dodecyl sulfate (SDS), origining
from the different alkali environment created by urea and hexamine (HMT). SEM and
TEM results revealed that the two products had hydrangea-like and rose-like
nanostructures with uniform particle sizes, respectively. XRD results confirmed
that the growth process of ZnO involved a phase transformation from intermediate
compound basic zinc carbonate to ZnO. Base on the experimental results, the
formation mechanisms of two kinds of flower-like ZnO undergoing nucleation,
oriented growth and self-assembly processes were discussed. The photocatalytic
results indicated that both samples exhibited high photocatalytic activities and
good cycling stability for the degradation of rhodamine B (RhB), which was almost
completely degraded within 25min, in comparison to those milled samples (above
45min). The excellent performances were mainly ascribed to their unique
nanostructure, good stability, and uniform particle size.
PMID- 26433086
TI - How B-Type Natriuretic Peptide (BNP) and Body Weight Changes Vary in Heart
Failure With Preserved Ejection Fraction Compared With Reduced Ejection Fraction:
Secondary Results of the HABIT (HF Assessment With BNP in the Home) Trial.
AB - BACKGROUND: Heart failure is a common cause of hospitalization and can be divided
into types with preserved and reduced ejection fraction (HFpEF and HFrEF,
respectively). In this subanalysis of the HABIT (Heart Failure Assessment With
BNP in the Home) trial, we examined the differences between home B-type
natriuretic peptide (BNP) testing and weight monitoring in patients with HFpEF
and with HFrEF before decompensation. METHODS AND RESULTS: This was a
retrospective review of patients with HFpEF and HFrEF from the HABIT trial. The
HFpEF patients compared with HFrEF patients were older and more obese and had
lower baseline BNP values. Intra-individual BNP dispersion (spread of
distribution over time) was greater in HFpEF than in HFrEF owing to rapid
fluctuations (within 3 days). Slowly varying changes in BNP (estimated by a
moving average) were equally predictive of ADHF risk in both HFpEF and HFrEF.
However, in HFpEF, a rapid rise in BNP >200 pg/mL within 3 days was associated
with an increased risk of acute decompensated heart failure (ADHF; hazard ratio
4.0), whereas a similar association was not observed in HFrEF. Weight gain >=5 lb
in 3 days had a high specificity but low sensitivity for ADHF in both HFpEF and
HFrEF, whereas a lower threshold of >=2 lb weight gain over 3 days in patients
with HFpEF (but not HFrEF) was a moderately sensitive cutoff associated with
decompensation (60% sensitivity). CONCLUSIONS: Patients with HFpEF and HFrEF have
variations in their BNP and weight before decompensation. The rapid time scale
behaves differently between the groups. In those with HFpEF, a 3-day period
characterized by >=2 lb weight gain and/or >200 pg/mL BNP rise was significantly
associated with decompensation. Future prospective studies investigating
different weight and BNP cutoffs for home monitoring of HFpEF and HFrEF patients
should be performed to fully learn the value of BNP changes before clinical
deompensation.
PMID- 26433087
TI - Cardiac Resynchronization in Different Age Groups: A MADIT-CRT Long-Term Follow
Up Substudy.
AB - BACKGROUND: Cardiac resynchronization with defibrillators (CRT-D) reduces heart
failure and mortality compared with defibrillators alone. Whether this applies to
all ages is unclear. METHODS AND RESULTS: We assessed the association of age on
heart failure and death as a post hoc analysis of the MADIT-CRT follow-up study,
in which 1,281 patients with class I/II heart failure (HF) were randomized to CRT
D or implantable cardioverter-defibrillators alone. Different age groups (<60, 60
74, and >=75 years) were evaluated over 7 years for mortality and HF events.
Among the 3 age groups, there were 399, 651, and 231 patients, respectively. We
compared events with the use of a multivariate regression model. CRT-D compared
with defibrillators alone significantly reduced the composite of HF or death
across all age groups: <60 years: relative risk reduction (RRR) = 36%; 60-74
years: RRR = 61%; >=75 years: RRR = 56%. CRT-D significantly reduced HF in all
age groups: <60 years: RRR = 49%; 60-74 years: RRR = 62%; >=75 years: RRR = 74%.
CRT-D was associated with significant mortality reduction only in the 60-74 year
age group: RRR = 59%. CONCLUSIONS: CRT-D reduced HF events and the composite of
mortality or HF events during long-term follow-up in all age groups. CRT-D
reduced mortality only in the 60-74 year age group.
PMID- 26433088
TI - Mixed-mode I+II fracture characterization of human cortical bone using the Single
Leg Bending test.
AB - Mixed-mode I+II fracture characterization of human cortical bone was analyzed in
this work. A miniaturized version of the Single Leg Bending test (SLB) was used
owing to its simplicity. A power law criterion was verified to accurately
describe the material fracture envelop under mixed-mode I+II loading. The crack
tip opening displacements measured by digital image correlation were used in a
direct method to determine the cohesive law mimicking fracture behavior of
cortical bone. Cohesive zone modeling was used for the sake of validation.
Several fracture quantities were compared with the experimental results and the
good agreement observed proves the appropriateness of the proposed procedure for
fracture characterization of human bone under mixed-mode I+II loading.
PMID- 26433089
TI - Degradation and swelling issues of poly-(d,l-lactide)/beta-tricalcium
phosphate/calcium carbonate composites for bone replacement.
AB - Recently a tri-phase material consisting of poly-(d,l-lactide) (PDLLA), beta
tricalcium phosphate (beta-TCP), and calcium carbonate (CC) was proposed as a
novel bone substitute candidate. beta-TCP is suitable because of its bone-like
mineral phase, PDLLA is introduced as a biodegradable adhesive phase, and CC is
essential for buffering the acidic degradation of the lactate component. We
hypothesize that the amounts of the three different components in the composite
material must be carefully balanced in order to avoid issues such as accelerated
degradation or pronounced volumetric swelling. To prove this, granulates made of
different mixing ratios of the tri-phase compound were prepared by grinding.
Specimens of the different compounds were manufactured by a hot pressing process.
The bending strength of the specimens was determined before and after storing in
demineralized water and phosphate buffered saline (PBS). The particle size of the
compound granulates was smaller than 100um. A ratio of 60wt% of the PDLLA
component indicated the best compromise between stability of test specimens based
on a strong melting network and bone-like properties. The specimens exhibited a
bending strength up to 90MPa. The strength increased with an increasing ratio of
beta-TCP to calcium carbonate (based on 60wt% PDLLA). A vast volumetric swelling
up to 40%, and thus a huge reduction of the bending strength, was observed during
the storage of specimens in PBS. A swelling and thus a volume increase could be
critical, especially for using the tri-phase bone substitute compound as 3D
scaffold with defined dimensions. This must be considered with regard to the
composition of the compound and the scaffold design.
PMID- 26433091
TI - Modeling dynamical electron scattering with Bethe potentials and the scattering
matrix.
AB - Bethe potentials were introduced by Bethe in 1928 as a first order perturbation
approach to reducing the number of diffracted beams in dynamical electron
scattering problems. The approach starts from the Bloch wave representation, and
uses a threshold criterion to split the diffracted beams into two subsets, namely
strong and weak beams. Since the use of Bloch wave based Bethe potentials for
defect simulations is somewhat tedious, this paper applies the perturbation
approach to the scattering matrix formalism, which is more readily adaptable for
defect image simulations. The size of the dynamical matrix, and hence the
computation time, can be reduced significantly. A threshold criterion for the
separation of scattered beams into strong and weak sets is introduced. A general
guideline in setting the threshold for strong or weak beam selection is discussed
along with several parameters that may influence the threshold values, such as
atomic number, accelerating voltage, structure complexity, incident beam tilt and
temperature.
PMID- 26433090
TI - Transcriptional enhancers: functional insights and role in human disease.
AB - In recent years, studies of cis-regulatory mechanisms have evolved from a
predominant focus on promoter regions to the realization that spatial and
temporal gene regulation is frequently driven by long-range enhancer clusters
that operate within chromosomal compartments. This increased understanding of
genome function, together with the emergence of technologies that enable whole
genome sequencing of patients' DNAs, open the prospect of dissecting the role of
cis-regulatory defects in human disease. In this review we discuss how recent
epigenomic studies have provided insights into the function of transcriptional
enhancers. We then present examples that illustrate how integrative genomics can
help uncover enhancer sequence variants underlying Mendelian and common polygenic
human disease.
PMID- 26433092
TI - Involvement of the osrR gene in the hydrogen peroxide-mediated stress response of
Corynebacterium glutamicum.
AB - A transcriptional profile of the H2O2-adapted Corynebacterium glutamicum HA
strain reveals a list of upregulated regulatory genes. Among them, we selected
ORF NCgl2298, designated osrR and analyzed its role in H2O2 adaptation. The osrR
deleted (DeltaosrR) mutant had defective growth in minimal medium, which was even
more pronounced in an osrR deletion mutant of an HA strain. The DeltaosrR strain
displayed increased sensitivity to H2O2. In addition to H2O2 sensitivity, the
DeltaosrR strain was found to be temperature-sensitive at 37 degrees C. 2D-PAGE
analysis of the DeltaosrR mutant found that MetE and several other proteins
involved in redox metabolism were affected by the mutation. Accordingly, the
NADPH/NADP(+) ratio of the DeltaosrR strain (0.85) was much lower than that of
the wild-type strain (2.01). In contrast, the NADH/NAD(+) ratio of the mutant
(0.54) was considerably higher than that of the wild-type (0.21). Based on these
findings, we propose that H2O2-detoxifying metabolic systems, excluding those
involving catalase, are present in C. glutamicum and are regulated, in part, by
osrR.
PMID- 26433093
TI - Profilin Regulates Apical Actin Polymerization to Control Polarized Pollen Tube
Growth.
AB - Pollen tube growth is an essential step during flowering plant reproduction,
whose growth depends on a population of dynamic apical actin filaments. Apical
actin filaments were thought to be involved in the regulation of vesicle fusion
and targeting in the pollen tube. However, the molecular mechanisms that regulate
the construction of apical actin structures in the pollen tube remain largely
unclear. Here, we identify profilin as an important player in the regulation of
actin polymerization at the apical membrane in the pollen tube. Downregulation of
profilin decreased the amount of filamentous actin and induced disorganization of
apical actin filaments, and reduced tip-directed vesicle transport and
accumulation in the pollen tube. Direct visualization of actin dynamics revealed
that the elongation of actin filaments originating at the apical membrane
decreased in profilin mutant pollen tubes. Mutant profilin that is defective in
binding poly-L-proline only partially rescues the actin polymerization defect in
profilin mutant pollen tubes, although it fully rescues the actin turnover
phenotype. We propose that profilin controls the construction of actin structures
at the pollen tube tip, presumably by favoring formin-mediated actin
polymerization at the apical membrane.
PMID- 26433094
TI - Repetitive Plantar Flexion Test as an Adjunct Tool for the Diagnosis of Common
Peroneal Nerve Entrapment Neuropathy.
AB - OBJECTIVE: The diagnosis of common peroneal nerve entrapment neuropathy (CPNEN)
is based on clinical symptoms and nerve conduction studies. However, nerve
conduction studies may not detect abnormalities. Under the hypothesis that
repetitive plantar flexion that loads the peroneal nerve (PN) at the entrapment
point without lumbar loading would be a useful CPNEN provocation test, we
evaluated the repetitive plantar flexion (RPF) test as an adjunct diagnostic tool
for CPNEN. The study design was a retrospective analysis of prospectively
collected data. METHODS: Our study population consisted of 18 consecutive
patients whose ipsilateral CPNEN improved significantly after PN neurolysis.
Using repetitive ankle plantar flexion as a CPNEN provocation test, results were
recorded as positive when it elicited numbness and/or pain in the affected area
of the PN. RESULTS: The RPF test induced symptoms on all affected sides in the
course of 57.4 seconds (range, 14-120 seconds). In 3 patients it induced numbness
in the affected area of the PN in the normal leg. Receiver operating
characteristic analysis showed that the diagnostic sensitivity and accuracy of
the test were 94.4% each. The suggested cutoff point was 110 seconds and the area
under the receiver operating characteristic curve was 0.97 (95% confidence
interval 0.93-1.02). The positive and the negative predictive values were 89.5%
and 94.1%, respectively. CONCLUSIONS: Our simple RPF test elicited the symptoms
of CPNEN and our provocation test helped to identify dynamic PN entrapment
neuropathy as the origin of intermittent claudication.
PMID- 26433095
TI - The Role of Therapeutic Hypothermia After Traumatic Spinal Cord Injury--A
Systematic Review.
AB - BACKGROUND: Traumatic spinal cord injury (SCI) is a devastating neurologic entity
characterized by a primary insult followed by a secondary pathologic cascade that
propagates further injury. Hypothermia has an established clinical role in
preventing SCI after cardiac arrest and thoracoabdominal aortic aneurysm repair,
yet its emergence as a potential neuroprotectant after spinal cord trauma remains
experimental. There are currently no pharmacologic interventions available to
prevent secondary mechanisms of injury after spinal cord trauma. METHODS:
Systematic review of literature. RESULTS: Experimental studies demonstrated that
hypothermia diminishes secondary pathomechanisms, such as ischemia, oxidative
stress, apoptosis, inflammation, and edema. Early onset and longer durations of
hypothermia as well as concomitant steroids or neural stem cell engraftment
combined with hypothermia appear to improve functional and histologic outcomes in
animal models of spinal cord trauma. Recent clinical studies provide evidence
that localized and systemic hypothermia may be applied safely and efficaciously
in patients with severe acute SCI. Randomized clinical trials are needed to
better evaluate optimal cooling parameters and the effectiveness of hypothermia
after traumatic SCI. CONCLUSION: Although variability exists in the literature,
therapeutic hypothermia most likely confers neuroprotection after spinal cord
trauma by diminishing the destructive secondary cascade. The available clinical
data suggest that regional and systemic hypothermia is a relatively safe and
feasible initial treatment modality for patients with acute SCI when combined
with surgical decompression/stabilization with or without steroids. However,
establishing a clinical role for therapeutic hypothermia after spinal cord trauma
will invariably depend on future well-designed, multicentered, randomized,
controlled clinical trial data.
PMID- 26433096
TI - Analysis of Decompressive Craniectomies with Subsequent Cranioplasties in the
Presence of Collagen Matrix Dural Substitute and Polytetrafluoroethylene as an
Adhesion Preventative Material.
AB - OBJECTIVE: Decompressive craniectomy is an established treatment for malignant
intracranial hypertension. Cranioplasty is performed once cerebral swelling has
resolved. Complications include infection, postoperative fluid collections,
hematoma, reoperation, and seizures. Our experience using a double layer
technique during craniectomy with a collagen matrix onlay dural substitute and
expanded polytetrafluoroethylene for antiadhesive properties during cranioplasty
was reviewed. METHODS: This is a retrospective chart review of 39 consecutive
patients who underwent craniectomy with placement of collagen matrix dural onlay
and expanded polytetrafluoroethylene and subsequent cranioplasty. Demographic
data, size of craniectomy defect, estimated blood loss, operative time, time
between operations, presence of dural tackups, and postoperative complications
were analyzed. RESULTS: Mean operative time was 132 minutes and estimated blood
loss was 112 mL. Overall complication rate was 25.6% and no mortality was
encountered. Nine patients had postoperative fluid collections measuring >= 10 mm
in thickness and/or 5 mm of midline shift. Two patients required reoperation for
these collections. Two patients developed infections requiring bone flap removal.
Three patients developed seizures after cranioplasty. Five patients required
shunt placement for hydrocephalus. CONCLUSIONS: Our dual layer closure technique
at time of decompressive craniectomy carries a similar reduction in operative
time and estimated blood loss when compared with cranioplasty series with other
antiadhesives present. The technique described enables easy dissection of the
musculocutaneous flap from the dural plane during cranioplasty and increases the
safety of the operation.
PMID- 26433097
TI - Occipitocervical Fusions in Elderly Patients: Mortality and Reoperation Rates
From a National Spine Registry.
AB - BACKGROUND: Several studies have shown excellent fusion rates in occipitocervical
(OC) fusions, but very little is reported on mortality and reoperation rates in
elderly patients. Our article reports these rates in elderly patients from a
national spine registry with a >2-year follow-up period. METHODS: Using data from
a spine implant registry developed at a large integrated health care system
(Kaiser Permanente), elderly patients (aged >= 65 years) with instrumented OC
fusions between January 1, 2009 and September 30, 2013 were identified. Patients'
demographics were extracted from the registry. From chart review, the types of
hardware and bone graft used, as well as mortality and reoperations rates were
noted. RESULTS: Forty-seven patients with OC fusions were identified. Six
patients had reoperations related to their fusions. Two occurred in the same
patient, which resulted in a 14.9% reoperation rate. There were a total of 13
deaths (27.7%), with 7 occurring within 3 months, but only 4 (8.5%) related to
the procedure. Bone morphogenetic protein was used in 29 patients (85.3%, 29/34).
All cases used occipital plates with rods and screws. There was 1 nonunion.
CONCLUSIONS: Mortality rate was 27.7% and the reoperations rate was 14.9% for
patients who underwent OC fusions with age >65 years and were observed for >2
years. These numbers are much higher than in younger patients, but reflect a
higher mortality due to their comorbidities and from progression of their disease
for cases of metastasis to the spine.
PMID- 26433098
TI - The Incidence of Neurologic Susceptibility to a Skull Defect.
AB - OBJECTIVE: To determine whether there is a measureable change in neurologic
function after cranioplasty. METHODS: This is a prospective single-surgeon,
single-center study. Fifty patients who required a cranioplasty procedure were
assessed neurologically within 72 hours before and 7 days after surgery. The
assessment tools were the Functional Independence Measure (FIM) and the Cognitive
assessment report (Cognistat). The scores for both assessments were calculated
and then compared before and after surgery. RESULTS: FIM assessment was performed
on all fifty patients, and a Cognistat assessment was performed on 47 patients.
Most improvements were seen in the Cognistat scores; however, there appeared to
be no specific areas in which there was consistent improvement. There were
substantial improvements in the Cognistat assessment in 9 patients. One patient
had a much-improved FIM assessment (improved from 18 to 34), but a Cognistat
assessment was not possible because of poor neurologic function. These results
suggested that improvements after cranioplasty were more likely to occur in the
domain of cognitive function than motor function, although overall these results
did not reach statistically significance. Bifrontal (vs. unilateral)
cranioplasty, timing between decompression and cranioplasty, and age of the
patients did not appear to affect the postoperative FIM scores, after we adjusted
for preoperative FIM scores and surgical complications. CONCLUSIONS: A small but
significant number of patients appear to improve clinically after cranioplasty.
Neurologic susceptibility to a skull defect may be more common than had been
appreciated previously.
PMID- 26433099
TI - China's Medical Education and INR Training.
PMID- 26433100
TI - Gastroenterology training recruitment -- a UK perspective.
PMID- 26433101
TI - Reply: To PMID 25921370.
PMID- 26433102
TI - An unusual case of colonic hemorrhage.
PMID- 26433103
TI - A rare case of gastric ulcerative mass.
PMID- 26433104
TI - Research in gastroenterology fellowship training.
PMID- 26433105
TI - A rare cause of postprandial abdominal pain and nausea.
PMID- 26433106
TI - Was adjuvant immunotherapy really effective to reduce hepatocellular carcinoma
recurrence?
PMID- 26433107
TI - Multiple liver lesions after oxaliplatin-based chemotherapy for colorectal
cancer.
PMID- 26433108
TI - Reply: To PMID 25747273.
PMID- 26433109
TI - An enlarging liver in a young diabetic male.
PMID- 26433110
TI - Reply: To PMID 25836985.
PMID- 26433111
TI - Adjuvant immunotherapy for postoperative hepatocellular carcinoma.
PMID- 26433112
TI - An uncommon cause of infantile jaundice.
PMID- 26433114
TI - Tackling extremes: challenges for ecological and evolutionary research on extreme
climatic events.
AB - Extreme climatic events (ECEs) are predicted to become more frequent as the
climate changes. A rapidly increasing number of studies - though few on animals -
suggest that the biological consequences of ECEs can be severe. However,
ecological research on the impacts of ECEs has been limited by a lack of
cohesiveness and structure. ECEs are often poorly defined and have often been
confusingly equated with climatic variability, making comparison between studies
difficult. In addition, a focus on short-term studies has provided us with little
information on the long-term implications of ECEs, and the descriptive and
anecdotal nature of many studies has meant it is still unclear what the key
research questions are. Synthesizing the current state of work is essential to
identify ways to make progress. We conduct a synthesis of the literature and
discuss conceptual and practical challenges faced by research on ECEs. We
consider three steps to advance research. First, we discuss the importance of
choosing an ECE definition and identify the pros and cons of 'climatological' and
'biological' definitions of ECEs. Secondly, we advocate research beyond short
term descriptive studies to address questions concerning the long-term
implications of ECEs, focussing on selective pressures and phenotypically plastic
responses and how they might differ from responses to a changing climatic mean.
Finally, we encourage a greater focus on multi-event studies that help us
understand the implications of changing patterns of ECEs, through the combined
use of modelling, experimental and observational field studies. This study aims
to open a discussion on the definitions, questions and methods currently used to
study ECEs, which will lead to a more cohesive approach to future ECE research.
PMID- 26433113
TI - Improved cardiovascular outcomes following temporal advances in lipid-lowering
therapy in a genetically-characterised cohort of familial hypercholesterolaemia
homozygotes.
AB - BACKGROUND AND AIMS: There is a paucity of data concerning the influence of lipid
lowering therapy on cardiovascular (CV) outcomes in patients with homozygous
familial hypercholesterolaemia (FH). To redress this a retrospective analysis was
undertaken of the demographic features, lipid levels, low density lipoprotein
receptor and Autosomal Recessive Hypercholesterolaemia gene mutations, CV
outcomes and vital status of 44 FH homozygotes referred to a single centre in the
UK between 1964 and 2014. METHODS: Data were obtained from past publications,
case records and death certificates. Differences in categorical and continuous
variables between living and dead patients were analysed using Fisher's exact
test and an independent t-test respectively. RESULTS: During the 50 years covered
by this survey 13 patients have died, 30 are still alive and 1 was lost to follow
up. The mean age of Alive patients was 32.6 +/- 11.5 versus 28.3 +/- 14.9 years
in Dead ones (P = 0.31) and they were born 18 years later (P = 0.0001). Pre
treatment serum total cholesterol (TC) was similar in Alive and Dead (20.2 +/-
5.1 v 21.3 +/- 4.4 mmol/l, P = 0.52) but on-treatment TC was lower in Alive than
Dead (8.1 +/- 2.8 v 14.5 +/- 6.0 mmol/l, P = 0.0001) and CV adverse events were
far less frequent (eg aortic stenosis, 33% v 77%, P = 0.02). CONCLUSIONS: The
lower on-treatment TC and fewer CV adverse events in FH homozygotes still living
reflect advances in apheresis and drug therapy since the 1990s. Further
improvements in prognosis can be expected with the impending introduction of
novel lipid-lowering agents.
PMID- 26433115
TI - Elevated miR-155 expression induces immunosuppression via CD39(+) regulatory T
cells in sepsis patient.
AB - BACKGROUND: An altered microRNA profile exists in many infectious diseases,
including sepsis. CD39(+) regulatory T-cells (Tregs) have a remarkable
immunosuppressive effect and play an important role in the regulation of immune
balance in sepsis. However, the correlation between microRNA changes and the
ratio of CD39(+) Tregs in sepsis patients has not yet been reported. The altered
microRNA expression profile in sepsis patients was analyzed in this study.
Moreover, the correlation between microRNAs and disease severity and prognosis
was investigated. Furthermore, the correlation between microRNAs and the
percentage of peripheral blood CD39(+) Tregs was investigated and further
verified in an animal model. METHODS: Sixty sepsis patients and 30 healthy
controls were included. The difference in microRNA expression was investigated by
microRNA microarray and was further confirmed by real-time quantitative PCR. The
correlations between microRNA changes and the Sepsis-related Organ Failure
Assessment (SOFA) score, severity of sepsis, and survival were analyzed. The
percentage CD39(+) Tregs in the peripheral blood of sepsis patients was measured
by flow cytometry. The correlation between microRNAs and the percentage CD39(+)
Tregs was analyzed and further confirmed in a mouse sepsis model. RESULTS:
Compared to healthy controls, sepsis patients exhibited a significantly elevated
microRNA-155 (miR-155) level (p < 0.05), which was positively related to a higher
SOFA score (r = 0.641, p < 0.05) and a greater severity of sepsis. The area under
the receiver operating characteristic curve of miR-155 used for the prediction of
28-day survival was 0.763, with a cut-off point of 2.47. Patients with a miR-155
level >2.47 had a lower 28-day survival (p < 0.05). The miR-155 level of patients
was proportional to the percentage of CD39(+) Tregs (r = 0.637, p < 0.05). After
transfection with miR-155 inhibitor, the ratio of CD39(+) Tregs in mice with
sepsis was significantly reduced (p < 0.05). CONCLUSIONS: A higher level of miR
155 indicated a more severe condition and poorer prognosis in sepsis patients.
The possible underlying mechanism could be that miR-155 induces an increased
percentage of CD39(+) Tregs and thus immunosuppression.
PMID- 26433116
TI - Anxiety and depression among out-of-hospital cardiac arrest survivors.
AB - AIM: Survivors of out-of-hospital cardiac arrest (OHCA) may experience
psychological distress but the actual prevalence is unknown. The aim of this
study was to investigate anxiety and depression within a large cohort of OHCA
survivors. METHODS: OHCA-survivors randomized to targeted temperature of 33
degrees C or 36 degrees C within the Target Temperature Management trial (TTM
trial) attended a follow-up after 6 months that included the questionnaire
Hospital Anxiety and Depression Scale (HADS). A control group with ST-elevation
myocardial infarction (STEMI) completed the same follow-up. Correlations to
variables assumed to be associated with anxiety and depression in OHCA-survivors
were tested. RESULTS: At follow-up 278 OHCA-survivors and 119 STEMI-controls
completed the HADS where 24% of OHCA-survivors (28% in 33 degrees C group/22% in
36 degrees C group, p=0.83) and 19% of the STEMI-controls reported symptoms of
anxiety (OR 1.32; 95% CI (0.78-2.25), p=0.30). Depressive symptoms were reported
by 13% of OHCA-survivors (equal in both intervention groups, p=0.96) and 8% of
STEMI-controls (OR 1.76; 95% CI (0.82-3.79), p=0.15). Anxiety and depression
among OHCA-survivors correlated to Health-Related Quality-of-Life, and
subjectively reported cognitive deterioration by patient or observer. In
addition, depression was associated with a poor neurological outcome. CONCLUSION:
One fourth of OHCA-survivors reported symptoms of anxiety and/or depression at 6
months which was similar to STEMI-controls and previous normative data.
Subjective cognitive problems were associated with an increased risk for
psychological distress. Since psychological distress affects long-term prognosis
of cardiac patients in general it should be addressed during follow-up of
survivors with OHCA due to a cardiac cause. ClinicalTrials.gov
NCT01020916/NCT01946932.
PMID- 26433117
TI - Electronic learning in advanced resuscitation training: The perspective of the
candidate.
AB - BACKGROUND: Studies have shown that blended approaches combining e-learning with
face-to-face training reduces costs whilst maintaining similar learning outcomes.
The preferences in learning approach for healthcare providers to this new style
of learning have not been comprehensively studied. The aim of this study is to
evaluate the acceptability of blended learning to advanced resuscitation
training. METHODS: Participants taking part in the traditional and blended
electronic advanced life support (e-ALS) courses were invited to complete a
written evaluation of the course. Participants' views were captured on a 6-point
Likert scale and in free text written comments covering the content, delivery and
organisation of the course. Proportional-odds cumulative logit models were used
to compare quantitative responses. Thematic analysis was used to synthesise
qualitative feedback. RESULTS: 2848 participants from 31 course centres took part
in the study (2008-2010). Candidates consistently scored content delivered face
to-face over the same content delivered over the e-learning platform. Candidates
valued practical hands on training which included simulation highly. Within the e
ALS group, a common theme was a feeling of "time pressure" and they "preferred
the face-to-face teaching". However, others felt that e-ALS "suited their
learning style", was "good for those recertifying", and allowed candidates to
"use the learning materials at their own pace". CONCLUSIONS: The e-ALS course was
well received by most, but not all participants. The majority felt the e-learning
module was beneficial. There was universal agreement that the face-to-face
training was invaluable. Individual learning styles of the candidates affected
their reaction to the course materials.
PMID- 26433118
TI - Time to identify cardiac arrest and provide dispatch-assisted cardio-pulmonary
resuscitation in a criteria-based dispatch system.
AB - INTRODUCTION: Dispatch-assisted cardiopulmonary resuscitation (DA-CPR) plays a
key role in out-of-hospital cardiac arrests. We sought to measure dispatchers'
performances in a criteria-based system in recognizing cardiac arrest and
delivering DA-CPR. Our secondary purpose was to identify the factors that
hampered dispatchers' identification of cardiac arrests, the factors that
prevented them from proposing DA-CPR, and the factors that prevented bystanders
from performing CPR. METHODS AND RESULTS: We reviewed dispatch recordings for
1254 out-of-hospital cardiac arrests occurring between January 1, 2011 and
December 31, 2013. Dispatchers correctly identified cardiac arrests in 71% of the
reviewed cases and 84% of the cases in which they were able to assess for patient
consciousness and breathing. The median time to recognition of the arrest was
60s. The median time to start chest compression was 220s. CONCLUSIONS: This study
demonstrates that performances from a criteria-based dispatch system can be
similar to those from a medical-priority dispatch system regarding out-of
hospital cardiac arrest (OHCA) time recognition and DA-CPR delivery. Agonal
breathing recognition remains the weakest link in this sensitive task in both
systems. It is of prime importance that all dispatch centers tend not only to
implement DA-CPR but also to have tools to help them reach this objective, as
today it should be mandatory to offer this service to the community. In order to
improve benchmarking opportunities, we completed previously proposed performance
standards as propositions.
PMID- 26433119
TI - Combined omega-3 fatty acids, aerobic exercise and cognitive stimulation prevents
decline in gray matter volume of the frontal, parietal and cingulate cortex in
patients with mild cognitive impairment.
AB - Previous studies in older adults suggested beneficial effects of omega-3 fatty
acid (FA) supplementation, aerobic exercise, or cognitive stimulation on brain
structure and function. However, combined effects of these interventions in
patients suffering from mild cognitive impairment (MCI) are unknown. Using a
randomized interventional design, we evaluated the effect of combined omega-3 FA
supplementation, aerobic exercise and cognitive stimulation (target intervention)
versus omega-3 FA supplementation and non-aerobic exercise (control intervention)
on cognitive function and gray matter volume in patients with MCI. Moreover, we
analyzed potential vascular, metabolic or inflammatory mechanisms underlying
these effects. Twenty-two MCI patients (8 females; 60-80years) successfully
completed six months of omega-3 FA intake, aerobic cycling training and cognitive
stimulation (n=13) or omega-3 FA intake and non-aerobic stretching and toning
(n=9). Before and after the interventions, cognitive performance, magnetic
resonance imaging of the brain at 3T (n=20), intima-media thickness of the
internal carotid artery and serum markers of glucose control, lipid and B-vitamin
metabolism, and inflammation were assessed. Intervention-related changes in gray
matter volume of Alzheimer's disease (AD)-related brain regions, i.e., frontal,
parietal, temporal and cingulate cortex were examined using voxel-based
morphometry of high resolution T1-weighted images. After the intervention period,
significant differences emerged in brain structure between groups: Gray matter
volume decreased in the frontal, parietal and cingulate cortex of patients in the
control intervention, while gray matter volume in these areas was preserved or
even increased after the target intervention. Decreases in homocysteine levels in
the target intervention group were associated with increases in gray matter
volume in the middle frontal cortex (p=0.010). No significant differences in
cognitive performance or other vascular, metabolic and inflammatory parameters
were observed between groups. This pilot study provides preliminary evidence that
omega-3 FA intake combined with aerobic exercise and cognitive stimulation
prevents atrophy in AD-related brain regions in MCI patients, compared to omega-3
FA intake plus the control condition of stretching and toning. These promising
findings should now be validated in a larger interventional trial.
PMID- 26433120
TI - Dissociating temporal attention from spatial attention and motor response
preparation: A high-density EEG study.
AB - Engagement of various forms of attention and response preparation determines
behavioral performance during stimulus-response tasks. Many studies explored the
respective properties and neural signatures of each of these processes. However,
very few experiments were conceived to explore their interaction. In the present
work we used an auditory target detection task during which both temporal
attention on the one side, and spatial attention and motor response preparation
on the other side could be explicitly cued. Both cueing effects speeded response
times, and showed strictly additive effects. Target ERP analysis revealed
modulations of N1 and P3 responses by these two forms of cueing. Cue-target
interval analysis revealed two main effects paralleling behavior. First, a
typical contingent negative variation (CNV), induced by the cue and resolved
immediately after target onset, was found larger for temporal attention cueing
than for spatial and motor response cueing. Second, a posterior and late cue-P3
complex showed the reverse profile. Analyses of lateralized readiness potentials
(LRP) revealed both patterns of motor response inhibition and activation. Taken
together these results help to clarify and disentangle the respective effects of
temporal attention on the one hand, and of the combination of spatial attention
and motor response preparation on the other hand on brain activity and behavior.
PMID- 26433121
TI - Fragrance sensitisers: Is inhalation an allergy risk?
AB - It is well established that some fragrance substances have the potential to cause
skin sensitisation associated with the development of allergic contact dermatitis
(ACD). Fragrances are invariably relatively volatile leading to the consideration
that inhalation of fragrances might be a relevant route for either the induction
of allergic sensitisation or the elicitation of allergic reactions. Moreover,
there has been increasing recognition that allergic sensitisation of the
respiratory tract can be induced by topical exposure to certain chemical
allergens. Here the central question addressed is whether inhalation exposure to
fragrance allergens has the potential to cause skin and/or respiratory
sensitisation via the respiratory tract, or elicit allergic symptoms in those
already sensitised. In addressing those questions, the underlying immunobiology
of skin and respiratory sensitisation to chemicals has been reviewed briefly, and
the relevant experimental and clinical evidence considered. The essential
mechanistic differences between skin and respiratory allergy appear consistent
with other sources of information, including the phenomenon of ACD that can arise
from topical exposure to airborne allergens, but in the absence of accompanying
respiratory effects. The conclusion is that, in contrast to topical exposure
(including topical exposure to airborne material), inhalation of fragrance
sensitisers does not represent a health risk with respect to allergy.
PMID- 26433122
TI - Creation of a new longitudinal corpus of clinical narratives.
AB - The 2014 i2b2/UTHealth Natural Language Processing (NLP) shared task featured a
new longitudinal corpus of 1304 records representing 296 diabetic patients. The
corpus contains three cohorts: patients who have a diagnosis of coronary artery
disease (CAD) in their first record, and continue to have it in subsequent
records; patients who do not have a diagnosis of CAD in the first record, but
develop it by the last record; patients who do not have a diagnosis of CAD in any
record. This paper details the process used to select records for this corpus and
provides an overview of novel research uses for this corpus. This corpus is the
only annotated corpus of longitudinal clinical narratives currently available for
research to the general research community.
PMID- 26433123
TI - p53-dependent and p53-independent anticancer activity of a new indole derivative
in human osteosarcoma cells.
AB - Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring
most frequently in children and adolescents. The mechanism of formation and
development of OS have been studied for a long time. Tumor suppressor pathway
governed by p53 gene are known to be involved in the pathogenesis of
osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major
predictor of failure to respond to chemotherapy in various human cancers. In
previous studies, we described the activity of a new indole derivative,
NSC743420, belonging to the tubulin inhibitors family, capable to induce
apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell
lines. However, this molecule has never been tested on OS cell line. Here we
address the activity of NSC743420 by examine whether differences in the p53
status could influence its effects on cell proliferation and death of OS cells.
In particular, we compared the effect of the tested molecule on p53-wild type and
p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our
results demonstrated that NSC743420 reduces OS cell proliferation by p53
dependent and p53-independent mechanisms. In particular, the molecule induces
proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while
it brings a cytostatic and differentiating effect in U2OS cells, characterized by
the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity.
PMID- 26433124
TI - Implication of a galactomannan-binding GH2 beta-mannosidase in mannan utilization
by Caldicellulosiruptor bescii.
AB - Many glycoside hydrolases involved in deconstruction of cellulose and xylan from
the excellent plant cell wall polysaccharides-degrader Caldicellulosiruptor
bescii have been cloned and analyzed. However, far less is known about the
enzymatic breakdown of mannan, an important component of hemicellulose. We herein
cloned, expressed and purified the first beta-mannosidase CbMan2A from C. bescii.
CbMan2A is thermophilic, with an optimal temperature of 80 degrees C. CbMan2A
hydrolyzes mannooligosaccharides with degrees of polymerization from 2 to 6
mainly into mannose and shows strong synergy with CbMan5A, an endo-mannanase from
the same bacterium, in releasing mannose from beta-1,4-mannan. Thus CbMan2A forms
the missing link in enzymatic conversion of mannan into the ready-to-use mannose
by C. bescii. Based on these observations, a model illustrating how CbMan2A may
assist C. bescii in mannan utilization is presented. In addition, CbMan2A
appeared to bind to insoluble galactomannan in a pH-dependent fashion. Although
the relation of this feature to mannan utilization remains elusive, CbMan2A
represents an excellent model for investigation of the binding of GH2 beta
mannosidases to galactomannan.
PMID- 26433126
TI - Importance of corneal saturation time with riboflavin prior to collagen cross
linking.
PMID- 26433127
TI - A negative feedback loop between miR-200b and the nuclear factor-kappaB pathway
via IKBKB/IKK-beta in breast cancer cells.
AB - MicroRNAs (miRNAs) act as important post-transcriptional regulators of gene
expression in diverse signalling pathways. However, the relationship between miR
200b and the nuclear factor-kappaB (NF-kappaB) signalling pathway remains poorly
understood in breast cancer cells. In the current study, we show that IKBKB is a
direct target of miR-200b, and that miR-200b downregulates IKBKB expression via
directly binding to its 3'-UTR. miR-200b inhibits IkappaBalpha phosphorylation,
nuclear p50/p65 expression, NF-kappaB-binding activity, and the translocation of
p65 to the nucleus. In addition, miR-200b also suppresses tumour necrosis factor
(TNF)-alpha-induced NF-kappaB activation and the expression of NF-kappaB target
genes. Importantly, IKBKB overexpression attenuates the inhibitory roles of miR
200b in NF-kappaB expression, NF-kappaB-binding activity, and the nuclear
translocation of p65. We also show that NF-kappaB p65 knockdown reduces the
binding of NF-kappaB to the miR-200b promoter and miR-200b promoter activity.
Furthermore, p65 knockdown or inhibition of IkappaBalpha phosphorylation
suppresses miR-200b expression. Finally, functional studies show that IKBKB
overexpression can restore the cell growth and migration that are suppressed by
miR-200b. In conclusion, our results demonstrate that miR-200b, a transcriptional
target of NF-kappaB, suppresses breast cancer cell growth and migration, and NF
kappaB activation, through downregulation of IKBKB, indicating that miR-200b has
potential as a therapeutic target in breast cancer patients.
PMID- 26433125
TI - Exploring the role of polymer structure on intracellular nucleic acid delivery
via polymeric nanoparticles.
AB - Intracellular nucleic acid delivery has the potential to treat many genetically
based diseases, however, gene delivery safety and efficacy remains a challenging
obstacle. One promising approach is the use of polymers to form polymeric
nanoparticles with nucleic acids that have led to exciting advances in non-viral
gene delivery. Understanding the successes and failures of gene delivery polymers
and structures is the key to engineering optimal polymers for gene delivery in
the future. This article discusses the polymer structural features that enable
effective intracellular delivery of DNA and RNA, including protection of nucleic
acid cargo, cellular uptake, endosomal escape, vector unpacking, and delivery to
the intracellular site of activity. The chemical properties that aid in each step
of intracellular nucleic acid delivery are described and specific structures of
note are highlighted. Understanding the chemical design parameters of polymeric
nucleic acid delivery nanoparticles is important to achieving the goal of safe
and effective non-viral genetic nanomedicine.
PMID- 26433128
TI - Enhancement of solvent tolerance in Pseudomonas sp. BCNU 106 with trehalose.
AB - As the solvent hyper-resistant Pseudomonas sp. BCNU 106 experiences limited
growth with solvents, a strategy is therefore needed to allow better growth to
broaden its performance in biotechnological applications. Pseudomonas sp. BCNU
106 was cultivated in a medium supplemented with 0.05 mol l(-1) trehalose, and
the cell survival was observed during subsequent growth with 1% (v/v) toluene.
Exogenously added trehalose was transported into the cells and conferred
protection against toluene stress. BCNU 106 grown in the presence of exogenous
trehalose showed higher solvent tolerance, it can thus have more potential for
biotransformation and biodegradation. SIGNIFICANCE AND IMPACT OF THE STUDY: This
study shows that exogenously supplemented trehalose confers protection against
toluene stress and enhances the bacterial cell growth in the presence of toluene.
This is of importance to the mass cultivation of solvent-tolerant bacteria, where
some of the growth-related limitations of solvent-tolerant bacteria can be
overcome, and their performance in biotechnological applications for
biotransformation and biodegradation broadened.
PMID- 26433130
TI - Outcomes from community-based diabetic eye disease screening: a 3-year review.
PMID- 26433129
TI - GCKR and PPP1R3B identified as genome-wide significant loci for plasma lactate:
the Atherosclerosis Risk in Communities (ARIC) study.
AB - AIM: To investigate the genetic influence of circulating lactate level, a marker
of oxidative capacity associated with diabetes. METHODS: We conducted a genome
wide association study of log-transformed plasma lactate levels in 6901 European
American participants in the Atherosclerosis Risk in Communities study. For
regions that achieved genome-wide significance in European-American participants,
we conducted candidate region analysis in African-American subjects and tested
for interaction between metformin use and the index single nucleotide
polymorphisms for plasma lactate in European-American subjects. RESULTS: The
genome-wide association study in European-American subjects identified two genome
wide significant loci, GCKR (rs1260326, T allele beta=0.08; P=1.8*10(-47) ) and
PPP1R3B/LOC157273 (rs9987289, A allele beta=0.06; P=1.6*10(-9) ). The index
single nucleotide polymorphisms in these two loci explain 3.3% of the variance in
log-transformed plasma lactate levels among the European-American subjects. In
the African-American subjects, based on a region-significant threshold, the index
single nucleotide polymorphism at GCKR was associated with plasma lactate but
that at PPP1R3B/LOC157273 was not. Metformin use appeared to strengthen the
association between the index single nucleotide polymorphism at PPP1R3B/LOC157273
and plasma lactate in European-American subjects (P for interaction=0.01).
CONCLUSIONS: We identified GCKR and PPP1R3B/LOC157273 as two genome-wide
significant loci of plasma lactate. Both loci are associated with other diabetes
related phenotypes. These findings increase our understanding of the genetic
control of lactate metabolism.
PMID- 26433131
TI - Improved simultaneous estimation of tracer kinetic models with artificial immune
network based optimization method.
AB - Tracer kinetic modeling (TKM) is a promising quantitative method for
physiological and biochemical processes in vivo. In this paper, we investigated
the applications of an immune-inspired method to better address the issues of
Simultaneous Estimation (SIME) of TKM with multimodal optimization. Experiments
of dynamic FDG PET imaging experiments and simulation studies were carried out.
The proposed artificial immune network (TKM_AIN) shows more scalable and
effective when compared with the gradient-based Marquardt-Levenberg algorithm and
the scholastic-based simulated annealing method.
PMID- 26433132
TI - Pseudotumoral presentation of fungating mycetoma caused by Phaeoacremonium fuscum
in a renal transplant patient.
AB - Eumycetoma is an unusual infection in immunocompromised patients outside the
tropics, caused by a variety of fungal pathogens. We describe the case of a 51
year-old renal transplant recipient who presented with a large pseudotumoral foot
lesion necessitating complete surgical excision of the lesion. Cultures and
molecular diagnosis confirmed Phaeoacremonium fuscum. This is the first case, to
our knowledge, of fungating mycetoma caused by this fungal species in a solid
organ transplant recipient.
PMID- 26433133
TI - Does exposure to hyperglycaemia in utero increase the risk of obesity and
diabetes in the offspring?
PMID- 26433134
TI - Physicians' Reflections on Death and Dying on Completion of a Palliative Medicine
Fellowship.
AB - CONTEXT: Patient and family dissatisfaction may result when they are not
satisfied with the physician/patient interaction, although the physician may feel
he/she worked hard to provide information to the patient and family. New
approaches to visual analysis can (1) identify significant insights from
physicians' personal and clinical experiences in providing compassionate
palliative care and end-of-life care and (2) provide an effective and practical
vehicle for communicating with patients, their families, and other professional
caregivers. OBJECTIVES: To elucidate palliative physicians' core experiences with
their patients' dying and death. METHODS: A qualitative visual analysis was
conducted on 75 images created by physicians completing a one year palliative
medicine fellowship. These images are part of a larger personal reflections
narratives database of images, text, and auditory projects prepared by students,
interns, and fellows completing training in palliative care at a large hospice
provider. Participation in the personal reflections project is a required part of
the training program, with the goal of blending clinical competencies with lived
experiences of caring for the dying. RESULTS: Two categories of visual metaphors
underlying the images were identified, with both expressing the relationship and
transitional dynamics of life and death: portraits (n = 30, 40%) and nature (n =
45, 60%). Conventional images representing anxiety, pain, or other dimensions of
suffering commonly associated with death and dying were virtually absent (n = 2,
0.03%). CONCLUSION: We propose the communication of positive, hopeful, even
peaceful perceptions of death and dying was likely the result of effective
personal and professional skills gained through physicians' clinical experiences
during the fellowship.
PMID- 26433135
TI - The Social Convoy for Family Caregivers Over the Course of Hospice.
AB - CONTEXT: Family caregivers play a central role in the care of those in hospice
care. Little is known about the social support networks for those providing this
day-to-day care without training. OBJECTIVES: The purpose of this study was to
explore changes in family and friend social networks among hospice caregivers
over the course of the hospice stay. METHODS: Data on social support networks
were collected as part of a multisite randomized controlled trial and analyzed
using structural equation modeling. RESULTS: A statistically significant decline
in the caregivers' family network subscale score was found over the four week
period during which they received hospice services, reflecting a possible
weakening of their family networks. CONCLUSION: This result illustrates the
potential importance of ongoing comprehensive assessment of caregiver networks
and attention to interventions that may assist in capitalizing on both the
quantity of support (numbers of individuals asked to help) and the quality of
social support (attending to issues of support burden).
PMID- 26433136
TI - ACROSCORE: a new and simple tool for the diagnosis of acromegaly, a rare and
underdiagnosed disease.
AB - OBJECTIVE: Acromegaly, a disease caused by GH/IGF-I hypersecretion, is associated
with a high mortality rate; early recognition is therefore necessary to ensure
successful treatment and to avoid comorbidities. We have created a symptom/sign
scoring tool (ACROSCORE) for physicians to use to identify acromegaly. DESIGN: To
compare cases of acromegaly diagnosed between 1990 and 2014 against a control
group affected by non-GH-secreting pituitary tumours to identify symptoms and
signs that are most discriminative for acromegaly. PATIENTS: Confirmed acromegaly
patients and patients affected by non-GH-secreting pituitary tumours.
MEASUREMENTS: In all patients, signs, symptoms and comorbidities were recorded
from medical records and collected using a specifically designed questionnaire.
RESULTS: A total of 194 acromegaly patients [115 women; mean (SD) age 47.2 (14.2)
years] and 243 patients affected by non-GH-secreting pituitary tumours [131
women; mean (SD) age 45.8 (15.8) years] were included. A strong association was
observed for type 2/secondary diabetes [odds ratio (OR) 3.7], hyperhidrosis (OR
6.1), thyroid hyperplasia (OR 13.9), colorectal polyps (OR 10.4), spaced teeth
(OR 25.4) and carpal tunnel syndrome (OR 4.3). Based on this information, a
multivariable logistic model was built and a 14-point scoring system developed. A
score of 0 excludes the risk of acromegaly [positive predictive value (PV(+)) =
0.6%]; scores 1-5 comprise a grey area; scores >5 indicate that a diagnosis of
acromegaly cannot be excluded (PV(+) = 46.1%). CONCLUSIONS: Once validated in
independent studies, ACROSCORE may represent a new tool for the clinical
screening of acromegaly that can be used by general practitioners and
nonendocrinology specialists.
PMID- 26433137
TI - UPLC-HRMS based metabolomics reveals the sphingolipids with long fatty chains and
olefinic bonds up-regulated in metabolic pathway for hypoxia preconditioning.
AB - Hypoxia preconditioning (HPC) could protect cells, tissues, organs and systems
from hypoxia injury, but the molecular mechanism still remained unclear. The
ultra-high performance liquid chromatography coupled high resolution mass
spectrometry (UPLC-HRMS) based metabolomics method was utilized to explore the
key endogenous metabolites and metabolic pathways related to HPC. Our results
clearly showed that the HPC mice model was established and refined, suggesting
that there were significant differences between the control group and 6 * HPC
group at the molecular levels. A serious of statistical analyses, including
univariate analysis and multivariate analysis, were performed by the Progenesis
QI software package and MetaboAnalyst web-server. The sphingolipid metabolic
pathways were noticed due to the low p-value and high pathway impact calculated
by the MetaboAnalyst and the pathways were altered under HPC condition.
Especially, the sphingolipid compound sphingomyelin, ceramide, glucosylceramide,
galactosylceramide and lactosylceramide were mapping in this metabolic pathway.
Interestingly, these sphingolipid metabolites with olefinic bond in the long
fatty chain were up-regulated, while those sphingolipids without olefinic bond
were down-regulated. The results indicated that C24:1-Cers played a critical role
in HPC and had potential in endogenous protective mechanism. Our data provided an
insight to further reveal the protection mechanism of HPC.
PMID- 26433138
TI - Relative hypoaldosteronism in a patient with Wolcott-Rallison syndrome.
AB - BACKGROUND: Wolcott-Rallison syndrome is an autosomal recessive, multisystem
disorder with onset of diabetes in the neonatal period or early infancy. CASE
REPORT: A 9-year-old girl with diabetes and growth failure from 2 months of age
presented with ketoacidosis and multiple organ failure. Evaluation for short
stature revealed epiphyseal dysplasia. A homozygous mutation in the EIF2AK3 gene
confirmed the clinical diagnosis of Wolcott-Rallison syndrome. She was euthyroid.
Biochemical evaluation for potential adrenal dysfunction because of persistently
elevated serum potassium (range 5.9-6.3 meq/l) and low serum sodium levels (range
128-130 meq/l) 2 weeks after resolution of ketoacidosis yielded normal findings
with respect to basal corticotropin (31 pg/ml) and cortisol (18.7 MUg/dl) levels.
Estimated GFR-Schwartz (36.9 ml/min/1.73 m(2) ) was consistent with stage 3
chronic renal failure. The transtubular potassium gradient was 1.39 (normal value
in hyperkalemic states: > 4.1). The plasma aldosterone (upright: 241.3 pmol/l)
was within normal ranges, and plasma renin [39 pg/ml (range 5.41-34.53 pg/ml)]
was slightly elevated. The patient was diagnosed as having relative
hypoaldosteronism and was started on a sodium-rich diet and low potassium.
Failure to respond to the dietary intervention prompted a trial of oral
fludrocortisone with subsequent normalization of electrolyte levels. CONCLUSIONS:
This is the first case report of Wolcott-Rallison syndrome complicated with
relative hypoaldosteronism. Further research is needed to probe the causal
inference of relative hypoaldosteronism with chronic renal failure in patients
with Wolcott-Rallison syndrome.
PMID- 26433139
TI - Longitudinal circulating concentrations of long-chain polyunsaturated fatty acids
in the third trimester of pregnancy in gestational diabetes.
AB - AIM: Gestational diabetes mellitus is a common complication of pregnancy. Long
chain polyunsaturated fatty acids (LCPUFA) are essential for fetal
neurodevelopment. Docosahexaenoic acid (DHA) is the predominant n-3 LCPUFA in the
brain and retina. Circulating absolute concentrations of total n-3 and n-6
LCPUFAs rise during normal pregnancy. It remains unclear whether gestational
diabetes may affect the normal rise in circulating concentrations of LCPUFAs in
the third trimester of pregnancy - a period of rapid fetal neurodevelopment. This
study aimed to address this question. METHODS: In a prospective singleton
pregnancy cohort, fatty acids in fasting plasma total lipids were measured at 24
28 and 32-35 weeks of gestation in women with (n = 24) and without gestational
diabetes mellitus (n = 116). Fatty acid desaturase activity indices were
estimated by relevant product-to-precursor fatty acid ratios. Dietary nutrient
intakes were estimated by a food frequency questionnaire. RESULTS: Plasma
absolute concentrations of total n-6 LCPUFAs rose significantly between 24-28 and
32-35 weeks of gestation in women with or without gestational diabetes, whereas
total n-3 LCPUFAs and DHA concentrations rose significantly only in women without
gestational diabetes (all P < 0.01). Delta-5 desaturase indices (20:4n-6/20:3n-6)
were similar, but delta-6 desaturase indices (18:3n-6/18:2n-6) were significantly
lower in women with gestational diabetes at 32-35 weeks of gestation. Dietary
intakes of all fatty acids were comparable. CONCLUSION: The normal rise in
circulating absolute concentrations of DHA and total n-3 LCPUFAs in the third
trimester of pregnancy may be compromised in gestational diabetes, probably due
to impaired synthesis or mobilization rather than dietary intake difference.
PMID- 26433140
TI - Impact of Reduced Glomerular Filtration Rate and Proteinuria on Overall Survival
of Patients with Renal Cancer.
AB - PURPOSE: Although it is commonly staged according to glomerular filtration rate,
an international work group recommended classifying chronic kidney disease by
cause, glomerular filtration rate and albuminuria. Data on nonsurgical patients
with chronic kidney disease indicate proteinuria to be an independent predictor
of renal function decrease and mortality. We evaluated whether preoperative
proteinuria impacted survival in patients undergoing nephrectomy. MATERIALS AND
METHODS: An institutional registry was queried for information regarding
preoperative creatinine/glomerular filtration rate and urinalysis in 900
patients, including 362 and 538 treated with partial and radical nephrectomy,
respectively. Patients were grouped according to glomerular filtration rate level
(G1 to G5), proteinuria level (A1 to A3) and chronic kidney disease risk
classification (low to very high). Kaplan-Meier and Cox proportional hazards
analyses of overall survival were performed. RESULTS: The preoperative glomerular
filtration rate was less than 60 ml/minute/1.73 m(2) in 30% of patients (median
73, IQR 56-91) and 20% of patients had baseline proteinuria. According to the
KDIGO (Kidney Disease Improving Global Outcomes) classification 23% of patients
were at moderately increased, 11% were at high and 8% were at very high risk for
chronic kidney disease progression. Kaplan-Meier analysis revealed that the
preoperative glomerular filtration rate, proteinuria and chronic kidney disease
risk group were associated with poor overall survival. In Cox proportional hazard
models accounting for age, gender, race, tumor size, clinical stage and surgery
type the glomerular filtration rate, proteinuria and chronic kidney disease risk
group were highly significant predictors of overall survival (p <0.0001).
CONCLUSIONS: Preoperative proteinuria is a significant predictor of overall
survival in patients who undergo nephrectomy. Classification according to
preoperative glomerular filtration rate and proteinuria more accurately predicts
survival than using the glomerular filtration rate alone after accounting for
cancer stage. This information supports routine evaluation of proteinuria in
patients with kidney cancer.
PMID- 26433141
TI - The introduction of the meningococcal B (MenB) vaccine (Bexsero(r)) into the
national infant immunisation programme--New challenges for public health.
AB - The United Kingdom is the first country to introduce Bexsero((r)) (GSK
Biologicals), a multicomponent, protein-based vaccine against meningococcal group
B (MenB), into the national infant immunisation programme. This vaccine is like
no other licensed vaccine and poses a number of implementation and surveillance
challenges in England. From 01 September 2015, UK infants were offered a reduced
two dose primary immunisation schedule at 2 and 4 months followed by a booster at
12 months. Because of high rates of fever post-vaccination, parents were advised
to give their infants three doses of prophylactic paracetamol, with the first
dose given as soon as possible after the primary MenB vaccination dose. Since the
vaccine only protects against 73-88% of MenB strains causing invasive disease in
England, clinical isolates and PCR-positive samples will require extensive
characterisation by the Meningococcal Reference Unit (MRU) at Public Health
England (PHE) in order to monitor vaccine effectiveness and identify potential
vaccine failures. PHE is also conducting detailed clinical and epidemiological
surveillance to assess the impact of the MenB immunisation programme on the
morbidity and mortality associated with invasive meningococcal disease in infants
and young children.
PMID- 26433142
TI - Whole spine imaging is justified in tuberculous spondylodiscitis but not pyogenic
spondylodiscitis.
PMID- 26433143
TI - Specialist enemies, generalist weapons and the potential spread of exotic
pathogens: malaria parasites in a highly invasive bird.
AB - Pathogens can influence the success of invaders. The Enemy Release Hypothesis
predicts invaders encounter reduced pathogen abundance and diversity, while the
Novel Weapons Hypothesis predicts invaders carry novel pathogens that spill over
to competitors. We tested these hypotheses using avian malaria (haemosporidian)
infections in the invasive myna (Acridotheres tristis), which was introduced to
southeastern Australia from India and was secondarily expanded to the eastern
Australian coast. Mynas and native Australian birds were screened in the
secondary introduction range for haemosporidians (Plasmodium and Haemoproteus
spp.) and results were combined with published data from the myna's primary
introduction and native ranges. We compared malaria prevalence and diversity
across myna populations to test for Enemy Release and used phylogeographic
analyses to test for exotic strains acting as Novel Weapons. Introduced mynas
carried significantly lower parasite diversity than native mynas and
significantly lower Haemoproteus prevalence than native Australian birds. Despite
commonly infecting native species that directly co-occur with mynas, Haemoproteus
spp. were only recorded in introduced mynas in the primary introduction range and
were apparently lost during secondary expansion. In contrast, Plasmodium
infections were common in all ranges and prevalence was significantly higher in
both introduced and native mynas than in native Australian birds. Introduced
mynas carried several exotic Plasmodium lineages that were shared with native
mynas, some of which also infected native Australian birds and two of which are
highly invasive in other bioregions. Our results suggest that introduced mynas
may benefit through escape from Haemoproteus spp. while acting as important
reservoirs for Plasmodium spp., some of which are known exotic lineages.
PMID- 26433144
TI - l-Scoulerine attenuates behavioural changes induced by methamphetamine in
zebrafish and mice.
AB - Methamphetamine (METH), a substance with a high potential for abuse and
addiction, is a serious worldwide public health problem. METH addicts often show
extreme paranoia, anxiety, and depression. Thus, there is no effective medication
for the treatment of METH-induced abnormalities. In the present study, we
investigated the effects of l-Scoulerine (l-SLR), a tetrahydroprotoberberine
(THPBS) alkaloid, on METH-induced anxiety-like behaviour in zebrafish and METH
induced addictive behavior in mice. In the novel tank test, acute administration
of METH (2 mg/L) induced a significant decrease in the number of total vertical
transitions and time spent in the upper zone. Moreover, METH produced significant
avoidance behaviour showing increased swimming time in the central area and high
speed movement in the mirror area in the mirror stimulation test; these anxiety
like changes were attenuated by l-SLR. Chronic administration of METH (2 mg/kg)
produced a steady increase in locomotor activity and conditioned place preference
in mice. l-SLR (5 mg/kg) failed to reduce acute METH-induced hyperlocomotion, but
attenuated chronic METH-induced behavioural sensitization and significantly
blocked the expression of conditioned place preference induced by METH in mice.
The present study suggests that l-SLR may be a promising agent for the treatment
of addiction and anxiety induced by METH.
PMID- 26433145
TI - Interpersonal stroking touch is targeted to C tactile afferent activation.
AB - C tactile fibers are a specialized group of fibers innervating the non-glabrous
skin that are tuned to light gentle stroking applied with velocities between 1
and 10 cm/s. Those fibers add to the sensation of interpersonal caressing and
pleasant touch. It is unclear whether people spontaneously apply touch that is
tuned to optimally activate those fibers. This was investigated in three studies.
In study one, 45 participants (21.8 +/- 2.3 years, 24 women) were asked to stroke
an artificial arm. In study two, 32 participants (28.3 +/- 8.7 years, 16 women)
were asked to stroke their partner. In study three, 11 parents (29.4 +/- 5.7
years, 6 women) were asked to stroke their babies. Stroking velocity was tracked
in all conditions. Stroking velocities were significantly slower in the partner
touch and baby touch condition than in the artificial arm condition and all of
the participants stroking their partner or baby used velocities that can activate
C tactile fibers. We conclude that human social stroking is optimized for C
tactile stimulation.
PMID- 26433146
TI - Brain-derived neurotrophic factor into adult neocortex strengthens a taste
aversion memory.
AB - Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein
critically involved in regulating long-term memory related mechanisms. Previous
studies from our group in the insular cortex (IC), a brain structure of the
temporal lobe implicated in acquisition, consolidation and retention of
conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA
consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate
the enhancement of memory. However, whether BDNF into neocortex is able to
enhance aversive memories remains unexplored. In the present work, we
administrated BDNF in a concentration capable of inducing in vivo neocortical
LTP, into the IC immediately after CTA acquisition in two different conditions: a
"strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and
a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion
of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor
dependent manner. The present data suggest that BDNF into the adult insular
cortex is sufficient to increase an aversive memory-trace.
PMID- 26433148
TI - Exocrine pancreas ER stress is differentially induced by different fatty acids.
AB - Exocrine pancreas acinar cells have a highly developed endoplasmic reticulum
(ER), accommodating their high protein production rate. Overload of dietary fat
(typical to obesity) is a recognized risk factor in pancreatitis and pancreatic
cancer. Dietary fat, especially saturated fat, has been suggested by others and
us to induce an acinar lipotoxic effect. The effect of different dietary fatty
acids on the ER stress response is unknown. We studied the effect of acute (24h)
challenge with different fatty acids (saturated, mono and poly-unsaturated) at
different concentrations (between 200 and 500uM, typical to normal and obese
states, respectively), testing fat accumulation, ER stress indicators, X-box
binding protein 1 (Xbp1) splicing and nuclear translocation, as well as unfolded
protein response (UPR) transcripts and protein levels using exocrine pancreas
acinar AR42J and primary cells. Acute exposure of AR42J cells to different fatty
acids caused increased accumulation of triglycerides, dependent on the type of
fat. Different FAs had different effects on ER stress: most notably, saturated
palmitic acid significantly affected the UPR response, as demonstrated by altered
Xbp1 splicing, elevation in transcript levels of UPR (Xbp, CHOP, Bip) and immune
factors (Tnfalpha, Tgfbeta), and enhanced Xbp1 protein levels and Xbp1 time
dependent nuclear translocation. Poly-unsaturated FAs caused milder elevation of
ER stress markers, while mono-unsaturated oleic acid attenuated the ER stress
response. Thus, various fatty acids differentially affect acinar cell fat
accumulation and, apart from oleic acid, induce ER stress. The differential
effect of the various fatty acids could have potential nutritional and
therapeutic implications.
PMID- 26433147
TI - Synthesis of new steroidal imidazo [1,2-a] pyridines: DNA binding studies,
cleavage activity and in vitro cytotoxicity.
AB - A one-pot strategy for the catalytic synthesis of series of new 5alpha-cholestan
6-spiro-5'-phenylamino-2H-imidazo [1',2'-a] pyridines (4-14) has been
investigated. The synthesized products were obtained in good yields (85-90%) and
the protocol uses Multi-component Reaction (MCR) involving steroidal ketones, 2
aminopyridines, isocyanides and propylphosphonic anhydride ((r)T3P) as a
catalyst. After characterization by spectral and analytical data, the interaction
studies of compounds (4-6) with DNA were studied by UV-vis, fluorescence
spectroscopy, gel electrophoresis and molecular docking. The compounds bind to
DNA preferentially through electrostatic and hydrophobic interactions with Kb;
2.35*10(4), 3.71*10(4) and 3.24*10(4) M(-1), respectively, indicating the higher
binding affinity of compound 5 towards DNA. Gel electrophoresis showed the
concentration dependent cleavage activity of compounds 4-6 with DNA. Molecular
docking studies suggested that compounds bind through minor groove to DNA. The 3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay depicted
promising anti-proliferative activity of compound 4-9 against different given
cancer cells. In Western blotting, the expressions of relevant apoptotic markers
depicted an apoptosis by steroidal imidazopyridines in A549 cells. Annexin V
FITC/PI staining data indicated that compounds could effectively induce apoptosis
in A549 cells in a dose-dependent manner. FACS analysis shows that the compound 6
bring about cell cycle arrest at 2.62 MUM concentration.
PMID- 26433149
TI - The chemical properties and microbial community characterization of the
thermophilic microaerobic pretreatment process.
AB - Thermophilic microaerobic pretreatment (TMP) was recently reported as an
efficient pretreatment method of anaerobic digestion (AD). In this study, the
chemical properties and microbial community were characterized to reveal how TMP
working. Compared with thermophilic treatment under anaerobic condition (TMP0),
cellulase activity obviously improved under microaerobic condition (TMP1), which
was 10.9-49.0% higher than that of TMP0. Reducing sugar, SCOD and VFAs
concentrations of TMP1 were 2.6-8.9%, 1.8-4.8% and 13.8-24% higher than those of
TMP0, respectively. TMP gave obvious rise to phylum Firmicutes, which associated
with extracellular enzymes production. The proportion of class Bacilli (belongs
to phylum Firmicutes and mainly acts during hydrolysis) in TMP1 was 124.89%
higher than that of TMP0, which reflected the greater hydrolytic ability under
microaerobic condition. The improved abundance of phylum Firmicutes (especially
class Bacilli, order Bacillales) under microaerobic condition could be the
fundamental reason for the improved AD performance of thermophilic microaerobic
pretreated corn straw.
PMID- 26433150
TI - End-product inhibition and acidification limit biowaste fermentation efficiency.
AB - Converting waste to resource may mitigate environmental pollution and global
resource limitation. The platform chemical lactic acid can be produced from
biowaste and its liquid fraction after solid-liquid separation. A fermentation
step for lactic acid production prior to the conversion of biowaste to methane
and organic fertilizer would increase the biowaste's value. Despite the huge
potential and promising results of the treatment procedure, the reasons for
efficiency loss observed previously need to be addressed in order to pave the way
for an up-scaling of the fermentation process. Therefore, biowaste was fermented
applying pH control, acid extraction and glucose addition in order to counteract
reasons such as acidification, end-product inhibition and carbon limitation,
respectively. The fermentation was competitive compared to other renewable lactic
acid production substrates and reached a maximum productivity of >5 g Clactic
acidg(-1)Ch(-1) and a concentration exceeding 30 g L(-1). A combination of
acidification and end-product inhibition was identified as major obstacle.
Lactobacillus crispatus and its closest relatives were identified as key lactic
acid producers within the process using Miseq Illumina sequencing.
PMID- 26433151
TI - Optimization of continuous lipid extraction from Chlorella vulgaris by CO2
expanded methanol for biodiesel production.
AB - CO2-expanded methanol (CXM) was used to extract lipids from the microalgae
Chlorella vulgaris (a total lipid content of 20.7% was determined by Soxhlet
extraction with methanol at 373 K for 96 h) in a continuous mode. The CXM was
found to be a superior solvent to methanol, ethanol, pressurized methanol and
ethanol, and CO2-expanded ethanol for lipid extraction. The effects of operation
variables including temperature, pressure and CO2 flow rate on extraction
performance were examined using the response surface and contour plot
methodologies. The optimal operating conditions were at a pressure of 5.5 MPa, a
temperature of 358 K, a methanol flow rate of 1 mL/min and a CO2 flow rate of 3.0
mL/min, providing an extracted lipid yield of 84.8 wt% over an extraction period
of 30 min. Compared with propane methanol mixture, CXM was safer and more energy
efficient for lipid extraction from C. vulgaris.
PMID- 26433152
TI - Sequential Heterotrophy-Dilution-Photoinduction Cultivation of Haematococcus
pluvialis for efficient production of astaxanthin.
AB - A novel cultivation strategy called "Sequential Heterotrophy-Dilution
Photoinduction" was successfully applied in the cultivation of Haematococcus
pluvialis to produce astaxanthin effectively. Cells were first cultivated
heterotrophically to achieve a high cell density, then were diluted to a suitable
concentration and switched to a favorable environment for cells acclimation.
Finally, the culture was transferred to high light environment for astaxanthin
accumulation. By this strategy, the dry cell weight of 26 g/L and biomass
productivity of 64.1mg/L/h were obtained in heterotrophy stage which surpassed
ever before reported in literatures. Meanwhile, the cells could accumulate
considerable astaxanthin up to 4.6% of dry cell weight after 10 days of
photoinduction. Furthermore, the application prospects of the strategy were
confirmed further by outdoor experiments. Therefore, this novel strategy provided
a promising approach for high-efficient production of natural astaxanthin from H.
pluvialis to meet the huge demand of this high value product.
PMID- 26433153
TI - Thermophilic bio-hydrogen production from corn-bran residue pretreated by
calcined-lime mud from papermaking process.
AB - This study investigated the use of calcined-lime mud from papermaking process
(CLMP) pretreatment to improve fermentative hydrogen yields from corn-bran
residue (CBR). CBR samples were pretreated with different concentrations (0-15
g/L) of CLMP at 55 degrees C for 48 h, prior to the thermophilic fermentation
with heat-treated anaerobic sludge inoculum. The maximum hydrogen yield (MHY) of
338.91 ml/g-VS was produced from the CBR pretreated with 10 g/L CLMP, with the
corresponding lag-phase time of 8.24h. Hydrogen yield increments increased from
27.76% to 48.07%, compared to the control. The CLMP hydrolyzed more cellulose,
which provided adequate substrates for hydrogen production.
PMID- 26433154
TI - Exploring the inhibitory characteristics of acid hydrolysates upon butanol
fermentation: A toxicological assessment.
AB - This study aimed to quantitatively evaluate the inhibitor tolerance of butanol
producing bacterium Clostridium acetobutylicum. The inhibitory effect of the
inhibitors generated by acid pretreatment of biomass feedstock on butanol
fermentation decreased in the order of formic acid>oxalic acid>furfural>5
HMF>Na2SO4. C. acetobutylicum has a small tolerance range for furfural (1.06
2.6g/L) and 5-HMF (1.99-2.3g/L). However, the inhibitory effect of Na2SO4 appears
to have a wide range, with a chronic toxicity for C. acetobutylicum. All the
results could explain, in quantitative manner, the instability of butanol
fermentation with C. acetobutylicum from various acid-pretreated feedstocks
caused by the fermentation inhibitors.
PMID- 26433155
TI - Growth of mono- and mixed cultures of Nannochloropsis salina and Phaeodactylum
tricornutum on struvite as a nutrient source.
AB - The suitability of crude and purified struvite (MgNH4PO4), a major precipitate in
wastewater streams, was investigated for renewable replacement of conventional
nitrogen and phosphate resources for cultivation of microalgae. Bovine effluent
wastewater stone, the source of crude struvite, was characterized for soluble
N/P, trace metals, and biochemical components and compared to the purified
mineral. Cultivation trials using struvite as a major nutrient source were
conducted using two microalgae production strains, Nannochloropsis salina and
Phaeodactylum tricornutum, in both lab and outdoor pilot-scale raceways in a
variety of seasonal conditions. Both crude and purified struvite-based media were
found to result in biomass productivities at least as high as established media
formulations (maximum outdoor co-culture yield ~20+/-4gAFDW/m(2)/day). Analysis
of nutrient uptake by the alga suggest that struvite provides increased nutrient
utilization efficiency, and that crude struvite satisfies the trace metals
requirement and results in increased pigment productivity for both microalgae
strains.
PMID- 26433156
TI - An integrated process for hydrogen-rich gas production from cotton stalks: The
simultaneous gasification of pyrolysis gases and char in an entrained flow bed
reactor.
AB - An integrated process (pyrolysis, gas-solid simultaneous gasification and
catalytic steam reforming) was utilized to produce hydrogen-rich gas from cotton
stalks. The simultaneous conversion of the pyrolysis products (char and pyrolysis
gases) was emphatically investigated using an entrained flow bed reactor. More
carbon of char is converted into hydrogen-rich gas in the simultaneous conversion
process and the carbon conversion is increased from 78.84% to 92.06% compared
with the two stages process (pyrolysis and catalytic steam reforming). The
distribution of tar components is also changed in this process. The polycyclic
aromatic compounds (PACs) of tar are converted into low-ring compounds or even
chain compounds due to the catalysis of char. In addition, the carbon deposition
yield over NiO/MgO catalyst in the steam reforming process is approximately 4
times higher without the simultaneous process. The potential H2 yield increases
from 47.71 to 78.19g/kg cotton stalks due to the simultaneous conversion process.
PMID- 26433157
TI - Phosphate adsorption ability of biochar/Mg-Al assembled nanocomposites prepared
by aluminum-electrode based electro-assisted modification method with MgCl2 as
electrolyte.
AB - In this work, the textural properties and phosphate adsorption capability of
modified-biochar containing Mg-Al assembled nanocomposites prepared by an
effective electro-assisted modification method with MgCl2 as an electrolyte have
been determined. Structure and chemical analyses of the modified-biochar showed
that nano-sized stonelike or flowerlike Mg-Al assembled composites, MgO, spinel
MgAl2O4, AlOOH, and Al2O3, were densely grown and uniformly dispersed on the
biochar surface. The adsorption isotherm and kinetics data suggested that the
biochar/Mg-Al assembled nanocomposites have an energetically heterogeneous
surface and that phosphate adsorption could be controlled by multiple processes.
The maximum phosphate adsorption capacity was as high as 887 mg g(-1), as fitted
by the Langmuir-Freundlich model, and is the highest value ever reported. It was
concluded that this novel electro-assisted modification is a very attractive
method and the biochar/Mg-Al assembled nanocomposites provide an excellent
adsorbent that can effectively remove phosphate from aqueous solutions.
PMID- 26433158
TI - Mining the coding and non-coding genome for cancer drivers.
AB - Progress in next-generation sequencing provides unprecedented opportunities to
fully characterize the spectrum of somatic mutations of cancer genomes. Given the
large number of somatic mutations identified by such technologies, the
prioritization of cancer-driving events is a consistent bottleneck. Most
bioinformatics tools concentrate on driver mutations in the coding fraction of
the genome, those causing changes in protein products. As more non-coding
pathogenic variants are identified and characterized, the development of
computational approaches to effectively prioritize cancer-driving variants within
the non-coding fraction of human genome is becoming critical. After a short
summary of methods for coding variant prioritization, we here review the highly
diverse non-coding elements that may act as cancer drivers and describe recent
methods that attempt to evaluate the deleteriousness of sequence variation in
these elements. With such tools, the prioritization and identification of cancer
implicated regulatory elements and non-coding RNAs is becoming a reality.
PMID- 26433159
TI - TLR7/8 agonists promote NK-DC cross-talk to enhance NK cell anti-tumor effects in
hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is a common cancer worldwide and the third leading
cause of cancer death. Immunotherapy is considered a promising treatment with the
aim to boost or arouse HCC-specific immune responses. TLR7 and TLR8 agonists are
effective immunomodulators and have been applied topically for the treatment of
certain skin tumors and viral infections. Here, we explored the role of TLR7 and
TLR8 agonists on the activation of dendritic cells (DCs) and natural killer (NK)
cells. We demonstrated that these agonists could directly activate NK cells,
promoting the maturation of immature DCs. Meanwhile, DCs also assisted in the
function of NK cells, resulting in enhanced anti-tumor immune responses to HCC.
Importantly, the combination therapy with NK cells stimulated with DCs and TLR7/8
agonist Gardiquimod (GDQ) significantly suppresses the growth of human HepG2
liver carcinoma xenografts. This study provides a new immunotherapeutic approach
for human HCC based on DC-NK cross-talk and also suggests that TLR7 and/or TLR8
agonists, particularly GDQ, may serve as potent innate and adaptive immune
response immunomodulators in tumor therapy.
PMID- 26433161
TI - Defects in 15-HETE Production and Control of Epithelial Permeability by Human
Enteric Glial Cells From Patients With Crohn's Disease.
AB - BACKGROUND & AIMS: Enteric glial cells (EGCs) produce soluble mediators that
regulate homeostasis and permeability of the intestinal epithelial barrier (IEB).
We investigated the profile of polyunsaturated fatty acid (PUFA) metabolites
produced by EGCs from rats and from patients with Crohn's disease (CD), compared
with controls, along with the ability of one of these metabolites, 15
hydroxyeicosatetraenoic acid (15-HETE), to regulate the permeability of the IEB.
METHODS: We isolated EGCs from male Sprague-Dawley rats, intestinal resections of
6 patients with CD, and uninflamed healthy areas of intestinal tissue from 6
patients who underwent surgery for colorectal cancer (controls). EGC-conditioned
media was analyzed by high-sensitivity liquid-chromatography tandem mass
spectrometry to determine PUFA signatures. We used immunostaining to identify 15
HETE-producing enzymes in EGCs and tissues. The effects of human EGCs and 15-HETE
on permeability and transepithelial electrical resistance of the IEB were
measured using Caco-2 cells; effects on signal transduction proteins were
measured with immunoblots. Levels of proteins were reduced in Caco-2 cells using
short-hairpin RNAs or proteins were inhibited pharmacologically. Rats were given
intraperitoneal injections of 15-HETE or an inhibitor of 15-lipoxygenase (the
enzyme that produces 15-HETE); colons were collected and permeability was
measured. RESULTS: EGCs expressed 15-lipoxygenase-2 and produced high levels of
15-HETE, which increased IEB resistance and reduced IEB permeability. 15-HETE
production was reduced in EGCs from patients with CD compared with controls. EGCs
from patients with CD were unable to reduce the permeability of the IEB; the
addition of 15-HETE restored permeability to levels of control tissues.
Inhibiting 15-HETE production in rats increased the permeability of the IEB in
colon tissues. We found that 15-HETE regulates IEB permeability by inhibiting an
adenosine monophosphate-activated protein kinase and increasing expression of
zonula occludens-1. CONCLUSIONS: Enteric glial cells from patients with CD have
reduced production of 15-HETE, which controls IEB permeability by inhibiting
adenosine monophosphate-activated protein kinase and increasing expression of
zonula occludens-1.
PMID- 26433160
TI - Activation of signal transduction pathways during hepatic oncogenesis.
AB - BACKGROUND AND AIMS: Understanding the molecular pathogenesis of hepatocellular
carcinoma (HCC) is essential to identify therapeutic targets. A hepatitis B virus
(HBV) related double transgenic murine model was developed. METHODS: Liver
specific expression of HBV X protein (HBx) and insulin receptor substrate 1
(IRS1) was achieved and transgenic mice were followed from birth to age 21
months. Liver and tumor tissue were assessed for histologic changes as well as
activation of signal transduction pathways by qRT-PCR and multiplex ELISA protein
assays. RESULTS: Overexpression of HBx and IRS1 stimulates liver cell
proliferation in the double transgenic mice. Only the male mice developed HCC
starting at age 15-18 months. The IN/IGF1/IRS1/MAPK/ERK and
IN/IGF1/IRS1/PI3K/AKT/GSK3beta cascades were activated early (6-9 months) in the
liver followed by WNT/beta-catenin and Notch signaling. Aspartate beta
hydroxylase (ASPH) was found to link these upstream growth factor signaling
pathways to downstream Notch activation in tumor tissues. CONCLUSIONS: Sustained
overexpression of HBx and IRS1 led to constitutive activation of a tripartite
growth factor signal transduction cascade in the liver and was necessary and
sufficient to promote HCC development and progression.
PMID- 26433162
TI - Could Carlos Chagas' assumption on the relationship between goiter and chronic
Chagas heart disease be correct? A historical reappraisal.
AB - In 1910, Chagas divided the clinical manifestations of the chronic form of Chagas
disease according to heart, Central Nervous System, and thyroid involvement,
particularly the presence of goiter. Chagas emphasized the association of goiter
with poor houses infested with kissing bugs, the similarity of the clinical
picture with that of patients underwent partial thyroidectomy, and with the
presence of thyroid sclerosis (inflammation) on histological examination. In
addition, Chagas observed that all people living in poor houses infested by
sucking bugs had goiter, contrasting with persons who lived in the same region,
drinking the same water, but living in good houses, which did not have goiter.
Furthermore, Chagas stressed the fact that people without any evidence of thyroid
disease that migrated to live in poor houses in areas infested by sucking bugs
developed thyroid disease some time later. Finally, and more importantly, Chagas
emphasized the association of goiter with cardiac abnormalities in 80% of
patients with chronic Chagas heart disease. Despite this, other authors working
in different regions did not confirm such an association. A reappraisal of data
from a work published in 1949 clearly shows that the presence of goiter was
statistically associated with chronic Chagas heart disease and with chronic
Chagas disease. Our paper highlights once more the grandiosity of Chagas' work,
which has been proved to be correct even in the history of goiter, and justifies
our claim for a posthumous Nobel Prize inasmuch as his work was not perceived by
the Karolinska Institute.
PMID- 26433163
TI - Comparison of transradial and transfemoral coronary intervention in octogenarians
with acute myocardial infarction.
AB - BACKGROUND: The transradial (TR) approach for percutaneous coronary intervention
(PCI) is challenging and associated with failure in elderly patients. We compared
the TR and transfemoral (TF) approaches in patients>80 years with acute
myocardial infarction (MI) undergoing PCI. METHODS: A total of 1945 (7.2%)
octogenarians were enrolled from among 27,129 patients in the Korea Acute
Myocardial Infarction Registry. The TR group (n=336, 17.3%) was compared with the
TF group (n=1609, 82.7%) in the overall and propensity-matched cohorts with
respect to procedural success, complications, in-hospital mortality, and one-year
mortality and total major adverse cardiac event (MACE; death, MI, and
revascularization) rate. RESULTS: In the overall cohort, the TR group had lower
incidence of Killip class III or IV compared to the TF group. The disease extent
and lesion severity were similar between groups, as was the procedural success
rate (97.7% vs. 98.3%); however, in-hospital complications were significantly
lower in the TR group (8.1% vs. 20.3%). In-hospital mortality was significantly
lower in the TR group than the TF group (3.4% vs. 11.4%), as were the one-year
mortality and total MACE (9.8% vs. 18.4% and 13% vs. 21.9%, respectively). These
outcomes were consistent in the propensity-matched cohort. The TR approach was
found to be a significant predictor of low in-hospital mortality (OR 0.355, 95%
CI 0.139-0.907), but not of one-year mortality (OR 0.644, 95% CI 0.334-1.240).
CONCLUSIONS: In octogenarians with acute MI undergoing PCI, the TR approach was
more effective than the TF approach as it had lower complication rate and better
clinical outcomes with comparable procedural success.
PMID- 26433164
TI - Targeted ablation of cardiac sympathetic neurons: A promising approach to prevent
sudden cardiac death.
PMID- 26433165
TI - Association between weekend admission for atrial fibrillation or flutter and in
hospital mortality, procedure utilization, length-of-stay and treatment costs.
PMID- 26433166
TI - The role of angioplasty in octogenarian patients with Acute Coronary Syndrome.
PMID- 26433167
TI - Worldwide disparities in cardiovascular disease: Challenges and solutions.
AB - The 20th century saw cardiovascular disease ascend as the leading cause of death
in the world. In response to the new challenge that heart disease imposed, the
cardiovascular community responded with ground breaking innovations in the form
of evidence based medications that have improved survival, imaging modalities
that allow for precise diagnosis and guide treatment; revascularization
strategies that have not only reduced morbidity, but also improved survival
following an acute myocardial infarction. However the benefits have not been
distributed equitably and as a result disparities have arisen in cardiovascular
care. There is tremendous data from the United States demonstrating the many
phenotypical forms of disparities. This paper takes a global view of disparities
and highlights that disparate care is not limited to the United States and it is
another challenge that the medical community should rise and face head on.
PMID- 26433168
TI - Identification of bioactive ingredients with immuno-enhancement and anti
oxidative effects from Fufang-Ejiao-Syrup by LC-MS(n) combined with bioassays.
AB - Fufang Ejiao Syrup (FES) is a widely used immune-boosting Traditional Chinese
Medicine (TCM) in Eastern Asian countries. This study attempts to investigate the
bioactive compounds in FES. First, FES extract was separated into fractions to
facilitate the investigation and 72 compounds were identified using LC-MS(n).
Subsequently, Immune-enhancement effects of FES and its components were
investigated on bone marrow cells and neuroprotective effects against H2O2
induced oxidative damage were evaluated in SH-SY5Y neuroblastoma cells and
bEnd.3. Our results indicated that fraction 3, 5, 6 and 8 showed significant
improvements on immune function, while several fractions had cytoprotective
effects against H2O2-induced oxidative injury. Jionoside A1 isolated from Radix
Rehmanniae Praeparata displayed dose dependent immune-enhancement activity. 20(R)
ginsenoside Rg3 could protect bEnd.3 against oxidative damage. Furthermore,
echinacoside, jionoside A1, vitexin-2-O-rhamnoside, acteoside and isoacteoside
possessed moderate protective activities on H2O2-treated SH-SY5Y cells. In
conclusion, our study provided both chemical and biological evidences to support
clinical application of FES.
PMID- 26433169
TI - Simultaneous determination of four furostanol glycosides in rat plasma by UPLC
MS/MS and its application to PK study after oral administration of Dioscorea
nipponica extracts.
AB - A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass
spectrometric (UPLC-MS/MS) method for simultaneous quantification of four
furostanol glycosides in rat plasma was established and validated. Ginsenoside
Rb1 was used as an internal standard. Plasma samples were pretreated by liquid
liquid extraction with n-butanol and chromatographed on a C18 column (2.1*50 mm
i.d., 2.6 MUm) using a gradient elution program consisting of acetonitrile and
water (containing 0.03% formic acid and 0.1 mM lithium acetate) at a flow rate of
0.4 mL/min. Lithium adduct ions were employed to enhance the response of the
analytes in electrospray positive ionization mode and multiple reaction
monitoring transitions were performed for detection. All calibration curves
exhibited good linearity (r>0.999) over the range of 10-20,000 ng/mL for
protodioscin and 2-4000 ng/mL for protogracillin, pseudoprotodioscin and
pseudoprotogracillin. The recoveries of the whole analytes were more than 80.3%
and exhibited no severe matrix effect. Meanwhile, the intra- and inter-day
precisions were all less than 10.7% and accuracies were within the range of -8.1
12.9%. The four saponins showed rapid excretion and relative high plasma
concentrations when the validated method was applied to the PK study of Dioscorea
nipponica extracts by intragastric administration at low, medium and high dose to
rats. Moreover, the T(1/2) and AUC(0-t) of each compound turned out to behave in
a dose-dependent pattern by comparing them at different dose levels.
PMID- 26433170
TI - Association of cervical precancer with human papillomavirus types other than 16
among HIV co-infected women.
AB - BACKGROUND: HIV-seropositive women face high risk for infection with oncogenic
human papillomavirus (oncHPV) types, abnormal Pap test results, and precancer,
but cervical cancer risk is only modestly increased. Human papillomavirus (HPV)16
is highly oncogenic but only weakly associated with HIV status and
immunosuppression, suggesting HPV16 may have a greater innate ability to evade
host immune surveillance than other oncHPV types, which in turn should result in
a greater relative increase in the prevalence of other oncHPV types among women
with cervical precancer. OBJECTIVE: We sought to assess whether the
underrepresentation of HPV16 among HIV-seropositive relative to HIV-seronegative
women remains among those with cervical precancers. STUDY DESIGN: HIV
seropositive and HIV-seronegative women in the Women's Interagency HIV Study were
screened for cervical intraepithelial neoplasia (CIN) grade >=3 (CIN3(+)). DNA
from >40 HPV types was detected by polymerase chain reaction in cervicovaginal
lavage specimens obtained at the visit at which CIN3(+) was diagnosed. RESULTS:
HPV16 was detected in 13 (62%) of 21 HIV-seronegative women with CIN3(+) but only
44 (29%) of 154 HIV-seropositive women with CIN3(+) (P = .01). The lower
prevalence of HPV16 in CIN3(+) among HIV-seropositive women persisted after
controlling for covariates (odds ratio [OR], 0.25; 95% confidence interval [CI],
0.08-0.78). The prevalence of other members of the HPV16-related alpha-9 oncHPV
clade as a group was similar in HIV-infected and uninfected women with CIN3(+)
(OR, 1.02; 95% CI, 0.53-1.94). The prevalence of non-alpha-9 oncHPV types was
increased in HIV-seropositive vs HIV-seronegative women with CIN3(+) (OR, 3.9;
95% CI, 1.3-11.8). CONCLUSION: The previously demonstrated increase in CIN3(+)
incidence among HIV-seropositive women is associated with lower HPV16 and higher
non-alpha-9 oncHPV prevalence. This is consistent with prior reports that HIV has
a weak effect on infection by HPV16 relative to other oncHPV and supports use of
nonavalent HPV vaccine in HIV-seropositive women.
PMID- 26433171
TI - Mortality rate of gestational trophoblastic neoplasia with a FIGO score of >=13.
AB - BACKGROUND: Gestational trophoblastic diseases include premalignant (partial and
complete hydatidiform moles) and malignant entities referred to as gestational
trophoblastic neoplasia. Use of the International Federation of Gynecology and
Obstetrics prognostic score is encouraged in cases of gestational trophoblastic
neoplasia to predict the potential for the development of resistance to single
agent chemotherapy. An International Federation of Gynecology and Obstetrics
score of >=7 defines a high-risk patient and requires combination chemotherapy.
Appropriate and rapid diagnosis, treatment by specialized centers, and reduction
of early deaths at the time of chemotherapy initiation have led to significant
improvements in survival for patients with high-risk gestational trophoblastic
neoplasia. There is a crucial need for the early identification of high-risk
patients with gestational trophoblastic neoplasia who have an increased death
risk to organize their treatment in highly specialized centers. OBJECTIVES: The
purpose of this study was to describe cases of gestational trophoblastic
neoplasia that have resulted in death, particularly in a subgroup with an
International Federation of Gynecology and Obstetrics prognostic score of >=13,
for whom low-dose etoposide and cisplatin induction chemotherapy recently was
shown to reduce early death rate. STUDY DESIGN: We identified 974 patients from
the French Center for Trophoblastic Diseases who had a diagnosis of gestational
trophoblastic neoplasia from November 1999 to March 2014. Among 140 patients who
were at high risk of resistance to single-agent chemotherapy (International
Federation of Gynecology and Obstetrics score, >=7), 29 patients (21%) had a
score of >=13. Mortality rate was estimated with the use of the Kaplan-Meier
method. RESULTS: The 5-year overall mortality rate, after the exclusion of
placental site trophoblastic tumors and epithelioid trophoblastic tumors, was 2%
for patients with gestational trophoblastic neoplasia (95% confidence interval,
1.25-3.13%). High-risk patients had a 5-year mortality rate of 12% (95%
confidence interval, 7.49-18.9%). Patients with an International Federation of
Gynecology and Obstetrics score of >=13 had a higher 5-year mortality rate
(38.4%; 95% confidence interval, 23.4-58.6%) and accounted for 52% of the deaths
in the entire cohort. Early deaths, defined as those that occur within 4 weeks
after treatment initiation, occurred in 8 patients of the entire cohort. Six of
them had an International Federation of Gynecology and Obstetrics score of >=13
at presentation, of whom 5 patients had brain and/or liver metastases.
CONCLUSION: Gestational trophoblastic diseases with an International Federation
of Gynecology and Obstetrics score of >=13 have an increased risk of early death.
We suggest that an International Federation of Gynecology and Obstetrics score of
>=13 becomes a consensual criterion for prediction of patients with gestational
trophoblastic neoplasia with increased risk of death, particularly early death.
These patients justify treatment in highly specialized gestational trophoblastic
disease centers and may benefit from the use of induction low-dose etoposide and
cisplatin.
PMID- 26433172
TI - Accelerated acidosis in response to variable fetal heart rate decelerations in
chronically hypoxic ovine fetuses.
AB - BACKGROUND: Due to limitations of technology, clinicians are typically unable to
determine if human fetuses are normoxic or moderately, chronically hypoxic. Risk
factors for chronic hypoxia include fetal growth restriction, which is associated
with an increased incidence of oligohydramnios and thus a risk for umbilical cord
occlusion (UCO) and variable fetal heart rate (FHR) decelerations. At delivery,
fetal growth restriction infants (<3rd percentile) have nearly twice the
incidence of low Apgar scores and umbilical pH <7.0. Despite the risks of
oligohydramnios and intermittent UCO, there is little understanding of the
acid/base responses rates of chronically hypoxic fetuses to variable FHR
decelerations as might occur during human labor. OBJECTIVE: We sought to compare
the increase in base deficit (BD) among chronically hypoxic as compared to
normoxic ovine fetuses in response to simulated mild, moderate, and severe
variable FHR decelerations. STUDY DESIGN: Near-term ovine fetuses were
chronically prepared with brachial artery catheters and an inflatable umbilical
cuff occluder. Following a recovery period, normoxic (n = 9) and spontaneously
hypoxic (n = 5) fetuses were identified (arterial O2 saturation <=55%). Both
animal groups underwent graded, 1-minute occlusions every 2.5 minutes with 1 hour
of mild (~30 beats/min [bpm] decrease from baseline), 1 hour of moderate (~60 bpm
decrease from baseline), and up to 2 hours of severe (~90 bpm decrease from
baseline) variable FHR decelerations until fetal arterial pH reached 7.00, when
occlusions were stopped. RESULTS: Repetitive UCO resulted in development of
acidosis (pH <7.0) in both groups. Hypoxic and normoxic fetuses demonstrated
similar BD increases in response to both mild (0.39, interquartile range [IQR]
0.28-0.45 vs 0.26, IQR 0.01-0.30 mEq/L/10 min, P = .25) and severe (1.97, IQR
1.50-2.43 vs 1.51, IQR 0.97-2.45 mEq/L/10 min, P = .63) variable decelerations.
However, moderate variable decelerations increased BD in hypoxic fetuses at 2.5
times the rate of normoxic fetuses (0.97, IQR 0.52-1.72 vs 0.39, IQR 0.23-0.47
mEq/L/10 min, P = .03). During the recovery period, hypoxic fetuses cleared BD
slower than normoxic fetuses (0.08 +/- 0.02 vs 0.12 +/- 0.03 mEq/L/min, P = .02).
CONCLUSION: In comparison to normoxic fetuses, hypoxic fetuses can more rapidly
progress to significant metabolic acidosis in response to moderate FHR variable
decelerations, and more slowly recover with in utero resuscitation, likely a
consequence of impaired placental function and fetal physiologic responses.
PMID- 26433173
TI - Comparative outcomes in older and younger women undergoing laparotomy or robotic
surgical staging for endometrial cancer.
AB - BACKGROUND: Older patients are at increased risk of perioperative morbidity and
mortality. There are limited data on the safety of a robotic approach in the
staging for endometrial cancer. OBJECTIVE: We compared outcomes in women
undergoing laparotomy or robotic surgical staging for endometrial cancer. STUDY
DESIGN: Using the Healthcare Cost and Utilization Project National Inpatient
Sample database from 2008 through 2010, we abstracted records for patients who
had surgery for endometrial cancer with either a robotic approach or laparotomy.
Patients were categorized by age (<65 vs >=65 years and 5-year increments).
Medical comorbidity scores were calculated using the Charlson Comorbidity Index.
Outcomes included intraoperative/perioperative/medical complications, death,
length of stay (LOS), and discharge disposition. Student t and chi(2) tests were
used to compare groups and approach. Multiple analysis of variance models were
used to compare differences between robotics and laparotomy and age groups.
RESULTS: We identified 16,980 patients who had surgery for endometrial cancer
with either a robotic approach (age >=65 years, n = 1228; age <65 years, n =
1574) or laparotomy (age >=65 years, n = 5914; age <65 years, n = 8264). Older
patients had a higher Charlson Comorbidity Index score at the time of surgery
(2.6 vs 2.5, P < .001). In laparotomy cases, intraoperative complication rates
were similar (4.1% vs 3.7%, P = .17). Older patients had higher rates of
perioperative surgical (20.5% vs 15.4%, P < .001) and medical (23.3% vs 15.5%, P
< .001) complications, longer LOS (5.1 vs 4.2 days, P < .001), and lower rates of
discharge to home (71.2% vs 90.1%, P < .001). In robotic cases, rates of
intraoperative complications were similar (5.9% vs 6.8%, P = .32). Older patients
had higher rates of perioperative surgical (8.3% vs 5.2%, P = .001) and medical
(12.3% vs 6.7%, P = .001) complications, longer LOS (2.00 vs 1.67 days, P <
.001), and lower rates of discharge to home (88.8% vs 96.8%, P < .001). With both
approaches, as age increased, perioperative surgical and medical complications
also increased in a linear fashion. In a subanalysis of older patients (n =
7142), there were lower rates of perioperative surgical (8.3% vs 20.5%, P < .001)
and medical (12.3% vs 23.3%, P < .001) complications, death (0.0% vs 0.8%, P <
.001), shorter LOS (2.00 vs 5.13 days, P < .001) and higher rate of discharge to
home (88.8% vs 71.2%, P < .001) in robotic compared to laparotomy cases.
CONCLUSION: Although the risks of surgery increase with age, in patients age >=65
years, a robotic approach for endometrial cancer appears to be safe given current
selection criteria utilized in the United States.
PMID- 26433174
TI - Single-step purification of chitosanases from Bacillus cereus using expanded bed
chromatography.
AB - A chitosanase-producing strain was isolated and identified as Bacillus cereus C
01. The purification and characterization of two chitosanases were studied. The
purification assay was accomplished by ion exchange expanded-bed chromatography.
Experiments were carried out in the presence and in the absence of cells through
different expansion degree to evaluate the process performance. The adsorption
experiments demonstrated that the biomass does not affect substantially the
adsorption capacity of the matrix. The enzyme bound to the resin with the same
extent using clarified and unclarified broth (0.32 and 0.30 U/g adsorbent,
respectively). The fraction recovered exhibited 31% of the yield with a 1.26-fold
increase on the specific activity concerned to the initial broth. Two
chitosanases from different elution steps were recovery. Chit A and Chit B were
stable at 30-60 degrees C, pH 5.5-8.0 and 5.5-7.5, respectively. The highest
activity was found at 55 degrees C, pH 5.5 to Chit A and 50 degrees C, pH 6.5 to
Chit B. The ions Cu(2+), Fe(2+) and Zn(2+) indicated inhibitory effect on
chitosanases activities that were significantly activated by Mn(2+). The
methodology applied in this study enables the partial purification of a stable
chitosanase using a feedstock without any pre-treatment using a single-step
purification.
PMID- 26433175
TI - Interaction of a snake venom L-amino acid oxidase with different cell types
membrane.
AB - Snake venom l-amino acid oxidases are multifunctional enzymes that exhibited a
wide range of pharmacological activities. Although it has been established that
these activities are primarily caused by the H2O2 generated in the enzymatic
reaction, the molecular mechanism, however, has not been fully investigated. In
this work, LAAO interaction with cytoplasmic membranes using different cell types
and Langmuir interfacial monolayers was evaluated. The Cerastes cerastes venom
LAAO (CC-LAAO) did not exhibit cytotoxic activities against erythrocytes and
peripheral blood mononuclear cells (PBMC). However, CC-LAAO caused cytotoxicity
on several cancer cell lines and induced platelet aggregation in dose-dependent
manner. Furthermore, the enzyme showed remarkable effect against Gram-positive
and Gram-negative bacteria. These activities were inhibited on the addition of
catalase or substrate analogs, suggesting that H2O2 liberation* is required for
these effects. Binding studies revealed that CC-LAAO binds to the cell surface
and enables the production of highly localized concentration of H2O2 in or near
the binding interfaces. On another hand, the interaction of CC-LAAO with a
mimetic phospholipid film was evaluated, for the first time, using a
monomolecular film technique. Results indicated that phospholipid/CC-LAAO
interactions are not involved in their binding to membrane and in their
pharmacological activities.
PMID- 26433176
TI - Yeast expressed ArtinM shares structure, carbohydrate recognition, and biological
effects with native ArtinM.
AB - Recent advances in glycobiology have revealed the essential role of lectins in
deciphering the glycocodes at the cell surface to generate important biological
signaling responses. ArtinM, a d-mannose-binding lectin isolated from the seeds
of jackfruit (Artocarpus heterophyllus), is composed of 16 kDa subunits that are
associated to form a homotetramer. Native ArtinM (n-ArtinM) exerts
immunomodulatory and regenerative effects, but the potential pharmaceutical
applicability of the lectin is highly limited by the fact that its production is
expensive, laborious, and impossible to be scaled up. This led us to characterize
a recombinant form of the lectin obtained by expression in Saccharomyces
cerevisiae (y-ArtinM). In the present study, we demonstrated that y-ArtinM is
similar to n-ArtinM in subunit arrangement, oligomerization and carbohydrate
binding specificity. We showed that y-ArtinM can exert n-ArtinM biological
activities such as erythrocyte agglutination, stimulation of neutrophil migration
and degranulation, mast cell degranulation, and induction of interleukin-12 and
interleukin-10 production by macrophages. In summary, the expression of ArtinM in
yeast resulted in successful production of an active, recombinant form of ArtinM
that is potentially useful for pharmaceutical application.
PMID- 26433177
TI - Facile synthesis of chitosan/ZnO bio-nanocomposite hydrogel beads as drug
delivery systems.
AB - ZnO nanoparticles were synthesized in situ during the formation of physically
cross-linked chitosan hydrogel beads using sodium tripolyphosphate as the cross
linker. The aim of the study was to investigate whether these nanocomposite beads
have the potential to be used in drug delivery applications. The formation of ZnO
nanoparticles (ZnONPs) in the hydrogels was confirmed by X-ray diffraction and
scanning electron microscopy studies. SEM micrographs revealed the formation of
ZnONPs with size range of 10-25 nm within the hydrogel matrix. Furthermore, the
swelling and drug release properties of the beads were studied. The prepared
nanocomposite hydrogels showed a pH sensitive swelling behavior. The ZnO
nanocomposite hydrogels have rather higher swelling ratio in different aqueous
solutions in comparison with neat hydrogel. In vitro drug release test was
carried out to prove the effectiveness of this novel type of nanocomposite beads
as a controlled drug delivery system. A prolonged and more controlled drug
releases were observed for ZnONPs containing chitosan beads, which increased by
the increase in ZnONPs content.
PMID- 26433179
TI - A comprehensive Y-STR portrait of Argentinean populations.
AB - A study of 23 Y-STRs was conducted in 257 individuals living in urban areas from
eight Argentinean provinces. The data were meta-analyzed together with 364
profiles obtained from the literature that represent other five provinces. A
total of 255 different haplotypes were observed (253 singletons). Genetic
structure estimated from analysis of molecular variance (AMOVA) and exploring
different grouping scenarios, yielded high within population variance. Not
surprisingly, analyses of genetic distances with respect to main ancestral
continental populations indicated Argentinean haplotypes to be closely related to
European ones. Overall, these results provide a quite complete picture of the
patterns of Y chromosome variation in Argentina, notably contributing to increase
the previous national database, and consequently allowing a better estimation of
parameters of interest in forensic casework and parentage testing.
PMID- 26433180
TI - Emerging issue of e-waste in Pakistan: A review of status, research needs and
data gaps.
AB - This review article focuses on the current situation of e-waste in Pakistan with
the emphasis on defining the major e-waste recycling sites, current and future
domestic generation of e-waste, hidden flows or import of e-waste and discusses
various challenges for e-waste management. Needed policy interventions and
possible measures to be taken at governmental level are discussed to avoid the
increasing problem of e-waste in the country. Our findings highlight that there
is still a general lack of reliable data, inventories and research studies
addressing e-waste related issues in the context of environmental and human
health in Pakistan. There is therefore a critical need to improve the current
knowledge base, which should build upon the research experience from other
countries which have experienced similar situations in the past. Further research
into these issues in Pakistan is considered vital to help inform future
policies/control strategies as already successfully implemented in other
countries.
PMID- 26433181
TI - The role of phytoplankton composition, biomass and cell volume in accumulation
and transfer of endocrine disrupting compounds in the Southern Baltic Sea (The
Gulf of Gdansk).
AB - Endocrine disrupting compounds (EDCs) like bisphenol A (BPA), 4-tert-octylphenol
(OP) and 4-nonylphenol (NP) are introduced to the trophic webs through among
others phytoplankton. This paper describes BPA, OP and NP concentrations in
phytoplankton in the Gulf of Gdansk (Southern Baltic Sea) in the years 2011-2012.
The assays of BPA, OP and NP in samples were performed using HPLC with
fluorescence detection. The concentrations of BPA, the most commonly used of the
three compounds, were over ten times higher than OP and NP concentrations. The
concentrations of the studied EDCs in phytoplankton from the Gulf of Gdansk
depended on anthropogenic factors and on phytoplankton properties (species
composition, biomass, volume). An increase in phytoplankton biomass did not
always result in an increase of BPA, OP and NP concentrations. However, the load
of the studied EDCs accumulated in phytoplankton biomass increase with a rise of
biomass. An increase in BPA, OP and NP concentrations was effected by biomass
growth and the proportions ofciliates, dinoflagellates, diatoms and green algae.
A strong positive correlation between OP and NP concentrations and negative
correlation between BPA concentrations and biomass of organisms with cells
measuring <1000 MUm(3) in volume results from the differing properties of these
compounds.
PMID- 26433182
TI - THE CHALLENGE OF CIEMAT INTERNAL DOSIMETRY SERVICE FOR ACCREDITATION ACCORDING TO
ISO/IEC 17025 STANDARD, FOR IN VIVO AND IN VITRO MONITORING AND DOSE ASSESSMENT
OF INTERNAL EXPOSURES.
AB - The accreditation of an Internal Dosimetry Service (IDS) according to ISO/IEC
17025 Standard is a challenge. The aim of this process is to guarantee the
technical competence for the monitoring of radionuclides incorporated in the body
and for the evaluation of the associated committed effective dose E(50). This
publication describes the main accreditation issues addressed by CIEMAT IDS
regarding all the procedures involving good practice in internal dosimetry,
focussing in the difficulties to ensure the traceability in the whole process,
the appropriate calculation of detection limit of measurement techniques, the
validation of methods (monitoring and dose assessments), the description of all
the uncertainty sources and the interpretation of monitoring data to evaluate the
intake and the committed effective dose.
PMID- 26433178
TI - Above the fray: Surface remodeling by secreted lysosomal enzymes leads to
endocytosis-mediated plasma membrane repair.
AB - The study of plasma membrane repair is coming of age. Mirroring human
adolescence, the field shows at the same time signs of maturity and significant
uncertainty, confusion and skepticism. Here we discuss concepts that emerged from
experimental data over the years, some of which are solidly established while
others are still subject to different interpretations. The firmly established
concepts include the critical requirement for Ca(2+) in wound repair, and the
role of rapid exocytosis of intracellular vesicles. Lysosomes are being
increasingly recognized as the major vesicles involved in injury-induced
exocytosis in many cell types, as a growing number of laboratories detect markers
for these organelles on the cell surface and lysosomal hydrolases in the
supernatant of wounded cells. The more recent observation of massive endocytosis
following Ca(2+)-triggered exocytosis initially came as a surprise, but this
finding is also being increasingly reported by different groups, shifting the
discussion to the mechanisms by which endocytosis promotes repair, and whether it
operates or not in parallel with the shedding of membrane blebs. We discuss how
the abundant intracellular vesicles that undergo homotypic fusion close to wound
sites, previously interpreted as exocytic membrane patches, actually acquire
extracellular tracers demonstrating their endocytic origin. We also suggest that
an initial, temporary patch that prevents cytosol loss until the bilayer is
restored might result not from vesicular fusion, but from rapid Ca(2+)-dependent
crosslinking and aggregation of cytosolic proteins. Finally, we propose that cell
surface remodeling, orchestrated by the extracellular release of lysosomal
hydrolases and perhaps also cytosolic molecules, may represent a key aspect of
the plasma membrane repair mechanism that has received little attention so far.
PMID- 26433183
TI - The effect of albendazole treatment on seizure outcomes in patients with
symptomatic neurocysticercosis.
AB - BACKGROUND: Randomized controlled trials have found an inconsistent effect of
anthelmintic treatment on long-term seizure outcomes in neurocysticercosis. The
objective of this study was to further explore the effect of albendazole
treatment on long-term seizure outcomes and to determine if there is evidence for
a differential effect by seizure type. METHODS: In this trial, 178 patients with
active or transitional neurocysticercosis cysts and new-onset symptoms were
randomized to 8 days of treatment with albendazole (n=88) or placebo (n=90), both
with prednisone, and followed for 24 months. We used negative binomial regression
and logistic regression models to determine the effect of albendazole on the
number of seizures and probability of recurrent or new-onset seizures,
respectively, over follow-up. RESULTS: Treatment with albendazole was associated
with a reduction in the number of seizures during 24 months of follow-up, but
this was only significant for generalized seizures during months 1-12 (unadjusted
rate ratio [RR] 0.19; 95% CI: 0.04-0.91) and months 1-24 (unadjusted RR 0.06; 95%
CI: 0.01-0.57). We did not detect a significant effect of albendazole on reducing
the number of focal seizures or on the probability of having a seizure,
regardless of seizure type or time period. CONCLUSIONS: Albendazole treatment may
be associated with some symptomatic improvement; however, this association seems
to be specific to generalized seizures. Future research is needed to identify
strategies to better reduce long-term seizure burden in patients with
neurocysticercosis.
PMID- 26433184
TI - Autism spectrum disorder symptoms in children with ADHD: A community-based study.
AB - This study examined the prevalence of autism spectrum disorder (ASD) symptoms in
a community-based sample of children with attention-deficit/hyperactivity
disorder (ADHD) and non-ADHD controls. We also examined the relationship between
ASD symptoms and ADHD subtype, ADHD symptom severity and child gender.
Participants were 6-10-year-old children (164 ADHD; 198 non-ADHD control)
attending 43 schools in Melbourne, Australia, who were participating in the
Children's Attention Project. ADHD was assessed in two stages using the parent
and teacher Conners' 3 ADHD index and the Diagnostic Interview Schedule for
Children IV (DISC-IV). ASD symptoms were identified using the Social
Communication Questionnaire (SCQ). Unadjusted and adjusted linear and logistic
regression examined continuous and categorical outcomes, respectively. Children
with ADHD had more ASD symptoms than non-ADHD controls (adjusted mean
difference=4.0, 95% confidence interval (CI) 2.8; 5.3, p<0.001, effect size=0.7).
Boys with ADHD had greater ASD symptom severity than girls with ADHD (adjusted
mean difference=2.9, 95% CI 0.8; 5.2, p=0.01, effect size=0.4). Greater ADHD
symptom severity was associated with greater ASD symptom severity (regression co
efficient=1.6, 95% CI 1.2; 2.0, p<0.001). No differences were observed by ADHD
subtype. Greater hyperactive/impulsive symptoms were associated with greater ASD
symptoms (regression coefficient=1.0; 95% CI 0.0; 2.0, p=0.04) however, this
finding attenuated in adjusted analyses (p=0.45). ASD symptoms are common in
children with ADHD. It is important for clinicians to assess for ASD symptoms to
ensure appropriate intervention.
PMID- 26433185
TI - History of preeclampsia is more predictive of cardiometabolic and cardiovascular
risk factors than obesity.
AB - OBJECTIVE: To determine to what extent a history of preeclampsia affects
traditional cardiometabolic (insulin resistance and dyslipidemia) and
cardiovascular (hypertension and micro-albuminuria) risk factors of the metabolic
syndrome irrespective of BMI. STUDY DESIGN: In a retrospective case-control study
we compared 90 formerly preeclamptic women, divided in 3 BMI-classes (BMI 19.5
24.9, 25.0-29.9, >=30.0kg/m(2)) to 30 controls, matched for BMI, age and parity.
Cardiometabolic and cardiovascular risk factors (WHO-criteria) were tested 6-18
months post partum. Statistical analysis included unpaired t-tests, Mann-Whitney
U test, or Chi square test and two-way ANOVA. RESULTS: Constituents of the
metabolic syndrome (glucose, insulin, HOMAIR, HDL-cholesterol, triglycerides,
blood pressure, micro-albuminuria) were higher in formerly preeclamptic women
than in BMI-matched controls. Resultantly, traditional risk factors were more
prevalent in formerly preeclamptic women than in controls (insulin resistance 80%
vs 30%, dyslipidemia 52% vs 3%, hypertension 24% vs 0%, micro-albuminuria 30% vs
0%). Cardiometabolic risk factors increased with BMI, to the same extent in both
groups. Formerly preeclamptic women had metabolic syndrome more often than their
BMI-matched controls (38% vs 3%, p<0.001). CONCLUSION: Traditional risk factors
of the metabolic syndrome are more prevalent in formerly preeclamptic women than
in BMI-matched controls and increase with BMI to the same extent in both groups.
A history of preeclampsia seems to be a stronger indicator of cardiovascular risk
than obesity per se.
PMID- 26433186
TI - Neurosteroids and potential therapeutics: Focus on pregnenolone.
AB - Considerable evidence from preclinical and clinical studies shows that steroids
and in particular neurosteroids are important endogenous modulators of several
brain-related functions. In this context, it remains to be elucidated whether
neurosteroids may serve as biomarkers in the diagnosis of disorders and might
have therapeutic potential for the treatment of these disorders. Pregnenolone
(PREG) is the main steroid synthesized from cholesterol in mammals and
invertebrates. PREG has three main sources of synthesis, the gonads, adrenal
glands and brain and is submitted to various metabolizing pathways which are
modulated depending on various factors including species, steroidogenic tissues
and steroidogenic enzymes. Looking at the whole picture of steroids, PREG is
often known as the precursor to other steroids and not as an active steroid per
se. Actually, physiological and brain functions have been studied mainly for
steroids that are very active either binding to specific intracellular receptors,
or modulating with high affinity the abundant membrane receptors, GABAA or NMDA
receptors. However, when high sensitive and specific methodological approaches
were available to analyze low concentrations of steroids and then match
endogenous levels of different steroid metabolomes, several studies have reported
more significant alterations in PREG than in other steroids in extraphysiological
or pathological conditions, suggesting that PREG could play a functional role as
well. Additionally, several molecular targets of PREG were revealed in the
mammalian brain and beneficial effects of PREG have been demonstrated in
preclinical and clinical studies. On this basis, this review will be divided into
three parts. The first provides a brief overview of the molecular targets of PREG
and the pharmacological effects observed in animal and human studies. The second
will focus on the possible functional role of PREG with an outline of the
modulation of PREG levels in animal and in human research. Finally, the review
will highlight the possible therapeutic uses of PREG that point towards the
development of pregnenolone-like molecules.
PMID- 26433187
TI - Enhanced Recovery After Surgery (ERAS) multimodal programme as experienced by
pancreatic surgery patients: Findings from an Italian qualitative study.
AB - BACKGROUND: ERAS has recently been implemented in pancreatic surgery settings,
but there is little evidence regarding the effects as perceived by patients.
Given the lack of the knowledge in the field, the aim of this study was to
capture the experience of patients undergoing pancreatic surgery who received
perioperative care based on the ERAS programme. METHODS: We designed a
qualitative study undertaken in the pancreatic surgery unit of San Raffaele
Hospital in Milan, Italy. Twenty-two consecutive patients were invited to
participate in the study and 13 patients were interviewed. Data was collected
between March and December 2012 either through face-to-face or semi-structured
telephone follow-up from three to six weeks after discharge. Data was analysed
using the interpretative phenomenological approach. RESULTS: Patients who
underwent surgical pancreatic procedures and treated with ERAS programme reported
experiences based on four themes: (1) Feeling prepared to face surgery, (2) Being
actively "inside" or "outside" the programme, (3) Healing at home: the best
setting, and (4) "Perceiving the ordinary as extraordinary": reaching
independence, once at home. CONCLUSION: According to the findings, uncomplicated
pancreatic surgery patients may benefit from the ERAS programme. Preadmission
counselling should help patients to assume an active role. Once the patient
returns home, the availability of a caregiver should be thoroughly assessed to
guarantee the support needed by patients to successfully complete the
ERAS(programme. Surgery and nursing staff should carefully monitor patients and
suggest whether they continue, interrupt, or individualise the scheduled ERAS
interventions in accordance with a patient's clinical condition and preferred
personal timing.
PMID- 26433188
TI - Inhibitory effects of arabitol on caries-associated microbiologic parameters of
oral Streptococci and Lactobacilli.
AB - The aim of this study was to compare arabitol with its better studied isomer
xylitol for their inhibitory effects on cell growth and acid production of oral
bacteria. Streptococcus mutans, Streptococcus salivarius and Streptococcus
sobrinus were used as representatives of oral streptococci and Lactobacillus
acidophilus and Lactobacillus fermentum were used for oral lactobacilli. Growth
was followed by measuring the absorbance at 660nm, acid production by pH change.
Sensitivity of these oral bacteria to arabitol and xylitol was first compared at
1% (65mM) additive concentration with glucose as sugar substrate. For all
bacteria tested, the inhibitory effects of the two polyols were comparable; both
were significantly stronger on streptococci (with 20-60% inhibition) than on
lactobacilli (with 5-10% inhibition). Effects of arabitol and xylitol were also
compared for S. mutans and S. salivarius in media with 1% of different sugar
substrates: glucose (55mM), fructose (55mM), galactose (55mM) and sucrose (30mM).
Inhibition occurred for all sugars: stronger on glucose and galactose (60-65%)
than on fructose and sucrose (40-45%). Inhibition dependency on the
arabitol/xylitol concentration from 0.01% (0.65mM) to 2% (130mM) was further
determined for S. mutans and S. salivarius. Regardless of the concentration,
sugar substrate and bacterial species tested, arabitol showed very similar
inhibition effects to its isomer xylitol.
PMID- 26433189
TI - The effects of dental pulp stem cells on bone regeneration in rat calvarial
defect model: micro-computed tomography and histomorphometric analysis.
AB - OBJECTIVE: Stem cell therapies may be applicable to all fields of medicine,
including craniomaxillofacial surgery. Dental pulp stem cells also have
significant osteogenic properties. This study aimed to evaluate the influence of
dental pulp stem cells on bone regeneration and to ascertain whether or not there
was any superiority over traditional methods. DESIGN: In this study, 15 non
immunodeficient Wistar albino rats were used. The rats were divided into three
groups: (1) untreated control group; (2) hydroxyapatite tri-calcium-phosphate
(HA/TCP) paste; (3) human dental pulp derived stem cells (DPSC) mixed with HA/TCP
paste (HA/TCP+DSPC group, n=10). Two symmetrical full-thickness cranial defects
were created on each parietal region (10 defects for each group). The animals
were sacrificed 8 weeks post-surgery and samples were analyzed by microcomputer
tomography (MU-CT) and histomorphometry. RESULTS: The calcification rate and bone
mineral density (BMD) values in Group 3 were found to be significantly higher
than in the other two groups. Radiographically, bone regeneration was greater in
Group 2 compared with the control group. However, there was no significant
difference between Groups 2 and 1 in respect of histological analysis.
CONCLUSIONS: According to the results of the present study, DPSCs may be a
suitable factor for bone tissue engineering because they can be easily obtained
and differentiate into bone cells.
PMID- 26433190
TI - Histologic features and fascicular arrangement of the inferior alveolar nerve.
AB - OBJECTIVES: Knowledge of the various possible morphologies and courses of the
inferior alveolar nerve and artery is important for successful and safe surgical
procedures in the mandibular region. The purpose of this study was to verify the
histologic features and fascicular arrangement of the inferior alveolar nerve and
artery relative to tooth region. MATERIALS AND METHODS: Twenty embalmed dentulous
hemimandibles were examined (eight males and two females; mean age, 58.2 years).
The hemimandibles were prepared for routine histology and stained with
hematoxylin-eosin and Masson's trichrome. The histologic features, fascicular
arrangement, courses, and areas of the inferior alveolar nerve and artery were
investigated with the aid of a light microscope. RESULTS: The inferior alveolar
neurovascular bundle comprised the inferior alveolar nerve, which appeared as a
large trunk comprising two major nerves (the mental and dental nerves), and the
inferior alveolar artery, which occupied a relatively small portion of the
bundle. The mental nerve was located inferolingually in the third molar region
and turned to the buccal side in the first molar region, separating from the
dental nerve before reaching the mental foramen. The mandibular incisive canal
with a bony wall was not found in the lateral incisor region; instead, small
dental nerve fascicles and arteries presented consistently in the intertrabecular
spaces. The inferior alveolar artery traveled above the inferior alveolar nerve
over the entire mandibular canal. CONCLUSIONS: These results provide data that
are relevant to treatment planning for operative procedures such as implant
placement, endodontic treatment, and osteotomy in the mandibular region.
PMID- 26433192
TI - Head and neck cancer among marijuana users: a meta-analysis of matched case
control studies.
AB - OBJECTIVES: The scientific literature presents conflicting data on a possible
causal relationship between marijuana users and the development of head and neck
cancer. DESIGN: This study performed a systematic review with meta-analysis.
Articles were selected from various electronic databases using keywords obtained
from the Medical Subject Headings (MeSH). After reading by three reviewers and
scoring of methodological quality, six articles (totaling nine case-control
studies) were assessed with Comprehensive Meta-Analysis((r)) software. The value
of effect (odds ratio) was calculated, which represented the chance of developing
head and neck cancer between individuals who had smoked marijuana in their
lifetime in models controlled for age, gender, race, and tobacco consumption.
RESULTS: Approximately 12.6% of cases and 14.3% of controls were marijuana users.
The meta-analysis found no association between exposure and disease (OR=1.021; IC
95%=0.912-1.14; p=0.718). CONCLUSION: No association between lifetime marijuana
use and the development of head and neck cancer was found. The different methods
of collection/presentation of results in the selected articles prevented other
analyzes from being conducted. Additional studies are needed to assess for long
term effects.
PMID- 26433191
TI - FGF2 gene activated matrices promote proliferation of bone marrow stromal cells.
AB - BACKGROUND: In this study, we report on the results from the development and
early in vitro testing of a gene activated matrix encoding basic human fibroblast
growth factor 2 (FGF2) in bone marrow stromal cells (BMSCs). METHODS:
Polyethylenimine (PEI), a cationic polymer, was utilized as a gene delivery
vector and collagen scaffolds were used as the carrier to deliver the PEI-pDNA
nano-sized complexes (nanoplexes) encoding the FGF2 protein. Initially, the BMSCs
were transfected in vitro with the PEI-pFGF2 nanoplexes, prepared at a N/P ratio
of 10, with cells alone and naked DNA as controls. This was followed by
transfection experiments using collagen scaffold containing complexes, with the
scaffold alone as a control. The transfection efficacy of the nanoplexes was
assessed using ELISA for the determination of FGF2 protein expressed by the
transfected cells. The functionality of transfection was assessed by evaluating
cellular recruitment, attachment, and proliferation of BMSCs on the scaffold
using imaging techniques. RESULTS: BMSCs transfected with the PEI-pFGF2
nanoplexes (either alone or within the scaffold) led to higher expression of
FGF2, compared to controls. Scanning electron microscopy and confocal imaging
confirmed the recruitment and attachment of BMSCs to scaffolds containing the PEI
pFGF2 nanoplexes. Confocal microscopy showed a significantly higher number of
proliferating cells within PEI-pFGF2 nanoplex-loaded scaffolds than with empty
scaffolds. CONCLUSIONS: This first in vitro evaluation in BMSCs provides evidence
that gene activated matrices (GAMs) encoding the FGF2 protein may have strong
translational potential for clinical applications that require enhanced osseous
and periodontal tissue regeneration.
PMID- 26433193
TI - Objective assessment of actual chewing side by measurement of bilateral masseter
muscle electromyography.
AB - OBJECTIVE: The aim of this study was to examine the validity of objective
assessment of actual chewing side by measurement of electromyographic (EMG)
activity of the bilateral masseter muscles upon chewing test foods. DESIGN: The
sample consisted of 19 healthy, dentate individuals. The subjects were asked to
chew three types of test foods (peanuts, beef jerky, and chewing gum) for 10
strokes on the right side and then on the left side, and instructed to perform
maximum voluntary clenching for 3s, three times. EMG activity from the bilateral
masseter muscles was recorded. The data were collected in three different days.
The root mean square EMG amplitude obtained from the maximum clenching task was
used as the maximum voluntary contraction (MVC). Then, the level of amplitude
against the MVC (%MVC) was calculated for the right and left sides on each
stroke. The side with the larger %MVC value was judged as the chewing side, and
the concordance rates (CRs) for the instructed chewing side (ICS) and the judged
chewing side (JCS) were calculated. Intraclass correlation coefficients (ICCs) of
the CRs were calculated to evaluate the reproducibility of the method. RESULTS:
High CRs between the ICS and JCS for each test food were recognized. There were
significant ICCs for beef jerky (R=0.761, P<0.001) and chewing gum (R=0.785,
P<0.001). CONCLUSIONS: The results suggested that the measurement of EMG activity
from the bilateral masseter muscles may be a useful method for the objective
determination of the actual chewing side during mastication.
PMID- 26433194
TI - Coordination of AUF1 and miR-148a destabilizes DNA methyltransferase 1 mRNA under
hypoxia in endometriosis.
AB - STUDY HYPOTHESIS: DNA methylation is regulated by hypoxia in endometriosis. STUDY
FINDING: Hypoxia causes global hypomethylation through AU-rich element binding
factor 1 (AUF1)/microRNA-148a (miR-148a)-mediated destabilization of DNA
methyltransferase 1 (DNMT1) mRNA. WHAT IS KNOWN ALREADY: Eutopic endometrial and
ectopic endometriotic stromal cells have the same genetic background, but differ
in several cellular and molecular responses. Both hypoxia and DNA methylation
regulate several genes involved in the development of endometriosis. STUDY
DESIGN, SAMPLES/MATERIALS, METHODS: This laboratory study included 15 patients of
reproductive age with endometriosis or normal menstrual cycles. Paired
endometrial and endometriotic tissues were collected for assaying the levels of
DNMT1, 3a and 3b using quantitative RT-PCR, western blot and immunohistochemical
(IHC) staining. Primary cultured endometrial stromal cells maintained in
normoxia/hypoxia (1% O2) or treated with hypoxia-mimetic compounds were also
assayed. The levels of DNA 5-methylcytosine were assayed by using IHC in clinical
specimens and murine tissues, and by ELISA in cultured stromal cells. The 3'
untranslated region reporter assay was used to evaluate the effect of hypoxia,
microRNAs (miRNAs) and human antigen R (HuR)/AUF1 on DNMT1 mRNA stability. RNA
immunoprecipitation was used to assess the interaction of HuR/AUF1 and miR
148a/DNMT1 mRNA under hypoxia. Finally, a transplant-induced mouse model of
endometriosis using 20 mice was used to elucidate the alteration of Dnmt1 levels
and DNA methylation in the endometriotic tissues. MAIN RESULTS AND THE ROLE OF
CHANCE: Levels of DNMT1 mRNA and protein and 5-methylcytosine were lower in the
ectopic stromal cells (P < 0.05) than in the eutopic cells. Treatment with
hypoxia and its mimetic compounds recapitulated the reduced levels of DNMT1 and 5
methylcytosine levels (P < 0.05 versus control). Hypoxia treatment destabilized
DNMT1 mRNA through recruitment of miR-148a and AUF1. Mutations introduced to the
miR-148a targeting site or AU-rich element (ARE) restored the hypoxia-suppressed
DNMT1 3'-untranslated region (3'-UTR) reporter activity (P < 0.05 versus
control). Levels of proteins of three hypermethylated genes in endometrial stroma
cells, GATA6, HOXA3 and SLC16A5, were elevated after 72 h of hypoxia treatment (P
< 0.05 versus control). Finally, a transplant-induced model of endometriosis
demonstrated the down-regulation of DNMT1 and a decrease in 5-methylcytosine in
the endometriotic tissues (P < 0.05, eutopic versus ectopic). LIMITATIONS,
REASONS FOR CAUTION: Primary human cell cultures and a murine model were used in
this study, and thus the results may not fully represent the situation in vivo.
WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to elucidate how
microenvironmental hypoxia links to the epigenetic effects of DNA methylation in
the endometriosis, and to delineate the molecular mechanism of hypoxia
coordinated AUF1/miR-148a interaction and recruitment to DNMT1 mRNA during the
pathogenesis of endometriosis. The development of future therapeutics in
endometriosis may aim at disrupting this specific interaction and eventually
restore the epigenetic regulation. STUDY FUNDING AND COMPETING INTERESTS: This
work was supported by the National Science Council of Taiwan (NSC101-2320-B-006
030-MY3). The author declares that there are no conflicts of interest.
PMID- 26433195
TI - Children With Mild Bilateral and Unilateral Hearing Loss: Parents' Reflections on
Experiences and Outcomes.
AB - Children with mild bilateral and unilateral hearing loss are now commonly
identified early through newborn hearing screening initiatives. There remains
considerable uncertainty about how to support parents and about which services to
provide for children with mild bilateral and unilateral hearing loss. The goal of
this study was to learn about parents' experiences and understand, from their
perspectives, the impact of hearing loss in the mild range on the child's
functioning. Parents of 20 children in Ontario, Canada, participated in the
study. The median age of identification of hearing loss was 4.6 months
(interquartile range: 3.6, 10.8). Parents appreciated learning early about
hearing loss, but their experiences with the early process were mixed. Parents
felt that professionals minimized the importance of milder hearing loss. There
was substantial uncertainty about the need for hearing aids and the findings
suggest that parents need specific guidance. Parents expressed concerns about the
potential impact of hearing loss on their child's development, particularly at
later ages.
PMID- 26433196
TI - Expertise in unexpected places: Children's acceptance of information from gender
counter-stereotypical experts.
AB - The current study examined children's willingness to accept novel information
from expert informants with nontraditional gender role interests. Four- to 8-year
olds heard conflicting information about traditionally feminine or masculine
domains from a gender counter-stereotypical expert (e.g., a boy with expertise in
ballet) and a layperson of the other gender (e.g., a girl with little knowledge
about ballet). Participants were asked which informant was correct, who they
would prefer to learn from in the future, and to rate their liking of each
informant. Overall, participants selected the gender counter-stereotypical expert
as correct. Four- to 5-year-olds reported a preference to learn from same-gender
participants in the future irrespective of expertise, whereas 6- to 8-year-olds
reported wanting to learn from counter-stereotypical experts. Boys showed
relatively greater acceptance of information from a male counter-stereotypical
expert than from a female counter-stereotypical expert. Although participants
reported greater liking of same-gender informants, liking evaluations were
largely positive irrespective of gender norm deviations. Implications for
children's acceptance of gender nonconforming activities are discussed.
PMID- 26433197
TI - Thalamic segmentation based on improved fuzzy connectedness in structural MRI.
AB - Thalamic segmentation serves an important function in localizing targets for deep
brain stimulation (DBS). However, thalamic nuclei are still difficult to identify
clearly from structural MRI. In this study, an improved algorithm based on the
fuzzy connectedness framework was developed. Three-dimensional T1-weighted images
in axial orientation were acquired through a 3D SPGR sequence by using a 1.5 T GE
magnetic resonance scanner. Twenty-five normal images were analyzed using the
proposed method, which involved adaptive fuzzy connectedness combined with
confidence connectedness (AFCCC). After non-brain tissue removal and contrast
enhancement, the seed point was selected manually, and confidence connectedness
was used to perform an ROI update automatically. Both image intensity and local
gradient were taken as image features in calculating the fuzzy affinity.
Moreover, the weight of the features could be automatically adjusted. Thalamus,
ventrointermedius (Vim), and subthalamic nucleus were successfully segmented. The
results were evaluated with rules, such as similarity degree (SD), union overlap,
and false positive. SD of thalamus segmentation reached values higher than 85%.
The segmentation results were also compared with those achieved by the region
growing and level set methods, respectively. Higher SD of the proposed method,
especially in Vim, was achieved. The time cost using AFCCC was low, although it
could achieve high accuracy. The proposed method is superior to the traditional
fuzzy connectedness framework and involves reduced manual intervention in time
saving.
PMID- 26433198
TI - Retrovirus-based vectors for transient and permanent cell modification.
AB - Retroviral vectors are commonly employed for long-term transgene expression via
integrating vector technology. However, three alternative retrovirus-based
platforms are currently available that allow transient cell modification. Gene
expression can be mediated from either episomal DNA or RNA templates, or selected
proteins can be directly transferred through retroviral nanoparticles. The
different technologies are functionally graded with respect to safety, expression
magnitude and expression duration. Improvement of the initial technologies,
including modification of vector designs, targeted increase in expression
strength and duration as well as improved safety characteristics, has allowed
maturation of retroviral systems into efficient and promising tools that meet the
technological demands of a wide variety of potential application areas.
PMID- 26433200
TI - Within- and trans-generational effects of herbivores and detritivores on plant
performance and reproduction.
AB - Mutualistic and antagonistic above-ground and below-ground species have the
potential to be involved in strong interactions that can either weaken or
strengthen their individual impacts on plants. Their impacts can also have
delayed effects on a plant's progeny by altering offspring traits and survival.
Few studies have explored the effect of herbivore and detritivore interactions
with parent plants on offspring vital life-cycle processes, such as seedling
emergence rate, seedling establishment and offspring survival. In the field, I
experimentally studied the combined effects of floral herbivores (FH), root
herbivores (RH) and detritivores on plant growth and reproduction of Moricandia
moricandioides (Brassicaceae). In particular, I analysed the trans-generational
effects of herbivores and detritivores on seed and juvenile production as well as
on vital life-cycle processes (i.e. seedling emergence rates, survival). Floral
herbivores strongly reduced the number of flowers, fruits, seeds and juveniles.
Detritivores had an impact on plant success by increasing seed quality (% N and N
: C ratio), although the effect was altered by the presence of floral and RH. I
found maternal effects (trans-generational effects) of FH, RH and detritivores.
Floral herbivores reduced seedling emergence and establishment. Floral and RH in
combination reduced seedling emergence timing, but the effect was counteracted by
detritivores. Detritivores also reduced the negative effect of FH on offspring
mortality rate. This study shows that the impact of above-ground and below-ground
organisms on M. moricandioides plants go beyond seed production and were evident
in the probability of establishment and survival of the following generation.
Trans-generational effects were induced by all three groups of interacting
organisms and the net consequences for plant offspring depended on the organisms
interacting with the plant.
PMID- 26433199
TI - Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to
microglia/macrophages in the brain.
AB - BACKGROUND: To understand the ability of gliomas to manipulate their
microenvironment, we visualized the transfer of vesicles and the effects of tumor
released extracellular RNA on the phenotype of microglia in culture and in vivo.
METHODS: Extracellular vesicles (EVs) released from primary human glioblastoma
(GBM) cells were isolated and microRNAs (miRNAs) were analyzed. Primary mouse
microglia were exposed to GBM-EVs, and their uptake and effect on proliferation
and levels of specific miRNAs, mRNAs, and proteins were analyzed. For in vivo
analysis, mouse glioma cells were implanted in the brains of mice, and EV release
and uptake by microglia and monocytes/macrophages were monitored by intravital 2
photon microscopy, immunohistochemistry, and fluorescence activated cell sorting
analysis, as well as RNA and protein levels. RESULTS: Microglia avidly took up
GBM-EVs, leading to increased proliferation and shifting of their cytokine
profile toward immune suppression. High levels of miR-451/miR-21 in GBM-EVs were
transferred to microglia with a decrease in the miR-451/miR-21 target c-Myc mRNA.
In in vivo analysis, we directly visualized release of EVs from glioma cells and
their uptake by microglia and monocytes/macrophages in brain. Dissociated
microglia and monocytes/macrophages from tumor-bearing brains revealed increased
levels of miR-21 and reduced levels of c-Myc mRNA. CONCLUSIONS: Intravital
microscopy confirms the release of EVs from gliomas and their uptake into
microglia and monocytes/macrophages within the brain. Our studies also support
functional effects of GBM-released EVs following uptake into microglia,
associated in part with increased miRNA levels, decreased target mRNAs, and
encoded proteins, presumably as a means for the tumor to manipulate its environs.
PMID- 26433201
TI - Transcription factors WRKY70 and WRKY11 served as regulators in rhizobacterium
Bacillus cereus AR156-induced systemic resistance to Pseudomonas syringae pv.
tomato DC3000 in Arabidopsis.
AB - The activation of both the SA and JA/ETsignalling pathways may lead to more
efficient general and broad resistance to Pst DC3000 by non-pathogenic
rhizobacteria. However, the mechanisms that govern this simultaneous activation
are unclear. Using Arabidopsis as a model system, two transcription factors,
WRKY11 and WRKY70, were identified as important regulators involved in Induced
Systemic Resistance (ISR) triggered by Bacillus cereus AR156. The results
revealed that AR156 treatment significantly stimulated the transcription of
WRKY70, but suppressed that of WRKY11 in Arabidopsis leaves. Furthermore, they
were shown to be required for AR156 enhancing the activation of cellular defence
responses and the transcription level of the plant defence response gene.
Overexpression of the two transcription factors in Arabidopsis also showed that
they were essential for AR156 to elicit ISR. AR156-triggered ISR was completely
abolished in the double mutant of the two transcription factors, but still
partially retained in the single mutants, indicating that the regulation of the
two transcription factors depend on two different pathways. The target genes of
the two transcription factors and epistasis analysis suggested that WRKY11
regulated AR156-triggered ISR through activating the JA signalling pathway, and
WRKY70 regulated the ISR through activating the SA signalling pathway. In
addition, both WRKY11 and WRKY70 modulated AR156-triggered ISR in a NPR1
dependent manner. In conclusion, WRKY11 and WRKY70 played an important role in
regulating the signalling transduction pathways involved in AR156-triggered ISR.
This study is the first to illustrate the mechanism by which a single
rhizobacterium elicits ISR by simultaneously activating both the SA and JA/ET
signalling pathways.
PMID- 26433203
TI - Streptococcal toxins: role in pathogenesis and disease.
AB - Group A Streptococcus (Streptococcus pyogenes), group B Streptococcus
(Streptococcus agalactiae) and Streptococcus pneumoniae (pneumococcus) are host
adapted bacterial pathogens among the leading infectious causes of human
morbidity and mortality. These microbes and related members of the genus
Streptococcus produce an array of toxins that act against human cells or tissues,
resulting in impaired immune responses and subversion of host physiological
processes to benefit the invading microorganism. This toxin repertoire includes
haemolysins, proteases, superantigens and other agents that ultimately enhance
colonization and survival within the host and promote dissemination of the
pathogen.
PMID- 26433202
TI - Mutation in Brachypodium caffeic acid O-methyltransferase 6 alters stem and grain
lignins and improves straw saccharification without deteriorating grain quality.
AB - Cereal crop by-products are a promising source of renewable raw material for the
production of biofuel from lignocellulose. However, their enzymatic conversion to
fermentable sugars is detrimentally affected by lignins. Here the
characterization of the Brachypodium Bd5139 mutant provided with a single
nucleotide mutation in the caffeic acid O-methyltransferase BdCOMT6 gene is
reported. This BdCOMT6-deficient mutant displayed a moderately altered
lignification in mature stems. The lignin-related BdCOMT6 gene was also found to
be expressed in grains, and the alterations of Bd5139 grain lignins were found to
mirror nicely those evidenced in stem lignins. The Bd5139 grains displayed
similar size and composition to the control. Complementation experiments carried
out by introducing the mutated gene into the AtCOMT1-deficient Arabidopsis mutant
demonstrated that the mutated BdCOMT6 protein was still functional. Such a
moderate down-regulation of lignin-related COMT enzyme reduced the straw
recalcitrance to saccharification, without compromising the vegetative or
reproductive development of the plant.
PMID- 26433204
TI - Characterization of antioxidant phenolics in Syringa vulgaris L. flowers and
fruits by HPLC-DAD-ESI-MS.
AB - In this study the polyphenolic composition of lilac flowers and fruits was
determined for the first time. For the identification of compounds, accurate
molecular masses and formulas, acquired by LC and ESI-TOF-MS and fragmentation
pattern given by LC-ESI/MS/MS analyses, were used. Our chromatographic system in
conjunction with tandem MS was found to be valuable in the rapid separation and
determination of the multiple constituents in methanolic extracts of lilac
flowers and fruits. Altogether 34 phenolics, comprising 18 secoiridoids, seven
phenylpropanoids, four flavonoids and five low-molecular-weight phenols, were
identified. As marker compounds two secoiridoids (oleuropein and nuzhenide), two
phenylpropanoids (acteoside and echinacoside) and rutin were quantified by
validated methods. As a result of quantitative analysis, it was confirmed that
flowers contain significant amounts of phenylpropanoids (acteoside, 2.48%;
echinacoside, 0.75%) and oleuropein (0.95%), while in fruits secoiridoid
oleuropein (1.09%) and nuzhenide (0.42%) are the major secondary metabolites. The
radical scavenging activities of the extracts and the constituents were
investigated by DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS [2,2'-azino-bis-(3
ethylbenzothiazoline-6-sulfonic acid)] assays. Both extracts show remarkable
antioxidant activities. Our results clearly show that lilac flowers and fruits
are inexpensive, readily available natural sources of phenolic compounds with
pharmacological and cosmetic applications. Copyright (c) 2015 John Wiley & Sons,
Ltd.
PMID- 26433205
TI - lincRNA-p21 inhibits hepatic stellate cell activation and liver fibrogenesis via
p21.
AB - Long non-coding RNAs are involved in various biological processes and diseases.
The biological role of long intergenic non-coding RNA-p21 (lincRNA-p21) in liver
fibrosis remains unknown before this study. In this study, we observed marked
reduction of lincRNA-p21 expression in mice liver fibrosis models and human
cirrhotic liver. Over-expression of lincRNA-p21 suppressed activation of hepatic
stellate cells (HSCs) in vitro. Lentivirus-mediated lincRNA-p21 transfer into
mice decreased the severity of liver fibrosis in vivo. Additionally, lincRNA-p21
reversed the activation of HSCs to their quiescent phenotype. The mRNA levels of
lincRNA-p21 and p21 were positively correlated. Our results show that over
expression of lincRNA-p21 promotes up-regulation of p21 at both the mRNA and
protein levels. Furthermore, lincRNA-p21 inhibited cell-cycle progression and
proliferation of primary HSCs through enhancement of p21 expression. Compared
with healthy subjects, serum lincRNA-p21 levels were significantly lower in
patients with liver cirrhosis, especially those with decompensation. These
findings collectively indicate that lincRNA-p21 is a mediator of HSC activation,
supporting its utility as a novel therapeutic target for liver fibrosis.
PMID- 26433206
TI - Long-Term Follow-Up of the Edmonton Protocol of Islet Transplantation in the
United States.
AB - We report the long-term follow-up of the efficacy and safety of islet
transplantation in seven type 1 diabetic subjects from the United States enrolled
in the multicenter international Edmonton Protocol who had persistent islet
function after completion of the Edmonton Protocol. Subjects were followed up to
12 years with serial testing for sustained islet allograft function as measured
by C-peptide. All seven subjects demonstrated continued islet function longer
than a decade from the time of first islet transplantation. One subject remained
insulin independent without the need for diabetic medications or supplemental
transplants. One subject who was insulin-independent for over 8 years experienced
graft failure 10.9 years after the first islet transplant. The remaining six
subjects demonstrated continued islet function upon trial completion, although
three had received a supplemental islet transplant each. At trial completion,
five subjects were receiving insulin and two remained insulin independent,
although one was treated with liraglutide. The median hemoglobin A1c was 6.3% (45
mmol/mol). All subjects experienced progressive decline in the C-peptide/glucose
ratio. No patients experienced severe hypoglycemia, opportunistic infection, or
lymphoma. Thus, although the rate and duration of insulin independence was low,
the Edmonton Protocol was safe in the long term. Alternative approaches to islet
transplantation are under investigation.
PMID- 26433207
TI - Low alanine aminotransferase levels and higher number of cardiovascular events in
people with Type 2 diabetes: analysis of the Fenofibrate Intervention and Event
Lowering in Diabetes (FIELD) study.
AB - AIMS: To determine whether alanine aminotransferase or gamma-glutamyltransferase
levels, as markers of liver health and non-alcoholic fatty liver disease, might
predict cardiovascular events in people with Type 2 diabetes. METHODS: Data from
the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed
to examine the relationship between liver enzymes and incident cardiovascular
events (non-fatal myocardial infarction, stroke, coronary and other
cardiovascular death, coronary or carotid revascularization) over 5 years.
RESULTS: Alanine aminotransferase measure had a linear inverse relationship with
the first cardiovascular event occurring in participants during the study period.
After adjustment, for every 1 sd higher baseline alanine aminotransferase measure
(13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4-13; P =
0.02). Participants with alanine aminotransferase levels below and above the
reference range 8-41 U/l for women and 9-59 U/l for men, had hazard ratios for a
cardiovascular event of 1.86 (95% CI 1.12-3.09) and 0.65 (95% CI 0.49-0.87),
respectively (P = 0.001). No relationship was found for gamma
glutamyltransferase. CONCLUSIONS: The data may indicate that in people with Type
2 diabetes, which is associated with higher alanine aminotransferase levels
because of prevalent non-alcoholic fatty liver disease, a low alanine
aminotransferase level is a marker of hepatic or systemic frailty rather than
health.
PMID- 26433208
TI - Use of topical retinoic acid for limbal stem cell failure: a retrospective
clinical case series.
PMID- 26433209
TI - Phaeochromocytoma and ACTH-dependent cushing's syndrome: tumour crf secretion can
mimic pituitary cushing's disease.
AB - INTRODUCTION: 10% of corticotrophin (ACTH)-dependent Cushing's syndrome arises
from secretion by extrapituitary tumours, with phaeochromocytoma implicated in a
few cases. Ectopic secretion by phaeochromocytoma of corticotropin-releasing
hormone (CRF), with secondary corticotroph hyperplasia, is even rarer, with only
five cases in the literature hitherto. However, such cases may be classified as
'ectopic ACTH' due to incomplete verification. CLINICAL CASES: We describe three
patients with phaeochromocytoma and ACTH-dependent Cushing's syndrome in whom
biochemical cure was achieved following unilateral adrenalectomy. Although unable
to access a validated CRF assay within the timeframe for sample storage, we
nevertheless inferred CRF secretion in 2 of 3 cases by tumour immunostaining
(positive for CRF; negative for ACTH), supported in one case by pre-operative
inferior petrosal sinus sampling (IPSS) indicative of pituitary ACTH source. Both
cases were characterized by rapid postoperative wean off glucocorticoids,
presumed to reflect the pituitary stimulatory-effect of CRF outweighing central
negative feedback inhibition by hypercortisolaemia. By contrast, the tumour
excised in a third case exhibited positive immunostaining for ACTH - negative for
CRF - and postoperative recovery of hypothalamic-pituitary-adrenal axis took
significantly longer. DISCUSSION: Ectopic CRF production is biochemically
indistinguishable from ectopic ACTH secretion, except that IPSS mimics pituitary
Cushing's disease and cortisol dynamics may normalize rapidly postadrenalectomy.
CRF secretion can be inferred through tumour immunohistochemistry, even if no CRF
assay is available. Unrecognized phaeochromocytoma ACTH secretion may underpin
some cases of cardiovascular collapse postadrenalectomy through acute
hypocortisolaemia. Despite advances in phaeochromocytoma genetics since previous
reports, we were unable to identify somatic DNA defects associated with either
ACTH or CRF secretion.
PMID- 26433210
TI - beta-Carotene Revisited by Transient Absorption and Stimulated Raman
Spectroscopy.
AB - beta-Carotene in n-hexane was examined by femtosecond transient absorption and
stimulated Raman spectroscopy. Electronic change is separated from vibrational
relaxation with the help of band integrals. Overlaid on the decay of S1 excited
state absorption, a picosecond process is found that is absent when the C9
methyl group is replaced by ethyl or isopropyl. It is attributed to
reorganization on the S1 potential energy surface, involving dihedral angles
between C6 and C9 . In Raman studies, electronic states S2 or S1 were selected
through resonance conditions. We observe a broad vibrational band at 1770 cm(-1)
in S2 already. With 200 fs it decays and transforms into the well-known S1 Raman
line for an asymmetric C=C stretching mode. Low-frequency activity (<800 cm(-1) )
in S2 and S1 is also seen. A dependence of solvent lines on solute dynamics
implies intermolecular coupling between beta-carotene and nearby n-hexane
molecules.
PMID- 26433211
TI - Do dogs sense hypoglycaemia?
AB - AIMS: To summarize the current knowledge on the phenomenon of dogs, both trained
and untrained, sensing hypoglycaemia and alerting their owners to it. METHODS:
Electronic databases were searched for all types of articles reporting on
untrained or trained 'diabetes alert' dogs. Articles published up until December
2014 in the English or German language were included. RESULTS: Several case
reports and observational studies provide evidence that animals can perform at a
level above that attributable to chance, and may reliably detect low diurnal as
well as nocturnal hypoglycaemic episodes. Behavioural changes in untrained dogs
were reported during 38-100% of hypoglycaemic events experienced by their owners.
The sensitivity and specificity of the performance of trained diabetes alert dogs
sensing hypoglycaemia ranged from 22 to 100% and 71 to 90%, respectively.
Additionally, 75-81% of patients with diabetes who owned a trained dog reported a
subsequent improvement in their quality of life. Nevertheless, the available data
are limited and heterogeneous because they rely on low patient numbers and survey
based studies prone to recall bias. CONCLUSION: Further research is needed to
confirm the preliminary data on the reliability and mechanism underlying the
dogs' abilities to detect hypoglycaemia, and its impact on patient outcomes.
PMID- 26433212
TI - Effect of a structured diabetes education programme in primary care on
hospitalizations and emergency department visits among people with Type 2
diabetes mellitus: results from the Patient Empowerment Programme.
AB - AIM: To assess whether a structured diabetes education programme, the Patient
Empowerment Programme, was associated with a lower rate of all-cause
hospitalization and emergency department visits in a population-based cohort of
patients with Type 2 diabetes mellitus in primary care. METHODS: A cohort of 24
250 patients was evaluated using a linked administrative database during 2009
2013. We selected 12 125 patients with Type 2 diabetes who had at least one
Patient Empowerment Programme session attendance. Patients who did not
participate in the Patient Empowerment Programme were matched one-to-one with
patients who did, using the propensity score method. Hospitalization events and
emergency department visits were the events of interest. Cox proportional hazard
and negative binomial regressions were performed to estimate the hazard ratios
for the initial event, and incidence rate ratios for the number of events.
RESULTS: During a median 30.5 months of follow-up, participants in the Patient
Empowerment Programme had a lower incidence of an initial hospitalization event
(22.1 vs 25.2%; hazard ratio 0.879; P < 0.001) and emergency department visit
(40.5 vs 44%; hazard ratio 0.901; P < 0.001) than those who did not participate
in the Patient Empowerment Programme. Participation in the Patient Empowerment
Programme was associated with a significantly lower number of emergency
department visits (incidence rate ratio 0.903; P < 0.001): 40.4 visits per 100
patients annually in those who did not participate in the Patient Empowerment
Programme vs. 36.2 per 100 patients annually in those who did. There were
significantly fewer hospitalization episodes (incidence rate ratio 0.854; P <
0.001): 20.0 hospitalizations per 100 patients annually in those who did not
participate in the Patient Empowerment Programme vs. 16.9 hospitalizations per
100 patients annually in those who did. CONCLUSIONS: Among patients with Type 2
diabetes, the Patient Empowerment Programme was shown to be effective in delaying
the initial hospitalization event and in reducing their frequency.
PMID- 26433213
TI - Short-term and long-term effects of dipeptidyl peptidase-4 inhibitors in type 2
diabetes mellitus patients with renal impairment: a meta-analysis of randomized
controlled trials.
AB - To assess the short-term and long-term effects of dipeptidyl peptidase-4 (DPP-4)
inhibitors in type 2 diabetes mellitus patients with renal impairment, a meta
analysis of randomized clinical trials of DPP-4 inhibitor interventions in type 2
diabetes mellitus patients with renal impairment was performed. PubMed, Embase,
Cochrane Library and ClinicalTrials.gov were searched through the end of March
2015. Randomized clinical trials were selected if (1) DPP-4 inhibitors were
compared with a placebo or other active-comparators, (2) the treatment duration
was >=12 weeks and (3) data regarding changes in haemoglobin A1c (HbA1c ),
changes in fasting plasma glucose or hypoglycaemia and other adverse events were
reported. Of 790 studies, ten studies on eight randomized clinical trials were
included. Compared with the control group, DPP-4 inhibitors were associated with
a greater HbA1c reduction in both the short-term [mean differences (MD) = -0.45,
95% confidence intervals (-0.57, -0.33), p < 0.0001] and long-term [MD = -0.33,
95% confidence intervals (-0.63, -0.03), p = 0.03] treatments. However, the long
term greater reduction in HbA1c with DPP-4 inhibitor treatment was only
significant when the control treatment comprised placebo plus stable background
treatment, but not glipizide plus stable background treatment. DPP-4 inhibitors
were associated with a greater fasting plasma glucose reduction [MD = -12.59, 95%
confidence intervals (-22.01, -3.17), p = 0.009] over the short-term; however,
this effect was not present over the long-term. Regarding the hypoglycaemia
adverse events assessment, the long-term treatment data indicated there was no
increased risk of hypoglycaemia compared with placebo or active-controlled anti
diabetic drugs. The present meta-analysis confirms that DPP-4 inhibitors are
effective and equivalent to other agents in type 2 diabetes mellitus patients
with renal impairment. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26433215
TI - Transcutaneous Skin-Muscle Flap Suspension Lower-Eyelid Blepharoplasty.
PMID- 26433214
TI - Response of colonic motility to dopaminergic stimulation is subverted in rats
with nigrostriatal lesion: relevance to gastrointestinal dysfunctions in
Parkinson's disease.
AB - BACKGROUND: Constipation is extremely common in patients with Parkinson's disease
(PD) and has been described in PD animal models. In this study, we investigated
whether a PD-like degeneration of dopaminergic neurons of the substantia nigra
can influence peristalsis in colonic segments of rats by impacting on enteric
dopaminergic transmission. METHODS: Male, Sprague-Dawley rats received a
unilateral injection of neurotoxin 6-hydroxydopamine (6-OHDA), or saline, into
the medial-forebrain-bundle. Peristaltic activity was recorded in isolated
colonic segments, in baseline conditions and following exposure to combinations
of D2 receptor (DRD2) agonist sumanirole and antagonist L-741626. Dopamine levels
and DRD2 expression were assessed in the ileum and colon of animals. We also
investigated the involvement of the dorsal motor nucleus of the vagus (DMV) - a
potential relay station between central dopaminergic denervation and
gastrointestinal (GI) dysfunction - by analyzing cytochrome c oxidase activity
and FosB/DeltaFosB expression in DMV neurons. KEY RESULTS: We observed profound
alterations in the response of colonic segments of 6-OHDA lesioned animals to
DRD2 stimulation. In fact, the inhibition of colonic peristalsis elicited by
sumanirole in control rats was absent in 6-OHDA-lesioned animals. These animals
also showed reduced DRD2 expression in the colon, along with elevation of
dopamine levels. No significant changes were detected within the DMV. CONCLUSIONS
& INFERENCES: Our results demonstrate that selective lesion of the nigrostriatal
dopaminergic pathway subverts the physiological response of the colon to
dopaminergic stimulation, opening new perspectives in the comprehension and
treatment of GI dysfunctions associated with PD.
PMID- 26433216
TI - Prevalence, Employment Rate, and Cost of Schizophrenia in a High-Income Welfare
Society: A Population-Based Study Using Comprehensive Health and Welfare
Registers.
AB - Schizophrenia is associated with recurrent hospitalizations, need for long-term
community support, poor social functioning, and low employment rates. Despite the
wide- ranging financial and social burdens associated with the illness, there is
great uncertainty regarding prevalence, employment rates, and the societal costs
of schizophrenia. The current study investigates 12-month prevalence of patients
treated for schizophrenia, employment rates, and cost of schizophrenia using a
population-based top-down approach. Data were obtained from comprehensive and
mandatory health and welfare registers in Norway. We identified a 12-month
prevalence of 0.17% for the entire population. The employment rate among working
age individuals was 10.24%. The societal costs for the 12-month period were USD
890 million. The average cost per individual with schizophrenia was USD 106
thousand. Inpatient care and lost productivity due to high unemployment
represented 33% and 29%, respectively, of the total costs. The use of mandatory
health and welfare registers enabled a unique and informative analysis on true
population-based datasets.
PMID- 26433217
TI - Cognitive Effects of High-Frequency rTMS in Schizophrenia Patients With
Predominant Negative Symptoms: Results From a Multicenter Randomized Sham
Controlled Trial.
AB - Cognitive impairments are one of the main contributors to disability and poor
long-term outcome in schizophrenia. Proof-of-concept trials indicate that
repetitive transcranial magnetic stimulation (rTMS) applied to the left
dorsolateral prefrontal cortex (DLPFC) has the potential to improve cognitive
functioning. We analyzed the effects of 10-Hz rTMS to the left DLPFC on cognitive
deficits in schizophrenia in a large-scale and multicenter, sham-controlled
study. A total of 156 schizophrenia patients with predominant negative symptoms
were randomly assigned to a 3-week intervention (10-Hz rTMS, 15 sessions, 1000
stimuli per session) with either active or sham rTMS. The Rey Auditory Verbal
Learning Test, Trail Making Test A and B, Wisconsin Card Sorting Test, Digit Span
Test, and the Regensburg Word Fluency Test were administered before intervention
and at day 21, 45, and 105 follow-up. From the test results, a neuropsychological
composite score was computed. Both groups showed no differences in any of the
outcome variables before and after intervention. Both groups improved markedly
over time, but effect sizes indicate a numeric, but nonsignificant superiority of
active rTMS in certain cognitive tests. Active 10-Hz rTMS applied to the left
DLPFC for 3 weeks was not superior to sham rTMS in the improvement of various
cognitive domains in schizophrenia patients with predominant negative symptoms.
This is in contrast to previous preliminary proof-of-concept trials, but
highlights the need for more multicenter randomized controlled trials in the
field of noninvasive brain stimulation.
PMID- 26433219
TI - Acacetin 7-O-alpha-l-rhamnopyranosyl (1-2) beta-D-xylopyranoside Elicits Life
span Extension and Stress Resistance in Caenorhabditis elegans.
AB - The advancements in the field of gerontology have unraveled the signaling
pathways that regulate life span, suggesting that it might be feasible to
modulate aging. To this end, we isolated a novel phytomolecule Acacetin 7-O-alpha
l-rhamnopyranosyl (1-2) beta-D-xylopyranoside (ARX) from Premna integrifolia and
evaluated its antiaging effects in Caenorhabditis elegans The spectral data
analysis revealed the occurrence of a new compound ARX. Out of the three tested
pharmacological doses of ARX, viz. 5, 25, and 50 uM, the 25-uM dose was able to
extend life span in C. elegans by more than 39%. The present study suggests that
ARX affects bacterial metabolism, which in turn leads to dietary restriction (DR)
like effects in the worms. The effect of ARX on worms with mutations (mev-1, eat
2, sir-2.1, skn-1, daf-16, and hsf-1) indicates that ARX-mediated life-span
extension involves mechanisms associated with DR and maintenance of cellular
redox homeostasis. This study is the first time report on longevity-promoting
activity of ARX in C. elegans mediated by stress and DR-regulating genes. This
novel phytomolecule can contribute in designing therapeutics for managing aging
and age-related diseases.
PMID- 26433220
TI - Reproducibility of the assessment of the Frankel manoeuvre for the evaluation of
sagittal skeletal discrepancies in Class II individuals.
AB - OBJECTIVES: The Frankel manoeuvre is a procedure by which the mandible of Class
II individuals is postured forward in dental Class I relationship. The evaluation
of the resulting facial profile provides information concerning the components
determining the sagittal discrepancy. Data concerning the reproducibility of its
assessment are not available. This study aimed to evaluate the intra-observer and
inter-observer reproducibility of the assessment of the manoeuvre and to assess
whether the amount of clinical experience affects its reproducibility. METHODS:
Two lateral photographs, one in centric occlusion, and the other with the
mandible postured forward (Frankel manoeuvre) of 100 Angle Class II individuals
aged between 9 and 13 years were evaluated by six orthodontists (T0). Each
examiner was asked whether the facial profile worsen or not with the manoeuvre
after being trained by an expert orthodontist. The test was repeated after 2
weeks interval (T1). Intra-observer and inter-observer agreement were evaluated
by computing the Cohen's K. RESULTS: The agreement (K values) between
observations (T0 versus T1) for each examiner ranged from 0.49 to 0.72. The
overall agreement was 0.65 [95% confidence interval (CI) = 0.54-0.75]. The
agreement in the group with less clinical experience was 0.61 (95% CI = 0.46
0.76), while it was 0.68 (95% CI = 0.53-0.83) in the more experienced group. The
amount of clinical experience did not affect intra-observer agreement (P = 0.50).
The overall agreement between the examiners and the trainer was 0.74 (95% CI =
0.65-0.83) and 0.73 (95% CI = 0.64-0.83) at T0 and T1 respectively. CONCLUSION:
The assessment of the Frankel manoeuvre is reproducible and it is not influenced
by the amount of clinical experience.
PMID- 26433218
TI - Pain and Cognitive Function Among Older Adults Living in the Community.
AB - BACKGROUND: Pain related to many age-related chronic conditions is a burdensome
problem in elderly adults and may also interfere with cognitive functioning. The
purpose of this study was to examine the cross-sectional relationship between
measures of pain severity and pain interference and cognitive performance in
community-living older adults. METHODS: We studied 765 participants in the
Maintenance of Balance Independent Living Intellect and Zest (MOBILIZE) Boston
Study, a population-based study of persons aged 70 and older. Global pain
severity and interference were measured using the Brief Pain Inventory subscales.
The neuropsychological battery included measures of attentional capacity (Trail
Making Test A, WORLD Test), executive function (Trail Making Test B and Delta,
Clock-in-a-Box, Letter Fluency), memory (Hopkins Verbal Learning Test), and a
global composite measure of cognitive function. Multivariable linear regression
models were used to analyze the relationship between pain and cognitive
functioning. RESULTS: Elderly adults with more severe pain or more pain
interference had poorer performance on memory tests and executive functioning
compared to elders with none or less pain. Pain interference was also associated
with impaired attentional capacity. Additional adjustment for chronic conditions,
behaviors, and psychiatric medication resulted in attenuation of many of the
observed associations. However, the association between pain interference and
general cognitive function persisted. CONCLUSIONS: Our findings point to the need
for further research to understand how chronic pain may contribute to decline in
cognitive function and to determine strategies that may help in preventing or
managing these potential consequences of pain on cognitive function in older
adults.
PMID- 26433221
TI - ORF8-Related Genetic Evidence for Chinese Horseshoe Bats as the Source of Human
Severe Acute Respiratory Syndrome Coronavirus.
AB - Several lineage B betacoronaviruses termed severe acute respiratory syndrome
(SARS)-like CoVs (SL-CoVs) were identified from Rhinolophus bats in China. These
viruses are characterized by a set of unique accessory open reading frames (ORFs)
that are located between the M and N genes. Among unique accessory ORFs, ORF8 is
most hypervariable. In this study, the ORF8s of all SL-CoVs were classified into
3 types, and, for the first time, it was found that very few SL-CoVs from
Rhinolophus sinicus have ORF8s that are identical to that of human SARS-CoV. This
finding provides new genetic evidence for Chinese horseshoe bats as the source of
human SARS-CoV.
PMID- 26433222
TI - Asymptomatic and Submicroscopic Carriage of Plasmodium knowlesi Malaria in
Household and Community Members of Clinical Cases in Sabah, Malaysia.
AB - Although asymptomatic carriage of human malaria species has been widely reported,
the extent of asymptomatic, submicroscopic Plasmodium knowlesi parasitemia is
unknown. In this study, samples were obtained from individuals residing in
households or villages of symptomatic malaria cases with the aim of detecting
submicroscopic P. knowlesi in this population. Four published molecular assays
were used to confirm the presence of P. knowlesi. Latent class analysis revealed
that the estimated proportion of asymptomatic individuals was 6.9% (95%
confidence interval, 5.6%-8.4%). This study confirms the presence of a
substantial number of asymptomatic monoinfections across all age groups; further
work is needed to estimate prevalence in the wider community.
PMID- 26433223
TI - Hairpins participating in folding of human telomeric sequence quadruplexes
studied by standard and T-REMD simulations.
AB - DNA G-hairpins are potential key structures participating in folding of human
telomeric guanine quadruplexes (GQ). We examined their properties by standard MD
simulations starting from the folded state and long T-REMD starting from the
unfolded state, accumulating ~130 MUs of atomistic simulations. Antiparallel G
hairpins should spontaneously form in all stages of the folding to support
lateral and diagonal loops, with sub-MUs scale rearrangements between them. We
found no clear predisposition for direct folding into specific GQ topologies with
specific syn/anti patterns. Our key prediction stemming from the T-REMD is that
an ideal unfolded ensemble of the full GQ sequence populates all 4096 syn/anti
combinations of its four G-stretches. The simulations can propose idealized
folding pathways but we explain that such few-state pathways may be misleading.
In the context of the available experimental data, the simulations strongly
suggest that the GQ folding could be best understood by the kinetic partitioning
mechanism with a set of deep competing minima on the folding landscape, with only
a small fraction of molecules directly folding to the native fold. The landscape
should further include non-specific collapse processes where the molecules move
via diffusion and consecutive random rare transitions, which could, e.g.
structure the propeller loops.
PMID- 26433224
TI - Acentric chromosome ends are prone to fusion with functional chromosome ends
through a homology-directed rearrangement.
AB - The centromeres of many eukaryotic chromosomes are established epigenetically on
potentially variable tandem repeats; hence, these chromosomes are at risk of
being acentric. We reported previously that artificially created acentric
chromosomes in the fission yeast Schizosaccharomyces pombe can be rescued by end
to-end fusion with functional chromosomes. Here, we show that most
acentric/functional chromosome fusion events in S. pombe cells harbouring an
acentric chromosome I differed from the non-homologous end-joining-mediated
rearrangements that result in deleterious dicentric fusions in normal cells, and
were elicited by a previously unidentified homologous recombination (HR) event
between chromosome end-associated sequences. The subtelomere repeats associated
with the non-fusogenic ends were also destabilized in the surviving cells,
suggesting a causal link between general subtelomere destabilization and
acentric/functional chromosome fusion. A mutational analysis indicated that a non
canonical HR pathway was involved in the rearrangement. These findings are
indicative of a latent mechanism that conditionally induces general subtelomere
instability, presumably in the face of accidental centromere loss events,
resulting in rescue of the fatal acentric chromosomes by interchromosomal HR.
PMID- 26433225
TI - SubtiWiki 2.0--an integrated database for the model organism Bacillus subtilis.
AB - To understand living cells, we need knowledge of each of their parts as well as
about the interactions of these parts. To gain rapid and comprehensive access to
this information, annotation databases are required. Here, we present SubtiWiki
2.0, the integrated database for the model bacterium Bacillus subtilis
(http://subtiwiki.uni-goettingen.de/). SubtiWiki provides text-based access to
published information about the genes and proteins of B. subtilis as well as
presentations of metabolic and regulatory pathways. Moreover, manually curated
protein-protein interactions diagrams are linked to the protein pages. Finally,
expression data are shown with respect to gene expression under 104 different
conditions as well as absolute protein quantification for cytoplasmic proteins.
To facilitate the mobile use of SubtiWiki, we have now expanded it by Apps that
are available for iOS and Android devices. Importantly, the App allows to link
private notes and pictures to the gene/protein pages. Today, SubtiWiki has become
one of the most complete collections of knowledge on a living organism in one
single resource.
PMID- 26433226
TI - BacWGSTdb, a database for genotyping and source tracking bacterial pathogens.
AB - Whole genome sequencing has become one of the routine methods in molecular
epidemiological practice. In this study, we present BacWGSTdb
(http://bacdb.org/BacWGSTdb), a bacterial whole genome sequence typing database
which is designed for clinicians, clinical microbiologists and hospital
epidemiologists. This database borrows the population structure from the current
multi-locus sequence typing (MLST) scheme and adopts a hierarchical data
structure: species, clonal complex and isolates. When users upload the pre
assembled genome sequences to BacWGSTdb, it offers the functionality of bacterial
genotyping at both traditional MLST and whole-genome levels. More importantly,
users are told which isolates in the public database are phylogenetically close
to the query isolate, along with their clinical information such as host,
isolation source, disease, collection time and geographical location. In this
way, BacWGSTdb offers a rapid and convenient platform for worldwide users to
address a variety of clinical microbiological issues such as source tracking
bacterial pathogens.
PMID- 26433227
TI - A cytoplasmic pathway for gapmer antisense oligonucleotide-mediated gene
silencing in mammalian cells.
AB - Antisense oligonucleotides (ASOs) are known to trigger mRNA degradation in the
nucleus via an RNase H-dependent mechanism. We have now identified a putative
cytoplasmic mechanism through which ASO gapmers silence their targets when
transfected or delivered gymnotically (i.e. in the absence of any transfection
reagent). We have shown that the ASO gapmers can interact with the Ago-2 PAZ
domain and can localize into GW-182 mRNA-degradation bodies (GW-bodies). The
degradation products of the targeted mRNA, however, are not generated by Ago-2
directed cleavage. The apparent identification of a cytoplasmic pathway
complements the previously known nuclear activity of ASOs and concurrently
suggests that nuclear localization is not an absolute requirement for gene
silencing.
PMID- 26433228
TI - RPFdb: a database for genome wide information of translated mRNA generated from
ribosome profiling.
AB - Translational control is crucial in the regulation of gene expression and
deregulation of translation is associated with a wide range of cancers and human
diseases. Ribosome profiling is a technique that provides genome wide information
of mRNA in translation based on deep sequencing of ribosome protected mRNA
fragments (RPF). RPFdb is a comprehensive resource for hosting, analyzing and
visualizing RPF data, available at www.rpfdb.org or
http://sysbio.sysu.edu.cn/rpfdb/index.html. The current version of database
contains 777 samples from 82 studies in 8 species, processed and reanalyzed by a
unified pipeline. There are two ways to query the database: by keywords of
studies or by genes. The outputs are presented in three levels. (i) Study level:
including meta information of studies and reprocessed data for gene expression of
translated mRNAs; (ii) Sample level: including global perspective of translated
mRNA and a list of the most translated mRNA of each sample from a study; (iii)
Gene level: including normalized sequence counts of translated mRNA on different
genomic location of a gene from multiple samples and studies. To explore rich
information provided by RPF, RPFdb also provides a genome browser to query and
visualize context-specific translated mRNA. Overall our database provides a
simple way to search, analyze, compare, visualize and download RPF data sets.
PMID- 26433229
TI - SerRS-tRNASec complex structures reveal mechanism of the first step in
selenocysteine biosynthesis.
AB - Selenocysteine (Sec) is found in the catalytic centers of many selenoproteins and
plays important roles in living organisms. Malfunctions of selenoproteins lead to
various human disorders including cancer. Known as the 21st amino acid, the
biosynthesis of Sec involves unusual pathways consisting of several stages. While
the later stages of the pathways are well elucidated, the molecular basis of the
first stage-the serylation of Sec-specific tRNA (tRNA(Sec)) catalyzed by seryl
tRNA synthetase (SerRS)-is unclear. Here we present two cocrystal structures of
human SerRS bound with tRNA(Sec) in different stoichiometry and confirm the
formation of both complexes in solution by various characterization techniques.
We discovered that the enzyme mainly recognizes the backbone of the long variable
arm of tRNA(Sec) with few base-specific contacts. The N-terminal coiled-coil
region works like a long-range lever to precisely direct tRNA 3' end to the other
protein subunit for aminoacylation in a conformation-dependent manner. Restraints
of the flexibility of the coiled-coil greatly reduce serylation efficiencies.
Lastly, modeling studies suggest that the local differences present in the D- and
T-regions as well as the characteristic U20:G19:C56 base triple in tRNA(Sec) may
allow SerRS to distinguish tRNA(Sec) from closely related tRNA(Ser) substrate.
PMID- 26433230
TI - The International Federation of Gynecology and Obstetrics (FIGO) recommendations
on adolescent, preconception, and maternal nutrition: "Think Nutrition First".
PMID- 26433231
TI - Selecting cases for feedback to pre-hospital clinicians - a pilot study.
AB - Background There are currently limited avenues for routine feedback from
hospitals to pre-hospital clinicians aimed at improvements in clinical practice.
Objective The aim of this study was to pilot a method for selectively identifying
cases where there was a clinically significant difference between the pre
hospital and in-hospital diagnoses that could have led to a difference in pre
hospital patient care. Methods This was a single-centre retrospective study
involving cases randomly selected through informatics extraction of final
diagnoses at hospital discharge. Additional data on demographics, triage and
diagnoses were extracted by explicit chart review. Blinded groups of pre-hospital
and in-hospital clinicians assessed data to detect clinically significant
differences between pre-hospital and in-hospital diagnoses. Results Most (96.9%)
patients were of Australasian Triage Scale category 1-3 and in-hospital mortality
rate was 32.9%. Of 353 cases, 32 (9.1%; 95% CI: 6.1-12.1) were determined by both
groups of clinical assessors to have a clinically significant difference between
the pre-hospital and final in-hospital diagnoses, with moderate inter-rater
reliability (kappa score 0.6, 95% CI: 0.5-0.7). Conclusion A modest proportion of
cases demonstrated discordance between the pre-hospital and in-hospital
diagnoses. Selective case identification and feedback to pre-hospital services
using a combination of informatics extraction and clinician consensus approach
can be used to promote ongoing improvements to pre-hospital patient care. What is
known about the topic? Highly trained pre-hospital clinicians perform patient
assessments and early interventions while transporting patients to healthcare
facilities for ongoing management. Feedback is necessary to allow for continual
improvements; however, the provision of formal selective feedback regarding
diagnostic accuracy from hospitals to pre-hospital clinicians is currently not
routine. What does this paper add? For a significant proportion of patients,
there is a clinically important difference in the diagnosis recorded by their pre
hospital clinician compared with their final in-hospital diagnosis. These
clinically significant differences in diagnoses between pre-hospital and in
hospital clinicians were most notable among acute myocardial infarction and
trauma subgroups of patients in this study. What are the implications for
practitioners? Identification of patients who have a significant discrepancy
between their pre-hospital and in-hospital diagnoses could lead to the
development of feedback mechanisms to pre-hospital clinicians. Providing pre
hospital clinicians with this selective feedback would be intended to promote
ongoing improvements in pre-hospital assessments and thereby to improve service
delivery.
PMID- 26433232
TI - The Apprenticeship Model for Surgical Training Is Inferior.
AB - While the apprenticeship model for surgical training is a long-standing gold
standard worldwide, proficiency-based progression (PBP) training proves
significantly superior. The combination of a metrics tool describing procedural
steps and errors with a simulator model or cadaveric training, results in a
measurement tool that not only judges but serves to improve surgeon skill.
PMID- 26433233
TI - Value, Technology, and Our Role As Surgeons: It's Time for a Call to Action.
PMID- 26433234
TI - Synthetic Grafts--Where is the Common Sense?
PMID- 26433235
TI - Authors' Reply.
PMID- 26433236
TI - Regarding "Efficacy of Magnetic Resonance Imaging and Clinical Tests in
Diagnostics of Wrist Ligament Injuries: A Systematic Review".
PMID- 26433237
TI - Author's Reply.
PMID- 26433238
TI - Editorial Commentary: Wrist Ligament Injury Diagnosis.
AB - As also noted regarding the knee, shoulder, and hip, wrist ligament pathology
cannot be ruled out by a negative magnetic resonance imaging. However, while
arthroscopic surgery could be a gold standard for wrist injury diagnosis,
clinically relevant research could consider history, physical examination, and
imaging data in aggregate, rather than focusing solely on an magnetic resonance
imaging interpretation.
PMID- 26433239
TI - Editorial Commentary: Knee Lateral Extra-articular Tenodesis.
AB - Knee lateral extra-articular tenodesis (LET) can be combined with anterior
cruciate ligament (ACL) reconstruction with a goal of reducing anterolateral
rotatory instability. Like double-bundle ACL reconstruction, LET combined with
ACL reconstruction reduces pivot-shift, a subjective test, but results in no
significant difference in clinical outcome.
PMID- 26433240
TI - Editorial Commentary: Knee Hyaluronic Acid Viscosupplementation Reduces
Osteoarthritis Pain.
AB - In contrast to the AAOS knee osteoarthritis guidelines, systematic review of
overlapping meta-analyses shows that viscosupplementation with intra-articular
hyaluronic acid injection reduces knee osteoarthritis pain and improves function
according to the highest level of evidence.
PMID- 26433241
TI - Editorial Commentary: Femoroacetabular Impingement Under-resection Is the Primary
Indication for Revision Arthroscopy.
AB - Complications indicating revision after hip arthroscopy generally manifest within
24 months. Femoroacetabular cam or pincher impingement deformity under-resection
is the primary indication for revision arthroscopy. Revision results in decreased
pain and improved function, and primary and revision hip femoroacetabular
impingement arthroscopic surgeons must be mindful of femoral cam lesion over
resection, which could result in iatrogenic femoral neck fracture.
PMID- 26433242
TI - Editorial Commentary: Rotator Cuff Tears of the Hip.
AB - Abductor muscle tears are the rotator cuff tears of the hip. Arthroscopic or
endoscopic repair results in fewer complications and equal clinical outcomes to
open repair.
PMID- 26433243
TI - A Comparison of K-Wire Versus Screw Fixation on the Outcomes of Distal Phalanx
Fractures.
AB - PURPOSE: To compare K-wire and screw fixation of distal phalanx (DP) fractures
with respect to union and functional outcome. METHODS: This retrospective study
identified patients with DP fractures from a clinic registry taken from 2007 to
2013. Clinical data collected included patient demographics, range of motion
(ROM), removal of implant (ROI), and complications. Radiographic data collected
included fracture type, location, configuration, fracture displacement, and
radiographic union. Statistical analysis was done using a chi-squared test for
categorical variables and paired Student's t test for continuous variables.
RESULTS: A total of 172 patients with DP fractures were seen in our clinic
between 2007 and 2013. Of these, 141 patients were managed conservatively and 31
patients had surgery for 33 DP fractures, of which 12 had K-wire and 21 had screw
fixation. Mean union incidence for screw was 100% compared with 83% for K-wire.
Time to union was 2.4 months for screw fixation compared with 4.1 months for K
wire fixation. ROM for screw fixation was significantly better (60 degrees )
compared with K-wire fixation (45 degrees ). ROM for non-transarticular K-wire
(46 degrees ) was similar to transarticular K-wire (44 degrees ). ROI was
performed in 52% of patients with screw fixation. Other than fingertip
tenderness, which resolved after ROI, no other complications were noted.
CONCLUSIONS: Our study showed that the union incidence and time to union for
screw fixation were comparable to those for K-wire fixation. Screw fixation of DP
fractures resulted in greater distal interphalangeal joint motion compared with K
wire fixation but required removal in half of cases. TYPE OF STUDY/LEVEL OF
EVIDENCE: Therapeutic III.
PMID- 26433244
TI - Transfer of a Terminal Motor Branch Nerve to the Flexor Carpi Ulnaris for Triceps
Reinnervation: Anatomical Study and Clinical Cases.
AB - PURPOSE: To analyze the anatomical feasibility of transferring a motor branch
nerve to the flexor carpi ulnaris (FCU) to the triceps upper medial head motor
branch (UMHM) and to report the resultant outcome of the restoration of elbow
extension in 5 patients with extensive brachial plexus injury. METHODS: The ulnar
and radial nerves were dissected in 10 cadavers. We measured the length and
diameter of the branches to the FCU and the UMHM branch and counted the axons.
Then, 5 male patients, mean age 30 years, underwent FCU nerve branch transfer for
reconstruction of elbow extension. Elbow flexion was restored via a median nerve
branch to biceps transfer. RESULTS: Mean UMHM nerve length and diameter were 86
and 1.5 mm, respectively. Mean number of branches to the FCU muscle was 2.9. Mean
FCU nerve length and diameter were 50 and 1.0 mm, respectively. Mean number of
myelinated fibers was 818 and 743 for the UMHM and the longest branch to the FCU,
respectively. Coaptation between nerves was possible without tension. All
patients recovered functional active elbow extension at a mean follow-up of 19
months with a British Medical Research Council score of M4. After surgery, all
patients retained a functional FCU with a British Medical Research Council score
of M4. CONCLUSIONS: Nonselective ulnar nerve fascicles at the root of the limb
might not be adequate to restore elbow extension when combined with a median
nerve branch transfer for elbow flexion. A selective distal ulnar motor fascicle
such as a FCU motor branch could be harvested and connected to a triceps branch
to restore elbow extension. Such a nerve transfer would also allow for later
transfer of the still functional FCU tendon to the digital extensors. CLINICAL
RELEVANCE: For patients with extensive brachial plexus injury and a preserved
medial cord, transferring a motor branch nerve to the FCU is an effective
technique for the reconstruction of elbow extension. TYPE OF STUDY/LEVEL OF
EVIDENCE: Therapeutic IV.
PMID- 26433245
TI - Operative Treatment of Unstable Long Oblique Proximal Phalanx Fractures.
PMID- 26433246
TI - Clinical and dermoscopic features of combined cutaneous squamous cell carcinoma
(SCC)/neuroendocrine [Merkel cell] carcinoma (MCC).
AB - BACKGROUND: Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma, associated
with Merkel cell polyomavirus. MCC admixed with squamous cell carcinoma (SCC) is
unassociated with polyomavirus, and is genetically distinct. OBJECTIVE: We sought
to distinguish clinically and dermoscopically between MCC and SCC/MCC. METHODS:
We compared patient data for SCC/MCC (n = 26) and MCC (n = 20), and reviewed
clinical and dermoscopic images (n = 9) of SCC/MCC. RESULTS: Patients with
SCC/MCC were older (median 76.5 vs 69 years) and more often male (77% vs 60%),
and had more nonmelanoma skin cancer (85% vs 25%), malignant extracutaneous
tumors (25% vs 5%), lymphoproliferative disorders (23% vs 10%), and
immunodeficient/proinflammatory states (77% vs 35%). In all, 58% of SCC/MCC
versus 10% of MCC were clinically diagnosed nonmelanoma skin cancer. Patients
with SCC/MCC had more metastases (77% vs 40%), more treatment failures (53% vs
45%), shorter survival (41 vs 54 months), and more death from disease (50% vs
40%). SCC/MCC demonstrated marked scale (7/9), and telangiectasia (1/9).
Dermoscopically, small dotted and short linear irregular peripheral vessels and
central milky-red areas with large-diameter arborizing vessels were seen.
LIMITATIONS: The rarity of SCC/MCC limits available data. CONCLUSIONS: SCC/MCC is
aggressive, arising within elderly patients' chronically ultraviolet-exposed
skin, often in the setting of immunosuppression or inflammation. Dermoscopically,
polymorphous vessels in lesions suspicious for nonmelanoma skin cancer are
suggestive.
PMID- 26433248
TI - Trends Form Follows Function: New Ways to Inform and Inspire.
PMID- 26433247
TI - Can oral nonsteroidal antiinflammatory drugs play a role in the prevention of
basal cell carcinoma? A systematic review and metaanalysis.
AB - BACKGROUND: Evidence for an association between aspirin or other nonsteroidal
antiinflammatory drug (NSAID) use and basal cell carcinoma (BCC) has been
inconsistent. OBJECTIVE: We conducted a systematic review and metaanalysis to
assess the effect of oral NSAIDs on BCC. METHODS: PubMed, Web of Science, and
Embase databases were searched up to December 3, 2014. A random effects model
metaanalysis was used to calculate summary estimates of the effects of aspirin,
nonaspirin NSAIDs, or any (aspirin or nonaspirin) NSAID use in patients with BCC.
RESULTS: The summary estimates from 11 studies (1 randomized controlled trial, 5
cohort studies, and 5 case control studies) found a 10% risk reduction of BCC
among those using any NSAID (relative risk [RR], 0.90 [95% confidence interval
{CI}, 0.84-0.97]). A similar but not statistically significant inverse
association was observed for nonaspirin NSAIDs (RR, 0.93 [95% CI, 0.86-1.02]),
while aspirin use was more weakly associated (RR, 0.95 [95% CI, 0.91-1.00]). The
strongest inverse associations were noted among those with either a history of
skin cancers or a high prevalence of actinic keratoses. LIMITATIONS: Dose-effect
estimates could not be calculated because the available data were too
heterogeneous to pool. CONCLUSION: The intake of NSAIDs may help prevent BCC,
particularly in high-risk populations. A large randomized controlled trial is
required to confirm these findings.
PMID- 26433249
TI - New Approaches to Systematics of Trypanosomatidae: Criteria for Taxonomic
(Re)description.
AB - While dixenous trypanosomatids represent one of the most dangerous pathogens for
humans and domestic animals, their monoxenous relatives have frequently become
model organisms for studies of diversity of parasitic protists and host-parasite
associations. Yet, the classification of the family Trypanosomatidae is not
finalized and often confusing. Here we attempt to make a blueprint for future
studies in this field. We would like to elicit a discussion about an updated
procedure, as traditional taxonomy was not primarily designed to be used for
protists, nor can molecular phylogenetics solve all the problems alone. The
current status, specific cases, and examples of generalized solutions are
presented under conditions where practicality is openly favored over rigid
taxonomic codes or blind phylogenetic approach.
PMID- 26433250
TI - Regulation of the Immune Response to alpha-Gal and Vector-borne Diseases.
AB - Vector-borne diseases (VBD) challenge our understanding of emerging diseases.
Recently, arthropod vectors have been involved in emerging anaphylactic diseases.
In particular, the immunoglobulin E (IgE) antibody response to the carbohydrate
Galalpha1-3Galbeta1-(3)4GlcNAc-R (alpha-gal) following a tick bite was associated
with allergies to red meat, cetuximab, and gelatin. By contrast, an anti-alpha
gal IgM antibody response was shown to protect against mosquito-borne malaria.
Herein, we highlight the interplay between the gut microbiota, vectors,
transmitted pathogens, and the regulation of the immune response as a model to
understand the protective or allergic effect of alpha-gal. Establishing the
source of alpha-gal in arthropod vectors and the immune response to vector bites
and transmitted pathogens will be essential for diagnosing, treating, and
ultimately preventing these emerging anaphylactic and other vector-borne
diseases.
PMID- 26433252
TI - The Social Life of African Trypanosomes.
AB - The unicellular parasite Trypanosoma brucei shuttles between its definitive host,
the tsetse fly, and various mammals including humans. In the fly digestive tract,
T. brucei must first migrate to the ectoperitrophic space, establish a persistent
infection of the midgut and then migrate to the salivary glands before being
transmitted to a new mammalian host. In 2010, it was shown that insect stages of
the parasite (procyclic forms) exhibit social motility (SoMo) when cultured on a
semi-solid surface, and it was postulated that this behaviour might reflect a
migration step in the tsetse fly. Now, almost 5 years after the initial report,
several new publications shed some light on the biological function of SoMo and
provide insights into the underlying signalling pathways.
PMID- 26433251
TI - Exosomes and Other Extracellular Vesicles: The New Communicators in Parasite
Infections.
AB - Extracellular vesicles (EVs) have emerged as a ubiquitous mechanism for
transferring information between cells and organisms across all three kingdoms of
life. In addition to their roles in normal physiology, vesicles also transport
molecules from pathogens to hosts and can spread antigens as well as infectious
agents. Although initially described in the host-pathogen context for their
functions in immune surveillance, vesicles enable multiple modes of communication
by, and between, parasites. Here we review the literature demonstrating that EVs
are secreted by intracellular and extracellular eukaryotic parasites, as well as
their hosts, and detail the functional properties of these vesicles in
maturation, pathogenicity and survival. We further describe the prospects for
targeting or exploiting these complexes in therapeutic and vaccine strategies.
PMID- 26433253
TI - Diverse Applications of Environmental DNA Methods in Parasitology.
AB - Nucleic acid extraction and sequencing of genes from organisms within
environmental samples encompasses a variety of techniques collectively referred
to as environmental DNA or 'eDNA'. The key advantages of eDNA analysis include
the detection of cryptic or otherwise elusive organisms, large-scale sampling
with fewer biases than specimen-based methods, and generation of data for
molecular systematics. These are particularly relevant for parasitology because
parasites can be difficult to locate and are morphologically intractable and
genetically divergent. However, parasites have rarely been the focus of eDNA
studies. Focusing on eukaryote parasites, we review the increasing diversity of
the 'eDNA toolbox'. Combining eDNA methods with complementary tools offers much
potential to understand parasite communities, disease risk, and parasite roles in
broader ecosystem processes such as food web structuring and community assembly.
PMID- 26433254
TI - Critical Steps in Protein Export of Plasmodium falciparum Blood Stages.
AB - Plasmodium falciparum blood stages export a large number of proteins into their
host red blood cell, leading to changes to the infected cell that are pivotal for
parasite survival and contribute to parasite virulence. To reach the host cell,
exported proteins follow a multistep pathway that now has been revealed to be
similar for different classes of exported proteins. Here we summarise the current
understanding about the critical segments in protein export of P. falciparum
blood stages and discuss recent findings highlighting protein export as a
potential target for chemotherapeutic interventions.
PMID- 26433255
TI - Temporal patterning of neural synchrony in the basal ganglia in Parkinson's
disease.
PMID- 26433256
TI - Nano-silymarin provides protection against gamma-radiation-induced oxidative
stress in cultured human embryonic kidney cells.
AB - Radiation can produce biological damage, mainly oxidative stress, via production
of free radicals, including reactive oxygen species (ROS). Nanoparticles are of
interest as radioprotective agents, particularly due to their high solubility and
bioavailability. Silymarin is a hepatoprotective agent but has poor oral
bioavailability. Silymarin was formulated as a nanoemulsion with the aim of
improving its bioavailability and therapeutic efficacy. In the present study, we
evaluated self-nanoemulsifying drug delivery systems (SNEDDS) formulated with
surfactants and co-surfactants. Nano-silymarin was characterized by estimating %
transmittance, globule size, and polydispersity index, and by transmission
electron microscopy (TEM). The nano-silymarin obtained was in the range of 3-8nm
diameter. With regard to DNA damage, measured by a plasmid relaxation assay,
maximum protection was obtained at 10MUg/mL. Cytotoxicity of nano-silymarin to
human embryonic kidney (HEK) cells was evaluated using the 3-(4,5-dimethylthiazol
2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Protective efficacy against
gamma-radiation was assessed by reduction in micronucleus frequency and ROS
generation, using the 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) assay.
Radiation-induced apoptosis was estimated by microscopic analysis and cell-cycle
estimation. Nano-silymarin was radioprotective, supporting the possibility of
developing new approaches to radiation protection via nanotechnology.
PMID- 26433257
TI - Effects of soluble and particulate Cr(VI) on genome-wide DNA methylation in human
B lymphoblastoid cells.
AB - Several previous studies highlighted the potential epigenetic effects of Cr(VI),
especially DNA methylation. However, few studies have compared the effects of
Cr(VI) on DNA methylation profiles between soluble and particulate chromate in
vitro. Accordingly, Illumina Infinium Human Methylation 450K BeadChip array was
used to analyze DNA methylation profiles of human B lymphoblastoid cells exposed
to potassium dichromate or lead chromate, and the cell viability was also
studied. Array based DNA methylation analysis showed that the impacts of Cr(VI)
on DNA methylation were limited, only about 40 differentially methylated CpG
sites, with an overlap of 15CpG sites, were induced by both potassium dichromate
and lead chromate. The results of mRNA expression showed that after Cr(VI)
treatment, mRNA expression changes of four genes (TBL1Y, FZD5, IKZF2, and
KIAA1949) were consistent with their DNA methylation alteration, but DNA
methylation changes of other six genes did not correlate with mRNA expression. In
conclusion, both of soluble and particulate Cr(VI) could induce a small amount of
differentially methylated sites in human B lymphoblastoid cells, and the
correlations between DNA methylation changes and mRNA expression varied between
different genes.
PMID- 26433258
TI - The effect of gamma radiation on the Common carp (Cyprinus carpio): In vivo
genotoxicity assessment with the micronucleus and comet assays.
AB - Radioactive wastes may be leached into freshwater, either accidentally or in
industrial effluents. We have studied gamma radiation-induced DNA damage in the
freshwater fish Cyprinus carpio. Fish were irradiated with 2-10Gy gamma radiation
and genotoxic effects in blood cells were studied with the micronucleus (MN) and
comet assays. Micronuclei and a dose-dependent increase in comet-tail DNA were
seen in dose- and time-dependent studies. The highest % tail DNA was observed at
24h, declining until 72h, which may indicate the repair of radiation-induced DNA
single-strand breaks after gamma radiation. However, double-stranded DNA damage
may not have been repaired, as indicated by increased micronuclei at later
periods. A positive correlation was observed between the comet and micronucleus
assay results. This study confirms the mutagenic/genotoxic potential of gamma
radiation in the Common carp, as well as the possible combined use of the
micronucleus and comet assays for in vivo laboratory studies with fresh-water
fish for screening the genotoxic potential of radioactive pollution.
PMID- 26433259
TI - Radiation sensitivity of the gastrula-stage embryo: Chromosome aberrations and
mutation induction in lacZ transgenic mice: The roles of DNA double-strand break
repair systems.
AB - At the gastrula phase of development, just after the onset of implantation, the
embryo proper is characterized by extremely rapid cell proliferation. The
importance of DNA repair is illustrated by embryonic lethality at this stage
after ablation of the genes involved. Insight into mutation induction is called
for by the fact that women often do not realize they are pregnant, shortly after
implantation, a circumstance which may have important consequences when women are
subjected to medical imaging using ionizing radiation. We screened gastrula
embryos for DNA synthesis, nuclear morphology, growth, and chromosome aberrations
(CA) shortly after irradiation with doses up to 2.5Gy. In order to obtain an
insight into the importance of DNA repair for CA induction, we included mutants
for the non-homologous end joining (NHEJ) and homologous recombination repair
(HRR) pathways, as well as Parp1-/- and p53+/- embryos. With the pUR288 shuttle
vector assay, we determined the radiation sensitivity for point mutations and
small deletions detected in young adults. We found increased numbers of abnormal
nuclei 5h after irradiation; an indication of disturbed development was also
observed around this time. Chromosome aberrations 7h after irradiation arose in
all genotypes and were mainly of the chromatid type, in agreement with a cell
cycle dominated by S-phase. Increased frequencies of CA were found for NHEJ and
HR mutants. Gastrula embryos are unusual in that they are low in exchange
induction, even after compromised HR. Gastrula embryos were radiation sensitive
in the pUR288 shuttle vector assay, giving the highest mutation induction ever
reported for this genetic toxicology model. On theoretical grounds, a delayed
radiation response must be involved. The compromised developmental profile after
doses up to 2.5Gy likely is caused by both apoptosis and later cell death due to
large deletions. Our data indicate a distinct radiation-sensitive profile of
gastrula embryos, including some stage-specific aspects that are not as yet
understood.
PMID- 26433260
TI - Ameliorative effects of N-acetylcysteine on fluoride-induced oxidative stress and
DNA damage in male rats' testis.
AB - This study was to elucidate DNA damage in rats treated with sodium fluoride (NaF)
by performing 8-Hydroxy-2-deoxyguanosine (8-OHdG) immunohistochemical staining
assays on seminiferous tubules of rats' testis, and also to evaluate the
protective effects of N-acetylcysteine (NAC) on spermatogenesis. Male Sprague
Dawley (SD) rats were exposed to a single dose of NaF (25mg/kg/day) with or
without NAC (150mg/kg/day) for 7 weeks (7W) by gastric gavage. Testicular
fluorine content was detected by fluorine ion selective electrode method.
Oxidative damage to DNA was evaluated by measuring the increase in 8-OHdG
formation in testicular tissue through immunohistochemical staining assays and
also the effects of NAC pretreatment. The biochemical indicators about oxidative
stress were detected by colorimetric assays, sperm parameters and the
morphological changes of testis were studied. NaF significantly increased serum
levels of oxidative stress, markedly elevated testicular fluorine and 8-OHdG
expression levels as well as the rate of sperm aberration compared to saline
group. Testosterone in serum, sperm counts and the mobility of sperm were lower
than those of the rats in control group. The pathological morphological changes
in testicular seminiferous tubule were also obvious in the rats with NaF
treatment. Pretreatment with NAC did not reduce the contents of fluoride content
in testis, but significantly reduced 8-OHdG formation and lipid peroxidation.
This study suggests that NAC may have certain antagonism on the reproductive
damage induced by NaF.
PMID- 26433261
TI - Does the crystal habit modulate the genotoxic potential of silica particles? A
cytogenetic evaluation in human and murine cell lines.
AB - Crystalline silica inhaled from occupational sources has been classified by IARC
as carcinogenic to humans; in contrast, for amorphous silica, epidemiological and
experimental evidence remains insufficient. The genotoxicity of crystalline
silica is still debated because of the inconsistency of experimental results
("variability of silica hazard"), often related to the features of the particle
surfaces. We have assessed the role of crystal habit in the genotoxicity of
silica powders. Pure quartz (crystalline) and vitreous silica (amorphous),
sharing the same surface features, were used in an in vitro study with human
pulmonary epithelial (A549) and murine macrophage (RAW264.7) cell lines,
representative of occupational and environmental exposures. Genotoxicity was
evaluated by the comet and micronucleus assays, and cytotoxicity by the trypan
blue method. Cells were treated with silica powders for 4 and 24h. Quartz but not
vitreous silica caused cell death and DNA damage in RAW264.7 cells. A549 cells
were relatively resistant to both powders. Our results support the view that
crystal habit per se plays a pivotal role in modulating the biological responses
to silica particles.
PMID- 26433262
TI - Dominant lethal mutation test in male mice exposed to 900MHz radiofrequency
fields.
AB - Adult male ICR mice were exposed to continuous wave 900MHz radiofrequency fields
(RF) at 1.6mW/cm(2) power intensity (whole body average specific absorption rate
of 0.731W/kg) for 4 hour/day for 15 days. At the end of exposure, each mouse was
caged with 3 mature virgin female mice for mating. After 7 days, each male mouse
was transferred to a fresh cage and mated with a second batch of 3 females. This
process was repeated for a total of 4 consecutive weeks. Sham exposed male mice
and those subjected to an acute 2Gy gamma-irradiation (GR) were handled similarly
and used as un-exposed and positive controls, respectively. All females were
sacrificed on the 18th day of gestation and presumptive mating and, the contents
in their uteri were examined. The overall observations during the 4 weeks of
mating indicated that the un-exposed female mice mated to RF-exposed male mice
showed no significant differences in the percentage of pregnancies, total
implants, live implants and dead implants when compared with those mated with
sham-exposed mice. In contrast, female mice mated with GR-exposed males showed a
consistent pattern of significant differences in the above indices in each and
all 4 weeks of mating. Thus, the data indicated an absence of mutagenic potential
of RF exposure in the germ cells of male mice.
PMID- 26433263
TI - Graphene oxide/polyethyleneglycol composite coated stir bar for sorptive
extraction of fluoroquinolones from chicken muscle and liver.
AB - Graphene oxide (GO) is an ideal adsorbent for polar and less polar compounds due
to its hexagonal carbon network structure with oxygen-containing groups, while
its strong hydrophilicity and water solubility limited its application in sample
pretreatment techniques. Herein, GO was composited with polyethyleneglycol (PEG)
or polyaniline (PAN) through intermolecular interactions to improve its
stability, and the GO/PEG and GO/PAN composite coated stir bars were prepared by
sol-gel technique. Compared with GO/PAN composite and polydimethylsiloxane (PDMS)
coated stir bar, the prepared GO/PEG composite coated stir bar exhibited higher
extraction efficiency for five fluoroquinolones (FQs). Based on it, a method of
GO/PEG composite coated stir bar sorptive extraction (SBSE) combined with high
performance liquid chromatography-fluorescence detector (HPLC-FLD) was proposed.
The factors influencing SBSE, such as sample pH, salt effect, stirring rate,
extraction time, desorption solvent and desorption time, were optimized, and the
analytical performance of the developed SBSE-HPLC-FLD method was evaluated. The
limits of detection (LODs) for five FQs were in the range of 0.0045-0.0079MUgL(
1), and the enrichment factors (EFs) were in the range of 41.5-65.5-fold
(theoretical enrichment factor was 100-fold). The reproducibility was also
investigated at concentrations of 0.05MUgL(-1) and the relative standard
deviations (RSDs, n=6) were found to be in the range of 4.6-12.1%. The proposed
method was successfully applied for the determination of FQs in chicken muscle
and chicken liver samples.
PMID- 26433264
TI - Comparison of nano and conventional liquid chromatographic methods for the
separation of (+)-catechin-ethyl-malvidin-3-glucoside diastereoisomers.
AB - Nano-liquid chromatography and conventional HPLC were used for the separation of
diastereomers of (+)-catechin-ethyl-malvidin-3-glucoside. Those bridged
anthocyanin dyes were obtained by reaction of (+)-catechin with malvidin-3
glucoside in the presence of acetaldehyde. Both diastereomers were isolated with
semipreparative chromatography and their structures were confirmed by nuclear
magnetic resonance and mass spectrometry. In-laboratory prepared capillary
columns packed with fully porous particles Chromosphere C18, dp=3MUm, core-shell
particles Kinetex C18, dp=2.6MUm (100MUm i.d.) and monolithic column Chromolith
CapRod (100MUm i.d.) were used for the separation of (+)-catechin, malvidin-3
glucoside and both diastereomers. Chromosphere C18 stationary phase provided the
best chromatographic performance. Mobile phase containing water:acetonitrile
(80:20) acidified with trifluoroacetic acid (0.1%, v/v/v) was used in an
isocratic elution mode with a flow rate of 360nLmin(-1). Separation of studied
compounds was achieved in less than 7min under optimized conditions. The nano
liquid chromatographic method and a conventional HPLC one using the same fully
porous particles (Chromosphere C18, 3MUm, 100mm*4.6mm) were compared providing
higher separation efficiency with the first analytical method and similar
selectivity. A better peak symmetry and higher resolution of the studied
diastereomers was achieved by conventional chromatography. Nevertheless, nano
liquid chromatography appeared to be useful for the separation of complex
anthocyanin dyes and can be utilized for their analysis in plant and food micro
samples. The developed method was used for analysis of red wine grape pomace.
PMID- 26433265
TI - Tadpole toxicity prediction using chromatographic systems.
AB - Toxicity has been emulated in tadpole species through chromatographic systems.
The parameter studied to evaluate the non-specific toxicity of a compound is the
narcosis concentration (Cnar), which is defined as the concentration needed for
the immobilization of the organism. Because experimental investigation with
animals is lengthy, costly, technically difficult, and ethically questionable,
there is a great interest in developing surrogate physicochemical systems able to
emulate biological systems to obtain the same information in a faster, more
economic, and easier manner. In order to see which chromatographic systems would
be able to emulate tadpole narcosis, both, tadpole narcosis data and data in
several chromatographic and electrophoretic systems, were fitted to a linear
solvation energy relationship (LSER) model. Thus, by comparison of the models it
was possible to see which of the chromatographic systems were more similar to the
biological one. The physicochemical systems that best emulate tadpole narcosis
were an HPLC system based on an immobilized artificial membrane (IAM) column, and
two micellar electrokinetic chromatography (MEKC) systems based on sodium
taurocholate (STC) and a mixture of sodium dodecylsulphate (SDS) and Brij 35 as
surfactants. A system based on a RP18 HPLC column also was selected for
comparison because it is a common column in most analytical laboratories. To
establish the models, a set of compounds with known Cnar values were analyzed in
the chromatographic, and electrophoretic selected systems and, then, the
retention factor (k) was correlated to the concentration of narcosis. Statistics
showed that the system based on STC micelles was the best to emulate toxicity in
tadpoles. The robustness and predictive ability of the developed models were
validated.
PMID- 26433266
TI - Development of a subcritical water extraction approach for trace analysis of
chloramphenicol, thiamphenicol, florfenicol, and florfenicol amine in poultry
tissues.
AB - Subcritical water extraction was investigated as a novel and alternative
technology for the separation of trace amounts of chloramphenicol, thiamphenicol,
florfenicol and its major metabolite florfenicol amine from poultry tissues and
its results were compared with those of conventional shaking extraction,
ultrasonic extraction, and pressurized liquid extraction. Decreasing the polarity
of water by successively increasing the extraction temperature from 50 degrees C
to 200 degrees C at the moderate pressure enabled selective, highly effective
extractions to be performed. Rapid quantification of the target compounds was
carried out by ultra-performance liquid chromatography coupled with electrospray
ionization tandem mass spectrometry (UPLC-ESI-MS/MS). The critical parameters of
subcritical water extraction such as solvent modifier, temperature, pressure,
extraction time, and static cycles were varied with control. The optimized
extraction procedures using subcritical water as extraction solvent, were carried
out on a pressurized liquid extractor operated at 150 degrees C and 100bar,
applying two static cycles for 3min. Average recoveries of the four analytes from
fortified samples ranged between 86.8% and 101.5%, with relative standard
deviations (RSDs) lower than 7.7%. The limits of detection (LODs) and
quantification (LOQs) for the target compounds were in the ranges of 0.03
0.5MUgkg(-1) and 0.1-2.0MUgkg(-1), respectively. The proposed method is fast,
sensitive, water-based thus more environmental acceptable, making it a suitable
replacement for conventional organic solvent extraction in veterinary drug
residue analysis.
PMID- 26433267
TI - Effect of gestational antiandrogen treatment on Dicer1 expression in the porcine
fetal gonads.
AB - Recently, we have demonstrated that flutamide-induced androgen deficiency during
fetal life led to changes in gene expression that affected both testicular
functions and follicular formation. It is known that microRNA-mediated genes
regulation is essential for gonadal development and function. Thus, the aim of
the present study was to examine whether prenatal flutamide exposure influences
expression of Dicer1, an enzyme involved in microRNA maturation, in gonads of
porcine fetuses during mid- and late gestation. Pregnant gilts were injected with
flutamide (50mg/day/kg b.w.) or corn oil (controls) between days 43-49, 83-89 or
101-107 of gestation. The fetal gonads were obtained on gestational day 50
(GD50), 90 (GD90) or 108 (GD108). To assess Dicer1 mRNA expression real-time PCR
were performed. Furthermore, immunohistochemical Dicer1 localization was
conducted. In testes from flutamide treated fetuses, increased Dicer1 mRNA
expression was observed in the GD50 and GD108 groups, but decreased in the GD90
group. Dicer1 was immunolocalized in the fetal Leydig cells in both control and
flutamide-treated groups. In fetal ovaries, antiandrogen treatment increased
Dicer1 mRNA level in the GD50 and GD90 groups. In control and flutamide-exposed
groups, Dicer1 was localized in the germ cells within oogonia/oocyte nests as
well as in the granulosa cells and oocytes of forming follicles. Concluding,
diminished androgen action during gestation induces changes in Dicer1 mRNA
expression, which may affect post-transcriptional gene regulation via miRNAs in
porcine fetal gonads. However, it seems that androgens exert diverse biological
effects depending on the gestational period.
PMID- 26433268
TI - Chronic stress and antidepressant induced changes in Hdac5 and Sirt2 affect
synaptic plasticity.
AB - Changes in histone acetylation could contribute to the pathogenesis of depression
and antidepressant therapy. Using the chronic social defeat stress (CSDS) model
of depression and different antidepressant treatments we studied the regulation
of histone deacetylases (Hdac's) and synaptic plasticity markers in the
prefrontal cortex (PFC). Further, functional implication of identified Hdac's in
brain plasticity was explored. Mice were exposed to CSDS (10 days) followed by
saline or imipramine (4 weeks). PFC Hdac's mRNA abundance was studied and
compared to human's. Further, protein expression of acetylated histones (AcH3 and
AcH4), neuroplasticity markers (CREB and pro-BDNF) and selected Hdac's were
analyzed. Moreover, other antidepressants (fluoxetine and reboxetine) and
selective HDAC inhibitors were studied. CSDS increased Hdac5 and Sirt2 mRNA
whereas repeated imipramine did the opposite. Accordingly, stress and imipramine
induced opposite changes on AcH3, AcH4 and CREB expression. At protein level,
CSDS upregulated nuclear fraction of Hdac5 and repeated imipramine and reboxetine
increased its phosphorylated form (p-Hdac5), mainly located in the cytoplasm.
Moreover, Sirt2 was downregulated by all monoaminergic antidepressants. Further,
repeated treatment with the class IIa Hdac inhibitor MC1568 and the Sirt2
inhibitor 33i for three weeks increased synaptic plasticity in the prefrontal
cortex. Our results suggest that Hdac5 and Sirt2 upregulation could constitute
stable stress-induced neuronal adaptations. Noteworthy, the SIRT2 upregulation in
depressed patients supports the interest of this target for therapeutic
intervention. On the other hand, cytoplasmic Hdac5 export and Sirt2
downregulation induced by monoaminergic antidepressants could contribute to the
well-known beneficial effects of antidepressants on brain plasticity.
PMID- 26433269
TI - Familial Incidence of Cardiovascular Malformations in Hypoplastic Left Heart
Syndrome.
AB - Obstructive left-sided congenital heart lesions exhibit familial clustering, and
familial echocardiographic screening for bicuspid aortic valve has become
standard practice. Hypoplastic left heart syndrome (HLHS) is a severe left-sided
obstructive lesion; however, familial screening is not universally recommended.
The purpose of this study was to define the incidence of cardiovascular
malformations (CVMs) in first-degree relatives of HLHS probands. First-degree
relatives were screened for CVM by transthoracic echocardiography. Screening was
completed in 152 family members (97 parents and 55 siblings) of 52 probands. Of
these, 17 of 152 (11%) had CVM. Anomalies detected included: bicuspid aortic
valve in 5 (3%), isolated dilated ascending aorta in 4 (3%), coarctation of the
aorta in 1, partial anomalous pulmonary venous connection in 1, anomalous,
intramural coronary artery in 1, bicuspid pulmonary valve in 1, and other
anomalies in 4. Most were previously undiagnosed (11 of 17, 65%). Fourteen of 52
families (27%) had >=1 relative with CVM. Overall, 7 of 55 siblings (13%), 5 of
46 fathers (11%) and 5 of 51 mothers (10%) had CVM. Although the incidence of CVM
in first-degree relatives of HLHS probands was lower in this cohort than
previously reported, it remained substantial, with at least one additional member
having CVM in 27% of families. The frequent occurrence of undiagnosed CVM
highlights the importance of routine familial screening in HLHS. In fact, even if
screening was done in childhood, it may be appropriate to screen again in the
third or fourth decade to exclude isolated enlargement of the ascending aorta.
PMID- 26433270
TI - Immediate and Long-Term Results of Drug-Eluting Stents in Mammary Artery Grafts.
AB - Percutaneous intervention of a coronary graft is the treatment of choice when the
graft fails. The objective is to report the long-term results of drug-eluting
stents (DES) in mammary artery grafts (MAG). Patients who had been treated with
DES for MAG in 27 centers were selected. The baseline and procedural clinical
data were included prospectively, and the follow-up was performed with the
patients, families, and medical records. Two hundred and sixty-eight patients
were included: age 65.5 +/- 10.1 years, diabetes 47.8%, ejection fraction 55.5 +/
14.9%. INDICATION: stable angina 28.4%, unstable angina 38.1%, non-ST-elevation
myocardial infarction 21.6%, ST-elevation myocardial infarction 5.3%, and heart
failure 6.7%; 1.19 +/- 0.59 stents/patient were implanted measuring 18.8 +/- 8.8
mm in length and 2.68 +/- 0.35 mm in diameter. Rapamycin was used in 78 cases
(29.1%), paclitaxel in 77 (28.7%), everolimus in 70 (26.1%), zotarolimus in 34
(12.7%), and biolimus in 9 (3.4%). All cases were successful except for 1 in
which the patient died 30 minutes after the procedure. There were no other
inhospital events. After a follow-up of 41 months (Q25: 23.7 to Q75: 57.8), 24
patients (9%) died of heart-related causes and 20 (7.5%) of noncardiac causes.
Repeat revascularization was necessary in 31 cases, and in 1 additional patient,
there was total occlusion, which was not treated. These 32 patients represented
11.9% of the total. In conclusion, the implantation of DES in MAG shows very high
procedural success and also low long-term event rates.
PMID- 26433271
TI - What do grade school students and physicians have in common?
PMID- 26433272
TI - Usefulness of the Left Anterior Descending Coronary Artery Wrapping Around the
Left Ventricular Apex to Predict Adverse Clinical Outcomes in Patients With
Anterior Wall ST-Segment Elevation Myocardial Infarction (from the Harmonizing
Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial).
AB - The association between anatomic features of the left anterior descending artery
(LAD) and outcomes in patients with anterior ST-segment elevation myocardial
infarction (STEMI) has not been fully investigated. We sought to clarify the
impact of an LAD coronary artery wrapping around the left ventricular (LV) apex
on clinical outcomes in patients with anterior STEMI. Harmonizing Outcomes with
Revascularization and Stents in Acute Myocardial Infarction enrolled patients
with STEMI presenting <12 hours after symptom onset who underwent primary
percutaneous coronary intervention. Patients with a culprit lesion in the LAD
were categorized as (1) LAD wrapping around the LV apex (wrap-around LAD, n =
871) versus (2) LAD not wrapping around the LV apex (non-wrap-around LAD, n =
224). Killip class >=II, dysrhythmia, and LV mural thrombi were more frequently
observed in the wrap-around LAD group; LV ejection fraction was worse in the wrap
around LAD group (54.5% vs 58.7%, p = 0.006). At 3 years of follow-up, major
adverse cardiac events (death, stroke, or stent thrombosis, 12.7% vs 5.4%, p =
0.002), death (6.6% vs 3.2%, p = 0.052), stroke (1.9% vs 0.5%, p = 0.12), stent
thrombosis (5.6% vs 2.3%, p = 0.047), and severe heart failure (4.5% vs 1.4%, p =
0.03) were more common in patients with a wrap-around LAD versus those with a non
wrap-around LAD. Multivariate analysis indicated that a wrap-around LAD
independently and significantly predicted major adverse cardiac events (hazard
ratio 2.18, p = 0.02) and severe heart failure (odds ratio 3.31, p = 0.049) in
patients with an anterior STEMI. In conclusion, a wrap-around LAD predicted
adverse clinical outcomes at 3 years in patients with anterior STEMI who
underwent primary percutaneous coronary intervention.
PMID- 26433274
TI - Usefulness of Coronary Atheroma Burden to Predict Cardiovascular Events in
Patients Presenting With Acute Coronary Syndromes (from the PROSPECT Study).
AB - We investigated the relation between overall atheroma burden and clinical events
in the Providing Regional Observations to Study Predictors of Events in the
Coronary Tree (PROSPECT) study. In PROSPECT, 660 patients (3,229 nonculprit
lesions with a plaque burden >= 40% and complete intravascular ultrasound data)
were divided into tertiles according to baseline percent atheroma volume (PAV:
total plaque/vessel volume). Patients were followed for 3.4 years (median); major
adverse cardiac events (MACE: death from cardiac causes, cardiac arrest,
myocardial infarction, or rehospitalization because of unstable or progressive
angina) were adjudicated to either culprit or nonculprit lesions. Compared with
patients in low or intermediate PAV tertiles, patients in the high PAV tertile
had the greatest prevalence of plaque rupture and radiofrequency thin-cap
fibroatheroma (VH-TCFA) and the highest percentage of necrotic core volume; they
were also more likely to have high-risk lesion characteristics: >= 1 lesion with
minimal luminal area <= 4 mm(2), plaque burden >70%, and/or VH-TCFA. Three-year
cumulative nonculprit lesion-related MACE was greater in the intermediate and
high tertiles than in the low tertile (6.3% vs 14.7% vs 15.1%, low vs
intermediate vs high tertiles, p = 0.009). On Cox multivariable analysis, insulin
dependent diabetes (hazard ratio [HR] 3.98, p = 0.002), PAV (HR 1.06, p = 0.03),
and the presence of >=1 VH-TCFA (HR 1.80, p = 0.02) were independent predictors
of nonculprit MACE. In conclusion, increasing baseline overall atheroma burden
was associated with more advanced, complex, and vulnerable intravascular
ultrasound lesion morphology and independently predicted nonculprit lesion
related MACE in patients with acute coronary syndromes after successful culprit
lesion intervention.
PMID- 26433273
TI - Relation of Pre-anthracycline Serum Bilirubin Levels to Left Ventricular Ejection
Fraction After Chemotherapy.
AB - Myocardial injury because of oxidative stress manifesting through reductions in
left ventricular ejection fraction (LVEF) may occur after the administration of
anthracycline-based chemotherapy (A-bC). We hypothesized that bilirubin, an
effective endogenous antioxidant, may attenuate the reduction in LVEF that
sometimes occurs after receipt of A-bC. We identified 751 consecutively treated
patients with cancer who underwent a pre-A-bC LVEF measurement, exhibited a serum
total bilirubin level <2 mg/dl, and then received a post-A-bC LVEF assessment
because of symptomatology associated with heart failure. Analysis of variance,
Tukey's Studentized range test, and chi-square tests were used to evaluate an
association between bilirubin and LVEF changes. The LVEF decreased by 10.7 +/-
13.7%, 8.9 +/- 11.8%, and 7.7 +/- 11.5% in group 1 (bilirubin at baseline <=0.5
mg/dl), group 2 (bilirubin 0.6 to 0.8 mg/dl), and group 3 (bilirubin 0.9 to 1.9
mg/dl), respectively. More group 1 patients experienced >15% decrease in LVEF
compared with those in group 3 (p = 0.039). After adjusting for age, coronary
artery disease/myocardial infarction, diabetes mellitus, hematocrit, and the use
of cardioactive medications, higher precancer treatment bilirubin levels and
lesser total anthracycline doses were associated with LVEF preservation (p =
0.047 and 0.011, respectively). In patients treated with anthracyclines who
subsequently develop symptoms associated with heart failure, pre-anthracycline
treatment serum bilirubin levels inversely correlate with subsequent
deterioration in post-cancer treatment LVEF. In conclusion, these results suggest
that increased levels of circulating serum total bilirubin, an intrinsic
antioxidant, may facilitate preservation of LVEF in patients receiving A-bC for
cancer.
PMID- 26433275
TI - Comparison of Outcomes of Transfemoral Transcatheter Aortic Valve Implantation
Using a Minimally Invasive Versus Conventional Strategy.
AB - Some centers, mostly in Europe, have demonstrated the feasibility of a minimally
invasive strategy (MIS; i.e., local anesthesia and conscious sedation, performed
in the cath laboratory without transesophageal echocardiography guidance).
Nonetheless, the experience of MIS for TAVI using both commercially available
valves is lacking in the United States. We, therefore, retrospectively studied
all transfemoral TAVI cases performed at our institution between March 2011 and
November 2014 to assess the safety and efficacy of MIS. Patients were
dichotomized according to the strategy (MIS vs conventional strategy [CS]) used
for the procedure. One hundred sixteen patients were included in the MIS group
and 91 patients were included in the CS group. Baseline characteristics were
similar, and procedural success was comparable (99.1% in MIS and 98.9% in CS, p =
1). One intraprocedural death occurred in each group, whereas conversion rates to
general anesthesia were low (3.4%). Comparable device success was obtained. Rates
of complications and >mild paravalvular leak before discharge were low and
comparable. Length of hospital stay was significantly reduced in the MIS (median,
3.0 [2.0 to 5.0] days) compared with than that in CS group (median 6.0 days [3.5,
8.0]). At a median follow-up of 230 days, no significant difference in survival
rate was detected (89% vs 88%, p = 0.9). On average, MIS was associated with
remarkable cost saving compared with CS ($16,000/case). In conclusion, TAVI
through MIS was associated with a shorter postprocedural hospital stay, lower
costs, and similar safety profile while keeping procedural efficacy compared with
CS.
PMID- 26433276
TI - Prevalence of diabetes mellitus in patients With Takotsubo syndrome.
PMID- 26433277
TI - Clinical Outcome and Cost Analysis of Sutureless Versus Transcatheter Aortic
Valve Implantation With Propensity Score Matching Analysis.
AB - Surgical sutureless and interventional transcatheter aortic valve prostheses are
nowadays extensively adopted in high-risk elderly patients. An explorative
analysis was carried out to compare the clinical outcome and costs associated to
these approaches. Since 2010, a total of 626 patients were distributed between
transcatheter aortic valve implantation (TAVI; n = 364) and sutureless (n = 262)
groups. Patients of both groups were not comparable for clinical and surgical
characteristics, but many patients were in a "gray zone"; therefore, a
retrospective propensity score analysis was possible and performed. For the
matched pair samples, postoperative, follow-up clinical data, and costs data were
obtained. In-hospital death occurred in 5 patients in sutureless group and 3
patients in TAVI group (p = 0.36). Blood transfusions were higher in sutureless
group (2.1 +/- 2.3 vs 0.4 +/- 1.0 U). TAVI group had a shorter intensive care
unit and hospital stay (2.2 +/- 2.7 vs 3.2 +/- 3.5 days, p = 0.037; 12 +/- 6 vs
14 +/- 6 days, p = 0.017). No differences in postoperative neurologic (p =
0.361), renal (p = 0.106), or respiratory (p = 0.391) complications were observed
between groups. At follow-up (24.5 +/- 13.8 months), 1 patient in sutureless
group and 7 patients in TAVI group died (p = 0.032). Paravalvular leakage
occurred more frequently in patients in TAVI group (35 [34%] vs 7 [6.9%]; p
<0.001) with an impact on follow-up survival rate. The costs associated to the 2
procedures are similar when the cost of the device was excluded (p = 0.217). When
included, the sutureless approach resulted a cost saving (?22,451 vs ?33,877, p
<0.001). In conclusion, the patients in the "gray zone" record a satisfying
clinical outcome after sutureless surgery and TAVI. Patients in the sutureless
group endure more hospital complications, but TAVI entails a higher follow-up
mortality. On the costs aspects, TAVI technologies are more expensive, and it
reflects on higher overall hospital costs.
PMID- 26433278
TI - Preface.
PMID- 26433279
TI - Thirty years of progress in harmonizing and compiling food data as a result of
the establishment of INFOODS.
AB - The International Network of Foods Data Systems (INFOODS) has provided leadership
on the development and use of food composition data for over 30years. The mission
of INFOODS is the promotion of international participation, cooperation and
harmonization in the generation, compilation and dissemination of adequate and
reliable data on the composition of foods, beverages, and their ingredients in
forms appropriate to meet the needs of various users. Achievements include the
development of guidelines and standards, increased capacity development in
generating and compiling food composition data, a food composition database
management system, improvements in laboratory quality assurance, and development
of several food composition databases and tables. Recently, INFOODS has led
efforts to define and document food biodiversity. As new foods and food
components come into prominence, and as analytical methods evolve, the activities
of INFOODS will continue to advance the quality and quantity of food composition
data globally into the future.
PMID- 26433280
TI - FAO/INFOODS e-Learning Course on Food Composition Data.
AB - The FAO/INFOODS e-Learning Course on Food Composition Data was developed to close
existing knowledge gaps on food composition of professionals working with those
data. It covers the important aspects of food composition, is based on
instructional design, is highly interactive and comprises 14 lessons of
approximate 10h duration. It was developed primarily for usage in universities,
but also suits self-paced learning and blended learning programmes. It is
available at: http://www.fao.org/infoods/infoods/training/en/ free-of-charge in
English, as on-line version or CD-ROM. Feedback from users was very positive and
universities start to incorporate it into their curricula. The translation into
other languages and the implementation of a certification and assessment
programme are envisaged. e-Learning is cost-effective and reaches a wide
audience. The course is expected to contribute to the improved data quality,
usage, generation, publication and appreciation of food composition data.
PMID- 26433281
TI - Comparison of methods for iodine analysis in foods.
AB - Spectrophotometric and ICP-MS methodology for iodine determination was compared.
Samples were alkali dry-ashed, dissolved in water, and iodine assayed by
spectrophotometry and by ICP-MS. Iodine content in the studied foods ranged from
3 to 1304MUg/100g. There was no significant difference (p>0.05) between iodine
values determined spectrophotometrically using an external calibration curve and
values determined using a standard addition. Foods containing low iodine
concentrations (4-25MUg/100g) also showed no significant difference (p>0.05)
between iodine concentrations determined spectrophotometrically and
concentrations determined by ICP-MS. For food items with more than 25MUg/100g,
the spectrophotometric methods yielded markedly higher (p<0.05) concentrations
than the standard ICP-MS method (relative positive bias 25-122%), especially in
foods with high sodium and/or iron contents. A catalytic effect of sodium and
iron on the Sandell and Kolthoff reaction, leading to false high values in the
spectrophotometric determination of iodine was demonstrated. ICP-MS is
recommended for iodine determination in foods.
PMID- 26433282
TI - Cholesterol determination in foods: Comparison between high performance and ultra
high performance liquid chromatography.
AB - Analytical methods for cholesterol evaluation in foods are crucial since this
compound was closely related with cardiovascular disease. In the present study,
two chromatographic methods were implemented and validated, in order to achieve
the ideal analytical method for the quantification of cholesterol in food
matrices. The developed methods were applied to different foodstuffs, sour cream,
egg, egg yolk and chicken nuggets. Both HPLC and UHPLC methods are rapid,
specific, sensitive, precise (RSD<2.5%) and accurate. The achieved LOD and LOQ
for UHPLC were 0.7 and 2.4MUg/mL, respectively, while for HPLC were 3 and
11MUg/mL. UHPLC method allowed reduction of the organic solvents consumption (8
times lower) and decreased analysis time in 4min, being more eco-friendly, than
conventional HPLC methods. Moreover, it will be very useful for the quality
control of cholesterol content in food matrices and can be easily adopted by
analytical laboratories.
PMID- 26433283
TI - A simplified HPLC method for determination of tryptophan in some cereals and
legumes.
AB - In the present study, a simple analytical method is proposed for determining
tryptophan, and method is validated on some cereal and legume samples. In the
method alkaline hydrolysis of proteins was used due to the destruction of
tryptophan structure during acid hydrolysis. Following alkaline hydrolysis (120
degrees C for 12h), hydrolysates are filtered through ashless filter paper and pH
values are adjusted with hydrochloric acid solution. Separation and detection of
tryptophan are performed on a reversed-phase column with fluorescence detection
within 10min by using a mobile phase of acetonitrile and acetate buffer of pH 6.3
(1:9, v/v). For determination of tryptophan content, the procedure described in
the study offers an alternative analysis method by enabling high speed analysis
and the use of simple extraction process to the other available methods.
PMID- 26433284
TI - Establishment and advances in the online Serbian food and recipe data base
harmonized with EuroFIRTM standards.
AB - Within the European Food Information Resource Network of Excellence (EuroFIR NoE;
FP6) and EuroFIR Nexus (FP7) project paucity in food composition databases (FCDB)
in the Central Eastern Europe/Balkan (CEE/B) region was identified. As a member
of EuroFIR NoE, the Centre of Research Excellence in Nutrition and Metabolism,
Serbia initiated creation of the 1st online Serbian FCDB employing EuroFIR
quality framework and CEN Food Data Standard requirements, supporting capacity
development and designing the web-based Food Composition Data Management (FCDM)
software for FCDB building. The 1st online version of Serbian FCDB was launched
in 2007, and then extended with food composition data from other Balkan countries
(Balkan Food Platform-Regional FCDB). All foods are indexed using LanguaL
Thesaurus and coded with EFSA FoodEx2 coding system. To date, upgraded Serbian
FCDB with 1046 foods and 129 traditional/common Serbian composite dishes is a
prerequisite for nutritional research in Serbia, CEE/B region and wider Europe.
PMID- 26433285
TI - Review of food composition data for edible insects.
AB - Edible insects are considered rich in protein and a variety of micronutrients,
and are therefore seen as potential contributors to food security. However, the
estimation of the insects' contribution to the nutrient intake is limited since
data are absent in food composition tables and databases. Therefore, FAO/INFOODS
collected and published analytical data from primary sources with sufficient
quality in the Food Composition Database for Biodiversity (BioFoodComp). Data
were compiled for 456 food entries on insects in different developmental stages.
A total of 5734 data points were entered, most on minerals and trace elements
(34.8%), proximates (24.5%), amino acids (15.3%) and (pro)vitamins (9.1%). Data
analysis of Tenebrio molitor confirms its nutritive quality that can help to
combat malnutrition. The collection of data will assist compilers to incorporate
more insects into tables and databases, and to further improve nutrient intake
estimations.
PMID- 26433286
TI - Assessment of the nutritional composition of quinoa (Chenopodium quinoa Willd.).
AB - Quinoa (Chenopodium quinoa Willd.) is an ancient crop which can play an important
role for worldwide food security. The current review aimed at evaluating existing
compositional data which were compiled according to international standards. A
limited number of data were found that met the dataset quality criteria. In
general, high variations in nutrient contents of quinoa were observed per 100g
edible portion on fresh weight basis, for example: protein (9.1-15.7g), total fat
(4.0-7.6g) and dietary fiber (8.8-14.1g). The variations of nutrient values among
different varieties and among different data sources were considerable. The
results show the nutritional potential of quinoa but they also demonstrate that
more high-quality analytical data of quinoa are needed, especially for minerals
and vitamins.
PMID- 26433287
TI - Protein content and amino acids profile of pseudocereals.
AB - Quinoa (Chenopodium quinoa), amaranth (Amaranthus caudatus) and buckwheat
(Fagopyrum esculentum) represent the main protein source in several diets,
although these pseudocereals are not currently present in the FCDB nutrient
profile information. The aim of this work is to characterise the AA profile of
these pseudocereals and compare them with rice. Total protein content revealed to
vary from 16.3g/100g (quinoa Salta) to 13.1g/100g (buckwheat) and lower values
were found in rice samples (6.7g/100g). For pseudocereals the most abundant
essential AA was leucine. Quinoa-Salta evidences the highest leucine content
(1013mg/100g) and the minor methionine content (199mg/100g). Buckwheat was the
cereal with the highest phenylalanine content (862mg/100g). Rice (Oryza sativa)
presents the lowest content for all AA. Results showed pseudocereals as the best
source of AA. EuroFIR guidelines where strictly followed and proved to be a
crucial tool to guarantee data interchangeability and comparability.
PMID- 26433288
TI - Aibika (Abelmoschus manihot L.): Genetic variation, morphology and relationships
to micronutrient composition.
AB - Aibika (Abelmoschus manihot L.) is believed to be a good source of
micronutrients. However, although many varieties of aibika are commonly consumed
in Papua New Guinea, their micronutrient content is unknown. Therefore, the
mineral (Ca, Fe, K, Mg, Mn, Na, Zn & Cu), folate composition and the genetic
variation of 23 aibika accessions from the collection at the National
Agricultural Research Institute were studied over a 3year period to provide data
for nutritional studies and to inform breeding programs. The data showed that
aibika is, potentially, a crop of high nutritional value with the potential to
boost the micronutrient status of local PNG communities. However, there were
substantial differences in the micronutrient concentrations of the accessions
from year to year and accessions that had the highest concentration of a
particular mineral in 1year did not have the high concentrations in other years.
Clusters determined using unweighted pair group method with arithmetic mean
analysis (UPGMA) of the micronutrient contents differed in each of the 3years.
Genetic analysis made using random amplification of polymorphic DNA and directed
amplification of mini satellite region DNA placed the accessions into five
groups. There was no correlation between these groups and leaf morphology, nor
were there correlations with the clusters determined from the UPGMA analyses.
There appears to be considerable interaction between genotype and environmental
factors determining micronutrient composition and environmental factors may play
a greater role than genotype in influencing micronutrient composition.
PMID- 26433289
TI - EuroFIR quality approach for managing food composition data; where are we in
2014?
AB - A EuroFIR quality management framework was developed to assure data quality of
food composition data, incorporating several recommendations developed or
improved during the EuroFIR projects. A flow chart of the compilation process
with standard operating procedures to assure critical steps was the starting
point. Recommendations for food description, component identification, value
documentation, recipe calculation, quality evaluation of values, guidelines to
assess analytical methods, document and data repositories and training
opportunities were harmonized as elements of the quality framework. European food
composition database organizations reached consensus on the EuroFIR quality
framework and started implementation. Peer reviews of the European compiler
organizations were organized to evaluate the quality framework, focusing on what
was achieved and on improvements needed. The reviews demonstrated that European
food database compilers have made good use of standards and guidelines produced
by EuroFIR, as well as a common understanding that a quality framework is
essential to assure food composition data quality.
PMID- 26433290
TI - Improving food composition data quality: Three new FAO/INFOODS guidelines on
conversions, data evaluation and food matching.
AB - Food composition data play a key role in many sectors and the availability of
quality data is critically important. Since 1984, the International Network of
Food Data Systems (INFOODS) has been working towards improving food composition
data quality and availability, including the development and updating of
standards, guidelines and tools for food composition. FAO/INFOODS has recently
published three comprehensive guidelines to improve and harmonise the compilation
of data: (1) Guidelines for Food Matching, (2) Guidelines for Checking Food
Composition Data prior to Publication of a User Table/Database, and (3)
Guidelines for Converting Units, Denominators and Expressions. This article
describes their content and development processes. Their adoption, along with
additional ones planned for the future by FAO/INFOODS, should further improve the
quality of published food composition data, which in turn can lead to more
accurate nutrient intake estimates and more precise food labels, as well as
better-targeted programs and policies.
PMID- 26433291
TI - EuroFIR guidelines for assessment of methods of analysis: GAMA.
AB - Analytical methodology is a key factor in food composition databases and specific
criteria, at the component level, is needed for comparison of analytical data
from different sources. The aim of this work is to describe how EuroFIR
guidelines for assessment of methods of analysis are created and made available
to users. Comprehensive information for macronutrients, vitamins, minerals and
trace elements addressing all aspects of analytical procedures was obtained from
international standards, and scientific literature. Documentation was compiled in
a confluence wiki format provided for each component: background information,
description of reference methods of analysis and critical steps, available
reference materials, proficiency testing schemes, other analytical methods and
relevant references. The information for each nutrient was collated, edited and
presented with hypertext links to additional pages where more detailed
information can be accessed using full text searches. The wiki format is a useful
tool for preparing information and disseminating to users.
PMID- 26433292
TI - Implementing the EuroFIR Document and Data Repositories as accessible resources
of food composition information.
AB - The EuroFIR Document and Data Repositories are being developed as accessible
collections of source documents, including grey literature, and the food
composition data reported in them. These Repositories will contain source
information available to food composition database compilers when selecting their
nutritional data. The Document Repository was implemented as searchable
bibliographic records in the Europe PubMed Central database, which links to the
documents online. The Data Repository will contain original data from source
documents in the Document Repository. Testing confirmed the FoodCASE food
database management system as a suitable tool for the input, documentation and
quality assessment of Data Repository information. Data management requirements
for the input and documentation of reported analytical results were established,
including record identification and method documentation specifications. Document
access and data preparation using the Repositories will provide information
resources for compilers, eliminating duplicated work and supporting unambiguous
referencing of data contributing to their compiled data.
PMID- 26433293
TI - Total and haem iron content lean meat cuts and the contribution to the diet.
AB - This study provides data on the total and haem iron contents in raw lean beef,
chicken, lamb and pork meat samples. Total iron, expressed as mg/100g edible
portion on fresh weight basis in raw lean beef (A-age), lamb, pork and chicken
average 1.58, 1.64, 0.81 and 0.78, respectively. The haem iron content in beef (A
age), lamb, pork and chicken are 77%, 81%, 88% and 74% respectively of total
iron. This has important dietary implications in calculating haem iron fractions
of meat as this is higher than the common value used in the Monsen equation.
PMID- 26433294
TI - Inulin content of fortified food products in Thailand.
AB - This study examined inulin content in 266 samples. They were 126 dried, 105
liquid and 27 semi-solid of twelve commercial inulin fortified food products and
8 samples of natural dried sunchoke. For dried food products, inulin content
ranged from 3.0 +/-0.8g/100g fresh weight (FW) in milk powder to 83.7+/-
17.8g/100g FW in inulin powder. The levels in a descending order are the powder
of inulin, weight control diet, coffee mixed, instant beverage, supplemented food
products for pregnant and milk. For liquid fortified foods, inulin at the level
of 0.3+/- 0.1g/100mL FW was found in UHT milk, and up to 13.5+/- 4.1g/100mL FW in
weight control diet beverage. The level of 2.0-2.3g/100g FW of inulin was found
in beverage with different flavours, soybean milk and fruit juice. For semi-solid
food, cream yoghurt, inulin at 3.9+/- 1.1g/100g FW was found. A serving of most
products contributes inulin at 11-33% of the recommended daily intake of dietary
fibre.
PMID- 26433295
TI - Australian seafood compositional profiles: A pilot study. Vitamin D and mercury
content.
AB - Given the scarcity of comprehensive nutritional data for Australia's >400
commercially produced seafood species a pilot study was undertaken to collect and
analyse 22 species of wild and aquaculture seafood in order to develop a model
for future comprehensive surveys. The species analysed were: Atlantic salmon,
Australian sardine, prawn (six species), barramundi, abalone (three species),
blue sprat, burrowing blackfish, gummy shark, oyster (four species), ocean trout
and yellowtail kingfish. The analyses undertaken in this pilot study were:
moisture, protein, total fat, cholesterol, fatty acids, vitamin C, vitamins A and
D, and 21 mineral elements (including total mercury and methyl mercury). The data
reported here are for vitamin D and mercury only. Comprehensive data have already
been published elsewhere. Issues identified that should be addressed prior to
undertaking a more extensive and representative study of the remaining major
edible commercial Australian seafood species include: choice of samples and
nutrients for analysis, facilities for sample handling and storage, data
management and scrutiny, and laboratory quality control.
PMID- 26433296
TI - Report on the development of the FAO/INFOODS user database for fish and shellfish
(uFiSh) - Challenges and possible solutions.
AB - Reliable food composition data are required for virtually all nutrition-related
programs and policies. In many food composition tables, fish are included to a
limited extent. Therefore, FAO/INFOODS decided to compile and publish a user
databases for fish and shellfish (uFiSh), considering the following main
objectives: to develop a global database for fish, crustaceans and molluscs with
raw, cooked and processed foods; to base the database preferable on analytical
data; to include major as well as minor species consumed; and to capture intra
species variation due to habitat, edible part, season or region. The development
of the uFiSh is based on FAO/INFOODS international standards and guidelines. The
paper describes challenges and possible solution of data compilation specific to
fish and shellfish, as well as the uFiSh in terms of its structure, including
coverage of nutrients, documentation and format of publication. The first edition
is intended to be published in 2015.
PMID- 26433298
TI - Impact of dietary fiber energy on the calculation of food total energy value in
the Brazilian Food Composition Database.
AB - Dietary fiber (DF) contributes to the energy value of foods and including it in
the calculation of total food energy has been recommended for food composition
databases. The present study aimed to investigate the impact of including energy
provided by the DF fermentation in the calculation of food energy. Total energy
values of 1753 foods from the Brazilian Food Composition Database were calculated
with or without the inclusion of DF energy. The energy values were compared,
through the use of percentage difference (D%), in individual foods and in daily
menus. Appreciable energy D% (?10) was observed in 321 foods, mainly in the group
of vegetables, legumes and fruits. However, in the Brazilian typical menus
containing foods from all groups, only D%<3 was observed. In mixed diets, the DF
energy may cause slight variations in total energy; on the other hand, there is
appreciable energy D% for certain foods, when individually considered.
PMID- 26433297
TI - ePlantLIBRA: A composition and biological activity database for bioactive
compounds in plant food supplements.
AB - The newly developed ePlantLIBRA database is a comprehensive and searchable
database, with up-to-date coherent and validated scientific information on plant
food supplement (PFS) bioactive compounds, with putative health benefits as well
as adverse effects, and contaminants and residues. It is the only web-based
database available compiling peer reviewed publications and case studies on PFS.
A user-friendly, efficient and flexible interface has been developed for
searching, extracting, and exporting the data, including links to the original
references. Data from over 570 publications have been quality evaluated and
entered covering 70 PFS or their botanical ingredients.
PMID- 26433299
TI - Compilation of a standardised international folate database for EPIC.
AB - This paper describes the methodology applied for compiling an "international end
user" folate database. This work benefits from the unique dataset offered by the
European Prospective Investigation into Cancer and Nutrition (EPIC) (N=520,000
subjects in 23 centres). Compilation was done in four steps: (1) identify folate
free foods then find folate values for (2) folate-rich foods common across EPIC
countries, (3) the remaining "common" foods, and (4) "country-specific" foods.
Compiled folate values were concurrently standardised in terms of unit, mode of
expression and chemical analysis, using information in national food composition
tables (FCT). 43-70% total folate values were documented as measured by
microbiological assay. Foods reported in EPIC were either matched directly to FCT
foods, treated as recipes or weighted averages. This work has produced the first
standardised folate dataset in Europe, which was used to calculate folate intakes
in EPIC; a prerequisite to study the relation between folate intake and diseases.
PMID- 26433300
TI - Validation of a sampling plan to generate food composition data.
AB - A methodology to develop systematic plans for food sampling was proposed. Long
life whole and skimmed milk, and sunflower oil were selected to validate the
methodology in Argentina. Fatty acid profile in all foods, proximal composition,
and calcium's content in milk were determined with AOAC methods. The number of
samples (n) was calculated applying Cochran's formula with variation coefficients
?12% and an estimate error (r) maximum permissible ?5% for calcium content in
milks and unsaturated fatty acids in oil. n were 9, 11 and 21 for long life whole
and skimmed milk, and sunflower oil respectively. Sample units were randomly
collected from production sites and sent to labs. Calculated r with experimental
data was ?10%, indicating high accuracy in the determination of analyte content
of greater variability and reliability of the proposed sampling plan. The
methodology is an adequate and useful tool to develop sampling plans for food
composition analysis.
PMID- 26433301
TI - Voluntary fortification with folic acid in Spain: An updated food composition
database.
AB - Folic acid (FA) is a key vitamin in the prevention of many diseases including
neural tube defects. In Spain, only voluntary FA food fortification is allowed
and there is a lack of compositional data to assess the contribution of these
products to population's dietary folate intakes. Since 2007, our group has been
compiling and updating a FA fortified food composition database. FA levels were
obtained from retailers in Madrid and information provided by manufacturers. FA
was also quantified by an affinity chromatography-HPLC method. In the present
study we recorded 375 products. Our results show a high variability in the
declared FA levels amongst different products, and food groups, which is also
dependant on the commercial brand. FA overages are commonly added by
manufacturers to some fortified products. FA content label claims are missing in
64% of products. This database is a useful tool to manage FA fortified foods data
but it is necessary to continuously update it for the sound evaluation and
monitoring of population's FA dietary intakes.
PMID- 26433302
TI - Nutrient and phytochemical composition of two varieties of Monkey kola (Cola
parchycarpa and Cola lepidota): An underutilised fruit.
AB - The nutrient and phytochemical composition of two varieties of Monkey kola: Cola
parchycarpa and Cola lepidota were determined. The pulps were extracted, grated
and dried using solar dryer. Dried pulps were milled into flour with attrition
milling machine (0.5mm sieve size). The nutrient compositions were determined
using standard AOAC methods. Gravimetric and spectrophotometric methods were used
for phytochemical determinations. There were significant (p<0.05) differences in
the proximate and some mineral and vitamin composition of the two varieties. Most
abundant minerals were calcium (195-199mg for C. parchycarpa), potassium (204
209mg/100g for C. lepidota) and beta-carotene (2755-5028MUg/100g for C.
parchycarpa). Calcium:phosphorus and sodium:potassium ratios were adequate (>1.0
and ?0.06, respectively). Monkey kola had substantial amounts of iron, zinc, and
copper; the B-vitamins and vitamin C. The phytochemical contents were quiet high,
the most abundant being flavonoids (415-494mg/100g). Monkey kola is a fruit that
should be fully exploited for its potential health benefits.
PMID- 26433303
TI - Effect of animal age and trimming practices on the physical composition of
Bonsmara beef.
AB - Increased economic incentive for producing young and leaner carcasses, as well as
demand for lean meat from progressively health conscious consumers, are
considered drivers for change in carcass composition over time. Furthermore, many
retailers trim visible fat from meat to various degrees and consumers
increasingly remove visible fat from meat prior to, or after, cooking. The
objective of this study was to determine the composition of South African
Bonsmara beef from four age groups from different production systems, as well as
to extrapolate the effect of fat trimming on physical composition. Fat content of
marketable beef has decreased notably since the 1930s, and beef from the South
African Bonsmara breed contains less than 10g lipid per 100g after trimming of
subcutaneous fat, irrespective of age. Removal of all visible fat reduces the
lipid content to less than 5g per 100g, comparing favourably with other lean
animal products.
PMID- 26433304
TI - A scope classification of data quality requirements for food composition data.
AB - Data quality is an important issue when managing food composition data since the
usage of the data can have a significant influence on policy making and further
research. Although several frameworks for data quality have been proposed,
general tools and measures are still lacking. As a first step in this direction,
we investigated data quality requirements for an information system to manage
food composition data, called FoodCASE. The objective of our investigation was to
find out if different requirements have different impacts on the intrinsic data
quality that must be regarded during data quality assessment and how these
impacts can be described. We refer to the resulting classification with its
categories as the scope classification of data quality requirements. As proof of
feasibility, the scope classification has been implemented in the FoodCASE
system.
PMID- 26433305
TI - Improving nutrition surveillance and public health research in Central and
Eastern Europe/Balkan Countries using the Balkan Food Platform and dietary tools.
AB - The objective of this paper is to share experience and provide updated
information on Capacity Development in the Central and Eastern Europe/Balkan
Countries (CEE/BC) region relevant to public health nutrition, particularly in
creation of food composition databases (FCDBs), applying dietary intake
assessment and monitoring tools, and harmonizing methodology for nutrition
surveillance. Balkan Food Platform was established by a Memorandum of
Understanding among EuroFIR AISBL, Institute for Medical Research, Belgrade,
Capacity Development Network in Nutrition in CEE - CAPNUTRA and institutions from
nine countries in the region. Inventory on FCDB status identified lack of
harmonized and standardized research tools. To strengthen harmonization in CEE/BC
in line with European research trends, the Network members collaborated in
development of a Regional FCDB, using web-based food composition data base
management software following EuroFIR standards. Comprehensive nutrition
assessment and planning tool - DIET ASSESS & PLAN could enable synchronization of
nutrition surveillance across countries.
PMID- 26433306
TI - Nutrients and bioactive compounds in popular and indigenous durian (Durio
zibethinus murr.).
AB - This study identified nutrients, fatty acids, bioactive compounds and antioxidant
activities of two popular varieties (Mon-thong, Cha-ni) and two indigenous
varieties (Kra-dum and Kob-ta-kam) of durian. Each of variety was collected from
3 gardens in Nonthaburi province, Thailand. At optimal ripeness, the edible part
was separated, homogenised or freeze dried, as fresh or dry samples for further
analysis using standard methods. All durian varieties contained a considerable
amount of dietary fibre (7.5-9.1g/100g dry matter, DM) and high amounts of
carbohydrate and sugar (62.9-70.7g and 47.9-56.4g/100g DM respectively). Cha-ni,
Kra-dum and Kob-ta-kam varieties had monounsaturated (MUFA) (6.1-7.8g/100g
DM)>saturated (SFA) (4.2-5.7g/100g DM)>polyunsaturated fatty acid (PUFA) (0.8
1.5g/100g DM), whereas the Mon-thong variety had SFA>MUFA>PUFA (5.1, 4.0,
1.1g/100g DM, respectively). The Kob-ta-kam variety showed greater potential for
health benefits in terms of carotenoids and beta-carotene (2248MUg and
1202MUg/100g DM respectively). Phenolic compounds and antioxidant capacity were
not significantly different among each variety, though the Cha-ni variety had the
lowest. This study provides data on nutrients, bioactive compounds and
antioxidant activities of indigenous and popular durian varieties that could be
used for consumer education as well as for incorporation into the food
composition databases.
PMID- 26433307
TI - Nutritional and phytochemical composition of Annona cherimola Mill. fruits and by
products: Potential health benefits.
AB - Annona cherimola Mill., commonly known as cherimoya, is a tropical fruit well
known due to its tasty flavour. In the present study the antioxidant activity of
pulp, peel and seeds of four cultivars from A. cherimola Mill. from Madeira
Island (Madeira, Funchal, Perry Vidal and Mateus II) was analysed. Moreover,
nutritional composition (proximates and vitamins) and bioactive compounds content
were determined. The peel of Madeira cultivar showed the highest antioxidant
capacity, with an EC50 of 0.97mg/mL, and total flavonoids (44.7 epicatechin
equivalents/100g). The most abundant carotenoid was lutein, with values ranging
from 129 to 232MUg/100g. The highest l-ascorbic acid content (4.41mg/100g) was
found in the peel of Perry Vidal cultivar. These results highlight A. cherimola
Mill. antioxidant properties, especially in its by-products and encourage their
application in cosmetic, pharmaceutical and food processing industries, as added
value natural extracts.
PMID- 26433308
TI - The use of food composition data in the Choices International Programme.
AB - Food composition data have extensively been used in the Choices International
Programme: they formed the basis of both criteria development and nutrient intake
modeling. Criteria were developed for key nutrients linked to non communicable
diseases by an independent scientific committee. The criteria can be used for the
logo assignment on food products, in order to stimulate producers to improve
their products and to stimulate consumers to purchase these products. Insights in
steps of development of the criteria for the Choices program illustrates the
importance of food composition data in this process. Modeling studies with the
criteria for the Dutch Choices program showed an improved nutrient intake profile
if consumers would choose products fulfilling the criteria of the Dutch logo as
part of their diets. The role and availability of food composition databases in
the development of the criteria and the modeling studies is discussed.
PMID- 26433309
TI - [Testosterone deficiency, metabolic syndrome and diabetes mellitus].
AB - Testosterone deficiency in adult age is associated with a decrease in libido,
energy, hematocrit, muscle mass and bone mineral density, as well as with
depression. More recently, testosterone deficiency has also been associated with
various components of the metabolic syndrome, which in turn is associated with a
five-fold increase in the risk of cardiovascular disease. Low testosterone levels
are associated with increased insulin resistance, increase in fat mass, low HDL
cholesterol, higher triglyceride levels and hypertension. Testosterone
replacement therapy in patients with testosterone deficiency and type 2 diabetes
mellitus and/or metabolic syndrome has shown reductions in insulin resistance,
total cholesterol, LDL cholesterol and triglycerides and improvement in glycemic
control and anthropometric parameters.
PMID- 26433310
TI - [Post-thrombotic syndrome: A pending issue].
PMID- 26433311
TI - [Primary cutaneous amyloidosis of the external ear: A peculiar, unusual and
benign entity].
PMID- 26433313
TI - Next-Generation Sequencing for Infectious Disease Diagnosis and Management: A
Report of the Association for Molecular Pathology.
AB - Next-generation sequencing (NGS) technologies are increasingly being used for
diagnosis and monitoring of infectious diseases. Herein, we review the
application of NGS in clinical microbiology, focusing on genotypic resistance
testing, direct detection of unknown disease-associated pathogens in clinical
specimens, investigation of microbial population diversity in the human host, and
strain typing. We have organized the review into three main sections: i)
applications in clinical virology, ii) applications in clinical bacteriology,
mycobacteriology, and mycology, and iii) validation, quality control, and
maintenance of proficiency. Although NGS holds enormous promise for clinical
infectious disease testing, many challenges remain, including automation,
standardizing technical protocols and bioinformatics pipelines, improving
reference databases, establishing proficiency testing and quality control
measures, and reducing cost and turnaround time, all of which would be necessary
for widespread adoption of NGS in clinical microbiology laboratories.
PMID- 26433312
TI - Aberrant Levels of miRNAs in Bone Marrow Microenvironment and Peripheral Blood of
Myeloma Patients and Disease Progression.
AB - The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to
play a role in the biology of disease. In this study, we found that the
extracellular BM microenvironment in MM contains a unique miRNA signature
detectable by miRNA microarray and quantitative real-time PCR, which is partially
represented in the peripheral blood. Eleven miRNAs were significantly decreased
in both BM and serum of MM patients in comparison with controls. Evaluation of
these miRNAs in plasma of a separate cohort of MM patients and controls confirmed
significantly aberrant levels of let-7a, let-7b, let-7i, miR-15b, miR-16, and miR
20a in both serum and plasma. We then studied the myeloma precursor diseases and
found that a subset of the MM miRNAs exhibited aberrant expression in monoclonal
gammopathy of undetermined significance and smoldering myeloma. miRNA analysis of
enriched CD138(+) plasma cells from MM and monoclonal gammopathy of undetermined
significance found that most of the validated MM BM signature miRNAs were
significantly decreased in MM plasma cells. Gene expression profiling indicated
that multiple targets of the decreased miRNAs found increased expression in MM
plasma cells, including ATF2, HRAS, HDAC4, TGFB1, TGFBR1, and mitogen-activated
protein kinases. The findings suggest that these miRNAs are detectable in
aberrant levels in the peripheral blood of patients with plasma cell
proliferation and may play a role in aberrant plasma cell proliferation and
disease progression.
PMID- 26433315
TI - [Early epithelial lesions in prophylactic annexectomies in patients at high risk
of ovarian cancer: Report of a series of 93 cases].
AB - OBJECTIVE: Tubal lesions detected in specimen of risk reducing salpingo
oophorectomy (RRSO) for mutation BRCA1/2 seems to play a role in ovarian
carcinogenesis. The main objective of this study is to evaluate the prevalence of
occult neoplasia, of Serous Tubal Intraepithelial Carcinoma (STIC), and signature
P53 in a cohort of patients who underwent a risk reducing salpingo oophorectomy.
METHODS: From January 2010 to January 2014 unicentric, retrospective study on a
consecutive cases cohort of RRSO for patients with a high risk of ovarian
neoplasia (mutation BRCA 1/2 or family history). Pathological specimen should be
analysed according to the SEE-FIM protocol. RESULTS: Ninety-three RRSO were
recorded. Among them, 44% of the patients had the germ line mutation BRCA1, 30.1%
BRAC2 and 18.2% had no identified mutation. In all, 33.3% of the RRSO reveal a
signature P53, in the fimbria for 93.9%, 7.9% of them were bilateral. 1,10/00
(n=1) of the patients presented a unilateral STIC. We obtained 4.3% of occult
neplasia: 3 ovarian high-grade serous carcinomas and 1 tubal high-grade serous
carcinoma. Only the tubal carcinoma coexists with STIC. CONCLUSION: 5,4% of the
patients who underwent RRSO had a diagnostic of occult neoplasia. One percent of
the patients had an isolated STIC. These results agree with recent data of the
literature. Extensive examination of the Fallopian tube opens up a new way to
understand ovarian carcinogenesis.
PMID- 26433316
TI - [Social inequalities in maternal health].
AB - Although medical literature on social inequalities in perinatal health is
qualitatively heterogeneous, it is quantitatively important and reveals the
existence of a social gradient in terms of perinatal risk. However, published
data regarding maternal health, if also qualitatively heterogeneous, are
relatively less numerous. Nevertheless, it appears that social inequalities also
exist concerning severe maternal morbidity as well as maternal mortality.
Analyses are still insufficient to understand the mechanisms involved and explain
how the various dimensions of the women social condition interact with maternal
health indicators. Inadequate prenatal care and suboptimal obstetric care may be
intermediary factors, as they are related to both social status and maternal
outcomes, in terms of maternal morbidity, its worsening or progression, and
maternal mortality.
PMID- 26433317
TI - Medial thighplasty: Current concepts and practices.
AB - Medial thighplasty, also known as medial thigh lift, is a procedure that has been
carried out for five decades. The original "Lewis" technique has undergone many
changes, and thereby been rendered widely available to plastic surgeons. Given
the increasingly high number of surgical reconstructions after massive weight
loss, this technique is now an integral part of a surgeon's therapeutic arsenal
as he strives to meet the evolving demands of patients. The objective of this
article, which is based on a comprehensive review of the literature, is to
summarize current knowledge on medial thighplasty and thereby allow plastic
surgeons to adopt the operating technique best suited to the deformations
presented by their patients and to the overall context. The different techniques,
outcomes and complications are successively discussed.
PMID- 26433319
TI - Is it time for treat to target in psoriatic arthritis?
PMID- 26433318
TI - Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a
UK multicentre, open-label, randomised controlled trial.
AB - BACKGROUND: Early intervention and tight control of inflammation optimise
outcomes in rheumatoid arthritis but these approaches have not yet been studied
in psoriatic arthritis. We aimed to assess the effect of tight control on early
psoriatic arthritis using a treat-to-target approach. METHODS: For this open
label multicentre randomised controlled trial, adult patients (aged >=18 years)
with early psoriatic arthritis (<24 months symptom duration), who had not
previously received treatment with any disease-modifying anti-rheumatic drugs,
were enrolled from eight secondary care rheumatology centres in the UK. Enrolled
patients were randomly assigned in a 1:1 ratio to receive either tight control
(with review every 4 weeks and with escalation of treatment if minimal disease
activity criteria not met) or standard care (standard therapy according to the
treating clinician, with review every 12 weeks) for 48 weeks. Randomisation was
done by minimisation incorporating a random element, to ensure treatment groups
were balanced for randomising centre and pattern of arthritis (oligoarticular vs
polyarticular). The randomisation procedure was done through a central 24-h
automated telephone system based at the Leeds Institute of Clinical Trials
Research (Leeds, UK). This was an open-label study in which patients and
clinicians were aware of treatment group assignment. Clinical outcomes were
recorded by a masked assessor every 12 weeks. The primary outcome was the
proportion of patients achieving an American College of Rheumatology (ACR) 20%
(ACR20) response at 48 weeks, analysed by intention to treat with multiple
imputation for missing ACR components. Cost-effectiveness was also assessed. This
trial is registered with ClinicalTrials.gov, number NCT01106079, and the ISCRCTN
registry, number ISCRCTN30147736. FINDINGS: Between May 28, 2008, and March 21,
2012, 206 eligible patients were enrolled and randomly assigned to receive tight
control (n=101) or standard care (n=105). In the intention-to-treat patient
population, the odds of achieving an ACR20 response at 48 weeks were higher in
the tight control group than in the standard care group (odds ratio 1.91, 95% CI
1.03-3.55; p=0.0392). Serious adverse events were reported by 20 (10%) patients
(25 events in 14 [14%] patients in the tight control group and eight events in
six [6%] patients in the standard care group) during the course of the study. No
unexpected serious adverse events or deaths occurred. INTERPRETATION: Tight
control of psoriatic arthritis disease activity through a treat-to-target
approach significantly improves joint outcomes for newly diagnosed patients, with
no unexpected serious adverse events reported. FUNDING: Arthritis Research UK and
Pfizer.
PMID- 26433320
TI - Editorial overview: Protein design and evolution-new protein architectures,
evolutionary fine-tuning and analysis.
PMID- 26433321
TI - The International Conference on Radioecology and Environmental Radioactivity,
2014, (ICRER-2014).
PMID- 26433322
TI - Nipple discharge: The role of imaging.
AB - Nipple discharge is a common symptom in breast medicine. It is usually benign in
origin (papillomas and galactophore duct ectasia) although it is essential not to
miss the risk of an underlying malignant lesion (5%) mostly due to in situ
carcinomas. Clinical examination is essential in the management, distinguishing
benign "physiological" discharge from discharge suspected of being "pathological"
in which further investigations with mammography and ultrasound are required.
When the conventional imaging assessment for pathological nipple discharge is
normal, breast MRI is gradually replacing galactography although this is still an
emerging and invalidated indication. In this context and if the whole imaging
assessment is normal, surgery is no longer the only solution for patients, who
can now be offered regular monitoring.
PMID- 26433323
TI - Image-guided percutaneous internal fixation of sacral fracture.
AB - Percutaneous iliosacral screw placement is a technically challenging procedure
with a significant complication profile for misplaced screws. The use of
stereotactic image guidance has been shown to provide superior accuracy in the
placement of spinal instrumentation. Here, the authors describe a novel
application of O-arm technology (Medtronic Sofamor Danek, Memphis, TN, USA) to
help safely place iliosacral screws for the treatment of a traumatic sacral
fracture.
PMID- 26433324
TI - The vagaries of proper imaging in diagnosing single-system ectopic ureter in
children with continuous incontinence and outcomes of simple nephrectomy.
AB - PURPOSE: To investigate the proper diagnostic modalities and failure cases of
treatment in patients with single-system ectopic ureter (SSEU) who underwent
nephrectomy for incontinence. METHODS: SSEU combined with dysplastic kidney is a
rare cause of female incontinence. We retrospectively analyzed 45 pediatric SSEU
patients that underwent simple nephrectomy at our institution during 1996-2013
for incontinence. We reviewed imaging studies to detect dysplastic kidney and
ectopic ureter insertion, postoperative results, and urodynamic findings for
remaining incontinence after nephrectomy. RESULTS: Median operative age was
59.3months. Both ultrasonography and magnetic resonance imaging (MRI) showed
50.0% dysplastic kidney detection rates respectively. Dimercaptosuccinic acid
(DMSA) scanning and computerized tomography (CT) showed equal detection rates of
95.5%. Ectopic ureter insertion sites were determined by ultrasonography, CT, and
MRI in 17.5%, 13.6%, and 33.3% of patients, respectively. Renal vascular
structures were identified in 3/22 patients (13.6%) with CT. Post-nephrectomy,
incontinence disappeared in 41 patients (91.1%), but remained in 4 patients
(8.9%); urodynamics suggested bladder neck incompetence in these patients.
CONCLUSIONS: DMSA is a highly sensitive diagnostic modality for detecting
dysplastic kidney in SSEU patients with more than 95% detection rates. Once
detected by DMSA, additional CT or MRI studies do not provide further information
about ectopic ureter insertion or renal vascular structure. Although nephrectomy
is successful in nearly 90% of SSEU patients with dysplastic kidneys,
postoperative incontinence occasionally remains and requires additional
treatment.
PMID- 26433325
TI - The neuroendocrine response to stress under the effect of drugs: Negative synergy
between amphetamine and stressors.
AB - There have been numerous studies into the interaction between stress and
addictive drugs, yet few have specifically addressed how the organism responds to
stress when under the influence of psychostimulants. Thus, we studied the effects
of different acute stressors (immobilization, interleukin-1beta and forced
swimming) in young adult male rats simultaneously exposed to amphetamine (AMPH, 4
mg/kg SC), evaluating classic biological markers. AMPH administration itself
augmented the plasma hypothalamic-pituitary-adrenal (HPA) hormones,
adrenocorticotropin (ACTH) and corticosterone, without affecting plasma glucose
levels. By contrast, this drug dampened the peripheral HPA axis, as well as the
response of glucose to the three stressors. We also found that AMPH
administration completely blocked the forced swim-induced expression of the
corticotropin-releasing hormone (hnCRH) and it partially reduced c-fos expression
in the paraventricular nucleus of the hypothalamus (PVN). Indeed, this negative
synergy in the forced swim test could even be observed with a lower dose of AMPH
(1mg/kg, SC), a dose that is usually received in self-administration experiments.
In conclusion, when rats that receive AMPH are subjected to stress, a negative
synergy occurs that dampens the prototypic peripheral physiological response to
stress and activation of the PVN.
PMID- 26433326
TI - An ultra-sensitive monoclonal antibody-based enzyme-linked immunosobent assay for
dibutyl phthalate in human urinary.
AB - Dibutyl phthalate (DBP) has been extensively used as a plasticizer in many daily
products, which is highly toxic to human, notably affecting the reproductive and
developmental function. As the previous method is expensive, time-consuming, low
sensitivity and just focused on the environment. Present study was aimed to
establish an ultra-sensitive and simple method based on good quality monoclonal
antibody, applying to evaluate excretion level of DBP in urine samples of Chinese
population directly. A monoclonal antibody was generated and characterized after
fusion of myeloma cells with spleen cells isolated from BALB/c mouse. The mouse
was previously immunized using a specially designed amino derivative of DBP
conjugated with bovine serum albumin (BSA) as immunogen. Cross-reactivity values
of the monoclonal antibody against DBP, di-isobutyl phthalate (DIBP) were
observed 100% and 1.25%, while for dimethyl phthalate (DMP), butyl benzyl
phthalate (BBP) and didecyl phthalate (DDP) the values were <0.06%. The standard
curve was constructed at 0-50 ng mL(-1) and good linearity (R(2)=0.994) was
achieved. The observed IC50 (7.34 ng mL(-1)) and LOD (0.06 ng mL(-1)) values was
improved 1000-fold to polyclonal antibody and 5-fold to other monoclonal
antibodies. A total 1246 urine samples were analyzed and the detection frequency
of DBP was observed 72.87% by ic-ELISA. The 95th percentile and mean
concentration of DBP were 12.07 and 3.00 ng mL(-1). Acceptable recovery rates of
DBP were 97.8-114.3% and coefficients variation 5.93-11.09%. The concentrations
of DBP in females were found significantly higher (p<0.05) than males. Similarly,
the DBP in middle aged and low educated individuals was found higher (p<0.001)
than the others. Considering the adverse health effects, DBP internal exposure in
the Chinese population should be reduced. The ic-ELISA method has been proved as
a cost effective, specific, and highly sensitive screening tool to detect DBP in
urinary samples.
PMID- 26433327
TI - Sources apportionment of PM2.5 in a background site in the North China Plain.
AB - To better understand the sources and potential source regions of PM2.5, a field
study was conducted from January 2011 to November 2011 at a background site, the
Yellow River Delta National Nature Reserve (YRDNNR) in the North China Plain.
Positive matrix factorisation (PMF) analysis and a potential source contribution
function (PSCF) model were used to assess the data, which showed that YRDNNR
experienced serious air pollution. Concentrations of PM2.5 at YRDNNR were 71.2,
92.7, 97.1 and 62.5 MUg m(-3) in spring, summer, autumn and winter, respectively,
with 66.0% of the daily samples exhibiting higher concentrations of PM2.5 than
the national air quality standard. PM2.5 mass closure showed remarkable seasonal
variations. Sulphate, nitrate and ammonium were the dominant fractions of PM2.5
in summer (58.0%), whereas PM2.5 was characterized by a high load of organic
aerosols (40.2%) in winter. PMF analysis indicated that secondary sulphate and
nitrate (54.3%), biomass burning (15.8%), industry (10.7%), crustal matter
(8.3%), vehicles (5.2%) and copper smelting (4.9%) were important sources of
PM2.5 at YRDNNR on an annual average. The source of secondary sulphate and
nitrate was probably industrial coal combustion. PSCF analysis indicated a
significant regional impact on PM2.5 at YRDNNR all year round. Local emission may
be non-negligible at YRDNNR in summer. The results of the present study provide a
scientific basis for the development of PM2.5 control strategies on a regional
scale.
PMID- 26433328
TI - Monitoring changes in the structure and properties of humic substances following
ozonation using UV-Vis, FTIR and (1)H NMR techniques.
AB - The main objective of this work is to conduct a comprehensive structural
characterization of humic substances using the following experimental techniques:
FTIR, 1H NMR and several UV-Vis parameters (Specific UV Absorbance at 254 nm or
SUVA254, SUVA280, A400, the absorbance ratios A210/254, A250/365, A254/203,
A254/436, A265/465, A270/400, A280/350, A465/665, the Absorbance Slope Index
(ASI), the spectral slopes S275-295, S350-400 and the slope ratio SR). These UV
Vis parameters have also been correlated with key properties of humic substances
such as aromaticity, molecular weight (MW) and trihalomethane formation potential
(THMFP). An additional objective of this work is also to evaluate the usefulness
of these techniques to monitor structural changes in humic substances produced by
the ozonation treatment. Four humic substances were studied in this work: three
of them were provided by the International Humic Substances Society (Suwannee
River Fulvic Acid Standard: SRFA, Suwannee River Humic Acid Standard: SRHA and
Nordic Reservoir Fulvic Acid Reference: NLFA) and the other one was a terrestrial
humic acid widely used as a surrogate for aquatic humic substances in various
studies (Aldrich Humic Acid: AHA). The UV-Vis parameters showing the best
correlations with aromaticity in this study were SUVA254, SUVA280, A280/A350
ratio and A250/A364 ratio. The best correlations with molecular weight were for
SUVA254, SUVA280 and A280/A350 ratio. Finally, in the case of the THMFP it was
STHMFP-per mol HS the parameter showing good correlations with most of the UV-Vis
parameters studied (especially with A280/A350 ratio, A265/A465 ratio and
A270/A400 ratio) whereas STHMFP-per mg C showed poor correlations in most cases.
On the whole, the UV-Vis parameter showing the best results was A280/A350 ratio
as it showed excellent correlations for the three properties studied
(aromaticity, MW and THMFP). A decrease in aromaticity following ozonation of
humic substances can be readily monitored by 1H NMR and FTIR; the latter
technique also allows to monitor an increase in carboxylic acidity with ozone
dosage. This organic matter originated following ozonation (more aliphatic in
character and more polar) is expected to be recalcitrant to further oxidation.
The terrestrial humic acid (AHA) showed some structural differences with the
aquatic humic substances and its behavior upon ozonation also differed in some
extent from that shown by them.
PMID- 26433329
TI - Application of IEUBK model in lead risk assessment of children aged 61-84 months
old in central China.
AB - Few studies have focused on the accuracy of using the Integrated Exposure Uptake
Biokinetic (IEUBK) model in Chinese children with site- and age-specific exposure
data. This study aimed to validate the accuracy and sensitivity of the IEUBK
model in lead risk assessment of Chinese children aged 61-84 months old. A total
of 760 children were enrolled from two respective counties in Central China by
using random cluster sampling method. Blood lead levels (BLLs) of all subjects
were determined using graphite furnace atomic absorption spectrometry, as well as
that in the environmental media, such as air, drinking water, soil, dust and
food. Age- and site-specific time-activity patterns and water consumption were
evaluated by using questionnaires for children. Exposure parameters including
outdoor and indoor activity time, ventilation rate and water consumption in this
study were different from the default values of the IEUBK model. Statistical
analysis revealed no significant differences between the predicted and observed
BLLs. Diet and soil/dust lead intake contributed approximately 83.39% (57.40%
93.84% range) and 15.18% (3.25%-41.60% range) of total lead intake, respectively.
These findings showed that the IEUBK model is suitable for lead risk assessment
of Chinese children aged 61-84 months old and diet acts as an important lead
source.
PMID- 26433330
TI - A model-based analysis of SO2 and NO2 dynamics from coal-fired power plants under
representative synoptic circulation types over the Iberian Peninsula.
AB - Emissions of SO2 and NO2 from coal-fired power plants are a significant source of
air pollution. In order to typify the power plants' plumes dynamics and quantify
their contribution to air quality, a comprehensive characterisation of seven coal
fired power plant plumes has been performed under six representative circulation
types (CTs) identified by means of a synoptic classification over the Iberian
Peninsula. The emission and the transport of SO2 and NO2 have been simulated with
the CALIOPE air quality forecasting system that couples the HERMES emission model
for Spain and WRF and CMAQ models. For the facilities located in continental and
Atlantic areas (As Pontes, Abono, and Compostilla) the synoptic advection
controls pollutant transport, however for power plants located along the
Mediterranean or over complex-terrains (Guardo, Andorra, Carboneras, and Los
Barrios), plume dynamics are driven by a combination of synoptic and mesoscale
mountain-valley and sea-land breezes. The contribution of power plants to surface
concentration occurs mainly close to the source (<20 km) related to a fumigation
process when the emission injection takes place within the planetary boundary
layer reaching up to 55 MUg SO2 m(-3) and 32 MUg NO2 m(-3). However, the SO2 and
NO2 plumes can reach long distances (>250 km from the sources) especially for CTs
characterised by Atlantic advection.
PMID- 26433331
TI - Hexabromocyclododecanes, polybrominated diphenyl ethers, and polychlorinated
biphenyls in radiometrically dated sediment cores from English lakes, ~1950
present.
AB - This paper reports input fluxes between ~1950 and present, of polychlorinated
biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and
hexabromocyclododecanes (HBCDs) in radiometrically-dated sediment cores from 7
English lakes. Fluxes of PCBs at all but one location prone to significant
sediment resuspension peaked in the late-1960s/early-1990s, before declining
thereafter. Input fluxes of HBCDs at all sites increased from first emergence in
the mid-1960s. Thereafter, fluxes peaked in the late-1980s/early-2000s, before
declining through to the present, except at the most urban site where HBCD fluxes
are still increasing. Trends of PBDEs predominant in the Penta-BDE and Octa-BDE
formulations vary between sites. While at some locations, fluxes peaked in the
late-1990s/early-2000s; at others, fluxes are still increasing. This suggests the
full impact of EU restrictions on these formulations has yet to be felt. Fluxes
of BDE-209 have yet to peak at all except one location, suggesting little
discernible environmental response to recent EU restrictions on the Deca-BDE
product. Strikingly, fluxes of BDE-209 in the most recent core slices either
exceed or approach peak fluxes of SigmaPCBs, implying substantial UK use of Deca
BDE. Excepting HBCDs, inventories of our target contaminants correlated
significantly with local population density, implying substantial urban sources.
PMID- 26433332
TI - Air pollution and fasting blood glucose: A longitudinal study in China.
AB - Limited studies have examined the associations between air pollutants [particles
with diameters of 10 MUm or less (PM10), sulphur dioxide (SO2), and nitrogen
dioxide (NO2)] and fasting blood glucose (FBG). We collected data for 27,685
participants who were followed during 2006 and 2008. Generalized Estimating
Equation models were used to examine the effects of air pollutants on FBG while
controlling for potential confounders. We found that increased exposure to NO2,
SO2 and PM10 was significantly associated with increased FBG levels in single
pollutant models (p<0.001). For exposure to 4 days' average of concentrations, a
100 MUg/m(3) increase in SO2, NO2, and PM10 was associated with 0.17 mmol/L (95%
CI: 0.15-0.19), 0.53 mmol/L (95% CI: 0.42-0.65), and 0.11 mmol/L (95% CI: 0.07
0.15) increase in FBG, respectively. In the multi-pollutant models, the effects
of SO2 were enhanced, while the effects of NO2 and PM10 were alleviated. The
effects of air pollutants on FBG were stronger in female, elderly, and overweight
people than in male, young and underweight people. In conclusion, the findings
suggest that air pollution increases the levels of FBG. Vulnerable people should
pay more attention on highly polluted days to prevent air pollution-related
health issues.
PMID- 26433333
TI - Temporal variations in embryotoxicity of Lake Ontario American eel (Anguilla
rostrata) extracts to developing Fundulus heteroclitus.
AB - The recruitment of American eel (Anguilla rostrata) juveniles to Lake Ontario
(LO), Canada has declined significantly since the 1980s. To investigate the
possible contribution of maternally-transferred persistent organic pollutants
(POPs) to this decline, this study measured temporal variations in the toxicity
of complex organic mixtures extracted from LO American eels captured in 1988,
1998 and 2008 to developing Fundulus heteroclitus exposed by intravitelline (IVi)
injection. The 1988 and 1998 eel extracts were most toxic, causing a pattern of
sublethal embryotoxic responses similar to those previously reported in F.
heteroclitus embryos exposed to single dioxin-like compounds (DLCs): stunted
growth, craniofacial deformities, EROD activity induction, and reduced predatory
capacities. The potency of extracts declined over time; the only significant
effect of the 2008 eel extracts was EROD induction. The chemically-derived TCDD
TEQs of eel extracts, calculated using measured concentrations of some DLCs and
their relative potencies for F. heteroclitus, overestimated their potency to
induce EROD activity possibly due to interactions among POPs. Other POPs measured
in eel extracts (non-dioxin-like PCBs, PBDEs and organochlorinated pesticides)
did not appear to be important agonistic contributors to the observed toxicity.
The toxicity of the complex mixtures of POPs measured in LO eels may have been
underestimated as a result of several factors, including the loss of POPs during
extracts preparation and a focus only on short-term effects. Based on the model
species examined, our results support the hypothesis that contamination of LO
with DLCs may have represented a threat to the American eel population through
ecologically-relevant effects such as altered larval prey capture ability. These
results prioritize the need to assess early life stage (ELS) toxicity of DLCs in
Anguilla species, to investigate long-term effects of complex eel extracts to ELS
of fish, and to develop biomarkers for potential effects in eel ELS sampled in
the field.
PMID- 26433334
TI - Environmental fate of the fungicide metalaxyl in soil amended with composted
olive-mill waste and its biochar: An enantioselective study.
AB - A large number of pesticides are chiral and reach the environment as mixtures of
optical isomers or enantiomers. Agricultural practices can affect differently the
environmental fate of the individual enantiomers. We investigated how amending an
agricultural soil with composted olive-mill waste (OMWc) or its biochar (BC) at
2% (w:w) affected the sorption, degradation, and leaching of each of the two
enantiomers of the chiral fungicide metalaxyl. Sorption of metalaxyl enantiomers
was higher on BC (Kd ~ 145 L kg(-1)) than on OMWc (Kd ~ 22 L kg(-1)) and was not
enantioselective in either case, and followed the order BC-amended>OMWc
amended>unamended soil. Both enantiomers showed greater resistance to desorption
from BC-amended soil compared to unamended and OMWc-amended soil. Dissipation
studies revealed that the degradation of metalaxyl was more enantioselective
(R>S) in unamended and OMWc-amended soil than in BC-amended soil. The leaching of
both S- and R-metalaxyl from soil columns was almost completely suppressed after
amending the soil with BC and metalaxyl residues remaining in the soil columns
were more racemic than those in soil column leachates. Our findings show that
addition of BC affected the final enantioselective behavior of metalaxyl in soil
indirectly by reducing its bioavailability through sorption, and to a greater
extent than OMWc. BC showed high sorption capacity to remove metalaxyl
enantiomers from water, immobilize metalaxyl enantiomers in soil, and mitigate
the groundwater contamination problems particularly associated with the high
leaching potential of the more persistent enantiomer.
PMID- 26433335
TI - Environmental risk assessment of chemicals and nanomaterials--The best foundation
for regulatory decision-making?
AB - Environmental risk assessment (ERA) is often considered as the most transparent,
objective and reliable decision-making tool for informing the risk management of
chemicals and nanomaterials. ERAs are based on the assumption that it is possible
to provide accurate estimates of hazard and exposure and, subsequently, to
quantify risk. In this paper we argue that since the quantification of risk is
dominated by uncertainties, ERAs do not provide a transparent or an objective
foundation for decision-making and they should therefore not be considered as a
"holy grail" for informing risk management. We build this thesis on the analysis
of two case studies (of nonylphenol and nanomaterials) as well as a historical
analysis in which we address the scientific foundation for ERAs. The analyses
show that ERAs do not properly address all aspects of actual risk, such as the
mixture effect and the environmentally realistic risk from nanomaterials.
Uncertainties have been recognised for decades, and assessment factors are used
to compensate for the lack of realism in ERAs. The assessment factors' values
were pragmatically determined, thus lowering the scientific accuracy of the ERAs.
Furthermore, the default choice of standard assay for assessing a hazard might
not always be the most biologically relevant, so we therefore argue that an ERA
should be viewed as a pragmatic decision-making tool among several, and it should
not have a special status for informing risk management. In relation to other
relevant decision-making tools we discuss the use of chemical alternative
assessments (CAAs) and the precautionary principle.
PMID- 26433336
TI - Tracking progress towards global drinking water and sanitation targets: A within
and among country analysis.
AB - INTRODUCTION: Global access to safe drinking water and sanitation has improved
dramatically during the Millennium Development Goal (MDG) period. However, there
is substantial heterogeneity in progress between countries and inequality within
countries. METHODS: We assessed countries' temporal patterns in access to
drinking water and sanitation using publicly available data. We then classified
countries using non-linear modeling techniques as having one of the following
trajectories: 100% coverage, linear growth, linear decline, no change,
saturation, acceleration, deceleration, negative acceleration, or negative
deceleration. We further assessed the degree to which temporal profiles follow a
sigmoidal pattern and how these patterns might vary within a given country
between rural and urban settings. RESULTS: Among countries with more than 10 data
points, between 15% and 38% showed a non-linear trajectory, depending on the
indicator. Overall, countries' progress followed a sigmoidal trend, but some
countries are making better progress and some worse progress than would be
expected. We highlight several countries that are not on track to meet the MDG
for water or sanitation, but whose access is accelerating, suggesting better
performance during the coming years. Conversely, we also highlight several
countries that have made sufficient progress to meet the MDG target, but in which
access is decelerating. DISCUSSION: Patterns were heterogeneous and non-linearity
was common. Characterization of these heterogeneous patterns will help policy
makers allocate resources more effectively. For example, policy makers can
identify countries that could make use of additional resources or might be in
need of additional institutional capacity development to properly manage
resources; this will be essential to meet the forthcoming Sustainable Development
Goals.
PMID- 26433337
TI - Reply to the Letter to the Editor "High-sensitivity C-reactive protein in obese
children: Too complex a marker to use?".
PMID- 26433338
TI - The impact of response frequency on spatial stimulus-response correspondence
effects.
AB - The present study explored how response preparation, varied by relative response
frequency, affects response conflict as expressed in the Simon effect. Previous
studies showed that valid response cues, when presented before the imperative
stimulus, increase rather than decrease the Simon effect. This finding was
explained by the hypothesis that response cues trigger shifts of attention to the
side of the prepared response, and that these attention shifts modulate
processing of the imperative stimulus. We investigated whether cues are necessary
for inducing shifts of attention and thereby modulating the Simon effect, or
whether response preparation without cues is sufficient. In two experiments,
participants performed a Simon task with one response being more frequent than
the other. Results showed larger Simon effects for the more frequent (i.e.
prepared) response than for the less frequent (i.e. unprepared) response. These
results suggest that response preparation (rather than the cue that induces the
preparation) triggers a shift of spatial attention which modulates the Simon
effect.
PMID- 26433339
TI - CdTe quantum dots@luminol as signal amplification system for chrysoidine with
chemiluminescence-chitosan/graphene oxide-magnetite-molecularly imprinting
sensor.
AB - A sensitive chemiluminescence (CL) sensor based on chemiluminescence resonance
energy transfer (CRET) in CdTe quantum dots@luminol (CdTe QDs@luminol)
nanomaterials combined with chitosan/graphene oxide-magnetite-molecularly
imprinted polymer (Cs/GM-MIP) for sensing chrysoidine was developed. CdTe
QDs@luminol was designed to not only amplify the signal of CL but also reduce
luminol consumption in the detection of chrysoidine. On the basis of the abundant
hydroxy and amino, Cs and graphene oxide were introduced into the GM-MIP to
improve the adsorption ability. The adsorption capacities of chrysoidine by both
Cs/GM-MIP and non-imprinted polymer (Cs/GM-NIP) were investigated, and the CdTe
QDs@luminol and Cs/GM-MIP were characterized by UV-vis, FTIR, SEM and TEM. The
proposed sensor can detect chrysoidine within a linear range of 1.0*10(-7) -
1.0*10(-5) mol/L with a detection limit of 3.2*10(-8) mol/L (3delta) due to
considerable chemiluminescence signal enhancement of the CdTe quantum
dots@luminol detector and the high selectivity of the Cs/GM-MIP system. Under the
optimal conditions of CL, the CdTe QDs@luminol-Cs/GM-MIP-CL sensor was used for
chrysoidine determination in samples with satisfactory recoveries in the range of
90-107%.
PMID- 26433340
TI - pH-dependent plasmonic catalysis of 4-nitrobenzenethiol in aqueous environment.
AB - Plasmon-driven chemical reaction of 4-nitrobenzenethiol (4-NBT) dimerizing to
p,p'-dimercaptoazobenzene (DMAB) has been successfully monitored under different
pH solutions. The experimental results indicated that the chemical reactions were
dependent on the pH values, and they proceeded more completely under acidic
conditions than those under neutral and alkaline conditions. Furthermore, the
rate of the chemical reactions was effectively controlled by exposure time and
incident laser power. The stable pH dependence demonstrated the plasmon-driven
chemical reactions of 4-NBT to DMAB are sensitive to the surrounding environment,
and have wider applications.
PMID- 26433341
TI - A comparison of antioxidative capacities of fruit juices, drinks and nectars, as
determined by EPR and UV-vis spectroscopies.
AB - The differences in the Trolox Equivalent Antioxidant Capacity (TEAC) values at
the same incubation time obtained by two different techniques: electron
paramagnetic resonance (EPR) spectroscopy and ultraviolet visible (UV-vis)
spectroscopy, which use the same antioxidant-free radical reaction mechanism,
were determined for fruit juices, nectars and drinks. For this study, the stable
free radical 1,1-Diphenyl-2-picryl-hydrazyl (DPPH(*)) was used. The antioxidant
capacity was presented in Trolox Equivalents, e.g., MUM trolox per 100 ml of
sample. All of the studied fruit juices, drinks and nectars showed antioxidative
properties. Dependencies between TEAC values and the percent fruit content and
sample color were observed for the studied beverages. It was found that EPR
spectroscopy is the more adequate method for determining TEAC values for these
kinds of samples.
PMID- 26433342
TI - Alteration of human serum albumin tertiary structure induced by glycation.
Spectroscopic study.
AB - The modification of human serum albumin (HSA) structure by non-enzymatic
glycation is one of the underlying factors that contribute to the development of
complications of diabetes and neurodegenerative diseases. The aim of the present
work was to estimate how glycation of HSA altered its tertiary structure. Changes
of albumin conformation were investigated by comparison of glycated (gHSA) and
non-glycated human serum albumin (HSA) absorption spectra, red edge excitation
shift (REES) and synchronous spectra. Effect of glycation on human serum albumin
tertiary structure was also investigated by (1)H NMR spectroscopy. Formation of
gHSA Advanced Glycation End-products (AGEs) caused absorption of UV-VIS light
between 310 nm and 400 nm while for non-glycated HSA in this region no absorbance
has been registered. Analysis of red edge excitation shift effect allowed for
observation of structural changes of gHSA in the hydrophobic pocket containing
the tryptophanyl residue. Moreover changes in the microenvironment of
tryptophanyl and tyrosyl residues brought about AGEs on the basis of synchronous
fluorescence spectroscopy have been confirmed. The influence of glycation process
on serum albumin binding to 5-dimethylaminonaphthalene-1-sulfonamide (DNSA), 2-(p
toluidino) naphthalene-6-sulfonic acid (TNS), has been studied. Fluorescence
analysis showed that environment of both binding site I and II is modified by
galactose glycation.
PMID- 26433343
TI - Electrophoretic mobility of cell nuclei (EMN index) as a biomarker of the
biological aging process: Considering the association between EMN index and age.
AB - The present study examined whether a specific property of cell microstructures
may be useful as a biomarker of aging. Specifically, the association between age
and changes of cellular structures reflected in electrophoretic mobility of cell
nuclei index (EMN index) values across the adult lifespan was examined. This
report considers findings from cross sections of females (n=1273) aged 18-98
years, and males (n=506) aged 19-93 years. A Biotest apparatus was used to
perform intracellular microelectrophoresis on buccal epithelial cells collected
from each individual. EMN index was calculated on the basis of the number of
epithelial cells with mobile nuclei in reference to the cells with immobile
nuclei per 100cells. Regression analyses indicated a significant negative
association between EMN index value and age for men (r=-0.71, p<0.001) and women
(r=-0.60, p<0.001); demonstrating a key requirement that must be met by a
biomarker of aging. The strength of association observed between EMN index and
age for both men and women was encouraging and supports the potential use of EMN
index for determining a biological age of an individual (or a group). In this
study, a new attempt of complex explanation of cellular mechanisms contributing
to age related changes of the EMN index was made. In this study, a new attempt of
complex explanation of cellular mechanisms contributing to age related changes of
the EMN index was made. EMN index has demonstrated potential to meet criteria
proposed for biomarkers of aging and further investigations are necessary.
PMID- 26433344
TI - Primary testicular lymphoma.
PMID- 26433345
TI - Reply from Authors RE "Analysis of the safety profile of treatment with a large
number of shock waves per session in extracorporeal lithotripsy".
PMID- 26433346
TI - Biofilm formation on the surface of polylactide during its biodegradation in
different environments.
AB - The research was aimed at determining the abundance and viability of biofilm
formed on the surface of polylactide (PLA) during its biodegradation in different
environments. It was also aimed at isolating biofilm forming bacteria,
determining their hydrolytic activity and taxonomic status. The first step was to
evaluate PLA biodegradability in lake water, compost and soil, using OxiTop
Control. The next step was to assess the ability of isolated bacteria to form
biofilm in the investigated environments and to evaluate the biofilm structure.
The results indicate that PLA is sensitive to biodegradation in any environment,
particularly in compost. During this process biofilm of high viability was
observed on the surface of PLA. Based on the 16S rRNA gene sequence, the biofilm
forming bacteria were classified as the following species: Acidovorax sp. LW9,
Chryseobacterium sp. LW2, Aeromonas veronii LW8, Arthrobacter aurescens LG2,
Arthrobacter sp. LG12, A. aurescens LG9, Elizabethkingia meningoseptica LK3, A.
aurescens LK9, A. aurescens and LK7. The results show that different bacterial
species formed biofilm of different abundance and hydrolytic activitiy levels.
PMID- 26433347
TI - Enhanced anti-hyperproliferative activity of human thymidylate synthase inhibitor
peptide by solid lipid nanoparticle delivery.
AB - Recently, octapeptide LSCQLYQR (LRp), reducing growth of cis-platinum (cDDP)
resistant ovarian carcinoma cells by inhibiting the monomer-monomer interface of
the human enzyme thymidylate synthase, has been identified. As the peptide is not
able to cross the cell membrane it requires an appropriate delivery system. In
this work the application of SLNs, biocompatible and efficient tools for the
intracellular drug transport, applied especially for lipophilic drugs, was
exploited for the delivery of the hydrophilic peptide LRp. SLNs formulated in the
absence/presence of small amount of squalene showed dimensions below 150 nm,
negative zeta potential and good stability to the freeze-drying process. Even
though the particles formulated with squalene exhibited a less ordered crystal
lattice and a lower surface hydrophobicity, a rapid drug release from these
nanocarriers occurred as a result of the relevant expulsion of the drug from the
lipid core during lipid crystallization. On the contrary, SLNs formulated in the
absence of squalene were able to incorporate more stably the peptide showing
considerable cytotoxic effect on cDDP resistant C13* ovarian carcinoma cell line
at concentration 50 times lower than that used previously with a marketed
delivery system. From the cell cycle analysis by the propidium iodide test in
SLNs-peptide treated cancer cells an increase of apoptosis percentage was
observed, indicating that SLNs were able to carry efficiently the peptide until
its enzymatic target.
PMID- 26433348
TI - Cellular delivery of shRNA using aptamer-conjugated PLL-alkyl-PEI nanoparticles.
AB - Introduction of an efficient gene delivery vector is still the main challenge of
gene therapy. Both polyethylenimine (PEI) and poly(l-lysine) (PLL) comprise
disadvantages which limited their application. To explore whether their
deficiencies could be compensated by preparing copolymers consisting of both PLL
and PEI, we generated several combinations of PLL-alkyl-PEI copolymers conjugated
to aptamer and evaluated their both gene delivery efficiency and down-regulation
of Bcl-XL, an anti-apoptotic gene, in lung cancer cell line. PLL was conjugated
to either 10% or 50% of PEI by grafting different percentages of PEI to alkylated
PLL as core. The properties of modified polymers including size, surface charge
density, DNA condensation ability, buffering capacity and cytotoxicity were
evaluated. According to transfection results, aptamer conjugated PLL-alkyl-10%
PEI (PLPE8%) was selected for further gene silencing study by plasmid shRNA.
Decrease in Bcl-XL gene expression was estimated by both RT-PCR and western-blot
experiments. The obtained results revealed that the new copolymers had
appropriate nano-scale size (117-128 nm) even after aptamer conjugation (168-183
nm). Moreover, they exhibited increased transfection efficiencies by up to 1.8-5
folds and acceptable cytotoxicity. The apoptosis was induced in transfected cells
by shRNA-aptamer-copolymer due to the down-regulation of mRNA and protein levels.
This study suggested a new vector for targeted non-viral gene delivery with high
transfection efficiency in lung cancer or pulmonary systems.
PMID- 26433349
TI - Acid-responsive PEGylated doxorubicin prodrug nanoparticles for neuropilin-1
receptor-mediated targeted drug delivery.
AB - Self-assembled prodrug nanoparticles have demonstrated great promise in cancer
chemotherapy. In the present study, we developed a new kind of prodrug
nanoparticles for targeted drug delivery. PEGylated doxorubicin conjugate with an
acid-cleavable cis-aconityl spacer was prepared. Then it was functionalized with
a tumor-penetrating peptide, Cys-Arg-Gly-Asp-Lys (CRGDK), providing the prodrug
nanoparticles with the specific binding ability to neurophilin-1 receptor. In
acid mediums, doxorubicin could be released from the prodrug nanoparticles with
an accumulative release around 60% through the acid-triggered hydrolysis of cis
aconityl bond and nanoparticle disassembly. Whereas, drug release was slow under
a neutral pH and the accumulative drug release was less than 16%. In the cell
culture tests, our prodrug nanoparticles showed enhanced endocytosis and
cytotoxicity in cancer cells including HepG2, MCF-7 and MDA-MB-231 cells, but
lower cytotoxicity in human cardiomyocyte H2C9. In the animal experiments, the
prodrug nanoparticles were intravenously injected into Balb/c nude mice bearing
MDA-MB-231 tumors. Enhanced drug penetration and accumulation in tumors,
accompanying with a rapid early tumor-binding behavior, was observed after
intravenous injection of the peptide modified prodrug nanoparticles. These data
suggests that the acid-sensitive and tumor-targeting PEGylated doxorubicin
prodrug nanoparticle may be an efficient drug delivery system for cancer
chemotherapy.
PMID- 26433350
TI - Infra-renal abdominal aortic calcification volume does not predict small
abdominal aortic aneurysm growth.
AB - BACKGROUND: Vascular calcification is a common finding in abdominal aortic
aneurysms (AAA) however whether it predicts aneurysm expansion is controversial.
OBJECTIVES: 1) To establish a reproducible method of assessing AAA calcification
using computed tomography (CT); 2) To investigate the association between AAA
calcification and growth. METHOD: Patients were identified from a prospectively
maintained small AAA surveillance database. To be included patients required at
least two CT scans a minimum of 6 months apart. All patients had a maximal AAA
diameter of <=55 mm on their initial scan. Infra-renal aortic calcification
volume, total infra-renal aortic volume and maximal AAA diameter were measured.
Reproducibility was assessed from repeat scans performed on 31 patients. AAA
growth, estimated by volume change per year, was compared between patients with
baseline infra-renal aortic calcification volumes< and >=median. RESULTS: 95%
agreement limits (lower, upper) for intra and inter-observer error in measuring
infra-renal aortic calcification volume were 0.68, 97 mm(3) and -140, 5.8 mm(3),
respectively. Concordance correlation coefficients for inter and intra-observer
variability in measuring infra-renal aortic calcification volume were 0.99 and
0.99, respectively. Patients with infra-renal aortic calcification volume <
median (n = 44) and >=median (n = 44) had an infra-renal aortic volume increase
of 6.0 cm(3)/yr and 7.8 cm(3)/yr, respectively (p = 0.66). Mean percentage infra
renal aortic volume increase/yr was found to be 4.2 +/- 6.4 and 8.9 +/- 6.2 for
patients with and without diabetes, respectively (p = 0.003). CONCLUSION: Infra
renal aortic calcification volume can be assessed reproducibly from CT images.
Infra-renal aortic calcification volume did not predict small AAA growth.
PMID- 26433352
TI - Electrochemical lateral flow immunosensor for detection and quantification of
dengue NS1 protein.
AB - An Electrochemical Lateral Flow Immunosensor (ELFI) is developed combining screen
printed gold electrodes (SPGE) enabling quantification together with the
convenience of a lateral flow test strip. A cellulose glassy fiber paper
conjugate pad retains the marker immunoelectroactive nanobeads which will bind to
the target analyte of interest. The specific immunorecognition event continues to
occur along the lateral flow bed until reaching the SPGE-capture antibodies at
the end of the cellulosic lateral flow strip. The rationale of the immunoassay
consists in the analyte antigen NS1 protein being captured selectively and
specifically by the dengue NS1 antibody conjugated onto the immunonanobeads thus
forming an immunocomplex. With the aid of a running buffer, the immunocomplexes
flow and reach the immuno-conjugated electrode surface and form specific sandwich
type detection due to specific, molecular recognition, while unbound beads move
along past the electrodes. The successful sandwich immunocomplex formation is
then recorded electrochemically. Specific detection of NS1 is translated into an
electrochemical signal contributed by a redox label present on the bead
immobilized detection dengue NS1 antibody while a proportional increase of
faradic current is observed with increase in analyte NS1 protein concentration.
The first generation ELFI prototype is simply assembled in a cassette and
successfully demonstrates wide linear range over a concentration range of 1-25
ng/mL with an ultrasensitive detection limit of 0.5 ng/mL for the qualitative and
quantitative detection of analyte dengue NS1 protein.
PMID- 26433353
TI - Colon-derived uremic biomarkers induced by the acute toxicity of Kansui radix: A
metabolomics study of rat plasma and intestinal contents by UPLC-QTOF-MS(E).
AB - Kansui radix (KR) is a poisonous Chinese herbal medicine recorded in the Chinese
Pharmacopoeia, and the acute toxicity obstructs its clinical applications. To
explore its acute toxicity mechanism to enhance clinical safety, a metabolomics
study based on UPLC-ESI-QTOF-MS(E) was performed. Wistar rats were exposed for 4h
to the aqueous and ethyl acetate extracts prepared from KR at a high dose
(25g/kg). The contents of six different sections of rat intestine, including the
duodenum, jejunum, ileum, cecum, colon, and rectum were collected as samples for
the first time, as well as the rat plasma. The interesting results showed that
only those rats exposed to the ethyl acetate extract showed a watery diarrhea,
similar to the observed acute human toxicity. The identified biomarkers found in
the plasma, such as phenol sulfate, indoxyl sulfate, and p-cresol sulfate were
significantly perturbed in the rats. These biomarkers are known as colon-derived
uremic compounds, which were first reported with respect to KR. The three
essential amino acids which produced these biomarkers were only found in the
contents of colon and rectum. A hypothesis was proposed that only the colon
derived uremic compounds induced by KR might be responsible for the acute
toxicity. Three traditional process methods to reduce the toxicity of KR were
compared based on these biomarkers, and different levels of toxicity modulation
were observed. These results may be helpful to further understand the mechanism
of acute toxicity, and the relevance of the traditional process methods to
ameliorate the adverse effects of KR.
PMID- 26433351
TI - Linkage analyses in Caribbean Hispanic families identify novel loci associated
with familial late-onset Alzheimer's disease.
AB - INTRODUCTION: We performed linkage analyses in Caribbean Hispanic families with
multiple late-onset Alzheimer's disease (LOAD) cases to identify regions that may
contain disease causative variants. METHODS: We selected 67 LOAD families to
perform genome-wide linkage scan. Analysis of the linked regions was repeated
using the entire sample of 282 families. Validated chromosomal regions were
analyzed using joint linkage and association. RESULTS: We identified 26 regions
linked to LOAD (HLOD >=3.6). We validated 13 of the regions (HLOD >=2.5) using
the entire family sample. The strongest signal was at 11q12.3 (rs2232932: HLODmax
= 4.7, Pjoint = 6.6 * 10(-6)), a locus located ~2 Mb upstream of the membrane
spanning 4A gene cluster. We additionally identified a locus at 7p14.3
(rs10255835: HLODmax = 4.9, Pjoint = 1.2 * 10(-5)), a region harboring genes
associated with the nervous system (GARS, GHRHR, and NEUROD6). DISCUSSION: Future
sequencing efforts should focus on these regions because they may harbor familial
LOAD causative mutations.
PMID- 26433355
TI - Stability of saliva microbiota during moderate consumption of red wine.
AB - OBJECTIVE: This study has evaluated the effect of regular and moderate red wine
consumption on the diversity and occurrence of different groups of bacteria that
are representative in human saliva. METHODS: Saliva from twenty-two healthy
volunteers (age range 20-48 years) was analyzed in this study. Fourteen
individuals consumed red wine (250mL/day) during 4 weeks, whereas 8 volunteers
were included in the control group. The evolution and composition of the
microbial community in saliva was evaluated by PCR-DGGE and quantitative PCR.
RESULTS: The microbial inter-individual variability observed in the PCR-DGGE band
patterns was higher than the differences observed after the 4-weeks period of red
wine intake. Bifidobacterium dentium, Bifidobacterium spp. and Alloscardovia
omnicolens were the most representative bifidobacterial species, whereas the
Streptococcus mitis-Streptococcus oralis group predominated within Streptococcus.
This genus was the most numerous of the bacterial groups assayed, reaching
average counts above 8 log copy numbers/mL. On the other hand, the lowest counts
were recorded for Actinomyces, Fusobacterium, Haemophilus, Neisseria and
Veillonella, which showed average values of 5 log copy numbers/mL. The results
showed no significant differences (P>0.5) in bacterial counts after the period of
red wine intake. CONCLUSION: The overall diversity and stability of
representative bacterial groups of the human saliva is not disturbed due to
regular-moderate red wine consumption.
PMID- 26433354
TI - Identifying genetic determinants of autoimmunity and immune dysregulation.
AB - Common autoimmune diseases are relatively heterogeneous with both genetic and
environmental factors influencing disease susceptibility and progression. As the
populations in developed countries age, these chronic diseases will become an
increasing burden in human suffering and health care costs. By contrast, rare
immune diseases that are severe and develop early in childhood are frequently
monogenic and fully penetrant, often with a Mendelian inheritance pattern.
Although these may be incompatible with survival or cured by hematopoietic stem
cell transplantation, we will argue that they constitute a rich source of genetic
insights into immunological diseases. Here, we discuss five examples of well
studied Mendelian disease-causing genes and their known or predicted roles in
conferring susceptibility to common, polygenic diseases of autoimmunity.
Mendelian disease mutations, as experiments of nature, reveal human loci that are
indispensable for immune regulation and, therefore, most promising as therapeutic
targets.
PMID- 26433356
TI - Modelling contaminant transport for pumping wells in riverbank filtration
systems.
AB - Analytical study of the influence of both the pumping well discharge rate and
pumping time on contaminant transport and attenuation is significant for
hydrological and environmental science applications. This article provides an
analytical solution for investigating the influence of both pumping time and
travelling time together for one-dimensional contaminant transport in riverbank
filtration systems by using the Green's function approach. The basic aim of the
model is to understand how the pumping time and pumping rate, which control the
travelling time, can affect the contaminant concentration in riverbank filtration
systems. Results of analytical solutions are compared with the results obtained
using a MODFLOW numerical model. Graphically, it is found that both analytical
and numerical solutions have almost the same behaviour. Additionally, the graphs
indicate that any increase in the pumping rate or simulation pumping time should
increase the contamination in groundwater. The results from the proposed
analytical model are well matched with the data collected from a riverbank
filtration site in France. After this validation, the model is then applied to
the first pilot project of a riverbank filtration system conducted in Malaysia.
Sensitivity analysis results highlight the importance of degradation rates of
contaminants on groundwater quality, for which higher utilization rates lead to
the faster consumption of pollutants.
PMID- 26433357
TI - A greenhouse trial to investigate the ameliorative properties of biosolids and
plants on physicochemical conditions of iron ore tailings: Implications for an
iron ore mine site remediation.
AB - An iron ore mine site in Swaziland is currently (2015) in a derelict state as a
consequence of past (1964-1988) and present (2011 - current) iron ore mining
operations. In order to control problems associated with mine wastes, the
Swaziland Water Services Corporation (SWSC) recently (2013) proposed the
application of biosolids in sites degraded by mining operations. It is thought
that this practice could generally improve soil conditions and enhance plant
reestablishment. More importantly, the SWSC foresees this as a potential solution
to the biosolids disposal problems. In order to investigate the effects of
biosolids and plants in soil physicochemical conditions of iron mine soils, we
conducted two plant growth trials. Trial 1 consisted of tailings that received
biosolids and topsoil (TUSB mix) while in trial 2, tailings received biosolids
only (TB mix). In the two trials, the application rates of 0 (control), 10, 25,
50, 75 and 100 t ha(-1) were used. After 30 days of equilibration, 25 seeds of
Cynodon dactylon were sown in each pot and thinned to 10 plants after 4 weeks.
Plants were watered twice weekly and remained under greenhouse conditions for 12
weeks, subsequent to which soils were subjected to chemical analysis. According
to the results obtained, there were significant improvements in soil parameters
related to fertility such as organic matter (OM), water holding capacity (WHC),
cation exchange capacity (CEC), ammonium [Formula: see text] , magnesium
(Mg(2+)), calcium (Ca(2+)) and phosphorus ( [Formula: see text] ). With regard to
heavy metals, biosolids led to significant increases in soil total concentrations
of Cu, Zn, Cd, Hg and Pb. The higher concentrations of Zn and Cu in treated
tailings compared to undisturbed adjacent soils are a cause for concern because
in the field, this might work against the broader objectives of mine soil
remediation, which include the recolonization of reclaimed sites by soil-dwelling
organisms. Therefore, while biosolids contain important nutrients that may
greatly improve physicochemical conditions and enhance vegetation reestablishment
in mined soils, the threat of the build-up of higher levels of trace elements in
treated tailings compared to surrounding adjacent soils must not be
underestimated.
PMID- 26433358
TI - Recovery of Zn from acid mine water and electric arc furnace dust in an
integrated process.
AB - In this paper, the purification of acid mine water and the treatment of electric
arc furnace dust (EAFD) are integrated into one process with the aim of
recovering the Zn content of both effluent and waste. Zinc recovery can reduce
the cost of their environmental management: purified acid mine water is
discharged after removing all metals; EAFD ceases to be hazardous waste; and Zn
is valorised. The process consists of the recovery of Zn as zinc oxide and its
purification into commercial products. First, EAFD is leached with acid water and
the dissolved metals are selectively precipitated as hydroxides. After EADF
leaching, ferrous iron is bio-oxidized and Fe and Al are then precipitated; in
the following stage, Cu, Ni, Co and Cd are cemented and finally Zn is
precipitated as ZnO. In order to purify water that finally is discharged to a
river, lime is used as the neutralizing agent, which results in a precipitate of
mainly gypsum, MnO, and ZnO. From the impure zinc oxide produced, various
alternatives for the attainment of commercial products, such as basic zinc
carbonate and electrolytic zinc, are studied in this work.
PMID- 26433359
TI - Evaluation of rhamnolipid (RL) as a biosurfactant for the removal of chromium
from aqueous solutions by precipitate flotation.
AB - Rhamnolipid (RL) is a biosurfactant which is produced by the bacterial species
Pseudomonas aeruginosa. Although applications of this material have been examined
in various fields, its applications in the flotation of heavy metals remain to be
explored. In this research, rhamnolipid was applied as a collector in the
flotation of Cr(III) from aqueous solutions. FeSO4 was used for the precipitation
of Cr(VI) to Cr(III) which was subsequently removed by flotation. A two level
full factorial design (with center points) was used to evaluate the effects of
pH, air flow rate, RL/Cr and Fe/Cr molar ratios on the performance of the
flotation system. The results showed that the biosurfactant was highly effective
in the removal of chromium, and all of the factors had significant effects on the
flotation performance. The chromium removal efficiencies of greater than 95% were
obtained with the initial chromium concentration of 40 ppm within 5 min. Kinetic
studies showed that a first order kinetic model was appropriate to describe the
precipitate flotation of Cr(III) using rhamnolipid as a collector. The
interference of NaCl, CaCl2, CaSO4, and CaCO3 on the Cr removal was also
investigated, and it was demonstrated that CaSO4 and CaCO3 as sparingly water
soluble salts, and CaCl2 as a contributor to water hardness had significant
negative impacts on Cr removal efficiency of rhamnolipid.
PMID- 26433360
TI - Shale gas wastewater management under uncertainty.
AB - This work presents an optimization framework for evaluating different wastewater
treatment/disposal options for water management during hydraulic fracturing (HF)
operations. This framework takes into account both cost-effectiveness and system
uncertainty. HF has enabled rapid development of shale gas resources. However,
wastewater management has been one of the most contentious and widely publicized
issues in shale gas production. The flowback and produced water (known as FP
water) generated by HF may pose a serious risk to the surrounding environment and
public health because this wastewater usually contains many toxic chemicals and
high levels of total dissolved solids (TDS). Various treatment/disposal options
are available for FP water management, such as underground injection, hazardous
wastewater treatment plants, and/or reuse. In order to cost-effectively plan FP
water management practices, including allocating FP water to different options
and planning treatment facility capacity expansion, an optimization model named
UO-FPW is developed in this study. The UO-FPW model can handle the uncertain
information expressed in the form of fuzzy membership functions and probability
density functions in the modeling parameters. The UO-FPW model is applied to a
representative hypothetical case study to demonstrate its applicability in
practice. The modeling results reflect the tradeoffs between economic objective
(i.e., minimizing total-system cost) and system reliability (i.e., risk of
violating fuzzy and/or random constraints, and meeting FP water
treatment/disposal requirements). Using the developed optimization model,
decision makers can make and adjust appropriate FP water management strategies
through refining the values of feasibility degrees for fuzzy constraints and the
probability levels for random constraints if the solutions are not satisfactory.
The optimization model can be easily integrated into decision support systems for
shale oil/gas lifecycle management.
PMID- 26433361
TI - Risk analysis of emergent water pollution accidents based on a Bayesian Network.
AB - To guarantee the security of water quality in water transfer channels, especially
in open channels, analysis of potential emergent pollution sources in the water
transfer process is critical. It is also indispensable for forewarnings and
protection from emergent pollution accidents. Bridges above open channels with
large amounts of truck traffic are the main locations where emergent accidents
could occur. A Bayesian Network model, which consists of six root nodes and three
middle layer nodes, was developed in this paper, and was employed to identify the
possibility of potential pollution risk. Dianbei Bridge is reviewed as a typical
bridge on an open channel of the Middle Route of the South to North Water
Transfer Project where emergent traffic accidents could occur. Risk of water
pollutions caused by leakage of pollutants into water is focused in this study.
The risk for potential traffic accidents at the Dianbei Bridge implies a risk for
water pollution in the canal. Based on survey data, statistical analysis, and
domain specialist knowledge, a Bayesian Network model was established. The human
factor of emergent accidents has been considered in this model. Additionally,
this model has been employed to describe the probability of accidents and the
risk level. The sensitive reasons for pollution accidents have been deduced. The
case has also been simulated that sensitive factors are in a state of most likely
to lead to accidents.
PMID- 26433362
TI - Optimisation of sludge pretreatment by low frequency sonication under pressure.
AB - This work aims at optimizing sludge pretreatment by non-isothermal sonication,
varying frequency, US power (PUS) and intensity (IUS varied through probe size),
as well as hydrostatic pressure and operation mode (continuous vs. sequential -
or pulsed - process). Under non isothermal sonication sludge solubilization
results from both ultrasound disintegration and thermal hydrolysis which are
conversely depending on temperature. As found in isothermal operation: - For a
given specific energy input, higher sludge disintegration is still achieved at
higher PUS and lower sonication time. - US effects can be highly improved by
applying a convenient pressure. - 12 kHz always performs better than 20 kHz.
Nevertheless the optimum pressure depends not only on PUS and IUS, but also on
temperature evolution during sonication. Under adiabatic mode, a sequential
sonication using 5 min US-on at 360 W, 12 kHz, and 3.25 bar and 30 min US-off
gives the best sludge disintegration, while maintaining temperature in a
convenient range to prevent US damping.
PMID- 26433363
TI - Pilot-scale study on the treatment of basal aquifer water using ultrafiltration,
reverse osmosis and evaporation/crystallization to achieve zero-liquid discharge.
AB - Basal aquifer water is deep groundwater found at the bottom of geological
formations, underlying bitumen-saturated sands. Some of the concerns associated
with basal aquifer water at the Athabasca oil sands are the high concentrations
of hardness-causing compounds, alkalinity, and total dissolved solids. The
objective of this pilot-scale study was to treat basal aquifer water to a quality
suitable for its reuse in the production of synthetic oil. To achieve zero-liquid
discharge (ZLD) conditions, the treatment train included chemical oxidation,
polymeric ultrafiltration (UF), reverse osmosis (RO), and evaporation
crystallization technologies. The results indicated that the UF unit was
effective in removing solids, with UF filtrate turbidity averaging 2.0 NTU and
silt density index averaging 0.9. Membrane autopsies indicated that iron was the
primary foulant on the UF and RO membranes. Laboratory and pilot-scale tests on
RO reject were conducted to determine the feasibility of ZLD crystallization. Due
to the high amounts of calcium, magnesium, and bicarbonate in the RO reject,
softening of the feed was required to avoid scaling in the evaporator. Crystals
produced throughout the testing were mainly sodium chloride. The results of this
study indicated that the ZLD approach was effective in both producing freshwater
and minimizing brine discharges.
PMID- 26433364
TI - Smoking, passive smoking and lung cancer cell types among women in Morocco:
analysis of epidemiological profiling of 101 cases.
AB - BACKGROUND: Recently women's lung cancer mortality rates have dramatically
increased in developed countries, contrasting with a levelling off or decrease
among men. Descriptive epidemiological data on primary lung cancer in women is
scarce in Morocco. The aim of this study, conducted in the National Institute of
Oncology in Rabat, was to describe the epidemiological profiling especially for
the smoking status, to determine the most frequent type of lung cancer, and to
analyse the survival of Moroccan women with lung cancer diagnosis. RESULTS: We
found 101 women among 1680 (male and female) cases of lung cancer. The never
smokers were estimated to 75 %. The proportion of adenocarcinoma among never and
passive smokers was higher than that of squamous cell carcinoma (SCC) (69.4
versus 30.6 %), while among women who were smokers, the most frequent
histological type was SCC (63.6 %). The Cox regression analysis showed that
smoking and passive smoking were not significantly associated with survival [HR:
0.62 (95 % CI 0.31, 1.30); p = 0.19] [HR: 0.56 (95 % CI 0.29, 1.08); p = 0.08]
respectively. Adenocarcinoma was significantly associated with shorter survival
[HR: 1.73 (95 % CI 1.05, 2.85); p = 0.03]. CONCLUSIONS: The majority Moroccan
women affected by lung cancer have never smoked (75 %). Environmental exposures,
genetic predisposition, hormonal factors, and viral infection may all play a role
in lung cancer in this category. The relation between histological type and
tobacco found in our series concurred with those reported in the literature-
adenocarcinoma appears to be the most frequent cell type affecting never and
passive smokers. Adenocarcinoma is significantly associated with poorer survival.
PMID- 26433365
TI - Development of nitric oxide catalytic coatings by conjugating 3,3
disulfodipropionic acid and 3,3-diselenodipropionic acid for improving
hemocompatibility.
AB - Nitric oxide (NO), discovered as an endothelium-derived relaxing factor, has been
found to have multiple intracellular effects in vascular diseases including
vasorelaxation regulation, endothelial regeneration, inhibition of leukocyte
chemotaxis, and platelet activation. In the work described here, the authors have
developed a NO-catalytic bioactive coating for improving hemocompatibility. The
authors first prepared a dopamine and hexamethylendiamine (PDAM/HD) amine-rich
adherent copolymer coating to introduce amine groups onto 316L stainless steel,
followed by covalently conjugating 3,3-disulfodipropionic acid (S-S) and 3,3
diselenodipropionic acid (Se-Se), which mimic glutathione peroxidase-like
catalytic production of NO. S-S and Se-Se were immobilized on the PDAM/HD surface
via carbodiimide coupling chemistry. X-ray photoelectron spectroscopy analysis
revealed clear S2p and Se3d signals, confirming the immobilization of S-S and Se
Se on the PDAM/HD surface. The NO release behavior of different samples was
investigated. In detail, two species of thionitrites (RSNO), S-nitrosoglutathione
(GSNO, endogenous NO donors) and S-nitrosoacetylpenicillamine (SNAP) were chosen
as NO donors to investigate the NO catalytic properties of S-S and Se-Se modified
PDAM/HD surfaces. Not only Se-Se@PDAM/HD but also S-S@PDAM/HD coatings showed the
ability to continuously catalyze RSNO to generate NO in the presence of proper
thiol reducing agent. For the Se-Se@PDAM/HD coating, the NO release amount and
rate were greater than S-S@PDAM/HD in both GSNO and SNAP conditions. The results
showed that organosulfide species possesses NO catalytic ability as well as
organoselenium species. The authors demonstrated that both S-S@PDAM/HD and Se
Se@PDAM/HD coatings exhibited outstanding inhibition effect on platelet adhesion,
aggregation and activation via the cyclic guanylate monophosphate signal pathway.
Thus these results suggested that NO catalytic coatings based on organoselenium
and organosulfide species immobilization can help to improve hemocompatibility.
NO-catalytic strategies possess huge potential applications in blood-contacting
devices.
PMID- 26433366
TI - Modulation of cationicity of chitosan for tuning mesenchymal stem cell adhesion,
proliferation, and differentiation.
AB - The aim of this study was to modulate the cationicity of chitosan to influence
the mesenchymal stem cell (MSC) responses in terms of cell adhesion,
proliferation, and differentiation. The authors prepared water-soluble
carboxymethyl chitosan hydrogels using genipin as the crosslinking agent. The
chitosan cationicity was modulated by varying the genipin content from 0.5 to 10
wt. %. The results indicated that the cationicity exerted a striking modulation
effect on various MSC responses. The increase of the genipin content, i.e.,
decrease of the free amino group content (cationicity), overall promoted the MSC
adhesion, cytoskeleton organization, proliferation, and differentiation into the
osteogenic lineage. A surprising cell alignment effect was also observed on
chitosan samples with high genipin concentrations (>2.5%). The chitosan sample
with the highest genipin concentrations (10%) exhibited the best MSC
proliferation and highest protein expression levels toward osteogenic lineages.
The genipin content also showed a strong modulation effect on MSC condensation,
and cell-cell and cell-matrix interactions, as suggested by the expressions of
the sry related HMG box9 (Sox9), intercellular adhesion molecule 1, and N
Cadherin. Overall, the authors have demonstrated that modulation of cationicity
(amino content) of chitosan is an effective and simple approach to tuning various
MSC responses, including adhesion, proliferation, differentiation, as well as
cell-cell interactions. Such findings might have important implications in
biomaterial design for various biomedical applications.
PMID- 26433367
TI - High-risk plaque features can be detected in non-stenotic carotid plaques of
patients with ischaemic stroke classified as cryptogenic using combined (18)F-FDG
PET/MR imaging.
AB - PURPOSE: The aim of this study was to investigate in 18 patients with ischaemic
stroke classified as cryptogenic and presenting non-stenotic carotid
atherosclerotic plaques the morphological and biological aspects of these plaques
with magnetic resonance imaging (MRI) and (18)F-fluoro-deoxyglucose positron
emission tomography ((18)F-FDG PET) imaging. METHODS: Carotid arteries were
imaged 150 min after injection of (18)F-FDG with a combined PET/MRI system.
American Heart Association (AHA) lesion type and plaque composition were
determined on consecutive MRI axial sections (n = 460) in both carotid arteries.
(18)F-FDG uptake in carotid arteries was quantified using tissue to background
ratio (TBR) on corresponding PET sections. RESULTS: The prevalence of complicated
atherosclerotic plaques (AHA lesion type VI) detected with high-resolution MRI
was significantly higher in the carotid artery ipsilateral to the ischaemic
stroke as compared to the contralateral side (39 vs 0 %; p = 0.001). For all
other AHA lesion types, no significant differences were found between ipsilateral
and contralateral sides. In addition, atherosclerotic plaques classified as high
risk lesions with MRI (AHA lesion type VI) were associated with higher (18)F-FDG
uptake in comparison with other AHA lesions (TBR = 3.43 +/- 1.13 vs 2.41 +/-
0.84, respectively; p < 0.001). Furthermore, patients presenting at least one
complicated lesion (AHA lesion type VI) with MRI showed significantly higher
(18)F-FDG uptake in both carotid arteries (ipsilateral and contralateral to the
stroke) in comparison with carotid arteries of patients showing no complicated
lesion with MRI (mean TBR = 3.18 +/- 1.26 and 2.80 +/- 0.94 vs 2.19 +/- 0.57,
respectively; p < 0.05) in favour of a diffuse inflammatory process along both
carotid arteries associated with complicated plaques. CONCLUSION: Morphological
and biological features of high-risk plaques can be detected with (18)F-FDG
PET/MRI in non-stenotic atherosclerotic plaques ipsilateral to the stroke,
suggesting a causal role for these plaques in stroke. Combined (18)F-FDG PET/MRI
systems might help in the evaluation of patients with ischaemic stroke classified
as cryptogenic.
PMID- 26433368
TI - Changes in the activities of starch metabolism enzymes in rice grains in response
to elevated CO2 concentration.
AB - The global atmospheric CO(2) concentration is currently (2012) 393.1 MUmol mol(
1), an increase of approximately 42 % over pre-industrial levels. In order to
understand the responses of metabolic enzymes to elevated CO(2) concentrations,
an experiment was conducted using the Free Air CO(2) Enrichment (FACE )system.
Two conventional japonica rice varieties (Oryza sativa L. ssp. japonica) grown in
North China, Songjing 9 and Daohuaxiang 2, were used in this study. The
activities of ADPG pyrophosphorylase, soluble and granule-bound starch synthases,
and soluble and granule-bound starch branching enzymes were measured in rice
grains, and the effects of elevated CO(2) on the amylose and protein contents of
the grains were analyzed. The results showed that elevated CO(2) levels
significantly increased the activity of ADPG pyrophosphorylase at day 8, 24, and
40 after flower, with maximum increases of 56.67 % for Songjing 9 and 21.31 % for
Daohuaxiang 2. Similarly, the activities of starch synthesis enzymes increased
significantly from the day 24 after flower to the day 40 after flower, with
maximum increases of 36.81 % for Songjing 9 and 66.67 % for Daohuaxiang 2 in
soluble starch synthase (SSS), and 25.00 % for Songjing 9 and 36.44 % for
Daohuaxiang 2 in granule-bound starch synthase (GBSS), respectively. The elevated
CO(2) concentration significantly increased the activity of soluble starch
branching enzyme (SSBE) at day 16, 32, and 40 after flower, and also
significantly increased the activity of granule-bound starch branching enzyme
(GBSBE) at day 8, 32, and 40 after flower. The elevated CO(2) concentration
increased the peak values of enzyme activity, and the timing of the activity
peaks for SSS and GBSBE were earlier in Songjing 9 than in Daohuaxiang 2. There
were obvious differences in developmental stages between the two varieties of
rice, which indicated that the elevated CO(2) concentration increased enzyme
activity expression and starch synthesis, affecting the final contents of starch
and protein in the rice grains. Our results will provide a foundation for
understanding the physiological mechanisms of rice yield under elevated
atmospheric CO(2) concentrations.
PMID- 26433369
TI - One-year follow-up of two novel CBTs for adolescents with ADHD.
AB - Long-term effects of two CBTs for adolescents with ADHD are explored: One aimed
at improving planning skills (Plan My Life; PML), the other a solution-focused
therapy (SFT) without focusing on planning skills. In a RCT, adolescents with
ADHD (n = 159) were assigned to PML or SFT and improved significantly between pre
and posttest with large effect sizes Boyer et al (Eur Child Adolesc Psychiatry.
doi: 10.1007/s00787-014-0661-5 ), with marginal differences in favor of PML. One
year follow-up data were gathered. Initial improvements remained stable or
continued to improve from posttest to 1-year follow-up. 25.9 % of adolescents
showed normalized functioning. However, no treatment differences were found.
These results are consistent with the finding that treatment of ADHD improves
long-term outcomes, but not to the point of normalization. Earlier found
differences at 3-month follow-up in favor of PML disappeared, indicating that
focusing treatment on planning skills is not necessary for improvement or that a
more prolonged planning-focused treatment is needed.
PMID- 26433371
TI - A dynamic ambulance management model for rural areas : Computing redeployment
actions for relevant performance measures.
AB - We study the Dynamic Ambulance Management (DAM) problem in which one tries to
retain the ability to respond to possible future requests quickly when ambulances
become busy. To this end, we need models for relocation actions for idle
ambulances that incorporate different performance measures related to response
times. We focus on rural regions with a limited number of ambulances. We model
the region of interest as an equidistant graph and we take into account the
current status of both the system and the ambulances in a state. We do not
require ambulances to return to a base station: they are allowed to idle at any
node. This brings forth a high degree of complexity of the state space.
Therefore, we present a heuristic approach to compute redeployment actions. We
construct several scenarios that may occur one time-step later and combine these
scenarios with each feasible action to obtain a classification of actions. We
show that on most performance indicators, the heuristic policy significantly
outperforms the classical compliance table policy often used in practice.
PMID- 26433370
TI - Salivary oxytocin in adolescents with conduct problems and callous-unemotional
traits.
AB - Callous-unemotional (CU) traits correlate with the severity and prognosis of
conduct disorder in youth. The neuropeptide oxytocin (OT) has been linked to
prosocial behaviors, including empathy and collaboration with others. This study
discusses a possible role for OT in the biology of delinquent behavior. We
hypothesized that in delinquent youth OT secretion will correlate with the
severity of conduct problems and specifically with the level of CU traits. The
study group included 67 male adolescents (mean age 16.2 years) undergoing
residential treatment, previously assessed by an open clinical interview and
history for the psychiatric diagnosis. Staff based Inventory of Callous
Unemotional traits for psychopathy and Strength and Difficulties Questionnaire
were administered, and patients' medical and social personal files were
systematically coded for previous history of antisocial acts using the Brown
Goodwin Questionnaire. Salivary OT was assayed by ELISA. Salivary OT levels were
inversely correlated with conduct problems severity on Strength and Difficulties
Questionnaire (r = -0.27; p <= 0.01). Recorded history of antisocial acts did not
correlate with current OT levels. Odds ratio (OR) for significant CU traits among
subjects with conduct problems was increased in low-OT (OR = 14, p <= 0.05) but
not in high-OT subjects (OR = 6, p >= 0.05). Children with conduct problems and
low levels of salivary OT are at risk for significant CU traits. These results
suggest a possible role for salivary OT as a biomarker for CU traits and conduct
problems severity.
PMID- 26433372
TI - Overutilization and underutilization of operating rooms - insights from
behavioral health care operations management.
AB - The planning of surgery durations is crucial for efficient usage of operating
theaters. Both planning too long and too short durations for surgeries lead to
undesirable consequences, e.g. idle time, overtime, or rescheduling of surgeries.
We define these consequences as operating room inefficiency. The overall
objective of planning surgery durations is to minimize expected operating room
inefficiency, since surgery durations are stochastic. While most health care
studies assume economically rational behavior of decision makers, experimental
studies have shown that decision makers often do not act according to economic
incentives. Based on insights from health care operations management, medical
decision making, behavioral operations management, as well as empirical
observations, we derive hypotheses that surgeons' behavior deviates from
economically rational behavior. To investigate this, we undertake an experimental
study where experienced surgeons are asked to plan surgeries with uncertain
durations. We discover systematic deviations from optimal decision making and
offer behavioral explanations for the observed biases. Our research provides new
insights to tackle a major problem in hospitals, i.e. low operating room
utilization going along with staff overtime.
PMID- 26433373
TI - Long-Range Reduced Predictive Information Transfers of Autistic Youths in EEG
Sensor-Space During Face Processing.
AB - The majority of previous functional/effective connectivity studies conducted on
the autistic patients converged to the underconnectivity theory of ASD: "long
range underconnectivity and sometimes short-rang overconnectivity". However, to
the best of our knowledge the total (linear and nonlinear) predictive information
transfers (PITs) of autistic patients have not been investigated yet. Also, EEG
data have rarely been used for exploring the information processing deficits in
autistic subjects. This study is aimed at comparing the total (linear and
nonlinear) PITs of autistic and typically developing healthy youths during human
face processing by using EEG data. The ERPs of 12 autistic youths and 19 age
matched healthy control (HC) subjects were recorded while they were watching
upright and inverted human face images. The PITs among EEG channels were
quantified using two measures separately: transfer entropy with self-prediction
optimality (TESPO), and modified transfer entropy with self-prediction optimality
(MTESPO). Afterwards, the directed differential connectivity graphs (dDCGs) were
constructed to characterize the significant changes in the estimated PITs of
autistic subjects compared with HC ones. By using both TESPO and MTESPO, long
range reduction of PITs of ASD group during face processing was revealed
(particularly from frontal channels to right temporal channels). Also, it seemed
the orientation of face images (upright or upside down) did not modulate the
binary pattern of PIT-based dDCGs, significantly. Moreover, compared with TESPO,
the results of MTESPO were more compatible with the underconnectivity theory of
ASD in the sense that MTESPO showed no long-range increase in PIT. It is also
noteworthy that to the best of our knowledge it is the first time that a version
of MTE is applied for patients (here ASD) and it is also its first use for EEG
data analysis.
PMID- 26433374
TI - Money and Mental Illness: A Study of the Relationship Between Poverty and Serious
Psychological Problems.
AB - Several studies have indicated a co-occurrence between mental problems, a bad
economy, and social isolation. Medical treatments focus on reducing the extent of
psychiatric problems. Recent research, however, has highlighted the possible
effects of social initiatives. The aim of this study was to examine the relation
between severe mental illness, economic status, and social relations. METHOD: a
financial contribution per month was granted to 100 individuals with severe
mental illnesses for a 9-month period. Assessments of the subjects were made
before the start of the intervention and after 7 months' duration. A comparison
group including treatment as usual only was followed using the same instruments.
Significant improvements were found for depression and anxiety, social networks,
and sense of self. No differences in functional level were found. Social
initiatives may have treatment and other beneficial effects and should be
integrated into working contextually with persons with severe mental illnesses.
PMID- 26433375
TI - The Potential Roles of Aquaporin 4 in Alzheimer's Disease.
AB - Aquaporin 4 (AQP4) is the major water channel expressed in the central nervous
system (CNS), and it is primarily expressed in astrocytes. It has been studied in
various brain pathological conditions. However, the potential for AQP4 to
influence Alzheimer's disease (AD) is still unclear. Research regarding AQP4
functions related to AD can be traced back several years and has gradually
progressed toward a better understanding of the potential mechanisms. Currently,
it has been suggested that AQP4 influences synaptic plasticity, and AQP4
deficiency may impair learning and memory, in part, through glutamate transporter
1 (GLT-1). AQP4 may mediate the clearance of amyloid beta peptides (Abeta). In
addition, AQP4 may influence potassium (K(+)) and calcium (Ca(2+)) ion transport,
which could play decisive roles in the pathogenesis of AD. Furthermore, AQP4
knockout is involved in neuroinflammation and interferes with AD. To date, no
specific therapeutic agents have been developed to inhibit or enhance AQP4.
However, experimental results strongly emphasize the importance of this topic for
future investigations.
PMID- 26433376
TI - Sulforaphane Ameliorates Okadaic Acid-Induced Memory Impairment in Rats by
Activating the Nrf2/HO-1 Antioxidant Pathway.
AB - Okadaic acid (OKA) causes memory impairment and attenuates nuclear factor
erythroid 2-related factor 2 (Nrf2) along with oxidative stress and
neuroinflammation in rats. Sulforaphane (dietary isothiocyanate compound), an
activator of Nrf2 signaling, exhibits neuroprotective effects. However, the
protective effect of sulforaphane in OKA-induced neurotoxicity remains
uninvestigated. Therefore, in the present study, the role of sulforaphane in OKA
induced memory impairment in rats was explored. A significant increased Nrf2
expression in the hippocampus and cerebral cortex was observed in trained (Morris
water maze) rats, and a significant decreased Nrf2 expression in memory-impaired
(OKA, 200 ng icv) rats indicated its involvement in memory function. Sulforaphane
administration (5 and 10 mg/kg, ip, days 1 and 2) ameliorates OKA-induced memory
impairment in rats. The treatment also restored Nrf2 and its downstream
antioxidant protein expression (GCLC, HO-1) and attenuated oxidative stress (ROS,
nitrite, GSH), neuroinflammation (NF-kappaB, TNF-alpha, IL-10), and neuronal
apoptosis in the cerebral cortex and hippocampus of OKA-treated rats. Further, to
determine whether modulation of Nrf2 signaling is responsible for the protective
effect of sulforaphane, in vitro, Nrf2 siRNA and its downstream HO-1 inhibition
studies were carried out in a rat astrocytoma cell line (C6). The protective
effects of sulforaphane were abolished with Nrf2 siRNA and HO-1 inhibition in
astrocytes. The results suggest that Nrf2-dependent activation of cellular
antioxidant machinery results in sulforaphane-mediated protection against OKA
induced memory impairment in rats. Graphical Abstract ?.
PMID- 26433377
TI - Dopamine Burden Triggers Neurodegeneration via Production and Release of TNF
alpha from Astrocytes in Minimal Hepatic Encephalopathy.
AB - Dopamine (DA)-induced learning and memory impairment is well documented in
minimal hepatic encephalopathy (MHE), but the contribution of DA to
neurodegeneration and the involved underlying mechanisms are not fully
understood. In this study, the effect of DA on neuronal apoptosis was initially
detected. The results showed that MHE/DA (10 MUg)-treated rats displayed neuronal
apoptosis. However, we found that DA (10 MUM) treatment did not induce evident
apoptosis in primary cultured neurons (PCNs) but did produce TNF-alpha in primary
cultured astrocytes (PCAs). Furthermore, co-cultures between PCAs and PCNs
exposed to DA exhibited increased astrocytic TNF-alpha levels and neuronal
apoptosis compared with co-cultures exposed to the vehicle, indicating the
attribution of the neuronal apoptosis to astrocytic TNF-alpha. We also
demonstrated that DA enhanced TNF-alpha production from astrocytes by activation
of the TLR4/MyD88/NF-kappaB pathway, and secreted astrocytic TNF-alpha
potentiated neuronal apoptosis through inactivation of the PI3K/Akt/mTOR pathway.
Overall, the findings from this study suggest that DA stimulates substantial
production and secretion of astrocytic TNF-alpha, consequently and indirectly
triggering progressive neurodegeneration, resulting in cognitive decline and
memory loss in MHE.
PMID- 26433378
TI - Neuroprotective and Functional Improvement Effects of Methylene Blue in Global
Cerebral Ischemia.
AB - Transient global cerebral ischemia (GCI) causes delayed neuronal cell death in
the vulnerable hippocampus CA1 subfield, as well as behavioral deficits. Ischemia
reperfusion (I/R) produces excessive reactive oxygen species and plays a key role
in brain injury. The mitochondrial electron respiratory chain is the main
cellular source of free radical generation, and dysfunction of mitochondria has a
significant impact on the neuronal cell death in ischemic brain. The aim of the
present study is to investigate the potential beneficial effects of methylene
blue (MB) in a four-vessel occlusion (4VO) GCI model on adult male rats. MB was
delivered at a dose of 0.5 mg/kg/day for 7 days, through a mini-pump implanted
subcutaneously after GCI. We first found that MB significantly improved ischemic
neuronal survival in the hippocampal CA1 region as measured by cresyl violet
staining as well as NeuN staining. We also found that MB has the ability to
rescue ischemia-induced decreases of cytochrome c oxidase activity and ATP
generation in the CA1 region following I/R. Further analysis with labeling of
MitoTracker(r) Red revealed that the depolarization of mitochondrial membrane
potential (MMP) was markedly attenuated following MB treatment. In addition, the
induction of caspase-3, caspase-8, and caspase-9 activities and the increased
numbers of TUNEL-positive cells of the CA1 region were significantly reduced by
MB application. Correspondingly, Barnes maze tests showed that the deterioration
of spatial learning and memory performance following GCI was significantly
improved in the MB-treatment group compared to the ischemic control group. In
summary, our study suggests that MB may be a promising therapeutic agent
targeting neuronal cell death and cognitive deficits following transient global
cerebral ischemia.
PMID- 26433379
TI - Help-seeking behaviours, barriers to care and self-efficacy for seeking mental
health care: a population-based study in Rwanda.
AB - PURPOSE: Mental disorders commonly affect young people but usually go
unrecognized and untreated. This study aimed to investigate help-seeking
behaviours, barriers to care and self-efficacy for seeking mental health care
among young adults with current depression and/or suicidality in a low-income
setting. METHODS: This cross-sectional study used two sub-populations: a sub
sample of those suffering from current depression and/or suicidality (n = 247)
and another of those not suffering from these conditions and not suffering from
any other mental condition investigated (n = 502). Help-seeking behaviours,
barriers to care and self-efficacy for mental health care seeking were measured
among those suffering from current depression and/or suicidality (n, %). Logistic
regression was used to identify risk factors for experiencing barriers to care.
Self-efficacy for seeking mental health care was compared between men and women
in the two sub-populations. RESULTS: Of the 247 men and women with current
depression and/or suicidality, 36.0 % sought help at a health care unit and 64.0
% from trusted people in the community. Only six people received help from a
mental health professional. The identified barriers were mainly related to
accessibility and acceptability of health services. For the population suffering
from current depression and/or suicidality, the self-efficacy scale for seeking
mental health care suggested a low confidence in accessing mental health care but
a high confidence in respondents' ability to successfully communicate with health
care staff and to cope with consequences of seeking care. CONCLUSION: The current
study clearly highlights young adults' poor access to mental health care
services. To reach universal health coverage, substantial resources need to be
allocated to mental health, coupled with initiatives to improve mental health
literacy in the general population.
PMID- 26433380
TI - The Antidiabetic Drug Metformin Stimulates Glycolytic Lactate Production in
Cultured Primary Rat Astrocytes.
AB - Metformin is the most frequently used drug for the treatment of type 2 diabetes
in humans. However, only little is known about effects of metformin on brain
metabolism. To investigate potential metabolic consequences of an exposure of
brain cells to metformin, we incubated rat astrocyte-rich primary cultures with
this compound. Metformin in concentrations of up to 30 mM did not acutely
compromise the viability of astrocytes, but caused a time- and concentration
dependent increase in cellular glucose consumption and lactate production. For
acute incubations in the hour range, the presence of 10 mM metformin doubled the
glycolytic flux, while already 1 mM metformin doubled glycolytic flux during
incubation for 24 h. In addition to metformin, also other guanidino compounds
increased astrocytic lactate production. After 4 h of incubation, half-maximal
stimulation of glycolysis was observed for metformin, guanidine and phenformin at
concentrations of around 3 mM, 3 mM and 30 uM, respectively. The acute
stimulation of glycolytic lactate production by metformin was persistent after
removal of extracellular metformin and was also observed, if glucose was absent
from the incubation medium or replaced by other hexoses. The metformin-induced
stimulation of glycolytic flux was not prevented by compound C, an inhibitor of
AMP-dependent protein kinase, nor was it additive to the stimulation of
glycolytic flux caused by respiratory chain inhibitors. These data demonstrate
that the antidiabetic drug metformin has the potential to strongly activate
glycolytic lactate production in brain astrocytes.
PMID- 26433381
TI - Modification of Astrocyte Metabolism as an Approach to the Treatment of Epilepsy:
Triheptanoin and Acetyl-L-Carnitine.
AB - Epilepsy is a severe neurological disorder characterized by altered electrical
activity in the brain. Important pathophysiological mechanisms include disturbed
metabolism and homeostasis of major excitatory and inhibitory neurotransmitters,
glutamate and GABA. Current drug treatments are largely aimed at decreasing
neuronal excitability and thereby preventing the occurrence of seizures. However,
many patients are refractory to treatment and side effects are frequent. Temporal
lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults.
In rodents, the pilocarpine-status epilepticus model reflects the pathology and
chronic spontaneous seizures of TLE and the pentylenetetrazole kindling model
exhibits chronic induced limbic seizures. Accumulating evidence from studies on
TLE points to alterations in astrocytes and neurons as key metabolic changes. The
present review describes interventions which alleviate these disturbances in
astrocyte-neuronal interactions by supporting mitochondrial metabolism. The
compounds discussed are the endogenous transport molecule acetyl-L-carnitine and
the triglyceride of heptanoate, triheptanoin. Both provide acetyl moieties for
oxidation in the tricarboxylic acid cycle whereas heptanoate is also provides
propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in
anaplerosis-the refilling of the tricarboxylic acid cycle.
PMID- 26433382
TI - Improved validation of IDP ensembles by one-bond Calpha-Halpha scalar couplings.
AB - Intrinsically disordered proteins (IDPs) are best described by ensembles of
conformations and a variety of approaches have been developed to determine IDP
ensembles. Because of the large number of conformations, however, cross
validation of the determined ensembles by independent experimental data is
crucial. The (1)JCalphaHalpha coupling constant is particularly suited for cross
validation, because it has a large magnitude and mostly depends on the often less
accessible dihedral angle psi. Here, we reinvestigated the connection between
(1)JCalphaHalpha values and protein backbone dihedral angles. We show that
accurate amino-acid specific random coil values of the (1)JCalphaHalpha coupling
constant, in combination with a reparameterized empirical Karplus-type equation,
allow for reliable cross-validation of molecular ensembles of IDPs.
PMID- 26433383
TI - Identification and activation of novel biosynthetic gene clusters by genome
mining in the kirromycin producer Streptomyces collinus Tu 365.
AB - Streptomycetes are prolific sources of novel biologically active secondary
metabolites with pharmaceutical potential. S. collinus Tu 365 is a Streptomyces
strain, isolated 1972 from Kouroussa (Guinea). It is best known as producer of
the antibiotic kirromycin, an inhibitor of the protein biosynthesis interacting
with elongation factor EF-Tu. Genome Mining revealed 32 gene clusters encoding
the biosynthesis of diverse secondary metabolites in the genome of Streptomyces
collinus Tu 365, indicating an enormous biosynthetic potential of this strain.
The structural diversity of secondary metabolisms predicted for S. collinus Tu
365 includes PKS, NRPS, PKS-NRPS hybrids, a lanthipeptide, terpenes and
siderophores. While some of these gene clusters were found to contain genes
related to known secondary metabolites, which also could be detected in HPLC-MS
analyses, most of the uncharacterized gene clusters are not expressed under
standard laboratory conditions. With this study we aimed to characterize the
genome information of S. collinus Tu 365 to make use of gene clusters, which
previously have not been described for this strain. We were able to connect the
gene clusters of a lanthipeptide, a carotenoid, five terpenoid compounds, an
ectoine, a siderophore and a spore pigment-associated gene cluster to their
respective biosynthesis products.
PMID- 26433384
TI - Microbial conversion of pyrolytic products to biofuels: a novel and sustainable
approach toward second-generation biofuels.
AB - This review highlights the potential of the pyrolysis-based biofuels production,
bio-ethanol in particular, and lipid in general as an alternative and sustainable
solution for the rising environmental concerns and rapidly depleting natural fuel
resources. Levoglucosan (1,6-anhydrous-beta-D-glucopyranose) is the major
anhydrosugar compound resulting from the degradation of cellulose during the fast
pyrolysis process of biomass and thus the most attractive fermentation substrate
in the bio-oil. The challenges for pyrolysis-based biorefineries are the
inefficient detoxification strategies, and the lack of naturally available
efficient and suitable fermentation organisms that could ferment the levoglucosan
directly into bio-ethanol. In case of indirect fermentation, acid hydrolysis is
used to convert levoglucosan into glucose and subsequently to ethanol and lipids
via fermentation biocatalysts, however the presence of fermentation inhibitors
poses a big hurdle to successful fermentation relative to pure glucose. Among the
detoxification strategies studied so far, over-liming, extraction with solvents
like (n-butanol, ethyl acetate), and activated carbon seem very promising, but
still further research is required for the optimization of existing
detoxification strategies as well as developing new ones. In order to make the
pyrolysis-based biofuel production a more efficient as well as cost-effective
process, direct fermentation of pyrolysis oil-associated fermentable sugars,
especially levoglucosan is highlly desirable. This can be achieved either by
expanding the search to identify naturally available direct levoglusoan utilizers
or modify the existing fermentation biocatalysts (yeasts and bacteria) with
direct levoglucosan pathway coupled with tolerance engineering could
significantly improve the overall performance of these microorganisms.
PMID- 26433386
TI - Overexpression of PTP4A3 is associated with metastasis and unfavorable prognosis
in bladder cancer.
AB - PURPOSE: Bladder cancer (BC) is the most common malignancy in urinary system. The
prognosis of metastatic BC is poor, but there remains no reliable marker to early
detect metastasis. Dysregulated prenylated protein tyrosine phosphatases (PTPs)
are commonly associated with cancer metastasis. From a published BC
transcriptome, we identified that PTP IVA3 (PTP4A3) was the most significantly
upregulated gene implicated in tumor progression among genes related to
prenylated PTPs. We therefore analyzed PTP4A3 expression in our well
characterized cohort of BC. METHODS: By immunohistochemistry, PTP4A3 expression
was determined using H-score. PTP4A3 expression of 295 BCs was compared with
clinicopathological parameters, and the effect of PTP4A3 on cancer-specific
survival (CSS) and metastasis-free survival (MFS) was also examined. Two
independent sets of BCs were used to assess PTP4A3 protein and transcript
expression in normal urothelium and different stage tumors. RESULTS: PTP4A3
overexpression was significantly associated with higher pT stage (P < 0.001),
nodal metastasis (P < 0.001), vascular invasion (P < 0.001), and perineural
invasion (P = 0.021). In multivariate analysis, PTP4A3 overexpression was an
independent predictor for CSS (P < 0.001) and MFS (P = 0.007). Notably, the
difference in CSS and MFS between high and low PTP4A3-expressing tumors was also
significant in muscle-invasive BCs. PTP4A3 protein expression showed significant
and stepwise increments from normal urothelium to noninvasive BC, invasive BC,
and metastatic foci (P < 0.001). PTP4A3 transcript was also obviously upregulated
in high-stage BC (P < 0.001). CONCLUSIONS: PTP4A3 may play a role in BC
oncogenesis and is a predictive marker of metastasis. PTP4A3 overexpression
represents an independent prognosticator for BC, suggesting its potential
theranostic value.
PMID- 26433387
TI - Robotic versus conventional laparoscopic pyeloplasty in children less than 20 kg
by weight: single-center experience.
AB - PURPOSE: To compare outcomes of robotic versus conventional laparoscopic
pyeloplasty in children less than 20 kg by weight. METHODS: Nineteen patients
undergoing RP and twenty-five LP under 20 kg by weight were compared
retrospectively with respect to demographics and operative, postoperative, and
follow-up data. For all cases, a lateral transperitoneal approach was used and
all anastomoses were stented. Success was defined as the resolution of
preoperative symptoms and hydronephrosis postoperatively. If either case is not
fulfilled, a renogram was obtained postoperatively. Student's t test was used for
statistical analysis. RESULTS: Forty-four patients underwent forty-seven
pyeloplasties (19 RP and 25 LP), with three patients undergoing bilateral
simultaneous laparoscopic procedure with mean age of 2.7 and 2.4 years in RP and
LP, respectively. The robotic procedures were superior in terms of shorter mean
hospital stay by one and half day on an average. Minimum time taken for RP was 60
min, while for LP it was 90 min. Both procedures were comparable in terms of
complication rate, success rate as well as operating time. CONCLUSIONS: This
comparative study confirms the feasibility, efficacy, and safety of robotic
pyeloplasty in infants and toddlers. The obvious advantage is being shorter
hospital stay. Further prospective studies will be needed to show its superiority
over LP.
PMID- 26433385
TI - David and Goliath: chemical perturbation of eukaryotes by bacteria.
AB - Environmental microbes produce biologically active small molecules that have been
mined extensively as antibiotics and a smaller number of drugs that act on
eukaryotic cells. It is known that there are additional bioactives to be
discovered from this source. While the discovery of new antibiotics is challenged
by the frequent discovery of known compounds, we contend that the eukaryote
active compounds may be less saturated. Indeed, despite there being far fewer
eukaryotic-active natural products these molecules interact with a far richer
diversity of molecular and cellular targets.
PMID- 26433388
TI - Acute and Chronic Management of Neuromyelitis Optica Spectrum Disorder.
AB - OPINION STATEMENT: Neuromyelitis optica and neuromyelitis optica spectrum
disorder (NMO/NMOSD) is a rare but clinically aggressive demyelinating disease of
the central nervous system (CNS) caused by antibodies against water channel
protein aquaporin 4 (AQP4) in the astrocytic foot processes. Patients typically
present with optic neuritis (ON) or longitudinally extensive transverse myelitis
(LETM). The majority of patients with NMOSD show good response to treatment with
steroids and plasmapheresis in the acute setting; however, 90 % of patients will
eventually have clinical relapses and accrue permanent disability. Currently,
immune modulation is the mainstay of maintenance therapy with anti CD-20
(rituximab, RituxanTM) having collectively the strongest evidence to support its
use and mycophenolate mofetil having comparable reductions in absolute relapse
rate (ARR) and expanded disability status scale (EDSS) scores. Azathioprine,
mitoxantrone, and methotrexate also have retrospective case series data that
demonstrate reduction in ARR and stabilization of EDSS but with higher relapse
rates and exposure to greater risk of treatment toxicities. Excitingly, multiple
novel therapies are under clinical study for patients who are refractory to these
first-line therapies including monoclonal antibodies targeting interleukin-6 (IL
6), CD19, CD20, complement, and neutrophil elastase inhibitors which may provide
additional options for patients with severe clinical presentations. Importantly,
no randomized clinical trials have been published to date comparing clinical
outcomes of different maintenance therapies in NMOSD. Several trials are
currently underway, and results will help guide future management decisions as
current evidence is from many small, retrospective case series and cohort studies
with many potential confounds.
PMID- 26433390
TI - How can the health situation and well-being of staff at German schools for the
severely handicapped be improved?
AB - PURPOSE: The aim of the study was to describe measures suggested by staff at
German schools for the severely handicapped regarding possibilities to improve
their health situation and well-being at work. We further wanted to analyze
whether sociodemographic, occupation-related, and health-related characteristics
influence the type of measures proposed. METHODS: The cross-sectional study was
carried out between August 2010 and August 2012 at 13 schools for the handicapped
focusing on motoric and/or holistic development of severely handicapped pupils.
Data of teachers and educational staff were surveyed using written
questionnaires. The analysis is based on free-text answers regarding the
question: "What specific occupation-related measures would lead to an improvement
of your well-being or health situation at the workplace?" RESULTS: A total of 395
persons (response proportion: 59.7 %) with a mean age of 45 years and
predominantly female (86.8 %) participated in our survey. A total of 205 persons
answered the study question providing 456 improvement suggestions, which were
classified into 6 main and 13 subcategories. The main categories were
professional education and supervision, organization of working tasks and time,
work safety and work equipment, social aspects of work, human resources and
contractual framework, and other. Measures proposed were influenced by gender,
burden by nursing activities, teaching, and administrative tasks, and frequency
of deterioration in working atmosphere. DISCUSSION: Proposed measures raise
awareness for job-related health stressors and are a starting point to improve
working conditions at these schools. Since suggestions vary widely by school and
composition of staff, individual priorities have to be set and discussed with the
school management.
PMID- 26433389
TI - Elevated OCT1 participates in colon tumorigenesis and independently predicts poor
prognoses of colorectal cancer patients.
AB - Octamer transcription factor 1 (OCT1) was found to influence the genesis and
progression of numerous cancers except for colorectal cancer (CRC). This study
tried to explore the role of OCT1 in CRC and clarify the association between its
expression and patients' clinical outcome. Transcriptional and post
transcriptional expression of OCT1 was detected in CRC cancerous tissues and
paired normal mucosae by real-time PCR as well as immunohistochemistry. Moreover,
the effect of OCT1 knockdown on CRC cell proliferation was investigated both in
vitro and in vivo using Cell Counting Kit-8 assay, colony-forming assay, and
mouse tumorigenicity assay. Expression of OCT1 was found to be elevated in CRC.
Suppression of OCT1 significantly inhibited CRC cell proliferation both in vitro
and in vivo. Furthermore, upregulated level of OCT1 was significantly associated
with N stage, M stage, and American Joint Committee on Cancer (AJCC) stage (P =
0.027, 0.014, and 0.002, respectively) as well as differential degree (P =
0.022). By using multivariate Cox hazard model, OCT1 was also shown to be a
factor independently predicting overall survival (OS; P = 0.013, hazard ratio =
2.747, 95 % confidence interval 1.125 to 3.715) and disease-free survival (DFS; P
= 0.004, hazard ratio = 2.756, 95 % confidence interval 1.191 to 4.589) for CRC
patients. Our data indicate that OCT1 carries weight in colorectal carcinogenesis
and functions as a novel prognostic indicator and a promising target of anti
cancer therapy for CRC.
PMID- 26433391
TI - Problematic recreational drug use: is there a role for outpatient sexual health
clinics in identifying those not already engaged with treatment services?
AB - Background There is an association between recreational drug use, high-risk
sexual activity and sexually transmissible infections. Studies have shown a
higher prevalence of drug use in those accessing sexual health services; however,
there are minimal data on the proportion with problematic recreational drug use.
We aimed to understand whether sexual health clinics could identify problematic
drug and alcohol use as a novel referral pathway into treatment services.
METHODS: Males attending two sexual health clinics in London completed
questionnaires. Data were collected on demographics; gender of sexual partner;
use of alcohol and recreational drugs; if they felt they had problematic use of
drugs, alcohol or both; and if they had sought help for their problematic use.
RESULTS: In total, 867 males completed the questionnaire; 387 (44.7%) were men
who have sex with men (MSM). MSM had significantly higher lifetime use of any
drug compared with non-MSM (80.6% vs. 62.5%; P<0.0001). Thirty-five (4.7%) self
identified problematic drug or alcohol use, with no difference between MSM and
non-MSM (6.3% vs. 3.5%; P=0.08). Of those with problematic drug or alcohol use,
20 were currently or had been engaged with a treatment service and 15 had never
engaged with treatment services. MSM were more likely to have ever sought help
for drug or alcohol problems compared with non-MSM (P=0.003). CONCLUSIONS: Some
individuals attending sexual health clinics with problematic drug use have not
engaged with treatment services. It is therefore appropriate to develop screening
tools for sexual health clinics to identify these individuals and novel referral
pathways to engage them in treatment services.
PMID- 26433392
TI - Development and Validation of a High Pressure Liquid Chromatography-UV Method for
the Determination of Treosulfan and Its Epoxy Metabolites in Human Plasma and Its
Application in Pharmacokinetic Studies.
AB - Treosulfan (l-threitol-1,4-di-methanesulfonate) is a prodrug of a bifunctional
alkylating agent that is being used increasingly in pediatric bone marrow
transplantation regimens. The activation pathway is a complex reaction, which
consists of two consecutive reactions leading to epoxybutane derivatives which
are responsible for DNA alkylation. A simple, sensitive high performance liquid
chromatography method for the determination of the sum of treosulfan and its
epoxy metabolites by UV detection after derivatization with sodium
diethyldithiocarbamate in human plasma was developed and validated. Plasma
samples containing treosulfan and epoxy metabolites were converted into
thiocarbamate derivative with 10% sodium diethyldithiocarbamate. Dinitrobiphenyl
was used as an internal standard. The analysis was carried out using a reversed
phase C18 column with a mobile phase consisting of methanol-water (65:35, v/v) at
a flow rate of 1 mL/min. The eluent was monitored at 254 nm. The standard
calibration curve was established between 2.5 and 50 ug/mL, with a correlation
coefficient of 0.9987. Intra- and interday precision and accuracy of the method
was <8% and met the analytical criteria. Pharmacokinetic parameters were
determined in six children who received intravenous treosulfan (dose range 12-24
g/m(2)) in combination with fludarabine prior to blood or marrow transplantation.
PMID- 26433393
TI - Glutathione Deficit Affects the Integrity and Function of the Fimbria/Fornix and
Anterior Commissure in Mice: Relevance for Schizophrenia.
AB - BACKGROUND: Structural anomalies of white matter are found in various brain
regions of patients with schizophrenia and bipolar and other psychiatric
disorders, but the causes at the cellular and molecular levels remain unclear.
Oxidative stress and redox dysregulation have been proposed to play a role in the
pathophysiology of several psychiatric conditions, but their anatomical and
functional consequences are poorly understood. The aim of this study was to
investigate white matter throughout the brain in a preclinical model of redox
dysregulation. METHODS: In a mouse model with impaired glutathione synthesis
(Gclm KO), a state-of-the-art multimodal magnetic resonance protocol at high
field (14.1 T) was used to assess longitudinally the white matter structure,
prefrontal neurochemical profile, and ventricular volume. Electrophysiological
recordings in the abnormal white matter tracts identified by diffusion tensor
imaging were performed to characterize the functional consequences of fractional
anisotropy alterations. RESULTS: Structural alterations observed at peri-pubertal
age and adulthood in Gclm KO mice were restricted to the anterior commissure and
fornix-fimbria. Reduced fractional anisotropy in the anterior commissure (-7.5%
+/- 1.9, P<.01) and fornix-fimbria (-4.5% +/- 1.3, P<.05) were accompanied by
reduced conduction velocity in fast-conducting fibers of the posterior limb of
the anterior commissure (-14.3% +/- 5.1, P<.05) and slow-conducting fibers of the
fornix-fimbria (-8.6% +/- 2.6, P<.05). Ventricular enlargement was found at peri
puberty (+25% +/- 8 P<.05) but not in adult Gclm KO mice. CONCLUSIONS:
Glutathione deficit in Gclm KO mice affects ventricular size and the integrity of
the fornix-fimbria and anterior commissure. This suggests that redox
dysregulation could contribute during neurodevelopment to the impaired white
matter and ventricle enlargement observed in schizophrenia and other psychiatric
disorders.
PMID- 26433395
TI - Statistical controversies in clinical research: long-term follow-up of clinical
trials in cancer.
AB - Long-term follow-up is an important unmet need for the full analysis of new
treatments for cancer. Earlier detection of cancer and more effective treatment
have led to many more patients surviving for more than 5 and even 10 years, so
that evaluating late recurrences and side-effects is an increasingly important
issue. This is particularly relevant for oestrogen receptor-positive breast
cancer, where the existence of late recurrences is well documented. However,
survival for other cancers, notably prostate, colorectal and cervix cancer, has
dramatically increased in recent years due to screening and better treatment of
early lesions. Trials of preventive therapies have an even greater need for long
follow-up. Here, we review these issues and suggest ways in which provision for
long-term follow-up can be improved.
PMID- 26433394
TI - Microbial ribonucleases (RNases): production and application potential.
AB - Ribonuclease (RNase) is hydrolytic enzyme that catalyzes the cleavage of
phosphodiester bonds in RNA. RNases play an important role in the metabolism of
cellular RNAs, such as mRNA and rRNA or tRNA maturation. Besides their cellular
roles, RNases possess biological activity, cell stimulating properties,
cytotoxicity and genotoxicity. Cytotoxic effect of particular microbial RNases
was comparable to that of animal derived counterparts. In this respect, microbial
RNases have a therapeutic potential as anti-tumor drugs. The significant
development of DNA vaccines and the progress of gene therapy trials increased the
need for RNases in downstream processes. In addition, RNases are used in
different fields, such as food industry for single cell protein preparations, and
in some molecular biological studies for the synthesis of specific nucleotides,
identifying RNA metabolism and the relationship between protein structure and
function. In some cases, the use of bovine or other animal-derived RNases have
increased the difficulties due to the safety and regulatory issues. Microbial
RNases have promising potential mainly for pharmaceutical purposes as well as
downstream processing. Therefore, an effort has been given to determination of
optimum fermentation conditions to maximize RNase production from different
bacterial and fungal producers. Also immobilization or strain development
experiments have been carried out.
PMID- 26433397
TI - IJGO at the FIGO 2015 Congress.
PMID- 26433396
TI - Outcomes of prevention of mother to child transmission of the human
immunodeficiency virus-1 in rural Kenya--a cohort study.
AB - BACKGROUND: Success in prevention of mother-to-child transmission (PMTCT) raises
the prospect of eliminating pediatric HIV infection. To achieve global
elimination, however, strategies are needed to strengthen PMTCT interventions.
This study aimed to determine PMTCT outcomes and identify challenges facing its
successful implementation in a rural setting in Kenya. METHODS: A retrospective
cohort design was used. Routine demographic and clinical data for infants and
mothers enrolling for PMTCT care at a rural hospital in Kenya were analysed. Cox
and logistic regression were used to determine factors associated with retention
and vertical transmission respectively. RESULTS: Between 2006 and 2012, 1338
infants were enrolled and followed up for PMTCT care with earlier age of
enrollment and improved retention observed over time. Mother to child
transmission of HIV declined from 19.4 % in 2006 to 8.9 % in 2012 (non-parametric
test for trend p = 0.024). From 2009 to 2012, enrolling for care after 6 months
of age, adjusted Odds Ratio [aOR]: 23.3 [95 % confidence interval (CI): 8.3
65.4], presence of malnutrition ([aOR]: 2.3 [95 % CI: 1.1-5.2]) and lack of
maternal use of highly active antiretroviral therapy (HAART) (aOR: 6.5 [95 % CI:
1.4-29.4]) was associated with increased risk of HIV infection. Infant's older
age at enrollment, malnutrition and maternal HAART status, were also associated
with drop out from care. Infants who were not actively followed up were more
likely to drop out from care (adjusted Hazard Ratio: 6.6 [95 % CI: 2.9-14.6]).
DISCUSSION: We report a temporal increase in the proportion of infants enrolling
for PMTCT care before 3 months of age, improved retention in PMTCT and a
significant reduction in the proportion of infants enrolled who became HIV
infected, emphasizing the benefits of PMTCT. CONCLUSION: A simple set of risk
factors at enrollment can identify mother-infant pairs most at risk of infection
or drop out for targeted intervention.
PMID- 26433398
TI - FIGO consensus guidelines on intrapartum fetal monitoring: Introduction.
PMID- 26433399
TI - FIGO consensus guidelines on intrapartum fetal monitoring: Physiology of fetal
oxygenation and the main goals of intrapartum fetal monitoring.
PMID- 26433400
TI - FIGO consensus guidelines on intrapartum fetal monitoring: Intermittent
auscultation.
PMID- 26433401
TI - FIGO consensus guidelines on intrapartum fetal monitoring: Cardiotocography.
PMID- 26433402
TI - FIGO consensus guidelines on intrapartum fetal monitoring: Adjunctive
technologies.
PMID- 26433403
TI - Dermoscopic insight into skin microcirculation--Burn depth assessment.
AB - To investigate the effectiveness of dermoscopic observation of skin
microcirculation, the dermal capillary integrity of burn wounds was evaluated by
dermoscopy according to a proposed algorithm that is designed to distinguish burn
wounds between superficial dermal burns: SDB, and deep dermal burns: DDB. As the
gold standard for comparison, two widely accepted endpoints of primary healing
within 21 days (SDB) or over 21 days after injury (DDB) were used. A number of
dermatologists conducted diagnostic imaging by dermoscopy. Comparison among
polarized noncontact dermoscopy (PNCD), polarized contact dermoscopy (PCD) and
nonpolarized contact dermoscopy (NPD) was also conducted. Images from the three
modalities were evaluated for color, pattern and qualitative differences among
them. The results of dermoscopy measurements according to the proposed algorithm
showed accuracy of 96.7%, sensitivity of 100.0% and specificity of 94.4%.
Dermoscopy measurements were significantly more accurate than clinical assessment
(p<0.05). The recognition of dots increased for NPD, vessels were most clearly
observed under PCD and colours tended to be more distinctly recognized under
polarized light. Dermoscopy is a useful and simple tool to evaluate not only
epidermal and superficial dermal skin components but also the skin
microcirculation.
PMID- 26433404
TI - Paediatric burns with epilepsy or learning disabilities do not have increased
risk of hospitalisation or increased length of hospital stay compared to the
adult burns.
PMID- 26433405
TI - Imaging morphological changes of intraductal papillary mucinous neoplasm of the
pancreas was associated with its malignant transformation but not with
development of pancreatic ductal adenocarcinoma.
AB - BACKGROUND/OBJECTIVE: A considerable number of branch duct intraductal papillary
mucinous neoplasm (BD-IPMN) developed not infrequently pancreatic malignancy,
either as part of IPMN (malignant IPMN) or as concomitant pancreatic ductal
adenocarcinoma (PDAC). To date, imaging morphological changes predicting
occurrence of malignancy in BD-IPMN are not well-investigated. This study aimed
to evaluate the relationships between occurrence of malignancy in BD-IPMN and
imaging morphological changes of the tumors observed during follow-up. METHODS:
515 BD-IPMN patients with mural nodule <10 mm and negative cytology were
included. 19 patients developed malignant IPMN and 8 patients developed
concomitant PDAC during mean follow-up of 4.7 years. The following imaging
morphological features were assessed: cyst/main pancreatic duct (MPD) diameter,
occurrence of additional cyst/mural nodule. RESULTS: Growth rate of cyst/MPD
diameter were significantly larger in patients who developed malignant IPMN
compared to those in patients whose IPMN remained benign (p = 0.013, p = 0.01).
Occurrence of additional cyst/mural nodule were more frequently observed in
patients who developed malignant IPMN (p = 0.009, p = 0.04). In contrast, none of
the factors associated with imaging morphological changes of IPMN were shown to
be significantly different between patients who developed concomitant PDAC and
patients whose IPMN remained benign. Growth rate of MPD diameter and occurrence
of additional cyst were independent factors associated with development of
malignant IPMN (odds ratio 21.5, and 5.62, respectively). CONCLUSIONS: Imaging
morphological changes of IPMN, such as growth rate of MPD diameter and occurrence
of additional cyst, could be indicators for development of malignant IPMN, but
not for development of concomitant PDAC.
PMID- 26433406
TI - Editorial.
PMID- 26433407
TI - A novel approach to improving antibiotic selection in patients reporting
penicillin allergy.
PMID- 26433408
TI - Delayed red meat allergy: clinical ramifications of galactose-alpha-1,3-galactose
sensitization.
PMID- 26433409
TI - Allergen of the Month--Monk's Rhubarb.
PMID- 26433410
TI - Effects of acute heat stress on lipid metabolism of bovine primary adipocytes.
AB - Heat stress (HS) affects numerous physiological processes including nutrient
partitioning and lipid metabolism. Objectives of this study were to evaluate how
acute HS affects lipid metabolism in subcutaneous adipose tissue of dairy cattle.
Adipose tissue biopsies were performed on Holstein cows for bovine primary
adipocyte isolation and cultured at either 42 degrees C (HS) or 37 degrees C
(thermal neutral, TN). Adipocytes were incubated with increasing isoproterenol
(ISO), and with increasing concentrations of insulin in the presence of ISO to
evaluate changes in lipolysis. Incorporation of radioactive acetate into lipids
was measured as an indicator of lipogenesis. Abundance and phosphorylation of
several lipolytic and lipogenic proteins were also measured. Adipocytes exposed
to HS had an elevated maximal response to ISO and were more sensitive to
lipolytic stimulation by ISO compared with cells cultured at TN. Thermal
treatment did not affect the antilipolytic effects of insulin in the presence of
ISO. Lipogenesis measured as acetate incorporation was not altered by HS, but a
temperature by insulin interaction was observed for the regulation of acetyl CoA
carboxylase, such that the presence of insulin resulted in a reduction in
phosphorylation of acetyl CoA carboxylase in adipocytes cultured at TN but not HS
conditions. Results of this study demonstrate that acute HS has a direct effect
on the regulation of lipolysis and the rate-limiting enzyme of lipogenesis in
isolated bovine adipocytes.
PMID- 26433411
TI - Integration of external estimated breeding values and associated reliabilities
using correlations among traits and effects.
AB - Based on a Bayesian view of linear mixed models, several studies showed the
possibilities to integrate estimated breeding values (EBV) and associated
reliabilities (REL) provided by genetic evaluations performed outside a given
evaluation system into this genetic evaluation. Hereafter, the term "internal"
refers to this given genetic evaluation system, and the term "external" refers to
all other genetic evaluations performed outside the internal evaluation system.
Bayesian approaches integrate external information (i.e., external EBV and
associated REL) by altering both the mean and (co)variance of the prior
distributions of the additive genetic effects based on the knowledge of this
external information. Extensions of the Bayesian approaches to multivariate
settings are interesting because external information expressed on other scales,
measurement units, or trait definitions, or associated with different
heritabilities and genetic parameters than the internal traits, could be
integrated into a multivariate genetic evaluation without the need to convert
external information to the internal traits. Therefore, the aim of this study was
to test the integration of external EBV and associated REL, expressed on a 305-d
basis and genetically correlated with a trait of interest, into a multivariate
genetic evaluation using a random regression test-day model for the trait of
interest. The approach we used was a multivariate Bayesian approach. Results
showed that the integration of external information led to a genetic evaluation
for the trait of interest for, at least, animals associated with external
information, as accurate as a bivariate evaluation including all available
phenotypic information. In conclusion, the multivariate Bayesian approaches have
the potential to integrate external information correlated with the internal
phenotypic traits, and potentially to the different random regressions, into a
multivariate genetic evaluation. This allows the use of different scales,
heritabilities, variance components, measurement units, or trait definitions for
external and internal traits. However, one possible issue for implementing
multivariate Bayesian approaches could be the availability or estimation of
genetic correlations between external and internal traits.
PMID- 26433412
TI - Setup of a rapid method to distinguish among dead, alive, and viable but not
cultivable cells of Pseudomonas spp. in mozzarella cheese.
AB - Pseudomonas spp. is the main psychrotrophic genus involved in the spoilage of raw
milk and more in general of dairy products, such as mozzarella cheese. The
members of this bacterial species are able to produce heat-resistant proteolytic
enzymes, determining the casein hydrolysis, and as a consequence, a reduction of
the shelf life and sensory quality of the products. Therefore, the spoilage
activity could be attributed not only to viable, but also to viable but
noncultivable (VBNC) cells. For this reason, the setup of a non-culture-based
method is useful for a rapid detection of cells that are still alive, but no
longer cultivable, such as VBNC cells. Here we propose a method based on DNA or
RNA content (or both) to reveal the presence of dead, alive, and VBNC cells
belonging to the genus Pseudomonas. The obtained results clearly indicate the
limits of the classical plating count overcome by molecular detection of
Pseudomonas spp. through DNA and RNA analysis, enabling us to establish the
presence of different states of the cells.
PMID- 26433413
TI - Regulation of cell number in the mammary gland by controlling the exfoliation
process in milk in ruminants.
AB - Milk yield is partly influenced by the number of mammary epithelial cells (MEC)
in the mammary gland. It is well known that variations in MEC number are due to
cell proliferation and apoptosis. The exfoliation of MEC from the mammary
epithelium into milk is another process that might influence MEC number in the
mammary tissue. The rate of MEC exfoliation can be assessed by measuring the milk
MEC content through light microscopy, flow cytometry analysis, or an immuno
magnetic method for MEC purification. Various experimental models have been used
to affect milk yield and study the rate of MEC exfoliation. Reducing milking
frequency from twice to once daily did not seem to have any effect on MEC loss in
goat and cow milk after 7 d, but increased MEC loss per day in goats when applied
for a longer period. An increase in MEC exfoliation was also observed during
short days as compared with long days, or in response to an endotoxin-induced
mastitis in cows. Other animal models were designed to investigate the endocrine
control of the exfoliation process and its link with milk production. Suppression
of ovarian steroids by ovariectomy resulted in a greater persistency of lactation
and a decrease in MEC exfoliation. Administering prolactin inhibitors during
lactation or at dry-off enhanced MEC exfoliation, whereas exogenous prolactin
during lactation tended to prevent the negative effect of prolactin inhibitors.
These findings suggest that prolactin could regulate MEC exfoliation. In most of
these studies, variations of MEC exfoliation were associated with variations in
milk yield and changes in mammary epithelium integrity. Exfoliation of MEC could
thus influence milk yield by regulating MEC number in mammary tissue.
PMID- 26433414
TI - Effects of whey or maltodextrin addition during production on physical quality of
white cheese powder during storage.
AB - There is an increasing demand for cheese as a food ingredient, especially as a
flavoring agent. One of the most important cheese flavoring agents is cheese
powder. To obtain an intense cheese flavor, ripened cheese is used as a raw
material in cheese powder but this increases production costs. Moreover, use of
natural cheese decreases the physical quality of powder because of its high fat
content. In this study, we evaluated opportunities to use whey or maltodextrin
for improving the physical quality of powders in production of white cheese
powder. We produced cheese powders with 3 different formulations-control (CON),
whey-added (WACP), and maltodextrin-added (MACP)-and determined the effects of
formulation on cheese powder quality. Physical quality parameters such as color,
densities, reconstitution properties, free fat content, particle morphology, and
sensory characteristics were investigated. The different cheese powders were
stored for 12 mo at 20 degrees C and we evaluated the effect of storage on powder
quality. Addition of maltodextrin to cheese powder formulations significantly
improved their physical quality. The densities and reconstitution properties of
cheese powder were increased and free fat content was decreased by use of
maltodextrin. The MACP particles were spherical with a uniform distribution and
larger particle sizes, whereas CON and WACP particles were wrinkled, irregular
shaped with deep surface dents, and variable in size. Although caking was
observed in scanning electron micrographs after 12 mo of storage, it was not
detected by sensory panelists. The color of cheese powders changed very slowly
during storage but browning was detected. The results of this study show that it
is possible to use maltodextrin or whey in production of white cheese powder to
reduce production costs and improve the physical quality of powders.
PMID- 26433415
TI - Single-step genomic model improved reliability and reduced the bias of genomic
predictions in Danish Jersey.
AB - A bias in the trend of genomic estimated breeding values (GEBV) was observed in
the Danish Jersey population where the trend of GEBV was smaller than the
deregressed proofs for individuals in the validation population. This study
attempted to improve the prediction reliability and reduce the bias of predicted
genetic trend in Danish Jersey. The data consisted of 1,238 Danish Jersey bulls
and 611,695 cows. All bulls were genotyped with the 54K chip, and 1,744 cows were
genotyped with either 7K chips (1,157 individuals) or 54K chips (587
individuals). The trait used in the analysis was protein yield. All cows with EBV
were used in a single-step approach. Deregressed proofs were used as the response
variable. Four alternative approaches were compared with genomic best linear
unbiased prediction (GBLUP) model with bulls in the reference data (GBLUPBull):
(1) GBLUP with both bulls and genotyped cows in the reference data; (2) GBLUP
including a year of birth effect; (3) GEBV from a GBLUP model that accounted for
the difference of EBV between dams and maternal grandsires; and (4) using a
single-step approach. The results indicated all 4 alternatives could reduce the
bias of predicted genetic trend and that the single-step approach performed best.
However, not all these approaches improved reliability or reduced inflation of
GEBV. The reliability was 0.30 and regression coefficients of deregressed proofs
on GEBV were 0.69 in the scenario GBLUPBull. When genotyped cows were included in
the reference population, the regression coefficients decreased to 0.59 but the
reliability increased to 0.35. If a year effect was included in the model, the
prediction reliability decreased to 0.29 and the regression coefficient improved
to 0.75. The method in which GEBV were adjusted for the difference between dam
EBV and maternal grandsire EBV led to much lower regression coefficients though
the reliability increased to 0.4. The single-step approach improved both the
reliability, to 0.38 and regression coefficient to 0.78. Therefore, the bias in
genetic trend was reduced. The results suggest that implementing the single-step
approach is an effective way to improve genomic prediction in Danish Jersey
cattle.
PMID- 26433416
TI - Peripartal changes in reticuloruminal pH and temperature in dairy cows differing
in the susceptibility to subacute rumen acidosis.
AB - The present study aimed to investigate changes in the reticuloruminal pH and
temperature dynamics in periparturient dairy cows. Reticuloruminal pH and
temperature measurements were conducted from 7 d before until 8 d after
parturition using indwelling sensors. Nine Simmental and 4 Brown Swiss dairy cows
were fed a close-up total mixed ration (52.5% neutral detergent fiber, 5.68MJ of
net energy for lactation per kg of dry matter) with additional 1kg/cow per d
concentrate mixture (29.5% neutral detergent fiber and 6.25MJ of net energy for
lactation per kg of dry matter), starting from 2 wk before the estimated calving
date. Postpartum, all cows had free access to the same close-up diet and were
gradually fed increasing amounts of a concentrate-rich total mixed ration for
early-lactation cows (32.7% neutral detergent fiber, 7.22MJ of net energy for
lactation per kg of dry matter). Data showed depressed reticuloruminal pH early
postpartum, but only in the group of cows defined as subacute ruminal acidosis
(SARA) susceptible (n=8), which had a higher duration time of pH <5.8 (753+/
82min/d) compared with SARA-tolerant cows (n=5; 15+/-6min/d). Also, compared with
SARA-tolerant cows (112+/-91min/d), the SARA-susceptible group showed longer
(1,049+/-75min/d) duration time of pH <6.0. When compared by breed, mean
reticuloruminal pH tended to be lower in Simmental (6.16+/-0.03) than in Brown
Swiss cows (6.25+/-0.05), but no differences were observed in the duration of pH
<5.8 between breeds. Simmental cows produced more milk (30.4+/-1.2kg/d) compared
with Brown Swiss cows (27.9+/-1.3kg/d). Neither total dry matter intake nor milk
yield were different between SARA-susceptible and SARA-tolerant groups. However,
SARA-tolerant cows consumed greater amounts of the close-up total mixed ration
than their SARA-susceptible counterparts, whereas no difference was observed in
the intake of the early-lactating total mixed ration between the groups.
Reticuloruminal temperature was not affected by breed or SARA susceptibility.
Interestingly, the mean reticuloruminal temperature and the time duration of
temperature >39.5 degrees C abruptly dropped from d 2 to 1 before calving by 0.35
degrees C and 430min/d, respectively. In conclusion, the strong inter-animal
variation in reticuloruminal pH responses suggests the need for more careful
monitoring and differentiated feeding management of cows during the transition
period, whereby the SARA-susceptible cows may require particular attention
regarding feeding management and diet composition. The abrupt decrease in
reticuloruminal temperature the day before parturition may enable this
noninvasive method as a management tool for prediction of parturition time.
PMID- 26433417
TI - Effect of combined long-term starvation and gamma-irradiation on membrane fatty
acids and cell surface hydrophobicity of Salmonella enterica serovar Typhimurium.
AB - This study was carried out to explore the adaptive mechanisms of Salmonella
enterica serovar Typhimurium, in particular the implication of fatty acids (FA)
in the remodeling of membrane lipid composition to overcome the combined effects
of long-term starvation and gamma-irradiation stresses. In addition, cell surface
hydrophobicity was also evaluated. The bacterial strains (control and starved)
were treated with a nonlethal gamma-irradiation dose of 0.5 kGy and sublethal
doses of 1 kGy. Gas chromatography analysis showed that the FA composition of
starved and gamma-irradiated cells was modified. However starvation combined with
gamma-irradiation induced more modifications in the FA composition than gamma
irradiation or starvation alone. Indeed, the unsaturated FA-to-saturated FA ratio
decreased significantly for both strains compared with gamma-irradiated cells, as
main consequence of the cyclic FA formation. Our results showed that starvation,
irradiation, or combined stresses significantly influenced the hydrophobicity,
and this may have affected the virulence state of Salmonella Typhimurium cells.
This study represents one of the few to demonstrate the modifications on
bacterial membrane as a cellular response to survive to the ionizing radiation
combined with long-term starvation stress.
PMID- 26433418
TI - Effect of a second treatment with prostaglandin F2alpha during the Ovsynch
protocol on luteolysis and pregnancy in dairy cows.
AB - The main objective of this study was to evaluate the effect of a second treatment
with prostaglandin F2alpha (PGF) during Ovsynch on regression of the corpus
luteum (CL) and on fertility to the timed artificial insemination. Two
experiments were performed. In both experiments, cows were randomized to receive
(1) no additional treatments with PGF=1 PGF, or (2) a second PGF treatment at 24h
after the first PGF treatment=2 PGF. The first experiment (n=344 synchronized
lactating dairy cows that received artificial insemination at 81+/-3d in milk)
used the Double-Ovsynch protocol for synchronizing ovulation. Blood samples were
collected at the PGF and final GnRH treatments (72 and 16h before timed
artificial insemination) during the breeding Ovsynch protocol, to determine CL
regression in response to the protocol. Treatment with 2 PGF increased CL
regression from 83.0% with 1 PGF to 97.0% with 2 PGF. The effect of 2 PGF on CL
regression was observed in both primiparous and multiparous cows. Cows with lower
(2.0 to 4.8ng/mL) versus greater (4.9 to 12.0ng/mL) circulating progesterone at
the time of PGF had lower percentage of cows with complete CL regression after 1
PGF (66.7 vs. 88.1%) but not after 2 PGF (95.1 vs. 97.6%). Experiment 2 used
2,148 lactating dairy cows on 11 dairy farms in 4 different regions of the United
States. Cows were synchronized with Ovsynch and received timed artificial
insemination at 60+/-3d in milk. Cows that received 2 PGF had a tendency for
increased pregnancies per artificial insemination (P/AI) compared with cows with
1 PGF (36.1 vs. 33.3%). This tendency for improvement in P/AI was observed in
multiparous but not in primiparous cows. Combining data from the 2 experiments
indicated a 9.45% relative increase in P/AI for cows receiving 2 compared with 1
PGF (37.6 vs. 34.4%) with the increase in P/AI observed in multiparous but not in
primiparous cows. Thus, a second PGF treatment in Ovsynch-type protocols can
increase pregnancy success by about 10%, primarily due to enhanced fertility in
multiparous cows.
PMID- 26433419
TI - Including different groups of genotyped females for genomic prediction in a
Nordic Jersey population.
AB - Including genotyped females in a reference population (RP) is an obvious way to
increase the RP in genomic selection, especially for dairy breeds of limited
population size. However, the incorporation of these females must be conducted
cautiously because of the potential preferential treatment of the genotyped cows
and lower reliabilities of phenotypes compared with the proven pseudo-phenotypes
of bulls. Breeding organizations in Denmark, Finland, and Sweden have implemented
a female-genotyping project with the possibility of genotyping entire herds using
the low-density (LD) chip. In the present study, 5 scenarios for building an RP
were investigated in the Nordic Jersey population: (1) bulls only, (2) bulls with
females from the LD project, (3) bulls with females from the LD project plus non
LD project females genotyped before their first calving, (4) bulls with females
from the LD project plus non-LD project females genotyped after their first
calving, and (5) bulls with all genotyped females. The genomically enhanced
breeding value (GEBV) was predicted for 8 traits in the Nordic total merit index
through a genomic BLUP model using deregressed proof (DRP) as the response
variable in all scenarios. In addition, (daughter) yield deviation and raw
phenotypic data were studied as response variables for comparison with the DRP,
using stature as a model trait. The validation population was formed using a cut
off birth year of 2005 based on the genotyped Nordic Jersey bulls with DRP. The
average increment in reliability of the GEBV across the 8 traits investigated was
1.9 to 4.5 percentage points compared with using only bulls in the RP (scenario
1). The addition of all the genotyped females to the RP resulted in the highest
gain in reliability (scenario 5), followed by scenario 3, scenario 2, and
scenario 4. All scenarios led to inflated GEBV because the regression
coefficients are less than 1. However, scenario 2 and scenario 3 led to less bias
of genomic predictions than scenario 5, with regression coefficients showing less
deviation from scenario 1. For the study on stature, the daughter yield
deviation/daughter yield deviation performed slightly better than the DRP as the
response variable in the genomic BLUP (GBLUP) model. Therefore, adding unselected
females in the RP could significantly improve the reliabilities and tended to
reduce the prediction bias compared with adding selectively genotyped females.
Although the DRP has performed robustly so far, the use of raw data is
recommended with a single-step model as an optimal solution for future genomic
evaluations.
PMID- 26433420
TI - Modifications to Ovsynch improve fertility during resynchronization: Evaluation
of presynchronization with gonadotropin-releasing hormone 6 d before initiation
of Ovsynch and addition of a second prostaglandin F2alpha treatment.
AB - Lactating Holstein cows (n=897) were randomly assigned to a 2*2 factorial
arrangement of treatments to compare the main effects of presynchronization with
GnRH 6 d before beginning an Ovsynch protocol (+/-GnRH) and a second PGF2alpha
treatment 24h after the first (1 vs. 2 PGF2alpha) on pregnancies per artificial
insemination (P/AI). This resulted in the following 4 treatments: (1) an Ovsynch
protocol (GPG, control); (2) presynchronization with GnRH followed by an Ovsynch
protocol (GGPG); (3) an Ovsynch protocol with a second PGF2alpha treatment
(GPPG); and (4) presynchronization with GnRH followed by an Ovsynch protocol with
a second PGF2alpha treatment (GGPPG). All cows were submitted for first timed
artificial insemination (TAI) using a Presynch Ovsynch protocol, and cows
detected in estrus after the second PGF2alpha treatment of the Presynch portion
of the protocol were inseminated and removed from the experiment. Nonpregnant
cows were resynchronized using an Ovsynch protocol initiated 32+/-3 d after
artificial insemination. Blood samples were collected at the first GnRH treatment
(G1), at the PGF2alpha treatment (PGF), and at the last GnRH treatment (G2) of
the Ovsynch protocol and were assayed for progesterone (P4) concentrations.
Overall, P/AI tended to be greater for cows receiving a second PGF2alpha
treatment compared with cows not receiving the second PGF2alpha treatment (40 and
37% for GGPPG and GPPG treatments, respectively, vs. 33 and 32% for GGPG and GPG
treatments, respectively). Interestingly, treatment effects on P/AI were detected
only for resynchronized cows receiving second and greater TAI, but not for cows
receiving first TAI. Fewer cows presynchronized with GnRH had low (<0.5ng/mL) P4
at G1 than cows not presynchronized (13 vs. 25%), and P4 was greater at PGF2alpha
for cows presynchronized with GnRH (4.4 vs. 4.0ng/mL). Cows receiving 2 PGF2alpha
treatments had lower P4 at G2 than cows receiving 1 PGF2alpha treatment (0.15 vs.
0.35ng/mL). Differences in P4 at PGF2alpha were detected only for resynchronized
cows and not for cows submitted for first TAI. We conclude that
presynchronization with GnRH 6 d before beginning an Ovsynch protocol tended to
increase P4 at the first GnRH treatment of an Ovsynch protocol, and that a second
PGF2alpha treatment 24h after the first decreased P4 at TAI, thereby increasing
P/AI in cows resynchronized for second and greater TAI.
PMID- 26433421
TI - Effect of ensiling time and exogenous protease addition to whole-plant corn
silage of various hybrids, maturities, and chop lengths on nitrogen fractions and
ruminal in vitro starch digestibility.
AB - The objective of this study was to evaluate the effects of ensiling time and
exogenous protease addition on soluble CP (% of CP), ammonia-N (% of N), and
ruminal in vitro starch digestibility (ivSD) of whole-plant corn silage (WPCS)
from 3 hybrids, 2 maturities, and 2 chop lengths. Samples from 3 nonisogenic
hybrids [brown midrib containing the bm3 gene mutation (BM3), dual-purpose (DP),
or floury-leafy (LFY)] at 2 harvest maturities [2/3 kernel milk line (early) or
7d later (late)] with 2 theoretical lengths of cut settings (0.64 or 1.95cm) on a
forage harvester were collected at harvest, treated with or without exogenous
protease, and ensiled in triplicate in vacuum heat-sealed plastic bags for 0, 30,
60, 120, and 240d. Thus, the experiment consisted of 120 treatments (3 hybrids *
2 maturities * 2 chop lengths * 2 protease treatments * 5 time points) and 360
mini-silos (3 replications per treatment). Vitreousness, measured by dissection
on unfermented kernels on the day of harvest, averaged 66.8, 65.0, and 59.0% for
BM3, DP, and LFY, respectively. A protease * maturity interaction was observed
with protease increasing ivSD in late but not early maturity. Ensiling time *
hybrid interactions were observed for ammonia-N and soluble CP concentrations
with greater values for FLY than other hybrids only after 120d of ensiling.
Ensiling time * hybrid or protease * hybrid interactions were not observed for
ivSD. Measurements of ivSD were greatest for FLY and lowest for BM3. Length of
the ensiling period did not attenuate negative effects of kernel vitreousness or
maturity on ivSD in WPCS. Results suggest that the dosage of exogenous protease
addition used in the present study may reduce but not overcome the negative
effects of maturity on ivSD in WPCS. No interactions between chop length and
ensiling time or exogenous protease addition were observed for ivSD.
PMID- 26433422
TI - Prospective intervention study with a microarray-based, multiplexed, automated
molecular diagnosis instrument (Verigene system) for the rapid diagnosis of
bloodstream infections, and its impact on the clinical outcomes.
AB - The Verigene Gram-positive blood culture test (BC-GP) and the Verigene Gram
negative blood culture test (BC-GN) identify representative Gram-positive
bacteria, Gram-negative bacteria and their antimicrobial resistance by detecting
resistance genes within 3 h. Significant benefits are anticipated due to their
rapidity and accuracy, however, their clinical utility is unproven in clinical
studies. We performed a clinical trial between July 2014 and December 2014 for
hospitalized bacteremia patients. During the intervention period (N = 88),
Verigene BC-GP and BC-GN was used along with conventional microbiological
diagnostic methods, while comparing the clinical data and outcomes with those
during the control period (N = 147) (UMIN registration ID: UMIN000014399). The
median duration between the initiation of blood culture incubation and the
reporting time of the Verigene system results was 21.7 h (IQR 18.2-26.8) and the
results were found in 88% of the cases by the next day after blood cultures were
obtained without discordance. The hospital-onset infection rate was higher in the
control period (24% vs. 44%, p = 0.002), however, no differences were seen in co
morbidities and severity between the control and intervention periods. During the
intervention period, the time of appropriate antimicrobial agents' initiation was
significantly earlier than that in the control period (p = 0.001) and most cases
(90%; 79/88) were treated with antimicrobial agents with in-vitro susceptibility
for causative bacteria the day after the blood culture was obtained. The costs
for antimicrobial agents were lower in the intervention period (3618 yen vs. 8505
yen, p = 0.001). The 30-day mortality was lower in the intervention period (3%
vs. 13%, p = 0.019).
PMID- 26433423
TI - Failed Attempts to Reduce Inappropriate Laboratory Utilization in an Emergency
Department Setting in Cyprus: Lessons Learned.
AB - BACKGROUND: Laboratory test ordering is a significant part of the diagnosis
definition and disease treatment monitoring process. Inappropriate laboratory
test ordering wastes scarce resources, places unnecessary burden on the health
care delivery system, and exposes patients to unnecessary discomfort.
Inappropriate ordering is caused by many factors, such as lack of guidelines,
defensive medicine, thoughtless ordering, and lack of awareness of costs incurred
to the system. OBJECTIVES: The purpose of this study is to assess two successive
measures, which were introduced in a Cyprus emergency department (ED) for the
purpose of synergistically reducing inappropriate laboratory ordering: the
introduction of a copayment fee to reduce nonemergent visits, and the development
of a Web-based protocol defining the tests emergency physicians could order.
METHODS: An autoregressive integrated moving average model for interrupted time
series analysis was constructed. Data include number and type of tests ordered,
along with number of visits for a period of 4 years from an ED in Cyprus.
RESULTS: Copayment fee and introduction of a revised Web-based protocol for a
test ordering form did not reduce the number of ordered tests in the ED unit.
Copayment fee alone resulted in a statistically significant reduction in ED
visits. CONCLUSIONS: The implementation of two consecutive measures resulted in
an increase of ordered tests per patient. Laboratory ordering is a
multidimensional process that is primarily supplier induced, therefore, all
underlying possible causes must be scrutinized by health authorities. These
include lack of guidelines, defensive medicine and thoughtless prescribing. To
attain significant gains, an integrated approach must be implemented.
PMID- 26433424
TI - First-generation Antipsychotics Are Often Prescribed in the Emergency Department
but Are Often Not Administered with Adjunctive Medications.
AB - BACKGROUND: Although first-generation antipsychotics (FGAs) have long been used
in the emergency department (ED) to treat acute agitation, little is known about
how these medications are used in modern clinical practice. In particular, little
work has been published about whether ED clinicians administer FGAs with
adjunctive medications in accordance with expert guidelines or the prescribing
practices of FGAs over time. OBJECTIVES: 1) To provide a comparison of the
frequency with which FGAs are administered with adjunctive benzodiazepines or
anticholinergic medications. 2) To analyze the prescribing trends for FGAs over
time, particularly in the years after the U.S. Food and Drug Administration (FDA)
black-box warning for droperidol. METHODS: This is a structured review of a
retrospective cohort of patients receiving haloperidol or droperidol in two EDs
over a 7-year period. RESULTS: Haloperidol or droperidol was administered on 2833
patient visits during the study period, with haloperidol being administered most
often. Adjunctive medications are administered less than half of the time. The
use of droperidol has remained relatively static, whereas the use of haloperidol
has increased. CONCLUSIONS: First-generation antipsychotics are still widely
utilized in the ED. When administered, these medications are used with adjunctive
medications that may decrease side effects less than half of the time. Droperidol
use has remained unchanged in the years after the FDA black-box warning, whereas
use of haloperidol has continued to rise.
PMID- 26433425
TI - Endocarditis With Fistulization and Rupture of Aortic Root Abscess to the Left
Atrium.
AB - BACKGROUND: Infective endocarditis (IE) is a difficult emergency department (ED)
diagnosis to make. Symptoms are nonspecific and diverse and the classic triad of
fever, anemia, and murmur is rare. Severe IE causes considerable morbidity and
mortality and should be diagnosed early. However, echocardiogram is essential but
not readily available in the ED and can cause diagnostic delay. CASE REPORT: This
case describes severe IE and its unique presentation, diagnostic challenges, and
the use of bedside cardiac ultrasonography. A 28-year-old previously healthy male
presented with intermittent fevers, arthralgias, and myalgias for 2 weeks. He had
twice been evaluated and diagnosed with lumbar back pain. Physical examination
revealed moderate respiratory distress, pale skin with a cyanotic right lower
extremity, and unequal extremity pulses. He became hypotensive and rapidly
deteriorated. Chest x-ray study showed bilateral pulmonary infiltrates with
subsequent imaging demonstrating worsening septic emboli. Bedside ultrasound
revealed mitral and aortic valve vegetations and a presumed diagnosis of IE with
septic embolization was made. Formal echocardiography (ECHO) confirmed IE with an
aortic root abscess with rupture and fistulization into the left atrium. WHY
SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinical criteria for IE include
blood cultures and ECHO, however, these are often not available to an emergency
physician, making IE a diagnostic challenge even in severe cases. The role of
bedside ultrasound for IE continues to evolve and its utility in the diagnosis of
severe IE is distinctly demonstrated in this case.
PMID- 26433426
TI - Thorn Injury Osteomyelitis.
PMID- 26433427
TI - Impact of Clinical Pharmacists on Initiation of Postintubation Analgesia in the
Emergency Department.
AB - BACKGROUND: Pain and anxiety are common in mechanically ventilated patients, and
frequently undertreated in the emergency department (ED) setting. OBJECTIVE: We
sought to compare the rate of initiation of postintubation analgesia in the ED
before and after intervention by pharmacists specialized in emergency medicine.
METHODS: This was a retrospective cohort study of patients who underwent rapid
sequence intubation (RSI) in the ED. The primary endpoint was overall frequency
of analgesia initiation, with subset analysis of RSI during the ED pharmacist
(EDP) duty hours. Secondary endpoints included frequency of sedative or
anxiolytic use without analgesia, time to initiation of postintubation analgesia,
and adverse drug events (ADEs) resulting in analgesia discontinuation. RESULTS:
Forty-one patients were included in each group. The overall rate of
postintubation analgesia increased after pharmacist intervention, from 20% to 49%
(p = 0.005). Analgesia initiation during EDP hours was 50% and 85% in the pre-
and postintervention groups, respectively. In the preintervention group, more
patients received sedation without analgesia (73% vs. 51%; p = 0.04), and a small
percentage (7%) received neither sedation nor analgesia. Time to initiation of
postintubation analgesia decreased from 98 min to 45 min. ADEs were rare: there
were no discontinuations of analgesic therapy in the preintervention group and
one temporary discontinuation because of hypotension in the postintervention
group. CONCLUSION: Analgesic use after RSI in the ED significantly increased
after the implementation of ED pharmacy services. The large proportion of
patients receiving analgesia during the EDP duty hours suggest the increase may
be related to direct pharmacist involvement in postintubation management.
PMID- 26433428
TI - Evaluation of Warfarin Reversal with 4-Factor Prothrombin Complex Concentrate
Compared to 3-Factor Prothrombin Complex Concentrate at a Tertiary Academic
Medical Center.
AB - BACKGROUND: The U.S. Food and Drug Administration recently approved a four-factor
prothrombin complex concentrate (4-PCC) for warfarin reversal. The literature
supporting its use over three-factor prothrombin complex concentrate (3-PCC) is
limited. OBJECTIVE: Our objective was to retrospectively compare the efficacy of
3-PCC to 4-PCC in reversing warfarin in patients who were actively bleeding.
METHODS: We conducted a single-center, retrospective cohort analysis of adult
patients who received 3-PCC or 4-PCC for international normalized ratio (INR)
reversal. Our study excluded patients not actively bleeding and not on warfarin.
The main outcome was the percentage of patients who achieved warfarin reversal
defined as INR <= 1.3 at first INR check post factor administration. We recorded
baseline data including PCC dose, location of bleed, pre- and posttreatment INR,
and time to INR reversal. RESULTS: We included a total of 53 patients.
Intracranial hemorrhage was the most common site of bleeding (26 [74.3%] in 3-PCC
vs. 12 [66.7%] in 4-PCC). The mean dose of 3-PCC was 25.5 units/kg, compared to
27.9 units/kg of 4-PCC. The mean baseline INR was 2.3 in the 3-PCC group and 3 in
the 4-PCC group (p = 0.03), and the first posttreatment INRs were 1.4 and 1.2,
respectively (p < 0.01). Warfarin reversal was achieved in 15 (42.9%) patients
who received 3-PCC and 15 (83.3%) patients who received 4-PCC (p < 0.01). Faster
time to INR reversal was noted in the 4-PCC group vs. the 3-PCC group (3.7 vs. 5
h, p = 0.48). CONCLUSION: A higher percentage of patients achieved warfarin
reversal with 4-PCC compared to 3-PCC treatment. A prospective randomized control
trial is necessary to confirm our results.
PMID- 26433429
TI - Peripheral Intravenous Line Placement and Utilization in an Academic Emergency
Department.
AB - BACKGROUND: Rising health care costs and increased scrutiny concerning spending
have prompted providers and hospitals to identify unnecessary procedures and
waste. Peripheral intravenous line (pIV) placement is one of the most common
medical procedures performed. A recent study reported that 50% of intravenous
lines placed in the emergency department (ED) went unused. If half of all pIVs
placed in EDs systemically go unused, the costs and complications associated with
pIV placement are unacceptably high. OBJECTIVES: Our study aims to ascertain the
frequency of pIV placement and usage in an urban ED. METHODS: This was a
retrospective review of medical records for consecutive patients seen in an
academic ED in June 2014. The following data points were recorded: age, sex,
chief complaint, acuity level on admission, pIV placement both prehospital and in
the ED, and pIV utilization (for fluids, medications, or contrast
administration). RESULTS: There were 509 charts reviewed, with a median patient
age of 40 years. Common chief complaint categories included neurologic, cardiac,
and skin/soft tissue. Triage acuity was varied, with a mean of 3.3. A pIV was
placed in 55% of subjects. Prehospital providers placed 19%. Of all pIVs placed,
72% were used for the administration of medications, 19% for contrast, and 67%
for fluids. Eighty-five percent of pIVs were used; 51% of patients with a pIV
were admitted from the ED. CONCLUSION: In this study's ED, 85% of pIVs were used
prior to discharge. Strategies to lower pIV placement rates should focus on
alternative routes of medication and fluid administration.
PMID- 26433430
TI - Inferior Vena Cava Filter Migration.
PMID- 26433431
TI - Randomized Controlled Noninferiority Trial Comparing Daptomycin to Vancomycin for
the Treatment of Complicated Skin and Skin Structure Infections in an Observation
Unit.
AB - BACKGROUND: Incidence of methicillin-resistant Staphylococcus aureus (MRSA) is
increasing in complicated skin and skin structure infection (cSSSI) presenting to
emergency departments (EDs). Treatment is heterogeneous and can require inpatient
admission to an observation unit (OU). Vancomycin is commonly used in the OU for
treatment, but increasing MRSA resistance to vancomycin suggests the need for
alternatives. Daptomycin is an alternative but it is not known how it compares
with vancomycin. OBJECTIVE: This study tested the hypothesis that daptomycin is
noninferior to vancomycin for the treatment of cSSSI in an OU, using a relative
risk (RR) of 1.3 as the noninferiority limit. METHODS: Subjects admitted to an ED
based OU with a diagnosis of cSSSI were eligible. Consenting subjects were
randomized 1:1 to intravenous (i.v.) vancomycin at 15 mg/kg dosing every 12 h or
i.v. daptomycin at 4 mg/kg once. Subjects were followed until they met objective
criteria for discharge home or hospital admission. Discharged patients were
prescribed 10-14 days of oral cephalexin and trimethoprim-sulfamethoxazole, or
clindamycin if allergic to either of these medications. The primary endpoint was
meeting objective discharge criteria with no change in antibiotic therapy or
return to the ED for the same cellulitis within 30 days of OU discharge. RESULTS:
There were 100 patients enrolled. RR for satisfying the endpoint was 1.07 (95%
confidence interval 0.58-1.98) for daptomycin compared with vancomycin. Hospital
admission rates were 36% and 32% for daptomycin and vancomycin treatment,
respectively. CONCLUSION: Daptomycin was not inferior to vancomycin in the
treatment of cSSSI in an OU.
PMID- 26433432
TI - Fahr's Disease: A Rare Puzzle for an Emergent Neurological Presentation.
PMID- 26433433
TI - A cylindrical traveling wave ultrasonic motor using bonded-type composite beam.
AB - A cylindrical traveling wave ultrasonic motor using bonded-type composite beam is
proposed in this work. In this new design, a new exciting mode for L-B
(longitudinal-bending) hybrid vibrations using bonded-type is adopted, which
requires only two pieces of PZT ceramic plates and a single metal beam. In the
new motor, the traveling wave of a cylinder can be excited by the L-B vibrations
of a bonded-type beam. When two alternating voltages with phase difference are
applied, the longitudinal and bending vibrations of the beam can be generated
synchronously based on the new exciting mode for L-B hybrid vibrations, and the
temporal phase difference of the two vibrations is always 90 degrees . Finite
element method is adopted to realize the modal degeneration in order to confirm
the final structural parameters of the motor, and analyze the motion trajectory
of the driving tip. After the fabrication of a prototype, the vibration
characteristics and mechanical output ability are measured. The maximum no-load
speed and maximum output torque of the prototype are 342 rpm and 6.26 mN m at a
voltage of 100 Vrms.
PMID- 26433434
TI - Targeted gene delivery to the synovial pannus in antigen-induced arthritis by
ultrasound-targeted microbubble destruction in vivo.
AB - The purpose of this study was to optimize an ultrasound-targeted microbubble
destruction (UTMD) technique to improve the in vivo transfection efficiency of
the gene encoding enhanced green fluorescent protein (EGFP) in the synovial
pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles
and plasmids was locally injected into the knee joints of an antigen-induced
arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions
were varied in the experiments. We also tested local articular and intravenous
injections. The rabbits were divided into five groups: (1)
ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid;
(4) plasmid only; (5) untreated controls. EGFP expression was observed by
fluorescent microscope and immunohistochemical staining in the synovial pannus of
each group. The optimal plasmid dosage and ultrasound parameter were determined
based on the results of EGFP expression and the present and absent of tissue
damage under light microscopy. The irradiation procedure was performed to observe
the duration of the EGFP expression in the synovial pannus and other tissues and
organs, as well as the damage to the normal cells. The optimal condition was
determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output
of 2 W/cm(2) and a 20% duty cycle along with 300 MUg of plasmid. Under these
conditions, the synovial pannus showed significant EGFP expression without
significant damage to the surrounding normal tissue. The EGFP expression induced
by the local intra-articular injection was significantly more increased than that
induced by the intravenous injection. The EGFP expression in the synovial pannus
of the ultrasound+microbubbles+plasmid group was significantly higher than that
of the other four groups (P<0.05). The expression peaked on day 5, remained
detectable on day 40 and disappeared on day 60. No EGFP expression was detected
in the other tissues and organs. The UTMD technique can significantly enhance the
in vivo gene transfection efficiency without significant tissue damage in the
synovial pannus of an AIA model. Thus, this could become a safe and effective non
viral gene transfection procedure for arthritis therapy.
PMID- 26433435
TI - Forced vibrations of SC-cut quartz crystal rectangular plates with partial
electrodes by the Lee plate equations.
AB - Lee plate equations for high frequency vibrations of piezoelectric plates have
been established and perfected over decades with the sole objective of obtaining
accurate predictions of frequency and mode shapes to aid the analysis and design
of quartz crystal resonators. The latest improvement includes extra terms related
to derivatives of the flexural displacement to provide much accurate solutions
for vibrations of the thickness-shear mode, which is the functioning mode of
resonators and has much higher frequency than the flexural mode. The improved Lee
plate equations have been used in the analysis of high frequency vibrations of
quartz crystal plates as an essential step for analysis of AT- and SC-cut quartz
crystal resonators after validations with fully electrode quartz crystal
piezoelectric plates. In this study, closed-form solutions of free and forced
vibrations of SC-cut quartz plates with partial electrodes are obtained. A
procedure has been established for the calculation of dispersion relations,
frequency spectra, selected vibration modes, and capacitance ratios of forced
vibrations. The vibration solutions obtained with the first-order Lee plate
equations are proven to be close to solutions from the Mindlin plate equations.
It is now clear that both the Mindlin and Lee plate equations can be used in the
analysis and design of quartz crystal resonators.
PMID- 26433436
TI - Increased working memory related fMRI signal in children following Tick Borne
Encephalitis.
AB - OBJECTIVE: Tick Borne Encephalitis (TBE) is a viral infection in the central
nervous system endemic in Europe and Asia. While pediatric infection may carry a
lower risk for serious neurological sequelae compared to adults, a large
proportion of children experience long term cognitive problems, most markedly
decreased working memory capacity. We explored whether task related functional
magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) could reveal
a biological correlate of status-post TBE in children. METHODS: We examined 11
serologically verified pediatric TBE patients with central nervous system
involvement with 55 healthy controls with working memory tests and MRI. RESULTS:
The TBE patients showed a prominent deficit in working memory capacity and an
increased task related functional MRI signal in working memory related cortical
areas during a spatial working memory task performed without sedation. No
diffusion differences could be found with DTI, in line with the reported paucity
of anatomical abnormalities. CONCLUSION: This study is the first to demonstrate
functional MRI abnormalities in TBE patients that bears similarity to other
patient groups with diffuse neuronal damage.
PMID- 26433437
TI - [Can we decrease cesarean rate at a university hospital treating high risk
pregnancies?].
AB - OBJECTIVE: To determine which clinical practice changes were responsible for a
decrease in cesarean rate from 19.2% in 2003 to 15.5% in 2012 at our university
hospital treating high risk pregnancies, while verifying the absence of any
increase in neonatal morbidity and death. MATERIALS AND METHODS: A descriptive
retrospective study was undertaken at our labour ward including all patients
delivering in 2003 and in 2012. Maternal, obstetrical and neonatal
characteristics of the two populations were compared. Cesarean rates were
analysed following : (1) Robson classification, (2) some maternal and obstetrical
characteristics, and (3) indications for cesarean. RESULTS: Mean age, BMI and
rate of scarred uterus significantly increased in 2012. The two populations
remained comparable in terms of other criteria studied. The main cause
responsible for decrease in cesarean rate was breech presentations (p<0.05).
Furthermore, significantly less cesareans were performed after labour induction
(p=0.04). We also significantly decreased our elective cesarean rate by more than
3% without increasing cesarean sections during labour, showing a rise in
successful vaginal delivery trials. The impact of in utero transfers on the
global rate of cesarean is highly significant since the latter has been divided
by half in 10 years in this population considered to be of high risk for
cesareans. DISCUSSION: These significant decreases reflect our experience in
allowing vaginal deliveries in breech presentations, and also a better selection
of patients for labour induction. Furthermore, it should be noted that increasing
vaginal delivery trials in various obstetrical situations participated in this
decrease. We clearly found that some indications for elective cesarean can be
avoided, such as multiple pregnancies and scarred uterus, thus showing the
importance of restricting the first indication for cesarean. Finally, the
decrease in cesarean rate had no negative effect on neonatal outcome. CONCLUSION:
Decreasing cesarean rate is possible in a university hospital treating high risk
pregnancies. It requires daily obstetrical case by case critical analysis,
allowing wide acceptance of vaginal delivery trials, and continuously evaluating
clinical practices.
PMID- 26433438
TI - Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and
Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I
Mimetic).
AB - BACKGROUND: Insidious cumulative brain injury from motor vehicle-induced whole
body vibration (MV-WBV) has not yet been studied. The objective of the present
study is to validate whether whole-body vibration for long periods causes
cumulative brain injury and impairment of the cerebral function. We also explored
a preventive method for MV-WBV injury. METHODS: A study simulating whole-body
vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N =
8): (1) 2-week normal control; (2) 2-week sham control (in the tube without
vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5
G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in
the present study are similar to the most common driving conditions); (4) 4-week
sham control; (5) 4-week vibration; (6) 4-week vibration with human
apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham
control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the
rats were evaluated by behavioral, physiological, and histological studies of the
brain. RESULTS: Brain injury from vibration is a cumulative process starting with
cerebral vasoconstriction, squeezing of the endothelial cells, increased free
radicals, decreased nitric oxide, insufficient blood supply to the brain, and
repeated reperfusion injury to brain neurons. In the 8-week vibration group,
which indicated chronic brain edema, shrunken neuron numbers increased and whole
neurons atrophied, which strongly correlated with neural functional impairment.
There was no prominent brain neuronal injury in the 4F groups. CONCLUSIONS: The
present study demonstrated cumulative brain injury from MV-WBV and validated the
preventive effects of 4F preconditioning.
PMID- 26433439
TI - Assessment of Left Atrial Appendage Morphology and Function in Patients with Non
valvular Paroxysmal Atrial Fibrillation with Different Rhythms Using Real-Time 3D
Transesophageal Echocardiography.
AB - The aim of this study was to evaluate the morphology and function of the left
atrial appendage (LAA) in different rhythms of paroxysmal atrial fibrillation
(PaAF) patients using real-time 3D transesophageal echocardiography. This study
included 46 patients with PaAF-24 with PaAF with sinus rhythm (PaAF-S) and 22
with PaAF with fibrillation (PaAF-F)-and 23 healthy volunteers. Real-time 3D
transesophageal echocardiography images of the LAA were acquired in all patients.
LAA end-diastolic volume increased in PaAF-S and PaAF-F, whereas LAA end-systolic
volume increased only in PaAF-F. LAA emptying index, end-diastolic volume and end
systolic volume were strongly negatively correlated. LAA emptying index was
positively correlated with percentage changes in LAA area and diameter, as well
as flow velocity. The co-occurrence of spontaneous echo contrast and thrombus
gradually increased in the PaAF-F group, compared with the PaAF-S group. The
morphology and change in function of the LAA in patients with paroxysmal PaAF can
be evaluated with superior feasibility and reproducibility using real-time 3D
transesophageal echocardiography. Morphologic changes in the LAA appeared earlier
than changes in LAA function during the course of PaAF. Spontaneous echo contrast
and thrombus co-occurred more often in PaAF-F than in PaAF-S.
PMID- 26433440
TI - Changing nomenclature for PBC: From 'cirrhosis' to 'cholangitis'.
PMID- 26433442
TI - Studying epilepsy to understand bipolar disorder?
PMID- 26433441
TI - Unilateral or Bilateral Thoracocentesis for Bilateral Pleural Effusion. A
Prospective Study.
AB - INTRODUCTION: In the absence of firm recommendations, we analyzed whether
unilateral thoracic puncture is sufficient for bilateral pleural effusion (PE),
or if the procedure needs to be performed in both sides. MATERIALS AND METHODS:
Prospective study of patients seen consecutively for bilateral PE during a period
of 3 years and 9 months. All patients underwent simultaneous bilateral
thoracocentesis. The standard protocol variables collected in our hospital served
as study parameters. Size of PE, presence of chest pain or fever, or accompanying
lung abnormalities, different attenuation values on chest computed tomography,
presence of loculated pleural fluid, and radiological resolution in a single side
were also evaluated. RESULTS: A total of 36 patients (19 men; mean age 68.5 +/-
16.5 years) were included. The etiology of the effusion was different in each
side in only 2 patients (5.6%). In 6/32 cases (18.8%), the biological analysis of
the pleural fluid (in terms of transudate/exudate) from both sides did not
correspond with the etiological diagnosis of the effusion. Correlation between
biochemical parameters analyzed in the fluid from both sides (Pearson's
correlation coefficient) ranged between 0.74 (LDH) and 0.998 (NT-proBNP). As
different diagnoses in each side were found in only 2 patients, the circumstances
in which bilateral diagnostic thoracocentesis would be necessary could not be
determined. CONCLUSIONS: Simultaneous bilateral thoracocentesis does not appear
to be recommendable. Larger series are needed to establish which factors might
suggest the need for simultaneous puncture of both PE.
PMID- 26433444
TI - Management of Children with Mild, Moderate, and Moderately Severe Sensorineural
Hearing Loss.
AB - Any degree of hearing loss can have a negative impact on child development. The
amount of impact is largely determined by the type, quality, and timeliness of
intervention. Early identification and management of hearing loss is essential
for minimizing the impact of hearing loss and ensuring that children can reach
their cognitive, linguistic, educational, and social potential. Advances in
hearing technology and broadening of candidacy for same, have resulted in
improved outcomes for many children with hearing loss. Through ongoing hearing
monitoring throughout childhood, children with congenital, late-onset, or
progressive losses can receive timely management from interprofessional,
collaborative teams.
PMID- 26433443
TI - Prostate-specific antigen screening and prostate cancer treatment in renal
transplantation candidates: A survey of U.S. transplantation centers.
AB - INTRODUCTION: Renal transplantation candidates are a highly screened population.
There are currently no guidelines or consensus on prostate cancer (CaP) screening
in these patients. In light of the recent United States Preventive Services Task
Force recommendations against prostate-specific antigen (PSA) screening, we
conducted a survey of transplantation surgeons to gain a better understanding of
practice patterns among U.S. centers. MATERIALS AND METHODS: A 14-question
multiple-choice online survey was e-mailed to 195 U.S. renal transplantation
centers. The questionnaire assessed CaP screening and treatment practices. The
survey also evaluated characteristics of the respondent's institution.
Descriptive statistics were used for each of the responses, and associations were
made with program characterization using logistic or linear regression models.
RESULTS: A total of 90 surgeons responded, representing 65 of 195 programs (33%
response rate). Overall, 89% of respondents reported routinely screening for CaP
in renal transplantation candidates and 71% had set guidelines for PSA screening.
The most common age to start PSA screening was 50 years (51%) and 79% of
respondents reported no age limit to stop PSA screening. Definitive treatment of
CaP was required before proceeding to transplantation in 45% of respondents.
Active surveillance was a viable option in 67% of responders. Most respondents
(73%) replied that the waiting time for eligibility after treatment depended on
the CaP stage and risk. CONCLUSIONS: Although most programs have guidelines on
PSA screening in renal transplantation candidates, there is still variation
nationwide in screening and treatment practices. AS is a viable treatment option
in most of the programs. Our results suggest a benefit of a consensus panel to
recommend guidelines in this population.
PMID- 26433445
TI - Vitamins C and E (ascorbate/alpha-tocopherol) provide synergistic neuroprotection
in the jejunum in experimental diabetes.
AB - The present study evaluated the synergistic effects of the association of
ascorbic acid and alpha-tocopherol on myenteric in the jejunum of diabetic rats.
The rats were randomly divided into four equal groups: untreated normoglycemic
(UC), untreated diabetic (UD), ascorbic acid and alpha-tocopherol-treated
normoglycemic (CAE) and ascorbic acid and alpha-tocopherol-treated diabetic
(DAE). The rats from the CAE and DAE group received supplementation with ascorbic
acid (1g/L in water) and alpha-tocopherol (1% in chow). At 210-days-old, the
animals were sacrified and their jejunum was collected and submitted to
immunohistochemistry. Quantitative and/or morphometric analysis were performed.
Supplementation with ascorbic acid and alpha-tocopherol prevented the cell loss
of myenteric neurons expressing HuC/D and TrkA in an equivalent proportion. We
also observed a reduction of the CGRP nerve fiber varicosities and the prevention
of the increased cell body size of submucosal VIP neurons (p<0.05). The
association of ascorbic acid and alpha-tocopherol reduced the deleterious effects
of diabetes promoting protection on the enteric neurons.
PMID- 26433446
TI - Case of osseous dysplasia with an unusual concentric, circular, radiological
appearance.
AB - Osseous dysplasia is an idiopathic process that is characterised by the
replacement of normal bone with fibrous tissue and metaplastic bone. On
radiographic images it may be predominantly radiolucent, predominantly radio
opaque, or mixed. We present a focal osseous dysplastic lesion with an unusual
concentric, circular, radiographic appearance.
PMID- 26433447
TI - Complications and Failures of Office-Based Endoscopic Angiolytic Laser Surgery
Treatment.
AB - OBJECTIVES/HYPOTHESIS: Although office-based laser surgery applications for
benign and premalignant lesions of the larynx are appealing, there are scant data
on their complications and failures. We review office-based angiolytic laser
surgery in patients with benign laryngeal pathology for rates of complication and
failure. STUDY DESIGN: Retrospective chart review. METHODS: Two hundred fifty
five patients who underwent in-office angiolytic laser surgery treatment over 4
years were reviewed. The criteria for complications and failures were based on
postprocedure stroboscopy and clinical findings. RESULTS: The majority of
patients had unilateral disease, which included polyps (46%), leukoplakia (14%),
papilloma (13%), scar (12%), and varix (11%). There were 382 laser treatments, of
which 56% were by pulsed potassium titanyl phosphate laser. Average energy
delivery was lesion specific, with papilloma receiving the most (mean 351 J) and
varices receiving the least (mean 53 J) energy. Most in-office treatments were
tolerated well. Four percent of patients had complications including stiffness,
atrophy, and transient but prolonged hyperemia. Twenty-seven percent of patients
required multiple laser treatments. Multiple treatments were more likely in
papilloma and leukoplakia. CONCLUSIONS: While in-office laser therapy for benign
vocal fold lesions is appealing, repeated treatment due to incomplete resolution
may be needed. Risks of transient and long-term complications are low but real.
Patient selection and standardized laser energy parameters may help in decreasing
complications and need for repeat procedures.
PMID- 26433448
TI - A fragment of the Escherichia coli ClpB heat-shock protein is a micromolar
melanocortin 1 receptor agonist.
AB - The melanocortin system consists of five receptor subtypes (MC1-5R), endogenous
agonists derived from the proopiomelanocortin gene transcript, and the
antagonists agouti and agouti-related protein. The Escherichia coli heat shock
protein ClpB has previously been described as an antigen mimetic to the
endogenous melanocortin agonist alpha-MSH. Herein, we investigated if a fragment
of the ClpB protein could directly signal through the melanocortin receptors. We
synthesized a complementary fragment of the ClpB protein that partially aligned
with alpha-MSH. Pharmacological assessment of this fragment resulted in no
antagonist activity at the MC3R or the MC4R and no agonist activity at the MC4R.
Partial receptor activation was observed for the MC3R and MC5R at 100 MUM
concentrations. This fragment was shown to be a full micromolar MC1R agonist and
may serve as a template for future research into selective MC1R ligands.
PMID- 26433449
TI - Discovery of the oxazabicyclo[3.3.1]nonane derivatives as potent and orally
active GPR119 agonists.
AB - The design and synthesis of two conformationally restricted oxazabicyclo octane
derivatives as GRP119 agonists is described. Derivatives of scaffold C, with syn
configuration, have the best overall profiles with respect to solubility and in
vivo efficacy. Compound 25a was found to have extremely potent agonistic activity
and was orally active in lowering blood glucose levels in a mouse oral glucose
tolerance test at a dose of 0.1 mg/kg.
PMID- 26433450
TI - Anterior spreader flap technique: A new minimally invasive method for stabilising
and widening the nasal valve.
AB - BACKGROUND: The 'anterior spreader flap' is a new minimally invasive technique,
for the treatment of nasal valve insufficiency or stenosis. The aim of this study
was to present our experience with a series of patients with nasal valve
dysfunction corrected by the minimally invasive spreader flap technique.
METHODOLOGY: We performed a retrospective review of our patients with nasal valve
malfunction who underwent the anterior spreader flap between June 2010 and June
2013. The patients had to judge their symptoms of nasal obstruction pre- and 12
months post-operatively by the Nasal Obstruction and Septoplasty Effectiveness
(NOSE) quality-of-life assessment scale. The difference between the pre- and post
operative evaluations of each group and between the groups was calculated, and it
was statistically analysed. RESULTS: Forty-three patients were treated. In seven
patients, the anterior spreader flap was performed as a single procedure (group
F), in 15 patients the anterior spreader flap was combined with a septoplasty and
a turbinoplasty (group FST), in 10 patients with a turbinoplasty (group FT) and
in 11 with a septoplasty (group FS). All patients reported significant post
operative improvement in nasal breathing (p < 0.05). The mean improvement
(diffNOSE) of all patients was 54.2 points. The 'FS' group and the 'FST' group
showed best post-operative results, but there were no significant differences
between the groups (p > 0.8). CONCLUSIONS: The anterior spreader flap is an
effective and safe method for minimally invasive improvement of nasal breathing
in patients with nasal valve dysfunction.
PMID- 26433451
TI - The DOT flap for nasal sidewall reconstruction.
PMID- 26433452
TI - School Breakfast Policy Is Associated with Dietary Intake of Fourth- and Fifth
Grade Students.
AB - BACKGROUND: Breakfast skipping has been associated with obesity. Schools have
adopted breakfast policies to increase breakfast participation. Recently, there
have been concerns that students in schools where breakfast is served in the
classroom may be eating two breakfasts--one at home and one at school--thereby
increasing their risk of excessive energy intake and weight gain. OBJECTIVE: The
study objective was to compare the prevalence of not eating breakfast, eating
breakfast at home or school only, and eating double breakfasts (home and school)
by students in schools with distinct breakfast policies and evaluate the
relationship of breakfast policy to energy intake and diet quality. DESIGN:
Baseline data were collected in 2011-2012 as part of a cluster randomized
controlled trial to evaluate the effectiveness of a school-based intervention to
promote fruit and vegetable intake and physical activity in low-resource
elementary schools in California. PARTICIPANTS/SETTING: Participants were 3,944
fourth and fifth graders from 43 schools, 20 served breakfast in the cafeteria
before school, 17 served breakfast in the classroom at the start of school, and 6
served "second chance" breakfast (in the cafeteria before school and again at
first recess). STATISTICAL ANALYSIS: As part of a secondary data analysis,
differences in school and individual characteristics by school breakfast policy
were assessed by chi(2) test of independence or analysis of variance.
Associations between school breakfast policy and breakfast eating patterns were
assessed. Outcomes included calorie intake at breakfast, total daily calorie
intake, and diet quality as measured by the Healthy Eating Index 2010. Control
variables included student race/ethnicity, grade, and language spoken at home,
and clustering of students by school. RESULTS: Breakfast in the classroom was
associated with fewer students not eating breakfast (P<0.001), but more eating
breakfast at both home and school (P<0.001). Students in the breakfast in the
classroom group did not have higher mean energy intakes from breakfast or higher
daily energy intakes that were higher than other breakfast policy groups. The
breakfast in the classroom group had higher overall diet quality (P=0.01).
CONCLUSIONS: No evidence was found to support discontinuation of breakfast in the
classroom policy on the basis of concerns that children will eat excess calories.
PMID- 26433453
TI - Racial and Ethnic Disparities in Dietary Intake among California Children.
AB - BACKGROUND: The prevalence of childhood obesity among racial and ethnic minority
groups is high. Multiple factors affect the development of childhood obesity,
including dietary practices. OBJECTIVE: To examine the racial and ethnic
differences in reported dietary practices among the largest minority groups of
California children. METHODS: Data from the 2007 and 2009 California Health
Interview Survey were analyzed using multivariate regression with survey weights
to examine how race, ethnicity, sociodemographic characteristics, and child
factors were associated with specific dietary practices. RESULTS: The sample
included 15,902 children aged 2 to 11 years. In multivariate regressions,
substantial differences in fruit juice, fruit, vegetable, sugar-sweetened
beverages, sweets, and fast-food consumption were found among the major racial
and ethnic groups of children. Asians regardless of interview language were more
likely than whites to have low vegetable intake consumption (Asians English
interview odds ratio [OR] 1.20, 95% CI 1.01 to 1.43; Asians non-English-interview
OR 2.09, 95% CI 1.23 to 3.57) and low fruit consumption (Asians English interview
OR 1.69, 95% CI 1.41 to 2.03; Asians non-English interview OR 3.04, 95% CI 2.00
to 4.6). Latinos regardless of interview language were also more likely than
whites to have high fruit juice (Latinos English interview OR 1.54, 95% CI 1.28
to 1.84 and Latinos non-English interview OR 1.29, 95% CI 1.02 to 1.62) and fast
food consumption (Latinos English interview OR 1.74, 95% CI 1.46 to 2.08 and
Latinos non-English interview OR 1.48, 95% CI 1.16 to 1.91); but Latinos were
less likely than whites to consume sweets (Latinos English interview OR 0.81, 95%
CI 0.66 to 0.99 and Latinos non-English interview OR 0.56, 95% CI 1.16 to 1.91).
CONCLUSIONS: Significant racial and ethnic differences exist in the dietary
practices of California children. Increased fruit and vegetable consumption
appears to be associated with parent education but not income. Our findings
suggest that anticipatory guidance and dietary counseling might benefit from
tailoring to specific ethnic groups to potentially address disparities in
overweight and obesity.
PMID- 26433455
TI - Biomechanical implications of excessive endograft protrusion into the aortic arch
after thoracic endovascular repair.
AB - Endografts placed in the aorta for thoracic endovascular aortic repair (TEVAR)
may determine malappositioning to the lesser curvature of the aortic wall, thus
resulting in a devastating complication known as endograft collapse. This
premature device failure commonly occurs in young individuals after TEVAR for
traumatic aortic injuries as a result of applications outside the physical
conditions for which the endograft was designed. In this study, an experimentally
calibrated fluid-structure interaction (FSI) model was developed to assess the
hemodynamic and stress/strain distributions acting on the excessive protrusion
extension (PE) of endografts deployed in four young patients underwent TEVAR.
Endograft infolding was experimentally measured for different hemodynamic
scenarios by perfusion testing and then used to numerically calibrate the
mechanical behavior of endograft PE. Results evinced that the extent of endograft
can severely alter the hemodynamic and structural loads exerted on the endograft
PE. Specifically, PE determined a physiological aortic coarctation into the
aortic arch characterized by a helical flow in the distal descending aorta. High
device displacement and transmural pressure across the stent-graft wall were
found for a PE longer than 21 mm. Finally, marked intramural stress and principal
strain distributions on the protruded segment of the endograft wall may suggest
failure due to material fatigue. These critical parameters may contribute to the
endograft collapse observed clinically and can be used to design new devices more
suitable for young individuals to be treated with an endoprosthesis for TEVAR of
blunt traumatic aortic injuries.
PMID- 26433456
TI - Changeability of tissue's magnetic remanence after galvanic-magnetostimulation in
upper-back pain treatment.
AB - OBJECTIVE: Research was conducted on parametric profiles of healthy subjects and
patients with cervico-brachial pain syndrome resulting from C4/5 and/or C5/6
discopathy, including magnetic remanence of tissues in marker points 1-12 (L+R)
and functional parameters, and their subsequent change after treatment in group
A, using method of push-pull galvanic magnetostimulation (GMT 2.0). DESIGN: GMT
2.0 device, comprised of one air solenoid and three galvanic solenoids in
electrolytic tubs, was designed for push-pull magnetostimulation of the head,
coupled with simultaneous stimulation of the limbs. SETTING: Clinical trial was
conducted in Outpatient Private Clinic "VIS" under the auspices of Silesian
Higher Medical School in Katowice, Poland. PATIENTS: 55 subjects participated in
the study: control group K consisted of 23 healthy individuals, whereas 33
patients in group A were treated using GMT 2.0. INTERVENTION: Only patients in
group A were treated with GMT 2.0 during 40-min sessions over a period of 10
days. MAIN OUTCOME MEASURES: Parametric profile of the patients was defined using
various measurements: electronic SFTR test (C-Th-shoulders), HR, RR, BDI and VAS
tests, magnetic remanence in marker points 1-12 (L+R) and blood parameters: HB,
ER, CREA, BIL, K(+), Na(+), Cl(-) Fe(2+), Ca(2+) and Mg(2+). RESULTS: There was a
significant reduction in pain (VAS), increase in the range of motion (SFTR),
lower depression symptoms (BDI), slower heart rate (HR), lower blood pressure
(RR), greater concentration of Mg(2+), K(+), Ca(2+)ions and reduction in the
concentration of BIL, CREA Fe(2+) after GMT 2.0 treatment in group A. Evaluation
of magnetic remanence in marker points M1-12 (L+R) initially showed higher values
in group K, which after treatment were normalized to values similar to those in
group K. CONCLUSION: GMT 2.0 treatment in group A resulted in normalization of
magnetic remanence, synergically with increased range of motion (SFTR test),
decreased HR and RR parameters, smaller depressive trends (BDI test), as well as
increased ion levels (K(+), Mg(2+), Ca(2+)) and better functional parameters of
kidneys and liver.
PMID- 26433457
TI - iTIS-PseKNC: Identification of Translation Initiation Site in human genes using
pseudo k-tuple nucleotides composition.
AB - Translation is an essential genetic process for understanding the mechanism of
gene expression. Due to the large number of protein sequences generated in the
post-genomic era, conventional methods are unable to identify Translation
Initiation Site (TIS) in human genes timely and accurately. It is thus highly
desirable to develop an automatic and accurate computational model for
identification of TIS. Considerable improvements have been achieved in developing
computational models; however, development of accurate and reliable automated
systems for TIS identification in human genes is still a challenging task. In
this connection, we propose iTIS-PseKNC, a novel protocol for identification of
TIS. Three protein sequence representation methods including dinucleotide
composition, pseudo-dinucleotide composition and Trinucleotide composition have
been used in order to extract numerical descriptors. Support Vector Machine
(SVM), K-nearest neighbor and Probabilistic Neural Network are assessed for their
performance using the constructed descriptors. The proposed model iTIS-PseKNC has
achieved 99.40% accuracy using jackknife test. The experimental results validated
the superior performance of iTIS-PseKNC over the existing methods reported in the
literature. It is highly anticipated that the iTIS-PseKNC predictor will be
useful for basic research studies.
PMID- 26433454
TI - Disruption of IP3R2-mediated Ca2+ signaling pathway in astrocytes ameliorates
neuronal death and brain damage while reducing behavioral deficits after focal
ischemic stroke.
AB - Inositol trisphosphate receptor (IP3R)-mediated intracellular Ca(2+) increase is
the major Ca(2+) signaling pathway in astrocytes in the central nervous system
(CNS). Ca(2+) increases in astrocytes have been found to modulate neuronal
function through gliotransmitter release. We previously demonstrated that
astrocytes exhibit enhanced Ca(2+) signaling in vivo after photothrombosis (PT)
induced ischemia, which is largely due to the activation of G-protein coupled
receptors (GPCRs). The aim of this study is to investigate the role of astrocytic
IP3R-mediated Ca(2+) signaling in neuronal death, brain damage and behavior
outcomes after PT. For this purpose, we conducted experiments using homozygous
type 2 IP3R (IP3R2) knockout (KO) mice. Histological and immunostaining studies
showed that IP3R2 KO mice were indeed deficient in IP3R2 in astrocytes and
exhibited normal brain cytoarchitecture. IP3R2 KO mice also had the same
densities of S100beta+ astrocytes and NeuN+ neurons in the cortices, and
exhibited the same glial fibrillary acidic protein (GFAP) and glial glutamate
transporter (GLT-1) levels in the cortices and hippocampi as compared with wild
type (WT) mice. Two-photon (2-P) imaging showed that IP3R2 KO mice did not
exhibit ATP-induced Ca(2+) waves in vivo in the astrocytic network, which
verified the disruption of IP3R-mediated Ca(2+) signaling in astrocytes of these
mice. When subject to PT, IP3R2 KO mice had smaller infarction than WT mice in
acute and chronic phases of ischemia. IP3R2 KO mice also exhibited less neuronal
apoptosis, reactive astrogliosis, and tissue loss than WT mice. Behavioral tests,
including cylinder, hanging wire, pole and adhesive tests, showed that IP3R2 KO
mice exhibited reduced functional deficits after PT. Collectively, our study
demonstrates that disruption of astrocytic Ca(2+) signaling by deleting IP3R2s
has beneficial effects on neuronal and brain protection and functional deficits
after stroke. These findings reveal a novel non-cell-autonomous neuronal and
brain protective function of astrocytes in ischemic stroke, whereby suggest that
the astrocytic IP3R2-mediated Ca(2+) signaling pathway might be a promising
target for stroke therapy.
PMID- 26433458
TI - Binary combination of epsilon-poly-L-lysine and isoeugenol affect progression of
spoilage microbiota in fresh turkey meat, and delay onset of spoilage in
Pseudomonas putida challenged meat.
AB - Proliferation of microbial population on fresh poultry meat over time elicits
spoilage when reaching unacceptable levels, during which process slime
production, microorganism colony formation, negative organoleptic impact and meat
structure change are observed. Spoilage organisms in raw meat, especially Gram
negative bacteria can be difficult to combat due to their cell wall composition.
In this study, the natural antimicrobial agents epsilon-poly-L-lysine (epsilon
PL) and isoeugenol were tested individually and in combinations for their
activities against a selection of Gram-negative strains in vitro. All
combinations resulted in additive interactions between epsilon-PL and isoeugenol
towards the bacteria tested. The killing efficiency of different ratios of the
two antimicrobial agents was further evaluated in vitro against Pseudomonas
putida. Subsequently, the most efficient ratio was applied to a raw turkey meat
model system which was incubated for 96 h at spoilage temperature. Half of the
samples were challenged with P. putida, and the bacterial load and microbial
community composition was followed over time. CFU counts revealed that the
antimicrobial blend was able to lower the amount of viable Pseudomonas spp. by
one log compared to untreated samples of challenged turkey meat, while the single
compounds had no effect on the population. However, the compounds had no effect
on Pseudomonas spp. CFU in unchallenged meat. Next-generation sequencing offered
culture-independent insight into population diversity and changes in microbial
composition of the meat during spoilage and in response to antimicrobial
treatment. Spoilage of unchallenged turkey meat resulted in decreasing species
diversity over time, regardless of whether the samples received antimicrobial
treatment. The microbiota composition of untreated unchallenged meat progressed
from a Pseudomonas spp. to a Pseudomonas spp., Photobacterium spp., and
Brochothrix thermosphacta dominated food matrix on the expense of low abundance
species. We observed a similar shift among the dominant species in meat treated
with epsilon-PL or the antimicrobial blend, but the samples differed markedly in
the composition of less abundant species. In contrast, the overall species
diversity was constant during incubation of turkey meat challenged with P. putida
although the microbiota composition did change over time. Untreated or epsilon-PL
treated samples progressed from a Pseudomonas spp. to a Pseudomonas spp. and
Enterobacteriaceae dominated food matrix, while treatment with the antimicrobial
blend resulted in increased relative abundance of Hafnia spp., Enterococcaceae,
and Photobacterium spp. We conclude that the blend delayed the onset of spoilage
of challenged meat, and that all antimicrobial treatments of unchallenged or
challenged meat affect the progression of the microbial community composition.
Our study confirms that the antimicrobial effects observed in vitro can be
extrapolated to a food matrix such as turkey meat. However, it also underlines
the consequence of species-to-species variation in susceptibility to
antimicrobials, namely that the microbial community change while the CFU remains
the same. Addition of antimicrobials may thus prevent the growth of some
microorganisms, allowing others to proliferate in their place.
PMID- 26433459
TI - Assessment of the effect of a Salmonella enterica ser. Typhimurium culture
supernatant on the single-cell lag time of foodborne pathogens.
AB - The objective of this study was the in vitro evaluation of the effect of a cell
free microbial supernatant, produced by a luxS-positive Salmonella enterica ser.
Typhimurium strain, on the single-cell growth kinetic behavior of two strains of
S. enterica (serotypes Enteritidis and Typhimurium) and a methicillin-resistant
Staphylococcus aureus strain. The single-cell lag time (lambda) of the pathogens
was estimated in the absence and presence (20% v/v) of microbial supernatant
based on optical density measurements. As demonstrated by the obtained results,
the tested microbial supernatant had a strain-specific effect on the single-cell
lambda and its variability. Although the mean lambda values were similar in the
absence and presence of microbial supernatant in the case of Salmonella
Enteritidis, a significant (P <= 0.05) reduction and increase in the mean value
of this parameter in the presence of microbial supernatant were observed for
Salmonella Typhimurium and St. aureus, respectively. With regard to the effect of
the tested microbial supernatant on the single-cell variability of lambda,
similar lambda distributions were obtained in its absence and presence for S.
Enteritidis, while considerable differences were noted for the other two tested
organisms; the coefficient of variation of lambda in the absence and presence of
microbial supernatant was 41.6 and 69.8% for S. Typhimurium, respectively, with
the corresponding values for St. aureus being 74.0 and 56.9%. As demonstrated by
the results of bioassays, the tested microbial supernatant exhibited autoinducer
2 activity, indicating a potential association of such quorum sensing compounds
with the observed effects. Although preliminary in nature, the collected data
provide a good basis for future research on the role of quorum sensing in the
single-cell growth behavior of foodborne pathogens.
PMID- 26433460
TI - Detection of hepatitis E virus RNA in raw sausages and liver sausages from retail
in Germany using an optimized method.
AB - Hepatitis E virus (HEV) is a pathogen of increasing importance, which can be
zoonotically transmitted from domestic pigs, wild boar, and deer to humans.
Foodborne transmission by consumption of raw and undercooked liver, meat, or
sausages prepared from infected animals has been documented. The aim of this
study was to investigate the distribution of HEV in different types of sausages
sold in Germany. As no standardized methods for HEV detection in food exist,
several techniques of sample homogenization, virus concentration and nucleic acid
extraction followed by real-time RT-PCR were compared using artificially
contaminated sausages. A method using TRI Reagent(r) Solution showed the best
efficacy of matrix disruption and a treatment with chloroform followed by a
silica-based RNA extraction method resulted in the highest HEV detection rates.
The detection limit of the method was 2.9 * 10(3) and 5.3 * 10(4) genome
equivalents per 5 g raw sausage and 2 g liver sausage, respectively. Application
of the method to raw and liver sausages from retail in Germany resulted in the
HEV genome detection in 14 out of 70 (20%) raw sausages and in 11 out of 50 (22%)
liver sausages. The detected HEV sequences showed a high diversity and belonged
to different subtypes of HEV genotype 3. The results indicate a broad
distribution of HEV-RNA in meat products sold in Germany; however, the
infectivity of the detected virus remains to be assessed in future.
PMID- 26433461
TI - Improvement of the antifungal activity of Litsea cubeba vapor by using a helium
neon (He-Ne) laser against Aspergillus flavus on brown rice snack bars.
AB - The aim of this study was to improve the antifungal activity of the volatile
Litsea cubeba essential oil and its main components (citral and limonene) on
brown rice snack bars by applying He-Ne laser treatment. Different volumes (50
200 MUL) of L. cubeba, citral or limonene were absorbed into a filter paper and
placed inside an oven (18 L). Ten brown rice snack bars (2 cm wide * 4 cm long *
0.5 cm deep) were put in an oven and heated at 180 degrees C for 20 min. The
shelf-life of the treated snack bars at 30 degrees C was assessed and sensory
testing was carried out to investigate their consumer acceptability. A count of
total phenolic content (TPC) and Fourier transform infrared spectroscopy (FTIR)
on the properties of essential oil, citral, and limonene before and after the
laser treatment was studied for possible modes of action. It was found that the
laser treatment improved the antifungal activity of the examined volatile L.
cubeba and citral with Aspergillus flavus inhibition by 80% in comparison with
those of the control not treated with the laser. L. cubeba vapor at 100 MUL with
the laser treatment was found to completely inhibit the growth of natural molds
on the snack bars for at least 25 days; however, without essential oil vapor and
laser treatment, naturally contaminating mold was observed in 3 days. Results
from the sensory tests showed that the panelists were unable to detect flavor and
aroma differences between essential oil treatment and the control. Laser
treatment caused an increase in TPC of citral oil whereas the TPC in limonene
showed a decrease after the laser treatment. These situations could result from
the changing peak of the aliphatic hydrocarbons that was revealed by the FTIR
spectra.
PMID- 26433462
TI - Metabolites and hormones are involved in the intraspecific variability of drought
hardening in radiata pine.
AB - Studies of metabolic and physiological bases of plant tolerance and hardening
against drought are essential to improve genetic breeding programs, especially in
productive species such as Pinus radiata. The exposure to different drought
cycles is a highly effective tool that improves plant conditioning, but limited
information is available about the mechanisms that modulate this process. To
clarify this issue, six P. radiata breeds with well-known differences in drought
tolerance were analyzed after two consecutive drought cycles. Survival rate,
concentration of several metabolites such as free soluble amino acids and
polyamines, and main plant hormones varied between them after drought hardening,
while relative growth ratio and water potential at both predawn and dawn did not.
Hardening induced a strong increase in total soluble amino acids in all breeds,
accumulating mainly those implicated in the glutamate metabolism (GM), especially
L-proline, in the most tolerant breeds. Other amino acids from GM such as gamma
aminobutyric acid (GABA) and L-arginine (Arg) were also strongly increased. GABA
pathway could improve the response against drought, whereas Arg acts as precursor
for the synthesis of spermidine. This polyamine showed a positive relationship
with the survival capacity, probably due to its role as antioxidant under stress
conditions. Finally, drought hardening also induced changes in phytohormone
content, showing each breed a different profile. Although all of them accumulated
indole-3-acetic acid and jasmonic acid and reduced zeatin content in needles,
significant differences were observed regarding abscisic acid, salicylic acid and
mainly zeatin riboside. These results confirm that hardening is not only species
dependent but also an intraspecific processes controlled through metabolite
changes.
PMID- 26433464
TI - SCA38 is rare in Mainland China.
AB - Spinocerebellar ataxias (SCAs) are a group of dominantly inherited
neurodegenerative disorders distributed worldwide. Nearly 35 SCAs have been
localized and 28 genes have been identified. Recently, mutations in the
elongation of a very long chain fatty acids-5 gene (ELOVL5) were reported to
cause a SCA38 subtype. To describe the epidemiology of SCA38 in Mainland China,
we analyzed the coding sequence of ELOVL5 in 346 patients diagnosed as SCAs.
Finally, we did not observe any disease-related gene mutations in ELOVL5. This
suggests that the SCA38 subtype is very rare in Mainland China.
PMID- 26433465
TI - Etiology, clinical characteristics and prognosis of spontaneous intracerebral
hemorrhage in children: A prospective cohort study in China.
AB - BACKGROUND AND OBJECTIVE: Much is known about spontaneous intracerebral
hemorrhage (SICH) in adults, but few studies have examined pediatric SICH,
especially in China. The aim of the present study was to describe the etiology,
clinical characteristics and prognosis of SICH in children from southwest China.
METHOD: Consecutive patients aged 1-18 years with SICH at our medical center were
prospectively enrolled from January 2012 to June 2014. SICH was defined by WHO
criteria and confirmed by CT or MRI findings. Demographic and clinical
information was collected at baseline, and follow-up assessments were conducted
at 3 and 6 months after SICH, when patients were scored on the modified Rankin
Scale (mRS) and events of deaths and recurrent hemorrhagic stroke were recorded.
RESULTS: Among the 70 children (43 males; median age, 12.0 years) in the final
analysis, 44 patients (62.9%) had SICH due to arteriovenous malformation, and
less frequent etiologies were cavernous malformation (n=4), aneurysm (n=2),
tumors (n=2), moyamoya (n=2), hemophilia (n=1), hypertension (n=1), while 14
(20.0%) had SICH of unknown etiology. The mortality rate at 3 months and 6 months
was equal, which was both 3%. The rate of disability was 12.1% at 3 months and
9.1% at 6 months. CONCLUSION: The most frequent etiology of pediatric SICH in
this Chinese cohort was arteriovenous malformation. SICH of unknown etiology
occurred much more often in our cohort than in previously published Caucasian
patients in the US and Europe.
PMID- 26433466
TI - Group cognitive behavioural therapy for insomnia: Effects on sleep and depressive
symptomatology in a sample with comorbidity.
AB - AIM: To investigate the effects of group CBT for insomnia (CBT-I) on insomnia and
depressive symptomatology in a comorbid sample through a randomised controlled
trial with a 6 month follow-up. METHODS: 64 participants were recruited through
advertisements and randomised to receive CBT-I or an active control (relaxation
training: RT) during four group sessions. Insomnia Severity Index and BDI-II were
the primary outcome measures, assessed pre-treatment, post-treatment and at 6
month follow-up. Insomnia and depressive diagnoses, and functional impairment
were assessed before and after treatment, whereas sleep diary data was gathered
continuously from one week before treatment until after treatment. RESULTS: CBT-I
was more efficient than RT in reducing insomnia severity and equally effective in
reducing depressive symptoms, although CBT-I was associated with a higher
proportion of remitted persons than RT, regarding both insomnia and depression
diagnoses. Also, CBT-I was associated with less functional impairment, shorter
sleep onset latency and wake after sleep onset but both treatments had equal
improvements of sleep quality, early morning awakenings and total sleep time.
CONCLUSION: Group CBT-I is an efficient form of insomnia-treatment for people
with insomnia comorbid with depressive symptomatology. The mixed results
regarding depression outcomes warrants replication and further studies into
treatment mechanisms.
PMID- 26433463
TI - Eliminating roles for T-bet and IL-2 but revealing superior activation and
proliferation as mechanisms underpinning dominance of regulatory T cells in
tumors.
AB - Foxp3(+) regulatory T cells (Tregs) are often highly enriched within the tumor
infiltrating T cell pool. Using a well-characterised model of carcinogen-induced
fibrosarcomas we show that the enriched tumor-infiltrating Treg population
comprises largely of CXCR3(+) T-bet(+) 'TH1-like' Tregs which are thymus-derived
Helios(+) cells. Whilst IL-2 maintains homeostatic ratios of Tregs in lymphoid
organs, we found that the perturbation in Treg frequencies in tumors is IL-2
independent. Moreover, we show that the TH1 phenotype of tumor-infiltrating Tregs
is dispensable for their ability to influence tumor progression. We did however
find that unlike Tconvs, the majority of intra-tumoral Tregs express the
activation markers CD69, CD25, ICOS, CD103 and CTLA4 and are significantly more
proliferative than Tconvs. Moreover, we have found that CD69(+) Tregs are more
suppressive than their CD69- counterparts. Collectively, these data indicate
superior activation of Tregs in the tumor microenvironment, promoting their
suppressive ability and selective proliferation at this site.
PMID- 26433467
TI - Unintended pregnancy among HIV-positive pregnant women in Enugu, southeast
Nigeria.
AB - OBJECTIVE: To determine the prevalence and factors associated with unintended
pregnancy among HIV-positive pregnant women in Enugu, southeast Nigeria. METHODS:
A questionnaire-based cross-sectional study was performed of HIV-positive
pregnant women receiving prenatal care at two tertiary health institutions in
Enugu between March 1 and August 31, 2012. The women were interviewed with a
pretested questionnaire. RESULTS: Overall, 180 HIV-positive pregnant women were
recruited, 67 (37.2%) of whom declared that their pregnancy was unintended.
Overall, 174 (96.7%) patients were receiving antiretroviral therapy and 99
(55.0%) had future fertility intensions. Participants with regular partners
(married or cohabiting) had a significantly higher rate of unintended pregnancy
than those with unstable partners (40.3%, n=64/159 vs 14.3%, n=3/21 P=0.029).
Age, parity, educational level, and current treatment with antiretroviral therapy
did not significantly affect the prevalence of unintended pregnancy. CONCLUSION:
A substantial number of HIV-positive pregnant women declared their pregnancies to
be unintended. Modern contraceptives should be made readily available and
accessible to HIV-positive women to help eliminate mother-to-child transmission
of HIV and subsequent new pediatric HIV infections.
PMID- 26433468
TI - Association between sonographic measurement of fetal head circumference and labor
outcome.
AB - OBJECTIVE: To evaluate the association between sonographically measured head
circumference (HC) and labor outcome. METHODS: In a retrospective study at a
tertiary medical center in Israel, data were reviewed for all term singleton
deliveries between July 2007 and December 2012 with HC measurements up to 7days
before delivery. HC was compared between women with operative vaginal delivery
(OVD) or cesarean delivery for prolonged second stage and those with normal
vaginal delivery. The impact of HC above the 75th percentile on pregnancy outcome
was analyzed. RESULTS: The study included 2351 women, of whom 2045 (87.0%) had a
normal vaginal delivery, 259 (11.0%) underwent OVD, and 47 (2.0%) cesarean. Each
10mm increase in HC was associated with increased risk for obstetric intervention
because of a prolonged second stage (adjusted odds ratio [aOR] 1.26; 95%
confidence interval [CI] 1.08-1.46). HC above the 75th percentile was
independently associated with increased odds of OVD (aOR 1.77; 95% CI 1.30-2.41),
1-minute Apgar score less than 7 (aOR 2.91; 95% CI 1.50-5.66), and neonatal
asphyxia (aOR 2.19; 95% CI 1.02-4.71). CONCLUSION: Term HC above the 75th
percentile was associated with increased rates of obstetric interventions because
of a prolonged second stage and might be associated with neonatal asphyxia.
PMID- 26433469
TI - International Federation of Gynecology and Obstetrics opinion on reproductive
health impacts of exposure to toxic environmental chemicals.
AB - Exposure to toxic environmental chemicals during pregnancy and breastfeeding is
ubiquitous and is a threat to healthy human reproduction. There are tens of
thousands of chemicals in global commerce, and even small exposures to toxic
chemicals during pregnancy can trigger adverse health consequences. Exposure to
toxic environmental chemicals and related health outcomes are inequitably
distributed within and between countries; universally, the consequences of
exposure are disproportionately borne by people with low incomes. Discrimination,
other social factors, economic factors, and occupation impact risk of exposure
and harm. Documented links between prenatal exposure to environmental chemicals
and adverse health outcomes span the life course and include impacts on fertility
and pregnancy, neurodevelopment, and cancer. The global health and economic
burden related to toxic environmental chemicals is in excess of millions of
deaths and billions of dollars every year. On the basis of accumulating robust
evidence of exposures and adverse health impacts related to toxic environmental
chemicals, the International Federation of Gynecology and Obstetrics (FIGO) joins
other leading reproductive health professional societies in calling for timely
action to prevent harm. FIGO recommends that reproductive and other health
professionals advocate for policies to prevent exposure to toxic environmental
chemicals, work to ensure a healthy food system for all, make environmental
health part of health care, and champion environmental justice.
PMID- 26433470
TI - Altered purinergic receptor-Ca2+ signaling associated with hypoxia-induced
epithelial-mesenchymal transition in breast cancer cells.
AB - Hypoxia is a feature of the microenvironment of many cancers and can trigger
epithelial-mesenchymal transition (EMT), a process by which cells acquire a more
invasive phenotype with enriched survival. A remodeling of adenosine 5'
triphosphate (ATP)-induced Ca(2+) signaling via purinergic receptors is
associated with epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast
cancer cells. Here, we assessed ATP-mediated Ca(2+) signaling in a model of
hypoxia-induced EMT in MDA-MB-468 cells. Like EGF, hypoxia treatment (1% O2) was
also associated with a significant reduction in the sensitivity of MDA-MB-468
cells to ATP (EC50 of 0.5 MUM for normoxic cells versus EC50 of 5.8 MUM for
hypoxic cells). Assessment of mRNA levels of a panel of P2X and P2Y purinergic
receptors following hypoxia revealed a change in levels of a suite of purinergic
receptors. P2X4, P2X5, P2X7, P2Y1 and P2Y11 mRNAs decreased with hypoxia, whereas
P2Y6 mRNA increased. Up-regulation of P2Y6 was a common feature of both growth
factor- and hypoxia-induced models of EMT. P2Y6 levels were also significantly
increased in basal-like breast tumors compared to other subtypes and breast
cancer patients with higher P2Y6 levels showed reduced overall survival rates.
P2Y6 siRNA-mediated silencing and the P2Y6 pharmacological inhibitor MRS2578
reduced hypoxia-induced vimentin protein expression in MDA-MB-468 cells. P2Y6
inhibition also reduced the migration of mesenchymal-like MDA-MB-231 breast
cancer cells. The up-regulation of P2Y6 appears to be a common feature of the
mesenchymal phenotype of breast cancer cells and inhibition of this receptor may
represent a novel therapeutic target in breast cancer metastasis.
PMID- 26433472
TI - Neural dynamics of object noun, action verb and action noun production in picture
naming.
AB - The verb/noun dissociation has often involved the semantic/grammatical confound.
We conducted two event-related potentials (ERPs) studies with the aim of
minimizing this confound. In Experiment 1 participants named pictures depicting
actions, with verbs or nouns and pictures depicting objects with nouns. In
Experiment 2, participants named objects (nouns) or actions (verbs/nouns) from
the same set of action pictures. Compatible with lexical-semantic processes,
semantic category modulated waveform amplitudes and topographic patterns between
250 and 380 ms after picture-onset in Experiment 1. No such effects were observed
in Experiment 2. No effects were found for grammatical class in both experiments
suggesting that grammatical information is not mandatorily activated during
lexical-semantic processes. Given the absence of dissociation when same pictures
were used the results are described as feed-forward effects from visual to
semantic processing, indicating differential neural networks for lexical
selection of action and object words from their corresponding visual referents.
PMID- 26433471
TI - Interleukin-33 predicts poor prognosis and promotes ovarian cancer cell growth
and metastasis through regulating ERK and JNK signaling pathways.
AB - Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, it
remains a huge challenge to understand the cellular and molecular mechanisms of
the aggressive behavior of EOC cells. Here we investigated the role of an
immunomodulatory cytokine IL-33 and its receptor ST2 in mediating the growth and
metastasis of EOC. Our data show that both IL-33 and ST2 were highly up-regulated
in EOC tumors compared with normal ovary and ovarian benign tumors, and the
expression levels were further increased in tumor tissues at the metastatic site.
The expression levels of IL-33 and ST2 were positively correlated with the Ki-67
expression, and negatively correlated with the patient survival time. Using EOC
cell lines, we observed that cells knocked down of IL-33 gene by siRNA had
reduced migratory and invasive potential, while full length human IL-33 (fl-hIL
33) promoted the invasive, migratory and proliferative capacity of EOC cells and
this process could be inhibited by IL-33 decoy receptor sST2. Signaling pathway
analysis suggested that IL-33 increased the phosphorylation of ERK and JNK which
was blocked by sST2. Fl-hIL-33-induced increases in EOC cell migration, invasive
potential and proliferation were specifically abrogated by treatment with the ERK
inhibitor U0126 while JNK inhibitor SP600125 only disrupted IL-33-induced
enhancement of cell viability. Taken together, our data suggest that IL-33/ST2
axis closely associates with poor prognosis of EOC patients, and it promotes
ovarian cancer growth and metastasis through regulating ERK and JNK signaling
pathways. Thus IL-33/ST2 might be potential prognosis markers and therapeutic
targets for EOC patients.
PMID- 26433473
TI - Spotlighted Brains: Optogenetic Activation and Silencing of Neurons.
AB - Optogenetics is revolutionizing cell biology and neuroscience research by
allowing precise biochemical control of neuronal activity through light-activated
channels. Light-induced ion transporters have been used extensively for cellular
activation, and now light-gated inhibitory channels have been discovered. These
represent a key new tool to elucidate the molecular mechanisms underlying
neurological and neuropsychiatric disorders.
PMID- 26433474
TI - Enhancement of Localized Surface Plasmon Resonance polymer based biosensor chips
using well-defined glycopolymers for lectin detection.
AB - Poly(methyl methacrylate) polymer based Localized Surface Plasmon Resonance
biosensor chips were successfully fabricated using glycopolymer brushes carrying
glucose moieties for the detection of concanavalin A. Poly(pentafluorostyrene),
with pre-determined polymer chain lengths, were synthesized via a reversible
addition-fragmentation chain transfer polymerization technique. The synthesized
poly(pentafluorostyrene), was subsequently converted into glycopolymers via a
para-fluoro-thiol "click" reaction and grafted onto the surface of sensor chips.
The "glycocluster effect" induced by pendent carbohydrate moieties enabled a
stronger affinity for concanavalin A binding, which resulted in a dramatic
expansion of the sensors' response range. It was discovered that the longer
polymer brushes did not guarantee additional enhancements for the sensor chips.
Instead, they could lead to higher detection limits. In this study, the limit of
detection for the sensor chips was discovered to be 1.3nmolL(-1) with a saturated
response at 1054.2nmolL(-1). In addition to the superior performance, the
capabilities of the reported sensor chips can be easily manipulated to detect a
diverse range of analytes by "clicking" various sensing elements onto the polymer
brushes.
PMID- 26433475
TI - In-situ preparation, characterization and anticorrosion property of polypropylene
glycol/silver nanoparticles composite for mild steel corrosion in acid solution.
AB - A novel polypropylene glycol/silver nanoparticles (PPG/AgNPs) composite was
prepared in-situ using natural honey as the reducing and capping agent.
Characterization of the composite was done by UV-Vis spectroscopy, FTIR, TEM,
XRD, and EDS. The TEM results reveal that the nanoparticles are spherical in
shape. XRD and EDS results confirm the presence of elemental silver in the
polymer matrix. The influence of the prepared composite on the corrosion
inhibition of mild steel in 0.5M H2SO4 solution was studied by weight loss,
electrochemical, SEM, EDS, and water contact angle measurements. Results show
that PPG/AgNPs is effective inhibitor for mild steel in 0.5M H2SO4 solution and
adsorbs onto the metal surface via chemisorption mechanism. Maximum inhibition
efficiency of 94% is afforded by the highest studied concentration of PPG/AgNPs
at 333K from weight loss measurements. Potentiodynamic polarization results
reveal that the composite acts as a mixed-type corrosion inhibitor. Adsorption of
PPG/AgNPs composite onto the mild steel surface follows Temkin adsorption
isotherm. The SEM, EDS, and water contact angle images confirm the formation of
PPG/AgNPs protective film on the mild steel surface.
PMID- 26433477
TI - A trimodal porous carbon as an effective catalyst for hydrogen production by
methane decomposition.
AB - A new type of porous carbon with an interconnected trimodal pore system is
synthesized by a nanocasting method using nanoparticulated bimodal micro
mesoporous silica particles as the template. The synthesized template and carbon
material are characterized using transmission electron microscopy (TEM), field
emission electron scanning microscopy (FESEM) and nitrogen adsorption-desorption
test. The synthesized carbon material has an extremely high surface area, a large
pore volume and an interconnected pore structure, which could provide abundant
active sites and space for chemical reactions and minimize the diffusion
resistance of the reactants. The resulting carbon is used as the catalyst for
hydrogen production by the thermal decomposition of methane. The catalytic
results show that the as-synthesized carbon in this study produces much higher
methane conversion and hydrogen yield than the commercial carbon materials.
PMID- 26433476
TI - A novel inorganic precipitation-peptization method for VO2 sol and VO2
nanoparticles preparation: Synthesis, characterization and mechanism.
AB - In this paper, a simple, safe and cost-saving precipitation-peptization method
was proposed to prepare VO2 sol by using inorganic VOSO4-NH3?H2O-H2O2 reactants
system in air under room temperature. In this process, VOSO4 was firstly
precipitated to form VO(OH)2, then monometallic species of VO(O2)(OH)(-) were
formed through the coordination between VO(OH)2 and H2O2. The rearrangement of
VO(O2)(OH)(-) in a nonplanar pattern and intermolecular condensation reactions
result in multinuclear species. Finally, VO2 sol is prepared through the
condensation reactions between the multinuclear species. After drying the
obtained sol at 40 degrees C, VO2 xerogel exhibiting monoclinic crystal structure
with the space group of C2/m was prepared. The crystal structure of VO2
nanoparticles was transferred to monoclinic crystal structure with the space
group of P21/c (VO2(M)) by annealing the xerogel at 550 degrees C. Both XRD and
TEM analysis indicated that the nanoparticles possess good crystallinity with
crystallite size of 34.5nm as estimated by Scherrer's method. These results
suggest that the VO2 sol has been prepared successfully through the proposed
simple method.
PMID- 26433478
TI - Stabilizing and destabilizing protein surfactant-based foams in the presence of a
chemical surfactant: Effect of adsorption kinetics.
AB - Stimuli-responsive protein surfactants promise alternative foaming materials that
can be made from renewable sources. However, the cost of protein surfactants is
still higher than their chemical counterparts. In order to reduce the required
amount of protein surfactant for foaming, we investigated the foaming and
adsorption properties of the protein surfactant, DAMP4, with addition of low
concentrations of the chemical surfactant sodium dodecylsulfate (SDS). The
results show that the small addition of SDS can enhance foaming functions of
DAMP4 at a lowered protein concentration. Dynamic surface tension measurements
suggest that there is a synergy between DAMP4 and SDS which enhances adsorption
kinetics of DAMP4 at the initial stage of adsorption (first 60s), which in turn
stabilizes protein foams. Further interfacial properties were revealed by X-ray
reflectometry measurements, showing that there is a re-arrangement of adsorbed
protein-surfactant layer over a long period of 1h. Importantly, the foaming
switchability of DAMP4 by metal ions is not affected by the presence of SDS, and
foams can be switched off by the addition of zinc ions at permissive pH. This
work provides fundamental knowledge to guide formulation using a mixture of
protein and chemical surfactants towards a high performance of foaming at a low
cost.
PMID- 26433479
TI - Tunable ZnO spheres with high anti-biofilm and antibacterial activity via a
simple green hydrothermal route.
AB - A family of distinct ZnO morphologies - hollow, compartmented, core-shell and
full solid ZnO spheres, dispersed or interconnected - is obtained by a simple
hydrothermal route, in the presence of the starch biopolymer. The zinc
carbonaceous precursors were characterized by infrared spectroscopy, thermal
analysis and scanning electron microscopy, while the ZnO spheres, obtained after
the thermal processing, were investigated by X-ray diffraction, Raman
spectroscopy, scanning electron microscopy, UV-VIS spectroscopy,
photoluminescence measurements, antimicrobial, anti-biofilm and flow cytometry
tests. The formation mechanism proposed for this versatile synthesis route is
based on the gelling ability of amylose, one of the starch template constituents,
responsible for the effective embedding of zinc cations into starch prior to its
hydrothermal carbonization. The simple variation of the raw materials
concentration dictates the type of ZnO spheres. The micro-sized ZnO spheres
exhibit high antibacterial and anti-biofilm activity against Gram-positive
(Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli,
Klebsiella pneumoniae, Pseudomonas aeruginosa) reference and methicillin
resistant clinical strains especially for Gram-negative biofilms (P. aeruginosa),
demonstrating great potential for new ZnO anti-biofilm formulations.
PMID- 26433480
TI - Transient Marangoni transport of colloidal particles at the liquid/liquid
interface caused by surfactant convective-diffusion under radial flow.
AB - HYPOTHESIS: Interfacial tension gradients at a liquid/liquid interface drive
Marangoni flows. When colloidal particles are adsorbed to an interface in systems
with spatial and temporal gradients of surfactant concentration, these
interfacial flows can be potentially significant contributors to the direction
and rate of particle transport. EXPERIMENTS: In this work, we use optical
microscopy to measure the interfacial velocities of 5MUm diameter polystyrene
latex particles adsorbed at an oil/water interface, using olive oil to represent
polar oils often encountered in cleaning applications. FINDINGS: On surfactant
adsorption the maximum interfacial velocity scales linearly with bulk surfactant
concentration, even for concentrations exceeding the critical micelle
concentration (CMC). The maximum interfacial velocity weakly decreases with
increasing flow rate, but it varies non-monotonically with the radial distance
from the inlet. Upon surfactant desorption into a rinse solution, the maximum
velocity increases with increasing concentration of the original surfactant
solution, but only up to a plateau near the CMC. These experimental trends are
well-described by a convective-diffusion model for surfactant transport to or
from the liquid/liquid interface coupled with Langmuir-type adsorption, using a
constitutive relation between the interfacial tension gradient and interfacial
velocity based on the interfacial tangential stress jump.
PMID- 26433481
TI - Stability of a compound sessile drop at the axisymmetric configuration.
AB - The equilibrium configuration of compound sessile drops has been calculated
previously in the absence of gravity. Using the Laplace equations, we establish
seven dimensionless parameters describing the axisymmetric configuration in the
presence of gravity. The equilibrium axisymmetric configuration can be either
stable or unstable depending on the fluid properties. A stability criterion is
established by calculating forces on a perturbed Laplacian shape. In the zero
Bond number limit, the stability criterion depends on the density ratio, two
ratios of interfacial tensions, the volume ratio of the two drops, and the
contact angle. We use Surface Evolver to examine the stability of compound
sessile drops at small and large Bond numbers and compare with the zero Bond
number approximation. Experimentally, we realize a stable axisymmetric compound
sessile drop in air, where the buoyancy force exerted by the air is negligible.
Finally, using a pair of fluids in which the density ratio can be tuned nearly
independently of the interfacial tensions, the stability transition is verified
for the axisymmetric configuration. Even though the perturbations are different
for the theory, simulations and experiments, both simulations and experiments
agree closely with the zero Bond number approximation, exhibiting a small
discrepancy at large Bond number.
PMID- 26433482
TI - Astragaloside IV attenuates apoptosis of hypertrophic cardiomyocyte through
inhibiting oxidative stress and calpain-1 activation.
AB - Calpain-1 activation and oxidative stress are two critical factors contributing
to apoptosis of hypertrophic cardiomyocyte. Astragaloside IV (ASIV) exhibits
protective effect against various heart diseases. The present study was designed
to investigate whether the inhibitory effect of ASIV on isoproterenol (ISO)
induced apoptosis of hypertrophic cardiomyocyte was associated with the anti
oxidation and calpain-1 inhibition. Hypertrophy, apoptosis, mitochondrial
oxidative stress and calpain-1 expression were measured in the heart tissue of
Sprague-Dawley (SD) rats and H9C2 cells treated with ISO alone or combination
with ASIV. The results showed that ASIV attenuated apoptotic rate, increased Bcl
2 expression, decreased Bax expression, ameliorated the integrity of
mitochondrial structure and improved mitochondrial membrane potential (MMP).
Moreover, ASIV combination reduced both calpain-1 protein expression and calpain
activity, down-regulated mitochondrial NOX4 (mito-NOX4) expression, increased
activity of mitochondrial superoxide dismutase (mito-SOD) and mitochondrial
catalase (mito-CAT) compared to ISO treated alone. The results suggested that
ASIV exerted anti-apoptosis effect on ISO-induced hypertrophic cardiomyocyte by
attenuating oxidative stress and calpain-1 activation.
PMID- 26433483
TI - Maximizing lipocalin prediction through balanced and diversified training set and
decision fusion.
AB - Lipocalins are short in sequence length and perform several important biological
functions. These proteins are having less than 20% sequence similarity among
paralogs. Experimentally identifying them is an expensive and time consuming
process. The computational methods based on the sequence similarity for
allocating putative members to this family are also far elusive due to the low
sequence similarity existing among the members of this family. Consequently, the
machine learning methods become a viable alternative for their prediction by
using the underlying sequence/structurally derived features as the input.
Ideally, any machine learning based prediction method must be trained with all
possible variations in the input feature vector (all the sub-class input
patterns) to achieve perfect learning. A near perfect learning can be achieved by
training the model with diverse types of input instances belonging to the
different regions of the entire input space. Furthermore, the prediction
performance can be improved through balancing the training set as the imbalanced
data sets will tend to produce the prediction bias towards majority class and its
sub-classes. This paper is aimed to achieve (i) the high generalization ability
without any classification bias through the diversified and balanced training
sets as well as (ii) enhanced the prediction accuracy by combining the results of
individual classifiers with an appropriate fusion scheme. Instead of creating the
training set randomly, we have first used the unsupervised Kmeans clustering
algorithm to create diversified clusters of input patterns and created the
diversified and balanced training set by selecting an equal number of patterns
from each of these clusters. Finally, probability based classifier fusion scheme
was applied on boosted random forest algorithm (which produced greater
sensitivity) and K nearest neighbour algorithm (which produced greater
specificity) to achieve the enhanced predictive performance than that of
individual base classifiers. The performance of the learned models trained on
Kmeans preprocessed training set is far better than the randomly generated
training sets. The proposed method achieved a sensitivity of 90.6%, specificity
of 91.4% and accuracy of 91.0% on the first test set and sensitivity of 92.9%,
specificity of 96.2% and accuracy of 94.7% on the second blind test set. These
results have established that diversifying training set improves the performance
of predictive models through superior generalization ability and balancing the
training set improves prediction accuracy. For smaller data sets, unsupervised
Kmeans based sampling can be an effective technique to increase generalization
than that of the usual random splitting method.
PMID- 26433484
TI - Validating multiplexes for use in conjunction with modern interpretation
strategies.
AB - In response to requests from the forensic community, commercial companies are
generating larger, more sensitive, and more discriminating STR multiplexes. These
multiplexes are now applied to a wider range of samples including complex multi
person mixtures. In parallel there is an overdue reappraisal of profile
interpretation methodology. Aspects of this reappraisal include 1. The need for a
quantitative understanding of allele and stutter peak heights and their
variability, 2. An interest in reassessing the utility of smaller peaks below the
often used analytical threshold, 3. A need to understand not just the occurrence
of peak drop-in but also the height distribution of such peaks, and 4. A need to
understand the limitations of the multiplex-interpretation strategy pair
implemented. In this work we present a full scheme for validation of a new
multiplex that is suitable for informing modern interpretation practice. We
predominantly use GlobalFilerTM as an example multiplex but we suggest that the
aspects investigated here are fundamental to introducing any multiplex in the
modern interpretation environment.
PMID- 26433485
TI - Evaluation of the Illumina((r)) Beta Version ForenSeqTM DNA Signature Prep Kit
for use in genetic profiling.
AB - While capillary electrophoresis-based technologies have been the mainstay for
human identity typing applications, there are limitations with this methodology's
resolution, scalability, and throughput. Massively parallel sequencing (MPS)
offers the capability to multiplex multiple types of forensically-relevant
markers and multiple samples together in one run all at an overall lower cost per
nucleotide than traditional capillary electrophoresis-based methods; thus,
addressing some of these limitations. MPS also is poised to expand forensic
typing capabilities by providing new strategies for mixture deconvolution with
the identification of intra-STR allele sequence variants and the potential to
generate new types of investigative leads with an increase in the overall number
and types of genetic markers being analyzed. The beta version of the Illumina
ForenSeq DNA Signature Prep Kit is a MPS library preparation method with a
streamlined workflow that allows for targeted amplification and sequencing of 63
STRs and 95 identity SNPs, with the option to include an additional 56 ancestry
SNPs and 22 phenotypic SNPs depending on the primer mix chosen for amplification,
on the MiSeq desktop sequencer (Illumina). This study was divided into a series
of experiments that evaluated reliability, sensitivity of detection, mixture
analysis, concordance, and the ability to analyze challenged samples. Genotype
accuracy, depth of coverage, and allele balance were used as informative metrics
for the quality of the data produced. The ForenSeq DNA Signature Prep Kit
produced reliable, reproducible results and obtained full profiles with DNA input
amounts of 1ng. Data were found to be concordant with current capillary
electrophoresis methods, and mixtures at a 1:19 ratio were resolved accurately.
Data from the challenged samples showed concordant results with current DNA
typing methods with markers in common and minimal allele drop out from the large
number of markers typed on these samples. This set of experiments indicates the
beta version of the ForenSeq DNA Signature Prep Kit is a valid tool for forensic
DNA typing and warrants full validation studies of this MPS technology.
PMID- 26433486
TI - High resource-capture and -use efficiency, and effective antioxidant protection
contribute to the invasiveness of Alnus formosana plants.
AB - To investigate the traits contributing to the invasiveness of Alnus formosana and
the mechanisms underlying its invasiveness, we compared A. formosana with its
native congener (Alnus cremastogyne) under three light treatments (13%, 56%, and
100%). The consistently higher plant height, total leaf area, light-saturated
photosynthetic rate (A(max)), light saturation point (LSP), light compensation
point (LCP), respiration efficiency (RE), and non-photochemical quenching
coefficient (NPQ) but lower root mass fraction (RMF) and specific leaf area (SLA)
of the invader than of its native congener contributed to the higher RGR and
total biomass of A. formosana across light regimes. The total biomass and RGR of
the invader increased markedly with increased RMF, A(max), LSP, LCP, RE, stomatal
conductance (G(s)) and total leaf area. Furthermore, compared with the native
species, the higher plasticity index in plant height, RMF, leaf mass fraction
(LMF), SMF, SLA, A(max) and dark respiration rate (R(d)) within the range of
total light contributed to the higher performance of the invader. In addition,
the activities of antioxidant enzymes were higher in the invader compared to the
native, contributing to its invasion success under high/low light via
photoprotection. With a decrease in light level, superoxide dismutase (SOD) and
catalase (CAT) activities increased significantly, whereas total carotenoid (Car)
and total chlorophyll (Chl) decreased; ascorbate peroxidase (APX) and glutathione
reductase (GR) activities remained unchanged. These responses may help the
invader to spread and invade a wide range of habitats and form dense
monocultures, displacing native plant species. The results suggest that both
resource capture-related traits (morphological and photosynthetic) and adaptation
related traits (antioxidant protection) contribute to the competitive advantage
of the invader.
PMID- 26433487
TI - Predictors of Pathologic Complete Response After Neoadjuvant Treatment for Rectal
Cancer: A Multicenter Study.
AB - BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemoradiation
(CRT) for rectal cancer is associated with better long-term outcomes, and is used
as an early indicator of response to novel agents. To assess the rate and
predictors of pCR, we performed a retrospective multicenter study involving 5
Canadian cancer centers. PATIENTS AND METHODS: Cancer registries identified
consecutive patients with locally advanced rectal adenocarcinoma from the Tom
Baker Cancer Centre, Cross Cancer Institute, British Columbia Cancer Agency,
Ottawa Hospital Cancer Centre, and the Dr H. Bliss Murphy Cancer Centre who
received fluoropyrimidine-based CRT and had curative intent surgery from 2005 to
2012. Patient, tumor, and therapy characteristics were correlated with response.
RESULTS: Of the 891 patients included, 885 patients had pCR data available. Of
the included patients, 161 (18.2%) had a pCR to CRT, and 724 (81.8%) did not.
Patients with a pCR had a lower pretreatment carcinoembryonic antigen (CEA)
level, and higher hemoglobin level in univariate analysis. In multivariable
analysis, statin use at baseline (odds ratio [OR], 1.7; 95% confidence interval
[CI], 1.02-2.92; P = .04), lower pretreatment CEA level (OR, 1.03; 95% CI, 1.01
1.06; P = .03), and distance closer to anal verge (OR, 1.07; 95% CI, 1.01-1.15; P
= .04) were significant predictors of pCR. The 3-year disease-free survival was
86% in those with a pCR versus 62.5% in those without a pCR (P < .0001) and pCR
was associated with improved overall survival (hazard ratio, 0.29; 95% CI, 0.17
0.51; P < .0001). CONCLUSION: Lower pretreatment CEA level, proximity to anal
verge, and statin use are predictors of pCR in our large retrospective cohort.
Clinical trials to investigate statins combined with neoadjuvant CRT might be
warranted.
PMID- 26433488
TI - Nanomedicine-mediated cancer stem cell therapy.
AB - Circumstantial evidence suggests that most tumours are heterogeneous and contain
a small population of cancer stem cells (CSCs) that exhibit distinctive self
renewal, proliferation and differentiation capabilities, which are believed to
play a crucial role in tumour progression, drug resistance, recurrence and
metastasis in multiple malignancies. Given that the existence of CSCs is a
primary obstacle to cancer therapy, a tremendous amount of effort has been put
into the development of anti-CSC strategies, and several potential approaches to
kill therapeutically-resistant CSCs have been explored, including inhibiting ATP
binding cassette transporters, blocking essential signalling pathways involved in
self-renewal and survival of CSCs, targeting CSCs surface markers and destroying
the tumour microenvironment. Meanwhile, an increasing number of therapeutic
agents (e.g. small molecule drugs, nucleic acids and antibodies) to selectively
target CSCs have been screened or proposed in recent years. Drug delivery
technology-based approaches hold great potential for tackling the limitations
impeding clinical applications of CSC-specific agents, such as poor water
solubility, short circulation time and inconsistent stability. Properly designed
nanocarrier-based therapeutic agents (or nanomedicines) offer new possibilities
of penetrating CSC niches and significantly increasing therapeutic drug
accumulation in CSCs, which are difficult for free drug counterparts. In
addition, intelligent nanomedicine holds great promise to overcome pump-mediated
multidrug resistance which is driven by ATP and to decrease detrimental effects
on normal somatic stem cells. In this review, we summarise the distinctive
biological processes related to CSCs to highlight strategies against inherently
drug-resistant CSCs. We then focus on some representative examples that give a
glimpse into state-of-the-art nanomedicine approaches developed for CSCs
elimination. A perspective on innovative therapeutic strategies and the potential
direction of nanomedicine-based CSC therapy in the near future is also presented.
PMID- 26433490
TI - Microarray analyses to quantify advantages of 2D and 3D hydrogel culture systems
in maintaining the native valvular interstitial cell phenotype.
AB - Valvular interstitial cells (VICs) actively maintain and repair heart valve
tissue; however, persistent activation of VICs to a myofibroblast phenotype can
lead to aortic stenosis. To better understand and quantify how microenvironmental
cues influence VIC phenotype and myofibroblast activation, we compared expression
profiles of VICs cultured on poly(ethylene glycol) (PEG) gels to those cultured
on tissue culture polystyrene (TCPS), as well as fresh isolates. In general, VICs
cultured in hydrogel matrices had lower levels of activation (<10%), similar to
levels seen in healthy valve tissue, while VICs cultured on TCPS were ~75%
activated myofibroblasts. VICs cultured on TCPS also exhibited a higher magnitude
of perturbations in gene expression than soft hydrogel cultures when compared to
the native phenotype. Using peptide-modified PEG gels, VICs were seeded on (2D),
as well as encapsulated in (3D), matrices of the same composition and modulus.
Despite similar levels of activation, VICs cultured in 2D had distinct variations
in transcriptional profiles compared to those in 3D hydrogels. Genes related to
cell structure and motility were particularly affected by the dimensionality of
the culture platform, with higher expression levels in 2D than in 3D. These
results indicate that dimensionality may play a significant role in dictating
cell phenotype (e.g., through differences in polarity, diffusion of soluble
signals), and emphasize the importance of using multiple metrics when
characterizing cell phenotype.
PMID- 26433491
TI - Vitamin D3 modulates the innate immune response through regulation of the hCAP
18/LL-37 gene expression and cytokine production.
AB - INTRODUCTION: The steroid hormone metabolite of vitamin D3, 1alpha,25
dihydroxyvitamin D3 (1,25D3), promotes osteogenic activity and regulates calcium
and phosphate metabolism, which are actions regarded as classical vitamin D
regulated functions. Besides its role in these processes, 1,25D3 also seems
implicated in the host defense against microbial/pro-inflammatory attacks. Low
serum levels of vitamin D3 (vitamin D deficiency) are associated with
osteoporosis and increased risk of fractures but also inflammatory diseases and
their disease progression, presumably via mechanisms associated with 1,25D3
evoked modulation of the innate immune system. 1,25D3 has been reported to
modulate many inflammatory responses, suggesting that it regulates multiple
transcriptional targets within the inflammatory system. RESULTS: Experimental
studies in various experimental systems show that 1,25D3 differentially regulates
the production of pro-inflammatory cytokines and chemokines depending on cell
type. Importantly, many reports show that 1,25D3 up-regulates expression of the
human antimicrobial peptide hCAP-18/LL-37 gene. The hCAP-18/LL-37 gene seems
indeed to be an important transcriptional target for 1,25D3. However, only
limited evidence is presented showing that 1,25D3 consistently increases the
amount of biologically active LL-37 peptide. CONCLUSION: In the present review,
we discuss 1,25D3-induced down-regulation of cytokine/chemokine production and
stimulation of hCAP-18/LL-37 gene expression which represent two very important
pathways for 1,25D3-evoked regulation of the innate immune response.
PMID- 26433489
TI - Cell surface glycoengineering improves selectin-mediated adhesion of mesenchymal
stem cells (MSCs) and cardiosphere-derived cells (CDCs): Pilot validation in
porcine ischemia-reperfusion model.
AB - Promising results are emerging in clinical trials focused on stem cell therapy
for cardiology applications. However, the low homing and engraftment of the
injected cells to target tissue continues to be a problem. Cellular
glycoengineering can address this limitation by enabling the targeting of stem
cells to sites of vascular injury/inflammation. Two such glycoengineering methods
are presented here: i. The non-covalent incorporation of a P-selectin
glycoprotein ligand-1 (PSGL-1) mimetic 19Fc[FUT7(+)] via lipid-protein G fusion
intermediates that intercalate onto the cell surface, and ii. Over-expression of
the alpha(1,3)fucosyltransferse FUT7 in cells. Results demonstrate the efficient
coupling of 19Fc[FUT7(+)] onto both cardiosphere-derived cells (CDCs) and
mesenchymal stem cells (MSCs), with coupling being more efficient when using
protein G fused to single-tailed palmitic acid rather than double-tailed DOPE
(1,2-dioleoyl-sn-glycero-3-phosphoethanolamine). This non-covalent cellular
modification was mild since cell proliferation and stem-cell marker expression
was unaltered. Whereas coupling using 19Fc[FUT7(+)] enhanced cell capture on
recombinant P-selectin or CHO-P cell surfaces, alpha(1,3)fucosylation was
necessary for robust binding to E-selectin and inflamed endothelial cells under
shear. Pilot studies confirm the safety and homing efficacy of the modified stem
cells to sites of ischemia-reperfusion in the porcine heart. Overall,
glycoengineering with physiological selectin-ligands may enhance stem cell
engraftment.
PMID- 26433493
TI - Penises not required: a systematic review of the potential for human
papillomavirus horizontal transmission that is non-sexual or does not include
penile penetration.
AB - The primary mode of human papillomavirus (HPV) transmission is through
penetrative sex; however, there is evidence of other modes of transmission. No
systematic review was found that focussed on HPV horizontal transmission that is
not penocentric. A systematic review of the literature by searching Medline
(Ovid), PubMed (NLM) and Embase (Ovid) was conducted to retrieve articles
published from 1946 to March 2014. Studies that suggested evidence of non-sexual
or non-penetrative sexual transmission of alpha-HPV genotypes were included.
After review of 2061 titles and abstracts, 51 studies were abstracted. Fifteen
studies examined HPV fomites from medical settings or public environments, and 36
examined HPV in humans. Human papillomavirus DNA was detected in the genital
tract of female virgins, with prevalence estimates ranging from 0% to 51.1%. HPV
transmission from hands to genitals or genitals to hands was reported for both
sexes and heterosexual couples. Other studies commonly found HPV on surfaces in
medical settings and public environments. Further studies on non-sexual and non
penetrative sexual transmission are needed to understand the complexity of HPV
transmission. Health-care policies may need to be reassessed/established to
ensure the safety of medical instruments and to reduce the risk of HPV nosocomial
infection.
PMID- 26433492
TI - What makes health impact assessments successful? Factors contributing to
effectiveness in Australia and New Zealand.
AB - BACKGROUND: While many guidelines explain how to conduct Health Impact
Assessments (HIAs), less is known about the factors that determine the extent to
which HIAs affect health considerations in the decision making process. We
investigated which factors are associated with increased or reduced effectiveness
of HIAs in changing decisions and in the implementation of policies, programs or
projects. This study builds on and tests the Harris and Harris-Roxas' conceptual
framework for evaluating HIA effectiveness, which emphasises context, process and
output as key domains. METHODS: We reviewed 55 HIA reports in Australia and New
Zealand from 2005 to 2009 and conducted surveys and interviews for 48 of these
HIAs. Eleven detailed case studies were undertaken using document review and
stakeholder interviews. Case study participants were selected through purposeful
and snowball sampling. The data were analysed by thematic content analysis.
Findings were synthesised and mapped against the conceptual framework. A
stakeholder forum was utilised to test face validity and practical adequacy of
the findings. RESULTS: We found that some features of HIA are essential, such as
the stepwise but flexible process, and evidence based approach. Non-essential
features that can enhance the impact of HIAs include capacity and experience;
'right person right level'; involvement of decision-makers and communities; and
relationships and partnerships. There are contextual factors outside of HIA such
as fit with planning and decision making context, broader global context and
unanticipated events, and shared values and goals that may influence a HIA.
Crosscutting factors include proactive positioning, and time and timeliness.
These all operate within complex open systems, involving multiple decision
makers, levels of decision-making, and points of influence. The Harris and Harris
Roxas framework was generally supported. CONCLUSION: We have confirmed previously
identified factors influencing effectiveness of HIA and identified new factors
such as proactive positioning. Our findings challenge some presumptions about
'right' timing for HIA and the rationality and linearity of decision-making
processes. The influence of right timing on decision making needs to be seen
within the context of other factors such as proactive positioning. This research
can help HIA practitioners and researchers understand and identify what can be
enhanced within the HIA process. Practitioners can adapt the flexible HIA process
to accommodate the external contextual factors identified in this report.
PMID- 26433494
TI - Maryland's Helicopter Emergency Medical Services Experience From 2001 to 2011:
System Improvements and Patients' Outcomes.
AB - STUDY OBJECTIVE: Helicopter emergency medical services (EMS) has become a well
established component of modern trauma systems. It is an expensive, limited
resource with potential safety concerns. Helicopter EMS activation criteria
intended to increase efficiency and reduce inappropriate use remain elusive and
difficult to measure. This study evaluates the effect of statewide field trauma
triage changes on helicopter EMS use and patient outcomes. METHODS: Data were
extracted from the helicopter EMS computer-aided dispatch database for in-state
scene flights and from the state Trauma Registry for all trauma patients directly
admitted from the scene or transferred to trauma centers from July 1, 2000, to
June 30, 2011. Computer-aided dispatch flights were analyzed for periods
corresponding to field triage protocol modifications intended to improve system
efficiency. Outcomes were separately analyzed for trauma registry patients by
mode of transport. RESULTS: The helicopter EMS computer-aided dispatch data set
included 44,073 transports. There was a statewide decrease in helicopter EMS
usage for trauma patients of 55.9%, differentially affecting counties closer to
trauma centers. The Trauma Registry data set included 182,809 patients (37,407
helicopter transports, 128,129 ambulance transports, and 17,273 transfers). There
was an increase of 21% in overall annual EMS scene trauma patients transported;
ground transports increased by 33%, whereas helicopter EMS transports decreased
by 49%. Helicopter EMS patient acuity increased, with an attendant increase in
patient mortality. However, when standardized with W statistics, both helicopter
EMS- and ground-transported trauma patients showed sustained improvement in
mortality. CONCLUSION: Modifications to state protocols were associated with
decreased helicopter EMS use and overall improved trauma patient outcomes.
PMID- 26433495
TI - The unfinished agenda of women's reproductive health.
PMID- 26433496
TI - Moving beyond silos: How do we provide distributed personalized medicine to
pregnant women everywhere at scale? Insights from PRE-EMPT.
AB - While we believe that pre-eclampsia matters-because it remains a leading cause of
maternal and perinatal morbidity and mortality worldwide-we are convinced that
the time has come to look beyond single clinical entities (e.g. pre-eclampsia,
postpartum hemorrhage, obstetric sepsis) and to look for an integrated approach
that will provide evidence-based personalized care to women wherever they
encounter the health system. Accurate outcome prediction models are a powerful
way to identify individuals at incrementally increased (and decreased) risks
associated with a given condition. Integrating models with decision algorithms
into mobile health (mHealth) applications could support community and first level
facility healthcare providers to identify those women, fetuses, and newborns most
at need of facility-based care, and to initiate lifesaving interventions in their
communities prior to transportation. In our opinion, this offers the greatest
opportunity to provide distributed individualized care at scale, and soon.
PMID- 26433497
TI - Prevention of type 2 diabetes among women with prior gestational diabetes
mellitus.
AB - The morbidity and mortality rates related to diabetes are constantly rising, as
well as those for other noncommunicable diseases. The epidemic is spreading
throughout the world, in both low- and high-resource countries. Prevention is a
key aspect in the battle against the disease and obstetricians play a critical
role in the fight. Prevention starts in utero-for the diabetic mother, her
infant, and future generations. The postpartum period should not be neglected
because it provides another window of opportunity to address prevention. Data on
the prevention of type 2 diabetes among women diagnosed with gestational diabetes
are discussed.
PMID- 26433498
TI - New drug regimens for HIV in pregnancy and a national strategic plan to manage
HIV: A South African perspective.
AB - In South Africa, new drug regimens (WHO treatment Option B) used to manage HIV
infection in pregnancy and the national strategic plan on HIV have resulted in
improved health outcomes. Among these outcomes are reductions in the following:
mother-to-child transmission (MTCT) of HIV to 2.4%; maternal deaths attributable
to HIV; and adverse reactions due to antiretroviral therapy (ART). The present
article describes these new drug regimens and the national strategic HIV
management plan, as well as their challenges and the implications of improved
health outcomes. Such outcomes imply that further decreases in MTCT of HIV, and
HIV attributable maternal deaths are possible if potential challenges are
addressed and treatment option B+ offered. A confidential enquiry into each case
of MTCT is advocated to reduce vertical transmission rates to zero levels.
PMID- 26433499
TI - Quality assurance: The 10-Group Classification System (Robson classification),
induction of labor, and cesarean delivery.
AB - Quality assurance in labor and delivery is needed. The method must be simple and
consistent, and be of universal value. It needs to be clinically relevant,
robust, and prospective, and must incorporate epidemiological variables. The 10
Group Classification System (TGCS) is a simple method providing a common starting
point for further detailed analysis within which all perinatal events and
outcomes can be measured and compared. The system is demonstrated in the present
paper using data for 2013 from the National Maternity Hospital in Dublin,
Ireland. Interpretation of the classification can be easily taught. The standard
table can provide much insight into the philosophy of care in the population of
women studied and also provide information on data quality. With standardization
of audit of events and outcomes, any differences in either sizes of groups,
events or outcomes can be explained only by poor data collection, significant
epidemiological variables, or differences in practice. In April 2015, WHO
proposed that the TGCS (also known as the Robson classification) is used as a
global standard for assessing, monitoring, and comparing cesarean delivery rates
within and between healthcare facilities.
PMID- 26433500
TI - Cancer of the cervix: Early detection and cost-effective solutions.
AB - Cervical cancer is known to be a preventable disease through the detection of
cervical cancer precursors, historically using cytology of the cervix as the
primary screening test. Over 85% of cervical cancer cases and deaths occur in low
resource countries. Alternatives to cytology have been investigated with the
strongest possibilities being visual inspection with acetic acid (VIA) and HPV
DNA testing. HPV DNA testing has been shown in randomized trials to be
significantly more sensitive for the detection of cervical cancer precursors than
either cytology or VIA. In this paper we argue that prevention really does cost
less than cure, or that prevention and treatment of cancer costs less than no
prevention, in effect just treatment, of cancer. The true cost savings of
prevention will include a more difficult assessment of the socioeconomic savings
associated with longer, healthier lives for women in their prime who have a major
role in supporting their families.
PMID- 26433501
TI - Strengthening accountability to end preventable maternal deaths.
AB - The present paper describes the ongoing efforts to revitalize the accountability
of national governments toward preventable maternal deaths. Maternal death
reviews are included in the national health policies of the majority of countries
contributing 95% of global maternal deaths. However in actual practice, the
extent of implementation and follow-up of recommended actions on lessons learnt
from maternal death reviews is inadequate. This paper describes and discusses the
role of the Maternal Death Surveillance and Response (MDSR) system in
strengthening accountability and ending preventable maternal deaths. MDSR
provides a surveillance tool for timely information on where, when, and why
maternal deaths occur, builds on maternal death reviews, and includes the missing
"response" component for improving quality of care and preventing maternal
deaths.
PMID- 26433502
TI - HPV vaccination: The most pragmatic cervical cancer primary prevention strategy.
AB - The evidence that high-risk HPV infections cause cervical cancers has led to two
new approaches for cervical cancer control: vaccination to prevent HPV
infections, and HPV screening to detect and treat cervical precancerous lesions.
Two vaccines are currently available: quadrivalent vaccine targeting oncogenic
HPV types 16, 18, 6, and 11, and bivalent vaccine targeting HPV 16 and 18. Both
vaccines have demonstrated remarkable immunogenicity and substantial protection
against persistent infection and high-grade cervical cancer precursors caused by
HPV 16 and 18 in HPV-naive women, and have the potential to prevent 70% of
cervical cancers in adequately vaccinated populations. HPV vaccination is now
implemented in national programs in 62 countries, including some low- and middle
income countries. The early findings from routine national programs in high
income countries are instructive to encourage low- and middle-income countries
with a high risk of cervical cancer to roll out HPV vaccination programs and to
introduce resource-appropriate cervical screening programs.
PMID- 26433503
TI - A historic and scientific review of breast cancer: The next global healthcare
challenge.
AB - Breast cancer is fast becoming the leading cause of oncologic morbidity and
mortality among women worldwide. Demographic changes in Asia, Southeast Asia, and
South America will further accelerate this trend. Different specialties are
involved in the treatment of breast cancer patients: gynecology, surgery,
pathology, hematology/oncology, radiology, radiation oncology, and nuclear
medicine. Optimal results are seen in countries providing standardized breast
cancer care in certified breast centers. The present article provides an overview
of current state-of-the-art treatment strategies and explains the contributions
of different specialties to optimal and individualized care for breast cancer
patients. Breast cancer will be one of the most important health issues facing
physicians involved with women's health and a basic understanding of current
treatment objectives will be essential medical knowledge for everyone taking care
of female patients.
PMID- 26433504
TI - Adolescent sexual and reproductive health: The global challenges.
AB - Adolescent sexual and reproductive health (ASRH) has been overlooked historically
despite the high risks that countries face for its neglect. Some of the
challenges faced by adolescents across the world include early pregnancy and
parenthood, difficulties accessing contraception and safe abortion, and high
rates of HIV and sexually transmitted infections. Various political, economic,
and sociocultural factors restrict the delivery of information and services;
healthcare workers often act as a barrier to care by failing to provide young
people with supportive, nonjudgmental, youth-appropriate services. FIGO has been
working with partners and its member associations to break some of these barriers
enabling obstetricians and gynecologists to effect change in their countries and
promote the ASRH agenda on a global scale.
PMID- 26433505
TI - Ending preventable newborn deaths in a generation.
AB - The end of the Millennium Development Goal (MDG) era was marked in 2015, and
while maternal and child mortality have been halved, MGD 4 and MDG 5 are off
track at the global level. Reductions in neonatal death rates (age <1 month) lag
behind those for post-neonates (age 1-59 months), and stillbirth rates (omitted
from the MDGs) have been virtually unchanged. Hence, almost half of under-five
deaths are newborns, yet about 80% of these are preventable using cost-effective
interventions. The Every Newborn Action Plan has been endorsed by the World
Health Assembly and ratified by many stakeholders and donors to reduce neonatal
deaths and stillbirths to 10 per 1000 births by 2035. The plan provides an
evidence-based framework for scaling up of essential interventions across the
continuum of care with the potential to prevent the deaths of approximately three
million newborns, mothers, and stillbirths every year. Two million stillbirths
and newborns could be saved by care at birth and care of small and sick newborns,
giving a triple return on investment at this key time. Commitment, investment,
and intentional leadership from global and national stakeholders, including all
healthcare professionals, can make these ambitious goals attainable.
PMID- 26433506
TI - The global epidemic of abuse and disrespect during childbirth: History, evidence,
interventions, and FIGO's mother-baby friendly birthing facilities initiative.
AB - Recent evidence indicates that disrespectful/abusive/coercive service delivery by
skilled providers in facilities, which results in actual or perceived poor
quality of care, is directly and indirectly associated with adverse maternal and
newborn outcomes. The present article reviews the evidence for
disrespectful/abusive care during childbirth in facilities (DACF), describes
examples of DACF, discusses organizations active in a rights-based respectful
maternity care movement, and enumerates some strategies and interventions that
have been identified to decrease DACF. It concludes with a discussion of one
strategy, which has been recently implemented by FIGO with global partners-the
International Pediatrics Association, International Confederation of Midwives,
the White Ribbon Alliance, and WHO. This strategy, the Mother and Baby Friendly
Birth Facility (MBFBF) Initiative, is a criterion-based audit process based on
human rights' doctrines, and modeled on WHO/UNICEF's Baby Friendly Facility
Initiative.
PMID- 26433507
TI - What can obstetrician/gynecologists do to support abortion access?
AB - Unsafe abortion causes approximately 13% of all maternal deaths worldwide, with
higher rates in areas where abortion access is restricted. Because safe abortion
is so low risk, if all women who needed an abortion could access safe care, this
rate would drop dramatically. As women's health providers and advocates,
obstetrician/gynecologists can support abortion access. By delivering high
quality, evidence-based care ourselves, supporting other providers who perform
abortion, helping women who access abortion in the community, providing second
trimester care, and improving contraceptive uptake, we can decrease morbidity and
mortality from unsafe abortion.
PMID- 26433508
TI - Evidence supporting broader access to safe legal abortion.
AB - Unsafe abortion continues to be a major cause of maternal death; it accounts for
14.5% of all maternal deaths globally and almost all of these deaths occur in
countries with restrictive abortion laws. A strong body of accumulated evidence
shows that the simple means to drastically reduce unsafe abortion-related
maternal deaths and morbidity is to make abortion legal and institutional
termination of pregnancy broadly accessible. Despite this evidence, abortion is
denied even when the legal condition for abortion is met. The present article
aims to contribute to a better understanding that one can be in favor of greater
access to safe abortion services, while at the same time not be "in favor of
abortion," by reviewing the evidence that indicates that criminalization of
abortion only increases mortality and morbidity without decreasing the incidence
of induced abortion, and that decriminalization rapidly reduces abortion-related
mortality and does not increase abortion rates.
PMID- 26433509
TI - Emergency obstetric care: Making the impossible possible through task shifting.
AB - Task shifting-moving tasks to healthcare workers with a shorter training-for
emergency obstetric care (EmOC) can potentially improve access to lifesaving
interventions and thereby contribute to reducing maternal and neonatal morbidity
and mortality. The present paper reviews studies on task shifting for the
provision of EmOC. Most studies were performed in Sub-Saharan Africa and South
Asia and focused primarily on task shifting for the performance of cesarean
deliveries. Cesarean delivery rates increased following EmOC training without
significant increase in adverse outcomes. The paper discusses the advantages and
disadvantages of task shifting in EmOC and the role of this approach in improving
maternal and newborn health in the short and long term.
PMID- 26433510
TI - Global trends in use of long-acting reversible and permanent methods of
contraception: Seeking a balance.
AB - The global trend shows that the use of permanent contraception to prevent
unintended pregnancy is high. Although the trend also shows a rise in the use of
long-acting reversible methods, these are still underutilized despite having
contraceptive as well as non-contraceptive benefits. Lack of knowledge among
women, dependence on the provider for information, and provider bias for
permanent contraception are cited as reasons for this reduced uptake. Training of
healthcare providers and increased patient awareness about the effectiveness of
long-acting reversible contraceptive methods will increase their uptake and help
prevent unintended pregnancies.
PMID- 26433511
TI - Global efforts for effective training in fistula surgery.
AB - Obstetric fistulas continue to be a problem in low- and middle-income nations,
affecting women of childbearing age during pregnancy and labor and resulting in
debilitating urinary and/or fecal incontinence. Historically, this predicament
also affected women in high-income nations until the middle of the last century.
This is not a "new world" crisis therefore, but simply one of economic and health
development. In the last two decades, new global initiatives have been instituted
to improve training and education in preventative and curative fistula treatment
by developing a unified and competency-based learning tool by surgeons in the
field in partnership with FIGO and its global partners. This modern approach to
the management of a devastating condition can only serve to achieve the WHO
objective of health security for women throughout their life span.
PMID- 26433512
TI - Task shifting: A key strategy in the multipronged approach to reduce maternal
mortality in India.
AB - Task shifting from specialist to nonspecialist doctors (NSDs) is an important
strategy that has been implemented in India to overcome the critical shortage of
healthcare workers by using the human resources available to serve the vast
population, particularly in rural areas. A competency-based training program in
comprehensive emergency obstetric care was implemented to train and certify NSDs.
Trained NSDs were able to provide key services in maternal health, which
contribute toward reductions in maternal morbidity and mortality. The present
article provides an overview of the maternal health challenges, shares important
steps in program implementation, and shows how challenges can be overcome. The
lessons learned from this experience contribute to understanding how task
shifting can be used to address large-scale public health issues in low-resource
countries and in particular solutions to address maternal health issues.
PMID- 26433513
TI - The role of health professional organizations in improving maternal and newborn
health: The FIGO LOGIC experience.
AB - The FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC)
Initiative in Maternal and Newborn Health improved the internal and external
capacity of eight national professional organizations of obstetrics and
gynecology in six African and two Asian countries. The initiative was funded by a
grant from the Bill and Melinda Gates Foundation and had three key objectives: to
support the eight FIGO member associations to strengthen their capacity to work
effectively; to influence national policies on maternal and newborn health; and
to work toward improving clinical practice in this area. Through improved
capacity, and underpinned by Memoranda of Understanding with their governments,
the associations influenced national policy in maternal and newborn health,
impacted clinical care through the development of over forty national clinical
guidelines, delivered national curricula, trained clinical and management staff,
and led the development of national maternal death and near-miss review programs.
PMID- 26433514
TI - Targeting immune checkpoints: New opportunity for mesothelioma treatment?
AB - Malignant pleural mesothelioma is an aggressive cancer linked to asbestos
exposure in most patients. Due to the long latency between exposure and
presentation, incidence is expected to further increase in the next decade,
despite the ban on asbestos import which occurred at the end of last century in
industrialized countries. Platinum-based palliative chemotherapy is the only
treatment with proven benefit on outcome, resulting in selected patients in a
median overall survival of about 1 year. Therefore, there is room for therapeutic
improvement using a new strategy to prolong survival. Dealing with cancer cell
induced immunosuppression is a promising approach. Reactivating immune responses
that are silenced by immune checkpoints recently gained a lot of interest.
Checkpoint blockade has already shown promising preclinical and clinical results
in several cancer types and is currently also being investigated in mesothelioma.
Here, we discuss the expression patterns and mechanisms of action of CTLA-4 and
PD-1 as the two most studied and of TIM-3 and LAG-3 as two interesting upcoming
immune checkpoints. Furthermore, we review the clinical results of molecules
blocking these immune checkpoints and point out their future opportunities with a
special focus on mesothelioma.
PMID- 26433516
TI - The Clinical Application of Strain: Raising the Standard.
PMID- 26433515
TI - Echocardiographic Identification of Acute Cellular Rejection in Heart Transplant
Recipients.
PMID- 26433517
TI - Celebrating Sonographers All Year.
PMID- 26433518
TI - Injury prevention for sonographers.
PMID- 26433519
TI - The Expanding Role of Peri-Procedural Echocardiography for Guidance of
Transcatheter Structural Heart Interventions.
PMID- 26433520
TI - Determinants of Operative Mortality in Patients With Ruptured Acute Type A Aortic
Dissection.
AB - BACKGROUND: Acute type A aortic dissection (ATAAD) is a surgical emergency
associated with high mortality and morbidity. We analyzed our 15-year experience
in the management of ruptured ATAAD (rATAAD) and non-rATAAD to determine the
predictors of early and late mortality. METHODS: We reviewed all cases with ATAAD
between 1999 and 2014. Patients were grouped into rATAAD and non-rATAAD based on
intraoperative confirmation. Clinical data on preoperative characteristics and in
hospital and long-term outcomes were analyzed to determine risk factors for early
and long-term mortality. Survival was analyzed using Kaplan-Meier and log rank
statistics. RESULTS: Of the 489 total ATAAD repairs, 75 patients (15.3%) had
rATAAD. The rATAAD patients were older compared with non-rATAAD (64.4 +/- 16.2
versus 57.3 +/- 14.2 years, respectively; p = 0.0001) and commonly female (31 of
75 [41.3%] versus 107 of 414 [25.9%], respectively; p = 0.006). Early mortality
was higher among rATAAD patients that among non-rATAAD patients (19 of 75 [25.3%]
versus 48 of 414 [11.6%], respectively; p = 0.002); predictors included rupture,
age, malperfusion syndrome, and coronary artery disease. Patients aged 70 years
or more with malperfusion syndrome had a 7.7-fold risk of 24-hour mortality (p =
0.0003) that was augmented by rATAAD (p = 0.004). Long-term survival was lower
among rATAAD than non-rATAAD (57.4% versus 78.2%, respectively, at 5 years; p <
0.0001); independent predictors included rupture (p = 0.01), low glomerular
filtration rate (p = 0.001), and high-risk group (p = 0.004). These risk factors
were used to construct a predictive model for estimating the probability of early
mortality in ATAAD. CONCLUSIONS: Rupture is associated with significantly higher
mortality in ATAAD. This predictive model provides surgical risk assessment for
early mortality after rATAAD. For acceptable surgical candidates, immediate
aortic repair can provide favorable outcomes.
PMID- 26433521
TI - Contributory Role of Fluorine 18-Fluorodeoxyglucose Positron Emission
Tomography/Computed Tomography in the Diagnosis and Clinical Management of
Infections in Patients Supported With a Continuous-Flow Left Ventricular Assist
Device.
AB - BACKGROUND: The current study sought to demonstrate the advantages offered by
fluorine 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed
tomography (PET/CT) in patients supported with continuous-flow left ventricular
assist devices (CF-LVADs) in detecting infection and the consequent effect on
clinical decisions. METHODS: Between April 2009 and September 2013, 40 PET
examinations were performed in 31 patients (78.1% men; mean age, 51.0 +/- 14.9
years) supported with a CF-LVAD. In group A (19 examinations in 14 patients),
PET/CT was performed to detect infectious focus in patients without external
signs of driveline involvement but with at least two of the following infection
signs: recurrent fever, positive blood culture, or elevated infectious
indicators. In group B (21 examinations in 17 patients), PET/CT aimed to assess
the internal extension of infection in patients with external signs of driveline
infection. RESULTS: In 50% of the cases of the patients in group A, abnormal
(18)F-FDG uptake (9 patients) was related to VAD components. Matching the results
with the final diagnosis, we reported 9 true-positive, 8 true-negative, no false
negative, and 2 false-positive findings. New information unrelated to VAD was
found in 9 patients (50%): pneumonia in 3, colon diverticulitis in 3, sternal
dehiscence in 1, paravertebral abscess in 1, and erysipelas in 1. In group B,
superficial abnormal (18)F-FDG uptake was found at the piercing site of the
driveline in 2 patients, deeper extension of infection along the driveline in 10,
initial involvement of the pump housing in 2, and full involvement of the device
in 4. These findings contributed to changing the clinical management in 84.2% of
group A patients and in 85.7% of group B patients: 16 patients were scheduled for
urgent transplantation, 2 underwent surgical revision of the driveline, 7
required prolonged antibiotic therapy, and 3 underwent colonoscopy. CONCLUSIONS:
This single-center experience highlights the diagnostic value of PET/CT in
detecting the localization and internal extension of infection to internal VAD
components. Moreover, this information notably influences the therapeutic
management.
PMID- 26433522
TI - Hybrid Procedure for Neonates With Hypoplastic Left Heart Syndrome at High-Risk
for Norwood: Midterm Outcomes.
AB - BACKGROUND: Hybrid procedure offers patients with severe congenital heart disease
an alternative initial procedure to conventional surgical reconstruction. We
report the midterm outcomes of a cohort of neonates who had a hybrid procedure
for variants of hypoplastic left heart syndrome because they were at high risk
for the Norwood procedure. METHODS: Between December 2005 and January 2013, 41
neonates underwent bilateral pulmonary artery banding followed by ductal stenting
by means of a sternotomy at a median age of 6 days (range, 2 to 18 days) and
weight of 2.6 kg (range, 1.5 to 3.7 kg). Thirty-five patients had hypoplastic
left heart syndrome, and 6 patients had critical aortic stenosis with hypoplastic
left ventricle. Primary indications for the hybrid procedure were low birth
weight in 17 patients, hypoplastic left ventricle with the possibility of later
biventricular repair in 6 patients, intact or near-intact atrial septum in 5
patients, and poor patient condition in 13 patients. Echocardiographic,
angiographic, operative, and clinical data were reviewed. Outcomes were
summarized with descriptive statistics and risk factors for mortality identified.
RESULTS: All but 6 patients had an antenatal diagnosis, and 24 patients were from
other congenital cardiac centers. Nine patients had perioperative balloon aortic
valvuloplasty, 1 patient had fetal balloon aortic valvuloplasty, and 17 patients
had intervention to their atrial septum (41.4%). There were 9 inpatient deaths
(21.9%) and 4 interstage deaths (9.8%) after the hybrid procedure. Twenty-eight
patients subsequently underwent either the Norwood procedure (11 patients),
combined stage I and II (14 patients), or biventricular repair (3 patients). No
patient had heart transplantation. Among the patients who had combined stage I
and II as a second procedure after the hybrid procedure, there were 2 early
deaths, 1 late death before the Fontan, and 1 late death after the Fontan
completion after combined stage I and II. All patients who had subsequent Norwood
procedure were midterm survivors. Three of the 4 patients who had biventricular
repair were midterm survivors. Overall survival was 56.1% at a median follow-up
of 32.0 months. By univariate analysis, patient factors, intact or near-intact
atrial septum, and aortic atresia were associated with nonsurvival. CONCLUSIONS:
Hybrid procedure as an alternative to the Norwood procedure offers good midterm
survival in patients deemed at high risk for neonatal reconstruction.
PMID- 26433524
TI - Allergens in modern society: Updated catalogs and future prospects.
PMID- 26433523
TI - Transcatheter or Surgical Aortic Valve Replacement in Patients With Prior
Coronary Artery Bypass Grafting.
AB - BACKGROUND: Transcatheter aortic valve replacement (TAVR) and surgical aortic
valve replacement (SAVR) are treatment options for aortic stenosis in patients
with prior coronary artery bypass graft surgery. We assessed the major clinical
outcomes of such patients enrolled in the CoreValve High Risk (CHR) study.
METHODS: Of the 795 CHR study patients, 226 had prior coronary artery bypass
graft surgery; 115 underwent TAVR and 111 underwent SAVR. The primary endpoint
was a comparison of all-cause mortality at 1 year. Important secondary clinical
endpoints were assessed. RESULTS: At 1 year, all-cause mortality was 9.6% for
TAVR versus 18.1% for SAVR (p = 0.06); cardiovascular mortality was 7.0% for TAVR
versus 13.8% for SAVR (p = 0.09). A combination of The Society of Thoracic
Surgeons risk score greater than 7 and age greater than 80 years was a
significant predictor of mortality, with TAVR demonstrating a survival advantage
(p = 0.03). No differences were seen for stroke. The SAVR group had longer
intensive care unit and hospital stays, increased incidence of acute kidney
injury, life-threatening or disabling bleeding, and major adverse cardiac and
cerebrovascular events (p < 0.05). Pacemaker implantation and paravalvular
regurgitation were greater with TAVR at all timepoints. CONCLUSIONS: For patients
with prior coronary artery bypass graft surgery and aortic stenosis, TAVR offers
a significant morbidity advantage and a strong trend toward improved survival
over SAVR at 1 year.
PMID- 26433526
TI - Hierarchy and molecular properties of house dust mite allergens.
AB - The allergenic load of house dust mite allergy is largely constituted by a few
proteins with a hierarchical pattern of allergenicity. The serodominant
specificities are the group 1&2 and the group 23 faecal allergens. The collective
IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation
better than HDM extracts although discrepancies have been found in regions with
complex acarofauna suggesting a need to investigate the specificity with allergen
components. The group 4, 5, 7&21 allergens that each induce responses in about
40% of subjects are mid-tier allergens accounting for most of the remaining IgE
binding. Their titres are proportional to the concomitant responses to Der p1&2.
Group 2 allergen variants have different antibody binding. Body proteins only
occasionally induce sensitisation although a higher prevalence of binding by
atopic dermatitis patients provides a new avenue of research. A broad spectrum of
IgE binding has been associated with diverse symptoms but not with the severity
of asthma which is associated with low IgG antibody. Some allergens such as the
group 14 large lipid binding proteins and the recently described proteins Der f
24-33, need further investigation but with the cognoscence that other denominated
allergens have been found to be minor sensitisers by comparative quantitative
analyses. Scabies is a confounder for diagnosis with extracts, inducing cross
reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity
to Der p 10 a minor HDM allergen. The HDM genome sequence can now be used to
verify allelic and paralogous variations.
PMID- 26433527
TI - Spectrum of allergens for Japanese cedar pollinosis and impact of component
resolved diagnosis on allergen-specific immunotherapy.
AB - The high prevalence of Japanese cedar pollinosis in Japan is associated with a
negative impact on the quality of life of patients, as well as significant loss
of productivity among the workforce in early spring, thus representing a serious
social problem. Furthermore, the prevalence is increasing, and has risen by more
than 10% in this decade. Cry j 1 and Cry j 2 were identified as the major
allergens in Japanese cedar pollen (JCP), and in 2004, the existence of other
major and minor allergens were revealed by a combination of two-dimensional
electrophoresis and immunoblotting analysis. Allergenome analysis identified a
chitinase, a lipid transfer protein, a serine protease, and an aspartic protease
as novel IgE-reactive allergens in patients with JCP allergy. Thaumatin-like
protein (Cry j 3) was shown to be homologous to Jun a 3, a major allergen from
mountain cedar pollen. Isoflavone reductase-like protein was also characterized
in a study of a JCP cDNA library. The characterization of component allergens is
required to clarify the sensitizer or cross-reactive elicitor allergens for
component-resolved diagnosis (CRD). Increasing evidence from numerous clinical
trials indicates that CRD can be used to design effective allergen-specific
immunotherapy. In this review, we summarize the eight characterized JCP allergens
and discuss the impact of CRD and characterization of novel allergens on allergen
specific immunotherapy.
PMID- 26433525
TI - Allergens, sources, particles, and molecules: Why do we make IgE responses?
AB - Allergens are foreign proteins or glycoproteins that are the target of IgE
antibody responses in humans. The relationship between subsequent exposure and
the allergic symptoms is often or usually obvious; however, there is increasing
evidence that in asthma, atopic dermatitis and some forms of food allergy the
induction of symptoms is delayed or chronic. The primary exposure to inhaled
allergens is to the particles, which are capable of carrying allergens in the
air. Thus, the response reflects not only the properties of the proteins, but
also the biological properties of the other constituents of the particle. This is
best understood in relation to the mite fecal particles in which the contents
include many different immunologically active substances. Allergic disease first
became a major problem over 100 years ago, and for many years sensitization to
pollens was the dominant form of these diseases. The rise in pediatric asthma
correlates best with the move of children indoors, which started in 1960 and was
primarily driven by indoor entertainment for children. While the causes of the
increase are not simple they include both a major increase in sensitization to
indoor allergens and the complex consequences of inactivity. Most recently, there
has also been an increase in food allergy. Understanding this has required a
reappraisal of the importance of the skin as a route for sensitization. Overall,
understanding allergic diseases requires knowing about the sources, the particles
and the routes of exposure as well as the properties of the individual allergens.
PMID- 26433528
TI - Sensitization to fungal allergens: Resolved and unresolved issues.
AB - Exposure and sensitization to fungal allergens can promote the development and
worsening of allergic diseases. Although numerous species of fungi have been
associated with allergic diseases in the literature, the significance of fungi
from the genera Alternaria, Cladosporium, Penicillium, Aspergillus, and
Malassezia has been well documented. However, it should be emphasized that the
contribution of different fungal allergens to allergic diseases is not identical,
but species-specific. Alternaria and Cladosporium species are considered to be
important outdoor allergens, and sensitization and exposure to species of these
genera is related to the development of asthma and rhinitis, as well as epidemics
of asthma exacerbation, including life-threatening asthma exacerbation. In
contrast, xerophilic species of Penicillium and Aspergillus, excluding
Aspergillus fumigatus, are implicated in allergic diseases as indoor allergens.
A. fumigatus has a high capacity to colonize the bronchial tract of asthmatic
patients, causing severe persistent asthma and low lung function, and sometimes
leading to allergic bronchopulmonary aspergillosis. Malassezia are common
commensals of healthy skin, although they are also associated with atopic
dermatitis, especially on the head and neck, but not with respiratory allergies.
Despite its importance in the management of allergic diseases, precise
recognition of species-specific IgE sensitization to fungal allergens is often
challenging because the majority of fungal extracts exhibit broad cross
reactivity with taxonomically unrelated fungi. Recent progress in gene technology
has contributed to the identification of specific and cross-reactive allergen
components from different fungal sources. However, data demonstrating the
clinical relevance of IgE reactivity to these allergen components are still
insufficient.
PMID- 26433529
TI - Common food allergens and their IgE-binding epitopes.
AB - Food allergy is an adverse immune response to certain kinds of food. Although any
food can cause allergic reactions, chicken egg, cow's milk, wheat, shellfish,
fruit, and buckwheat account for 75% of food allergies in Japan. Allergen
specific immunoglobulin E (IgE) antibodies play a pivotal role in the development
of food allergy. Recent advances in molecular biological techniques have enabled
the efficient analysis of food allergens. As a result, many food allergens have
been identified, and their molecular structure and IgE-binding epitopes have also
been identified. Studies of allergens have demonstrated that IgE antibodies
specific to allergen components and/or the peptide epitopes are good indicators
for the identification of patients with food allergy, prediction of clinical
severity and development of tolerance. In this review, we summarize our current
knowledge regarding the allergens and IgE epitopes in the well-researched
allergies to chicken egg, cow's milk, wheat, shrimp, and peanut.
PMID- 26433530
TI - Indicators of violence and asthma: An ecological study.
AB - BACKGROUND: Global studies on asthma point to socioeconomic status as one of the
main variables in terms of prevalence and disease severity in various parts of
the world. Social factors related to community violence have been linked to
higher incidence of asthma in the current studies. This study investigates the
relationship between indicators of both community violence and development and
hospital admissions due to asthma. METHODS: This was an analytical ecological
study of multiple groups, using public databases with information up until 2006.
All Brazilian municipalities with more than 100,000 inhabitants were considered
as units of analysis. The main index used as socioeconomic indicator was the
FIRJAN Index of Municipal Development (FIMD). The Index of Youth Vulnerability to
Violence (IYVV) was used as indicators of community violence. The rate of
admissions due to asthma was used as the outcome. Pearson's correlation was used
for multivariate analyses. The coefficient of determination (R(2)) was calculated
and the simple linear regression model adjusted for significant correlations.
RESULTS: There was an inverse correlation between asthma admissions and FIMD (r =
-0.354, p < 0.001), with statistical significance for all dimensions of the
index. Admissions due to asthma were associated with the IYVV (r = 0.240, p <
0.001) and its component related to school attendance and employment (r = 0.315,
p < 0.001), homicides (r = 0.112, p = 0.034), and poverty (r = 0.303, p < 0.001).
CONCLUSIONS: There was a direct correlation between indicators of violence and
rates of admission due asthma, and an inverse correlation with indicators of
development. These results suggest that social detriment can act as a risk factor
for hospital admissions due to asthma.
PMID- 26433531
TI - Expression of CysLT2 receptors in asthma lung, and their possible role in
bronchoconstriction.
AB - BACKGROUND: The expression and functional role of CysLT2 receptors in asthma have
not been clarified. In this study, we evaluated CysLT2 receptors expression, and
effects of CysLT2-and CysLT1/2-receptor antagonists on antigen-induced
bronchoconstriction using isolated lung tissues from both asthma and non-asthma
subjects. METHODS: CysLT1 and CysLT2 receptors expression in asthma and non
asthma lung tissue preparations was examined in immunohistochemistry experiments,
and their functional roles in antigen-induced bronchoconstriction were assessed
using ONO-6950, a dual CysLT1/2-receptor antagonist, montelukast, a CysLT1
receptor antagonist, and BayCysLT2RA, a CysLT2 receptor-specific antagonist.
RESULTS: CysLT1 receptors were expressed on the bronchial smooth muscle and
epithelium, and on alveolar leukocytes in 5 in 5 non-asthma subjects and 2 in 2
asthma subjects. On the other hand, although degrees of CysLT2 receptors
expression were variable among the 5 non-asthma subjects, the expression in the
asthma lung was detected on bronchial smooth muscle, epithelium and alveolar
leukocytes in 2 in 2 asthma subjects. In the non-asthma specimens, antagonism of
CysLT2 receptors did not affect antigen-induced bronchial contractions, even
after pretreatment with the CysLT1-receptor specific antagonist, montelukast.
However, in the bronchus isolated from one of the 2 asthma subjects, antagonism
of CysLT2 receptors suppressed contractions, and dual antagonism of CysLT1 and
CysLT2 receptors resulted in additive inhibitory effect on anaphylactic
contractions. CONCLUSIONS: CysLT2 receptors were expressed in lung specimens
isolated from asthma subjects. Activation of CysLT2 receptors may contribute to
antigen-induced bronchoconstriction in certain asthma population.
PMID- 26433532
TI - Elevated exhaled nitric oxide in anaphylaxis with respiratory symptoms.
AB - BACKGROUND: Anaphylaxis is a serious type I allergic reaction that occurs
suddenly and can result in death, but it is sometimes difficult to differentiate
from other diseases, and physicians must rely on symptoms alone for its
diagnosis. Meanwhile, fractional exhaled nitric oxide (FeNO) concentration, used
in assessing airway inflammation in bronchial asthma, is known to be affected by
atopic disposition. The possible role of FeNO measurements was evaluated in
patients with anaphylaxis. METHODS: FeNO was measured in 52 adult patients (17-78
years old, median age 41.5 years) in whom anaphylaxis occurred. These
measurements were made within 24 h after onset and after about one month when the
patients were symptom-free. In some of these patients, FeNO was measured a third
time, two months or more after onset. RESULTS: The FeNO level in the 52 patients
was not significantly different in measurement made within 24 h of onset of
anaphylaxis and after one month. However, excluding 9 patients who also had
asthma history, the FeNO level in the remaining 43 patients decreased
significantly from within 24 h of onset (36.7 +/- 27.5 ppb) to one month later
(28.8 +/- 19.5 ppb). Of these 43 patients, this phenomenon was evident in a group
that had respiratory symptoms (31 patients), but it was not seen in a group that
did not have respiratory symptoms (12 patients). CONCLUSIONS: Elevation of FeNO
was related to respiratory symptoms observed in anaphylactic patients without
asthma. Although the mechanism of increased FeNO level is unclear, its usefulness
for diagnosis of anaphylaxis must be examined in prospective studies.
PMID- 26433533
TI - Omalizumab in Japanese children with severe allergic asthma uncontrolled with
standard therapy.
AB - BACKGROUND: Omalizumab has demonstrated clinical benefits in children with
moderate to severe allergic asthma. However, no studies have been performed in
Japanese asthmatic children. The aim of this study was to evaluate the efficacy
including free IgE suppression and safety of omalizumab in Japanese children with
severe allergic asthma. The primary objective was to examine whether omalizumab
decreases serum free IgE levels to less than 25 ng/ml (target level of
suppression). METHODS: Thirty-eight Japanese children (6-15 years) with
uncontrolled severe allergic asthma despite inhaled corticosteroids (>200 MUg/day
fluticasone propionate or equivalent) and two or more controller therapies
received add-on treatment with omalizumab in a 24-week, multicenter,
uncontrolled, open-label study. RESULTS: The geometric mean serum free IgE level
at 24 weeks was 15.6 ng/mL. Compared with baseline, total asthma symptom scores,
daily activity scores and nocturnal sleep scores at 24 weeks were significantly
improved. The rates of asthma exacerbation and hospitalization due to asthma were
reduced by 69.2% and 78.2%, respectively (p < 0.001), versus baseline. Quality-of
life scores were also significantly improved (p < 0.001). In addition, 11 (28.9%)
patients reduced the dose of any asthma controller medications. Thirty-six
(94.7%) patients experienced at least one adverse event during the treatment
period. All adverse events were mild or moderate in severity and no new safety
concerns were detected. No patients discontinued the study. CONCLUSIONS: In
Japanese children with severe allergic asthma, omalizumab decreased free IgE
levels to less than 25 ng/mL. Omalizumab improved asthma control and was well
tolerated, as well.
PMID- 26433535
TI - A case of fixed drug eruption caused by loxoprofen sodium hydrate.
PMID- 26433534
TI - Caregiver treatment satisfaction is improved together with children's asthma
control: Prospective study for budesonide monotherapy in school-aged children
with uncontrolled asthma symptoms.
AB - BACKGROUND: If asthmatic children cannot obtain sufficient control of their
disease, not only do they suffer from asthma symptoms, but the daily life
activities of their caregivers are also disrupted. We investigated the
effectiveness of an inhaled corticosteroid (ICS) for symptom control in
previously ICS-untreated school-aged asthmatic children as well as caregiver
treatment satisfaction (CTS). METHODS: A multicenter, open-label, single-arm
study on 12-week ICS (budesonide Turbuhaler(r)) monotherapy was undertaken in
subjects aged 5-15 years with bronchial asthma not treated with ICS during the
previous 3 months. At 0, 4, 8, and 12 weeks after start of ICS administration,
Japanese Pediatric Asthma Control Program (JPAC) scores, and CTS scores were
summated and lung function measured. At weeks 0 and 12, questionnaires on
caregiver anxiety were also assessed. RESULTS: Seventy-five patients were
enrolled, and 69 assessed. Ninety percent of subjects had been treated with
asthma controller medication except ICS before study enrollment. JPAC score and
CTS score were improved significantly at weeks 4, 8, and 12 (p < 0.001). With
regard to CTS, more than half of caregivers showed a perfect score at weeks 8 and
12. There was a significant correlation between JPAC score and CTS score. Lung
function and caregiver anxiety were also improved, and good compliance with
treatment was observed during the intervention. CONCLUSIONS: If treating ICS
untreated school-aged asthmatic children with uncontrolled symptoms, ICS
monotherapy can improve CTS along with improving asthma control.
PMID- 26433536
TI - Drugs causing severe ocular surface involvements in Japanese patients with
Stevens-Johnson syndrome/toxic epidermal necrolysis.
PMID- 26433537
TI - Atopic dermatitis exacerbated with ustekinumab in a psoriatic patient with
childhood history of atopy.
PMID- 26433538
TI - Par j 2 IgE measurement for distinguishing between sensitization and allergy.
PMID- 26433539
TI - A case of an anaphylactic reaction due to oats in granola.
PMID- 26433540
TI - Usefulness of rapid measurement of serum thymus and activation-regulated
chemokine level in diagnosing drug-induced hypersensitivity syndrome.
PMID- 26433541
TI - Comparison of the aerosol velocity of Respimat(r) soft mist inhaler and seven
pressurized metered dose inhalers.
PMID- 26433542
TI - A case of oral allergy syndrome due to star fruit sensitized from atopic hands.
PMID- 26433543
TI - Diagnosis of IgE-mediated hypersensitivity to sesame seeds supplemented with
lipid body proteins.
PMID- 26433545
TI - Acute parkinsonism in alcohol withdrawal: A case report.
PMID- 26433546
TI - A randomized phase II study of Xilonix, a targeted therapy against interleukin
1alpha, for the prevention of superficial femoral artery restenosis after
percutaneous revascularization.
AB - OBJECTIVE: The purpose of this study was to evaluate an anti-interleukin 1alpha
antibody for its ability to reduce acute postprocedural inflammation, thereby
reducing neointimal hyperplasia and restenosis after superficial femoral artery
(SFA) angioplasty. Restenosis of the SFA after endovascular intervention is a
common problem leading to 1-year primary patency as low as 40%. These failures
are primarily due to the development of neointimal hyperplasia, resulting from
arterial wall inflammation. METHODS: This was a randomized, phase II trial
examining SFA restenosis in patients after percutaneous revascularization.
Randomization occurred after successful revascularization, and patients were
assigned to either the standard of care arm or the Xilonix (XBiotech USA, Inc,
Austin, Tex) plus standard of care arm (N = 43). Xilonix was administered
immediately after revascularization, every 2 weeks intravenously for four doses,
and monthly subcutaneously until month 12. The major efficacy end points were
target vessel event-free survival and incidence of major adverse cardiovascular
events (MACEs). RESULTS: At 12 months of follow-up, MACE (43% vs 36%; P = .76)
and target vessel restenosis (24% vs 27%; log-rank, P = .79) rates were not
significantly different between the groups. At 3-month follow-up, which covers
the intravenous dosing period, a trend toward lower incidence of restenosis (0 of
22 [0%] vs 2 of 21 [10%]; P = .14) and MACE (2 of 22 [9%] vs 5 of 21 [24%]; P =
.22) was observed in the Xilonix cohort. Adverse events were equally distributed
in both arms. CONCLUSIONS: Xilonix was well tolerated. Observed tendency to
improved vessel patency with intravenous dosing suggests Xilonix could
potentially represent a safe and effective therapeutic approach to preserving
vessel patency.
PMID- 26433544
TI - Information in pallidal neurons increases with parkinsonian severity.
AB - INTRODUCTION: The motor symptoms of Parkinson's disease (PD) present with
pathological neuronal activity in the basal ganglia. Although neuronal firing
rate changes in the globus pallidus internus (GPi) and externus (GPe) are
reported to underlie the development of PD motor signs, firing rates change
inconsistently, vary confoundingly with some therapies, and are poor indicators
of symptom severity. METHODS: We explored the relationship between parkinsonian
symptom severity and the effectiveness with which pallidal neurons transmit
information. We quantify neuronal entropy and information - alternatives to
firing rate and correlations respectively - in and between GPe and GPi neurons
using a progressive, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, non-human
primate model of PD. RESULTS: Neuronal entropy and symptom severity were not
linearly correlated: in both pallidal segments, entropy increased from naive to
moderate parkinsonism, but decreased with further progression to the severely
parkinsonian condition. In contrast, information transmitted from GPe to GPi
increased consistently with symptom severity. Furthermore, antidromic information
from GPi to GPe increased substantially with symptom severity. Together, these
findings suggest that as parkinsonian severity increases, more and more
information enters GPe and GPi from common sources, diminishing the relative
importance of the orthodromic GPe to GPi connection. CONCLUSIONS: With
parkinsonian progression, the direct and indirect pathways lose their
independence and start to convey redundant information. We hypothesize that a
loss of parallel processing impairs the ability of the network to select and
implement motor commands, thus promoting the hypokinetic symptoms of PD.
PMID- 26433547
TI - A meta-analysis of water quality and aquatic macrophyte responses in 18 lakes
treated with lanthanum modified bentonite (Phoslock((r))).
AB - Lanthanum (La) modified bentonite is being increasingly used as a geo-engineering
tool for the control of phosphorus (P) release from lake bed sediments to
overlying waters. However, little is known about its effectiveness in controlling
P across a wide range of lake conditions or of its potential to promote rapid
ecological recovery. We combined data from 18 treated lakes to examine the lake
population responses in the 24 months following La-bentonite application (range
of La-bentonite loads: 1.4-6.7 tonnes ha(-1)) in concentrations of surface water
total phosphorus (TP; data available from 15 lakes), soluble reactive phosphorus
(SRP; 14 lakes), and chlorophyll a (15 lakes), and in Secchi disk depths (15
lakes), aquatic macrophyte species numbers (6 lakes) and aquatic macrophyte
maximum colonisation depths (4 lakes) across the treated lakes. Data availability
varied across the lakes and variables, and in general monitoring was more
frequent closer to the application dates. Median annual TP concentrations
decreased significantly across the lakes, following the La-bentonite applications
(from 0.08 mg L(-1) in the 24 months pre-application to 0.03 mg L(-1) in the 24
months post-application), particularly in autumn (0.08 mg L(-1) to 0.03 mg L(-1))
and winter (0.08 mg L(-1) to 0.02 mg L(-1)). Significant decreases in SRP
concentrations over annual (0.019 mg L(-1) to 0.005 mg L(-1)), summer (0.018 mg
L(-1) to 0.004 mg L(-1)), autumn (0.019 mg L(-1) to 0.005 mg L(-1)) and winter
(0.033 mg L(-1) to 0.005 mg L(-1)) periods were also reported. P concentrations
following La-bentonite application varied across the lakes and were correlated
positively with dissolved organic carbon concentrations. Relatively weak, but
significant responses were reported for summer chlorophyll a concentrations and
Secchi disk depths following La-bentonite applications, the 75th percentile
values decreasing from 119 MUg L(-1) to 74 MUg L(-1) and increasing from 398 cm
to 506 cm, respectively. Aquatic macrophyte species numbers and maximum
colonisation depths increased following La-bentonite application from a median of
5.5 species to 7.0 species and a median of 1.8 m to 2.5 m, respectively. The
aquatic macrophyte responses varied significantly between lakes. La-bentonite
application resulted in a general improvement in water quality leading to an
improvement in the aquatic macrophyte community within 24 months. However,
because, the responses were highly site-specific, we stress the need for
comprehensive pre- and post-application assessments of processes driving
ecological structure and function in candidate lakes to inform future use of this
and similar products.
PMID- 26433548
TI - Progress and Infrastructure for Improved Patient Outcomes of the National Cancer
Institute Network Groups.
PMID- 26433549
TI - Involving Advocates in Cancer Research.
AB - Advocates can play an important role in cancer research. In 2010, the National
Cancer Institute (NCI) Advocate in Research Working Group (ARWG) defined a
"research advocate" as an individual who brings and can convey a nonscientific
viewpoint to the research process and can communicate a collective patient
perspective through knowledge of multiple disease experiences. Experiences cited
in this review are related to publically funded research. They, exemplify
challenges and successes of advocate engagement and involvement in the cancer
research process.
PMID- 26433550
TI - Cooperative Group Trials in the Community Setting.
AB - Over the last 40 years the National Cancer Institute (NCI) has created a vibrant
public-private partnership for the implementation of NCI-sponsored cooperative
group (Network) clinical trials throughout the United States and Canada. Over
these four decades, the cancer clinical trials process has become more complex
more precise and more resource intensive. During this same time period, financial
resources to support the NCI community research initiative have become more
constrained. The newest manifestation of NCI-sponsored community based cancer
clinical trial research, known as the National Community Oncology Research
Program (NCORP) began initial operation August 1, 2014. We describe several key
strategies that community sites may use to not only be successful but to thrive
in this new financially austere research environment.
PMID- 26433553
TI - The Master Protocol Concept.
AB - During the past decade, biomedical technologies have undergone an explosive
evolution-from the publication of the first complete human genome in 2003, after
more than a decade of effort and at a cost of hundreds of millions of dollars-to
the present time, where a complete genomic sequence can be available in less than
a day and at a small fraction of the cost of the original sequence. The
widespread availability of next-generation genomic sequencing has opened the door
to the development of precision oncology. The need to test multiple new targeted
agents both alone and in combination with other targeted therapies, as well as
classic cytotoxic agents, demands the development of novel therapeutic platforms
(particularly Master Protocols) capable of efficiently and effectively testing
multiple targeted agents or targeted therapeutic strategies in relatively small
patient subpopulations. Here, we describe the Master Protocol concept, with a
focus on the expected gains and complexities of the use of this design. An
overview of Master Protocols currently active or in development is provided along
with a more extensive discussion of the Lung Master Protocol (Lung-MAP study).
PMID- 26433552
TI - Genetic Testing and Tissue Banking for Personalized Oncology: Analytical and
Institutional Factors.
AB - Personalized oncology, or more aptly precision oncogenomics, refers to the
identification and implementation of clinically actionable targets tailored to an
individual patient's cancer genomic information. Banking of human tissue and
other biospecimens establishes a framework to extract and collect the data
essential to our understanding of disease pathogenesis and treatment. Cancer
cooperative groups in the United States have led the way in establishing robust
biospecimen collection mechanisms to facilitate translational research, and
combined with technological advances in molecular testing, tissue banking has
expanded from its traditional base in academic research and is assuming an
increasingly pivotal role in directing the clinical care of cancer patients.
Comprehensive screening of tumors by DNA sequencing and the ability to mine and
interpret these large data sets from well-organized tissue banks have defined
molecular subtypes of cancer. Such stratification by genomic criteria has
revolutionized our perspectives on cancer diagnosis and treatment, offering
insight into prognosis, progression, and susceptibility or resistance to known
therapeutic agents. In turn, this has enabled clinicians to offer treatments
tailored to patients that can greatly improve their chances of survival. Unique
challenges and opportunities accompany the rapidly evolving interplay between
tissue banking and genomic sequencing, and are the driving forces underlying the
revolution in precision medicine. Molecular testing and precision medicine
clinical trials are now becoming the major thrust behind the cooperative groups'
clinical research efforts.
PMID- 26433554
TI - The National Clinical Trials Network: Conducting Successful Clinical Trials of
New Therapies for Rare Cancers.
AB - Rare cancers account for 27% of neoplasms diagnosed each year, and 25% of cancer
related deaths in the United States. However, rare cancers show some of the
highest response rates to targeted therapies, probably due to identification of
oncogenic drivers with little interpatient variability. Although the low
incidence of rare cancers makes large-scale randomized trials involving single
histologies difficult to perform, drugs have been successfully developed in rare
cancers using clinical trial designs that combine microscopic histologies. Such
trials are being pursued within the National Clinical Trials Network (NCTN),
which possesses unique qualifications to perform widespread molecular screening
of tumors for patient enrollment onto therapeutic clinical trials. When larger
clinical trials are needed to determine optimum treatment strategies in rare
cancers, the NCTN's broad reach in North America and internationally, and their
ability to partner with both United States-based and international research
organizations, can make these challenging studies feasible.
PMID- 26433555
TI - Enhancing Adolescent and Young Adult Oncology Research Within the National
Clinical Trials Network: Rationale, Progress, and Emerging Strategies.
AB - Adolescent and Young Adult Oncology (AYAO, including patients 15-39 years of age)
is an emerging discipline in the field of cancer treatment and research. Poorer
survival outcomes for this population and characteristic age-related challenges
in care have called attention to the need for increased AYAO research. This
chapter outlines pressing questions and reviews recent progress in AYAO research
within the current organizational structure of the federal clinical trials
enterprise, emphasizing how the United States National Cancer Institute's
National Clinical Trials Network (NCTN) has created novel opportunities for
collaborative AYAO research among the pediatric and adult NCTN groups. Potential
strategies for expanding AYAO research, both within the NCTN and with other
partners in the federal and advocacy domains are identified.
PMID- 26433557
TI - Social Media and Oncology: The Past, Present, and Future of Electronic
Communication Between Physician and Patient.
AB - The relationship between patient and physician is in flux with the advent of
electronic media that are advancing and enhancing communication. We perform a
retrospective, current, and forward-looking examination of the technologies by
which information is exchanged within the healthcare community. The evolution
from e-mail and listservs to blogs and the modern social networks is described,
with emphasis on the advantages and pitfalls of each medium, especially in regard
to maintaining the standards of privacy and professionalism to which doctors are
held accountable. We support the use of contemporary platforms like Twitter and
Facebook for physicians to establish themselves as trustworthy online sources of
medical knowledge, and anticipate ongoing collaboration between researchers,
patients, and their advocates in trial design and accrual.
PMID- 26433558
TI - A 46-Year-Old Asian Woman With Liver Mass.
PMID- 26433559
TI - Analyzing IVF laboratory error rates: highlight or hide?
PMID- 26433551
TI - The Globalization of Cooperative Groups.
AB - The National Cancer Institute (NCI)-supported adult cooperative oncology research
groups (now officially Network groups) have a longstanding history of
participating in international collaborations throughout the world. Most
frequently, the US-based cooperative groups work reciprocally with the Canadian
national adult cancer clinical trial group, NCIC CTG (previously the National
Cancer Institute of Canada Clinical Trials Group). Thus, Canada is the largest
contributor to cooperative groups based in the United States, and vice versa.
Although international collaborations have many benefits, they are most
frequently utilized to enhance patient accrual to large phase III trials
originating in the United States or Canada. Within the cooperative group setting,
adequate attention has not been given to the study of cancers that are unique to
countries outside the United States and Canada, such as those frequently
associated with infections in Latin America, Asia, and Africa. Global
collaborations are limited by a number of barriers, some of which are unique to
the countries involved, while others are related to financial support and to US
policies that restrict drug distribution outside the United States. This article
serves to detail the cooperative group experience in international research and
describe how international collaboration in cancer clinical trials is a promising
and important area that requires greater consideration in the future.
PMID- 26433556
TI - Ongoing Use of Data and Specimens From National Cancer Institute-Sponsored Cancer
Prevention Clinical Trials in the Community Clinical Oncology Program.
AB - Large cancer prevention trials provide opportunities to collect a wide array of
data and biospecimens at study entry and longitudinally, for a healthy, aging
population without cancer. This provides an opportunity to use pre-diagnostic
data and specimens to evaluate hypotheses about the initial development of
cancer. We report on strides made by, and future possibilities for, the use of
accessible biorepositories developed from precisely annotated samples obtained
through large-scale National Cancer Institute (NCI)-sponsored cancer prevention
clinical trials conducted by the NCI Cooperative Groups. These large cancer
prevention studies, which have enrolled more than 80,000 volunteers, continue to
contribute to our understanding of cancer development more than 10 years after
they were closed.
PMID- 26433560
TI - Extracellular vesicle-derived protein from Bifidobacterium longum alleviates food
allergy through mast cell suppression.
AB - BACKGROUND: The incidence of food allergies has increased dramatically during the
last decade. Recently, probiotics have been studied for the prevention and
treatment of allergic disease. OBJECTIVE: We examined whether Bifidobacterium
longum KACC 91563 and Enterococcus faecalis KACC 91532 have the capacity to
suppress food allergies. METHODS: B longum KACC 91563 and E faecalis KACC 91532
were administered to BALB/c wild-type mice, in which food allergy was induced by
using ovalbumin and alum. Food allergy symptoms and various immune responses were
assessed. RESULTS: B longum KACC 91563, but not E faecalis KACC 91532, alleviated
food allergy symptoms. Extracellular vesicles of B longum KACC 91563 bound
specifically to mast cells and induced apoptosis without affecting T-cell immune
responses. Furthermore, injection of family 5 extracellular solute-binding
protein, a main component of extracellular vesicles, into mice markedly reduced
the occurrence of diarrhea in a mouse food allergy model. CONCLUSION: B longum
KACC 91563 induces apoptosis of mast cells specifically and alleviates food
allergy symptoms. Accordingly, B longum KACC 91563 and family 5 extracellular
solute-binding protein exhibit potential as therapeutic approaches for food
allergies.
PMID- 26433561
TI - Wheel running exercise attenuates vulnerability to self-administer nicotine in
rats.
AB - BACKGROUND: Preventing or postponing tobacco use initiation could greatly reduce
the number of tobacco-related deaths. While evidence suggests that exercise is a
promising treatment for tobacco addiction, it is not clear whether exercise could
prevent initial vulnerability to tobacco use. Thus, using an animal model, we
examined whether exercise attenuates vulnerability to the use and reinforcing
effects of nicotine, the primary addictive chemical in tobacco. METHODS: Initial
vulnerability was assessed using an acquisition procedure wherein exercising
(unlocked running wheel, n=10) and sedentary (locked or no wheel, n=12) male
adolescent rats had access to nicotine infusions (0.01-mg/kg) during daily 21.5-h
sessions beginning on postnatal day 30. Exercise/sedentary sessions (2-h/day)
were conducted prior to each of the acquisition sessions. The effects of exercise
on nicotine's reinforcing effects were further assessed in separate groups of
exercising (unlocked wheel, n=7) and sedentary (no wheel, n=5) rats responding
for nicotine under a progressive-ratio schedule with exercise/sedentary sessions
(2-h/day) conducted before the daily progressive-ratio sessions. RESULTS: While
high rates of acquisition of nicotine self-administration were observed among
both groups of sedentary controls, acquisition was robustly attenuated in the
exercise group with only 20% of exercising rats meeting the acquisition criterion
within the 16-day testing period as compared to 67% of the sedentary controls.
Exercise also decreased progressive-ratio responding for nicotine as compared to
baseline and to sedentary controls. CONCLUSIONS: Exercise may effectively prevent
the initiation of nicotine use in adolescents by reducing the reinforcing effects
of nicotine.
PMID- 26433564
TI - Who receives cannabis use offers: A general population study of adolescents.
AB - BACKGROUND: Drug use is predicated on a combination of "willingness" and
"opportunity". That is, independent of any desire to use drugs, a drug use
opportunity is required; be it indirect (i.e., being in a drug-use setting) or
direct (i.e., receiving a direct drug offer). However, whether some youth are
more likely to encounter such direct drug use opportunities is not fully known.
AIMS: We examined whether certain characteristics placed adolescents at greater
risk for being offered cannabis, after accounting for a number of demographic-,
contextual-, interpersonal-, and personal-level risk factors. METHODS: We
utilized data from a Norwegian school survey (n=19,309) where the likelihood of
receiving cannabis offer in the past year was estimated using logistic regression
models. Substantive focus was on the individual and combined effects of personal
(i.e., delinquency) and interpersonal (i.e., cannabis-using close friend) risk
factors. Separate models were fit for middle- and high-school students. RESULTS:
Delinquency was a significant risk factor for receiving cannabis offers, as was a
cannabis-using best friend. In addition, peer cannabis use increased the risk of
cannabis offers mostly for adolescents on the lower delinquency spectrum, but
less so for highly delinquent adolescents. These interaction effects were
primarily driven by the middle-school cohort. CONCLUSIONS: Cannabis offers were
more likely to be extended to youth of certain high-risk profiles. Targeted
prevention strategies can therefore be extended to a general profile of younger
adolescents with externalizing problems and cannabis-using peers.
PMID- 26433563
TI - Categorical perception of emotional facial expressions in alcohol-dependence.
AB - BACKGROUND: Emotional deficits have been widely described in alcohol-dependence,
but several subtle and critical emotional decoding abilities remain to be
investigated. In particular, the ability of alcohol-dependent individuals to
process emotionally ambiguous facial stimuli, which are more frequent in everyday
life than full emotional facial expressions, remains poorly understood. The
present study used a categorical perception paradigm to evaluate the
identification of mixed emotional facial expressions among alcohol-dependent
participants. METHOD: Nineteen recently detoxified participants with alcohol
dependence and 19 healthy controls were presented with facial stimuli depicting
four emotional facial expressions (happy, angry, sad, and neutral), morphed along
continua between each possible pair of emotions. Participants had to indicate the
predominant emotion within the randomly presented facial stimuli. For each
emotional category, a logistic function that estimated the percentage of
identification according to the morph steps was adjusted for each participant's
data. RESULTS: While there was no significant group difference regarding the
response slope (p=0.502, etap(2)=0.014), the identification threshold was
significantly increased in alcohol-dependent participants compared to controls
(p=0.007, etap(2)=0.204), independently of the emotional category. CONCLUSIONS:
The categorical perception of emotional facial expression per se appeared
preserved in alcohol-dependence, but alcohol-dependent participants exhibited a
bias in emotional facial expression decoding characterized by a global under
identification. This study is the first to evidence a deficit of alcohol
dependent individuals in the processing of ambiguous emotional facial expressions
by using this emotional continuum paradigm measuring the categorical perception
effect.
PMID- 26433562
TI - Predictors of outcome from computer-based treatment for substance use disorders:
Results from a randomized clinical trial.
AB - BACKGROUND: Although empirical evidence for the effectiveness of technology
mediated interventions for substance use disorders is rapidly growing, the role
of baseline characteristics of patients in predicting treatment outcomes of a
technology-based therapy is largely unknown. METHOD: Participants were randomly
assigned to either standard methadone maintenance treatment or reduced standard
treatment combined with the computer-based therapeutic education system (TES). An
array of demographic and behavioral characteristics of participants (N=160) was
measured at baseline. Opioid abstinence and treatment retention were measured
weekly for a 52-week intervention period. Generalized linear model and Cox
regression were used to estimate the predictive roles of baseline characteristics
in predicting treatment outcomes. RESULTS: We found significant predictors of
opioid abstinence and treatment retention within and across conditions. Among 21
baseline characteristics of participants, employment status, anxiety, and
ambivalent attitudes toward substance use predicted better opioid abstinence in
the reduced-standard-plus-TES condition compared to standard treatment.
Participants who had used cocaine/crack in the past 30 days at baseline showed
lower dropout rates in standard treatment, whereas those who had not used
exhibited lower dropout rates in the reduced-standard-plus-TES condition.
CONCLUSIONS: This study is the first randomized controlled trial, evaluating over
a 12-month period, how various aspects of participant characteristics impact
outcomes for treatments that do or do not include technology-based therapy.
Compared to standard alone treatment, including TES as part of the care was
preferable for patients who were employed, highly anxious, and ambivalent about
substance use and did not produce worse outcomes for any subgroups of
participants.
PMID- 26433565
TI - An evaluation of the Public Health Responsibility Deal: Informants' experiences
and views of the development, implementation and achievements of a pledge-based,
public-private partnership to improve population health in England.
AB - OBJECTIVES: The Coalition Government's Public Health Responsibility Deal (RD) was
launched in England in 2011 as a public-private partnership designed to improve
public health in the areas of food, alcohol, health at work and physical
activity. As part of a larger evaluation, we explored informants' experiences and
views about the RD's development, implementation and achievements. METHODS: We
conducted 44 semi-structured interviews with 50 interviewees, purposively sampled
from: RD partners (businesses, public sector and non-governmental organisations);
individuals with formal roles in implementing the RD; and non-partners and former
partners. Data were analysed thematically: NVivo (10) software was employed to
manage the data. RESULTS: Key motivations underpinning participation were
corporate social responsibility and reputational enhancement. Being a partner
often involved making pledges related to work already underway or planned before
joining the RD, suggesting limited 'added value' from the RD, although some
pledge achievements (e.g., food reformulation) were described. Benefits included
access to government, while drawbacks included resource implications and the risk
of an 'uneven playing field' between partners and non-partners. CONCLUSIONS: To
ensure that voluntary agreements like the RD produce gains to public health that
would not otherwise have occurred, government needs to: increase participation
and compliance through incentives and sanctions, including those affecting
organisational reputation; create greater visibility of voluntary agreements; and
increase scrutiny and monitoring of partners' pledge activities.
PMID- 26433566
TI - Development of a three-dimensional pre-vascularized scaffold-free contractile
cardiac patch for treating heart disease.
AB - BACKGROUND: The aim of our study was to develop a completely scaffold-free,
viable, contractile cardiac tissue capable of being grafted into the damaged
native heart. METHODS: Our technology is based on the fundamental characteristics
of the self-assembling nature of cells. We created contractile cardiac spheroids
by plating a mixture of rat neonatal ventricular cardiomyocytes, human dermal
fibroblasts, and human coronary microartery endothelial cells in ultralow
attachment plates. First, the optimal cell ratios for the 3 cell sources were
determined. Next, approximately 1 * 10(4) optimal spheroids were fused into a
patch-like construct, and the morphologic characteristics and mechanical
functions of these patches were evaluated. Finally, the cardiac patches were
grafted into the hearts of F344 nude rats, and histologic studies were performed
after transplantation. RESULTS: Synchronous beating of the cardiac patch was
confirmed electrophysiologically and mechanically. A micronetwork of endothelial
cells was also demonstrated in the construct, and the histologic study performed
5 days after transplantation showed the grafts to be viable, with functioning
microvascular structures inside the graft tissue. CONCLUSIONS: We consider the
application of our scaffold-free 3-dimensional tissue engineering technology to
cardiac regeneration therapy is feasible and expect that this technology will
become a promising tool for the treatment of end-stage heart failure.
PMID- 26433567
TI - Driver drowsiness detection based on non-intrusive metrics considering individual
specifics.
AB - OBJECTIVES: Drowsy driving is a serious highway safety problem. If drivers could
be warned before they became too drowsy to drive safely, some drowsiness-related
crashes could be prevented. The presentation of timely warnings, however, depends
on reliable detection. To date, the effectiveness of drowsiness detection methods
has been limited by their failure to consider individual differences. The present
study sought to develop a drowsiness detection model that accommodates the
varying individual effects of drowsiness on driving performance. METHODS:
Nineteen driving behavior variables and four eye feature variables were measured
as participants drove a fixed road course in a high fidelity motion-based driving
simulator after having worked an 8-h night shift. During the test, participants
were asked to report their drowsiness level using the Karolinska Sleepiness Scale
at the midpoint of each of the six rounds through the road course. A multilevel
ordered logit (MOL) model, an ordered logit model, and an artificial neural
network model were used to determine drowsiness. RESULTS: The MOL had the highest
drowsiness detection accuracy, which shows that consideration of individual
differences improves the models' ability to detect drowsiness. According to the
results, percentage of eyelid closure, average pupil diameter, standard deviation
of lateral position and steering wheel reversals was the most important of the 23
variables. CONCLUSION: The consideration of individual differences on a
drowsiness detection model would increase the accuracy of the model's detection
accuracy.
PMID- 26433568
TI - An extension of the theory of planned behavior to predict pedestrians' violating
crossing behavior using structural equation modeling.
AB - This paper aimed to examine pedestrians' self-reported violating crossing
behavior intentions by applying the theory of planned behavior (TPB). We studied
the behavior intentions regarding instrumental attitude, subjective norm,
perceived behavioral control, the three basic components of TPB, and extended the
theory by adding new factors including descriptive norm, perceived risk and
conformity tendency to evaluate their respective impacts on pedestrians' behavior
intentions. A questionnaire presented with a scenario that pedestrians crossed
the road violating the pedestrian lights at an intersection was designed, and the
survey was conducted in Dalian, China. Based on the 260 complete and valid
responses, reliability and validity of the data for each question was evaluated.
The data were then analyzed by using the structural equation modeling (SEM). The
results showed that people had a negative attitude toward the behavior of
violating road-crossing rules; they perceived social influences from their family
and friends; and they believed that this kind of risky behavior would potentially
harm them in a traffic accident. The results also showed that instrumental
attitude and subjective norm were significant in the basic TPB model. After
adding descriptive norm, subjective norm was no more significant. Other models
showed that conformity tendency was a strong predictor, indicating that the
presence of other pedestrians would influence behavioral intention. The findings
could help to design more effective interventions and safety campaigns, such as
changing people's attitude toward this violation behavior, correcting the social
norms, increasing their safety awareness, etc. in order to reduce pedestrians'
road crossing violations.
PMID- 26433569
TI - Reply from Authors re: Jean-Nicolas Cornu, Stephan Madersbacher. Greenlight
Photovaporisation of the Prostate: Now Ready for Prime Time. Eur Urol 2016;69:103
4.
PMID- 26433570
TI - A Systematic Review of Virtual Reality Simulators for Robot-assisted Surgery.
AB - CONTEXT: No single large published randomized controlled trial (RCT) has
confirmed the efficacy of virtual simulators in the acquisition of skills to the
standard required for safe clinical robotic surgery. This remains the main
obstacle for the adoption of these virtual simulators in surgical residency
curricula. OBJECTIVE: To evaluate the level of evidence in published studies on
the efficacy of training on virtual simulators for robotic surgery. EVIDENCE
ACQUISITION: In April 2015 a literature search was conducted on PubMed, Web of
Science, Scopus, Cochrane Library, the Clinical Trials Database (US) and the Meta
Register of Controlled Trials. All publications were scrutinized for relevance to
the review and for assessment of the levels of evidence provided using the
classification developed by the Oxford Centre for Evidence-Based Medicine.
EVIDENCE SYNTHESIS: The publications included in the review consisted of one RCT
and 28 cohort studies on validity, and seven RCTs and two cohort studies on
skills transfer from virtual simulators to robot-assisted surgery. Simulators
were rated good for realism (face validity) and for usefulness as a training tool
(content validity). However, the studies included used various simulation
training methodologies, limiting the assessment of construct validity. The review
confirms the absence of any consensus on which tasks and metrics are the most
effective for the da Vinci Skills Simulator and dV-Trainer, the most widely
investigated systems. Although there is consensus for the RoSS simulator, this is
based on only two studies on construct validity involving four exercises. One
study on initial evaluation of an augmented reality module for partial
nephrectomy using the dV-Trainer reported high correlation (r=0.8) between in
vivo porcine nephrectomy and a virtual renorrhaphy task according to the overall
Global Evaluation Assessment of Robotic Surgery (GEARS) score. In one RCT on
skills transfer, the experimental group outperformed the control group, with a
significant difference in overall GEARS score (p=0.012) during performance of
urethrovesical anastomosis on an inanimate model. Only one study included
assessment of a surgical procedure on real patients: subjects trained on a
virtual simulator outperformed the control group following traditional training.
However, besides the small numbers, this study was not randomized. CONCLUSIONS:
There is an urgent need for a large, well-designed, preferably multicenter RCT to
study the efficacy of virtual simulation for acquisition competence in and safe
execution of clinical robotic-assisted surgery. PATIENT SUMMARY: We reviewed the
literature on virtual simulators for robot-assisted surgery. Validity studies
used various simulation training methodologies. It is not clear which exercises
and metrics are the most effective in distinguishing different levels of
experience on the da Vinci robot. There is no reported evidence of skills
transfer from simulation to clinical surgery on real patients.
PMID- 26433571
TI - Metabolic Modulation of Clear-cell Renal Cell Carcinoma with Dichloroacetate, an
Inhibitor of Pyruvate Dehydrogenase Kinase.
AB - BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) exhibits suppressed
mitochondrial function and preferential use of glycolysis even in normoxia,
promoting proliferation and suppressing apoptosis. ccRCC resistance to therapy is
driven by constitutive hypoxia-inducible factor (HIF) expression due to genetic
loss of von Hippel-Lindau factor. In addition to promoting angiogenesis, HIF
suppresses mitochondrial function by inducing pyruvate dehydrogenase kinase
(PDK), a gatekeeping enzyme for mitochondrial glucose oxidation. OBJECTIVE: To
reverse mitochondrial suppression of ccRCC using the PDK inhibitor
dichloroacetate (DCA). DESIGN, SETTING, AND PARTICIPANTS: Radical nephrectomy
specimens from patients with ccRCC were assessed for PDK expression. The 786-O
ccRCC line and two animal models (chicken in ovo and murine xenografts) were used
for mechanistic studies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
Mitochondrial function, proliferation, apoptosis, HIF transcriptional activity,
angiogenesis, and tumor size were measured in vitro and in vivo. Independent
sample t-tests and analysis of variance were used for statistical analyses.
RESULTS: PDK was elevated in 786-O cells and in ccRCC compared to normal kidney
tissue from the same patient. DCA reactivated mitochondrial function (increased
respiration, Krebs cycle metabolites such as alpha-ketoglutarate [cofactor of
factor inhibiting HIF], and mitochondrial reactive oxygen species), increased p53
activity and apoptosis, and decreased proliferation in 786-O cells. DCA reduced
HIF transcriptional activity in an FIH-dependent manner, inhibiting angiogenesis
in vitro. DCA reduced tumor size and angiogenesis in vivo in both animal models.
CONCLUSIONS: DCA can reverse the mitochondrial suppression of ccRCC and decrease
HIF transcriptional activity, bypassing its constitutive expression. Its previous
clinical use in humans makes it an attractive candidate for translation to ccRCC
patients. PATIENT SUMMARY: We show that an energy-boosting drug decreases tumor
growth and tumor blood vessels in animals carrying human kidney cancer cells.
This generic drug has been used in patients for other conditions and thus could
be tested in kidney cancer that remains incurable.
PMID- 26433572
TI - Balanced Translocations Disrupting SMARCB1 Are Hallmark Recurrent Genetic
Alterations in Renal Medullary Carcinomas.
AB - BACKGROUND: Renal medullary carcinoma (RMC) is a rare and highly aggressive
neoplasm that most often occurs in the setting of sickle cell trait or sickle
cell disease (SCD). Most patients present with metastatic disease resistant to
conventional chemotherapy, and therefore there is an urgent need for molecular
insight to propose new therapies. OBJECTIVE: To determine the molecular
alterations and oncogenic pathways that drive RMC development. DESIGN, SETTING,
AND PARTICIPANTS: A series of five frozen samples of patients with RMC was
investigated by means of gene expression profiling, array comparative genomic
hybridization, and RNA and whole exome sequencing (WES). OUTCOME MEASUREMENTS AND
STATISTICAL ANALYSIS: RNA and DNA sequencing read data were analyzed to detect
gene fusions and somatic mutations. Gene fusions mutations were validated by real
time polymerase chain reaction and fluorescence in situ hybridization. Gene
expression profiling was analyzed by unsupervised hierarchical clustering and
Gene Set Enrichment Analysis (Broad Institute, Cambridge, MA, USA). RESULTS AND
LIMITATIONS: We observed inactivation of the tumor suppressor gene SMARCB1 in all
tumors. In all four cases developed in patients with SCD, we identified an
original mechanism of interchromosomal balanced translocations that disrupt the
SMARCB1 sequence and thus contribute to its inactivation. Gene expression
profiling revealed that RMC shares common oncogenic pathways with pediatric
malignant rhabdoid tumors, another tumor subtype characterized by SMARCB1
deficiency. CONCLUSIONS: RMCs are characterized by an original mechanism of
interchromosomal balanced translocations that disrupt the SMARCB1 sequence. WES
reveals that RMCs show no other recurrent genetic alteration and an overall
stable genome, underscoring the oncogenic potency of SMARCB1 inactivation.
PATIENT SUMMARY: Our comprehensive molecular study supports a pivotal role of the
tumor suppressor gene SMARCB1 in the development of renal medullary carcinoma.
The use of therapeutic strategies based on the biologic effects of its
inactivation should now open new perspectives for this typically lethal
malignancy.
PMID- 26433573
TI - Studying upper-limb kinematics using inertial sensors: a cross-sectional study.
AB - BACKGROUND: In recent years, there has been a great interest in analyzing upper
limb kinematics in order to investigate scapulohumeral rhythm, as its alteration
has been associated with shoulder joint complex injuries. The use of inertial
sensors is presented as a convenient and portable analysis method for studying
kinematics in terms of angular mobility and linear acceleration. The aim of this
study was to analyze upper-limbs kinematics in the three anatomical axes,
obtained by inertial sensors. RESULTS: Descriptive graphics of analytical tasks
performed were obtained. The main difference in mobility between the scapula and
humerus was found in pitch axis for abduction ([Formula: see text] = 107.6
degrees , SD = 9.3 degrees ) and flexion ([Formula: see text] = 113.1 degrees ,
SD = 9.3 degrees ). CONCLUSION: The use of inertial sensors for human kinematics
analysis is favorable. Although this study identified movement patterns, and
supports inertial sensors as a useful device to analyze upper-limb kinematics,
further studies with subjects with shoulder pathology to establish differences in
movement patterns and scapulohumeral rhythm between healthy and pathological
shoulders should be carried out.
PMID- 26433574
TI - The supply of general practitioners across local areas: accounting for spatial
heterogeneity.
AB - BACKGROUND: The geographic distribution of general practitioners (GPs) remains
persistently unequal in many countries despite notable increases in overall
supply. This paper explores how the factors associated with the supply of general
practitioners (GPs) are aligned with the arbitrary geographic boundaries imposed
by the use of spatially referenced GP supply data. METHODS: Data on GP supply in
postcodes within Australia are matched to data on the population characteristics
and levels of amenities in postcodes. Tobit regression models are used that
examine the associations between GP supply and postcode characteristics, whilst
accounting for spatial heterogeneity. RESULTS: The results demonstrate that GPs
do not consider space in a one-dimensional sense. Location choice is related to
both neighbourhood-specific factors, such as hospitals, and broader area factors,
such as area income and proximity to private schools. Although the proportion of
females and elderly were related to GPs supply, mortality rate was not.
CONCLUSIONS: This paper represents the first attempt to map the factors
influencing GP supply to the appropriate geographic level at which GPs may be
considering that factor. We suggest that both neighbourhood and broader regional
characteristics can influence GPs' locational choices. This finding is highly
relevant to the design and evaluation of relocation incentive programmes.
PMID- 26433575
TI - [Prevalence and determinants of anemia in young children in French-speaking
Africa. Role of iron deficiency].
AB - Anemia and iron deficiency are major public health issues worldwide and
particularly in Africa. Reliable information about their prevalence and
associated factors is required to allow for effective actions. In this study, we
used data from recent (2006-2012) large population health surveys, carried out in
11 French-speaking African countries (Benin, Burkina Faso, Cameroon, Congo
Brazzaville, Ivory Coast, Gabon, Guinea, Mali, Niger, Democratic Republic of
Congo, and Senegal). Hemoglobin (Hb) was assessed and demographic and health
related parameters were obtained from nation-representative samples of children
aged 6-59 months. Anemia (Hb<11g/dL) was found in 72.4% of the children (60.2
87.8%), with no gender difference but a slightly lower incidence in older
children (62% at age 4-5 years versus 85% at age 9 months), especially for the
more severe forms (2.1% versus 8.7%, respectively). Anemia was only slightly but
significantly affected by location (75.5% in rural areas versus 67.3% in towns),
income (79.8% in lower quintile of income versus 62.3% in higher quintile), or
maternal education (74.1% in children from non-educated mothers versus 62.4% in
children whose mothers had secondary education). Nearly 50% of women of child
bearing age had anemia. In the countries that report this information, less than
50% (17-65%) of children consumed iron-rich foods regularly and only 12% (7.4
20.5%) received iron supplementation. Infection and parasitism are known to
affect some markers of iron status, because of the inflammatory reaction, thereby
making the diagnosis of iron deficiency difficult. In the study countries, acute
respiratory diseases and diarrhea affected 6.2 and 15.6% of children aged between
6 and 59 months, respectively; their distribution according to age and location
is very different from the one of anemia, which is also the case for the
distribution of malaria. It is thus likely that a large part of the anemia
observed in young children is due to iron deficiency, although further research
is needed to confirm this. This fully justifies the nationwide programs of iron
fortification of flour, currently undergoing in most countries of French-speaking
Africa. Their formal evaluation is still pending but the initial data suggest
some efficacy, although far from optimal. It is thus likely that a more holistic
approach, including iron fortification, actions against undernutrition and
parasitism in children, and actions in favor of improving young women's iron and
nutritional status, together with appropriate communication and education
objectives, would be more effective.
PMID- 26433576
TI - [Morgagni-Larrey diaphragmatic hernia in a 3-month-old child affected by Marfan
syndrome].
AB - The authors report on a case of diaphragmatic hernia occurring in a 3-month-old
child affected by Marfan syndrome. Diagnosis was made on a chest X-ray and
cardiac ultrasounds, performed because of the association of poor general
condition, failure to thrive, and signs of respiratory distress. As a reminder,
we emphasize the association between Marfan disease and diaphragmatic hernias as
well as the diagnostic approach to reach an appropriate diagnosis.
PMID- 26433577
TI - [Hematologic abnormalities in infantile visceral leishmaniasis].
AB - The clinical and biological manifestations of visceral leishmaniasis are often
confusing, most particularly because it can mimic and lead to a variety of
hematological disorders. The aim of this study was to investigate the hematologic
abnormalities observed in infantile visceral leishmaniasis from January 2000 and
December 2013. The study included 35 children with a mean age of 3.5 years.
Clinical manifestations were dominated by splenomegaly, fever, and paleness,
defining the classic triad in 16% of our patients. Anemia was present in all
patients. Leukopenia was found in 51% of the cases. Thrombocytopenia was observed
in 48% of our patients and 36% had pancytopenia. All cases were confirmed by the
presence of Leishman bodies (amastigotes) in the bone marrow smears. Quantitative
and qualitative megakaryocyte abnormalities were found. Similarly,
dysgranulopoiesis was observed in 31% of the cases, eosinophilia was present in
6%, erythroid hypoplasia in 3%, and erythroid hyperplasia in 34%. Different
features of dyserythropoiesis were revealed in 71% of the patients with images of
hemophagocytosis in 6% and multiple dysplasias in 9%. The knowledge of these
hematological abnormalities associated with infantile visceral leishmaniasis can
assist us in searching for Leishman bodies in the bone marrow smears to provide a
diagnosis more quickly without necessarily resorting to more sophisticated tests.
PMID- 26433578
TI - Anti-inflammatory and Anti-oxidative Activities of Paeonol and Its Metabolites
Through Blocking MAPK/ERK/p38 Signaling Pathway.
AB - The possible protective and curative effects of paeonol on carrageenan-induced
acute hind paw edema in rats and dextran sulfate sodium (DSS)-induced colitis in
mice have been evaluated. After oral administration, paeonol (20 and 40 mg/kg)
reduced the edema increase in paw volumes and also the development of DSS-induced
murine colitis. Furthermore, anti-inflammatory and anti-oxidant activities of
paeonol (1) together with its 10 metabolites (M2~M11) were investigated by using
in vitro anti-inflammatory and anti-oxidant assays. M3 and M11 exhibited
significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities
(with EC50 values of 93.44 and 23.24 MUM, respectively). All the metabolites
except M8 showed hydroxyl radical scavenging activities, and M3 and M11 were the
most potent agents (with EC50 values of 336.02 and 124.05 MUM, respectively).
Inhibitory effects of paeonol, M2~M11 on the overproduction of nitric oxide (NO),
and the release of TNF-alpha were also tested. M3 and M11 potently inhibited
lipopolysaccharide (LPS)-induced overproduction of NO in macrophage RAW 264.7.
Western blot results demonstrated that paeonol, M3, and M11 downregulated the
high expression of inducible nitric oxide synthase (iNOS) and COX-2 proteins, and
the effects of M3 and M11 were more potent when compared with paeonol. These
findings indicated that paeonol may play anti-inflammatory and anti-oxidant roles
by changing to its active metabolites after absorption. In addition, further
investigations on the mechanism showed that paeonol, M3, and M11 blocked the
phosphorylation of MAPK/ERK 1/2 and p38, whereas they showed no effect on the
phosphorylation of JNK. The above results suggested that pre-treatment with
paeonol might be an effective therapeutic intervention against inflammatory
diseases including colitis.
PMID- 26433579
TI - Activation of Neutrophils via IP3 Pathway Following Exposure to Demodex
Associated Bacterial Proteins.
AB - Rosacea is a chronic inflammatory condition that predominantly affects the skin
of the face. Sera from rosacea patients display elevated reactivity to proteins
from a bacterium (Bacillus oleronius) originally isolated from a Demodex mite
from a rosacea patient suggesting a possible role for bacteria in the induction
and persistence of this condition. This work investigated the ability of B.
oleronius proteins to activate neutrophils and demonstrated activation via the
IP3 pathway. Activated neutrophils displayed increased levels of IP1 production,
F-actin formation, chemotaxis, and production of the pro-inflammatory cytokines
IL-1beta and IL-6 following stimulation by pure and crude B. oleronius protein
preparations (2 MUg/ml), respectively. In addition, neutrophils exposed to pure
and crude B. oleronius proteins (2 MUg/ml) demonstrated increased release of
internally stored calcium (Ca(2+)), a hallmark of the IP3 pathway of neutrophil
activation. Neutrophils play a significant role in the inflammation associated
with rosacea, and this work demonstrates how B. oleronius proteins can induce
neutrophil recruitment and activation.
PMID- 26433580
TI - Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired
renal function.
AB - PURPOSE: To evaluate the effect of renal impairment on eribulin mesylate
pharmacokinetics following a single dose in adults with advanced solid tumors.
METHODS: Patients were grouped by renal function: moderate impairment (creatinine
clearance [CrCl] 30-50 mL/min), severe impairment (CrCl 15-29 mL/min), or normal
(CrCl >=80 mL/min). During each 21-day cycle, eribulin mesylate doses (days 1 and
8) were administered intravenously: moderate, 1.1 mg/m(2) (except cycle 1 day 1,
1.4 mg/m(2)); severe, 0.7 mg/m(2); normal, 1.4 mg/m(2). RESULTS: Nineteen
patients were enrolled (normal, n = 6; moderate, n = 7; severe, n = 6). Renal
impairment was associated with an increased mean dose-normalized area under the
concentration-time curve (ratios for moderate/normal and severe/normal: 1.49; 90
% confidence interval [CI] 0.9, 2.45). CrCl and renal function correlated
positively, with a numerically small slope (0.0184; 90 % CI -0.00254, 0.0394). A
simulated dose reduction to eribulin 1.1 mg/m(2) in patients with moderate or
severe renal impairment achieved the same exposure as 1.4 mg/m(2) in those with
normal renal function. All groups had similar toxicity profiles, with no
unexpected adverse events. CONCLUSIONS: Renal impairment decreased eribulin
clearance and increased exposure. Pharmacokinetic evaluation supports an eribulin
dose reduction to 1.1 mg/m(2) in patients with moderate or severe renal
impairment. CLINICALTRIALS. GOV IDENTIFIER: NCT01418677.
PMID- 26433581
TI - A phase 1 study evaluating the pharmacokinetics and preliminary efficacy of
veliparib (ABT-888) in combination with carboplatin/paclitaxel in Japanese
subjects with non-small cell lung cancer (NSCLC).
AB - INTRODUCTION: Veliparib is a potent, orally bioavailable PARP inhibitor that
enhances efficacy of DNA-damaging chemotherapeutic agents. The study objectives
were to determine the recommended phase 2 dose (RPTD) of veliparib plus
carboplatin and paclitaxel, and assess pharmacokinetics (PK), tolerability, and
preliminary efficacy in Japanese patients with solid tumors. METHODS: Carboplatin
(AUC 6 mg/mL min) and paclitaxel (200 mg/m(2)) were administered on day 3 of a 21
day cycle. Oral veliparib (40, 80, or 120 mg BID) was administered on days 1-7.
Patients received <=6 cycles. Adverse events (AEs) were reported using NCI-CTCAE
version 4.03, PK parameters were analyzed using noncompartmental methods, and
responses were measured by RECIST version 1.1. RESULTS: Twelve patients with non
small cell lung cancer (NSCLC) were treated. Common treatment-emergent AEs,
consistent with toxicities associated with carboplatin and paclitaxel, included
leukopenia (100 %), neutropenia (100 %), anemia (83 %), thrombocytopenia (75 %),
increased alanine aminotransferase (67 %), and increased aspartate
aminotransferase (67 %). Grade 3/4 AEs (in >=2 patients) included neutropenia
(100 %), leukopenia (33 %), anemia (25 %), and hyponatremia (17 %). No AEs led to
veliparib, carboplatin, or paclitaxel interruption; no DLTs were observed. The
RPTD was determined to be 120 mg BID. Veliparib C max and AUC were approximately
dose proportional. Six partial responses were observed. CONCLUSIONS: Veliparib PK
was not impacted by carboplatin and paclitaxel. The safety profile was
manageable. The 120 mg BID RPTD confirmed in Japanese patients is the dose being
evaluated in global studies of veliparib. Preliminary efficacy suggests veliparib
may enhance carboplatin and paclitaxel activity, providing benefit to patients
with NSCLC.
PMID- 26433582
TI - The Arabidopsis thaliana NGATHA transcription factors negatively regulate cell
proliferation of lateral organs.
AB - The cell proliferation process of aerial lateral organs, such as leaves and
flowers, is coordinated by complex genetic networks that, in general, converge on
the cell cycle. The Arabidopsis thaliana NGATHA (AtNGA) family comprises four
members that belong to the B3-type transcription factor superfamily, and has been
suggested to be involved in growth and development of aerial lateral organs,
although its role in the cell proliferation and expansion processes remains to be
resolved in more detail. In order to clarify the role of AtNGAs in lateral organ
growth, we took a systematic approach using both the loss- and gain-of-functional
mutants of all four members. Our results showed that overexpressors of AtNGA1 to
AtNGA4 developed small, narrow lateral organs, whereas the nga1 nga2 nga3 nga4
quadruple mutant produced large, wide lateral organs. We found that cell numbers
of the lateral organs were significantly affected: a decrease in overexpressors
and, inversely, an increase in the quadruple mutant. Kinematic analyses on leaf
growth revealed that, compared with the wild type, the overexpressors displayed a
lower activity of cell proliferation and yet the mutant a higher activity.
Changes in expression of cell cycle-regulating genes were well in accordance with
the cell proliferation activities, establishing that the AtNGA transcription
factors act as bona fide negative regulators of the cell proliferation of aerial
lateral organs.
PMID- 26433583
TI - Delayed postoperative C5 root palsy and the use of neurophysiologic monitoring.
AB - INTRODUCTION: Although advances have been made in surgical technique and
intraoperative monitoring, the rate of postoperative C5 palsy remains the same.
We attempt to define characteristics which may predict risk of developing
postoperative C5 palsy. METHODS: Retrospective chart review identified 644
patients undergoing cervical procedures. Anterior cervical discectomy and fusion
was performed in 456, anterior cervical corpectomy and fusion (ACCF) in 78,
posterior laminectomy and fusion (PLF) in 106, and posterior open-door
laminoplasty in 4 patients. All patients had neurophysiologic monitoring
[somatosensory-evoked potentials (SSEP), spontaneous electromyogram (EMG), and/or
motor-evoked potential (MEP)]. RESULTS: Postoperative C5 root palsy occurred in 5
(2 with ACCF and 3 with PLF) cases (1.4%). In all cases, there were no changes in
intraoperative neurophysiologic monitoring. C5 palsy did not occur before
postoperative day 2. CONCLUSIONS: Patients undergoing cervical decompression
remain at risk for C5 root palsy despite use of monitoring. Given that all
patients experienced delayed onset of C5 palsy, MEP, SSEP, and EMG may not be
sensitive enough to assess the risk of developing C5 palsy.
PMID- 26433584
TI - Interest of T1 parameters for sagittal alignment evaluation of adolescent
idiopathic scoliosis patients.
AB - PURPOSE: In the last few years several reports stressed the importance of
sagittal alignment in adolescent idiopathic scoliosis (AIS) patients. It was
recently reported that T1 slope, defined as the angle between the superior
endplate of T1 and the horizontal, correlates strongly with overall sagittal
parameters. The aim of this study was to assess the impact of T1 parameters (T1
slope and T1-tilt) on sagittal alignment of AIS hypokyphotic patients
preoperatively and postoperatively. METHODS: Twenty-nine AIS patients with <20
degrees preoperative hypokyphosis were included in a retrospective study.
Surgery systematically comprised hybrid construct with screws below T11,
sublaminar bands at thoracic level and a lamino-laminar claw on the upper
instrumented vertebra. Preoperative, postoperative and 2-year follow-up
radiological assessment included Cobb angle, T1 slope, T1 sagittal tilt, regional
sagittal parameters and pelvic parameters. RESULTS: In the series as a whole,
coronal Cobb angle was significantly reduced postoperatively (58 degrees vs. 17
degrees ; p < 0.001), thoracic kyphosis significantly improved (12.4 degrees vs.
25.6 degrees ; p < 0.001) and cervical lordosis significantly restored (6.2
degrees kyphosis vs. 4.1 degrees lordosis; p < 0.001). There was a significant
modification in T1-slope (10.2 degrees vs. 18.2 degrees ; p < 0.001).
Preoperatively, T1 slope was significantly correlated with T1 tilt (r = 0.427; p
= 0.029). Postoperatively, T1 slope was significantly correlated with T1 tilt (r
= 0.549; p = 0.002), thoracic kyphosis (r = 0.535, p = 0.005) and cervical
lordosis (r = -0.444, p = 0.03). Restoration of cervical lordosis was
significantly correlated to changes of T1-slope (r = -0.393, p = 0.032), which
was significantly correlated to postoperative thoracic kyphosis. CONCLUSION:
According to these results, T1 seems to be of major interest in postoperative
modifications of sagittal alignment. T1 slope and sagittal tilt are good
indicators of postoperative changes for regional (cervical lordosis and thoracic
kyphosis) and global parameters. We therefore consider these parameters as
essential in the assessment of AIS patients. Further studies and correlation with
clinical scores will, however, be necessary in order to confirm the present
findings.
PMID- 26433585
TI - Relationship between modic changes and facet joint degeneration in the cervical
spine.
AB - PURPOSE: Given that the disc moves simultaneously with facet joints, there would
be a relationship between Modic changes and facet joint degeneration in the
cervical spine. However, there is no literature investigating the relationship.
The purpose is to evaluate the relationship between Modic changes and facet joint
degeneration in the cervical spine. METHODS: Ninety-eight patients underwent both
computed tomography (CT) and magnetic resonance images (MRI) of the cervical
spine. They consisted of fifty-one males and forty-eight females and their mean
age was 60.1 years (ranged from 40 years to 81 years). We compared the degree of
facet joint degeneration based on CTs with Modic changes based on MRIs from C2-C3
to C6-C7. The degree of facet joint degeneration was classified into four
categories and Modic changes were classified into four types. Disc degeneration
was determined with Miyazaki's grading system. RESULTS: Facet joint degeneration
was most common at C2-C3 and C4-C5 and rarest at C6-C7. Modic changes were most
common at C2-C3 and rarest at C6-C7. However, there was no relationship between
facet joint degeneration and any Modic changes at the same level. However, the
presence of facet joint degeneration and the presence of Modic change are common
in high grades of disc degeneration at the same level of the cervical spine.
CONCLUSION: Modic changes and facet joint degeneration are most common at C2-C3
in the cervical spine. However, there were no relationships between the presence
of Modic changes and facet joint degeneration at the same level of the cervical
spine.
PMID- 26433586
TI - A Computational Approach for the Prediction of Fatigue Behaviour in Peripheral
Stents: Application to a Clinical Case.
AB - Nickel-Titanium (NiTi) peripheral stents are commonly used for the treatment of
diseased femoropopliteal arteries (FPA). However, cyclic deformations of the
vessel, induced by limb movements affect device performance and fatigue failure
may occur. Stent strut fracture has been described in the literature, and is
implicated as a potential causative factor in vessel re-occlusion. In this paper,
a numerical approach is proposed to predict the fatigue behaviour of peripheral
NiTi stents within patient-specific arterial geometries, as additional
information to aid clinician intervention planning. The procedure needs some
patient-specific vessel features derived from routine clinical images but, when
this information is not available, reference data from the literature may be
used, obviously increasing the uncertainties of the results. In addition,
specific stent material data are required and can be obtained from experimental
tests. Several 3D finite element models resembling stented vessel segments are
built and used for fatigue analyses. For each model, axial cyclic boundary
conditions are obtained from a patient-specific lumped parameter model
representing the entire artery as a series of suitable springs. This allows the
simplification of stiffness changes along the vessel due to plaque and stent that
affect local axial deformations. Imposed local cyclic bending values depend on
the stent location along the FPA. The procedure is exemplified by its application
to an actual clinical case that showed two strut fractures at 18 months follow
up. Interestingly, despite the lack of some of patient-specific information and
the use of data from the literature to inform the model, the numerical approach
was able to interpret the in vivo fractures.
PMID- 26433587
TI - Transportable data from non-target arthropod field studies for the environmental
risk assessment of genetically modified maize expressing an insecticidal double
stranded RNA.
AB - As part of an environmental risk assessment, the potential impact of genetically
modified (GM) maize MON 87411 on non-target arthropods (NTAs) was evaluated in
the field. MON 87411 confers resistance to corn rootworm (CRW; Diabrotica spp.)
by expressing an insecticidal double-stranded RNA (dsRNA) transcript and the
Cry3Bb1 protein and tolerance to the herbicide glyphosate by producing the CP4
EPSPS protein. Field trials were conducted at 14 sites providing high geographic
and environmental diversity within maize production areas from three geographic
regions including the U.S., Argentina, and Brazil. MON 87411, the conventional
control, and four commercial conventional reference hybrids were evaluated for
NTA abundance and damage. Twenty arthropod taxa met minimum abundance criteria
for valid statistical analysis. Nine of these taxa occurred in at least two of
the three regions and in at least four sites across regions. These nine taxa
included: aphid, predatory earwig, lacewing, ladybird beetle, leafhopper, minute
pirate bug, parasitic wasp, sap beetle, and spider. In addition to wide regional
distribution, these taxa encompass the ecological functions of herbivores,
predators and parasitoids in maize agro-ecosystems. Thus, the nine arthropods may
serve as representative taxa of maize agro-ecosystems, and thereby support that
analysis of relevant data generated in one region can be transportable for the
risk assessment of the same or similar GM crop products in another region. Across
the 20 taxa analyzed, no statistically significant differences in abundance were
detected between MON 87411 and the conventional control for 123 of the 128
individual-site comparisons (96.1%). For the nine widely distributed taxa, no
statistically significant differences in abundance were detected between MON
87411 and the conventional control. Furthermore, no statistically significant
differences were detected between MON 87411 and the conventional control for 53
out of 56 individual-site comparisons (94.6 %) of NTA pest damage to the crop. In
each case where a significant difference was observed in arthropod abundance or
damage, the mean value for MON 87411 was within the reference range and/or the
difference was not consistently observed across collection methods and/or sites.
Thus, the differences were not representative of an adverse effect unfamiliar to
maize and/or were not indicative of a consistent plant response associated with
the GM traits. Results from this study support a conclusion of no adverse
environmental impact of MON 87411 on NTAs compared to conventional maize and
demonstrate the utility of relevant transportable data across regions for the ERA
of GM crops.
PMID- 26433588
TI - Why Narrating Changes Memory: A Contribution to an Integrative Model of Memory
and Narrative Processes.
AB - This paper aims to reflect on the relation between autobiographical memory (ME)
and autobiographical narrative (NA), examining studies on the effects of
narrating on the narrator and showing how studying these relations can make more
comprehensible both memory's and narrating's way of working. Studies that address
explicitly on ME and NA are scarce and touch this issue indirectly. Authors
consider different trends of studies of ME and NA: congruency vs incongruency
hypotheses on retrieving, the way of organizing memories according to gist or
verbatim format and their role in organizing positive and negative emotional
experiences, the social roots of ME and NA, the rules of conversation based on
narrating. Analysis of investigations leads the Authors to point out three basic
results of their research. Firstly, NA transforms ME because it narrativizes
memories according to a narrative format. This means that memories, when are
narrated, are transformed in stories (verbal language) and socialised. Secondly,
the narrativization process is determined by the act of telling something within
a communicative situation. Thus, relational situation of narrating act, by
modifying the story, modifies also memories. The Authors propose the RE.NA.ME
model (RElation, NArration, MEmory) to understand and study ME and NA. Finally,
this study claims that ME and NA refer to two different types of processes having
a wide area of overlapping. This is due to common social, developmental and
cultural roots that make NA to include part of ME (narrative of memory) and ME to
include part of NA (memory of personal events that have been narrated).
PMID- 26433589
TI - Cerebral Vasculitis in X-linked Lymphoproliferative Disease Cured by Matched
Unrelated Cord Blood Transplant.
AB - Vasculitis occurs rarely in association with X-linked lymphoproliferative disease
(XLP). There are four published cases of non-EBV XLP-associated cerebral
vasculitis reported, none of whom have survived without major cognitive
impairment. CASE: A 9-year old boy initially presented aged 5 years with a
restrictive joint disease. He subsequently developed dysgammaglobulinemia,
episodic severe pneumonitis, aplastic anaemia, gastritis and cerebral vasculitis.
A diagnosis of XLP was made, based on flow cytometric analysis and the
identification of a novel mutation in SH2D1A, c.96G>C. No peripheral blood
lymphocyte clonal proliferation was identified and he was EBV negative, although
human herpes virus-7 (HHV7) was detected repeatedly in his cerebrospinal fluid.
He underwent a reduced intensity unrelated umbilical cord blood transplant, but
failed to engraft. A second 5/6 matched cord gave 100 % donor engraftment.
Complications included BK virus-associated haemorrhagic cystitis, a possible NK
cell mediated immune reconstitution syndrome and post-transplant anti-glomerular
basement membrane disease, the latter treated with cyclophosphamide and
rituximab. At +450 days post-transplant he is in remission from his vasculitis
and anti-glomerular basement membrane disease, and HHV-7 has remained
undetectable. CONCLUSION: This is the second published description of joint
disease in XLP, and only the fourth case of non-EBV associated cerebral
vasculitis in XLP, as well as being the first to be successfully treated for this
manifestation. This case raises specific questions about vasculitis in XLP, in
particular the potential relevance of HHV-7 to the pathogenesis.
PMID- 26433590
TI - Sleeve Gastrectomy Reduces Body Weight and Improves Metabolic Profile also in
Obesity-Prone Rats.
AB - BACKGROUND: Susceptibility to obesity is associated with a notable inter
individual variation. The aim of the present study was to compare the
effectiveness of sleeve gastrectomy (SG) on weight loss and metabolic profile in
obesity-prone (OP) rats vs animals that are non-susceptible to obesity (NSO).
METHODS: Young male Wistar rats (n = 101) were put in a diet-induced obesity
(DIO) programme with ad libitum access to a high-fed diet (HFD) during 12 months.
Body weight and food intake were regularly registered. Thereafter, rats were
ranked by final body weight to identify the obesity-prone (OP) (n = 13) and non
susceptible to obesity (NSO) (n = 14) animals. OP and NSO rats were submitted to
surgical interventions (sham operation, SG and pair-fed to the amount of food
eaten by sleeve-gastrectomized rats). Body weight, food intake, energy
expenditure, body temperature, fat pads weight, and metabolic profiling were
analysed 4 weeks after surgical or dietary interventions. RESULTS: SG in both OP
and NSO rats decreased body weight as compared to sham and pair-fed groups (P <
0.05), mainly due to reductions in subcutaneous and perirenal fat mass (P <
0.001). Total weight loss achieved in sleeve-gastrectomized OP and NSO rats was
higher than that of pair-fed ones (P < 0.05), showing that the SG effect goes
beyond caloric restriction. In this regard, sleeve-gastrectomized rats exhibited
significantly (P < 0.05) increased basal rectal temperature together with
upregulated brown adipose tissue Ucp-1 protein expression levels. A significant
(P < 0.05) improvement in insulin sensitivity was also observed in both OP and
NSO animals that underwent SG as compared with pair-fed counterparts. CONCLUSION:
Our findings provide the first evidence that obesity-prone rats also benefit from
surgery responding effectively to SG, as evidenced by the significant body weight
reduction and the metabolic profile improvement.
PMID- 26433591
TI - Predictors of Excess Weight Loss in Obese Patients After Gastric Bypass: a 60
Month Follow-up.
AB - BACKGROUND: The objective of this study was to analyze the factors associated
with change in body mass index (BMI) and with percentage of excess weight loss
(%EWL) in patients undergoing Roux-en-Y gastric bypass (RYGB). The following
factors were analyzed: sex, age, surgical access (laparotomy vs. laparoscopy),
preoperative BMI, waist circumference (WC), type 2 diabetes mellitus (T2DM), high
blood pressure, and dyslipidemia. METHODS: Retrospective cohort study using a
convenience sample of 2070 patients of both sexes, aged 18 to 65 years,
undergoing RYGB between 2000 and 2013. The outcomes of interest were BMI and %EWL
at 0, 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months after RYGB. RESULTS: After
36, 48, and 60 months, approximately 50 % of patients had BMI >30 kg/m(2). As for
%EWL, 60-month results were poor for 17 % of patients (%EWL <50 %), good for 40 %
of patients (%EWL 50-75 %), very good for 24 % of patients (%EWL from >75-90 %),
and excellent for 19 % of patients (%EWL >90 %). The four most significant
predictors of BMI change 60 months after RYGB (in descending order of magnitude)
were preoperative BMI, preoperative WC, surgical access, and age; and of %EWL,
surgical access, preoperative BMI, preoperative WC, and age. CONCLUSIONS: After
60 months of follow-up, the most relevant predictors of weight loss after RYGB
were lower preoperative BMI and WC, videolaparoscopy as surgical access, and
younger age. Further studies must be carried out to elucidate the impact of these
factors on RYGB outcomes.
PMID- 26433592
TI - Imaging approaches to assess the therapeutic response of gastroenteropancreatic
neuroendocrine tumors (GEP-NETs): current perspectives and future trends of an
exciting field in development.
AB - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a family of neoplasms
with a complex spectrum of clinical behavior. Although generally more indolent
than carcinomas, once they progress beyond surgical resectability, they are
essentially incurable. Systemic treatment options have substantially expanded in
recent years for the management of advanced disease. Imaging plays a major role
in new drug development, as it is the main tool used to objectively evaluate
response to novel agents. However, current standard response criteria have proven
suboptimal for the assessment of the antiproliferative effect of many targeted
agents, particularly in the context of slow-growing tumors such as well
differentiated NETs. The aims of this article are to discuss the advantages and
limitations of conventional radiological techniques and standard response
assessment criteria and to review novel imaging modalities in development as well
as alternative cancer- and therapy-specific criteria to assess drug efficacy in
the field of GEP-NETs.
PMID- 26433593
TI - Systematic review of factors influencing extracellular vesicle yield from cell
cultures.
AB - The potential therapeutic utility of extracellular vesicles (EVs) has spawned an
interest into a scalable production, where the quantity and purity of EV samples
is sufficient for clinical applications. EVs can be isolated using several
different protocols; however, these isolation protocols and the subsequent
methods of quantifying the resulting EV yield have not been sufficiently
standardized. Therefore, the possibility of comparing different studies with
respect to these parameters is limited. In this review, we have presented factors
that might influence the yield and function of EVs from cell culture
supernatants. The methods of isolation, downstream quantification, and culture
conditions of the EV producing cells have been discussed. In order to examine the
inter-study coherency of EV yields, 259 studies were initially screened, and 46
studies were included for extensive downstream analysis of EV yields where
information pertaining to the isolation protocols and quantification methods was
obtained from each study. Several other factors influencing yield were compared,
such as cell type producing EVs, cell confluence level, and cell stimulation. In
conclusion, various factors may impact the resulting EV yield, including
technical aspects such as EV isolation and quantification procedures, and
biological aspects such as cell type and culture conditions. The reflections
presented in this review might aid in future standardization of the workflow in
EV research.
PMID- 26433594
TI - A Cost-effectiveness Analysis of Surgery, Endothermal Ablation, Ultrasound-guided
Foam Sclerotherapy and Compression Stockings for Symptomatic Varicose Veins.
AB - OBJECTIVE: The aim was to investigate the cost-effectiveness of interventional
treatment for varicose veins (VV) in the UK NHS, and to inform the national
clinical guideline on VV, published by the National Institute of Health and Care
Excellence. DESIGN: An economic analysis was constructed to compare the cost
effectiveness of surgery, endothermal ablation (ETA), ultrasound-guided foam
sclerotherapy (UGFS), and compression stockings (CS). The analysis was based on a
Markov decision model, which was developed in consultation with members of the
NICE guideline development group (GDG). METHODS: The model had a 5-year time
horizon, and took the perspective of the UK National Health Service. Clinical
inputs were based on a network meta-analysis (NMA), informed by a systematic
review of the clinical literature. Outcomes were expressed as costs and quality
adjusted life years (QALYs). RESULTS: All interventional treatments were found to
be cost-effective compared with CS at a cost-effectiveness threshold of L20,000
per QALY gained. ETA was found to be the most cost-effective strategy overall,
with an incremental cost-effectiveness ratio of L3,161 per QALY gained compared
with UGFS. Surgery and CS were dominated by ETA. CONCLUSIONS: Interventional
treatment for VV is cost-effective in the UK NHS. Specifically, based on current
data, ETA is the most cost-effective treatment in people for whom it is suitable.
The results of this research were used to inform recommendations within the NICE
guideline on VV.
PMID- 26433595
TI - Commentary on "Male Sex Associated With Increased Long-term Cardiovascular
Mortality After Peripheral Vascular Surgery for Atherosclerosis Despite Optimal
Medical Treatment".
PMID- 26433596
TI - Plasma and Synovial Fluid CXCL12 Levels Are Correlated With Disease Severity in
Patients With Knee Osteoarthritis.
AB - BACKGROUND: The aim is to determine whether CXC chemokine ligand-12 (CXCL12)
levels in plasma and synovial fluid (SF) of patients with knee osteoarthritis
(OA) are correlated with the disease severity. In addition, we set out to
investigate whether a peripheral blood test can avoid aspirating patients to
determine CXCL12 levels. METHODS: This study consisted of 244 patients with knee
OA and 244 age- and gender-matched healthy controls. Osteoarthritis progression
was classified based on Kellgren-Lawrence (KL) by evaluating radiographic changes
observed in anteroposterior knee radiography. The CXCL12 levels in the plasma and
SF were measured by a quantitative sandwich enzyme-linked immunosorbent assay.
RESULTS: Plasma CXCL12 levels were higher in OA patients as compared with
controls (P < .0001). There was a positive correlation between levels of CXCL12
and grade (P < .0001). Base on the receiver operating characteristic curve, the
optimal cutoff value of plasma CXCL12 levels as an indicator for screening of OA
was estimated to be 5.5 ng/mL, which yielded a sensitivity of 78.4% and a
specificity of 80.2%, with the area under the curve at 0.850 (95% confidence
interval [CI], 0.816-0.889; P < .0001). In multivariate analysis, there was an
increased risk of active OA associated with plasma CXCL12 levels >=10.5 ng/mL
(odds ratio, 6.76; 95% CI, 3.88-12.53; P < .0001) after adjusting for possible
confounders. Similarly, there was an increased risk of active OA associated with
SF CXCL12 levels >=15.0 ng/mL (odds ratio, 8.45; 95% CI, 3.23-18.22; P < .0001)
after adjusting for possible confounders. CONCLUSION: The CXCL12 levels in the
plasma and SF may serve as effective biomarkers for the severity of OA.
PMID- 26433597
TI - Load knowledge reduces rapid force production and muscle activation during
maximal-effort concentric lifts.
AB - PURPOSE: Rapid force development is a key factor influencing performance and
injury risk in movements where little time is available for force production;
thus there is a need to develop interventions that enhance this ability. In the
present study, the influence of load knowledge on mechanical output [rate of
force development; (RFD) and power] and muscle activation [electromyographic
(EMG) responses] in the concentric-only bench press throw exercise was studied.
METHODS: Fifteen strength-trained individuals performed 6 sets of 6 maximal
explosive repetitions in a single test session after extensive familiarization.
In three of these sets the subjects were given knowledge about the load before
each repetition (known condition; KC), whereas in the other three sets they were
given no information (unknown condition; UC). In both conditions the loads were
30, 50 and 70 % of maximum, but condition and load orders were randomized.
RESULTS: RFD (24-50 %) and power output (20-39 %) were significantly higher in UC
in the early time intervals from movement onset (<150 ms). In addition, UC
elicited greater EMG amplitudes in anterior deltoid both prior to movement onset
(pre50-0 ms) and in the early time intervals (<100 ms) after movement onset, and
in pectoralis major after movement onset (<100 ms). CONCLUSIONS: UC resulted in a
greater initial activation of the muscles and both a higher RFD and mechanical
power output in the early phase of the movement under all loading conditions (30
70 % of maximum). UC appears to offer a novel neuromuscular stimulus, and further
research on the effects of continued exposure is warranted.
PMID- 26433598
TI - Influence of acute passive stretching on the oxygen uptake vs work rate slope
during an incremental cycle test.
AB - PURPOSE: The aim of the study was to investigate the effects of acute passive
stretching on O2 uptake (VO2) vs work rate slope during a continuous incremental
ramp exercise. METHODS: On two different occasions, eight participants (age 23 +/
3 years; stature 1.71 +/- 0.10 m; body mass 68 +/- 8 kg; mean +/- SD) performed
two maximum incremental ramp tests on a cycle ergometer (25 W/min), with and
without pre-exercise stretching. During tests, we measured VO2 and other
metabolic and cardiorespiratory parameters on a breath-by-breath basis. The VO2
vs work rate slopes were calculated below (S 1) and above (S 2) the first
ventilatory threshold (VET1). RESULTS: With stretching: (1) peak VO2 did not
change, while peak work rate decreased (P < 0.05, ES = -0.41; CI -1.40/-0.58);
(2) in spite of a similar S 1, S 2 was steeper by about 11 % (P < 0.05; ES =
0.62; CI -0.38/-1.62). CONCLUSIONS: Stretching reduced peak work rate and altered
the [Formula: see text] vs work rate relationship above VET1 (S 2), without
affecting peak VO2. The present findings have practical implications, questioning
the use of stretching manoeuvres especially when peak work rate plays a key role
in exercise performance.
PMID- 26433600
TI - The Production of High Purity Phycocyanin by Spirulina platensis Using Light
Emitting Diodes Based Two-Stage Cultivation.
AB - Phycocyanin is a photosynthetic pigment found in photosynthetic cyanobacteria,
cryptophytes, and red algae. In general, production of phycocyanin depends mainly
on the light conditions during the cultivation period, and purification of
phycocyanin requires expensive and complex procedures. In this study, we propose
a new two-stage cultivation method to maximize the quantitative content and
purity of phycocyanin obtained from Spirulina platensis using red and blue light
emitting diodes (LEDs) under different light intensities. In the first stage,
Spirulina was cultured under a combination of red and blue LEDs to obtain the
fast growth rate until reaching an absorbance of 1.4-1.6 at 680 nm. Next, blue
LEDs were used to enhance the concentration and purity of the phycocyanin in
Spirulina. Two weeks of the two-stage cultivation of Spirulina yielded 1.28 mg
mL(-1) phycocyanin with the purity of 2.7 (OD620/OD280).
PMID- 26433599
TI - Characteristics of Recombinant Phytase (rSt-Phy) of the Thermophilic mold
Sporotrichum thermophile and its applicability in dephytinizing foods.
AB - Sporotrichum thermophile produces very low titres of phytase (St-Phy)
extracellularly, which is acidstable, thermostable, and protease insensitive with
broad substrate specificity, and therefore, the gene encoding phytase (St-Phy)
has been cloned and expressed in E. coli. The purified recombinant phytase (rSt
Phy) has the molecular mass of 55 kDa with Km and Vmax (calcium phytate), kcat
and kcat/Km of 0.143 mM, 185.05 nmoles mg(-1) s(-1), 5.1 * 10(3) s(-1), and 3.5
* 10(7) M(-1) s(-1), respectively. Mg(2+) and Ba(2+) display slight stimulatory
effect on the enzyme, while it is inhibited by other ions to a varied extent. The
enzyme is also inhibited by chaotropic agents (guanidinium hydrochloride,
potassium iodide, and urea), Woodward's reagent K, and 2,3-butanedione but
resistant to both pepsin and trypsin. The rSt-Phy is useful in dephytinization of
tandoori and naan (unleavened flat Indian breads), and bread, liberating soluble
inorganic phosphate that mitigates anti-nutrient effects of phytic acid.
PMID- 26433601
TI - Enhanced 3beta,7alpha,15alpha-Trihydroxy-5-Androsten-17-One Production from
Dehydroepiandrosterone by Colletotrichum lini ST-1 Resting Cells with Tween-80.
AB - 7alpha,15alpha-diOH-DHEA is a key precursor of the novel oral contraceptive
Yasmin. Colletotrichum lini could catalyze dehydroepiandrosterone (DHEA) at the
7alpha and 15alpha positions. In this work, C. lini resting cells were applied in
the bioconversion of DHEA to 7alpha,15alpha-diOH-DHEA. In the presence of 2 %
(w/v) Tween-80, the conversion efficiency of DHEA increased drastically. The DHEA
conversion and the 7alpha,15alpha-diOH-DHEA yield increased by 34.6 and 87.0 %,
respectively, at the DHEA concentration of 10 g/L. Furthermore, the effects of
Tween-80 on substrate solubility and C. lini physiological properties were
studied. Results showed that the DHEA solubility with 2 % Tween-80 increased by
7.8 times. Meanwhile, the mycelia were integrated and full in the presence of 2 %
Tween-80. The analysis on fatty acid profile of the C. lini cell membrane
indicated that Tween-80 increases the content of unsaturated fatty acid. All
above results suggested that the enhanced product yield caused by Tween-80 was
mainly associated with easier substrate-molecule transportation across the cell
membrane of C. lini.
PMID- 26433602
TI - Mixed Substrate Fermentation for Enhanced Phytase Production by Thermophilic
Mould Sporotrichum thermophile and Its Application in Beneficiation of Poultry
Feed.
AB - The optimum values of the critical variables determined by the central composite
design of response surface methodology (RSM) for maximum phytase production
(1881.26 U g(-1) dry mouldy residue (DMR)) by Sporotrichum thermophile are 2.5 %
Tween 80, 1.0 % yeast extract and 48 h of incubation period. Phytase production
in the mixed substrate (sugarcane bagasse and wheat bran) fermentation enhanced
11.6-fold over the initial production as a consequence of optimization. Phytase
titres are sustainable in flasks, trays and column bioreactor (1796 to 2095 U g(
1) DMR), thus validating the model and the process for large-scale phytase
production. When the yeast extract was replaced with corn steep liquor (2 % w/v),
a sustained enzyme titre (1890 U g(-1) DMR) was attained, making the process cost
effective. Among all the detergents, Tween 80 supported a higher phytase
production than others. The enzyme efficiently liberated nutritional components
from poultry feed (inorganic phosphate, soluble protein and reducing sugars) in a
time-dependent manner.
PMID- 26433603
TI - Evaluation of the fate and transport of chlorinated ethenes in a complex
groundwater system discharging to a stream in Wonju, Korea.
AB - Chlorinated ethenes such as trichloroethylene (TCE) are common and persistent
groundwater contaminants. If contaminated groundwater discharges to a stream,
then stream water pollution near the contamination site also becomes a problem.
In this respect, the fate and transport of chlorinated ethenes around a stream in
an industrial complex were evaluated using the concentration of each component,
and hydrogeochemical, microbial, and compound-specific carbon isotope data.
Temporal and spatial monitoring reveal that a TCE plume originating from main and
local source zones continues to be discharged to a stream. Groundwater
geochemical data indicate that aerobic conditions prevail in the upgradient area
of the studied aquifer, whereas conditions become anaerobic in the downgradient.
The TCE molar fraction is high at the main and local source zones, ranging from
87.4 to 99.2% of the total volatile organic compounds (VOCs). An increasing trend
in the molar fraction of cis-1, 2-Dichloroethene (cis-DCE) and vinyl chloride
(VC) was observed in the downgradient zone of the study area. The enriched
delta(13)C values of TCE and depleted values of cis-DCE in the stream zone,
compared to those of the source zone, also suggest biodegradation of VOCs.
Microbial community structures in monitoring wells adjacent to the stream zone in
the downgradient area were analyzed using 16S rRNA gene-based pyrosequencing to
identify the microorganisms responsible for biodegradation. This was attributed
to the high relative abundance of dechlorinating bacteria in monitoring wells
under anaerobic conditions farthest from the stream in the downgradient area. The
multilateral approaches adopted in this study, combining hydrogeochemical and
biomolecular methods with compound-specific analyses, indicate that contaminants
around the stream were naturally attenuated by active anaerobic biotransformation
processes.
PMID- 26433604
TI - Laterality as an indicator of emotional stress in ewes and lambs during a
separation test.
AB - We assessed motor laterality in sheep to explore species-specific brain hemi
field dominance and how this could be affected by genetic or developmental
factors. Further, we investigated whether directionality and strength of
laterality could be linked to emotional stress in ewes and their lambs during
partial separation. Forty-three ewes and their singleton lambs were scored on the
(left/right) direction of turn in a y-maze to rejoin a conspecific (laterality
test). Further, their behavioural response (i.e. time spent near the fence,
vocalisations, and activity level) during forced separation by an open-mesh fence
was assessed (separation test). Individual laterality was recorded for 44.2% ewes
(significant right bias) and 81.4% lambs (equally biased to the left and the
right). There was no significant association in side bias between dams and
offspring. The Chi-squared test revealed a significant population bias for both
groups (p < 0.05). Evolutionary adaptive strategies or stimuli-related visual
laterality may provide explanation for this decision-making process. Absolute
strength of laterality (irrespective of side) was high (Kolmogorov-Smirnov test,
dams: D = 0.2; p < 0.001; lambs: D = 0.36, p < 0.0001). The Wilcoxon test showed
that lateralised lambs and dams spent significantly more time near each other
during separation than non-lateralised animals (p < 0.05), and that lateralised
dams were also more active than non-lateralised ones. Arguably, the lateralised
animals showed a greater attraction to their pair because they were more
disturbed and thus required greater reassurance. The data show that measures of
laterality offer a potential novel non-invasive indicator of separation stress.
PMID- 26433605
TI - The effects of intervention on quality of telephone triage at an emergency unit
in Finland: Nurses' perspective.
AB - AIMS AND OBJECTIVES: The aim of this study was to investigate the effects of a
nurse training intervention on the assessment of patients' care needs in
telephone triage at an emergency unit. The objective of this study was to
generate information about nurse training that can be utilized when developing
telephone triage and health care education. BACKGROUND: With the growing number
of patients coming into emergency departments and a lack of resources in
healthcare, it would be valuable to determine an effective training intervention
in telephone triage, particularly when assessing the training needs of nurses.
DESIGN: The study was quasi-experimental, with a pre- and post-test design.
METHODS: The data were collected from the nurses at the emergency department and
joint emergency service of the Central Hospital in Northern Finland (baseline n =
28, post-test n = 26). The descriptive statistic, Fisher's chi(2) test and
McNemar's test were used to analyse the data. RESULTS: The intervention improved
nurses' skills to evaluate patients' needs and health condition via the telephone
triage. There was a statistically significant difference in the resources,
knowledge, skills and attitudes of the nurses between the baseline and post-test
measurements. CONCLUSIONS: The nurse training intervention improved the quality
of telephone triage. RELEVANCE TO CLINICAL PRACTICE: Nurses should receive
continuous training in telephone triage in order to maintain and reinforce their
professional competence. When planning the training, the age and relevant work
experience of the nurses should be taken into consideration as well, since the
results indicate that they lead to variation in the nurses' competence.
PMID- 26433606
TI - Age-dependent variation in innate immune responses to porcine epidemic diarrhea
virus infection in suckling versus weaned pigs.
AB - Porcine epidemic diarrhea (PED) is an enteric coronaviral infection that causes
severe morbidity and mortality in suckling pigs, but less severe disease in older
pigs. Consequently, it causes significant economic losses to the pork industry.
There are limited studies on the innate immune responses to PED virus (PEDV) in
pigs. The aims of our study were to investigate differences in innate immune
responses to PEDV infection in suckling and weaned pigs and to examine if disease
severity coincides with reduced innate immune responses. Weaned 26-day-old pigs
(n=20) and 9-day-old nursing pigs (n=20) were assigned to PEDV inoculated or
uninoculated control groups. The pigs were observed daily for clinical signs,
virus shedding and were euthanized at post-inoculation days (PIDs) 1 and 5 to
assay immune responses. Blood samples were collected at PIDs 1, 3 and 5. The
natural killer (NK) cell frequencies, NK cell activities (lysis of target K562
tumor cells in vitro), CD3+CD4+ T cell and CD3+CD8+ T cell frequencies were
measured in blood and ileum at PIDs 1 and 5. The PEDV infected suckling pigs
showed severe diarrhea and vomiting at PID 1, whereas the PEDV infected weaned
pigs showed milder clinical signs starting at PID 3. PEDV infected suckling pigs
had significantly higher diarrhea scores, earlier fecal PEDV RNA shedding and
significantly higher viremia (viral RNA in serum) compared to weaned pigs. There
was no mortality in either infected suckling or infected weaned pigs. The control
pigs not inoculated with PEDV did not show any clinical signs and no detectable
fecal or serum PEDV RNA. Strikingly, PEDV infected suckling pigs had
significantly lower NK cell frequencies, undetectable NK cell activity and lower
IFNgamma producing NK cells in blood and ileum compared to PEDV infected weaned
pigs. Pro-inflammatory cytokine profiles of PEDV infected suckling pigs differed
from those of PEDV infected weaned pigs and coincided with onset of fecal PEDV
RNA shedding and serum PEDV RNA titers. The infected suckling pigs have higher
and earlier increases in serum IFNalpha, but lower serum IL-8 and TNFalpha levels
compared to infected weaned pigs. CD3+CD4+ T cell frequencies were significantly
higher in ileum of suckling pigs than in weaned pigs, whereas there was no
difference in CD3+CD8+ T cell frequencies. In conclusion, the observations of
impaired lytic activity and IFN-gamma production by NK cells in suckling pigs
coincided with the increased severity of PEDV infection in the suckling pigs
compared with the weaned pigs.
PMID- 26433607
TI - Not an Aspirin: No Evidence for Acute Anti-Nociception to Laser-Evoked Pain After
Motor Cortex rTMS in Healthy Humans.
AB - BACKGROUND: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS)
has shown efficacy in relieving neuropathic pain. Whether its analgesic effect
also applies to acute physiological nociception remains unclear due to previous
contradictory findings. OBJECTIVE: To provide an in-depth investigation of the
effects of motor cortex HF-rTMS on acute laser-evoked pain and excitability of
nociceptive networks in healthy subjects. METHODS: Randomized, placebo
controlled, double-blind, cross-over study in 20 healthy participants. Laser heat
stimuli at nociceptive threshold were delivered to the right hand, allowing
assessment of: (a) subjective pain intensity and unpleasantness; (b) laser-evoked
potentials (LEPs, 128 electrodes) and their source model; (c) sympathetic skin
responses, and (d) spino-thalamic pathway excitability. Data were collected
before and 20 minutes after a session of neuro-navigated 20 Hz rTMS to the
contralateral motor cortex. RESULTS: Subjective pain reports to thermal laser
pulses, amplitude of late cortical potentials and sympathetic skin responses were
decreased after cortical stimulation, to a similar extent whether it was active
or placebo. Early cortical potentials and nociceptive network excitability
remained identical before and after rTMS, as did anatomical sources of LEPs.
CONCLUSIONS: Our results do not provide evidence for a genuine anti-nociceptive
effect of rTMS on acute physiological pain. We suggest that motor cortex rTMS may
act upon high-order networks linked to the emotional and cognitive appraisal of
chronic pain, and/or modulate pathologically sensitized networks, rather than
change the physiological transmission within an intact nervous system. Such
dichotomy is reminiscent of that observed with most drugs used for neuropathic
pain.
PMID- 26433608
TI - Trigeminal Nerve Stimulation (TNS) for the Treatment of Irritable Bowel Syndrome
in an Elderly Patient with Major Depressive Disorder: A Case Study.
PMID- 26433609
TI - Transcranial Direct Current Stimulation Post-Stroke Upper Extremity Motor
Recovery Studies Exhibit a Dose-Response Relationship.
AB - BACKGROUND AND PURPOSE: Transcranial direct current stimulation (tDCS) has shown
mixed results in post-stroke motor recovery, possibly because of tDCS dose
differences. The purpose of this meta-analysis was to explore whether the outcome
has a dose-response relationship with various dose-related parameters. METHODS:
The literature was searched for double-blind, randomized, sham-controlled
clinical trials investigating the role of tDCS (>=5 sessions) in post-stroke
motor recovery as measured by the Fugl-Meyer Upper Extremity (FM-UE) scale.
Improvements in FM-UE scores were compared between active and sham groups by
calculating standardized mean differences (Hedge's g) to derive a summary effect
size. Inverse-variance-weighted linear meta-regression across individual studies
was performed between various tDCS parameters and Hedge's g to test for dose
response relationships. RESULTS: Eight studies with total of 213 stroke subjects
were included. Summary Hedge's g was statistically significant in favor of the
active group (Hedge's g = 0.61, p = 0.02) suggesting moderate effect.
Specifically, studies that used bihemispheric tDCS montage (Hedge's g = 1.30, p =
0.08) or that recruited chronic stroke patients (Hedge's g = 1.23, p = 0.02)
showed large improvements in the active group. A positive dose-response
relationship was found with current density (p = 0.017) and charge density (p =
0.004), but not with current amplitude. Moreover, a negative dose-response
relationship was found with electrode size (p < 0.001, smaller electrodes were
more effective). CONCLUSIONS: Our meta-analysis and meta-regression results
suggest superior motor recovery in the active group when compared to the sham
group and dose-response relationships relating to electrode size, charge density
and current density. These results need to be confirmed in future dedicated
studies.
PMID- 26433610
TI - Alcohol Intoxication by Binge Drinking Impairs Neuroplasticity.
AB - BACKGROUND: Binge drinking, resulting in acute alcohol intoxication, is
considered an initial step in developing alcohol use disorders (AUDs). It has
been suggested that alcohol intoxication may act on mechanisms of neuroplasticity
to produce brain changes that contribute to the pathophysiology of AUDs. However,
the effect of binge drinking on neuroplasticity has not been evaluated in humans.
OBJECTIVE: The current study was aimed at evaluating the effect of a binge
drinking episode on LTP-like neuroplasticity. METHODS: In a within-subject
randomized, cross-over design, fifteen otherwise healthy binge drinkers were
administered paired associative stimulation (PAS) following consumption of
alcohol or a placebo beverage. PAS is an experimental paradigm that allows for
the induction of associative long-term potentiation (LTP)-like neuroplasticity.
Subjects were administered alcohol at a dose of 1.5 g/l of body water, producing
a peak blood alcohol concentration (BAC) of 26.1 mM (0.120% BAC). PAS induced
neuroplasticity was measured at Post 0 (immediately following PAS), Post 15 (15
minutes following PAS), Post 30 (30 minutes following PAS), Post 60 (60 minutes
following PAS) and Post Day 1 (the next day following PAS). RESULTS: The binge
drinking episode inhibited LTP-like neuroplasticity, which was significantly
different from placebo at 30 and 60 min following the PAS administration.
Examination of longitudinal effects revealed no differences between beverages on
LTP-like neuroplasticity the following day. CONCLUSIONS: Findings suggest that
binge drinking impairs neuroplasticity and while these effects are no longer
evident the day after a single binge session, repetitive binging may produce long
lasting changes in neuroplasticity that contribute to the development of AUDs.
PMID- 26433611
TI - Implementation of a multidisciplinary clinical pathway for the management of
postpartum hemorrhage: a retrospective study.
AB - OBJECTIVE: To compare the outcomes of postpartum hemorrhage (PPH) episodes before
and after the introduction of a clinical pathway known as the Severance Protocol
to save postpartum bleeding through Expeditious care Delivery (SPEED). DESIGN:
This study was designed as a retrospective analysis. SETTING: The study was
conducted in a hospital implementing SPEED. PARTICIPANTS: The non-SPEED group
included 74 patients with PPH who were treated before the introduction of SPEED,
whereas the SPEED group included 155 patients. METHODS: Differences in outcomes
were compared between groups. MAIN OUTCOME MEASURES: Reduction in treatment
duration was the primary outcome measure, whereas uterus preservation was the
secondary. RESULTS: No significant intergroup differences were observed for
hemoglobin levels, hematocrit values and vital signs upon patients' emergency
room arrival. The turnaround time for hemoglobin, mean duration until treatment
by obstetricians and gynecologists and duration between chest radiography
ordering and performance significantly differed between the two groups (SPEED,
10.0 [1.0-30.0], 3.0 [0-25.0] and 23.0 [1.0-86.0] min, respectively; non-SPEED,
17.0 [1.0-37.0], 12.0 [0-62.0] and 46.0 [1.0-580.0] min, respectively; P <
0.001). Similarly, the mean duration until transfusion of cross-matched red blood
cells (SPEED, 77.6 +/- 58.6 min; non-SPEED, 103.4 +/- 64.4 min; P = 0.015) and
uterus preservation rate (SPEED, 90.1% [136/151]; non-SPEED, 81.7% [58/71]; P =
0.043) also differed significantly between the groups. CONCLUSIONS: Clinical
pathways enable prompt and efficient care for patients experiencing PPH through
faster evaluation and access to red blood cell transfusion, resulting in a
decrease in maternal mortality.
PMID- 26433612
TI - Estimating DNA methylation levels by joint modeling of multiple methylation
profiles from microarray data.
AB - DNA methylation studies have been revolutionized by the recent development of
high throughput array-based platforms. Most of the existing methods analyze
microarray methylation data on a probe-by-probe basis, ignoring probe-specific
effects and correlations among methylation levels at neighboring genomic
locations. These methods can potentially miss functionally relevant findings
associated with genomic regions. In this article, we propose a statistical model
that allows us to pool information on the same probe across multiple samples to
estimate the probe affinity effect, and to borrow strength from the neighboring
probe sites to better estimate the methylation values. Using a simulation study,
we demonstrate that our method can provide accurate model-based estimates. We
further use the proposed method to develop a new procedure for detecting
differentially methylated regions, and compare it with a state-of-the-art
approach via a data application.
PMID- 26433613
TI - The R900S mutation in CACNA1S associated with hypokalemic periodic paralysis.
AB - Primary hypokalemic periodic paralysis is an autosomal dominant skeletal muscle
channelopathy. In the present study, we investigated the genotype and phenotype
of a Chinese hypokalemic periodic paralysis family. We used whole-exome next
generation sequencing to identify a mutation in the calcium channel, voltage
dependent, L type, alpha subunit gene (CACNA1S), R900S, which is a rare mutation
associated with hypokalemic periodic paralysis. We first present a clinical
description of hypokalemic periodic paralysis patients harboring CACNA1SR900S
mutations: they were non-responsive to acetazolamide, but combined treatment with
triamterene and potassium supplements decreased the frequency of muscle weakness
attacks. All male carriers of the R900S mutation experienced such attacks, but
all three female carriers were asymptomatic. This study provides further evidence
for the phenotypic variation and pharmacogenomics of hypokalemic periodic
paralysis.
PMID- 26433615
TI - A bifurcation identifier for IV-OCT using orthogonal least squares and supervised
machine learning.
AB - Intravascular optical coherence tomography (IV-OCT) is an in-vivo imaging
modality based on the intravascular introduction of a catheter which provides a
view of the inner wall of blood vessels with a spatial resolution of 10-20 MUm.
Recent studies in IV-OCT have demonstrated the importance of the bifurcation
regions. Therefore, the development of an automated tool to classify hundreds of
coronary OCT frames as bifurcation or nonbifurcation can be an important step to
improve automated methods for atherosclerotic plaques quantification, stent
analysis and co-registration between different modalities. This paper describes a
fully automated method to identify IV-OCT frames in bifurcation regions. The
method is divided into lumen detection; feature extraction; and classification,
providing a lumen area quantification, geometrical features of the cross
sectional lumen and labeled slices. This classification method is a combination
of supervised machine learning algorithms and feature selection using orthogonal
least squares methods. Training and tests were performed in sets with a maximum
of 1460 human coronary OCT frames. The lumen segmentation achieved a mean
difference of lumen area of 0.11 mm(2) compared with manual segmentation, and the
AdaBoost classifier presented the best result reaching a F-measure score of 97.5%
using 104 features.
PMID- 26433614
TI - Robust anatomical landmark detection with application to MR brain image
registration.
AB - Comparison of human brain MR images is often challenged by large inter-subject
structural variability. To determine correspondences between MR brain images,
most existing methods typically perform a local neighborhood search, based on
certain morphological features. They are limited in two aspects: (1) pre-defined
morphological features often have limited power in characterizing brain
structures, thus leading to inaccurate correspondence detection, and (2)
correspondence matching is often restricted within local small neighborhoods and
fails to cater to images with large anatomical difference. To address these
limitations, we propose a novel method to detect distinctive landmarks for
effective correspondence matching. Specifically, we first annotate a group of
landmarks in a large set of training MR brain images. Then, we use regression
forest to simultaneously learn (1) the optimal sets of features to best
characterize each landmark and (2) the non-linear mappings from the local patch
appearances of image points to their 3D displacements towards each landmark. The
learned regression forests are used as landmark detectors to predict the
locations of these landmarks in new images. Because each detector is learned
based on features that best distinguish the landmark from other points and also
landmark detection is performed in the entire image domain, our method can
address the limitations in conventional methods. The deformation field estimated
based on the alignment of these detected landmarks can then be used as
initialization for image registration. Experimental results show that our method
is capable of providing good initialization even for the images with large
deformation difference, thus improving registration accuracy.
PMID- 26433616
TI - Synthesis and pharmacological evaluation of some new fluorine containing
hydroxypyrazolines as potential anticancer and antioxidant agents.
AB - Breast cancer is probably the most prevalent cancer in women. The development of
resistance to therapeutic agents and lack of targeted therapy for breast cancer
cells provide motivation to identify new compounds for the treatment. With this
objective in mind, a new series of 3-fluoro-4-methoxyphenyl group based 1,3,5
trisubstituted aryl-5-hydroxypyrazoline analogues 4a-l was synthesized through
multi-step reaction sequence. The structures of the newly synthesized compounds
were confirmed by IR, (1)H NMR, (13)C NMR, LC-MS and elemental analysis. They
were screened for their in vitro anticancer and in vitro antioxidant activities.
Among the tested compounds 4h, 4c and particularly 4i displayed promising
cytotoxic effect on breast cancer cell lines. The compounds were also found to
possess antioxidant activity when tested against DPPH free radical. Overall, this
work has contributed to the development of promising leads for anticancer and
antioxidant activities.
PMID- 26433617
TI - alpha-Halogenated oxaphosphinanes: Synthesis, unexpected reactions and evaluation
as inhibitors of cancer cell proliferation.
AB - This paper describes the preparation and the biological evaluation of alpha
halogenated oxaphosphinanes. These halogen derivatives were synthetized from a
short and stereoselective synthetic sequence starting by previously described
hydroxy-precursors 1 and 2 with respectively a glucose and mannose-like
configuration. The in vitro biological tests of these unnatural halogenated
phosphinosugars, on several cell lines, highlighted, for some of them, their
antiproliferative and anti migration and invasion properties at nanomolar
concentration.
PMID- 26433618
TI - Antiproliferative, DNA intercalation and redox cycling activities of
dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure-activity
relationship study.
AB - The anticancer agent YM155 is widely investigated as a specific survivin
suppressant. More recently, YM155 was found to induce DNA damage and this has
raised doubts as to whether survivin is its primary target. In an effort to
assess the contribution of DNA damage to the anticancer activity of YM155,
several analogs were prepared and evaluated for antiproliferative activity on
malignant cells, participation in DNA intercalation and free radical generation
by redox cycling. The intact positively charged scaffold was found to be
essential for antiproliferative activity and intercalation but was less critical
for redox cycling where the minimal requirement was a pared down bicyclic
quinone. Side chain requirements at the N(1) and N(3) positions of the scaffold
were more alike for redox cycling and intercalation than antiproliferative
activity, underscoring yet again, the limited structural overlaps for these
activities. Furthermore, antiproliferative activities were poorly correlated to
DNA intercalation and redox cycling. Potent antiproliferative activity (IC50 9-23
nM), exceeding that of YM155, was found for a minimally substituted methyl analog
AB7. Like YM155 and other dioxonaphthoimidazoliums, AB7 was a modest DNA
intercalator but with weak redox cycling activity. Thus, the capacity of this
scaffold to inflict direct DNA damage leading to cell death may not be
significant and YM155 should not be routinely classified as a DNA damaging agent.
PMID- 26433620
TI - Application of genome editing technologies to the study and treatment of
hematological disease.
AB - Genome editing technologies have advanced significantly over the past few years,
providing a fast and effective tool to precisely manipulate the genome at
specific locations. The three commonly used genome editing technologies are Zinc
Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases
(TALENs), and the Clustered Regularly Interspaced Short Palindromic Repeats
(CRISPR)-associated Cas9 (CRISPR/Cas9) system. ZFNs and TALENs consist of
endonucleases fused to a DNA-binding domain, while the CRISPR/Cas9 system uses
guide RNAs to target the bacterial Cas9 endonuclease to the desired genomic
location. The double-strand breaks made by these endonucleases are repaired in
the cells either by non-homologous end joining, resulting in the introduction of
insertions/deletions, or, if a repair template is provided, by homology directed
repair. The ZFNs, TALENs and CRISPR/Cas9 systems take advantage of these repair
mechanisms for targeted genome modification and have been successfully used to
manipulate the genome in human cells. These genome editing tools can be used to
investigate gene function, to discover new therapeutic targets, and to develop
disease models. Moreover, these genome editing technologies have great potential
in gene therapy. Here, we review the latest advances in the application of genome
editing technology to the study and treatment of hematological disorders.
PMID- 26433619
TI - Faecal microbiota transplantation in recurrent Clostridium difficile infection:
Recommendations from the French Group of Faecal microbiota Transplantation.
AB - Faecal microbiota transplantation is effective for treating recurrent forms of
Clostridium difficile infection and its use in this indication is recommended in
the most recent European and North American guidelines. In this context, faecal
microbiota transplantation is beginning to be performed in France in clinical
practice, while the rules governing this procedure have been defined in France
only for clinical trials. To unify, secure, and evaluate practice in this field
in France, the French Group of Faecal microbiota Transplantation (FGFT) was
created in October 2014 with the support of the French National Society of
Gastroenterology, the French Infectious Disease Society, and the National Academy
of Pharmacy. We present here the deliberations of this group regarding the use of
faecal microbiota transplantation for recurrent Clostridium difficile infection.
The issues addressed are the indications, therapeutic sequence, delivery
procedures, donor selection, methods and conditions of specimen preparation, and
traceability.
PMID- 26433621
TI - Response to Commentary: 'Retrospective study of the association between epidural
analgesia during labour and complications for the newborn'. Authors: Herrera
Gomez A, MsC; Garcia-Martinez O, PhD; Ramos-Torrecillas J, PhD; De Luna-Bertos E,
PhD; Ruiz C, PhD; Ocana-Peinado FM, PhD.
PMID- 26433622
TI - Women's help-seeking behaviours for depressive symptoms during the perinatal
period: Socio-demographic and clinical correlates and perceived barriers to
seeking professional help.
AB - OBJECTIVE: This study aims to characterize the help-seeking behaviours of women
who were screened positive for perinatal depression, to investigate its
sociodemographic and clinical correlates, and to characterize the perceived
barriers that prevent women from seeking professional help. DESIGN: Cross
sectional internet survey. SETTING: Participants were recruited through
advertisements published in pamphlets and posted on social media websites (e.g.,
Facebook) and websites and forums that focused on pregnancy and childbirth.
PARTICIPANTS: 656 women (currently pregnant or who had a baby during the last 12
months) completed the survey. MEASUREMENTS: Participants were assessed with the
Edinburgh Postpartum Depression Scale, and were questioned about sociodemographic
and clinical data, help-seeking behaviours and perceived barriers to help
seeking. FINDINGS: Different pathways of help-seeking were found, with only 13.6%
of women with a perinatal depression seeking help for their emotional problems.
Married women, currently pregnant women, and women without history of
psychological problems had a higher likelihood of not engaging in any type of
help-seeking behaviour. The majority of women who had not sought professional
assistance identified several barriers to help-seeking, particularly knowledge
barriers. KEY CONCLUSIONS: Strategies to increase women's help-seeking behaviours
should be implemented, namely improving mental health literacy, introducing
screening procedures for mental health problems in pre/postnatal health care
settings, and offering women innovative opportunities (e.g., web-based tools)
that allow them to overcome the practical barriers to help-seeking.
PMID- 26433624
TI - Magnetic resonance imaging in the assessment of anomalous pulmonary venous
connections.
AB - OBJECTIVE: To illustrate the morphological and functional magnetic resonance
findings for total and partial anomalous pulmonary venous connections as well as
of the most common complications after surgery. CONCLUSION: The magnetic
resonance findings are fundamental in defining the type of anomalous connection,
deciding on the treatment, planning the surgery, and detecting postsurgical
complications.
PMID- 26433623
TI - [Imaging findings in cardiac masses. Part II: malignant tumors and pseudotumors].
AB - Malignant heart tumors are less common than benign ones. They can be primary or
secondary. Secondary or metastatic heart tumors are 20 to 40 times more common
than primary malignant heart tumors, which have an estimated incidence of 0.05%.
Non-neoplastic pseudotumors can present as cardiac masses, with imaging
characteristics than can suggest the diagnosis of a tumor. The aim of this
article is to describe and illustrate malignant heart tumors and pseudotumors,
stressing the CT and MRI findings that make it possible to differentiate them
from benign cardiac tumors.
PMID- 26433625
TI - Triple-negative breast carcinoma: heterogeneity in immunophenotypes and
pharmacokinetic behavior.
AB - OBJECTIVES: To evaluate the morphokinetic, pharmacokinetic, and diffusion
characteristics of triple-negative breast cancers on magnetic resonance (MR)
imaging and to analyze whether there is a relation between these parameters and
the time to progression. MATERIAL AND METHODS: This was a retrospective
observational study of a consecutive series of 100 patients with histologically
confirmed triple-negative breast cancer studied at our center between January
2005 and December 2010. We reviewed the findings on MR locoregional extension
studies, the histological findings, and the follow-up of patients until August
2014. RESULTS: The most common MR findings for these tumors were a rounded mass
(47.3%), well-defined borders (53.7%), ring enhancement (46.2%), type 3 curves
(50.5%), hyperintensity within the tumor on T2-weighted sequences, high ADC
values (1.04 * 10(-3) mm2/s), and increased capillary permeability (Kep) (0.94
min(-1)). No significant association was observed between the morphokinetic or
pharmacokinetic characteristics and the time to progression. The in situ
component in the surgical specimens was high, although its expression was low.
During follow-up, 25% of patients had metastases, with a predilection for the
visceral organs, and survival was low. CONCLUSION: Tumors with the triple
negative phenotype mostly presented in MR as rounded tumors with well-defined
borders and ring enhancement. We found no significant association between the
morphokinetic or pharmacokinetic characteristics and the time to progression.
PMID- 26433626
TI - Interim (18)F-Fluorodeoxyglucose Positron Emission Tomography for Early Metabolic
Assessment of Response to Cisplatin, Etoposide, and Bleomycin Chemotherapy for
Metastatic Seminoma: Clinical Value and Future Directions.
AB - BACKGROUND: In patients with metastatic seminoma, designing a risk-adapted
strategy that may help personalize the burden of treatment and follow-up is
required. PATIENTS AND METHODS: Patients who were administered cisplatin,
etoposide, and bleomycin (PEB) were staged at baseline with computed tomography
(CT), positron emission tomography (PET), and serum tumor markers. Restaging was
then performed with PET after 2 cycles of PEB (PET2) and with CT after 3 to 4
cycles of treatment. The 20% cutoff of maximal standardized uptake value (SUVmax)
changes and Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1)
criteria were applied to define the response. The Wilcoxon rank sum test was used
to analyze the association between metabolic response and the shrinkage of target
lesions. RESULTS: Between February 2009 and November 2013, 37 patients were
enrolled. After 2 cycles of PEB, 27 patients (72.9%; 95% confidence interval
[CI], 55.8-86.2) had a metabolic complete response (CR) and 10 patients had a
partial response (PR; 27%; 95% CI, 13.8-44.1). A significant association was
found between PET2 response and baseline (P = .003), final diameter (P < .001),
and percentage of tumor shrinkage (P = .014) of target lesions. After 18 months'
(interquartile range [IQR], 13-23) median follow-up, 2 patients with PET2 PR had
relapsed disease; none of those with a CR had relapsed disease. CONCLUSIONS: A
significant association was found between early metabolic response and tumor
shrinkage in patients with advanced seminoma. Patients achieving a PET2 CR could
be predicted not to need additional treatment after PEB, and simplifying their
follow-up should be an end point. PET2 might also identify difficult to treat
cases at an early stage.
PMID- 26433628
TI - Vaccine monitoring systems: A potential model for medications in pregnancy.
AB - Multiple vaccine safety systems contribute to monitor and assess the safety of
vaccines given to pregnant women and their offspring. This article presents a
review of the strengths and limitations of several national vaccine safety
systems. The review concludes that the present framework of vaccine safety
systems offers lessons to be learned toward the design of a system for monitoring
and assessing the safety of medications administered to pregnant women in
clinical practice and research.
PMID- 26433627
TI - Effective and Safe Administration of Low-Dose Estramustine Phosphate for
Castration-Resistant Prostate Cancer.
AB - Despite the favorable toxicity profile at the standard dose of 560 mg daily, the
tolerability and toxicology of estramustine phosphate (EMP) have been a cause for
concern at administration. Moreover, we do not know whether a lower dose of 280
mg of EMP daily can be administered with some efficacy and fewer side effects.
The results of our phase II study suggest that low-dose EMP is a safe treatment
option with the same efficacy in patients with castration-resistant prostate
cancer. BACKGROUND: We evaluated the efficacy and safety of low-dose estramustine
phosphate (EMP) in Japanese patients with castration-resistant prostate cancer
(CRPC). PATIENTS AND METHODS: The present study was a single-arm, nonrandomized
prospective study in which all patients received EMP orally twice daily for a
total dose of 280 mg/day. A total of 31 patients with CRPC were enrolled from
December 2009 to December 2012 at 5 institutions in Japan. The primary endpoint
was the prostate-specific antigen (PSA) response, defined as a 50% decline in the
serum PSA level, confirmed >= 3 weeks later. The secondary endpoints included the
objective response rate, interval to PSA progression, PSA response duration,
progression-free survival, disease-specific survival, overall survival, safety,
and quality-of-life assessment using the Functional Assessment of Cancer Therapy
Prostate scores. RESULTS: Ten patients (32%) had a PSA response, and no patient
had an objective response. The treatment was well tolerated, and the most
frequent toxicities were grade 1 to 2 nausea/vomiting, anorexia, and
gynecomastia. The median interval to PSA progression was 140 days (95% confidence
interval [CI], 117-260 days). The PSA response duration was 119 days (95% CI, 49
219 days). The median progression-free survival was 213 days (95% CI, 167-422
days). The 3-year disease-specific survival and overall survival rates were 68.6%
(median not reached; 95% CI, 33 months to not available) and 59.9% (median 42
months, 95% CI, 28 months to not available), respectively. CONCLUSION: Low-dose
EMP seems to be a safe treatment option with some efficacy in patients with CRPC.
PMID- 26433629
TI - Geographical variation in relative risks associated with heat: Update of Spain's
Heat Wave Prevention Plan.
AB - A decade after the implementation of prevention plans designed to minimise the
impact of high temperatures on health, some countries have decided to update
these plans in order to improve the weakness detected in these ten years of
operation. In the case of Spain, this update has fundamentally consisted of
changing the so-called "threshold" or "trigger" temperatures used to activate the
plan, by switching from temperature values based on climatological criteria to
others obtained by epidemiological studies conducted on a provincial scale. This
study reports the results of these "trigger" temperatures for each of Spain's 52
provincial capitals, as well as the impact of heat on mortality by reference to
the relative risks (RRs) and attributable risks (ARs) calculated for natural as
well as circulatory and respiratory causes. The results obtained for threshold
temperatures and RRs show a more uniform behaviour pattern than those obtained
using temperature values based on climatological criteria; plus a clear decrease
in RRs of heat-associated mortality due to the three causes considered, at both a
provincial and regional level as well as for Spain as a whole. The updating of
prevention plans is regarded as crucial for optimising the operation of these
plans in terms of reducing the effect of high temperatures on population health.
PMID- 26433630
TI - Design, synthesis and antibacterial study of new potent and selective coumarin
chalcone derivatives for the treatment of tenacibaculosis.
AB - With the aim of finding new chemical entities selective for fish pathogens to
avoid drug resistance in humans, a series of coumarin-chalcone hybrid compounds
with different patterns of substitution were designed and synthesized. Their
antibacterial activity was evaluated against important types of human bacteria
strains (Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa) and
against a fourteen strains of the marine pathogen Tenacibaculum maritimum,
responsible for tenacibaculosis in fish, which is an important disease that
causes great economical loss in the aquaculture industry. All the amino
derivatives 5-12 presented high activity against different strains of T.
maritimum, no activity against any of the three human pathogenic bacteria strains
and no toxicity. Compounds 6, 7 and 11 were the most promising molecules. The
most sensitive strains to these compounds were LL01 8.3.8 and LL01 8.3.1, being
compound 11 up to 20 times more active than enrofloxacin. Therefore these
scaffolds are good candidates for aquaculture treatments, avoiding possible drug
resistance problems in humans.
PMID- 26433631
TI - Antihyperlipidemic morpholine derivatives with antioxidant activity: An
investigation of the aromatic substitution.
AB - Drugs affecting more than one target could result in a more efficient treatment
of multifactorial diseases as well as fewer safety concerns, compared to a one
drug one-target approach. Within our continued efforts towards the design of
multifunctional molecules against atherosclerosis, we hereby report the synthesis
of 17 new morpholine derivatives which structurally vary in terms of the aromatic
substitution on the morpholine ring. These derivatives simultaneously suppress
cholesterol biosynthesis through SQS inhibition (IC50 values of the most active
compounds are between 0.7 and 5.5 MUM) while exhibiting a significant protection
of hepatic microsomal membranes against lipid peroxidation (with IC50 values for
the most active compounds being between 73 and 200 MUM). Further evaluation of
these compounds was accomplished in vivo in an animal model of acute experimental
hyperlipidemia, where it was observed that compounds reduced the examined
lipidemic parameters (TC, TG and LDL) by 15-80%. In order to examine the mode of
binding of these molecules in the active catalytic site of SQS, we also performed
docking simulation studies. Our results indicate that some of the new compounds
can be considered interesting structures in the search for new multifunctional
agents of potential application in atherosclerosis.
PMID- 26433632
TI - Still shimming or already measuring?--Quantitative reaction monitoring for small
molecules on the sub minute timescale by NMR.
AB - In order to enable monitoring of rapidly occurring reactions Wagner et al.
recently presented a simple scheme for 1D NMR experiments with continuous data
acquisition, without inter-scan delays, using a spatially-selective and frequency
shifted excitation approach (Wagner et al., 2013). This scheme allows acquisition
of proton spectra with temporal resolutions on the millisecond timescale. Such
high temporal resolutions are desired in the case of reaction monitoring using
stopped flow setups. In regular (1)H NMR-spectra without spatial selection the
line width increases for a given shim setting with changes in sample volume,
susceptibility, convection and temperature or concentration gradients due to the
disturbance of magnetic field homogeneity. Concerning reaction monitoring this is
unfortunate as shimming prior to acquisition becomes necessary to obtain narrow
signals after injection of a reactant into an NMR sample. Even automatic shim
routines may last up to minutes. Thus fast reactions can hardly be monitored
online without large hardware dead times in a single stopped flow experiment.
This problem is reduced in the spatially-selective and frequency-shifted
continuous NMR experiment as magnetic field inhomogeneties are less pronounced
and negative effects on the obtained line shapes are reduced as pointed out by
Bax and Freeman (1980) [2] and demonstrated by Wagner et al. (2013). Here we
present the utilization of this technique for observation of reactions in small
molecule systems in which chemical conversion and longitudinal relaxation occur
on the same timescale. By means of the alkaline ethyl acetate hydrolysis, a
stoichiometric reaction, we show advantages of spatially-selective excitation on
both temporal resolution and line shapes in stopped flow experiments. Results are
compared to data obtained by non-selective small angle excitation experiments.
PMID- 26433633
TI - Off-pump coronary artery bypass grafting improves short-term outcomes in high
risk patients compared with on-pump coronary artery bypass grafting: Meta
analysis.
AB - OBJECTIVES: To assess the benefits and risks of off-pump coronary artery bypass
(OPCAB) versus coronary artery bypass grafting (CABG) through a meta-analysis of
randomized controlled trials (RCTs), and to investigate the relationship between
outcomes and patient risk profile. METHODS: PubMed, Embase, the Cumulative Index
of Nursing and Allied Health Literature, Scopus, Web of Science, Cochrane
Library, and major conference proceedings databases were searched for RCTs
comparing OPCAB and CABG and reporting short-term (<= 30 days) outcomes.
Endpoints assessed were all-cause mortality, myocardial infarction (MI), and
cerebral stroke. RESULTS: The meta-analysis included 100 studies, with a total of
19,192 subjects. There was no difference between the 2 techniques with respect to
all-cause mortality and MI (odds ratio [OR], 0.88; 95% confidence interval [CI],
0.71-1.09; P = .25; I(2) = 0% and OR, 0.90; 95% CI, 0.77-1.05; P = .19; I(2) =
0%, respectively). OPCAB was associated with a significant 28% reduction in the
odds of cerebral stroke (OR, 0.72; 95% CI, 0.56-0.92; P = .009; I(2) = 0%). A
significant relationship between patient risk profile and benefits from OPCAB was
found in terms of all-cause mortality (P < .01), MI (P < .01), and cerebral
stroke (P < .01). CONCLUSIONS: OPCAB is associated with a significant reduction
in the odds of cerebral stroke compared with conventional CABG. In addition,
benefits of OPCAB in terms of death, MI, and cerebral stroke are significantly
related to patient risk profile, suggesting that OPCAB should be strongly
considered in high-risk patients.
PMID- 26433634
TI - Discussion.
PMID- 26433635
TI - Prophylactic stage 1 elephant trunk for moderately dilated descending aorta in
patients with predominantly proximal disease.
AB - OBJECTIVE: Staged elephant trunk (ET) repair is a commonly performed procedure
for extensive aortic disease. A significant proportion of patients with
predominantly proximal aortic pathology often have in addition a moderately
dilated descending aorta (<5 cm) that can progress over time. Objectives were to
characterize patients, determine completion rate after prophylactic stage 1 ET,
and assess outcomes. METHODS: From 1992 to 2012, a total of 572 patients
underwent stage 1 ET for degenerative aneurysm and dissection at Cleveland
Clinic. Prophylactic stage 1 ET was performed in 117 (20.5%) who had
predominantly proximal disease (5.5 +/- 1 cm) with moderate dilation of the
descending aorta (4 +/- 0.6 cm). Aortic pathology included: aneurysm (n = 56
[48%]); chronic dissection (n = 41 [35%]); pseudoaneurysm (n = 9 [7.7%]);
penetrating ulcer (n = 9 [7.7%]); and intramural hematoma (n = 2 [1.7%]). Other
diagnoses included connective tissue disorder (12 [10%]); aortitis (20 [17%]);
bicuspid aortic valve (9 [7.6%]); and previous type A dissection repair (27
[23%]). RESULTS: Operative mortality was 0.8% (1 of 117). This patient suffered
postoperative myocardial infarction and mesenteric ischemia, resulting in sepsis
and death. Other complications included: stroke (n = 7 [6%]); tracheostomy (n = 6
[5%]); renal dialysis (n = 4 [3.3%]); and reoperation for bleeding (n = 7 [6%]).
The mean follow-up time was 4 +/- 3 years. Fifty-three (45%) patients completed
the stage 2 ET (open: 20 [38%]; endovascular: 33 [62%]) at a median interval of 6
months (9 days-10 years). The mean descending diameter increased from 4.1 +/- 0.6
cm to 5 +/- 1 cm at the time of stage 2 completion. In 11 patients, stage 2 was
performed for acute aortic events. Estimated survival at 1, 5, and 8 years was
94%, 88%, and 74%, respectively. CONCLUSIONS: Prophylactic ET for moderately
dilated descending aorta is an effective strategy for staged repair, especially
in patients with chronic dissection, connective tissue disorder, and aortitis. In
addition, this approach can be beneficial for emergency treatment of late distal
aortic complications.
PMID- 26433636
TI - Light response and potential interacting proteins of a grape flavonoid 3'
hydroxylase gene promoter.
AB - Flavonoid 3'-hydroxylase (F3'H), a member of cytochrome P450 protein family,
introduces B-ring hydroxyl group in the 3' position of the flavonoid. In this
study, the cDNA sequence of a F3'H gene (VviF3'H), which contains an open reading
frame of 1530 bp encoding a polypeptide of 509 amino acids, was cloned and
characterized from Vitis vinifera L. cv. Cabernet Sauvignon. VviF3'H showed high
homology to known F3'H genes, especially F3'Hs from the V. vinifera reference
genome (Pinot Noir) and lotus. Expression profiling analysis using real-time PCR
revealed that VviF3'H was ubiquitously expressed in all tested tissues including
berries, leaves, flowers, roots, stems and tendrils, suggesting its important
physiological role in plant growth and development. Moreover, the transcript
level of VviF3'H gene in grape berries was relatively higher at early
developmental stages and gradually decreased during veraison, and then increased
in the mature phase. In addition, the promoter of VviF3'H was isolated by using
TAIL-PCR. Yeast one-hybrid screening of the Cabernet Sauvignon cDNA library and
subsequent in vivo/vitro validations revealed the interaction between VviF3'H
promoter and several transcription factors, including members of HD-Zip, NAC, MYB
and EIN families. A transcriptional regulation mechanism of VviF3'H expression is
proposed for the first time.
PMID- 26433637
TI - The effect of cryptogein with changed abilities to transfer sterols and altered
charge distribution on extracellular alkalinization, ROS and NO generation, lipid
peroxidation and LOX gene transcription in Nicotiana tabacum.
AB - Cryptogein, a protein from oomycete Phytophthora cryptogea, induces a
hypersensitive cell death in Nicotiana tabacum. We prepared a new series of
cryptogein mutant proteins with altered abilities to bind sterols and with
altered charge distribution in the proteins. The effect of the mutations on the
cryptogein ability to induce plant defence mechanisms associated with
hypersensitive cell death were examined. Our results with new mutants support the
previous findings that the sterol binding does not influence synthesis of ROS,
cytosol acidification and development of leaf necrosis as these events seem to be
more likely affected by the charge distribution and the overall protein
structure. This hypothesis was also applicable on other mechanisms involved in
the execution of plant cell death such as the NO generation, the stimulation of
lipid peroxidation (determination of malondialdehyde and hydroxy fatty acids
levels) and LOX gene transcription. In addition, the ability to bind sterols was
found to serve not only for pathogen utilisation in its own metabolism but also
to have an important function for the destabilization of plant membrane
facilitating the pathogen spread inside the plant tissue as well as intensively
contributing to the development of plant cell death. Considering the insertion of
charged amino acid residues in the protein structure, the change localized in the
protein surface affected its biological activity more effectively than that
change inside the protein cavity. Moreover, the insertion of negative charged
amino acids influenced mainly the events involved in the early phase of defence
reaction, while the positive residues affected especially the necrotic activity
of cryptogein.
PMID- 26433638
TI - Visual field asymmetries in object individuation.
AB - Repetition blindness (RB) is a failure to detect both instances of two identical
stimuli presented in close temporal proximity. It is due to an inability to form
separate episodic tokens for a repeated stimulus, resulting in a single conscious
representation. In three experiments, participants identified two targets
presented simultaneously in different spatial locations. These stimuli were
either the same or different. In two experiments the targets occurred on either
side of fixation, and in a third experiment both were in the same hemifield. In
all experiments, RB was more pronounced for stimuli in the right hemifield. In
addition, there was a left hemifield advantage for both repeated and non-repeated
stimuli when the two stimuli occurred in opposite visual fields and, thus, were
processed by different hemispheres. These findings suggest that the right
hemisphere plays a dominant role in attentional selection and in creating
conscious representations of visual events.
PMID- 26433639
TI - Turning I into me: Imagining your future self.
AB - A widely endorsed belief is that perceivers imagine their present selves using a
different representational format than imagining their future selves (i.e., near
future=first-person; distant future=third-person). But is this really the case?
Responding to the paucity of work on this topic, here we considered how temporal
distance influences the extent to which individuals direct their attention
outward or inward during a brief imaginary episode. Using a non-verbal measure of
visual perspective taking (i.e., letter-drawing task) our results confirmed the
hypothesized relation between temporal distance and conceptions of the self.
Whereas simulations of an event in the near future were dominated by a first
person representation of the self, this switched to a third-person depiction when
the event was located in the distant future. Critically, this switch in vantage
point was restricted to self-related simulations. The theoretical and practical
implications of these findings are considered.
PMID- 26433640
TI - Reply to: Assessment of pouch and stoma size in weight loss failure after Roux-en
Y gastric bypass.
PMID- 26433641
TI - Internal hernia after revisional laparoscopic loop duodenal switch surgery.
PMID- 26433642
TI - Lengthening of the biliopancreatic limb is a key step during revisional Roux-en-Y
gastric bypass for weight regain and diabetes recurrence.
PMID- 26433643
TI - Comment on: Comprehensive evaluation of the effect of bariatric surgery on pelvic
floor disorders.
PMID- 26433644
TI - Water-insoluble sericin/beta-cyclodextrin/PVA composite electrospun nanofibers as
effective adsorbents towards methylene blue.
AB - A novel water-insoluble sericin/beta-cyclodextrin/poly (vinyl alcohol) composite
nanofiber adsorbent was prepared by electrospinning and followed by thermal
crosslinking for removal of cationic dye methylene blue from aqueous solution.
Fourier transform infrared spectroscopy and solubility experiments confirmed that
sericin and beta-cyclodextrin were incorporated into the nanofibers and the
crosslinking reaction occurred successfully. Kinetics, isotherms and
thermodynamics analysis were studied for adsorption of methylene blue. The
adsorption process is better fitted with the pseudo-second-order model and
Langmuir isotherm model. The maximum adsorption capacities are 187.97, 229.89,
and 261.10mg/g at the temperatures 293, 313 and 333 K, respectively.
Thermodynamic parameters showed that methylene blue adsorption was endothermic
and spontaneous. In addition, the fiber membrane adsorbent could be easily
separated from dye solution and showed high recyclable removal efficiency. All
these results suggest that crosslinked sericin/beta-cyclodextrin/poly(vinyl
alcohol) composite nanofibers could be potential recyclable adsorbents in dye
wastewater treatment.
PMID- 26433645
TI - Enhanced toxicity and cellular uptake of methotrexate-conjugated nanoparticles in
folate receptor-positive cancer cells by decorating with folic acid-conjugated d
alpha-tocopheryl polyethylene glycol 1000 succinate.
AB - Folic acid-conjugated d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS
FOL) decorated methotrexate (MTX)-conjugated nanoparticles were developed for
targeted delivery of MTX to folate receptor-expressed tumor cells. The synthesis
of TPGS-FOL followed 3-step process. Firstly, the terminal hydroxyl group of TPGS
was converted to sulfonyl chloride using mesyl chloride in comparison with nosyl
and tosyl chlorides. The highest conversion efficiency and yield were obtained by
mesyl chloride due to the formation of higher reactive intermediate in a presence
of triethylamine. Secondly, the substitution of sulfonyl group by sodium azide
produced considerably high yield with conversion efficiency of over 90%. Lastly,
the coupling reaction of azido-substituted TPGS and propargyl folamide by click
reaction resulted in 96% conjugation efficiency without polymer degradation. To
fabricate the folate receptor-targeted nanoparticles, 10 and 20%mol MTX
conjugated PEGylated poly(epsilon-caprolactone) nanoparticles were decorated with
TPGS-FOL. The size and size distribution of MTX-conjugated nanoparticles
relatively increased with %MTX. The MTX release from the nanoparticles was
accelerated in acidic medium with an increase of %MTX but retarded in
physiological pH medium. The decoration of TPGS-FOL onto the nanoparticles
slightly enlarged the size and size distribution of the nanoparticles; however,
it did not affect the surface charge. The cytotoxicity and cellular uptake of MCF
7 cells demonstrated that 10% MTX-conjugated nanoparticles and FOL-decorated
nanoparticles possessed higher toxicity and uptake efficiency than 20% MTX
conjugated nanoparticles and undecorated nanoparticles, respectively. The results
indicated that FOL-10% MTX-conjugated nanoparticles exhibited potential targeted
delivery of MTX to folate receptor-expressed cancer cells.
PMID- 26433646
TI - Bioengineered neo-corneal endothelium using collagen type-I coated silk fibroin
film.
AB - Corneal transplantation, a common surgical protocol for visual acuity
improvement, is limited owing to shortage of high quality donor corneas and/or
lack of accurate replication of structural and biochemical composition of native
cornea in a scaffold. Construction of neo-corneas utilizing novel, biocompatible
and biodegradable scaffold/film source, could possibly address such formidable
challenges. Herein, we designed optically transparent, micro-structurally stable
silk films surface-coated with collagen type-I (Col-I/SF) as an alternative
scaffold source for bioengineering of neo-cornea. Morphological, structural
characteristics and in vitro biological studies were performed using primary
rabbit corneal endothelial cells (rCEnCs) as models. The Col-I/SF films
demonstrated higher Ra (nm) values compared to the bare SF surfaces. In vitro
biological studies showed a significant increment in initial cell attachment and
proliferation of cultured rCEnCs on the Col-I/SF films with well-maintained
characteristic polygonal shape of rCEnCs. Although any remarkable changes
regarding the morphology, expression of ZO-1 and Na(+)/K(+)-ATPase were absent,
however the cells were found to be capable of well-expressing their functional
proteins which regulates functions of corneal endothelium. Collectively, these
results strongly suggest Col-I/SF film for future corneal transplantation
therapy.
PMID- 26433647
TI - Favourable attitudes towards serosorting are associated with overall less
frequent condom use among young Black men having sex men.
AB - This study determined whether YBMSM endorsing serosorting are less likely to use
condoms. A questionnaire assessed men's attitudes towards serosorting with a
three-item scale; various sexual risk behaviours were measured using a 90-day
recall period. Favourable attitudes toward serosorting were associated with a
greater likelihood of condomless sex as a top (P<0.001) and as a bottom
(P<0.001), as well as a lower likelihood of using condoms with main partners
(P=0.003). Findings suggest that YBMSM having favourable attitudes toward
serosorting may be more likely to report condomless sex than their counterparts
without favourable attitudes.
PMID- 26433648
TI - DAC-EuCheMS Lecture Award presented to ABC Advisory Board Member Miguel
Valcarcel.
PMID- 26433651
TI - Diuretic and antioxidant activities of the aqueous extract of leaves of Cassia
occidentalis (Linn.) in rats.
AB - OBJECTIVE: To assess the putative diuretic and antioxidant properties of Cassia
occidentalis (C. occidentalis) leaves' aqueous extract. METHODS: Adult rats were
administered with C. occidentalis leaves aqueous extract acutely (24 h) and
subchronically (7 d), at doses 80, 160, 240, 320, and 400 mg/kg (per os).
Negative control group received only an equivalent volume of distilled water,
while the two positive control groups received the diuretic drugs furosemide (20
mg/kg, ip.) and hydrochlorothiazide (HCTZ) (20 mg/kg, ip.). Urinary elimination
of electrolytes in response to treatments was evaluated, together with changes in
concentrations of creatinine, urea, aldosterone, glucose, and albumin in urine
and plasma. Various urinary indicators of kidney function and plasmatic markers
of oxidative stress were also assessed. RESULTS: The acute administration of C.
occidentalis increased the urinary excretion of 107.58% at the higher dose
tested, compared to negative control. The reference drugs furosemide and HCTZ
induced increases of 84.27% and 48.05%, respectively. Acutely, the extract
induced Na(+) and Cl(-) elimination, whereas subchronically an increase in K(+)
elimination was also observed. The extract also improved the kidney function
indexes and oxidative stress markers. These effects were dose-dependent and
comparable with positive control observations. CONCLUSIONS: Our findings strongly
suggest that C. occidentalis aqueous extract has diuretic and antioxidant
activities, and deserves further studies considering the potential for the
treatment of hypertension.
PMID- 26433649
TI - Performing a hepatic timing signal: glucocorticoids induce gper1a and gper1b
expression and repress gclock1a and gbmal1a in the liver of goldfish.
AB - Glucocorticoids have been recently proposed as input signals of circadian system,
although the underlying molecular mechanism remains unclear. This work
investigates the role of glucocorticoids as modulators of clock genes expression
in the liver of goldfish. In fish maintained under a 12L:12D photoperiod, an
intraperitoneal injection at Zeitgeber Time 2 of a glucocorticoid analog,
dexamethasone (1 MUg/g body weight) induced per1 genes while decreased gbmal1a
and gclock1a expression in the liver at 8 h post-injection. A 4-h in vitro
exposure of goldfish liver to cortisol (0.1-10 MUM) also induced gper1 genes in a
concentration-dependent manner. Similarly, the exposure of the goldfish cultured
liver to dexamethasone produced a concentration-dependent induction of gper1
genes. Moreover, this glucocorticoid analog led to a decrease in gbmal1a and
gclock1a transcripts, while the other clock genes analyzed were unaffected. The
induction of gper1a and gper1b by dexamethasone in vitro was observed at short
times (2 h), whereas the reductions of gbmal1a and gclock1a transcripts needed
longer exposure times (8 h) to the glucocorticoid to be significant.
Additionally, a 2-h exposure to dexamethasone in the liver culture was enough to
extend the induction of per genes for more than 12 h. Present results indicate
that gper1 genes are targets for glucocorticoids in the regulation of goldfish
hepatic oscillator, as previously reported in mammals, suggesting a conserved
role of glucocorticoids in the functional organization of the peripheral
circadian system in vertebrates. The repression of clock1a and bmal1a is not so
well established, and suggests that other clock genes could be glucocorticoid
targets in the goldfish liver.
PMID- 26433650
TI - Peroxiredoxin 6 from the Antarctic emerald rockcod: molecular characterization of
its response to warming.
AB - In the present study, we describe the purification and molecular characterization
of two peroxiredoxins (Prdxs), referred to as Prdx6A and Prdx6B, from Trematomus
bernacchii, a teleost widely distributed in many areas of Antarctica, that plays
a pivotal role in the Antarctic food chain. The two putative amino acid sequences
were compared with Prdx6 orthologs from other fish, highlighting a high
percentage of identity and similarity with the respective variant, in particular
for the residues that are essential for the characteristic peroxidase and
phospholipase activities of these enzymes. Phylogenetic analyses suggest the
appearance of the two prdx6 genes through a duplication event before the
speciation that led to the differentiation of fish families and that the
evolution of the two gene variants seems to proceed together with the evolution
of fish orders and families. The temporal expression of Prdx6 mRNA in response to
short-term thermal stress showed a general upregulation of prdx6b and inhibition
of prdx6a, suggesting that the latter is the variant most affected by temperature
increase. The variations of mRNA accumulation are more conspicuous in heart than
the liver, probably related to behavioral changes of the specimens in response to
elevated temperature. These data, together with the peculiar differences between
the molecular structures of the two Prdx6s in T. bernacchii as well as in the
tropical species Stegastes partitus, suggest an adaptation that allowed these
poikilothermic aquatic vertebrates to colonize very different environments,
characterized by different temperature ranges.
PMID- 26433652
TI - Chemical composition, mechanism of antibacterial action and antioxidant activity
of leaf essential oil of Forsythia koreana deciduous shrub.
AB - OBJECTIVE: To identify the chemical constituents of leaf essential oil of
Forsythia koreana (F. koreana) and evaluate its effects on bacterial strains.
METHODS: The essential oil of leaf of F. koreana was extracted by using
hydrodistillation process and the volatile components investigated with the help
of gas chromatography coupled with mass spectrometry. The antibacterial study was
carried out with the help of agar disc diffusion method, MIC, MBC and viable
count. The mode of action was determined with help of potassium ion flux,
cellular material release and scanning electron microscopy. The antioxidant
activity was determined with the help of 2, 3-diphenyl-2-picrylhydrazyl method,
nitric oxide scavenging activity and superoxide anion radical scavenging assay.
RESULTS: Total ten compounds were identified as trans-phytol (42.73%), cis-3
hexenol (12.95%), beta-linalool (10.68%), trans-2-hexenal (8.86%), trans-2
hexenol (8.86%), myrcenol (3.86%), 4-vinylphenyl acetate (3.86%), (4Z)-4,6
heptadien-1-ol (3.18%), lemonol (2.73%) and benzeneacetaldehyde (2.27%) by gas
chromatography coupled with mass spectrometry. The antibacterial study was
demonstrated that leaf essential oil of F. koreana act against foodborne and
other pathogenic bacteria. The mode of action revealed that this essential oil
acted on the cytoplasmic membrane, resulting in loss of integrity and increased
permeability. In addition, leaf essential oil of F. koreana was shown to be rich
in linalool, which contributes to improved antioxidant activity. CONCLUSIONS:
These results show that leaf essential oil of F. koreana has great potential as a
natural food preservative, antibacterial and antioxidant agent.
PMID- 26433653
TI - A pilot study of antioxidant potential of endophytic fungi from some Sudanese
medicinal plants.
AB - OBJECTIVE: To evaluate the total phenolic content and total antioxidant capacity
of ethyl acetate extracts of 21 endophytic fungi isolated from five Sudanese
medicinal plants: Calotropis procera, Catharanthus roseus, Euphorbia prostrate,
Vernonia amygdalina and Trigonella foenum-graecum. METHODS: Crude extracts of
endophytic fungi and their host plants were tested by classical Folin-Ciocalteu
colorimetric method to determine the total phenolic content, also total
antioxidant capacity was estimated using 1,1-diphenyl-2-picrylhydrazyl free
radical scavenging in vitro method. RESULTS: Among the endophytes, endophytic
fungus Aspergillus sp. from Trigonella foenum-graecum seeds demonstrated the
highest both total phenolic content in term of gallic acid equivalent [(89.9 +/-
7.1) mg GAE/g] and antioxidant activity for 1,1-diphenyl-2-picrylhydrazyl radical
scavenging assay [IC50: (18.0 +/- 0.1) MUg/mL]. A high positive linear
correlation (R(2) = 0.999 1) was found between total antioxidant capacity and
total phenolic content of endophytic fungi isolated from Vernonia amygdalina.
CONCLUSIONS: The present study revealed that some endophytic fungi from the five
Sudanese medicinal plants could be a potential source of novel natural
antioxidant compounds.
PMID- 26433654
TI - Prevalence of filarial parasites in domestic and stray cats in Selangor State,
Malaysia.
AB - OBJECTIVE: To determine the prevalence of the filarial parasites,ie.,Brugia
malayi, Brugia, Brugia pahangi(B. pahangi), Dirofilaria immitisandDirofilaria
repens (D. repens) in domestic and stray cats. METHODS: A total of 170 blood
sample were collected from domestic and stray cats and examined for filarial worm
parasites in two localities, Pulau Carey and Bukit Gasing, Selangor State,
Malaysia. RESULTS: The overall prevalence of infection was 23.5% (40/170; 95% CI
= 17.4-30.6). Of this, 35% (14/40; 95% CI = 22.1-50.5) and 50% (20/40; 95% CI =
35.2-64.8) were positive for single B. pahangi nd D. repens, respectively. The
remaining of 15% (6/40; 95% CI = 7.1-29.1) were positive for mixed B. pahangi and
D. repens. In addition, 75% of the infected cats were domestic, and 25% were
strays. No Brugia malayi and Dirofilaria immitis was detected. Eighty-four cats
were captured at Pulau Carey, of which 35.7% (30/84) were infected. Among the
cats determined to be infected, 93% (28/30; 95% CI = 78.7-98.2) were domestic,
and only 6.7% (2/30; 95% CI = 19.0-21.3) were strays. Conversely, the number of
infected cats was three times lower in Bukit Gasing than in Pulau Carey, and most
of the cats were stray. CONCLUSIONS: B. pahangi and D. repens could be the major
parasites underlying filariasis in the study area. Adequate prophylactic plans
should be administrated in the cat population in study area.
PMID- 26433655
TI - Genetic variation of Leptospira isolated from rats catched in Yogyakarta
Indonesia.
AB - OBJECTIVE: To detect genetic variations among pathogenic Leptospira isolated from
rats using 16S rRNA gen as chronometer. METHODS: This is an observational study
with cross sectional design. Rats samples were taken in Yogyakarta Special Region
of Indonesia. Leptospira in the rats was detected by two methods i.e. real time
PCR (qPCR) by using primers correspond to16S rRNA gene of Leptospira, and
standard PCR by using different set of primer correspond to the 16S rRNA gene of
Leptospira. The standard PCR amplicon then subjected for DNA sequencing. Analysis
genetic variation was performed using MEGA 6.2. Software. RESULTS: There were 99
DNA samples from rats included in this study. Detection of Leptospira by using
qPCR revealed 25 samples positive for pathogenic Leptospira, while only 6 samples
were able to be detected using standard PCR. The new primer set correspond to 16S
rRNA gene was able to detect specifically pathogenic Leptospira in the rats.
Sequencing analysis of 6 PCR amplicons showed that the Leptospira which infect
the rats catched in Yogyakarta genetically close related with pathogenic
Leptospira which were isolated from human, animal, rodents, and environment.
CONCLUSIONS: It can be considered that rats are the most important vector and
reservoir of Leptospira.
PMID- 26433657
TI - Epidemiology of influenza viruses from 2009 to 2013 - A sentinel surveillance
report from Union territory of Puducherry, India.
AB - OBJECTIVE: To report the findings of influenza surveillance programme from Union
territory of Puducherry and to document the clinical and epidemiological data of
influenza viruses over a five year period from 2009 to 2013. METHODS: Respiratory
samples were collected from patients with influenza-like illness from 2009 to
2013 as part of routine diagnostic and surveillance activity. Detection of
pandemic influenza A (H1N1) 2009, influenza A (H3N2) and influenza B was done
using Real-time PCR. RESULTS: Of the total 2247 samples collected from patients
with influenza-like illness during the study period 287 (12.7%) and 92 (4.0%)
were positive for influenza A (H1N1) 2009 and influenza A (H3N2) respectively. A
subset of 557 of these samples were also tested for influenza B and 24 (4.3%)
were positive. Significantly higher positivity rate for both viruses was observed
in adults when compared with children. The peak positivity of influenza A (H1N1)
2009 was observed in 2009 followed by 2012, while that of influenza A (H3N2) was
more uniformly distributed with the exception of 2012. Overall mortality rate due
to influenza A (H1N1) 2009 was 7.6% while it was 1% for influenza A (H3N2). Each
year influenza-like illness and influenza virus activity coincided with period of
high rainfall and low temperature except in the first half of 2012. CONCLUSIONS:
As the sole referral laboratory in this region, the data provides a comprehensive
picture of influenza activity. This information will be useful in future planning
of the vaccine schedule and influenza pandemic preparedness.
PMID- 26433656
TI - Molecular survey of tick-borne pathogens in Ixodid ticks collected from hunted
wild animals in Tuscany, Italy.
AB - OBJECTIVE: To determine the prevalence of zoonotic tick-borne bacteria in feeding
ticks removed from hunted wild animals. METHODS: PCR was executed on DNA
extracted from 77 tick pools to detect Anaplasma phagocytophilum, Bartonella
spp., Borrelia burgdorferi sensu lato, Coxiella burnetii and Rickettsia spp.
RESULTS: A total of 432 ticks were collected: 30 (6.94%) Haemaphysalis punctata,
72 (16.7%) Dermacentor marginatus and 330 (76.38%) Ixodes ricinus. For each
animal one or two pools of 3 ticks of the same species was constituted. Seventy
seven tick pools were examined by PCR: 58 (75.32%) resulted infected and among
them 14 (18.18%) showed co-infections. In particular, 29 (37.66%) pools were
positive for Bartonella spp., 23 (29.87%) for Anaplasma phagocytophilum, 16
(20.78%) for Rickettsia spp., and 5 (6.49%) for Borrelia burgdorferi s.l. All
samples were negative for Coxiella burnetii. CONCLUSIONS: The results demonstrate
the presence of several zoonotic tick-borne pathogens in the studied area, and
underline the risk of exposure to infections for hunters not only during the
outdoor activity, but also when they manipulate hunted animals infested by
infected ticks.
PMID- 26433658
TI - Effect of BRMS1 expression on proliferation, migration and adhesion of mouse
forestomach carcinoma.
AB - OBJECTIVE: To discuss the effect of BRMS1 on the proliferation, migration and
adhesion of mouse forestomach carcinoma. METHODS: The constructed pCMV-myc-BRMS1
recombinant plasmid and blank plasmid were transfected into mouse forestomach
carcinoma. MTT method was employed to measure the activity of gastric cancer
cell; the scratch assay and Transwell assay to measure the migration and invasion
of gastric cancer cell; the adhesion assay to measure the adhesion of gastric
cancer cell; while the Western blot assay to measure the expression of The NF
kappaB signal pathway, downstream matrix metalloproteinase (MMP)-2, MMP-9 and
osteopontin and E-cadherin in the gastric cancer cell. Besides, the transplanted
animal model of gastric cancer in mice was constructed to measure the size of
tumor xenograft. RESULTS: Results of MTT assay showed that, compared with the
empty vector control group, the activity of gastric cancer cell was not affected
in the BRMS1 transfection group. The improved expression of BRMS1 could inhibit
the adhesion, migration and invasion of gastric cancer cell (P < 0.01). Besides,
compared with the empty vector control group, the phosphorylation of NF-kappaB
p65 and IkappaBalpha was reduced in the BRMS1 transfection group, with the
decreased expression of MMP-2, MMP-9 and osteopontin and the increased expression
of E-cadherin (P < 0.01). Results of animal experiment also showed that the
expression of BRMS1 did not affect the transplanted tumor. CONCLUSIONS: The
expression of BRMS1 can significantly inhibit the adhesion, migration, invasion
and metastasis of mouse forestomach carcinoma gastric cancer cell, which is
related to The NF-kappaB signal pathway.
PMID- 26433659
TI - Effect of PI3K-mediated autophagy in human osteosarcoma MG63 cells on sensitivity
to chemotherapy with cisplatin.
AB - OBJECTIVE: To investigate the influence of autophagy on sensitivity to the
chemotherapy drug cisplatin (DDP) and the role of PI3K in autophagy. METHODS: MTT
methods and flow cytometer, with rapamycin up-regulating the autophagy and 3-MA
down-regulating the autophagy, were employed to measure the proliferation
inhibition rate on DDP-treated osteosarcoma cells and the change in cell cycle.
The expression of intracellular protein was detected by Western blot. The
autophagy of MG63 cell was observed using fluorescence microscope and
transmission electron microscope. RESULTS: Western blot showed that basic
autophagy level of MG63 cell was significantly lower than that of hFOB cell. MTT
test revealed that the cell proliferation inhibition rate in the group treated
with rapamycin and DDP, group treated with 3-MA and DDP, and group only treated
with DDP was significantly different. It was demonstrated by the flow cytometry
that in group treated with DDP, inhibition on autophagy can increase the cell
numbers in G1 phase and reduce the cell numbers in S phase of cell cycle.
Increase of autophagosome in MG63 cytoplasm was observed under fluorescence
microscope. CONCLUSIONS: Up-regulating the autophagy significantly reduced the
sensitivity of MG63 cell to chemotherapy with DDP. DDP induced autophagy of MG63
cell and blocked the cell cycle at G1 phase.
PMID- 26433660
TI - Comparative analysis of biological characteristics of adult mesenchymal stem
cells with different tissue origins.
AB - OBJECTIVE: To invest the differences among mesenchymal stem cells (MSCs) derived
from different tissues and their impacts on clinical applications. METHODS: In
this study, MSCs were isolated from adipose tissue (AD), umbilical cord tissue
(UC), and menstrual blood (Men) and compared their biological characteristics in
terms of proliferation capacity, passage capacity, colony formation, and surface
markers were compared. RESULTS: The stem cells (SCs) obtained from different
sources were all characterized as MSCs, but demonstrated some differences.
Umbilical cord-derived MSCs (UCMSCs) were able to overcome density inhibition.
The proliferation rate decreased in the order UCMSCs > MenSCs > ADSCs, while the
colony-forming ability decreased in the order MenSCs > ADSCs > UCMSCs. Based on
gene-expression data for MSCs from different sources within the same donor, 768
MenSC genes were found that were specifically upregulated or downregulated
compared with bone marrow-derived MSCs and UCMSCs, most of which were involved in
cell function-related pathways. In addition, MenSCs appeared to be superior in
terms of immune inflammation, stress response, and neural differentiation
potentials, but weaker in terms of osteogenic and chondrogenic differentiation
capacities, compared with UCMSCs and bone marrow-derived MSCs. CONCLUSIONS:
MenSCs have higher extraction efficiency, colony-forming ability, and long time
passage capacity. Although the proliferation capacity is inferior to UCMSCs.
PMID- 26433661
TI - Effect of microRNA-208a on mitochondrial apoptosis of cardiomyocytes of neonatal
rats.
AB - OBJECTIVE: To explore the effect and mechanism of microRNA-208a (miR-208a) in the
mitochondrial apoptosis of cardiomyocytes of neonatal rats. METHODS: The primary
cultured cardiomyocytes of neonatal rats were added into the hypoxia incubator
for the hypoxia induction. The overexpression system for miR-208a of
cardiomyocytes of neonatal rats was built. The flow cytometry assay was employed
to detect the incidence of apoptosis in the over-expressed miR-208a. The
mitochondrial staining technique was used to detect the change in the
mitochondrial morphology of over-expressed miR-208a. The bioinformatic analysis
was chosen to analyze and predict the target gene of miR-208a. RESULTS: Firstly,
the primary culture system of cardiomyocytes of neonatal rats was successfully
built. The miR-208a was over-expressed in cardiomyocytes of neonatal rats by miR
208a Mimics. Results of flow cytometry assay showed that the over-expressed miR
208a could significantly reduce the incidence of apoptosis; while results of
mitochondrial staining indicated the change in the mitochondrial morphology of
over-expressed miR-208a and the mitochondrial fission process was inhibited. In
conclusion, it was supposed that miR-208a could inhibit the activation of
mitochondrial fission process to keep the cardiomyocytes from apoptosis.
CONCLUSIONS: The over-expressed miR-208a can reduce the incidence of apoptosis in
the cardiomyocytes of neonatal rats, significantly change the mitochondrial
morphology and inhibit the mitochondrial fission process.
PMID- 26433662
TI - Clinical significance of microRNA-130b in osteosarcoma and in cell growth and
invasion.
AB - OBJECTIVE: To investigate clinical significance of microRNA-130b (miR-130b) in
osteosarcoma and its role in cell growth and invasion. METHODS: miR-130b
expression was detected in 68 samples of surgically resected osteosarcoma and
matched normal tumor-adjacent tissues by qRT-PCR. The expression of miR-130b was
altered by corresponding vectors in osteosarcoma cells, and then Western blot was
used to detect the expression of PPARgamma. BrdU cell proliferation and Transwell
assays were performed to determine cell proliferation and invasion. RESULTS: The
expression of miR-130b in osteosarcoma tissues was significantly higher than that
in normal tumor-adjacent tissues. Its expression in patients with metastasis was
significantly higher than that in those without metastases. miR-130b expression
in tumor tissues was significantly associated with tumor size, clinical stage and
distant metastasis. And its expression was significantly correlated with overall
survival and disease free survival. miR-130b overexpression obviously repressed
the expression of PPARgamma, and resulted in significant increase of Saos-2 cell
proliferation and invasion. On the contrast, repressing miR-130b expression with
its inhibitor significantly increased PPARgamma expression, and inhibited MG-63
cell proliferation and invasion. CONCLUSIONS: The high-expression of miR-130b is
correlated with the adverse clinicopathological features and poor prognosis in
osteosarcoma. miR-130b may regulate proliferation and invasion of osteosarcoma
cells by targeting PPARgamma, suggesting miR-130b may play a key role in the
progression of osteosarcoma.
PMID- 26433663
TI - Anti-proliferation and radiosensitization effects of chitooligosaccharides on
human lung cancer line HepG2.
AB - OBJECTIVE: To observe the anti-proliferation and radiosensitization effect of
chitooligosaccharides (COS) on human lung cancer cell line HepG2. METHODS: CCK-8
assay was employed to obtain the inhibition ratio of COS on HepG2 cells at 24 h
after treatment. The clonogenic assay was used to analyze the cell viability of
RAY group and RAY + COS group with X-ray of 0, 1, 2, 4, 6 and 8 Gy, and the cell
survival curve was used to analyze the sensitization ratio of COS. Flow cytometry
was employed to detect cell cycle and apoptosis rate in control group, RAY group
and RAY + COS group after 24 h treatment. RESULTS: COS inhibited the
proliferation of HepG2 cells, and the inhibition rate positively correlated with
the concentration of COS. The cell viability decreased with increasing exposure
dose in RAY group and RAY + COS group. The cell viabilities of RAY + COS group
were lower than those of RAY group at the dose of 4, 6 and 8 Gy (P < 0.05), and
the sensitization ratio of COS was 1.19. There were higher percentage at G2/M
phase and apoptosis rate, and lower percentage at S phase in RAY + COS group
versus the other two groups (P < 0.01). CONCLUSIONS: COS can inhibit the
proliferation of HepG2 cells, and enhance the radiosensitization of HepG2 cells,
induce apoptosis and G2/M phase arrest.
PMID- 26433664
TI - Correlation between microRNA-21 and expression of Th17 and Treg cells in
microenvironment of rats with hepatocellular carcinoma.
AB - OBJECTIVE: To study the correlation between miR-21 and Treg/Th17 ratio in the
microenvironment of rats with hepatocellular carcinoma. METHODS:
Diethylnitrosamine was used to build the hepatocellular carcinoma model of rats;
the content of Treg cells and Th17 cells and the expression of miR-21 in the
peripheral blood of rats with hepatocellular carcinoma were detected. The
statistical analysis was performed on the correlation between miR-21 expression
and Treg/Th17 ratio. RESULTS: Hepatocellular carcinoma model of rats was
successfully constructed. The proportion of Th17 cells among all CD4(+)T cells in
the peripheral blood of rats with hepatocellular carcinoma was 5.319%, which was
higher than the control group; while the proportion of Treg cells was 9.472%,
which was higher than the control group. Treg/Th17 ratio in the model group was
1.781, compared with 1.478 in the control group. The expression of miR-21 was
increased in the peripheral blood of rats with hepatocellular carcinoma and it
showed a positive correlation with the ratio of Treg/Th17. CONCLUSIONS: There is
a positive correlation between the expression level of miR-21 and the ratio of
Treg/Th17.
PMID- 26433665
TI - Effect of CXCR4 pretreated with ultrasound-exposed microbubbles on accelerating
homing of bone marrow mesenchymal stem cells to ischemic myocardium in AMI rats.
AB - OBJECTIVE: To investigate the role and potential mechanism of CXCR4 in promoting
targeted homing of bone marrow mesenchymal stem cells (BMSCs) with ultrasound
exposed microbubbles (UM) pretreatment. METHODS: Third generation BMSCs were
divided into four groups control group, ultrasound (US) group, UM group and
ultrasound-exposed microbubbles plus catalase group. RT-PCR and western blot were
performed to determine the levels of CXCR4 mRNA transcription and protein
expression, respectively. Third generation BMSCs were labeled with Fluo-alpha/AM
and divided into three groups: control group, US group and UM group, and
fluorescence intensities in the cells were observed immediately, 5 min and 15 min
after intervention under fluorescence microscope. The calcium iron levels in the
cells were analyzed. BMSCs were divided into five group: group A without calcium
in the medium, group B, group C, group D and group E containing calcium chloride
with concentration of l mol, 2 mol, 4 mol, anti-calcium-sensing receptor
antibody, respectively. RT-PCR and western blot were performed to determine the
levels of CXCR4 mRNA transcription and proteins expression of the third
generation BMSCs of each group, respectively. RESULTS: The levels of CXCR4 mRNA
transcription and protein expression between US group and control group had no
statistically significant difference (P > 0.05) shown by RT-PCR and western blot;
the transcription level in the UM group was significantly higher than that in US
group and control group (P < 0.05); and in the ultrasound-exposed microbubbles
plus catalase group, the transcription level was much lower than that in UM
group. Fluorescence intensify in the cells of US group had no significant
difference compared with that in the cells of the control group (P > 0.05), which
in the cells of UM group was significantly higher than that in the cells of both
US group and control group (P < 0.05). Compared to group A, expressions of CXCR4
of group B to D were significantly increased in concentration-dependent manner
showed by RT-PCR and western blot (P < 0.05). Compared to group C, expressions of
CXCR4 of group E were significantly decreased (P < 0.05). CONCLUSIONS: UM can
promote the influx of calcium in BMSCs and increase mRNA transcription and
protein expression of CXCR4. The latter may partly be caused by influx of
calcium.
PMID- 26433666
TI - Uterine sarcomas.
PMID- 26433667
TI - Cancer of the ovary, fallopian tube, and peritoneum.
PMID- 26433668
TI - Update on the diagnosis and management of gestational trophoblastic disease.
PMID- 26433669
TI - The future role of molecular staging in gynecologic cancer.
PMID- 26433670
TI - Pathology of cancers of the female genital tract.
PMID- 26433671
TI - Principles of chemotherapy.
PMID- 26433672
TI - Targeted therapy in gynecologic cancers: Ready for prime time?
PMID- 26433673
TI - Principles of radiation therapy in low-resource and well-developed settings, with
particular reference to cervical cancer.
PMID- 26433674
TI - Psychosexual health in gynecological cancer.
PMID- 26433675
TI - Rehabilitation after gynecological cancer treatment.
PMID- 26433676
TI - Palliative care in gynecological cancer.
PMID- 26433677
TI - FIGO Cancer Report 2015.
PMID- 26433678
TI - Cancer of the vulva.
PMID- 26433679
TI - Cancer of the vagina.
PMID- 26433680
TI - Cancer of the cervix uteri.
PMID- 26433681
TI - Cancer of the corpus uteri.
PMID- 26433682
TI - Aging causes morphological alterations in astrocytes and microglia in human
substantia nigra pars compacta.
AB - Age being a risk factor for Parkinson's disease, assessment of age-related
changes in the human substantia nigra may elucidate its pathogenesis. Increase in
Marinesco bodies, alpha-synuclein, free radicals and so forth in the aging nigral
neurons are clear indicators of neurodegeneration. Here, we report the glial
responses in aging human nigra. The glial numbers were determined on Nissl
stained sections. The expression of glial fibrillary acidic protein, S100beta,
2', 3'-cyclic nucleotide 3' phosphodiesterase, and Iba1 was assessed on
cryosections of autopsied midbrains by immunohistochemistry and densitometry. The
glial counts showed a biphasic increase, of which, the first prominent phase from
fetal age to birth could be physiological gliogenesis whereas the second one
after middle age may reflect mild age-related gliosis. Astrocytic morphology was
altered, but glial fibrillary acidic protein expression increased only mildly.
Presence of type-4 microglia suggests possibility of neuroinflammation. Mild
reduction in 2', 3'-cyclic nucleotide 3' phosphodiesterase-labeled area denotes
subtle demyelination. Stable age-related S100beta expression indicates absence of
calcium overload. Against the expected prominent gliosis, subtle age-related
morphological alterations in human nigral glia attribute them a participatory
role in aging.
PMID- 26433684
TI - The importance of influenza diagnosis.
PMID- 26433685
TI - Polio in Pakistan--A public health event of international concern with
implications for travellers' vaccination.
PMID- 26433686
TI - Early disruption of neurovascular units and microcirculatory dysfunction in the
spinal cord in spinal muscular atrophy type I.
AB - Spinal muscular atrophy type I (SMA-I) is characterized by progressive muscle
weakness with onset in early infancy, usually resulting in mortality before two
years of age. However, the processes underlying the pathophysiological
progression of the disease remain unclear. Prior to the onset of muscle weakness,
a regression of local capillaries is observed along with motor neuron loss. Local
populations of neurons, astrocytes, and vascular endothelial cells constitute a
neurovascular unit (NVU), in which neuronal and synaptic metabolism is tightly
coupled to capillary blood flow by astrocyte-mediated vasodilatory control. We
hypothesize that survival motor neuron protein deficiency and initial neuronal
dysfunction leads to the regression of vascular beds and the disruption of NVU
function. As a result, local capillary blood flow becomes insufficient, leading
to metabolic stress in neurons, endothelial cells, pericytes, and astrocytes,
ultimately disrupting the astrocytic regulation of capillaries. This pathogenic
process may accelerate the loss of anterior horn motor neurons, leading to the
further regression of capillaries and astroglial dysfunction. Hypocapnia,
resulting from dehydration and hyperventilation during therapeutic manual
ventilation, might further damage the NVU. Moreover, disruption of the
microcirculation may affect sympathetic and sensory neurons in the spinal cord,
contributing to sympathetic hyperactivity and sensory nerve degeneration,
respectively. These mutually reinforcing processes may underlie the progression
of muscle weakness during infancy in SMA-I. Therefore, disruption of the NVU and
a stressful neurovascular environment in the anterior horn may play important
roles in disease initiation and/or progression in SMA-I. The NVU is therefore a
critical therapeutic target for treating SMA-I. Our hypothetical model may
provide insight into why most neuroprotective strategies that do not address
astroglial and vascular cell dysfunction have limited efficacy.
PMID- 26433683
TI - The endoplasmic reticulum: structure, function and response to cellular
signaling.
AB - The endoplasmic reticulum (ER) is a large, dynamic structure that serves many
roles in the cell including calcium storage, protein synthesis and lipid
metabolism. The diverse functions of the ER are performed by distinct domains;
consisting of tubules, sheets and the nuclear envelope. Several proteins that
contribute to the overall architecture and dynamics of the ER have been
identified, but many questions remain as to how the ER changes shape in response
to cellular cues, cell type, cell cycle state and during development of the
organism. Here we discuss what is known about the dynamics of the ER, what
questions remain, and how coordinated responses add to the layers of regulation
in this dynamic organelle.
PMID- 26433687
TI - An evolutionary perspective on the immunomodulatory role of hydrogen sulphide.
AB - Most preclinical studies on endogenous hydrogen sulphide signalling have given
little consideration to the fact that the human body contains more bacterial
cells than human cells, and that evolution provides the context for all biology.
Whether hydrogen sulphide is pro or anti-inflammatory is heavily debated within
the literature, yet researchers have not fully considered that invasive bacteria
produce hydrogen sulphide, often at levels far above the endogenous levels of the
host. Here I argue that if hydrogen sulphide is an endogenous signalling molecule
with immunomodulatory functions, then it must have evolved in the presence of
virulent bacteria which produce hydrogen sulphide. This context leads to two
competing theories about the evolution of endogenous hydrogen sulphide
signalling. The detectable emission theory proposes that bacteria produce
hydrogen sulphide as part of normal metabolism and hosts which evolved to detect
and respond to this hydrogen sulphide would gain a selective survival advantage.
This predicts that the endogenous production of hydrogen sulphide is a mechanism
which amplifies the bacterial hydrogen sulphide signal. The opposing protective
agent theory predicts that bacterial hydrogen sulphide is an effective defence
against the bactericidal mechanisms of the host's immune response. In this case,
endogenous hydrogen sulphide production is either at inconsequential levels to
alter the immune response, or is involved in the inflammation resolution process.
Evidence suggests that the direct interactions of hydrogen sulphide with the
bactericidal mechanisms of the innate immune system are most congruent with the
protective agent theory. Therefore, I argue that if hydrogen sulphide is an
immunomodulatory endogenous signalling molecule its effects are most likely anti
inflammatory.
PMID- 26433688
TI - Does perineural invasion of the myenteric plexus have a key role in annular
rectal invasion and digestive system symptoms of prostate carcinoma patients?
AB - Prostate carcinoma is one of the most common cancers globally. It relatively
rarely invades the rectum, accounting for only about 4% of resected cases. About
half of these cases of rectal invasion show an annular rectal stricture pattern.
It has been hypothesized that anatomical structures, namely Denonvilliers fascia,
may play an important role in annular rectal involvement of prostate carcinoma.
Here, we propose another hypothesis: the reason for annular rectal invasion by
prostate carcinoma is its extension along the myenteric plexus (Auerbach's
plexus). We illustrate this using a case presentation and description of the
symptoms of such cases. From a review of the literature, autonomic digestive
system symptoms of rectal invasion of prostatic carcinoma, such as diarrhea,
tenesmus, or fecal incontinence is seen in about half of cases, coinciding with
the frequency of annular rectal invasion. Thus, by modifying the long-established
hypothesis, our suggestion that prostate carcinoma spreads along the myenteric
plexus when cancer cells invade beyond the Denonvilliers fascia to the rectum
could explain the cause and frequency not only of the annular rectal invasion but
also the digestive system symptoms related to this disease. The prognosis of
prostate carcinoma invading the rectum is very poor; however, this new hypothesis
might shed light on the digestive system symptoms associated with prostate
carcinoma and might lead to recognition and treatment of these cases at a
relatively early stage of rectal invasion.
PMID- 26433690
TI - Trends Form Follows Function: New Ways to Inform and Inspire.
PMID- 26433689
TI - Dietary diversity, meal frequency and associated factors among infant and young
children in Northwest Ethiopia: a cross- sectional study.
AB - BACKGROUND: Inappropriate feeding practice increases risk of under nutrition,
illness, and mortality amongst children less than 2 years of age. The objective
of this study is to assess minimum dietary diversity, meal frequency and its
associated factors among infant and young children aged 6-23 months in Dangila
Town, Northwest Ethiopia. METHODS: A community based cross sectional study was
conducted. Simple random sampling technique was used to select study
participants. Interviewer administered questionnaire were used. Bivariate and
multivariable logistic regression analyses was employed to identify factors
associated with minimum dietary diversity and meal frequency. RESULTS: A total of
920 children 6-23 months were included. Proportion of children who met the
minimum dietary diversity and meal frequency was 12.6 and 50.4 %, respectively.
Mothers education [AOR =2.52], age of a child [AOR = 2.05], birth order of index
child [AOR = 2.08], living in urban area [AOR = 2.09], having home gardening [AOR
= 2.03], and media exposure [AOR = 2.74] were positively associated with dietary
diversity. Moreover, age of the child [AOR = 3.03], birth order of index child
[AOR = 1.58], mothers involvement in decision making [AOR = 1.51], media exposure
[AOR = 2.62], and having postnatal visit [AOR = 2.30] were positively associated
with meal frequency. CONCLUSION: The proportion of children who received minimum
dietary diversity and meal frequency was low. Being at younger age, first birth
order, and lack of media exposure affect both dietary diversity and meal
frequency. Increasing mother's education, home gardening, mass media promotion
and empowering women in decision making are highly recommended to increase
dietary diversity and meal frequency.
PMID- 26433691
TI - Is There Sufficient Evidence to Consider Bacillus thuringiensis a Multihost
Pathogen? Response to Loguercio and Argolo-Filho.
PMID- 26433692
TI - The Tailocin Tale: Peeling off Phage Tails.
AB - Bacteria produce a variety of particles resembling phage tails that are
functional without an associated phage head. Acquired from diverse bacteriophage
sources, these stand-alone units were sculpted to serve different ecological
roles. Such tailocins mediate antagonism between related bacteria as well as
interactions with eukaryotic cells.
PMID- 26433693
TI - Rates of Lateral Gene Transfer in Prokaryotes: High but Why?
AB - Lateral gene transfer is of fundamental importance to the evolution of prokaryote
genomes and has important practical consequences, as evidenced by the rapid
dissemination of antibiotic resistance and virulence determinants. Relatively
little effort has so far been devoted to explicitly quantifying the rate at which
accessory genes are taken up and lost, but it is possible that the combined rate
of lateral gene transfer and gene loss is higher than that of point mutation.
What evolutionary forces underlie the rate of lateral gene transfer are not well
understood. We here use theory developed to explain the evolution of mutation
rates to address this question and explore its consequences for the study of
prokaryote evolution.
PMID- 26433695
TI - Sweet Talk: Protein Glycosylation in Bacterial Interaction With the Host.
AB - Pathogenic bacteria encode virulent glycosyltransferases that conjugate various
glycans onto substrate proteins via the N- or O-linkage. The HMW system in
nontypeable Haemophilus influenzae and the Pgl system in Campylobacter jejuni
glycosylate bacterial surface or periplasmic proteins at the eukaryotic-like Asn
X-Ser/Thr motif. The NleB effector from enterobacteria mediates arginine
GlcNAcylation of host death-domain proteins to block inflammation, representing
an atypical N-glycosylation. The large clostridial cytotoxins and related
glucosyltransferase toxins from Legionella and Photorhabdus monoglycosylate a
serine/threonine or tyrosine in host Rho GTPase or elongation factor 1A (eEF1A).
The emerging bacterial autotransporter heptosyltransferase (BAHT) family of
heptosyltransferases also catalyses O-glycosylation and modifies autotransporters
for adhesion to the host. These glycosylations, diverse in linkages and glycan
structures, determine appropriate functioning of bacterial virulence factors or
hijack host cellular processes in pathogenesis.
PMID- 26433694
TI - Roles of Lipoproteins and Apolipoproteins in Particle Formation of Hepatitis C
Virus.
AB - More than 160 million people worldwide are infected with hepatitis C virus (HCV),
and cirrhosis and hepatocellular carcinoma induced by HCV infection are life
threatening diseases. HCV takes advantage of many aspects of lipid metabolism for
an efficient propagation in hepatocytes. Due to the morphological and
physiological similarities of HCV particles to lipoproteins, lipid-associated HCV
particles are named lipoviroparticles. Recent analyses have revealed that
exchangeable apolipoproteins directly interact with the viral membrane to
generate infectious HCV particles. In this review, we summarize the roles of
lipid metabolism in the life cycle of HCV.
PMID- 26433696
TI - Natural Product Biosynthetic Diversity and Comparative Genomics of the
Cyanobacteria.
AB - Cyanobacteria are an ancient lineage of slow-growing photosynthetic bacteria and
a prolific source of natural products with intricate chemical structures and
potent biological activities. The bulk of these natural products are known from
just a handful of genera. Recent efforts have elucidated the mechanisms
underpinning the biosynthesis of a diverse array of natural products from
cyanobacteria. Many of the biosynthetic mechanisms are unique to cyanobacteria or
rarely described from other organisms. Advances in genome sequence technology
have precipitated a deluge of genome sequences for cyanobacteria. This makes it
possible to link known natural products to biosynthetic gene clusters but also
accelerates the discovery of new natural products through genome mining. These
studies demonstrate that cyanobacteria encode a huge variety of cryptic gene
clusters for the production of natural products, and the known chemical diversity
is likely to be just a fraction of the true biosynthetic capabilities of this
fascinating and ancient group of organisms.
PMID- 26433697
TI - Antiviral Monoclonal Antibodies: Can They Be More Than Simple Neutralizing
Agents?
AB - Monoclonal antibodies (mAbs) are increasingly being considered as agents to fight
severe viral diseases. So far, they have essentially been selected and used on
the basis of their virus-neutralizing activity and/or cell-killing activity to
blunt viral propagation via direct mechanisms. There is, however, accumulating
evidence that they can also induce long-lasting protective antiviral immunity by
recruiting the endogenous immune system of infected individuals during the period
of immunotherapy. Exploiting this property may revolutionize antiviral mAb-based
immunotherapies, with benefits for both patients and healthcare systems.
PMID- 26433698
TI - [The competence of the family physician in the care of patients at the end of
life. Reflections on the proposal of Specific Competence Area in Palliative
Care].
PMID- 26433699
TI - [Cost-efficacy of new antiviral treatments for chronic hepatitis C].
PMID- 26433701
TI - Reassuringly calm? Self-reported patterns of responses to reassurance seeking in
obsessive compulsive disorder.
AB - BACKGROUND AND OBJECTIVES: The perception of threat and associated feelings of
anxiety typically prompt people to seek safety; reassurance seeking is an
interpersonal strategy almost universally used to reduce the immediate perception
of risk. Excessive Reassurance Seeking (ERS) is considered to be particularly
prominent and unequivocally counter-productive in people suffering from anxiety
disorders in general and OCD in particular, producing short term relief but a
longer term return and worsening of the original anxiety. We evaluated the extent
and specificity of the effects of ERS in OCD and mechanisms involved in both
anxiety relief and the hypothesized later return of anxiety.. METHOD: Self rated
effects of reassurance seeking were investigated in 153 individuals with OCD, 50
with panic disorder, and 52 healthy controls, evaluating reactions to the
provision and non-provision of reassurance. RESULTS: Reassurance is associated
with short term relief then longer term return of both discomfort and the urge to
seek further reassurance in both anxious groups; healthy controls do not
experience significant resurgence. Greater return of anxiety and urge to seek
more reassurance were associated with higher levels of overall reassurance
seeking.. LIMITATIONS: The findings were based on retrospective self-report of
naturally occurring episodes of ERS; prospective studies and induced behaviours
are now needed. CONCLUSIONS: Not only is reassurance a quick fix for people
experiencing OCD, but in the absence of treatment the only fix! The findings
explain why reassurance seeking continues despite advice that it will worsen
anxiety problems. Such advice is potentially harmful to patients and their loved
ones..
PMID- 26433700
TI - The negativity bias predicts response rate to Behavioral Activation for
depression.
AB - BACKGROUND AND OBJECTIVES: This treatment study investigated the extent to which
asymmetric dimensions of affective responding, specifically the positivity offset
and the negativity bias, at pretreatment altered the rate of response to
Behavioral Activation treatment for depression. METHOD: Forty-one depressed
participants were enrolled into 16 weekly sessions of BA. An additional 36
lifetime healthy participants were evaluated prospectively for 16 weeks to
compare affective responding between healthy and remitted patients at post
treatment. All participants were assessed at Weeks 0, 8 and 16 using repeated
measures, involving a structured clinical interview for DSM-IV Axis I disorders,
questionnaires, and a computerized task designed to measure affective responses
to unpleasant, neutral, and pleasant images. RESULTS: The negativity bias at pre
treatment predicted the rate of response to BA, while the positivity offset did
not. LIMITATIONS: Only one treatment condition was used in this study and
untreated depressed participants were not enrolled, limiting our ability to
compare the effect of BA. CONCLUSIONS: Baseline negativity bias may serve as a
signal for patients to engage in and benefit from the goal-directed BA
strategies, thereby accelerating rate of response.
PMID- 26433702
TI - Simplified 2-tier histologic grading system accurately predicts outcomes in
goblet cell carcinoid of the appendix.
AB - Goblet cell carcinoid (GCC) is a rare appendiceal malignancy with both
neuroendocrine and glandular features. Clinical outcomes of patients with GCC
vary widely and a histology-based 3-tiered prognostic scheme has been previously
suggested; however, this scheme is subjective and challenging to apply in day-to
day practice. We sought to construct a simplified and prognostic grading system
based on objective histologic features with specific criteria. A continuous
population-based cohort of GCC with clinical outcome data and archival tissue
available for review was extracted from regional databases. For the 78 patients
with confirmed appendiceal GCC, specific histologic features, including cytologic
atypia, peritumoral stromal desmoplasia, and solid growth pattern, were recorded,
and a scoring system was devised, which separates patients with GCC into low
grade (n = 55; 71%) or high-grade (n = 23; 29%) histology. Correspondingly,
clinical follow-up data show good prognosis in those with low-grade histology
with median and 10-year overall survival of 51.0 months and 80.5%, respectively,
whereas those with high-grade histology have a poor prognosis with median and 10
year overall survival of 16.5 months (P = .006) and 0% (P < .001), respectively.
Multivariate Cox proportional hazard modeling demonstrates that this 2-tier
histologic system remains predictive of overall survival when controlled for TNM
clinicopathological stage. These data show that a simple and objective histologic
scoring system separates GCC into low- and high-grade histology with divergent
clinical outcomes.
PMID- 26433703
TI - FOXG1 expression shows correlation with neuronal differentiation in cerebellar
development, aggressive phenotype in medulloblastomas, and survival in a
xenograft model of medulloblastoma.
AB - FOXG1 is a transcription factor that interacts with multiple signaling pathways
and modulates neuronal differentiation in the telencephalon. Dysregulation of
FOXG1 expression has been previously reported in medulloblastoma. In this study,
we demonstrate a regional specific expression of FOXG1 and its colocalization
with Nestin expression in the premigratory mitotically active (outer) layer of
the external granular layer of the cerebellum. An inverse expression of the
granular precursor cell markers, Math1 and Musashi1, in the inner nonmitotic
migratory layer of the external granular layer and in the internal granular layer
was observed. Furthermore, modulation of FOXG1 in the medulloblastoma cell line,
DAOY, was associated with the induction of neuronal differentiation markers and
significant changes in multiple signaling pathways regulating cell proliferation,
differentiation, survival, and apoptosis. Additionally, we observed enhanced
survival in intracerebellar mice xenografts injected with DAOY cells bearing
shFOXG1 constructs versus shLuciferase construct. Overall, these findings suggest
that down-modulation of FOXG1 is a prerequisite for the onset of neuronal
differentiation during cerebellar development and that a decrease of FOXG1 in
medulloblastoma cells offers a survival advantage in mice. We propose that the
disruption of signaling pathways that promote mature neuronal differentiation by
overexpressed FOXG1 is a contributing event in the neoplastic transformation of
cerebellar stem cells.
PMID- 26433704
TI - IL-18 is highly expressed in inflammatory infiltrates of submandibular glands in
patients with immunoglobulin G4-related disease.
AB - Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a new disease entity
characterized by high serum IgG4 concentrations, infiltration of IgG4-positive
plasmacytes, and fibrosis of various organs. Several groups have reported that
IgG4-RD is a unique inflammatory disorder characterized by an immune reaction
predominantly mediated by T helper (Th) 2 and regulatory T cells. Meanwhile,
recent studies have demonstrated that interleukin (IL) 18 has a potential to
trigger the production of Th2 cytokines by Th1 cells. We analyzed IL-18
expression in submandibular glands of patients with IgG4-RD (20 cases) and
controls (19 cases) by immunohistochemical analysis and quantitative real-time
reverse-transcription polymerase chain reaction. We found that IL-18 was highly
expressed in submandibular glands of patients with IgG4-RD than in controls with
both protein (P < .05, chi(2) test) and messenger RNA levels (P < .05, Mann
Whitney U test). In addition, the expression of IL-18 and IL-13 was correlated in
submandibular glands of patients with IgG4-RD. Moreover, by analyzing dual
immunofluorescence staining, a few numbers of cells were double positive for IL
13 and interferon gamma at the inflammatory infiltrates of submandibular glands
of patients with IgG4-RD. These data suggest a possibility that IL-13 is produced
by Th1 cells. We speculated that IL-18 stimulates Th1 cells producing Th2
cytokines and enhances the immune reaction of Th2 cytokines in pathogenesis of
IgG4-RD.
PMID- 26433705
TI - An empirical model that uses light attenuation and plant nitrogen status to
predict within-canopy nitrogen distribution and upscale photosynthesis from leaf
to whole canopy.
AB - Modelling the spatial and temporal distribution of leaf nitrogen (N) is central
to specify photosynthetic parameters and simulate canopy photosynthesis. Leaf
photosynthetic parameters depend on both local light availability and whole-plant
N status. The interaction between these two levels of integration has generally
been modelled by assuming optimal canopy functioning, which is not supported by
experiments. During this study, we examined how a set of empirical relationships
with measurable parameters could be used instead to predict photosynthesis at the
leaf and whole-canopy levels. The distribution of leaf N per unit area (Na)
within the canopy was related to leaf light irradiance and to the nitrogen
nutrition index (NNI), a whole-plant variable accounting for plant N status. Na
was then used to determine the photosynthetic parameters of a leaf gas exchange
model. The model was assessed on alfalfa canopies under contrasting N nutrition
and with N2-fixing and non-fixing plants. Three experiments were carried out to
parameterize the relationships between Na, leaf irradiance, NNI and
photosynthetic parameters. An additional independent data set was used for model
evaluation. The N distribution model showed that it was able to predict leaf N on
the set of leaves tested. The Na at the top of the canopy appeared to be related
linearly to the NNI, whereas the coefficient accounting for N allocation remained
constant. Photosynthetic parameters were related linearly to Na irrespective of N
nutrition and the N acquisition mode. Daily patterns of gas exchange were
simulated accurately at the leaf scale. When integrated at the whole-canopy
scale, the model predicted that raising N availability above an NNI of 1 did not
result in increased net photosynthesis. Overall, the model proposed offered a
solution for a dynamic coupling of leaf photosynthesis and canopy N distribution
without requiring any optimal functioning hypothesis.
PMID- 26433706
TI - Growth habit and leaf economics determine gas exchange responses to high
elevation in an evergreen tree, a deciduous shrub and a herbaceous annual.
AB - Plant growth at high elevations necessitates physiological and morphological
plasticity to enable photosynthesis (A) under conditions of reduced temperature,
increased radiation and the lower partial pressure of atmospheric gases, in
particular carbon dioxide (pCO2). Previous studies have observed a wide range of
responses to elevation in plant species depending on their adaptation to
temperature, elevational range and growth habit. Here, we investigated the effect
of an increase in elevation from 2500 to 3500 m above sea level (a.s.l.) on three
montane species with contrasting growth habits and leaf economic strategies.
While all of the species showed identical increases in foliar delta(13)C, dark
respiration and nitrogen concentration with elevation, contrasting leaf gas
exchange and photosynthetic responses were observed between species with
different leaf economic strategies. The deciduous shrub Salix atopantha and
annual herb Rumex dentatus exhibited increased stomatal (Gs) and mesophyll (Gm)
conductance and enhanced photosynthetic capacity at the higher elevation.
However, evergreen Quercus spinosa displayed reduced conductance to CO2 that
coincided with lower levels of photosynthetic carbon fixation at 3500 m a.s.l.
The lower Gs and Gm values of evergreen species at higher elevations currently
constrains their rates of A. Future rises in the atmospheric concentration of CO2
([CO2]) will likely predominantly affect evergreen species with lower specific
leaf areas (SLAs) and levels of Gm rather than deciduous species with higher SLA
and Gm values. We argue that climate change may affect plant species that compose
high-elevation ecosystems differently depending on phenotypic plasticity and
adaptive traits affecting leaf economics, as rising [CO2] is likely to benefit
evergreen species with thick sclerophyllous leaves.
PMID- 26433707
TI - Genetic structure of coexisting wild and managed agave populations: implications
for the evolution of plants under domestication.
AB - Domestication is a continuous evolutionary process guided by humans. This process
leads to divergence in characteristics such as behaviour, morphology or genetics,
between wild and managed populations. Agaves have been important resources for
Mesoamerican peoples since prehistory. Some species are domesticated and others
vary in degree of domestication. Agave inaequidens Koch is used in central Mexico
to produce mescal, and a management gradient from gathered wild and silvicultural
populations, as well as cultivated plantations, has been documented. Significant
morphological differences were reported among wild and managed populations, and a
high phenotypic variation in cultivated populations composed of plants from
different populations. We evaluated levels of genetic diversity and structure
associated with management, hypothesizing that high morphological variation would
be accompanied by high genetic diversity in populations with high gene flow and
low genetic structure among managed and unmanaged populations. Wild,
silvicultural and cultivated populations were studied, collecting tissue of 19-30
plants per population. Through 10 nuclear microsatellite loci, we compared
population genetic parameters. We analysed partition of variation associated with
management categories to estimate gene flow among populations. Agave inaequidens
exhibits high levels of genetic diversity (He = 0.707) and moderate genetic
structure (FST = 0.112). No differences were found in levels of genetic diversity
among wild (He = 0.704), silviculturally managed (He = 0.733) and cultivated (He
= 0.698) populations. Bayesian analysis indicated that five genetic clusters best
fit the data, with genetic groups corresponding to habitats where populations
grow rather than to management. Migration rates ranged from zero between two
populations to markedly high among others (M = 0.73-35.25). Natural mechanisms of
gene flow and the dynamic management of agave propagules among populations favour
gene flow and the maintenance of high levels of variation within all populations.
The slight differentiation associated with management indicates that
domestication is in an incipient stage.
PMID- 26433708
TI - Temperature monitoring during microwave ablation in ex vivo porcine livers.
AB - OBJECTIVE: The aim of the present study was to assess the temperature map and its
reproducibility while applying two different MWA systems (915 MHz vs 2.45 GHz) in
ex vivo porcine livers. MATERIALS AND METHODS: Fifteen fresh pig livers were
treated using the two antennae at three different settings: treatment time of 10
min and power of 45 W for both systems; 4 min and 100 W for the 2.45 GHz system.
Trends of temperature were recorded during all procedures by means of fiber optic
based probes located at five fixed distances from the antenna, ranging between 10
mm and 30 mm. Each trial was repeated twice to assess the reproducibility of
temperature distribution. RESULTS: Temperature as function of distance from the
antenna can be modeled by a decreasing exponential trend. At the same settings,
temperature obtained with the 2.45 GHz system was higher than that obtained with
the 915 MHz thus resulting into a wider area of ablation (diameter 17 mm vs 15
mm). Both systems showed good reproducibility in terms of temperature
distribution (root mean squared difference for both systems ranged between 2.8
degrees C and 3.4 degrees C). CONCLUSIONS: When both MWA systems are applied, a
decreasing exponential model can predict the temperature map. The 2.45 GHz
antenna causes higher temperatures as compared to the 915 MHz thus, resulting
into larger areas of ablation. Both systems showed good reproducibility although
better results were achieved with the 2.45 GHz antenna.
PMID- 26433709
TI - Robotic blue-dye sentinel lymph node detection for endometrial cancer - Factors
predicting successful mapping.
AB - OBJECTIVE: Sentinel lymph node (SLN) mapping has emerged as a viable option for
the treatment of patients with endometrial cancer. We report our initial
experience with SLN mapping algorithm, and examine the factors predicting
successful SLN mapping. METHODS: We analyzed all data recorded in our institute
on robotic blue-dye SLN detection mapping from the time it was first introduced
to our department in January 2012-December 2014. Data included patient
demographics, SLN allocation, operating room times, and pathology results.
RESULTS: During the study period, 74 patients had robotic assisted surgery for
endometrial cancer with attempted SLN mapping. SLN was found overall in 46
patients (62.1%). At first, SLN was detected in only 50% of cases, but after
performing 30 cases, detection rates rose to 84.6% (OR = 3.34, CI 1.28-8.71; p =
0.003). Univariate analysis showed a higher detection rate with methylene blue
than patent blue dye, 74.3% vs. 52.3% (OR = 2.744, 95% CI 1.026-7.344; p =
0.042). In multivariate analysis, high body mass index (BMI) was associated with
failed mapping (OR = 0.899; 95% CI 0.808-1.00), as was the presence of lymph
vascular space invasion (LVSI) (OR = 0.126; 95% CI 0.24-0.658) and few cases per
surgeon (OR = 1.083, 95% CI 1.032-1.118). Factors related to uterine pathology
itself, including tumor histology, grade, method of diagnosis, the presence of an
endometrial polyp, and lower uterine segment involvement were not found to be
associated with successful mapping. CONCLUSIONS: Surgeon experience, BMI and LVSI
may affect the success rate of SLN mapping for endometrial cancer. These factors
should be investigated further in future studies.
PMID- 26433711
TI - Efficiency of an education program on the safety knowledge and skills of patients
with rheumatoid arthritis treated by biologics.
PMID- 26433712
TI - And the history goes on.
PMID- 26433710
TI - Anti-pseudo-PCNA type 1 (anti-SG2NA) pattern: Track down Cancer, not SLE.
AB - OBJECTIVE: Describe the clinical significance of anti-SG2NA antibodies also
called anti-pseudo-PCNA type 1 (proliferating cell nuclear antigen auto
antibodies) which are rare antinuclear antibodies (ANAs) staining distinctly S/G2
proliferative HEp-2 cells by indirect immunofluorescence. By analogy with anti
PCNA antibodies, they have been suspected to be associated with systemic lupus
erythematosus (SLE), cancers or viral diseases. METHODS: From May 2006 to
February 2013, 16,827 patients were tested positive for ANAs in the Laboratory of
Immunology, Strasbourg, France. We retrospectively analyzed clinical and
biological data from 126 patients with anti-pseudo-PCNA type 1 antibodies.
RESULTS: There was a 0.75% prevalence of anti-pseudo-PCNA type 1 Abs among
ANAs(+) patients. Median age was 56.9 years (standard deviation [SD] 13.4 years)
with a sex ratio female/male of 1.9. Compared to ANAs(+) patients, many more
patients have been hospitalized in the Oncology and Hematology Department (23%
vs. 6.3%, P < 0.05). Indeed, anti-pseudo-PCNA type 1 Abs were detected in 33
patients suffering from solid and hematological cancers (26%). Another group of
patients presented various auto-immune diseases but surprisingly none of our
patients was affected with SLE when 5 out of 8 patients in anti-PCNAs(+) Abs
group (P < 5.10(-6)) were. Finally, the presence of anti-pseudo-PCNA type 1 Abs
was associated in 30 cases with other auto-Abs reflecting a more general
breakdown of B cell tolerance against other self-antigens. CONCLUSION:
Considering our results, explorations for tumors should be at least recommended
for patients with anti-pseudo-PCNA type 1 Abs. Lupus disease is not associated
with these autoAbs.
PMID- 26433713
TI - Evaluation and treatment of Sjogren's syndrome in focus.
PMID- 26433714
TI - Characterization of alkaline phosphatase activity in seminal plasma and in fresh
and frozen-thawed stallion spermatozoa.
AB - Alkaline phosphatase (AP) has been studied in several situations to elucidate its
role in reproductive biology of the male from different mammalian species; at
present, its role in horse sperm physiology is not clear. The aim of the present
work was to measure AP activity in seminal plasma and sperm extracts from freshly
ejaculated as well as in frozen-thawed stallion spermatozoa and to verify whether
relationship exists between AP activity and sperm quality parameters. Our data on
40 freshly ejaculated samples from 10 different stallions demonstrate that the
main source of AP activity is seminal plasma, whereas sperm extracts contribution
is very low. In addition, we found that AP activity at physiological pH (7.0) is
significantly lower than that observed at pH 8.0, including the optimal AP pH (pH
10.0). Alkaline phosphatase did not exert any effect on sperm-oocyte interaction
assessed by heterologous oocyte binding assay. Additionally, we observed a
thermal stability of seminal plasma AP, concluding that it is similar to that of
bone isoforms. Positive correlations were found between seminal plasma AP
activity and sperm concentration, whereas a negative correlation was present
between both spermatozoa extracts and seminal plasma AP activity and seminal
plasma protein content. A significant decrease in sperm extract AP activity was
found in frozen-thawed samples compared with freshly ejaculated ones (n = 21),
concomitantly with the decrease in sperm quality parameters. The positive
correlation between seminal plasma AP activity measured at pH 10 and viability of
frozen-thawed spermatozoa suggests that seminal plasma AP activity could be used
as an additional predictive parameter for stallion sperm freezability. In
conclusion, we provide some insights into AP activity in both seminal plasma and
sperm extracts and describe a decrease in AP after freezing and thawing.
PMID- 26433715
TI - Verbal memory and menopause.
AB - Midlife women frequently report memory problems during the menopausal transition.
Recent studies validate those complaints by showing significant correlations
between memory complaints and performance on validated memory tasks. Longitudinal
studies demonstrate modest declines in verbal memory during the menopausal
transition and a likely rebound during the postmenopausal stage. Clinical studies
that examine changes in memory following hormonal withdrawal and add-back hormone
therapy (HT) demonstrate that estradiol plays a critical role in memory. Although
memory changes are frequently attributed to menopausal symptoms, studies show
that the memory problems occur during the transition even after controlling for
menopausal symptoms. It is well established that self-reported vasomotor symptoms
(VMS) are unrelated to objective memory performance. However, emerging evidence
suggests that objectively measured VMS significantly correlate with memory
performance, brain activity during rest, and white matter hyperintensities. This
evidence raises important questions about whether VMS and VMS treatments might
affect memory during the menopausal transition. Unfortunately, there are no
clinical trials to inform our understanding of how HT affects both memory and
objectively measured VMS in women in whom HT is indicated for treatment of
moderate to severe VMS. In clinical practice, it is helpful to normalize memory
complaints, to note that evidence suggests that memory problems are temporary,
and to counsel women with significant VMS that memory might improve with
treatment.
PMID- 26433716
TI - Wegener granulomatosis with supraglottic involvement.
PMID- 26433717
TI - Effect of a mouthrinse containing rice peptide CL(14-25) on early dental plaque
regrowth: a randomized crossover pilot study.
AB - BACKGROUND: We aimed to evaluate clinically the effect of mouthrinse containing a
rice peptide on early dental plaque regrowth. METHODS: The study was designed as
a double-masked, two-group crossover randomized pilot trial, involving 10
periodontally healthy volunteers. After receiving a professional tooth cleaning
at baseline, over the next 3 days each participant refrained from all oral
hygiene measures and had two daily rinses with 20 ml of the test mouthrinse
containing 0.4 % rice peptide CL(14-25) or placebo rinse. At the end of each
experimental period, plaque score was assessed using the modified Volpe's method,
and the participants filled out a questionnaire. Each participant underwent a 7
day washout period followed by a second allocation. The plaque score was the
primary outcome of the study and participant perception was the secondary
outcome. RESULTS: No adverse effects were observed in the participants during the
study. Clinically, the mean plaque score of the examined teeth was significantly
lower in the test group (2.44 +/- 0.74, CI: 1.91-2.96) than the placebo group
(2.65 +/- 0.63, CI: 2.20-3.10) (P < 0.05). When analyzed according to the type of
teeth, a significantly lower score of the premolars/molars was observed in the
test group (2.39 +/- 0.68, CI: 2.08-2.71) than that in the placebo group (2.66 +/
0.58, CI: 2.39-2.93) (P < 0.05). CONCLUSIONS: The mouthrinse containing 0.4 %
rice peptide CL(14-25) was effective in reducing the early regrowth of dental
plaque. However, clinical relevance of this efficacy needs to be validated in a
future large-scale study. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN
CTR) R000014000. Date of formal registration: November 1, 2013.
PMID- 26433719
TI - Decreased Antibiotic Consumption in the Belgian Community: Is It Credible?
PMID- 26433718
TI - Supply-side dimensions and dynamics of integrating HIV testing and counselling
into routine antenatal care: a facility assessment from Morogoro Region,
Tanzania.
AB - BACKGROUND: Integration of HIV into RMNCH (reproductive, maternal, newborn and
child health) services is an important process addressing the disproportionate
burden of HIV among mothers and children in sub-Saharan Africa. We assess the
structural inputs and processes of care that support HIV testing and counselling
in routine antenatal care to understand supply-side dynamics critical to scaling
up further integration of HIV into RMNCH services prior to recent changes in HIV
policy in Tanzania. METHODS: This study, as a part of a maternal and newborn
health program evaluation in Morogoro Region, Tanzania, drew from an assessment
of health centers with 18 facility checklists, 65 quantitative and 57 qualitative
provider interviews, and 203 antenatal care observations. Descriptive analyses
were performed with quantitative data using Stata 12.0, and qualitative data were
analyzed thematically with data managed by Atlas.ti. RESULTS: Limitations in
structural inputs, such as infrastructure, supplies, and staffing, constrain the
potential for integration of HIV testing and counselling into routine antenatal
care services. While assessment of infrastructure, including waiting areas,
appeared adequate, long queues and small rooms made private and confidential HIV
testing and counselling difficult for individual women. Unreliable stocks of HIV
test kits, essential medicines, and infection prevention equipment also had
implications for provider-patient relationships, with reported decreases in
women's care seeking at health centers. In addition, low staffing levels were
reported to increase workloads and lower motivation for health workers. Despite
adequate knowledge of counselling messages, antenatal counselling sessions were
brief with incomplete messages conveyed to pregnant women. In addition, coping
mechanisms, such as scheduling of clinical activities on different days, limited
service availability. CONCLUSION: Antenatal care is a strategic entry point for
the delivery of critical tests and counselling messages and the framing of
patient-provider relations, which together underpin care seeking for the
remaining continuum of care. Supply-side deficiencies in structural inputs and
processes of delivering HIV testing and counselling during antenatal care
indicate critical shortcomings in the quality of care provided. These must be
addressed if integrating HIV testing and counselling into antenatal care is to
result in improved maternal and newborn health outcomes.
PMID- 26433720
TI - Epidemiology of Hepatitis B and Hepatitis C Infections and Benefits of Programs
for Hepatitis Prevention in Northeastern China: A Cross-Sectional Study.
AB - BACKGROUND: To investigate the epidemiology of hepatitis B and C infections and
the benefits of programs aimed at hepatitis prevention and control in
Northeastern China. METHODS: Individuals receiving health examinations were
recruited to complete a questionnaire and undergo laboratory tests for hepatitis
infection. Data on demographic characteristics, results of hepatitis B virus
(HBV) and hepatitis C virus (HCV) serological tests, for HBV and HCV infection
were analyzed. RESULTS: Among 227 808 study participants, the hepatitis B surface
antigen (HBsAg) and anti-HCV-positive rates were 6.1% and 3.0%, respectively.
Among HBsAg-positive participants, 63.8% tested positive for HBV DNA, 20.2% had
an abnormal alanine aminotransferase (ALT) level, and 10.7% had cirrhosis. Among
anti-HCV-positive participants, 57.2% tested positive for HCV RNA, 29.6% had an
abnormal ALT level, and 8.4% had cirrhosis. Among HBsAg- or anti-HCV-positive
participants, 47.1% and 32.0%, respectively, were aware of their infection. Among
participants infected with HBV or HCV and suitable for antivirus treatment, 23.5%
and 16.1%, respectively, had received antivirus treatment. The HBV plus HCV
coinfection rate was 0.08%. CONCLUSIONS: The HBsAg-positive rate decreased
significantly after implementation of recently introduced HBV control programs in
China. However, the anti-HCV-positive rate showed only a slight decrease,
indicating that programs for the prevention and control of hepatitis viruses
require continued strengthening. CHINESE CLINICAL TRIALS REGISTRATION: ChiCTR-ECS
13004009.
PMID- 26433721
TI - Swept source optical coherence tomography of a vitreal pocket entrapped in
myelinated retinal nerve fibers.
PMID- 26433723
TI - Effect of supplementation of beef cattle with different protein levels and
degradation rates during transition from the dry to rainy season.
AB - The objective of this study was to evaluate the effect of increasing the supply
of protein with different degradation rates on the performance and metabolism of
growing Nellore cattle reared on Brachiaria brizantha cv. Marandu pasture during
the transition period from the dry to rainy season. The experiment was installed
on an area of 34 ha, divided into 12 paddocks with an average area of 2.85 ha. In
the performance evaluation were utilized 72 recently weaned, non-castrated
Nellore cattle with an initial body weight (BW) of 199 kg (SEM = 16). The
following supplements were used: energy protein supplement containing 25% crude
protein (CP) (C-25) and energy protein supplements containing 40% CP with one
third highly degradable CP and two thirds poorly degradable CP (40-1/3NPN), one
half highly degradable CP and one half poorly degradable CP (40-1/2NPN), and two
thirds highly degradable CP and one third poorly degradable CP (40-2/3NPN).
Higher protein degradation rates reduced supplement intake (P < 0.01). In the
first period, animals consuming supplement 40-1/3NPN exhibited higher average
daily gain (ADG) (0.30 kg/day), similar to that of animals receiving supplement
40-1/2NPN (P = 0.04). In the second period, supplement 40-2/3NPN resulted in
lower ADG (0.19 kg/day less than the other supplements). There was no effect of
supplement on animal performance in the third period (P > 0.10), when ADG was
0.56 kg/day. In conclusion, the response to supplementation is associated with
interactions with characteristics of the forage canopy. Supplementation with a
true protein source will be beneficial only during the early stage of the dry
rainy season transition period.
PMID- 26433724
TI - Cross-Sectional Survey on Newborn Screening in Wisconsin Amish and Mennonite
Communities.
AB - Old Order Amish and Mennonites, or Plain populations, are a growing minority in
North America with unique health care delivery and access challenges coupled with
higher frequencies of genetic disorders. The objective of this study was to
determine newborn screening use and attitudes from western Wisconsin Plain
communities. A cross-sectional survey, with an overall response rate of 25 %,
provided data representing 2010 children. In households with children (n = 297),
the rate of newborn screening was 74 % and all children were screened in 40 % of
these households. Lack of access to testing was the most common reason for not
screening all children and parental age was inversely associated with testing.
The majority of respondents reported some or more knowledge of screening, viewed
screening as important, and had access to screening in their communities.
Households with children who had never received newborn screening (26 %) reported
lower frequencies of favorable responses in all categories compared to households
that had at least one child screened. The difference in access to newborn
screening was less marked between the groups compared to differences on knowledge
and consideration of its importance. Moreover, 55 % of households who had never
screened any of their children reported being unlikely or unsure of screening any
future children. A focus on improving access to newborn screening alongside
establishing approaches to change parental perceptions on the importance of
newborn screening is necessary for increasing newborn screening in these Plain
communities.
PMID- 26433722
TI - Transcriptional regulators of GntR family in Streptomyces coelicolor A3(2):
analysis in silico and in vivo of YtrA subfamily.
AB - Transcriptional factors of the GntR family regulate numerous physiological and
morphological processes in response to the nutrient state of bacterial cells. The
number of GntR transcriptional factors in genomes of soil-dwelling actinomycetes
is one of the highest among bacteria, reflecting both the large size of their
chromosomes and the complex ecological niche that they occupy. However, very
little is known about the roles of GntRs in actinomycete biology. Here, we
analyzed the genome of model actinomycete, Streptomyces coelicolor A3(2), in an
attempt to gain new insights into the function of GntR family. All 56 GntR
proteins of M145 strain were classified into FadR, HutC, MocR, YtrA, and DevA
subfamilies according to their secondary structure. We then checked for the
presence of GntR orthologs in six other sequenced Streptomyces and one
Kitasatospora genomes, revealing that 12 GntRs were conserved in all analyzed
strains. Genomic analysis of the less studied YtrA type regulators revealed 160
sequences present in 88 members of Coriobacteridae, Rubrobacteridae, and
Actinobacteridae subclasses. These proteins form seven dense clusters on the
consensus phylogenetic tree and their genes are usually co-located with the genes
for transport proteins. Probable operator sites were identified for orthologous
groups of Sco0823 and Sco3812 proteins. All S. coelicolor YtrA-like regulatory
genes (SCO0823, SCO1728, SCO3812) were analyzed at transcriptional level, knocked
out, and introduced on moderate copy number plasmid in M145 strain. Also, gene
SCO0824, a part of putative SCO0823 operon, was studied. Results of these
experiments are discussed here.
PMID- 26433725
TI - Community Stakeholders' Perceptions of Major Factors Influencing Childhood
Obesity, the Feasibility of Programs Addressing Childhood Obesity, and Persisting
Gaps.
AB - Prior research has identified numerous factors contributing to increased rates of
childhood obesity. However, few studies have focused explicitly on the experience
of community stakeholders in low-income communities. This study sought to capture
the perspectives of these on-the-ground experts regarding major factors
contributing to childhood obesity as well as gaps in current prevention and
control efforts. We conducted semi-structured interviews with 39 stakeholders
from different community sectors (e.g., healthcare providers, childcare
providers, teachers). Data were drawn from the Massachusetts Childhood Obesity
Research Demonstration project, a multi-level, multi-sector intervention designed
to reduce childhood obesity being implemented in two low-income communities in
Massachusetts. Interviews were conducted at baseline, transcribed, coded using
grounded theory approach, and analyzed in NVivo 10.0. The vast majority of
stakeholders had recently participated in obesity prevention strategies, and
nearly all of them identified gaps in prevention efforts either within their
organizations or in the broader community. In addition to factors previously
identified in the literature, several themes emerged including the need to change
policies to increase physical activity during school, offer healthier snacks in
schools and afterschool programs, and increase communication and collaboration
within the community in prevention efforts. Community stakeholders can impact the
success of interventions by bridging the gap between science and lived
experience. The results of this study can guide future research by highlighting
the importance of including stakeholders' frontline experiences with target
populations, and using information on identified gaps to augment intervention
planning efforts.
PMID- 26433726
TI - Current status of nontuberculous mycobacterial surgery in Japan: analysis of data
from the annual survey by the Japanese Association for Thoracic Surgery.
AB - OBJECTIVE: The prevalence of pulmonary disease caused by nontuberculous
mycobacteria (NTM) has been increasing in Japan. Adjuvant resectional surgery is
often recommended to lessen disease progression when the response to drug therapy
is poor. In all likelihood, as affected cases of NTM disease increase, so will
the number of operations. The goal of this study was to determine the current
status of NTM surgery in Japan by analyzing data from the annual survey of the
Japanese Association for Thoracic Surgery (JATS). METHODS: Data were obtained
from annual surveys conducted between 2008 and 2012. The annual number of
operations for pulmonary NTM disease was tabulated nationwide and in each region
(Hokkaido, Tohoku, Kanto, Tokyo, Chubu, Kinki, Chugoku/Shikoku, and Kyushu). For
comparison, the numbers for pulmonary tuberculosis and tuberculoma operations
were also obtained. RESULTS: The annual number of operations for pulmonary NTM
disease nationwide increased each year between 2008 and 2012: 292 (2008), 323
(2009), 452 (2010), 440 (2011), and 514 (2012); an overall increase of 76%.
Conversely, the annual numbers of operations for pulmonary tuberculosis were
stable: 145 (2008), 181 (2009), 117 (2010), 113 (2011), and 107 (2012), as were
the annual numbers of operations for tuberculoma: 386 (2008), 341 (2009), 320
(2010), 390 (2011), and 351 (2012). CONCLUSION: Data from the JATS annual survey
demonstrate a steady increase in the number of NTM surgeries in Japan. General
thoracic surgeons will continue to increasingly encounter NTM patients who are
candidates for surgery until a magic bullet against NTM disease is available.
PMID- 26433727
TI - Rapid Clozapine Titration in Patients with Treatment Refractory Schizophrenia.
AB - The aim of this study is to evaluate the safety and effectiveness of rapid
clozapine titration in patients with schizophrenia in hospital settings. We
conducted a retrospective two-center cohort study to compare the safety and
effectiveness of clozapine with different titration rates in treatment-refractory
patients with schizophrenia. In the first center, clozapine was started at 25-50
mg followed by 50-100 mg as needed every 6 h on day 1, followed by increases of
50-100 mg/day. In the second center, titration was slower; clozapine initiated
with 12.5-50 mg on day 1 followed by increases of 25-50 mg/day. The number of
days between starting of clozapine until discharge was shorter in the rapid
titration group (22.4 +/- 8.72 vs 27.0 +/- 10.5, p = 0.1). Number of days of
total hospital stay were significantly shorter in the rapid titration group (29.6
+/- 10.6 vs 41.2 +/- 14.8, p = 0.002). Hypotension was more common in the rapid
titration group and one patient had suspected myocarditis. Rapid clozapine
titration appeared safe and effective. The length of stay following initiation of
clozapine was shorter in the rapid-titration group, although this was not
statistically significant. However starting clozapine earlier together with rapid
titration has significantly shortened the length of hospital stay in patients
with treatment refractory schizophrenia.
PMID- 26433728
TI - Prognoses and treatment strategies for synchronous peritoneal dissemination of
colorectal carcinoma.
AB - PURPOSE: We devised a simple dichotomous classification system and showed
sufficient reproducibility to indicate treatment strategies for peritoneal
metastasis of colorectal cancer. METHODS: We included 67 patients with peritoneal
metastasis of colorectal cancer and classified them according to the largest
lesion size, number of lesions and number of regional peritoneal metastases. The
oncological data were recorded and compared. RESULTS: According to the univariate
analyses, the prognoses were significantly better in patients with <=3
disseminated lesions than in those with >=4, and in patients with disseminated
lesions in only one region than in those with >=2 lesions. A multivariate
analysis showed that primary tumor resection and the presence of peritoneal
metastases in only one region were favorable factors for the patient survival.
Patients with disseminated lesions in only one region (localized group) and those
with nonlocalized lesions had three-year survival rates of 45.6 and 12.2 %,
respectively. Finally, primary tumor resection improved the prognoses in both the
localized and nonlocalized groups. CONCLUSIONS: Colorectal cancer patients were
categorized into localized and nonlocalized groups according to the number of
regions with peritoneal metastasis, and significant prognostic associations were
demonstrated. Subsequent analyses of the oncological data suggested that primary
tumor resection contributes to an improved prognosis in all patients with
synchronous peritoneal metastases.
PMID- 26433729
TI - Exploiting the ubiquitin and phosphoinositide pathways by the Legionella
pneumophila effector, SidC.
AB - Intracellular bacterial pathogens use secreted effector proteins to alter host
cellular processes, with the goal of subverting host defenses and allowing the
infection to progress. One such pathogen, Legionella pneumophila, secretes ~300
proteins into its host to alter a number of pathways including intracellular
trafficking, phosphoinositide metabolism, and cell signaling. The Legionella
effector SidC was previously found to bind to PI(4)P and was responsible for the
enrichment of ER proteins and ubiquitinated species on the Legionella-containing
vacuoles. Through our recent work, we have discovered that SidC contains a unique
N-terminal E3 ubiquitin ligase domain and a C-terminal novel PI(4)P-binding
domain. Our results demonstrate that SidC serves to link two distinct cellular
pathways, ubiquitin and phosphoinositide. However, how the ubiquitin ligase
activity regulates host membrane trafficking events remains to be investigated.
PMID- 26433730
TI - An experimental study on the effects of a simulation game on students' clinical
cognitive skills and motivation.
AB - Simulation games are becoming increasingly popular in education, but more insight
in their critical design features is needed. This study investigated the effects
of fidelity of open patient cases in adjunct to an instructional e-module on
students' cognitive skills and motivation. We set up a three-group randomized
post-test-only design: a control group working on an e-module; a cases group,
combining the e-module with low-fidelity text-based patient cases, and a game
group, combining the e-module with a high-fidelity simulation game with the same
cases. Participants completed questionnaires on cognitive load and motivation.
After a 4-week study period, blinded assessors rated students' cognitive
emergency care skills in two mannequin-based scenarios. In total 61 students
participated and were assessed; 16 control group students, 20 cases students and
25 game students. Learning time was 2 h longer for the cases and game groups than
for the control group. Acquired cognitive skills did not differ between groups.
The game group experienced higher intrinsic and germane cognitive load than the
cases group (p = 0.03 and 0.01) and felt more engaged (p < 0.001). Students did
not profit from working on open cases (in adjunct to an e-module), which
nonetheless challenged them to study longer. The e-module appeared to be very
effective, while the high-fidelity game, although engaging, probably distracted
students and impeded learning. Medical educators designing motivating and
effective skills training for novices should align case complexity and fidelity
with students' proficiency level. The relation between case-fidelity, motivation
and skills development is an important field for further study.
PMID- 26433731
TI - Wilderness Medical Society Practice Guidelines for the Treatment of Pitviper
Envenomations in the United States and Canada.
PMID- 26433732
TI - Intrathecal Administration of Tempol Reduces Chronic Constriction Injury-Induced
Neuropathic Pain in Rats by Increasing SOD Activity and Inhibiting NGF
Expression.
AB - We investigate the antinociceptive effect of intrathecal and intraperitoneal
tempol administration in a rat model of chronic constriction injury (CCI)-induced
neuropathic pain and explore the underlying antinociceptive mechanisms of tempol.
Rats were randomly assigned to four groups (n = 8 per group): sham group, CCI
group, Tem1 group (intrathecal injection of tempol), and Tem2 group
(intraperitoneal injection of tempol). Neuropathic pain was induced by CCI of the
sciatic nerve. Tempol was intrathecally or intraperitoneally administered daily
for 7 days beginning on postoperative day one. The mechanical withdrawal
threshold and thermal withdrawal latency were tested on preoperative day 3 and
postoperative days 1, 3, 5, 7, 10, 14, and 21. Structural changes were examined
by hematoxylin and eosin staining, toluidine blue staining, and electron
microscopy. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were
determined using the thiobarbituric acid and nitroblue tetrazolium methods,
respectively. Nerve growth factor (NGF) expression levels were determined by
immunohistochemistry and Western blot. Intrathecal, but not intraperitoneal,
injection of tempol produced a persistent antinociceptive effect. Intraperitoneal
injection of tempol did not result in high enough concentration of tempol in the
cerebrospinal fluid. Intrathecal, but not intraperitoneal, injection of tempol
inhibited CCI-induced structural damage in the spinal cord reduced MDA levels,
and increased SOD activities in the spinal cord. Furthermore, intrathecal, but
not intraperitoneal, injection of tempol further downregulated the expression of
NGF in the spinal cord following CCI, and this effect was blocked by p38MAPK
inhibitor. Intrathecal injection of tempol produces antinociceptive effects and
reduces CCI-induced structural damage in the spinal cord by increasing SOD
activities and downregulating the expression of NGF via the p38MAPK pathway.
Intraperitoneal administration of tempol does not exhibit antinociceptive
effects.
PMID- 26433733
TI - Annual cost of stable coronary artery disease in France: A modeling study.
AB - BACKGROUND: Few studies have analyzed the cost of treatment of chronic angina
pectoris, especially in European countries. AIM: To determine, using a modeling
approach, the cost of care in 2012 for 1year of treatment of patients with stable
angina, according to four therapeutic options: optimal medical therapy (OMT);
percutaneous coronary intervention with bare-metal stent (PCI-BMS); PCI with drug
eluting stent (PCI-DES); and coronary artery bypass graft (CABG). METHODS: Six
different clinical scenarios that could occur over 1year were defined: clinical
success; recurrence of symptoms without hospitalization; myocardial infarction
(MI); subsequent revascularization; death from non-cardiac cause; and cardiac
death. The probability of a patient being in one of the six clinical scenarios,
according to the therapeutic options used, was determined from a literature
search. A direct medical cost for each of the therapeutic options was calculated
from the perspective of French statutory health insurance. RESULTS: The annual
costs per patient for each strategy, according to their efficacy results, were,
in our models, ?1567 with OMT, ?5908 with PCI-BMS, ?6623 with PCI-DES and ?16,612
with CABG. These costs were significantly different (P<0.05). A part of these
costs was related to management of complications (recurrence of symptoms, MI and
death) during the year (between 3% and 38% depending on the therapeutic options
studied); this part of the expenditure was lowest with the CABG therapeutic
option. CONCLUSION: OMT appears to be the least costly option, and, if reasonable
from a clinical point of view, might achieve appreciable savings in health
expenditure.
PMID- 26433734
TI - The cost-effectiveness of the Olweus Bullying Prevention Program: Results from a
modelling study.
AB - Exposure to bullying affects around 3-5 percent of adolescents in secondary
school and is related to various mental health problems. Many different anti
bullying programmes are currently available, but economic evaluations are
lacking. The aim of this study is to identify the cost effectiveness of the
Olweus Bullying Prevention Program (OBPP). We constructed a decision-tree model
for a Swedish secondary school, using a public payer perspective, and retrieved
data on costs and effects from the published literature. Probabilistic
sensitivity analysis to reflect the uncertainty in the model was conducted. The
base-case analysis showed that using the OBPP to reduce the number of victims of
bullying costs 131,250 Swedish kronor (?14,470) per victim spared. Compared to a
relevant threshold of the societal value of bullying reduction, this indicates
that the programme is cost-effective. Using a relevant willingness-to-pay
threshold shows that the OBPP is a cost-effective intervention.
PMID- 26433735
TI - Sunflower (Helianthus annuus) fatty acid synthase complex: beta-hydroxyacyl-[acyl
carrier protein] dehydratase genes.
AB - MAIN CONCLUSION: Two sunflower hydroxyacyl-[acyl carrier protein] dehydratases
evolved into two different isoenzymes showing distinctive expression levels and
kinetics' efficiencies. beta-Hydroxyacyl-[acyl carrier protein (ACP)]-dehydratase
(HAD) is a component of the type II fatty acid synthase complex involved in 'de
novo' fatty acid biosynthesis in plants. This complex, formed by four
intraplastidial proteins, is responsible for the sequential condensation of two
carbon units, leading to 16- and 18-C acyl-ACP. HAD dehydrates 3-hydroxyacyl-ACP
generating trans-2-enoyl-ACP. With the aim of a further understanding of fatty
acid biosynthesis in sunflower (Helianthus annuus) seeds, two beta-hydroxyacyl
[ACP] dehydratase genes have been cloned from developing seeds, HaHAD1 (GenBank
HM044767) and HaHAD2 (GenBank GU595454). Genomic DNA gel blot analyses suggest
that both are single copy genes. Differences in their expression patterns across
plant tissues were detected. Higher levels of HaHAD2 in the initial stages of
seed development inferred its key role in seed storage fatty acid synthesis. That
HaHAD1 expression levels remained constant across most tissues suggest a
housekeeping function. Heterologous expression of these genes in E. coli
confirmed both proteins were functional and able to interact with the bacterial
complex 'in vivo'. The large increase of saturated fatty acids in cells
expressing HaHAD1 and HaHAD2 supports the idea that these HAD genes are closely
related to the E. coli FabZ gene. The proposed three-dimensional models of HaHAD1
and HaHAD2 revealed differences at the entrance to the catalytic tunnel
attributable to Phe166/Val1159, respectively. HaHAD1 F166V was generated to study
the function of this residue. The 'in vitro' enzymatic characterization of the
three HAD proteins demonstrated all were active, with the mutant having
intermediate K m and V max values to the wild-type proteins.
PMID- 26433736
TI - Incidence of morphometric vertebral fractures in adult patients with growth
hormone deficiency.
AB - Cross-sectional studies showed an elevated prevalence of clinical and
morphometric vertebral fractures (VFs) in adult patients with growth hormone
deficiency (GHD). However, no data are available on incidence and determinants of
radiological VFs in this clinical setting. In this prospective study, we
investigated the incidence and risk factors of radiological VFs in adults with
GHD. Forty patients with GHD (28 males, 12 females; median age 44 years, range 19
82) were studied for incident VFs using quantitative morphometric approach on
spine X-ray at baseline and after 6 years of follow-up. GHD patients were also
studied for bone mineral density (BMD) measured by DXA at lumbar spine. After 6
years of follow-up, 12 patients (30 %) experienced incident VFs. Patients with
incident VFs had more frequently untreated GHD and prevalent VFs at baseline, as
compared to patients who did not experience incident VFs. Untreated GHD patients
were significantly older as compared to treated GHD (50 years, range 19-82 vs. 36
years, range 19-75; p = 0.003), but the correlation between high risk of VFs and
untreated GHD remained significant even after adjustment for the age of patients
(odds ratio 6.8, CI 95 % 1.1-41.8; p = 0.037). In GHD patients experiencing
incident VFs, lumbar spine BMD decreased significantly whereas it did not change
in patients not developing VFs. This is the first prospective study confirming
the hypothesis suggested by cross-sectional studies that untreated GHD may cause
high risk of VFs in adult patients and that recombinant human GH treatment may
effectively decrease such a risk.
PMID- 26433737
TI - Increased serum gamma-glutamyltransferase levels are associated with ventricular
instability in type 2 diabetes.
AB - The purpose of our study is to examine the association between serum GGT levels
and ventricular instability in Chinese patients with T2DM. We conducted a cross
sectional, community-based study in Nanjing, China from June to November 2011.
Among 10,050 patients aged 40-79 years, we enrolled 2444 with pre-diabetes, 2496
with T2DM, and 4521 without diabetes (non-diabetes). Electrocardiograms were
performed to measure the QT interval corrected for heart rate (QTc) and QT
interval dispersion (QTd). Serum GGT levels, metabolic parameters, body mass
index, and blood pressure were also measured. We found that there were no
significant associations of increased QTc/QTd with serum GGT levels in
participants with pre-existing T2DM and non-diabetes, after adjusting for age,
duration of diabetes, and metabolic parameters. Even after adjustment, higher
risks of QTc >= 440 ms/?s and QTd >= 58 ms were found in participants with serum
GGT levels >=49 U/L compared with those with <15 U/L in the pre-diabetes (QTc: OR
1.96, 95 % CI 1.23-2.47; QTd: OR 1.34, 95 % CI 1.07-1.94) and newly diagnosed
T2DM (QTc: OR 2.01, 95 % CI 1.39-2.51; QTd: OR 1.53, 95 % CI 1.03-1.99) groups.
We conclude that Increased serum GGT levels are associated with some markers of
ventricular repolarization abnormalities in the early stage of T2DM.
PMID- 26433738
TI - Factors associated with 1,25-dihydroxyvitamin D3 concentrations in liver
transplant recipients: a prospective observational longitudinal study.
AB - The aim of the study was to identify factors associated with 1,25(OH)2D3
concentrations in liver transplant recipients with emphasis on the renal function
and catabolism. We also tested the hypothesis that tacrolimus increases
1,25(OH)2D3 concentrations. Serum 25(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 were
measured in 41 patients before, at 2 weeks and 3 months after transplantation.
Dose-adjusted tacrolimus concentration was used as a surrogate marker of CYP3A4
activity. Factors associated with 1,25(OH)2D3 were identified using multivariate
linear regression analysis. The median 1,25(OH)2D3 levels remained stable: 55
versus 46 pg/ml (P = 0.36) despite an increase in 25(OH)D3 from 18 ng/ml at
baseline to 26 ng/ml (P = 0.03), serum albumin (34 to 41 g/l, P = 0.02), and
comparable eGFR at baseline and month 3 (94 and 92 ml/min, respectively, P =
0.15). At 3 months 19 % of patients had 1,25(OH)2D3 < 25 pg/ml. Low eGFR and a
low dose-adjusted tacrolimus concentration were both independently associated
with 1,25(OH)2D3 at 3 months. Liver transplant recipients with impaired renal
function or a low dose-adjusted tacrolimus concentration suggesting a high CYP3A4
are at risk of low 1,25(OH)2D3 concentrations. The use of tacrolimus does not
lead to an increase in 1,25(OH)2D3 concentrations in a clinical setting.
PMID- 26433739
TI - Duration of anti-resorptive therapy for osteoporosis.
AB - Osteoporotic fractures are common, and available medications reduce fracture risk
by up to half. However, because the most commonly used drugs, bisphosphonates,
have side effects that may be related to duration of therapy and because long
term efficacy has not been established, the optimal length of treatment has not
been determined. Based on two long-term studies and extensive clinical
experience, a plan is provided to treat patients at risk for 5 years with re
assessment every 2 years thereafter. Assessment tools are limited, but for each
individual, the potential risks and benefits of continuing, discontinuing, re
instituting, or changing therapy can be estimated.
PMID- 26433740
TI - Low 25 (OH) vitamin D levels are associated with autoimmune thyroid disease in
polycystic ovary syndrome.
AB - Low 25(OH) vitamin D levels have been associated with several autoimmune diseases
and recently with autoimmune thyroid disease (AITD). The aim of the study was to
investigate the association of AITD with 25(OH) vitamin D levels in women with
polycystic ovary syndrome (PCOS). Fifty women with PCOS were consecutively
enrolled and underwent routine health checkups, which included measurements of
25(OH) vitamin D, anti-thyroid peroxidase (TPO-Ab), anti-thyreoglobulin (TG-Ab)
antibodies, FT3, FT4, and TSH. Selecting 50 nmol/L as cut-off point, low 25(OH)
vitamin D levels were detected in 23 of 50 patients (46 %). AITD was diagnosed
when TPO-Ab levels exceeding 80 U/ml and/or TG-Ab levels exceeding 70 U/ml. AITD
was detected in 12 of 50 patients (24 %). The levels of 25(OH) vitamin D were
significantly lower in women with PCOS and AITD when compared with women with
PCOS and without AITD (p = 0.02). In women with AITD no correlation was found
between 25(OH) vitamin D and TG-Ab (r = 0.48; p = 0.16), TPO-Ab (r = 0.43; p =
0.21), TSH (r = 0.38; p = 0.27), FT3 (r = -0.40; p = 0.25) and FT4 levels (r =
0.54; p = 0.10). These findings suggest that low levels of 25(OH) vitamin D were
significantly associated with AITD in women with PCOS.
PMID- 26433741
TI - Health risk assessment of heavy metals via dietary intake of wheat grown in
Tianjin sewage irrigation area.
AB - The possible health risks from heavy metal (Zn, Cu, Cr, Ni, Pb, and Cd)
contamination to the local population through the food chain were evaluated in
Tianjin, China, a city with a long history of sewage irrigation. Results showed
that the continuous application of wastewater has led to an accumulation of heavy
metals in the soil, and 54.5 and 18.25% soil samples accumulated Cd and Zn in
concentrations exceeding the permissible limits in China. Concentrations of heavy
metals in wheat grain decreased in the order of Zn > Cu > Cr > Ni > Pb > Cd, and
transfer factors for the six heavy metals showed the trend as Zn > Cd > Cu > Pb >
Cr > Ni. The risk assessment for the six heavy metals through wheat consumption
suggests that concentrations of Cr and Cd in some wheat samples exceed their
reference oral dose for adults and children. In general, no target hazard
quotient value of any individual element was greater than one, which means they
are within the safe interval. However, 36.4 and 63.6% hazard index values for
adults and children were greater than one, respectively. The health risk due to
the added effects of heavy metals was significant for children and adults, and
more attention should be paid tothe potential added threat fromheavy metals to
the health of children via dietary intake of wheat in Tianjin.
PMID- 26433742
TI - An investigation of classical swine fever virus seroprevalence and risk factors
in pigs in Timor-Leste.
AB - Classical swine fever virus (CSFV) is a highly infectious pathogen of pigs and
believed to be a major constraint to pig production in Timor-Leste. The Ministry
of Agriculture and Fisheries conducts vaccination campaigns in an attempt to
control clinical disease, however, there is no empirical data available
concerning the seroprevalence and distribution of CSFV in Timor-Leste. To help
address this knowledge deficit, a cross-sectional study to determine
seroprevalence was conducted in the three districts that border Indonesia. Data
on farmer- and pig-level factors were also collected to look at their impact on
CSFV serological status. Overall, true CSFV seroprevalence was estimated at
34.4%. Seroprevalence estimates varied widely between and within districts,
subdistricts, and villages. Older pigs and pigs that had been vaccinated for CSFV
were more likely to test positive for CSFV antibody. Pigs owned by farmers that
experienced the sudden death of pigs in the 12 months prior to the survey were
more likely to test positive for CSFV antibody, while pigs that had been sick in
the previous three months were less likely to test positive for CSFV antibody.
The final multivariable model accounted for a large amount of variation in the
data, however, much of this variation was explained by the random effects with
less than one percent of the variation explained by the fixed effects. This work
further supports the need for a collaborative approach to whole-island CSFV
control between West Timor, Indonesia and Timor-Leste. Further work is needed to
better understand the risk factors for CSFV serological status in order to
allocate resources for control. As CSFV is now endemic in Timor-Leste research
involving a combination of serology, antigen detection and in-depth investigation
of suspect cases over a period of time may be required.
PMID- 26433743
TI - Medical information concerning an infant's congenital anomaly: Successful
communication to support parental adjustment and transition.
AB - BACKGROUND: When a diagnosis of congenital anomaly (CA) is made, parents are
confronted with new and complex medical information, which may impact their
parental adjustment. However, few studies have explored the role of information
concerning the CA in parental adjustment, during the transition to parenthood.
OBJECTIVE/HYPOTHESIS: This study aimed to characterize both parents' perceptions
of information concerning the CA and to investigate their role in maternal and
paternal adjustment, one month after the disclosure and six months post-birth.
METHODS: Thirty six couples whose infants were prenatally- or postnatally
diagnosed with a CA participated in this prospective longitudinal study. During
both assessment times (Time 1: one-month after the disclosure; Time 2: six-month
post-birth), they answered the Brief Symptom Inventory-18, the EUROHIS-QOL-8, and
other specific questions to assess parents' information perceptions. RESULTS:
Mothers were more satisfied than fathers (p < .01) with the amount of information
that was received at the disclosure, although mothers and fathers reported
similar levels of comprehension of information. Six-month post-birth, both
parents were similarly satisfied with the information that was received, although
mothers sought significantly more (p < .01) additional information. Both maternal
and paternal adjustment were significantly associated with maternal perceptions
of information concerning CA. CONCLUSION: Health professionals should recognize
the important role of information concerning CA in parental adjustment and tailor
their communication practices in order to promote parents' satisfaction and
comprehension of the medical information. Despite the prominent influence of
maternal perceptions on parental adjustment, both parents should be included in
the communication process.
PMID- 26433744
TI - Large-scale signal detection: A unified perspective.
AB - There is an overwhelmingly large literature and algorithms already available on
"large-scale inference problems" based on different modeling techniques and
cultures. Our primary goal in this article is not to add one more new methodology
to the existing toolbox but instead (i) to clarify the mystery how these
different simultaneous inference methods are connected, (ii) to provide an
alternative more intuitive derivation of the formulas that leads to simpler
expressions in order (iii) to develop a unified algorithm for practitioners. A
detailed discussion on representation, estimation, inference, and model selection
is given. Applications to a variety of real and simulated datasets show promise.
We end with several future research directions.
PMID- 26433745
TI - Real-time polymerase chain reaction and culture in the diagnosis of invasive
group B streptococcal disease in infants: a retrospective study.
AB - Group B streptococcus (GBS) is a leading cause of invasive disease in infants.
Accurate and rapid diagnosis is crucial to reduce morbidity and mortality. Real
time polymerase chain reaction (PCR) targeting the dltR gene was utilised for the
direct detection of GBS DNA in blood and cerebrospinal fluid (CSF) from infants
at an Irish maternity hospital. A retrospective review of laboratory and patient
records during the period 2011-2013 was performed in order to evaluate PCR and
culture for the diagnosis of invasive GBS disease. A total of 3570 blood and 189
CSF samples from 3510 infants had corresponding culture and PCR results. Culture
and PCR exhibited concordance in 3526 GBS-negative samples and 13 (25%) GBS
positive samples (n = 53). Six (11%) and 34 (64%) GBS-positive samples were
positive only in culture or PCR, respectively. Culture and PCR identified more
GBS-positive infants (n = 47) than PCR (n = 43) or culture (n = 16) alone. Using
culture as the reference standard, the sensitivity, specificity, and positive and
negative predictive values for PCR on blood samples were 71.4%, 99.2%, 25% and
99.9%, and for CSF samples, they were 60%, 97.8%, 42.9% and 98.9%, respectively.
The sensitivity and positive predictive values were improved (blood: 84.6% and
55%; CSF: 77.8% and 100%, respectively) when maternal risk factors and other
laboratory test results were considered. The findings in this study recommend the
use of direct GBS real-time PCR for the diagnosis of GBS infection in infants
with a clinical suspicion of invasive disease and as a complement to culture, but
should be interpreted in the light of other laboratory and clinical findings.
PMID- 26433747
TI - A report on the consequences of the first implanted device for long-term
analgesia in refractory cancer pain.
AB - BACKGROUND: During the early 1970s, satisfactory long-term treatment of the
severe pain associated with metastatic cancer was not available. Spinal cord
stimulation introduced a few years earlier in 1967 had not proven to be effective
in treating nociceptive pain. We describe our pioneering experience using an
implanted device to infuse local anesthetics into the epidural space and provide
pain relief to the patient. METHODS: Increasing doses of systemic opioids were
unsuccessful in treating the intractable pain of spinal metastases in our
patient. We devised an analgesic delivery system by modifying equipment usually
used for ventriculoperitoneal shunts. A lumbar epidural catheter was inserted in
the patient's spine, then tunneled subcutaneously across the flank to the
anterior abdominal wall, and subsequently connected to a modified Ommaya
reservoir with ventriculoperitoneal shunt tubing. This was filled with local
anesthetic and injected into the patient's epidural space by manual compression.
RESULTS: The system was used for several months with intermittent addition of
local anesthetic to the reservoir with satisfactory control of the patient's
pain. CONCLUSIONS: We describe the first use of an implanted epidural catheter
system for long-term relief of pain due to terminal cancer that occurred at Peter
Bent Brigham Hospital in Boston. We contend that this event played an important
role in the cascade of devices that followed and connect it to the changes in the
attitude of health care providers toward treatment of cancer pain.
PMID- 26433746
TI - Activity of temocillin, mecillinam, ceftazidime, and ceftazidime/avibactam
against carbapenem-non-susceptible Enterobacteriaceae without carbapenemase
production.
AB - Treatment options for multidrug-resistant Gram-negative infections are scarce and
therefore alternatives with a narrow spectrum or new agents are sought.
Antimicrobial susceptibility to temocillin, mecillinam, ceftazidime, and
ceftazidime/avibactam was determined using Etest and disk diffusion according to
European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology.
A total of 77 carbapenem-nonsusceptible Enterobacteriaceae were studied,
including Klebsiella pneumoniae (26%), Escherichia coli (26%), Enterobacter
cloacae (26%), and Enterobacter aerogenes (22%). Several phenotypic tests, PCRs
followed by sequencing and a microbiological bioassay excluded carbapenemase
production in all isolates. Antimicrobial susceptibility rates were low for
temocillin (15.6%, minimum inhibitory concentration [MIC] range 2 to >1,024
MUg/ml), moderate for mecillinam (59.7%, MIC range 0.25 to >256 MUg/ml), and
excellent for ceftazidime/avibactam (100%, zone diameter range 19 to 32 mm,
median 25 mm). 5.2% of the isolates were susceptible to ceftazidime alone (zone
diameter range 6 to 32 mm). In this study, mecillinam exhibited moderate and
ceftazidime/avibactam excellent in vitro antimicrobial activity against
carbapenem-nonsusceptible Enterobacteriaceae without carbapenemase production.
Ceftazidime/avibactam was able to restore previously reduced susceptibility to
ceftazidime in all isolates, thus potentiating its activity. Temocillin only
exhibited low in vitro antimicrobial activity against the isolates. Further
evaluation of mecillinam and ceftazidime/avibactam with regard to the potential
clinical utility against infections caused by these pathogens has to be
performed.
PMID- 26433749
TI - Interactions involved in pH protection of the alphavirus fusion protein.
AB - The alphavirus membrane protein E1 mediates low pH-triggered fusion of the viral
and endosome membranes during virus entry. During virus biogenesis E1 associates
as a heterodimer with the transmembrane protein p62. Late in the secretory
pathway, cellular furin cleaves p62 to the mature E2 protein and a peripheral
protein E3. E3 remains bound to E2 at low pH, stabilizing the heterodimer and
thus protecting E1 from the acidic pH of the secretory pathway. Release of E3 at
neutral pH then primes the virus for fusion during entry. Here we used site
directed mutagenesis and revertant analysis to define residues important for the
interactions at the E3-E2 interface. Our data identified a key residue, E2 W235,
which was required for E1 pH protection and alphavirus production. Our data also
suggest additional residues on E3 and E2 that affect their interacting surfaces
and thus influence the pH protection of E1 during alphavirus exit.
PMID- 26433748
TI - Mungbean yellow mosaic Indian virus encoded AC2 protein suppresses RNA silencing
by inhibiting Arabidopsis RDR6 and AGO1 activities.
AB - RNA silencing refers to a conserved RNA-directed gene regulatory mechanism in a
wide range of eukaryotes. It plays an important role in many processes including
growth, development, genome stability, and antiviral defense in the plants.
Geminivirus encoded AC2 is identified as an RNA silencing suppressor protein,
however, the mechanism of action has not been characterized. In this paper, we
elucidate another mechanism of AC2-mediated suppression activity of Mungbean
Yellow Mosaic India Virus (MYMIV). The AC2 protein, unlike many other
suppressors, does not bind to siRNA or dsRNA species and its suppression activity
is mediated through interaction with key components of the RNA silencing pathway,
viz., RDR6 and AGO1. AC2 interaction inhibits the RDR6 activity, an essential
component of siRNA and tasi-RNA biogenesis and AGO1, the major slicing factor of
RISC. Thus the study identifies dual sites of MYMIV-AC2 interference and probably
accounts for its strong RNA silencing suppression activity.
PMID- 26433750
TI - Electrophysiological evaluation of nerve function in inferior alveolar nerve
injury: relationship between nerve action potentials and histomorphometric
observations.
AB - The objective of this study was to improve the accuracy of diagnosis of inferior
alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the
sensory nerve action potential (SNAP) and sensory nerve conduction velocity
(SCV). Crush and partial and complete nerve amputation injuries were applied to
the IAN of rabbits, then SNAPs and histomorphometric observations were recorded
at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at
5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was
observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an
increase at week 10. For partial nerve amputation, small to medium-sized nerve
fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10.
Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at
week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but
gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable
from week 10, however the SCV was extremely low. This study showed SCV to be an
effective factor in the evaluation of nerve injury and regeneration.
PMID- 26433751
TI - Radiologists' interpretive efficiency and variability in true- and false-positive
detection when screen-reading with tomosynthesis (3D-mammography) relative to
standard mammography in population screening.
AB - We examined interpretive efficiency and variability in true- and false-positive
detection (TP, FP) for radiologists screen-reading with digital breast
tomosynthesis as adjunct to full-field digital mammography (2D/3D) relative to 2D
alone in population-based screening studies. A systematic literature search was
performed to identify screening studies that provided radiologist-specific data
for TP and FP detection. Radiologist interpretive efficiency (trade-off between
TPs and FPs) was calculated using the FP:TP ratio which expresses the number of
FP recalls for each screen-detected breast cancer. We modeled a pooled FP:TP
ratio to assess variability in radiologists' interpretive efficiency at study
level using random effects logistic regression. FP:TP ratio improved (ratio
decreased) for 2D/3D screen-reading (relative to 2D) for a majority of
radiologists (18 of 22) across all studies. Variability in radiologists' FP:TP
ratio was consistently lower in all studies for 2D/3D screen-reading, as
suggested by lower variance in ratios. Study-level pooled FP:TP ratio for 2D- and
2D/3D-mammography respectively, were 5.96 (95%CI: 4.08 to 8.72) and 3.17 (95%CI:
2.25 to 4.47) for the STORM trial; 10.25 (95%CI: 6.42 to 16.35) and 7.07 (95%CI:
4.99 to 10.02) for the Oslo trial; and 20.84 (95%CI: 13.95 to 31.12) and 8.37
(95%CI: 5.87 to 11.93) for the Houston study. This transfers into study-level
improved interpretative efficiencies of 48%, 30% and 55%, respectively, for 2D/3D
screen-reading (relative to 2D). In summary, study-level FP:TP trade-off improved
using 2D/3D-mammography for all studies, which was also seen for most individual
radiologists. There was variability in the FP:TP trade-off between readers and
studies for 2D-as well as for 2D/3D-interpretations but variability in
radiologists' interpretive efficiency was relatively lower using 2D/3D
mammography.
PMID- 26433752
TI - Differences in Caregiver Food Allergy Quality of Life Between Tertiary Care,
Specialty Clinic, and Caregiver-Reported Food Allergic Populations.
AB - BACKGROUND: Food allergy is associated with diminished caregiver quality of life
(QoL), but the heterogeneity of this effect is unknown. OBJECTIVE: The objective
of this study was to explore potential differences in caregiver QoL between self
selected caregivers reporting a child with food allergy (SS) and caregivers with
children followed at a food allergy referral center clinic (RC). METHODS: The
Food Allergy Quality of Life Parental Burden (FAQL-PB) index and screening
questions regarding the child's most severe food reaction were administered to
caregivers of milk, egg, peanut, or tree nut allergic children. SS were recruited
via the email and/or social media networks of 2 large national food allergy
advocacy groups, and RC from a tertiary referral center specialty clinic.
RESULTS: Among 2003 SS and 305 RC, the mean total FAQL-PB QoL score was 2.67.
Compared with SS, RC had a lower (better) mean total QoL score (1.84 vs 2.81, P <
.001), individual FAQL-PB domain scores (mean difference range 0.51-1.93; all P <
.001), and lower QoL scores for all allergens (mean difference range 0.89-1.32;
peanut P < .001, tree nut P < .001, milk P = .006, egg P = .001). In an adjusted
multiple linear regression model, RC were associated with a lower QoL score (-1.6
[95% CI, -1.91 to -1.29], P < .001). Factor analysis of the index revealed 2
dimensions. A minimal clinically important difference of 0.3 was calculated for
the FAQL-PB using the standard error of measurement method. CONCLUSIONS:
Caregiver food allergy QoL is heterogeneous, and worse among SS versus RC.
Clinically and statistically significant differences were noted in the total,
domain-specific, and allergen-specific QoL scores, which indicated that the food
allergic population may be segmented and have different risk profiles and/or
burdens of illness, despite a common diagnosis.
PMID- 26433753
TI - Skeletal muscle electrical stimulation improves baroreflex sensitivity and heart
rate variability in heart failure rats.
AB - The goal of the current study was to evaluate the effects of electrical
stimulation (ES) on the arterial baroreflex sensitivity (BRS) and cardiovascular
autonomic control in rats with chronic heart failure (CHF). Male Wistar rats were
designated to one of four groups: placebo sham (P-Sham, n=9), ES sham (ES-Sham,
n=9), placebo CHF (P-CHF, n=9) or ES CHF (ES-CHF, n=9). The ES was adjusted at a
low frequency (30 Hz), duration of 250 MUs, with hold and rest time of 8s (4
weeks, 30 min/day, 5 times/week). It was applied on the gastrocnemius muscle with
intensity to produce a visible muscle contraction. The rats assigned to the
placebo groups performed the same procedures with the equipment turned off. The
two-way ANOVA and the post hoc Student-Newman-Keuls tests (P<0.05) were used to
data comparison. The BRS was higher in ES-Sham group compared to the P-Sham group
and the ES-CHF group compared to the P-CHF group. ES was able to decrease heart
rate sympatho-vagal modulation and peripheral sympathetic modulation in ES-CHF
compared to P-CHF group. Interestingly, heart rate sympatho-vagal modulation was
similar between ES-CHF and P-Sham groups. Thus, ES enhances heart rate
parasympathetic modulation on heart failure (ES-CHF) compared to placebo (P-CHF),
with consequent decrease of sympatho-vagal balance in the ES-CHF group compared
to the P-CHF. The results show that a 4 week ES protocol in CHF rats enhances
arterial BRS and cardiovascular autonomic control.
PMID- 26433754
TI - Evaluation of performance of human immunodeficiency virus antigen/antibody
combination assays in Taiwan.
AB - BACKGROUND: The fourth-generation human immunodeficiency virus (HIV) combination
assay, which can simultaneously detect the presence of anti-HIV antibody and HIV
antigen, has been shown to shorten the window period in HIV diagnosis compared
with the third-generation HIV antibody immunoassay. This study was aimed to
determine the performance of HIV combination assays in Taiwan, where the HIV-1
seroprevalence is 0.007% and HIV-2 infection has never been reported. METHODS:
Performance of three fourth-generation HIV Ag/Ab combination assays (Dia.Pro,
Wantai, and Bio-Rad) and one third-generation HIV Ab immunoassay (AxSYM HIV 1/2
gO) was assessed. RESULTS: A total of 152 specimens, including 86 confirmed HIV
seropositive and 66 HIV-seronegative samples, were used in the study. The
sensitivity of four assays varied from 98.8% to 100%, and specificity varied from
98.5% to 100%. Performance of the 75 equivocal samples, the HIV status of which
was confirmed later, in terms of negative prediction varied from 81.8% to 87.5%.
The Bio-Rad and Dia.Pro assays exhibited higher sensitivity for the detection of
p24 antigen among the three fourth-generation HIV combination assays. CONCLUSION:
The three fourth-generation HIV Ag/Ab combination assays exhibited better
sensitivity, specificity, and negative prediction than the third-generation HIV
Ab immunoassay.
PMID- 26433755
TI - Virulence factors, antibiotic resistance phenotypes and O-serogroups of
Escherichia coli strains isolated from community-acquired urinary tract infection
patients in Mexico.
AB - BACKGROUND/PURPOSE: Uropathogenic Escherichia coli (UPEC) strains isolated from
patients with community-acquired urinary tract infections (UTIs) were assessed to
determine the prevalence of virulence genes, antibiotic resistance, and the O
serogroup of the strains. METHODS: Consenting patients with community-acquired
UTI were enrolled at Unidad Medica Familiar Number 64 (Instituto Mexicano del
Seguro Social, Estado de Mexico, Mexico) and 321 urine samples were collected.
Polymerase chain reaction (PCR) was used to assess 24 virulence genes and 14 O
serogroups. The Kirby-Bauer method was used to evaluate the antibiotic
susceptibility of the isolated strains to 12 commonly used antibiotics. RESULTS:
A total of 194 strains were identified as E. coli using standard biochemical
tests, followed by PCR amplification of 16S ribosomal RNA gene. Only 58.2% of the
strains belonged to the assessed 14 O-serogroups. The serogroups O25, O15, O8,
and O75 were present in 20.6%, 17%, 6.1%, and 4.6% of strains, respectively. The
most frequently occurring virulence genes among UPEC strains included kpsMT
(92.2% strains), usp (87.1%), irp2 (79.3%), iha (64.9%), fim (61.3%), set (36%),
astA (33.5%), pap (24.7%), and papGII (21.1%). In addition, 97% of the strains
were multi-drug resistant (coresistance to 3-11 antibiotics). CONCLUSION: The
isolated UPEC strains predominantly belonged to three serogroups (O25, O15, and
O8), harboured numerous virulence genes, and are multiresistant to antibiotics.
The findings of this study could be used to orient UTI treatment strategies and
in epidemiological studies in Mexico.
PMID- 26433756
TI - [Comparison of propofol and midazolam on patients undergoing spinal surgery with
intraoperative wake-up test: randomized clinical trial].
AB - BACKGROUND AND OBJECTIVES: Instrumentation in correction operations for spinal
deformities carries a 0.5-5% risk of injuring the spinal cord. The wake-up test
is used for early detection of these injuries. In this study we compared the
effects of propofol and midazolam during wake-up test in scoliosis surgery.
METHODS: Thirty patients were randomly assigned as group P and group M.
Anesthesia was induced with propofol 2.5mgkg(-1) for group P or midazolam
0.5mgkg(-1) for group M with remifentanil 0.5MUgkg(-1) and cisatracurium
0.15mgkg(-1) for both groups. At the maintenance of anesthesia O2/air and
infusions of remifentanil and cisatracurium were used. In group P, propofol 6
10mgkg(-1)h(-1) and in group M, midazolam 0.5mgmgkg(-1) were preferred.
Approximately 15min before the wake-up test, all drugs were discontinued. At the
wake-up test, anesthesiologist asked the patients to open their eyes and squeeze
his/her hand at every 30s until the patients responded. Then patients were told
to wiggle their toes. Hemodynamic parameters, time of eye-opening, appropriate
movement upon verbal command were evaluated. BIS frequency throughout the
operation was recorded. RESULTS: The eye opening time was 9+/-2.15min in group P
and 7+/-3.15min in group M. Motor movement time was 12+/-2.55min in group P and
21.25+/-3.93min in group M. CONCLUSION: Propofol provided better wake-up
conditions and conducted a better neurologic assessment within the same BIS
values than midazolam.
PMID- 26433757
TI - Environmental noise and incident mental health problems: A prospective cohort
study among school children in Germany.
AB - BACKGROUND: Environmental noise is considered a threat to public health as 20% of
the EU population is exposed to health influencing noise levels. An association
of noise and mental health problems in children has been suggested by some
studies, but results are not consistent and there are no longitudinal studies of
this association. Our aim was to investigate the influence of different
environmental noise sources at children's homes on incident mental health
problems in school-aged children. METHOD: A cohort study of children from first
(t0) to fourth grade (t1) of primary school was conducted. Different
environmental noise sources (day/night separately) at children's home were
assessed via parental annoyance reports. Increased noise exposure between t0 and
t1 was the exposure variable. Incident mental health problems were assessed with
the parental version of the Strengths and Difficulties Questionnaire (SDQ). RRs
and 95% CIs were analysed to investigate the association between different noise
sources and incident mental health problems. RESULTS: The study population
consisted of 583 boys and 602 girls. The most common increase in noise exposure
between t0 and t1 was road traffic noise day (26.38%). After adjusting for
covariates exposure to road traffic night was significantly associated with the
total difficulties score (RR=2.06; 95% CI=1.25-3.40), emotional symptoms
(RR=1.69, 95% CI=1.04-2.72), and conduct problems (RR=1.57, 95% CI=1.04-2.38).
Noise by neighbours during the day was associated with conduct problems (RR=1.62,
95% CI=1.11-2.40) and hyperactivity (RR=1.69, 95% CI=1.08-2.65). Aircraft noise
day and construction work day were not associated with any of the SDQ categories
at a significant level. CONCLUSION: Environmental noise is an important public
health problem. This is the first study to investigate the association of a broad
range of noise sources and incident mental health problems in children in a
cohort study. Our results suggest that exposure to noise at children's home is
associated with mental health problems such as emotional symptoms, conduct
problems and hyperactivity.
PMID- 26433758
TI - Attention-deficit hyperactivity disorder, its treatment with medication and the
probability of developing a depressive disorder: A nationwide population-based
study in Taiwan.
AB - OBJECTIVE: The purpose of this study is to determine the risk of developing
depressive disorders by evaluating children with attention-deficit/hyperactivity
disorder (ADHD) in comparison to controls that do not have ADHD, as well as to
analyze whether the medications used to treat ADHD, methylphenidate (MPH) and
atomoxetine (ATX), influence the risk of depression. METHODS: A group of patients
newly diagnosed with ADHD (n=71,080) and age- and gender-matching controls
(n=71,080) were chosen from Taiwan's National Health Insurance database during
the period of January 2000 to December 2011. Both the patients and controls were
monitored through December 31, 2011. We also explore the potential influence of
the length of MPH and ATX treatment on developing depressive disorders. RESULTS:
The ADHD patients showed a significantly increased probability of developing a
depressive disorder when compared to the control group (ADHD: 5.3% vs. CONTROLS:
0.7%; aHR, 7.16, 99% CI: 6.28-8.16). Regarding treatment with MPH, a longer MPH
use demonstrates significant protective effects against developing a depressive
disorder (aOR, 0.91, 99%CI: 0.88-0.94). However, the duration of ATX treatment
could not be significantly correlated with the probability of developing a
depressive disorder. LIMITATIONS: The database employed in this study lacks of
comprehensive clinical information for the patients with ADHD. Potential
moderating factors between ADHD and depression were not considered in-depth in
this study. CONCLUSIONS: The results of this study reveal that youths diagnosed
with ADHD have a greater risk of developing depressive disorders. Long-term
treatment with MPH correlated to the reduced probability of developing a
depressive disorder among youths with ADHD.
PMID- 26433759
TI - Association of Type D personality with increased vulnerability to depression: Is
there a role for inflammation or endothelial dysfunction? - The Maastricht Study.
AB - BACKGROUND: Type D personality - the combination of negative affectivity (NA) and
social inhibition (SI) - has been associated with depression but little is known
about underlying mechanisms. We examined whether (1) Type D is a vulnerability
factor for depression in general, (2) Type D is associated with inflammation or
endothelial dysfunction, and (3) these biomarkers alter the possible association
between Type D and depression. METHODS: In the Maastricht Study, 712 subjects
underwent assessment of NA, SI and Type D personality (DS14), depressive disorder
(Mini-International Neuropsychiatric Interview) and depressive symptoms (Patient
Health Questionnaire-9). Plasma biomarkers of inflammation (hsCRP, SAA, sICAM-1,
IL-6, IL-8, TNF-alpha) and endothelial dysfunction (sVCAM-1, sICAM-1, E-selectin,
vWF) were measured with sandwich immunoassays or ELISA and combined into
standardized sumscores. RESULTS: Regarding personality, 49% of the study
population was low in NA and SI, 22% had SI only, 12% NA only and 17% had Type D.
Depressive disorder and depressive symptoms were significantly more prevalent in
Type D versus the other three personality subgroups. Multivariable regression
analyses showed that Type D was associated with inflammation (beta=0.228,
p=0.014) and endothelial dysfunction (beta=0.216, p=0.022). After adjustment for
these biomarkers, Type D remained independently associated with increased
vulnerability to depressive disorder (OR=13.20, p<0.001) and depressive symptoms
(beta=3.87, p<0.001). LIMITATIONS: The cross-sectional design restrained us to
draw any conclusions on causality. The relatively low prevalence of depressive
disorder restrained us to adjust for more potential confounders. CONCLUSIONS:
Type D personality may be a vulnerability factor for depression, irrespective of
levels of inflammation or endothelial dysfunction. Future research should examine
possible underlying mechanisms.
PMID- 26433760
TI - Altered resting-state functional connectivity in late-life depression: A cross
sectional study.
AB - BACKGROUND: Disrupted brain connectivity is implicated in the pathophysiology of
late-life depression (LLD). There are few studies in this area using resting
state functional magnetic resonance imaging (rs-fMRI). In this pilot case-control
study, we compare rs-fMRI data between age-matched depressed and non-depressed
older adults. METHODS: Older participants (>=55 years) with current major
depressive disorder (MDD) were recruited to participate in an ongoing study of
LLD, and were compared to the age-matched, non-depressed controls. Rs-fMRI data
were collected using a 3-Tesla MRI system. In this study, a data-driven approach
was chosen and an independent component analysis (ICA) was performed. RESULTS:
Seventeen subjects with MDD were compared to 31 controls. The depressed group
showed increased connectivity in three main networks compared to the controls
(p(corr)<0.05), including connectivity between the default mode network (DMN) and
the posterior superior temporal sulcus (pSTS). Increased connectivity was also
observed within the visual network in the medial, lateral and ventral regions of
the occipital lobes, and within the auditory network throughout the right
superior temporal cortex. CONCLUSION: This data-driven, pilot study finds
patterns of increased connectivity that may be unique to LLD in the DMN, as well
as visual and auditory networks. The functional implications of this aberrant
connectivity remains to be determined. These findings should be further explored
in larger samples.
PMID- 26433761
TI - Psychometric properties of the rass scale in the Serbian population.
PMID- 26433763
TI - Clinical effectiveness of cognitive behavioral therapy for depression in routine
care: A propensity score based comparison between randomized controlled trials
and clinical practice.
AB - BACKGROUND: The efficacy of cognitive behavioral therapy (CBT) for the treatment
of depressive disorders has been demonstrated in many randomized controlled
trials (RCTs). This study investigated whether for CBT similar effects can be
expected under routine care conditions when the patients are comparable to those
examined in RCTs. METHOD: N=574 CBT patients from an outpatient clinic were
stepwise matched to the patients undergoing CBT in the National Institute of
Mental Health Treatment of Depression Collaborative Research Program (TDCRP).
First, the exclusion criteria of the RCT were applied to the naturalistic sample
of the outpatient clinic. Second, propensity score matching (PSM) was used to
adjust the remaining naturalistic sample on the basis of baseline covariate
distributions. Matched samples were then compared regarding treatment effects
using effect sizes, average treatment effect on the treated (ATT) and recovery
rates. RESULTS: CBT in the adjusted naturalistic subsample was as effective as in
the RCT. However, treatments lasted significantly longer under routine care
conditions. LIMITATIONS: The samples included only a limited amount of common
predictor variables and stemmed from different countries. There might be
additional covariates, which could potentially further improve the matching
between the samples. CONCLUSIONS: CBT for depression in clinical practice might
be equally effective as manual-based treatments in RCTs when they are applied to
comparable patients. The fact that similar effects under routine conditions were
reached with more sessions, however, points to the potential to optimize
treatments in clinical practice with respect to their efficiency.
PMID- 26433764
TI - Pilot trial of light therapy for depression in hospitalized patients with cystic
fibrosis.
AB - BACKGROUND: Depression is common in cystic fibrosis (CF) and linked with worse
outcomes during hospitalization. Bright-light therapy during hospitalizations
augments antidepressant regimens and reduces length of stay (LOS) in depressed
non-CF patients, but has not been examined in CF METHODS: Thirty subjects used a
light box emitting 10,000lx for 30min each day for 7 straight days following
hospital admission for pulmonary exacerbation. Depressive symptom severity (QIDS
C) and quality of life factors (CFQ-R) were recorded pre/post light therapy.
RESULTS: Eighty percent of subjects had at least mild depressive symptoms upon
admission. Hospitalized CF patients had a significantly lower mean LOS of 11.0+/
3.6 days compared to a historical cohort from the year prior (13.3+/-4.4 days, p
value=0.038). There was a significant decrease in depressive symptoms for all
subjects receiving light therapy (p value<0.0001). There was no relation between
depressive symptoms and lung function or vitamin D. Six out of twelve quality of
life indicators improved with light therapy including the domains of vitality,
emotion, and health perceptions. There were no adverse events reported.
LIMITATIONS: As a pilot study, the design was limited by a lack of a control
group and possible confounding effects of hospitalization treatment on systemic
symptoms. CONCLUSIONS: Light therapy was well tolerated by hospitalized CF
patients and resulted in improved depressive symptoms and quality of life. Light
therapy was associated with a reduced length of stay. Large, randomized trials of
light therapy may be indicated for hospitalized CF patients.
PMID- 26433762
TI - A genome-wide association study of bipolar disorder with comorbid eating disorder
replicates the SOX2-OT region.
AB - BACKGROUND: Bipolar disorder is a heterogeneous mood disorder associated with
several important clinical comorbidities, such as eating disorders. This clinical
heterogeneity complicates the identification of genetic variants contributing to
bipolar susceptibility. Here we investigate comorbidity of eating disorders as a
subphenotype of bipolar disorder to identify genetic variation that is common and
unique to both disorders. METHODS: We performed a genome-wide association
analysis contrasting 184 bipolar subjects with eating disorder comorbidity
against both 1370 controls and 2006 subjects with bipolar disorder only from the
Bipolar Genome Study (BiGS). RESULTS: The most significant genome-wide finding
was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT
(p=8.9*10(-8) for rs4854912) with a secondary peak in the adjacent FXR1 gene
(p=1.2*10(-6) for rs1805576) on chromosome 3q26.33. This region was also the most
prominent finding in the case-only analysis (p=3.5*10(-7) and 4.3*10(-6),
respectively). Several regions of interest containing genes involved in
neurodevelopment and neuroprotection processes were also identified. LIMITATIONS:
While our primary finding did not quite reach genome-wide significance, likely
due to the relatively limited sample size, these results can be viewed as a
replication of a recent study of eating disorders in a large cohort. CONCLUSIONS:
These findings replicate the prior association of SOX2-OT with eating disorders
and broadly support the involvement of neurodevelopmental/neuroprotective
mechanisms in the pathophysiology of both disorders. They further suggest that
different clinical manifestations of bipolar disorder may reflect differential
genetic contributions and argue for the utility of clinical subphenotypes in
identifying additional molecular pathways leading to illness.
PMID- 26433765
TI - Infectious thoracic disease in patients with neutropenia.
PMID- 26433766
TI - A systematic review and meta-analysis of the impact of Spirulina supplementation
on plasma lipid concentrations.
AB - BACKGROUND & AIMS: The impact of Spirulina supplementation on plasma lipid
concentrations has not been conclusively studied. Therefore the aim of the meta
analysis was to assess the effect of Spirulina supplementation on plasma lipid
concentrations. METHODS: We searched PubMed and Scopus (up to July 03, 2015) to
identify randomized controlled trials (RCTs) that investigate the effect
Spirulina supplementation on plasma lipid concentrations. Meta-analysis and meta
regression were performed using random-effects models. RESULTS: Random-effect
meta-analysis of data from 7 RCTs showed a significant effect of supplementation
with spirulina in reducing plasma concentrations of total cholesterol (WMD:
46.76 mg/dL, 95% CI: -67.31 to -26.22, p < 0.001), LDL-C (WMD: -41.32 mg/dL, 95%
CI: -60.62 to -22.03, p < 0.001) and triglycerides (WMD: -44.23 mg/dL, 95% CI:
50.22 to -38.24, p < 0.001), and elevating those of HDL-C (WMD: 6.06 mg/dL, 95%
CI: 2.37-9.76, p = 0.001). The impact of spirulina on plasma concentrations of
total cholesterol (slope: -1.32; 95% CI: -8.58 to 5.93; p = 0.720), LDL-C (slope:
-1.01; 95% CI: -8.03 to 6.02; p = 0.778), triglycerides (slope: -1.39; 95% CI:
4.26 to 1.48; p = 0.342) and HDL-C (slope: 1.79, 95% CI: -0.48 to 4.05; p =
0.122) was independent of administered dose. Regarding duration of
supplementation with Spirulina, significant associations were found with changes
in plasma concentrations of total cholesterol (slope: -1.77; 95% CI: -3.48 to
0.07; p = 0.042), LDL-C (slope: -1.73; 95% CI: -3.40 to -0.06; p = 0.042) HDL-C
(slope: 0.91; 95% CI: 0.68-1.14; p < 0.001) and triglycerides (slope: -1.39; 95%
CI: -2.28 to -0.50; p = 0.002). CONCLUSIONS: This meta-analysis showed a
significant effect of supplementation with Spirulina in reducing plasma
concentrations of total cholesterol, LDL-C, triglycerides and elevating those of
HDL-C.
PMID- 26433767
TI - PURE muscle and more.
PMID- 26433768
TI - Safety of prone positioning still in doubt.
PMID- 26433769
TI - The fate of autogenous free fat grafts in the human temporomandibular joint using
magnetic resonance imaging.
AB - OBJECTIVE: Autologous fat grafts in the temporomandibular joint (TMJ) has
achieved positive clinical effects in preventing adhesion after surgery. However
it still remains indeterminate about the survival rate of grafted fat. The
purpose of this study was to evaluate the long-term survival rate of free fat
grafts in the TMJ using magnetic resonance imaging (MRI). MATERIALS AND METHODS:
89 patients (117 joints) with free fat grafts placed into TMJs following modified
TMJ disc anchor were included in our study. They were divided into the following
groups according to the time lapse between TMJ surgery and the latest MRI
investigation: 1-3 months, 4-6 months, 7-12 months, 13-24 months, and >24 months.
The signal intensity changes and volume retention were evaluated by MRI. RESULTS:
The volume retention rate of grafted free fat showed that the size was hovering
right around 50% although it reduced very slowly with a long-term follow-up.
Nearly half joints showed lower signal intensity of the grafted fat on MRI within
6 months and it recovered to normal compared with that of the day after surgery 6
months later. CONCLUSIONS: Free fat grafted into TMJ cavity could be alive for a
long time with the survival rate about 48.44%. However the survival mechanism has
still been unknown, which need us to explore and study in the future.
PMID- 26433770
TI - Quantifying the outcome of surgical treatment of temporomandibular joint
ankylosis: A systematic review and meta-analysis.
AB - INTRODUCTION: Temporomandibular joint ankylosis results in restricted mouth
opening due to a fibrous or bony (non-neoplastic) union of the mandibular head to
the glenoid fossa. Early surgical treatment is recommended, but the ideal
surgical technique is debated. Our objective was to quantify the effect of
different surgical interventions on maximal (interincisal) mouth opening.
METHODS: The systematic literature search (1960-2015) was based on PubMed, Web of
Science and the Cochrane Library. Pooled mean differences and 95% confidence
intervals between pre-operative and post-operative maximal mouth opening (in mm)
were calculated with random-effects meta-analyses. The surgical interventions
were grouped according to increasing complexity: gap arthroplasty, interposition
arthroplasty and reconstruction arthroplasty. RESULTS: Thirty-eight articles were
identified (1993-2015), including 1215 patients who underwent operations; 84% of
the cases were caused by trauma, and 8% by infection. Gap arthroplasty (n=463),
interposition arthroplasty (n=409) and reconstruction arthroplasty (n=293)
resulted in improved maximal mouth opening of 26.2 mm (95% CI, 24.1-28.2), 26.7
mm (95% CI, 24.6-28.8) and 30.6 mm (95% CI, 28.7-32.5), respectively, and 28.7 mm
overall (95% CI, 26.7-29.2). The mean pooled post-operative maximal mouth opening
ranged between 33.0 and 36.1 mm. CONCLUSIONS: The maximal mouth opening improved
most after reconstruction arthroplasty, and least after gap arthroplasty.
However, the post-operative maximal mouth opening was similar for all techniques.
PMID- 26433771
TI - Development of mandibular osteoradionecrosis in rats: Importance of dental
extraction.
AB - OBJECTIVES: To develop an animal model of mandibular osteoradionecrosis (ORN)
using a high-energy radiation source (as used in human therapeutics) and to
assess the role of tooth extraction on ORN development. MATERIALS AND METHODS
(STUDY DESIGN): Ten animals were irradiated with a single 35- or 50-Gy dose.
Three weeks later, the second left mandibular molar was extracted from three
animals in each group. Nine weeks after irradiation, the animals were euthanized,
with an injection of contrast agent in the bloodstream to highlight
vascularization. Mandibles were harvested and studied using micro-CT, histology,
tartrate-resistant acid phosphatase activity and scanning electron microscopy.
RESULTS: This study demonstrates that a single 50-Gy dose associated with molar
extraction is necessary for ORN development. In these conditions, absence of
healing of the mucosa and bone, dental effects, fibrosis, an increase in
osteoclast activity and a decrease in vascularization were observed. We also
determined that molar extraction increases the impact of the cellular effects of
radiation. CONCLUSION: The mandibular ORN animal model was validated after 50-Gy
irradiation and molar extraction. The results of this study therefore support an
animal ORN model and tissue engineering strategies will now be developed to
regenerate bone for patients with head and neck cancer.
PMID- 26433772
TI - Human parvovirus B19 and autoimmune diseases. Review of the literature and
pathophysiological hypotheses.
AB - A number of arguments support the role played by PVB19 in autoimmunity, in the
broad sense of the term essentially derived from numerous clinical case reports
and/or small series over the past 20-30 years in the medical literature. PVB19
can induce a very broad spectrum of autoantibody production, especially
including: anti-soluble nuclear antigen antibodies, antiphospholipid antibodies
anti-native DNA antibodies, antilymphocyte antibody, anticardiolipin antibodies,
antinuclear antibodies and rheumatoid factor. Notably acute PVB19 infection can
mimic or stimulate autoimmune systemic diseases as rheumatoid arthritis or
systemic lupus erythematosus. However, at the present time, there is no formal
scientific evidence demonstrating a direct role of PVB19 in autoimmunity, bearing
in mind that there are also no formal arguments against it. Further large studies
are needed to understand the eventual role of PVB19 in autoimmune diseases.
PMID- 26433774
TI - A quantitative analysis of microplastic pollution along the south-eastern
coastline of South Africa.
AB - The extent of microplastic pollution (<5mm) in the southern hemisphere,
particularly southern Africa, is largely unknown. This study aimed to evaluate
microplastic pollution along the south-eastern coastline of South Africa, looking
at whether bays are characterised by higher microplastic densities than open
stretches of coastline in both beach sediment and surf-zone water. Microplastic
(mean +/- standard error) densities in the beach sediment ranged between 688.9 +/
348.2 and 3308 +/- 1449 particles . m(-2), while those in the water column
varied between 257.9 +/- 53.36 and 1215 +/- 276.7 particles . m(-3). With few
exceptions there were no significant spatial patterns in either the sediment or
water column microplastic densities; with little differences in density between
bays and the open coast (P>0.05). These data indicate that the presence of
microplastics were not associated with proximity to land-based sources or
population density, but rather is governed by water circulation.
PMID- 26433773
TI - Motivated to win: Relationship between anticipatory and outcome reward-related
neural activity.
AB - Reward-processing involves two temporal stages characterized by two distinct
neural processes: reward-anticipation and reward-outcome. Intriguingly, very
little research has examined the relationship between neural processes involved
in reward-anticipation and reward-outcome. To investigate this, one needs to
consider the heterogeneity of reward-processing within each stage. To identify
different stages of reward processing, we adapted a reward time-estimation task.
While EEG data were recorded, participants were instructed to button-press 3.5s
after the onset of an Anticipation-Cue and received monetary reward for good time
estimation on the Reward trials, but not on No-Reward trials. We first separated
reward-anticipation into event related potentials (ERPs) occurring at three sub
stages: reward/no-reward cue-evaluation, motor-preparation and feedback
anticipation. During reward/no-reward cue-evaluation, the Reward-Anticipation Cue
led to a smaller N2 and larger P3. During motor-preparation, we report, for the
first time, that the Reward-Anticipation Cue enhanced the Readiness Potential
(RP), starting approximately 1s before movement. At the subsequent feedback
anticipation stage, the Reward-Anticipation Cue elevated the Stimulus-Preceding
Negativity (SPN). We also separated reward-outcome ERPs into different components
occurring at different time-windows: the Feedback-Related Negativity (FRN),
Feedback-P3 (FB-P3) and Late-Positive Potentials (LPP). Lastly, we examined the
relationship between reward-anticipation and reward-outcome ERPs. We report that
individual-differences in specific reward-anticipation ERPs uniquely predicted
specific reward-outcome ERPs. In particular, the reward-anticipation Early-RP (1
.8s before movement) predicted early reward-outcome ERPs (FRN and FB-P3),
whereas, the reward-anticipation SPN most strongly predicted a later reward
outcome ERP (LPP). Results have important implications for understanding the
nature of the relationship between reward-anticipation and reward-outcome neural
processes.
PMID- 26433775
TI - Clam predator protection is effective and necessary for food production.
AB - Shellfish aquaculture is a widely practiced way of producing food for human
consumption in coastal areas. When farming intertidal clams, farmers commonly
protect young seedling clams from predatory losses by covering farmed plots with
netting or screening. Recent discussion of the effectiveness of protective nets
or screens and their environmental effects has raised questions concerning the
utility of the practice. We provide data based on a review of more than 35 peer
reviewed articles, as well as our own research that demonstrates the efficacy of
predator protection for clam farms in various habitats around the world. In
addition, we evaluate the effects of screening on temperature, and comment on
ancient practices of clam gardening as conducted in the Pacific Northwest.
PMID- 26433777
TI - Sleep Violence.
PMID- 26433776
TI - Measurement properties of patient-reported outcome measures (PROMs) in adults
with obstructive sleep apnea (OSA): A systematic review.
AB - This systematic review summarizes the evidence regarding the quality of patient
reported outcome measures (PROMs) validated in patients with obstructive sleep
apnea (OSA). We performed a systematic literature search of all PROMs validated
in patients with OSA, and found 22 measures meeting our inclusion criteria. The
quality of the studies was assessed using the consensus-based standards for the
selection of health status measurement instruments (COSMIN) checklist. The
results showed that most of the measurement properties of the PROMs were not, or
not adequately, assessed. For many identified PROMs there was no involvement of
patients with OSA during their development or before the PROM was tested in
patients with OSA. Positive exceptions and the best current candidates for
assessing health status in patients with OSA are the sleep apnea quality of life
index (SAQLI), Maugeri obstructive sleep apnea syndrome (MOSAS) questionnaire,
Quebec sleep questionnaire (QSQ) and the obstructive sleep apnea patient-oriented
severity index (OSAPOSI). Even though there is not enough evidence to fully judge
the quality of these PROMs as outcome measure, when interpreted with caution,
they have the potential to add value to clinical research and clinical practice
in evaluating aspects of health status that are important to patients.
PMID- 26433778
TI - Experimental and numerical characterization of the water flow in spacer-filled
channels of spiral-wound membranes.
AB - Micro-scale flow distribution in spacer-filled flow channels of spiral-wound
membrane modules was determined with a particle image velocimetry system (PIV),
aiming to elucidate the flow behaviour in spacer-filled flow channels. Two
dimensional water velocity fields were measured in a flow cell (representing the
feed spacer-filled flow channel of a spiral wound reverse osmosis membrane module
without permeate production) at several planes throughout the channel height. At
linear flow velocities (volumetric flow rate per cross-section of the flow
channel considering the channel porosity, also described as crossflow velocities)
used in practice (0.074 and 0.163 m.s(-1)) the recorded flow was laminar with
only slight unsteadiness in the upper velocity limit. At higher linear flow
velocity (0.3 m.s(-1)) the flow was observed to be unsteady and with
recirculation zones. Measurements made at different locations in the flow cell
exhibited very similar flow patterns within all feed spacer mesh elements, thus
revealing the same hydrodynamic conditions along the length of the flow channel.
Three-dimensional (3-D) computational fluid dynamics simulations were performed
using the same geometries and flow parameters as the experiments, based on steady
laminar flow assumption. The numerical results were in good agreement (0.85-0.95
Bray-Curtis similarity) with the measured flow fields at linear velocities of
0.074 and 0.163 m.s(-1), thus supporting the use of model-based studies in the
optimization of feed spacer geometries and operational conditions of spiral wound
membrane systems.
PMID- 26433779
TI - Using UV-vis absorbance spectral parameters to characterize the fouling
propensity of humic substances during ultrafiltration.
AB - Ultrafiltration (UF) can achieve excellent removal of natural organic matter
(NOM), but the main challenge for this process is the limited understanding of
membrane fouling. The objective of this study is to explore the potential of UV
vis spectroscopic analysis for the detection of membrane fouling caused by humic
acids (HA) at different solution chemistries (i.e., calcium ions (Ca(2+)) and
pH). In the presence of Ca(2+), several spectral parameters, including the
DSlope(325-375) (the slope of the log-transformed absorbance spectra over 325-375
nm), S(275-295) (the slope of the absorption coefficient over 257-295 nm) and
S(R) (the ratio of S(275-295) to S(350-400)) of various HA solutions, were
correlated with the molecule aggregation and the membrane fouling potential.
Interestingly, increased DSlope(325-375) and decreased S(275-295) and S(R) were
observed for the HA-Ca(2+) interaction under alkaline conditions (i.e., pH = 9)
relative to those in lower pH environments (i.e., pH = 7 or 6), suggesting that
spectral parameters were able to predict HA-Ca(2+) interactions under varying pH
conditions. The strong correlations between the spectral parameters and the
unified membrane fouling index (UMFI) obtained from UF experiments further
corroborated that the spectral parameters were able to predict the membrane
fouling potential. Moreover, the spectral parameters were also found to well
reveal the fouling extent of the mixture of HA and Suwannee River NOM (SRNOM) or
the pure SRNOM added with varying calcium concentrations, implying that the
spectroscopic analysis was also available for the indication of practical NOM
fouling. In addition, the measurement of S(275-295) and S(R) of the permeate
solution suggests an increasing proportion of small-molecule HA in the permeate
during the UF process. This study not only expands our knowledge of NOM-Ca(2+)
aggregates as well as their role in membrane fouling behavior but also provides
an approach for the in situ characterization of membrane performance.
PMID- 26433780
TI - Database on natural polymorphisms and resistance-related non-synonymous mutations
in thymidine kinase and DNA polymerase genes of herpes simplex virus types 1 and
2.
AB - The use of genotypic resistance testing of herpes simplex virus types 1 and 2
(HSV-1 and HSV-2) is increasing because the rapid availability of results
significantly improves the treatment of severe infections, especially in
immunocompromised patients. However, an essential precondition is a broad
knowledge of natural polymorphisms and resistance-associated mutations in the
thymidine kinase (TK) and DNA polymerase (pol) genes, of which the DNA polymerase
(Pol) enzyme is targeted by the highly effective antiviral drugs in clinical use.
Thus, this review presents a database of all non-synonymous mutations of TK and
DNA pol genes of HSV-1 and HSV-2 whose association with resistance or natural
gene polymorphism has been clarified by phenotypic and/or functional assays. In
addition, the laboratory methods for verifying natural polymorphisms or
resistance mutations are summarized. This database can help considerably to
facilitate the interpretation of genotypic resistance findings in clinical HSV-1
and HSV-2 strains.
PMID- 26433782
TI - Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of
cadazolid and vancomycin in C. difficile infection.
AB - OBJECTIVES: The aim of this study was to evaluate the susceptibilities of
Clostridium difficile isolates to cadazolid, a novel antibiotic for the treatment
of C. difficile infection. METHODS: Ribotyping and susceptibilities were
determined for C. difficile isolates from a multicentre, double-blind, Phase 2
study of oral cadazolid in patients with C. difficile infection (NCT01222702,
ClinicalTrials.gov; EudraCT 2010-020941-29, European Clinical Trials Database).
Patients were randomized to receive 250, 500 or 1000 mg of cadazolid twice daily
or 125 mg of vancomycin four times daily, for 10 days. MICs of cadazolid,
vancomycin, fidaxomicin, linezolid and moxifloxacin were determined at baseline
for all patients and post-baseline for patients with clinical failure or
recurrence, using the agar dilution method. RESULTS: Seventy-eight of 84 patients
had an evaluable toxigenic C. difficile isolate at baseline. The most frequent
PCR ribotype was 027 (15.4%). Cadazolid MICs for baseline isolates (including
epidemic strain 027) ranged from 0.06 to 0.25 mg/L. Baseline cadazolid MICs were
similar to those of fidaxomicin and lower than those of vancomycin, linezolid and
moxifloxacin. For each clinical outcome group (clinical cure, clinical failure,
sustained clinical response and clinical failure or recurrence), the baseline
cadazolid MIC range was 0.06-0.25 mg/L. Mean (min-max) cadazolid faecal
concentration (MUg/g) on day 5 was 884 (101-2710), 1706 (204-4230) and 3226 (1481
12 600) for the doses 250, 500 and 1000 mg, respectively. CONCLUSIONS: For all
cadazolid doses, the faecal concentration was in excess of several thousand-fold
the MIC90 for C. difficile. The MIC of cadazolid for all C. difficile isolates,
including epidemic strains, was low and in the same narrow range regardless of
treatment outcome.
PMID- 26433781
TI - Rhesus theta-defensin-1 (RTD-1) exhibits in vitro and in vivo activity against
cystic fibrosis strains of Pseudomonas aeruginosa.
AB - OBJECTIVES: Chronic endobronchial infections with Pseudomonas aeruginosa
contribute to bronchiectasis and progressive loss of lung function in patients
with cystic fibrosis. This study aimed to evaluate the therapeutic potential of a
novel macrocyclic peptide, rhesus theta-defensin-1 (RTD-1), by characterizing its
in vitro antipseudomonal activity and in vivo efficacy in a murine model of
chronic Pseudomonas lung infection. METHODS: Antibacterial testing of RTD-1 was
performed on 41 clinical isolates of P. aeruginosa obtained from cystic fibrosis
patients. MIC, MBC, time-kill and post-antibiotic effects were evaluated
following CLSI-recommended methodology, but using anion-depleted Mueller-Hinton
broth. RTD-1 was nebulized daily for 7 days to cystic fibrosis transmembrane
conductance regulator (CFTR) F508del-homozygous mice infected using the agar bead
model of chronic P. aeruginosa lung infection. In vivo activity was evaluated by
change in lung bacterial burden, airway leucocytes and body weight. RESULTS: RTD
1 exhibited potent in vitro bactericidal activity against mucoid and non-mucoid
strains of P. aeruginosa (MIC90 = 8 mg/L). Cross-resistance was not observed when
tested against MDR and colistin-resistant isolates. Time-kill studies indicated
very rapid, concentration-dependent bactericidal activity of RTD-1 with >=3 log10
cfu/mL reductions at concentrations >=4* MIC. No post-antibiotic effect was
observed. In vivo, nebulized treatment with RTD-1 significantly decreased lung P.
aeruginosa burden (mean difference of -1.30 log10 cfu; P = 0.0061), airway
leucocytes (mean difference of -0.37 log10; P = 0.0012) and weight loss (mean
difference of -12.62% at day 7; P < 0.05) when compared with controls.
CONCLUSIONS: This study suggests that RTD-1 is a promising potential therapeutic
agent for cystic fibrosis airway disease.
PMID- 26433784
TI - Comparative evaluation of the hydrogen production by mixed consortium, synthetic
co-culture and pure culture using distillery effluent.
AB - Wastewater comprises of various carbon sources. So, the use of microbial
consortium may improve the hydrogen production and organic reduction. The present
study deals with biohydrogen production by acidogenic mixed consortia (AMC),
synthetic co-culture (Klebsiella pneumoniae IIT-BT 08 and Citrobacter freundii
IIT-BT L139) and pure culture using distillery effluent (DE). Higher hydrogen
yield was observed in case of AMC (9.17 mol/kg CODreduced) as compared to the
synthetic co-culture and pure culture. PCR-DGGE analysis indicated that the
consortium was predominated by species closely affiliated to Clostridium sp. The
average hydrogen production rate was 267 mL/Lh. The maximum hydrogen production
rate (Rm), hydrogen production potential (P) and lag time (lambda) by AMC using
DE were 507.2 mL/Lh, 3729 m/L and 2.04 h, respectively. Maximum gaseous energy
recovery by AMC was found to be higher by 21.9% and 45.4% than that of using co
culture and pure culture respectively.
PMID- 26433785
TI - Non-severe thermochemical hydrolysis of stover from white corn and sequential
enzymatic saccharification and fermentation to ethanol.
AB - A parametric study, with an initial load of 15%w/w of dry stover from white corn,
was conducted to evaluate the sequential thermochemical hydrolysis (TH),
enzymatic saccharification (ES) and fermentation of the whole slurry with
ethanologenic Escherichia coli. The TH was designed to release the maximum amount
of xylose with a concomitant formation of minimal amounts of furans. It was found
that 29.0% or 93.2% of the xylan was recovered as free xylose at 130 degrees C
after 8 min in the presence of 1% or 2%w/w H2SO4 and produced only 0.06 or 0.44
g/L of total furans, respectively. After 24h of ES, 76.14-77.18 g/L of
monosaccharides (pentoses and hexoses) were obtained. These slurries, which
contained 0.03-0.26 g/L of total furans and 5.14-5.91 g/L of acetate, were
fermented with 3.7 g/L of ethanologenic E. coli to produce 24.5-23.5 g/L of
ethanol.
PMID- 26433786
TI - Cultivation of Chlorella vulgaris JSC-6 with swine wastewater for simultaneous
nutrient/COD removal and carbohydrate production.
AB - Swine wastewater, containing a high concentration of COD and ammonia nitrogen, is
suitable for the growth of microalgae, leading to simultaneous COD/nutrients
removal from the wastewater. In this study, an isolated carbohydrate-rich
microalga Chlorella vulgaris JSC-6 was adopted to perform swine wastewater
treatment. Nearly 60-70% COD removal and 40-90% NH3-N removal was achieved in the
mixotrophic and heterotrophic culture, depending on the dilution ratio of the
wastewater, while the highest removal percentage was obtained with 20-fold
diluted wastewater. Mixotrophic cultivation by using fivefold diluted wastewater
resulted in the highest biomass concentration of 3.96 g/L. The carbohydrate
content of the microalga grown on the wastewater can reach up to 58% (per dry
weight). The results indicated that the microalgae-based wastewater treatment can
efficiently reduce the nutrients and COD level, and the resulting microalgal
biomass had high carbohydrate content, thereby having potential applications for
the fermentative production of biofuels or chemicals.
PMID- 26433783
TI - Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill
patients associated with improved pharmacokinetic/pharmacodynamic and patient
outcomes? An observation from the Defining Antibiotic Levels in Intensive care
unit patients (DALI) cohort.
AB - OBJECTIVES: We utilized the database of the Defining Antibiotic Levels in
Intensive care unit patients (DALI) study to statistically compare the
pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion
and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in
critically ill patients using inclusion criteria similar to those used in
previous prospective studies. METHODS: This was a post hoc analysis of a
prospective, multicentre pharmacokinetic point-prevalence study (DALI), which
recruited a large cohort of critically ill patients from 68 ICUs across 10
countries. RESULTS: Of the 211 patients receiving piperacillin/tazobactam and
meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182)
of patients achieved the most conservative target of 50% fT>MIC (time over which
unbound or free drug concentration remains above the MIC). Decreasing creatinine
clearance and the use of prolonged infusion significantly increased the PTA for
most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had
respiratory infection, patients receiving beta-lactams via prolonged infusion
demonstrated significantly better 30 day survival when compared with intermittent
bolus patients [86.2% (25/29) versus 56.7% (17/30); P = 0.012]. Additionally, in
patients with a SOFA score of >=9, administration by prolonged infusion compared
with intermittent-bolus dosing demonstrated significantly better clinical cure
[73.3% (11/15) versus 35.0% (7/20); P = 0.035] and survival rates [73.3% (11/15)
versus 25.0% (5/20); P = 0.025]. CONCLUSIONS: Analysis of this large dataset has
provided additional data on the niche benefits of administration of
piperacillin/tazobactam and meropenem by prolonged infusion in critically ill
patients, particularly for patients with respiratory infections.
PMID- 26433787
TI - Biophotonic perception on Desmodesmus sp. VIT growth, lipid and carbohydrate
content.
AB - Constant and fluctuating light intensity significantly affects the growth and
biochemical composition of microalgae and it is essential to identify suitable
illumination conditions for commercial microalgae biofuel production. In the
present study, effects of light intensities, light:dark cycles, incremental light
intensity strategies and fluctuating light intensities simulating different sky
conditions in indoor photobioreactor on Desmodesmus sp. VIT growth, lipid and
carbohydrate content were analyzed in batch culture. The results revealed that
Desmodesmus sp. VIT obtained maximum lipid content (22.5%) and biomass production
(1.033 g/L) under incremental light intensity strategy. The highest carbohydrate
content of 25.4% was observed under constant light intensity of 16,000 lx and
16:08 h light:dark cycle. The maximum biomass productivity of Desmodesmus sp. VIT
(53.38 mg/L/d) was occurred under fluctuating light intensity simulating
intermediate overcast sky condition.
PMID- 26433789
TI - Kinetic analysis of two-phase enzymatic hydrolysis of hemicellulose of xylan
type.
AB - We present a coupled experimental and theoretical framework for quantifying the
kinetics of two-phase enzymatic hydrolysis of hemicellulose. For xylan loading of
1-5mg/ml, the nature of inhibition by the product xylose (non-competitive), the
kinetic constants (Km=3.93 mg/ml, Vmax=0.0252 mg/ml/min) and the xylose
inhibition constant (Kx=0.122 mg/ml) are experimentally determined. Our multi
step two-phase kinetic model incorporating enzyme adsorption to the solid
substrate and non-competitive product inhibition is simulated using our kinetic
data and validated against our experimentally measured temporal dynamics of
xylose and reducing sugars. Further experiments show that higher substrate
loading reduces the specific adsorption of the endoxylanase to the solid xylan
and the enzyme's solid-liquid distribution ratio, which decelerates the solid
hydrolysis and accelerates the liquid phase reactions. Thus, the xylose yield
increases with substrate loading, which increases product inhibition and
decreases reducing sugar yields. An operating cost analysis gives 3mg/ml as the
optimal substrate loading.
PMID- 26433788
TI - Thermogravimetric characterization and gasification of pecan nut shells.
AB - This study focuses on the evaluation of pecan nut shells as an alternative source
of energy through pyrolysis and gasification. The physicochemical characteristics
of the selected biomass that can influence the process efficiency, consumption
rates, and the product yield, as well as create operational problems, were
determined. In addition, the thermal decomposition kinetics necessary for
prediction of consumption rates and yields were determined. Finally, the
performance of a downdraft gasifier fed with pecan nut shells was analyzed in
terms of process efficiency and exit gas characteristics. It was found that the
pyrolytic decomposition of the nut shells can be modeled adequately using a
single equation considering two independent parallel reactions. The performance
of the gasification process can be influenced by the particle size and air flow
rate, requiring a proper combination of these parameters for reliable operation
and production of a valuable syngas.
PMID- 26433790
TI - Production of optically pure L-lactic acid from lignocellulosic hydrolysate by
using a newly isolated and D-lactate dehydrogenase gene-deficient Lactobacillus
paracasei strain.
AB - The use of lignocellulosic feedstock for lactic acid production with a difficulty
is that the release of inhibitory compounds during the pretreatment process which
inhibit the growth of microorganism. Thus we report a novel lactic acid
bacterium, Lactobacillus paracasei 7 BL, that has a high tolerance to inhibitors
and produced optically pure l-lactic acid after the interruption of ldhD gene.
The strain 7 BL fermented glucose efficiently and showed high titer of l-lactic
acid (215 g/l) by fed-batch strategy. In addition, 99 g/l of l-lactic acid with
high yield (0.96 g/g) and productivity (2.25-3.23 g/l/h) was obtained by using
non-detoxified wood hydrolysate. Rice straw hydrolysate without detoxification
was also tested and yielded a productivity rate as high as 5.27 g/l/h. Therefore,
L. paracasei 7 BL represents a potential method of l-lactic acid production from
lignocellulosic biomass and has attractive application for industries.
PMID- 26433791
TI - Efficient magnesium lactate production with in situ product removal by
crystallization.
AB - In this paper, attempts were made to develop an in situ product removal process
for magnesium lactate production based on crystallization. The crystallization
was conducted at 42 degrees C without seed crystal addition. The product
concentration, productivity and yield of fermentation coupled with in situ
product removal (ISPR) reached 143 g L(-1), 2.41 g L(-1)h(-1) and 94.3%. In four
cycles of crystallization, the average reuse rate of fermentation medium and
removal rate of product reached 64.0% and 77.7%. At the same time, ISPR
fermentation saved 40% water, 41% inorganic salts and 43% yeast extract (YE) as
compared to fed-batch fermentation. The process introduces an effective way to
reduce the amount of waste water and the raw material cost in magnesium lactate
fermentation.
PMID- 26433792
TI - Open fermentative production of L-lactic acid using white rice bran by
simultaneous saccharification and fermentation.
AB - To reduce raw material cost for lactic acid production, white rice bran as an
important byproduct in rice milling, was used in l-lactic acid production by open
simultaneous saccharification and fermentation (SSF). Although one thermotolerant
strain was used at a temperature as high as 50 degrees C, the open fermentation
was still inefficient due to the indigenous thermophilic bacteria from corn steep
liquor powder. A stepwise controlled pH was proposed in open SSF process, and no
complicated pretreatment or sterilization was needed before fermentation. In
batch fermentation, 117 gL(-1) lactic acid was obtained, and the productivity and
yield reached 2.79 gL(-1) h(-1) and 98.75%, respectively. These results showed an
efficient way to develop high value-added products from white rice bran.
PMID- 26433793
TI - Economic analysis and environmental impact assessment of three different
fermentation processes for fructooligosaccharides production.
AB - Three different fermentation processes for the production of
fructooligosaccharides (FOS) were evaluated and compared in terms of economic
aspects and environmental impact. The processes included: submerged fermentation
of sucrose solution by Aspergillus japonicus using free cells or using the cells
immobilized in corn cobs, and solid-state fermentation (SSF) using coffee
silverskin as support material and nutrient source. The scale-up was designed
using data obtained at laboratory scale and considering an annual productivity
goal of 200 t. SSF was the most attractive process in both economic and
environmental aspects since it is able to generate FOS with higher annual
productivity (232.6 t) and purity (98.6%) than the other processes; reaches the
highest annual profit (6.55 M?); presents the lowest payback time (2.27 years);
and is more favourable environmentally causing a lower carbon footprint (0.728
kg/kg, expressed in mass of CO2 equivalent per mass of FOS) and the lowest
wastewater generation.
PMID- 26433794
TI - Synergistic action of recombinant accessory hemicellulolytic and pectinolytic
enzymes to Trichoderma reesei cellulase on rice straw degradation.
AB - Synergism between core cellulases and accessory hydrolytic/non-hydrolytic enzymes
is the basis of efficient hydrolysis of lignocelluloses. In this study, the
synergistic action of three recombinant accessory enzymes, namely GH62 alpha-l
arabinofuranosidase (ARA), CE8 pectin esterase (PET), and GH10 endo-1,4-beta
xylanase (XYL) from Aspergillus aculeatus expressed in Pichia pastoris to a
commercial Trichoderma reesei cellulase (Accellerase(r) 1500; ACR) on hydrolysis
of alkaline pretreated rice straw was studied using a mixture design approach.
Applying the full cubic model, the optimal ratio of quaternary enzyme mixture was
predicted to be ACR:ARA:PET:XYL of 0.171:0.079:0.100:0.150, which showed a
glucose releasing efficiency of 0.173 gglc/FPU, higher than the binary ACR:XYL
mixture (0.122 gglc/FPU) and ACR alone (0.081 gglc/FPU) leading to a 47.3%
increase in glucose yield compared with that from ACR at the same cellulase
dosage. The result demonstrates the varying degree of synergism of accessory
enzymes to cellulases useful for developing tailor-made enzyme systems for bio
industry.
PMID- 26433795
TI - Move more and sit less: regular physical activity improves mobility in older age.
PMID- 26433796
TI - Development of a self-administrated quality of life questionnaire for sarcopenia
in elderly subjects: the SarQoL.
AB - BACKGROUND: The impact of sarcopenia on quality of life is currently assessed by
generic tools. However, these tools may not detect subtle effects of this
specific condition on quality of life. OBJECTIVE: The aim of this study was to
develop a sarcopenia-specific quality of life questionnaire (SarQoL, Sarcopenia
Quality of Life) designed for community-dwelling elderly subjects aged 65 years
and older. SETTINGS: Participants were recruited in an outpatient clinic in
Liege, Belgium. SUBJECTS: Sarcopenic subjects aged 65 years or older. METHODS:
The study was articulated in the following four stages: (i) Item generation-based
on literature review, sarcopenic subjects' opinion, experts' opinion, focus
groups; (ii) Item reduction-based on sarcopenic subjects' and experts'
preferences; (iii) Questionnaire generation-developed during an expert meeting;
(iv) Pretest of the questionnaire-based on sarcopenic subjects' opinion. RESULTS:
The final version of the questionnaire consists of 55 items translated into 22
questions rated on a 4-point Likert scale. These items are organised into seven
domains of dysfunction: Physical and mental health, Locomotion, Body composition,
Functionality, Activities of daily living, Leisure activities and Fears. In view
of the pretest, the SarQoL is easy to complete, independently, in ~10 min.
CONCLUSIONS: The first version of the SarQoL, a specific quality of life
questionnaire for sarcopenic subjects, has been developed and has been shown to
be comprehensible by the target population. Investigations are now required to
test the psychometric properties (internal consistency, test-retest reliability,
divergent and convergent validity, discriminant validity, floor and ceiling
effects) of this questionnaire.
PMID- 26433797
TI - Evidence on Acupuncture and Pain: Reporting on a Work in Progress.
PMID- 26433798
TI - As Acupressure Decreases Pain, Acupuncture May Improve Some Aspects of Quality of
Life for Women with Primary Dysmenorrhea: A Systematic Review with Meta-Analysis.
AB - Primary dysmenorrhea is the most common gynecological symptom reported by women
and constitutes a high health, social, and economic burden. Chemotherapies, along
with their side effects, have not yielded satisfactory outcomes. Alternative
nonpharmacological interventions, including acupuncture and acupressure, have
been advocated, but evidence regarding their beneficial effect is inconclusive.
This study sought to obtain evidence on the effectiveness of acupuncture and
acupressure interventions. Twelve electronic databases were searched by using
menstrual pain intensity and quality of life as primary and secondary outcomes,
respectively, with the PEDro guideline for quality appraisal. Data unsuitable for
a meta-analysis were reported as descriptive data. The search yielded 38
citations, from which eight studies were systematically reviewed, four of the
eight being eligible for meta-analysis. The systematic review showed moderate
methodological quality with a mean of 6.1 out of 10 on the PEDro quality scale.
Acupressure showed evidence of pain relief while acupuncture improved both the
mental and the physical components of quality of life. In conclusion,
physiotherapists should consider using acupuncture and acupressure to treat
primary dysmenorrhea, but a need exists for higher quality, randomized, blinded,
sham-controlled trials with adequate sample sizes to establish clearly the
effects of these modalities.
PMID- 26433799
TI - Efficacies of Acupuncture and Anti-inflammatory Treatment for Carpal Tunnel
Syndrome.
AB - This study compared the efficacies of acupuncture and anti-inflammatory treatment
in patients with carpal tunnel syndrome (CTS). Fifty patients with mild to
moderate CTS were randomly divided into two groups. Both groups received night
wrist splints as the standard conservative treatment for 1 month. The acupuncture
group also received eight sessions of acupuncture therapy (twice a week for 4
weeks). The control group received 400 mg of ibuprofen three times a day for 10
days. The visual analog scale (VAS) score, the score on the Boston Carpal Tunnel
Questionnaire for Functional Status and Symptom Severity (BCTQ FUNCT and SYMPT),
and the electrodiagnostic findings were evaluated at baseline and 1 month after
treatment. At the final follow up, significant improvements were found in both
groups (p < 0.05). Statistically significant improvements were observed in the
VAS score, the score on the global BCTQ FUNCT and SYMPT, and the
electrodiagnostic findings, but not in the distal motor latency (DML), in the
acupuncture group (p < 0.05). Our findings indicate that acupuncture affected the
score on the global BCTQ FUNCT and SYMPT, the VAS score, and the
electrodiagnostic findings, except the DML, more than ibuprofen did and that
acupuncture might be an effective treatment for CTS.
PMID- 26433800
TI - Inhibitory Effects of Scolopendra Pharmacopuncture on the Development and
Maintenance of Neuropathic Pain in Rats: Possible Involvement of Spinal Glial
Cells.
AB - Scolopendra extracts were used for pharmacopuncture at the Kidney 1 acupoint to
investigate the role of Scolopendra pharmacopuncture (SPP) in both the
development and maintenance of neuropathic pain induced by L5 spinal nerve
ligation in rats and the contribution of spinal glial cells. A single treatment
and five once-daily treatments with SPP were given to evaluate its effects on the
development and maintenance stages of neuropathic pain, respectively, which was
followed by behavioral tests. Immunohistochemistry and Western blotting tests
were also carried out. A single treatment of SPP delayed spinal nerve ligation
induced mechanical allodynia and thermal hyperalgesia and induced a profound
decrease in the expression of ionized calcium binding adaptor protein in the
lumbar spinal cord. Repeated SPP treatments reliably suppressed mechanical
allodynia and thermal hyperalgesia at later time points, and these results
correlated mainly with decreases in glial fibrillary acidic protein.
Intriguingly, ionized calcium binding adaptor protein expression was also reduced
after repeated SPP. These results illustrate that neuropathic pain in the
development and maintenance stages is alleviated by SPP treatment, which may be
ascribed principally to deactivations of microglia and astroglia, respectively.
Additionally, microglial inactivation seems to be partially involved in
preventing neuropathic pain in the maintenance stage.
PMID- 26433801
TI - The Effects of Acupuncture on Peripheral Facial Palsy Sequelae after 20 Years via
Electromyography.
AB - OBJECTIVE: This research used electromyography to evaluate the effects of
acupuncture on facial palsy peripheral sequelae. METHODS: The 44-year-old woman
who participated in this study presented sequelae resulting from 20 years of
peripheral facial nerve palsy (FNP) on the right side and synkinesis in the left
eye. In electromyography, the electrodes were positioned on the motor points over
the orbicularis oris and the orbicularis oculi muscles to establish myofunctional
feedback prior to and after rehabilitation, which consisted of 20-minute sessions
of acupuncture once per week for 20 weeks: using manual stimulation at acupoints
Yintang, LR3, GB21, CV17, ST2, ST3, ST6, ST7, GB2, and SI19; and Tou-Kuang-Min
and ST4 using electrical stimulation with a 4-Hz pulsed current. The subjective
pain intensities were recorded. RESULTS: The root-mean-square (RMS)
electromyographic comparative analysis showed greater activation and recruitment
of muscle fibers on the right side and a reduced overload on the left side, which
promoted a functional evolution of movements and a positive response in the
stomatognathic system. CONCLUSION: Acupuncture associated with electrical
stimulation reversed the peripheral facial paralysis in a short time. Severe
sequelae were minimized due to the balance of muscle activation in response to
the electrical stimulation provided by the acupuncture needles.
PMID- 26433802
TI - Effects of LI-4 and SP-6 Acupuncture on Labor Pain, Cortisol Level and Duration
of Labor.
AB - Nowadays, acupuncture is widely used to manage pain, and childbirth is a
condition requiring appropriate pain management interventions. The efficacy of
acupuncture in the management of labor pain has recently been studied, but the
results are not satisfactory and conflicts exist. In this study, we investigated
the effects of acupuncture on labor pain, serum cortisol level, and duration of
labor. We conducted a randomized, single-blind, controlled trial that included 63
nulliparous women: 32 in the study group and 31 in the control group. Acupuncture
was performed at the SP-6 and the LI-4 points in the study group, and sham
acupuncture was performed at the same points in the control group. Pain scores
and serum cortisol levels were measured before and after the intervention.
Changes in these measures and in the duration of labor were compared between the
groups. No significant variations in pain scores or serum cortisol levels were
observed between the two control groups. However, the duration of labor was
significantly lower (p < 0.001) in the group receiving real acupuncture. Our
results show that acupuncture is significantly associated with a decreased
duration of labor, even though it was no better than a placebo for the treatment
of labor pain.
PMID- 26433803
TI - Acupuncture Treatment of Chronic Low Back Pain by Using the Jingjin (Meridian
Sinews) Model.
AB - This case report details the unexpected and sustained relief from chronic low
back pain in a patient after a single acupuncture treatment. The treatment
administered on that occasion was based on the jingjin (i.e., "meridian sinew")
model of traditional acupuncture. Treatments based on the jingjin model involve
needling the ah shi (i.e., locally tender) points in myofascial tissue along the
jingjin pathway. Tight chains can be needled to treat symptoms that are either
close to or at some distance from the site of the needling treatment. In this
patient, the points were in the gastrocnemius muscle and the hamstring muscles,
which are part of the Bladder jingjin pathway. The patient, a 69-year-old woman,
had had back pain for more than 40 years. The relief from the pain occurred
within a day after the treatment and, at the time of this report, the relief has
persisted for 5 months. This report examines two possible mechanisms for such a
result: (1) a local increase in the extensibility of the hamstrings could be
responsible or (2) the complex interactions within the central nervous system
that are involved in acupuncture treatment could be more important factors.
PMID- 26433804
TI - Acupuncture Treatment of Pain along the Gall Bladder Meridian in 15 Horses.
AB - This study reports on clinically significant relief of pain along the gall
bladder meridian in 15 sport horses. Both local and distant points were needled
in this study. Pain relief was marked not only locally but also in remote areas
along the gall bladder meridian. Clinical improvement was observed in all 15
horses within 30 seconds to 2 minutes after the treatment had started. Twelve
horses and three horses were rated as "cured" and "improved", respectively, when
they were re-examined 1-8 days after the treatment. The relief of somatic pain
was often associated with improved riding performance of the horses. These data
are relevant in terms of equine clinical pain relief, as well as in terms of
meridian therapy and the scientific theory of acupuncture.
PMID- 26433805
TI - Narrative Review of Perioperative Acupuncture for Clinicians.
AB - Acupuncture is one of the oldest forms of the natural healing arts. The exact
mechanisms of action are unknown at this time; however, current theories to
explain the benefits experienced after acupuncture include Traditional Chinese
Medicine and Western medicine concepts. Acupuncture may improve the quality of
perioperative care and reduce associated complications. Perioperative acupuncture
is apparently effective in reducing preoperative anxiety, postoperative nausea
and vomiting, and postoperative pain. The Pericardium-6 (P-6; Nei Guan), Yintang
(Extra 1), and Shenmen acupuncture points are the most studied and effective
acupuncture points in reducing preoperative anxiety, postoperative nausea and
vomiting, and postoperative pain experiences. Intraoperatively administered
acupuncture may reduce immunosuppression in patients and lessen intraoperative
anesthetic requirements, although the clinical usefulness of acupuncture in the
intraoperative period remains inconclusive. Perioperative acupuncture is a
promising intervention, but additional studies are needed to further understand
and define acupuncture's role throughout the perioperative period and determine
its clinical usefulness. The purpose of this article is to provide a brief
clinical review concerning acupuncture and its application for common issues that
occur in the perioperative period.
PMID- 26433806
TI - Acupuncture for Pain Management in Evidence-based Medicine.
AB - Pain is an enormous and prevalent problem that troubles people of all ages
worldwide. The effectiveness of acupuncture for pain management has been strongly
verified by large randomized controlled trials (RCTs) and meta-analyses.
Increasing numbers of patients with pain have accepted acupuncture treatment
worldwide. However, some challenges exist in establishing evidence for the
efficacy of acupuncture. A more applicable and innovative research methodology
that can reflect the effect of acupuncture in the settings of daily clinical
practice needs to be developed.
PMID- 26433807
TI - The International Federation of Gynecology and Obstetrics (FIGO) Initiative on
gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and
care.
PMID- 26433808
TI - Factors Affecting Distribution of Estrogenicity in the Influents, Effluents, and
Biosolids of Canadian Wastewater Treatment Plants.
AB - Canadian wastewater treatment plants (WWTPs) release significant amounts of
estrogenic chemicals to nearby surface waters. Environmental estrogens have been
implicated as the causative agents of many developmental and reproductive
problems in animals, including fish. The goals of this study were to assess the
estrogenic activity in the influents, effluents, and biosolids of thirteen
Canadian WWTPs using the yeast estrogen screen (YES) bioassay and to investigate
whether factors, such as wastewater treatment method, sample storage, extraction
efficiency, population, and summer/winter temperature had any effects on the
distribution of estrogenicity in the WWTPs. Results of the study showed that
estrogenicity from the influent to the effluent decreased in seven WWTPs,
increased in two WWTPs, and did not change in four WWTPs during the winter.
Estrogenic concentrations generally decreased in the order of biosolids >
influents > effluents and ranged from 1.57 to 24.6, 1.25E-02 to 3.84E-01, and
9.46E-03 to 3.90E-01 ng estradiol equivalents/g or ml, respectively. The
estrogenicity in the final effluents, but not those in the influents and
biosolids, was significantly higher in the summer than the winter. Among the WWTP
treatment methods, advanced, biological nutrient removal appeared to be the most
effective method to remove estrogenic chemicals from wastewaters in Canada. Our
studies help to identify factors or mechanisms that affect the distribution of
estrogenicity in WWTPs, providing a better understanding on the discharges of
estrogenic chemicals from WWTPs.
PMID- 26433809
TI - Dust-Metal Sources in an Urbanized Arid Zone: Implications for Health-Risk
Assessments.
AB - The available information concerning metal pollution in different dust sources
and the health effects in children remains limited in Mexico. This study focuses
on Hermosillo, which is an urbanized area located in the Sonoran Desert in which
soil resuspension and dust emission processes are common. The metal content of
arsenic (As), chromium (Cr), manganese (Mn), and lead (Pb) were determined in
three dust sources (playgrounds, roofs, and roads), each representing different
exposure media (EM) for these elements. The metal levels in dust were found in
the order of Mn > Cr > Pb > As with the highest metal content found in road dust.
Despite the similar average metal distributions, principal component analysis
shows a clear separation of the three EM with playground dust related to Cr and
Mn and road dust to As and Pb. However, the geoaccumulation index results
indicate that dust samples are uncontaminated to moderately polluted, except for
Pb in road dust, which is considerably high. In addition, the enrichment factor
suggests an anthropogenic origin for all of the studied metals except for Mn. In
this context, the hazard index (HI) for noncarcinogenic risk is >1 in this
population and thus represents a potential health risk. The spatial distribution
for each metal on EM and the HI related to the marginality index could represent
a more accurate decision-making tool in risk assessment studies.
PMID- 26433810
TI - Surgeon-performed bedside ultrasound to assess volume status: a feasibility
study.
AB - PURPOSE: Rapid assessment of volume status in children is often difficult. The
purpose of this study was to evaluate the feasibility of surgeon-performed
ultrasound to assess volume status in patients with hypertrophic pyloric
stenosis. METHODS: Ultrasounds were performed on admission and before operation.
The diameters of the inferior vena cava (IVC) and aorta (Ao) were measured and
IVC/Ao ratios were calculated. Electrolytes were measured on admission and
repeated if warranted. Logistic regression was used to associate the clinical
outcome, defined as CO2 <=30 mEq/L, with IVC/Ao ratios. Predictive capacity was
estimated from the logistic regression for IVC/Ao ratios. Linear regression was
used to estimate associations between CO2 values and IVC/Ao ratios. RESULTS:
Thirty-one patients were enrolled. The IVC/Ao ratio is highly associated with
actual CO2 values (P < 0.001) and the clinical outcome (P = 0.004). For every
0.05 unit increase in IVC/Ao ratio, predicted CO2 decreased 1.1 units. For every
0.05 unit increase in the IVC/Ao ratio, the odds of having a CO2 <=30 mEq/L
increased 48% [OR = 1.48, 95% CI (1.13,1.94)]. Predictive capacity is maximized
at an IVC/Ao ratio of 0.75 as 83.9 % of subjects were correctly classified and
specificity and PPV = 100%. CONCLUSIONS: Surgeon-performed ultrasound to
determine IVC/Ao ratio is feasible. An IVC/Ao ratio of 0.75 predicted adequate
resuscitation.
PMID- 26433811
TI - Migrant workers in Sabah, East Malaysia: The importance of legislation and policy
to uphold equity on sexual and reproductive health and rights.
AB - Sabah, located in Southeast Asia, hosts the highest number of non-Malaysian
citizens (27.7%), predominantly the Indonesian and Filipino migrants in
comparison to other states in Malaysia. Sabah has inadequate data on migrants'
sexual and reproductive health and rights (SRHRs). Various migrant-related
policies and laws are present, but they do not offer full protection and rights
to legal migrants in terms of their SRHRs. The aim of the laws and policies
appears to be controlling the migrants from having any negative impact on the
locals, rather than protecting migrants' health and rights. This affected their
rights to marriage, having children, increase their vulnerabilities to labour
trafficking and sexual abuse and access to health-care services. Female migrant
workers and undocumented migrants form the most vulnerable subgroups of migrants.
This narrative review highlights the status of SRHRs of migrants in Sabah and the
migrant-related Malaysian laws and policies affecting their SRHRs.
PMID- 26433812
TI - Bands, Chords, Tendons, and Membranes in the Heart: An Imaging Overview.
AB - Crests, bands, chords, and membranes can be seen within the different cardiac
chambers, with variable clinical significance. They can be incidental or can have
clinical implications by causing hemodynamic disturbance. It is crucial to know
the morphology and orientation of normal structures, aberrant or accessory
muscles, and abnormal membranes to diagnose the hemodynamic disturbance
associated with them. Newer generation computed tomographic scanners and faster
magnetic resonance imaging sequences offer high spatial and temporal resolution
allowing for acquisition of high resolution images of the cardiac chambers
improving identification of small internal structures, such as papillary muscles,
muscular bands, chords, and membranes. They also help in identification of other
associated complications, malformations, and provide a road map for treatment. In
this article, we review cross-sectional cardiac imaging findings of normal
anatomical variants and distinctive imaging features of pathologic bands, chords,
or membranes, which may produce significant hemodynamic changes and clinical
symptomatology.
PMID- 26433813
TI - Is UK cancer care broken?
PMID- 26433814
TI - Adjuvant sorafenib for liver cancer: wrong stage, wrong dose.
PMID- 26433815
TI - PD-L1 expression as a potential predictive biomarker.
PMID- 26433816
TI - Dose-limiting toxicity and maximum tolerated dose: still fit for purpose?
PMID- 26433817
TI - Cannabis and cancer: reality or pipe dream?
PMID- 26433818
TI - Hello. I have cancer. How are you?
PMID- 26433820
TI - Discordance between the results and conclusions of ICON7 - Authors' reply.
PMID- 26433821
TI - Discordance between the results and conclusions of ICON7.
PMID- 26433822
TI - Evolving treatment options for melanoma brain metastases.
AB - Melanoma is a leading cause of lost productivity due to premature cancer
mortality. Melanoma frequently spreads to the brain and is associated with rapid
deterioration in quality and quantity of life. Until now, treatment options have
been restricted to surgery and radiotherapy, although neither modality has been
well studied in clinical trials. However, the new immune checkpoint inhibitors
and molecularly targeted agents that have been introduced for treatment of
metastatic melanoma are active against brain metastases and offer new
opportunities to improve disease outcomes. New challenges arise, including how to
integrate or sequence multiple treatment modalities, and current practice varies
widely. In this Review, we summarise evidence for the treatment of melanoma brain
metastases, and discuss the rationale and evidence for combination modalities,
highlighting areas for future research.
PMID- 26433819
TI - Comparison of dabrafenib and trametinib combination therapy with vemurafenib
monotherapy on health-related quality of life in patients with unresectable or
metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of
a phase 3, open-label, randomised trial.
AB - BACKGROUND: In the COMBI-v trial, patients with previously untreated BRAF
Val600Glu or Val600Lys mutant unresectable or metastatic melanoma who were
treated with the combination of dabrafenib and trametinib had significantly
longer overall and progression-free survival than those treated with vemurafenib
alone. Here, we present the effects of treatments on health-related quality of
life (HRQoL), an exploratory endpoint in the COMBI-v study. METHODS: COMBI-v was
an open-label, randomised phase 3 study in which 704 patients with metastatic
melanoma with a BRAF Val600 mutation were randomly assigned (1:1) by an
interactive voice response system to receive either a combination of dabrafenib
(150 mg twice-daily) and trametinib (2 mg once-daily) or vemurafenib monotherapy
(960 mg twice-daily) orally as first-line therapy. The primary endpoint was
overall survival. In this pre-specified exploratory analysis, we prospectively
assessed HRQoL in the intention-to-treat population with the European
Organisation for Research and Treatment of Cancer quality of life (EORTC QLQ
C30), EuroQoL-5D (EQ-5D), and Melanoma Subscale of the Functional Assessment of
Cancer Therapy-Melanoma (FACT-M), completed at baseline, during study treatment,
at disease progression, and after progression. We used a mixed-model, repeated
measures ANCOVA to assess differences in mean scores between groups with baseline
score as covariate; all p-values are descriptive. The COMBI-v trial is registered
with ClinicalTrials.gov, number NCT01597908, and is ongoing for the primary
endpoint, but is not recruiting patients. FINDINGS: From June 4, 2012, to Oct 7,
2013, 1645 patients at 193 centres worldwide were screened for eligibility, and
704 patients were randomly assigned to dabrafenib plus trametinib (n=352) or
vemurafenib (n=352). Questionnaire completion rates for both groups were high
(>95% at baseline, >80% at follow-up assessments, and >70% at disease
progression) with similar HRQoL and symptom scores reported at baseline in both
treatment groups for all questionnaires. Differences in mean scores between
treatment groups were significant and clinically meaningful in favour of the
combination compared with vemurafenib monotherapy for most domains across all
three questionnaires during study treatment and at disease progression, including
EORTC QLQ-C30 global health (7.92, 7.62, 6.86, 7.47, 5.16, 7.56, and 7.57 at
weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively; p<0.001 for
all assessments except p=0.005 at week 40), EORTC QLQ-C30 pain (-13.20, -8.05,
8.82, -12.69, -12.46, -11.41, and -10.57 at weeks 8, 16, 24, 32, 40, 48, and
disease progression, respectively; all p<0.001), EQ-5D thermometer scores (7.96,
8.05, 6.83, 11.53, 7.41, 9.08, and 10.51 at weeks 8, 16, 24, 32, 40, 48, and
disease progression, respectively; p<0.001 for all assessments except p=0.006 at
week 32), and FACT-M Melanoma Subscale score (3.62, 2.93, 2.45, 3.39, 2.85, 3.00,
and 3.68 at weeks 8, 16, 24, 32, 40, 48, and disease progression, respectively;
all p<0.001). INTERPRETATION: From the patient's perspective, which integrates
not only survival advantage but also disease-associated and adverse-event
associated symptoms, treatment with the combination of a BRAF inhibitor plus a
MEK inhibitor (dabrafenib plus trametinib) adds a clear benefit over monotherapy
with the BRAF inhibitor vemurafenib and supports the combination therapy as
standard of care in this population.
PMID- 26433823
TI - Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential
mechanisms of synergy.
AB - Checkpoint blockade immunotherapy has received mainstream attention as a result
of striking and durable clinical responses in some patients with metastatic
disease and a reasonable response rate in many tumour types. The activity of
checkpoint blockade immunotherapy is not restricted to melanoma or lung cancer,
and additional indications are expected in the future, with responses already
reported in renal cancer, bladder cancer, and Hodgkin's lymphoma among many
others. Additionally, the interactions between radiation and the immune system
have been investigated, with several studies describing the synergistic effects
on local and distant tumour control when radiation therapy is combined with
immunotherapy. Clinical enthusiasm for this approach is strengthened by the many
ongoing trials combining immunotherapy with definitive and palliative radiation.
Herein, we discuss the biological and mechanistic rationale behind combining
radiation with checkpoint blockade immunotherapy, with a focus on the preclinical
data supporting this potentially synergistic combination. We explore potential
hypotheses and important considerations for clinical trial designs. Finally, we
reintroduce the notion of radiosensitising immunotherapy, akin to
radiosensitising chemotherapy, as a potential definitive therapeutic modality.
PMID- 26433825
TI - Disease kinetics for decision-making in advanced melanoma: a call for scenario
driven strategy trials.
AB - In the past 5 years, the treatment of metastatic melanoma has changed from almost
no effective treatment to the use of targeted and immune therapies with proven
improvements in survival. The time has now come to define the optimal drug
combinations, sequence of treatment, and drug regimens (intermittent vs
continuous dosing) in the treatment of patients with metastatic melanoma. In view
of the prevalence of advanced melanoma, finite resources, and the heterogeneity
of disease characteristics, not all possibilities can be tested in therapeutic
trials starting from an unselected population of patients with metastatic
melanoma. In practice, clinicians rely on a few clinically derived signals,
especially dynamic signals, to categorise patients into scenarios, from fast
disease kinetics to slow disease kinetics, which drive clinicians' therapeutic
decision making. The realistic goals of therapy are different in each scenario.
We recommend that these scenarios are incorporated into clinical trials as either
patient inclusion criteria or stratification factors. This approach is not only
feasible but is also the only way to generate evidence for more effective and
individualised treatment strategies for patients with metastatic melanoma.
PMID- 26433824
TI - Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.
AB - The incidence of brain metastases has increased as a result of improved systemic
control and advances in imaging. However, development of novel therapeutics with
CNS activity has not advanced at the same rate. Research on molecular markers has
revealed many potential targets for antineoplastic agents, and a particularly
important aberration is translocation in the ALK gene, identified in non-small
cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK
rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in
CNS disease is limited by poor blood-brain barrier penetration and acquired drug
resistance. In this Review, we discuss potential pathways to target ALK
rearranged brain metastases, including next generation ALK inhibitors with
greater CNS penetration and mechanisms to overcome resistance. Other important
mechanisms to control CNS disease include targeting pathways downstream of ALK
phosphorylation, increasing the permeability of the blood-brain barrier,
modifying the tumour microenvironment, and adding concurrent radiotherapy.
PMID- 26433826
TI - Map-based cloning reveals the complex organization of the BnRf locus and leads to
the identification of BnRf(b), a male sterility gene, in Brassica napus.
AB - KEY MESSAGE: Sequencing of BAC clones reveals the complex organization of the
BnRf locus and allowed us to clone BnRf (b) , which encodes a nucleus-localized
chimeric protein BnaA7.mtHSP70-1-like. The male sterility in an extensively used
genic male sterility (GMS) line (9012A) in Brassica napus was regarded to be
conferred by BnMs3/Bnms3 and the multiallelic BnRf locus including three alleles.
We previously mapped BnRf to a 13.8 kb DNA fragment on the B. napus chromosome
A7. In the present study, we isolated bacterial artificial chromosome clones
individually covering the restorer allele BnRf (a) and the male-sterile allele
BnRf (b) , and revealed that the candidate regions of BnRf (a) and BnRf (b) show
complex structural variations relative to the maintainer allele BnRf (c). By
analyzing the recombination events and the newly developed markers, we delimited
BnRf (a) to a 35.9 kb DNA fragment that contained seven predicted open-reading
frames (ORFs). However, genetic transformation of the ORF G14 from both the male
sterile and restorer lines into wild-type Arabidopsis plants led to a stable male
sterile phenotype matching a 9012A-derived GMS line (RG206A); moreover, the male
sterility caused by G14 could be fully recovered by the restorer gene BnMs3.
These facts indicate that BnRf (b) corresponds to G14 while BnRf (a) likely
associates with another flanking ORF. G14 encodes a nucleus-localized chimeric
protein designated as BnaA7.mtHSP70-1-like. Ectopic expression of G14 in
Arabidopsis negatively regulates some vital genes responsible for tapetum
degeneration, and delayed programmed cell death of tapetum and led to the
developmental arrest of tetrads. Our work not only presents new insights on the
hereditary model of sterility control but also lays a solid foundation for
dissecting the molecular basis underlying male sterility and restoration in
9012A.
PMID- 26433827
TI - Fine mapping for double podding gene in chickpea.
AB - KEY MESSAGE: For the first time, fine mapping for sfl locus was carried out using
a battery of new STMS and SNP markers. The target region was delimited to 92.6 Kb
where seven annotated genes were found that could be candidate genes for the
simple/double podding trait in chickpea. Four recombinant inbred populations (RIP
1, RIP-7, RIP-11, and CPR-01) were used to map the double podding gene (sfl) in
chickpea. In RIP-1, the gene was initially mapped on linkage group (LG) 6 between
the two sequence-tagged microsatellite site (STMS) markers TA120 and TR1. Eight
new STMS markers were added onto LG6 in the target region and sfl locus was
finally located between CAGM27819 and CAGM27777 markers within an interval of 2
cM. Seven out of the eight markers were mapped in RIP-7 and its reciprocal RIP-11
confirming the location of the sfl locus to a 4.8 cM interval flanked by TR44 and
CAGM27705. Furthermore, using a high-density single nucleotide polymorphism (SNP)
map of CPR-01, sfl was mapped to the same genomic region in a 5.1 cM interval
between TR44 and the SNP scaffold1646p97220. Five pairs of near isogenic lines
(NILs) and eight recombinant inbred lines (RILs) were used to refine this region
in the chickpea physical map. Combining data from linkage analysis in four RIPs,
marker physical positions and recombination events obtained in both pairs of NILs
and selected RILs, sfl could be placed within a genomic window of 92.6 Kb. Seven
annotated genes were extracted from this region. The regulator of axillary
meristem-predicted gene could be a candidate gene for the simple/double podding
gene. This study provides additional set of markers flanking and tightly linked
to sfl locus that are useful for marker-assisted selection.
PMID- 26433828
TI - Complementary resistance genes in wheat selection 'Avocet R' confer resistance to
stripe rust.
AB - KEY MESSAGE: Complementary genes for resistance to wheat stripe rust in an Avocet
selection mapped to chromosome arms 3DL and 5BL. Susceptible Avocet selections
lacked the 5BL gene due to a chromosomal deletion. This study reports the
inheritance and genetic mapping of the YrA (temporary name of convenience to
describe the specificity) seedling resistance to wheat stripe rust (caused by
Puccinia striiformis f. sp. tritici; Pst) in a resistant selection of the
Australian cv. Avocet [Avocet R (AvR)-AUS 90660]. Genetic analysis was performed
on F2 populations and F3 generation families from crosses between wheats that
carried and lacked the YrA resistance. Greenhouse seedling tests with two
avirulent Pst pathotypes (104 E137 A- and 108 E141 A-) confirmed that the YrA
resistance was inherited as two complementary dominant genes. Ninety-two doubled
haploid (DH) lines from a cross between the Australian cv. Teal (Pst susceptible)
and AvR were used for DArT-Seq genotypic analysis to map the seedling resistance.
Marker-trait association analysis using 9035 DArT-Seq loci mapped the genes to
the long arms of chromosomes 3D (3DL) and 5B (5BL), respectively. F2 populations
from crosses between susceptible DH lines that carried either the 3DL or 5BL
marker genotypes confirmed the complementary gene model. Fluorescence in situ
hybridization (FISH) analysis determined that Teal carries a reciprocal T5B-7B
translocation. FISH analysis also identified a 5BL chromosomal deletion in Avocet
S relative to AvR that further validated the complementary gene model and
possibly explained the heterogeneity of closely related wheats carrying the YrA
resistance. The individual loci of the complementary YrA resistance were
designated Yr73 (3DL) and Yr74 (5BL). Candidate single gene reference stocks will
be permanently accessioned following cytological analysis to avoid the T5B-7B
translocation.
PMID- 26433830
TI - Editorial overview: Cell signalling and gene regulation-communication and control
as the twin pillars of systems biology.
PMID- 26433829
TI - A major quantitative trait locus conferring subgynoecy in cucumber.
AB - KEY MESSAGE: A major QTL conditioning high degree of femaleness in cucumber was
identified by marker analysis and next generation sequencing. Cucumber (Cucumis
sativus L.) is a model species for sex determination studies, and its yield is
associated with the degree of femaleness. Subgynoecy represents a sex form with a
high degree of femaleness for which the genetic basis remains elusive. In this
study, genetic analysis in the F2 and BC1 populations developed from a cross
between subgynoecious S-2-98 and monoecious M95 suggested a quantitative nature
of subgynoecy. Application of simple sequence repeat markers between
subgynoecious and monoecious bulks constructed from BC1 plants identified three
QTLs: sg3.1, sg6.1, and sg6.2. The major QTL sg3.1 contributed to 54.6% of the
phenotypic variation, and its presence was confirmed by genome-wide comparison of
SNP profiles between parental lines and a subgynoecious bulk constructed from BC6
plants. Using PCR-based markers developed from the SNP profile, sg3.1 was further
delimited to a genomic region of 799 kb. The genetic basis of subgynoecy revealed
here shall shed light on the development of elite cultivars with high yield
potential.
PMID- 26433831
TI - Crime and subjective well-being in the countries of the former Soviet Union.
AB - BACKGROUND: Criminal victimisation and subjective well-being have both been
linked to health outcomes, although as yet, comparatively little is known about
the relationship between these two phenomena. In this study we used data from
nine countries of the former Soviet Union (fSU) to examine the association
between different types of crime and subjective well-being. METHODS: Data were
obtained from 18,000 individuals aged 18 and above collected during the Health in
Times of Transition (HITT) survey in 2010/11 in Armenia, Azerbaijan, Belarus,
Georgia, Moldova, Kazakhstan, Kyrgyzstan, Russia and Ukraine. Information was
obtained on respondents' experience of crime (violence and theft) and self
reported affective (happiness) and cognitive (life satisfaction) well-being.
Ordered probit and ordinary least squares (OLS) regression analyses were
undertaken to examine the associations between these variables. RESULTS: In
pooled country analyses, experiencing violence was associated with significantly
lower happiness and life satisfaction. Theft victimisation was associated with
significantly reduced life satisfaction but not happiness. Among the individual
countries, there was a more pronounced association between violent victimisation
and reduced happiness in Kazakhstan and Moldova. CONCLUSIONS: The finding that
criminal victimisation is linked to lower levels of subjective well-being
highlights the importance of reducing crime in the fSU, and also of having
effective support services in place for victims of crime to reduce its
detrimental effects on health and well-being.
PMID- 26433832
TI - [Neuromuscular dynamic scapular winging: Clinical, electromyographic and magnetic
resonance imaging diagnosis].
AB - Dyskinesia of the scapula is a clinical diagnosis and includes all disorders
affecting scapula positioning and movement whatever its etiology. Scapular
winging is a subtype of scapular dyskinesia due to a dynamic prominence of the
medial border of the scapula (DSW) secondary to neuromuscular imbalance in the
scapulothoracic stabilizer muscles. The two most common causes of DSW are
microtraumatic or idiopathic lesions of the long thoracic nerve (that innerves
the serratus anterior) or the accessory nerve (that innerves the trapezius).
Diagnosis of DSW is clinical and electromyographic. Use of magnetic resonance
imaging (MRI) could be of interest to distinguish lesion secondary to a long
thoracic nerve from accessory nerve and to rule out scapular dyskinesia related
to other shoulder disorders. Causal neuromuscular lesion diagnosis in DSW is
challenging. Clinical examinations, combined with scapular MRI, could help to
their specific diagnosis, determining their stage, ruling out differential
diagnosis and thus give raise to more targeted treatment.
PMID- 26433833
TI - [Prevalence and impact of post-traumatic stress disorder in a disordered eating
population sample].
AB - OBJECTIVE: Eating disorders (ED) are associated with a higher prevalence of post
traumatic stress disorder (PTSD). However, the impact they may have on the
clinical features and severity of the ED remains unknown. In this study, we
assessed the prevalence and the impact of PTSD in a disordered eating population
sample. METHODS: We recruited patients with eating disorders during a period of 6
months, in 2014. The patients underwent a semistructured diagnostic interview by
trained psychiatrists. The severity of eating behaviours and PTSD was assessed
using the Eating Disorder Inventory 2 and the Impact of Event Scale - Revised.
RESULTS: One hundred and thirty patients (57 patients with anorexia nervosa, 26
with bulimia nervosa, 18 with eating disorder not otherwise specified and 29 with
binge eating disorder) were included. Our analyses revealed a PTSD rate of 33.9%
in patients with ED. No difference was observed between the ED subtypes. Severity
of ED was significantly higher among patients suffering from PTSD. Specific
clinical characteristics of the ED-PTSD association have been found. Analyses
revealed a significantly higher level of insecurity, interpersonal distrust,
impulsivity and a decrease of interoceptive awareness. DISCUSSION: The frequency
and negative impact of PTSD on ED reinforce the need for a systematic clinical
evaluation and the implementation of specific care.
PMID- 26433834
TI - Influenza prevention in nursing homes: Great significance of seasonal variability
and spatio-temporal pattern.
AB - OBJECTIVE: This work evaluated seasonal variations and spatio-temporal pattern of
respiratory tract infections (RTI) in geriatric nursing homes in order to improve
effective surveillance, prevention, control and management of RTI. METHODS:
Prospective surveillance of RTI (Low Respiratory Tract infections and Influenza
Like Illnesses) was conducted in 11 sites in Alsace over a 10-year period with
clinical case definitions and rapid tests (Immunoassay) to identify influenza
virus. RESULTS: Influenza national epidemic was a period at high risk of RTI in
nursing homes with variable impacts depending on the seasonal period. 2004-2005,
2008-2009, 2011-2012 and 2012-2013 were the periods with the highest impacts. The
higher risk was not well understood during these four influenza epidemics and
outbreaks occurred in numerous nursing homes despite the alerts and surveillance.
CONCLUSION: Information about seasonal variability and spatio-temporal patterns
of the RTI during the national epidemic periods is essential for the nursing
homes in order to help the health care workers and the visitors to understand the
risk for the residents and then to improve the implementation of the control and
prevention measures.
PMID- 26433835
TI - [Pseudotumoral thoracic splenosis in a patient with adult-onset Still disease and
reactive hemophagocytic syndrome].
PMID- 26433836
TI - Severe dizziness following rivaroxaban introduction in a parkinsonian patient:
Drug-drug interaction?
PMID- 26433837
TI - The influence of VKORC1 gene polymorphism on warfarin maintenance dosage in
pediatric patients: A systematic review and meta-analysis.
AB - INTRODUCTION: Warfarin is the most commonly used oral anticoagulant, however,
there are large interindividual variations in dose responses. Genetic
polymorphisms in CYP2C9, VKORC1 and CYP4F2 have been shown to play an important
role in variations in the warfarin maintenance dose in adults, but their effects
in children remain unclear. We aimed to investigate the effect of VKORC1
polymorphism on warfarin dosage in pediatric patients by meta-analysis. MATERIALS
AND METHODS: Using strict inclusion and exclusion criteria, we searched PubMed,
EMBASE, Cochrane library, Chinese Biomedical Literature Database, CNKI and
ChainInfo from 2004 to Mach 17th, 2015. The relationship between warfarin dose
and two single nucleotide polymorphisms of the VKORC1 gene (at positions -1639
and 1173) were analyzed using Revman version 5.2.3 software. RESULTS AND
CONCLUSIONS: Eight studies were included in the meta-analysis, involving 610
pediatric patients. Patients that were VKORC1 -1639 GA, AA or A carriers required
significantly lower warfarin dosage than GG carriers (the weighted mean
difference in warfarin dose ranged from -26% to -50%). Additionally, the age of
the patient and indication of warfarin (i.e. Fontan procedure) significantly
affected warfarin dosage, but changes in the target international normalized
ratio range had no effect. On the other hand, VKORC1 1173 polymorphisms showed no
significant effect on warfarin dosage, which differs from adult patients. In
conclusion, we found that VKORC1 -1639 gene polymorphisms have a moderate effect
on warfarin dosage in pediatric patients, but clinical characteristics such as
age and indication of warfarin also play an important role.
PMID- 26433838
TI - Primary hyperparathyroidism associated with a giant cell tumor: One case in the
distal radius.
AB - Hyperparathyroidism can present itself as brown tumors (or osteolytic expansive
lesions) that usually disappear after normalization of calcium and phosphate
levels. It rarely occurs simultaneously with a giant cell tumor. The authors
report one case of a localized form at the distal radius in a patient being
followed for primary hyperparathyroidism. The diagnostic challenges related to
the clinical and radiological similarities of these two pathological entities are
discussed, as they can lead to delays in therapeutic management.
PMID- 26433839
TI - Evaluation, Diagnosis, and Staging of Cutaneous Lymphoma.
AB - Primary cutaneous lymphomas (PCLs) are an extremely heterogeneous group of non
Hodgkin lymphomas that manifest in the skin. Their diagnosis is complex and based
on clinical lesion type and evaluation of findings on light microscopic
examination, immunohistochemistry and molecular analysis of representative skin
biopsies. The evaluation, classification, and staging system is unique for
mycosis fungoides (MF) and Sezary syndrome (SS), the most common subtypes of
cutaneous T-cell lymphoma (CTCL) versus the other subtypes of Non-MF/Non-SS CTCL
and the subtypes of cutaneous B-cell lymphoma (CBCL). Since current treatment is
stage-based, it is particularly important that the correct diagnosis and stage be
ascertained initially. The purpose of this article is to review the current
evaluation, diagnosis, classification, staging, assessment techniques, and
response criteria for the various types of both T-cell and B-cell PCLs.
PMID- 26433840
TI - Pathologic Diagnosis of Cutaneous Lymphomas.
AB - Primary cutaneous lymphomas comprise a prognostically heterogeneous group of
lymphocytic skin neoplasms, which display a broad spectrum of clinical,
histologic, immunophenotypic, and genetic features. The histopathological
examination plays an essential role and is often the starting point in the
diagnostic workup of cutaneous lymphomas. In most cases, the histopathological
and the phenotypic analysis alone are limited to provide a list of differential
diagnoses. As a consequence of overlapping clinical, histologic, phenotypic, and
genetic features among several entities of cutaneous lymphomas, the
clinicopathological correlation is of utmost importance to achieve the final
diagnosis.
PMID- 26433842
TI - Phototherapy of Mycosis Fungoides.
AB - Therapies based on ultraviolet light have long been established in mycosis
fungoides (MF). They have traditionally included whole-body ultraviolet light B,
both broad-band and narrow-band, and psoralen plus ultraviolet A. Phototherapy
may be applied alone in early stage MF or in combination with systemic therapy in
refractory early stage MF and advanced MF. This article reviews the most
frequently used forms of phototherapy for MF with emphasis on efficacy, safety,
and practical considerations.
PMID- 26433841
TI - Skin-Directed Therapies in Cutaneous T-Cell Lymphoma.
AB - Early stage mycosis fungoides represents the most common clinical presentation of
cutaneous lymphoma, with skin-directed therapies long established in its
treatment. These therapies continue to change as new treatment regimens emerge.
Other skin-directed treatments include light and radiation therapy. Therapies
with higher levels of evidence and less systemic toxicity are usually preferred
as first-line treatment. However, even these established therapies, like topical
corticosteroids and carmustine, lack randomized clinical trials to establish
their efficacy. Research is also needed to further define the role of combination
topical therapies and how skin-directed therapies can be used as adjuvants to
systemic medications.
PMID- 26433843
TI - Radiation Therapy for Cutaneous T-Cell Lymphomas.
AB - Radiation therapy is an extraordinarily effective skin-directed therapy for
cutaneous T-cell lymphomas. Lymphocytes are extremely sensitive to radiation and
a complete response is generally achieved even with low doses. Radiation therapy
has several important roles in the management of mycosis fungoides. For the rare
patient with unilesional disease, radiation therapy alone is potentially
curative. For patients with more advanced cutaneous disease, radiation therapy to
local lesions or to the entire skin can effectively palliate symptomatic disease
and provide local disease control. Compared with other skin-directed therapies,
radiation therapy is particularly advantageous because it can effectively
penetrate and treat thicker plaques and tumors.
PMID- 26433844
TI - The Role of Systemic Retinoids in the Treatment of Cutaneous T-Cell Lymphoma.
AB - Retinoids are natural and synthetic vitamin A analogs with effects on cell
proliferation, differentiation, and apoptosis. They have significant activity in
hematologic malignancies and have been studied extensively in cutaneous T-cell
lymphoma. Retinoids bind to nuclear receptors and exert their effects through
moderation of gene expression. Retinoic acid receptor and retinoic X receptor
exert regulatory activity in vivo, binding to distinct ligands. Studies
investigating systemic retinoids as monotherapy and in combination with other
agents active against cutaneous lymphoma are reviewed. Side effects associated
with retinoids include teratogenicity, dyslipidemias, and hypothyroidism, which
should be carefully monitored in patients receiving treatment.
PMID- 26433845
TI - The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma.
AB - Interferons are polypeptides that naturally occur in the human body as a part of
the innate immune response. By harnessing these immunomodulatory functions,
synthetic interferons have shown efficacy in combating various diseases including
cutaneous T-cell lymphoma. This article closely examines the qualities of
interferon alfa and interferon gamma and the evidence behind their use in the 2
most common types of cutaneous T-cell lymphomas, namely, mycosis fungoides and
Sezary syndrome.
PMID- 26433847
TI - Histone Deacetylase Inhibitors for Cutaneous T-Cell Lymphoma.
AB - Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin's T-cell lymphomas that
present as skin lesions. Mycosis fungoides with large cell transformation has a 5
year overall survival of 32% with involved skin and 7% with extracutaneous
involvement. Failure to cure advanced MF with large cell transformation and
peripheral T-cell lymphoma has resulted in a search for novel targeted agents
including antibodies and gene modulators. Histone deacetylase inhibitors are
small molecules that seem to be particularly active for T-cell lymphoma.
PMID- 26433846
TI - Methotrexate and Pralatrexate.
AB - This article reviews methotrexate and the more potent, related compound,
pralatrexate, for the treatment of cutaneous T-cell lymphomas, including mycosis
fungoides, Sezary syndrome, and CD30+ lymphoproliferative disorders. Although
these folate antagonists are traditionally viewed as antiproliferative cell cycle
inhibitors, it is recognized that they inhibit DNA methylation, providing a
rationale for their use as epigenetic regulators and cell proliferation
inhibitors. The underlying mechanisms are outlined, key supporting data
presented, followed by brief mention of recent mathematical modeling supporting
the general superiority of combination therapy. Several novel examples involving
folate antagonists are proposed.
PMID- 26433848
TI - Extracorporeal Photopheresis in the Treatment of Mycosis Fungoides and Sezary
Syndrome.
AB - Extracorporeal photopheresis (ECP) is an immunomodulating procedure that leads to
an expansion of peripheral blood dendritic cell populations and an enhanced TH1
immune response in cutaneous T-cell lymphoma (CTCL). Because of its excellent
side effect profile and moderate efficacy, ECP is considered first-line therapy
for erythrodermic mycosis fungoides (MF) and Sezary syndrome. Patients with a
measurable but low blood tumor burden are most likely to respond to ECP, and the
addition of adjunctive immunostimulatory agents may also increase response rates.
There may be a role for ECP in the treatment of refractory early stage MF, but
data are limited.
PMID- 26433849
TI - Monoclonal Antibodies.
AB - Use of monoclonal antibodies (mAbs) has revolutionized cancer therapy. Approaches
targeting specific cellular targets on the malignant cells and in tumor
microenvironment have been proved to be successful in hematologic malignancies,
including cutaneous lymphomas. mAb-based therapy for cutaneous T-cell lymphoma
has demonstrated high response rates and a favorable toxicity profile in clinical
trials. Several antibodies and antibody-based conjugates are approved for use in
clinical practice, and many more are in ongoing and planned clinical trials. In
addition, these safe and effective drugs can be used as pillars for sequential
therapies in a rational stepwise manner.
PMID- 26433850
TI - Other Chemotherapeutic Agents in Cutaneous T-Cell Lymphoma.
AB - Traditional chemotherapies, interleukins, phosphorylase inhibitors, and
proteasome inhibitors are important therapies available to patients with
cutaneous T-cell lymphoma (CTCL). Traditional chemotherapies, both in combination
and as single agents, are commonly used in relapsed, refractory CTCLs that behave
in an aggressive manner. Interleukins, phosphorylase inhibitors, and proteasome
inhibitors are less commonly used but data support a role in patients with more
refractory disease.
PMID- 26433851
TI - Hematopoietic Stem Cell Transplant for Mycosis Fungoides and Sezary Syndrome.
AB - Mycosis fungoides (MF) and Sezary syndrome (SS) are common types of primary
cutaneous T-cell lymphoma. Early-stage MF has a favorable prognosis and responds
well to skin-directed regimens. Patients with advanced-stage MF, transformed MF,
and SS are treated with combined systemic and skin-directed therapies. However,
the disease is incurable with standard regimens, and frequent relapses are
common. Owing to the lack of improvement in overall survival with standard
regimens, hematopoietic stem cell transplant (HSCT) has been explored as a
potential curative option. This article reviews the role of HSCT in MF/SS and
discusses data regarding conditioning regimens, treatment-related complications,
and outcomes.
PMID- 26433853
TI - Diagnosis and Management of Cutaneous B-cell Lymphoma.
AB - The diagnosis of primary cutaneous B-cell lymphoma (CBCL) requires that the
search for a more widespread lymphoma has been negative. The clinical
presentation, outlook, and treatment options of the common types of CBCLs, with
emphasis on differences or similarities to their nodal counterparts, are
discussed. Treatment may range from observation to topical therapies to systemic
therapies, depending on the histology, degree and area of skin involvement,
patient performance, and comorbidities. Rare lymphomas, such as intravascular
large B-cell lymphoma and Epstein-Barr virus-positive cutaneous
lymphoproliferations that are associated with immunodeficiency, are also briefly
described.
PMID- 26433852
TI - Practical Management of CD30+ Lymphoproliferative Disorders.
AB - Primary cutaneous CD30+ lymphoproliferative disorders (LPDs) account for
approximately 25% of cutaneous lymphomas. Although these LPDs are clinically
heterogeneous, they can be indistinguishable histologically. Lymphomatoid
papulosis rarely requires systemic treatment; however, multifocal primary
cutaneous anaplastic large cell cutaneous lymphoma and large cell transformation
of mycosis fungoides are typically treated systemically. As CD30+ LPDs are rare,
there is little published evidence to support a specific treatment algorithm.
Most studies are case reports, small case series, or retrospective reviews. This
article discusses various treatment choices for each of the CD30+ disorders and
offers practical pearls to aid in choosing an appropriate regimen.
PMID- 26433854
TI - Cutaneous Lymphoma.
PMID- 26433856
TI - Dental Pulp Status of Posterior Teeth in Patients with Oral and Oropharyngeal
Cancer Treated with Concurrent Chemoradiotherapy.
AB - INTRODUCTION: The absence of tooth sensitivity has been observed in patients who
have undergone radiotherapy. The aim of this investigation was to evaluate the
effects of concurrent chemoradiotherapy on the pulp status of posterior teeth in
patients with malignant oral and oropharyngeal cancer. METHODS: Twenty-one
patients diagnosed with malignant oral and oropharyngeal cancer undergoing
concurrent chemoradiotherapy underwent cold thermal pulp sensitivity testing and
electric pulp testing of 4 teeth, 1 from each quadrant, at 4 points in time (PT):
before radiotherapy (PT1), after 30-35 Gy (PT2), at the end of radiotherapy at 66
70 Gy (PT3), and 4 months (PT4) after beginning radiotherapy. RESULTS: All 84
teeth tested positive to cold thermal pulp sensitivity testing at PT1 (100%) and
25 teeth at PT2. No tooth responded at PT3 and PT4 (100%). A statistically
significant difference (P < .05) existed in the number of positive responses
between different points in time. CONCLUSIONS: Radiotherapy decreased the number
of teeth responding to pulp sensitivity testing after doses greater than 30-35
Gy.
PMID- 26433855
TI - Effect of Intracanal Cryotherapy on Reducing Root Surface Temperature.
AB - INTRODUCTION: The positive effect of cryotherapy has been widely described in
medicine. The aim of the present study was to validate a new methodology to
reduce and maintain external root surface temperature for at least 4 minutes.
METHODS: Twenty extracted single-rooted teeth were instrumented to size 35/.06
and subjected to 2 different irrigation interventions with a repeated-measures
design using 5% sodium hypochlorite first (control) and 2.5 degrees C cold saline
solution later (experimental). In both, 20 mL of the irrigant solution was
delivered for a total time of 5 minutes with a microcannula attached to the
EndoVac system (Kerr Endo, Orange County, CA) inserted to the working length. The
initial and lowest temperatures were recorded in the apical 4 mm with a digital
thermometer for both irrigants. Data were analyzed with the repeated measure
analysis of variance (Greenhouse-Geisser correction) and Bonferroni post hoc
tests. Differences in maintaining a -10 degrees C temperature reduction over 4
minutes were assessed with the Fisher exact test. RESULTS: Although significant
differences were found between the initial and lowest temperatures in both the
control and experimental irrigation procedures (P < .001), the experimental
intervention reduced it almost 10 times that of the control. When maintaining a
10 degrees C temperature reduction over 4 minutes, the teeth in the experimental
group also sustained significantly better results (P = 3.047 * 10(-10)).
CONCLUSIONS: Using cold saline solution as the final irrigant reduced the
external root surface temperature more than 10 degrees C and maintained it for 4
minutes, which may be enough to produce a local anti-inflammatory effect in the
periradicular tissues.
PMID- 26433858
TI - Requiring On-Site Evaluation in the Nursing Home Before Hospital Transfer: Is
This Proposed CMS Rule Change Feasible and Safe?
PMID- 26433857
TI - Micro-Computed Tomographic Evaluation of the Influence of Root Canal System
Landmarks on Access Outline Forms and Canal Curvatures in Mandibular Molars.
AB - INTRODUCTION: This study investigated the influence of anatomic root canal system
landmarks on access outline forms of mandibular molars and correlated these to
the theoretical distance of orifice relocation and changes in canal primary
curvature. METHODS: Thirty relatively calcified human mandibular molars were
selected and examined by micro-computed tomographic imaging. Three-dimensional
volume reconstructions were made, root canal system landmarks identified, and
plotted: canal orifices, canal position at the furcation level, and pulp horn
location. Each landmark was separately projected onto the occlusal surface, and 3
access designs were respectively proposed: (1) minimally invasive, (2) straight
line furcation, and (3) straight-line radicular. For each access design, the
theoretical distance of orifice relocation and canal primary curvature were
determined. Data were submitted to 2-way repeated measures analysis of variance
(alpha < 0.05). RESULTS: The orifice relocation distance required to obtain each
type of access outline was greater for radicular-based accesses (0.97 +/- 0.32
mm) than for furcation accesses (0.52 +/- 0.30 mm, P < .001) and resulted in a
greater change in canal primary curvature (P < .001; 15.9 degrees +/- 4.6
degrees and 9.4 degrees +/- 4.3 degrees , respectively). The canal primary
curvature for each access outline type was statistically different from each
other (P < .0001), whereas the minimally invasive access showed the highest mean
angle (40.1 degrees +/- 8.4 degrees ) followed by the straight-line furcation
(30.7 degrees +/- 7.5 degrees ) and the straight-line radicular accesses (24.2
degrees +/- 8.4 degrees ). CONCLUSIONS: The use of different landmarks to
establish access outline designs affected the primary angle of curvature in
relatively calcified mandibular molars.
PMID- 26433860
TI - Rapid Geriatric Assessment.
PMID- 26433861
TI - How Should Cognitive Impairment Be Recognized?
PMID- 26433862
TI - Hospitalization and Mortality Rates in Long-Term Care Facilities: Does For-Profit
Status Matter?
AB - OBJECTIVES: To establish if proprietary status (ie, for-profit or not-for-profit)
is associated with mortality and hospitalizations among publicly funded long-term
care (nursing) homes. METHODS: We conducted a retrospective cohort study of new
admissions in 640 publicly funded long-term care facilities in Ontario, Canada
(384 for-profit, 256 not-for-profit). A population-based cohort of 53,739
incident admissions into long-term care facilities between January 1, 2010, and
March 1, 2012, was observed. We measured adjusted rates of hospital admissions
and mortality, per 1000 person-years (PY) of follow-up, among for-profit and not
for-profit facilities at 3, 6, and 12 months postadmission. Rates were measured
postadmission and until discharge or death, whichever came first. RESULTS: One
year after admission and before discharge, 11.7% of residents died and 25.7% had
at least one hospitalization. After 12 months of follow-up, residents in for
profit facilities had a hospitalization rate of 462 per 1000 PY versus 358 per
1000 PY in not-for-profit facilities. During this period, the crude mortality
rate in for-profit facilities was 208 per 1000 PY versus 185 per 1000 PY in not
for-profit facilities. At 3, 6, and 1 year after admission, for-profit facilities
had an adjusted hazard ratio of 1.36 (95% confidence interval [CI] 1.28-1.43),
1.33 (95% CI 1.27-1.39), and 1.25 (95% CI 1.21-1.30) for hospitalizations and
hazards of 1.20 (95% CI 1.11-1.29), 1.16 (95% CI 1.09-1.24), and 1.10 (95% CI
1.05-1.16) for mortality, respectively. CONCLUSIONS: Publicly funded for-profit
facilities have significantly higher rates of both mortality and hospital
admissions.
PMID- 26433863
TI - Reply to the Letter to Editor by Maeda et al.
PMID- 26433864
TI - Intensity and Types of Physical Exercise in Relation to Dementia Risk Reduction
in Community-Living Older Adults.
AB - OBJECTIVE: To systematically examine the amount and type of physical exercise
that might reduce the future risk of dementia in community-living older people.
DESIGN: Six-year observational study. SETTING: All the Elderly Health Centers
(EHCs) of the Department of Health in Hong Kong. PARTICIPANTS: A total of 15,589
community-living Chinese aged 65 years and older with no history of stroke,
clinical dementia, or Parkinson disease when they completed health assessment at
the EHCs in the first 6 months of 2005. MEASUREMENTS: Self-reported habitual
physical exercise patterns, including the frequency, duration, and type of
exercise, at baseline and Year 3 were analyzed. The study outcome was incident
dementia in 6 years. Dementia was defined by presence of clinical dementia in
accordance with the 10th revision of the International Statistical Classification
of Diseases and Related Health Problems or Clinical Dementia Rating of 1 to 3.
RESULTS: Both the cognitively stable and incident groups reported exercising a
median of 7 days per week and 45 minutes per day at baseline and Year 3. The
former practiced aerobic and mind-body exercises more at baseline and Year 3,
whereas the latter practiced stretching and toning exercises more. The odds ratio
for dementia remained significant for aerobic (0.81; 95% confidence interval 0.68
0.95; P = .01) and mind-body exercises (0.76; 0.63-0.92; P = .004) after
excluding participants who developed dementia within 3 years after baseline and
adjusting for important potential confounders, such as age, gender, educational
level, and physical and psychiatric comorbidities. CONCLUSION: Although physical
exercise is widely promoted as a nonpharmacological intervention for dementia
prevention, not all types of exercise appear to be useful in reducing risk of
dementia in older people. Our findings suggest that daily participation in
aerobic and mind-body but not stretching and toning exercises might protect
community-living older adults from developing dementia.
PMID- 26433865
TI - Is Aging in Place Delaying Nursing Home Admission?
AB - OBJECTIVES: This study examines whether aging in place (community-based living
before admission to a nursing home) delays nursing home admission among New York
State home health care recipients. DESIGN: Retrospective cohort study (January
2007-December 2012). SETTING: New York State. PARTICIPANTS: Adults age 65+ who
received home health services for at least 2 months before permanent nursing home
admission. MEASUREMENT AND ANALYSIS: Permanent transition is defined as home care
patients who are discharged to and stay at a nursing home for more than 3 months.
Data were abstracted from the Minimum Data Set (MDS) and Outcome and Assessment
Information Set (OASIS). Descriptive and bivariate Kruskal-Wallis and chi(2)
tests were performed. RESULTS: The average age of nursing home residents at
admission remained steady at 83 years between 2007 and 2012. The proportion of
minority populations (Asian, black, Hispanic/Latino) increased, whereas the white
population declined (P < .0001). The average length of stay at home increased 8
months, from 17 months in 2007 to 25 months in 2012 (P < .0001). Chronic
conditions with significant increases in prevalence during the study period were
hypertension (P < .0009), dementia (P < .0001), heart failure (P = .05), urinary
incontinence (P < .0001), and bowel incontinence (P < .0001). Increases in
functional disabilities requiring extensive human assistance included toileting,
dressing, personal hygiene, and transferring (all P < .001). CONCLUSION: Home
health services enabled recipients to remain at home 8 months longer, thus
delaying nursing home entry. Given the increase in prevalence of comorbidities
and disability, we anticipate a concomitant increase in support services at the
nursing home. These results may inform policy and staffing decisions regarding
adjustments in required caregivers' credentials and nurse-patient ratios.
PMID- 26433866
TI - Pain management in pigs undergoing experimental surgery; a literature review
(2012-4).
AB - Failure to provide effective analgesia to animals in noxious studies contravenes
the obligation to refine animal experimentation and, by increasing 'noise' in
physiological data sets, may decrease the scientific validity of results. Pig
models of surgical conditions are becoming increasingly important and used for
translational work. This review aimed to determine the extent to which the recent
biomedical literature describes pain assessment and alleviation in pigs
recovering from experimental surgery. Three databases (Medline, Web of Knowledge,
and Google Scholar) were searched to find relevant studies published from January
2012 to March 2014. Information on pain assessment and peri- and postoperative
analgesia was extracted. The review identified 233 papers meeting selection
criteria. Most articles (193/233, 83%) described use of drugs with analgesic
properties, but only 87/233 (37%) described postoperative analgesia. No article
provided justification for the analgesic chosen, despite the lack of guidelines
for analgesia in porcine surgical models and the lack of formal studies on this
subject. Postoperative pain assessment was reported in only 23/233 (10%)
articles. It was found that the reporting of postoperative pain management in the
studies was remarkably low, reflecting either under-reporting or under-use.
Analgesic description, when given, was frequently too limited to enable
reproducibility. Development of a pain-scoring system in pigs, together with the
mandatory description of pain management in submitted articles, would contribute
to improved laboratory pig welfare.
PMID- 26433867
TI - ABO (histo) blood group phenotype development and human reproduction as they
relate to ancestral IgM formation: A hypothesis.
AB - The formation of a histo (blood) group) ABO phenotype and the exclusion of an
autoreactive IgM or isoagglutinin activity arise apparently in identical
glycosylation of complementary domains on cell surfaces and plasma proteins. The
fundamental O-glycan emptiness of the circulating IgM, which during the neonatal
amino acid sequencing of the variable regions is exerting germline-specific O
GalNAc glycan-reactive serine/threonine residues that in the plasma of the adult
human blood group O individuals apparently remain associated with the open
glycosidic sites on the ABOH convertible red cell surface, must raise suggestions
on a transient expression of developmental glycans, which have been "lost" over
the course of maturation. In fact, while the mammalian non-somatic, embryogenic
stem cell (ESC)- germ cell (GC) transformation is characterized by a transient
and genetically as-yet-undefined trans-species-functional O-GalNAc glycan
expression, in the C57BL/10 mouse such expression was potentially identified in
growth-dependent, blood group A-like GalNAc glycan-bearing, ovarian glycolipids
complementary with the syngeneic anti-A reactive IgM, which does not appear in
early ovariectomized animals. This non-somatically encoded, polyreactive,
ancestral IgM molecule has not undergone clonal selection and does primarily not
differentiate between self and non-self and might, due to amino acid hydroxyl
groups, highly suggest substrate competition with subsequent O-glycosylations in
ongoing ESC-GC transformations and affecting GC maturation. However, the membrane
bound somatic N/O-glycotransferases, which initiate, after formation of the
zygote, the complex construction of the human ABO phenotypes in the trans
cisternae of the Golgi apparatus, are associated and/or completed with soluble
enzyme versions exerting identical specificities in plasma and likely competing
vice versa by glycosylation of neonatal IgM amino acids, where they suggest to
accomplish the clearance of anti-A autoreactivity at germline serine and
threonine residues. Sustaining the lineage-maintaining position of the classic A
allele and the discovery of the OA hybrid alleles at the normal ABO locus and in
heterozygous ESC lines have, together with clinical observations, raised
discussions about a silent A-allelic support within blood group O reproduction.
However, the question of whether a fictional "continued blood group O inbreeding"
ultimately occurs without the A-allelic or somatic function remains unanswered
because the genetic relationship between non-somatic O-GalNAc-glycosylations that
operate before sperm-egg recognition and somatic O-GalNAc-glycosylations that
arise after the formation of the zygote remains to be elucidated.
PMID- 26433868
TI - Noduler an immune protein augments infection-induced cell proliferation through
cross-talking with p38 MAPK.
AB - Noduler, an immune protein that mediates nodule formation by binding to specific
bacteria and hemocytes was previously reported in the wild tasar silkworm,
Antheraea mylitta. However, the molecular mechanism underlying nodulation in
lepidopterans remains unclear. The present study is performed to investigate the
functional connection between Noduler with various signalling pathways. It was
observed that Noduler is an upstream factor in the phenoloxidase cascade and its
knockdown has no direct effect on Toll/Imd pathway inducible genes. Additionally,
Noduler was shown to stimulate cell proliferation via activation of p38 mitogen
activated protein kinase (MAPK). Inhibition of p38 in the infected hemocytes
cultured in vitro resulted in reduced cell proliferation and melanization. These
results suggest that Noduler mediates nodulation via p38/MAPK signalling. This is
the first report implicating the p38 MAPK signalling pathway in the nodulation
response of insects.
PMID- 26433869
TI - Lateral Sesamoid Position Relative to the Second Metatarsal in Feet With and
Without Hallux Valgus: A Prospective Study.
AB - We sought to determine whether hallux valgus displaces the sesamoid bones
laterally away from a stationary first metatarsal or whether the first metatarsal
head is displaced medially from the stationary sesamoids, which remain in
position relative to the rest of the forefoot. We reviewed weightbearing
radiographs in the dorsal plantar view of 128 consecutive patients (149 feet)
seen over 2 months in 2014. Of these, 82 feet (55%) had a hallux valgus angle of
>15 degrees (hallux valgus group) and 67 feet (45%) had an angle of no more than
15 degrees (control group). We measured the absolute distances from the center
of the lateral sesamoid and the first metatarsal head to the long axis of the
second metatarsal. Next, the relative distances, defined as the ratio of these 2
absolute distances to the length of the second metatarsal, were calculated to
adjust for foot size. Both the absolute and the relative distances from the
center of the first metatarsal head to the second metatarsal differed
significantly between the 2 groups and correlated positively with the hallux
valgus angle and first intermetatarsal angle. However, neither the absolute nor
the relative distance to the lateral sesamoid bone differed significantly between
the groups, nor did they correlate with either of the 2 angles. Thus, despite
medial shifting of the first metatarsal in hallux valgus, the lateral sesamoid
retains its relationship to the second metatarsal in transverse plane. Its
apparent lateral movement is a radiographic misinterpretation. Awareness of this
misinterpretation should improve the success of corrective surgery.
PMID- 26433870
TI - Effect of Preoperative Stress Radiographic Findings on Radiographic and Clinical
Outcomes of the Modified Brostrom Procedure for Chronic Ankle Instability.
AB - The purpose of the present study is to evaluate whether findings of instability
on preoperative stress radiographs of patients with chronic ankle instability
affects the radiographic and clinical outcomes after a modified Brostrom
procedure. A total of 45 consecutive patients (45 ankles) who had undergone the
modified Brostrom procedure for unilateral ankle joint instability and were
followed up for >=2 years were selected. The patients were classified into 2
groups according to the results of the preoperative stress radiographs: 1 group
with positive findings (35 [77.8%] patients; stress-positive group) and 1 group
with negative findings (10 [22.2%] patients; stress-negative group). The
radiographic and clinical outcomes were compared between the 2 groups. The mean
preoperative talar tilt measured on the stress radiograph was 14.4 degrees +/-
4.2 degrees and 4.8 degrees +/- 2.6 degrees in the stress-positive and stress
negative groups, respectively, a statistically significant difference.
Postoperative talar tilt improved in both groups, with a mean final talar tilt of
5.4 degrees +/- 3.4 degrees in the stress-positive group (p < .001) and 3.0
degrees +/- 1.5 degrees in the stress-negative group (p = .038). The average
American Orthopaedic Foot and Ankle Society ankle-hindfoot score in the stress
positive and stress-negative groups improved from 65.1 +/- 14.6 to 90.0 +/- 6.3
(p < .001) and 72.5 +/- 9.3 to 92.6 +/- 7.8 (p = .007), respectively. The mean
postoperative satisfaction rate was 83.9 +/- 11.9 and 85.0 +/- 11.8 in the 2
groups. No statistically significant differences were seen in the preoperative
and postoperative American Orthopaedic Foot and Ankle Society ankle-hindfoot
scores or in postoperative satisfaction rates between the 2 groups.
PMID- 26433871
TI - Positron emission tomography to diagnose chronic Q fever.
PMID- 26433872
TI - Prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae
isolated from blood cultures in Africa.
AB - Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have been
isolated from many regions of the world. Epidemiological studies are being
conducted in Europe, North America, and Asia. No study has however been conducted
in Africa to determine the prevalence and distribution of ESBLs on the continent.
This literature review aimed at describing the prevalence of ESBL-producing
Enterobacteriaceae isolated from blood cultures, as well as the ESBL genes
involved at the international level. Our focus was mainly on Africa. We conducted
a literature review on PubMed. Articles related to our study field and published
between 1996 and 2014 were reviewed and entirely read for most of them, while we
only focused on the abstracts of some other articles. Relevant articles to our
study were then carefully reviewed and included in the review. The prevalence of
ESBL-producing Enterobacteriaceae differs from one country to another. The
results of our literature review however indicate that class A ESBLs prevail over
the other types. We took into consideration articles focusing on various types of
samples to assess the prevalence of ESBL-producing Enterobacteriaceae, but
information on isolates from blood cultures is limited. The worldwide prevalence
of ESBL-producing Enterobacteriaceae has increased over time. Evidence of ESBL
producing Enterobacteriaceae can be found in all regions of the world. Studies
conducted in Africa mainly focused on the Northern and Eastern parts of the
continent, while only rare studies were carried out in the rest of the continent.
PMID- 26433873
TI - An express sexual health service: in and out in a jiffy.
AB - Objectives The aims of the present study were to assess client satisfaction with
existing services, gauge the interest in an express service option and to compare
waiting times before and after the introduction of an express service. Methods A
survey evaluating satisfaction with existing services, waiting times and interest
in an express service was offered to all clients attending the Western Sydney
Sexual Health Centre in May 2013. A pilot of the express service ran from May to
December 2013, and a follow-up survey was conducted in December 2013. Results
There was a high level of interest in the express service. Median waiting times
and satisfaction with waiting times improved following introduction of the
express clinic. A high level of satisfaction was reported in those who had used
the express service. Conclusions The express service was well received by clients
and has the potential to improve client waiting times, increase clinic capacity
and improve the overall client journey through the clinic. What is known about
the topic? Express service options for testing for sexually transmitted
infections (STIs) are being introduced both in Australia and overseas. Express
services have been shown to increase clinic capacity and can create cost savings.
They appear to be acceptable to clients. What does this paper add? This paper
demonstrates that an express service option can be successfully introduced in an
at-risk multicultural population. What are the implications for practitioners?
The present study helps show that new models can be successfully introduced into
long-standing traditional service models. Such models can help improve
efficiency, clinic capacity and may produce cost savings. An express clinic is an
option for screening asymptomatic clients for STIs. Clients complete a self
collected history and take self-collected specimens, and clinician-collected
blood tests and throat swabs are advised accordingly.
PMID- 26433874
TI - Abdominal Wall Angiosarcoma in a Patient With Drug-Induced Immunosuppression
Following Renal Transplantation.
PMID- 26433875
TI - Factors associated with antenatal and delivery care in Sudan: analysis of the
2010 Sudan household survey.
AB - BACKGROUND: Every day, globally approximately a thousand women and girls
needlessly die as a result of complications during pregnancy, childbirth or the 6
weeks following delivery. The majority of maternal deaths are avoidable and could
be prevented with proven interventions to prevent or manage complications during
pregnancy and child birth. The aim of this study was to examine factors
associated with underutilization of maternal health services in Sudan. METHODS:
Data was obtained from the Sudan Household Health Survey 2010(SHHS). The SHHS
collected data from 5730 women, aged 15-49 years and who were pregnant in the
last 2 years preceding the survey. The selection of the respondents was through a
multi-stage cluster sampling technique. Interviews were conducted with
respondents to collect data about their demographic characteristics, reproductive
history, pregnancy and child delivery. Univariate analysis and logistic
regression were used to analyze the data. RESULTS: The factors associated with
receiving antenatal care were, higher educational level (odds ratio (OR) = 3.428,
95% CI 2.473-4.751 - p value 0.001), higher household wealth (OR 1.656, 95% CI:
1.484-1.855 - p value 0.001) and low parity (OR =1.214, 95% CI: 1.035-1.423 - p
value 0.017). The factors associated with institutional delivery were higher
educational level (OR = 1.929, 95% CI: 1.380-2.697 - p value 0.001), high
household wealth (OR = 2.293, 95% CI: 1.988-2.644 p value 0.001), urban residence
(OR = 1.364, 95% CI: 1.081-1.721 p value 0.009), low parity (OR = 2.222, 95% CI:
1/786-2.765 p value 0.001), receiving ANC (OR = 3.342, 95% CI: 2.306-4.844 p
value 0.001) and complications during pregnancy (OR = 1.606, 95% CI: 1.319-1.957
p value 0.001). CONCLUSIONS: The factors associated with both antenatal care use
and institutional delivery are similar and interventions to target these include
expanding female education and improving coverage and affordability of health
services.
PMID- 26433877
TI - The Generality of Interview-Informed Functional Analyses: Systematic Replications
in School and Home.
AB - Behavioral interventions preceded by a functional analysis have been proven
efficacious in treating severe problem behavior associated with autism. There is,
however, a lack of research showing socially validated outcomes when assessment
and treatment procedures are conducted by ecologically relevant individuals in
typical settings. In this study, interview-informed functional analyses and skill
based treatments (Hanley et al. in J Appl Behav Anal 47:16-36, 2014) were applied
by a teacher and home-based provider in the classroom and home of two children
with autism. The function-based treatments resulted in socially validated
reductions in severe problem behavior (self-injury, aggression, property
destruction). Furthermore, skills lacking in baseline-functional communication,
denial and delay tolerance, and compliance with adult instructions-occurred with
regularity following intervention. The generality and costs of the process are
discussed.
PMID- 26433876
TI - Phase II, Multicenter, Single-Arm, Feasibility Study of Eribulin Combined With
Capecitabine for Adjuvant Treatment in Estrogen Receptor-Positive, Early-Stage
Breast Cancer.
AB - BACKGROUND: The present phase II, open-label, multicenter study explored the
feasibility, safety, and tolerability of eribulin, a novel non-taxane microtubule
inhibitor, plus capecitabine as adjuvant therapy. PATIENTS AND METHODS:
Postmenopausal women with early-stage, human epidermal growth factor receptor 2
(HER2)-negative, estrogen-receptor (ER)-positive breast cancer received four 21
day cycles of treatment with eribulin mesylate (1.4 mg/m(2) intravenously on days
1 and 8 of each cycle) combined with capecitabine (900 mg/m(2) orally twice daily
on days 1-14 of each cycle [standard schedule] or 1500 mg orally twice daily
using a 7-days on/7-days off schedule [weekly schedule]). Feasibility was
determined by the relative dose intensity (RDI) of the combination using
prespecified criteria for 80% of patients achieving an RDI of >= 85%, with a
lower 95% confidence boundary > 70%. RESULTS: The mean RDI was 90.6%, and the
feasibility rate was 81.3% among women (n = 67, mean age, 61.3 years) receiving
the standard schedule and 95.6% and 100% among women (n = 10, mean age 62.3
years) receiving the weekly schedule. Dose reductions, missed doses, and
withdrawals due to adverse events (most commonly hand-foot syndrome) ascribed to
capecitabine led to a higher RDI (93.5% vs. 87.8%) and feasibility rate (82.8%
vs. 71.9%) for eribulin than for capecitabine using the standard dosing schedule.
The most common adverse events were alopecia and fatigue. CONCLUSION: Eribulin
plus capecitabine with standard or weekly dosing schedules is feasible in
patients with early-stage, HER2-negative, ER-positive breast cancer. Full-dose
eribulin (1.4 mg/m(2) on days 1 and 8) with capecitabine (1500 mg orally twice
daily, 7 days on/7 days off) is recommended as a regimen for further evaluation.
PMID- 26433878
TI - Evaluation of Classroom Active Engagement in Elementary Students with Autism
Spectrum Disorder.
AB - This study evaluated the classroom measure of active engagement (CMAE), an
observational tool designed to measure active engagement in students with autism
spectrum disorder (ASD). Participants included 196 students with ASD and their
educators (n = 126) who were video-recorded at the beginning of the school year.
Findings documented limited active engagement overall, with students spending
less than half of the observation well-regulated, productive, or independent and
infrequently directing eye gaze and communicating. Confirmatory factor analysis
indicated that the structure of the CMAE was represented by a 5-factor model.
These findings underscore the need for improved active engagement in students
with ASD and show promise for a tool to measure behaviors associated with
positive educational outcomes in students with ASD.
PMID- 26433879
TI - The role of mannose binding lectin on fever episodes in pediatric oncology
patients.
AB - Despite significant changes in pediatric oncological therapy, mortality is still
high, mainly due to infections. Complement system as an ancient immune defense
against microorganisms plays a significant role in surmounting infections,
therefore, deficiency of its components may have particular importance in
malignancies. The present paper assesses the effect of promoter (X/Y) and exon 1
(A/0) polymorphisms of the MBL2 gene altering mannose binding lectin (MBL) serum
level in pediatric oncological patients with febrile neutropenia. Furthermore,
frequency distribution of MBL2 alleles in children with malignancies and age
matched controls was analysed. Fifty-four oncohematological patients and 53
children who had undergone pediatric surgery were enrolled into this
retrospective study. No significant differences were found in the frequency of
MBL2 alleles between the hemato-oncologic and control group. The average duration
of fever episodes was significantly shorter (p = 0.035) in patients carrying
genotypes (AY/AY and AY/AX) that encode normal MBL level, compared to individuals
with genotypes associated with lower functional MBL level (AX/AX, AY/0, AX/0, or
0/0) (days, median (IQ range) 3.7(0-5.4) vs. 5.0(3.8-6.6), respectively). In
conclusion, our data suggest that MBL2 genotypes may influence the course of
febrile neutropenia in pediatric patients with malignancies, and may contribute
to clarification of the importance of MBL in infections.
PMID- 26433880
TI - Absence of KNSTRN Mutation, a Cutaneous Squamous Carcinoma-Specific Mutation, in
Other Solid Tumors and Leukemias.
PMID- 26433881
TI - Upper limb DVT after an optical urethrotomy in a patient with a permanent
pacemaker: a case for continuing anticoagulation during low-risk urological
surgery.
PMID- 26433883
TI - The safety and efficiency of onabotulinumtoxinA for the treatment of overactive
bladder: a systematic review and meta-analysis.
AB - PURPOSE: To assess the impact on safety and efficiency of onabotulinumtoxinA
(BOTOX1, Allergan, Inc.) treatment in patients with an overactive bladder.
MATERIALS AND METHODS: We searched the PubMed((r)), Embase((r)), and Cochrane
Library Databases to identify all randomized controlled trials comparing the
outcomes of onabotulinumtoxinA and placebo for overactive bladder. The outcomes
included reductions in overactive bladder symptoms or improvements in the
function of bladder and the side effects of two treatments. The Cochrane
Collaboration Review Manager software (RevMan 5.1.4) was used for statistical
analysis. RESULTS: The study inclusion criteria were met by eight randomized
controlled trials involving 1875 patients. The synthesized data from these
randomized controlled trials indicated that onabotulinumtoxinA was better than
placebo in decreasing most overactive bladder symptoms (p < 0.00001, p < 0.00001,
p < 0.00001, p < 0.00001, p = 0.0003) in the micturition, urgency, urinary
incontinence, urgency urinary incontinence (UUI), and nocturia per day change,
respectively; however, the maximum cystometric capacity change from the baseline
appeared not to be significantly different between two methods (p = 0.05). In
addition, the side effects in the onabotulinumtoxinA group were more serious than
the placebo group (p < 0.00001, p = 0.009, p = 0.07, p < 0.0001, p = 0.03 in the
UTI, bacteriuria, dysuria, urinary retention, residual urine volume,
respectively). CONCLUSIONS: Compared with the placebo, onabotulinumtoxinA had
significantly and clinically relevant reductions in overactive bladder symptoms,
but it also leaded to more side effects.
PMID- 26433882
TI - Role of Smad signaling in kidney disease.
AB - Smads are the key intermediates of canonical transforming growth factor-beta (TGF
beta) signaling. These intermediates are divided into three distinct subgroups
based on their role in TGF-beta family signal transduction: Receptor-regulated
Smads (R-Smads) 1, 2, 3, 5 and 8, common Smad4, and inhibitory Smads6 and 7. TGF
beta signaling through Smad pathway involves phosphorylation, ubiquitination,
sumoylation, acetylation, and protein-protein interactions with mitogen-activated
protein kinases, PI3K-Akt/PKB, and Wnt/GSK-3. Several studies have suggested that
upregulation or downregulation of TGF-beta/Smad signaling pathways may be a
pathogenic mechanism in the progression of chronic kidney disease. Smad2 and 3
are the two major downstream R-Smads in TGF-beta-mediated renal fibrosis, while
Smad7 also controls renal inflammation. In this review, we characterize the role
of Smads in kidney disease, describe the molecular mechanisms, and discuss the
potential of Smads as a therapeutic target in chronic kidney disease.
PMID- 26433884
TI - Comparison of immunosuppressive therapies for IgA nephropathy after
tonsillectomy: three-course versus one-course steroid pulse combined with
mizoribine.
AB - PURPOSE: It has been reported that steroid pulse therapy for IgA nephropathy
improves renal prognosis. However, because of the side effects, steroid dose must
be restricted to some cases. Treatment effects of steroid on cases already
presenting with reduced renal function are unknown. In this study, we performed
tonsillectomy in patients with IgA nephropathy and conducted a comparative study
about subsequent immunosuppressive therapy. METHODS: Subjects were patients
younger than 70 years of age diagnosed with IgA nephropathy by renal biopsy.
Treatment protocols were a single-course steroid pulse combined with mizoribine
during a period from August 2006 to June 2010 (Group A; n = 34) and a three
course steroid pulse during a period from July 2010 to March 2013 (Group B; n =
32). Primary end points were excretory amounts of proteinuria, disappearance of
proteinuria and hematuria, and exacerbation of renal function. RESULTS: In both
the groups, proteinuria decreased significantly 12 months after treatment, and no
significant difference in alleviation effects on proteinuria was found between
groups. eGFR increased significantly 12 months after treatment in Group A,
whereas it tended to decrease in Group B. As for the preservation effect on eGFR,
Group A showed significantly higher preservation of eGFR. Similar results were
shown in the patients whose eGFR at the start of the treatment was less than 60
mL/min/1.73 m(2). CONCLUSIONS: Single-course steroid pulse therapy combined with
mizoribine was considered to have a protective effect on the renal function in
IgA nephropathy, especially accompanying renal dysfunction.
PMID- 26433885
TI - Effect of bevacizumab, a vascular endothelial growth factor inhibitor, on a rat
model of peritoneal sclerosis.
AB - PURPOSE: Peritoneal fibrosis is almost uniform feature encountered in peritoneal
dialysis patients. The transition of epithelial cells to mesenchymal phenotype,
neovascularization, and consequently development of peritoneal fibrosis occur due
to the involvement of peritoneal membrane by various insults such as uremia
itself, peritonitis attacks, and exposure to bio-incompatible peritoneal dialysis
fluids. Bevacizumab is a monoclonal antihuman antibody developed against vascular
endothelial growth factor and can reduce fibrosis by preventing
neovascularization. There has been no study so far that demonstrates the effect
of bevacizumab on peritoneal fibrosis in a rat model. METHODS: A total of 41
female Wistar albino rats were divided into six groups. The control group (C)
received 0.9 % isotonic saline (2 ml/day) intraperitoneally (i.p) for 21 days.
Chlorhexidine group (CH) received 15 % ethyl alcohol and 0.1 % chlorhexidine
gluconate (CG) in saline (2 ml/day) i.p for 21 days. The resting group (R)
received CG 2 ml/day i.p for 21 days. The bevacizumab-1 group (B1) received CG 2
ml/day i.p for 21 days and bevacizumab 2.5 mg/kg i.p as a single dose on day 21.
The bevacizumab-2 group (B2) received CG 2 ml/day for 21 days and bevacizumab 2.5
mg/kg i.p on day 0 and day 21. The bevacizumab-3 group (B3) received bevacizumab
2.5 mg/kg i.p on day 0 and day 21. Peritoneal samples were taken from the left
anterior abdominal wall. The thickness, vascularization, and fibrosis scores in
the peritoneal samples were assessed using a light microscope. RESULTS: On
histopathological evaluations, peritoneum thicknesses, vascularization scores,
and fibrosis significantly decreased in bevacizumab groups B1 and B2. CONCLUSION:
Histopathologically, bevacizumab was proven to attenuate fibrotic process in
experimental peritoneal sclerosis model.
PMID- 26433886
TI - A neurophysiological study of large- and small-diameter nerve fibers in the hands
of hemodialysis patients.
AB - PURPOSE: Polyneuropathy in patients with advanced clinical kidney disease is a
very disabling condition. The aim of this study was to evaluate
neurophysiological abnormalities of large- and small-diameter nerve fibers in the
hands of hemodialysis patients. METHODS: A total of 38 hemodialysis patients and
38 healthy control subjects underwent a conventional electrophysiological
examination. The function of small nerve fibers was assessed using cutaneous
silent period (CSP) measurement. RESULTS: Slower median nerve motor conduction
velocities were recorded in patients with fistula (p < 0.0001) and without
fistula (p < 0.001). Sensory median and ulnar nerve conduction velocities were
slower in both patient groups compared with the control group (p = 0.001). Median
sensory nerve action potential amplitudes were lower in patients with fistulas (p
= 0.009) and without fistulas (p = 0.005) compared with the control group.
Significantly prolonged F-wave latencies of the median (p = 0.002) and ulnar
nerves (p = 0.023) in patients with fistulas hands were observed. In 12/38 (32 %)
patients, the onset latencies of CSPs were significantly delayed (p = 0.001).
There was an inverse correlation of beta2-microglobulin and decreased conduction
velocities of the median nerves, while Kt/V was associated with improved sensory
nerve conduction velocity of the median nerve. An inverse correlation between
motor velocity of both nerves and hemodialysis duration was observed in the
patient groups. CONCLUSIONS: The measurement of CSPs provides a useful method for
assessing small nerve fibers. The role of A-delta fibers is often overlooked.
PMID- 26433887
TI - The association of high sCD163/sTWEAK ratio with cardiovascular disease in
hemodialysis patients.
AB - PURPOSE: Cardiovascular disease (CVD) is the most common cause of death in
hemodialysis (HD) patients. Transmembrane proteins that circulate as soluble form
such as tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and
CD163 have been proposed in previous studies as CVD biomarkers in chronic kidney
disease patients. In HD patients, since studies are scarce, the role of these
proteins is not completely understood. We tested the hypothesis that sTWEAK,
sCD163 or sCD163/sTWEAK ratio could be associated with cardiovascular disease in
HD patients. METHODS: We recorded current clinical and biological data, and we
measured sTWEAK and sCD163 serum levels by ELISA in 70 hemodialysis patients.
Univariate analysis and multivariate (logistic regression) analysis were used to
identify the relation between sTWEAK, sCD163 and sCD163/sTWEAK ratio and CVD.
RESULTS: In univariate analysis, CVD in HD patients is associated with higher
sCD163/sTWEAK ratio (p = 0.04), sCD163 (p = 0.07), CRP (p = 0.04), age (p =
0.07), smoking (p = 0.09) and vascular calcifications (p = 0.10). In multivariate
analysis, only logarithm of sCD163/sTWEAK ratio (p = 0.04) and smoking (p = 0.03)
was significantly associated with CVD. The levels of these molecules and their
ratio were correlated with atherosclerosis risk factors: diabetes mellitus, high
fasting glucose, tricipital skinfold thickness and CRP as well as (for
sCD163/sTWEAK) intravenous iron therapy. CONCLUSIONS: Cardiovascular disease is
associated with increased sCD163/sTWEAK ratio. To our knowledge, this is the
first report about this relationship in HD patients.
PMID- 26433888
TI - Impact of Elicitation on Antioxidant and Potential Antihypertensive Properties of
Lentil Sprouts.
AB - The aim of this study was to investigate the application of elicitors (500 MUM
ascorbic acid, 50 MUM folic acid, 5 mM glutamic acid and 50 ppm chitosan in 5 mM
glutamic acid) during lentil germination up to 8 days as a strategy to increase
germination rate and to enhance the accumulation of gamma-aminobutyric acid
(GABA) and phenolic compounds. The effect of elicitation on the protein profile
and antioxidant and angiotensin I converting enzyme (ACE) inhibitory activities
of sprouted lentils was also evaluated. The application of elicitors did not
negatively affect the germination yield of lentils and no significant changes on
the protein pattern of lentils germinated in the presence of elicitors were
observed. Chitosan/glutamic acid increased by 1.6-fold the GABA content in lentil
sprouts, whilst ascorbic and folic acids as well as chitosan/glutamic acid were
highly effective to enhance the total content of phenolic compounds and the
antioxidant activity of sprouted lentils. All elicited lentil sprouts showed
ability to inhibit ACE activity (IC50: 9.5-11.9 MUg peptides/mL). Therefore,
elicitation can be considered a promising approach to improve the content of
compounds with antioxidant and potential antihypertensive activities in lentil
sprouts.
PMID- 26433889
TI - An Efficient and Practical Smart Card Based Anonymity Preserving User
Authentication Scheme for TMIS using Elliptic Curve Cryptography.
AB - In the last few years, numerous remote user authentication and session key
agreement schemes have been put forwarded for Telecare Medical Information
System, where the patient and medical server exchange medical information using
Internet. We have found that most of the schemes are not usable for practical
applications due to known security weaknesses. It is also worth to note that
unrestricted number of patients login to the single medical server across the
globe. Therefore, the computation and maintenance overhead would be high and the
server may fail to provide services. In this article, we have designed a medical
system architecture and a standard mutual authentication scheme for single
medical server, where the patient can securely exchange medical data with the
doctor(s) via trusted central medical server over any insecure network. We then
explored the security of the scheme with its resilience to attacks. Moreover, we
formally validated the proposed scheme through the simulation using Automated
Validation of Internet Security Schemes and Applications software whose outcomes
confirm that the scheme is protected against active and passive attacks. The
performance comparison demonstrated that the proposed scheme has lower
communication cost than the existing schemes in literature. In addition, the
computation cost of the proposed scheme is nearly equal to the exiting schemes.
The proposed scheme not only efficient in terms of different security attacks,
but it also provides an efficient login, mutual authentication, session key
agreement and verification and password update phases along with password
recovery.
PMID- 26433890
TI - Targets, Toxins, and T Cells--a Review of New Monoclonal Antibodies in the
Treatment of Peripheral T Cell Lymphomas.
AB - The peripheral T cell lymphomas (PTCLs) are a heterogeneous group of neoplasms
for which standardized treatment approaches remain elusive. A number of new
therapeutic agents have become available, of which monoclonal antibodies (MAbs)
represent a powerful tool for targeted treatment of PTCLs. Therapeutic MAbs vary
in their structure, targets, and mechanisms of action. Common mechanisms of
action include antibody-dependent cell-mediated cytotoxicity, complement
dependent cytotoxicity, direct apoptosis, blocking of receptors or signaling
pathways, delivery of cytotoxic agents to tumor cells, and binding to and
blocking biologically active molecules. This review will focus on recent
published evidence for the various MAbs used in the treatment of PTCLs. The
results overall have been very promising, and the future will see more trials
with these antibodies alone and in various therapy combinations, as well as newer
ones with novel modifications, conjugates, and targets.
PMID- 26433891
TI - Mature T-cell leukemias: Molecular and Clinical Aspects.
AB - Mature T-cell leukemias are a group of uncommon lymphoid neoplasms. These
disorders have widely variable clinical features, ranging from indolent, slowly
progressive processes to diseases with rapidly progressive courses, leading to
death. Cytogenetic aberrations have long been identified in some of these
diseases, and recent studies have found recurrent genetic mutations that
contribute to their pathogenesis. Conventional multiagent chemotherapy lacks
significant efficacy in this group of diseases and therapies vary from
immunosuppression to treatment with monoclonal antibodies, antiviral agents, and
hematopoietic stem cell transplantation. The recent expansion of knowledge
regarding the underlying genetic basis of these disorders raises hope that new,
more targeted therapeutic approaches will be available to patients in the near
future.
PMID- 26433892
TI - N-acetylcysteine stimulates protein synthesis in enterocytes independently of
glutathione synthesis.
AB - Dietary supplementation with N-acetylcysteine (NAC) has been reported to improve
intestinal health and treat gastrointestinal diseases. However, the underlying
mechanisms are not fully understood. According to previous reports, NAC was
thought to exert its effect through glutathione synthesis. This study tested the
hypothesis that NAC enhances enterocyte growth and protein synthesis
independently of cellular glutathione synthesis. Intestinal porcine epithelial
cells were cultured for 3 days in Dulbecco's modified Eagle medium containing 0
or 100 MUM NAC. To determine a possible role for GSH (the reduced form of
glutathione) in mediating the effect of NAC on cell growth and protein synthesis,
additional experiments were conducted using culture medium containing 100 MUM
GSH, 100 MUM GSH ethyl ester (GSHee), diethylmaleate (a GSH-depletion agent; 10
MUM), or a GSH-synthesis inhibitor (buthionine sulfoximine, BSO; 20 MUM). NAC
increased cell proliferation, GSH concentration, and protein synthesis, while
inhibiting proteolysis. GSHee enhanced cell proliferation and GSH concentration
without affecting protein synthesis but inhibited proteolysis. Conversely, BSO or
diethylmaleate reduced cell proliferation and GSH concentration without affecting
protein synthesis, while promoting protein degradation. At the signaling level,
NAC augmented the protein abundance of total mTOR, phosphorylated mTOR, and
phosphorylated 70S6 kinase as well as mRNA levels for mTOR and p70S6 kinase in
IPEC-1 cells. Collectively, these results indicate that NAC upregulates
expression of mTOR signaling proteins to stimulate protein synthesis in
enterocytes independently of GSH generation. Our findings provide a hitherto
unrecognized biochemical mechanism for beneficial effects of NAC in intestinal
cells.
PMID- 26433893
TI - Implications of a pre-exercise alkalosis-mediated attenuation of HSP72 on its
response to a subsequent bout of exercise.
AB - The aim of this study was to investigate if a pre-exercise alkalosis-mediated
attenuation of HSP72 had any effect on the response of the same stress protein
after a subsequent exercise. Seven physically active males [25.0 +/- 6.5 years,
182.1 +/- 6.0 cm, 74.0 +/- 8.3 kg, peak aerobic power (PPO) 316 +/- 46 W]
performed a repeated sprint exercise (EXB1) following a dose of 0.3 g kg(-1) body
mass of sodium bicarbonate (BICARB), or a placebo of 0.045 g kg(-1) body mass of
sodium chloride (PLAC). Participants then completed a 90-min intermittent cycling
protocol (EXB2). Monocyte expressed HSP72 was significantly attenuated after EXB1
in BICARB compared to PLAC, however, there was no difference in the HSP72
response to the subsequent EXB2 between conditions. Furthermore there was no
difference between conditions for measures of oxidative stress (protein carbonyl
and HSP32). These findings confirm the sensitivity of the HSP72 response to
exercise-induced changes in acid-base status in vivo, but suggest that the
attenuated response has little effect upon subsequent stress in the same day.
PMID- 26433894
TI - Psychiatric disorders in Ehlers-Danlos syndrome are frequent, diverse and
strongly associated with pain.
AB - Ehlers-Danlos syndromes (EDS) are a heterogeneous group of hereditary connective
tissue disorders characterized by joint hypermobility, widespread musculoskeletal
pain and tissue fragility. Psychiatric disorders and psychosocial impairment are
common, yet poorly characterized, findings in EDS patients. We investigated the
frequency and types of psychiatric disorders and their relationship to systemic
manifestations in a cohort of 106 classic and hypermobility type EDS patients. In
this retrospective study, extensive medical chart review was performed for
patients referred at two genetics clinics who were diagnosed with EDS.
Statistical analysis was undertaken to determine the frequency of psychiatric
disorders and association with systemic findings. Psychiatric disorders were
found in 42.5% of the EDS cohort, with 22.7% of patients affected with 2 or more
psychiatric diagnoses. Anxiety and depression were most commonly reported, with
frequencies of 23.6 and 25.5%, respectively. A variety of other psychiatric
diagnoses were also identified. Abdominal pain [odds ratio (OR) 7.38],
neuropathic pain (OR 4.07), migraines (OR 5.21), joint pain (OR 2.85) and fatigue
(OR 5.55) were significantly associated with the presence of a psychiatric
disorder. The presence of any pain symptom was significantly associated with
having a psychiatric disorder (OR 9.68). Muscle pain (OR 2.79), abdominal pain
(OR 5.78), neuropathic pain (OR 3.91), migraines (OR 2.63) and fatigue (OR 3.78)
were significantly associated with having an anxiety or mood disorder. Joint
hypermobility and the classic dermatological features of EDS showed no
significant association with having a psychiatric disorder. Our findings
demonstrate a high frequency of psychiatric disorders and an association with
pain symptoms in EDS.
PMID- 26433895
TI - The validity of a non-radiologist reader in identifying cam and pincer
femoroacetabular impingement (FAI) using plain radiography.
AB - The purpose of this study was to evaluate the validity and reliability of a
radiographic diagnosis of femoroacetabular impingement (FAI) by a non
radiologist. Symptomatic FAI is prevalent and thought to be a cause of hip
osteoarthritis. However, the diagnosis is often delayed by 1-2 years, in large
part because radiographic findings are often subtle and clinicians have been
unaware of their significance. The purpose of this study was to evaluate the
validity of a radiographic diagnosis of FAI by a non-radiologist. A population
based sample of 701 subjects was recruited in Vancouver, Canada. For the current
study, 50 subjects were selected-40 randomly from the population sample and 10
from an orthopedic practice with confirmed FAI. An anterior-posterior pelvis and
bilateral Dunn radiographs were acquired and read by a fellowship-trained
musculoskeletal radiologist and a third-year medical student who received basic
training in radiographic signs of FAI. Three radiographic signs were evaluated:
the lateral center edge angle, alpha angle and crossover sign. Validity was
assessed using sensitivity and specificity, Bland-Altman limits of agreement and
kappa. The sample contained 65% women (n = 31), was 62% Caucasian and 38% Chinese
and had a mean age of 38.3 years. For correctly diagnosing FAI, the non
radiologist reader had a sensitivity of 0.83 and specificity of 0.87. Intra-rater
kappa value was 0.72, and prevalence-adjusted bias-adjusted kappa was 0.76. This
study provides evidence that a non-radiologist can accurately and reliably
identify FAI on plain films.
PMID- 26433896
TI - Aluminium stress disrupts metabolic performance of Plantago almogravensis
plantlets transiently.
AB - Little is known about how tolerant plants cope with internalized aluminium (Al).
Tolerant plants are known to deploy efficient detoxification mechanisms, however
it is not known to what extent the primary and secondary metabolism is affected
by Al. The aim of this work was to study the metabolic repercussions of Al stress
in the tolerant plant Plantago almogravensis. P. almogravensis is well adapted to
acid soils where high concentrations of free Al are found and has been classified
as a hyperaccumulator. In vitro reared plantlets were used for this purpose in
order to control Al exposure rigorously. The metabolome of P. almogravensis
plantlets as well as its metabolic response to the supply of sucrose was
characterized. The supply of sucrose leads to an accumulation of amino acids and
secondary metabolites and consumption of carbohydrates that result from increased
metabolic activity. In Al-treated plantlets the synthesis of amino acids and
secondary metabolites is transiently impaired, suggesting that P. almogravensis
is able to recover from the Al treatment within the duration of the trials. In
the presence of Al the consumption of carbohydrate resources is accelerated. The
content of some metabolic stress markers also demonstrates that P. almogravensis
is highly adapted to Al stress.
PMID- 26433897
TI - Effect of manganese treatment on the accumulation on biologically relevant metals
in rat cochlea and brain by inductively coupled plasma mass spectrometry.
AB - Manganese (Mn), iron (Fe), zinc (Zn), and copper (Cu) are essential transitions
metals that are required in trace amounts, however chronic exposure to high
concentrations can cause severe and irreversible neurotoxicity. Since prolonged
exposure to Mn leads to manganism, a disorder exhibiting a diverse array of
neurological impairments progressing to a debilitating and irreversible
extrapyramidal condition symptomatically similar to Parkinson's disease, we
measured the concentration of Mn as well as Fe, Zn and Cu in three region of the
brain (globus pallidus, striatum and inferior colliculus) and three regions in
the cochlea (stria vascularis, basilar membrane and modiolus) under normal
conditions or after 30 or 60 days of oral administration of Mn (10 mg/ml ad
libitum). Under normal conditions, Mn, Zn and Fe were typically higher in the
cochlea than in the three brain regions whereas Cu was equal to or lower. Oral
treatment with Mn for 30 or 60 days resulted in 20-75 % increases in Mn
concentrations in both cochlea and brain samples, but had little effect on Cu and
Fe levels. In contrast, Zn levels decreased (20-80 %) with Mn exposure. Our
results show for the first time how prolonged oral Mn-ingestion affects the
concentration of Mn, Cu, Zn and Fe, in the three regions of the cochlea, the
inferior colliculus in auditory midbrain and the striatum and globus pallidus,
two regions implicated in Parkinson's disorder. The Mn-induced changes in the
concentration of Mn, Cu, Zn and Fe may provide new insights relevant to the
neurotoxicity of Mn and the transport and accumulation of these metals in cochlea
and brain.
PMID- 26433898
TI - Are Callous-Unemotional Traits Associated with Conflict Adaptation in Childhood?
AB - This study examined associations between childhood callous-unemotional (CU)
traits and cognitive control using a conflict adaptation paradigm. Participants
were (N = 158) children aged 9 to 12 years (M = 10.42, SD = 1.05; 57 % boys), who
completed a modified color-word Stroop task. CU traits and conduct problems were
indexed via self-reports on the Strengths and Difficulties Questionnaire and the
Inventory of Callous-Unemotional Traits. CU traits were found to be uniquely
associated with reduced conflict adaptation, however, this significant
association was specific to boys. Conversely, conduct problems were associated
with increased conflict adaptation, but among girls only. These findings
contribute to evidence of atypical goal directed behavior in boys with CU traits
by providing preliminary evidence that the specific impairments in cognitive
control that characterize these boys include those concerning dynamic adjustments
in cognitive control. Findings are discussed in relation to accounts of childhood
CU traits based on the Response Modulation hypothesis.
PMID- 26433899
TI - Connectivity-Based Brain Parcellation: A Connectivity-Based Atlas for
Schizophrenia Research.
AB - Defining brain structures of interest is an important preliminary step in brain
connectivity analysis. Researchers interested in connectivity patterns among
brain structures typically employ manually delineated volumes of interest, or
regions in a readily available atlas, to limit the scope of connectivity analysis
to relevant regions. However, most structural brain atlases, and manually
delineated volumes of interest, do not take voxel-wise connectivity patterns into
consideration, and therefore may not be ideal for anatomic connectivity analysis.
We herein propose a method to parcellate the brain into regions of interest based
on connectivity. We formulate connectivity-based parcellation as a graph-cut
problem, which we solve approximately using a novel multi-class Hopfield network
algorithm. We demonstrate the application of this approach using diffusion tensor
imaging data from an ongoing study of schizophrenia. Compared to a standard
anatomic atlas, the connectivity-based atlas supports better classification
performance when distinguishing schizophrenic from normal subjects. Comparing
connectivity patterns averaged across the normal and schizophrenic subjects, we
note significant systematic differences between the two atlases.
PMID- 26433900
TI - Effects of soil contamination by trace elements on white poplar progeny: seed
germination and seedling vigour.
AB - Seed germination is considered a critical phase in plant development and
relatively sensitive to heavy metals. White poplar (Populus alba) trees tend to
accumulate Cd and Zn in their tissues. We tested if soil contamination can affect
P. alba progeny, reduced seed germination and explored the distribution of
mineral elements in the seed. For this purpose, fruits and seeds from female P.
alba trees were selected from two contaminated and one non-contaminated areas.
Seeds from all the sites were germinated using only water or a nutritive solution
(in vitro). Concentrations of nutrients and trace elements in the fruits and
seeds were analysed. Seedling growth in vitro was also analysed. Finally, a
mapping of different elements within the poplar seed was obtained by particle
induced X-ray emission (PIXE). Germination was similar between different
progenies, refuting our hypothesis that seeds from a contaminated origin would
have reduced germination capacity compared to those from a non-contaminated site.
Seedling growth was not affected by the contaminated origin. Cadmium and Zn
concentrations in fruits produced by P. alba trees in the contaminated sites were
higher than by those from the non-contaminated site. However, the nutritional
status of the trees was adequate in both cases. Cd in seedlings was higher in
those from contaminated soils although lower than in fruits, indicating a certain
exclusion from seeds. Preliminary results of the PIXE technique showed that Al
and Zn were distributed uniformly in the seeds (Cd was not detected with this
technique), while the nutrients P and S were concentrated in the cotyledons.
PMID- 26433901
TI - Microalgal diversity in relation to the physicochemical parameters of some
Industrial sites in Mangalore, South India.
AB - This study is undertaken to understand the microalgal species composition,
diversity, abundance and their association with the polluted sites of an
industrial area. The microalgae and the wastewater samples collected from these
sites were preserved and analysed using standard methods. One hundred and eight
species of the microalgae, belonging to Cyanophyceae, Chlorophyceae,
Euglenophyceae, Bacillariophyceace and Desmidaceae, were identified. Of these,
the members of Cyanophyceae formed the dominant flora. It was observed that the
family Oscillatoriaceae was the most diverse family. In this family, the most
diverse genus was found to be the Oscillatoria, with 13 species. Further, the
abundance of Oscillatoria princeps indicated that these species are tolerant to
the pollution and therefore considered as the 'marker species' of the habitat.
The abundance of the Cyanophyceae in these sites was found to be due to the
favourable contents of the oxidizable organic matter and the presence of the
nutrients, such as the nitrates and the phosphates, in abundance, with less
dissolved oxygen. The lesser percentage of the Bacillariophyceae (14%), and the
negligible number of the euglenoids (2%) indicated that the sites were rich in
the inorganic pollutants and poor in the organic pollutants. The range of Shannon
diversity indices was found between 2.10 and 3.50, while the dominance index was
found between 0.03 and 0.14, the species evenness between 0.73 and 0.93 and the
Margalef index between 1.8 and 6.3. The diversity indices indicated that there is
light to moderate level of pollution in the studied sites, with moderate
diversity level. The principal component analysis (PCA) of the physicochemical
parameters identified the four possible groups, which were responsible for the
data structure, explaining the 74% of the total variance of the data set. In the
PCA performed using all the variables, the first principal component showed the
positive correlation with the total dissolved solids (TDS), salinity,
conductivity, temperature, biochemical oxygen demand (BOD) and the sulphates and
the negative correlation with the dissolved oxygen (DO) and Pb2+. The second
principal component showed the positive correlation with the pH, dissolved
oxygen, chemical oxygen demand (COD), nitrates and phosphates, and the negative
correlation with the TDS, salinity, conductivity, temperature and BOD. The
canonical correspondence analysis (CCA) showed that there were significant
(p<0.05) positive and negative relationships between some of the physicochemical
parameters and the microalgal species at these sites. The results showed that
Calonies bacillum and Pseudanabaena amphigranulata were in close positive
association with the pH, DO, COD, chlorides, nitrates and Cu+2 at the third and
the fifth sites; the Navicula sphaerophora, Stigonema minutum and Chlamydomonas
sphagnicola were in close positive association with the phosphates and the lead
at the first, second and the fifth sites; the Anabaena spiroides, Anabaena
constricta, Oscillatoria curviceps, Oscillatoria princeps, Spirogyra pratensis,
Spirogyra crassa, Aulosira laxa and Micrasterias foliacea were in close positive
association with the conductivity and the BOD levels at the fourth site, while
the Phormidium acutum, Oedogonium decipiens, Oscillatoria trichoides and
Parapediastrum biradiatum were in close positive association with the TDS,
salinity, temperature, sulphate and Cr+6 levels at the first and the second
sites. Therefore, the variations in the physicochemical parameters in the waters
of these habitats are attributed to be the reasons for the differences in the
diversity and the distribution of the species. Further, the significant
correlations observed between the microalgal species and the physicochemical
parameters studied here suggest that the type of pollution can be predicted,
based on the structure of the microalgal community.
PMID- 26433902
TI - Groundwater-induced alterations in elemental concentration and interactions in
semi-arid soils of the Southern High Plains, USA.
AB - This study examined and compared arsenic (As) and other element [copper (Cu),
iron (Fe), potassium (K), manganese (Mn), rubidium (Rb), and zinc (Zn)]
distribution, as well as their interactions in historically irrigated and non
irrigated semi-arid agricultural soils of the Southern High Plains (SHP) in the
USA, using findings from a portable X-ray fluorescence spectrometer. The portable
X-ray fluorescence (PXRF) findings revealed that the concentrations of As (5.1
vs. 3.1 mg kg(-1)), Cu (7.2 vs. 6.2), Fe (7398 vs. 5677), K (8638 vs. 7061), Mn
(80 vs. 68), Rb (36 vs. 27), and Zn (19.3 vs. 13.8) were higher in the
historically irrigated field compared to the non-irrigated and, when examined
within depths, were consistently and significantly higher (P<0.001) in the
subsurface soils of the non-irrigated field, a trend not evident in the irrigated
field. The strengths of the correlation among elements were higher in the non
irrigated field compared to the irrigated (average R of 0.60 vs. 0.54),
suggesting a possible external input of these pollutants in the historically
irrigated field which could have altered the natural background concentration and
association among them. Furthermore, findings from principal component analysis
(PCA) indicated that As, Mn, Rb, Fe, Zn, and K were more closely associated in
the non-irrigated field and likely of lithogenic origin. The observed differences
in elemental concentration and interaction between the irrigated and non
irrigated soils support the hypothesis that water from the local aquifer could be
a potential source of pollutant addition to these semi-arid alkaline soils.
PMID- 26433903
TI - Prediction of blast-induced air overpressure: a hybrid AI-based predictive model.
AB - Blast operations in the vicinity of residential areas usually produce significant
environmental problems which may cause severe damage to the nearby areas. Blast
induced air overpressure (AOp) is one of the most important environmental impacts
of blast operations which needs to be predicted to minimize the potential risk of
damage. This paper presents an artificial neural network (ANN) optimized by the
imperialist competitive algorithm (ICA) for the prediction of AOp induced by
quarry blasting. For this purpose, 95 blasting operations were precisely
monitored in a granite quarry site in Malaysia and AOp values were recorded in
each operation. Furthermore, the most influential parameters on AOp, including
the maximum charge per delay and the distance between the blast-face and
monitoring point, were measured and used to train the ICA-ANN model. Based on the
generalized predictor equation and considering the measured data from the granite
quarry site, a new empirical equation was developed to predict AOp. For
comparison purposes, conventional ANN models were developed and compared with the
ICA-ANN results. The results demonstrated that the proposed ICA-ANN model is able
to predict blast-induced AOp more accurately than other presented techniques.
PMID- 26433904
TI - Synthesis and biological evaluation of strained unusual amino acid containing
tetrapeptides as potential antidepressant agents.
AB - Strained unusual amino acid derived tetrapeptides were synthesized as mimics of
GLYX-13, a clinical candidate for neuroprotective and anti-depressant properties,
were studied. The synthesized compounds were screened for neurite growth and anti
depressant properties in vitro and in vivo respectively comparing with the parent
GLYX-13 compound. Neurite growth property was assessed by neurite length and anti
depressant property by percentage of immobility in forced swim test, a
behavioural assay. Mechanistic insights about protein-ligand interactions were
obtained using molecular docking study. Based on the in vitro and in vivo
screening data and molecular docking study, a new analogue of GLYX-13, Compound
11a has been found to be as good as the parent compound in all respects.
PMID- 26433905
TI - Quantification of renal and diaphragmatic interfractional motion in pediatric
image-guided radiation therapy: A multicenter study.
AB - BACKGROUND AND PURPOSE: To quantify renal and diaphragmatic interfractional
motion in order to estimate systematic and random errors, and to investigate the
correlation between interfractional motion and patient-specific factors. MATERIAL
AND METHODS: We used 527 retrospective abdominal-thoracic cone beam CT scans of
39 childhood cancer patients (<18 years) to quantify renal motion relative to
bony anatomy in the left-right (LR), cranio-caudal (CC) and anterior-posterior
(AP) directions, and diaphragmatic motion in the CC direction only.
Interfractional motion was quantified by distributions of systematic and random
errors in each direction (standard deviations Sigma and sigma, respectively).
Also, correlation between organ motion and height was analyzed. RESULTS: Inter
patient organ motion varied widely, with the largest movements in the CC
direction. Values of Sigma in LR, CC, and AP directions were 1.1, 3.8, 2.1 mm for
the right, and 1.3, 3.0, 1.5 mm for the left kidney, respectively. The sigma in
these three directions was 1.1, 3.1, 1.7 mm for the right, and 1.2, 2.9, 2.1 mm
for the left kidney, respectively. For the diaphragm we estimated Sigma=5.2 mm
and sigma=4.0 mm. No correlations were found between organ motion and height.
CONCLUSIONS: The large inter-patient organ motion variations and the lack of
correlation between motion and patient-related factors, suggest that
individualized margin approaches might be required.
PMID- 26433906
TI - Evolving Therapeutic Options for Polycythemia Vera: Perspectives of the Canadian
Myeloproliferative Neoplasms Group.
AB - Polycythemia vera (PV) is a clonal stem cell disorder characterized by
erythrocytosis and associated with burdensome symptoms, reduced quality of life,
risk of thrombohemorrhagic complications, and risk of transformation to
myelofibrosis and acute myeloid leukemia. The discovery of the JAK2 V617 mutation
marked a significant milestone in understanding the pathophysiology of the
disease and subsequently the diagnostic and therapeutic approaches. The current
diagnostic criteria for PV are based on hemoglobin level and presence of the JAK2
V617 mutation. The treatment is geared toward prevention of thrombotic events,
normalization of blood counts, control of disease-related symptoms, and potential
prolongation of survival. Cytoreductive therapy is indicated in patients at
increased risk of thrombosis. Hydroxyurea (HU) remains the most commonly used
first-line cytoreductive therapy and is superior to phlebotomy in reducing risk
of arterial and venous thrombosis. Interferon (IFN) is used either at failure of
HU or in selected patients as first-line therapy. The results of pegylated IFN in
phase 2 studies appear encouraging, with molecular responses occurring in some
patients. Ongoing phase 3 studies of HU versus pegylated IFN will define the
optimal first-line cytoreductive therapy for PV. A recent phase 3 trial has shown
the superiority of the JAK1/2 inhibitor ruxolitinib in comparison to best
available treatment in HU-intolerant or -resistant patients. The therapeutic
landscape of PV is likely to change in the near future. In this report, we assess
the potential impact of the changing landscape of PV management on daily
practice.
PMID- 26433907
TI - Monitoring Chronic Myeloid Leukemia in the Real World: Gaps and Opportunities.
AB - In clinical trials, in which treatment algorithms and monitoring schedules are
tightly prescribed by research protocols, outcomes for patients with chronic
myeloid leukemia (CML) have been excellent, with > 90% 5-year survival rates.
However, outside of clinical trials in the so-called real world, monitoring
schedules are more variable, with < 40% of patients undergoing quantitative
polymerase chain reaction (qPCR) molecular testing 3 to 4 times during the first
year after diagnosis as recommended by National Comprehensive Cancer
Network/European Leukemia Net (NCCN/ELN) evidence-based guidelines. Results from
chart reviews, claims-based databases, and observational databases suggest that
carefully monitored patients with CML are more likely to be adherent to
medications, incur fewer hospitalizations, experience lower overall treatment
costs, and have better progression-free survival and overall survival compared
with patients who are not monitored. Regular monitoring provides valuable early
information on treatment responses that physicians can use to modify treatment.
Unfortunately, physician-perceived resource barriers, lack of familiarity, and
lack of agreement have restricted monitoring guideline adoptions. Multifaceted
approaches to encourage appropriate monitoring are needed to improve clinical
outcomes and reduce costs in the real world.
PMID- 26433908
TI - More on Scylla and Charybdis.
PMID- 26433910
TI - Assessing cardiac and kidney protective effects by remote ischemic
preconditioning in cardiac surgery patients.
PMID- 26433909
TI - Sitagliptin use and risk of acute pancreatitis in type 2 diabetes mellitus: A
population-based case-control study in Taiwan.
AB - BACKGROUND: There is still lack of definite evidence to establish the association
between sitagliptin use and acute pancreatitis. The study aimed to test this
issue in Taiwan. METHODS: This case-control study was designed to analyze the
database of the Taiwan National Health Insurance Program. There were 349 subjects
with type 2 diabetes mellitus aged 20-84 with a first-attack of acute
pancreatitis from 2009 to 2011 as the case group and 1116 randomly selected
subjects with type 2 diabetes mellitus without acute pancreatitis as the control
group. Both groups were matched with sex, age, comorbidities, and index year of
diagnosing acute pancreatitis. Current use of sitagliptin was defined as subjects
who had their last tablet of sitagliptin <=7 days before the date of diagnosing
acute pancreatitis. Late use of sitagliptin was defined as subjects who had their
last tablet of sitagliptin between 8 and 30 days before the date of diagnosing
acute pancreatitis. Never use of sitagliptin was defined as subjects who never
had a sitagliptin prescription. The risk of acute pancreatitis associated with
sitagliptin use was estimated by the odds ratio (OR) and 95% confidence interval
(CI) using the multivariable logistic regression model. RESULTS: After
statistical correction for potential confounders, the adjusted OR of acute
pancreatitis was 2.47 for subjects with current use of sitagliptin (95% CI 0.84,
7.28), when compared with those never using sitagliptin, but without statistical
significance. The adjusted OR decreased to 1.14 for subjects with late use of
sitagliptin (95% CI 0.66, 1.98), but without statistical significance.
CONCLUSIONS: No significant association is detected between sitagliptin use and
acute pancreatitis in type 2 diabetes mellitus.
PMID- 26433911
TI - Resistance to conventional cardiopulmonary resuscitation in witnessed out-of
hospital cardiac arrest patients with shockable initial cardiac rhythm.
AB - BACKGROUND: Shockable initial cardiac rhythm is a key predictor of survival after
out-of-hospital cardiac arrest (OHCA). However, not all patients with shockable
OHCA achieve return of spontaneous circulation (ROSC) via conventional
cardiopulmonary resuscitation (CPR). Therefore, we retrospectively analyzed
patients with witnessed OHCA and shockable initial cardiac rhythm to identify the
resistance factors for conventional CPR. METHODS: We retrospectively analyzed
consecutive patients with witnessed OHCA and shockable initial cardiac rhythm who
were admitted to our hospital between October 2009 and October 2014. We then
compared the baseline characteristics, pre-hospital clinical course, and causes
of the cardiopulmonary arrest among patients who achieved ROSC via conventional
CPR and patients who did not achieve ROSC via conventional CPR and underwent
extracorporeal CPR (ECPR). RESULTS: A total of 85 patients achieved ROSC via
conventional CPR (non-ECPR group) and 40 patients did not achieve ROSC via
conventional CPR and underwent ECPR (ECPR group). Among these 125 patients, 113
had known causes for their cardiopulmonary arrest, including 66 cases (53%) of
acute myocardial infarction (AMI). There were no significant differences in the
causes of arrest between the non-ECPR and ECPR cases. However, among the 66 cases
of AMI (43 non-ECPR and 23 ECPR), the rate of non-recanalization during the
initial coronary angiography was significantly higher among the ECPR cases (non
ECPR: 58% vs. ECPR: 87%; p=0.03). CONCLUSIONS: The major cause of witnessed OHCA
with shockable initial cardiac rhythm was AMI, and resistance to conventional CPR
was related to continuous myocardial ischemia.
PMID- 26433912
TI - Subclinical elevation of high-sensitive troponin T levels at the convalescent
stage is associated with increased 5-year mortality after ST-elevation myocardial
infarction.
AB - BACKGROUND: It is unclear whether serum high-sensitive troponin T (hs-TnT) levels
at the convalescent stage of ST-elevation myocardial infarction (STEMI) are
associated with long-term mortality. METHODS: This study enrolled a total of 2944
consecutive STEMI patients who were registered in the Osaka Acute Coronary
Insufficiency Study between 2000 and 2009, and whose hs-TnT levels were evaluated
at the convalescent stage. Patients were divided into four hs-TnT category groups
according to the results of survival classification and regression tree (CART)
analysis. The impact of hs-TnT levels on 5-year mortality was evaluated using
multivariate Cox regression analysis. RESULTS: Only one patient had hs-TnT level
below the detection limit of the assay (<0.003ng/mL). The median hs-TnT level was
0.025 (quartile 0.011-0.083)ng/mL. During the median follow-up period of 1782
days, 188 patients died. Survival CART analysis revealed that the 1st, 2nd, and
3rd discriminating hs-TnT levels to discern 5-year mortality were 0.028, 0.008,
and 1.340ng/mL, respectively. The adjusted hazard ratios for the medium-low
(0.009-0.028ng/mL), medium-high (0.029-1.340ng/mL), and high-risk (>=1.341ng/mL)
groups were 3.03 (95% confidence interval 1.18-7.77, p=0.021), 4.29 (1.63-11.28,
p=0.003), and 8.68 (2.20-34.27, p=0.002), respectively. Integrated discrimination
improvement (IDI) analysis revealed that incorporation of this hs-TnT
classification scheme with other clinical variables statistically improved the
discriminatory accuracy for 5-year mortality, with a time-dependent IDI of 0.0076
(p=0.033). CONCLUSIONS: hs-TnT levels at the convalescent stage were associated
with long-term mortality in STEMI patients. Even subclinical elevation of hs-TnT
levels was associated with increased 5-year mortality.
PMID- 26433914
TI - Medical frontiers in an ancient desert.
PMID- 26433913
TI - Validity and reliability of an IMU-based method to detect APAs prior to gait
initiation.
AB - Anticipatory postural adjustments (APAs) prior to gait initiation have been
largely studied in traditional, laboratory settings using force plates under the
feet to characterize the displacement of the center of pressure. However clinical
trials and clinical practice would benefit from a portable, inexpensive method
for characterizing APAs. Therefore, the main objectives of this study were (1) to
develop a novel, automatic IMU-based method to detect and characterize APAs
during gait initiation and (2) to measure its test-retest reliability. Experiment
I was carried out in the laboratory to determine the validity of the IMU-based
method in 10 subjects with PD (OFF medication) and 12 control subjects.
Experiment II was carried out in the clinic, to determine test-retest reliability
of the IMU-based method in a different set of 17 early-to-moderate, treated
subjects with PD (tested ON medication) and 17 age-matched control subjects.
Results showed that gait initiation characteristics (both APAs and 1st step)
detected with our novel method were significantly correlated to the
characteristics calculated with a force plate and motion analysis system. The
size of APAs measured with either inertial sensors or force plate was
significantly smaller in subjects with PD than in control subjects (p<0.05). Test
retest reliability for the gait initiation characteristics measured with inertial
sensors was moderate-to-excellent (0.56= 3 months). Almost 50 % of the patients who
presented to the ED for evaluation of abscess were diagnosed with abscess while
the remaining patients were diagnosed with mastitis. Appropriate clinical and/or
imaging follow-up occurred in 77 %. Long-term follow-up (>= 3 months) occurred
more frequently in patients older than 30 years of age. Appropriate follow-up
does not occur in approximately one fourth of cases, suggesting that additional
clinician and patient education is warranted.
PMID- 26433917
TI - Group B streptococci screening.
PMID- 26433918
TI - Did self-sampling improve the adherence to group B streptococci screening in
pregnant women?
PMID- 26433920
TI - Characterising skeletal muscle under large strain using eccentric and Fourier
Transform-rheology.
AB - Characterising the passive anisotropic properties of soft tissues has been
largely limited to the linear viscoelastic regime and shear loading is rarely
done in the large deformation regime, despite the physiological significance of
such properties. This paper demonstrates the use of eccentric rheology, which
allows the anisotropy of skeletal muscle to be investigated. The large amplitude
oscillatory strain properties of skeletal muscle were also investigated using
Fourier Transform-rheology. Histology was used to qualitatively assess the
microstructure changes induced by large strain. Results showed that skeletal
muscle was strongly anisotropic in the linear regime. The storage and loss moduli
were found to be significantly different (p<0.05) between the three fibre
alignment groups; for the group tested with fibres perpendicular to plane of
shear was 12.3+/-1.3 kPa and 3.0+/-0.35 kPa, parallel to shear direction was
10.6+/-1.2 kPa and 2.4+/-0.23 kPa, and perpendicular to shear direction was 5.5+/
0.90 kPa and 1.3+/-0.21 kPa. The appearance and growth of higher order harmonics
at large strain was different in the three testing directions indicating that the
anisotropy of muscle affects skeletal muscle behaviour in the nonlinear regime.
Histological analysis showed an increasing destruction of extracellular matrix
and the rearrangement of fibres with increasing strain indicating mechanical
damage at strains of larger than 10%. These microstructural changes could
contribute to the complex nonlinear behaviour in skeletal muscle. This paper
demonstrates a method of characterising the anisotropic properties in skeletal
muscle under large strain whilst giving meaningful information on the physical
response of tissue at various strains.
PMID- 26433919
TI - Developmental toxicity of the PBDE metabolite 6-OH-BDE-47 in zebrafish and the
potential role of thyroid receptor beta.
AB - 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) is both a
polybrominated diphenyl ether (PBDE) flame retardant metabolite and a marine
natural product. It has been identified both as a neurotoxicant in cell-based
studies and as a developmental toxicant in zebrafish. However, hydroxylated PBDE
metabolites are also considered thyroid hormone disruptors due to their
structural similarity to endogenous thyroid hormones. The purpose of this study
was to evaluate the effects of 6-OH-BDE-47 on a developmental pathway regulated
by thyroid hormones in zebrafish. Morphological measurements of development (head
trunk angle, otic vesicle length, and eye pigmentation) were recorded in embryos
at 30h post fertilization (hpf) and detailed craniofacial morphology was examined
in 4 day old larvae using cartilage staining. Exposure to 6-OH-BDE-47 resulted in
severe developmental delays. A 100nM concentration resulted in a 26% decrease in
head trunk angle, a 54% increase in otic vesicle length, and a 42% decrease in
eye pigmentation. Similarly, altered developmental morphology was observed
following thyroid receptor beta morpholino knockdown, exposure to the thyroid
hormone triiodothyronine (T3) or to thyroid disrupting chemicals (TDC; iopanoic
acid and propylthiouracil). The threshold for lower jaw deformities and
craniofacial cartilage malformations was at doses greater than 50nM. Of interest,
these developmental delays and effects were rescued by microinjection of TRbeta
mRNA during the 1-2 cell stage. These data indicate that OH-BDEs can adversely
affect early life development of zebrafish and suggest they may be impacting
thyroid hormone regulation in vivo through downregulation of the thyroid hormone
receptor.
PMID- 26433921
TI - Kinematic hand parameters in front crawl at different paces of swimming.
AB - The aim of this study was to investigate the evolution of kinematic hand
parameters (sweepback angle, angle of attack, velocity, acceleration and
orientation of the hand relative to the absolute coordinate system) throughout an
aquatic stroke and to study the possible modifications caused by a variation of
the swimming pace. Seventeen competitive swimmers swam at long distance, middle
distance and sprint paces. Parameters were calculated from the trajectory of
seven markers on the hand measured with an optoelectronic system. Results showed
that kinematic hand parameters evolve differently depending on the pace. Angle of
attack, sweepback angle, acceleration and orientation of the hand do not vary
significantly. The velocity of the hand increases when the pace increases, but
only during the less propulsive phases (entry and stretch and downsweep to
catch). The more the pace increases and the more the absolute durations of the
entry and stretch and downsweep to catch phases decrease. Absolute durations of
the insweep and upsweep phases remain constant. During these phases, the
propulsive hand forces calculated do not vary significantly when the pace
increases. The increase of swimming pace is then explained by the swimmer's
capacity to maintain propulsive phases rather than increasing the force
generation within each cycle.
PMID- 26433923
TI - Fitts's Law using lower extremity movement: Performance driven outcomes for
degenerative lumbar spinal stenosis.
AB - A paucity of objective outcome measures exists for assessing movement disorders,
including degenerative lumbar spinal stenosis (LSS). Fitts's Law provides a novel
approach to clinical outcome measurement since performance is resistant to
learning, and task difficulty can be altered. The objective of the present study
was to compare, using a Fitts's task, movement performance of individuals with
and without LSS to determine if motor difficulties that arise with LSS impede the
planning, initiation, or execution of deliberate lower limb movements. Twelve pre
surgical LSS patients and twelve control participants from the community
performed a Fitts's Law (foot reaching) task, while LSS participants also
completed pain and disability questionnaires. Fitts's Law was evident for both
groups, however the LSS group's movements were more adversely impacted as task
difficulty increased. Specifically, the LSS group's movement time and time to
peak velocity (ttPV) increased as task index of difficulty increased, while peak
velocity decreased. Correlations between ttPV and leg pain, and with stenosis
impairment severity respectively, provided evidence that less support leg pain
and less stenosis impairment severity yield faster ttPV in the moving leg at the
highest index of difficulty. Therefore a lower extremity Fitts's Law task
captured differences in the planning and execution of leg movements between
healthy and LSS populations.
PMID- 26433924
TI - Pediatric aggressive giant cell granuloma of nasal cavity.
AB - INTRODUCTION: Giant cell granuloma (GCG) is a non-neoplastic osseous
proliferative lesion of unknown etiology. Although a benign disease process, GCG
can be locally destructive. It is extremely rare to have a pediatric case of GCG
occurring in the nasal cavity with intracranial invasion. PRESENTATION OF CASE:
We report a case of an aggressive and recurrent giant cell granuloma with
intracranial invasion in a 10 years old female patient which was completely
excised with endoscopic craniofacial resection. DISCUSSION: A literature review
on pathogenesis, diagnosis and management is also performed. CONCLUSION: The most
common treatment for giant cell granuloma is surgery, ranging from simple
curettage to resection. However, it must be completely excised in cases of
aggressive and extensive lesion because of the high recurrence rate after
incomplete removal.
PMID- 26433922
TI - Enhancing vaccine safety capacity globally: A lifecycle perspective.
AB - Major vaccine safety controversies have arisen in several countries beginning in
the last decades of 20th century. Such periodic vaccine safety controversies are
unlikely to go away in the near future as more national immunization programs
mature with near elimination of target vaccine-preventable diseases that result
in relative greater prominence of adverse events following immunizations, both
true reactions and temporally coincidental events. There are several ways in
which vaccine safety capacity can be improved to potentially mitigate the impact
of future vaccine safety controversies. This paper aims to take a "lifecycle"
approach, examining some potential pre- and post-licensure opportunities to
improve vaccine safety, in both developed (specifically U.S. and Europe) and low-
and middle-income countries.
PMID- 26433926
TI - A pre-pubertal girl with giant juvenile fibroadenoma: A rare case report.
AB - INTRODUCTION: Fibroadenomas are benign neoplasms usually arising between the ages
of 15-25 years. Approximately 0.4% fibroadenomas arise in juvenile age group.
Usually the diagnosis is straightforward by clinical examination and FNAC. But
sometimes rapid growth and giant size may pose difficulty in clinical approach.
CASE PRESENTATION: In this paper we are presenting a rare case of giant juvenile
fibroadenoma in a 10 years old girl which was diagnosed by FNAC and treated by
excision. Diagnosis was confirmed by histopathology. DISCUSSION: Giant juvenile
fibroadenomas are over 5cm in diameter and tend to show rapid growth mimicking a
carcinoma. But histological features are similar to smaller fibroadenomas and can
be enucleated. CONCLUSION: Through this case we want to emphasize that these
giant benign neoplasms should be suspected in any pre-pubertal girl with breast
lump and should always be treated with breast conserving surgery.
PMID- 26433925
TI - Intradiploic epidermoid cyst with intracranial hypertension syndrome: Report of
two cases and literature review.
AB - INTRODUCTION: Intradiploic epidermoid intracranial cysts (IEIC) derive from
ectodermal cells and are covered with stratified squamous epithelium. They are
extremely rare, and most common locations are in the occipital, frontal and
parietal bones. They have a very slow growth and can be asymptomatic until
becoming evident by the deformation produced. The treatment is based on the
removal of the lesion, and subsequent histopathological confirmation.
PRESENTATION OF CASE: Two cases are reported, with intracranial hypertension
syndrome, which is very uncommon because of the slow growth of this type of
pathology; however, decompensations occurring in the space-occupying lesions at
intracranial level explain this type of clinical presentation. DISCUSSION: The
most common presentation of intracranial intradiploic epidermoid cysts (IEIC) is
asymptomatically, which is made evident by the prominence at the level of the
soft tissues and then presenting less frequently local pain and cephalea; rarely
the size of the lesion can cause focal neurological signs. CONCLUSION: These
benign lesions, although they are of low incidence, are seen very rarely in
intradiploic locations and above all, of significant size, may produce
significant mass effect in patients, which was initially tolerated because of its
slow growth, however, they may become decompensate and cause intracranial
hypertension syndrome.
PMID- 26433927
TI - A rare cause of root-compression: Subaxial cervical synovial cyst in association
with congenital fusion.
AB - INTRODUCTION: Synovial cyst in the cervical spine is a very rare pathology that
develops from the facet joint. When a synovial cyst emerges into the surrounding
space, it can compress the nervous tissue and cause neurological symptoms. In the
cervical area there is additionally the risk of spinal cord compression comparing
to the more common presentation of synovial cysts in the lumbar spine.
PRESENTATION OF CASE: Here, a cervical synovial cysts from the left facet joint
grew into the spinal canal and compressed the C8 nerve root which led to root
compressing symptoms. Interestingly we found this synovial cyst with congenital
fusion. We identified only nine similar cases in the literature. The cyst was
removed surgically and the patient discharged without complications. DISCUSSION:
Numerous theories have been established to explain the pathogenesis of synovial
cyst. Biomechanical alterations of the spine play a significant role in the
development of synovial cyst. However, the etiology is still unclear. CONCLUSION:
Surgical treatment should be considered in cervical synovial cysts with
neurologic deficit or with cord compression or when the conservative treatment is
ineffective.
PMID- 26433928
TI - Extending Shelf Life Just Makes Sense.
PMID- 26433930
TI - Ontogenetic patterns in the dreams of women across the lifespan.
AB - The present study supports and extends previous research on the developmental
differences in women's dreams across the lifespan. The participants included 75
Canadian women in each of 5 age groups from adolescence to old age including 12
17, 18-24, 25-39, 40-64, and 65-85, totaling 375 women. One dream per participant
was scored by two independent judges using the method of content analysis. Trend
analysis was used to determine the ontogenetic pattern of the dream content
categories. Results demonstrated significant ontogenetic decreases (linear
trends) for female and familiar characters, activities, aggression, and
friendliness. These patterns of dream imagery reflect the waking developmental
patterns as proposed by social theories and recognized features of aging as
postulated by the continuity hypothesis. Limitations and suggestions for future
research including the examining of developmental patterns in the dreams of males
are discussed.
PMID- 26433929
TI - Voxelwise atlas rating for computer assisted diagnosis: Application to congenital
heart diseases of the great arteries.
AB - Atlas-based analysis methods rely on the morphological similarity between the
atlas and target images, and on the availability of labelled images. Problems can
arise when the deformations introduced by pathologies affect the similarity
between the atlas and a patient's image. The aim of this work is to exploit the
morphological dissimilarities between atlas databases and pathological images to
diagnose the underlying clinical condition, while avoiding the dependence on
labelled images. We propose a voxelwise atlas rating approach (VoxAR) relying on
multiple atlas databases, each representing a particular condition. Using a local
image similarity measure to assess the morphological similarity between the atlas
and target images, a rating map displaying for each voxel the condition of the
atlases most similar to the target is defined. The final diagnosis is established
by assigning the condition of the database the most represented in the rating
map. We applied the method to diagnose three different conditions associated with
dextro-transposition of the great arteries, a congenital heart disease. The
proposed approach outperforms other state-of-the-art methods using annotated
images, with an accuracy of 97.3% when evaluated on a set of 60 whole heart MR
images containing healthy and pathological subjects using cross validation.
PMID- 26433931
TI - Cytopathology of the trachea of Bombyx mori (Lepidoptera: Bombycidae) to Bombyx
mori nucleopolyhedrovirus.
AB - Bombyx mori is a holometabolous insect found only in germplasm banks and
morphological data related of resistance and susceptibility to diseases is
important when selecting hybrids for commercial and scientific interest. This
study analyzed the cytopathology of B. mori trachea to BmNPV, isolated
geographically in Parana state, Brazil. Fifth instar larvae were divided into two
groups, control and inoculated; the viral suspension used was 2.4*10(7)
polyhedral occlusion bodies/mL. From the second to the ninth day post
inoculation, segments of silkworm organs, containing the trachea, were processed
for transmission electron microscopy. Analyses of fresh hemolymph were also
performed to verify the susceptibility of the hemocytes. Signs of infection were
initially detected in the hemocytes and in the tracheal cells on the second and
fourth post-inoculation days, respectively. The cytopathology of the trachea
showed all stages of the viral cycle, which was the same as in other tissues.
Virions were detected in the basal lamina, which showed structural
disorganization. So, the infection time of the hemocytes prior to trachea and the
presence of virus in basal lamina, suggests that the trachea was a secondary
target, infected by budded virus coming from the hemolymph.
PMID- 26433933
TI - Age-dependent gait abnormalities in mice lacking the Rnf170 gene linked to human
autosomal-dominant sensory ataxia.
AB - Really interesting new gene (RING) finger protein 170 (RNF170) is an E3 ubiquitin
ligase known to mediate ubiquitination-dependent degradation of type-I inositol
1,4,5-trisphosphate receptors (ITPR1). It has recently been demonstrated that a
point mutation of RNF170 gene is linked with autosomal-dominant sensory ataxia
(ADSA), which is characterized by an age-dependent increase of walking
abnormalities, a rare genetic disorder reported in only two families. Although
this mutant allele is known to be dominant, the functional identity thereof has
not been clearly established. Here, we generated mice lacking Rnf170 (Rnf170(-/
)) to evaluate the effect of its loss of function in vivo. Remarkably, Rnf170(-/
) mice began to develop gait abnormalities in old age (12 months) in the form of
asynchronous stepping between diagonal limb pairs with a fixed step sequence
during locomotion, while age-matched wild-type mice showed stable gait patterns
using several step sequence repertoires. As reported in ADSA patients, they also
showed a reduced sensitivity for proprioception and thermal nociception. Protein
blot analysis revealed that the amount of Itpr1 protein was significantly
elevated in the cerebellum and spinal cord but intact in the cerebral cortex in
Rnf170(-/-) mice. These results suggest that the loss of Rnf170 gene function
mediates ADSA-associated phenotypes and this gives insights on the cure of
patients with ADSA and other age-dependent walking abnormalities.
PMID- 26433932
TI - APP overexpression in the absence of NPC1 exacerbates metabolism of amyloidogenic
proteins of Alzheimer's disease.
AB - Amyloid-beta (Abeta) peptides originating from beta-amyloid precursor protein
(APP) are critical in Alzheimer's disease (AD). Cellular cholesterol
levels/distribution can regulate production and clearance of Abeta peptides,
albeit with contradictory outcomes. To better understand the relationship between
cholesterol homeostasis and APP/Abeta metabolism, we have recently generated a
bigenic ANPC mouse line overexpressing mutant human APP in the absence of Niemann
Pick type C-1 protein required for intracellular cholesterol transport. Using
this unique bigenic ANPC mice and complementary stable N2a cells, we have
examined the functional consequences of cellular cholesterol sequestration in the
endosomal-lysosomal system, a major site of Abeta production, on APP/Abeta
metabolism and its relation to neuronal viability. Levels of APP C-terminal
fragments (alpha-CTF/beta-CTF) and Abeta peptides, but not APP mRNA/protein or
soluble APPalpha/APPbeta, were increased in ANPC mouse brains and N2a-ANPC cells.
These changes were accompanied by reduced clearance of peptides and an increased
level/activity of gamma-secretase, suggesting that accumulation of APP-CTFs is
due to decreased turnover, whereas increased Abeta levels may result from a
combination of increased production and decreased turnover. APP-CTFs and Abeta
peptides were localized primarily in early-/late-endosomes and to some extent in
lysosomes/autophagosomes. Cholesterol sequestration impaired endocytic-autophagic
lysosomal, but not proteasomal, clearance of APP-CTFs/Abeta peptides. Moreover,
markers of oxidative stress were increased in vulnerable brain regions of ANPC
mice and enhanced beta-CTF/Abeta levels increased susceptibility of N2a-ANPC
cells to H2O2-induced toxicity. Collectively, our results show that cellular
cholesterol sequestration plays a key role in APP/Abeta metabolism and increasing
neuronal vulnerability to oxidative stress in AD-related pathology.
PMID- 26433935
TI - Synthesis and optimization of Fe2O3 nanofibers for chromate adsorption from
contaminated water sources.
AB - In this work, alpha-Fe2O3 nanofibers were synthesized via electrospinning and
characterized to observe optimal morphological and dimensional properties towards
chromate removal. The Fe2O3 nanofiber samples were tested in aqueous solutions
containing chromate (CrO4(2-)) to analyze their adsorption capabilities and
compare them with commercially-available Fe2O3 nanoparticles. Synthesized Fe2O3
nanofibers were observed with a variety of different average diameters, ranging
from 23 to 63 nm, while having a constant average grain size at 34 nm, point zero
charge at pH 7.1, and band gap at 2.2 eV. BET analysis showed an increase in
specific surface area with decreasing average diameter, from 7.2 to 59.2 m(2)/g,
due to the increased surface area-to-volume ratio with decreasing nanofiber size.
Based on CrO4(2-) adsorption isotherms at pH 6, adsorption capacity of the Fe2O3
nanofibers increased with decreasing diameter, with the 23 nm sized nanofibers
having an adsorption capacity of 90.9 mg/g, outperforming the commercially
available Fe2O3 nanoparticles by nearly 2-fold. Additionally, adsorption kinetics
was also analyzed, increasing with decreasing nanofiber diameter. The enhanced
performance of the nanofiber is suggested to be caused solely due to the
increased surface area, in part by its size and morphology. Electrospun Fe2O3
nanofibers provide a promising solution for effective heavy metal removal through
nanotechnology-integrated treatment systems.
PMID- 26433934
TI - A non-synonymous single-nucleotide polymorphism associated with multiple
sclerosis risk affects the EVI5 interactome.
AB - Despite recent progress in the characterization of genetic loci associated with
multiple sclerosis (MS) risk, the ubiquitous linkage disequilibrium operating
across the genome has stalled efforts to distinguish causative variants from
proxy single-nucleotide polymorphisms (SNPs). Here, we have identified through
fine mapping and meta-analysis EVI5 as the most plausible disease risk gene
within the 1p22.1 locus. We further show that an exonic SNP associated with risk
induces changes in superficial hydrophobicity patterns of the coiled-coil domain
of EVI5, which, in turns, affects the EVI5 interactome. Immunoprecipitation of
wild-type and mutated EVI5 followed by mass spectrometry generated a roster of
disease-specific interactors functionally linked to lipid metabolism. Among the
exclusive binding partners of the risk variant, we describe the novel interaction
with sphingosine 1-phosphate lyase (SGPL1)-a key enzyme for the creation of the
sphingosine-1 phosphate gradient, which is relevant to the pathogenic process and
therapeutic management of MS.
PMID- 26433936
TI - Enhanced removal of 8-quinolinecarboxylic acid in an activated carbon cloth by
electroadsorption in aqueous solution.
AB - The effect of the electrochemical treatment (potentiostatic treatment in a filter
press electrochemical cell) on the adsorption capacity of an activated carbon
cloth (ACC) was analyzed in relation with the removal of 8-quinolinecarboxylic
acid pollutant from water. The adsorption capacity of an ACC is quantitatively
improved in the presence of an electric field (electroadsorption process)
reaching values of 96% in comparison to 55% in absence of applied potential. In
addition, the cathodic treatment results in higher removal efficiencies than the
anodic treatment. The enhanced adsorption capacity has been proved to be
irreversible, since the removed compound remains adsorbed after switching the
applied potential. The kinetics of the adsorption processes is also improved by
the presence of an applied potential.
PMID- 26433937
TI - Biodegradability of iopromide products after UV/H2O2 advanced oxidation.
AB - Iopromide is an X-ray and MRI contrast agent that is virtually non-biodegradable
and persistent through typical wastewater treatment processes. This study
determined whether molecular transformation of iopromide in a UV/H2O2 advanced
oxidation process (AOP) can result in biodegradable products. The experiments
used iopromide labeled with carbon-14 on the aromatic ring to trace degradation
of iopromide through UV/H2O2 advanced oxidation and subsequent biodegradation.
The biotransformation assay tracked the formation of radiolabeled (14)CO2 which
indicated full mineralization of the molecule. The results indicated that AOP
formed biodegradable iopromide products. There was no (14)C released from the pre
AOP samples, but up to 20% of all radiolabeled carbon transformed into (14)CO2
over the course of 42 days of biodegradation after iopromide was exposed to
advanced oxidation (compared to 10% transformation in inactivated post-AOP
controls). In addition, the quantum yield of photolysis of iopromide was
determined using low pressure (LP) and medium pressure (MP) mercury lamps as
0.069 +/- 0.005 and 0.080 +/- 0.007 respectively. The difference in the quantum
yields for the two UV sources was not statistically significant at the 95%
confidence interval (p = 0.08), which indicates the equivalency of using LP or MP
UV sources for iopromide treatment. The reaction rate between iopromide and
hydroxyl radicals was measured to be (2.5 +/- 0.2) * 10(9) M(-1) s(-1). These
results indicate that direct photolysis is a dominant degradation pathway in
UV/H2O2 AOP treatment of iopromide. Other iodinated contrast media may also
become biodegradable after exposure to UV or UV/H2O2.
PMID- 26433938
TI - Individual Pulmonary Veins Outgrow Somatic Growth After Primary Sutureless Repair
for Total Anomalous Pulmonary Venous Drainage.
AB - Indications of sutureless repair (SR) for pulmonary vein anomalies have evolved
from re-operational SR for pulmonary vein stenosis after the repair of total
anomalous pulmonary venous drainage (TAPVD) to primary SR for TAPVD associated
with right atrial isomerism or isolated TAPVD with small individual pulmonary
veins (IPVs) and an unfavorable pulmonary vein anatomy. We sought to determine
whether small IPVs outgrow somatic growth after primary SR. Between 2004 and
2013, 21 children underwent primary SR for TAPVD: 13 with a functionally single
ventricle, 11 with right atrial isomerism, six with isolated TAPVD, and 13 with a
pulmonary venous obstruction. TAPVD types were supracardiac in nine, infracardiac
in 10, and mixed in two. Utilizing cardiac computed tomography (CT), the maximal
diameter of each IPV was measured, and pulmonary vein index (PVI, summation of
cross-sectional areas of all four IPVs divided by body surface area) was
calculated. There were five early deaths after SR. Among survivors, 10 had both
preoperative and postoperative cardiac CT at a 3.6-month median interval. On
postoperative cardiac CT, IPVs were patent in all patients except one who
developed a left lower pulmonary vein obstruction. There was a 71 +/- 48 %
postoperative increase in the actual diameter of all four IPVs, and PVI increased
significantly from 215 +/- 55 to 402 +/- 117 mm(2)/m(2) (P value = 0.005). IPVs
outgrew somatic growth after primary SR of TAPVD. Primary SR may be a useful
measure in TAPVD patients whose IPVs are small.
PMID- 26433939
TI - Exploring the Discussion of Risk of Sudden Cardiac Death.
AB - Sudden arrhythmic death syndrome (SADS), where death is secondary to cardiac
arrhythmia, is associated with several cardiac ion channelopathies, including
long QT syndrome and Brugada syndrome, as well as cardiomyopathies such as
hypertrophic cardiomyopathy and dilated cardiomyopathy. Many of these conditions
often present in childhood or adolescence. This study investigates how diagnoses
of cardiac diseases associated with SADS are communicated within families. A
questionnaire was distributed through cardiac disease-focused support groups and
organizations. Data from 114 parents who have a child with a SADS condition were
used for analysis. Based on the responses, parents explained the risk of SADS in
a straightforward manner and related the risk to the importance of compliance
with the prescribed treatment. Participants also found it difficult to determine
and enforce lifestyle modifications, manage individuals' emotional reactions,
convey the seriousness of the information without scaring their children, and
discuss the risk of SADS during these conversations. Concerns regarding disease
progression, length and quality of life, and treatment failures were also
expressed. Healthcare providers, the Internet, other affected people, visual
aids, and personal experience were all reported to be helpful for facilitating
these discussions. Services and resources requested by participants included
children's support groups, a counselor or psychologist, and child-oriented
materials. Increased understanding of how families discuss children's diagnosis
of SADS conditions will equip healthcare providers with the information to
address parental concerns and help facilitate meaningful and informative
discussions within families.
PMID- 26433941
TI - Type 2 diabetes and leucocyte DNA methylation: an epigenome-wide association
study in over 1,500 older adults.
AB - AIMS/HYPOTHESIS: Development of type 2 diabetes depends on environmental and
genetic factors. We investigated the epigenome-wide association of prevalent
diabetes with DNA methylation (DNAm) in peripheral blood. METHODS: DNAm was
measured in whole blood with the Illumina Infinium HumanMethylation450 BeadChip
in two subsamples of participants from the ESTHER cohort study. Cohort 1 included
988 participants, who were consecutively recruited between July and October 2000
and cohort 2 included 527 randomly selected participants. The association of DNAm
with prevalent type 2 diabetes at recruitment was estimated using median
regression analysis adjusting for sex, age, BMI, smoking behaviour, cell
composition and batch at 361,922 CpG sites. RESULTS: Type 2 diabetes was
prevalent in 16% of the participants, and diabetes was poorly controlled in 45%
of the diabetic patients. In cohort 1 (discovery) DNAm at 39 CpGs was
significantly associated with prevalent diabetes after correction for multiple
testing. In cohort 2 (replication) at one of these CpGs, DNAm was still
significantly associated. Decreasing methylation levels at cg19693031 with
increasing fasting glucose and HbA1c concentrations were observed using
restricted cubic spline analysis. In diabetic patients with poorly controlled
diabetes, the decrease in estimated DNAm levels was approximately 5% in
comparison with participants free of diagnosed diabetes.
CONCLUSIONS/INTERPRETATION: Cg19693031, which is located within the 3'
untranslated region of TXNIP, might play a role in the pathophysiology of type 2
diabetes. This result appears biologically plausible given that thioredoxin
interacting protein is overexpressed in diabetic animals and humans and 3'
untranslated regions are known to play a regulatory role in gene expression.
PMID- 26433940
TI - Fructose-enriched diet induces inflammation and reduces antioxidative defense in
visceral adipose tissue of young female rats.
AB - PURPOSE: The consumption of refined, fructose-enriched food continuously
increases and has been linked to development of obesity, especially in young
population. Low-grade inflammation and increased oxidative stress have been
implicated in the pathogenesis of obesity-related disorders including type 2
diabetes. In this study, we examined alterations in inflammation and
antioxidative defense system in the visceral adipose tissue (VAT) of fructose-fed
young female rats, and related them to changes in adiposity and insulin
sensitivity. METHODS: We examined the effects of 9-week fructose-enriched diet
applied immediately after weaning on nuclear factor kappaB (NF-kappaB)
intracellular distribution, and on the expression of pro-inflammatory cytokines
(IL-1beta and TNFalpha) and key antioxidative enzymes in the VAT of female rats.
Insulin signaling in the VAT was evaluated at the level of insulin receptor
substrate-1 (IRS-1) protein and its inhibitory phosphorylation on Ser307.
RESULTS: Fructose-fed rats had increased VAT mass along with increased NF-kappaB
nuclear accumulation and elevated IL-1beta, but not TNFalpha expression. The
protein levels of antioxidative defense enzymes, mitochondrial manganese
superoxide dismutase 2, and glutathione peroxidase, were reduced, while the
protein content of IRS-1 and its inhibitory phosphorylation were not altered by
fructose diet. CONCLUSIONS: The results suggest that fructose overconsumption
related alterations in pro-inflammatory markers and antioxidative capacity in the
VAT of young female rats can be implicated in the development of adiposity, but
do not affect inhibitory phosphorylation of IRS-1.
PMID- 26433943
TI - Report on the 4-h rule and National Emergency Access Target (NEAT) in Australia:
time to review.
AB - Objective The aim of the present study was to provide a summary of a systematic
review of literature reporting benefits and limitations of implementing National
Emergency Access Target (NEAT), a target stipulating that a certain proportion of
patients presenting to hospital emergency departments are admitted or discharged
within 4h of presentation. Methods A systematic review of published literature
using specific search terms, snowballing techniques applied to retrieved
references and Google searches was performed. Results are presented as a
narrative synthesis given the heterogeneity of included studies. Results Benefits
of a time-based target for emergency care are improved timeliness of emergency
care and reduced in-hospital mortality for emergency admissions to hospital.
Limitations centre on using a process measure (time) alone devoid of any
monitoring of patient outcomes, the threshold nature of a time target and the
fact that currently NEAT combines the measurement of clinical management of two
very different patient cohorts seeking emergency care: less acute patients
discharged home and more acute patients admitted to hospital. Conclusions Time
based access targets for emergency presentations are associated with significant
improvements in in-hospital mortality for emergency admissions. However, other
patient-important outcomes are deserving of attention, choice of targets needs to
be validated by empirical evidence of patient benefit and single targets need to
be partitioned into separate targets pertaining to admitted and discharged
patients. What is known about the topic? Time targets for emergency care
originated in the UK. The introduction of NEAT in Australia has been
controversial. NEAT directs that a certain proportion of patients will be
admitted or discharged from an emergency department (ED) within 4h. Recent
dissolution of the Australian National Partnership Agreement (which provided
hospitals with financial incentives for achieving NEAT compliance) has prompted a
re-examination of the 4-h rule, the evidence underpinning its introduction and
its benefits and risks to patients What does this paper add? This paper is
executive summary of key findings from a systematic literature review on the
benefits and limitations of NEAT (the 4-h rule) commissioned by the Queensland
Clinical Senate to inform future policy and targets. What are the implications
for practitioners? There is evidence that a time-based target has been associated
with a reduction in in-hospital mortality for emergency admissions to Australian
hospitals. Concerns remain regarding a time-based target alone being used to
drive redesign efforts at improving access to emergency care. A time-based target
should be coupled with close monitoring of patient outcomes of emergency care.
Target thresholds need to be evidence based and separate targets should be
reported for admitted, discharged and all patients presenting to the ED.
PMID- 26433942
TI - netCare, a new collaborative primary health care service based in Swiss community
pharmacies.
AB - BACKGROUND: The Swiss Pharmacists Association has launched a new collaborative
project, netCare. Community pharmacists provide a standard form with structured
triage based on decision trees and document findings. As a backup, they can
collaborate with physicians via video consultation. OBJECTIVE: The aim of the
study was to evaluate the impact of this service on the Swiss health care system.
METHOD: All pharmacists offering netCare completed two training courses, a course
covering the most common medical conditions observed in primary health care and a
specific course on all of the decision trees. The pharmacists were free to decide
whether they would provide the usual care or offer netCare triage. The patient
was also free to accept or refuse netCare. Pharmacists reported the type of
ailment, procedure of the consultation, treatment, patient information and
outcomes of the follow-up call on a standardized form submitted to the study
center. RESULTS: Pharmacists from 162 pharmacies performed 4118 triages over a
period of 21 months. A backup consultation was needed for 17% of the cases. In
follow-up calls, 84% of the patients who were seen only by pharmacists reported
complete relief or symptom reduction. CONCLUSIONS: netCare is a low-threshold
service by which pharmacists can manage common medical conditions with physician
backup, if needed. This study showed that a pharmacist could resolve a large
proportion of the cases. However, to be efficient and sustainable, this service
must be fully integrated into the health care system.
PMID- 26433945
TI - Prevalence of Hazardous Drinking Among UK 18-35 Year Olds; the Impact of a
Revision to the AUDIT Cut Score.
AB - AIM: Most published research utilizes an AUDIT score of >8 as the threshold for
hazardous drinking. Recent research suggests that this limit should be amended
for younger drinkers (aged 18-35 years). This study aimed to explore the effect
of a revision to AUDIT cut scores. METHOD: Applying Foxcroft et al.'s [(2015)
Accuracy of Alcohol Use Disorders Identification Test for detecting problem
drinking in 18-35 year-olds in England: method comparison study. Alcohol Alcohol
50, 244-50] suggested cut off scores of nine for males and four for females to
the most recent Adult Psychiatric Morbidity Survey (2007) data. RESULTS: This
more than doubles the prevalence of female hazardous drinkers, and significantly
increases the overall rate for that age group when compared with the standard
threshold of >8. CONCLUSION: The prevalence of hazardous drinking among females
ages 18-30 may be significantly higher than current estimates.
PMID- 26433944
TI - Impaired mitochondrial network excitability in failing guinea-pig cardiomyocytes.
AB - AIMS: Studies in guinea-pig cardiomyocytes show that reactive oxygen species
(ROS) produced by a few mitochondria can propagate to their neighbours,
triggering synchronized, cell-wide network oscillations via an ROS-induced ROS
release (RIRR) mechanism. How mitochondria in cardiomyocytes from failing hearts
(HF) respond to local oxidative stress perturbations has not been investigated.
Since mitochondrial ultrastructure is reportedly disrupted in HF, and propagation
of ROS signals depends on mitochondrial network integrity, we hypothesized that
the laser flash-induced RIRR is altered in HF. METHODS AND RESULTS: To test the
hypothesis, pressure-overload HF was induced in guinea pigs by ascending aortic
constriction leading to left ventricular dilatation and decreased ejection
fraction after 8 weeks. Isolated cardiomyocytes were studied with two
photon/confocal microscopy to determine their basal oxidative stress and
propensity to undergo mitochondrial depolarization/oscillations in response to
local laser flash stimulations. The expression of mitofusin proteins and
mitochondrial network structure were also analysed. Results showed that HF
cardiomyocytes had higher baseline ROS levels and less reduced glutathione, and
were more prone to laser flash-induced mitochondrial depolarization. In contrast,
the delay between the laser flash and synchronized cell-wide network oscillations
was prolonged in HF myocytes compared with shams, and the spatial extent of
coupling was diminished, suggesting dampened RIRR and ROS signal propagation. In
addition, the expressions of mitofusin proteins in HF myocardium were down
regulated compared with these from sham-operated animals, and the mitochondrial
network structure altered. CONCLUSION: The disrupted inter-mitochondrial
tethering and loss of structural organization may underlie decreased ROS
dependent mitochondrial coupling in HF.
PMID- 26433946
TI - The Benefits of Administering Folic Acid in Order to Combat the Oxidative Damage
Caused by Binge Drinking in Adolescent Rats.
AB - AIMS: An important mechanism in alcohol-induced injury is biomolecular oxidative
damage. Folic acid is supplied to chronic alcoholic patients in order to prevent
this situation, as this is the main vitamin deficiency that they suffer from.
Acute alcohol exposure, such as binge drinking, is one of the most widespread
ethanol consumption models practiced by adolescents. However, there is no
evidence of folic acid body profiles after this pattern of consumption. METHODS:
Four groups of adolescent rats were used: control, alcohol (exposed to
intraperitoneal binge drinking), control folic acid-supplemented group and
alcohol folic acid-supplemented group. Folic acid levels, protein, lipid and DNA
oxidative damage in serum, and liver glutathione (GSH) and reduced/oxidized
glutathione ratio (GSH/GSSG) were measured. RESULTS: Binge-drinking rats had
higher lipids and DNA oxidation levels. They also had lower hepatic GSH levels
and GSH/GSSG ratio. Folic acid supplementation to binge-drinking rats does not
change the serum protein oxidation but decreases lipid and DNA oxidation.
Finally, GSH increased to control levels with folic acid supplementation.
CONCLUSION: Folic acid supplementation is an economic and efficient therapy
against the oxidative damage in lipids and mainly in DNA stability caused by
binge drinking during adolescence. It has also been demonstrated that folic acid
increases GSH levels, improving the antioxidant status and revealing a
hepatoprotective effect during binge drinking.
PMID- 26433947
TI - Socioeconomic Disparities in Alcohol-Related Mortality in Sweden, 1991-2006: A
Register-Based Follow-Up Study.
AB - AIM: To examine whether apparent stability of overall alcohol-related mortality
in Sweden during a period when traditionally strict alcohol policies went through
a series of liberalizations and overall alcohol mortality remained stable,
concealed a heterogeneity across socioeconomic groups (defined by educational
level); and whether an increase occurred in the contribution of alcohol-related
mortality to overall mortality differentials. METHODS: Drawing on cause of death
data linked to census records for the period 1991-2006, we computed annual age
standardized and sex-specific rates of alcohol-related mortality for groups with
low, intermediate and high education. RESULTS: Alcohol-related mortality was
considerably higher in lower educational groups for both men and women. For men,
the trends in alcohol-related mortality were roughly stable for all education
groups, and there were no signs of increasing inequalities by education. For
women, alcohol-related mortality increased significantly for the low-education
group whereas the two higher education groups showed no significant time trends,
thus resulting in a widened educational gap in alcohol mortality for women.
Alcohol's contribution to the overall mortality differentials declined for men
and was basically unchanged for women. CONCLUSIONS: The findings provide only
partial support to the hypothesis that the liberalizations of Swedish alcohol
policy have been followed by a general increase in socioeconomic disparities in
alcohol-related mortality.
PMID- 26433950
TI - Editorial.
PMID- 26433948
TI - Next generation sequencing of triple negative breast cancer to find predictors
for chemotherapy response.
AB - INTRODUCTION: In triple negative breast cancers (TNBC) the initial response to
chemotherapy is often favorable, but relapse and chemotherapy resistance
frequently occur in advanced disease. Hence there is an urgent need for targeted
treatments in this breast cancer subtype. In the current study we deep sequenced
DNA of tumors prior to chemotherapy to search for predictors of response or
resistance. METHODS: Next generation sequencing (NGS) was performed for 1,977
genes involved in tumorigenesis. DNA from 56 pre-treatment TNBC-biopsies was
sequenced, as well as matched normal DNA. Following their tumor biopsy, patients
started neoadjuvant chemotherapy with doxorubicin and cyclophosphamide. We
studied associations between genetic alterations and three clinical variables:
chemotherapy response, relapse-free survival and BRCA proficiency. RESULTS: The
mutations observed were diverse and few recurrent mutations were detected. Most
mutations were in TP53, TTN, and PIK3CA (55 %, 14 %, and 9 %, respectively). The
mutation rates were similar between responders and non-responders (average
mutation rate 9 vs 8 mutations). No recurrent mutations were associated with
chemotherapy response or relapse. Interestingly, PIK3CA mutations were
exclusively observed in patients proficient for BRCA1. Samples with a relapse had
a higher copy number alteration rate, and amplifications of TTK and TP53BP2 were
associated with a poor chemotherapy response. CONCLUSIONS: In this homogenous
cohort of TNBCs few recurrent mutations were found. However, PIK3CA mutations
were associated with BRCA proficiency, which can have clinical consequences in
the near future.
PMID- 26433951
TI - Analysis of watermelon chlorotic stunt virus and tomato leaf curl Palampur virus
mixed and pseudo-recombination infections.
AB - Watermelon chlorotic stunt virus (WmCSV) and tomato leaf curl Palampur virus
(ToLCPMV) are limiting factors for cucurbit production in south and southeastern
Iran. ToLCPMV infects all cucurbit crops (except watermelons) whereas WmCSV is
somewhat limited to watermelon, causing detrimental effects on fruit production.
In a survey, we detected WmCSV in all watermelon growing farms in Fars province
(southern Iran). Given that WmCSV and ToLCPMV are present in the same
geographical location in Iran, we studied the interaction of two viruses. Co
infection using agroinfectious clones of WmCSV and ToLCPMV caused severe symptoms
in watermelon and zucchini in comparison to symptoms observed from individual
infections. Interestingly, inoculation of zucchini with WmCSV DNA-A and ToLCPMV
DNA-B agroinfectious clones or vice versa produced a viable pseudo-recombinant
and induced systemic symptoms. This demonstrates that replication-associated
protein of DNA-A of each virus is able to bind to cis elements of the DNA-B
molecules of another virus.
PMID- 26433952
TI - Patient-relevant needs and treatment goals in nail psoriasis.
AB - PURPOSE: Patient-centered health care implies that medical decisions are made
jointly by physician and patient, based on patient needs. Aims were to (a)
identify treatment goals for a new questionnaire on patient needs and benefits in
nail psoriasis treatment; (b) analyze the importance of treatment goals in
patients with nail psoriasis in general and in defined subgroups; and (c)
determine the association between overall treatment goal importance and quality
of life. METHODS: The study comprised the following steps: qualitative survey on
needs and burdens in 120 patients; development of items by an interdisciplinary
expert group; item testing in 55 patients in four countries; revision of the
questionnaire and assessment in 203 patients in six countries (Germany, Denmark,
Italy, Spain, USA, Japan). The percentage of patients rating the goals as
'quite/very important' was compared between various patient subgroups. RESULTS:
Based on 692 free-text statements, 26 items were developed which were reduced to
24 items after pilot testing. Each of these treatment goals applied to the
majority of patients in the multi-center study. Goal importance increased with
severity of nail psoriasis, but not with age or disease duration. Manual
dexterity and social interaction were of particular importance. Goal importance
and quality of life were associated, but not redundant (r = 0.612, p < 0.001).
CONCLUSIONS: Patients with nail psoriasis have manifold and specific treatment
goals. Goal importance is a construct different from disease-specific quality of
life and should be assessed separately. The new questionnaire can support goal
setting in clinical practice.
PMID- 26433953
TI - Validation of an innovative instrument of Positive Oral Health and Well-Being
(POHW).
AB - INTRODUCTION: Most existing measures of oral health focus solely on negative oral
health, illness, and deficiencies and ignore positive oral health. In an attempt
to commence exploration of this challenging field, an innovative instrument was
developed, the "Positive Oral Health and Well-Being" (POHW) index. This study
aimed to validate this instrument and to explore an initial model of the pathway
between oral health attributes and positive oral health. METHODS: A cross
sectional, multicenter study (Israel, USA, and Germany), was conducted. Our
conceptual model suggests that positive oral health attributes, which integrate
with positive unawareness or positive awareness on the one hand and with positive
perception on the other hand, may result via appropriate oral health behavior on
positive oral health. The 17-item self-administered index was built on a
theoretical concept by four experts from Israel and Germany. Reliability, factor,
and correlation analyses were performed. For external correlations and to measure
construct validity of the instrument, we utilized the oral health impact profile
14, self-perceived oral impairment, life satisfaction, self-perceived well-being,
sociodemographic and behavioral data, and oral health status indices. RESULTS:
Four hundred and seventy participants took part in our three-center study. The
combined data set reliability analyses detected two items which were not
contributing to the index reliability. Thus, we tested a 15-item construct, and a
Cronbach's alpha value of 0.933 was revealed. Primary factor analysis of the
whole sample indicated three subconstructs which could explain 60 % of variance.
Correlation analyses demonstrated that the POHW and OHIP-14 were strongly and
negatively associated. The POHW correlated strongly and positively with general
well-being, moderately with life satisfaction, and weakly with the perceived
importance of regular dental checkups. It correlated moderately and negatively
with perceived oral impairment, and marginally and negatively with dental caries
experience (DMFT) and periodontal health status (CPI) scores. When DMFT and CPI
clinical measurements were categorized, a higher score of POHW was revealed for
better oral health. DISCUSSION: Our study introduced a new instrument with good
reliability and sound correlations with external measures. This instrument is the
first to allow measurability of positive instead of impaired oral health. We
utilized subjective-psychological and functional-social measures. The current
results indicate that by further exploring our conceptual model, POHW may be of
importance for identifying patients with good and poor oral health, and building
an effective and inexpensive strategy for prevention, by being able to evaluate
the effect of interventions in a standardized way.
PMID- 26433954
TI - Managing CAP in the ICU.
AB - Despite remarkable progress in diagnosis and antibiotic therapy, mortality due to
pneumonia has not changed significantly and ICU admissions are increasing. The
management includes early evaluation of severity, collection of microbiological
cultures, and appropriate antibiotic administration. The prognostic scores as the
ATS/IDSA rule, the PIRO, or SCAP system are valuable in timely recognition of
critically ill patients with community-acquired pneumonia (CAP) requiring
admission to ICU. Implementation of guidelines for CAP treatment should be
emphasized in order to increase survival. Guidelines for antibiotic management
for severe CAP are based on illness severity, covering most likely bacterial and
atypical pathogens and the level of ICU antibiotic resistance. Combination
therapy suggested in patients with nonrefractory septic shock and severe sepsis
pneumococcal bacteremia also. Recent studies suggest that steroid therapy may be
valuable in nonrefractory septic shock from sCAP.
PMID- 26433955
TI - Increased synthesis of folate transporters regulates folate transport in
conditions of ethanol exposure and folate deficiency.
AB - Excessive alcohol consumption and dietary folate inadequacy are the main
contributors leading to folate deficiency (FD). The present study was planned to
study regulation of folate transport in conditions of FD and ethanol exposure in
human embryonic kidney cell line. Also, the reversible nature of effects mediated
by ethanol exposure and FD was determined by folate repletion and ethanol
removal. For ethanol treatment, HEK293 cells were grown in medium containing 100
mM ethanol, and after treatment, one group of cells was shifted on medium that
was free from ethanol. For FD treatment, cells were grown in folate-deficient
medium followed by shifting of one group of cells on folate containing medium. FD
as well as ethanol exposure resulted in an increase in folate uptake which was
due to an increase in expression of folate transporters, i.e., reduced folate
carrier, proton-coupled folate transporter, and folate receptor, both at the mRNA
and protein level. The effects mediated by ethanol exposure and FD were
reversible on removal of treatment. Promoter region methylation of folate
transporters remained unaffected after FD and ethanol exposure. As far as
transcription rate of folate transporters is concerned, an increase in rate of
synthesis was observed in both ethanol exposure and FD conditions. Additionally,
mRNA life of folate transporters was observed to be reduced by FD. An increased
expression of folate transporters under ethanol exposure and FD conditions can be
attributed to enhanced rate of synthesis of folate transporters.
PMID- 26433956
TI - Monitoring Crohn's disease during anti-TNF-alpha therapy: validation of the
magnetic resonance enterography global score (MEGS) against a combined clinical
reference standard.
AB - OBJECTIVES: To assess the ability of magnetic resonance enterography global score
(MEGS) to characterise Crohn's disease (CD) response to anti-TNF-alpha therapy.
METHODS: Thirty-six CD patients (median age 26 years, 20 males) commencing anti
TNF-alpha therapy with concomitant baseline MRI enterography (MRE) were
identified retrospectively. Patients' clinical course was followed and correlated
with subsequent MREs. Scan order was randomised and MEGS (a global activity
score) was applied by two blinded radiologists. A physician's global assessment
of the disease activity (remission, mild, moderate or severe) at the time of MRE
was assigned. The cohort was divided into clinical responders and non-responders
and MEGS compared according to activity status and treatment response.
Interobserver agreement was assessed. RESULTS: Median MEGS decreased
significantly between baseline and first follow-up in responders (28 versus 6, P
< 0.001) but was unchanged in non-responders (26 versus 18, P = 0.28). The median
MEGS was significantly lower in clinical remission (9) than in moderate (14) or
severe (29) activity (P < 0.001). MEGS correlated significantly with clinical
activity (r = 0.53; P < 0.001). Interobserver Bland-Altman limits of agreement
(BA LoA) were -19.7 to 18.5. CONCLUSIONS: MEGS decreases significantly in
clinical responders to anti-TNF-alpha therapy but not in non-responders,
demonstrates good interobserver agreement and moderate correlation with clinical
disease activity. KEY POINTS: * MRI scores of Crohn's activity are used
increasingly in clinical practice and therapeutic trials. * Such scores have been
advocated as biomarkers of therapeutic response. * MEGS reflects clinical
response to anti-TNF-alpha therapy and the clinical classification of disease
activity. * MEGS demonstrates good interobserver agreement.
PMID- 26433957
TI - Radiation dose reduction in paediatric coronary computed tomography: assessment
of effective dose and image quality.
AB - OBJECTIVES: To assess the impact of different protocols on radiation dose and
image quality for paediatric coronary computed tomography (cCT). MATERIALS AND
METHODS: From January-2012 to June-2014, 140 children who underwent cCT on a 64
slice scanner were included. Two consecutive changes in imaging protocols were
performed: 1) the use of adaptive statistical iterative reconstruction (ASIR); 2)
the optimization of acquisition parameters. Effective dose (ED) was calculated by
conversion of the dose-length product. Image quality was assessed as excellent,
good or with significant artefacts. RESULTS: Patients were divided in three age
groups: 0-4, 5-7 and 8-18 years. The use of ASIR combined to the adjustment of
scan settings allowed a reduction in the median ED of 58 %, 82 % and 85 % in 0-4,
5-7 and 8-18 years group, respectively (7.3 +/- 1.4 vs 3.1 +/- 0.7 mSv, 5.5 +/-
1.6 vs 1 +/- 1.9 mSv and 5.3 +/- 5.0 vs 0.8 +/- 2.0 mSv, all p < 0,05).
Prospective protocol was used in 51 % of children. The reduction in radiation
dose was not associated with reduction in diagnostic image quality as assessed by
the frequency of coronary segments with excellent or good image quality (88 %).
CONCLUSIONS: cCT can be obtained at very low radiation doses in children using
ASIR, and prospective acquisition with optimized imaging parameters. KEY POINTS:
* Using ASIR allows 25 % to 41 % reduction in the ED. * Prospective protocol is
used up to 51 % of children after premedication. * Low dose is possible using
ASIR and optimized prospective paediatric cCT.
PMID- 26433958
TI - Loss of heterozygosity for chromosomal regions 15q14-21.1, 17q21.31, and 13q12.3
13.1 and its relevance for prostate cancer.
AB - Although prostate cancer is one of the most common cancers in men, the genetic
defects underlying its pathogenesis remain poorly understood. DNA damage repair
mechanisms have been implicated in human cancer. Accumulating evidence indicates
that the fidelity of the response to DNA double-strand breaks is critical for
maintaining genome integrity. RAD51 is a central player in double-strand break
repair via homologous recombination, and its alterations may confer and increase
the risk of cancer. RAD51 functioning depends on the indirect or direct
interactions with BRCA1 and BRCA2. To evaluate the contribution of RAD51 to
sporadic prostate cancer, loss of heterozygosity (LOH) for chromosomal region
15q14-21.1 (RAD51 locus) was determined and compared to LOH in 17q21.31 (BRCA1
locus) and 13q12.3-13.1 (BRCA2 region). DNA was isolated from prostate biopsies
and matched peripheral blood of 50 patients. The regions 15q14-21.1, 17q21.31,
and 13q12.3-13.1 were examined using microsatellite markers on chromosome 15
(D15S118, D15S214, D15S1006), chromosome 17 (D17S855, D17S1323), and chromosome
13 (D13S260, D13S290), respectively. The LOH in tumors was analyzed by PCR with
fluorescently labeled primers and an ABI PRISM 377 DNA Sequencer. Allele sizing
was determined by GeneScan version 3.1.2 and Genotyper version 2.5 software
(Applied Biosystems, USA). LOH was identified in 57.5, 23, and 40 % for
chromosomal regions 15q14-21.1, 17q21.31, and 13q12.3-13.1, respectively. Twenty
six percent of studied cases manifested LOH for at least one marker in 15q14-21.1
exclusively. A significant correlation was found between LOH for studied region
and PSAD (prostate-specific antigen density). The findings suggest that RAD51 may
be considered as a prostate cancer susceptibility gene.
PMID- 26433960
TI - Adult survival selection in relation to multilocus heterozygosity and body size
in a tropical bird species, the Zenaida dove, Zenaida aurita.
AB - Both phenotypic and genetic quality can influence the survival of individuals
through time, although their relative influences are rarely addressed
simultaneously. Here we used capture-mark-recapture modelling to assess the
influence of both multilocus heterozygosity (MLH) and body size on apparent adult
survival in a tropical bird species, the Zenaida dove, Zenaida aurita, using a
sample of 391 individuals genotyped at 11 microsatellites, while controlling for
the effects of sex. No effect of body size on either adult survival or capture
rate was found. In the best model, survival was a logit linear function of MLH,
whereas detection probability was a sex-dependent logit linear function of the
logarithm of field effort, increasing with time and affected by a random
individual effect. Using a Bayesian approach, we found that MLH explained 1.14%
of the total deviance, as expected from theory and previous studies of
heterozygosity-fitness correlations, with no evidence for local effects. However,
results from capture-mark-recapture modelling indicated that expected longevity
varied from 4.8 years in the least heterozygous individuals (MLH = 0.37) to 10.6
years in the most heterozygous ones (MLH = 1), thus suggesting that MLH had
potentially a substantial effect on survival. We discuss our results in relation
to current hypotheses about the origin of heterozygosity-fitness correlations.
PMID- 26433959
TI - A phase I study of adjuvant intensity-modulated radiotherapy with concurrent
paclitaxel and cisplatin for cervical cancer patients with high risk factors.
AB - The aim of the study is to determine the maximum tolerated dose (MTD) and acute
dose-limiting toxicities (DLTs) of adjuvant concurrent paclitaxel and cisplatin
(TP) with pelvic intensity-modulated radiotherapy (IMRT) for early-stage cervical
cancer patients with high risk factors. Women who underwent radical hysterectomy
and pelvic lymphadenectomy for stages IB-IIA cervical cancer and had high risk
factors were enrolled. One cycle of TP was delivered before and after concurrent
chemoradiotherapy, respectively. Then 3 weeks after the start of the initial
cycle of the chemotherapy, patients received IMRT in a total dose of 50-50.4 Gy
in 25-28 fractions with two cycles of concurrent TP, which was administered with
escalating doses. Eighteen patients were enrolled at three dose levels. At dose
level 1 (paclitaxel 90 mg/m(2), cisplatin 40 mg/m(2)) and level 2 (paclitaxel 90
mg/m(2), cisplatin 50 mg/m(2)), DLT (grade 3 leukopenia) was observed in one
patient, respectively. At level 3 (paclitaxel 105 mg/m(2), cisplatin 50 mg/m(2)),
two DLTs (grade 3 leukopenia) were observed in two patients. The MTD of
paclitaxel and cisplatin was then defined as 90 and 50 mg/m(2), respectively.
Pelvic IMRT and concurrent TP is a safe and tolerable adjuvant treatment regimen
for cervical cancer patients with high risk factors. The MTD of concurrent
chemotherapy is paclitaxel 90 mg/m(2) and cisplatin 50 mg/m(2). Trial
registration Current controlled trials ChiECRCT-2014025.
PMID- 26433961
TI - Environmental drivers of carbon and nitrogen isotopic signatures in peatland
vascular plants along an altitude gradient.
AB - Peatlands are important sinks of atmospheric carbon (C) that, in response to
climate warming, are undergoing dynamic vegetation succession. Here we examined
the hypothesis that the uptake of nutrients by different plant growth forms
(PGFs) is one key mechanism driving changes in species abundance in peatlands.
Along an altitude gradient representing a natural climate experiment, we compared
the variability of the stable C isotope composition (delta(13)C) and stable
nitrogen (N) isotope composition (delta(15)N) in current-year leaves of two major
PGFs, i.e. ericoids and graminoids. The climate gradient was associated with a
gradient of vascular plant cover, which was parallelled by different
concentrations of organic and inorganic N as well as the fungal/bacterial ratio
in peat. In both PGFs the (13)C natural abundance showed a marginal spatial
decrease with altitude and a temporal decrease with progression of the growing
season. Our data highlight a primary physical control of foliar delta(13)C
signature, which is independent from the PGFs. Natural abundance of foliar (15)N
did not show any seasonal pattern and only in the ericoids showed depletion at
lower elevation. This decreasing delta(15)N pattern was primarily controlled by
the higher relative availability of organic versus inorganic N and, only for the
ericoids, by an increased proportion of fungi to bacteria in soil. Our space-for
time approach demonstrates that a change in abundance of PGFs is associated with
a different strategy of nutrient acquisition (i.e. transfer via mycorrhizal
symbiosis versus direct fine-root uptake), which could likely promote observed
and predicted dwarf shrub expansion under climate change.
PMID- 26433962
TI - Germline TERT promoter mutations are rare in familial melanoma.
AB - Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while
mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP,
POT1), have also been implicated in melanomagenesis. Mutation of the promoter of
the telomerase reverse transcriptase (TERT) gene (c.-57 T>G variant) has been
reported in one family. We tested for the TERT promoter variant in 675 multicase
families wild-type for the known high penetrance familial melanoma genes, 1863 UK
population-based melanoma cases and 529 controls. Germline lymphocyte telomere
length was estimated in carriers. The c.-57 T>G TERT promoter variant was
identified in one 7-case family with multiple primaries and early age of onset
(earliest, 15 years) but not among population cases or controls. One family
member had multiple primary melanomas, basal cell carcinomas and a bladder
tumour. The blood leukocyte telomere length of a carrier was similar to wild-type
cases. We provide evidence confirming that a rare promoter variant of TERT (c.-57
T>G) is associated with high penetrance, early onset melanoma and potentially
other cancers, and explains <1 % of UK melanoma multicase families. The
identification of POT1 and TERT germline mutations highlights the importance of
telomere integrity in melanoma biology.
PMID- 26433963
TI - Senescent peritoneal mesothelium induces a pro-angiogenic phenotype in ovarian
cancer cells in vitro and in a mouse xenograft model in vivo.
AB - It is believed that senescent cells contribute to the progression of primary and
metastatic tumors, however, the exact mechanisms of this activity remain elusive.
In this report we show that senescent human peritoneal mesothelial cells (HPMCs)
alter the secretory profile of ovarian cancer cells (A2780, OVCAR-3, SKOV-3) by
increasing the release of four angiogenic agents: CXCL1, CXCL8, HGF, and VEGF.
Proliferation and migration of endothelial cells subjected to conditioned medium
generated by: cancer cells modified by senescent HPMCs; cancer cells co-cultured
with senescent HPMCs; and by early-passage HPMCs from aged donors, were markedly
intensified. The same was the case for the vascularization, size and number of
tumors that developed in the mouse peritoneum upon injection of ovarian cancer
cells with senescent HPMCs. When the identified pro-angiogenic proteins were
neutralized in conditioned medium from the cancer cells, both aspects of
endothelial cell behavior intensified in vitro in response to senescent HPMCs
were markedly reduced. The search for mediators of senescent HPMC activity using
specific neutralizing antibodies and recombinant exogenous proteins showed that
the intensified angiogenic potential of cancer cells was elicited by IL-6 and TGF
beta1. At the transcriptional level, increased proliferation and migration of
endothelial cells exposed to cancer cells modified by senescent HPMCs was
regulated by HIF-1alpha, NF-kappaB/p50 and AP-1/c-Jun. Collectively, our findings
indicate that senescent HPMCs may promote the progression of ovarian cancer cells
by reprogramming their secretory phenotype towards increased production of pro
angiogenic agents and subsequent increase in the angiogenic capabilities of the
vascular endothelium.
PMID- 26433965
TI - Should a detailed ultrasound examination of the complete urinary tract be
routinely performed in women with suspected pelvic endometriosis?
AB - STUDY QUESTION: Is there any benefit to including the routine examination by
ultrasound of the bladder, ureters and kidneys of women with endometriosis?
SUMMARY ANSWER: The benefit of examination of the complete urinary tract of women
with suspected endometriosis is that ureteric endometriosis, with or without
hydronephrosis, can be detected which facilitates early intervention to prevent
nephropathy. WHAT IS ALREADY KNOWN: Women with endometriosis can get ureteric
obstruction but there is no clear consensus on the correct diagnostic technique.
Ultrasound is accurate at detecting women with bladder endometriosis but ureteric
involvement has not been assessed previously. STUDY DESIGN, SIZE, DURATION: This
was a prospective observational study, conducted at a teaching hospital over a
period of 14 months. A total of 848 women presenting with chronic pelvic pain
were included into the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women
with chronic pelvic pain underwent a detailed transvaginal and transabdominal
pelvic ultrasound examination to investigate possible causes of their symptoms.
This included a systematic assessment of the urinary bladder, pelvic sections of
the ureters and kidneys. The ultrasound findings were compared with findings at
surgery and the results of targeted urological imaging and interventions. MAIN
RESULTS AND THE ROLE OF CHANCE: A total of 848 women presenting with chronic
pelvic pain were included into the study. 28/848 women (3.3% 95% CI 2.1-4.5) had
evidence of urinary tract abnormalities on initial ultrasound scan. Among these
17/848 (2.0% 95% CI 1.06-2.94) had evidence of urinary tract endometriosis,
whilst 11/848 (1.3% 95% CI 0.54-2.06) women had other urinary tract
abnormalities. Among women with urinary tract endometriosis 11/17 (65%) had
evidence of ureteric involvement, 3/17 (18%) had both ureteric and bladder
disease and 3/17 (18%) had bladder disease only. 12/17 (59%) women with urinary
tract endometriosis also had evidence of hydronephrosis. The diagnosis of
ureteral endometriosis had a sensitivity of 12/13 (92%) (95% CI 63.9-99.8),
specificity 151/151 100% (95% CI 97.6-100), PPV 100% (95% CI 73.5-100), NPV 99.3%
(95% CI 96.3-99.9%) LR- 0.08 (95% CI 0.01-0.39). LIMITATIONS, REASONS FOR
CAUTION: The routine examination of the complete urinary tract including the
distal ureters is a novel technique that should be evaluated in different
populations. WIDER IMPLICATIONS OF THE FINDINGS: Ultrasound is an accurate test
to diagnose urinary tract involvement in women with suspected pelvic
endometriosis and examination of the complete urinary tract should become an
integral part of ultrasound assessment of women with suspected endometriosis.
PMID- 26433966
TI - Substrate preference of citrus naringenin rhamnosyltransferases and their
application to flavonoid glycoside production in fission yeast.
AB - Flavonoids, which comprise a large family of secondary plant metabolites, have
received increased attention in recent years due to their wide range of features
beneficial to human health. One of the most abundant flavonoid skeletons in
citrus species is the flavanone naringenin, which is accumulated as glycosides
containing terminal rhamnose (Rha) after serial glycosylation steps. The linkage
type of Rha residues is a determining factor in the bitterness of the citrus
fruit. Such Rha residues are attached by either an alpha1,2- or an alpha1,6
rhamnosyltransferase (1,2RhaT or 1,6RhaT). Although the genes encoding these
RhaTs from pummelo (Citrus maxima) and orange (Citrus sinensis) have been
functionally characterized, the details of the biochemical characterization,
including the substrate preference, remain elusive due to the lack of
availability of the UDP-Rha required as substrate. In this study, an efficient
UDP-Rha in vivo production system using the engineered fission yeast expressing
Arabidopsis thaliana rhamnose synthase 2 (AtRHM2) gene was constructed. The in
vitro RhaT assay using the constructed UDP-Rha revealed that recombinant RhaT
proteins (Cm1,2RhaT; Cs1,6RhaT; or Cm1,6RhaT), which were heterologously produced
in fission yeast, catalyzed the rhamnosyl transfer to naringenin-7-O-glucoside as
an acceptor. The substrate preference analysis showed that Cm1,2RhaT had glycosyl
transfer activity toward UDP-xylose as well as UDP-Rha. On the other hand,
Cs1,6RhaT and Cm1,6RhaT showed rhamnosyltransfer activity toward quercetin-3-O
glucoside in addition to naringenin-7-O-glucoside, indicating weak specificity
toward acceptor substrates. Finally, naringin and narirutin from naringenin-7-O
glucoside were produced using the engineered fission yeast expressing the AtRHM2
and the Cm1,2RhaT or the Cs1,6RhaT genes as a whole-cell-biocatalyst.
PMID- 26433964
TI - Long non-coding RNA CARLo-5 expression is associated with disease progression and
predicts outcome in hepatocellular carcinoma patients.
AB - Recently, many studies show that long non-coding RNAs (lncRNAs) play important
roles in cancer biology. Although its expression was reported dysregulated during
tumorigenesis, the contributions of lncRNAs to hepatocellular carcinoma (HCC) are
still largely unknown. In particular, the lncRNA CARLo-5 has a functional role in
cell-cycle regulation in colon cancer, while the clinical significance and
biological function of CARLo-5 in HCC remain unelucidated. In order to fill those
study blanks, the expression level of CARLo-5 in human HCC specimens was tested,
and its correlation with clinicopathologic features as well as the prognosis for
patients with HCC was analyzed. Additionally, MTT, wound healing and transwell
assays were employed to investigate the biological function of CARLo-5. The
results showed that CARLo-5 levels were significantly overexpressed in HCC
tissues compared to ANLT. Besides, high expression of CARLo-5 was associated with
liver cirrhosis (P = 0.001), tumor number (P < 0.001), vascular invasion (P =
0.001), capsular formation (P = 0.014) and Edmondson-Steiner grade (P < 0.001),
which proved that CARLo-5 was an independent risk factor for overall survival and
disease-free survival. In addition, in highly metastatic HCC cell lines (HCCLM3
and MHCC97-L), CARLo-5 was up-regulated, but in lowly metastatic HCC cell lines
(HepG2, SNU387), it showed down-regulated. Besides, by using gain and loss of
function experiments in HCC cell lines (HCCLM3 and HepG2), the results showed
that CARLo-5 overexpression significantly enhanced cell proliferation, migration
and invasion in vitro. Our study also revealed that CARLo-5 was prominently up
regulated in HCC specimens and its high expression was associated with poor
prognosis of HCC patients. Totally, those findings together indicate that CARLo-5
promotes proliferation and metastasis of HCC and potentially emerged as a novel
therapeutic target.
PMID- 26433967
TI - Metagenomic analysis of microbial community in uranium-contaminated soil.
AB - Uranium tailing is a serious pollution challenge for the environment. Based on
metagenomic sequencing analysis, we explored the functional and structural
diversity of the microbial community in six soil samples taken at different soil
depths from uranium-contaminated and uncontaminated areas. Kyoto Encyclopedia of
Genes and Genomes Orthology (KO) groups were obtained using a Basic Local
Alignment Search Tool search based on the universal protein resource database.
The KO-pathway network was then constructed using the selected KOs. Finally,
alpha and beta diversity analyses were performed to explore the differences in
soil bacterial diversity between the radioactive soil and uncontaminated soil. In
total, 30-68 million high-quality reads were obtained. Sequence assembly yielded
286,615 contigs; and these contigs mostly annotated to 1699 KOs. The KO
distributions were similar among the six soil samples. Moreover, the proportion
of the metabolism of other amino acids (e.g., beta-alanine, taurine, and
hypotaurine) and signal transduction was significantly lower in radioactive soil
than in uncontaminated soil, whereas the proportion of membrane transport and
carbohydrate metabolism was higher. Additionally, KOs were mostly enriched in ATP
binding cassette transporters and two-component systems. According to diversity
analyses, Actinobacteria and Proteobacteria were the dominant phyla in
radioactive and uncontaminated soil, and Robiginitalea, Microlunatus, and
Alicyclobacillus were the dominant genera in radioactive soil. Taken together,
these results demonstrate that soil microbial community, structure, and functions
show significant changes in uranium-contaminated soil. The dominant categories
such as Actinobacteria and Proteobacteria may be applied in environmental
governance for uranium-contaminated soil in southern China.
PMID- 26433968
TI - Responses of photosystems I and II of Acutodesmus obliquus to chemical stress
caused by the use of recycled nutrients.
AB - Nutrients derived from hydrothermal gasification of Acutodesmus obliquus were
tested on its biological compatibility to support growth of the same microalgae.
Photosynthetic parameters of photosystems I and II (PS I and PS II) were
investigated to study physiological effects on the microalgal cell. The nutrients
were collected as liquid residues. Dilutions of 1:500 showed no effect on both
photosystems. Lower dilutions affected PS II initially and later also PS I.
Cyclic electron flow around PS I compensated for loss of electrons due to
partially inhibited PS II. The highest tested concentration of liquid residue
erased any photosynthetic activity of PS II after 28 min and onwards. In
contrast, PS I remained active. The results suggest that PS I is less susceptible
than PS II and that the mixture of chemicals in the liquid residue did not
directly affect PS I but PS II. The toxicants in the residues seemed to interfere
with linear electron flow of PS II even though light-driven formation of radicals
and subsequent damage to one of the photosystems can be excluded as demonstrated
in darkness. Lowered photosynthetic activity of PS I during actinic irradiation
was caused due to lack of supply of electrons from PS II. The cyclic electron
flow might play a key role in delivering the energy needed to restore PS II
activity and to biodegrade the toxicants when linear electron flow failed. These
negative effects of liquid residue towards microalgal cells require a remediation
step for direct application of the liquid residue to substitute commercial
fertilizers in microalgal mass cultures.
PMID- 26433969
TI - Expression and immunogenic characterization of recombinant gp350 for developing a
subunit vaccine against Epstein-Barr virus.
AB - Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is linked to the
development of various malignancies. There is an urgent need for effective
vaccines against EBV. EBV envelope glycoprotein gp350 is an attractive candidate
for a prophylactic vaccine. This study was undertaken to produce the truncated
(codons 1-443) gp350 protein (gp350(1-443)) in Pichia pastoris and evaluate its
immunogenicity. The gp350(1-443) protein was expressed as a secretory protein
with an N-terminal His-tag in P. pastoris and purified through Ni-NTA
chromatography. Immunization with the recombinant gp350(1-443) could elicit high
levels of gp350(1-443)-specific antibodies in mice. Moreover, gp350(1-443)
immunized mice developed strong lymphoproliferative and Th1/Th2 cytokine
responses. Furthermore, the recombinant gp350(1-443) could stimulate CD4(+) and
CD8(+) T cell responses in vaccinated mice. Collectively, these findings
demonstrated that the yeast-expressed gp350(1-443) retained strong
immunogenicity. This study will provide a useful source for developing EBV
subunit vaccine candidates.
PMID- 26433970
TI - Enhanced D-lactic acid production from renewable resources using engineered
Lactobacillus plantarum.
AB - D-lactic acid is used as a monomer in the production of poly-D-lactic acid
(PDLA), which is used to form heat-resistant stereocomplex poly-lactic acid. To
produce cost-effective D-lactic acid by using all sugars derived from biomass
efficiently, xylose-assimilating genes encoding xylose isomerase and xylulokinase
were cloned into an L-lactate-deficient strain, Lactobacillus plantarum. The
resulting recombinant strain, namely L. plantarum NCIMB 8826 ?ldhL1-pLEM-xylAB,
was able to produce D-lactic acid (at optical purity >99 %) from xylose at a
yield of 0.53 g g(-1). Simultaneous utilization of glucose and xylose to produce
D-lactic acid was also achieved by this strain, and 47.2 g L(-1) of D-lactic acid
was produced from 37.5 g L(-1) glucose and 19.7 g L(-1) xylose. Corn stover and
soybean meal extract (SBME) were evaluated as cost-effective medium components
for D-lactic acid production. Optimization of medium composition using response
surface methodology resulted in 30 % reduction in enzyme loading and 70 %
reduction in peptone concentration. In addition, we successfully demonstrated D
lactic acid fermentation from corn stover and SBME in a fed-batch fermentation,
which yielded 61.4 g L(-1) D-lactic acid with an overall yield of 0.77 g g(-1).
All these approaches are geared to attaining high D-lactic acid production from
biomass sugars to produce low-cost, highly thermostable biodegradable plastics.
PMID- 26433971
TI - Comparing the efficacy and neuroinflammatory potential of three anti-abeta
antibodies.
AB - Immunotherapy is a promising strategy for the treatment of Alzheimer's disease
(AD). Antibodies directed against Amyloid Beta (Abeta) are able to successfully
clear plaques and reverse cognitive deficits in mouse models. Excitement towards
this approach has been tempered by high profile failures in the clinic, one key
issue has been the development of inflammatory side effects in the brain (ARIAs).
New antibodies are entering the clinic for Alzheimer's disease; therefore, it is
important to learn all we can from the current generation. In this study, we
directly compared 3 clinical candidates in the same pre-clinical model, with the
same effector function, for their ability to clear plaques and induce
inflammation in the brain. We produced murine versions of the antibodies:
Bapineuzumab (3D6), Crenezumab (mC2) and Gantenerumab (chGantenerumab) with an
IgG2a constant region. 18-month transgenic APP mice (Tg2576) were injected
bilaterally into the hippocampus with 2 ug of each antibody or control. After 7
days, the mice tissue was analysed for clearance of plaques and neuroinflammation
by histology and biochemical analysis. 3D6 was the best binder to plaques and in
vitro, whilst mC2 bound the least strongly. This translated into 3D6 effectively
clearing plaques and reducing the levels of insoluble Abeta, whilst
chGantenerumab and mC2 did not. 3D6 caused a significant increase in the levels
of pro-inflammatory cytokines IL-1beta and TNFalpha, and an associated increase
in microglial expression of CD11B and CD68. chGantenerumab increased pro
inflammatory cytokines and microglial activation, but minimal changes in CD68, as
an indicator of phagocytosis. Injection of mC2 did not cause any significant
inflammatory changes. Our results demonstrate that the ability of an antibody to
clear plaques and induce inflammation is dependent on the epitope and affinity of
the antibody.
PMID- 26433972
TI - Evidence and Counterevidence in Motion Perception.
AB - Sensory neurons gather evidence in favor of the specific stimuli to which they
are tuned, but they could improve their sensitivity by also taking
counterevidence into account. The Bours-Lankheet model for motion detection uses
counterevidence that relies on a specific combination of the ON and OFF channels
in the early visual system. Specifically, the model detects pairs of flashes that
occur separated in space and time. If the flashes have the same contrast
polarity, they are interpreted as evidence in favor of the corresponding motion.
But if they have opposite contrasts, they are interpreted as evidence against it.
This mechanism provides an explanation for reverse-phi (the perceived reversal of
an apparent motion stimulus due to periodic contrast-inversions) that is a
conceptual departure from the standard explanations of the effect. Here, we
investigate this counterevidence mechanism by measuring directional tuning curves
of neurons in the primary visual and middle temporal cortex areas of awake,
behaving macaques using constant-contrast and inverting-contrast moving dot
stimuli. Our electrophysiological data support the Bours-Lankheet model and
suggest that the counterevidence computation occurs at an early stage of neural
processing not captured by the standard models.
PMID- 26433973
TI - Risk factors and consequences of anastomotic leakage after Ivor Lewis
oesophagectomy?.
AB - OBJECTIVES: Oesophageal carcinoma (EC) remains an aggressive disease. Despite
extensive changes in therapeutic modalities, surgical resection remains the first
choice therapy for curable oesophageal cancer patients. Anastomotic sites are
prone to serious complications such as leakage, fistula, bleeding and stricture.
Leakage of the anastomosis (AL) remains one of the main causes of postoperative
morbidity and mortality. The purpose of this study was to identify predictors
associated with postoperative leakage after Ivor Lewis oesophagectomy and its
consequences in a single centre. METHODS: We performed a retrospective analysis
of 412 Ivor Lewis oesophageal resections in a single institute between 2005 and
2014. Univariable and multivariable logistic regression have been used to
identify predictors of AL and its impact on postoperative outcome and overall
survival. Kaplan-Meier curve was used to analyse overall survival and log-rank
analysis to determine odds ratio. RESULTS: A total of 412 patients were
evaluated. Mean age was 62 +/- 11 years (77% male). Overall leak rate was 2.9%.
In-hospital or 30-day mortality was 4.4%. Mean intensive care unit (ICU) stay was
1 day and mean hospital stay was 19 days. A history of renal failure, diabetes,
higher American Society of Anaesthesiologists score and current cigarette and
corticosteroid use were identified as predictors of AL on univariable analysis.
Multivariable analysis identified active smoking [P = 0.05, odds ratio (OR) 4.34,
95% confidence interval (CI): 0.98-19.28] and active corticosteroid use (P <
0.001, OR 15.8, 95% CI: 3.25-76.7) as independent significant predictors. A
history of diabetes tended to be associated with a higher leakage rate but failed
to reach statistical significance. AL was associated with a longer ICU and
hospital stay and a significantly higher mortality (42% in the AL group vs 3% in
the control group, P < 0.0001). CONCLUSIONS: Anastomotic leakage after
oesophagectomy is a major cause of postoperative morbidity and mortality.
Identifying risk factors preoperatively can contribute to the prevention of
postoperative complications.
PMID- 26433974
TI - Is a minimally invasive approach for mitral valve surgery more cost-effective
than median sternotomy?
AB - A best evidence topic in cardiac surgery was written according to a structured
protocol. The question addressed was: is a minimally invasive approach for mitral
valve surgery more cost-effective than median sternotomy? Altogether, 51 studies
were found using the reported search, of which 7 represented the best evidence to
answer the clinical question. The authors, journal, date and country of
publication, patient group studied, study type, relevant outcomes and results of
these papers were tabulated. No randomized controlled trials have assessed the
cost-effectiveness of less invasive mitral valve surgery compared with median
sternotomy, with the best evidence coming from retrospective and propensity
matched analyses. Five studies compared minithoracotomy versus sternotomy, one
compared minimally invasive port-access surgery versus sternotomy and one
compared video-assisted minithoracotomy versus sternotomy. The use of a
minithoracotomy or a minimally invasive port-access approach for mitral valve
surgery resulted in significant reductions in costs of cardiac imaging and
laboratory tests, lower use of blood products, fewer perioperative infections,
faster recovery, shorter hospital length of stay, fewer requirements for
rehabilitation and lower readmission rates in the following postoperative year.
We conclude that a minimally invasive approach for mitral valve surgery is safe,
effective and significantly more cost-effective than median sternotomy.
PMID- 26433975
TI - POLICY AND PROCEDURE CONSIDERATIONS FOR HEALTH INFORMATION EXCHANGE
ORGANIZATIONS.
PMID- 26433977
TI - Catherine Smrcina, PhD, RN, ONC: 1952-2015.
PMID- 26433976
TI - [Update on Current Care Guidelines. Rheumatoid Arthritis (RA)].
AB - Patients with signs and symptoms of early rheumatoid arthritis (RA) should be
referred to a multidisciplinary rheumatology clinic. The ACR-EULAR criteria help
in identification of patients with risk for erosive RA. Treatment should aim at
early remission. Start with the combination of methotrexate, hydroxychloroquine,
sulfasalazine, and low-dose glucocorticoid is recommended if contraindications
exist. Methotrexate has better bioavailability as injection. Glucocorticoids are
injected into active joints. Patient education with shared decision is essential.
Exercise training is recommended. If treatment target is not achieved by the
DMARD combination, a biological drug is added.
PMID- 26433978
TI - Opinion Paper: Post-surgical Delirium, Consciousness, and Therapy.
PMID- 26433979
TI - Cholera, 2014.
PMID- 26433980
TI - Revitalizing control efforts for cholera.
PMID- 26433981
TI - Innovative WASH interventions to prevent cholera.
PMID- 26433982
TI - Cholera surveillance, rapid diagnostics and laboratory networks.
PMID- 26433983
TI - Cholera in Bangladesh.
PMID- 26433984
TI - Cholera in Haiti: successes and challenges in a low income country.
PMID- 26433985
TI - Editorial note: cholera a public health priority.
PMID- 26433989
TI - MouthHealthy--Increasing the Public's Oral Health Literacy.
PMID- 26433988
TI - A Time For Every Purpose.
PMID- 26433990
TI - Missing a Mentor.
PMID- 26433991
TI - Outreach, Prevention, and the "Urgent Chair".
PMID- 26433992
TI - The Pain Puzzle: Q's, A's, and Mapping the Maze.
PMID- 26433993
TI - Differential Diagnoses for Persistent Pain Following Root Canal Treatment: A
Study in the National Dental PBRN.
AB - INTRODUCTION: Pain present six months following root canal treatment (RCT) may be
either of odontogenic or non-odontogenic origin. This is important because
treatments and prognoses are different; therefore, the aim of this study was to
provide specific diagnoses of patients reporting pain six months after receiving
initial orthograde RCT. METHODS: We enrolled patients from the Midwest region of
an existing prospective observational study of pain after RCT. Pain at six months
was defined as >= 1 day of pain and average pain intensity of at least 1/10 over
the preceding month. An endodontist and an orofacial pain practitioner
independently performed clinical evaluations, which included periapical and cone
beam computed tomograph (CT) radiographs, to determine diagnoses. RESULTS: Thirty
eight out of the 354 eligible patients in the geographic area (11%) met the pain
criteria, with 19 (50%) consenting to be clinically evaluated. As the sole reason
for pain, 7 patients (37%) were given odontogenic diagnoses (4 involving the RCT
tooth, 3 involving an adjacent tooth). Eight patients (42%) were given non
odontogenic pain diagnoses (7 from referred temporomandibular disorder [TMD]
pain, 1 from persistent dentoalveolar pain disorder [PDAP]). Two patients (11%)
had both odontogenic and non-odontogenic diagnoses, while 2 (11%) no longer fit
the pain criteria at the time of the clinical evaluation. CONCLUSION: Patients
reporting "tooth" pain 6 months following RCT had a non-odontogenic pain
diagnosis accounting for some of this pain, with TMD being the most frequent non
odontogenic diagnosis. Dentists should have the necessary knowledge to
differentiate between these diagnoses to adequately manage their patients.
PMID- 26433995
TI - I Have Something to Say--But No One Is Listening!
PMID- 26433994
TI - Improve Your Practice and Engage Your Patients: Participate in the NDPBRN.
PMID- 26433997
TI - The Future of Dental Board Structure and Regulation.
PMID- 26433998
TI - President's Address.
PMID- 26433999
TI - Amelogenesis Imperfecta, Facial Esthetics and Snap-On Smile.
AB - Amelogenesis imperfecta is a hereditary enamel protein disorder affecting
deciduous and secondary crown formation. The prevalence ranges from 1:700 to
1:14,000 depending on the population. These teeth may be hypoplastic,
hypomineralized, or hypermineralized and are often discolored, sensitive and
caries vulnerable. Patients often present with psychosocial issues due to
appearance. Primary teeth are often treated with stainless steel crowns while
secondary teeth are treated with full coverage esthetic crowns. The presenting
preteen male here was fitted with Snap-On Smile? (www.snaponsmile.com). This
treatment option provided cosmetic enhancement of the patient's appearance
besides stabilization without altering the primary and secondary dentition during
adolescent development.
PMID- 26434000
TI - Oral Complications of Cancer Therapy: A Summary Guide for the Clinician.
AB - Oral complications of cancer therapy can be so severe that they can lead to the
discontinuation of cancer treatment. This can affect prognosis, patient survival,
and alter patient quality of life. Early recognition and management of oral
complications in cancer patients is a very important part of the overall
treatment. Currently, a large number of cancers are treated at the ambulatory
level, and when patients develop oral problems they may seek care from their
private dentist. The goal of this manuscript is to discuss common oral
complications of cancer therapy, and the role the general dentist can play in
diagnosis and management.
PMID- 26434001
TI - Combination PROP: A Case Report of a Hybrid Flexible and Traditional Partial
Removable Dental Prosthesis.
AB - The need for partial removable dental prostheses (PRDP) is increasing as the over
65 partially edentulous population grows. The use of flexible materials in the
fabrication of these prostheses has captured a large portion of the market once
occupied by traditional cast metal PRDPs. While there are some clinical
advantages to the use of flexible PRDPs, there are also disadvantages and
contraindications that must be considered. This paper describes a clinical case
in which a patient's dentition is restored with a hybrid partial removable dental
prosthesis consisting of a traditional metal framework and flexible denture base
and clasps. This design can result in achieving the benefits of each type of
prosthesis in an effort to satisfy the needs of the patient.
PMID- 26434002
TI - Seeking to Understand the Reader of Interest-Your Patient-Health Literacy and
Adherence Concerns for the Dentist and the Dental/Medical Team.
AB - The overall health of the United States' (U.S.) population has been surveyed and
reported for several decades in a quest by healthcare professionals to understand
the etiology for healthcare disparities and seek to lessen its effects on
individuals and, ultimately, eliminate them. Many of these surveys and reports
have illuminated disparities, of access to healthcare by focusing on measures to
address health literacy deficiencies. A plethora of information concerning
patients' health literacy skills and printed information has been made available
for dentists and their staff. The printed information is in the format of
published patient- centered educational guidelines and readable dental and
medical limited reach media (LRM), such as information sheets and prescription
drug leaflets. LRM has great potential to enhance access to healthcare
information for the reader of interest--your patient--at a readable and
comprehensible level. Printed materials are an effective means to enhance health
promotion and education for the lay populace. Tailored LRM protocol and the
Patient Introduction Form (PIF) are excellent educational instruments for
dentists and the dental/medical team (The Team). These instruments are valuable
assets for The Team to assist its patients in monitoring and maintaining dental
and medical adherence protocols in their daily lives.
PMID- 26434004
TI - Health, Growth and Development, and Kinesiology.
PMID- 26434003
TI - Changes in the Clinical Training of Dental Students at the University of
Tennessee College of Dentistry.
AB - Dental education is an ever evolving process due to continual advancements in
patient treatment. This article provides the reader with a look into an
educational process that affords the student with better clinical experience
without an increase in clinical training hours. When a comprehensive care model
of education is introduced into a traditional care setting, the comparison of
procedures completed with the previous 5 years results indicate an increase in
the number of amalgam and composite restorations placed of 26% and an increase in
crowns placed of 32.9%. Integration of the dental hygiene program and additional
remote sites afford new populations of patients where clinical skills can be
developed which will result in a graduate more able to go directly into private
practice.
PMID- 26434005
TI - Trend of Growth and Level of Nutrition in Children from 7 to 14 Years.
AB - The research was conducted with the aim of determining the trend of development
of morphological characteristics in female and male students aged seven (7) to
fourteen (14) years. The sample of examinees was drawn from the population of
female and male students from first (1) to eighth (8) grade of elementary schools
in Split. In total, 771 female students and 840 male students were measured.
Height, weight and upper arm and dorsal skin folds were measured, and used in
calculation of fat tissue percentage. The results indicate the increase of body
height and mass, what is in concordance with the secular trend. The increased
percentage of fat tissue, especially in first four grades of elementary school,
is a characteristic of this population, especially boys. The characteristic of
this population is obesity, caused by the inadequate nutrition and lack of
kinesiological activity. In later age, the trend of height growth and gaining
weight continues, but the weight increase occurs due to fat tissue increase, not
increase of muscle tissue.
PMID- 26434006
TI - Correlation between Balance Ability and Speech-Language Development in Children.
AB - The longitudinal study was conducted in order to establish whether the success
rate of reflexes related to maintaining balance at birth is in correlation with
the success rate of maintaining balance in early childhood, as well as to examine
the correlation of a certain level of speech and language development with the
ability of maintaining balance at birth and at the age of 5. The main study group
included 54 children of both genders, aged 5.0 to 5.4, whose balance ability and
speech and language status were evaluated based on the battery of standardized
tests, whereas the group of reflexes related to the function of the vestibular
sense was clinically tested on the 3rd day upon birth, within the same sample of
children. The data at birth and at the age of 5 were recorded by means of a
digital camera, then scored and statistically and descriptively processed. The
research results indicated a statistically significant correlation between the
achieved level of balance ability in the newborns and five-year-olds, as well as
between balance skills and a certain level of speech and language development in
children at the age of 5. The importance of this research lies in new knowledge
in the domain of maturation of vestubular function immediately after birth, given
that this segment of physiology of a newborn has not so far been processed in
such a way, as well as in the recognition of function of the vestibular sense as
another parametre of a child's maturation.
PMID- 26434007
TI - The Percentage of Body Fat in Children and the Level of their Motor Skills.
AB - The aim of this study was to determine the prevalence of overweight and obesity
among primary education pupils and to identify differences in motor skills
between normal weight, excessive and obese pupils. Partial aim was to determine
differences in motor status of girls and boys and their anthropometric
characteristics (Body Mass Index, body fat percentage). The study was conducted
in two primary schools in Zagreb, Ivan Goran Kovacic and Davorin Trstenjak. Total
of 333 pupils, aged 7-11, were measured (178 boys and 155 girls). Four
anthropometric and seven motor variables were used to analyze differences in
motor abilities of children. Children were divided into three groups within
gender based on their body fat measures. We established a statistically
significant difference in motor abilities between groups of subjects in three
subsamples (1st-2nd class girls and 3rd-4th boys and girls). Children with normal
weight have better results in explosive strength, coordination, static strength
of arm and shoulder than children who are overweight and obese. The differences
are not observed in motor variables where body weight is not a requisite for
efficient execution of movement. Differences in motor skills by gender showed
that boys are better in coordination, speed of the simple movements, explosive
and repetitive strength, and girls are better in flexibility. The conclusion of
this study confirmed the existence of differences in the development of motor
skills in children with normal body weight compared to children who are
overweight or obese. These facts prove that excessive body weight has negative
repercussions on motor performance.
PMID- 26434008
TI - Effects of Acute Physical Exercise on Mathematical Computation Depending on the
Parts of the Training in Young Children.
AB - The aim of this study was to determine whether acute physical exercise may
increase the ability to quickly solve basic mathematical operations in young
children. In this way, the children acquired the means to activate a larger area
of the brain when necessary. The research sample of 38 preschool and 18
schoolchildren was tested in basic mathematical operations before and after
physical exercise. The results showed that children's computational performance
was enhanced significantly during exercise and remained stable after relaxation
part of their physical training.
PMID- 26434009
TI - Can Kinesiological Activities Change "Pure" Motor Development in Preschool
Children during One School Year?
AB - The purpose of this study was to evaluate the effects of an additional,
organized, and more intensive kinesiological treatment on "pure" motor abilities
in preschool children. In the present study an experimental treatment was carried
out on a sample of 37 preschool boys by applying kinesiological activities. The
60 minute treatment was applied over a period of one school year (9 months),
twice a week. A control group of 31 boys were trained according to the regular
program for preschool institutions. Treatment effects were assessed by 8 motor
ability tests and 5 anthropometric measures. The significant differences between
the groups, which were observed after the final measurement and compared to the
initial one, proved that the kinesiological treatment had a positive impact on
the general development of "pure" motor abilities. The most significant effect of
experimental kinesiological treatment was the improvement in whole body force,
flexibility and coordination of preschool boys. These findings, obtained only in
one school year, point to the importance of physical exercise and the application
of additional kinesiological activities with various modalities, to improve motor
development, even morphological growth and development in preschool children. The
effects of the perennial application of kinesiological activities, under the
supervision of kinesiological professionals, could be beneficial and could form
the basis for a better biological and motor development in older age.
PMID- 26434010
TI - Differences in Some Kinematic Parameters between Two Qualitatively Different
Groups of Pole Vaulters.
AB - The basic aim of this research was to determine the differences of kinematic
parameters in two qualitatively different groups of young pole vaulters. With
this purpose, a research was conducted in which the video records from a
competition were acquired. The sample of entities (N = 71) consisted of
successful vaults of 30 pole vaulters, whose attempts were recorded at the
European Junior Championship in Novi Sad, held on 23-26th July 2009. The
examinees performed the vaults as a part of the elimination competition for the
finals, and during the final part of the competition. The age of examinees was
from 17 to 19 years, and the span of their best results was from 4.70 to 5.30
meters. The kinematic analysis was conducted according to the standards of APAS
procedure (Ariel Performance Analysis System, USA), determining 25 kinematic
variables necessary for further analysis. The entities (vaults) were divided into
two categories (qualitative classes) based on the expert knowledge. Group 1
consisted of successful vaults up to 4.90 m (N = 46), while group 2 consisted of
successful vaults whose height was more than 4.90 m (N = 25). The discrimination
analysis determined the parameters differentiating the vaults of different
quantitative classes. Also, it was confirmed that the result efficiency in pole
vault was primarily determined by the variables defined by motor abilities, as
well as the indicators determining the vault performance technique.
PMID- 26434011
TI - Relation between Anthropometric Characteristics and Kinematic Parameters which
Influence Standing Long Jump Efficiency in Boys and Adolescents.
AB - The aim of this research was to determine the relation between the
anthropometrical variables and kinematic parameters that influence the standing
long jump efficiency in boys and adolescents aged 4 to 18, as well as students of
second year of Faculty of Kinesiology. With this aim, a sample of 120 examinees
has been selected and divided into 5 experimental groups consisting of 20 boys
and adolescents (aged 4 to 6, 7 to 9, 10 to 12, 13 to 15, 16 to 18), and one
control group consisting of 20 second year students of Faculty of Kinesiology.
The sample of variables consisted of 21 kinematic parameters relevant for
efficient standing long jump performance, followed by battery of 13 morphological
characteristics, as well as the age of the examinees. This research determined
the relation between certain morphological characteristics and kinematic
parameters relevant for standing long jump performance. It can be concluded that
in adults, the jump length was primarily influenced by body mass, subcutaneous
fat tissue and body fat percentage, while in younger age groups, besides the
mentioned measures, the examinees who were taller, had longer arms and legs
achieved better results.
PMID- 26434013
TI - The Relationship between 200 m Performance and Selected Anthropometric Variables
and Motor Abilities in Male Sprinters.
AB - The goal of this study was the investigation of the relationship between 200 m
performance and motor abilities and anthropometric characteristics of different
level of male sprinters (200 m performance 23.80 +/- 2.16 s--the best results
21.40 s). The physical fitness measures included: 50 m from standing and flying
start, standing long jump (SLJ) standing five jump (SFJ), double and single leg
countermovement jumps CMJ), flexibility (sit and reach) and 4 kg shot put
throwing (over head). The Spearman correlation coefficient was applied to verify
the association. The results demonstrated strong relationships (p < 0.05) between
200 m performance and experience (age) and body mass (r = 0.85, r = -0.80
respectively) As for the motor abilities strong relationship exists between 200 m
and time of 150 m, 50 m from standing and flying start and CMJ on single leg.
Vertical jumping displayed stronger relationship with 200 m performance that
horizontal one. From a practical point of view this is very important notice.
PMID- 26434012
TI - The Influence of Anthropometric Characteristics on Kinematic Parameters of
Children's Sprinter's Running.
AB - Children's sprinters running differs from the adults' one primarily in their
motoric abilities, anthropometric characteristics, physiological and biochemical
characteristics, as well as psychological and sociological characteristics. This
research's aim was to examine the influence of anthropometric characteristics on
kinematic parameters of children's sprinter's running. The sample of variables
consisted of variables which determine anthropometric characteristics (14
anthropometric characteristics) and of 5 kinematic parameters'variables of
sprinter's running. Kinematic parameters of sprinter's running in the phase of
maximal speed have been collected by applying the Optojump technology (Microgate,
Italy) and the sprinter's running times were measured every 5 meters on a 50 m
lap. The results obtained from the multiple regression analysis between the group
of anthropometric characteristics and the 50 m running results indicate that the
percentage of fatty tissue is a statistically significant variable with boys,
while the same variable with girls is near the limit of statistical significance.
In the factor structure of anthropometric characteristics two factors have been
set apart with boys and three with girls. The first factor set apart with both
boys and girls is the factor of body voluminosity, the second factor with boys is
the factor of longitudinal dimensionality, while with girls it is the factor of
fatty tissue quantity. The factor of longitudinal dimensionality is the third
girls' factor. For most variables a negative correlation has been determined with
a higher percentage of fat or a higher quantity of subcutaneous fatty tissue with
both boys and girls. Boys having a lower quantity of subcutaneous fatty tissue
achieve better results in 50 m running, they have a shorter duration of contact
with the pad, a longer duration of the flight phase and a longer step length when
compared to boys with a higher quantity of subcutaneous fatty tissue. Boys with a
bigger body muscular mass achieve a shorter duration of the contact, a longer
duration of the flight and a longer step length. Girls who have a lower quantity
of subcutaneous fatty tissue achieve a better 50 m running time, have a shorter
duration of contact with the pad and a longer step length. It has been
established that taller boys have a longer step length, and longer feet
significantly influence the longer duration of contact with the pad and the
lowering of the step frequency.
PMID- 26434014
TI - Success in Adopting Technique of Alpine Skiing with Respect to Motor Abilities of
the Children Aged 7-8 Years.
AB - The aim of this research was to determine relations between estimated motor
abilities and efficiency of alpine ski learning in children ski beginners. It
included 54 children between 7 and 8 years of age (average 7.44 +/- 0.52 years).
Children were tested for balance, agility, strength, coordination and frequency
of movement on ten motor ability tests. After motor abilities were assessed,
participants learned alpine skiing during six-day alpine ski school and upon
completion of ski school program, were tested on three elements of alpine ski
technique (stopping in a snow-plough, uphill turn and turns around the posted
marks) by three independent judges. According to achieved level of ski knowledge,
they were allocated to three groups differing by the level of success; less
successful (N = 18; 26-44 points), moderately successful (N = 11; 45-48 points)
and successful (N = 25; 49-55 points). Significant differences in success of
adopting basic ski technique were noticed with respect to the results achieved in
the task polygon backwards (F = 6.162, p = 0.004), foot tapping (F = 6.337, p =
0.003) and crossed arm sit-ups (F = 3.099, p = 0.053). The participants who
successfully adopted the basic ski technique also achieved good results in tests:
polygon backwards, foot tapping, crossed arm sit-ups, side steps, balancing on
left leg perpendicular on balance board, vertical jump and medium results in
tests 20m dash and balancing on right leg perpendicular on balance board. Our
results suggest that successful participants have better developed coordination,
frequency of movement, strength and agility.
PMID- 26434015
TI - Gender Differentiations of Some Anthropological Characteristics of Karate Players
-Cadets.
AB - The research was conducted with the aim of determining gender differentiations of
some anthropological characteristics of male and female cadet karate players. To
achieve this aim, a group of 10 morphological variables, ten motor tests, five
situation motor test and six technical performance evaluation tests was applied.
Two hundred and six competing players were measured, of which 105 male and 101
female. The examinees were divided according to weight categories (lower and
higher weight categories). Based on the variance analysis and canon
discrimination analysis a conclusion can be made: gender differentiations are
most strongly expressed in morphological and basic motor area, and significantly
less in the area of specific motor abilities and motor knowledge (technical
efficiency).
PMID- 26434016
TI - Technical and Tactical Aspects that Differentiate Winning and Losing Performances
in Elite Male Karate Fighters.
AB - The purpose of this research was to identify the fighters' technical and tactical
activity indicators in order to determine indicator significance regarding
situational efficiency and designation between winning and losing performances in
a karate match. We scientifically observed a sample of 274 male contesters of 137
karate matches during the 2008 World Karate Championship in Tokyo. Each
individual competitor was observed in maximum of three matches. The matches were
recorded using a DVD camera in order to collect data for further analysis, and
the sample was further described using 48 technical and tactical indicators of
situational efficiency and match outcome variables. The obtained results indicate
that a karate match is composed of 91% of non-scoring techniques and 9% of
scoring techniques in the total technique frequency. On this basis a significant
difference in the situational efficiency between the match winners and the losing
contesters has been discovered. Those two groups of fighters exhibit a
statistically significant difference (p<0.05) in 11 out of 21 observed variables
of situational efficiency in the table of derived situational indicators. A
prevalence of non-scoring techniques suggests that energy demand and technical
and tactical requirements of a karate match are in the largest extent defined by
non-scoring techniques. Therefore, it would be a grave mistake to disregard non
scoring karate techniques in any future situational efficiency studies. It has
been discovered that the winners differ from the defeated contesters by a higher
level of situational efficiency in their executed techniques, which incorporate
versatility, biomechanical and structural complexity, topological diversity and a
specific tactical concept of technique use in the attack phase.
PMID- 26434017
TI - Importance of Hierarchical Structure Determining Tennis Performance for Modern
Defensive Baseliner.
AB - Hierarchies are present everywhere (physics, medicine, nature, human needs, etc.)
and tennis is no exception. Is counterpuncher's goal just to chase down every
ball and force the opponents into long rallies? The aim of this first empirical
study is integrate theory and practice about overall quality evaluation and
accurately analyze offensive and defensive tennis priorities for counterpunchers.
Weight of each criterion was obtained using AHP technique in Expert Choice
software. The results indicate that this model is able to provide important
training variables in order to control and manipulate training process. Also,
issues prior to research indicate that sports scientists and expert coaches need
to learn from each other in order to help players maximizing their performance.
PMID- 26434018
TI - Relationship of Speed, Agility, Neuromuscular Power, and Selected
Anthropometrical Variables and Performance Results of Male and Female Junior
Tennis Players.
AB - The aim of the study was to analyses the relation between the selected speed,
agility, and neuromuscular power test items. The sample of subjects consisted of
154 male and 152 female young tennis players. Using six motor and three
anthropometrical tests we investigate differences between males and females and
between two age categories. Finally, we analyzed the relation between motor and
anthropometrical tests and a player's tennis performance. The correlation between
the two agility test items and 5-m sprint is very large in male players, while
only moderate with 20-m sprint in female category. Male tennis players have
higher correlations between speed test items and neuromuscular test items. The
speed test item (5-m sprint) has large correlation with a player's tennis
performance. One-way analysis of variance results indicated that young male
tennis players performed significantly better than females in all motor test
items. Significant differences between genders have not been revealed only in the
body mass index. Differences between the males aged 18& under and 16& under have
been noted as significant in all test items, except the vertical jump, while
differences between the females have been noted as significant in three
anthropometrical tests, quarter jump, and the fan-drill test. Regression analyses
have shown that the system of prediction variables explains a relatively small
part of variance (46%--males and 40%--females). In both genders, it has been
revealed that test items measuring speed significantly influence a player's
tennis performance.
PMID- 26434019
TI - Non-Linear Approach in Kinesiology Should Be Preferred to the Linear--A Case of
Basketball.
AB - In kinesiology, medicine, biology and psychology, in which research focus is on
dynamical self-organized systems, complex connections exist between variables.
Non-linear nature of complex systems has been discussed and explained by the
example of non-linear anthropometric predictors of performance in basketball.
Previous studies interpreted relations between anthropometric features and
measures of effectiveness in basketball by (a) using linear correlation models,
and by (b) including all basketball athletes in the same sample of participants
regardless of their playing position. In this paper the significance and
character of linear and non-linear relations between simple anthropometric
predictors (AP) and performance criteria consisting of situation-related measures
of effectiveness (SE) in basketball were determined and evaluated. The sample of
participants consisted of top-level junior basketball players divided in three
groups according to their playing time (8 minutes and more per game) and playing
position: guards (N = 42), forwards (N = 26) and centers (N = 40). Linear
(general model) and non-linear (general model) regression models were calculated
simultaneously and separately for each group. The conclusion is viable: non
linear regressions are frequently superior to linear correlations when
interpreting actual association logic among research variables.
PMID- 26434020
TI - Differences in Basic Non-Standard Situational Efficiency Indicators between
Winning and Defeated European Senior Basketball Teams.
AB - The aim of the conducted research was to identify and explain the differences in
basic non-standard situational efficiency indicators between winning and defeated
European senior basketball teams. Discriminant analysis and Mann-Whitney U-test
were used with the purpose of investigating the differences between winning and
defeated teams in the domain of basic non-standard situational variables. The
grouping variable distinguished 24 defeated teams from 24 winning teams
participating in 2009/2010 season of Euroleague Top 16. The research clearly
reveals the differences between the winning and defeated European senior
basketball teams in the domain of non-standard situational variables of position
and transition offense and defense. Eight situational efficiency indicators were
used which include the overall number of successful and unsuccessful position and
transition defenses and offenses. Based on the results obtained by parametric and
non-parametric methods, it has been noticed that successful position defense is
crucial for winning, and unsuccessful position offense is an indicator of defeat
prediction. Therefore, practical aims in situational training must involve
balanced development of relevant abilities and skills which determine successful
simultaneous performance of multiple tasks in all the phases of game flow. Such
process of sport preparation improves the overall actual quality of players and
whole team performance. In conclusion, it is important to emphasize that the
process of improving position and transition defense stimulates the development
of position and transition offense, and vice versa.
PMID- 26434021
TI - Morphological Profiles of Playing Positions in Defense and Offense in
Professional Men's Handball.
AB - The main scope of the study is concerned with the morphological profiles of
playing positions in defense, offense and the combinations of these two phases of
the game. Furthermore, study attempted to identify the difference between the
morphological profiles of the individual playing positions. Entity sample of the
study consist of the 148 players that participated in 45 matches of the World
Men's Handball Championship which took place in Croatia in 2009. The study dealt
with the differences between playing positions concerning basic morphological
characteristics which are due to the selection based on roles and tasks that need
to be carried out in each position. Moreover, morphological similarity of playing
positions in offense and defense was noticed. It was determined that wing players
play dominantly in the position of left back, external players in the position of
right and center back whereas pivots participate in the positions of center, back
and center forward positions in defense. Morphological profiles of playing
positions in defense, offense and in the combination of these two phases of the
game were determined. Identical positions on different sides in offense (left
right wing player, left-right back player) have shown that these positions are
quite similar when it comes to morphological profile and playing position in
defense. It can be concluded that some playing positions in offense are
accompanied by the respective positions in defense. All positions are
characterized by one or two morphological profiles.
PMID- 26434023
TI - An Explanation of the Influence on Deciding which Type of Foot Strike to Use when
Running Barefoot or in Minimalistic Shoes.
AB - Buying minimalistic shoes does not mean that you know how to use them.
Salespersons are rarely competent to give adequate advice how to transition to
new shoes. The same happens when someone chooses to run barefoot. So, the aim of
the present experiment was to find out whether giving or not giving an
explanation of the correct technique of foot placement in barefoot running and
running in a minimalistic shoe influences the frequency of rear-foot strikes in
natural, rear foot strikers when running barefoot or in minimalistic shoes.
Thirty-nine subjects (age =34.9 +/- 6.9 years, height = 174 +/- 9 cm, mass = 73.1
+/- 13.8 kg), randomly divided into four groups participated in this experiment.
Subjects in groups 1 and 3 did not receive an explanation, while groups 2 and 4
did. Besides the difference in explanation, there was also a difference in the
shoes worn during the intervention. Subjects in the groups 1 and 2 ran barefoot,
while subjects in groups 3 and 4 ran in minimalistic shoes. The initial state of
the foot strike patterns was measured in classic running shoes. During the
intervention subjects ran according to the group they were in. 80% of the
subjects in groups 1 and 3 took the most steps in a rear-foot strike pattern
(Median =100) while only 21% of the subjects in groups 2 and 4 took the most
steps in a rear-foot strike pattern (Median = 15.7), U = 64, z = 3.619, p (0.00)
< 0.05, r = -0.58. The results show that an explanation and dem-onstration of the
correct technique of foot placement in barefoot running and running in a
minimalistic shoe is important when someone decides to switch from classic
running shoes to minimalistic shoes or to go barefoot.
PMID- 26434022
TI - The Relationship between Selected Motor Ability Determinants and Anthropometric
Characteristics in Adolescent Athletes from Various Sport.
AB - The main purpose of this study was to examine the relationship between speed,
lower extremities explosive power, simple, and complex responses in adolescent
athletes from various disciplines. Thirty nine athletes of 16.5 years old, N = 13
sprinters and jumpers, N = 13 soccer players, and N = 13 judokas participated in
the experiment. Pearson correlations, a one-way ANOVA and an independent t-test
for establishing differences between those three groups of athletes was applied.
Additionally the Ward method of hierarchical cluster analysis also was applied.
The strong correlation occurred between complex responses and speed; 20 m from
standing and 20 m flying start (r = 0.62 and r = 0.65 respectively). In other
cases, no strong association was found. The substantial differences between
groups occurred in the 20 m run from flying start (t = 5.92) and standing triple
jump (t = 4.16). The study indicates that adolescent athletes may need to be
assessed differently to a certain extent, including sport specialization.
PMID- 26434024
TI - Effects of Neuromuscular Electrical Stimulation and Resistance Training on Knee
Extensor/Flexor Muscles.
AB - Neuromuscular electrical stimulation (NMES) has recently drawn a lot of attention
as means for strengthening of voluntary muscle contraction both in sport and
rehabilitation. NMES training increases maximal voluntary contraction (MVC) force
output through neural adaptations. On the other hand, positive effects of
resistance training (RT) on muscle strength are well known. The aim of this study
was to investigate effects of a 5-week program of NMES compared to RT program of
same duration. Sample of 15 students' of faculty of sport and physical education
(age 22 +/- 2) were randomized in two groups: NMES (N = 7) and RT (N = 8). NMES
group performed NMES superimposed over voluntary muscle contraction, RT group
performed resistance training with submaximal loads. Subjects were evaluated for
knee isokinetic dynamometry on both sides (60 degrees and 180 degrees s). After
intervention no significant difference between groups were observed in isokinetic
dynamometry (p = 0.177). However, applying pair sample t test within each group
revealed that peak torque increased in NMES-group (p = 0.002 for right knee
extensors muscles, p = 0.003 for left, respectively, at 60 degrees and p = 0.004
for left knee extensors muscles, at angular velocity 180 degrees ). In RT group
(p = 0.033 for right knee extensors muscles, p = 0.029 for right knee flexor
muscles, at angular velocity 60 degrees ). Our results indicate that NMES has
equal potential if not in some way better than classical RT having in mind that
overload on locomotor apparatus during NMES is minimal and force of muscle
contraction is equal on both sides, for enhancement of knee muscles concentric
peak torque.
PMID- 26434025
TI - Kinematic, Dynamic and EMG Analysis of Drop Jumps in Female Elite Triple Jump
Athletes.
AB - The purpose of the study was a biodynamic analysis of the kinematic, dynamic and
EMG parameters of two types of drop jumps (heights of 25 cm and 45 cm). The
sample of measured subjects included four female elite triple jump athletes, with
their best results varying from 13.33 to 15.06 meters. The kinematic and dynamic
parameters were calculated with the use of a bipedal tensiometric force plate,
which was synchronized with nine CCD cameras. A 16-channel electromyography (BTS
Pocket, Myolab) was used to analyze the EMG activation of the following muscles:
m. erector spinae, m. gluteus, m. rectus femoris, m. vastus medialis, m. vastus
lateralis, m. biceps femoris, m. soleus and m. gastrocnemius medialis. In the
drop jump from a 25 cm height, the measured subjects achieved the following
results: height of jump 43.37 +/- 5.39 cm and ground reaction force 2770 +/- 411
N. In comparison, results for the drop jump from a 45 cm height were: height of
jump 45.22 +/- 4.65 cm and ground reaction force 2947 +/- 366 N. Vertical
velocity of the take-off in the 25 cm drop jump was 2.77 +/- 0.19 ms(-1) and in
the 45 cm drop jump it was 2.86 +/- 0.15 ms(-1). Observation of the EMG
activation revealed the proximal to distal principle of muscle activation at work
in both types of drop jumps. In the first phase of the concentric phase the most
active muscles were m. gluteus maximus and m. rectus femoris. The greatest
activity of m. gastrocnemius medialis and m. soleus was noticed in the last third
of the take-off action. Significantly high EMG activation of m. vastus medialis
and m. vastus lateralis was already shown in the flight phase prior to the feet
making contact with the ground.
PMID- 26434026
TI - Activation Pattern of Lower Leg Muscles in Running on Asphalt, Gravel and Grass.
AB - Running is performed on different natural surfaces (outdoor) and artificial
surfaces (indoor). Different surface characteristics cause modification of the
lower leg muscle activation pattern to adopt ankle stiffness to these
characteristics. So the purpose of our investigation was to study changes of
lower leg muscles activation pattern in running on different natural running
surfaces. Six male and two female runners participated. The participants ran at a
freely chosen velocity in trials on asphalt while in trials on gravel, and grass
surfaces they were attempting to reach similar velocities as in the trials on
asphalt. Muscle activation of the peroneus brevis, tibialis anterior, soleus, and
gastrocnemius medialis of the right leg was recorded. Running on asphalt
increased average EMG amplitude of the m. tibialis anterior in the pre-activation
phase and the m. gastrocnemius medialis in the entire contact phase compared to
running on grass from 0.222 +/- 0.113 V to 0.276 +/- 0.136 V and from 0.214 +/-
0.084 V to 0.238 +/- 0.088 V, respectively. The average EMG of m. peroneus brevis
in pre-activation phase increased from 0.156 +/- 0.026 V to 0.184 +/- 0.455 V in
running on grass in comparison to running on gravel. Running on different
surfaces is connected with different activation patterns of lower leg muscles.
Running on asphalt requires stiff ankle joints, running on gravel requires
greater stability in ankle joints, while running on grass is the least demanding
on lower leg muscles.
PMID- 26434028
TI - Environmental Success Factors or the Justification for the Prohibition of High
Tech Swimsuits in Swimming.
AB - The scope of the study was to elaborate and represent different aspects of high
tech suits which influence the swimming results and to justify the change of
swimming rules in 2009. Impact of environmental factors on the result should not
be greater than the athlete's impact. Impact of high-tech suits greatly
contributes to the development of technology, new materials and modern design of
sports equipment. The paper describes the genesis of the high-tech swimsuits and
provides an analysis of causes and consequences of its prohibition. The arguments
against the suits have an effect on prohibition of different sports requisites
and equipment in all sports. This prohibition directly affects the modern
swimmers who will have difficulties in breaking the world records swimming in
high-tech suits.
PMID- 26434027
TI - Motor Skills in Hearing Impaired Children with or without Cochlear Implant--A
Systematic Review.
AB - Hearing impairment is a major limitation in communication, and it can obstruct
psychological development, development of social skills and motor development.
Hearing impairment is the third most common contemporary chronic health
condition, and it has become a public health problem. The effectiveness of
problem solving in everyday life and in emergency situations depends greatly on
the amount and quality of the motor programs. Therefore, it is evident that the
normal motor development in persons with hearing impairment is essential for
everyday life. The aim of this research is to analyze the available information
pertaining to motor skills of hearing impaired children both with and without a
cochlear implant (CI) and to analyze possibilities of influencing their motor
skills. The relevant studies on motor skills of hearing impaired children both
with and without CI were obtained by an extensive computer search of various
databases using special keywords and extraction with respect to certain criteria,
resulting in 22 studies. The overall results of this systematic review indicate
that the children with hearing impairment exhibit suboptimal levels of motor
skills especially balance. Very few studies compared children with hearing
impairment with CI units and without CI units and the results of those studies
are quite contradictory. Numerous studies have confirmed that the regular and
appropriate physical exercise can improve motor skills of children with hearing
impairment, especially balance. The fact that the development of motor skills is
crucial for the child's interaction with the outside world, action, perception
and acquisition of academic skills and other skills necessary for life shows the
importance of motor skills development for children with hearing impairment.
PMID- 26434029
TI - Physical Activity as a Function of Women's Health.
AB - Physical activity means any form of body movement that is associated with certain
metabolic demands. At the same time, physical activity is one of the most
important steps in the maintenance, protection and improvement of health. There
is strong evidence to suggest that higher levels of physical activity are
associated with numerous preventive effects and therapeutic effects in the
treatment of many diseases. Although they account for a larger portion of the
population, physical inactivity is more often registered in women, which can be
attributed to a variety of reasons--ranging from anatomical and physiological to
the socio-psychological. The present paper discusses some of the most important
benefits associated with physical activity in women, to encourage their greater
participation in various forms of physical activity.
PMID- 26434030
TI - Evidence-Based Practice: Share the Spirit of Inquiry.
PMID- 26434031
TI - It's Time to Recognize APRN Practice Nationally.
PMID- 26434032
TI - The Gluten-Free Frenzy: Fad or Fitting?
AB - Although the gluten-free diet has been recognized as therapeutic for individuals
suffering from celiac disease, it has been promoted recently for other
indications, such as autism, chronic fatigue syn- drome, and irritable bowel
syndrome, or simply as a healthy dietary choice for anyone. The basics of the
gluten-free diet are explored, with evidence-based indications and nursing
implications when patients choose gluten-free.
PMID- 26434033
TI - Sensitivity and Specificity of a Nurse Dysphagia Screen in Stroke Patients.
AB - PURPOSE: To determine how well an institutionally developed nurse dysphagia
screening tool correctly identified the presence (sensitivity) or absence
(specificity) of dysphagia in patients following acute stroke. METHODS: A method
comparison design was used to compare results of the Nurse Dysphagia Screen to
the dysphagia evaluation by a speech and language pathologist (SLP). Each newly
diagnosed participant served as his or her control, with both dysphagia
evaluations (nurse, SLP) occurring within 2 hours of each other. Sensitivity and
specificity of the Nurse Dysphagia Screen was calculated using standard formulas.
RESULTS: For 49 patients evaluated following stroke, average age was 71.7 (SD +/-
13.5). Twenty-five subjects were female and 24 were male. The majority of the
participants had strokes identified as ischemic in origin (n=35). The SLP found
18 (37%) participants had a positive dysphagia assessment. The Nurse Dysphagia
Screen was positive in 16 of 18 participants screened positive by SLP, resulting
in some type of dietary restriction. The Nurse Dysphagia Screen was negative in
28 of the 31 patients screened as negative by SLP. Sensitivity and specificity of
the Nurse Dysphagia Screen were 89% and 90%, respectively. CONCLUSIONS: An easy
to-use, institutionally developed nurse dysphagia screening tool successfully
identified patients with swallowing difficulties after stroke later diagnosed by
SLP.
PMID- 26434034
TI - 'I'm Not Calling Him!': Disruptive Physician Behavior in the Acute Care Setting.
AB - Results of a qualitative study of the experience of 15 acute care nurses with
disruptive physician behavior and its impact on communication are reported.
Findings will help educators and leaders prepare nurses by coaching and educating
them on the importance of communication and patient advocacy.
PMID- 26434035
TI - Is Nursing Care Missed? A Comparative Study of Three North Carolina Hospitals.
AB - Results of a survey measuring frequency, types, and reasons for missed care at
three acute care hospitals in North Carolina are described. Results also are
compared to those of a previous, similar study in the midwestern United States.
PMID- 26434036
TI - Use of a Soft Silicone Foam Dressing to Change the Trajectory of Destruction
Associated with Suspected Deep Tissue Pressure Ulcers.
AB - PURPOSE: To explore the evolution of suspected deep tissue injury (sDTI) pressure
ulcers and identify the role of early identification and intervention in
hindering tissue destruction. In contrast to previously published evidence, the
foundational research identified a significant trend of sDTI recovery which
warranted further analysis. SUBJECTS AND SETTINGS: A single-site, 24-month
retrospective, IRB-approved study evaluated 77 adult (age 18 or older)
hospitalized subjects with 128 wound care nurse-identified sDTIs over the course
of 1 day to 14 weeks for 377 encounters. METHODS: Data from a 24-month period
(2010-2012) were analyzed during the primary study. In addition to demographics,
the evolution process including site, initial presentation, measurements, tissue
consistency, and treatment, were assessed. In response to findings of significant
sDTI recovery, a secondary in-depth analysis focused on commonalities and
variables for clarity of their contribution to the isolated improved patient
outcomes. RESULTS: In addition to clearer delineation of demographics, co-morbid
conditions, and evolutionary patterns, the researcher identified patient outcomes
in stark contrast to those previously published in the literature. A significant
outcome of resolution of sDTI pressure ulcers was observed. Upon further review,
the role of absorbent soft silicone, multi-layer, self-adherent bordered foam
(Mepilex) in these outcomes was elucidated clearly.
PMID- 26434037
TI - Postoperative Complications and Emergency Care for Patients Following Bariatric
Surgery.
AB - Evidence-based practice for multiple types of bariatric surgeries is addressed,
along with complications, signs and symptoms of a postoperative emergency with
the correct course of action, and general postoperative care.
PMID- 26434038
TI - Exploration of Nurse Practices and Attitudes Related to Postoperative Vital
Signs.
AB - Analysis of surgical nurses' attitudes toward postoperative vital sign (VS)
assessment found tradition and ritual rather than research continue to drive
postoperative VS assessment practices. Recommendations for practice, education,
and research are made based on these findings.
PMID- 26434039
TI - Postoperative Delirium Prevention in the Older Adult: An Evidence-Based Process
Improvement Project.
AB - Postoperative delirium is a major complication in hospitalized older adults.
Implementation of a screening tool and evidence-based delirium-prevention
protocol on a surgical unit increased nurses' knowledge regarding delirium,
increased identification of delirium, and produced medical treatment alterations
leading to positive patient outcomes.
PMID- 26434041
TI - Nursing Implications of Research.
PMID- 26434040
TI - Coping with Death and Dying in Afghanistan: A Reflection.
PMID- 26434042
TI - The New 'Code of Ethics for Nurses With Interpretive Statements' (2015):
Practical Clinical Application, Part I.
PMID- 26434043
TI - Inflammatory Bowel Disease: Caring for a Patient with Crohn's Disease.
AB - The Medical-Surgical Nursing Certification Board (MSNCB) encourages certification
for all registered nurses who provide care in a medical-surgical setting. Initial
certification is achieved through successful testing by written examination. The
certification examination is based on Benner's Nursing Model. Questions on the
examination fall within the seven domains of nursing practice: Helping Role,
Teaching-Coaching Function, Diagnostic and Patient Monitoring, Effective
Management of Rapidly Changing Situations, Administering and Monitoring
Therapeutic Interventions and Regimens, Monitoring and Ensuring the Quality of
Health Care Practices, and Organizational and Work Role Competencies. The
examination is designed to assess comprehensive knowledge of medical-surgical
nursing. The medical-surgical practitioner must understand diseases, diagnoses,
and treatment modalities to function as a caregiver and educator. The topic of
this article is a part of the comprehensive examination given by MSNCB. The
following scenario and questions offer an example that potential certificants may
use to test their knowledge. For more information about MSNCB, visit
www.amsn.org/certification.
PMID- 26434044
TI - Nursing Care Considerations: The Epidural Catheter.
PMID- 26434045
TI - The Voice--of Email.
PMID- 26434046
TI - Promoting Success in Self-Injection: Listening to Patients.
PMID- 26434048
TI - HealthyNurse Healthy Work Environment = Your Health, Safety, and Wellness.
PMID- 26434047
TI - The Influence of Health Care Literacy on the Use of PHRs among Older Adults.
PMID- 26434049
TI - Ohio's Safe Nurse Staffing Law.
PMID- 26434050
TI - Social Media in Healthcare: Safeguarding Healthcare Staff.
PMID- 26434052
TI - HSDM Awarded Major NIH Grant in Pain-Management Education.
PMID- 26434053
TI - A New Way to Learn Clinical Skills.
PMID- 26434054
TI - HSDM at the National Oral Health Conference.
PMID- 26434055
TI - FROM THE DEAN.
PMID- 26434056
TI - Class of '44 Members Studied Together, Went to War Together.
PMID- 26434057
TI - Mortimer Lorber, DMD '50, MD '52.
PMID- 26434058
TI - History of Oral and Maxillofacial Surgery.
PMID- 26434059
TI - Making Stem Cells from Mature Cells.
PMID- 26434060
TI - HSDM Research Targets Osteoarthritis.
PMID- 26434061
TI - The Electronic Health Record as Research Tool.
PMID- 26434062
TI - Enhancing Advanced Graduate Education.
PMID- 26434063
TI - To Give and Receive.
PMID- 26434064
TI - Operation Mouthguard.
PMID- 26434066
TI - From the Dean.
PMID- 26434065
TI - Biotechnology in Developing-Country Health Care.
PMID- 26434067
TI - The Goodman Family Embodies Philanthropy.
PMID- 26434068
TI - John and Peggy Rusnock Give Back.
PMID- 26434069
TI - Aleksander Iofin, DMD '01: Gratitude for a "Second Life".
PMID- 26434070
TI - Lorne Golub, PD '68, Brings Dental Research into Medicine.
PMID- 26434071
TI - HSDM Students Protect Young Athletes' Mouths.
PMID- 26434072
TI - Delivering Oral Health Care in Colombia.
PMID- 26434073
TI - Providing Care in Ecuador.
PMID- 26434074
TI - Research Toward a "Fat-Busting Pill".
PMID- 26434075
TI - President's Message.
PMID- 26434076
TI - Rapidly Progressive Seeding of a Community Acquired Pathogen in an Immune
competent Host--End Organ Damage from Head to Bone.
AB - This report describes a 64-years-old male patient that presented to our hospital
with a chief complaint of acute worsening of his usual chronic lower back pain,
progressive weakness in lower extremities and subjective fevers at home. Spine CT
failed to demonstrate any infectious foci but showed partially visualized lung
cavitary lesion and renal pole abnormalities. Blood cultures grew methicillin
sensitive Staphylococcus Aureus (MSSA). Transthoracic echocardiogram (TTE) showed
no signs of infective endocarditis (IE). Later, the patient experienced an acute
deterioration on clinical status and examination showed development of a new
murmur. He also developed new hemiparesis with up-going babinski reflex. A head
MRI showed multiple infarcts. MRI spine displayed osteomyelitis at T12-L1.
Cerebro-spinal fluid was positive for meningitis. A transesophageal
echocardiogram (TEE) was performed demonstrating new severe mitral and mild
tricuspid regurgitations with a definitive 1.5 cm mobile vegetation on posterior
mitral leaflet. We present is a very interesting case of a rapidly progressive
MSSA infection. MSSA meningitis is a rare disease; there are only few reported
cases in the literature to date. We describe a case of MSSA bacteremia, of
questionable source, that resulted in MSSA endocarditis affecting right and left
heart in a patient who did not have a history of intravenous drug use (IVDU) or
immunosuppression. The case was complicated by septic emboli to systemic
circulation involving the kidneys, vertebral spine (osteomyelitis), lungs and
brain with consequent meningitis and stroke. Even when MSSA infections are well
known, to our knowledge there are no previous case reports describing such an
acute-simultaneous-manifestation of multi-end-organ failure, including meningitis
and stroke. These latter are rarely reported, even individually.
PMID- 26434077
TI - Knee avascular necrosis in HIV patient.
PMID- 26434078
TI - Endoscopic- Assisted Trephination approach for repair of Frontal Sinus posterior
wall fracture in a Child.
AB - A 9 year-old male sustained multiple maxillofacial fractures after falling from a
two-store building. Frontal sinuses suffered a bilateral non-displaced linear
fractures extending into the anterior and posterior walls. Magnetic resonance
imaging (MRI) at this time showed a small encephalocele extending into the right
frontal sinus. Operative repair was performed using an Endoscopic-Assisted
Trephination approach.
PMID- 26434079
TI - Endoscopic Resection of a Posterior Nasal Septum Pleomorphic Adenoma.
AB - A 60 year-old female presented to our clinic with a two-year history of
progressive nasal obstruction and one isolated episode of epistaxis that did not
respond to medical treatment. Endoscopic evaluation revealed roundish, dumbbell
shape, smooth-surfaced, submucosal mass with prominent vessels of approximately 2
cm in the posterior nasal septum,. A paranasal CT scan revealed a well
circumscribed oval shape mass (1.7 cm x 1.6 x 1.5 cm) arising from the posterior
border of the bony nasal septum. The tumor was removed en-bloc with 1-centimeter
free margins confirmed by intra-operative frozen sections through a completely
endoscopic approach. Pathology results confirmed the diagnosis of a pleomorphic
adenoma.
PMID- 26434080
TI - Isolated Xanthoma Of The Sphenoid Sinus: A Rare Presentation.
AB - OBJECTIVE: To present the first case in the English literature of a sphenoid
xanthoma. METHODS: Case Report DISCUSSION: A 36 year-old Hispanic female with
past medical history of Hashimoto's hypothyroidism and family history of
hyperlipidemia that presented with a 1-year history of sporadic left sided
epistaxis. A paranasal sinus Computed Tomography (CT) was performed revealing a
soft tissue lesion infiltrating the left sphenoid sinus. Patient underwent
endoscopic sinus sphenoidotomy with intraoperative findings of a yellow-tan,
friable soft tissue mass filling the left sphenoid sinus. Biopsies were taken
which exhibited histologically findings consistent with a xanthoma. CONCLUSION:
In a patient with hyperlipidemia isolated lesions on paransasal sinuses can be
related to xanthoma formation.
PMID- 26434082
TI - Case Report: Prothesis-patient mismatch after aortic valve replacement.
AB - Valve replacement is the standard surgical treatment of diseased valves that
cannot be repaired. The main goal of replacement is to exchange the diseased
valve with one that has the engineering and hemodynamics as close as possible to
the disease free native valve. However due to mechanical and fluid dynamic
constraints all prosthetic heart valves (PHVs) are smaller than normal and thus
are inherently stenotic. This represents a challenge when it comes time to
replace a valve. The correct valve with the correct and matching profile has to
be selected before the procedure to avoid possible complications. It is well
recognized that patients are also prone to patient-prosthesis mismatch at long
term which could have consequences in the clinical outcomes (1). The evaluation
of patient-prosthesis mismatch (PPM) has not been sufficiently emphasized in
common practice. Failure to recognize this fact may lead to significant
hemodynamic impairment and worsening of the clinical status over the time. Making
efforts to identifying patients at risk may decrease the prevalence of PPM, the
economic impact to our health system, the morbidity and mortality involved in
these cases as well as creates efforts to standardized pre-operative protocols to
minimized risk of PPM. We present a case of a 78 years old male patient who
underwent aortic valve replacement due severe aortic stenosis, afterwards his
clinical course got complicated with several admissions for shortness of breath
and decompensated congestive heart failure (CHF).
PMID- 26434081
TI - Manati Medical Center Sepsis Management Epidemiological Study.
AB - Sepsis is the combination of infection and physiological changes known as the
systemic inflammatory response syndrome. There have been improvements in
mortality rates and outcomes of septic patients based on "Surviving Sepsis
Campaign" guidelines. Current management of sepsis at our Institution follows no
specific mandatory protocols. This study aimed to verify the incidence and
outcome of sepsis in Manati Medical Center, Puerto Rico. An observational
retrospective study was conducted. All the Emergency Department admissions from
May 1/ to October 31/ 2013 were screened for sepsis per ICD-9 code. For all
included patients, demographic and clinical data at ED admission were collected.
During this period 8931 patients were admitted and 148 met criteria for sepsis
and related conditions. The overall mortality rate was 43.91%. Mortality
increased with age, from 10.52% among <= 44 years old to 68.75% in those >= 85
years old. The main infection sources were respiratory (32.66%) and urinary tract
(24.62%). Mean age among non-survivors was 10.8 years higher than the survivor
group (95% Cl 5.2-1 6.5, p < 0.05). Multivariate analysis showed an increased
fatality rate associated to severity of sepsis (HR 1.33; 95% Cl; 1.03-1.72, p =
0.02) and the APACHE2 score (HR 1.05; 95% Cl, 1.01-1.09 p = 0.03). Our data
suggests that sepsis is an important problem to consider. We strongly encourage
an institutional standardized protocol to diminish the mortality impact. Our
results will allow adequate preventive strategies to improve early diagnosis,
mortality rates and outcomes of septic patients.
PMID- 26434083
TI - Surviving Sepsis Puerto Rico: A Call For Action.
AB - There are 1.7 million sepsis-related hospitalizations each year making it the
sixth most common cause for hospitalization in the United States. Not only are
this hospitalizations common, they are expensive to our medical system with $15.3
billion spent yearly (3) and hospitalizations lasting 75% longer than for other
conditions. In 2001, Rivers et al published in the NEJM the results of his study
"Early Goal Directed Therapy (EGDT) in The Treatment of Severe Sepsis and Septic
Shock". EGDT demonstrated a 16.5% decrease in mortality in septic patients (4).
In 2002 the Surviving Sepsis Campaign began as a collaboration between the
Society of Critical Care Medicine and European Society of Intensive Care Medicine
with goals of reducing worldwide sepsis related mortality by 25% in the next 5
years. Despite the proven benefit of early identification and management,
knowledge regarding the topic in Puerto Rico remains scarce. In a study performed
in PR by Fernandez et al. in 2006, only an alarming 31.4% of doctors from
different specialties correctly identified SIRS criteria. Our goal is to educate
physicians about the importance of early identification and treatment of the
septic patient. A campaign to increase awareness and improve care is essential
and we propose treatment protocols for our Puerto Rican hospitals to help reduce
morbidity, mortality, length of stay and costs.
PMID- 26434084
TI - Dengue Fever: A Rare Cause Of Immune Thrombocytopenia.
AB - Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low
platelet count and skin-mucosal bleeding. In adults it is usually idiopathic and
may have a chronic onset, while in children it is usually acute following a viral
illness. Dengue has been rarely reported as a cause of ITP. We report a case of a
young adult woman that presented with acute ITP following a dengue virus
infection.
PMID- 26434085
TI - Metabolic Correction as a tool to improve diabetes type 2 management.
AB - Diabetes Mellitus type 2 (DM2) is a metabolic disease that develops by a decrease
in sensitivity of insulin receptors as an effect of the disruption certain
metabolic functions in the processing of glucose. DM2 patients have, uncontrolled
glucose levels, and commonly have problems with obesity and cardiovascular
disease. Patients are treated with standard diet, insulin, diabetic oral agents
and antihypertensive drugs, but this approach does not completely stops tissue
deterioration since it does not address the metabolic root of the disease.
Metabolic correction is proposed as a suitable adjunct treatment to improve
clinical outcomes. Metabolic correction is based on diet modification, proper
hydration and scientific supplementation directed to improve cellular
biochemistry and metabolic efficiency. In addition, other possible benefits may
include reduction in medication use, disease complications and medical costs. To
test the results of a metabolic correction program, 25 patients with DM2
participated in an education program about adequate food consumption that
promoted control of blood glucose levels. Anthropometric measurements and blood
tests were performed during a 13 week program based on a low carbohydrate diet,
proper hydration and magnesium supplementation. The metabolic correction program
implemented by a proprietary educational system resulted in significant
reductions in glucose, triglycerides, cholesterol, weight and waist
circumference. Improvements in these values could represent an important
reduction of coronary heart disease risk factors as well as other chronic
degenerative diseases. In addition there was medication dosage reduction in one
or more medications in 21 of the 25 participating patients, which suggest that
the program has the potential to improve health outcomes and reduce health care
costs.
PMID- 26434086
TI - [Metabolic correction: a biochemical option against diseases].
AB - Human development and its physiology depends on a number of complex biochemical
body processes, many of which are interactive and codependent. The speed and the
degree in which many physiological reactions are completed depend on enzyme
activity, which in turn depends on the bioavailability of co-factors and
micronutrients such as vitamins and minerals. To achieve a healthy physiological
state, organism need that biochemical reactions occur in a controlled and
specific way at a particular speed and level or grade fully completed. To achieve
this, is required an optimal metabolic balance. Factors such as, a particular
genetic composition, inadequate dietary consumption patterns, traumas, diseases,
toxins and environmental stress all of these factors rising demands for nutrients
in order to obtain optimal metabolic balance. Metabolic correction is a
biochemical and physiological concept that explains how improvements in cellular
biochemistry of an organism can help the body achieve metabolic and physiological
optimization. We summarize the contribution of several pioneers in understanding
the role of micronutrients in health management. The concept of metabolic
correction is becoming a significant term due to the presence of genetic variants
that affect the speed of reactions of enzymes, causing metabolic alterations that
enhance or promote the state/development of multiple diseases. Decline in the
nutritional value of the food we eat, the increase in demand for certain
nutrients caused by normal development, diseases and medications induce, usually,
nutrients consumption. These nutritional deficiencies and insufficiencies are
causing massive economic costs due to increased morbidity and mortality in our
society. In summary, metabolic correction improves the enzymatic function, which
favors the physiological normal functions, thus, contributing to improving health
and the welfare of the human being. The purpose of this paper is to describe and
introduce the concept of optimal metabolic correction as a functional cost
effective mechanism against disease, in addition, to contribute to diseases
prevention and regeneration of the body and health.
PMID- 26434087
TI - Brugada Syndrome in Puerto Rico: a Case Series.
AB - Brugada syndrome (BrS) is characterized by ST-segment changes in the right
precordial ECG leads and a high incidence of sudden death in patients with
structurally normal hearts. Life-threatening ventricular arrhythmias are the
hallmark of Brugada syndrome. The incidence and prevalence of BrS in Puerto Rico,
to our knowledge, has never been studied and there is only one case report of BrS
in Puerto Rico in the literature [1]. We present 3 cases of BrS in Puerto Rican
patients who presented to our institution with syncope and review the literature.
PMID- 26434088
TI - 23 y/o female with dysphagia--Evaluation, intervention and resolution of symptoms
in the Psychiatry consultation setting.
AB - Dysphagia is a symptom shared by many medical and psychiatric conditions. A
thorough Psychiatric evaluation could rule in a functional or psychological
etiology. If a Psychological etiology is identified, a psychodynamic formulation
could help the consultation psychiatrist clarify the origin of the symptom and
provide a better explanation to the patient and medical team, resulting in
improved care by prevention of unnecessary medical interventions, improvement of
symptoms and individualization of the treatment.
PMID- 26434089
TI - Functional Brain Imaging in Cornelia de Lange Syndrome: Case Report and
Literature review.
AB - Functional brain imaging with brain single photon emission computer tomography
(Brain SPECT) has been used for many years in the evaluation of multiple neuro
degenerative and neuro-developmental disorders. Brain SPECT is a nuclear medicine
tomographic study performed with a lipophilic radiopharmaceutical labeled with
99mTc-pertechnetate. It is a cerebral perfusion agent that depicts the global and
regional perfusion patterns in the cortical gray matter and subcortical
structures. Cornelia de Lange syndrome (CdLS) is a rare neuro-developmental and
genetic condition, associated to several malformations. There are a limited
number of cases reported in the medical literature and few of them report neuro
radiological and/or neuro-pathologic abnormalities. We report a case of a 15 year
old patient, clinically diagnosed at birth with CdLS, who presents limited
anatomical findings on Computed Tomography and Magnetic Resonance Imaging. To the
best of our knowledge, this is the first report of the Brain SPECT findings in
this syndrome.
PMID- 26434090
TI - Does Injection Site Matter? A Randomized Controlled Trial to Evaluate Different
Entry Site Efficacy of Knee Intra-articular Injections.
AB - BACKGROUND: Complaints of knee pain secondary to early osteoarthritis may account
for up to 30% of visits to primary care physicians. Due to the proposed
inflammatory changes in early osteoarthritis, intra-articular injections of
corticosteroids (IACS) have been considered as an option for disease progression
modification, pain control, and improvement of function. However, some studies
have suggested poor accuracy rates of IA injections depending on the entry site
chosen. It is therefore the aim of this study to evaluate the efficacy of IA knee
corticosteroid injection in reducing pain and improving function in patients with
early osteoarthritis and whether the low accuracy rates reported with the
Anterolateral joint line injection site translate to worse functional and pain
outcome measures as compared to Suprapatellar lateral injections. MATERIALS AND
METHODS: The study was carried out as an open-label, randomized controlled trial
with 60 sequential patients recruited. Simple randomization separated groups into
anterolateral joint line or suprapatellar lateral injection sites. Improvements
were measured with WOMAC and VAS scores after injection of Lidocaine and steroid
solution. RESULTS: Patients receiving IACS injections had a measurable
improvement in self-reported outcomes as evidenced by standard deviation change
in WOMAC and VAS scores. The majority of patients had a clinically significant
improvement in VAS scores as compared to their initial measures with a notable
amount of patients improving significantly as well on their WOMAC scores,
irrespective of the injection site chosen. CONCLUSIONS: We have therefore
continued the use of palpation-guided intra-articular knee injections in an
effort to reduce costs as compared to other injection modalities with positive
results in our osteoarthritis patients.
PMID- 26434092
TI - Acquired Von Willebrand Syndrome In Aortic Stenosis: Case Report And Review.
AB - We present a case of a 61 year old man who presented with a 3 week history of
easy bruising and ecchymoses in both thighs and right arm without significant
trauma. Physical exam was remarkable for oozing gums, diminished second heart
sound, a systolic ejection murmur at the aortic position with radiation to
carotids, and delayed pulses. Laboratories were remarkable for iron deficiency
anemia. Echocardiogram was consistent with severe aortic stenosis. Colonoscopy
revealed several arteriovenous malformations throughout the colon. There is an
association between severe aortic stenosis and gastrointestinal bleeding. The
pathogenesis of Heyde's Syndrome involves iron deficiency anemia due to acquired
von Willebrand factor (vWF) deficiency and ultimately gastrointestinal
angiodysplasia. Correct diagnosis and management warrants a multidisciplinary
approach.
PMID- 26434091
TI - Use of Screening Tests for Colorectal Cancer Among Gynecologists in Puerto Rico.
AB - OBJECTIVE: To determine the use of screening tests for colorectal cancer (CRC)
among Gynecologists in Puerto Rico. This study evaluates the screening practices
used by Gynecologists in PR to diagnose CRC and adherence to screening
guidelines. METHODS: A self-administered anonymous questionnaire was mailed to
440 practicing gynecologists through the College of Physicians and Surgeons of
PR. The questionnaire included general and specific questions. RESULTS: Response
rate was 23.2% (102/440). Of this group of gynecologists, 77.5% referred
screening patients, while 22.5% did not. The majority (28.4%) use Fecal Occult
Blood Test (FOBT) as a first screening test, while 27.5% use Colonoscopy.
Screening is started by 49% at age 50. Only 7% stop screening at 75 years and 31%
never stop screening. CRC Screening performed by participants were: 35% screen
annually, 6% screen 2-3 years, 10% screen every 5 years, 6% screen every 10 years
and 6% screen 5-10 years. Data for CRC Screening reveals 7% gynecologists comply
with all the guidelines; 49% comply with the recommendations regarding the start
screening age and 7% stop screening as per guidelines. CONCLUSION: The
recommendations are not followed by most of the gynecologists in PR that
participated in the study, Further research should be directed towards the
reasons for not complying and how to educatethemedical population to achieve
adequate screening in the PR female population.
PMID- 26434093
TI - Do We Need Hormonal Screening In Patients With Subcentimeter Pituitary
Microadenomas?
AB - A 54-year-old woman came to our endocrinology clinics presenting with upper and
lower extremity paresthesia, salt cravings, episodes of hypotension, fatigue and
a long term history of depression. Physical exam was unremarkable. Cervical and
brain MRI ordered by her neurologist three years ago revealed sella and pituitary
normal in size, stable very small 3 mm pituitary incidentaloma and mild disc
bulging. Basal pituitary hormonal screening showed low cortisol and ACTH levels.
Insulin Tolerance Test and Glucagon Stimulation Test confirmed secondary ACTH
deficiency with concomitant GH deficiency. In spite of medical counseling the
patient refused glucocorticoid replacement. Due to the non-specific symptoms of
this condition it remains a challenge to be diagnosed by clinicians. In
conclusion: Our case shows that hormonal deficiencies may occur in small tumors
less than 6 mm.
PMID- 26434094
TI - Lack of training and Comfort level with Provision of Palliative Care in Puerto
Rican Emergency Departments.
AB - OBJECTIVE: Although many institutions in the United States have incorporated
palliative care practices in their emergency departments, very little has
occurred in Puerto Rico. Information regarding palliative care training of
emergency medicine physicians in Puerto Rico is unclear and most physicians have
poor or no access to palliative care services for their patients. This study
explores the perceptions and barriers encountered by practicing emergency
physicians in providing palliative care in Puerto Rican Emergency Departments.
METHODS: A survey was administered to physicians attending the American College
of Emergency Physicians Puerto Rico Chapter annual Convention Attending
physicians and residents from the University of Puerto Rico School of Medicine
validated the survey tool via a "content validity" approach. Participants were
asked to respond to Likert scaled statements with options that ranged from
"Strongly Agree" to "Strongly Disagree". The statements addressed physician
comfort level with provision of palliative care and discussion of end of life
issues, as well as barriers encountered by providers such as time constraints,
fear of lawsuits, and lack of access to specialists among others. RESULTS: Of the
85 physicians at the convention 59 provided surveys available for review for a
response rate of 70%. Of those surveyed, 35% reported feeling some level of
discomfort at providing palliative care in the ED and 39.6% agreed or strongly
agreed that their lack of training in palliative care affects their ability to
provide this service. In addition, 81% lack access to palliative care
specialists/teams in the emergency department. However, 82.8% agreed or strongly
agreed that palliative care is an important competence for emergency physicians.
CONCLUSIONS: Despite recognizing palliative care as an important competence,
emergency physicians in Puerto Rico reported insufficiencies in training,
decreased level of comfort, and lack of access to specialists in palliative care.
Efforts to enhance physician training and provide palliative care resources must
be pursued in order to improve the quality of care given to patients visiting
Puerto Rican Emergency departments.
PMID- 26434095
TI - Are Young Adults with ADHD Undertreated?
PMID- 26434096
TI - [Glutamic acid as a universal extracellular signal].
AB - The prevailing view is that both glutamic (Glu) and gamma-aminobutyric (GABA)
acids play a role as an amino acid neurotransmitter released from neurons.
However, little attention has been paid to the possible expression and
functionality of signaling machineries required for amino acidergic
neurotransmission in cells other than central neurons. In line with our first
demonstration of the presence of Glu receptors outside the brain, in this review
I will outline our recent findings accumulated since then on the physiological
and pathological significance of neuronal amino acids as an extracellular signal
essential for homeostasis in a variety of phenotypic cells. In undifferentiated
neural progenitor cells, for instance, functional expression is seen with
different signaling machineries used for glutamatergic and GABAergic
neurotransmission in neurons. Moreover, Glu plays a role in mechanisms underlying
suppression of proliferation for self-replication in undifferentiated mesenchymal
stem cells. There is more accumulating evidence for neuronal amino acids playing
a role as an extracellular autocrine or paracrine signal commonly used in
different phenotypic cells. Evaluation of drugs currently used could be thus
beneficial for the efficient prophylaxis and/or the therapy of a variety of
diseases relevant to disturbance of amino acid signaling in diverse organs.
PMID- 26434097
TI - [Pain and emotional dysregulation: Cellular memory due to pain].
AB - Genetic factors are involved in determinants for the risk of psychiatric
disorders, and neurological and neurodegenerative diseases. Chronic pain stimuli
and intense pain have effects at a cellular and/or gene expression level, and
will eventually induce "cellular memory due to pain", which means that tissue
damage, even if only transient, can elicit epigenetically abnormal
transcription/translation and post-translational modification in related cells
depending on the degree or kind of injury or associated conditions. Such cell
memory/transformation due to pain can cause an abnormality in a fundamental
intracellular response, such as a change in the three-dimensional structure of
DNA, transcription, or translation. On the other hand, pain is a multidimensional
experience with sensory-discriminative and motivational-affective components.
Recent human brain imaging studies have examined differences in activity in the
nucleus accumbens between controls and patients with chronic pain, and have
revealed that the nucleus accumbens plays a role in predicting the value of a
noxious stimulus and its offset, and in the consequent changes in the
motivational state. In this review, we provide a very brief overview of a
comprehensive understanding of chronic pain associated with emotional
dysregulation due to transcriptional regulation, epigenetic modification and
miRNA regulation.
PMID- 26434098
TI - [Controlling sleep/wakefulness using optogenetics].
AB - Optogenetics is a recently developed experimental technique to control the
activity of neurons using light. Optogenetics shows its power to reveal the
physiological role of specific neural circuits in the brain. In particular,
manipulation of a specific type of neurons using optogenetics with high accuracy
timing enables us to analyze causality between neural activity and initiation of
animal behaviors. However, to manipulate the activity of specific neurons in
vivo, there are two critical steps to succeed in manipulation of the neural
activity and control of the behavior of individual animals. The first step is an
adequate number of molecules of light-activated protein that has to be expressed
in the cell membrane of the neurons of interest. The second step is the optical
system to illuminate the targeted neurons with enough intensity of light to
activate the light-activated protein. We applied optogenetics to hypothalamic
peptidergic neurons such as orexin/hypocretin neurons or melanin concentrating
hormone (MCH) neurons. These neurons are implicated in sleep/wakefulness
regulation. In this mini review, I will show the regulatory mechanism of
sleep/wakefulness by these neurons using optogenetics.
PMID- 26434099
TI - [Animals' clever adaptation strategy for seasonal changes in environment].
AB - Organisms living outside of tropical zones experience seasonal changes in
environment. Organisms are using day length as a calendar to change their
physiology and behavior such as seasonal breeding, hibernation, migration, and
molting. A comparative biology approach revealed underlying mechanisms of
vertebrate seasonal reproduction. Here we review the current understanding of
vertebrate seasonal reproduction. We Aso describe the involvement of tissue
specific post-translational modification in functional diversification of a
hormone.
PMID- 26434100
TI - Mid-term Results of Endovascular Treatment for Infrarenal Aortic Stenosis and
Occlusion.
AB - BACKGROUND: Focal stenosis or occlusion of the infrarenal aorta is rare, and
treatment is usually conventional bypass or endarterectomy. However, endovascular
treatment has advanced in recent years. The purpose of this retrospective study
is to report the results of primary stenting for focal infrarenal aortic
occlusive disease and clarify the usefulness of endovascular treatment. METHODS:
This study includes 6 consecutive patients (3 men, 3 women; mean age, 59.3 years)
with infrarenal aortic stenosis or occlusion who underwent endovascular
intervention at our hospital between April 2009 and February 2014. All patients
had bilateral intermittent claudication. The mean preoperative ankle-brachial
index (ABI) showed a slight to moderate decrease: right 0.668 and left 0.636. The
mean lesion site length was 12.5 mm, the percent stenosis was 90.7%, and
calcification was present in 3 patients. Primary stenting was performed in all
patients. The stent selected was generally a self-expanding stent (SES). For
patients with severe calcification, the stent selected was a balloon-expandable
stent (BES). RESULTS: Four patients received an SES and two patients received a
BES. The technical success rate was 100%, no complications occurred, and the mean
pressure gradient disappeared or decreased. Symptoms resolved in all patients and
the postoperative ABI improved: right 0.923 and left 0.968. During a mean follow
up period of 27 months, there were no recurrent symptoms and no restenosis on CT
angiography. CONCLUSIONS: Endovascular treatment should be considered as a first
line treatment for focal infrarenal aortic stenosis and occlusion.
PMID- 26434101
TI - Clinical Characteristics of Late Gadolinium Enhancement in Patients with Cardiac
Sarcoidosis.
AB - BACKGROUND: The presence of cardiac involvement in sarcoidosis, a multisystem
granulomatous disease of unknown etiology, is associated with very poor
prognosis. Therefore, early detection of cardiac sarcoidosis (C-sar) is very
important for effective treatment. Recently, the value of late gadolinium
enhancement (LGE) on cardiac magnetic resonance (CMR), which allows visualization
of even minute amounts of myocardial damage, has been emphasized in diagnosing C
sar. Although the presence of LGE has been added as a minor criterion for
diagnosing C-sar in the most recent Japan Ministry of Health and Welfare (JMHW)
guidelines, its clinical utility remains unknown. METHODS: A total of 17 patients
with biopsy-proven extracardiac sarcoidosis, who underwent CMR and examinations
using a sufficient number of modalities to diagnose or exclude C-sar in
accordance with the JMHW diagnostic criteria, were retrospectively enrolled in
this study. Among these 17 patients, 7 patients were diagnosed with C-sar and 10
with non-C-sar. We investigated the clinical performance of LGE in the detection
of cardiac involvement, compared the distribution of LGE with perfusion defects
of iodine-123-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) or
thallium-201 (201Tl) scintigraphy, and evaluated the prognostic value of LGE on
CMR in identifying adverse clinical events. RESULTS: All patients diagnosed with
C-sar were positive for LGE and all diagnosed with non-C-sar patients were
negative. Evaluation of LGE revealed a broader range of abnormalities than the
evaluation of the defects shown by either BMIPP or 201Tl scintigraphy. All
adverse events occurred in the C-sar patients with LGE. CONCLUSIONS: This study
showed that LGE is useful for the detection of cardiac involvement, and it might
be a promising tool for determining the prognosis of patients with biopsy-proven
extracardiac sarcoidosis.
PMID- 26434102
TI - Vascular Functional and Morphological Alterations in Smokers during Varenicline
Therapy.
AB - BACKGROUND: Varenicline has been reported to achieve high rates of smoking
cessation. It remains undetermined whether varenicline therapy improves vascular
function in smokers. METHODS: Consecutive Seventy-two smokers (age 57 +/- 12
years) who succeeded in complete smoking cessation and 46 normal healthy
volunteers (age 24 +/- 3 years) with no cardiovascular risk factors were enrolled
into this study. Vascular function and structure were assessed by flow-mediated
dilation (FMD), nitroglycerin-induced vasodilation, and brachial artery intima
media thickness (baIMT) at baseline and 20 weeks after the initiation of
varenicline therapy in smokers. FMD and baIMT were measured simultaneously using
a semi-automatic vessel wall-tracking software program. 75 MUg dose of a
nitroglycerin tablet were sublingually administered for the nitroglycerin-induced
vasodilation measurement. RESULTS: Exhaled-carbon monoxide concentration
decreased significantly (20.0 +/- 11.1 ppm at baseline vs 1.9 +/- 1.5 ppm after
20 weeks, p < 0.001). FMD was significantly improved after 20 weeks (4.09% +/-
1.83% at baseline vs 4.77% +/- 2.33% after 20 weeks, p = 0.010), whereas
nitroglycerin-induced vasodilation and baIMT were not significantly changed.
CONCLUSIONS: Smoking cessation with varenicline therapy significantly increased
FMD without significant changes of nitroglycerin-induced vasodilation or baIMT
from baseline to 20 weeks. It appears to improve vascular function in smokers,
which depends on endothelial function rather than on vascular smooth muscle
function or changes in vascular structure.
PMID- 26434103
TI - Percutaneous Carbon Dioxide Treatment Using a Gas Mist Generator Attenuates the
Development of Right Ventricular Dysfunction in Monocrotaline-induced Pulmonary
Hypertensive Rats.
AB - BACKGROUND: Highly concentrated carbon dioxide (GO2) is useful for treating
ischemic diseases. Therefore, we investigated whether treatment with a few
micrometers of CO2 molecules, atomized by two fluid nozzles (CO2 mist), could
attenuate the development of right ventricular (RV) dysfunction in pulmonary
hypertensive rats. METHODS: Six-week-old male Wistar rats were divided into three
groups: one that received injected saline; a second that received subcutaneous
monocrotaline (MCT; 60 mg/kg) without treatment (PH-UT) group; and a third that
received MCT with CO2 mist treatment (PH-CM) after MCT administration. The lower
body of each rat was encased in a polyethylene bag, filled with the designated
gaseous agent via a gas mist generator, for 30 minutes daily. Hemodynamics and
cardiac function were measured at 28 days after beginning MCT administration.
Protein levels were measured by western blotting. RESULTS: Rats that received MCT
without treatment began to die within 3-4 weeks of the initial administration.
However, treatment with CO2 mist extended the survival period of rats in that
group. At 28 days after MCT administration, the hemodynamic status, such as the
blood pressure and heart rate, involved with left ventricular function, of rats
in the PH-UT group were similar to those of rats in the PH-CM group. However, MCT
induced RV weight and RV dysfunction were significantly attenuated by treatment
with CO2 mist. Both RV phosphorylated endothelial nitric oxide synthase and heat
shock protein 72 levels increased significantly in the PH-CM group, compared to
the PH-UT group. CONCLUSIONS: Percutaneous CO2 mist therapy may alleviate RV
dysfunction in patients with pulmonary hypertension.
PMID- 26434104
TI - Pentraxin-3 as a Biomarker for Febrile Neutropenia in Patients with Lung Cancer.
AB - BACKGROUND: Pentraxin-3 (PTX3) is a newly discovered biomarker for various
inflammatory conditions. We measured plasma PTX3 levels in patients with febrile
neutropenic lung cancer and examined the utility of PTX3 levels as a biomarker
for febrile neutropenia. METHODS: Fourteen patients with febrile neutropenic lung
cancer were enrolled in the study. In addition, 10 untreated lung cancer patients
and 12 healthy adults were enrolled as a disease control group and a healthy
control group, respectively. On the day of onset of febrile neutropenia (day 1)
and days 3 and 7, PTX3 and C-reactive protein (CRP) levels were measured. In the
control groups, PTX3 and CRP levels were measured once. RESULTS: On day 1, plasma
CRP levels in febrile neutropenia during chemotherapy or chemoradiotherapy for
lung cancer (FN/LC) patients (8.11 +/- 6.42 mg/dL) were significantly higher than
those in healthy controls (HC) and chemotherapy/chemoradiotherapy-naive lung
cancer (CN/LC) patients (p < 0.05). However, CRP levels of the CN/LC group (0.33
+/- 0.02 mg/dL) were also significantly higher than those of the HC group (0.07
+/- 0.09 mg/dL) (p < 0.05). In contrast, plasma PTX3 levels of the FN/LC group
(6.14 +/- 5.28 ng/mL) were significantly higher than those of the HC and CN/LC
groups on day 1 (p < 0.05), but PTX3 levels of the CN/LC group (1.60 +/- 0.64
ng/mL) were not significantly higher than those of the HC group (1.05 +/- 0.25
ng/mL). In the FN/LC group, PTX3 levels peaked immediately on day 1. CONCLUSIONS:
PTX3 may be a useful biomarker for diagnosis of FN in patients with LC.
PMID- 26434105
TI - C-reactive Protein is a Useful Marker for Early Prediction of Anastomotic Leakage
after Esophageal Reconstruction.
AB - BACKGROUND: Esophageal anastomotic leakage is one of the most fatal complications
after esophagectomy and increases the hospitalization length. We aimed to
identify a convenient clinical marker of anastomotic leakage in the early
postoperative period. METHODS: In total, 108 patients who underwent esophagectomy
were retrospectively screened, and 96 were used to validate the overall results.
All 108 patients underwent physical examinations and determination of their white
blood cell count, C-reactive protein level, platelet count, fibrinogen level,
fibrin degradation product level, and antithrombin III level until postoperative
day 6. RESULTS: Anastomotic leakage occurred in 21 of the 108 patients (median
detection, 8 days). The C-reactive protein level on postoperative day 3 and
fibrinogen level on postoperative day 4 in the leakage group were significantly
higher than those in the nonleakage group. Receiver operating characteristic
curves for detection of anastomotic leakage were constructed; the cutoff value of
C-reactive protein on postoperative day 3 was 8.62 mg/dL, and that of fibrinogen
on postoperative day 4 was 712 mg/dL. Anastomotic leakage occurred in 23 of the
96 patients in the validation group. There was a significant difference between
the leakage and nonleakage groups when the C-reactive protein threshold on
postoperative day 3 was set at 8.62 mg/dL. However, there was no difference
between the groups when the fibrinogen threshold on postoperative day 4 was set
at 712 mg/dL. CONCLUSIONS: The C-reactive protein level on postoperative day 3 is
a valuable predictor of anastomotic leakage after esophagectomy and might allow
for earlier management of this complication.
PMID- 26434106
TI - Isolation of Monovalerianester A, an Inhibitor of Fat Accumulation, from
Valeriana fauriei.
AB - The rhizomes and roots of Valeriana fauriei were extracted with 80% aqueous
ethanol. This extract was found to exhibit potent inhibitory effects on fat
accumulation in 3T3-LI murine adipocytes. After several steps of chromatographic
purification, we succeeded in identifying monovalerianester A as an inhibitor of
fat accumulation. Thus, monovalerianester A and the crude extract of the rhizomes
and roots of V. fauriei may have therapeutic potential for the treatment of
obesity.
PMID- 26434107
TI - Arthropod Deterrents from Artemisia pallens (Davana Oil) Components.
AB - Davanone, a key sesquiterpene component of davana oil, has been synthesized in
five convenient steps. Oxygenated sesquiterpenes have been linked to insect
deterrent properties. Based on initial screening of davana oil, davanone and its
hydroxy precursors have been generated and are being evaluated as arthropod
deterrents against disease vectors.
PMID- 26434108
TI - Stereoselective Synthesis of 2,15-Dihydroxycalamenene and 2-Methoxycalamenene.
Determination of the Configuration of Natural 2,15-Dihydroxycalamenene.
AB - The enantioselective preparation of the two diastereoisomeric forms of 2,15
dihydroxycalamelene and 2-methoxycalamenene is here described. The (7S,10R) and
(7R,10R) isomers of these natural products were synthesized starting from (5R,8S)
methyl-4-hydroxy-8-isopropyl-5-methyl-5,6,7,8-tetrahydronaphthalene-2-carboxylate
and (5R,8R)-methyl-4-hydroxy-8-isopropyl-5-methyl-5,6,7,8-tetrahydronaphthalene-2
carboxylate, respectively, in turn preparable from (-)-menthone and (+)
isomenthone. The NMR analysis of the obtained sesquiterpenes allow assigning
(7R,10S) absolute configuration to the natural occurring 2,15
dihydroxycalamelene.
PMID- 26434109
TI - Sesquiterpenes from the Vietnamese Marine Sponge Dysidea fragilis.
AB - Two new sesquiterpenes, named dysinidins A-B (3, 4) along with two known
sesquiterpenes, furodysinin lactone (1) and O-methyl urodysinin lactone (2), were
isolated from the Vietnamese marine sponge Dysidea fragilis. Their structures
were determined by ID- and 2D-NMR spectroscopies and HR ESI MS, as well as by
comparison with reported literature data. None of compounds showed inhibitory
growth of human lung cancer cell lines, A-549 and H-1975 (IC50 > 30 MUM).
PMID- 26434110
TI - Vibrational Circular Dichroism Absolute Configuration of 9,12-Cyclomulin-13-ol, a
Diterpene from Azorella and Laretia Species.
AB - The absolute configuration of the diterpenoid 9,12-cyclomulin-13-ol (1), a
constituent of Azorella and Laretia species, has been established by vibrational
circular dichroism spectroscopy in combination with density functional theory
calculations. The obtained normal diterpene absolute configuration confirms that
of azorellanol (2), which was determined by single crystal X-ray diffraction.
PMID- 26434111
TI - Ultrafine Betulin Formulation with Biocompatible Carriers Exhibiting Improved
Dissolution Rate.
AB - The purpose of this research was to develop new methods of increasing dissolution
rate and solubility of betulin extracted from birch bark. The ultrafine
formulation of betulin with polyethylene glycol and beta-glycine was obtained by
freeze-drying. The rate of release of betulin from the formulation into water was
significantly higher in comparison with the initial betulin sample and its
composite with polyethylene glycol obtained by ball-milling.
PMID- 26434112
TI - Bio-assay Guided Isolation of Anti-cancer Compounds from Anthocephalus cadamba
Bark.
AB - Anthocephalus cadamba, an important plant in the traditional system of medicine
in India, is reported to possess anticancer activity. Guided by bio-assay tests
using human colorectal (HCT116) and hepatocellular carcinoma (HepG2) cell lines,
it has been shown to contain three active constituents, the triterpenoid saponins
3-O-[alpha-L-rhamnopyranosyl]-quinovic acid (1) and 3-O-[alpha-L-rhamnopyranosyl]
quinovic acid 28-O-[beta-D-glucopyranosyl] ester (2), and the alkaloid cadambine
(3). The structures of the isolated compounds were established using
spectroscopic techniques. The isolated compounds demonstrated concentration
dependent inhibition of both the cell lines, where compound 3 proved to be the
most potent inhibitor of cell line HCT116 (IC50 45 +/- 4 MUg/mL) and compound 2
demonstrated maximum inhibitory activity against HepG2 cell line with an IC50
value of 89 +/- 7 MUg/mL.
PMID- 26434113
TI - Damarane-type Saponins from Gynostemma longipes and their Cytotoxic Activity.
AB - Two new damarane-type saponins, named gylongiposides II-III (1 and 2), along with
one known compound, (23S)-3beta,20xi,21xi-trihydroxy-19-oxo-21,23-epoxydammar-24
ene 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[-D-xylopyranosyl-(1-->3)]-alpha-L
arabinopyranoside, were isolated from the leaves of Gynostemma longipes C.Y.Wu.
Their structures were determined by 1D- and 2D-NMR and HR-ESI-MS spectra.
Compounds 1-3 exhibited moderate activity against four human cancer cell lines, A
549, HT-29, OVCAR, and MCF-7, with IC50 values ranging from 9.8 +/- 2.1 to 49.6
+/- 2.6 MUM.
PMID- 26434114
TI - A New C23 Steroid from the Venom of Bufo bufo gargarizans.
AB - A new C23 steroid, (3beta,5beta,14beta)-methyl (3-hydroxy-14,15-epoxy-20-oxo-21
norcholan-24-oate) (1), together with four known ones (2-5), were isolated from
the venom of Bufo bufo gargarizans. Their structures were elucidated on the basis
of extensive spectroscopic analysis. The cytotoxicity of these compounds was also
evaluated against human hepatocarcinoma HepG2 cells. Compound 3 showed
significant cytotoxicity with an IC50 value of 16.8 +/- 0.7 MUM.
PMID- 26434115
TI - (-)-Pentylsedinine, a New Alkaloid from the Leaves of Lobelia tupa with Agonist
Activity at Nicotinic Acetylcholine Receptor.
AB - Lobelia tupa, also called devil's tobacco, is a native plant from the center
south of Chile which has been used by the native people of Chile as a
hallucinogenic and anesthetic plant. A new piperidine alkaloid, called
pentylsedinine, which comprises five carbons in the side chain, was isolated from
the aerial part of L. tupa, along with lobeline and lobelanidine. The structure
was established on the basis of 1D and 2D NMR spectroscopy. While lobeline is a
neutral antagonist at alpha3beta2/alpha3beta4 nAChR and alpha7 nAChR, both
lobelanidine and pentylsedinine act as partial agonists at nAChR.
PMID- 26434116
TI - Furoquinoline Alkaloids from the Leaves of Evodia lepta as Potential
Cholinesterase Inhibitors and their Molecular Docking.
AB - Nine furoquinoline alkaloids (1-9) were isolated from the leaves of Evodia lepta
based on bioassay-guided fractionation and chromatographic techniques. All
isolates were evaluated for their cholinesterase (ChEs) inhibitory activities, in
which kokusaginine (7) and melineurine (5) exhibited the highest activity toward
AChE and BChE, respectively. Lineweaver-Burk plots indicated that 5 and 7 were
mixed mode inhibitors of both ChE enzymes. Molecular docking studies on the
binding sites of AChE and BChE were performed in order to afford a molecular
insight into the mode of action of these active compounds. From this study these
compounds have emerged as promising molecules for Alzheimer's disease therapy.
PMID- 26434117
TI - Asperginine, an Unprecedented Alkaloid from the Marine-derived Fungus Aspergillus
sp.
AB - Asperginine (1), an alkaloid possessing a rare skeleton, was isolated from the
cultural broth of the marine fungus Aspergillus sp. (Z-4) isolated from the gut
of the marine isopod Ligia oceanica. The planar structure and relative
configuration of 1 was determined by analysis of NMR and mass spectral data. Its
absolute configuration was elucidated by Marfey's method, together with NOESY
correlations of key hydrogen atoms. The cytotoxicity against prostate cancer PC3
and human HCT116 was assayed by the MTT method. Unfortunately, asperginine did
not show any activity.
PMID- 26434118
TI - Effect of Quercetin on Cell Cycle and Cyclin Expression in Ovarian Carcinoma and
Osteosarcoma Cell Lines.
AB - Resistance to chemotherapeutic drugs is a major problem in cancer treatment. The
search for new interventions able to overcome this resistance may involve
compounds of natural origin, such as flavonoids, ubiquitously present in many
foods. In the present study, the cytotoxic effects and cell cycle modulation of
the flavonoid quercetin were investigated in ovarian carcinoma (SKOV3) and
osteosarcoma (U2OS) human cell lines and in their cisplatin (CDDP)-resistant
counterparts (SKOV3/CDDP and U2OSPt cells, respectively). Quercetin (10-50 MUM)
caused evident changes in the distribution of cell cycle phases in the CDDP
resistant SKOV3/CDDP ovarian cell line. The levels of cyclin D1 and cyclin B1
were determined by means of Western blot in all cell lines incubated with
quercetin (50 MUM) for 48 hours. The cyclin D1 expression was significantly
decreased following the treatment with quercetin in SKOV3 and U2OSPt cells, but
not in SKOV3/CDDP and U2OS cells. The reduction of cyclin D1 level could be
linked to the G1/S phase alteration found in quercetin-treated cells. Although
cyclin B1 is required for G2/M phase, and despite our observation that quercetin
influenced the G2/M phase of cell cycle, the flavonoid did not affect cyclin B1
levels in all cell lines, indicating the involvement of other possible
mechanisms. These results suggest that quercetin, exceeding the resistance to
CDDP, might become an interesting tool to evaluate cytotoxic activity in
combination with chemotherapy drugs.
PMID- 26434119
TI - Anti-Helicobacter pylori Activity of Four Alchemilla Species (Rosaceae).
AB - The present study evaluated the anti-Helicobacterpylori activity of Alchemilla
glabra Neygenf. (A. sect. Alchemilla), A. monticola Opiz (A. sect. Plicatae S.E.
Frohner), A. fissa Gunther & Schummel (A. sect. Calycinae (Buser) Buser) and A.
viridiflora Rothm. (A. sect. Calycinae), and identified ellagic acid and
quercetin-3-O-beta-glucoside. Anti-H. pylori activity was tested against ten
clinical isolates and one reference strain (ATCC 43504). The methanol extracts
were more active than the dichloromethane and cyclohexane extracts. The ranges of
concentrations were between 4 MUg/mL for methanol extracts of A. viridiflora, A.
glabra and A. monticola, and 256 MUg/mL for cyclohexane extracts of A.
viridiflora, A. glabra and A. fissa. The best overall activity was obtained with
A. monticola extracts. No significant difference was found in the ellagic acid
contents of the methanol extracts of the tested Alchemilla species (0.2-0.3
mg/mL), and anti-H. pylori activity was similar (4-32 MUg/mL). Ellagic acid
exhibited strong activity at very low concentrations (0.125-0.5 MUg/mL), while
the second identified compound, quercetin-3-O-beta-D-glucoside, was also very
active in concentration of 2-16 MUg/mL.
PMID- 26434120
TI - Peracylated Glucosyl Kaempferols from Pasania dodonfifolia Leaf.
AB - Phytochemical investigation of the ethanolic extract of Pasania dodoniifolia leaf
led to the isolation of four kaempferol 3-0-peracylated glucosides (1-4),
together with four flavonoid glucosides (5-8), epicatechin (9), and (7S, 7'S, 8R,
8'R)-icariol A2 (10). Of these, kaempferol-3-O-(3",4"-di-O-acetyl-2"-O-(Z)-p-
coumaroyl)-6"-O-(E)-p-coumaroyl)-beta-glucopyranoside (3) and 3-O-(3",4"-di-O
acetyl-2",6"-di-O-(Z)-p-coumaroyl)-beta-glucopyranoside (4) are new and their
structures were elucidated by 2D NMR spectroscopic analyses and MS data.
PMID- 26434121
TI - 6-Methoxyflavonol Glycosides with In Vitro Hepatoprotective Activity from
Chenopodium bonus-henricus Roots.
AB - One new, namely 6-methoxykaempferol 3-O-[beta-apiofuranosyl(l-->2)]-f
glucopyranosyl(l->6)-fl-glucopyranoside (2), and two known flavonoid glycosides,
spinacetin 3-O-[beta-apiofuranosyl(1-->2)]-beta-glucopyranosyl(1-->6)-beta
glucopyranoside (1) and spinacetin 3-O-gentiobioside (3), were isolated from the
roots of Chenopodium bonus-henricus L. Their structures were determined by means
of spectroscopic methods (ID, 2D NMR, UV, IR) and HR-ESI-MS. Radical scavenging
and anti-oxidant activities of 1 and 3 were established using DPPH and ABTS free
radicals, FRAP assay and inhibition of lipid peroxidation (LP) in a linoleic acid
system by the ferric thiocyanate method. Compound 3 was found to possess stronger
DPPH and ABTS radical scavenging activity (IC50 0.44 +/- 0.008 mM and 0.089 +/-
0.002 mM, respectively) compared with 1 (IC50 1.22 +/- 0.0 10 mM and 0.11 +/-
0.004 mM, respectively). Both flavonoids inhibited the lipid peroxidation of
linoleic acid significantly. Additionally, 1 and 3 significantly reduced the
cellular damage caused by the hepatotoxic agent CCI4 in rat hepatocytes and
preserved cell viability and GSH level, decreased LDH leakage and reduced lipid
damage. Effects were similar to those of the positive control silymarin. Control
of self-toxic effects made in a MTT based assay using HepG2 cells revealed
statistically significant cytotoxic effects only in very high concentrations
(exceeding mM) and an incubation time of 72 h, making flavonoid glycosides with a
6-methoxykaempferol skeleton a promising and safe class of hepatoprotective
compounds.
PMID- 26434122
TI - Flavonol Glycosides from the Leaves of Allium macrostemon.
AB - Twelve flavonoids were isolated from Allium macrostemon leaves. Five compounds
were identified as kaempferol 3,7-di-O-glucoside (1), kaempferol 3,4'-di-O
glucoside (2), quercetin 3-O-glucoside (3), kaempferol 3-0-glucoside (4) and
isorhamnetin 3-O-glucoside (5) by UV spectra, LC-MS, acid hydrolysis and HPLC
comparisons with authentic standards. Other flavonoids were characterized as
kaempferol glycosides (6-8, 10 and 11) and quercetin glycosides (9 and 12). Other
compounds, such as steroidal saponins, have been already found from the bulbs of
A. macrostemon. However, flavonoids were reported for the first time from the
leaves.
PMID- 26434123
TI - HPLC Plasma Assay of a Novel Anti-MRSA Compound, Kaempferol-3-O-Alpha-L-(2",3"-di
p-coumaroyl)rhamnoside, from Sycamore Leaves.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is a serious pathogen that is
resistant to current antibiotic therapy. Thus, there is an urgent need for novel
antimicrobial agents that can effectively combat these new strains of drug
resistant "superbugs". Recently, fractionation of an extract from Platanus
occidentalis (American sycamore) leaves produced an active kaempferol molecule, 3
O-alpha-L-(2",3"-di-p-coumaroyl)rhamnoside (KCR), in four isomeric forms; all
four isomers exhibit potent anti-MRSA activity. In order to further the
preclinical development of KCR as a new antibiotic class, we developed and
validated a simple analytical method for assaying KCR plasma concentration.
Because KCR will be developed as a new drug, although comprising four
stereoisomers, the analytical method was devised to assay the total amount of all
four isomers. In the present work, both a plasma processing procedure and an HPLC
method have been developed and validated. Mouse plasma containing KCR was first
treated with ethanol and then centrifuged. The supernatant was dried, suspended
in ethanol, centrifuged, and the supernatant was injected into an HPLC system
comprising a Waters C18, a mobile phase composing methanol, acetonitrile, and
trifluoroacetic acid and monitored at 313 nm. The method was validated by
parameters including a good linear correlation, a limit of quantification of 0.27
microg/mL, and high accuracy. In summary, this method allows a rapid analysis of
KCR in the plasma samples for pharmacokinetics studies.
PMID- 26434125
TI - Prenylhydroquinone-Derived Secondary Metabolites from Cultures of the
Basidiomycete Lentinus similis BCC 52578.
AB - Two new prenylhydroquinone-derived compounds, Ientinospirol (1) and 1-(2,5
dihydroxyphenyl)-4-hydroxy-3-methyl-l-butanone (2), were isolated from cultures
of the basidiomycete Lentinus similis BCC 52578, together with the known
compounds panepoxydone (3), panepoxydione (4), isopanepoxydone (5), 2,2-dimethyl
6-hydroxy-2H-chromene (6), and (3R,4S)-3,4-dihydroxy-2,2-dimethyl-6
methoxychroman (7). Compounds 3 and 4 exhibited cytotoxicity against all cell
lines tested, while the other compounds were inactive.
PMID- 26434124
TI - Biological Activity of Dolichandrone serrulata Flowers and Their Active
Components.
AB - Dolichandrone serrulata (DC.) Seem flowers are widely used as vegetables in
northern and eastern Thailand. Biological studies of the methanolic extract of
these flowers have shown promising antioxidant activity. Biological-guided
separation of D. serrulata flowers yielded six compounds, identified as
hallerone, protocatechuic acid, rengyolone, cleroindicin B, ixoside, and
isomaltose. This is the first report on hallerone, protocatechuic acid,
rengyolone, cleroindicin B, and isomaltose in D. serrulata. Protocatechuic acid
was the most potent scavenger of 2,2-diphenyl-l-picrylhydrazyl and hydroxyl
radicals with IC50 values of 25.6 +/- 0.6 and 29.6 +/- 0.4 microM, respectively.
Hallerone and rengyolone showed moderate scavenging action on superoxide radicals
and inhibited H202 induced reactive oxygen species production in HEK-293 cell. In
addition, the other isolated compounds showed weak activity.
PMID- 26434126
TI - Effects of Thymoquinone on the Pharmacokinetics and Pharmacodynamics of
Glibenclamide in a Rat Model.
AB - Glibenclamide and thymoquinone plasma concentrations were analysed using a
sensitive RP-HPLC method, and non-compartmental model pharmacokinetic parameters
were calculated. The maximum reduction in blood glucose level was observed 3
hours following glibenclamide administration, which reached 47.4% of baseline,
whereas it was reduced by 53.0% to 56.2% when co-administrated with thymoquinone.
Plasma concentration of glibenclamide was increased by 13.4% and 21.8% by the co
administration of thymoquinone as single and multiple doses, respectively
(P<0.05). The AUC and TI/2 of glibenclamide were also increased respectively by
32.0% and 17.4% with a thymoquinone single dose, and by 52.5% and 92.8% after
chronic treatment. Furthermore, diabetic rats treated with thymoquinone
demonstrated a marked decrease in hepatic protein expressions of CYP3A2 and CYP2C
11 enzymes that are responsible for the metabolism of glibenclamide. The current
data suggest that thymoquinone exhibits a synergistic effect with glibenclamide
on glucose level, which could be explained by reducing CYP450 activity at the
protein level.
PMID- 26434127
TI - Antioxidant and Antiinflammatory Compounds in Nutmeg (Myristicafragrans) Pericarp
as Determined by in vitro Assays.
AB - Nutmeg, Myristicafragrans, is known for its culinary and medicinal values. The
nutmeg pericarp, abundant during the production of the seed, is also used in food
and beverage preparations. In this study, the pericarp of M. fragrans was
evaluated for its bioactive components using in vitro antioxidant and
antiinflammatory assays. The hexane, ethyl acetate and methanolic extracts
inhibited lipid peroxidation (LPO) by 82.5, 70.1 and 73.2%, and cyclooxygenase
enzymes COX-1 by 44, 44 and 42% and COX-2 by 47, 41 and 36%, respectively, at 100
microg/mL. The bioassay-guided purifications of extracts yielded 20 compounds
belonged to neolignans (0.13%), phenylpropanoids (0.28%), phenolic aldehyde
(0.35%), triterpenoids (0.06%), triglycerides (0.20%), sugars (10.2%) and
steroids (0.49%). Pure isolates 1-5 inhibited LPO by 70-99% and 3-12 inhibited
COX-1 and -2 enzymes by 37-49%. This is the first report on the bioassay-guided
characterization of constituents in nutmeg pericarp. Our results support the
medicinal claims of nutmeg pericarp.
PMID- 26434128
TI - In Vitro Safety/Protection Assessment of Resveratrol and Pterostilbene in a Human
Hepatoma Cell Line (HepG2).
AB - The aim of this work was to evaluate in vitro the genotoxic and/or antigenotoxic
effects of resveratrol (RESV) and pterostilbene (PTER) on HepG2 cells. Moreover,
additional tests were performed to evaluate early and late apoptosis events
induced by the tested stilbenes. RESV and PTER did not show any genotoxic
activity. As regards antigenotoxicity testing, RESV and PTER showed a typical, U
shaped hormetic dose-response relationship characterized by a biphasic trend with
small quantities having opposite effects to large ones. HepG2 cells treated with
PTER exhibited a marked increase in early apoptosis (40.1%) at 250 microM;
whereas, the highest concentration tested for both RESV and PTER significantly
increased the proportion of HepG2 cells undergoing late apoptosis (32.5 and
51.2%, respectively). The observed pro-apoptotic activity could, at least in
part, explain the hormetic response observed when the compounds were tested for
antigenotoxicity (i.e., in the presence of induced DNA damage).
PMID- 26434129
TI - Red Maple (Acer rubrum) Aerial Parts as a Source of Bioactive Phenolics.
AB - The bark and stems of red maple (Acer rubrum) are reported to contain bioactive
phenolics but its aerial parts, namely, flowers and leaves, remain largely
unexplored. This is unfortunate considering that various parts of the red maple
were used for traditional medicinal purposes by the indigenous peoples of eastern
North America, where this species is found. Herein, we report the identification
of twenty-five (1-25) phenolics, including two new galloyl derivatives (1 and 2),
from red maple flowers and leaves. Of these, ten compounds (1-10), including the
new compounds, were isolated and identified by NMR and HRESIMS data while the
remaining fifteen compounds (11-25) were identified by HPLC-DAD analyses (by
comparison with chemical standards). The isolates (1-10), along with the clinical
drug, acarbose, were evaluated for their alpha-glucosidase enzyme inhibitory
activities.
PMID- 26434130
TI - Changes in the Content of the Glycosides, Aglycons and their Possible Precursors
of Rhodiola rosea during the Vegetation Period.
AB - Phytochemical participants in the biosynthetic pathway of salidroside and
cinnamyl alcohol glycosides were studied from seven Rhodiola rosea L. individuals
originating from a wild population. Plants were grown in a phytotron and samples
were taken at 3 weekly intervals during the vegetation period. Based on HPLC
analysis, all the key compounds to which roseroot medicinal property is
attributed were detected, with salidrosde being the most dominant, followed by
its aglycone, tyrosol. The contents of all compounds were 2-3 times more in the
rhizomes than in roots. The highest content of salidroside, tyrosol, rosarin,
rosavin and cinnamyl alcohol was recorded in rhizomes and at the beginning of
shoot elongation. The seven roseroot individuals showed a very high deviation in
their chemical content at each sampling time. Our statistical analysis showed
that the trend of salidroside accumulation in the rhizome was the most similar in
all studied plants. These results have important implications for choosing a
reasonable harvest time to obtain the maximum phytochemical content and a better
understanding of active compounds formation in R. rosea L.
PMID- 26434131
TI - Biocompounds Attenuating the Development of Obesity and Insulin Resistance
Produced by a High-fat Sucrose Diet.
AB - The use of biocompounds as agents with potential anti-obesity effects might be a
feasible alternative to the prescription of traditional drugs in the near future.
The goal of the present study was to screen five different compounds in relation
to their ability to prevent body weight gain and ameliorate obesity-associated
metabolic impairments, namely insulin resistance. For this purpose, seventy
Wistar rats were randomly assigned into seven experimental groups. A standard
diet-fed control group (control, n=10); a high-fat, high-sucrose diet-fed group
(HFS, n=10) and five experimental groups which were fed the HFS diet supplemented
with one of the following biocompounds; curcumin (100 mg/kg bw, n=10),
chlorogenic acid (50 mg/kg bw, n=10), coumaric acid (100 mg/kg bw, n=10),
naringin (100 mg/kg bw, n=10) and leucine (1% of diet, n=10). These results
confirm the effectiveness of all the compounds to reduce significantly food
efficiency, despite the significant higher food intake. Moreover, visceral fat
mass percentage was significantly decreased after naringin and coumaric acid
supplementation. In fact, this finding might be related to the considerable
amelioration of HOMA-IR index detected in naringin-treated animals. A significant
reduction in serum insulin levels and an improvement in the intraperitoneal
glucose tolerance test and AUC were found in leucine- and coumaric acid-treated
rats, respectively. In summary, the tested biocompounds, particularly naringin,
coumaric acid and leucine, showed potential benefits in the prevention of obesity
related complications in rats, at least at the proved doses.
PMID- 26434132
TI - A Novel C21 Cyclopentenone Derivative from Cipadessa cinerascens.
AB - A new C21 cyclopentenone derivative, Cipacyclonone (1), was isolated from the
leaves of Cipadessa cinerascens. Its structure was elucidated on the basis of
spectroscopic analysis, including extensive 1D- and 2D-NMR techniques. Compound 1
showed strong cytotoxicity activity against HL-60 and A-549 cell lines, with IC50
values of 1.2 and 3.0 microM, respectively.
PMID- 26434133
TI - Effects on MC3T3-E1 Cells and In silico Toxicological Study of Two 6-(Propan-2
yl)-4-methyl-morpholine-2,5-diones.
AB - Recently, we found that two cyclodidepsipeptides, 3,6-di-(propan-2-yl)-4-methyl
morpholine-2,5-dione (1) and 3-(2-methylpropyl)-6-(propan-2-yl)-4-methyl-
morpholine-2,5-dione (2), are excellent inhibitors of xanthine oxidase. In order
to obtain more information about the toxicological potential of compounds 1 and 2
on bone cells, the current study was designed to evaluate the effect of these
compounds on viability and proliferation of MC3T3-E1 cells. Compound 1 showed
neither cytotoxic nor stimulatory effect on cell viability, while compound 2
showed a slight stimulatory effect on cell viability. Both studied compounds
showed slight stimulatory effects on proliferation of MC3T3-E1 cells, in a dose
dependent manner. Additionally, an in silico toxicological study of compounds 1
and 2 was performed, and the results indicate that they have a good probability
of safe biological intake.
PMID- 26434134
TI - Release of Antioxidant Peptides from the Body Wall Proteins of the Sea Cucumber
Isostichopus fuscus.
AB - Proteases from the tentacles of the sea cucumber Isostichopusfuscus were
partially purified and used to produce antioxidant peptides from body wall
proteins of this marine species. Three proteins (105, 68, and 39 kDa) were
identified by SDS-PAGE in the proteolytic extract of the tentacles. Protein
hydrolyzates were generated with gelatin and crude protein substrates from body
wall, and peptidic fractions lower and higher than 3 kDa were obtained to
evaluate their oxygen radical scavenging capacity (ORAC). The 3 kDa-fraction
obtained from the crude protein hydrolyzate showed the highest ORAC value (0.92
+/- 0.04 micromol Trolox equivalent/mg protein). This fraction was selected to
purify peptides potentially responsible for the activity that might be used as
ingredients for development of functional foods.
PMID- 26434135
TI - Bioactivity-guided Separation of the Active Compounds in Acacia pennata
Responsible for the Prevention of Alzheimer's Disease.
AB - The objective of this study was to evaluate the health benefits of plants used in
Thai food, specifically Acacia pennata Willd., in Alzheimer's prevention. A.
pennata twigs strongly inhibited beta-amyloid aggregation. Bioactivity-guided
separation of the active fractions yielded six known compounds, tetracosane (1),
1-(heptyloxy)-octadecane (2), methyl tridecanoate (3), arborinone (4),
confertamide A (5) and 4-hydroxy-1-methyl-pyrrolidin-2-carboxylic acid (6). The
structures were determined by spectroscopic analysis. Biological testing revealed
that tetracosane (1) was the most potent inhibitor of beta-amyloid aggregation,
followed by 1-(heptyloxy)-octadecane (2) with IC50 values of 0.4 and 12.3 MUM.
Methyl tridecanoate (3), arborinone (4) and 4-hydroxy-1-methyl-pyrrolidin-2
carboxylic acid (6) moderately inhibited beta-amyloid aggregation. In addition,
tetracosane (1) and methyl tridecanoate (3) weakly inhibited acetylcholinesterase
(AChE). These results suggested that the effect of A. pennata on Alzheimer's
disease was likely due to the inhibition of beta-amyloid aggregation. Thus A.
pennata may be beneficial for Alzheimer's prevention.
PMID- 26434136
TI - Development and Validation of LC-MS/MS Method for Quantitative Determination of
Adenosine, Guanosine, Xanthine and Uric acid in Widely Consumed Vegetables in
Thailand.
AB - In this study, a triple quadrupole LC-MS/MS electrospray ionization method was
developed and validated for quantitative determination of adenosine, guanosine,
xanthine and uric acid in fifteen widely consumed Thai vegetables. The method was
successively developed by using caffeine as internal standard. The lower limit of
quantitation (LLOQ) was 0.2 MUg/g for adenosine and guanosine, and 1.0 MUg/g for
uric acid and xanthine. The method was fully validated according to USFDA
guidelines and all performance characteristics were found acceptable.
Subsequently, the developed and validated LC-MS/MS method was applied to
determine the four interest substances in fifteen widely consumed vegetables in
Thailand. The results showed that all vegetables included in the study could be
classified as low adenosine, guanosine, xanthine and uric acid containing foods
since the concentrations of these substances were less than 50 mg per 100 g. This
finding was enormously valuable information for hyperuricemia and gouty patients.
PMID- 26434137
TI - Chemical Composition of the Essential Oil from Chaerophyllum temulum (Apiaceae).
AB - The present study reports the chemical composition on the essential oil obtained
from fresh roots, stems, inflorescences and fruits of Chaerophyllum temulum. In
all samples, except the roots, the most dominant components were sesquiterpene
hydrocarbons. (Z)-Falcarinol was the principal constituent of the root essential
oils (61.7% at the flowering stage and 62.3% at the fruiting stage). The blossom
oil was dominated by (Z,E)-alpha-famesene (23.4%), (E)-beta-farnesene (9.0%) and
germacrene D-4-ol (9%), whereas the oil from the fruit had germacrene D-4-ol
(27.6%) as its main compound, accompanied by (Z,E)-alpha-famesene (13.4%).
Germacrene D was the most abundant component of the stem essential oil (38.4% at
the flowering stage and 32.5% at the fruiting stage). The obtained results show
that the qualitative composition of the oil depends on the part of the plant
which is analyzed, while the quantitative composition of the main components
depends on the growing stage of the plant.
PMID- 26434138
TI - Comparison of Essential Oils Obtained from Different Extraction Techniques as an
Aid in Identifying Aroma Significant Compounds of Nutmeg (Myristica fragrans).
AB - Distribution of volatile constituents in the essential oil of nutmeg obtained by
simultaneous distillation extraction (SDE), high vacuum distillation (HVD) and
super critical fluid extraction (SFE) was compared with reduced pressure
distillation (RPD) and head space (HS) analysis. HS and RPD volatiles were
characterized by a high content of sabinene, followed by alpha-pinene and beta
pinene. Interestingly, unlike the SDE, HVD and SFE oils, distillates from HS and
RPD were marked by the absence of phenolic ethers namely myristicin, elemicin and
safrole. The HS and RPD volatiles possessed a pleasant nutmeg aroma indicating a
significant role of terpenic constituents in contributing to the top aroma note.
GC-olfactometry (GC-O) of the oils aided in establishing the role of sabinene,
alpha-pinene and beta-pinene in contributing to the distinctive note of the
spice. A high odor activity value (OAV) of sabinene and alpha-pinene established
the role of these two constituents in imparting the characteristic nutmeg odor.
PMID- 26434139
TI - Chemical Variability of the Essential Oil Isolated from Aerial Parts of
Tetraclinis articulata from North-Western Algeria.
AB - The objective was to investigate the yield and chemical composition of 50
essential oil samples isolated from leaves and flowers of Tetraclinis articulata
harvested in eight locations (coastal township and highlands) of Tlemcen Province
(North-Western Algeria). Essential oil yields varied drastically from sample to
sample (0.03 to 0.86%, w/w). No direct correlation was observed between the yield
and the altitude of the harvest areas. The oils consisted mainly of monoterpenes:
alpha-pinene (9.2-56.5%), bornyl acetate (1.2-45.1%), camphor (0.5-40.3%),
borneol (0.2-12.9%), limonene (3.6-12.5%), and myrcene (1.6-9.7%). Sesquiterpenes
were represented by germacrene D (up to 14.2%) and (E)-beta-caryophyllene (up to
13.3%). PCA analysis of the data allowed the distinction of two groups within the
samples. The composition of group I (9 samples) was dominated by camphor, (Mean =
30.9%) followed by alpha-pinene (M = 19.1%) and bornyl acetate (M = 11.4%). Group
II was divided into two sub-groups. Samples of sub-group IIA (8 samples)
contained mainly alpha-pinene (M = 45.4%). Samples of the largest group IIB (33
samples) were characterized by similar contents of alpha-pinene (M = 28.2%) and
bornyl acetate (M = 24.5%) and the occurrence of camphor to a lesser extent (M =
10.0%).
PMID- 26434140
TI - Composition and Bioactivities of an (E)-beta-Farnesene Chemotype of Chamomile
(Matricaria chamomilla) Essential Oil from Nepal.
AB - The essential oil of Matricaria chamomilla, collected from Nepal, was obtained by
hydrodistillation and analyzed by gas chromatography-mass spectrometry. The major
components in Nepalese chamomile oil were (E)-beta-famesene (42.2%), alpha
bisabolol oxide A (22.3%), (E,E)-alpha-famesene (8.3%), cis-bicycloether (5.0%),
alpha-bisabolol oxide B (4.5%), and alpha-bisabolone oxide A (4.0%). A cluster
analysis based on the chemical compositions of 48 samples of chamomile oil
reported in the literature has revealed seven chemotypes, and the oil from Nepal
represents the (E)-beta-farnesene chemotype. The chamomile oil was screened for
antimicrobial activity against Bacillus cereus, Staphylococcus aureus,
Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Aspergillus
niger, and toxicity toward MCF-7 breast tumor cells, Artemia salina, Chaoborus
plumicornis, Caenorhabditis elegans, and Drosophila melanogaster.
PMID- 26434141
TI - Chemical Composition of the Essential Oil from Croton oblongifolius and its
Antibacterial Activity against Propionibacterium acnes.
AB - The essential oil of C. oblongifolius Roxb. stem bark was obtained by
hydrodistillation. Chemical analysis by GC-MS identified 29 compounds. Terpinen-4
ol (17.8%) was a major component, together with alpha-guaiene (7.9%), E
caryophyllene (7.0%), myrcene (6.7%), (+)-cyclosativene (5.1%), sabinene (4.8%),
aciphyllene (4.7%), pogostol (4.6%), gamma-terpinene (3.4%), alpha-muurolol
(3.2%) and germecrene D (3.2%). The essential oil exhibited antibacterial
activity against Propionibacterium acnes ATCC 6919 with an MIC of 0.125%, v/v.
PMID- 26434142
TI - Composition, in vitro Anti-inflammatory, Antioxidant and Antimicrobial Activities
of Essential Oils from Leaf and Twig Parts of Cupressus cashmeriana.
AB - The chemical composition and in vitro anti-inflammatory, antioxidant and
antimicrobial activities of the essential oils isolated from the leaf and twig of
Cupressus cashmeriana have been investigated. The essential oils were isolated
using hydrodistillation in a Clevenger-type apparatus, and characterized by GC
FID and GC-MS, respectively. The leaf oil mainly consisted of alpha-pinene
(21.8%), epizonarene (8.0%), sabinene (7.9%), limonene (7.6%), gamma-terpinene
(7.0%), and allo-aromadendrene (7.0%); the twig oil was mostly carvacrol methyl
ether (35.4%), manool (16.1%), carvacrol (14.2%), and (2Z,6E)-farnesol (6.9%).
Twig oil, but not leaf oil, was able to reduce nitric oxide production by
lipopolysaccharide-activated murine macrophages RAW 264.7 without reducing the
cell viability. In addition, twig oil showed better antioxidant and antimicrobial
activities than leaf oil. The major ingredient of the twig oil that was
responsible for the anti-inflammatory, antioxidant and antimicrobial activities
was carvacrol.
PMID- 26434143
TI - Antioxidant and Anticholinesterase Activities of Essential Oils of Cinnamomum
griffithii and C. macrocarpum.
AB - The essential oils of Cinnamomum griffithii and C. macrocarpum were analyzed by
GC and GC-MS and evaluated for their antioxidant and anticholinesterase
activities. The essential oils of leaf and bark of C. grffithii were
characterized by the presence of 30 components, with methyl eugenol (38.5-43.8%)
as the major component. A total of 11 components were characterized in.the leaf
and bark of C. macrocarpum essential oil with the most abundant component was
safrole (54.5-59.5%). The bark oil of C. griffithii demonstrated significant
activity on DPPH (IC50 73.4 microg/mL) and a high phenolic content (192.0%),
while the leaf oil inhibited oxidation of beta-carotene/linoleic acid with an
inhibition value of 65.5 MUg/mL. Acetylcholinesterase and butyrylcholinesterase
inhibition were assessed and the results showed that C. macrocarpun bark oil
exhibited significant activity with inhibition values of 55.8% and 66.1%,
respectively at a concentration of 1 mg/mL.
PMID- 26434144
TI - Essential Oil Composition and Antigermination Activity of Artemisia dracunculus
(Tarragon).
AB - The chemical composition of an Italian oil of tarragon (Artemisia dracunculus L.)
was analyzed by GC/EIMS. The major compound of the oil was estragole (73.3%),
followed by limonene (5.4%), (E)-beta-ocimene (5.3%), beta-pinene (3.4%) and (Z)
beta-ocimene (3.0%). The essential oil was tested "in vitro" for its
antigermination activity against Raphanus sativus L., Lepidium sativum L, Papaver
rhoeas L. and Avena fatua L. seeds and demonstrating a good inhibitory activity
in a dose-dependent way.
PMID- 26434145
TI - In Vitro Activity of Twenty Commercially Available, Plant-Derived Essential Oils
against Selected Dermatophyte Species.
AB - The in vitro activity of twenty chemically defined essential oils (EOs) obtained
from Boswellia sacra, Citrus bergamia, C. limon, C. medica, Cinnamomum
zeylanicum, Eucalyptus globulus, Foeniculum vulgare, Helichrysum italicum,
Illicium verum, Litsea cubeba, Mentha spicata, Myrtus communis, Ocimum basilicum,
Origanum majorana, O. vulgare, Pelargonium graveolens, Rosmarinus officinalis,
Santalum album, Satureja montana, and Thymus serpyllum was assayed against
clinical animal isolates of Microsporum canis, Trichophyton mentagrophytes, T.
erinacei, T. terrestre and Microsporum gypseum, main causative agents of zoonotic
and/or environmental dermatophytoses in humans. Single main components present in
high amounts in such EOs were also tested. Different dermatophyte species showed
remarkable differences in sensitivity. In general, more effective EOs were T.
serpyllum (MIC range 0.025%-0.25%), O. vulgare (MIC range 0.025%-0.5%) and L.
cubeba (MIC range 0.025%-1.5%). F. vulgare showed a moderate efficacy against
geophilic species such as M gypseum and T terrestre. Among single main components
tested, neral was the most active (MIC and MFC values 5 0.25%). The results of
the present study seem to be promising for an in vivo use of some assayed EOs.
PMID- 26434146
TI - Intracerebral Distribution of a-Pinene and the Anxiolytic-like Effect in Mice
Following Inhaled Administration of Essential Oil from Chamaecyparis obtuse.
AB - The anxiolytic-like and stress reduction effects following inhaled administration
of essential oil from Chamaecyparis obtusa (EOCO) have been reported. Volatile
components are thought to produce these effects of EOCO by neurological transfer
and pharmacological transfer. The regions of the brain in which inhaled compounds
are found due to pharmacological transfer of EOCO are not known. This research
was undertaken to clarify the relationship between the intracerebral distribution
of alpha-pinene, which is the main component of EOCO, and emotional behavior.
alpha-Pinene was detected as the main component of volatile EOCO. The amount of
alpha-pinene in each region of the brain was measured following inhaled
administration of EOCO. The amount of alpha-pinene was different in each region
of the brain. With inhaled administration of 32 MUL/L air EOCO, a high
concentration of alpha-pinene was observed. However, no significant differences
in the concentration of alpha-pinene among brain regions were found. A
therapeutic concentration of alpha-pinene (8 MUL/L air EOCO) in each region of
the brain may induce an anxiolytic-like effect, and a high concentration of alpha
pinene (32 MUL/L air EOCO) in each region of the brain may induce an excitatory
like effect. The increases in the concentration of alpha-pinene from 8 to 32
MUL/L air EOCO in the striatum and the hippocampus were significantly lower
compared with the increases in other brain regions. These results indicate that
regions besides the striatum and the hippocampus participated in the increase in
locomotor activity due to the high concentration of alpha-pinene in the brain.
PMID- 26434147
TI - A Comprehensive Review of the Cosmeceutical Benefits of Vanda Species
(Orchidaceae).
AB - Orchidaceae is the largest family of flowering plants with over 35,000 species
and 850 genera. About 3300 species of orchids are found in Malaysia and the
diversity is highest in the Main, Keledang, Bintang and Tahan Ranges. Apart from
being prized for their beauty, orchids have long been used by humans for
medicinal purposes. Today the uses of orchids have been expanded to the food and
cosmetics industries. Many cosmeceutical companies use orchid extracts as an
active ingredient in their products. Previous studies provide riveting insights
into the potential uses of orchid extracts as an active agent in cosmetics. This
paper describes the cosmeceutical potential of orchids as an anti-aging, and skin
moisturizing agent. Orchid extracts from Vanda coerulea and V. teres delay aging
caused by reactive oxygen species (ROS) following LV irradiation through their
antioxidant and anti-inflammatory activity. These extracts also show anti-aging
properties by stimulating cytochrome c oxidase (complex IV), which is part of the
electron transport chain in mitochondria. Stimulation of cytochrome c oxidase
improves the respiratory function of mitochondria in keratinocytes. The presence
of mucilage in orchids enables them to maintain skin hydration. Mucilage
functions as a moisturizer and emollient due to its high water binding capacity.
Additionally, orchid extracts provide skin hydration by stimulating aquaporin 3
(AQP3) and LEKTI protein expression. The presence of AQP3 leads to a five-fold
increase in water permeability, which subsequently increases stratum corneum
hydration. Increased LEKTI protein expression mediated by orchid extracts reduces
the degradation of desmoglein-1 and enhances the structural function of
desmosomes, which play important roles in preventing water evaporation.
PMID- 26434148
TI - Genotoxicity and Antigenotoxicity Studies of Traditional Medicinal Plants: How
Informative and Accurate are the Results?
AB - Genotoxicity and antigenotoxicity studies of (traditional medicinal) plants are
important from a risk assessment point of view and in the search for new
medication against, for example, cancer. It is clear yet that attention should be
paid to a number of aspects that may influence the outcome of a study and to
which often no or insufficient attention is paid. A short overview is given of
such aspects that deserve more attention.
PMID- 26434149
TI - Bodil Schmidt-Nielson (1918-2015) 48th APS President.
PMID- 26434150
TI - How Diversity is Becoming a Reality in the American Physiological Society.
PMID- 26434151
TI - Off the Grid.
PMID- 26434153
TI - Cuban and American Physiological Societies Sign Historic Agreement for Research
Collaboration.
PMID- 26434154
TI - APS, FASEB Highlight Role of Professional Societies in Annual Postdoc Meeting.
PMID- 26434155
TI - Serving Our Society.
PMID- 26434156
TI - APSselect: Year One a Success!
PMID- 26434157
TI - APS Suggests Ways for USDA to Reduce Regulatory Burden.
PMID- 26434158
TI - Congress Introduces Authorizing Legislation for NIH, NSF.
PMID- 26434159
TI - The W's of Networking in Physiology.
PMID- 26434160
TI - Response to "Bias is Stagnating Physiology".
PMID- 26434161
TI - Impact Factors.
PMID- 26434162
TI - FOREWORD. Ninety years ago, Raymond Pearl, a professor of biology at Johns
Hopkins University.
PMID- 26434163
TI - HEALTH SELECTION THEORY: AN EXPLANATION FOR THE PARADOX BETWEEN PERCEIVED MALE
WELL-BEING AND MORTALITY.
AB - Paradoxically, men report better health and quality of life than women, but men
experience higher mortality rates than women at most ages. One conclusion from
these findings is that men have been selected to disregard signs of ill health,
or even to deceive themselves about their health, to their detriment because
presenting themselves as healthy has fitness benefits. We hypothesize that men
have been sexually selected to present themselves to women as healthy but that
the cost of not attending to their minor health problems results in earlier
mortality than women. We present a review of the human and primate literature
that supports health selection theory, the hypothesis that females have
preferentially selected males who present themselves as healthy.
PMID- 26434164
TI - ECOLOGICAL AND EVOLUTIONARY APPLICATIONS FOR ENVIRONMENTAL SEX REVERSAL OF FISH.
AB - Environmental sex reversal (ESR), which results in a mismatch between genotypic
and phenotypic sex, is well documented in numerous fish species and may be
induced by chemical exposure. Historically, research involving piscine ESR has
been carried out with a view to improving profitability in aquaculture or to
elucidate the processes governing sex determination and sexual differentiation.
However, recent studies in evolution and ecology suggest research on ESR now has
much wider applications and ramifications. We begin with an overview of ESR in
fish and a brief review of the traditional applications thereof. We then discuss
ESR and its potential demographic consequences in wild populations. Theory even
suggests sex-reversed fish may be purposefully released to manipulate population
dynamics. We suggest new research directions that may prove fruitful in
understanding how ESR at the individual level translates to population-level
processes. In the latter portion of the review we focus on evolutionary
applications of ESR. Sex-reversal studies from the aquaculture literature provide
insight in to the evolvability of determinants of sexual phenotype. Additionally,
induced sex reversal can provide information about the evolution of sex
chromosomes and sex-linked traits. Recently, naturally occurring ESR has been
implicated as a mechanism contributing to the evolution of sex chromosomes.
PMID- 26434165
TI - REWRITING ECOLOGICAL SUCCESSION HISTORY: DID CARRION ECOLOGISTS GET THERE FIRST?
AB - Ecological succession is arguably the most enduring contribution of plant
ecologists and its origins have never been contested. However, we show that
French entomologist Pierre Megnin, while collaborating with medical examiners in
the late 1800s, advanced the first formal definition and testable mechanism of
ecological succession. This discovery gave birth to the twin disciplines of
carrion ecology and forensic entomology. As a novel case of multiple independent
discovery, we chronicle how the disciplines of plant and carrion ecology
(including forensic entomology) accumulated strikingly similar parallel histories
and contributions. In the 1900s, the two groups diverged in methodology and
purpose, with carrion ecologists and forensic entomologists focusing mostly on
case reports and observational studies instead of hypothesis testing. Momentum is
currently growing, however, to develop the ecological framework of forensic
entomology and advance carrion ecology theory. Researchers are recognizing the
potential of carcasses as subjects for testing not only succession mechanisms
(without assuming space-for-time substitution), but also aggregation and
coexistence models, diversity-ecosystem function relationships, and the dynamics
of pulsed resources. By comparing the contributions of plant and carrion
ecologists, we hope to stimulate future crossover research that leads to a
general theory of ecological succession.
PMID- 26434166
TI - Telemedicine: The Physician's Double-Edged Sword.
PMID- 26434167
TI - Indigenous Cases of Leprosy (Hansen's Disease) in Southern Mississippi.
AB - Hansen's disease or leprosy is a chronic infection of the skin and peripheral
nerves caused by Mycobacterium leprae. In the U.S., leprosy is mainly reported in
immigrants, but indigenous leprosy cases have been also reported in this country,
especially in semitropical southern states (i.e., Texas, Louisiana). The
objective of this series of cases is to describe indigenous leprosy cases
reported in southern Mississippi (MS) during the period 2012-2014. Information
was collected from medical records at Hattiesburg Clinic and the MS Department of
Health. Four cases were reported during the period of study (3 Caucasian males, 1
African-American woman). Non of visited endemic leprosy country. The age ranged
from 60 to 83 years (median: 75.5 years). Of the four cases, three presented with
a slowly progressive erythematous rash disseminated mainly on the thorax and
abdomen, with a lesser degree on the extremities. The time between onset of rash
until the diagnosis ranged from 5 to 16 months (median: 7 months). Only one case
had direct contact with armadillos (blood exposure). Non of these patients had a
history of immunosuppression. The most common symptoms were neuropathic pain
(n=2), generalized pruritus (n=2) and loss of sensation in extremities (n=2). One
case had severe peripheral neuropathy with muscle weakness, atrophy in left arm,
and wasting on left hand. Skin biopsies showed diffuse granulomatous infiltrate
with foamy histiocytes along with acid fast bacilli by Fite stain. By Ridley
Jopling classification system, three cases were diagnosis as lepromatous leprosy,
and one, borderline lepromatous. Treatment included clofazimine, dapsone and
rifampin that was offered free of charge by the National Hansen's Diseases
Program, Baton Rouge, L.A. One patient did not tolerate therapy. In conclusion, a
slowly progressive disseminated erythematous skin rash on the trunk should raise
suspicion for leprosy in the elderly population in south MS.
PMID- 26434168
TI - Beyond Respiratory Depression and Constipation: Adverse Effects of Opioids.
AB - The numbers of opioid presciptions have skyrocketed over the last two decades.
Adverse effects of opioids are difficult to diagnose because the usual presenting
complaints is persistence of severe pain and decreases function leading to
chronic usage of medication with minimal benefit to patients. This concise review
discusses the adverse effects of opioids to appropriately diagnose and treat
patients on opioid therapy. We emphasize less commonly known adverse effects and
the controversial use of opioids in non-cancer pain.
PMID- 26434169
TI - Top Ten Facts You Need to Know about Medical Emergencies While Flying.
PMID- 26434170
TI - Two New Members Appointed to the State Board of Health.
PMID- 26434172
TI - On Match Day, Suspense Reigns as Med Students Reveal Residency Fates.
PMID- 26434171
TI - Let's Measure It in Dollars and Cents.
PMID- 26434173
TI - Carey Medical College Graduates Second Class.
PMID- 26434174
TI - Gulfport Veterans' Hospital 1935-8.
PMID- 26434175
TI - Spotlight on: Physician Leadership Academy.
PMID- 26434176
TI - Physicians mean business. Physicians create jobs everywhere they go.
PMID- 26434178
TI - Uncertain future for school nurses.
PMID- 26434177
TI - "Trusts and universities need more cooperation".
PMID- 26434180
TI - NICE guidelines on treatment of diabetic ulcers.
PMID- 26434179
TI - Education inadequate for future care needs, warn nurse directors.
PMID- 26434181
TI - Meningitis vaccine should be followed up with paracetamol.
PMID- 26434182
TI - Important role of nursing needs more recognition, says crash nurse.
PMID- 26434183
TI - Open visiting leads to drop in complaints.
PMID- 26434184
TI - Community hospital research will look at nurse staffing levels.
PMID- 26434186
TI - "We must all be confident using evidence to shape our practice".
PMID- 26434185
TI - "Nurses are key to ensuring all patients are discharged safely".
PMID- 26434187
TI - Using hospital at home to reduce admissions.
AB - In the UK at present there is a constant pressure for inpatient beds; with this
comes a need to develop services so that patients can be managed in their own
homes. Although community nursing has historically been synonymous with district
nursing, with the ageing population and the need to manage the increasing numbers
of patients who have long-term conditions, community nursing is changing. This
article describes a hospital in the home service, developed by one NHS trust; it
not only delivers care traditionally provided in hospitals, but is also an
effective setting for student nurses to undertake practice placements.
PMID- 26434188
TI - Vital signs monitoring in hospitals at night.
AB - Vital signs are important indicators of patients' clinical condition and inform
required interventions. This article reports on a review of the literature on
current practice, which showed that nurses' compliance with monitoring protocols
is poor, particularly at night. This has important implications for patient
safety and outcomes.
PMID- 26434189
TI - Assessing the pulse rate in adult patients.
AB - Assessing the pulse is a common procedure and an important aspect of many nursing
interventions; it should always be done with care and reassessed as needed.
Assessment should always be taken seriously, with any deviations from the norm
reported to a senior clinician, and pulse rate, rhythm and strength must always
be documented. Pulses indicate numerous patient characteristics including the
degree of relaxation, regularity of cardiac contractions and sufficiency of
cardiac output. This article considers the relevant anatomy, physiology and
practice of pulse assessment and recording.
PMID- 26434191
TI - 60 seconds with Sam Foster.
PMID- 26434190
TI - Setting standards for high-quality placements.
AB - As part of a project undertaken by a local education and training board, a wide
range of stakeholders across South London were asked what makes a high-quality
practice placement for student nurses, and how that quality could be effectively
measured. This article outlines the drafting and testing of a set of quality
standards in a mix of provider settings. Although further refinement is required,
the standards enabled placement sites to question themselves about their own
education and training processes, strengthened their partnership with the
training and education board and facilitated the assurance that student nurses
receive safe, effective and compassionate preparation when they are on placement.
PMID- 26434192
TI - The hand that feeds.
PMID- 26434193
TI - [Help! Accumulation of manuscripts!].
PMID- 26434194
TI - [TERIFLUNOMIDE: A NEW ORAL IMMUNOMODULATING AGENT FOR MULTIPLE SCLEROSIS].
AB - Multiple sclerosis (MS) is the autoimmune, demyelinating, neurodegenerative
disorder of the central nervous system (CNS). There are nine drugs available in
Hungary reimbursed by the National Health Insurance Fund of Hungary (OEP) to
reduce the activity of the disease, from which seven can be used as first line
therapies. We have approximately 20 years of experience with the interferon beta
1a/1b and glatiramer-acetate products. Though in case of approximately 30% of the
patients using one of the first line drugs, the disease remains active, that we
call break-through disease. The reasons for breakthrough disease could be the
insufficient adherence and compliance, the appearance of neutralizing antibodies
or the high activity of the disease. One of the oral immunomodulating drugs for
MS, teriflunomide, was registered in Europe in 2013. Because of the anti
proliferative and anti-inflammatory effect of teriflunomide, it can be used for
the reduction of the disease activity in the relapsing-remitting course of MS.
The effect of teriflunomide was proved in one Phase II. and four Phase III.
(TEMSO, TOWER, TENERE, TOPIC) studies. Teriflunomide 14 mg once daily was able to
demonstrate in two consecutive placebo-controlled phase 3 clinical trials that
significantly reduces the relapse rate (31.5% and 36.3%) and in both studies
significantly reduces the sustained disability progression (29.8% and 31.5%)
moreover delays the appearance of the clinically definitive MS in patients with
clinically isolated syndrome (CIS). According to the TENERE study there were no
significant differences observed between teriflunomide 14 mg and IFNbeta-alpha a
s.c. in time to failure and annualized relapse rate but the treatment
satisfaction domains of global satisfaction, side-effects and convenience were
significantly improved with teriflunomide compared with s.c. IFNbeta-alpha.
PMID- 26434195
TI - [CONVULSIVE EFFECTS OF ANTIEPILEPTIC AGENTS].
AB - Antiepileptic drugs can provoke and worsen seizures, what is called paradoxical
effect. Paradoxical seizure worsening can occur as a nonspecific manifestation of
drug intoxication in number of antiepileptic drugs. The other type is a specific
type, when antiepileptic drugs with pure GABAergic and sodium channel blocker
mechanism of action provoke myoclonic, absence and atonic seizures in specific
epilepsy syndromes, mainly in idiopathic generalized epilepsies. Antiepileptic
drug-induced exacerbation of seizures is a common, often unrecognized clinical
problem, which can be avoided by a careful syndromic diagnosis and by using broad
spectrum antiepileptic drugs.
PMID- 26434196
TI - [DRUG THERAPY OF NEUROPATHIC PAIN BASED ON THE LATEST RECOMMENDATIONS].
AB - Neuropathic pain is considered as a special type of different pain conditions.
It's pathophysiological basis and treatment is completely different from the
nociceptive pain. The first comprehensive therapeutic guidelines published
approximately a decade ago recommended tricyclic antidepressants, anticonvulsants
and opioids. The recent summary presents and evaluates national and international
guidelines issued in the last five years. The most frequently suggested drugs by
all guidelines are amitriptyline, duloxetine, gabapentin and pregabalin.
Pregabalin is the only drug that is recommended first line in all guidelines
referred. Opioids are in the second or third line. There seems to be no major
development in the pharmacological treatment of the neuropathic pain compared to
the earlier recommendations. High quality studies of head to head comparisons and
effectiveness of combination therapy are still lacking.
PMID- 26434197
TI - DO PREVIOUS OFFENCES PREDICT VIOLENT ACTS IN PSYCHIATRIC PATIENTS? A
RETROSPECTIVE STUDY IN HUNGARY.
AB - AIM: To investigate the presence of offences in the previous past history of
perpetrators of violent acts who have undergone forced medical treatment.
METHODS: The documentation of all patients released over a 10-year period from
the National Institute of Forensic Psychiatry (IMEI) was reviewed. A comparison
was drawn between patients who were convicted of any type of offense before the
violent act (patients with previous offences-PPO) and those who were not
(patients with no previous offences-PNO). RESULTS: Eighty-six (29%) and 208 (71%)
patients formed the PPO and PNO groups, respectively. Prior contact with
psychiatric services was significantly higher in the PPO group (p=0.038) and this
group was also more likely to offend under the influence of a psychoactive
substance (p<0.001). Exceptional brutality and other qualifying factors were more
frequent in the PNO group (p=0.019). CONCLUSION: As IMEI is the only forensic
institution in Hungary, the picture presented here reflects the situation in the
entire country. A recidivism rate of 29% is within the internationally published
range.
PMID- 26434198
TI - EFFECTS OF MATERNAL EPILEPSY AND ANTIEPILEPTIC THERAPY IN WOMEN DURING PREGNANCY.
AB - OBJECTIVE: The aim of this study was to analyse the effects of epilepsy and
antiepileptic drug (AED) treatment on pregnancy and the perinatal outcome,
retrospectively. METHODS: We examined the obstetric and fetal outcomes among
women with epilepsy (WWE), who were followed-up at the Department of Neurology,
and who delivered at the Department of Obstetrics and Gynaecology (n=91) between
31th December 2000 and 31th March 2014. Statistical comparisons of different
obstetric and fetal parameters on a sample of 91 WWE and 182 non-WWE were
assessed by the chi-square-test, the independent sample t-test. RESULTS: The rate
of major congenital malformations (MCMS) among the newborns of all AEDs exposed
mothers was 7.69%. There were three peaks of seizures: during the third
trimester, during delivery and in the puerperium. The prevalence of miscarriages,
post-term birth and the rate of caesarean section were significantly higher among
the WWE than among the non-WWE (p=0.001; p<0.001; p=0.02). Parameters of neonates
(birth weight, birth length, head-, and chest circumference) were significantly
different between the WWE group and the non-WWE group (p=0.003, p<0.001, p<0.001,
p<0.001) CONCLUSIONS: In contrast with recent publications, there were
significant differences in the parameters of neonates between the two groups. Our
results are in accordance with those of previous studies from the aspect of AED
related MCM, the elevated risk of miscarriages and pre-existing hypertension.
PMID- 26434199
TI - LACK OF ASSOCIATIONS BETWEEN CLU AND PICALM GENE POLYMORPHISMS AND ALZHEIMER'S
DISEASE IN A TURKISH POPULATION.
AB - BACKGROUND AND PURPOSE: To investigate the association between the rs11136000
single nucleotide polymorphism (SNP) of the clusterin (CLU) gene, the rs541458
and rs3851179 SNPs of the phosphatidylinositol-binding clathrin assembly protein
(PICALM) gene and Alzheimer's disease (AD) in a Turkish population, and to
determine whether there are any relationships between the CLU and the PICALM
genotypes and behavioral and psychological symptoms of dementia (BPSD) in the
Turkish population. METHODS: One-hundred and twelve AD patients and 106 controls
were included in this study. BPSD were evaluated by the Behavioral Pathology in
Alzheimer's Disease Rating Scale (BEHAVE-AD). SNPs in the CLU and the PICALM gene
were genotyped by Real-Time PCR. Genotype distributions were assessed for the
groups of patients and controls, for the patient groups with and without each
BPSD, and "No BPSD" and "BPSD". RESULTS: The CLU and the PICALM genotypes were
similar in the AD and control subjects, and the groups with and without each
BPSD. There were also no significant differences between the "No BPSD" and the
"BPSD" groups for the PICALM genotypes, but even without a statistical
significance, it is notable that none of the "No BPSD" patients had genotype
pattern CLU-rs11136000-TT, and the female subjects with genotype pattern CLU
rs11136000-TT had higher mean score of BEHAVE-AD. CONCLUSION: This study claims
that investigated SNPs are not genetic risk factors for AD in a Turkish
population. In addition, the rs541458 and rs3851179 of PICALM SNPs are not
related to development of BPSD, but the rs11136000 of CLU SNP might be related to
development of BPSD in AD female Turkish subpopulation.
PMID- 26434200
TI - [SHIFTING FUNCTION OF WORKING MEMORY IN PSYCHOTIC DISORDERS].
AB - BACKGROUND AND AIMS: Mental disorders with psychotic features are overlapping in
many ways and there are a growing number of comparative studies in the last
decades regarding this. Cognitive deficit is well underpinned in schizophrenia,
but fewer studies are conducted in this area including patients with bipolar
affective disorder. Therefore the aim of the present study was to investigate the
cognitive performance of these two patient groups and healthy controls. The
Wisconsin Card Sorting Task is a very sensitive measure of the shifting function.
Schizophrenic patients perform consistently poorer on this task than healthy
controls, while there are not much data about individuals with bipolar affective
disorder. METHODS: The Wisconsin Card Sorting Task and clinical symptom rating
scales were administered to 26 patients with schizophrenia, 24 with bipolar
affective disorder and 21 healthy controls. RESULTS: Significant differences were
found among the performance of the three groups using four different dimensions
of the Wisconsin Card Sorting Task. The schizophrenic group made more
perseverative errors and achieved less conceptual level responses and completed
fewer categories compared to healthy controls. Patients with schizophrenia were
able to complete fewer categories and had fewer conceptual level responses than
the bipolar group. No significant differences were observed between patients with
bipolar disorder and healthy controls. CONCLUSIONS: According to these results,
patients with schizophrenia and bipolar affective disorder showed no similarities
on the Wisconsin Card Sorting Task. Bipolar patients performed the task on the
same level as healthy individuals did. The two mental disorders influence
cognitive performance differently.
PMID- 26434201
TI - GENETIC POLYMORPHISMS OF HUMAN beta-DEFENSINS IN PATIENTS WITH MULTIPLE
SCLEROSIS.
AB - AIMS: Recent studies have started to elucidate the contribution of microbiome to
the pathogenesis of multiple sclerosis (MS). It is also supposed, that
neuropathological alterations might be associated with abnormal expression and
regulatory function of antimicrobial peptides (AMPs), including defensins. It is
in our interest to investigate the relevance of the single nucleotide
polymorphisms (SNPs) of the DEFB1 gene and the copy number polymorphism of the
DEFB4 genes in MS. METHODS: DEFBI polymorphisms: c.-20G > A (rsl 1362), DEFB1 c.
44C > G (rsI 800972), DEFB1 c.-52G>A (rsl 799946), and the DEFB4 gene copy number
were investigated in 250 MS patients The control patients comprised 232 age- and
gender-matched healthy blood donors. The occurrence of the human beta-defensin 2
peptide (hBD2) in the plasma of controls and patients-was determined by ELISA.
RESULTS: The DEFB1 c.-44C>G polymorphism the GG protective genotype was much less
frequent among patients than among the controls. A higher frequency of a lower
(<4) copy number of the DEFB4 gene was observed in the patients with MS as
compared with the controls (43% vs. 28%, respectively). The median levels of the
circulating hBD2 in the patients were 150.6 +/- 12.71 pg/ml vs. 262.1 +/- 23.82
pg/mI in the control group (p<0.0001). Our results suggest that beta-defensins
play role in the development of MS.
PMID- 26434202
TI - [MEASURING THE FUNCTIONAL IMPAIRMENT OF THE LUMBAR SPINE].
AB - BACKGROUND AND PURPOSE: The purpose of our study was to outline the Hungarian
validation process of the Oswestry Disability Index, the Quebec Back Pain
Disability Scale, the Roland-Morris Disability Questionnaire and the Core Outcome
Measurement Index, as well as to draw up recommendations regarding their future
applications. METHODS: The Hungarian versions were created after a cultural and
linguistic adaptation. Next to the above-mentioned questionnaires, the
questionnaire booklet used for validation also contained the WHOQoL-BREF general
quality of life questionnaire and a pain measuring Visual Analog Scale. The data
of low-back pain patients were registered twice in two weeks. We determined the
internal homogeneity (Cronbach alpha), reproducibility, standard error of
measurement and the minimal detectable change of the questionnaires. Patients
were assigned into different two subgroups (surgical / non-surgical, with/without
affection of nerve roots) and differences between the subgroups were examined
with the help of the questionnaires. We determined the physical subscale of the
WHOQoL-BREF and the correlation between the pain and the studied questionnaires.
RESULTS: The value of Cronbach alpha was between 0.85 and 0.95. All four
questionnaires showed significant differences (p<0.001) between the subgroups.
The correlation studies brought strong and significant results (p<0.001, r>0.5)
in every case. The values of reproducibility were between 0.93-0.92. The results
of standard measurement error: 4.8 (Oswestry), 5.2 (Quebec), 1.6 (Roland-Morris),
0.59 (Core Index). The minimal detectable change was 13; 14; 4, and 2 points,
respectively. CONCLUSION: The Hungarian versions of all four questionnaires are
valid. They can be applied with scientific certainty to measure low back pain
patients. From the studied questionnaires, we especially recommend the wide
raging application of the Oswestry Disability Index and the Core Outcome
Measurement Index based on their psychometric and application features.
PMID- 26434203
TI - [Position Statement of Hungarian Epilepsy League: The use of valproate
preparations for epilepsy in pregnancy and in women of childbearing age].
PMID- 26434204
TI - [Dr. Pal Fejerdy receives the Eotvos-Jozsef Award].
PMID- 26434205
TI - [Experience with the use of short dental implants in the literature].
AB - According to the literature short dental implants have often been used for the
replacement of teeth in the daily praxis. The implantation of short dental
implants raise a lot of questions. The autors's aim is to collect the most
important experiences of current literature on the mentioned theme to oral
implantologists. In the article 33 reviews and clinical studies have been
overviewed. The analysis of the different studies suggest that the use of short
implants--taking into account of indications and contraindications--decreases the
incidence of complications and the patient's discomfort as well as the cost of
treatment. The use of short dental implants is proposed as an alternative method
in the daily dental praxis.
PMID- 26434206
TI - [Report form the symposium in honor of Professor Bob ten Cate -- Amsterdam, April
17, 2015].
PMID- 26434207
TI - [Surgery on virtual model and 3-dimensional printing of a surgical wafer for the
correction of a severe mandibular asymmetry].
AB - Correction of a severe facial asymmetry presents a challenge due to the geometric
complexity of the dentition, the bony structures and the soft tissues. In most
asymmetric cases two-jaw surgery is recommended. Manual model surgery is an
essential part of treatment planning but it can be complicated, time-consuming
and may contain potential errors. We present a case of a 26-year-old male with a
severe right-sided hemimandibular elongation when computerized simulation surgery
was performed instead of manual model surgery. High-resolution computer
tomography scan was done following presurgical orthodontics and the stack images
were reformatted into a three-dimensional structure. The symmetry of the maxilla
was corrected via a virtual Le Fort I osteotomy with the help of a three
dimensional planning software. A virtual intermediate surgical wafer was designed
and fabricated with a three-dimensional printer. Virtual bilateral sagittal split
osteotomy was performed and the mandible was rotated into the correct position to
visualize the movements of the osteotomized segments. Real surgery was
accomplished according to the virtual plan. The splint fitted well. There is a
significant improvement in the facial symmetry; the occlusion is good and stable.
This case supports the usage of computer-aided surgical planning and three
dimensional rapid prototyping for the correction of facial asymmetries.
PMID- 26434208
TI - [Difficulties in differential diagnosis of dentin dysplasia. Case report].
AB - In cases of periapical lesions of unknown origin we have to keep in mind the
possibility of dentin dysplasia. From the differential diagnostic point of view
of differential diagnosis it is important to recognize this disease as it
significantly influences the treatment modality. It is an anomaly of unknown
etiology that could affect both deciduous and permanent dentition. Dentin
dysplasia presentation varies clinically and radiologically. A rare manifestation
which affects 1: 100000 patients is spontaneously occurring either as periapical
abscess or odontogenic cyst. The affected teeth could become mobile and
eventually lost. Dentin dysplasia is a genetic disease which shows autosomal
dominant inheritance and characterized by abnormal formation of dentin structure
which occurs during tooth development. For this article we have reviewed
available literature and PubMed database. Dentin dysplasia increases the risk of
early tooth loss and associated with it esthetic and functional disturbances. As
a result it can influence the psychological and social status of the patients and
affect their quality of life.
PMID- 26434209
TI - [Dental management of hemorrhage-prone patients].
AB - The authors present a proposal of dental treatment and management of
anticoagulated patients and of patients on antiplatelet therapy, with the
approval by the Hungarian Association of Oral and Maxillofacial Surgeons and by
the Dental Implantology Association of Hungarian Dentists. This current guide was
based on recent Hungarian and on several foreign national guidelines and
considers significant publications from international literature.
PMID- 26434210
TI - [Dental and oral surgical treatment of a B haemophilic patient with high
inhibitor level. Case report].
AB - More than 1000 hemophilic male patients are registered in Hungary, from which
only a trace number suffers from factor IX inhibitory hemophilia. For correct
dental and oral surgical treatment of these patients mandatory cooperation is
required among medical specialties, exerting multi-staged haemostatic principles.
Authors represent in this case report the dental and oral surgical treatment of a
B hemophilic patient with high inhibitor level and describe possible local
haemostatic measures.
PMID- 26434211
TI - [Dr. Ferenc Konrad lived 70 years and few more days].
PMID- 26434213
TI - [80 years of dentistry education at Debrecen University, Hungary].
PMID- 26434212
TI - [In memory of Professor Dezso Kovacs].
PMID- 26434214
TI - Nurse entrepreneur recognized.
PMID- 26434215
TI - Retirement is a dream at 55, but not a reality. Can nurses work until 70?
PMID- 26434216
TI - Workforce shortages and retention of older nurses.
PMID- 26434217
TI - AUSTRALIA'S HEALTH CUTS. PAYING THE PRICE FOR AUSTERITY MEASURES.
PMID- 26434218
TI - Poor communication leads to poor outcomes.
PMID- 26434219
TI - Ageing with HIV.
PMID- 26434220
TI - Engaging with people with dementia in subacute care.
PMID- 26434221
TI - Challenges in self-care in older adults with diabetes.
PMID- 26434222
TI - Malnutrition and depression in older adults: Are these health issues too hard to
tackle?
PMID- 26434223
TI - A partnership approach to evaluating evidence-based practice project in aged
care.
PMID- 26434224
TI - Passion--the DNA that binds nursing.
PMID- 26434225
TI - The deteriorating diabetic client in residential aged care facilities.
PMID- 26434226
TI - Alcohol and drug screening for older Australians.
PMID- 26434227
TI - What do you do well? Positive questions improve life for older people living in
residential care.
PMID- 26434228
TI - Developing a conceptual understanding of 'quality continence care'.
PMID- 26434229
TI - Rapid Access Service.
PMID- 26434230
TI - Aged mental health--innovation in developing a specialist workforce.
PMID- 26434231
TI - Change of attitude to males involvement in childbirth.
PMID- 26434232
TI - Can feeling good strengthen relationships?
PMID- 26434233
TI - Annie.
PMID- 26434234
TI - Retention Mechanism for Ion-Pair Chromatography with Chaotropic Reagents. From
Ion-Pair Chromatography toward a Unified Salt Chromatography.
AB - The breakthrough of chaotropic mobile phase modifiers in reversed-phase high
performance liquid chromatography (RP-HPLC) is due to their strong potential to
provide adequate retention of ionic analytes without the blamed semipermanent
modification of the chromatographic packing often connected to the use of
classical ion-pair reagents. The lack of a physicochemical framework that is able
to unify eclectic experimental evidence concerning the use of a wide gamut of
ionic additives in RP-HPLC is the primary motive force for recent theoretical
efforts to model their behavior. The time-honored solvophobic theory cannot
properly explain salt effects. Its theoretical basis was recently questioned by
breaking experimental evidence at variance with the textbook knowledge of ionic
solutions interfaces; meanwhile, a recently proved extended thermodynamic
approach to ion-pair chromatography (IPC) is challenged by the breakthrough of
neoteric ionic additives whose behavior questions the rigidity of previous
retention schemes and bridges salting chromatographic phenomena to IPC. Building
on these research needs, the aims of this review are (1) to illustrate a
comprehensive theory of analyte retention in the presence of any kind of
electrolytes (hydrophobic ions, chaotropes, kosmotropes, ionic liquids [ILs]) to
capture and rationalize the main salting effects and to support their strong
practical impact for the separation of organic and inorganic ions, ionogenic,
neutral, and zwitterionic analytes; (2) to explain why ion-specific salting
chromatographic effects that represent a diachronic scientific consideration were
not satisfactorily explained in the rubric of the solvophobic theory; and (3) to
highlight the eligibility of chromatography as a basic technique that is able to
clarify the currently hotly debated behavior of ions at water interfaces. The
practical impact of chaotropic chromatography will also be detailed, and urgent
research needs and suggestions will be illustrated.
PMID- 26434235
TI - Mechanistic Aspects of Chiral Recognition on Protein-Based Stationary Phases.
PMID- 26434236
TI - Mechanistic Aspects and Applications of Chiral Ligand-Exchange Chromatography.
PMID- 26434237
TI - Glycosylation Analysis of Proteins, Proteoglycans, and Glycolipids Using
Capillary Electrophoresis and Mass Spectrometry.
PMID- 26434238
TI - Oligonucleotide Adducts as Biomarkers for DNA Damages. Analysis by Mass
Spectrometry Coupled to Separation Methods.
PMID- 26434239
TI - Quantitative in Silico Analysis of the Specificity of Graphitized (Graphitic)
Carbons.
PMID- 26434240
TI - Application of Column-Switching Methods in HPLC for Evaluating Pharmacokinetic
Parameters.
PMID- 26434241
TI - Chromatographic Procedures in a Regulated Environment.
PMID- 26434242
TI - The Use of Novel Materials as Solid-Phase Extractors for Chromatographic
Analysis.
PMID- 26434243
TI - Thin-Layer and High-Performance Thin-Layer Chromatographic Analysis of Biological
Samples.
PMID- 26434244
TI - Development of the Model for Local Drowning Surveillance System in Northeastern
Thailand.
AB - BACKGROUND AND OBJECTIVE: There is growing evidence that the drowning fatality
rate in Thailand has been increasing, particularly among children. The use of
public health surveillance system in accident injury, specifically from drowning,
at a community level is limited. This study aimed to develop a surveillance
system to reduce risk of drowning in a rural area of Thailand. MATERIAL AND
METHOD: A 7-step process was used to develop a model for local drowning
surveillance system based on community participation. The target population
consisted of 182 informants, 562 participating surveillance networks, and 21,234
villagers in two sub-districts of Ubon Ratchathani Province, northeastern
Thailand. Two similar sub-districts were chosen as comparison areas. RESULTS:
Fifteen months after implementation of the model for local drowning surveillance
system (MLDSS) was introduced, improvements were found in all identified risk
factors, and the incidence rate ratio of injury in the comparison areas was 23.36
times higher than in the target areas. CONCLUSION: In the developing world where
community bonds remain strong, governments need to encourage local officials, the
private sector and the wider community to work together in solving the problem of
drowning in their local areas. Such schemes will require national promotion and
basic funding.
PMID- 26434245
TI - Developing a Substance Literacy Scale for Thai Population.
AB - OBJECTIVE: To develop a substance literacy scale for Thai population. MATERIAL
AND METHOD: The research design was divided into 8 steps as follows: 1) devising
the items, 2) exploring construct validity of each factor 3) validating
reliability of each factor, 4) generating construct validity of scale, 5) testing
conceptual construct ofthe scale, 6) constructing alternated rating scales, 7)
conducting cognitive test, and 8) conducting pilot test. There were 15 experts
involved in the content validation of scale. The research was conducted with
3,824 samples of Thai population aged between 12-65 years old from all over the
country using the Stratified Three Stages Cluster sampling technique. RESULTS:
Two substance literacy scales were developed. A standard has questionnaire of 37
items. The scale content validity index was 0.65, concurrent validity was 0.648.
A short has questionnaire of 32 items. The scale content validity index was 0.86,
concurrent validity was 0.667. CONCLUSION: Both scales are simple and easy to
use. Scale characteristics are appropriate to assess the substance literacy of
population. It can be beneficial to planners for strategic development to respond
to the problem more accurately.
PMID- 26434246
TI - Size Estimation of Injecting Drug Users through the Network Scale-Up Method in
Thailand.
AB - BACKGROUND AND OBJECTIVE: Hard to reach populations such as injecting drug users
(IDU) is one, among the most at risk, for HIV infection in Thailand. This study
examined an indirect methodfor estimating the size of IDU population in Thailand.
MATERIAL AND METHOD: A household survey was conducted among 3,790 individuals who
were 12-65 years old, stayed at least 3 months in the sample households. Through,
reference groups and summation procedure, personal network size was estimated.
The participants were asked to identify the number of their acquaintances whom
they perceived to be IDU. Using the survey results with the network scale-up
method, the IDU population size was estimated. RESULTS: The personal network size
was estimated to be 71,000 ID Us. The estimated prevalence of total population in
Thailand was 110 IDUs in 100,000 population. CONCLUSION: Estimating population
sizes through the network scale-up method appeared to be an effective method in
terms of time, simplicity, and low cost as compared with more-conventional
methods.
PMID- 26434247
TI - Using Population Based Data on Drugs Abuse to Estimate the Relative Need for
Medical Services in Thailand.
AB - BACKGROUND AND OBJECTIVE: Epidemiological background shows a trend in drug abuse
and essential need for revising its strategic plans, allocating resources, and
advocating services for populations. The relative need for drug abuse prevention
and medical services across different geographic areas of Thailand, which has
been examined through an analysis of existing population-based datasets and
reported routinely. The objective was to develop an indicator of relative need
for drug abuse prevention and medical services. MATERIAL AND METHOD: Qualitative
data were collected as primary data sources from 10 focus group discussions
throughout Thailand. The primary data were integrated into study framework with
the result from literature review. Data sets in 2011 were retrieved from the
national databank to obtain variables regarding drug abuse. Multiple regression
and factor analysis were undertaken using the district as the unit of analysis.
RESULTS: A factor analysis, which revealed six factors that explained 64% of the
variance in the data set. Factors identified in the analysis were taken as
indicators of variation in the need for services as all of the drugs-related
variables loaded strongly on these factors. The distribution of ranks for factor
scores (determined through regression) obtained for these factors across
districts in Thailand showed that scores were highest in urban and suburban
areas. CONCLUSION: In terms of practical implications, the study results could be
used for resource allocation in medical service plans for community drug abuse.
PMID- 26434248
TI - The Prevalence and Associated Factors of Alcohol Consumption: A Cross-Sectional
Study in Khon Kaen, Thailand.
AB - BACKGROUND AND OBJECTIVE: Knowledge of the situation and risk factors associated
with alcohol consumption are essential for prevention and control measures of
health consequences. This study aims to explore the prevalence of alcohol
consumption and the factors associated with alcohol consumption in the population
aged 12-65 years. MATERIAL AND METHOD: This was a descriptive study. This survey
used multi-stage sampling and face-to-face interviews, carried out in both urban
and rural areas. Those interviewed were a representative sample of 876 people in
the ratio ofone male and one female to represent the household. Data were
collected by interviewers between 1 January and 28 February 2012. The data were
analyzed by frequency, percentage, mean, standard deviation, Chi-square, multiple
logistic regression, OR and 95% CI of OR. This study was approved by the ethics
and research institutional review board of Khon Kaen University No. HE53121.
RESULTS: The mean age of the respondents was 41.7 years (SD 13.6). The majority
of the respondents were the head of the family (33.9%), those educated to primary
school level (44.6%), living in rural areas (55.9%), who were married (70.7%),
and who were farmers (35.3%). The prevalence of alcohol consumption during the
previous week was 6.3% (95% CI: 4.7 to 7.9), during the previous month was 35.2%
(95% CI: 32.0 to 38.3), and during the previous year was 41.0% (95% CI: 37.7 to
44.2). The factors associated with alcohol consumption were gender (male/female)
AOR 6.5 (95% CI 4.4 to 8.9, p-value < 0.001) age group (25-44/45-65) AOR 1.6 (95%
CI 1.1 to 2.4, p-value = 0.011) location (rural/urban) AOR 1.7 (95% C1 1.3 to
2.4, p-value < 0.001) educational attainment (bachelor or master degree/primary
school) AOR 1.7 (95% CI 1.1 to 2.8, p-value = 0.031) and the occupation (laborer)
AOR 1.6 (95% CI 1.1 to 2.4, p-value = 0.015). CONCLUSION: Knowing the prevalence
and factors associated with alcohol consumption are essential to understanding
the situation, solving related problems and using the information in the campaign
for the prevention and control of alcohol consumption
PMID- 26434249
TI - Effect of Andrographis paniculata Extract on Triglyceride Levels of the Patients
with Hypertriglyceridemia: A Randomized Controlled Trial.
AB - BACKGROUND: Hypertriglyceridemia is one of the risk factors for cardiovascular
disease, and reduction oftriglyceride (TG) level is recommended in clinical
practice guidelines for the treatment. Recently, andrographolide, a main active
compound of Andrographispaniculata has been shown to possess hypolipidemic
effects in animals. OBJECTIVE: To investigate the TG-lowering effects of A.
paniculata extract (APE) in patients with hypertriglyceridemia (TG >= 150 mg/dL)
using gemfibrozil treatment as the reference. MATERIAL AND METHOD: A randomized
controlled clinical trial was carried out in sixty subjects with
hypertriglyceridemia. They were divided into three groups and treated with low
dose of APE (APE-L, andrographolide 71.64-72.36 mg/day), high dose of APE (APE-H,
andrographolide 119.64-120.36 mg/day), and gemfibrozil 300 mg/day. The treatments
were conducted for 8 weeks. Guidance on lifestyle modifications was provided.
RESULTS: The primary endpoint was the mean difference +/- SD (95% CI) in TG
levels (baseline from the end of treatment), which were -3 +/- 125.6 (-59.1,
58.5), 41.6 +/- 86.3 (1.2, 82), and 57.1 +/- 94.9 (12.7, 101.6) in the APE-L, APE
H, and gemfibrozil groups, respectively. APE-H 120 mg/day and gemfibrozil 300
mg/day caused a significant reduction of TG level (P = 0.0442 and 0.0145,
respectively) when compared to the baseline. There was no notable difference in
the safety or tolerability among the treatment groups. CONCLUSION: In patients
with modest hypertriglyceridemia with lifestyle intervention, APE-H reduced the
TG level comparable to the effect of gemfibrozil 300 mg/day. APE treatment was as
tolerable as gemfibrozil treatment. Hence, Andrographis paniculata might be used
as an alternative medicine in treating hypertriglyceridemic patients.
PMID- 26434250
TI - The Development of a Readiness Scale for Changing Farmers' Behaviors of Using
Pesticides.
AB - BACKGROUND AND OBJECTIVE: Inappropriate pesticide-using behaviors impose
significant negative impacts on health and environment. Developmentalprograms to
change such behaviors offarmers should target those who are ready to change in
order to achieve efficiency. The objective was to develop a readiness scale in
changing behavior ofusing pesticides offarmers. The scale of this study is
expected to be used in recruiting targetfarmers in developmental programs.
MATERIAL AND METHOD: A cross-sectional study was divided into two phases. The
first phase, qualitative method, performed on 17farmers participated to seek
factors related to the farmers' safe use of pesticides. The second phase,
quantitative method to develop the readiness scale, an exploratoryfactor analysis
(EFA) was analyzed on 230farmers and was randomly selected to measure the scale's
construct validity, internal consistency (reliability), one-dimensionality and
the appropriate cut-off point, respectively. RESULTS: Farmers' pesticide use,
safety behaviors involved several factors, and are applied to create a set
ofquestions on the readiness scale; there were 33 main items (with 40 sub-items),
which could be grouped into 8 factors associated with farmers using pesticide
safety, the scale, the best way to predict farmers who are ready to change.
Finally, they were reduced to 23 main questions with 30 sub-questions in the
scale. CONCLUSION: The development of a readiness scale application of changing
behaviors as a guide, to assess content validity using index of item-objective
congruence measurement (IOC), the exploratory factor analysis was used to
determine an item and to test reliability on the scale. The scale can be a useful
tool for recruiting farmers into intervention program in changing pesticide use,
safety behaviors.
PMID- 26434251
TI - Disability-Adjusted Life Years among Drug Users in Khon Kaen: An Evidence-Based
Approach.
AB - OBJECTIVE: To examine the Disability Adjusted Life Years (DALYs) among drug users
in Khon Kaen. MATERIAL AND METHOD: A cross-sectional descriptive study was
conducted between January 2014 and February 2015. Patients' medical records,
supported by the Khon Kaen Provincial Public Health Office, were used for data
regarding the treatment ofthe drug users between October 2013 and September 2014.
SPSS version 19.0 for windows was used to analyze descriptive statistics and
Pearson's correlations. RESULTS: A review of medical records revealed a total
number of drug users were 3,605 males (92.25%) and 303 females (7.75%). A total
of 2,195 cases (56.17%) were drug dependence. 20 drug users died due to drug
related causes. A total DALYs were 6,772.26 and a prevalence rate of DALYs was
3.76/1,000 populations. The correlation analyses showed significantly factors
related to the DALYs among drug users were age, occupation, pattern of drug use,
levels of severity, drug-related death and treatment services. CONCLUSION: The
DALYs were apparently high among male drug users, who completed primay school
education, were drug-dependent and being treated in group therapy. The health
authorities may use these associated factors in order to develop or improve
programs related to prevention, harm reduction and treatment services
effectively.
PMID- 26434252
TI - Effectiveness of Culturally Appropriate Initiative on Drug-Related Harm Reduction
for Sex Workers on the Thai/Malaysian Border.
AB - BACKGROUND AND OBJECTIVE: Drug use can harm to sex workers. Abstinence
intervention, however, may not be appropriate since drug use fosters their career
performance. The objective was to develop the culturally appropriate model for
sex workers participation on drug demand reduction at the Thailand/Malaysian
border MATERIAL AND METHOD: This study was a pre-post quasi-experimental design.
Tripartite participation was used to develop the model aiming to reduce harm
regarding drug use. The study carried out during June 2010-May 2011. Data were
collected from 150 key informant interviews, 56 focus group discussions, 22
participant observations in various situations, and numerous related materials.
Descriptive statistics, survival analysis and 95% confidence interval were
utilizedfor quantitative data. Qualitative data were analyzed by content
analysis. RESULTS: Drug related harm reduction was evaluated at two-week time
along implementation period of 12 months. 89.5% of all sessions introduced could
decrease drug related harm. Of all sex workers participated in the study,
intended to treat analysis showed 86.9% success rate (95% CI; 77.1, 96.7). Of
these, 32.6% became abstinence, 39.1% reduced most of drug related harm. 13.0%
reduced partial drug related harm either lessfrequency, less quantity, less
concentration, decrease types of drugs/switch to safe drugs or safer method of
administration. 2.2% was infancy stage, which needed further support. CONCLUSION:
Key success ofthe model was tripartite participation. With active leaders and
strong support, sex workers were continually motivated to reduce harm regarding
drug use.
PMID- 26434253
TI - Prevalence and Factors Associated with the Utilization of Dental Care Services
among Factory Workers in Nava Nakorn Industrial Estate, Pathumthani Province,
Thailand.
AB - OBJECTIVE: The present study aimed to find out the utilization prevalence of
dental care services among factory workers over a period of one year and factors
associated with utilization of dental care services. MATERIAL AND METHOD: This
was a cross-sectional analytic study. The study population was factory workers in
Nava Nakorn Industrial Estate randomly sampled using Probability Proportion to
Size Cluster Sampling Method. The tool was a questionnaire about utilization of
dental care services. RESULTS: Among the sample group of 1,500 workers from 16
factories, almost 2/3 (63.9%) had never used any dental care services in the
previous year while only 36.1% did. A multivariable logistic regression analysis
showed that workplace, accommodation, tooth decay, toothache history,
transportation, experience in using social security fund for dental care
services, availability and accessibility of dental care services, brushing teeth
regularly after meals, using dental care services regularly in a dental clinic,
and agreement with the idea that a tooth extraction and medication by a dentist
could reduce the risk of progression of disease, statistical significance (p
value < 0.05), were factors associated with the utilization of dental care
services at R2 (The Nagelkerke R Square) 0.38. CONCLUSION: That the prevalence of
the factory workers who did not use dental care services during the last one year
was 63.9 percent. This study identified three groups of factors associated with
the utilization of dental care services as: 1) Predisposing factors, 2) Enabling
factors, and 3) Need factors.
PMID- 26434254
TI - A Fluorescence Polarization Assay To Detect Steroid Hormone Traces in Milk.
AB - Steroids are a class of hormones improperly used in livestock as growth-promoting
agents. Due to their high risk for human health, the European Union (EU) has
strictly forbidden the administration of all natural and synthetic steroid
hormones to food-producing animals, and the development of new rapid detection
methods are greatly encouraged. This work reports a novel fluorescence
polarization assay, ready to use, capable of detecting 17beta-estradiol directly
in milk samples with a low limit of detection of <10 pmol. It is based on the
coupling of monospecific antibodies against 17beta-estradiol and fluorophores,
capable of modulating the fluorescence polarization emission on the basis of the
specific binding of antibodies to fluorescence-labeled 17beta-estradiol
derivative. The successful detection of 17beta-estradiol has disclosed the
development of an efficient method, easily extensible to any food matrix and
having the potential to become a milestone in food quality and safety.
PMID- 26434255
TI - SELF-REPORTED MORBIDITY AND BURDEN OF DISEASE IN UTTAR PRADESH, INDIA: EVIDENCE
FROM A NATIONAL SAMPLE SURVEY AND THE MILLION DEATHS STUDY.
AB - Uttar Pradesh is India's most populous state with a population of 200 million.
Any change in its fertility and mortality is bound to bring change at the
national level. This study analysed the burden of disease in the state by
calculating the disability-adjusted life year (DALY) for infectious and non
communicable diseases. Data were from two rounds (52nd and 60th) of the National
Sample Survey Organization (NSSO) survey conducted in 1995-96 and 2004,
respectively, and the Million Deaths Study (MDS) of 2001-03. Descriptive and
multivariate analyses were carried out to identify the determinants of different
types of self-reported morbidity and DALY. The results show that in Uttar Pradesh
the prevalence of all selected self-reported infectious and non-communicable
diseases increased over the study period from 1995 to 2004, and in most cases by
more than two times. The highest observed increase in prevalence was in non
communicable diseases excluding CVDs, which increased from 7% in 1995 to 19% in
2004. The prevalence was higher for those aged 60 and above, females, those who
were illiterate and rich across the time period and for all selected morbidities.
The results were significant at p<0.001. The estimation of the DALY revealed that
the burden of infectious diseases was higher during infancy, noticeably among
males than females in 2002. However, females aged 1-5 years were more likely to
report infectious diseases than corresponding males. The age distribution of the
DALY indicated that individuals aged below 5 years and above 60 years were more
susceptible to ill health. The growing incidence of non-communicable diseases,
especially among the older generation, puts an additional burden on the health
system in the state. Uttar Pradesh has to grapple with the unresolved problem of
preventable infectious diseases on the one hand and the growth in non
communicable disease on the other.
PMID- 26434256
TI - Antioxidant activities of chestnut nut of Castanea sativa Mill. (cultivar
'Judia') as function of origin ecosystem.
AB - The antioxidant properties of different ecotypes of chestnut nut (cv. Judia) were
studied. Total phenolics and flavonoids were also determinated. Total phenolics
amount ranged from 9.6mg/g of GAE (hottest ecotype, Murca) to 19.4mg/g of GAE
(coldest ecotype, Valpacos). Gallic and ellagic acid were the predominant
compounds and Valpacos had the highest values while, Murca had the lowest ones.
The antioxidant capacity of ethanolic extracts were evaluated through several
biochemical essays: ABTS (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic
acid)) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging activity, FRAP
(ferric reducing/antioxidant power) and inhibition of oxidative haemolysis in
erythrocytes. In order to evaluate the antioxidant efficiency of each ecotype,
the EC50 values were calculated. Once again Valpacos revealed the best
antioxidant properties, presenting much lower EC50 values. Climatic conditions
influence seems to be a limiting factor for production of phenolic compounds and
consequently for the antioxidant properties of chestnut nuts.
PMID- 26434257
TI - Relevance of calpain and calpastatin activity for texture in super-chilled and
ice-stored Atlantic salmon (Salmo salar L.) fillets.
AB - The aim of the present experiment was to measure the protease activities in ice
stored and super-chilled Atlantic salmon (Salmo salar) fillets, and the effect on
texture. Pre-rigour fillets of Atlantic salmon were either super-chilled to a
core temperature of -1.5 degrees C or directly chilled on ice prior to 144h of
ice storage. A significantly higher calpain activity was detected in the super
chilled fillets at 6h post-treatment compared to the ice-stored fillets and
followed by a significant decrease below its initial level, while the calpastatin
activity was significantly lower for the super-chilled fillets at all time
points. The cathepsin B+L and B activities increased significantly with time post
treatment; however, no significant differences were observed at any time points
between the two treatments. For the ice stored fillets, the cathepsin L activity
decreased significantly from 6 to 24h post-treatment and thereafter increased
significantly to 144h post-treatment. There was also a significantly lower
cathepsin L activity in the super-chilled fillets at 0h post-treatment. No
significant difference in breaking force was detected; however, a significant
difference in maximum compression (Fmax) was detected at 24h post-treatment with
lower Fmax in the super-chilled fillets. This experiment showed that super
chilling had a significant effect on the protease activities and the ATP
degradation in salmon fillets. The observed difference in Fmax may be a result of
these observed differences, and may indicate a softening of the super-chilled
salmon muscle at 24h post-treatment.
PMID- 26434258
TI - Volatile compounds in low-acid fermented sausage "espetec" and sliced cooked pork
shoulder subjected to high pressure processing. A comparison of dynamic headspace
and solid-phase microextraction.
AB - Two extraction techniques, dynamic headspace extraction (DHE) and solid-phase
microextraction (SPME), were compared to assess the effect of high-pressure
treatment (400MPa, 10min, 12 degrees C) on the volatile compounds of low-acid
fermented sausage "espetec" and sliced cooked pork shoulder stored at 4 degrees
C. DHE was more efficient at extracting low-boiling compounds such as ethanal,
2,3-butanedione and alcohols, while SPME extracted more efficiently a higher
number of chemical families, especially fatty acids. The effect of pressurisation
on the volatile fraction of "espetec" was better categorized by DHE, whereas SPME
was more appropriate for cooked pork shoulder. The volatile fraction of "espetec"
changed slightly after pressurisation, mainly showing a decrease in the levels of
lipid-derived compounds, like linear alkanes, aldehydes, or 1-alcohols in
pressurised samples. The volatile profile of cooked pork shoulder underwent
substantial changes during refrigerated storage, mainly due to microbial
metabolism, most of these changes being limited by HPP.
PMID- 26434259
TI - Differential inhibition of human colon cancer cells by structurally similar
flavonoids of citrus.
AB - A number of studies in the recent years have evaluated the anti-proliferative
activity of flavonoids. Although certain studies investigated the structure
activity based on the phenotypic assays, no study has correlated the flavonoids
structure with the ability to alter gene/protein expression. Present study was
focused to understand the structure-function relationship of citrus flavonoids in
terms of their ability to alter the gene expression in the colon adenocarcinoma
cells. Eight structurally related flavonoids found in citrus were evaluated for
their ability to inhibit colon cancer (SW480) cells, as well as change the
expression of apoptosis related genes/proteins. Apigenin and quercetagetin
demonstrated most significant inhibition of cell proliferation with 63.6% and
45.7% inhibition of cell growth at 200MUM after 48h of incubation, respectively.
The cell death was also confirmed by images of fluorescently tagged cells.
Furthermore, up-regulation of Bax/Bcl2 protein ratio as well as activation of
Caspase3 at 200MUM at 48h confirmed the induction of apoptosis by apigenin and
quercetagetin. In addition, results suggest that the change in Bax/Bcl2 ratio by
apigenin and quercetagetin seems to be due to their ability to alter the
expression of bax and bcl2 transcription. Results of the currents study suggest
that among the citrus flavonoids, double bond between C2 and C3 and hydroxyl
group at C3, C6 are highly decisive for the proliferation inhibition and
apoptosis induction ability. Taken together, these results demonstrate that among
the major flavonoids of citrus, apigenin and quercetagetin have potent anti
cancer activity through inducing apoptosis in SW480 human colon cancer cells.
PMID- 26434260
TI - Co-occurrence of aflatoxins, ochratoxin A and zearalenone in barley from a
northern region of Spain.
AB - One-hundred and twenty-three barley samples from a region of Spain (Navarra) were
analysed in order to evaluate the possible co-occurrence of aflatoxins (AFB1,
AFG1, AFB2 and AFG2), ochratoxin A (OTA) and zearalenone (ZEA). The results
indicated that 80% of the samples presented detectable, although very low levels,
of two or more mycotoxins. The most frequent combinations were AFB1 and OTA;
AFB1, ZEA and OTA; and AFB1 and ZEA. In general, the statistical study did not
show significant differences between levels or incidence for the mycotoxins in
different years of harvest, variety of barley, farming or origin. The calculated
values for daily intake were low and the risk to consumers could be assumed to be
very low. However, the co-occurrence of several mycotoxins, and therefore
synergic or additive effects, should be taken into account when determining
permitted levels or risk assessment.
PMID- 26434261
TI - The mechanism underlying proliferation-inhibitory and apoptosis-inducing effects
of curcumin on papillary thyroid cancer cells.
AB - Recently, many studies on health benefits associated with curcumin have been
reported. In this study, the effects of curcumin on apoptosis of papillary
thyroid cancer cell line K1 and its potential mechanisms were investigated.
Curcumin was found to significantly inhibit cell viability and promoted cell
apoptosis in a dose-dependent manner. Moreover, curcumin-induced cell apoptosis
was characterized with a rapid stimulation of reactive oxygen species (ROS)
production. Furthermore, curcumin-induced ROS generation led to the loss of
mitochondrial membrane potential (MMP) and the disturbance of intracellular
Ca(2+) concentration. A decrease in expression of Bcl-2 and the cleavage of poly
ADP-ribose polymerase (PARP) were observed after exposure to curcumin. Results of
this study may elucidate the curcumin-induced apoptosis effects on K1 cells.
Thus, our results indicate a role of curcumin as health-promoting food
ingredient, as well as a potential chemotherapeutic agent which is able to fight
against papillary thyroid cancer.
PMID- 26434262
TI - Effect of temperature and air velocity on drying kinetics, antioxidant capacity,
total phenolic content, colour, texture and microstructure of apple (var. Granny
Smith) slices.
AB - The aim of this work was to study the effect of temperature and air velocity on
the drying kinetics and quality attributes of apple (var. Granny Smith) slices
during drying. Experiments were conducted at 40, 60 and 80 degrees C, as well as
at air velocities of 0.5, 1.0 and 1.5ms(-1). Effective moisture diffusivity
increased with temperature and air velocity, reaching a value of 15.30*10(
9)m(2)s(-1) at maximum temperature and air velocity under study. The rehydration
ratio changed with varying both air velocity and temperature indicating tissue
damage due to processing. The colour difference, DeltaE, showed the best results
at 80 degrees C. The DPPH-radical scavenging activity at 40 degrees C and 0.5ms(
1) showed the highest antioxidant activity, closest to that of the fresh sample.
Although DeltaE decreased with temperature, antioxidant activity barely varied
and even increased at high air velocities, revealing an antioxidant capacity of
the browning products. The total phenolics decreased with temperature, but at
high air velocity retardation of thermal degradation was observed. Firmness was
also determined and explained using glass transition concept and microstructure
analysis.
PMID- 26434263
TI - Preparation and properties of rutin-hydrolyzing enzyme from tartary buckwheat
seeds.
AB - A rutin hydrolyzing enzyme (RHE) was isolated from Fagopyrum tataricum Moench
seeds by using ammonium sulphate fractionation, anion exchange and size exclusion
chromatography. The purified RHE has an apparent molecular weight of about 70kDa
determined by SDS-PAGE, with an isoelectric point (pI) (determined by isoelectric
focusing) of 6.7. RHE has a specific catalytic activity toward rutin when
incubated together with rutin at 37 degrees C for 30min in the presence of 20%
ethanol, and its Km value for rutin is 1.04*10(-3)M. The RHE catalytic product
analyzed by HPLC displayed high similarity with quercetin and this is confirmed
by (1)H NMR spectroscopy and LC-ESI-MS/MS, suggesting that the RHE hydrolysis
product is quercetin. These results suggest that the RHE from tartary buckwheat
seeds is a specific rutin-hydrolyzing enzyme, providing a new enzymatic
preparation method for quercetin.
PMID- 26434264
TI - Nutritional and functional properties of Vicia faba protein isolates and related
fractions.
AB - The goal of this research was the characterisation of Vicia faba (broadbean)
protein isolates and related fractions in order to determine whether this grain
legume could be used for production of high quality protein products and other
fractions rich in functional components. Alkaline extraction of the defatted seed
flour, followed by precipitation at the isoelectric pH, yielded a 92% protein
isolate with a high oil absorption capacity. The contents of the favism-inducing
glycosides, vicine and convicine, in the isolate were reduced by more than 99% as
compared to the original flour, although the amino acid composition was similar
to that of the flour. Some of the by-products of protein isolate production may
also be of interest from a nutritional and functional point of view. Thus, the
oil resulting from hexane extraction of the flour is rich in unsaturated fatty
acids, and polyphenols (resulting from extraction of the defatted flour with
acetone) showed a high ABTS radical-scavenging activity. In addition, the solid
residue (resulting from protein solubilisation) was high in fibre and showed good
water absorption. These results show good nutritional and functional properties
in V. faba protein isolates and related fractions, which may favour the
revalorisation of this traditional bean crop.
PMID- 26434265
TI - Glycidyl esters in refined palm (Elaeis guineensis) oil and related fractions.
Part II: practical recommendations for effective mitigation.
AB - In a previous work, it was shown that at high temperatures (up to 280 degrees C)
glycidyl esters (GE) are formed from diacylglycerols (DAG) via elimination of
free fatty acid (FFA). In the present study, the impact of DAG content and
temperature on the formation of GE using a model vacuum system mimicking
industrial edible oil deodorization is investigated. These deodorization
experiments confirmed that the formation of GE from DAG is extensive at
temperatures above 230-240 degrees C, and therefore, this value should be
considered as an upper limit for refining operations. Furthermore, experimental
data suggest that the formation of GE accelerates in particular when the DAG
levels in refined oils exceed 3-4% of total lipids. Analysis of the lipid
composition of crude palm oil (CPO) samples allowed the estimation that this
critical DAG content corresponds to about 1.9-2.5% of FFA, which is the
conventional quality marker of CPO. Moreover, high levels (>100ppm) of GE were
also found in palm fatty acid distillate samples, which may indicate that the
level of GE in fully refined palm oils also depends on the elimination rate of GE
into the fatty acid distillate.
PMID- 26434266
TI - Effect of cooking method on carnosine and its homologues, pentosidine and
thiobarbituric acid-reactive substance contents in beef and turkey meat.
AB - Commercial samples of beef and turkey meat were prepared by commonly used cooking
methods with standard cooking times: (1) broiled at 200 degrees C for 10min, (2)
broiled at a medium temperature (140 degrees C) for 10min, (3) cooked by
microwave (MW) for 3min and then grilled (MW/grill) for 7min, (4) cooked in a
domestic microwave oven for 10min, and (5) boiled in water for 10min. The raw and
cooked meats were then analysed to determine the carnosine, anserine,
homocarnosine, pentosidine, and thiobarbituric acid-reactive substance (TBARS)
contents. It was observed that boiling beef caused a loss of approximately 50% of
the carnosine, probably because of the high water solubility of carnosine and its
homologues; cooking by microwave caused a medium loss of the anti-oxidants of
approximately 20%; cooking by MW/grill led to a reduction in carnosine of
approximately 10%. As far as the anserine and homocarnosine contents were
concerned, a greater loss was observed for the boiling method (approximately 70%)
while, for the other cooking methods, the value ranged from 30% to 70%. The data
oscillate more for the turkey meat: the minimum carnosine decrease was observed
in the cases of MW/grill and broiling at high temperature (25%). Analogously, the
anserine and homocarnosine contents decreased slightly in the case of MW/grill
and broiling at a high temperature (2-7%) and by 10-30% in the other cases. No
analysed meat sample showed any traces of pentosidine above the instrumental
determination limits. The cooked beef showed an increased TBARS value compared to
the raw meat, and the highest values were found when the beef was broiled at a
high temperature, cooked by microwave or boiled in water. The TBARS value of the
turkey meat decreased for all the cooking methods in comparison to the TBARS
value of the fresh meat.
PMID- 26434267
TI - Phenolic compounds in strawberry (Fragaria x ananassa Duch.) fruits: Composition
in 27 cultivars and changes during ripening.
AB - Phenolic compounds in fruits of 27 cultivars of strawberry (Fragaria x ananassa
Duch.) grown in Norway were characterised and quantified by HPLC-DAD-MS(n). Total
phenolic content, calculated as the sum of the individual compounds, varied 2.3
fold among cultivars, i.e., from 57 to 133mg/100g of fw. There were significant
differences among cultivars in concentration of all phenolic compounds. The
highest variation between cultivars was found for cinnamoyl glucose (0.6
24.9mg/100g of fw). Concentration of anthocyanins, the most abundant class of
phenolic compounds in the majority of the cultivars, varied from 8.5 to
65.9mg/100g of fw. Flavan-3-ols (11-45mg/100g of fw) and ellagitannins (7.7
18.2mg/100g of fw) contributed on average 28% and 14% to total phenolic contents
in the strawberry cultivars, respectively. In three cultivars harvested at three
stages of ripeness, anthocyanins and cinnamic acid conjugates were the compounds
most affected by ripening. The anthocyanin profile for the individual cultivars
was only slightly affected by ripening and growing conditions.
PMID- 26434268
TI - Influence of filtration on volatile compounds and sensory profile of virgin olive
oils.
AB - The influence of filtration through a hydrophilic cotton layer on volatile
compounds, sensory characteristics and colour of two monovarietal oils was
investigated in this study. Volatiles were evaluated using headspace solid-phase
microextraction-gas chromatography. After the filtration of Buza oils only a
slight increase in total alcohols was noticed. In filtered Crna oils a
significant decrease of total alcohols and slight changes in total aldehydes,
total ketones and total C5 volatile compounds concentration were detected. No
significant influence on the sensory scores of oils, but some slight changes in
sensorial profiles were noted (slightly higher intensities of sensory
characteristics apple and grass, and higher values of the lightness L(*) in
filtered samples). The results point to unequal filtration impact on different
monovarietal oils and could be useful in developing targeted technologies for
specific monovarietal oils quality improvement.
PMID- 26434269
TI - Antioxidant activity of protein hydrolysates derived from threadfin bream surimi
byproducts.
AB - Antioxidant activities of protein hydrolysates from threadfin bream surimi
wastes, including frame, bone and skin (FBS) and refiner discharge (RD), were
investigated. FBS and RD were rich in Lys, Glu, Gly, Pro, Asp, Leu, His, Tyr and
Phe. FBS was hydrolysed to a greater extent than RD regardless of proteinases
tested (Virgibacillus sp. SK33 proteinase, Alcalase, pepsin and trypsin). Pepsin
hydrolysed FBS, at a 5% degree of hydrolysis (DH), showed the highest antioxidant
activity based on 2,2'-azinobis (3-ethyl-benzothiazoline-6-sulphonate) (ABTS)
radical (0.455+/-0.054mg Trolox equivalents/mg leucine equivalents), ferric
reducing antioxidant power (FRAP) (0.221+/-0.005mM Trolox equivalents) and
inhibition of beta-carotene bleaching assays. FBS hydrolysates showed higher
antioxidant activity based on chemical assays than their RD counterparts.
However, FBS and RD hydrolysates protected HepG2 cells against tert-butyl
hydroperoxide-induced oxidative damage to a similar extent. Therefore, FBS and RD
hydrolysates have a potential as antioxidative neutraceutical ingredients.
PMID- 26434270
TI - Aroma potential of Brancellao grapes from different cluster positions.
AB - In this study the presence of aroma compounds in grapes of Brancellao (Vitis
vinifera L.) was investigated in order to obtain its aroma potential fingerprint.
It is well known that differences exist in aromatic compounds amongst grapevine
varieties at ripening stages. Within the framework of an increasingly competitive
market, the chance of obtaining different wines from vines of the same variety
grown at the same vineyard is becoming of increasing importance. This can be done
through the managing of the vineyard, but also some wineries have assayed the
separation of the tip and shoulder berries of the clusters of a specific variety
with this objective. In this work it is evaluated that, in the final stages of
maturation, differences exist in the probable alcoholic degree, total acidity of
the must, as well as in the aromatic composition of skin and flesh of berries
coming from the tips and shoulders of the clusters. Gas chromatography coupled to
mass spectrometry (GC-MS) was used to determine the aromatic composition, in the
skin and flesh of each sample, either tip or shoulder berries from the clusters.
The obtained results showed that there was not variability for the probable
alcoholic degree and total acidity between the shoulders and tips, whereas there
was variability for their aromatic composition. For the berries from the tips of
the clusters most of volatiles were found in the flesh (except aldehydes) and
spicy and floral nuances (with the only exception of beta-ionone) were in higher
proportions. For the berries from the shoulders of the clusters, most of
volatiles were found in the skin (monoterpenes, norisoprenoids, aldehydes, and C6
alcohols), where the flesh was slightly richer in aromatic alcohols, volatile
phenols and pantolactone; beta-ionone and herbaceous nuances were in higher
proportions. These results are promising for those wineries that are considering
the chance of separating berries from tips and shoulders of the clusters for the
elaboration of different quality wines.
PMID- 26434271
TI - Chemical composition and anti-proliferative and anti-inflammatory effects of the
leaf and whole-plant samples of diploid and tetraploid Gynostemma pentaphyllum
(Thunb.) Makino.
AB - Leaf and whole-plant samples of the diploid and tetraploid Gynostemma
pentaphyllum (GP) were investigated and compared for their chemical compositions,
and their potential anti-proliferative and anti-inflammatory effects. The highest
levels of total flavonoids and phenolics were observed in the diploid leaf
botanical (2L3) at 36.84mg rutin equiv/g and 41.15mg gallic acid equiv/g,
respectively. The diploid leaf sample (2L2) had the highest amount of rutin and
quercetin contents of 77.7MUmol quercetin equiv/g. The tetraploid whole-plant
botanical (4L3) had the highest total saponin content of 227.1mg gypenoside
equiv/g. Extracts from all tested GP samples showed time- and dose-dependent
antiproliferative effects in HT-29 cells, and the diploid leaf samples had the
overall highest inhibitory activity. These extracts had different order of
antiproliferative properties in the LNCaP cells, suggesting the potential
selective inhibition of GP extracts against different types of cancer cells and
the effect of the cell model in screening and evaluation of antiproliferative
components. In addition, the diploid leaf extracts showed the strongest
inhibitory effects on the expression of TNF-alpha, IL-6 and COX-2 mRNA at final
concentrations of 0.2 and 1mg botanical equiv/ml media. The results from this
study will be used to develop new nutraceutical products from G. pentaphyllum.
PMID- 26434272
TI - Possible causes of variation in acrylamide concentration in French fries prepared
in food service establishments: an observational study.
AB - Acrylamide is a probable human carcinogen, and its presence in a range of fried
and oven-cooked foods has raised considerable health concern world-wide. Dietary
intake studies observed significant variations in acrylamide concentrations,
which complicate risk assessment and the establishment of effective control
measures. The objective of this study was to obtain an insight into the actual
variation in acrylamide concentrations in French fries prepared under typical
conditions in a food service establishment (FSE). Besides acrylamide, frying
time, frying temperature, and reducing sugars were measured and the actual
practices at receiving, thawing and frying during French fries preparation were
observed and recorded. The variation in the actual frying temperature contributed
most to the variation in acrylamide concentrations, followed by the variation in
actual frying time; no obvious effect of reducing sugars was found. The lack of
standardised control of frying temperature and frying time (due to inadequate
frying equipment) and the variable practices of food handlers seem to contribute
most to the large variation and high acrylamide concentrations in French fries
prepared in a restaurant type of FSE as compared to chain fast-food services, and
institutional caterers. The obtained insights in this study can be used to
develop dedicated control measures in FSE, which may contribute to a sustainable
reduction in the acrylamide intake.
PMID- 26434273
TI - Determination of catechins and flavonol glycosides in Chinese tea varieties.
AB - A standardised profiling method based on high performance liquid chromatography
combined with ultraviolet (UV) and mass spectrometric detection (MS) was
established to analyse the phenolic compounds of selected tea varieties used for
manufacturing of green, black and oolong teas. The composition and content of 24
tea constituents were analysed, including catechins, flavonol and flavones
glycosides, phenolic acids and purine alkaloids. Each tea variety had a unique
chemical profile. The compositions of catechins were lower in the tea varieties
for green tea manufacturing, while the content of myricetin glycosides was the
lowest in the tea variety for oolong tea manufacturing. The content of individual
phenolic compounds in the selected tea varieties is highly variable. However, the
content of total catechins is proposed to be helpful to classify tea according to
the future application as non fermented green and fermented oolong or black tea.
PMID- 26434274
TI - Alterations in antioxidant enzyme activities and oxidative damage in alcoholic
rat tissues: protective role of Thespesia populnea.
AB - Recent advances in our understanding of the pathogenesis of alcohol-induced
hepato-renal injury and the development of new approaches to its treatment have
been reported in various works. This study involves alcohol-induced oxidative
stress linked to the metabolism of ethanol involving both mitochondrial and
peroxisomal fractions of liver and kidney. Alcohol treatment resulted in the
depletion of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
(GPx), glutathione reductase (GR), Glutathione-S-Transferase (GST) activities,
and reduced glutathione (GSH) content, higher level of malondialdehyde (MDA) and
lower levels of protein carbonyls (PC) causing malfunction of hepatic and renal
tissues, when compared to control rats. Thespesia populnea (TP) leaf extracts,
administered to chronic alcohol ingested rats, were envisaged to possess
significant antioxidant defence properties and help in the recovery of tissues
from alcohol-induced oxidative damage. The results showed that degenerative
changes in hepatic and renal cells of alcoholic groups were minimized by the
administration of TP leaf extracts as also revealed by histopathological
examination. The current findings indicate that treatment with TP extracts
reduces alcohol-induced oxidative stress, thereby protecting the hepatic and
renal tissue from alcohol-induced damage.
PMID- 26434275
TI - Vibrational spectroscopic analysis of hake (Merluccius merluccius L.) lipids
during frozen storage.
AB - Vibrational spectroscopy (mid FTIR and FT-Raman) was used to monitor lipids
extracted from hake fillets during frozen storage. Kramer shear resistance was
used as a marker of texture changes and lipid damage was also investigated by
following the development of conjugated dienes and free fatty acids by
spectrophotometric methods. Results show that the intensity of the free fatty
acid carboxylic nu(CO) band measured by ATR-FTIR spectroscopy can be used for
monitoring the development of lipid hydrolysis in hake lipids. Changes in the
Raman nu(CC) stretching region (1658cm(-1) band), partially attributed to
conjugated dienes development, were the only observed spectroscopic alterations
related to lipid oxidation of hake lipids during frozen storage at -10 degrees C.
The high correlation of free fatty acids with instrumental texture and the
disappearance of the nuas(PO2(-)) band are consistent with membrane lipid
hydrolysis being one of the factors directly related with toughening of lean fish
flesh.
PMID- 26434276
TI - Model studies on the role of 5-hydroxymethyl-2-furfural in acrylamide formation
from asparagine.
AB - This study aimed to investigate the mechanism of acrylamide formation during
heating asparagine (ASN) at elevated temperatures with glucose (GLC), and 5
hydroxymethyl-2-furfural (HMF). The results revealed that HMF rapidly reacted
with ASN, leading to acrylamide formation. The ASN-HMF model system generated
acrylamide more efficiently than the ASN-GLC model system during heating at 180
degrees C. A significantly higher amount of 3-aminopropionamide (3-APA) was
formed in the ASN-HMF model system than in the ASN-GLC model system within 5min
at 180 degrees C. The amount of 3-APA decreased after 5min of heating in both
model systems while the amount of acrylamide continued to increase in the ASN-HMF
model system. In-depth high resolution mass spectrometry analyses of reaction
products formed in the model systems together with the kinetic data suggested
that HMF is a potent carbonyl accelerating acrylamide formation during heating. 3
APA was found as one of the key intermediates leading to acrylamide formation.
PMID- 26434277
TI - Use of monoglyceride hydrogel for the production of low fat short dough pastry.
AB - The influence of palm oil replacement with a monoglyceride-palm oil-water gel
(hydrogel) on physical properties and acrylamide content of a low fat short dough
pastry was studied. The effect of the incorporation of the hydrogel was monitored
during storage by assessing moisture, firmness, proton density/mobility using
magnetic resonance imaging (MRI) and acrylamide content. The use of hydrogel
allowed the lipid content of pastries to be reduced with minor effects on their
quality characteristics. However, the hydrogel-containing pastries showed a
crunchier crust, higher acrylamide content and a higher tendency to staling. As
assessed by MRI, these results were ascribable to the development of a peculiar
system morphology promoted by hydrogel incorporation in the food matrix.
PMID- 26434278
TI - Antithrombotic activity of fractions and components obtained from raspberry
leaves (Rubus chingii).
AB - The 70% ethanol fraction from an aqueous extract of raspberry leaves was shown to
be the most antithrombotic fraction in in vitro and in vivo tests. The total
flavonoids and phenolics in this fraction were 0.286g/g and 0.518g/g by
colorimetry. Six compounds, including salicylic acid, kaempferol, quercetin,
tiliroside, quercetin 3-O-beta-d-glucopyranoside and kaempferol 3-O-beta-d
glucopyranoside, were isolated from the active fraction. Among them, kaempferol,
quercetin and tiliroside obviously delayed plasma recalcification time (PRT) in
blood.
PMID- 26434279
TI - Antidiabetic effect of Ficus racemosa Linn. stem bark in high-fat diet and low
dose streptozotocin-induced type 2 diabetic rats: a mechanistic study.
AB - The present study was designed to investigate the effects of the ethanol extract
of Ficus racemosa (FRE) on biochemical parameters in type 2-like diabetes,
induced by a combination of standardised high-fat diet and low-dose
streptozotocin (25mgkg(-1), i.p.) in rats. To elucidate the mode of action of
FRE, its effects on a battery of targets involved in glucose homeostasis was
evaluated. FRE (200 and 400mgkg(-1), p.o.), in a dose-dependent manner, altered
the biochemical parameters and significantly improved glucose tolerance and HDL-c
levels. In different bioassays, FRE showed inhibition of PTP-1B (IC50 12.1MUg/mL)
and DPP-IV (42.5%). FRE exhibited 82.6% binding to PPAR-gamma. Furthermore FRE
exhibited stimulation of glucose uptake by skeletal muscles (hemi-diaphragm).
Bergenin was quantified in bioactive-FRE by high-performance liquid
chromatography (0.15%w/w). This is the first report demonstrating the
effectiveness of F. racemosa stem bark in type 2 diabetes and targets involved in
it.
PMID- 26434280
TI - Rice alpha-globulin decreases serum cholesterol concentrations in rats fed a
hypercholesterolemic diet and ameliorates atherosclerotic lesions in
apolipoprotein E-deficient mice.
AB - The hypocholesterolemic and antiatherogenic effects of rice alpha-globulin remain
unclear. We investigated the hypocholesterolemic effect of rice alpha-globulin in
rats fed a hypercholesterolemic diet. The rats were divided into 4 groups and
were orally administrated the following three proteins or a vehicle for 4weeks:
rice protein, rice alpha-globulin, or soy beta-conglycinin at a dose of 100mg/kg
body weight or carboxymethylcellulose to the control rats. In the rice alpha
globulin group, serum cholesterol concentrations were 28% lower than the control
group and fecal neutral steroid excretion was increased by 30%. The
hypocholesterolemic effect of rice alpha-globulin was equal to soy beta
conglycinin in SD rats fed the hypercholesterolemic diet. However, the serum
cholesterol concentrations in the rice protein group did not change compared to
the control group. To investigate the antiatherogenic effects of rice alpha
globulin, male apolipoprotein E-deficient mice were orally administered the same
dose of rice alpha-globulin for 9weeks. The en face lesion area in the aorta was
46% lower than in the control group. In conclusion, administration of rice alpha
globulin improves hypercholesterolemia in rats fed a hypercholesterolemic diet by
increasing the fecal excretion of neutral sterols, and inhibits atherosclerosis
development in apolipoprotein E-deficient mice. The anti-atherosclerotic effect
exerts by mechanism(s) other than the regulation of serum MCP-1 and NO
concentrations.
PMID- 26434281
TI - Anti-angiogenic effects and mechanisms of zerumin A from Alpinia caerulea.
AB - Alpinia caerulea (R.Br.) Bentham, a perennial herb growing in tropical and
subtropical Australia, is used as a flavouring spice and a ginger substitute. Its
fruit has been used as indigenous food among the aboriginal Australians; 95%
ethanol extracts of the dried fruits, leaves, rhizomes and roots of this plant
were investigated in a zebrafish model by quantitative endogenous alkaline
phosphatase assay. Only the fruit extract showed potential anti-angiogenic
effect, inhibiting vessel formation by 25% at 20MUg/ml. Two diterpenoids were
isolated and identified as zerumin A and (E)-8(17),12-labdadiene-15,16-dial.
Zerumin A, which had mainly accumulated in the fruits and bearing a carboxylic
group, could dose-dependently inhibit vessel formation, in both wild-type and
Tg(fli1a:EGFP)y1 zebrafish embryos. The semi-quantitative reverse transcription
polymerase chain reaction assay on wild type zebrafish embryos suggested that
zerumin A affected multiple molecular targets related to angiogenesis. Further
investigation, by human umbilical vein endothelial cell assays, revealed that
zerumin A specifically inhibited the proliferation and migration steps, to
prevent angiogenesis progress.
PMID- 26434282
TI - Properties of Calanus finmarchicus biomass during frozen storage after heat
inactivation of autolytic enzymes.
AB - Calanus finmarchicus is a marine zooplankton of interest for the aquaculture
industry, as well as for nutraceuticals and the cosmetic industry. The chemical
composition of C. finmarchicus rapidly changes postmortem due to autolytic
processes; in particular phospholipids rapidly degrade to give free fatty acids.
The aim of this study was to inactivate autolytic enzymes in C. finmarchicus by
applying heat (72 degrees C, 5-30min) through mixing with boiling, fresh water,
and further to explore the effects of heat (70 degrees C, 15min) combined with
long time storage (-20 degrees C, 12months) of treated and untreated material.
Heat treatment (5min) inactivated all tested enzymes and maintained the initial
amount of phospholipids, total lipids and crude protein. Storage of untreated
material led to complete degradation of all phospholipids, whereas heat treatment
resulted in a stable product containing the initial amount of phospholipids and
astaxanthin.
PMID- 26434283
TI - Preparation of palm olein enriched with medium chain fatty acids by lipase
acidolysis.
AB - Medium chain (MC) fatty acids, caprylic (C8:0) and capric (C10:0) were
incorporated into palm olein by 1,3-specific lipase acidolysis, up to 36% and
43%, respectively, when added as mixtures or individually after 24h. It was found
that these acids were incorporated into palm olein at the expense of palmitic and
oleic acids, the former being larger in quantity and reduction of 18:2 was
negligible. The modified palm olein products showed reduction in higher molecular
weight triacylglycerols (TGs) and increase in concentration of lower molecular
weight TGs compared to those of palm olein. Fatty acids at sn-2 position in
modified products were: C10:0, 4%; C16:0, 13%; C18:1, 66%; and C18:2, 15.4%. DSC
results showed that the onset of melting and solids fat content were considerably
reduced in modified palm olein products and no solids were found even at and
below 10 degrees C and also the onset of crystallisation was considerably
lowered. The cloud point was reduced and iodine value dropped from 55.4 to 38 in
modified palm olein. Thus, nutritionally superior palm olein was prepared by
introducing MC fatty acids with reduced palmitic acid through lipase acidolysis.
PMID- 26434284
TI - Bioprospecting traditional Pakistani medicinal plants for potent antioxidants.
AB - Antioxidant potential of four methanol extracts from three selected plant
species, namely Salvia nubicola (Lamiaceae), Acer oblongifolium (Aceraceae) and
Hedera nepalensis (Araliaceae) was measured using assays in aqueous and lipid
systems. Antioxidant activities were investigated in aqueous systems by using
DPPH radical-scavenging assay, ABTS radical-scavenging assay and DNA protection
assay, while antioxidant activity in a lipid system was determined by using the
thiobarbituric acid-reactive substances (TBARS) assay. Additionally, the Folin
Ciocalteu method was used to measure total phenolic content. Methanol extracts of
leaves and flowers of S. nubicola showed the highest Trolox equivalent (TE)
values in the case of the DPPH assay, 2484+/-4.9mmol TE/g extract, as well as
total phenolic content, 139+/-0.2mg gallic acid equivalents/g extract. Three
fractions (A-C) of the methanol extract of S. nubicola leaves and flowers were
produced by semi-preparative HPLC. Fraction B was found to be the most active in
the DPPH radical-scavenging assay and had the highest total phenol content. HPLC
DAD and LC-MS revealed rosmarinic acid in S. nubicola extracts and chlorogenic
acid and rutin in H. nepalensis extracts as the main phenolic antioxidants.
PMID- 26434285
TI - Identification of ethyl 2-hydroxy-4-methylpentanoate in red wines, a compound
involved in blackberry aroma.
AB - The aroma profile of Bordeaux red wines is known to be marked by blackberry and
blackcurrant flavours; this study focused on the fresh blackberry aroma in
Bordeaux red wines, using sensory gas chromatography-olfactometry (GC-O) and two
dimensional gas chromatography analysis (GC-GC-MS). A previous HPLC fractionation
of red wine extracts on a C18 column produced four fractions with blackberry
aromas that were then analysed by GC-O, GC-GC-MS and GC-MS. From these fractions,
10 esters, corresponding to red- or black-berry fruit descriptors, were
characterised by GC-MS. Ethyl 2-hydroxy-4-methylpentanoate (ethyl leucate, EL)
was identified for the first time in red and white table wines as a compound
directly associated with a "fresh blackberry" aroma. Its perception thresholds
were 900 and 300MUg/l, respectively, in dearomatized red wine and model wine
solution (alcohol 12%, pH 3.5), and the average concentration in the various
wines was ~400MUg/l. Sensory omission tests highlighted the importance of this
compound and identified a perceptive interaction with ethyl butanoate.
PMID- 26434286
TI - Losses of nitrogen fractions from herring to brine during marinating.
AB - Fish meat is characterized by a high content of valuable nutrients. During the
marinating process, however, the process of proteins diffusion and other nitrogen
fractions from fish to the surrounding brine is commonly observed. It was
determined that the total nitrogen loss from herring meat of industrial maturity
(4-5day) amounted to 6-19% of raw material nitrogen. Extension of the marinating
time to 16-18days increases nitrogen losses even to 18-27%. Less loss was
observed during marinating of fresh than of frozen herring and during marinating
of carcasses, as opposite to fillets. Higher nitrogen content in fish was not
proved to influence higher nitrogen losses in a brine. The majority of loss
consisted of nitrogen fractions soluble in TCA, of which one third was formed by
alpha-amine nitrogen. Nitrogen contained in brine suspension accounted for only
1.5-4% of total nitrogen losses. With increasing salt or acid concentration the
amount of total nitrogen loss was lower from fresh herring and higher from frozen
one. Higher salt concentration significantly reduced the amount of non-protein
nitrogen and all its fractions during marinating of fresh and frozen herring. In
case of acetic acid, the influence of its concentration was diverse and depended
on type of herring and its dressing.
PMID- 26434287
TI - Antioxidant activity of a new phenolic glycoside from Lagenaria siceraria Stand.
fruits.
AB - The antioxidant properties of different extracts of Lagenaria siceraria (bottle
gourd) fruit were evaluated. In the process, a new phenolic glycoside (E)-4
hydroxymethyl-phenyl-6-O-caffeoyl-beta-d-glucopyranoside (1) was isolated and
identified together with 1-(2-hydroxy-4-hydroxymethyl)-phenyl-6-O-caffeoyl-beta-d
gluco-pyranoside (2), protocatechuic acid (3), gallic acid (4), caffeic acid (5)
and 3,4-dimethoxy cinnamic acid (6). Their structures were elucidated by
extensive NMR experiments including (1)H-(1)H (COSY) and (1)H-(13)C (HMQC and
HMBC) spectroscopy and chemical evidences. The antioxidant potential of the
compound 1 and 2 was tested in different in vitro assay systems such as free
radical scavenging assay, 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) reduction assay, superoxide scavenging activity, reducing power
assay and linoleic acid peroxidation assay.
PMID- 26434288
TI - Berberine, an isoquinoline alkaloid, inhibits streptozotocin-induced apoptosis in
mouse pancreatic islets through down-regulating Bax/Bcl-2 gene expression ratio.
AB - Diabetes may cause apoptosis in pancreatic islets. Berberine is an isoquinoline
alkaloid used for its pharmacological functions including anti-inflammation.
However, the berberine effect on pancreatic islets is still not clear. This study
is aimed at clarifying the protective mechanism in berberine against islet cell
apoptosis. This study established in vitro experimental models using
streptozotocin (STZ)-treated primary pancreatic islet cells from ICR mice to
unravel the protective mechanism of berberine on islets. The Bax/Bcl-2 (pro-/anti
apoptotic) genes expression in the islets was determined using real-time
quantitative polymerase chain reaction assay. The results showed that berberine
administration at one time or before STZ-stimulation significantly (P<0.05) down
regulated the Bax/Bcl-2 genes expression ratio, compared to those in STZ
treatment alone group. Our results suggest that berberine's anti-apoptotic effect
on pancreatic primary islets is through down-regulating the Bax/Bcl-2 genes
expression ratio in both concurrent and preventive manners.
PMID- 26434289
TI - The anticarcinogenic potential of essential oil and aqueous infusion from caper
(Capparis spinosa L.).
AB - The present study assessed the influence of essential oil and aqueous infusion
from wild-grown caper (Capparis spinosa L.) on cell growth, NF-kappaB activation,
apoptosis and cell cycle in the human colon carcinoma cell line, HT-29. Methyl
isothiocyanate (92.06%), a degradation product of glucosinolate glucocapparin,
was detected as major component of essential oil from caper leaves and flower
buds. Aqueous infusion of caper showed an interesting and variegate compositional
pattern containing several phenolic compounds, among which a flavonol glycoside,
rutin (quercetin 3-O-rutinoside, 50.7%) and 5-caffeoyl-quinic acid (chlorogenic
acid, 17.5%) were detected as dominant. Caper essential oil and aqueous infusion
showed time- and dose-dependent high inhibitory effect on HT-29 cell
proliferation. In addition, they induced the inhibition on nuclear factor kappaB
(NF-kappaB) activity in a dose-dependent manner, while they did not show any
effect on apoptosis in HT-29 cells. Flow cytometric analysis indicated that
treatment with caper essential oil and aqueous infusion resulted in G2/M cell
cycle arrest in a dose-dependent manner. Presented results suggest that caper
contains volatile and non-volatile compounds which potentially can play an
important role in colon cancer prevention.
PMID- 26434290
TI - Preparative separation and purification of Rebaudioside A from Stevia rebaudiana
Bertoni crude extracts by mixed bed of macroporous adsorption resins.
AB - The separation and purification of Rebaudioside A (RA) from Stevia rebaudiana
Bertoni crude extracts (Steviosides) by macroporous adsorption resin (MAR) mixed
bed were systematically investigated. MAR mixed bed of HPD750-LSA40-LSA30-DS401
was selected due to its better separation degree. Based on the
kinetics/thermodynamics experiment of the mixed bed, it was found that the
experimental data fitted better to the pseudo-second-order model, and intra
particle diffusion was rate-limiting step. The adsorption isotherm was consistent
with IV equilibrium adsorption isotherm classified by Brunauer. Furthermore, the
influencing factors for the separation of RA based on HPLC were also
investigated. Under the optimal conditions, the separation degree for RA (DAS)
increased from 0.771 to 1.54. Moreover, the experimental results showed that the
purity of the obtained product increased from 60% to 97%.
PMID- 26434291
TI - Effect of fermentation time and drying temperature on volatile compounds in
cocoa.
AB - The effects of fermentation time and drying temperature on the profile of
volatile compounds were evaluated after 2, 4, 6, and 8 fermentation days followed
by drying at 60, 70 and 80 degrees C. These treatments were compared with dry
cocoa controls produced in a Samoa drier and by a sun-drying process. A total of
58 volatile compounds were identified by SPME-HS/GC-MS and classified as: esters
(20), alcohols (12), acids (11), aldehydes and ketones (8), pyrazines (4) and
other compounds (3). Six days of fermentation were enough to produce volatile
compounds with flavour notes desirable in cocoa beans, as well as to avoid the
production of compounds with off-flavour notes. Drying at 70 and 80 degrees C
after six fermentation days presented a volatile profile similar to the one
obtained by sun drying. However, drying at 70 degrees C represents a lower cost.
Given the above results, in the present study the optimal conditions for
fermentation and drying of cocoa beans were 6days of fermentation, followed by
drying at 70 degrees C.
PMID- 26434292
TI - Pharmacokinetic study of mangiferin in human plasma after oral administration.
AB - Mangiferin, an active component of traditional Chinese herbal medicine, although
it is reported to have various pharmacological effects, the limited number of
pharmacokinetic studies limit its wide application. To evaluate the
pharmacokinetics of mangiferin in human, a sensitive high performance liquid
chromatography-mass spectrometry (HPLC-MS) method for the determination of
mangiferin in human plasma was developed. The proposed HPLC-MS method is
selective, precise and accurate enough and enables the identification and
quantification of mangiferin for the use in clinical studies. After single oral
administration of 0.1, 0.3 and 0.9g mangiferin, respectively, the method was
successfully applied for the pharmacokinetics of mangiferin in 21 healthy male
Chinese volunteers. The pharmacokinetic of mangiferin was fit to the non
compartmental model. The pharmacokinetics parameters were calculated. Mangiferin
concentration in plasma reached 38.64+/-6.75ng/mL about 1h after oral
administration of 0.9g mangiferin and the the apparent elimination half-life
(t1/2) was 7.85+/-1.72h. The absorption of mangiferin was increased with the
administration of a large dose and it was concluded that the pharmacokinetics of
mangiferin in human was nonlinear.
PMID- 26434293
TI - Antifungal nortriterpene and triterpene glycosides from the sea cucumber
Apostichopus japonicus Selenka.
AB - A nortriterpene glycoside, 26-nor-25-oxo-holotoxin A1 (1), four triterpene
glycosides, including both holostane and non-holostane types analogues,
holotoxins D-G (2-5), together with three known triterpene glycosides, holotoxins
A1 and B (6, 7), and cladoloside B (8), were isolated from the warty sea cucumber
Apostichopus japonicus Selenka, a traditional tonic with high economic value in
China. The structures of the new compounds were elucidated by a combination of
detailed spectroscopic analysis and chemical methods. This is the first report of
a nortriterpene glycoside isolated from sea cucumbers. These compounds showed
potent antifungal activities in the in vitro biotest. A preliminary structure
activity analysis suggests that the 18(20) lactone group and the Delta(25)
terminal double bond may increase the activity. The component of the carbohydrate
chain seems play an important role whereas the double bond transformation from
Delta(9(11)) to Delta(7) in the aglycone moiety contributes little to the
bioactivity.
PMID- 26434294
TI - A taste of sweet pepper: Volatile and non-volatile chemical composition of fresh
sweet pepper (Capsicum annuum) in relation to sensory evaluation of taste.
AB - In this study volatile and non-volatile compounds, as well as some breeding
parameters, were measured in mature fruits of elite sweet pepper (Capsicum
annuum) lines and hybrids from a commercial breeding program, several cultivated
genotypes and one gene bank accession. In addition, all genotypes were evaluated
for taste by a trained descriptive sensory expert panel. Metabolic contrasts
between genotypes were caused by clusters of volatile and non-volatile compounds,
which could be related to metabolic pathways and common biochemical precursors.
Clusters of phenolic derivatives, higher alkanes, sesquiterpenes and lipid
derived volatiles formed the major determinants of the genotypic differences.
Flavour was described with the use of 14 taste attributes, of which the texture
related attributes and the sweet-sour contrast were the most discriminatory
factors. The attributes juiciness, toughness, crunchiness, stickiness, sweetness,
aroma, sourness and fruity/apple taste could be significantly predicted with
combined volatile and non-volatile data. Fructose and (E)-2-hexen-1-ol were
highly correlated with aroma, fruity/apple taste and sweetness. New relations
were found for fruity/apple taste and sweetness with the compounds p-menth-1-en-9
al, (E)-beta-ocimene, (Z)-2-penten-1-ol and (E)-geranylacetone. Based on the
overall biochemical and sensory results, the perspectives for flavour improvement
by breeding are discussed.
PMID- 26434295
TI - Effect of cholestin on toxicity of vitamin A in rats.
AB - A study was undertaken to investigate the effect of cholestin on the toxicity of
vitamin A in male wistar rats. The rats were divided into six groups and fed
different diets with or without supplement of 1% cholestin and 25,000-50,000 (IU)
vitamin A for 2 months. Hence, the symptoms of vitamin A toxicity in rats
included loss of body weight, hepatotoxicity and nephrotoxicity. However, these
toxic effects of vitamin A were significantly reduced when the rats fed a diet
supplemented with cholestin. Furthermore, the level of vitamin A in the serum of
rats treated with cholestin and vitamin A was higher than that of the rats
treated with vitamin A alone. It indicated that cholestin might play a role in
reducing the toxic effect of vitamin A in rats.
PMID- 26434296
TI - Physicochemical properties and oral bioavailability of ursolic acid nanoparticles
using supercritical anti-solvent (SAS) process.
AB - The objective of the study was to prepare ursolic acid (UA) nanoparticles using
the supercritical anti-solvent (SAS) process and evaluate its physicochemical
properties and oral bioavailability. The effects of four process variables,
pressure, temperature, drug concentration and drug solution flow rate, on drug
particle formation during SAS process, were investigated. Particles with mean
particle size ranging from 139.2+/-19.7 to 1039.8+/-65.2nm were obtained by
varying the process parameters. The UA was characterised by scanning electron
microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, thermal
gravimetric analysis, specific surface area, dissolution test and bioavailability
test. It was concluded that physicochemical properties and bioavailability of
crystalline UA could be improved by physical modification, such as particle size
reduction and generation of amorphous state using SAS process. Further, SAS
process was a powerful methodology for improving the physicochemical properties
and bioavailability of UA.
PMID- 26434297
TI - One-step separation of beta-galactosidase from beta-lactoglobulin using water-in
oil microemulsions.
AB - Solubilisation of beta-galactosidase from Kluyveromyces lactis in Aerosol-OT
water-in-isooctane microemulsions was measured as a function of buffer type and
concentration, pH, and protein concentration. For buffer concentrations above
~40mM, the enzyme was largely excluded from the droplets. Based on these results,
a one-step separation was developed. A protein-containing aqueous feed was
injected into an AOT/isooctane solution, with the feed volume slightly in excess
of the predicted water solubility. Impurity proteins were entrapped inside the
microemulsion droplets that then formed in the organic phase, while the high MW
target protein was excluded and entered a newly formed, excess aqueous phase. The
separation of beta-galactosidase from the test protein beta-lactoglobulin was
most complete at 100mM KCl salt concentration, where the droplets were large
enough to carry beta-lactoglobulin but too small for beta-galactosidase. At 100mM
[KCl], 92% of the total enzyme activity was recovered in a concentrated and
virtually pure form.
PMID- 26434298
TI - Evaluation of the total oxidant scavenging capacity of saponins isolated from
Platycodon grandiflorum.
AB - The antioxidant activity of saponins isolated from Platycodon grandiflorum (PG;
Balloon flower) was determined using the total oxidant-scavenging capacity (TOSC)
assay. Platycodigenin, polygalacic acid, platycodin D, platycoside E and
deapioplatycoside E were isolated and their structures were characterised based
on their physical and spectral properties and by comparison of these results with
similar data in the literature. Platycodin D showed the greatest TOSC value
against peroxyl radicals, followed (in decreasing order) by polygalacic acid,
platycodigenin, deapioplatycosides E and platycoside E. Although the TOSC value
of the saponins against peroxyl radicals was less than that of glutathione (GSH)
and Trolox used as positive controls. However, TOSC value of platycodigenin,
deapioplatycoside E, platycodin D or platycoside E against peroxynitrite was 2.35
, 1.27-, 1.02- or 0.75-fold of GSH, respectively, while polygalacic acid
exhibited no scavenging capacity of peroxynitrites. These results suggest
importance of the presence of hydroxyl group at carbon 24 in platycodigenin in
peroxynitrite scavenging. As the number of attached sugar residues in the saponin
glycosides is increased, the scavenging capacity of peroxyl radical, but not
peroxynitrite was significantly decreased. These results showed that PG saponins
have potent antioxidant activities, which is different according to the structure
of aglycones and the number of attached sugar residues.
PMID- 26434299
TI - Structural characterisation and anti-ageing activity of extracellular
polysaccharide from a strain of Lachnum sp.
AB - A homogeneous extracellular polysaccharide of Lachnum YM261(LEPS-1) with a
molecular weight of 21670Da was characterised. According to HPGPC, IR, periodate
oxidation and Smith degradation, GC-MS and (1)H NMR analysis, the results
indicated that LEPS-1 was a glucan linked by the beta-(1->3)-d-pyran glycosidic
bond. The effect of LEPS-1 on anti-ageing in d-gal model mice was also studied.
It was found that LEPS-1 significantly increased the activities of antioxidant
enzymes (i.e. SOD superoxide dismutase, CAT catalase, GSH-PX glutathione
peroxidase) and decreased malondialdehyde (MDA) content in liver, brain and serum
of d-gal model mice. These results showed that LEPS-1 had a strong anti-ageing
activity.
PMID- 26434300
TI - Development of oxidised and heat-moisture treated potato starch film.
AB - This study investigated the effects of sodium hypochlorite oxidation and a heat
moisture treatment of potato starch on the physicochemical, pasting and textural
properties of potato starches in addition to the water vapour permeability (WVP)
and mechanical properties of potato starch films produced from these starches.
The carbonyl contents, carboxyl contents, swelling power, solubility, pasting
properties and gel texture of the native, oxidised and heat-moisture treated
(HMT) starches were evaluated. The films made of native, oxidised and HMT
starches were characterised by thickness, water solubility, colour, opacity,
mechanical properties and WVP. The oxidised and HMT starches had lower viscosity
and swelling power compared to the native starch. The films produced from
oxidised potato starch had decreased solubility, elongation and WVP values in
addition to increased tensile strength compared to the native starch films. The
HMT starch increased the tensile strength and WVP of the starch films compared to
the native starch.
PMID- 26434301
TI - Implementation of response surface methodology to assess the antiradical
behaviour in mixtures of ascorbic acid and alpha-tocopherol with grape (Vitis
vinifera) stem extracts.
AB - The efficiency of grape stem extracts to express antiradical activity was
assessed using two different approaches and DPPH as the radical probe. In
addition, the mixture effects when the extracts were combined with ascorbic acid
(AA) and alpha-tocopherol (alpha-Tcp) were also evaluated. The approaches
included a simple linear regression analysis between the response (antiradical
activity) and concentration, but also a response surface methodology, which
permitted the monitoring of the response upon simultaneous variation of both the
concentration of the total polyphenols of the extracts and either of the
antioxidants (AA and alpha-Tcp). The deployment of linear regression poses
important constraints with regard to concentration ranges, whereas response
surface methodology might be a valuable statistical tool for similar assessments
and credible modelling of binary mixtures of antioxidants. In all combinations
tested it was found that an antagonism was manifested, presumably as a result of
AA and alpha-Tcp regeneration by the extract polyphenols, at the expense of the
latter.
PMID- 26434302
TI - Heat and pressure treatments effects on peanut allergenicity.
AB - Peanut allergy is recognized as one of the most severe food allergies. The aim of
this study was to investigate the changes in IgE binding capacity of peanut
proteins produced by thermal-processing methods, including autoclaving.
Immunoreactivity to raw and thermally processed peanut extracts was evaluated by
IgE immunoblot and skin prick test in patients with clinical allergy to peanut.
Roasted peanut and autoclaved roasted peanut were selected for IgE ELISA
experiments with individual sera, immunoblot experiments with antibodies against
peanut allergens (Ara h 1, Ara h 2 and Ara h 3), digestion experiments, and
circular dichroism spectroscopy. In vitro and in vivo experiments showed IgE
immunoreactivity of roasted peanut proteins decreased significantly at extreme
conditions of autoclaving. Circular dichroism experiments showed unfolding of
proteins in autoclave treated samples, which makes them more susceptible to
digestion. Autoclaving at 2.56atm, for 30min, produces a significant decrease of
IgE-binding capacity of peanut allergens.
PMID- 26434303
TI - Effect of low-dose irradiation on biogenic amines formation in vacuum-packed
trout flesh (Oncorhynchus mykiss).
AB - The effects of vacuum packaging followed by high-energy electron beam irradiation
on the shelf-life of fillets of rainbow trout (Oncorhynchus mykiss) were
examined. Samples were irradiated at doses of 0.25, 0.50, 0.75, 1.0 and 2.0kGy.
The control and treated packs were stored at 3.5 degrees C for up to 28, 42, 70
and 98days (control - 0, 0.25, 0.50 and >0.50kGy respectively). The content of
seven biogenic amines (putrescine, cadaverine, spermidine, spermine, histamine,
tyramine and tryptamine) were determined. Putrescine, cadaverine and tyramine
showed very good correspondence with the irradiation dose and organoleptic
properties. Samples of good quality contained less than 10mg/kg of each of these
amines. The polyamines spermidine and spermine did not show statistically
significant changes with the irradiation dose and the time of storage. With few
exceptions, histamine was not detected in the samples treated with radiation.
Tryptamine was not detected in any of the samples.
PMID- 26434304
TI - Effect of moisture content on selected physicochemical properties of two
commercial hen egg white powders.
AB - After short-term storage at 23 degrees C, selected physicochemical properties of
two hen egg white powders (with and without hydrolysis) were studied. Overall,
the effect of moisture content on physicochemical properties of Hydrolysed Egg
White powder (HEW) was more severe than those of Dried Egg White powder (DEW).
The denaturation temperature (Td) and its enthalpy change (DeltaHd) of ovalbumin
in DEW followed an exponential model, as well as the Td of HEW. The Gordon-Taylor
equation modelled well the glass transition temperatures (Tg) of HEW and DEW. The
Guggenheim-Anderson-de Boer (GAB) model fitted well to the type II moisture
sorption isotherm. At the critical moisture content (12.0%, dry basis), compared
with DEW, the colour of HEW began to darken dramatically and its hardness started
to change significantly. These changes were closely related to the inherent
characteristics of the two products. The mechanisms relevant to these
physicochemical changes were discussed.
PMID- 26434305
TI - Inhibition of aldose reductase and anti-cataract action of trans-anethole
isolated from Foeniculum vulgare Mill. fruits.
AB - Foeniculum vulgare fruits are routinely consumed for their carminative and mouth
freshening effect. The plant was evaluated for aldose reductase inhibition and
anti-diabetic action. Bioguided fractionation using silica gel column
chromatography, HPLC, and GC-MS analysis revealed trans-anethole as the bioactive
constituent possessing potent aldose reductase inhibitory action, with an IC50
value of 3.8MUg/ml. Prolonged treatment with the pet ether fraction of the F.
vulgare distillate demonstrated improvement in blood glucose, lipid profile,
glycated haemoglobin and other parameters in streptozotocin-induced diabetic
rats. Trans-anethole could effectively show anti-cataract activity through the
increase in soluble lens protein, reduced glutathione, catalase and SOD activity
on in vitro incubation of the eye lens with 55mM glucose. Trans-anethole
demonstrated noncompetitive to mixed type of inhibition of lens aldose reductase
using Lineweaver Burk plot.
PMID- 26434306
TI - Binding of divalent metal ions to 1-25 beta-caseinophosphopeptide: an isothermal
titration calorimetry study.
AB - To better understand the mechanism of metal ion transport through the
gastrointestinal tract to their absorption sites, isothermal titration
calorimetry (ITC) was used to investigate the binding of dicationic metals to
beta-CN(1-25)4P, a beta-casein tetraphosphorylated peptide. ITC technology was
found suitable for studying weak bonds between metal ions and phosphopeptides and
provided a direct means of thermodynamic and stoichiometric characterisation of
complex formation. Thus, one mole of beta-CN(1-25)4P binds two moles of Ca(2+),
Mg(2+) or Zn(2+) under experimental conditions close to those of the ileum (pH 8,
37 degrees C), with rather low binding affinity constants (K=4900-11,200M(-1)).
These low affinities should facilitate the release of metal ions during
intestinal absorption. By contrast, Cu(2+) did not bind to beta-CN(1-25)4P at pH
8, despite its reported significant affinity towards beta-casein and the 1-25
peptide at near-neutral pH.
PMID- 26434307
TI - Effect of cultural system and essential oil treatment on antioxidant capacity in
raspberries.
AB - The effects of cultural system and essential oil treatment on antioxidant
capacities in raspberries were evaluated. Raspberries were hand-harvested from
organic and conventional farms in Maryland, USA, and were treated with essential
oil including carvacrol, anethole, cinnamic acid, perillaldehyde, cinnamaldehyde,
and linalool. Results from this study showed that raspberries grown from organic
culture exhibited higher value of antioxidant capacities and individual
flavonoids contents. Moreover, the organic culture also enhanced the activities
of antioxidant enzymes. In addition, essential oil treatments promoted the
antioxidant enzymes activities and antioxidant capacities of raspberries, and the
most effective compound was perillaldehyde. In conclusion, raspberries produced
from organic culture contained significantly higher antioxidant capacities than
those produce from conventional culture. Postharvest essential oil treatments
have positive effect on enhancing antioxidant capacities in raspberries from both
organic and conventional cultures.
PMID- 26434308
TI - Phenolic profile and antioxidant activities of olive mill wastewater.
AB - Olive trees play an important role in the Moroccan agro-economy, providing both
employment and export revenue. However, the olive oil industry generates large
amounts of wastes and wastewaters. The disposal of these polluting by-products is
a significant environmental problem that needs an adequate solution. On one hand,
the phytotoxic and antimicrobial effects of olive mill wastewaters are mainly due
to their phenolic content. The hydrophilic character of the polyphenols results
in the major proportion of natural phenols being separated into the water phase
during the olive processing. On other hand, the health benefits arising from a
diet containing olive oil have been attributed to its richness in phenolic
compounds that act as natural antioxidants and are thought to contribute to the
prevention of heart diseases and cancers. Olive mill wastewater (OMW) samples
have been analysed in terms of their phenolic constituents and antioxidant
activities. The total phenolic content, flavonoids, flavanols, and
proanthocyanidins were determined. The antioxidant and radical scavenging
activity of phenolic extracts and microfiltred samples was evaluated using
different tests (iron(II) chelating activity, total antioxidant capacity, DPPH
assays and lipid peroxidation test). The obtained results reveal the considerable
antioxidant capacity of the OMW, that can be considered as an inexpensive
potential source of high added value powerful natural antioxidants comparable to
some synthetic antioxidants commonly used in the food industry.
PMID- 26434309
TI - Role of carbohydrases on the release of reducing sugar, total phenolics and on
antioxidant properties of oat bran.
AB - Aqueous solutions of medium oat bran flour were treated with four carbohydrases
viscozyme, celluclast, alpha-amylase, and amyloglucosidase, and then extracted
with equal volume of methanol. The resulting extracts were examined for their
reducing sugar content, total phenolic content (TPC), oxygen radical scavenging
absorbance capacity (ORAC), hydroxyl radical scavenging effect, superoxide
scavenging activity, and ferrous ion chelating potential. The amount of reducing
sugar increased form 2.0% in the control sample to 21.4% in the sample treated
with four fungal beta-glucanase units/g of bran. The increase in reducing sugar
was also associated with subsequent increase of other extractable compounds. The
total phenolic content as measured by Folin-Ciocalteu's method ranged from 0.50
to 4.80mg of gallic acid equivalents/g of bran, whereas the ORAC values were 14.4
25.4MUM of Trolox equivalents/g of bran. All the samples treated with
carbohydrases had higher TPC content and higher ORAC values than the control
sample (no enzyme treatment). In the hydroxyl radical scavenging assay, except
for the alpha-amylase treated sample, all other samples demonstrated a greater
inhibition power than the control. These results indicated that pre-treatment of
oat bran with cell wall degrading enzymes (i.e. carbohydrases) is a way to
increase the amount of extracted phenols as well as the antioxidant properties of
oat bran samples.
PMID- 26434310
TI - Characterisation and cooperative antimicrobial properties of chitosan/nano-ZnO
composite nanofibrous membranes.
AB - Chitosan was combined with nano-ZnO to increase its antimicrobial activity, using
polyvinyl alcohol as a support, and then were electronspun to form composite
nanofibres. Through SEM, EDX and XRD observations, chitosan was seen to be able
to incorporate nano-ZnO in the composite nanofibres. Escherichia coli, expressing
recombinant enhanced green fluorescent protein, and Candida albicans were used to
test the antimicrobial efficacy of the newly synthesised chitosan/nano-ZnO
antimicrobial composite. The CdTe quantum dots were used to rapidly detect the
residual changes of C. albicans and determine the end point of using
antimicrobial agents. Minimal minimum inhibitory concentration (MIC), post
antibiotic effect and continuous agent effect of the composite were determined.
The MIC of chitosan/nano-ZnO against C. albicans was 160MUg/ml, close to the
concentration of the treated composite with the lowest fluorescence intensity.
The cell damage was observed by SEM, which indicated that nano-ZnO in the
nanofibrous membranes played a cooperative role in the antimicrobial process of
chitosan.
PMID- 26434312
TI - Cytotoxic phenylpropanoid glycosides from Fagopyrum tataricum (L.) Gaertn.
AB - Fagopyrum tataricum (L.) Gaertn (tartary buckwheat) is an ancient dicotyledonous
crop belonging to Polygonaceae family. Besides its benefits for human
consumption, tartary buckwheat is also an important folk medicine in China for
its antioxidant, antitumour, hypotensive, hypoglycaemic and hypolipidaemic
activities. Phytochemical investigation of the ethyl acetate fraction of tartary
buckwheat roots led to the isolation of seven new phenylpropanoid glycosides,
tatarisides A-G (1-7), together with a known phenylpropanoid glycoside, diboside
A (8). Their structures were elucidated by means of spectroscopic methods. All
compounds (1-8) were evaluated for their cytotoxic activity against four human
cancer cell lines (A-549, HCT116, ZR-75-30 and HL-60). Tatariside C (3) was the
most active compound with IC50 values of 6.44-7.49MUg/ml against the four tested
cell lines.
PMID- 26434311
TI - Prebiotic effect of diosgenin, an immunoactive steroidal sapogenin of the Chinese
yam.
AB - This study investigated the effect of diosgenin, a yam-derived phytochemical, on
the growth of enteric lactic acid bacteria (LAB). The in vivo effect of diosgenin
on the density of intestinal flora was examined in a murine model of food
allergy. Oral administration with diosgenin markedly restored the diminished
density of faecal LAB associated with allergic reactions. The direct effect of
diosgenin and several structure-related steroidal compounds on the growth of
faecal anaerobes isolated from diosgenin-administered mice was also investigated.
The presence of diosgenin significantly enhanced the growth of Lactobacillus
murinus and Lactobacillus reuteri, but not enterococci. Structure-activity
relationship analysis showed that the prebiotic activity of steroidal sapogenins
might require structural elements of the C5-C6 double bond and intact E- and F
rings. Collectively, these results indicate that steroidal sapogenins may be a
novel class of prebiotics to LAB.
PMID- 26434313
TI - Stability of avocado oil during heating: comparative study to olive oil.
AB - The stability of the saponifiable and unsaponifiable fractions of avocado oil,
under a drastic heating treatment, was studied and compared to that of olive oil.
Avocado and olive oil were characterised and compared at time 0h and after
different times of heating process (180 degrees C). PUFA/SFA (0.61 at t=0) and
omega-6/omega-3 (14.05 at t=0) were higher in avocado oil than in olive oil
during the whole experiment. Avocado oil was richer than olive oil in total
phytosterols at time 0h (339.64; 228.27mg/100g) and at 9h (270.44; 210.30mg/100g)
of heating. TBARs was higher in olive oil after 3h, reaching the maximum values
in both oils at 6h of heating treatment. Vitamin E was higher in olive oil (35.52
vs. 24.5mg/100g) and it disappeared earlier in avocado oil (at 4 vs. 5h). The
stability of avocado oil was similar to that of olive oil.
PMID- 26434314
TI - Temperature and water loss affect ADH activity and gene expression in grape berry
during postharvest dehydration.
AB - Clusters of Aleatico wine grape were picked at 18 degrees Brix and placed at 10,
20, or 30 degrees C, 45% relative humidity (RH) and 1.5m/s of air flow to
dehydrate the berries up to 40% of loss of initial fresh weight. Sampling was
done at 0%, 10%, 20%, 30%, and 40% weight loss (wl). ADH (alcohol dehydrogenase)
gene expression, enzyme activity, and related metabolites were analysed. At 10
degrees C, acetaldehyde increased rapidly and then declined, while ethanol
continued to rise. At 20 degrees C, acetaldehyde and ethanol increased
significantly with the same pattern and declined at 40%wl. At 30 degrees C,
acetaldehyde did not increase but ethanol increased rapidly already at 10%wl. At
the latter temperature, a significant increase in acetic acid and ethyl acetate
occurred, while at 10 degrees C their values were low. At 30 degrees C, the ADH
activity (ethanol to acetaldehyde direction), increased rapidly but acetaldehyde
did not rise because of its oxidation to acetic acid, which increased together
with ethyl acetate. At 10 degrees C, the ADH activity increased at 20%wl and
continued to rise even at 40%wl, meaning that ethanol oxidation was delayed. At
20 degrees C, the behaviour was intermediate to the other temperatures. The
relative expression of the VvAdh2 gene was the highest at 10 degrees C already at
10%wl in a synchrony with the ADH activity, indicating a rapid response likely
due to low temperature. The expression subsequently declined. At 20 and 30
degrees C, the expression was lower and increased slightly during dehydration in
combination with the ADH activity. This imbalance between gene expression and ADH
activity at 10 degrees C, as well as the unexpected expression of the carotenoid
cleavage dioxygenase 1 (CCD1) gene, opens the discussion on the stress
sensitivity and transcription event during postharvest dehydration, and the
importance of carefully monitoring temperature during dehydration.
PMID- 26434315
TI - Analysis of indole compounds in edible Basidiomycota species after thermal
processing.
AB - Methanolic extracts of processed fruiting bodies of six edible mushroom species
(Basidiomycota) -Armillaria mellea, Boletus badius, Boletus edulis, Cantharellus
cibarius, Lactarius deliciosus collected from natural habitats and Pleurotus
ostreatus of commercial origin - were analysed for the presence of non
hallucinogenic indole compounds. Thermal processing was designed in such a way
that it mimicked conditions used for cooking of mushroom dishes, since only a
narrow group of mushrooms can be eaten raw, while indole compounds are
thermolabile. All processed extracts were shown to contain l-tryptophan (up to
8.92mg/100g dw). The contents of the remaining compounds, 5-methyltryptophan,
tryptamine, melatonin, indoleacetonitrile and indole, varied in different species
(from 0.71 to 6.55mg/100g dw). Extract of processed C. cibarius fruiting bodies
contained l-tryptophan, 5-methyltryptophan, tryptamine, melatonin,
indoleacetonitrile and indole (1.96-4.94mg/100g dw) whereas l-tryptophan
(2.78mg/100g dw) and tryptamine (2.77mg/100g dw) were the only indole compounds
identified in the processed fruiting bodies of A. mellea.
PMID- 26434316
TI - Regulation of lipid disorders by ethanol extracts from Zingiber zerumbet in high
fat diet-induced rats.
AB - The aim of this study was to investigate the antihyperlipidaemic effects of the
ethanol extract of Zingiber zerumbet (L) Smith (EEZZ). After being fed a high-fat
diet (HFD) for 2weeks, rats were dosed orally with EEZZ (100, 200 or 300mg/kg) or
fenofibrate (100mg/kg) once daily for 8weeks. EEZZ (300mg/kg/day) produced
effects similar to fenofibrate in reducing body weight gain, visceral fat-pad
weights and plasma lipid levels. EEZZ caused reductions in hepatic triglyceride
and cholesterol content, and lowered hepatic lipid droplet accumulation and the
size of epididymal adipocytes. HFD-induced reductions in the hepatic proteins of
peroxisome proliferator-activated receptor (PPAR) alpha, acyl-CoA oxidase (ACO)
and cytochrome P450 isoform 4A1 (CYP4A1) were reversed by EEZZ. These results
suggest that EEZZ reduced the accumulation of visceral fat and improved
hyperlipidaemia in HFD-fed rats by increasing fatty acid oxidation, an effect
which is likely to be mediated via up-regulation of hepatic PPARalpha.
PMID- 26434318
TI - Malting revisited: Germination of barley (Hordeum vulgare L.) is inhibited by
both oxygen deficiency and high carbon dioxide concentrations.
AB - During malting, barley (Hordeum vulgare L.) seeds are germinated to promote the
mobilisation of storage compounds. Germination is strongly influenced by O2 and
CO2; however, any distinction between the particular effects is missing. Since,
in this study, the ambient O2 concentration was maintained when high CO2
concentrations were applied, for the first time the impacts of CO2 and of O2
deficiency could be distinguished unambiguously. Germination was inhibited by
both O2 deficiency and high CO2 (80%) concentrations, documented by the lack of
any growth of coleoptiles and any increase of alpha-amylase and beta-glucanase
activity. In contrast, the related impacts of O2 starvation and high CO2 on
fermentation differ strongly, demonstrated by quite different patterns of ethanol
emission. Additionally, the stress metabolism - monitored by the means of GABA
accumulation - was also differently impacted. The elucidation of the underlying,
so far unknown, mechanisms will provide novel opportunities to improve malting.
PMID- 26434317
TI - Low molecular weight flaxseed protein-derived arginine-containing peptides
reduced blood pressure of spontaneously hypertensive rats faster than amino acid
form of arginine and native flaxseed protein.
AB - Flaxseed protein isolate (FPI) contains high amount of arginine, which plays
important physiological roles especially as nitric oxide precursor in the
vascular endothelium. Arginine-rich peptides can be generated from FPI and used
as a source of nitric oxide, which can produce in vivo vasodilatory effects
during hypertension. Enzymatic hydrolysis of FPI with trypsin and pronase
resulted in a hydrolysate that was fractionated using electrodialysis
ultrafiltration (EDUF). EDUF experiment resulted in migration of peptides to the
anionic and cationic recovery compartments. Compared to FPI with 11% arginine,
about one-third of the cationic fraction was composed of arginine. Thirteen
potential peptide sequences were identified to be present in the cationic
compartment of which 12 contained at least one arginine residue. None of the
peptides identified from the anionic compartment contained arginine. Oral
administration of the cationic peptides (200mg/kgbodywt.) to spontaneously
hypertensive rats resulted in a more rapid decrease in systolic blood pressure
when compared to similar amounts of FPI or the amino acid form of arginine. It
was concluded that the rapid effect of the arginine-rich peptide product suggests
faster rate of peptide absorption than amino acids and this may be exploited to
provide fast relief from hypertension.
PMID- 26434319
TI - Clitocybe alexandri extract induces cell cycle arrest and apoptosis in a lung
cancer cell line: Identification of phenolic acids with cytotoxic potential.
AB - Mushrooms are a possible rich source of biologically active compounds with the
potential for drug discovery. The aim of this work was to gain further insight
into the cytotoxicity mechanism of action of Clitocybe alexandri ethanolic
extract against a lung cancer cell line (NCI-H460 cells). The effects on cell
cycle profile and levels of apoptosis were evaluated by flow cytometry, and the
effect on the expression levels of proteins related to cellular apoptosis was
also investigated by Western blot. The extract was characterised regarding its
phenolic composition by HPLC-DAD, and the identified compounds were studied
regarding their growth inhibitory activity, by sulforhodamine B (SRB) assay. The
effect of individual or combined compounds on viable cell number was also
evaluated using the Trypan blue exclusion assay. It was observed that the C.
alexandri extract induced an S-phase cell cycle arrest and increased the
percentage of apoptotic cells. In addition, treatment with the GI50 concentration
(concentration that was able to cause 50% of cell growth inhibition; 24.8MUg/ml)
for 48h caused an increase in the levels of wt. p53, cleaved caspase-3 and
cleaved poly (ADP-ribose) polymerase (PARP). The main components identified in
this extract were protocatechuic, p-hydroxybenzoic and cinnamic acids. Cinnamic
acid was found to be the most potent compound regarding cell growth inhibition.
Nevertheless, it was verified that the concomitant use of the individual
compounds provided the strongest decrease in viable cell number. Overall,
evidence was found for alterations in cell cycle and apoptosis, involving p53 and
caspase-3. Furthermore, our data suggests that the phenolic acids identified in
the extract are at least partially responsible for the cytotoxicity induced by
this mushroom extract.
PMID- 26434320
TI - Pepsin-solubilised collagen (PSC) from Red Sea cucumber (Stichopus japonicus)
regulates cell cycle and the fibronectin synthesis in HaCaT cell migration.
AB - Pepsin-solubilised collagen (PSC) from Red Sea cucumber (Stichopus japonicus) was
studied with respect to its wound-healing effects on a human keratinocyte (HaCaT)
cell line. Disaggregated collagen fibres were treated with 0.1M NaOH for 24h and
digested with pepsin for 72h to reach maximum yield of 26.6%. The results of an
in vitro wound-healing test showed that migration of HaCaT cells was 1.5-fold
faster on PSC-coated plates than on untreated plates. The migration rate of sea
cucumber PSC was similar to that of rat PSC, but five times higher than that of
bovine gelatin. HaCaT cells grown on PSC-coated plates revealed increased
fibronectin synthesis (6-fold and 3-fold compared to gelatin and rat PSC,
respectively). Additionally, sea cucumber PSCs induced HaCaT cell proliferation
by decreasing the G1 phase by 5% and maintaining a larger population (8%) of
cells in mitosis. Collagen from Red Sea cucumber might be useful as an
alternative to mammalian collagen in the nutraceutical and pharmaceutical
industries.
PMID- 26434321
TI - Antioxidant, antifungal and antiviral activities of chitosan from the larvae of
housefly, Musca domestica L.
AB - Antioxidant activity of the chitosan from the larvae of Musca domestica L. was
evaluated in two different reactive oxygen species assays, and inhibitory effects
against seven fungi were also tested. The results showed that the chitosan had
scavenging activity for hydroxyl and superoxide radicals which were similar to
that of ascorbic acid. Also the chitosan exhibited excellent antifungal activity,
especially in the low concentration, it could significantly inhibit the growth of
Rhizopus stolonifer. Besides, antiviral results demonstrated that the chitosan
could effectively inhibit the infection of AcMNPV and BmNPV. These results
suggested that the chitosan from the larvae of housefly could be effectively used
as a natural antioxidant to protect the human body from free radicals and retard
the progress of many chronic diseases. Furthermore, the chitosan with antiviral
and antifungal activity might provide useful information for antiviral breeding
technology of economic insect and development of plant pathological control.
PMID- 26434322
TI - Differential partitioning of antioxidants, including hydroxytyrosol, in human
plasma and LDL: implications for their antioxidant activity in vivo.
AB - In vivo studies of LDL oxidation following consumption of natural phenolic
compounds have yielded mixed results. It is reported that the amphiphilic
hydroxytyrosol, after addition to human plasma, does not accumulate in LDL but
protects plasma lipids, which are extracted together with hydroxytyrosol, from
chemically-induced oxidation. Thus, a novel methodology was proposed, which does
not rely on LDL separation and subsequent oxidation but is based on the oxidation
of total lipids - simultaneously extracted from plasma with antioxidants - to
evaluate the effects of micronutrients that do not partition into LDL, after in
vivo supplementation.
PMID- 26434323
TI - Determination of nonylphenol ethoxylate metabolites in vegetables and crops by
high performance liquid chromatography-tandem mass spectrometry.
AB - A method has been developed for the simultaneous determination of the
concentration of nonylphenol (4-NP), nonylphenol monoethoxylates (NP1EO) and
nonylphenol diethoxylates (NP2EO) in vegetables and crops by liquid
chromatography-tandem quadrupole mass spectrometry (HPLC-MS/MS). These target
compounds were extracted from vegetable and crop samples with acetonitrile, and
then the extracts were cleaned using solid phase extraction with graphitised
carbon black tandem primary secondary amine (PSA) cartridges. The MS method
enabled highly reliable identification by monitoring the corresponding ammonium
adduct [M+NH4](+) in the positive mode for NP1EO and NP2EO, and the deprotonated
molecule [M-H](-) in the negative mode for 4-NP. Recoveries for the spiked
samples ranged from 65% to 118%. The limit of detection (LOD) of 4-NP, NP1EO and
NP2EO was 3, 5 and 0.1MUgkg(-1), respectively. This method would be useful for
the quick and routine detection of the residues of 4-NP, NP1EO and NP2EO in
vegetables and crops.
PMID- 26434324
TI - Ultra-performance liquid chromatographic separation of geometric isomers of
carotenoids and antioxidant activities of 20 tomato cultivars and breeding lines.
AB - All-trans-lutein, lycopene, beta-carotene and their 22 cis-isomers in 20 tomato
breeding were separated and identified by a rapid and sensitive UPLC method using
a 1.7MUm C18 column and a new gradient mobile phase based on methanol-MTBE-water
in 15 min. All-trans-carotenoids were predominant, but 9-cis, 13-cis-lutein, 5
cis, 9-cis, 13-cis, 15-cis, di-cis-lycopene, 9-cis, 13-cis, 15-cis and di-cis
beta-carotene were also found. The cis-isomers were identified using absorption
around 330nm and the Q-ratio. The total antioxidant activities as evaluated by
PCL and DPPH assays were found to correlate well with the total carotenoid
content, but not with the individual carotenoid or its different isomers. This
paper provides an efficient analytical method for obtaining a complete picture of
carotenoids in tomatoes. It can be a valuable tool for plant breeders, food
processors and researchers in developing designer tomatoes and tomato-products
with unique carotenoid compositions, and functional properties.
PMID- 26434325
TI - Utility of solid phase spectrophotometry for the modified determination of trace
amounts of cadmium in food samples.
AB - A modified selective, highly sensitive and accurate procedure for the
determination of trace amounts of cadmium which reacts with 1-(2
benzothiazolylazo)-2-hydroxy-3-naphthoic acid (BTAHNA) to give a deep violet
complex with high molar absorptivity (7.05*10(6)Lmol(-1) cm(-1), 3.92*10(7)Lmol(
1)cm(-1), 1.78*10(8)Lmol(-1)cm(-1), and 4.10*10(8)Lmol(-1)cm(-1)), fixed on a
Dowex 1-X8 type anion-exchange resin for 10mL, 100mL, 500mL, and 1000mL,
respectively. Calibration is linear over the range 0.2-3.5MUgL(-1) with RSD of
?1.14% (n=10). The detection and quantification limits were calculated.
Increasing the sample volume can enhance the sensitivity. The method has been
successfully applied for the determination of Cd(II) in food samples, water
samples and some salts samples without interfering effect of various cations and
anions.
PMID- 26434326
TI - Profiling of bioactive compounds in cultivars of Runner and Valencia peanut
market-types using liquid chromatography/APCI mass spectrometry.
AB - Peanuts are classified into four market-types (Runners, Spanish, Virginia and
Valencia). Studies on their phytochemical composition have focused mainly on
market-types other than Valencia. The objectives of this study are to evaluate
the phytochemical composition of cultivars of Valencia and Runner market-types.
Extracts of 25 peanut cultivars of Runner and Valencia market-types were analysed
using HPLC-DAD-MS analysis. Results showed major differences in UV profile of the
market-types. A major peak with m/z 317 identified as isorhamnetin was present
only in Valencia cultivars while its glycoside (isorhamnetin-3-O-rutinoside)
having m/z 625 was identified in both market-types. Genistein, daidzein, rutin,
quercetin and trans-resveratrol were also identified and quantified. Genistein
and daidzein concentrations (0.03mg/100g) were similar in both market-types.
trans-Resveratrol and rutin were significantly (p<0.05) higher in Runner
cultivars while quercetin was 10-fold higher (0.60+/-0.04mg/100g) in Valencia
cultivars making them a better source of this phytochemical.
PMID- 26434327
TI - Selective cloud point extraction for the determination of cadmium in food samples
by flame atomic absorption spectrometry.
AB - A new cloud point extraction (CPE) procedure for preconcentration of cadmium
prior to the determination by flame atomic absorption spectrometry (FAAS) was
developed. The method is based on the fact that cadmium could form hydrophobic
ion-associated complex in the presence of iodide and methyl green (MG), and the
hydrophobic ion-associated complex could be extracted into surfactant-rich phase.
The main factors affecting CPE procedure, such as pH, concentration of KI, MG and
surfactant, equilibrium temperature and incubation time, sample volume were
investigated. Potential interference from co-existing ions was largely eliminated
as most of co-existing ions can not form extractable ion-associated complex with
iodide and MG. Under the optimum conditions, the limit of detection (3sigma) and
limit of quantity (10sigma) were 0.90ngmL(-1) and 3.0ngmL(-1) for cadmium,
respectively, and relative standard deviation was 4.2% (c=50ngmL(-1), n=7). The
proposed method was successfully applied to determination of cadmium in the
certified reference rice sample (GBW08510) and food samples with satisfactory
results.
PMID- 26434328
TI - Simultaneous determination of eight underivatised biogenic amines in fish by
solid phase extraction and liquid chromatography-tandem mass spectrometry.
AB - Biogenic amines on fish tissue are formed as a result of bacterial contamination
and spoilage during storage. A new method based on liquid chromatography (LC) and
tandem mass spectrometry (MS/MS) using a triple quadrupole (QqQ) analyser was
developed for the analysis of eight biogenic amines (cadaverine, histamine,
phenylethylamine, putrescine, spermine, spermidine, tyramine and tryptamine) in
fish tissues. Sample preparation was performed by extraction with trichloroacetic
acid 5% and solid phase extraction clean up with STRATA X cartridge. The MS/MS
method was validated and compared with a method based on the analysis of dansyl
derivatives by LC and fluorescence detector (FD). MS/MS achieved higher
sensitivity (from 0.02mgkg(-1) for spermidine and phenylethylamine to 0.2mgkg(-1)
for spermine) when compared to FD (from 1mgkg(-1) for putrescine and tyramine to
4mgkg(-1) for histamine); MS/MS method showed higher precision too, with intraday
relative standard deviations (RSDs) from 1% to 4% with respect to those obtained
with FD method (from 3% to 17%). Recovery study was conducted at two different
fortification levels and the average ranged from 71% to 93% for all of the
studied compounds with RSDs lower than 18%. Matrix-matched standards were used to
counteract matrix effect observed in MS/MS determination. The applicability of
the method was demonstrated by the analysis of biogenic amines in fish obtained
from commercials of Valencia.
PMID- 26434329
TI - Rapid antioxidant capacity screening in herbal extracts using a simple flow
injection-spectrophotometric system.
AB - A simple flow injection (FI)-spectrophotometric system for the screening of
antioxidant capacity in herbal extracts was developed. The analysis was based on
the color disappearance due to the scavenging of 2,2-diphenyl-1-picrylhydrazyl
(DPPH) radical by antioxidant compounds. DPPH and ascorbic acid were used as
reagent and antioxidant standard, respectively. Effects of the DPPH
concentration, DPPH flow rate, and reaction coil length on sensitivity were
studied. The optimized condition provided the linear range of 0.010-0.300mM
ascorbic acid with less than 5%RSD(n=10). Detection limit and quantitation limit
were 0.004 and 0.013mM, respectively. Comparison of antioxidant capacity in some
herbal extracts determined by the FI system and a standard method was carried out
and no significant difference was obtained.
PMID- 26434330
TI - Investigation of antiradical activity of plant material by thin-layer
chromatography with image processing.
AB - A novel, easy, and cheap technique for preliminary quantitative evaluation of
antiradical activity, based on HPTLC, has been proposed. This method combines
chromatographic separation of polar compounds, present in plant extracts, with
data analysis by means of image processing software. Bleaching of the purple DPPH
colour, caused by substances with antiradical activity, was observed and recorded
using a photo camera. ImageJ, a free and open source image processing program was
used for quantitative measurements. For evaluation of assay efficiency, the
antiradical activity of rose flower extracts (from Rosa rugosa Thunb.) was
expressed as Standard Activity Coefficients (SACs), which are relative measures
of the activity to the four well known antioxidants; i.e., quercetin, gallic
acid, protocatechuic acid, and Trolox. The method uses small amounts of free
radical and is easily applicable - only a digital camera with freely available
open source software is required.
PMID- 26434331
TI - Comparison of chemical modifiers for direct determination of Cd, Cu and Zn in
food stuffs by solid-sampling-ETAAS.
AB - In this work, the capability of different chemical modifiers (Pd, Pd/Mg(NO3)2,
Pd/NH4NO3, NH4H2PO4, NH4H2PO4/Mg(NO3)2) to eliminate the matrix effects in the
direct determination of Cd, Cu and Zn in food-stuffs by solid sampling
electrothermal atomic absorption spectrometry was compared. The alternative
analytical lines were used for determination of Cu (327.4nm) and Zn (307.6nm) in
order to allow the introduction of reasonably high sample mass into the furnace.
Mixed modifiers containing palladium were useful to eliminate the matrix effect
in Cd determination. For Cu and Zn determination the application of Pd shows
satisfactory analytical performance. In the determinations of Cd and Zn the
phosphate containing modifiers shows elimination of matrix effects only when
applying them to a partially pyrolysed sample (at 400 degrees C). The achievable
limits of detection for Cd, Cu and Zn in solid samples were 0.279ngg(-1);
0.020MUgg(-1) and 2.04MUgg(-1), respectively.
PMID- 26434332
TI - Classification of 'Chemlali' accessions according to the geographical area using
chemometric methods of phenolic profiles analysed by HPLC-ESI-TOF-MS.
AB - The present work describes a classification method of Tunisian 'Chemlali' olive
oils based on their phenolic composition and geographical area. For this purpose,
the data obtained by HPLC-ESI-TOF-MS from 13 samples of extra virgin olive oils,
obtained from different production area throughout the country, were used for
this study focusing in 23 phenolics compounds detected. The quantitative results
showed a significant variability among the analysed oil samples. Factor analysis
method using principal component was applied to the data in order to reduce the
number of factors which explain the variability of the selected compounds. The
data matrix constructed was subjected to a canonical discriminant analysis (CDA)
in order to classify the oil samples. These results showed that 100% of cross
validated original group cases were correctly classified, which proves the
usefulness of the selected variables.
PMID- 26434333
TI - Feasibility study for producing a carrot/potato matrix reference material for 11
selected pesticides at EU MRL level: material processing, homogeneity and
stability assessment.
AB - The feasibility for producing a matrix reference material for selected pesticides
in a carrot/potato matrix was investigated. A commercially available baby food
(carrot/potato-based mash) was spiked with 11 pesticides at the respective EU
maximum residue limits (MRLs), and further processed by either freezing or freeze
drying. Batches of some 150 units were produced per material type. First, the
materials were assessed for the relative amount of pesticide recovered after
processing (ratio of pesticide concentration in the processed material to the
initially spiked pesticide concentration). In addition, the materials'
homogeneity (bottle-to-bottle variation), and the short-term (1 month) and mid
term (5 months) stability at different temperatures were assessed. For this, an
in-house validated GC-EI-MS method operated in the SIM mode with a sample
preparation procedure based on the QuEChERS ("quick, easy, cheap, effective,
rugged, and safe") principle was applied. Measurements on the frozen material
provided the most promising results (smallest analyte losses during production),
and also freeze-drying proved to be a suitable alternative processing technique
for most of the investigated pesticides. Both the frozen and the freeze-dried
material showed to be sufficiently homogeneous for the intended use, and storage
at -20 degrees C for 5 months did not reveal any detectable material degradation.
The results constitute an important step towards the development of a pesticide
matrix reference material.
PMID- 26434334
TI - Validation of a gas chromatography-electron capture detection of T-2 and HT-2
toxins in Chinese herbal medicines and related products after immunoaffinity
column clean-up and pre-column derivatization.
AB - A sensitive, reproducible and accurate gas chromatography-electron capture
detection (GC-ECD) method was developed for simultaneous determination of T-2 and
HT-2 toxins in Chinese herbal medicines (CHMs) and related products after
immunoaffinity column (IAC) clean-up and pre-column derivatization with N
heptafluoro-butyryl imidazole (HFBI). Then, gas chromatography-spectrometry
spectrometer (GC-MS) was applied to confirm the positive results and interfering
peaks. The limits of detection (LODs) for T-2 and HT-2 toxins were 1.88 and
0.47ng/g, and the recoveries for different CHMs ranged from 89.2% to 99.1% with
relative standard deviation (RSD) <6.0% for T-2 and from 85.9% to 99.0% with RSD
<8.8% for HT-2 toxin, respectively. The validated method was successfully applied
for the determination of T-2 and HT-2 toxins in 89 Chinese herbal medicines and
10 related products from various sources, where it was found that T-2 and HT-2
toxins were not detected in any of the tested samples. These results were
reliable by confirmation using GC-MS. Some unknown peaks were interfering peaks
not the target toxins.
PMID- 26434335
TI - Application of response surface methodology to optimise supercritical carbon
dioxide extraction of essential oil from Cyperus rotundus Linn.
AB - Supercritical fluid extraction with carbon dioxide (SC-CO2 extraction) was
performed to isolate essential oils from the rhizomes of Cyperus rotundus Linn.
Effects of temperature, pressure, extraction time, and CO2 flow rate on the yield
of essential oils were investigated by response surface methodology (RSM). The
oil yield was represented by a second-order polynomial model using central
composite rotatable design (CCRD). The oil yield increased significantly with
pressure (p<0.0001) and CO2 flow rate (p<0.01). The maximum oil yield from the
response surface equation was predicted to be 1.82% using an extraction
temperature of 37.6 degrees C, pressure of 294.4bar, extraction time of 119.8
min, and CO2 flow rate of 20.9L/h.
PMID- 26434336
TI - Elemental analysis of nutritional preparations by inductively coupled plasma mass
and optical emission spectrometry.
AB - This paper reports the development and using of ICP-MS and ICP-OES methods for
determination of major, minor and trace elements in multivitamin preparations and
dietary supplements and, based on results, their classification using
multivariate statistical methods. The method was optimised and evaluated with the
use of "in-house" reference material, commercial reference materials and spiked
samples. Macroelements (Na, K, Ca, Mg, P), microelements (Cu, Fe, Mn, Zn, Se,
Cr), toxic elements (As, Cd, Pb, Ni, V) and a whole series of other elements
(e.g. REEs, Ti, Au, Pt, Pd, etc.) were detected with excellent limits of
detection as well as other procedure parameters suitable for the purpose of the
elemental analysis. As for physiologically significant elements, contents were
found as follows (mgkg(-1)): Ca 560-196,000, Mg 308-70,300, Na 289-74,000, K from
undetectable to 28,200, Cu 28-1460, P from undetectable to 217,000, Zn 2.1
25,000, Fe 115-39,400, Mn 28-1860, Cr 0.486-26.6, Mo 0.0418-9.88, and Se 0.395
161. It was found out, if compared with recommended daily intakes, that maximally
50% Ca, 37% Mg, 3% K, 20% P, 14% Na, 100% Cu, 160% Mn, 190% Fe, 120% Zn, 24% Cr,
29% Mo and 79% Se can be obtained from one dose. Extreme samples presenting a
possible health risk (Ni content nearly 200mgkg(-1)) were indicated. Most of the
remaining elements (e.g. REEs) were analysed in order to get reference values for
nutritional preparation.
PMID- 26434337
TI - Chromium determination in food by slurry sampling graphite furnace atomic
absorption spectrometry using classical and permanent modifiers.
AB - A simple method, using permanent modifiers, has been developed for chromium (Cr)
determination in food of plant origin by the slurry sampling graphite furnace
atomic absorption spectrometry. In particular comparison of the action of
Mg(NO3)2, iridium (Ir)/niobium (Nb) and iridium (Ir)/tungsten (W) was examined.
Finally, for chromium determination in food, the mixture of 2MUg of Ir with 10MUg
of Nb was used as permanent modifier. The analytical procedure was optimised
carefully on the basis of the data from pyrolysis and atomisation temperature
curves studies. The results obtained for four certified reference materials using
external calibration with aqueous standards were in good agreement with the
certified values. The precision and accuracy of Cr determination by the described
method were also acceptable: the RSD were lower than 10% and recoveries for CRMs
were in the range of 95-103%. The characteristic mass for chromium was determined
to be 3.9pg and the detection limit for the optimised procedure at the 0.75%
(w/v) slurry concentration - 86.6ngg(-1).
PMID- 26434338
TI - Application of differential scanning calorimetry (DSC), HPLC and pNMR for
interpretation primary crystallisation caused by combined low and high melting
TAGs.
AB - The main goal of the present work was to assess the mechanism of crystallisation,
more precisely the dominant component responsible for primary crystal formations
and fat agglomerations. Therefore, DSC results exhibited significant effect on
temperature transition; peak sharpness and enthalpy at palm stearin (PS) levels
more than 40wt.%. HPLC data demonstrated slight reduction in the content of
POO/OPO at PS levels less than 40wt.%, while the excessive addition of PS more
than 40wt.% increased significantly PPO/POP content. The pNMR results showed
significant drop in SFC for blends containing PS less than 40wt.%, resulting in
low SFC less than 15% at body temperature (37 degrees C). Moreover, the values of
viscosity (eta) and shear stress (tau) at PS levels over 40wt.% expressed
excellent internal friction of the admixtures. All the data reported indicate
that PPO/POP was the major component of primary nucleus developed. In part, the
levels of PS should be less than 40wt.%, if these blends are designed to be used
for margarine production.
PMID- 26434339
TI - Rapid screening of phytosterols in orange juice by solid-phase microextraction on
polyacrylate fibre derivatisation and gas chromatographic-mass spectrometric.
AB - The potential of solid-phase microextraction on polyacrylate coated fibre, with
sequential or simultaneous trimethylsilyl derivatisation followed by gas
chromatographic-mass spectrometric analysis, was evaluated for a rapid
determination of the distribution of the phytosterols in aqueous food matrixes.
Influences of different parameters (bis(trimethylsilyl)trifluoro-acetamide and
sterol exposure time, sterol concentration and experimental protocol) on the
recovery of sterols were investigated to determine optimum conditions which were
tested for sterol extraction and analysis from orange juice. Best selectivity,
sterol recovery and derivatisation yields were obtained by extraction and
simultaneous derivatisation through immersion of the SPME-PA fibre in the orange
juice (10min, 65 degrees C) after headspace absorption of BSTFA (30min, 65
degrees C) on the fibre. Nevertheless the method developed cannot be used for
quantitative analysis. But the possibility to effect rapid screen of phytosterol
containing in complex media have been shown.
PMID- 26434340
TI - Preparative isolation and purification of xanthohumol from hops (Humulus lupulus
L.) by high-speed counter-current chromatography.
AB - Xanthohumol (XN) and related prenylflavonoids are the main bioactive components
of hops (Humulus lupulus L.). The current work is to investigate the use of high
speed counter-current chromatography (HSCCC) in search for high isolation of
xanthohumol from hops. A solvent system consisted of n-hexane-ethyl acetate
methanol-water at a volume ratio of 5:5:4:3 was employed. The results
demonstrated that the constructed method could be well applied for the isolation
of xanthohumol from hops extract. After HSCCC isolation procedure, the purity of
xanthohumol was over 95% assayed by HPLC and the yield of extraction was 93.60%.
The chemical structure identification of xanthohumol was carried out by UV, (1)H
NMR and (13)C NMR. The present results demonstrated that xanthohumol could be
efficiently obtained using a single HSCCC step from H. lupulus L. extract.
PMID- 26434341
TI - Flow injection spectrophotometry using natural reagent from Morinda citrifolia
root for determination of aluminium in tea.
AB - A flow injection (FI) spectrophotometric method with using natural reagent
extracted from Morinda citrifolia root has been developed for determination of
aluminium. The extract contained anthraquinone compounds which could react with
Al(3+) to form reddish complexes which had maximum absorption wavelength at
499.0nm. The extract could be used as a reagent in FI system without further
purification to obtain pure compound. A sensitive method for determination of
aluminium in concentration range of 0.1-1.0mgL(-1), with detection limit of
0.05mgL(-1) was achieved. Relative standard deviations of 1.2% and 1.7% were
obtained for the determination of 0.1 and 0.6mgL(-1) Al(3+) (n=11). Sample
throughput of 35h(-1) was achieved with the consumption of 3mL each of carrier
and reagent solutions per injection. The developed method was successfully
applied to tea samples, validated by the FAAS standard method. The method is
simple, fast, economical and could be classified as a greener analytical method.
PMID- 26434342
TI - Analysis of six fungicides and one acaricide in still and fortified wines using
solid-phase microextraction-gas chromatography/tandem mass spectrometry.
AB - A multiresidue gas chromatographic method for the determination of six fungicides
(captan, chlorthalonil, folpet, iprodione, procymidone and vinclozolin) and one
acaricide (dicofol) in still and fortified wines was developed. Solid-phase
microextraction (SPME) was chosen for the extraction of the compounds from the
studied matrices and tandem mass spectrometry (MS/MS) detection was used. The
extraction consists in a solvent free and automated procedure and the detection
is highly sensitive and selective. Good linearity was obtained with correlation
coefficients of regression (R(2))>0.99 for all the compounds. Satisfactory
results of repeatability and intermediate precision were obtained for most of the
analytes (RSD?20%). Recoveries from spiked wine ranged from 80.1% to 112.0%.
Limits of quantification (LOQs) were considerably below the proposed maximum
residue limits (MRLs) for these compounds in grapes and below the suggested
limits for wine (MRLs/10), with the exception of captan.
PMID- 26434343
TI - Simultaneous determination of Sunset yellow and Tartrazine in soft drinks using
gold nanoparticles carbon paste electrode.
AB - The monitoring of synthetic dyes in foods is very important due to their
potential harmfulness to human beings. Herein, a carbon-paste electrode (CPE)
that is chemically modified with gold nanoparticles (nAu) was fabricated and used
for the determination of Sunset yellow (SY) and Tartrazine (Tz). Cyclic and
differential pulse voltammetry (CV and DPV) results revealed two well-resolved
anodic peaks for SY and Tz with remarkably increase in oxidation signals of these
colourants. Based on this, a novel electrochemical method was developed for the
simultaneous determination of SY and Tz. High sensitivity and selectivity, sub
micromolar detection limit, high reproducibility and regeneration of the
electrode surface by simple polishing make the nAu-CPE electrode very suitable
for the determination of SY and Tz in commercially available soft drinks. The
detection limits was 3.0*10(-8) and 2.0*10(-9)moll(-1) for SY and Tz,
respectively, which are remarkably lower than those reported previously for SY
and Tz using other modified electrodes.
PMID- 26434345
TI - Molecularly imprinted solid-phase extraction coupled to liquid chromatography for
determination of Sudan dyes in preserved beancurds.
AB - New molecularly imprinted microspheres synthesized by suspension polymerisation
using phenylamine and naphthol as mimic template were successfully applied as
selective sorbents for the solid-phase extraction used for the simultaneous
determination of four Sudan dyes from preserved beancurd products. The obtained
imprinted microspheres showed good recognition and selectivity to the four Sudan
dyes in aqueous solution and the affinity could be easily controlled by adjusting
the property of the solution. Under the selected experimental condition, the
recoveries of the Sudan dyes in preserved beancurds at three spiked levels were
ranged between 90.2-104.5% with the relative standard deviation of less than
6.8%. The limit of detection (LOD) and limit of quantification (LOQ) based on a
signal-to-noise of 3 and 10 were in the range of 0.005-0.009MUgg(-1) and 0.015
0.030MUgg(-1), respectively. Comparing with alumina and C18-based extraction, the
selectivity and repeatability of molecularly imprinted solid-phase extraction
(MISPE) were obviously improved. This method could be potentially applied for the
determination of Sudan dyes in complicated food samples.
PMID- 26434344
TI - Detection of adulterated commercial Spanish beeswax.
AB - The physical and chemical parameters (melting point and saponification number),
and the fraction of hydrocarbons, monoesters, acids and alcohols have been
determined in 90 samples of Spanish commercial beeswax from Apis mellifera L. The
adulteration with paraffins of different melting point, cow tallow, stearic acid,
and carnauba wax were determined by HTGC-FID/MS detection, and the research was
focussed mainly on paraffins and microcrystallines waxes. In general, the added
adulterant can be identified by the presence of non-naturally beeswax components,
and by the differences of values of selected components between pure and
adulterated beeswax. The detection limits were determined using pure and
adulterated beeswax with different amounts of added waxes (5%, 10%, 20% and 30%).
Percentages higher than 1-5% of each adulterant can be detected in the mixtures.
Paraffin waxes were confirmed in 33 of the 90 samples analysed at concentrations
between 5% and 30%.
PMID- 26434346
TI - A proteomic approach to detect lactosylation and other chemical changes in stored
milk protein concentrate.
AB - Milk proteins undergo chemical changes such as lactosylation, deamidation and
protein cross-linking during processing and storage of milk products. A proteomic
technique combining two-dimensional gel electrophoresis and mass spectrometry was
used to investigate chemical modifications to proteins, in milk protein
concentrate (MPC80), during storage. Lactosylation, deamidation and protein cross
linking were observed on 2-DE gels. They were storage temperature-, humidity- and
time-dependent. Lactosylated whey proteins were well separated on 2-DE in
vertical stacks of spots. The masses of the spots varied by multiples of 324,
indicating the attachment of lactose to lysine residues in the proteins. The
trypsin-digested spots of alpha-lactalbumin were analysed by MALDI-TOF mass
spectrometry, which indicated multiple lactosylation sites. The lactose adducts
on gels were quantified by image analysis, allowing development of adducts over
time to be monitored. The results show that proteomics can be used for the
detection and quantification of chemical modifications to proteins in stored
MPC80.
PMID- 26434347
TI - Spectroscopic investigation on the interaction of 3,7-dihydroxyflavone with
different isomers of human serum albumin.
AB - The interaction mechanism of 3,7-dihydroxyflavone (3,7-diHF) and human serum
albumin (HSA) was investigated by fluorescence quenching, fluorescence
enhancement, steady-state and time-resolved fluorescence emission and UV-vis
absorption spectrometry. The binding site of 3,7-diHF on protein was determined
by investigating the spectroscopic properties of 3,7-diHF-HSA complex at pH 7.4
and pH 3.5 individually, and confirmed by the site marker competitive
experiments. The binding parameters of 3,7-diHF-HSA complex were estimated by
fluorescence quenching experiments, and the data were in good agreement with the
results obtained from fluorescence enhancement measurements. A remarkable
increase in the fluorescence anisotropy values suggested that 3,7-diHF bound at a
motional restricted pocket on HSA. The results indicated that 3,7-diHF, in
anionic form, was bound within the hydrophobic pockets of the subdomain IIA of
HSA (site I), and stabilised mainly by electrostatic force and ionic
interactions. The binding mode of drug-protein was discussed based on above
experimental results.
PMID- 26434348
TI - An improved method for thin layer chromatographic analysis of saponins.
AB - Analysis of saponins by thin layer chromatography (TLC) is reported. The solvent
system was n-butanol:water:acetic acid (84:14:7). Detection of saponins on the
TLC plates after development and air-drying was done by immersion in a suspension
of sheep erythrocytes, followed by washing off the excess blood on the plate
surface. Saponins appeared as white spots against a pink background. The protocol
provided specific detection of saponins in the saponins enriched extracts from
Aesculusindica (Wall. ex Camb.) Hook.f., Lonicera japonica Thunb., Silene inflata
Sm., Sapindusmukorossi Gaertn., Chlorophytum borivilianum Santapau & Fernandes,
Asparagusadscendens Roxb., Asparagus racemosus Willd., Agave americana L.,
Camellia sinensis [L.] O. Kuntze. The protocol is convenient, inexpensive, does
not require any corrosive chemicals and provides specific detection of saponins.
PMID- 26434351
TI - Shot Noise of Charge and Spin Current of a Quantum Dot Coupled to Semiconductor
Electrodes.
AB - On the basis of the scattering matrix theory and nonequilibrium green function
method, we have investigated the fluctuations of charge and spin current of the
systems that consist of a quantum dot (QD) with a resonant level coupled to two
semiconductor contacts within in alternative site (AS) and alternative bond (AB)
framework, where two transverse (Bx) and longitudinal (Bz) magnetic fields are
applied to the QD. It is only necessary to use the autocorrelation function to
characterize the fluctuations of charge current for a twoterminal system because
of the relation that is defined as Sigmaalpha e Salphabeta = Sigmabeta e
Salphabeta = 0. Our result shows that both auto-shot noise (SLL) and cross-shot
noise (SLR) are essential to characterize the fluctuations of spin current when
Bx is present. Moreover, our model calculations show that the sign of the cross
shot noise of spin current is negative for all surface states of AS/QD/AS
junctions, whereas it oscillates between positive and negative values for two
surface states of AB/QD/AB junctions as we sweep the gate voltage.
PMID- 26434352
TI - Equilibrium cluster fluids: pair interactions via inverse design.
AB - Inverse methods of statistical mechanics are becoming productive tools in the
design of materials with specific microstructures or properties. While initial
studies have focused on solid-state design targets (e.g., assembly of colloidal
superlattices), one can alternatively design fluid states with desired
morphologies. This work addresses the latter and demonstrates how a simple
iterative Boltzmann inversion strategy can be used to determine the isotropic
pair potential that reproduces the radial distribution function of a fluid of
amorphous clusters with prescribed size. The inverse designed pair potential of
this "ideal" cluster fluid, with its broad attractive well and narrow repulsive
barrier at larger separations, is qualitatively different from the so-called SALR
form most commonly associated with equilibrium cluster formation in colloids,
which features short-range attractive (SA) and long-range repulsive (LR)
contributions. These differences reflect alternative mechanisms for promoting
cluster formation with an isotropic pair potential, and they in turn produce
structured fluids with qualitatively different static and dynamic properties.
Specifically, equilibrium simulations show that the amorphous clusters resulting
from the inverse designed potentials display more uniformity in size and shape,
and they also show greater spatial and temporal resolution than those resulting
from SALR interactions.
PMID- 26434353
TI - Mapping the trajectory of the stria terminalis of the human limbic system using
high spatial resolution diffusion tensor tractography.
AB - The human limbic system is composed of gray and white matter structures which
have been known to have a role in core processes such as motivation, memory,
emotion, social behavior, self-awareness as well as certain primitive instincts.
Multiple functional studies investigated some of these brain tasks in human brain
limbic system. However, the underlying fine fiber pathways of the limbic system
including the trajectory of the stria terminalis have not been delineated
separately by prior diffusion weighted imaging. The ability to trace the
underlying fiber anatomy noninvasively using diffusion tensor tractography (DTT)
would be helpful to study the neurophysiology of these tracts in different
functions in future functional studies. Few studies have focused on the stria
terminalis using diffusion tensor tractography. Yet, the trajectory of the stria
terminalis and some fine subtrajectories of the fornix have not been elucidated
by prior DTT studies. We decided to further investigate these fine neuronal
trajectory using tractography and high spatial resolution diffusion tensor
imaging on 3T. Fifteen healthy right-handed men (age range 24-37 years) were
studied. We delineated the detailed trajectories of the stria terminalis and
fornix bilaterally in fifteen normal adult human brains. Using a high resolution
DTT technique, we demonstrate for the first time, the trajectory of stria
terminalis as well as detailed precommissural and postcommissural connectivity of
the forniceal columns.
PMID- 26434355
TI - Understanding death, extending life.
PMID- 26434354
TI - A molecular marker of disease activity in autoimmune liver diseases with
histopathological correlation; FoXp3/RORgammat ratio.
AB - Autoimmune liver diseases (AILDs) encompass a group of diseases with variable
clinicopathological manifestations. Th17 and Treg cells have roles in the
pathogenesis of AILDs with a balance shifted towards a relative increase in
activity of the Th17 cells. In this study, the balance between the transcription
factors of Treg and Th17 cells (FoXp3 and RORgammat) was sought as a molecular
marker of disease activity and to highlight the pathogenesis. The peripheral
blood samples of 46 treatment-naive patients were collected and RNA was
extracted. Real time PCR was performed and the ratio of gene expression was
calculated. Histopathology of 18 patients was obtained and the activity score of
these biopsies were also corroborated with their respective molecular
(FoXp3/RORgammat) (FRGT=FoXp3-ROR Gamma T) ratio. The FRGT ratio in healthy
individuals was close to 1 and in disease the ratio changed significantly. This
ratio (FRGT) was not significantly different in different varieties of AILD or in
adult or paediatric form of the disease. However, the ratio remained consistently
below 1 (mean 0.3) in acute disease and high (mean 224.7) in chronic or
asymptomatic form of the disease (p < 0.001). The histopathological activity
score also significantly correlated with the ratio. This signified the relative
excess of Th17 (RORgammat) in active disease as compared to Treg (FoXp3) and the
reverse in chronic form. This ratio can be an important peripheral molecular
marker to assess the disease activity without the necessity of performing a liver
biopsy.
PMID- 26434356
TI - BGA66 and BGA71 facilitate complement resistance of Borrelia bavariensis by
inhibiting assembly of the membrane attack complex.
AB - Borrelia (B.) bavariensis exhibits a marked tropism for nervous tissues and
frequently causes neurological manifestations in humans. The molecular mechanism
by which B. bavariensis overcomes innate immunity, in particular, complement
remains elusive. In contrast to other serum-resistant spirochetes, none of the B.
bavariensis isolates investigated bound complement regulators of the alternative
(AP) and classical pathway (CP) or proteolytically inactivated complement
components. Focusing on outer surface proteins BGA66 and BGA71, we demonstrated
that both molecules either inhibit AP, CP and terminal pathway (TP) activation,
or block activation of the CP and TP respectively. Both molecules bind complement
components C7, C8 and C9, and thereby prevent assembly of the terminal complement
complex. This inhibitory activity was confirmed by the introduction of the BGA66
and BGA71 encoding genes into a serum-sensitive B. garinii strain. Transformed
spirochetes producing either BGA66 or BGA71 overcome complement-mediated killing,
thus indicating that both proteins independently facilitate serum resistance of
B. bavariensis. The generation of C-terminally truncated proteins as well as a
chimeric BGA71 protein lead to the localization of the complement-interacting
binding site within the N-terminus. Collectively, our data reveal a novel immune
evasion strategy of B. bavariensis that is directed against the activation of the
TP.
PMID- 26434357
TI - Understanding the nutrition care needs of patients newly diagnosed with type 2
diabetes: a need for open communication and patient-focussed consultations.
AB - Patients who are newly diagnosed with type 2 diabetes mellitus (T2DM) commonly
attempt to modify their dietary intake after receiving nutrition care from
primary health professionals. Yet, adherence to dietary recommendations is rarely
sustained and factors influencing adherence are poorly understood. This study
explored T2DM patients' experiences of dietary change and their views on how
primary health professionals can best support long-term maintenance of dietary
change. A purposive sample of 10 individuals recently diagnosed with T2DM
participated in three individual semi-structured qualitative telephone
interviews: at baseline, then at 3 and 6 months after recruitment. Interview
questions were modified from the initial interview in order to investigate
emerging findings. A two-step data analysis process occurred through content
analysis of individual interviews and meta-synthesis of findings over time.
Participants initially made wide-ranging attempts to improve dietary behaviours,
but most experienced negative emotions from the restraint required to maintain a
healthy diet. Participants felt confused by the conflicting advice received from
health professionals and other sources such as friends, family, internet and
diabetes organisations. Participants frequently reported feeling rushed and not
heard in consultations, resulting in limited ongoing engagement with primary
healthcare services. These findings suggest that there is opportunity for primary
health professionals to enhance the dietary support provided to patients by:
acknowledging the challenges of sustained improvements in dietary intake; open
communication; and investing in patient relationships through more patient
focussed consultations.
PMID- 26434358
TI - Framework and optimisation procedure for flexible parametric survival models.
PMID- 26434359
TI - Reply to Letter to the Editor by Remontet et al.
PMID- 26434364
TI - Total Synthesis of Atisane-Type Diterpenoids: Application of Diels-Alder
Cycloadditions of Podocarpane-Type Unmasked ortho-Benzoquinones.
AB - Few examples of [4 + 2] cycloaddition with unmasked ortho-benzoquinones (UMOBs)
as carbodiene have been reported in complex molecule synthesis. Herein we report
that this cycloaddition with podocarpane-type UMOB was developed and applied to
construct fully functionalized bicyclo[2.2.2]octanes. Based on this methodology,
divergent total syntheses of atisane-type diterpenoids, including (+/-)
crotobarin, crotogoudin, atisane-3beta,16alpha-diol, and 16S,17-dihydroxy-atisan
3-one, were accomplished in 14, 14, 12, and 16 steps, respectively. Key elements
in these total syntheses include: (1) FeCl3-catalyzed cationic cascade
cyclization to construct podocarpane-type skeleton; (2) Mn(III)/Co(II)-catalyzed
radical hydroxylation of alkene with high regio-, diastereo-, and
chemoselectivities; (3) and a ketal-deprotection/lactone
opening/deprotonation/lactonization cascade. Additionally, the synthetic utility
of the fully functionalized bicyclo[2.2.2]octane framework was further elucidated
by applying ring distortion strategy to afford different skeleton-rearranged
natural product-like compounds.
PMID- 26434365
TI - Body mass index, diabetes and survival after diagnosis of endometrial cancer: A
report from the HUNT-Survey.
AB - OBJECTIVE: We studied the association of body mass index (BMI) and diabetes with
all-cause death and endometrial cancer-specific death among women with
endometrial cancer (EC). METHODS: Included were 337 women in the Health Surveys
in North-Trondelag, Norway who were followed from EC diagnosis to death or end of
follow-up, 30th June 2012. Risks of death associated with BMI and diabetes were
estimated as hazard ratios (HRs) with 95% confidence intervals (95% CI). The
risks of EC-specific death were estimated as sub-HRs, after adjustment for
competing causes of death. We also studied the risk of death associated with
diabetes in women with BMI<25kg/m(2) and in women with BMI>=25kg/m(2). RESULTS:
During the median follow-up time of 6.7years, 166 women (49.3%) died. Diabetes
increased the risk of all-cause death (HR 2.14, 95% CI: 1.26-3.63) and
endometrial cancer-specific death (SHR, 2.62, 95% CI: 1.07-6.43) after adjustment
for age, histological type and stage of EC. BMI was not associated with risk of
all-cause or EC-specific death. The increased risk of both all-cause death and EC
specific death in diabetic women seemed to be more pronounced in women with
BMI<25kg/m(2) (HR 6.35, 95% CI: 1.90-21.14) compared to women with BMI>25kg/m(2)
(HR 1.80, 95% CI: 0.98-3.33). CONCLUSIONS: Diabetes, but not BMI, was associated
with increased risk of all-cause death and death from EC. The increased risk of
death associated with diabetes seemed to be most pronounced in women with
BMI<25kg/m(2).
PMID- 26434366
TI - Magnetic ionic liquids as PCR-compatible solvents for DNA extraction from
biological samples.
AB - A polymerase chain reaction (PCR) buffer was systematically designed to relieve
the inhibition caused by hydrophobic magnetic ionic liquids (MILs). We describe a
simple, rapid method for MIL-based plasmid DNA extraction from crude bacterial
cell lysate in which DNA-enriched MIL is transferred directly to a PCR tube for
analysis.
PMID- 26434368
TI - Gingipain-dependent augmentation by Porphyromonas gingivalis of phagocytosis of
Tannerella forsythia.
AB - In the pathogenesis of periodontitis, Porphyromonas gingivalis plays a role as a
keystone pathogen that manipulates host immune responses leading to dysbiotic
oral microbial communities. Arg-gingipains (RgpA and RgpB) and Lys-gingipain
(Kgp) are responsible for the majority of bacterial proteolytic activity and play
essential roles in bacterial virulence. Therefore, gingipains are often
considered as therapeutic targets. This study investigated the role of gingipains
in the modulation by P. gingivalis of phagocytosis of Tannerella forsythia by
macrophages. Phagocytosis of T. forsythia was significantly enhanced by
coinfection with P. gingivalis in a multiplicity of infection-dependent and
gingipain-dependent manner. Mutation of either Kgp or Rgp in the coinfecting P.
gingivalis resulted in attenuated enhancement of T. forsythia phagocytosis.
Inhibition of coaggregation between the two bacterial species reduced
phagocytosis of T. forsythia in mixed infection, and this coaggregation was
dependent on gingipains. Inhibition of gingipain protease activities in
coinfecting P. gingivalis abated the coaggregation and the enhancement of T.
forsythia phagocytosis. However, the direct effect of protease activities of
gingipains on T. forsythia seemed to be minimal. Although most of the
phagocytosed T. forsythia were cleared in infected macrophages, more T. forsythia
remained in cells coinfected with gingipain-expressing P. gingivalis than in
cells coinfected with the gingipain-null mutant or infected only with T.
forsythia at 24 and 48 h post-infection. Collectively, these results suggest that
P. gingivalis, mainly via its gingipains, alters the clearance of T. forsythia,
and provide some insights into the role of P. gingivalis as a keystone pathogen.
PMID- 26434369
TI - Synthetic cannabinoid (K2) use in pediatric patients and cardiovascular events: A
place for pericarditis and myopericarditis?
PMID- 26434367
TI - Inflammation-associated alterations to the intestinal microbiota reduce
colonization resistance against non-typhoidal Salmonella during concurrent
malaria parasite infection.
AB - Childhood malaria is a risk factor for disseminated infections with non-typhoidal
Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered
cytokine environment have been implicated in increased susceptibility to NTS, it
is not known whether malaria affects resistance to intestinal colonization with
NTS. To address this question, we utilized a murine model of co-infection.
Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory
macrophages and T cells into the intestinal mucosa and increased expression of
inflammatory cytokines. These mucosal responses were also observed in germ-free
mice, showing that they are independent of the resident microbiota. Remarkably,
P. yoelii infection reduced colonization resistance of mice against S. enterica
serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal
microbiota revealed marked changes in the community structure. Shifts in the
microbiota increased susceptibility to intestinal colonization by S. Typhimurium,
as demonstrated by microbiota reconstitution of germ-free mice. These results
show that P. yoelii infection, via alterations to the microbial community in the
intestine, decreases resistance to intestinal colonization with NTS. Further they
raise the possibility that decreased colonization resistance may synergize with
effects of malaria on systemic immunity to increase susceptibility to
disseminated NTS infections.
PMID- 26434370
TI - Prostaglandin E2 Mediates Cardiorespiratory Disturbances during Infection in
Neonates.
AB - OBJECTIVE: To determine whether infection, with associated eicosanoid release, is
a main cause of respiratory disruption in neonates, by measuring levels of
prostaglandin E2 (PGE2) and its metabolite (PGEM) in cerebrospinal fluid (CSF).
STUDY DESIGN: Of 59 eligible infants, 25 preterm infants (mean gestational age,
28 +/- 0.5 weeks) and 22 full-term infants (mean gestational age, 40 +/- 0.5
weeks) from a level 3 neonatal intensive care unit and the general maternity
neonatal ward were enrolled prospectively. Infants with a condition that can
cause secondary apnea were excluded. Cardiorespiratory disturbances, such as
apnea, bradycardia, and desaturation (ABD) events, were quantified. All infants
were subjected to standard laboratory analysis of blood and CSF concentrations of
biomarkers, including PGE2 and PGEM, within 24 hours of lumbar puncture, which
were correlated with ABD events and culture-verified infections. RESULTS: PGEM
levels were highest in infants with culture-verified sepsis and meningitis (P <
.01). In infants without culture-verified bacterial infections, PGEM levels were
higher in preterm infants compared with term infants (P < .05). The numbers of
desaturation events and apnea events in neonates were positively associated with
PGE2 levels in CSF (P < .05). CONCLUSION: PGE2 and PGEM are rapidly elevated in
CSF during an infectious event and may explain cardiorespiratory disturbances,
which are the major presenting symptoms of neonatal infections. PGE2 and PGEM are
released during bacterial infections and could serve as biomarkers for sepsis and
autonomic dysfunction in neonates.
PMID- 26434371
TI - Reply: To PMID 26165442.
PMID- 26434372
TI - Screen-Based Behaviors of Children and Cardiovascular Risk Factors.
AB - OBJECTIVE: To determine whether the amount of time spent in screen-based
behaviors (SBBs; television viewing, computer use, and playing electronic games)
is independently associated with individual and clustered cardiovascular disease
(CVD) risk factors among elementary school children. STUDY DESIGN: Baseline data
were used from 264 children (age 7-10 years) participating in the Transform-Us!
cluster-randomized controlled trial. Time (h/d) spent in SBBs was obtained using
a parent proxy-report questionnaire. Anthropometrics, blood pressure (BP), and
lipids were measured using standard techniques. A clustered CVD risk score was
calculated as the average of the standardized values of the subcomponents (waist
circumference [WC], systolic BP, diastolic BP, and lipids). RESULTS: After
adjusting for sex, parent education, physical activity (accelerometry), diet, and
WC (when adiposity was not the outcome), television viewing time was positively
associated with body mass index z-score (P = .002), WC (P = .02), and systolic BP
(P = .05). Electronic games was positively associated with low density
lipoprotein levels (P = .05), and total screen-time was positively associated
with body mass index (P = .02). CONCLUSIONS: Differential associations were
observed between types of SBBs and CVD risk factors, indicating that not all SBBs
are adversely associated with obesity and CVD risk. There is a need to
differentiate between types of SBBs when evaluating the CVD risk associated with
screen behaviors in children. TRIAL REGISTRATION: International Standard
Randomized Controlled Trial: ISRCTN83725066; Australian New Zealand Clinical
Trials Registry: ACTRN12609000715279.
PMID- 26434373
TI - Temperature measurement in human fat with T2 imaging.
AB - PURPOSE: To develop a method for noninvasive T2 -based thermometry that enables
estimation of the in vivo temperature in adipose tissues at both 1.5T and 3T
field strengths. MATERIALS AND METHODS: A total of 27 apparent T2 -temperature
measurement sets were performed on 13 human abdominal adipose tissue samples
using an inversion prepared dual-echo single-slice sequence for apparent T2
estimation. The measurements were performed on Ingenia 1.5T and 3.0T scanners and
Achieva 1.5T and 3.0T scanners. The apparent T2 -values were measured at 4
degrees C temperature intervals during heating from 21 to 45 degrees C and
cooling to 21 degrees C. A two-parameter exponential fit was used to estimate the
apparent T2 to temperature dependency on a scanner-to-scanner basis. RESULTS: In
the temperature range evaluated (21-45 degrees C), the apparent T2 relaxation
times increased from an average of ~100 msec to 190 msec at 1.5T and an average
of ~130 msec to 220 msec at 3T. The measured T2 -relaxation times followed the
calibration curve with a median absolute error of 0.37 degrees C and maximum
error of 1.7 degrees C in 12 of the 13 samples, with the outlier having a notably
different appearance upon visual inspection prior to measurement. CONCLUSION:
Changes in apparent T2 relaxation time has the potential to be used for
accurately estimating local temperature within in vivo subcutaneous fat.
PMID- 26434375
TI - Fifth International Symposium on Childhood, Adolescent and Young Adult Non
Hodgkin Lymphoma Abstracts, 22 October 2015, Varese, Italy.
PMID- 26434374
TI - Health promotion and intellectual disability: listening to men.
AB - Taking responsibility for your own health has been a central tenet of public
health policy internationally for a number of decades. Governments in the UK and
internationally continue to promote a plethora of health promotion strategies,
encouraging individuals and communities to adopt healthy lifestyle choices.
Although it is widely recognised that men are not as proactive in seeking out
medical help or taking on health promotion advice as women, limited gender
sensitive research exists in the field of intellectual disability. Despite many
health promotion policy and practice strategies targeted at this population,
little research exists exploring whether men with intellectual disability
acknowledge health promotion advice. The study aimed to explore how men with mild
to-moderate intellectual disability understood and perceived their health and
what health promotion messages they acted upon. The study was based on a
participatory approach which enabled 11 men with intellectual disability to
contribute as steering group members and as participants through one-to-one
interviews. Data were collected between September 2011 and July 2012. Thematic
analysis was undertaken. The participants demonstrated a capacity to understand
their own health. This was inclusive of a concern about associating being obese
with being unhealthy. The participants reported good relationships with their
general practitioners (GPs) and felt valued, in particular when the GP was
prepared to offer specific intellectual disability and health promotion advice.
More gendered research inclusive of the views of this male population is required
and the study reiterates the importance of promoting the health of men and women
with intellectual disability.
PMID- 26434376
TI - Conformational analysis of an acyclic tetrapeptide: ab-initio structure
determination from X-ray powder diffraction, Hirshfeld surface analysis and
electronic structure.
AB - A terminally protected acyclic tetrapeptide has been synthesized, and the crystal
structure of its hydrated form, Boc-Tyr-Aib-Tyr-Ile-OMe.2H2O (1), has been
determined directly from powder X-ray diffraction data. The backbone conformation
of tetrapeptide (1) exhibiting two consecutive beta-turns is stabilized by two 4
> 1 intramolecular N-H . . . O hydrogen bonds. In the crystalline state, the
tetrapeptide molecules are assembled through water-mediated O-H . . . O hydrogen
bonds to form two-dimensional molecular sheets, which are further linked by
intermolecular C-H . . . O hydrogen bonds into a three-dimensional supramolecular
framework. The molecular electrostatic potential (MEP) surface of (1) has been
used to supplement the crystallographic observations. The nature of
intermolecular interactions in (1) has been analyzed quantitatively through the
Hirshfeld surface and two-dimensional fingerprint plot. The DFT optimized
molecular geometry of (1) agrees closely with that obtained from the X-ray
structure analysis. The present structure analysis of Boc-Tyr-Aib-Tyr-Ile-OMe.2H2
O (1) represents a case where ab-initio crystal structure of an acyclic
tetrapeptide with considerable molecular flexibility has been accomplished from
laboratory X-ray powder diffraction data.
PMID- 26434377
TI - Irradiated Graphene Loaded with SnO2 Quantum Dots for Energy Storage.
AB - Tin dioxide (SnO2) and graphene are unique strategic functional materials with
widespread technological applications, particularly in the areas of solar
batteries, optoelectronic devices, and solid-state gas sensors owing to advances
in optical and electronic properties. Versatile strategies for microstructural
evolution and related performance of SnO2 and graphene composites are of
fundamental importance in the development of electrode materials. Here we report
that a novel composite, SnO2 quantum dots (QDs) supported by graphene nanosheets
(GNSs), has been prepared successfully by a simple hydrothermal method and
electron-beam irradiation (EBI) strategies. Microstructure analysis indicates
that the EBI technique can induce the exfoliation of GNSs and increase their
interlayer spacing, resulting in the increase of GNS amorphization, disorder, and
defects and the removal of partial oxygen-containing functional groups on the
surface of GNSs. The investigation of SnO2 nanoparticles supported by GNSs
(SnO2/GNSs) reveals that the GNSs are loaded with SnO2 QDs, which are dispersed
uniformly on both sides of GNSs. Interestingly, the electrochemical performance
of SnO2/GNSs indicates that SnO2 QDs supported by a 210 kGy irradiated GNS shows
excellent cycle response, high specific capacity, and high reversible capacity.
This novel SnO2/GNS composite has potential practical applications in SnO2
electrode materials during Li(+) insertion/extraction.
PMID- 26434378
TI - Prognostic Value of Ambulatory Blood Pressure Monitoring in Obese Patients.
PMID- 26434379
TI - Systematic differences in time of cerebellar-neuron origin derived from
bromodeoxyuridine immunoperoxidase staining protocols and tritiated thymidine
autoradiography: A comparative study.
AB - As exogenous markers of DNA synthesis, 5-bromo-2'-deoxyuridine (BrdU) and
tritiated thymidine ([(3)H]TdR) have revolutionized our ability to identify
proliferating neuroblasts and follow their fate during the development of the
central nervous system. The effect of the incorporation of these molecules into
DNA on cell proliferation, migration and differentiation is frequently neglected
(Duque and Rakic, 2011. J. Neurosci. 31, 15205-15217). By a progressively delayed
cumulative labeling method, the current paper analyzes the development of the
cerebellum in mice exposed to either BrdU or [(3)H]TdR as embryos and collected
at postnatal day 90. We observed that, in comparison to the saline group, several
parameters of the cerebellum such as length of the cerebellar cortex, the area of
the molecular layer, Purkinje cell (PCs) number, the areas of the cerebellar
nuclei, and the number of the deep cerebellar nuclei (DCN) neurons were lower in
the BrdU injected group. No consequence of [(3)H]TdR administration was observed.
On the other hand, we also studied whether immunohistochemical methods, including
BrdU antibodies from different vendors (Sigma and Dako), partial DNA denaturation
procedures and trypsin pretreatments, alter the neurogenetic timetables of PC and
DCN neurons that resulted from analysis of these tissue specimens. Our analysis
revealed that the generative programs of these macroneurons were unrelated to
differences in the sensibility of BrdU antibodies but were dependent on the
partial denaturation of DNA and trypsin digestion protocols. Finally, we also
compare the generation and spatial distribution of PC and DCN neurons in mice
exposed to either BrdU or [(3)H]TdR to assess whether the results obtained by
these two markers are quantitatively similar. The data presented here show that
systematic differences exist in the pattern of neurogenesis and the spatial
location of cerebellar neurons between mice injected with BrdU or [(3)H]TdR.
These findings have implications for the interpretation of results obtained by
both exogenous makers as an index of the production, migration and settling of
neurons in the developing central nervous system.
PMID- 26434380
TI - Invasive pneumococcal disease among children younger than 5 years of age before
and after introduction of pneumococcal conjugate vaccine in Casablanca, Morocco.
AB - OBJECTIVES: The purpose of this study was to compare the incidence rate of
invasive pneumococcal disease, the rates of antibiotic resistance and serotype
distribution among children <=5 years old before and after PCVs introduction in
Casablanca, Morocco. METHODS: This study was conducted at the Ibn Rochd
University Hospital Centre of Casablanca during two periods encompassing pre-and
post-implementation of PCVs, respectively from January 2007 to October 2010 and
from January 2011 to December 2014. All the non-duplicate invasive S. pneumoniae
isolates recovered during the study periods were included. RESULTS: There were
136 cases of IPD, 91 before and 45 after PCVs introduction. The greatest decrease
in incidence rate of IPD occurred in children <= 2 years of age declining from
34.6 to 13.5 per 100,000 populations (p<0.0001) before and after vaccination,
respectively. The incidence rate of PCV-7, PCV-10 non-PCV-7 and PCV-13 non-PCV-10
serotypes decrease significantly from 18.0 to 4.6, from 5.7 to 1.3 and from 5.7
to 0.8/100,000 population (p<0.001) in the same age, respectively. CONCLUSION:
Shifts in the distribution of IPD serotypes and reductions in the incidence rate
of disease suggest an effective reduction of the burden of IPD in children, but
continued high quality surveillance is critical to assess the changes in serotype
distributions.
PMID- 26434381
TI - Nutrition for homeless populations: shelters and soup kitchens as opportunities
for intervention.
AB - Nutrition is a daily challenge for the homeless population in America. Homeless
individuals suffer from a high prevalence of diseases related to poor diet, yet
there has been little public health effort to improve nutrition in this
population. Shelters and soup kitchens may have an untapped potential to impact
food access, choice and quality. We offer ideas for intervention and lessons
learned from ten shelters and soup kitchens around Greater Boston, MA, USA. By
advancing food quality, education and policies in shelters and soup kitchens, the
homeless population can be given an opportunity to restore its nutrition and
health.
PMID- 26434382
TI - Randomized, controlled, double-blind trial of topical lidocaine gel and
intrauterine lidocaine infusion for pain relief during saline contrast
sonohysterography.
AB - OBJECTIVES: To evaluate the efficacy of topical lidocaine gel and intrauterine
lidocaine infusion administered prior to saline contrast sonohysterography (SCSH)
in reducing pain level during the procedure. METHODS: This was a randomized,
double-blind, placebo controlled trial. We recruited 120 women scheduled to
undergo SCSH and randomized them into one of three groups according to
administration of gel and intrauterine infusion immediately prior to the
procedure: (1) the 'lidocaine gel' group received 3 mL 2% lidocaine gel applied
to the cervix and intrauterine infusion, using an infant feeding tube without
balloon, of 5 mL normal saline; (2) the 'lidocaine infusion' group received 3 mL
gel lubricant applied to the cervix and intrauterine infusion of 5 mL 2%
lidocaine; (3) the placebo group received 3 mL gel lubricant applied to the
cervix and intrauterine infusion of 5 mL normal saline. The tube was left in
place for the SCSH procedure. The primary outcome measure was the overall pain
level (on a scale of 0-100) reported by the women during the SCSH procedure.
Women also rated their pain levels at various other time points and an observer
assessed visible signs of the women's discomfort during the procedure, producing
a distress score. RESULTS: There were no significant differences among the three
groups in baseline characteristics, volume of saline solution infused, tenaculum
use and duration and difficulty level of the SCSH procedure. The median (range)
pain scores during normal saline infusion for the SCSH procedure were 0 (0-65) in
the placebo group, 2.5 (0-80) in the lidocaine gel group, and 0 (0-70) in the
lidocaine infusion group. The pain scores at other time points, the overall pain
score and the distress score were also comparable for the three groups. No
significant adverse events were reported. CONCLUSIONS: SCSH performed with an
infant feeding tube without balloon is associated with very low pain levels.
Topical lidocaine gel application and intrauterine lidocaine infusion do not
further reduce pain levels during SCSH.
PMID- 26434385
TI - Tropical Medicine & International Health.
PMID- 26434383
TI - Magnetic bead fluorescent immunoassay for the rapid detection of the novel
inflammation marker YKL40 at the point-of-care.
AB - Pneumonia is one of the leading causes of death worldwide.We present a magnetic
bead fluorescent sandwich immunoassay that allows rapid serum measurement of the
novel inflammation marker YKL40 (CHI3L1) at the point of care (POC) that could
aid pneumonia diagnosis. The magnetic beads serve as the solid phase for
separation of YKL40 from serum. The readout is performed using a small and robust
fluorescence reader,which detects the turnover of a fluorescent substrate. The
assay procedure, from sample addition to data retrieval, consists of three steps
and is performed in less than 20 min. The presented assay has a linear range from
3 to 111 ng/mL, with a limit of detection of 2.9 ng/mL. The average recoveries
were found between 101 and 111%. The developed method was applied in sera from
healthy subjects (n= 14; c(YKL40)= 50 +/- 49 ng/mL) and from pneumonia patients
(n = 14; c(YKL40) = 333.6 +/- 225 ng/mL). The elevated YKL40 concentrations in
pneumonia-diseased patients are in good agreement with previously published data.
The POC-ready device provides a simple immunoassay that could help to optimize
pneumonia inflammation diagnostics in low-resource settings.
PMID- 26434386
TI - Redesign of a Fluorogenic Labeling System To Improve Surface Charge, Brightness,
and Binding Kinetics for Imaging the Functional Localization of Bromodomains.
AB - Protein labeling with fluorogenic probes is a powerful method for the imaging of
cellular proteins. The labeling time and fluorescence contrast of the fluorogenic
probes are critical factors for the precise spatiotemporal imaging of protein
dynamics in living cells. To address these issues, we took mutational and
chemical approaches to increase the labeling kinetics and fluorescence intensity
of fluorogenic PYP-tag probes. Because of charge-reversal mutations in PYP-tag
and probe redesign, the labeling reaction was accelerated by a factor of 18 in
vitro, and intracellular proteins were detected with an incubation period of only
1 min. The brightness of the probe both in vitro and in living cells was enhanced
by the mutant tag. Furthermore, we applied this system to the imaging analysis of
bromodomains. The labeled mutant tag successfully detected the localization of
bromodomains to acetylhistone and the disruption of the bromodomain-acetylhistone
interaction by a bromodomain inhibitor.
PMID- 26434384
TI - Immunodominant epitope-specific Th1 but not Th17 responses mediate protection
against Helicobacter pylori infection following UreB vaccination of BALB/c mice.
AB - Helicobacter pylori (H. pylori) infects more than half of the world's population,
causing chronic gastritis, peptic ulcers and gastric cancer. Urease B subunit
(UreB), a conserved protein of H. pylori, is capable of inducing specific CD4(+)
T-cell responses and provides protection against this infection. Previous studies
have confirmed the effectiveness of rUreB subunit vaccines in generating CD4(+) T
cell-mediated protection, but less is known regarding the roles of different
subtypes of T-cell immunity, such as Th1, Th2 and Th17, particularly the
immunodominant epitopes inducing specific CD4(+) T-cell responses, in vaccine
mediated protection. In this study, we demonstrated that the vaccination of
BALB/c mice with rUreB resulted in significant antigen-specific Th1 and Th17
immune responses. Importantly, two novel Th epitopes, UreB317-329 and UreB409
421, which are recognized by a major population of CD4(+) T cells, were
identified in immunized mice. Our results demonstrated that two novel epitopes
can simultaneously induce Th1 and Th17 immune responses; however, only the
epitope vaccine-induced CD4(+) T-cells secreting IFN-gamma mediated the
protection against H. pylori; cells secreting IL-17A did not. Taken together, our
results suggest that two novel immunodominant epitopes can induce Th1 and Th17
immune responses, but only the induced Th1 lymphocytes mediate protection against
H. pylori.
PMID- 26434387
TI - Smart gating membranes with in situ self-assembled responsive nanogels as
functional gates.
AB - Smart gating membranes, inspired by the gating function of ion channels across
cell membranes, are artificial membranes composed of non-responsive porous
membrane substrates and responsive gates in the membrane pores that are able to
dramatically regulate the trans-membrane transport of substances in response to
environmental stimuli. Easy fabrication, high flux, significant response and
strong mechanical strength are critical for the versatility of such smart gating
membranes. Here we show a novel and simple strategy for one-step fabrication of
smart gating membranes with three-dimensionally interconnected networks of
functional gates, by self-assembling responsive nanogels on membrane pore
surfaces in situ during a vapor-induced phase separation process for membrane
formation. The smart gating membranes with in situ self-assembled responsive
nanogels as functional gates show large flux, significant response and excellent
mechanical property simultaneously. Because of the easy fabrication method as
well as the concurrent enhancement of flux, response and mechanical property, the
proposed smart gating membranes will expand the scope of membrane applications,
and provide ever better performances in their applications.
PMID- 26434388
TI - Can we beat the biotin-avidin pair?: cucurbit[7]uril-based ultrahigh affinity
host-guest complexes and their applications.
AB - The design of synthetic, monovalent host-guest molecular recognition pairs is
still challenging and of particular interest to inquire into the limits of the
affinity that can be achieved with designed systems. In this regard,
cucurbit[7]uril (CB[7]), an important member of the host family cucurbit[n]uril
(CB[n], n = 5-8, 10, 14), has attracted much attention because of its ability to
form ultra-stable complexes with multiple guests. The strong hydrophobic effect
between the host cavity and guests, ion-dipole and dipole-dipole interactions of
guests with CB portals helps in cooperative and multiple noncovalent interactions
that are essential for realizing such strong complexations. These highly
selective, strong yet dynamic interactions can be exploited in many applications
including affinity chromatography, biomolecule immobilization, protein isolation,
biological catalysis, and sensor technologies. In this review, we summarize the
progress in the development of high affinity guests for CB[7], factors affecting
the stability of complexes, theoretical insights, and the utility of these high
affinity pairs in different challenging applications.
PMID- 26434389
TI - Terminal hepatic venule injury in liver biopsies of allogeneic haematopoietic
stem cell recipients-a study of 63 cases.
AB - AIMS: Subtle lesions of terminal hepatic venules (THVs) may be overlooked in
liver biopsies from haematopoietic stem cell transplant (HSCT) receipients when
graft-versus-host disease is the clinical concern. The aim of this study was to
evaluate the frequency of THV injury resembling sinusoidal obstruction syndrome
(SOS). METHODS AND RESULTS: Sixty-three consecutive biopsies from allogeneic HSCT
recipients were scored for injured THVs. Forty-nine (78%) biopsies had injured
THVs, and 10 (16%) were diagnosed with SOS (mean +/- standard deviation of
injured THVs/biopsy: 90 +/- 9%). Biopsies diagnosed with other diseases also had
injured THVs (36 +/- 33%). Biopsies from patients with cyclophosphamide plus
fractionated total body irradiation conditioning and biopsies taken within 100
days post-HSCT had significantly more occluded THVs (respectively: 40 +/- 38%, P
= 0.0188; and 35 +/- 35%, P = 0.0076) than those with other conditioning regimens
or in biopsies taken >100 days post-HSCT. All biopsies taken at any time in the 6
year post-HSCT period had similar amounts of THV phlebosclerosis (23 +/- 25%).
CONCLUSIONS: Our results demonstrate a high incidence of THV injuries resembling
SOS in post-HSCT liver biopsies. THV injuries were detectable for several years
post-HSCT, and were concurrent with other diagnoses. Our results also suggest
that SOS may be underdiagnosed.
PMID- 26434390
TI - Isolation and crystal structure of a dithiophene dication: controlling covalent
connection and disconnection with temperature and phase.
AB - A dithienylethene (1o) undergoes a two-electron chemical oxidation to a singlet
diradical as an open-isomer (1o(2+)) in solution, which cyclizes to a closed-form
(1c(2+)) upon cooling. The latter crystallizes out and its structure is analyzed
by single crystal X-ray diffraction. Equilibrium between 1o(2+) and 1c(2+) in
solution is observed by NMR and UV spectroscopy at various temperatures and is
further supported by reduction reactions with Zn powder.
PMID- 26434391
TI - Case of auricular herpes zoster associated with contralateral facial paralysis.
PMID- 26434392
TI - Protein function annotation using protein domain family resources.
AB - As a result of the genome sequencing and structural genomics initiatives, we have
a wealth of protein sequence and structural data. However, only about 1% of these
proteins have experimental functional annotations. As a result, computational
approaches that can predict protein functions are essential in bridging this
widening annotation gap. This article reviews the current approaches of protein
function prediction using structure and sequence based classification of protein
domain family resources with a special focus on functional families in the CATH
Gene3D resource.
PMID- 26434393
TI - Early-life characteristics and educational disparities in smoking.
AB - Health inequalities pose an important public health challenge in European
countries, for which increased social mobility has been suggested as a cause. We
sought to describe how the relationship between health inequalities and social
mobility varies among welfare regime types in the European region. Data from six
rounds of the European Social Survey was analyzed using multilevel statistical
techniques,stratified by welfare regime type, including 237,535 individuals from
136 countries. Social mobility among individuals was defined according to the
discrepancy between parental and offspring educational attainment. For each
welfare regime type, the association between social mobility and self-rated
health was examined using odds ratios and risk differences, controlling for
parental education. Upwardly mobile individuals had between 23 and 44% lower odds
of reporting bad or very bad self-rated health when compared to those who
remained stable. On an absolute scale, former USSR countries showed the biggest
and only significant differences for upward movement,while Scandinavian countries
showed the smallest. Downward social mobility tended to be associated with worse
health, but the results were less consistent. Upward social mobility is
associated with better health in all European welfare regime types. However, in
Scandinavian countries the association of upward mobility was smaller, suggesting
that the Nordic model is more effective in mitigating the impact of social
mobility on health and/or of health on mobility [corrected].
PMID- 26434394
TI - Global investigation of potential energy surfaces for the pyrolysis of C(1)-C(3)
hydrocarbons: toward the development of detailed kinetic models from first
principles.
AB - Detailed kinetic models (DKMs) are the most fundamental "bottom-up" approaches to
computational investigation of the pyrolysis and oxidation of fuels. The weakest
points of existing DKMs are incomplete information about the reaction types that
can be involved in the potential energy surfaces (PESs) in pyrolysis and
oxidation processes. Also, the computational thermodynamic parameters available
in the literature vary widely with the level of theory employed. More
sophisticated models require improvement both in our knowledge of the type of the
reactions involved and the consistency of thermodynamic and kinetic parameters.
In this paper, we aim to address these issues by developing ab initio models that
can be used to describe early stages of pyrolysis of C1-C3 hydrocarbons. We
applied a recently developed global reaction route mapping (GRRM) strategy to
systematically investigate the PES of the pyrolysis of C1-C3 hydrocarbons at a
consistent level of theory. The reactions are classified into 14 reaction types.
The critical points on the PES for all reactions in the network are calculated at
the highly accurate UCCSD(T)-F12b/cc-pVTZ//UM06-2X/cc-pVTZ level of theory. The
data reported in this paper can be used for first principle calculations of
kinetic constants and for a subsequent study on modeling the evolution of the
species from the reaction network of the pyrolysis and oxidation of C1-C3
hydrocarbons.
PMID- 26434395
TI - Thrombophilic genetic risk factors for liver fibrosis: To screen or not to
screen?
PMID- 26434396
TI - MRP2 in cholestasis: Putting down the anchor.
PMID- 26434397
TI - An evaluation of physician predictions of discharge on a general medicine
service.
AB - The goal of this study was to evaluate general medicine physicians' ability to
predict hospital discharge. We prospectively asked study subjects to predict
whether each patient under their care would be discharged on the next day, on the
same day, or neither. Discharge predictions were recorded at 3 time points:
mornings (7-9 am), midday (12-2 pm), or afternoons (5-7 pm), for a total of 2641
predictions. For predictions of next-day discharge, the sensitivity (SN) and
positive predictive value (PPV) were lowest in the morning (27% and 33%,
respectively), but increased by the afternoon (SN 67%, PPV 69%). Similarly, for
same-day discharge predictions, SN and PPV were highest at midday (88% and 79%,
respectively). We found that although physicians have difficulty predicting next
day discharges in the morning prior to the day of expected discharge, their
ability to correctly predict discharges continually improved as the time to
actual discharge decreased. Journal of Hospital Medicine 2015;10:808-810. (c)
2015 Society of Hospital Medicine.
PMID- 26434398
TI - Childhood-onset epilepsy five decades later. A prospective population-based
cohort study.
AB - OBJECTIVE: To study the impact of childhood-onset epilepsy on a variety of
outcomes across the life span. METHODS: A population-based cohort of 245 subjects
with childhood-onset epilepsy was assessed for outcomes at 45 years. In addition,
51 of 78 surviving subjects with uncomplicated epilepsy and 52 of 99 originally
matched controls participated in a detailed evaluation including
electroencephalography (EEG), imaging, and laboratory studies at 50 years.
RESULTS: Of 179 surviving subjects, 61% were in terminal 10-year remission and
43% in remission off medications. At 45 years, 95% of the idiopathic group, 72%
of the cryptogenic group, and 47% of the remote symptomatic group were in
terminal remission (p < 0.001). Abnormal neurologic signs were significantly more
common in subjects with uncomplicated epilepsy than in controls. Mortality during
period 1992-2012 was higher in subjects than in controls (9% vs. 1%, p = 0.02).
The rate of 3T MRI abnormalities was higher in subjects than in controls (risk
ratio [RR] 2.0; 1.3-3.1) specifically including findings considered markers of
cerebrovascular disease (RR 2.5; 1.04-5.9). Even subjects with idiopathic
epilepsy had higher rates of imaging abnormalities than controls (73% vs. 34%, p
= 0.002). SIGNIFICANCE: Long-term seizure outcomes are excellent and a function
of etiology. The presence of imaging abnormalities suggestive of vascular disease
may put these subjects at higher risk for clinically evident stroke and cognitive
changes as they age.
PMID- 26434399
TI - Recent advances in amino acid analysis by capillary electromigration methods,
2013-2015.
AB - We describe the most important research articles published on amino acid analysis
using CE during the period from June 2013 to May 2015, and follows the format of
the previous articles published in electrophoresis the new developments in amino
acid analysis with CE are mainly describing improvements in detection means and
injection methods. Enantiomeric separation developments are still important.
Focusing the applications, we describe the neurochemical and clinical works, but
also the metabolomic studies for which the publication number increase greatly.
Finally, works focused on amino acids in food and agricultural applications are
described.
PMID- 26434400
TI - A path to practical Solar Pumped Lasers via Radiative Energy Transfer.
AB - The optical conversion of incoherent solar radiation into a bright, coherent
laser beam enables the application of nonlinear optics to solar energy conversion
and storage. Here, we present an architecture for solar pumped lasers that uses a
luminescent solar concentrator to decouple the conventional trade-off between
solar absorption efficiency and the mode volume of the optical gain material. We
report a 750-MUm-thick Nd(3+)-doped YAG planar waveguide sensitized by a
luminescent CdSe/CdZnS (core/shell) colloidal nanocrystal, yielding a peak
cascade energy transfer of 14%, a broad spectral response in the visible portion
of the solar spectrum, and an equivalent quasi-CW solar lasing threshold of 23 W
cm(-2), or approximately 230 suns. The efficient coupling of incoherent,
spectrally broad sunlight in small gain volumes should allow the generation of
coherent laser light from intensities of less than 100 suns.
PMID- 26434401
TI - Hypertension: PATHWAY to improving the treatment of drug-resistant hypertension.
PMID- 26434403
TI - Infection: Efficacy of chlorhexidine against catheter-related infections.
PMID- 26434404
TI - Effect of high-dose atorvastatin on the cardiovascular risk associated with
individual components of metabolic syndrome: a subanalysis of the Treating to New
Targets (TNT) study.
AB - AIMS: To investigate the impact of intensive lipid-lowering with high-dose
atorvastatin on the cardiovascular risk associated with individual metabolic
syndrome components [high body mass index (BMI), elevated triglycerides, low high
density lipoprotein (HDL) cholesterol, hypertension and elevated fasting glucose]
in patients with coronary heart disease (CHD). METHODS: Patients with clinically
evident, stable CHD and low-density lipoprotein (LDL) cholesterol <3.4 mmol/l
(130 mg/dl) were randomized to double-blind therapy with atorvastatin 10 mg/day
(n = 5006) or 80 mg/day (n = 4995) after an 8-week open-label run-in with
atorvastatin 10 mg. The median follow-up was 4.9 years. The impact of individual
metabolic syndrome risk factors was tested on the primary endpoint, which was the
occurrence of a first major cardiovascular event. RESULTS: On-treatment LDL
cholesterol was 2.6 mmol/l (101 mg/dl) with atorvastatin 10 mg and 2.0 mmol/l (77
mg/dl) with atorvastatin 80 mg. Among patients receiving atorvastatin 10 mg, the
presence of each individual metabolic syndrome component significantly increased
the risk of major cardiovascular events compared with the absence of each (BMI, p
= 0.014; triglycerides, p = 0.006; HDL cholesterol, p = 0.0006; hypertension, p <
0.0001; and fasting glucose p < 0.0001). In patients receiving atorvastatin 80
mg, elevated triglycerides and fasting glucose were no longer significant
predictors of major cardiovascular events. The predictive power of hypertension
on the risk of major cardiovascular events was reduced in patients treated with
atorvastatin 80 mg, although it remained a significant predictor. CONCLUSIONS:
Treatment with high-dose atorvastatin to a mean LDL cholesterol level of 2.0
mmol/l (77 mg/dl) considerably attenuated the predictive power associated with
three metabolic syndrome components.
PMID- 26434402
TI - Mechanisms and mediators of lung injury after acute kidney injury.
AB - Acute kidney injury (AKI) is a common complication in hospitalized patients,
associated with >50% mortality in those in intensive care who require renal
replacement therapy. Data suggest that AKI is a systemic disease that adversely
affects the immune system and organ function, and in this way contributes to the
high mortality observed in affected patients. Data from patients and animal
models indicate that AKI adversely affects the lungs. Respiratory complications
are common in patients with AKI and include pulmonary oedema, respiratory failure
requiring mechanical ventilation, prolonged duration of mechanical ventilation,
and prolonged weaning from mechanical ventilation. The development of respiratory
failure in patients with AKI greatly increases the risk of death. Data from
animal models support the notion that cardiogenic pulmonary oedema (from volume
overload) and non-cardiogenic pulmonary oedema (from endothelial injury due to
inflammation and apoptosis) can occur in AKI. In this Review we discuss the
clinical, epidemiologic, and animal data that provide insights into the
mechanisms by which AKI can lead to lung injury and respiratory complications.
Elucidation of the mechanisms of lung injury and respiratory complications after
AKI is essential to develop effective therapies and reduce the high mortality
associated with AKI and respiratory failure.
PMID- 26434405
TI - A pH-mediated enhancement of the graphene carbocatalyst activity for the
reduction of 4-nitrophenol.
AB - Using alkaline pH adjustment, the reaction between graphene oxide and L-ascorbic
acid led to the formation of a carbocatalyst film with numerous graphene edges
protruding out of basal planes, which had a markedly enhanced carbocatalytic
activity for conversion of 4-nitrophenol to 4-aminophenol, as compared to that of
the carbocatalyst counterpart without involving pH mediation.
PMID- 26434407
TI - Pauli Spin Blockade of Heavy Holes in a Silicon Double Quantum Dot.
AB - In this work, we study hole transport in a planar silicon metal-oxide
semiconductor based double quantum dot. We demonstrate Pauli spin blockade in the
few hole regime and map the spin relaxation induced leakage current as a function
of interdot level spacing and magnetic field. With varied interdot tunnel
coupling, we can identify different dominant spin relaxation mechanisms.
Application of a strong out-of-plane magnetic field causes an avoided singlet
triplet level crossing, from which the heavy hole g-factor ~0.93 and the strength
of spin-orbit interaction ~110 MUeV can be obtained. The demonstrated strong spin
orbit interaction of heavy holes promises fast local spin manipulation using only
electric fields, which is of great interest for quantum information processing.
PMID- 26434408
TI - Right hippocampus size is negatively correlated with leptin serum levels in
bipolar disorder.
AB - Obesity is more frequent in bipolar disorder. Adipokines are associated with
depression and obesity via the inflammatory process. Twenty-six DSM-IV patients
with BD and 39 controls were enrolled to assess the relationship between serum
leptin and adiponectin with hippocampal volumes. Among patients, there was a
significant negative correlation between right hippocampal volume and serum
leptin levels. This result sum for the hypothesis of a pro-inflammatory state
associated with BD and the prevalent co-morbid obesity.
PMID- 26434409
TI - Silibinin suppresses astroglial activation in a mouse model of acute Parkinson's
disease by modulating the ERK and JNK signaling pathways.
AB - Parkinson's disease (PD) is the second-most common neurodegenerative disease
after Alzheimer's disease, and is characterized by dopaminergic neuronal loss in
midbrain. The MPTP-induced PD model has been well characterized by motor deficits
and selective dopaminergic neuronal death accompanied by glial activation.
Silibinin is a constituent of silymarin, an extract of milk thistle seeds, and
has been proposed to have hepatoprotective, anti-cancer, anti-oxidative, and
neuroprotective effects. In the present study, the authors studied the
neuroprotective effects of silibinin in an acute MPTP model of PD. Silibinin was
administered for 2 weeks, and then MPTP was administered to mice over 1 day
(acute MPTP induced PD). Silibinin pretreatment effectively ameliorated motor
dysfunction, dopaminergic neuronal loss, and glial activations caused by MPTP. In
addition, an in vitro study demonstrated that silibinin suppressed astroglial
activation and ERK and JNK phosphorylation in primary astrocytes in response to
MPP(+) treatment. These findings show silibinin protected dopaminergic neurons in
an acute MPTP-induced mouse model of PD, and suggest its neuroprotective effects
might be mediated by the suppression of astrocyte activation via the inhibition
of ERK and JNK phosphorylation. In conclusion, the study indicates silibinin
should be viewed as a potential treatment for PD and other neurodegenerative
diseases associated with neuroinflammation.
PMID- 26434410
TI - Outcomes of living donor renal transplantation in children with lower urinary
tract dysfunction: a comparative retrospective study.
AB - OBJECTIVES: To compare outcomes of renal transplantation (RTx) in children with
end-stage renal disease (ESRD) resulting from lower urinary tract dysfunction
(LUTD) vs other causes. PATIENTS AND METHODS: A database of children (<18 years
old) who underwent RTx between May 2008 and April 2012 was reviewed. Patients
were divided into those with LUTD (group A, n = 29) and those with other causes
of ESRD (group B, n = 74). RTx was performed after achieving low intravesical
pressure (<30 cmH2 O) with adequate bladder capacity and drainage. The groups
were compared using Student's t-test, Mann-Whitney, chi-squared or exact tests.
Graft survival rates (GSRs) were evaluated using Kaplan-Meier curves and the log
rank test. RESULTS: The mean +/- sd (range) age of the study cohort was 5.05 +/-
12.4 (2.2-18) years. Causes of LUTD were posterior urethral valve (PUV; 41.4%),
vesico-ureteric reflux (VUR; 37.9%), neurogenic bladder (10.3%), prune belly
syndrome (3.4%), obstructive megaureter (3.4%) and urethral stricture disease
(3.4%). There was no significant difference in age, dialysis duration or donor
type. In group A, 25 of the 29 patients (86.2%) underwent >=1 surgery to optimize
the urinary tract for allograft. Pretransplant nephrectomy was performed in 15 of
the 29 patients (51.7%), PUV ablation in nine patients (31%) and ileocystoplasty
in four patients (13.7%). The mean +/- sd follow-up was 4.52 +/- 1.55 and 4.07 +/
1.27 years in groups A and B, respectively. There was no significant difference
in creatinine and eGFR between the groups at different points of follow-up. The
GSRs at the end of the study were 93.1 and 91.1% in groups A and B, respectively
(P = 1.00). According to Kaplan-Meier survival curves, there was no significant
difference in the GSR between the groups using the log-rank test (P = 0.503). No
graft was lost as a result of urological complications. In group B, one child
died from septicaemia. The rate of urinary tract infections was 24 and 12% in
groups A and B, respectively, but was not significant. No significant difference
was found between the groups with regard to the incidence of post-transplantation
hydronephrosis. Of the 22 patients who had hydronephrosis after transplantation,
three were complicated by UTI. Injection of bulking agents was required in two
patients for treatment of grade 3 VUR. In the third patient, augmentation
cystoplasty was needed. CONCLUSION: Acceptable graft function, survival and UTI
rates can be achieved in children with ESRD attributable to LUTD. Thorough
assessment and optimization of LUT, together with close follow-up, are key for
successful RTx.
PMID- 26434412
TI - MALAT1 long non-coding RNA in cancer.
AB - A recent massive parallel sequencing analysis has shown the fact that more than
80% of the human genome is transcribed into RNA. Among many kinds of the non
protein coding RNAs, we focus on the metastasis associated lung adenocarcinoma
transcript 1 (MALAT1) that is a long non-coding RNA upregulated in metastatic
carcinoma cells. Two molecular functions of MALAT1 have been proposed, one is the
control of alternative splicing and the other is the transcriptional regulation.
In this review, we document the molecular characteristics and functions of MALAT1
and shed light on the implication in the molecular pathology of various cancers.
This article is part of a Special Issue entitled: Clues to long noncoding RNA
taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.
PMID- 26434411
TI - Linkage and regional association analysis reveal two new tightly-linked major
QTLs for pod number and seed number per pod in rapeseed (Brassica napus L.).
AB - To facilitate the pseudochromosomes assembly and gene cloning in rapeseed, we
developed a reference genetic population/map (named BnaZNF2) from two sequenced
cultivars, Zhongshuang11 and No.73290, those exhibit significant differences in
many traits, particularly yield components. The BnaZNF2 genetic map exhibited
perfect collinearity with the physical map of B. napus, indicating its high
quality. Comparative mapping revealed several genomic rearrangements between B.
napus and B. rapa or B. oleracea. A total of eight and 16 QTLs were identified
for pod number and seed number per pod, respectively, and of which three and five
QTLs are identical to previously identified ones, whereas the other five and 11
are novel. Two new major QTL respectively for pod number and seed number per pod,
qPN.A06-1 and qSN.A06-1 (R(2 )= 22.8% and 32.1%), were colocalised with opposite
effects, and only qPN.A06-1 was confirmed and narrowed by regional association
analysis to 180 kb including only 33 annotated genes. Conditional QTL analysis
and subsequent NILs test indicated that tight linkage, rather than pleiotropy,
was the genetic causation of their colocalisation. Our study demonstrates
potential of this reference genetic population/map for precise QTL mapping and as
a base for positional gene cloning in rapeseed.
PMID- 26434413
TI - Untangling reaction pathways through modern approaches to high-throughput single
molecule force-spectroscopy experiments.
AB - Single-molecule experiments provide a unique means for real-time observation of
the activity of individual biomolecular machines. Through such techniques,
insights into the mechanics of for example, polymerases, helicases, and packaging
motors have been gleaned. Here we describe the recent advances in single-molecule
force spectroscopy instrumentation that have facilitated high-throughput
acquisition at high spatiotemporal resolution. The large datasets attained by
such methods can capture rare but important events, and contain information
regarding stochastic behaviors covering many orders of magnitude in time. We
further discuss analysis of such data sets, and with a special focus on the pause
states described in the general literature on RNA polymerase pausing we compare
and contrast the signatures of different reaction pathways.
PMID- 26434414
TI - Current harmonics elimination control method for six-phase PM synchronous motor
drives.
AB - To reduce the undesired 5th and 7th stator harmonic current in the six-phase
permanent magnet synchronous motor (PMSM), an improved vector control algorithm
was proposed based on vector space decomposition (VSD) transformation method,
which can control the fundamental and harmonic subspace separately. To improve
the traditional VSD technology, a novel synchronous rotating coordinate
transformation matrix was presented in this paper, and only using the traditional
PI controller in d-q subspace can meet the non-static difference adjustment, the
controller parameter design method is given by employing internal model
principle. Moreover, the current PI controller parallel with resonant controller
is employed in x-y subspace to realize the specific 5th and 7th harmonic
component compensation. In addition, a new six-phase SVPWM algorithm based on VSD
transformation theory is also proposed. Simulation and experimental results
verify the effectiveness of current decoupling vector controller.
PMID- 26434415
TI - New passivity criteria for memristive uncertain neural networks with leakage and
time-varying delays.
AB - In this paper, the problem of passivity analysis is studied for memristor-based
uncertain neural networks with leakage and time-varying delays. By combining
differential inclusions with set-valued maps, the system of memristive neural
networks is changed into the conventional one. By adding a triple quadratic
integral and relaxing the requirement for the positive definiteness of some
matrices, a proper Lyapunov-Krasovskii functional is constructed. Based on the
establishment of the novel Lyapunov-Krasovskii functional, the new passivity
criteria are derived by mainly applying Wirtinger-based double integral
inequality, S-procedure and so on. Moreover, the conservatism of passivity
conditions can be reduced. Finally, four numerical examples are given to show the
effectiveness and less conservatism of the proposed criteria.
PMID- 26434416
TI - Colorimetric detection of hazardous gases using a remotely operated capturing and
processing system.
AB - This paper presents an electronic system for the automatic detection of hazardous
gases. The proposed system implements colorimetric sensing algorithms, thus
providing a low-cost solution to the problem of gas sensing. It is remotely
operated and it performs the tasks of image capturing and processing, hence
obtaining colour measurements in RGB (Red-Green-Blue) space that are subsequently
sent to a remote operator via the internet. A prototype of the system has been
built to test its performance. Specifically, experiments have been carried out
aimed at the detection of CO, CO2, NO, NO2, SO2 and formaldehyde at diverse
concentrations by using a chromogenic array composed by 13 active and 2 inert
compounds. Statistical analyses of the results reveal a good performance of the
electronic system and the feasibility of remote hazardous gas detection using
colorimetric sensor arrays.
PMID- 26434418
TI - A composite control method based on the adaptive RBFNN feedback control and the
ESO for two-axis inertially stabilized platforms.
AB - Due to the nonlinearity and time variation of a two-axis inertially stabilized
platform (ISP) system, the conventional feedback control cannot be utilized
directly. To realize the control performance with fast dynamic response and high
stabilization precision, the dynamic model of the ISP system is expected to match
the ideal model which satisfies the desired control performance. Therefore, a
composite control method based on the adaptive radial basis function neural
network (RBFNN) feedback control and the extended state observer (ESO), is
proposed for ISP. The adaptive RBFNN is proposed to generate the feedback control
parameters online. Based on the state error information in the working process,
the adaptive RBFNN can be constructed and optimized directly. Therefore, no
priori training data is needed for the construction of the RBFNN. Furthermore, a
linear second-order ESO is constructed to compensate for the composite
disturbance. The asymptotic stability of the proposed control method has been
proven by the Lyapunov stability theory. The applicability of the proposed method
is validated by a series of simulations and flight tests.
PMID- 26434417
TI - Finite-time stabilization of uncertain nonholonomic systems in feedforward-like
form by output feedback.
AB - This paper investigates the problem of finite-time stabilization by output
feedback for a class of nonholonomic systems in chained form with uncertainties.
Comparing with the existing relevant literature, a distinguishing feature of the
systems under investigation is that the x-subsystem is a feedforward-like rather
than feedback-like system. This renders the existing control methods inapplicable
to the control problems of the systems. A constructive design procedure for
output feedback control is given. The designed controller renders that the states
of closed-loop system are regulated to zero in a finite time. Two simulation
examples are provided to illustrate the effectiveness of the proposed approach.
PMID- 26434419
TI - Causal role of oxidative stress in unfolded protein response development in the
hyperthyroid state.
AB - L-3,3',5-Triiodothyronine (T3)-induced liver oxidative stress underlies
significant protein oxidation, which may trigger the unfolded protein response
(UPR). Administration of daily doses of 0.1mg T3 for three consecutive days
significantly increased the rectal temperature of rats and liver O2 consumption
rate, with higher protein carbonyl and 8-isoprostane levels, glutathione
depletion, and absence of morphological changes in liver parenchyma.
Concomitantly, liver protein kinase RNA-like endoplasmic reticulum (ER) kinase
and eukaryotic translation initiator factor 2alpha were phosphorylated in T3
treated rats compared to controls, with increased protein levels of binding
immunoglobulin protein and activating transcription factor 4. In addition, higher
mRNA levels of C/EBP homologous protein, growth arrest and DNA damage 34, protein
disulfide isomerase, and ER oxidoreductin 1alpha were observed, changes that were
suppressed by N-acetylcysteine (0.5 g/kg) given before each dose of T3. In
conclusion, T3-induced liver oxidative stress involving higher protein oxidation
status has a causal role in UPR development, a response that is aimed to
alleviate ER stress and promote cell survival.
PMID- 26434420
TI - A review of case-control studies on the risk factors for the development of
autoimmune blistering diseases.
AB - Autoimmune blistering diseases (AIBD) are a group of rare but potentially fatal
diseases characterized by the production of autoantibodies directed against the
structural proteins of the skin. Much has been published on the clinical
manifestation and interventional options for AIBD, especially on the more common
subtypes such as bullous pemphigoid, pemphigus vulgaris (PV) and pemphigus
foliaceus (PF). However, the aetiology of AIBD remains unknown. We aim to provide
an overview of published case-control studies focussing on the non-genetic
aetiological factors of bullous pemphigoid, PV and/or PF. The relevant studies
were appraised for their validity and results. Our results showed that a large
proportion of the studies had inconclusive results due to compromised study
methodologies. Moreover, there were no identified case-control studies that
investigated the possible associations between bullous pemphigoid and patient
environment, or the potential links between pemphigus and drugs. Hence, a case
control study with a higher quality design addressing these shortcomings would
contribute greatly to our knowledge of AIBD.
PMID- 26434421
TI - A population-based analysis of Head and Neck hemangiopericytoma.
AB - OBJECTIVES/HYPOTHESIS: Hemangiopericytomas (HPC) are tumors that arise from
pericytes. Hemangiopericytomas of the head and neck are rare and occur both
extracranially and intracranially. This study analyzes the demographic,
clinicopathologic, treatment modalities, and survival characteristics of
extracranial head and neck hemangiopericytomas (HN-HPC) and compares them to HPCs
at other body sites (Other-HPC). METHODS: The Surveillance, Epidemiology, and End
Results (SEER) database (1973-2012) was queried for HN-HPC (121 cases) and Other
HPC (510 cases). Data were analyzed comparatively with respect to various
demographic and clinicopathologic factors. Disease-specific survival (DSS) was
analyzed using the Kaplan-Meier model. RESULTS: There was no significant
difference in age at time of diagnosis between HN-HPC and Other-HPC. Head and
neck HPC was most commonly located in the connective and soft tissue (18.4%),
followed by the nasal cavity and paranasal sinuses (8.5%). Head and neck HPCs
were smaller than Other-HPC (P < 0.0001) and more likely to be a lower histologic
grade (P < 0.0097). The primary treatment modality for HN-HPC was surgery alone,
used in 55.8% of cases. The 5-, 10-, and 20-year DSS for HN-HPC were 84.0%,
79.4%, and 69.4%, respectfully. Higher histologic grade and the presence of
distant metastases were poor prognostic factors for HN-HPC. CONCLUSION: Head and
neck HPCs are rare tumors. This study represents the largest series of HN-HPCs to
date. Surgery alone is the primary treatment modality for HN-HPC, with a
favorable prognosis. Adjuvant radiotherapy does not appear to confer a survival
benefit for any body site. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:643-650, 2016.
PMID- 26434423
TI - SGR Repeal: Reprieve or Pyrrhic Victory?
AB - The United States Congress recently passed the bill titled H.R.2: the Medicare
Access and CHIP Reauthorization Act of 2015 (MACRA) to repeal the Sustainable
Growth Rate (SGR). The SGR, part of the Balanced Budget Act of 1997, was passed
to attempt to control the rate of growth for Medicare spending for physician
services. As a result, all physicians were annually subject to the aggregate cuts
in compensation depending on rate of economic growth in the country, requiring
Congress to pass legislation each year to defer the scheduled pay cuts. Will
MACRA, however, truly be a reprieve to providers from the threat of annual cuts
in reimbursement of between 21% and 30%, or will it result in a Pyrrhic victory
for both providers and patients after the financial impact of the repeal has been
realized and the quality of health care delivery and true access to care for our
seniors have been evaluated? This article from The Society of Thoracic Surgeons
Workforce on Health Policy, Advocacy, and Reform attempts to summarize MACRA and
considers its impact on the specialty of cardiothoracic surgery.
PMID- 26434422
TI - Introducing Policy Perspectives.
PMID- 26434424
TI - 50th Anniversary Perspective on Volume 1: Urschel HC, Paulson DL. Mesotheliomas
of the Pleura. Ann Thorac Surg 1965;1:559-73.
PMID- 26434425
TI - 50th Anniversary Landmark Commentary on Griffith BP, Hardesty RL, Trento A, et
al. Heart-lung transplantation: lessons learned and future hopes. Ann Thorac Surg
1987;43:6-16.
PMID- 26434426
TI - 50th Anniversary Landmark Commentary on Bender HW Jr, Stewart JR, Merrill WH,
Hammon JW Jr, Graham TP Jr. Ten years' experience with the Senning operation for
transposition of the great arteries: physiological results and late follow-up.
Ann Thorac Surg 1989;47:218-23.
PMID- 26434427
TI - 50th Anniversary Landmark Commentary on Ginsberg RJ, Pearson FG, Cooper JD, et
al. Closure of chronic postpneumonectomy bronchopleural fistula using the
transsternal transpericardial approach. Ann Thorac Surg 1989;47:231-5.
PMID- 26434428
TI - Invited Commentary.
PMID- 26434429
TI - Invited Commentary.
PMID- 26434430
TI - Invited Commentary.
PMID- 26434431
TI - Invited Commentary.
PMID- 26434432
TI - Invited Commentary.
PMID- 26434433
TI - Invited Commentary.
PMID- 26434434
TI - Invited Commentary.
PMID- 26434435
TI - Invited Commentary.
PMID- 26434436
TI - Invited Commentary.
PMID- 26434437
TI - Invited Commentary.
PMID- 26434438
TI - Anomalous Origin of the Circumflex Artery: An Underestimated Threat During Mitral
Valve Operation.
AB - Ischemic iatrogenic lesions can complicate surgical procedures on the mitral
valve. One of the causative mechanisms is direct injury to or distortion of the
circumflex coronary artery. The risk of damaging the circumflex coronary artery
depends mainly on the proximity of that vessel to the posterior segment of the
mitral annulus, and this varies from patient to patient. Herein, we report the
case of an iatrogenic circumflex coronary artery lesion after mitral annuloplasty
in a patient with an anomalous origin of the circumflex artery.
PMID- 26434439
TI - Aortic and Mitral Valve Replacement Due to Extensive Inflammatory Immunoglobulin
G4-Related Pseudotumor.
AB - A 64-year-old woman with extensive tumorous infiltration of the mitral and aortic
valves underwent partial resection of a tumor of the left ventricular outflow
tract and replacement of both affected valves. Histology revealed an inflammatory
pseudotumor with a significant number of immunoglobulin-G4-positive plasma cells.
The histologic and clinical findings suggested immunoglobulin-G4-related disease
of the heart.
PMID- 26434440
TI - Severely Thrombosed Transcatheter Aortic Valve 9 Months After Implantation.
AB - Bioprosthetic aortic valve thrombosis is a rare complication after transcatheter
aortic valve implantation; however, one with a high mortality. We describe the
case of a patient with a completely thrombosed transcatheter aortic valve
prosthesis 9 months after implantation and review the diagnosis and management of
this complication.
PMID- 26434441
TI - Endovascular Repair for Type A Aortic Dissection After Transcatheter Aortic Valve
Replacement With a Medtronic CoreValve.
AB - Transcatheter aortic valve replacement is being used with increasing frequency in
patients with severe aortic stenosis who are otherwise deemed to be at high
surgical risk. Aortic dissection is a rare complication of transcatheter aortic
valve replacement and poses a unique management dilemma. We describe the
treatment of an acute Stanford type A aortic dissection after transcatheter
aortic valve replacement with a modified thoracic endovascular stent graft in a
95-year-old woman.
PMID- 26434442
TI - Modified Senning Procedure for Correction of Atrioventricular Discordance With
Total Anomalous Pulmonary Venous Return, Atrial Situs Inversus, Dextrocardia, and
Bilateral Superior Venae Cavae.
AB - The Senning and Mustard baffles remain important techniques for the treatment of
congenitally corrected transposition (cc-TGA), isolated ventricular inversion,
and D-transposition of the great arteries with delayed presentation. We describe
the treatment of an 8-month old infant with atrioventricular discordance,
ventriculoarterial concordance, and dextrocardia with atrial situs inversus. A
modified Senning procedure was performed through the "left-sided" atrium.
Modifications of the Senning and Mustard baffles remain important tools in the
treatment of rare conditions like isolated ventricular inversion.
PMID- 26434443
TI - Metastatic Ocular Melanoma Presenting as a Heart-Compressing Mediastinal Mass.
AB - Ocular malignant melanoma is characterized by an unpredictable course, and
metastases may develop, after a long disease-free interval, anywhere in the body.
The mediastinum, however, is a rare site of these metastases, and metastatic
melanoma presenting as a large mediastinal mass is quite unusual. We report
herein a peculiar case of a solitary, late metastasis of malignant ocular
melanoma, manifesting as a sizable posterior mediastinal mass and presenting with
paroxysmal atrial fibrillation. Transthoracic echocardiography, computed
tomography scan findings, and surgical treatment and pathologic examination are
described.
PMID- 26434444
TI - Congenital Absence of One Pulmonary Valve Cusp With Other Hypoplastic Cusps.
AB - Congenital absence of a single pulmonary valve cusp is extremely rare. We report
a case of a 38-year-old woman with a confirmed congenital absence of a single
pulmonary valve cusp associated with dextrocardia. The other 2 leaflets were
moderately hypoplastic, and transthoracic echocardiography showed severe
pulmonary regurgitation. This combination of lesions has not been reported
previously. Pulmonary valve replacement using a composite biologic valved conduit
was performed with an excellent outcome.
PMID- 26434445
TI - Novel Cannulation Strategy for Repair of an Ascending Aortic Pseudoaneurysm in a
2.8-kg Infant.
AB - Pseudoaneurysm of the ascending aorta is rare in infants, with few cases reported
in the literature. These aneurysms are usually mycotic, occurring after cardiac
surgery, or caused by mediastinitis. They have high risk of spontaneous rupture.
Surgery is usually complex because of the need for peripheral cannulation in
small infants. We report an ascending aortic pseudoaneurysm in a less than 3
month-old infant that occurred within a month after repair of type 2 truncus
arteriosus and was managed successfully with a modified cardiopulmonary bypass
strategy.
PMID- 26434446
TI - Endobronchial Primitive Neuroectodermal Tumor With Pneumothorax Ex Vacuo.
AB - We experienced a rare case of an endobronchial primitive neuroectodermal tumor of
the left main bronchus. Initially we suspected pneumothorax caused by a collapsed
left upper lobe and an air-entrapped lower lobe. After tube thoracostomy, the
pneumothorax persisted without air leakage. A tumor was detected at the left main
bronchus on computed tomography and bronchoscopy, and diagnosed pathologically as
small cell lung cancer. Under the presumed diagnosis of limited-stage small cell
lung cancer, we performed a left pneumonectomy. The tumor was eventually
identified pathologically as a primitive neuroectodermal tumor. Although adjuvant
chemoradiotherapy was not performed, no recurrence was observed.
PMID- 26434447
TI - Severe Pulmonary Valve Regurgitation 40 Years After Blunt Chest Trauma.
AB - Severe pulmonary valve regurgitation caused by a pulmonary valve tear is a rare
complication to a blunt chest trauma. In this case report, we present a patient
with pulmonary regurgitation originating from a chest trauma 40 years ago.
Possible mechanisms are osseous pinch of the pulmonary valve between the anterior
chest wall and the vertebral column, and retrograde blowout from severe
compression of the lungs.
PMID- 26434448
TI - Successful Primary Repair of a Colopericardial Fistula: A Late Complication of
Esophageal Replacement.
AB - Colopericardial fistula after colonic interposition is a rare complication, with
few prior reported cases. Management of such cases has usually consisted of
resection of the colonic segment with cervical diversion. Here we present a case
of successful primary repair of a colopericardial fistula in a 73-year-old woman
who had initially undergone a colonic interposition graft 30 years before
presentation.
PMID- 26434449
TI - Thoracoscopic Excision of Migrated Kirschner Wire to Right Pulmonary Hilum.
AB - Kirschner wires are often used for the stabilization of complex fractures. Wire
migration is a rare but still recognized complication of its use. A 56-year-old
man suffered a clavicle fracture at age 26 that was stabilized with one Kirschner
wire, and for 30 years he was asymptomatic. Recently, he presented with cough and
right thoracic pain. Chest radiographs revealed migration of the Kirschner wire,
and thoracoscopic visualization revealed that the Kirschner wire had penetrated
the middle lobe parenchyma and was in close contact with the right auricle. This
case study reports the successful thoracoscopic treatment of a rare complication
of Kirschner wire migration.
PMID- 26434450
TI - Arteriovenous Fistula: A Rare Complication After Nuss Procedure for Pectus
Excavatum.
AB - We report a case of a 13-year-old female patient who underwent the Nuss procedure
for surgical correction of pectus excavatum. As a result of the procedure, the
patient developed an arteriovenous fistula between the left internal mammary
artery and the pulmonary venous system.
PMID- 26434451
TI - Spontaneous Regression of Metastatic Extraskeletal Myxoid Chondrosarcoma.
AB - Spontaneous regression of tumors is very unusual and is defined as a partial or
complete disappearance of metastatic tumors without any treatment. This
phenomenon has been reported in almost all types of cancer. The patient was a 25
year-old woman who presented with multiple pulmonary nodules on her bilateral
lungs on the annual chest roentgenograph. Simultaneously, a swelling mass on her
subcutaneous inguinal region was observed. The diagnosis of the inguinal mass was
extraskeletal myxoid chondrosarcoma. The inguinal mass and pulmonary nodules
spontaneously regressed without any treatment after biopsy. The patient was doing
well without evidence of recurrence at 1 year after the operation without any
additional therapy. Our case is the first clinical one that indicated a
possibility of histologic regression of extraskeletal myxoid chondrosarcoma.
PMID- 26434452
TI - Surgical Treatment in a Case of Cogan's Syndrome Complicated With Proximal Aortic
Vasculitis.
AB - Cogan's syndrome is a rare idiopathic inflammatory disease with involvement of
the eye and inner ear. This syndrome can be associated with aortic root
vasculitis. We report the case of a young man with a history of uveitis and
bilateral hearing loss who presented with proximal aortic vasculitis and
dilatation after aortic valve replacement. Cogan's syndrome was diagnosed on the
basis of large artery vasculitis with typical vestibuloauditory and ocular
involvement. The patient underwent successful a Bentall operation after aortic
valve replacement.
PMID- 26434453
TI - Acute Aortic Dissection Associated With Pregnancy.
PMID- 26434454
TI - Right Ventricular Perforation Caused by a Pacing Catheter Two Weeks After
Insertion in a Neonate With Congenital Atrioventricular Block.
PMID- 26434455
TI - Mobile Thoracolithiasis in a Patient With Lung Cancer.
PMID- 26434456
TI - Skeletonization of the Recurrent Laryngeal Nerve During Norwood Procedure and
Aortic Arch Repair.
AB - Recurrent laryngeal nerve injury is a frequent adverse event of aortic arch
repair. We hereby present a technique of skeletonization of the recurrent nerve
to preserve its function during the Norwood procedure and aortic arch repair.
PMID- 26434457
TI - Easy and Safe Total Debranching of Arch Aneurysms Using Axilloaxillary Arterial
Bypass.
AB - Techniques used in hybrid repair of proximal aortic arch diseases are associated
with perioperative complications such as cerebrovascular emboli. We present an
easy and safe technique of total debranching thoracic endovascular aortic repair
for arch diseases using axilloaxillary arterial bypass. The placement of the
axilloaxillary arterial bypass enables perfusion of the brachiocephalic artery
even when the artery is clamped. After reconstruction of the brachiocephalic
artery and the left common carotid artery, the left subclavian artery is
proximally ligated, and it is perfused through the bypass. This procedure is
simple, safe, and useful for the prevention of neurologic complications.
PMID- 26434458
TI - Arena Roof Technique for Complex Reconstruction After Extensive Chest Wall
Resection.
AB - Extensive primary resections or redos may produce significant chest wall defects
requiring creative reconstructions in order to avoid reduction of the
intrathoracic volume. We describe the successful use of an innovative technique
for chest wall reconstruction based on the concept of roof coverage of sport
arenas. In fact, titanium plates are anchored to the residual rib stumps along
the parasternal and paravertebral lines. The acellular collagen matrix prosthesis
was sutured to the free edges of the same titanium plates to create a roof,
reproducing the chest wall dome geometric configuration. A 36-year-old female
patient was diagnosed with an extensive desmoid tumor involving the lateral
segments of second to fifth ribs on the right side. The arena roof technique
allowed for adequate expansion of the uninvolved lung and optimal chest wall
functional recovery.
PMID- 26434459
TI - An Easy Modification of Tube Graft Interposition During Fenestration in
Borderline Fontan Circulation.
AB - One of the options for the management of borderline/failing extracardiac Fontan
circulation is surgical creation of an atrial fenestration to decompress the
systemic venous compartment and improve cardiac output. Depending on the body
surface area of the patient, a 5- to 10-mm polytetrafluoroethylene (PTFE) tube
graft can be used. When fenestration is required in a patient with failing Fontan
circulation, particularly in redo cases, application of a side-biting clamp may
be challenging because of adhesions and a thickened atrial wall. In this article,
we present our off-pump technique of atrial-side anastomosis of PTFE graft
interposition between an extracardiac Fontan conduit and the atrium without using
a side-biting clamp.
PMID- 26434460
TI - Chest Wall Surgery: Less Arbitrium, More Science.
PMID- 26434461
TI - Antegrade Cerebral Perfusion.
PMID- 26434462
TI - What Really Affects Synchronous Pulmonary Adenocarcinoma Management?
PMID- 26434463
TI - Severity of Angina Is a Predictor of Long-Term Improvement of Quality of Life
After Coronary Artery Bypass Grafting.
PMID- 26434464
TI - Reply: To PMID 25443005.
PMID- 26434465
TI - Regarding Freestyle Pseudoaneurysms.
PMID- 26434466
TI - Extrapleural Pneumonectomy and Pleurectomy Decortication: Can We Really Compare
Their Survival?
PMID- 26434467
TI - Reply: To PMID 25301369.
PMID- 26434468
TI - Personalized Aortic Root Support With Mesh Provides Optimal Valve Conservation.
PMID- 26434469
TI - Reply: To PMID 25534527.
PMID- 26434470
TI - What Can We Do to Reduce Hospital Readmission After Lung Lobectomy?
PMID- 26434471
TI - Reply: To PMID 25662437.
PMID- 26434472
TI - Reply: To PMID 25497070.
PMID- 26434473
TI - Reply: To PMID 25499482.
PMID- 26434474
TI - Should We Discontinue Intraaortic Balloon During Cardioplegic Arrest? Our Old But
Still Open Question.
PMID- 26434475
TI - Reply: To PMID 25633461.
PMID- 26434476
TI - Is TNM Alone Enough to Predict Prognosis in Lung Adenocarcinomas?
PMID- 26434477
TI - Simultaneous Carotid Artery Stenting Combined With Open Heart Surgery: Another
Indication.
PMID- 26434478
TI - Reply: To PMID 25661578.
PMID- 26434479
TI - The Left Thoracotomy Approach for Oncologic Esophageal Resection Is Still
Relevant for the Modern Surgical Trainee.
PMID- 26434480
TI - Reply: To PMID 24650587.
PMID- 26434481
TI - Percutaneous SAPIEN S3 Transcatheter Valve Implantation for Post-Left Ventricular
Assist Device Aortic Regurgitation.
AB - Aortic regurgitation was found to develop in a considerable share of patients
supported with continuous flow left ventricular assist devices (LVADs). The
resulting circulatory loop renders LVAD operation inefficient so that symptoms of
heart failure develop in spite of high LVAD flows. In patients with a high
reoperative risk, transcatheter aortic valve implantation may be considered as an
alternative to reoperative valve surgical procedures. We report a case of
percutaneous transcatheter aortic valve implantation using the SAPIEN S3 (Edwards
Lifesciences, Inc, Irvine, CA) valve for post-LVAD aortic regurgitation.
PMID- 26434482
TI - Primary Endoscopic Repair of a Large Tracheal Rupture Through Tracheal Stoma.
AB - We describe the case of an 83-year-old man who presented with a large trauma to
the membranous wall of the trachea and was treated with endoscopic primary repair
of the tracheal wall through a preexisting tracheal stoma. Assessment with an
optical telescope through the tracheal stoma revealed a 5-cm laceration in the
membranous wall of the trachea starting immediately above the carina. The
laceration was closed using continuous 4-0 monofilament polydioxanone sutures
with direct visualization of tissues through a fiberoptic telescope. This
approach is particularly effective in cases of traumatic rupture of the
membranous trachea.
PMID- 26434483
TI - A Case Series of Biventricular Circulatory Support Using Two Ventricular Assist
Devices: A Novel Operative Approach.
AB - Increased use of continuous-flow left ventricular assist devices (LVADs) to treat
advanced heart failure has heightened concern for right ventricular failure after
LVAD implantation, which is associated with increased morbidity and mortality.
Biventricular support is required in up to 30% of LVAD recipients. Currently, no
durable long-term right ventricular assist device (RVAD) has been approved other
than the Syncardia (Tucson, AZ) total artificial heart. A recent publication
reported the placement of continuous flow LVAD in the heavily trabeculated right
ventricle; however, this orientation may jeopardize both assist device and right
ventricle function. We describe three cases of right-sided mechanical circulatory
support with durable RVAD implanted in the right atrium, allowing long-term
support with fewer anatomic limitations as compared with right ventricular
cannulation.
PMID- 26434484
TI - Mediastinal Bronchogenic Cyst With Acute Cardiac Dysfunction: Two-Stage Surgical
Approach.
AB - We describe a two-stage surgical approach in a patient with cardiac dysfunction
and hemodynamic compromise resulting from a massive and compressive mediastinal
bronchogenic cyst. To drain this cyst, video-assisted mediastinoscopy was
performed as an emergency procedure, which immediately improved the patient's
cardiac function. Five days later and under video thoracoscopy, resection of the
cyst margins was impossible because the cyst was tightly adherent to the left
atrium. We performed deroofing of this cyst through a right thoracotomy. The
patient had an uncomplicated postoperative recovery, and no recurrence was
observed at the long-term follow-up visit.
PMID- 26434485
TI - Novel Use of External Tissue Expander for Management of Sternal Wound Dehiscence.
AB - Sternal wound dehiscence and its associated complications contribute to
significant morbidity and mortality after coronary bypass operations. We present
the novel use of continuous external tissue expansion to achieve delayed primary
closure of a previously dehisced sternal wound.
PMID- 26434486
TI - Primary Sternal Osteomyelitis With Extensive Mediastinal Abscess in a Neonate.
AB - Sternal osteomyelitis is extremely rare in neonates. We present the first report
of a neonate with primary sternal osteomyelitis and an extensive mediastinal
collection. Magnetic resonance imaging was used to delineate the extent of bony
and soft tissue involvement. Serial ultrasound imaging proved useful for
monitoring the response to treatment. The patient was successfully treated with
antibiotics, surgical debridement, vacuum-assisted dressings, and delayed primary
closure.
PMID- 26434487
TI - Idiopathic Pseudoaneurysm of the Mitral-Aortic Intervalvular Fibrosa.
AB - The mitral-aortic intervalvular fibrosa is an avascular fibrous structure between
the anterior mitral leaflet and the aortic annulus. Pseudoaneurysm formation of
the mitral-aortic intervalvular fibrosa is a rare but known entity most commonly
caused by infective endocarditis or valve surgery. We present a 29-year-old
patient with a mitral-aortic intervalvular fibrosa pseudoaneurysm of no evident
cause who was successfully managed surgically.
PMID- 26434488
TI - Left Ventricular Assist Device End-to-End Connection to the Left Subclavian
Artery: An Alternative Technique.
AB - We describe a modified implantation technique for the HeartWare ventricular
assist device. We access the apex through a left minithoracotomy. The outflow
graft is tunneled through a small incision in the fourth intercostal space and
then subcutaneously to the subclavian region. After division of the left axillary
artery, an end-to-end anastomosis is performed to the proximal part, and the
distal vessel is connected end-to-side through a fenestration in the outflow
graft. We believe that this technique, particularly suitable for redo scenarios
or severely calcified aorta, achieves a more direct blood flow into the aorta and
reduces cerebrovascular events while avoiding excessive flow to the arm.
PMID- 26434489
TI - Brugia malayi soluble and excretory-secretory proteins attenuate development of
streptozotocin-induced type 1 diabetes in mice.
AB - Understanding the modulation of the host-immune system by pathogens-like filarial
parasites offers an alternate approach to prevent autoimmune diseases. In this
study, we have shown that treatment with filarial proteins prior to or after the
clinical onset of streptozotocin-induced type-1 diabetes (T1D) can ameliorate the
severity of disease in BALB/c mice. Pre-treatment with Brugia malayi adult
soluble (Bm A S) or microfilarial excretory-secretory (Bm mf ES) or microfilarial
soluble (Bm mf S) antigens followed by induction of diabetes led to lowering of
fasting blood glucose levels with as many as 57.5-62.5% of mice remaining
nondiabetic. These proteins were more effective when they were used to treat the
mice with established T1D as 62.5-71.5% of the mice turned to be nondiabetic.
Histopathological examination of pancreas of treated mice showed minor
inflammatory changes in pancreatic islet cell architecture. The therapeutic
effect was found to be associated with the decreased production of cytokines TNF
alpha & IFN-gamma and increased production of IL-10 in the culture supernatants
of splenocytes of treated mice. A switch in the production of anti-insulin
antibodies from IgG2a to IgG1 isotype was also seen. Together these results
provide a proof towards utilizing the filarial derived proteins as novel anti
diabetic therapeutics.
PMID- 26434490
TI - The impact of perioperative dexamethasone on swallowing impairment score after
thyroidectomy: a retrospective study of 118 total thyroidectomies.
PMID- 26434493
TI - Difference of concentration of placental soluble fms-like tyrosine kinase-1(sFlt
1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in severe preeclampsia
and normal pregnancy.
AB - BACKGROUND: Placental soluble fms-like tyrosine kinase-1 (sFlt-1) which is an
antagonist of vascular endothelial growth factor and placental growth factor
(PIGF), is considered as one of etiology factors cause endothelial damage in
preeclampsia due to increase of sFlt-1 level that change vascular endothelial
integrity. This study aims to analyze the difference of sFlt-1 and PlGF
concentration in severe preeclampsia and normal pregnancy, and the correlation
between both in occurrence of severe preeclampsia. METHOD: This is case control
study involving 18 subjects with severe preeclampsia and 19 subjects with normal
pregnancy as controls who met inclusion and exclusion criteria. Concentration of
sFlt-1 and PlGF are measured with ELISA. Statistical analysis is performed with
Chi square test, Fisher's exact test, T test, Mann-Whitney test, and Spearman's
rank correlation test. RESULTS: This study results in no significant difference
in characteristics of gestational age, and parity in both study groups. Median
concentration of sFlt-1 in severe preeclampsia is higher (20,524.75 pg/mL)
compared with normal pregnancy (6820.4 pg/mL). Concentration of PlGF is lower in
severe preeclampsia (47 pg/mL) compared with normal pregnancy (337 pg/mL). sFlt-1
concentration is higher in severe preeclampsia compared to normal pregnancy. PlGF
concentration is lower in severe preeclampsia compared to normal pregnancy. Ratio
of sFlt-1 and PlGF concentration is significantly correlated in both severe
preeclampsia and normal pregnancy. CONCLUSIONS: There is a significant negative
correlation between the concentration of sFLt-1 and PlGF in normal pregnancy.
PMID- 26434492
TI - Enhanced Production of Adenosine Triphosphate by Pharmacological Activation of
Adenosine Monophosphate-Activated Protein Kinase Ameliorates Acetaminophen
Induced Liver Injury.
AB - The hepatic cell death induced by acetaminophen (APAP) is closely related to
cellular adenosine triphosphate (ATP) depletion, which is mainly caused by
mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase
(AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis
by stimulating catabolic metabolism and suppressing anabolic pathways to increase
cellular energy levels. We found that the decrease in active phosphorylation of
AMPK in response to APAP correlates with decreased ATP levels, in vivo.
Therefore, we hypothesized that the enhanced production of ATP via AMPK
stimulation can lead to amelioration of APAP-induced liver failure. A769662, an
allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172
phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly,
activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in
C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally.
However, mice treated with APAP alone developed massive centrilobular necrosis,
and APAP increased their serum alanine aminotransferase and aspartate
aminotransferase levels. Furthermore, A769662 administration prevented the loss
of intracellular ATP without interfering with the APAP-mediated reduction of
mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy
glucose eliminated the beneficial effects of A769662 on APAP-mediated liver
injury. In conclusion, A769662 can effectively protect mice against APAP-induced
liver injury through ATP synthesis by anaerobic glycolysis. Furthermore,
stimulation of AMPK may have potential therapeutic application for APAP overdose.
PMID- 26434491
TI - Physiological Functions of the COPI Complex in Higher Plants.
AB - COPI vesicles are essential to the retrograde transport of proteins in the early
secretory pathway. The COPI coatomer complex consists of seven subunits, termed
alpha-, beta-, beta'-, gamma-, delta-, epsilon-, and zeta-COP, in yeast and
mammals. Plant genomes have homologs of these subunits, but the essentiality of
their cellular functions has hampered the functional characterization of the
subunit genes in plants. Here we have employed virus-induced gene silencing
(VIGS) and dexamethasone (DEX)-inducible RNAi of the COPI subunit genes to study
the in vivo functions of the COPI coatomer complex in plants. The beta'-, gamma-,
and delta-COP subunits localized to the Golgi as GFP-fusion proteins and
interacted with each other in the Golgi. Silencing of beta'-, gamma-, and delta
COP by VIGS resulted in growth arrest and acute plant death in Nicotiana
benthamiana, with the affected leaf cells exhibiting morphological markers of
programmed cell death. Depletion of the COPI subunits resulted in disruption of
the Golgi structure and accumulation of autolysosome-like structures in earlier
stages of gene silencing. In tobacco BY-2 cells, DEX-inducible RNAi of beta'-COP
caused aberrant cell plate formation during cytokinesis. Collectively, these
results suggest that COPI vesicles are essential to plant growth and survival by
maintaining the Golgi apparatus and modulating cell plate formation.
PMID- 26434494
TI - Blood Cadmium Level Associates with Lower Testosterone and Sex Hormone-Binding
Globulin in Chinese men: from SPECT-China Study, 2014.
AB - Cadmium is a widespread environmental pollutant. We aimed to determine whether
blood cadmium level (BCL) associates with reproductive hormones in a cross
sectional study. Our data were from SPECT-China. We selected 5690 participants
(2286 men and 3404 women), aged 18 years and older, among whom 1589 were
postmenopausal women. BCL, blood lead level, total testosterone (TT), estradiol
(E2), sex hormone-binding globulin (SHBG), luteinizing hormone, and follicle
stimulating hormone were measured. Results showed that BCL was significantly
higher in men (median 1.90 MUg/L) than that in women (median 1.56 MUg/L). The
median level of cadmium in postmenopausal women was 1.40 MUg/L. In men, BCL was
negatively correlated with TT (Spearmen coefficient = -0.057, P < 0.01) and SHBG
(Spearmen coefficient = -0.098, P < 0.01), but in postmenopausal women, this
correlation was not observed. In linear regression, after full adjustment for
blood lead level, age, body mass index, residence area, economic status, and
smoking, TT and SHBG were still negatively associated with BCL in men.
Additionally, the association between BCL and TT levels was modified by BMI group
(P for interaction = 0.041). However, from base model to fully adjusted model,
BCL was not associated with TT and E2 in postmenopausal women. In conclusion, men
had higher BCL than women in China, and BCL was associated with TT and SHBG in
Chinese men, which may have important implications for male reproductive health.
Concerted efforts are warranted to reduce adult cadmium exposure.
PMID- 26434495
TI - Temperature Management After Cardiac Arrest: An Advisory Statement by the
Advanced Life Support Task Force of the International Liaison Committee on
Resuscitation and the American Heart Association Emergency Cardiovascular Care
Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and
Resuscitation.
AB - For more than a decade, mild induced hypothermia (32 degrees C-34 degrees C)
has been standard of care for patients remaining comatose after resuscitation
from out-of-hospital cardiac arrest with an initial shockable rhythm, and this
has been extrapolated to survivors of cardiac arrest with initially nonshockable
rhythms and to patients with in-hospital cardiac arrest. Two randomized trials
published in 2002 reported a survival and neurological benefit with mild induced
hypothermia. One recent randomized trial reported similar outcomes in patients
treated with targeted temperature management at either 33 degrees C or 36
degrees C. In response to these new data, the International Liaison Committee on
Resuscitation Advanced Life Support Task Force performed a systematic review to
evaluate 3 key questions: (1) Should mild induced hypothermia (or some form of
targeted temperature management) be used in comatose post-cardiac arrest
patients? (2) If used, what is the ideal timing of the intervention? (3) If used,
what is the ideal duration of the intervention? The task force used Grading of
Recommendations Assessment, Development and Evaluation methodology to assess and
summarize the evidence and to provide a consensus on science statement and
treatment recommendations. The task force recommends targeted temperature
management for adults with out-of-hospital cardiac arrest with an initial
shockable rhythm at a constant temperature between 32 degrees C and 36 degrees
C for at least 24 hours. Similar suggestions are made for out-of-hospital cardiac
arrest with a nonshockable rhythm and in-hospital cardiac arrest. The task force
recommends against prehospital cooling with rapid infusion of large volumes of
cold intravenous fluid. Additional and specific recommendations are provided in
the document.
PMID- 26434496
TI - Australian general practitioner attitudes to clinical practice guidelines and
some implications for translating osteoarthritis care into practice.
AB - Clinical practice guidelines (CPGs) have been shown to improve processes of care
and health outcomes, but there is often a discrepancy between recommendations for
care and clinical practice. This study sought to explore general practitioner
(GP) attitudes towards CPGs, in general and specifically for osteoarthritis (OA),
with the implications for translating OA care into practice. A self-administered
questionnaire was conducted in January 2013 with a sample of 228 GPs in New South
Wales and South Australia. Seventy-nine GPs returned questionnaires (response
rate 35%). Nearly all GPs considered that CPGs support decision-making in
practice (94%) and medical education (92%). Very few respondents regarded CPGs as
a threat to clinical autonomy, and most recognised that individual patient
circumstances must be taken into account. Shorter CPG formats were preferred over
longer and more comprehensive formats, with preferences being evenly divided
among respondents for short, 2-3-page summaries, flowcharts or algorithms and
single page checklists. GPs considered accessibility to CPGs to be important, and
electronic formats were popular. Familiarity and use of The Royal Australian
College of General Practitioners OA Guideline was poor, with most respondents
either not aware of it (30%; 95% confidence interval (CI) 27 - 41%), had never
used it (19%; 95% CI 12 - 29%) or rarely used it (34%; 95% CI 25-45%). If CPGs
are to assist with the translation of evidence into practice, they must be easily
accessible and in a format that encourages use.
PMID- 26434497
TI - Relative Binding Free Energies of Adenine and Guanine to Damaged and Undamaged
DNA in Human DNA Polymerase eta: Clues for Fidelity and Overall Efficiency.
AB - Human DNA polymerase eta (Pol eta) plays an essential protective role against
skin cancer caused by cyclobutane thymine-thymine dimers (TTDs), a frequent form
of DNA damage arising from exposure to the sun. This enzyme rescues stalled
replication forks at the TTDs by inserting bases opposite these DNA defects.
Herein we calculate binding free energies for a free deoxyribose nucleotide
triphosphate, dATP or dGTP, to Pol eta complexed with undamaged or damaged DNA.
The calculations indicate that the binding of dATP to the enzyme-DNA complex is
thermodynamically favored for TTD-containing DNA over undamaged DNA, most likely
because of more extensive hydrogen-bonding interactions between the TTD and the
enzyme that hold the TTD more rigidly in place. The calculations also illustrate
that dATP binding is thermodynamically favored over dGTP binding at both thymine
positions of the TTD, most likely due to more persistent and stable hydrogen
bonding interactions between the TTD and dATP than between the TTD and dGTP. This
free energy difference is slightly greater for binding at the 5' thymine position
than at the 3' thymine position, presumably because of stabilization arising from
the A:T base pair formed at the 3' position of the TTD in the previous step of
Pol eta function. All of these trends in binding free energies are consistent
with experimental measurements of binding strength, fidelity, processivity, and
overall efficiency. The insights gained from this analysis have implications for
drug design efforts aimed at modifying the binding properties of this enzyme for
improving cancer chemotherapy treatments.
PMID- 26434498
TI - Core/Shell Face-Centered Tetragonal FePd/Pd Nanoparticles as an Efficient Non-Pt
Catalyst for the Oxygen Reduction Reaction.
AB - We report the synthesis of core/shell face-centered tetragonal (fct)-FePd/Pd
nanoparticles (NPs) via reductive annealing of core/shell Pd/Fe3O4 NPs followed
by temperature-controlled Fe etching in acetic acid. Among three different kinds
of core/shell FePd/Pd NPs studied (FePd core at ~8 nm and Pd shell at 0.27, 0.65,
or 0.81 nm), the fct-FePd/Pd-0.65 NPs are the most efficient catalyst for the
oxygen reduction reaction (ORR) in 0.1 M HClO4 with Pt-like activity and
durability. This enhanced ORR catalysis arises from the desired Pd lattice
compression in the 0.65 nm Pd shell induced by the fct-FePd core. Our study
offers a general approach to enhance Pd catalysis in acid for ORR.
PMID- 26434499
TI - Gesture, sign, and language: The coming of age of sign language and gesture
studies.
AB - How does sign language compare with gesture, on the one hand, and spoken language
on the other? Sign was once viewed as nothing more than a system of pictorial
gestures without linguistic structure. More recently, researchers have argued
that sign is no different from spoken language, with all of the same linguistic
structures. The pendulum is currently swinging back toward the view that sign is
gestural, or at least has gestural components. The goal of this review is to
elucidate the relationships among sign language, gesture, and spoken language. We
do so by taking a close look not only at how sign has been studied over the past
50 years, but also at how the spontaneous gestures that accompany speech have
been studied. We conclude that signers gesture just as speakers do. Both produce
imagistic gestures along with more categorical signs or words. Because at present
it is difficult to tell where sign stops and gesture begins, we suggest that sign
should not be compared with speech alone but should be compared with speech-plus
gesture. Although it might be easier (and, in some cases, preferable) to blur the
distinction between sign and gesture, we argue that distinguishing between sign
(or speech) and gesture is essential to predict certain types of learning and
allows us to understand the conditions under which gesture takes on properties of
sign, and speech takes on properties of gesture. We end by calling for new
technology that may help us better calibrate the borders between sign and
gesture.
PMID- 26434500
TI - Effect of Intestinal Tapeworm Clestobothrium crassiceps on Concentrations of
Toxic Elements and Selenium in European Hake Merluccius merluccius from the Gulf
of Lion (Northwestern Mediterranean Sea).
AB - The capacity for heavy metal bioaccumulation by some fish parasites has been
demonstrated, and their contribution to decreasing metal concentrations in
tissues of parasitized fish has been hypothesized. The present study evaluated
the effect of the cestode Clestobothrium crassiceps on the accumulation of trace
elements in 30 European hake, Merluccius merluccius, in Spain (half of them
infested by C. crassiceps). Tissue samples from all M. merluccius and specimens
of C. crassiceps from the infected hakes were collected and stored until element
analysis by inductively coupled plasma mass spectrometry (ICP-MS). Arsenic,
mercury, and selenium were generally present in lower levels in the cestode than
in all hake tissues. The mean value of the muscular Se:Hg molar ratio in the
infested subsample was higher than that in hakes without cestodes. Values
indicate that the edible part of infested hakes presents a lower amount of Cd and
Pb in relation to noninfested hakes.
PMID- 26434501
TI - Relative validity and reproducibility of a parent-administered semi-quantitative
FFQ for assessing food intake in Danish children aged 3-9 years.
AB - OBJECTIVE: To assess the relative validity and reproducibility of the semi
quantitative FFQ (SFFQ) applied in the evaluation of a community intervention
study, SoL-Bornholm, for estimating food intakes. DESIGN: The reference measure
was a 4 d estimated food record. The SFFQ was completed two times separated by a
1-month period in order to test reproducibility. SETTING: The Capital Region and
the Regional Municipality of Bornholm, Denmark. SUBJECTS: A total of fifty-four
children aged 3-9 years were enrolled in the study. RESULTS: In terms of
validity, the SFFQ generally overestimated intakes compared with the food
records, especially for vegetables. For most intakes, the mean difference
increased with increasing intake. Gross misclassification was on average higher
for energy and nutrients (17%) than for foods (8%). Spearman correlation
coefficients were significant for twelve out of fourteen intakes, ranging from
0.29 to 0.63 for foods and from 0.12 to 0.48 for energy and nutrients. Comparing
the repeated SFFQ administrations, the intakes of the first SFFQ were slightly
higher than those of the second SFFQ. Gross misclassification was low for most
intakes; on average 6% for foods and 8% for energy and nutrients. Intra-class
correlations were significant for all intakes, ranging from 0.30 to 0.82 for
foods and from 0.46 to 0.81 for energy and nutrients. CONCLUSIONS: The results
indicate that the SFFQ gives reproducible estimates. The relative validity of the
SFFQ was low to moderate for most intakes but comparable to other studies among
children.
PMID- 26434502
TI - Mitofusin 2 ameliorates hypoxia-induced apoptosis via mitochondrial function and
signaling pathways.
AB - Mitochondrial dynamics play a critical role in mitochondrial function and
signaling. Although mitochondria play a critical role in hypoxia/ischemia, the
further mechanisms between mitochondrial dynamics and ischemia are still unclear.
The current study aimed to determine the role of mitofusin 2, a key regulator of
mitochondrial fusion, in a hypoxic model and to explore a novel strategy for
cerebral ischemia via modulation of mitochondrial dynamics. To the best of our
knowledge, this is the first study to investigate both mitochondrial function and
molecular pathways to determine the role of mitofusin 2 in hypoxia-induced
neuronal apoptosis. In vivo, C57BL/6 mice (male, 19-25g) underwent a permanent
middle cerebral artery occlusion for 12 or 24h (n=6 per group). In vitro, cobalt
chloride was used to mimic hypoxia in immortalized hippocampal neurons. Down- or
up-regulation of Mfn2 was induced to investigate the role of Mfn2 in hypoxia,
especially in mitochondrial function and signaling pathways. The findings
demonstrated that decreased mitofusin 2 occurred both in vivo and in vitro
hypoxic models; second, the anti-apoptotic effect of Mfn2 may work via
restoration of mitochondrial function; third, the modulation of the B Cell
Leukemia 2/Bcl-2 Associated X protein and extracellular signal-regulated kinase
1/2 signaling pathways highlight the role of Mfn2 in signaling pathways beyond
fusion. In summary, depletion of mitofusin 2 would lead to apoptosis both in
normal or hypoxic conditions; however, mitofusin 2 overexpression could attenuate
hypoxia-induced apoptosis, which represents a potential novel strategy for
neuroprotection against ischemic brain damage.
PMID- 26434503
TI - Conventional protein kinase C isoforms differentially regulate ADP- and thrombin
evoked Ca2+ signalling in human platelets.
AB - Rises in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) are central in platelet
activation, yet many aspects of the underlying mechanisms are poorly understood.
Most studies examine how experimental manipulations affect agonist-evoked rises
in [Ca(2+)]cyt, but these only monitor the net effect of manipulations on the
processes controlling [Ca(2+)]cyt (Ca(2+) buffering, sequestration, release,
entry and removal), and cannot resolve the source of the Ca(2+) or the
transporters or channels affected. To investigate the effects of protein kinase C
(PKC) on platelet Ca(2+) signalling, we here monitor Ca(2+) flux around the
platelet by measuring net Ca(2+) fluxes to or from the extracellular space and
the intracellular Ca(2+) stores, which act as the major sources and sinks for
Ca(2+) influx into and efflux from the cytosol, as well as monitoring the
cytosolic Na(+) concentration ([Na(+)]cyt), which influences platelet Ca(2+)
fluxes via Na(+)/Ca(2+) exchange. The intracellular store Ca(2+) concentration
([Ca(2+)]st) was monitored using Fluo-5N, the extracellular Ca(2+) concentration
([Ca(2+)]ext) was monitored using Fluo-4 whilst [Ca(2+)]cyt and [Na(+)]cyt were
monitored using Fura-2 and SFBI, respectively. PKC inhibition using Ro-31-8220 or
bisindolylmaleimide I potentiated ADP- and thrombin-evoked rises in [Ca(2+)]cyt
in the absence of extracellular Ca(2+). PKC inhibition potentiated ADP-evoked but
reduced thrombin-evoked intracellular Ca(2+) release and Ca(2+) removal into the
extracellular medium. SERCA inhibition using thapsigargin and 2,5-di(tert-butyl)
l,4-benzohydroquinone abolished the effect of PKC inhibitors on ADP-evoked
changes in [Ca(2+)]cyt but only reduced the effect on thrombin-evoked responses.
Thrombin evokes substantial rises in [Na(+)]cyt which would be expected to reduce
Ca(2+) removal via the Na(+)/Ca(2+) exchanger (NCX). Thrombin-evoked rises in
[Na(+)]cyt were potentiated by PKC inhibition, an effect which was not due to
altered changes in non-selective cation permeability of the plasma membrane as
assessed by Mn(2+) quench of Fura-2 fluorescence. PKC inhibition was without
effect on thrombin-evoked rises in [Ca(2+)]cyt following SERCA inhibition and
either removal of extracellular Na(+) or inhibition of Na(+)/K(+)-ATPase activity
by removal of extracellular K(+) or treatment with digoxin. These data suggest
that PKC limits ADP-evoked rises in [Ca(2+)]cyt by acceleration of SERCA
activity, whilst rises in [Ca(2+)]cyt evoked by the stronger platelet activator
thrombin are limited by PKC through acceleration of both SERCA and Na(+)/K(+)
ATPase activity, with the latter limiting the effect of thrombin on rises in
[Na(+)]cyt and so forward mode NCX activity. The use of selective PKC inhibitors
indicated that conventional and not novel PKC isoforms are responsible for the
inhibition of agonist-evoked Ca(2+) signalling.
PMID- 26434504
TI - A scoring system to predict the severity of appendicitis in children.
AB - BACKGROUND: It appears that two forms of appendicitis exist. Preoperative
distinction between the two is essential to optimize treatment outcome. This
study aimed to develop a scoring system to accurately determine the severity of
appendicitis in children. MATERIALS AND METHODS: Historical cohort study of
pediatric patients (aged 0-17 y old) with appendicitis treated between January
2010 and December 2012. Division into simple, complex appendicitis, or another
condition based on preset criteria. Multiple logistic regression analysis was
used to build the prediction model with subsequent validation. RESULTS: There
were 64 patients with simple and 66 with complex appendicitis. Five variables
explained 64% of the variation. Independent validation of the derived prediction
model in a second cohort (55 simple and 10 complex appendicitis patients)
demonstrated 90% sensitivity (54-99), 91% specificity (79-97), a positive
predictive value of 64% (36-86), and an negative predictive value of 98% (88
100). The likelihood ratio+ was 10 (4.19-23.42), and likelihood ratio- was 0.11
(0.02-0.71). Diagnostic accuracy was 91% (84-98). CONCLUSIONS: Our scoring system
consisting of five variables can be used to exclude complex appendicitis in
clinical practice if the score is <4.
PMID- 26434505
TI - Inhibition of peptidylarginine deiminase attenuates inflammation and improves
survival in a rat model of hemorrhagic shock.
AB - BACKGROUND: We have recently shown that inhibition of peptidylarginine deiminase
(PAD) improves survival in a rodent model of lethal cecal ligation and puncture.
The roles of PAD inhibitors in hemorrhagic shock (HS), however, are largely
unknown. The goal of this study was to investigate the effects of YW3-56, a novel
PAD inhibitor, on survival after severe HS. METHODS: Mouse macrophages were
exposed to hypoxic conditions followed by reoxygenation in the presence or
absence of YW3-56. Enzyme-linked immunosorbent assay (ELISA) was performed to
measure levels of secreted tumor necrosis factor alpha and interleukin-6 in the
culture medium. Cell viability was determined by methyl thiazolyl tetrazolium
assay. In the survival experiment, anesthetized male Wistar-Kyoto rats (n =
10/group) were subjected to 55% blood loss, and treated with or without YW3-56
(10 mg/kg, intraperitoneally). Survival was monitored for 12 h. In the
nonsurvival experiment, morphologic changes of the lungs were examined. Levels of
circulating cytokine-induced neutrophil chemoattractant 1 (CINC-1) and
myeloperoxidase (MPO) in the lungs were measured by ELISA. Expression of lung
intercellular adhesion molecules-1 (ICAM-1) was also determined by Western
blotting. RESULTS: Hypoxia/reoxygenation (H/R) insult induced tumor necrosis
factor alpha and interleukin-6 secretion from macrophages, which was
significantly attenuated by YW3-56 treatment. YW3-56 treatment also increased
cell viability when macrophages were exposed to H/R up to 6/15 h and improved
survival rate from 20% to 60% in lethal HS rat model. Compared to the sham
groups, pulmonary MPO activity and ICAM-1 expression in the HS group were
significantly increased, and acute lung injury was associated with a higher
degree of CINC-1 levels in serum. Intraperitoneal delivery of YW3-56
significantly reduced pulmonary MPO and ICAM-1 expression and attenuated acute
lung injury. CONCLUSIONS: Our results demonstrate for the first time that
administration of YW3-56, a novel PAD inhibitor, can improve survival in a rat
model of HS and in a cell culture model of H/R. The survival advantage is
associated with an attenuation of local and systemic pro-inflammatory cytokines
and the protection against acute lung injury after hemorrhage. Thus, PAD
inhibition may represent a novel and promising therapeutic strategy for severe
HS.
PMID- 26434506
TI - Sequence-Structure-Function Classification of a Catalytically Diverse
Oxidoreductase Superfamily in Mycobacteria.
AB - The deazaflavin cofactor F420 enhances the persistence of mycobacteria during
hypoxia, oxidative stress, and antibiotic treatment. However, the identities and
functions of the mycobacterial enzymes that utilize F420 under these conditions
have yet to be resolved. In this work, we used sequence similarity networks to
analyze the distribution of the largest F420-dependent protein family in
mycobacteria. We show that these enzymes are part of a larger split beta-barrel
enzyme superfamily (flavin/deazaflavin oxidoreductases, FDORs) that include
previously characterized pyridoxamine/pyridoxine-5'-phosphate oxidases and heme
oxygenases. We show that these proteins variously utilize F420, flavin
mononucleotide, flavin adenine dinucleotide, and heme cofactors. Functional
annotation using phylogenetic, structural, and spectroscopic methods revealed
their involvement in heme degradation, biliverdin reduction, fatty acid
modification, and quinone reduction. Four novel crystal structures show that
plasticity in substrate binding pockets and modifications to cofactor binding
motifs enabled FDORs to carry out a variety of functions. This systematic
classification and analysis provides a framework for further functional analysis
of the roles of FDORs in mycobacterial pathogenesis and persistence.
PMID- 26434507
TI - Bacterial danger sensing.
AB - Here we propose that bacteria detect and respond to threats posed by other
bacteria via an innate immune-like process that we term danger sensing. We find
support for this contention by reexamining existing literature from the
perspective that intermicrobial antagonism, not opportunistic pathogenesis, is
the major evolutionary force shaping the defensive behaviors of most bacteria. We
conclude that many bacteria possess danger sensing pathways composed of a danger
signal receptor and corresponding signal transduction mechanism that regulate
pathways important for survival in the presence of the perceived competitor.
PMID- 26434508
TI - ExoCarta: A Web-Based Compendium of Exosomal Cargo.
AB - Exosomes are membranous vesicles that are released by a variety of cells into the
extracellular microenvironment and are implicated in intercellular communication.
As exosomes contain RNA, proteins and lipids, there is a significant interest in
characterizing the molecular cargo of exosomes. Here, we describe ExoCarta
(http://www.exocarta.org), a manually curated Web-based compendium of exosomal
proteins, RNAs and lipids. Since its inception, the database has been highly
accessed (>54,000 visitors from 135 countries). The current version of ExoCarta
hosts 41,860 proteins, >7540 RNA and 1116 lipid molecules from more than 286
exosomal studies annotated with International Society for Extracellular Vesicles
minimal experimental requirements for definition of extracellular vesicles.
Besides, ExoCarta features dynamic protein-protein interaction networks and
biological pathways of exosomal proteins. Users can download most often
identified exosomal proteins based on the number of studies. The downloaded files
can further be imported directly into FunRich (http://www.funrich.org) tool for
additional functional enrichment and interaction network analysis.
PMID- 26434509
TI - Nucleocytoplasmic Transport of RNAs and RNA-Protein Complexes.
AB - RNAs and ribonucleoprotein complexes (RNPs) play key roles in mediating and
regulating gene expression. In eukaryotes, most RNAs are transcribed, processed
and assembled with proteins in the nucleus and then either function in the
cytoplasm or also undergo a cytoplasmic phase in their biogenesis. This
compartmentalization ensures that sequential steps in gene expression and RNP
production are performed in the correct order and it allows important quality
control mechanisms that prevent the involvement of aberrant RNAs/RNPs in these
cellular pathways. The selective exchange of RNAs/RNPs between the nucleus and
cytoplasm is enabled by nuclear pore complexes, which function as gateways
between these compartments. RNA/RNP transport is facilitated by a range of
nuclear transport receptors and adaptors, which are specifically recruited to
their cargos and mediate interactions with nucleoporins to allow directional
translocation through nuclear pore complexes. While some transport factors are
only responsible for the export/import of a certain class of RNA/RNP, others are
multifunctional and, in the case of large RNPs, several export factors appear to
work together to bring about export. Recent structural studies have revealed
aspects of the mechanisms employed by transport receptors to enable specific
cargo recognition, and genome-wide approaches have provided the first insights
into the diverse composition of pre-mRNPs during export. Furthermore, the
regulation of RNA/RNP export is emerging as an important means to modulate gene
expression under stress conditions and in disease.
PMID- 26434510
TI - Myths to Debunk to Improve Management, Referral, and Outcomes in Patients With
Chronic Total Occlusion of an Epicardial Coronary Artery.
AB - A chronic total occlusion (CTO) is defined as an occlusive (100% stenosis)
coronary lesion with anterograde Thrombolysis In Myocardial Infarction 0 flow for
at least 3 months. CTOs are common in patients referred for coronary angiography
(up to 33%) and are associated with angina, impaired quality of life, and reduced
survival. Unfortunately, CTO percutaneous coronary intervention continues to be
underperformed worldwide (10% to 15% at most institutions, ~30% where expert
operators are available). The aim of this study was to address common fallacies
pertaining to CTOs among cardiologists by providing a concise review of pertinent
previously published reports along with an update on safety and efficacy of state
of-the-art CTO percutaneous coronary intervention techniques.
PMID- 26434511
TI - Identification by ultrasound evaluation of the carotid and femoral arteries of
high-risk subjects missed by three validated cardiovascular disease risk
algorithms.
AB - Atherosclerotic cardiovascular disease (ASCVD) events are the leading cause of
death in the United States and globally. Traditional global risk algorithms may
miss 50% of patients who experience ASCVD events. Noninvasive ultrasound
evaluation of the carotid and femoral arteries can identify subjects at high risk
for ASCVD events. We examined the ability of different global risk algorithms to
identify subjects with femoral and/or carotid plaques found by ultrasound. The
study population consisted of 1,464 asymptomatic adults (39.8% women) aged 23 to
87 years without previous evidence of ASCVD who had ultrasound evaluation of the
carotid and femoral arteries. Three ASCVD risk algorithms (10-year Framingham
Risk Score [FRS], 30-year FRS, and lifetime risk) were compared for the 939
subjects who met the algorithm age criteria. The frequency of femoral plaque as
the only plaque was 18.3% in the total group and 14.8% in the risk algorithm
groups (n = 939) without a significant difference between genders in frequency of
femoral plaque as the only plaque. Those identified as high risk by the lifetime
risk algorithm included the most men and women who had plaques either femoral or
carotid (59% and 55%) but had lower specificity because the proportion of
subjects who actually had plaques in the high-risk group was lower (50% and 35%)
than in those at high risk defined by the FRS algorithms. In conclusion,
ultrasound evaluation of the carotid and femoral arteries can identify subjects
at risk of ASCVD events missed by traditional risk-predicting algorithms. The
large proportion of subjects with femoral plaque only supports the use of
including both femoral and carotid arteries in ultrasound evaluation.
PMID- 26434512
TI - Mechanical circulatory support devices and transcatheter aortic valve
implantation (from the National Inpatient Sample).
AB - High-risk surgical patients undergoing transcatheter aortic valve implantation
(TAVI) represent an emerging population, which may benefit from short-term use of
mechanical circulatory support (MCS) devices. The aim of this study was to
determine the practice and inhospital outcomes of MCS utilization in patients
undergoing TAVI. We analyzed data from Nationwide Inpatient Sample (2011 and
2012) using the International Classification of Diseases, Ninth Revision,
Clinical Modification procedure codes. A total of 1,794 TAVI procedures (375
hospitals in the United States) were identified of which 190 (10.6%) used an MCS
device (MCS group) and 1,604 (89.4%) did not (non-MCS group). The use of MCS
devices with TAVI was associated with significant increase in the inhospital
mortality (14.9% vs 3.5%, p <0.01). The mean length (11.8 +/- 0.8 vs 8.1 +/- 0.2
days, p <0.01) and cost ($68,997 +/- 3,656 vs $55,878 +/- 653, p = 0.03) of
hospitalization were also significantly greater in the MCS group. Ventricular
fibrillation arrest, transapical access for TAVI, and cardiogenic shock were the
most significant predictors of MCS use during TAVI. In the multivariate model,
use of any MCS device was found to be an independent predictor of increased
mortality (odds ratio 3.5, 95% confidence interval 2.6 to 4.6, p <0.0001) and
complications (odds ratio 3.3, 95% confidence interval 2.8 to 3.9, p <0.0001).
The propensity score-matched analysis also showed a similar result. In
conclusion, the unacceptably high rates of mortality and complications coupled
with a significant increase in the length and cost of hospitalization should
raise concerns about utility of MCS devices during TAVI in this prohibitive
surgical risk population.
PMID- 26434513
TI - Impact of an Empiric Isolation of the Superior Vena Cava in Addition to
Circumferential Pulmonary Vein Isolation on the Outcome of Paroxysmal Atrial
Fibrillation Ablation.
AB - The safety and efficacy of an empiric superior vena cava isolation (SVCI) in
addition to circumferential pulmonary vein isolation (CPVI) in patients with
paroxysmal atrial fibrillation (PAF) have not been clarified. A total of 186
consecutive patients who underwent catheter ablation of PAF were included. All
patients underwent a CPVI. Patients in the first half underwent an additional
SVCI only if SVC-triggered AF or rapid SVC activity was observed during the
procedure (n = 93, as-needed SVCI, group I), and those in the second half
underwent an empirical SVCI after the CPVI (n = 93, empiric SVCI, group II). The
CPVI was successfully performed in all patients. An SVCI was performed in 8 of 93
patients (9%) in group I and 81 of the 93 patients (87%) in group II. In the
remaining 12 patients in group II, an SVCI was not performed because of the lack
of SVC potentials. During a mean follow-up of 27 +/- 12 months, the atrial
tachyarrhythmia recurrence rate after a single ablation procedure in the patients
in group II was lower than that in group I (44% vs 23%, p = 0.035). A Cox
regression multivariate analysis demonstrated that an empiric SVCI was an
independent predictor of an atrial tachyarrhythmia recurrence after a single
ablation procedure (odds ratio: 0.57, 95% confidence interval 0.31 to 0.999; p =
0.049). Neither sinus node injury nor any injury to the phrenic nerve was
observed. In conclusion, an empiric SVCI in addition to the CPVI improved the
outcome of AF ablation in patients with PAF without any additional adverse
effects.
PMID- 26434514
TI - Significance and Determinants of Cardiac Troponin I in Patients With Obstructive
Hypertrophic Cardiomyopathy.
AB - Serum cardiac troponins have been demonstrated to have important clinical
implications in patients with hypertrophic cardiomyopathy (HC). However, little
is known about their roles in patients with obstructive HC. The aim of this study
was to explore the clinical significance and determinants of serum cardiac
troponin I (cTnI) in patients with obstructive HC using cardiovascular magnetic
resonance imaging. We investigated the relations between serum cTnI levels and
clinical, echocardiographic, and cardiovascular magnetic resonance parameters and
assessed the determinants of serum cTnI in 149 consecutive patients with
obstructive HC. The median level of serum cTnI was 0.019 ng/ml (interquartile
range 0.009 to 0.044). CTnI was elevated (>=0.04 ng/ml) in 42 (28%) of the
overall cohort. Patients with elevated cTnI had greater maximum wall thickness (p
<0.001), larger left ventricular mass index (LVMI, p <0.001), more frequency of
left atrium diameter >=50 mm (p = 0.020), higher plasma values of N-terminal pro
B-type natriuretic peptide (p <0.001), and less hypertension (p = 0.014). Serum
cTnI levels were positively correlated with maximum wall thickness (r = 0.444, p
<0.001), LVMI (r = 0.556, p <0.001), N-terminal pro-B-type natriuretic peptide (r
= 0.305, p <0.001), left ventricular end-diastolic volume index (r = 0.246, p =
0.002), and left ventricular end-systolic volume index (r = 0.272, p = 0.001) but
negatively with left ventricular ejection fraction (r = -0.180, p = 0.028). On
multivariate analysis, LVMI was independently associated with both elevated cTnI
(odds ratio 1.032, p = 0.001) and increasing serum cTnI levels (beta = 0.556, p
<0.001). In addition, the presence of hypertension was independently related to
less likely elevated cTnI (odds ratio 0.307, p = 0.029) and decreasing levels of
serum cTnI (beta = -0.165, p = 0.015). In conclusion, levels of serum cTnI are
elevated in a significant proportion of our patients. Serum cTnI is associated
with multiple parameters of disease severity, suggesting its great significance
in assessing cardiac remodeling in patients with obstructive HC. Left ventricular
hypertrophy, as indicated by LVMI, is the major determinant of serum cTnI levels.
PMID- 26434515
TI - Relation Between Monocyte to High-Density Lipoprotein Cholesterol Ratio With
Presence and Severity of Isolated Coronary Artery Ectasia.
AB - The aim of this study was to investigate an easily available inflammatory and
oxidative stress marker and monocyte to high-density lipoprotein cholesterol
ratio (MHR) in patients with coronary artery ectasia (CAE). The study population
included 405 patients of which 135 patients had isolated CAE, 135 patients had
obstructive coronary artery disease (CAD), and 135 patients had normal coronary
angiograms (NCAs). The severity of isolated CAE was determined according to the
Markis classification. The MHR was significantly greater in patients with
isolated CAE than those with obstructive CAD and NCAs: 14.8 (11.6 to 19.8), 11.4
(9.6 to 13.5), 9.8 (7.5 to 11.9), respectively. Linear regression analyses showed
that MHR and C-reactive protein were significantly related with the severity of
isolated CAE. In conclusion, the MHR is significantly greater in patients with
CAE compared to controls with obstructive CAD and NCAs, and MHR is associated
with the severity of CAE.
PMID- 26434516
TI - Stroke Risk Factors Beyond the CHA2DS2-VASc Score: Can We Improve Our
Identification of "High Stroke Risk" Patients With Atrial Fibrillation?
AB - The prevention of stroke and other thromboembolic events plays a crucial role in
the management of patients with atrial fibrillation. Not all patients with atrial
fibrillation are equal in terms of thromboembolic risk; therefore, not all will
benefit from oral anticoagulation treatment. The general principle is that the
expected benefit of anticoagulation in reduction of thromboembolic risk must
exceed the expected harm caused by possible bleeding. Some guidelines have
focused on a categorical approach to stroke prevention, with a focus on
identifying patients at high risk for oral anticoagulation. Various current
guidelines recommend assessment of stroke risk using the CHADS2 or CHA2DS2-VASc
scores to initially detect patients at low risk who require no antithrombotic
therapy. However, the scores do not incorporate all possible risk factors causing
a high thromboembolic risk. Factors such as impaired renal function, obstructive
sleep apnea, and echocardiographic and biochemical or coagulation parameters can
also predict adverse thromboembolic events. The present review aims to describe
biomarkers whether blood, urine, imaging (cardiac or cerebral), or clinical that
go beyond the CHA2DS2-VASc score and potentially aid stroke risk assessment.
Although useful in some cases, the presented parameters should be perhaps used to
further refine initial identification of patients at low risk, after which
effective stroke prevention can be offered to those with >=1 additional stroke
risk factors.
PMID- 26434517
TI - Protective effect of Astragalus polysaccharide on endothelial progenitor cells
injured by thrombin.
AB - Several studies have demonstrated that Astragalus polysaccharide (APS) has a
protective effect on endothelial cells damaged by various factors. To examine the
role of APS in the endothelial inflammatory response, rat bone marrow endothelial
progenitor cells (EPCs) were isolated by density gradient centrifugation and
identified by immunohistochemistry, then we established a model of inflammatory
injury induced by thrombin and measured the effects of APS on EPC viability and
proliferation by MTT assays. We also assayed the effect APS had on the
inflammatory response, by examining the nuclear factor kappa B (NF-kappaB)
signaling pathway, as well as the expression of intercellular adhesion molecule-1
(ICAM-1), vascular endothelial growth factor (VEGF) and its receptors Flt-1 and
KDR. Results demonstrated that EPCs were damaged by thrombin, and APS appeared to
inhibit this damage. APS suppressed thrombin-induced ICAM-1 expression by
blocking NF-kappaB signaling in rat bone marrow EPCs, and up-regulating
expression of VEGF and its receptors. We believed that APS may be used to treat
and prevent EPC injury-related diseases.
PMID- 26434518
TI - Hydrogen peroxide sensing and cytotoxicity activity of Acacia lignin stabilized
silver nanoparticles.
AB - The study is aimed at detection of hydrogen peroxide (H2O2) using Acacia lignin
mediated silver nanoparticles (AGNPs). The synthesis of AGNPs was achieved at
conditions optimized as, 3 ml of 0.02% lignin and 1mM silver nitrate incubated
for 30 min at 80 degrees C and pH 9. Initial screening of AGNPs was performed by
measuring the surface plasmon resonance peak at 410-430 nm using UV-vis
spectrophotometer. Transmission electron microscopy, atomic force microscopy, X
ray diffraction and particle size analysis confirmed the spherical shaped face
centered cubic structure and 10-50 nm size of AGNPs. The infrared spectroscopy
study further revealed that the active functional groups present in lignin were
responsible for the reduction of silver ions (Ag(+)) to metallic silver (Ag(0)).
Lignin stabilized silver nanoparticles showed good sensitivity and a linear
response over wide concentrations of H2O2 (10(-1) to 10(-6)M). Further, the in
vitrocytotoxicity activity of the lignin mediated AGNPs (5-500 MUg/ml)
demonstrated toxicity effects in MCF-7 and A375 cell lines. Thus, lignin
stabilized silver nanoparticles based optical sensor for H2O2 could be
potentially applied in the determination of reactive oxygen species and toxic
chemicals which further expands the importance of lignin stabilized silver
nanoparticles.
PMID- 26434519
TI - Covalent immobilization of Enterococcus faecalis Esawy dextransucrase and dextran
synthesis.
AB - Enterococcus faecalis Esawy dextransucrase was immobilized in Fe(3+)-cross-linked
alginate/carboxymethyl cellulose (AC) beads. The gel beads were modified with
polyethylenimine (PEI) followed by glutaraldehyde (GA) to form Fe(3+) (ACPG)
beads. Fe(3+) (ACPG) was characterized using FTIR and DSC techniques. GA
activated beads showed new two peaks. The first was at 1,717 cm(-1) which refers
to (CO) group of a free aldehyde end of glutaraldehyde, and another peak was at
1,660 cm(-1) referring to (CN) group. The immobilization process improved the
optimum temperature from 35 to 45 degrees C. The immobilized enzyme showed its
optimum activity in wide pH range (4.5-5.4) compared to pH 5.4 in case of free
form. Also, the immobilization process improved the thermal and pH enzyme
stability to great extent. Reusability test proved that the enzyme activity
retained 60% after 15 batch reactions. Immobilized enzyme was applied
successfully in the synthesis of oligosaccharides and different molecular weights
of dextran.
PMID- 26434520
TI - Some physico-chemical properties of Prunus armeniaca L. gum exudates.
AB - The objectives of this paper were to investigate some physicochemical properties
of Prunus armeniaca L. gum exudates (PAGE). PAGE had, on average, 66.89%
carbohydrate, 10.47% uronic acids, 6.9% moisture (w.b.), 2.91% protein, 4% ash
and 1.59% fat. PAGE was composed of monosaccharides including l-arabinose, d
galactose, xylose, mannose and rhamnose in molar percentages of 41.52%, 23.72%,
17.82%, 14.40% and 2.54%, respectively. Elemental analysis showed that PAGE had
high values of nutrients. FTIR analysis demonstrated the presence of carboxyl,
hydroxyl and methyl groups and glycoside bonds. The weight average molecular
weight, number average molecular weight and polydispersity index were found to be
approximately 5.69 * 10(5)g/mol, 4.33 g/mol and 1.31, respectively. Rheological
measurement of PAGE solutions as a function of concentration (8, 10 and 12%
(w/w)) and temperature (10, 20, 30 and 40 degrees C) demonstrated that the gum
solutions had a non Newtonian shear thinning behaviour. Intrinsic viscosity for
PAGE in deionized water was 3.438 dl/g based on Kramer equation.
PMID- 26434521
TI - Evaluation of selected properties of biocompatible chitosan/poly(vinyl alcohol)
blends.
AB - Selected properties of chitosan (CS) and poly(vinyl alcohol) (PVA) blends
crosslinked by tetraethoxysilane (TEOS) were studied. XRD analysis showed
characteristics peak at 22.5 degrees attributed to the crystalline structure of
CS and PVA. DSC thermograms unveiled the quantitative determination of free,
intermediate and bound water in the blends. Tensile strength and fracture strain
of blends were observed due to the combined effect of physically and chemically
crosslinked network structures. The decrease in water contact angle indorsed the
hydrophilic performance while the storage modulus G' and loss modulus G" was
decreased as the temperature was increased exhibited the viscoelastic property of
the blends. The fabricated blends can be employed for drug delivery systems,
tissue engineering and other biomedical applications.
PMID- 26434522
TI - Production of pullulan from raw potato starch hydrolysates by a new strain of
Auerobasidium pullulans.
AB - In the present study, hydrolysis of potato starch with marine cold-adapted alpha
amylase and pullulan production from the hydrolysates by a new strain of
Auerobasidium pullulans isolated from sea mud were conducted. The hydrolysis
conditions were optimized as follows: reaction time 2h, pH 6.5, temperature 20
degrees C, and alpha-amylase amount 12 U/g. Under these optimum hydrolysis
conditions, the DE value of the potato starch hydrolysates reached to 49.56. The
potato starch hydrolysates consist of glucose, maltose, isomaltose, maltotriose,
and trace of other maltooligosaccharides with degree of polymerization ranged 4
7. The maximum production of pullulan at 96 h from the hydrolysate of potato
starch was 36.17 g/L, which was higher than those obtained from glucose (22.07
g/L, p<0.05) and sucrose (31.42 g/L, p<0.05). Analysis of the high performance
liquid chromatography of the hydrolysates of the pullulan product with
pullulanase indicated that the main composition is maltotriose, thus confirming
the pullulan structure of this pullulan product.
PMID- 26434523
TI - Silver nanoparticle synthesis using lignin as reducing and capping agents: A
kinetic and mechanistic study.
AB - Silver nanoparticles (AgNPs) were robustly synthesized from aqueous AgNO3 with
alkali lignin (low sulfonate) (ALls) severing as dual reducing and capping agent.
The AgNP synthesis mechanisms were highly pH dependent. Under neutral and acidic
conditions, polydispersed AgNPs were synthesized via the self-catalyzed reduction
of Ag(+) on instantaneously formed Ag2O surfaces followed by the slower pseudo
first order reduction. The Ag2O nanoparticles functioned as the nucleating sites
for the reduction of remaining silver cations to form AgNPs whose size and size
distribution strongly dependent of lignin concentrations. AgNPs were optimally
synthesized by reducing 2 mmol/L AgNO3 with 0.16 wt% ALls at pH 10 and 85 degrees
C in 30 min to near 100% yield in bimodal distributed sizes with 23% and 77% in
feret diameters of 7.3 (+/- 2.2)nm and 14.3 (+/- 1.8)nm, respectively.
PMID- 26434524
TI - Synthesis of nanohydrogels based on tragacanth gum biopolymer and investigation
of swelling and drug delivery.
AB - The present article deals with preparation of pH responsive nanohydrogels based
on tragacanth gum (TG) biopolymer for drug delivery. The nanohydrogels were
prepared using different chemical reagents such as 3-aminopropyltriethoxysilane
(APTES) modifier and glyceroldiglycidylether (GDE), polyvinyl alcohol (PVA), and
glutaraldehyde (GA) as cross-linkers. The obtained nanohydrogels were
characterized using different techniques such as scanning electron microscope
(SEM), elemental analysis, FT-IR, zeta sizer and thermogravimetric analysis
(TGA). The gel content increased with increasing the cross-linkers contents and
reached to a maximum of 90%. The swelling behavior of nanohydrogels was
investigated in terms of the effect of pH (2.2, 7.4 and 9), temperature (27, 37
and 60 degrees C), and reaction time (2-24h). Loading of Indomethacin (IND) as a
model drug showed dependence on the network structure of nanohydrogels. The total
in vitro IND release showed dependence on the network structure of nanohydrogels
and was in the range of 50-80% at pH 9 after 24h.
PMID- 26434525
TI - Removal of copper(II) from aqueous solution using nanochitosan/sodium
alginate/microcrystalline cellulose beads.
AB - The present study was aimed to prepare the novel ternary biopolymeric beads of
nanochitosan (NCS)/sodium alginate (SA)/microcrystalline cellulose (MC) for the
removal of heavy metal copper from aqueous solution through batch adsorption
mode. The polymeric beads were characterized before and after adsorption using
FTIR, XRD and EDX-SEM studies. The efficiency of the adsorbent was analyzed by
varying the parameters such as initial metal ion concentration, contact time,
adsorbent dose and pH. The experimental data obtained were fitted in the isotherm
models such as Langmuir, Freundlich and Tempkin models and in pseudo first and
second order kinetics studies. The isotherm and kinetics models revealed that the
adsorption was found to fit well with Freundlich isotherm and follows pseudo
second-order kinetics.
PMID- 26434526
TI - Synthesis and in vitro antifungal efficacy of oleoyl-chitosan nanoparticles
against plant pathogenic fungi.
AB - An antifungal dispersion system was prepared by oleoyl-chitosan (O-chitosan)
nanoparticles, and the antifungal activity against several plant pathogenic fungi
was investigated. Under scanning electron microscopy, the nanoparticles
formulation appeared to be uniform with almost spherical shape. The particle size
of nanoparticles was around 296.962 nm. Transmission electron microscopy
observation showed that nanoparticles could be well distributed in potato
dextrose agar medium. Mycelium growth experiment demonstrated that Nigrospora
sphaerica, Botryosphaeria dothidea, Nigrospora oryzae and Alternaria tenuissima
were chitosan-sensitive, while Gibberella zeae and Fusarium culmorum were
chitosan-resistant. The antifungal index was increased as the concentration of
nanoparticles increased for chitosan-sensitive fungi. Fatty acid analyses
revealed that plasma membranes of chitosan-sensitive fungi were shown to have
lower levels of unsaturated fatty acid than chitosan-resistant fungi.
Phylogenetic analysis based on ITS gene sequences indicated that two chitosan
resistant fungi had a near phylogenetic relationship. Results showed that O
chitosan nanoparticles could be a useful alternative for controlling pathogenic
fungi in agriculture.
PMID- 26434527
TI - A detailed study of homogeneous agarose/hydroxyapatite nanocomposites for load
bearing bone tissue.
AB - Agarose/hydroxyapatite (agar/HA) nanocomposites for load-bearing bone substitutes
were successfully fabricated via a novel in situ precipitation method.
Observation via SEM and TEM revealed that the spherical inorganic nanoparticles
of approximately 50 nm were well dispersed in the organic matrix, and the
crystallographic area combined closely with the amorphous area. The uniform
dispersion of HA nanoparticles had prominent effect on improving the mechanical
properties of the agar/HA nanocomposites (the highest elastic modulus: 1104.42
MPa; the highest compressive strength: 400.039 MPa), which proved to be potential
load-bearing bone substitutes. The thermal stability of agarose and
nanocomposites was also studied. The MG63 osteoblast-like cells on the composite
disks displayed fusiform and polygonal morphology in the presence of HA,
suggesting that the cell maturation was promoted. The results of cell
proliferation and cell differentiation indicated that the cells cultured on the
agar/HA composite disks significantly increased the alkaline phosphatase activity
and calcium deposition. The structural role of agarose in the composite system
was investigated to better understand the effect of biopolymer on structure and
properties of the composites. The optimal properties were the result of a
comprehensive synergy of the components.
PMID- 26434528
TI - The simultaneous production of sphingan Ss and poly(R-3-hydroxybutyrate) in
Sphingomonas sanxanigenens NX02.
AB - Sphingans and poly(R-3-hydroxybutyrate) (PHB) are both widely used biopolymers
produced by bacteria. In the batch fermentation of Sphingomonas sanxanigenens
NX02 in a 5L fermenter using glucose as carbon source, ivory colored sphingan Ss
production was a growth-associated process with a maximum purified production of
14.88 +/- 0.83 g/L, while 6.08 +/- 0.23 g/L PHB was simultaneously produced.
Sphingan Ss and PHB were separated by a simple dilution, heating and
centrifugation or filtration process, and sphingan Ss can be cost-effectively
extracted using a small amount of acid rather than multi-fold volumes of
alcohols. From ultrathin sections of S. sanxanigenens NX02, we found that the
interior space of the cells was filled with PHB granules, and the outside was
surrounded by abundant Ss. The purified sphingan Ss can be used as an excellent
gelling and emulsifying agent in biotechnology applications such as food,
personal care and production processes. Proposed pathways of Ss and PHB
biosynthesis from glucose are also presented.
PMID- 26434529
TI - Cardiovascular protective effect of polysaccharide from Ophiopogon japonicus in
diabetic rats.
AB - Ophiopogon japonicus (Thunb.) Ker-Gawl is a well known traditional Chinese
medicine used to treat cardiovascular and chronic inflammatory diseases for
thousands of years. The present study was set up to investigate the protective
effects of O. japonicus polysaccharide (OJP1) on cardiovascular injuries in
diabetic rats. Results showed that OJP1 significantly reduced the MDA
concentration and increased the activities of GPx, CAT and SOD in heart of
diabetic rats. The levels of AGE, hs-CRP, sICAM-1, NO and ET-1 in diabetic rats
were significantly reversed by OJP1 treatment. In addition, the level of ET-1
mRNA was decreased significantly, whereas eNOS mRNA level was increased after
administration of OJP1. Meanwhile, the histopathological analysis showed that
OJP1 alleviates the heart injury in diabetic rats. Together, these results
suggest that OJP1 maintains the antioxidant enzyme levels and improves
cardiovascular performance in diabetic rats.
PMID- 26434530
TI - Comparative safety evaluation of silica-based particles.
AB - PURPOSE: Silica nanoparticles (SNPs) are increasingly used as drug delivery
systems (DDS) and for biomedical imaging. Therapeutic and diagnostic agents can
be incorporated into the silica matrix to improve the stability and dissolution
of drug substances in biological systems. However, the safety of SNPs as drug
carriers remains controversial. To date, no validated and accepted nano-specific
tests exist to predict the potentially harmful impact of these materials on the
human body. METHODS: We synthesized by a systematic approach 12 different types
of SNPs with varying size, surface topology (porous vs non-porous), and surface
modifications. We characterized these particles in terms of dry state and
hydrodynamic diameter, specific surface area, and net surface charge (zeta
potential). For cellular studies, we exposed non-phagocytic (HepG2) cells,
phagocytic (THP-1) cells, and erythrocytes to SNPs. Cellular uptake and stability
of fluorescently labeled SNPs were analyzed by confocal microscopy and flow
cytometry. RESULTS: SNPs with a porous surface and negative net surface charge
had the strongest impact on cell viability. This is in contrast to non-porous
SNPs. None of the studied particles induced oxidative stress in either cell
lines. Particles with a negative surface charge induced hemolysis in a
concentration-dependent manner. CONCLUSIONS: Physico-chemical properties
promoting cytotoxicity and hemolysis were investigated. Our study revealed
potential hazards of spherical amorphous SNPs.
PMID- 26434531
TI - Transcriptional regulation of human paraoxonase 1 by PXR and GR in human hepatoma
cells.
AB - Human paraoxonase 1 (PON1) is A-esterase synthesized in the liver and secreted
into the plasma, where it associates with HDL. PON1 acts as an antioxidant
preventing lipid oxidation and detoxifies a wide range of substrates, including
organophosphate compounds. The variability of PON1 (enzyme activity/serum levels)
has been attributed to internal and external factors. However, the molecular
mechanisms involved in the transcriptional regulation of PON1 have not been well
studied. The aim of this study was to evaluate and characterize the
transcriptional activation of PON1 by nuclear receptors (NR) in human hepatoma
cells. In silico analysis was performed on the promoter region of PON1 to
determine the response elements of NR. Real-time PCR was used to evaluate the
effect of specific NR ligands on the mRNA levels of genes regulated by NR and
PON1. The results indicated that NR response elements had 95% homology to
pregnenolone (PXR), glucocorticoids (GR), retinoic acid (RXR) and peroxisomes
proliferator-activated receptor alpha (PPARalpha). Treatments with Dexamethasone
(GR ligand), Rifampicin (PXR ligand) and TCDD (AhR ligand) increased the mRNA
levels of PON1 at 24 and 48 h. We showed that the activation of GR by
Dexamethasone results in PON1 gene induction accompanied by an increase in
activity levels. In conclusion, these results demonstrate that GR regulates PON1
gene transcription through directly binding to NR response elements at -95 to
628 bp of the PON1 promoter. This study suggests new molecular mechanisms for the
transcriptional regulation of PON1 through a process involving the activation of
PXR.
PMID- 26434532
TI - Antigenotoxic, anti-photogenotoxic and antioxidant activities of natural
naphthoquinone shikonin and acetylshikonin and Arnebia euchroma callus extracts
evaluated by the umu-test and EPR method.
AB - The aim of this study was to evaluate the antigenotoxic and antioxidant potential
of shikonin (SH), acetylshikonin (ACS) and Arnebia euchroma callus extract (EXT).
The antigenotoxic activity was investigated by the umu-test as the inhibition of
the SOS system induction caused by genotoxic chemical agents - 4-nitroquinoline
oxide and 2-aminoanthracene. Moreover the ability of SH, ACS and EXT to prevent
photogenotoxicity triggered by chlorpromazine under UVA irradiation was measured.
The cytotoxicity of EXT toward V79 Chinese hamster cell line was additionally
assessed. Shikonin and acetylshikonin had no effect on 4-NQO induced genotoxicity
whereas EXT demonstrated an unclear effect. The protection against 2AA induced
genotoxicity was observed for all tested substances. The highest protection was
demonstrated for EXT with inhibition of 66%. SH and ACS reduced 2AA genotoxicity
with inhibition of about 60%. Under UVA the strongest and dose-dependent activity
was observed for EXT. Acetylshikonin was a weak anti-photogenotoxin whereas
shikonin had no clear effect. EXT was highly cytotoxic toward the V79 cell line -
the cells' morphology was affected seriously and apoptosis was impacted. The
antioxidant activity of SH, ACS and EXT was studied by means of electron
paramagnetic resonance spectroscopy using 2,2-diphenyl-1-picrylhydrazyl (DPPH)
radical. All three samples exhibited radical scavenging properties.
PMID- 26434533
TI - Speciation change and redistribution of arsenic in soil under anaerobic microbial
activities.
AB - Arsenic speciation and behavior in soil are strongly affected by redox
conditions. This work investigated speciation transformation and redistribution
of arsenic in soil under anaerobic conditions. The effect of microbial
sulfidogenesis on these processes was examined by addition of sulfate to the
incubation systems. As(III) was found to be the dominant arsenic species in
solution during the process of anaerobic incubation. The change of dissolved As
concentration with incubation time showed "M" shaped profiles, e.g. the curves
displaying two peaks at approximately 24 h and 240 h for the system with added
sulfate. Arsenic was released and reduced to As(III) in the early stage of the
incubation, and then resequestered into the solid phase. After excess sulfide was
generated, the resequestered arsenic was released again (probably due to the
dissolution of arsenic sulfide by dissolved sulfide ions) via the formation of
thioarsenite. At the end of the incubation process, most of the dissolved arsenic
was removed again from solution. The findings may have important implications to
the fate of arsenic in flooded sulfur-rich soils.
PMID- 26434534
TI - Evaluation of Ag nanoparticle coated air filter against aerosolized virus: Anti
viral efficiency with dust loading.
AB - In this study, the effect of dust loading on the anti-viral ability of an anti
viral air filter was investigated. Silver nanoparticles approximately 11 nm in
diameter were synthesized via a spark discharge generation system and were used
as anti-viral agents coated onto a medium air filter. The pressure drop,
filtration efficiency, and anti-viral ability of the filter against aerosolized
bacteriophage MS2 virus particles were tested with dust loading. The filtration
efficiency and pressure drop increased with dust loading, while the anti-viral
ability decreased. Theoretical analysis of anti-viral ability with dust loading
was carried out using a mathematical model based on that presented by Joe et al.
(J. Hazard. Mater.; 280: 356-363, 2014). Our model can be used to compare anti
viral abilities of various anti-viral agents, determine appropriate coating areal
density of anti-viral agent on a filter, and predict the life cycle of an anti
viral filter.
PMID- 26434535
TI - CdTe quantum dots as fluorescent probes to study transferrin receptors in
glioblastoma cells.
AB - BACKGROUND: Overexpression of transferrin receptors (TfRs), which are responsible
for the intracellular uptake of ferric transferrin (Tf), has been described in
various cancers. Although molecular biology methods allow the identification of
different types of receptors in cancer cells, they do not provide features about
TfRs internalization, quantification and distribution on cell surface. This
information can, however, be accessed by fluorescence techniques. In this work,
the quantum dots (QDs)' unique properties were explored to strengthen our
understanding of TfRs in cancer cells. METHODS: QDs were conjugated to Tf by
covalent coupling and QDs-(Tf) bioconjugates were applied to quantify and
evaluate the distribution of TfRs in two human glioblastoma cells lines, U87 and
DBTRG-05MG, and also in HeLa cells by using flow cytometry and confocal
microscopy. RESULTS: HeLa and DBTRG-05MG cells showed practically the same TfR
labeling profile by QDs-(Tf), while U87 cells were less labeled by bioconjugates.
Furthermore, inhibition studies demonstrated that QDs-(Tf) were able to label
cells with high specificity. CONCLUSIONS: HeLa and DBTRG-05MG cells presented a
similar and a higher amount of TfR than U87 cells. Moreover, DBTRG-05MG cells are
more efficient in recycling the TfR than the other two cells types. GENERAL
SIGNIFICANCE: This is the first study about TfRs in human glioblastoma cells
using QDs. This new fluorescent tool can contribute to our understanding of the
cancer cell biology and can help in the development of new therapies targeting
these receptors.
PMID- 26434536
TI - Functional expression and purification of Anabaena PCC 7120 XisA protein.
AB - Anabaena PCC 7120 xisA gene product mediates the site-specific excision of 11,278
bp nifD element in heterocysts formed under nitrogen starvation conditions.
Although XisA protein possesses both site-specific recombinase and endonuclease
activities, till date neither xisA transcript nor XisA protein has been detected.
Gene encoding XisA protein was isolated from plasmid pMX25 and overexpressed in
Escherichia coli BL21 DE3 yielding 7.7 mg enzyme per L of growth culture in
soluble fraction. His-tagged XisA was purified using Ni-NTA affinity
chromatography with 95% recovery. The purified XisA showed a single band on SDS
PAGE with molecular mass of 52 kDa. Identity of XisA was confirmed by MALDI-TOF
analysis and functionality of enzyme was confirmed using restriction digestion. A
PCR based method was developed to monitor excision by XisA, which displayed near
100% activity in E. coli within 1 h at 37 ( degrees )C on LB under static
condition.
PMID- 26434538
TI - Life-threatening hematuria in a hemodialysis patient with systemic light-chain
amyloidosis.
AB - BACKGROUND: Direct amyloid invasion of prostate tissue resulting in massive
bleeding may be fatal, and rapid diagnosis is difficult. CASE REPORT: A 71-y-old
male undergoing regular hemodialysis with primary light-chain (AL) amyloidosis
was admitted due to gross hematuria for 2 days. Cystoscopy revealed oozing from
the prostatic urethra. Therefore, electrocauterization was performed, and his
symptoms resolved. Unfortunately, he experienced recurrent massive hematuria 3
months later. Tests for serum D-dimer and fibrin degradation products were both
positive. Followed serum factor X level was low at 5.4%. Gross hematuria
persisted despite of blood transfusions, desmopressin, and vitamin K therapy.
Emergent cystoscopy revealed oozing from the prostatic urethra, as was found
previously. Therefore, electrocauterization and transurethral resection of the
prostate were performed. Analysis of a biopsy specimen of prostate demonstrated
strong amyloid deposition in the vascular and perivascular regions. Electron
microscopy showed relatively straight fibrils with diameters of 7-10nm in the
perivascular region. Gross hematuria subsided then, and no recurrence was noted
at a 6-month follow-up. CONCLUSIONS: Systemic AL amyloidosis can cause
potentially life-threatening hemorrhage. Hemostatic defects and direct invasion
with amyloid angiopathy are main pathogenic factors. Timely surgical intervention
may be imperative.
PMID- 26434539
TI - Palladium-catalyzed dearomative cyclization by a norbornene-mediated sequence: a
route to spiroindolenine derivatives.
AB - The first palladium-catalyzed dearomative cyclization via a modified Catellani
type C-H functionalization has been realized. The new strategy led to a series of
spiroindolenine derivatives bearing an all-carbon quaternary spirocenter from
simple aryl halides and substituted indoles.
PMID- 26434537
TI - Development of mesoporous silica-based nanoparticles with controlled release
capability for cancer therapy.
AB - Nanoparticles that respond to internal and external stimuli to carry out
controlled release of anticancer drugs have been developed. In this review, we
focus on the development of mesoporous silica based nanoparticles, as this type
of materials provides a relatively stable material that is amenable to various
chemical modifications. We first provide an overview of various designs employed
to construct MSN-based controlled release systems. These systems respond to
internal stimuli such as pH, redox state and the presence of biomolecules as well
as to external stimuli such as light and magnetic field. They are at a different
stage of development; depending on the system, their operation has been
demonstrated in aqueous solution, in cancer cells or in animal models. Efforts to
develop MSNs with multi-functionality will be discussed. Safety and
biodegradation of MSNs, issues that need to be overcome for clinical development
of MSNs, will be discussed. Advances in the synthesis of mechanized theranostic
nanoparticles open up the possibility to start envisioning future needs for
medical equipment.
PMID- 26434540
TI - CO2 capture and electrochemical conversion using superbasic [P66614][124Triz].
AB - The ionic liquid trihexyltetradecylphosphonium 1,2,4-triazolide,
[P66614][124Triz], has been shown to chemisorb CO2 through equimolar binding of
the carbon dioxide with the 1,2,4-triazolide anion. This leads to a possible new,
low energy pathway for the electrochemical reduction of carbon dioxide to formate
and syngas at low overpotentials, utilizing this reactive ionic liquid media.
Herein, an electrochemical investigation of water and carbon dioxide addition to
the [P66614][124Triz] on gold and platinum working electrodes is reported.
Electrolysis measurements have been performed using CO2 saturated
[P66614][124Triz] based solutions at -0.9 V and -1.9 V on gold and platinum
electrodes. The effects of the electrode material on the formation of formate and
syngas using these solutions are presented and discussed.
PMID- 26434541
TI - The effect of nanoclay on the rheology and dynamics of polychlorinated biphenyl.
AB - The thermal, rheological, and mechanical and dielectric relaxation properties of
exfoliated dispersions of montmorillonite clay in a molecular liquid,
polychlorobiphenyl (PCB), were studied. The viscosity enhancement at low
concentrations of clay (<=5%) exceeded by a factor of 50 the increase obtainable
with conventional fillers. However, the effect of the nanoclay on the local
dynamics, including the glass transition temperature, was quite small. All
materials herein conformed to density-scaling of the reorientation relaxation
time of the PCB for a common value of the scaling exponent. A new relaxation
process was observed in the mixtures, associated with PCB molecules in proximity
to the clay surface. This process has an anomalously high dielectric strength,
suggesting a means to exploit nanoparticles to achieve large electrical energy
absorption. This lower frequency dispersion has a weaker dependence on pressure
and density, consistent with dynamics constrained by interactions with the
particle surface.
PMID- 26434542
TI - Spontaneous growth of ultra-thin titanium oxides shell on Ag nanowires: an
electron energy loss spectroscope observation.
AB - Ag nanowires with a spontaneous ultra-thin TiO2 shell (~0.5 nm) can be grown on
TiO2 substrate. STEM/EELS results demonstrate that this oxygen-deficient TiO2
layer is formed through the oxidation of Ti which is released from the substrate
and segregated to the nanowire surface simultaneously with crystal growth of the
nanowires.
PMID- 26434543
TI - Mechanical properties of monolayer sulphides: a comparative study between MoS2,
HfS2 and TiS3.
AB - The in-plane stiffness (C), Poisson's ratio (nu), Young's modulus and ultimate
strength (sigma) along two different crystallographic orientations are calculated
for the single layer crystals: MoS2, HfS2 and TiS3 in 1H, 1T and monoclinic
phases. We find that MoS2 and HfS2 have isotropic in-plane stiffnesses of 124.24
N m(-1) and 79.86 N m(-1), respectively. While for TiS3 the in-plane stiffness is
highly anisotropic due to its monoclinic structure, with Cx = 83.33 N m(-1) and
Cy = 133.56 N m(-1) (x and y are parallel to its longer and shorter in-plane
lattice vectors.). HfS2 which is in the 1T phase has the smallest anisotropy in
its ultimate strength, whereas TiS3 in the monoclinic phase has the largest.
Along the armchair direction MoS2 has the largest sigma of 23.48 GPa, whereas
along y TiS3 has the largest sigma of 18.32 GPa. We have further analyzed the
band gap response of these materials under uniaxial tensile strain, and find that
they exhibit different behavior. Along both armchair and zigzag directions, the
band gap of MoS2 (HfS2) decreases (increases) as strain increases, and the
response is almost isotropic. For TiS3, the band gap decreases when strain is
along x, while if strain is along y, the band gap increases first and then
decreases beyond a threshold strain value. The different characteristics observed
in these sulphides with different structures shed light on the relationship
between the structure and properties, which is useful for applications in
nanotechnology.
PMID- 26434544
TI - A sensitive SERS detection of miRNA using a label-free multifunctional probe.
AB - A novel surface enhanced Raman scattering (SERS) detection method is fabricated
for miRNA based on a smart multifunctional probe for dual cyclical nucleic acid
strand-displacement polymerization (CNDP), achieving high sensitivity,
universality, rapid analysis, and good performance in real cell samples.
PMID- 26434545
TI - IR-Driven Photocatalytic Water Splitting with WO2-NaxWO3 Hybrid Conductor
Material.
AB - An IR-driven photocatalytic water splitting system based on WO2-NaxWO3 (x > 0.25)
hybrid conductor materials was established for the first time; this system can be
directly applied in seawater. The WO2-NaxWO3 (x > 0.25) hybrid conductor material
was readily prepared by a high-temperature reduction process of semiconductor
NaxWO3 (x < 0.25) nanowire bundles. A novel ladder-type carrier transfer process
is suggested for the established IR-driven photocatalytic water splitting system.
PMID- 26434546
TI - Quercetine attenuates the gentamicin-induced ototoxicity in a rat model.
AB - OBJECTIVES: The aim of this study is to evaluate the protective role of quercetin
in gentamicin-induced ototoxicity through an auditory brainstem response (ABR)
test and a histopathological evaluation of the cochlea. METHODS: In this study,
48 female adult Sprague-Dawley rats aged 20-22 weeks and weighing 200-250g were
used. An ABR test was carried out on all rats prior to drug administration, after
which, the rats were divided into four groups of 12 animals each. Drug
administration was gentamicin 120mg/kg plus ethanol in group one; gentamicin
120mg/kg plus quercetin 15mg/kg in group two; quercetin 15mg/kg in group three;
and ethanol in group four. The drugs were administered intraperitoneally once a
day for two weeks, and the ABR test was repeated after drug administration.
Subsequently, the rats were sacrificed and their cochleae were dissected and
examined histopathologically. RESULTS: There was no significant difference
between the pre-treatment ABR measurement values of the groups. However, a
significant increase was detected in the ABR values in the group of rats that
were administered gentamicin plus ethanol, while no statistically significant
increase was found in the ABR values in the groups administered with gentamicin
plus quercetin; quercetin alone; and ethanol alone. The number of TUNEL positive
cells in the inner and outer hair cells in the Corti organ was found to be fewer,
and Caspase 3 and 9 expressions were found to be weaker in the group receiving
gentamicin plus quercetin than in the group receiving gentamicin plus ethanol.
CONCLUSIONS: Auditory function was detected to be significantly protected and
apoptotic cells were found to be decreased when quercetin was administered
together with gentamicin. From these results it was concluded that quercetin, a
powerful antioxidant, attenuates ABR thresholds and histopathological lesions in
the cochlea in gentamicin-induced ototoxicity in rats.
PMID- 26434547
TI - Peripheral vestibular loss detected in pediatric patients using a smartphone
based test of the subjective visual vertical.
AB - INTRODUCTION: Detection of peripheral vestibular loss (PVL) in children with
dizziness is an important and challenging task. The static subjective visual
vertical (SVV) test can effectively detect PVL, but requires specialized
equipment. OBJECTIVE: The goal of this study was to determine the efficacy of a
smartphone-based SVV test at detecting PVL in pediatric patients. METHODS: Thirty
nine patients between 7 and 18 years old (mean=14.0+/-2.70) underwent
conventional SVV (conv-SVV) and smartphone-based SVV (ip-SVV) testing. Subjects
included 6 with PVL (based on clinical history and other vestibular tests), 6
with benign paroxysmal positioning vertigo (BPPV), 11 with central causes of
vertigo (CV), 8 with non-vestibular dizziness (NVD), and 8 controls. RESULTS:
Mean ip-SVV score in the PVL group (2.77+/-1.45) was significantly higher than in
each of the other groups (BPPV=0.89+/-0.55; CV=1.08+/-0.68; NVD=1.45+/-1.19;
Control=1.08+/-0.73; one-way analysis of variance, p=0.008), and remained
significant after adjusting for age and gender by multiple linear regression
analysis. Receiver operating characteristic analysis predicted an optimal ip-SVV
cut-off score of >2.13 degrees with a sensitivity of 66.7%, specificity of
97.0%, positive predictive value (PPV) of 80%, and negative predictive value of
94.1% for detecting PVL. Sensitivity and PPV improved to 75% and 100%,
respectively, when subjects tested >1 month after symptom onset (n=24) were
excluded. CONCLUSION: Smartphone-based SVV testing is a simple and useful office
based method for detecting PVL in children with dizziness.
PMID- 26434548
TI - Procalcitonin and community-acquired pneumonia (CAP) in children.
AB - The role of procalcitonin (PCT) as a biomarker for sepsis in adults is well
documented, while its role in infections affecting neonatal children remains
controversial. Among these infections, Community-Acquired pneumonia (CAP) has
been studied extensively, because it's the second cause of death in children in
developing countries, and one of the most frequent causes of hospitalization in
industrialized countries. The PubMed database and the Cochrane Library were used
to search for the following keywords: CAP, procalcitonin, and children. Thirteen
articles were studied to determine the role of PCT in CAP management,
specifically its usefulness for distinguishing pneumococcal infections from viral
and unknown infections, for predicting severity and the correct antibiotic
treatment. This paper focuses on the studies performed to identify the best
inflammatory biomarker for CAP management. Although there is an increase in
studies confirming the usefulness of PCT in CAP management in children, further
studies are needed to have better understanding of its role for pediatric CAP
management.
PMID- 26434549
TI - Negative interference of N-acetyl cysteine (NAC) on selected chemistries on the
Abbott architect platform.
PMID- 26434550
TI - WITHDRAWN: Dual display bacteriophage as a platform for high sensitive detection
of serum p53 antibodies in breast cancer patients.
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- 26434551
TI - Circadian time structure of circulating plasma lipid peroxides, antioxidant
enzymes and other small molecules in peptic ulcers.
AB - BACKGROUND: The circadian rhythm, as part of a broad time structure (chronome) of
lipid peroxides and antioxidant defense mechanisms may relate to prevention,
efficacy and management of preventive and curative chronotherapy. METHODS: Fifty
newly diagnosed patients with peptic ulcers, 30-45 years of age, and 60 age
matched clinically healthy volunteers were synchronized for one week with diurnal
activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was served
around 08:30, lunch around 13:30 and dinner around 20:30. Drugs known to affect
the free-radical systems were not taken. Blood samples were collected at 6-hour
intervals for 24h under standardized, presumably 24-hour synchronized conditions.
Plasma lipid peroxides, in the form of malondialdehyde (MDA), blood superoxide
dismutase (SOD), glutathione peroxide (GPx), glutathione reductase (GR), catalase
(CAT) activities, and serum total protein, albumin, ascorbic acid, total serum
cholesterol, and HDL-cholesterol concentrations were determined. RESULTS: By
population-mean cosinor analysis, a marked circadian variation was demonstrated
for all variables in healthy subjects and in ulcer patients (p<0.001). As
compared to controls, patients had a lower MESOR of MDA, SOD, GPx, GR, ascorbic
acid, and HDL-C. They also had smaller circadian amplitude of SOD, CAT, GPx, GR,
ascorbic acid, T-C, and HDL-C, but larger circadian amplitude of MDA and albumin.
As compared to healthy subjects, the circadian acrophase of ulcer patients
occurred later for MDA and GR and earlier for GPx. CONCLUSION: Mapping circadian
rhythms, important chronome components that include trends with age and extra
circadian components characterizing antioxidants and pro-oxidants, is needed for
exploring their putative role as markers in the treatment and management of
peptic ulcers.
PMID- 26434552
TI - Mass spectrometric phosphoproteome analysis of small-sized samples of human
neutrophils.
AB - BACKGROUND: Global analysis of stimulus-dependent changes in the neutrophil
phosphoproteome will improve the understanding of neutrophil signal transduction
and function in diverse disease settings. However, gel-free phosphoproteomics of
neutrophils in clinical studies is hampered by limited sample amounts and
requires protein extract stability, efficient tryptic digestion and sensitive
phosphopeptide enrichment in a protease-rich environment. For development of an
appropriate workflow, we assessed neutrophil protein stability in urea-based
lysis buffers and determined feasibility of gel-free phosphoproteomic analyses
using polymer-based metal ion affinity capture (PolyMAC). METHODS: Western
blotting, phosphopeptide enrichment and mass spectrometric analyses of samples of
neutrophils were performed. RESULTS: Degradation of proteins in neutrophil
extracts was observed after preparation with a urea-containing lysis buffer and
could be prevented by addition of highly concentrated protease inhibitors.
Subsequent tryptic digestion and PolyMAC-based phosphopeptide enrichment proved
efficient with accordingly prepared neutrophil samples. Applying the new
workflow, formyl-methionyl-leucyl-phenylalanine-induced phosphorylation of
extracellular signal-regulated kinases 1 and 2 (ERK1/2) was detected after gel
free and gel-based phosphoproteomic analyses as proof of principle from 20 ml of
whole blood. Furthermore, phosphorylation of other ERK1/2 pathway-associated
proteins was monitored. CONCLUSION: We provide a workflow for efficient, gel-free
phosphoproteome analyses with small-sized neutrophil samples, suitable for
application in clinical studies.
PMID- 26434554
TI - Bayesian approach for assessing non-inferiority in a three-arm trial with pre
specified margin.
AB - Non-inferiority trials are becoming increasingly popular for comparative
effectiveness research. However, inclusion of the placebo arm, whenever possible,
gives rise to a three-arm trial which has lesser burdensome assumptions than a
standard two-arm non-inferiority trial. Most of the past developments in a three
arm trial consider defining a pre-specified fraction of unknown effect size of
reference drug, that is, without directly specifying a fixed non-inferiority
margin. However, in some recent developments, a more direct approach is being
considered with pre-specified fixed margin albeit in the frequentist setup.
Bayesian paradigm provides a natural path to integrate historical and current
trials' information via sequential learning. In this paper, we propose a Bayesian
approach for simultaneous testing of non-inferiority and assay sensitivity in a
three-arm trial with normal responses. For the experimental arm, in absence of
historical information, non-informative priors are assumed under two situations,
namely when (i) variance is known and (ii) variance is unknown. A Bayesian
decision criteria is derived and compared with the frequentist method using
simulation studies. Finally, several published clinical trial examples are
reanalyzed to demonstrate the benefit of the proposed procedure.
PMID- 26434553
TI - Biofilm formation by Bacillus subtilis requires an endoribonuclease-containing
multisubunit complex that controls mRNA levels for the matrix gene repressor
SinR.
AB - Biofilm formation by Bacillus subtilis is largely governed by a circuit in which
the response regulator Spo0A turns on the gene for the anti-repressor SinI. SinI,
in turn, binds to and inactivates SinR, a dedicated repressor of genes for matrix
production. Mutants of the genes ylbF, ymcA and yaaT are blocked in biofilm
formation, but the mechanism by which they act has been mysterious. A recent
report attributed their role in biofilm formation to stimulating Spo0A activity.
However, we detect no measurable effect on the transcription of sinI. Instead, we
find that the block in biofilm formation is caused by an increase in the levels
of SinR and of its mRNA. Evidence is presented that YlbF, YmcA and YaaT interact
with, and control the activity of, RNase Y, which is known to destabilize sinR
mRNA. We also show that the processing of another target of RNase Y, cggR-gapA
mRNA, similarly depends on YlbF and YmcA. Our work suggests that sinR mRNA
stability is an additional posttranscriptional control mechanism governing the
switch to multicellularity and raises the possibility that YlbF, YmcA and YaaT
broadly regulate mRNA stability as part of an RNase Y-containing, multi-subunit
complex.
PMID- 26434555
TI - An Epitope-Specific Respiratory Syncytial Virus Vaccine Based on an Antibody
Scaffold.
AB - Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract
infections in children. We have generated an epitope-specific RSV vaccine by
grafting a neutralizing epitope (F-epitope) in its native conformation into an
immunoglobulin scaffold. The resulting antibody fusion exhibited strong binding
affinity to Motavizumab, an RSV neutralizing antibody, and effectively induced
potent neutralizing antibodies in mice. This work illustrates the potential of
the immunoglobulin molecule as a scaffold to present conformationally constrained
B-cell epitopes.
PMID- 26434556
TI - Reversible skin and hair depigmentation during chemotherapy with dasatinib for
chronic myeloid leukemia.
PMID- 26434557
TI - The Value of Genetic Risk Scores to Predict Hypertension.
PMID- 26434558
TI - Physical Activity Engagement in Young People with Down Syndrome: Investigating
Parental Beliefs.
AB - BACKGROUND: Despite the wide documentation of the physical/psychological benefits
derived from regular physical activity (PA), high levels of inactivity are
reported among people with Down syndrome. This study aims to explore parental
beliefs concerning involvement, facilitators/barriers and benefits of PA in young
people. METHOD: Semi-structured interviews were conducted with 13 parents of
young people with Down syndrome. RESULTS: Three facilitation themes were
identified: (i) the support derived from family; (ii) the availability of APA
(Adapted Physical Activity) expert instructors and coaches; (iii) the challenging
nature of sport activities. Three barrier themes were identified: (i) the lack of
APA expert coaches and specialized gyms; (ii) the characteristics of Down
syndrome; and (iii) the parental beliefs and worries. CONCLUSIONS: Family plays a
key role, as facilitator and barrier, to the participation of their children with
Down syndrome in PA. Crucial is the implementation of evidence-based exercise
programmes involving people with Down syndrome and their families.
PMID- 26434559
TI - Quality of life and late-effects among childhood brain tumor survivors: a mixed
method analysis.
AB - BACKGROUND: Reports on the quality of life (QOL) of childhood brain tumor (BT)
survivors have been inconsistent. As cognitive limitations may restrict their
participation in questionnaire-based studies, our aim was to evaluate in depth
the QOL with a mixed-method analysis. METHODS: The 5-year survivors of childhood
BTs born in 1975-2000 and alive in 2010 were identified via the Finnish Cancer
Registry and treating clinics. Twenty-one survivors (32%) participated in a mixed
method analysis including 15D (a general health-related QOL questionnaire), the
Beck Depression Inventory, and a qualitative semi-structured interview. RESULTS:
Based on the 15D-questionnaire, the BT survivors had an impaired health-related
QOL in several dimensions such as speech and usual activities. On the other hand,
no difference was found in other dimensions such as distress or vitality. A
majority (95%) of the survivors showed no increased risk for depression. The
qualitative interview revealed that the most important aspects affecting the QOL
of the survivors were positive mental growth, negative conceptions concerning
illness, living one day at a time, age at diagnosis, time since diagnosis, social
relationships, learning disabilities and limitations in vocational opportunities,
limitations in independent life, and changed understanding of the term 'health'.
CONCLUSIONS: Childhood BT survivors have heterogeneous attitudes on QOL. The
survivors assess social aspects to be more important than functionality for their
QOL. Social concerns should actively be brought up to offer support for those
with significant social difficulties. Interventions for social difficulties
should be more actively developed. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26434560
TI - Three-dimensional HDlive rendering of fetal perineum in anorectal atresia.
PMID- 26434561
TI - Sesame indicum, a nutritional supplement, elicits antiamnesic effect via
cholinergic pathway in scopolamine intoxicated mice.
AB - PURPOSE: Present study was undertaken to evaluate the antiamnesic effect of
Sesamum indicum (S. indicum) seeds (standardized for sesamin, a lignan, content)
in scopolamine, a muscarinic antagonist intoxicated mice. METHODS: Male Swiss
albino mice (18-22 g bw) were pretreated with methanolic extract of sesame seeds
(MSSE) (100 and 200 mg/kg/day, p.o) for a period of 14 days. Scopolamine (0.3
mg/kg, i.p.) was injected on day 14, 45 +/- 10 min after MSSE administration.
Antiamnesic effect of MSSE was evaluated using step-down latency (SDL) on passive
avoidance apparatus and transfer latency (TL) on an elevated plus maze. To
unravel the mechanism of action, we examined the effects of MSSE on the genes
such as acetyl cholinesterase (AChE), muscarinic receptor M1 subtype (mAChRM1 ),
and brain derived neurotrophic factor (BDNF) expression within hippocampus of
experimental mice. Further, its effects on bax and bcl-2 were also evaluated.
Histopathological examination of hippocampal CA1 region was performed using
cresyl violet staining. RESULTS: MSSE treatment produced a significant and dose
dependent increase in step down latency in passive avoidance test and decrease in
transfer latency in elevated plus maze in scopolamine intoxicated injected mice.
MSSE down-regulated AChE and mAChRM1 and up-regulated BDNF mRNA expression.
Further, it significantly down-regulated the bax and caspase 3 and up-regulated
bcl-2 expression in scopolamine intoxicated mice brains. Mice treated with MSSE
showed increased neuronal counts in hippocampal CA1 region when compared with
scopolamine-vehicle treated mice. CONCLUSION: Sesame seeds have the ability to
interact with cholinergic components involved in memory function/restoration and
also an interesting candidate to be considered for future cognitive research. (c)
2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1955-1963, 2016.
PMID- 26434562
TI - Calcium silicate-based cements: composition, properties, and clinical
applications.
AB - Mineral trioxide aggregate (MTA) is a calcium silicate-based cement (CSC)
commonly used in endodontic procedures involving pulpal regeneration and hard
tissue repair, such as pulp capping, pulpotomy, apexogenesis, apexification,
perforation repair, and root-end filling. Despite the superior laboratory and
clinical performance of MTA in comparison with previous endodontic repair
cements, such as Ca(OH)2 , MTA has poor handling properties and a long setting
time. New CSC have been commercially launched and marketed to overcome the
limitations of MTA. The aim of the present review was to explore the available
literature on new CSC products, and to give evidence-based recommendations for
the clinical use of these materials. Within the limitations of the available data
in the literature regarding the properties and performance of the new CSC, the
newer products could be promising alternatives to MTA; however, further research
is required to support this assumption.
PMID- 26434563
TI - A mixed-method synthesis of knowledge, experiences and attitudes of health
professionals to Female Genital Mutilation.
AB - AIM: To synthesize knowledge, attitudes and experiences of health professionals
about Female Genital Mutilation. BACKGROUND: Despite the World Health
Organization campaigning to stop FGM, and it being illegal in many countries, the
practice remains common in some countries and cultures. Migration has contributed
to the growth of this practice in countries where it was not previously carried
out. DESIGN: Mixed-method synthesis. DATA SOURCES: Search of ten electronic
databases: 2006-2014. Manual scanning of reference lists and summary feeds from
international organizations such as WHO, UN and UNICEF. REVIEW METHODS: Thematic
synthesis comparing country of origin where the practice was common with country
of residence where migrant women affected by the practice reside. 17 included
descriptive, quantitative, qualitative studies and grey literature studies in
English or Spanish. RESULTS: Seven themes were developed: Ignorance of FGM
practice and its consequences; Lack of adherence to FGM protocols and guidelines;
Socially constructed acceptance of FGM; Ignorance of legislation and legal status
of FGM; Condoning, sanctioning or supporting FGM; Lack of information and
training; Nurses and Midwives as key to protecting and supporting girls and women
CONCLUSIONS: Although some nurses and midwives are in the forefront of
eradicating FGM this is counterbalanced by health professionals (including nurses
and midwives) who condone, sanction or support the practice with some calling for
medicalization of FGM as a legitimate procedure. Girls at risk need better
protection and women affected need more competent and cultural care from health
professionals. Health and legal systems, professional regulation and governance,
and professional training require strengthening to eradicate FGM, prevent the
medicalization of FGM as an acceptable procedure, and to better manage the
lifelong consequences for affected girls and women.
PMID- 26434564
TI - Early renin-angiotensin system intervention is more beneficial than late
intervention in delaying end-stage renal disease in patients with type 2
diabetes.
AB - AIMS: To develop and validate a model to simulate progression of diabetic kidney
disease (DKD) from early onset until end-stage renal disease (ESRD), and to
assess the effect of renin-angiotensin system (RAS) intervention in early,
intermediate and advanced stages of DKD. METHODS: We used data from the BENEDICT,
IRMA-2, RENAAL and IDNT trials that assessed effects of RAS intervention in
patients with type 2 diabetes. We built a model with discrete disease stages
based on albuminuria and estimated glomerular filtration rate (eGFR). Using
survival analyses, we assessed the effect of RAS intervention on delaying ESRD in
early [eGFR>60 ml/min/1.73 m(2) and albumin:creatinine ratio (ACR) <30 mg/g],
intermediate (eGFR 30-60 ml/min/1.73 m(2) or ACR 30-300 mg/g) and advanced (eGFR
<30 ml/min/1.73 m(2) or ACR >300 mg/g) stages of DKD for patients in different
age groups. RESULTS: For patients at early, intermediate and advanced stage of
disease, whose mean age was 60 years and who received placebo, the median time to
ESRD was 21.4, 10.8 and 4.7 years, respectively. RAS intervention delayed the
predicted time to ESRD by 4.2, 3.6 and 1.4 years, respectively. The benefit of
early RAS intervention was more pronounced in younger patients; for example, for
patients with a mean age of 45 years, RAS intervention at early, intermediate or
advanced stage delayed ESRD by 5.9, 4.0 and 1.1 years versus placebo.
CONCLUSIONS: RAS intervention early in the course of proteinuric DKD is more
beneficial than late intervention in delaying ESRD.
PMID- 26434566
TI - Improving the sensitivity in chiral capillary electrophoresis.
AB - CE is known for being one of the most powerful analytical techniques when
performing enantioseparations due to its numerous advantages such as excellent
separation efficiency and extremely low solvents and reagents consumption, all of
them derived from the capillary small dimensions. Moreover, it is worth
highlighting that unlike in chromatographic techniques, in CE the chiral selector
is generally within the separation medium instead of being attached to the
separation column which makes the method optimization a more versatile task.
Despite its numerous advantages, when using UV-Vis detection, CE lacks of
sensitivity detection due to its short optical path length derived from the
narrow separation capillary. This issue can be overcome by means of different
approaches, either by sample treatment procedures or by in-capillary
preconcentration techniques or even by employing detection systems more sensitive
than UV-Vis, such as LIF or MS. The present review assembles the latest
contributions regarding improvements of sensitivity in chiral CE published from
June 2013 until May 2015, which follows the works included in a previous review
reported by Sanchez-Hernandez et al. [Electrophoresis 2014, 35, 12-27].
PMID- 26434565
TI - Diagnostic methods and treatment options for focal cortical dysplasia.
AB - Our inability to adequately treat many patients with refractory epilepsy caused
by focal cortical dysplasia (FCD), surgical inaccessibility and failures are
significant clinical drawbacks. The targeting of physiologic features of
epileptogenesis in FCD and colocalizing functionality has enhanced completeness
of surgical resection, the main determinant of outcome. Electroencephalography
(EEG)-functional magnetic resonance imaging (fMRI) and magnetoencephalography are
helpful in guiding electrode implantation and surgical treatment, and high
frequency oscillations help defining the extent of the epileptogenic dysplasia.
Ultra high-field MRI has a role in understanding the laminar organization of the
cortex, and fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly
sensitive for detecting FCD in MRI-negative cases. Multimodal imaging is
clinically valuable, either by improving the rate of postoperative seizure
freedom or by reducing postoperative deficits. However, there is no level 1
evidence that it improves outcomes. Proof for a specific effect of antiepileptic
drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in
mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights
into novel treatment options with mTOR inhibitors, which might represent an
example of personalized treatment of epilepsy based on the known mechanisms of
disease. The ketogenic diet (KD) has been demonstrated to be particularly
effective in children with epilepsy caused by structural abnormalities,
especially FCD. It attenuates epigenetic chromatin modifications, a master
regulator for gene expression and functional adaptation of the cell, thereby
modifying disease progression. This could imply lasting benefit of dietary
manipulation. Neurostimulation techniques have produced variable clinical
outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has
achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve
stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS)
requires further study. Although review of current strategies underscores the
serious shortcomings of treatment-resistant cases, initial evidence from novel
approaches suggests that future success is possible.
PMID- 26434567
TI - Effects of Aspergillus niger fermented rapeseed meal on nutrient digestibility,
growth performance and serum parameters in growing pigs.
AB - The aim of the present study was to investigate the influences of Aspergillus
niger fermented rapeseed meal (FRSM) on growth performance and nutrient
digestibility of growing pigs. A total of 72 growing pigs (body weight = 40.8 +/-
2.1 kg) were used in feeding trials, lasting for up to 42 days, and were randomly
allotted to one of three diets, including a corn-soybean meal control diet as
well as two experimental diets containing 10% unfermented rapeseed meal (RSM) or
10% FRSM. The results showed that average daily gain and feed conversion ratio of
pigs fed FRSM were superior (P < 0.05) to that of pigs fed unfermented RSM and
did not differ from the control. Pigs fed control diet had higher (P < 0.05)
total tract apparent digestibility for dry matter, protein, calcium and
phosphorus than pigs fed unfermented RSM diet and did not differ from the FRSM
diet. Pigs fed FRSM had lower levels (P < 0.05) of serum aspartate transaminase
compared to unfermented RSM. In conclusion, solid state fermentation using
Aspergillus niger may improve the growth performance and nutrient digestibility
of RSM for pigs and FRSM is a promising alternative protein for pig production.
PMID- 26434568
TI - Demystifying discharge: Assessing discharge readiness to predict day of
discharge.
PMID- 26434569
TI - Efficacy of Flow-Diverting Devices for Cerebral Aneurysms: A Systematic Review
and Meta-analysis.
AB - BACKGROUND: To evaluate the efficacy of flow-diverting devices (FDDs) used in the
treatment for intracranial aneurysms (IAs), we performed a meta-analysis of
published literature on FDDs. METHODS: A systematic electronic database search
was conducted using MEDLINE, PubMed, Springer, and EBSCO for all accessible
articles on FDDs published until December 2014. Abstracts, full-text manuscripts,
and the reference lists of retrieved articles were analyzed. Random effects meta
analysis was used to pool the occlusion rate outcomes across studies. RESULTS:
Fifty-nine studies containing efficacy data on 2263 patients with more than 2493
treated aneurysms were included in the analysis. The overall complete occlusion
rate was 82.5% (95% CI, 78.8%-86%) across studies. The success rate of FDD
implantation was 97.4% (95% CI, 95.4%-99.4%). The occlusion rate for anterior
circulation aneurysms was 83.3% (95% CI, 71.2%-95.4%); with regard to complete
occlusion, the odds ratio for anterior circulation aneurysms was significantly
higher than that of posterior circulation IAs (odds ratio, 1.93; 95% CI, 1.00
3.73). CONCLUSIONS: FDDs have high technical success rates in the management of
IAs. Additional studies on well-designed, multicenter, randomized controlled
trials will be required to validate the findings of the present study and to
identify the best therapeutic strategy for IAs depending on their size, location,
and characteristics.
PMID- 26434570
TI - Need of the Hour: Stimulating Medical and Nonmedical Students to Choose a Career
in Neuro and Spinal Surgery: A Perspective.
PMID- 26434571
TI - Importance of Continued Support for Microsurgical Anatomical Studies.
PMID- 26434572
TI - Poor-Grade Subarachnoid Hemorrhage Patients: Do We All Know the Best Way to
Manage?
PMID- 26434573
TI - A new signal characterization and signal-based Chou's PseAAC representation of
protein sequences.
AB - Most of the algorithms used for information extraction and for processing the
amino acid chains that make up proteins treat them as symbolic chains. Fewer
algorithms exploit signal processing techniques that require a numerical
representation of amino acid chains. However, these algorithms are very powerful
for extracting regularities that cannot be detected when working with a symbolic
chain, which may be important for understanding the biological meaning of a
sequence or in classification tasks. In this study, a new mathematical
representation of amino acid chains is proposed, which is derived using a
similarity measure based on the PAM250 amino acid substitution matrix and that
generates 20 signals for each protein sequence. Using this representation 20
consensus spectra for a protein family are determined and the relevance of the
frequency peaks is established, obtaining a group of significant frequency peaks
that manifest common periodicities of the amino acid sequences that belong to a
protein family. We also show that the proposed representation in 20 signals can
be integrated into Chou's pseudo amino acid composition (PseAAC) and constitute a
useful alternative to amino acid physicochemical properties in Chou's PseAAC.
PMID- 26434574
TI - Consistency of QSAR models: Correct split of training and test sets, ranking of
models and performance parameters.
AB - Recent implementations of QSAR modelling software provide the user with numerous
models and a wealth of information. In this work, we provide some guidance on how
one should interpret the results of QSAR modelling, compare and assess the
resulting models, and select the best and most consistent ones. Two QSAR datasets
are applied as case studies for the comparison of model performance parameters
and model selection methods. We demonstrate the capabilities of sum of ranking
differences (SRD) in model selection and ranking, and identify the best
performance indicators and models. While the exchange of the original training
and (external) test sets does not affect the ranking of performance parameters,
it provides improved models in certain cases (despite the lower number of
molecules in the training set). Performance parameters for external validation
are substantially separated from the other merits in SRD analyses, highlighting
their value in data fusion.
PMID- 26434575
TI - A snapshot of circulation failure following acute traumatic injury: The expansion
of computed tomography beyond injury diagnosis.
AB - OBJECTIVE: CT scans with a flat Inferior Vena Cava (IVC) suggest hypovolemia, and
the presence of shock bowel implies hypoperfusion. The purpose of this study is
to correlate injury severity, resuscitation needs, and clinical outcomes with CT
indices of hypovolemia and hypoperfusion. DESIGN: Retrospective cohort study.
SETTING: Level II trauma centre in Central California. PATIENTS: Adult patients
imaged with abdominal and pelvic CT scans, from January 2010-January 2011.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Circulatory derangements on
CT scans were defined as an IVC (AP) diameter measurement of <9 mm, flat IVC
(FIVC), hypovolemia. The presence of small intestine hypoperfusion was shock
bowel (SB). The absence of these findings was a normal CT scan (NCT). Comparisons
of acid-base status, fluids, morbidity and mortality were made based on CT
findings. Subgroups were: FIVC (n=20), FIVC+SB (n=19), SB (n=4) only versus
normal CT scans, NCT (n=47). RESULTS: Overall ISS was 19 (SD) 14. The lowest ISS
was in NCT 14 (SD) 10 and there was an incremental increase in ISS based on
circulatory derangements, p=0.001. ICU admission was lowest in NCT and highest in
the presence of hyovolemia and hypoperfusion, p=0.03. Similarly ED crystalloid
requirements and the activation of a massive transfusion protocol (MTP), was
lowest in NCT group and gradually increased significantly as hypovolemia and
hypoperfusion was demonstrated on CT scans. Additional parameters such as
metabolic acidosis, nosocomial infections and mortality were associated with
acute CT findings of circulatory failure. CONCLUSIONS: Hypovolemia and
hypoperfusion, markers of abnormal circulation, were demonstrated on CT scans for
trauma evaluation. The presence of these findings alone or in combination showed
strong correlation with high injury severity, and the need for aggressive
resuscitation.
PMID- 26434576
TI - Estimating pre-traumatic quality of life in patients with surgically treated
acetabular fractures and pelvic ring injuries: Does timing matter?
AB - BACKGROUND AND PURPOSE: Evaluation of patient-assessed functional outcome in
traumatic conditions has specific challenges. To obtain pre-traumatic data to
allow for comparison during follow-up, retrospective assessments are needed. How
such data is affected by posttraumatic time-point chosen for evaluation is
unknown. The primary purpose of this study was to investigate how the time-point
chosen for retrospective assessment of pre-traumatic quality of life (QoL) in
patients with surgically treated acetabular fractures and pelvic ring injuries
influenced the results. A secondary purpose was to examine the pre-traumatic QoL
profile in patients with these injuries. PATIENTS AND METHODS: 73 patients were
included, where 50 had an acetabular fracture and 23 a pelvic ring injury. Pre
traumatic QoL was evaluated using the generic instruments SF-36 and EQ5D in
conjunction with the condition-specific Pelvic Trauma Questionnaire (PTQ).
Questionnaires were completed at three time points: 0, 1 and 2 months post
surgery. RESULTS: Number of responders were 73 patients at 0 months, 61 patients
at 1 month and 53 patients at 2 months. 50 patients answered the questionnaires
at all three time-points. A trend was observed with all instruments where
patients estimated a better pre-traumatic status with narrower distributions when
assessment was delayed. At 2 months, scores for 4 out of 8 SF-36 domains where
significantly higher compared to 0 months. For EQ5D, EQ VAS improved at 1 and 2
months compared to month 0 results but no other significant differences between
time-points were found. Results from the PTQ demonstrated no significant
differences over time. Pre-traumatic quality of life was high and for SF-36
comparable to a population norm. A very low level of pre-existing discomfort from
the pelvic region was reported through the PTQ. CONCLUSION: Patients with
surgically treated acetabular fractures and pelvic ring injuries estimate a
higher pre-traumatic functional status when assessment is carried out at 1 or 2
months post-surgery compared to perioperative measurements. The SF-36 seems to be
more sensitive than the EQ5D in this respect. Pre-traumatic QoL in patients with
surgically treated acetabular fractures and pelvic ring injuries is generally
high and pre-existing discomfort from the pelvic region is uncommon.
PMID- 26434580
TI - Uncovering the sources of DNA found on the Turin Shroud.
AB - The Turin Shroud is traditionally considered to be the burial cloth in which the
body of Jesus Christ was wrapped after his death approximately 2000 years ago.
Here, we report the main findings from the analysis of genomic DNA extracted from
dust particles vacuumed from parts of the body image and the lateral edge used
for radiocarbon dating. Several plant taxa native to the Mediterranean area were
identified as well as species with a primary center of origin in Asia, the Middle
East or the Americas but introduced in a historical interval later than the
Medieval period. Regarding human mitogenome lineages, our analyses detected
sequences from multiple subjects of different ethnic origins, which clustered
into a number of Western Eurasian haplogroups, including some known to be typical
of Western Europe, the Near East, the Arabian Peninsula and the Indian sub
continent. Such diversity does not exclude a Medieval origin in Europe but it
would be also compatible with the historic path followed by the Turin Shroud
during its presumed journey from the Near East. Furthermore, the results raise
the possibility of an Indian manufacture of the linen cloth.
PMID- 26434582
TI - Enhancement of the Si p-n diode NIR photoresponse by embedding beta-FeSi2
nanocrystallites.
AB - By using solid phase epitaxy of thin Fe films and molecular beam epitaxy of Si, a
p(+)-Si/p-Si/beta-FeSi2 nanocrystallites/n-Si(111) diode structure was
fabricated. Transmission electron microscopy data confirmed a well-defined
multilayered structure with embedded nanocrystallites of two typical sizes: 3-4
and 15-20 nm, and almost coherent epitaxy of the nanocrystallites with the Si
matrix. The diode at zero bias conditions exhibited a current responsivity of 1.7
mA/W, an external quantum efficiency of about 0.2%, and a specific detectivity of
1.2 * 10(9) cm * Hz(1/2)/W at a wavelength of 1300 nm at room temperature. In the
avalanche mode, the responsivity reached up to 20 mA/W (2% in terms of
efficiency) with a value of avalanche gain equal to 5. The data obtained indicate
that embedding of beta-FeSi2 nanocrystallites into the depletion region of the Si
p-n junction results in expansion of the spectral sensitivity up to 1600 nm and
an increase of the photoresponse by more than two orders of magnitude in
comparison with a conventional Si p-n junction. Thereby, fabricated structure
combines advantage of the silicon photodiode functionality and simplicity with
near infrared light detection capability of beta-FeSi2.
PMID- 26434581
TI - mirPRo-a novel standalone program for differential expression and variation
analysis of miRNAs.
AB - Being involved in many important biological processes, miRNAs can regulate gene
expression by targeting mRNAs to facilitate their degradation or translational
inhibition. Many miRNA sequencing studies reveal that miRNA variations such as
isomiRs and "arm switching" are biologically relevant. However, existing
standalone tools usually do not provide comprehensive, detailed information on
miRNA variations. To deepen our understanding of miRNA variability, we developed
a new standalone tool called "mirPRo" to quantify known miRNAs and predict novel
miRNAs. Compared with the most widely used standalone program, miRDeep2, mirPRo
offers several new functions including read cataloging based on genome
annotation, optional seed region check, miRNA family expression quantification,
isomiR identification and categorization, and "arm switching" detection. Our
comparative data analyses using three datasets from mouse, human and chicken
demonstrate that mirPRo is more accurate than miRDeep2 by avoiding over-counting
of sequence reads and by implementing different approaches in adapter trimming,
mapping and quantification. mirPRo is an open-source standalone program
(https://sourceforge.net/projects/mirpro/).
PMID- 26434583
TI - Atypical role of sprouty in colorectal cancer: sprouty repression inhibits
epithelial-mesenchymal transition.
AB - Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we
demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer
(CRC) (Oncogene, 2010, 29: 5241-5253). We investigated the mechanisms by which
SPRY regulates epithelial-mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2
mRNA transcripts were significantly upregulated in human CRC. Suppression of
SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly
increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2
also increased E-cadherin and suppressed mesenchymal markers in colon cancer
cells. An inverse expression pattern between AKT2 and E-cadherin was established
in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that
interacts with AKT2 3' untranslated region. Mir-194 mimics increased E-cadherin
expression and suppressed cancer cell migration and invasion. By confocal
microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in
colon cancer cells transfected with miR-194. Spry1(-/-) and Spry2(-/-) double
mutant mouse embryonic fibroblasts exhibited decreased cell migration while
acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a
biomarker of poor prognosis.
PMID- 26434584
TI - Hepatitis C virus upregulates B-cell receptor signaling: a novel mechanism for
HCV-associated B-cell lymphoproliferative disorders.
AB - B-cell receptor (BCR) signaling is essential for the development of B cells and
has a critical role in B-cell neoplasia. Increasing evidence indicates an
association between chronic hepatitis C virus (HCV) infection and B-cell
lymphoma, however, the mechanisms by which HCV causes B-cell lymphoproliferative
disorder are still unclear. Herein, we demonstrate the expression of HCV viral
proteins in B cells of HCV-infected patients and show that HCV upregulates BCR
signaling in human primary B cells. HCV nonstructural protein NS3/4A interacts
with CHK2 and downregulates its activity, modulating HuR posttranscriptional
regulation of a network of target mRNAs associated with B-cell
lymphoproliferative disorders. Interestingly, the BCR signaling pathway was found
to have the largest number of transcripts with increased association with HuR and
was upregulated by NS3/4A. Our study reveals a previously unidentified role of
NS3/4A in regulation of host BCR signaling during HCV infection, contributing to
a better understanding of the molecular mechanisms underlying HCV-associated B
cell lymphoproliferative disorders.
PMID- 26434587
TI - Negative regulation of RNA-binding protein HuR by tumor-suppressor ECRG2.
AB - Esophageal cancer-related gene 2 (ECRG2) is a newer tumor suppressor whose
function in the regulation of cell growth and apoptosis remains to be elucidated.
Here we show that ECRG2 expression was upregulated in response to DNA damage, and
increased ECRG2 expression induced growth suppression in cancer cells but not in
non-cancerous epithelial cells. ECRG2-mediated growth suppression was associated
with activation of caspases and marked reduction in the levels of apoptosis
inhibitor, X chromosome-linked inhibitor of apoptosis protein (XIAP). ECRG2, via
RNA-binding protein human antigen R (HuR), regulated XIAP mRNA stability and
expression. Furthermore, ECRG2 increased HuR ubiquitination and degradation but
was unable to modulate the non-ubiquitinable mutant form of HuR. We also
identified missense and frame-shift ECRG2 mutations in various human malignancies
and noted that, unlike wild-type ECRG2, one cancer-derived ECRG2 mutant harboring
glutamic acid instead of valine at position 30 (V30E) failed to induce cell death
and activation of caspases. This naturally occurring V30E mutant also did not
suppress XIAP and HuR. Importantly, the V30E mutant overexpressing cancer cells
acquired resistance against multiple anticancer drugs, thus suggesting that ECRG2
mutations appear to have an important role in the acquisition of anticancer drug
resistance in a subset of human malignancies.
PMID- 26434586
TI - Nestin regulates proliferation and invasion of gastrointestinal stromal tumor
cells by altering mitochondrial dynamics.
AB - Nestin is widely expressed in numerous tumors and has become a diagnostic and
prognostic indicator. However, the exact mechanism by which nestin contributes to
tumor malignancy remains poorly understood. Here, we found marked upregulation of
nestin expression in highly proliferative and invasive gastrointestinal stromal
tumor (GIST) specimens. Nestin knockdown in GIST cells reduced the proliferative
and invasive activity owing to a decrease of mitochondrial intracellular reactive
oxygen species (ROS) generation. Furthermore, nestin was co-localized with
mitochondria, and knockdown of nestin increased mitochondrial elongation and
influenced the mitochondrial function, including oxygen consumption rates, ATP
generation and mitochondrial membrane potential and so on. In exploring the
underlying mechanism, we demonstrated nestin knockdown inhibited the
mitochondrial recruitment of Dynamin-related protein1 and induced the change of
mitochondrial dynamics. Thus, nestin may have an important role in GIST
malignancy by regulating mitochondrial dynamics and altering intracellular ROS
levels. The findings provide new clues to reveal mechanisms by which nestin
mediates the proliferation and invasion of GISTs.
PMID- 26434585
TI - The EGFR-HER2 module: a stem cell approach to understanding a prime target and
driver of solid tumors.
AB - The epidermal growth factor receptor (EGFR) and a coreceptor denoted HER2/ERBB2
are frequently overexpressed or mutated in solid tumors, such as carcinomas and
gliomas. In line with driver roles, cancer drugs intercepting EGFR or HER2
currently outnumber therapies targeting other hubs of signal transduction. To
explain the roles for EGFR and HER2 as prime drivers and targets, we take lessons
from invertebrates and refer to homeostatic regulation of several mammalian
tissues. The model we infer ascribes to the EGFR-HER2 module pivotal functions in
rapid clonal expansion of progenitors called transient amplifying cells (TACs).
Accordingly, TACs of tumors suffer from replication stress, and hence accumulate
mutations. In addition, several lines of evidence propose that in response to EGF
and related mitogens, TACs might undergo dedifferentiation into tissue stem
cells, which might enable entry of oncogenic mutations into the stem cell
compartment. According to this view, antibodies or kinase inhibitors targeting
EGFR-HER2 effectively retard some solid tumors because they arrest mutation
enriched TACs and possibly inhibit their dedifferentiation. Deeper understanding
of the EGFR-HER2 module and relations between cancer stem cells and TACs will
enhance our ability to control a broad spectrum of human malignancies.
PMID- 26434588
TI - Exosomes mediate the acquisition of the disease phenotypes by cells with normal
genome in tuberous sclerosis complex.
AB - Functions of extracellular vesicles including exosomes in the pathogenesis of
tuberous sclerosis complex (TSC) have not yet been studied. We report that the
extracellular vesicles such as exosomes derived from tuberous sclerosis 1 (Tsc1)
null cells transform phenotypes of neighboring wild-type cells in vivo in such
manner that they become functionally similar to Tsc1-null cells. The loss of Tsc1
in the mouse neural tube increases the number of the wild-type neuronal
progenitors, which is followed by the precocious and transient acceleration of
neuronal differentiation of these cells. The mechanisms regulating these changes
involve the exosomal delivery of exosomal shuttle Notch1 and Rheb esRNA and
component of gamma-secretase complex presenilin 1 from Tsc1-null cells to wild
type cells leading to the activation of Notch and Rheb signaling in the recipient
cells. The exosome-mediated mechanisms may also operate in the cells of
angiomyolipoma (AML), which develops as a result of mutations in TSC1/TSC2 genes
in TSC patients, because we observed the reactivation of mammalian target of
rapamycin and Notch pathways, driven by the delivery of Rheb and Notch1 esRNA, in
AML cells depleted of Rheb that were treated with the exosomes purified from AML
cells with the constitutively high Rheb levels.
PMID- 26434589
TI - DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor
MEIS1 in acute myeloid leukemia.
AB - Close to half of de novo acute myeloid leukemia (AML) cases do not exhibit any
cytogenetic aberrations. In this regard, distortion of the DNA methylation
setting and the presence of mutations in epigenetic modifier genes can also be
molecular drivers of the disease. In recent years, somatic missense mutations of
the DNA methyltransferase 3A (DNMT3A) have been reported in ~20% of AML patients;
however, no obvious critical downstream gene has been identified that could
explain the role of DNMT3A in the natural history of AML. Herein, using whole
genome bisulfite sequencing and DNA methylation microarrays, we have identified a
key gene undergoing promoter hypomethylation-associated transcriptional
reactivation in DNMT3 mutant patients, the leukemogenic HOX cofactor MEIS1. Our
results indicate that, in the absence of mixed lineage leukemia fusions, an
alternative pathway for engaging an oncogenic MEIS1-dependent transcriptional
program can be mediated by DNMT3A mutations.
PMID- 26434590
TI - AP2alpha controls the dynamic balance between miR-126&126* and miR-221&222 during
melanoma progression.
AB - Accumulating evidences have shown the association between aberrantly expressed
microRNAs (miRs) and cancer, where these small regulatory RNAs appear to dictate
the cell fate by regulating all the main biological processes. We demonstrated
the responsibility of the circuitry connecting the oncomiR-221&222 with the tumor
suppressors miR-126&126* in melanoma development and progression. According to
the inverse correlation between endogenous miR-221&222 and miR-126&126*,
respectively increasing or decreasing with malignancy, their enforced expression
or silencing was sufficient for a reciprocal regulation. In line with the
opposite roles of these miRs, protein analyses confirmed the reverse expression
pattern of miR-126&126*-targeted genes that were induced by miR-221&222. Looking
for a central player in this complex network, we revealed the dual regulation of
AP2alpha, on one side directly targeted by miR-221&222 and on the other a
transcriptional activator of miR-126&126*. We showed the chance of restoring miR
126&126* expression in metastatic melanoma to reduce the amount of mature
intracellular heparin-binding EGF like growth factor, thus preventing
promyelocytic leukemia zinc finger delocalization and maintaining its repression
on miR-221&222 promoter. Thus, the low-residual quantity of these two miRs
assures the release of AP2alpha expression, which in turn binds to and induces
miR-126&126* transcription. All together these results point to an unbalanced
ratio functional to melanoma malignancy between these two couples of miRs. During
progression this balance gradually moves from miR-126&126* toward miR-221&222.
This circuitry, besides confirming the central role of AP2alpha in orchestrating
melanoma development and/or progression, further displays the significance of
these miRs in cancer and the option of utilizing them for novel therapeutics.
PMID- 26434591
TI - Metabolic targeting of oncogene MYC by selective activation of the proton-coupled
monocarboxylate family of transporters.
AB - Deregulation of the MYC oncogene produces Myc protein that regulates multiple
aspects of cancer cell metabolism, contributing to the acquisition of building
blocks essential for cancer cell growth and proliferation. Therefore, disabling
Myc function represents an attractive therapeutic option for cancer treatment.
However, pharmacological strategies capable of directly targeting Myc remain
elusive. Here, we identified that 3-bromopyruvate (3-BrPA), a drug candidate that
primarily inhibits glycolysis, preferentially induced massive cell death in human
cancer cells overexpressing the MYC oncogene, in vitro and in vivo, without
appreciable effects on those exhibiting low MYC levels. Importantly,
pharmacological inhibition of glutamine metabolism synergistically potentiated
the synthetic lethal targeting of MYC by 3-BrPA due in part to the metabolic
disturbance caused by this combination. Mechanistically, we identified that the
proton-coupled monocarboxylate transporter 1 (MCT1) and MCT2, which enable
efficient 3-BrPA uptake by cancer cells, were selectively activated by Myc. Two
regulatory mechanisms were involved: first, Myc directly activated MCT1 and MCT2
transcription by binding to specific recognition sites of both genes; second, Myc
transcriptionally repressed miR29a and miR29c, resulting in enhanced expression
of their target protein MCT1. Of note, expressions of MCT1 and MCT2 were each
significantly elevated in MYCN-amplified neuroblastomas and C-MYC-overexpressing
lymphomas than in tumors without MYC overexpression, correlating with poor
prognosis and unfavorable patient survival. These results identify a novel
mechanism by which Myc sensitizes cells to metabolic inhibitors and validate 3
BrPA as potential Myc-selective cancer therapeutics.
PMID- 26434592
TI - Oxidative pentose phosphate pathway inhibition is a key determinant of
antimalarial induced cancer cell death.
AB - Despite immense interest in using antimalarials as autophagy inhibitors to treat
cancer, it remains unclear whether these agents act predominantly via autophagy
inhibition or whether other pathways direct their anti-cancer properties. By
comparing the treatment effects of the antimalarials chloroquine (CQ) and
quinacrine (Q) on KRAS mutant lung cancer cells, we demonstrate that inhibition
of the oxidative arm of the pentose phosphate pathway (oxPPP) is required for
antimalarial induced apoptosis. Despite inhibiting autophagy, neither CQ
treatment nor RNAi against autophagy regulators (ATGs) promote cell death. In
contrast, Q triggers high levels of apoptosis, both in vitro and in vivo, and
this phenotype requires both autophagy inhibition and p53-dependent inhibition of
the oxPPP. Simultaneous genetic targeting of the oxPPP and autophagy is
sufficient to trigger apoptosis in lung cancer cells, including cells lacking
p53. Thus, in addition to reduced autophagy, oxPPP inhibition serves as an
important determinant of antimalarial cytotoxicity in cancer cells.
PMID- 26434593
TI - More complex transcriptional regulation and stress response by MOF.
AB - MOF (males absent on the first) was initially discovered as a dosage compensation
factor that regulates the epigenetic acetylation of histone H4 lysine 16. In this
issue, Sheikh et al. demonstrate that MOF expression is not required for normal
kidney tissue function but is required for maintaining transcriptional regulation
under conditions of stress. This work along with results from previous
investigators highlights the importance of the cell lineage-chromatin
modification interaction in determining transcriptional programs and
physiological outcomes under normal and stress conditions.
PMID- 26434595
TI - TAMing resistance to multi-targeted kinase inhibitors through Axl and Met
inhibition.
AB - TAM (Tyro3-Axl-Mer) receptor tyrosine kinases and Met are implicated in several
hallmarks of cancer progression including sustained angiogenesis, enhanced
motility, tissue invasion and acquisition of metastatic potential through the
upregulation of epithelial-to-mesenchymal transition. Increasing evidence has
confirmed Axl and Met as emerging central drivers of adaptive resistance to
targeted therapies across a wide variety of cancers. In this issue of Oncogene,
Zhou et al. describe the mechanisms linking Axl and Met activation to acquired
resistance to sunitinib in renal cell carcinoma (RCC), providing a pre-clinical
rationale for the development of Axl and Met inhibitors including cabozantinib in
anti-angiogenic resistant RCC.
PMID- 26434594
TI - PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the
Golgi and affect clinical outcome in colorectal cancer.
AB - Tumour cells can use strategies that make them resistant to nutrient deprivation
to outcompete their neighbours. A key integrator of the cell's responses to
starvation and other stresses is amino-acid-dependent mechanistic target of
rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and
lysosomes is facilitated by amino-acid transporters within the solute-linked
carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36
family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter
4 (PAT4), in colorectal cancer. We show that independent of other major
pathological factors, high PAT4 expression is associated with reduced relapse
free survival after colorectal cancer surgery. Consistent with this, PAT4
promotes HCT116 human colorectal cancer cell proliferation in culture and tumour
growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4
regulates a form of mTORC1 with two distinct properties: first, it preferentially
targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1),
and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells
two non-essential amino acids, glutamine and serine, which are often rapidly
metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4
dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance
in human embryonic kidney-293 cells. PAT4 is predominantly associated with the
Golgi apparatus in a range of cell types, and in situ proximity ligation analysis
shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi.
These findings, together with other studies, suggest that differentially
localised intracellular amino-acid transporters contribute to the activation of
alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer
cells with high PAT4 expression will be more resistant to depletion of serine and
glutamine, allowing them to survive and outgrow neighbouring normal and
tumorigenic cells, and potentially providing a new route for pharmacological
intervention.
PMID- 26434596
TI - Histopathological features of sinonasal inverted papillomas in chinese patients.
AB - OBJECTIVES/HYPOTHESIS: Nasal inverted papilloma (IP) is a benign tumor with high
recurrence rates. Evidence of inflammation has been reported in IP in Caucasian
studies. This study aimed to investigate the histopathological patterns and their
associations with clinical characteristics in Chinese patients with IP. STUDY
DESIGN: Basic science study. METHODS: IP tissues were obtained from 50 Chinese
patients with unilateral IPs. Biopsies of inferior turbinate mucosa from 17
healthy subjects were used as controls. The histological patterns and severity of
epithelial remodeling and inflammatory cell infiltration were evaluated and
analyzed for associations with clinical characteristics. RESULTS: Thirty-one
percent of IP specimens were classified as grade I (mild remodeling) and 49% as
grade II (moderate and severe remodeling). Concomitant inflammatory nasal polyps
were found in 14 patients (28%). Recurrent IP was strongly associated with grade
II (odds ratio: 5.81, 95% confidence interval: 1.34-25.18). Except CD4(+) T
cells, quantities of neutrophils, macrophages, eosinophils, CD8(+) T cells, and
FoxP3(+) T-reg cells were significantly elevated in IP. Of these, neutrophils
were the predominant cell type in IP. CONCLUSIONS: Inflammation may have
potential roles in IPs and the higher grade of epithelial remodeling was
associated with the recurrence of IPs. LEVEL OF EVIDENCE: NA.
PMID- 26434597
TI - Determination of the hyperfine magnetic field in magnetic carbon-based materials:
DFT calculations and NMR experiments.
AB - The prospect of carbon-based magnetic materials is of immense fundamental and
practical importance, and information on atomic-scale features is required for a
better understanding of the mechanisms leading to carbon magnetism. Here we
report the first direct detection of the microscopic magnetic field produced at
(13)C nuclei in a ferromagnetic carbon material by zero-field nuclear magnetic
resonance (NMR). Electronic structure calculations carried out in nanosized model
systems with different classes of structural defects show a similar range of
magnetic field values (18-21 T) for all investigated systems, in agreement with
the NMR experiments. Our results are strong evidence of the intrinsic nature of
defect-induced magnetism in magnetic carbons and establish the magnitude of the
hyperfine magnetic field created in the neighbourhood of the defects that lead to
magnetic order in these materials.
PMID- 26434598
TI - Time-of-Flight Microwave Camera.
AB - Microwaves can penetrate many obstructions that are opaque at visible
wavelengths, however microwave imaging is challenging due to resolution limits
associated with relatively small apertures and unrecoverable "stealth" regions
due to the specularity of most objects at microwave frequencies. We demonstrate a
multispectral time-of-flight microwave imaging system which overcomes these
challenges with a large passive aperture to improve lateral resolution, multiple
illumination points with a data fusion method to reduce stealth regions, and a
frequency modulated continuous wave (FMCW) receiver to achieve depth resolution.
The camera captures images with a resolution of 1.5 degrees, multispectral images
across the X frequency band (8 GHz-12 GHz), and a time resolution of 200 ps (6 cm
optical path in free space). Images are taken of objects in free space as well as
behind drywall and plywood. This architecture allows "camera-like" behavior from
a microwave imaging system and is practical for imaging everyday objects in the
microwave spectrum.
PMID- 26434599
TI - Repertory of eukaryotes (eukaryome) in the human gastrointestinal tract: taxonomy
and detection methods.
AB - Eukaryotes are an important component of the human gut, and their relationship
with the human host varies from parasitic to commensal. Understanding the
diversity of human intestinal eukaryotes has important significance for human
health. In the past few decades, most of the multitudes of techniques that are
involved in the diagnosis of the eukaryotic population in the human intestinal
tract were confined to pathological and parasitological aspects that mainly rely
on traditionally based methods. However, development of culture-independent
molecular techniques comprised of direct DNA extraction from faeces followed by
sequencing, offer new opportunities to estimate the occurrence of eukaryotes in
the human gut by providing data on the entire eukaryotic community, particularly
not-yet-cultured or fastidious organisms. Further broad surveys of the eukaryotic
communities in the gut based on high throughput tools such as next generation
sequencing might lead to uncovering the real diversity of these ubiquitous
organisms in the human intestinal tract and discovering the unrecognized roles of
these eukaryotes in modulating the host immune system and inducing changes in
host gut physiology and ecosystem.
PMID- 26434600
TI - Awake Flexible Fiberoptic Laryngoscopy to diagnose glossoptosis in Robin Sequence
patients.
AB - BACKGROUND: Robin Sequence (RS) is usually defined as the combination of
micrognathia, glossoptosis and upper airway obstruction. No objective criteria to
diagnose RS exist. To compare management strategy results, a single RS definition
using objective criteria is needed. The most frequently used primary diagnostic
tool for glossoptosis is awake Flexible Fiberoptic Laryngoscopy (aFFL).
OBJECTIVES: To determine the reliability of the aFFL videos as an independent
diagnostic tool itself, rather than on the complete evaluation of a patient.
DESIGN, SETTING, PARTICIPANTS: All RS individuals from an existing cohort with an
available aFFL video were included retrospectively. Thirty age-matched patients
without pathologic findings on aFFL were used as controls. aFFL videos were
scored by six otolaryngologists as: a. Marked glossoptosis, b. Mild glossoptosis,
c. Severity unknown, d. No glossoptosis, e. Insufficient video quality. Videos
were anonymised and rated twice, in altered sequences, after a washout period of
minimally 2 weeks. MAIN OUTCOME MEASURES: Inter-rater and intrarater agreement.
RESULTS: Twenty-six videos of 16 RS patients and 30 videos of controls were
included. Inter-rater agreement was fair in the whole group (kappa: 0.320) and RS
group (kappa: 0.226), and fair to moderate in determining presence of
glossoptosis (total group kappa: 0.430; RS kappa: 0.302; controls kappa: 0.212).
The intrarater agreement for the presence of glossoptosis in RS was moderate
(kappa: 0.541). CONCLUSIONS: aFFL offers fair to moderate inter-rater agreement,
with moderate intrarater agreement, in evaluating glossoptosis in RS. Using aFFL
as the single tool in choosing management strategies in RS seems insufficient.
There is need for a more reliable, patient friendly diagnostic tool or an
internationally accepted aFFL scoring system, to diagnose glossoptosis in RS.
PMID- 26434601
TI - Expression of Heat Shock Protein 27 in Benign Prostatic Hyperplasia with Chronic
Inflammation.
AB - BACKGROUND: Heat shock protein 27 (HSP 27) is known as a mediator in immune
response and has been recently found to be expressed in prostate cancer. This
study aimed to investigate the role of HSP27 in inflammatory BPH. MATERIAL AND
METHODS: Hospitalized BPH patients who received TURP were divided into 4 groups
by the presence and degrees of chronic inflammation: non-inflammatory BPH (NI
BPH), mild-inflammatory BPH (MI BPH), moderate-inflammatory BPH (MOI BPH), and
severe-inflammatory BPH (SI BPH). Expressions of HSP 27, TNF-alpha, IL-6, and CD3
in prostate tissues and serum of patients were detected by immunohistochemistry
and ELISA. RESULTS: Expression of HSP27 in BPH with histological inflammation was
significantly higher than in non-inflammatory BPH. In inflammatory BPH groups,
HSP27 expression gradually increased along with increasing inflammation. There
was a significant correlation between the expression of TNF-alpha, IL-6, CD3 and
HSP27 among different inflammatory BPH groups. CONCLUSIONS: HSP27 expression
level is associated with the degree of chronic inflammation in BPH and may
participate in the pathological process in inflammatory BPH.
PMID- 26434602
TI - Modulation of embryonic development due to mating with immunised males.
AB - The modification of pre- and postnatal development conferred by immunogenic
stimulation of mothers provides a population-level adaptation mechanism for non
genetic transfer of maternal experiences to progeny. However little is known
about the transmission of paternal immune experiences to offspring. Here, we show
that immune priming of males 3-9 days before mating affects the growth and
humoral environment of developing embryos of outbred (ICR) and inbred (C57BL and
BALB/c) mice. Antigenic stimulation of fathers caused a significant increase in
embryonic bodyweight as measured on Day 16 of pregnancy and altered other
gestation parameters, such as feto-placental ratio. Pregnant females mated with
immunised males were also characterised by changes in humoral conditions as shown
by measurements of blood and amniotic progesterone, testosterone and granulocyte
macrophage colony-stimulating factor (GM-CSF) cytokine concentrations. These
results emphasise the role of paternal effects of immune priming on the in utero
environment and fetal growth.
PMID- 26434603
TI - A Hafnium-Based Metal-Organic Framework as a Nature-Inspired Tandem Reaction
Catalyst.
AB - Tandem catalytic systems, often inspired by biological systems, offer many
advantages in the formation of highly functionalized small molecules. Herein, a
new metal-organic framework (MOF) with porphyrinic struts and Hf6 nodes is
reported. This MOF demonstrates catalytic efficacy in the tandem oxidation and
functionalization of styrene utilizing molecular oxygen as a terminal oxidant.
The product, a protected 1,2-aminoalcohol, is formed selectively and with high
efficiency using this recyclable heterogeneous catalyst. Significantly, the
unusual regioselective transformation occurs only when an Fe-decorated Hf6 node
and the Fe-porphyrin strut work in concert. This report is an example of
concurrent orthogonal tandem catalysis.
PMID- 26434604
TI - Patterned Poly(acrylic acid) Brushes Containing Gold Nanoparticles for Peptide
Detection by Surface-Assisted Laser Desorption/Ionization Mass Spectrometry.
AB - Patterned poly(acrylic acid) (PAA) brushes was successfully generated via
photolithography and surface-initiated reversible addition-fragmentation chain
transfer (RAFT) polymerization of acrylic acid as verified by water contact angle
measurements and FT-IR analysis. The carboxyl groups of PAA brushes can act as
reducing moieties for in situ synthesis of gold nanoparticles (AuNPs), without
the use of additional reducing agent. The formation of AuNPs was confirmed by
transmission electron microscopy and X-ray photoelectron spectroscopy. The glass
surface-modified by PAA brushes and immobilized with AuNPs (AuNPs-PAA) can be
used as a substrate for SALDI-MS analysis, which is capable of detecting both
small peptides having m/z <= 600 (glutathione) and large peptides having m/z >=
1000 (bradykinin, ICNKQDCPILE) without the interference from matrix signal
suggesting that AuNPs were stably trapped within the PAA brushes and the carboxyl
groups of PAA can serve as internal proton source. By employing AuNPs as the
capture probe, the AuNPs-PAA substrate can selectively identify thiol-containing
peptides from the peptide mixtures with LOD as low as 0.1 and 0.05 nM for
glutathione and ICNKQDCPILE, respectively. An ability to selectively detect
ICNKQDCPILE in a diluted human serum is also demonstrated. The patterned format
together with its high sensitivity and selectivity render this newly developed
substrate a potential platform for high-throughput analysis of other biomarkers,
especially those with low molecular weight in complex biological samples.
PMID- 26434605
TI - Bioinspired Hierarchical Surface Structures with Tunable Wettability for
Regulating Bacteria Adhesion.
AB - To circumvent the influence from varied topographies, the systematic study of
wettability regulated Gram-positive bacteria adhesion is carried out on
bioinspired hierarchical structures duplicated from rose petal structures. With
the process of tuning the interfacial chemical composition of the self-assembled
films from supramolecular gelators, the varied wettable surfaces from
superhydrophilicity to superhydrophobicity can be obtained. The investigation of
Gram-positive bacteria adhesion on the hierarchical surfaces reveals that Gram
positive bacteria adhesion is crucially mediated by peptidoglycan due to its
different interaction mechanisms with wettable surfaces. The study makes it
possible to systematically study the influence mechanism of wettability regulated
bacteria adhesion and provides a sight to make the bioinspired topographies in
order to investigate wettability regulated bioadhesion.
PMID- 26434606
TI - Quantum Chemical Study of the Thermochemical Properties of Organophosphorous
Compounds.
AB - Organophosphorous compounds are involved in many toxic compounds such as
fungicides, pesticides, or chemical warfare nerve agents. The understanding of
the decomposition chemistry of these compounds in the environment is largely
limited by the scarcity of thermochemical data. Because of the high toxicity of
many of these molecules, experimental determination of their thermochemical
properties is very difficult. In this work, standard gas-phase thermodynamic
data, i.e., enthalpies of formation (DeltafH298 degrees ), standard entropies
(S298 degrees ), and heat capacities (Cp degrees (T)), were determined using
quantum chemical calculations and more specifically the CBS-QB3 composite method,
which was found to be the best compromise between precision and calculation time
among high accuracy composite methods. A large number of molecules was
theoretically investigated, involving trivalent and pentavalent phosphorus atoms,
and C, H, O, N, S, and F atoms. These data were used to propose 83 original
groups, used in the semiempirical group contribution method proposed by Benson.
Thanks to these latter group values, thermochemical properties of several nerve
agents, common pesticides and herbicides have been evaluated. Bond dissociations
energies (BDE), useful for the analysis the thermal stability of the compounds,
were also determined in several molecules of interest.
PMID- 26434607
TI - Efficient, Solvent-Free, Multicomponent Method for Organic-Base-Catalyzed
Synthesis of beta-Phosphonomalonates.
AB - An efficient, one-pot, di-n-butylamine-catalyzed, three-component synthesis of
beta-phosphonomalonates has been developed. A wide range of substrates, including
aromatic and fused aromatic aldehydes, were condensed with enolizable C-H
activated compounds and dialkylphosphites to give the desired products in
excellent yields. This method provides an eco-friendly alternative approach to
rapid construction of a diversity-oriented library of beta-phosphonomalonates.
PMID- 26434608
TI - One-Pot Synthesis of Monodisperse Noble Metal @ Resorcinol-Formaldehyde (M@RF)
and M@Carbon Core-Shell Nanostructure and Their Catalytic Applications.
AB - We demonstrate that noble metal @ RF core-shell nanostructures can be obtained
through a facile one-pot synthesis approach in the absence of any additional
surfactants. Monodisperse metal@RF core-shell nanostructures can be produced
within 1 h on a large scale. Both the core size and shell thickness can be
readily tuned by altering the reaction parameters. Systematic studies reveal that
resorcinol could have several functions: it could act as a reactant to form RF
resin, and it also could passivate the surface of metallic nanoparticles to
prevent them from aggregating. Additionally, for the first time, our results
suggest that resorcinol may act as a reducing agent that can reduce metal salts
to form metal nanoparticles. The core-shell nanoparticles can be carbonized into
M@carbon nanostructures, which have shown great performance in the catalytic
hydrogenation of chlorobenzene. This work not only will help to achieve the
controllable synthesis of noble metal@RF resin and M@carbon core-shell
nanostructures but also will promote research into other RF-based nanostructures
and their catalytic applications.
PMID- 26434609
TI - VRE and VSE Bacteremia Outcomes in the Era of Effective VRE Therapy: A Systematic
Review and Meta-analysis.
AB - BACKGROUND Prior data suggest that vancomycin-resistant Enterococcus (VRE)
bacteremia is associated with worse outcomes than vancomycin-sensitive
Enterococcus (VSE) bacteremia. However, many studies evaluating such outcomes
were conducted prior to the availability of effective VRE therapies. OBJECTIVE To
systematically review VRE and VSE bacteremia outcomes among hospital patients in
the era of effective VRE therapy. METHODS Electronic databases and grey
literature published between January 1997 and December 2014 were searched to
identify all primary research studies comparing outcomes of VRE and VSE
bacteremias among hospital patients, following the availability of effective VRE
therapies. The primary outcome was all-cause, in-hospital mortality, while total
hospital length of stay (LOS) was a secondary outcome. All meta-analyses were
conducted in Review Manager 5.3 using random-effects, inverse variance modeling.
RESULTS Among all the studies reviewed, 12 cohort studies and 1 case control
study met inclusion criteria. Similar study designs were combined in meta
analyses for mortality and LOS. VRE bacteremia was associated with increased
mortality compared with VSE bacteremia among cohort studies (odds ratio [OR],
1.80; 95% confidence interval [CI], 1.38-2.35; I2=0%; n=11); the case-control
study estimate was similar, but not significant (OR, 1.93; 95% CI, 0.97-3.82).
LOS was greater for VRE bacteremia patients than for VSE bacteremia patients
(mean difference, 5.01 days; 95% CI, 0.58-9.44]; I2=0%; n=5). CONCLUSIONS Despite
the availability of effective VRE therapy, VRE bacteremia remains associated with
an increased risk of in-hospital mortality and LOS when compared to VSE
bacteremia. Infect. Control Hosp. Epidemiol. 2015;37(1):26-35.
PMID- 26434610
TI - Current Approaches to the Diagnosis of Classical form of Congenital Adrenal
Hyperplasia.
AB - Congenital adrenal hyperplasia (CAH) is one of the most common diseases
transmitted in an autosomal recessive manner and is caused by mutations of
enzymes which are responsible for the process of adrenal steroidogenesis.
According to the impairment of enzymes involved in steroidogenesis, several types
of CAH can be distinguished. The most common type is associated with mutations in
the CYP21A2 gene, encoding 21-hydroxylase enzyme and has different clinical
forms: Classical (in which there are two types: salt wasting and simple
virilization) and non-classical, characterized by less severe symptoms and late
onset. CAH is characterized by a strong correlation between the genotype and the
phenotype. Mutations in the CYP21A2 gene can cause different degrees of loss of
21-hydroxylase enzyme activity which result in a wide spectrum of clinical
pictures. Several methods used to diagnose CAH (such as determining steroids in
serum or urine) have been known from the 70's. Modern diagnosis of CAH is based
primarily on the use of genetic testing, which is the subject of numerous
constantly updated patents. In this paper the most recent patents on the
diagnosis of CAH were assessed.
PMID- 26434611
TI - Cassia tora Seed Extract and Its Active Compound Aurantio-obtusin Inhibit
Allergic Responses in IgE-Mediated Mast Cells and Anaphylactic Models.
AB - Cassia tora seed is widely used due to its various biological properties
including anticancer, antidiabetic, and anti-inflammatory effects. However, there
has been no report of the effects of C. tora seed extract (CTE) on immunoglobulin
E (IgE)-mediated allergic responses. In this research, we demonstrated the
effects of CTE and its active compound aurantio-obtusin on IgE-sensitized
allergic reactions in mast cells and passive cutaneous anaphylaxis (PCA). CTE and
aurantio-obtusin suppressed degranulation, histamine production, and reactive
oxygen species generation and inhibited the production and mRNA expression of
tumor necrosis factor-alpha and interleukin-4. CTE and aurantio-obtusin also
suppressed the prostaglandin E2 production and expression of cyclooxygenase 2.
Furthermore, CTE and aurantio-obtusin suppressed IgE-mediated FcepsilonRI
signaling such as phosphorylation of Syk, protein kinase CMU, phospholipase
Cgamma, and extracellular signal-regulated kinases. CTE and aurantio-obtusin
blocked mast cell-dependent PCA in IgE-mediated mice. These results suggest that
CTE and aurantio-obtusin are a beneficial treatment for allergy-related diseases.
PMID- 26434612
TI - Decline in the prevalence of anaemia among children of pre-school age after
implementation of wheat flour fortification with multiple micronutrients in
Jordan.
AB - OBJECTIVE: To examine changes in the prevalence of anaemia and its correlates
among children of pre-school age after implementation of wheat flour
fortification with multiple micronutrients in Jordan. DESIGN: Retrospective
analysis of the data from two repeated national cross-sectional panels of pre
school children. SETTING: The two surveys were conducted in 2007 and 2009, 16-20
months and 34-36 months, respectively, after implementation of wheat flour
fortification with multiple micronutrients in Jordan. Anaemia was considered if
Hb level was <11 g/dl. An anaemia prevalence of >=40 % was considered a severe
public health problem, while that of 20-39.9 % was considered a moderate public
health problem. SUBJECTS: A total of 3789 and 3447 children aged 6-59 months
tested in 2007 and 2009, respectively. RESULTS: The prevalence of anaemia in pre
school children declined from 40.4 % in 2007 to 33.9 % in 2009 (adjusted OR=0.74;
P24 months (-13.7 points), children living in urban areas (-8.0 points), children
from rich households (-9.0 points), children who had never been breast-fed (-17.0
points) and well-nourished children (-6.8 points). In both surveys, presence of
childhood anaemia was strongly associated with child age <=24 months, living in
poor households, breast-feeding for >=6 months, malnourishment, poor maternal
education and maternal anaemia. CONCLUSIONS: The public health problem of
childhood anaemia declined from severe in 2007 to moderate in 2009, after the
implementation of wheat flour fortification with multiple micronutrients in
Jordan.
PMID- 26434613
TI - Induction of labor--pharmacology methods.
AB - Pharmacologic methods for induction of labor have been used for many decades.
Pharmacologic agents have an advantage over mechanical methods in that they can
be used during both the initial cervical ripening stage of induction and
throughout the second stage of labor. Pharmacologic induction agents such as
prostaglandins and oxytocin are commonly used for labor and delivery floors and
are well established for use in cervical ripening. Nitric oxide donors and
mifepristone are known agents in medicine but are new and actively studied in the
area of cervical ripening. These agents are introduced and analyzed in this
review.
PMID- 26434614
TI - Intracranial and extracranial arterial dissection presenting with ischemic
stroke: Lesion location and stroke mechanism.
AB - Background and purpose Although cervicocranial artery dissections (CADs) are
common causes of ischemic stroke in young individuals, anatomical locations and
mechanisms of ischemic strokes are still unclear. We evaluate the prevalence,
location, and pathogenic mechanisms of ischemic stroke caused by CADs. METHODS:
We reviewed CAD patients who presented with acute (<7days) ischemic events and
who had undergone diffusion weighted magnetic resonance imaging (MRI) and
appropriate vascular imagings (MR angiography, computed tomography angiography,
digital subtraction angiography, and high-resolution MRI). Stroke mechanisms were
categorized as artery-to-artery (AA) embolism, local branch occlusion, in situ
thrombotic occlusion and hemodynamic impairment. RESULTS: One hundred and thirty
five patients with cerebral infarcts (n=125) or transient ischemic attacks (n=10)
were included. The locations of 159 dissected vessels were: 77 vertebral, 29
internal carotid, 24 middle cerebral, 12 basilar, eight posterior inferior
cerebellar, five anterior cerebral, and four posterior cerebral arteries. Among
stroke mechanisms, A-A embolism (n=70, 55.5%) was the most common followed by
local branch occlusions (n=40, 31.7%) and in situ thrombotic occlusions (n=8,
6.3%). Intracranial CADs were more common (89 vs. 44), less often associated with
trauma (21.3% vs. 40.9%, p=0.018) and A-A embolism (32.9% vs. 97.6%, p<0.001),
and more often treated with intravenous thrombolysis (15.7% vs. 2.3%. p=0.021)
than extracranial CADs. CONCLUSIONS: In our cohort, intracranial CADs are more
common than extracranial CADs, and the vertebral artery is the most frequently
involved site. Although A-A embolism is the main stroke mechanism, local branch
occlusion is another important stroke mechanism.
PMID- 26434615
TI - Chronic kidney disease and intravenous thrombolysis in acute stroke: A systematic
review and meta-analysis.
AB - BACKGROUND: The association between chronic kidney disease (CKD) and hemorrhagic
complications or clinical outcomes in patients treated with intravenous (IV)
thrombolytic agents is controversial. METHODS: We searched multiple databases for
studies on the association between CKD and symptomatic intracerebral hemorrhage
(ICH) and/or clinical outcomes in acute stroke patients treated with IV tissue
plasminogen activator (tPA). Observational studies that evaluated the association
between CKD and outcomes after adjusting for other confounding factors were
eligible. We assessed study quality and performed a meta-analysis. The main
outcome was symptomatic ICH. The secondary outcomes were poor functional status
at 3 months using the modified Rankin Scale, mortality at 3 months, and any ICH.
RESULTS: Seven studies were selected based on our eligibility criteria. Of 7168
patients treated with IV tPA, 2001 (27.9%) had CKD. Patients with CKD had a
higher risk of symptomatic ICH and mortality [pooled odds ratio (OR) 1.56, 95%
confidence interval (CI) 1.05-2.33 and pooled OR 1.70, 95% CI 1.03-2.81,
respectively]. Patients with CKD were likely to have an increased risk of poor
outcome at 3 months. There was no significant association between CKD and any
ICH. CONCLUSIONS: Chronic kidney disease may significantly affect symptomatic
hemorrhagic complications and poor clinical outcomes following administration of
IV tPA.
PMID- 26434616
TI - Transient reduction in venous susceptibility during posterior reversible
encephalopathy syndrome.
AB - We report a case of posterior reversible encephalopathy syndrome (PRES) in which
followed-up MRI demonstrated a transient reduction in venous signal on initial
SWAN images. The progressive normalization of venous signal on D10 and D40
imaging paralleled the progressive decrease of hyperperfusion on CBF images.
Decreased venous susceptibility has never been reported in PRES; it relates most
likely to a transient BOLD effect induced by brain hyperperfusion.
PMID- 26434617
TI - Stabilization of protein-protein interaction complexes through small molecules.
AB - Most of the small molecules that have been identified thus far to modulate
protein-protein interactions (PPIs) are inhibitors. Another promising way to
interfere with PPI-associated biological processes is to promote PPI
stabilization. Even though PPI stabilizers are still scarce, stabilization of
PPIs by small molecules is gaining momentum and offers new pharmacological
options. Therefore, we have performed a literature survey of PPI stabilization
using small molecules. From this, we propose a classification of PPI stabilizers
based on their binding mode and the architecture of the complex to facilitate the
structure-based design of stabilizers.
PMID- 26434618
TI - On a stochastic gene expression with pre-mRNA, mRNA and protein contribution.
AB - In this paper we develop a model of stochastic gene expression, which is an
extension of the model investigated in the paper [T. Lipniacki, P. Paszek, A.
Marciniak-Czochra, A.R. Brasier, M. Kimmel, Transcriptional stochasticity in gene
expression, J. Theor. Biol. 238 (2006) 348-367]. In our model, stochastic effects
still originate from random fluctuations in gene activity status, but we precede
mRNA production by the formation of pre-mRNA, which enriches classical
transcription phase. We obtain a stochastically regulated system of ordinary
differential equations (ODEs) describing evolution of pre-mRNA, mRNA and protein
levels. We perform mathematical analysis of a long-time behavior of this
stochastic process, identified as a piece-wise deterministic Markov process
(PDMP). We check exact results using numerical simulations for the distributions
of all three types of particles. Moreover, we investigate the deterministic
(adiabatic) limit state of the process, when depending on parameters it can
exhibit two specific types of behavior: bistability and the existence of the
limit cycle. The latter one is not present when only two kinds of gene expression
products are considered.
PMID- 26434619
TI - Transition from grant funding to a self-supporting burn telemedicine program in
the western United States.
AB - BACKGROUND: Many Americans have limited access to specialty burn care, and
telemedicine has been proposed as a means to address this disparity. However,
many telemedicine programs have been founded on grant support and then fail once
the grant support expires. Our objective was to demonstrate that a burn
telemedicine program can be financially viable. METHODS: This retrospective
review from 2005 to 2014 evaluated burn telemedicine visits and financial
reimbursement during and after a Technology Opportunities Program grant to a
regional burn center. RESULTS: In 2005, we had 12 telemedicine visits, which
increased to 458 in 2014. In terms of how this compares to in-person clinic
visits, we saw a consistent increase in telemedicine visits as a percentage of
total clinic visits from .26% in 2005 to 14% in 2014. Median telemedicine
reimbursement has been equivalent to in-person visits. CONCLUSIONS: Specialty
telemedicine programs can successfully transition from grant-funded enterprises
to self-sustaining. The availability of telemedicine services allows access to
specialty expertise in a large and sparsely populated region without imposing an
undue financial burden.
PMID- 26434620
TI - A novel junctional adhesion molecule A (CgJAM-A-L) from oyster (Crassostrea
gigas) functions as pattern recognition receptor and opsonin.
AB - Junctional adhesion molecule (JAM), a subfamily of immunoglobulin superfamily
(IgSF) with a couple of immunoglobulin domains, can act as regulator in
homeostasis and inflammation of vertebrates. In the present study, a structural
homolog of JAM-A (designated CgJAM-A-L) was screened out from oyster, Crassostrea
gigas, through a search of JAM-A D1 domain (N-terminal Ig domain in JAM-A). The
cDNA of CgJAM-A-L was of 1188 bp encoding a predicted polypeptide of 395 amino
acids. The immunoreactive area of CgJAM-A-L mainly distributed over the plasma
membrane of hemocytes. After Vibro splendidus or tumor necrosis factor (CgTNF-1)
stimulation, the mRNA transcripts of CgJAM-A-L in hemocytes increased
significantly by 4.46-fold and 9.00-fold (p < 0.01) of those in control group,
respectively. The recombinant CgJAM-A-L protein (rCgJAM-A-L) could bind multiple
PAMPs including lipopolysaccharides (LPS), peptidoglycan (PGN), lipoteichoic acid
(LTA), mannose (MAN), beta-glucan (GLU) and poly(I:C), and various microorganisms
including Micrococcus luteus, Staphylococcus aureus, Escherichia coli, Vibro
anguillarum, V. splendidus, Pastoris pastoris and Yarrowia lipolytica. The
phagocytic rates of oyster hemocytes towards Gram-negative bacteria V.
anguillarum and yeast P. pastoris were significantly enhanced after the
incubation of rCgJAM-A-L, and even increased more significantly after the pre
incubation of rCgJAM-A-L with microbes (p < 0.01). The results collectively
indicated that CgJAM-A-L functioned as an important pattern recognition receptor
(PRR) and opsonin in the immune defense against invading pathogen in oyster.
Moreover, as the most primitive specie with homolog of JAMs, the information of
CgJAM-A-L in oyster would provide useful clues for the evolutionary study of JAMs
and immunoglobulins.
PMID- 26434621
TI - Chronic glucocorticoids exposure enhances neurodegeneration in the frontal cortex
and hippocampus via NLRP-1 inflammasome activation in male mice.
AB - Neuroinflammation plays an important role in the pathogenesis of
neurodegenerative diseases, such as Alzheimer's disease (AD) and depression.
Chronic glucocorticoids (GCs) exposure has deleterious effects on the structure
and function of neurons and is associated with development and progression of AD.
However, little is known about the proinflammatory effects of chronic GCs
exposure on neurodegeneration in brain. Therefore, the aim of this study was to
evaluate the effects of chronic dexamethasone (DEX) treatment (5mg/kg, s.c. for
7, 14, 21 and 28 days) on behavior, neurodegeneration and neuroinflammatory
parameters of nucleotide-binding oligomerization domain-like receptor pyrin
domain-containing 1 (NLRP-1) inflammasome in male mice. The results showed that
DEX treatment for 21 and 28 days significantly reduced the spontaneous motor
activity and exploratory behavior of the mice. In addition, these mice showed
significant neurodegeneration and a decrease of microtubule-associated protein 2
(MAP2) in the frontal cortex and hippocampus CA3. DEX treatment for 7, 14, 21 and
28 days significantly decreased the mRNA and protein expression of glucocorticoid
receptor (GR). Moreover, DEX treatment for 21 and 28 days significantly increased
the proteins expression of NLRP-1, Caspase-1, Caspase-5, apoptosis associated
speck-like protein (ASC), nuclear factor-kappaB (NF-kappaB), p-NF-kappaB,
interleukin-1beta (IL-1beta), IL-18 and IL-6 in the frontal cortex and
hippocampus brain tissue. DEX treatment for 28 days also significantly increased
the mRNA expression levels of NLRP-1, Caspase-1, ASC and IL-1beta. These results
suggest that chronic GCs exposure may increase brain inflammation via NLRP-1
inflammasome activation and induce neurodegeneration.
PMID- 26434622
TI - The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub
populations of rat trigeminal ganglion sensory neurons.
AB - The recent discovery that mammalian nociceptors express Toll-like receptors
(TLRs) has raised the possibility that these cells directly detect and respond to
pathogens with implications for either direct nociceptor activation or
sensitization. A range of neuronal TLRs have been identified, however a detailed
description regarding the distribution of expression of these receptors within
sub-populations of sensory neurons is lacking. There is also some debate as to
the composition of the TLR4 receptor complex on sensory neurons. Here we use a
range of techniques to quantify the expression of TLR4, TLR7 and some associated
molecules within neurochemically-identified sub-populations of trigeminal (TG)
and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of
expression and co-expression of two isoforms of lysophosphatidylcholine
acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be
involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within
sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7
preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1)
and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of
nociceptor populations, within both TG and DRG. A gene expression profile shows
that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is
expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2
immunostaining is absent from neuronal profiles within both TG and DRG and is
confined to non-neuronal cell types under naive conditions. Together, our results
show that nociceptors express the molecular machinery required to directly
respond to pathogenic challenge independently from the innate immune system.
PMID- 26434623
TI - Task-specific stability of abundant systems: Structure of variance and motor
equivalence.
AB - Our main goal was to test a hypothesis that transient changes in performance of a
steady-state task would result in motor equivalence. We also estimated effects of
visual feedback on the amount of reorganization of motor elements. Healthy
subjects performed two variations of a four-finger pressing task requiring
accurate production of total pressing force (F TOT) and total moment of force (M
TOT). In the Jumping-Target task, a sequence of target jumps required transient
changes in either F TOT or M TOT. In the Step-Perturbation task, the index finger
was lifted by 1cm for 0.5s leading to a change in both F TOT and M TOT. Visual
feedback could have been frozen for one of these two variables in both tasks.
Deviations in the space of finger modes (hypothetical commands to individual
fingers) were quantified in directions of unchanged F TOT and M TOT (motor
equivalent - ME) and in directions that changed F TOT and M TOT (non-motor
equivalence - nME). Both the ME and nME components increased when the performance
changed. After transient target jumps leading to the same combination of F TOT
and M TOT, the changes in finger modes had a large residual ME component with
only a very small nME component. Without visual feedback, an increase in the nME
component was observed without consistent changes in the ME component. Results
from the Step-Perturbation task were qualitatively similar. These findings
suggest that both external perturbations and purposeful changes in performance
trigger a reorganization of elements of an abundant system, leading to large ME
change. These results are consistent with the principle of motor abundance
corroborating the idea that a family of solutions is facilitated to stabilize
values of important performance variables.
PMID- 26434625
TI - Altered crosstalk in the dipeptidyl peptidase-4-incretin-immune system in type 1
diabetes: A hypothesis generating pilot study.
AB - Both GLP1(7)(-)(36) (via GLP1 receptor) and the dipeptidyl peptidase-4 (DPP4)
cleaved form of GLP1 (GLP1(9)(-)(36), independently of GLP1R) may modulate the
response of lymphocytes to cytokine stimuli. The incretin axis, CXCR3 (receptor
of DPP4 ligand cytokines CXCL9-11) expression on T(reg)s and hematologic
parameters were assessed in 34 patients with long standing type 1 diabetes (T1DM)
and in 35 healthy controls. Serum DPP4 (sDPP4) activity, plasma total GLP1 and
GLP1(7)(-)(36) concentrations were determined. GLP1(9)(-)(36) concentrations were
calculated. CXCR3 expression (flow cytometry) was higher on the CD25(
/)(low)Foxp3(+) than on the CD25(+)Foxp3(+) T(reg)s independently from T1DM,
suggesting that CD25(-/)(low)Foxp3(+) T(reg)s are possibly waiting for
orientational chemotactic stimuli in a "standby mode". The higher sDPP4
activities in T1DM were inversely correlated with GLP1(7)(-)(36) levels and
GLP1(9)(-)(36) levels directly with lymphocyte counts in controls. Our results
might indicate an altered DPP4-incretin system and altered immunoregulation
including a potentially dysfunctional GLP1(9)(-)(36) signaling in T1DM.
PMID- 26434626
TI - Analysis of distinct molecular assembly complexes of keratin K8 and K18 by
hydrogen-deuterium exchange.
AB - Keratins are intermediate filament (IF) proteins that form complex filament
systems in epithelial cells, thus serving as scaffolding elements and mechanical
stress absorbers. The building blocks of keratin IFs are parallel coiled-coil
dimers of two distinct sequence-related proteins distinguished as type I and type
II keratins. To gain more insight into their structural dynamics, we resorted to
hydrogen-deuterium exchange mass spectrometry of keratins K8 and K18, which are
characteristic for simple epithelial cells. Using this powerful technique not
employed with IFs before, we mapped patterns of protected versus unprotected
regions in keratin complexes at various assembly levels. In particular, we
localized protein segments exhibiting different hydrogen exchange patterns in
tetramers versus filaments. We observed a general pattern of precisely positioned
regions of stability intertwining with flexible regions, mostly represented by
the non-alpha-helical segments. Notably, some regions within the coiled-coil
domains are significantly more dynamic than others, while the IF-consensus motifs
at the end domains of the central alpha-helical "rod" segment, which mediate the
"head-to-tail" dimer-dimer interaction in the filament elongation process, become
distinctly more protected upon formation of filaments. Moreover, to gain more
insight into the dynamics of the individual keratins, we investigated the
properties of homomeric preparations of K8 and K18. The physiological importance
of keratins without a partner is encountered in both pathological and
experimental situations when one of the two species is present in robust excess
or completely absent, such as in gene-targeted mice.
PMID- 26434627
TI - Reward Processing, Functional Connectivity, Psychopathy, and Research Domain
Criteria.
PMID- 26434628
TI - Dysfunctional Connectivity in the Depressed Adolescent Brain.
PMID- 26434629
TI - Consequences of Adolescent Smoking: Cognitive Performance, Brain Function, and
Policy Implications.
PMID- 26434624
TI - Influence of maternal thyroid hormones during gestation on fetal brain
development.
AB - Thyroid hormones (THs) play an obligatory role in many fundamental processes
underlying brain development and maturation. The developing embryo/fetus is
dependent on maternal supply of TH. The fetal thyroid gland does not commence TH
synthesis until mid gestation, and the adverse consequences of severe maternal TH
deficiency on offspring neurodevelopment are well established. Recent evidence
suggests that even more moderate forms of maternal thyroid dysfunction,
particularly during early gestation, may have a long-lasting influence on child
cognitive development and risk of neurodevelopmental disorders. Moreover, these
observed alterations appear to be largely irreversible after birth. It is,
therefore, important to gain a better understanding of the role of maternal
thyroid dysfunction on offspring neurodevelopment in terms of the nature,
magnitude, time-specificity, and context-specificity of its effects. With respect
to the issue of context specificity, it is possible that maternal stress and
stress-related biological processes during pregnancy may modulate maternal
thyroid function. The possibility of an interaction between the thyroid and
stress systems in the context of fetal brain development has, however, not been
addressed to date. We begin this review with a brief overview of TH biology
during pregnancy and a summary of the literature on its effect on the developing
brain. Next, we consider and discuss whether and how processes related to
maternal stress and stress biology may interact with and modify the effects of
maternal thyroid function on offspring brain development. We synthesize several
research areas and identify important knowledge gaps that may warrant further
study. The scientific and public health relevance of this review relates to
achieving a better understanding of the timing, mechanisms and contexts of
thyroid programing of brain development, with implications for early
identification of risk, primary prevention and intervention.
PMID- 26434630
TI - Overexpression of the chemokine receptor CXCR3 and its correlation with favorable
prognosis in gastric cancer.
AB - Chemokine receptor, CXCR3, has been increasingly reported to be involved in
tumorigenesis and tumor progression, but limited data are available regarding the
expression of CXCR3 in gastric cancer (GC). In the present study, the expressions
of CXCR3 and its variants were detected in 96 GC and corresponding nontumor
gastric tissues by immunohistochemical staining, in 40 freshly frozen GC and
nontumor gastric tissues by reverse-transcription polymerase chain reaction and
quantitative real-time polymerase chain reaction, and in 10 freshly frozen GC and
nontumor gastric tissues by Western blotting. Results revealed that an
overexpression of CXCR3 occurs in GC tissues as compared to the nontumor gastric
tissues. High level of CXCR3 expression was found to be inversely associated with
invasion depth and metastasis (P = .030 and P = .019, respectively) and directly
associated with improved overall survival (log-rank test, P < .001). Furthermore,
multivariate analysis showed that high CXCR3 expression acts an independent
prognostic factor for GC patients (hazard ratio, 0.379 [0.196-0.734]; P = .004).
The messenger RNA expression of both the CXCR3 variants, CXCR3-A and CXCR3-B,
were up-regulated in GC tissues (P = .006 and P = .002, respectively), although
CXCR3-B messenger RNA expression was significantly higher than CXCR3-A, with an
average CXCR3-B to CXCR3-A ratio of 1.80. CXCR3-B protein expression was also up
regulated in GC tissues (P = .023). In conclusion, our study suggested a
potential use of CXCR3 overexpression as a prognostic marker for GC and
involvement of the up-regulation of CXCR3-B in favorable prognosis of GC
patients.
PMID- 26434631
TI - Molecular characteristics of colorectal neuroendocrine carcinoma; similarities
with adenocarcinoma rather than neuroendocrine tumor.
AB - To further clarify the molecular features of colorectal neuroendocrine carcinomas
(NECs), we immunohistochemically examined tumor samples from 25 NECs, including 9
small cell NECs (SCNECs) and 16 large cell NECs (LCNECs), 20 neuroendocrine
tumors (NETs), and 21 poorly differentiated adenocarcinomas (PDCs) for the
expression of several biomarkers (p53, beta-catenin, Bcl-2, Rb, p16, p21, cyclin
D1, and cyclin E) and used sequencing analysis to identify gene alterations of
TP53, APC, CTNNB1, KRAS, and BRAF. The frequencies of aberrant p53 expression
(88%), beta-catenin nuclear expression (48%), and high expression of cyclin E
(84%) were significantly higher in NECs than in NETs (0%, 5%, and 5%, P < .01,
respectively). The immunohistochemical results of NECs and PDCs were similar.
TP53, APC, KRAS, and BRAF gene mutations were variously detected in NECs and PDCs
but not in any NETs. The frequencies of decreased expression of Rb (56%) and high
expression of p16 (56%) and Bcl-2 (64%) were significantly higher in NECs than in
PDCs (5%, 19%, and 5%, P < .05, respectively) or NETs (10%, 5%, and 5%, P < .01,
respectively). Such immunohistochemical characteristics of NECs were more evident
in SCNECs than in large cell NECs (P < .01). In conclusion, the molecular
features of colorectal NECs are similar to those of adenocarcinomas and not to
those of NETs. Decreased expression of Rb and high expression of p16 and Bcl-2
are characteristics of NECs, suggesting that Rb-p16 pathway disruption may
contribute to the promotion of proliferative activity in colorectal NECs. SCNECs
may be a prototype of NECs.
PMID- 26434632
TI - Self-selecting homochiral quadruple-stranded helicates and control of
supramolecular chirality.
AB - Enantiomeric M4L4 helical cages have been prepared whose supramolecular chirality
is induced by the chemical chirality of the self-sorting amino acid-derived
ligands that are used. Using scrambled diastereomeric ligands or achiral glycine
derived ligands yields analogous complexes yet 'turns off' the supramolecular
chirality by producing centrosymmetric cages.
PMID- 26434633
TI - Nitronyl nitroxide based 2p-3d-4f chains with the magnetocaloric effect and slow
magnetic relaxation.
AB - Four new nitronyl nitroxide radical based hetero-tri-spin one-dimensional
compounds, namely [{Ln(hfac)3}3{Cu(hfac)2}{NIT-Ph(OMe)2}4]n (Ln = Gd (1), Tb (2),
Dy (3), Er (4); hfac = hexafluoroacetylacetonate; NIT-Ph(OMe)2 = 2-(2',4'
dimethoxyphenyl)-4,4,5,5-tetramethyl-imidazolyl-1-oxyl-3-oxide) have been
successfully prepared. Single crystal X-ray crystallographic analysis reveals
that complexes 1-4 possess a 1D chain structure with a repeating [Cu-Rad-Ln-Rad
Ln-Rad-Ln-Rad] moiety in which Ln(hfac)3 and Cu(hfac)2 units are bridged by
nitronyl nitroxide radicals through the NO groups. DC magnetic studies found that
ferromagnetic interactions between metals and the coordinated NO groups are
active in all four compounds. The Tb derivative displays frequency dependent ac
magnetic susceptibilities, indicating slow magnetic relaxation behavior. The Gd
complex shows an important cryogenic magnetocaloric effect with the entropy
change (-DeltaSm) of 13.5 J kg(-1) K(-1) at 2 K and a magnetic field of 7 T,
representing the first example of Gd-radical molecular species exhibiting the
magnetocaloric effect.
PMID- 26434634
TI - Backbone circularization of Bacillus subtilis family 11 xylanase increases its
thermostability and its resistance against aggregation.
AB - The activity of proteins is dictated by their three-dimensional structure, the
native state, and is influenced by their ability to remain in or return to the
folded native state under physiological conditions. Backbone circularization is
thought to increase protein stability by decreasing the conformational entropy in
the unfolded state. A positive effect of circularization on stability has been
shown for several proteins. Here, we report the development of a cloning standard
that facilitates implementing the SICLOPPS technology to circularize proteins of
interest using split inteins. To exemplify the usage of the cloning standard we
constructed two circularization vectors based on the Npu DnaE and gp41-1 split
inteins, respectively. We use these vectors to overexpress in Escherichia coli
circular forms of the Bacillus subtilis enzyme family 11 xylanase that differ in
the identity and number of additional amino acids used for circularization
(exteins). We found that the variant circularized with only one additional serine
has increased thermostability of 7 degrees C compared to native xylanase. The
variant circularized with six additional amino acids has only a mild increase in
thermostability compared to the corresponding exteins-bearing linear xylanase,
but is less stable than native xylanase. However, this circular xylanase retains
more than 50% of its activity after heat shock at elevated temperatures, while
native xylanase and the corresponding exteins-bearing linear xylanase are largely
inactivated. We correlate this residual activity to the fewer protein aggregates
found in the test tubes of circular xylanase after heat shock, suggesting that
circularization protects the protein from aggregation under these conditions.
Taken together, these data indicate that backbone circularization has a positive
effect on xylanase and can lead to increased thermostability, provided the
appropriate exteins are selected. We believe that our cloning standard and
circularization vectors will facilitate testing the effects of circularization on
other proteins.
PMID- 26434636
TI - The synthesis and structure of a carbene-stabilized iminocarboranyl-boron(I)
compound.
AB - A carbene-stabilized iminocarboranylboron(I) compound has been synthesized and
structurally characterized. Single-crystal X-ray analyses and DFT calculations
show that the pi back donation of the lone pair of electrons on the boron(I)
center onto the pi* orbital of the imine unit is crucial for removing the
electron density of the boron center thereby stabilizing such species, in which
the carbene serves solely as a sigma donor. This work also demonstrates that
imines play a similar role to that of carbenes in the stabilization of low valent
boron compounds.
PMID- 26434637
TI - Microstructure and rheology of microfibril-polymer networks.
AB - By using an adsorbing polymer in combination with mechanical de-agglomeration,
the microstructure and rheological properties of networks of microfibrils could
be controlled. By the addition of sodium carboxymethyl cellulose during de
agglomeration of networks of bacterial cellulose, the microstructure could be
changed from an inhomogeneous network with bundles of microfibrils and voids to a
more homogeneous spread and alignment of the particles. As a result the
macroscopic rheological properties were altered. Although still elastic and gel
like in nature, the elasticity and viscous behavior of the network as a function
of microfibril concentration is altered. The microstructure is thus changed by
changing the surface properties of the building blocks leading to a direct
influence on the materials macroscopic behavior.
PMID- 26434635
TI - Cerebrospinal fluid levels of IL-6 are decreased and correlate with cognitive
status in DLB patients.
AB - INTRODUCTION: Inflammatory processes have previously been shown to influence
cognition and progression of dementia. An involvement of interleukin (IL)-6 has
in particular been suggested as altered levels of IL-6 in cerebrospinal fluid
(CSF) have been found in patients with Alzheimer's disease (AD). Also, an
association between cognitive decline and levels of IL-6 in CSF have been
reported. The aim of the present study was to investigate whether patients
clinically diagnosed with dementia with Lewy bodies (DLB) display altered CSF IL
6 levels in comparison with patients with AD and control subjects without
dementia and whether the IL-6 levels are correlated with cognitive status and
biomarkers for AD and synucleinopathy. METHODS: To analyse CSF of patients with
AD (n = 45), patients with DLB (n = 29) and control subjects without dementia (n
= 36), we used immunoassays to measure levels of IL-6 (multiplex
electrochemiluminescence); AD markers phosphorylated tau, total tau and amyloid
beta1-42 (enzyme-linked immunosorbent assay [ELISA]); and alpha-synuclein
(ELISA). Cognitive status was evaluated using the Mini Mental State Examination
(MMSE). RESULTS: Our analysis showed significantly lower levels of IL-6 in CSF
from patients with DLB than in CSF from patients with AD and control subjects
without dementia. The IL-6 levels were also negatively correlated with MMSE and
positively correlated with alpha-synuclein CSF levels. CONCLUSIONS: Our findings
support previous studies by demonstrating a link between inflammatory processes
and dementia progression and further strengthen the hypothesis that IL-6 is
involved in dementia pathology and cognitive decline.
PMID- 26434638
TI - Gas sorption in solid surfaces: a computational study using rigid and Einstein
solid models.
AB - The reactive Monte Carlo (RxMC) method was proposed to describe the sorption of
gases in solid materials due to the chemical reaction A + B ? C. Two models were
used to simulate the solid; the first model considered simulations with rigid
particles in the solid whereas in the second model the particles were allowed to
vibrate inside the solid with a given spring constant, i.e. an Einstein solid was
used to simulate the substrate. In both models not only physisorption but also
chemisorption of the fluid was observed. Sorption curves, at different spring
constants, were simulated and it was noted that sorption was always enhanced with
the Einstein solid model. Moreover, an inverse dependent function of the spring
constant with the temperature was found. Finally, the second model might be used
to explain the unusual sorption behavior observed in actual experimental
reactions such as CO2 + Li2O ? Li2CO3.
PMID- 26434639
TI - Solid phase polymerization of phenylenediamine toward a self-supported FeN(x)/C
catalyst with high oxygen reduction activity.
AB - Solid phase polymerization of phenylenediamine with a template toward a self
supported FeNx/C catalyst was introduced. Using ZnO nanoparticles as the hard
template could increase the surface area of the catalyst, thus the oxygen
reduction activity was radically enhanced, to 21.9 A g(-1) at 0.80 V (vs. RHE) in
acid medium.
PMID- 26434640
TI - Synthesis and Structural Reassignment of Plakinidone.
AB - In connection with its first synthesis, plakinidone was structurally revised to a
five-membered lactone. The key evidence for the previous assignment of this
natural product as a perlactone was proven to be a misinterpretation of the MS
data because of unawareness of a facile air oxidation. The synthetic samples also
allowed for detection of differences in (13)C NMR for diastereomers of remote
stereogenic centers, along with the influence of the air oxidation on the optical
rotation.
PMID- 26434641
TI - Novel Cardioprotective Agents: Fact or Fiction?
PMID- 26434642
TI - Interview with Ira Lurie.
PMID- 26434643
TI - Polypharmacology Shakes Hands with Complex Aetiopathology.
AB - Chronic diseases are due to deviations of fundamental physiological systems, with
different pathologies being characterised by similar malfunctioning biological
networks. The ensuing compensatory mechanisms may weaken the body's dynamic
ability to respond to further insults and reduce the efficacy of conventional
single target treatments. The multitarget, systemic, and prohomeostatic actions
emerging for plant cannabinoids exemplify what might be needed for future
medicines. Indeed, two combined cannabis extracts were approved as a single
medicine (Sativex((r))), while pure cannabidiol, a multitarget cannabinoid, is
emerging as a treatment for paediatric drug-resistant epilepsy. Using emerging
cannabinoid medicines as an example, we revisit the concept of polypharmacology
and describe a new empirical model, the 'therapeutic handshake', to predict
efficacy/safety of compound combinations of either natural or synthetic origin.
PMID- 26434645
TI - Bone response to collagenized xenografts of porcine origin (mp3((r)) ) and a
bovine bone mineral grafting (4BONE(TM) XBM) grafts in tibia defects:
experimental study in rabbits.
AB - OBJECTIVES: This study aimed to carry out the evaluation of bone response of new
bone formation to two different xenografts (bovine and porcine) biomaterials
inserted in rabbit tibiae. MATERIALS AND METHODS: The study used a total of 20
male New Zealand albino rabbits. They received a total of 40 grafts in the
proximal metaphyseal areas of both tibiae. Two biomaterials were evaluated: 20
porcine xenografts, as a bone granulate (OsteoBiol((r)) MP3((r)) ; Tecnoss srl,
Giaveno, Italy), were placed in the proximal metaphyseal area of the right tibia,
20 anorganic bovine bone mineral grafting (4BONE(TM) XBM, MIS Implants Inc.,
BARLEV, Israel) were placed in the left tibia. Following graft insertion, the
animals were sacrificed in two groups of 10 animals, after 1 and 4 months,
respectively. For each group, biomaterials were analyzed: newly formed bone,
residual graft materials and the connective tissue. Histomorphometric, EDX
analysis and element mapping were performed at 1 and 4 months after graft
insertion. RESULTS: At 4 months after treatment, the bone defects displayed
radiological images that showed complete repair of osseous defects.
Histomorphometric evaluation showed that for the porcine xenograft, the study
averages for newly formed bone represented 84.23 +/- 2.9%, while bovine matrix
was 79.34 +/- 2.1%. For residual graft material, the porcine biomaterial had
11.23 +/- 1.7% and the bovine graft 31.56 +/- 2.3%. Finally, the connective
tissue for MP3 was 10.33 +/- 1.8%, while for the 4BONE(TM) XBM we obtained 14.34
+/- 2.9%. Element analysis revealed higher percentages of Ca (54 +/- 9%) and P
(35 +/- 6%) in the group B than group A and control group (P < 0.05).
CONCLUSIONS: Defects of a critical size in a rabbit tibia model can be sealed
using a bovine porous biphasic calcium phosphate and MP3 material; this supports
new bone formation, creates a bridge between borders, and facilitates bone
ingrowth in both biomaterials. Furthermore, this study observed partial
dissolution of the mineral phase of four bone graft and complete resorption of
porcine MP3 biomaterial and its incorporation into the surrounding bone.
Depending on clinical needs, each biomaterial could be useful in daily clinical
practice.
PMID- 26434644
TI - Pharmacological Modulation of the N-End Rule Pathway and Its Therapeutic
Implications.
AB - The N-end rule pathway is a proteolytic system in which single N-terminal amino
acids of short-lived substrates determine their metabolic half-lives. Substrates
of this pathway have been implicated in the pathogenesis of many diseases,
including malignancies, neurodegeneration, and cardiovascular disorders. This
review provides a comprehensive overview of current knowledge about the mechanism
and functions of the N-end rule pathway. Pharmacological strategies for the
modulation of target substrate degradation are also reviewed, with emphasis on
their in vivo implications. Given the rapid advances in structural and
biochemical understanding of the recognition components (N-recognins) of the N
end rule pathway, small-molecule inhibitors and activating ligands of N-recognins
emerge as therapeutic agents with novel mechanisms of action.
PMID- 26434646
TI - Contraceptive care at the time of medical abortion: experiences of women and
health professionals in a hospital or community sexual and reproductive health
context.
AB - OBJECTIVE: To examine experiences of contraceptive care from the perspective of
health professionals and women seeking abortion, in the contexts of hospital
gynaecology departments and a specialist sexual and reproductive health centre
(SRHC). MATERIALS AND METHODS: We conducted in-depth semistructured interviews
with 46 women who had received contraceptive care at the time of medical abortion
(gestation <=9weeks) from one SRHC and two hospital gynaecology-department-based
abortion clinics in Scotland. We also interviewed 25 health professionals (nurses
and doctors) involved in abortion and contraceptive care at the same research
sites. We analysed interview data thematically using an approach informed by the
Framework method, and comparison was made between the two clinical contexts.
RESULTS: Most women and health professionals felt that contraceptive counselling
at abortion was acceptable and appropriate, if provided in a sensitive,
nonjudgmental way. Participants framed contraceptive provision at abortion as
significant primarily as a means of preventing subsequent unintended conceptions.
Accounts of contraceptive decision making also presented tensions between the
priorities of women and health professionals, around 'manoeuvring' women towards
contraceptive uptake. Comparison between clinical contexts suggests that women's
experiences may have been more positive in the SRHC setting. CONCLUSIONS: Whilst
abortion may be a theoretically and practically convenient time to address
contraception, it is by no means an easy time to do so and requires considerable
effort and expertise to be managed effectively. Training for those providing
contraceptive care at abortion should explicitly address potential conflicts
between the priorities of health professionals and women seeking abortion.
IMPLICATIONS: This paper offers unique insight into the detail of women and
health professionals' experiences of addressing contraception at the time of
medical abortion. The comparison between hospital and community SRHC contexts
highlights best practise and areas for improvement relevant to a range of
settings.
PMID- 26434647
TI - Anti-Arthritic and Antiinflammatory Effects of the Traditional Uighur Formula
Kursi Caper In Vivo.
AB - Kursi Caper (KC) is a Uighur medicine based on caper which is widely used to
treat arthritis and rheumatism, and preliminary studies in our laboratory showed
that this traditional formula may possess potent antiinflammatory effects. This
study confirms the antiinflammatory effect of KC in the adjuvant induced
arthritis (AIA) model, the carrageenan and cotton-pellet induced granuloma rat
models, and further investigates in vivo the mechanism of action by measuring
relevant indicators of anti-arthritic activity. KC showed significant and dose
dependent anti-arthritic and antiinflammatory effects, demonstrated by reduced
paw edema and arthritic scores in all animal models. Histopathological
examination showed that KC reduced levels of synovial inflammatory factors in AIA
rats. The overproduction of TNF-alpha and IL-1beta was attenuated, and CAT, MDA
and SOD levels were restored to normal in KC-treated rats. KC also significantly
reduced LPS-induced proliferation of B lymphocytes and ConA induced proliferation
of T lymphocytes in a dose-dependent manner. Flow cytometry showed that the high
dose KC-treated group had a significantly decreased frequency of Th17 cells. This
study indicates that KC can significantly attenuate arthritis and inflammation in
rats by decreasing the levels of inflammatory cytokines, regulating oxidative
stress, reducing lymphocyte proliferation and decreasing Th17. This supports the
traditional use of KC as a potential modern therapeutic agent for the treatment
of arthritis and related conditions.
PMID- 26434648
TI - Preface for small-molecule activation: from biological principles to energy
applications. part 2: small molecules related to the global nitrogen cycle.
PMID- 26434649
TI - Centile estimation for a proportion response variable.
AB - This paper introduces two general models for computing centiles when the response
variable Y can take values between 0 and 1, inclusive of 0 or 1. The models
developed are more flexible alternatives to the beta inflated distribution. The
first proposed model employs a flexible four parameter logit skew Student t
(logitSST) distribution to model the response variable Y on the unit interval (0,
1), excluding 0 and 1. This model is then extended to the inflated logitSST
distribution for Y on the unit interval, including 1. The second model developed
in this paper is a generalised Tobit model for Y on the unit interval, including
1. Applying these two models to (1-Y) rather than Y enables modelling of Y on the
unit interval including 0 rather than 1. An application of the new models to real
data shows that they can provide superior fits.
PMID- 26434650
TI - The influence of various rehydration protocols on biomechanical properties of
different acellular tissue matrices.
AB - OBJECTIVES: This study evaluated the influence of different rehydration media and
time periods on biomechanical and structural properties of different acellular
collagen matrices (ACMs). MATERIALS AND METHODS: Specimens of three ACMs
(mucoderm(r), Mucograft(r), Dynamatrix(r)) were rehydrated in saline solution
(SS) or human blood for different time periods (5-60 min). ACMs under dry
condition served as controls. Biomechanical properties of the ACMs after
different rehydration periods were determined by means of tensile testing. ACMs'
properties were further characterized using Fourier-transform-infrared
spectroscopy (FTIR) and differential scanning calorimetry (DSC). RESULTS: At dry
conditions, mucoderm(r) presented the highest tensile strength (TS) and
Dynamatrix(r) showed the maximum elastic modulus (EM; p each <=0.036).
Rehydration in SS and blood resulted in significant TS changes of mucoderm(r) (p
each <=0.05). Concering EM, mucograft(r) showed significantly decreased values
after rehydration in SS compared to Dynamatrix(r) and mucoderm(r) after 10 min (p
each <=0.024). mucoderm(r) hydrated for 5 min in blood displayed nearly double TS
and a significantly increased EM after 60 min (p = 0.043) compared to rehydration
in SS. TS and EM values of Dynamatrix(r) and Mucograft(r) were not altered
following rehydration in blood versus SS (p each >=0.053). FTIR analysis
confirmed the recovery of the graft protein backbone with increased rehydration
in all samples. DSC measurements revealed that tissue hydration decreased thermal
stability of the investigated ACMs. CONCLUSION: Our findings demonstrated that
the rehydration protocol affects the biomechanical properties of ACMs. CLINICAL
RELEVANCE: Clinicians should be aware of altered handling and mechanical
properties of ACMs following different rehydration protocols.
PMID- 26434651
TI - Effects of periodontal therapy on serum lipid profile and proinflammatory
cytokines in patients with hyperlipidemia: a randomized controlled trial.
AB - OBJECTIVE: The aim of this study was to evaluate whether periodontal treatment in
patients with periodontitis and hyperlipidemia may have any influence on plasma
lipids and pro-inflammatory cytokine levels. MATERIAL AND METHODS: We randomly
assigned 109 patients with hyperlipidemia and chronic periodontitis into group 1
(n = 55) and group 2 (n = 54). Patients in group 1 underwent a standard cycle of
supragingival mechanical scaling and polishing. Patients in group 2 underwent the
adjunctive full-mouth intensive removal of subgingival dental plaque biofilms
with the use of scaling and root planning. Periodontal parameters, total
cholesterol (TC), triglyceride (TRG), high-density lipoprotein cholesterol (HDL
C), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-alpha (TNF
alpha), interleukin(IL)-1beta(IL-1beta), and IL-6 were evaluated before treatment
and 2 and 6 months after treatment. RESULTS: Two and 6 months after treatment,
TRG levels were significantly lower in group 2 than in group 1 (P < 0.05), and
the levels of HDL-C were significantly higher (P < 0.05). Two and 6 months after
therapy, the levels of TNF-alpha were significantly lower in group 2 than in
group 1 (P < 0.05), as were the levels of IL-1beta (P < 0.001) and IL-6 (P <
0.001). CONCLUSIONS: Intensive periodontal treatment of participants with
hyperlipidemia and chronic periodontitis improved serum lipid levels and
decreased circulating pro-inflammatory cytokine levels. CLINICAL RELEVANCE: This
study showed that intensive treatment of periodontitis results in an improvement
in serum lipid levels and a decrease in serum proinflammatory cytokine levels in
patients with periodontitis and hyperlipidemia. These findings may contribute to
present knowledge that periodontal therapy may be beneficial for individuals with
hyperlipidemia.
PMID- 26434652
TI - Investigation of dental materials as skin simulants for forensic skin/skull/brain
model impact testing.
AB - PURPOSE: The purpose of this study was to measure the tear strength and hardness
of four different dental silicones in comparison to that of porcine skin.
METHODS: Specimens were prepared (n = 20/group) according to ASTM D624-00, using
three hydrophilic vinyl polysiloxane impression materials, one duplication
silicone, and fresh porcine skin. A universal testing machine was used to strain
each test specimen until complete rupture and calculate its tear strength (kNm(
1)). Failure analysis was then conducted using a stereoscopic zoom light
microscope, as well as a scanning electron microscope (SEM). A shore A-type
durometer was used to measure the hardness of all specimens. RESULTS: The tear
strength for the silicones ranged from 1.75 to 9.58 kNm(-1) and the pigskin from
3.65 to 56.40 kNm(-1). The mean shore hardness for the silicones ranged from
16.275 to 62.65DU and the pigskin had a mean shore hardness of 22.65DU, with p
values <0.0125 (0.05/4). Failure analysis of the silicone materials showed the
origin of failure being in the tension side of the specimens and typical failure
patterns were observed. Examining the materials under a SEM revealed that
materials with higher viscosity presented with a larger amount of filler particle
content than silicones with low viscosity, with the duplication silicone having
no filler content. CONCLUSION: Dental silicones are a good alternative for skin
in studies that require a skin simulant.
PMID- 26434653
TI - A fatal case of electrocution with unique forensic radiological postmortem
findings.
AB - PURPOSE: Documentation of forensic radiological observations in postmortem
imaging of electrical injuries is not common yet and is less prevalent compared
to other forms of burn injuries. However, electrical injuries have high morbidity
and mortality. The objective of this case report was the visualization and
evaluation of unique electrocution-related injuries by postmortem contrast and
non-contrast enhanced imaging compared to a forensic autopsy. METHODS: Forensic
imaging included whole-body postmortem computed tomography (PMCT), PMCT
angiography (PMCTA), postmortem magnetic resonance tomography (PMMR), and PMMR
angiography (PMMRA). Initial external inspection and subsequent autopsy were
performed. RESULTS: Imaging results revealed intestinal mucosal pathologies,
particularly of the gastric vascular integrity and remarkable rhabdomyolysis of
the striated muscles of the extremities. Furthermore, PMCT and PMCTA revealed a
hepatic lesion with perihepatic free fluid. The results from external inspection
and autopsy correlated to the well-known pathologies of electrocution in the
course of a high-voltage incident. CONCLUSION: Postmortem imaging visualized
electrocution-related injuries and aided substantially in the medico-legal
investigation. These findings, particularly of the rhabdomyolysis in magnetic
resonance tomography, may support the future image interpretation of cases with
electrical injuries-in the living and the deceased.
PMID- 26434655
TI - Ultimate concerns in late modernity: Archer, Bourdieu and reflexivity.
AB - Through a critique of Margaret Archer's theory of reflexivity, this paper
explores the theoretical contribution of a Bourdieusian sociology of the subject
for understanding social change. Archer's theory of reflexivity holds that
conscious 'internal conversations' are the motor of society, central both to
human subjectivity and to the 'reflexive imperative' of late modernity. This is
established through critiques of Bourdieu, who is held to erase creativity and
meaningful personal investments from subjectivity, and late modernity is depicted
as a time when a 'situational logic of opportunity' renders embodied dispositions
and the reproduction of symbolic advantages obsolete. Maintaining Archer's focus
on 'ultimate concerns' in a context of social change, this paper argues that her
theory of reflexivity is established through a narrow misreading and rejection of
Bourdieu's work, which ultimately creates problems for her own approach. Archer's
rejection of any pre-reflexive dimensions to subjectivity and social action
leaves her unable to sociologically explain the genesis of 'ultimate concerns',
and creates an empirically dubious narrative of the consequences of social
change. Through a focus on Archer's concept of 'fractured reflexivity', the paper
explores the theoretical necessity of habitus and illusio for understanding the
social changes that Archer is grappling with. In late modernity, reflexivity is
valorized just as the conditions for its successful operation are increasingly
foreclosed, creating 'fractured reflexivity' emblematic of the complex
contemporary interaction between habitus, illusio, and accelerating social
change.
PMID- 26434654
TI - Validation of adequate endogenous reference genes for reverse transcription-qPCR
studies in human post-mortem brain tissue of SIDS cases.
AB - Sudden infant death syndrome (SIDS) is the main cause of post-neonatal infant
death in most developed countries. It is still of ambiguous etiology. Gene
expression studies of relevant target genes using reverse transcription
quantitative real-time PCR (RT-qPCR) in SIDS cases, and comparing them with age
matched controls, could help in understanding the pathogenesis of SIDS. However,
selecting inadequate reference genes used for normalization of the RT-qPCR gene
expression data can give misleading results. The aim of the present study was to
identify reference genes with the most stable expression in post-mortem brainstem
samples of SIDS and control cases. Among the five candidate reference genes
(GAPDH, GUSB, HMBS, SDHA, UBXN6) studied in both groups, SDHA and UBXN6 were
identified as the most stable. To further demonstrate the importance of using
validated genes for RT-qPCR data normalization, the expression of a potential
gene of interest in SIDS, the RPS27A gene, was evaluated using validated versus
non-validated reference genes for normalization. This gene encodes the ubiquitin
protein that has been shown in other pathological studies to be induced in SIDS.
Using the identified most stable genes for normalization of RPS27A gene
expression data revealed, as expected, a statistically significant up-regulation
in SIDS as compared to the controls. However, using a single unstable reference
gene for normalization resulted in no significant differences in transcript
abundance of RPS27A between SIDS and the controls. This emphasizes the need for
validation of the suitability of reference genes used in a given tissue type
under certain experimental conditions.
PMID- 26434656
TI - Silica Nanowires Templated by Amyloid-like Fibrils.
AB - Many peptides self-assemble to form amyloid fibrils. We previously explored the
sequence propensity to form amyloid using variants of a designed peptide with
sequence KFFEAAAKKFFE. These variant peptides form highly stable amyloid fibrils
with varied lateral assembly and are ideal to template further assembly of non
proteinaceous material. Herein, we show that the fibrils formed by peptide
variants can be coated with a layer of silica to produce silica nanowires using
tetraethyl-orthosilicate. The resulting nanowires were characterized using
electron microscopy (TEM), X-ray fiber diffraction, FTIR and cross-section EM to
reveal a nanostructure with peptidic core. Lysine residues play a role in
templating the formation of silica on the fibril surface and, using this library
of peptides, we have explored the contributions of lysine as well as arginine to
silica templating, and find that sequence plays an important role in determining
the physical nature and structure of the resulting nanowires.
PMID- 26434657
TI - Dermoscopic observation of acquired digital fibrokeratoma developed on the dorsum
of the fourth left toe.
PMID- 26434658
TI - Left Ventricular Hypertrophy Phenotype in Childhood-Onset Essential Hypertension.
AB - The aim of this study was to determine the risk factors associated with left
ventricular (LV) hypertrophy (LVH) among 89 untreated children with primary
hypertension. Clinic hypertension was confirmed by 24-hour ambulatory blood
pressure (BP) monitoring. LV mass (LVM) index was calculated as LVM (g)/height
(m)(2.7) and LVH was defined as LVM index >95th percentile. Children with (n=32)
and without (n=57) LVH were compared. Both obesity and systolic BP were
independently associated with LVH, with a higher contribution by body mass index.
Obesity contributed significantly, with a nearly nine-fold increased risk of LVH.
There was evidence of effect modification by the presence or absence of obesity
on the relationship between systolic BP and LVH, whereby the relationship existed
mainly in nonobese rather than obese children. Hence, to achieve reversal of LVH,
clinicians should take into account both BP control and weight management.
PMID- 26434660
TI - Zebrafish epiboly: Spreading thin over the yolk.
AB - Tissue thinning and spreading, a morphogenetic movement termed epiboly, is used
widely during animal development. In zebrafish, epiboly is a prominent cell
movement during gastrulation, whereby a squamous epithelium (the enveloping
layer), a multi-layer of loosely packed cells (the deep cells), and a yolk
nuclear syncytium (the yolk syncytial layer) undergo coordinated expansion to
engulf the yolk and close the blastopore. Elucidating the mechanisms that
underlie epiboly is important not only for understanding animal development in
general, but also for providing insights into fundamental cell behaviors
including cell intercalation, cell adhesion, cell signaling, and epithelial
morphogenesis. Here, recent work is reviewed with a focus on findings that
advance our understanding of (1) the role of actomyosin motors in the yolk cell
to drive epiboly, (2) the mechanisms that underlie the spreading of the
epithelial enveloping layer, and (3) the regulation of deep cell movements by E
cadherin based adhesion. A discussion of how these new insights add to the
current view of epiboly and future prospects is also presented. Overall, the
study of zebrafish epiboly can provide general and broadly applicable insights
into the genetic, molecular, and cellular control of morphogenesis.
PMID- 26434659
TI - Characterization of Mycobacterium smegmatis sigF mutant and its regulon:
overexpression of SigF antagonist (MSMEG_1803) in M. smegmatis mimics sigF mutant
phenotype, loss of pigmentation, and sensitivity to oxidative stress.
AB - In Mycobacterium smegmatis, sigF is widely expressed during different growth
stages and plays role in adaptation to stationary phase and oxidative stress.
Using a sigF deletion mutant of M. smegmatis mc(2) 155, we demonstrate that SigF
is not essential for growth of bacterium. Deletion of sigF results in loss of
carotenoid pigmentation which rendered increased susceptibility to H2 O2 induced
oxidative stress in M. smegmatis. SigF modulates the cell surface architecture
and lipid biosynthesis extending the repertoire of SigF function in this species.
M. smegmatis SigF regulon included variety of genes expressed during exponential
and stationary phases of growth and those responsible for oxidative stress, lipid
biosynthesis, energy, and central intermediary metabolism. Furthermore, we report
the identification of a SigF antagonist, an anti-sigma factor (RsbW), which upon
overexpression in M. smegmatis wild type strain produced a phenotype similar to
M. smegmatis mc(2) 155 DeltasigF strain. The SigF-anti-SigF interaction is duly
validated using bacterial two-hybrid and pull down assays. In addition, anti
sigma factor antagonists, RsfA and RsfB were identified and their interactions
with anti-sigma factor were experimentally validated. Identification of these
proteins will help decode regulatory circuit of this alternate sigma factor.
PMID- 26434661
TI - Semi-automatic outlining of levator hiatus.
AB - OBJECTIVE: To create a semi-automated outlining tool for the levator hiatus, to
reduce interobserver variability and and speed up analysis. METHODS: The proposed
automated hiatus segmentation (AHS) algorithm takes a C-plane image, in the plane
of minimal hiatal dimensions, and manually defined vertical hiatal limits as
input. The AHS then creates an initial outline by fitting predefined templates on
an intensity-invariant edge map, which is further refined using the B-spline
explicit active surfaces framework. The AHS was tested using 91 representative C
plane images. Reference hiatal outlines were obtained manually and compared with
the AHS outlines by three independent observers. The mean absolute distance
(MAD), Hausdorff distance and Dice and Jaccard coefficients were used to quantify
segmentation accuracy. Each of these metrics was calculated both for computer
observer differences (COD) and for interobserver differences. The Williams index
was used to test the null hypothesis that the automated method would agree with
the operators at least as well as the operators agreed with each other. Agreement
between the two methods was assessed using the intraclass correlation coefficient
(ICC) and Bland-Altman plots. RESULTS: The AHS contours matched well with the
manual ones (median COD, 2.10 (interquartile range (IQR), 1.54) mm for MAD). The
Williams index was greater than or close to 1 for all quality metrics, indicating
that the algorithm performed at least as well as did the manual references in
terms of interrater variability. The interobserver differences using each of the
metrics were significantly lower, and a higher ICC was achieved (0.93), when
obtaining outlines using the AHS compared with manually. The Bland-Altman plots
showed negligible bias between the two methods. Using the AHS took a median time
of 7.07 (IQR, 3.49) s, while manual outlining took 21.31 (IQR, 5.43) s, thus
being almost three-fold faster. Using the AHS, in general, the hiatus could be
outlined completely using only three points, two for initialization and one for
manual adjustment. CONCLUSIONS: We present a method for tracing the levator
hiatal outline with minimal user input. The AHS is fast, robust and reliable and
improves interrater agreement. Copyright (c) 2015 ISUOG. Published by John Wiley
& Sons Ltd.
PMID- 26434662
TI - Thiamethoxam induces oxidative stress and antioxidant response in zebrafish
(Danio Rerio) livers.
AB - Thiamethoxam, a second-generation neonicotinoid insecticide, was found to be
toxic to nontarget aquatic organisms. The purpose of this study was to
investigate the toxicity of thiamethoxam (0.30, 1.25, and 5.00 mg/L) on zebrafish
(Danio rerio) livers at the 7th, 14th, 21st, and 28th days. The reactive oxygen
species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione-s
transferase (GST), malondialdehyde (MDA) content, and DNA damage were used to
evaluate the toxic effects of thiamethoxam on zebrafish. Compared to control
groups, ROS levels were ascended in the exposure period; SOD and CAT activities
were dramatically increased during early exposure and then inhibited. GST
activity only increased on days 28. MDA content was slightly elevated on days 21
and 28. Additionally, a clear dose-response relationship was found for DNA
damage. In conclusion, thiamethoxam could induce oxidative stress and DNA damage
on the exposed zebrafish. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31:
2006-2015, 2016.
PMID- 26434663
TI - Cytogenetic and oxidative status of human lymphocytes after exposure to
clinically relevant concentrations of antimalarial drugs atovaquone and proguanil
hydrochloride in vitro.
AB - Atovaquone (ATO) and proguanil hydrochloride (PROG) is the fixed combination for
the prevention and treatment of Plasmodium falciparum malaria. As safe and
effective antimalarial drugs are needed in both the treatment and the prophylaxis
of malaria, this study was performed to investigate their possible cyto/genotoxic
potential towards human lymphocytes and the possible mechanism responsible for
it. Two different concentrations of ATO and PROG were used with and without S9
metabolic activation. The concentrations used were those found in human plasma
when a fixed-dose combination of ATO and PROG was used: 2950/130 ng/mL after
prophylactic treatment and 11 800/520 ng/mL after treatment of malaria,
respectively. Possible cellular and DNA-damaging effects were evaluated by cell
viability and alkaline comet assays, while oxidative stress potential was
evaluated by formamidopyrimidine-DNA glycosylase (Fpg)-modified comet assay, in
addition to measuring malondialdehyde and glutathione levels. According to our
results, the ATO/PROG combination displayed only weak cyto/genotoxic potential
towards human lymphocytes with no impact on oxidative stress parameters,
suggesting that oxidative stress is not implicated in their mechanism of action
towards human lymphocytes. Given that the key portion of the damaging effects was
induced after S9 metabolic activation, it is to presume that the principal
metabolite of PROG, cycloguanil, had the greatest impact. The obtained results
indicate that the ATO/PROG combination is relatively safe for the consumption
from the aspect of cyto/genotoxicity, especially if used for prophylactic
treatment. Nevertheless, further cytogenetic research and regular patient
monitoring are needed to minimize the risk of adverse events especially among
frequent travellers.
PMID- 26434664
TI - Prioritisation of citizen-centric information for disaster response.
AB - In the aftermath of a disaster event, and in the absence of trained
professionals, many responsibilities are assumed by uninjured citizens who are
willing and able to help, such as care of the injured or search and rescue. These
citizens are constrained by communications and logistics problems but are less
equipped to deal with them as most often they are cut off from any coordinated
assistance. The method proposed in this study would increase the survivability of
those injured or trapped by a disaster event by providing a facility to allow
citizens to coordinate and share information among themselves. This is
facilitated by the proposed deployment and the autonomous management of an ad hoc
infrastructure that liaises directly with survivors without central control.
Furthermore, as energy concerns present critical constraints to these networks,
this research proposes a system of categorising information elements within the
network to ensure efficient information exchange.
PMID- 26434665
TI - Evaluation of immunogenicity of LY2963016 insulin glargine compared with
Lantus(r) insulin glargine in patients with type 1 or type 2 diabetes mellitus.
AB - AIMS: To compare the immunogenicity profiles and the potential effects on
clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus(r) insulin
glargine (IGlar), products with identical primary amino acid sequences, in
patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). METHODS: To
assess immunogenicity, anti-insulin glargine antibodies (measured as percent
binding) were compared between treatments in 52-week (open-label) and 24-week
(double-blind) randomized studies in total study populations of patients with
T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients
with T2DM: insulin-naive patients and those reporting prestudy IGlar treatment
(prior IGlar). Relationships between insulin antibody levels and clinical
outcomes were assessed using analysis of covariance and partial correlations.
Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment
comparisons for treatment-emergent antibody response (TEAR) and incidence of
detectable antibodies were analysed using Fisher's exact test. RESULTS: No
significant treatment differences were observed for insulin antibody levels,
incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR
[overall and endpoint, by last-observation-carried-forward (LOCF)] in patients
with T1DM or patients with T2DM, including the insulin-naive subgroup. A
statistically significant difference was noted in the overall incidence of
detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar
subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both
treatment groups. Insulin antibody levels or developing TEAR was not associated
with clinical outcomes. CONCLUSIONS: LY IGlar and IGlar have similar
immunogenicity profiles; anti-insulin glargine antibody levels were low for both
treatments, with no observed effect on efficacy and safety outcomes.
PMID- 26434666
TI - Proteomic responses of human intestinal Caco-2 cells exposed to silver
nanoparticles and ionic silver.
AB - Even although quite a number of studies have been performed so far to demonstrate
nanoparticle-specific effects of substances in living systems, clear evidence of
these effects is still under debate. The present study was designed as a
comparative proteomic analysis of human intestinal cells exposed to a commercial
silver nanoparticle reference material and ions from AgNO3. A two-dimensional gel
electrophoresis/MALDI mass spectrometry (MS)-based proteomic analysis was
conducted after 24-h incubation of differentiated Caco-2 cells with non-cytotoxic
and low cytotoxic silver concentrations (2.5 and 25 ug ml(-1) nanosilver, 0.5 and
5 ug ml(-1) AgNO3). Out of an overall number of 316 protein spots differentially
expressed at a fold change of >= 1.4 or <= -1.4 in all treatments, 169 proteins
could be identified. In total, 231 spots were specifically deregulated in
particle-treated groups compared with 41 spots, which were limited to AgNO3
treatments. Forty-four spots (14 %) were commonly deregulated by both types of
treatment. A considerable fraction of the proteins differentially expressed after
treatment with nanoparticles is related to protein folding, synthesis or
modification of proteins as well as cellular assembly and organization. Overlays
of networks obtained for particulate and ionic treatments showed matches,
indicating common mechanisms of combined particle and ionic silver exposure and
exclusive ionic silver treatment. However, proteomic responses of Caco-2 cells
treated with higher concentrations of silver species also showed some
differences, for example regarding proteins related to fatty acid and energy
metabolism, suggesting an induction of also some different molecular mechanisms
for particle exposure and ionic treatment.
PMID- 26434667
TI - Porcine circovirus type 2 detection in in vitro produced porcine blastocysts
after virus sperm exposure.
AB - This study was aimed at assessing the capability of semen experimentally infected
with porcine circovirus type 2 (PCV2) to produce porcine blastocysts PCR positive
for PCV2. Embryos were obtained from in vitro maturation (IVM) and in vitro
fertilization (IVF) of porcine oocytes or by parthenogenesis. Sperm suspension
was exposed to PCV2b and utilized for IVF. PCV2 spiked semen did not reveal any
reduction in sperm viability or motility but its ability to produce infected
blastocysts was irrelevant as only one out of 15 blastocysts obtained by IVF were
PCV2b; however two blastocysts were PCV2a positive. Furthermore, the presence of
PCV2 was demonstrated also in embryos obtained by parthenogenesis (one out of 17
was PCV2b and one PCV2a positive). Even if PCV2 firmly attaches to the surface of
spermatozoa, experimentally spiked sperm were not effective in infecting oocytes
during IVF and in producing PCR positive embryos. The infected blastocysts we
obtained derived most probably from infected oocytes recovered at the abattoir.
PMID- 26434668
TI - Zoledronic acid suppresses callus remodeling but enhances callus strength in an
osteoporotic rat model of fracture healing.
AB - MINI-ABSTRACT: In this study, we demonstrated that the use of zoledronic acid
does not impair fracture healing, but results in superior callus size and
resistance at the fracture site, which could be the consequence of a lower rate
of bone turnover due to its anti-catabolic effect. OBJECTIVE: To investigate the
effect of inhibition of bone remodeling by the bisphosphonate, zoledronic acid,
on callus properties in an osteoporotic rat model of fracture healing. METHODS:
Ovariectomized (OVX) rats were randomly divided into four treatment groups (n=24
per group): saline control (CNT); and three systemic zoledronic acid-injected
groups (0.1mg/kg), administered 1 day (ZOLD1), 1 week (ZOLW1), and 2 weeks
(ZOLW2) after fracture. Rats were killed at either 6 or 12 weeks postoperatively.
Postmortem analyses included radiography, microcomputed tomography, histology,
histomorphometry, biomechanical tests, and nanoindentation tests. RESULTS:
Treatment with zoledronic acid led to a significant increase in trabecular bone
volume within the callus, as well as in callus resistance, compared to those in
the saline control rats; delayed administration (ZOLW2) reduced intrinsic
material properties, including ultimate stress and elastic modulus, and
microarchitecture parameters, including bone volume/total volume (BV/TV),
trabecular thickness (Tb.Th), and connectivity density (Conn.D), compared with
ZOLD1 at 12 weeks after surgery. OVX had a negative effect on the progression of
endochondral ossification at 6 weeks. Zoledronic acid administration at an early
stage following fracture may bind to early callus, and thus not affect subsequent
callus formation and endochondral ossification, while delayed administration
(ZOLW2) mildly suppresses bony callus remodeling. CONCLUSION: The superior
results obtained with zoledronic acid (ZOLD1, ZOLW1, and ZOLW2) compared to CNT
in terms of callus size and resistance could be the consequence of a lower rate
of bone turnover at the fracture site due to the anti-catabolic effect of
zoledronic acid. Mild suppression of callus remodeling by delayed administration
did not impair the initial phase of the fracture healing process.
PMID- 26434669
TI - Retrospective comparison of laparoscopic versus open radical hysterectomy after
neoadjuvant chemotherapy for locally advanced cervical cancer.
AB - OBJECTIVE: To compare outcomes after laparoscopic radical hysterectomy (LRH) and
abdominal radical hysterectomy (ARH) for locally advanced cervical cancer
(LACC)after neoadjuvant chemotherapy (NACT). METHODS: In a retrospective study,
data were analyzed from patients with FIGO stage IB2-IIB cervical cancer who
underwent LRH or ARH after NACT at Union Hospital, Wuhan, China, between January
2007 and August 2013.Perioperative outcomes and survival were compared. RESULTS:
Overall, 99 patients who underwent LRH and 30 who underwent ARH were included.
Compared with ARH patients, LRH patients presented with lower-stage tumors
(P=0.013). Median operative time, number of harvested lymph nodes, and rate of
positive surgical margins did not differ significantly between the groups, but
LRH resulted in less blood loss (median 300mL [range 20-1100] vs 375mL [100
1200]; P=0.027). There were two intraoperative complications and 23 postoperative
complications in the LRH group, and 12 postoperative complications in the ARH
group. No conversions occurred in the LRH group; all complications were managed
without severe sequelae. As of March 2014, recurrence had been noted for 6(6.1%)
LRH patients and 2 (6.7%) ARH patients. CONCLUSION: LRH was similar to ARH in
terms of safety, feasibility, and morbidity, with less blood loss among women
with LACC undergoing NACT. Long-term outcomes need to be documented.
PMID- 26434670
TI - Organization and evaluation of a pilot cervical cancer screening program in
Morocco.
AB - OBJECTIVE: To evaluate a pilot program for early detection of cervical cancer
using visual inspection with acetic acid (VIA) and the loop electrosurgical
excision procedure (LEEP) in one region of Morocco. METHODS: A descriptive
analysis of the screening outcome measures of 43 participating primary care units
and one reference center for LEEP was conducted in Meknes-Tafilalet between
January 1, 2011, and December 31, 2013. Data on the number of participants, VIA
results, colposcopy, and treatment were used in analyses. RESULTS: Of the 308 197
women in the target age group (30-49 years), 18 586 (6.0%) were screened by VIA.
Positive screening test results were recorded for 1628 (8.8%) women, of whom 1144
(70.3%) received diagnostic confirmation by colposcopy. Of the 87 (7.6%) women
with cervical intraepithelial neoplasia, only 16 (18.4%) underwent LEEP; three
cases of invasive cervical cancer were diagnosed. CONCLUSION: Issues with
implementation of the screening program were found, including low compliance and
a low treatment rate of cervical intraepithelial neoplasia by LEEP. By contrast,
high rates of colposcopy referral were observed. Screen-and-treat by ablative
methods (e.g. thermocoagulation) should be considered to increase treatment rates
at national scale-up.
PMID- 26434671
TI - Socio-structural and behavioral risk factors associated with trafficked history
of female bar/spa entertainers in the sex trade in the Philippines.
AB - OBJECTIVE: To explore factors associated with trafficking (deceptive/coercive
entry to sex trade) among female bar/spa entertainers who traded sex in the
Philippines. METHOD: Female bar/spa entertainers who traded sex in the past
6months were recruited from 25bar/spa venues in Metro Manila (April 2009-January
2010) and assessed via cross-sectional survey data collection for HIV-risk
related socio-structural factors associated with deceptive/coercive entry into
the sex trade. The study employed hierarchical linear modeling. RESULTS: Of
166bar/spa entertainers assessed, 19 (11.4%) reported being deceived/coerced
(i.e. trafficked) into their first jobs. Trafficking history was independently
associated with current drug use (adjusted odds ratio [AOR] 2.05; 95% confidence
interval [CI] 1.00-3.97) decreased availability of condoms at venues for
entertainers (AOR 0.18; 95% CI 0.05-0.71) and, conversely, increased peer support
for practicing safer sex behaviors (AOR 3.08; 95% CI 1.63-5.09). Those
deceived/coerced into their positions were more likely than non-trafficked women
to have been recruited by an agency who came to their rural province (AOR 12.07;
95% CI 1.77-82.25) as opposed to getting the job from advertisement (AOR 0.10;
95% CI 0.02-0.65) or a friend/acquaintance (AOR 0.02; 95% CI 0.00-0.48).
CONCLUSION: The findings have implications for designing interventions to prevent
and target trafficked women in the Philippines who may be more vulnerable to
substance use and, potentially, HIV infection.
PMID- 26434672
TI - Emil Kraepelin's concepts of the phenomenology and physiology of sleep: The first
systematic description of chronotypes.
AB - Emil Kraepelin is considered one of the most influential psychiatrists ever. His
research on sleep, however, has received little attention to date. Therefore,
Kraepelin's published work was reviewed, statements on the topic "sleep"
identified, historically contextualized and compared with current knowledge. His
assumptions on the "physiology of sleep" are rather speculative and not
substantiated by own research. The opposite is true for his findings on the
"phenomenology of sleep". For example, his results on sleep depth and sleep
stages are not only in overall good agreement with current concepts, but also
based on sleep studies. Of special relevance are his findings on chronotypes:
Based on empirical clinical studies, neuropsychological experiments and sleep
studies, Kraepelin systematically described a morning and evening disposition and
intermediate types on the basis of the maximum physical capacity, cognitive
ability and alertness/sleepiness during the day as well as sleeping habits. In
fact, this concept is basically still valid and these aspects are being captured
in morningness-eveningness scales. Our findings challenge the common notion that
Nathaniel Kleitman was the first to systematically describe the morningness
eveningness dimension. Overall, we deem Kraepelin's contributions to sleep
research, compiled here for the first time, well worth being acknowledged by
modern sleep research.
PMID- 26434673
TI - A systematic review and meta-analysis of randomized controlled trials of
cognitive behavior therapy for insomnia (CBT-I) in cancer survivors.
AB - This review examined the efficacy of cognitive behavior therapy for insomnia (CBT
I) in people diagnosed with cancer. Studies were identified through November 2014
using multiple databases, clinical trial records, and bibliography searches.
Inclusion was limited to randomized controlled trials of CBT-I conducted in
individuals with a cancer diagnosis who had clinically relevant insomnia. The
primary outcome variable was sleep efficiency (SE) as measured by sleep diary.
Eight studies including data from 752 cancer survivors met inclusion criteria.
CBT-I resulted in a 15.5% improvement in SE relative to control conditions (6.1%)
from pre- to post-intervention, with a medium effect size (ES: d = 0.53).
Overall, sleep latency was reduced by 22 min with an ES of d = 0.43, compared to
a reduction of 8 min in the control conditions. Wake after sleep onset was
reduced by 30 min with an ES of d = 0.41, compared to 13 min in the control
conditions. Large effect sizes were observed for self-reported insomnia severity
(d = 0.77) for those patients who received CBT-I, representing a clinically
relevant eight point reduction. Effects were durable up to 6 mo. The quality of
the evidence supports a strong recommendation for the use of CBT-I among cancer
survivors.
PMID- 26434674
TI - The etiology of delayed sleep phase disorder.
AB - According to classification manuals for sleep disorders, nine disorders are
directly related to biological clock timing misalignments. Of all, delayed sleep
phase disorder (DSPD) is the most commonly diagnosed, predominantly affecting
adolescents, young adults, and insomnia patients. It is a persistent inability to
fall asleep at earlier, more desirable and socially conventional times, coupled
with extreme difficulty awakening in the morning. Considerable evidence shows a
delay in the circadian clock to be associated with DSPD. Therefore, treatments
have mainly focused on advancing the biological clock and sleep timing through
pharmacotherapy, phototherapy and behavioral therapies. The clinical evidence
indicates that these treatments are efficacious, at least in the short term.
However, follow up studies show frequent patient relapse, leading researchers to
speculate that alternative etiologies may be contributing to sleep and circadian
clock delays in DSPD. The aim of the present paper is to review and collate
current literature related to DSPD etiology in order to outline gaps in current
knowledge and suggest future research.
PMID- 26434678
TI - Phonon transport control by nanoarchitecture including epitaxial Ge nanodots for
Si-based thermoelectric materials.
AB - Phonon transport in Si films was controlled using epitaxially-grown ultrasmall Ge
nanodots (NDs) with ultrahigh density for the purpose of developing Si-based
thermoelectric materials. The Si/Ge ND stacked structures, which were formed by
the ultrathin SiO2 film technique, exhibited lower thermal conductivities than
those of the conventional nanostructured SiGe bulk alloys, despite the stacked
structures having a smaller Ge fraction. This came from the large thermal
resistance caused by phonon scattering at the Si/Ge ND interfaces. The phonon
scattering can be controlled by the Ge ND structure, which was independent of Si
layer structure for carrier transport. These results demonstrate the
effectiveness of ultrasmall epitaxial Ge NDs as phonon scattering sources,
opening up a route for the realisation of Si-based thermoelectric materials.
PMID- 26434679
TI - Control of a chemical reaction (photodegradation of the p3ht polymer) with
nonlocal dielectric environments.
AB - Proximity to metallic surfaces, plasmonic structures, cavities and other
inhomogeneous dielectric environments is known to control spontaneous emission,
energy transfer, scattering, and many other phenomena of practical importance.
The aim of the present study was to demonstrate that, in spirit of the Marcus
theory, the rates of chemical reactions can, too, be influenced by nonlocal
dielectric environments, such as metallic films and metal/dielectric bilayer or
multilayer structures. We have experimentally shown that metallic, composite
metal/dielectric substrates can, indeed, control ordering as well as
photodegradation of thin poly-3-hexylthiophene (p3ht) films. In many particular
experiments, p3ht films were separated from metal by a dielectric spacer,
excluding conventional catalysis facilitated by metals and making modification of
the nonlocal dielectric environment a plausible explanation for the observed
phenomena. This first step toward understanding of a complex relationship between
chemical reactions and nonlocal dielectric environments is to be followed by the
theory development and a broader scope of thorough experimental studies.
PMID- 26434680
TI - The importance of spatial heterogeneity and self-restraint on mutualism stability
- a quantitative review.
AB - Understanding the factors that enable mutualisms to evolve and to subsequently
remain stable over time, is essential to fully understand patterns of global
biodiversity and for evidence based conservation policy. Theoretically, spatial
heterogeneity of mutualists, through increased likelihood of fidelity between
cooperative partners in structured populations, and 'self-restraint' of
symbionts, due to selection against high levels of virulence leading to short
term host overexploitation, will result in either a positive correlation between
the reproductive success of both mutualists prior to the total exploitation of
any host resource or no correlation after any host resource has been fully
exploited. A quantitative review by meta-analysis on the results of 96 studies
from 35 papers, showed no evidence of a significant fitness correlation between
mutualists across a range of systems that captured much taxonomic diversity.
However, when the data were split according to four categories of host: 1)
cnidarian corals, 2) woody plants, 3) herbaceous plants, and 4) insects, a
significantly positive effect in corals was revealed. The trends for the
remaining three categories did not significantly differ to zero. Our results
suggest that stability in mutualisms requires alternative processes, or
mechanisms in addition to, spatial heterogeneity of hosts and/or 'self-restraint'
of symbionts.
PMID- 26434681
TI - Azobenzene Modified Imidacloprid Derivatives as Photoswitchable Insecticides:
Steering Molecular Activity in a Controllable Manner.
AB - Incorporating the photoisomerizable azobenzene into imidacloprid produced a
photoswitchable insecticidal molecule as the first neonicotinoid example of
remote control insecticide performance with spatiotemporal resolution. The
designed photoswitchable insecticides showed distinguishable activity against
Musca both in vivo and in vitro upon irradiation. Molecular docking study further
suggested the binding difference of the two photoisomers. The generation of these
photomediated insecticides provides novel insight into the insecticidal activity
facilitating further investigation on the functions of insect nicotinic
acetylcholine receptors and opens a novel way to control and study insect
behavior on insecticide poisoning using light.
PMID- 26434684
TI - Blood-brain barrier disruption during spontaneous canine visceral leishmaniasis.
AB - Visceral leishmaniasis is a complex disease caused by Leishmania infantum, and in
dogs, besides the classical symptoms, there are descriptions of inflammatory
alterations in the brain. Brain inflammation is a strictly controlled process,
and as the brain counts on the efficiency of the blood-brain barrier (BBB), we
aimed to assess BBB integrity in dogs with spontaneous visceral leishmaniasis.
Therefore, we evaluated markers in the cerebrospinal fluid (CSF) and in brain
tissue related to BBB disruption and brain inflammation. Elevated albumin quota
revealed BBB breakdown, corroborated by increased concentrations of anti
Leishmania antibodies in the CSF. In the brain, albumin and IgG staining formed
halos around blood vessels, a classical indicator of BBB leakage. Soluble IgG was
also detected in the choroid plexus and ependyma, and in these structures, IgG
stained random resident cells. IgG(+) cells and Fcgamma-RI(+) cells were
identified in the choroid plexus, ependyma and perivascular in the brain
parenchyma. The data support the occurrence of BBB disruption in dogs with
spontaneous visceral leishmaniasis, and IgG as a key molecule that is capable of
initiating and/or maintaining the inflammatory stimuli in the nervous milieu and
the CSF as an important disseminator of inflammatory stimuli within the CNS.
PMID- 26434682
TI - Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery
aneurysm formation in Kawasaki disease in Han Chinese in Taiwan.
AB - Kawasaki disease (KD) is an acute, inflammatory, and self-limited vasculitis
affecting infants and young children. Coronary artery aneurysm (CAA) formation is
the major complication of KD and the leading cause of acquired cardiovascular
disease among children. To identify susceptible loci that might predispose
patients with KD to CAA formation, a genome-wide association screen was performed
in a Taiwanese KD cohort. Patients with both KD and CAA had longer fever duration
and delayed intravenous immunoglobulin treatment time. After adjusting for these
factors, 100 susceptibility loci were identified. Four genes were identified from
a single cluster of 35 using the Ingenuity Pathway Analysis (IPA) Knowledge Base.
Silencing KCNQ5, PLCB1, PLCB4, and PLCL1 inhibited the effect of
lipopolysaccharide-induced endothelial cell inflammation with varying degrees of
proinflammatory cytokine expression. PLCB1 showed the most significant
inhibition. Endothelial cell inflammation was also inhibited by using a
phospholipase C (PLC) inhibitor. The single nucleotide polymorphism rs6140791 was
identified between PLCB4 and PLCB1. Plasma PLC levels were higher in patients
with KD and CC+CG rs6140791genotypes, and these genotypes were more prevalent in
patients with KD who also had CAA. Our results suggest that polymorphism of the
PLCB4/B1 genes might be involved in the CAA pathogenesis of KD.
PMID- 26434683
TI - Prenatal ethanol exposure increases osteoarthritis susceptibility in female rat
offspring by programming a low-functioning IGF-1 signaling pathway.
AB - Epidemiological evidence indicates that osteoarthritis (OA) and prenatal ethanol
exposure (PEE) are both associated with low birth weight but possible causal
interrelationships have not been investigated. To investigate the effects of PEE
on the susceptibility to OA in adult rats that experienced intrauterine growth
retardation (IUGR), and to explore potential intrauterine mechanisms, we
established the rat model of IUGR by PEE and dexamethasone, and the female fetus
and 24-week-old adult offspring subjected to strenuous running for 6 weeks were
sacrificed. Knee joints were collected from fetuses and adult offspring for
histochemistry, immunohistochemistry and qPCR assays. Histological analyses and
the Mankin score revealed increased cartilage destruction and accelerated OA
progression in adult offspring from the PEE group compared to the control group.
Immunohistochemistry showed reduced expression of insulin-like growth factor-1
(IGF-1) signaling pathway components. Furthermore, fetuses in the PEE group
experienced IUGR but exhibited a higher postnatal growth rate. The expression of
many IGF-1 signaling components was downregulated, which coincided with reduced
amounts of type II collagen in the epiphyseal cartilage of fetuses in the PEE
group. These results suggest that PEE enhances the susceptibility to OA in female
adult rat offspring by down-regulating IGF-1 signaling and retarding articular
cartilage development.
PMID- 26434685
TI - Total lesion glycolysis by 18F-FDG PET/CT is independent prognostic factor in
patients with advanced non-small cell lung cancer.
AB - BACKGROUND AND AIMS: To determine whether the primary tumor SUVmax and total
lesion glycolysis (TLG) measured on 18 F-FDG PET/CT have prognostic significance
in patients with non-small-cell lung cancer (NSCLC). METHODS: A retrospective
review identified 142 patients NSCLC who underwent 18 F-FDG PET/CT at the time of
diagnosis. The affect of the SUVmax and TLG of the primary tumor on survival were
examined. RESULTS: Total 142 patients were included the study. Thirty-two
patients were at early stage (stage I and II) and 110 patients were at advanced
stage (stage III and IV). Both early and advanced stage patients were divided
into two groups according to SUVmax 12 as low and high SUVmax groups. Overall
survival (OS) of the low SUVmax group was significantly longer than higher SUVmax
group for early-stage patients (35.8 +/- 15.3 vs 21.8 +/- 13.3, P = 0.013). But
there was no differences in advanced stage patients for OS (16.1 +/- 14.8 vs 17.0
+/- 15.1, P = 0.862). Primary lesion TLG of the 99 patients were calculated. For
advanced stage, the patients with the lower TLG had significantly longer survival
time (P < 0.001). In multivariate analysis only TLG remained significant
predictor of OS in advanced stage patients (HR and 95% confidence interval =
7.716 and 1.664-4.342, respectively). CONCLUSION: High SUVmax is related to poor
OS in patients with surgically resected early stage (stage I and II) NSCLC, but
it is not an independent prognostic factor. TLG is a prognostic measurement and
it is independent predictor factor of survival for advanced stage NSCLC.
PMID- 26434687
TI - Visible-Light Photoreduction of CO2 in a Metal-Organic Framework: Boosting
Electron-Hole Separation via Electron Trap States.
AB - It is highly desirable to convert CO2 to valuable fuels or chemicals by means of
solar energy, which requires CO2 enrichment around photocatalysts from the
atmosphere. Here we demonstrate that a porphyrin-involved metal-organic framework
(MOF), PCN-222, can selectively capture and further photoreduce CO2 with high
efficiency under visible-light irradiation. Mechanistic information gleaned from
ultrafast transient absorption spectroscopy (combined with time-resolved
photoluminescence spectroscopy) has elucidated the relationship between the
photocatalytic activity and the electron-hole separation efficiency. The presence
of a deep electron trap state in PCN-222 effectively inhibits the detrimental,
radiative electron-hole recombination. As a direct result, PCN-222 significantly
enhances photocatalytic conversion of CO2 into formate anion compared to the
corresponding porphyrin ligand itself. This work provides important insights into
the design of MOF-based materials for CO2 capture and photoreduction.
PMID- 26434686
TI - Effectiveness of Polyvalent Bacterial Lysate and Autovaccines Against Upper
Respiratory Tract Bacterial Colonization by Potential Pathogens: A Randomized
Study.
AB - BACKGROUND: Polyvalent bacterial lysate (PBL) is an oral immunostimulating
vaccine consisting of bacterial standardized lysates obtained by lysis of
different strains of bacteria. Autovaccines are individually prepared based on
the results of smears obtained from the patient. Both types of vaccine can be
used to treat an ongoing chronic infection. This study sought to determine which
method is more effective against nasal colonization by potential respiratory
tract pathogens. MATERIAL AND METHODS: We enrolled 150 patients with aerobic Gram
stain culture and count results indicating bacterial colonization of the nose
and/or throat by potential pathogens. The participants were randomly assigned to
each of the following groups: 1. administration of PBL, 2. administration of
autovaccine, and 3. no intervention (controls). RESULTS: Reduction of the
bacterial count in Streptococcus pneumoniae-colonized participants was
significant after the autovaccine (p<0.001) and PBL (p<0.01). Reduction of the
bacterial count of other beta-hemolytic streptococcal strains after treatment
with the autovaccine was significant (p<0.01) and was non-significant after PBL.
In Haemophilus influenzae colonization, significant reduction in the bacterial
count was noted in the PBL group (p<0.01). Methicillin-resistant Staphylococcus
aureus colonization did not respond to either treatment. CONCLUSIONS: The
autovaccine is more effective than PBL for reducing bacterial count of
Streptococcus pneumoniae and beta-hemolytic streptococci, while PBL was more
effective against Haemophilus influenzae colonization.
PMID- 26434688
TI - CMAP decrement as a potential diagnostic marker for ALS.
AB - OBJECTIVE: We previously reported that decrement of compound muscle action
potential (CMAP) by repetitive nerve stimulation (RNS) was greater in the median
nerves than in the ulnar nerves of patients with amyotrophic lateral sclerosis
(ALS). The aim of this study was to evaluate whether CMAP decrement by RNS is a
feasible marker for the differentiation of ALS from other diseases. MATERIALS &
METHODS: We performed RNS in the median and ulnar nerves of 51 patients with ALS
and 40 patients with other diseases. RESULTS: The CMAP decrement was
significantly greater in the median nerves of patients with ALS, compared to the
disease control patients. In the median nerves of patients with ALS, CMAP
decrement was significantly greater in the cervical region-onset group than in
the other region-onset group. CONCLUSIONS: The finding of CMAP decrement in the
median nerves can be useful for differentiating ALS patients with cervical region
onset from other controls with active neuropathic diseases.
PMID- 26434689
TI - Thermal Degradation of Small Molecules: A Global Metabolomic Investigation.
AB - Thermal processes are widely used in small molecule chemical analysis and
metabolomics for derivatization, vaporization, chromatography, and ionization,
especially in gas chromatography mass spectrometry (GC/MS). In this study the
effect of heating was examined on a set of 64 small molecule standards and,
separately, on human plasma metabolite extracts. The samples, either derivatized
or underivatized, were heated at three different temperatures (60, 100, and 250
degrees C) at different exposure times (30 s, 60 s, and 300 s). All the samples
were analyzed by liquid chromatography coupled to electrospray ionization mass
spectrometry (LC/MS) and the data processed by XCMS Online (
xcmsonline.scripps.edu ). The results showed that heating at an elevated
temperature of 100 degrees C had an appreciable effect on both the underivatized
and derivatized molecules, and heating at 250 degrees C created substantial
changes in the profile. For example, over 40% of the molecular peaks were altered
in the plasma metabolite analysis after heating (250 degrees C, 300s) with a
significant formation of degradation and transformation products. The analysis of
64 small molecule standards validated the temperature-induced changes observed on
the plasma metabolites, where most of the small molecules degraded at elevated
temperatures even after minimal exposure times (30 s). For example, tri- and
diorganophosphates (e.g., adenosine triphosphate and adenosine diphosphate) were
readily degraded into a mono-organophosphate (e.g., adenosine monophosphate)
during heating. Nucleosides and nucleotides (e.g., inosine and inosine
monophosphate) were also found to be transformed into purine derivatives (e.g.,
hypoxanthine). A newly formed transformation product, oleoyl ethyl amide, was
identified in both the underivatized and derivatized forms of the plasma extracts
and small molecule standard mixture, and was likely generated from oleic acid.
Overall these analyses show that small molecules and metabolites undergo
significant time-sensitive alterations when exposed to elevated temperatures,
especially those conditions that mimic sample preparation and analysis in GC/MS
experiments.
PMID- 26434690
TI - Knowledge, attitude, and practices with respect to disease surveillance among
urban private practitioners in Pune, India.
AB - BACKGROUND: Participation of private practitioners in routine disease
surveillance in India is minimal despite the fact that they account for over 70%
of the primary healthcare provision. We aimed to investigate the knowledge,
attitudes, and practices of private practitioners in the city of Pune toward
disease surveillance. Our goal was to identify what barriers and facilitators
determine their participation in current and future surveillance efforts. DESIGN:
A questionnaire-based survey was conducted among 258 practitioners (response rate
86%). Data were processed using SPSSTM Inc., Chicago, IL, USA, version 17.0.1.
RESULTS: Knowledge regarding surveillance, although limited, was better among
allopathy practitioners. Surveillance practices did not differ significantly
between allopathy and alternate medicine practitioners. Multivariable logistic
regression suggested practicing allopathy [odds ratio (OR) 3.125, 95% confidence
interval (CI) 1.234-7.915, p=0.016] and availability of a computer (OR 3.670, 95%
CI 1.237-10.889, p=0.019) as significant determinants and the presence of a
laboratory (OR 3.792, 95% CI 0.998-14.557, p=0.052) as a marginal determinant of
the practitioner's willingness to participate in routine disease surveillance
systems. Lack of time (137, 55%) was identified as the main barrier at the
individual level alongside inadequately trained subordinate staff (14, 6%). Main
extrinsic barriers included lack of cooperation between government and the
private sector (27, 11%) and legal issues involved in reporting data (15, 6%).
There was a general agreement among respondents (239, 94%) that current
surveillance efforts need strengthening. Over a third suggested that availability
of detailed information and training about surveillance processes (70, 33%) would
facilitate reporting. CONCLUSIONS: The high response rate and the practitioners'
willingness to participate in a proposed pilot non-communicable disease
surveillance system indicate that there is a general interest from the private
sector in cooperating. Keeping reporting systems simple, preferably in electronic
formats that minimize infrastructure and time requirements on behalf of the
private practitioners, will go a long way in consolidating disease surveillance
efforts in the state. Organizing training sessions, providing timely feedback,
and awarding continuing medical education points for routine data reporting seem
feasible options and should be piloted.
PMID- 26434691
TI - 'You must carry your wheelchair'--barriers to accessing healthcare in a South
African rural area.
AB - BACKGROUND: There is international evidence that people with disabilities face
barriers when accessing primary healthcare services and that there is inadequate
information about effective interventions that work to improve the lives of
people with disabilities, especially in low-income and middle-income countries.
Poor rural residents generally experience barriers to accessing primary
healthcare, and these problems are further exacerbated for people with
disabilities. OBJECTIVE: In this study, we explore the challenges faced by people
with disabilities in accessing healthcare in Madwaleni, a poor rural Xhosa
community in South Africa. DESIGN: Purposive sampling was done with 26
participants, using semi-structured interviews and content analysis to identify
major themes. RESULTS: This study showed a number of barriers to healthcare for
people with disabilities. These included practical barriers, including
geographical and staffing issues, and attitudinal barriers. CONCLUSIONS: It is
suggested that although there are practical barriers that need to be addressed,
attitudinal barriers could potentially be addressed more easily and cost
effectively.
PMID- 26434692
TI - A Colorimetric Plasmonic Nanosensor for Dosimetry of Therapeutic Levels of
Ionizing Radiation.
AB - Modern radiation therapy using highly automated linear accelerators is a complex
process that maximizes doses to tumors and minimizes incident dose to normal
tissues. Dosimeters can help determine the radiation dose delivered to target
diseased tissue while minimizing damage to surrounding healthy tissue. However,
existing dosimeters can be complex to fabricate, expensive, and cumbersome to
operate. Here, we demonstrate studies of a liquid phase, visually evaluated
plasmonic nanosensor that detects radiation doses commonly employed in
fractionated radiotherapy (1-10 Gy) for tumor ablation. We accomplished this by
employing ionizing radiation, in concert with templating lipid surfactant
micelles, in order to convert colorless salt solutions of univalent gold ions
(Au(1)) to maroon-colored dispersions of plasmonic gold nanoparticles.
Differences in color intensities of nanoparticle dispersions were employed as
quantitative indicators of the radiation dose. The nanoparticles thus formed were
characterized using UV-vis absorbance spectroscopy, dynamic light scattering, and
transmission electron microscopy. The role of lipid surfactants on nanoparticle
formation was investigated by varying the chain lengths while maintaining the
same headgroup and counterion; the effect of surfactant concentration on
detection efficacy was also investigated. The plasmonic nanosensor was able to
detect doses as low as 0.5 Gy and demonstrated a linear detection range of 0.5-2
Gy or 5-37 Gy depending on the concentration of the lipid surfactant employed.
The plasmonic nanosensor was also able to detect radiation levels in
anthropomorphic prostate phantoms when administered together with endorectal
balloons, indicating its potential utility as a dosimeter in fractionated
radiotherapy for prostate cancer. Taken together, our results indicate that this
simple visible nanosensor has strong potential to be used as a dosimeter for
validating delivered radiation doses in fractionated radiotherapies in a variety
of clinical settings.
PMID- 26434693
TI - Contrasting the Role of Mg and Ba Doping on the Microstructure and Thermoelectric
Properties of p-Type AgSbSe2.
AB - Microstructure has a critical influence on the mechanical and functional
properties. For thermoelectric materials, deep understanding of the relationship
of microstructure and thermoelectric properties will enable the rational
optimization of the ZT value and efficiency. Herein, taking AgSbSe2 as an
example, we first report a different role of alkaline-earth metal ions (Mg(2+)
and Ba(2+)) doping in the microstructure and thermoelectric properties of p-type
AgSbSe2. For Mg doping, it monotonously increases the carrier concentration and
then reduces the electrical resistivity, leading to a substantially enhanced
power factor in comparison to those of other dopant elements (Bi(3+), Pb(2+),
Zn(2+), Na(+), and Cd(2+)) in the AgSbSe2 system. Meanwhile, the lattice thermal
conductivity is gradually suppressed by point defects scattering. In contrast,
the electrical resistivity first decreases and then slightly rises with the
increased Ba-doping concentrations due to the presence of BaSe3 nanoprecipitates,
exhibiting a different variation tendency compared with the corresponding Mg
doped samples. More significantly, the total thermal conductivity is obviously
reduced with the increased Ba-doping concentrations partially because of the
strong scattering of medium and long wavelength phonons via the nanoprecipitates,
consistent with the theoretical calculation and analysis. Collectively, ZT value
~1 at 673 K and calculated leg efficiency ~8.5% with Tc = 300 K and Th = 673 K
are obtained for both AgSb0.98Mg0.02Se2 and AgSb0.98Ba0.02Se2 samples.
PMID- 26434694
TI - Selective Access to Heterocyclic Sulfonamides and Sulfonyl Fluorides via a
Parallel Medicinal Chemistry Enabled Method.
AB - A sulfur-functionalized aminoacrolein derivative is used for the efficient and
selective synthesis of heterocyclic sulfonyl chlorides, sulfonyl fluorides, and
sulfonamides. The development of a 3-step parallel medicinal chemistry (PMC)
protocol for the synthesis of pyrazole-4-sulfonamides effectively demonstrates
the utility of this reagent. This reactivity was expanded to provide rapid access
to other heterocyclic sulfonyl fluorides, including pyrimidines and pyridines,
whose corresponding sulfonyl chlorides lack suitable chemical stability.
PMID- 26434695
TI - Probing Anisotropic Surface Properties of Molybdenite by Direct Force
Measurements.
AB - Probing anisotropic surface properties of layer-type mineral is fundamentally
important in understanding its surface charge and wettability for a variety of
applications. In this study, the surface properties of the face and the edge
surfaces of natural molybdenite (MoS2) were investigated by direct surface force
measurements using atomic force microscope (AFM). The interaction forces between
the AFM tip (Si3N4) and face or edge surface of molybdenite were measured in 10
mM NaCl solutions at various pHs. The force profiles were well-fitted with
classical DLVO (Derjaguin-Landau-Verwey-Overbeek) theory to determine the surface
potentials of the face and the edge surfaces of molybdenite. The surface
potentials of both the face and edge surfaces become more negative with
increasing pH. At neutral and alkaline conditions, the edge surface exhibits more
negative surface potential than the face surface, which is possibly due to
molybdate and hydromolybdate ions on the edge surface. The point of zero charge
(PZC) of the edge surface was determined around pH 3 while PZC of the face
surface was not observed in the range of pH 3-11. The interaction forces between
octadecyltrichlorosilane-treated AFM tip (OTS-tip) and face or edge surface of
molybdenite were also measured at various pHs to study the wettability of
molybdenite surfaces. An attractive force between the OTS-tip and the face
surface was detected. The force profiles were well-fitted by considering DLVO
forces and additional hydrophobic force. Our results suggest the hydrophobic
feature of the face surface of molybdenite. In contrast, no attractive force
between the OTS-tip and the edge surface was detected. This is the first study in
directly measuring surface charge and wettability of the pristine face and edge
surfaces of molybdenite through surface force measurements.
PMID- 26434696
TI - Surgical Procedure Characteristics and Risk of Sharps-Related Blood and Body
Fluid Exposure.
AB - OBJECTIVE To use a unique multicomponent administrative data set assembled at a
large academic teaching hospital to examine the risk of percutaneous blood and
body fluid (BBF) exposures occurring in operating rooms. DESIGN A 10-year
retrospective cohort design. SETTING A single large academic teaching hospital.
PARTICIPANTS All surgical procedures (n=333,073) performed in 2001-2010 as well
as 2,113 reported BBF exposures were analyzed. METHODS Crude exposure rates were
calculated; Poisson regression was used to analyze risk factors and account for
procedure duration. BBF exposures involving suture needles were examined
separately from those involving other device types to examine possible
differences in risk factors. RESULTS The overall rate of reported BBF exposures
was 6.3 per 1,000 surgical procedures (2.9 per 1,000 surgical hours). BBF
exposure rates increased with estimated patient blood loss (17.7 exposures per
1,000 procedures with 501-1,000 cc blood loss and 26.4 exposures per 1,000
procedures with >1,000 cc blood loss), number of personnel working in the
surgical field during the procedure (34.4 exposures per 1,000 procedures having
>=15 personnel ever in the field), and procedure duration (14.3 exposures per
1,000 procedures lasting 4 to <6 hours, 27.1 exposures per 1,000 procedures
lasting >=6 hours). Regression results showed associations were generally
stronger for suture needle-related exposures. CONCLUSIONS Results largely support
other studies found in the literature. However, additional research should
investigate differences in risk factors for BBF exposures associated with suture
needles and those associated with all other device types. Infect. Control Hosp.
Epidemiol. 2015;37(1):80-87.
PMID- 26434697
TI - Destabilization of the torsioned conformation of a ligand side chain inverts the
LXRbeta activity.
AB - BACKGROUND: Liver X receptors (LXRs) are transcription factors activated by
cholesterol metabolites containing an oxidized side chain. Due to their ability
to regulate lipid metabolism and cholesterol transport, they have become
attractive pharmacological targets. LXRs are closely related to DAF-12, a nuclear
receptor involved in nematode lifespan and regulated by the binding of C-27
steroidal acids. Based on our recent finding that the lack of the C-25 methyl
group does not abolish their DAF-12 activity, we evaluated the effect of removing
it from the (25R)-cholestenoic acid, a LXR agonist. METHODS: The binding mode and
the molecular basis of action of 27-nor-5-cholestenoic acid were evaluated using
molecular dynamics simulations. The biological activity was investigated using
reporter gene expression assays and determining the expression levels of
endogenous target genes. The in vitro MARCoNI assay was used to analyze the
interaction with cofactors. RESULTS: 27-Nor-5-cholestenoic acid behaves as an
inverse agonist. This correlates with the capacity of the complex to better bind
corepressors rather than coactivators. The C-25 methyl moiety would be necessary
for the maintenance of a torsioned conformation of the steroid side chain that
stabilizes an active LXRbeta state. CONCLUSION: We found that a 27-nor analog is
able to act as a LXR ligand. Interestingly, this minimal structural change on the
steroid triggered a drastic change in the LXR response. GENERAL SIGNIFICANCE:
Results contribute to improve our understanding on the molecular basis of LXRbeta
mechanisms of action and provide a new scaffold in the quest for selective LXR
modulators.
PMID- 26434698
TI - Experimental evidence of heparanase, Hsp70 and NF-kappaB gene expression on the
response of anti-inflammatory drugs in TNBS-induced colonic inflammation.
AB - AIM: Etiopathogenesis of inflammatory bowel disease is unclear and results from a
complex interplay of genetic, microbial, environmental and immune factors.
Elucidating the mechanisms that drive IBD depends on the detailed
characterization of human inflammatory mediators in animal models. Therefore, we
studied how intestinal inflammation affects heparanase, NF-kappaB and Hsp70 gene
expression in rats, and if current intestinal anti-inflammatory drugs
(sulphasalazine, prednisolone and azathioprine) act on these expressions.
Moreover, we investigated the relationships among these genes with colonic
cytokines levels (IL-1beta, TNF-alpha, IL-6, INF-gamma and IL-10) and oxidative
stress that have fundamental role in IBD. MATERIAL AND METHODS: Macroscopic
parameters (diarrhea, extension of lesion, colonic weight/length ratio and damage
score), biochemical markers (myeloperoxidase and alkaline phosphatase activities,
and glutathione, IL-1beta, TNF-alpha, IL-6, INF-gamma and IL-10 levels), gene
expressions (heparanase, NF-kappaB and Hsp70), and microscopic evaluations
(optic, electronic scanning and transmission microscopic) were performed in rats.
KEY FINDINGS: Expression of heparanase, Hsp70 and NF-kappaB and oxidative stress
were increased by inflammatory process and differentially modulated by
sulphasalazine, prednisolone and azathioprine treatments. Protective effects of
drugs were also related to differential modulation of cytokine changes induced by
inflammatory process, showing different mechanisms to control inflammation.
SIGNIFICANCE: Heparanase, NF-kappaB and Hsp70 gene expression participate in the
inflammatory response induced by TNBS and represent pharmacological targets of
the intestinal anti-inflammatory drugs. In addition, current drugs used to treat
IBD (sulphasalazine, prednisolone and azathioprine) differentially modulate
heparanase, NF-kappaB and Hsp70 gene expression, cytokine production and
oxidative stress.
PMID- 26434699
TI - Linoleic acid and breast cancer risk: a meta-analysis.
AB - OBJECTIVE: Prior studies on linoleic acid, the predominant n-6 fatty acid, and
breast cancer risk have generated inconsistent results. We performed a meta
analysis to summarize the evidence regarding the relationship of dietary and
serum linoleic acid with breast cancer risk. DESIGN: Pertinent studies were
identified by a search of PubMed and EMBASE. The fixed- or random-effect pooled
measure was selected based on between-study heterogeneity. RESULTS: Eight
prospective cohort studies and four prospective nested case-control studies,
involving 10 410 breast cancer events from 358 955 adult females across different
countries, were included in present study. Compared with the lowest level of
linoleic acid, the pooled relative risk (RR; 95 % CI) of breast cancer was 0.98
(0.93, 1.04) for the highest level of linoleic acid. The pooled RR (95 % CI) for
dietary and serum linoleic acid were 0.99 (0.92, 1.06) and 0.98 (0.88, 1.08),
respectively. The RR (95 % CI) of breast cancer was 0.97 (0.91, 1.04), 0.95
(0.85, 1.07), 0.96 (0.86, 1.07), 0.98 (0.87, 1.10) and 0.99 (0.85, 1.14) for
linoleic acid intake of 5, 10, 15, 20 and 25 g/d, respectively. The risk of
breast cancer decreased by 1 % (RR=0.99; 95 % CI 0.93, 1.05) for every 10 g/d
increment in linoleic acid intake. CONCLUSIONS: This meta-analysis indicated that
both dietary linoleic acid intake and serum linoleic acid level were associated
with decreased risk of breast cancer, although none of the associations were
statistically significant. Further investigations are warranted.
PMID- 26434701
TI - The real root-cause analysis: Optimizing surgical options in the current era.
PMID- 26434700
TI - 7-prenyloxi-6-methoxycoumarin from Polygala sabulosa A.W. Bennett Regulates p38
MAPK and NF-kB Pathways Inhibiting the Inflammation Induced by Carrageenan in the
Mouse Model of Pleurisy.
AB - CONTEXT: Polygala sabulosa, popularly known as "timutu-pinheirinho," has been
used in Brazilian folk medicine for the treatment of bowel and kidney disorders
and as an expectorant. OBJECTIVE: Evaluate the anti-inflammatory effects of the
crude extract (CE), acetonic fraction (Ac), and the main compound, 7-prenyloxi-6
methoxycoumarin (PC) on a mouse model of carrageenan-induced pleurisy. MATERIALS
AND METHODS: A mouse model of carrageenan-induced pleurisy was used to
investigate the effects of P. sabulosa CE, Ac and PC on leukocyte migration,
exudate formation, activities of myeloperoxidase (MPO), and adenosine-deaminase
(ADA), levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL
1beta) and nitric oxide (NO). In addition, the effect of the plant material on
lung histology was also evaluated. The effects of PC on the TNF-alpha, IL-1beta
and NO synthase 2 (NOS2) mRNA expression, were also investigated. Finally, the
effect of PC on the nuclear factor-kappa B (NF-kappaB) and p38 mitogen-activated
protein kinase (p38 MAPK) was also evaluated. RESULTS: CE, Ac and PC reduced
inflammation in the pleural cavity and lungs. This effect was evidenced by
reduction on all inflammatory parameters evaluated; the exception being the
inability of the CE to inhibit exudate formation. In isolation, PC showed
reduction on mRNA levels of TNF-alpha, IL-1beta and NOS2, and on activation of
the NF-kappaB and p38 MAPK pathways. CONCLUSION: The presented results show that
P. sabulosa has significant anti-inflammatory activity, as does its main
compound, PC. Moreover, the results suggest that PC exerts its effects mainly by
inhibited the NF-kappaB and p38 MAPK pathways.
PMID- 26434702
TI - Bleeding and cerebral injury following aortic arch repair: Two chinks in the
armor.
PMID- 26434703
TI - Gibbons of the world, dream on.
PMID- 26434704
TI - A reliability assessment of constrained spherical deconvolution-based diffusion
weighted magnetic resonance imaging in individuals with chronic stroke.
AB - BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) is commonly
used to assess white matter properties after stroke. Novel work is utilizing
constrained spherical deconvolution (CSD) to estimate complex intra-voxel fiber
architecture unaccounted for with tensor-based fiber tractography. However, the
reliability of CSD-based tractography has not been established in people with
chronic stroke. NEW METHOD: Establishing the reliability of CSD-based DW-MRI in
chronic stroke. High-resolution DW-MRI was performed in ten adults with chronic
stroke during two separate sessions. Deterministic region of interest-based fiber
tractography using CSD was performed by two raters. Mean fractional anisotropy
(FA), apparent diffusion coefficient (ADC), tract number, and tract volume were
extracted from reconstructed fiber pathways in the corticospinal tract (CST) and
superior longitudinal fasciculus (SLF). Callosal fiber pathways connecting the
primary motor cortices were also evaluated. Inter-rater and test-retest
reliability were determined by intra-class correlation coefficients (ICCs).
RESULTS: ICCs revealed excellent reliability for FA and ADC in ipsilesional (0.86
1.00; p<0.05) and contralesional hemispheres (0.94-1.00; p<0.0001), for CST and
SLF fibers; and excellent reliability for all metrics in callosal fibers (0.85
1.00; p<0.05). ICC ranged from poor to excellent for tract number and tract
volume in ipsilesional (-0.11 to 0.92; p<=0.57) and contralesional hemispheres (
0.27 to 0.93; p<=0.64), for CST and SLF fibers. COMPARISON WITH EXISTING METHOD:
Like other select DW-MRI approaches, CSD-based tractography is a reliable
approach to evaluate FA and ADC in major white matter pathways, in chronic
stroke. CONCLUSION: Future work should address the reproducibility and utility of
CSD-based metrics of tract number and tract volume.
PMID- 26434705
TI - Models of hypoxia and ischemia-induced seizures.
AB - Despite greater understanding and improved management, seizures continue to be a
major problem in childhood. Neonatal seizures are often refractory to
conventional antiepileptic drugs, and can result in later life epilepsy and
cognitive deficits, conditions for which there are no specific treatments.
Hypoxic and/or ischemic encephalopathy (HIE) is the most common cause for
neonatal seizures, and accounts for more than two-thirds of neonatal seizure
cases. A better understanding of the cellular and molecular mechanisms is
essential for identifying new therapeutic strategies that control the neonatal
seizures and its cognitive consequences. This heavily relies on animal models
that play a critical role in discovering novel mechanisms underlying both
epileptogenesis and associated cognitive impairments. To date, a number of animal
models have provided a tremendous amount of information regarding the
pathophysiology of HIE-induced neonatal seizures. This review provides an
overview on the most important features of the main animal models of HIE-induced
seizures. In particular, we focus on the methodology of seizure induction and the
characterizations of post-HIE injury consequences. These aspects of HIE-induced
seizure models are discussed in the light of the suitability of these models in
studying human HIE-induced seizures.
PMID- 26434706
TI - Human brain slices for epilepsy research: Pitfalls, solutions and future
challenges.
AB - Increasingly, neuroscientists are taking the opportunity to use live human tissue
obtained from elective neurosurgical procedures for electrophysiological studies
in vitro. Access to this valuable resource permits unique studies into the
network dynamics that contribute to the generation of pathological electrical
activity in the human epileptic brain. Whilst this approach has provided insights
into the mechanistic features of electrophysiological patterns associated with
human epilepsy, it is not without technical and methodological challenges. This
review outlines the main difficulties associated with working with epileptic
human brain slices from the point of collection, through the stages of
preparation, storage and recording. Moreover, it outlines the limitations, in
terms of the nature of epileptic activity that can be observed in such tissue, in
particular, the rarity of spontaneous ictal discharges, we discuss manipulations
that can be utilised to induce such activity. In addition to discussing
conventional electrophysiological techniques that are routinely employed in
epileptic human brain slices, we review how imaging and multielectrode array
recordings could provide novel insights into the network dynamics of human
epileptogenesis. Acute studies in human brain slices are ultimately limited by
the lifetime of the tissue so overcoming this issue provides increased
opportunity for information gain. We review the literature with respect to
organotypic culture techniques that may hold the key to prolonging the viability
of this material. A combination of long-term culture techniques, viral
transduction approaches and electrophysiology in human brain slices promotes the
possibility of large scale monitoring and manipulation of neuronal activity in
epileptic microcircuits.
PMID- 26434707
TI - Spatially Structured Sparse Morphological Component Separation for voltage
sensitive dye optical imaging.
AB - BACKGROUND: Voltage-sensitive dye optical imaging is a promising technique for
studying in vivo neural assemblies dynamics where functional clustering can be
visualized in the imaging plane. Its practical potential is however limited by
many artifacts. NEW METHOD: We present a novel method, that we call "SMCS"
(Spatially Structured Sparse Morphological Component Separation), to separate the
relevant biological signal from noise and artifacts. It extends Generalized
Linear Models (GLM) by using a set of convex non-smooth regularization priors
adapted to the morphology of the sources and artifacts to capture. RESULTS: We
make use of first order proximal splitting algorithms to solve the corresponding
large scale optimization problem. We also propose an automatic parameters
selection procedure based on statistical risk estimation methods. COMPARISON WITH
EXISTING METHODS: We compare this method with blank subtraction and GLM methods
on both synthetic and real data. It shows encouraging perspectives for the
observation of complex cortical dynamics. CONCLUSIONS: This work shows how recent
advances in source separation can be integrated into a biophysical model of
VSDOI. Going beyond GLM methods is important to capture transient cortical events
such as propagating waves.
PMID- 26434708
TI - Energy production through organic fraction of municipal solid waste-A multiple
regression modeling approach.
AB - In the 21st century, people migrated from rural to urban areas for several
reasons. As a result, the populations of Indian cities are increasing day by day.
On one hand, the country is developing in the field of science and technology and
on the other hand, it is encountering a serious problem called 'Environmental
degradation'. Due to increase in population, the generation of solid waste is
also increased and is being disposed in open dumps and landfills which lead to
air and land pollution. This study is attempted to generate energy out of organic
solid waste by the bio- fermentation process. The study was conducted for a
period of 7 months at Erode, Tamilnadu and the reading on various parameters like
Hydraulic retention time, organic loading rate, sludge loading rate, influent pH,
effluent pH, inlet volatile acids, out let volatile fatty acids, inlet VSS/TS
ratio, outlet VSS/TS ratio, influent COD, effluent COD and % of COD removal are
recorded for every 10 days. The aim of the present study is to develop a model
through multiple linear regression analysis with COD as dependent variable and
various parameters like HRT, OLR, SLR, influent, effluent, VSS/TS ratio, influent
COD, effluent COD, etc as independent variables and to analyze the impact of
these parameters on COD. The results of the model developed through step-wise
regression method revealed that only four parameters Influent COD, effluent COD,
VSS/TS and Influent/pH were main influencers of COD removal. The parameters
influent COD and VSS/TS have positive impact on COD removal and the parameters
effluent COD and Influent/pH have negative impact. The parameter Influent COD has
the highest order of impact, followed by effluent COD, VSS/TS and influent pH.
The other parameters HRT, OLR, SLR, INLET VFA and OUTLET VFA were not
significantly contributing to the removal of COD. The implementation of the
process suggested through this study might bring in dual benefit to the
community, viz treatment of solid waste and creation of energy.
PMID- 26434709
TI - The spinal antinociceptive mechanism determined by systemic administration of
BD1047 in zymosan-induced hyperalgesia in rats.
AB - Although sigma-1 receptor (Sig-1R) antagonists have a potential antinociceptive
effect in inflammatory diseases, the precise mechanism is not fully understood.
The present study was aimed to elucidate the role of spinal neurons and microglia
in the anti-nociceptive mechanism of BD1047 (a prototypical Sig-1R antagonist)
using an inflammatory pain model based on intraplantar injection of zymosan. Oral
pretreatment with BD1047 dose-dependently reduced zymosan-induced thermal and
mechanical hyperalgesia as well as spinal neuronal activation including increased
immunoreactivity of Fos, protein kinase C (PKC) and 'PKC-dependent
phosphorylation of the NMDA receptor subunit 1' (pNR1). Zymosan also led to
increased CD11b immunoreactivity (a marker of microglia) accompanied by
'phosphorylated p38 mitogen activated protein kinase' (p-p38MAPK) and interleukin
1betaimmunoreactivity in the spinal dorsal horn. Intrathecal injection of a
microglia modulator (minocycline), p38MAPK inhibitor (SB203580) or interleukin
1betaneutralizing antibody significantly attenuated zymosan-induced hyperalgesia.
Specifically, oral pretreatment with BD1047 reduced the immunoreactivity of
CD11b, p-p38MAPK and interleukin-1beta. In the spinal cord section, Sig-1R
immunoreactivity was exclusively distributed in both spinal dorsal horn neurons
and central endings of unmyelinated primary afferent fibers but not in glia.
Intrathecal injection of BD1047 alleviated zymosan-induced hyperalgesia up to the
level of oral administration. Taken together, our data imply that antinociceptive
effect induced by oral treatment with BD1047 may be mediated, at least in part,
by the inhibition of neuronal and microglial activation in the spinal cord
triggered by inflammatory conditions.
PMID- 26434710
TI - Developmental toxicity studies with 6 forms of titanium dioxide test materials (3
pigment-different grade & 3 nanoscale) demonstrate an absence of effects in
orally-exposed rats.
AB - Six different commercial forms and sizes of titanium dioxide particles were
tested in separate developmental toxicity assays. The three pigment-grade (pg) or
3 ultrafine (uf)/nanoscale (anatase and/or rutile) titanium dioxide (TiO2)
particle-types were evaluated for potential maternal and developmental toxicity
in pregnant rats by two different laboratories. All studies were conducted
according to OECD Guideline 414 (Prenatal Developmental Toxicity Study). In
addition, all test materials were robustly characterized. The BET surface areas
of the pg and uf samples ranged from 7 to 17 m(2)/g and 50-82 m(2)/g respectively
(see Table 1). The test substances were formulated in sterile water. In all of
the studies, the formulations were administered by oral gavage to time-mated rats
daily beginning around the time of implantation and continuing until the day
prior to expected parturition. In 3 of the studies (uf-1, uf-3, & pg-1), the
formulations were administered to Crl:CD(SD) rats beginning on gestation day (GD)
6 through GD 20. In 3 additional studies (uf-2, and pg-2, pg-3 TiO2 particles),
the formulations were administered to Wistar rats beginning on GD 5 through 19.
The dose levels used in all studies were 0, 100, 300, or 1000 mg/kg/day; control
group animals were administered the vehicle. During the in-life portions of the
studies, body weights, food consumption, and clinical observations before and
after dosing were collected on a daily basis. All dams were euthanized just prior
to expected parturition (GD 21 for Crl:CD(SD) rats and GD 20 for Wistar rats).
The gross necropsies included an examination and description of uterine contents
including counts of corpora lutea, implantation sites, resorptions, and live and
dead fetuses. All live fetuses were sexed, weighed, and examined externally and
euthanized. Following euthanasia, fresh visceral and head examinations were
performed on selected fetuses. The fetal carcasses were then processed and
examined for skeletal alterations. There was no evidence of maternal or
developmental toxicity at any dose level tested in any of the six studies. Based
on these results, the no-observed-adverse-effect level (NOAEL) for titanium
dioxide was 1000 mg/kg/day, the highest administered dose, in both the Sprague
Dawley (Crl:CD(SD) and Wistar rat strains.
PMID- 26434711
TI - A first insight into temperature stress-induced neuroendocrine and immunological
changes in giant freshwater prawn, Macrobrachium rosenbergii.
AB - Haemolymph norepinephrine (NE); total haemocyte count (THC); respiratory bursts
(RBs); superoxide dismutase (SOD), phenoloxidase (PO), and phagocytic activity;
and prophenoloxidase (proPO)-system-related genes (lipopolysaccharide- and beta
1,3-glucan-binding protein: LGBP, proPO, peroxinectin: PE, and alpha2
macroglobulin: alpha2-M) in haemocytes of Macrobrachium rosenbergii were
investigated after transferring them from 28 degrees C to 22 degrees C, 28
degrees C, and 34 degrees C respectively. The results revealed that haemolymph
NE, hyaline cells (HCs), and PO activity per granulocyte increased from 30 to 120
min of exposure, and however, RBs and phagocytic activity significantly decreased
from 30 to 120 min of exposure as well as granular cells (GCs), semigranular
cells (SGCs), and SOD activity decreased from 60 to 120 min of exposure for the
prawns subjected to temperature stress. The proPO-system-related gene expression
markedly increased with 60-120 min of exposure for the prawns transferred from 28
degrees C to 22 degrees C and 34 degrees C, except alpha2M at 120 min. These
results provide a first insight into the effects of temperature stress on
haemolymph NE level and immune functions in prawns and suggest that temperature
stress-induced acute modulation in immunity is associated with the release of
haemolymph NE in M. rosenbergii.
PMID- 26434712
TI - Occurrence of immune cells in the intestinal wall of Squalius cephalus infected
with Pomphorhynchus laevis.
AB - A sub-population of 34 specimens of chub, Squalius cephalus, was sampled from the
River Brenta (Northern Italy) and examined for ecto- and endo-parasites.
Pomphorhynchus laevis (Acanthocephala) was the only enteric helminth encountered.
Immunofluorescence and ultrastructural studies were conducted on the intestines
of chub. Near the site of parasite's attachment, mucous cells, mast cells (MCs),
neutrophils and rodlet cells (RCs) were found to co-occur within the intestinal
epithelium. The numbers of mucous cells, MCs and neutrophils were significantly
higher in infected fish (Mann-Whitney U test, p < 0.05). Dual immunofluorescence
staining with the lectin Dolichos Biflorus Agglutinin (DBA) and the macrophage
specific MAC387 monoclonal antibody, with parallel transmission electron
microscopy, revealed that epithelial MCs often made intimate contact with the
mucous cells. Degranulation of a large number of MCs around the site of the
acanthocephalan's attachment and in proximity to mucous cells was also
documented. MCs and neutrophils were abundant in the submucosa. Immune cells of
the intestinal epithelium have been described at the ultrastructural level and
their possible functions and interactions are discussed.
PMID- 26434713
TI - Uncaria tomentosa increases growth and immune activity in Oreochromis niloticus
challenged with Streptococcus agalactiae.
AB - Cat's claw (Uncaria tomentosa) is an Amazon herb using in native cultures in
Peru. In mammals, it has been described several effects of this herb. However,
this is the first report of its use on the diet of fish. The aim of this study
was to determinate the effect of this plant on the growth and immune activity in
Oreochromis niloticus. Nile tilapia (81.3 +/- 4.5 g) were distributed into 5
groups and supplemented with 0 (non-supplement fish), 75, 150, 300, and 450 mg of
U. tomentosa.kg(-1) of diet for a period of 28 days. Fish were inoculated in the
swim bladder with inactivated Streptococcus agalactiae and samples were taken at
6, 24, and 48 h post inoculation (HPI). Dose dependent increases were noted in
some of the evaluated times of thrombocytes and white blood cells counts (WBC) in
blood and exudate, burst respiratory activity, lysozyme activity,
melanomacrophage centers count (MMCs), villi length, IgM by immunohistochemistry
in splenic tissue, and unexpectedly on growth parameters. However, dietary
supplementation of this herb did not affect red blood cells count (RBC),
hemoglobin, and there were no observed histological lesions in gills, intestine,
spleen, and liver. The current results demonstrate for the first time that U.
tomentosa can stimulate fish immunity and improve growth performance in Nile
tilapia.
PMID- 26434714
TI - YHV-responsive gene expression under the influence of PmRelish regulation.
AB - In animals, infection by Gram-negative bacteria and certain viruses activates the
Imd signaling pathway wherein the a NF-kappaB transcription factor, Relish, is a
key regulatory protein for the synthesis of antimicrobial proteins. Infection by
yellow head virus (YHV) activates the Imd pathway. To investigate the expression
of genes involved in YHV infection and under the influence of PmRelish
regulation, RNA interference and suppression subtractive hybridization (SSH) are
employed. The genes in forward library expressed in shrimp after YHV infection
and under the activity of PmRelish were obtained by subtracting the cDNAs from
YHV-infected and PmRelish-knockdown shrimp with cDNAs from YHV-infected shrimp.
Opposite subtraction gave a reverse library whereby an alternative set of genes
under YHV infection and no PmRelish expression were obtained. Nucleotide
sequences of 252 and 99 cDNA clones from the forward and reverse libraries,
respectively, were obtained and annotated through blast search against the
GenBank sequences. Genes involved in defense and homeostasis were abundant in
both libraries, 31% and 23% in the forward and reverse libraries, respectively.
They were predominantly antimicrobial proteins, proteinases and proteinase
inhibitors. The expression of antimicrobial protein genes, ALFPm3, crustinPm1,
penaeidin3 and penaeidin5 were tested under PmRelish silencing and Gram-negative
bacterium Vibrio harveyi infection. Together with the results using YHV infection
previously reported, the expression of penaeidin5 and also penaeidin3 but not
ALFPm3 and crustinPm1 were under the regulation of PmRelish in the Imd pathway.
PMID- 26434715
TI - Genome-wide identification and characterization of TRAF genes in the Yesso
scallop (Patinopecten yessoensis) and their distinct expression patterns in
response to bacterial challenge.
AB - The tumor necrosis factor (TNF) receptor associated factors (TRAFs) are the major
signal transducers for the TNF receptor superfamily and the interleukin-1
receptor/Toll-like receptor (IL-1R/TLR) superfamily, which regulate a variety of
cellular activities and innate immune responses. TRAF genes have been extensively
studied in various species, including vertebrates and invertebrates. However, as
one of the key component of NF-kappaB pathway, TRAF genes have not been
systematically characterized in marine invertebrates. In this study, we
identified and characterized five TRAF genes, PyTRAF2, PyTRAF3, PyTRAF4, PyTRAF6
and PyTRAF7, in the Yesso scallop (Patinopecten yessoensis). Phylogenetic and
protein structural analyses were conducted to determine their identities and
evolutionary relationships. In comparison with the TRAF genes from vertebrate
species, the structural features were all relatively conserved in the PyTRAF
genes. To gain insights into the roles of TRAF genes during scallop innate immune
responses, quantitative real-time PCR was used to investigate the expression
profiles in the different stages of scallop development, in the healthy adult
tissues, and in the hemocytes after bacterial infection with Micrococcus luteus
and Vibrio anguillarum. Based on the qRT-PCR analysis, the expression of most of
the PyTRAFs was significantly induced in the acute phases (3-6 h) after infection
with Gram-positive (M. luteus) and Gram-negative (V. anguillarum) bacteria, and
many more dramatic changes in PyTRAFs expression were observed after V.
anguillarum challenge. Notably, the strong response in the up-regulation of
PyTRAF6 post-bacterial challenge was distinct from that previously reported in
scallops and crabs but was similar to that of other shellfish, Echinodermata and
even teleost fish. The high level expressions of PyTRAFs in the hemocytes and the
gill, and their specific expression patterns after challenges provide insights
into the versatile roles and responses of TRAFs in the innate immune system
against Gram-negative bacterial pathogens in bivalves.
PMID- 26434716
TI - Mucosal expression signatures of two Cathepsin L in channel catfish (Ictalurus
punctatus) following bacterial challenge.
AB - The mucosal surfaces of fish are the first line of host defense against various
pathogens. The mucosal immune responses are the most critical events to prevent
pathogen attachment and invasion. Cathepsins are a group of peptidases that
involved in different levels of immune responses, but the knowledge of the roles
of Cathepsin in mucosal immune responses against bacterial infection are still
lacking. Therefore, in the present study we characterized the Cathepsin L gene
family in channel catfish, and profiled their expression levels after challenging
with two different Gram-negative bacterial pathogens. Here, two Cathepsin L genes
were identified from channel catfish and were designated CTSL1a and CTSL.1.
Comparing to other fish species, the catfish CTSL genes are highly conserved in
their structural features. Phylogenetic analysis was conducted to confirm the
identification of CTSL genes. Expression analysis revealed that the CTSL genes
were ubiquitously expressed in all tested tissues. Following infection, the CTSL
genes were significantly induced at most timepoints in mucosal tissues. But the
expression patterns varied depending on both pathogen and tissue types,
suggesting that CTSL genes may exert disparate functions or exhibit distinct
tissue-selective roles in mucosal immune responses. Our findings here, clearly
revealed the key roles of CTSL in catfish mucosal immunity; however, further
studies are needed to expand functional characterization and examine whether CTSL
may also play additional physiological roles in catfish mucosal tissues.
PMID- 26434718
TI - Ganglioside GM3 as a gatekeeper of obesity-associated insulin resistance:
Evidence and mechanisms.
AB - Gangliosides constitute a large family of sialic acid-containing
glycosphingolipids which play a key regulatory role in a diverse array of
cellular processes, including receptor-associated signalling. Accordingly, the
aberrant production of the ganglioside GM3 has been linked to pathophysiological
changes associated with obesity, which in turn can lead to metabolic disorders
such as insulin resistance and type 2 diabetes mellitus. This review examines the
role of GM3 in mediating obesity-induced perturbations in metabolic function,
including impaired insulin action. By doing so, we highlight the potential use of
therapies targeting GM3 biosynthesis in order to counteract obesity-related
metabolic disorders.
PMID- 26434717
TI - High pressure promotes alpha-synuclein aggregation in cultured neuronal cells.
AB - alpha-Synuclein is found in plaques associated with Parkinson's and other
neurodegenerative diseases. Changes in alpha-synuclein oligomerization are
thought to give rise to nucleation of neurodegenerative plaques. Here, we
investigated the effect of hydrostatic pressure on the aggregation of alpha
synuclein in cultured neuronal cells. We found that hydrostatic pressure is
associated with a transition from monomeric to higher order alpha-synuclein
aggregates. We then tested whether this aggregation is associated with the loss
of binding partners, such as phospholipase Cbeta. We found that increased
pressure reduces the level of PLCbeta1 and the amount of alpha-synuclein/PLCbeta1
complexes. These studies suggest that pressure promotes release of alpha
synuclein from protein partners promoting its oligomerization.
PMID- 26434719
TI - Alternative Transposition Generates New Chimeric Genes and Segmental Duplications
at the Maize p1 Locus.
AB - The maize Ac/Ds transposon family was the first transposable element system
identified and characterized by Barbara McClintock. Ac/Ds transposons belong to
the hAT family of class II DNA transposons. We and others have shown that Ac/Ds
elements can undergo a process of alternative transposition in which the Ac/Ds
transposase acts on the termini of two separate, nearby transposons. Because
these termini are present in different elements, alternative transposition can
generate a variety of genome alterations such as inversions, duplications,
deletions, and translocations. Moreover, Ac/Ds elements transpose preferentially
into genic regions, suggesting that structural changes arising from alternative
transposition may potentially generate chimeric genes at the rearrangement
breakpoints. Here we identified and characterized 11 independent cases of gene
fusion induced by Ac alternative transposition. In each case, a functional
chimeric gene was created by fusion of two linked, paralogous genes; moreover,
each event was associated with duplication of the ~70-kb segment located between
the two paralogs. An extant gene in the maize B73 genome that contains an
internal duplication apparently generated by an alternative transposition event
was also identified. Our study demonstrates that alternative transposition
induced duplications may be a source for spontaneous creation of diverse genome
structures and novel genes in maize.
PMID- 26434720
TI - The Effects of Background and Interference Selection on Patterns of Genetic
Variation in Subdivided Populations.
AB - It is well known that most new mutations that affect fitness exert deleterious
effects and that natural populations are often composed of subpopulations (demes)
connected by gene flow. To gain a better understanding of the joint effects of
purifying selection and population structure, we focus on a scenario where an
ancestral population splits into multiple demes and study neutral diversity
patterns in regions linked to selected sites. In the background selection regime
of strong selection, we first derive analytic equations for pairwise coalescent
times and FST as a function of time after the ancestral population splits into
two demes and then construct a flexible coalescent simulator that can generate
samples under complex models such as those involving multiple demes or
nonconservative migration. We have carried out extensive forward simulations to
show that the new methods can accurately predict diversity patterns both in the
nonequilibrium phase following the split of the ancestral population and in the
equilibrium between mutation, migration, drift, and selection. In the
interference selection regime of many tightly linked selected sites, forward
simulations provide evidence that neutral diversity patterns obtained from both
the nonequilibrium and equilibrium phases may be virtually indistinguishable for
models that have identical variance in fitness, but are nonetheless different
with respect to the number of selected sites and the strength of purifying
selection. This equivalence in neutral diversity patterns suggests that data
collected from subdivided populations may have limited power for differentiating
among the selective pressures to which closely linked selected sites are subject.
PMID- 26434721
TI - Simple Biophysical Model Predicts Faster Accumulation of Hybrid Incompatibilities
in Small Populations Under Stabilizing Selection.
AB - Speciation is fundamental to the process of generating the huge diversity of life
on Earth. However, we are yet to have a clear understanding of its molecular
genetic basis. Here, we examine a computational model of reproductive isolation
that explicitly incorporates a map from genotype to phenotype based on the
biophysics of protein-DNA binding. In particular, we model the binding of a
protein transcription factor to a DNA binding site and how their independent
coevolution, in a stabilizing fitness landscape, of two allopatric lineages leads
to incompatibilities. Complementing our previous coarse-grained theoretical
results, our simulations give a new prediction for the monomorphic regime of
evolution that smaller populations should develop incompatibilities more quickly.
This arises as (1) smaller populations have a greater initial drift load, as
there are more sequences that bind poorly than well, so fewer substitutions are
needed to reach incompatible regions of phenotype space, and (2) slower
divergence when the population size is larger than the inverse of discrete
differences in fitness. Further, we find longer sequences develop
incompatibilities more quickly at small population sizes, but more slowly at
large population sizes. The biophysical model thus represents a robust mechanism
of rapid reproductive isolation for small populations and large sequences that
does not require peak shifts or positive selection. Finally, we show that the
growth of DMIs with time is quadratic for small populations, agreeing with Orr's
model, but nonpower law for large populations, with a form consistent with our
previous theoretical results.
PMID- 26434725
TI - Reaction of diazocompounds with C70: unprecedented synthesis and characterization
of isomeric [5,6]-fulleroids.
AB - The synthesis of a variety of PCBM-type [5,6]-fulleroids and their further highly
selective photoisomerization to the respective [6,6]-methanofullerenes is
presented. Interestingly, the chemical reactivity of [5,6]-fulleroids reveals the
same trend (a > b > c > d) to that observed for pristine C70 (alpha > beta >
gamma > delta).
PMID- 26434722
TI - Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure
and Caenorhabditis elegans Gastrulation.
AB - Neural tube defects including spina bifida are common and severe congenital
disorders. In mice, mutations in more than 200 genes can result in neural tube
defects. We hypothesized that this large gene set might include genes whose
homologs contribute to morphogenesis in diverse animals. To test this hypothesis,
we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a
topologically similar process to vertebrate neural tube closure. Both C. elegans
gastrulation and vertebrate neural tube closure involve the internalization of
surface cells, requiring tissue-specific gene regulation, actomyosin-driven
apical constriction, and establishment and maintenance of adhesions between
specific cells. Our screen identified several neural tube defect gene homologs
that are required for gastrulation in C. elegans, including the transcription
factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early
endodermally expressed genes as well as genes expressed in other early cell
lineages, establishing sptf-3 as a key contributor to multiple well-studied C.
elegans cell fate specification pathways. We also identified members of the actin
regulatory WAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of
WAVE complex members reduced the narrowing of endodermal cells' apical surfaces.
Although WAVE complex members are expressed broadly in C. elegans, we found that
expression of a vertebrate WAVE complex member, nckap1, is enriched in the
developing neural tube of Xenopus. We show that nckap1 contributes to neural tube
closure in Xenopus. This work identifies in vivo roles for homologs of mammalian
neural tube defect genes in two manipulable genetic model systems.
PMID- 26434723
TI - The Importance of cGMP Signaling in Sensory Cilia for Body Size Regulation in
Caenorhabditis elegans.
AB - The body size of Caenorhabditis elegans is thought to be controlled by sensory
inputs because many mutants with sensory cilium structure defects exhibit small
body size. The EGL-4 cGMP-dependent protein kinase acts in sensory neurons to
reduce body size when animals fail to perceive sensory signals. In addition to
body size control, EGL-4 regulates various other behavioral and developmental
pathways, including those involved in the regulation of egg laying and chemotaxis
behavior. Here we have identified gcy-12, which encodes a receptor-type guanylyl
cyclase, as a gene involved in the sensory regulation of body size. Analyses with
GFP fusion constructs showed that gcy-12 is expressed in several sensory neurons
and localizes to sensory cilia. Genetic analyses indicated that GCY-12 acts
upstream of EGL-4 in body size control but does not affect other EGL-4 functions.
Our studies indicate that the function of the GCY-12 guanylyl cyclase is to
provide cGMP to the EGL-4 cGMP-dependent kinase only for limited tasks including
body size regulation. We also found that the PDE-2 cyclic nucleotide
phosphodiesterase negatively regulates EGL-4 in controlling body size. Thus, the
cGMP level is precisely controlled by GCY-12 and PDE-2 to determine body size
through EGL-4, and the defects in the sensory cilium structure may disturb the
balanced control of the cGMP level. The large number of guanylyl cyclases encoded
in the C. elegans genome suggests that EGL-4 exerts pleiotropic effects by
partnering with different guanylyl cyclases for different downstream functions.
PMID- 26434724
TI - Natural Variations in SLG7 Regulate Grain Shape in Rice.
AB - Rice (Oryza sativa) grain shape, which is controlled by quantitative trait loci
(QTL), has a strong effect on yield production and quality. However, the
molecular basis for grain development remains largely unknown. In this study, we
identified a novel QTL, Slender grain on chromosome 7 (SLG7), that is responsible
for grain shape, using backcross introgression lines derived from 9311 and
Azucena. The SLG7 allele from Azucena produces longer and thinner grains,
although it has no influence on grain weight and yield production. SLG7 encodes a
protein homologous to LONGIFOLIA 1 and LONGIFOLIA 2, both of which increase organ
length in Arabidopsis. SLG7 is constitutively expressed in various tissues in
rice, and the SLG7 protein is located in plasma membrane. Morphological and
cellular analyses suggested that SLG7 produces slender grains by longitudinally
increasing cell length, while transversely decreasing cell width, which is
independent from cell division. Our findings show that the functions of SLG7
family members are conserved across monocots and dicots and that the SLG7 allele
could be applied in breeding to modify rice grain appearance.
PMID- 26434726
TI - Zinc is a transmembrane agonist that induces platelet activation in a tyrosine
phosphorylation-dependent manner.
AB - Following platelet adhesion and primary activation at sites of vascular injury,
secondary platelet activation is induced by soluble platelet agonists, such as
ADP, ATP, thrombin and thromboxane. Zinc ions are also released from platelets
and damaged cells and have been shown to act as a platelet agonist. However, the
mechanism of zinc-induced platelet activation is not well understood. Here we
show that exogenous zinc gains access to the platelet cytosol and induces full
platelet aggregation that is dependent on platelet protein tyrosine
phosphorylation, PKC and integrin alphaIIbbeta3 activity and is mediated by
granule release and secondary signalling. ZnSO4 increased the binding affinity of
GpVI, but not integrin alpha2beta1. Low concentrations of ZnSO4 potentiated
platelet aggregation by collagen-related peptide (CRP-XL), thrombin and
adrenaline. Chelation of intracellular zinc reduced platelet aggregation induced
by a number of different agonists, inhibited zinc-induced tyrosine
phosphorylation and inhibited platelet activation in whole blood under
physiologically relevant flow conditions. Our data are consistent with a
transmembrane signalling role for zinc in platelet activation during thrombus
formation.
PMID- 26434727
TI - Polyvinylpyrrolidone (PVP) in nanoparticle synthesis.
AB - Colloidal synthesis offers a route to nanoparticles (NPs) with controlled
composition and structural features. This Perspective describes the use of
polyvinylpyrrolidone (PVP) to obtain such nanostructures. PVP can serve as a
surface stabilizer, growth modifier, nanoparticle dispersant, and reducing agent.
As shown with examples, its role depends on the synthetic conditions. This
dependence arises from the amphiphilic nature of PVP along with the molecular
weight of the selected PVP. These characteristics can affect nanoparticle growth
and morphology by providing solubility in diverse solvents, selective surface
stabilization, and even access to kinetically controlled growth conditions. This
Perspective includes discussions of the properties of PVP-capped NPs for surface
enhanced Raman spectroscopy (SERS), assembly, catalysis, and more. The
contribution of PVP to these properties as well as its removal is considered.
Ultimately, the NPs accessed through the use of PVP in colloidal syntheses are
opening new applications, and the concluding guidelines provided herein should
enable new nanostructures to be accessed facilely.
PMID- 26434728
TI - A multifunctional transparent superhydrophobic gel nanocoating with self-healing
properties.
AB - Inspired by mussels we designed a novel green superhydrophobic gel nanocoating
with good transparency and stability through a facile copolymerization reaction
at room temperature and a subsequent trimethyl silyl modified process, which is
applicable to various substrates via a simple spray process without requiring
toxic substances. Importantly, this well-designed nanocoating has rapid self
healing superhydrophobicity induced by usual organic solvents to face complicated
work conditions, which satisfies the need of daily life and can be applied in
industry as well.
PMID- 26434729
TI - Remarks on energetic conditions for positronium formation in non-polar solids.
Coupled dipole method application.
AB - A numerical program calculating the energy of a positron or/and an electron near
the free volume in solid n-alkanes has been built. The theory of the interaction
of e(+) or/and e(-) with this non-polar medium based on polarizability has been
introduced. The energy of the e(+)-e(-) pair in the bulk was compared to that
calculated when the pair forms a positronium (Ps) inside the free volume. The
calculations are based on the coupled dipole method and the dipole-dipole
interaction energy for induced dipoles is taken into account. Furthermore, a
correction for the local permittivity for the e(+)-e(-) interaction is calculated
taking into account the non-isotropic medium between them. The method is a step
toward more accurate calculations of energetic conditions during Ps formation in
matter. The possibility of the emission of the excess energy of the Ps formation
as electromagnetic radiation is discussed. It is argued that if this radiation is
observed, it can be used as a new spectroscopic tool providing information about
the microscopic properties of media.
PMID- 26434731
TI - On-surface derivatisation of aromatic molecules on graphene: the importance of
packing density.
AB - An efficient, high-throughput method for the formation of densely packed
molecular films on graphene is reported. The films exhibit high stability and
remain intact during a subsequent derivatisation reaction, offering a versatile
route for the non-covalent functionalisation of graphene.
PMID- 26434732
TI - One-Pot Relay Gold(I) and Bronsted Acid Catalysis: Cyclopenta[b]annulation of
Indoles via Hydroamination/Nazarov-Type Cyclization Cascade of Enynols.
AB - An expedient relay gold(I) and Bronsted acid catalyzed hydroamination/Nazarov
cyclization of 1-(2-aminophenyl)pent-4-en-2-ynols for the synthesis of various
polyfunctionalized cyclopenta[b]indoles is described. The synthetic utility of
this method has been demonstrated by the synthesis of a few unprecedented
pentacyclic indoles and indole-steroidal hybrids. Further, the new methodology
has been successfully applied to the enantioselective synthesis of core carbon
structure of the polyveoline family of natural products.
PMID- 26434730
TI - Improved OTU-picking using long-read 16S rRNA gene amplicon sequencing and
generic hierarchical clustering.
AB - BACKGROUND: High-throughput bacterial 16S rRNA gene sequencing followed by
clustering of short sequences into operational taxonomic units (OTUs) is widely
used for microbiome profiling. However, clustering of short 16S rRNA gene reads
into biologically meaningful OTUs is challenging, in part because nucleotide
variation along the 16S rRNA gene is only partially captured by short reads. The
recent emergence of long-read platforms, such as single-molecule real-time (SMRT)
sequencing from Pacific Biosciences, offers the potential for improved taxonomic
and phylogenetic profiling. Here, we evaluate the performance of long- and short
read 16S rRNA gene sequencing using simulated and experimental data, followed by
OTU inference using computational pipelines based on heuristic and complete
linkage hierarchical clustering. RESULTS: In simulated data, long-read sequencing
was shown to improve OTU quality and decrease variance. We then profiled 40 human
gut microbiome samples using a combination of Illumina MiSeq and Blautia-specific
SMRT sequencing, further supporting the notion that long reads can identify
additional OTUs. We implemented a complete-linkage hierarchical clustering
strategy using a flexible computational pipeline, tailored specifically for
PacBio circular consensus sequencing (CCS) data that outperforms heuristic
methods in most settings: https://github.com/oscar-franzen/oclust/ . CONCLUSION:
Our data demonstrate that long reads can improve OTU inference; however, the
choice of clustering algorithm and associated clustering thresholds has
significant impact on performance.
PMID- 26434733
TI - Unique features of human cathelicidin LL-37.
AB - Cathelicidins are antimicrobial peptides produced by humans and animals in
response to various pathogenic microbes. This review intends to provide a brief
overview of the expression, structure, properties and function of human
cathelicidin LL-37 which may be a therapeutic agent against a variety of
bacterial and viral diseases, cancers, and hard-to-heal wounds. Cathelicidins act
as a primary defense against bacteria and other pathogens in the case of
inflammation. They are able to kill bacteria and fungi, inhibit and destroy
bacterial biofilms, and possess antiviral and antiparasitics properties. They can
also play a role in angiogenesis, wound healing, and the regulation of apoptosis.
The host defense peptide LL-37 has emerged as a novel modulator of tumor growth
and metastasis in carcinogenesis of various types of cancers. LL-37 is an
antimicrobial peptide able of inducing various effects. It acts as an anti- and
pro- inflammatory factor. Cathelicidins are able to directly and selectively
destroy membranes of various microbes and cancer cells, but they do not attack
normal cells. The role of cathelicidins in cancer is double-sided. They play an
important role in killing cancer cells and may provide a new possibility for the
development of cancer therapeutics. However, they also can participate in
carcinogenesis. Due to its activity spectrum LL-37 could be applied in
pharmacotherapy. Cathelicidin peptides could serve as a template for the
development of modern anti-microbial and anti-viral drugs. LL-37 is an excellent
candidate to develop into therapeutics for infected wounds.
PMID- 26434734
TI - Retrospective volume analysis of bone remodeling after tooth extraction with and
without deproteinized bovine bone mineral insertion.
AB - OBJECTIVES: The aim of the study was to analyze volume changes of post-extractive
sockets grafted with or without deproteinized bovine bone mineral (DBBM) and a
resorbable barrier. MATERIALS AND METHODS: This retrospective analysis utilized
patients who had undergone tooth extraction. Sites, one per patient, were
allocated to two groups: post-extractive non-grafted sockets (NG) and post
extractive grafted sockets with DBBM and resorbable barrier insertion (G).
Maximal primary soft tissue closure was sought for both procedures. Before
extraction and 6 months later, three-dimensional features of the sockets (linear
indexes, areas, and volumes) and outcome variables at 6 months (volume- and
surface changes) were acquired through computer tomography scans. Intra- and
inter-group comparisons of the outcome variables were performed. Nonparametric
tests were applied with a level of significance set at P < 0.01. RESULTS: Twenty
four sites, 9 grafted and 15 ungrafted, were enrolled. Between baseline and the 6
month evaluation, significant bone volume loss, superior surface shrinkage, and
height reduction were registered for the G (72 mm(3) , 76 mm(2) , and 0.5 mm,
respectively) and the NG group (274 mm(3) , 87 mm(2) , and 1.8 mm, respectively)
with all P-values <= 0.0039. A significant difference, regarding the percentage
of the volume change, was registered between the two procedures with a volume
loss of 9.9% for the grafted sockets and 34.8% for the ungrafted ones (P-value =
0.0073). CONCLUSION: Grafting of the sockets with DBBM and a resorbable barrier
insertion seemed to reduce negative osseous remodeling in the short term when
compared to that of the ungrafted sockets.
PMID- 26434735
TI - Assessment of the cryoprotectant concentration inside a bulky organ for
cryopreservation using X-ray computed tomography.
AB - Cryoprotection of bulky organs is crucial for their storage and for subsequent
transplantation. In this work we demonstrate the capability of the X-ray computed
tomography (CT) as a non-invasive method to measure the cryoprotectant (cpa)
concentration inside a tissue or an organ, specifically for the case of dymethil
sulfoxide (Me2SO). It is remarkable that the use of Me2SO has been leader in
techniques of cells and tissues cryopreservation. Although CT technologies are
mainly based in density differences, and many cpas are alcohols with densities
similar to water, the use of very low energies as acceleration voltage (~70 kV)
and the sulfur atom in the molecule of Me2SO makes possible the visualization of
this cpa inside tissues. As result we obtain a CT signal proportional to the
Me2SO concentration with a spatial resolution up to 50 MUm in the case of our
device.
PMID- 26434736
TI - On reflexivity and the conduct of the self in everyday life: reflections on
Bourdieu and Archer.
AB - This article provides a critique of the concept of reflexivity in social theory
today and argues against the tendency to define agency exclusively in terms of
reflexivity. Margaret Archer, in particular, is highlighted as a key proponent of
this thesis. Archer argues that late modernity is characterized by reflexivity
but, in our view, this position neglects the impact of more enduring aspects of
agency, such as the routinization of social life and the role of the taken-for
granted. These concepts were pivotal to Bourdieu and Giddens' theorization of
everyday life and action and to Foucault's understanding of technologies of the
self. We offer Bourdieu's habitus as a more nuanced approach to theorizing
agency, and provide an alternative account of reflexivity. Whilst accepting that
reflexivity is a core aspect of agency, we argue that it operates to a backdrop
of the routinization of social life and operates from within and not outside of
habitus. We highlight the role of the breach in reflexivity, suggesting that it
opens up a critical window for agents to initiate change. The article suggests
caution in over-ascribing reflexivity to agency, instead arguing that achieving
reflexivity and change is a difficult and fraught process, which has emotional
and moral consequences. The effect of this is that people often prefer the status
quo, rather than to risk change and uncertainty.
PMID- 26434737
TI - Regrowth patterns and rosette attributes contribute to the differential
compensatory responses of Arabidopsis thaliana genotypes to apical damage.
AB - A plant's compensatory performance refers to its ability to maintain or increase
its reproductive output following damage. The ability of a plant to compensate
depends on numerous factors including the type, severity, frequency and timing of
damage, the environmental conditions and the plant's genotype. Upon apical
damage, a cascade of hormonal and genetic responses often produces dramatic
changes in a plant's growth, development, architecture and physiology. All else
being equal, this response is largely dependent on a plant's genotype, with
different regrowth patterns displayed by different genotypes of a given species.
In this study, we compare the architectural and growth patterns of two
Arabidopsis thaliana genotypes following apical damage. Specifically, we
characterise regrowth patterns of the genotypes Columbia-4 and Landsberg erecta,
which typically differ in their compensation to apical meristem removal. We
report that Landsberg erecta suffered reductions in the number of stems produced,
maximum elongation rate, a delay in reaching this rate, lower average rosette
quality throughout the growing period, and ultimately, less aboveground dry
biomass and seed production when damaged compared to undamaged control plants.
Columbia-4 had no reductions in any of these measures and maintained larger
rosette area when clipped relative to when unclipped. Based on the apparent
influence of the rosette on these genotypes' compensatory performances, we
performed a rosette removal experiment, which confirmed that the rosette
contributes to compensatory performance. This study provides a novel
characterisation of regrowth patterns following apical damage, with insights into
those measures having the largest effect on plant performance.
PMID- 26434738
TI - Proactive treatment with calcipotriol reduces recurrence of plaque psoriasis.
AB - Topical calcipotriol is a widely used treatment for plaque-type psoriasis
worldwide, and has been shown to improve psoriatic plaques as well as very potent
corticosteroids. However, there remains the practical question of whether
calcipotriol application should continue on healed pigmentation/depigmentation
associated with psoriatic plaques. Therefore, we conducted a pilot clinical study
to answer this question. Plaque-type psoriatic patients not receiving systemic
treatment were enrolled and treated with calcipotriol for 8 weeks (stage I) to
achieve maximum effect. The patients were then divided into two groups: group A
continued to apply calcipotriol to the entirety of the previous lesion (including
pigmentation/depigmentation) regardless of whether skin was healed or not, while
group B applied calcipotriol to the remaining lesion only. Patients were followed
for 12 weeks (stage II) and dates of plaque recurrence were recorded. A total of
29 patients (13 men, 16 women) were enrolled. During stage I, reductions in
scores for redness, induration and scale occurred in 40%, 47% and 55% of
patients, respectively. After stage II was completed, group A (n = 19) showed a
significantly better Kaplan-Meier curve of non-recurrence than group B (n = 8, P
< 0.01). The mean non-recurrence duration was 76.8 +/- 11.8 in group A and 35.0
+/- 12.0 in group B. Our study showed that applying topical calcipotriol on
seemingly healed psoriatic plaque lesions suppresses recurrence better than
applying it only on remaining plaques. This finding may be important for
instructing psoriatic patients on topical calcipotriol treatment.
PMID- 26434739
TI - Renal Denervation in Patients With Uncontrolled Hypertension and Confirmed
Adherence to Antihypertensive Medications.
AB - Renal denervation (RDN) has emerged as a potential device-based treatment for
resistant hypertension. The authors present their experience of the use of
catheter-based RDN as part of routine clinical care in two specialist
hypertension clinics. Thirty-four patients with uncontrolled hypertension
underwent RDN. All patients had ambulatory blood pressure (BP) monitoring and
directly observed medication administration prior to the procedure to exclude
white-coat hypertension and nonadherence, respectively. Overall, there was a
significant change in clinic systolic BP of -15.1 mm Hg (95% confidence interval,
-23.4 to -6.8; P=.001) and clinic diastolic BP of -6.2 mm Hg (95% confidence
interval, -11.5 to -0.9; P=.02) 6 months postprocedure, and a nonsignificant
change in daytime ambulatory BP of -5.4/-2.9 mm Hg. Eighteen patients (51.4%)
showed a significant reduction in their clinic systolic BP (>=10 mm Hg) and 16
(47%) had a significant reduction in their daytime ambulatory systolic BP (>=5 mm
Hg) at 6 months.
PMID- 26434740
TI - Enhanced Pain Sensitivity Among Individuals With Symptomatic Knee Osteoarthritis:
Potential Sex Differences in Central Sensitization.
AB - OBJECTIVE: Symptomatic knee osteoarthritis (OA) is a condition commonly
associated with increased pain, disability, and functional limitations. Given the
poor correspondence between radiographic evidence and clinical pain, central
sensitization has been implicated as a potential mechanism underlying pain
facilitation in knee OA. Sex may be a moderator of centrally mediated changes in
knee OA pain; however, few studies have systematically assessed this. Therefore,
the aim of this study was to examine differences in peripheral and central
sensitization in men and women with symptomatic knee OA, as well as to determine
whether these differences vary across age (middle age versus older age). METHODS:
Participants (n = 288) between the ages of 45 and 85 years completed a battery of
quantitative sensory pain procedures assessing sensitivity to contact heat, cold
pressor, mechanical pressure, and punctate stimuli. Differences in temporal
summation (TS) were examined, as well as measures of clinical pain and functional
performance. RESULTS: When compared to men, women exhibited greater sensitivity
to multiple pain modalities (i.e., lower heat, cold, pressure
thresholds/tolerances, greater TS of pain); however, there were no sex
differences in clinical pain, with the exception of greater widespread pain
observed in women. Although there were select age-related differences in pain
sensitivity, sex differences in pain varied minimally across the age cohort.
CONCLUSION: Overall, these findings provide evidence for greater overall
sensitivity to experimental pain in women with symptomatic knee OA compared to
men, suggesting that enhanced central sensitivity may be an important contributor
to pain in this group.
PMID- 26434741
TI - Esco2 regulates cx43 expression during skeletal regeneration in the zebrafish
fin.
AB - BACKGROUND: Roberts syndrome (RBS) is a rare genetic disorder characterized by
craniofacial abnormalities, limb malformation, and often severe mental
retardation. RBS arises from mutations in ESCO2 that encodes an acetyltransferase
and modifies the cohesin subunit SMC3. Mutations in SCC2/NIPBL (encodes a cohesin
loader), SMC3 or other cohesin genes (SMC1, RAD21/MCD1) give rise to a related
developmental malady termed Cornelia de Lange syndrome (CdLS). RBS and CdLS
exhibit overlapping phenotypes, but RBS is thought to arise through mitotic
failure and limited progenitor cell proliferation while CdLS arises through
transcriptional dysregulation. Here, we use the zebrafish regenerating fin model
to test the mechanism through which RBS-type phenotypes arise. RESULTS: esco2 is
up-regulated during fin regeneration and specifically within the blastema. esco2
knockdown adversely affects both tissue and bone growth in regenerating fins
consistent with a role in skeletal morphogenesis. esco2-knockdown significantly
diminishes cx43/gja1 expression which encodes the gap junction connexin subunit
required for cell-cell communication. cx43 mutations cause the short fin
(sof(b123) ) phenotype in zebrafish and oculodentodigital dysplasia (ODDD) in
humans. Importantly, miR-133-dependent cx43 overexpression rescues esco2
dependent growth defects. CONCLUSIONS: These results conceptually link ODDD to
cohesinopathies and provide evidence that ESCO2 may play a transcriptional role
critical for human development.
PMID- 26434743
TI - Bacillus thuringiensis subsp. israelensis producing endochitinase ChiA74Deltasp
inclusions and its improved activity against Aedes aegypti.
AB - AIMS: The objective of this study was to produce stable inclusions of chitinase
ChiA74Deltasp in Bacillus thuringiensis subsp. israelensis (Bti) and to assay its
insecticidal activity against Aedes aegypti larvae. METHODS AND RESULTS: Bti was
transformed with chiA74Deltasp regulated by its own promoter or by the strong
chimeric cytAp/STAB-SD promoter system to generate two recombinant Bti strains.
These recombinants produced their native parasporal bodies composed of Cry4Aa,
Cry4Ba, Cry11Aa and Cyt1Aa and ChiA74Deltasp inclusions, and showed a approx.
threefold increase in both endochitinase activity and viable spore count when
compared with the parental strain. Both recombinants were approximately twofold
more toxic (LC50s 8.02, 9.6 ng ml(-1) ) than parental Bti (19.8 ng ml(-1) )
against 4(th) instars of A. aegypti larvae. CONCLUSIONS: ChiA74Deltasp
inclusions, together with the insecticidal crystals and spores of Bti increased
the toxicity against A. aegypti larvae by at least twofold. SIGNIFICANCE AND
IMPACT OF THE STUDY: We report for the first time the engineering of Bti to
produce spore-parasporal body-ChiA74?sp inclusions in the same sporangium, which
are released together following autolysis. Our work lays a foundation for
engineering Bti to produce more efficacious combinations of Cry4Aa, Cry4Ba,
Cry11Aa, Cyt1Aa and chitinase inclusions.
PMID- 26434744
TI - Highlighting the problematic reliance on CD18 for diagnosing leukocyte adhesion
deficiency type 1.
AB - Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive primary
immunodeficiency, hallmarked by defective polymorphonuclear transmigration. It is
caused by mutations in the gene encoding CD18, which interfere with the CD18/CD11
heterodimerization and expression on leukocyte cell surface. LAD-1 diagnosis
rests primarily on the measurement of CD18 expression. However, CD18 measurement
entails its pitfalls. Here we present a cohort of ten LAD patients and a review
of the relevant literature illustrating the difficulties in sole reliance on CD18
measurement for initial diagnosis. These include normal range expression in some
mutations, great variability between patients with the same mutation and
subjective interpretation of results. We think there is a need for additional
markers as part of the initial LAD diagnostic algorithm. We suggest CD11a
expression, which was near absent in all patients in our cohort. The dual use of
CD18 and CD11a can increase testing sensitivity and prevent delayed diagnosis of
LAD-1.
PMID- 26434745
TI - In Vivo Evaluation of Two-Piece Implants Placed Following One-Stage and Two-Stage
Surgical Protocol in Posterior Mandibular Region. Assessment of Alterations in
Crestal Bone Level.
AB - BACKGROUND: Endosseous implants can be placed following either two-stage
technique requiring second-stage surgery or one-stage technique, which does not
involve a second surgical intervention. PURPOSE: The present study was undertaken
to evaluate and compare the changes in crestal bone level when two-piece implants
were placed in posterior mandibular region following one-stage and two-stage
surgical protocol. MATERIALS AND METHODS: A parallel group randomized prospective
study was designed in which 20 two-piece implants were placed in the posterior
mandibular region of 16 partially edentulous healthy patients following either
one-stage (Group I) or a two-stage surgical protocol (Group II). Alterations in
crestal bone level were assessed with the help of DentaScan at baseline, that is,
at the time of implant placement, third month and sixth month. RESULTS:
Nonsignificant differences were seen in both groups in terms of changes in
crestal bone level at the final evaluation. CONCLUSIONS: Hence, it could be
concluded that two-piece implants can be placed following one-stage surgical
protocol as predictably as when two-stage surgical technique is followed.
PMID- 26434742
TI - Leveraging ecological theory to guide natural product discovery.
AB - Technological improvements have accelerated natural product (NP) discovery and
engineering to the point that systematic genome mining for new molecules is on
the horizon. NP biosynthetic potential is not equally distributed across
organisms, environments, or microbial life histories, but instead is enriched in
a number of prolific clades. Also, NPs are not equally abundant in nature; some
are quite common and others markedly rare. Armed with this knowledge, random
'fishing expeditions' for new NPs are increasingly harder to justify.
Understanding the ecological and evolutionary pressures that drive the non
uniform distribution of NP biosynthesis provides a rational framework for the
targeted isolation of strains enriched in new NP potential. Additionally,
ecological theory leads to testable hypotheses regarding the roles of NPs in
shaping ecosystems. Here we review several recent strain prioritization practices
and discuss the ecological and evolutionary underpinnings for each. Finally, we
offer perspectives on leveraging microbial ecology and evolutionary biology for
future NP discovery.
PMID- 26434746
TI - Sutureless 3F Enable Valve Replacement for Pure Aortic Regurgitation.
AB - BACKGROUND AND AIM: We present our experience in the use of the sutureless valve
in patients undergoing aortic valve replacement for pure aortic regurgitation.
METHODS: Out of 167 patients who underwent sutureless aortic valve implantation
with a Medtronic 3f Enable prosthesis in our unit between March 2011 and February
2014, 12 (7.1%) received a sutureless valve for pure aortic regurgitation.
RESULTS: Mean age, logistic EuroSCORE, and left ventricular ejection fraction
were 72 +/- 5 years, 6.3 +/- 2.9%, and 52.5 +/- 15.3%, respectively. The
sutureless valve could be successfully implanted in all cases; nine patients had
a full sternotomy (associated coronary artery bypass graft in four cases and
associated mitral surgery in five), one patient had a ministernotomy, and two had
a thoracoscopic approach. Average cross-clamping and cardiopulmonary bypass times
were 90 +/- 30 and 127 +/- 51 minutes, respectively. At the outpatient
echocardiography, average mean gradient was 10.54 +/- 4.99 mmHg and a grade I-II
paravalvular leakage (PVL) was detected in the first patient of the cohort
(ministernotomy approach). At a mean follow-up of 11.1 +/- 5.5 months, average
mean gradient was 9.75 +/- 2.87 mmHg, no new PVL was detected, and the known PVL
was stable. No pacemaker implantation was required. CONCLUSIONS: Implantation of
the 3f Enable sutureless valve is technically possible with pure aortic
regurgitation in selected patients. Multicenter investigations are necessary to
assess the mid-term benefits of such a device in this subset of patients.
PMID- 26434747
TI - As I recall the beginning of the American journal of hematology forty years ago.
PMID- 26434749
TI - Melanosomes and ancient coloration re-examined: A response to Vinther 2015 (DOI
10.1002/bies.201500018).
AB - Round to elongate microbodies associated with fossil vertebrate soft tissues were
interpreted as microbial traces until 2008, when they were re-described as
remnant melanosomes - intracellular, pigment-containing eukaryotic organelles.
Since then, multiple claims for melanosome preservation and inferences of
organismal color, behavior, and physiology have been advanced, based upon the
shape and size of these microstructures. Here, we re-examine evidence for ancient
melanosomes in light of information reviewed in Vinther (2015), and literature
regarding the preservation potential of microorganisms and their exopolymeric
secretions. We: (i) address statements in Vinther's recent (2015) review that are
incorrect or which misrepresent published data; (ii) discuss the need for caution
in interpreting "voids" and microbodies associated with degraded fossil soft
tissues; (iii) present evidence that microorganisms are in many cases an equally
parsimonious source for these "voids" as are remnant melanosomes; and (iv)
suggest methods/criteria for differentiating melanosomes from microbial traces in
the fossil record.
PMID- 26434748
TI - Glucagon increases energy expenditure independently of brown adipose tissue
activation in humans.
AB - AIMS: To investigate, for a given energy expenditure (EE) rise, the differential
effects of glucagon infusion and cold exposure on brown adipose tissue (BAT)
activation in humans. METHODS: Indirect calorimetry and supraclavicular
thermography was performed in 11 healthy male volunteers before and after: cold
exposure; glucagon infusion (at 23 degrees C); and vehicle infusion (at 23
degrees C). All volunteers underwent (18)F-fluorodeoxyglucose ((18)F-FDG)
positron emission tomography (PET)/CT scanning with cold exposure. Subjects with
cold-induced BAT activation on (18)F-FDG PET/CT (n = 8) underwent a randomly
allocated second (18)F-FDG PET/CT scan (at 23 degrees C), either with glucagon
infusion (n = 4) or vehicle infusion (n = 4). RESULTS: We observed that EE
increased by 14% after cold exposure and by 15% after glucagon infusion (50
ng/kg/min; p < 0.05 vs control for both). Cold exposure produced an increase in
neck temperature (+0.44 degrees C; p < 0.001 vs control), but glucagon infusion
did not alter neck temperature. In subjects with a cold-induced increase in the
metabolic activity of supraclavicular BAT on (18)F-FDG PET/CT, a significant rise
in the metabolic activity of BAT after glucagon infusion was not detected. Cold
exposure increased sympathetic activation, as measured by circulating
norepinephrine levels, but glucagon infusion did not. CONCLUSIONS: Glucagon
increases EE by a similar magnitude compared with cold activation, but
independently of BAT thermogenesis. This finding is of importance for the
development of safe treatments for obesity through upregulation of EE.
PMID- 26434750
TI - Lactobacillus rhamnosus GG SpaC pilin subunit binds to the carbohydrate moieties
of intestinal glycoconjugates.
AB - Lactobacillus rhamnosus GG (LGG) is a well-established probiotic strain. The
beneficial properties of this strain are partially dependent on its prolonged
residence in the gastrointestinal tract, and are likely influenced by its
adhesion to the intestinal mucosa. The pilin SpaC subunit, located within the Spa
pili structure, is the most well studied LGG adhesion factor. However, the
binding epitopes of SpaC remain largely unknown. The aim of this study was to
evaluate the binding properties of SpaC to the carbohydrate moieties of
intestinal glycoconjugates using a recombinant SpaC protein. In a competitive
enzyme-linked immunosorbent assay, SpaC binding was markedly reduced by addition
of purified mucin and the mucin oligosaccharide fraction. Histochemical staining
revealed that the binding of SpaC was drastically reduced by periodic acid
treatment. Moreover, in the surface plasmon resonance-based Biacore assay, SpaC
bound strongly to the carbohydrate moieties containing beta-galactoside at the
non-reducing terminus of glycolipids. We here provide the first demonstration
that SpaC binds to the oligosaccharide chains of mucins, and that the
carbohydrate moieties containing beta-galactoside at the non-reducing termini of
glycoconjugates play a crucial role in this binding. Our results demonstrate the
importance of carbohydrates of SpaC for mucus interactions.
PMID- 26434751
TI - Funnel compression suture: a conservative procedure to control postpartum
bleeding from the lower uterine segment.
AB - Bleeding from the lower uterine segment (LUS) during caesarean section remains a
life-threatening obstetric problem, particularly in women with placenta praevia
or partial placenta accreta in the LUS. Various conservative measures for the
surgical treatment of postpartum haemorrhage have been studied for decades. In
this paper we describe a funnel compression suture to staunch intractable
bleeding from LUS for placenta praevia accreta. The suture brings the anterior
and posterior walls of the LUS together using absorbable thread and was
successful in the overwhelming majority of women. It is an easy, safe and
effective conservative surgical treatment to stop severe bleeding of the LUS.
PMID- 26434752
TI - Impact of pharmacist involvement in the transitional care of high-risk patients
through medication reconciliation, medication education, and postdischarge call
backs (IPITCH Study).
AB - BACKGROUND: Previous data suggest that direct pharmacist interaction with
patients through medication reconciliation, discharge counseling, and
postdischarge phone calls decreases the number of adverse drug events (ADEs) and
plays an overall positive role in transitional care. Previous studies have
evaluated pharmacist involvement in improving transitional care, but these
studies did not include multiple postdischarge follow-up phone calls. OBJECTIVES:
The objectives of this study were to assess the impact of pharmacist involvement
in transitions of care as measured by decreased medication errors (MEs) and ADEs,
patients' knowledge related to communication about their medications as measured
by improvement in the Hospital Consumer Assessment of Healthcare Providers and
Systems (HCAHPS) scores, and 30-day all-cause inpatient readmissions and
emergency department (ED) visits. METHODS: This was a prospective, randomized,
single-period longitudinal study that occurred from November 2012 through June
2013 at an urban, tertiary, academic medical center. Patients admitted to 2
designated internal medicine units on high-risk medications or with greater than
3 prescription medications upon discharge were included for randomization. The
control group received the usual hospital standard of care. The study group
received face-to-face medication reconciliation, a patient-specific
pharmaceutical care plan, discharge counseling, and postdischarge phone calls on
days 3, 14, and 30 to provide education and assess study endpoints. RESULTS: A
total of 278 patients were included in the final analysis, with 141 in the
control group and 137 in the study group. Fifty-five patients (39%) in the
control arm experienced an inpatient readmission or ED visit within 30-days
postdischarge compared to 34 patients (24.8%) in the study arm (P = 0.01).
Eighteen patients (12.8%) in the control group experienced an ADEs or MEs
compared to 11 patients (8%) in the study group (P > 0.05). The HCAHPS scores
during the study period showed a 9% improvement for the assessed questionnaire
domain (P > 0.05). CONCLUSIONS: This study demonstrated that pharmacist
involvement in hospital discharge transitions of care had a positive impact on
decreasing composite inpatient readmissions and ED visits. Statistically
significant difference in medication-related events and HCAHPS scores were not
observed. Patients with moderately complex medication regimens benefited from a
continuity of care involving a pharmacy team during transitions in care.
PMID- 26434753
TI - Droplet digital polymerase chain reaction assay for screening of ESR1 mutations
in 325 breast cancer specimens.
AB - Droplet digital polymerase chain reaction (ddPCR), which could perform thousands
of PCRs on a nanoliter scale simultaneously, would be an attractive method to
massive parallel sequencing for identifying and studying the significance of low
frequency rare mutations. Recent evidence has shown that the key potential
mechanisms of the failure of aromatase inhibitors-based therapy involve
identifying activating mutations affecting the ligand-binding domain of the ESR1
gene. Therefore, the detection of ESR1 mutations may be useful as a biomarker
predicting an effect of the treatment. We aimed to develop a ddPCR-based method
for the sensitive detection of ESR1 mutations in 325 breast cancer specimens, in
which 270 primary and 55 estrogen receptor-positive (ER+) metastatic breast
cancer (MBC) specimens. Our ddPCR assay could detect the ESR1 mutant molecules
with low concentration of 0.25 copies/MUL. According to the selected cutoff, ESR1
mutations occurred in 7 (2.5%) of 270 primary breast cancer specimens and in 11
(20%) of 55 ER+ MBC specimens. Among the 11 MBC specimens, 5 specimens (45.5%)
had the most common ESR1 mutation, Y537S, 4 specimens (36.3%) each had D538G,
Y537N, and Y537C. Interestingly, 2 patients had 2 ESR1 mutations, Y537N/D538G and
Y537S/Y537C, and 2 patients had 3 ESR1 mutations, Y537S/Y537N/D538G. Biopsy was
performed in heterochrony in 8 women twice. In 8 women, 4 women had primary
breast cancer and MBC specimens and 4 women had 2 specimens when treatment was
failure. Four of these 8 women acquired ESR1 mutation, whereas no ESR1 mutation
could be identified at first biopsy. ddPCR technique could be a promising tool
for the next-generation sequencing-free precise detection of ESR1 mutations in
endocrine therapy resistant cases and may assist in determining the treatment
strategy.
PMID- 26434754
TI - The association between total leukocyte count and longevity: Evidence from
longitudinal and cross-sectional data.
AB - The aim of the study was to evaluate the relationship between age-dependent
changes in total leukocyte count (TLC) and certain selected differential counts
expressed as frequencies (granulocytes, band cells, eosinophils, lymphocytes, and
monocytes) and longevity in physically healthy men and women aged 45+.
Longitudinal data on cell counts from 142 subjects (68 men and 74 women; all aged
45-70 and examined for 25 years) were compared with cross-sectional data from 225
subjects (113 men and 112 women; this group was divided into four categories of
average lifespan; i.e.: 53, 63, 68, and 76+ years of age). ANOVA, t-test, and
regression analysis were employed. Secular changes in leukocyte count were
controlled. Men had continuously higher TLC compared with women. Moreover, sex
differences in patterns of changes with age were found. The longitudinal
assessment revealed a U-shaped pattern of changes in TLC in men (y=0.0026x(2)
0.2866x+14.4374; R(2)=0.852) and women (y=0.0048x(2)-0.5386x+20.922; R(2)=0.938),
whereas the cross-sectional comparison showed an inverted U-shaped pattern in men
(y=-0.0021x(2)+0.2421x; R(2)=0.417) and women (y=-0.0017x(2)+0.2061x;
R(2)=0.888). In general, the comparison of longitudinal and cross-sectional data
on changes with age in TLC indicates that longevity favors individuals with lower
yet normal TLC and this correlation is more pronounced in men. In conclusion, our
findings are in line with previous longitudinal studies of aging and suggest that
lower TLC within the normal range (4.0-10.0 * 10(3)MUL(-1)) can be a useful
predictor of longevity in physically healthy individuals.
PMID- 26434755
TI - Changes in collagens and chondrocytes in the temporomandibular joint cartilage in
growing rats fed a liquid diet.
AB - The temporomandibular joint (TMJ) of growing rats fed a soft diet is reported to
be smaller in size and to have thinner condyle and glenoid fossa cartilage than
rats fed a solid diet. The aim of this study was to determine the effect of a
soft diet on the collagens and chondrocytes in the growing TMJ cartilage. Forty
eight male Wistar rats were divided into a control group fed a solid diet and an
experimental group fed a liquid diet for 1-8 weeks. After the experimental
period, the TMJs were harvested and examined histologically,
immunohistochemically for collagen types I, II, and X, and with transmission
electron microscopy. The condylar cartilage in the experimental rats showed weak
immunoreactions for three types of collagens compared with the controls. The
ultrastructure had fewer fine collagen fibrils in the experimental rats compared
with that of the controls. The glenoid fossa cartilage in the experimental rats
showed narrower Alcian blue-positive areas than the control staining. The
immunoreactions for three types of collagen in the experimental rats were also
weaker than those of the controls. The chondrocytes in the experimental rats
appeared dark, had extended thin cytoplasmic processes, and had formed gap
junctions, as assessed by transmission electron microscopy. Fewer fine collagen
fibrils, but thick bands of collagen fibrils were observed in the glenoid fossa
of the experimental cartilage. The results of the present study showed that a
liquid diet had deleterious effects on the quality and quantity of collagens and
chondrocytes in the TMJ cartilage in growing rats.
PMID- 26434756
TI - Morphological aspects and physical properties of enamel and dentine of Sus
domesticus: A tooth model in laboratory research.
AB - This study aims to describe and analyze morphological and physical properties of
deciduous teeth of Sus domesticus. Ultrastructural analysis, mineral composition
and microhardness of enamel and dentine tissues were performed on 10 skulls of S.
domesticus. External anatomic characteristics and the internal anatomy of the
teeth were also described. Data regarding microhardness and ultrastructural
analysis were subjected to statistical tests. For ultrastructural analysis, we
used the analysis of variance (ANOVA) with Tukey's post hoc (p<=0.05) test. In
the analysis of microhardness, the difference between the enamel and dentine
tissues was analyzed by a Student's t test. Values were expressed as mean with
standard error. The results of ultrastructural analysis showed the presence of an
enamel prism pattern. A dentinal tubule pattern was also observed, with a larger
diameter in the pulp chamber and the cervical third, in comparison to middle and
apical thirds. We observed an average microhardness of 259.2kgf/mm(2) for enamel
and 55.17kgf/mm(2) for dentine. In porcine enamel and dentine, the chemical
elements Ca and P showed the highest concentration. The analysis of internal
anatomy revealed the presence of a simple root canal system and the occurrence of
main canals in the roots. The observed features are compatible with the
functional demand of these animals, following a pattern very similar to that seen
in other groups of mammals, which can encourage the development of research using
dental elements from the pig as a substitute for human teeth in laboratory
research.
PMID- 26434757
TI - Centric slide in different Angle's classes of occlusion.
AB - The purpose of this study was to test the possible differences in centric slide
values between different Angle's classes of occlusion. The study included 98
participants divided into four groups: Angle's class I, Angle's class II,
subdivision 1, Angle's class II, subdivision 2 and Angle's class III. All
recordings were obtained using an ultrasound jaw tracking device with six degrees
of freedom. The distance between the maximum intercuspation (reference position)
and the centric occlusion was recorded at the condylar level. Anteroposterior,
superoinferior and transversal distance of the centric slide were calculated for
each participant, and the data were statistically analyzed (analysis of variance
and Newman-Keuls post hoc test). No statistically significant difference was
found in the anteroposterior and transversal distance of the centric slide
between tested groups, while Angle's class II, subdivision 2 showed smaller
vertical amount of the centric slide compared to Angle's class I and class II,
subdivision 1. None of the 98 participants showed coincidence of centric
occlusion and maximum intercuspation. Our results suggest that coincidence of the
maximum intercuspation with the centric occlusion should not be expected. Smaller
extent of the vertical distance of the centric slide could be morphological and a
functional expression characteristic of the Angle's class II, subdivision 2.
PMID- 26434758
TI - Uptake of ferromagnetic carbon-encapsulated metal nanoparticles in endothelial
cells: influence of shear stress and endothelial activation.
AB - AIM: Magnetic field guided drug targeting holds promise for more effective cancer
treatment. Intravascular application of magnetic nanoparticles, however, bears
the risk of potentially important, yet poorly understood side effects, such as
off-target accumulation in endothelial cells. MATERIALS & METHODS: Here, we
investigated the influence of shear stress (0-3.22 dyn/cm(2)), exposure time (5
30 min) and endothelial activation on the uptake of ferromagnetic carbon
encapsulated iron carbide nanomagnets into endothelial cells in an in vitro flow
cell model. RESULTS: We found that even moderate shear stresses typically
encountered in the venous system strongly reduce particle uptake compared with
static conditions. Interestingly, a pronounced particle uptake was observed in
inflamed endothelial cells. CONCLUSION: This study highlights the importance of
relevant exposure scenarios accounting for physiological conditions when studying
particle-cell interactions as, for example, shear stress and endothelial
activation are major determinants of particle uptake. Such considerations are of
particular importance with regard to successful translation of in vitro findings
into (pre-)clinical end points.
PMID- 26434759
TI - The association of serum sodium and chloride levels with blood pressure and
estimated glomerular filtration rate.
AB - BACKGROUND: High serum sodium (sNa) concentrations may be associated with
hypertension, which deteriorates kidney function. However, it is equivocal
whether high sNa concentrations are associated with impaired kidney function
independently of blood pressure (BP) or serum chloride (sCl). Therefore, we
addressed this issue in an apparently healthy population. METHODS: Clinical
variables including estimated glomerular filtration rate (eGFR) were examined in
3603 men and women (aged 25-75 years) who underwent health-screening check-ups.
sNa concentrations were classified into five categories. RESULTS: Most
parameters, including age and BP, increased with increasing sNa, whereas eGFR
decreased. Logistic regression analysis showed that, compared with low-normal sNa
(<= 140 mEq/l), high sNa (>= 144 mEq/l) was significantly associated with
elevated BP (>= 130/85 mmHg) even after adjustment for blood hematocrit, eGFR,
serum potassium (sK) concentration and sCl. The highest sNa category was
significantly associated with reduced eGFR (< 60 ml/min/1.73 m(2)) independently
of elevated BP. Unlike adjustment for sK, adjustment for sCl strengthened the
association between high sNa and elevated BP but attenuated the association
between high sNa and reduced eGFR. CONCLUSIONS: These results suggest that high
sNa concentrations, even within the normal range, are independently associated
with elevated BP and impaired kidney function. These associations may be
substantially modified by sCl.
PMID- 26434760
TI - Site Covalent Modification of Methionyl Peptides for the Production of FRET
Complexes.
AB - Flax cyclic peptides (orbitides, linusorbs (LOs)) [1-8-NalphaC],[1-MetO2]
linusorb B1 ([MetO2]-LO1) and [1-9-NalphaC],[1-MetO2]-linusorb B2 ([MetO2]-LO2)
are biologically active. These LOs lack active nuclei commonly used in peptide
modification. We have developed reactions to activate methionine methyl sulphide
to produce stable derivatives. In these reactions, LOs are converted to sulfonium
intermediates and subsequently to derivatives containing active nuclei while
preserving their fundamental structures. The reaction conditions preserved cyclic
peptide fundamental structure and organic solvent solubility. [Met]-LO1 and [Met]
LO2 analogues containing activated groups (-CN, -COOEt, and -NH2 ) in the form of
methionine, methionine (S)-oxide, and methionine (S,S)-dioxide amino acids were
synthesized and characterized by LCMS and 1D and 2D NMR spectroscopy. Coumarin
orbitide complexes produced in this manner bind Eu(3+) yielding FRET compounds
that absorb energy through coumarin antennae and emit photons at lanthanide
wavelengths.
PMID- 26434766
TI - Design and fabrication of a metastable beta-type titanium alloy with ultralow
elastic modulus and high strength.
AB - Titanium and its alloys have become the most attractive implant materials due to
their high corrosion resistance, excellent biocompatibility and relatively low
elastic modulus. However, the current Ti materials used for implant applications
exhibit much higher Young's modulus (50 ~ 120 GPa) than human bone (~30 GPa).
This large mismatch in the elastic modulus between implant and human bone can
lead to so-called "stress shielding effect" and eventual implant failure.
Therefore, the development of beta-type Ti alloys with modulus comparable to that
of human bone has become an ever more pressing subject in the area of advanced
biomedical materials. In this study, an attempt was made to produce a bone
compatible metastable beta-type Ti alloy. By alloying and thermo-mechanical
treatment, a metastable beta-type Ti-33Nb-4Sn (wt. %) alloy with ultralow Young's
modulus (36 GPa, versus ~30 GPa for human bone) and high ultimate strength (853
MPa) was fabricated. We believe that this method can be applied to developing
advanced metastable beta-type titanium alloys for implant applications. Also,
this approach can shed light on design and development of novel beta-type
titanium alloys with large elastic limit due to their high strength and low
elastic modulus.
PMID- 26434764
TI - Extensive weight loss reveals distinct gene expression changes in human
subcutaneous and visceral adipose tissue.
AB - Weight loss has been shown to significantly improve Adipose tissue (AT) function,
however changes in AT gene expression profiles particularly in visceral AT (VAT)
have not been systematically studied. Here, we tested the hypothesis that
extensive weight loss in response to bariatric surgery (BS) causes AT gene
expression changes, which may affect energy and lipid metabolism, inflammation
and secretory function of AT. We assessed gene expression changes by whole genome
expression chips in AT samples obtained from six morbidly obese individuals, who
underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en
Y gastric bypass as second step surgery after 12 +/- 2 months. Global gene
expression differences in VAT and subcutaneous (S)AT were analyzed through the
use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered
gene expressions were PCR-validated in 16 individuals, which also underwent a two
step surgery intervention. We found increased expression of cell death-inducing
DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat
depots in response to significant weight loss. We observed that expression of the
genes associated with metabolic reactions involved in NAD+, glutathione and
branched chain amino acid metabolism are significantly increased in AT depots
after surgery-induced weight loss.
PMID- 26434765
TI - Real-time Detection of Breast Cancer Cells Using Peptide-functionalized
Microcantilever Arrays.
AB - Ligand-directed targeting and capturing of cancer cells is a new approach for
detecting circulating tumor cells (CTCs). Ligands such as antibodies have been
successfully used for capturing cancer cells and an antibody based system
(CellSearch((r))) is currently used clinically to enumerate CTCs. Here we report
the use of a peptide moiety in conjunction with a microcantilever array system to
selectively detect CTCs resulting from cancer, specifically breast cancer. A
sensing microcantilever, functionalized with a breast cancer specific peptide 18
4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB
231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells.
The peptide-functionalized microcantilever allowed efficient capture and
detection of cancer cells in MCF7 spiked human blood samples emulating CTCs in
human blood. A detection limit of 50-100 cancer cells mL(-1) from blood samples
was achieved with a capture yield of 80% from spiked whole blood samples. The
results emphasize the potential of peptide 18-4 as a novel peptide for capturing
and detecting cancer cells in conjunction with nanomechanical cantilever
platform. The reported peptide-based cantilever platform represents a new
analytical approach that can lead to an alternative to the various detection
platforms and can be leveraged to further study CTCs.
PMID- 26434767
TI - Rapid low dose electron tomography using a direct electron detection camera.
AB - We demonstrate the ability to record a tomographic tilt series containing 3487
images in only 3.5 s by using a direct electron detector in a transmission
electron microscope. The electron dose is lower by at least one order of
magnitude when compared with that used to record a conventional tilt series of
fewer than 100 images in 15-60 minutes and the overall signal-to-noise ratio is
greater than 4. Our results, which are illustrated for an inorganic nanotube, are
important for ultra-low-dose electron tomography of electron-beam-sensitive
specimens and real-time dynamic electron tomography of nanoscale objects with sub
ms temporal resolution.
PMID- 26434768
TI - Extended storage and glucose exhaustion are associated with apoptotic changes in
platelets stored in additive solution.
AB - BACKGROUND: The storage of platelets (PLTs) in additive solution (AS) may
facilitate improved PLT quality and possibly extension of the PLT shelf life. A
minimum amount of plasma is required when PLTs are stored in AS, as a source of
glucose. The aim of this study was to assess the effect of reducing the plasma
carryover to 20% on PLT quality when stored in SSP+ for an extended period. STUDY
DESIGN AND METHODS: Using a pool-and-split design, buffy coat-derived PLTs were
stored in either 30% plasma/SSP+ or 20% plasma/SSP+. In vitro analyses were
carried out to Day 10. Metabolites and markers of PLT activation and apoptosis
were measured using a blood gas analyzer and flow cytometry. PLT apoptotic
protein expression was investigated by Western blotting. RESULTS: Glucose
exhaustion occurred in the 20% plasma group between Day 7 and Day 10. The surface
expression of P-selectin and PAC-1 was comparable on Day 10 in both groups,
suggesting that the PLTs were not activated. However, the exposure of
phosphatidylserine and the number of phosphatidylserine-positive microparticles
were significantly higher in the 20% group on Day 10. The expression of the
proapoptotic proteins Bak, Bax, and cleaved caspase-3 were higher in the 20%
plasma group by Day 7 of storage, compared to the 30% plasma group. CONCLUSION:
Exhaustion of glucose was associated with a proapoptotic phenotype. Results such
as these should be considered before extending the PLT shelf life beyond 7 days,
particularly when stored in ASs lacking glucose with low plasma carryover.
PMID- 26434769
TI - The enhanced information flow from visual cortex to frontal area facilitates
SSVEP response: evidence from model-driven and data-driven causality analysis.
AB - The neural mechanism of steady-state visual evoked potentials (SSVEP) is still
not clearly understood. Especially, only certain frequency stimuli can evoke
SSVEP. Our previous network study reveals that 8 Hz stimulus that can evoke
strong SSVEP response shows the enhanced linkage strength between frontal and
visual cortex. To further probe the directed information flow between the two
cortex areas for various frequency stimuli, this paper develops a causality
analysis based on the inversion of double columns model using particle swarm
optimization (PSO) to characterize the directed information flow between visual
and frontal cortices with the intracranial rat electroencephalograph (EEG). The
estimated model parameters demonstrate that the 8 Hz stimulus shows the enhanced
directional information flow from visual cortex to frontal lobe facilitates SSVEP
response, which may account for the strong SSVEP response for 8 Hz stimulus.
Furthermore, the similar finding is replicated by data-driven causality analysis.
The inversion of neural mass model proposed in this study may be helpful to
provide the new causality analysis to link the physiological model and the
observed datasets in neuroscience and clinical researches.
PMID- 26434770
TI - An assessment of the amount of untapped fold level novelty in under-sampled areas
of the tree of life.
AB - Previous studies of protein fold space suggest that fold coverage is plateauing.
However, sequence sampling has been -and remains to a large extent- heavily
biased, focusing on culturable phyla. Sustained technological developments have
fuelled the advent of metagenomics and single-cell sequencing, which might
correct the current sequencing bias. The extent to which these efforts affect
structural diversity remains unclear, although preliminary results suggest that
uncultured organisms could constitute a source of new folds. We investigate to
what extent genomes from uncultured and under-sampled phyla accessed through
single cell sequencing, metagenomics and high-throughput culturing efforts have
the potential to increase protein fold space, and conclude that i) genomes from
under-sampled phyla appear enriched in sequences not covered by current protein
family and fold profile libraries, ii) this enrichment is linked to an excess of
short (and possibly partly spurious) sequences in some of the datasets, iii) the
discovery rate of novel folds among sequences uncovered by current fold and
family profile libraries may be as high as 36%, but would ultimately translate
into a marginal increase in global discovery of novel folds. Thus, genomes from
under-sampled phyla should have a rather limited impact on increasing coarse
grained tertiary structure level novelty.
PMID- 26434771
TI - Advice, authority and autonomy in shared decision-making in antenatal screening:
the importance of context.
AB - Shared decision-making (SDM) has been widely advocated across many branches of
healthcare, yet there is considerable debate over both its practical application
and how it should be examined or assessed. More recent discussions of SDM have
highlighted the important of context, both internal and external to the
consultation, with a recognition that decisions cannot be understood in
isolation. This paper uses conversation analysis (CA) to examine how decision
making is enacted in the context of antenatal screening consultations in Hong
Kong. Building on previous CA work (Collins et al. , Toerien et al. 2013), we
show that, whilst previously identified formats are used here to present the need
for a decision, the overriding basis professionals suggest for actually making a
decision in this context is the level of worry or concern a pregnant woman holds
about potential foetal abnormality. Professionals take an unknowing 'epistemic
stance' (Heritage ) towards this worry, and hence step back from involvement in
decision-making. We argue that this is linked to the non-directive ethos that
prevails in antenatal screening services, and suggest that more research is
needed to understand how the enactment of SDM is affected by wider professional
contexts and parameters.
PMID- 26434772
TI - Molecular Anion Hydrogen Bonding Dynamics in Aqueous Solution.
AB - The dynamic nature of hydrogen bonding between a molecular anion, selenocyanate
(SeCN(-)), and water in aqueous solution (D2O) is addressed using FT-IR
spectroscopy, two-dimensional infrared (2D IR) vibrational echo spectroscopy, and
polarization selective IR pump-probe (PSPP) experiments performed on the CN
stretching mode. The CN absorption spectrum is asymmetric with a wing on the low
frequency (red) side of the line in contrast to the spectrum in the absence of
hydrogen bonding. It is shown that the red wing is the result of an increase in
the CN stretch transition dipole moment due to the effect of hydrogen bonding
(non-Condon effect). This non-Condon effect is similar in nature to observations
on pure water and other nonionic systems where hydrogen bonding enhances the
extinction coefficient. The 2D IR measurements of spectral diffusion (solvent
structural evolution) yield a time constant of 1.5 ps, which is within error the
same as that of the OH stretch of HOD in D2O (1.4 ps). The orientational
relaxation of SeCN(-) measured by PSPP experiments is long (4.04 ps) compared to
the spectral diffusion time. The population decay at or near the absorption line
center is a single-exponential decay of 37.4 +/- 0.3 ps, the vibrational
lifetime. However, on the red side of the line the decay is biexponential with a
low amplitude, fast component; on the blue side of the line there is a low
amplitude, fast growth followed by the lifetime decay. Both of the fast
components have 1.5 ps time constants, which is the spectral diffusion time. The
fast components of the population decays are the results of the non-Condon effect
that causes the red side of the line to be over pumped by the pump pulse.
Spectral diffusion then produces the fast decay component on the red side of the
line and the growth on the blue side of the line as the excess initial population
on the red side produces a net population flow from red to blue.
PMID- 26434773
TI - Maternal morbid obesity: financial implications of weight management.
AB - The objective of this study was to evaluate health outcomes and costs of
pregnancies complicated by extreme maternal obesity (class III obesity, body mass
index >= 40). We conducted a retrospective case-control descriptive study
comparing extremely obese women (cases) and their infants with randomly selected
controls. Health outcomes were obtained from the medical records and costs from
billing data. Total costs for each mother-infant dyad were calculated. Compared
with 85 controls, the 82 cases experienced higher morbidity, higher costs and
prolonged hospital stay. However, 26% of cases maintained or lost weight during
pregnancy, whereas none of the controls maintained or lost weight during
pregnancy. When mother/infant dyads were compared on costs, case subjects who
maintained or lost weight experienced lower costs than those who gained weight.
Neonatal intensive care consumed 78% of total hospital costs for infants of the
obese women who gained weight, but only 48% of costs for infants of obese women
who maintained or lost weight. For extremely obese women, weight management
during pregnancy was achievable, resulted in healthier neonatal outcomes and
reduced perinatal healthcare costs.
PMID- 26434774
TI - Highly Stable and Tunable Chemical Doping of Multilayer WS2 Field Effect
Transistor: Reduction in Contact Resistance.
AB - The development of low resistance contacts to 2D transition-metal dichalcogenides
(TMDs) is still a big challenge for the future generation field effect
transistors (FETs) and optoelectronic devices. Here, we report a chemical doping
technique to achieve low contact resistance by keeping the intrinsic properties
of few layers WS2. The transfer length method has been used to investigate the
effect of chemical doping on contact resistance. After doping, the contact
resistance (Rc) of multilayer (ML) WS2 has been reduced to 0.9 kOmega.MUm. The
significant reduction of the Rc is mainly due to the high electron doping
density, thus a reduction in Schottky barrier height, which limits the device
performance. The threshold voltage of ML-WS2 FETs confirms a negative shift upon
the chemical doping, as further confirmed from the positions of E(1)2g and A1g
peaks in Raman spectra. The n-doped samples possess a high drain current of 65
MUA/MUm, with an on/off ratio of 1.05 * 10(6) and a field effect mobility of 34.7
cm(2)/(V.s) at room temperature. Furthermore, the photoelectric properties of
doped WS2 flakes were also measured under deep ultraviolet light. The potential
of using LiF doping in contact engineering of TMDs opens new ways to improve the
device performance.
PMID- 26434775
TI - The Many Faces of Heterogeneous Ice Nucleation: Interplay Between Surface
Morphology and Hydrophobicity.
AB - What makes a material a good ice nucleating agent? Despite the importance of
heterogeneous ice nucleation to a variety of fields, from cloud science to
microbiology, major gaps in our understanding of this ubiquitous process still
prevent us from answering this question. In this work, we have examined the
ability of generic crystalline substrates to promote ice nucleation as a function
of the hydrophobicity and the morphology of the surface. Nucleation rates have
been obtained by brute-force molecular dynamics simulations of coarse-grained
water on top of different surfaces of a model fcc crystal, varying the water
surface interaction and the surface lattice parameter. It turns out that the
lattice mismatch of the surface with respect to ice, customarily regarded as the
most important requirement for a good ice nucleating agent, is at most desirable
but not a requirement. On the other hand, the balance between the morphology of
the surface and its hydrophobicity can significantly alter the ice nucleation
rate and can also lead to the formation of up to three different faces of ice on
the same substrate. We have pinpointed three circumstances where heterogeneous
ice nucleation can be promoted by the crystalline surface: (i) the formation of a
water overlayer that acts as an in-plane template; (ii) the emergence of a
contact layer buckled in an ice-like manner; and (iii) nucleation on compact
surfaces with very high interaction strength. We hope that this extensive
systematic study will foster future experimental work aimed at testing the
physiochemical understanding presented herein.
PMID- 26434777
TI - Crystal Perfection of Particle Monolayer at the Air-Water Interface.
AB - Crystal growth in colloidal particle monolayers fabricated by Langmuir-Blodgett
method on 4 in. sapphire wafers was investigated under the condition of two
techniques, that is, ultrasonic annealing at 1.2 to 1.5 MHz and barrier-sway
process at 0.2 to 0.5 Hz. Significant increases of the ordered area were obtained
by the both techniques and more than 60 times growth was confirmed. The remaining
crystal defects after the growth were categorized as grain boundary, vacancy, and
line defect. Both techniques exhibited different features regarding the component
ratio of the defects, and different mechanisms for the reorientation of particles
are discussed. The driving force of these re-orientations is thought to be
associated with the 2D Ostwald ripening of colloidal crystals.
PMID- 26434776
TI - Triomics Analysis of Imatinib-Treated Myeloma Cells Connects Kinase Inhibition to
RNA Processing and Decreased Lipid Biosynthesis.
AB - The combination of metabolomics, lipidomics, and phosphoproteomics that
incorporates triple stable isotope labeling by amino acids in cell culture
(SILAC) protein labeling, as well as (13)C in vivo metabolite labeling, was
demonstrated on BCR-ABL-positive H929 multiple myeloma cells. From 11 880
phosphorylation sites, we confirm that H929 cells are primarily signaling through
the BCR-ABL-ERK pathway, and we show that imatinib treatment not only
downregulates phosphosites in this pathway but also upregulates phosphosites on
proteins involved in RNA expression. Metabolomics analyses reveal that BCR-ABL
ERK signaling in H929 cells drives the pentose phosphate pathway (PPP) and RNA
biosynthesis, where pathway inhibition via imatinib results in marked PPP
impairment and an accumulation of RNA nucleotides and negative regulation of
mRNA. Lipidomics data also show an overall reduction in lipid biosynthesis and
fatty acid incorporation with a significant decrease in lysophospholipids. RNA
immunoprecipitation studies confirm that RNA degradation is inhibited with short
imatinib treatment and transcription is inhibited upon long imatinib treatment,
validating the triomics results. These data show the utility of combining mass
spectrometry-based "-omics" technologies and reveals that kinase inhibitors may
not only downregulate phosphorylation of their targets but also induce metabolic
events via increased phosphorylation of other cellular components.
PMID- 26434779
TI - Cellulose Nanocrystal Microcapsules as Tunable Cages for Nano- and
Microparticles.
AB - We demonstrate the fabrication of highly open spherical cages with large through
pores using high aspect ratio cellulose nanocrystals with "haystack" shell
morphology. In contrast to traditional ultrathin shell polymer microcapsules with
random porous morphology and pore sizes below 10 nm with limited molecular
permeability of individual macromolecules, the resilient cage-like microcapsules
show a remarkable open network morphology that facilitates across-shell transport
of large solid particles with a diameter from 30 to 100 nm. Moreover, the
transport properties of solid nanoparticles through these shells can be pH
triggered without disassembly of these shells. Such behavior allows for the
controlled loading and unloading of solid nanoparticles with much larger
dimensions than molecular objects reported for conventional polymeric
microcapsules.
PMID- 26434778
TI - Association Between ESR1 PvuII, XbaI, and P325P Polymorphisms and Breast Cancer
Susceptibility: A Meta-Analysis.
AB - BACKGROUND: Breast cancer is one of the leading causes of cancer-related deaths
for women. Numerous studies have shown that single-nucleotide polymorphisms
(SNPs) on the ESR1 gene are associated to this disease. However, data and
conclusions are inconsistent and controversial. MATERIAL AND METHODS: To
investigate the association between PvuII (rs2234693), XbaI (rs9340799) and P325P
(rs1801132) polymorphisms of ESR1 gene with the risk of breast cancer under
different population categorizations, we searched multiple databases for data
collection, and performed the meta-analysis on a total of 25 case-control
studies. Three different comparison models - dominant model, recessive model, and
homozygote comparison model - were applied to evaluate the association. RESULTS:
Our results indicated that people with TT+TC or TT genotype were at a greater
risk of developing breast cancer than those with CC genotype in the PvuII
polymorphism. While for XbaI and P325P polymorphisms, no significance was found
using any of the 3 models. Furthermore, the data were also stratified into
different subgroups according to the ethnicity (white or Asian) and source of
controls (hospital-based or population-based), and separate analyses were
conducted to assess the association. The ethnicity subgroup assessment showed
that the higher risk of breast cancer for TT genotype of PvuII polymorphism than
CC genotype only occurred in Asian people, but not in white populations. For the
source-stratified subgroup analysis, significant association suggested that
people with TT + TC genotype were at a greater risk of developing breast cancer
than those with CC genotype in the hospital-based subgroup. CONCLUSIONS: Thus,
this meta-analysis clarified the inconsistent conclusions from previous studies,
conducted analyses for the entire population as well as for different subgroups
using diverse population categorization strategies, and has the potential to help
provide a personalized risk estimate for breast cancer susceptibility.
PMID- 26434781
TI - Indwelling Urinary Catheter Insertion Practices in the Emergency Department: An
Observational Study.
PMID- 26434780
TI - Economic and epidemiological impact of early antiretroviral therapy initiation in
India.
AB - INTRODUCTION: Recent WHO guidance advocates for early antiretroviral therapy
(ART) initiation at higher CD4 counts to improve survival and reduce HIV
transmission. We sought to quantify how the cost-effectiveness and
epidemiological impact of early ART strategies in India are affected by attrition
throughout the HIV care continuum. METHODS: We constructed a dynamic
compartmental model replicating HIV transmission, disease progression and health
system engagement among Indian adults. Our model of the Indian HIV epidemic
compared implementation of early ART initiation (i.e. initiation above CD4 >=350
cells/mm(3)) with delayed initiation at CD4 <=350 cells/mm(3); primary outcomes
were incident cases, deaths, quality-adjusted-life-years (QALYs) and costs over
20 years. We assessed how costs and effects of early ART initiation were impacted
by suboptimal engagement at each stage in the HIV care continuum. RESULTS:
Assuming "idealistic" engagement in HIV care, early ART initiation is highly cost
effective ($442/QALY-gained) compared to delayed initiation at CD4 <=350
cells/mm(3) and could reduce new HIV infections to <15,000 per year within 20
years. However, when accounting for realistic gaps in care, early ART initiation
loses nearly half of potential epidemiological benefits and is less cost
effective ($530/QALY-gained). We project 1,285,000 new HIV infections and 973,000
AIDS-related deaths with deferred ART initiation with current levels of care
engagement in India. Early ART initiation in this continuum resulted in 1,050,000
new HIV infections and 883,000 AIDS-related deaths, or 18% and 9% reductions
(respectively), compared to current guidelines. Strengthening HIV screening
increases benefits of earlier treatment modestly (1,001,000 new infections; 22%
reduction), while improving retention in care has a larger modulatory impact
(676,000 new infections; 47% reduction). CONCLUSIONS: Early ART initiation is
highly cost-effective in India but only has modest epidemiological benefits at
current levels of care-engagement. Improved retention in care is needed to
realize the full potential of earlier treatment.
PMID- 26434782
TI - pROC-Chemotype Plots Enhance the Interpretability of Benchmarking Results in
Structure-Based Virtual Screening.
AB - Recently, we have reported a systematic comparison of molecular preparation
protocols (using MOE or Maestro) in combination with two docking tools (GOLD or
Glide), employing our DEKOIS 2.0 benchmark sets. Herein, we demonstrate how
comparable settings of data preparation protocols can affect the profile and AUC
of pROC curves based on variations in chemotype enrichment. We show how the
recognition of different classes of chemotypes can affect the docking
performance, particularly in the early enrichment, and monitor changes in this
recognition behavior based on score normalization and rescoring strategies. For
this, we have developed "pROC-Chemotype", which is an automated protocol that
matches and visualizes ligand chemotype information together with potency classes
in the pROC profiles obtained by docking. This tool enhances the understanding of
the influence of chemotype recognition in early enrichment, but also reveals
trends of impaired recognition of chemotype classes at the end of the score
ordered rank. Identifying such issues helps to devise score-normalization
strategies to overcome this potential bias in an intuitive manner. Furthermore,
strong perturbations in chemotype ranking between different methods can help to
identify the underlying reasons (e.g., changes in the protonation/tautomerization
state). It also assists in the selection of appropriate scoring functions that
are capable to retrieve more potent and diverse hits. In summary, we demonstrate
how this new tool can be utilized to identify and highlight chemotype-specific
behavior, e.g., in dataset preparation. This can help to overcome some chemistry
related bias in virtual screening campaigns. pROC-Chemotype is made freely
available at www.dekois.com.
PMID- 26434783
TI - Comparing Counterconditioning and Extinction as Methods to Reduce Fear of
Movement-Related Pain.
AB - Cognitive-behavioral treatments for chronic pain typically target pain-related
fear; exposure in vivo is a common treatment focusing on disconfirming harm
expectancy of feared movements. Exposure therapy is tailored on Pavlovian
extinction; an alternative fear reduction technique that also alters stimulus
valence is counterconditioning. We compared both procedures to reduce pain
related fear using a voluntary joystick movement paradigm. Participants were
randomly allocated to the counterconditioning or extinction group. During fear
acquisition, moving the joystick in 2 directions (conditioned stimulus [CS+]) was
followed by a painful electrocutaneous stimulus (pain-unconditioned stimulus
[US]), whereas moving the joystick in 2 other directions was not (CS-). During
fear reduction, 1 CS+ was extinguished, but another CS+ was still followed by
pain in the extinction group; in the counterconditioning group, 1 CS+ was
extinguished and followed by a monetary reward-US, and another CS+ was followed
by both USs (pain-US and reward-US). The results indicate that
counterconditioning effectively reduces pain-related fear but that it does not
produce deeper fear reduction than extinction. Adding a reward-US to a painful
movement attenuated neither fear nor the intensity/unpleasantness of the pain.
Both procedures changed stimulus valence. We contend that changing the affective
valence of feared movements might improve fear reduction and may prevent relapse.
PERSPECTIVE: This article reports no immediate differences between
counterconditioning and extinction in reducing pain-related fear in the
laboratory. Unexpectedly, both methods also altered stimulus valence. However, we
cautiously suggest that methods explicitly focusing on altering the affective
valence of feared movements may improve the long-term effectiveness of fear
reduction and prevent relapse.
PMID- 26434784
TI - 2015 Distinguished career award: Reflections on a career in science.
AB - I was very pleased to receive the 2015 Distinguished Career Award from SSIB. This
brief manuscript contains reminisces that might stir up pleasant memories in the
older members of SSIB and also some general thoughts that I hope will be of value
to the younger investigators who are closer to the beginning of their scientific
careers. Although the organization has chosen to honor me with this special
award, my own career was shaped by a great many people who have influenced my
scientific career and I want to acknowledge them. They include Neal Miller, my
doctoral mentor at Yale; Joe Holmes and Alan Epstein, my postdoctoral mentors;
George Wolf and Reed Hainsworth, graduate student colleagues; John Brobeck, Paul
Rozin, and Phil Teitelbaum, Michael Zigmond, Joe Verbalis, Jim Smith, and Alan
Sved, faculty colleagues; Derek Denton, Paul McHugh, and James Fitzsimons,
scientific role models; John Bruno, Steve Fluharty, and Linda Rinaman, post
doctoral trainees at Pitt; and Lori Flanagan, Kath Curtis, Michael Bushey, Mike
Bykowski, Reza Manesh, Carrie Smith, Jennifer Vaughan, and Myriam Stricker,
student trainees at Pitt. I thank them all and also my colleagues in SSIB not
only for the honor of this award but for providing an abundant supply of insights
and discoveries that have stimulated me throughout my adult life, in addition to
being an attentive community in supporting my own work.
PMID- 26434785
TI - Skin temperature reveals the intensity of acute stress.
AB - Acute stress triggers peripheral vasoconstriction, causing a rapid, short-term
drop in skin temperature in homeotherms. We tested, for the first time, whether
this response has the potential to quantify stress, by exhibiting proportionality
with stressor intensity. We used established behavioural and hormonal markers:
activity level and corticosterone level, to validate a mild and more severe form
of an acute restraint stressor in hens (Gallus gallus domesticus). We then used
infrared thermography (IRT) to non-invasively collect continuous temperature
measurements following exposure to these two intensities of acute handling
stress. In the comb and wattle, two skin regions with a known thermoregulatory
role, stressor intensity predicted the extent of initial skin cooling, and also
the occurrence of a more delayed skin warming, providing two opportunities to
quantify stress. With the present, cost-effective availability of IRT technology,
this non-invasive and continuous method of stress assessment in unrestrained
animals has the potential to become common practice in pure and applied research.
PMID- 26434786
TI - Cardiovascular activity and chronic pain severity.
AB - OBJECTIVE: Objective markers of chronic pain severity are needed when examining
and treating patients with chronic pain whose suffering may be overstated or
underestimated. This study tested a hypothesis that the strength of
cardiovascular (CV) reactivity in response to a social evaluative threat and
orthostatic challenge is a reliable index of severity of pain-related complaints.
METHODS: Measurement of CV reactivity and response styles in 34 men and 16 women
with chronic pain from different bodily injuries, were retrieved from a larger
database of patients. Measurement of CV reactivity in response to a postural
challenge was repeated twice (sessions 1 and 2) on the same day of a medical
examination which includes a psychosocial evaluation . RESULTS: A decrease in
systolic blood pressure (SBP) from session 1 to session 2 was found in subjects
with low pain severity scores, but not in those with high pain severity scores.
High scores for pain catastrophizing/ magnification and pain-related emotional
distress were independently associated respectively with a SBP increase at an
early-point in time and a SBP decrease at a mid-point in time after standing up
from lying down. Stronger heart rate reactivity responses to orthostatic
challenge indicated greater protection against the presence of these chronic pain
symptoms. CONCLUSIONS: This biobehavioral protocol enables measurement of chronic
pain suffering and protection in three dimensions: physical, emotional, and
cognitive.
PMID- 26434787
TI - The influence of cancer on endocrine, immune, and behavioral stress responses.
AB - Tumors perturb various physiological systems beyond their local microenvironment,
including the immune, nervous, and metabolic systems. Given the involvement of
these systems in physiological stress responses, the goal of this review is to
compile evidence regarding whether or not cancer alters acute stress responses.
Here, we focus on stress responses that are endocrine, immune, or behavioral.
This question is clinically relevant as cancer patients are exposed to many
stressors throughout diagnosis and treatment, and then later as survivors.
Alterations in their stress responses may specifically affect how they respond to
advice, treatments, and surgery under duress. To determine whether tumors alone
alter stress responses, the relevant literature using rodent cancer models is
first reviewed. Next, the more complicated clinical literature in cancer patients
is integrated into the discussion. Based on the results of this analysis, goals
for future basic and clinical research are proposed. This work aims to advance
our understanding of the most effective methods for treating cancer patients and
supporting their long-term survival.
PMID- 26434788
TI - Invited review: Improving neonatal survival in small ruminants: science into
practice.
AB - Neonatal mortality in small ruminant livestock has remained stubbornly unchanging
over the past 40 years, and represents a significant loss of farm income,
contributes to wastage and affects animal welfare. Scientific knowledge about the
biology of neonatal adaptation after birth has been accumulating but does not
appear to have had an impact in improving survival. In this paper, we ask what
might be the reasons for the lack of impact of the scientific studies of lamb and
kid mortality, and suggest strategies to move forward. Biologically, it is clear
that achieving a good intake of colostrum, as soon as possible after birth, is
crucial for neonatal survival. This provides fuel for thermoregulation, passive
immunological protection and is involved in the development of attachment between
the ewe and lamb. The behaviour of the lamb in finding the udder and sucking
rapidly after birth is a key component in ensuring sufficient colostrum is
ingested. In experimental studies, the main risk factors for lamb mortality are
low birthweight, particularly owing to poor maternal nutrition during gestation,
birth difficulty, litter size and genetics, which can all be partly attributed to
their effect on the speed with which the lamb reaches the udder and sucks.
Similarly, on commercial farms, low birthweight and issues with sucking were
identified as important contributors to mortality. In epidemiological studies,
management factors such as providing assistance with difficult births, were found
to be more important than risk factors associated with housing. Social science
studies suggest that farmers generally have a positive attitude to improving
neonatal mortality but may differ in beliefs about how this can be achieved, with
some farmers believing they had no control over early lamb mortality.
Facilitative approaches, where farmers and advisors work together to develop
neonatal survival strategies, have been shown to be effective in achieving
management goals, such as optimising ewe nutrition, that lead to reductions in
lamb mortality. We conclude that scientific research is providing useful
information on the biology underpinning neonatal survival, such as optimal
birthweights, lamb vigour and understanding the importance of sufficient
colostrum intake, but the transfer of that knowledge would benefit from an
improved understanding of the psychology of management change on farm. Developing
tailored solutions, on the basis of adequate farm records, that make use of the
now substantial body of scientific literature on neonatal mortality will help to
achieve lower neonatal mortality.
PMID- 26434789
TI - A standardized approach to estimating survival statistics for population-based
cystic fibrosis registry cohorts.
AB - OBJECTIVES: Our objective was to quantify the effect of different statistical
techniques, inclusion/exclusion criteria, and missing data on the predicted
median survival age. STUDY DESIGN AND SETTING: Using the Canadian cystic fibrosis
registry (CCFR), the median age of survival was calculated using both the Cox
proportional hazards (PH) and the life-table methods. Through simulations, we
examined how the median age of survival would change when: (1) patients were
excluded, (2) death dates were inaccurate, (3) patients were lost to follow-up,
(4) entire years with no clinic visits were excluded even if the patient had a
visit in subsequent years, and (5) censoring patients at their date of
transplant. Simulations were run assuming 5-35% of data were affected by each
scenario. RESULTS: Over the period 2009-2013, there were 4,666 individuals in the
CCFR with 240 deaths. The observed median age of survival calculated by the Cox
PH method was 50.9 [95% confidence interval (CI): 47.4, 54.3] and 50.5 from the
life-table method (95% CI: 47.5, 53.5). Censoring patients at their transplant
date overestimated the median age of survival by 7.2 years (58.1; 95% CI: 53.3,
64.7). Simulations determined that by missing just 15% of deaths, the median age
of survival can be overestimated by 3.5 years (54.4; 95% CI: 54.2, 56.1), and
having 25% of patients lost to follow-up can underestimate the median age of
survival by 3.3 years (47.6; 95% CI: 46.8, 47.7). CONCLUSION: We present several
recommendations to assist national cystic fibrosis registries in calculating and
reporting the median age of survival in a standardized fashion. It is imperative
to state the statistical method used as well as the proportion lost to follow-up
and the treatment of missing data and transplanted patients. Registries must be
diligent in their data collection as incomplete data can lead to overestimation
and underestimation of survival.
PMID- 26434790
TI - Are not good practice statements necessarily based on evidence? Are their grades
always strong?
PMID- 26434791
TI - Klebsiella sp. FIRD 2, a TBT-resistant bacterium isolated from contaminated
surface sediment along Strait of Johor Malaysia.
AB - A possible tributyltin (TBT)-degrading bacterium isolated from contaminated
surface sediment was successfully identified as Klebsiella sp. FIRD 2. It was
found to be the best isolate capable of resisting TBT at a concentration of 1000
MUg L(-1). This was a concentration above the reported contaminated level at the
sampling station, 790 MUg L(-1). Further studies revealed that the isolate was
Gram negative and resisted TBT concentrations of up to 1500 MUg L(-1) in a
Minimal Salt Broth without the addition of any carbon source within the first 48
h of incubation. It is expected that additional work could be conducted to check
the degradation activity of this new isolate and possibly improve the degradation
capacity in order to contribute to finding a safe and sustainable remediation
solution of TBT contamination.
PMID- 26434792
TI - Differential clearance mechanisms, neutrophil extracellular trap degradation and
phagocytosis, are operative in systemic lupus erythematosus patients with
distinct autoantibody specificities.
AB - Systemic lupus erythematosus (SLE) patients are generally presented with
autoantibodies against either dsDNA or RNA-associated antigens (also known as
extractable nuclear antigens, ENA) or both. However, the mechanisms and processes
that lead to this distinctive autoantibody profile are not well understood.
Defects in clearance mechanism i.e. phagocytosis may lead to enhanced microbial
and cellular debris of immunogenic potential. In addition to defective
phagocytosis, impaired neutrophil extracellular trap (NET) degradation has been
recently reported in SLE patients. However, the extent to which both these
clearance processes (NET-degradation and phagocytosis) are operative in
serologically distinguished subsets of SLE patients is not established.
Therefore, in this report, we evaluated NET-degradation and phagocytosis
efficiency among SLE patients with different autoantibody specificities. SLE
patients were classified into three subsets based on their autoantibody profile
(anti-dsDNA, anti-ENA or both) as determined by ELISA. NET-degradation by SLE and
control sera was assessed by sytox orange-based fluorescence assay. Neutrophil
mediated phagocytosis in the presence of SLE and control sera was determined by
flowcytometry. The segregation of SLE patients revealed significant differences
in NET-degradation and phagocytosis in SLE patients with autoantibodies against
dsDNA and ENA. We report that NET-degradation efficiency was significantly
impaired in SLE patients with anti-dsDNA autoantibodies and not in those with
anti-ENA autoantibodies. In contrast to NET-degradation, neutrophil-mediated
phagocytosis was impaired in all three subsets independent of autoantibody
specificity. These observations suggest that varying clearance mechanisms are
operative in SLE subsets with anti-dsDNA or anti-ENA autoantibodies. The results
outlined in this manuscript also suggest that sub-grouping of SLE patients could
be useful in delineating the molecular and pathological processes that are often
missed when SLE patients are studied as a single group. Further, it will be
imperative to propose that therapies targeted at improving NET clearance can be
effective in anti-dsDNA(+) SLE patients.
PMID- 26434793
TI - Increasing Incidence of Thyroid Nodules and Thyroid Cancer: Does Increased
Detection of a Subclinical Reservoir Justify the Associated Anxiety and
Treatment?
AB - The incidence of thyroid cancer has been increasing over the last few decades,
and it is subject to debate regarding whether the incidence is reflective of
better diagnostic techniques and therefore better detection or if it is a
reflection of a true increase in incidence. This increase in incidence has been
most clearly manifested by an exponential increase in the diagnosis of
micropapillary thyroid carcinomas. This article reviews the diagnosis of thyroid
cancers, the dilemmas facing clinicians in the management of these micropapillary
thyroid carcinomas, and the advances in molecular diagnostics that are being used
to assist in the decision-making process. We consider the possibility of
overtreatment of a relatively indolent disease and propose a less aggressive
management plan in the appropriate clinical scenario.
PMID- 26434794
TI - Twice the negativity bias and half the positivity offset: Evaluative responses to
emotional information in depression.
AB - BACKGROUND AND OBJECTIVES: Humans have the dual capacity to assign a slightly
pleasant valence to neutral stimuli (the positivity offset) to encourage approach
behaviors, as well as to assign a higher negative valence to unpleasant images
relative to the positive valence to equally arousing and extreme pleasant images
(the negativity bias) to facilitate defensive strategies. We conducted an
experimental psychopathology study to examine the extent to which the negativity
bias and the positivity offset differ in participants with and without major
depression.. METHOD: Forty-one depressed and thirty-six healthy participants were
evaluated using a structured clinical interview for DSM-IV Axis I disorders,
questionnaires, and a computerized task designed to measure implicit affective
responses to unpleasant, neutral, and pleasant stimuli. RESULTS: The negativity
bias was significantly higher and the positivity offset was significantly lower
in depressed relative to healthy participants.. LIMITATIONS: Entry criteria
enrolling medication-free participants with minimal DSM-IV comorbidity may limit
generalizability of the findings. CONCLUSIONS: This study advances our
understanding of the positive and negative valence systems in depression,
highlighting the irregularities in the positive valence system..
PMID- 26434795
TI - Cloning and analysis of DnaJ family members in the silkworm, Bombyx mori.
AB - Heat shock proteins (Hsps) are involved in a variety of critical biological
functions, including protein folding, degradation, and translocation and
macromolecule assembly, act as molecular chaperones during periods of stress by
binding to other proteins. Using expressed sequence tag (EST) and silkworm
(Bombyx mori) transcriptome databases, we identified 27 cDNA sequences encoding
the conserved J domain, which is found in DnaJ-type Hsps. Of the 27 J domain
containing sequences, 25 were complete cDNA sequences. We divided them into three
types according to the number and presence of conserved domains. By analyzing the
gene structures, intron numbers, and conserved domains and constructing a
phylogenetic tree, we found that the DnaJ family had undergone convergent
evolution, obtaining new domains to expand the diversity of its family members.
The acquisition of the new DnaJ domains most likely occurred prior to the
evolutionary divergence of prokaryotes and eukaryotes. The expression of DnaJ
genes in the silkworm was generally higher in the fat body. The tissue
distribution of DnaJ1 proteins was detected by western blotting, demonstrating
that in the fifth-instar larvae, the DnaJ1 proteins were expressed at their
highest levels in hemocytes, followed by the fat body and head. We also found
that the DnaJ1 transcripts were likely differentially translated in different
tissues. Using immunofluorescence cytochemistry, we revealed that in the blood
cells, DnaJ1 was mainly localized in the cytoplasm.
PMID- 26434796
TI - Sequencing and characterization of the complete mitochondrial genome from the
pancreatic fluke Eurytrema pancreaticum (Trematoda: Dicrocoeliidae).
AB - The trematode Eurytrema pancreaticum is a parasite of ruminant pancreatic and
bile ducts, and also occasionally infects humans, causing eurytremiasis. In spite
of it being a common fluke of cattle and sheep in endemic regions, little is
known about the genomic resources of the parasite. We sequenced the complete
mitochondrial (mt) genome of E. pancreaticum. It is 15,031 bp in size, and
encodes 36 genes: 12 protein-coding genes, two ribosomal RNA genes, and 22
transfer RNA genes. The E. pancreaticum mt gene order is the same as that of
Dicrocoelium chinensis and Dicrocoelium dendriticum, and all genes are
transcribed in the same direction. Phylogenetic analysis based on the
concatenated amino acid sequences of 12 protein-coding genes by Bayesian
inference shows that E. pancreaticum is closely related to D. chinensis and other
members of the family Dicrocoeliidae with strong posterior probability support.
The E. pancreaticum mt genome should prove to be a useful resource for
comparative mt genomic studies of digenetic trematodes, and will provide a rich
source of DNA markers for studies into the systematics, epidemiology, and
population genetics of this parasite and other digenean trematodes.
PMID- 26434797
TI - A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in
CB6F1-non-Tg rasH2 mice.
AB - 3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods
containing hydrolyzed vegetable protein. However, limited toxicity data are
available for the risk assessment of 3-MCPD and its carcinogenic potential is
controversial. To evaluate the potential toxicity and determine the dose levels
for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered
once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight
(b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males
and females per dose). The standard toxicological evaluations were conducted
during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3
males and 1 female died during the study and showed clinical signs such as thin
appearance and subdued behavior accompanied by significant decreases in mean b.w.
Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative
germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in
the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the
100, >=25, >=50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion,
3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart.
The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was <=25 and 25 mg/kg
b.w./day in males and females, respectively.
PMID- 26434798
TI - The Brain Protective Effect of rTMS (Repetitive Transcranial Magnetic
Stimulation) in Depression: A Mini-Review in Animal Studies.
AB - There are rapidly replicating human data suggesting the therapeutic and
neurorestorative role of repetitive transcranial magnetic stimulation (rTMS) in
clinical depression. However there are only limited experimental studies in the
literature and the neurobiological mechanisms of the technique are still unclear.
Studies have suggested that modulating of either excitatory or inhibitory neural
circuitry may be responsible for the mechanism of action of rTMS while it is
still unclear whether rTMS exerts a neuroprotective effect. In the light of these
findings, we aimed to review the neuroprotective effect of rTMS in animal models
of depression. We have shown that rTMS may exert significant neuroprotective
effect through acting on the oxidative injury, stress hormones, dopamine and
serotonin levels, Brain Derived Neurotrophic Factor expression, neuroinflamation
and hippocampal cell proliferation.
PMID- 26434799
TI - Robust Modeling and Scaffold Hopping: Case Study Based on HIV Reverse
Transcriptase Inhibitors Type-1 Data.
AB - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) is the causative agent of
AIDS occurs across mucosal surfaces or by direct inoculation. OBJECTIVE: The
objective of this study was to consider chemically diverse scaffold sets of HIV-1
Reverse Transcriptase Inhibitors (HIV-1 RTI) subjected to ideal oriented QSAR
with large descriptor space. METHOD: We generated a four-parameter QSAR model
based on 111 data points, which provided an optimum prediction of HIV-1 RTI for
overall 367 experimentally measured compounds. RESULTS: The robustness of the
model is demonstrated by its statistical validation (Ntraining = 111, R2 = 0.85,
Q2lmo = 0.84) and by the prediction of HIV-1 inhibition activity for
experimentally measured compounds. CONCLUSION: Finally, 5 novel hit compounds
were designed in silico by using a virtual screening approach. The new hits met
all the pharmacophore constraints and predicted pIC50 values within the binding
ability of HIV-1 RT protein targets.
PMID- 26434800
TI - Identification of Bostrycin Derivatives as Potential Inhibitors of Mycobacterium
tuberculosis Protein Tyrosine Phosphatase (MptpB).
AB - BACKGROUND: As a virulence factor secreted into host cells, the Mycobacterium
tuberculosis protein tyrosine phosphatase (MptpB) mediates the intracellular
survival of M. tuberculosis. MptpB has become an attractive target for the
development of new anti-tuberculosis drugs. OBJECTIVE: In the present study, we
assessed the inhibitory activity of marine fungus-derived bostrycin and its
derivatives against MptpB in vitro. METHOD: The compounds were tested for their
inhibitory effects on MptpB in vitro and the inhibition mode. The binding
characteristics of inhibitors and MptpB were determined by microscale
thermophoresis (MST). RESULTS: Our data showed that one of the derivatives,
compound 25 (IC50 = 64.6 +/- 9.1 uM), possessed a greater inhibitory activity
compared with bostrycin (IC50 = 327.6 +/- 60.4 uM) and behaved as a non
competitive inhibitor. The binding characteristic of MptpB and compound 25 was
determined by MST, exhibiting a moderate affinity with a KD constant of 5200 +/-
1020 nM. CONCLUSION: We, for the first time, reported that bostrycin and one of
its analogues exhibited inhibitory activity against MptpB, which possessed
potential as novel agents against tuberculosis.
PMID- 26434801
TI - Cytotoxic Effects of Salvinorin A, A Major Constituent of Salvia divinorum.
AB - S. divinorum is a psychoactive plant that has been consumed as a recreational
drug of abuse in the last years. Salvinorin A is its main constituent, and is
responsible for the observed psychoactive effects. Both S. divinorum and
salvinorin A have become controlled drugs in several countries, but they are not
listed in the Schedules of the United Nations Drug Conventions. Regarding the
effects of S. divinorum consumption, almost all studies are based on in vivo or
on surveys, and there are no studies in vitro on its toxicity. Furthermore, all
studies are focused on the acute toxicological effects of the plant. So, it is of
utmost importance to further investigate the effects of S. divinorum and
salvinorin A, particularly using in vitro models, after prolonged exposures. In
this context, the present work evaluated the in vitro toxicity induced by S.
divinorum or salvinorin A in six cell lines, through MTT assays and LC50
determination. Overall, results showed that both S. divinorum and salvinorin A
are cytotoxic, dose- and time-dependent. Also, Hep G2 and Caco 2 (to a lesser
extent) cells showed lower sensitivity to S. divinorum and salvinorin A when
compared to the other studied cell lines. To our knowledge, this is the first
work focused on the in vitro toxicity of S. divinorum and salvinorin A using a
variety of cell lines, which are extensively described in literature and have
been widely used in several in vitro studies.
PMID- 26434802
TI - Disrupted prefrontal activity during emotion processing in complicated grief: An
fMRI investigation.
AB - Complicated Grief, marked by a persistent and intrusive grief lasting beyond the
expected period of adaptation, is associated with a relative inability to
disengage from idiographic loss-relevant stimuli (O'Connor and Arizmendi, 2014).
In other populations, functional magnetic resonance imaging (fMRI) studies
investigating the neural networks associated with this bias consistently
implicate the anterior cingulate cortex (ACC) during emotion regulation. In the
present study, twenty-eight older adults were categorized into three groups based
on grief severity: Complicated Grief (n=8), Non-Complicated Grief (n=9), and
Nonbereaved, married controls (n=11). Using a block design, all participants
completed 8 blocks (20 stimuli per block) of the ecStroop task during fMRI data
acquisition. Differences in neural activity during grief-related (as opposed to
neutral) stimuli across groups were examined. Those with Complicated Grief showed
an absence of increased rostral ACC (rACC) and fronto-cortical recruitment
relative to Nonbereaved controls. Activity in the orbitofrontal cortex (x=6,
y=54, z=-10) was significantly elevated in the Non-Complicated Grief group when
compared to Nonbereaved controls. Post hoc analysis evidenced activity in the
dorsal ACC in the Complicated Grief and Nonbereaved groups late in the task.
These findings, supported by behavioral data, suggest a relative inability to
recruit the regions necessary for successful completion of this emotional task in
those with Complicated Grief. This deficit was not observed in recruitment of the
orbitofrontal cortex and the rACC during processing of idiographic semantic
stimuli in Non-Complicated Grief.
PMID- 26434804
TI - Obesity and reproduction: a committee opinion.
AB - The purpose of this ASRM Practice Committee report is to provide clinicians with
principles and strategies for the evaluation and treatment of couples with
infertility associated with obesity. This revised document replaces the Practice
Committee document titled, "Obesity and reproduction: an educational bulletin,"
last published in 2008 (Fertil Steril 2008;90:S21-9).
PMID- 26434803
TI - Adolescent neurodevelopment of cognitive control and risk-taking in negative
family contexts.
AB - Adolescents have an increased need to regulate their behavior as they gain access
to opportunities for risky behavior; however, cognitive control systems necessary
for this regulation remain relatively immature. Parents can impact their
adolescent child's abilities to regulate their behavior and engagement in risk
taking. Since adolescents undergo significant neural change, negative parent
child relationship quality may impede or alter development in prefrontal regions
subserving cognitive control. To test this hypothesis, 20 adolescents completed a
Go/NoGo task during two fMRI scans occurring 1year apart. Adolescents reporting
greater family conflict and lower family cohesion showed longitudinal increases
in risk-taking behavior, which was mediated by longitudinal increases in left
VLPFC activation during cognitive control. These results underscore the
importance of parent-child relationships during early adolescence, and the neural
processes by which cognitive control may be derailed and may lead to increased
risk taking.
PMID- 26434805
TI - Transitioning through AIDS epidemics - gender and temporality.
AB - OBJECTIVE: To understand the evolution of AIDS over time in Mato Grosso do Sul,
Brazil, using incidence, lethality, and mortality coefficients. METHODS: A
descriptive epidemiological study based on time series analysis of secondary data
from the Notifiable Diseases Information System reported between 1985 and 2012.
RESULTS: The prevalence of AIDS was higher among men, with evidence of
feminization during the first 14 years of the epidemic. There was no
statistically significant sex difference in AIDS lethality. Women were 1.3 times
more likely to survive than men. CONCLUSIONS: Gender differences must be
considered when designing new HIV/AIDS prevention strategies.
PMID- 26434808
TI - Synthetic multivalency for biological applications.
AB - Current directions and emerging possibilities under investigation for the
integration of synthetic and semi-synthetic multivalent architectures with
biology are discussed. Attention is focussed around multivalent interactions,
their fundamental role in biology, and current and potential approaches in
emulating them in terms of structure and functionality using synthetic
architectures.
PMID- 26434807
TI - Passive dust collectors for assessing airborne microbial material.
AB - BACKGROUND: Settled airborne dust is used as a surrogate for airborne exposure in
studies that explore indoor microbes. In order to determine whether detecting
differences in dust environments would depend on the sampler type, we compared
different passive, settled dust sampling approaches with respect to displaying
qualitative and quantitative aspects of the bacterial and fungal indoor
microbiota. RESULTS: Settled dust sampling approaches-utilizing plastic petri
dishes, TefTex material, and electrostatic dustfall collectors (EDCs)-were
evaluated in indoor spaces in the USA and Finland and in an experimental chamber
study. The microbial content was analyzed with quantitative PCR (qPCR) to
quantify total bacterial and fungal biomass and through high-throughput
sequencing to examine bacterial community composition. Bacterial composition and
diversity were similar within a sampling environment regardless of the sampler
type. The sampling environment was the single largest predictor of microbial
community composition within a study, while sampler type was found to have much
less predictive power. Quantitative analyses in indoor spaces indicated highest
yields using a petri dish approach, followed by sampling with EDCs and TefTex.
The highest correlations between duplicate samples were observed for EDC and
petri dish approaches, indicating greater experimental repeatability for these
sampler types. For the EDC samples, it became apparent that, due to the fibrous
nature of the material, a rigorous extraction protocol is crucial to obtain
optimal yields and stable, repeatable results. CONCLUSIONS: Correlations between
sampler types were strong both in compositional and quantitative terms, and thus,
the particular choice of passive settled dust sampler is not likely to strongly
alter the overall conclusion of a study that aims to characterize dust across
different environments. Microbial cell abundances determined from settled dust
varied with the use of different sampling approaches, and thus, consistency in
the method is necessary to allow for absolute comparisons within and among
studies. Considering practical aspects, petri dishes were found to be an
inexpensive, simple, and feasible approach that showed the highest quantitative
determinations under typical building conditions, though the choice of sampler
will ultimately depend on study logistics and characteristics such as low- or
high-exposure settings.
PMID- 26434806
TI - The Regulatory Domain of Squalene Monooxygenase Contains a Re-entrant Loop and
Senses Cholesterol via a Conformational Change.
AB - Squalene monooxygenase (SM) is an important control point in cholesterol
synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase. Although it is known
to associate with the endoplasmic reticulum, its topology has not been
determined. We have elucidated the membrane topology of the sterol-responsive
domain of SM comprising the first 100 amino acids fused to GFP (SM N100-GFP) by
determining the accessibility of 16 introduced cysteines to the cysteine
reactive, membrane-impermeable reagent PEG-maleimide. We have identified a region
integrally associated with the endoplasmic reticulum membrane that is likely to
interact with cholesterol or respond to cholesterol-induced membrane effects. By
comparing cysteine accessibility with and without cholesterol treatment, we
further present evidence to suggest that cholesterol induces a conformational
change in SM N100-GFP. This change is likely to lead to its targeted degradation
by the ubiquitin-proteasome system because degradation is blunted by treatment
with the chemical chaperone glycerol, which retains SM N100-GFP in its native
conformation. Furthermore, degradation can be disrupted by insertion of two N
terminal myc tags, implicating the N terminus in this process. Together, this
information provides new molecular insights into the regulation of this critical
control point in cholesterol synthesis.
PMID- 26434809
TI - [Advanced heart failure due to endomyocardial fibroelastosis].
PMID- 26434810
TI - A systematic review of the clinical validity of the CologuardTM genetic test for
screening colorectal cancer.
AB - OBJECTIVES: The aim of this study was to assess the available evidence on the
validity, diagnostic accuracy and clinical utility of the multitarget DNA test in
faeces (CologuardTM) for screening for colorectal cancer (CRC). MATERIAL AND
METHODS: A systematic review was performed by consulting MedLine, EMBASE and Web
of Science to July 2014. Studies on diagnostic tests were selected that evaluated
the test in asymptomatic adults who underwent CRC screening. The quality and risk
of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies
tool. The level of evidence was defined according to the National Institute for
Health and Clinical Excellence. A qualitative synthesis was conducted. RESULTS: A
total of 299 literature references were identified, including 1 synthesis report
and 5 diagnostic test studies. Three of the 5 studies had a case-control design
in Sackett phase II and were of moderate quality, and 2 had a prospective design
in Sacket phase III and were of high quality. The sensitivity for detecting CRC
was greater than 90%, but only 40% for detecting advanced adenomas. The test
provided conclusive diagnostic evidence to rule out CRC (negative likelihood
ratio, LR-: 0.02-0.09), although it was not useful for ruling out advanced
adenoma (LR-: 0.5-0.7). CONCLUSIONS: The CologuardTM test is a valid screening
test for ruling out cancerous lesions but is suboptimal for ruling out
precancerous lesions. There is no evidence in terms of mortality, survival or
cost-effectiveness.
PMID- 26434811
TI - Clinical practice guidelines for posmenopausal, glucocorticoid-induced and male
osteoporosis. Spanish Society for Research on Bone and Mineral Metabolism (3rd
updated version 2014).
AB - These guidelines update issues covered in previous versions and introduce new
ones that have arisen in recent years. The former refer mainly to the therapeutic
developments that have been made during this time (zoledronate, denosumab,
bazedoxifene), which have led to a change in the drug selection algorithm. The
latter deal with therapeutic management, the description of new adverse effects
(which have led to changes in therapeutic behaviour patterns, as is the case with
atypical fracture of the femur), treatment duration (with consideration for the
so-called "therapeutic holidays"), the so-called sequential treatment and changes
in treatment imposed by certain circumstances. A new algorithm has been
introduced for sequential treatment. Attention has also been paid to
vertebroplasty and kyphoplasty.
PMID- 26434813
TI - Investigation of Fickian diffusion in the ternary mixtures of water-ethanol
triethylene glycol and its binary pairs.
AB - We present a comprehensive experimental study of isothermal Fickian diffusion in
the ternary and binary liquid mixtures of water, ethanol, and triethylene glycol
over the entire ternary composition space. 21 ternary mixtures inside the
composition triangle have been investigated by means of the Taylor dispersion
technique and 30 binary mixtures by Taylor dispersion and/or optical beam
deflection in a Soret cell. The scalar binary diffusion coefficient has been
determined along all three binary boundaries of the composition space and
compared with estimations based on the Stokes-Einstein relation using stick or
slip boundary conditions. The four elements of the ternary diffusion matrix and
the diffusion eigenvalues were determined over a large portion of the composition
triangle. The pseudo-binary diffusion coefficients obtained in Taylor dispersion
experiments with either one of the two independent concentrations kept constant
are comparable to the two diffusion eigenvalues. One of the two off-diagonal
elements of the diffusion matrix is of the same order as the diagonal ones and,
hence, not negligible, whereas the other one is approximately one order of
magnitude smaller. Where available, our results compare well with literature
data. The investigated compositions also comprise the five compositions that are
scheduled for microgravity experiments in the ESA DCMIX3 project.
PMID- 26434812
TI - Detecting compartmental non-Gaussian diffusion with symmetrized double-PFG MRI.
AB - Diffusion in tissue and porous media is known to be non-Gaussian and has been
used for clinical indications of stroke and other tissue pathologies. However,
when conventional NMR techniques are applied to biological tissues and other
heterogeneous materials, the presence of multiple compartments (pores) with
different Gaussian diffusivities will also contribute to the measurement of non
Gaussian behavior. Here we present symmetrized double PFG (sd-PFG), which can
separate these two contributions to non-Gaussian signal decay as having distinct
angular modulation frequencies. In contrast to prior angular d-PFG methods, sd
PFG can unambiguously extract kurtosis as an oscillation from samples with
isotropic or uniformly oriented anisotropic pores, and can generally extract a
combination of compartmental anisotropy and kurtosis. The method further fixes
its sensitivity with respect to the time dependence of the apparent diffusion
coefficient. We experimentally demonstrate the measurement of the fourth cumulant
(kurtosis) of diffusion and find it consistent with theoretical predictions. By
enabling the unambiguous identification of contributions of compartmental
kurtosis to the signal, sd-PFG has the potential to help identify the underlying
micro-structural changes corresponding to current kurtosis based diagnostics, and
act as a novel source of contrast to better resolve tissue micro-structure.
PMID- 26434814
TI - Comparative Efficacy of Four Imaging Instruments for Breast Cancer Screening.
AB - Sensitivity and specificity are the two most important indicators in selection of
medical imaging devices for cancer screening. Breast images taken by conventional
or digital mammography, ultrasound, MRI and optical mammography were collected
from 2,143,852 patients. They were then studied and compared for sensitivity and
specificity results. Optical mammography had the highest sensitivity (p<0.001 and
p<0.006) except with MRI. Digital mammography had the highest specificity for
breast cancer imaging. A comparison of specificity between digital mammography
and optical mammography was significant (p<0.021). If two or more breast
diagnostic imaging tests are requested the overall sensitivity and specificity
will increase. In this literature review study patients at high-risk of breast
cancer were studied beside normal or sensitive women. The image modality
performance of each breast test was compared for each.
PMID- 26434815
TI - Survivin as a Potential Target for Cancer Therapy.
AB - In 1997 for the first time, survivin was described by Amborsini et al. as an anti
apoptotic protein. Subsequent studies revealed that survivin is a multifunctional
protein that plays critical roles in several crucial cell processes such as
apoptosis, cell cycle, chromosome movement, mitosis and cellular stress
responses. Moreover, it's over- expression in cancer cells versus normal cells is
associated with chemotherapy resistance, increased tumor recurrence, and shorter
patient survival. All of these features make survivin a promising target for
cancer therapy. Here, we review the potential characteristics of survivin as a
tumor marker.
PMID- 26434816
TI - Roles of Human Papillomaviruses and p16 in Oral Cancer.
AB - Head and neck cancer, including oral cancer, is the sixth most common cancer in
humans worldwide. More than 90% of oral cancers are of squamous cell carcinoma
type. Recent studies have shown a strong relationship between human
papillomavirus (HPV) infection and head and neck cancer, especially oropharyngeal
squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC).
Moreover, the incidence of HPV-related OSCC appears to be on the rise while HPV
unrelated OSCC tends to have stabilized in the past decades. p16, a tumor
suppressor gene, normally functions as a regulator of the cell cycle. Upon
infection with high-risk types of HPV (HR-HPV), particularly types 16, 18, 31,
33, 34, 35, 39, 51, 52, 56, 58, 59, 66, 68, and 70, the expression of p16 is
aberrantly overexpressed. Therefore, the expression of p16 is widely used as a
surrogate marker for HPV infection in head and neck cancer.
PMID- 26434817
TI - Roles of Signaling Pathways in the Epithelial-Mesenchymal Transition in Cancer.
AB - The epithelial-mesenchymal transition (EMT) is a cellular process though which an
epithelial phenotype can be converted into a phenotype of mesenchymal cells.
Under physiological conditions EMT is important for embryogenesis, organ
development, wound repair and tissue remodeling. However, EMT may also be
activated under pathologic conditions, especially in carcinogenesis and
metastatic progression. Major signaling pathways involved in EMT include
transforming growth factor beta(TGF-beta), Wnt, Notch, Hedgehog and other
signaling pathways. These pathways are related to several transcription factors,
including Twist, Smads and zinc finger proteins snail and slug. These interact
with each other to provide crosstalk between the relevant signaling pathways.
This review lays emphasis on studying the relationship between EMT and signaling
pathways in carcinogenesis and metastatic progression.
PMID- 26434818
TI - Prevention of Chemotherapy-Induced Nausea and Vomiting in Cancer Patients.
AB - The supportive care of patients receiving antineoplastic treatment has
dramatically improved over the past few years and development of effective
measures to prevent nausea and vomiting after chemotherapy serves as one of the
most important examples of this progress. A patient who starts cancer treatment
with chemotherapy lists chemotherapy-induced nausea and vomiting as among their
greatest fears. Inadequately controlled emesis impairs functional activity and
quality of life, increases the use of health care resources, and may occasionally
compromise adherence to treatment. New insights into the pathophysiology of
chemotherapy-induced nausea and vomiting, a better understanding of the risk
factors for these effects, and the availability of new antiemetic agents have all
contributed to substantial improvements in emetic control. This review focuses on
current understanding of chemotherapy-induced nausea and vomiting and the status
of pharmacological interventions for their prevention and treatment.
PMID- 26434819
TI - Tumor-Suppression Mechanisms of Protein Tyrosine Phosphatase O and Clinical
Applications.
AB - Tyrosine phosphorylation plays an important role in regulating human
physiological and pathological processes. Functional stabilization of tyrosine
phosphorylation largely contributes to the balanced, coordinated regulation of
protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs).
Research has revealed PTPs play an important suppressive role in carcinogenesis
and progression by reversing oncoprotein functions. Receptor-type protein
tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been
identified to have some roles in tumor development. Some reports have shown PTPRO
over-expression in tumors can not only inhibit the frequency of tumor cell
division and induce tumor cell death, but also suppress migration. However, the
tumor-suppression mechanisms are very complex and understanding is incomplete,
which in some degree blocks the further development of PTPRO. Hence, in order to
resolve this problem, we here have summarized research findings to draw
meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be
diverse, such as controlling G0/G1 of the tumor cell proliferation cycle,
inhibiting substrate phosphorylation, down-regulating transcription activators
and other activities. In clinical anticancer efforts, expression level of PTPRO
in tumors can not only serve as a biomarker to monitor the prognosis of patients,
but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re
activation of PTPRO in tumor tissues, not only can induce tumor volume reduction,
but also enhance the susceptibility to chemotherapy drugs. So, we can propose
that these research findings of PTPRO will not only support new study ideas and
directions for other tumor- suppressors, importantly, but also supply a
theoretical basis for researching new molecular targeting agents in the future.
PMID- 26434820
TI - Effects of Two Traditional Chinese Cooking Oils, Canola and Pork, on pH and
Cholic Acid Content of Faeces and Colon Tumorigenesis in Kunming Mice.
AB - Faecal pH and cholate are two important factors that can affect colon
tumorigenesis, and can be modified by diet. In this study, the effects of two
Chinese traditional cooking oils (pork oil and canola/rapeseed oil) on the pH and
the cholic acid content in feces, in addition to colon tumorigenesis, were
studied in mice. Kunming mice were randomized into various groups; negative
control group (NCG), azoxymethane control group (ACG), pork oil group (POG), and
canola oil Ggroup (COG). Mice in the ACG were fed a basic rodent chow; mice in
POG and COG were given 10% cooking oil rodent chow with the respective oil type.
All mice were given four weekly AOM (azoxymethane) i.p. injections (10 mg/kg).
The pH and cholic acid of the feces were examined every two weeks. Colon tumors,
aberrant crypt foci and organ weights were examined 32 weeks following the final
AOM injection. The results showed that canola oil significantly decreased faecal
pH in female mice (P<0.05), but had no influence on feces pH in male mice
(P>0.05). Pork oil significantly increased the feces pH in both male and female
mice (P<0.05). No significant change was found in feces cholic acid content when
mice were fed 10% pork oil or canola oil compared with the ACG. Although Kunming
mice were not susceptible to AOM-induced tumorigenesis in terms of colon tumor
incidence, pork oil significantly increased the ACF number in male mice. Canola
oil showed no influence on ACF in either male or female mice. Our results
indicate that cooking oil effects faecal pH, but does not affect the faecal
cholic acid content and thus AOM-induced colon neoplastic ACF is modified by
dietary fat.
PMID- 26434821
TI - Knowledge of Female Undergraduate Students on Breast Cancer and Breast Self
examination in Klang Valley, Malaysia.
AB - BACKGROUND: In Malaysia, breast cancer is the first cancer among females
regardness of race. AIM: The purpose of this study was to identify the knowledge
and BSE practice among undergraduate female students at four public universities
in Klang Valley, Malaysia. MATERIALS AND METHODS: This cross-sectional study was
conducted among 820 undergraduate female students using a self-administered
questionnaire covering socio-demographic data, knowledge of breast cancer and BSE
practice. RESULTS: The mean age of the respondents was 21.7+/-1.2 years. The
majority of them were single (96.8%), Malay (91.9%) and 16.5% of respondents had
a family history of breast cancer. This study showed low level of knowledge on
breast cancer and breast self-examination among participants. Only 19.6%
participants were performing BSE regularly. Knowledge of breast self-examination
was significantly associated with BSE practice (p=0.00). Also, there were
significant associations between performing BSE with age, marital status and
being trained by a doctor for doing BSE (p<0.05). CONCLUSIONS: Our findings
showed that the rate of BSE practice and knowledge of breast cancer is inadequate
among young Malaysian females. A public health education program is essential to
improve breast cancer prevention among this group.
PMID- 26434822
TI - An Empirical Study on Traditional, Complementary and Alternative Medicine Usage
among Malaysian Cancer Patients.
AB - Usage of traditional, complementary and alternative medicine (TCAM) has gained
popularity over the past few years. However, very little is known about TCAM use
among Malaysian cancer patients. This study aimed to identify the determinants of
TCAM usage among cancer patients with determination of relationships between
demographic factors, patient satisfaction with conventional treatment, knowledge
on TCAM and healthcare professional influence. Patient's perceptions towards TCAM
were also determined. A simple random convenient sampling method was used to
recruit 354 patients from Hospital Kuala Lumpur between February to April 2013.
All were directly interviewed with a structured questionnaire. In this study, 172
respondents were TCAM users. There was no significant differences between
demographic background of respondents in the usage of TCAM. Minimal correlation
was found between patient satisfaction with the conventional treatment and usage
of TCAM (r=0.091). A poor correlation was found between healthcare professional's
influence and TCAM usage (r=-0.213) but the results suggested that increase in
influence would decrease TCAM usage. Patient TCAM knowledge correlated negatively
with the TCAM usage (r=-0.555) indicated that cancer patients are less likely to
use TCAM when they have more TCAM knowledge. Healthcare professionals should be
fully equipped with the necessary TCAM knowledge while maintaining patient
satisfaction with the conventional treatment. They should also intervene on
patient TCAM usage where a potential drug interaction or a harmful adverse event
can occur.
PMID- 26434823
TI - Risk Factors for Thyroid Cancer in Females Using a Logit Model in Lahore,
Pakistan.
AB - BACKGROUND: Thyroid cancer (TC) is a more common endocrine malignancy in females
and is a major cause of death in developing countries. Therefore the aim of this
study was to explore possible risk factors of thyroid cancer in females of
Pakistan. MATERIALS AND METHODS: This study covered 232 females, including 127
(54.7%) cases and 105 (45.2%) controls, from the INMOL Hospital and Sheikh Zayed
Hospital, Lahore. Different risk factors were explored by the descriptive and
inferentially statistics. Odds ratios and 95% confidence intervals for different
risk factors were computed using logistic regression. RESULTS: The results showed
six risk factors, marital status, family history of thyroid cancer, iodine in the
diet, oxidative stress, fast food and fried food, to demonstrate positive
significant links to thyroid cancer (odds ratios and 95% confidence intervals of
:2.152, 1.104-4.198; 2.630, 1.416-4.887; 2.391, 1.282-4.458; 4.115, 2.185-7.750;
3.656, 1.851-7.223; 2.357, 1.268-4.382; and 2.360, 1.199-4.643, respectively).
CONCLUSIONS: The Oxidative stress, marital status, family history of cancer, fast
food, use of iodine diet and fried food are the risk factors of thyroid cancer in
females.
PMID- 26434824
TI - Breast Cancer Awareness among Middle Class Urban Women--a Community-Based Study
from Mumbai, India.
AB - Targeting breast cancer awareness along with comprehensive cancer care is
appropriate in low and middle income countries like India, where there are no
organized and affordable screening services. It is essential to identify the
existing awareness about breast cancer in the community prior to launching an
organized effort. This study assessed the existing awareness about breast cancer
amongst women and their health seeking practices in an urban community in Mumbai,
India. A postal survey was undertaken with low or no cost options for returning
the completed questionnaires. The majority of the women were aware about cancer
but awareness about symptoms and signs was poor. Women were willing to accept
more information about cancer and those with higher awareness scores were more
likely to seek medical help. They were also more likely to have undergone breast
examination in the past and less likely to use alternative medicines. High income
was associated with better awareness but this did not translate into better
health seeking behaviour. Organized programmes giving detailed information about
breast cancer and its symptoms are needed and women from all income categories
need to be encouraged for positive change towards health seeking. Further
detailed studies regarding barriers to health seeking in India are necessary.
PMID- 26434825
TI - Model Based on Alkaline Phosphatase and Gamma-Glutamyltransferase for Gallbladder
Cancer Prognosis.
AB - PURPOSE: To evaluate the prognostic value of alkaline phosphatase (ALP) and gamma
glutamyltransferase (GGT) in gallbladder cancer (GBC). MATERIALS AND METHODS:
Serum ALP and GGT levels and clinicopathological parameters were retrospectively
evaluated in 199 GBC patients. Receiver operating characteristic (ROC) curve
analysis was performed to determine the cut-off values of ALP and GGT. Then,
associations with overall survival were assessed by multivariate analysis. Based
on the significant factors, a prognostic score model was established. RESULTS: By
ROC curve analysis, ALP>=210 U/L and GGT>=43 U/L were considered elevated.
Overall survival for patients with elevated ALP and GGT was significantly worse
than for patients within the normal range. Multivariate analysis showed that the
elevated ALP, GGT and tumor stage were independent prognostic factors. Giving
each positive factor a score of 1, we established a preoperative prognostic score
model. Varied outcomes would be significantly distinguished by the different
score groups. By further ROC curve analysis, the simple score showed great
superiority compared with the widely used TNM staging, each of the ALP or GGT
alone, or traditional tumor markers such as CEA, AFP, CA125 and CA199.
CONCLUSIONS: Elevated ALP and GGT levels were risk predictors in GBC patients.
Our prognostic model provides infomration on varied outcomes of patients from
different score groups.
PMID- 26434826
TI - Clinicopathology Profile and Bone Involvement of Multiple Myeloma Patients in
Dharmais National Cancer Hospital, Indonesia.
AB - BACKGROUND: Even though rarely found in Indonesia, the incidence of multiple
myeloma (MM) is increasing every year. Bone involvement of MM is the most often a
clinical disorder which leads to worsening clinical conditions and low quality of
life of patients. PURPOSE: To determine the clinicopathology profile of bone
involvement of MM patients in Indonesia. MATERIALS AND METHODS: The cross
sectional study of MM conducted at Dharmais National Cancer Hospital (DNCH) by
collecting data from medical records of MM patients who came to DNCH in period
2008-2012. RESULTS: There were 39 MM patients all with age above 60 years. There
were 56.4% male and 43.6% female patients. Most were diagnosed at stage III
(32.4%), and 41% had obesity. The comorbid conditions were anemia (82.9%),
hypoalbuminemia (60%), increased creatinine level (38.5%), increased beta2
microglobulin level (94.1%), increased LDH level (23.1%) and plasmocytes above
30% (65%), but only 4.2% patients presented with hypercalcemia. Meanwhile, bone
involvement occurred in 76.9% of MM patients with 4 lesions on average and a
maximum of 16 lesions. The locations of bone lesions were spine (70%), skull
(70%), pelvis (33.3%), humerus (30%), and femur (30%). CONCLUSIONS: The incidence
of MM in Indonesia is increasing annually with bone involvement in more than
three-fourths, but interestingly without hypercalcemia.
PMID- 26434827
TI - Head and neck extra nodal NHL (HNENL)--Treatment Outcome and Pattern of failure-
A Single Institution Experience.
AB - BACKGROUND: Extra nodal lymphoma (ENL) constitutes about 33 % of all non
Hodgkin's lymphoma. 18-28% develops in the head and neck region. A multimodality
treatment with multi-agent chemotherapy (CT) and radiotherapy (RT) is considered
optimum. MATERIALS AND METHODS: We retrieved the treatment charts of patients of
HNENL treated in our institute from 2001-2012. The charts were reviewed and the
demographic, treatment details and outcome of HNENL patients were retrieved using
predesigned pro-forma. RESULTS: We retrieved data of 75 consecutive patients
HNENL. Median age was 47 years (Range: 8-76 years). Of the 75 patients 51 were
male and 24 were female. 55 patients were evaluable. The patient and tumor
characteristics are summarized in Table 1. All patients were staged
comprehensively with contrast enhanced computed tomography of head, neck, thorax,
abdomen, pelvis and bone marrow aspiration and biopsy 66 patients received a
combination multi-agent CT with CHOP being the commonest regimen. 42 patients
received 4 or lesser number of cycles of chemotherapy whereas 24 received more
than 4 cycles chemotherapy. Post radiotherapy, 41 out of 42 patients had a
complete response at 3 months. Only 21 patients had a complete response after
chemotherapy. All patients received radiation (mostly involved field radiation)
as a part of the treatment. The median radiation dose was 45 Gray (Range: 36 Gray
50 Gray). The radiation was planned by 2D fluoro simulation based technique in 37
cases and by 3 Dimensional conformal radiation therapy (3DCRT) in 36 cases. Two
patients were planned by the intensity modulated radiation therapy (IMRT)
technique. IMRT was planned for one thyroid and one nasal cavity primary. 5
patients experienced relapse after a median follow up of 19 months. The median
survival was not reached. The estimated two and three year survival were 92.9%
(95%CI-68.6-95.35) and 88% (95%CI-60.82-92.66) respectively. Univariate analysis
revealed higher stage and poorer baseline performance status to be significantly
associated with worse progression free survival. 5 patients progressed (relapse
or primary disease progression) after treatment. Of the 5 patients, two patients
were primary orbital NHL, two patients had NHL nasal cavity and one was NHL
thyroid. CONCLUSIONS: Combined modality treatment in HNENL confers excellent
disease control with acceptable side effects.
PMID- 26434828
TI - Relationships between Body Image, Body Mass Index, and Smoking in Korean
Adolescents: Results of a Nationwide Korea Youth Risk Behavior Web-based Survey.
AB - OBJECTIVE: This study assessed the association between subjective body image or
objective body mass index (BMI) and the risk of daily smoking in Korean
adolescents, with a purpose of identifying the most suitable models. MATERIALS
AND METHODS: Using the 2013 9th Korea Youth Risk Behavior Web-based Survey data
for 72,435 students, odds ratios were calculated for daily smoking in the past
month, according to the subjective body image and calculated BMI using a
respective multiple logistic regression model. The combined effect of these two
factors was also analyzed by pairing a BMI category with a subjective body image
category, using odds ratios for the same event within each sex group. RESULTS:
Among the surveyed students, 7.2% of boys and 1.8% of girls were classified as
daily smokers. Students who perceived themselves as being very obese tended to be
at lower risk of daily smoking (OR=0.61 in boys with 95% CI=0.47 to 0.79; OR=0.66
in women with 95% CI=0.47 to 0.93). In addition, boys within the obese or
overweight BMI category showed a lower risk of daily smoking (OR=0.86, 95% CI:
0.77-0.96). Lean BMI was significantly associated with higher odds ratios for
daily smoking only in female students (OR=1.24, 95% CI: 1.02-1.52). When pairing
these two objective and subjective factors, results suggested that subjective
body image has a greater effect on daily smoking than BMI in both boys and girls.
CONCLUSIONS: In both male and female students, subjective body image had a
greater effect on daily smoking than body mass index. A model using the
combination of BMI and subjective body image was the best fit in girls, in
contrast to the model using subjective body image only best suitable in boys, for
the prediction of daily smoking. These results including several factors
associated with daily smoking in Korean students, provide useful data for the
development and implementation of smoking intervention and cessation programs for
adolescents.
PMID- 26434829
TI - Anticancer Activity of Atractylodes lancea (Thunb.) DC in a Hamster Model and
Application of PET-CT for Early Detection and Monitoring Progression of
Cholangiocarcinoma.
AB - Opisthorchis viverrini (OV)-induced cholangiocarcinoma (CCA) is an important
cancer in the Great Mekong region, particularly in Thailand. Limitations of
treatment options and the lack of an effective diagnostic tool for early
detection of CCA are major concerns for the control of this type of cancer. The
aim of the study was to investigate anti-CCA activity of the ethanolic extract of
Atractylodes lancea (Thunb.) DC., and the applicability of positron emission
tomography-computed tomography (PET-CT) as a tool for detection and monitoring
the progression of CCA in Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN)
induced CCA hamsters. Male Syrian hamsters were used for toxicity tests and anti
CCA activity evaluation. Development of CCA was induced by initial feeding of 50
metacercariae of OV, followed by drinking water containing 12.5 ppm of DMN in
hamsters. The ethanolic extract of A. lancea (Thunb.) DC. was administered orally
for 30 days. PET-CT was performed every 4 weeks after initiation of CCA using 18F
fluorodeoxyglucose (18F-FDG). Results from the present study suggest that the
ethanolic extract of A. lancea (Thunb.) DC. rhizome exhibited promising anti-CCA
activity and safety profile in the OV/DMN-induced hamster model. To successfully
apply PET-CT as a tool for early detection of tumor development and progression,
modification of radiolabeling approach is required to improve its specificity for
CCA cells.
PMID- 26434830
TI - Breast Cancer Screening in Morocco: Performance Indicators During Two Years of an
Organized Programme.
AB - BACKGROUND: Breast cancer is commonly diagnosed at late stages in countries with
limited resources. In Morocco, breast cancer is ranked the first female cancer
(36.1%) and screening methods could reduce the proportion presenting with a late
diagnosis. Morocco is currently adopting a breast cancer screening program based
on clinical examination at primary health facilities, diagnosis at secondary
level and treatment at tertiary level. So far, there is no systematic information
on the performance of the screening program for breast cancer in Morocco. The aim
of this study was to analyze early performance indicators. MATERIALS AND METHODS:
A retrospective evaluative study conducted in Temara city. The target population
was the entire female population aged between 45-70 years. The study was based on
process and performance indicators collected at the individual level from the
various health structures in Tamara between 2009 and 2011. RESULTS: A total of
2,350 women participated in the screening program; the participation rate was
35.7%. Of these, 76.8% (1,806) were married and 5.2% (106) of this group had a
family history of breast cancer. Of the women who attended screening, 9.3% (190)
were found to have an abnormal physical examination findings. A total of 260
(12.7%) were referred for a specialist consultation. The positive predictive
value of clinical breast examination versus mammography was 23.0%. Forty four
(35.5%) of the lesions found on the mammograms were classified as BI-RADs 3; 4 or
5 category. Cancer was found in 4 (1.95%) of the total number of screened women
and benign cases represented 0.58%. CONCLUSIONS: These first results of the
programme are very encouraging, but there is a need to closely monitor
performance and to improve programme procedures with the aim of increasing both
the participation rate and the proportion of women eligible to attend screening.
PMID- 26434831
TI - Expression of Bcl-2 in Primary and Recurrent Odontogenic Keratocysts in
Comparison with Other Odontogenic Lesions.
AB - PURPOSE: To determine the biological behaviour of common odontogenic cystic
lesions by analysing and comparing bcl-2 expression amongst them. MATERIALS AND
METHODS: Our study covered 90 formalin fixed paraffin embedded tissue samples: 26
primary cases each of radicular cysts (RC), dentigerous cysts (DC) and
odontogenic keratocysts (OKC) and 12 of recurrent OKCs. Bcl-2 expression was
analysed immunohistochemically and data analysis was accomplished using SPSS
version 17.0. Means were taken for age while for gender and site of the lesions
frequencies and percentages were determined. The Chi-square test was applied to
evaluate any statistically significant difference of bcl-2 expression in these
lesions and p value of <=0.05 was taken as significant. RESULTS: All the
recurrent OKCs showed a strong positivity for bcl-2 that was absent in all of its
primary cases (p value<0.05). Although variation in expression of bcl-2 was not
found to be statistically significant between RC and DC, however, it became
significant when all primary cases of these common odontogenic lesions were
compared. CONCLUSIONS: Recurrent OKC showed comparatively a more aggressive
behaviour than their primary counterparts and also from RC and DC. Bcl-2 proved
to be a valuable adjunct in determining aggressive biological behaviour of
odontogenic lesions.
PMID- 26434832
TI - Intentions to Undergo Lung Cancer Screening among Korean Men.
AB - Opportunistic screening for lung cancer is commonly conducted in Korea in
accordance with physician recommendations and screenee's preferences. However,
studies have yet to thoroughly examine the public's understanding of the risks
posed by lung cancer screening. This study was conducted to assess changes in
intentions to undergo lung cancer screening in response to being informed about
exposure to radiation during low-dose computed tomography (LDCT) tests and to
identify factors with the greatest influence thereon among Korean men. We
conducted sub-group interviews among men chosen from the 2013 Korea National
Cancer Screening Survey (KNCSS), a nationwide, population-based, cross-sectional
survey of men aged 40 to 74 years and women aged 30 to 74 years. From 4100
participants in the KNCSS, 414 men who underwent any cancer screening test within
the last 2 years were randomly selected for inclusion in this study. Via face-to
face interviews, their intentions to undergo lung cancer screening were assessed
before and after being informed about exposure to radiation during LDCT testing.
Of the 414 participants, 50% were current smokers. After receiving information on
the benefits of the test, 95.1% stated an intention to undergo screening; this
decreased to 81.6% after they received information on the harms of the test. The
average decrease in intention rate was 35.3%. Smoking status, household income,
and education level were not associated with lowered intentions to undergo lung
cancer screening. Participants who were older than 60 years old (OR=0.56; 95%
CI=0.33-0.96) and those with less concern for radiation exposure (OR=0.56; 95%
CI=0.36-0.89) were less likely to lower their screening intentions. The results
of this study suggest that there is a need to educate both non-smokers and former
smokers on the harms of lung cancer screening.
PMID- 26434833
TI - Is Exposure to Tobacco Advertising, Promotion and Sponsorship Associated with
Initiation of Tobacco Use among Current Tobacco Users in Youth in India?
AB - BACKGROUND: The rise in consumption of tobacco products among youth is a public
health concern in India. Several studies have shown that advertisements promoting
tobacco products influence decisions and behaviour of youth towards smoking.
OBJECTIVE: To ascertain which method of Tobacco Advertising, Promotion and
Sponsorship (TAPS) was more influential for initiating tobacco use in youth in
India. MATERIALS AND METHODS: The secondary data of youth (15-24 years) from
nationally representative Global Adult Tobacco Survey (GATS) conducted in 2009
2010 was analyzed. Odds ratio and p-value were used to know the association
between TAPS and initiation of use of tobacco products among youth. Logistic
regression was used to determine the most significant means of TAPS altering the
youth's behaviour towards tobacco products. RESULTS: Out of 13,383 youths, 1,982
(14.7%) used smokeless forms of tobacco and 860 (6.38%) used smoke forms.
Logistic regression reveals that promotional activities mainly through cinemas
(p<0.05) and providing free samples of tobacco products (p<=.001) were most
influential means of initiating consumption of tobacco products among youth.
CONCLUSIONS: The smoking in youth is associated with watching advertisements
particularly in cinema and promotional activities like distribution of free
samples, coupons and sales on the price of tobacco products. Stronger legislative
measures should be enforced to curb promotional advertisements in cinemas and
distribution of free samples.
PMID- 26434834
TI - Addressing Factors Associated with Arab Women's Socioeconomic Status May Reduce
Breast Cancer Mortality: Report from a Well Resourced Middle Eastern Country.
AB - Differences in socioeconomic status (SES) such as income levels may partly
explain why breast cancer screening (BCS) disparities exist in countries where
health care services are free or heavily subsidized. However, factors that
contribute to such differences in SES among women living in well resourced Middle
East countries are not fully understood. This quantitative study investigated
factors that influence SES and BCS of Arab women. Understanding of such factors
can be useful for the development of effective intervention strategies that aim
to increase BCS uptake among Arab women. Using data from a cross-sectional survey
among 1,063 Arabic-speaking women in Qatar, age 35+, additional data analysis was
performed to determine the relationship between socioeconomic indicators such as
income and other factors in relation to BCS activities. This study found that
income is determined and influenced by education level, occupation, nationality,
years of residence in the country, level of social activity, self-perceived
health status, and living area. Financial stress, unemployment, and unfavorable
social conditions may impede women's participation in BCS activities in well
resourced Middle East countries.
PMID- 26434835
TI - Staged Improvement in Awareness of Disease for Elderly Cancer Patients in
Southern China.
AB - BACKGROUND: In mainland China, awareness of disease of elderly cancer patients
largely relies on the patients' families. We developed a staged procedure to
improve their awareness of disease. MATERIALS AND METHODS: Participants were 224
elderly cancer patients from 9 leading hospitals across Southern China. A
questionnaire was given to the oncologists in charge of each patient to evaluate
the interaction between family and patients, patient awareness of their disease
and participation in medical decision-making. After first cycles of treatment,
increased information of disease was given to patients with cooperation of the
family. Then patient awareness of their disease and participation in medical
decision-making was documented. RESULTS: Among the 224 cancer elderly patients,
26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of
decision- making to their family. Subordinate family members tended to play a
passive role in decision-making significantly. Patients participating more in
medical decision-making tended to know more about their disease. However, in
contrast to the awareness of disease, patient awareness of violation of medical
recommendations was reversely associated with their participation in medical
decision-making. Improvement in awareness of diagnosis, stages and prognosis was
achieved in about 20% elderly cancer patients. About 5% participated more
actively in medical decision-making. CONCLUSIONS: Chinese elderly cancer patient
awareness of disease and participation in medical decision-making is limited and
relies on their family status. The staged procedure we developed to improve
patient awareness of disease proved effective.
PMID- 26434836
TI - Inhibitory Aromatase Effects of Flavonoids from Ginkgo Biloba Extracts on
Estrogen Biosynthesis.
AB - Ginkgo biloba extract (GBE) is a popular phytomedicine and has been used for
disorders of the central nervous system, cardiovascular, renal, respiratory, and
circulatory diseases. Although GBE is a complex mixture of over 300 compounds,
its major components are 24% flavonoids and 6% terpene lactones. In this study,
we tested the inhibitory effects of the three major flavonoids (kaempferol,
quercetin, and isorhamnetin) from GBE, independently and as mixtures, on
aromatase activity using JEG-3 cells (human placental cells) and recombinant
proteins (human placental microsome). In both systems, kaempferol showed the
strongest inhibitory effects among the three flavonoids; the flavanoid mixtures
exerted increased inhibitory effects. The results of exon I.1-driven luciferase
reporter gene assays supported the increased inhibitory effects of flavonoid
mixtures, accompanied by suppression of estrogen biosynthesis. In the RT-PCR
analysis, decreased patterns of aromatase promoter I.1 mRNA expressions were
observed, which were similar to the aromatase inhibition patterns of flavonoids
and their mixtures. The present study demonstrated that three flavonoids
synergistically inhibit estrogen biosynthesis through aromatase inhibition,
decrease CYP19 mRNA, and induce transcriptional suppression. Our results support
the usefulness of flavonoids in adjuvant therapy for breast cancer by reducing
estrogen levels with reduced adverse effects due to estrogen depletion.
PMID- 26434837
TI - 4G/5G and A-844G Polymorphisms of Plasminogen Activator Inhibitor-1 Associated
with Glioblastoma in Iran--a Case-Control Study.
AB - BACKGROUND: Glioblastoma is a highly aggressive and malignant brain tumor. Risk
factors are largely unknown however, although several biomarkers have been
identified which may support development, angiogenesis and invasion of tumor
cells. One of these biomarkers is PAI-1. 4G/5G and A-844G are two common
polymorphisms in the gene promotor of PAI 1 that may be related to high
transcription and expression of this gene. Studies have shown that the prevalence
of the 4G and 844G allele is significantly higher in patients with some cancers
and genetic disorders. MATERIALS AND METHODS: We here assessed the association of
4G/5G and A-844G polymorphisms with glioblastoma cancer risk in Iranians in a
case-control study. All 71 patients with clinically confirmed and 140 volunteers
with no history and symptoms of glioblastoma as control group were screened for
4G/5G and A-844G polymorphisms of PAI-1, using ARMS-PCR. Genotype and allele
frequencies of case and control groups were analyzed using the DeFinetti program.
RESULTS: Our results showed significant associations between 4G/5G (p=0.01824)
and A-844G (p=0.02012) polymorphisms of the PAI-1 gene with glioblastoma cancer
risk in our Iranian population. CONCLUSIONS: The results of this study supporting
an association of the PAI-1 4G/5G (p=0.01824) and A-844G (p=0.02012)
polymorphisms with increasing glioblastoma cancer risk in Iranian patients.
PMID- 26434838
TI - Palliative Care Education in Gynecologic Oncology: a Survey of Gynecologic
Oncologists and Gynecologic Oncology Fellows in Thailand.
AB - BACKGROUND: The main purpose of this study was to survey the education and
training of certified gynecologic oncologists and fellows in Thailand. A
secondary objective was to study the problems in fellowship training regarding
palliative care for gynecologic cancer patients. MATERIALS AND METHODS: A
descriptive study was conducted by sending a questionnaire regarding palliative
care education to all certified gynecologic oncologists and gynecologic oncology
fellows in Thailand. The contents of the survey included fellowship training
experience, caring for the dying, patient preparation, attitudes and respondent
characteristics. Statistics were analyzed by percentage, mean and standard
deviation and chi-square. RESULTS: One hundred seventy completed questionnaires
were returned; the response rate was 66%. Most certified gynecologic oncologists
and fellows in gynecologic oncology have a positive attitude towards palliative
care education, and agree that "psychological distress can result in severe
physical suffering". It was found that the curriculum of gynecologic oncology
fellowship training equally emphasizes three aspects, namely managing post
operative complications, managing a patient at the end of life and managing a
patient with gynecologic oncology. As for experiential training during the
fellowship of gynecologic oncology, education regarding breaking bad news,
discussion about goals of care and procedures for symptoms control were mostly on
the-job training without explicit teaching. In addition, only 42.9% of
respondents were explicitly taught the coping skill for managing their own stress
when caring for palliative patients during fellowship training. Most of
respondents rated their clinical competency for palliative care in the
"moderately well prepared" level, and the lowest score of the competency was the
issue of spiritual care. CONCLUSIONS: Almost all certified gynecologic
oncologists and fellows in gynecologic oncology have a positive attitude towards
learning and teaching in palliative care. In this study, some issues were
identified for improving palliative care education such as proper training under
the supervision of a mentor, teaching how to deal with work stress, competency in
spiritual care and attitudes on responsibility for bereavement care.
PMID- 26434839
TI - Expression of Cytoplasmic 8-oxo-Gsn and MTH1 Correlates with Pathological Grading
in Human Gastric Cancer.
AB - BACKGROUND: Cancers have dysfunctional redox regulation resulting in production
of reactive oxygen species (ROS), damaging DNA, RNA and free NTPs, and causing
the accumulation of oxidative nucleic acids in cytoplasm. The major types are 8
oxo-7,8-dihydroguanine(8-oxoGsn) in RNA and 8-oxo-7,8-dihydro-2' deoxyguanosine(8
oxodGsn) in Mt-DNA. The MTH1 protein sanitizes oxidized nucleotide pools from
NTPs to monophosphates, preventing the occurrence of transversion mutations. This
study concerned cytoplasmic 8-oxodGsn/Gsn and MTH1 expression in gastric cancer
and para-cancer tissues and elucidated roles of nucleic-acid oxidation and anti
oxidation. MATERIALS AND METHODS: A polymer HRP detection system was used to
detect 8-oxo-Gsn/dGsn and MTH1 expression in 51 gastric cancer and para-cancer
tissue samples. Analyses of patient clinical and pathological data were also
performed. RESULTS: The expression of MTH1 and the 8-oxo-dGsn/Gsn ratio were
significantly higher in cancer tissues than para-cancer tissues (P<0.05).
Cytoplasmic 8-oxo-Gsn and MTH1 were both found to positively correlate (P<0.05)
with tumor differentiation, while no significant associations were found with
gender, age, invasion depth, lymph node metastasis and clinical stage (P>0.05).
CONCLUSIONS: We found 8-oxo-dGsn/Gsn and MTH1 are both highly expressed in
gastric cancer tissues, especially in well differentiated lesions. In addition,
oxidated mtDNA is prevalently expressed in gastric cancers, while 8-oxo-Gsn
expression in cytoplasmic RNA is a bit lower, but more selectively.
PMID- 26434840
TI - Supportive Care Needs of Iranian Cancer Survivors and Relationships with Social
Support.
AB - BACKGROUND: Assessment of supportive care needs of cancer survivors and
identifying factors affecting such needs is important for implementation of any
supportive care programs. So, the aims of present study were to investigate the
supportive care needs of Iranian cancer survivors and relationships with social
support. MATERIALS AND METHODS: In this descriptive-correlational study two
hundred and fifty cancer survivors participated via convenient sampling methods.
The Supportive Care Needs Survey (SCNS-SF34) and Multidimensional Scale of
Perceived Social Support (MSPSS) were used for data collection. SPSS software was
applied and univariate regression was used for examine relationships of
supportive care needs with social support. RESULTS: Participants demonstrated
many unmet supportive care needs, especially in health system and information and
psychological domains. In addition, participants reported that family members and
significant others were their main source of support. Also, social support has a
significant correlation with all domains of supportive care needs. CONCLUSIONS:
There is an indispensable need for establishment of supportive care programs for
Iranian cancer survivors. In addition, family members of family members of such
survivors are an important resource to help develop such programs.
PMID- 26434841
TI - Evaluation of Common Risk Factors for Breast Carcinoma in Females: a Hospital
Based Study in Karachi, Pakistan.
AB - BACKGROUND: Breast malignancies are one of the leading causes of deaths in
females worldwide. There are a number of risk factors associated with breast
cancer but in Karachi Pakistan there are insufficient data available. MATERIALS
AND METHODS: A case control study was conducted on females in age group between
30-80 years. This study was accomplished by retrospective data collection in Aga
Khan University Hospital Karachi, Pakistan. A total of 108 females with primary
malignancy of breast were included along with 108 matched controls. Relationship
of various factors with disease was studied using logistic regression to
calculate odds ratios with 95 % confidence intervals. RESULTS: A total of 14
variables were analyzed and based on and 7 were found to be risk factors: old
age, family history of breast cancer, family history of other carcinomas,
personal history of breast carcinoma, early age of menarche, older age of mother
at first delivery and lower number of children. Five factors, parity, breast
feeding, history of oral contraceptive pills intake, past history of oophorectomy
and hysterectomy showed protective associations. One variable, use of hormonal
replacement therapy, showed a controversial link and one other, marital status,
was not significant in this study. CONCLUSIONS: It is concluded that most of the
well-known risk factors for breast cancer are also associated with the disease in
the female population of Karachi, Pakistan. High risk patients should be the
focus with the help of this study so that screening can be more effective for
early diagnosis before clinically evident breast malignancy.
PMID- 26434842
TI - Laparoscopic Versus Open Radical Cystectomy for Patients Older than 75 Years: a
Single-Center Comparative Analysis.
AB - BACKGROUND: To explore the safety, efficacy, and oncological outcome of 3-port
laparoscopic radical cystectomy (LRC) compared to open radical cystectomy (ORC)
in patients older than 75 years. MATERIALS AND METHODS: From June 2010 to July
2014, we analyzed 16 radical cystectomies in patients older than 75 years (LRC
group=8; ORC group=8). Demographic parameters, operative variables, and
perioperative outcome in the 2 groups were retrospectively collected, analyzed,
and compared. RESULTS: Patients in both groups had comparable preoperative
characteristics. A significantly longer operating time (476 vs. 303 min,
P=0.0002) and less estimated blood loss (627 vs. 2,106 mL, P=0.021) were observed
in the LRC group compared to the ORC group. Infection and ileus were the most
common early complications after surgery. Patients who underwent ORC suffered
from more postoperative infection (22.2% vs. 0.0%, P=0.054) and ileus (25.0% vs.
12.5%, P=0.521) than the LRC group, but the difference was not significant.
CONCLUSIONS: Judging from this initial trial, 3-port LRC can be safely carried
out in elderly patients. We suggest 3-port LRC as the primary intervention to
treat muscle-invasive or high-risk nonmuscle-invasive bladder cancer in elderly
patients with an otherwise relatively long life expectancy.
PMID- 26434843
TI - Aromatase Inhibition and Capecitabine Combination as 1st or 2nd Line Treatment
for Metastatic Breast Cancer - a Retrospective Analysis.
AB - BACKGROUND: Preclinical studies have shown that the combination of an aromatase
inhibitor (AI) and capecitabine in estrogen receptor (ER)-positive cell lines
enhance antitumor efficacy. This retrospective analysis of a group of patients
with metastatic breast cancer (MBC) evaluated the efficacy and safety of combined
AI with capecitabine. MATERIALS AND METHODS: Patients with hormone receptor
positive metastatic breast cancer treated between 1st January 2005 and 31st
December 2010 with a combination of capecitabine and AI were evaluated and
outcomes were compared with those of women treated with capecitabine in
conventional dose or AI as a monotherapy. RESULTS: Of 72 patients evaluated, 31
received the combination treatment, 22 AI and 19 capecitabine. The combination
was used in 20 patients as first-line and 11 as second-line treatment. Mean age
was 46.2 years with a range of 28-72 years. At the time of progression, 97% had a
performance status of <2 and 55% had visceral disease. No significant difference
was observed between the three groups according to clinical and pathological
features. Mean follow up was 38 months with a range of 16-66 months. The median
PFS of first-line treatment was significantly better for the combination (PFS 21
months vs 8.0 months for capecitabine and 15.0 months for AI). For second-line
treatment, the PFS was longer in the combination compared with capecitabine and
Al groups (18 months vs. 5.0 months vs. 11.0 months, respectively). Median 2 year
and 5 year survival did not show any significant differences among combination
and monotherapy groups. The most common adverse events for the combination group
were grade 1 and 2 hand-for syndrome (69%), grade 1 fatigue (64%) and grade 1
diarrhoea (29%). Three grade 3 hand-foot syndrome events were reported.
CONCLUSIONS: Combination treatment with capecitabine and AI used as a first line
or second line treatment was safe with much lowered toxicity. Prospective
randomized clinical trials should evaluate the use of combination therapy in
advanced breast cancer to confirm these findings.
PMID- 26434844
TI - Women and Tobacco Use: Discrepancy in the Knowledge, Belief and Behavior towards
Tobacco Consumption among Urban and Rural Women in Chhattisgarh, Central India.
AB - BACKGROUND: Tobacco consumption has become pandemic, and is estimated to have
killed 100 million people in the 20th century worldwide. Some 700,000 out of 5.4
million deaths due to tobacco use were from India. The era of global
modernization has led to an increase in the involvement of women in tobacco
consumption in the low income and middle-income countries. Tobacco consumption by
females is known to have grave consequences. OBJECTIVES: To assess: (1) the
tobacco use among urban and rural women; (2) the discrepancy in the knowledge,
belief and behavior towards tobacco consumption among urban and rural women in
Durg-Bhilai Metropolitan, Chhattisgarh, Central India. MATERIALS AND METHODS: The
study population consisted of 2,000 18-25 year old young women from Durg-Bhilai
Metropolitan, Chhattisgarh, Central India, from both urban and rural areas. Data
were collected using a pretested, anonymous, extensive face to face interview by
a female investigator to assess the tobacco use among women and the discrepancy
in the knowledge, belief and behavior towards tobacco consumption among urban and
rural individuals. RESULTS: The prevalence of tobacco use was found to be 47.2%.
Tobacco consumption among rural women was 54.4% and in urban women was 40%. The
majority of the women from urban areas (62.8%) were smokers whilst rural women
(77.4%) showed preponderance toward smokeless tobacco use. Urban women had a
better knowledge and attitude towards harms from tobacco and its use than the
rural women. Women in rural areas had higher odds (1.335) of developing tobacco
habit than the urban women. CONCLUSIONS: Increased tobacco use by women poses
very severe hazards to their health, maternal and child health, and their family
health and economic well-being. Due to the remarkably complex Indian picture of
female tobacco use, an immediate and compulsory implementation of tobacco control
policies laid down by the WHO FCTC is the need of the hour.
PMID- 26434845
TI - Age Specific Cytological Abnormalities in Women Screened for Cervical Cancer in
the Emirate of Abu Dhabi.
AB - BACKGROUND: Cervical cancer is the second most common cancer in women worldwide,
with about 500,000 new cases and 270,000 deaths each year. Globally, it is
estimated that over one million women currently have cervical cancer, most of
whom have not been diagnosed, or have no access to treatment that could cure them
or prolong their lives. In the United Arab Emirates (UAE) cervical cancer is the
third most common cancer in women. MATERIALS AND METHODS: A population-based
cross-sectional retrospective survey of cervical smear abnormalities was
conducted in the Emirate of Abu Dhabi, UAE, from January 2013 to December 2013 by
collecting consecutive liquid-based cytology samples from the Department of
Pathology at the SKMC Hospital in Abu Dhabi city. RESULTS: The total number of
women screened for cervical cancer for the year 2013 at SKMC was 4,593, with 225
(4.89%) abnormal smears. The majority of the abnormal smear results were atypical
squamous cells of undetermined significance (ASCUS) 114 (2.48%). This study
showed 60% increase in the rate of abnormal cervical smears in the UAE over the
last 10 years. In this study the highest incidence of high grade abnormalities
were seen in women above the age of 61 years (1.73%), this might be due to the
fact that this group of women missed the chance of screening of cervical cancer
earlier in their lives or could be explained by the well-known second peak of HPV
infection seen in many prevalence studies. CONCLUSIONS: We conclude that the rate
of abnormal cervical smear in the screened Abu Dhabi women is not different from
the rate in developed countries. A notable increase in both low and high grade
abnormalities has occurred within the last decade.
PMID- 26434846
TI - Whole Liver Palliative Radiotherapy for Patients with Massive Liver Metastases.
AB - BACKGROUND: The purpose of this retrospectively study was to examine the
effectiveness and tolerability of a radiotherapy technique for the palliation of
symptomatic liver metastases. MATERIALS AND METHODS: Twenty-seven patients with
liver metastases were enrolled and received targeted whole liver irradiation
consisting of mean 1, 8 Gy in five to twelve fractions to a total mean dose 17
Gy. Symptoms at baseline were hepatic pain (26 patients), lost of weight (6),
lack of appetite (2), and night sweats (1). Seventeen patients (63%) had failed
previous treatment with chemotherapy and/or high-dose steroids. RESULTS:
Individual symptom response rates were 100% at 4 weeks. Partial or complete
global symptomatic responses were noted in 11 patients (40%) after 2 months.
After 3 months, 8 patients (28%) reported loss of pain. The treatment was well
tolerated with one patient (3%) experiencing grade 3 toxicity (one vomiting and
one diarrhoea). Overall the median survival time was 4.9 months (range 1-14
months). One year survival was 39%. CONCLUSIONS: This is simple and well
tolerated treatment but to achieve good palliation effects we should carefully
selected patients whose conventional treatment does not bring good analgesic
control.
PMID- 26434847
TI - Polymorphism of the DNA Repair Gene XRCC1 (Arg194Trp) and its role in Colorectal
Cancer in Kashmiri Population: a Case Control Study.
AB - BACKGROUND: Genetic polymorphisms in DNA repair genes may influence individual
variation in DNA repair capacity, which may be associated with risk of developing
cancer. For colorectal cancer the importance of mutations in mismatch repair
genes has been extensively documented. MATERIALS AND METHODS: In this study we
focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in
base excision repair (BER) and its role in colorectal cancer in Kashmiri
population. A case-control study was conducted including 100 cases of colorectal
cancer, and 100 hospital-based age- and sex-matched healthy controls to examine
the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk
for the Kashmiri population. RESULTS: Genotype analysis of XRCC1 Arg194Trp was
conducted with a restriction fragment length polymorphism (RFLP) method. The
overall association between the XRCC1 polymorphism and the CRC cases was found to
be significant (p<0.05) with both the heterozygous genotype (Arg/Trp) as well as
homozygous variant genotype (Trp/Trp) being moderately associated with the
elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)]
respectively. CONCLUSIONS: Our results suggest an increased risk for CRC in
individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway
modulates the risk of developing colorectal cancer in the Kashmiri population.
PMID- 26434848
TI - Cervical Cancer Mortality Trends in China, 1991-2013, and Predictions for the
Future.
AB - BACKGROUND: To analyze cervical cancer mortality trends in China from 1991-2013
and forecast the mortality distribution in future five years (2014-2018), and
provide clues for prevention and treatment. MATERIALS AND METHODS: Mortality data
for cervical cancer in China from 1991 to 2013 were used to describe the
epidemiological characteristics and distribution, including the trend of the
standardized mortality rate, urban-rural differences, and age variation. Trend
surface analysis was used to analyze the geographical distribution of mortality.
Curve estimation, time series, gray modeling, and joinpoint regression were
performed to predict and forecast mortality trends. RESULTS: In recent years, the
mortality rate of cervical cancer has increased, and there is also a steady
increase in the incidence from 2003 to 2013 in China. Mortality rates in rural
areas are higher than in urban areas. The mortality dramatically increases in the
40+ yr age group, reaching a peak in the >85 yr age group. In addition,
geographical analysis showed that the cervical cancer mortality increased from
the southwest to west-central and from the southeast to northeast of the country.
CONCLUSIONS: The incidence rate and the mortality rate are increasing from 1991
to 2013, and the predictions show this will continue in the future. Thus,
implementation of prevention and management programs for cervical cancer are
necessary in China, especially for rural areas, young women in urban areas, and
high risk regions (the west-central).
PMID- 26434849
TI - Arsenic Exposure and Haematological Derangement in Cervical Cancer Cases in
India.
AB - Cervical cancer is the second most common gynecological malignancy worldwide.
According to HPV Information Centre, Spain (Aug'2014), in India approximately
1,22,844 women are diagnosed with the disease every year and of them 67,477 die
due to the disease. CaCx is said to be mediated by HPV but recent data published
reveal the role of Oxidative Stress in different Cancers. Arsenic is also one of
the agents for causing Oxidative Stress. Arsenic has been linked with different
types of cancer. Arsenic is considered responsible for generation of free
radicals and eventually for apoptosis. Early diagnosis of CaCx is presently a
matter of concern and clinical presentation in advanced stages become difficult
for complete clinical response. For determination of oxidative stress,
Malondialdehyde (MDA) was taken as an identifier and arsenic estimation was
performed with the help of Atomic Absorption Spectrometer (AAS). RBC count and
Haemoglobin levels were performed according to standard protocol. MDA was in
direct proportion with arsenic concentration and inversely proportional to RBC
and Haemoglobin in CaCx patients. Arsenic is one of the major causative agents
for oxidative stress and hence may be a risk factor leading to cancer including
CaCx.
PMID- 26434850
TI - Diagnostic Performance of Diffusion-Weighted Imaging for Multiple Hilar and
Mediastinal Lymph Nodes with FDG Accumulation.
AB - BACKGROUND: It is sometimes difficult to assess patients who have multiple hilar
and mediastinal lymph nodes (MHMLN) with FDG accumulation in PET-CT. Since it is
uncertain whether diffusion-weighted magnetic resonance imaging (DWI) is useful
in the assessment of such patients, its diagnostic performance was assessed.
MATERIALS AND METHODS: Twenty-three patients who had three or more stations of
hilar and mediastinal lymph nodes with SUVmax of 3 or more in PET-CT were
included in this study. RESULTS: For diagnosis of disease, there were 20
malignancies (lung cancers 17, malignant lymphomas 2 and metastatic lung tumor
1), and 3 benign cases (sarcoidosis 2 and benign disease 1). For diagnosis of
lymph nodes, there were 7 malignancies (metastasis of lung cancer 7 and malignant
lymphoma 1) and 16 benign lymphadenopathies (pneumoconiosis/silicosis 7,
sarcoidosis 4, benign disease 4, and atypical lymphocyte infiltration 1). The ADC
value (1.57+/-0.29x10(-3) mm2/sec) of malignant MHMLN was significantly lower
than that (1.99+/-0.24x10(-3) mm2/sec) of benign MHMLN (P=0.0437). However, the
SUVmax was not significantly higher (10.0+/-7.34 as compared to 6.38+/-4.31)
(P=0.15). The sensitivity (86%) by PET-CT was not significantly higher than that
(71%) by DWI for malignant MHMLN (P=1.0). The specificity (100%) by DWI was
significantly higher than that (31%) for benign MHMLN (P=0.0098). Furthermore,
the accuracy (91%) with DWI was significantly higher than that (48%) with PET-CT
for MHMLN (P=0.0129). CONCLUSIONS: Evaluation by DWI for patients with MHMLN with
FDG accumulation is useful for distinguishing benign from malignant conditions.
PMID- 26434851
TI - Predictive Value of the Platelet-To-Lymphocyte Ratio in Diagnosis of Prostate
Cancer.
AB - PURPOSE: To predict prostatic carcinoma using a logistic regression model on
prebiopsy peripheral blood samples. MATERIALS AND METHODS: Data of a total of 873
patients who consulted Urology Outpatient Clinics of Fatih Sultan Mehmet Training
and Research Hospital between February 2008 and April 2014 scheduled for prostate
biopsy were screened retrospectively. PSA levels, prostate volumes, prebiopsy
whole blood cell counts, neutrophil and platelet counts, neutrophil-to-lymphocyte
ratio (NLR), platelet-to-lymphocyte ratio (PLR), biopsy results and Gleason
scores in patients who had established diagnosis of prostate cancer (PCa) were
evaluated. RESULTS: This study was performed on a total of 873 cases, with an age
range 48-76 years, divided into three groups as for biopsy results. with
diagnoses of benign prostatic hyperplasia (BPH) (n=304, 34.8 %), PCa (n=265,
30.4%) and histological prostatitis (n=304; 34.8%). Intra- and intergroup
comparative evaluations were performed. White blood cell and neutrophil counts in
the histological prostatitis group were significantly higher than those of the
BPH and PCa groups (p=0.001; p=0.004; p<0.01). A statistically significant
intergroup difference was found for PLR (p=0.041; p<0.05) but not lymphocyte
count (p>0.05). According to pairwise comparisons, PLR were significantly higher
in the PCa group relative to BPH group (p=0.018, p<0.05, respectively). Though
not statistically significant, higher PLR in cases with PCa in comparison with
the prostatitis group was remarkable (p=0.067, and p>0.05, respectively).
CONCLUSIONS: Meta-analyses showed that in patients with PSA levels over 4 ng/ml,
positive predictive value of PSA is only 25 percent. Therefore, novel markers
which can both detect clinically significant prostate cancer, and also prevent
unnecessary biopsies are needed. Relevant to this issue in addition to PSA
density, velocity, and PCA3, various markers have been analyzed. In the present
study, PLR were found to be the additional predictor of prostatic carcinoma.
PMID- 26434852
TI - Temporal Epidemiological Assessment of Colorectal Cancer Incidence and Mortality
in East Kazakhstan, 2004-2013.
AB - Colorectal cancer incidence and mortality in Kazakhstan are relatively high but
exact statistics have hitherto been lacking and trends over time are unclear. The
present study was therefore undertaken to retrospectively assess data for East
Kazakhstan, accessed from the central registration office, for the period 2004
2013. Approximate age standardized data for incidence and mortality were
generated and compared across age groups, gender and year. It was determined that
during the studied period 3,417 new cases of colorectal cancer were registered
and 2,259 died of this pathology. Average cancer cancer incidence and mortality
over the ten years were 24.1/105 and 15.9/105 respectively, and the overall ratio
of mortality/incidence (M/I) was 0.69:1 (range 0.58-0.73). Both incidence and
mortality tended to remain constant in both males and females. The male to female
ratios also did not significantly vary over time but a trend for improvement of
the mortality to incidence ratio was observed, especially for rectum. Whether
this might be related to screening remains unclear. These preliminary data
indicate that whereas colorectal cancer continues to be important, change in
environmental factors are not having a great impact on incidence in East
Kazakhstan.
PMID- 26434853
TI - Viscum Album Var Hot Water Extract Mediates Anti-cancer Effects through G1 Phase
Cell Cycle Arrest in SK-Hep1 Human Hepatocarcinoma cells.
AB - Viscum album var (VAV) also known as mistletoe, has long been categorized as a
traditional herbal medicine in Asia. In addition to its immunomodulating
activities, mistletoe has also been used in the treatment of chronic hepatic
disorders in China and Korea. There are numerous reports showing that VAV
possesses anti-cancer effects, however influence on human hepatocarcinoma has
never been elucidated. In the present study, hot water extracts of VAV was
evaluated for its potential anti-cancer effect in vitro. SK-Hep1 cells were
treated with VAV (50-400 ug/ml) for both 24 and 48 hours then cell viability was
measured by cell counting kit-8 (CCK-8). Flow cytometry analysis was used to
measure the proportion of SK-Hep1 in the different stages of cell cycle. RT-PCR
and Western blot analysis were conducted to measure expression of cell cycle
arrest related genes and proteins respectively. VAV dose dependently inhibited
the proliferation of SK-Hep1 cells without any cytotoxicity with normal Chang
liver cell (CCL-13). Flow cytometry analysis showed that VAV extract inhibited
the cell cycle of SK-Hep1 cells via G1 phase arrest. RT-PCR and Western blot
analysis both revealed that cyclin dependent kinase 2 (Cdk2) and cyclin D1 gene
expression were significantly down regulated while p21 was upregulated dose
dependently by VAV treatment. Combined down regulation of Cdk2, Cyclin D1 and up
regulation of p21 can result in cell death. These results indicate that VAV
showed evidence of anti-cancer activity through G1 phase cell cycle arrest in SK
Hep1 cells.
PMID- 26434854
TI - In Vitro Anticancer Activities of Anogeissus latifolia, Terminalia bellerica,
Acacia catechu and Moringa oleiferna Indian Plants.
AB - The present study was designed to evaluate in vitro anti-proliferative potential
of extracts from four Indian medicinal plants, namely Anogeissus latifolia,
Terminalia bellerica, Acacia catechu and Moringa oleiferna. Their cytotoxicity
was tested in nine human cancer cell lines, including cancers of lung (A549),
prostate (PC-3), breast (T47D and MCF-7), colon (HCT-16 and Colo-205) and
leukemia (THP-1, HL-60 and K562) by using SRB and MTT assays. The findings showed
that the selected plant extracts inhibited the cell proliferation of nine human
cancer cell lines in a concentration dependent manner. The extracts inhibited
cell viability of leukemia HL-60 and K562 cells by blocking G0/G1 phase of the
cell cycle. Interestingly, A. catechu extract at 100 MUg/mL induced G2/M arrest
in K562 cells. DNA fragmentation analysis displayed the appearance of a smear
pattern of cell necrosis upon agarose gel electrophoresis after incubation of HL
60 cells with these extracts for 24 h.
PMID- 26434855
TI - Glutathione S-transferase M1 and T1 Polymorphisms, Cigarette Smoking and HPV
Infection in Precancerous and Cancerous Lesions of the Uterine Cervix.
AB - Glutathione S-transferases (GSTs) play an important role in detoxification of
carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been
implicated in carcinogenesis. Present study was planned to evaluate the influence
of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis.
The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical
scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD
and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was
extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using
L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by
multiplex PCR procedures. Differences in proportions were tested using Pearson's
Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk
of cervical cancer was almost three times in women with GSTM1 homozygous null
genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1
homozygous null genotypes was observed in women with normal, precancerous and
cervical cancerous lesions among <=35 or >35 years of age groups. Smokers with
null GSTT1 genotype had a higher risk of cervical cancer as compared to non
smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a
significant increased risk of cervical cancer was observed in HPV positive smoker
women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95%
CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non
smokers. The results demonstrate that the GST null genotypes were alone not
associated with the development of cervical cancer, but interacted with smoking
and HPV to exert effects in our Delhi population.
PMID- 26434856
TI - Exploratory Study to Evaluate Changes in Serum Lipid Levels as Early Diagnostic
and/or Prognostic Indicators for Oral Submucous Fibrosis and Cancer among Gutkha
Consumers in India.
AB - BACKGROUND: In India smokeless tobacco users account for 25.9% of total tobacco
use, Gutkha being the most common form. This study evaluated the association
between serum lipid profile and Gutkha use as an early diagnostic and/or
prognostic indicator for oral submucous fibrosis (OSMF) and oral cancer (Oral Ca)
in non-smokers and non-alcohol consumers. MATERIALS AND METHODS: A total of 163
participants were recruited from two sites in India. Participants were divided
into four groups: individuals without any Gutkha chewing habit and without any
oral lesions (control group), individuals with Gutkha chewing habit but without
any oral lesions (GWL), patients with a confirmed clinical diagnosis of OSMF, and
patients with a confirmed diagnosis of Oral Ca. Mixed linear modelling (MLM) was
conducted to detect the change in mean serum lipid levels among four groups.
RESULTS: The sample consisted of 69% males and 31% females. Results of MLM show
an inverse relationship between serum lipid levels in OSMF, and Oral Ca groups
when compared to the control group. CONCLUSIONS: The results of our study
demonstrated that GWL, OSMF and Oral Ca patients had lower serum lipid levels.
Low serum lipid levels could be an indicator of initial neoplastic changes in
oral cancer.
PMID- 26434857
TI - Cell Free EGFR mRNA Expression and Implications for Survival and Metastasis in
Non-Small Cell Lung Cancer Cases.
AB - BACKGROUND: NSCLC is a disease involving uncontrolled cell growth, which could
result in metastases into nearby tissues beyond the lungs. MATERIALS AND METHODS:
The aim of the present study was to analyze the influence of epidermal growth
factor receptor (EGFR) gene expression on metastasis and survival in NSCLC
patients. The present case-control study included 100 cases of NSCLC patients and
100 age and sex matched controls. EGFR gene expression was analyzed by
quantitative real time PCR using serum RNA. Association with NSCLC patient
survival was analyzed by the Kaplan-Meier method. RESULTS: We analyzed EGFR gene
expression and observed mean increased gene expression of 13.5 fold in NSCLC
patients. Values reflected overall survival of patients with a median of 15.8
months in the cases of <13 fold increased gene expression vs 6.7 months with >13
fold increased EGFR gene expression (p=0.005). Distant metastatic patients with
<13 fold increased EGFR gene expression had 7.9 months of median survival time
while>13 fold increased EGFR gene expression had only 5 months of median survival
time (p=0.03). Non metastatic patients with <13 fold increased EGFR gene
expression had 18 months of median survival time as compared to only 7.1 months
with >13 fold increased expression. CONCLUSIONS: Higher cell free EGFR mRNA
expression may play an important role in causing distant metastases and reducing
overall survival of NSCLC patients in the Indian population.
PMID- 26434858
TI - Epidemiological Aspects of Osteosarcoma, Giant Cell Tumor and Chondrosarcoma
Musculoskeletal Tumors--Experience of the National Rehabilitation Institute,
Mexico City.
AB - BACKGROUND: Primary bone neoplasms are rare, contributing only 0.2% of the global
burden of all human malignancies. Osteosarcoma (OS) and chondrosarcoma (CS) are
the most common malignancies of bone. The giant cell tumor of bone (GCTb) is a
benign tumor with behavior characterized by osteolytic bone destruction. The OS,
CS and GCTb affect both sexes, all races and generally have incidence peaks
regarding the age of the patient which vary according to the tumor type. We
analyzed the incidences of OS, CS and GCTb and their relations with gender and
age in patients treated in the National Rehabilitation Institute (INR, for its
acronym in Spanish) over a period of nine years. MATERIALS AND METHODS: In the
study period, clinic pathological data for 384 patients were obtained with
clinical, radiological and histopathological diagnosis for OS, GCTb and CS. Data
analysis was performed using the chi-square and Fisher's exact tests. RESULTS:
From 2006 to 2014 were recorded 384 cases of bone malignancies in the database of
INR. The GCTb had the highest incidence (53.1%), followed by OS (31.3%) and
finally the CS (15.6%). The overall average age was 33.6+/-15.8 years and the
overall frequency of gender had a ratio of 1/1.03 male/female. The states with
the highest incidence were Distrito Federal and Estado de Mexico with 29.2% and
25.3% respectively. Malignant neoplasms of bone assessed in the course of nine
years show three significant increases in 2008, 2011 and 2014 (p=0.14). We found
association between sex and tumor type (p=0.03), GCTb and CS predominated in
females (54.9% and 56.6% respectively), while for the OS males were most affected
(59.1%). Age was different in relation with tumor type (p=0.0001), average age
was 24.3+/-11.2 years for OS, 34.5+/-13 years for GCTb and 49.2+/-18.5 years for
CS. Furthermore, associations of tumor type with topographic location of the
primary tumor (P=0.0001) were found. CONCLUSIONS: In this study we can see that
incidence of musculoskeletal tumor in our population is continuously increasing
and in nine years an approximately 200% increase of musculoskeletal tumor cases
was observed.
PMID- 26434859
TI - Single Nucleotide Polymorphisms in miR-149 (rs2292832) and miR-101-1 (rs7536540)
Are Not Associated with Hepatocellular Carcinoma in Thai Patients with Hepatitis
B Virus Infection.
AB - MicroRNAs directly and indirectly influence many biological processes such as
apoptosis, cell maintenance, and immune responses, impacting on tumor genesis and
metastasis. They modulate gene expression at the post- transcriptional level and
are associated with progression of liver disease. Hepatocellular carcinoma (HCC)
is a cancer which mostly occurs in males. There are many factors affect HCC
development, for example, hepatitis B virus (HBV), hepatitis C virus (HCV) and
human immunodeficiency virus (HIV), co-infection, environmental factors including
alcohol, aflatoxin consumption and host-related factors such as age, gender
immune response, microRNA and single nucleotide polymorphisms (SNPs). Chronic
infection with the hepatitis B virus is the major factor leading to HCC
progression since it causes the liver injury. At present, there are many reports
regarding the association of SNPs on miRNAs and the HCC progression. In this
research, we investigated the role of miR- 149 (rs2292832) and miR-101-1
(rs7536540) with HCC progression in Thai population. The study included 289 Thai
subjects including 104 HCC patients, 90 patients with chronic hepatitis B virus
infection (CHB) and 95 healthy control subjects. The allele and genotype of
rs2292832 and rs7536540 polymorphisms were determined by TaqMan real-time PCR
assay. Our results revealed no significant association between miR-149
(rs2292832) and miR-101-1 (rs7536540) and the risk of HCC in our Thai population.
However, this research is the first study of miR-149 (rs2292832) and miR-101-1
(rs7536540) in HCC in Thai populations and the results need to be confirmed with
a larger population.
PMID- 26434860
TI - Time--and Concentration--Dependent Effects of Resveratrol on miR 15a and miR16-1
Expression and Apoptosis in the CCRF-CEM Acute Lymphoblastic Leukemia Cell Line.
AB - BACKGROUND: Chemotherapy is one of the common approaches in treatment of cancers,
especially leukemia. However, drug resistance phenomena reduce the likelihood of
treatment success. Resveratrol is a herbal compound which through complicated
processes makes some selected cells sensitive to treatment and induction of
apoptosis. In the present study, the effects of resveratrol on the expression of
miR 15a and miR16-1 and apoptosis in the CCRF-CEM cell line were investigated.
MATERIALS AND METHODS: The CCRF-CEM cell line was cultured under standard
conditions and changes in miR 15a and miR 16-1 expression were analyzed by real
time-PCR technique, with attention to reveratrol dose and time dependence. Also,
apoptosis is evaluated by flow cytometry using annexin V and PI. RESULTS: CCRF
CEM cells underwent dose-dependent apoptotic cell death in response to
resveratrol. MiR 15a and miR 16-1 expression was up-regulated after 24 and 48
hours resveratrol treatment (p<0.05). CONCLUSIONS: The results of our study
indicate that resveratrol induces apoptosis in a time and dose- dependent manner
in CCRF-CEM cells. Also, increased expression level of miR 16-1 and miR 15a by
means of resveratrol in CCRF-CEM cells might have a role in apoptosis induction
and predisposition. According to our results resveratrol can be regarded as a
dietary supplement to improve efficacy of anti-leukemia therapies.
PMID- 26434861
TI - Diffusion Weighted Imaging Can Distinguish Benign from Malignant Mediastinal
Tumors and Mass Lesions: Comparison with Positron Emission Tomography.
AB - BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) makes it possible
to detect malignant tumors based on the diffusion of water molecules. It is
uncertain whether DWI is more useful than positron emission tomography-computed
tomography (PET-CT) for distinguishing benign from malignant mediastinal tumors
and mass lesions. MATERIALS AND METHODS: Sixteen malignant mediastinal tumors
(thymomas 7, thymic cancers 3, malignant lymphomas 3, malignant germ cell tumors
2, and thymic carcinoid 1) and 12 benign mediastinal tumors or mass lesions were
assessed in this study. DWI and PET-CT were performed before biopsy or surgery.
RESULTS: The apparent diffusion coefficient (ADC) value (1.51+/-0.46x10(-3)
mm2/sec) of malignant mediastinal tumors was significantly lower than that
(2.96+/-0.86x10(-3) mm2/sec) of benign mediastinal tumors and mass lesions
(P<0.0001). Maximum standardized uptake value (SUVmax) (11.30+/-11.22) of
malignant mediastinal tumors was significantly higher than that (2.53+/-3.92) of
benign mediastinal tumors and mass lesions (P=0.0159). Using the optimal cutoff
value (OCV) 2.21x10(-3) mm2/sec for ADC and 2.93 for SUVmax, the sensitivity
(100%) by DWI was not significantly higher than that (93.8%) by PET-CT for
malignant mediastinal tumors. The specificity (83.3%) by DWI was not
significantly higher than that (66.7%) for benign mediastinal tumors and mass
lesions. The accuracy (92.9%) by DWI was not significantly higher than that
(82.1%) by PET-CT for mediastinal tumors and mass lesions. CONCLUSIONS: There was
no significant difference between diagnostic capability of DWI and that of PET-CT
for distinguishing mediastinal tumors and mass lesions. DWI is useful in
distinguishing benign from malignant mediastinal tumors and mass lesions.
PMID- 26434862
TI - Predictors of Sun-Protective Practices among Iranian Female College Students:
Application of Protection Motivation Theory.
AB - PURPOSE: Given the importance of sun protection in the prevention of skin cancer,
this study was designed to determine predictors of sun-protective practices among
a sample of Iranian female college students based on protection motivation theory
(PMT) variables. MATERIALS AND METHODS: In this cross-sectional study, a total of
201 female college students in Iran University of Medical Sciences were selected.
Demographic and PMT variables were assessed with a 67-item questionnaire.
Multiple linear regression was used to identify demographic and PMT variables
that were associated with sun-protective practices and intention. RESULTS: one
percent of participants always wore a hat with a brim, 3.5% gloves and 15.9%
sunglasses while outdoors. Only 10.9% regularly had their skin checked by a
doctor. Perceived rewards, response efficacy, fear, self-efficacy and marital
status were the five variables which could predict 39% variance of participants
intention to perform sun-protective practices. Also, intention and response cost
explained 31% of the variance of sun-protective practices. CONCLUSIONS: These
predictive variables may be used to develop theory-based education interventions
interventions to prevent skin cancer among college students.
PMID- 26434863
TI - Patterns of Esophageal Cancer in the National Cancer Institute at the University
of Gezira, in Gezira State, Sudan, in 1999-2012.
AB - BACKGROUND: Esophageal cancer (EC) is among the most common malignancies in
Eastern Africa, but the occurrence of EC in Sudan has rarely been described in
the scientific literature. This paper reports the results of a consecutive case
series of all EC patients who visited one of the two public cancer treatment
centers in the country in 1999-2012, providing a first description of this
disease in a treatment center located in central Sudan. MATERIALS AND METHODS:
Clinical and demographic data for all EC patients who visited the Department of
Oncology of the National Cancer Institute at the University of Gezira (NCI-UG)
from 1999 to the end of 2012 were abstracted and tabulated by sex, tumor type and
other characteristics. RESULTS: A total of 448 EC patients visited NCI-UG in 1999
2012, and the annual number of EC cases increased steadily from 1999. Squamous
cell carcinoma (SCC) was the predominant EC tumor type (90%), and adenocarcinoma
(ADC) was reported in 9.4% of the EC cases. The overall male-to-female ratio for
EC was 1:1.8, but the ratio was tumor type-dependent, being 1:2 for SCC and 2:1
for ADC. Only 20% of EC patients reported having ever used tobacco and/or
alcohol, and the vast majority of these patients were male. At the time of EC
diagnosis, 47.3% of the patients resided in Gezira State. Some EC patients from
Gezira State seek out-of-state treatment in the national capital of Khartoum
instead of visiting NCI-UG. CONCLUSIONS: The annual number of EC patients
visiting NCI-UG has increased in recent years, approximately half of these
patients being from Gezira State. Although this consecutive series of EC patients
who visited NCI-UG was complete, it did not capture all EC patients from the
state. A population- based cancer registry would provide more complete data
required to better understand EC patterns and risk factors.
PMID- 26434864
TI - Chemopreventive Actions of Blond and Red-Fleshed Sweet Orange Juice on the Loucy
Leukemia Cell Line.
AB - BACKGROUND: Red-fleshed sweet orange juice (ROJ) comes from a new variety of
citrus cultivated in Brazil that contains high levels of beta-carotene and
lycopene, and similar amounts of hesperidin (HSP) and nutrients, equivalently to
blond orange juice (BOJ). Such bioactive compounds are associated with
chemopreventive actions in several cancer cell lines. The purpose of this study
was to examine the cytotoxicity, cell cycle, apoptosis, and cytokine secretion
after BOJ, ROJ, and HSP treatment of a novel T acute lymphoblastic leukemia cell
line, Loucy. MATERIALS AND METHODS: Loucy cells were incubated for 24-h with BOJ,
ROJ, and HSP, and the viability was measured using trypan blue. Cell cycling and
apoptosis were assessed by propidium iodide (PI) and annexin V-FITC/PI flow
cytometry, respectively. Secretion of cytokines IL-1alpha, IL1-beta, IL-2, IL-4,
IL-6, IL-10, IL-17A, IFNgamma, TNFalpha, TGFbeta, MIPalpha, and MIPbeta was
determined by ELISA array. RESULTS: BOJ and ROJ treatments promoted Loucy cell
cytotoxicity. Additionally, BOJ induced cell cycle arrest in the G0/G1 phase, and
decreased the cell accumulation in the G2/M. ROJ decreased only the G0/G1
fraction, while HSP did not change the cell cycle. BOJ led to apoptosis in a
different fashion of ROJ, while the first treatment induced apoptosis by increase
of late apoptosis and primary necrotic fractions, the second increased early and
late apoptosis, and primary necrotic fraction compared to positive controls. HSP
had no effect on apoptosis. IL-6 and IL-10 were abrogated by all treatments.
CONCLUSIONS: Taking together, these results suggest potential chemopreventive
effects of BOJ and ROJ on Loucy cells.
PMID- 26434865
TI - Bevacizumab Regulates Cancer Cell Migration by Activation of STAT3.
AB - There are numerous clinical cases indicating that long-term use of bevacizumab
may increase the invasiveness of tumors. However, to date, little is known about
underlying molecular mechanisms. Therefore, the purpose of our study was to
investigate effects of bevacizumab in four cancer cells lines (WSU-HN6, CAL27,
Tca83, and HeLa). It was found to promote migration and invasion in the WSU-HN6
and Tca83 cases, while exerting inhibitory effects in CAL27 and HeLa cells. The
signal transducer and activator of transcription (STAT) 3 inhibitors niclosamide
and S3I-201 inhibited the STAT3 signal pathway, which is activated by
bevacizumab. These inhibitors also substantially blocked bevacizumab-induced
migration of WSU-HN6 and Tca83 cells. Bevacizumab upregulated interleukin (IL)-6
and phosphorylated (p)-STAT3 expression time-dependently. Therefore, we propose
that bevacizumab has differential effects on the migration of different cancer
cell lines and promotes migration via the IL-6/STAT3 signaling pathway.
PMID- 26434866
TI - Medullary Thyroid Carcinoma--Circulating Status of Vaspin and Retinol Binding
Protein-4 in Iranian Patients.
AB - BACKGROUND: Vaspin and Retinol binding protein-4 (RBP4) are new adipokines mainly
produced by adipose tissue. Considering that medullary thyroid carcinoma (MTC) is
a malignant neuroendocrine tumor, and to date the relationship between serum
levels of vaspin and RBP4 with MTC has not been studied, in this matched case
control study we evaluated their possible significance to this tumor type.
MATERIALS AND METHODS: A total of 45 patients with MTC (21 males and 24 females)
and 45 healthy persons as a control group (24 males and 21 females) were
selected. The two groups were matched for age, sex and body mass index. Serum
Vaspin and RBP4 levels were measured by enzyme-linked immunosorbent assay (ELISA)
methods in both groups. Also, weight and height were measured and body mass index
was calculated too. RESULTS: In total, patients with MTC had significantly higher
serum vaspin levels compared to the controls (0.52 ng/ml vs. 0.45 ng/ml,
P=0.0241). However, no significant difference was found in serum RBP4
concentrations between the patients with MTC and the controls (15.2+/-2.55 MUg/ml
versus 15.1+/-3.34 MUg/ml, p>0.05). CONCLUSIONS: The results of this study
demonstrated that serum RBP4 levels in MTC patients are not significantly
different from those found in healthy individuals and did not correlate with MTC.
On the other hand, higher levels of serum vaspin are associated with an increased
risk of MTC. Thus Vaspin may be a novel and promising biomarker for diagnosis or
confirmation of MTC in conjunction other specific tumor markers.
PMID- 26434867
TI - Anticancer Effects of Curcuma C20-Dialdehyde against Colon and Cervical Cancer
Cell Lines.
AB - BACKGROUND: Recent attention on chemotherapeutic intervention against cancer has
been focused on discovering and developing phytochemicals as anticancer agents
with improved efficacy, low drug resistance and toxicity, low cost and limited
adverse side effects. In this study, we investigated the effects of Curcuma C20
dialdehyde on growth, apoptosis and cell cycle arrest in colon and cervical
cancer cell lines. MATERIALS AND METHODS: Antiproliferative, apoptosis induction,
and cell cycle arrest activities of Curcuma C20-dialdehyde were determined by WST
cell proliferation assay, flow cytometric Alexa fluor 488-annexin V/propidium
iodide (PI) staining and PI staining, respectively. RESULTS: Curcuma C20
dialdehyde suppressed the proliferation of HCT116, HT29 and HeLa cells, with IC50
values of 65.4+/-1.74 MUg/ml, 58.4+/-5.20 MUg/ml and 72.0+/-0.03 MUg/ml,
respectively, with 72 h exposure. Flow cytometric analysis revealed that
percentages of early apoptotic cells increased in a dose-dependent manner upon
exposure to Curcuma C20-dialdehyde. Furthermore, exposure to lower concentrations
of this compound significantly induced cell cycle arrest at G1 phase for both
HCT116 and HT29 cells, while higher concentrations increased sub-G1 populations.
However, the concentrations used in this study could not induce cell cycle arrest
but rather induced apoptotic cell death in HeLa cells. CONCLUSIONS: Our findings
suggest that the phytochemical Curcuma C20-dialdehyde may be a potential
antineoplastic agent for colon and cervical cancer chemotherapy and/or
chemoprevention. Further studies are needed to characterize the drug target or
mode of action of the Curcuma C20-dialdehyde as an anticancer agent.
PMID- 26434868
TI - Treatment and Follow-up of Human Papillomavirus Infected Women in a Municipality
in Southern Brazil.
AB - BACKGROUND: This study aimed toanalyze the risk behavior for cervical cancer (CC)
and the human papillomavirus (HPV) prevalence and resolution among women who
received care through the private healthcare network of a municipality in
southern Brazil. MATERIALS AND METHODS: This descriptive and retrospective study
was conducted with 25 women aged 20 to 59 years who received care through the
private healthcare network and were treated at a specialty clinic in the period
from January to December 2012 in a municipality in Northwest Parana, Southern
Brazil. Data from medical records with cytological and HPV results were used.
Following treatment, these women were followed-up and reassessed after 6 months.
Data were statistically analyzed using the t-test and chi-squared test at a 5%
significance level. RESULTS: The mean age of the studied women was 27.8+/-7.75
years old, and the majority were married, with paid employment and were non
smokers. The mean age at menarche was 13.0+/-0.50 years old, and the mean age at
first intercourse was 17.5+/-1.78 years, with only 8.0% (2) initiating sexual
activity at an age <=15 years old. The majority had 1 to 2 children (60.0%),
while 88.0% reported having had one sexual partner in their lifetime, and all the
women were sexually active. A total of 68.0% used a hormonal contraceptive
method. All the women had leukorrhea and pain and were infected by a single HPV
type. Regarding the lesion grade, 80.0% showed high risk and 20.0% low risk. The
most prevalent high-risk HPV strain was 16. CONCLUSIONS: These findings provide
relevant information on HPV risk factors and infection, as well as the treatment
and 6-month follow-up results, in economically and socially advantaged women with
no traditional risk factors, corroborating previous reports that different risk
factors may be described in different populations. Thus, this study reinforces
the fact that even women without the traditional risk factors should undergo
HPVmonitoring and assessment to determine the persistence of infection, promoting
early diagnosis of the lesions presented and appropriate treatment to thus
prevent the occurrence of CC.
PMID- 26434869
TI - Association between Smoking Status and Food and Nutrient Consumption in Japanese:
a Large-Scale Cross-Sectional Study.
AB - BACKGROUND: In Japan, in comparison with the rest of the world the death rate of
lung cancer is low although the smoking rate is relatively high. This is the so
called "Japanese smoking paradox". A healthy diet is proposed to attenuate the
risk without quitting smoking. We here examined the relationships between smoking
status (SS) and the consumption of food and nutrient in Japan. MATERIALS AND
METHODS: Totals of 5,587 men and 2,718 women were divided into three (non
smokers, smokers and heavy smokers) and two (non-smokers and smokers) groups,
respectively, according to pack-year, which represents the amount of smoking over
a long period. Food and nutrient consumption was estimated with a validated food
frequency questionnaire. Using general linear models, food and nutrient
consumption was estimated for each group in men and women, separately. RESULTS:
In men, SS was positively related to consumption of rice, 3 alcoholic beverages,
carbohydrate, alcohol and other 8 foods/nutrients (p<0.05 for all) and negatively
to those of protein animal, fat, fatty acids, dietary fiber, isoflavones and 36
other foods/nutrients (p<0.05 for all). In women, SS was positively associated
with intake of 13 foods/nutrients, while being negatively associated with those
of rice, energy, dietary fiber, and 14 other foods/nutrients (p<0.05 for all).
CONCLUSIONS: Our results support lower intake of vegetables and fruits rich in
antioxidants, which are thought as preventive factors for many diseases, in
smokers.
PMID- 26434870
TI - Nuclear DNA Damage and Repair in Normal Ovarian Cells Caused by Epothilone B.
AB - This study was designed to assess, whether a new chemotherapeutic microtubule
inhibitor, Epothilone B (EpoB, Patupilone), can induce DNA damage in normal
ovarian cells (MM14.Ov), and to evaluate if such damage could be repaired. The
changes were compared with the effect of paclitaxel (PTX) commonly employed in
the clinic. The alkaline comet assay technique and TUNEL assay were used. The
kinetics of DNA damage formation and the level of apoptotic cells were determined
after treatment with IC50 concentrations of EpoB and PTX. It was observed that
PTX generated significantly higher apoptotic and genotoxic changes than EpoB. The
peak was observed after 48 h of treatment when the DNA damage had a maximal
level. The DNA damage induced by both tested drugs was almost completely
repaired. As EpoB in normal cells causes less damage to DNA it might be a
promising anticancer drug with potential for the treatment of ovarian tumors.
PMID- 26434871
TI - Epidemiological Study of Laryngeal Carcinoma in Western Nepal.
AB - BACKGROUND: Laryngeal malignancy is a common malignancy of the head and neck
region. Affected patients usually present with features that are characteristic
of certain subsites. The larynx is oncologically divided into three:
supraglottis, glottis and subglottis. Studies from Western countries have shown
that the glottis is the commonest subsite to harbour laryngeal malignancy.
However, the supraglottis has been reported to be the commonest subsite in
developing countries, including examples in the Indian subcontinent. To our
knowledge, no study has been carried out in western Nepal about the epidemiology
of laryngeal cancer to date. The purpose of this study was to analyse the
epidemiology of laryngeal cancer in relation to its risk factors, age
distribution,and preferred subsites and to see if there is any recent change in
the subsite wise distribution of laryngeal malignancy in western Nepal. MATERIALS
AND METHODS: Patients of all ages and both sexes with suspected laryngeal
malignancy were enrolled in the initial study. Detailed history taking and
clinical examination was performed to find out the involved subsite in relation
to the clinical features. Direct laryngoscopy was performed to further confirm
the subsite and to take biopsy from the growth under general anesthesia. After
confirmation of malignancy from the biopsy report, patients were finally included
in the study. Data were analysed and observations were made to find out the
distribution of laryngeal malignancy in different subsites. RESULTS: The
supraglottic larynx was the commonest subsite to harbor laryngeal malignancy.
Smoking and alcohol were found to be the common risk factors. The mean age of the
patients was in their sixties. CONCLUSIONS: Laryngeal malignancy is common in
elderly individuals. Supraglottic laryngeal malignancy is the commonest laryngeal
malignancy in people who smoke and drink alcohol in Nepal. Avoidance of alcohol
use and smoking will be a milestone to reduce the incidence of laryngeal cancers
and associated mortality.
PMID- 26434872
TI - Transducer-like Enhancer of Split 1 as a Novel Immuno- histochemical Marker for
Diagnosis of Synovial Sarcoma.
AB - BACKGROUND: Synovial sarcoma is a mesenchymal neoplasm that accounts for around
10% of all soft tissue sarcomas. The diagnosis of synovial sarcoma can be a
challenging task, particularly with small biopsy specimens. AIM: We investigated
transducer-like enhancer of split 1 (TLE1), monoclonal antibody, expression by
immunohistochemical analysis in a group of 74 synovial sarcoma cases, 20 cases of
MPNST, 12 cases of neurofibroma, 15 cases of schwannoma, 5 cases of MFH, 10 cases
of lieomyosarcoma and 10 cases of solitary fibrous tumor. MATERIALS AND METHODS:
Whole tissue sections were examined: (39 biphasic and 35 monophasic). Nuclear
immunoreactivity was scored as negative (<5% of cells positive), 1+(mild /5-25%),
2+ (moderate/25-50%), and 3+ (strong >50%). RESULTS: Overall, 71 (96%) of 74
synovial sarcomas were positive for TLE1, including 37 biphasic (95%) and 34
monophasic (97%) tumors. Other spindle cell tumors showed very low or absent
staining of TLE1. CONCLUSIONS: We conclude that TLE1 is a sensitive marker and
can be a useful diagnostic marker for synovial sarcoma, particularly the
monophasic forms.
PMID- 26434873
TI - Mechanism of Chemoprevention against Colon Cancer Cells Using Combined Gelam
Honey and Ginger Extract via mTOR and Wnt/beta-catenin Pathways.
AB - The PI3K-Akt-mTOR, Wnt/beta-catenin and apoptosis signaling pathways have been
shown to be involved in genesis of colorectal cancer (CRC). The aim of this study
was to elucidate whether combination of Gelam honey and ginger might have
chemopreventive properties in HT29 colon cancer cells by modulating the mTOR,
Wnt/beta-catenin and apoptosis signaling pathways. Treatment with Gelam honey and
ginger reduced the viability of the HT29 cells dose dependently with IC50 values
of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2
mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells.
Gelam honey, ginger and combination induced apoptosis in a dose dependent manner
with the combined treatment exhibiting the highest apoptosis rate. The combined
treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, beta
catenin, Gsk3beta, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were
shown to be upregulated. In conclusion, the combination of Gelam honey and ginger
may serve as a potential therapy in the treatment of colorectal cancer through
inhibiton of mTOR, Wnt/beta catenin signaling pathways and induction of apoptosis
pathway.
PMID- 26434874
TI - Does Cervical Screening in Young Women Aged 20-25 Years Lead to Unnecessary and
Harmful Interventions?
AB - BACKGROUND: Cervical human papillomavirus (HPV) infection among young women (20
25 years of age) is common and normally transient. There are growing concerns
that referral to a colposcopy clinic may lead to unnecessary treatment with an
increased risk of obstetric complications. Therefore, the purpose of this study
was to determine the level of intervention for cervical abnormalities in this age
group of the Northern Ireland population. MATERIALS AND METHODS: A review of all
serial new patients under 25 years of age, who were referred to colposcopy
clinics in Northern Ireland between January 1, 2009 to June 30, 2009 formed the
basis of this study. RESULTS: During the study period, a total of 4,767 women
under 25 years of age were screened. Two-hundred-and- thirty-four (4.9%) cases
were referred to the colposcopy clinics. The cervical cytology results were: high
grade abnormality in 35%, and low-grade abnormality in 31% of these cases. One
hundred-and-seventy-eight (76%) of the referred women received at least one
treatment. One-hundred-and-twenty-one of 234 (51.5%) women underwent an
excisional treatment with histology showing the presence of high-grade
abnormalities (CIN2-3) in 52%, CIN1 in 28%, and Koilocytosis or normal tissue in
20% of this sub-group of cases. CONCLUSIONS: Screening women under the age of 25
years cause unnecessary referral for colposcopy. This may also result in
considerable anxiety and psychosexual morbidity. It leads to an over-treatment
with a potential of negative impact on the future pregnancy outcomes (including
pre-term delivery, low birth weight, and pre-term premature rupture of
membranes).
PMID- 26434875
TI - Trends of Smokeless Tobacco use among Adults (Aged 15-49 Years) in Bangladesh,
India and Nepal.
AB - BACKGROUND: Smokeless tobacco (SLT) has long been realized as an important
component of the fight for global tobacco control. It still remains a major
problem in countries like India, Bangladesh and Nepal. The objective of this
study was to estimate the trends of SLT use in three countries of the SEARO WHO
office. MATERIALS AND METHODS: We used data from national surveys in three
countries (Bangladesh, India and Nepal) to estimate trends in prevalence of
current SLT use. All available nationally representative data sources were used.
Estimates were weighted, age standardized and given along with 95% confidence
intervals. Significance of linear trend in prevalence over time was tested using
the Cochrane-Armitage test for trend. A p value of less than 0.05 was considered
statistically significant. RESULTS: We identified three surveys for Bangladesh,
three for India and four for Nepal that met the selection criteria (such as
Demographic and Health Surveys, WHO-STEPwise approach to Surveillance and Global
Adult Tobacco Surveys). A significantly increasing trend was noticed in the
prevalence of current SLT use among Bangladeshi men (20.2% to 23%, p=0.03). In
India, a similar significantly increasing trend was seen among men (27.1% to
33.4%, p<0.001) and women (10.1% to 15.7%, p<0.001). In Nepal, there was a no
significant trend among both men (39.1% to 31.6%, p=0.11) and women (5.6% to
4.7%, p=0.49). CONCLUSIONS: In the study countries SLT use has remained at
alarmingly high levels. Usage trends do not show any signs of decline in spite of
control efforts. Tobacco control measures should focus more on controlling SLT
use.
PMID- 26434876
TI - Applicative Value of Serum CA19-9, CEA, CA125 and CA242 in Diagnosis and
Prognosis for Patients with Pancreatic Cancer Treated by Concurrent
Chemoradiotherapy.
AB - OBJECTIVE: To evaluate the application value of serum CA19-9, CEA, CA125 and
CA242 in diagnosis and prognosis of pancreatic cancer cases treated with
concurrent chemotherapy. MATERIALS AND METHODS: 52 patients with pancreatic
cancer, 40 with benign pancreatic diseases and 40 healthy people were selected.
The electrochemiluminescence immunoassay method was used for detecting levels of
CA19-9, CEA and CA125, and a CanAg CA242 enzyme linked immunoassay kit for
assessing the level of CA242. The Kaplan-Meier method was used for analyzing the
prognostic factors of patients with pancreatic cancer. The Cox proportional
hazard model was applied for analyzing the hazard ratio (HR) and 95% confidential
interval (CI) for survival time of patients with pancreatic cancer. RESULTS: The
levels of serum CA19-9, CEA, CA125 and CA242 in patients with pancreatic cancer
were significantly higher than those in patients with benign pancreatic diseases
and healthy people (P<0.001). The sensitivity of CA19-9 was the highest among
these, followed by CA242, CA125 and CEA. The specificity of CA242 is the highest,
followed by CA125, CEA and CA19-9. The sensitivity and specificity of joint
detection of serum CA19-9, CEA, CA125and CA242 were 90.4% and 93.8%, obviously
higher than single detection of those markers in diagnosis of pancreatic cancer.
The median survival time of 52 patients with pancreatic cancer was 10 months (95%
CI7.389~12.611).. Patients with the increasing level of serum CA19-9, CEA, CA125,
CA242 had shorter survival times (P=0.047. 0.043, 0.0041, 0.029). COX regression
analysis showed that CA19-9 was an independent prognostic factor for patients
with pancreatic cancer (P=0.001, 95%CI 2.591~38.243). CONCLUSIONS: The detection
of serum tumor markers (CA19.9, CEA, CA125 and CA242) is conducive to the early
diagnosis of pancreatic cancer and joint detection of tumor markers helps improve
the diagnostic efficiency. Moreover, CA19-9 is an independent prognostic factor
for patients with pancreatic cancer.
PMID- 26434877
TI - Differences in Prognostic Factors between Early and Late Recurrence Breast
Cancers.
AB - BACKGROUND: Breast cancer (BC) is the most frequent malignancy among females and
is a leading cause of death of middle-aged women. Herein, we evaluated baseline
characteristics for BC patients and also compared these variables across ealry
and late recurrence groups. MATERIALS AND METHODS: Between 1995 to 2014, among
female breast cancer patients referred to our oncology clinic, eighty-six were
entered into our study. All had distant metastasis. Early recurrence was defined
as initial recurrence within 5 years following curative surgery irrespective of
site. Likewise, late recurrence was defined as initial recurrence after 5 years.
No recurrence was defined for survivors to a complete minimum of 10 years follow
up. Significant prognostic factors associated with early or late recurrence were
selected according to the Akaike Information Criterion. RESULTS: The median
follow-up was 9 years (range, 1-18 years). During follow-up period, 51
recurrences occurred (distant metastasis), 31 early and 20 late. According to the
site of recurrence, there were 51 distant. In this follow-up period, 19 patients
died. Compared with the early recurrence group, the no recurrence group had lower
lymph node involvement and more p53 positive lesions but the late recurrence
group had lower tumor size. In comparison to no recurrence, p53 (odds ratio [OR]
6.94, 95% CI 1.49-32.16) was a significant prognostic factor for early recurrence
within 5 years. CONCLUSIONS: Tumor size, p53 and LN metastasis are the most
important risk factors for distance recurrence especially in early recurrence and
also between of them, p53 is significant prognostic factor for early recurrence.
PMID- 26434878
TI - Propolis from the Stingless Bee Trigona incisa from East Kalimantan, Indonesia,
Induces In Vitro Cytotoxicity and Apoptosis in Cancer Cell lines.
AB - BACKGROUND: Previously, stingless bee (Trigona spp.) products from East
Kalimantan, Indonesia, were successfully screened for in vitro antiproliferative
activity against human cancer derived cell lines. It was established that
propolis from T. incisa presented the highest in vitro cytotoxicity against the
SW620 colon cancer cell line (6% cell survival in 20 MUg/mL). MATERIALS AND
METHODS: Propolis from T. incisa was extracted with methanol and further
partitioned with n-hexane, ethyl acetate and methanol. The in vitro cytotoxicity
of the extracts was assessed by the MTT assay against human colon (SW620), liver
(Hep-G2), gastric (KATO-III), lung (Chago) and breast (BT474) cancer derived cell
lines. The active fractions were further enriched by silica gel quick column,
absorption and size exclusion chromatography. The purity of each fraction was
checked by thin layer chromatography. Cytotoxicity in BT-474 cells induced by
cardanol compared to doxorubicin were evaluated by MTT assay, induction of cell
cycle arrest and cell death by flow cytometric analysis of propidium iodide and
annexin-V stained cells. RESULTS: A cardol isomer was found to be the major
compound in one active fraction (F45) of T. incisa propolis, with a cytotoxicity
against the SW620 (IC50 of 4.51+/-0.76 MUg/mL), KATO-III (IC50 of 6.06+/-0.39
MUg/mL), Hep-G2 (IC50 of 0.71+/-0.22 MUg/mL), Chago I (IC50 of 0.81+/-0.18
MUg/mL) and BT474 (IC50 of 4.28+/-0.14 MUg/mL) cell lines. Early apoptosis
(programmed cell death) of SW620 cells was induced by the cardol containing F45
fraction at the IC50 and IC80 concentrations, respectively, within 2-6 h of
incubation. In addition, the F45 fraction induced cell cycle arrest at the G1
subphase. CONCLUSIONS: Indonesian stingless bee (T. incisa) propolis had
moderately potent in vitro anticancer activity on human cancer derived cell
lines. Cardol or 5-pentadecyl resorcinol was identified as a major active
compound and induced apoptosis in SW620 cells in an early period (<=6 h) and cell
cycle arrest at the G1 subphase. Thus, cardol is a potential candidate for cancer
chemotherapy.
PMID- 26434879
TI - Ki-67 Labeling Indices in 'Classic' versus 'Blastoid' Mantle Cell Lymphomas-
Proposed Cutoff Values for Routine Diagnostic Workup.
AB - BACKGROUND: Mantle-cell lymphoma (MCL) is a unique entity of peripheral B-cell
lymphoma that has a discrete morphologic, immunologic, and genetic phenotype,
with more common 'classic' and less frequent 'blastoid' and 'pleomorphic'
variants, associated with an aggressive clinical course. The aim of this study
was to analyze proliferation (Ki-67) indices of 'classic' (c-MCL) and 'blastoid'
(b-MCL) variants of a cohort of MCL and to suggest cut off values for the Ki-67
proliferation index in these two subsets. MATERIALS AND METHODS: MCL cases
diagnosed over 4 1/2 years at Section of Histopathology, Department of Pathology
and Laboratory Medicine, Aga Khan University Hospital, Karachi were retrieved and
reviewed. Ki-67 labelling was scored and analysed. RESULTS: A total of 90 of
cases of MCL were scrutinized. Mean age+/-SD was 60.2+/-12.5 years and the male
to female ratio was 4:1, with 67 (75%) cases of c-MCL and 23 (25%) cases of b
MCL. Most samples were lymph node biopsies (n=68), whereas the remainder were
from various extranodal sites The mean Ki-67 proliferation index was 29.5%+/
14.4% in classic variants and 64.4+/-15.2% for the blastoid variant, the
difference being statistically significant (p=0.029). CONCLUSIONS: It was
concluded that differential cut-off values of Ki-67 labeling may be used in more
objective way to reliably classify MCL into classic or blastoid variants by
diagnostic pathologists. We propose a <40 proliferative index to be suggestive of
c-MCL and one of >50 for the blastoid variant.
PMID- 26434880
TI - Clinical Study on Lobaplatin Combined with 5-Fu and Concurrent Radiotherapy in
Treating Patients with Inoperable Esophageal Cancer.
AB - OBJECTIVE: To investigate short- and long-term treatment effects and side
reactions of lobaplatin plus 5-Fu combined and concurrent radiotherapy in
treating patients with inoperable middle-advanced stage esophageal cancer.
METHODS: Sixty patients with middle-advanced stage esophageal squamous cell
cancer were retrospectively analyzed. All patients were administered lobaplatin
(50 mg intravenously) for 2 h on day 1, and 5-Fu (500 mg/m2) injected
intravenously from day 1 to 5 for 1 cycle, in an interval of 21 days for totally
4 cycles. At the same time, late-course accelerated hyperfractionated three
dimensional conformal radiotherapy was performed. Patients were firstly treated
with conventional fractionated irradiation (1.8 Gy/d, 5 times/week, a total of 23
treatments, and DT41.4 Gy), and then treated with accelerated hyperfractionated
irradiation (1.5 Gy, 2 times/d, a total of 27 Gy in 9 days, an entire course of 6
7 weeks, and DT 68.4 Gy). RESULTS: All patients completed treatment, including 10
complete response (CR), 41 partial response (PR), 7 stable disease (SD), and 2
progressive disease (PD). The total effective rate was 85.0% (51/60). Thirty-nine
patients had an increased KPS score. One-, 2-, and 3-year survival rates were
85.3%, 57.5%, and 41.7%, respectively. The median survival time was 27 months.
The adverse reactions included myelosuppression, which was mainly degreeI and II.
The occurrence rate of radiation esophagitis was 17.5%. No significant hepatic or
renal toxicity was observed. CONCLUSION: Lobaplatin plus 5-Fu combined with
concurrent radiotherapy is safe and effective in treating patients with middle
advanced stage esophageal cancer. However, this result warrants further
evaluation by randomized clinical studies.
PMID- 26434881
TI - Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary
Cancer Screening.
AB - BACKGROUND: For the determination of creatine kinase (CK)-MB, the
immunoinhibition method is utilized most commonly. However, the estimated CK-MB
activity may be influenced by the presence of CK isoenzymes in some conditions
like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such
a situation. The study aimed to explore the relationship of cancer to high CK-MB
to-total-CK ratio. MATERIALS AND METHODS: From January 2011 to December 2014,
laboratory data on all CK-MB and total CK test requests were extracted at Far
Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK
ratio more than 1.0 were registered in this study. Clinical data including tumor
location, tumor TNM stage and metastatic status were also collected. RESULTS: A
total of 846 patients were identified with a CK-MB-to-total-CK ratio more than
1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to
total-CK ratio was significantly higher in malignancy than in non-malignancy
(1.35+/-0.28 vs 1.25+/-0.23, p<0.001) groups. The most frequent malignancy with a
CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer (1.42+/-0.28, 16.5%,
n=56), followed by lung cancer (1.38+/-0.24, 15.9%, n=54) and hepatocellular
carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological
malignancies (1.44+/-0.41)were also noted. Additionally, the CK-MB-to-total-CK
ratio was markedly higher in advanced stage malignancy than in early stage
(1.37+/-0.26 vs. 1.29+/-0.31, p=0.014) and significantly higher in liver
metastasis than in non-liver metastasis (1.48+/-0.30 vs. 1.30+/-0.21, p<0.001).
CONCLUSIONS: The CK-MB-to-total-CK ratio is an easily available indicator and
could be clinically utilized as a primary screening tool for cancer. Higher ratio
of CK-MB-to-total-CK was specifically associated with certain malignancies, like
colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some
cancer-associated status factors such as advanced stage and liver metastasis.
PMID- 26434882
TI - Information Engineering and Workflow Design in a Clinical Decision Support System
for Colorectal Cancer Screening in Iran.
AB - BACKGROUND: Colorectal cancer is a major cause of morbidity and mortality
throughout the world. Colorectal cancer screening is an optimal way for reducing
of morbidity and mortality and a clinical decision support system (CDSS) plays an
important role in predicting success of screening processes. DSS is a computer
based information system that improves the delivery of preventive care services.
The aim of this article was to detail engineering of information requirements and
work flow design of CDSS for a colorectal cancer screening program. MATERIALS AND
METHODS: In the first stage a screening minimum data set was determined.
Developed and developing countries were analyzed for identifying this data set.
Then information deficiencies and gaps were determined by check list. The second
stage was a qualitative survey with a semi-structured interview as the study
tool. A total of 15 users and stakeholders' perspectives about workflow of CDSS
were studied. Finally workflow of DSS of control program was designed by standard
clinical practice guidelines and perspectives. RESULTS: Screening minimum data
set of national colorectal cancer screening program was defined in five sections,
including colonoscopy data set, surgery, pathology, genetics and pedigree data
set. Deficiencies and information gaps were analyzed. Then we designed a work
process standard of screening. Finally workflow of DSS and entry stage were
determined. CONCLUSIONS: A CDSS facilitates complex decision making for screening
and has key roles in designing optimal interactions between colonoscopy,
pathology and laboratory departments. Also workflow analysis is useful to
identify data reconciliation strategies to address documentation gaps. Following
recommendations of CDSS should improve quality of colorectal cancer screening.
PMID- 26434883
TI - Expression of Matrix Metalloproteinase-10 at Invasive Front of Squamous Cell
Carcinoma and Verrucous Carcinoma in the Oral Cavity.
AB - BACKGROUND: Matrix metalloproteinases (MMPs) are a family of zinc
metalloproteinases capable of degrading components of connective tissues. MMP-10
is frequently expressed in human cancers. The aim of this study was to
immunohistochemically evaluate its expression in oral squamous cell carcinoma
(OSCC) and verrucous carcinoma (OVC). MATERIALS AND METHODS: A retrospective
analysis of 73 samples (31 OSCC, 22 OVC and 20 non-neoplastic epithelium) was
performed. All samples were immunohistochemically stained with monoclonal MMP-10
antibody and expression levels and staining intensity were evaluated with respect
to microscopic features. Data were analyzed by SPSS (V.21), Mann-Whitney and
Kruskal Wallis tests. RESULTS: MMP-10 was detected in all OSCC and OVC cases. The
expression of MMP-10 in OSCC was intensive (score 3) and in OVC was low and
moderate (score 1 and score 2) more frequently. Non- neoplastic epithelium did
not show MMP-10 expression. Differences between groups was statistically
significant (p<0.05). However, the expression of MMP- 10 was not obviously
different between various grades of OSCC. CONCLUSIONS: According to our study,
MMP-10 protein can be important possible factor in the transformation of normal
oral epithelium to OVC and OSCC, also the level of MMP-10 expression at invasion
front of the lesions can be helpful in the differentiation of OVC and OSCC.
PMID- 26434884
TI - Possible Role of HER-2 in the Progression of Prostate Cancer from Primary Tumor
to Androgen Independence.
AB - BACKGROUND: The expression of HER-2 in prostate cancer has been linked to disease
progression. We analysed the presence of HER-2 expression in primary tumors in
men undergoing radical prostatectomy, its association with clinical and
pathological findings, and its expression in secondary circulating prostate cells
(CPCs) during follow up, as well as links with biochemical failure and the
effects of androgen blockade. MATERIALS AND METHODS: Consecutive men undergoing
radical prostatectomy for histologically confirmed prostate cancer were analyzed.
HER-2 expression in the primary tumor was assessed using the HercepTest(r), CPCs
were identified from blood samples using standard immunocytochemistry with anti
PSA and positive samples with the HercepTest(r) to determine HER-2 expression.
The influence of HER-2 expression on the frequency of biochemical failure and
effects of androgen blockade was determined. RESULTS: 144 men with a mean age of
64.8+/-10.3 years participated, with a median follow up of 8.2 years. HER-2 was
expressed in 20.8% of primary tumors; it was associated with vascular
infiltration and older age, but not with other clinical pathological findings.
Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men
CPC (+) had a higher frequency of biochemical failure, but there was no
difference in HER-2 expression of CPCs with the frequency of biochemical failure.
After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher
frequency of disease progression to castrate resistant disease. CONCLUSIONS: HER
2 plays a dual role in the progression of prostate cancer; firstly it may
increase the potential of tumor cells to disseminate from the primary tumor via
the blood by increasing vascular infiltration. In the presence of androgens,
there is no survival advantage of expressing HER-2, but once biochemical failure
has occurred and androgen blockade started, HER-2 positive cells are resistant to
treatment, survive and grow leading to castration resistant disease.
PMID- 26434885
TI - Metformin Addition to Chemotherapy in Stage IV Non-Small Cell Lung Cancer: an
Open Label Randomized Controlled Study.
AB - PURPOSE: To evaluate effects of metformin on clinical outcome of non-diabetic
patients with stage IV NSCLC. MATERIALS AND METHODS: A prospective, randomized,
open-label, controlled pilot study was conducted on patients with stage IV NSCLC
with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2,
excluding patients with diabetes and lactic acidosis. Thirty chemo-naive, non
diabetic patients with stage IV NSCLC were enrolled. Fifteen patients received
intravenous gemcitabine/cisplatin regimen alone (arm B) while fifteen patients
received the same regimen plus daily oral metformin 500 mg (arm A). The effect of
metformin on chemotherapy-response rates, survival, and adverse events in these
patients was evaluated. RESULTS: Objective response rate (ORR) and median overall
survival (OS) in arms A and B were 46.7% versus 13.3% respectively, p=0.109 and
12 months versus 6.5 months, respectively, p=0.119. Median progression free
survival (PFS) in arms A and B was 5.5 months versus 5 months, p=0.062. No
significant increase in toxicity was observed in arm A versus arm B. Percentage
of patients who experienced nausea was significantly lower in arm A versus arm B,
at 26.7% versus 66.7% respectively, p=0.028. CONCLUSIONS: Metformin
administration reduced occurrence of chemotherapy induced-nausea. Non
statistically significant improvements in the ORR or OS were observed. Metformin
had no effect on PFS.
PMID- 26434886
TI - Decitabine in the Treatment of Acute Myeloid Leukemia and Myelodysplastic
Syndromes, Which Combined with Complex Karyotype Respectively.
AB - BACKGROUND: We conducted a study exploring the clinical safety and efficacy of
decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic
syndromes (MDS), combined with a complex karyotype. MATERIALS AND METHODS: From
April 2009 to September 2013, a total of 35 patients with AML/MDS combined with a
complex karyotype diagnosed in the First Affiliated Hospital of Soochow
University were included for retrospective analysis. All patients were treated
with decitabine alone (20 mg/m2 daily for 5 days) or combination AAG chemotherapy
(Acla 20 mg qod*4d, Ara-C 10 mg/m2 q12h*7d, G-CSF 300 MUg qd, the dose of G-CSF
adjusted to the amount in blood routinely). RESULTS: In 35 patients, 15 exhibited
a complete response (CR), and 6 a partial response (PR), the overall response
rate (CR+PR) being 60% (21 of 35). Median disease-free survival was 18 months and
overall survival was 14 months. In the 15 MDS patients with a complex karyotype,
the CR rate was 53.3% (8 of 15); in 20 AML patients with complex karyotype, the
overall response rate was 65% (13 of 20). The response rate of decitabine alone
(22 cases) was 56.5% (13 of 22), while in the combination chemotherapy group (13
cases), the effective rate was 61.5% (8 of 13)(P>0.05). There are 15 patients
with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR,
overall response rate was 66.7% (10 of 15). Of 18 patients with 3 to 5 kinds of
chromosomal abnormalities, 66.7% demonstrated a response; of 17 with more than 5
chromosomal abnormalities, 52.9% had a response. In the total of 35 patients,
with one course (23 patients) and >=two courses (12 patients), the overall
response rate was 40.9% and 92.3% (P<0.05). Grade III to IV hematological
toxicity was observed in 27 cases (75%). Grade III to IV infections were
clinically documented in 7 (20%). Grades I to II non-hematological toxicity were
infections (18 patients), haematuria (2 patients), and bleeding (3 patients).
With follow-up until September 2013, 7 patients were surviving, 18 had died and
10 were lost to follow-up. In the 6 cases who underwent allogeneic hematopoietic
stem cell transplantation (HSCT) all were still relapse-free survivors.
CONCLUSIONS: Decitabine alone or combination with AAG can improve outcome of
AML/MDS with a complex karyotype, there being no significant difference
decitabine in inducing remission rates in patients with different karyotype.
Increasing the number of courses can improve efficiency. This approach with fewer
treatment side effects in patients with a better tolerance should be employed in
order to create an improved subsequent chance for HSCT.
PMID- 26434887
TI - Lived Experience among Patients Newly Diagnosed with Lung Adenocarcinoma Stage IV
within One Year.
AB - BACKGROUND: lung cancer (LC) is the fifth of the 10 leading causes of death in
the world. LC is in first place for cancer-related mortality for both males and
females in Taiwan. It is one of the most difficult cancers to treat and is often
diagnosed at a late stage. Patients with stage IV are often unprepared for the
diagnosis. MATERIALS AND METHODS: To explore lived experience among patients
newly diagnosed with lung adenocarcinoma stage IV within one year. RESULTS:
Twelve participants were recruited in this study. Content analysis of the
interviews revealed four themes: (1) emotional roller coaster, (2) trying to find
out causes, (3) adjusting my lifestyle, and (4) cancer fighter. CONCLUSIONS: This
study provides new insight into the experiences of lung cancer patients y with
newly diagnosed lung adenocarcinoma stage 4. These results will inform future
supportive care service development and intervention research for patients with
advanced stage cancer.
PMID- 26434888
TI - Correlation between Microvascular Density and Matrix Metalloproteinase 11
Expression in Prostate Cancer Tissues: a Preliminary Study in Thailand.
AB - BACKGROUND: Prostate cancer is a major concern of public health. Microvascular
density (MVD) is one of the prognostic markers for various solid cancers. Matrix
metalloproteinase 11 (MMP11) plays an important role in angiogenesis and changes
in its expression level are known to be associated with tumor progression and
clinical outcome. AIM: To investigate the relationship between MVD and MMP11
expression in prostatic adenocarcinoma tissues. MATERIALS AND METHODS: The
expression levels of MMP11 and MVD were analyzed immunohistochemically for 50
specimens of prostatic adenocarcinoma. RESULTS: MMP11 was mainly expressed in
stromal cells but rarely seen in epithelial cells. Mean MVD was 36/mm2, and it
was correlated significantly only with bone metastases. MVD was also
significantly correlated with MMP11 expression (r=0.29, p=0.044). CONCLUSIONS:
MMP11 may alter the stromal microenvironment of prostate cancer to stimulate
tumor angiogenesis.
PMID- 26434889
TI - Helicobacter pylori cag Pathogenicity Island cagL and orf17 Genotypes Predict
Risk of Peptic Ulcerations but not Gastric Cancer in Iran.
AB - BACKGROUND: Gastric cancer (GC) is the third most common cancer regarding
mortality in the world. The cag pathogenicity island (PAI) of Helicobacter pylori
which contains genes associated with a more aggressive phenotype may involve in
the pathogenesis of gastrointestinal disease. We here aimed to examine the
associations of cagH, cagL, orf17, and cagG genotypes of H. pylori cag PAI with
severe gastrointestinal disease. MATERIALS AND METHODS: A total of 242 H. pylori
strains were genotyped. Histopathological examination and classification of
subjects were performed. RESULTS: The frequencies of the cagH, cagL, cagG, and
orf17 genotypes were 40/54 (74.1%), 53/54 (98.1%), 38/54 (70.4%), and 43/54
(79.6%), respectively, in patients with peptidic ulceration (PU),while in the
control group, the frequencies were 87/147 (59.6%) for cagH, 121/146 (82.9%) for
cagL, 109/146 (74.7%) for cagG, and 89/146 (61.0%) for orf17. The results of
simple logistic regression analysis showed that the cagL and orf17 genotypes were
significantly associated with an increased risk of PU not GC; the ORs (95% CI)
were 10.950 (1.446-82.935), and 2.504 (1.193-5.253), respectively. No significant
association was found between the cagH and cagG genotypes and the risk of both
the PU and the GC in Iran (P>0.05). Finally, multiple logistic regression
analysis showed that the cagL genotype was independently and significantly
associated with the age- and sex-adjusted risk for PU; the OR (95% CI) was 9.557
(1.219-17.185). CONCLUSIONS: We conclude that the orf17 and especially cagL
genotypes of H. pylori cag PAI could be factors for risk prediction of PU, but
not GC in Iran.
PMID- 26434890
TI - In Vitro Apoptosis Triggering in the BT-474 Human Breast Cancer Cell Line by
Lyophilised Camel's Milk.
AB - Breast cancer is a global health concern and is a major cause of death among
women. In Oman, it is the most common cancer in women, with an incidence rate of
15.6 per 100,000 Omani females. Various anticancer remedies have been discovered
from natural products in the past and the search is continuing for additional
examples. Cytotoxic natural compounds may have a major role in cancer therapy
either in potentiating the effect of chemotherapy or reducing its harmful
effects. Recently, a few studies have reported advantages of using crude camel
milk in treating some forms of cancer. However, no adequate data are available on
the lyophilised camel's milk responsibility for triggering apoptosis and
oxidative stress associated with human breast cancer. The present study aimed to
address the role of the lyophilised camel's milk in inducing proliferation
repression of BT-474 and HEp-2 cells compared with the non-cancer HCC1937 BL cell
line. Lyophilized camel's milk fundamentally repressed BT-474 cells growth and
proliferation through the initiation of either the intrinsic and extrinsic
apoptotic pathways as indicated by both caspase-3 mRNA and its action level, and
induction of death receptors in BT-474 but not the HEp-2 cell line. In addition,
lyophilised camel's milk enhanced the expression of oxidative stress markers,
heme-oxygenase-1 and reactive oxygen species production in BT-474 cells. Increase
in caspase-3 mRNA levels by the lyophilised camel's milk was completely prevented
by the actinomycin D, a transcriptional inhibitor. This suggests that lyophilized
camel's milk increased newly synthesized RNA. Interestingly,it significantly
(p<0.003) repressed the growth of HEp-2 cells and BT-474 cells after treatment
for 72 hours while 24 hours treatment repressed BT-474 cells alone. This finding
suggests that the lyophilised camel's milk might instigate apoptosis through
initiation of an alternative apoptotic pathway.
PMID- 26434891
TI - High Expression of Lung Resistance Protein mRNA at Diagnosis Predicts Poor Early
Response to Induction Chemotherapy in Childhood Acute Lymphoblastic Leukemia.
AB - BACKGROUND: Treatment failure in leukemia is due to either pharmacokinetic
resistance or cell resistance to drugs. MATERIALS AND METHODS: Gene expression of
multiple drug resistance protein (MDR-1), multidrug resistance-related protein
(MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and
7 healthy controls by real time PCR. The expression was scored as negative, weak,
moderate and strong. RESULTS: The male female ratio of cases was 2.75:1 and the
mean age was 5.2 years. Some 26/45 (58%) were in standard risk, 17/45(38%)
intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and
recurrent translocations being noted in 5/45 (11.0%). Rapid early response (RER)
at day 14 was seen in 37/45 (82.3%) and slow early response (SER) in 8/45 (17.7%)
cases. Positive expression of MDR-1, LRP and MRP was noted in 14/45 (31%), 15/45
(33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%)
and 8/15 (53.3%) cases respectively. Dual or more gene positivity was noted in
17/45 (38%) cases. 46.5 % (7/15) of LRP positive cases at day 14 were in RER as
compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%) LRP
positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3%
of LRP positive cases were in haematological remission at day 30 as compared to
100% of LRP negative cases (p=<0.05). CONCLUSIONS: Our study indicated that
increased LRP expression at diagnosis in pediatric ALL predicts poor response to
early treatment and hence can be used as a prognostic marker. However, larger
prospective studies with longer follow up are needed, to understand the clinical
relevance of drug resistance proteins.
PMID- 26434892
TI - Poor Knowledge and Practice Towards Breast Cancer among Women in Baghdad City,
Iraq.
AB - BACKGROUND: Breast cancer is one of the most common cancers among females
worldwide. The aim of this study was to assess the knowledge and practice about
breast cancer and its related factors among women in Baghdad city, Iraq.
MATERIALS AND METHODS: A cross-sectional study was conducted among 508 women aged
18 to 55 years from four non-governmental organizations (NGO) in Baghdad city,
Iraq. A self-administered questionnaire on breast cancer knowledge and practice
was distributed to participants during weekly activity of the NGO. RESULTS: A
total of 61.2% of the respondents had poor knowledge, only 30.3% performed breast
self-examination (BSE) and 41.8% said that they did not know the technique to
perform BSE. Associations between knowledge and marital status and age were
significant. For practice, working status, education, age and family income were
significant. After controlling for cofounders, the most important contributing
factors for poor knowledge among respondents were marital status and not
performing BSE, with adjusted odds ratio of 1.6 and 1.8 respectively.
CONCLUSIONS: Breast cancer knowledge and practice of BSE are poor among women in
Baghdad city, Iraq. More promotion regarding breast cancer signs and symptoms and
also how to perform BSE should be conducted using media such as television and
internet as these constituted the main sources of information for most women in
our study.
PMID- 26434893
TI - Male Breast Cancer: 20 Years Experience of a Tertiary Hospital from the Middle
Black Sea Region of Turkey.
AB - BACKGROUND: Male breast cancer is a rare neoplasm, and its treatments are based
on those of female breast cancer. This study aimed to analyze 20 years of male
breast cancer clinical characteristics and treatment results from the Middle
Black Sea Region of Turkey. MATERIALS AND METHODS: A retrospective analysis of 16
male breast cancer patients treated in our tertiary hospital between 1994 and
2014 was performed. Epidemiologic data, tumor characteristics, and treatments
were recorded and compared with 466 female breast cancer ((premenopausal;
n=230)+(postmenopausal n=236)) patients. The 5-year disease-free and overall
survival rates were calculated. RESULTS: Male breast cancer constituted 0.1% of
all malignant neoplasms in both sexes, 0.2% of all malignant neoplasms in males,
and 0.7% of all breast cancers. The mean patient age in this study was 59.8+/-9.5
(39-74) years. The mean time between first symptom and diagnosis was 32.4+/-5.3
(3-60) months. Histology revealed infiltrative ductal carcinoma in 81.3% of
patients. The most common detected molecular subtype was luminal A, in 12 (75%)
patients. Estrogen receptor rate (93.8%) in male breast cancer patients was
significantly higher than that in female breast cancer (70.8% in all females,
p=0.003; 68.2% in postmenopausal females, p=0.002) patients. Most of the tumors
(56.3%) were grade 2. Tumor stage was T4 in 50% of males. The majority (56.3%) of
the patients were stage III at diagnosis. Surgery, chemotherapy, radiotherapy and
endocrine-therapy were applied to 62.5%, 62.5%, 81.2% and 73.3%, respectively.
Loco-regional failure did not occur in any of the cases. All recurrences were
metastastic. The 5-year disease-free and overall survival rates in male breast
cancer patients were 58% and 68%, respectively. CONCLUSIONS: Tumors found in male
breast cancer patients were similar in size to tumors found in females, but they
advanced to T4 stage more rapidly because of the lack of breast parenchymal
tissues. The rate of estrogen receptor expression tended to be higher in male
breast cancer patients than in female breast cancer patients. Metastasis is the
most important problem in initially non-metastatic male breast cancer patients.
PMID- 26434894
TI - Tumors Involving Skin, Soft Tissue and Skeletal Muscle: Benign, Primary Malignant
or Metastatic?
AB - BACKGROUND: Metastatic cancer with invasion of skin, soft tissue and skeletal
muscle is not common. Examples presenting as soft tissue masses could sometimes
lead to misdiagnosis with delayed or inappropriate management. The purpose of
current study was to investigate clinical characteristics in the involvement of
metastatic cancer. MATERIALS AND METHODS: A total of 1,097 patients complaining
of skin or soft tissue masses and/or lesions were retrospectively reviewed from
January 2012 to June 2013. Tumors involving skin, soft tissue and skeletal muscle
of head and neck, chest wall, abdominal wall, pelvic region, back, upper and
lower extremities were included in the study. RESULTS: Fifty-seven (5.2%)
patients were recognized as having malignancies on histopathological examination.
The most common involvement of malignancy was basal cell carcinoma, followed by
cutaneous squamous cell carcinoma, sarcoma and melanoma. The most common
anatomical location in skin and soft tissue malignancies was head and neck (52.6%
of the malignancies). Four (0.36%) of the malignant group were identified as
metastatic cancer with the primary cancer source from lung, liver and tonsil and
the most common site was upper extremities. One of them unexpectedly expired
during the operation of metastatic tumor excision at the scalp. CONCLUSIONS:
Discrimination between benign and malignant soft tissue tumors is crucial.
Performance of imaging study could assist in the differential diagnosis and the
pre-operative risk evaluation of metastatic tumors involving skin, soft tissue
and skeletal muscle.
PMID- 26434895
TI - CHRNA5 rs16969968 Polymorphism Association with Risk of Lung Cancer--Evidence
from 17,962 Lung Cancer Cases and 77,216 Control Subjects.
AB - BACKGROUND: Genetic studies have shown a possible relationship between the
rs16969968 polymorphism in CHRNA5 and the risk of lung cancer. However, the
results have been conflicting. Thus we rigorously conducted a meta-analysis to
clarify any association. MATERIALS AND METHODS: A total of 10 case-control
studies involving 17,962 lung cancer cases and 77,216 control subjects were
analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to
measure the strength of the association. RESULTS: We found the CHRNA5 rs16969968
polymorphism to be associated with the risk of lung cancer (AA vs GG: OR=1.60,
95%CI=1.51-1.71). On stratified analysis by smoking status, a statistically
significant increased risk was observed in the smoking group (AA vs GG: OR=1.80,
95%CI=1.61-2.01). However, this polymorphism was not associated with lung cancer
risk in Asians (AA vs GG: OR=0.95, 95%CI=0.35-2.59), whereas it was linked to
increased risk of lung cancer among Caucasians (AA vs GG: OR=1.65, 95%CI=1.55
1.76). CONCLUSIONS: Our meta-analysis provided statistical evidence for a strong
association between rs16969968 polymorphism and the risk of lung cancer,
especially in smokers and Caucasians. Application of this relationship may
contribute to identification of individuals at high risk of lung cancer and
indicate a chemoprevention target.
PMID- 26434896
TI - Accuracy of Sentinel Node in Detecting Lymph Node Metastasis in Primary
Endometrial Carcinoma.
AB - BACKGROUND: Endometrial carcinoma is the most common gynecological cancer and its
treatment is still controversial, especially in its early stages. There are
conflicting data about the efficacy of retroperitoneal lymphadenectomy during
abdominal hysterectomy and bilateral salpingoophrectomy treatment.
Lymphadenectomy carries a risk of severe complications, especially in women with
co-morbidities. Selective lymphadenectomy has been widely employed for staging
evaluation of endometrial carcinoma because it is simple and seems to provide
reliable data regarding nodal metastasis. This study was designed to evaluate
accuracy of sentinel node sampling in detecting lymph node metastasis in primary
endometrial carcinoma during staging laparotomy. MATERIALS AND METHODS: Ninety
three women with endometrial carcinoma at high-risk for nodal metastasis were
studied. During laparotomy, methylene blue dye was injected into sub-serosal
myometrium, then retroperitoneal spaces were opened and blue lymph nodes within
pelvic and para-aortic regions were removed as separate specimens for
histopathological examination (sentinel lymph nodes=SLNs). Hysterectomy and
selective lymphadenectomy then performed for all women included in this study.
RESULTS: Deposition of methylene dye into at least one lymph node was observed in
73.1% (68/93) of studied cases. 18.3% (17/93) of studied women had positive lymph
node metastasis and 94.1% (16/17) of them had positive metastasis in SLNs. In
this study, SNLs had 94.4% sensitivity and 100% specificity in prediction of
lymph node metastasis. Mean number of lymph nodes removed from each case
decreased when SLNs biopsy were taken. CONCLUSIONS: SLNs are the key lymph nodes
in endometrial tumor metastasis and their involvement could be an indicator for
whether or not complete systematic lymphadenectomy is needed during staging
laparotomy.
PMID- 26434897
TI - Differences in Breast and Cervical Cancer Screening Rates in Jordan among Women
from Different Socioeconomic Strata: Analysis of the 2012 Population-Based
Household Survey.
AB - BACKGROUND: The burden of breast and cervical cancer is changing over time in
developing countries. Regular screening is very important for early detection and
treatment. In this study, we assessed inequalities in breast and cervical cancer
screening rates in women according to household wealth status, and analyzed the
potential predictors associated with a low cancer screening rate in Jordan.
MATERIALS AND METHODS: A nationwide population- based cross-sectional survey
collected information on different variables at the national level. All ever
married women (the phrase is used throughout the text to refer to women who had
ever married) aged 15-49 years were included in the survey. Analysis of breast
self-examination (BSE) and clinical breast examination (CBE) at least once in the
previous year was carried out in 11,068 women, while lifetime Pap-smear testing
was carried out in 8,333 women, aged 20-49 years. RESULTS: Over 39% and 19% of
ever-married Jordanian women reported having undergone a breast examination
during the previous year and Pap smear examination at least once in their
lifetime, respectively. The rate of BSE in the previous year was 31.5%, that of
CBE in the previous year was 19.3%, and that of Pap smear examination at least
once in life was 25.5%. The adjusted OR was higher for performing BSE (aOR 1.22,
95% CI 1.04-1.43), undergoing CBE (aOR 1.31, 95% CI 1.08-1.60) and undergoing Pap
smear examination (aOR 2.38, 95% CI 1.92-2.93) among women in the highest wealth
index quintile as compared to those in the lowest quintile. The concentration
index was 0.11 for BSE, 0.01 for CBE, and 0.27 for Pap smear examination. Women
in their twenties, living in rural or the southern region of Jordan, with an
elementary school education or less, who listened to the radio or read the
newspaper not more than a few times a year, and nulliparous women were less
likely to undergo breast and cervical cancer screening. CONCLUSIONS: The rates of
breast and cervical cancer screening are low in Jordan. Reducing the
sociodemographic and economic inequalities in breast and cervical cancer
screenings requires concerted outreach activities for women living under socially
deprived conditions.
PMID- 26434898
TI - Incidence and Clinical Characteristic of Venous Thromboembolism in Gynecologic
Oncology Patients attending King Chulalongkorn Memorial Hospital over a 10 Year
Period.
AB - BACKGROUND: Venous thromboembolisms (VTEs) constitute a group of diseases
including deep vein thrombosis (DVT) and pulmonary embolism (PE). They regarded
as the second leading cause of death in cancer patients and several studies have
confirmed that VTEs have a negative impact on survival and recurrent rate in both
ovarian and endometrial cancer cases. The incidence of VTEs differs worldwide and
depends on several risk factors including race, underlying disease, lifestyle,
body weight, BMI and genetic risk factors. There is heterogeneity of DVT rates
between Asian and Western countries. This study was conducted in order to
evaluate the character and incidence of VTEs in gynecologic oncology patients in
King Chulalongkorn Memorial Hospital over a 10 year period. MATERIALS AND
METHODS: A retrospective chart review was performed with VTEs defined as
objective diagnosis of acute DVT or PE with typical symptoms and signs. Diagnoses
were approved byan internist and/ or confirmed with imaging studies. Data from
both outpatient and inpatient sessions of the affected cases from January 2004 to
December 2013 were extracted. General characteristics of the patients were
collected with details of the diseases, types of cancer, stage, date of diagnosis
of cancer, operative data, treatment outcome, progression free survival and
overall survival. RESULTS: Thirty cases of VTEs were identified in a total 2,316
gynecologic oncology cases. The incidence of symptomatic VTEs in total
gynecologic oncology patients in our institution is 1.295%. The incidence of VTEs
in ovarian cancer patients in our institution was 5.9%. Duration for VTE
detection ranged from 13 months before diagnosis of cancer to 33 months after
diagnosis of cancer. Most of the VTE cases were detected in ovarian cancer
patients (60%). The most common cell type was adenocarcinoma (moderately to
poorly differentiated) which accounted for 26.7% of the cases. The second most
common cell type was clear cell carcinoma with 23.3% of the cases. Thirty percent
of VTE cases developed before cancer was diagnosed, 20% were diagnosed at the
same time as cancer detection and fifty percent developed after cancer was
diagnosed. Median disease free survival of the gynecologic oncology patients with
VTE was 7.5 months. Median overall survival (OS) was 12 months. Median progession
free survivals of DVT and PE groups were 11.5 and 5.5 months, respectively. OS of
DVT and PE was 12.0 and 11.5 months respectively. CONCLUSIONS: The incidence of
VTE in Asian countries is believed to be lower than in European or Western
countries. From our retrospective review, the incidence of VTEs in all types of
gynecologic oncology was 1.295%, much lower than reported in the West. The reason
for the lower incidence may genetic differences. Another factor is that VTE in
this review was symptomatic, which is less than asymptomatic VTE. More than half
of VTEs in this study developed in ovarian cancer patients. The results are
compatible with earlier reports that among gynecologic malignancies, the
incidence of VTE is highest in ovarian cancer.
PMID- 26434899
TI - Insomnia in Cancer--Associations and Implications.
AB - BACKGROUND: Insomnia is a common condition in cancer patients. In spite of the
high prevalence its associations have not been well studied. Existing data
suggests that insomnia is related to depression and pain. However, the impact of
ongoing chemotherapy on sleep is not investigated. AIM: To study the relationship
between insomnia and chemotherapy after analysing confounding variables.
MATERIALS AND METHODS: Consecutive patients who visited New England Oncology
Clinic in Tamworth were recruited. Insomnia was assessed with the Bergen insomnia
scale. The Montgomery Asberg Depression rating scale was used to measure
depression. Pain was assessed with the Brief Pain inventory. Chronic medical
conditions, type of cancer, side effects to chemotherapy, role of steroids and
other drugs were studied as confounders. RESULTS: A total of 56 patients
participated in the study. Age ranged from 33 to 83 years (mean: 63.6, SD=10.97).
There were 29 men and 27 women. 42 patients received at least one form of
chemotherapy and 15 were receiving radiotherapy at the time of assessment. Mean
insomnia score was significantly higher in those receiving chemotherapy than in
those without chemotherapy (8.92 vs 17.2, two tailed p=0.005, 95% CI=2.63-13.71).
There was no significant variation in insomnia scores in terms of chronic medical
condition, type of cancer, psychiatric history, use of steroids or adverse
effects of chemotherapy. However, total insomnia score was correlated with
depression rating score (Pearson correlation, r=0.39, p=0.003) and magnitude of
pain (r=0.37, p=0.006). On regression analysis only pain was found to be
predictive of insomnia. CONCLUSIONS: Insomnia in patients with cancer is found to
be associated with concurrent chemotherapy and correlated with degree of
depression and pain. Identifying factors related to insomnia in cancer population
has implications in its management and patient education.
PMID- 26434900
TI - Descriptive Epidemiology of Thyroid Cancers in Togo.
AB - BACKGROUND: The purpose of this study was to provide epidemiological and
histological data of thyroid cancers in Togo. MATERIALS AND METHODS: This was a
retrospective cross-sectional study of cases of thyroid cancers diagnosed from
2000 to 2014 (15 years) at the pathology laboratory of the Sylvanus Olympio
Teaching Hospital of Lome. All cases of review of a thyroid sample (biopsies,
surgical specimens) were collected from the data records of that laboratory.
RESULTS: Thyroid cancers represented 1.1% (7930 cases) of all cancers registered
during the study period. Mean age was 45.4+/-0.3 years and the proportion of
females was 78.3%. We identified 92.4% carcinomas and 7.6% lymphomas. Carcinomas
were well differentiated in 80 cases and were dominated by the papillary type (47
cases). Metastasis was observed in 13% of patients. The pTNM classification
evaluated in 18 cases showed a predominance of grade I (13 cases). Lymphomas were
dominated by lymphoma diffuse large B-cell (5 cases). CONCLUSIONS: This study is
the first global standard for thyroid cancer pathology in Togo. The high
frequency of follicular form suggests an unrecognized iodine deficiency. The
improvement of the technical platform of the LAP (immunohistochemistry) will
increase the diagnosis of rare forms of thyroid cancer.
PMID- 26434901
TI - Readability, Suitability and Health Content Assessment of Cancer Screening
Announcements in Municipal Newspapers in Japan.
AB - BACKGROUND: The objective of this study was to assess the readability,
suitability, and health content of cancer screening information in municipal
newspapers in Japan. MATERIALS AND METHODS: Suitability Assessment of Materials
(SAM) and the framework of Health Belief Model (HBM) were used for assessment of
municipal newspapers that were published in central Tokyo (23 wards) from January
to December 2013. RESULTS: The mean domain SAM scores of content, literacy
demand, and layout/typography were considered superior. The SAM scores of
interaction with readers, an indication of the models of desirable actions, and
elaboration to enhance readers' self-efficacy were low. According to the HBM
coding, messages of medical/clinical severity, of social severity, of social
benefits, and of barriers of fear were scarce. CONCLUSIONS: The articles were
generally well written and suitable. However, learning stimulation/motivation was
scarce and the HBM constructs were not fully addressed. PRACTICE IMPLICATIONS:
Articles can be improved to motivate readers to obtain cancer screening by
increasing interaction with readers, introducing models of desirable actions and
devices to raise readers' self-efficacy, and providing statements of perceived
barriers of fear for pain and time constraints, perceived severity, and social
benefits and losses.
PMID- 26434902
TI - Mortality Characteristic and Prediction of Nasopharyngeal Carcinoma in China from
1991 to 2013.
AB - BACKGROUND: To analyze the mortality distribution of nasopharyngeal carcinoma in
China from 1991 to 2013, to predict the mortality in the ensuing five years, and
to provide evidence for prevention and treatment of nasopharyngeal carcinoma.
MATERIALS AND METHODS: Mortality data for Nasopharyngeal Carcinoma in China from
1991 to 2013 were used to describe its epidemiological characteristics, such as
the change of the standardized mortality rate, sex and age differences, urban
rural differences. Trend-surface analysis was used to study the geographical
distribution of the mortality. Curve estimation, time series, gray modeling, and
joinpoint regression were used to predict the mortality for the ensuing five
years in the future. RESULTS: In China, the standardized mortality rate of
Nasopharyngeal Carcinoma increased with time from 1996, reaching the peak values
of 1.45 /105 at the year of 2002, and decreased gradually afterwards. With males
being 1.51 times higher than females, and the city had a higher rate than the
rural during the past two decades. The mortality rate increased from age 40.
Geographical analysis showed the mortality rate increased from middle to southern
China. CONCLUSIONS: The standardized mortality rate of Nasopharyngeal Carcinoma
is falling. The regional disease control for Nasopharyngeal Carcinoma should be
focused on Guangdong province of China, and the key targets for prevention and
treatment are rural men, especially after the age of 40. The mortality of
Nasopharyngeal Carcinoma will decrease in the next five years.
PMID- 26434903
TI - Breast Cancer in Surat Thani, a Province in Southern Thailand: Analysis of 2004
2012 Incidence and Future Trends.
AB - BACKGROUND: With the recent epidemiologic transition in Thailand, featuring
decreasing incidences of infectious diseases along with increasing rates of
chronic conditions, cancer is becoming a serious problem for the country. Breast
cancer has the highest incidence rates among females, not only in the southern
regions, but throughout Thailand. Surat Thani is a province in the upper part of
Southern Thailand. A study was needed to identify the current burden, and the
future trends of breast cancer. MATERIALS AND METHODS: Here we used cancer
incidence data from the Surat Thani Cancer Registry to characterize the
incidences of breast cancer. Joinpoint analysis was used to investigate the
incidences in the province from 2004 to 2012 and to project future trends from
2013 to 2030. RESULTS: Age-standardized incidence rates (world) of breast cancer
in the upper parts of Southern Thailand increased from 35.1 to 59.2 cases per
100,000 female population, which is equivalent to an annual percentage change of
4.5-4.8%. Linear drift effects played a role in shaping the increase of
incidence. Joinpoint projection suggested that incidence rates would continue to
increase in the future with incidence for women aged 50 and above, at a higher
rate than for women below the age of 50. CONCLUSIONS: The current early detection
measures increase detection rates of early disease. Preparation of a budget for
treatment facilities and human resources, both in surgical and medical oncology,
is essential.
PMID- 26434904
TI - Intention to Quit Smoking among Intermediate and Secondary School Students in
Saudi Arabia.
AB - BACKGROUND: Smoking is one of the most preventable causes of disease and death,
including cancer, and quitting at an early age can reduce smoking-related
morbidity and mortality. This study aimed to estimate the prevalence and to
identify factors affecting the "intention to quit" among intermediate and
secondary school current cigarette smoker students in Al Madinah city, Saudi
Arabia. MATERIALS AND METHODS: This study cohort included 307 current smoker
students in a school-based survey. The intention to quit and its related
determinants were assessed using a self-administered questionnaire. RESULTS: More
than half of the participants were >=17 years, and of male gender (54.7%, 77.9%
respectively). An intention to quit smoking was reported in 71.7% of
participants, and was been significantly associated with: male gender (OR=3.25,
95% CI=1.65-6.41): age at 1st trial of smoking. 10-15 years (OR=2.11, 95% CI=1.03
4.32) along with age of >=15 years (OR=3.10, 95% CI=1.20-7.88); days of smoking
in the past 30 days (days<10 (OR=2.31, 95% CI=1.23-4.35) along with days ranging
from 10-19 days (OR= 3.42, 95% CI=1.18-9.91); knowing that smoking is hazardous
to health (OR=3.04, 95% CI=1.42-6.47); and finally, supporting smoking bans in
public places (OR=1.89, 95% CI=1.11-3.25). CONCLUSIONS: A substantial number of
participants were willing to quit smoking. Effective interventions focusing on
providing information about the hazards of smoking and prohibiting smoking in
public places could help initiate the intention to quit among youth smokers.
PMID- 26434905
TI - Serum Level of Matrix Metalloproteinase-2 and -9 in Patients with Laryngeal
Squamous Cell Carcinoma and Clinical Significance.
AB - BACKGROUND: Laryngeal cancer is an important malignancy in head and neck area and
squamous cell carcinoma (SCC) is the most common type accounting for 95% of
cases. Increase in matrix metalloproteinases (MMPs) in different tumors and their
correlation with tumor invasiveness has been documented. However, most studies
have evaluated MMP-2 and MMP-9 expression and few have evaluated serum levels.
The aim of current study was to evaluate serum levels in patients with laryngeal
SCC compared to normal subjects and assess any relation with tumor
clinicopathological findings. MATERIALS AND METHODS: In this case control study,
20 patients with oral SCC and 20 healthy subjects were included. Serum levels of
MMP-2 and MMP-9 were compared between groups and correlations with findings
including grade (T) and node involvement (N) were evaluated. RESULTS: Patients
with laryngeal SCC had significantly higher serum levels of MMP-2 (p=0.01) and
MMP-9 (p=0.03) compared to healthy subjects. Patients with higher T stage (T3,4)
had significantly higher MMP-2 (p=0.04) and MMP-9 (p=0.01). There was significant
positive correlation between serum levels of MMP-2 with T stage (r=0.45, p=0.04)
and lymph node involvement (r=0.563, p=0.01) and between levels of MMP-9 with T
stage (r=0.527, p=0.01). CONCLUSIONS: Our results showed that compared to healthy
subjects, both MMP-2 and MMP-9 are significantly increased in serum of laryngeal
SCC cases. MMP-2 was correlated with lymph node involvement while MMP-9 has
stronger correlation with T stage compared to MMP-2.
PMID- 26434906
TI - Induction of Apoptosis by Eugenol and Capsaicin in Human Gastric Cancer AGS Cells
-Elucidating the Role of p53.
AB - BACKGROUND: Loss of function of the p53 gene is implicated in defective apoptotic
responses of tumors to chemotherapy. Although the pro-apoptotic roles of eugenol
and capsaicin have been amply reported, their dependence on p53 for apoptosis
induction in gastric cancer cells is not well elucidated. The aim of the study
was to elucidate the role of p53 in the induction of apoptosis by eugenol and
capsaicin in a human gastric cancer cell line, AGS. MATERIALS AND METHODS: AGS
cells were incubated with or without various concentrations of capsaicin and
eugenol for 12 hrs, in the presence and absence of p53 siRNA. Cell cycling,
annexin V and expression of apoptosis related proteins Bax, Bcl-2 ratio, p21, cyt
c-caspase-9 association, caspase-3 and caspase-8 were studied. RESULTS: In the
presence of p53, capsaicin was a more potent pro-apoptotic agent than eugenol.
However, silencing of p53 significantly abrogated apoptosis induced by capsaicin
but not that by eugenol. Western blot analysis of pro-apoptotic markers revealed
that as opposed to capsaicin, eugenol could induce caspase-8 and caspase-3 even
in the absence of p53. CONCLUSIONS: Unlike capsaicin, eugenol could induce
apoptosis both in presence and absence of functional p53. Agents which can induce
apoptosis irrespective of the cellular p53 status have immense scope for
development as potential anticancer agents.
PMID- 26434907
TI - Repairing Facial Soft Tissue Defects by Swelling Anesthesia after Tumor Resection
with Narrow Pedicle Flaps.
AB - AIMS: To investigate the role of swelling anesthesia in repairing facial soft
tissue defects after tumor resection and temporal superficial artery frontal
branch of narrow pedicle flap. MATERIALS AND METHODS: From January 2008 to June
2008, 16 patients from Department of Ophthalmology with eye or eyelid tumors
after eyeball removal of eye and part resection of surrounding soft tissue,
undergoing postoperative swelling anesthesia with superficial temporal artery
flap repair to prevent facial soft tissue defect formation and bone exposure,
were recruited. RESULTS: In all 16 patients facial soft tissue defect repair had
good effects, with limited bleeding, and short operation times. Seven days after
surgery, all flaps were in good repair. On postoperative follow-up after 3
months, flaps showed a similar appearance as with facial tissue. CONCLUSIONS:
Swelling anesthesia for superficial temporoparietal artery frontal branch of
narrow pedicle flap to repair soft tissue defect after facial tumor resection is
feasible, and is linked with good analgesic effects, high postoperative survival
of skin flaps, and good cosmetic effects.
PMID- 26434908
TI - Human Recombinant Endostatin Combined with Cisplatin Based Doublets in Treating
Patients with Advanced NSCLC and Evaluation by CT Perfusion Imaging.
AB - AIMS: To study the effectiveness of human recombinant endostatin injection
(Endostar(r)) combined with cisplatin doublets in treating advanced non-small
cell lung cancer (NSCLC), and to evaluate outcome by CT perfusion imaging.
METHODS: From April 2011 to September 2014, 76 patients with advanced NSCLC who
were treated with platinum-based doublets were divided into group A (36 patients)
and group B (40 patients). Endostar(r) 15 mg/day was administered 4 days before
chemotherapy and combined with chemotherapy from day 5 in group A, and combined
with chemotherapy from the first day in Group B. Endostar(r) in the two groups
was injected intravenously for 14 days. RESULTS: Treatment effectiveness in the
two groups differed with statistical significance (p<0.05). Effectiveness
evaluated by CT perfusion imaging, BF, BV, MTT and PS also demonstrated
significant differences (all p<0.05). Adverse reactions in the two groups did not
significantly vary (p>0.05). CONCLUSIONS: The response rate with Endostar(r)
administered 4 days before chemotherapy and combined with chemotherapy from day 5
in group A was better than Endostar(r) combined with chemotherapy from the first
day, and CT perfusion imaging could be a reasonable method for evaluation of
patient outcomes.
PMID- 26434909
TI - Type-Specific Human Papillomavirus Distribution in Invasive Squamous Cervical
Carcinomas in Tunisia and Vaccine Impact.
AB - BACKGROUND: High risk human papillomaviruses (HPVs) are the leading cause of
cervical cancer (CC) and Pap smear screening has not been successful in
preventing CC in Tunisia. HPV vaccination that targets HPV16 and 18 offers a new
efficient prevention tool. Identification of HPV types in CC is thus essential to
determine the impact of HPV vaccine implementation. The aim of this study is to
provide specific data from Tunisia. MATERIALS AND METHODS: A total of 89
histological confirmed paraffin embedded samples isolated from patients with CC
diagnosed between 2001 and 2011 were collected from five medical centres from
Northern and Southern Tunisia. HPV DNA was detected using a nested PCR (MY09/MY11
GP5+/GP6+) and genotyping was assessed using a reverse blot line hybridisation
assay that enables the detection of 32 HPV types. RESULTS: HPV DNA was detected
in all samples. Twelve high risk types were detected; HPV16 and/or 18 were
predominant, accounting together for 92.1% of all the CC cases (HPV16: 83.1%).
Single infections accounted for 48.8% of the cases and were mostly linked to HPV
16 (32.6%) and less frequently to HPV 18 (2.4%). The other high risk HPV single
infections were linked to HPV 35 (4.6%), 45 (4.6%), 58 (2.3%) and 59 (2.3%).
Multiple infections with mixing of 2 to 4 genotypes predominately featrued HPV16
and/or 18 with HPV 35 and 45 (96.6 %) and less frequently with HPV 59, 40, 66, 73
and 58. There was no statistically significant variation in the relative
distribution of HPV types with age. CONCLUSIONS: These results strongly indicate
that prophylactic HPV vaccines can have a major impact in preventing CC in
Tunisia.
PMID- 26434910
TI - Survival Prognostic Factors of Male Breast Cancer in Southern Iran: a LASSO-Cox
Regression Approach.
AB - We used to LASSO-Cox method for determining prognostic factors of male breast
cancer survival and showed the superiority of this method compared to Cox
proportional hazard model in low sample size setting. In order to identify and
estimate exactly the relative hazard of the most important factors effective for
the survival duration of male breast cancer, the LASSO-Cox method has been used.
Our data includes the information of male breast cancer patients in Fars
province, south of Iran, from 1989 to 2008. Cox proportional hazard and LASSO-Cox
models were fitted for 20 classified variables. To reduce the impact of missing
data, the multiple imputation method was used 20 times through the Markov chain
Mont Carlo method and the results were combined with Rubin's rules. In 50
patients, the age at diagnosis was 59.6 (SD=12.8) years with a minimum of 34 and
maximum of 84 years and the mean of survival time was 62 months. Three, 5 and 10
year survival were 92%, 77% and 26%, respectively. Using the LASSO-Cox method led
to eliminating 8 low effect variables and also decreased the standard error by
2.5 to 7 times. The relative efficiency of LASSO-Cox method compared with the Cox
proportional hazard method was calculated as 22.39. The19 years follow of male
breast cancer patients show that the age, having a history of alcohol use, nipple
discharge, laterality, histological grade and duration of symptoms were the most
important variables that have played an effective role in the patient's survival.
In such situations, estimating the coefficients by LASSO-Cox method will be more
efficient than the Cox's proportional hazard method.
PMID- 26434911
TI - Effects of Definitive Chemoradiotherapy on Respiratory Function Tests and Quality
of Life Scores During Treatment of Lung Cancer.
AB - BACKGROUND: Chemoradiotherapy is an important treatment modality for lung
cancers. The aim of this study was to investigate alterations in, as well as the
interrelationship between, lung function and quality of life of patients
receiving chemoradiotherapy due to locally advanced non-small cell lung cancer
(NSCLC) and small cell lung cancer (SCLC) limited to the thorax. MATERIALS AND
METHODS: The study included patients receiving definitive chemoradiotherapy for
lung carcinoma. The respiratory function of the patients was assessed by
measuring forced expiratory volume in 1 s per unit (FEV1) and forced expiratory
volume in 1s per unit of vital capacity (FEV1/VC) before, in the middle of and
after treatment. During the study, EORTC QLQ C30 and LC13 questionnaires
developed by the Committee of the European Organization for Research and
Treatment of Cancer (EORTC) were employed to evaluate the quality of life on the
same day as respiratory function tests (RFT). FINDINGS: The study included 23
patients in total: 19 (82.6%) diagnosed with NSCLC and 4 (17.4%) with SCLC. The
average percentage FEV1 was 55.6+/-21.8% in the pre-treatment period, 56.2+/
19.2% in the middle of treatment and 60.4+/-22% at the end of treatment. The
improvement in functional scores, symptom scores and general health scores during
treatment was not statistically significant (P=0.568, P=0.734, P=0.680, P=0.757
respectively). CONCLUSIONS: Although this study showed an improvement in
respiratory function and quality of life of patients during treatment with
thoracic chemoradiotherapy, no statistically significant results were obtained.
While evaluating the effectiveness of treatments for lung carcinoma, the effects
of treatment on respiratory function and quality of life should be considered.
PMID- 26434912
TI - CYP2D6 Genotype and Risk of Recurrence in Tamoxifen Treated Breast Cancer
Patients.
AB - BACKGROUND: Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen
exposure, there is considerable controversy regarding the validity of CYP2D6 as a
predictor of tamoxifen outcome. Understanding the current state of evidence in
this area and its limitations is important for the care of patients who require
endocrine therapy for breast cancer. MATERIALS AND METHODS: A total of 101
patients with breast cancer who received tamoxifen therapy for at least 3 years,
were genotyped for common alleles of the CYP2D6 gene by nested-PCR and
restriction fragment length polymorphism PCR. Patients were classified as
extensive or poor metabolizers (PM) based on CYP2D6*4 alleles in 3 different
groups according to the menopause, Her2-neu status, and stage 3. RESULTS: The
mean age of the patients with the disease recurrence was 50.8+/-6.4 and in non
recurrent patients was 48.2+/-6.8. In this study 63.3% (n=64) patients were
extensive metabolizers and 36.6% (n=37) were poor metabolizers. Sixty four of the
101 patients (63.3%) were Her2-neu positive. For tamoxifen- treated patients, no
statistically significant difference in rate of recurrence observed between
CYP2D6 metabolic variants in stage 3 and post-menopausal patients. However, there
was a significant association between CYP2D6 genotype and recurrence in tamoxifen
treated Her2-neu positive patients. Compared with other women with breast cancer,
those with Her2-neu positive breast cancer and extensive metabolizer alleles had
a decreased likelihood of recurrence. CONCLUSIONS: This study for the first time
demonstrated significant effects of CYP2D6 extensive metabolizer alleles on risk
of recurrence in Her2-neu positive breast cancer patients receiving adjuvant
tamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic
variation, can be a predictor of breast cancer outcome in Her2-neu positive women
receiving tamoxifen.
PMID- 26434913
TI - Expression of ER, PR, C-erbB-2 and Ki-67 in Endometrial Carcinoma and their
Relationships with the Clinicopathological Features.
AB - BACKGROUND: To analyze the expression of estrogen receptors (ER), progesterone
receptors (PR), C-erbB-2 and Ki-67 in endometrial carcinoma (EC) and their
relationships with the clinicopathological features. MATERIALS AND METHODS: Sixty
seven EC samples, 53 normal endometrial samples and 53 atypical hyperplasia
endometrial samples were all selected in Shaanxi Provincial People's Hospital
from Jun., 2012 to Jun., 2014. The expression of ER, PR, C-erbB-2 and Ki-67 in EC
tissue, normal endometrial tissue and atypical hyperplasia endometrial tissue was
respectively detected using immunohistochemical SP method. The relationships
between the expression of ER, PR, C-erbB-2 and Ki-67 and the patients'
clinicopathological features as well as their correlations in EC tissue were also
analyzed. RESULTS: The positive expression rates of ER and PR in EC tissue were
44.8% and 41.8%, respectively, dramatically lower than in atypical hyperplasia
endometrial tissue and normal endometrial tissue (P<0.01). The positive
expression rates of C-erbB-2 and Ki-67 in EC tissue were 80.6% and 64.2%,
respectively, significantly higher than in atypical hyperplasia endometrial
tissue and normal endometrial tissue (P<0.01). In EC tissue, the expression of ER
and PR was closely associated with the differentiated degrees and depth of
myometrial invasion (P<0.05), while that of C-erbB-2 and Ki-67 with the clinical
staging, differentiated degrees, depth of myometrial invasion and presence or
absence of lymph node metastasis (P<0.05). Spearman correlation analysis further
displayed that the expression of ER was positively correlated with PR (r=0.393,
P=0.001), but negatively with C-erbB-2 and Ki-67 (r=-0.469, P=0.000; r=-0.329,
P=0.007); The expression of PR was negatively correlated with C-erbB-2 and Ki-67
(r=-0.273, P=0.025; r=-0.251, P=0.041), but that of C-erbB-2 positively with Ki
67 (r=0.342, P=0.005). CONCLUSIONS: Abnormal expression of ER, PR, C-erbB2 and Ki
67 might play an important role in endometrial malignant transformation and cell
differentiation, so their joint detection is likely to be a comprehensive
combination of immune factors, which is of great importance for EC prognosis.
PMID- 26434914
TI - Spatial and Temporal Epidemiological Assessment of Breast Cancer Incidence and
Mortality in Kazakhstan, 1999-2013.
AB - Breast cancer incidence and mortality in Kazakhstan are considered to be
increasing but exact statistics have hitherto been lacking. The present study was
therefore undertaken to retrospectively assess data for the whole country,
accessed from the central registration office, for the period 1999-2013. Age
standardized data for incidence and mortality were generated and compared across
age groups. It was determined that during the studied period 45,891 new cases of
breast cancer were registered and 20,122 women died of this pathology. Average
breast cancer incidence and mortality were 37.9+/-1.10/105 and 16.7+/-0.20/105
respectively, and the overall ratio of mortality/incidence (M/I) was 0.44.
Incidence tended to increase (T=+2.3%), and mortality to decrease (T of =-0.3%).
Peaks of incidence and mortality were noted in those aged 60-74 years and 75-84,
respectively. Particularly high incidences were established in large cities of
Kazakhstan, Astana (46.8+/-1.80/105) and Almaty (49.7+/-1.30/105), and high
mortality was observed in the Pavlodar region (17.9+/-0.60/105) and Almaty city
(20.1+/-0.40/105). Considerable variation in the mortality/incidence ratio was
noted, suggesting the need for more stress on access to screening and clinical
care in some regions of the country.
PMID- 26434915
TI - Cancer Patients, Complementary Medicine and Unmet Needs in Saudi Arabia.
PMID- 26434916
TI - A luminescent dye@MOF as a dual-emitting platform for sensing explosives.
AB - An anionic metal-organic framework (MOF) with 1D nanotube channels has been
constructed. The charge and size dependent ion-exchange of cationic dyes was
investigated. Rho@1 could be used as a dual-emitting fluorescent sensor for
sensing explosives by self-referencing energy transfer behaviors.
PMID- 26434917
TI - The IMD innate immunity pathway of Drosophila influences somatic sex
determination via regulation of the Doa locus.
AB - The IMD pathway induces the innate immune response to infection by gram-negative
bacteria. We demonstrate strong female-to-male sex transformations in double
mutants of the IMD pathway in combination with Doa alleles. Doa encodes a protein
kinase playing a central role in somatic sex determination through its regulation
of alternative splicing of dsx transcripts. Transcripts encoding two specific Doa
isoforms are reduced in Rel null mutant females, supporting our genetic
observations. A role for the IMD pathway in somatic sex determination is further
supported by the induction of female-to-male sex transformations by Dredd
mutations in sensitized genetic backgrounds. In contrast, mutations in either
dorsal or Dif, the two other NF-kappaB paralogues of Drosophila, display no
effects on sex determination, demonstrating the specificity of IMD signaling. Our
results reveal a novel role for the innate immune IMD signaling pathway in the
regulation of somatic sex determination in addition to its role in response to
microbial infection, demonstrating its effects on alternative splicing through
induction of a crucial protein kinase.
PMID- 26434919
TI - Single-molecule interfacial electron transfer dynamics of porphyrin on TiO2
nanoparticles: dissecting the interfacial electric field and electron accepting
state density dependent dynamics.
AB - Single-molecule photon-stamping spectroscopy correlated with electrochemical
techniques was used to dissect complex interfacial electron transfer (ET)
dynamics by probing an m-ZnTCPP molecule anchored to a TiO2 NP surface while
electrochemically controlling the energetically-accessible surface states of TiO2
NPs. Application of negative potential increases the electron density in TiO2
NPs, resulting in hindered forward ET and enhanced backward ET due to the changes
in the interfacial electric field and the occupancy of acceptor states.
PMID- 26434918
TI - Fibronectin signals through integrin alpha5beta1 to regulate cardiovascular
development in a cell type-specific manner.
AB - Fibronectin (Fn1) is an evolutionarily conserved extracellular matrix
glycoprotein essential for embryonic development. Global deletion of Fn1 leads to
mid-gestation lethality from cardiovascular defects. However, severe
morphogenetic defects that occur early in embryogenesis in these embryos
precluded assigning a direct role for Fn1 in cardiovascular development. We
noticed that Fn1 is expressed in strikingly non-uniform patterns during mouse
embryogenesis, and that its expression is particularly enriched in the pharyngeal
region corresponding with the pharyngeal arches 3, 4, and 6. This region bears a
special importance for the developing cardiovascular system, and we hypothesized
that the localized enrichment of Fn1 in the pharyngeal region may be essential
for cardiovascular morphogenesis. To test this hypothesis, we ablated Fn1 using
the Isl1(Cre) knock-in strain of mice. Deletion of Fn1 using the Isl1(Cre) strain
resulted in defective formation of the 4th pharyngeal arch arteries (PAAs),
aberrant development of the cardiac outflow tract (OFT), and ventricular septum
defects. To determine the cell types responding to Fn1 signaling during
cardiovascular development, we deleted a major Fn1 receptor, integrin alpha5
using the Isl1(Cre) strain, and observed the same spectrum of abnormalities seen
in the Fn1 conditional mutants. Additional conditional mutagenesis studies
designed to ablate integrin alpha5 in distinct cell types within the Isl1(+)
tissues and their derivatives, suggested that the expression of integrin alpha5
in the pharyngeal arch mesoderm, endothelium, surface ectoderm and the neural
crest were not required for PAA formation. Our studies suggest that an (as yet
unknown) integrin alpha5-dependent signal extrinsic to the pharyngeal endothelium
mediates the formation of the 4th PAAs.
PMID- 26434920
TI - Effect of two different healing times on the mineralization of newly formed bone
using a bovine bone substitute in sinus floor augmentation: a randomized,
controlled, clinical and histological investigation.
AB - PURPOSE: To investigate the amount of the mineralization of a bovine bone
substitute material in sinus floor augmentation after healing times of 3 and 6
months. MATERIALS AND METHODS: Fifty-one patients were randomized into two
healing time groups and received sinus floor augmentations with a bovine bone
material. After 3 or 6 months of healing, trephine bone biopsies were retrieved.
The biopsies were processed for histological and histomorphometric evaluations to
primarily investigate the amount of mineralized bone in the augmented area and
secondarily compare the amount of mineralized bone in the augmented area and in
the pristine bone. Statistical tests were performed to analyse the fraction of
the mineralized bone (p < 0.05). RESULTS: The biopsies of both groups showed
remnants of the well-integrated bone substitute material. The histology revealed
osteoblasts, osteocytes with osteoid, and osteoclasts. The mean percentage of
mineralized bone in the augmented area was 23.8% (3 months group) and 23.6% (6
months group; p = 0.9246); the amount of remaining bone substitute material was
35% (3 months group) and 33.9% (6 months group; p = 0.6325). CONCLUSION: It can
be concluded that the bone maturation in the augmented sinus using the bovine
bone material is similar after 3 and 6 months. Thus, implant installation after 3
months following a lateral window sinus floor augmentation approach using a
bovine bone material seems to be clinically acceptable.
PMID- 26434921
TI - Impact of case-relevant and case-irrelevant communication within the surgical
team on surgical-site infection.
AB - BACKGROUND: Surgical-site infections (SSIs) are the most common complications
after surgery. An influence from talking and distractions during surgery on
patient outcomes has been suggested, but there is limited evidence. The aim of
this prospective observational study was to assess the relationship between
intraoperative communication within the surgical team and SSI, and between
intraoperative distractions and SSI. METHODS: This prospective observational
study included patients undergoing elective, open abdominal procedures. For each
procedure, intraoperative case-relevant and case-irrelevant communication, and
intraoperative distractions were observed continuously on site. The influence of
communication and distractions on SSI after surgery was assessed using logistic
regressions, adjusting for risk factors. RESULTS: A total of 167 observed
procedures were analysed; their mean(s.d.) duration was 4.6(2.1) h. A total of 24
SSIs (14.4 per cent) were diagnosed. Case-relevant communication during the
procedure was independently associated with a reduced incidence of organ/space
SSI (propensity score-adjusted odds ratio 0.86, 95 per cent c.i. 0.77 to 0.97; P
= 0.014). Case-irrelevant communication during the closing phase of the procedure
was independently associated with increased incidence of incisional SSI
(propensity score-adjusted odds ratio 1.29, 1.08 to 1.55; P = 0.006).
Distractions had no association with SSI. CONCLUSION: More case-relevant
communication was associated with fewer organ/space SSIs, and more case
irrelevant communication during wound closure was associated with incisional SSI.
PMID- 26434922
TI - Pregnancy Outcomes in Women With Rare Autoimmune Diseases.
AB - OBJECTIVE: To examine pregnancy outcomes and pregnancy-related health service
utilization among women with rare autoimmune diseases. METHODS: This population
based cohort study of an Australian obstetric population (2001-2011) used birth
records linked to hospital records for identification of rare autoimmune diseases
including systemic vasculitis, vasculitis limited to the skin, Sjogren's
syndrome, systemic sclerosis, Behcet's disease, polymyositis/dermatomyositis, and
other systemic involvement of connective tissue. We excluded births in women with
systemic lupus erythematosus or rheumatoid arthritis as well as births occurring
>=6 months before the diagnosis of the rare autoimmune disease. Modified Poisson
regression was used to compare study outcomes between women with autoimmune
diseases and the general obstetric population. RESULTS: There were 991,701
births, including 409 births (0.04%) in 293 women with rare autoimmune diseases.
Of the 409 births, 202 (49%) were delivered by cesarean section and 72 (18%) were
preterm; these rates were significantly higher than those in the general
obstetric population (28% and 7%, respectively). Compared to the general
population, women with autoimmune diseases had higher rates of hypertensive
disorders, antepartum hemorrhage, and severe maternal morbidity and required
longer hospitalization at delivery, more hospital admissions, and tertiary
obstetric care. Compared to other infants, those whose mothers had a rare
autoimmune disease were at increased risk of admission to a neonatal intensive
care unit, severe neonatal morbidity, and perinatal death. CONCLUSION: While the
majority of women with rare autoimmune diseases delivered healthy infants, they
were at increased risk of having both maternal complications and adverse neonatal
outcomes, suggesting that their pregnancies should be closely monitored.
PMID- 26434923
TI - Non-target effects of commonly used plant protection products in roses on the
predatory mite Euseius gallicus Kreiter & Tixier (Acari: Phytoseidae).
AB - BACKGROUND: Euseius gallicus Kreiter & Tixier (Acari: Phytoseidae) is a predatory
mite recently available for use against various pests in roses. We tested in
greenhouse trials the impact on the numbers of eggs and motiles of E. gallicus of
the most commonly used plant protection products in roses in northern Europe: the
acaricides acequinocyl and etoxazole, the insecticides azadirachtin-A,
acetamiprid, flonicamid, imidacloprid, indoxacarb, thiacloprid and thiamethoxam
and the fungicides boscalid and kresoxim-methyl, cyprodinil + fludioxonil,
dodemorph and fluopyram + tebuconazole. RESULTS: The neonicotinoids thiacloprid,
thiamethoxam, acetamiprid and imidacloprid had a negative impact on the number of
eggs (47, 62, 81 and 76% reduction, respectively, compared with a water
treatment) and number of motiles of E. gallicus (42.2, 42.9, 59.9 and 60.6%
reduction) and were classified as slightly to moderately toxic. Also, the number
of motiles was reduced after treatment with acequinocyl (47%) and etoxazole
(43.9%) and after two treatments with flonicamid (41%) with a 1 week interval
between treatments. CONCLUSION: Azadirachtin-A, acetamiprid, flonicamid, boscalid
and kresoxim-methyl, cyprodinil + fludioxonil, dodemorph and fluopyram +
tebuconazole were harmless for E. gallicus. Special attention should be paid to
the impact of neonicotinoids and of acequinocyl and etoxazole, and to the
application frequency with flonicamid on E. gallicus. (c) 2015 Society of
Chemical Industry.
PMID- 26434924
TI - Changes in actin and tubulin expression in osteogenic cells cultured on bioactive
glass-based surfaces.
AB - The present study evaluated whether the changes in the labeling pattern of
cytoskeletal proteins in osteogenic cells cultured on bioactive glass-based
materials are due to altered mRNA and protein levels. Primary rat-derived
osteogenic cells were plated on Bioglass(r) 45S5, Biosilicate(r), and
borosilicate (bioinert control). The following parameters were assayed: (i)
qualitative epifluorescence analysis of actin and tubulin; (ii) quantitative mRNA
and protein expression for actin and tubulin by real-time PCR and ELISA,
respectively, and (iii) qualitative analysis of cell morphology by scanning
electron microscopy (SEM). At days 3 and 7, the cells grown on borosilicate
showed typical actin and tubulin labeling patterns, whereas those on the
bioactive materials showed roundish areas devoid of fluorescence signals. The
cultures grown on bioactive materials showed significant changes in actin and
tubulin mRNA expression that were not reflected in the corresponding protein
levels. A positive correlation between the mRNA and protein as well as an
association between epifluorescence imaging and quantitative data were only
detected for the borosilicate. SEM imaging of the cultures on the bioactive
surfaces revealed cells partly or totally coated with material aggregates, whose
characteristics resembled the substrate topography. The culturing of osteogenic
cells on Bioglass(r) 45S5 and Biosilicate(r) affect actin and tubulin mRNA
expression but not the corresponding protein levels. Changes in the labeling
pattern of these proteins should then be attributed, at least in part, to the
presence of a physical barrier on the cell surface as a result of the material
surface reactions, thus limiting fluorescence signals.
PMID- 26434925
TI - Theory of Mind in aging: Comparing cognitive and affective components in the faux
pas test.
AB - OBJECTIVES: Theory of Mind (ToM) is a complex human ability that allows people to
make inferences on others' mental states such as beliefs, emotions and desires.
Previous studies on ToM in normal aging have provided heterogeneous findings. In
the present study we examined whether a mixed calculation of different aspects of
ToM may have contributed to these conflicting results. We had two aims. First, we
explored the age-related changes in the performance of cognitive vs. affective
ToM. Second, we investigated the extent to which the effect of aging on cognitive
vs. affective ToM is mediated by age-related differences in executive functions.
METHOD: To address these issues three age groups (young, young-old, and old-old
adults) were compared on cognitive and affective ToM using the faux pas test. In
addition, participants were tested using a battery of executive function tasks
tapping on inhibition, working memory updating, and word fluency. RESULTS: The
analyses indicated that young adults outperform both young-old and old-old adults
on cognitive ToM but not on affective ToM. Correlations showed that, whereas
cognitive ToM was significantly associated with age, working memory updating, and
inhibition, affective ToM was not. Finally, analyses revealed that individual
differences in working memory updating (but not inhibition) mediated the effect
of age on cognitive ToM. CONCLUSION: Our findings support the view of selective
age-related differences on cognitive, but not affective, ToM in normal aging. The
distinction between the two ToM components is further supported by a dissociable
pattern of correlations with executive functions.
PMID- 26434926
TI - Non-specificity of ethylene inhibitors: 'double-edged' tools to find out new
targets involved in the root morphogenetic programme.
AB - In the last decade, genetic and pharmacological approaches have been used to
explore ethylene biosynthesis and perception in order to study the role of
ethylene and ethylene/auxin interaction in root architecture development.
However, recent findings with pharmacological approaches highlight the non
specificity of commonly used inhibitors. This suggests that caution is required
for interpreting these studies and that the use of pharmacological agents is a
'double-edged' tool. On one hand, non-specific effects make interpretation
difficult unless other experiments, such as with different mutants or with
multiple diversely acting chemicals, are conducted. On the other hand, the non
specificity of inhibitors opens up the possibility of uncovering some ligands or
modulators of new receptors such as plant glutamate-like receptors and importance
of some metabolic hubs in carbon and nitrogen metabolism such as the pyridoxal
phosphate biosynthesis involved in the regulation of the root morphogenetic
programme. Identification of such targets is a critical issue to improve the
efficiency of absorption of macronutrients in relation to root the morphogenetic
programme.
PMID- 26434927
TI - Bacillus subtilis vegetative isolate surviving chlorine dioxide exposure: an
elusive mechanism of resistance.
AB - AIMS: Oxidizing agents such as chlorine dioxide are widely used microbicides,
including for disinfection of medical equipment. We isolated a Bacillus subtilis
isolate from a washer-disinfector whose vegetative form demonstrated unique
resistance to chlorine dioxide (0.03%) and hydrogen peroxide (7.5%). The aim of
this study was to understand the mechanisms of resistance expressed by this
isolate. METHODS AND RESULTS: A range of resistance mechanisms were investigated
in the B. subtilis isolate and a reference B. subtilis strain (ATCC 6051) to
include bacterial cell aggregation, the presence of profuse exopolysaccharide
(EPS), and the expression of detoxification enzymes. The basis of resistance of
the isolate to high concentrations of oxidizing agents was not linked to the
presence of endospores. Although, the presence of EPS, aggregation and expression
of detoxification enzymes may play a role in bacterial survival to low
concentrations of chlorine dioxide, it is unlikely that the mechanisms helped
tested to survive the bactericidal effect of higher oxidizer concentrations.
CONCLUSIONS: Overall, the mechanisms conferring resistance to chlorine dioxide
and hydrogen peroxide remains elusive. Based on recent advances in the mode of
action of oxidizing agents and notably hydrogen peroxide, we postulate that
additional efficient intracellular mechanisms may be involved to explain
significant resistance to in-use concentrations of commonly used high-level
disinfectants. SIGNIFICANCE AND IMPACT OF STUDY: The isolation of a highly
resistant vegetative Gram-positive bacterium to a highly reactive oxidizing agent
is worrying. Understanding the mechanisms conferring such resistance is essential
to effectively control such bacterial isolates. Here, we postulate that there are
still mechanisms of bacterial resistance that have not been fully characterized.
PMID- 26434928
TI - Structure of the N-terminal domain of the metalloprotease PrtV from Vibrio
cholerae.
AB - The metalloprotease PrtV from Vibrio cholerae serves an important function for
the ability of bacteria to invade the mammalian host cell. The protein belongs to
the family of M6 proteases, with a characteristic zinc ion in the catalytic
active site. PrtV constitutes a 918 amino acids (102 kDa) multidomain pre-pro
protein that undergoes several N- and C-terminal modifications to form a
catalytically active protease. We report here the NMR structure of the PrtV N
terminal domain (residues 23-103) that contains two short alpha-helices in a
coiled coil motif. The helices are held together by a cluster of hydrophobic
residues. Approximately 30 residues at the C-terminal end, which were predicted
to form a third helical structure, are disordered. These residues are highly
conserved within the genus Vibrio, which suggests that they might be functionally
important.
PMID- 26434929
TI - Soft and Hard Tissue Changes around Tissue-Oriented Tulip-Design Implant
Abutments: A 1-Year Randomized Prospective Clinical Trial.
AB - BACKGROUND: The advantages of platform switching using narrower abutments remain
controversial. Many researchers suggest that platform switching can yield
enhanced clinical results, while others remain skeptical. We hypothesize that the
effectiveness of platform switching might be associated with the degree of
reduction in size of the abutment. PURPOSE: To radiographically and clinically
examine a new abutment design created to move the implant-abutment interface
farther medially. MATERIALS AND METHODS: This was a prospective, randomized
controlled clinical trial that included 27 patients (41 MIS Lance Plus(r)
implants; MIS Implant Technologies, Karmiel, Israel). The patients' age ranged
from 39 to 75 years. At the second stage of the surgery, the implants were
randomly assigned to either the new platform switch Tulip abutment (TA) design or
to the standard platform abutment (SA). Implant probing depth (IPD) and bleeding
on probing (BOP) were recorded at baseline and after 12 months. Standardized
periapical radiographs were taken (at baseline and at 12 months) and the marginal
bone height measured. RESULTS: All implants were successfully integrated. The
mean IPD at 1 year post-op was 2.91 mm for the SA group and 2.69 mm for the TA
group (p > .05). Similarly, the BOP at 1 year was almost identical in both
groups. The mean values of bone resorption at baseline were 0.98 +/- 0.37 mm and
0.69 +/- 0.20 for the TA and SA groups, respectively (p > .05). Bone loss
(baseline to 12 months) was significantly greater in the SA group compared with
the TA group. CONCLUSIONS: Use of the new TA, with its significantly downsized
diameter, resulted in reduced bone loss at 1 year. Further research will be
required to assess the long-term effect of this abutment on peri-implant health.
PMID- 26434930
TI - Colectomy with Permanent End Ileostomy Is More Cost-Effective than Ileal Pouch
Anal Anastomosis for Crohn's Colitis.
AB - BACKGROUND: Much of the economic burden of Crohn's disease (CD) is related to
surgery. Twenty percent of patients with CD have isolated colonic disease. While
permanent end ileostomy (EI) is generally the procedure of choice for patients
with refractory CD colitis, single-center experiences suggest that restorative
proctocolectomy (IPAA) is durable in select patients. AIMS: We assessed the cost
effectiveness of total colectomy with permanent EI versus IPAA in medically
refractory colonic CD. METHODS: We used a lifetime Markov model with 6-month
cycles to simulate quality-adjusted life years (QALYs) and cost. In each of the
EI and IPAA strategies, patients could transition between multiple health states.
One-way and multivariable sensitivity analysis and tornado analysis were
performed to identify thresholds for factors influencing cost-effectiveness.
RESULTS: IPAA was more effective than EI surgery with an incremental cost
effectiveness ratio of $70,715 per QALY gained. We identified the following
variables of importance in our model: (1) the cost of the EI surgery, (2) the
cost of infliximab, and (3) the cost of gastroenterology ambulatory visit and
labs. Threshold analysis revealed that if the costs associated with EI surgery
exceeded $20,167 or if the utility of IPAA with CD remission without medical
therapy exceeded 0.37, IPAA became the more cost-effective strategy. CONCLUSIONS:
In patients with medically refractory CD isolated to the colon, colectomy with
permanent EI is more cost-effective than IPAA unless the costs associated with
the EI surgery exceed $20,167 or if the utility associated with IPAA and CD
remission exceeds 0.37.
PMID- 26434931
TI - Significance of Endoscopic Sphincterotomy Preceding Endoscopic Papillary Large
Balloon Dilation in the Management of Bile Duct Stones.
AB - BACKGROUND: Endoscopic papillary large balloon dilation (EPLBD) is safe and
effective in management of common bile duct stones (CBDS). Endoscopic
sphincterotomy (EST) prior to EPLBD has been performed as a standard procedure.
However, the significance of EST prior to EPLBD has not been well studied yet.
AIMS: To compare the clinical outcomes of EPLBD with and without EST to evaluate
the significance of EST. METHODS: Between April 2010 and March 2015, a total of
82 patients with naive papillae underwent EPLBD with or without EST for the
management of CBDS. A retrospective analysis compared the efficacy and safety of
EPLBD with and without EST. RESULTS: Basic patient characteristics were not
significantly different between the groups that underwent EPLBD with EST (n = 27)
and without EST (n = 55). Complete stone removal rates were similar between the
groups (100 % in the EST group and 98 % in the non-EST group, p = 1.00). There
was no significant difference in the median balloon size (13 mm in both groups, p
= 0.445), rate of application of mechanical lithotripsy (26 vs. 35 % in the EST
and non-EST groups, respectively, p = 0.463), or the median procedure time (38
vs. 34 min in the EST and non-EST groups, respectively, p = 0.682). The overall
adverse event rates were not statistically different (4 vs. 7 % in the EST and
non-EST groups, respectively, p = 1.00). Pancreatitis, cholangitis, and
hemorrhage rates were also similar in both groups. CONCLUSIONS: EST prior to
EPLBD may be unnecessary since this study did not demonstrate its benefits.
PMID- 26434932
TI - GGPPS-mediated Rab27A geranylgeranylation regulates beta cell dysfunction during
type 2 diabetes development by affecting insulin granule docked pool formation.
AB - Loss of first-phase insulin secretion associated with beta cell dysfunction is an
independent predictor of type 2 diabetes mellitus (T2DM) onset. Here we found
that a critical enzyme involved in protein prenylation, geranylgeranyl
pyrophosphate synthase (GGPPS), is required to maintain first-phase insulin
secretion. GGPPS shows a biphasic expression pattern in islets of db/db mice
during the progression of T2DM: GGPPS is increased during the insulin
compensatory period, followed by a decrease during beta cell dysfunction. Ggpps
deletion in beta cells results in typical T2DM beta cell dysfunction, with
blunted glucose-stimulated insulin secretion and consequent insulin secretion
insufficiency. However, the number and size of islets and insulin biosynthesis
are unaltered. Transmission electron microscopy shows a reduced number of insulin
granules adjacent to the cellular membrane, suggesting a defect in docked granule
pool formation, while the reserve pool is unaffected. Ggpps ablation depletes
GGPP and impairs Rab27A geranylgeranylation, which is responsible for the docked
pool deficiency in Ggpps-null mice. Moreover, GGPPS re-expression or GGPP
administration restore glucose-stimulated insulin secretion in Ggpps-null islets.
These results suggest that GGPPS-controlled protein geranylgeranylation, which
regulates formation of the insulin granule docked pool, is critical for beta cell
function and insulin release during the development of T2DM.
PMID- 26434933
TI - Subtotal spleen necrosis.
PMID- 26434934
TI - AMG 151 (ARRY-403), a novel glucokinase activator, decreases fasting and
postprandial glycaemia in patients with type 2 diabetes.
AB - Phase I studies have shown that AMG 151 activates glucokinase, a key enzyme in
glucose homeostasis. The present randomized, placebo-controlled phase IIa study
evaluated the dose-effect relationship of the glucokinase activator AMG 151
relative to placebo on fasting plasma glucose (FPG) in 236 patients (33-35
patients per arm) with type 2 diabetes treated with metformin. Patients received
oral AMG 151 at 50, 100 or 200 mg twice daily, AMG 151 at 100, 200 or 400 mg once
daily or matching placebo for 28 days. A significant linear dose-effect trend was
observed with the twice-daily regimen (p = 0.004) for change in FPG to day 28. No
trend was observed with the once-daily regimen. A higher incidence of
hypoglycaemia and hypertriglyceridaemia was observed with AMG 151 administration.
AMG 151 significantly reduced FPG when administered twice daily but not when
administered once daily in patients with type 2 diabetes treated with metformin.
PMID- 26434935
TI - Systematic review with meta-analysis: the risk of major gastrointestinal bleeding
with non-vitamin K antagonist oral anticoagulants.
AB - BACKGROUND: Gastrointestinal (GI) bleeding is a common complication among
anticoagulated patients. Non-vitamin K antagonist oral anticoagulants (NOACs) are
associated with increased risk of GI (major and clinically relevant non-major)
bleeding. However, more information is needed regarding severe events. AIM: To
evaluate the risk of NOACs major GI bleeding. METHODS: We searched for phase III
randomised clinical trials (RCT) evaluating NOACs (apixaban, dabigatran, edoxaban
and rivaroxaban) and reporting major GI bleeding events, in MEDLINE, Cochrane
Library, SciELO collection and Web of Science databases (July 2015). Meta
analysis was performed to estimate risk ratio (RR) and 95% confidence intervals
(95% CIs). Heterogeneity was assessed with the I(2) test. RESULTS: A total of 23
studies were included. Among patients with atrial fibrillation, the risk of major
GI bleeding was not different between NOACs and vitamin K antagonists (VKA) (RR
1.08, 95% CI 0.85-1.36, I(2) = 78%; 5 RCTs) or acetylsalicylic acid (RR 0.78,
95% CI 0.36-1.72; 1 RCT). Similar results were found for patients undergoing
orthopaedic surgery and those with venous thromboembolism. NOACs were not found
to increase the risk compared to low-molecular-weight heparin (LWMH) alone (RR
1.42, 95% CI 0.55-3.71, I(2) = 7%; 8 RCTs), the sequential treatment with LMWH
VKA (RR 0.77, 95% CI 0.49-1.21, I(2) = 43%; 7 RCTs) or placebo (RR 1.48, 95% CI
0.15-14.84, I(2) = 21%; 2 RCTs). CONCLUSION: Despite previous evidence
supporting the association of non-vitamin K antagonist oral anticoagulants and
overall GI bleeding, non-vitamin K antagonist oral anticoagulants are not
associated with increased risk of major GI bleeding compared to other
anticoagulant drugs (with known increased risk of these events).
PMID- 26434936
TI - Conception rates in farm mink (Neovison vison) in relation to first mating date,
age and color variety.
AB - The aim of the study was to analyze the effects of the first mating date, age and
color variety on the conception rates in farm mink. We analyzed female mink
reproductive performance in 492 Sapphire and 463 Standard Black females over 3 or
4 years. The analysis included the number of inefficient matings, the interval
between the first inefficient mating and the efficient mating (copulation) and
the conception rates. The results show a significant effect of female's age and
color variety on the conception rates. The youngest, yearling females of either
color needed a higher number of matings per conception, as compared to older, 2-
and 3-year-old females. Black females demonstrated a higher number of inefficient
matings (1.066), as compared with Sapphires (0.730). Yearling females were most
often mated from 1 to 10 March, and older females from 11 to 20 March. Older
females achieved better conception rates than the yearlings. Dates between 11 and
25 March proved to be the optimum for the first mating, since the highest
conception rates were observed if the females had mated during this period.
PMID- 26434938
TI - Use of hormonal contraception after hydatidiform mole.
PMID- 26434937
TI - Ultrastructural changes of mitochondria in human retinoblastoma: correlation with
tumor differentiation and invasiveness.
AB - Retinoblastoma still represents a challenge for pediatric tumors. Mitochondria
have been implicated in tumor progression, cell differentiation, and apoptotic
pathways. Electron microscopy allows the study of mitochondrial morphology and it
is still debated in human retinoblastoma. Demographic, clinical, and
histopathological parameters were recorded in 17 enucleated retinoblastoma
specimens. Hematoxylin and eosin staining was performed to study tumor
characteristics and the extent of invasion in ocular structures. The aim of this
study was to describe and analyze the mitochondrial morphology in human
retinoblastoma by transmission electron microscopy (TEM). There was a male
preponderance in our study. Ages ranged from 2 to 78 months. Histopathological
analysis revealed that 15 (88.2 %) tumors were poorly differentiated
retinoblastomas. Massive choroidal invasion was the most frequent
histopathological high-risk factor among the others. Histopathological high-risk
factors were found in 7/17 (41.1 %) cases. Tumor samples of all patients were
examined by means of TEM. All cases showed tumor cells with high
nucleocytoplasmic ratio. Poorly differentiated retinoblastoma cases showed fewer
mitochondria, scant cytoplasm, disorganized organelles (mitochondria), and
necrosis, whereas well-differentiated retinoblastomas had larger number of
mitochondria and more organized organelles. However, there was no significant
difference in mitochondrial changes between invasive and noninvasive tumors. Our
study observed that cristolysis and swollen mitochondria were more frequent in
retinoblastoma tumors. Understanding the structural and functional
characteristics of mitochondria in retinoblastoma might be essential for the
design of future therapeutic strategies. The authors have no proprietary or
commercial interest in any materials discussed in this article.
PMID- 26434939
TI - Simultaneous determination of aminopyrine and antipyrine in porcine muscle, milk,
and eggs using liquid chromatography with tandem mass spectrometry.
AB - The concentrations of residual aminopyrine and antipyrine in porcine muscle,
milk, and egg samples were analyzed using liquid chromatography with tandem mass
spectrometry after undergoing a series of sample pretreatment steps. Owing to an
ion suppression effect, matrix-matched calibrations were used for analyte
quantitation with determination coefficients (R(2) ) >= 0.9931. The recovery
rates for aminopyrine and antipyrine in various matrices at two spiking levels (5
and 10 ng/g) fell in the range of 60.96-68.87 and 61.87-66.99%, respectively.
Meanwhile, the intra- and inter-day precisions (expressed as relative standard
deviation) were 1.02-12.95 and 1.71-5.50%, respectively. The method's detection
limit (1 ng/g) was very low, thus enabling the detection of low residue levels.
The applicability of the developed method was demonstrated with actual market
samples and none of the tested analytes was detected in any of the samples.
PMID- 26434940
TI - Spatio-temporal dynamics of mosquitoes in stream pools of a biosphere reserve of
Southern Western Ghats, India.
AB - The spatial and temporal dynamics of mosquitoes in stream pools were examined in
a biosphere reserve of the Southern Western Ghats, India. The immature mosquitoes
in stream pools were collected from stream substrates of bedrock pool, boulder
cavity and sand puddle. The collected larvae and pupae were reared and
identified. In total, 16 species from four genera of mosquitoes were collected.
The mosquito species from Culex and Anopheles were predominantly occurred. The
bedrock pool had the highest diversity and abundance of mosquitoes. The
statistical analyses showed that the substrate specificity and the seasons were
positively related to the distribution of mosquitoes rather than spatial pattern.
This study described the spatial and temporal pattern of mosquitoes in stream
pools of the Southern Western Ghats. This information would be helpful to
National Vector borne disease control program for surveillance and control.
PMID- 26434941
TI - Combinatorial therapy for triple negative breast cancer using hyperstar polymer
based nanoparticles.
AB - We report the ability of a novel combinatorial therapy obtained from
nanoparticles of hyperstar polymers encompassing drugs to selectively target
triple negative breast cancer (TNBC) cell proliferation through STAT3 and
topoisomerase-II pathways. This nano-cocktail was at least two to four fold
better than the individual drugs and 6-20 times more selective than the parent
drugs.
PMID- 26434942
TI - Selective functionalization of mesoporous silica nanoparticles with ibuprofen and
Gd(III) chelates: a new probe for potential theranostic applications.
AB - Organo-modified mesoporous silica nanoparticles, loaded with ibuprofen into the
pores and functionalized on the external surface with a stable Gd(iii)-DOTA
monoamide chelate, were prepared and explored as potential theranostic probes.
PMID- 26434943
TI - From Dibismuthenes to Three- and Two-Coordinated Bismuthinidenes by Fine Ligand
Tuning: Evidence for Aromatic BiC3N Rings through a Combined Experimental and
Theoretical Study.
AB - The reduction of N,C,N-chelated bismuth chlorides [C6H3-2,6-(CH=NR)2]BiCl2 [where
R = tBu (1), 2',6'-Me2C6H3 (2), or 4'-Me2NC6H4 (3)] or N,C-chelated analogues
[C6H2-2-(CH=N-2',6'-iPr2C6H3)-4,6-(tBu)2]BiCl2 (4) and [C6H2-2-(CH2NEt2)-4,6
(tBu)2]BiCl2 (5) is reported. Reduction of compounds 1-3 gave monomeric N,C,N
chelated bismuthinidenes [C6H3-2,6-(CH=NR)2]Bi [where R = tBu (6), 2',6'-Me2C6H3
(7) or 4'-Me2NC6H4 (8)]. Similarly, the reduction of 4 led to the isolation of
the compound [C6H2-2-(CH=N-2',6'-iPr2C6H3)-4,6-(tBu)2]Bi (9) as an unprecedented
two-coordinated bismuthinidene that has been structurally characterized. In
contrast, the dibismuthene {[C6H2-2-(CH2NEt2)-4,6-(tBu)2]Bi}2 (10) was obtained
by the reduction of 5. Compounds 6-10 were characterized by using (1)H and (13)C
NMR spectroscopy and their structures, except for 7, were determined with the
help of single-crystal X-ray diffraction analysis. It is clear that the structure
of the reduced products (bismuthinidene versus dibismuthene) is ligand-dependent
and particularly influenced by the strength of the N->Bi intramolecular
interaction(s). Therefore, a theoretical survey describing the bonding situation
in the studied compounds and related bismuth(I) systems is included. Importantly,
we found that the C3NBi chelating ring in the two-coordinated bismuthinidene 9
exhibits significant aromatic character by delocalization of the bismuth lone
pair.
PMID- 26434948
TI - CRISPR/Cas9 system as an innovative genetic engineering tool: Enhancements in
sequence specificity and delivery methods.
AB - While human gene therapy has gained significant attention for its therapeutic
promise, CRISPR/Cas9 technology has made a breakthrough as an efficient genome
editing tool by emulating prokaryotic immune defense mechanisms. Although many
studies have found that CRISPR/Cas9 technology is more efficient, specific and
manipulable than previous generations of gene editing tools, it can be further
improved by elevating its overall efficiency in a higher frequency of genome
modifications and reducing its off-target effects. Here, we review the
development of CRISPR/Cas9 technology, focusing on enhancement of its sequence
specificity, reduction of off-target effects and delivery systems. Moreover, we
describe recent successful applications of CRISPR/Cas9 technology in laboratory
and clinical studies.
PMID- 26434949
TI - Multisource Synergistic Electrocatalytic Oxidation Effect of Strongly Coupled PdM
(M = Sn, Pb)/N-doped Graphene Nanocomposite on Small Organic Molecules.
AB - A series of palladium-based catalysts of metal alloying (Sn, Pb) and/or (N-doped)
graphene support with regular enhanced electrocatalytic activity were
investigated. The peak current density (118.05 mA cm(-2)) of PdSn/NG is higher
than the sum current density (45.63 + 47.59 mA cm(-2)) of Pd/NG and PdSn/G. It
reveals a synergistic electrocatalytic oxidation effect in PdSn/N-doped graphene
Nanocomposite. Extend experiments show this multisource synergetic catalytic
effect of metal alloying and N-doped graphene support in one catalyst on small
organic molecule (methanol, ethanol and Ethylene glycol) oxidation is universal
in PdM(M = Sn, Pb)/NG catalysts. Further, The high dispersion of small
nanoparticles, the altered electron structure and Pd(0)/Pd(II) ratio of Pd in
catalysts induced by strong coupled the metal alloying and N-doped graphene are
responsible for the multisource synergistic catalytic effect in PdM(M = Sn, Pb)
/NG catalysts. Finally, the catalytic durability and stability are also greatly
improved.
PMID- 26434947
TI - Development of next-generation respiratory virus vaccines through targeted
modifications to viral immunomodulatory genes.
AB - Vaccines represent one of the greatest contributions of the scientific community
to global health. Yet, many pathogens remain either unchallenged or inadequately
hindered by commercially available vaccines. Respiratory viruses pose distinct
and difficult challenges due to their ability to rapidly spread, adapt, and
modify the host immune response. Considerable research has been directed to
understand the role of respiratory virus immunomodulatory proteins and how they
influence the host immune response. We review here efforts to develop next
generation vaccines through targeting these key immunomodulatory genes in
influenza virus, coronaviruses, respiratory syncytial virus, measles virus, and
mumps virus.
PMID- 26434950
TI - Anthropogenic effects on a tropical forest according to the distance from human
settlements.
AB - The protection of tropical forests is one of the most urgent issues in
conservation biology because of the rapid deforestation that has occurred over
the last 50 years. Even in protected forests, the anthropogenic effects from
newly expanding villages such as harvesting of medicinal plants, pasturing cattle
and forest fires can induce environmental modifications, especially on the forest
floor. We evaluated the anthropogenic effects of the daily activities of
neighboring residents on natural forests in 12 plots extending from the village
boundary into a natural forest in Thailand. The basal area per unit land area did
not present a significant trend; however, the species diversity of woody plants
decreased linearly towards the village boundary, which caused a loss of
individual density because of severe declines in small saplings compared with
adult trees and large saplings in proximity to the village. An analysis of tree
size categories indicates a lack of small samplings near the village boundary.
The current forest appears to be well protected based on the adult tree canopy,
but regeneration of the present-day forests is unlikely because of the loss of
seedlings.
PMID- 26434952
TI - Hepatitis E virus: seroprevalence and frequency of viral RNA detection among US
blood donors.
AB - BACKGROUND: Hepatitis E virus (HEV) is a nonenveloped emerging virus of
increasing worldwide interest. Antibody prevalence, RNA frequencies, and
transfusion transmissions have been reported. We investigated the HEV RNA and
antibody frequencies in US blood donors. STUDY DESIGN AND METHODS: Individual
donation HEV RNA testing was performed on 18,829 donations from six US geographic
regions using a CE-marked nucleic acid test (95% limit of detection, 7.9 IU/mL).
Repeat-reactive donations were confirmed by in-house, real-time polymerase chain
reaction (PCR; 10.3 IU/mL). Total HEV seroprevalence in a randomly selected
subset of donations (n = 4499) was assessed by a direct, double-antigen sandwich
assay; reactives were further tested for immunoglobulin (Ig)G and IgM. As part of
the total antibody confirmatory algorithm, the cutoff was adjusted. RESULTS: Two
donations tested confirmed-positive for RNA (PCR not quantifiable, IgM/IgG
positive; and 14 IU/mL, antibody negative) for a frequency of 1 in 9500 (95%
confidence interval [CI], 1:2850-1:56,180) and 99.96% specificity (95% CI, 99.92%
99.98%); both donors were from the Midwest United States. Antibody prevalence was
9.5% (95% CI, 8.7-10.5) before the cutoff adjustment and 7.7% (95% CI, 7.0%-8.5%)
after adjustment; 0.58% (95% CI, 0.39%-0.85%) were IgM positive. CONCLUSIONS: We
confirmed comparatively low rates and low viral loads of HEV RNA in US blood
donors indicating the need for individual-donation testing if screening is
implemented. Antibody prevalence rates were comparable to those reported by one
US study using a different assay, but lower than those reported in another study
using yet a third assay. We did not answer the question of whether US blood
donation screening is warranted. Selective strategies involving providing HEV
negative blood to severely immunosuppressed patients at risk of developing
hepatitis may be considered.
PMID- 26434951
TI - An ace-1 gene duplication resorbs the fitness cost associated with resistance in
Anopheles gambiae, the main malaria mosquito.
AB - Widespread resistance to pyrethroids threatens malaria control in Africa.
Consequently, several countries switched to carbamates and organophophates
insecticides for indoor residual spraying. However, a mutation in the ace-1 gene
conferring resistance to these compounds (ace-1(R) allele), is already present.
Furthermore, a duplicated allele (ace-1(D)) recently appeared; characterizing its
selective advantage is mandatory to evaluate the threat. Our data revealed that a
unique duplication event, pairing a susceptible and a resistant copy of the ace-1
gene spread through West Africa. Further investigations revealed that, while ace
1(D) confers less resistance than ace-1(R), the high fitness cost associated with
ace-1(R) is almost completely suppressed by the duplication for all traits
studied. ace-1 duplication thus represents a permanent heterozygote phenotype,
selected, and thus spreading, due to the mosaic nature of mosquito control. It
provides malaria mosquito with a new evolutionary path that could hamper
resistance management.
PMID- 26434954
TI - Strong magnetic frustration and anti-site disorder causing spin-glass behavior in
honeycomb Li2RhO3.
AB - With large spin-orbit coupling, the electron configuration in d-metal oxides is
prone to highly anisotropic exchange interactions and exotic magnetic properties.
In 5d(5) iridates, given the existing variety of crystal structures, the magnetic
anisotropy can be tuned from antisymmetric to symmetric Kitaev-type, with
interaction strengths that outsize the isotropic terms. By many-body electronic
structure calculations we here address the nature of the magnetic exchange and
the intriguing spin-glass behavior of Li2RhO3, a 4d(5) honeycomb oxide. For
pristine crystals without Rh-Li site inversion, we predict a dimerized ground
state as in the isostructural 5d(5) iridate Li2IrO3, with triplet spin dimers
effectively placed on a frustrated triangular lattice. With Rh-Li anti-site
disorder, we explain the observed spin-glass phase as a superposition of
different, nearly degenerate symmetry-broken configurations.
PMID- 26434953
TI - p38 MAPK regulates PKAalpha and CUB-serine protease in Amphibalanus amphitrite
cyprids.
AB - The MKK3-p38 MAPK pathway has been reported to mediate larval settlement in
Amphibalanus (=Balanus) amphitrite. To clarify the underlying molecular
mechanism, we applied label-free proteomics to analyze changes in the proteome of
cyprids treated with a p38 MAPK inhibitor. The results showed that the expression
levels of 80 proteins were significantly modified (p < 0.05). These
differentially expressed proteins were assigned to 15 functional groups according
to the KOG database and 9 pathways were significantly enriched. Further analysis
revealed that p38 MAPK might regulate the energy supply and metamorphosis. Two
potential regulatory proteins, CUB-serine protease and PKAalpha, were both down
regulated in expression. CUB-serine protease localized to postaxial seta 2 and 3,
as well as the 4 subterminal sensilla in the antennule. Importantly, it was co
localized with the neuron transmitter serotonin in the sections, suggesting that
the CUB-serine protease was present in the neural system. PKAalpha was highly
expressed during the cyprid and juvenile stages, and it was co-localized with
phospho-p38 MAPK (pp38 MAPK) to the cement gland, suggesting that PKAalpha might
have some functions in cement glands. Overall, p38 MAPK might regulate multiple
functions in A. amphitrite cyprids, including the energy supply, metamorphosis,
neural system and cement glands.
PMID- 26434955
TI - Theoretical Elucidation of Glucose Dehydration to 5-Hydroxymethylfurfural
Catalyzed by a SO3H-Functionalized Ionic Liquid.
AB - While the catalytic conversion of glucose to 5-hydroxymethyl furfural (HMF)
catalyzed by SO3H-functioned ionic liquids (ILs) has been achieved successfully,
the relevant molecular mechanism is still not understood well. Choosing 1-butyl-3
methylimidazolium chloride [C4SO3HmimCl] as a representative of SO3H-functioned
IL, this work presents a density functional theory (DFT) study on the catalytic
mechanism for conversion of glucose into HMF. It is found that the conversion may
proceed via two potential pathways and that throughout most of elementary steps,
the cation of the IL plays a substantial role, functioning as a proton shuttle to
promote the reaction. The chloride anion interacts with the substrate and the
acidic proton in the imidazolium ring via H-bonding, as well as provides a polar
environment together with the imidazolium cation to stabilize intermediates and
transition states. The calculated overall barriers of the catalytic conversion
along two potential pathways are 32.9 and 31.0 kcal/mol, respectively, which are
compatible with the observed catalytic performance of the IL under mild
conditions (100 degrees C). The present results provide help for rationalizing
the effective conversion of glucose to HMF catalyzed by SO3H-functionalized ILs
and for designing IL catalysts used in biomass conversion chemistry.
PMID- 26434956
TI - Opportunities, Risks, and Limitations of Genetic Testing: Looking to the Future
From Patients' Point of View.
PMID- 26434957
TI - Impact of Statins on Physical Activity and Fitness: Ally or Adversary?
PMID- 26434958
TI - Hyponatremia Management: Walking the Tightrope Without a Net.
PMID- 26434959
TI - Living at Risk: Factors That Affect the Experience of Direct-to-Consumer Genetic
Testing.
PMID- 26434960
TI - Whole-Exome Sequencing of 10 Scientists: Evaluation of the Process and Outcomes.
AB - OBJECTIVE: To understand motivations, educational needs, and concerns of
individuals contemplating whole-exome sequencing (WES) and determine what amount
of genetic information might be obtained by sequencing a generally healthy cohort
so as to more effectively counsel future patients. PATIENTS AND METHODS: From
2012 to 2014, 40 medically educated, generally healthy scientists at Mayo Clinic
were invited to have WES conducted on a research basis; 26 agreed to be in a
drawing from which 10 participants were selected. The study involved pre- and
posttest genetic counseling and completion of 4 surveys related to the experience
and outcomes. Whole-exome sequencing was conducted on DNA from blood from each
person. RESULTS: Most variants (76,305 per person; range, 74,505-77,387) were
known benign allelic variants, variants in genes of unknown function, or variants
of uncertain significance in genes of known function. The results of suspected
pathogenic/pathogenic variants in Mendelian disorders and pharmacogenomic
variants were disclosed. The mean number of suspected pathogenic/pathogenic
variants was 2.2 per person (range, 1-4). Four pharmacogenomic genes were
included for reporting; variants were found in 9 of 10 participants. CONCLUSION:
This study provides data that may be useful in establishing reality-based patient
expectations, outlines specific points to cover during counseling, and increases
confidence in the feasibility of providing adequate preparation and counseling
for WES in generally healthy individuals.
PMID- 26434961
TI - Effects of Statin Therapy on Exercise Levels in Participants in the National
Runners' and Walkers' Health Study.
AB - OBJECTIVES: To determine whether decreases in exercise 1) were greater in
individuals who were diagnosed as having hypercholesterolemia than in those
without the diagnosis during follow-up and 2) were greater in incident
hypercholesterolemic participants starting statins than in those not treated with
cholesterol-lowering medications. PARTICIPANTS AND METHODS: Regression analyses
of changes since baseline (Delta) in exercise vs diagnosis of
hypercholesterolemia and its treatment in 66,377 runners and 12,031 walkers not
using cholesterol medications at baseline who were resurveyed during the National
Runners' and Walkers' Health Study follow-up (January 1, 1991, through December
31, 2006). RESULTS: A total of 3510 runners began statin treatment, 1779 began
other or unspecified cholesterol-lowering drug treatment, and 2583 had untreated
hypercholesterolemia; 58,505 runners remained nonhypercholesterolemic controls
during the mean 7.2-year follow-up. Usual distance run decreased significantly
more in hypercholesterolemic runners who began taking statins (mean +/- SE:
0.47+/-0.06 km/d) than in runners who remained nonhypercholesterolemic during
follow-up (-0.08+/-0.02 km/d) (P<.001). However, running distance also decreased
significantly more in hypercholesterolemic runners who began unspecified/other (
0.52+/-0.08 km/d) or no (-0.47+/-0.07 km/d) cholesterol drugs than in
nonhypercholesterolemic runners during follow-up. Moreover, Deltarunning distance
did not differ significantly between hypercholesterolemic runners who were statin
treated vs those treated with other/unspecified (P=.64) or no (P=.94) cholesterol
drugs. Initiating statin therapy was not associated with Deltarunning pace in
hypercholesterolemic runners or Deltawalking distances in hypercholesterolemic
walkers. CONCLUSION: These results are consistent with the premise that a
decrease in running distance is associated with hypercholesterolemia and do not
suggest that statins reduce exercise level or intensity.
PMID- 26434962
TI - Sodium Correction Practice and Clinical Outcomes in Profound Hyponatremia.
AB - OBJECTIVES: To assess the epidemiology of nonoptimal hyponatremia correction and
to identify associated morbidity and in-hospital mortality. PATIENTS AND METHODS:
An electronic medical record search identified all patients admitted with
profound hyponatremia (sodium <120 mmol/L) from January 1, 2008, through December
31, 2012. Patients were classified as having optimally or nonoptimally corrected
hyponatremia at 24 hours after admission. Optimal correction was defined as
sodium correction in 24 hours of 6 through 10 mmol/L. We investigated the
association between sodium correction and demographic and outcome variables,
including occurrence of osmotic demyelination syndrome (ODS). Baseline
characteristics by correction outcome categories were compared using the Kruskal
Wallis test for continuous variables and the chi(2) test for categorical
variables. Odds ratios for in-hospital mortality between groups were assessed
using logistic regression. Adjusted differences in hospital length of stay (LOS)
and intensive care unit (ICU) LOS were assessed using the Dunnett 2-tailed t
test. RESULTS: A total of 412 patients satisfied inclusion criteria of whom 174
(42.2%) were admitted to the ICU. A total of 211 (51.2%) had optimal correction
of their hyponatremia at 24 hours, 87 (21.1%) had undercorrected hyponatremia,
and 114 (27.9%) had overcorrected hyponatremia. Both patient factors and
treatment factors were associated with nonoptimal correction. There was a single
case of ODS. Overcorrection was not associated with in-hospital mortality or ICU
LOS. When adjusted for patient factors, undercorrection of profound hyponatremia
was associated with an increase in hospital LOS (9.3 days; 95% CI, 1.9-16.7
days). CONCLUSION: Nonoptimal correction of profound hyponatremia is common.
Fortunately, nonoptimal correction is associated with serious morbidity only
infrequently.
PMID- 26434964
TI - Answers to Common Questions About the Use and Safety of CT Scans.
AB - Articles in the scientific literature and lay press over the past several years
have implied that computed tomography (CT) may cause cancer and that physicians
and patients must exercise caution in its use. Although there is broad agreement
on the latter point--unnecessary medical tests of any type should always be
avoided--there is considerable controversy surrounding the question of whether,
or to what extent, CT scans can lead to future cancers. Although the doses used
in CT are higher than those used in conventional radiographic examinations, they
are still 10 to 100 times lower than the dose levels that have been reported to
increase the risk of cancer. Despite the fact that at the low doses associated
with a CT scan the risk either is too low to be convincingly demonstrated or does
not exist, the magnitude of the concern among patients and some medical
professionals that CT scans increase cancer risk remains unreasonably high. In
this article, common questions about CT scanning and radiation are answered to
provide physicians with accurate information on which to base their medical
decisions and respond to patient questions.
PMID- 26434963
TI - Association of Cardiorespiratory Fitness With Coronary Heart Disease in
Asymptomatic Men.
AB - OBJECTIVE: To examine the association of cardiorespiratory fitness (CRF) with
risk of coronary heart disease (CHD) while controlling for an individual's
Framingham Risk Score (FRS)-predicted CHD risk. PATIENTS AND METHODS: The study
included 29,854 men from the Aerobics Center Longitudinal Study, who received a
baseline examination from January 1, 1979, to December 31, 2002. Coronary heart
disease events included self-reported myocardial infarction or revascularization
or CHD death. Multivariable survival analysis investigated the association
between CRF, FRS, and CHD. Cardiorespiratory fitness was analyzed as both a
continuous and a categorical variable. The population was stratified by "low" and
"moderate or high" risk of CHD to test for differences in the FRS stratified by
CRF. RESULTS: Compared with men without incident CHD, men with incident CHD were
older (mean age, 51.6 years vs 44.6 years), had lower average maximally achieved
fitness (10.9 metabolic equivalent of tasks vs 12.0 metabolic equivalent of tasks
[METs]), and were more likely to have moderate or high 10-year CHD risk (P<.001).
Cardiorespiratory fitness, defined as maximal METs, exhibited a 20% lower risk of
CHD (hazard ratio, 0.80; 95% CI, 0.77-0.83) for each 1-unit MET increase. Among
men in the low CRF strata, individuals with moderate or high 10-year CHD risk,
according to the FRS, had a higher CHD risk (hazard ratio, 6.55; 95% CI, 3.64
11.82) than men with low CHD risk according to the FRS. CONCLUSION: Clinicians
should promote physical activity to improve CRF so as to reduce CHD risk, even to
patients with otherwise low CHD risk.
PMID- 26434965
TI - The Role of Environmental Exposures in the Etiology of Eosinophilic Esophagitis:
A Systematic Review.
AB - Eosinophilic esophagitis (EoE) is an emerging clinicopathologic entity defined by
abnormal esophageal eosinophilic infiltration. Management of this disease is
hampered by limited understanding of etiologic and controllable risk factors. The
aim of this systematic review was to determine the environmental risk factors for
EoE. We searched the PubMed, Web of Science, and EMBASE databases from January 1,
1950, through June 30, 2015. To identify additional relevant studies, we hand
searched bibliographies of included articles. We limited the review to articles
using human subjects and consisting of case reports, case series, cross-sectional
and cohort studies, and clinical trials. Nineteen articles discuss the risk of
environmental exposures on EoE and indicate that environment plays a large role
in the etiology of EoE. Seasonal, geographic, and climate-based differences in
disease prevalence have been reported, but the exact mediators of this process,
possibly aeroallergens that vary over time and from place to place, remain
elusive.
PMID- 26434966
TI - Food Allergy: Common Causes, Diagnosis, and Treatment.
AB - Food allergy is a growing concern, and recognition of symptoms, knowledge of
common food allergens, and management of reactions are important for patients and
practitioners. Symptoms of a classic IgE-mediated food allergy vary in severity
and can include any combination of laryngeal edema, wheezing, nausea, vomiting,
diarrhea, urticaria, angioedema, and hypotension. Many foods can induce an
allergic reaction, but the most commonly implicated foods include cow's milk,
egg, peanut, tree nut, soy, wheat, fish, and shellfish. Milk and egg allergy
generally develop and are outgrown in childhood. Peanut and tree nut allergy can
occur during childhood or adulthood, are less likely to be outgrown, and tend to
cause more fatal reactions. Given the possibility of life-threatening reactions,
it is important to recognize the potential for cross-reactivity among food
groups. Diagnosis of food allergy includes skin prick testing, specific serum IgE
testing, and oral food challenges. Management is centered on avoidance of
allergenic and cross-reacting foods and early recognition and immediate treatment
of reactions. Treatment protocols to desensitize patients to food are currently
under investigation.
PMID- 26434967
TI - 50-Year-Old Man With New-Onset Acute Kidney Injury.
PMID- 26434968
TI - Cancer Pain Management.
AB - Safe, effective, and evidence-based management of cancer-related pain is a
cornerstone of comprehensive cancer care. Despite increasing interest in and
efforts to improve its management, pain remains poorly controlled in nearly half
of all patients with cancer, with little change in the past 20 years. Limited
training in pain assessment and management, overestimation of providers' own
skills to treat pain, and failure to refer patients to pain specialists can
result in suboptimal pain management with devastating effects on quality of life,
physical functioning, and increased psychological distress. From a thorough
assessment of cancer-related pain to appropriate treatments that may include
opiates, adjuvant medications, nerve blocks, and nondrug interventions, this
article is intended as a brief overview of the mechanisms and types of pain as
well as a review of current, new, and promising approaches to its management.
PMID- 26434970
TI - Teachable Action for Leaders Committed to Improving Physician Work Life:
Continuing Education.
PMID- 26434971
TI - Vinpocetine: An Unapproved Drug Sold as a Dietary Supplement.
PMID- 26434969
TI - Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015.
AB - Few neoplastic diseases have undergone a transformation in a relatively short
period like chronic myeloid leukemia (CML) has in the last few years. In 1960,
CML was the first cancer in which a unique chromosomal abnormality was identified
and a pathophysiologic correlation suggested. Landmark work followed, recognizing
the underlying translocation between chromosomes 9 and 22 that gave rise to this
abnormality and, shortly afterward, the specific genes involved and the
pathophysiologic implications of this novel rearrangement. Fast forward a few
years and this knowledge has given us the most remarkable example of a specific
therapy that targets the dysregulated kinase activity represented by this
molecular change. The broad use of tyrosine kinase inhibitors has resulted in an
improvement in the overall survival to the point where the life expectancy of
patients today is nearly equal to that of the general population. Still, there
are challenges and unanswered questions that define the reasons why the progress
still escapes many patients, and the details that separate patients from ultimate
cure. In this article, we review our current understanding of CML in 2015,
present recommendations for optimal management, and discuss the unanswered
questions and what could be done to answer them in the near future.
PMID- 26434972
TI - Nonictal Near Sudden Unexpected Death in Epilepsy.
PMID- 26434973
TI - Iron-Deficiency Anemia With an Itch.
PMID- 26434974
TI - 63-Year-Old Woman With Generalized Fatigue and Left Flank Pain.
PMID- 26434975
TI - Ernesto "Che" Guevara de la Serna: Argentinian Marxist Revolutionary.
PMID- 26434978
TI - Porphyrin Metalation at the MgO Nanocube/Toluene Interface.
AB - Molecular insights into porphyrin adsorption on nanostructured metal oxide
surfaces and associated ion exchange reactions are key to the development of
functional hybrids for energy conversion, sensing, and light emission devices.
Here we investigated the adsorption of tetraphenyl-porphyrin (2HTPP) from toluene
solution on two types of MgO powder. We compare MgO nanocubes with an average
size d < 10 nm and MgO cubes with 10 nm <= d <= 1000 nm. Using molecular
spectroscopy techniques such as UV/vis transmission and diffuse reflectance (DR),
photoluminescence (PL), and diffuse reflectance infrared Fourier-transform
(DRIFT) spectroscopy in combination with structural characterization techniques
(powder X-ray diffraction and transmission electron microscopy, TEM), we
identified a new room temperature metalation reaction that converts 2HTPP into
magnesium tetraphenyl-porphyrin (MgTPP). Mg(2+) uptake from the MgO nanocube
surfaces and the concomitant protonation of the oxide surface level off at a
concentration that corresponds to roughly one monolayer equivalent adsorbed on
the MgO nanocubes. Larger MgO cubes, in contrast, show suppressed exchange, and
only traces of MgTPP can be detected by photoluminescence.
PMID- 26434979
TI - Investigation and Sensory Characterization of 1,4-Cineole: A Potential Aromatic
Marker of Australian Cabernet Sauvignon Wine.
AB - This work reports the quantitation and sensory characterization of 1,4-cineole in
red wine for the first time. A headspace-solid-phase microextraction-gas
chromatography-mass spectrometry (HS-SPME-GC-MS) method was developed to
quantitate 1,4-cineole and 1,8-cineole in 104 commercial Australian red wines.
1,4-Cineole was detected in all of the wines analyzed, with concentrations
ranging from 0.023 to 1.6 MUg/L. An important varietal effect was observed, with
concentrations of 1,4-cineole in Cabernet Sauvignon wines (mean of 0.6 +/- 0.3
MUg/L) significantly higher than in Shiraz (0.07 +/- 0.04 MUg/L) and Pinot Noir
(0.2 +/- 0.2 MUg/L) wines. Regional variations of both cineole isomer
concentrations have been measured between wines originating from different
Australian regions. Sensory studies demonstrated that the addition of 0.54 MUg/L
1,4-cineole in a Cabernet Sauvignon wine, to produce a final concentration of
0.63 MUg/L, was perceived significantly by a sensory panel (p < 0.05).
Descriptive analyses revealed that 1,4-cineole and 1,8-cineole may contribute to
the hay, dried herbs, and blackcurrant aromas reported in Australian Cabernet
Sauvignon wines and may be potential markers of regional typicality of these
wines.
PMID- 26434980
TI - Colorimetric Signal Amplification Assay for Mercury Ions Based on the Catalysis
of Gold Amalgam.
AB - Mercury is a major threat to the environment and to human health. It is highly
desirable to develop a user-friendly kit for on-site mercury detection. Such a
method must be able to detect mercury below the threshold levels (10 nM) for
drinking water defined by the U.S. Environmental Protection Agency. Herein, we
for the first time reported catalytically active gold amalgam-based reaction
between 4-nitrophenol and NaBH4 with colorimetric sensing function. We take
advantage of the correlation between the catalytic properties and the surface
area of gold amalgam, which is proportional to the amount of the gold
nanoparticle (AuNP)-bound Hg(2+). As the concentration of Hg(2+) increases until
the saturation of Hg onto the AuNPs, the catalytic performance of the gold
amalgam is much stronger due to the formation of gold amalgam and the increase of
the nanoparticle surface area, leading to the decrease of the reduction time of 4
nitrophenol for the color change. This sensing system exhibits excellent
selectivity and ultrahigh sensitivity up to the 1.45 nM detection limit. The
practical use of this system for Hg(2+) determination in tap water samples is
also demonstrated successfully.
PMID- 26434977
TI - Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9
Epipolygodial against Drug-Resistant Cancer Cells.
AB - Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a
known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this
investigation a series of polygodial analogues were prepared and investigated for
TRPV1-agonist and anticancer activities. These experiments led to the
identification of 9-epipolygodial, which has antiproliferative potency
significantly exceeding that of polygodial. 9-Epipolygodial was found to maintain
potency against apoptosis-resistant cancer cells as well as those displaying the
multidrug-resistant (MDR) phenotype. In addition, the chemical feasibility for
the previously proposed mechanism of action of polygodial, involving the
formation of a Paal-Knorr pyrrole with a lysine residue on the target protein,
was demonstrated by the synthesis of a stable polygodial pyrrole derivative.
These studies reveal rich chemical and biological properties associated with
polygodial and its direct derivatives. These compounds should inspire further
work in this area aimed at the development of new pharmacological agents, or the
exploration of novel mechanisms of covalent modification of biological molecules
with natural products.
PMID- 26434981
TI - Peptide-Conjugated Gold Nanoprobe: Intrinsic Nanozyme-Linked Immunsorbant Assay
of Integrin Expression Level on Cell Membrane.
AB - Precisely quantifying the membrane protein expression level on cell surfaces is
of vital importance for early cancer diagnosis and efficient treatment. We
demonstrate that gold nanoparticle bioconjugated by a rationally designed peptide
as nanoprobe possesses selective labeling and accurate quantification capacity of
integrin GPIIb/IIIa on the human erythroleukemia cell line. Through selective
recognition and marking of integrin, two-photon photoluminescence of the
nanoprobe is exploited for direct observation of protein spatial distribution on
cell membrane. More importantly, utilizing intrinsic enzyme-like catalysis
property of the nanoprobe, the expression level of integrin on human
erythroleukemia cells can be quantitatively counted in an amplified and reliable
colorimetric assay without cell lysis and protein extraction process. In
addition, the analysis of the correlation between the gold nanoparticle and the
membrane protein via relevant inductively coupled plasma mass spectrometry
measurement verifies the reliability of the new analytical method. It is
anticipated that this facile and efficient strategy holds a great promise for a
rapid, precise, and reliable quantification of interested functional membrane
proteins on the cell surface.
PMID- 26434983
TI - The SR/ER-mitochondria calcium crosstalk is regulated by GSK3beta during
reperfusion injury.
PMID- 26434984
TI - Semiconductor-Insulator-Semiconductor Diode Consisting of Monolayer MoS2, h-BN,
and GaN Heterostructure.
AB - We propose a semiconductor-insulator-semiconductor (SIS) heterojunction diode
consisting of monolayer (1-L) MoS2, hexagonal boron nitride (h-BN), and epitaxial
p-GaN that can be applied to high-performance nanoscale optoelectronics. The
layered materials of 1-L MoS2 and h-BN, grown by chemical vapor deposition, were
vertically stacked by a wet-transfer method on a p-GaN layer. The final structure
was verified by confocal photoluminescence and Raman spectroscopy. Current
voltage (I-V) measurements were conducted to compare the device performance with
that of a more classical p-n structure. In both structures (the p-n and SIS
heterojunction diode), clear current-rectifying characteristics were observed. In
particular, a current and threshold voltage were obtained for the SIS structure
that was higher compared to that of the p-n structure. This indicated that
tunneling is the predominant carrier transport mechanism. In addition, the
photoresponse of the SIS structure induced by the illumination of visible light
was observed by photocurrent measurements.
PMID- 26434982
TI - Age-associated inflammation connects RAS-induced senescence to stem cell
dysfunction and epidermal malignancy.
AB - Aging is the single biggest risk factor for malignant transformation. Among the
most common age-associated malignancies are non-melanoma skin cancers, comprising
the most common types of human cancer. Here we show that mutant H-Ras activation
in mouse epidermis, a frequent event in cutaneous squamous cell carcinoma (SCC),
elicits a differential outcome in aged versus young mice. Whereas H-Ras
activation in the young skin results in hyperplasia that is mainly accompanied by
rapid hair growth, H-Ras activation in the aged skin results in more dysplasia
and gradual progression to in situ SCC. Progression is associated with increased
inflammation, pronounced accumulation of immune cells including T cells,
macrophages and mast cells as well as excessive cell senescence. We found not
only an age-dependent increase in expression of several pro-inflammatory
mediators, but also activation of a strong anti-inflammatory response involving
enhanced IL4/IL10 expression and immune skewing toward a Th2 response. In
addition, we observed an age-dependent increase in the expression of Pdl1,
encoding an immune suppressive ligand that promotes cancer immune evasion.
Moreover, upon switching off oncogenic H-Ras activity, young but not aged skin
regenerates successfully, suggesting a failure of the aged epidermal stem cells
to repair damaged tissue. Our findings support an age-dependent link between
accumulation of senescent cells, immune infiltration and cancer progression,
which may contribute to the increased cancer risk associated with old age.
PMID- 26434985
TI - The relationship between specific cognitive defects and burden of care in
Parkinson's disease.
AB - BACKGROUND: In spite of the recognized physical and psychosocial effects of
caring for patients with Parkinson's disease (PD), caregiver burden (CB) in this
setting is poorly understood. The objective of this research was to identify
factors that were associated with CB in an Australian population of PD caregivers
using a novel instrument - the Parkinson's Disease Caregiver Burden (PDCB)
questionnaire. METHODS: Fifty patient-caregiver couples were recruited from three
movement disorders clinics in Melbourne, Australia. Burden on caregivers was
rated using the PDCB questionnaire. Burden scores were correlated with patient
factors, including motor symptom severity (Unified Parkinson's Disease Ratings
Scale and Hoehn & Yahr (H&Y) scale), patient cognition (Neuropsychiatry Unit
Cognitive Assessment Tool; NUCOG), presence of impulsive and compulsive behaviors
(Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease), and
patient olfaction. Caregiver and patient demographics, as well as results for
depression and anxiety (Hospital Anxiety and Depression Scale; HADS), were also
examined for their relationship with CB. RESULTS: H&Y stage, depression or
anxiety in either caregiver or patient, and decreased patient NUCOG score were
significantly associated with higher PDCB score. Multiple linear regression
analysis identified caregiver and patient depression score and patient score for
the visuoconstructional subscale of NUCOG to predict burden score. In addition,
disease duration, duration of caregiving, and increased hours per day spent in
giving care were significantly associated with increased burden. CONCLUSIONS: We
found psychiatric and cognitive factors to be the most relevant factors in the
perception of burden in PD caregivers. On top of this, we found deficits in the
domain of visuoconstruction predicted burden - a relationship not yet described
in literature. Targeting depression and anxiety in this setting as well as
identifying caregivers at high risk of burden may give clinicians the chance to
optimize care of patients with PD through the caregiver.
PMID- 26434986
TI - Should an intercalated degree be compulsory for undergraduate medical students?
AB - Undertaking an intercalated year whilst at medical school involves taking time
out of the medicine undergraduate programme in order to pursue a separate but
related degree. It is widely seen as a challenging but rewarding experience, with
much to be gained from the independent project or research component of most
additional degrees. However, whilst intercalating is encouraged at many
universities and is incorporated into some undergraduate curricula, it is by no
means compulsory for all students. The literature would suggest that those who
have intercalated tend to do better academically, both for the remainder of
medical school and after graduating. Despite this, the issue of making
intercalation mandatory is one of considerable debate, with counter-arguments
ranging from the detrimental effect time taken out of the course can have to the
lack of options available to cater for all students. Nonetheless, the research
skills developed during an intercalated year are invaluable and help students
prepare for taking a critical evidence-based approach to medicine. If
intercalated degrees were made compulsory for undergraduates, it would be a step
in the right direction. It would mean the doctors of tomorrow would be better
equipped to practise medicine in disciplines that are constantly evolving.
PMID- 26434987
TI - Prediction of drug's Anatomical Therapeutic Chemical (ATC) code by integrating
drug-domain network.
AB - Predicting Anatomical Therapeutic Chemical (ATC) code of drugs is of vital
importance for drug classification and repositioning. Discovering new association
information related to drugs and ATC codes is still difficult for this topic. We
propose a novel method named drug-domain hybrid (dD-Hybrid) incorporating drug
domain interaction network information into prediction models to predict drug's
ATC codes. It is based on the assumption that drugs interacting with the same
domain tend to share therapeutic effects. The results demonstrated dD-Hybrid has
comparable performance to other methods on the gold standard dataset. Further,
several new predicted drug-ATC pairs have been verified by experiments, which
offer a novel way to utilize drugs for new purposes effectively.
PMID- 26434989
TI - [Migraine].
PMID- 26434988
TI - Role of Vasodilator Testing in Pulmonary Hypertension.
AB - Pulmonary hypertension is clinically defined by a mean pulmonary artery (PA)
pressure of 25mm Hg or more at rest, as measured by right heart catheterization.
To identify patients who are likely to have a beneficial response to calcium
channel blockers (CCBs) and therefore a better prognosis, acute vasodilator
testing should be performed in patients in certain subsets of pulmonary arterial
hypertension (PAH). A near normalization of pulmonary hemodynamics is needed
before patients can be considered for therapy with CCBs. Intravenous adenosine,
intravenous epoprostenol, inhaled nitric oxide, or inhaled iloprost are the
standard agents used for vasoreactivity testing in patients with idiopathic PAH.
In this review we describe the various aspects of vasodilator testing including
the rationale, pathophysiology and agents used in the procedure.
PMID- 26434990
TI - [Acute kidney injury in paracetamol poisoning].
PMID- 26434991
TI - [Diagnosis of nodular thyroid disease: An update].
PMID- 26434992
TI - [Systemic lupus erythematosus today].
PMID- 26434993
TI - Association of early and late maternal smoking during pregnancy with offspring
body mass index at 4 to 5 years of age.
AB - The objective was to investigate the association between early and late maternal
smoking during pregnancy on offspring body mass index (BMI). We undertook a
retrospective cohort study using linked records from the Women's and Children's
Health Network in South Australia. Among a cohort of women delivering a
singleton, live-born infants between January 2000 and December 2005 (n=7658),
5961 reported not smoking during pregnancy, 297 reported quitting smoking during
the first trimester of pregnancy, and 1400 reported continued smoking throughout
pregnancy. Trained nurses measured the height and weight of the children at
preschool visits in a state-wide surveillance programme. The main outcome measure
was age- and sex-specific BMI z-score. At 4 to 5 years, mean (s.d.) BMI z-score
was 0.40 (1.05), 0.60 (1.07) and 0.65 (1.18) in children of mothers who reported
never smoking, quitting smoking and continued smoking during pregnancy,
respectively. Compared with the group of non-smokers, both quitting smoking and
continued smoking were associated with an increase in child BMI z-score of 0.15
(95% confidence interval: 0.01-0.29) and 0.21 (0.13-0.29), respectively. A
significant dose-response relationship was also observed between the number of
cigarettes smoked per day on average during the second half of pregnancy and the
increase in offspring BMI z-score (P<0.001). In conclusion, any maternal smoking
in pregnancy, even if mothers quit, is associated with an increase in offspring
BMI at 4 to 5 years of age.
PMID- 26434994
TI - Nck1 deficiency improves pancreatic beta cell survival to diabetes-relevant
stresses by modulating PERK activation and signaling.
AB - Increasing evidence strongly supports a critical role for PERK in regulating
pancreatic beta cell function. In agreement, we previously reported that
enhancing PERK basal activity, by silencing the SH domain-containing adaptor
protein Nck1 in pancreatic beta cells, increased insulin content in a PERK
dependent manner. Here we report that Nck1-deficient MIN6 cells display normal
overall morphology while as expected increased number of secretory granules.
Furthermore, we demonstrate that cell survival to diabetes-relevant stresses is
increased, while cell viability in response to chemical endoplasmic reticulum
(ER) stress inducers is not changed. In agreement, PERK activation in Nck1
depleted MIN6 cells exposed to palmitate was significantly reduced while it
remained strongly induced by the ER stress inducer thapsigargin. Interestingly,
silencing Nck1 in MIN6 cells results in increased PERK basal activity and
expression of the PERK downstream target sestrin2, which promotes autophagy by
attenuating mTORC1 activation through AMPK-dependent and -independent mechanisms.
Accordingly, activated AMPK was increased, mTORC1 signaling decreased, and
autophagy markers increased in Nck1-silenced MIN6 cells. Increased autophagy was
recapitulated in Nck1(-/-) mice pancreatic beta cells. In addition, basal levels
of the PERK substrate Nrf2 and its antioxidant gene targets (HO-1 and Nqo1) were
upregulated in Nck1-silenced MIN6 cells, revealing an active PERK-Nrf2 signaling
in these cells. Finally, Akt activation was increased in Nck1-silenced MIN6
cells. Altogether, this study demonstrates that Nck1 silencing in pancreatic beta
cells promotes PERK activation and signaling to protect beta cells against
pathological stresses. These findings further provide new perspectives to advance
our understanding of molecular mechanisms and signaling systems regulating
pancreatic beta cell fates.
PMID- 26434996
TI - Dual regulation of energy metabolism by p53 in human cervix and breast cancer
cells.
AB - The role of p53 as modulator of OxPhos and glycolysis was analyzed in HeLa-L
(cells containing negligible p53 protein levels) and HeLa-H (p53-overexpressing)
human cervix cancer cells under normoxia and hypoxia. In normoxia, functional
p53, mitochondrial enzyme contents, mitochondrial electrical potential
(DeltaPsim) and OxPhos flux increased in HeLa-H vs. HeLa-L cells; whereas their
glycolytic enzyme contents and glycolysis flux were unchanged. OxPhos provided
more than 70% of the cellular ATP and proliferation was abolished by anti
mitochondrial drugs in HeLa-H cells. In hypoxia, both cell proliferations were
suppressed, but HeLa-H cells exhibited a significant decrease in OxPhos protein
contents, DeltaPsim and OxPhos flux. Although glycolytic function was also
diminished vs. HeLa-L cells in hypoxia, glycolysis provided more than 60% of
cellular ATP in HeLa-H cells. The energy metabolism phenotype of HeLa-H cells was
reverted to that of HeLa-L cells by incubating with pifithrin-alpha, a p53
inhibitor. In normoxia, the energy metabolism phenotype of breast cancer MCF-7
cells was similar to that of HeLa-H cells, whereas p53shRNAMCF-7 cells resembled
the HeLa-L cell phenotype. In hypoxia, autophagy proteins and lysosomes contents
increased 2-5 times in HeLa-H cells suggesting mitophagy activation. These
results indicated that under normoxia p53 up-regulated OxPhos without affecting
glycolysis, whereas under hypoxia, p53 down-regulated both OxPhos (severely) and
glycolysis (weakly). These p53 effects appeared mediated by the formation of p53
HIF-1alpha complexes. Therefore, p53 exerts a dual and contrasting regulatory
role on cancer energy metabolism, depending on the O2level.
PMID- 26434995
TI - Towards the molecular mechanism of the integration of peroxisomal membrane
proteins.
AB - The correct topogenesis of peroxisomal membrane proteins is a crucial step for
the formation of functioning peroxisomes. Although this process has been widely
studied, the exact mechanism with which it occurs has not yet been fully
characterized. Nevertheless, it is generally accepted that peroxisomes employ
three proteins - Pex3, Pex19 and Pex16 in mammals - for the insertion of
peroxisomal membrane proteins into the peroxisomal membrane. Structural biology
approaches have been utilized for the elucidation of the mechanistic questions of
peroxisome biogenesis, mainly by providing information on the architecture of the
proteins significant for this process. This review aims to summarize, compare and
put into perspective the structural knowledge that has been generated mainly for
Pex3 and Pex19 and their interaction partners in recent years.
PMID- 26434997
TI - Peroxisome homeostasis: Mechanisms of division and selective degradation of
peroxisomes in mammals.
AB - Peroxisome number and quality are maintained by its biogenesis and turnover and
are important for the homeostasis of peroxisomes. Peroxisomes are increased in
number by division with dynamic morphological changes including elongation,
constriction, and fission. In the course of peroxisomal division, peroxisomal
morphogenesis is orchestrated by Pex11beta, dynamin-like protein 1 (DLP1), and
mitochondrial fission factor (Mff). Conversely, peroxisome number is reduced by
its degradation. Peroxisomes are mainly degraded by pexophagy, a type of
autophagy specific for peroxisomes. Upon pexophagy, an adaptor protein
translocates on peroxisomal membrane and connects peroxisomes to autophagic
machineries. Molecular mechanisms of pexophagy are well studied in yeast systems
where several specific adaptor proteins are identified. Pexophagy in mammals also
proceeds in a manner dependent on adaptor proteins. In this review, we address
the recent progress in studies on peroxisome morphogenesis and pexophagy.
PMID- 26434998
TI - The risks and benefits of disclosing psychotherapy records to the legal system:
What psychologists and patients need to know for informed consent.
AB - When psychologists release patient records to the legal system, the typical
practice is to obtain the patient's signature on a consent form, but rarely is a
formal informed-consent obtained from the patient. Although psychologists are
legally and ethically required to obtain informed consent for all services
(including disclosure of records), there are a number of barriers to obtaining
truly informed consent. Furthermore, compared to disclosures to nonlegal third
parties, there are significantly greater risks when records are disclosed to the
legal system. For these reasons, true informed consent should be obtained from
the patient when records are disclosed to the legal system. A model for informed
consent is proposed. This procedure should include a description of risks and
benefits of disclosing or refusing to disclose by the psychotherapist, an
opportunity to ask questions, and indication by the patient of a freely made
choice. Both psychotherapist and patient share decision making responsibilities
in our suggested model. The patient should be informed about potential harm to
the therapeutic relationship, if applicable. Several recommendations for practice
are described, including appropriate communications with attorneys and the legal
system. A sample form, for use by psychotherapists, is included.
PMID- 26434999
TI - Development and in vitro assessment of alginate bilayer films containing the
olive compound hydroxytyrosol as an alternative for topical chemotherapy.
AB - Topical chemotherapy is the application of cancer drugs directly onto the skin,
which has become a standard treatment for basal cell carcinoma. Due to the
promising results in the treatment of skin cancer, topical chemotherapy has
recently been applied to breast cancer patients because some breast cancer
tissues are only superficial. Hydroxytyrosol, a phenolic compound from olives
that is present in high amounts in Hidrox((r)) olive extract, has been shown to
have a protective effect on normal cells and selective antitumor activities on
cancerous cells. The aims of the present study were to develop an alginate
bilayer film containing Hidrox((r)) and to investigate its potential use as a
topical chemotherapeutic agent. Alginate films were characterized for swelling
and for physical, thermal, rheological, and mechanical properties. Drug content
uniformity and in vitro drug release tests were also investigated. The alginate
bilayer films containing Hidrox((r)), HB2, showed controlled release of
hydroxytyrosol at a flux of 0.094+/-0.009 mg/cm(2)/h. The results of the
cytotoxic assay showed that the HB2 films were dose-dependent and could
significantly reduce the growth of breast cancer cells (MCF-7) at 150 MUg/mL for
a cell viability of 29.34+/-4.64%. In conclusion, an alginate bilayer film
containing Hidrox((r)) can be a potential alternative for topical
chemotherapeutic agent for skin and breast cancer treatment.
PMID- 26435000
TI - Chlorpyrifos induces NLRP3 inflammasome and pyroptosis/apoptosis via
mitochondrial oxidative stress in human keratinocyte HaCaT cells.
AB - Chlorpyrifos (CPF) has been widely used around the world as a pesticide for both
agricultural and residential application. Although various studies have reported
toxicity and health-related effects from CPF exposure, the molecular mechanism of
CPF toxicity to skin has not been well-characterized. The present study
determined the potential mechanism involved in skin toxicity of CPF using the
HaCaT human skin keratinocyte cell line. After treating to HaCaT cells, CPF
triggered reactive oxygen species (ROS) generation and mitochondrial oxidative
stress. We focused on NLRP3 inflammasome, known to induce innate immune response.
We used mitochondrial ROS (mROS) scavenger mitoTEMPO to demonstrate a role for
mROS in NLRP3 inflammasome and programmed cell death induced by CPF. Our results
showed that CPF provoked NLRP3 inflammasome and pyroptosis/apoptosis via an
increase of mROS in HaCaT cells. This study proposes that CPF induces innate
immune response and skin inflammation through activating the NLRP3 inflammasome
in skin epithelial cells. CPF may lead to cutaneous disease conditions and
antioxidants could be proposed for therapy against skin exposure to CPF.
PMID- 26435001
TI - Bisphenol AF stimulates transcription and secretion of C-X-C chemokine ligand 12
to promote proliferation of cultured T47D breast cancer cells.
AB - Bisphenol AF (4,4'-hexafluoroisopropylidene-2-diphenol, BPAF), an endocrine
disruptor, has been shown to stimulate the proliferation of human breast cancer
cells. However, the underlying mechanism has not been fully elucidated. We found
that BPAF promoted the in vitro proliferation of estrogen receptor alpha
(ERalpha)-positive breast cancer cells (T47D and MCF7), but not ERalpha-negative
cells (MDA-MB-231 and MDA-MB-435s). BPAF significantly stimulated the
proliferation of cultured T47D cell in a dose-dependent manner, and the half
maximal effective concentration (EC50) was approximately 123 nM. We employed
lentivirus-mediated short hairpin RNA (shRNA) to knockdown ERalpha and ER
antagonist ICI 182780 to inhibit ER activation, which resulted in the repression
of BPAF-induced proliferation of T47D and MCF7 cells. We observed that C-X-C
chemokine ligand 12 (CXCL12) was up-regulated in T47D cells under treatment with
BPAF. Quantitative real-time PCR results showed that BPAF caused a time and dose
dependent increase in mRNA level of CXCL12. Furthermore, treatment of T47D cells
with BPAF increased CXCL12 secretion according to ELISA assay. BPAF-induced
CXCL12 transcription and secretion was significantly attenuated by small
interfering RNA (siRNA) targeting ERalpha and ICI 182780, indicating BPAF-induced
CXCL12 expression is mediated through ERalpha. Notably, knockdown CXCL12 in T47D
cells significantly attenuated BPAF-induced cell proliferation. We also observed
that inhibition of CXCL12 binding to its receptors CXCR4 and CXCR7 by chalcone 4
blocked BPAF-induced cell growth. Our results indicated that CXCL12 facilitated
BPAF-induced proliferation of T47D cells. Taken together, our data provided
support that BPAF stimulated transcription and secretion of CXCL12 depending on
ERalpha, and ERalpha/CXCL12 signaling positively regulated BPAF-induced
proliferation of cultured T47D breast cancer cells.
PMID- 26435002
TI - Horizontal gene transfer of a Chlamydial tRNA-guanine transglycosylase gene to
eukaryotic microbes.
AB - tRNA-guanine transglycosylases are found in all domains of life and mediate the
base exchange of guanine with queuine in the anticodon loop of tRNAs. They can
also regulate virulence in bacteria such as Shigella flexneri, which has prompted
the development of drugs that inhibit the function of these enzymes. Here we
report a group of tRNA-guanine transglycosylases in eukaryotic microbes (algae
and protozoa) which are more similar to their bacterial counterparts than
previously characterized eukaryotic tRNA-guanine transglycosylases. We provide
evidence demonstrating that the genes encoding these enzymes were acquired by
these eukaryotic lineages via horizontal gene transfer from the Chlamydiae group
of bacteria. Given that the S. flexneri tRNA-guanine transglycosylase can be
targeted by drugs, we propose that the bacterial-like tRNA-guanine
transglycosylases could potentially be targeted in a similar fashion in
pathogenic amoebae that possess these enzymes such as Acanthamoeba castellanii.
This work also presents ancient prokaryote-to-eukaryote horizontal gene transfer
events as an untapped resource of potential drug target identification in
pathogenic eukaryotes.
PMID- 26435003
TI - Molecular phylogeny reveals genital convergences and reversals in the barklouse
genus Trichadenotecnum (Insecta: Psocodea: 'Psocoptera': Psocidae).
AB - Trichadenotecnum is one of the most diverse genera among the non-parasitic
members of Psocodea (Insecta: "Psocoptera"). The genus shows a world-wide
distribution (excluding the Australian Region, where only one introduced species
is known) with its center of diversity in southern to eastern Asia. Several
species groups had been proposed for this large genus based on morphology, but
their validity and phylogenetic relationships are still unclear because of great
morphological diversity in the genitalia, systematically the most relevant
character. In this study, we estimated the molecular phylogeny of the Old World
species of Trichadenotecnum based on extensive taxon sampling. As a result, the
monophyly of morphology-based species groups was very strongly supported in most
cases. However, two groups were recovered as non-monophyletic, which had been
inadequately defined on the basis of plesiomorphies or convergences of genital
characters. First, the monophyly of the sexpunctatum group was not supported
because the medium group was found to be embedded within this group. The simpler
genitalia observed in the medium group were considered to be derived from the
more complicated genitalia present in the sexpunctatum group. Second, the
monophyly of the majus group was not supported for two reasons: (1) It was
divided into two distant clades which initially had been united on the basis of
convergent similarities of the male genitalia. (2) Two species groups were
revealed to be embedded within the main clade of the majus group; the initial
separation of these groups had been based on reversals to the ancestral genital
condition.
PMID- 26435005
TI - Clinical characteristics and genotype-phenotype correlations in C3 deficiency.
PMID- 26435006
TI - Menopause as a predictor of new-onset asthma: A longitudinal Northern European
population study.
AB - BACKGROUND: There is limited and conflicting evidence on the effect of menopause
on asthma. OBJECTIVES: We sought to study whether the incidence of asthma and
respiratory symptoms differ by menopausal status in a longitudinal population
based study with an average follow-up of 12 years. METHODS: The Respiratory
Health in Northern Europe study provided questionnaire data pertaining to
respiratory and reproductive health at baseline (1999-2001) and follow-up (2010
2012). The study cohort included women aged 45 to 65 years at follow-up, without
asthma at baseline, and not using exogenous hormones (n = 2322). Menopausal
status was defined as nonmenopausal, transitional, early postmenopausal, and late
postmenopausal. Associations with asthma (defined by the use of asthma
medication, having asthma attacks, or both) and respiratory symptoms scores were
analyzed by using logistic (asthma) and negative binomial (respiratory symptoms)
regressions, adjusting for age, body mass index, physical activity, smoking,
education, and study center. RESULTS: The odds of new-onset asthma were increased
in women who were transitional (odds ratio, 2.40; 95% CI, 1.09-5.30), early
postmenopausal (odds ratio, 2.11; 95% CI, 1.06-4.20), and late postmenopausal
(odds ratio, 3.44; 95% CI, 1.31-9.05) at follow-up compared with nonmenopausal
women. The risk of respiratory symptoms increased in early postmenopausal
(coefficient, 0.40; 95% CI, 0.06-0.75) and late postmenopausal (coefficient,
0.69; 95% CI, 0.15-1.23) women. These findings were consistent irrespective of
smoking status and across study centers. CONCLUSIONS: New-onset asthma and
respiratory symptoms increased in women becoming postmenopausal in a longitudinal
population-based study. Clinicians should be aware that respiratory health might
deteriorate in women during reproductive aging.
PMID- 26435004
TI - Protein disulfide isomerase-endoplasmic reticulum resident protein 57 regulates
allergen-induced airways inflammation, fibrosis, and hyperresponsiveness.
AB - BACKGROUND: Evidence for association between asthma and the unfolded protein
response is emerging. Endoplasmic reticulum resident protein 57 (ERp57) is an
endoplasmic reticulum-localized redox chaperone involved in folding and secretion
of glycoproteins. We have previously demonstrated that ERp57 is upregulated in
allergen-challenged human and murine lung epithelial cells. However, the role of
ERp57 in asthma pathophysiology is unknown. OBJECTIVES: Here we sought to examine
the contribution of airway epithelium-specific ERp57 in the pathogenesis of
allergic asthma. METHODS: We examined the expression of ERp57 in human asthmatic
airway epithelium and used murine models of allergic asthma to evaluate the
relevance of epithelium-specific ERp57. RESULTS: Lung biopsy specimens from
asthmatic and nonasthmatic patients revealed a predominant increase in ERp57
levels in epithelium of asthmatic patients. Deletion of ERp57 resulted in a
significant decrease in inflammatory cell counts and airways resistance in a
murine model of allergic asthma. Furthermore, we observed that disulfide bridges
in eotaxin, epidermal growth factor, and periostin were also decreased in the
lungs of house dust mite-challenged ERp57-deleted mice. Fibrotic markers, such as
collagen and alpha smooth muscle actin, were also significantly decreased in the
lungs of ERp57-deleted mice. Furthermore, adaptive immune responses were
dispensable for house dust mite-induced endoplasmic reticulum stress and airways
fibrosis. CONCLUSIONS: Here we show that ERp57 levels are increased in the airway
epithelium of asthmatic patients and in mice with allergic airways disease. The
ERp57 level increase is associated with redox modification of proinflammatory,
apoptotic, and fibrotic mediators and contributes to airways hyperresponsiveness.
The strategies to inhibit ERp57 specifically within the airways epithelium might
provide an opportunity to alleviate the allergic asthma phenotype.
PMID- 26435008
TI - Recent advances in clay mineral-containing nanocomposite hydrogels.
AB - Clay mineral-containing nanocomposite hydrogels have been proven to have
exceptional composition, properties, and applications, and consequently have
attracted a significant amount of research effort over the past few years. The
objective of this paper is to summarize and evaluate scientific advances in clay
mineral-containing nanocomposite hydrogels in terms of their specific
preparation, formation mechanisms, properties, and applications, and to identify
the prevailing challenges and future directions in the field. The state-of-the
art of existing technologies and insights into the exfoliation of layered clay
minerals, in particular montmorillonite and LAPONITE(r), are discussed first. The
formation and structural characteristics of polymer/clay nanocomposite hydrogels
made from in situ free radical polymerization, supramolecular assembly, and
freezing-thawing cycles are then examined. Studies indicate that additional
hydrogen bonding, electrostatic interactions, coordination bonds, hydrophobic
interaction, and even covalent bonds could occur between the clay mineral
nanoplatelets and polymer chains, thereby leading to the formation of unique
three-dimensional networks. Accordingly, the hydrogels exhibit exceptional
optical and mechanical properties, swelling-deswelling behavior, and stimuli
responsiveness, reflecting the remarkable effects of clay minerals. With the
pivotal roles of clay minerals in clay mineral-containing nanocomposite
hydrogels, the nanocomposite hydrogels possess great potential as
superabsorbents, drug vehicles, tissue scaffolds, wound dressing, and biosensors.
Future studies should lay emphasis on the formation mechanisms with in-depth
insights into interfacial interactions, the tactical functionalization of clay
minerals and polymers for desired properties, and expanding of their
applications.
PMID- 26435007
TI - Women's work in farming, child feeding practices and nutritional status among
under-five children in rural Rukwa, Tanzania.
AB - Some progress has been achieved in reducing the prevalence of undernutrition
among children under 5 years of age in Tanzania. In the Rukwa region (2010), the
level of stunted and underweight children was 50.4 and 13.5 %, respectively. The
aim of this study was to assess the nutritional status of children under 5 years
of age, feeding practices and risk factors of undernutrition in a rural village
in the Rukwa region, as well as to discuss the results in light of a similar
study conducted in 1987/1988. This cross-sectional study was conducted in 152
households with children under 5 years of age. Data were obtained from the
child's main caretaker and the household head, using a structured questionnaire
and a 24 h dietary recall. Children's length/height and weight were measured. The
prevalence of stunting and underweight was found to be 63.8 and 33.6 % (Z-score<
2 of WHO 2006 CGS), respectively. Sugar-water was given to 72.3 % of the children
on the first day after birth. A thin gruel was introduced after a median of 2
months (25th-75th percentiles; 1-3). The time mothers spent farming was a
significant risk factor for stunting (P=0.04). Illness, food shortage and dry
season cultivation were significant risk factors for underweight (P<0.01). Using
the NCHS/WHO 1983 growth reference (<75 % of the median), the prevalence of
underweight was 25.0 %, similar to that reported in 1987/1988 (26.4 %). In
conclusion, the underweight prevalence was found to be at the same level in 2010
as was recorded in 1987/1988. Current child-feeding practices were not in line
with WHO recommendations. Women working in farms, food shortage, dry-season
cultivation and diseases partly explain the children's poor nutritional status.
PMID- 26435009
TI - Persistent alterations in active and passive electrical membrane properties of
regenerated nerve fibers of man and mice.
AB - Excitability of regenerated fibers remains impaired due to changes in both
passive cable properties and alterations in the voltage-dependent membrane
function. These abnormalities were studied by mathematical modeling in human
regenerated nerves and experimental studies in mice. In three adult male patients
with surgically repaired complete injuries of peripheral nerves of the arm 22
months-26 years prior to investigation, deviation of excitability measures was
explained by a hyperpolarizing shift in the resting membrane potential and an
increase in the passive 'Barrett and Barrett' conductance (GBB) bridging the
nodal and internodal compartments. These changes were associated with an increase
in the 'fast' K(+) conductance and the inward rectifier conductance (GH). Similar
changes were found in regenerated mouse tibial motor axons at 1 month after a
sciatic crush lesion. During the first 5 months of regeneration, GH showed
partial recovery, which paralleled that in GBB. The internodal length remained
one-third of normal. Excitability abnormalities could be reversed by the energy
dependent Na(+)/K(+) pump blocker ouabain resulting in membrane depolarization.
Stressing the Na(+) pumping system during a strenuous activity protocol triggered
partial Wallerian degeneration in regenerated nerves but not in control nerves
from age-matched mice. The current data suggest that the nodal voltage-gated ion
channel machinery is restored in regenerated axons, although the electrical
separation from the internodal compartment remains compromised. Due to the
persistent increase in number of nodes, the increased activity-dependent Na(+)
influx could lead to hyperactivity of the Na(+)/K(+) pump resulting in membrane
hyperpolarization and neurotoxic energy insufficiency during strenuous activity.
PMID- 26435010
TI - The electronic structures of group-V-group-IV hetero-bilayer structures: a first
principles study.
AB - Recent findings of group-V nanosheets provide new building units for van der
Waals hetero-nanostructures. Based on first-principles calculation, we
investigate the structural and electronic properties of bilayer hetero-sheets
composed of group-V (arsenene/antimonene) and group-IV (graphene/silicene)
layers. These hetero-sheets exhibit typical van der Waals features with small
binding energies and soft interlayer elastic constants. In the hetero-sheets, the
Dirac characteristics of the group-IV layer and the semiconducting feature of the
group-V one are well preserved, which causes a Schottky contact at the metal
semiconductor interface. The Schottky barriers are always p-type in the Si-based
hetero-sheets, whereas in the C-based ones, the interfacial feature is sensitive
to the interlayer distance. A tensile strain would induce a p-type-to-n-type
Schottky barrier transition for the As-C hetero-sheet, while a compressive strain
can cause a Schottky-to-ohmic contact transition in the Sb-C one. Moreover, due
to the inhomogeneous charge redistribution, a sizeable band gap is opened at the
Dirac point of the Sb-Si hetero-sheet, which could be linearly modulated by
perpendicular strains around the equilibrium site. The versatile electronic
structures and tunable interfacial properties enable the group-V-group-IV hetero
bilayer structures to have many potential applications in nano-devices and nano
electronics.
PMID- 26435011
TI - Highly active self-immobilized FI-Zr catalysts in a PCP framework for ethylene
polymerization.
AB - A series of zirconium-based porous coordination polymers (PCPs) containing FI
catalysts in the frameworks have been developed and studied as catalysts for
ethylene polymerization. These PCPs exhibit good catalytic activities and long
life times, producing polyethylenes with high molecular weights and bimodal
molecular weight distribution in the form of particles.
PMID- 26435014
TI - The perspective of caffeine and caffeine derived compounds in therapy.
AB - Caffeine (1,3,7-trimethylxanthine) is a plant secondary metabolite with a
significant impact on multiple processes and regulatory pathways in the body.
Though major part of the population meets caffeine via coffee, tea or chocolate,
it has also an important role in pharmacology and it is used as a supplementary
substance in medicaments. Currently, the ability of caffeine to ameliorate some
neurodegenerative disorders is proved in some studies. This review describes
basic data about caffeine including toxicity, pharmacokinetics, biological
mechanism of the action, and metabolism. Beside this, promising applications of
caffeine, new medicaments and derivatives are discussed. Relevant papers and
inventions are depicted in the manuscript. Caffeine is a pharmacologically
promising substance that deserves big consideration in the current research and
development. The compound has several reasons to be an object of scientific
interest and to be used for pharmacology purposes. Despite an extensive research
for a long time, no significantly negative effects on human health were proved
hence caffeine can be considered as a completely safe compound. The recent data
about amelioration of neurodegenerative and other disorders are promising and
deserving more work on the issue. ARTICLE HIGHLIGHTS: Caffeine is a purine
alkaloid from plants and it has a broad use in current pharmacology. Caffeine is
a competitive antagonist of neurotransmitter adenosine on adenosine receptors.
The substance is added as a supplementary to drugs and food.Besides interfering
on adenosine receptors, caffeine interacts with acetylcholinesterase, monoamine
oxidase, phosphodiesterase, ryanodine receptors and others.Current research is
devoted to the role of caffeine in neurodegenerative diseases and immunity
alteration. New chemical compounds based on caffeine moiety are prepared (Tab. 4,
Fig. 6, Ref. 149).
PMID- 26435015
TI - Physician-Pharmacist collaboration in a pay for performance healthcare
environment.
AB - Healthcare is becoming more complex and costly in both European (Slovak) and
American models. Healthcare in the United States (U.S.) is undergoing a
particularly dramatic change. Physician and hospital reimbursement are becoming
less procedure focused and increasingly outcome focused. Efforts at Mercy
Hospital have shown promise in terms of collaborative team based care improving
performance on glucose control outcome metrics, linked to reimbursement. Our
performance on the Centers for Medicare and Medicaid Services (CMS) post
operative glucose control metric for cardiac surgery patients increased from a
63.6% pass rate to a 95.1% pass rate after implementing interventions involving
physician-pharmacist team based care.Having a multidisciplinary team that is able
to adapt quickly to changing expectations in the healthcare environment has aided
our institution. As healthcare becomes increasingly saturated with technology,
data and quality metrics, collaborative efforts resulting in increased quality
and physician efficiency are desirable. CONCLUSION: Multidisciplinary
collaboration (including physician-pharmacist collaboration) appears to be a
viable route to improved performance in an outcome based healthcare system (Fig.
2, Ref. 12).
PMID- 26435012
TI - EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure:
potential role of free fatty acid receptor 4.
AB - Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but
standard HF therapies are ineffective. Diastolic dysfunction, often secondary to
interstitial fibrosis, is common in HFpEF. Previously, we found that supra
physiologic levels of omega3-PUFAs produced by 12 weeks of omega3-dietary
supplementation prevented fibrosis and contractile dysfunction following pressure
overload [transverse aortic constriction (TAC)], a model that resembles aspects
of remodeling in HFpEF. This raised several questions regarding omega3
concentration-dependent cardioprotection, the specific role of EPA and DHA, and
the relationship between prevention of fibrosis and contractile dysfunction. To
achieve more clinically relevant omega3-levels and test individual omega3-PUFAs,
we shortened the omega3-diet regimen and used EPA- and DHA-specific diets to
examine remodeling following TAC. The shorter diet regimen produced omega3-PUFA
levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis
following TAC. However, neither omega3-PUFA prevented contractile dysfunction,
perhaps due to reduced uptake of omega3-PUFA. Interestingly, EPA did not
accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled
receptor for omega3-PUFAs, was sufficient and required to block transforming
growth factor beta1-fibrotic signaling in cultured cardiac fibroblasts,
suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of
fibrosis could represent a novel therapy for HFpEF.
PMID- 26435013
TI - Orienting Toward Face-Like Stimuli in Early Childhood.
AB - Newborn infants orient preferentially toward face-like or "protoface" stimuli and
recent studies suggest similar reflexive orienting responses in adults. Little is
known, however, about the operation of this mechanism in childhood. An
attentional-cueing procedure was therefore developed to investigate protoface
orienting in early childhood. Consistent with the extant literature, 5- to 6-year
old children (n = 25) exhibited orienting toward face-like stimuli; they
responded faster when target location was cued by the appearance of a protoface
stimulus than when location was cued by matched control patterns. The potential
of this procedure to investigate the development of typical and atypical social
perception is discussed.
PMID- 26435016
TI - More risk factors generate lower mortality--a useful advice for improved health
in the world.
PMID- 26435017
TI - The use of antiplatelet medication in hospitalised elderly patients.
AB - BACKGROUND: The use of antiplatelet agents is strongly recommended for the
secondary prevention of ischemic events such as myocardial infarction,
stroke/transient ischemic attack (TIA). OBJECTIVES: The aim of our study was to
analyse the use of antiplatelet medication in patients after myocardial
infarction, stroke/TIA, and patients with both conditions and to identify patient
related characteristics, which determine the use of such drugs in elderly
patients. METHODS: Study sample (n=372) was derived from 2,157 patients admitted
to long-term care departments of three municipal hospitals. The study included
patients aged >=65 years after myocardial infarction, stroke/TIA or both.
RESULTS: Antiplatelet medications were prescribed in 54.8 % and 68.5 % of
patients at hospital admission and discharge, respectively. Hospitalisation led
to a significant increase in the use of antiplatelet medication in patients after
myocardial infarction and in those with the combination of both events. However,
in patients after only stroke/TIA, we did not find any significant difference
comparing the use of antiplatelet medication at the time of hospital admission
and discharge, respectively. CONCLUSION: Our study revealed that physicians are
more aware of the benefits of antiplatelet medication in elderly patients after
myocardial infarction or those after both myocardial infarction and stroke/TIA in
comparison with patients after only stroke/TIA (Tab. 3, Ref. 32).
PMID- 26435018
TI - Surgical treatment of hepatocellular carcinoma.
AB - The incidence of hepatocellular carcinoma (HCC) in Europe and throughout the
world is currently increasing. This is caused by an increase in the number of
patients with alcoholic liver damage, metabolic syndrome, and by increasing
incidence of hepatitis B and C.From January 1, 2004 to December 31, 2013,
resection or radiofrequency ablation of the liver was done in 360 patients with
benign lesions or malignant tumors of the liver. In 28 patients HCC was diagnosed
and histologically confirmed (7.8 %). Seven patients had HCC associated with
liver cirrhosis (25 %), and 21 patients were without histologically confirmed
cirrhosis (75 %). R0 resection was done in 18 (64 %) patients.Surgical
complications occurred in 6 (21 %) patients and reoperation due to tumor relapse
or progression was done eight times in 6 (21 %) patients. One-year and five-year
patients' survivals were 64 % and 10 %, repectively, and did not statistically
differ from the survival of the whole set of patients with tumor diseases in the
given time period. In the future it will be possible to improve the long-term
survival of patients with HCC by using screening methods for presymptomatic
diagnosis of HCC, precise preoperative diagnosis and efforts for R0 resection
(Tab. 1, Fig. 4, Ref. 11).
PMID- 26435019
TI - Preimplantation genetic diagnosis of X-linked diseases examined by indirect
linkage analysis.
AB - BACKGROUND: Many centers of assisted reproduction in the Czech Republic offer
preimplantation genetic diagnosis with fluorescent in situ hybridization (FISH)
to couples requiring preimplantation genetic diagnosis (PGD) of X-linked
diseases. However, this process results in discarding all male embryos and is not
able to distinguish a carrier or healthy female embryo in X-linked recessive
disorders. OBJECTIVES: The main aim of this study was to summarize a six-year
period of PGD of X-linked monogenic diseases using indirect linkage analysis.
METHODS AND RESULTS: We wanted to accentuate the advantage indirect analysis of
PGD using multiple displacement amplification (MDA) followed by short tandem
repeat (STR) analysis. We present forty-six PGD cycles, including pre-case
haplotyping (PGH) panel, for fifteen X-linked diseases. Embryo transfer was made
thirty-eight times and gravidity was confirmed in thirteen female probands with a
success rate of pregnancy calculated at 42 %. CONCLUSIONS: PGD procedure using
MDA amplification followed by STR analysis provides help in identifying genetic
defects within embryos prior to implantation. The reliability of the method was
also supported by high pregnancy rate compared to other publications, which
commonly achieved a 30-35 % success rate (Tab. 2, Fig. 1, Ref. 33).
PMID- 26435020
TI - Petroselinum crispum extract attenuates hepatic steatosis in rats fed with
fructose enriched diet.
AB - Non alcoholic fatty liver disease (NAFLD) is the most common chronic liver
disease and ongoing research efforts are focused on understanding the underlying
pathophysiology of hepatic steatosis with the anticipation that these efforts
will identify novel therapeutic targets. This study investigated the Petroselinum
crispum extract in hepatic steatosis in rats fed with fructose enriched diet.
Rats were divided into the 4 groups: Group 1 rats received standard pellet diet
with corn starch for the entire experimental period of 8 weeks. Group 2 rats
received standard pellet diet and 2 gm/kg body weight crude Parsley leaf ethanol
extract for the entire experimental period of 8 weeks. Group 3 rats received
modified fructose diet. Group 4 rats received modified fructose diet and 2gm/kg
crude Parsley leaf ethanol extract. Hepatic function and structure was evaluated
in these rats. Modified fructose diet produced dyslipidemia, hepatic steatosis
and infiltration of inflammatory cells in the liver and higher plasma hepatic
markers. Petroselinum crispum extract reversed metabolic changes such as abnormal
crispum extract attenuated chronic changes in modified fructose diet induced
NAFLD (Tab. 2, Fig. 3, Ref. 43).
PMID- 26435021
TI - Effect of sinapic acid on 1,2 dimethylhydrazine induced aberrant crypt foci,
biotransforming bacterial enzymes and circulatory oxidative stress status in
experimental rat colon carcinogenesis.
AB - AIM: This study was aimed to investigate the effect of sinapic acid (SA) on 1,2
dimethylhydrazine (DMH) induced experimental rat colon carcinogenesis. MATERIALS
AND METHODS: Rats were assorted into six groups, group 1 served as control, group
2 received SA (80 mg/kg b.w.) post orally every day until the end of the
experimental period of 16 weeks, groups 3-6 rats were injected DMH (20 mg/kg
b.w.) subcutaneously once a week for first four weeks. In addition, groups 4-6
rats received different doses of SA (20, 40 and 80 mg/kg b.w.). RESULTS: Our
results showed that DMH induced rats revealed significantly increased ACF
development and multiplicity, which were significantly inhibited on
supplementation with SA. Moreover, elevated levels/activities of circulatory
oxidative stress markers, faecal and colonic mucosal bacterial enzymes were
observed in DMH exposed rats, which were diminished on supplementation with SA.
CONCLUSION: Overall, our findings revealed that supplementation with SA offers
significant protection against DMH induced rat colon carcinogenesis and the
effect of SA at the dose of 40 mg/kg b.w. was more pronounced as compared to the
other two doses. (Tab.5, Fig. 3, Ref. 46)
PMID- 26435022
TI - The role of mitochondrial ATP-sensitive potassium channels on cardiovascular
effects of thiopental and ketamine in rats.
AB - OBJECTIVE: We aimed to investigate whether mitochondrial ATP-sensitive potassium
(mitoKATP) channels play any role on cardiovascular effects of thiopental (TP) or
ketamine (K) anesthesia in rats. BACKGROUND: mitoKATP channels are the end
effectors of cardioprotection induced by some anesthetics. TP and K are the most
frequently used anesthetics with their own cardiovascular effects in experimental
studies. To the best of our knowledge, there is no study investigating the
cardiovascular effects of TP and K associated with mitoKATP channels. MATERIALS
AND METHODS: The experimental groups: TP control, K/Xylazine (X) control, TP+5
hydroxydecanoate (5-HD; mitoKATP channel blocker) and K/X+5-HD. Mean arterial
blood pressure (MABP), heart rate (HR) and standard limb lead II ECG were
recorded and arrhythmia parameters were evaluated. RESULTS: Blockage of mitoKATP
channels by 5-HD increased MABP and decreased HR in the TP+5-HD and K/X+5-HD
groups, respectively. 5-HD caused an increase in ventricular ectopic beat (VEB)
incidence. Moreover, VEB incidence was significantly different in TP+5-HD (100%)
than K/X+5-HDgroup (66.6%) and ventricular tachycardia was only seen in TP+5-HD
(incidence was 88.3%). CONCLUSION: mitoKATP channels play different roles in
influencing cardiovascular effects of K/X and TP anesthesia in rats. The
differences in hemodynamic parameters and arrhythmia scores of these anesthetics
should be considered when they are used in an experimental study associated with
mitoKATP channels (Fig. 3, Ref. 35).
PMID- 26435023
TI - Continuous epidural analgesia, a new prospect in analgesia of newborns.
AB - The popularity of continuous caudal epidural block in post-operative analgesia in
very young children has been growing. This method of analgesia is used in major
abdominal and urological surgeries. A local anaesthetic, usually levobupivacaine,
is administered through an epidural catheter introduced via hiatus canalis
sacralis. The usual type of the catheter is Arrow G20 armed with a metal spiral,
which can be used for children of up to approximately 2000 g of body weight. We
want to introduce a modification of the method which uses the thin silicone
catheter Premicath G28. This catheter allows for the administration of caudal
epidural analgesia even in premature children of approximately 500 g of body
weight. This solution eliminates adverse effects of systemic opioid analgesia,
accelerates surgical wound healing and disconnection from ventilation system, and
improves the potential of enteral nutrition. Depth and quality of analgesia in
very young children are monitored using a complex scheme called Comfort Neo Scale
(Tab. 1, Fig. 2, Ref. 7).
PMID- 26435024
TI - Extremely rare tumour--malignant mesothelioma of tunica vaginalis testis.
AB - INTRODUCTION: Malignant mesothelioma of tunica vaginalis testis is an extremely
rare tumour. It is often caused by exposition to asbestos, however, more often
its occurrence is sporadic. The diagnosis is usually set secondarily during
hydrocele surgery. This type of tumour should be considered in cases with with
atypical hydrocele, especially haematocele or atypical shape of seminal covering.
RESULTS: A case of an asbestos-exposed patient with described disease and long
term hydrocele is presented. The number of patients is so small that the
guidelines are limited due to low statistical power (Fig. 2, Ref. 14).
PMID- 26435025
TI - Prokineticin 2 facilitates mechanical allodynia induced by alpha,beta-methylene
ATP in rats.
AB - Prokineticin 2 (PK2), a new chemokine, causes mechanical hypersensitivity in the
rat hind paw, but little is known about the molecular mechanism. Here, we have
found that ionotropic P2X receptor is essential to mechanical allodynia induced
by PK2. First, intraplantar injection of high dose (3 or 10 pmol) of PK2
significantly increased paw withdrawal response frequency (%) to innocuous
mechanical stimuli (mechanical allodynia). And the mechanical allodynia induced
by PK2 was prevented by co-administration of TNP-ATP, a selective P2X receptor
antagonist. Second, although low dose (0.3 or 1 pmol) of PK2 itself did not
produce an allodynic response, it significantly facilitated the mechanical
allodynia evoked by intraplantar injection of alpha,beta-methylene ATP
(alpha,beta-meATP). Third, PK2 concentration-dependently potentiated alpha,beta
meATP-activated currents in rat dorsal root ganglion (DRG) neurons. Finally, PK2
receptors and intracellular signal transduction were involved in PK2 potentiation
of alpha,beta-meATP-induced mechanical allodynia and alpha,beta-meATP-activated
currents, since the potentiation were blocked by PK2 receptor antagonist PKRA and
selective PKC inhibitor GF 109203X. These results suggested that PK2 facilitated
mechanical allodynia induced by alpha,beta-meATP through a mechanism involved in
sensitization of cutaneous P2X receptors expressed by nociceptive nerve endings.
PMID- 26435026
TI - Inhibition of development of experimental abdominal aortic aneurysm by c-jun N
terminal protein kinase inhibitor combined with lysyl oxidase gene modified
smooth muscle progenitor cells.
AB - Chronic inflammation, imbalance between the extracellular matrix synthesis and
degradation, and loss of vascular smooth muscle cells (SMCs) contribute to the
development of abdominal aortic aneurysm (AAA). The purpose of this study was to
investigate the effect of the therapy with periaortic incubation of c-Jun N
terminal protein kinase inhibitor SP600125 infused from an osmotic pump and
subadventitial injection of lysyl oxidase (LOX) gene modified autologous smooth
muscle progenitor cells (SPCs) on treatment of AAA in a rabbit model. Obvious
dilation of the abdominal aorta in the control group was caused by periaortic
incubation of calcium chloride and elastase. But the progression of aortic
dilation was significantly decreased after the treatment with SP600125 and LOX
gene modified SPCs compared to the treatment with phosphate-buffered saline. This
therapy could inhibit matrix metalloproteinases expression, enhance elastin
synthesis, improve preservation of elastic laminar integrity, benefit SPCs
survival and restore SMCs population. It seemed that this method might provide a
novel therapeutic strategy to treat AAA.
PMID- 26435027
TI - The role of nitric oxide donors in schizophrenia: Basic studies and clinical
applications.
AB - Schizophrenia is a complex and chronic mental health disease that affects nearly
1% of the population worldwide. While the current antipsychotic medications have
profoundly impacted the treatment of schizophrenia over the past 50 years, the
newer atypical antipsychotics have not fulfilled initial expectations, and
enormous challenges remain in long-term treatment of this debilitating disease.
In particular, improved treatment of the negative symptoms and cognitive
dysfunction in schizophrenia which greatly impact overall morbidity is required.
Nitric oxide (NO) is considered as an intra- and inter-cellular messenger in the
brain. The implication of NO in the pathogenesis of schizophrenia is documented.
Specifically, underproduction of NO is linked to this pathology. This, in turn,
indicates that enhancement of nitrergic activity might be beneficial in this
disease. Therefore, novel molecules aiming to increase NO production such as NO
donors might constitute potential candidates for the treatment of schizophrenia.
Here I intended to critically review advances in research of these emerging
molecules for the treatment of this psychiatric disorder. Present analysis
suggests that NO donors might be a promising class of compounds for the treatment
of schizophrenia. However, the potential neurotoxicity and the narrow therapeutic
window of NO donors would add a note of caution in this context.
PMID- 26435028
TI - Bidirectional effects of dexmedetomidine on human platelet functions in vitro.
AB - Platelets express the imidazoline (I)-receptor, I1 and I2, as well as the alpha2
adrenoceptor. Although dexmedetomidine, a selective alpha2-adrenoceptor agonist
with some affinity for the I-receptor is expected to affect platelet function,
the effects of dexmedetomidine on platelet functions remain unclear. In the
present study, we investigated the effects of dexmedetomidine on human platelet
functions in vitro. The effects of dexmedetomidine on platelet aggregation were
examined using aggregometers. The formation of cyclic adenosine monophosphate
(cAMP) and cyclic guanosine monophosphate (cGMP) in platelets was measured by an
enzyme immunoassay. In addition, P-selectin expression in platelets was estimated
by flow cytometry. We showed that dexmedetomidine enhances platelet aggregation.
But in the presence of yohimbine, an alpha2-antagonist, dexmedetomidine
suppressed platelet aggregation. Efaroxan, an I1-antagonist, and methylene blue,
a soluble guanylate cyclase inhibitor, abolished the suppressive effect of
dexmedetomidine, whereas idazoxan, an I2-antagonist, showed no effect.
Dexmedetomidine suppressed cAMP formation and enhanced P-selectin expression in
platelets, and these effects were inhibited by yohimbine. Dexmedetomidine
increased cGMP formation in platelets in the presence of yohimbine, and this
increase was suppressed by efaroxan. These results demonstrated that
dexmedetomidine has both enhancing and suppressive effects on human platelet
functions through its action on the alpha2-adrenoceptor and on the I1-imidazoline
receptor, respectively.
PMID- 26435029
TI - Dinuclear planar chiral ferrocenyl gold(I) & gold(II) complexes.
AB - Oxidation of Au(I) in the presence of Fe(II) allowed for the synthesis of unique
dinuclear ferrocenyl Au(II) complexes via the first reported enantiopure planar
chiral ferrocenyl Au(I) complex. (Spectro)electrochemical studies show that
oxidation at Fe(II) is favoured, but DFT studies suggest that the energy
differences for oxidation of one or the other metal should be quite small.
PMID- 26435030
TI - Diffuse cutaneous bullous mastocytosis with IgM deposits at dermo-epidermal
junction.
AB - Cutaneous mastocytosis is a disease characterized by the infiltration and
proliferation of mast cells in the skin. In children, the most common form of
presentation is urticaria pigmentosa, while the diffuse cutaneous bullous
mastocytosis is one of the rarest subtypes seen. The aim of this paper is to
present a case of diffuse bullous mastocytosis with detection of IgM deposits at
dermo-epidermal junction using direct immunofluorescence (DIF) microscopy. The
diagnosis of diffuse bullous mastocytosis is a challenge, and DIF microscopy is
necessary in order to exclude an autoimmune bullous disorder. However, IgM
deposits at dermo-epidermal junction can be nonspecific, being found in a variety
of skin disorders. A 6-month-old girl presented with bullous lesions and erosions
on the scalp and the trunk. During hospitalization, further bullous lesions
appeared, along with generalized erythrodermia. Skin biopsy revealed aspects of
urticaria pigmentosa. Taking into account the clinical findings, the case was
enclosed as bullous mastocytosis. Treatment included the avoidance of trigger
factors, and administration of antihistamines along with a short-term course of
systemic steroids. The evolution was favorable, with remission of the existing
lesions and without occurrence of new ones.
PMID- 26435031
TI - Intraguild predation of Geocoris punctipes on Eretmocerus eremicus and its
influence on the control of the whitefly Trialeurodes vaporariorum.
AB - BACKGROUND: Geocoris punctipes (Hemiptera: Lygaeidae) and Eretmocerus eremicus
(Hymenoptera: Aphelinidae) are whitefly natural enemies. Previously, under
laboratory conditions, we showed that G. punctipes engages in intraguild
predation (IGP), the attack of one natural enemy by another, on E. eremicus.
However, it is unknown whether this IGP interaction takes place under more
complex scenarios, such as semi-field conditions. Even more importantly, the
effect of this interaction on the density of the prey population requires
investigation. Therefore, the present study aimed to establish whether this IGP
takes place under semi-field conditions and to determine whether the predation
rate of G. punctipes on the whitefly decreases when IGP takes place. RESULTS:
Molecular analysis showed that, under semi-field conditions, G. punctipes
performed IGP on E. eremicus. However, although IGP did take place, the predation
rate by G. punctipes on the whitefly was nevertheless higher when both natural
enemies were present together than when the predator was present alone.
CONCLUSION: While IGP of G. punctipes on E. eremicus does occur under semi-field
conditions, it does not adversely affect whitefly control. The concomitant use of
these two natural enemies seems a valid option for inundative biological control
programmes of T. vaporariorum in tomato. (c) 2015 Society of Chemical Industry.
PMID- 26435032
TI - Analysis-preserving video microscopy compression via correlation and mathematical
morphology.
AB - The large amount video data produced by multi-channel, high-resolution microscopy
system drives the need for a new high-performance domain-specific video
compression technique. We describe a novel compression method for video
microscopy data. The method is based on Pearson's correlation and mathematical
morphology. The method makes use of the point-spread function (PSF) in the
microscopy video acquisition phase. We compare our method to other lossless
compression methods and to lossy JPEG, JPEG2000, and H.264 compression for
various kinds of video microscopy data including fluorescence video and
brightfield video. We find that for certain data sets, the new method compresses
much better than lossless compression with no impact on analysis results. It
achieved a best compressed size of 0.77% of the original size, 25* smaller than
the best lossless technique (which yields 20% for the same video). The compressed
size scales with the video's scientific data content. Further testing showed that
existing lossy algorithms greatly impacted data analysis at similar compression
sizes.
PMID- 26435033
TI - Impact of insulin initiation on glycaemic variability and glucose profiles in a
primary healthcare Type 2 diabetes cohort: analysis of continuous glucose
monitoring data from the INITIATION study.
AB - AIM: To use continuous glucose monitoring to examine the effects of insulin
initiation with glargine, with or without glulisine, on glycaemic variability and
glycaemia in a cohort of people with Type 2 diabetes receiving maximum oral
hypoglycaemic agents in primary healthcare. METHODS: We conducted a post hoc
analysis of continuous glucose monitoring data from 89 participants at baseline
and at 24 weeks after insulin commencement. Indicators of glycaemic variability
(standard deviation, J-index and mean amplitude of glycaemic excursion) and
glycaemia (HbA1c , mean glucose, area under the glucose-time curve) were
assessed. Multi-level regression analysis was used to identify the predictors of
change. RESULTS: Complete glycaemic variability data were available for 78
participants. Of these participants, 41% were women, their mean (sd) age was 59.2
(10.4) years, the median (interquartile range) diabetes duration was 10.4 (6.5,
13.3) years and the median (interquartile range) baseline HbA1c was 82.5 (71.6,
96.7) mmol/mol [9.7 (8.7, 11.0)%]. At baseline, BMI correlated negatively with
standard deviation (r = -0.30) and mean amplitude of glycaemic excursion (r =
0.26), but not with J-index; HbA1c correlated with J-index (r = 0.61) but not
with mean amplitude of glycaemic excursion and standard deviation. After insulin
initiation the mean (sd) glucose level decreased [from 12.0 (3.0) to 8.5 (1.6)
mmol/l; P < 0.001], as did the median (interquartile range) J-index [from 66.9
(47.7, 95.1) to 36.9 (27.6, 49.8) mmol/l; P < 0.001]. Baseline HbA1c correlated
with a greater J-index reduction (r = -0.45; P < 0.001). The mean amplitude of
glycaemic excursion and standard deviation values were unchanged. The baseline
temporal profile, showing elevated postprandial morning glucose levels, was
unchanged after insulin initiation, despite an overall reduction in glycaemia.
CONCLUSION: Insulin initiation reduced hyperglycaemia but did not alter glycaemic
variability in adults with Type 2 diabetes receiving maximum oral hypoglycaemic
agents. The most significant postprandial excursions were seen in the morning,
which identifies prebreakfast as the most effective target for short-acting
insulin therapy.
PMID- 26435034
TI - Changes in prevalence of, and risk factors for, lameness in random samples of
English sheep flocks: 2004-2013.
AB - The aims of this study were to update the prevalence of lameness in sheep in
England and identify novel risk factors. A total of 1260 sheep farmers responded
to a postal survey. The survey captured detailed information on the period
prevalence of lameness from May 2012-April 2013 and the prevalence and farmer
naming of lesions attributable to interdigital dermatitis (ID), severe footrot
(SFR), contagious ovine digital dermatitis (CODD) and shelly hoof (SH),
management and treatment of lameness, and farm and flock details. The global mean
period prevalence of lameness fell between 2004 and 2013 from 10.6% to 4.9% and
the geometric mean period prevalence of lameness fell from 5.4% (95% CL: 4.7%
6.0%) to 3.5% (95% CI: 3.3%-3.7%). In 2013, more farmers were using vaccination
and antibiotic treatment for ID and SFR and fewer farmers were using foot
trimming as a routine or therapeutic treatment than in 2004. Two over-dispersed
Poisson regression models were developed with the outcome the period prevalence
of lameness, one investigated associations with farmer estimates of prevalence of
the four foot lesions and one investigated associations with management practices
to control and treat lameness and footrot. A prevalence of ID>10%, SFR>2.5% and
CODD>2.5% were associated with a higher prevalence of lameness compared with
those lesions being absent, however, the prevalence of SH was not associated with
a change in risk of lameness. A key novel management risk associated with higher
prevalence of lameness was the rate of feet bleeding/100 ewes trimmed/year. In
addition, vaccination of ewes once per year and selecting breeding replacements
from never-lame ewes were associated with a decreased risk of lameness. Other
factors associated with a lower risk of lameness for the first time in a random
sample of farmers and a full risk model were: recognising lameness in sheep at
locomotion score 1 compared with higher scores, treatment of the first lame sheep
in a group compared with waiting until >5 were lame, treatment of lame sheep
within 3 days, ease of catching lame sheep and quarantine for >21 days. A
previously known factor associated with a lower risk of lameness was footbathing
to prevent ID. We conclude that the prevalence of lameness in sheep in England
has fallen and that this might be in part because of increased uptake of
managements recently reported as beneficial to control lameness. Routine foot
trimming should be avoided.
PMID- 26435035
TI - Should we monitor mycophenolic acid plasma levels in pediatric renal
transplantation?
PMID- 26435037
TI - Resistant Hypertension and Susceptible Outcomes: Exploring the Benefits of
Aggressive Blood Pressure Control.
PMID- 26435036
TI - Caenorhabditis elegans NONO-1: Insights into DBHS protein structure,
architecture, and function.
AB - Members of the Drosophila behavior/human splicing (DBHS) protein family have been
characterized in the vertebrates Homo sapiens and Mus musculus, and the
invertebrates Drosophila melanogaster and Chironomus tentans. Collectively, both
vertebrate and invertebrate DBHS proteins function throughout gene regulation,
largely but not always, within the nucleus. In this study, we report a structural
and bioinformatic analysis of the DBHS protein family to guide future studies
into DBHS protein function. To explore the structural plasticity of the family,
we describe the 2.4 A crystal structure of Caenorhabditis elegans non-POU domain
containing octamer-binding protein 1 (NONO-1). The structure is dimeric, with a
domain arrangement consistent with mammalian DBHS proteins. Comparison with the
DBHS structures available from H. sapiens reveals that there is inherent domain
flexibility within the homologous DBHS region. Mapping amino acid similarity
within the family to the NONO-1 dimer highlights the dimer interface, coiled-coil
oligomerization motif, and putative RNA binding surfaces. Surprisingly, the
interior surface of RNA recognition motif 2 (RRM2) that faces a large internal
void is highly variable, but the external beta2-beta3 loops of RRM2 show
remarkable preservation. Overall, the DBHS region is under strong purifying
selection, whereas the sequences N- and C-terminal to the DBHS region are less
constrained. The findings described in this study provide a molecular basis for
further investigation into the mechanistic function of the DBHS protein family in
biology.
PMID- 26435038
TI - Prospective comparison of early bone marrow evaluation on day 5 versus day 14 of
the "3 + 7" induction regimen for acute myeloid leukemia.
AB - Evaluation of early response during induction therapy for acute myeloid leukemia
(AML) is used for prognostication and re-induction strategy, yet the optimal
evaluation time point is unknown. Clearance of bone marrow (BM) blasts by day 14
of therapy does not ensure remission; thus, some patients requiring re-induction
are neglected. This study aimed to examine the role of earlier BM evaluation
during induction for predicting remission and overall survival. Results of BM
testing on the 5th and 14th day of intensive induction were prospectively
compared in 127 adult patients with AML. Re-induction was given, based on Day 14
results, to 25 patients. Reduction of the BM blast count to <5% as early as by
the fifth day of induction was more specifically associated with the achievement
of remission compared to Day 14 (88.2% vs. 60%, respectively). Rapid responders
have a better 3-year overall survival (OS). Day 5 results are a stronger
predictor of OS by multivariate analysis and better segregate long-term survivors
than the Day 14th BM count (66% vs. 30%, P = 0.0001 and 48% vs. 37%,
respectively, P = 0.04). The Day 5 evaluation of BM carries significant clinical
information. The benefit of prescribing re-induction based on such early
evaluation should be prospectively studied.
PMID- 26435040
TI - Smoking behaviour and knowledge of the health effects of smoking in patients with
inflammatory bowel disease.
AB - BACKGROUND: The detrimental effect of smoking on development and progression of
Crohn's disease (CD) is generally accepted. AIM: To evaluate the awareness of
smoking risks in a Belgian inflammatory bowel disease (IBD) population. METHODS:
In the out-patient clinic of a tertiary referral centre, 625 consecutive patients
with CD, 238 patients with ulcerative colitis (UC) and 289 non-IBD controls,
filled out a simple questionnaire. This questionnaire included data on smoking
behaviour and awareness of smoking-related health effects, including effects on
IBD. RESULTS: At diagnosis, more CD patients were active smokers compared to UC
(40% vs. 17%, P < 0.001). Remarkably, smoking cessation rates after diagnosis
were similar for CD and UC (both 56%, P = 0.997). The great majority recognised a
detrimental influence of smoking on general health (98-99%), lung cancer (95
97%), myocardial infarction (89-92%) and stroke (78-87%). Although CD patients
more frequently acknowledged risks of smoking on their disease, only 37% were
aware of a link with CD development, 30% of increased surgical rates and 27% of
increased post-operative CD recurrence. Active smokers more frequently denied an
increased risk of surgery and higher post-operative CD recurrence. Intriguingly,
within the active smokers with CD, those not willing to quit smoking most often
denied a potential bad influence of smoking. Taking into account disease
duration, previous surgery, education level, working status and nicotine
dependence, we were unable to define specific subgroups of patients requiring
extra education. CONCLUSION: Although patients with Crohn's disease were better
informed on the detrimental effects of smoking, the awareness rate was still low.
PMID- 26435041
TI - Polysaccharides from Acanthopanax senticosus enhances intestinal integrity
through inhibiting TLR4/NF-kappaB signaling pathways in lipopolysaccharide
challenged mice.
AB - To investigate the role of polysaccharide from Acanthopanax senticosus (ASPS) on
lipopolysaccharide (LPS)-induced intestinal injury, mice in three treatments were
administrated orally with or without ASPS (300 mg/kg body weight) for 14 days,
followed by challenge with LPS or saline. At 4 h post-injection, blood and
intestinal samples of six mice / treatment were collected. The results showed
ASPS ameliorated LPS-induced intestinal morphological deterioration, proven by
improved villus height (P < 0.05) and villus height : crypt depth ratio (P <
0.05). ASPS also elevated the mucosal barrier of LPS-challenged mice, supported
by reduced plasma diamine oxidase (DAO) activity (P < 0.05) and L-lactate (P <
0.05), increased mucosal DAO activity (P < 0.05) as well as enhanced intestinal
tight junction proteins expression involving occludin-1 (P < 0.05) and zonula
occludens-1 (P < 0.05). In addition, ASPS decreased LPS-induced secretion of
inflammatory mediators, including tumor necrosis factor (TNF)-alpha (P < 0.05)
and prostaglandin E2 (P < 0.05). Also, ASPS down-regulated messenger RNA
expression of toll-like receptor 4 (TLR4) and its downstream signals, including
myeloid differentiation factor 88 (P < 0.05), TNF-alpha receptor-associated
factor 6 (P < 0.05), as well as nuclear factor (NF)-kappaB p65 (P < 0.05) and its
protein expression. These findings suggest that ASPS improves intestinal
integrity under inflammation conditions connected with inhibiting TLR4/NF-kappaB
signaling pathways.
PMID- 26435039
TI - Retinal vascular imaging in early life: insights into processes and risk of
cardiovascular disease.
AB - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality
globally. In recent years, studies have shown that the origins of CVD may be
traced to vascular and metabolic processes in early life. Retinal vascular
imaging is a new technology that allows detailed non-invasive in vivo assessment
and monitoring of the microvasculature. In this systematic review, we described
the application of retinal vascular imaging in children and adolescents, and we
examined the use of retinal vascular imaging in understanding CVD risk in early
life. We reviewed all publications with quantitative retinal vascular assessment
in two databases: PubMed and Scopus. Early life CVD risk factors were classified
into four groups: birth risk factors, environmental risk factors, systemic risk
factors and conditions linked to future CVD development. Retinal vascular changes
were associated with lower birth weight, shorter gestational age, low-fibre and
high-sugar diet, lesser physical activity, parental hypertension history,
childhood hypertension, childhood overweight/obesity, childhood
depression/anxiety and childhood type 1 diabetes mellitus. In summary, there is
increasing evidence supporting the view that structural changes in the retinal
microvasculature are associated with CVD risk factors in early life. Thus, the
retina is a useful site for pre-clinical assessment of microvascular processes
that may underlie the future development of CVD in adulthood.
PMID- 26435043
TI - Hydrocarbon Release During Fuel Storage and Transfer at Gas Stations:
Environmental and Health Effects.
AB - At gas stations, fuel is stored and transferred between tanker trucks, storage
tanks, and vehicle tanks. During both storage and transfer, a small fraction of
unburned fuel is typically released to the environment unless pollution
prevention technology is used. While the fraction may be small, the cumulative
release can be substantial because of the large quantities of fuel sold. The
cumulative release of unburned fuel is a public health concern because gas
stations are widely distributed in residential areas and because fuel contains
toxic and carcinogenic chemicals. We review the pathways through which gasoline
is chronically released to atmospheric, aqueous, and subsurface environments, and
how these releases may adversely affect human health. Adoption of suitable
pollution prevention technology should not only be based on equipment and
maintenance cost but also on energy- and health care-saving benefits.
PMID- 26435042
TI - The gap between policy and practice: a systematic review of patient-centred care
interventions in chronic heart failure.
AB - Patient-centred care (PCC) is recommended in policy documents for chronic heart
failure (CHF) service provision, yet it lacks an agreed definition. A systematic
review was conducted to identify PCC interventions in CHF and to describe the PCC
domains and outcomes. Medline, Embase, CINAHL, PsycINFO, ASSIA, the Cochrane
database, clinicaltrials.gov, key journals and citations were searched for
original studies on patients with CHF staged II-IV using the New York Heart
Association (NYHA) classification. Included interventions actively supported
patients to play informed, active roles in decision-making about their goals of
care. Search terms included 'patient-centred care', 'quality of life' and 'shared
decision making'. Of 13,944 screened citations, 15 articles regarding 10 studies
were included involving 2540 CHF patients. Three studies were randomised
controlled trials, and seven were non-randomised studies. PCC interventions
focused on collaborative goal setting between patients and healthcare
professionals regarding immediate clinical choices and future care. Core domains
included healthcare professional-patient collaboration, identification of patient
preferences, patient-identified goals and patient motivation. While the strength
of evidence is poor, PCC has been shown to reduce symptom burden, improve health
related quality of life, reduce readmission rates and enhance patient engagement
for patients with CHF. There is a small but growing body of evidence, which
demonstrates the benefits of a PCC approach to care for CHF patients. Research is
needed to identify the key components of effective PCC interventions before being
able to deliver on policy recommendations.
PMID- 26435044
TI - Comprehensive proteomic analysis of the wheat pathogenic fungus Zymoseptoria
tritici.
AB - Zymoseptoria tritici causes Septoria tritici blotch disease of wheat. To obtain a
comprehensive protein dataset of this fungal pathogen, proteomes of Z. tritici
growing in nutrient-limiting and rich media and in vivo at a late stage of wheat
infection were fractionated by 1D gel or strong cation exchange (SCX)
chromatography and analyzed by LC-MS/MS. A total of 5731, 5376 and 3168 Z.
tritici proteins were confidently identified from these conditions, respectively.
Of these in vitro and in planta proteins, 9 and 11% were predicted to contain
signal peptides, respectively. Functional classification analysis revealed the
proteins were involved in the various cellular activities. Comparison of three
distinct protein expression profiles demonstrates the elevated carbohydrate,
lipid and secondary metabolisms, transport, protein processing and energy
production specifically in the host environment, in contrast to the enhancement
of signaling, defense, replication, transcription and cell division in vitro. The
data provide useful targets towards a better understanding of the molecular basis
of Z. tritici growth, development, stress response and pathogenicity.
PMID- 26435045
TI - Delivery mode and pelvic organ prolapse: a retrospective observational study.
AB - OBJECTIVE: To analyse the associations between delivery mode and symptoms and
signs of pelvic organ prolapse (POP) in a cohort of symptomatic women. DESIGN:
Retrospective observational study. POPULATION: A total of 1258 consecutive women
attending a tertiary urogynaecological unit for the investigation of lower
urinary tract or pelvic floor disorders between January 2012 and December 2014.
METHODS: Obstetric history and clinical examination data were obtained from the
unit database. Prolapse quantification on imaging was performed using stored four
dimensional translabial ultrasound volume data sets. Women were grouped into four
groups according to the most traumatic delivery reported. The presence of
symptoms and signs of POP were compared between delivery groups while controlling
for potential confounders. MAIN OUTCOME MEASURES: Prolapse symptoms, visual
analogue score for prolapse bother, International Continence Society Prolapse
Quantification System findings and ultrasound findings of anterior, central and
posterior compartment descent. RESULTS: Nulliparae showed the lowest prevalence
of most measures of POP, followed by women exclusively delivered by caesarean
section. Highest prevalences were consistently found in women delivered at least
once by forceps, although the differences between this group and women delivered
by normal vaginal delivery and/or vacuum extraction were significant in three out
of eight measures only. Compared with women in the caesarean section group, the
adjusted odds ratios for reporting symptoms of prolapse were 2.4 (95% CI 1.30
4.59) and 3.2 (95% CI 1.65-6.12) in the normal vaginal delivery/vacuum extraction
group and forceps group, respectively. CONCLUSIONS: There is a clear link between
vaginal delivery and symptoms and signs of pelvic organ prolapse in
urogynaecological patients. TWEETABLE ABSTRACT: Compared with caesarean section a
history of vaginal delivery more than doubles the risk for POP.
PMID- 26435046
TI - Clinical outcomes with transoral robotic surgery for supraglottic squamous cell
carcinoma: Experience of a French evaluation cooperative subgroup of GETTEC.
AB - BACKGROUND: Transoral, minimally invasive, organ preservation surgeries are
increasingly used to treat laryngopharyngeal carcinomas to avoid the toxicity
associated with combined chemoradiotherapy (CRT) regimens. This study
investigated the efficiency, safety, and functional outcomes of using transoral
robotic surgery (TORS) to perform supraglottic laryngectomy (SGL). METHODS: This
was a multicenter study using a case series with planned data collection from
2009 to 2012 for patients with supraglottic squamous cell carcinomas (SCCs) who
underwent an SGL using TORS. RESULTS: Eighty-four of the 262 patients underwent
TORS for a supraglottic SCC. Within 24 hours of surgery, 24% of the patients
began an oral diet. The median use of a feeding tube was 8 days for 76% of other
patients. Definitive percutaneous gastrostomy feeding was necessary for 9.5% of
the patients. Twenty-four percent of the patients did require a tracheostomy, and
the median use was 8 days. One percent of the patients had a definitive
tracheostomy. Aspiration pneumonia was observed in 23% of the patients during the
postoperative course, and was responsible for the death of 1 patient.
Postoperative bleeding occurred in 18% of the patients. Based on the pathology
results, 51% of the patients received adjuvant radiation therapy. CONCLUSION:
TORS for SGL, in the intermediate stage of SCC, provides a safe procedure with
good functional outcomes and fast recovery times; however, adverse events are
possible. Consequently, this technique requires good selection criteria for the
patients to reduce the risk of postoperative complications. (c) 2015 Wiley
Periodicals, Inc. Head Neck 38: E1097-E1101, 2016.
PMID- 26435047
TI - Effect of obesity on neonatal outcomes in pregnancies with preterm premature
rupture of membranes.
AB - BACKGROUND: Maternal obesity is associated with increased systemic inflammation
and an increased risk of preterm premature rupture of membranes. There is an
established association between an inflammatory intrauterine environment and
adverse neonatal outcomes that is independent of gestational age and mediated by
the fetal inflammatory response. It is unknown whether the maternal systemic
inflammation that is present in obese women influences the intrauterine
environment and predisposes the fetus to adverse neonatal outcomes after preterm
premature rupture of membranes. OBJECTIVE: The purpose of this study was to
determine whether maternal obesity is associated with adverse neonatal outcomes
in pregnancies that are complicated by preterm premature rupture of membranes.
STUDY DESIGN: This was a secondary analysis of the Maternal-Fetal Medicine Units
Network Randomized Clinical Trial on the Beneficial Effects of Antenatal
Magnesium Sulfate. Women with singleton pregnancies that were affected by preterm
premature rupture of membranes who delivered live-born infants between 24 + 0 and
33 + 6 weeks of gestation were included. An adverse neonatal outcome was defined
as a composite outcome of neonatal death, severe necrotizing enterocolitis,
respiratory distress syndrome, sepsis, or severe intraventricular hemorrhage. The
rates of the composite outcome were compared between obese (body mass index, >=30
kg/m(2)) and nonobese women. Multivariable logistic regression was used to
evaluate the independent effect of obesity on neonatal outcomes. Magnesium
sulfate administration, steroid administration, maternal diabetes mellitus,
gestational age at delivery, indomethacin exposure, birthweight, and
chorioamnionitis were all considered as possible covariates in the multivariable
regression models. RESULTS: Three hundred twenty-five of the 1288 women (25.2%)
who were included were obese, and 202 of these women (62.2%) had neonates with
adverse outcomes. In univariable analysis, maternal prepregnancy obesity was
associated with increased odds of an adverse neonatal outcome (odds ratio, 0.30,
95% confidence interval, 1.00-1.68). However, in our multivariable logistic
regression model, gestational age at delivery (odds ratio, 0.93, 95% confidence
interval, 0.92-0.94 per day), but not maternal obesity (odds ratio, 1.02, 95%
confidence interval, 0.75-1.38), was associated with adverse neonatal outcomes.
Obese African American women experienced preterm premature rupture of membranes
(189 vs 196 days; p < .001) and delivery (199 vs 205 days; p < .001) earlier than
nonobese African American women. This difference was not seen in non-African
American women. CONCLUSIONS: Maternal obesity was not associated independently
with adverse neonatal outcomes in pregnancies that were affected by preterm
premature rupture of membranes after adjustment for gestational age at birth.
However, obese African American women rupture and deliver earlier than other
women, which causes increased neonatal morbidity.
PMID- 26435048
TI - Electronic storage capacity of ceria: role of peroxide in Aux supported on
CeO2(111) facet and CO adsorption.
AB - Density functional theory (DFT+U) was used to study the adsorption of Aux (x = 1
4) clusters on the defective CeO2(111) facet and CO adsorption on the
corresponding Aux/CeO2-x catalyst, in this work Aux clusters are adsorbed onto
the CeO2-x + superoxide/peroxide surface. When Au1 is supported on the CeO2(111)
facet with an O vacancy, the strong electronegative Au(delta-) formed is not
favorable for CO adsorption. When peroxide is adsorbed on the CeO2(111) facet
with the O vacancy, Aux was oxidized, resulting in stable Aux adsorption on the
defective ceria surface with peroxide, which promotes CO adsorption on the
Aux/CeO2-x catalyst. With more Au atoms in supported Aux clusters, CO adsorption
on this surface becomes stronger. During both the Au being supported on CeO2-x
and CO being adsorbed on Aux/CeO2-x, CeO2 acts as an electron buffer that can
store/release the electrons. These results provide a scientific understanding for
the development of high-performance rare earth catalytic materials.
PMID- 26435049
TI - Reducing consistency in human realism increases the uncanny valley effect;
increasing category uncertainty does not.
AB - Human replicas may elicit unintended cold, eerie feelings in viewers, an effect
known as the uncanny valley. Masahiro Mori, who proposed the effect in 1970,
attributed it to inconsistencies in the replica's realism with some of its
features perceived as human and others as nonhuman. This study aims to determine
whether reducing realism consistency in visual features increases the uncanny
valley effect. In three rounds of experiments, 548 participants categorized and
rated humans, animals, and objects that varied from computer animated to real.
Two sets of features were manipulated to reduce realism consistency. (For humans,
the sets were eyes-eyelashes-mouth and skin-nose-eyebrows.) Reducing realism
consistency caused humans and animals, but not objects, to appear eerier and
colder. However, the predictions of a competing theory, proposed by Ernst Jentsch
in 1906, were not supported: The most ambiguous representations-those eliciting
the greatest category uncertainty-were neither the eeriest nor the coldest.
PMID- 26435051
TI - Enhancement of Solar Fuel Production Schemes by Using a Ru,Rh,Ru Supramolecular
Photocatalyst Containing Hydroxide Labile Ligands.
AB - Polyazine-bridged Ru(II)Rh(III)Ru(II) complexes with two halide ligands, Cl(-) or
Br(-), bound to the catalytically active Rh center are efficient single-component
photocatalysts for H2O reduction to H2 fuel, with the coordination environment on
Rh impacting photocatalysis. Herein reported is a new, halide-free
Ru(II)Rh(III)Ru(II) photocatalyst with OH(-) ligands bound to Rh, further
enhancing the photocatalytic reactivity of the structural motif. H2 production
experiments using the photocatalyst bearing OH(-) ligands at Rh relative to the
analogues bearing halides at Rh in solvents of varying polarity (DMF, CH3CN, and
H2O) suggest that ion pairing with halides deactivates photocatalyst function,
representing an exciting phenomenon to exploit in the development of catalysts
for solar H2 production schemes.
PMID- 26435050
TI - The effect of auditory verbal imagery on signal detection in hallucination-prone
individuals.
AB - Cognitive models have suggested that auditory hallucinations occur when internal
mental events, such as inner speech or auditory verbal imagery (AVI), are
misattributed to an external source. This has been supported by numerous studies
indicating that individuals who experience hallucinations tend to perform in a
biased manner on tasks that require them to distinguish self-generated from non
self-generated perceptions. However, these tasks have typically been of limited
relevance to inner speech models of hallucinations, because they have not
manipulated the AVI that participants used during the task. Here, a new paradigm
was employed to investigate the interaction between imagery and perception, in
which a healthy, non-clinical sample of participants were instructed to use AVI
whilst completing an auditory signal detection task. It was hypothesized that AVI
usage would cause participants to perform in a biased manner, therefore falsely
detecting more voices in bursts of noise. In Experiment 1, when cued to generate
AVI, highly hallucination-prone participants showed a lower response bias than
when performing a standard signal detection task, being more willing to report
the presence of a voice in the noise. Participants not prone to hallucinations
performed no differently between the two conditions. In Experiment 2,
participants were not specifically instructed to use AVI, but retrospectively
reported how often they engaged in AVI during the task. Highly hallucination
prone participants who retrospectively reported using imagery showed a lower
response bias than did participants with lower proneness who also reported using
AVI. Results are discussed in relation to prominent inner speech models of
hallucinations.
PMID- 26435052
TI - Influence of Y(3+), Gd(3+), and Lu(3+) co-doping on the phase and luminescence
properties of monoclinic Eu:LaVO4 particles.
AB - Nano-sized particles of monoclinic-LaVO4 were prepared in a short reaction time
of 30 minutes by employing a microwave assisted hydrothermal synthesis in the
presence of glycerol, which was used both as a solvent and structure-directing
agent. The tetragonal-LaVO4 is known to show strong luminescence properties when
doped with Ln(3+), whereas the monoclinic-LaVO4 is usually considered not
suitable for luminescence and therefore luminescence properties of monoclinic
LaVO4 doped with Ln(3+) ions are seldom investigated. Due to the scarce amount of
research on the topic of luminescence of Ln(3+) doped monoclinic-LaVO4 in this
paper a detailed study of solid state luminescence properties, including quantum
yields, of nano-sized monoclinic-LaVO4 doped with different molar percentages of
Eu(3+) is presented. It was observed that the 12.5%Eu(3+) doped sample showed the
strongest luminescence properties. Additionally a study of the influence of
different rare-earth ions (Y(3+), Gd(3+), Lu(3+)) co-doped into the particles was
performed in order to explore the potential of increasing the luminescence of
these materials. Furthermore stable colloidal suspensions of the Eu(3+) doped
monoclinic-LaVO4 nanoparticles showing strong red emission could be obtained.
PMID- 26435053
TI - Role of RNA Branchedness in the Competition for Viral Capsid Proteins.
AB - To optimize binding-and packaging-by their capsid proteins (CP), single-stranded
(ss) RNA viral genomes often have local secondary/tertiary structures with high
CP affinity, with these "packaging signals" serving as heterogeneous nucleation
sites for the formation of capsids. Under typical in vitro self-assembly
conditions, however, and in particular for the case of many ssRNA viruses whose
CP have cationic N-termini, the adsorption of CP by RNA is nonspecific because
the CP concentration exceeds the largest dissociation constant for CP-RNA
binding. Consequently, the RNA is saturated by bound protein before lateral
interactions between CP drive the homogeneous nucleation of capsids. But, before
capsids are formed, the binding of protein remains reversible and introduction of
another RNA species-with a different length and/or sequence-is found
experimentally to result in significant redistribution of protein. Here we argue
that, for a given RNA mass, the sequence with the highest affinity for protein is
the one with the most compact secondary structure arising from self
complementarity; similarly, a long RNA steals protein from an equal mass of
shorter ones. In both cases, it is the lateral attractions between bound proteins
that determines the relative CP affinities of the RNA templates, even though the
individual binding sites are identical. We demonstrate this with Monte Carlo
simulations, generalizing the Rosenbluth method for excluded-volume polymers to
include branching of the polymers and their reversible binding by protein.
PMID- 26435054
TI - Impairment of the non-homologous end joining and homologous recombination
pathways of DNA double strand break repair: Impact on spontaneous and radiation
induced mammary and intestinal tumour risk in Apc min/+ mice.
AB - Female Apc(min/+) mice carrying the BALB/c variant of Prkdc or heterozygous
knockout for Xrcc2, were sham- or 2 Gy X-irradiated as adults to compare the
effect of mild impairments of double-strand break (DSB) repair pathways, non
homologous end joining (NHEJ) and homologous recombination (HR) respectively on
spontaneous and radiation-induced mammary and intestinal tumorigenesis. Mice with
impaired NHEJ showed no difference in incidence of spontaneous mammary tumours,
compared with matched controls, (2.46 fold, P=0.121) and significantly less
following irradiation (radiation-induced excess; 0.35 fold, P=0.008). In contrast
mice with impaired HR presented with significantly less spontaneous mammary
tumours than matched controls (0.33 fold, P=0.027) and significantly more
following irradiation (radiation-induced excess; 3.3 fold, P=0.016). Spontaneous
and radiation-induced intestinal adenoma multiplicity in the same groups were
significantly greater than matched controls for mice with impaired NHEJ (sham;
1.29 fold, P<0.001, radiation-induced excess; 2.55 fold, P<0.001) and mice with
impaired HR showed no significant differences (sham; 0.92 fold, P=0.166,
radiation-induced excess; 1.16, P=0.274). Genetic insertion events were common in
spontaneous tumours from NHEJ impaired mice compared with matched controls.
gammaH2AX foci analysis suggests a significantly faster rate of DSB repair
(MANOVA P<0.001) in intestinal than mammary tissue; apoptosis was also higher in
irradiated intestine. To conclude, results suggest that pathway of choice for
repair of spontaneous and radiation-induced DSBs is influenced by tissue type.
NHEJ appears to play a greater role in DSB repair in intestinal tissue since
impairment by functional change of Prkdc significantly increases the rate of mis
repair in intestinal but not mammary tissue. HR appears to play a greater role in
DSB repair in adult mammary tissue since impaired HR results in significant
changes in mammary but not in the intestinal tumorigenesis. This indicates that
early DNA damage response and repair is important for cancer susceptibility and
plays a role in determining tissue specificity of cancer risk.
PMID- 26435055
TI - Concomitant versus sequential therapy for the treatment of Helicobacter pylori
infection: a Greek randomized prospective study.
AB - OBJECTIVE: The objective of this study is to compare, in Greece, a region with
>20% local resistance to clarithromycin, the efficacy rates of the concomitant
versus the sequential H. pylori eradication therapy. MATERIALS AND METHODS: Our
prospective randomized study included 364 patients with newly diagnosed H. pylori
infection, randomized to receive a 10-day concomitant or 10-day sequential
therapy. Treatment outcome was assessed by C(13)-urea breath test at least 4
weeks after therapy. Intention to treat (ITT) and per protocol (PP) analysis of
the eradication rates were performed. Secondary end points included patient
compliance and safety. RESULTS: The concomitant therapy group achieved
statistically significant higher eradication rates when compared with the
sequential treatment group, both in the ITT and in the PP analysis (84.6% versus
70.9%, p = 0.002, and 90.6% versus 78.1%, p = 0.001, respectively), after
adjusting for age, gender, smoking status, and the presence or not of ulcer
and/or non-ulcer dyspepsia. Both groups displayed excellent compliance rates
(99.5% for the concomitant therapy group and 96.2% for the sequential therapy
group, p = 0.067). Regarding treatment safety, major adverse events that led to
the discontinuation of both regimens were few, with no statistical difference
between the two groups (7.0% for the concomitant therapy group and 2.9% for the
sequential therapy group). CONCLUSIONS: Concomitant therapy led to statistically
significant higher eradication rates over sequential therapy. Both therapies
showed excellent compliance and an acceptable safety profile. The 10-day
quadruple concomitant scheme should be the adopted for first-line H. pylori
eradication in Greece.
PMID- 26435057
TI - Surgical management of abnormally invasive placenta: is decreased blood loss due
to participation of gynecologic oncologists?
PMID- 26435056
TI - Analysis of a transgenic Oct4 enhancer reveals high fidelity long-range
chromosomal interactions.
AB - Genome structure or nuclear organization has fascinated researchers investigating
genome function. Recently, much effort has gone into defining relationships
between specific genome structures and gene expression in pluripotent cells. We
previously analyzed chromosomal interactions of the endogenous Oct4 distal
enhancer in pluripotent cells. Here, we derive ES and iPS cells from a transgenic
Oct4 distal enhancer reporter mouse. Using sonication-based Circularized
Chromosome Conformation Capture (4C) coupled with next generation sequencing, we
determined and compared the genome-wide interactome of the endogenous and
transgenic Oct4 distal enhancers. Integrative genomic analysis indicated that the
transgenic enhancer binds to a similar set of loci and shares similar key
enrichment profiles with its endogenous counterpart. Both the endogenous and
transgenic Oct4 enhancer interacting loci were enriched in the open nucleus
compartment, which is associated with active histone marks (H3K4me1, H3K27ac,
H3K4me3 and H3K9ac), active cis-regulatory sequences (DNA hypersensitivity sites
(DHS)), 5-hydroxymethylcytosine (5-hmc), and early DNA replication domains. In
addition, binding of some pluripotency-related transcription factors was
consistently enriched in our 4C sites, and genes in those sites were generally
more highly expressed. Overall, our work reveals critical features that may
function in gene expression regulation in mouse pluripotent cells.
PMID- 26435058
TI - Coexistence of glutamatergic spine synapses and shaft synapses in substantia
nigra dopamine neurons.
AB - Dopamine neurons of the substantia nigra have long been believed to have multiple
aspiny dendrites which receive many glutamatergic synaptic inputs from several
regions of the brain. But, here, using high-resolution two-photon confocal
microscopy in the mouse brain slices, we found a substantial number of common
dendritic spines in the nigral dopamine neurons including thin, mushroom, and
stubby types of spines. However, the number of dendritic spines of the dopamine
neurons was approximately five times lower than that of CA1 pyramidal neurons.
Immunostaining and morphological analysis revealed that glutamatergic shaft
synapses were present two times more than spine synapses. Using local two-photon
glutamate uncaging techniques, we confirmed that shaft synapses and spine
synapses had both AMPA and NMDA receptors, but the AMPA/NMDA current ratios
differed. The evoked postsynaptic potentials of spine synapses showed lower
amplitudes but longer half-widths than those of shaft synapses. Therefore, we
provide the first evidence that the midbrain dopamine neurons have two
morphologically and functionally distinct types of glutamatergic synapses, spine
synapses and shaft synapses, on the same dendrite. This peculiar organization
could be a new basis for unraveling many physiological and pathological functions
of the midbrain dopamine neurons.
PMID- 26435059
TI - Phenotype Prediction of Pathogenic Nonsynonymous Single Nucleotide Polymorphisms
in WFS1.
AB - Wolfram syndrome (WS) is a rare, progressive, neurodegenerative disorder that has
an autosomal recessive pattern of inheritance. The gene for WS, wolfram syndrome
1 gene (WFS1), is located on human chromosome 4p16.1 and encodes a transmembrane
protein. To date, approximately 230 mutations in WFS1 have been confirmed, in
which nonsynonymous single nucleotide polymorphisms (nsSNPs) are the most common
forms of genetic variation. Nonetheless, there is poor knowledge on the
relationship between SNP genotype and phenotype in other nsSNPs of the WFS1 gene.
Here, we analysed 395 nsSNPs associated with the WFS1 gene using different
computational methods and identified 20 nsSNPs to be potentially pathogenic.
Furthermore, to identify the amino acid distributions and significances of
pathogenic nsSNPs in the protein of WFS1, its transmembrane domain was
constructed by the TMHMM server, which suggested that mutations outside of the
TMhelix could have more effects on protein function. The predicted pathogenic
mutations for the nsSNPs of the WFS1 gene provide an excellent guide for
screening pathogenic mutations.
PMID- 26435061
TI - Synthesis of Lipophilic Antioxidants by a Lipase-B-Catalyzed Addition of Peracids
to the Double Bond of 4-Vinyl-2-methoxyphenol.
AB - 4-Vinyl guaiacol (2) was lipophilized through the electrophilic addition of
peracids to its vinylic double bond. Those peracids were formed in situ, by the
Candida antarctica lipase-B-assisted perhydrolysis of carboxylic acids ranging
from C2 to C18, in hydrogen peroxide solution. The addition of peracids with 4-8
carbons in their alkyl chains led to the formation of two regioisomers, with the
prevalence of hydroxyesters bearing a primary free hydroxyl (4c-4e). This
prevalence became more pronounced when peracids with longer alkyl chains (C10
C18) were used. In this case, only isomers 4f-4h were formed. The antioxidant
activity of the resulting hydroxyesters was assessed by means of the conjugated
autoxidizable triene (CAT) assay, and it was found out that the 4-vinyl guaiacol
antioxidant activity was significantly increased by grafting alkyl chains with 2
8 carbons.
PMID- 26435060
TI - Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or
Fructose Consumption In Humans.
AB - Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO)
gene whose physiological role in humans remains incompletely defined. Here we
investigated the impact of dietary interventions that affect systemic glucose and
lipid metabolism on plasma adropin concentrations in humans. Consumption of
glucose or fructose as 25% of daily energy requirements (E) differentially
affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex
or age. Glucose consumption reduced plasma adropin from 3.55 +/- 0.26 to 3.28 +/-
0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 +/-
0.29 to 3.93 +/- 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup
(HFCS) as 25% E had no effect (3.43 +/- 0.32 versus 3.39 +/- 0.24 ng/ml, N = 26).
Overall, the effect of glucose, HFCS and fructose on circulating adropin
concentrations were similar to those observed on postprandial plasma triglyceride
concentrations. Furthermore, increases in plasma adropin levels with fructose
intake were most robust in individuals exhibiting hypertriglyceridemia.
Individuals with low plasma adropin concentrations also exhibited rapid increases
in plasma levels following consumption of breakfasts supplemented with lipids.
These are the first results linking plasma adropin levels with dietary sugar
intake in humans, with the impact of fructose consumption linked to systemic
triglyceride metabolism. In addition, dietary fat intake may also increase
circulating adropin concentrations.
PMID- 26435062
TI - Caregiver burden in atypical dementias: comparing frontotemporal dementia,
Creutzfeldt-Jakob disease, and Alzheimer's disease.
AB - BACKGROUND: Caregiver burden is a significant issue in the treatment of dementia
and a known contributor to institutionalization of patients with dementia.
Published data have documented increased caregiver burden in behavioral variant
frontotemporal dementia (bvFTD) compared to Alzheimer's disease (AD). Another
atypical dementia with high-perceived caregiver burden is sporadic Creutzfeldt
Jakob disease (sCJD), but no formal studies have assessed this perception. The
aim of this study was to compare caregiver burden across atypical dementia
etiologies. METHODS: 76 adults with atypical dementia (young-onset AD [YOAD],
bvFTD, language variant FTD [lvFTD], and sCJD) were administered an abbreviated
version of the Zarit Burden Interview (ZBI), Neuropsychiatric Inventory (NPI-Q),
and other assessment instruments during a five-year time period at Johns Hopkins
Hospital (JHH). A Cox regression model examined differences between disease
categories that impact mean ZBI scores. RESULTS: Mean ZBI scores were
significantly different between dementia etiologies, with bvFTD and sCJD having
the highest caregiver burden (p = 0.026). Mean NPI-Q caregiver distress scores
were highest in bvFTD and sCJD (p = 0.002), with sCJD and bvFTD also having the
highest number of endorsed symptom domains (p = 0.012). On regression analyses,
an interactive variable combining final diagnosis category and NPI-Q total
severity score demonstrated statistically significant differences in mean ZBI
scores for sCJD and bvFTD. CONCLUSIONS: This study demonstrates that bvFTD and
sCJD have increased levels of caregiver burden, NPI-Q caregiver distress, total
severity scores, and number of endorsed symptom domains. These results suggest
that higher caregiver burden in bvFTD and sCJD are disease specific and possibly
related to neuropsychiatric symptoms.
PMID- 26435063
TI - Hypoionic shock treatment enables aminoglycosides antibiotics to eradicate
bacterial persisters.
AB - Bacterial persisters, usually being considered as dormant cells that are tolerant
to antibiotics, are an important source for recurrent infection and emergence of
antibiotic resistant pathogens. Clinical eradication of pathogenic persisters is
highly desired but greatly difficult mainly due to the substantial reduction in
antibiotics uptake as well as the non-active state of the drug targets. Here we
report that bacterial persisters (normal growing cells as well) can be
effectively eradicated by aminoglycoside antibiotics upon hypoionic shock (e.g.
pure water treatment) even for less than one minute. Such hypoionic shock
potentiation effect on aminoglycosides is proton motive force-independent, and is
apparently achieved by promoting the entrance of aminoglycosides, speculatively
through the mechanosensitive ion channels. Our revelations may provide a simple
and powerful strategy to eradicate pathogen persisters.
PMID- 26435064
TI - Alternating Voltage Introduced NiCo Double Hydroxide Layered Nanoflakes for an
Asymmetric Supercapacitor.
AB - An electrochemical alternating voltage approach of producing NiCo double
hydroxide (NiCoDH) layered ultrathin nanoflakes with large specific surface area
(355.8 m(2) g(-1)), remarkable specific capacitance and rate capability is
presented. The obtained NiCoDH as anode for asymmetric supercapacitors shows
excellent energy density of 17.5 Wh kg(-1) at high power density of 10.5 kW kg(
1) and cycling stability (91.2% after 10,000 cycles).
PMID- 26435065
TI - Self-Assembled Pico-Liter Droplet Microarray for Ultrasensitive Nucleic Acid
Quantification.
AB - Nucleic acid detection and quantification technologies have made remarkable
progress in recent years. Among existing platforms, hybridization-based assays
have the advantages of being amplification free, low instrument cost, and high
throughput, but are generally less sensitive compared to sequencing and PCR
assays. To bridge this performance gap, we developed a quantitative physical
model for the hybridization-based assay to guide the experimental design, which
leads to a pico-liter droplet environment with drastically enhanced performance
and detection limit several order above any current microarray platform. The pico
liter droplet hybridization platform is further coupled with the on-chip
enrichment technique to yield ultrahigh sensitivity both in terms of target
concentration and copy number. Our physical model, taking into account of
molecular transport, electrostatic intermolecular interactions, reaction
kinetics, suggests that reducing liquid height and optimizing target
concentration will maximize the hybridization efficiency, and both conditions can
be satisfied in a highly parallel, self-assembled pico-liter droplet microarray
that produces a detection limit as low as 570 copies and 50 aM. The pico-liter
droplet array device is realized with a micropatterned superhydrophobic black
silicon surface that allows enrichment of nucleic acid samples by position
defined evaporation. With on-chip enrichment and oil encapsulated pico-liter
droplet arrays, we have demonstrated a record high sensitivity, wide dynamic
range (6 orders of magnitude), and marked reduction of hybridization time from
>10 h to <5 min in a highly repeatable fashion, benefiting from the physics
driven design and nanofeatures of the device. The design principle and technology
can contribute to biomedical sensing and point-of-care clinical applications such
as pathogen detection and cancer diagnosis and prognosis.
PMID- 26435067
TI - The regulation of the Treg/Th17 balance by mesenchymal stem cells in human
systemic lupus erythematosus.
AB - BACKGROUND AND OBJECTIVE: Umbilical cord (UC)-derived mesenchymal stem cells
(MSCs) have shown immunoregulation of various immune cells. The aim of this study
was to investigate the mechanism of UC MSCs in the regulation of peripheral
regulatory T cells (Treg) and T helper 17 (Th17) cells in patients with systemic
lupus erythematosus (SLE). METHODS: Thirty patients with active SLE, refractory
to conventional therapies, were given UC MSCs infusions. The percentages of
peripheral blood CD4+CD25+Foxp3+ regulatory T cells (Treg) and CD3+CD8-IL17A+
Th17 cells and the mean fluorescence intensities (MFI) of Foxp3 and IL-17 were
measured at 1 week, 1 month, 3 months, 6 months, and 12 months after MSCs
transplantation (MSCT). Serum cytokines, including transforming growth factor
beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6),
and IL-17A were detected using ELISA. Peripheral blood mononuclear cells from
patients were collected and co-cultured with UC MSCs at ratios of 1:1, 10:1, and
50:1, respectively, for 72 h to detect the proportions of Treg and Th17 cells and
the MFIs of Foxp3 and IL-17 were determined by flow cytometry. The cytokines in
the supernatant solution were detected using ELISA. Inhibitors targeting TGF
beta, IL-6, indoleamine 2,3-dioxygenase (IDO), and prostaglandin E2 were added to
the co-culture system, and the percentages of Treg and Th17 cells were observed.
RESULTS: The percentage of peripheral Treg and Foxp3 MFI increased 1 week, 1
month, and 3 months after UC MSCs transplantation, while the Th17 proportion and
MFI of IL-17 decreased 3 months, 6 months, and 12 months after the treatment,
along with an increase in serum TGF-beta at 1 week, 3 months, and 12 months and a
decrease in serum TNF-alpha beginning at 1 week. There were no alterations in
serums IL-6 and IL-17A before or after MSCT. In vitro studies showed that the UC
MSCs dose-dependently up-regulated peripheral Treg proportion in SLE patients,
which was not depended on cell-cell contact. However, the down-regulation of Th17
cells was not dose-dependently and also not depended on cell-cell contact.
Supernatant TGF-beta and IL-6 levels significantly increased, TNF-alpha
significantly decreased, but IL-17A had no change after the co-culture. The
addition of anti-TGF-beta antibody significantly abrogated the up-regulation of
Treg, and the addition of PGE2 inhibitor significantly abrogated the down
regulation of Th17 cells. Both anti-IL-6 antibody and IDO inhibitor had no
effects on Treg and Th17 cells. CONCLUSIONS: UC MSCs up-regulate Treg and down
regulate Th17 cells through the regulation of TGF-beta and PGE2 in lupus
patients.
PMID- 26435066
TI - Guiding dengue vaccine development using knowledge gained from the success of the
yellow fever vaccine.
AB - Flaviviruses comprise approximately 70 closely related RNA viruses. These include
several mosquito-borne pathogens, such as yellow fever virus (YFV), dengue virus
(DENV), and Japanese encephalitis virus (JEV), which can cause significant human
diseases and thus are of great medical importance. Vaccines against both YFV and
JEV have been used successfully in humans for decades; however, the development
of a DENV vaccine has encountered considerable obstacles. Here, we review the
protective immune responses elicited by the vaccine against YFV to provide some
insights into the development of a protective DENV vaccine.
PMID- 26435069
TI - A Rare Cause of Dysphagia: Squamous Papillomatosis of the Esophagus.
PMID- 26435068
TI - Carbon monoxide decreases interleukin-1beta levels in the lung through the
induction of pyrin.
AB - Carbon monoxide (CO) can act as an anti-inflammatory effector in mouse models of
lung injury and disease, through the downregulation of pro-inflammatory cytokines
production, though the underlying mechanisms remain unclear. The nucleotide
binding oligomerization domain-, leucine-rich region-, and pyrin domain
containing-3 (NLRP3) inflammasome is a protein complex that regulates the
maturation and secretion of pro-inflammatory cytokines, including interleukin
1beta (IL-1beta). In this report, we show that the CO-releasing molecule (CORM-2)
can stimulate the expression of pyrin, a negative regulator of the NLRP3
inflammasome. CORM-2 increased the transcription of pyrin in the human leukemic
cell line (THP-1) in the absence and presence of lipopolysaccharide (LPS). In THP
1 cells, CORM-2 treatment dose-dependently reduced the activation of caspase-1
and the secretion of IL-1beta, and increased the levels of IL-10, in response to
LPS and adenosine 5'-triphosphate (ATP), an NLRP3 inflammasome activation model.
Genetic interference of IL-10 by small interfering RNA (siRNA) reduced the
effectiveness of CORM-2 in inhibiting IL-1beta production and in inducing pyrin
expression. Genetic interference of pyrin by siRNA increased IL-1beta production
in response to LPS and ATP, and reversed CORM-2-dependent inhibition of caspase-1
activation. CO inhalation (250 ppm) in vivo increased the expression of pyrin and
IL-10 in lung and spleen, and decreased the levels of IL-1beta induced by LPS.
Consistent with the induction of pyrin and IL-10, and the downregulation of lung
IL-1beta production, CO provided protection in a model of acute lung injury
induced by intranasal LPS administration. These results provide a novel mechanism
underlying the anti-inflammatory effects of CO, involving the IL-10-dependent
upregulation of pyrin expression.
PMID- 26435070
TI - Cancelled and Missed Colonoscopy Appointments Not Easy to Measure.
PMID- 26435071
TI - Reply.
PMID- 26435073
TI - Determination of Hg, Fe, Ni, and Co by Miniaturized Optical Emission Spectrometry
Integrated with Flow Injection Photochemical Vapor Generation and Point
Discharge.
AB - A compact and robust OES technique was developed for the sensitive determination
of Hg, Fe, Ni, and Co by utilizing photochemical vapor generation and point
discharge as the sampling technique and the excitation source, respectively.
Mercury cold vapor and the volatile species of Fe, Ni, and Co were generated when
standard or sample solutions containing formic acid were exposed to a UV
photochemical reactor and subsequently separated from the liquid phase for
transport to the microplasma and detection of their atomic emission. Limits of
detection (LODs) of 0.10, 10, 0.20, and 4.5 MUg L(-1) were obtained for Hg, Fe,
Ni and Co, respectively. Compared to conventional microplasma OES, this method
not only broadens the scope of elements amenable to determination, but also
provides 2- and 7-fold improvement in the LODs for Hg and Ni, respectively.
Method validation was demonstrated by analysis of three Certified Reference
Materials (GBW08607, DORM-3, and DORM-4) with satisfactory results, and by good
spike recoveries (93-111%) from three real water samples.
PMID- 26435072
TI - Aryl Bis-Sulfonamide Inhibitors of IspF from Arabidopsis thaliana and Plasmodium
falciparum.
AB - 2-Methylerythritol 2,4-cyclodiphosphate synthase (IspF) is an essential enzyme
for the biosynthesis of isoprenoid precursors in plants and many human pathogens.
The protein is an attractive target for the development of anti-infectives and
herbicides. Using a photometric assay, a screen of 40 000 compounds on IspF from
Arabidopsis thaliana afforded symmetrical aryl bis-sulfonamides that inhibit IspF
from A. thaliana (AtIspF) and Plasmodium falciparum (PfIspF) with IC50 values in
the micromolar range. The ortho-bis-sulfonamide structural motif is essential for
inhibitory activity. The best derivatives obtained by parallel synthesis showed
IC50 values of 1.4 MUm against PfIspF and 240 nm against AtIspF. Substantial
herbicidal activity was observed at a dose of 2 kg ha(-1) . Molecular modeling
studies served as the basis for an in silico search targeted at the discovery of
novel, non-symmetrical sulfonamide IspF inhibitors. The designed compounds were
found to exhibit inhibitory activities in the double-digit micromolar IC50 range.
PMID- 26435074
TI - Electron tomography image reconstruction using data-driven adaptive compressed
sensing.
AB - Electron tomography (ET) is an increasingly important technique for the study of
the three-dimensional morphologies of nanostructures. ET involves the acquisition
of a set of two-dimensional projection images, followed by the reconstruction
into a volumetric image by solving an inverse problem. However, due to
limitations in the acquisition process, this inverse problem is ill-posed (i.e.,
a unique solution may not exist). Furthermore, reconstruction usually suffers
from missing wedge artifacts (e.g., star, fan, blurring, and elongation
artifacts). Recently, compressed sensing (CS) has been applied to ET and showed
promising results for reducing missing wedge artifacts. This uses image sparsity
as a priori knowledge to improve the accuracy of reconstruction, and can require
fewer projections than other reconstruction techniques. The performance of CS
relies heavily on the degree of sparsity in the selected transform domain and
this depends essentially on the choice of sparsifying transform. We propose a new
image reconstruction algorithm for ET that learns the sparsifying transform
adaptively using a dictionary-based approach. We demonstrate quantitatively using
simulations from complex phantoms that this new approach reconstructs the
morphology with higher fidelity than either analytically based CS reconstruction
algorithms or traditional weighted back projection from the same dataset.
SCANNING 38:251-276, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26435075
TI - The Interplay of Size and Surface Functionality on the Cellular Uptake of Sub-10
nm Gold Nanoparticles.
AB - Correlation of the surface physicochemical properties of nanoparticles with their
interactions with biosystems provides key foundational data for nanomedicine. We
report here the systematic synthesis of 2, 4, and 6 nm core gold nanoparticles
(AuNP) featuring neutral (zwitterionic), anionic, and cationic headgroups. The
cellular internalization of these AuNPs was quantified, providing a parametric
evaluation of charge and size effects. Contrasting behavior was observed with
these systems: with zwitterionic and anionic particles, uptake decreased with
increasing AuNP size, whereas with cationic particles, uptake increased with
increasing particle size. Through mechanistic studies of the uptake process, we
can attribute these opposing trends to a surface-dictated shift in uptake
pathways. Zwitterionic NPs are primarily internalized through passive diffusion,
while the internalization of cationic and anionic NPs is dominated by multiple
endocytic pathways. Our study demonstrates that size and surface charge interact
in an interrelated fashion to modulate nanoparticle uptake into cells, providing
an engineering tool for designing nanomaterials for specific biological
applications.
PMID- 26435076
TI - Identification of six new RHCE variant alleles in individuals of diverse racial
origin.
AB - BACKGROUND: The introduction of molecular methods into routine blood typing is
prompting the identification of new blood group alleles. Discrepancies between
the results of genotyping and serology or chance events uncovered during
genotyping prompted additional investigations, which revealed six new RHCE
variant alleles. STUDY DESIGN AND METHODS: Samples from eight blood donors, two
patients (one prenatal), and a patient's relative, all of diverse racial origin,
were analyzed by standard serology methods, targeted genotyping arrays, DNA
sequencing, and allele-specific polymerase chain reaction. RESULTS: Six new RHCE
alleles were identified, namely, RHCE*cE84A, RHCE*ce202G, RHCE*ce307T,
RHCE*Ce377G, RHCE*ce697G,712G,733G,744C, and RHCE*Ce733G. CONCLUSION: While
implementation of new assays in commercial genotyping platforms to detect the
polymorphisms reported here may not be justified given their apparent rarity,
software interpretative algorithms may benefit from the identification of new
alleles for a more accurate determination of genotypes and prediction of
phenotypes.
PMID- 26435077
TI - Multiple functions of syncytiotrophoblast mitochondria.
AB - The human placenta plays a central role in pregnancy, and the syncytiotrophoblast
cells are the main components of the placenta that support the relationship
between the mother and fetus, in apart through the production of progesterone. In
this review, the metabolic processes performed by syncytiotrophoblast
mitochondria associated with placental steroidogenesis are described. The
metabolism of cholesterol, specifically how this steroid hormone precursor
reaches the mitochondria, and its transformation into progesterone are reviewed.
The role of nucleotides in steroidogenesis, as well as the mechanisms associated
with signal transduction through protein phosphorylation and dephosphorylation of
proteins is discussed. Finally, topics that require further research are
identified, including the need for new techniques to study the
syncytiotrophoblast in situ using non-invasive methods.
PMID- 26435078
TI - The role of bariatric surgery in the management of nonalcoholic fatty liver
disease and metabolic syndrome.
AB - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
liver disease worldwide. NAFLD is strongly associated with obesity and metabolic
syndrome (MetS). Current treatment of NAFLD is based on weight reduction.
Bariatric surgery is the most effective treatment for morbid obesity and its
associated metabolic comorbidities. There is evidence indicating that bariatric
surgery improves histological and biochemical parameters of NAFLD, but currently
is not considered a treatment option for NAFLD. The aim of this work is to review
the evidence for the effects of bariatric surgery on NAFLD and the MetS. We found
that insulin resistance, alterations in glucose metabolism, hypertension, plasma
lipids, transaminases, liver steatosis, steatohepatitis and fibrosis improve
after bariatric surgery. Weight loss and improvement of NAFLD are greater after
RYGB than after other interventions. These findings were obtained from
retrospective or cohort studies. There are no studies designed to evaluate liver
specific mortality, liver transplantation, or quality of life. Patients with
indications for bariatric surgery will benefit from the improvements in the MetS
and NAFLD.
PMID- 26435079
TI - Gesture and speech during shared book reading with preschoolers with specific
language impairment.
AB - This study examined (a) the relationship between gesture and speech produced by
children with specific language impairment (SLI) and typically developing (TD)
children, and their mothers, during shared book-reading, and (b) the potential
effectiveness of gestures accompanying maternal speech on the conversational
responsiveness of children. Fifteen preschoolers with expressive SLI were
compared with fifteen age-matched and fifteen language-matched TD children. Child
and maternal utterances were coded for modality, gesture type, gesture-speech
informational relationship, and communicative function. Relative to TD peers,
children with SLI used more bimodal utterances and gestures adding unique
information to co-occurring speech. Some differences were mirrored in maternal
communication. Sequential analysis revealed that only in the SLI group maternal
reading accompanied by gestures was significantly followed by child's
initiatives, and when maternal non-informative repairs were accompanied by
gestures, they were more likely to elicit adequate answers from children. These
findings support the 'gesture advantage' hypothesis in children with SLI, and
have implications for educational and clinical practice.
PMID- 26435080
TI - Cue conflicts in context: interplay between morphosyntax and discourse context in
Danish preschoolers' semantic role assignment.
AB - When learning their first language, children develop strategies for assigning
semantic roles to sentence structures, depending on morphosyntactic cues such as
case and word order. Traditionally, comprehension experiments have presented
transitive clauses in isolation, and cross-linguistically children have been
found to misinterpret object-first constructions by following a word-order
strategy (Chan, Lieven & Tomasello, 2009; Dittmar, Abbot-Smith, Lieven &
Tomasello, 2008; Hakuta, 1982; McDonald, 1989; Slobin & Bever, 1982). In an act
out study, we replicated this finding with Danish preschoolers. However, object
first clauses may be context-sensitive structures, which are infelicitous in
isolation. In a second act-out study we presented OVS clauses in supportive and
unsupportive discourse contexts and in isolation and found that five- to six-year
olds' OVS comprehension was enhanced in discourse-pragmatically felicitous
contexts. Our results extend previous findings of preschoolers' sensitivity to
discourse-contextual cues in sentence comprehension (Hurewitz, 2001; Song &
Fisher, 2005) to the basic task of assigning agent and patient roles.
PMID- 26435081
TI - Prelinguistic vocalizations distinguish pointing acts.
AB - The current study investigated whether point-accompanying characteristics, like
vocalizations and hand shape, differentiate infants' underlying motives of
prelinguistic pointing. We elicited imperative (requestive) and declarative
(expressive and informative) pointing acts in experimentally controlled
situations, and analyzed accompanying characteristics. Experiment 1 revealed that
prosodic characteristics of point-accompanying vocalizations distinguished
requestive from both expressive and informative pointing acts, with little
differences between the latter two. In addition, requestive points were more
often realized with the whole hand than the index finger, while this was the
opposite for expressive and informative acts. Experiment 2 replicated Experiment
1, revealing distinct prosodic characteristics for requestive pointing also when
the referent was distal and when it had an index-finger shape. Findings reveal
that beyond the social context, point-accompanying vocalizations give clues to
infants' underlying intentions when pointing.
PMID- 26435082
TI - Attention to the mouth and gaze following in infancy predict language development
- CORRIGENDUM.
PMID- 26435083
TI - The role of S100 proteins and their receptor RAGE in pancreatic cancer.
AB - Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with low
survival rates. Current therapeutic treatments have very poor response rates due
to the high inherent chemoresistance of the pancreatic-cancer cells. Recent
studies have suggested that the receptor for advanced glycation end products
(RAGE) and its S100 protein ligands play important roles in the progression of
PDAC. We will discuss the potential role of S100 proteins and their receptor,
RAGE, in the development and progression of pancreatic cancer.
PMID- 26435084
TI - Bcl-xL-mediated antioxidant function abrogates the disruption of mitochondrial
dynamics induced by LRRK2 inhibition.
AB - We have used the human neuroblastoma cell line SH-SY5Y overexpressing Bcl-xL (SH
SY5Y/Bcl-xL) to clarify the effects of this mitochondrial protein on the control
of mitochondrial dynamics and the autophagic processes which occur after the
inhibition of leucine-rich repeat kinase 2 (LRRK2) with GSK2578215A. In wild type
(SH-SY5Y/Neo) cells, GSK2578215A (1nM) caused a disruption of mitochondrial
morphology and an imbalance in intracellular reactive oxygen species (ROS) as
indicated by an increase in dichlorofluorescein fluorescence and 4
hydroxynonenal. However, SH-SY5Y/Bcl-xL cells under GSK2578215A treatment, unlike
the wild type, preserved a high mitochondrial membrane potential and did not
exhibit apoptotical chromatins. In contrast to wild type cells, in SH-SY5Y/Bcl-xL
cells, GSK2578215A did not induce mitochondrial translocation of neither dynamin
related protein-1 nor the proapoptotic protein, Bax. In SH-SY5Y/Neo, but not SH
SY5Y/Bcl-xL cells, mitochondrial fragmentation elicited by GSK2578215A precedes
an autophagic response. Furthermore, the overexpression of Bcl-xL protein
restores the autophagic flux pathway disrupted by this inhibitor. SH-SY5Y/Neo,
but not SH-SY5Y/Bcl-xL cells, responded to LRRK2 inhibition by an increase in the
levels of acetylated tubulin, indicating that this was abrogated by Bcl-xL
overexpression. This hyperacetylation of tubulin took place earlier than any of
the above-mentioned events suggesting that it is involved in the autophagic flux
interruption. Pre-treatment with tempol prevented the GSK2578215A-induced
mitochondrial fragmentation, autophagy and the rise in acetylated tubulin in SH
SY5Y/Neo cells. Thus, these data support the notion that ROS act as a second
messenger connexion between LRRK2 inhibition and these deleterious responses,
which are markedly alleviated by the Bcl-xL-mediated ROS generation blockade.
PMID- 26435085
TI - An efficient and reproducible method for improving growth of a soil alga
(Chlorococcum infusionum) for toxicity assays.
AB - This study evaluated five methods of soil inoculation using the soil alga
Chlorococcum infusionum to determine the most efficient and reproducible method
for promoting the growth of soil algae for toxicity testing. The five techniques
included application of C. infusionum in a circle on top of the soil, to a
central spot on top of the soil, to a central spot in the subsoil, to one side on
top of the soil, and application divided between a circle and a central spot on
top of the soil. Of these, the first method generated the greatest amount of
chlorophyll fluorescence and was the method with the best reproducibility. We
evaluated the applicability of this method in an assessment of the toxicity of
copper and nickel to C. infusionum in two representative standard soils. Copper
(20-75 mg/kg for OECD soil and 20-60 mg/kg Lufa 2.2 soil) and nickel (400-500
mg/kg for OECD soil and 60-100 mg/kg Lufa 2.2 soil) reduced the chlorophyll
fluorescence of C. infusionum when the inoculation was delivered in a circle on
top of both soil types. To our knowledge, this is the first study to assess the
suitability of different soil algal inoculation methods for terrestrial toxicity
testing.
PMID- 26435086
TI - Short-Term Effects of Kinesiotaping on Pain and Joint Alignment in Conservative
Treatment of Hallux Valgus.
AB - OBJECTIVE: The main aim of this study was to measure short-term effects of
kinesiotaping on pain and joint alignment in the conservative treatment of hallux
valgus. METHOD: Twenty-one female patients diagnosed with a total of 34 feet with
hallux valgus (13 bilateral, 6 right, and 2 left) participated in this study.
Kinesiotaping was implemented after the first assessment and renewed in days 3,
7, and 10. The main outcome measures were pain, as assessed using visual analog
scale, and hallux adduction angle, as measured by goniometry. Secondary outcome
measure was patients' functional status, as measured by Foot Function Index and
the hallux valgus scale of the American Orthopaedic Foot and Ankle Society
(AOFAS). The radiographic results were also measured before and after 1 month of
treatment. The Wilcoxon test was used to compare the differences between initial
and final scores of AOFAS, as well as FFI scales and hallux valgus angle
assessment scores. RESULTS: There was a significant reduction in goniometric
measurement of hallux valgus angle (P = .001). There was a significant reduction
in pain intensity (P = .001) and AOFAS and Foot Function Index scores at the end
of the treatment (P = .001 and P = .001, respectively). There was a significant
difference between radiographic results in 1-month control (P = .009).
CONCLUSIONS: For this group of female patients, pain and joint alignment were
improved after a 10-day kinesiotape implementation in patients with hallux
valgus. The findings showed short-term decreased pain and disability in hallux
valgus deformity.
PMID- 26435087
TI - Effect of Interactive Neurostimulation Therapy on Inflammatory Response in
Patients With Chronic and Recurrent Mechanical Neck Pain.
AB - OBJECTIVE: The purpose of this study is to evaluate the effect of treatment with
a novel noninvasive interactive neurostimulation device (InterX5000) on the
production of inflammatory biomarkers in chronic and recurrent mechanical neck
pain (NP) syndrome. METHODS: This study represents pilot biological data from a
randomized controlled clinical trial. Twenty-five NP patients and 14 asymptomatic
subjects included for baseline comparison only completed the study. The patients
received 6 InterX5000 or placebo treatments within 2 weeks, and pretreatment and
post-treatment blood samples were collected for in vitro determination of
biomarker production. Whole blood cell cultures were activated by
lipopolysaccharide or by the combination of lipopolysaccharide and
phytohemagglutinin for 24 to 48 hours. The levels of tumor necrosis factor alpha
(TNFalpha) and its soluble type II receptor (sTNFR II), interleukin (IL) 1, IL-1
receptor antagonist (IL-1RA), IL-6, IL-10, and monocyte chemotactic protein
(CCL2/MCP-1) were determined by specific immunoassays. RESULTS: Compared with
asymptomatic subjects, baseline production levels of all proinflammatory
mediators (TNFalpha, IL-1beta, IL-6, and CCL2/MCP-1) were significantly augmented
or trended higher (P = .000-.008) in patients with NP. Of the anti-inflammatory
markers, only IL-1RA was significantly elevated (P = .004). The increase in IL-10
and tumor necrosis factor receptor II levels did not reach statistical
significance. Neither InterX5000 nor placebo therapy had any significant effect
on the production of the inflammatory mediators over the study period.
CONCLUSION: This investigation determined that inflammatory cytokine pathways are
activated in NP patients but found no evidence that a short course of InterX5000
treatment normalized the production of inflammatory biomarkers.
PMID- 26435095
TI - Limitations of care and do not resuscitate orders: A patient's/relative's
perspective.
PMID- 26435094
TI - Novel in vivo imaging analysis of an inner ear drug delivery system: Drug
availability in inner ear following different dose of systemic drug injections.
AB - Systemic application of drugs is commonly used in clinical situations. Some of
these drugs are ototoxic. Since there are few studies on in vivo monitoring of
drug delivery dynamics, the time course or bioavailability of drugs in the inner
ear of live animals following systemic drug application remains unknown. For
instance, it is unknown whether the volume of a drug delivered systemically
correlates with its inner ear pharmacokinetics. We previously established a new
in vivo imaging system to monitor drug delivery in live mice. In the present
study, we used this system to compare drug concentration in the inner ear over
time after systemic drug injections. We used transgenic GFAP-Luc mice that harbor
a firefly luciferase gene expression cassette regulated by 12 kb of murine GFAP
promoter and human beta-globin intron 2. Luciferin delivered into the inner ear
of these mice reacts with luciferase, and the resulting signals are detected in
GFAP-expressing cells in the cochlear nerve. Thus, we assessed in the inner ear
the intensity and duration of luciferin/luciferase signals after systemic
injections of different volumes of luciferin. An IVIS((r)) imaging system was
used to observe signals, and these signals were compared to the drug dynamics of
luciferin delivered through subcutaneous (sc) injections. The volume of sc
injected drug correlated significantly with photon counts measured in the inner
ear. Photons were detected almost immediately after injection, peaking 20 min
after injection. Drug concentration did not affect inner ear signals. Luciferin
injected systemically appeared in the inner ear between highest and lowest
concentration. Drug volume is an important parameter to know if the inner ear
requires a higher level of the drug. We observed that it is the volume of a drug
not its concentration-that is the important factor. Indeed, the more volume of a
drug injected systemically increased the concentration of that drug in the inner
ear. This study provides a better understanding of in vivo drug delivery dynamics
measured in the inner ear. Further studies will show whether a high dosage of
drug is effective or not.
PMID- 26435096
TI - Determinants of Dyspnea in Chronic Heart Failure.
AB - BACKGROUND: Dyspnea is a hallmark symptom of heart failure (HF), associated with
impaired functional capacity and quality of life. The experience of dyspnea is
multifactorial and may originate from different sources. This study set out to
examine the relative importance of potential contributors to dyspnea, ie, disease
severity, inflammation and psychologic distress in a large prospective cohort of
chronic HF patients. This study further aimed to examine the differential
influence of cognitive and somatic symptoms of psychologic distress. METHODS AND
RESULTS: Dyspnea complaints (Health Complaints Scale), demographic and clinical
variables, and psychologic factors (ie, depression, anxiety, and Type D
personality) were assessed in 464 HF patients (mean age 66.0 y, 70% men) at
baseline and 1-year follow-up. Inflammatory markers (ie, tumor necrosis factor
[TNF] alpha, interleukin [IL] 6, IL-10, soluble TNF receptors 1 and 2) were also
assessed at both time points in a subsample (n = 247). Linear mixed modeling
analysis with maximum likelihood estimation showed that when determinant clusters
were entered separately, comorbid chronic obstructive pulmonary disease (COPD)
was significantly associated with dyspnea complaints (P = .039), as were
depression (P < .001) and anxiety (P < .001), whereas inflammation did not
significantly affect dyspnea complaints. When all determinant clusters and
covariates were entered together, results showed that body mass index (P = .013),
COPD (P = .034), age (P = .005), depression (P < .001), and anxiety (P < .001)
were significant independent associates of dyspnea complaints. Somatic depressive
and somatic anxiety symptoms were responsible for these latter associations.
CONCLUSIONS: The experience and report of dyspnea in HF is determined foremost by
somatic symptoms of psychologic distress, being of older age, being overweight,
and having comorbid COPD, with disease severity and systemic inflammation levels
playing an ancillary role. These findings suggest that psychologic distress
should be considered when treating dyspnea complaints in patients with HF.
PMID- 26435098
TI - Home-based supervised exercise versus hospital-based supervised exercise or
unsupervised walk advice as treatment for intermittent claudication: a systematic
review.
AB - OBJECTIVE: To evaluate the effects of home-based supervised exercise vs hospital
based supervised exercise, and the effects of home-based supervised exercise vs
unsupervised "go home and walk advice" on daily life and corridor-walking
capacity, health-related quality of life and patient-reported functional walking
capacity in patients with intermittent claudication. DATA SOURCES: Systematic
literature searches were conducted in PubMed, EMBASE, ProQuest, the Cumulative
Index to Nursing and Allied Health Literature (CINAHL), the Allied and
Complementary Medicine Database (AMED), the Cochrane Library, and a number of
Health Technology Assessment (HTA)-databases in October 2014. STUDY SELECTION:
Randomized controlled trials and non-randomized controlled trials (> 100
patients) were considered for inclusion. DATA EXTRACTION: Data extraction and
risk of bias assessment was performed independently and discussed in meetings.
DATA SYNTHESIS: Seven randomized controlled trials and 2 non-randomized
controlled studies fulfilled the inclusion criteria. The included studies had
some, or major, limitations. CONCLUSION: Based on a low quality of evidence, home
based supervised exercise may lead to less improvement in maximum and pain-free
walking distance, and in more improvement in daily life walking capacity,
compared with hospital-based supervised exercise. Home-based supervised exercise
may improve maximum and pain-free walking distance compared with "go home and
walk advice" and result in little or no difference in health-related quality of
life and functional walking capacity compared with hospital-based supervised
exercise or "go home and walk advice". Further research is needed to establish
the optimal exercise modality for these patients.
PMID- 26435097
TI - Intersections Between Microbiome and Heart Failure: Revisiting the Gut
Hypothesis.
AB - Microbes play an important role in human health and disease. In the setting of
heart failure (HF), substantial hemodynamic changes, such as hypoperfusion and
congestion in the intestines, can alter gut morphology, permeability, function,
and possibly the growth and composition of gut microbiota. These changes can
disrupt the barrier function of the intestines and exacerbate systemic
inflammation via microbial or endotoxin translocation into systemic circulation.
Furthermore, cardiorenal alterations via metabolites derived from gut microbiota
can potentially mediate or modulate HF pathophysiology. Recently, trimethylamine
N-oxide (TMAO) has emerged as a key mediator that provides a mechanistic link
between gut microbiota and multiple cardiovascular diseases, including HF.
Potential intervention strategies which may target this microbiota-driven
pathology include dietary modification, prebiotics/probiotics, and selective
binders of microbial enzymes or molecules, but further investigations into their
safety and efficacy are warranted.
PMID- 26435099
TI - Development of a patient-reported outcome: the Neck OutcOme Score (NOOS)--Content
and construct validity.
AB - OBJECTIVE: To develop a patient-reported outcome evaluating the impact of neck
pain. The results of item generation and reduction and subscale structure in
support of the content and construct validity of the measure are reported.
METHODS: Items were generated from the literature and through focus groups
including patients with neck pain and healthcare professionals, respectively.
Item reduction was based on focus groups and field-tested questionnaire data.
Construct validity was assessed using exploratory factor analysis. RESULTS: Focus
groups containing 24 patients (mean age 57.2 (standard deviation (SD) 15.9)
years, range 24-85 years); 19 women) and 12 healthcare professionals were
conducted before data saturation was achieved. A total of 196 patients with neck
pain (mean age 47.8 (SD 13.7) years), range 18-89 years; 146 women) completed the
preliminary questionnaire. Overall 35 items were removed from the original 69. A
multidimensional questionnaire, divided into five subscales, was developed from
the remaining 34 items: mobility; symptoms; sleep disturbance; everyday activity
and pain; and participation in everyday life. Exploratory factor analysis
supported a 5-subscale structure. CONCLUSION: The Neck OutcOme Score has
excellent content validity and preliminary results support a 5-subscale
structure. Additional work is needed to assess the reliability, further construct
validity and responsiveness.
PMID- 26435100
TI - Reply by Hueber et al.
PMID- 26435102
TI - Reply by Elshal et al.
PMID- 26435101
TI - Re: Photoselective Vaporization of the Prostate for Benign Prostatic Hyperplasia
Using the 180 Watt System: Multicenter Study of the Impact of Prostate Size on
Safety and Outcomes and Re: GreenLightTM Laser (XPS) Photoselective Vapo
Enucleation versus Holmium Laser Enucleation of the Prostate for the Treatment of
Symptomatic Benign Prostatic Hyperplasia: A Randomized Controlled Study: P. A.
Hueber, M. N. Bienz, R. Valdivieso, H. Lavigueur-Blouin, V. Misrai, M. Rutman, A.
E. Te, B. Chughtai, N. J. Barber, A. M. Emara, R. Munver, Q. D. Trinh and K. C.
Zorn J Urol 2015; 194: 462-469. and A. M. Elshal, M. A. Elkoushy, A. R. El-Nahas,
A. M. Shoma, A. Nabeeh, S. Carrier and M. M. Elhilali J Urol 2015; 193: 927-934.
PMID- 26435103
TI - Derivation and validation of simple anthropometric equations to predict adipose
tissue mass and total fat mass with MRI as the reference method.
AB - The reference organ-level body composition measurement method is MRI. Practical
estimations of total adipose tissue mass (TATM), total adipose tissue fat mass
(TATFM) and total body fat are valuable for epidemiology, but validated
prediction equations based on MRI are not currently available. We aimed to derive
and validate new anthropometric equations to estimate MRI-measured
TATM/TATFM/total body fat and compare them with existing prediction equations
using older methods. The derivation sample included 416 participants (222 women),
aged between 18 and 88 years with BMI between 15.9 and 40.8 (kg/m2). The
validation sample included 204 participants (110 women), aged between 18 and 86
years with BMI between 15.7 and 36.4 (kg/m2). Both samples included mixed
ethnic/racial groups. All the participants underwent whole-body MRI to quantify
TATM (dependent variable) and anthropometry (independent variables). Prediction
equations developed using stepwise multiple regression were further investigated
for agreement and bias before validation in separate data sets. Simplest
equations with optimal R (2) and Bland-Altman plots demonstrated good agreement
without bias in the validation analyses: men: TATM (kg)=0.198 weight (kg)+0.478
waist (cm)-0.147 height (cm)-12.8 (validation: R 2 0.79, CV=20 %, standard error
of the estimate (SEE)=3.8 kg) and women: TATM (kg)=0.789 weight (kg)+0.0786 age
(years)-0.342 height (cm)+24.5 (validation: R (2) 0.84, CV=13 %, SEE=3.0 kg).
Published anthropometric prediction equations, based on MRI and computed
tomographic scans, correlated strongly with MRI-measured TATM: (R (2) 0.70-0.82).
Estimated TATFM correlated well with published prediction equations for total
body fat based on underwater weighing (R (2) 0.70-0.80), with mean bias of 2.5
4.9 kg, correctable with log-transformation in most equations. In conclusion, new
equations, using simple anthropometric measurements, estimated MRI-measured TATM
with correlations and agreements suitable for use in groups and populations
across a wide range of fatness.
PMID- 26435104
TI - Formation of a Neurosensory Organ by Epithelial Cell Slithering.
AB - Epithelial cells are normally stably anchored, maintaining their relative
positions and association with the basement membrane. Developmental
rearrangements occur through cell intercalation, and cells can delaminate during
epithelial-mesenchymal transitions and metastasis. We mapped the formation of
lung neuroepithelial bodies (NEBs), innervated clusters of
neuroendocrine/neurosensory cells within the bronchial epithelium, revealing a
targeted mode of cell migration that we named "slithering," in which cells
transiently lose epithelial character but remain associated with the membrane
while traversing neighboring epithelial cells to reach cluster sites.
Immunostaining, lineage tracing, clonal analysis, and live imaging showed that
NEB progenitors, initially distributed randomly, downregulate adhesion and
polarity proteins, crawling over and between neighboring cells to converge at
diametrically opposed positions at bronchial branchpoints, where they reestablish
epithelial structure and express neuroendocrine genes. There is little
accompanying progenitor proliferation or apoptosis. Activation of the slithering
program may explain why lung cancers arising from neuroendocrine cells are highly
metastatic.
PMID- 26435105
TI - A Molecular Code for Identity in the Vomeronasal System.
AB - In social interactions among mammals, individuals are recognized by olfactory
cues, but identifying the key signals among thousands of compounds remains a
major challenge. To address this need, we developed a new technique, component
activity matching (CAM), to select candidate ligands that "explain" patterns of
bioactivity across diverse complex mixtures. Using mouse urine from eight
different sexes and strains, we identified 23 components to explain firing rates
in seven of eight functional classes of vomeronasal sensory neurons. Focusing on
a class of neurons selective for females, we identified a novel family of
vomeronasal ligands, steroid carboxylic acids. These ligands accounted for much
of the neuronal activity of urine from some female strains, were necessary for
normal levels of male investigatory behavior of female scents, and were
sufficient to trigger mounting behavior. CAM represents the first step toward an
exhaustive characterization of the molecular cues for natural behavior in a
mammalian olfactory system.
PMID- 26435107
TI - Molecular structure of self-healing polyampholyte hydrogels analyzed from tensile
behaviors.
AB - Recently, charge balanced polyampholytes (PA) have been found to form tough and
self-healing hydrogels. This class of physical hydrogels have a very high
equilibrated polymer concentration in water (ca. 40-50 wt%), and are strongly
viscoelastic. They are synthesized by random copolymerization of equal amounts of
oppositely charged monomers at a high concentration, followed by a dialysis
process of the small counter-ions and co-ions in water. The randomly distributed,
opposite charges of the polymer form multiple ionic bonds of intra- and inter
chains with strength distribution. The strong inter-chain bonds, stabilized by
topological entanglement, serve as quasi-permanent crosslinks, imparting the
elasticity, while the weak bonds, both inter- and intra-chains, reversibly break
and re-form to dissipate energy to toughen the materials. In this work, we intend
to clarify the structure of the physical PA hydrogels from the tensile behaviors
of the PA hydrogels. To clarify the structure and its formation mechanism, we
analysed the tensile behaviors of the samples before and after the dialysis. We
separated the quasi-permanent crosslinking of strong inter-chain bonds and the
dynamic crosslinking of weak inter-chain bonds by using a combined model that
consists of the Upper Convected Maxwell model and the Gent strain hardening
model. The model fitting of the tensile behaviors extracts quantitative
structural parameters, including the densities of weak and strong inter-chain
bonds and the theoretical finite extensibility of polymer chains. Based on the
fitting results of the combined model, the structural parameters of partial
chains at a fixed observation time, including the Kuhn number, Kuhn length, and
chain conformation, are determined using the scaling theory. The effects of
monomer concentration at preparation, the effect of dialysis and the initial
strain rate on the dynamic structure of PA gels, are discussed based on these
analyses.
PMID- 26435108
TI - Fighting Breast Cancer: Better Detection and Better Therapy Make for a Strong One
Two Punch in the Fight Against Breast Cancer.
PMID- 26435109
TI - The Surpassing Joys of Leadership.
PMID- 26435106
TI - Mapping Synaptic Input Fields of Neurons with Super-Resolution Imaging.
AB - As a basic functional unit in neural circuits, each neuron integrates input
signals from hundreds to thousands of synapses. Knowledge of the synaptic input
fields of individual neurons, including the identity, strength, and location of
each synapse, is essential for understanding how neurons compute. Here, we
developed a volumetric super-resolution reconstruction platform for large-volume
imaging and automated segmentation of neurons and synapses with molecular
identity information. We used this platform to map inhibitory synaptic input
fields of On-Off direction-selective ganglion cells (On-Off DSGCs), which are
important for computing visual motion direction in the mouse retina. The
reconstructions of On-Off DSGCs showed a GABAergic, receptor subtype-specific
input field for generating direction selective responses without significant
glycinergic inputs for mediating monosynaptic crossover inhibition. These results
demonstrate unique capabilities of this super-resolution platform for
interrogating neural circuitry.
PMID- 26435110
TI - Authors' Reply.
PMID- 26435111
TI - Referring Providers' Knowledge About Studies Ordered for Their Patients.
PMID- 26435112
TI - Re: "Patients Prefer Results From the Ordering Provider and Access to Their
Radiology Reports".
PMID- 26435113
TI - Communication of Radiology Reports to Patients: Does One Size Fit All?
PMID- 26435114
TI - Diagnostic Reference Levels as They Are or as They Should Be: A Reply to Miller,
Vano, and Rehani.
PMID- 26435115
TI - Complexity and the Impact of Chronic Diseases.
PMID- 26435116
TI - CT Pulmonary Angiography: Using Decision Rules in the Emergency Department.
AB - PURPOSE: The aim of this study was to assess the appropriateness of utilization
and diagnostic yields of CT pulmonary angiography (CTPA), comparing two commonly
applied decision rules, the pulmonary embolism (PE) rule-out criteria (PERC) and
the modified Wells criteria (mWells), in the emergency department (ED) setting.
METHODS: Institutional review board approval was obtained for this HIPAA
compliant, prospective-cohort, academic single-center study. Six hundred two
consecutive adult ED patients undergoing CTPA for suspected PE formed the study
population. The outcome was positive or negative for PE by CTPA and at 6-month
follow-up. PERC and mWells scores were calculated. A positive PERC score was
defined as meeting one or more criteria and a positive mWells score as >4. The
percentage of CT pulmonary angiographic examinations that could have been avoided
and the diagnostic yield of CTPA using PERC, mWells, and PERC applied to a
negative mWells score were calculated. RESULTS: The diagnostic yield of CTPA was
10% (61 of 602). By applying PERC, mWells, and PERC to negative mWells score,
17.6% (106 of 602), 45% (273 of 602), and 17.1% (103 of 602) of CT pulmonary
angiographic examinations, respectively, could have been avoided. The diagnostic
yield in PERC-positive patients was higher than in mWells-positive patients (10%
[59 of 602] vs 8% [49 of 602], P < .0001). Among PERC-negative and mWells
negative patients, the diagnostic yields for PE were 1.9% (2 of 106) and 4% (12
of 273), respectively (P = .004). The diagnostic yield of a negative PERC score
applied to a negative mWells score was 1.9% (2 of 103). CONCLUSIONS: The use of
PERC in the ED has the potential to significantly reduce the utilization of CTPA
and misses fewer cases of PE compared with mWells, and it is therefore a more
efficient decision tool.
PMID- 26435117
TI - Opportunistic Osteoporosis Screening: Addition of Quantitative CT Bone Mineral
Density Evaluation to CT Colonography.
AB - PURPOSE: For patients undergoing CT colonography (CTC), the screening presents an
opportunity for concurrent osteoporosis screening, without increasing radiation
exposure or the time involved for the patient, using proximal femur quantitative
CT-CT x-ray absorptiometry (QCT-CTXA). METHODS: This cohort included 129 women
and 112 men (mean age: 60.1 +/- 8.2 years; range: 50-95 years) who underwent CTC
between March 2013 and September 2014. Areal bone mineral density (BMD; g/cm(2)),
and resultant left femoral neck T-score, was prospectively measured on the supine
CT series. QCT results were reported with the CTC. Chart review evaluated whether
the patients were eligible for BMD screening according to guidelines from the US
Preventive Services Task Force and the National Osteoporosis Foundation
guidelines; whether they had undergone prior BMD testing; and whether QCT results
changed patient management. RESULTS: Overall, 68.0% (164 of 241) of patients from
this cohort had not previously undergone BMD screening. According to the National
Osteoporosis Foundation guidelines, 44.0% (106 of 241) of patients were eligible
for screening. T-scores within the osteopenic and osteoporotic range were
detected in 32.3% (78 of 241) and 5.0% (12 of 241) of patients, respectively. Of
these patients with low BMD, 66.7% (60 of 90) either had not previously undergone
screening or were eligible for BMD testing. Reporting of QCT-CTXA T-scores
altered management in 9 patients (3.7%) who had low BMD. CONCLUSIONS: Maximizing
the pre-existing value from imaging studies is crucial in the current era of
health care reform. We demonstrate that colorectal and osteoporosis screening can
be combined at CT examination, adding clinical and likely economic value.
PMID- 26435118
TI - ACR Appropriateness Criteria Crohn Disease.
AB - Crohn disease is a chronic inflammatory disorder involving the gastrointestinal
tract, characterized by episodic flares and times of remission. Underlying
structural damage occurs progressively, with recurrent bouts of inflammation. The
diagnosis and management of this disease process is dependent on several
clinical, laboratory, imaging, endoscopic, and histologic factors. In recent
years, with the maturation of CT enterography, and MR enterography, imaging has
played an increasingly important role in relation to Crohn Disease. In addition
to these specialized examination modalities, ultrasound and routine CT have
potential uses. Fluoroscopy, radiography, and nuclear medicine may be less
beneficial depending on the clinical scenario. The imaging modality best suited
to evaluating this disease may change, depending on the target population,
severity of presentation, and specific clinical situation. This document presents
seven clinical scenarios (variants) in both the adult and pediatric populations
and rates the appropriateness of the available imaging options. They are
summarized in a consolidated table, and the underlying rationale and supporting
literature are presented in the accompanying narrative. The ACR Appropriateness
Criteria are evidence-based guidelines for specific clinical conditions that are
reviewed every three years by a multidisciplinary expert panel. The guideline
development and review include an extensive analysis of current medical
literature from peer-reviewed journals and the application of a well established
consensus methodology (modified Delphi) to rate the appropriateness of imaging
and treatment procedures by the panel. In those instances in which evidence is
lacking or not definitive, expert opinion may be used to recommend imaging or
treatment.
PMID- 26435119
TI - Can We Predict Patient Wait Time?
AB - PURPOSE: The importance of patient wait-time management and predictability can
hardly be overestimated: For most hospitals, it is the patient queues that drive
and define every bit of clinical workflow. The objective of this work was to
study the predictability of patient wait time and identify its most influential
predictors. METHODS: To solve this problem, we developed a comprehensive list of
25 wait-related parameters, suggested in earlier work and observed in our own
experiments. All parameters were chosen as derivable from a typical Hospital
Information System dataset. The parameters were fed into several time-predicting
models, and the best parameter subsets, discovered through exhaustive model
search, were applied to a large sample of actual patient wait data. RESULTS: We
were able to discover the most efficient wait-time prediction factors and models,
such as the line-size models introduced in this work. Moreover, these models
proved to be equally accurate and computationally efficient. Finally, the
selected models were implemented in our patient waiting areas, displaying
predicted wait times on the monitors located at the front desks. The limitations
of these models are also discussed. CONCLUSIONS: Optimal regression models based
on wait-line sizes can provide accurate and efficient predictions for patient
wait time.
PMID- 26435120
TI - Modality Access: Strategies for Optimizing Throughput.
PMID- 26435121
TI - Unnecessary Repeat Radiologic Examinations in the Emergency Department After
Interfacility Transfer.
PMID- 26435122
TI - The Radiology Communication Quiz: Are You an Effective Communicator?
PMID- 26435123
TI - Radiology Resident Education in France from Medical School Through Board
Certification.
PMID- 26435124
TI - Curies, and Grays, and Sieverts, Oh My: A Guide for Discussing Radiation Dose and
Risk of Molecular Breast Imaging.
PMID- 26435125
TI - Radiology and Radiation Oncology Practices Should Provide Lactation Facilities
for All Eligible Employees.
PMID- 26435126
TI - Functionalized ZnO/ZnO2 n-N straddling heterostructure achieved by oxygen plasma
bombardment for highly selective methane sensing.
AB - Metal oxide semiconductors have been extensively used as reducing gas sensors
with major limitations regarding selectivity and operating temperature which is
relatively high for most of the cases making the device unusable in some critical
situations. Higher operating temperature is also associated with the higher power
consumption, which goes against the miniaturization of the device. In order to
resolve these problems, here we introduced a ZnO/ZnO2 straddling 'n-N' isotype
heterostructure as a highly selective and sensitive methane sensor at moderately
low operating temperature. ZnO-Zn(OH)2 precursor films were treated in oxygen
plasma in a pulsed DC magnetron sputtering system. Morphological analyses by
field emission scanning electron microscopy showed flake like growth of the
grains with high surface roughness, whereas X-ray diffraction (XRD) showed
polycrystalline nature of the films. Polycrystalline ZnO2 peaks were observed in
the XRD pattern in addition to the existing ZnO, which indicates modification of
the precursor to oxygen rich heterostructure of ZnO/ZnO2. This was further
supported by the shifting of the O1s peak in the X-ray photoelectron
spectroscopic analysis. Plasma treated ZnO/ZnO2 heterostructured films were found
to show high selectivity towards methane (with respect to H2S and CO) and
sensitivity (~96%) at a comparatively low operating temperature.
PMID- 26435127
TI - A novel AgNP/DNA/TPdye conjugate-based two-photon nanoprobe for GSH imaging in
cell apoptosis of cancer tissue.
AB - In the present study, a novel two-photon nanoprobe has been developed and
successfully applied in glutathione (GSH) imaging in cell apoptosis of cancer
tissue.
PMID- 26435128
TI - Implicit Racial Biases in Preschool Children and Adults From Asia and Africa.
AB - This research used an Implicit Racial Bias Test to investigate implicit racial
biases among 3- to 5-year-olds and adult participants in China (N = 213) and
Cameroon (N = 257). In both cultures, participants displayed high levels of
racial biases that remained stable between 3 and 5 years of age. Unlike adults,
young children's implicit racial biases were unaffected by the social status of
the other-race groups. Also, unlike adults, young children displayed overt
explicit racial biases, and these biases were dissociated from their implicit
biases. The results provide strong evidence for the early emergence of implicit
racial biases and point to the need to reduce them in early childhood.
PMID- 26435129
TI - The 2012/2013 ABRF Proteomic Research Group Study: Assessing Longitudinal
Intralaboratory Variability in Routine Peptide Liquid Chromatography Tandem Mass
Spectrometry Analyses.
AB - Questions concerning longitudinal data quality and reproducibility of proteomic
laboratories spurred the Protein Research Group of the Association of
Biomolecular Resource Facilities (ABRF-PRG) to design a study to systematically
assess the reproducibility of proteomic laboratories over an extended period of
time. Developed as an open study, initially 64 participants were recruited from
the broader mass spectrometry community to analyze provided aliquots of a six
bovine protein tryptic digest mixture every month for a period of nine months.
Data were uploaded to a central repository, and the operators answered an
accompanying survey. Ultimately, 45 laboratories submitted a minimum of eight LC
MSMS raw data files collected in data-dependent acquisition (DDA) mode. No
standard operating procedures were enforced; rather the participants were
encouraged to analyze the samples according to usual practices in the laboratory.
Unlike previous studies, this investigation was not designed to compare
laboratories or instrument configuration, but rather to assess the temporal
intralaboratory reproducibility. The outcome of the study was reassuring with 80%
of the participating laboratories performing analyses at a medium to high level
of reproducibility and quality over the 9-month period. For the groups that had
one or more outlying experiments, the major contributing factor that correlated
to the survey data was the performance of preventative maintenance prior to the
LC-MSMS analyses. Thus, the Protein Research Group of the Association of
Biomolecular Resource Facilities recommends that laboratories closely scrutinize
the quality control data following such events. Additionally, improved quality
control recording is imperative. This longitudinal study provides evidence that
mass spectrometry-based proteomics is reproducible. When quality control measures
are strictly adhered to, such reproducibility is comparable among many disparate
groups. Data from the study are available via ProteomeXchange under the accession
code PXD002114.
PMID- 26435131
TI - Diabetes in Asians.
AB - The prevalence of diabetes is increasing globally, particularly in Asia.
According to the 2013 Diabetes Atlas, an estimated 366 million people are
affected by diabetes worldwide; 36% of those affected live in the Western Pacific
region, with a significant proportion in East Asia. The reasons for this marked
increase in the prevalence of diabetes can be extrapolated from several distinct
features of the Asian region. First, the two most populated countries, China and
India, are located in Asia. Second, Asians have experienced extremely rapid
economic growth, including rapid changes in dietary patterns, during the past
decades. As a result, Asians tend to have more visceral fat within the same body
mass index range compared with Westerners. In addition, increased insulin
resistance relative to reduced insulin secretory function is another important
feature of Asian individuals with diabetes. Young age of disease onset is also a
distinctive characteristic of these patients. Moreover, changing dietary
patterns, such as increased consumption of white rice and processed red meat,
contributes to the deteriorated lifestyle of this region. Recent studies suggest
a distinctive responsiveness to novel anti-diabetic agents in Asia; however,
further research and efforts to reverse the increasing prevalence of diabetes are
needed worldwide.
PMID- 26435132
TI - Exercise and Depression.
PMID- 26435130
TI - Mutation Profile of Well-Differentiated Thyroid Cancer in Asians.
AB - Recent advances in molecular diagnostics have led to significant insights into
the genetic basis of thyroid tumorigenesis. Among the mutations commonly seen in
thyroid cancers, the vast majority are associated with the mitogen-activated
protein kinase pathway. B-Raf proto-oncogene (BRAF) mutations are the most common
mutations observed in papillary thyroid cancers (PTCs), followed by RET/PTC
rearrangements and RAS mutations, while follicular thyroid cancers are more
likely to harbor RAS mutations or PAX8/peroxisome proliferator-activated receptor
gamma (PPARgamma) rearrangements. Beyond these more common mutations, alterations
in the telomerase reverse transcriptase (TERT) promoter have recently been
associated with clinicopathologic features, disease prognosis, and tumorigenesis
in thyroid cancer. While the mutations underlying thyroid tumorigenesis are well
known, the frequency of these mutations is strongly associated with geography,
with clear differences reported between Asian and Western countries. Of
particular interest is the prevalence of BRAF mutations, with Korean patients
exhibiting the highest rate of BRAF-associated thyroid cancers in the world.
Here, we review the prevalence of each of the most common mutations in Asian and
Western countries, and identify the characteristics of well-differentiated
thyroid cancer in Asians.
PMID- 26435133
TI - Helicobacter pylori Stool Antigen Levels and Serological Biomarkers of Gastric
Inflammation are Associated with Cardio-Metabolic Risk Factors in Type 2 Diabetic
Patients.
AB - BACKGROUND: Helicobacter pylori infection and subsequent gastric inflammation
have been proposed as risk factors for the development of insulin resistance and
cardiovascular disease. In this study we assessed the possible association of H.
pylori bacterial load, and serum biomarker of gastric inflammation with
cardiometabolic risk factors in diabetic patients. METHODS: In this cross
sectional study, 84 H. pylori-infected type 2 diabetic patients were assessed for
anthropometrics, biochemical and clinical measurements. Pearson correlation test,
linear, and logarithmic regression curve estimation models were used to assess
the association of H. pylori stool antigen (HpSAg) levels, and pepsinogen I (PGI)
to pepsinogen II (PGII) ratio with fasting serum glucose, insulin, serum lipid
and lipoprotein parameters, malondialdehyde, high-sensitive C-reactive protein
(hs-CRP), systolic and diastolic blood pressure, body weight, waist circumference
and lipid accumulation product (LAP) index. RESULTS: The mean age of participants
was 54+/-10 years, and 44% were men. Mean HpSAg levels and PGI/PGII ratio were
0.24+/-0.23 MUg/mL and 9.9+/-9.0, respectively. Higher HpSAg as well as lower
PGI/PGII was correlated with higher anthropometric measures and LAP. A
significant negative correlation between PGI/PGII ratio and blood pressure (r=
0.21 and r=-0.22, systolic and diastolic, respectively, P<0.05), serum insulin
(r=-0.17, P=0.05), and hs-CRP (r=-0.17, P=0.05) was observed. A significant
linear association between PGI/PGII ratio with serum triglycerides (gamma=-0.24,
P<0.05), serum high density lipoprotein cholesterol (HDL-C; gamma=0.43, P<0.01),
and triglycerides/HDL-C ratio (gamma=-0.28, P<0.05) were observed. CONCLUSION:
Higher H. pylori bacterial load and lower PGI/PGII ratio was associated with
higher levels of cardiometabolic risk factors in H. pylori infected type 2
diabetic patients.
PMID- 26435134
TI - Serum Concentrations of Ghrelin and Leptin according to Thyroid Hormone
Condition, and Their Correlations with Insulin Resistance.
AB - BACKGROUND: Thyroid hormones can influence energy metabolism and insulin
sensitivity via their interaction with adipocytokines and gut hormones. The aims
of this study were to evaluate differences in serum ghrelin and leptin
concentrations according to thyroid hormone levels, and to investigate the
correlation of insulin resistance. METHODS: A total of 154 patients (57
hyperthyroid patients, 61 euthyroid patients, and 36 hypothyroid patients; mean
age, 47.9 years) were enrolled. Serum leptin, ghrelin, and insulin levels were
measured and insulin resistance was calculated using the formula of the
homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: There were
no differences in mean concentrations of ghrelin or leptin among the three
groups. There were no significant differences in insulin levels between the
groups (P=0.06), although hyperthyroid patients had borderline statistically
significantly higher levels of insulin than did euthyroid subjects by post hoc
test (26.4 MUIU/mL vs. 16.1 MUIU/mL, P=0.057). Regarding HOMA-IR index, the mean
levels were highest in the hyperthyroid group among those of the three groups
(hyperthyroid vs. euthyroid vs. hypothyroid, 6.7 vs. 3.8 vs. 4.4, P=0.068).
Plasma levels of ghrelin were significantly negatively correlated with age,
insulin, glucose, body mass index (BMI), and HOMA-IR. Plasma levels of leptin
showed significant positive correlation with BMI and triglyceride. There were no
significant correlations among thyroid hormone, thyrotropin, ghrelin, leptin, or
insulin. CONCLUSION: The present study found that serum ghrelin, leptin, and
insulin levels didn't differ according to thyroid function conditions. Further
studies with larger numbers of patients are required to establish a direct
relationship between plasma ghrelin, leptin, and thyroid hormone.
PMID- 26435135
TI - Sugar-Sweetened Beverage Consumption Is Associated with Metabolic Syndrome in
Iranian Adults: Tehran Lipid and Glucose Study.
AB - BACKGROUND: Metabolic syndrome (MetS), a cluster of multiple metabolic
abnormalities, is one of the major public health challenges worldwide. The
current study was conducted to evaluate the association between sugar-sweetened
beverage (SSB) consumption and MetS and its components in Iranian adults.
METHODS: This cross-sectional study was conducted among 5,852 men and women, aged
19 to 70 years, who participated in the fourth phase (2009 to 2011) of the Tehran
Lipid and Glucose Study. Demographics, anthropometrics, biochemical measurements,
and blood pressure (BP) were assessed and MetS was defined by National
Cholesterol Education Program Adult Treatment Panel III definition. Frequency and
quantity of SSB intakes including carbonated drinks and synthetic fruit juices
were collected using a validated semiquantitative food frequency questionnaire.
RESULTS: Mean age of participants (43%, men) was 40.6+/-12.9 years. Significant
positive associations between SSBs and waist circumference, triglyceride level,
systolic and diastolic BP in the third and fourth quartile of SSBs were observed,
after adjustment for all potential confounding variables. The odds of MetS in the
third and fourth quartiles compared to the first quartile category of SSBs was
1.21 (95% confidence interval [CI], 1.01 to 1.45) and 1.30 (95% CI, 1.06 to
1.58), respectively (P for trend=0.03). The odds of MetS, abdominal obesity, low
high density lipoprotein cholesterol and elevated BP had increasing trends across
increasing of SSB consumption (P for trend <0.05). CONCLUSION: Higher intake of
SSBs was associated with the higher odds of MetS in adults. It is suggested that
reducing consumption of SSBs could be a practical approach to prevent metabolic
abnormalities.
PMID- 26435136
TI - Sumoylation of Hes6 Regulates Protein Degradation and Hes1-Mediated
Transcription.
AB - BACKGROUND: Hes6 is a transcriptional regulator that induces transcriptional
activation by binding to transcription repressor Hes1 and suppressing its
activity. Hes6 is controlled by the ubiquitin-proteosome-mediated degradation
system. Here we investigated the sumoylation of Hes6 and its functional role in
its rhythmic expression. METHODS: Hes6, SUMO, and ubiquitin were transfected into
HeLa cells and the expression pattern was observed by Western blot and
immunoprecipitation. To confirm the effect of sumoylation on the rhythmic
expression of Hes6, we generated mouse Hes6 promoter-driven GFP-Hes6 fusion
constructs and expressed these constructs in NIH 3T3 cells. RESULTS:
Overexpression of SUMO led to sumoylation of Hes6 at both lysine 27 and 30.
Protein stability of Hes6 was decreased by sumoylation. Moreover, expression of a
Hes6 sumoylation-defective mutant, the 2KR (K27/30R) mutant, or co-expression of
SUMO protease SUSP1 with native Hes6, strongly reduced ubiquitination. In
addition, sumoylation was associated with both the rhythmic expression and
transcriptional regulation of Hes6. Wild type Hes6 showed oscillatory expression
with about 2-hour periodicity, whereas the 2KR mutant displayed a longer period.
Furthermore, sumoylation of Hes6 derepressed Hes1-induced transcriptional
repression. CONCLUSION: Hes6 sumoylation plays an important role in the
regulation of its stability and Hes1-mediated transcription. These results
suggest that sumoylation may be crucial for rhythmic expression of Hes6 and
downstream target genes.
PMID- 26435137
TI - Two Cases of Allergy to Insulin in Gestational Diabetes.
AB - Allergic reaction to insulin is uncommon since the introduction of human
recombinant insulin preparations and is more rare in pregnant than non-pregnant
females due to altered immune reaction during pregnancy. Herein, we report two
cases of allergic reaction to insulin in gestational diabetes that were
successfully managed. One case was a 33-year-old female using isophane-neutral
protamine Hagedorn human insulin and insulin lispro. She experienced dyspnea,
cough, urticaria and itching sensation at the sites of insulin injection
immediately after insulin administration. We discontinued insulin therapy and
started oral hypoglycemic agents with metformin and glibenclamide. The other case
was a 32-year-old female using insulin lispro and insulin detemer. She
experienced pruritus and burning sensation and multiple nodules at the sites of
insulin injection. We changed the insulin from insulin lispro to insulin aspart.
Assessments including immunoglobulin E (IgE), IgG, eosinophil, insulin antibody
level and skin biopsy were performed. In the two cases, the symptoms were
resolved after changing the insulin to oral agents or other insulin preparations.
We report two cases of allergic reaction to human insulin in gestational diabetes
due to its rarity.
PMID- 26435138
TI - Letter: Comparison of Serum Adipocytokine Levels according to Metabolic Health
and Obesity Status (Endocrinol Metab 2015;30:185-94, Tae Hoon Lee et al.).
PMID- 26435139
TI - Response: Comparison of Serum Adipocytokine Levels according to Metabolic Health
and Obesity Status (Endocrinol Metab 2015;30:185-94, Tae Hoon Lee et al.).
PMID- 26435140
TI - Potential Risks and Mitigation Strategies Before the Conduct of a Clinical Trial:
An Industry Perspective.
AB - Conduct of clinical trials has undergone substantial changes over the last two
decades. Newer markets, evolving guidelines and documentation and high cost
involved in conducting the trials have led pharmaceutical companies to prepare a
risk mitigation plan. Extensive monitoring of potential risks is an essential
element of clinical trials which helps to ensure quality and integrity of a
clinical investigation. Every clinical trial has pre (before the trial), conduct
and post phase. This article which has been developed as a result of extensive
research at ground level by a reputed pharmaceutical company to identify the
potential stages of risks that could affect the overall quality and safety of a
trial and its outcome during the pre-phase of trial (the stage of the trial where
the study design is being planned before initiation of the clinical trial). It
includes risks associated with basic study concept, protocol design, Confidential
Disclosure Agreement (CDA) and Clinical Trial Authorization (CTA) application
signing, vendors of central drug laboratory, site and investigator selection,
Clinical Research Coordinator (CRC) meet, Informed Consent Form (ICF), Case
Report Form (CRF)/ Status Report Form (SRF) preparation, Ethics Committee (EC)
submission, etc. have been highlighted. The risk based mitigation strategy (to
develop an effective risk monitoring plan before staring a clinical trial) has
also been suggested by authors. A well-tailored and integrated plan, recognition
of potential risks and their mitigation strategy can result in the pre exclusion
or end to end solution of all the risks associated with pre- phase of clinical
trials.
PMID- 26435142
TI - Modulation of ROS production in photodynamic therapy using a pH controlled
photoinduced electron transfer (PET) based sensitiser.
AB - A new sensitiser (4) for use in photodynamic therapy (PDT) has been developed to
enable control of ROS production as a function of pH. This pH dependent PDT
behaviour was tested in HeLa cells and in SCID mice bearing human xenograft
pancreatic cancer (BxPC-3) tumours.
PMID- 26435143
TI - An amphipathic sequence in the cytoplasmic tail of HIV-1 Env alters cell tropism
and modulates viral receptor specificity.
AB - The human immunodeficiency virus type 1 (HIV-1) 92UG046 Env protein, obtained
from a CD4-independent HIV-1 primary isolate (Zerhouni et al., 2004), has the
ability to initiate an infection in HeLa cells expressing CD4 when carrying the
full-length (FL) Env, but uses CD8 molecules for receptor-mediated entry when
carrying a truncated Env (CT84). To determine whether a specific length or
structure in the cytoplasmic tail (CT) is responsible for this alteration of
tropism, we compared a series of Env constructs with different CT truncations and
the presence or absence of an amphipathic alpha- helical sequence. We found that
truncated constructs containing the alpha-helical LLP-2 structure in their CT
domains conferred a switch from CD4 to CD8 tropism. The results support the
conclusion that the structure of the CT domain can play an important role in
determining receptor specificity.
PMID- 26435144
TI - Curcumin inhibits bovine herpesvirus type 1 entry into MDBK cells.
AB - The generation of antiviral drugs from herbs and other natural resources with
traditionally long-confirmed effects is an efficient approach. So far, no herb or
components from herbs that could inhibit bovine herpesvirus type 1 (BoHV-1)
replication have been described. In this study, the antiviral effect of curcumin,
a natural phenolic constituent of the spice turmeric, on BoHV-1 replication was
evaluated in cell culture. We demonstrated that curcumin impairs BoHV-1 viral
particles and affects the virus post-binding entry process. Furthermore, curcumin
upregulated the proportion of the plasma membrane adopting a lipid raft
conformation in MDBK cells, which supported the previous reports that curcumin
can modulate the lipid bilayer. Though the antiviral mechanism of curcumin on
BoHV-1 needs further study, we identified for the first time a component from
herb that could inhibit BoHV-1 replication, in vitro.
PMID- 26435141
TI - Asparagine deamidation reduces DNA-binding affinity of the Drosophila
melanogaster Scr homeodomain.
AB - Spontaneous deamidation of asparagine is a non-enzymatic post-translational
modification of proteins. Residue Asn 321 is the main site of deamidation of the
Drosophila melanogaster Hox transcription factor Sex Combs Reduced (Scr).
Formation of iso-aspartate, the major deamidation product, is detected by HNCACB
triple-resonance NMR spectroscopy. The rate of deamidation is quantified by
fitting the decay of Asn NH2 side-chain signals in a time-series of (15)N-(1)H
HSQC NMR spectra. The deamidated form of Scr binds to specific DNA target
sequences with reduced affinity as determined by an electrophoretic mobility
shift assay.
PMID- 26435145
TI - Structural features of the O-antigen of Rickettsia typhi, the etiological agent
of endemic typhus.
AB - Elucidation of the O-specific polysaccharide chain of lipopolysaccharide (LPS)
from Rickettsia typhi, the etiological agent of endemic typhus, is described.
Structural information was established by a combination of monosaccharide and
methylation analyses of the O-chain, and by mass (MS) and nuclear magnetic
resonance (NMR) spectrometries of oligosaccharides arised through its
hydrofluoric (HF) acid degradation. Based on the combined data from these
experiments, two major polymer populations of the O-specific chain have been
determined with the following structural features: alpha-L-QuiNAc-(1->4)-[alpha-D
Glc-(1->3)-alpha-L-QuiNAc-(1->4)]n-alpha-D-Glc-(1->4)-alpha-D-Glc->, alpha-D-Glc
(1->3)-alpha-L-QuiNAc-(1->4)-[alpha-D-Glc-(1->3)-alpha-L-QuiNAc-(1->4)]n-alpha-D
Glc->. The linear backbone is most probably flanked with short side chains of D
GlcNAc-(1->3)-alpha-L-QuiNAc-(1->3)-D-GlcNAc-> that are attached to it via L
QuiNAc as a branching point. It is suggested that a dimer alpha-L-QuiNAc-(1->3)
alpha-D-GlcNAc may represent a common epitope in the O-antigens of Proteus
vulgaris OX19 and R. typhi responsible for the observed serological cross
reactivity.
PMID- 26435146
TI - Standardization of serum neutralization assay of Japanese encephalitis virus
(Nakayama NIH strain) on BHK-21 (Cl-13) cell line.
AB - Potency testing of Japanese encephalitis (JE) vaccine has been a complex process
since its inception. To overcome difficulties encountered therein, an alternative
assay, serum neutralization test (SNT), using Baby Hamster Kidney 21 cell line,
has been standardized. The antibody response generated against JE vaccine was
quantified and the assay was found to be sensitive and specific enough with
significant accuracy and precision. On analysis of cell count, a cell
concentration of 1.5 x 104 was selected as the optimum, since concentrations
above and below this resulted in problems of confluent monolayer formation and
incomplete monolayer formation. Incubation time has also been standardized for
measuring cytopathic effect (CPE). Out of the four different time points
selected, 90 min was found to be adequate for 50% reduction in the amount of CPE.
The accuracy of SNT assay is explained in terms of fiducial limits at 95% level.
Inter- and intra-assay reproducibility testing was also performed. A comparison
of potency of JE vaccine by plaque reduction neutralization test (PRNT) and SNT
method was conducted and it was found that SNT can be a reliable approach for
estimating the potency of JE vaccine. The results of this study throw a light on
the utility of SNT assay for the potency estimation of JE vaccine in routine
practice.
PMID- 26435147
TI - Antigenic validation of recombinant hemagglutinin-neuraminidase protein of
Newcastle disease virus expressed in Saccharomyces cerevisiae.
AB - The outer membrane glycoprotein, hemagglutinin-neuraminidase (HN) of Newcastle
disease virus (NDV) is important for virus infection and subsequent immune
response by host, and offers target for development of recombinant antigen-based
immunoassays and subunit vaccines. In this study, the expression of HN protein of
NDV is attempted in yeast expression system. Yeast offers eukaryotic environment
for protein processing and posttranslational modifications like glycosylation, in
addition to higher growth rate and easy genetic manipulation. Saccharomyces
cerevisiae was found to be better expression system for HN protein than Pichia
pastoris as determined by codon usage analysis. The complete coding sequence of
HN gene was amplified with the histidine tag, cloned in pESC-URA under GAL10
promotor and transformed in Saccharomyces cerevisiae. The recombinant HN (rHN)
protein was characterized by western blot, showing glycosylation heterogeneity as
observed with other eukaryotic expression systems. The recombinant protein was
purified by affinity column purification. The protein could be further used as
subunit vaccine.
PMID- 26435148
TI - Monoclonal antibody profiling of cell surface proteins associated with the viral
biofilms on HTLV-1 transformed cells.
AB - Human T lymphotropic virus 1 (HTLV-1) is a pathogenic retrovirus that spreads
predominantly via cell-to-cell contact. Two models of cell-to-cell virus
transmission are proposed: virological synapse (VS) and viral biofilms (VB). Both
infectious structures can be involved in transmission and synergistically enhance
HTLV-1 spread between cells. Although transmission of virus via VB has been
reported, the molecular composition of VB remains poorly understood. In this
study we generated new anti-VB monoclonal antibodies (MAbs) and screenedthem
along with a panel of anti-human cluster of differentiation (CD) MAbs to select
antigens associated with VB. Among four MAbs generated against VB, two MAbs were
identified as anti-CD25 (IL-2RA). We found that antigens CD4, CD150, CD25, CD70,
and CD80 were enriched in VB. We also determined that expression of viral protein
Tax, a central molecule in HTLV-1 transmission, upregulates intercellular
adhesion molecule 1 (ICAM-1), CD95, CD25, CD70, and CD80. Whether these antigens
are essential for VB formation and HTLV-1 infection remains unknown and will be
determined in further experiments.
PMID- 26435149
TI - Effect of ORF119 gene deletion on the replication and virulence of orf virus.
AB - Orf is a severe infectious disease of sheep and goats caused by orf virus (ORFV).
To investigate the role of ORF119 gene of ORFV, we constructed ORFV with deleted
ORF119 gene and LacZ as reporter gene (ORFV-Delta119-LacZ) via homologous
recombination. The results showed that wild-type ORF-SHZ1 and ORFV-Delta119-LacZ
deletion viruses replicated in Vero cells to similar titers. Relative
transcriptional levels of virulence genes OVIFNR, GIF, VEGF and VIL-10 of ORFV
Delta119-LacZ deletion virus were slightly but not significantly lower after 24
hr compared with the wtORF-SHZ1 virus. In vivo experiments showed that 2-month
old lambs inoculated with ORFV-Delta119-LacZ deletion virus exhibited a similar
total clinical score compared with those inoculated with wtORF-SHZ1 virus. Based
on these results, we conclude that deletion of the ORF119 gene has no significant
effect on ORFV replication and virulence.
PMID- 26435150
TI - Porcine epidemic diarrhea virus M protein blocks cell cycle progression at S
phase and its subcellular localization in the porcine intestinal epithelial
cells.
AB - Porcine epidemic diarrhea (PED) caused by virulent strains of porcine epidemic
diarrhea virus (PEDV) is a highly contagious enteric disease of swine
characterized by severe enteritis, vomiting, and watery diarrhea. This study
investigates the subcellular localization and function of PEDV M protein through
examination of its effects on cell growth, cell cycle progression, and
interleukin 8 (IL-8) expression. Our results revealed that the PEDV M protein is
localized throughout the cytoplasm. The M protein altered swine intestinal
epithelial cell line (IEC) growth and induced cell cycle arrest at the S-phase
via the cyclin A pathway. The S-phase arrest is associated with a decrease in
level of cyclin A. Furthermore, our results revealed that the M protein of PEDV
does not induce endoplasmic reticulum (ER) stress and does not activate NF-kappaB
which is responsible for IL-8 and Bcl-2 expression. This is the first report to
demonstrate that the PEDV M protein is localized in the whole cell and induces
cell cycle arrest at the S-phase. This study provides novel findings in the
function of M proteins of PEDV.
PMID- 26435151
TI - Analysis of different HCV NS4B domains for the development of global consensus
sequence.
AB - The non-structural 4B (NS4B) protein of hepatitis C virus (HCV) is a hydrophobic
protein implicated recently in the formation of membranous web, a platform for
the formation of replication complex and thus is potential target for antivirals.
The CLC main workbench was used to generate genotype-specific consensus sequence,
global consensus sequence and a representative phylogenetic tree from non
structural 4 B (NS4B) protein sequences of seven different HCV genotypes reported
from all over the world. The C-terminal domain (CTD) of NS4B protein especially
the residues involved in interaction with ER membrane were found to be highly
conserved. Other residues found to be highly conserved across all HCV genotypes
included; 5 aromatic residues of N-terminal domain (NTD) (F49, W50, W55, F57, and
Y63), 3 hydrophobic leucine residues (L237, L240, L245), and 2 positively charged
residues of CTD (R248 and H250), dimerization motif of transmembrane domain 3
(TMD3) (G143YGAG147) and its surrounding residues (F118 and F155) and TMD1
Ser/Thr cluster residues (T87, S88 and T95) involved in the hydrogen (H) bond
interactions. In short, amino acids of NTD, TMD and CTD domains involved in the
membrane association/anchoring of NS4B and formation of membranous web are highly
conserved and can serve as potential targets for antivirals and peptide vaccines.
These conserved residues formed the basis for the development of five short
peptides proposed to serve as potential therapeutic target. The phylogenetic
analysis was particularly interesting for NS4B sequences of 3a Pakistani
isolates. The high degree of variability prevented the clustering of Pakistani
isolates with other sequences in phylogenetic tree, revealing geographical
disparity.
PMID- 26435152
TI - Molecular characterization and fluorescence analysis of HCV non-structural
proteins NS3, NS3-4A and NS4A of genotype 3a.
AB - Hepatitis C virus (HCV) chronically infects almost 2% of world's population.
Chronic infection can lead to liver failure and hepatocellular carcinoma (HCC).
Approximately 10% of the Pakistani population is infected with HCV and type 3 is
the most prevalent genotype with 75-90% prevalence. In this study we have
developed transiently expressing cell culture based system for the expression of
HCV non-structural NS3, NS3-4A and NS4A proteins of genotype 3a. HCV non
structural genes NS3, NS3-4A and NS4A were cloned in to pFLAG-CMV2 and pEGFP
C1vectors. All vectors were transfected separately to Huh-7 cells and their
protein expression was analyzed by Western blot and immunofluorescence. All
proteins were expressed correctly and in the transfection we have obtained 42-70%
efficiency for all clones. This system can be used for the development of novel
antiviral strategies to inhibit the viral replication, to study apoptosis
pathways induced by HCV, for the evaluation of vaccine candidates and also to
study the role of HCV different signaling pathways.
PMID- 26435153
TI - Preparation and identification of an antiserum against recombinant UL31 protein
of pseudorabies virus.
AB - Pseudorabies virus (PRV) early protein UL31 is a homologue of herpes simplex
virus 1 (HSV-1) UL31, which is a multifunctional protein important for HSV-1
infection. However, the precise roles of PRV UL31 in virus life cycle are still
poorly understood. A relatively crucial tool for uncovering the function of UL31
is an antiserum that specifically detects UL31 in the PRV-infected cells. For
this purpose, a recombinant UL31 protein consisting of N-terminal 27 aa of UL31
fused to EYFP and His-tag was expressed, purified and used for the preparation of
antiserum in BALB/c mice. Our results show that Western blot analysis and
immunofluorescence assay showed that this antiserum could specifically detect the
purified recombinant UL31 as well as full-length UL31 in the PRV infected cells.
These results demonstrate that the prepared antiserum could serve as a valuable
tool for further studies of UL31 functions in PRV infection.
PMID- 26435154
TI - Porcine encephalomyocarditis virus strain BD2 isolated from northern China is
highly virulent for BALB/c mice.
AB - Encephalomyocarditis virus (EMCV) can cause acute myocarditis in young pigs or
reproductive failure in sows. The BD2 strain was isolated from the suspected
piglets with EMCV in China. In order to establish an experimental animal model of
EMCV, eight-weeks-old male BALB/c mice were intraperitonealy inoculated with 0.1
ml of 4*10(5) TCID50 suspension of the EMCV. Infected mice demonstrated hind limb
paralysis, and movement disorder. The mortality rate of the infected group was
100% during the one-week observation period. The viral load in the brain of
challenged mice gradually increased, with a peak level being 6.53 log CCID50/0.1
ml 5 days post infection. The pathological injury in infected mice was presented
as neuronal necrosis. Brown positive staining could be detected in the cytoplasm
of cerebral neurons. These results indicate that the porcine EMCV isolated from
China could replicate in brain tissues and induce acute encephalitis in BALB/c
mice.
PMID- 26435155
TI - Spectrum of VP1 region genetic variants in the foot-and-mouth disease virus
serotype O populations derived from infected cattle tongue epithelium.
AB - RNA virus population exists as a complex distribution of non-identical but
closely related sequences known as viral quasispecies. Variant strains are
selected from this quasispecies population in response to changing environment.
The quasispecies dynamics of a virus existing within an infected host differs
from that in a cell culture-adapted population. This study was carried out to
explore the genetic variations present in the VP1 coding region of the foot-and
mouth disease (FMD) virus serotype O derived directly from infected cattle tongue
epithelium. Molecular clonal populations of two serotype O strains belonging to
lineages Ind2001 (IND 30/2011) and PanAsia2 (IND 5/2011) were sequenced at VP1
coding region. For IND 30/2011, 19 clones were sequenced and analysis showed
variations at 12 nucleotide positions (nt) resulting in 8 amino acid (aa)
replacements. Similarly, for IND 5/2011 virus, 18 clones were sequenced, of which
six showed nt variations leading to 3 aa replacements. Most of the variable
positions mapped to the surface-exposed loops and some of them were found in the
neutralizing antigenic sites (position 81, 149, 169, 186 and 202 of IND 30/2011
and 141 of IND 5/2011), which potentially could be beneficial in rapid adaptive
evolution of the virus by giving rise to antigenic variants to overcome
neutralizing antibodies. These findings encourage further research into the
landscape of the viral quasispecies population in vivo and its implication for
viral ecology.
PMID- 26435156
TI - The association of HBV infection with DNA methyltransferases expression in
hepatocellular carcinoma.
PMID- 26435157
TI - Pyoderma gangrenosum along superficial vein thrombosis during pregnancy.
PMID- 26435158
TI - The controversial existence of the human superior fronto-occipital fasciculus:
Connectome-based tractographic study with microdissection validation.
AB - The superior fronto-occipital fasciculus (SFOF), a long association bundle that
connects frontal and occipital lobes, is well-documented in monkeys but is
controversial in human brain. Its assumed role is in visual processing and
spatial awareness. To date, anatomical and neuroimaging studies on human and
animal brains are not in agreement about the existence, course, and terminations
of SFOF. To clarify the existence of the SFOF in human brains, we applied
deterministic fiber tractography to a template of 488 healthy subjects and to 80
individual subjects from the Human Connectome Project (HCP) and validated the
results with white matter microdissection of post-mortem human brains. The
imaging results showed that previous reconstructions of the SFOF were generated
by two false continuations, namely between superior thalamic peduncle (STP) and
stria terminalis (ST), and ST and posterior thalamic peduncle. The anatomical
microdissection confirmed this finding. No other fiber tracts in the previously
described location of the SFOF were identified. Hence, our data suggest that the
SFOF does not exist in the human brain.
PMID- 26435159
TI - Adrenal cavernous hemangioma associated with myelolipomatous metaplasia.
PMID- 26435160
TI - Response to Donovan et al. Does exposure to hyperglycaemia in utero increase the
risk of obesity and diabetes in the offspring? A critical reappraisal.
PMID- 26435161
TI - Unleashing Optics and Optoacoustics for Developmental Biology.
AB - The past decade marked an optical revolution in biology: an unprecedented number
of optical techniques were developed and adopted for biological exploration,
demonstrating increasing interest in optical imaging and in vivo interrogations.
Optical methods have become faster and have reached nanoscale resolution, and are
now complemented by optoacoustic (photoacoustic) methods capable of imaging whole
specimens in vivo. Never before were so many optical imaging barriers broken in
such a short time-frame: with new approaches to optical microscopy and mesoscopy
came an increased ability to image biology at unprecedented speed, resolution,
and depth. This review covers the most relevant techniques for imaging in
developmental biology, and offers an outlook on the next steps for these
technologies and their applications.
PMID- 26435162
TI - Porous Molybdenum-Based Hybrid Catalysts for Highly Efficient Hydrogen Evolution.
AB - We have synthesized a porous Mo-based composite obtained from a polyoxometalate
based metal-organic framework and graphene oxide (POMOFs/GO) using a simple one
pot method. The MoO2 @PC-RGO hybrid material derived from the POMOFs/GO composite
is prepared at a relatively low carbonization temperature, which presents a
superior activity for the hydrogen-evolution reaction (HER) in acidic media owing
to the synergistic effects among highly dispersive MoO2 particles, phosphorus
doped porous carbon, and RGO substrates. MoO2 @PC-RGO exhibits a very positive
onset potential close to that of 20 % Pt/C, low Tafel slope of 41 mV dec(-1) ,
high exchange current density of 4.8*10(-4) A cm(-2) , and remarkable long-term
cycle stability. It is one of the best high-performance catalysts among the
reported nonprecious metal catalysts for HER to date.
PMID- 26435163
TI - Use of carbonate extraction in analyzing moderately hydrophobic transmembrane
proteins in the mitochondrial inner membrane.
AB - Resistance to sodium carbonate extraction is regarded as a canonical way to
distinguish integral membrane proteins (MPs) from other membrane-associated
proteins. However, it has been observed that carbonate extraction releases some
mitochondrial integral MPs. Here, by analyzing both artificially designed and
native mitochondrial inner MPs containing transmembrane domains (TMDs) of
different hydrophobicities, we show that carbonate treatment can release
moderately hydrophobic TMDs from the mitochondrial inner membrane. These results
suggest that resistance and sensitivity to carbonate extraction may be
interpreted with caution when analyzing the nature of mitochondrial inner MPs.
PMID- 26435164
TI - Gap junction coupling confers isopotentiality on astrocyte syncytium.
AB - Astrocytes are extensively coupled through gap junctions into a syncytium.
However, the basic role of this major brain network remains largely unknown.
Using electrophysiological and computational modeling methods, we demonstrate
that the membrane potential (VM) of an individual astrocyte in a hippocampal
syncytium, but not in a single, freshly isolated cell preparation, can be well
maintained at quasi-physiological levels when recorded with reduced or K(+) free
pipette solutions that alter the K(+) equilibrium potential to non-physiological
voltages. We show that an astrocyte's associated syncytium provides powerful
electrical coupling, together with ionic coupling at a lesser extent, that
equalizes the astrocyte's VM to levels comparable to its neighbors. Functionally,
this minimizes VM depolarization attributable to elevated levels of local
extracellular K(+) and thereby maintains a sustained driving force for highly
efficient K(+) uptake. Thus, gap junction coupling functions to achieve
isopotentiality in astrocytic networks, whereby a constant extracellular
environment can be powerfully maintained for crucial functions of neural
circuits.
PMID- 26435165
TI - Prognostic Value of Ambulatory Blood Pressure in the Obese: The Ambulatory Blood
Pressure-International Study.
AB - The purpose of this study was to compare the predictive value of ambulatory blood
pressure (BP) vs office BP for cardiovascular events during a 5.8-year follow-up
period in the obese and nonobese participants of the Ambulatory Blood Pressure
International Study (n=10,817). Both ambulatory BP and office BP considered
separately were predictive of cardiovascular events. However, in Cox models
including both pressures, only ambulatory BP was associated with outcome. Among
obese patients, the hazard ratios for a 10-mm Hg increase in 24-hour and office
systolic BPs were 1.37 (95% confidence interval, 1.20-1.53) and 0.91 (95%
confidence interval, 0.76-1.07), respectively. Among nonobese patients, the
corresponding hazard ratios were 1.39 (95% confidence interval, 1.31-1.47) and
0.94 (95% confidence interval, 0.88-1.00) (P=not significant vs obese). Similar
results were obtained for diastolic BP and for daytime and nighttime BPs.
Ambulatory BP has similar predictive capacity in obese and nonobese patients,
suggesting that ambulatory BP monitoring is a useful diagnostic tool for the
assessment of obese individuals.
PMID- 26435166
TI - The proportional recovery rule for stroke revisited.
PMID- 26435168
TI - Prevalence of migraine in persons with the 3243A>G mutation in mitochondrial DNA.
AB - BACKGROUND AND PURPOSE: Over the last three decades mitochondrial dysfunction has
been postulated to be a potential mechanism in migraine pathogenesis. The
lifetime prevalence of migraine in persons carrying the 3243A>G mutation in
mitochondrial DNA was investigated. METHODS: In this cross-sectional study, 57
mDNA 3243A>G mutation carriers between May 2012 and October 2014 were included.
As a control group, a population-based cohort from our epidemiological studies on
migraine in Danes was used. History of headache and migraine was obtained by
telephone interview, based on a validated semi-structured questionnaire,
performed by trained physicians. RESULTS: The prevalence of migraine is
significantly higher in persons carrying the 3243A>G mutation than in controls
(58% vs. 18%; P < 0.001). This applies for both subforms of migraine, migraine
without aura (47% vs. 12%; P < 0.001) and migraine with aura (18% vs. 6%; P <
0.001), and in females (58% vs. 24%; P < 0.001) and males (58% vs. 12%; P <
0.001) for any migraine. CONCLUSIONS: A high prevalence of migraine in persons
with the mDNA 3243A>G mutation was found. This finding suggests a clinical
association between a monogenetically inherited disorder of mitochondrial
dysfunction and susceptibility to migraine. Mitochondrial DNA aberrations may
contribute to the pathogenesis of migraine.
PMID- 26435169
TI - Network-based proteomic analysis for postmenopausal osteoporosis in Caucasian
females.
AB - Menopause is one of the crucial physiological events during the life of a woman.
Transition of menopause status is accompanied by increased risks of various
health problems such as osteoporosis. Peripheral blood monocytes can
differentiate into osteoclasts and produce cytokines important for osteoclast
activity. With quantitative proteomics LC-nano-ESI-MS(E) (where MS(E) is elevated
energy MS), we performed protein expression profiling of peripheral blood
monocytes in 42 postmenopausal women with discordant bone mineral density (BMD)
levels. Traditional comparative analysis showed proteins encoded by four genes
(LOC654188, PPIA, TAGLN2, YWHAB) and three genes (LMNB1, ANXA2P2, ANXA2) were
significantly down- and upregulated, respectively, in extremely low- versus high
BMD subjects. To study functionally orchestrating groups of detected proteins in
the form of networks, we performed weighted gene coexpression network analysis
and gene set enrichment analysis. Weighted gene coexpression network analysis
showed that the module including the annexin gene family was most significantly
correlated with low BMD, and the lipid-binding related GO terms were enriched in
this identified module. Gene set enrichment analysis revealed that two
significantly enriched gene sets may be involved in postmenopausal BMD variation
by regulating pro-inflammatory cytokines activities. To gain more insights into
the proteomics data generated, we performed integrative analyses of the datasets
available to us at the genome (DNA level), transcriptome (RNA level), and
proteome levels jointly.
PMID- 26435170
TI - Platelet Adhesion and Thrombus Formation in Whole Blood at Arterial Shear Rate at
the End of Pregnancy.
AB - PROBLEM: Platelet reactivity has not been evaluated in integrated functional
testing during normal pregnancy. Here, we analysed platelet functions under
arterial shear rate in comparison with static conditions. METHOD OF STUDY: Thirty
pregnant women with uncomplicated pregnancies and 30 healthy non-pregnant women
were enrolled in this study. Platelet adhesion to collagen and fibrinogen and
subsequent thrombus formation were measured at arterial shear rate in whole blood
using a microfluidic and imaging system. Standard light transmission
aggregometry, flow cytometry of activation markers in washed platelets and
impedance aggregometry in whole blood were also used to assess platelet
responsiveness in static conditions. RESULTS: Compared to non-pregnant controls,
thrombus formation on collagen fibres and firm platelet adhesion on fibrinogen
under arterial shear rate were significantly reduced in pregnant women. Platelet
aggregometry assays in suspension showed a slight increase in platelet reactivity
in pregnant women. CONCLUSION: While platelet aggregometry and platelet
activation markers in static conditions show little changes in platelet
reactivity, monitoring of platelet adhesion and thrombus growth on collagen or
fibrinogen under flow condition in whole blood indicates a significant decrease
in pregnant women compared to controls. This decrease might contribute to
counteract a hypercoagulable state and to reduce the risk of arterial thrombosis.
PMID- 26435171
TI - Antibiotic prophylaxis for women undergoing caesarean section and infant health.
PMID- 26435167
TI - Diabetes and ageing-induced vascular inflammation.
AB - Diabetes and the ageing process independently increase the risk for
cardiovascular disease (CVD). Since incidence of diabetes increases as people get
older, the diabetic older adults represent the largest population of diabetic
subjects. This group of patients would potentially be threatened by the
development of CVD related to both ageing and diabetes. The relationship between
CVD, ageing and diabetes is explained by the negative impact of these conditions
on vascular function. Functional and clinical evidence supports the role of
vascular inflammation induced by the ageing process and by diabetes in vascular
impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature
include pro-inflammatory cytokines, vascular hyperactivation of nuclear factor
kB, increased expression of cyclooxygenase and inducible nitric oxide synthase,
imbalanced expression of pro/anti-inflammatory microRNAs, and dysfunctional
stress-response systems (sirtuins, Nrf2). In contrast, there are scarce data
regarding the interaction of these mechanisms when ageing and diabetes co-exist
and its impact on vascular function. Older diabetic animals and humans display
higher vascular impairment and CVD risk than those either aged or diabetic,
suggesting that chronic low-grade inflammation in ageing creates a vascular
environment favouring the mechanisms of vascular damage driven by diabetes.
Further research is needed to determine the specific inflammatory mechanisms
responsible for exacerbated vascular impairment in older diabetic subjects in
order to design effective therapeutic interventions to minimize the impact of
vascular inflammation. This would help to prevent or delay CVD and the specific
clinical manifestations (cognitive decline, frailty and disability) promoted by
diabetes-induced vascular impairment in the elderly.
PMID- 26435172
TI - Characterizing nerve growth factor-p75(NTR) interactions and small molecule
inhibition using surface plasmon resonance spectroscopy.
AB - Nerve growth factor (NGF) is critical for the proliferation, differentiation, and
survival of neurons through its binding to the p75(NTR) and TrkA receptors.
Dysregulation of NGF has been implicated in several pathologies, including
neurodegeneration (i.e., Parkinson's and Alzheimer's diseases) and both
inflammatory and neuropathic pain states. Therefore, small molecule inhibitors
that block NGF-receptor interactions have significant therapeutic potential.
Small molecule antagonists ALE-0540, PD90780, Ro 08-2750, and PQC 083 have all
been reported to inhibit NGF from binding the TrkA receptor. Interestingly, the
characterization of the ability of these molecules to block NGF-p75(NTR)
interactions has not been performed. In addition, the inhibitory action of these
molecules has never been evaluated using surface plasmon resonance (SPR)
spectroscopy, which has been proven to be highly useful in drug discovery
applications. In the current study, we used SPR biosensors to characterize the
binding of NGF to the p75(NTR) receptor in addition to characterizing the
inhibitory potential of the known NGF antagonists. The results of this study
provide the first evaluation of the ability of these compounds to block NGF
binding to p75(NTR) receptor. In addition, only PD90780 was effective at
inhibiting the interaction of NGF with p75(NTR), suggesting receptor selectivity
between known NGF inhibitors.
PMID- 26435173
TI - Si78 double cage structure and special optical properties.
AB - We performed first-principles calculations to study the structural stability of
Si78 clusters with or without hydrogen passivation. The calculations reveal that
an endohedral double cage isomer is more stable than the diamond-like structure,
whereas the opposite is found for the hydrogen passivated isomers. In particular,
the hydrogenated double cage and diamond-like structure may display blue shifts
to the visible and UV regions, respectively. The IR vibration spectra, ionization
potential (IP) and electronic density-of-states of the clusters were calculated
and discussed.
PMID- 26435174
TI - Influence of BMP-2 on early follicular development and mRNA expression of oocyte
specific genes in bovine preantral follicles cultured in vitro.
AB - This study evaluates the effect of different concentrations (0, 10, 50 and
100ng/mL) of bone morphogenetic protein-2 (BMP-2) on primordial and secondary
follicle development. It also investigates the effects of FSH and BMP-2 on the
growth, morphology, ultrastructure and expression of mRNA for GDF9, NLRP5 and
NPM2 genes in secondary follicles cultured for 18 days. The presence of BMP-2 at
all tested concentrations increased the development of primordial follicles in
vitro, but the highest concentration of BMP-2 (100 ng/mL) reduced the percentage
of normal follicles when compared with tissues cultured with 10 ng/mL BMP-2.
During culture of secondary follicles, in contrast to higher concentrations (50
or 100 ng/mL), 10 ng/mL BMP-2 kept the morphology of follicles during initial
stages of in vitro culture. This concentration of BMP-2 also benefits maintenance
of the ultrastructure of 18-day cultured follicles. The presence of both BMP-2
and FSH in culture medium resulted in a significant (P<0.05) increase in
follicular diameter after 18 days of culture. However, both FSH and BMP-2 reduced
follicular mRNA expression of GDF9 and NLRP5 when compared to follicles cultured
in media containing only FSH. In combination with FSH, BMP-2 reduced the mRNA
levels of NPM2, when compared to follicles cultured in control medium. It is
concluded from these data that 10 ng/mL BMP-2 promotes the growth of primordial
in vitro and it helps to maintain the ultrastructure of secondary follicles,
while FSH is more important for better expression of follicular markers like GDF9
and NLRP5.
PMID- 26435175
TI - Graphic Somatography: Life Writing, Comics, and the Ethics of Care.
AB - This essay considers the ways in which graphic caregiving memoirs complicate the
idealizing tendencies of ethics of care philosophy. The medium's "capacious"
layering of words, images, temporalities, and perspectives produces "productive
tensions. . . The words and images entwine, but never synthesize" (Chute 2010,
5). In graphic memoirs about care, this "capaciousness" allows for quick
oscillation between the rewards and struggles of care work, representing
ambiguous, even ambivalent attitudes toward care. Graphic memoirs effectively
represent multiple perspectives without synthesis, part of a structural and
thematic ambivalence that provides a provocative counterpart to the abstract
idealism of ethics of care philosophy.
PMID- 26435180
TI - Transition-Metal-Free N-Arylation of Pyrazoles with Diaryliodonium Salts.
AB - A new synthetic method was developed for the N-arylation of pyrazoles using
diaryliodonium salts. The transformation does not require any transition-metal
catalyst and provides the desired N-arylpyrazoles rapidly under mild reaction
condition in the presence of aqueous ammonia solution as a mild base without the
use of inert atmosphere. The chemoselectivity of unsymmetric diaryliodonium salts
was also explored with large number of examples.
PMID- 26435179
TI - Children with Autism Spectrum Disorder scan own-race faces differently from other
race faces.
AB - It has been well documented that people recognize and scan other-race faces
differently from faces of their own race. The current study examined whether this
cross-racial difference in face processing found in the typical population also
exists in individuals with Autism Spectrum Disorder (ASD). Participants included
5- to 10-year-old children with ASD (n=29), typically developing (TD) children
matched on chronological age (n=29), and TD children matched on nonverbal IQ
(n=29). Children completed a face recognition task in which they were asked to
memorize and recognize both own- and other-race faces while their eye movements
were tracked. We found no recognition advantage for own-race faces relative to
other-race faces in any of the three groups. However, eye-tracking results
indicated that, similar to TD children, children with ASD exhibited a cross
racial face-scanning pattern: they looked at the eyes of other-race faces longer
than at those of own-race faces, whereas they looked at the mouth of own-race
faces longer than at that of other-race faces. The findings suggest that although
children with ASD have difficulty with processing some aspects of faces, their
ability to process face race information is relatively spared.
PMID- 26435181
TI - Slow magnetic relaxation of light lanthanide-based linear LnZn2 trinuclear
complexes.
AB - Four isostructural LnZn2 trinuclear complexes, [Ln(NO3){Zn(L)(SCN)}2] (H2L is a
Schiff base ligand derived from o-vanillin and ethylenediamine), were
synthesized, which include light lanthanide ions as spin carriers (Ln = Ce 1, Pr
2, Nd 3, and Sm 4). These complexes involve a linear Zn(ii)-Ln(iii)-Zn(ii) array,
which leads to an axially stressed ligand field and can also cause single
moleluce magnet (SMM) behavior in oblate-type electronic distributions of ground
sublevels found in Ce(iii), Pr(iii), and Nd(iii). Slow magnetic relaxation
behavior was observed in 1 and 3 under an applied bias dc field of 1000 Oe,
whereas such a slow relaxation was not observed in 2 and 4. The appearance of
field-induced SMM behavior in 1 and 3 was correlated with the even-numbered Jz
sublevels of Ce(iii) and Nd(iii) ions known as the Kramers system.
PMID- 26435182
TI - Generic finite element models of orthodontic mini-implants: Are they reliable?
AB - Many finite element (FE) studies used different settings for modeling orthodontic
mini-implants (OMIs). This study aims to compare different approaches for
modeling OMI with FE method, to exhibit the role of key factors in modeling
process. A computerized tomography (CT) dataset of a living human is used to
develop subject-specific FE model of bone specimen, and a microCT was used to
generate the geometry of OMI. Another five models were developed to assess the
effect of changing different settings of FE modeling process. These five models
differed from the subject-specific model in either: (i) bone properties'
assignment method, (ii) geometries and constrains' conditions, or (iii)
simulation method of bone-implant contact (BIC). The models presented significant
differences in maximum principal strain distribution. These differences were most
apparent when the models differed either in the nature of BIC or the method of
assigning bone properties. The models different only in bone geometries showed
differences in the intensity of strain rather than its distribution pattern.
There is a need for assessment and validation of all FE modeling approaches
currently used for simulation of mechanical environment in the bone surrounding
OMIs.
PMID- 26435183
TI - Performance of local optimization in single-plane fluoroscopic analysis for total
knee arthroplasty.
AB - Fluoroscopy-derived joint kinematics plays an important role in the evaluation of
knee prostheses. Fluoroscopic analysis requires estimation of the 3D prosthesis
pose from its 2D silhouette in the fluoroscopic image, by optimizing a
dissimilarity measure. Currently, extensive user-interaction is needed, which
makes analysis labor-intensive and operator-dependent. The aim of this study was
to review five optimization methods for 3D pose estimation and to assess their
performance in finding the correct solution. Two derivative-free optimizers
(DHSAnn and IIPM) and three gradient-based optimizers (LevMar, DoNLP2 and IpOpt)
were evaluated. For the latter three optimizers two different implementations
were evaluated: one with a numerically approximated gradient and one with an
analytically derived gradient for computational efficiency. On phantom data, all
methods were able to find the 3D pose within 1mm and 1 degrees in more than 85%
of cases. IpOpt had the highest success-rate: 97%. On clinical data, the success
rates were higher than 85% for the in-plane positions, but not for the rotations.
IpOpt was the most expensive method and the application of an analytically
derived gradients accelerated the gradient-based methods by a factor 3-4 without
any differences in success rate. In conclusion, 85% of the frames can be analyzed
automatically in clinical data and only 15% of the frames require manual
supervision. The optimal success-rate on phantom data (97% with IpOpt) on phantom
data indicates that even less supervision may become feasible.
PMID- 26435184
TI - Patterning Poly(dimethylsiloxane) Microspheres via Combination of Oxygen Plasma
Exposure and Solvent Treatment.
AB - Here a simple low-cost yet robust route has been developed to prepare
poly(dimethylsiloxane) (PDMS) microspheres with various surface wrinkle patterns.
First, the aqueous-phase-synthesized PDMS microspheres are exposed to oxygen
plasma (OP), yielding the oxidized SiOx layer and the corresponding stiff
shell/compliant core system. The subsequent solvent swelling and solvent
evaporation induce the spontaneous formation of a series of curvature and
overstress-sensitive spherical wrinkles such as dimples, short rodlike
depressions, and herringbone and labyrinth patterns. The effects of the
experimental parameters, including the radius and Young's modulus of the
microspheres, the OP exposure duration, and the nature of the solvents, on these
tunable spherical wrinkles have been systematically studied. The experimental
results reveal that a power-law dependence of the wrinkling wavelength on the
microsphere radius exists. Furthermore, the induced wrinkling patterns are
inherently characteristic of a memory effect and good reversibility. Meanwhile,
the corresponding phase diagram of the wrinkle morphologies on the spherical
surfaces vs the normalized radius of curvature and the excess swelling degree has
been demonstrated. It is envisioned that the introduced strategy in principle
could be applied to other curved surfaces for expeditious generation of well
defined wrinkle morphologies, which not only enables the fabrication of solids
with multifunctional surface properties, but also provides important implications
for the morphogenesis in soft materials and tissues.
PMID- 26435185
TI - One-step separation of nine structural analogues from Poria cocos (Schw.) Wolf.
via tandem high-speed counter-current chromatography.
AB - A novel one-step separation strategy-tandem high-speed counter-current
chromatography (HSCCC) was developed with a six-port valve serving as the switch
interface. Nine structural analogues including three isomers were successfully
isolated from Poria cocos (Schw.) Wolf. by one step. Compared with conventional
HSCCC, peak resolution of target compounds was effectively improved in tandem
one. Purities of isolated compounds were all over 90% as determined by HPLC.
Their structures were then identified via UV, MS and (1)H NMR, and eventually
assigned as poricoic acid B (1), poricoic acid A (2), 3beta,16alpha
dihydroxylanosta-7, 9(11), 24-trien-21-oic acid (3), dehydrotumulosic acid (4),
polyporenic acid C (5), 3-epi-dehydrotumulosic acid (6), 3-o-acetyl-16alpha
hydroxydehydrotrametenolic acid (7), dehydropachymic acid (8) and
dehydrotrametenolic acid (9) respectively. The results indicated that tandem
HSCCC can effectively improve peak resolution of target compounds, and can be a
good candidate for HSCCC separation of structural analogues.
PMID- 26435186
TI - Simultaneous qualitation and quantitation of natural trans-1,4-polyisoprene from
Eucommia ulmoides Oliver by gel permeation chromatography (GPC).
AB - Natural trans-1,4-polyisoprene (TPI) as a functional biomaterial has aroused
great interest for rubber industrial product use. Here, we proposed a method that
enables simultaneous analysis of the content and molecular-weight distribution
(MWD) of natural TPI by gel permeation chromatography (GPC). The natural TPIs
were collected from leaves, fruit coatings and bark of Eucommia ulmoides Oliver
(E. ulmoides) through toluene extraction followed by ethanol purification. The
results of TPI contents from leaves and fruit coatings were shown ca. 3.5% and
13.8%, respectively. Accordingly, limits of detection (LODs) of TPI were
0.58mg/mL from leaves and 0.47mg/mL from fruit coatings. The MWDs of TPI
demonstrated a bimodal distribution from leaves, a unimodal distribution from
bark, and a unimodal distribution with a tiny peak shoulder from fruit coatings.
In real-life E. ulmoides analysis, the results from three independent methods
(GPC, gravimetric method, and infrared spectroscopy) were obtained with good
consistency.
PMID- 26435187
TI - Corrigendum: A Novel Role of Numb as A Regulator of Pro-inflammatory Cytokine
Production in Macrophages in Response to Toll-like Receptor 4.
PMID- 26435188
TI - Understanding Cooperative Behavior Based on the Coevolution of Game Strategy and
Link Weight.
AB - In reality, the dependency relationship among individuals is heterogeneous and
time-varying. Based on this fact, we present a new mechanism of coevolution of
game strategy and link weight when analyzing the evolution of cooperation. In
detail, we model the population on a regular network, on which the relationship
between players is depicted by a weighted link, and prisoner's dilemma has been
applied to describe the interaction of players. Further, the impact of this
mechanism on the cooperative behavior has been outlined. By conducting large
scale Monte Carlo simulations, we can easily draw a conclusion that this
mechanism can promote cooperation efficiently. Compared with the traditional
case, when the temptation of defection b is large, the fraction of cooperation is
still able to keep in a high level. With a comprehensive examination of the
distribution of stable link weight, it is evident that the coevolution mechanism
would deviate the initial distribution. This mechanism induces the heterogeneity
of players, which enhances the fraction of cooperation. Numerical simulations
also indicate that an intermediate value of Delta/delta warrants an optimal
resolution of prisoner's dilemma. The mechanism of coevolution of game strategy
and link weight has a practical significance and will provide new insight for the
further research.
PMID- 26435189
TI - Systematic review of economic evaluations of vaccination programs in mainland
China: Are they sufficient to inform decision making?
AB - The purpose of the study was to systematically review economic evaluations of
vaccine programs conducted in mainland China. We searched for economic
evaluations of vaccination in China published prior to August 3, 2015 in eight
English-language and three Chinese-language databases. Each article was appraised
against the 19-item Consensus on Health Economic Criteria list (CHEC-list). We
found 23 papers evaluating vaccines against hepatitis B (8 articles),
Streptococcus pneumoniae (5 articles), human papillomavirus (3 articles),
Japanese encephalitis (2 articles), rotavirus (2 articles), hepatitis A (1
article), Enterovirus 71 (1 article) and influenza (1 article). Studies conformed
to a mean of 12 (range: 6-18) items in the CHEC-list criteria. Five of six
Chinese-language articles conformed to fewer than half of the 19 criteria items.
The main criteria that studies failed to conform to included: inappropriate
measurement (20 articles) and valuation (18 articles) of treatment and/or
vaccination costs, no discussion about distributional implications (18 articles),
missing major health outcomes (14 articles), no discussion about generalizability
to other contexts (14 articles), and inadequate sensitivity analysis (13
articles). In addition, ten studies did not include major cost components of
vaccination programs, and nine did not report outcomes in terms of life years
even in cases where QALYs or DALYs were calculated. Only 13 studies adopted a
societal perspective for analysis. All studies concluded that the appraised
vaccination programs were cost-effective except for one evaluation of universal 7
valent pneumococcal conjugate vaccine (PCV-7) in children. However, three of the
five studies on PCV-7 showed poor overall quality, and the number of studies on
vaccines other than hepatitis B vaccine and PCV-7 was limited. In conclusion,
major methodological flaws and reporting problems exist in current economic
evaluations of vaccination programs in China. Local guidelines for good practice
and reporting, institutional mechanisms and education may help to improve the
overall quality of these evaluations.
PMID- 26435190
TI - An enriched medical home intervention using community health workers improves
adherence to immunization schedules.
AB - IMPORTANCE: Disparities in childhood vaccination rates persist. OBJECTIVE: To
evaluate the impact of an enriched medical home intervention using community
health workers on improving immunization adherence among young children. DESIGN:
The intervention group received home visits from trained community health workers
to support families in adhering to recommended care while the comparison group
received usual care (i.e. no home visits/reminders). Immunization history and
socio-demographic data were collected using medical records and a validated
questionnaire. The doubly robust estimation of risk difference, which combines
weighting via propensity score and outcome regression model, was used to compare
immunization adherence rates between two groups. SETTING: Primary care practices
affiliated with a suburban tertiary care academic medical center serving a
socioeconomically diverse population. PARTICIPANTS: The study sample included
children <= 2 years of age at enrollment who crossed at least one age time point
of 3, 7, 15, or 24 months during their 6 months post-enrollment period. MAIN
OUTCOMES AND MEASURES: The primary outcome was age-specific immunization up-to
date status defined by CDC guidelines. The primary predictor was participation in
the intervention. RESULTS: The analysis included 201 children in the usual care
group and 110 children in the intervention group. The usual care and intervention
groups were divided into subgroups of newborn and infant/toddler to account for
prior immunization history. After adjusting for differences in group
characteristics, we found a significant absolute increase in the up-to-date
immunization likelihood for both newborns (20.9%, p=0.01) and infants/toddlers
(16.8%, p=0.01) receiving the intervention when compared to their peers receiving
usual clinical care. CONCLUSIONS AND RELEVANCE: Our findings demonstrate the
positive impact of an enriched medical home intervention using community health
worker home visitation on early childhood immunization up-to-date status. With
further study, this model may provide a cost-effective approach to improving
childhood vaccination rates, especially for vulnerable groups.
PMID- 26435191
TI - Functional roles of enhancer of zeste homolog 2 in gliomas.
AB - Gliomas are the most common and lethal type of primary malignant brain tumor. Due
to the infiltrative nature and high resistance to standard first line treatment
with combinations of radiation and chemotherapy, the prognosis of patient is very
poor. Recently, accumulated evidence suggests that enhancer of zeste homolog 2
(EZH2) serves as an oncogene and is involved in multiple glioma cell processes,
including cell cycle, invasion, glioma stem cell maintenance, drug and
radiotherapy resistance and so on. In this review, we will focus on updating
current knowledge of EZH2 in gliomas. Moreover, the regulation of EZH2 by
microRNAs and long non-coding RNAs and the therapeutic strategies targeting EZH2
for gliomas will also be discussed.
PMID- 26435192
TI - De novo transcriptome sequencing and discovery of genes related to copper
tolerance in Paeonia ostii.
AB - Paeonia ostii, an important ornamental and medicinal plant, grows normally on
copper (Cu) mines with widespread Cu contamination of soils, and it has the
ability to lower Cu contents in the Cu-contaminated soils. However, very little
molecular information concerned with Cu resistance of P. ostii is available. In
this study, high-throughput de novo transcriptome sequencing was carried out for
P. ostii with and without Cu treatment using Illumina HiSeq 2000 platform. A
total of 77,704 All-unigenes were obtained with a mean length of 710 bp. Of these
unigenes, 47,461 were annotated with public databases based on sequence
similarities. Comparative transcript profiling allowed the discovery of 4324
differentially expressed genes (DEGs), with 2207 up-regulated and 2117 down
regulated unigenes in Cu-treated library as compared to the control counterpart.
Based on these DEGs, Gene Ontology (GO) enrichment analysis indicated Cu stress
relevant terms, such as 'membrane' and 'antioxidant activity'. Meanwhile, Kyoto
Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis uncovered
some important pathways, including 'biosynthesis of secondary metabolites' and
'metabolic pathways'. In addition, expression patterns of 12 selected DEGs
derived from quantitative real-time polymerase chain reaction (qRT-PCR) were
consistent with their transcript abundance changes obtained by transcriptomic
analyses, suggesting that all the 12 genes were authentically involved in Cu
tolerance in P. ostii. This is the first report to identify genes related to Cu
stress responses in P. ostii, which could offer valuable information on the
molecular mechanisms of Cu resistance, and provide a basis for further genomics
research on this and related ornamental species for phytoremediation.
PMID- 26435193
TI - USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination.
AB - Ubiquitin modification of the TGF-beta pathway components is emerging as a key
mechanism of TGF-beta pathway regulation. To limit TGF-beta responses, TGF-beta
signaling is regulated through a negative feedback loop whereby the E3 ligase
SMURF2 targets the TGF-beta receptor (TbetaR) complex for ubiquitin-mediated
degradation. Counteracting this process, a number of deubiquitinating (DUBs)
enzymes have recently been identified that deubiquitinate and stabilize the
TbetaR. However the precise mechanism by which these DUBs act on TbetaR function
remains poorly defined. Here, we demonstrate that apart from targeting the TbetaR
complex directly, USP15 also deubiquitinates SMURF2 resulting in enhanced TbetaR
stability and downstream pathway activation. Through proteomic analysis, we show
that USP15 modulates the ubiquitination of Lys734, a residue required for SMURF2
catalytic activity. Our results show that SMURF2 is a critical target of USP15 in
the TGF-beta pathway and may also explain how USP15 and SMURF2 target multiple
complementary protein complexes in other pathways.
PMID- 26435195
TI - Noise in Graphene Superlattices Grown on Hexagonal Boron Nitride.
AB - Existing in almost all electronic systems, the current noise spectral density,
originated from the fluctuation of current, is by nature far more sensitive than
the mean value of current, the most common characteristic parameter in electronic
devices. Existing models on its origin of either carrier number or mobility are
adopted in practically all electronic devices. For the past few decades, there
has been no experimental evidence for direct association between 1/f noise and
any other kinetic phenomena in solid state devices. Here, in the study of a van
der Waals heterostructure of graphene on hexagonal BN superlattice, satellite
Dirac points have been characterized through 1/f noise spectral density with
pronounced local minima and asymmetric magnitude associated with its unique
energy dispersion spectrum, which can only be revealed by scanning tunneling
microscopy and low temperature magneto-transport measurement. More importantly,
these features even emerge in the noise spectra of devices showing no minima in
electric current, and are robust at all temperatures down to 4.3 K. In addition,
graphene on h-BN exhibits a record low noise level of 1.6 * 10(-9) MUm(2) Hz(-1)
at 10 Hz, more than 1 order of magnitude lower than previous results for graphene
on SiO2. Such an epitaxial van der Waals material system not only enables an
unprecedented characterization of fundamentals in solids by 1/f noise, but its
superior interface also provides a key and feasible solution for further
improvement of the noise level for graphene devices.
PMID- 26435194
TI - Plasma membrane restricted RhoGEF activity is sufficient for RhoA-mediated actin
polymerization.
AB - The small GTPase RhoA is involved in cell morphology and migration. RhoA activity
is tightly regulated in time and space and depends on guanine exchange factors
(GEFs). However, the kinetics and subcellular localization of GEF activity
towards RhoA are poorly defined. To study the mechanism underlying the
spatiotemporal control of RhoA activity by GEFs, we performed single cell imaging
with an improved FRET sensor reporting on the nucleotide loading state of RhoA.
By employing the FRET sensor we show that a plasma membrane located RhoGEF,
p63RhoGEF, can rapidly activate RhoA through endogenous GPCRs and that localized
RhoA activity at the cell periphery correlates with actin polymerization.
Moreover, synthetic recruitment of the catalytic domain derived from p63RhoGEF to
the plasma membrane, but not to the Golgi apparatus, is sufficient to activate
RhoA. The synthetic system enables local activation of endogenous RhoA and
effectively induces actin polymerization and changes in cellular morphology.
Together, our data demonstrate that GEF activity at the plasma membrane is
sufficient for actin polymerization via local RhoA signaling.
PMID- 26435196
TI - Effects of Agar Gel Strength and Fat on Oral Breakdown, Volatile Release, and
Sensory Perception Using in Vivo and in Vitro Systems.
AB - The density and composition of a food matrix affect the rates of oral breakdown
and in-mouth flavor release as well as the overall sensory experience. Agar gels
of increasing concentration (1.0, 1.7, 2.9, and 5% agarose) with and without
added fat (0, 2, 5, and 10%) were spiked with seven aroma volatiles. Differences
in oral processing and sensory perception were systematically measured by a
trained panel using a discrete interval time intensity method. Volatile release
was measured in vivo and in vitro by proton transfer reaction mass spectrometry.
Greater oral processing was required as agar gel strength increased, and the
intensity of flavor-related sensory attributes decreased. Volatile release was
inversely related to gel strength, showing that physicochemical phenomena were
the main mechanisms underlying the perceived sensory changes. Fat addition
reduced the amount of oral processing and had differential effects on release,
depending on the fat solubility or lipophilicity of the volatiles.
PMID- 26435197
TI - Hofmeister effect of anions on calcium translocation by sarcoplasmic reticulum
Ca(2+)-ATPase.
AB - The occurrence of Hofmeister (specific ion) effects in various membrane-related
physiological processes is well documented. For example the effect of anions on
the transport activity of the ion pump Na(+), K(+)-ATPase has been investigated.
Here we report on specific anion effects on the ATP-dependent Ca(2+)
translocation by the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA). Current
measurements following ATP concentration jumps on SERCA-containing vesicles
adsorbed on solid supported membranes were carried out in the presence of
different potassium salts. We found that monovalent anions strongly interfere
with ATP-induced Ca(2+) translocation by SERCA, according to their increasing
chaotropicity in the Hofmeister series. On the contrary, a significant increase
in Ca(2+) translocation was observed in the presence of sulphate. We suggest that
the anions can affect the conformational transition between the phosphorylated
intermediates E1P and E2P of the SERCA cycle. In particular, the stabilization of
the E1P conformation by chaotropic anions seems to be related to their adsorption
at the enzyme/water and/or at the membrane/water interface, while the more
kosmotropic species affect SERCA conformation and functionality by modifying the
hydration layers of the enzyme.
PMID- 26435198
TI - Upregulation of 14-3-3 eta in chronic liver fluke infection is a potential
diagnostic marker of cholangiocarcinoma.
AB - PURPOSE: To discover protein markers in chronic/advanced opisthorchiasis for the
early detection of Opisthorchis viverrini (OV)-associated cholangiocarcinoma
(CCA). EXPERIMENTAL DESIGN: Liver tissues derived from normal hamsters and those
with chronic/advanced opisthorchiasis (n = 5 per group) were subjected to 2DE and
LC-MS/MS. Candidate protein expression was confirmed in hamster models and human
CCA tissue microarray (TMA) using immunohistochemistry and Western blot. RESULT:
Proteomics analysis detected 14-3-3 eta only in infected hamsters, not in
uninfected controls. Immunohistochemistry and Western blot analysis confirmed low
expression of 14-3-3 eta in normal hamster livers and demonstrated increased
expression through time in infected livers. This protein was also observed in
parasite organs, especially during the chronic phase of opisthorchiasis.
Moreover, increased expression of 14-3-3 eta, relative to normal hamster livers,
was observed during the early stage of CCA induced by OV infection and
administration of N-nitrosodimethylamine. Immunohistochemical analysis of human
TMA revealed that 14-3-3 eta was highly expressed in CCA (84.23%, 187/222 cases)
but was not found in hepatocellular carcinoma or healthy liver tissues.
CONCLUSIONS AND CLINICAL RELEVANCE: 14-3-3 eta protein has potential as a
screening and early diagnostic marker for CCA.
PMID- 26435199
TI - Knowledge and attitudes regarding clinical trials and willingness to participate
among prostate cancer patients.
AB - BACKGROUND: Enrollment of minorities in clinical trials remains low. Through a
California population-based study of men with early stage prostate cancer, we
examined the relationships between race/ethnicity and 1) attitudes, 2) knowledge
and 3) willingness to participate in clinical trials. METHODS: From November 2011
November 2012, we identified all incident cases of prostate cancer in African
American, Latino, and Asian American men ages 18-75 years, and a random sample of
white men diagnosed in 2008, through the California Cancer Registry, living
within 60 miles of a site offering >= 1 clinical trial. Participants completed a
30-min telephone interview in English, Spanish, or Chinese. In this cross
sectional population-based study, multivariable logistic regression was used to
estimate associations between race/ethnicity and 1) attitudes, 2) knowledge and
3) willingness to participate. RESULTS: Of 855 participants, 52% were >= 65
years, 42% were white, 24% Latino, 19% African American and 15% Asian American.
The majority (81%) had medium-to-high health literacy. Compared to non-Latino
white men, African American men were less likely to have above average knowledge
of clinical trials (OR=0.55; CI=0.35-0.86), as were Asian American (OR=0.55;
CI=0.33-0.93) and Latino men (OR=0.30; CI=0.18-0.48). There were no racial/ethnic
differences in willingness to participate. The attitude that "researchers are the
main beneficiaries" was negatively associated with willingness (OR=0.63; CI=0.43
0.93); the attitude that "patients are the main beneficiaries" was positively
associated with willingness to participate (OR=1.57; CI=1.07-2.29). CONCLUSIONS:
Men with early stage prostate cancer are willing to take part in clinical trials
and this willingness does not vary by race/ethnicity.
PMID- 26435200
TI - Treatment preference and patient centered prostate cancer care: Design and
rationale.
AB - Prostate cancer is a slow progressing cancer that affects millions of men in the
US. Due to uncertainties in outcomes and treatment complications, it is important
that patients engage in informed decision making to choose the "optimal
treatment". Patient centered care that encompasses informed decision-making can
improve treatment choice and quality of care. Thus, assessing patient treatment
preferences is critical for developing an effective decision support system. The
objective of this patient-centered randomized clinical trial was to study the
comparative effectiveness of a conjoint analysis intervention compared to usual
care in improving subjective and objective outcomes in prostate cancer patients.
We identified preferred attributes of alternative prostate cancer treatments that
will aid in evaluating attributes of treatment options. In this two-phase study,
in Phase 1 we used mixed methods to develop an adaptive conjoint task instrument.
The conjoint task required the patients to trade-off attributes associated with
treatments by assessing their relative importance. Phase 2 consisted of a
randomized controlled trial of men with localized prostate cancer. We analyzed
the effect of conjoint task intervention on the association between preferences,
treatment and objective and subjective outcomes. Our conjoint task instrument can
lead to a values-based patient-centered decision aid tool and help tailor
treatment decision making to the values of prostate cancer patients. This will
ultimately improve clinical decision making, clinical policy process, enhance
patient centered care and improve prostate cancer outcomes.
PMID- 26435201
TI - Highly Dispersed Ultrafine Pt Nanoparticles on Reduced Graphene Oxide Nanosheets:
In Situ Sacrificial Template Synthesis and Superior Electrocatalytic Performance
for Methanol Oxidation.
AB - We report a simple and environmentally friendly route to prepare platinum/reduced
graphene oxide (Pt/rGO) nanocomposites (NCs) with highly reactive MnOx colloids
as reducing agents and sacrificial templates. The colloids are obtained by laser
ablation of a metallic Mn target in graphene oxide (GO)-containing solution.
Structural and morphological investigations of the as-prepared NCs revealed that
ultrafine Pt nanoparticles (NPs) with an average size of 1.8 (+/-0.6) nm are
uniformly dispersed on the surfaces of rGO nanosheets. Compared with commercial
Pt/C catalysts, Pt/rGO NCs with highly electrochemically active surface areas
show remarkably improved catalytic activity and durability toward methanol
oxidation. All of these superior characteristics can be attributed to the small
particle size and uniform distribution of the Pt NPs, as well as the excellent
electrical conductivity and stability of the rGO catalyst support. These findings
suggest that Pt/rGO electrocatalysts are promising candidate materials for
practical use in fuel cells.
PMID- 26435202
TI - Predictive value of red blood cell distribution width for coronary artery lesions
in patients with Kawasaki disease.
AB - Recent studies have shown that elevated red blood cell distribution width is
associated with poor outcome in cardiovascular diseases. In order to assess the
predictive value of red blood cell distribution width, before treatment with
intravenous immunoglobulins, for coronary artery lesions in patient with Kawasaki
disease, we compared 83 patients with coronary artery lesions and 339 patients
without coronary artery lesions before treatment with intravenous immunoglobulin.
Clinical, echocardiographic, and biochemical values were evaluated along with red
blood cell distribution width. A total of 422 consecutive patients with Kawasaki
disease were enrolled into our study. According to receiver operating
characteristic curve analysis, the optimal red blood cell distribution width cut
off value for predicting coronary artery lesions was 14.55% (area under the curve
was 0.721; p=0.000); eighty-three patients (19.7%) had coronary artery lesions,
and 70% of the patients with coronary artery lesions had red blood cell
distribution width level >14.55%. Logistic regression analysis revealed that
fever duration >14 days (odds ratio was 3.42, 95% confidence interval was 1.27
9.22; p=0.015), intravenous immunoglobulin resistance (odds ratio was 2.33, 95%
confidence interval was 1.02-5.29; p=0.04), and red blood cell distribution width
>14.55% (odds ratio was 3.49, 95% confidence interval was 2.01-6.05; p=0.000)
were independent predictors of coronary artery lesions in patients with Kawasaki
disease. In Conclusion, red blood cell distribution width may be helpful for
predicting coronary artery lesions in patients with Kawasaki disease.
PMID- 26435203
TI - Optical and surface properties of optically transparent Li3 PO4 solid electrolyte
layer for transparent solid batteries.
AB - In this study, optical and surface properties of the optically transparent Li3
PO4 solid electrolyte layer for transparent solid battery have been investigated
for the first time. To determine the optical properties, transmittance,
absorbance, reflection, refractive index spectra, and optical band gap were
determined by UV-Vis spectrophotometer and optical interferometer. The surface
property of the transparent Li3 PO4 solid electrolyte was analyzed using atomic
force microscopy. One another important parameter is contact angle (CA) surface
free energy (SFE). CA and SFE were determined by optical tensiometer. These
values probably are a most important parameter for polymer and hybrid battery
performance. For the best performance, value of CA should be low. As a result,
solid electrolyte layer is a highly transparent and it has a high wettability.
SCANNING 38:317-321, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26435204
TI - Mesoporous Silica Nanoparticles with pH-Sensitive Nanovalves for Delivery of
Moxifloxacin Provide Improved Treatment of Lethal Pneumonic Tularemia.
AB - We have optimized mesoporous silica nanoparticles (MSNs) functionalized with pH
sensitive nanovalves for the delivery of the broad spectrum fluoroquinolone
moxifloxacin (MXF) and demonstrated its efficacy in treating Francisella
tularensis infections both in vitro and in vivo. We compared two different
nanovalve systems, positive and negative charge modifications of the mesopores,
and different loading conditions-varying pH, cargo concentration, and duration of
loading-and identified conditions that maximize both the uptake and release
capacity of MXF by MSNs. We have demonstrated in macrophage cell culture that the
MSN-MXF delivery platform is highly effective in killing F. tularensis in
infected macrophages, and in a mouse model of lethal pneumonic tularemia, we have
shown that the drug-loaded MSNs are much more effective in killing F. tularensis
than an equivalent amount of free MXF.
PMID- 26435205
TI - The association between platelet transfusion and idiopathic pneumonia syndrome is
unaffected by platelet product type.
AB - BACKGROUND: Methods used to produce platelet (PLT) components, pooling of PLT
rich plasma (PRP-PLT) and apheresis (AP-PLT), may variably contribute to the
pathogenesis and severity of idiopathic pneumonia syndrome (IPS). STUDY DESIGN
AND METHODS: We performed a retrospective cohort study of 906 allogeneic
hematopoietic cell transplant recipients to examine associations between PLT
product type and risks of developing IPS and dying after IPS onset. Proportional
hazards models included separate terms for the sum of all PLT transfusions and
the sum of PRP-PLT units received in the 3 or 7 days before IPS onset. Similarly
constructed models analyzed the outcome of time to death after IPS onset. All
analyses were adjusted for known IPS risk factors. RESULTS: Patients received a
median of three PRP-PLT transfusions (interquartile range [IQR], 0-6) and five AP
PLT transfusions (IQR, 1-13) while at risk for IPS. Seventy-five patients (8%)
developed IPS by Posttransplant Day 120. The proportion of PRP-PLT transfusions
was not associated with risk of developing IPS (3-day hazard ratio [HR] 0.98, 95%
CI 0.74-1.29, p = 0.86; 7-day HR 1.00, 95% CI 0.86-1.15, p = 0.95) or dying after
IPS onset (3-day HR 0.99, 95% CI 0.75-1.31, p = 0.97; 7-day HR 0.98, 95% CI 0.78
1.12, p = 0.47). CONCLUSION: The association between PLT transfusions and risk of
developing IPS or dying after IPS onset does not differ according to PLT product
type. Further research is required to identify potentially modifiable steps in
PLT component production that contribute to IPS.
PMID- 26435206
TI - Trends Form Follows Function: New Ways to Inform and Inspire.
PMID- 26435207
TI - Trying to Drink from a Fire Hose: Too Much of the Wrong Kind of Health Care News.
PMID- 26435208
TI - Biologic Approaches to Treat Substance-Use Disorders.
AB - In contrast to traditional pharmacodynamic approaches to treat substance-use
disorders (SUDs), the use of biologics (vaccines, monoclonal antibodies, and
genetically modified enzymes) is based on a pharmacokinetic principle: reduce the
amount of (and, ideally, eliminate) abused drug entering the central nervous
system (CNS). Preclinical studies indicate that biologics are effective in both
facilitating abstinence and preventing relapse to abused substances ranging from
nicotine to heroin. While data are still emerging, the results from multiple
clinical trials can best be described as mixed. Nonetheless, these clinical
studies have already provided important insights using 'first-generation' tools
that may inform the development of effective and commercially viable biologics to
treat tobacco-, cocaine-, and methamphetamine-use disorders.
PMID- 26435209
TI - Gatekeepers Controlling GPCR Export and Function.
AB - Regulated export of G protein-coupled receptors (GPCRs) from intracellular stores
involves chaperones and escort proteins, which promote their progression to the
cell surface, and gatekeepers, which retain them in intracellular compartments.
Functional gamma-aminobutyric acid (GABA)B receptors, the paradigm of this
phenomenon, comprise GB1 and GB2 subunits forming a heterodimer. GB1 is retained
in the endoplasmic reticulum (ER) in the absence of GB2. A specific ER-resident
gatekeeper, prenylated Rab acceptor family 2 (PRAF2), is involved in GB1
retention and prevents its progression into the biosynthetic pathway. GB1 can be
released from PRAF2 only on competitive interaction with GB2. PRAF2 is ubiquitous
and belongs to a subgroup of the mammalian Ypt-interacting protein (Yip) family.
Several other GPCRs are likely to be regulated by Yip proteins, which might be
involved in the pathophysiology of human diseases that are associated with
impaired receptor targeting to the cell surface.
PMID- 26435211
TI - Protein Tyrosine Phosphatases in Hypothalamic Insulin and Leptin Signaling.
AB - The hypothalamus is critical to the coordination of energy balance and glucose
homeostasis. It responds to peripheral factors, such as insulin and leptin, that
convey to the brain the degree of adiposity and the metabolic status of the
organism. The development of leptin and insulin resistance in hypothalamic
neurons appears to have a key role in the exacerbation of diet-induced obesity.
In rodents, this has been attributed partly to the increased expression of the
tyrosine phosphatases Protein Tyrosine Phosphatase 1B (PTP1B) and T cell protein
tyrosine phosphatase (TCPTP), which attenuate leptin and insulin signaling.
Deficiencies in PTP1B and TCPTP in the brain, or specific neurons, promote
insulin and leptin signaling and prevent diet-induced obesity, type 2 diabetes
mellitus (T2DM), and fatty liver disease. Although targeting phosphatases and
hypothalamic circuits remains challenging, recent advances indicate that such
hurdles might be overcome. Here, we focus on the roles of PTP1B and TCPTP in
insulin and leptin signaling and explore their potential as therapeutic targets.
PMID- 26435210
TI - Therapeutic Targeting of Siglecs using Antibody- and Glycan-Based Approaches.
AB - The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of
immunomodulatory receptors whose functions are regulated by their glycan ligands.
Siglecs are attractive therapeutic targets because of their cell type-specific
expression pattern, endocytic properties, high expression on certain
lymphomas/leukemias, and ability to modulate receptor signaling. Siglec-targeting
approaches with therapeutic potential encompass antibody- and glycan-based
strategies. Several antibody-based therapies are in clinical trials and continue
to be developed for the treatment of lymphoma/leukemia and autoimmune disease,
while the therapeutic potential of glycan-based strategies for cargo delivery and
immunomodulation is a promising new approach. Here we review these strategies
with special emphasis on emerging approaches and disease areas that may benefit
from targeting the Siglec family.
PMID- 26435212
TI - Apolipoprotein C-III: From Pathophysiology to Pharmacology.
AB - Apolipoprotein C-III (apoC-III) has a critical role in the metabolism of
triglyceride (TG)-rich lipoproteins (TRLs). Animal models lacking the APOC3 gene
exhibit reduced plasma TG levels, whereas the overexpression of APOC3 leads to
increased TG levels. In humans, loss-of-function mutations in APOC3 are
associated with reduced plasma TG levels and reduced risk for ischemic vascular
disease and coronary heart disease. Several hypolipidemic agents have been shown
to reduce apoC-III, including fibrates and statins, and antisense technology
aimed at inhibiting APOC3 mRNA to decrease the production of apoC-III is
currently in Phase III of clinical development. Here, we review the
pathophysiological role of apoC-III in TG metabolism and the evidence supporting
this apolipoprotein as an emerging target for hypertriglyceridemia (HTG) and
associated cardiovascular disorders.
PMID- 26435213
TI - Ligands for the Nuclear Peroxisome Proliferator-Activated Receptor Gamma.
AB - Nuclear receptors are ligand-activated transcription factors, which represent a
primary class of drug targets. The nuclear receptor peroxisome proliferator
activated receptor gamma (PPARgamma) is a key player in various biological
processes. PPARgamma is widely known as the target protein of the
thiazolidinediones for treating type 2 diabetes. Moreover, PPARgamma ligands can
induce anti-inflammatory and potentially additional beneficial effects. Recent
mechanistic insights of PPARgamma modulation give hope the next generation of
efficient PPARgamma-based drugs with fewer side effects can be developed.
Furthermore, chemical approaches that make use of synergistic action of
combinatorial ligands are promising alternatives for providing tailored medicine.
Lessons learned from fine-tuning the action of PPARgamma can provide avenues for
efficient molecular intervention via many other nuclear receptors to combat
common diseases.
PMID- 26435214
TI - Silent information regulator 1 (SIRT1) ameliorates liver fibrosis via promoting
activated stellate cell apoptosis and reversion.
AB - SIRT1 (silent information regulator 1), a conserved NAD+-dependent histone
deacetylase, is closely related with various biological processes. Moreover, the
important role of SIRT1 in alcoholic liver disease, nonalcoholic fatty liver and
HCC had been widely reported. Recently, a novel role of SIRT1 was uncovered in
organ fibrosis diseases. Here, we investigated the inhibitory effect of SIRT1 in
liver fibrogenesis. SIRT1 protein was dramatically decreased in CCl4-treated mice
livers. Stimulation of LX-2 cells with TGF-beta1 also resulted in a significant
suppression of SIRT1 protein. Nevertheless, TGF-beta1-induced LX-2 cell
activation was inhibited by SIRT1 plasmid, and this was accompanied by up
regulation of cell apoptosis-related proteins. Overexpression of SIRT1 also
attenuated TGF-beta1-induced expression of myofibroblast markers alpha-SMA and
COL1a. However, the important characteristic of the recovery of liver fibrosis is
not only the apoptosis of activated stellate cells but also the reversal of the
myofibroblast-like phenotype to a quiescent-like phenotype. Restoration of SIRT1
protein was observed in the in vivo spontaneously liver fibrosis reversion model
and in vitro MDI (isobutylmethylxanthine, dexamethasone, and insulin)-induced
reversed stellate cells, and forced expression of SIRT1 also promoted the
reversal of activated stellate cells. Furthermore, lncRNA MALAT1 (metastasis
associated lung adenocarcinoma transcript 1) was increased in liver fibrosis.
RNAi-mediated suppression of MALAT1 resulted in a decrease of myofibroblast
markers and restoration of SIRT1 protein. These observations suggested that SIRT1
contributed to apoptosis and reversion of activated LX-2 cells and SIRT1 might be
regulated by MALAT1 in liver fibrosis. Therefore, SIRT1 could be considered as a
valuable therapeutic target for translational studies of liver fibrosis.
PMID- 26435216
TI - Evaluation of different pig oral mucosa sites as permeability barrier models for
drug permeation studies.
AB - The objective of the present study was to investigate the influence of
preparation and storage conditions on the histology and permeability of different
parts of porcine oral mucosa used for in vitro studies of transbuccal
formulations. Fresh and frozen (-20 degrees C and -80 degrees C, with or without
cryoprotectant) epithelia of porcine palatal, gingival, dorsum of the tongue, and
buccal mucosa were submitted for histological analyses to determine the effects
of storage conditions on barrier integrity. Permeation of lidocaine hydrochloride
(used as a hydrophilic model drug) across fresh and previously frozen oral
epithelium was measured in order to evaluate the barrier function. Histological
evaluation demonstrated that the oral epithelium was successfully separated from
the connective tissue, except for gingival mucosa. After storage under different
conditions, all tissues presented desquamation of superficial layers and
spherical spaces induced by the freezing process. The permeability of lidocaine
hydrochloride varied among the fresh oral mucosa and generally increased after
freezing. In conclusion, fresh epithelium from the buccal and dorsum of the
tongue mucosa should be used for in vitro studies investigating hydrophilic drug
transport when these are the desired clinical application sites. However, when
the palate is the target site, both fresh and frozen (for up to 4weeks, without
addition of cryoprotectant) samples could be used. The addition of glycerol as a
cryoprotectant should be avoided due to increased lidocaine hydrochloride
permeability.
PMID- 26435215
TI - Site specific modification of the human plasma proteome by methylglyoxal.
AB - Increasing evidence identifies dicarbonyl stress from reactive glucose
metabolites, such as methylglyoxal (MG), as a major pathogenic link between
hyperglycemia and complications of diabetes. MG covalently modifies arginine
residues, yet the site specificity of this modification has not been thoroughly
investigated. Sites of MG adduction in the plasma proteome were identified using
LC-MS/MS analysis in vitro following incubation of plasma proteins with MG.
Treatment of plasma proteins with MG yielded 14 putative MG hotspots from five
plasma proteins (albumin [nine hotspots], serotransferrin, haptoglobin [2
hotspots], hemopexin, and Ig lambda-2 chain C regions). The search results
revealed two versions of MG-arginine modification, dihydroxyimidazolidine (R+72)
and hydroimidazolone (R+54) adducts. One of the sites identified was R257 in
human serum albumin, which is a critical residue located in drug binding site I.
This site was validated as a target for MG modification by a fluorescent probe
displacement assay, which revealed significant drug dissociation at 300 MUM MG
from a prodan-HSA complex (75 MUM). Moreover, twelve human plasma samples (six
male, six female, with two type 2 diabetic subjects from both genders) were
analyzed using multiple reaction monitoring (MRM) tandem mass spectrometry and
revealed the presence of the MG-modified albumin R257 peptide. These data provide
insights into the nature of the site-specificity of MG modification of arginine,
which may be useful for therapeutic treatments that aim to prevent MG-mediated
adverse responses in patients.
PMID- 26435217
TI - Towards a test to predict 5-fluorouracil toxicity: Pharmacokinetic data for
thymine and two sequential metabolites following oral thymine administration to
healthy adult males.
AB - The fluoropyrimidine drugs 5-fluorouracil and its oral prodrug capecitabine
remain first line therapy for solid tumours of the neck, breast and colon.
However, significant and unpredictable toxicity affects about 10-25% of patients
depending upon the mode of 5-fluorouracil delivery. The pharmacokinetics of
thymine (5-methyluracil) may provide an approach for screening for 5-fluorouracil
toxicity, based on the rationale that thymine is a close structural analogue of 5
fluorouracil and is catabolized by the same enzymatic pathway. Oral thymine
loading tests were performed on 12 healthy volunteers. Each subject was given a
single oral dose of 250mg thymine in capsule form. Blood, urine and saliva
samples were collected pre-dose and up to 5h post-dose. Concentrations of
thymine, and its catabolites dihydrothymine and beta-ureidoisobutyrate were
analysed by HPLC-tandem mass spectrometry in plasma, urine and saliva. The
pharmacokinetic data of healthy volunteers were analysed assuming a non
compartmental model. Thymine peaked quickly (30-45min) in plasma to a maximum
concentration of 170+/-185MUg/L (mean+/-SD). Clearance was high (mean 57.9L/h/kg)
exceeding normal human liver blood flow, suggesting low systemic bioavailability;
urinary recovery of the thymine dose was low (<1%). Apparent formation rate
limited kinetics were observed for dihydrothymine, and the plasma concentration
of dihydrothymine was consistently 10-fold higher than that of thymine. Plasma
beta-ureidoisobutyrate concentrations, on the other hand, were similar to that of
thymine. Genotyping confirmed that pathological mutations of the DPYD gene were
absent. The urinary excretion ratio of thymine/dihydrothymine was informative of
the maximum concentration. Saliva thymine was highly variable. These data are
potentially useful as a basis for developing of a screening procedure to
prospectively identify patients who are at risk of toxicity from fluoropyrimidine
drugs.
PMID- 26435218
TI - Isolation and characterization of three cadmium-inducible promoters from Oryza
sativa.
AB - Cadmium (Cd) is an important soil pollutant. Developing genetically engineered
crops might be a feasible strategy for Cd decontamination and damage prevention.
Both genes and promoters are critical for the effective construction of
genetically modified plants. Although many functional genes for Cd tolerance and
accumulation have been identified, few reports have focused on plant Cd-inducible
promoters. Here, we identified three Cd-inducible genes in the rice genome: two
tau class glutathione S-transferase (GSTU) genes, OsGSTU5 and OsGSTU37, and an
HSP20/alpha crystallin family protein gene, OsHSP18.6. The promoter sequences
were isolated and tested in transgenic rice lines using a GUSplus reporter gene.
All of the promoters exhibited low background expression under normal conditions
and could be strongly induced by Cd stress. Although their strength was
comparable to that of the constitutive OsACTIN promoter under Cd stress, their
time-dependent expression patterns under both short- and long-term Cd exposure
were markedly different. The responses of the three promoters to other heavy
metals were also examined. Furthermore, heavy metal-responsive cis elements in
the promoters were computationally analyzed, and regions determining the Cd
stress response were analyzed using a series of truncations. Our results indicate
that the three Cd-inducible rice promoters described herein could potentially be
used in applications aimed at improving heavy metal tolerance in crops or for the
bio-monitoring of environmental contamination.
PMID- 26435219
TI - Emulating human microcapillaries in a multi-organ-chip platform.
AB - Current microfluidic chip-based tissue culture systems lack a capillary
endothelial vessel system, which would enable perfusion with blood. We utilise
spatial cell cultures to populate a perfused multi-organ-chip platform-a
microfluidic device recently introduced for substance testing. Complete
biological vascularization of such culture systems is vital to properly emulate
physiological tissue behaviour. In this study, we incorporated a fibrin scaffold
into the two-organ-chip design. Herein, adipose-derived stromal cells (ASCs)
directed human umbilical vein endothelial cells (HUVECs) to organise into tube
like structures. The ASCs induced tube formation of HUVECs in static and dynamic
conditions. The replacement of full medium enriched with growth factors and
foetal calf serum with basal medium resulted in viable cells with similar gene
expression profiles. We regard this as a prerequisite for studies with organ
constructs that have a need for a different medium formulation. Furthermore, we
here address stability issues of the fibrin gel and fibrin composition for
optimal microvessel formation.
PMID- 26435221
TI - Reply to: Improving Research Standards to Restore Trust in Intranasal Oxytocin.
PMID- 26435220
TI - Homology analysis and cross-immunogenicity of OmpA from pathogenic Yersinia
enterocolitica, Yersinia pseudotuberculosis and Yersinia pestis.
AB - The outer membrane protein A (OmpA) is one of the intra-species conserved
proteins with immunogenicity widely found in the family of Enterobacteriaceae.
Here we first confirmed OmpA is conserved in the three pathogenic Yersinia:
Yersinia pestis, Yersinia pseudotuberculosis and pathogenic Yersinia
enterocolitica, with high homology at the nucleotide level and at the amino acid
sequence level. The identity of ompA sequences for 262 Y. pestis strains, 134 Y.
pseudotuberculosis strains and 219 pathogenic Y. enterocolitica strains are 100%,
98.8% and 97.7% similar. The main pattern of OmpA of pathogenic Yersinia are
86.2% and 88.8% identical at the nucleotide and amino acid sequence levels,
respectively. Immunological analysis showed the immunogenicity of each OmpA and
cross-immunogenicity of OmpA for pathogenic Yersinia where OmpA may be a vaccine
candidate for Y. pestis and other pathogenic Yersinia.
PMID- 26435222
TI - Psychiatrists' Attitudes Toward Transcranial Magnetic Stimulation.
PMID- 26435223
TI - Improving Research Standards to Restore Trust in Intranasal Oxytocin.
PMID- 26435224
TI - The local knowledge of medicinal plants trader and diversity of medicinal plants
in the Kabanjahe traditional market, North Sumatra, Indonesia.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Market is the main place for transactions of
medicinal plants and traditional ingredients by local community in the Karo
regency, North Sumatra, Indonesia. This is the first study to document the local
knowledge of traders on and the diversity of the medicinal plants. The
investigation was carried out in the Kabanjahe traditional market, in the Karo
regency. The research goal was to reveal the local knowledge, diversity and
utilization of medicinal plants, which have been traded in the Kabanjahe
traditional market, as a basis for conservation efforts. MATERIALS AND METHODS:
The study was conducted through ethnobotanical approach using market surveys. All
traders of medicinal plants were surveyed applying in-depth interviews and
participative observations. Data were analyzed qualitatively using descriptive
statistics. The diversity of medicinal plants was expressed in term of the
Shannon-Wiener diversity index (H'), whereas the similarity among traders was
indicated by Jaccard index (Ji). RESULTS: Traders of medicinal plants stored the
simplicia of medicinal plants in chest of drawers, plastic baskets, plastic bags,
and in the air by suspending them from the the stall ceilings. We recorded 344
species, 217 genera and 90 families of medicinal plants. Those that were sold
mostly belong to Zingeberaceae (20 species), Poaceae (19 species), and
Asclepiadaceae (17 species), and the species received high consumers demand,
mostly belong to Zingiberaceae, Rutaceae, and Asclepidiaceae. Asclepidiaceae was
used to treat diseases like cancer and heart problems. The Shannon-Wiener
diversity index of medicinal plants at the Kabanjahe traditional market was high
(H'= 5.637). The high Jaccard similarity index (Ji>0.56) suggested that the
traders were trading similar species of medicinal plants. CONCLUSION: Kabanjahe
traditional market is the center for the sale of of medicinal plants as
traditional ingredients. Several species are well known for their pharmacological
properties but others, [such as: Dischidia imbricata (Blume) Steud., Dischidia
nummularia R.Br., Hoya macrophylla Blume, and Hoya coriacea Blume] have been used
for cancer treatment by local communities, but pharmacologically unknown, hence
they are promising candidates for further investigation.
PMID- 26435226
TI - Tension band plating in growth modulation : A review of current evidences.
AB - Tension band plating (TBF) has been pitted as the best method for correcting the
angular deformities and limb length discrepancies (LLD) in growing children. In
this review we examined the superiority of the tension band plating over other
methods of growth modulation, in terms of safety and efficacy. As per the current
literature, in angular deformities TBP has similar correction rates with lesser
complications. However in LLD the results are less promising.
PMID- 26435225
TI - Tetramethylpyrazine identified by a network pharmacology approach ameliorates
methotrexate-induced oxidative organ injury.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tetramethylpyrazine (TMP) is one of the active
constituents extracted from a frequently used herb, Ligusticum wallichii Franchat
(Chuan-Xiong in Chinese), in traditional Chinese medicine. TMP can exert multiple
pharmacological actions such as anti-inflammatory, anti-oxidative damage, anti
platelet and neuroprotective effects, and its applications deserve further
explored. AIM OF THE STUDY: This study aimed to determine the new role of TMP
identified by a network pharmacology approach to alleviate the methotrexate (MTX)
induced oxidative injury and characterize their mechanism of combinational
actions. MATERIALS AND METHODS: A network pharmacology-based screening strategy
is applied for target profile prediction and pharmacological characterization of
herbal compounds, which is used to guide the following in vitro and in vivo
experiments. The effect of herbal compounds identified by network pharmacology
approaches to reduce the toxicity of MTX was assessed by MTX-induced rat toxicity
model. The potential targets of TMP in this study were evaluated using standard
protocols provided by Cerep, Inc. RESULTS: This strategy identified TMP from
Ligusticum wallichii Franchat as a potent compound for ameliorating the oxidative
organ injury of MTX. According to the predicted target profiles of TMP, a
possible mechanism of the abrogation of MTX-induced toxicity is that TMP could
upregulate cAMP by inhibiting phosphodiesterase (PDE) 10A2 activity. Another
novel finding is that the competitive binding and antagonistic effects of TMP on
adenosine receptor 2A and 2B appear to play important roles in the TMP-mediated
reversal of MTX-induced hepatic injury. CONCLUSION: TMP identified by a network
pharmacology approach could ameliorate MTX-induced oxidative organ injury. This
study provides important evidence for the preclinical evaluation of TMP and MTX
as a novel combinatorial remedy.
PMID- 26435227
TI - Internal fixation of femoral neck stress fractures in young female athletes with
a dynamic locking plate.
AB - PURPOSE: Displaced stress fractures of the femoral neck in young female athletes
are a rare but a difficult injury to treat with a favourable outcome, as there is
a reported high incidence of avascular necrosis. Traditionally they are
internally fixed with either cannulated screws or a sliding hip screw. Our study
aims to highlight the Targon Femoral Neck (FN, B-Braun, Aesculap Inc, Germany)
implant as a safe alternative for fixation of these injuries. METHODS: Three
consecutive young female recreational athletes were reviewed from our institution
with a displaced stress fracture of the femoral neck treated with the dynamic
locking plate. RESULTS: Two patients achieved good results with full union and no
complications. One patient had a poor result as she developed avascular necrosis
5 months post-operatively requiring revision to a total hip arthroplasty.
CONCLUSION: Our study highlights the Targon FN implant is a safe alternative for
internal fixation of displaced stress fractures of the femoral neck in young
female recreational athletes.
PMID- 26435228
TI - The role of external fixators in paediatric trauma.
AB - We report a retrospective review of all paediatric trauma patients managed with
an external fixator admitted to our institution over a 7-year period. We
identified 30 fractures in 28 children. The fractures included 20 tibiae, 5
femurs, 2 humerii, 2 radii and 1 phalanx. The indications were 23 open fractures,
4 comminuted fractures and 3 closed fractures in poly-traumatised patients. It
was the definitive treatment in 13 fractures. The mean length of total time with
an external fixator was 9.6 weeks (range 1-38 weeks.) Difficulties encountered
were eight problems, one obstacle and two true complications. There were no cases
of re-fracture following removal of the external fixator. This review confirms
that there is a role for the use of external fixation in selected paediatric
fractures with a low complication rate.
PMID- 26435229
TI - (Un)importance of physical therapy in treatment of displaced supracondylar
humerus fractures in children.
AB - Elbow joint stiffness is a common complication following supracondylar humerus
fractures. In prospective study, dynamics of establishing a full range of motion
in the elbow joint following the treatment of supracondylar humerus fractures
were assessed, together with the effects of physical therapy on improvement in
the range of motion. Two groups of patients were observed. Physical therapy was
administered to the first group, comprised of 25 patients. The second group,
comprised of 28 patients, underwent no physical therapy. In the first few months
following treatment, the range of motion was significantly greater in the
patients who had undergone physical therapy, but after 12 months, the range of
motion was almost equal in the two groups. This study has shown that it takes
about 12 months to establish a full range of motion after the injury, and that it
is not necessary to apply physical therapy in patients with elbow fractures.
PMID- 26435230
TI - Outcome of one-stage surgical treatment of developmental dysplasia of the hip in
children from 1.5 to 6 years old. A retrospective study.
AB - This study aimed to evaluate the outcome of one-stage treatment for developmental
dysplasia of the hip (DDH) in patients after walking age. A Total of 58 children
(67 hips) were retrospectively investigated to assess the efficacy and safety of
one-stage treatment of developmental dysplasia of the hip (DDH) in children from
1.5 to 6 years of age with a mean follow-up of 4.00+/-0.43 (range 3-6.8) years.
Eleven (19%) were male, forty-seven (81%) were female. Our method consisted of
open reduction, Salter innominate osteotomy, femoral shortening and derotation.
The patients were distributed into three groups according to the age at which
they were operated: 12 (20.7%) patients with 12 hips (17.9%) were operated
between 1.5 and 2 years of age (Group I), 35 (60.3%) patients with 44 hips
(65.7%) were operated between 2 and 4 years (Group II), 11 (19%) patients with 11
hips (16.4%) were operated between 4 and 6 years (Group III). Clinical and
radiological assessment at final follow-up showed that the outcome was not
significantly different between group I and group II. But clinically, there was
significant difference between group I and group III, and also between group II
and group III. Although in the outcome of radiological assessment there was no
significant difference between group I and group II compared with group III. The
rate of avascular nerosis in group I was lower than in group II or in group III.
Children with DDH between 1.5 and 6 years of age were treated successfully with
one-stage treatment, but in our hands the best age at surgery is before 4 years
of age.
PMID- 26435231
TI - Shaft-Condylar Angle for surgical correction in neglected and displaced lateral
humeral condyle fracture in children.
AB - PURPOSE: To assess the outcome after using the Shaft-Condylar angle (SCA) as
intraoperative reference for sagittal plane correction in displaced lateral
humeral condyle fractures in children presented 3-weeks after injury. METHODS:
Ten children, with delayed presentation of a displaced lateral humeral condyle
fracture and undergoing surgery during 1999-2011, were reviewed. The goal was to
obtain a smooth articular surface with an intraoperative SCA of nearly 40 degrees
and nearest-anatomical carrying angle. They were allocated into two groups
according to the postoperative SCA [Good-reduction group (SCA=30-50 degrees ),
and Bad-reduction group (SCA<30 degrees , >50 degrees )] and the final outcomes
were then compared. RESULTS: All fractures united without avascular necrosis. The
Good-reduction group (n=7) showed a significant improvement in final range of
motion and functional outcome compared to the Bad-reduction group (n=3) (p=0.02).
However, there was no significant difference in pain, carrying angle and overall
outcome between both groups. CONCLUSION: SCA is a possible intraoperative
reference for sagittal alignment correction in late presented displaced lateral
humeral condyle fractures.
PMID- 26435232
TI - Distal Femoral Cortical Irregularity in children.
AB - Cortical abnormalities at the distal postero-medial femoral metaphysis may be
relatively common. We reviewed the plain radiographs of 197 knees in 130 children
aged between 5 and 12 years to investigate the incidence of distal femoral
cortical irregularities (DFCI) and their association with symptoms. An adductor
magnus lesion was found in 15% of cases, with an even number of irregular and
cystic lesions. A medial gastrocnemius lesion was found in 5% of cases, but no
association was found between symptoms and the lesion. Overall, lesions were
found in 25% of cases aged 5 to 9 years, but in only 13% of cases aged 12 and 13
years. Boys showed a higher incidence of both adductor magnus and medial
gastrocnemius lesions. DFCI is a benign, self-limited entity and a relatively
common radiologic finding. Regardless of whether or not symptoms are present,
imaging findings should be carefully interpreted to avoid unnecessary diagnostic
and invasive therapeutic procedures.
PMID- 26435233
TI - Isokinetic performance of hip muscles after revision total hip arthroplasty via
previous anterolateral approach.
AB - We investigated the isokinetic performance of hip muscles and clinical outcomes
after revision total hip arthroplasty (THA) via same anterolateral approach used
in primary surgery. Thirty patients who had undergone previous THA via an
anterolateral approach underwent both acetabular and femoral component revision
after aseptic loosening. The Harris Hip Score (HHS) was evaluated during a
minimum 2-year follow-up. The isokinetic muscle strength of the operated and
nonoperated hips was assessed 1 year after surgery. The HHS improved from 49.0 to
77.4. Operated and nonoperated hips exhibited similar isokinetic performance
during all measurements (flexion, extension, and abduction) (p>0.05). This
prospective study showed that the anterolateral approach preserves abductor
strength after revision THA in aseptic cases with acceptable functional and
clinical results. The main clinical relevance of this study is that the same
anterolateral approach used in previous primary THA is also safe and viable for
revision THA.
PMID- 26435234
TI - Stage-related results in treatment of hip osteonecrosis with core-decompression
and autologous mesenchymal stem cells.
AB - Our aim is to analyse the clinical outcome of a series of patients affected by
avascular necrosis of the femoral head and treated with core-decompression
technique and autologous stromal cells of the bone marrow.We enrolled in our
study 29 patients with 31 hips in total affected by avascular necrosis of the
femoral head. The clinical and radiological outcome has been assessed through
self-administered questionnaires (HHS, VAS and SF12) X-ray and Magnetic
Resonance.Of all the examined hips, 25 showed a relief of the symptoms and a
resolution of the osteonecrosis, 11 of these were at Stage I and 14 at Stage II.
The progression of the disease occurred in 6 hips (2 Stage II, 2 Stage III and 2
Stage IV). Our results show a significant decrease in joint pain level and a
success in avoiding or delaying the need of hip replacement in early stages of
osteonecrosis.
PMID- 26435235
TI - Results of Conserve Plus Hip Resurfacing: prospective clinical, radiographic and
ion study.
AB - We report the 3- to 5-year clinical, radiographic and serum ion level results of
a prospective consecutive cohort of 42 hip resurfacing arthroplasties using the
Conserve Plus implant in 39 male patients that were operated on by a single
surgeon in a community hospital. Average age was 53 years (range 34-67) at
surgery. There was one revision for a subcapital neck fracture. There were no
surgery related complications. The survival of the implant was 95%. Clinical
evaluation showed excellent results with a modified Charnley score of 17.6/18,
Harris Hip Score of 96.2/100, WOMAC of 95.1/100, Oxford Score 15.3, and UCLA
Activity Score of 8/10. Radiographic analysis showed no implant at risk, no
migration or signs of loosening, no neck narrowing and no osteolysis at final
follow-up. Average cup inclination angle was 43.5 degrees with 2 outliers (34
degrees and 57 degrees ). Ion level study showed average cobalt in serum 1.04
ug/l (range 0-4) for the whole group, 0.7 ug/l (range 0-3) in patients with
unilateral resurfacing and 2.0 ug/l (range 0-4) in patients with bilateral
resurfacing. All patients had ion levels within the safe zone. This independent
series of Conserve Plus HRA confirms good results at short- to mid-term with
excellent wear characteristics. Results for avascular necrosis were equal to
those for osteoarthritis.
PMID- 26435236
TI - Evaluation of results of conservative therapy in patients with transient
osteoporosis of hip.
AB - The present study aimed to review the general characteristics of 18 cases
diagnosed with transient osteoporosis of the hip (TOH) in our hospital within a 3
year period and to present their follow-up results after conservative treatment.
A retrospective evaluation was made of the treatment and results of follow-up of
TOH cases using physical examination and laboratory findings, hip radiographs and
magnetic resonance imaging (MRI) and Harris Hip Scores (HHS). The mean duration
of complaints of 6 females (mean age, 34.3+/-4.3 years) and 12 males (mean age,
40.7+/-10.5 years) was 6.1+/-2.7 weeks before the treatment. Three female
patients had a history of giving birth by cesarean delivery. None of the patients
had any history of trauma. MRI revealed increased intensity in T2 sequences and
decreased intensity in T1 sequences in the proximal aspect of the femur. None of
the patients had subchondral collapse or intra-articular effusion. For 3 female
patients who were breastfeeding, no medical therapy was given, but only
hyperbaric oxygen (HBO) therapy and forearm crutches. As standard management, the
other patients were prevented from weight-bearing with the use of forearm
crutches and medical therapy of diclofenac sodium, acetylsalicylic acid, and
risedronate sodium was administered and additional HBO therapy. Clinical and
radiological improvements were observed in all patients. None of the patients had
avascular necrosis (AVN) of the femoral head. There was no record of therapy
related complications. While HHS was 55.6+/-7.8 before the treatment, it
increased to 88.8+/-5.8 in the 3rd month and to 96.0+/-1.8 in the 6th month after
the treatment. This change in score over time was found to be significant.
PMID- 26435237
TI - Short-term results of surgical treatment with cephalomedullary nails for
basicervical proximal femoral fractures.
AB - The treatment of basicervical femoral fractures remains controversial. The aim of
this study was to examine the efficacy of intramedullary nail use in the surgical
treatment of basicervical fractures. In total, 28 patients with basicervical
fractures treated with proximal femoral nails were examined retrospectively.
Fracture healing was observed in all patients, who were followed at least for 6
months. While the average radiological fracture healing timing was ~10.5 (8-14)
weeks, clinical fracture healing occurred in 6 (5-9) weeks on average. Screw cut
out, avascular necrosis, femur fracture, and surgical wound infections did not
occur in any patient. Severe collapse (>10%) was not noted in any patient. The
postoperative mean Harris hip score was 81.2+/-21.3. Osteosynthesis application
with a proximal femoral nail in basicervical proximal femur fractures is a
surgical treatment that can be performed with minimally invasive techniques
without open surgery. This is a rapid, sound, and simple treatment method with
low morbidity.
PMID- 26435238
TI - Test-retest reliability of the 50-foot timed walk and 30-second chair stand test
in patients with total hip arthroplasty.
AB - The purpose was to investigate the test-retest reliability of the 50-Foot Timed
Walk (50FWT), and 30-Second Chair Stand Test (30CST) in the patients with total
hip arthroplasty (THA). The study was a test-retest study. Thirty-seven patients
with THA performed two trials for both the 30CTS and 50FWT on the same day with
one hour interval. To assess reliability, the intra-class correlation coefficient
[ICC(2,1)], standard error of measurement (SEM), the smallest real difference at
the 95% confidence level (SRD95) were calculated. The ICCs for the 50FWT and
30CTS were 0.98 and 0.94, respectively. The SEM and SRD95 for the 50FWT and 30CTS
were 0.3 and 0.8 seconds and 0.4 and 1.2 repeats, respectively. The test-retest
reliability of the tests was very high. The 50FWT and 30CST are very reliable to
measure the functional performance in patients with THA in the clinical settings.
PMID- 26435239
TI - Surgical technique for treatment of concomitant grade II MCL lesion in patients
with ACL rupture.
AB - Combined lesions of anterior cruciate ligament (ACL) and medial collateral
ligament (MCL) are frequent in athletes. While surgical treatment of ACL injury
is mandatory treatment regime of concomitant grade II MCL lesions remains unclear
with tendency to surgical intervention. Standardized surgical technique is
lacking. Present study wants to introduce surgical technique for treatment of
concomitant grade II MCL lesion and report short term outcome results. 5 Patients
with acute ACL rupture and grade II MCL-lesion were included. All patients
received surgical treatment of concomitant MCL lesion by distinct surgical
technique and ACL reconstruction. We evaluated valgus instability, anterior
instability and range of motion (ROM) according to international knee
documentation commitee (IKDC) and Lysholm-Score both preoperative and after 6, 16
weeks and 9 months postoperative. All Patients showed excellent clinical results
at final follow-up. Valgus and anterior stability could be restored in all
patients. 1 patient (20%) lost 15 degrees in flexion of ROM at final follow up.
However in all 5 patients (100%) the findings were graded as normal or nearly nor
mal according to IKDC knee examination form. Lysholm-Score averaged 94,6.
Therefore presented surgical technique improved both, valgus and anterior
stability, and led to excellent short term results at final follow up.
PMID- 26435240
TI - Early follow-up after primary total knee and total hip arthroplasty with rapid
recovery : Focus groups.
AB - Rapid recovery protocols reduce the length of hospital stay after Total Knee
Arthroplasty (TKA) and Total Hip Arthroplasty (THA). However, little is known
about the early postoperative phase. The purpose of this study was to examine
which problems patients encountered during the first six weeks after primary TKA
or THA surgery with rapid recovery. We invited twenty patients for a focus group
meeting which discussed various subjects regarding the first six weeks after
hospital discharge. The focus group meetings were analysed qualitatively.
Patients were mostly satisfied by the short length of hospital stay. Patients who
lived alone needs more care and would like to stay longer in the hospital. After
THA surgery all patients complained of inability to sleep. More patients
experienced pain after TKA surgery compared to THA surgery. All patients had
various experiences regarding physical therapy therefore an evidence based
rehabilitation protocol might be needed.
PMID- 26435241
TI - Comparative study of innovative postoperative wound dressings after total knee
arthroplasty.
AB - PURPOSE: Postoperative wound complications, especially surgical site infections,
influence the outcome after total knee arthroplasty. The purpose of our study was
to compare four different wound dressings. Following research questions were
asked : (1) Which dressing is associated with least wound complications? (2)
Which dressing application is the cheapest? (3) Which dressing is most
comfortable for the patient? METHODS: 111 patients undergoing a total knee
arthroplasty were randomized in 4 groups. Each group received a different
dressing with its specific wound management protocol : (1) Zetuvit(r) with
Cosmopor E(r), (2) Zetuvit(r) with Opsite Post-Op Visible(r), (3) Aquacel
Surgical(r) and (4) Mepilex Border(r). Follow-up evaluations were performed on
the fifth postoperative day and included assessment of the wound, status of the
wound dressing and the patient's own judgment. Cumulative costs were calculated.
RESULTS: Clinically Mepilex Border(r), a silicone dressing, scored the best. No
wound complications were seen in this group. The mean number of dressing renewals
was 1.9 for the standard dressing which was significantly higher (p<.0001)
compared to the other dressings. Opsite Post-op Visible(r) was the cheapest
dressing. Mepilex Border(r) had the best scores for pain, freedom of movement and
general comfort. CONCLUSIONS: Mepilex Border(r) is the most skin-friendly
dressing. The number of dressing renewals is a defining factor to calculate the
costs. Mepilex Border(r) appeared to be the best dressing to use after a total
knee arthroplasty.
PMID- 26435242
TI - The indirect cost of Patient-Specific Instruments.
AB - PURPOSE: To calculate the indirect costs of Patient Specific Instruments (PSI)
based on an opportunity cost, cost of efforts and a supply chain cost model to
compare PSI for value with conventional total knee arthroplasty (TKA). METHODS:
In 81 patients the total (direct+indirect) cost of PSI-assisted TKA was compared
with conventional TKA. Surgical times and coronal mechanical alignment were
measured to evaluate the effectiveness of the PSI system. RESULTS: Indirect costs
(459 euro) make up 40% of the total cost that can run up to 1142 euro for a
patient operated with PSI guides. No difference in surgical times or coronal
alignment was observed in between both groups. CONCLUSION: Considering the total
cost of PSI no value was found for the use of PSI in primary TKA as measured by
surgical times or for obtaining a neutral mechanical axis in the coronal plane.
PMID- 26435243
TI - Current opinions about coronal plane alignment in total knee arthroplasty: A
survey article.
AB - PURPOSE: To survey an audience of international knee surgeons about their current
opinions on the analysis of coronal knee alignment and their objectives for
postoperative alignment in total knee arthroplasty. METHODS: Survey of 300
surgeons from 32 different countries with an audience response system allowing
three possible answers being either a positive or negative answer or an
abstention. RESULTS: Surveyed surgeons perform rarely preoperative and
postoperative full leg radiographs and evaluate radiological outcomes more with
short films. The main trend in this survey was towards neutral mechanical
alignment, however varus alignment is acceptable in constitutional varus
patients. This residual varus should be obtained through a femoral varus cut
rather than a tibial varus cut. The valgus knee can remain in slight valgus but
most of the correction will be performed at the femoral level. The main objective
of postoperative alignment in TKA is a joint line parallel to the floor and a
central load-bearing axis through the middle of the arthroplasty. Surgeons prefer
unicompartmental arthroplasty more for themselves than for their patients in case
of medial bone on bone arthritis. CONCLUSIONS: Neutral mechanical axis with a
joint line parallel to the floor and a centrally running load bearing axis
remains the central scope of the surveyed surgeons. Because of the literature on
residual varus it becomes more acceptable for the orthopaedic community to accept
this type of outlier before aiming at a surgical correction.
PMID- 26435244
TI - Is systematic long-term sonographic follow-up after arthroscopic rotator cuff
repair useful in asymptomatic patients?
AB - OBJECTIVE: To establish whether ultrasonographic (US) appearance is correlated to
functional outcome in asymptomatic patients 12 months after rotator cuff repair.
MATERIAL AND METHODS: 26 asymptomatic patients at twelve months after
arthroscopic cuff repair and 26 controls were retrospectively included. A
clinical score (Constant's Shoulder Score, CSS) was compared with a US score (the
modified Sugaya Score, mSS). The minimal thickness of the anterior and posterior
parts of the cuff was also measured. RESULTS: CSS improved significantly from
preoperatively to postoperatively (mean increased from 41 to 82.6, p<.001).
Correlation between the postoperative CSS and the minimal thickness of the cuff
at its anterior and posterior part (p=0.55 and p=0.13) was not significant. There
was also no significant correlation between the postoperative CSS and mSS
(p=0.34). CONCLUSION: The sonographic appearance of the cuff repair is not
correlated to the functional outcome at 12 months after arthroscopic surgery in
asymptomatic patients.
PMID- 26435245
TI - Passive mobilization after arthroscopic rotator cuff repair is not detrimental in
the early postoperative period.
AB - This prospective randomized study compares the clinical results of immediate
passive mobilization versus delayed mobilization in the rehabilitation of rotator
cuff repair during the early postoperative period. The mobilization group (79
patients) received immediate daily passive mobilization. The immobilization group
(51 patients) was immobilized for 4 weeks until physiotherapy was started.
Passive range of motion was noted preoperatively, at 6 weeks and 4 months.
Strength was measured preoperatively and at 4 months. Constant-Murley, Simple
Shoulder Test, SPADI and UCLA scores were noted at baseline and at 4 months.
Ultrasonography was performed at 6 weeks to exclude early failures of repair. We
noted no significant difference between the two groups regarding range of motion
at 6 weeks and range of motion, strength and functional outcome scores at 4
months. Ultrasound didn't show a difference in healing at 6 w in either of both
groups. Both rehabilitation protocols seem applicable as well as safe in the
early post-operative phase.
PMID- 26435246
TI - Fracture-dislocation of the humeral condyles in adults: results of surgical
treatment.
AB - Fracture-dislocation of the humeral condyle is exceptional in adults. The purpose
was to analyze the results of surgical treatment by open reduction and internal
fixation without ligamentous repair. There were six men with an average age of 31
years. According to the AO classification, five fractures were classified as AO
type B1 and one as B2. Dislocation was reduced in emergency before
osteosynthesis. Postoperatively, the joint was held immobile with a brace for
25.40 days. Five patients were reviewed after a mean follow-up of 52.96 months.
The median arc of flexion/extension was 104.80 degrees and 157.8 degrees for
pronation-supination. All elbows were stable and all fractures were consolidated.
Two elbows were painful. The results were satisfactory in five patients. The
elbow stability can be ensured only by the synthesis of bone structures. Surgical
treatment should restore exact anatomy between the condyle and trochlea. This
protocol may provide a joint stability and satisfactory results.
PMID- 26435247
TI - Operative management of humeral nonunions. Factors that influence the outcome.
AB - The purpose of this study is to present the outcome of surgically treated humeral
nonunions and find factors that affect the outcome. Forty-two patients with
humeral nonunions (30 shaft, 7 proximal and 5 distal) were reviewed in a
prospective manner. Treatment was based on a specific algorithm. Demographics,
time to union, range of motion, functional outcome and complications were
recorded and analysed. RESULTS: Mean follow-up was 78 months and mean time to
union was 4.3 months. Infection was associated with delayed union of the
pseudarthrosis, while range of motion was negatively affected by the location
(proximal) and the AO type of the initial fracture. Complication rate was 17%.
CONCLUSION: The surgical management of humeral nonunions yields a favourable
outcome with reduced rate of complications. Infection prolonged healing time,
while proximal location of the nonunion and the type B or C fracture according to
AO/OTA classification adversely affected range of motion.
PMID- 26435248
TI - Correlation between dorsovolar translation and rotation of the radius on the
distal radioulnar joint during supination and pronation of forearm.
AB - This study aimed to describe the patterns of movements about radius and ulna in
individual degrees of forearm rotation. And, we also determined the effect of
forearm rotation on translation and rotation of the radius with reference to the
ulna, and to measure the relationship between forearm rotation, translation and
rotation of the radius. Computed tomography of multiple, individual forearm
positions, from 90 degrees pronation to 90 degrees supination, was conducted in
26 healthy volunteers (mean age, 43.9 years) to measure dorsovolar translation
and rotation of the radius in the DRUJ in each forearm position. The mean
dorsovolar translations were within 1.99 mm at 90 degrees pronation to -2.03 mm
at 90 degrees supination. The rotations of the radius were 71.20 degrees at 90
degrees pronation and -46.63 degrees at 90 degrees supination. There were
strong correlations between degrees of forearm rotation and dorsovolar
translation (r=0.861, p<0.001) and rotation of the radius (r=0.960, p<0.001),
suggesting that the DRUJ, carpal joints, and rotatory laxity of the carpal
ligament, especially in supination, contribute to forearm supination and
pronation. These findings provide an understanding of wrist kinematics, are may
be useful in reconstructive wrist surgery to achieve normal range of motion, and
are may be helpful for the design of DRUJ reconstruction using prostheses.
PMID- 26435249
TI - Management of infectious fractures with "Non-Contact Plate" (NCP) method.
AB - The aim of this study was to evaluate the outcomes of internal fixation with Non
Contact Plating (NCP) after deep infection caused by previous surgeries of the
tibia or femur fractures. The study included 15 patients (4 female and 11 male).
The mean age patients was 36.6 years (range, 21-64 years). There were 6 femur and
9 tibia fractures. The mean follow-up period was 25.7 months (range, 15-45
months). The study comprised 11 open and 4 closed fractures. External fixator was
used in 3, plate in 4, and intramedullary nail in 8 patients for index surgery.
Deep infection was diagnosed via clinical findings, laboratory parameters, and
microbiological evaulation. Deep infection was diagnosed within a mean period of
5.5 weeks (range, 2-10 weeks). The infecting organism was methicillin-resistant
staphylococcus aureus (MRSA) in 5, methicillin-sensitive staphylococcus aureus
(MSSA) in 6, pseudomonas auroginosa in 2, and enterobacteriacea in 2 patients.
Union achieved in all patients. Mean time to union was 17 (range, 11-38) weeks.
Delayed union was observed in 3 patients who required additional surgeries. Of
these one patient developed osteomyelitis. The NCP is an effective alternative
method in the treatment of deep infection encountered after internal or external
fixation for the tibia, or femur fractures.
PMID- 26435250
TI - Oncological approach with antihelminthic chemotherapy and wide resection in the
treatment of musculoskeletal hydatidosis. A review of 10 cases with mean follow
up of 64 months.
AB - The objective of this retrospective study was to evaluate clinical outcomes,
local recurrence and complication rates of antihelminthic chemotherapy and wide
resection in patients with muscle or bone hydatidosis. The authors treated 10
patients (6 females, 4 males) between 2004 and 2012: 8 with muscle and 2 with
bone hydatidosis. The mean age at surgery was 42.5 years (range, 11-66 years).
All patients were treated with wide resection and pre- and postoperative
chemotherapy with albendazole. The mean follow-up was 64 months (range, 28-120
months). All patients achieved satisfactory clinical outcomes. There were no
local recurrences. Surgical complications were seen in 3 patients (30%) : one
superficial infection, one deep infection, and one hematoma. Two (20%) required
additional surgery. An aggressive oncological approach, consisting of
antihelminthic chemotherapy and wide resection, can provide favorable clinical
outcomes and prevent local recurrence in patients with musculoskeletal
hydatidosis. Potential complications of aggressive surgery should be preferred to
potential morbidity of local and systemic dissemination.
PMID- 26435251
TI - Analysis of sagittal balance using spinopelvic parameters in ankylosing
spondylitis patients treated with vertebral column decancellation surgery.
AB - This study was designed to explore the change of spinopelvic parameters after
vertebral column decancellation (VCD) for the management of thoracolumbar
kyphosis secondary to ankylosing spondylitis (AS). Forty-two AS patients
including thirty-six males and six females with thoracolumbar kyphosis, who
underwent VCD from April 2005 to June 2012 in our hospital, were retrospectively
reviewed. A series of spinopelvic parameters including thoracic kyphosis (TK),
lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT)
and sagittal vertical axis (SVA) measured on preoperative and postoperative free
standing radiographs were obtained and analyzed. Also clinical assessments were
performed with the Oswestry disability index (ODI) and the Bath Ankylosing
Spondylitis Activity and Function Index (BASDAI and BASFI) so as to seek
correlations between radiological parameters and symptoms. Except for pelvic
incidence (PI), significant difference was found in all radiological spinopelvic
parameters between the preoperative and follow-up values. Furthermore, there was
significant improvement in the clinical assessment parameters ODI, BASDAI and
BASFI, which all correlated significantly with the postoperative pelvic tilt
(PT). The results of this study show that posterior VCD is an effective option to
manage sagittal imbalance in AS. In the current series, patients improving LL and
PT were found to achieve good clinical outcomes. Overall, our findings show that
it is important to quantify sagittal spinopelvic parameters and promote sagittal
balance in the surgery for AS.
PMID- 26435252
TI - Long-term follow-up of the anterior lumbar interbody fusion procedure.
AB - PURPOSE: To evaluate the long-term clinical results and the effectiveness of the
anterior lumbar interbody fusion procedure. METHODS: Between 1999 and 2005, 60
ALIFs were performed in 59 patients. Mean age was 41.1 years. Clinically,
patients were evaluated at a mean follow-up of 9.5 years using the Visual
Analogue Scale grading scale, the Oswestry Disability score and the SF-36
questionnaire. RESULTS: Preoperative and postoperative clinical evaluation scores
of 38 patients were available. Nineteen patients were lost to follow-up, and 2
patients died during the follow-up. The fusion rate was 84%. Mean preoperative
VAS-score for back pain was 6.69 (+/-2.15) ; in the long term, the mean VAS-score
was 4.95 (+/-2.95), which was a significant improvement. (p<0.01). The
postoperative ODI-score was 36.11 (+/-22.32), while the preoperative ODI-score
was 59.31 (+/-17.16), which demonstrates a significant improvement. According to
the SF-36, mild to good results were observed. CONCLUSIONS: The ALIF procedure
can offer significant pain relief and improved function if a strict indication
policy is followed.
PMID- 26435253
TI - Neglected Achilles Tendon Rupture Treated with Flexor Hallucis Longus transfer
with two turndown gastrocnemius fascia flap and reinforced with plantaris tendon.
AB - Neglected Achilles Tendon Ruptures are commonly seen by orthopaedic surgeons. In
cases resistant to conservative treatment, a variety of surgical procedures have
been utilized in the past. The senior -surgeon at our institution has utilized a
technique -employing two turndown fascia flaps fashioned from the proximal
Achilles tendon augmented by a tenomyodesis of the flexor hallucis longus and
plantaris tendon. The purpose of this study was to assess the clinical outcome of
all patients who underwent this procedure. The medical records of 10 cases that
underwent this procedure were retrospectively reviewed. We completed data
collection sets using the American Orthopaedic Foot and Ankle Society ankle-hind
foot scores, isokinetic evaluation, and postoperative magnetic resonance imaging
(MRI) at 1 year of follow-up. The mean American Orthopaedic Foot and Ankle
Society ankle-hind foot scores improved from 64.4+/-3.54. Isokinetic testing at
30o/sec and 120o/sec revealed an mean deficits of 24.5%, respectively, in the
plantar flexion peak torque of the involved ankle than non-involved ankle. The
flexor hallucis longus tendon, gastrocnemius fascia flap and plantaris were well
integrated into the Achilles tendon forming a homogenous tendon, which was
confirmed in MRI. Our subjective and objective data indicate that the
reconstructive technique using flexor hallucis longus transfer with two turndown
gastrocnemius fascia flaps and plantaris tendon is a good option for repairing
large gap defect of Achilles tendon.
PMID- 26435254
TI - Habitual suppression relates to difficulty in regulating emotion with cognitive
reappraisal.
AB - One common strategy to cope with the difficulties of daily life is suppression.
Habitual users of suppression tend to suppress their feelings rather than
expressing them. Although this strategy may reduce outward response to emotion,
it is not thought to lessen induced negative affect. Moreover, it remains unclear
whether people with high suppression scores can reduce negative affect through
cognitive reappraisal. In the present study, twenty-nine healthy participants
differing in suppression scores were directed to reappraise aversive stimuli
during functional magnetic resonance imaging (fMRI). Results showed that higher
suppression scores correlated with decreased response of dorsomedial prefrontal
cortex (dmPFC) during cognitive reappraisal. Further, high suppression scores
related to enhanced negative affect to stimuli with greater negative affect
correlating with decreased dmPFC response during cognitive reappraisal. This
study suggests that people with high suppression scores experience difficulty in
reducing negative affect through cognitive reappraisal and implicates
neurobiological processes that may underlie this difficulty.
PMID- 26435255
TI - The "Cryptic" Escherichia.
AB - In 2009, five monophyletic Escherichia clades were described and referred to as
"cryptic" based on the inability to distinguish them from representative E. coli
isolates using diagnostic biochemical reactions. Since this original publication,
a number of studies have explored the genomic, transcriptomic, and phenotypic
diversity of cryptic clade isolates to better understand their phylogenetic,
physiological, and ecological distinctiveness with respect to previously named
Escherichia species. This chapter reviews the original discovery of the cryptic
clades, discusses available evidence that some are environmentally adapted, and
evaluates current support for taxonomic designations of these microorganisms. The
importance of these clades to clinical research, epidemiology, population
genetics, and microbial speciation is also discussed.
PMID- 26435256
TI - DNA Topoisomerases.
AB - DNA topoisomerases are enzymes that control the topology of DNA in all cells.
There are two types, I and II, classified according to whether they make
transient single- or double-stranded breaks in DNA. Their reactions generally
involve the passage of a single- or double-strand segment of DNA through this
transient break, stabilized by DNA-protein covalent bonds. All topoisomerases can
relax DNA, but DNA gyrase, present in all bacteria, can also introduce supercoils
into DNA. Because of their essentiality in all cells and the fact that their
reactions proceed via DNA breaks, topoisomerases have become important drug
targets; the bacterial enzymes are key targets for antibacterial agents. This
article discusses the structure and mechanism of topoisomerases and their roles
in the bacterial cell. Targeting of the bacterial topoisomerases by inhibitors,
including antibiotics in clinical use, is also discussed.
PMID- 26435257
TI - Biosynthesis and Insertion of the Molybdenum Cofactor.
AB - The transition element molybdenum (Mo) is of primordial importance for biological
systems, because it is required by enzymes catalyzing key reactions in the global
carbon, sulfur, and nitrogen metabolism. To gain biological activity, Mo has to
be complexed by a special cofactor. With the exception of bacterial nitrogenase,
all Mo-dependent enzymes contain a unique pyranopterin-based cofactor
coordinating a Mo atom at their catalytic site. Various types of reactions are
catalyzed by Mo-enzymes in prokaryotes including oxygen atom transfer, sulfur or
proton transfer, hydroxylation, or even nonredox reactions. Mo-enzymes are
widespread in prokaryotes and many of them were likely present in the Last
Universal Common Ancestor. To date, more than 50--mostly bacterial--Mo-enzymes
are described in nature. In a few eubacteria and in many archaea, Mo is replaced
by tungsten bound to the same unique pyranopterin. How Mo-cofactor is synthesized
in bacteria is reviewed as well as the way until its insertion into apo-Mo
enzymes.
PMID- 26435259
TI - Acute effects of active gaming on ad libitum energy intake and appetite
sensations of 8-11-year-old boys.
AB - The present study examined the acute effects of active gaming on energy intake
(EI) and appetite responses in 8-11-year-old boys in a school-based setting.
Using a randomised cross-over design, twenty-one boys completed four individual
90-min gaming bouts, each separated by 1 week. The gaming bouts were (1) seated
gaming, no food or drink; (2) active gaming, no food or drink; (3) seated gaming
with food and drink offered ad libitum; and (4) active gaming with food and drink
offered ad libitum. In the two gaming bouts during which foods and drinks were
offered, EI was measured. Appetite sensations - hunger, prospective food
consumption and fullness - were recorded using visual analogue scales during all
gaming bouts at 30-min intervals and at two 15-min intervals post gaming. In the
two bouts with food and drink, no significant differences were found in acute EI
(MJ) (P=0.238). Significant differences were detected in appetite sensations for
hunger, prospective food consumption and fullness between the four gaming bouts
at various time points. The relative EI calculated for the two gaming bouts with
food and drink (active gaming 1.42 (sem 0.28) MJ; seated gaming 2.12 (sem 0.25)
MJ) was not statistically different. Acute EI in response to active gaming was no
different from seated gaming, and appetite sensations were influenced by whether
food was made available during the 90-min gaming bouts.
PMID- 26435258
TI - Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene
expression among women with cervical abnormalities and cancer.
AB - Cervical cancer is caused by infection with high risk human papillomavirus (HR
HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in
chronic inflammation, may modulate cervical cancer risk among HPV infected women.
The aim of the study was to measure and correlate plasma nitrite/nitrate levels
with tissue specific expression of iNOS mRNA among women with different grades of
cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were
collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and
invasive cancer) and 35 women without cervical abnormalities. Inducible nitric
oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the
same study subjects were measured. Single nucleotide polymorphism (SNP) analysis
was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the
iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels
were compared across disease stage using linear and logistic regression analysis.
Compared to normal controls, women diagnosed with HSIL or invasive cancer had a
significantly higher concentration of plasma nitrite/nitrate and a higher median
fold-change in iNOS mRNA gene expression. Genotyping of the promoter region
showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G
(rs2779249) and a novel variant -1153T > A. These variants were associated with
increased levels of plasma nitrite/nitrate across all disease stages. The higher
expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous
lesions suggests a role for nitric oxide in the natural history of cervical
cancer.
PMID- 26435260
TI - Expression and regulation of tissue inhibitors of metalloproteinases (TIMP1 and
TIMP3) in goat oviduct.
AB - Tissue inhibitors of metalloproteinases (TIMPs) are associated with several
reproductive processes, such as mammalian follicular growth, ovulation, CL
formation, and embryonic development. However, the expression and function of
TIMPs in goat oviducts remain unclear. This work aimed to identify TIMP1 and
TIMP3 expression in the goat oviduct during the estrous cycle via
immunohistochemistry, real-time polymerase chain reaction (PCR), and functional
studies in cultured goat oviductal epithelial cells. Real-time PCR results
demonstrated that TIMP1 and TIMP3 messenger RNAs were expressed in all goat
oviductal regions at all stages of the estrous cycle. TIMP1 and TIMP3 proteins
were also highly expressed in oviductal epithelial cells with very limited
expression in other cell types. Oviductal epithelial cells were treated in vitro
with various estradiol concentrations (1-100 nM) for 24 hours. The findings
showed that TIMP1 expression increased up to 20 nM but then gradually decreased,
whereas no significant effects existed among TIMP3 messenger RNA levels. Time
course studies indicated that estradiol significantly increased TIMP1 expression
in a time-dependent manner from 8 hours to 24 hours. By contrast, TIMP3
expression was transiently induced in oviductal epithelial cells at 2 and 4 hours
after estradiol treatment. Furthermore, treatment with TIMP1 functionally
increased the viability of cultured oviductal epithelial cells. Overall, the
results suggested that the differential regulation and function between TIMP1 and
TIMP3 might be associated with their unique roles in fertilization and early
embryonic development.
PMID- 26435261
TI - Mechanism for greater frequency of contralateral than ipsilateral relationships
between corpus luteum and ovulatory follicle for wave 3 in heifers.
AB - During the last wave of the interovulatory interval (IOI), the permutations of
the relationship between the ovulatory follicle and the CL (ipsilateral vs.
contralateral) and the number of follicular waves (two vs. three) per IOI differ
in frequency of occurrence as follows: ipsilateral relationship and two waves
(34%), contralateral relationship and two waves (34%), ipsilateral relationship
and three waves (8%), and contralateral relationship and three waves (24%).
Deviation or the continuation in growth rate of the future ovulatory follicle and
a decrease in growth rate of the future subordinate follicles begin well before
luteolysis in two-wave IOIs and during luteolysis in three-wave IOIs. The largest
follicle decreases in diameter and loses its dominant status before completion of
deviation when it is ipsilateral and adjacent to the regressing CL during wave 3.
Dominant status switches from the largest follicle in the ipsilateral ovary to
the next-largest follicle which may be in either ovary. Switching accounts for
the greater frequency of a contralateral follicle-CL relationship than for
ipsilateral follicle-CL relationship during the ovulatory wave in three-wave
IOIs. It is proposed that the phenomenon results from commonality in
angioarchitecture so that the decrease in blood flow to the regressing CL is
associated with a decrease in blood flow to adjacent follicles.
PMID- 26435262
TI - Contribution of semen trait selection, artificial insemination technique, and
semen dose to the profitability of pig production systems: A simulation study.
AB - The economic impact of selection for semen traits on pig production systems and
potential interaction with artificial insemination (AI) technique and semen dose
remains partially understood. The objectives of this study were to compare the
financial indicators (gross return, net profit, cost) in a three-tier pig
production system under one of two selection strategies: a traditional strategy
including nine paternal and maternal traits (S9) and an advanced strategy that
adds four semen traits (S13). Maternal traits included the number of pigs born
alive, litter birth weight, adjusted 21-day litter weight, and the number of pigs
at 21 days, and paternal traits included days to 113.5 kg, back fat, average
daily gain, feed efficiency, and carcass lean percentage. The four semen traits
included volume, concentration, progressive motility of spermatozoa, and abnormal
spermatozoa. Simultaneously, the impact of two AI techniques and a range of fresh
refrigerated semen doses including cervical AI with 3 * 10(9) (CAI3) and 2 *
10(9) (CAI2) sperm cells/dose, and intrauterine AI with 1.5 * 10(9) (IUI1.5),
0.75 * 10(9) (IUI0.75), and 0.5 * 10(9) (IUI0.5) sperm cells/dose were evaluated.
These factors were also evaluated using a range of farrowing rates (60%-90%),
litter sizes (8-14 live-born pigs), and a selected semen collection frequency.
The financial impact of the factors was assessed through simulation of a three
way crossbreeding system (maternal nucleus lines A and B and paternal nucleus
line C) using ZPLAN. The highest return on investment (profit/cost) of boars was
observed at 2.33 collections/wk (three periods of 24 hours between collections).
Under this schedule, a significant (P < 0.0001) interaction between the selection
strategy and the AI technique-dose combination was identified for the gross
return; meanwhile, significant (P < 0.0001) additive effects of the selection
strategy and AI technique-dose combination were observed for the net profit. The
highest gross return was obtained under S13 with IUI0.75 and IUI0.5. The net
profit of S13 was 34.37% higher than the traditional S9 (P < 0.0001). The net
profit favored IUI0.5 with relative differences of 4.13%, 2.41%, 1.72%, and 0.43%
compared to CAI3, CAI2, IUI1.5, and IUI0.75, respectively. The advanced selection
strategy proposed including four semen traits is recommended on the basis of the
higher profitability relative to the traditional strategy.
PMID- 26435263
TI - Analysis of sacro-iliac joint screw fixation: does quality of reduction and screw
orientation influence joint stability? A biomechanical study.
AB - INTRODUCTION: Treatment of posterior pelvic ring injuries is frequently
associated with pain or/and high mortality rates. Percutaneous sacro-iliac (SI)
screw fixation has proved to be one of the methods of choice, providing minimal
operative time, blood loss and wound-related morbidity. However, fixation
failures due to secondary fracture dislocation or screw backing out have been
reported. There is a little knowledge regarding the impact of varying screw
orientation and quality of reduction on the fixation strength. PURPOSE: The
purpose of the present study was biomechanical investigation of joint stability
after SI screw fixation and its dependence on quality of reduction and screw
orientation. METHODS: Thirty-two artificial hemi-pelvices were assigned to four
study groups and simulated SI dislocations were fixed with two SI screws in
oblique or transverse screw orientation and anatomical or non-anatomical
reduction in group A (oblique/anatomical), B (transverse/anatomical), C
(oblique/non-anatomical) and D (transverse/non-anatomical). Mechanical testing
was performed under progressively increasing cyclic axial loading until fixation
failure. SI joint movements were captured via optical motion tracking. Fixation
performance was statistically evaluated at a level of significance p = 0.05.
RESULTS: The highest cycles to failure were observed in group A (14038 +/- 1057),
followed by B (13909 +/- 1217), D (6936 +/- 1654) and C (6706 +/- 1295). Groups A
and B revealed significantly longer endurance than C and D (p <= 0.01).
CONCLUSIONS: Different screw orientations in the presented model do not influence
substantially SI joint stability. However, anatomical reduction is not only
mandatory to restore a malalignment, but also to increase the SI screw fixation
strength and prevent fixation failures.
PMID- 26435265
TI - Dynamical heterogeneities and defects in two-dimensional soft colloidal crystals.
AB - In this paper we study a two-dimensional system of charged colloidal particles
using Brownian dynamics simulations. We determine the phase diagram and
investigate the dynamics of this system in the density regime where hexatic and
solid phases are stable. We find that the dynamics in these phases is
heterogeneous by means of the spontaneous formation and diffusion of highly
mobile defects. We identify two key mechanisms associated with the areas of high
mobility. The first mechanism involves the highly cooperative motion of a closed
loop of particles which shift coherently along the loop until each particle has
replaced the position of its predecessor in the chain. The second mechanism
involves the spontaneous creation of vacancy-interstitial pairs which diffuse
within the hexatic and solid phases. We further explore quantitatively the
properties of the open-ended and closed rearrangement strings and find that in
the crystal phase the string-size distribution can be approximately matched with
a simple, random walk description of vacancies and interstitials on a lattice.
PMID- 26435264
TI - Complications and revisions after semi-constrained total elbow arthroplasty: a
mono-centre analysis of one hundred cases.
AB - BACKGROUND: The complication rate after total elbow arthroplasties is higher than
for other arthroplasties. PURPOSE: The purpose of this study was to evaluate the
complications and revision rate after 100 semi-constrained total elbow
arthroplasties from various types of aetiologies performed in our university
hospital. METHODS: One hundred linked semiconstrained total elbow arthroplasties
were performed and were reviewed with 24-months minimum follow-up. Indications
were rheumatoid arthritis (45), trauma (33), revisions (16) and others (6).
RESULTS: At five years average follow-up (range, 2-11), the complication rate was
37 %. Most frequent complications were ulnar nerve involvement (9 %) and triceps
insufficiency (7 %). Five implants were aseptically loosed. The infection rate
was 4 % with loosening of the implant in two. Four fractures were observed,
including three at the ulna and one at the humerus proximal or distal to the
stem. The radial nerve was injured in two cases. Failure of the locking system of
the prosthesis was noted in one case and a fracture of the ulnar component was
found in another patient. A revision surgery was performed in 13 cases (13 %). At
follow-up 94 prostheses were still in place and the survival rate was 98 % at
five years and 86 % at ten years. CONCLUSION: Total elbow arthroplasty remains a
difficult procedure with sometimes a high rate of complications necessitating
revision procedures. Selection of the patients, a rigorous surgical technique,
and a systematic follow-up are prerequisite to limit this incidence. TYPE OF
STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 26435266
TI - Excellent optical and interfacial performance of a PEDOT-b-PEG block copolymer
counter electrode for polymer electrolyte-based solid-state dye-sensitized solar
cells.
AB - A poly(3,4-ethylenedioxythiophene)-b-poly(ethylene glycol) (PEDOT-b-PEG) block
copolymer doped with perchlorate on FTO shows excellent optical and interfacial
performance as a counter electrode (CE), such as low charge transfer resistance
and low reflectivity for polymer electrolyte-based solid-state dye-sensitized
solar cells (DSCs), resulting in 8.45% energy conversion efficiency, greater than
the common Pt CE, via a facile room-temperature process.
PMID- 26435267
TI - Ultrasonically treated liquid interfaces for progress in cleaning and separation
processes.
AB - Ultrasound and acoustic cavitation enable ergonomic and eco-friendly treatment of
complex liquids with outstanding performance in cleaning, separation and
recycling of resources. A key element of ultrasonic-based technology is the high
speed of mixing by streams, flows and jets (or shock waves), which is accompanied
by sonochemical reactions. Mass transfer across the phase boundary with a great
variety of catalytic processes is substantially enhanced through acoustic
emulsification. Encapsulation, separation and recovery of liquids are fast with
high production yield if applied by ultrasound. Here we discuss the state of
knowledge of these processes by ultrasound and acoustic cavitation from a
perspective of a physico-chemical model in order to predict and control the
outcome. We focus on the physical interpretation and quantification of ultrasonic
parameters and properties of liquids to understand the chemistry of liquid/liquid
interfaces in acoustic fields. The roles of thermodynamic enthalpy and entropy
(incl. Laplace and osmotic pressure) in the context of sonochemical reactions
(separation, catalysis, degradation, cross-linking, ion exchange and phase
transfer) are outlined. The synergy of ultrasound and electric fields or
continuous flow chemistry for cleaning and separation via emulsification is
highlighted by specific strategies involving polymers and ultrasonic membranes.
PMID- 26435269
TI - Model free audit methodology for bias evaluation of tumour progression in
oncology.
AB - Many oncology studies incorporate a blinded independent central review (BICR) to
make an assessment of the integrity of the primary endpoint, progression free
survival. Recently, it has been suggested that, in order to assess the potential
for bias amongst investigators, a BICR amongst only a sample of patients could be
performed; if evidence of bias is detected, according to a predefined threshold,
the BICR is then assessed in all patients, otherwise, it is concluded that the
sample was sufficient to rule out meaningful levels of bias. In this paper, we
present an approach that adapts a method originally created for defining futility
bounds in group sequential designs. The hazard ratio ratio, the ratio of the
hazard ratio (HR) for the treatment effect estimated from the BICR to the
corresponding HR for the investigator assessments, is used as the metric to
define bias. The approach is simple to implement and ensures a high probability
that a substantial true bias will be detected. In the absence of bias, there is a
high probability of accepting the accuracy of local evaluations based on the
sample, in which case an expensive BICR of all patients is avoided. The
properties of the approach are demonstrated by retrospective application to a
completed Phase III trial in colorectal cancer. The same approach could easily be
adapted for other disease settings, and for test statistics other than the hazard
ratio.
PMID- 26435268
TI - Sleep Disturbance and Expressive Language Development in Preschool-Age Children
With Down Syndrome.
AB - Recent evidence has suggested that sleep may facilitate language learning. This
study examined variation in language ability in 29 toddlers with Down syndrome
(DS) in relation to levels of sleep disruption. Toddlers with DS and poor sleep
(66%, n = 19) showed greater deficits on parent-reported and objective measures
of language, including vocabulary and syntax. Correlations between sleep and
language were found in groups with equivalent medical and social backgrounds and
after control for relevant behavioral comorbidities, including autism symptoms.
These results emphasize the important role of quality sleep in all children's
expressive language development, and may help increase our understanding of the
etiology of language deficits in developmental disorders, potentially leading to
new treatment approaches.
PMID- 26435270
TI - Transient and 2-Dimensional Shear-Wave Elastography Provide Comparable Assessment
of Alcoholic Liver Fibrosis and Cirrhosis.
AB - BACKGROUND & AIMS: Alcohol abuse causes half of all deaths from cirrhosis in the
West, but few tools are available for noninvasive diagnosis of alcoholic liver
disease. We evaluated 2 elastography techniques for diagnosis of alcoholic
fibrosis and cirrhosis; liver biopsy with Ishak score and collagen-proportionate
area were used as reference. METHODS: We performed a prospective study of 199
consecutive patients with ongoing or prior alcohol abuse, but without known liver
disease. One group of patients had a high pretest probability of cirrhosis
because they were identified at hospital liver clinics (in Southern Denmark). The
second, lower-risk group, was recruited from municipal alcohol rehabilitation
centers and the Danish national public health portal. All subjects underwent same
day transient elastography (FibroScan), 2-dimensional shear wave elastography
(Supersonic Aixplorer), and liver biopsy after an overnight fast. RESULTS:
Transient elastography and 2-dimensional shear wave elastography identified
subjects in each group with significant fibrosis (Ishak score >=3) and cirrhosis
(Ishak score >=5) with high accuracy (area under the curve >=0.92). There was no
difference in diagnostic accuracy between techniques. The cutoff values for
optimal identification of significant fibrosis by transient elastography and 2
dimensional shear wave elastography were 9.6 kPa and 10.2 kPa, and for cirrhosis
19.7 kPa and 16.4 kPa. Negative predictive values were high for both groups, but
the positive predictive value for cirrhosis was >66% in the high-risk group vs
approximately 50% in the low-risk group. Evidence of alcohol-induced damage to
cholangiocytes, but not ongoing alcohol abuse, affected liver stiffness. The
collagen-proportionate area correlated with Ishak grades and accurately
identified individuals with significant fibrosis and cirrhosis. CONCLUSIONS: In a
prospective study of individuals at risk for liver fibrosis due to alcohol
consumption, we found elastography to be an excellent tool for diagnosing liver
fibrosis and for excluding (ruling out rather than ruling in) cirrhosis.
PMID- 26435271
TI - Endoplasmic Reticulum Stress in Hepatic Stellate Cells Promotes Liver Fibrosis
via PERK-Mediated Degradation of HNRNPA1 and Up-regulation of SMAD2.
AB - BACKGROUND & AIMS: Endoplasmic reticulum (ER) stress has been implicated in a
variety of diseases. Hepatic stellate cells (HSCs) contribute to the development
of liver fibrosis. Information on the link between ER stress and HSC activation
is scarce. We investigated the effects of ER stress in HSCs on the progression of
liver fibrosis and the regulation of this process in cells and mice. METHODS:
Proteins and messenger RNAs were measured in 2 sets of liver samples (n = 25 and
n = 44) collected from patients with chronic hepatitis C virus infection and/or
fibrosis. ER stress was induced in cells and mice using chemical agents.
Lentiviral vectors were constructed to express glucose-regulated protein 78
(GRP78; also known as HSPA5) or heterogeneous nuclear ribonucleoprotein A1
(HNRNPA1) from the alpha-smooth muscle actin promoter and injected into C57BL/6
mice for HSC-specific gene expression. Liver tissues and HSCs were collected from
mice or rats and analyzed using immunoblottings and quantitative reverse
transcription polymerase chain reaction. LX-2 cells were transfected with small
interfering RNAs, microRNA mimics, or overexpression vectors. RESULTS: Hepatic ER
stress was much higher in liver tissues from patients with severe vs mild
fibrosis. ER stress induced fibrogenic genes in HSCs. Targeted lentiviral
delivery of glucose-regulated protein 78 to HSCs in mice reduced fiber
accumulation in liver. Levels of SMAD2, but not SMAD3, were increased in fibrotic
liver tissues from patients or mice exposed to ER stress; small interfering RNA
mediated knockdown of SMAD2 reduced ER stress-mediated activation of HSCs. In rat
HSCs, ER stress increased levels of SMAD2 messenger RNA by decreasing levels of
microRNA 18a (MIR18A), an inhibitor of SMAD2 expression, rather than
transactivating the SMAD2 gene. ER stress-activated PKR-like endoplasmic
reticulum kinase, also known as EIF2AK3 (PERK) phosphorylated HNRNPA1, a protein
required for the maturational processing of primary MIR18A, at Thr51,
accelerating its degradation. Overexpression of HNRNPA1 (or its T51A mutant) in
HSCs of mice inhibited liver fibrosis. Severe fibrotic liver tissues from
patients had increased levels of phosphorylated PERK and reduced levels of
HNRNPA1 in HSCs, compared with mild fibrotic liver tissues. CONCLUSIONS: ER
stress in HSCs promotes liver fibrosis by inducing overexpression of SMAD2, via
dysregulation of MIR18A; this dysregulation is mediated by PERK phosphorylation
and destabilization of HNRNPA1.
PMID- 26435272
TI - Continuous chemical operations and modifications on magnetic gamma-Fe2O3
nanoparticles confined in nanoliter droplets for the assembly of fluorescent and
magnetic SiO2@gamma-Fe2O3.
AB - We present a microfluidic platform that allows undergoing different chemical
operations in a nanoliter droplet starting from the colloidal suspension of
magnetic iron oxide (gamma-Fe2O3) nanoparticles "NPs" (ferrofluid). These
operations include: mixing, flocculation, magnetic decantation, colloidal
redispersion, washing, surface functionalization, heating and colloidal assembly.
To prove the platform capabilities, we produced fluorescent and magnetic
nanoassemblies composed of fluorescent silica and magnetic NPs.
PMID- 26435273
TI - PDGFR-beta Plays a Key Role in the Ectopic Migration of Neuroblasts in Cerebral
Stroke.
AB - The neuroprotective agents and induction of endogenous neurogenesis remain to be
the urgent issues to be established for the care of cerebral stroke. Platelet
derived growth factor receptor beta (PDGFR-beta) is mainly expressed in neural
stem/progenitor cells (NSPCs), neurons and vascular pericytes of the brain;
however, the role in pathological neurogenesis remains elusive. To this end, we
examined the role of PDGFR-beta in the migration and proliferation of NSPCs after
stroke. A transient middle cerebral-arterial occlusion (MCAO) was introduced into
the mice with conditional Pdgfrb-gene inactivation, including N-PRbeta-KO mice
where the Pdgfrb-gene was mostly inactivated in the brain except that in vascular
pericytes, and E-PRbeta-KO mice with tamoxifen-induced systemic Pdgfrb-gene
inactivation. The migration of the DCX(+) neuroblasts from the subventricular
zone toward the ischemic core was highly increased in N-PRbeta-KO, but not in E
PRbeta-KO as compared to Pdgfrb-gene preserving control mice. We showed that
CXCL12, a potent chemoattractant for CXCR4-expressing NSPCs, was upregulated in
the ischemic lesion of N-PRbeta-KO mice. Furthermore, integrin alpha3
intrinsically expressed in NSPCs that critically mediates extracellular matrix
dependent migration, was upregulated in N-PRbeta-KO after MCAO. NSPCs isolated
from N-PRbeta-KO rapidly migrated on the surface coated with collagen type IV or
fibronectin that are abundant in vascular niche and ischemic core. PDGFR-beta was
suggested to be critically involved in pathological neurogenesis through the
regulation of lesion-derived chemoattractant as well as intrinsic signal of
NSPCs, and we believe that a coordinated regulation of these molecular events may
be able to improve neurogenesis in injured brain for further functional recovery.
PMID- 26435274
TI - Editorial Comment from Dr. Keoghane to Application of nephrostomy tubes with
balloon after percutaneous nephrolithotomy: A randomized controlled clinical
trial.
PMID- 26435275
TI - Retracted: Impact of Type 2 diabetes prevention programmes based on risk
identification and lifestyle intervention intensity strategies: a cost
effectiveness analysis.
AB - The following article, published online on 17 November 2015 in Wiley Online
Library (wileyonlinelibrary.com), has been retracted by agreement between the
authors, the journal Editor in Chief, Richard Holt and John Wiley & Sons Ltd. The
retraction has been agreed due the fact the authors have made Wiley aware that
there was an error in the way the diabetes prevention intervention effect was
implemented in this version of the model. The underlying model is not affected by
this error. However, the magnitude of the cost savings and health benefits are
substantially lower than stated. Reference 1 Breeze R, Thomas C, Squires H,
Brennan A, Greaves C, Diggle PJ, Brunner E, Tabak A, Preston L, Chilcott J.
Impact of Type 2 diabetes prevention programmes based on risk identification and
lifestyle intervention intensity strategies: a cost-effectiveness analysis.
Diabet Med 2015; doi: 10.1111/dme.12981.
PMID- 26435276
TI - In vitro anti-foot-and-mouth disease virus activity of magnesium oxide
nanoparticles.
AB - Foot-and-mouth disease (FMD) is an extremely contagious viral disease of cloven
hoofed animals that can lead to huge economic losses in the livestock production.
No antiviral therapies are available for treating FMD virus (FMDV) infections in
animals. The antiviral effects of magnesium oxide nanoparticles (MgO NPs) on the
FMDV were investigated in cell culture. The viability of the cells after MgO NP
treatment was determined using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide] assay. The direct effects of MgO NPs on the FMDV in
extracellular (virucidal assay) and also different stages of virus replication
(antiviral assay) were evaluated by plaque reduction assay. The results showed
that MgO NPs were safe at concentrations up to 250 ug/ml in the Razi Bovine
kidney cell line. The treatments with NPs indicated that the MgO NPs exerted in
vitro virucidal and antiviral activities. Plaque reduction assay revealed that
MgO NPs can inhibit FMDV by more than 90% at the early stages of infection such
as attachment and penetration but not after penetration. The results of this
study suggested that NPs might be applied locally as an antiviral agent in early
stages of infection in susceptible animals.
PMID- 26435277
TI - Biosynthesis of silver and platinum nanoparticles using orange peel extract:
characterisation and applications.
AB - This study focuses on the green synthesis of noble metal nanoparticles (silver
(Ag) and platinum (Pt)) and how the size and shape of the nanoparticles produced
can be controlled through changes in the initial pH value of the precursor
solution. The nanoparticles were characterised by ultra-violet-visible
spectroscopy, transmission electron microscopy and X-ray diffraction. This simple
and environmentally friendly method allows the synthesis of diverse
nanostructures in the absence of a surfactant or polymer to direct nanoparticle
growth, and without externally adding seed crystallites. The antibacterial
effects of Ag nanoparticles and catalytic properties of Pt nanoparticles were
explored for future promising biotechnological approaches in different fields.
PMID- 26435278
TI - Biosensing application of multiwall boron nitride nanotube-based nanoresonator
for detecting various viruses.
AB - This study explores the suitability of biosensors using multi-walled boron
nitride nanotubes (MW-BNNTs) with virus/bacterium attached at the free end of
cantilever through vibration analysis. Various viruses/bacteria having mass of
the order of zeptogram level are considered for obtaining resonance frequencies
of cantilevered triple-walled boron nitride nanotube (TW-BNNT) by means of a
continuum mechanics-based analytical approach. The simulation with various
viruses/bacteria attached at the tip of cantilevered TW-BNNT is carried out for
different lengths. The finite element method simulated resonance frequency values
are compared with results obtained from the analytical method by taking into
account the effective wall thickness of tubes and van der Waals interaction
between various BNNTs. A close proximity is observed between results obtained
from the two approaches, which further confirms the validity of the proposed
model. The obtained results suggest that shorter length TW-BNNT is more sensitive
for detecting viruses/bacteria having mass of zeptogram order.
PMID- 26435279
TI - Plumbagin-silver nanoparticle formulations enhance the cellular uptake of
plumbagin and its antiproliferative activities.
AB - Colloidal silver nanoparticles (AgNPs) have attracted much attention in recent
years as diagnostics and new drug delivery system in cancer medicine. To study
the effects of plumbagin (PLB), a relatively non-toxic napthaquinone isolated
from the roots of Plumbago indica in human cervical cancer cell line and
developed a formulation to enhance its cytotoxic activities. Silver nanoparticles
were synthesised by chemical reduction method and complexed with PLB. Both the
AgNPs and the complex PLB-AgNPs were characterised by dynamic light scattering,
high-resolution scanning electron microscopy and transmission electron
microscopy. The amount of PLB and PLB-AgNPs internalised was determined by ultra
violet-visible spectrophotometer. Cell inhibition was determined by
sulphorhodamine B assay. Mitotic index was determined by Wright-Giemsa staining.
Apoptosis induction was assessed by western blot using cleaved poly adenosine
diphosphate-ribose polymerase antibody. The scanning electron microscope analysis
indicated an average particle size of 32+/-8 nm in diameter. Enhanced
internalisation of PLB into the HeLa cells was observed in PLB-AgNPs. PLB
inhibited proliferation of cells with IC50 value of about 18+/-0.6 uM and blocked
the cells at mitosis in a concentration-dependent manner. PLB also inhibited the
post-drug exposure clonogenic survival of cells and induced apoptosis. The
antiproliferative, antimitotic and apoptotic activities were also found to be
increased when cells were treated with PLB-AgNPs. The authors results support the
idea that AgNP could be a promising and effective drug delivery system for
enhanced activity of PLB in cancer treatment.
PMID- 26435280
TI - Escherichia coli bacteria detection by using graphene-based biosensor.
AB - Graphene is an allotrope of carbon with two-dimensional (2D) monolayer
honeycombs. A larger detection area and higher sensitivity can be provided by
graphene-based nanosenor because of its 2D structure. In addition, owing to its
special characteristics, including electrical, optical and physical properties,
graphene is known as a more suitable candidate compared to other materials used
in the sensor application. A novel model employing a field-effect transistor
structure using graphene is proposed and the current-voltage (I-V)
characteristics of graphene are employed to model the sensing mechanism. This
biosensor can detect Escherichia coli (E. coli) bacteria, providing high levels
of sensitivity. It is observed that the graphene device experiences a drastic
increase in conductance when exposed to E. coli bacteria at 0-10(5) cfu/ml
concentration. The simple, fast response and high sensitivity of this
nanoelectronic biosensor make it a suitable device in screening and functional
studies of antibacterial drugs and an ideal high-throughput platform which can
detect any pathogenic bacteria. Artificial neural network and support vector
regression algorithms have also been used to provide other models for the I-V
characteristic. A satisfactory agreement has been presented by comparison between
the proposed models with the experimental data.
PMID- 26435281
TI - Three Phoma spp. synthesised novel silver nanoparticles that possess excellent
antimicrobial efficacy.
AB - The authors report extracellular mycosynthesis of silver nanoparticles (AgNPs) by
Phoma capsulatum, Phoma putaminum and Phoma citri. The AgNPs thus synthesised
were characterised by UV-visible spectrophotometer, Fourier transform infrared
spectroscopy, Nanosight LM20 and transmission electron microscopy, which
confirmed the synthesis of mostly spherical and polydisperse nanoparticles capped
with proteins. The size of AgNPs was found in the range of 10-80 , 5-80 and 5-90
nm with an average size of 31.85, 25.43 and 23.29 nm by P. capsulatum, P.
putaminum and P. citri, respectively. Further, potential antimicrobial activity
was reported against Aspergillus niger, Candida albicans, Salmonella
choleraesuis, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli.
The lowest minimal inhibitory concentration (MIC) (0.85 ug/ml) was reported for
AgNPs synthesised from P. citri against S. choleraesuis. However, AgNPs
synthesised from P. capsulatum showed the highest MIC (10.62 ug/ml) against S.
choleraesuis, P. aeruginosa and E. coli (clinical isolate). The same MIC values
(10.62 ug/ml) were also reported against P. aeruginosa and both clinical and
standard isolates of E. coli for AgNPs synthesised from P. citri. It was also
observed that all the silver nanoparticles showed remarkable antifungal and
antibacterial activity against these tested pathogens as compared with the
commercially available antifungal and antibacterial agents.
PMID- 26435282
TI - Biosynthesis, characterisation and antimicrobial activity of silver nanoparticles
using Hibiscus rosa-sinensis petals extracts.
AB - Green synthesis of metallic nanoparticles has lured the world from the chemical
and physical approaches owing to its rapid, non-hazardous and economic aspect of
production mechanism. In this study, silver nanoparticles (AgNPs) were
synthesised using petal extracts of Hibiscus rosa-sinensis. The AgNPs displayed
characteristic surface plasmon resonance peak at around 421 nm having a mean
particle size of 76.25+/-0.17 nm and carried a charge of -41+/-0.2 mV. The X-ray
diffraction patterns displayed typical peaks of face centred cubic crystalline
silver. The surface morphology was characterised by scanning electron microscopy
and atomic force microscopy. Fourier transform infrared spectroscopy studies
confirmed the surface modifications of the functional groups for the synthesis of
AgNPs. Furthermore, the synthesised AgNPs displayed proficient antimicrobial
activity against pathogenic strains of Vibrio cholerae, Escherichia coli,
Klebsiella pneumoniae and Staphylococcus aureus.
PMID- 26435283
TI - Preparation and in vitro investigation of antigastric cancer activities of
carvacrol-loaded human serum albumin nanoparticles.
AB - In this study, carvacrol-loaded human serum albumin (HSA) nanoparticles were
developed and characterised. Nanoparticles were prepared by desolvation and
emulsion/desolvation methods. Encapsulation efficiency (EE%) and loading capacity
(LC%) of nanoparticles prepared by desolvation method were 48.4 and 45.1%,
respectively. Carvacrol-loaded nanoparticles had 132+/-42 nm in diameter with
monomodal distribution. Carvacrol-loaded nanoparticles which is prepared by
emulsion/desolvation method had EE% and LC% of 32 and 32.3%, respectively, and
230+/-38 nm in size. The release of carvacrol from nanoparticles was monitored in
phosphate-buffered saline (pH=7.4), 100 rpm at 37 degrees C for 10 days. About
21.4% of carvacrol was released after 3 h from nanoparticles that were prepared
by desolvation method. In emulsion/desolvation method, 26.8% of total carvacrol
was released during 3 h of incubation. Cytotoxicity effect of loaded carvacrol
was assessed by 3-[4, 5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
(MTT) test on gastric cancer cells line (AGS). Cell line was exposed to the free
carvacrol, unloaded and carvacrol-loaded nanoparticles for 48 h. The half maximal
inhibitory concentration (IC50) for free carvacrol, unloaded and carvacrol-loaded
HSA nanoparticles were 30, 1070 and 120 ug/ml, respectively. In conclusion, the
results of this study showed applications of HSA nanoparticles for entrapment of
carvacrol and antigastric cancer activity. Moreover, loading of carvacrol in
combination with chemotherapy agents into the HSA nanoparticles may treat cancer
cells better than single drug loaded nanoparticles.
PMID- 26435284
TI - Biosynthesis of tellurium nanoparticles by Lactobacillus plantarum and the effect
of nanoparticle-enriched probiotics on the lipid profiles of mice.
AB - Hypercholesterolemia is an important risk factor contributing to atherosclerosis
and coronary heart disease. Lactic acid bacteria have attracted much attention
regarding their promising effect on serum cholesterol levels. Tellurium (Te) is a
rare element that has also gained considerable interest for its biological
effects. There have been some recent in vivo reports on the reduction effect of
Te on cholesterol content. In this study, Lactobacillus plantarum PTCC 1058 was
employed for the intracellular biosynthesis of Te NPs. The UV-visible spectrum of
purified NPs showed a peak at 214 nm related to the surface plasmon resonance of
the Te NPs. Transmission electron microscopy showed that spherical nanoparticles
without aggregation had the average size of 45.7 nm as determined by the laser
scattering method. The energy dispersive X-ray pattern confirmed the presence of
Te atoms without any impurities. A significant reduction was observed in group
which received L. plantarum with or without Te NPs during propylthiouracil and
cholesterol diet in compare with the control group which received just
propylthiouracil and cholesterol. The levels of triglycerides also remarkably
decrease (p<0.05) in mice given L. plantarum with intracellular Te NPs.
PMID- 26435285
TI - Optimisation of processing variables effective on self-assembly of folate
targeted Synpronic-based micelles for docetaxel delivery in melanoma cells.
AB - Polymeric micelles (PMs) were formulated as nano carriers for docetaxel intended
for both intravenous administration and improve therapeutic efficacy of the drug.
The PMs were formulated using folic acid conjugated Synpronic F127-cholesterol
copolymer and were optimised using a 2(3) full factorial design. The effects of
different formulation variables were evaluated on the particle size, entrapment
efficiency (EE), zeta potential and release efficiency of the micelles. The in
vitro cytotoxicity of DTX-loaded FA targeted micelles was studied on B16F10
melanoma cells which over expressed FA receptor. Among the studied single
factors, solvent type was the most effective parameter on the EE and release
efficiency. Polymer/drug ratio had the most considerable effect on the particle
size while, zeta potential was more affected by temperature. Finally, the PMs
with polymer/drug ratio of 12 prepared at 25 degrees C by dimethyl sulfoxide as
the dialyzing solvent was shown to be the optimum formulation with desirability
factor of 84.9%. The optimised formulation exhibited a particle size of 171.3 nm,
99.59% drug EE, zeta potential of -7.80 mV, drug release efficiency of about 70%
at 144 h and polydispersity index of 0.32. The MTT assay indicated DTX-loaded FA
targeted micelles were significantly more cytotoxic than non-targeted micelles
and free drug.
PMID- 26435286
TI - Catalytic role of traditional enzymes for biosynthesis of biogenic metallic
nanoparticles: a mini-review.
AB - Although the formation mechanism of biogenically metallic nanoparticles is
broadly associated to enzyme mediation, major attention has been given to the
role of proteins and peptides in oxido-reduction of metallic ions leading to
these nanostructures. Among the wide range of biomolecules that can act not only
as capping agents but also as non-enzymatic agents to form nanoparticles,
disulphide bridge-containing peptides and amino acids particularly stand out. The
literature proposes that they actively participate in the process of
nanoparticles' synthesis, with thiols groups and disulphide bridge moieties as
the reaction catalytic sites. Similarly, denaturated enzymes containing exposed S
S or S-H moieties are also able to reduce metallic ions to form nanoparticles.
This mini-review is focused on the biogenic synthesis of metallic nanoparticles
such as gold, silver, copper, platinum, palladium, lead and selenium, in which
proteins, peptides, reductases and even oxido-reductases act as non-enzymatic
catalysts of the reduction reaction, opening economically and ecologically
favourable perspectives in the nanoparticles synthesis field.
PMID- 26435287
TI - Editorial: The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: The
Operations Behind a Herculean Task.
PMID- 26435288
TI - Managing Multi-Center Recruitment in the PLCO Cancer Screening Trial.
AB - There were significant recruitment challenges specific to the PLCO Cancer
Screening Trial. Large numbers of participants were to be randomized from ten
catchment areas nationwide within time and budgetary constraints. The eligible
population was elderly and had to meet health and behavioral thresholds. Informed
consent was required to participate and be randomized to screening for three
cancers at periodic clinic visits or to a usual care arm that included no
clinical visits. Consenting required special efforts to fully explain the trial
and its potential scientific benefit to future patients with potentially no
benefits but possible harms to PLCO participants. Participation would include
continued follow-up for at least 13 years after randomization. Strong
collaborative investments were required by the NCI and screening centers (SCs) to
assure timely recruitment and appropriate racial participation. A trial-wide
pilot phase tested recruitment and protocol follow through at SCs and produced a
vanguard population of 11,406 participants. NCI announced the trial nationally in
advance of the pilot and followed with an even more intense collaborative role
with SCs for the main phase to facilitate trial-wide efficient and timely
recruitment. Special efforts to enhance recruitment in the main phase included
centralized and local monitoring of progress, cross-linking SCs to share
experiences in problem solving, centralized training, substantial additional
funding dedicated to recruitment and retention, including specialized programs
for minority recruitment, obtaining national endorsement by the American Cancer
Society, launching satellite recruitment and screening centers, including
minority focused satellites, and adding a new SC dedicated to minority
recruitment.
PMID- 26435290
TI - Cancer Cachexia: One Step Ahead.
AB - Cachexia is one of the most common manifestations in advanced cancer patients,
but too often it remains under- recognized and under-treated. Starvation is not
the same of cachexia. Cachexia is defined by "weight loss >5% over past 6 months
in absence of simple starvation or the combination of ongoing weight loss>2% with
BMI <20 or sarcopenia". The pathogenesis of cancer cachexia is not fully
understood, but inflammation and an increased catabolic response to a number of
cancer-related factors seem to represent the basis of any assumption. Early
diagnosis of a pre-cachectic or cachectic state is a key moment for the treatment
of this complex syndrome, in order to guarantee an adequate food intake and
suitable exercise and to interfere with the inflammatory processes that are
typical of cachexia. Therefore, one of the main aims is to identify those
patients most likely to develop the syndrome early. A multimodality baseline
approach to cancer cachexia addresses reversible clinical contributory factors.
There are currently no medicinal products that have a proven efficacy in the
medical approach to cancer cachexia. Recently, anamorelin, a synthetic orally
active ghrelin receptor agonist, showed promising results, but the best approach
to cancer cachexia probably remains an early multimodal interventions consisting
in nutritional intervention, exercise and rehabilitation program, and multi
target drug therapies. This review summarizes what we know and what still need to
know about cancer cachexia syndrome.
PMID- 26435289
TI - PLCO: Evolution of an Epidemiologic Resource and Opportunities for Future
Studies.
AB - The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a
large-scale, multi-institutional, randomized controlled trial, was launched in
1992 to evaluate the effectiveness of screening modalities for prostate, lung,
colorectal, and ovarian cancer. However, PLCO was additionally designed to serve
as an epidemiologic resource and the National Cancer Institute has invested
substantial resources over the years to accomplish this goal. In this report, we
provide a summary of changes to PLCO's follow-up after conclusion of the
screening phase of the trial and highlight recent data and biospecimen
collections, including ancillary studies, geocoding, administration of a new
medication use questionnaire, consent for linkage to Medicare, and additional
tissue collection that enhance the richness of the PLCO resource and provide
further opportunities for scientific investigation into the prevention, early
detection, etiology and treatment of cancer.
PMID- 26435291
TI - Copying of RNA Sequences without Pre-Activation.
AB - Template-directed incorporation of nucleotides at the terminus of a growing
complementary strand is the basis of replication. For RNA, this process can occur
in the absence of enzymes, if the ribonucleotides are first converted to an
active species with a leaving group. Thus far, the activation required a separate
chemical step, complicating prebiotically plausible scenarios. Here we show that
a combination of a carbodiimide and an organocatalyst induces near-quantitative
incorporation of any of the four ribonucleotides. Upon in situ activation,
adenosine monophosphate was found to also form oligomers in aqueous solution. So,
both de novo strand formation and sequence-specific copying can occur without an
artificial synthetic step.
PMID- 26435292
TI - Being in a critical illness-recovery process: a phenomenological hermeneutical
study.
AB - AIMS AND OBJECTIVE: The aim of this study was to describe and interpret the
essential meaning of the lived experiences of being in a critical illness
recovery process after a life-threatening condition. BACKGROUND: The critical
illness-recovery process after a life-threatening condition takes several years
and does not only include patients' experiences during intensive care. Previous
research has mainly focused on what critically ill patients recall. However, from
a phenomenological point of view, experiences are more than memories alone. To
plan and perform relevant health care and social support for patients who have
survived a life-threatening condition, a more profound understanding about their
lived experiences is needed. DESIGN AND METHOD: In this qualitative study, a
phenomenological hermeneutical approach was used. Interviews were conducted with
seven patients, two to four years after they had received care in an intensive
care unit in Sweden. RESULTS: The comprehensive understanding of the results
shows that the critical illness-recovery process after a life-threatening
condition means an existential struggle to reconcile with an unfamiliar body and
with ordinary life. This can be understood as an 'unhomelikeness' implying a
struggle to create meaning and coherence from scary and fragmented memories. The
previous life projects, such as work and social life become unfamiliar when the
patient's fragile and weak body is disobedient and brings on altered sensations.
CONCLUSIONS: Patients who survive a life-threatening condition have an immense
need for care and support during the entire critical illness-recovery process,
and also after the initial acute phase. They need a coherent understanding of
what happened, and support to be able to perform their changed life projects.
RELEVANCE TO CLINICAL PRACTICE: Supporting and caring for patients' recovery from
a life- threatening condition involves recognising the patients' struggle and
responding to their existential concerns.
PMID- 26435293
TI - Childhood-Onset Essential Hypertension and the Family Structure.
AB - The prevalence and effect of single-parent families in childhood-onset essential
hypertension (EH) is unknown. Children with EH and age-, sex-, and ethnicity
matched controls were enrolled. Family structure data were obtained by in-person
interview. A total of 148 families (76 hypertension probands, 72 control
probands; median 14 years) were prospective-ly enrolled in the study. Single
parent status was seen in 42% of the families--with and without EH (38% vs 46%,
P=.41; odds ratio, 0.7; 95% confidence interval, 0.4-1.4). After multivariable
analysis, a statistically significant sociofamilial contributor to the
development of childhood-onset EH was not identified. A significant number of
single-parent families (42%), the majority with single mothers, were found in our
pedigree study. Sociofamilial factors are known to contribute to the expression
of adult-onset EH, but findings in our study suggest that they appear to
contribute less in the expression of childhood-onset EH.
PMID- 26435294
TI - Synthesis and Anti-Hepatitis B Virus Evaluation of 7-Methoxy-3-heterocyclic
quinolin-6-ols.
AB - A series of novel 7-methoxy-3-heterocyclic quinolin-6-ol derivatives were
synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and
cytotoxicities in the HepG2.2.15 cell line. Five compounds, 14a, 15c, 15e, 16b,
and 16f, displayed excellent potency and selectivity toward the HBV, with IC50
values of less than 5.0 uM and selectivity index values of 11.0-71.5. Structure
activity relationship studies indicated that the 1,3,4-thiadiazole and
sulfinylmethyl derivatives showed the most potent activities against the HBV.
PMID- 26435295
TI - The impact of age on cerebral perfusion, oxygenation and metabolism during
exercise in humans.
AB - Age is one of the most important risk factors for dementia and stroke.
Examination of the cerebral circulatory responses to acute exercise in the
elderly may help to pinpoint the mechanisms by which exercise training can reduce
the risk of brain diseases, inform the optimization of exercise training
programmes and assist with the identification of age-related alterations in
cerebral vascular function. During low-to-moderate intensity dynamic exercise,
enhanced neuronal activity is accompanied by cerebral perfusion increases of ~10
30%. Beyond ~60-70% maximal oxygen uptake, cerebral metabolism remains elevated
but perfusion in the anterior portion of the circulation returns towards
baseline, substantively because of a hyperventilation-mediated reduction in the
partial pressure of arterial carbon dioxide (P aC O2) and cerebral
vasoconstriction. Cerebral perfusion is lower in older individuals, both at rest
and during incremental dynamic exercise. Nevertheless, the increase in the
estimated cerebral metabolic rate for oxygen and the arterial-internal jugular
venous differences for glucose and lactate are similar in young and older
individuals exercising at the same relative exercise intensities. Correction for
the age-related reduction in P aC O2 during exercise by the provision of
supplementary CO2 is suggested to remove ~50% of the difference in cerebral
perfusion between young and older individuals. A multitude of candidates could
account for the remaining difference, including cerebral atrophy, and enhanced
vasoconstrictor and blunted vasodilatory pathways. In summary, age-related
reductions in cerebral perfusion during exercise are partly associated with a
lower P aC O2 in exercising older individuals; nevertheless the cerebral
extraction of glucose, lactate and oxygen appear to be preserved.
PMID- 26435296
TI - Open-label study evaluating outpatient urethral sphincter injections of
onabotulinumtoxinA to treat women with urinary retention due to a primary
disorder of sphincter relaxation (Fowler's syndrome).
AB - OBJECTIVES: To assess the efficacy (defined as improvements in maximum urinary
flow rate [Qmax ] of >=50%, post-void residual urine volume [PVR] and scores on
the International Prostate Symptom Score [IPSS] questionnaire) and safety of
urethral sphincter injections of onabotulinumtoxinA in women with a primary
disorder of urethral sphincter relaxation, characterised by an elevated urethral
pressure profile (UPP) and specific findings at urethral sphincter
electromyography (EMG), i.e. Fowler's syndrome. PATIENTS AND METHODS: In this
open-label pilot Institutional Review Board-approved study, 10 women with a
primary disorder of urethral sphincter relaxation (elevated UPP, sphincter
volume, and abnormal EMG) presenting with obstructed voiding (five) or in
complete urinary retention (five) were recruited from a single tertiary referral
centre. Baseline symptoms were assessed using the IPSS, and Qmax and PVR were
measured. After 2% lidocaine injection, 100 U of onabotulinumtoxinA was injected
into the striated urethral sphincter, divided on either side, under EMG guidance.
Patients were reviewed at 1, 4 and 10 weeks after injection, and assessed using
the IPSS, Qmax and PVR measurements. The UPP was repeated at week 4. RESULTS: The
mean (range) patient age was 40 (25-65) years, and the mean symptom scores on the
IPSS improved from 25.6 to 14.1, and the mean 'bother' score reduced from 6.1 to
3.5 at week 10. As compared with a baseline mean Qmax of 8.12 mL/s in the women
who could void, the Qmax improved to 15.8 mL/s at week 10. Four of the five women
in complete retention could void spontaneously, with a mean Qmax of 14.3 mL/s at
week 10. The mean PVR decreased from 260 to 89 mL and the mean static UPP
improved from 113 cmH2 O at baseline to 90 cmH2 O. No serious side-effects were
reported. Three women with a history of recurrent urinary tract infections
developed a urinary tract infection. There were no reports of stress urinary
incontinence. Seven of the 10 women opted to return for repeat injections.
CONCLUSIONS: This pilot study shows an improvement in patient-reported lower
urinary tract symptoms, and the objective parameters of Qmax , PVR and UPP, at 10
weeks after urethral sphincter injections of onabotulinumtoxinA. No serious side
effects were reported. This treatment could represent a safe outpatient treatment
for young women in retention due to a primary disorder of urethral sphincter
relaxation. However, a larger study is required to confirm the findings of this
pilot study.
PMID- 26435297
TI - Novel population-based study finding higher than reported hepatocellular
carcinoma incidence suggests an updated approach is needed.
AB - Hepatocellular carcinoma (HCC) incidence is rising rapidly in many developed
countries. Primary epidemiological data have invariably been derived from cancer
registries that are heterogeneous in data quality and registration methodology;
many registries have not adopted current clinical diagnostic criteria for HCC and
still rely on histology for classification. We performed the first population
based study in Australia using current diagnostic criteria, hypothesizing that
HCC incidence may be higher than reported. Incident cases of HCC (defined by
American Association for the Study of Liver Diseases diagnostic criteria or
histology) were prospectively identified over a 12-month period (2012-2013) from
the population of Melbourne, Australia. Cases were captured from multiple
sources: admissions to any of Melbourne's seven tertiary hospitals; attendances
at outpatients; and radiology, pathology, and pharmacy services. Our cohort was
compared to the Victorian Cancer Registry (VCR) cohort (mandatory notified cases)
for the same population and period, and incidence rates were compared for both
cohorts. There were 272 incident cases (79% male; median age: 65 years)
identified. Cirrhosis was present in 83% of patients, with hepatitis C virus
infection (41%), alcohol (39%), and hepatitis B virus infection (22%) the
commonest etiologies present. Age-standardized HCC incidence (per 100,000,
Australian Standard Population) was 10.3 (95% confidence interval [CI]: 9.0-11.7)
for males and 2.3 (95% CI: 1.8 to 3.0) for females. The VCR reported
significantly lower rates of HCC: 5.3 (95% CI: 4.4 to 6.4) and 1.0 (95% CI: 0.7
to 1.5) per 100,000 males and females respectively (P < 0.0001). CONCLUSIONS: HCC
incidence in Melbourne is 2-fold higher than reported by cancer registry data
owing to under-reporting of clinical diagnoses. Adoption of current diagnostic
criteria and additional capture sources will improve registry completeness.
Chronic viral hepatitis and alcohol remain leading causes of cirrhosis and HCC.
PMID- 26435298
TI - Traumatic brain injury in Africa in 2050: a modeling study.
AB - BACKGROUND AND PURPOSE: Our aim was to provide estimates of traumatic brain
injury (TBI) in 2050 for the African population by region, sex and age strata.
METHODS: A literature search was performed in October 2014 in PubMed for
population-based studies of TBI in different geographical locations. Articles
were selected from Kenya (model 1), New Zealand (model 2) and the USA (model 3).
In model 1, rates of road traffic injury in Kenya were used to estimate TBI rates
in the African continent. Models 2 and 3 used existing TBI incidence estimates
from other locations to estimate the burden of TBI for Africa in 2050. The 2050
African population, as projected by the United Nations, was used as a base
population. RESULTS: Based on rates from model 1, the estimated total TBI count
in Africa in 2050 is 5.98 +/- 0.03 million, with the highest count in eastern
(2.04 +/- 0.01 million) and lowest count in southern (0.15 +/- 0.00 million)
Africa. A higher TBI count is predicted by models 2 (14.25 +/- 0.75 million) and
3 (10.40 +/- 0.02 million). Estimated TBI count is highest for males aged 15-34
(5.47 +/- 0.55 million in model 2 and 3.21 +/- 0.13 million in model 3).
CONCLUSIONS: Projected estimates of TBI in Africa are high, with a burden of
anywhere between approximately 6 and 14 million new cases in 2050. This
emphasizes the importance of developing accurate surveillance systems of TBI at a
population level and public health measures to mitigate the risk and burden of
TBI.
PMID- 26435300
TI - A comparison of recommendations for pharmacologic thromboembolism prophylaxis
after caesarean delivery from three major guidelines.
AB - OBJECTIVE: Guidelines for pharmacologic obstetric venous thromboembolism (VTE)
prophylaxis from the American Congress of Obstetricians (ACOG), the Royal College
of Obstetricians and Gynaecologists (RCOG), and the American College of Chest
Physicians (Chest) vary significantly. The objective of this study was to
determine the practical implications of these recommendations in terms of
prophylaxis rates for a tertiary obstetric population. STUDY DESIGN: Cross
sectional. SETTING: Tertiary referral hospital. POPULATION: Patients post
operative day 1 after caesarean delivery. METHODS: This cross-sectional study
evaluated rates of pharmacologic prophylaxis for women based on RCOG, ACOG, and
Chest recommendations. Medical, obstetric, and demographic risk factors for
thromboembolism were reviewed for individual patients. Rates of prophylaxis based
on each of the guidelines with 95% confidence intervals were calculated. OUTCOME
MEASURE: Recommended pharmacologic prophylaxis. RESULTS: About 293 patients were
included in the analysis. Under RCOG guidelines, 85.0% of patients would receive
post-caesarean pharmacologic prophylaxis [95% confidence interval (CI) 80.5
88.6%] compared with 1.0% of patients under ACOG guidelines (95% CI 0.3-3.0%) and
34.8% of patients under Chest guidelines (95% CI 29.6-40.4%). Caesarean during
labour, obesity, advanced maternal age, pre-eclampsia, and multiple gestation
were among the most commonrisk factors. CONCLUSION: Recommended prophylaxis
differed significantly. Under ACOG recommendations a small minority of patients
would receive prophylaxis, whereas under RCOG recommendations a large majority of
patients would receive low-molecular-weight heparin. Given the large differences
in prophylaxis rates for post-caesarean thromboprophylaxis based on different
guidelines, further research is urgently needed to compare the risks and benefits
of recommendations. TWEETABLE ABSTRACT: Recommendations from major society
guidelines for post-caesarean thromboprophylaxis differ greatly.
PMID- 26435299
TI - Thiol-ene Photocrosslinking of Cytocompatible Resilin-Like Polypeptide-PEG
Hydrogels.
AB - A range of chemical strategies have been used for crosslinking recombinant
polypeptide hydrogels, although only a few have employed photocrosslinking
approaches. Here, we capitalize on the novel insect protein, resilin, and the
versatility of click reactions to introduce a resilin-like polypeptide (RLP) that
is capable of photoinitiated thiol-ene crosslinking. Lysine residues of the RLP
were functionalized with norbornene acid as confirmed via 1H-NMR spectroscopy.
The RLPNs were subsequently photocrosslinked with multi-arm PEG thiols in the
presence of a photoinitiator to form elastic hybrid hydrogels. The crosslinking
reaction and resulting RLP-PEG networks demonstrated cytocompatibility with human
mesenchymal stem cells in both 2D cell-adhesion and 3D photoencapsulation
studies.
PMID- 26435301
TI - Imaging and Clinical Characteristics Predict Near-Term Disablement From Bone
Metastases: Implications for Rehabilitation.
AB - OBJECTIVE: To distinguish which patients with bone metastases are at risk for
near-term disablement in order to assist clinicians in assessing the
appropriateness of referrals for rehabilitation services. DESIGN: Prospective
cohort study. SETTING: National Cancer Institute-designated comprehensive cancer
center imbedded in a tertiary medical center. PARTICIPANTS: Data were collected
from members (n=78) of a patient cohort (N=311) with stage IIIB or IV non-small
cell lung cancer or extensive-stage small-cell lung cancer who developed new or
progressive imaging-confirmed bone metastases during the 2-year course of the
study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional
capabilities were assessed at 3- to 4-week intervals over the study's 2-year
duration with the Activity Measure for Post-Acute Care Computer Adaptive Testing.
RESULTS: Seventy-eight participants developed new or progressive bone metastases
during the study. Most were men, and 83% had non-small-cell lung cancer.
Metastases were most frequently located in the ribs (n=62), pelvis (n=49), or the
thoracic (n=60) and lumbar spine (n=44). While neither the number of bone
metastases nor their specific location was associated with near-term changes in
patient mobility, their association with pain or a focal neurologic deficit was
strongly associated with large declines in mobility. Similarly, patients whose
imaging studies revealed new metastases and the expansion of established
metastases were more likely to lose mobility. CONCLUSIONS: The total burden,
specific locations, and overall distribution of bone metastases did not predict
disablement. Patients with lung cancer-associated bone metastases are at markedly
increased risk for declining mobility when their metastases are expanding in size
and increasing in number, or are associated with pain or with new neurologic
deficits.
PMID- 26435302
TI - Using Wearable Sensors and Machine Learning Models to Separate Functional Upper
Extremity Use From Walking-Associated Arm Movements.
AB - OBJECTIVE: To improve measurement of upper extremity (UE) use in the community by
evaluating the feasibility of using body-worn sensor data and machine learning
models to distinguish productive prehensile and bimanual UE activity use from
extraneous movements associated with walking. DESIGN: Comparison of machine
learning classification models with criterion standard of manually scored videos
of performance in UE prosthesis users. SETTING: Rehabilitation hospital training
apartment. PARTICIPANTS: Convenience sample of UE prosthesis users (n=5) and
controls (n=13) similar in age and hand dominance (N=18). INTERVENTIONS:
Participants were filmed executing a series of functional activities; a trained
observer annotated each frame to indicate either UE movement directed at
functional activity or walking. Synchronized data from an inertial sensor
attached to the dominant wrist were similarly classified as indicating either a
functional use or walking. These data were used to train 3 classification models
to predict the functional versus walking state given the associated sensor
information. Models were trained over 4 trials: on UE amputees and controls and
both within subject and across subject. Model performance was also examined with
and without preprocessing (centering) in the across-subject trials. MAIN OUTCOME
MEASURE: Percent correct classification. RESULTS: With the exception of the
amputee/across-subject trial, at least 1 model classified >95% of test data
correctly for all trial types. The top performer in the amputee/across-subject
trial classified 85% of test examples correctly. CONCLUSIONS: We have
demonstrated that computationally lightweight classification models can use
inertial data collected from wrist-worn sensors to reliably distinguish
prosthetic UE movements during functional use from walking-associated movement.
This approach has promise in objectively measuring real-world UE use of
prosthetic limbs and may be helpful in clinical trials and in measuring response
to treatment of other UE pathologies.
PMID- 26435303
TI - Combined theoretical and time-resolved photoluminescence investigations of
[Mo6Bri8Br(a)6]2- metal cluster units: evidence of dual emission.
AB - The combined time-resolved photoluminescence (PL) and theoretical study performed
on luminescent [Mo6Br(i)8Br(a)6](2-)-based systems unambiguously shows that their
NIR-luminescence is due to at least two emissive states. By quantum chemical
studies, we show for the first time that important geometrical relaxations occur
at the triplet states either by the outstretching of an apex away from the square
plane of the Mo6 octahedron or by the elongation of one Mo-Mo bond. Experimental
PL measurements demonstrate that the external environment (counter-ions, crystal
packing) of the cluster has a noticeable impact on its relaxation processes.
Temperature and excitation wavelength dependence of the two components of the
luminescence spectra is representative of multiple competitive de-excitation
processes in contradiction with Kasha's rule. Our results also demonstrate that
the relaxation processes before and after emission can be tracked via fast time
resolved spectroscopy. They also show that the surroundings of the luminescent
cluster unit and the excitation wavelength could be modulated for target
applications.
PMID- 26435307
TI - Making Dimethylamino a Transformable Directing Group by Nickel-Catalyzed C-N
Borylation.
AB - The dimethylamino (Me2N) group is arguably the most versatile functional group
capable of highly efficient and site-selective directed aromatic
functionalizations at the ortho-, meta-, and para-positions depending on reaction
conditions. While the repertoire of Me2N-directed reactions is growing at a rapid
pace, the lack of a general method to transform this group to other
functionalities hampers its wider application in organic synthesis. Here we
report nickel-catalyzed C-N borylations of aryl- and benzyl-dimethylamines that
permit the conversion of a huge library of largely underutilized Me2N-containing
organic molecules into various functional molecules by taking advantage of the
wealth of existing C-B functionalization methods.
PMID- 26435308
TI - Sample extraction techniques for biological samples: recent advances and novel
applications.
PMID- 26435309
TI - Modification of a commercial gas chromatography isotope ratio mass spectrometer
for on-line carbon isotope dilution: Evaluation of its analytical characteristics
for the quantification of organic compounds.
AB - We describe the instrumental modification of a commercial gas chromatography
isotope ratio mass spectrometer (GC-IRMS) and its application for on-line carbon
isotope dilution. The main modification consisted in the addition of a constant
flow of enriched (13)CO2 diluted in helium after the chromatographic column
through the splitter holder located inside the chromatographic oven of the
instrument. In addition, and in contrast to the conventional mode of operation of
GC-IRMS instruments where the signal at m/z 45 is amplified 100-fold with respect
to the signal at m/z 44, the same signal amplification was used in both Faraday
cups at m/z 44 and 45. Under these conditions isotope ratio precision for the
ratio 44/45 was around 0.05% RSD (n=50). The evaluation of the instrument was
performed with mixtures of organic compounds including 11 n-alkanes, 16 PAHs, 12
PCBs and 3 benzothiophenes. It was observed that compounds of very different
boiling points could be analysed without discrimination in the injector when a
Programmable Temperature Vaporizer (PTV) injector was employed. Moreover, the
presence of heteroatoms (Cl or S) in the structure of the organic compounds did
not affect their combustion efficiency and therefore the trueness of the results.
Quantitative results obtained for all the analytes assayed were excellent in
terms of precision (<3% RSD) and accuracy (average relative error<=4%) and what
is more important using a single and simple generic internal standard for
quantification.
PMID- 26435310
TI - Introduction to "Comparison between the efficiencies of columns packed with fully
and partially porous C18-bonded silica materials" by F. Gritti, A. Cavazzini, N.
Marchetti, G. Guiochon [J. Chromatogr. A 1157 (2007) 289-303].
PMID- 26435311
TI - Development and validation of methodologies for the quantification of
phytosterols and phytosterol oxidation products in cooked and baked food
products.
AB - Chromatography-mass spectrometry (GC-MS) methodologies for the analysis of the
main phytosterols (PS) and phytosterol oxidation products (POPs) present in 19
different foodstuffs cooked or baked using margarines with or without added plant
sterols are presented. Various methods for fat extraction were evaluated to allow
the GC-MS analysis of large numbers of prepared vegetable, fish and meat
products, egg and bakery items in a practically feasible manner. The optimized
methods resulted in a good sensitivity and allowed the analysis of both PS and
POPs in the broad selection of foods at a wide range of concentrations.
Calibration curves for both PS and POPs showed correlation coefficients (R(2))
better than 0.99. Detection limits were below 0.24mgkg(-1) for PS and 0.02mgkg(
1) for POPs, respectively. Average recovery data were between 81% and 105.1% for
PS and between 65.5 and 121.8% for POPs. Good results were obtained for within-
and between-day repeatability, with most values being below 10%. Entire sample
servings were analyzed, avoiding problems with inhomogeneity and making the
method an exact representation of the typical use of the food by the consumer.
PMID- 26435312
TI - Separation of bimodal high density polyethylene using multidimensional high
temperature liquid chromatography.
AB - High-temperature two-dimensional liquid chromatography (HT 2D-LC) using HT-HPLC
as first dimension and HT-SEC as second dimension holds enormous potential to
investigate the distribution according to molar mass and chemical composition of
bimodal high density polyethylene (BiHDPE), as it avoids drawbacks of
crystallization-based techniques. In this study, we have stepwise optimized the
chromatographic parameters of 1D, comprising gradient slope and temperature,
using model homo- and copolymers of ethylene with the aim to minimize the impact
of molar mass on the compositional separation. Then the HT-HPLC was hyphenated to
HT-SEC and optimum conditions for the volume of the sample transfer loop were
probed with regard to the resolution of BiHDPE into the individual constituents
HDPE and LLDPE. A particular important aspect was the use of infrared (IR)
detection, and the demands it puts on the chromatographic aspects: We have shown
that IR detection can be successfully applied in HT 2D-LC of BiHDPE, which is
broadly distributed with regard to short chain branching and molar mass, only
when the separation in 2D is optimized with regard to chromatographic resolution.
As final result a bimodality is evident in the contour and the 3D surface plots
as well as in both HPLC and SEC projections generated from HT 2D-LC.
PMID- 26435313
TI - Effervescence and graphitized multi-walled carbon nanotubes assisted
microextraction for natural antioxidants by ultra high performance liquid
chromatography with electrochemical detection and quadrupole time-of-flight
tandem mass spectrometry.
AB - In this article, effervescence and graphitized multi-walled carbon nanotubes
assisted microextraction was first developed for the extraction of antioxidants
in hawthorn samples. The use of an effervescent tablet composed of sodium
dihydrogen phosphate, sodium carbonate and micro-scale carboxyl graphitized multi
walled carbon nanotubes (extraction sorbent) was the core of the method. In this
study, ultra high performance liquid chromatography coupled with electrochemical
detection and quadrupole time-of-flight tandem mass spectrometry was performed
for qualitative and quantitative analyses of target analytes in hawthorn
foodstuffs. Several experimental factors, such as amount of effervescent salts,
the sorbent, elution time and elution solvent, were systematically assessed.
Under the optimized conditions, a good linearity with R values better than 0.9980
was obtained. The detection limits estimated at a signal-to-noise ratio of 3:1
were ranging from 0.01 to 0.18ng/mL. These results suggested that the proposed
method could be an alternative and promising sample preparation tool in future
food analysis.
PMID- 26435314
TI - Gel-assisted crystallization of [Ir4(IMe)7(CO)H10](2+) and [Ir4(IMe)8H9](3+)
clusters derived from catalytic glycerol dehydrogenation.
AB - The two title clusters were formed during iridium-catalyzed glycerol
dehydrogenation and display a remarkably high NHC content. They were crystallized
in either agarose or polyethylene oxide gel matrices, while more conventional
crystallization techniques proved unsuccessful. Cluster [Ir4(IMe)8H9](3+), with a
net charge of +3, was only crystallizable with a polyoxometalate Keggin trianion.
The crystal packing of this intercluster compound is discussed. Computational
studies position the iridium hydrides and provide insights into the bonding.
PMID- 26435315
TI - Sterilization Resistance of Bacterial Spores Explained with Water Chemistry.
AB - Bacterial spores can survive for long periods without nutrients and in harsh
environmental conditions. This survival is influenced by the structure of the
spore, the presence of protective compounds, and water retention. These
compounds, and the physical state of water in particular, allow some species of
bacterial spores to survive sterilization schemes with hydrogen peroxide and UV
light. The chemical nature of the spore core and its water has been a subject of
some contention and the chemical environment of the water impacts resistance
paradigms. Either the spore has a glassy core, where water is immobilized along
with other core components, or the core is gel-like with mobile water diffusion.
These properties affect the movement of peroxide and radical species, and hence
resistance. Deuterium solid-state NMR experiments are useful for examining the
nature of the water inside the spore. Previous work in our lab with spores of
Bacillus subtilis indicate that, for spores, the core water is in a more
immobilized state than expected for the gel-like core theory, suggesting a glassy
core environment. Here, we report deuterium solid-state NMR observations of the
water within UV- and peroxide-resistant spores from Bacillus pumilus SAFR-032.
Variable-temperature NMR experiments indicate no change in the line shape after
heating to 50 degrees C, but an overall decrease in signal after heating to 100
degrees C. These results show glass-like core dynamics within B. pumilus SAFR-032
that may be the potential source of its known UV-resistance properties. The
observed NMR traits can be attributed to the presence of an exosporium containing
additional labile deuterons that can aid in the deactivation of sterilizing
agents.
PMID- 26435316
TI - Novel Symbol Learning-Induced Stroop Effect: Evidence for a Strategy-Based,
Utility Learning Model.
AB - The automaticity level and attention priority/strategy are two major theories
that have attempted to explain the mechanism underlying the Stroop effect.
Training is an effective way to manipulate the experience with the two dimensions
(ink color and color word) in the Stroop task. In order to distinguish the above
two factors (the automaticity or attention/strategy), we revised the training
paradigm of MacLeod's study (J Exp Psychol Learn Mem Cogn 14(1):126-135, 1988) by
adding a control condition for the Stroop task on Chinese. We found that with
training, the changing pattern for the Stroop effect was similar in Stroop tasks
in novel symbols and in Chinese, showing markedly increasing interference and
marginally decreasing facilitation. The current findings support the strategy
based learning account at early stages of novel learning of written symbols.
PMID- 26435317
TI - Corrigendum: Sound Packing DNA: packing open circular DNA with low-intensity
ultrasound.
PMID- 26435318
TI - On the correlation between microscopic structural heterogeneity and embrittlement
behavior in metallic glasses.
AB - In order to establish a relationship between microstructure and mechanical
properties, we systematically annealed a Zr-based bulk metallic glass (BMG) at
100 ~ 300 degrees C and measured their mechanical and thermal properties. The as
cast BMG exhibits some ductility, while the increase of annealing temperature and
time leads to the transition to a brittle behavior that can reach nearly-zero
fracture energy. The differential scanning calorimetry did not find any
significant changes in crystallization temperature and enthalpy, indicating that
the materials still remained fully amorphous. Elastic constants measured by
ultrasonic technique vary only slightly with respect to annealing temperature and
time, which does obey the empirical relationship between Poisson's ratio and
fracture behavior. Nanoindentation pop-in tests were conducted, from which the
pop-in strength mapping provides a "mechanical probe" of the microscopic
structural heterogeneities in these metallic glasses. Based on stochastically
statistic defect model, we found that the defect density decreases with
increasing annealing temperature and annealing time and is exponentially related
to the fracture energy. A ductile-versus-brittle behavior (DBB) model based on
the structural heterogeneity is developed to identify the physical origins of the
embrittlement behavior through the interactions between these defects and crack
tip.
PMID- 26435319
TI - Expansion dynamics in a one-dimensional hard-core boson model with three-body
interactions.
AB - Using the adaptive time-dependent density matrix renormalization group method, we
numerically investigate the expansion dynamics of bosons in a one-dimensional
hard-core boson model with three-body interactions. It is found that the bosons
expand ballistically with weak interaction, which are obtained by local density
and the radius Rn. It is shown that the expansion velocity V, obtained from Rn =
Vt, is dependent on the number of bosons. As a prominent result, the expansion
velocity decreases with the enhancement of three-body interaction. We further
study the dynamics of the system, which quenches from the ground state with two
thirds filling, the results indicate the expansion is also ballistic in the
gapless phase regime. It could help us detect the phase transition in the system.
PMID- 26435320
TI - Imaging Local Heating and Thermal Diffusion of Nanomaterials with Plasmonic
Thermal Microscopy.
AB - Measuring local heat generation and dissipation in nanomaterials is critical for
understanding the basic properties and developing applications of nanomaterials,
including photothermal therapy and joule heating of nanoelectronics. Several
technologies have been developed to probe local temperature distributions in
nanomaterials, but a sensitive thermal imaging technology with high temporal and
spatial resolution is still lacking. Here, we describe plasmonic thermal
microscopy (PTM) to image local heat generation and diffusion from nanostructures
in biologically relevant aqueous solutions. We demonstrate that PTM can detect
local temperature change as small as 6 mK with temporal resolution of 10 MUs and
spatial resolution of submicrons (diffraction limit). With PTM, we have
successfully imaged photothermal generation from single nanoparticles and
graphene pieces, studied spatiotemporal distribution of temperature surrounding a
heated nanoparticle, and observed heating at defect sites in graphene. We further
show that the PTM images are in quantitative agreement with theoretical
simulations based on heat transport theories.
PMID- 26435321
TI - Lysine Methyltransferase SETD7 (SET7/9) Regulates ROS Signaling through
mitochondria and NFE2L2/ARE pathway.
AB - Reactive oxygen species (ROS) homeostasis requires stringent regulation. ROS
imbalance, especially ROS accumulation, has profound implications in various
disease pathogenesis. Lysine methylation of histone and non-histone proteins has
been implicated in various cellular responses. The main objective of this study
is to investigate the role of SET domain containing lysine methyltransferase
SETD7 (SET7/9) in the regulation of ROS-mediated signaling. Here we report that
inhibition of SETD7 with siRNA or a SETD7 small molecule inhibitor in both
macrophages and a human bronchial epithelial cell line (Beas-2B) were able to
counter NF-KB-induced oxidative stress and pro-inflammatory cytokine production.
Meanwhile, inhibition of SETD7 elevates mitochondria antioxidant functions via
negative regulation of PPARGC1A and NFE2L2. Using a co-expression system and
purified proteins, we detected direct interaction between SETD7 and NFE2L2. These
results indicate that lysine methylation by SETD7 is important for the fine
tuning of ROS signaling through its regulation on pro-inflammatory responses,
mitochondrial function and the NFE2L2/ARE pathway. Up-regulation of multiple
antioxidant genes and improved ROS clearance by inhibition of SETD7 suggests the
potential benefit of targeting SETD7 in treating ROS-associated diseases.
PMID- 26435322
TI - Ezrin is a Major Regulator of Membrane Tension in Epithelial Cells.
AB - Plasma membrane tension is responsible for a variety of cellular functions such
as motility, cell division, and endocytosis. Since membrane tension is dominated
by the attachment of the actin cortex to the inner leaflet of the plasma
membrane, we investigated the importance of ezrin, a major cross-linker of the
membrane-cytoskeleton interface, for cellular mechanics of confluent MDCK II
cells. For this purpose, we carried out ezrin depletion experiments and also
enhanced the number of active ezrin molecules at the interface. Mechanical
properties were assessed by force indentation experiments followed by membrane
tether extraction. PIP2 micelles were injected into individual living cells to
reinforce the linkage between plasma membrane and actin-cortex, while weakening
of this connection was reached by ezrin siRNA and administration of the
inhibitors neomycin and NSC 668394, respectively. We observed substantial
stiffening of cells and an increase in membrane tension after addition of PIP2
micelles. In contrast, reduction of active ezrin led to a decrease of membrane
tension accompanied by loss of excess surface area, increase in cortical tension,
remodelling of actin cytoskeleton, and reduction of cell height. The data confirm
the importance of the ezrin-mediated connection between plasma membrane and
cortex for cellular mechanics and cell morphology.
PMID- 26435323
TI - Inhibition of myostatin in mice improves insulin sensitivity via irisin-mediated
cross talk between muscle and adipose tissues.
AB - BACKGROUND/OBJECTIVE: In mice, a high-fat diet (HFD) induces obesity, insulin
resistance and myostatin production. We tested whether inhibition of myostatin in
mice can reverse these HFD-induced abnormalities. SUBJECTS/METHODS: C57BL/6 mice
were fed a HFD for 16 weeks including the final 4 weeks some mice were treated
with an anti-myostatin peptibody. Body composition, the respiratory exchange
ratio plus glucose and insulin tolerance tests were examined. Myostatin knock
down in C2C12 cells was performed using small hairpin RNA lentivirus. Adipose
tissue-derived stem cells were cultured to measure their responses to conditioned
media from C2C12 cells lacking myostatin, or to recombinant myostatin or irisin.
Isolated peritoneal macrophages were treated with myostatin or irisin to
determine whether myostatin or irisin induce inflammatory mechanisms. RESULTS: In
HFD-fed mice, peptibody treatment stimulated muscle growth and improved insulin
resistance. The improved glucose and insulin tolerances were confirmed when we
found increased muscle expression of p-Akt and the glucose transporter, Glut4. In
HFD-fed mice, the peptibody suppressed macrophage infiltration and the expression
of proinflammatory cytokines in both the muscle and adipocytes. Inhibition of
myostatin caused the conversion of white (WAT) to brown adipose tissue, whereas
stimulating fatty acid oxidation and increasing energy expenditure. The related
mechanism is a muscle-to-fat cross talk mediated by irisin. Myostatin inhibition
increased peroxisome proliferator-activated receptor gamma, coactivator 1alpha
expression and irisin production in the muscle. Irisin then stimulated WAT
browning. Irisin also suppresses inflammation and stimulates macrophage
polarization from M1 to M2 types. CONCLUSIONS: These results uncover a metabolic
pathway from an increase in myostatin that suppresses irisin leading to the
activation of inflammatory cytokines and insulin resistance. Thus, myostatin is a
potential therapeutic target to treat insulin resistance of type II diabetes as
well as the shortage of brown/beige fat in obesity.
PMID- 26435324
TI - IL-10 gene transfer upregulates arcuate POMC and ameliorates hyperphagia, obesity
and diabetes by substituting for leptin.
AB - BACKGROUND: Obesity and metabolic syndrome are the major risk factors for
cardiovascular disease. Obesity is caused by increased food intake and/or
decreased energy expenditure. Leptin potently inhibits food intake and promotes
energy expenditure. These effects of leptin involve the activation of
proopiomelanocortin (POMC) neurons in the hypothalamus arcuate nucleus (ARC).
Disruption of leptin signaling in POMC neuron is considered one of the major
causes for obesity. AIMS: The present study aimed to examine whether
overexpression of interleukin-10 (IL-10) could substitute for the leptin action
and ameliorate obesity in leptin-deficient Lep(ob/ob) mice. DESIGN: Adeno
associated virus (AAV) expressing murine IL-10 (AAV-mIL-10) was injected into the
skeletal muscle to overexpress IL-10 in mice. These mice were subsequently
subjected to analysis of body weight, food intake, glucose metabolism and
underlying mechanisms. RESULTS: In Lep(ob/ob) mice, AAV-IL-10 ameliorated
hyperphagia, obesity, glucose intolerance and insulin resistance, as well as
attenuated tumor necrosis factor-alpha expression. The IL-10 treatment also
improved glucose-induced insulin release. Furthermore, IL-10 treatment increased
POMC mRNA expression in ARC and phosphorylation of signal transducer and
activator of transcription-3 (STAT3) in ARC and white adipose tissue (WAT). In
neuron-specific STAT3-null mice that exhibited obesity and hyperphagia, AAV-mIL
10 administration failed to affect food intake, body weight and phosphorylation
of STAT3 in WAT. CONCLUSIONS: These results demonstrate that peripheral
overexpression of IL-10 induces STAT3 phosphorylation in ARC POMC neurons, and
thereby ameliorates hyperphagia and obesity caused by leptin deficiency. IL-10
gene transfer may provide an effective approach for preventing progression of
metabolic syndrome due to leptin resistance.
PMID- 26435325
TI - Apigenin induced apoptosis in esophageal carcinoma cells by destruction membrane
structures.
AB - Apigenin has shown to have killing effects on some kinds of solid tumor cells.
However, the changes in cell membrane induced by apigenin on subcellular- or
nanometer-level were still unclear. In this work, human esophageal cancer cells
(EC9706 and KYSE150 cells) were employed as cell model to detect the cytotoxicity
of apigenin, including cell growth inhibition, apoptosis induction, membrane
toxicity, etc. MTT assay showed that apigenin could remarkably inhibit the growth
and proliferation in both types of cells. Annexin V/PI-based flow cytometry
analysis showed that the cytotoxic effects of apigenin in KYSE150 cells were
mainly through early apoptosis induction, while in EC9706 cells, necrosis, and
apoptosis were both involved in cell death. The morphological and ultrastructural
properties induced by apigenin were investigated at single cellular- or nanometer
level using atomic force microscopy (AFM). Additionally, lactate dehydrogenase
(LDH) leakage was measured to assess the changes in membrane permeability. The
results indicated that apigenin increased the membrane permeability and caused
leakage of LDH, which was consistent with damages on membrane ultrastructure
detected by AFM. Therefore, membrane toxicity, including membrane ultrastructure
damages and enhanced membrane permeability, played vital roles in apigenin
induced human esophageal cancer cell apoptosis. SCANNING 38:322-328, 2016. (c)
2015 Wiley Periodicals, Inc.
PMID- 26435326
TI - Iron-Binding Capacity of Defatted Rice Bran Hydrolysate and Bioavailability of
Iron in Caco-2 Cells.
AB - The present study was aimed at utilizing defatted rice bran (DRB) protein as an
iron-binding peptide to enhance iron uptake in humans. DRB samples were treated
with Alcalase and Flavourzyme, and the total extractable peptides were
determined. Furthermore, the iron-binding capacities of the DRB protein
hydrolysates were determined, whereas iron bioavailability studies were conducted
using an in vitro digestion and absorption model (Caco-2 cells). The results
showed that the DRB protein hydrolysates produced by combined Alcalase and
Flavourzyme hydrolysis had the best iron-binding capacity (83%) after 90 min of
hydrolysis. The optimal hydrolysis time to produce the best iron-uptake in Caco-2
cells was found to be 180 min. The results suggested that DRB protein
hydrolysates have potent iron-binding capacities and may enhance the
bioavailability of iron, hence their suitability for use as iron-fortified
supplements.
PMID- 26435327
TI - Ultrafine FePd Nanoalloys Decorated Multiwalled Cabon Nanotubes toward Enhanced
Ethanol Oxidation Reaction.
AB - Ultrafine iron-palladium (FePd) nanoalloys deposited on gamma-Fe2O3, FePd-Fe2O3,
further anchored on carboxyl multiwalled carbon nanotubes (MWNTs-COOH), FePd
Fe2O3/MWNTs, were successfully synthesized by a facile one-pot solution based
method as thermally decomposing palladium acetylacetonate (Pd(acac)2) and iron
pentacarbonyl (Fe(CO)5) in a refluxing dimethylformamide solution in the presence
of MWNTs-COOH. A 3.65 fold increase of peak current density was observed in
cyclic voltammetry (CV) for ethanol oxidation reaction (EOR) compared with that
of Pd/MWNTs after normalizing to Pd mass. The greatly enhanced tolerance
stability toward poisoning species and largely reduced charge transfer resistance
were also obtained in chronoamperometry and electrochemical impedance
spectroscopy due to the downward shifted d-band center of FePd alloy, easily
formed oxygen containing species on Fe2O3, and the stabilizing role of the MWNTs.
PMID- 26435328
TI - Pathogenesis of solitary right aortic arch: a mass effect hypothesis based on
observations of serial human embryonic sections.
AB - In general, solitary right aortic arch carries the left-sided ductus arteriosus
communicating between the left subclavian and pulmonary arteries or the right
sided ductus connecting the descending aorta to the left pulmonary artery. Serial
sections of fifteen 5- to 6-week-old embryos and ten 8- to 9-week-old fetuses
suggested that the pathogenesis was unrelated to inversion due to dysfunction in
gene cascades that control the systemic left/right axis. With inversion,
conversely, the ductus or the sixth pharyngeal arch artery should connect to the
right pulmonary artery. The disappearance of the right aortic arch started before
the caudal migration of the aortic attachment of the ductus. Sympathetic nerve
ganglia developed immediately posterior to both aortae, with a single embryonic
specimen showing a large ganglion at the midline close to the union of the aortic
arches. These ganglia may interfere with blood flow through the distal left arch,
resulting in the ductus ending at the descending aorta behind the oesophagus. In
another fetus examined, a midline shift of the ductus course resulted in the
trachea curving posteriorly. Therefore, solitary right arch is likely to
accompany abnormalities of the surrounding structures. The timing and site of the
obstruction should be different between types: an almost midline obstruction near
the aortic union needed for the development of the left-sided ductus and a distal
obstruction near the left subclavian arterial origin needed for the development
of the right-sided ductus. A mass effect of the sympathetic ganglia may explain
the pathogenesis of any type of anomalous ductus arteriosus shown in previous
reports of the solitary right arch.
PMID- 26435329
TI - Morphology of the greater palatine grooves of the hard palate: a cone beam
computed tomography study.
AB - BACKGROUND: There is increasing frequency of dentoalveolar and palatal implants
placed in the posterior maxilla for prosthodontic and orthodontic purposes. The
purpose of this study is to provide information on the location and morphology of
the greater palatine grooves (GPG) in the hard palate and to promote awareness of
this structure. METHODS: Eighty-nine cone beam computed tomography (CBCT) scans
were analysed for the presence of a groove, crest or bridging. RESULTS: This
study on the morphology of the GPG in the maxillary first and second molar
regions showed three distinct appearances: (1) no palatal groove; (2) one palatal
groove; (3) two palatal grooves. The detection frequency of no palatal groove in
the first molar region was 60%, 34% had one groove and 6% having two grooves. The
detection frequency of no palatal groove in the second molar region was 72%, 26%
had one groove and 2% had two grooves. The number of crests in the first and
second molar regions ranged from 0 to 3. CONCLUSIONS: The present study
demonstrates a great variation in morphology of the GPG of the hard palate.
Knowledge of the GPG will decrease possible complications of implant surgery,
particularly palatal implant surgery and to not confuse the GPG with pathology.
PMID- 26435330
TI - Genetic diversity of clinical Mycobacterium avium subsp. hominissuis and
Mycobacterium intracellulare isolates causing pulmonary diseases recovered from
different geographical regions.
AB - Mycobacterium avium complex (MAC) infections are increasing annually in many
countries. MAC strains are the most common nontuberculous mycobacterial pathogens
isolated from respiratory samples and predominantly consist of two species,
Mycobacterium avium and Mycobacterium intracellulare. The aim of this study was
to analyze the molecular epidemiology and genetic backgrounds of clinical MAC
isolates collected from The Netherlands, Germany, United States, Korea and Japan.
Variable numbers of tandem repeats (VNTR) analysis was used to examine the
genetic relatedness of clinical isolates of M. avium subsp. hominissuis (n=261)
and M. intracellulare (n=116). Minimum spanning tree and unweighted pair group
method using arithmetic averages analyses based on the VNTR data indicated that
M. avium subsp. hominissuis isolates from Japan shared a high degree of genetic
relatedness with Korean isolates, but not with isolates from Europe or the United
States, whereas M. intracellulare isolates did not show any specific clustering
by geographic origin. The findings from the present study indicate that strains
of M. avium subsp. hominissuis, but not M. intracellulare, exhibit geographical
differences in genetic diversity and imply that MAC strains may have different
sources, routes of transmission and perhaps clinical manifestations.
PMID- 26435331
TI - Effects of eribulin on microtubule binding and dynamic instability are
strengthened in the absence of the betaIII tubulin isotype.
AB - Eribulin mesylate (Halaven) is a microtubule-targeted anticancer drug used to
treat patients with metastatic breast cancer who have previously received a
taxane and an anthracycline. It binds at the plus ends of microtubules and has
been shown to suppress plus end growth selectively. Because the class III beta
tubulin isotype is associated with resistance to microtubule targeting drugs, we
sought to determine how betaIII tubulin might mechanistically influence the
effects of eribulin on microtubules. We found that while [(3)H]eribulin bound to
bovine brain soluble tubulin depleted of betaIII tubulin in a manner similar to
that of unfractionated tubulin, it bound to plus ends of microtubules that were
depleted of betaIII-depleted tubulin with a maximal stoichiometry (20 +/- 3
molecules per microtubule) higher than that of unfractionated microtubules (9 +/-
2 molecules per microtubule). In addition, eribulin suppressed the dynamic
instability behavior of betaIII-depleted microtubules more strongly than and in a
manner different from that of microtubules containing betaIII tubulin.
Specifically, with betaIII tubulin present in the microtubules, 100 nM eribulin
suppressed the growth rate by 32% and marginally reduced the catastrophe
frequency (by 17%) but did not modulate the rescue frequency. However, in the
absence of betaIII tubulin, eribulin not only reduced the growth rate but also
strongly reduced the shortening rate (by 43%) and the catastrophe and the rescue
frequencies (by 49 and 32%, respectively). Thus, when present in microtubules,
betaIII tubulin substantially weakens the effects of eribulin.
PMID- 26435332
TI - Solar Thermochemical Energy Storage Through Carbonation Cycles of SrCO3/SrO
Supported on SrZrO3.
AB - Solar thermochemical energy storage has enormous potential for enabling cost
effective concentrated solar power (CSP). A thermochemical storage system based
on a SrO/SrCO3 carbonation cycle offers the ability to store and release high
temperature (~1200 degrees C) heat. The energy density of SrCO3/SrO systems
supported by zirconia-based sintering inhibitors was investigated for 15 cycles
of exothermic carbonation at 1150 degrees C followed by decomposition at 1235
degrees C. A sample with 40 wt % of SrO supported by yttria-stabilized zirconia
(YSZ) shows good energy storage stability at 1450 MJ m(-3) over fifteen cycles at
the same cycling temperatures. After further testing over 45 cycles, a decrease
in energy storage capacity to 1260 MJ m(-3) is observed during the final cycle.
The decrease is due to slowing carbonation kinetics, and the original value of
energy density may be obtained by lengthening the carbonation steps.
PMID- 26435334
TI - Comparative effectiveness of Pilates and yoga group exercise interventions for
chronic mechanical neck pain: quasi-randomised parallel controlled study.
AB - OBJECTIVES: To determine the effectiveness of Pilates and yoga group exercise
interventions for individuals with chronic neck pain (CNP). DESIGN: Quasi
randomised parallel controlled study. SETTING: Community, university and private
practice settings in four locations. PARTICIPANTS: Fifty-six individuals with CNP
scoring >=3/10 on the numeric pain rating scale for >3 months (controls n=17,
Pilates n=20, yoga n=19). INTERVENTIONS: Exercise participants completed 12 small
group sessions with modifications and progressions supervised by a
physiotherapist. MAIN OUTCOME MEASURES: The primary outcome measure was the Neck
Disability Index (NDI). Secondary outcomes were pain ratings, range of movement
and postural measurements collected at baseline, 6 weeks and 12 weeks. Follow-up
was performed 6 weeks after completion of the exercise classes (Week 18).
RESULTS: NDI decreased significantly in the Pilates {baseline: 11.1 [standard
deviation (SD) 4.3] vs Week 12: 6.8 (SD 4.3); mean difference -4.3 (95%
confidence interval -1.64 to -6.7); P<0.001} and yoga groups [baseline: 12.8 (SD
7.4) vs Week 12: 8.1 (SD 5.6); mean difference -4.7 (95% confidence interval -2.1
to -7.4); P<0.00], with no change in the control group. Pain ratings also
improved significantly. Moderate-to-large effect sizes (0.7 to 1.8) and low
numbers needed to treat were found. There were no differences in outcomes between
the exercise groups or associated adverse effects. No improvements in range of
movement or posture were found. CONCLUSIONS: Pilates and yoga group exercise
interventions with appropriate modifications and supervision were safe and
equally effective for decreasing disability and pain compared with the control
group for individuals with mild-to-moderate CNP. Physiotherapists may consider
including these approaches in a plan of care. CLINICAL TRIAL REGISTRATION NUMBER:
ClinicalTrials.gov NCT01999283.
PMID- 26435333
TI - Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and
Ultrasound for Treating Liver Cancer.
AB - Repurposing of existing cancer drugs to overcome their physical limitations, such
as insolubility, represents an attractive strategy to achieve enhanced
therapeutic efficacy and broaden the range of clinical applications. Such an
approach also promises to offer substantial cost savings in drug development
efforts. Here we repurposed FDA-approved topical agent bexarotene (Targretin),
currently in limited use for cutaneous manifestations of T-cell lymphomas, and re
engineer it for use in solid tumor applications by forming self-assembling
nanobubbles. Physico-chemical characterization studies of the novel prodrug
nanobubbles demonstrated their stability, enhanced target cell internalization
capability, and highly controlled release profile in response to application of
focused ultrasound energy. Using an in vitro model of hepatocellular carcinoma
and an in vivo large animal model of liver ablation, we demonstrate the
effectiveness of bexarotene prodrug nanobubbles when used in conjunction with
catheter-based ultrasound, thereby highlighting the therapeutic promise of this
trimodal approach.
PMID- 26435336
TI - Key interactions of surfactants in therapeutic protein formulations: A review.
AB - Proteins as amphiphilic, surface-active macromolecules, demonstrate substantial
interfacial activity, which causes considerable impact on their multifarious
applications. A commonly adapted measure to prevent interfacial damage to
proteins is the use of nonionic surfactants. Particularly in biotherapeutic
formulations, the use of nonionic surfactants is ubiquitous in order to prevent
the impact of interfacial stress on drug product stability. The scope of this
review is to convey the current understanding of interactions of nonionic
surfactants with proteins both at the interface and in solution, with specific
focus to their effects on biotherapeutic formulations.
PMID- 26435335
TI - The Association of Statin Use with Age-Related Macular Degeneration Progression:
The Age-Related Eye Disease Study 2 Report Number 9.
AB - PURPOSE: To evaluate the association of statin use with progression of age
related macular degeneration (AMD). DESIGN: Preplanned, prospective cohort study
within a controlled clinical trial of oral supplementation for age-related eye
diseases. PARTICIPANTS: Age-Related Eye Disease Study 2 (AREDS2) participants,
aged 50 to 85 years. METHODS: Factors, including age, gender, smoking status,
aspirin use, and history of diabetes, hypertension, heart disease, angina, and
stroke-all known to be associated with statin use-were included in a logistic
regression model to estimate propensity scores for each participant. Age-adjusted
proportional hazards regression models, with and without propensity score
matching, were performed to evaluate the association of statin use with
progression to late AMD. Analyses adjusting for the competing risk of death were
also performed. MAIN OUTCOME MEASURES: Baseline and annual stereoscopic fundus
photographs were assessed centrally by masked graders for the development of late
AMD, either neovascular AMD or geographic atrophy (GA). RESULTS: Of the 3791
participants (2462 with bilateral large drusen and 1329 with unilateral late AMD
at baseline), 1659 (43.8%) were statin users. The overall analysis, with no
matching of propensity scores and no adjustment for death as a competing risk,
showed that statin use was not associated with progression to late AMD (hazard
ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When
matched for propensity scores and adjusted for death as a competing risk, the
result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29).
Furthermore, subgroup analyses of persons with or without late AMD at baseline
and the various components of late AMD (neovascular AMD, central GA, or any GA)
also showed no statistically significant association of statin use with
progression to AMD. CONCLUSIONS: Statin use was not statistically significantly
associated with progression to late AMD in the AREDS2 participants, and these
findings are consistent with findings in the majority of previous studies.
Statins have been demonstrated to reduce the risk of cardiovascular disease, but
our data do not provide evidence of a beneficial effect on slowing AMD
progression.
PMID- 26435337
TI - Electrophoretic RNA genomic profiles of Brazilian Picobirnavirus (PBV) strains
and molecular characterization of a PBV isolated from diarrheic calf.
AB - Picobirnavirus (PBV) belongs to the family Picobirnaviridae. PBV are a group of
emerging non-enveloped viruses, with a bisegmented double-stranded RNA genome
that can infect a wide range of hosts. This study reports the occurrence of PBV
in fecal samples from five Brazilian dairy cattle herds. From the 289 stool
samples of individual calves analyzed by silver-stained polyacrylamide gel
electrophoresis (ss-PAGE) the PBV was detected in 8.3 % (24/289), of which 10.2%
(18/176) had diarrheic consistency. Of the 24 positive samples in ss-PAGE, 5
(20.8%) of them showed a small electrophoretic profile and 19 (79.2%) samples had
large profile. From the 24 positives samples by ss-PAGE, 15 (62.5%) were
successfully amplified (201 bp) using GI specific primers targeting the RdRp gene
of PBV. The analysis of nucleotide identity matrix revealed that the bovine PBV
strain identified in this study, showed the highest nucleotide identity (81%)
with PBV strain detected in turkey (MD-2010/HM803965). This is the first
nucleotide sequence of a bovine PBV strain in the American continent and the
first detection of small genome profile of PBV-like strains in bovine hosts.
PMID- 26435338
TI - Purification and characterization of saxitoxin from Mytilus chilensis of southern
Chile.
AB - In the current communication we describe an innovative method to purify saxitoxin
(STX), a toxin presents in contaminated muscle of Mylitus chilensis extracted in
the southern part of Chile, using a liquid chromatographic methodology based on
ionic pairs. The STX was extracted using HCl and treated with ammonium sulfate
following a treatment with trichloroacetic acid and hexane/diethyl ether (97/3).
The samples were analyzed by a semi-preparative HPLC in order to collect pure
fractions of STX and these fractions were eluted in solid-phase cationic
interchange SCX extraction columns. The purified STX was stable and homogeneous
and its identity was confirmed by LC-MS-MS, which demonstrated a high quality
purification of STX, without presence of analogs such as neosaxitoxin (Neo) and
decarbamoyl saxitoxin (dcSTX). The STX biological activity was analyzed in a
bioassay in mice model and compared to the standard STX produced by the FDA and
no significant differences were observed.
PMID- 26435339
TI - Effects of long-term administration of Senna occidentalis seeds on the
hematopoietic tissue of rats.
AB - Senna occidentalis (S. occidentalis) is a toxic leguminous plant that
contaminates crops and has been shown to be toxic to several animal species. All
parts of the plant are toxic, but most of the plant's toxicity is due to its
seeds. Despite its toxicity, S. occidentalis is widely used for therapeutic
purposes in humans. The aim of the present work was to investigate, for the first
time, the effects of the chronic administration of S. occidentalis seeds on
hematopoietic organs, including the bone marrow and spleen. Fifty male Wistar
rats were divided into five groups of 10 animals. Rats were treated with diets
containing 0% (control), 0.5% (So0.5), 1% (So1), or 2% (So2) S. occidentalis
seeds for a period of 90 days. Food and water were provided ad libitum, except to
pair-fed (PF) group which received the same amount of ration to those of So2
group, however free of S. occidentalis seeds. It was verified that rats treated
with 2% S. occidentalis seeds presented changes in hematological parameters. The
blood evaluation also showed a significant decrease of the Myeloid/Erythroid
(M/E) ratio. Chronic treatment with S. occidentalis promoted a reduction in the
cellularity of both the bone marrow and spleen. Additionally, we observed changes
in bone marrow smears, iron stores and spleen hemosiderin accumulation.
Histological analyses of bone marrow revealed erythroid hyperplasia which was
consistent with the increased reticulocyte count. These findings suggest that the
long-term administration of S. occidentalis seeds can promote blood toxicity.
PMID- 26435340
TI - Characterization of the antinociceptive effect of PhTx3-4, a toxin from
Phoneutria nigriventer, in models of thermal, chemical and incisional pain in
mice.
AB - Venom-derived peptides constitute a unique source of drug prototypes for the pain
management. Many of them can modulate voltage-gated calcium channels that are
central in the processing of pain sensation. PhTx3-4 is a peptide isolated from
Phoneutria nigriventer venom, which blocks high voltage-activated calcium
channels with low specificity, thereby leading to neuroprotection in models of
ischemia in vitro. The aim of the present work was evaluating the potential of
intrathecal PhTx3-4 in the reversal of different nociceptive states in mice,
furthermore assessing the potential of PhTx3-4 in triggering motor side effects.
We found that bellow 100 pmol/site, PhTx3-4 did not cause major motor side
effects. By comparison, omega-conotoxin MVIIA and omega-conotoxin MVIIC triggered
motor side effects at the doses of 10 and 100 pmol/site, respectively. Also,
PhTx3-4 (30 pmol/site) caused no significant alterations in the forced locomotor
activity test (rotarod) and in the exploratory activity test (versamax). In a
model of inflammatory persistent pain (formalin test), PhTx3-4 reversed
nociceptive behavior both pre or post-administered, although this effect was
observed only at the inflammatory phase of the test and not at the neurogenic
phase. Comparatively, omega-conotoxin MVIIC was effective only when post
administered in the formalin test. Nonetheless, PhTx3-4 treatment was devoid of
action in acute nociceptive thermal model (hotplate test), whereas morphine
showed efficacy in this test. Efficacy of PhTx3-4 in the formalin test was
associated with inhibition of formalin-induced glutamate release in the
cerebrospinal fluid. PhTx3-4, but not omega-conotoxin MVIIC, reversed NMDA
induced nociceptive behavior indicating a putative role of PhTx3-4 at ionotropic
glutamate receptors. Finally, we observed efficacy of PhTx3-4 in ameliorating
mechanical hypersensitivity induced by paw incision, a post-operative and more
clinically relevant pain model. Taken together, our data show that PhTx3-4
possesses antinociceptive effect in different models of pain in mice, suggesting
that this toxin may serve as drug prototype for pain control.
PMID- 26435341
TI - Recombinant expression and predicted structure of parborlysin, a cytolytic
protein from the Antarctic heteronemertine Parborlasia corrugatus.
AB - The heteronemertine Parborlasia corrugatus contains a cytolytic protein,
parborlysin, which after extensive purification was found by Edman sequencing to
be a mixture of several homologues. To investigate this microheterogeneity and
enable the analysis of single toxins, we have obtained seven parborlysin isoform
genes from P. corrugatus collected in Antarctica. Total RNA was isolated from the
homogenized head region and parborlysin genes were identified from a cDNA library
using degenerate primers. The translated sequences reveal that the isoforms are ~
10 kDa basic (pI ~ 10) proteins of which all but one harbour six cysteine
residues. We generated a model of the three dimensional structure of
parborlysins, which suggests that they are composed of five alpha-helical
segments that include large, exposed hydrophobic surfaces. Finally, we
constructed plasmids and inserted them into Escherichia coli to obtain
overexpressed amino- or carboxy-terminal polyhistidine-tagged parborlysin
isoforms fused to the third domain of the E. coli periplasmic-protein TolA to
facilitate toxin isolation. One of the isoforms adversely affected growth in the
E. coli expressing it. Although we succeeded in isolating one of the recombinant
parborlysin constructs, it lacked haemolytic activity.
PMID- 26435342
TI - cDNA cloning and expression of Contractin A, a phospholipase A2-like protein from
the globiferous pedicellariae of the venomous sea urchin Toxopneustes pileolus.
AB - Venomous sea urchins contain various biologically active proteins that are toxic
to predators. Contractin A is one such protein contained within the globiferous
pedicellariae of the venomous sea urchin Toxopneustes pileolus. This protein
exhibits several biological activities, such as smooth muscle contraction and
mitogenic activity. N-terminal amino acid residues of Contractin A have been
determined up to 37 residues from the purified protein. In this study, we cloned
cDNA for Contractin A by reverse transcription-PCR using degenerate primers
designed on the basis of its N-terminal amino acid sequence. Analysis of the cDNA
sequence indicated that Contractin A is composed of 166 amino acid residues
including 31 residues of a putative signal sequence, and has homology to the
sequence of phospholipase A2 from various organisms. In this study, recombinant
Contractin A was expressed in Escherichia coli cells, and the protein was
subjected to an assay to determine lipid-degrading activity using
carboxyfluorescein-containing liposomes. As a result, Contractin A was found to
exhibit Ca(2+)-dependent release of carboxyfluorescein from the liposomes,
suggesting that Contractin A has phospholipase A2 activity, which may be closely
associated with its biological activities.
PMID- 26435344
TI - A Cell ELISA for the quantification of MUC1 mucin (CD227) expressed by cancer
cells of epithelial and neuroectodermal origin.
AB - Quantitative analysis of MUC1, a cell membrane associated mucin, expressed by
intact cells of epithelial origin previously has been limited to flow cytometry,
which requires using large quantities of cells and antibodies. Here, for the
first time, we report the development of a novel Cellular-based Enzyme Linked
Immunosorbent Assay (Cell ELISA) to quantify the expression of MUC1 by cell lines
of epithelial and neuroectodermal origin using an antibody recognizing a specific
tandem repeat found in the extracellular domain of MUC1. In contrast to flow
cytometry, this method requires a much lower number of cells. We report here the
results obtained from two variants of this Cell ELISA in live and fixed cells. We
found that the Cell ELISA in live cells was not sensitive enough to detect a
difference in MUC1 levels between the normal cells and tumor cells. However, we
found that Cell ELISA in fixed cells followed by whole cell staining was a
dependable method of MUC1 level detection in the normal and tumor cells showing
significantly higher levels of MUC1 receptor in the tumor cells when compared to
the normal controls. Therefore, we conclude that the Cell ELISA in fixed cells is
an efficient method for quantifying the expression of MUC1 by epithelial and
neuroectodermal cancer cell lines.
PMID- 26435345
TI - T cell response to FVIII.
AB - Several lines of evidence indicate that the immune response to Factor VIII
(FVIII) in patients with hemophilia A is T cell-dependent. This review highlights
the link between the epitope specificity of FVIII-specific T cells and their
potential roles in different categories of patients. FVIII-specific T cells able
to recognize wild-type (i.e. therapeutic) FVIII but not the mutated self FVIII of
hemophilia patients have been identified in patients with mild/moderate
hemophilia carrying some point mutations. Such T cells likely contribute to the
higher frequency of neutralizing anti-FVIII antibodies (inhibitors) development
in these patients. In contrast, as yet no T cells have been identified that can
differentiate between FVIII molecules with non-hemophilia-causing single amino
acid variants encoded by non-synonymous single-nucleotide polymorphisms in the F8
gene. Other mechanisms are therefore still to be identified that will explain the
clinically noted differences in the incidence of inhibitor development between
patients of different races who are known to have differences at these sites.
Beside information about the mechanism of inhibitor development, the analysis of
FVIII-specific T cells has provided tools to develop novel diagnostic and
therapeutic approaches, such as the generation of FVIII-specific regulatory T
cells that may be useful in preventing or suppressing the immune response to
FVIII.
PMID- 26435343
TI - Tolerance and immune suppression in the tumor microenvironment.
AB - The concept of immunological tolerance has guided and permeated much of modern
immunology. Ray Owen's ground-breaking observations in twin cattle provided the
first mechanistic explanation for tolerance to self-molecules and established
tolerance as a beneficial process that protects the host against autoreactivity.
However, his studies also opened the door to understanding that tolerance may be
detrimental, such as occurs when cancer cells induce tolerance/immune suppression
resulting in inhibition of anti-tumor immunity. This article briefly traces the
early history of the field of tumor immunology with respect to tolerance, and
then focuses on a relatively recently identified population of cells called
myeloid-derived suppressor cells (MDSCs). MDSC are instrumental in causing
tolerance/immune suppression in individuals with cancer. They are present in most
individuals with cancer and because of their potent immune suppressive activity
are a major deterrent to natural anti-tumor immunity and a significant obstacle
to immunotherapy.
PMID- 26435346
TI - Senescence as a general cellular response to stress: A mini-review.
AB - Cellular senescence was initially described as the phenomenon of limited cell
divisions that normal cells in culture can undergo during long-term-cultivation.
Later it was found that senescence may be induced by various stress factors. The
intriguing resemblance between stress-induced and replicative senescence makes
questionable the distinction between both types and suggests that the cellular
senescence is a common outcome of stress response. Growing evidences support the
idea that stress-induced senescence is the cell-type specific.
PMID- 26435347
TI - Absence of caveolin-1 leads to delayed development of chronic lymphocytic
leukemia in EMU-TCL1 mouse model.
AB - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the
United States. The tissue microenvironment, specifically the lymph nodes,
influences the biological and clinical behavior of CLL cells. Gene expression
profiling of CLL cells from peripheral blood, bone marrow, and lymph nodes
revealed Cav-1 as one of the genes that might be involved in the pathogenesis of
CLL. We have previously reported that the knockdown of Cav-1 in primary CLL cells
exhibits a significant decrease in cell migration and immune synapse formation.
However, the precise role of Cav-1 in CLL initiation and progression in vivo is
not known. Therefore, we decreased the expression of Cav-1 in vivo by breeding
EMU-TCL1 with cav-1 knockout mice. We observed a significant decrease in the
number of CLL cells and rate of proliferation of CLL cells in spleen, liver, and
bone marrow from EMU-TCL1-Cav1(-/+) and EMU-TCL1-Cav1(-/-) mice as compared with
EMU-TCL1 mice. In addition, there was a significant increase in survival of EMU
TCL1-Cav1(-/+) and EMU-TCL1-Cav1(-/-) compared with EMU-TCL1 mice.
Mechanistically, we observed a decrease in MAPK-Erk signaling measured by p-Erk
levels in EMU-TCL1-Cav1(-/+) mice when compared with EMU-TCL1-Cav(wt/wt).
Together these results indicate that decreased Cav-1 in EMU-TCL1 mice
significantly delays the onset of CLL and decreases leukemic progression by
inhibiting MAPK-Erk signaling, suggesting a role for Cav-1 in the proliferation
and progression of CLL.
PMID- 26435348
TI - Pac-Man for biotechnology: co-opting degrons for targeted protein degradation to
control and alter cell function.
AB - Protein degradation in normal living cells is precisely regulated to match the
cells' physiological requirements. The selectivity of protein degradation is
determined by an elaborate degron-tagging system. Degron refers to an amino acid
sequence that encodes a protein degradation signal, which is oftentimes a poly
ubiquitin chain that can be transferred to other proteins. Current understanding
of ubiquitination dependent and independent protein degradation processes has
expanded the application of degrons for targeted protein degradation and novel
cell engineering strategies. Recent findings suggest that small molecules
inducing protein association can be exploited to create degrons that target
proteins for degradation. Here, recent applications of degron-based targeted
protein degradation in eukaryotic organisms are reviewed. The degron mediated
protein degradation represents a rapidly tunable methodology to control protein
abundance, which has broad application in therapeutics and cellular function
control and monitoring.
PMID- 26435349
TI - Brain size and thermoregulation during the evolution of the genus Homo.
AB - Several hypotheses have been proposed to explain the evolution of an
energetically costly brain in the genus Homo. Some of these hypotheses are based
on the correlation between climatic factors and brain size recorded for this
genus during the last millions of years. In this study, we propose a
complementary climatic hypothesis that is based on the mechanistic connection
between temperature, thermoregulation, and size of internal organs in endothermic
species. We hypothesized that global cooling during the last 3.2 my may have
imposed an increased energy expenditure for thermoregulation, which in the case
of hominids could represent a driver for the evolution of an expanded brain, or
at least, it could imply the relaxation of a negative selection pressure acting
upon this costly organ. To test this idea, here we (1) assess variation in the
energetic costs of thermoregulation and brain maintenance for the last 3.2 my,
and (2) evaluate the relationship between Earth temperature and brain maintenance
cost for the same period, taking into account the effects of body mass and fossil
age. We found that: (1) the energetic cost associated with brain enlargement
represents an important fraction (between 47.5% and 82.5%) of the increase in
energy needed for thermoregulation; (2) fossil age is a better predictor of brain
maintenance cost than Earth temperature, suggesting that (at least) another
factor correlated with time was more relevant than ambient temperature in brain
size evolution; and (3) there is a significant negative correlation between the
energetic cost of brain and Earth temperature, even after accounting for the
effect of body mass and fossil age. Thus, our results expand the current
energetic framework for the study of brain size evolution in our lineage by
suggesting that a fall in Earth temperature during the last millions of years may
have facilitated brain enlargement.
PMID- 26435350
TI - Gut morphology and hepatic oxidative status of European sea bass (Dicentrarchus
labrax) juveniles fed plant feedstuffs or fishmeal-based diets supplemented with
short-chain fructo-oligosaccharides and xylo-oligosaccharides.
AB - The effects of short-chain fructo-oligosaccharides (scFOS) and xylo
oligosaccharides (XOS) on gut morphology and hepatic oxidative status were
studied in European sea bass juveniles weighing 60 g. Fish were fed diets
including fishmeal (FM diets) or plant feedstuffs (PF diets; 30 FM:70 PF) as main
protein sources (control diets). Four other diets were formulated similar to the
control diets but including 1 % scFOS or 1 % XOS. At the end of the trial, fish
fed PF-based diets presented histomorphological alterations in the distal
intestine, whereas only transient alterations were observed in the pyloric caeca.
Comparatively to fish fed FM-based diets, fish fed PF diets had higher liver
lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT)
activities, and lower glutathione peroxidase, glutathione reductase and glucose 6
phosphate dehydrogenase activities. In fish fed the PF diets, prebiotic
supplementation decreased SOD activity and XOS supplementation further decreased
CAT activity. In fish fed the FM diets, XOS supplementation promoted a reduction
of all antioxidant enzyme activities. Overall, dietary XOS and scFOS
supplementation had only minor effects on gut morphology or LPO levels. However,
dietary XOS reduced antioxidant enzymatic activity in both PF and FM diets, which
indicate a positive effect on reduction of hepatic reactive oxygen species
production.
PMID- 26435351
TI - Implementing the Incident Command System into a Community Health System.
PMID- 26435352
TI - When Someone Dies in the Emergency Department: Perspectives of Emergency Nurses.
AB - Emergency nurses work in a clinical area where treatment measures usually are
provided quickly, and they have little time to establish relationships. In
addition to performing life-saving interventions, emergency nurses provide care
for patients who are dying. Little is known about the experiences of emergency
nurses who care for patients who die in the emergency department in the Canadian
context. METHODS: This study used a qualitative design with an interpretive
descriptive approach. Semistructured interviews were conducted with 11 ED nurses
from a large Canadian academic health sciences system. RESULTS: In-depth analysis
of the data resulted in 3 major themes: "It's not a nice place to die," "I see
the grief," and "Needing to know you've done your best." Findings revealed that
emergency nurses believed the environment made it difficult to care for dying
patients and their families because of unpredictability, busyness, noise, lack of
privacy, and the need to manage many patients simultaneously. These nurses were
also put in the position of caring for the suddenly bereaved family members,
which was viewed as an especially challenging aspect of their role. DISCUSSION:
Caring for adults who die in the emergency department is a difficult and
challenging aspect of the emergency nursing role. Emergency nurses believed they
did their best to provide end-of-life care interventions, which brought a sense
of professional satisfaction. Recommended future interventions include advocating
for ED design and physical layout to support compassionate end-of-life care,
provision of policies and training to support families and family presence, and
support of nursing staff.
PMID- 26435353
TI - Mental Status Changes--A Red Flag.
PMID- 26435354
TI - A Systematic Review of Evidence on the Use of Very Low Calorie Diets in People
with Diabetes.
AB - BACKGROUND: Recent interest has emerged regarding the effects of Very Low Calorie
Diet (VLCD) in people with type 2 diabetes (T2D). We therefore performed a
systematic review to investigate the effects of VLCD on HbA1c, weight and
cardiovascular risk profile outcomes as well as its safety and tolerability among
people with T2D. METHODS: We conducted searches of Cochrane Database of
Systematic Reviews, Centre for reviews and Dissemination databases, Medline,
Embase, Pubmed, Web of Science, Web of Knowledge and Turning Research into
Practice (TRIP) as well as ongoing trial resources. We included all studies
involving VLCD and diabetes published until December 2013. Outcome measures
include weight, HbA1c, fasting glucose, fasting insulin, lipid profile, blood
pressure, safety and drop out rates. RESULTS: 17 studies were included in the
systematic review. Duration of VLCD duration ranged from 5 days to 6 months and
duration of follow up ranged from 8 days to 5 years. The age range was 14 years
to 59 years of age. Mean weight loss was 13.2kg, ranging from 4.1 to 24kg. Mean
Hba1c reduction was 1.4% (ranging between 0.1 to 3.1% reduction across different
studies). Three studies reported a significant reduction in the daily doses of
insulin. All studies which reported cardiovascular risk profile showed a
significant decrease in total cholesterol, systolic and diastolic blood pressure
post VLCD. Apart from two studies, all of the other studies showed that the
decrease in blood pressure and total cholesterol was not only present immediately
post VLCD, but it was also maintained at follow up. However it is important to
note that the follow up periods did differ between studies. Overall, drop out
rates ranged from 4.7% to 33% and appeared to be lower during the active
intervention phase compared with during the follow-up period. No major adverse
event was reported apart from one study which recorded a non-fatal myocardial
infarction. CONCLUSION: This review demonstrated that VLCD in people with T2D was
associated with significant weight loss, reduction in blood glucose profile and
improvement in cardiovascular risk profile, high tolerability and good safety
outcomes. Studies were heterogeneous and longer term outcomes data post VLCD is
still required.
PMID- 26435355
TI - Persistence length of dendronized polymers: the self-consistent field theory.
AB - We present numerical results for the thermodynamic rigidity and induced
persistence length of dendronized polymers with systematically varied topology of
their grafts obtained by the Scheutjens-Fleer self-consistent field method. The
results were compared to predictions of an analytical mean-field theory. The two
approaches have marked different predictions. In particular, the analytical
theory predicts that the induced persistence length and the effective segment
aspect ratio of dendronized polymers are increasing functions of the degree of
branching of their side chains, whereas numerical calculations provide evidence
of the opposite dependences. This discrepancy is argued to be due to the ability
of side chains to repartition from the compressed to the dilated regions of a
curved bottle brush, which is accounted for by the numerical, but not by the
analytical method. The difference is most crucial in the light of the expected
ability of dendronized polymers to have a liquid crystalline ordering in semi
dilute solutions.
PMID- 26435356
TI - Policies to foster quality improvement registries: lessons from the Swedish case.
AB - BACKGROUND AND OBJECTIVES: Multi-institutional quality improvement registries (QI
registries) are a promising approach to quality improvement. They are also used
for clinical research, public quality reporting and other valuable purposes. The
aim of this study was to identify elements and outcomes of national policies to
promote registries in Sweden and to compare them with recent policies in the USA.
METHODS: This case study draws on previous studies of Swedish registries and on
interviews, observations and document studies conducted in Sweden and the USA.
RESULTS: In Sweden, registries are fostered by favourable patient data regulation
and an indirect control approach combining government funding with soft
regulation and professional self-governance. This enables the development of high
quality QI registries which are used for improvements by engaged clinicians, for
clinical research and for decision support for practitioners and stakeholders.
For example, Riks-HIA/Swedeheart achieved improved outcomes in cardiac intensive
care, SCAAR/Swedeheart was used in a unique registry-based randomized trial, and
the Swedish Rheumatology Quality Register provides a Web interface for patient
encounters and clarifies adverse effects of biologic drugs. Still, the system has
persistent limitations, especially the administrative burden on participants. In
the USA, Medicare's programme for qualified clinical data registries and other
recent changes mirror Swedish policies. Automated data capture is a US advantage,
but uncertain funding and complex data regulations stall registry development in
the USA. CONCLUSION: The findings of this study indicate that tailor-made data
regulation and a soft regulatory policy approach foster high-quality QI
registries with multiple meaningful uses. These findings offer a framework for
further cross-country comparative study to evaluate registry policies.
PMID- 26435357
TI - Complete hydrogen release from aqueous ammonia-borane over a platinum-loaded
titanium dioxide photocatalyst.
AB - Complete H2 release from ammonia-borane (NH3BH3, AB) in water was achieved by
using platinum-loaded TiO2 (Pt/TiO2) via two consecutive reaction steps, i.e.,
hydrolysis of AB and photocatalytic decomposition of thus formed NH3 in water,
under inert conditions at 298 K.
PMID- 26435358
TI - Natural inorganic nanoparticles--formation, fate, and toxicity in the
environment.
AB - The synthesis, stability, and toxicity of engineered metal nanoparticles (ENPs)
have been extensively studied during the past two decades. In contrast, research
on the formation, fate, and ecological effects of naturally-occurring
nanoparticles (NNPs) has become a focus of attention only recently. The natural
existence of metal nanoparticles and their oxides/sulfides in waters,
wastewaters, ore deposits, mining regions, and hydrothermal vents, as exemplified
by the formation of nanoparticles containing silver and gold (AgNPs and AuNPs),
Fe, Mn, pyrite (FeS2), Ag2S, CuS, CdS, and ZnS, is dictated largely by
environmental conditions (temperature, pH, oxic/anoxic, light, and concentration
and characteristics of natural organic matter (NOM)). Examples include the
formation of nanoparticles containing pyrite, Cu and Zn-containing pyrite, and
iron in hydrothermal vent black smoker emissions. Metal sulfide nanoparticles can
be formed directly from their precursor ions or indirectly by sulfide ion
assisted transformation of the corresponding metal oxides under anaerobic
conditions. This tutorial focuses on the formation mechanisms, fate, and toxicity
of natural metal nanoparticles. Natural waters containing Ag(I) and Au(III) ions
in the presence of NOM generate AgNPs and AuNPs under thermal, non-thermal, and
photochemical conditions. These processes are significantly accelerated by
existing redox species of iron (Fe(II)/Fe(III)). NOM, metal-NOM complexes, and
reactive oxygen species (ROS) such as O2(-), OH, and H2O2 are largely responsible
for the natural occurrence of nanoparticles. AgNPs and AuNPs emanating from
Ag(I)/Au(III)-NOM reactions are stable for several months, thus indicating their
potential to be transported over long distances from their point of origin.
However, endogenous cations present in natural waters can destabilize the
nanoparticles, with divalent cations (e.g., Ca(2+), Mg(2+)) being more
influential than their monovalent equivalents (e.g., Na(+), K(+)). The toxicity
of NNPs may differ from that of ENPs because of differences in the coatings on
the nanoparticle surfaces. An example of this phenomenon is presented and is
briefly discussed.
PMID- 26435359
TI - Development of the pancreas in medaka, Oryzias latipes, from embryo to adult.
AB - To address conserved and unique features of fish pancreas development, we
performed extensive analyses of pancreatic development in medaka embryos and
adults using pdx1- and ptf1a-transgenic medaka, in situ hybridization and
immunohistochemistry. The markers used in these analyses included pdx1, nkx6.1,
nkx6.2, nkx2.2, Islet1, insulin, Somatostatin, glucagon, ptf1a, ela3l, trypsin,
and amylase. The double transgenic (Tg) fish produced in the present study
visualizes the development of endocrine (pdx1+) and exocrine (ptf1a+) parts
simultaneously in living fishes. Like other vertebrates, the medaka pancreas
develops as two (dorsal and ventral) buds in the anterior gut tube, which soon
fuse into a single anlagen. The double Tg fish demonstrates that the differential
property between the two buds is already established at the initial phase of bud
development as indicated by strong pdx1 expression in the dorsal one. This Tg
fish also allowed us to examine the gross morphology and the structure of adult
pancreas and revealed unique characters of medaka pancreas such as broad and
multiple connections with the gut tube along the anterior-posterior axis.
PMID- 26435360
TI - Local co-delivery of rhBMP-2 and cathepsin K inhibitor L006235 in poly(d,l
lactide-co-glycolide) nanospheres.
AB - Cathepsin K inhibitors (CKIs) are an emerging class of drugs that are potent
antagonists of osteoclastic activity. We speculated that they may be beneficial
in bone tissue engineering, where a stress shielded environment can lead to rapid
resorption of new bone. Most CKIs require frequent dosing, so to achieve a
sustained release we manufactured polymer nanoparticles encapsulating the CKI
L006235 (CKI/nP). CKI/nP and the collagen matrices that were used to deliver them
were characterized by electron microscopy and fluorescent confocal microscopy,
and data indicated that the particles were evenly distributed throughout the
collagen. Elution studies indicated a linear release of the inhibitor from the
CKI/nP, with approximately 2% of the drug being released per day. In an in vivo
study, mice were implanted with collagen scaffolds containing rhBMP-2 that were
loaded with the CKI/nP. Measurement of bone volume (BV) by microCT showed no
significant increase with CKI/nP incorporation, and other parameters similarly
showed no statistical differences. Cell culture studies confirmed the activity of
the drug, even at low concentrations. These data indicate that polymer
nanoparticles are an effective method for sustained drug delivery of a CKI,
however, this may not be readily translatable to substantively improved bone
tissue engineering outcomes. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res
Part B: Appl Biomater, 105B: 136-144, 2017.
PMID- 26435361
TI - Steroidogenesis by testis and accessory glands of the Lusitanian toadfish,
Halobatrachus didactylus, during reproductive season.
AB - In teleost fish sex steroids are essential for gonadal function and have marked
effects in reproductive and agonistic behavior and in the expression of secondary
sexual characteristics. The Lusitanian toadfish, Halobatrachus didactylus, has
two male morphotypes: type I males are territorial nest-holders and have large
accessory glands while type II males are smaller, have a relatively large testis
and small accessory glands. In the present study, the steroidogenic activity of
the testis and accessory testicular glands of the Lusitanian toadfish were
examined in vitro as well as their presence in urine. The testis of type I males
produced 11-ketotestosterone (11KT) and 11beta-hydroxy-4-androstene-3,17-dione
(11betaA) from tritiated 17-hydroxyprogesterone, while those of type II males
produced testosterone (T) and 11beta,17beta-dihydroxy-4-andosten-3-one (11betaT),
but not 11KT. Additionally, the testis and accessory glands of both morphs
produced mostly 5beta,3alpha-reduced and 17,20alpha-hydroxylated metabolites.
Type I, but not of type II, males synthesised 5beta-reduced androgens in their
accessory glands. The presence of 11betaA exclusively in the urine of type I
males during reproductive season suggests an association with maintenance of
secondary sexual characteristics and behavior in this morph. The urine of both
types of males contained two 5alpha-androstane and 5beta-pregnane glucuronides.
Among the latter steroids, those that are 17,21-dihydroxylated are potentially
metabolites from cortisol and were found only in type I males during the spawning
season. The diversity of metabolites produced by the testis and accessory glands
and the presence of some in urine is suggestive of a potential role in chemical
communication and reproductive behavior.
PMID- 26435362
TI - Controlled generation of highly saddled (porphyrinato)iron(III) iodide, tri
iodide and one-electron oxidized complexes.
AB - For the first time, three iron(III) porphyrinato complexes have been synthesized
selectively by varying the iodine concentration in the reaction mixture which
eventually forms both five and six coordinate complexes with iodide and/or tri
iodide as axial ligands. Combined analysis using single crystal X-ray structure
determination, and Mossbauer, (1)H NMR and EPR studies as well as VT magnetic
studies has revealed the admixed-intermediate (iodo complex), pure intermediate
(tri-iodide complex) and high-spin (1e-oxidized complex) states of iron.
PMID- 26435364
TI - Influence of dose reduction of vincristine in R-CHOP on outcomes of diffuse large
B cell lymphoma.
AB - Dose intensity (DI) of chemotherapy affects prognosis of diffuse large B cell
lymphoma (DLBCL). Myelotoxicity is the major dose-limiting toxicity (DLT) of most
cytotoxic agents for hematological malignancies, whereas DLT of vincristine (VCR)
is mainly neurological toxicity. Although VCR is a key drug and its combination
with other cytotoxic agents needs consideration, studies focused on relative DI
(RDI) of VCR have not been done before. We retrospectively analyzed 86 cases of
DLBCL that received six or more cycles of cyclophosphamide (CPM), doxorubicin
(DXR), VCR, prednisolone, and rituximab [R-CHOP] and calculated RDI of each
cytotoxic agent to analyze its influence on treatment outcome. The median RDI of
CPM, doxorubicin, and VCR was 80.0, 81.7, and 78.4 %, respectively (p = 0.002).
The average RDI (ARDI) of these three agents was 80.0 %. The overall survival was
significantly worse in the low ARDI (<85 %) than in the high ARDI (>85 %) group
(2-year survival rate 67.2 vs 93.4 %, p = 0.011). The survival rate with low RDI
VCR (<85 %) was lower than that with high RDI VCR (>85 %), even when the
remaining two agents had high ARDI (2-year survival rate 74.3 vs 95.8 %, p =
0.047). In conclusion, VCR dose tended to be reduced compared with CPM and DXR in
R-CHOP. Lower ARDI of cytotoxic agents and lower RDI of VCR could lead to poor
prognosis in the treatment of DLBCL with R-CHOP. We thought these observations
should be confirmed in a prospective study.
PMID- 26435363
TI - Daylight photodynamic therapy with methyl aminolevulinate cream is effective and
nearly painless in treating actinic keratoses: a randomised, investigator
blinded, controlled, phase III study throughout Europe.
AB - BACKGROUND: Unmet needs exist in actinic keratosis (AK) treatment. Daylight
photodynamic therapy (DL-PDT) has shown good efficacy and safety results compared
to conventional PDT (c-PDT) in a recent Phase III multi-centre randomised
controlled trial in Australia among 100 subjects with AKs. OBJECTIVES:
Demonstrate non-inferior efficacy and superior safety of DL-PDT compared to c-PDT
in treating multiple mild and/or moderate facial/scalp AKs. METHODS: Phase III,
12 week, multi-centre, randomised, investigator-blinded, controlled, intra
individual study conducted at different latitudes in Europe. AKs of adult
subjects were treated once with methyl aminolevulinate (MAL) DL-PDT on one side
of the face and MAL c-PDT contralaterally. Endpoints for DL-PDT concerned
efficacy (non-inferiority regarding complete lesion response at week 12) and
safety (superiority regarding subject's assessment of pain after treatment, on an
11-point numeric rating scale). Safety evaluation also included incidence of
adverse events. Subject satisfaction was described using a questionnaire at
baseline and last visit. RESULTS: At week 12, the total lesion complete response
rate with DL-PDT was similar (non-inferior) to c-PDT (70% vs. 74%, respectively;
95% CI [-9.5; 2.4] in PP analysis, confirmed in ITT analysis). In addition,
efficacy of DL-PDT was demonstrated regardless of weather conditions (sunny or
cloudy). DL-PDT was nearly painless compared to c-PDT (0.7 vs. 4.4, respectively;
P < 0.001), better tolerated and resulted in higher subject satisfaction.
CONCLUSION: DL-PDT in comparison with c-PDT was as effective, better tolerated
and nearly painless with high patient satisfaction, and may be considered a
treatment of choice to meet needs of patients with mild or moderate facial/scalp
AKs.
PMID- 26435366
TI - [Delayed Brain Injury after Aneurysmal Subarachnoid Hemorrhage:Update and
Perspective].
PMID- 26435365
TI - Twice-daily insulin degludec/insulin aspart provides superior fasting plasma
glucose control and a reduced rate of hypoglycaemia compared with biphasic
insulin aspart 30 in insulin-naive adults with Type 2 diabetes.
AB - AIM: To evaluate the efficacy and safety of twice-daily insulin degludec/insulin
aspart vs. twice-daily biphasic insulin aspart 30 in people with Type 2 diabetes
mellitus who were naive to insulin. METHODS: In this 26-week, multinational, open
label, controlled, two-arm, parallel-group, treat-to-target trial, participants
[mean (+/- sd) age 58.9 (+/-8.9) years, duration of diabetes 9.5 (+/-5.9) years,
HbA1c 68 (+/-8.7) mmol/mol or 8.4 (+/-0.8)% and BMI 31.2 (+/-4.2) kg/m(2) ) were
randomized (1:1) to insulin degludec/insulin aspart (n = 197) or biphasic insulin
aspart 30 (n = 197), administered with breakfast and the main evening meal,
titrated to a self-monitored plasma glucose target > 3.9 and <= 5.0 mmol/l.
RESULTS: The mean HbA1c was reduced to 49 mmol/mol (6.6%) with insulin
degludec/insulin aspart and 48 mmol/mol (6.5%) with biphasic insulin aspart 30.
Insulin degludec/insulin aspart achieved the prespecified non-inferiority margin
(estimated treatment difference 0.02%; 95% CI -0.12, 0.17). Insulin
degludec/insulin aspart was superior in lowering fasting plasma glucose
(estimated treatment difference -1.00 mmol/l; 95% CI -1.4, -0.6; P < 0.001) and
reducing overall and nocturnal confirmed hypoglycaemia at a similar overall
insulin dose compared with biphasic insulin aspart 30. Similar proportions of
participants in each arm experienced severe hypoglycaemia. Adverse events were
equally distributed. CONCLUSIONS: Consistent with previous findings, insulin
degludec/insulin aspart twice daily effectively improved long-term glycaemic
control, with superior reductions in FPG, and significantly less overall and
nocturnal confirmed hypoglycaemia compared with biphasic insulin aspart 30 in
people with Type 2 diabetes who were insulin-naive.
PMID- 26435367
TI - [Traumatic Brain Injury Data Bank].
PMID- 26435368
TI - [Effects of Endovascular Treatment on Cranial Nerve Palsy due to Unruptured
Intracranial Aneurysms].
AB - This study aimed to assess the effects of endovascular treatment on cranial nerve
palsy due to unruptured intracranial aneurysms. Endovascular coiling was
performed in 203 patients with intracranial aneurysms between April 2002 and
March 2012 in our hospital. Of these patients, 8(3.9%)presented with cranial
nerve palsy due to unruptured intracranial aneurysms. Cranial nerve palsy
involved the oculomotor nerve in 8 patients and the optic nerve in 2 patients.
Two patients had both optic nerve and oculomotor nerve dysfunction. Patients with
incomplete oculomotor nerve palsy at admission were more likely to have full
recovery after coiling. Optic nerve dysfunction did not improve after coiling.
Incomplete oculomotor nerve palsy, early treatment(<=15 days), and small
aneurysms(<=10 mm)were likely to be associated with complete recovery after
coiling. This study indicates that endovascular coiling may resolve cranial nerve
palsy due to unruptured intracranial aneurysms in patients who have incomplete
oculomotor nerve palsy due to small aneurysms and are treated as early as
possible after symptom onset.
PMID- 26435369
TI - [Clinical Study on Cerebellar Contusion:A Report on 9 Cases and Literature
Review].
AB - We report 9 cases of cerebellar contusion from April 2011 to September 2014 at
our department. Frequency, clinicoradiological findings, mechanism of injury,
treatments, and outcomes were retrospectively analyzed. Of 239 head injury cases
admitted to our department during the same period, 9(3.8%)were diagnosed as
cerebellar contusion. Among these 9 cases, 7 were men, and 2 were women. The
patient age ranged from 12 to 83 years with a mean age of 64.7 years. The
mechanism of injury was traffic accident in one patient, and fall in 8. All cases
were associated with direct head trauma to the occiput, and radiographic studies
showed occipital bone fracture in 8 cases. Six cases were managed conservatively.
Three cases underwent suboccipital craniectomies and clot evacuations. Glasgow
Outcome Scale(GOS)score at discharge were Good Recovery(GR)in 2, Moderate
Disability(MD)in 2, Severe Disability(SD)in 3, Vegetative State(VS)in 1, and
Dead(D)in 1. GOS scores in surgically treated cases were GR in 1, SD in 1, and VS
in 1. Supratentorial severe traumatic lesions were concomitant with poor
prognosis. Coup injury was a significant cause of cerebellar contusion. External
decompression and clot evacuation were useful in patients who suffered severe
cerebellar contusion;however, concomitant supratentorial lesions influenced the
prognosis.
PMID- 26435370
TI - [Application of Silicone Rubber Stents in Intracranial Arterial Microanastomosis
for Vessels with Intimal Dissection:A Technical Note].
AB - Intracranial arterial microanastomosis remains an important neurosurgical
technique. Intimal dissection of donor or recipient arteries can cause bypass
failure. We used a silicone rubber stent while performing arterial
microanastomoses, and achieved an excellent postoperative patency rate. In this
study, we evaluated the efficacy of the stent in cases of extensive intimal
dissection. In 5 cases involving extensive intimal dissection of vessels out of a
total of 856 microanastomoses that were performed between November 2000 and
August 2014, we placed a silicone rubber stent in the lumen of the recipient
artery for donor to recipient suturing. Surgery was performed in 3 cases of
cerebrovascular atherosclerotic disease and in 2 cases requiring cerebral
revascularization for the treatment of aneurysm recurrence. In one of the 5 cases
in which arterial microanastomosis was performed in the spasm period after
subarachnoid hemorrhage, a patent anastomosis could not be confirmed. We observed
the following advantages of silicone stent use: clear visualization of the
orifice created in the vessel, avoidance of suturing or damaging the
contralateral side vessel edges, and maintenance of the shape of the anastomosed
vessel segment. These advantages made it easier to visualize the intima and to
achieve fixation by using tacking sutures.
PMID- 26435371
TI - [Usefulness of a Transbrachial Guide Sheath Specifically Designed for Direct
Common Carotid Artery Cannulation in Common Carotid Artery Stenting].
AB - The transfemoral approach is a common technique for carotid artery
stenting(CAS)and involves the risk of distal embolism when a high-grade stenosis
occurs at the common carotid artery(CCA). In this study, to minimize the risk of
thromboembolic complications, we used a guide sheath that was specifically
designed for direct cannulation to the CCA without the use of a guidewire or
coaxial catheter. This study included 5 patients who underwent CAS of the CCA by
using a guide sheath. Of these patients, 2 had right CCA stenosis and the other 3
had left CCA lesions. In all cases, direct cannulation to the target CCA by using
the guide sheath was achieved, and CAS was performed safely. The median time from
puncture to the end of the procedure was 61 min(interquartile range: 53-63). No
periprocedural complications or cardiovascular events occurred within 30 days
after CAS. CAS was safely and successfully performed for CCA stenosis by using
the transbrachial guide sheath that was specifically designed for direct
cannulation to the CCA.
PMID- 26435372
TI - [A Case of Transorbital Penetrating Brain Injury Caused by a Steel Wire Entirely
Embedded in the Brain Parenchyma].
AB - Penetrating brain injury(PBI)is very rare in Japan. Because there is a very wide
variety of pathological condition of PBI, the guideline for the treatment of PBI
has not been established yet. We report the unique case of PBI caused by a steel
wire piece completely embedded in the brain parenchyma. A 75-year-old man was
brought to the emergency department due to ocular injury caused by a steel wire
piece. Neurological examination revealed only left visual disturbance. CT scan
revealed a steel wire piece located intraparenchymally between the left frontal
lobe and the ventricles, but digital subtraction angiography showed no
significant vascular injury in the surrounding structures. We performed an open
surgery and removed the steel wire piece. Because the steel wire piece was
completely embedded in the brain, we used intraoperative X-ray fluoroscopy to
choose a less invasive approach for the brain. The patient suffered no additional
neurological deficit and no sign of cerebral infection or seizure after surgery.
He was discharged after a 4-week administration of antibiotics. In most cases of
PBI caused by low velocity injury, foreign bodies are not completely embedded in
the brain except for remnants after surgical removal. This is the first report of
low velocity PBI caused by a foreign body completely embedded in the brain.
PMID- 26435373
TI - [Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case
Reports].
AB - Metronidazole is a widely used antibiotic against anaerobic bacteria and
protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during
treatment of a brain abscess with metronidazole. The patients developed mental
disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case
1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We
initiated treatment with oral metronidazole. After taking the medication, she
developed mental disturbance, and her brain MRI showed a hyperintensity within
the corpus callosum. We suspected metronidazole toxicity and discontinued
metronidazole treatment. The symptoms resolved rapidly within a week, and the
hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to
our hospital with a brain abscess. We initiated treatment with oral
metronidazole. On day 38, he developed mental disturbance, and his MRI showed
hyperintensities within the bilateral dentate nuclei and corpus callosum. These
symptoms were consistent with MIE. After cessation of metronidazole, his symptoms
and abnormal MRI signals completely disappeared.
PMID- 26435374
TI - [A Single-Stage Combined Supra- and Infra-Sellar Approach for Recurrent Large
Pituitary Adenomas:Report of Two Cases].
AB - Despite the recent technological advances in operative instruments and
development of novel techniques for endoscopic skull-base surgeries, surgical
treatment of primary or recurrent large/giant pituitary adenomas remains a
challenge. Postoperative hemorrhage from the residual tumor and the associated
impairment of the adjacent cranial nerve functions can cause severe morbidity. To
manage such operative risks, a combined supra- and infra-sellar
approach(CSISA)can be used as a surgical option for difficult-to-resect
large/giant pituitary adenomas. We successfully performed a single-stage CSISA in
two patients with large recurrent pituitary adenomas with favorable outcomes.
Both patients had recurrent adenomas after multiple trans-sphenoidal surgeries
and presented with visual impairment due to tumor regrowth. Each tumor had a
maximum diameter of more than 4 cm. One tumor extended into the anterior skull
base, while the other extended into the supra-sellar region with extremely
lateral invasion. The CSISA helped surgeons visualize the tumors and the
surrounding structures through a combination of different operative views.
Subtotal resection was safely achieved in both cases, with no postoperative
hemorrhage and deterioration of visual and pituitary function. The CSISA is
useful not only for pituitary adenomas with anterior or lateral extension and
multi-lobular growth, but also for certain cases with recurrent large/giant
pituitary adenomas.
PMID- 26435375
TI - Factors associated with failure to achieve a glycated haemoglobin target of <8.0%
in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
AB - The aim of this study was to identify the clinical features of participants in
the standard therapy arm of the Action to Control Cardiovascular Risk in Diabetes
(ACCORD) glycaemia trial who failed to reach the glycated haemoglobin (HbA1c)
target. We analysed 4685 participants in the standard therapy arm, comparing
participants who reached the HbA1c target of <8.0% with those whose HbA1c level
was >=8.0% 12 months after randomization. Baseline and 12-month clinical
characteristics were compared. At 12 months after randomization, 3194
participants had HbA1c <8.0% and 1491 had HbA1c >=8.0%. Black race [odds ratio
(OR) 0.74, 95% confidence interval (CI) 0.61-0.89; p = 0.002], severe
hypoglycaemia (OR 0.57, CI 0.37-0.89; p = 0.014) and insulin use (OR 0.51, CI
0.40-0.65; p < 0.001) were associated with failure to reach HbA1c goal at 12
months in the adjusted model. Even with free medications, free visits with
clinicians and aggressive titration of medications, >30% of participants in the
standard arm of the ACCORD trial had an HbA1c >=8.0% at 1 year. Participants who
were black, had severe hypoglycaemia and were on insulin were more likely to have
an above-target HbA1c concentration after 12 months on the standard protocol.
PMID- 26435376
TI - Spontaneous Formation of RNA Strands, Peptidyl RNA, and Cofactors.
AB - How the biochemical machinery evolved from simple precursors is an open question.
Here we show that ribonucleotides and amino acids condense to peptidyl RNAs in
the absence of enzymes under conditions established for genetic copying.
Untemplated formation of RNA strands that can encode genetic information,
formation of peptidyl chains linked to RNA, and formation of the cofactors
NAD(+), FAD, and ATP all occur under the same conditions. In the peptidyl RNAs,
the peptide chains are phosphoramidate-linked to a ribonucleotide. Peptidyl RNAs
with long peptide chains were selected from an initial pool when a lipophilic
phase simulating the interior of membranes was offered, and free peptides were
released upon acidification. Our results show that key molecules of genetics,
catalysis, and metabolism can emerge under the same conditions, without a mineral
surface, without an enzyme, and without the need for chemical pre-activation.
PMID- 26435377
TI - Transannular [6 + 4] and Ambimodal Cycloaddition in the Biosynthesis of
Heronamide A.
AB - The transannular [6 + 4] cycloaddition proposed as a step in the biosynthesis of
heronamide A has been modeled using density functional theory. The proposed
cycloaddition is highly stereoselective, affording a single product. The reaction
proceeds through an ambimodal transition state that directly leads to a [4 + 2]
adduct in addition to the observed [6 + 4] adduct. Interconversion of these
adducts is possible via a facile Cope rearrangement. The [6 + 4] adduct is
thermodynamically more stable than the [4 + 2] adduct by 5.2 kcal mol(-1) due to
a combination of the ring and steric strain in the [4 + 2] product. The results
strongly support the plausibility of the proposed transannular [6 + 4]
cycloaddition in the biogenesis of heronamide A and may provide insights to
designing substrates that selectively undergo [6 + 4] cycloaddition to form
unbridged 10-membered rings.
PMID- 26435378
TI - Microscopic haematuria at time of diagnosis is associated with lower disease
stage in patients with newly diagnosed bladder cancer.
AB - OBJECTIVES: To determine whether the severity of haematuria (microscopic or
gross) at diagnosis influences the disease stage at presentation in patients
diagnosed with bladder cancer. PATIENTS AND METHODS: We conducted a multi
institutional observational cohort study of patients who were newly diagnosed
with bladder cancer between August 1999 and May 2012. We reviewed the degree of
haematuria, demographic information, clinical and social history, imaging, and
pathology. The association of haematuria severity with incident tumour stage and
grade was evaluated using logistic regression. RESULTS: Patients diagnosed with
bladder cancer presented with gross haematuria (GH; 1 083, 78.3%), microscopic
haematuria (MH; 189, 13.7%) or without haematuria (112, 8.1%). High-grade disease
was found in 64% and 57.1% of patients presenting with GH and MH, respectively,
and severity of haematuria was not associated with higher grade disease. Stage of
disease at diagnosis for patients presenting with MH was Ta/carcinoma in situ
(CIS) in 68.8%, T1 in 19.6%, and >=T2 in 11.6%. Stage of disease at diagnosis for
patients presenting with GH was Ta/CIS in 55.9%, T1 in 19.6%, and >=T2 in 17.9%.
On multivariate analyses, GH was independently associated with >=T2 disease at
diagnosis (odds ratio 1.69, 95% confidence interval 1.05-2.71, P = 0.03).
CONCLUSIONS: Among patients with newly diagnosed bladder cancer, presentation
with GH is associated with a more advanced pathological stage. Earlier detection
of disease, before development of GH, could influence survival in patients with
bladder cancer. Type of haematuria at presentation does not impact grade of
disease.
PMID- 26435379
TI - Prediction of Blood Pressure and Blood Pressure Change With a Genetic Risk Score.
AB - The authors investigated whether a genetic risk score (GRS) constructed of 32
single nucleotide polymorphisms would predict incident hypertension and blood
pressure (BP) change over time in a population cohort during an 11-year follow-up
(n=5402 at baseline, 3266 at follow-up). In multivariable models, GRS was
associated with higher systolic/diastolic BP values at baseline (beta+/-standard
error [SE], 1.04+/-0.14/1.11+/-0.13 mm Hg; P<.0001 for both) and at
reinvestigation (beta+/-SE, 0.84+/-0.18/0.79+/-0.16 mm Hg; P<.0001 for both).
Among participants who were normotensive at baseline (n=2045), GRS was not
independently associated with systolic/diastolic BP change over time (beta+/-SE,
0.16+/-0.18/0.20+/-0.18 mm Hg; P>=.28 for both). In participants in the top
tertile of the GRS, as compared with the bottom tertile, the predicted increase
in systolic/diastolic BP was 1.18+/-0.78/0.70+/-0.49 mm Hg (P=.046/.15) greater
and the odds ratio for incident hypertension was 33% higher (P=.03). These data
show that GRS is strongly associated with BP but weakly associated with BP
increase and incident hypertension in a late middle-aged population.
PMID- 26435380
TI - Clearance from the mouse brain by convection of interstitial fluid towards the
ventricular system.
AB - BACKGROUND: In the absence of a true lymphatic system in the brain parenchyma,
alternative clearance pathways for excess fluid and waste products have been
proposed. Suggested mechanisms for clearance implicate a role for brain
interstitial and cerebrospinal fluids. However, the proposed direction of flow,
the anatomical structures involved, and the driving forces are controversial.
METHODS: To trace the distribution of interstitial and cerebrospinal fluid in the
brain, and to identify the anatomical structures involved, we infused a mix of
fluorescent tracers with different sizes into the cisterna magna or striatum of
mouse brains. We subsequently performed confocal fluorescence imaging of
horizontal brain sections and made 3D reconstructions of the mouse brain and
vasculature. RESULTS: We observed a distribution pattern of tracers from the
parenchyma to the ventricular system, from where tracers mixed with the
cerebrospinal fluid, reached the subarachnoid space, and left the brain via the
cribriform plate and the nose. Tracers also entered paravascular spaces around
arteries both after injection in the cisterna magna and striatum, but this
appeared to be of minor importance. CONCLUSION: These data suggest a bulk flow of
interstitial fluid from the striatum towards the adjacent lateral ventricle.
Tracers may enter arterial paravascular spaces from two sides, both through bulk
flow from the parenchyma and through mixing of CSF in the subarachnoid space.
Disturbances in this transport pathway could influence the drainage of amyloid
beta and other waste products, which may be relevant for the pathophysiology of
Alzheimer's disease.
PMID- 26435381
TI - Malignancies in bullous pemphigoid: A controversial association.
AB - Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder that
has been reported to be associated with malignancies. Some authors described
several cases of pemphigoid associated with malignancies (PAM); however, the
evidence of this correlation still remains controversial. Several theories have
been postulated to explain the relationship between malignant neoplasms and BP;
the main theory suggests that antibodies directed against tumor-specific antigens
of malignant cells may cross-react with antigens (like BP antigens) in the
basement membrane zone leading to the formation of blisters. We performed an
extensive review of the English published work focusing on the epidemiology, the
pathogenetic theories and the clinical and histological aspects of the disease.
We identified 40 cases of PAM: of these, seven cases were associated with
hematological malignancies and 33 with solid tumors. Physicians should be aware
of the existence of PAM and we suggest an oncological screening in early-onset
pemphigoid, in patients with a former oncological history, in those with signs
and symptoms that could be related to a neoplasm and in BP refractory to common
immunosuppressive therapy.
PMID- 26435382
TI - Therapeutic Targeting of microRNAs in Cancer: Future Perspectives.
AB - Preclinical Research The discovery of microRNAs (miRNAs) and their link with
cancer has opened a new era in cancer therapeutics. Approximately, 18 - 24
nucleotides long, miRNAs can up-regulate or down-regulate gene expression in many
cancer types and are respectively categorized as oncogenes (oncomirs) or tumor
suppressors. Expression profiles of miRNAs with biomarker potential can be used
for the classification, diagnosis, therapeutic treatment, and prognosis of
different cancer types. miRNA mimics and miRNA antagonists are the two main
approaches to miRNA-based cancer therapies that respectively inhibit oncomirs or
restore the expression of tumor suppressive miRNAs. This review serves to provide
some general insight into miRNA biogenesis, cancer related miRNAs, and miRNA
therapeutics.
PMID- 26435383
TI - Predicting the future relapse of alcohol-dependent patients from structural and
functional brain images.
AB - In alcohol dependence, individual prediction of treatment outcome based on
neuroimaging endophenotypes can help to tailor individual therapeutic offers to
patients depending on their relapse risk. We built a prediction model for
prospective relapse of alcohol-dependent patients that combines structural and
functional brain images derived from an experiment in which 46 subjects were
exposed to alcohol-related cues. The patient group had been subdivided post hoc
regarding relapse behavior defined as a consumption of more than 60 g alcohol for
male or more than 40 g alcohol for female patients on one occasion during the 3
month assessment period (16 abstainers and 30 relapsers). Naive Bayes, support
vector machines and learning vector quantization were used to infer prediction
models for relapse based on the mean and maximum values of gray matter volume and
brain responses on alcohol-related cues within a priori defined regions of
interest. Model performance was estimated by leave-one-out cross-validation.
Learning vector quantization yielded the model with the highest balanced accuracy
(79.4 percent, p < 0.0001; 90 percent sensitivity, 68.8 percent specificity). The
most informative individual predictors were functional brain activation features
in the right and left ventral tegmental areas and the right ventral striatum, as
well as gray matter volume features in left orbitofrontal cortex and right medial
prefrontal cortex. In contrast, the best pure clinical model reached only chance
level accuracy (61.3 percent). Our results indicate that an individual prediction
of future relapse from imaging measurement outperforms prediction from clinical
measurements. The approach may help to target specific interventions at different
risk groups.
PMID- 26435384
TI - Imidazole tailored deep eutectic solvents for CO2 capture enhanced by hydrogen
bonds.
AB - Deep eutectic solvents (DESs) have emerged as promising alternative candidates
for CO2 capture in recent years. In this work, several novel DESs were firstly
prepared to enhance CO2 absorption. Structural and physical properties of DESs
were investigated, as well as their absorption performance of CO2. A distinct
depression in the melting point up to 80 K of DESs was observed compared with
that of BMIMCl. The observed red shifts of the C2H group in an imidazolium ring
and its chemical shifts downfield in NMR spectra are indicative of a hydrogen
bond interaction between BMIMCl and MEA. In particular, CO2 uptake in MEA : ILs
(4 : 1) at room temperature and atmospheric pressure is up to 21.4 wt%, which is
higher than that of 30 wt% MEA (13%). A hydrogen bond related mechanism was
proposed in which ILs act as a medium to improve CO2 uptake through hydrogen
bonds. Finally, the firstly reported overall heat of CO2 absorption is slightly
higher than that of 30 wt% MEA, implying that the hydrogen bonds of DESs
contribute to the overall heat of CO2 absorption. This study reveals that the
heat of CO2 absorption can be tailored by the proper molar ratio of MEA and ILs.
PMID- 26435385
TI - Multicomponent T2 analysis of articular cartilage with synovial fluid partial
volume correction.
AB - PURPOSE: To investigate the use of a three-pool model to account for the
confounding effects of synovial fluid on multicomponent T2 analysis of articular
cartilage using Multicomponent Driven Equilibrium Single Shot Observation of T1
and T2 (mcDESPOT). MATERIALS AND METHODS: mcDESPOT was performed on the knee of
eight asymptomatic volunteers and eight patients with osteoarthritis at 3.0T with
multicomponent T2 maps created using the two-pool model and a three-pool model
containing a nonexchanging synovial fluid water pool. The fraction of the fast
relaxing water component (FF ) and the T2 relaxation times for the fast-relaxing
(T2F ) and slow-relaxing (T2S ) water components were measured in the superficial
and deep layers of patellar cartilage using the two-pool and three-pool models in
asymptomatic volunteers and patients with osteoarthritis and were compared using
Wilcoxon signed rank tests. RESULTS: Within the superficial layer of patellar
cartilage, FF was 22.5% and 25.6% for asymptomatic volunteers and 21.3% and 22.8%
for patients with osteoarthritis when using the two-pool and three-pool models,
respectively, while T2S was 73.9 msec and 62.0 msec for asymptomatic volunteers
and 72.0 msec and 63.1 msec for patients with osteoarthritis when using the two
pool and three-pool models, respectively. For both asymptomatic volunteers and
patients with osteoarthritis, the two-pool model provided significantly (P <
0.05) lower FF and higher T2S than the three-pool model, likely due to the
effects of synovial fluid partial volume averaging. CONCLUSION: The effects of
partial volume averaging between superficial cartilage and synovial fluid may
result in biased multicomponent T2 measurements that can be corrected using an
mcDESPOT three-pool model containing a nonexchanging synovial fluid water pool.
PMID- 26435387
TI - Response of authors to Ganju and Dias' comments on 'Inclusion of Placebos and
Blinding for Ascending Dose First-in-Human Studies and Other Underpowered Phase 1
Studies Has Not Been Justified and on Balance is Not Useful' by D. A.
Parasrampuria and L. Z. Benet.
PMID- 26435386
TI - Endometriosis diagnosis and staging by operating surgeon and expert review using
multiple diagnostic tools: an inter-rater agreement study.
AB - OBJECTIVE: To determine agreement on endometriosis diagnosis between real-time
laparoscopy and subsequent expert review of digital images, operative reports,
magnetic resonance imaging (MRI), and histopathology, viewed sequentially.
DESIGN: Inter-rater agreement study. SETTING: Five urban surgical centres.
POPULATION: Women, aged 18-44 years, who underwent a laparoscopy regardless of
clinical indication. A random sample of 105 women with and 43 women without a
postoperative endometriosis diagnosis was obtained from the ENDO study. METHODS:
Laparoscopies were diagnosed, digitally recorded, and reassessed. MAIN OUTCOME
MEASURES: Inter-observer agreement of endometriosis diagnosis and staging
according to the revised American Society for Reproductive Medicine criteria.
Prevalence and bias-adjusted kappa values (kappa) were calculated for diagnosis,
and weighted kappa values were calculated for staging. RESULTS: Surgeons and
expert reviewers had substantial agreement on diagnosis and staging after viewing
digital images (n = 148; mean kappa = 0.67, range 0.61-0.69; mean kappa = 0.64,
range 0.53-0.78, respectively) and after additionally viewing operative reports
(n = 148; mean kappa = 0.88, range 0.85-0.89; mean kappa = 0.85, range 0.84-0.86,
respectively). Although additionally viewing MRI findings (n = 36) did not
greatly impact agreement, agreement substantially decreased after viewing
histological findings (n = 67), with expert reviewers changing their assessment
from a positive to a negative diagnosis in up to 20% of cases. CONCLUSION:
Although these findings suggest that misclassification bias in the diagnosis or
staging of endometriosis via visualised disease is minimal, they should alert
gynaecologists who review operative images in order to make decisions on
endometriosis treatment that operative reports/drawings and histopathology, but
not necessarily MRI, will improve their ability to make sound judgments.
TWEETABLE ABSTRACT: Endometriosis diagnosis and staging agreement between expert
reviewers and operating surgeons was substantial.
PMID- 26435388
TI - Utility of heme analogues to intentionally modify heme-globin interactions in
myoglobin.
AB - Myoglobin reconstitution with various synthetic heme analogues was reviewed to
follow the consequences of modified heme-globin interactions. Utility of dimethyl
sulfoxide as the solvent for water-insoluble hemes was emphasized. Proton NMR
spectroscopy revealed that loose heme-globin contacts in the heme pocket
eventually caused the dynamic heme rotation around the iron-histidine bond. The
full rotational rate was estimated to be about 1400 s(-1) at room temperature for
1,4,5,8-tetramethylhemin. The X-ray analysis of the myoglobin containing iron
porphine, the smallest heme without any side chains, showed that the original
globin fold was well conserved despite the serious disruption of native heme
globin contacts. Comparison between the two myoglobins with static and rotatory
prosthetic groups indicated that the oxygen and carbon monoxide binding profiles
were almost unaffected by the heme motion. On the other hand, altered
tetrapyrrole array of porphyrin dramatically changed the dissociation constant of
oxygen from 0.0005 mm Hg of porphycene-myoglobin to infinity in oxypyriporphyrin
myoglobin. Heme-globin interactions in myoglobin were also monitored with
circular dichroism spectroscopy. The observation on several reconstituted protein
revealed an unrecognized role of the propionate groups in protoheme. Shortening
of heme 6,7-propionates to carboxylates resulted in almost complete disappearance
of the positive circular dichroism band in the Soret region. The theoretical
analysis suggested that the disappeared circular dichroism band reflected the
cancellation effects between different conformers of the carboxyl groups directly
attached to heme periphery. The above techniques were proposed to be applicable
to other hemoproteins to create new biocatalysts. This article is part of a
Special Issue entitled Biodesign for Bioenergetics--the design and engineering of
electronic transfer cofactors, proteins and protein networks, edited by Ronald L.
Koder and J.L. Ross Anderson.
PMID- 26435389
TI - Unraveling the electron transfer processes of a nanowire protein from Geobacter
sulfurreducens.
AB - The extracellular electron transfer metabolism of Geobacter sulfurreducens is
sustained by several multiheme c-type cytochromes. One of these is the dodecaheme
cytochrome GSU1996 that belongs to a new sub-class of c-type cytochromes. GSU1996
is composed by four similar triheme domains (A-D). The C-terminal half of the
molecule encompasses the domains C and D, which are connected by a small linker
and the N-terminal half of the protein contains two domains (A and B) that form
one structural unit. It was proposed that this protein works as an electrically
conductive device in G. sulfurreducens, transferring electrons within the
periplasm or to outer-membrane cytochromes. In this work, a novel strategy was
applied to characterize in detail the thermodynamic and kinetic properties of the
hexaheme fragment CD of GSU1996. This characterization revealed the electron
transfer process of GSU1996 for the first time, showing that a heme at the edge
of the C-terminal of the protein is thermodynamic and kinetically competent to
receive electrons from physiological redox partners. This information contributes
towards understanding how this new sub-class of cytochromes functions as
nanowires, and also increases the current knowledge of the extracellular electron
transfer mechanisms in G. sulfurreducens.
PMID- 26435390
TI - Estimation of the driving force for dioxygen formation in photosynthesis.
AB - Photosynthetic water oxidation to molecular oxygen is carried out by photosystem
II (PSII) over a reaction cycle involving four photochemical steps that drive the
oxygen-evolving complex through five redox states Si (i = 0,..., 4). For
understanding the catalytic strategy of biological water oxidation it is
important to elucidate the energetic landscape of PSII and in particular that of
the final S4 -> S0 transition. In this short-lived chemical step the four
oxidizing equivalents accumulated in the preceding photochemical events are used
up to form molecular oxygen, two protons are released and at least one substrate
water molecule binds to the Mn4CaO5 cluster. In this study we probed the
probability to form S4 from S0 and O2 by incubating YD-less PSII in the S0 state
for 2-3 days in the presence of (18)O2 and H2(16)O. The absence of any measurable
(16,18)O2 formation by water-exchange in the S4 state suggests that the S4 state
is hardly ever populated. On the basis of a detailed analysis we determined that
the equilibrium constant K of the S4 -> S0 transition is larger than 1.0 * 10(7)
so that this step is highly exergonic. We argue that this finding is consistent
with current knowledge of the energetics of the S0 to S4 reactions, and that the
high exergonicity is required for the kinetic efficiency of PSII.
PMID- 26435391
TI - Arsenic accumulation in Brassicaceae seedlings and its effects on growth and
plant anatomy.
AB - We wished to evaluate the effects of arsenic on the morphology and anatomy of
Brassica oleracea, Raphanus sativus, Brassica juncea, Brassica oleracea var.
capitata and Brassica oleracea var. italica. Seeds were subjected to
concentrations 0uM, 250uM, 350uM and 450uM arsenic in the form of sodium arsenate
(Na2HAsO4.7H2O) during 12 days. All species accumulated more arsenic in the roots
than in the shoots, except for B. oleracea var. capitata. There was no difference
of translocation factor between species and treatments. Growth decrease was
observed in roots of B. oleracea and R. sativus, and in shoots of R. sativus and
B. oleracea var. italica. All species presented anatomical alterations in the
roots, such as: cell hypertrophy, protoplast retraction, cellular plasmolysis,
and necrotic regions. B. juncea presented collapse and hypertrophy of cells from
the leaf blade tissues. Quantitative anatomical analyses performed on the root
and leaves of B. oleracea and B. juncea revealed that arsenic interfered on the
root vascular cylinder diameter and on height of epidermal cells of the adaxial
leaf surface of both species. We concluded that arsenic was absorbed from the
culture medium and induced alterations both on root and shoot growth of the
seedlings. Retention of arsenic within the root was responsible for major damage
in this organ.
PMID- 26435392
TI - Integrated Proteomic and Genomic Analysis of Gastric Cancer Patient Tissues.
AB - V-erb-b2 erythroblastic leukemia viral oncogene homologue 2, known as ERBB2, is
an important oncogene in the development of certain cancers. It can form a
heterodimer with other epidermal growth factor receptor family members and
activate kinase-mediated downstream signaling pathways. ERBB2 gene is located on
chromosome 17 and is amplified in a subset of cancers, such as breast, gastric,
and colon cancer. Of particular interest to the Chromosome-Centric Human Proteome
Project (C-HPP) initiative is the amplification mechanism that typically results
in overexpression of a set of genes adjacent to ERBB2, which provides evidence of
a linkage between gene location and expression. In this report we studied patient
samples from ERBB2-positive together with adjacent control nontumor tissues. In
addition, non-ERBB2-expressing patient samples were selected as comparison to
study the effect of expression of this oncogene. We detected 196 proteins in
ERBB2-positive patient tumor samples that had minimal overlap (29 proteins) with
the non-ERBB2 tumor samples. Interaction and pathway analysis identified
extracellular signal regulated kinase (ERK) cascade and actin polymerization and
actinmyosin assembly contraction as pathways of importance in ERBB2+ and ERBB2-
gastric cancer samples, respectively. The raw data files are deposited at
ProteomeXchange (identifier: PXD002674) as well as GPMDB.
PMID- 26435393
TI - Comparative study of CT appearances in mucinous tubular and spindle cell
carcinoma and collecting duct carcinoma of the kidney.
AB - OBJECTIVE: To characterize the multidetector CT (MDCT) imaging characteristics of
mucinous tubular and spindle cell carcinoma (MTSCC) and collecting duct carcinoma
(CDC) of the kidney. METHODS: 21 patients with MTSCC and 18 patients with CDC
were studied retrospectively. MDCT was undertaken to investigate differences in
tumour characteristics. RESULTS: Five patients with MTSCC had calcifications as
did nine patients with CDC (p = 0.108). In three patients with MTSCC and four
patients with CDC, the tumours had a clear boundary (p = 0.682). No patient with
MTSCC had retroperitoneal lymph node metastasis as did five patients with CDC (p
= 0.015). 16 patients with MTSCC showed homogeneous enhancement, whereas 11
patients with CDC showed heterogeneous enhancement (p = 0.025). The attenuation
value of CDC tumours was greater than that of MTSCC and normal renal parenchyma
on an unenhanced CT (p = 0.027). MTSCC and CDC tumour enhancement was less than
the normal renal cortex and medulla in all phases (p < 0.001). Tumour enhancement
was greater for CDC than that for MTSCC in all phases (p = 0.011, p = 0.006 and p
= 0.052). CONCLUSION: Unenhanced and dynamic MDCT may aid in diagnosis and
differentiation of MTSCC and CDC of the kidney. ADVANCES IN KNOWLEDGE: This is
the first series evaluating the imaging findings of MTSCC and CDC of which we are
aware, and identification of such findings may improve diagnosis of these two
rare tumours.
PMID- 26435394
TI - Lewis acid-base 1,2-addition reactions: synthesis of pyrylium borates from en
ynoate precursors.
AB - Treatment of methyl (Z)-2-alken-4-ynoates with the strong Lewis acid
tris(pentafluorophenyl) borane, B(C6F5)3, yield substituted zwitterionic pyrylium
borate species via an intramolecular 6-endo-dig cyclisation reaction.
PMID- 26435398
TI - Functional analysis of an unusual type IV pilus in the Gram-positive
Streptococcus sanguinis.
AB - Type IV pili (Tfp), which have been studied extensively in a few Gram-negative
species, are the paradigm of a group of widespread and functionally versatile
nano-machines. Here, we performed the most detailed molecular characterisation of
Tfp in a Gram-positive bacterium. We demonstrate that the naturally competent
Streptococcus sanguinis produces retractable Tfp, which like their Gram-negative
counterparts can generate hundreds of piconewton of tensile force and promote
intense surface-associated motility. Tfp power 'train-like' directional motion
parallel to the long axis of chains of cells, leading to spreading zones around
bacteria grown on plates. However, S. sanguinis Tfp are not involved in DNA
uptake, which is mediated by a related but distinct nano-machine, and are unusual
because they are composed of two pilins in comparable amounts, rather than one as
normally seen. Whole genome sequencing identified a locus encoding all the genes
involved in Tfp biology in S. sanguinis. A systematic mutational analysis
revealed that Tfp biogenesis in S. sanguinis relies on a more basic machinery
(only 10 components) than in Gram-negative species and that a small subset of
four proteins dispensable for pilus biogenesis are essential for motility.
Intriguingly, one of the piliated mutants that does not exhibit spreading retains
microscopic motility but moves sideways, which suggests that the corresponding
protein controls motion directionality. Besides establishing S. sanguinis as a
useful new model for studying Tfp biology, these findings have important
implications for our understanding of these widespread filamentous nano-machines.
PMID- 26435399
TI - Corrigendum: Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes
confers human age-associated mitochondrial respiration defects.
PMID- 26435400
TI - Germanium: a new catalyst for diamond synthesis and a new optically active
impurity in diamond.
AB - Diamond attracts considerable attention as a versatile and technologically useful
material. For many demanding applications, such as recently emerged quantum
optics and sensing, it is important to develop new routes for fabrication of
diamond containing defects with specific optical, electronic and magnetic
properties. Here we report on successful synthesis of diamond from a germanium
carbon system at conditions of 7 GPa and 1,500-1,800 degrees C. Both
spontaneously nucleated diamond crystals and diamond growth layers on seeds were
produced in experiments with reaction time up to 60 h. We found that diamonds
synthesized in the Ge-C system contain a new optical centre with a ZPL system at
2.059 eV, which is assigned to germanium impurities. Photoluminescence from this
centre is dominated by zero-phonon optical transitions even at room temperature.
Our results have widened the family of non-metallic elemental catalysts for
diamond synthesis and demonstrated the creation of germanium-related optical
centres in diamond.
PMID- 26435401
TI - Delayed Carotid Dissection Following Lower Lip Revascularization in the Setting
of Hyoid Fracture--A Case Report and Review of the Literature.
AB - Traumatic injuries to the lip are common, but injuries that require
revascularization of the lower lip are infrequent and pose a major challenge to
the reconstructive surgeon. This report describes the case of a 53-year-old woman
who sustained a lower lip avulsion injury, a comminuted mandibular parasymphyseal
fracture, and a hyoid bone fracture secondary to a bicycle accident. Trauma
workup included computed tomographic angiography of the head and neck, which did
not show vascular injury. Despite successful revascularization of the lower lip,
on postoperative day 11 the patient developed a large internal carotid artery
dissection and middle cerebral artery stroke. This case highlights the importance
of careful postoperative monitoring after high-energy facial trauma, particularly
in the setting of vascular and bony injuries.
PMID- 26435402
TI - Distinguishing time-delayed causal interactions using convergent cross mapping.
AB - An important problem across many scientific fields is the identification of
causal effects from observational data alone. Recent methods (convergent cross
mapping, CCM) have made substantial progress on this problem by applying the idea
of nonlinear attractor reconstruction to time series data. Here, we expand upon
the technique of CCM by explicitly considering time lags. Applying this extended
method to representative examples (model simulations, a laboratory predator-prey
experiment, temperature and greenhouse gas reconstructions from the Vostok ice
core, and long-term ecological time series collected in the Southern California
Bight), we demonstrate the ability to identify different time-delayed
interactions, distinguish between synchrony induced by strong unidirectional
forcing and true bidirectional causality, and resolve transitive causal chains.
PMID- 26435403
TI - Highly Efficient, Color-Reproducible Full-Color Electroluminescent Devices Based
on Red/Green/Blue Quantum Dot-Mixed Multilayer.
AB - Over the past few years the performance of colloidal quantum dot-light-emitting
diode (QLED) has been progressively improved. However, most of QLED work has been
fulfilled in the form of monochromatic device, while full-color-enabling white
QLED still remains nearly unexplored. Using red, green, and blue quantum dots
(QDs), herein, we fabricate bichromatic and trichromatic QLEDs through sequential
solution-processed deposition of poly(9-vinlycarbazole) (PVK) hole transport
layer, two or three types of QDs-mixed multilayer, and ZnO nanoparticle electron
transport layer. The relative electroluminescent (EL) spectral ratios of
constituent QDs in the above multicolored devices are found to inevitably vary
with applied bias, leading to the common observation of an increasing
contribution of a higher-band gap QD EL over low-band gap one at a higher
voltage. The white EL from a trichromatic device is resolved into its primary
colors through combining with color filters, producing an exceptional color gamut
of 126% relative to National Television Systems Committee (NTSC) color space that
a state-of-the-art full-color organic LED counterpart cannot attain. Our
trichromatic white QLED also displays the record-high EL performance such as the
peak values of 23,352 cd/m(2) in luminance, 21.8 cd/A in current efficiency, and
10.9% in external quantum efficiency.
PMID- 26435404
TI - The role of putrescine in the regulation of proteins and fatty acids of thylakoid
membranes under salt stress.
AB - Polyamines can alleviate the inhibitory effects of salinity on plant growth by
regulating photosynthetic efficiency. However, little information is available to
explain the specific mechanisms underlying the contribution of polyamines to salt
tolerance of the photosynthetic apparatus. Here, we investigated the role of
putrescine (Put) on the photosynthetic apparatus of cucumber seedlings under salt
stress. We found that NaCl stress resulted in severe ion toxicity and oxidative
stress in cucumber chloroplasts. In addition, salinity caused a significant
increase in the saturated fatty acid contents of thylakoid membranes. Put altered
unsaturated fatty acid content, thereby alleviating the disintegration of
thylakoid grana lamellae and reducing the number of plastoglobuli in thylakoid
membranes. BN-PAGE revealed Put up-regulated the expression of ATP synthase,
CP47, D1, Qb, and psbA proteins and down-regulated CP24, D2, and LHCII type III
in NaCl-stressed thylakoid membranes. qRT-PCR analysis of gene expression was
used to compare transcript and protein accumulation among 10 candidate proteins.
For five of these proteins, induced transcript accumulation was consistent with
the pattern of induced protein accumulation. Our results suggest that Put
regulates protein expression at transcriptional and translational levels by
increasing endogenous polyamines levels in thylakoid membranes, which may
stabilise photosynthetic apparatus under salt stress.
PMID- 26435405
TI - Parturition failure in mice lacking Mamld1.
AB - In mice, the onset of parturition is triggered by a rapid decline in circulating
progesterone. Progesterone withdrawal occurs as a result of functional
luteolysis, which is characterized by an increase in the enzymatic activity of
20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) in the corpus luteum and is
mediated by the prostaglandin F2alpha (PGF2alpha) signaling. Here, we report that
the genetic knockout (KO) of Mamld1, which encodes a putative non-DNA-binding
regulator of testicular steroidogenesis, caused defective functional luteolysis
and subsequent parturition failure and neonatal deaths. Progesterone receptor
inhibition induced the onset of parturition in pregnant KO mice, and MAMLD1
regulated the expression of Akr1c18, the gene encoding 20alpha-HSD, in cultured
cells. Ovaries of KO mice at late gestation were morphologically unremarkable;
however, Akr1c18 expression was reduced and expression of its suppressor Stat5b
was markedly increased. Several other genes including Prlr, Cyp19a1, Oxtr, and
Lgals3 were also dysregulated in the KO ovaries, whereas PGF2alpha signaling
genes remained unaffected. These results highlight the role of MAMLD1 in labour
initiation. MAMLD1 likely participates in functional luteolysis by regulating
Stat5b and other genes, independent of the PGF2alpha signaling pathway.
PMID- 26435406
TI - Honey prevents neurobehavioural deficit and oxidative stress induced by lead
acetate exposure in male Wistar rats- a preliminary study.
AB - This research sought to investigate the possible neuroprotective effects of honey
against lead (Pb)-induced neurotoxicity. Twenty four male Wistar rats were
divided into four groups: Control group that received 1 ml/kg distilled orally
for 28 days; while groups II-IV received 0.2% lead in drinking water and 1 ml/kg
of distilled water, 1 ml/kg of honey, 1.5 ml/kg of honey respectively for 28
days. Anxiety and exploratory activities were determined in the open field test.
Memory function was determined using Morris water maze after which the animals
were sacrificed. The brains were then excised, homogenized and Lipid peroxidation
(MDA), Superoxide dismutase (SOD), Catalase, Glutathione (GSH) and Glutathione -S
Transferase (GST) activities were determined in the brains. Results showed that
lead exposure causes decrease in locomotor and exploratory activities; increase
anxiety, memory impairment, lipid peroxidation and decrease antioxidant
activities. However, co-administration of honey with lead inhibited neurotoxicity
as indicated by the improvement in memory function as evidenced by decreased
latency period and increased in time spent in target quadrant in honey-fed rats
compared to the lead-exposed animals. Furthermore, honey increased locomotion,
exploration and decreased anxiety in lead-exposed rats as indicated by the
frequency of rearing, freezing duration and the number of line crossed by
animals. Also administration of honey improves antioxidant activities as shown by
increased brain SOD, GST and GSH activities compared to the lead-treated groups
but no significant effect on MDA level. It can be concluded that honey has
neuroprotective effects against lead-induced cognitive deficit probably by
enhancing antioxidant activities.
PMID- 26435407
TI - Effects of common chronic medical conditions on psychometric tests used to
diagnose minimal hepatic encephalopathy.
AB - Many chronic medical conditions are accompanied by cognitive disturbances but
these have only to a very limited extent been psychometrically quantified. An
exception is liver cirrhosis where hepatic encephalopathy is an inherent risk and
mild forms are diagnosed by psychometric tests. The preferred diagnostic test
battery in cirrhosis is often the Continuous Reaction Time (CRT) and the
Portosystemic Encephalopathy (PSE) tests but the effect on these of other medical
conditions is not known. We aimed to examine the effects of common chronic (non
cirrhosis) medical conditions on the CRT and PSE tests. We studied 15 patients
with heart failure (HF), 15 with end stage renal failure (ESRF), 15 with
dysregulated type II diabetes (DMII), 15 with chronic obstructive pulmonary
disease (COPD), and 15 healthy persons. We applied the CRT test, which is a 10
min computerized test measuring sustained attention and reaction time stability
and the PSE test, which is a paper-pencil test battery consisting of 5 subtests.
We found that a high fraction of the patients with HF (8/15, 0.002) or COPD
(7/15, p = 0.006) had pathological CRT test results; and COPD patients also
frequently had an abnormal PSE test result (6/15, p < 0.0001). Both tests were
unaffected by ESRF and DMII. Half of the patients with HF or COPD had
psychometrically measurable cognitive deficits, whereas those with ESRF or DMII
had not. This adds to the understanding of the clinical consequences of chronic
heart- and lung disease, and implies that the psychometric tests should be
interpreted with great caution in cirrhosis patients with heart- or lung
comorbidity.
PMID- 26435408
TI - PAX4 Gene Transfer Induces alpha-to-beta Cell Phenotypic Conversion and Confers
Therapeutic Benefits for Diabetes Treatment.
AB - The transcription factor Pax4 plays a critical role in the determination of alpha
versus beta-cell lineage during endocrine pancreas development. In this study,
we explored whether Pax4 gene transfer into alpha-cells could convert them into
functional beta-cells and thus provide therapeutic benefits for insulin-deficient
diabetes. We found that Pax4 delivered by adenoviral vector, Ad5.Pax4, induced
insulin expression and reduced glucagon expression in alphaTC1.9 cells. More
importantly, these cells exhibited glucose-stimulated insulin secretion, a key
feature of functional beta-cells. When injected into streptozotocin-induced
diabetic mice, Pax4-treated alphaTC1.9 cells significantly reduced blood glucose,
and the mice showed better glucose tolerance, supporting that Pax4 gene transfer
into alphaTC1.9 cells resulted in the formation of functional beta-cells.
Furthermore, treatment of primary human islets with Ad5.Pax4 resulted in
significantly improved beta-cell function. Detection of
glucagon(+)/Pax4(+)/Insulin(+) cells argued for Pax4-induced alpha-to-beta cell
transitioning. This was further supported by quantification of glucagon and
insulin bi-hormonal cells, which was significantly higher in Pax4-treated islets
than in controls. Finally, direct administration of Ad5.Pax4 into the pancreas of
insulin-deficient mice ameliorated hyperglycemia. Taken together, our data
demonstrate that manipulating Pax4 gene expression represents a viable
therapeutic strategy for the treatment of insulin deficient diabetes.
PMID- 26435410
TI - Effect of self-assembling peptide P11 -4 on enamel erosion: AFM and SEM studies.
AB - The aim of the present in vitro study was to evaluate the protective effect of
self-assembling peptide P11 -4 (CurodontTM Protect/Credentis) on enamel erosion
produced by a soft-drink, by using Atomic Force Microscopy (AFM) and Scanning
Electron Microscopy (SEM). Thirty human incisors were equally and randomly
assigned to 6 groups. Group 1: intact enamel, group 2: soft drink, group 3:
Curodont(TM) Protect applied, group 4: Curodont(TM) Protect applied + soft drink,
group 5: soft drink + Curodont(TM) Protect applied, group 6: soft drink +
Curodont(TM) Protect applied + soft drink. Specimens were observed through atomic
force microscopy (AFM). The root mean-square roughness (Rrms) was obtained from
the AFM images and the differences in the averaged values among the groups were
analyzed by Shapiro-Wilk test in order to assess the normality of the
distribution. Parametric ANOVA and post hoc Tuckey test were performed to assess
the differences between the different groups. After demineralization process,
enamel demonstrated a high degree of surface porosity. This morphological aspect
was reflected in the increase of Rrms values. No significant differences (p >
0.05) were reported between intact enamel and enamel only treated with P11 -4 and
between eroded enamel and enamel treated with P11 -4 and then demineralized.
However significant differences (p < 0.05) were recorded when comparing softened
enamel with softened enamel further remineralized with biomimetic self-assembling
peptides and enamel treated with the protective paste between two acid attacks.
The use of P11 -4 remineralizing may offer a degree of protection from enamel
erosion. SCANNING 38:344-351, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26435409
TI - Modeling Human Bone Marrow Failure Syndromes Using Pluripotent Stem Cells and
Genome Engineering.
AB - The combination of epigenetic reprogramming with advanced genome editing
technologies opened a new avenue to study disease mechanisms, particularly of
disorders with depleted target tissue. Bone marrow failure syndromes (BMFS)
typically present with a marked reduction of peripheral blood cells due to a
destroyed or dysfunctional bone marrow compartment. Somatic and germline
mutations have been etiologically linked to many cases of BMFS. However, without
the ability to study primary patient material, the exact pathogenesis for many
entities remained fragmentary. Capturing the pathological genotype in induced
pluripotent stem cells (iPSCs) allows studying potential developmental defects
leading to a particular phenotype. The lack of hematopoietic stem and progenitor
cells in these patients can also be overcome by differentiating patient-derived
iPSCs into hematopoietic lineages. With fast growing genome editing techniques,
such as CRISPR/Cas9, correction of disease-causing mutations in iPSCs or
introduction of mutations in cells from healthy individuals enable comparative
studies that may identify other genetic or epigenetic events contributing to a
specific disease phenotype. In this review, we present recent progresses in
disease modeling of inherited and acquired BMFS using reprogramming and genome
editing techniques. We also discuss the challenges and potential shortcomings of
iPSC-based models for hematological diseases.
PMID- 26435411
TI - Expanding horizons of cellular plasticity in regenerative medicine.
AB - This Guest Editorial introduces the Regenerative Medicine Theme Issue, which
provides critical insight into the unfolding frontier of regenerative medicine.
PMID- 26435412
TI - Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and
modulated by telmisartan.
AB - Traumatic brain injury affects the whole body in addition to the direct impact on
the brain. The systemic response to trauma is associated with the hepatic acute
phase response. To further characterize this response, we performed controlled
cortical impact injury on male mice and determined the expression of serum
amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute
phase response in liver and plasma. After cortical impact injury, induction of
SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post
injury, followed by gradual diminution over time. In the liver, cortical impact
injury increased neutrophil and macrophage infiltration, apoptosis, and
expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in
angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed.
Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury
significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not
affect CXCL1 expression or the number of apoptotic cells or infiltrating
leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is
induced in the liver after traumatic brain injury and that telmisartan prevents
this response. Elucidating the molecular pathogenesis of the liver after brain
injury will assist in understanding the efficacy of therapeutic approaches to
brain injury.
PMID- 26435414
TI - Sphingosine-1-phosphate receptor antagonism enhances proliferation and migration
of engrafted neural progenitor cells in a model of viral-induced demyelination.
AB - The oral drug FTY720 affects sphingosine-1-phosphate (S1P) signaling on targeted
cells that bear the S1P receptors S1P1, S1P3, S1P4, and S1P5. We examined the
effect of FTY720 treatment on the biology of mouse neural progenitor cells (NPCs)
after transplantation in a viral model of demyelination. Intracerebral infection
with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in an
acute encephalomyelitis, followed by demyelination similar in pathology to the
human demyelinating disease, multiple sclerosis. We have previously reported that
intraspinal transplantation of mouse NPCs into JHMV-infected animals resulted in
selective colonization of demyelinated lesions, preferential differentiation into
oligodendroglia accompanied by axonal preservation, and increased remyelination.
Cultured NPCs expressed transcripts for S1P receptors S1P1, S1P2, S1P3, S1P4, and
S1P5. FTY720 treatment of cultured NPCs resulted in increased mitogen-activated
protein kinase phosphorylation and migration after exposure to the chemokine
CXCL12. Administration of FTY720 to JHMV-infected mice resulted in enhanced
migration and increased proliferation of transplanted NPCs after spinal cord
engraftment. FTY720 treatment did not improve clinical disease, diminish
neuroinflammation or the severity of demyelination, nor increase remyelination.
These findings argue that FTY720 treatment selectively increases NPC
proliferation and migration but does not either improve clinical outcome or
enhance remyelination after transplantation into animals in which immune-mediated
demyelination is initiated by the viral infection of the central nervous system.
PMID- 26435413
TI - Deletion of Galgt2 (B4Galnt2) reduces muscle growth in response to acute injury
and increases muscle inflammation and pathology in dystrophin-deficient mice.
AB - Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle
stimulates the glycosylation of alpha dystroglycan (alphaDG) and the up
regulation of laminin alpha2 and dystrophin surrogates known to inhibit muscle
pathology in mouse models of congenital muscular dystrophy 1A and Duchenne
muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally
increased in the mdx mouse model of Duchenne muscular dystrophy compared with the
wild-type mice. To assess whether this increased endogenous Galgt2 expression
could affect disease, we quantified muscular dystrophy measures in mdx mice
deleted for Galgt2 (Galgt2(-/-)mdx). Galgt2(-/-) mdx mice had increased heart and
skeletal muscle pathology and inflammation, and also worsened cardiac function,
relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also
slowed skeletal muscle growth in response to acute muscle injury. In each
instance where Galgt2 expression was elevated (developing muscle, regenerating
muscle, and dystrophic muscle), Galgt2-dependent glycosylation of alphaDG was
also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle
pathology in dystroglycan-deficient muscles, in contrast to previous studies in
dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene
expression and glycosylation of alphaDG are dynamically regulated in muscle and
that endogenous Galgt2 gene expression can ameliorate the extent of muscle
pathology, inflammation, and dysfunction in mdx mice.
PMID- 26435416
TI - In Vitro Bioaccessibility and Bioavailability of Iron from Potatoes with Varying
Vitamin C, Carotenoid, and Phenolic Concentrations.
AB - The bioaccessibility and bioavailability of iron from 12 Andean potato clones
were estimated using an in vitro gastrointestinal digestion procedure and the
Caco-2 cell line as a model of human intestine, with ferritin formation as a
marker of iron absorption. We first showed that 63.7% (for the genotype
CIP_311422.016) to 79.0% (for the genotype CIP_311575.003) of the iron is
released from the potato tuber matrix during in vitro gastrointestinal digestion
and is therefore available at the intestinal level. On average, 32 and 24.5% of
the hydrophilic bioactive components, vitamin C and chlorogenic acid,
respectively, were also bioaccessible from boiled tubers. Intestinal absorption
of intrinsic iron from potato tubers could not be detected using our in vitro
Caco-2 cell model. When an extrinsic source of iron (20 MUM FeCl3 and 1 mM
ascorbic acid) was added to the digestion mixture, iron absorption varied from
1.8 to 8% for the genotypes CIP_311422.016 and CIP_311624.021, respectively, as
compared to the reference control. Principal component analysis revealed negative
relationships between bioavailable iron values and phenolic concentrations,
whereas vitamin C concentrations were positively associated with the ferritin
values. Further controlled intervention trials would be needed to conclusively
assess the bioavailability of intrinsic iron from potato tubers.
PMID- 26435415
TI - Human polycystin-2 transgene dose-dependently rescues ADPKD phenotypes in Pkd2
mutant mice.
AB - Although much is known about the molecular genetic mechanisms of autosomal
dominant polycystic kidney disease (ADPKD), few effective treatment is currently
available. Here, we explore the in vivo effects of causal gene replacement in
orthologous gene models of ADPKD in mice. Wild-type mice with human PKD2
transgene (PKD2(tg)) overexpressed polycystin (PC)-2 in several tissues,
including the kidney and liver, and showed no significant cyst formation in
either organ. We cross-mated PKD2(tg) with a Pkd2-null mouse model, which is
embryonically lethal and forms renal and pancreatic cysts. Pkd2(-/-) mice with
human PKD2 transgene (Pkd2(-/-);PKD2(tg)) were born in expected Mendelian ratios,
indicating that the embryonic lethality of the Pkd2(-/-) mice was rescued. Pkd2(
/-);PKD2(tg) mice survived up to 12 months and exhibited moderate to severe
cystic phenotypes of the kidney, liver, and pancreas. Moreover, Pkd2(-/-) mice
with homozygous PKD2(tg)-transgene alleles (Pkd2(-/-);PKD2(tg/tg)) showed
significant further amelioration of the cystic severity compared to that in Pkd2(
/-) mice with a hemizygous PKD2(tg) allele (Pkd2(-/-);PKD2(tg)), suggesting that
the ADPKD phenotype was improved by increased transgene dosage. On further
analysis, cystic improvement mainly resulted from reduced proliferation, rather
apoptosis, of cyst-prone epithelial cells in the mouse model. The finding that
the functional restoration of human PC2 significantly rescued ADPKD phenotypes in
a dose-dependent manner suggests that increasing PC2 activity may be beneficial
in some forms of ADPKD.
PMID- 26435417
TI - HIV Infection Is Associated with Impaired Striatal Function during Inhibition
with Normal Cortical Functioning on Functional MRI.
AB - The aim of the present study was to investigate the effect of HIV infection on
cortical and subcortical regions of the frontal-striatal system involved in the
inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that
human immunodeficiency virus (HIV) infection is associated with frontostriatal
dysfunction. While frontostriatal systems play a key role in behavioral
inhibition, there are to our knowledge no fMRI studies investigating the
potential impact of HIV on systems involved during the inhibition of voluntary
movement. A total of 17 combined antiretroviral therapy (cART) naive HIV+
participants as well as 18 age, gender, ethnic, education matched healthy
controls performed a modified version of the stop-signal paradigm. This paradigm
assessed behavior as well as functional brain activity associated with motor
execution, reactive inhibition (outright stopping) and proactive inhibition
(anticipatory response slowing before stopping). HIV+ participants showed
significantly slower responses during motor execution compared to healthy
controls, whereas they had normal proactive response slowing. Putamen
hypoactivation was evident in the HIV+ participants based on successful stopping,
indicating subcortical dysfunction during reactive inhibition. HIV+ participants
showed normal cortical functioning during proactive inhibition. Our data provide
evidence that HIV infection is associated with subcortical dysfunction during
reactive inhibition, accompanied by relatively normal higher cortical functioning
during proactive inhibition. This suggests that HIV infection may primarily
involve basic striatal-mediated control processes in cART naive participants.
PMID- 26435419
TI - Quantitative proteomic analysis of Araucaria angustifolia (Bertol.) Kuntze cell
lines with contrasting embryogenic potential.
AB - GeLC-MS/MS based label free proteomic profiling was used in the large scale
identification and quantification of proteins from Brazilian pine (Araucaria
angustifolia) embryogenic cell (EC) lines that showed different propensities to
form somatic embryos. Using a predicted protein sequence database that was
derived from A. angustifolia RNA-Seq data, 2398 non-redundant proteins were
identified. The log2 of the spectral count values of 858 proteins of these
proteins showed a normal distribution, and were used for statistical analysis.
Statistical tests indicated that 106 proteins were significantly differentially
abundant between the two EC lines, and that 35 were more abundant in the
responsive genotype (EC line SE1) and 71 were more abundant in the blocked
genotype (EC line SE6). An increase in the abundance of proteins related to cell
defense, anti-oxidative stress responses, and storage reserve deposition was
observed in SE1. Moreover, in SE6 we observed an increased abundance of two
proteins associated with seed development during the embryogenic cell
proliferation stage, which we suggest is associated with genotypes showing a low
responsiveness to embryo formation. Differences in protein abundance between the
EC lines are discussed in terms of carbohydrate metabolism, cell division,
defense response, gene expression, and response to reactive oxygen species.
PMID- 26435418
TI - SILAC-based proteomic analysis reveals that salidroside antagonizes cobalt
chloride-induced hypoxic effects by restoring the tricarboxylic acid cycle in
cardiomyocytes.
AB - Hypoxic status alters the energy metabolism and induces cell injury in
cardiomyocytes, and it further triggers the occurrence and development of
cardiovascular diseases. Our previous studies have shown that salidroside (SAL)
exhibits anti-hypoxic activity. However, the mechanisms remain obscure. In the
present study, we successfully screened 92 different expression proteins in CoCl2
induced hypoxic conditions, 106 different expression proteins in the SAL-mediated
anti-hypoxic group were compared with the hypoxic group using quantitative
proteomics strategy, respectively. We confirmed that SAL showed a positive
protective function involving the acetyl-CoA metabolic, tricarboxylic acid (TCA)
cycle using bioinformatics analysis. We also demonstrated that SAL plays a
critical role in restoring the TCA cycle and in protecting cardiomyocytes from
oxidative injury via up-regulation expressions of PDHE1-B, ACO2, SUCLG1, SUCLG2
and down-regulation of MDH2. SAL also inhibited H9c2 cell apoptosis by inhibiting
the activation of pro-apoptotic molecules caspase 3 and caspase 9 as well as
activation of the anti-apoptotic molecular Bcl-2. Additionally, SAL also improved
mitochondrial membrane potential (DeltaPsim), reduced reactive oxygen species
(ROS) and intercellular Ca(2+) concentration ([Ca(2+)]i) accumulation and
inhibited the excessive consumption of ATP in H9c2 cells.
PMID- 26435420
TI - Putrescine induces somatic embryo development and proteomic changes in
embryogenic callus of sugarcane.
AB - Somatic embryogenesis, an important biotechnological technique, has great
potential for application in sugarcane breeding and micropropagation. Polyamines
have been associated with the regulation of several physiological processes,
including the acquisition of embryogenic competence and somatic embryogenesis. In
this study, we used a proteomic approach to evaluate the effects of exogenous
polyamine on sugarcane somatic embryo development to better understand this
process. Embryogenic cultures were treated with different concentrations of
putrescine, spermidine, and spermine. Proteomic analyses combined the shotgun
method and the nanoESI-HDMS(E) technology. Among polyamines, 500 MUM putrescine
gave rise to the highest number of somatic embryos; however, no differences in
the amount of fresh matter were observed between polyamines and control.
Differences in protein abundance profiles resulting from the effect of 500 MUM
putrescine on sugarcane somatic embryo maturation were observed. Proteomic
analyses of putrescine and control treatment showed differences in the abundances
of proteins related to somatic embryogenesis, such as arabinogalactan proteins,
peroxidases, heat shock proteins, glutathione s-transferases, late embryogenesis
abundant proteins, and 14-3-3 proteins. These results show that putrescine and
the identified proteins play important roles in protecting the cells against an
in vitro stress environment, contributing to the formation of somatic embryos
during the maturation treatment. BIOLOGICAL SIGNIFICANCE: Despite all studies
with somatic embryogenesis, the molecular mechanisms controlling the process have
not been completely understood. In this study, we highlighted the effects of the
polyamine putrescine on somatic embryogenesis of sugarcane and the differentially
abundant proteins related to somatic embryo development. We identified six groups
of important stress related proteins that are involved in the adaptation of cells
to the stress environment of in vitro culture and may also be part of the
mechanisms associated to the somatic embryogenesis process. Therefore, our
research is trying to understand the complexity of how one single somatic cell
becomes a whole plant.
PMID- 26435421
TI - Membrane composition influences the activity of in vitro refolded human vitamin K
epoxide reductase.
AB - Human vitamin K epoxide reductase (hVKOR) is an integral membrane protein
responsible for the maintenance of reduced vitamin K pools, a prerequisite for
the action of gamma-glutamyl carboxylase and hence for hemostasis. Here we
describe the recombinant expression of hVKOR as an insoluble fusion protein in
Escherichia coli, followed by purification and chemical cleavage under denaturing
conditions. In vitro renaturation and reconstitution of purified solubilized
hVKOR in phospholipids could be established to yield active protein. Crucially,
the renatured enzyme is inhibited by the powerful coumarin anticoagulant
warfarin, and we demonstrate that enzyme activity depends on lipid composition.
The completely synthetic system for protein production allows a rational
investigation of the multiple variables in membrane protein folding and paves the
way for the provision of pure, active membrane protein for structural studies.
PMID- 26435422
TI - Immunolocalization and distribution of proteoglycans in carious dentine.
AB - BACKGROUND: Collagen type I, proteoglycans (PG) and non-collagenous proteins
represent important building blocks of the dentine matrix. While different PGs
have been identified in dentine, changes in the distribution of these
macromolecules with the progression of caries have been poorly characterized. The
aim of this study was to compare the immunolocalization of three small collagen
binding PGs (biglycan, fibromodulin and lumican) as well as collagen (types I and
VI) in healthy versus carious dentine. METHODS: Longitudinal demineralized
sections of extracted teeth were stained with antibodies recognizing specific PG
core proteins and collagens, as well as glycosaminoglycans (GAGs) with toluidine
blue. RESULTS: In healthy dentine, PGs appeared to be more abundant near the
tubule walls and directly under the cusps. Conversely, in carious dentine,
specific locations appeared to be more prone to PG degradation than others. These
degradation patterns were well correlated with the progression of caries into the
tissue, and also appeared to trigger interesting morphological changes in the
tissue structure, such as the deformation of dentine tubules near highly infected
areas and the lower concentration of PG in tertiary dentine. CONCLUSIONS: This
study presents new insights into the involvement of PGs in the progression of
caries.
PMID- 26435423
TI - Pt/Fe3O4 Core/Shell Triangular Nanoprisms by Heteroepitaxy: Facet Selectivity at
the Pt-Fe3O4 Interface and the Fe3O4 Outer Surface.
AB - Pt/Fe3O4 core/shell triangular nanoprisms were synthesized using seed-mediated
heteroepitaxy. Their well-defined shape, facets, and ordered-assembly allowed
detailed analysis of mechanism of the heteroepitaxy. At the Pt-Fe3O4 interface,
existence of both lattice and chemical mismatch resulted in facet-selective
epitaxy along ?111? directions of two lattices. X-ray absorption fine structure
measurements demonstrated that the Pt seed nanocrystals were composed of an iron
rich Pt-Fe metallic thin layer sandwiched between the Pt core and a Fe-O outer
surface. The Fe-O outer-surface of the seed nanocrystals presumably offered
epitaxial sites for the following deposition of the Fe3O4 shell. Each tip and
side of a triangular nanoprism respectively possessed a groove and a ridge, and a
(111) plane parallel to the basal planes linked all grooves and ridges. This
interesting (111) plane approximately bisected the triangle nanoprisms and
located near the Pt-seed. The outer surface of the hybrid nanocrystals was also
found to be facet-selective, that is, solely {111} facets of Fe3O4 lattice. These
polar {111} facets allowed the surface to be only occupied with high-density iron
ions, and thus offered best surface coordination for the electron donating
ligands in the solution.
PMID- 26435424
TI - Discussion.
PMID- 26435425
TI - FGF23, metabolic risk factors, and blood pressure in patients with primary
hyperparathyroidism undergoing parathyroid adenomectomy.
AB - BACKGROUND: Fibroblast growth factor-23 (FGF23), a regulator of secretion of
parathyroid hormone (PTH), is implicated in the development of cardiovascular
disease. The role of FGF23 in primary hyperparathyroidism (pHPT) is unclear.
METHODS: A total of 150 consecutive patients with pHPT were examined with
ambulatory blood pressure monitoring ((24h)ABP) before parathyroid adenomectomy
(PTX). Blood samples were collected 6 +/- 2 weeks before and 6 +/- 2 weeks after
PTX. RESULTS: Plasma FGF23 levels decreased after PTX from a median of 45.2 pg/mL
(interquartile range 37.6-54.8) to 36.8 pg/mL (26.7-48.7); P < .001. This
postoperative decrease correlated with the decrease in ionized calcium (r = 0.24;
P < .01). Greater FGF23 concentrations at baseline were associated with a greater
weight of the adenoma and PTH levels, as well as with body mass index,
triglycerides, and insulin levels and greater postoperative decreases in FGF23,
ionized calcium, insulin growth-like factor 1, and insulin. FGF23 and PTH both
correlated with greater blood pressures on (24h)ABP, especially at nighttime (r =
0.31 and r = 0.28; P <= .01), whereas after multivariate adjustment, only PTH
remained independently associated with (24)ABP. CONCLUSION: Circulating FGF23 is
increased in pHPT and is associated independently with the metabolic risk
profile. The long-term benefit of decreasing FGF23 in pHPT after PTX remains to
be established.
PMID- 26435426
TI - Same thyroid cancer, different national practice guidelines: When discordant
American Thyroid Association and National Comprehensive Cancer Network surgery
recommendations are associated with compromised patient outcome.
AB - BACKGROUND: The American Thyroid Association (ATA) and National Comprehensive
Cancer Network (NCCN) guidelines have discordant recommendations for managing
patients with differentiated thyroid cancer (DTC). We hypothesized that physician
adherence to either of the 2009 extent of surgery guidelines of the ATA or NCCN
was associated with improved survival, and that practice is most standardized
nationally when guidelines are concordant. METHODS: Adult patients undergoing
surgery for DTC were included from the National Cancer Database. Multivariable
modeling was used to identify factors associated with nonadherence to the 2009
ATA or NCCN guidelines (2010-2011) and hypothetically examine the association of
retrospective adherence to guidelines with survival (1998-2006). RESULTS: A total
of 39,687 patients with DTC were included; 2,249 were not treated in accordance
with ATA or NCCN guidelines. Factors independently associated with nonadherence
were discordance between ATA and NCCN recommendations, black race, and treatment
at nonacademic centers (P < .01). After adjustment, care not in accordance with
either set of guidelines was associated with compromised survival (hazard ratio
1.16, P = .02). CONCLUSION: A minority of patients received surgery for DTC not
aligned with guidelines; nonadherent care was associated with compromised
survival. Discordance in recommendations between guidelines is associated with
reduction in adherent care, suggesting that standardizing guidelines could
decrease confusion, increase adherence, and thereby may improve outcomes.
PMID- 26435427
TI - Cost disparity between health care systems--it's not the surgeons: A cost
analysis of thyroid cancer care between the United States and France.
AB - BACKGROUND: The cost disparity between the United States and other advanced
health care systems, including France, is expanding. In this report we identified
the management of papillary thyroid cancer (PTC) that contribute to reimbursement
disparity. METHODS: A tri-institutional, retrospective review included 200
patients with PTC (100 from the United States, 100 from France) treated by total
thyroidectomy with/without central neck dissection. A cost model was generated
incorporating perioperative management variables (within 1 year) and their
reimbursement rates according to the 2014 US Medicare and French government fee
schedules. RESULTS: In the United States, total thyroidectomy with central neck
dissection was more frequent (92% vs 35%, P < .001), median duration of stay was
less (1 vs 3 days, P < .001), and use of radioactive iodine was less (66% vs 93%,
P < .001), although Thyrogen stimulation was more prevalent (100% vs 43%, P <
.001). Overall, the median cost per patient was greater in the United States
($14,069 vs $4,590, P < .001). Reimbursements to the hospital facility accounted
for 70% of the disparity, despite lesser durations of stay. Nuclear medicine
accounted for 19%, mostly from Thyrogen reimbursement despite less use of
radioactive iodine. Surgeon fees accounted for 6%, followed by office visits,
laboratory/imaging, anesthesia/pathology fees, and medications. CONCLUSION: The
costs of management of PTC are substantially greater in the US compared with
France. Efforts to decrease this disparity should focus on reimbursements for
hospital facility and use of nuclear medicine imaging.
PMID- 26435428
TI - Effect of malignancy rates on cost-effectiveness of routine gene expression
classifier testing for indeterminate thyroid nodules.
AB - BACKGROUND: The value of gene expression classifier (GEC) testing for
cytologically indeterminate thyroid nodules lies in its negative predictive
value, which is influenced by the prevalence of malignancy. We incorporated
actual GEC test performance data from a tertiary referral center into a cost
effectiveness analysis of GEC testing. METHODS: We evaluated consecutive patients
who underwent GEC testing for Bethesda category III and IV nodules from 2012 to
2014. Routine GEC testing was compared with conventional management by the use of
a decision tree model. Additional model variables were determined via literature
review. A cost-effectiveness threshold of $100,000 per quality-adjusted life-year
(QALY) was used. RESULTS: The prevalence of malignancy was 24.3% (52/214).
Sensitivity and specificity of GEC testing were 96% and 60%. Conventional
management cost $11,119 and yielded 22.15 QALYs. Routine GEC testing was more
effective and more costly, with an incremental cost-effectiveness ratio of
$119,700/QALY, making it not cost-effective. At malignancy rates of 15, 25, or
35%, routine GEC testing became cost-effective when the cost of GEC testing fell
below $3,167, $2,595, or $2,023. CONCLUSION: The cost-effectiveness of routine
GEC testing varies inversely with the underlying prevalence of malignancy in the
tested population. The value of routine GEC testing should be assessed within the
context of institution-specific malignancy rates.
PMID- 26435429
TI - Acute deterioration after emergency paraesophageal hernia repair.
PMID- 26435430
TI - Discussion.
PMID- 26435431
TI - Diagnostic utility of data from adrenal venous sampling for primary aldosteronism
despite failed cannulation of the right adrenal vein.
AB - BACKGROUND: Adrenal venous sampling is an important lateralization study for
primary aldosteronism, but inability to cannulate the right adrenal vein is not
uncommon and interpreted as a failed study. We challenged this notion by
examining whether data from incomplete left-sided adrenal venous sampling could
accurately predict lateralization. METHODS: Sixty-two adrenal venous sampling
studies from 2007 to 2014 at 2 tertiary-care institutions were reviewed. For this
analysis, data from the right adrenal vein were excluded. The study variable was
the aldosterone:cortisol ratio of the left adrenal vein compared with the
inferior vena cava (LAV/IVC). Scatterplot analysis identified high and low
LAV/IVC cutoffs that predicted accurately unilateral disease in 1 institutional
cohort and validated in the second cohort. RESULTS: Thirty-six studies of adrenal
venous sampling were evaluated at the first institution and divided into 3
diagnostic categories: unilateral-left (n = 14), unilateral-right (n = 12), and
bilateral (n = 10). Cutoff values of the ratios of LAV/IVC of >= 5.5 and <= 0.5
accurately predicted left- and right-sided disease, respectively, and were
validated in 26 studies from the second institution (100% PPV). The "5.5-0.5
criteria" salvaged accuracy for predicting lateralization in 50% of cases.
CONCLUSION: Even in the setting of failed cannulation of the right adrenal vein,
the actual data from the remaining adrenal venous sampling can predict
lateralization accurately in many patients. A "failed" adrenal venous sampling
study may be of greater predictive utility than believed traditionally.
PMID- 26435432
TI - Discussion.
PMID- 26435433
TI - Selective strategy for intensive monitoring after pheochromocytoma resection.
AB - BACKGROUND: Guidelines recommend 24-48 hours of intensive monitoring after
resection of pheochromocytoma. However, many patients do not require it. The
objective of this study is to identify preoperative risk factors associated with
postoperative hemodynamic instability (HDI) so as to select patients who may not
require intensive postoperative monitoring. METHODS: Medical records of patients
undergoing pheochromocytoma resection over a 12-year period were reviewed.
Postoperative HDI was defined as systolic blood pressure of >200 or <90, heart
rate >110 or <50 or needing active resuscitation. RESULTS: We included 41
patients; 49% had postoperative HDI but only 34% had HDI > 6 hours. Risk factors
for HDI were preoperative mean arterial pressure (MAP) > 100 mm Hg (14% vs 45%),
norepinephrine/normetanephrine levels >3x normal (44 vs 82%), and resection of
another solid organ (0 vs 20%). Avoidance of planned postoperative monitoring for
low-risk patients would have reduced estimated costs by 34%. CONCLUSION: Fewer
than one-half of patients undergoing resection for pheochromocytoma benefit from
intensive monitoring. High preoperative MAP, high norepinephrine/normetanephrine
levels, and concomitant resection of another organ are risk factors for
postoperative HDI. After a 6-hour interval of postoperative stability, selective
rather than routine use of intensive monitoring may be an efficient strategy for
monitoring lower risk patients.
PMID- 26435434
TI - A pilot study investigating the effect of parathyroidectomy on arterial stiffness
and coronary artery calcification in patients with primary hyperparathyroidism.
AB - BACKGROUND: Arterial stiffness (AS) and coronary artery calcification (CAC) are
predictors of cardiovascular risk and can be measured noninvasively. The aim of
this study was to analyze the effects of parathyroidectomy on AS and CAC in
patients with primary hyperparathyroidism (PHP). METHODS: This prospective,
institutional review board-approved study included 21 patients with PHP, who
underwent parathyroidectomy. Before and 6 months after parathyroidectomy, AS was
assessed by measuring central systolic pressure (CSP), central pulse pressure,
augmentation pressure (AP), and augmentation index (AIx); the CAC score
(Agatston) was calculated on noncontrast computed tomography. AS parameters were
compared with unaffected controls from donor nephrectomy database. RESULTS:
Preoperative CSP and AIx parameters in PHP patients were higher than those in
donor nephrectomy patients (P = .004 and P = .039, respectively). Preoperative
total CAC score was zero in 15 patients (65%) and ranged from the 72nd to the
99th percentile in 6 patients (26%). Although there were no changes in CAC or AS
after parathyroidectomy on average, there was variability in individual patient
responses on AS. CONCLUSION: This pilot study demonstrates that CAC is not
altered in PHP patients at short-term follow-up after parathyroidectomy. The
heterogeneous changes in AS after parathyroidectomy warrant further investigation
in a larger study with longer follow-up.
PMID- 26435435
TI - Discussion.
PMID- 26435436
TI - Risk factors for central lymph node metastasis in papillary thyroid carcinoma: A
National Cancer Data Base (NCDB) study.
AB - BACKGROUND: There is no consensus regarding prophylactic central lymph node
dissection (pCLND) in patients with papillary thyroid carcinoma (PTC).
Identification of risk factors for central lymph node metastasis (CLNM) in
patients with PTC could assist surgeons in determining whether to perform
selective pCLND. METHODS: The National Cancer database was queried from 1998 to
2011 for patients with clinical staging T1-4cN0M0 PTC. All patients underwent
near, sub-, or total thyroidectomy with or without pCLND. Univariate and
multivariable logistic regressions were performed on the following clinical
variables: age, sex, race and tumor size as risk factors for pathologic CLNM
(pN1a). RESULTS: In 39,562 patients with T1-4cN0M0 PTC, 61% underwent pCLND.
Patients with age >45 years, African American race, tumor size <= 1 cm, unifocal
tumors, follicular variant PTC, no insurance, and treatment at community cancer
facilities were less likely to have pCLND (P < .001). In the pCLND group, 15.6%
of patients had CLNM. On adjusted multivariable logistic regression, age <= 45
years, Asian race, male sex, and larger tumors were statistically significantly
associated with CLNM. CONCLUSION: Age <= 45 years, Asian race, male sex, and
larger tumors are associated with the presence of CLNM, which allows for
selective pCLND in PTC.
PMID- 26435437
TI - Discussion.
PMID- 26435438
TI - Outcome of inferior vena cava and noncaval venous leiomyosarcomas.
AB - BACKGROUND: Leiomyosarcoma (LMS) is a rare tumor arising from the smooth muscle
cells of arteries and veins. LMS may affect both the inferior vena cava (IVC) and
non-IVC veins. Because of its rarity, the experience with the outcome of the
disease originating from the IVC compared with that with non-IVC offspring is
overall limited. In this study, we compared the clinical features and outcomes
after operative resection of IVC and non-IVC LMS to detect possible significant
differences that could affect treatment and prognosis. METHODS: Twenty-seven
patients undergoing operative resection of a venous LMS at a single tertiary care
center and one secondary care hospital were reviewed retrospectively and divided
into 2 groups: IVC-LMS (Group A, n = 18) and non-IVC LMS (Group B, n = 9). As
primary end points, postoperative mortality and morbidity, disease-specific
survival and, if applicable, patency of venous reconstruction were considered.
Bivariate differences were compared with the chi(2) test. Disease-specific
survival was expressed by a life-table analysis and compared using the log-rank
test. RESULTS: No postoperative mortality was observed in either group.
Postoperative morbidity was 28% in group A and 11% in group B (P = .33). The mean
duration of follow-up was 60 months (range, 13-140). Disease-specific survival
was 60% in group A and 75% in group B at 3 years (P = .48), and it was 54% in
group A and 62% in group B at 5 years (P = .63). Seven grafts were occluded in
group A (39%) and 1of 3 were occluded in group B (33%) (P = .85). CONCLUSION: IVC
and non-IVC LMS exhibit similar outcomes in terms of postoperative course and
survival. Operative resection associated with vascular reconstruction, if
applicable, eventually followed by radiation and chemotherapy may be curative and
is associated with good functional results.
PMID- 26435439
TI - Discussion.
PMID- 26435441
TI - Discussion.
PMID- 26435440
TI - Recurrence of papillary thyroid carcinoma with lateral cervical node metastases:
Predictive factors and operative management.
AB - BACKGROUND: Lateral neck lymph node (LN) metastases (N1b) have been identified as
independent risk factors of recurrence in patients with papillary thyroid
carcinoma (PTC). OBJECTIVE: This study aimed to determine the predictive factors
of recurrence in N1b PTC patients and to clarify the postoperative event
patterns. METHODS: All patients who underwent operation for N1b PTC between 1978
and 2012 were reviewed. The median follow-up period was 6.5 years. RESULTS: In
total, 344 N1b patients were included. Twenty-four patients (7%) were lost to
long-term follow-up. Among the remaining 320 patients, the mean (+/- SD) follow
up time was 8.9 +/- 8.8 years (median, 6.5; range, 2-36.4). Eighty-two patients
(26%) presented with lymph node recurrence (LR). Multivariate analyses showed
that LN metastases with extracapsular extension and the LN ratio (ratio between
the number of N1 and number of resected LN) in the lateral compartment were
independent predictors of recurrent disease. The median time to reoperation was
19 months (range, 3-173), with 79% of reoperations occurring within 2 years after
the initial thyroidectomy. Reoperations for LR (75 patients) were performed in
76% of the patients with a focused minimal access approach or selective LN
dissection. After curative reoperative surgery for recurrence, complications
occurred in 6 patients (8%), including a 1% permanent complication rate.
CONCLUSION: Extranodal extension of LN metastases and the LN ratio in the lateral
compartment are prognostic factors for recurrence. In most cases, reoperation for
LR can be performed with a focused minimal access approach, with a low morbidity
rate.
PMID- 26435442
TI - Discussion.
PMID- 26435443
TI - Discussion.
PMID- 26435444
TI - Facilitators and barriers of implementing enhanced recovery in colorectal surgery
at a safety net hospital: A provider and patient perspective.
AB - BACKGROUND: Enhanced Recovery After Surgery (ERAS) pathways are known to decrease
complications and duration of stay in colorectal surgery patients. However, it is
unclear whether an ERAS pathway would be feasible and effective at a safety-net
hospital. The aim of this study was to identify local barriers and facilitators
before the adoption of an ERAS pathway for patients undergoing colorectal
operations at a safety-net hospital. METHODS: Semistructured interviews were
conducted to assess the perceived barriers and facilitators before ERAS adoption.
Stratified purposive sampling was used. Interviews were audiotaped, transcribed
verbatim, and analyzed using content analysis. Analytic and investigator
triangulation were used to establish credibility. RESULTS: Interviewees included
8 anesthesiologists, 5 surgeons, 6 nurses, and 18 patients. Facilitators
identified across the different medical professions were (1) feasibility and
alignment with current practice, (2) standardization of care, (3) smallness of
community, (4) good teamwork and communication, and (5) caring for patients. The
barriers were (1) difficulty in adapting to change, (2) lack of coordination
between different departments, (3) special needs of a highly comorbid and
socioeconomically disadvantaged patient population, (4) limited resources, and
(5) rotating residents. Facilitators identified by the patients were (1)
welcoming a speedy recovery, (2) being well-cared for and satisfied with
treatment, (3) adequate social support, (4) welcoming early mobilization, and (5)
effective pain management. The barriers were (1) lack of quiet and private space,
(2) need for more patient education and counseling, and (3) unforeseen
complications. CONCLUSION: Although limited hospital resources are perceived as a
barrier to ERAS implementation at a safety-net hospital, there is strong support
for such pathways and multiple factors were identified that may facilitate
change. Inclusion of patient perspectives is critical to identifying challenges
and facilitators to implementing ERAS changes focused on optimizing patient
perioperative health and outcomes.
PMID- 26435445
TI - Defining competencies for safe thyroidectomy: An international Delphi consensus.
AB - BACKGROUND: Current methods for teaching and assessing competencies that
characterize expert intraoperative performance are inconsistent, subjective, and
lack standardization. This mixed-methods study was designed to define and
establish expert consensus on the most important competencies required to perform
a thyroidectomy safely. METHODS: Cognitive task analyses for thyroidectomy were
performed with semistructured interviews of experts in thyroid surgery. Verbal
data were transcribed verbatim, coded, and categorized according to themes that
were synthesized into a list of items. Once qualitative data reached saturation,
26 experts were invited to complete 2-round online Delphi surveys to rank each
item on a Likert scale of importance (1-7). Consensus was predefined as a
Cronbach's alpha >= 0.80. RESULTS: Sixty items were synthesized from 5 interviews
and categorized into 8 sections: preparation (n = 8), incision/exposure (n = 11),
general considerations (n = 4), middle thyroid vein (n = 1), superior pole (n =
5), inferior pole (n = 5), posterolateral dissection (n = 19), and closure (n =
7). Eighteen (69%) experts from 3 countries participated in the Delphi survey.
Consensus was achieved after 2 voting rounds (Cronbach's alpha = 0.95). Greatest
weighted sections included "Superior Pole Dissection" and "Posterolateral
Dissection." CONCLUSION: Consensus was achieved on defining the most important
competencies for safe thyroidectomy. This blueprint serves as the basis for
instructional design and objective assessment tools to evaluate performance.
PMID- 26435446
TI - Transition State Gauche Effects Control the Torquoselectivities of the
Electrocyclizations of Chiral 1-Azatrienes.
AB - Hsung et al. have reported a series of torquoselective electrocyclizations of
chiral 1-azahexa-1E,3Z,5E-trienes that yield functionalized dihydropyridines. To
understand the origins of the torquoselectivities of these
azaelectrocyclizations, we modeled these electrocyclic ring closures using the
M06-2X density functional. A new stereochemical model that rationalizes the
observed 1,2 stereoinduction emerges from these computations. This model is an
improvement and generalization of the "inside-alkoxy" model used to rationalize
stereoselectivities of the 1,3-dipolar cycloaddition of chiral allyl ethers and
emphasizes a stabilizing hyperconjugative effect, which we have termed a
transition state gauche effect. This stereoelectronic effect controls the
conformational preferences at the electrocyclization transition states, and only
in one of the allowed disrotatory electrocyclization transition states is the
ideal stereoelectronic arrangement achieved without the introduction of a steric
clash. Computational experiments confirm the role of this effect as a
stereodeterminant since substrates with electropositive groups and
electronegative groups have different conformational preferences at the
transition state and undergo ring closure with divergent stereochemical outcomes.
This predicted reversal of stereoselectivity for the ring closures of several
silyl substituted azatrienes have been demonstrated experimentally.
PMID- 26435447
TI - Does Medial Meniscal Allograft Transplantation With the Bone-Plug Technique
Restore the Anatomic Location of the Native Medial Meniscus?
AB - BACKGROUND: Previous work has shown the importance of restoring the normal
structure of the native meniscus with meniscal allograft transplantation.
PURPOSE/HYPOTHESIS: The purpose of this study was to compare the anatomic
positions of the anterior horn and posterior horn between the preoperative medial
meniscus and the postoperative meniscal allograft after medial meniscal allograft
transplantation with the bone-plug technique. The hypothesis was that the bone
plug technique could restore the preoperative structure of the native medial
meniscus. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between
December 1999 and December 2013, a total of 59 patients (49 male, 10 female)
underwent medial meniscal allograft transplantation by use of the bone-plug
technique. The anatomic positions of both horns in the native medial meniscus and
in the meniscal allograft were measured via MRI. The percentage reference method
was used to measure the locations of both horns. RESULTS: On coronal MRI, the
mean absolute distance of the posterior horn from the lateral border of the
tibial plateau changed from 45.2 +/- 3.3 to 48.1 +/- 4.2 mm (P < .05), and the
percentage distance of the posterior horn changed from 59.6% to 63.0% (P < .05).
On sagittal MRI, the mean absolute distance of the posterior horn from the
anterior reference point changed from 40.3 +/- 3.0 to 42.0 +/- 3.5 mm (P < .05),
and the mean percentage distance of the posterior horn changed from 76.5% to
79.4% (P <.05). On coronal MRI, the mean absolute distance of the anterior horn
from the lateral border of the tibial plateau changed from 41.3 +/- 4.2 to 48.5
+/- 5.6 mm (P < .05), and the mean percentage distance of the anterior horn
changed from 54.5% to 63.8% (P < .05). On sagittal MRI, the mean absolute
distance of the anterior horn from the anterior reference point changed from 5.5
+/- 1.0 to 9.9 +/- 2.9 mm (P < .05), and the mean percentage distance of the
anterior horn changed from 10.6% to 19.0% (P < .05). CONCLUSION: Despite attempts
to place the meniscal allograft in the same position as the native meniscus, the
anatomic locations of both horns were shifted posteromedially compared with those
of the native medial meniscus. There were significant differences, attributed to
several limitations in the bone-plug technique, between the preoperative and
postoperative values of both horns. However, the posterior horn showed a location
change of <5 mm, on average, in both the coronal and sagittal planes, whereas the
anterior horn showed a location change of >= 5 mm in the coronal plane but <5 mm
in the sagittal plane.
PMID- 26435448
TI - Factors Affecting the Outcomes of Double-Bundle Medial Patellofemoral Ligament
Reconstruction for Recurrent Patellar Dislocations Evaluated by Multivariate
Analysis.
AB - BACKGROUND: Many factors are involved in causing patellar instability or
recurrent patellar dislocations. However, factors affecting the outcomes of
anatomic medial patellofemoral ligament (MPFL) reconstruction have not been fully
documented. PURPOSE: To evaluate the rate of recurrent patellar instability after
isolated MPFL reconstruction and to elucidate factors affecting the outcomes of
isolated MPFL reconstruction using multivariable statistics. STUDY DESIGN: Case
control study; Level of evidence, 3. METHODS: A total of 42 patients (44 knees)
who underwent isolated, anatomic MPFL reconstruction using a semitendinosus
autograft without any additional patellar stabilization procedures for treating
recurrent patellar dislocations were included in this study. All patients were
followed for more than 2 years; the mean follow-up period was 3.2 years (range, 2
9 years). Postoperative patellofemoral instability was diagnosed when the patient
complained of recurrent patellar subluxations or dislocations or had a positive
apprehension sign during follow-up. Preoperative radiographic findings were
obtained using plain radiography and computed tomography. Femoral tunnel
positions were assessed on postoperative radiographs. The strength of the
relationship between postoperative patellofemoral instability and potential risk
factors such as preoperative age, sex, body mass index, patellar type, sulcus
angle, congruence angle, lateral tilt angle, patellar height, tibial tubercle
trochlear groove (TT-TG) distance, degree of trochlear dysplasia, and femoral
bone tunnel position were evaluated by univariate and multivariate logistic
regression analyses. RESULTS: At follow-up, 2 knees had experienced a
redislocation (4.5%). A positive apprehension sign was still evident in 8 knees
(18.2%). Three factors, including the sulcus angle, the congruence angle, and
trochlear dysplasia, were extracted by single linear regression analysis.
Univariate logistic regression analysis showed that the sulcus angle (odds ratio
[OR], 1.11; 95% CI, 1.01-1.22; P = .04) and trochlear dysplasia (OR, 3.04; 95%
CI, 1.39-6.63; P = .01) were associated with postoperative patellofemoral
instability. Trochlear dysplasia was independently associated with postoperative
patellofemoral instability by multivariable logistic regression analysis (P <
.05). An increased TT-TG distance exerted a significant effect on the outcomes of
MPFL reconstruction, particularly in patients with type D trochlea. CONCLUSION:
Severe trochlear dysplasia is the most important predictor of residual
patellofemoral instability after isolated MPFL reconstruction. In addition, an
increased TT-TG distance affected the outcomes in patients with type D trochlea.
Additional patellar stabilization procedures should be considered for patients
with severe trochlear dysplasia and an increased TT-TG distance.
PMID- 26435449
TI - The role of vitamin A and retinoic acid receptor signaling in post-natal
maintenance of bone.
AB - Vitamin A and retinoid derivatives are recognized as morphogens that govern body
patterning and skeletogenesis, producing profound defects when in excess. In post
natal bone, both high and low levels of vitamin A are associated with poor bone
heath and elevated risk of fractures. Despite this, the precise mechanism of how
retinoids induce post-natal bone changes remains elusive. Numerous studies have
been performed to discover how retinoids induce these changes, revealing a
complex morphogenic regulation of bone through interplay of different cell types.
This review will discuss the direct and indirect effects of retinoids on
mediators of bone turnover focusing on differentiation and activity of
osteoblasts and osteoclasts and explains why some discrepancies in this field
have arisen. Importantly, the overall effect of retinoids on the skeleton is
highly site-specific, likely due to differential regulation of osteoblasts and
osteoclasts at trabecular vs. cortical periosteal and endosteal bone surfaces.
Further investigation is required to discover the direct gene targets of retinoic
acid receptors (RARs) and molecular mechanisms through which these changes occur.
A clear role for RARs in regulating bone is now accepted and the therapeutic
potential of retinoids in treating bone diseases has been established.
PMID- 26435450
TI - Complete androgen insensitivity syndrome caused by a novel splice donor site
mutation and activation of a cryptic splice donor site in the androgen receptor
gene.
AB - The androgen insensitivity syndrome is an X-linked recessive genetic disorder
characterized by resistance to the actions of androgens in an individual with a
male karyotype. We evaluated a 34-year-old female with primary amenorrhea and a
46,XY karyotype, with normal secondary sex characteristics, absence of uterus and
ovaries, intra-abdominal testis, and elevated testosterone levels. Sequence
analysis of the androgen receptor (AR) gene revealed a novel splice donor site
mutation in intron 4 (c.2173+2T>C). RT-PCR analysis showed that this mutation
resulted in the activation of a cryptic splice donor site located in the second
half of exon 4 and in the synthesis of a shorter mRNA transcript and an in-frame
deletion of 41 amino acids. This novel mutation associated with a rare mechanism
of abnormal splicing further expands the spectrum of mutations associated with
the androgen insensitivity syndrome and may contribute to the understanding of
the molecular mechanisms involved in splicing defects.
PMID- 26435452
TI - Computational analysis of liquid chromatography-tandem mass spectrometric steroid
profiling in NCI H295R cells following angiotensin II, forskolin and abiraterone
treatment.
AB - Adrenal steroid hormones, which regulate a plethora of physiological functions,
are produced via tightly controlled pathways. Investigations of these pathways,
based on experimental data, can be facilitated by computational modeling for
calculations of metabolic rate alterations. We therefore used a model system,
based on mass balance and mass reaction equations, to kinetically evaluate
adrenal steroidogenesis in human adrenal cortex-derived NCI H295R cells. For this
purpose a panel of 10 steroids was measured by liquid chromatographic-tandem mass
spectrometry. Time-dependent changes in cell incubate concentrations of steroids
including cortisol, aldosterone, dehydroepiandrosterone and their precursors -
were measured after incubation with angiotensin II, forskolin and abiraterone.
Model parameters were estimated based on experimental data using weighted least
square fitting. Time-dependent angiotensin II- and forskolin-induced changes were
observed for incubate concentrations of precursor steroids with peaks that
preceded maximal increases in aldosterone and cortisol. Inhibition of 17-alpha
hydroxylase/17,20-lyase with abiraterone resulted in increases in upstream
precursor steroids and decreases in downstream products. Derived model
parameters, including rate constants of enzymatic processes, appropriately
quantified observed and expected changes in metabolic pathways at multiple
conversion steps. Our data demonstrate limitations of single time point
measurements and the importance of assessing pathway dynamics in studies of
adrenal cortical cell line steroidogenesis. Our analysis provides a framework for
evaluation of steroidogenesis in adrenal cortical cell culture systems and
demonstrates that computational modeling-derived estimates of kinetic parameters
are an effective tool for describing perturbations in associated metabolic
pathways.
PMID- 26435451
TI - Sex differences in neurodevelopmental and neurodegenerative disorders: Focus on
microglial function and neuroinflammation during development.
AB - Several neurological conditions are associated with sex differences in prevalence
or outcome. For example, autism predominantly affects boys, depression is more
common in women, Parkinson's disease more common in men, and multiple sclerosis
in women. In the case of stroke, women have a less favorable outcome and suffer
from a more precipitous drop in health status compared to men. As a result,
treatment of such diseases is difficult and yields variable results. Despite
this, sex is rarely considered when making treatment decisions. The mechanisms
underlying sex differences in disease progression are not well understood,
however a strong link exists between different inflammation states of men and
women and their propensity to develop certain diseases. As neuroinflammation is
an important component of pathophysiology in many neurological conditions, it can
be speculated that any changes in the state of inflammation in the brain during
normal development can potentially lead to an increase in susceptibility to
neurological and neurodegenerative diseases. Microglia play a crucial role in
onset and modulation of inflammation and thus sex differences in microglial
function could explain, at least in part, differences observed in
susceptibilities and outcomes of neurological disorders in men and women.
Understanding the mechanisms behind sex differences could help develop more
targeted therapy with higher success rate, especially in diseases where sex
differences are most prominent.
PMID- 26435453
TI - Intracellular localization and dynamics of Hypericin loaded PLLA nanocarriers by
image correlation spectroscopy.
AB - The study of cell-nanoparticle interactions is an important aspect for
understanding drug delivery using nanocarriers. In this regard, advances in
fluorescence based microscopy are useful for the investigation of temporal and
spatial behavior of nanoparticles (NPs) within the intracellular environment. In
this work, we focus on the delivery of the naturally-occurring hydrophobic
photosensitizer Hypericin in human lung carcinoma A549 cells by using
biodegradable poly L-lactic acid NPs. For the first time, Hypericin containing
NPs are prepared by combining the miniemulsion technique with the solvent
evaporation method. This approach yields an efficient loading of the NPs with
Hypericin and allows for additional cargo molecules. To monitor the release of
Hypercin from the NPs, an additional fluorescent lipophilic dye Coumarin-6 is
incorporated in the NPs. Temporal and spatiotemporal image correlation
spectroscopy is used to determine the fate of the NPs carrying the potential
cargo. Both directed and non-directed motions are detected. By using image cross
correlation spectroscopy and specific fluorescent labeling of endosomes,
lysosomes and mitochondria, the dynamics of the cargo loaded NPs in association
with the organelles is studied.
PMID- 26435454
TI - Delivery strategies for treatment of age-related ocular diseases: From a
biological understanding to biomaterial solutions.
AB - Age-related ocular diseases, such as age-related macular degeneration (AMD),
diabetic retinopathy, and glaucoma, result in life-long functional deficits and
enormous global health care costs. As the worldwide population ages, vision loss
has become a major concern for both economic and human health reasons. Due to
recent research into biomaterials and nanotechnology major advances have been
gained in the field of ocular delivery. This review provides a summary and
discussion of the most recent strategies employed for the delivery of both drugs
and cells to the eye to treat a variety of age-related diseases. It emphasizes
the current challenges and limitations to ocular delivery and how the use of
innovative materials can overcome these issues and ultimately provide treatment
for age-related degeneration and regeneration of lost tissues. This review also
provides critical considerations and an outlook for future studies in the field
of ophthalmic delivery.
PMID- 26435457
TI - Paratesticular Rhabdomyosarcoma Presenting With a Giant Abdominoscrotal Hydrocele
in a Toddler.
AB - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in infants and
children. Paratesticular RMS accounts for approximately 7% of all RMSs. It
commonly presents as a painless scrotal mass, which is usually distinct from the
testis. We report an unusual case of paratesticular RMS presenting with a giant
abdominoscrotal hydrocele in a toddler. To the best of our knowledge, this is the
first case of paratesticular RMS presenting with an abdominoscrotal hydrocele.
PMID- 26435456
TI - Inter-polyelectrolyte nano-assembly induces folding and activation of functional
peptides.
AB - Insufficient solubility, fragile folding structure and short half-life frequently
hamper use of peptides as biological reagents or therapies. To enhance the
peptide function, the effect of complexation of the peptides with ionic graft
copolymers with water-soluble graft chains was tested in this study. Amphiphilic
anionic peptide E5 acquires membrane disrupting activity at acidic pH due to
folding from the random coil state to an ordered alpha-helical structure.
Aggregation and imprecise folding of the peptide limited membrane disrupting
activity of the peptide. In the presence of a cationic graft copolymer, E5 and
its analogs adopted an ordered conformation without aggregation. The mixture of
the peptides and the copolymer functioned more efficiently than peptide alone at
not only acidic pH but also neutral pH at which the peptide alone had no
activity. Similarly, a cationic peptide was successfully folded and activated by
an anionic graft copolymer. Thus, our analysis indicated that spontaneous nano
assembly of ionic peptides with graft copolymers having opposite ionic charges
triggers the folding of peptides without loss of solubility, leading to enhanced
bioactivity.
PMID- 26435458
TI - Adult Pleomorphic Juxtaglomerular Cell Tumor.
AB - A 40-year-old male with chronic hypertension since his teens presented to the
emergency department following a motor vehicle collision. Computed tomography
scan demonstrated an incidental 1.8-cm renal mass. Partial nephrectomy revealed a
vascular tumor with predominantly monomorphic epithelioid cells arranged in
sheets and trabeculae with foci of nuclear pleomorphism. Tumor cells were
positive for vimentin, CD34, and c-KIT. Juxtaglomerular cell tumor is a rare,
benign neoplasm typically found in young adults. Pleomorphism is uncommon and, in
combination with older age at diagnosis, can lead to an inaccurate malignant
diagnosis. Immunohistochemistry and clinical history helps in correctly
diagnosing this benign entity.
PMID- 26435459
TI - Value of transverse relaxometry difference methods for iron in human brain.
AB - PURPOSE: To investigate the brain iron dependence of transverse relaxation rate
difference methods derived from spin echo and gradient echo measurements from two
field strengths. METHODS: Transverse relaxation rates R2 and R2(*) were measured
in human brain in 17 healthy subjects at 1.5T and 4.7T using multi-slice,
multiecho spin echo and gradient echo sequences. R2 quantification used
stimulated echo compensation and R2(*) quantification used linear background
gradient correction at 4.7T only. Subtraction of R2 from R2(*) within each field
strength yielded R2('), and R2 subtraction across fields yielded Field Dependent
R2 Increase (FDRI). All transverse relaxation measures were then correlated with
published post-mortem iron concentrations using linear regression analysis.
Regional differences were tested using paired t-tests. Phantom measurements of
FDRI were also performed. RESULTS: In deep grey matter, all transverse relaxation
rates (R2, R2(*), R2(')) at both 1.5T and 4.7T, and FDRI had moderate to strong
correlations (r>0.71, p<0.0001) with estimated non-heme iron. The 4.7T methods
and FDRI had higher correlations (r>0.9) than 1.5T measures. R2, R2(*), R2' at
4.7T and FDRI had slopes 0.49, 1.96, 1.48 and 0.33 [s(-1)/mg Fe/100g wt. tissue]
and intercepts 14.40, 16.87, 2.47 and 3.21 [s(-1)] respectively. Even though FDRI
yielded a zero intercept in phantom, in vivo FDRI was found to be ineffective at
fully removing non-iron contributions and yielded a large intercept. The slope
for R2(') was 3.4 times greater at 4.7T than 1.5T. For white matter fiber tracts
oriented predominantly perpendicular versus parallel to B0, R2(') increased by
~50% at 4.7T and ~30% at 1.5T, while R2 and FDRI in white matter was insensitive
to its orientation with respect to B0. CONCLUSION: The transverse relaxation
difference methods FDRI and R2(') at 4.7T had high correlations to predicted iron
content similar to R2 and R2(*) at 4.7T. Although R2(') had smaller y-intercept
with estimated iron concentration than FDRI, in white matter R2(') demonstrated
strongest dependence on fiber orientation with respect to B0. These results
suggest that for brain iron correlation, there is minimal value of transverse
difference methods over a single R2(*) measurement at highest available field,
which was 4.7T.
PMID- 26435460
TI - Ultrashort echo (UTE) versus pointwise encoding time reduction with radial
acquisition (PETRA) sequences at 3 Tesla for knee meniscus: A comparative study.
AB - PURPOSE: The purposes of this study were to (1) correlate the ultrashort echo
time (TE) signal intensity of the pointwise encoding time reduction with radial
acquisition (PETRA) sequence with that of the ultrashort echo (UTE) sequence
using in vivo meniscal ultrashort TE imaging of the knee with a 3-Tesla (3T)
clinical magnetic resonance imaging (MRI) scanner and (2) compare the two
ultrashort TE sequences in three groups of patients with normal, degenerated, and
torn knee menisci. MATERIALS AND METHODS: Following institutional review board
approval, we analyzed 47 knee MRIs of 46 patients who presented with knee pain
and underwent knee MRIs, including both the prototype 3D PETRA sequence knee MRI
(TE: 70MUs) and the prototype 3D UTE sequence (TE: 70 MUs) using a 3T MRI scanner
(MAGNETOM Trio, Siemens, Erlangen, Germany). The study group was classified into
three subgroups: (1) normal meniscus on conventional MRI, with no positive
meniscus-related physical examination on medical records; (2) meniscal
degeneration; and (3) meniscal tear. For quantitative assessment, the mean signal
intensities inside user-drawn regions of interest (ROIs) for each image set were
drawn on the medical menisci as well as on the bone marrow of medical femoral
condyle. For statistical analyses, the Pearson correlation test was used for
correlation of the ultrashort TE signal intensity on the UTE and the PETRA
sequences, and one-way ANOVA with post-hoc analysis using the Scheffe test was
conducted to compare groups. RESULTS: The correlation test showed moderate
correlation between the mean signal intensity values of the two ultrashort TE
sequences (Pearson's coefficient: 0.4817; P<0.05; 95% CI: 0.3113-0.6221). The
normalized mean signal intensity values were lower for patients with meniscal
degeneration and tear on both the PETRA and the UTE images. The PETRA images
showed the significantly difference between normal and tear groups and between
degeneration and normal groups (P<0.05) whereas the UTE images showed
significantly difference between normal and tear groups (P<0.05). CONCLUSION:
Both the PETRA sequence and the UTE sequence can visualize the short T2 tissue.
We demonstrated that there was significantly lower signal intensity on the
ultrashort TE UTE and the PETRA images of patients with meniscal tear.
PMID- 26435455
TI - Targeted endothelial nanomedicine for common acute pathological conditions.
AB - Endothelium, a thin monolayer of specialized cells lining the lumen of blood
vessels is the key regulatory interface between blood and tissues. Endothelial
abnormalities are implicated in many diseases, including common acute conditions
with high morbidity and mortality lacking therapy, in part because drugs and drug
carriers have no natural endothelial affinity. Precise endothelial drug delivery
may improve management of these conditions. Using ligands of molecules exposed to
the bloodstream on the endothelial surface enables design of diverse targeted
endothelial nanomedicine agents. Target molecules and binding epitopes must be
accessible to drug carriers, carriers must be free of harmful effects, and
targeting should provide desirable sub-cellular addressing of the drug cargo. The
roster of current candidate target molecules for endothelial nanomedicine
includes peptidases and other enzymes, cell adhesion molecules and integrins,
localized in different domains of the endothelial plasmalemma and differentially
distributed throughout the vasculature. Endowing carriers with an affinity to
specific endothelial epitopes enables an unprecedented level of precision of
control of drug delivery: binding to selected endothelial cell phenotypes,
cellular addressing and duration of therapeutic effects. Features of nanocarrier
design such as choice of epitope and ligand control delivery and effect of
targeted endothelial nanomedicine agents. Pathological factors modulate
endothelial targeting and uptake of nanocarriers. Selection of optimal binding
sites and design features of nanocarriers are key controllable factors that can
be iteratively engineered based on their performance from in vitro to pre
clinical in vivo experimental models. Targeted endothelial nanomedicine agents
provide antioxidant, anti-inflammatory and other therapeutic effects unattainable
by non-targeted counterparts in animal models of common acute severe human
disease conditions. The results of animal studies provide the basis for the
challenging translation endothelial nanomedicine into the clinical domain.
PMID- 26435461
TI - Ca2+ influx through L-type Ca2+ channels and Ca2+-induced Ca2+ release regulate
cAMP accumulation and Epac1-dependent ERK 1/2 activation in INS-1 cells.
AB - We previously reported that INS-1 cells expressing the intracellular II-III loop
of the L-type Ca(2+) channel Cav1.2 (Cav1.2/II-III cells) are deficient in Ca(2+)
induced Ca(2+) release (CICR). Here we show that glucose-stimulated ERK 1/2
phosphorylation (GSEP) is slowed and reduced in Cav1.2/II-III cells compared to
INS-1 cells. This parallels a decrease in glucose-stimulated cAMP accumulation
(GS-cAMP) in Cav1.2/II-III cells. Influx of Ca(2+) via L-type Ca(2+) channels and
CICR play roles in both GSEP and GS-cAMP in INS-1 cells since both are inhibited
by nicardipine or ryanodine. Further, the Epac1-selective inhibitor CE3F4
abolishes glucose-stimulated ERK activation in INS-1 cells, as measured using the
FRET-based sensor EKAR. The non-selective Epac antagonist ESI-09 but not the
Epac2-selective antagonist ESI-05 nor the PKA antagonist Rp-cAMPs inhibits GSEP
in both INS-1 and Cav1.2/II-III cells. We conclude that L-type Ca(2+) channel
dependent cAMP accumulation, that's amplified by CICR, activates Epac1 and drives
GSEP in INS-1 cells.
PMID- 26435462
TI - Controversies in guidelines for the control of multidrug-resistant Gram-negative
bacteria in EU countries.
AB - The various guidelines that are available for multidrug-resistant Gram-negative
bacteria are useful, and contain broad areas of agreement. However, there are
also important areas of controversy between the guidelines in terms of the
details of applying contact precautions, single-room isolation and active
surveillance cultures, differences in the approach to environmental cleaning and
disinfection, and whether or not to perform staff and patient cohorting,
healthcare worker screening or patient decolonization. The evidence-base is
extremely limited and further research is urgently required to inform an evidence
based approach to multidrug-resistant Gram-negative bacteria prevention and
control.
PMID- 26435463
TI - Membrane protein structures without crystals, by single particle electron
cryomicroscopy.
AB - It is an exciting period in membrane protein structural biology with a number of
medically important protein structures determined at a rapid pace. However, two
major hurdles still remain in the structural biology of membrane proteins. One is
the inability to obtain large amounts of protein for crystallization and the
other is the failure to get well-diffracting crystals. With single particle
electron cryomicroscopy, both these problems can be overcome and high-resolution
structures of membrane proteins and other labile protein complexes can be
obtained with very little protein and without the need for crystals. In this
review, I highlight recent advances in electron microscopy, detectors and
software, which have allowed determination of medium to high-resolution
structures of membrane proteins and complexes that have been difficult to study
by other structural biological techniques.
PMID- 26435464
TI - Effect of dietary manganese on antioxidant status and expression levels of heat
shock proteins and factors in tissues of laying broiler breeders under normal and
high environmental temperatures.
AB - To investigate the effect of Mn on antioxidant status and expression levels of
heat-shock proteins/factors in tissues of laying broiler breeders subjected to
heat challenge, we used a completely randomised design (n 6) with a factorial
arrangement of 2 environmental temperatures (normal, 21 (sem 1) degrees C and
high, 32 (sem 1) degrees C)*3 dietary Mn treatments (an Mn-unsupplemented basal
diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn
sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions
(P>0.10) between environmental temperature and dietary Mn in all of the measured
indices. High temperature decreased (P<0.003) Mn content, and also tended
(P=0.07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the
liver and heart. However, an increased manganese superoxide dismutase (MnSOD)
activity (P<0.05) and a slight increase of malondialdehyde level (P=0.06) were
detected in breast muscle. Up-regulated (P<0.05) expression levels of heat-shock
factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein
were found in all three tissues. Broiler breeders fed either iMn or oMn had
higher tissue Mn content (P<0.0001), heart MnSOD and CuZnSOD activities (P<0.01)
and breast muscle MnSOD protein levels (P<0.05), and lower (P<0.05) breast muscle
HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had
higher (P<0.03) bone Mn content than those fed iMn. These results indicate that
high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3
expression levels in tissues of laying broiler breeders. Furthermore, dietary
supplementation with Mn in either source may enhance heart antioxidant ability
and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn
appears to be more available than inorganic Mn for bone in laying broiler
breeders regardless of environmental temperatures.
PMID- 26435465
TI - A naphthalimide-based [12]aneN3 compound as an effective and real-time
fluorescence tracking non-viral gene vector.
AB - A novel bifunctional naphthalimide-based [12]aneN3 compound 1 was successfully
applied as an effective non-viral gene vector in cancer cells, the fluorescence
properties of 1 clearly demonstrated the process of cellular uptake, DNA
translocation and release based on real-time fluorescence tracking.
PMID- 26435466
TI - Structure and rheology of star polymers in confined geometries: a mesoscopic
simulation study.
AB - Mesoscopic simulations of star polymer melts adsorbed onto solid surfaces are
performed using the dissipative particle dynamics (DPD) method. A set of
parameters is developed to study the low functionality star polymers under shear.
The use of a new bond-angle potential between the arms of the star creates more
rigid chains and discriminates between different functionalities at equilibrium,
but still allows the polymers to deform appropriately under shear. The rheology
of the polymer melts is studied by calculating the kinetic friction and viscosity
and there is good agreement with experimental properties of these systems. The
study is completed with predictive simulations of star polymer solutions in an
athermal solvent.
PMID- 26435467
TI - Probing zeolites by vibrational spectroscopies.
AB - This review addresses the most relevant aspects of vibrational spectroscopies
(IR, Raman and INS) applied to zeolites and zeotype materials. Surface Bronsted
and Lewis acidity and surface basicity are treated in detail. The role of probe
molecules and the relevance of tuning both the proton affinity and the steric
hindrance of the probe to fully understand and map the complex site population
present inside microporous materials are critically discussed. A detailed
description of the methods needed to precisely determine the IR absorption
coefficients is given, making IR a quantitative technique. The thermodynamic
parameters of the adsorption process that can be extracted from a variable
temperature IR study are described. Finally, cutting-edge space- and time
resolved experiments are reviewed. All aspects are discussed by reporting
relevant examples. When available, the theoretical literature related to the
reviewed experimental results is reported to support the interpretation of the
vibrational spectra on an atomic level.
PMID- 26435468
TI - Human Cytomegalovirus and Epstein-Barr Virus Genotypes in Apical Periodontitis
Lesions.
AB - INTRODUCTION: Different genotypes of human cytomegalovirus (HCMV) and Epstein
Barr virus (EBV) possess specific pathogenic abilities because of various
interactions with the host's immune system and differences in cell tropism. The
aim of this study was to determine the distribution of HCMV and EBV genotypes in
apical periodontitis lesions in relation to their clinical and histopathologic
features. METHODS: One hundred samples of apical periodontitis lesions and 25
control samples (healthy pulp tissue) were collected. The presence of HCMV
glycoprotein B (gB) and EBV nuclear antigen-2 genotypes was analyzed by nested
polymerase chain reaction and restriction fragment length polymorphisms analysis.
RESULTS: EBV and HCMV were detected in apical periodontitis lesions at
significantly higher frequencies than in healthy pulp controls (P = .020 and P =
.020, respectively). HCMV gB type II was significantly more frequent compared
with gB type I in the examined groups (P = .036). No HCMV gB type III or IV
products were found. In both periapical lesions and controls, EBV-1 occurred more
often compared with EBV-2 (P = .001). Dual EBV and HCMV coinfection was more
frequently detected in large-size periapical lesions (P = .038). CONCLUSIONS:
Both HCMV and EBV are associated with inflammatory processes of periapical bone
destruction. HCMV gB type II and EBV-1 are the most prevalent genotypes in apical
periodontitis lesions.
PMID- 26435469
TI - Combined Effects of Growth Hormone and Mineral Trioxide Aggregate on Growth,
Differentiation, and Angiogenesis in Human Dental Pulp Cells.
AB - INTRODUCTION: The aim of this study was to evaluate the effects of growth hormone
(GH) on mineral trioxide aggregate (MTA) with regard to cell adhesion, growth,
odontoblastic differentiation, and angiogenesis in human dental pulp cells and
the underlying signal pathway mechanisms. METHODS: Cell adhesion and
proliferation were assessed by adhesion analysis and cell counting.
Differentiation was examined by alkaline phosphatase activity, alizarin red
staining, and reverse transcriptase polymerase chain reaction for marker genes.
Angiogenesis was evaluated by human umbilical vein endothelial cell migration and
capillary tube formation assays. Signaling pathways were analyzed by Western
blotting and confocal microscopy. RESULTS: Combined treatment with GH and MTA
enhanced cell adhesion, growth, alkaline phosphatase activity, calcified nodules,
expression of marker mRNAs, migration, and capillary tube formation, compared
with treatment with MTA or GH alone. In addition, GH plus MTA increased
expression of bone morphogenetic protein-2 mRNA, phosphorylation of Smad 1/5/8,
extracellular signal-regulated kinase, JNK, and p38 MAPK, and increased the
levels of the transcription factors Runx2 and Osterix, compared with MTA alone.
CONCLUSIONS: Collectively, our results demonstrate that a combination of MTA and
GH promotes cell adhesion, growth, differentiation, and angiogenesis of MTA in
human dental pulp cells via the activation of bone morphogenetic protein and MAPK
pathway.
PMID- 26435470
TI - Calcium Hydroxide versus Mineral Trioxide Aggregate for Direct Pulp Capping: A
Cost-effectiveness Analysis.
AB - INTRODUCTION: Recent evidence finds mineral trioxide aggregate (MTA) more
effective than calcium hydroxide (CH) for direct pulp capping (DPC). The present
study assessed the cost-effectiveness of MTA versus CH for DPC using a model
based simulation approach. METHODS: A mixed public/private payer perspective in
the context of German health care was adopted. We modeled a permanent molar with
a vital asymptomatic, exposed pulp treated via DPC with either MTA or CH. The
tooth was followed over the lifetime of a 20-year-old patient using Markov
models. Transition probabilities were obtained from systematically and
nonsystematically collected data. The primary health outcome was tooth retention
time. Costs for DPC were estimated via microcosting. Required personnel time for
application was estimated using a survey among German specialized and general
dentists. Material expenses were calculated based on market prices in 2015. All
other costs were derived from public and private item fee catalogues. Uncertainty
was introduced via probabilistic and univariate sensitivity analyses. RESULTS:
DPC using MTA was both more effective and less costly (52 years retention,
lifetime costs = 1368 Euro) than CH (49 years, 1527 Euro). Regardless of a
payer's willingness to pay, DPC with MTA had the higher probability of being cost
effective. The identified ranking was not affected by parameter or structural
uncertainty or heterogeneity. CONCLUSIONS: MTA was more cost-effective than CH
for DPC despite higher initial treatment costs because expensive retreatments
were avoided. Our estimates apply only on the basis of current evidence and
within the chosen health care setting. From a payer's perspective, MTA should be
used for DPC.
PMID- 26435471
TI - Editorial: Small Molecules and Peptides Targeting the Eph-Ephrin System.
PMID- 26435472
TI - Comparison of insulin degludec with insulin detemir in type 1 diabetes: a 1-year
treat-to-target trial.
AB - The long-term safety and tolerability of insulin degludec (IDeg) was compared
with that of insulin detemir (IDet), as basal treatment in participants with type
1 diabetes mellitus (T1DM). In the present multinational, 26-week core + 26-week
extension, controlled, open-label, parallel-group trial, adults with T1DM were
randomized to IDeg or IDet as basal insulin treatment combined with meal-time
bolus insulin aspart. IDeg was administered once daily, whilst IDet was
administered once or twice daily depending on patients' glycaemic control. After
1 year, IDeg provided a 33% lower rate of nocturnal hypoglycaemia compared with
IDet: estimated rate ratio (IDeg : IDet) 0.67 [95% confidence interval (CI) 0.51;
0.88]; p < 0.05. IDeg improved glycated haemoglobin after 1 year of treatment,
similarly to IDet, but IDeg also provided a significantly greater reduction in
fasting plasma glucose compared with IDet: estimated difference (IDeg - IDet)
1.11 (95% CI -1.83; -0.40) mmol/l; p < 0.05. The present study confirmed the long
term safety and tolerability profile of IDeg in patients with T1DM. IDeg provided
a lower risk of nocturnal confirmed hypoglycaemia than IDet.
PMID- 26435473
TI - Chewing-induced hypertension in afferent baroreflex failure: a sympathetic
response?
AB - NEW FINDINGS: What is the central question of this study? Our goal was to
understand the autonomic responses to eating in patients with congenital afferent
baroreflex failure, by documenting changes in blood pressure and heart rate with
chewing, swallowing and stomach distension. What is the main finding and its
importance? Patients born with lesions in the afferent baroreceptor pathways have
an exaggerated pressor response to food intake. This appears to be a
sympathetically mediated response, triggered by chewing, that occurs
independently of swallowing or distension of the stomach. The chewing-induced
pressor response may be useful as a counter-manoeuvre to prevent orthostatic
hypotension in these patients. Familial dysautonomia (FD) is a rare genetic
disease with extremely labile blood pressure resulting from baroreflex
deafferentation. Patients have marked surges in sympathetic activity, frequently
surrounding meals. We conducted an observational study to document the autonomic
responses to eating in patients with FD and to determine whether sympathetic
activation was caused by chewing, swallowing or stomach distension. Blood
pressure and R-R intervals were measured continuously while chewing gum (n = 15),
eating (n = 20) and distending the stomach by percutaneous endoscopic gastrostomy
tube feeding (n = 9). Responses were compared with those of normal control
subjects (n = 10) and of patients with efferent autonomic failure (n = 10) who
have chronically impaired sympathetic outflow. In patients with FD, eating was
associated with a marked but transient pressor response (P < 0.0001) and
additional signs of sympathetic activation, including tachycardia, diaphoresis
and flushing of the skin. Chewing gum evoked a similar increase in blood pressure
that was higher in patients with FD than in control subjects (P = 0.0001), but
was absent in patients with autonomic failure. In patients with FD, distending
the stomach by percutaneous endoscopic gastrostomy tube feeding failed to elicit
a pressor response. The results provide indirect evidence that chewing triggers
sympathetic activation. The increase in blood pressure is exaggerated in patients
with FD as a result of blunted afferent baroreceptor signalling. The chewing
pressor response may be useful as a counter-manoeuvre to raise blood pressure and
prevent symptomatic orthostatic hypotension in patients with FD.
PMID- 26435474
TI - Memory enhancement by Tamoxifen on amyloidosis mouse model.
AB - Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) used in the
treatment of breast cancer. Earlier studies show its neuroprotection via
regulating apoptosis, microglial functions, and synaptic plasticity. TMX also
showed memory enhancement in ovariectomized mice, and protection from amyloid
induced damage in hippocampal cell line. These reports encouraged us to explore
the role of TMX in relevance to Alzheimer's disease (AD). We report here, the
effect of TMX treatment a) on memory, and b) levels of neurotransmitters
(acetylcholine (ACh) and dopamine (DA)) in breeding-retired-female mice injected
with beta amyloid1-42 (Abeta1-42). Mice were treated with TMX (10mg/kg, i.p.) for
15 days. In Morris water maze test, the TMX treated mice escape latency decreased
during training trials. They also spent longer time in the platform quadrant on
probe trial, compared to controls. In Passive avoidance test, TMX treated mice
avoided stepping on the shock chamber. This suggests that TMX protects memory
from Abeta induced toxicity. In frontal cortex, ACh was moderately increased,
with TMX treatment. In striatum, dopamine was significantly increased, 3,4
dihydroxyphenylacetic acid (DOPAC) level and DOPAC/DA ratio was decreased post
TMX treatment. Therefore, TMX enhances spatial and contextual memory by reducing
dopamine metabolism and increasing ACh level in Abeta1-42 injected-breeding
retired-female mice.
PMID- 26435475
TI - Thyroid hormone status affects expression of daily torpor and gene transcription
in Djungarian hamsters (Phodopus sungorus).
AB - Thyroid hormones (TH) play a key role in regulation of seasonal as well as acute
changes in metabolism. Djungarian hamsters (Phodopus sungorus) adapt to winter by
multiple changes in behaviour and physiology including spontaneous daily torpor,
a state of hypometabolism and hypothermia. We investigated effects of systemic TH
administration and ablation on the torpor behaviour in Djungarian hamsters
adapted to short photoperiod. Hyperthyroidism was induced by giving T4 or T3 and
hypothyroidism by giving methimazole (MMI) and sodium perchlorate via drinking
water. T3 treatment increased water, food intake and body mass, whereas MMI had
the opposite effect. Continuous recording of body temperature revealed that low
T3 serum concentrations increased torpor incidence, lowered Tb and duration,
whereas high T3 serum concentrations inhibited torpor expression. Gene expression
of deiodinases (dio) and uncoupling proteins (ucp) were analysed by qPCR in
hypothalamus, brown adipose tissue (BAT) and skeletal muscle. Expression of dio2,
the enzyme generating T3 by deiodination of T4, and ucps, involved in
thermoregulation, indicated a tissue specific response to treatment. Torpor per
se decreased dio2 expression irrespective of treatment or tissue, suggesting low
intracellular T3 concentrations during torpor. Down regulation of ucp1 and ucp3
during torpor might be a factor for the inhibition of BAT thermogenesis.
Hypothalamic gene expression of neuropeptide Y, propopiomelanocortin and
somatostatin, involved in feeding behaviour and energy balance, were not affected
by treatment. Taken together our data indicate a strong effect of thyroid
hormones on torpor, suggesting that lowered intracellular T3 concentrations in
peripheral tissues promote torpor.
PMID- 26435476
TI - "Retronychia--clinical and pathophysiological aspects".
AB - Retronychia represents proximal ingrowth of the nail that occurs when the nail
embeds backwards into the proximal nail fold. It is suspected when there is a
persistent paronychia, particularly in the setting of trauma. Important clinical
criteria for diagnosis are inflammation of the proximal nail fold, granulation
tissue emerging from under the nail fold, thickening of the proximal portion of
the nail plate and interruption of nail growth. The condition is rarely diagnosed
and often misinterpreted, and is therefore unnecessarily treated with systemic
antibiotics and antifungals. Avulsion of the nail confirms the diagnosis and it
is the curative treatment. Conservative treatment with an adhesive technique is a
valid option in early cases. We report 20 cases of retronychia diagnosed in our
department between 2010 and 2013.
PMID- 26435477
TI - Suppression of CD300A inhibits the growth of diffuse large B-cell lymphoma.
AB - CD300A is a type I transmembrane receptor protein which has shown inhibitory
effects on B-cell receptor-mediated signals. In an analysis of public dataset, we
found that CD300A mRNA levels were inversely correlated with the overall survival
time of patients with diffuse large B-cell lymphoma (DLBCL). To decipher the role
of CD300A in DLBCL, we knocked down the expression levels of CD300A in DLBCL
cells and found that decreasing levels of CD300A significantly inhibited cell
proliferation of OCI-Ly01, Farage, and SUDHL-4 cells, but not of VAL, OCI-Ly10,
or SUDHL-8 cells. Mechanistically, reduced expression of CD300A resulted in a
marked attenuation of AKT phosphorylation, a key molecular event in
tumorigenesis, in OCI-Ly01, Farage, and SUDHL-4 cells. Pharmacologic inhibition
of PI3K displayed a similar inhibitory effect on cell proliferation. Furthermore,
using a xenograft animal model, we found that decreasing levels of CD300A in OCI
Ly01 and Farage cells significantly inhibited tumor formation in vivo.
Collectively, our results suggested an oncogenic role of CD300A in DLBCL which
could serve as a potential biomarker and therapeutic target for this malignant
disease.
PMID- 26435479
TI - Rapid targeted somatic mutation analysis of solid tumors in routine clinical
diagnostics.
AB - Tumor genotyping is an essential step in routine clinical practice and pathology
laboratories face a major challenge in being able to provide rapid, sensitive and
updated molecular tests. We developed a novel mass spectrometry multiplexed
genotyping platform named PentaPanel to concurrently assess single nucleotide
polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes,
KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To
both evaluate and validate the PentaPanel performance, we investigated 1025 tumor
specimens of 6 different cancer types (carcinomas of colon, lung, breast,
pancreas, and biliary tract, and melanomas), systematically addressing
sensitivity, specificity, and reproducibility of our platform. Sanger sequencing
was also performed for all the study samples. Our data showed that PentaPanel is
a high throughput and robust tool, allowing genotyping for targeted therapy
selection of 10 patients in the same run, with a practical turnaround time of 2
working days. Importantly, it was successfully used to interrogate different DNAs
isolated from routinely processed specimens (formalin-fixed paraffin embedded,
frozen, and cytological samples), covering all the requirements of clinical
tests. In conclusion, the PentaPanel platform can provide an immediate, accurate
and cost effective multiplex approach for clinically relevant gene mutation
analysis in many solid tumors and its utility across many diseases can be
particularly relevant in multiple clinical trials, including the new basket trial
approach, aiming to identify appropriate targeted drug combination strategies.
PMID- 26435478
TI - Apigenin blocks IKKalpha activation and suppresses prostate cancer progression.
AB - IKKalpha has been implicated as a key regulator of oncogenesis and driver of the
metastatic process; therefore is regarded as a promising therapeutic target in
anticancer drug development. In spite of the progress made in the development of
IKK inhibitors, no potent IKKalpha inhibitor(s) have been identified. Our
multistep approach of molecular modeling and direct binding has led to the
identification of plant flavone apigenin as a specific IKKalpha inhibitor. Here
we report apigenin, in micro molar range, inhibits IKKalpha kinase activity,
demonstrates anti-proliferative and anti-invasive activities in functional cell
based assays and exhibits anticancer efficacy in experimental tumor model. We
found that apigenin directly binds with IKKalpha, attenuates IKKalpha kinase
activity and suppresses NF-KB/p65 activation in human prostate cancer PC-3 and
22Rv1 cells much more effectively than IKK inhibitor, PS1145. We also showed that
apigenin caused cell cycle arrest similar to knockdown of IKKalpha in prostate
cancer cells. Studies in xenograft mouse model indicate that apigenin feeding
suppresses tumor growth, lowers proliferation and enhances apoptosis. These
effects correlated with inhibition of p-IKKalpha, NF-KB/p65, proliferating cell
nuclear antigen and increase in cleaved caspase 3 expression in a dose-dependent
manner. Overall, our results suggest that inhibition of cell proliferation,
invasiveness and decrease in tumor growth by apigenin are mediated by its ability
to suppress IKKalpha and downstream targets affecting NF-KB signaling pathways.
PMID- 26435480
TI - Development and validation of a pretreatment prognostic index to predict death
and lung metastases in extremity osteosarcoma.
AB - BACKGROUND: To develop a prognostic index to predict the 5-year overall survival
(OS) and 5-year lung metastasis-free survival (LMFS) of patients with extremity
osteosarcoma at the time of diagnosis. METHODS: We retrospectively evaluated 454
patients with extremity osteosarcoma at our center from 2005 to 2013. The cohort
was randomly divided into training and validation sets. The association of
potential risk factors with OS and LMFS was assessed by Cox proportional hazards
analysis in the training set, and a prognostic index was created according to
scores that were proportional to a regression coefficient for each factor. This
prognostic index was assessed in the validation set. RESULTS: For the 5-year OS,
5 independent prognostic factors were identified: tumor size, Enneking stage,
pretreatment platelet, alkaline phosphatase(ALP), and neutrophils. The
multivariate Cox model identified tumor size, pretreatment platelets, ALP, and
neutrophils as associated with the 5-year LMFS. A prognostic index for death and
lung metastases was calculated. Three risk groups were defined for each survival
point: low, intermediate, and high risk for the 5-year OS; low, intermediate, and
high risk for the 5-year LMFS. The C statistic for the 5-year OS was 0.723 in the
training set and 0.710 in the validation set. The C statistic for the 5-year LMFS
was 0.661 and 0.693 respectively. CONCLUSIONS: This prognostic index is based on
routine tests and characteristics of extremity osteosarcoma patients and is a
useful predictor of OS and lung metastases. This index could be applied to
clinical practice and trials for individualized risk-adapted therapies.
PMID- 26435482
TI - Human Rights, Humanitarianism, and State Violence: Medical Documentation of
Torture in Turkey.
AB - State authorities invested in developing official expert discourses and practices
to deny torture in post-1980 coup d'etat Turkey. Documentation of torture was
therefore crucial for the incipient human rights movement there in the 1980s.
Human rights physicians used their expertise not only to treat torture victims
but also to document torture and eventually found the Human Rights Foundation of
Turkey (HRFT) in 1990. Drawing on an ethnographic and archival research at the
HRFT, this article examines the genealogy of anti-torture struggles in Turkey and
argues that locally mediated intimacies and/or hostilities between victims of
state violence, human rights physicians, and official forensics reveal the
limitations of certain universal humanitarian and human rights principles. It
also shows that locally mediated long-term humanitarian encounters around the
question of political violence challenge forensic denial of violence and remake
the legitimate levels of state violence.
PMID- 26435481
TI - HER2 as a novel therapeutic target for cervical cancer.
AB - Surgery and radiation are the current standard treatments for cervical cancer.
However, there is no effective therapy for metastatic or recurrent cases,
necessitating the identification of therapeutic targets. In order to create
preclinical models for screening potential therapeutic targets, we established 14
patient-derived xenograft (PDX) models of cervical cancers using subrenal
implantation methods. Serially passaged PDX tumors retained the histopathologic
and genomic features of the original tumors. Among the 9 molecularly profiled
cervical cancer patient samples, a HER2-amplified tumor was detected by array
comparative genomic hybridization and targeted next-generation sequencing. We
confirmed HER2 overexpression in the tumor and serially passaged PDX. Co
administration of trastuzumab and lapatinib in the HER2-overexpressed PDX
significantly inhibited tumor growth compared to the control. Thus, we
established histopathologically and genomically homologous PDX models of cervical
cancer using subrenal implantation. Furthermore, we propose HER2 inhibitor-based
therapy for HER2-amplified cervical cancer refractory to conventional therapy.
PMID- 26435483
TI - Dual fluorescent deoxyguanosine mimics for FRET detection of G-quadruplex
folding.
AB - Replacement of deoxyguanosine (dG) nucleobases within G-tetrads of G-quadruplex
folding oligonucleotides with donor (D)/acceptor (A) fluorescent 8aryldG residues
provides diagnostic FRET signalling for G-quadruplex detection.
PMID- 26435484
TI - New High- and Low-Temperature Phase Changes of ZIF-7: Elucidation and Prediction
of the Thermodynamics of Transitions.
AB - We have found that the 3D zeolitic imidazolate framework ZIF-7 exhibits far more
complex behavior in response to the adsorption of guest molecules and changes in
temperature than previously thought. We believe that this arises from the
existence of different polymorphs and different types of adsorption sites. We
report that ZIF-7 undergoes a displacive, nondestructive phase change upon
heating to above ~700 degrees C in vacuum, or to ~500 degrees C in CO2 or N2.
This is the first example of a temperature-driven phase change in 3D ZIF
frameworks. We predicted the occurrence of the high-temperature transition on the
basis of thermodynamic arguments and analyses of the solid free-energy
differences obtained from CO2 and n-butane adsorption isotherms. In addition, we
found that ZIF-7 exhibits complex behavior in response to the adsorption of CO2
manifesting in double transitions on adsorption isotherms and a doubling of the
adsorption capacity. We report adsorption microcalorimetry, molecular
simulations, and detailed XRD investigations of the changes in the crystal
structure of ZIF-7. Our results highlight mechanistic details of the phase
transitions in ZIF-7 that are driven by adsorption of guest molecules at low
temperature and by entropic effects at high temperature. We derived a phase
diagram of CO2 in ZIF-7, which exhibits surprisingly complex re-entrant behavior
and agrees with our CO2 adsorption measurements over a wide range of temperatures
and pressures. We predicted phase diagrams of CH4, C3H6, and C4H10. Finally, we
modeled the temperature-induced transition in ZIF-7 using molecular dynamics
simulations in the isobaric-isothermal ensemble, confirming our thermodynamic
arguments.
PMID- 26435485
TI - Quantitative analysis of Cryptosporidium growth in in vitro culture--the impact
of parasite density on the success of infection.
AB - Cryptosporidium is an important waterborne pathogen for which no treatment or
vaccination is available. This study set out to quantify DNA replication of
Cryptosporidium parvum in vitro. Cryptosporidium DNA could be detected at up to
60 % of input level in both host-cell-free and host cell containing cultures 6
days after infection with living sporozoites, but was lost within 2 days in
cultures inoculated with UV-inactivated sporozoites. Total DNA increased between
days 2 and 6, evidence of successful DNA replication in both cell-free and host
cell-containing cultures. Overall however, only a small fraction (up to 5 %) of
parasite DNA could be found associated with host cells or bound to plastic of the
cell-free cultures, and the majority of parasite DNA was present in the cell
culture medium, separable by simple decantation. After 2 days, in host-cell
containing cultures, the parasite DNA could be concentrated by slow
centrifugation, suggesting that it was associated with intact parasite cells, but
at 6 days, the majority could not be centrifuged and is therefore thought to have
represented copies associated with dead and degraded parasites. In cell-free
cultures and in larger plates, the majority of DNA was in this form. Performance
of the parasite was best in small culture plates, and least in the largest plate
sizes. We interpret these results as suggesting that Cryptosporidium sporozoites
first bind to the host cell monolayer or to the plasticware, but then by 2 days,
there has been a substantial release of parasites back into the medium. Host-cell
free cultures also supported modest replication and may have represented DNA
synthesis in cells beginning merogony. The role of the host cells is unclear, as
so much of the parasite DNA is released into the medium. Host cells may provide a
feeder role, conditioning the medium for Cryptosporidium development.
PMID- 26435486
TI - Robot-assisted partial nephrectomy with intracorporeal renal hypothermia using
ice slush: step-by-step technique and matched comparison with warm ischaemia.
AB - OBJECTIVES: To outline our step-by-step technique for intracorporeal renal
cooling during robot-assisted partial nephrectomy (RAPN). PATIENTS AND METHODS:
Patient selection was performed during a preoperative clinic visit. Cases where
we estimated during preoperative assessment that warm ischaemia time would be >30
min, as determined by whether the patient had a complex renal mass, were
selected. The special equipment required for this procedure includes an Ecolab
Hush Slush machine (Microtek Medical Inc., Columbus, MS, USA) a Mon-a-therm
needle thermocouple device (Covidien, Mansfield, MA, USA) and six modified 20-mL
syringes. Patients are arranged in a 60 degrees modified flank position with the
operating table flexed slightly at the level of the anterior superior iliac
spine. For the introduction of a temperature probe and ice slush, an additional
12-mm trocar is placed along the mid-axillary line beneath the costal margin.
Modified 10/20 mL syringes are prefilled with ice slush for instillation via an
accessory trocar. Peri-operative and 6-month functional outcomes in the cold
ischaemia group were compared with those of a cohort of patients who underwent
RAPN with warm ischaemia in a 2:1 matched fashion. Matching was performed based
on preoperative estimated glomerular filtration rate (GFR), ischaemia time and
RENAL nephrometry score. RESULTS: Strategies for successful intracorporeal renal
cooling include: (i) placement of accessory port directly over the kidney; (ii)
uniform ice consistency and modified syringes; (iii) sequential clamping of renal
artery and vein; (iv) protection of the neighbouring intestine with a
laparoscopic sponge; and (v) complete mobilization of the kidney. Kidney
temperature is monitored via a needle thermocoupler device, while core body
temperature is concurrently monitored via an oesophageal probe in real time.
Renal function was assessed by serum creatinine level, estimated GFR (eGFR) and
mercaptoacetyltriglycine (MAG-3) renal scan, peri-operatively and at 6-month
follow-up. In the separate matched analysis, cold ischaemia during RAPN was found
to be associated with a 12.9% improvement in preservation of postoperative eGFR.
No difference was seen in either group at 6-month follow-up. CONCLUSIONS: We
conclude that RAPN with intracorporeal renal hypothermia using ice slush is
technically feasible and may improve postoperative renal function in the short
term. Our technique for intracorporeal hypotheramia is cost-effective, simple and
highly reproducible.
PMID- 26435487
TI - Elevated Serum Beta-Trace Protein Levels are Associated With the Presence of
Atrial Fibrillation in Hypertension Patients.
AB - Beta-trace protein (BTP) has emerged as a novel biomarker of cardiovascular risk.
In this study, the authors aimed to assess the relationship between BTP levels
and presence of atrial fibrillation in patients who had controlled hypertension
(HTN) and normal renal function. A total of 80 controlled HTN patients with
paroxysmal atrial fibrillation (PAF) and 80 age- and sex-matched controls with
controlled HTN were enrolled. Serum BTP levels were measured by enzyme-linked
immunosorbent assay. BTP levels were found to be significantly higher in patients
with PAF (P<.001). Other parameters including mean systolic and diastolic blood
pressure values, serum creatinine levels, and glomerular filtration rate were
similar between the two groups. Along with left atrial diameter (odds ratio,
1.504; P<.001), BTP levels (odds ratio, 1.015; P<.001) were independently
associated with the presence of PAF. BTP levels were increased in controlled HTN
patients with PAF compared with controls, and this association was observed
within normal renal functions as reflected by normal glomerular filtration rate.
PMID- 26435488
TI - Dermoscopy as a diagnostic aid in a case of systemic amyloidosis with initial
presentation in skin.
PMID- 26435489
TI - Differential impact of upward and downward comparisons on diverse women's
disordered eating behaviors and body image.
AB - OBJECTIVE: Etiological models of disordered eating are limited in their
consideration of racial/ethnic differences in risk factors. Appearance
comparisons are consistent predictors of disordered eating outcomes, but research
predominantly examines these associations among White women and overlooks the
potential differential impact of upward (comparing to someone perceived as better
off) versus downward comparisons (comparing to someone perceived as worse off).
This study investigated race/ethnicity as a moderator of the associations between
upward and downward appearance comparisons and disordered eating outcomes and
body satisfaction of young adult women. METHOD: Measures of upward and downward
appearance comparisons, body satisfaction, and disordered eating were
administered to 1,014 young adult women. A multiple group (by race/ethnicity)
path analysis was estimated using maximum likelihood estimation for each
disordered eating and body satisfaction outcome, controlling for age and BMI.
RESULTS: Upward comparisons were associated with higher levels of disordered
eating behaviors and lower body satisfaction for women of all racial/ethnic
groups. Downward appearance comparisons emerged as detrimental for
Hispanic/Latina women, but were protective for Asian and White women. DISCUSSION:
Findings challenge the belief that appearance comparisons impact all women
similarly and that downward comparisons are universally protective, a position
often promulgated by clinical treatment approaches. (c) 2015 Wiley Periodicals,
Inc. (Int J Eat Disord 2016; 49:519-523).
PMID- 26435490
TI - On the effect of sodium salts on the coil-to-globule transition of poly(N
isopropylacrylamide).
AB - It has been shown that sodium salts significantly affect the temperature of the
coil-to-globule collapse transition of poly(N-isopropylacrylamide) [J. Am. Chem.
Soc., 2005, 127, 14505]. Since this phenomenon resembles the cold renaturation of
globular proteins, it can be studied by means of the theoretical approach devised
to rationalise the occurrence and the mechanism of cold denaturation [G.
Graziano, Phys. Chem. Chem. Phys., 2010, 12, 14245; Phys. Chem. Chem. Phys.,
2014, 16, 21755]. It emerges that the collapse transition is driven by the
decrease in the solvent-excluded volume in order to maximise the translational
entropy of water molecules and ions. At a given temperature, the aqueous
solutions of sodium salts have densities higher than that of water. For this
reason, the magnitude of the solvent-excluded volume effect proves to be larger,
stabilizing the globular conformations of poly(N-isopropylacrylamide). On the
other hand, two large ions, iodide and thiocyanate, are poorly hydrated and
stabilise the coil conformations of the polymer by a preferential binding
mechanism.
PMID- 26435491
TI - The role of family carers in the use of personal budgets by people with mental
health problems.
AB - Personal budgets aim to increase choice and independence for people with social
care needs but they remain underused by people with mental health problems
compared to other disability groups. The use of personal budgets may impact on
families in a variety of ways, both positive and negative. This paper draws on
interviews, undertaken in 2012-2013 with 18 family carers and 12 mental health
service users, that explored experiences of family involvement in accessing and
managing personal budgets for a person with mental health-related social care
needs. The sample was drawn from three sites across England, with additional
carers being recruited via voluntary sector networks. Our findings show that for
many people with severe mental health needs who lack motivation and confidence to
negotiate access to personal budgets, carers may provide the necessary support to
enable them to benefit from this form of social care support. We illustrate the
role carers may play in initiating, pursuing and maximising the level of support
available through personal budgets. However, some carers interviewed considered
that personal budget funding was reduced because of practitioners' assumptions
about carers' willingness and ability to provide support. We also report
perceived tensions between family carers and practitioners around appropriate
involvement in decision-making. The study findings have implications for local
authorities, practitioners and family carers in supporting the involvement of
family carers in support for people with severe mental health problems.
PMID- 26435492
TI - Endoscopic endonasal greater palatine artery cauterization at the incisive
foramen for control of anterior epistaxis.
AB - OBJECTIVES/HYPOTHESIS: To describe the anatomy of the incisive foramen and the
transnasal endoscopic approach to the greater palatine artery at this foramen,
and to evaluate the importance of the greater palatine artery as a cause of
recurrent anterior epistaxis. STUDY DESIGN: Anatomical dissection, radiographic
study, and prospective case series. SETTING: Academic Medical Center. METHODS:
Sixty-nine computed tomography scans were reviewed, and measurements were made of
the incisive foramina's distance to the anterior nasal spine and subnasale.
Twenty-two cadavers had sagittal split craniotomies performed prior to the
measurements. The distance from the anterior nasal spine to the incisive foramen
was documented. We also present an illustrative case series of patients who
underwent endoscopic cautery of the greater palatine artery at the incisive
foramen. RESULTS: Radiographic review of the incisive foramen revealed a mean
anterior nasal spine to incisive foramen distance on the right and left of 7.9
and 8.1 mm, respectively. The mean distance from the subnasale to incisive
foramen on the right and left were 24.7 and 24.9 mm, respectively. CONCLUSIONS:
Endoscopic cauterization of the greater palatine artery at the incisive foramen
is a safe and effective method to control recurrent anterior epistaxis. The
incisive foramen can be predictively found within 1 cm of the anterior nasal
spine. Our case series corroborates the above. LEVEL OF EVIDENCE: 4.
Laryngoscope, 126:1033-1038, 2016.
PMID- 26435493
TI - Reproducibility of cerebrovascular reactivity measures in children using BOLD
MRI.
AB - PURPOSE: To evaluate the reproducibility of cerebrovascular reactivity (CVR)
measurements acquired in children using magnetic resonance imaging (MRI) in
combination with a computer-controlled carbon dioxide (CO2 ) stimulus. MATERIALS
AND METHODS: Ten healthy children (age 16.1 +/- 1.6 years) underwent CVR imaging
on a 3T scanner using a blood-oxygen level-dependent (BOLD) MRI sequence.
Targeted hypercapnia was induced during imaging with a CO2 gas challenge
delivered using a specialized gas sequencer (RespirAct). A total of four BOLD
scans were performed over 2 separate days to test within-day and between-day
consistency of the data. CVR values were computed by correlating the relative
change in BOLD signal in response to the CO2 stimulus delivered to the each
subject. RESULTS: Intraclass correlation coefficients (ICCs) of within-day values
show highly reproducible measures in both the gray matter (ICC = 0.857, P <
0.001) and white matter (ICC = 0.895, P < 0.001). Relatively lower between-day
reproducibility was observed in both the gray matter (ICC = 0.776, P = 0.001) and
white matter (ICC = 0.719, P = 0.004). CONCLUSION: Using a computer-controlled
CO2 stimulus, we have demonstrated the reliability of BOLD-CVR measurements in
pediatric subjects. Within-day and between-day metrics of reproducibility were
comparable to adult data.
PMID- 26435494
TI - Uterine balloon tamponade: the case against technology.
PMID- 26435496
TI - First-Trimester Pregnancy Exposure to Venlafaxine or Duloxetine and Risk of Major
Congenital Malformations: A Systematic Review.
AB - Major depressive disorder is common among women in child-bearing age, and medical
treatment is subject to substantial discussions and controversies. For Selective
Serotonin reuptake inhibitors, SSRIs, a vast amount of data are available. For
the newer antidepressant group of serotonin and noradrenaline reuptake
inhibitors, SNRIs, significantly less data are available. Following the PRISMA
guideline for systematic reviews, we performed a systematic search on the risk of
major congenital malformations after first trimester in utero exposure to
venlafaxine or duloxetine. We identified eight cohort studies reporting on the
outcome upon in utero exposure to venlafaxine or duloxetine during the first
trimester. The cumulated data for venlafaxine were 3186 exposed infants and 107
major malformations, resulting in a relative risk estimate and 95% confidence
interval of 1.12 (0.92-1.35). The corresponding data for duloxetine were 668
infants and 16 major malformations, resulting in a relative risk estimate and 95%
confidence interval of 0.80 (0.46-1.29). First-trimester in utero exposure to
venlafaxine is not associated with an increased risk of major congenital
malformations. The amount of data for duloxetine are significantly smaller but
does not suggest a clinically important increased risk.
PMID- 26435495
TI - Fatigue in chronic inflammation - a link to pain pathways.
AB - Fatigue is a frequent symptom in several inflammatory diseases, particularly in
rheumatic diseases. Elements of disease activity and cognitive and behavior
aspects have been reported as causes of fatigue in patients with rheumatoid
arthritis. Fatigue could be associated with activity of inflammatory rheumatism.
Indeed, biologic agents targeting inflammatory cytokines are effective in
fatigue. Fatigue is also associated with pain and depressive symptoms. Different
pathways could be involved in fatigue and interact: the immune system with
increased levels of pro-inflammatory cytokines (interleukin-1 and -6 and tumor
necrosis factor alpha), dysregulation of the hypothalamic-pituitary-adrenal axis
and neurological phenomena involving the central and autonomic nervous systems. A
pro-inflammatory process could be involved in pain and behavioral symptoms.
Inflammation could be a common link between fatigue, pain, and depression.
PMID- 26435497
TI - Differential expression profiles and roles of inducible DUSPs and ERK1/2-specific
constitutive DUSP6 and DUSP7 in microglia.
AB - Dual-specificity phosphatases (DUSPs) show distinct substrate preferences for
specific MAPKs. DUSPs sharing a substrate preference for ERK1/2 may be classified
as inducible or constitutive. In contrast to the inducible DUSPs which also
dephosphorylate p38 MAPK and JNK in the major inflammatory pathways, constitutive
DUSP6 and DUSP7 are specific to ERK1/2 and have not been studied in microglia and
other immune cells to date. In the present study, we differentiated mRNA
expression profiles of inducible and constitutive DUSPs that dephosphorylate
ERK1/2 in microglia. Lipopolysaccharide (LPS) at 1 ng/ml induced prompt
phosphorylation of ERK1/2 with peak induction at 30 min. LPS induced expression
of DUSP1, DUSP2, and DUSP5 within 60 min, whereas DUSP4 expression was induced
more slowly. DUSP6 and DUSP7 exhibited constitutive basal expression, which
decreased immediately after LPS stimulation but subsequently returned to basal
levels. The expression of DUSP6 and DUSP7 was regulated inverse to the
phosphorylation of ERK1/2 in LPS-stimulated microglia. Therefore, we next
investigated the correlation between DUSP6 and DUSP7 expression and ERK1/2
phosphorylation in resting and LPS-stimulated microglia. Inhibition of the ERK1/2
pathway by PD98059 and FR180204 resulted in a decrease in DUSP6 and DUSP7
expression, both in resting and LPS-stimulated microglia. These inhibitors
partially blocked the LPS-induced expression of DUSP1, DUSP2, and DUSP4, but had
no effect on DUSP5. Finally, we examined the role of DUSP6 activity in the
downregulation of ERK1/2 phosphorylation. BCI, an inhibitor of DUSP6, increased
the phosphorylation of ERK1/2. However, pretreatment with BCI inhibited the LPS
induced phosphorylation of ERK1/2. These results demonstrate that constitutive
DUPS6 and DUSP7 expression was downregulated inverse to the expression of
inducible DUSPs and the phosphorylation of ERK1/2 in LPS-stimulated microglia.
The expression of DUPS6 and DUSP7 was mediated by ERK1/2 activity both in resting
and LPS-stimulated microglia. In turn, DUSP6 suppressed the basal phosphorylation
of ERK1/2, but exerted no suppressive effect on LPS-induced phosphorylation.
Although DUSP6 is acknowledged as a negative regulator of the ERK1/2 pathway,
such roles of DUSP6 need to be examined further in activated microglia.
PMID- 26435498
TI - Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3.
AB - Mutations in with-no-lysine kinase (WNK) 1, WNK4, Kelch-like 3 (KLHL3), and
Cullin3 result in an inherited hypertensive disease, pseudohypoaldosteronism type
II. WNK activates the Na-Cl cotransporter (NCC), increasing sodium reabsorption
in the kidney. Further, KLHL3, an adapter protein of Cullin3-based E3 ubiquitin
ligase, has been recently found to bind to WNK, thereby degrading them. Insulin
and vasopressin have been identified as powerful activators of WNK signaling. In
this study, we investigated effects of Akt and PKA, key downstream substrates of
insulin and vasopressin signaling, respectively, on KLHL3. Mass spectrometry
analysis revealed that KLHL3 phosphorylation at S433. Phospho-specific antibody
demonstrated defective binding between phosphorylated KLHL3 and WNK4. Consistent
with the fact that S433 is a component of Akt and PKA phosphorylation motifs, in
vitro kinase assay demonstrated that Akt and PKA can phosphorylate KLHL3 at S433,
that was previously reported to be phosphorylated by PKC. Further, forskolin, a
representative PKA stimulator, increased phosphorylation of KLHL3 at S433 and
WNK4 protein expression in HEK293 cells by inhibiting the KLHL3 effect that leads
to WNK4 degradation. Insulin also increased phosphorylation of KLHL3 at S433 in
cultured cells. In conclusion, we found that Akt and PKA phosphorylated KLHL3 at
S433, and phosphorylation of KLHL3 by PKA inhibited WNK4 degradation. This could
be a novel mechanism on how insulin and vasopressin physiologically activate the
WNK signal.
PMID- 26435499
TI - Down-regulation of TCF21 by hypermethylation induces cell proliferation,
migration and invasion in colorectal cancer.
AB - Epigenetic alteration induced loss function of the transcription factor 21
(TCF21) has been associated with different types of human cancers. However, the
epigenetic regulation and molecular functions of TCF21 in colorectal cancer (CRC)
remain unknown. In this study, TCF21 expression levels and methylation status of
its promoter region in CRC cell lines (n = 5) and CRC tissues (n = 151) as well
as normal colorectal mucosa (n = 30) were assessed by RTq-PCR and methylation
analysis (methylation specific PCR, MSP and bisulfite sequencing PCR, BSP),
respectively. The cellular functions of TCF21 on CRC cell proliferation,
apoptosis, invasion and migration were investigated in vitro. Our data revealed
that TCF21 was frequently silenced by promoter hypermethylation in both tested
CRC cell lines and primary CRC, and correlation analysis between methylation
status and clinicopathologic parameters found that TCF21 methylation was
significantly correlated with lymph node invasion (P = 0.013), while no
significant correlation was found in other parameters. In addition, demethylation
treatment resulted in re-expression of TCF21 in CRC cell lines, and cellular
function experiments revealed that restoration of TCF21 inhibited CRC cell
proliferation, promoted apoptosis and suppressed cell invasion and migration,
suggesting that TCF21 may function as a tumor suppressor gene, which is
downregulated through promoter hypermethylation in CRC development.
PMID- 26435500
TI - Ubiquitination-dependent degradation of p73 by the mitochondrial E3 ubiquitin
ligase Hades.
AB - p73 is a member of the p53 family of transcription factors which plays an
essential role in tumor suppression. p73 is associated with the sensitivity of
cancer cells to chemotherapy and the prognosis of many cancers. In this study, we
showed the ubiquitination-dependent degradation of p73 by the mitochondrial E3
ubiquitin ligase Hades. First, the binding between p73 and Hades was identified
by co-immunoprecipitation experiments, and it was found that the Hades RING
finger domain mediates the interaction with p73. Immunofluorescence analysis
showed that p73 moves to the mitochondria and colocalizes with Hades during
etoposide-induced apoptosis. By performing in vivo and in vitro ubiquitination
assays, we observed that the Hades RING-finger domain promotes ubiquitination of
p73. Finally, it was shown that SiRNA-mediated depletion of Hades stabilizes p73.
Taken together, our results showed that Hades mediates the ubiquitination
dependent degradation of mitochondrial p73 under apoptotic conditions. These
findings suggest that Hades-mediated p73 ubiquitination is a novel regulatory
mechanism for the exonuclear function of p73.
PMID- 26435501
TI - Angiopoietin-like protein 2 induces proinflammatory responses in peritoneal
cells.
AB - Monocytes and macrophages are important effectors and regulators of inflammation,
and both their differentiation and activation are regulated strictly in response
to environmental cues. Angiopoietin-like protein 2 (Angptl2) is a multifaceted
protein, displaying many physiological and pathological functions in
inflammation, angiogenesis, hematopoiesis, and tumor development. Although recent
studies implicate Angptl2 in chronic inflammation, the mechanisms of inflammation
caused by Angptl2 remain unclear. The purpose of the present study was to
elucidate the role of Angptl2 in inflammation by understanding the effects of
Angptl2 on monocytes/macrophages. We showed that Angptl2 directly activates
resident murine peritoneal monocytes and macrophages and induces a drastic
upregulation of the transcription of several inflammatory genes including nitric
oxide synthase 2 and prostaglandin-endoperoxide synthase 2, and several
proinflammatory cytokine genes such as interleukin (IL)-1beta, IL-6, TNFalpha,
and CSF2, along with activation of ERK, JNK, p38, and nuclear factor kappa B
signaling pathways. Concordantly, proinflammatory cytokines IL-1beta, IL-6,
TNFalpha, and GM-CSF, were rapidly elevated from murine peritoneal monocytes and
macrophages. These results demonstrate a novel role for Angptl2 in inflammation
via the direct activation of peritoneal monocytes and macrophages.
PMID- 26435502
TI - Podocyte-specific deletion of Rac1 leads to aggravation of renal injury in STZ
induced diabetic mice.
AB - Rac1, a GTPase of the Rho subfamily, has a crucial role in cytoskeletal
architecture, as well as the regulation of cell migration and growth. However,
renal injury in mice with podocyte-specific deletion of Rac1 has yet to be
elucidated fully due to conflicting findings. Herein, we identified a possible
role for Rac1 in podocytes of streptozotocin- (STZ) induced diabetic mice. The
urinary albumin/creatinine ratio (ACR) in the knockout (KO) group was
significantly higher than that in the wild type (WT) group at any week of age. A
more marked ACR increase was observed in STZ/KO group than STZ/WT group, although
ACR did increase with weeks of age in both diabetic groups. The kidney sections
from diabetic mice revealed a glomerular hypertrophy with mesangial expansion,
but there was no appreciable difference in glomerular findings under a light
microscope between STZ/WT and STZ/KO mice. However, an electron microscopy
analysis revealed that regardless of the presence or absence of diabetes, both KO
(KO and STZ/KO) groups had a higher rate of foot process effacement compared with
both WT (WT and STZ/WT) groups. The expression levels of the slit diaphragm
protein, podocin, was reduced with the induction of diabetes, and the levels in
the STZ/KO group experienced a further reduction compared with the STZ/WT group.
The number of WT1-positive cells in the STZ/KO group was more significantly
decreased than that in the other three groups. In contrast, the numbers of
cleaved caspase 3- and TUNEL-positive cells in the glomeruli of the STZ/KO group
were more increased than those in the STZ/WT group. Thus, this study provides
evidence that podocyte-specific deletion of Rac1 results in morphological
alteration in podocytes, and that the induction of apoptosis or decreased
expression of the slit diaphragm proteins by hyperglycemic stimuli are associated
with the progression of diabetic nephropathy.
PMID- 26435503
TI - NFkappaB-p50 as a blood based protein marker for early diagnosis and prognosis of
head and neck squamous cell carcinoma.
AB - Head and neck squamous cell carcinoma (HNSCC) is the major health concern in
Indian population. Despite of advanced treatment the mortality rate for this
disease has not been improved very much. Current research focused on development
of protein marker for the diagnosis and prognosis of HNSCC. The case control
study was performed with 125 HNSCC patients and 104 control cases. The level of
p50 and IkappaBalpha proteins in serum were evaluated at pre and post therapy by
label free real time surface plasmon resonance (SPR) and western blot analysis.
The serum p50 concentration were significantly (P < 0.0001) higher at the time of
diagnosis i.e. pre therapy (Mean +/- SD = 27.06 +/- 4.88 ng/MUl) as compared to
controls (Mean +/- SD = 16.96 +/- 4.04 ng/MUl) while it decline at post therapy
(Mean +/- SD = 21.01 +/- 4.98 ng/MUl). Similarly, the concentration of
IkappaBalpha protein in serum were slightly higher at pre therapy (Mean +/- SD =
8.33 +/- 1.85 ng/MUl) as compared to controls (Mean +/- SD = 7.27 +/- 1.84
ng/MUl) and declined at post therapy (Mean +/- SD = 7.09 +/- 1.24 ng/MUl). The
level of p50 was also high at the early stage of the disease. The specificity and
sensitivity of p50 proteins obtained from ROC analysis revealed the potentiality
to be diagnostic protein marker for HNSCC for its accuracy in the study cohort.
PMID- 26435504
TI - T gene isoform expression pattern is significantly different between chordomas
and notochords.
AB - The T gene plays a key role in chordoma pathology. To investigate the role of T
gene isoforms in chordoma, 22 skull base chordomas, three chordoma cell lines and
9 infant notochords, which were used as normal controls, were collected. We first
conducted droplet digital PCR to quantify the absolute expression levels of the
long and short isoforms of the T gene (T-long and T-short, respectively) and
revealed that T-long was dominantly expressed in all chordomas and chordoma cell
lines, but not in the notochords. The T-long/T-short ratio was significantly
different between the chordomas and the notochords. Next, we validated the
isoform expression pattern at protein expression level using Western blot in 9
chordomas. Furthermore, the T gene single nucleotide polymorphism site rs2305089,
which is the only marker reported to be associated with chordomas, was sequenced
in all of the chordoma samples. Association between rs2305089 and T-long/T-short
ratio was not significant, indicating it was not involved in T gene alternative
splicing. In conclusion, two T gene isoforms were investigated in skull base
chordomas and chordoma cell lines, and the longer isoform was dominantly
expressed. The distinct expression patterns of these T gene isoforms may
contribute to the pathogenesis of skull base chordomas. However, further studies
on the function of these isoforms are needed.
PMID- 26435506
TI - Analysis of the electrostatics in Dy(III) single-molecule magnets: the case study
of Dy(Murex)3.
AB - A Dy(III)-based single-molecule magnet is reported. Ab initio calculations
highlight that molecular symmetry plays a predominant role over site symmetry in
determining the shape and orientation of Dy(III) magnetic anisotropy. Moreover
the dipolar component of the electrostatic potential created by the surrounding
ligands is shown to be the driving force of its magnetic behaviour.
PMID- 26435505
TI - Inhibition of LSD1 by Pargyline inhibited process of EMT and delayed progression
of prostate cancer in vivo.
AB - Recently, lysine-specific demethylase 1 (LSD1) was identified as the first
histone demethylase. LSD1 interacted with androgen receptor (AR) and promoted
androgen-dependent transcription of target genes, such as PSA, by ligand-induced
demethylation of mono- and dimethylated histone H3 at Lys 9 (H3K9). Meanwhile,
the phenomenon of epithelial-mesenchymal transition (EMT) had received
considerable attention in tumor recurrence and metastasis. This study examined
the effect of Pargyline (an inhibitor of LSD1) on the process of EMT in vitro and
in vivo. SCID mice were injected subcutaneously with LNCap cells. Pargyline was
given intraperitoneally or not after castration (implemented with Bilateral
orchidectomy), then PSA levels in serum and tumor were determined to assess time
to androgen-independent progression. The results showed that LSD1 expression was
up-regulated when PCa progressed to Castration Resistant Prostate Cancer (CRPC).
Pargyline reduced LNCap cells migration and invasion ability, and inhibited the
process of EMT by up-regulating expression of E-cadherin, and down-regulating
expressions of N-cadherin and Vimentin in vitro and in vivo. Although, Pargyline
did not change the level of AR, it reduced PSA expression both in vitro and in
vivo. Furthermore, Pargyline delayed prostate cancer transition from androgen
dependent to androgen-independent state (CRPC). These findings indicated that
inhibition of LSD1 might be a promise adjunctive therapy with androgen
deprivation therapy (ADT) for locally advanced or metastatic prostate cancer.
PMID- 26435507
TI - Characterizing Cardiac Molecular Mechanisms of Mammalian Hibernation via
Quantitative Proteogenomics.
AB - This study uses advanced proteogenomic approaches in a nonmodel organism to
elucidate cardioprotective mechanisms used during mammalian hibernation.
Mammalian hibernation is characterized by drastic reductions in body temperature,
heart rate, metabolism, and oxygen consumption. These changes pose significant
challenges to the physiology of hibernators, especially for the heart, which
maintains function throughout the extreme conditions, resembling ischemia and
reperfusion. To identify novel cardioadaptive strategies, we merged large-scale
RNA-seq data with large-scale iTRAQ-based proteomic data in heart tissue from 13
lined ground squirrels (Ictidomys tridecemlineatus) throughout the circannual
cycle. Protein identification and data analysis were run through Galaxy-P, a new
multiomic data analysis platform enabling effective integration of RNA-seq and
MS/MS proteomic data. Galaxy-P uses flexible, modular workflows that combine
customized sequence database searching and iTRAQ quantification to identify novel
ground squirrel-specific protein sequences and provide insight into molecular
mechanisms of hibernation. This study allowed for the quantification of 2007
identified cardiac proteins, including over 350 peptide sequences derived from
previously uncharacterized protein products. Identification of these peptides
allows for improved genomic annotation of this nonmodel organism, as well as
identification of potential splice variants, mutations, and genome
reorganizations that provides insights into novel cardioprotective mechanisms
used during hibernation.
PMID- 26435508
TI - The role of gluconate production by Pseudomonas spp. in the mineralization and
bioavailability of calcium-phytate to Nicotiana tabacum.
AB - Organic phosphorus (P) is abundant in most soils but is largely unavailable to
plants. Pseudomonas spp. can improve the availability of P to plants through the
production of phytases and organic anions. Gluconate is a major component of
Pseudomonas organic anion production and may therefore play an important role in
the mineralization of insoluble organic P forms such as calcium-phytate (CaIHP).
Organic anion and phytase production was characterized in 2 Pseudomonas spp. soil
isolates (CCAR59, Ha200) and an isogenic mutant of strain Ha200, which lacked a
functional glucose dehydrogenase (Gcd) gene (strain Ha200 gcd::Tn5B8). Wild-type
and mutant strains of Pseudomonas spp. were evaluated for their ability to
solubilize and hydrolyze CaIHP and to promote the growth and assimilation of P by
tobacco plants. Gluconate, 2-keto-gluconate, pyruvate, ascorbate, acetate, and
formate were detected in Pseudomonas spp. supernatants. Wild-type pseudomonads
containing a functional gcd could produce gluconate and mineralize CaIHP, whereas
the isogenic mutant could not. Inoculation with Pseudomonas improved the
bioavailability of CaIHP to tobacco plants, but there was no difference in plant
growth response due to Gcd function. Gcd function is required for the
mineralization of CaIHP in vitro; however, further studies will be needed to
quantify the relative contribution of specific organic anions such as gluconate
to plant growth promotion by soil pseudomonads.
PMID- 26435512
TI - Mutational mapping of the transmembrane binding site of the G-protein coupled
receptor TGR5 and binding mode prediction of TGR5 agonists.
AB - TGR5 (Gpbar-1, M-Bar) is a class A G-protein coupled bile acid-sensing receptor
predominately expressed in brain, liver and gastrointestinal tract, and a
promising drug target for the treatment of metabolic disorders. Due to the lack
of a crystal structure of TGR5, the development of TGR5 agonists has been guided
by ligand-based approaches so far. Three binding mode models of bile acid
derivatives have been presented recently. However, they differ from one another
in terms of overall orientation or with respect to the location and interactions
of the cholane scaffold, or cannot explain all results from mutagenesis
experiments. Here, we present an extended binding mode model based on an
iterative and integrated computational and biological approach. An alignment of
68 TGR5 agonists based on this binding mode leads to a significant and good
structure-based 3D QSAR model, which constitutes the most comprehensive structure
based 3D-QSAR study of TGR5 agonists undertaken so far and suggests that the
binding mode model is a close representation of the "true" binding mode. The
binding mode model is further substantiated in that effects predicted for eight
mutations in the binding site agree with experimental analyses on the impact of
these TGR5 variants on receptor activity. In the binding mode, the hydrophobic
cholane scaffold of taurolithocholate orients towards the interior of the
orthosteric binding site such that rings A and B are in contact with TM5 and TM6,
the taurine side chain orients towards the extracellular opening of the binding
site and forms a salt bridge with R79(EL1), and the 3-hydroxyl group forms
hydrogen bonds with E169(5.44) and Y240(6.51). The binding mode thus differs in
important aspects from the ones recently presented. These results are highly
relevant for the development of novel, more potent agonists of TGR5 and should be
a valuable starting point for the development of TGR5 antagonists, which could
show antiproliferative effects in tumor cells.
PMID- 26435513
TI - Synthesis, antimycobacterial and antibacterial activity of fluoroquinolone
derivatives containing an 3-alkoxyimino-4-(cyclopropylanimo)methylpyrrolidine
moiety.
AB - A series of novel fluoroquinolone derivatives containing an 3-alkoxyimino-4
(cyclopropylanimo)methylpyrrolidine moiety were designed, synthesized and
evaluated for their biological activity. Our results revealed that 19b2 shows
good activity against MTB H37Rv ATCC 27294 (MIC: <0.25 MUg/mL) and MDR-MTB 6133
clinical isolate (MIC: 0.11 MUg/mL). Most of them have potent potency against
Gram-positive strains, although they are generally poor active against Gram
negative strains. Especially, compounds 22b1 and 23a3 (MICs: <0.008-8 MUg/mL)
were found to 2-128 times more potent than ciprofloxacin and levofloxacin against
all of the tested Gram-positive strains including quinolone-resistant MRSA, MRSE,
Enterococcus faecium and Enterococcus faecalis.
PMID- 26435515
TI - Rational design of YAP WW1 domain-binding peptides to target TGFbeta/BMP/Smad-YAP
interaction in heterotopic ossification.
AB - The transforming growth factor-beta/bone morphogenic protein/Smad signaling
pathway has been raised as a new and promising therapeutic target of heterotopic
ossification, which is mediated by recruitment of transcription coactivator Yes
associated protein (YAP) to Smad. Here, we described a successful integration of
computational modeling and experimental assay to rationally design novel peptide
aptamers to disrupt YAP-Smad interaction by targeting YAP WW1 domain. In the
protocol, a computational genetic evolution strategy was used to improve a
population of potential YAP WW1-binding peptides generated from the YAP
recognition site in Smad protein, from which several promising peptides were
selected and their affinities toward YAP WW1 domain were determined using binding
assay. In addition, a high-activity peptide was further optimized based on its
complex structure with YAP WW1 domain to derive a number of derivative peptides
with higher binding potency to the domain. We also found that a strong YAP WW1
binder should have a negatively charged N-terminus, a positively charged C
terminus and a nonpolar core to match the electrostatic distribution pattern in
peptide-binding pocket of YAP WW1 domain, which may also form additional
nonbonded interactions such as hydrogen bond, salt bridge and pi-pi stacking to
confer stability and specificity for the domain-peptide recognition.
PMID- 26435514
TI - Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification
of beta-amyloid plaques by positron emission tomography.
AB - A new series of fluoro-pegylated benzyloxybenzenes were designed, synthesized and
evaluated as PET probes for early detection of Abeta plaques. Molecular docking
revealed that all of the flexible benzyloxybenzenes inserted themselves into the
hydrophobic Val18_Phe20 cleft on the flat spine of the Abeta fiber, in a manner
similar to that of IMPY molecule. The most potent probe, [(18)F]9a, exhibited a
combination of high binding affinity to Abeta aggregates (Ki = 21.0 +/- 4.9 nM),
high initial brain uptake (9.14% ID/g at 2 min), fast clearance from normal brain
tissue (1.79% ID/g at 60 min), and satisfactory in vivo biostability in the brain
(95% of intact form at 2 min). [(18)F]9a clearly labeled Abeta plaques in in
vitro autoradiography of postmortem AD patients and Tg mice brain sections. Ex
vivo autoradiography further demonstrated that [(18)F]9a did penetrate the intact
BBB and specifically bind to Abeta plaques in vivo. Overall, [(18)F]9a may be a
potential PET probe for imaging Abeta plaques in AD brains.
PMID- 26435516
TI - A new potential energy surface for the H2S system and dynamics study on the
S((1)D) + H2(X(1)Sigmag(+)) reaction.
AB - We constructed a new global potential energy surface (PES) for the electronic
ground state ((1)A') of H2S based on 21,300 accurate ab initio energy points over
a large configuration space. The ab initio energies are obtained from
multireference configuration interaction calculations with a Davidson correction
using basis sets of quadruple zeta quality. The neural network method is applied
to fit the PES, and the root mean square error of fitting is small (1.68 meV).
Time-dependent wave packet studies for the S((1)D) + H2(X(1)Sigmag(+)) -> H((2)S)
+ SH(X(2)Pi) reaction on the new PES are conducted to study the reaction
dynamics. The calculated integral cross sections decrease with increasing
collision energy and remain fairly constant within the high collision energy
range. Both forward and backward scatterings can be observed as expected for a
barrierless reaction with a deep well on the PES. The calculated integral cross
sections and differential cross sections are in good agreement with the
experimental results.
PMID- 26435517
TI - Translocation from nuclei to cytoplasm is necessary for anti A-PCD activity and
turnover of the Type II IAP BcBir1.
AB - Type II inhibitors of apoptosis (IAPs) belong to a subgroup of IAP-related
proteins. While IAPs are restricted to animals, Type II IAPs are found in other
phyla, including fungi. BcBir1, a Type II IAP from Botrytis cinerea has anti
apoptotic-like programmed cell death (A-PCD) activity, which is important for
pathogenicity of this fungus. Here we report on the role of sub-cellular
localization of BcBir1 in protein turnover and anti A-PCD activity. Expression of
BcBir1 in Saccharomyces cerevisiae had no effect on sensitivity of the yeast
cells to A-PCD-inducing conditions, whereas expression of a truncated N' part
reduced sensitivity of the cells to these conditions. The full-length BcBir1
protein was detected only in the yeast nucleus, whereas the N' part was observed
both in the nucleus and cytoplasm. In B. cinerea, BcBir1 was mainly nuclear under
optimal conditions, whereas under A-PCD-inducing conditions it shuttled to the
cytoplasm and then it was completely degraded. Collectively, our results show
that anti A-PCD activity of BcBir1 occurs in the cytoplasm, the C' end mediates
regulation of steady state level of BcBir1 in the nucleus, and the N' end
mediates anti A-PCD activity as well as fast degradation of BcBir1 in the
cytoplasm.
PMID- 26435518
TI - Multilayer hexagonal silicon forming in slit nanopore.
AB - The solidification of two-dimensional liquid silicon confined to a slit nanopore
has been studied using molecular dynamics simulations. The results clearly show
that the system undergoes an obvious transition from liquid to multilayer
hexagonal film with the decrease of temperature, accompanied by dramatic change
in potential energy, atomic volume, coordination number and lateral radial
distribution function. During the cooling process, some hexagonal islands
randomly appear in the liquid first, then grow up to grain nuclei, and finally
connect together to form a complete polycrystalline film. Moreover, it is found
that the quenching rate and slit size are of vital importance to the freezing
structure of silicon film. The results also indicate that the slit nanopore
induces the layering of liquid silicon, which further induces the slit size
dependent solidification behavior of silicon film with different electrical
properties.
PMID- 26435519
TI - Increasing prevalence of ciprofloxacin-resistant food-borne Salmonella strains
harboring multiple PMQR elements but not target gene mutations.
AB - Fluoroquinolone resistance in Salmonella has become increasingly prevalent in
recent years. To probe the molecular basis of this phenomenon, the genetic and
phenotypic features of fluoroquinolone resistant Salmonella strains isolated from
food samples were characterized. Among the 82 Salmonella strains tested,
resistance rate of the three front line antibiotics of ceftriaxone, ciprofloxacin
and azithromycin was 10%, 39% and 25% respectively, which is significantly higher
than that reported in other countries. Ciprofloxacin resistant strains typically
exhibited cross-resistance to multiple antibiotics including ceftriaxone,
primarily due to the presence of multiple PMQR genes and the blaCTX-M-65, blaCTX
M-55 blaCMY-2 and blaCMY-72 elements. The prevalence rate of the oqxAB and
aac(6')-Ib-cr genes were 91% and 75% respectively, followed by qnrS (66%), qnrB
(16%) and qnrD (3%). The most common PMQR combination observable was aac(6')-Ib
cr-oqxAB-qnrS2, which accounted for 50% of the ciprofloxacin resistant strains.
Interestingly, such isolates contained either no target mutations or only a
single gyrA mutation. Conjugation and hybridization experiments suggested that
most PMQR genes were located either in the chromosome or a non-transferrable
plasmid. To summarize, findings in this work suggested that PMQRs greatly
facilitate development of fluoroquinolone resistance in Salmonella by abolishing
the requirement of target gene mutations.
PMID- 26435520
TI - Meckel diverticulum in children: Evaluation of macroscopic appearance for
guidance in subsequent surgery.
AB - BACKGROUND: The treatment of incidentally encountered asymptomatic Meckel
diverticulum (MD) is controversial. We evaluated whether the macroscopic
appearance correlates with clinical features, histopathological findings, future
complications, and management decisions. METHODS: Patients who underwent MD
resection at a single institution from 2000 to 2012 were retrospectively analyzed
in terms of age, sex, clinical features, laboratory data, perioperative findings
(diverticulum length, diameter, depth, thickening, and height-to diameter ratio
[HDR]), pathology, and postoperative follow-up. RESULTS: Fifty children were
enrolled. Sixteen percent of the resected MDs were found incidentally. Of 42
complicated MDs, 17 (40%) were long (HDR >=2), 14 (33%) were thickened, and 29
(70%) exhibited base widening. Histopathologically, ectopic mucosa was found in
32 (64%) of all MDs and in 5 (62%) of incidentally removed MDs. There was no
statistical difference between the macroscopic appearance and clinical signs,
sex, or presence of ectopic tissue based on palpation. CONCLUSION: The
macroscopic appearance of MD does not indicate the presence or absence of HGM and
cannot be used to guide subsequent surgery. Additionally, 40% of symptomatic
patients in our study had life-threatening complications requiring prompt fluid
resuscitation. We consider that incidentally detected MD should be removed
regardless of its macroscopic appearance.
PMID- 26435521
TI - Enteral refeeding is useful for promoting growth in neonates with enterostomy
before stoma closure.
AB - BACKGROUND: Enterostomy may lead to fluid and electrolyte imbalance, or impaired
absorption of nutrition followed by impairment of growth. This study aimed to
clarify the effectiveness of enteral refeeding (ER) in premature and full-term
neonates. METHODS: A retrospective database of all consecutive neonates who had
enterostomy during 2000-2014 in a regional center was analyzed. Thirteen patients
with ER (ER group) and 14 patients without ER (control group) were included.
Detailed clinical data were evaluated with reference to the increment in body
weight during ER. RESULTS: The ER group had a significantly higher rate in weight
gain compared with the control group (P=0.0012), despite the gestational age
(<37weeks: P=0.0012, >=37weeks: P=0.029). ER starting at a lower body weight was
also associated with a higher weight gain (P=0.0002). Moreover, univariate and
multivariate analyses showed that only the ER procedure (P<0.0001) and birth
weight (P=0.049) were significantly independent predictors of good weight gain.
CONCLUSIONS: Using ER, low-birth-weight infants may have benefits, such as better
acceleration of growth, than normal-birth-weight infants. We do not hesitate to
perform ER, even in low-birth-weight neonates or those with low body weight, when
starting ER.
PMID- 26435522
TI - Back to the future: Does in-hospital delay to appendectomy for pediatric
uncomplicated appendicitis increase risk for perforation?
PMID- 26435525
TI - A new tool for long-term studies of POM-bacteria interactions: overcoming the
century-old Bottle Effect.
AB - Downward fluxes of particulate organic matter (POM) are the major process for
sequestering atmospheric CO2 into aquatic sediments for thousands of years.
Budget calculations of the biological carbon pump are heavily based on the ratio
between carbon export (sedimentation) and remineralization (release to the
atmosphere). Current methodologies determine microbial dynamics on POM using
closed vessels, which are strongly biased towards heterotrophy due to rapidly
changing water chemistry (Bottle Effect). We developed a flow-through rolling
tank for long term studies that continuously maintains POM at near in-situ
conditions. There, bacterial communities resembled in-situ communities and
greatly differed from those in the closed systems. The active particle-associated
community in the flow-through system was stable for days, contrary to hours
previously reported for closed incubations. In contrast to enhanced respiration
rates, the decrease in photosynthetic rates on particles throughout the
incubation was much slower in our system than in traditional ones. These results
call for reevaluating experimentally-derived carbon fluxes estimated using
traditional methods.
PMID- 26435523
TI - Endometrial gene expression profile of pregnant sows with extreme phenotypes for
reproductive efficiency.
AB - Prolificacy can directly impact porcine profitability, but large genetic
variation and low heritability have been found regarding litter size among
porcine breeds. To identify key differences in gene expression associated to
swine reproductive efficiency, we performed a transcriptome analysis of sows'
endometrium from an Iberian x Meishan F2 population at day 30-32 of gestation,
classified according to their estimated breeding value (EBV) as high (H, EBV > 0)
and low (L, EBV < 0) prolificacy phenotypes. For each sample, mRNA and small RNA
libraries were RNA-sequenced, identifying 141 genes and 10 miRNAs differentially
expressed between H and L groups. We selected four miRNAs based on their role in
reproduction, and five genes displaying the highest differences and a positive
mapping into known reproductive QTLs for RT-qPCR validation on the whole extreme
population. Significant differences were validated for genes: PTGS2 (p = 0.03;
H/L ratio = 3.50), PTHLH (p = 0.03; H/L ratio = 3.69), MMP8 (p = 0.01; H/L ratio
=4.41) and SCNN1G (p = 0.04; H/L ratio = 3.42). Although selected miRNAs showed
similar expression levels between H and L groups, significant correlation was
found between the expression level of ssc-miR-133a (p < 0.01) and ssc-miR-92a (p
< 0.01) and validated genes. These results provide a better understanding of the
genetic architecture of prolificacy-related traits and embryo implantation
failure in pigs.
PMID- 26435527
TI - Hit and lead criteria in drug discovery for infectious diseases of the developing
world.
AB - Reducing the burden of infectious diseases that affect people in the developing
world requires sustained collaborative drug discovery efforts. The quality of the
chemical starting points for such projects is a key factor in improving the
likelihood of clinical success, and so it is important to set clear go/no-go
criteria for the progression of hit and lead compounds. With this in mind, the
Japanese Global Health Innovative Technology (GHIT) Fund convened with experts
from the Medicines for Malaria Venture, the Drugs for Neglected Diseases
initiative and the TB Alliance, together with representatives from the Bill
&Melinda Gates Foundation, to set disease-specific criteria for hits and leads
for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we
present the agreed criteria and discuss the underlying rationale.
PMID- 26435524
TI - Neural substrates of cue reactivity: association with treatment outcomes and
relapse.
AB - Given the strong evidence for neurological alterations at the basis of drug
dependence, functional magnetic resonance imaging (fMRI) represents an important
tool in the clinical neuroscience of addiction. fMRI cue-reactivity paradigms
represent an ideal platform to probe the involvement of neurobiological pathways
subserving the reward/motivation system in addiction and potentially offer a
translational mechanism by which interventions and behavioral predictions can be
tested. Thus, this review summarizes the research that has applied fMRI cue
reactivity paradigms to the study of adult substance use disorder treatment
responses. Studies utilizing fMRI cue-reactivity paradigms for the prediction of
relapse and as a means to investigate psychosocial and pharmacological treatment
effects on cue-elicited brain activation are presented within four primary
categories of substances: alcohol, nicotine, cocaine and opioids. Lastly,
suggestions for how to leverage fMRI technology to advance addiction science and
treatment development are provided.
PMID- 26435528
TI - Regulatory watch: Characterizing the US FDA's approach to promoting
transformative innovation.
PMID- 26435529
TI - Imaging normal and cancerous human gastric muscular layer in transverse and
longitudinal sections by multiphoton microscopy.
AB - Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and
second harmonic generation (SHG) has been widely used for imaging microstructure
of biological tissues. In this article, we used MPM to investigate the
microstructure changes of normal and cancerous human gastric muscular layer in
transverse and longitudinal sections. The results displayed different patterns of
microstructure changes of smooth muscular tissue, cell morphology and
interstitial fibers in transverse and longitudinal sections, being similar to
standard histopathological images but without the need for tissue processing. Our
study demonstrated that MPM can bring more detailed complementary information on
tissue architecture through observing transverse and longitudinal sections of
tissues, which are the important pathological information when the pathologists
diagnose the gastrointestinal lesions. These observations indicate that MPM could
be an important potential tool to provide real-time pathological diagnosis for
gastric cancer in the future. SCANNING 38:357-364, 2016. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26435531
TI - Cathinones: Isotopic profiling as an aid to linking seizures.
AB - The number of cathinone derivatives available to the street market has increased
steadily since 2008. Many of these compounds have proven to be potent
psychostimulants and fatalities have occurred through their recreational use. The
method of manufacture is essentially the same for each cathinone, i.e., (i)
selection of the appropriate beta-ketoarylalkane, (ii) bromination alpha to the
keto group, followed by (iii) amination using the desired amine. The cathinone
derivatives are usually prepared at a very high purity and little information is
available from an organic manufacturing by-products profile because the product
is so pure. To provide law enforcement agencies with a tool that would enable
links to be identified between samples from the same production batch, the
carbon, hydrogen, and nitrogen stable isotope ratios in a number of cathinones
were investigated. The aim was to determine if sufficient diversity existed in
the light element stable isotope ratios of cathinones to allow the isotopic
ratios to be used to discriminate between different seizures and to assist in
linking samples from the same seizure. Careful measurement of the delta(13) C,
delta(15) N, and delta(2) H values in each sample revealed that the stable
isotope ratios for a particular cathinone analogue vary from one seizure to
another. In the seizures studied, carbon, hydrogen, and nitrogen stable isotope
ratios were found to vary from -32.80/00 to -26.10/00, -1520/00 to +720/00, and
16.60/00 to -2.70/00, respectively. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26435532
TI - Temperature effects on polygraph detection of concealed information.
AB - Thermoregulatory influences on electrodermal and cardiovascular activity may
interfere with the detection of concealed information using a polygraph. This
possibility was assessed by means of a mock terrorism scenario. Seventy-two
participants were assigned to either a guilty or an innocent role. They were
given a polygraph test at one of three ambient temperatures: 10 degrees C, 22
degrees C, or 34 degrees C. Among guilty participants, electrodermal and
cardiovascular measures were least effective at 10 degrees C. Electrodermal
results were optimal at 22 degrees C, whereas cardiovascular results were optimal
at 34 degrees C. Among innocent participants, the effectiveness of these same
measures was not affected by ambient temperature. Temperature had no significant
impact on respiration results within the guilty or the innocent groups. Taken
together, these findings have implications for those who use polygraphs in
uncontrolled testing environments.
PMID- 26435530
TI - Mutations in circularly permuted GTPase family genes AtNOA1/RIF1/SVR10 and BPG2
suppress var2-mediated leaf variegation in Arabidopsis thaliana.
AB - Leaf variegation mutants constitute a unique group of chloroplast development
mutants and are ideal genetic materials to dissect the regulation of chloroplast
development. We have utilized the Arabidopsis yellow variegated (var2) mutant and
genetic suppressor analysis to probe the mechanisms of chloroplast development.
Here we report the isolation of a new var2 suppressor locus SUPPRESSOR OF
VARIEGATION (SVR10). Genetic mapping and molecular complementation indicated that
SVR10 encodes a circularly permuted GTPase that has been reported as Arabidopsis
thaliana NITRIC OXIDE ASSOCIATED 1 (AtNOA1) and RESISTANT TO INHIBITION BY
FOSMIDOMYCIN 1 (RIF1). Biochemical evidence showed that SVR10/AtNOA1/RIF1 likely
localizes to the chloroplast stroma. We further demonstrate that the mutant of a
close homologue of SVR10/AtNOA1/RIF1, BRASSINAZOLE INSENSITIVE PALE GREEN 2
(BPG2), can also suppress var2 leaf variegation. Mutants of SVR10 and BPG2 are
impaired in photosynthesis and the accumulation of chloroplast proteins.
Interestingly, two-dimensional blue native gel analysis showed that mutants of
SVR10 and BPG2 display defects in the assembly of thylakoid membrane complexes
including reduced levels of major photosynthetic complexes and the abnormal
accumulation of a chlorophyll-protein supercomplex containing photosystem I.
Taken together, our findings suggest that SVR10 and BPG2 are functionally related
with VAR2, likely through their potential roles in regulating chloroplast protein
homeostasis, and both SVR10 and BPG2 are required for efficient thylakoid protein
complex assembly and photosynthesis.
PMID- 26435533
TI - Exercise level before pregnancy and engaging in high-impact sports reduce the
risk of pelvic girdle pain: a population-based cohort study of 39 184 women.
AB - OBJECTIVE: To examine whether an association exists between exercise levels pre
pregnancy and pelvic girdle pain in pregnancy. Pelvic girdle pain in pregnancy
has been associated with physical inactivity, a risk factor for adverse pregnancy
outcomes. METHODS: We used data from a population-based cohort study including 39
184 nulliparous women with a singleton pregnancy enrolled in the Norwegian Mother
and Child Cohort study. Pre-pregnancy exercise frequency and types were assessed
by questionnaire in pregnancy week 17. Pelvic girdle pain, defined as combined
pain in the anterior pelvis and in the posterior pelvis bilaterally, was self
reported in pregnancy week 30. Multivariable Poisson regression estimated risks
of pelvic girdle pain associated with pre-pregnancy exercise. We examined a dose
response association of prepregnancy exercise frequency using restricted cubic
splines. A test for non-linearity was also conducted. Final models were adjusted
for pre-pregnancy BMI, age, education, history of low back pain and history of
depression. RESULTS: 4069 women (10.4%) reported pelvic girdle pain in pregnancy
and the prevalence among women who were non-exercisers prepregnancy was 12.5%.
There was a non-linear association for pre-pregnancy exercise and risk of pelvic
girdle pain (test for non-linearity, p=0.003). Compared to non-exercisers, women
exercising 3-5 times weekly pre-pregnancy had a 14% lower risk of developing
pelvic girdle pain in pregnancy (aRR 0.86, 95% CI 0.77 to 0.96). Taking part in
high-impact exercises such as running, jogging, orienteering, ballgames, netball
games and high-impact aerobics were associated with less risk of pelvic girdle
pain. SUMMARY: Women who exercise regularly and engage in high-impact exercises
before the first pregnancy may have a reduced risk of pelvic girdle pain in
pregnancy.
PMID- 26435534
TI - Validation of web-based, multiple 24-h recalls combined with nutritional
supplement intake questionnaires against nitrogen excretions to determine protein
intake in Dutch elite athletes.
AB - Information on dietary composition is vitally important for elite athletes to
optimise their performance and recovery, which requires valid tools. The aim of
the present study was to investigate the validity of assessing protein intake
using three web-based 24-h recalls and questionnaires, by comparing these with
three urinary N excretions on the same day. A total of forty-seven Dutch elite
top athletes, both disabled and non-disabled, aged between 18 and 35 years, with
a BMI of 17.5-31 kg/m2, exercising >12 h/week were recruited. Estimated mean
dietary protein intake was 109.6 (sd 33.0) g/d by recalls and questionnaires v.
141.3 (sd 38.2) g/d based on N excretions in urine; the difference was 25.5 (sd
21.3) % between the methods (P<0.05). We found a reasonably good association
between methods for protein intake of 0.65 (95 % CI 0.45, 0.79). On an individual
level, under-reporting was larger with higher protein intakes than with lower
intakes. No significant differences were found in reporting absolute differences
between subcategories (sex, under-reporting, BMI, collection of recalls within a
certain amount of time and using protein supplements or not). In conclusion,
combined, multiple, 24-h recalls and questionnaires underestimated protein intake
in these young elite athletes more than that reported for non-athlete
populations. The method proved to be suitable for ranking athletes according to
their protein intake as needed in epidemiological studies. On an individual
level, the magnitude of underestimation was about equal for all athletes except
for those with very high protein intakes.
PMID- 26435535
TI - Tuning B cell responsiveness by antigen receptor isotype.
PMID- 26435536
TI - Screening for peripheral neuropathy and peripheral arterial disease in persons
with diabetes mellitus in a Nigerian University Teaching Hospital.
AB - BACKGROUND: Identifying the risk factors for diabetes mellitus related foot
ulceration would save more limbs from amputation. This report focuses on the
determining the burden of peripheral arterial disease and neuropathy in persons
with diabetes mellitus (DM). METHODS: This is a descriptive study carried out in
the Diabetic Clinic of the Lagos State University Teaching Hospital in patients
with DM who had no past/present history of foot ulceration. Biothesiometry was
employed and ankle brachial pressure indices were measured to evaluate for
neuropathy and peripheral arterial disease (PAD) respectively. RESULTS: A total
of 225 persons living with DM who met inclusion criteria were recruited
consecutively over a 3 months period. Age range was 28-87 years with the mean
[61.4 (10.8)] and median (63) years respectively. Patients symptomatic for
neuropathy and PAD were 37 and 40 % respectively of the study population. An
older age of >60 years and poor glycaemic control were potential predictors of
neuropathy. Neuropathy and PAD occurred commonly in the seventh decade of life.
CONCLUSION: Given the fairly high proportions of neuropathy and PAD in our
patients with DM, we recommend that they be routinely examined in persons with
DM.
PMID- 26435537
TI - Effects of Sleeve Gastrectomy and Gastric Bypass on Postprandial Lipid Profile in
Obese Type 2 Diabetic Patients: a 2-Year Follow-up.
AB - BACKGROUND: Bariatric surgery (BS) is known to favorably impact fasting lipid
profile. Fasting and postprandial lipids were evaluated before and 2 years after
BS in obese type 2 diabetic (T2DM) patients. METHODS: A prospective study was
conducted in 19 obese T2DM patients: ten undergoing sleeve gastrectomy (SG) and
nine undergoing Roux-en-Y gastric bypass (RYGB). Before and 2 years after BS,
clinical parameters and the response of lipid and incretin hormones to a mixed
meal (MM) were assessed. RESULTS: The two groups had similar characteristics at
baseline. After BS, weight loss was similar in the two groups (p <= 0.01).
Fasting glucose, insulin, and triglycerides decreased while HDL cholesterol
increased in a similar way (p < 0.05); in contrast, fasting LDL cholesterol
decreased only after RYGB (p < 0.05). Post-meal glucose concentrations decreased
while early insulin response significantly improved after both procedures (p <
0.001 for both). Postprandial triglycerides decreased after both procedures (p <
0.05) while postprandial LDL cholesterol decreased only after RYGB (p < 0.05).
Meal-GLP-1 increased postoperatively in both groups although to a greater extent
after RYGB (p < 0.001 vs. SG). GIP decreased after both procedures, especially
after RYGB (p = 0.003). At multivariate analysis, GLP-1 peak was the best
predictor of LDL reduction (beta = -0.552, p = 0.039) while the improvement of
HOMA-IR (beta = 0.574, p = 0.014) and weight loss (beta = 0.418, p = 0.036)
predicted triglycerides reduction. CONCLUSIONS: Both surgical procedures markedly
reduce fasting and postprandial triglycerides and increase HDL cholesterol
levels. LDL cholesterol decreases only after RYGB through a mechanism likely
mediated by the restoration of GLP-1.
PMID- 26435541
TI - Reproductive ability of a cloned male detector dog and behavioral traits of its
offspring.
AB - In 2007, seven detector dogs were produced by somatic cell nuclear transfer using
one nuclear donor dog, then trained and certified as excellent detector dogs,
similar to their donor. In 2011, we crossed a cloned male and normal female by
natural breeding and produced ten offspring. In this study, we investigated the
puppies' temperaments, which we later compared with those of the cloned parent
male. The results show that the cloned male had normal reproductive abilities and
produced healthy offspring. All puppies completed narcotic detector dog training
with a success rate for selection of 60%. Although the litter of cloned males was
small in this study, a cloned male dog bred by natural mating produced puppies
that later successfully completed the training course for drug detection. In
conclusion, cloning an elite dog with superior genetic factors and breeding of
the cloned dog was found to be a useful method to efficiently procure detector
dogs.
PMID- 26435543
TI - Development and evaluation of a competitive enzyme-linked immunosorbent assay
using a monoclonal antibody for diagnosis of severe fever with thrombocytopenia
syndrome virus in bovine sera.
AB - Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus
(SFTSV), a phlebovirus in the family Bunyaviridae, is an emerging tick-borne
infectious disease that impacts humans. This disease manifests as a decreased
blood cell count and multi-organ failure, with a case-fatality rate of more than
12% in China. Because vaccines or antiviral drugs for the treatment of this
disease are not available, monitoring the SFTS circulation in animals and
controlling the tick-mammal cycle are important for preventing SFTS. Monoclonal
antibodies against the recombinant nucleoprotein of SFTSV were generated to
develop a competitive enzyme-linked immunosorbent assay (cELISA) for the
detection of antibodies against SFTSV infection in cattle. The specificity and
sensitivity of cELISA was assessed by comparing the results of this assay to
those of an immunofluorescence assay (IFA). The results of the cELISA using 416
field bovine serum samples and laboratory-immunized positive sera showed 98.1%
consistency with those of the IFA. The cELISA used in this study did not show
cross-reactivity with antisera against other viral cattle diseases. The cELISA
presented in this study can be applied to detect antibodies against SFTSV in
cattle.
PMID- 26435544
TI - Time-course changes of hippocalcin expression in the mouse hippocampus following
pilocarpine-induced status epilepticus.
AB - Hippocalcin participates in the maintenance of neuronal calcium homeostasis. In
the present study, we examined the time-course changes of neuronal degeneration
and hippocalcin protein level in the mouse hippocampus following pilocarpine
induced status epilepticus (SE). Marked neuronal degeneration was observed in the
hippocampus after SE in a time-dependent manner, although neuronal degeneration
differed according to the hippocampal subregions. Almost no hippocalcin
immunoreactivity was detected in the pyramidal neurons of the cornu ammonis 1
(CA1) region from 6 h after SE. However, many pyramidal neurons in the CA2 region
showed hippocalcin immunoreactivity until 24 h after SE. In the CA3 region, only
a few hippocalcin immunoreactive cells were observed at 12 h after SE, and almost
no hippocalcin immunoreactivity was observed in the pyramidal neurons from 24 h
after SE. Hippocalcin immunoreactivity in the polymorphic cells of the dentate
gyrus was markedly decreased from 6 h after SE. In addition, hippocalcin protein
level in the hippocampus began to decrease from 6 h after SE, and was
significantly decreased at 24 h and 48 h after pilocarpine-induced SE. These
results indicate that marked reduction of hippocalcin level may be closely
related to neuronal degeneration in the hippocampus following pilocarpine-induced
SE.
PMID- 26435545
TI - Choice of Model for Estimation of Adsorption Isotherm Parameters in Gradient
Elution Preparative Liquid Chromatography.
AB - The inverse method is a numerical method for fast estimation of adsorption
isotherm parameters directly from a few overloaded elution profiles and it was
recently extended to adsorption isotherm acquisition in gradient elution
conditions. However, the inverse method in gradient elution is cumbersome due to
the complex adsorption isotherm models found in gradient elution. In this case,
physicochemically correct adsorption models have very long calculation times. The
aim of this study is to investigate the possibility of using a less complex
adsorption isotherm model, with fewer adjustable parameters, but with
preserved/acceptable predictive abilities. We found that equal or better
agreement between experimental and predicted elution profiles could be achieved
with less complex models. By being able to select a model with fewer adjustable
parameters, the calculation times can be reduced by at least a factor of 10.
PMID- 26435546
TI - Computational modeling and simulation of spall fracture in polycrystalline solids
by an atomistic-based interfacial zone model.
AB - The focus of this work is to investigate spall fracture in polycrystalline
materials under high-speed impact loading by using an atomistic-based interfacial
zone model. We illustrate that for polycrystalline materials, increases in the
potential energy ratio between grain boundaries and grains could cause a fracture
transition from intergranular to transgranular mode. We also found out that the
spall strength increases when there is a fracture transition from intergranular
to transgranular. In addition, analysis of grain size, crystal lattice
orientation and impact speed reveals that the spall strength increases as grain
size or impact speed increases.
PMID- 26435547
TI - Wives' and Husbands' Nonfamily Experiences and First-Birth Timing.
PMID- 26435548
TI - Institutionalization of Migration Policy Frameworks in Armenia, Azerbaijan and
Georgia.
AB - This article is a comparative study of the institutionalization of the migration
policy frameworks of post-Soviet states Armenia, Azerbaijan and Georgia since the
collapse of the Soviet Union in 1991. All three countries share common historical
legacies: a Soviet past, wars and conflicts, unemployment, high emigration, and
commitment to integration into European bodies. To what extent do the migration
policies of these three countries (driven by contextual forces, i.e. domestic
challenges) address country-specific migration dynamics? Or are they imposed by
the European Union? In which dimensions have the national policies on migration
of Armenia, Azerbaijan and Georgia evolved, and around which issues have they
converged or diverged? Have these trends led to an integration of migration
policymaking at the regional level in the South Caucasus?
PMID- 26435549
TI - The solubility and site preference of Fe3+ in Li7-3x Fe x La3Zr2O12 garnets.
AB - A series of Fe3+-bearing Li7La3Zr2O12 (LLZO) garnets was synthesized using solid
state synthesis methods. The synthetic products were characterized
compositionally using electron microprobe analysis and inductively coupled plasma
optical emission spectroscopy (ICP-OES) and structurally using X-ray powder
diffraction and 57Fe Mossbauer spectroscopy. A maximum of about 0.25 Fe3+ pfu
could be incorporated in Li7-3x Fe x La3Zr2O12 garnet solid solutions. At Fe3+
concentrations lower than about 0.16 pfu, both tetragonal and cubic garnets were
obtained in the synthesis experiments. X-ray powder diffraction analysis showed
only a garnet phase for syntheses with starting materials having intended Fe3+
contents lower than 0.52 Fe3+ pfu. Back-scattered electron images made with an
electron microprobe also showed no phase other than garnet for these
compositions. The lattice parameter, a0, for all solid-solution garnets is
similar with a value of a0~12.98 A regardless of the amount of Fe3+. 57Fe
Mossbauer spectroscopic measurements indicate the presence of poorly- or nano
crystalline FeLaO3 in syntheses with Fe3+ contents greater than 0.16 Fe3+ pfu.
The composition of different phase pure Li7-3x Fe x La3Zr2O12 garnets, as
determined by electron microprobe (Fe, La, Zr) and ICP-OES (Li) measurements,
give Li6.89Fe0.03La3.05Zr2.01O12, Li6.66Fe0.06La3.06Zr2.01O12,
Li6.54Fe0.12La3.01Zr1.98O12, and Li6.19Fe0.19La3.02Zr2.04O12. The 57Fe Mossbauer
spectrum of cubic Li6.54Fe0.12La3.01Zr1.98O12 garnet indicates that most Fe3+
occurs at the special crystallographic 24d position, which is the standard
tetrahedrally coordinated site in garnet. Fe3+ in smaller amounts occurs at a
general 96h site, which is only present for certain Li-oxide garnets, and in
Li6.54Fe0.12La3.01Zr1.98O12 this Fe3+ has a distorted 4-fold coordination.
PMID- 26435550
TI - Developmental, Component-Based Model of Reading Fluency: An Investigation of
Predictors of Word-Reading Fluency, Text-Reading Fluency, and Reading
Comprehension.
AB - The primary goal was to expand our understanding of text reading fluency
(efficiency or automaticity)-how its relation to other constructs (e.g., word
reading fluency and reading comprehension) changes over time and how it is
different from word reading fluency and reading comprehension. We examined (1)
developmentally changing relations among word reading fluency, listening
comprehension, text reading fluency, and reading comprehension; (2) the relation
of reading comprehension to text reading fluency; (3) unique emergent literacy
predictors (i.e., phonological awareness, orthographic awareness, morphological
awareness, letter name knowledge, vocabulary) of text reading fluency vs. word
reading fluency; and (4) unique language and cognitive predictors (e.g.,
vocabulary, grammatical knowledge, theory of mind) of text reading fluency vs.
reading comprehension. These questions were addressed using longitudinal data
(two timepoints; Mean age = 5;24 & 6;08) from Korean-speaking children (N = 143).
Results showed that listening comprehension was related to text reading fluency
at time 2, but not at time 1. At both times text reading fluency was related to
reading comprehension, and reading comprehension was related to text reading
fluency over and above word reading fluency and listening comprehension.
Orthographic awareness was related to text reading fluency over and above other
emergent literacy skills and word reading fluency. Vocabulary and grammatical
knowledge were independently related to text reading fluency and reading
comprehension whereas theory of mind was related to reading comprehension, but
not text reading fluency. These results reveal developmental nature of relations
and mechanism of text reading fluency in reading development.
PMID- 26435551
TI - Click chemistry oligomerisation of azido-alkyne-functionalised galactose accesses
triazole-linked linear oligomers and macrocycles that inhibit Trypanosoma cruzi
macrophage invasion.
AB - Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-beta-d
galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and
linear triazole-linked oligomers, with individual compounds up to d.p. 5
isolable, along with mixed larger oligomers. The linear compounds resolve en bloc
from the cyclic materials by RP HPLC, but are separable by gel permeation
chromatography. The triazole-linked oligomers-pseudo-galactooligomers-were
demonstrated to be acceptor substrates for the multi-copy cell surface trans
sialidase of the human parasite Trypanosoma cruzi. In addition, these multivalent
TcTS ligands were able to block macrophage invasion by T. cruzi.
PMID- 26435552
TI - Predicting the evolution of social networks with life cycle events.
AB - This paper presents a model of social network evolution, to predict and simulate
changes in social networks induced by lifecycle events. We argue that social
networks change with lifecycle events, and we extend a model of friendship
selection to incorporate these dynamics of personal social networks. The model
uses theories of homophily and reciprocity and is formulated in a random utility
maximization framework to predict the formation of social ties between
individuals in the population. It is then extended to predict the evolution of
social networks in response to life cycle events. The model is estimated using
attribute data of a national sample and an event-based retrospective dataset
collected in 2009 and 2011 respectively. Findings suggest that homophily has a
strong effect on the formation of new ties. However, heterophily also plays a
role in maintaining existing ties. Although the motivation of this research stems
from incorporating social network dynamics in large-scale travel behaviour micro
simulation models, the research can be used in a variety of fields for similar
purposes.
PMID- 26435553
TI - The Infrared Spectra of Polycyclic Aromatic Hydrocarbons with Excess Peripheral H
Atoms (Hn-PAHs) and their Relation to the 3.4 and 6.9 um PAH Emission Features.
AB - Polycyclic aromatic hydrocarbons (PAHs) are likely responsible for the family of
infrared emission features seen in a wide variety of astrophysical environments.
A potentially important subclass of these materials are PAHs whose edges contain
excess H atoms (Hn-PAHs). This type of compound may be present in space, but it
has been difficult to assess this possibility because of a lack of suitable
laboratory spectra to assist with analysis of astronomical data. We present 4000
500 cm-1 (2.5-20 um) infrared spectra of 23 Hn-PAHs and related molecules
isolated in argon matrices under conditions suitable for interpretation of
astronomical data. Spectra of molecules with mixed aromatic and aliphatic domains
show characteristics that distinguish them from fully aromatic PAH equivalents.
Two major changes occur as PAHs become more hydrogenated: (1) aromatic C-H
stretching bands near 3.3 um weaken and are replaced with stronger aliphatic
bands near 3.4 um, and (2) aromatic C-H out-of-plane bending mode bands in the 11
15 um region shift and weaken concurrent with growth of a strong aliphatic -CH2
deformation mode near 6.9 um. Implications for interpreting astronomical spectra
are discussed with emphasis on the 3.4 and 6.9 um features. Laboratory data is
compared with emission spectra from IRAS 21282+5050, an object with normal PAH
emission features, and IRAS 22272+5435 and IRAS 0496+3429, two protoplanetary
nebulae with abnormally large 3.4 um features. We show that 'normal' PAH emission
objects contain relatively few Hn-PAHs in their emitter populations, but less
evolved protoplanetary nebulae may contain significant abundances of these
molecules.
PMID- 26435554
TI - Thermophysical properties of two ammonium-based protic ionic liquids.
AB - Experimental data for density, viscosity, refractive index and surface tension
are reported, for the first time, in the temperature range between 288.15 K and
353.15 K and at atmospheric pressure for two protic ionic liquids, namely 2
(dimethylamino)-N,N-dimethylethan-1-ammonium acetate, [N11{2(N11)}H][CH3CO2], and
N-ethyl-N,N-dimethylammonium phenylacetate, [N112H][C7H7CO2]. The effect of the
anion aromaticity and the cation's aliphatic tails on the studied properties is
discussed. From the measured properties temperature dependency the derived
properties, such as the isobaric thermal expansion coefficient, the surface
entropy and enthalpy, and the critical temperature, were estimated.
PMID- 26435556
TI - Roof Instability: What Reportable Noninjury Roof Falls in Underground Coal Mines
Can Tell Us.
PMID- 26435555
TI - Cross-Sectional Predictors of Sexual Assault Perpetration in a Community Sample
of Single African American and Caucasian Men.
AB - Computer-assisted self-interviews were completed with a random sample of 163
unmarried Caucasian and African American men in a large metropolitan area. Almost
a quarter (24.5%) of these men acknowledged committing an act since the age of 14
that met standard legal definitions of attempted or completed rape; an additional
39% had committed another type of sexual assault involving forced sexual contact
or verbal coercion. An expanded version of the Malamuth et al. [1991] confluence
model was examined using path analysis. The number of sexual assaults perpetrated
by participants was associated with the direct or indirect effects of childhood
sexual abuse, adolescent delinquency, alcohol problems, sexual dominance,
positive attitudes about casual sexual relationships, and pressure from peers to
engage in sexual relationships. Additionally, empathy buffered the relationship
between sexual dominance and perpetration. The pattern of results was highly
similar for African American and Caucasian men. The implications of these
findings for sexual assault measurement are discussed and suggestions are made
for alternative treatment programs.
PMID- 26435557
TI - Integration of vertical and in-seam horizontal well production analyses with
stochastic geostatistical algorithms to estimate pre-mining methane drainage
efficiency from coal seams: Blue Creek seam, Alabama.
AB - Coal seam degasification and its efficiency are directly related to the safety of
coal mining. Degasification activities in the Black Warrior basin started in the
early 1980s by using vertical boreholes. Although the Blue Creek seam, which is
part of the Mary Lee coal group, has been the main seam of interest for coal
mining, vertical wellbores have also been completed in the Pratt, Mary Lee, and
Black Creek coal groups of the Upper Pottsville formation to degasify multiple
seams. Currently, the Blue Creek seam is further degasified 2-3 years in advance
of mining using in-seam horizontal boreholes to ensure safe mining. The studied
location in this work is located between Tuscaloosa and Jefferson counties in
Alabama and was degasified using 81 vertical boreholes, some of which are still
active. When the current long mine expanded its operation into this area in 2009,
horizontal boreholes were also drilled in advance of mining for further
degasification of only the Blue Creek seam to ensure a safe and a productive
operation. This paper presents an integrated study and a methodology to combine
history matching results from vertical boreholes with production modeling of
horizontal boreholes using geostatistical simulation to evaluate spatial
effectiveness of in-seam boreholes in reducing gas-in-place (GIP). Results in
this study showed that in-seam wells' boreholes had an estimated effective
drainage area of 2050 acres with cumulative production of 604 MMscf methane
during ~2 years of operation. With horizontal borehole production, GIP in the
Blue Creek seam decreased from an average of 1.52 MMscf to 1.23 MMscf per acre.
It was also shown that effective gas flow capacity, which was independently
modeled using vertical borehole data, affected horizontal borehole production.
GIP and effective gas flow capacity of coal seam gas were also used to predict
remaining gas potential for the Blue Creek seam.
PMID- 26435558
TI - Geostatistical modeling of the gas emission zone and its in-place gas content for
Pittsburgh-seam mines using sequential Gaussian simulation.
AB - Determination of the size of the gas emission zone, the locations of gas sources
within, and especially the amount of gas retained in those zones is one of the
most important steps for designing a successful methane control strategy and an
efficient ventilation system in longwall coal mining. The formation of the gas
emission zone and the potential amount of gas-in-place (GIP) that might be
available for migration into a mine are factors of local geology and rock
properties that usually show spatial variability in continuity and may also show
geometric anisotropy. Geostatistical methods are used here for modeling and
prediction of gas amounts and for assessing their associated uncertainty in gas
emission zones of longwall mines for methane control. This study used core data
obtained from 276 vertical exploration boreholes drilled from the surface to the
bottom of the Pittsburgh coal seam in a mining district in the Northern
Appalachian basin. After identifying important coal and non-coal layers for the
gas emission zone, univariate statistical and semivariogram analyses were
conducted for data from different formations to define the distribution and
continuity of various attributes. Sequential simulations performed stochastic
assessment of these attributes, such as gas content, strata thickness, and strata
displacement. These analyses were followed by calculations of gas-in-place and
their uncertainties in the Pittsburgh seam caved zone and fractured zone of
longwall mines in this mining district. Grid blanking was used to isolate the
volume over the actual panels from the entire modeled district and to calculate
gas amounts that were directly related to the emissions in longwall mines.
Results indicated that gas-in-place in the Pittsburgh seam, in the caved zone and
in the fractured zone, as well as displacements in major rock units, showed
spatial correlations that could be modeled and estimated using geostatistical
methods. This study showed that GIP volumes may change up to 3 MMscf per acre
and, in a multi-panel district, may total 9 Bcf of methane within the gas
emission zone. Therefore, ventilation and gas capture systems should be designed
accordingly. In addition, rock displacements within the gas emission zone are
spatially distributed. From an engineering and practical point of view, spatial
distributions of GIP and distributions of rock displacements should be correlated
with in-mine emissions and gob gas venthole productions.
PMID- 26435559
TI - Comprehensive Study on the Impact of the Cation Alkyl Side Chain Length on the
Solubility of Water in Ionic Liquids.
AB - A comprehensive study on the phase behaviour of two sets of ionic liquids (ILs)
and their interactions with water is here presented through combining
experimental and theoretical approaches. The impact of the alkyl side chain
length and the cation symmetry on the water solubility in the asymmetric [C N
1C1im][NTf2] and symmetric [C N-1C N-1im][NTf2] series of ILs (N up to 22), from
288.15 K to 318.15 K and at atmospheric pressure, was studied. The experimental
data reveal that the solubility of water in ILs with an asymmetric cation is
higher than in those with the symmetric isomer. Several trend shifts on the water
solubility as a function of the alkyl side chain length were identified, namely
at [C6C1im][NTf2] for asymmetric ILs and at [C4C4im][NTf2] and [C7C7im][NTf2] for
the symmetric ILs. To complement the experimental data and to further investigate
the molecular-level mechanisms behind the dissolution process, Density Functional
Theory calculations, using the Conductor-like Screening Model for Real Solvents
(COSMO-RS) and the Electrostatic potential-derived CHelpG, were performed. The
COSMO-RS model is able to qualitatively predict water solubility as function of
temperature and alkyl chain lengths of both symmetric and asymmetric cations.
Furthermore, the model is also capable to predict the somewhat higher water
solubility in the asymmetric cation, as well as the trend shift as function of
alkyl chain lengths experimentally observed. Both COSMO-RS and the electrostatic
potential-derived CHelpG show that the interactions of water and the IL cation
take place on the IL polar region, namely on the aromatic head and adjacent
methylene groups what explains the differences in water solubility observed for
cations with different chain lengths. Furthermore, the CHelpG calculations for
the isolated cations in the gas phase indicates that the trend shift of water
solubility as function of alkyl chain lengths and the difference of water
solubility in symmetric may also result from the partial positive charge
distribution/contribution of the cation.
PMID- 26435560
TI - The Parzen Window method: In terms of two vectors and one matrix.
AB - Pattern classification methods assign an object to one of several predefined
classes/categories based on features extracted from observed attributes of the
object (pattern). When L discriminatory features for the pattern can be
accurately determined, the pattern classification problem presents no difficulty.
However, precise identification of the relevant features for a classification
algorithm (classifier) to be able to categorize real world patterns without
errors is generally infeasible. In this case, the pattern classification problem
is often cast as devising a classifier that minimizes the misclassification rate.
One way of doing this is to consider both the pattern attributes and its class
label as random variables, estimate the posterior class probabilities for a given
pattern and then assign the pattern to the class/category for which the posterior
class probability value estimated is maximum. More often than not, the form of
the posterior class probabilities is unknown. The so-called Parzen Window
approach is widely employed to estimate class-conditional probability (class
specific probability) densities for a given pattern. These probability densities
can then be utilized to estimate the appropriate posterior class probabilities
for that pattern. However, the Parzen Window scheme can become computationally
impractical when the size of the training dataset is in the tens of thousands and
L is also large (a few hundred or more). Over the years, various schemes have
been suggested to ameliorate the computational drawback of the Parzen Window
approach, but the problem still remains outstanding and unresolved. In this
paper, we revisit the Parzen Window technique and introduce a novel approach that
may circumvent the aforementioned computational bottleneck. The current paper
presents the mathematical aspect of our idea. Practical realizations of the
proposed scheme will be given elsewhere.
PMID- 26435561
TI - Simultaneous optical flow and source estimation: Space-time discretization and
preconditioning.
AB - We consider the simultaneous estimation of an optical flow field and an
illumination source term in a movie sequence. The particular optical flow
equation is obtained by assuming that the image intensity is a conserved quantity
up to possible sources and sinks which represent varying illumination. We
formulate this problem as an energy minimization problem and propose a space-time
simultaneous discretization for the optimality system in saddle-point form. We
investigate a preconditioning strategy that renders the discrete system well
conditioned uniformly in the discretization resolution. Numerical experiments
complement the theory.
PMID- 26435562
TI - IMMIGRATION ENFORCEMENT AND MIXED-STATUS FAMILIES: THE EFFECTS OF RISK OF
DEPORTATION ON MEDICAID USE.
AB - As Congress priorities the immigration debate on increased border security, the
fate of an estimated 11 million undocumented citizens remains uncertain. Stuck in
between partisan politics and practical solutions are mixed-status families in
which some members of the family are U.S. citizens while other members are in the
country without proper authorization. This paper, examines the relationship
between risk of deportation and Medicaid use drawing from a nationally sample of
mothers from the Fragile Families and Child Wellbeing Survey. These data are then
merged with data from the U.S. Citizenship and Immigration Services to create a
contextual risk of deportation measure. Findings suggest that an increase in risk
of deportation is associated with a decrease in Medicaid use. The implications of
this work have tremendous impacts for health service providers and policy makers
interested in preventing and reducing health disparities in complex family
structures.
PMID- 26435563
TI - Distribution-free Inference of Zero-inated Binomial Data for Longitudinal
Studies.
AB - Count reponses with structural zeros are very common in medical and psychosocial
research, especially in alcohol and HIV research, and the zero-inflated poisson
(ZIP) and zero-inflated negative binomial (ZINB) models are widely used for
modeling such outcomes. However, as alcohol drinking outcomes such as days of
drinkings are counts within a given period, their distributions are bounded above
by an upper limit (total days in the period) and thus inherently follow a
binomial or zero-inflated binomial (ZIB) distribution, rather than a Poisson or
zero-inflated Poisson (ZIP) distribution, in the presence of structural zeros. In
this paper, we develop a new semiparametric approach for modeling zero-inflated
binomial (ZIB)-like count responses for cross-sectional as well as longitudinal
data. We illustrate this approach with both simulated and real study data.
PMID- 26435564
TI - Examining the complexity and variation of health care system distrust across
neighborhoods: Implications for preventive health care.
AB - PURPOSE: Recently, the institutional performance model has been used to explain
the increased distrust of health care system by arguing that distrust is a
function of individuals' perceptions on the quality of life in neighborhood and
social institutions. We examined (1) whether individuals assess two dimensions of
distrust consistently, (2) if the multilevel institutional performance model
explains the variation of distrust, and (3) how distrust patterns affect
preventive health care behaviors. METHODOLOGY: Using data from 9,497 respondents
in 914 census tracts (neighborhoods) in Philadelphia, we examined the patterns of
how individuals evaluate the competence and values distrust using the Multilevel
Latent Class Analysis (MLCA), and then investigated how neighborhood environment
factors are associated with distrust patterns. Finally, we used regression to
examine the relationships between distrust patterns and preventive health care.
FINDINGS: The MLCA identified four distrust patterns: Believers, Doubters,
Competence Skeptics, and Values Skeptics. We found that 55 % of the individuals
evaluated competence and values distrust coherently, with Believers reporting low
levels and Doubters having high levels of distrust. Competence and Values
Skeptics assessed distrust inconsistently. Believers were the least likely to
reside in socioeconomically disadvantaged and racially segregated neighborhoods
than other patterns. In contrast to Doubters, Believers were more likely to use
preventive health care, even after controlling for other socioeconomic factors
including insurance coverage. PRACTICAL IMPLICATIONS: Our findings suggest that
distrust patterns are function of neighborhood conditions and distrust patterns
are associated with preventive health care. This study provides important policy
implications for health care and future interventions.
PMID- 26435565
TI - Extracellular Vesicles as Biomarkers of Systemic Lupus Erythematosus.
AB - Systemic lupus erythematosus is an autoimmune disease that predominantly affects
women and typically manifests in multiple organs. The damage caused by this
disorder is characterized by a chronic inflammatory state. Extracellular vesicles
(EVs), including microvesicles (also known as microparticles), apoptotic bodies,
and exosomes, are recognized vehicles of intercellular communication, carrying
autoantigens, cytokines, and surface receptors. Therefore, the evidence of EVs
and their cargo as biomarkers of autoimmune disease is rapidly expanding. This
review will focus on biogenesis of extracellular vesicles, their
pathophysiological roles, and their potential as biomarkers and therapeutics in
inflammatory disease, especially in systemic lupus erythematosus.
PMID- 26435566
TI - Influence of GSTM1, GSTT1, and GSTP1 Polymorphisms on Type 2 Diabetes Mellitus
and Diabetic Sensorimotor Peripheral Neuropathy Risk.
AB - BACKGROUND AND AIMS: Diabetic neuropathy is a frequent complication of type 2
diabetes mellitus (T2DM). Genetic susceptibility and oxidative stress may play a
role in the appearance of T2DM and diabetic neuropathy. We investigated the
relation between polymorphism in genes related to oxidative stress such as GSTM1,
GSTT1, and GSTP1 and the presence of T2DM and diabetic neuropathy (DN). METHODS:
Samples were collected from 84 patients with T2DM (42 patients with DN and 42
patients without DN) and 98 healthy controls and genotyped by using polymerase
chain reaction and restriction fragment length polymorphism method. RESULTS:
GSTP1 Ile105Val polymorphism was associated with the risk of developing T2DM (p =
0.05) but not with the risk of developing DN in diabetic cases. GSTM1 and GSTT1
gene polymorphisms were associated with neither the risk of developing T2DM nor
the risk of DN occurrence in diabetic patients. No association was observed
between the patients with T2DM and DSPN (diabetic sensorimotor peripheral
neuropathy) and T2DM without DSPN regarding investigated polymorphism.
CONCLUSION: Our data suggest that GSTP1 gene polymorphisms may contribute to the
development of T2DM in Romanian population. GSTM1, GSTT1, and GSTP1 gene
polymorphisms are not associated with susceptibility of developing diabetic
neuropathy in T2DM patients.
PMID- 26435567
TI - Plasma Interleukin-37 Is Elevated in Patients with Rheumatoid Arthritis: Its
Correlation with Disease Activity and Th1/Th2/Th17-Related Cytokines.
AB - Interleukin- (IL-) 37 is a novel anti-inflammatory cytokine that suppresses
immune response and inflammation. This study was performed to determine whether
IL-37 was elevated in patients with rheumatoid arthritis (RA) and investigate the
correlation between IL-37 level and disease activity and the concentration of
Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity,
including the 28-joint disease activity score (DAS28) and C-reactive protein
(CRP), were collected in 34 RA patients and 34 age- and sex-matched healthy
controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-alpha, IL
1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM
CSF, IFN-gamma, MCP-1, and MIP-1beta were analyzed using the Bio-Plex suspension
array system. It was found that IL-37 levels were elevated markedly in RA
patients and almost undetectable in healthy controls. In addition, IL-37 levels
in patients with active RA were significantly enhanced as compared with those in
patients of remission. More importantly, IL-37 showed a significant correlation
with disease activity (DAS28) and IL-4, IL-7, IL-10, IL-12, and IL-13
concentrations in RA patients. These findings suggest that IL-37 plays an
important role in the pathogenesis of RA and may prove to be a potential
biomarker of active RA.
PMID- 26435568
TI - Identification of Circulating miRNAs in a Mouse Model of Nerve Allograft
Transplantation under FK506 Immunosuppression by Illumina Small RNA Deep
Sequencing.
AB - BACKGROUND: This study aimed to establish the expression profile of circulating
microRNAs (miRNAs) during nerve allotransplantation in the presence and absence
of FK506 immunosuppression. METHODS: A 1 cm BALB/c donor sciatic nerve graft was
transplanted into the sciatic nerve gaps created in recipient C57BL/6 mice with
or without daily FK506 immunosuppression [1 mg/(kg.d)]. At 3, 7, and 14 d after
nerve allotransplantation, serum samples were collected for miRNA expression
analysis by Illumina small RNA deep sequencing. RESULTS: Sequence analysis showed
that the dominant size of circulating small RNAs after nerve allotransplantation
was 22 nucleotides, followed by 23-nucleotide sequences. Nine upregulated
circulating miRNAs (let-7e-5p, miR-101a-3p, miR-151-5p, miR-181a-5p, miR-204-5p,
miR-340-5p, miR-381-3p, miR-411-5p, miR-9-5p, and miR-219-2-3p) were identified
at 3 d, but none was identified at 7 or 14 d. Among them, miR-9-5p had the
highest fold-change of >50-fold, followed by miR-340-5p with 38.8-fold. The
presence of these nine miRNAs was not significant at 7 and 14 d after nerve
allotransplantation with or without immunosuppression, showing that these miRNAs
are not ideal biomarkers for monitoring rejection of deep-buried nerve
allografts, a response usually observed later. CONCLUSIONS: We identified nine
upregulated circulating miRNAs, which may have a biological function,
particularly during the early stages after nerve allotransplantation under FK506
immunosuppression.
PMID- 26435570
TI - Evaluating the impacts of new walking and cycling infrastructure on carbon
dioxide emissions from motorized travel: a controlled longitudinal study.
AB - Walking and cycling is widely assumed to substitute for at least some motorized
travel and thereby reduce energy use and carbon dioxide (CO2) emissions. While
the evidence suggests that a supportive built environment may be needed to
promote walking and cycling, it is unclear whether and how interventions in the
built environment that attract walkers and cyclists may reduce transport CO2
emissions. Our aim was therefore to evaluate the effects of providing new
infrastructure for walking and cycling on CO2 emissions from motorised travel. A
cohort of 1849 adults completed questionnaires at baseline (2010) and one-year
follow-up (2011), before and after the construction of new high-quality routes
provided as part of the Sustrans Connect2 programme in three UK municipalities. A
second cohort of 1510 adults completed questionnaires at baseline and two-year
follow-up (2012). The participants reported their past-week travel behaviour and
car characteristics from which CO2 emissions by mode and purpose were derived
using methods described previously. A set of exposure measures of proximity to
and use of the new routes were derived. Overall transport CO2 emissions decreased
slightly over the study period, consistent with a secular trend in the case study
regions. As found previously the new infrastructure was well used at one- and two
year follow-up, and was associated with population-level increases in walking,
cycling and physical activity at two-year follow-up. However, these effects did
not translate into sizeable CO2 effects as neither living near the infrastructure
nor using it predicted changes in CO2 emissions from motorised travel, either
overall or disaggregated by journey purpose. This lack of a discernible effect on
travel CO2 emissions are consistent with an interpretation that some of those
living nearer the infrastructure may simply have changed where they walked or
cycled, while others may have walked or cycled more but few, if any, may have
substituted active for motorised modes of travel as a result of the
interventions. While the findings to date cannot exclude the possibility of small
effects of the new routes on CO2 emissions, a more comprehensive approach of a
higher 'dosage' of active travel promotion linked with policies targeted at mode
shift away from private motorized transport (such as urban car restraint and
parking pricing, car sharing/pooling for travel to work, integrating bike sharing
into public transport system) may be needed to achieve the substantial CO2
savings needed to meet climate change mitigation and energy security goals.
PMID- 26435569
TI - Optimal Vitamin D Supplementation Levels for Cardiovascular Disease Protection.
AB - First described in relation to musculoskeletal disease, there is accumulating
data to suggest that vitamin D may play an important role in cardiovascular
disease (CVD). In this review we aim to provide an overview of the role of
vitamin D status as both a marker of and potentially causative agent of
hypertension, coronary artery disease, heart failure, atrial fibrillation,
stroke, and peripheral vascular disease. The role of vitamin D levels as a
disease marker for all-cause mortality is also discussed. We review the current
knowledge gathered from experimental studies, observational studies, randomised
controlled trials, and subsequent systematic reviews in order to suggest the
optimal vitamin D level for CVD protection.
PMID- 26435571
TI - Ten years of invasion: Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) in
Britain.
AB - 1. Harmonia axyridis was first recorded in Britain in 2004. Two subsequent
earlier records were received from 2003. 2. The UK Ladybird Survey, a citizen
science initiative involving online recording, was launched in 2005 to encourage
people across Britain to track the spread of H. axyridis. Tens of thousands of
people have provided records of H. axyridis and other species of ladybirds,
creating an invaluable dataset for large-scale and long-term research. Declines
in the distribution of seven (of eight assessed) native species of ladybird have
been demonstrated, and correlated with the arrival of H. axyridis, using the
records collated through the UK Ladybird Survey. 3. Experimental research and
field surveys have also contributed to our understanding of the ecology of H.
axyridis and particularly the process of invasion. Harmonia axyridis arrived in
Britain through dispersal and introduction events from regions in which it was
deliberately released as a biological control agent. The rapid spread of this
species has been attributed to its high natural dispersal capability by means of
both flight and anthropogenic transport. A number of factors have contributed to
the successful establishment and indeed dominance of this polymorphic species
within aphidophagous guilds, including high reproductive capacity, intra-guild
predation, eurytopic nature, high resistance to natural enemies within the
invaded range, and potentially phenotypic plasticity. 4. The global invasion by
H. axyridis and subsequent research on this species has contributed to the
general understanding of biological invasions.
PMID- 26435572
TI - Using Social Judgment Theory method to examine how experienced occupational
therapy driver assessors use information to make fitness-to-drive
recommendations.
AB - INTRODUCTION: As people with a range of disabilities strive to increase their
community mobility, occupational therapy driver assessors are increasingly
required to make complex recommendations regarding fitness-to-drive. However,
very little is known about how therapists use information to make decisions. The
aim of this study was to model how experienced occupational therapy driver
assessors weight and combine information when making fitness-to-drive
recommendations and establish their level of decision agreement. METHOD: Using
Social Judgment Theory method, this study examined how 45 experienced
occupational therapy driver assessors from the UK, Australia and New Zealand made
fitness-to-drive recommendations for a series of 64 case scenarios. Participants
completed the task on a dedicated website, and data were analysed using
discriminant function analysis and an intraclass correlation coefficient.
RESULTS: Accounting for 87% of the variance, the cues central to the fitness-to
drive recommendations made by assessors are the client's physical skills,
cognitive and perceptual skills, road law craft skills, vehicle handling skills
and the number of driving instructor interventions. Agreement (consensus) between
fitness-to-drive recommendations was very high: intraclass correlation
coefficient = .97, 95% confidence interval .96-.98). CONCLUSION: Findings can be
used by both experienced and novice driver assessors to reflect on and strengthen
the fitness-to-drive recommendations made to clients.
PMID- 26435573
TI - Optimal firm growth under the threat of entry.
AB - The paper studies the incumbent-entrant problem in a fully dynamic setting. We
find that under an open-loop information structure the incumbent anticipates
entry by overinvesting, whereas in the Markov perfect equilibrium the incumbent
slightly underinvests in the period before the entry. The entry cost level where
entry accommodation passes into entry deterrence is lower in the Markov perfect
equilibrium. Further we find that the incumbent's capital stock level needed to
deter entry is hump shaped as a function of the entry time, whereas the
corresponding entry cost, where the entrant is indifferent between entry and non
entry, is U-shaped.
PMID- 26435574
TI - Thermophysical properties of phosphonium-based ionic liquids.
AB - Experimental data for density, viscosity, refractive index and surface tension of
four phosphonium-based ionic liquids were measured in the temperature range
between (288.15 and 353.15) K and at atmospheric pressure. The ionic liquids
considered include tri(isobutyl) methylphosphonium tosylate, [P i(444)1][Tos],
tri(butyl)methylphosphonium methylsulfate, [P4441][CH3SO4],
tri(butyl)ethylphosphonium diethylphosphate, [P4442][(C2H5O)2PO2], and
tetraoctylphosphonium bromide, [P8888][Br]. Additionally, derivative properties,
such as the isobaric thermal expansion coefficient, the surface thermodynamic
properties and the critical temperatures for the investigated ionic liquids were
also estimated and are presented and discussed. Group contribution methods were
evaluated and fitted to the density, viscosity and refractive index experimental
data.
PMID- 26435575
TI - Attitudinal, Experiential, and Situational Predictors of Sexual Assault
Perpetration.
AB - Past research demonstrates that sexual assault perpetration is caused by multiple
factors including attitudes, early experiences, and situational factors. In this
study, 343 college men described either a sexual assault they had committed or
their worst date. Discriminant function analysis indicated that attitudes about
gender roles and alcohol, number of consensual sex partners, how well the man
knew the woman, how isolated the setting was, alcohol consumption during the
event, the man's misperception of the woman's cues during the event, and prior
consensual sexual activity between the man and the woman discriminated between
sexual assaults and worst dates. Additionally, tactics used to obtain sex, self
attributions, the perceived seriousness of the assault, and the extent to which
it disrupted relationships with others significantly discriminated between men
who committed forced sexual contact, sexual coercion, and rape. These results
demonstrate the importance of considering both individual characteristics and
situational factors in theories and prevention activities.
PMID- 26435576
TI - Solution-Crystallization and Related Phenomena in 9,9-Dialkyl-Fluorene Polymers.
I. Crystalline Polymer-Solvent Compound Formation for Poly(9,9-dioctylfluorene).
AB - Polymer-solvent compound formation, occurring via co-crystallization of polymer
chains and selected small-molecular species, is demonstrated for the conjugated
polymer poly(9,9-dioctylfluorene) (PFO) and a range of organic solvents. The
resulting crystallization and gelation processes in PFO solutions are studied by
differential scanning calorimetry, with X-ray diffraction providing additional
information on the resulting microstructure. It is shown that PFO-solvent
compounds comprise an ultra-regular molecular-level arrangement of the
semiconducting polymer host and small-molecular solvent guest. Crystals form
following adoption of the planar-zigzag beta-phase chain conformation, which, due
to its geometry, creates periodic cavities that accommodate the ordered inclusion
of solvent molecules of matching volume. The findings are formalized in terms of
nonequilibrium temperature-composition phase diagrams. The potential applications
of these compounds and the new functionalities that they might enable are also
discussed. (c) 2015 The Authors. Journal of Polymer Science Part B: Polymer
Physics published by Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys.
2015, 53, 1481-1491.
PMID- 26435577
TI - Re-visioning Ultrasound through Women's Accounts of Pre-abortion Care in England.
AB - Feminist scholarship has demonstrated the importance of sustained critical
engagement with ultrasound visualizations of pregnant women's bodies. In response
to portrayals of these images as "objective" forms of knowledge about the fetus,
it has drawn attention to the social practices through which the meanings of
ultrasound are produced. This article makes a novel contribution to this project
by addressing an empirical context that has been neglected in the existing
feminist literature concerning ultrasound, namely, its use during pregnancies
that women decide to terminate. Drawing on semi-structured interviews with women
concerning their experiences of abortion in England, I explore how the meanings
of having an ultrasound prior to terminating a pregnancy are discursively
constructed. I argue that women's accounts complicate dominant representations of
ultrasound and that in so doing, they multiply the subject positions available to
pregnant women.
PMID- 26435578
TI - Applications of seaweed extracts in Australian agriculture: past, present and
future.
AB - A rapidly growing world population has highlighted the need to significantly
increase food production in the context of a world with accelerating soil and
water shortages as well as climatic stressors. This situation has generated new
interest in the application of liquid seaweed extracts because of their potent
plant growth-enhancing properties through metabolic benefits, triggering disease
response pathways and increasing stress tolerance. The basis for these benefits
is complex and poorly understood. Liquid seaweed extracts are complex and have
been demonstrated to possess novel mechanisms for increasing crop productivity.
The benefits of seaweed extracts to crops have previously been reviewed in the
context of the northern hemisphere, but not in the context of Australia, its
crops and unique stressors. This review considers the application of seaweed
extracts in Australian agriculture by (i) introducing the history of the
Australian liquid seaweed extract industry and (ii) focusing on evidence of
Australian research related to seaweed extract composition, plant growth
properties during plant establishment, pathogenic disease and new approaches to
phenotyping the biological efficacy of seaweed extracts. This type of research is
essential for future Australian agriculture to develop effective strategies for
the use of liquid seaweed extracts.
PMID- 26435579
TI - The suppressive effect of a commercial extract from Durvillaea potatorum and
Ascophyllum nodosum on infection of broccoli by Plasmodiophora brassicae.
AB - A sand solution technique demonstrated the capacity for a commercial seaweed
extract from Durvillaea potatorum and Ascophyllum nodosum (Seasol Commercial(r))
to significantly suppress infection of broccoli by Plasmodiophora brassicae. In
the primary stages of infection, the extract reduced the number of plasmodia
formed in the root hairs by 55 %. Later, in the secondary stages of infection,
the extract reduced plasmodia in the root cortical cells by up to 84 %. The
suppression of infection was found to be independent of the dilution of the
extract applied (1:25 and 1:500). The basis for these results is unlikely to be a
nutrient or pH effect since the extract had little impact on these parameters,
particularly at the lower dilution (1:200). Rather, we hypothesise that the
suppression of infection by the seaweed extract was due to its stimulation of
resistance mechanisms in the host, which is possibly related to laminarins in the
extract and/or the effect of exogenous growth regulators or undiscovered
molecules in the extract disrupting the infection process.
PMID- 26435580
TI - A Double Team Semantics for Generalized Quantifiers.
AB - We investigate extensions of dependence logic with generalized quantifiers. We
also introduce and investigate the notion of a generalized atom. We define a
system of semantics that can accommodate variants of dependence logic, possibly
extended with generalized quantifiers and generalized atoms, under the same
umbrella framework. The semantics is based on pairs of teams, or double teams. We
also devise a game-theoretic semantics equivalent to the double team semantics.
We make use of the double team semantics by defining a logic [Formula: see text]
which canonically fuses together two-variable dependence logic[Formula: see text]
and two-variable logic with counting quantifiers[Formula: see text]. We establish
that the satisfiability and finite satisfiability problems of [Formula: see text]
are complete for [Formula: see text].
PMID- 26435581
TI - Gravimetric Analysis of Particulate Matter using Air Samplers Housing Internal
Filtration Capsules.
AB - An evaluation was carried out to investigate the suitability of polyvinyl
chloride (PVC) internal capsules, housed within air sampling devices, for
gravimetric analysis of airborne particles collected in workplaces. Experiments
were carried out using blank PVC capsules and PVC capsules spiked with 0,1 - 4 mg
of National Institute of Standards and Technology Standard Reference Material(r)
(NIST SRM) 1648 (Urban Particulate Matter) and Arizona Road Dust (Air Cleaner
Test Dust). The capsules were housed within plastic closed-face cassette samplers
(CFCs). A method detection limit (MDL) of 0,075 mg per sample was estimated.
Precision Sr at 0,5 - 4 mg per sample was 0,031 and the estimated bias was 0,058.
Weight stability over 28 days was verified for both blanks and spiked capsules.
Independent laboratory testing on blanks and field samples verified long-term
weight stability as well as sampling and analysis precision and bias estimates.
An overall precision estimate Srt of 0,059 was obtained. An accuracy measure of
+/-15,5% was found for the gravimetric method using PVC internal capsules.
PMID- 26435582
TI - Microbial keratitis: a community eye health approach.
PMID- 26435583
TI - Diagnosing and managing microbial keratitis.
PMID- 26435584
TI - Distinguishing fungal and bacterial keratitis on clinical signs.
PMID- 26435585
TI - Taking a corneal scrape and making a diagnosis.
PMID- 26435586
TI - Performing a tarsorrhaphy.
PMID- 26435587
TI - Measuring the outcome of cataract surgery: the importance of the patient
perspective.
PMID- 26435589
TI - Electrosurgical units - how they work and how to use them safely.
PMID- 26435588
TI - School eye health - going beyond refractive errors.
PMID- 26435590
TI - Techniques for aseptic dressing and procedures.
PMID- 26435591
TI - Treatment coverage surveys as part of a trachoma control programme.
PMID- 26435592
TI - Vitamin D Deficiency: Is The Pandemic for Real?
PMID- 26435593
TI - Right to health: Challenges and Opportunities.
PMID- 26435594
TI - Essential Medicines: An Indian Perspective.
AB - The concept of defining essential medicines and establishing a list of them was
aimed to improve the availability of affordable medicines for the world's poor.
Access to essential medicines is a major determinant of health outcomes. Several
countries have made substantial progress towards increasing access to essential
medicines, but access to essential medicines in developing countries like India
is not adequate. In this review we have tried to present the Indian scenario in
respect to availability and accessibility of essential medicines over last one
decade. To enhance the credibility of Indian healthcare system, procurement and
delivery systems of essential medicines have to be strengthened through
government commitment, careful selection, adequate public sector financing,
efficient distribution systems, control on taxes and duties, and inculcating a
culture of rational use of medicines in current and future prescribers.
PMID- 26435595
TI - Three Sides of a Coin in the Life of People Living with HIV (PLWH).
AB - BACKGROUND: Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency
Syndrome (AIDS) is a global epidemic, a major challenge as a health care problem
of modern times. As the survival of life increases from the time of an HIV
positive diagnosis, growing concern for the quality of the life has been
extended. OBJECTIVES: To assess and correlate the coping, social support and
quality of life. MATERIALS AND METHODS: A descriptive cross-sectional study was
conducted at antiretroviral therapy (ART) clinic of AIIMS, New Delhi. The sample
comprised people living with HIV/AIDS (PLWHA) who were seropositive for last six
months. The tools used to assess the coping, social support and quality of life
were BREF COPE, MOS social support survey and WHO QOL-HIV BREF, respectively.
Permission was taken from the authors of the tools. The ethical permission was
taken from the center. The coping, social support and quality of life were
assessed and their association was observed. Data were analyzed using SPSS 17.
RESULTS: The most commonly used coping styles were acceptance and religion. The
social support used by most of PLWHA was tangible support and affectionate
support, while the least used support was positive social interaction. The lowest
quality of life is seen in social relations, followed by physical quality of
life. There was positive association seen between coping and quality of life as
well as social support and quality of life. CONCLUSION: There was positive
association between coping, social support and quality of life.
PMID- 26435596
TI - Evaluation of the Universal Immunization Program and Challenges in Coverage of
Migrant Children in Haridwar, Uttarakhand, India.
AB - BACKGROUND: Studies show that immunization among migrant children is poor. India
has a dropout rate of 17.7% between Bacillus Calmette-Guiotarin (BCG) and measles
(District Level Household Survey (DLHS)-3). Haridwar district had the highest
dropout rate of 27.4% from BCG to diphtheria, pertussis, and tetanus (DPT) 3
(DLHS-3) in Uttarakhand. We evaluated the Universal Immunization Programme (UIP)
among migrants in Haridwar in two blocks. MATERIALS AND METHODS: We developed
input, process, and output indicators on infrastructure, human resources, and
service delivery. A facility, session site and cross-sectional survey of 180
children were done and proportions for various indicators were estimated. We
determined factors associated with not taking vaccination using multivariate
analysis. RESULTS: We surveyed 11 cold chain centers, 25 subcenters, 14 sessions,
and interviewed 180 mothers. Dropouts were supposed to be tracked using
vaccination card counterfoils and tracking registers. The dropout rate from BCG
to DPT3 was 30%. Lack of knowledge (adjusted odds ratio (AOR) 6.6,95% confidence
interval (CI) 2.6-16.7), mother not being decision maker (AOR 4.0,95%CI 1.7-9.2),
lack of contact by Accredited Social Health Activist (ASHA; AOR 3.0,95%CI 1.1
7.7), not being given four post-vaccination messages (AOR 7.7, 95% CI 2.9-20.2),
and longer duration of stay in Haridwar (AOR 3.0 95% 1.9-7.6) were risk factors
for nonimmunization. The reasons stated by mothers included lack of awareness of
session site location (67%) and belief that child should only be vaccinated in
their resident district (43%). CONCLUSIONS: There was low immunization coverage
among migrants within adequate supervision, poor cold chain maintenance, and
improper tracking of dropouts. Mobile immunization teams, prelisting of migrant
children, and change in incentives of ASHAs for child tracking were needed. A
monitoring plan for sessions and cold chain needed enforcement.
PMID- 26435597
TI - An Epidemiological Study of Child Marriages in a Rural Community of Gujarat.
AB - CONTEXT: India has the maximum number of child marriages (CMs; < 18 years)
because of the size of its population, and in 47% of all marriages the bride is a
child. Children who are married at young age are exposed to multiple risks
pertaining to their physical, mental, and social health. AIMS: (i) To estimate
the prevalence of CM in rural population. (ii) To study the determinants and
health effects of CM. (iii) To assess the awareness among the married women
regarding the health implications of CM. SETTINGS AND DESIGN: Community-based
cross-sectional study conducted in Ardi village of Anand district. MATERIALS AND
METHODS: All the married women of the village were surveyed to find out the
prevalence of CM. For collection of other relevant information, only those women
having a married life of less than 10years were interviewed using semicoded and
pretested questionnaire. Data collected were analyzed using Statistical Package
for Social Sciences (SPSS) 17.0 software. STATISTICAL ANALYSIS USED: Proportions,
ratios, chi(2) test, and Fisher's exact test. RESULTS: The prevalence of CM was
found to be 71.5%. Caste and spouse's education were revealed as important
determinants for CM. CM was found to be significantly associated with mother's
age at birth of first child, delayed antenatal care (ANC), spontaneous abortion,
preterm delivery, low birth weight (LBW), health problems in new born baby,
faulty feeding practices, lack of knowledge regarding family welfare methods, and
health implications of CM. CONCLUSION: Exceptionally high prevalence of CM in
rural community and its serious health consequences warrant stricter enforcement
of legislation, better educational opportunities for girls, and easy access to
quality health services.
PMID- 26435598
TI - A Comparative Evaluation of Public Health Centers with Private Health Training
Centers on Primary Healthcare Parameters in India: a Study by Data Envelopment
Analysis Technique.
AB - BACKGROUND: The evaluation of primary healthcare services provided by health
training centers of a private medical college has not been studied in comparison
with government health facilities in Indian context. Data envelopment analysis
(DEA) is one such technique of operations research, which can be used on health
facilities for identifying efficient operating practices and strategies for
relatively efficient or inefficient health centers by calculating their
efficiency scores. MATERIALS AND METHODS: This study was carried out by DEA
technique by using basic radial models (constant ratio to scale (CRS)) in linear
programming via DEAOS free online Software among four decision making units
(DMUs; by comparing efficiency of two private health centers of a private medical
college of India with two public health centers) in district Muzaffarnagar of
state Uttar Pradesh. The input and output records of all these health facilities
(two from private and two from Government); for 6 months duration from 1(st) Jan
2014 to 1(st) July 2014 was taken for deciding their efficiency scores. RESULTS:
The efficiency scores of primary healthcare services in presence of doctors (100
vs 30%) and presence of health staff (100 vs 92%) were significantly better from
government health facilities as compared to private health facilities (P <
0.0001). CONCLUSIONS: The evaluation of primary healthcare services delivery by
DEA technique reveals that the government health facilities group were more
efficient in delivery of primary healthcare services as compared to private
training health facilities group, which can be further clarified in by more in
depth studies in future.
PMID- 26435599
TI - Risk Factors and Hospitalization Costs of Dementia Patients: Examining Race and
Gender Variations.
AB - AIMS: To examine the variation in risk factors and hospitalization costs among
four elderly dementia cohorts by race and gender. MATERIALS AND METHODS: The 2008
Tennessee Hospital Discharged database was examined. The prevalence, risk factors
and cost of inpatient care of dementia were examined for individuals aged 65
years and above, across the four race gender cohorts - white males (WM), black
males (BM), white females (WF), and black females (BF). RESULTS: 3.6% of patients
hospitalized in 2008 had dementia. Dementia was higher among females than males,
and higher among blacks than whites. Further, BF had higher prevalence of
dementia than WF; similarly, BM had a higher prevalence of dementia than WM.
Overall, six risk factors were associated with dementia for the entire sample
including HTN, DM, CKD, CHF, COPD, and stroke. These risk factors varied slightly
in predicting dementia by race and gender. Hospital costs were 14% higher among
dementia patients compared to non-dementia patients. CONCLUSIONS: There exist
significant race and gender disparities in prevalence of dementia. A greater
degree of co-morbidity, increased duration of hospital stay, and more frequent
hospitalizations, may result in a higher cost of inpatient dementia care.
Aggressive management of risk factors may subsequently reduce stroke and cost of
dementia care, especially in the black population. Race and gender dependent
milestones for management of these risk factors should be considered.
PMID- 26435600
TI - Sociodemographic Parameters of Esophageal Cancer in Northwest India: A Regional
Cancer Center Experience of 10 Years.
AB - BACKGROUND: Despite various advances in the treatment of Esophageal Cancer (EC),
being one of the least responsive tumors to cancer therapy, the overall prognosis
remains poor. Therefore, it is significant to understand various sociodemographic
factors associated with EC to find out various schemes for primary prevention of
the disease. MATERIALS AND METHODS: This is a retrospective analysis of medical
records of the EC patients registered in the regional cancer center of northwest
India from January 2003 to December 2012. The site of the disease and the
histology were also recorded in addition to the various sociodemographic
parameters. RESULTS: Out of 55,742 patients registered in our hospital; 3,667
were diagnosed to have EC. Male:female ratio was 1.15:1. The mean age was 54.6 +/
11.74 years; 66.15% of the patients were illiterate and 48.6% belonged to the
low socioeconomic status. Smoking and alcohol consumption were identified as risk
factors in 48 and 25.6% of the patients, respectively. CONCLUSIONS: The etiology
in majority of the patients is linked to tobacco and alcohol, thus, modification
of life style with limiting the use of addictions may be an effective strategy in
the prevention of this dreaded and mostly incurable disease.
PMID- 26435601
TI - Are we Underestimating the Real Burden of Malnutrition? An Experience From
Community-Based Study.
AB - BACKGROUND: Since the inception of childhood nutritional programs in India,
underweight has been taken to judge the nutritional status of children; but is it
a true indicator of overall prevalence of malnutrition in a community? OBJECTIVE:
To estimate the overall prevalence of malnutrition by using Composite Index of
Anthropometric Failure (CIAF) and to assess its usefulness over various
conventional anthropometric indicators among under 5 children residing in Agra
city. MATERIALS AND METHODS: A cross-sectional, community-based study was
conducted among under 5 years age children, from June 2012 to July 2013 in an
urban slum of Agra. Nutritional status was assessed using anthropometry and
clinical examination, and classified as per World Health Organization (WHO) 2006
Growth Standards and CIAF. RESULTS: Of the 458 children studied, 42.8% were
underweight, 41.9% had stunting, while 22.7% had wasting. However, 60.04% of
children were found to be malnourished as per the CIAF. Unlike three conventional
anthropometric indicators of malnutrition, CIAF was observed to have a much
consistent association with morbidity like diarrhea episodes in past 3 months
(odds ratio (OR) = 2.09), acute respiratory tract infection (ARI) episode in past
3 months (OR = 1.58), and any illness requiring hospitalization (OR = 1.29).
CONCLUSION: The CIAF should supplement the conventional indices of
malnourishment, to provide a single, aggregated figure of actual number of
undernourished children in a given population.
PMID- 26435602
TI - Hypertension in Pregnancy: A Community-Based Study.
AB - BACKGROUND: Hypertensive disorders during pregnancy occur in women with
preexisting primary or secondary chronic hypertension, and in women who develop
new-onset hypertension in the second half of pregnancy. The present study was
undertaken to study the prevalence and correlates of hypertension in pregnancy in
a rural block of Haryana. MATERIALS AND METHODS: This cross-sectional study was
carried out in the all 20 subcenters under Community Health Center (CHC) Chiri,
Block Lakhanmajra. All the pregnant women registered at the particular subcenter
at a point of time of visit were included in the study. Appropriate statistical
tests were used for analysis. RESULTS: A total of 931 pregnant women were
included in the present study. Prevalence of hypertension in pregnancy was found
to be 6.9%. Maternal age >=25 years, gestational period <=20 weeks, history of
cesarean section, history of preterm delivery, and history of hypertension in
previous pregnancy were found to be significantly associated with prevalence of
hypertension in pregnancy. CONCLUSION: Nearly one in 14 pregnant women in rural
areas of Haryana suffers from a hypertensive disorder of pregnancy. Early
diagnosis and treatment through regular antenatal checkup is a key factor to
prevent hypertensive disorders of pregnancy and its complications.
PMID- 26435603
TI - Prevalence and Risk Factors of Abuse among Community Dwelling Elderly of Guwahati
City, Assam.
AB - BACKGROUND: In spite of tremendous impact on health, elder abuse is still an
underreported and unrecognized issue. OBJECTIVES: To assess the prevalence of
abuse among community dwelling elderly and to identify the various risk factors.
MATERIALS AND METHODS: This community-based cross-sectional study was conducted
in 10 randomly selected wards of Guwahati city. A total of 331 elderly (60 years
and above) were interviewed. Abuse was screened by Hwalek-Sengstock Elder Abuse
Screening Test (H-S EAST). RESULTS: The study revealed 9.31% prevalence. Neglect
was the most common type of abuse reported. Age, sex, socioeconomic status,
living status, and functional status were found to be significantly associated
with abuse. CONCLUSION: Abuse is prevalent among elderly population.
PMID- 26435604
TI - Health Issues among Call Center Employees.
PMID- 26435605
TI - An Outbreak of Cholera due to Contaminated Water, Medak District, Andhra Pradesh,
India, 2013.
PMID- 26435606
TI - Guest Editorial.
PMID- 26435607
TI - Comparative Study of the Effect of Acid Etching on Enamel Surface Roughness
between Pumiced and Non-pumiced Teeth.
AB - BACKGROUND: The objective was to perform a comparative analysis of the effect of
acid etching on enamel roughness between pumiced and non-pumiced teeth. MATERIALS
AND METHODS: The sample was composed of 32 dental surfaces divided into two
groups: Group 1-16 surfaces having received pumice prophylaxis; and Group 2-16
surfaces not having received pumice prophylaxis. The teeth were kept in saline
until the first record of surface roughness prior to etching. For each surface, a
roughness graph was obtained through trials using a surface roughness tester.
This procedure was repeated two more times at different locations for a total of
three readings which, later, were converted in a mean value. The teeth were then
acid etched with a 37% phosphoric acid for 60 s, rinsed with water, air dried,
and tested with the roughness tester again using the same protocol described for
baseline. The Quantikov image analysis program was used to measure the length of
the graphs. The average value of the lengths was recorded for each surface before
and after etching. The increase in roughness caused by acid etching was
calculated and compared between groups. RESULTS: The mean increase in roughness
caused by the etching was 301 um (11.37%) in Group 1 and 214 um (8.33%) in Group
2. No statistically significant difference was found between samples with and
without pumice prophylaxis (P = 0.283). CONCLUSION: The present study showed that
the effect of acid etching on enamel roughness was not significantly affected by
prior pumice prophylaxis.
PMID- 26435608
TI - Comparing the Marginal Adaptation of Cold Ceramic and Mineral Trioxide Aggregate
by Means of Scanning Electron Microscope: An In vitro Study.
AB - BACKGROUND: Long-term success of endodontic surgeries is often influenced by the
type of root-end filling material (RFM). The aim of present study was to compare
the marginal adaptation of two different RFM, cold ceramic (CC) and mineral
trioxide aggregate (MTA), using scanning electron microscope (SEM). MATERIALS AND
METHODS: About 20 extracted human single-rooted teeth were collected and stored
into sodium hypochlorite 5.25%. The teeth were decronated from the cemento-enamel
junction to prepare 16 mm roots. The working length was measured, and 1/3 coronal
of the canal was prepared by Gates-Glidden drills. Apical flaring was followed by
K file size # 40-70 based on step back technique. After filling of the canals, 3
mm above the apex was cut at 90 degrees to the long axis. Furthermore, 3 mm of
the filling was removed from the apical part using the ultrasonic device. All of
the prepared specimens were divided into two groups and were retro filled by MTA
and CC. The roots were cut horizontally from 1 mm above the apical part, and
dentin-filling material interface was observed by SEM. Finally, the collected
data were analyzed by Mann-Whitney test and using SPSS software version 18 at a
significant level of 0.05. RESULTS: The mean interfacial adaptation was higher in
CC group. However, no significant differences were observed by statistical test
(P = 0.35). CONCLUSION: Both CC and MTA had similar marginal adaptation as RFM
however in vivo studies are recommended for better determination.
PMID- 26435609
TI - Meta-analysis of Failure and Survival Rate of Implant-supported Single Crowns,
Fixed Partial Denture, and Implant Tooth-supported Prostheses.
AB - BACKGROUND: Dental implants have become the most viable option for
rehabilitation. Although, many studies report the success of these
reconstructions using implants, a cumulative data about the various studies and
the failure rate still remain unaddressed. Therefore, the purpose of this
systematic review was to analyze these data and to derive the cumulative survival
rate of different implant-supported prosthesis. MATERIALS AND METHODS: Manual
searches followed by a MEDLINE search were conducted to select prospective and
retrospective cohort studies on single crowns (SCs), fixed partial denture (FPD),
and tooth implant connected prostheses with a mean follow-up time of minimum of 5
years. Random-effects Poisson's regression models have been used to obtain
summary estimates for implant failure and survival rates. RESULTS: Data were
extracted from the final selected 63 studies. In a meta-analysis of these
studies, the survival rate of SCs supported by implants (95% CI) was 96.363%, for
FPDs was 94.525% and implant tooth-supported prostheses was 91.27% after 5 years
of function. The cumulative failure rate per 100 FPD years of the SCs, FPDs, and
implant tooth-supported prostheses were 0.684, 0.881, and 1.514, respectively.
CONCLUSION: The study concludes high survival rates for implant-supported SCs
followed by implant-supported FPDs can be expected over an observation period of
5 years. However, tooth implant-supported prostheses can be provided if there are
certain limitations prohibiting the completely implant-supported prostheses.
PMID- 26435610
TI - An Analysis of Maxillary Anterior Teeth Dimensions for the Existence of Golden
Proportion: Clinical Study.
AB - BACKGROUND: Appearance of the face is a great concern to everyone, as it is a
significant part of self-image. The study analyzed the clinical crown dimensions
of the maxillary anterior teeth with respect to their apparent mesiodistal
widths, width-to-height ratio to determine whether golden proportion existed
among the South Indian population. MATERIALS AND METHODS: A total of 240
dentulous subjects were chosen for the study (120 males and 120 females) age
ranging between 18 and 28 years. Full face and anterior teeth images of the
subjects were made on specially designed device resembling a face-bow, mounted
onto the wall under a standard light source. The width and height of the
maxillary central incisors were measured on the stone casts using a digital
caliper. RESULTS: The mean perceived maxillary lateral incisor to central incisor
width ratio was 0.67 in males and 0.703 in females. The mean perceived maxillary
canine to lateral incisor width ratio was 0.744 in males and 0.714 in females.
The mean width-to-height ratio of the maxillary central incisor was 79.49% in
males and 79.197% in females. CONCLUSION: The golden proportion was not found
between perceived mesiodistal widths of maxillary central and lateral incisors
and nor between perceived mesiodistal widths of maxillary lateral incisors and
canines. In the majority of subjects, the width-to-height ratio of maxillary
central incisor was within 75-80%. There are no statistically significant
differences in maxillary anterior teeth proportions between males and females.
The results may serve as guidelines for treatment planning in restorative
dentistry and periodontal surgery.
PMID- 26435611
TI - Comparative Evaluation of Dimensional Accuracy of Elastomeric Impression
Materials when Treated with Autoclave, Microwave, and Chemical Disinfection.
AB - BACKGROUND: Impression materials during impression procedure often get infected
with various infectious diseases. Hence, disinfection of impression materials
with various disinfectants is advised to protect the dental team. Disinfection
can alter the dimensional accuracy of impression materials. The present study was
aimed to evaluate the dimensional accuracy of elastomeric impression materials
when treated with different disinfectants; autoclave, chemical, and microwave
method. MATERIALS AND METHODS: The impression materials used for the study were,
dentsply aquasil (addition silicone polyvinylsiloxane syringe and putty),
zetaplus (condensation silicone putty and light body), and impregum penta soft
(polyether). All impressions were made according to manufacturer's instructions.
Dimensional changes were measured before and after different disinfection
procedures. RESULT: Dentsply aquasil showed smallest dimensional change (
0.0046%) and impregum penta soft highest linear dimensional changes (-0.026%).
All the tested elastomeric impression materials showed some degree of dimensional
changes. CONCLUSION: The present study showed that all the disinfection
procedures produce minor dimensional changes of impression material. However, it
was within American Dental Association specification. Hence, steam autoclaving
and microwave method can be used as an alternative method to chemical
sterilization as an effective method.
PMID- 26435612
TI - A Comparative Evaluation of Adherence of Microorganism to Different Types of
Brackets: A Scanning Electron Microscopic Study.
AB - BACKGROUND: The purpose of this study was to evaluate and compare the adherence
of microorganism to different types of brackets using the scanning electron
microscope (SEM). A double-blinded study was undertaken to evaluate and adherence
of microorganisms to different types of brackets using SEM. MATERIALS AND
METHODS: At random, 12 patients reporting for treatment to the department of
Orthodontics VS Dental College and Hospital were selected. Four types of brackets
were included in the present study stainless steel, titanium, composite, and
ceramic. Brackets were bonded to teeth of the patient on all the four quadrants.
The teeth included for bonding were lateral incisor, canine, first premolar, and
second premolar. The brackets were left for 72 h. After 72 h brackets were
debonded, and they were evaluated by SEM for adherence of microorganism in the
slot and tie wings surface. The SEM images were graded, and the adherence of
microorganism to the brackets in the surfaces and the four different quadrants
were recorded. RESULTS: There is a significant difference in adherence of
microorganisms to the various types of brackets (P < 0.001) and the surfaces (P <
0.05) included in the study. However, there is no significance in the mean
adherence of microorganisms in the different quadrants (P > 0.05) included in the
study. The interaction of bracket/surface, bracket/quadrant, surface/quadrants
was analyzed, there was no significance of comparison of
bracket/surfaces/quadrant but the interaction of bracket/quadrant was found to be
significant (<0.011). The interaction of bracket/surfaces/quadrant was also found
to be significant (<0.003). CONCLUSION: The maximum adherence of microorganisms
was observed with the composite bracket material and the least adherence of
microorganisms was observed with the titanium bracket material. The adherence of
microorganisms is relatively more in the slot area, when compare to the tie wings
surface maximum adherence of microorganism is observed in the upper left quadrant
and least adherence of microorganism is observed in the lower right quadrant.
There is a significant difference in adherence of microorganisms to various types
of brackets and the surfaces included in the study. There is no significant
difference in the adherence of microorganism to the bracket surfaces in the four
quadrants included in the study.
PMID- 26435613
TI - Evaluation of Shear Bond Strength of Newer Bonding Systems on Superficial and
Deep Dentin.
AB - BACKGROUND: The purpose of this study was to compare the shear bond strength of
nanocomposite resin to superficial dentin and deep dentin using two different
dentin bonding systems. MATERIALS AND METHODS: All teeth were sectioned at
various levels (superficial dentin: Dentin within 0.5-1 mm of dentinoenamel
junction; deep dentin: Dentin within 0.5 mm of the highest pulp horn) using a
Carborundum Disc and embedded in acrylic block of specific size. Selected
specimens (60 premolar teeth) were grouped randomly into three groups, the groups
were differentiated into superficial dentin, deep dentin, and control group which
were further divided into sub Group A and Subgroup B containing 10 teeth each,
depending on the bonding agents used. In Subgroup A, Tetric N Bond, and in
Subgroup B Single Bond Universal were used. In the control group no bonding agent
was used. The specimens were thermocycled for 500 cycles between 5 degrees C and
55 degrees C water bath for 40 s. Finally, the specimens were subjected to shear
bond strength study under INSTRON machine (Universal Testing Machine). The
maximum shear bond strengths were noted at the time of fracture (de-bonding) of
the restorative material. Results were analyzed using ANOVA test, Bonferroni
test, and paired t-test. RESULTS: Bond strength values of fifth generation
bonding system (Tetric N Bond) showed higher mean shear bond strength compared to
seventh generation bonding system (Single Bond Universal). There was a
significant fall in bond strength values as one reaches deeper levels of dentin
from superficial to deep dentin. CONCLUSION: There was a significant difference
between the bond strength of fifth generation bonding system (Tetric N Bond) and
seventh generation bonding system (Single Bond Universal). Decrease in the bond
strength values is seen for the deeper level of dentin as compared to superficial
dentin.
PMID- 26435614
TI - Microhardness Properties of Mineral Trioxide Aggregate and Calcium-enriched
Mixture Cement Plugs at Different Setting Conditions.
AB - BACKGROUND: Providing an apical stop in open apex roots is one of the endodontic
challenges. The aim of present study was to compare the surface hardness of both
mineral trioxide aggregate (MTA) and calcium-enriched mixture (CEM) cement at
different setting situations. MATERIALS AND METHODS: A total of 40 freshly
extracted human teeth with a single root and normal apex and no obvious caries or
curvatures were selected. The teeth were sectioned horizontally from the cement
enamel junction and 2 mm above the apex. Standard technique was administered for
cleaning and shaping of the canals. Open apex root canal was prepared by using
Peso reamer. The prepared teeth were randomly divided into four groups in which
two groups were filled by MTA and the other groups were filled by CEM. White MTA
and CEM cement plugs were prepared and condensed up to the apical end. In two
groups, moistened paper point was placed in the canals and in the other group
dried paper points was used. Vickers test was done to evaluate the microhardness
and the collected data were analyzed by Kruskal-Wallis and three-way ANOVA tests
using SPSS software version 18 at a significant level of 0.05. RESULTS: The
highest and lowest surface hardness was observed in CEM group at dried condition
with 4 mm thickness indentation (145.10 +/- 7.60 kg/mm(2)) and moist MTA group
indented at 8 mm thickness (111.25 +/- 5.37 kg/mm(2)). However, no significant
difference was noticed (P > 0.05). CONCLUSION: Humidity condition might not
influence the microhardness properties of both MTA and CEM cement apical plugs at
different tested indentation thickness.
PMID- 26435615
TI - A Comparative Study of Three Types of Rapid Maxillary Expansion Devices in
Surgically Assisted Maxillary Expansion: A Finite Element Study.
AB - OBJECTIVES: The aim of this study was to analyze the displacement pattern and
stress distribution during surgically assisted rapid maxillary expansion (RME)
with three different types of RME devices by constructing a finite element model.
MATERIALS AND METHODS: A finite element model is constructed from the
computerized tomography scans. According to the type of RME device, 3 groups were
simulated on this mesh model. The experimental groups were as follows; Group I
(tooth borne appliance), Group II (bone borne appliance), and Group III (hybrid
appliance). A Le fort I osteotomy with bilateral pterygomaxillary disjunction and
midpalatal split osteotomy cuts were incorporated in all the groups. The
displacement pattern and stress distribution for each 1 mm of activation of
appliance up to 10 mm is noted and analyzed. The data were analyzed using
Student's t-test, Analysis of Variance and Duncan new multiple range test.
RESULTS: Tooth borne appliance has more rotational tendencies. The bone borne and
the hybrid appliance exhibited similar stress patterns for the dissipation of the
forces produced by RME appliances. The pivoting effect decreased with the hybrid
and the bone borne appliance and can be utilized in patient with hyper divergent
growth. CONCLUSION: The pivoting effect is least with the hybrid appliances.
PMID- 26435616
TI - Comparative Study of Probiotic Ice Cream and Probiotic Drink on Salivary
Streptococcus mutans Levels in 6-12 Years Age Group Children.
AB - BACKGROUND: Dental caries is one of the most common health problems in the world.
Probiotics are one the various preventive methods to reduce dental caries. The
aim of this study is to compare the effectiveness of probiotic ice cream and
drink on salivary Streptococcus mutans levels in children of 6-12 years age
group. MATERIALS AND METHODS: A three phase study was carried out in children (n
= 50) of 6-12 years age with zero decayed missing filled teeth (dmft)/DMFT. They
were randomly divided into two equal groups. Saliva samples were collected before
the consumptions of probiotic ice cream and probiotic drink. Colony count
obtained was recorded as baseline data. For both groups probiotic ice cream and
drink was given randomly for 7 days and a washout period of 90 days were given
and then the saliva samples were collected and colony counting was done. RESULTS:
Statistical analysis was performed using Student's paired t-test and multiple
comparisons by Tukey's honest significant difference test which showed, there is
a significant reduction in salivary S. mutans level in both groups after 7 days
period. However, after washout period only probiotic ice cream showed reduction
whereas drink did not. Also, there was no significant difference between
probiotic ice cream and drink. CONCLUSION: Probiotic organisms definitely have a
role in reducing the salivary S. mutans level and ice cream would be a better
choice than drink. However, the prolonged use of the agents and their effects on
caries is still to be determined.
PMID- 26435617
TI - Oral Health Status and Treatment Needs of Police Personnel in Mathura City.
AB - BACKGROUND: All men are born equal and are endowed by their creator with some
basic rights. As the military is to defend the country from external threats, so
is the police for maintenance of the internal peace of the community. The
irregular shifts in their work schedule lead to neglecting or skipping of their
regular diet and indulging into adverse habits. It is the responsibility of the
society to safeguard the health of their defenders. MATERIALS AND METHODS: A
cross-sectional study was carried out on 475 central reserve police personnels in
Mathura city. Consent was obtained from the concerned authorities and the
subjects were clinically examined using WHO 2013 "Oral Health Assessment Form."
RESULTS: This study revealed that 99.6% subjects were males, 62% subjects were of
21-35 years age group, mean dentition status was found to be 0.66 +/- 2.08 and,
most of the subjects needed prompt treatment including scaling. CONCLUSION:
Police personnels provide a unique opportunity to study a large population from
diverse geographic backgrounds. Prevention oriented health education lectures
should be delivered and possibly, should also form part of their training
curriculum.
PMID- 26435618
TI - Estimation of Specific Salivary Enzymatic Biomarkers in Individuals with
Gingivitis and Chronic Periodontitis: A Clinical and Biochemical Study.
AB - BACKGROUND: Host response to periodontal disease includes the release of
different enzymes from stromal, epithelial or inflammatory cells. The enzymes
which are produced from these cells are associated with cell injury and cell
death like: Aspartate aminotransferase (AST), Alanine aminotransferase (ALT),
Alkaline phosphatase (ALP) and Blood urea nitrogen (BUN). Normal enzymatic
activity of these enzymes is necessary for healthy functioning of gingiva and
periodontium. The aim of the study is to estimate the levels of enzymes AST, ALT,
ALP and BUN and to correlate the level of estimated enzymes with that of clinical
parameters in the saliva of Healthy subjects, Gingivitis patients and patients
with chronic periodontitis. METHODS: The study included a total of 40 male
subjects within the age group of 21 to 50 years, and examined the activity of
enzymes AST, ALT, ALP and BUN in saliva spectrophotometrically and compared their
values between healthy subjects, gingivitis and chronic periodontitis patients.
Clinical parameters like OHI - S (Oral hygiene index - Simplified, SBI (Sulcus
Bleeding Index), PPD (Probing Pocket Depth), CAL (Clinical Attachment Level), and
PI (Periodontal Index) were recorded. RESULTS: Obtained results showed
statistically significant increases of activity of AST, ALT, ALP, and BUN in
saliva from patients with periodontal disease (p<0.001) in relation to gingivitis
and control groups. There was also an increase in periodontal parameters with an
increase in salivary enzymes. CONCLUSION: The present study shows that the
salivary enzyme activity can be used as biomarkers to determine periodontal
tissue damage, which may be useful in diagnosis, prognosis and evaluation of post
therapy effects in periodontal disease.
PMID- 26435619
TI - Evaluation and Comparison of Intermaxillary Tooth Size Discrepancy among Class I,
Class II Division 1, and Class III Subjects Using Bolton's Analysis: An in vitro
Study.
AB - AIM: The aim of the present study was to evaluation and comparison of
intermaxillary tooth size discrepancy among Class I, Class II division 1, and
Class III subjects using Bolton's analysis. MATERIALS AND METHODS: The pre
treatment casts were selected from the records of patients attending the
Department of Orthodontics of Meenakshi Ammal Dental College, Chennai. The sample
consists of 180 pre-treatment casts with both sexes evenly distributed with 60
casts in each type of malocclusion, i.e., Class I, Class II div 1, and Class III
malocclusion. The sample was selected according to angles classification. All
patients were Indian nationals, between the age group of 12 to 20 years and
Bolton's analysis done on all the casts. RESULTS: Statistically no significant
difference in all types of malocclusion except anterior Bolton's discrepancy in
Class III. CONCLUSION: Mean Bolton's anterior ratio for angles Class III subjects
was significantly greater than for Class I and Class II subjects. When Bolton's
overall ratio was compared there was no statistically significant difference
among Class I, Class II div 1, and Class III malocclusions.
PMID- 26435620
TI - Occupational Stress, Salivary Cortisol, and Periodontal Disease: A Clinical and
Laboratory Study.
AB - BACKGROUND: Periodontitis is a multifactorial disease, commonly associated with
most of the lifestyle diseases. In the recent years, the association between
periodontitis with occupational stress has evolved in various studies in many
developed settings. This study aims at studying the prevalence of periodontal
disease and its relationship with job stress among industrial labor workers
covered under Employee's State Insurance Corporation Scheme. MATERIALS AND
METHODS: The study included 180 subjects who were informed about the research
goals, and also requested to sign consents. The questionnaire included parts from
the generic job stress questionnaire from the National Institute of Job Stress
and Health. Dental examinations based on community periodontal index protocol
were done using WHO probe. Participants with moderate to severe periodontitis
(score 3, 4) were informed about the salivary cortisol test. The saliva samples
were collected and transported to the lab. Data were entered in EPI info 3.1.1
and analyzed in SPSS 14. The Chi-square analysis was done to measure association,
and logistic regression analysis was done to identify the independent association
of job stress to periodontitis. RESULTS: The study shows that 48% of the
participants reported to have job stress, and 55% had periodontitis. The mean
salivary cortisol level was 3.42 ng/dl. The results also indicated a higher odds
of having low levels of salivary cortisol among those who reported job stress. Bi
variant regression analyses show the relationship of periodontitis with job
stress to be much higher on controlling for other risk factors. The odds of
having periodontitis in relation to positive job stress were 6 times higher than
those who did not have positive job stress. CONCLUSIONS: This study shows a high
prevalence of job stress related periodontitis among industrial workers in India.
This research recommends the health and labor ministry to improve access to
dental care especially in rural areas and include psychiatric units and oral
health care as a part of primary health care. The factories administration should
encourage recreation and retreat of the workers so as to reduce the level of
stress at work. The factory administrations were recommended to have counselors
to help their employees.
PMID- 26435621
TI - Management of Biomedical Waste: An Exploratory Study.
AB - BACKGROUND: Dental operatories pose a threat due to the high chances of infection
transmission both to the clinician and the patients. Hence, management of dental
waste becomes utmost importance not only for the health benefit of the dentist
himself, but also people who can come into contact with these wastes directly or
indirectly. The present study was conducted to find out the management of
biomedical waste in private dental practice among 3 districts of Karnataka.
MATERIALS AND METHODS: The study population included 186 private practitioners in
3 districts of Karnataka (Coorg, Mysore, Hassan), South India. A pre-tested self
administered questionnaire was distributed to assess the knowledge and practices
regarding dental waste management. Descriptive statistics was used to summarize
the results. RESULTS: Out of 186 study subjects, 71 (38%) were females and 115
(62%) were males. The maximum number of participants belonged to the age group of
28-33 years (29%). Undergraduate qualification was more (70%). 90 (48%)
participants had an experience of 0-5 years. Chi-square analysis showed a highly
significant association between participant who attended continuing dental
education (CDE) program and their practice of dental waste management.
CONCLUSION: Education with regards to waste management will help in enhancing
practices regarding the same. In order to fill this vacuum CDE programs have to
be conducted in pursuance to maintain health of the community.
PMID- 26435622
TI - Prevalence of Spaced and Non-Spaced Dentition and Occlusal Relationship of
Primary Dentition and its Relation to Malocclusion in School Children of
Davangere.
AB - BACKGROUND: The aim of the current study was carried to determine the relation of
spacing, closed dentition, and occlusal relation with malocclusion in the primary
dentition in children during deciduous dentition period among school children of
Davangere. MATERIALS AND METHODS: A total of 945 school children all having
deciduous teeth were included in the study. Informed consent for the child's
participation is taken from the school principal. The dentition was examined
under natural daylight, and the data was recorded. All the school children were
screened for spaced and non-spaced dentition, molar and canine relationship.
RESULTS: The results concluded that most of the children showed spaced dentition
(82.1%) when compared to non-spaced dentition (17.9%) with males shown more
spaced dentition than compared to females. Among all children examined for molar
and canine relation, flush terminal molar relation (65%) showed highest among all
molar relation followed by mesial step (31%) and distal step (4%), and Class I
canine relation (90%) was significant followed by Class II (6%) and Class III
canine relation (4%). No significant difference was seen between right and left
side. CONCLUSION: The study concludes that determining the malocclusion and its
correction at an early age helps in preventing a future complication in permanent
dentition since stable primary occlusion leads to ideal occlusion in permanent
dentition. Spacing, i.e., primate and physiologic space with the terminal molar
relation in primary dentition indicates proper alignment of the permanent
dentition.
PMID- 26435623
TI - Patient's Perceptions Regarding Orthodontic Needs and Satisfactory Level with the
Procedure.
AB - BACKGROUND: In order to keep the patients satisfied with Orthodontic treatment
and to address the growing concern among new orthodontic patients, this study was
undertaken to evaluate patient's perceptions of their orthodontic treatment needs
and the satisfactory level with the procedure. METHODOLOGY: This cross-sectional
study was conducted among a sample of 362 patients who had received orthodontic
treatment. Questionnaires included information factors that encouraged them to
take orthodontic treatment, painful experience of orthodontic therapy, and also
to know the effectiveness of the treatment. Student's t-test and ANOVA test were
used to analyze results at P = 0.05. RESULTS: Most of the participants faced
problems due to their dentition (60.2%), followed by mastication 23.6%. It was
found that most of the study subjects were motivated by orthodontist to receive
the treatment (29.7%). When the participants were asked about the complications
faced by them during the procedure and the most common answer was a longer
duration of the treatment (23.3%). Pain was also a common factor faced by the
participants (15.9%). Significant results were seen according to gender and age.
CONCLUSION: The study concluded that problems in the dentition were the main
factor to seek orthodontic treatment and most of the subjects were convinced by
the specialist to undergo orthodontic therapy. Many problems faced during the
treatment, but still majority gave a positive response to the treatment.
PMID- 26435624
TI - Assessment of Ethnicity in Indian Population using Tooth Crown Metric Dental
Traits.
AB - BACKGROUND: Tooth crown dimensions vary between different ethnic groups,
providing insights into the factors controlling human dental development. This
present study compares permanent mesiodistal (MD) and buccolingual crown
dimensions between four ethnic groups, highlighting patterns of tooth size
between these groups and considers the findings in relation to genetic and
environmental influences. MATERIALS AND METHODS: MD and buccolingual tooth crown
dimensions were recorded using digital vernier calipers on dental casts derived
from four different human population: Iranians, Hindus, Muslims, and Christians.
RESULTS: Obtained measurements were subjected to statistical analysis. The
Christian sample was found to have the largest teeth overall, whereas the Iranian
sample generally displayed the smallest MD and buccolingual crown dimensions (P <
0.001). Comparisons of coefficients of variation for teeth within each class
showed that the later-forming teeth displayed greater variation in MD size than
the earlier-forming teeth. CONCLUSION: The different patterns of tooth size
observed between the study samples are thought to reflect differences in the
relative contributions of genetic and environmental influences to dental
development between the four population. Using a standardized methodology,
significant differences in MD and buccolingual crown dimensions have been
demonstrated between four human ethnic groups. There were also distinct
differences in the patterns of crown size between the groups, with the later
forming teeth in each type generally showing greater size variation.
PMID- 26435625
TI - The Effect of Four Commonly used Root Canal Irrigants on the Removal of Smear
Layer: An In-vitro Scanning Electron Microscope Study.
AB - BACKGROUND: The objective of this study was to compare the efficiency of four
commonly used chemicals in their ability to remove smear layer after
instrumentation using scanning electron microscope (SEM). MATERIALS AND METHODS:
Seventy-five extracted single canaled teeth of roots ranging 10-12 mm in length
were used for the study. Teeth were divided into 4 study groups and 1 control
group of 15 teeth each. Standard access to the pulp chambers were performed with
diamond burs. The lengths of the teeth were determined by the introduction of a
size 15 K-file into the root canal until the tip reached the apical foramen. The
working length for preparation of the canal is set 0.5 mm shorter than the
measurement. Irrigation was performed using 2 ml of irrigant for every instrument
change and finally rinsed using 5 ml of the respective solutions. The roots were
then split with a chisel and hammer. One-half of each tooth was selected and
prepared for SEM examination. After assembly on coded stubs, the specimens were
placed in a vacuum chamber and sputter-coated with a 300 A gold layer. The
specimens were then analyzed using a Philips SEM XL 30. The dentinal wall of the
cervical, middle and apical thirds was observed at magnifications of up to *1000
for the presence/absence of smear layer and visualization of the entrance to
dentinal tubules. Photomicrographs (*1000) of these areas on each of the coronal,
middle and apical thirds were made Data were analyzed using Kruskal-Wallis test
and Mann-Whitney U test. RESULTS: SEM study done on these prepared teeth with the
popularly used four chemicals, namely, 3% NaOCl (Group A), 3% NaOCl followed by
17% ethylene diamine-tetra-acetic acid (Group B), 0.2% chlorhexidine (Group C)
and 3% NaOCl followed by MTAD (Group D), with distilled water (Group E) which is
used as control, revealed that NaOCl showed statistically significant, better
cleansing effect than distilled water. Chlorhexidine and NaOCl showed equal kind
of efficacy but were statistically significant, with lower efficacy than MTAD. It
may be concluded that MTAD appears to be the most effective solution compared to
the rest. CONCLUSION: The study demonstrated that MTAD as a final rinse after the
entire instrumentation with 3% NaOCl as irrigant provided the best cleansing in
all parts of the root canal system. The smear layer has been shown to hinder the
penetration of intracanal disinfectants and sealers into dentinal tubules and has
the potential of compromising the seal of the root filling. Degradation of the
smear layer after treatment may contribute to leakage and reinfection of the root
canal space. Removal of the smear layer reduced the penetration of bacteria
through the root canal system after root filling.
PMID- 26435626
TI - Anxiety and Depression in Facial Injuries: A Comparative Study.
AB - BACKGROUND: This study was performed to identify the presence of anxiety and
depression in patients who had sustained facial injuries; additionally we aimed
to identify other variables that may modify the psychological response to trauma
that include gender and age. MATERIALS AND METHODS: The participants were 153
patients from multimodal trauma centers in Bangalore city who sustained
disfiguring facial injuries were taken up. Of the 153 patients, 81 patients were
male (51 less than 50 years of age and 30 more than 50 years of age) and 72
patients were female (40 less than 50 years of age and 32 more than 50 years of
age) and 111 patients with non-disfiguring facial injuries out of which 54 were
male patients and 57 were female patients. The assessments were carried out at 3
time intervals (the date of discharge [DOD], 1-month post-operatively and 6
months post-operatively) of the follow-up. The hospital anxiety and depression
scale (HADS) was used to assess the anxiety and depression of the facial trauma
patients. RESULTS: Statistically significant higher means of HADS both for
anxiety and depression were present in patients with disfiguring facial injuries
compared to non-disfiguring facial injuries, female patients compared to male
patients after the 1-month and 6 months post-operatively, the mean anxiety and
depression scores of males and female patients were significantly higher for
those who aged less than 50 years compared to those who aged more than 50 years.
CONCLUSION: The results of this study led to the conclusion that in comparison
with patients who had facial disfiguring injuries and non-disfiguring facial
injuries, the mean HADS scores were significantly higher in the disfiguring
facial injury patient. This indicates increased Anxiety and Depression levels and
this was observed at all three study intervals (DOD, 1-month and 6 months post
operatively). The HADS was higher in female patients who were lesser than 50
years age compared to male patients of the same age group, which implies higher
anxiety and depression levels.
PMID- 26435627
TI - Revelation of Viral - Bacterial Interrelationship in Aggressive Periodontitis via
Polymerase Chain Reaction: A Microbiological Study.
AB - BACKGROUND: Periodontal disease is one of the most common and complex disease
affecting mankind. Being multifactorial in etiology it encompasses a variety of
infectious entities with various unique microbial constellations and immune
responses. A bacteriologic cause alone seems insufficient in explaining several
clinical features of the periodontal disease. Recent studies suggest that
periodontal herpes viruses comprise an important source of triggering periodontal
tissue destruction. The following study aims to assess human cytomegalovirus
(HCMV), Epstein-Barr virus (EBV-I) interaction with the established
periodontopathic bacteriae, Porphyromonas gingivalis (Pg) and Aggregatibacter
actinomycetemcomitans (Aa) in pathogenesis of aggressive periodontitis (AgP)
using Hotstart polymerase chain reaction (PCR). MATERIALS AND METHODS: A total of
30 subjects, 15 with AgP and 15 healthy controls contributed random subgingival
plaque samples. PCR methodology was used to identify the subgingival
herpesviruses, Pg, and Aa. Yates corrected Chi-square test was employed to
identify a statistical association between herpesviruses and periodontopathic
bacteriae. RESULTS: Findings suggested that viruses may be pertinent to disease
progression. The prevalence of the periodontopathic bacteria Aa was found in
53.33% (P = 0.0168, S) and Pg in 40% (P = 0.2155, NS) of the AgP patients.
Herpesviruses, HCMV and EBV-I were found to have a prevalence of 46.67% (P =
0.039, S) and 40% (P = 0.084, NS). The viral and bacterial co-infection was found
to be 77.78% (P = 0.0002, S) with Aa and HCMV. CONCLUSION: The present data
reveals, viruses may exert periodontopathic effect by causing local
immunosupression which may set a stage for the subgingival colonization and
multiplication of periodontal bacteriae. Further studies are needed to develop an
understanding into the significance of herpesviruses in human periodontitis
which, may allow for improved diagnosis, more specific therapy and ultimately
disease prevention.
PMID- 26435628
TI - Comparison of Frictional Forces Generated by a New Ceramic Bracket with the
Conventional Brackets using Unconventional and Conventional Ligation System and
the Self-ligating Brackets: An In Vitro Study.
AB - BACKGROUND: Fixed orthodontic mechanotherapy is associated with friction between
the bracket - wire - ligature interfaces during the sliding mechanics. A sound
knowledge of the various factors affecting the magnitude of friction is of
paramount importance. The present study was done to analyze and compare the
frictional forces generated by a new ceramic (Clarity Advanced) bracket with the
conventional, (metal and ceramic) brackets using unconventional and conventional
ligation system, and the self-ligating (metal and ceramic) brackets in the dry
condition. MATERIALS AND METHODS: The various bracket wire ligation combinations
were tested in dry condition. The brackets used were of 0.022" * 0.028" nominal
slot dimension of MBT prescription: Stainless steel (SS) self-ligating bracket
(SLB) of (SmartClip), SS Conventional bracket (CB) (Victory series), Ceramic SLB
(Clarity SL), Conventional Ceramic bracket with metal slot (Clarity Bracket),
Clarity Advanced Ceramic Brackets (Clarity(TM) ADVANCED, 3M Unitek). These
brackets were used with two types of elastomeric ligatures: Conventional
Elastomeric Ligatures (CEL) (Clear medium mini modules) and Unconventional
Elastomeric Ligatures (UEL) (Clear medium slide ligatures, Leone orthodontic
products). The aligning and the retraction wires were used, i.e., 0.014" nickel
titanium (NiTi) wires and 0.019" * 0.025" SS wires, respectively. A universal
strength testing machine was used to measure the friction produced between the
different bracket, archwires, and ligation combination. This was done with the
use of a custom-made jig being in position. RESULTS: Mean, standard deviation,
and range were computed for the frictional values obtained. Results were
subjected to statistical analysis through ANOVA. The frictional resistance
observed in the new Clarity Advanced bracket with a conventional elastomeric
ligature was almost similar with the Clarity metal slot bracket with a
conventional elastomeric ligature. When using the UEL, the Clarity Advanced
bracket produced lesser friction than the conventional metal bracket; but not
less than the ceramic metal slot bracket. Ceramic SLB produced lesser friction
when compared with the Clarity Advanced bracket with UEL, but the metal SLB
produced the least friction among all the groups and subgroups. CONCLUSION: The
present study concluded that the SS SLB produced least friction among all groups.
Using the archwire and ligation method, frictional forces observed in the Clarity
Advanced bracket and the conventional ceramic with metal slot bracket were almost
similar; but the least resistance was determined in SS CB using both the ligation
(CEL and UEL) system.
PMID- 26435629
TI - Stress Induced in Periodontal Ligament under Orthodontic Loading (Part II): A
Comparison of Linear Versus Non-Linear Fem Study.
AB - BACKGROUND: Simulation of periodontal ligament (PDL) using non-linear finite
element method (FEM) analysis gives better insight into understanding of the
biology of tooth movement. The stresses in the PDL were evaluated for intrusion
and lingual root torque using non-linear properties. MATERIALS AND METHODS: A
three-dimensional (3D) FEM model of the maxillary incisors was generated using
Solidworks modeling software. Stresses in the PDL were evaluated for intrusive
and lingual root torque movements by 3D FEM using ANSYS software. These stresses
were compared with linear and non-linear analyses. RESULTS: For intrusive and
lingual root torque movements, distribution of stress over the PDL was within the
range of optimal stress value as proposed by Lee, but was exceeding the force
system given by Proffit as optimum forces for orthodontic tooth movement with
linear properties. When same force load was applied in non-linear analysis,
stresses were more compared to linear analysis and were beyond the optimal stress
range as proposed by Lee for both intrusive and lingual root torque. To get the
same stress as linear analysis, iterations were done using non-linear properties
and the force level was reduced. CONCLUSION: This shows that the force level
required for non-linear analysis is lesser than that of linear analysis.
PMID- 26435630
TI - Association of Postmenopausal Osteoporosis and Periodontal Disease: A Double
Blind Case-Control Study.
AB - BACKGROUND: Both osteoporosis (OP) and periodontitis are chronic inflammatory
diseases associated with bone loss mediated by local and systemic factors. The
two diseases share common risk factors. Previous studies have suggested that OP
in itself is a predisposing factor for periodontal tissue destruction in
postmenopausal women. However, only a moderate correlation has been shown between
the two conditions. In this study, we compared the severity of periodontal
disease in postmenopausal osteoporotic women and postmenopausal women without OP.
MATERIALS AND METHODS: The study group consisted of 100 postmenopausal women in
the age group of 50-65 years: Group 1 (50 osteoporotic) and Group 2 (50 non
osteoporotic women). Periodontal parameters included sulcus bleeding index, oral
hygiene index simplified, probing pocket depth (PPD), and clinical attachment
loss (CAL), interproximal alveolar bone loss (ABL), and number of missing teeth.
The correlation of periodontal disease status with systemic bone mineral density
(BMD) was evaluated by dual-energy X-ray absorptiometry. RESULTS: The results
indicated that osteoporotic (Group 1) women had a significantly greater PPD, CAL,
and ABL when compared with the non-osteoporotic Group 2 (P < 0.0001). There was
no significant correlation between BMD and various parameters between the groups.
CONCLUSIONS: Within the limitations of the present study it was noted that
postmenopausal OP is associated with an increased incidence and severity of
periodontal disease. Educating postmenopausal osteoporotic women regarding the
importance of good oral care should be part of their management regime. Hence, it
could be inferred a possibility of a probable relationship between OP and
periodontal disease, but long-term prospective studies are warranted in the
future in order to provide definitive evidence.
PMID- 26435631
TI - Modified Esthetic Splint Design for Management of Multiple Traumatic Injuries in
Children: A Case Report.
AB - Traumatic injuries to the dento-alveolar structures are emergencies that
compromise the quality of life of the patients. In addition to symptomatic
management, definitive functional restoration and suitable rehabilitation becomes
a major treatment objective in such cases. The dynamics of the traumatic forces
may cause multiple injuries of different grades to the oral and para-oral
structures, which makes comprehensive management a greater challenge to the
dentist. The present case report elaborates a modified esthetic splint designed
to treat multiple dental injuries in children, which can promote healing, restore
optimal functionality along with esthetic rehabilitation to psychologically
benefit the child during the time of recovery.
PMID- 26435632
TI - Open Sinus Lift Surgery and the Importance of Preoperative Cone-Beam Computed
Tomography Scan: A Review.
AB - Open sinus lift surgery is a form of pre-prosthetic surgery for increasing the
quality and quantity of bone in the posterior region of the maxilla. Pre
operative assessment of the maxillary sinus is essential for the success of this
surgery. PubMed search was carried out in English language literature for open
sinus lift surgery and cone-beam computed tomography (CBCT). The results focused
on anatomic variants, vascular anatomy, complications, osteotomy/ostectomy window
dimensions and thickness of the Schneiderian Membrane. 59 articles were included
in this review. Features other than the height and the width of the residual
alveolar ridge that should be evaluated in preoperative CBCT scan include the
thickness of the lateral maxillary sinus wall, the presence of the alveolar
antral artery and its diameter, the maxillary sinus floor width and angulation,
irregularity of sinus floor, intimate relation of Schneiderian membrane with the
roots of the adjacent teeth, sinus septum, and the quality of subantral bone.
Other conditions that occasionally may be observed in special situations are also
explained. More than ten parameters should be checked in evaluating CBCT images
of paranasal sinuses other than the width and the length of the residual ridge in
the posterior region of the maxilla. Each of them may have a significant impact
on the results of the open sinus lift surgery.
PMID- 26435633
TI - Microdentistry with Lasers.
AB - Treating infants and young children is a rewarding experience, especially when we
guide parents and children down the path of prevention and interception of oral
disease. The pediatric dentist has to be updated about the new technologies to
treating patients along with basic principles. This article gives a brief
discussion on the types, applications, advantages, and limitations of the use of
lasers in pediatric dentistry.
PMID- 26435634
TI - Tissue Engineering: Step Ahead in Maxillofacial Reconstruction.
AB - Within the precedent decade, a new field of "tissue engineering" or "tissue
regeneration" emerge that offers an innovative and exhilarating substitute for
maxillofacial reconstruction. It offers a new option to supplement existing
treatment regimens for reconstruction/regeneration of the oral and craniofacial
complex, which includes the teeth, periodontium, bones, soft tissues (oral
mucosa, conjunctiva, skin), salivary glands, and the temporomandibular joint
(bone and cartilage), as well as blood vessels, muscles, tendons, and nerves.
Tissue engineering is based on harvesting the stem cells which are having
potential to form an organ. Harvested cells are then transferred into scaffolds
that are manufactured in a laboratory to resemble the structure of the desired
tissue to be replaced. This article reviews the principles of tissue engineering
and its various applications in oral and maxillofacial surgery.
PMID- 26435635
TI - Telescopic Partial Dentures-Concealed Technology.
AB - The ideal goal of good dentist is to restore the missing part of oral structure,
phonetics, his look and the most important is restored the normal health of the
patient, which is hampered due to less or insufficient intake of food. Removable
partial denture (RPD) treatment option is considered as a notion, which precludes
the inevitability of "floating plastic" in edentulous mouth, that many times fail
to fulfill the above essential of the patients. In modern dentistry, though the
dental implants or fixed partial denture is the better options, but they have
certain limitations. However, overdentures and particularly telescopic denture is
the overlooked technology in dentistry that would be a boon for such needy
patients. Telescopic denture is especially indicated in the distal edentulous
area with minimum two teeth bilaterally present with a good amount of periodontal
support. This treatment modality is sort of preventive prosthodontics remedy,
which in a conservative manner preserve the remaining teeth and helps in
conservation of alveolar bone ultimately. There are two tenets related to this
option, one is constant conservation edentulous ridge around the retained tooth
and the most important is the endless existence of periodontal sensory action
that directs and monitor gnathodynamic task. In this option the primary coping or
inner coping are cemented on the prepared tooth, and a similar removable outer or
inner telescopic crown placed tightly by using a mechanism of tenso-friction,
this is firmly attached to a removable RPD in place without moving or rocking of
the prosthesis, which is the common compliant of almost all patients of RPD.
Copings are also protecting the abutment from tooth decay and also offers
stabilization and maintaining of the outer crown. The outer crown engages the
inner coping and gives as an anchor for the remainder of the dentition. This work
is the review of telescopic prosthesis which is well supported by the case
discussion, and designates the utilization of favorable retained tooth/teeth as
abutment that drastically minimized alveolar bone resorption beneath the
prosthesis and give the maximum tactile sensation of natural teeth to the
patient, which is not possible with other type of RPD.
PMID- 26435636
TI - Pseudoepitheliomatous Hyperplasia in Oral Lesions: A Review.
AB - Pseudoepitheliomatous hyperplasia (PEH) is a histopathological reaction pattern
to various stimuli, which includes trauma, infection, inflammation, neoplasia. It
is seen as tongue like epithelial proliferation invading the connective tissue
and should not be mistaken for squamous cell carcinoma (SCC). This review enlists
oral lesions which exhibit PEH with a note on how to differentiate SCC from PEH.
PMID- 26435637
TI - Mesenchymal-Epithelial Transition in Oral Cancer.
PMID- 26435638
TI - Closed-Loop Multitarget Optimization for Discovery of New Emulsion Polymerization
Recipes.
AB - Self-optimization of chemical reactions enables faster optimization of reaction
conditions or discovery of molecules with required target properties. The
technology of self-optimization has been expanded to discovery of new process
recipes for manufacture of complex functional products. A new machine-learning
algorithm, specifically designed for multiobjective target optimization with an
explicit aim to minimize the number of "expensive" experiments, guides the
discovery process. This "black-box" approach assumes no a priori knowledge of
chemical system and hence particularly suited to rapid development of processes
to manufacture specialist low-volume, high-value products. The approach was
demonstrated in discovery of process recipes for a semibatch emulsion
copolymerization, targeting a specific particle size and full conversion.
PMID- 26435639
TI - Nesfatin-1 and its effects on different systems.
AB - Nesfatin-1 is a peptide secreted by peripheral tissues, central and peripheral
nervous system. It is involved in the regulation of energy homeostasis related
with food regulation and water intake. Nesfatin-1 can pass through the blood
brain barrier in both directions. It suppresses feeding independently from the
leptin pathway and increases insulin secretion from pancreatic beta islet cells.
That is why nesfatin-1 has drawn attention as a new therapeutic agent, especially
for the treatment of obesity and diabetes mellitus. Its effects on nutrition have
been studied in more detail in literature. On the other hand, its effects on
other physiological parameters and mechanisms of action still need to be
clarified. Synthesizing the research on nesfatin-1 can help us better understand
this field. Hippokratia 2015, 19 (1): 4-10.
PMID- 26435640
TI - Constipation in Childhood. An update on evaluation and management.
AB - OBJECTIVE: Constipation is a frequent problitalic in childhood and may be defined
as delay or difficulty in defecation that persists for longer than two weeks. It
is one of the ten most frequent pathological conditions that a general
paediatrician deals with. The aim of this review is to provide the general
paediatrician an overview of constipation in children discussing the etiology,
differential diagnosis, signs and symptoms and patient evaluation. METHODS: We
provide an overview on the pathogenesis, the diagnostic approach and the
managitalicent of constipation based on electronic literature searches using the
best available evidence from PubMed, Medline, Google Scholar, the European
Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and
the North American Society of Pediatric Gastroenterology, Hepatology and
Nutrition (NASPGHAN). RESULTS: The most common type of constipation is functional
accounting for 90-95% of all cases. In a small percentage of children, who may
have an organic cause of constipation, an appropriate laboratory investigation
and imagine studying is warranted. CONCLUSIONS: Functional constipation
ritalicains a frequent problitalic in childhood. Treatment options differ between
infants and children. italicphasis on recommended regimens for maintenance and
how to reduce medication will help to improve the long-term outcome. Moreover, it
is of great importance to follow constipated children closely and restart
medication promptly. On treatment failure or on suspicion of organic disease the
patient should be referred for further evaluation. Hippokratia 2015, 19 (1): 11
19.
PMID- 26435641
TI - Research on intraoperative iris behavior in rabbits treated with tamsulosin and
finasteride.
AB - AIM: The purpose of this study was to investigate intraoperative iris behavior
during some phacoemulsification maneuvers in rabbits treated with tamsulosin or
finasteride. MATERIAL AND METHOD: An experimental study was conducted on 26 Metis
male rabbits aged 1.5 - 2 years, body weight between 3.4 and 5.6 kg, divided into
three groups: Group 1 - Control, 6 rabbits; Group 2 - tamsulosin, 10 rabbits;
Group 3 - finasteride, 10 rabbits. Dose calculation was performed according to
body surface area ratio man/rabbit, taking into account the median lethal dose
LD50. Surgery study in rabbits was done over two days by the same specialist
using an adapted protocol. He was not informed before or during surgeries which
group the animal belonged to, the order being random with a quasi-uniform
distribution. Valid results for a modified iris behavior were obtained from two
steps of the procedure (cannula irrigation maneuver and irrigation-aspiration).
The iris billowing was graded from 0 to 3, according to severity. RESULTS: The
risk of intraoperative iris billowing was higher in rabbits included in
tamsulosin group [OR=8.33 (CI 95% 0.63-110.09)], but insignificant statistically
compare with control group (p= 0.13). In rabbits treated with finasteride the
risk of intraoperative iris billowing is increased compared with those without
treatment [OR=11.6 (CI 95% 0.92-147.6)], but insignificant statistically (p=
0.11). CONCLUSION: In our research, we showed an increased risk of intraoperative
iris billowing in rabbits treated with finasteride, almost similar with those
obtained in rabbits treated with tamsulosin. Further experimental or clinical
studies to confirm the role of finasteride in the etiology of intraoperative
floppy iris syndrome in humans are needed. Hippokratia 2015, 19 (1): 20-24.
PMID- 26435642
TI - Common VDR polymorphisms and idiopathic short stature in children from northern
Greece.
AB - BACKGROUND: A Vitamin D Receptor gene (VDR) polymorphism, rs10735810 (Fok1), has
been associated in the past with idiopathic short stature (ISS) in a linkage
study. We have investigated the association of the same, as well as a different
polymorphism in the same gene [rs731236 (Taq1)] with ISS, in an independent study
in Greek children. METHODS: The VDR rs10735810 (Fok1) and rs731236 (Taq1)
polymorphisms were genotyped in a group of ISS children (n= 47) and an age and
sex-matched group of normal height children (n= 60) from northern Greece.
Genotyping was accomplished through established PCR-RFLP methods. RESULTS: An
association trend of rs10735810 with ISS was observed, with the TT (ff) genotype
being apparently underrepresented among ISS children compared to controls (p=
0.076; OR= 0.165, 95% CI= 0.025-1.094). CONCLUSIONS: The above results, together
with recent evidence related to the functionality of the rs10735810 polymorphism,
cannot exclude an involvement of VDR in the pathogenesis of ISS. Hippokratia
2015, 19 (1): 25-29.
PMID- 26435643
TI - Validation of revised Epstein's criteria for insignificant prostate cancer
prediction in a Greek subpopulation.
AB - BACKGROUND: Different treatment options for patients with prostate cancer (PCa)
are applicable after stratifying patients according to various classification
criteria. The purpose of our study is to evaluate the revised Epstein's criteria
for insignificant PCa prediction in a Greek subpopulation. METHODS: During a 4
year-period, 172 Cretan patients were submitted to radical retropubic
prostatectomy in our institution. 23 out of them met the revised Epstein's
criteria for the presence of clinically insignificant PCa (clinical stage T1c,
prostate specific antigen density < 0.15 ng/ml/g, absence of Gleason pattern 4-5,
<3 positive biopsy cores, presence of <50% tumor per core) during pre-treatment
evaluation and were retrospectively included in the study. Post-surgery outcomes
were evaluated including pathological stage, surgical margins and Gleason score
upgrade. RESULTS: Organ confined disease and insignificant PCa were predicted
with a 74% and 31% accuracy, respectively. These figures are remarkably lower
than those derived from similar studies worldwide. CONCLUSIONS: Due to the high
variation in the revised Epstein's criteria prediction accuracy observed
worldwide, the development and implementation of novel tools/nomograms with a
greater predictive accuracy is still warranted. Hippokratia 2015, 19 (1): 30-33.
PMID- 26435644
TI - West Nile virus IgM and IgG antibodies three years post- infection.
AB - BACKGROUND: West Nile virus (WNV) causes to humans a variety of symptoms, from
asymptomatic infection to severe neuroinvasive disease. In a previous study, it
was shown that WNV IgM antibodies persisted in three of 26 (12%) patients, nine
months after onset of the symptoms. The aim of the present study was to test 10
of these patients, three years post-infection for probable persistence of IgM
antibodies and to investigate their IgG antibody patterns. MATERIAL AND METHODS:
In summer 2013 serum samples were collected from 10 persons who were infected
with WNV in 2010; 6 of them had a neuroinvasive disease. The three persons with
detectable WNV IgM antibodies, nine months after onset of the symptoms, were
included in the study. All samples were tested by ELISA in parallel with their
stored paired samples taken in 2011. The positive results were confirmed by
neutralization test. RESULTS: WNV IgM antibodies were still detectable in the
three persons, while high levels of WNV IgG and neutralizing antibodies were
present in nine of the 10 persons, regardless the involvement of the nervous
system. CONCLUSIONS: WNV IgM antibodies persist for more than three years in 12%
of patients with WNV infection, while WNV IgG antibodies persist and even
increase their levels, regardless the involvement of the nervous system,
suggesting that the immune response in the symptomatic WNV infections is strong
and long-lasting. Hippokratia 2015, 19 (1): 34-36.
PMID- 26435645
TI - Characteristics and outcome of patients with difficult weaning from mechanical
ventilation: an 18 years' experience of a respiratory intermediate unit attached
to a pulmonary department.
AB - BACKGROUND: Respiratory dysfunction often persists in post intensive care unit
(ICU) patients and intermediate care facilities have been established to ensure
the continuous of appropriate care. METHODS: The data of patients with difficult
weaning from mechanical ventilation admitted to a respiratory intermediate unit
(RIU) attached to a pulmonary department of a General Hospital, were
retrospectively analyzed. Clinical characteristics, weaning from mechanical
ventilation and tracheostomy, ICU readmission and RIU mortality were examined
over a period of 18 years (1993- 2010) that was randomly divided into three six
year-periods. RESULTS: A total of 548 patients (age 56.7+/-17.9 years) [mean +/-
standard deviation (SD)], of whom 80% with tracheostomy in place and 37.6% with
pressure ulcers, were examined. The ICU stay was 30.1+/-24.7 days (mean +/- SD)
and increased over time (p<0.05). Patients' baseline disorders were: chronic
respiratory disease (41.3%), chronic cardiovascular diseases (10.6%),
neuromuscular disease (22.8%) and miscellaneous (25.3%). The length of RIU stay
(22.8+/-19.5 days) was constant over the examined periods but an increase in age
and maintenance of tracheostomy were observed; 80% of patients were liberated
from mechanical ventilation and 58.5% from tracheostomy, whereas the RIU
mortality was 15%. CONCLUSION: In their vast majority patients with chronic
respiratory failure, who were admitted to RIU,were weaned from mechanical
ventilation, although in a substantial percentage the maintenance of tracheostomy
was mandatory after discharge. Hippokratia 2015, 19 (1): 37-40.
PMID- 26435646
TI - Urate crystals induce NLRP3 inflammasome-dependent IL-1beta secretion and
proliferation in isolated primary human T-cells.
AB - BACKGROUND: Urate through NOD-like receptor family, pyrin domain containing 3
(NLRP3) inflammasome-dependent caspase-1 activation stimulates macrophages to
secrete inteleukin-1beta (IL-1beta). Urate also enhances adaptive immunity
indirectly through its effect on antigen presenting cells. In this study, the
direct effect of urate on isolated primary human T-cells was evaluated. METHODS:
Isolated T-cells were cultured with or without monosodium urate crystals in the
presence or not of the NLRP3 inflammasome inhibitor glyburide. Activated cleaved
caspase-1 was assessed by means of western blotting, whereas caspase-1 activity
was measured colorimetrically in the cell lysates. IL-1beta was measured in the
supernatants by means of enzyme-linked immunosorbent assay. T-cell proliferation
was assessed by means of bromodeoxyuridine labelling and immunoenzymatic
detection. RESULTS: Urate induced caspase-1 activation and IL-1beta release by T
cells. It also induced proliferation of T-cells. Glyburide inhibited urate
induced caspase-1 activation, IL-1beta secretion and proliferation. CONCLUSIONS:
Urate, a well defined danger signal, stimulates directly human T-cells in a NLRP3
infmmasomela-dependent way. The subsequent IL-1beta secretion could enhance
inflammation, whereas expansion of T-cell clones could facilitate a subsequent
adaptive immune response. Hippokratia 2015, 19 (1): 41-46.
PMID- 26435647
TI - Use of lung clearance index to assess the response to intravenous treatment in
cystic fibrosis.
AB - BACKGROUND: Progressive lung disease is the main cause of clinical deterioration
and mortality in cystic fibrosis (CF) patients. Being able to assess the
effectiveness of interventions is very significant. OBJECTIVES: To assess the
response to intravenous (IV) treatment among CF patients, using forced expired
volume in 1(st) second (FEV1) and Lung Clearance Index (LCI) as outcome measures
and to compare the effect of IV treatment on lung function and LCI between CF
children being treated on a regular basis, or in case of a pulmonary
exacerbation. SUBJECTS AND METHODS: Thirty-two CF patients (15 males) with mean
age 9.90 (range: 2-23) years, performed spirometry and multiple breath washout
(MBW) before and one month after IV antibiotic treatment. Nineteen patients
received a course of elective treatment (group A) and 13 received IV antibiotic
regimens for an acute exacerbation (group B). RESULTS: Statistically significant
differences after treatment were seen in LCI (p<=0.001), and Forced Expiratory
Flow (FEF) z-scores (p<0.05). FEV1 did not change significantly after drug
intervention. Dividing patients into two groups, only LCI showed significant
change (p<0.05), when treatment was administered on a regular basis. Patients
being treated for an acute pulmonary exacerbation showed significant improvement
in most of the lung function parameters: LCI (p=0.0001), FEV1% (p=0.05), FEV1 z
score (p=0.033) and FEF25-75 (p=0.046). The mean LCI difference was significantly
greater in group B compared to group A (p=0.001). CONCLUSION: LCI is more
sensitive marker than FEV1 to assess the effect of IV antibiotic treatment among
CF children. IV antibiotics are more effective on lung function parameters, when
they are administered for an acute exacerbation, than when they are given on a
regular basis. Hippokratia 2015, 19 (1): 47-52.
PMID- 26435648
TI - Difference in efficacy of proton pump inhibitor between new-onset and recurrent
gastroesophageal reflux disease: Result from a study of on-demand versus
continuous maintenance therapy in Japan.
AB - BACKGROUND-OBJECTIVE: No study has focused on the difference in efficacy of
maintenance therapy between patients with new-onset and recurrent
gastroesophageal reflux disease (GERD). The aim of this study is to reveal this
point. METHODS: Endoscopically proven GERD patients who had completed 8-week
initial therapy were sequentially randomized to continuous arm (Omeprazole 20mg
od) or on-demand arm (Omeprazole 20mg on-demand). Patients filled in daily
symptoms and tablet usages for 24 weeks. Patients underwent upper GI endoscopy at
24 weeks. Symptom relief was defined as no symptoms for>6 days during a week. The
numbers of patients who achieved symptom relief and mucosal healing were compared
between the new-onset and recurrent groups in the continuous arm and in the on
demand arm, respectively. RESULTS: Among new-onset GERD [n=82 (continuous: 42
patients, on-demand: 40)], continuous arm achieved significant symptom-relief
than in on-demand arm at 4*,5*,6** and 17*week. Among recurrent GERD
[n=36(continuous: 17 patients, on-demand: 19)], continuous arm achieved
significant symptom-relief at 1**,2*,3*,4*,5**,7**,8**,17* and 18* week,
respectively (*<0.05,**<0.01). The number of healed patients was significantly
higher in new-onset group (60/68, 88.2%) than in recurrent group (17/30, 56.7%)
(<0.01). CONCLUSION: Since therapeutic response during maintenance therapy was
poor in recurrent GERD, continuous therapy is recommended in order to maintain
symptom-relief and mucosal healing. Hippokratia 2015, 19 (1): 53-56.
PMID- 26435649
TI - In vitro subminimum inhibitory concentrations of macrolide antibiotics induce
macrolide resistance in Mycoplasma pneumoniae.
AB - AIM: This study aims to investigate the inducing effect of subminimum inhibitory
concentrations of macrolide antibiotics on Mycoplasma pneumoniae (M. pneumoniae)
resistance to drugs. MATERIALS AND METHODS: One M. pneumoniae reference strain
M129 (ATCC 29342) and 104 clinical isolates were incubated at 37C for 6-8 days.
Genomic DNA of M. pneumoniae was extracted using TIANamp Bacteria DNA kit and
amplified by polymerase chain reaction (PCR). RESULTS: Ten sensitive isolates
obtained from 104 M. pneumoniae clinical isolates were induced by subminimum
inhibitory concentrations of macrolide antibiotics. Among them, three were found
to possess mutations in L4 and L22 ribosomal proteins. Two cases carried
simultaneously the C162A and A430G mutations of L4 and the T279C mutation of L22.
In addition, one case had only the A209T mutation of L4. CONCLUSIONS: Repeated in
vitro exposure to subminimum inhibitory concentrations of macrolide antibiotics
could induce selective mutations in ribosomal genes of M. pneumoniae clinical
isolates that cause resistance to macrolide antibiotics. Hippokratia 2015, 19
(1): 57-62.
PMID- 26435650
TI - Evaluation of children with juvenile idiopathic arthritis in southeastern Turkey:
a single center experience.
AB - BACKGROUND: The aim of this study was to investigate the disease characteristics
of children with juvenile idiopathic arthritis (JIA) in southeast Turkey.
METHODS: The International League of Associations for Rheumatology (ILAR)
criteria were used to diagnose JIA. Hospital records of the Pediatric
Rheumatology Unit, of the Dicle University Hospital, were reviewed
retrospectively and demographic, clinical and laboratory data were recorded.
RESULTS: Totally 213 children (103 boys, 110 girls), with an age range of 1.6-18
years were enrolled. The mean age of the disease onset was 8.1 years.
Polyarticular type was the most common (42.3%) presentation. The frequencies of
other JIA subtypes were as follows: oligoarticular 37.1%, systemic 8.9%,
enthesitis-related arthritis (ERA) 10.8% and psoriatic arthritis 0.9%. The knees
(74.2%) and ankles (54.0%) were the most commonly affected joints. Uveitis was
found in 4.2% of patients. Anti-nuclear antibodies were positive in 11.7% and HLA
B27 in 2.8% of patients. Active disease was seen in 57 (26.7%) patients at the
last visit. CONCLUSION: In the present study, polyarticular JIA was the
predominant subtype and there were fewer patients with positive ANA or uveitis
compared to previous studies. Hippokratia 2015, 19 (1): 63-68.
PMID- 26435651
TI - The role of gasless laparoscopy in differential diagnosis of acute abdomen.
AB - BACKGROUND: The diagnosis of acute abdomen in the emergency setting, still
remains a challenging problem. In these cases timely diagnosis and management is
of great importance, while the anesthetic risk is high. The combination of the
risk of an open laparotomy and the relative high likelihood of negative findings
when performed, creates the need for a better approach. The alternative actually
exists since 1911 when Eruheim made the first gasless laparoscopy. The aim of
this study is to put back into the spotlight, gasless laparoscopy in the
differential diagnosis of acute abdomen and to underline the advantages of this
simple, cheap and very useful technique, especially in patients that require
prompt diagnosis and have relative or absolute contraindications to general
anesthesia or pneumoperitoneum. METHODS: This study included 49 patients that
were managed with gasless laparoscopy for the diagnosis of acute abdomen, from
2011 to 2013. Two techniques were used: the mechanical lift of the anterior
abdominal wall and the LapVision device. RESULTS: From the 49 patients included
in the study, 41 were diagnosed with gasless laparoscopy while in eight the
results were uncertain or there wasn't any pathology involved. With both
techniques used, sample of the intraperitoneal fluid or biopsy could be obtained.
CONCLUSION: The gasless technique for laparoscopy is an extremely useful mean of
diagnosis in emergency conditions, or for patients with contraindications to
undergo laparoscopy by pneumoperitoneum. Requiring only local or regional
anesthesia, this technique could easily find application in diagnosis and
treatment, while avoiding unnecessary laparotomies. Hippokratia 2015, 19 (1): 69
72.
PMID- 26435652
TI - Surgical management of gastrointestinal stromal tumors: a single centre's
experience.
AB - BACKGROUND: Gastrointestinal stromal tumors (GISTs) represent 85% of all
mesenchymal neoplasms that affect the gastrointestinal track. Aim of this study
is to report a case series of 18 GISTs treated surgically in a single centre and
to discuss the diagnostic and therapeutic issues regarding these tumors. CASE
SERIES: A retrospective search of the unit's medical records from 2002 to 2014
was carried out, to collect all cases diagnosed and treated for GISTs.
Demographics and clinical features was obtained for all relevant cases. RESULTS:
Eighteen cases (18) of GIST were identified. Eleven tumors were located in the
stomach, 3 tumors in the duodenum and 4 tumors in the jejunum. The mean age at
diagnosis was 62.5 (range 42-81) years, while the male to female ratio was 1.57/1
(11 males/7 females). Patients presented with a variety of symptoms and all
underwent surgery. The 5-year-survival rate of these patients was 50%.
CONCLUSION: Due to non-specific presentation of GISTs, initial diagnosis of these
tumors may be delayed. High clinical suspicion and knowledge of their
characteristics are essentials in order to achieve an early diagnosis and lead
patients to surgery as soon as possible. Hippokratia 2015, 19 (1): 73-75.
PMID- 26435653
TI - Symptomatic cervical perineural (Tarlov) cyst: a case report.
AB - BACKGROUND: Perineural (Tarlov) cysts are benign, usually asymptomatic,
cerebrospinal fluid filled cysts of the spine, most often found in the sacral
region. DESCRIPTION OF CASE: We report a Tarlov cyst, located in the cervical
spine, in a 44-year-old woman who presented with a 3-week history of radicular
symptoms of the right C6 root. The perineural cyst was identified at the C5-C6
level following magnetic resonance imaging of the cervical spine. A conservative
approach was chosen, with the use of a soft cervical collar for two weeks, a 15
day-course of oral non-steroidal anti-inflammatory medication and instructions
concerning limitation of her activities. The outcome of this approach was 90%
improvement of her symptoms 24 months after her diagnosis. CONCLUSION: This is
the first report of a cervical Tarlov cyst treated conservatively without the use
of oral or injected steroids. The perineural cyst should be included in the
differential diagnosis of patients presenting with radicular symptoms.
Hippokratia 2015, 19 (1): 76-77.
PMID- 26435654
TI - Hypercalcemia and multiple osteolytic lesions in an adult patient with relapsed
pre-B acute lymphoblastic leukemia: a case report.
AB - BACKGROUND: Hypercalcemia and severe osteolytic lesions are rare complications of
acute lymphoblastic leukemia (ALL) in childhood, and those cases share similar
clinical features. Similarly, hypercalcemia is a rare feature in adult ALL. Here,
we report an uncommon case of an adult patient with relapsed precursor B ALL (pre
B ALL) who developed multiple osteolytic lesions and hypercalcemia. CASE
DESCRIPTION: A 24-year-old male patient, diagnosed with pre-B ALL, was admitted
in our hospital due to severe lumbar pain. After reviewing laboratory,
radiological and clinical findings, the patient was diagnosed as having relapse
of a mixed phenotype acute leukemia, according to bone marrow aspiration (9%
blasts) and cytogenetic analysis, with multiple osteolytic lesions in all lumbar
vertebrae, sacrum and ilium and severe hypercalcemia (13.3 mg/dL). Thus, FLAG-IDA
rescue therapy and hydration plus furosemide, corticoids and bisphosphonates were
administered. Despite initial amelioration, his hematological condition
deteriorated and he died due to severe sepsis as a result of severe
immunosuppression. CONCLUSION: Two possible mechanisms have been suggested for
hypercalcemia in hematological malignancy, either the leukemic infiltration or
the paraneoplastic production of a variety of humoral factors and proinflammatory
cytokines. However, hypercalcemia and severe osteolytic lesions are rare features
in ALL adult patients and their combination may be indicator of poor prognosis.
Hippokratia 2015, 19 (1): 78-81.
PMID- 26435655
TI - Ewing's sarcoma of the proximal phalanx of the foot: A rare case report.
AB - BACKGROUND: Ewing's sarcoma localized to foot is extremely rare. Local control is
mandatory because of the aggressive nature of the tumor. Therapeutic options for
these local tumors include neoadjuvant chemotherapy followed by surgery.
DESCRIPTION OF THE CASE: A 17-year-old female patient presented with a 6-month
history of progressive swelling and intermittent pain of the left great toe.
Plain radiography and magnetic resonance imaging revealed an expansile mass that
had originated from the proximal phalanx of the great toe and was destructing and
surrounding the distal phalanx. Her erythrocyte sedimentation rate and serum
lactate dehydrogenase levels were slightly elevated. Distant metastasis was not
detected. The patient underwent an open biopsy, which confirmed the diagnosis of
Ewing's sarcoma. She was treated with neoadjuvant chemotherapy and
disarticulation above the metatarsophalangeal joint. She received adjuvant
chemotherapy following the operation. The patient died 50 months after the
operation as a result of disseminated disease. CONCLUSION: The distal phalanx of
the foot is an extremely rare site for the development of Ewing's sarcoma. As
local control is important to avoid dissemination of the disease, neoadjuvant
chemotherapy followed by amputation or disarticulation of the affected digit and
subsequently adjuvant chemotherapy may be favorable modality for increasing the
patient's duration of survival. Hippokratia 2015, 19 (1): 82-84.
PMID- 26435656
TI - Anaplastic thyroid carcinoma presenting with gastric metastasis: a case report.
AB - INTRODUCTION: Anaplastic thyroid carcinoma (ATC) has the most aggressive
progression among thyroid malignancies. Most of the patients have metastasis,
especially to the lungs, liver and regional lymph nodes, at the time of
diagnosis. Gastrointestinal tract metastasis of ATC has been rarely reported. We
report a case who presented with gastrointestinal bleeding and was diagnosed with
ATC accompanied with gastric, skin, lung and adrenal gland metastases. CASE
REPORT: A 72-year-old male patient presented with one month history of neck mass,
weight loss and weakness and three-day-history of melena. On examination his
thyroid gland was tender on palpation and hyperplasic, multiple, painful, solid,
and fixed nodules were palpated.Ultrasonographic neck examination demonstrated an
enlarged thyroid gland and multiple hypoechoic nodules including cystic
degenerative areas; the largest 28 x 23 mm in size. Thyroid fine needle
aspiration biopsy was performed and biopsy results indicated ATC. Gastroscopy,
performed due to the gastrointestinal bleeding, detected a 4 x 6 mm polypoid
lesion on sternal pili of the gastric cardia and histopathological examination of
its biopsy demonstrated metastasis of ATC. CONCLUSION: We reported a case of ATC
with gastric, skin, lung and adrenal gland metastases, initially presenting with
gastrointestinal bleeding due to the gastric metastasis. Hippokratia 2015, 19
(1): 85-87.
PMID- 26435657
TI - Synchronous adenocarcinoma and echinococcosis in the same ovary: a rare clinical
entity.
AB - BACKGROUND: Serous adenocarcinoma is the most common subtype of ovarian
carcinoma, while ovarian echinococcosis is a rare disease of the female genital
system. The simultaneous presence of adenocarcinoma and echinococcosis in the
same ovary is extremely rare and little data exist regarding diagnosis and
treatment approach. MATERIALS AND METHODS: In the present paper, we report a rare
case of a 66-year-old Greek Caucasian woman of rural origin, with an adnexal
mass, ascitic and pleural fluid. The patient underwent exploratory laparotomy
following neoadjuvant chemotherapy, based on positive for malignancy pleural and
ascitic fluid cytology results. RESULTS: Histological examination of the surgical
specimen indicated the synchronous presence of echinococcosis and adenocarcinoma
in the same ovary. CONCLUSIONS: Ovarian hydatid cyst is extremely rare, but
should be suspected in patients with echinococcosis in other organs and those
coming from endemic areas. Moreover, the disease could mimic ovarian cancer, as
there are no specific symptoms and clinical signs. The coexistence of these two
diseases in the same ovary, although rare, is possible. It seems that the
presence of the hydatid cyst does not change the treatment approach of the
malignancy so that surgery with neoadjuvant or adjuvant chemotherapy, according
to the present guidelines, should be administered. Hippokratia 2015, 19 (1): 89
91.
PMID- 26435658
TI - Paraproteinemia and central retinal vein occlusion.
PMID- 26435659
TI - Post Kala Azar dermal leishmaniasis in a 15-month-old Greek boy.
PMID- 26435660
TI - Sevoflurane induction of anesthesia for a large epiglottic cyst removal when
awake intubation is not an option.
PMID- 26435661
TI - A rare case of left inferior vena cava with azygous continuation and presence of
the suprarenal segment of a right inferior vena cava.
PMID- 26435662
TI - Urgent bedside appendectomy for drain site evisceration.
PMID- 26435663
TI - Stickhandling my way to an unexpected career in academic paediatrics and
research.
PMID- 26435664
TI - Case 1: Cholestatic jaundice in an infant with Down syndrome.
PMID- 26435665
TI - Case 2: Acute paralysis in a 10-year-old girl.
PMID- 26435666
TI - Caring for children, focusing on children.
AB - Two First Nations girls with leukemia received a significant amount of media
attention in 2014 and 2015. In both cases, the parents refused to continue
chemotherapy, the only proven effective treatment; they opted instead for a
combination of traditional Aboriginal healing approaches and alternative
therapies offered in a facility outside of the country. One child has died; the
other relapsed and required chemotherapy to avoid death. Media reports were
polarized, focusing either on the historical legacy of distrust felt by First
Nations people when accessing health care, or the need for child protection
services to intervene. One article in the Canadian Medical Association Journal
focused on the legacy of mistrust and methods of countering it, but did not
address the legal and ethical duties of physicians in such situations. The
present commentary describes the events, responsibilities of professionals
involved and a course of action for physicians when faced with similar
circumstances.
PMID- 26435667
TI - Administration of inhaled gases at a temperature of 33.5 degrees C versus 37
degrees C for ventilated asphyxiated newborns undergoing therapeutic hypothermia.
PMID- 26435668
TI - Using simplified blood pressure tables to avoid underdiagnosing childhood
hypertension.
AB - BACKGROUND: Recent studies have revealed that hypertension remains underdiagnosed
in a significant number of children despite their recorded office blood pressure
(OBP) exceeding the recommended fourth report OBP thresholds. Simplified OBP
thresholds have been proposed to reduce this underdiagnosis of hypertension in
children. In clinical practice, OBP screened as elevated according to the fourth
report OBP thresholds are referred for ambulatory blood pressure (ABP) monitoring
to rule out 'white coat' hypertension. OBJECTIVES: The present study tested the
usefulness of simplified OBP thresholds to screen abnormal OBP for ABP monitoring
referral. METHODS: A total of 155 subjects were retrospectively analyzed with
paired OBP and ABP recordings obtained from an outpatient referral clinic. OBP
recordings were classified as abnormal according to the simplified and fourth
report OBP thresholds. ABP measurements were classified as abnormal according to
the ABP reference tables. RESULTS: Simplified blood pressure (BP) tables
correctly identified all OBP classified as abnormal according to fourth report BP
thresholds (kappa [kappa] 0.72 [95% CI 0.61 to 0.83]) for systolic OBP; kappa
0.92 [95% CI 0.86 to 0.99] for diastolic OBP). OBP classified as abnormal by the
simplified BP thresholds and by the fourth report BP thresholds performed
similarly for correctly identifying abnormal ABP measurements as per ABP
references (overlapping 95% CIs of the sensitivity, specificity and predictive
values and likelihood ratios). CONCLUSIONS: Simplified BP tables, proposed to
reduce the underdiagnosis of hypertension in children, can serve as a useful
screening tool to decide a referral for ABP monitoring. Future prospective
studies are needed to establish these findings.
PMID- 26435670
TI - Interventions for congenital talipes equinovarus (clubfoot).
PMID- 26435669
TI - Risk factors, practice variation and hematological outcomes of children
identified with non-anemic iron deficiency following screening in primary care
setting.
AB - OBJECTIVES: To determine the prevalence, risk factors, physician practice
patterns and longitudinal hematological outcome of children following screening
for non-anemic iron deficiency (NAID). METHODS: The present analysis was a
longitudinal cohort study invovling healthy children one to five years of age.
Descriptive statistics were used to describe the prevalence, risk factors,
practice patterns and hematological outcome of children identified with NAID. The
association between NAID and potential risk factors were examined using
multivariate logistic regression analysis. RESULTS: Of 2276 children undergoing
screening, 155 had NAID, corresponding to a prevalence of 7% (95% CI 5.95% to
8.05%). Risk factors significantly associated with NAID included: younger age (OR
1.08 [95% CI 1.06 to 1.11]), higher body mass index z-score (OR 1.22 [95% CI 1.01
to 1.48]), longer duration of breastfeeding (OR 1.05 [95% CI 1.01 to 1.08]) and
increased volume of cow's milk intake (OR 1.13 [95% CI 1.01 to 1.26]). An
assessment of practice patterns revealed that for 37% of children, an
intervention for NAID was documented; and for 8.4% a physician-ordered follow-up
laboratory test was completed to re-evaluate iron status. A total of 58 (37%)
children underwent a follow-up laboratory test, of whom 38 (65.5%) had resolution
of NAID, 15 (25.9%) had persistence of NAID and two (3.4%) had progression of
NAID to anemia. CONCLUSION: NAID is common in early childhood and is associated
with modifiable risk factors. Substantial practice variation exists in the
management of NAID. Further research is necessary to understand the benefits of
screening for NAID and evidence-informed practice guidelines may reduce practice
variation in the management of NAID in early childhood.
PMID- 26435671
TI - Acute flaccid paralysis surveillance: The need for ruling out polio infection.
PMID- 26435672
TI - Newborn male circumcision.
AB - The circumcision of newborn males in Canada has become a less frequent practice
over the past few decades. This change has been significantly influenced by past
recommendations from the Canadian Paediatric Society and the American Academy of
Pediatrics, who both affirmed that the procedure was not medically indicated.
Recent evidence suggesting the potential benefit of circumcision in preventing
urinary tract infection and some sexually transmitted infections, including HIV,
has prompted the Canadian Paediatric Society to review the current medical
literature in this regard. While there may be a benefit for some boys in high
risk populations and circumstances where the procedure could be considered for
disease reduction or treatment, the Canadian Paediatric Society does not
recommend the routine circumcision of every newborn male.
PMID- 26435674
TI - Corrigendum.
AB - [This corrects the article on p. 237 in vol. 20, PMID: 26175558.].
PMID- 26435673
TI - Preventing hospitalizations for respiratory syncytial virus infection.
AB - Respiratory syncytial virus infection is the leading cause of lower respiratory
tract infections in young children. Palivizumab has minimal impact on RSV
hospitilization rates as it is only practical to offer it to the highest risk
groups. The present statement reviews the published literature and provides
updated recommendations regarding palivizumab use in children in Canada.
PMID- 26435675
TI - Accuracy of a new clean-catch technique for diagnosis of urinary tract infection
in infants younger than 90 days of age.
AB - OBJECTIVE: To evaluate the accuracy of diagnosing urinary tract infections using
a new, recently described, standardized clean-catch collection technique.
METHODS: Cross-sectional study of infants <90 days old admitted due to fever
without a source, with two matched samples of urine obtained using two different
methods: clean-catch standardized stimulation technique and bladder
catheterization. RESULTS: Sixty paired urine cultures were obtained. The median
age was 44-days-old. Seventeen percent were male infants. Clean-catch technique
sensitivity was 97% (95% CI 82% to 100%) and specificity was 89% (95% CI 65% to
98%). The contamination rate of clean-catch samples was lower (5%) than the
contamination rate of catheter specimens (8%). CONCLUSIONS: The sensitivity and
specificity of urine cultures obtained using the clean-catch method through the
new technique were accurate and the contamination rate was low. These results
suggest that this technique is a valuable, alternative method for urinary tract
infection diagnosis.
PMID- 26435676
TI - Cognitive and motor function of neurologically impaired extremely low birth
weight children.
AB - BACKGROUND: Rates of neurological impairment among extremely low birth weight
children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is
unexamined. OBJECTIVE: To compare motor and cognitive functioning of ELBW
children with neurological impairment, including cerebral palsy and severe
hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005
(n=34). METHODS: Measures of function at 20 months corrected age included the
Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant
Development and the Gross Motor Functional Classification System as primary
outcomes and individual motor function items as secondary outcomes. RESULTS:
Analysis failed to reveal significant differences for the primary outcomes,
although during 2000 to 2005, sitting significantly improved in children with
neurological impairment (P=0.003). CONCLUSION: Decreases in rates of neurological
impairment among ELBW children have been accompanied by a suggestion of improved
motor function, although cognitive function has not changed.
PMID- 26435679
TI - OXIDATIVE STRESS IN HUMAN LEUKEMIA (HL-60), HUMAN LIVER CARCINOMA (HepG2), AND
HUMAN (JURKAT-T) CELLS EXPOSED TO ARSENIC TRIOXIDE.
AB - Recent studies have shown that arsenic trioxide can induce a clinical remission
in patients with acute promyelocytic leukemia. However, the molecular mechanisms
of action remain to be elucidated. In this research, we performed the MTT assay
to evaluate the cytotoxic effects of arsenic trioxide (ATO) to HL-60 cells and to
compare their relative sensitivity to that of HepG2, and Jurkat T cells. We also
performed the thiobarbituric acid test to determine the levels of malondialdehyde
(MDA) plus 4-hydroxy-2 (E)-nonenal (4-HAE) production in these three cell lines
following exposure to arsenic trioxide. The result of MTT assay clearly
demonstrated that ATO has a significant cytotoxic effect on HL-60, Jurkat, and
HepG2 cells; showing 24 hrs LD50 values of 6.4 +/- 0.6 MUg/mL, 15 +/- 3.84
MUg/mL, and 23.2 +/- 6.03 MUg/mL, respectively. These data indicated that HL-60
cells are about twice as sensitive to arsenic toxicity compared to Jurkat T cells
and about 3 times more sensitive to arsenic trioxide compared to HepG2 cells. The
result of the thiobarbituric acid test demonstrated that arsenic trioxide
treatment resulted in a significant increase (p <0.05) of MDA and HAE production,
indicating that oxidative stress plays a key role in arsenic induced toxicity and
cell injury. MDA and HAE levels were significantly higher in arsenic trioxide
treated HL-60 cells, indicating that these cells appear to be more sensitive to
oxidative stress than HepG2 and Jurkat T- cells. In summary, these results
indicate that the pharmacology of ATO as an effective anti-cancer drug is
associated with its cytotoxic effects in human promyelocytic leukemic cells. This
cytotoxicity is found to be mediated by oxidative stress, a biomarker of cellular
injury.
PMID- 26435680
TI - Population doubling level-dependent change of secreted glycosaminoglycan in
equine bone marrow-derived mesenchymal stem cells.
AB - In regenerative medicine using transplantation of mesenchymal stem cells (MSCs),
the importance of regulating the quality of MSCs has been well recognized;
however, there is little information concerning the relationship between the
population doubling level (PDL) and the stemness of MSCs in equine medicine. In
this study, we showed that the amount of glycosaminoglycan (GAG) secreted by bone
marrow-derived MSCs (BMSCs) decreases with increase of PDL. Enzymatic digestion
and two-dimensional electrophoresis revealed that a main component of GAG
produced by BMSCs was hyaluronan with a small amount of chondroitin sulfate.
Increase of PDL downregulated the expression of MSC CD markers, including CD44,
CD73, CD90, CD105, and CD146, along with loss of differentiation capacity. Thus,
the effect of hyaluronan supplement to the growth medium on both expression of CD
markers and the tri-lineage potential of BMSCs was evaluated. Expression of CD73
and CD90 was preserved by continuous addition of hyaluronan to the growth medium,
whereas mRNA levels corresponding to CD44, CD105 and CD146 were not preserved by
supplementation of hyaluronan. BMSCs subcultured with hyaluronan-supplemented
growth medium to PDL-12 showed osteogenic capacity, however adipogenic and
chondrogenic activities at PDL-12 were not preserved by exogenous hyaluronan.
These results suggest that downregulation of CD44, CD105 and CD146 might not
affect the osteogenic capacity. Taken together, the results suggested that
supplementation of hyaluronan to the growth medium might be effective at
maintaining the osteogenic capacity of equine BMSCs.
PMID- 26435681
TI - Experimental investigation of bone mineral density in Thoroughbreds using
quantitative computed tomography.
AB - Bone mineral density (BMD) is one of the indications of the strength and health.
BMD measured by quantitative computed tomography (QCT) was compared with that
measured by dual energy X-ray absorptiometry (DXA) and radiographic bone aluminum
equivalence (RBAE). Limbs were removed from horses that had been euthanized for
reasons not associated with this study. Sixteen limbs (left and right metacarpals
and metatarsals) from 4 horses were used to compare BMD as measured by QCT with
those measured by DXA and RBAE. There was a strong correlation between BMD values
measured by QCT and those measured by DXA (R(2)=0.85); correlation was also
observed between values obtained by QCT and those obtained by RBAE (R(2)=0.61).
To investigate changes in BMD with age, 37 right metacarpal bones, including 7
from horses euthanized because of fracture were examined by QCT. The BMD value of
samples from horses dramatically increased until 2 years of age and then
plateaued, a pattern similar to the growth curve. The BMD values of bone samples
from horses euthanized because of fracture were within the population range, and
samples of morbid fracture were not included. The relationship between BMD and
age provides a reference for further quantitative studies of bone development and
remodeling. Quantitative measurement of BMD using QCT may have great potential
for the evaluation of bone biology for breeding and rearing management.
PMID- 26435682
TI - Presumed monozygotic twins develop following transfer of an in vitro-produced
equine embryo.
AB - An equine embryo produced by intracytoplasmic sperm injection (ICSI) was trans
cervically transferred to a recipient mare and pregnancy was confirmed via
ultrasound examination on days 11, 12 and 15. On days 20 and 22, a single
embryonic proper with a heartbeat was observed. On day 29, two embryos proper
appeared during ultrasound examination, each possessing a heartbeat. Subsequent
examinations on days 35 and 39 revealed continued viability and development of
both embryos proper. On day 49, demise of both fetuses was present. Although no
DNA analysis or post-partum examinations were performed, it is presumed that the
fetuses were monozygotic twins based on membrane classification by ultrasound
imaging as well as development occurring after the transfer of a single in vitro
produced embryo.
PMID- 26435683
TI - Methicillin-resistant Staphylococcus aureus ulcerative keratitis in a
Thoroughbred racehorse.
AB - We report the first case of methicillin-resistant Staphylococcus aureus (MRSA)
keratitis in a racehorse. A 5-year-old mare developed punctate keratitis after
racing. The corneal ulcer continued to expand despite ophthalmic antimicrobial
therapy. On day 6, a conjunctival graft surgery was performed. The mare was
euthanized, following colitis and laminitis development on day 10. MRSA was
isolated from the corneal swab taken at the time of euthanasia.
Immunohistochemical analysis demonstrated gram-positive and anti-S. aureus
monoclonal antibody-positive cocci infiltration of the corneal stroma; and a
diagnosis of MRSA ulcerative keratitis was made. An ophthalmic antimicrobial
against the isolated MRSA did not improve the ocular lesion. The MRSA strain was
found to be staphylococcal cassette chromosome mec type II, a strain frequently
isolated from humans in Japan.
PMID- 26435684
TI - Improving spatial nitrogen dioxide prediction using diffusion tubes: A case study
in West Central Scotland.
AB - It has been well documented that air pollution adversely affects health, and
epidemiological pollution-health studies utilise pollution data from automatic
monitors. However, these automatic monitors are small in number and hence
spatially sparse, which does not allow an accurate representation of the spatial
variation in pollution concentrations required for these epidemiological health
studies. Nitrogen dioxide (NO2) diffusion tubes are also used to measure
concentrations, and due to their lower cost compared to automatic monitors are
much more prevalent. However, even combining both data sets still does not
provide sufficient spatial coverage of NO2 for epidemiological studies, and
modelled concentrations on a regular grid from atmospheric dispersion models are
also available. This paper proposes the first modelling approach to using all
three sources of NO2 data to make fine scale spatial predictions for use in
epidemiological health studies. We propose a geostatistical fusion model that
regresses combined NO2 concentrations from both automatic monitors and diffusion
tubes against modelled NO2 concentrations from an atmospheric dispersion model in
order to predict fine scale NO2 concentrations across our West Central Scotland
study region. Our model exhibits a 47% improvement in fine scale spatial
prediction of NO2 compared to using the automatic monitors alone, and we use it
to predict NO2 concentrations across West Central Scotland in 2006.
PMID- 26435685
TI - Substrate Topography Guides Pore Morphology Evolution in Nanoporous Gold Thin
Films.
AB - This paper illustrates the effect of substrate topography on morphology evolution
in nanoporous gold (np-Au) thin films. One micron-high silicon ridges with widths
varying between 150 nm to 50 um were fabricated and coated with 500 nm-thick np
Au films obtained by dealloying sputtered gold-silver alloy films. Analysis of
scanning electron micrographs of the np-Au films following dealloying and thermal
annealing revealed two distinct regimes where the ratio of film thickness to
ridge width determines the morphological evolution of np-Au films.
PMID- 26435686
TI - Enhancing imagined contact to reduce prejudice against people with schizophrenia.
AB - Four studies investigated the effect of imagining intergroup contact on prejudice
against people with schizophrenia. Experiments 1 and 2 demonstrated that a
neutral imagined contact task can have negative effects, compared to a control
condition, even when paired with incidental positive information (Experiment 2).
Experiments 3 and 4 demonstrated, however, that an integrated positive imagined
contact scenario does result in less intergroup anxiety and more positive
attitudes, even toward this challenging group. Analyses of participants'
descriptions of the imagined interactions in and across the first three studies
confirm that positive and high quality imagined contact is important for reducing
prejudice, but failing to ensure that imagined contact is positive may have
deleterious consequences. We emphasize the importance of investigating the
quality of the imagined contact experience, and discuss the implications for
using imagined contact as a prejudice-reducing intervention.
PMID- 26435687
TI - Good's buffers as novel phase-forming components of ionic-liquid-based aqueous
biphasic systems.
AB - Aiming at the development of self-buffering and benign extraction/separation
processes, this work reports a novel class of aqueous biphasic systems (ABS)
composed of ionic liquids (ILs) and organic biological buffers (Good's buffers,
GBs). A large array of ILs and GBs was investigated, revealing than only the more
hydrophobic and fluorinated ILs are able to form ABS. For these systems, the
phase diagrams, tie-lines, tie-line lengths, and critical points were determined
at 25 degrees C. The ABS were then evaluated as alternative liquid-liquid
extraction strategies for two amino acids (L-phenylalanine and L-tryptophan). The
single-step extraction efficiencies for the GB-rich phase range between 22.4 and
100.0 % (complete extraction). Contrarily to the most conventional IL-salt ABS,
in most of the systems investigated, the amino acids preferentially migrate for
the most biocompatible and hydrophilic GB-rich phase. Remarkably, in two of the
studied ABS, L-phenylalanine completely partitions to the GB-rich phase while L
tryptophan shows a preferential affinity for the opposite phase. These results
show that the extraction efficiencies of similar amino acids can be tailored by
the design of the chemical structures of the phase-forming components, creating
thus new possibilities for the use of IL-based ABS in biotechnological
separations.
PMID- 26435688
TI - Perspectives on the design of safer nanomaterials and manufacturing processes.
AB - A concerted effort is being made to insert Prevention through Design principles
into discussions of sustainability, occupational safety and health, and green
chemistry related to nanotechnology. Prevention through Design is a set of
principles that includes solutions to design out potential hazards in
nanomanufacturing including the design of nanomaterials, and strategies to
eliminate exposures and minimize risks that may be related to the manufacturing
processes and equipment at various stages of the lifecycle of an engineered
nanomaterial.
PMID- 26435689
TI - Constraints on tensor and scalar couplings from [Formula: see text] and [Formula:
see text].
AB - The angular distribution of [Formula: see text] ([Formula: see text]) depends on
two parameters, the lepton forward-backward asymmetry, [Formula: see text], and
the flat term, [Formula: see text]. Both are strongly suppressed in the standard
model and constitute sensitive probes of tensor and scalar contributions. We use
the latest experimental results for [Formula: see text] in combination with the
branching ratio of [Formula: see text] to derive the strongest model-independent
bounds on tensor and scalar effective couplings to date. The measurement of
[Formula: see text] provides a complementary constraint to that of the branching
ratio of [Formula: see text] and allows us - for the first time - to constrain
all complex-valued (pseudo-)scalar couplings and their chirality-flipped
counterparts in one fit. Based on Bayesian fits of various scenarios, we find
that our bounds even become tighter when vector couplings are allowed to deviate
from the standard model and that specific combinations of angular observables in
[Formula: see text] are still allowed to be up to two orders of magnitude larger
than in the standard model, which would place them in the region of LHCb's
sensitivity.
PMID- 26435690
TI - Adapted Resistance to the Knockdown Effect of shRNA-Derived Srsf3 siRNAs in Mouse
Littermates.
AB - Gene silencing techniques are widely used to control gene expression and have
potential for RNAi-based therapeutics. In this report, transgenic mouse lines
were created for conditional knockdown of Srsf3 (SRp20) expression in liver and
mammary gland tissues by expressing Srsf3-specific shRNAs driven by a U6
promoter. Although a small portion of the transgenic mouse littermates were found
to produce siRNAs in the targeted tissues, most of the transgenic littermates at
two months of age failed to display a knockdown phenotype of Srsf3 expression in
their liver and mammary gland tissues where an abundant level of Srsf3 siRNAs
remained. We saw only one of four mice with liver/mammary gland expressing Srsf3
siRNA displayed a suppressed level of Srsf3 protein, but not the mRNA. Data
indicate that the host resistance to a gene-specific siRNA targeting an essential
gene transcript can be developed in animals, presumably as a physiological
necessity to cope with the hostile perturbation.
PMID- 26435692
TI - Serum C3 Enhances Complement Receptor 3-Mediated Phagocytosis of Borrelia
burgdorferi.
PMID- 26435691
TI - NF-kappaB-DICER-miRs Axis Regulates TNF-alpha Expression in Responses to
Endotoxin Stress.
AB - Unbalanced tumor necrosis factor (TNF)-alpha production is associated with
pathogenesis of a variety of human diseases. However, the molecular pathways
maintaining TNF-alpha homeostasis remain elusive. Here, we report that NF
kappaB/p65-DICER-miRs axis negatively regulates TNF-alpha production. We
demonstrated that NF-kappaB bound to DICER promoter and transcriptionally
regulated DICER expression. In addition, the NF-kappaB/DICER signaling suppresses
TNF-alpha expression by generating mature forms of miR-125b and miR-130a which
negatively regulate TNF-alpha mRNA. Furthermore, we showed that the hepatocyte
specific depletion of Dicer in mice resulted in TNF-alpha overproduction and
sensitized the mice to endotoxin, which could be corrected by administration of
miR-125b mimics. These data suggest that NF-kappaB/p65-DICER-miRs axis involved
in maintaining of TNF-alpha homeostasis, and injection of miR-125b as a potential
therapeutic method for septic shock.
PMID- 26435693
TI - AICAR and Metformin Exert AMPK-dependent Effects on INS-1E Pancreatic beta-cell
Apoptosis via Differential Downstream Mechanisms.
AB - The role of AMP-activated protein kinase (AMPK) in pancreatic beta-cell apoptosis
is still controversial, and the reasons for the discrepancies have not been
clarified. In the current study, we observed the effects of two well-known AMPK
activators 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and metformin,
on apoptosis in rat insulinoma INS-1E cells, and further explored their possible
mechanisms. Both AICAR and metformin protected INS-1E cells from palmitate
induced apoptosis, as reflected by decreases in both cleaved caspase 3 protein
expression and caspase 3/7 activity, and these protective effects were abrogated
by AMPK inhibitor compound C. The protective action of AICAR was probably
mediated by the suppression of triacylglycerol accumulation, increase in Akt
phosphorylation and decrease in p38 MAPK phosphorylation, while metformin might
exert its protective effect on INS-1E cells by decreases in both JNK and p38 MAPK
phosphorylation. All these regulations were dependent on AMPK activation.
However, under standard culture condition, AICAR increased JNK phosphorylation
and promoted INS-1E cell apoptosis in an AMPK-dependent manner, whereas metformin
showed no effect on apoptosis. Our study revealed that AMPK activators AICAR and
metformin exhibited different effects on INS-1E cell apoptosis under different
culture conditions, which might be largely attributed to different downstream
mediators. Our results provided new and informative clues for better
understanding of the role of AMPK in beta-cell apoptosis.
PMID- 26435694
TI - Structure-Based Analysis of the Ligand-Binding Mechanism for DhelOBP21, a C-minus
Odorant Binding Protein, from Dastarcus helophoroides (Fairmaire; Coleoptera:
Bothrideridae).
AB - Odorant binding proteins (OBPs) transport hydrophobic odor molecules across the
sensillar lymph to trigger a neuronal response. Herein, the Minus-C OBP
(DhelOBP21) was characterized from Dastarcus helophoroides, the most important
natural parasitic enemy insect that targets Monochamus alternatus. Homology
modeling and molecular docking were conducted on the interaction between
DhelOBP21 and 17 volatile molecules (including volatiles from pine bark, the
larva of M. alternatus, and the faeces of the larva). The predicted three
dimensional structure showed only two disulfide bridges and a hydrophobic binding
cavity with a short C-terminus. Ligand-binding experiments using N
phenylnaphthylamine (1-NPN) as a fluorescent probe showed that DhelOBP21
exhibited better binding affinities against those ligands with a molecular volume
between 100 and 125 A(3) compared with ligands with a molecular volume between
160 and 185 A(3). Molecules that are too big or too small are not conducive for
binding. We mutated the amino acid residues of the binding cavity to increase
either hydrophobicity or hydrophilia. Ligand-binding experiments and cyber
molecular docking assays indicated that hydrophobic interactions are more
significant than hydrogen-bonding interactions. Although hydrogen-bond
interactions could be predicted for some binding complexes, the hydrophobic
interactions had more influence on binding following hydrophobic changes that
affected the cavity. The orientation of ligands affects binding by influencing
hydrophobic interactions. The binding process is controlled by multiple factors.
This study provides a basis to explore the ligand-binding mechanisms of Minus-C
OBP.
PMID- 26435695
TI - Transgenic Cotton Plants Expressing Double-stranded RNAs Target HMG-CoA Reductase
(HMGR) Gene Inhibits the Growth, Development and Survival of Cotton Bollworms.
AB - RNA interference (RNAi) has been developed as a powerful technique in the
research of functional genomics as well as plant pest control. In this report,
double-stranded RNAs (dsRNA) targeting 3-hydroxy-3-methylglutaryl coenzyme A
reductase (HMGR) gene, which catalyze a rate-limiting enzymatic reaction in the
mevalonate pathway of juvenile hormone (JH) synthesis in cotton bollworm, was
expressed in cotton plants via Agrobacterium tumefaciens-mediated transformation.
PCR and Sothern analysis revealed the integration of HMGR gene into cotton
genome. RT-PCR and qRT-PCR confirmed the high transcription level of dsHMGR in
transgenic cotton lines. The HMGR expression both in transcription and
translation level was significantly downregulated in cotton bollworms
(helicoverpa armigera) larvae after feeding on the leaves of HMGR transgenic
plants. The transcription level of HMGR gene in larvae reared on transgenic
cotton leaves was as much as 80.68% lower than that of wild type. In addition,
the relative expression level of vitellogenin (Vg, crucial source of nourishment
for offspring embryo development) gene was also reduced by 76.86% when the insect
larvae were fed with transgenic leaves. The result of insect bioassays showed
that the transgenic plant harboring dsHMGR not only inhibited net weight gain but
also delayed the growth of cotton bollworm larvae. Taken together, transgenic
cotton plant expressing dsRNAs successfully downregulated HMGR gene and impaired
the development and survival of target insect, which provided more option for
plant pest control.
PMID- 26435696
TI - Temporal Gene Expression Profiles of Pre Blood-Fed Adult Females Immediately
Following Eclosion in the Southern House Mosquito Culex Quinquefasciatus.
AB - Prior to acquisition of the first host blood meal, the anautogenous mosquito
Culex quinquefasciatus requires a period of time in order to prepare for the
blood feeding and, later, vitellogenesis. In the current study, we conducted
whole transcriptome analyses of adult female Culex mosquitoes to identify genes
that may be necessary for both taking of the blood meal, and processing of the
blood meal in adult female mosquitoes Cx. quinquefasciatus. We examined temporal
expression of genes for the periods of post eclosion and prior to the female
freely taking a blood meal. We further evaluated the temporal expression of
certain genes for the periods after the taking of a blood meal to identify genes
that may be necessary for both the taking of the blood meal, and the processing
of the blood meal. We found that adult females required a minimum of 48 h post
eclosion before they freely took their first blood meal. We hypothesized that
gene expression signatures were altered in the mosquitoes before blood feeding in
preparation for the acquisition of the blood meal through changes in multiple
gene expression. To identify the genes involved in the acquisition of blood
feeding, we quantified the gene expression levels of adult female Cx.
quinquefasciatus using RNA Seq throughout a pre-blooding period from 2 to 72 h
post eclosion at 12 h intervals. A total of 325 genes were determined to be
differentially-expressed throughout the pre-blooding period, with the majority of
differentially-expressed genes occurring between the 2 h and 12 h post-eclosion
time points. Among the up-regulated genes were salivary proteins, cytochrome
P450s, odorant-binding proteins, and proteases, while the majority of the down
regulated genes were hypothetical or cuticular genes. In addition, Trypsin was
found to be up-regulated immediately following blood feeding, while trypsin and
chymotrypsin were up-regulated at 48 h and 60 h post blood-feeding, respectively,
suggesting that these proteases are likely involved in the digestion of the blood
meal. Overall, this study reviewed multiple genes that might be involved in the
adult female competency for blood meal acquisition in mosquitoes.
PMID- 26435697
TI - Interaction mechanisms and kinetics of ferrous ion and hexagonal birnessite in
aqueous systems.
AB - BACKGROUND: In soils and sediments, manganese oxides and oxygen usually
participate in the oxidation of ferrous ions. There is limited information
concerning the interaction process and mechanisms of ferrous ions and manganese
oxides. The influence of air (oxygen) on reaction process and kinetics has been
seldom studied. Because redox reactions usually occur in open systems, the
participation of air needs to be further investigated. RESULTS: To simulate this
process, hexagonal birnessite was prepared and used to oxidize ferrous ions in
anoxic and aerobic aqueous systems. The influence of pH, concentration,
temperature, and presence of air (oxygen) on the redox rate was studied. The
redox reaction of birnessite and ferrous ions was accompanied by the release of
Mn2+ and K+ ions, a significant decrease in Fe2+ concentration, and the formation
of mixed lepidocrocite and goethite during the initial stage. Lepidocrocite did
not completely transform into goethite under anoxic condition with pH about 5.5
within 30 days. Fe2+ exhibited much higher catalytic activity than Mn2+ during
the transformation from amorphous Fe(III)-hydroxide to lepidocrocite and goethite
under anoxic conditions. The release rates of Mn2+ were compared to estimate the
redox rates of birnessite and Fe2+ under different conditions. CONCLUSIONS: Redox
rate was found to be controlled by chemical reaction, and increased with
increasing Fe2+ concentration, pH, and temperature. The formation of ferric
(hydr)oxides precipitate inhibited the further reduction of birnessite. The
presence of air accelerated the oxidation of Fe2+ to ferric oxides and
facilitated the chemical stability of birnessite, which was not completely
reduced and dissolved after 18 days. As for the oxidation of aqueous ferrous ions
by oxygen in air, low and high pHs facilitated the formation of goethite and
lepidocrocite, respectively. The experimental results illustrated the single and
combined effects of manganese oxide and air on the transformation of Fe2+ to
ferric oxides. Graphical abstract:Lepidocrocite and goethite were formed during
the interaction of ferrous ion and birnessite at pH 4-7. Redox rate was
controlled by the adsorption of Fe2+ on the surface of birnessite. The presence
of air (oxygen) accelerated the oxidation of Fe2+ to ferric oxides and
facilitated the chemical stability of birnessite.
PMID- 26435698
TI - Swedish student nurses' perception of peer learning as an educational model
during clinical practice in a hospital setting-an evaluation study.
AB - BACKGROUND: Peer learning, a collaborative learning model has no tradition in
clinical education for undergraduate student nurses in Sweden, and little is
reported of the student experience. An increasing number of students have led to
a pressing need for preceptors and clinical placements thus, highlighting the
need for a supportive educational model. The objectives for the current study
were to explore how student nurses' evaluated peer learning as an educational
model during clinical practice in a hospital setting, and to compare perceptions
among student nurses from year one and three. METHODS: A questionnaire developed
for the purpose of this study was developed and responded to by 62 (year one) and
73 (year three) student nurses. Data were collected between 2011 and 2013. The
questionnaire contained six open- ended and eight closed questions on a four
point Likert-scale. Written responses were analysed by content analysis and the
closed questions by using descriptive statistics. Mann-Whitney U-test was used to
examine differences in relation to students from year one and three. RESULTS: The
peer learning experience was evaluated in a positive way. Statistical
significance differences were shown for two out of eight closed questions. The
peer learning activities were evaluated as supportive and relevant for learning.
Three categories emerged from the content analysis: "a feeling of safety", "a
sense of competition" and "the learning experience". CONCLUSION: A feeling of
safety seems to be connected to students' perception of increased learning and
independence. However, the sense of negative competition needs to be addressed
when students are prepared for the teaching and learning activities in the peer
learning model. Finally, what needs to be further investigated is what challenges
and opportunities the peer learning model presents to preceptors.
PMID- 26435699
TI - School holidays: examining childhood, gender norms, and kinship in children's
shorter-term residential mobility in urban Zambia.
AB - This article discusses a practice of child residential mobility in Zambia that is
frequently overlooked in migration studies and difficult to capture through
standard survey methods: the practice of 'going on holiday' to the homes of
relatives during breaks in the school term. Drawing on child-centered and
quantitative research, this article examines the multiple dimensions of 'going on
holiday' for children living in a low-income urban settlement in Lusaka. Findings
suggest that the practice was gendered and may map onto changing norms in
schooling in Zambia. Within a context where resources are severely constrained,
going on holiday may serve as one means for cultivating reciprocity, sharing the
burden of care and household labor, and strengthening kin ties. This work further
demonstrates the importance of using locally meaningful terms and practices in
survey research where general questions about children's mobility may fail to
capture the nature and extent of children's movements.
PMID- 26435700
TI - Obesity-associated hypertension is ameliorated in patients with TLR4 single
nucleotide polymorphism (SNP) rs4986790.
AB - BACKGROUND: Obesity is strongly associated with hypertension. Despite numerous
mechanistic links the association is not fully understood. Western diet increases
uptake of Toll-Like receptor 4 (TLR4) ligands such as free fatty acids or
endotoxin. We recently demonstrated that TLR4 ligands are involved in the
development of hypertension. We hypothesized that TLR4 ligands are involved in
obesity-associated hypertension and investigated the TLR4 single nucleotide
polymorphism (SNP rs 498790). This SNP is frequent, associated with
cardiovascular disease and characterized by blunted response upon exposure to
TLR4 ligands. METHODS: We investigated 3657 patients undergoing coronary
angiography. Blood pressure was determined in standardized manner prior
angiography. The diagnosis of hypertension was based on record data. Patients
were characterized for TLR4 single nucleotide polymorphism (SNP) rs4986790.
Patients were stratified according to quartiles of Body mass index (BMI) and
according to the polymorphism. The association between the TLR4 polymorphism and
blood pressure in obese patients (BMI > 30 kg/m(2)) was investigated by
multivariate regression analysis. RESULTS: Out of 3657 patients 3017 patients
fulfilled inclusion criteria. In the whole cohort a significant increase of SBP,
pulse pressure and diagnosis of hypertension was observed across BMI quartiles.
By contrast, no significant increase of SBP, pulse pressure or diagnosis of
hypertension was observed in the 319 cases with TLR4 SNP rs4986790 across BMI
quartiles. These obese cases had significantly lower SBP, lower pulse pressure
(7.0 and 7.6 mmHg) and less diagnosis of hypertension as controls. In obesity the
TLR4 SNP rs4986790 was an independent predictor of SBP. CONCLUSION: Systolic
blood pressure increase with obesity was blunted in cases with TLR4 SNP
rs4986790.
PMID- 26435701
TI - Role of genomics in eliminating health disparities.
AB - The Texas Center for Health Disparities, a National Institute on Minority Health
and Health Disparities Center of Excellence, presents an annual conference to
discuss prevention, awareness education, and ongoing research about health
disparities both in Texas and among the national population. The 2014 Annual
Texas Conference on Health Disparities brought together experts in research,
patient care, and community outreach on the "Role of Genomics in Eliminating
Health Disparities." Rapid advances in genomics and pharmacogenomics are leading
the field of medicine to use genetics and genetic risk to build personalized or
individualized medicine strategies. We are at a critical juncture of ensuring
such rapid advances benefit diverse populations. Relatively few forums have been
organized around the theme of the role of genomics in eliminating health
disparities. The conference consisted of three sessions addressing "Gene
Environment Interactions and Health Disparities," "Personalized Medicine and
Elimination of Health Disparities," and "Ethics and Public Policy in the Genomic
Era." This article summarizes the basic science, clinical correlates, and public
health data presented by the speakers.
PMID- 26435702
TI - Validation of a new predictive risk model: measuring the impact of the major
modifiable risks of death for patients and populations.
AB - BACKGROUND: Modifiable risks account for a large fraction of disease and death,
but clinicians and patients lack tools to identify high risk populations or
compare the possible benefit of different interventions. METHODS: We used data on
the distribution of exposure to 12 major behavioral and biometric risk factors
inthe US population, mortality rates by cause, and estimates of the proportional
hazards of risk factor exposure from published systematic reviews to develop a
risk prediction model that estimates an adult's 10 year mortality risk compared
to a population with optimum risk factors. We compared predicted risk to observed
mortality in 8,241 respondents in NHANES 1988-1994 and NHANES 1999-2004 with
linked mortality data up to the end of 2006. RESULTS: Predicted risk showed good
discrimination with an area under the receiver operating characteristic (ROC)
curve of 0.84 (standard error 0.01) for women and 0.84 (SE 0.01) for men. Across
deciles of predicted risk, mortality was accurately predicted in men ((Chi (2)
statistic = 12.3 for men, p=0.196) but slightly overpredicted in the highest
decile among women (Chi (2) statistic = 22.8, p=0.002). Mortality risk was highly
concentrated; for example, among those age 30-44 years, 5.1 % (95 % CI 4.1 % -
6.0 %) of the male and 5.9 % (95 % CI 4.8 % - 6.9 %) of the female population
accounted for 25 % of the risk of death. CONCLUSION: The risk model accurately
predicted mortality in a representative sample of the US population and could be
used to help inform patient and provider decision-making, identify high risk
groups, and monitor the impact of efforts to improve population health.
PMID- 26435703
TI - Control of Assembly of Dihydropyridyl and Pyridyl Molecules via Directed Hydrogen
Bonding.
AB - The crystallization of two dihydropyridyl molecules, 1,4-bis(4-(3,5-dicyano-2,6
dipyridyl)dihydropyridyl)benzene ([C40H24N10].2DMF, 1.2DMF; DMF =
dimethylformamide) and 1,4-bis(4-(3,5-dicyano-2,6
dipyridyl)dihydropyridyl)phenylbenzene ([C46H28N10].2DMF, 3.2DMF), and their
respective oxidized pyridyl analogues, 1,4-bis(4-(3,5-dicyano-2,6
dipyridyl)pyridyl)benzene ([C40H20N10], 2) and 1,4-bis(4-(3,5-dicyano-2,6
dipyridyl)pyridyl)phenylbenzene ([C46H24N10].DMF, 4.DMF), has been achieved under
solvothermal conditions. The dihydropyridyl molecules are converted to their
pyridyl products via in situ oxidative dehydrogenation in solution. The
structures of the four molecules have been fully characterized by single crystal
and powder X-ray diffraction. The oxidized pyridyl products, 2 and 4, are more
elongated due to aromatization of the dihydropyridyl rings at each end of their
parent molecules 1 and 3, respectively. The solid-state supramolecular structures
of the pyridyl molecules are distinct from the dihydropyridyl molecules in terms
of their hierarchical assembly via hydrogen bonding due to the loss of primary N
H hydrogen bond donors in the two electron oxidized tectons. Overall, the
geometrically shorter molecules 1 and 3 display close-packed structures, whereas
the more extended 2 and 4 assemble into more open supramolecular systems.
PMID- 26435704
TI - Nontyphoidal Salmonella: An Occupational Hazard for Clinical Laboratory Workers.
AB - Laboratory-acquired infections due to nontyphoidal Salmonella are rare. Yet,
recent outbreaks in microbiology teaching laboratories show that these species
are still an appreciable occupational hazard for laboratory employees. This
article presents two cases of nontyphoidal Salmonella that occurred at the
authors' institution-an infected patient and a clinical laboratory worker who
acquired the infection by handling this patient's specimens.
PMID- 26435705
TI - Histone post-translational modifications in frontal cortex from human donors with
Alzheimer's disease.
AB - BACKGROUND: Alzheimer's disease (AD) is the sixth leading cause of death and the
most costly disease in the US. Despite the enormous impact of AD, there are no
treatments that delay onset or stop disease progression currently on the market.
This is partly due to the complexity of the disease and the largely unknown
pathogenesis of sporadic AD, which accounts for the vast majority of cases.
Epigenetics has been implicated as a critical component to AD pathology and a
potential "hot spot" for treatments. Histone post-translational modifications
(PTMs) are a key element in epigenetic regulation of gene expression and are
known to be associated with the pathology of numerous diseases. Investigation of
histone PTMs can help elucidate AD pathology and identify targets for therapies.
RESULTS: A multiple reaction monitoring mass spectrometry assay was used to
measure changes in abundance of several histone PTMs in frontal cortex from human
donors affected with AD (n = 6) and age-matched, normal donors (n = 6). Of the
changes observed, notable decreases in methylation of H2B residue K108 by 25 %
and H4 residue R55 by 35 % were measured and are likely associated with hydrogen
bonding networks important for nucleosome stability. Additionally, a 91 %
increase in ubiquitination of K120 on H2B was measured as well as an apparent
loss in acetylation of the region near the N-terminus of H4. Our method of
quantification was also determined to be precise and robust, signifying measured
changes were representative of true biological differences between donors and
sample groups. CONCLUSION: We are the first to report changes in methylation of
H2B K108, methylation of H4 R55, and ubiquitination of H2B K120 in frontal cortex
from human donors with AD. These notable PTM changes may be of great importance
in elucidating the epigenetic mechanism of AD as it relates to disease pathology.
Beyond the structural and functional impacts of the changes we have measured, the
sites of altered PTMs may be used to identify enzymes responsible for their
modulation, which could be used as prospective drug targets for highly specific
AD therapies.
PMID- 26435706
TI - Current approaches to cyanotoxin risk assessment and risk management around the
globe.
AB - Toxic cyanobacteria became more widely recognized as a potential health hazard in
the 1990s, and in 1998 the World Health Organization (WHO) first published a
provisional Guideline Value of 1 MUg L-1 for microcystin-LR in drinking-water. In
this publication we compare risk assessment and risk management of toxic
cyanobacteria in 17 countries across all five continents. We focus on the three
main (oral) exposure vehicles to cyanotoxins: drinking-water, water related
recreational and freshwater seafood. Most countries have implemented the
provisional WHO Guideline Value, some as legally binding standard, to ensure the
distribution of safe drinking-water with respect to microcystins. Regulation,
however, also needs to address the possible presence of a wide range of other
cyanotoxins and bioactive compounds, for which no guideline values can be derived
due to insufficient toxicological data. The presence of microcystins (commonly
expressed as microcystin-LR equivalents) may be used as proxy for overall
guidance on risk management, but this simplification may miss certain risks, for
instance from dissolved fractions of cylindrospermopsin and cyanobacterial
neurotoxins. An alternative approach, often taken for risk assessment and
management in recreational waters, is to regulate cyanobacterial presence - as
cell numbers or biomass - rather than individual toxins. Here, many countries
have implemented a two or three tier alert level system with incremental
severity. These systems define the levels where responses are switched from
Surveillance to Alert and finally to Action Mode and they specify the short-term
actions that follow. Surface bloom formation is commonly judged to be a
significant risk because of the elevated concentration of microcystins in a scum.
Countries have based their derivations of legally binding standards, guideline
values, maximally allowed concentrations (or limits named otherwise) on very
similar scientific methodology, but underlying assumptions such as bloom
duration, average body size and the amount of water consumed while swimming vary
according to local circumstances. Furthermore, for toxins with incomplete
toxicological data elements of expert judgment become more relevant and this also
leads to a larger degree of variation between countries' thresholds triggering
certain actions. Cyanobacterial blooms and their cyanotoxin content are a highly
variable phenomenon, largely depending on local conditions, and likely
concentrations can be assessed and managed best if the specific conditions of the
locality are known and their impact on bloom occurrence are understood. Risk
Management Frameworks, such as for example the Water Safety Plan concept of the
WHO and the 'bathing water profile' of the European Union are suggested to be
effective approaches for preventing human exposure by managing toxic
cyanobacteria from catchment to consumer for drinking water and at recreational
sites.
PMID- 26435707
TI - Model of Polarization Selectivity of the Intermediate Filament Optical Channels.
AB - Recently we have analyzed light transmission and spectral selectivity by optical
channels in Muller cells and other transparent cells, proposing a model of their
structure, formed by specialized intermediate filaments [1,2]. Our model
represents each optical channel by an axially symmetric tube with conductive
walls. Presently, we analyze the planar polarization selectivity in long
nanostructures, using the previously developed approach extended to structures of
the elliptic cross-section. We find that the output light polarization angle
depends on the a/b ratio, with a and b the semiaxes of the ellipse. Experimental
tests used a Cr nano-strip device to evaluate the transmitted light polarization.
The model adapted to the experimental geometry provided an accurate fit of the
experimental results.
PMID- 26435708
TI - Natural infection of phlebotomines (Diptera: Psychodidae) by Leishmania
(Leishmania) amazonensis in an area of ecotourism in Central-Western Brazil.
AB - BACKGROUND: Bonito municipality, known as an area of ecoturism, in Mato Grosso do
Sul state, Brazil, is also a focus of visceral and cutaneous leishmaniases, with
cases registered in both human and canine populations. This study sought to
investigate natural infection by flagellate forms of Leishmania in phlebotomines
of the urban area of Bonito. FINDINGS: Sand flies were collected fortnightly from
October 2005 to July 2006 with modified automatic light traps installed in
peridomiciles and animal shelters in the center and on the outskirts of the city.
The females were dissected and their guts observed under an optical microscope. A
total of 1977 specimens were captured, Lutzomyia longipalpis (88.4 %) and
Bichromomyia flaviscutelata (3.0 %) being the most frequent species. Bi.
flaviscutellata was found infected by flagellates that were identified as
Leishmania (Leishmania) amazonensis by indirect immunofluorescence reaction,
employing monoclonal antibodies and the biotin-avidin system. This is the first
report of natural infection by L. amazonensis in Bi. flaviscutellata in a
Brazilian urban area. CONCLUSIONS: As Bi. flaviscutellata is only slightly
attracted by humans, the transmission of L. amazonensis in the study area may
have a zoonotic character; however, the sympatric occurrence of this parasite and
Lu. longipalpis should be taken into consideration by the local health
authorities since this sand fly has already been found with L. amazonensis DNA in
a focus of canine visceral leishmaniasis in Bonito municipality.
PMID- 26435709
TI - Review of the Structural and Dynamic Mechanisms of PPARgamma Partial Agonism.
AB - PPARgamma (peroxisome proliferator activated receptor gamma) is a ligand
activated transcription factor of the nuclear receptor superfamily that controls
the expression of a variety of genes involved in fatty acid metabolism,
adipogenesis, and insulin sensitivity. While endogenous ligands of PPARgamma
include fatty acids and eicosanoids, synthetic full agonists of the receptor,
including members of the thiazolidinedione (TZD) class, have been widely
prescribed for the treatment of type II diabetes mellitus (T2DM). Unfortunately,
the use of full agonists has been hampered by harsh side effects with some
removed from the market in many countries. In contrast, partial agonists of
PPARgamma have been shown to retain favourable insulin sensitizing effects while
exhibiting little to no side effects and thus represent a new potential class of
therapeutics for the treatment of T2DM. Partial agonists have been found to not
only display differences in transcriptional and cellular outcomes, but also act
through distinct structural and dynamic mechanisms within the ligand binding
cavity compared to full agonists.
PMID- 26435710
TI - Genome-Wide Comparative Analysis of Flowering-Related Genes in Arabidopsis,
Wheat, and Barley.
AB - Early flowering is an important trait influencing grain yield and quality in
wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) in short-season
cropping regions. However, due to large and complex genomes of these species,
direct identification of flowering genes and their molecular characterization
remain challenging. Here, we used a bioinformatic approach to predict flowering
related genes in wheat and barley from 190 known Arabidopsis (Arabidopsis
thaliana (L.) Heynh.) flowering genes. We identified 900 and 275 putative
orthologs in wheat and barley, respectively. The annotated flowering-related
genes were clustered into 144 orthologous groups with one-to-one, one-to-many,
many-to-one, and many-to-many orthology relationships. Our approach was further
validated by domain and phylogenetic analyses of flowering-related proteins and
comparative analysis of publicly available microarray data sets for in silico
expression profiling of flowering-related genes in 13 different developmental
stages of wheat and barley. These further analyses showed that orthologous gene
pairs in three critical flowering gene families (PEBP, MADS, and BBX) exhibited
similar expression patterns among 13 developmental stages in wheat and barley,
suggesting similar functions among the orthologous genes with sequence and
expression similarities. The predicted candidate flowering genes can be confirmed
and incorporated into molecular breeding for early flowering wheat and barley in
short-season cropping regions.
PMID- 26435712
TI - Breeding Sites of Aedes aegypti: Potential Dengue Vectors in Dire Dawa, East
Ethiopia.
AB - Background and Objectives. Entomological survey was carried out from May-June to
September-October 2014 to investigate the presence of dengue vectors in discarded
tires and artificial water containers in houses and peridomestic areas. Methods.
A cross-sectional immature stage survey was done indoors and outdoors in 301
houses. Mosquito larval sampling was conducted using pipette or dipper depending
on container types. Larvae were identified morphologically and larval indices
were also calculated. Results. A total of 750 containers were inspected, and of
these 405 were positive for mosquito larvae. A total of 1,873 larvae were
collected and morphologically identified as Aedes aegypti (n = 1580: 84.4%) and
Culex (n = 293: 15.6%). The larval indices, house index, container index, and
breteau index, varied from 33.3 to 86.2, from 23.2 to 73.9, and from 56.5 to
188.9, respectively. Conclusion. Aedes aegypti is breeding in a wide range of
artificial containers. To control these mosquitoes, the integration of different
methods should be taken into consideration.
PMID- 26435711
TI - Melatonin and Ischemic Stroke: Mechanistic Roles and Action.
AB - Stroke is one of the most devastating neurological disabilities and brain's
vulnerability towards it proves to be fatal and socio-economic loss of millions
of people worldwide. Ischemic stroke remains at the center stage of it, because
of its prevalence amongst the several other types attacking the brain. The
various cascades of events that have been associated with stroke involve
oxidative stress, excitotoxicity, mitochondrial dysfunction, upregulation of
Ca(2+) level, and so forth. Melatonin is a neurohormone secreted by pineal and
extra pineal tissues responsible for various physiological processes like sleep
and mood behaviour. Melatonin has been implicated in various neurological
diseases because of its antioxidative, antiapoptotic, and anti-inflammatory
properties. We have previously reviewed the neuroprotective effect of melatonin
in various models of brain injury like traumatic brain injury and spinal cord
injury. In this review, we have put together the various causes and consequence
of stroke and protective role of melatonin in ischemic stroke.
PMID- 26435713
TI - Switching from Twice-Daily Basal Insulin Injections to Once-Daily Insulin
Degludec Injection for Basal-Bolus Insulin Regimen in Japanese Patients with Type
1 Diabetes: A Pilot Study.
AB - The aim of this study was to investigate the efficacy of insulin degludec used
for basal-bolus insulin regimen after switching from twice-daily basal insulin in
Japanese patients with type 1 diabetes mellitus. The subjects were 22 type 1
diabetes patients treated with basal-bolus insulin regimen with twice-daily basal
insulin. Basal insulin was switched to once-daily injection of insulin degludec
with 10% dose reduction. HbA1c and fasting plasma glucose (FPG) were measured
before and 12 weeks after switching. The frequency of hypoglycemic episodes,
standard deviation (SD) of blood glucose, and mean of daily difference (MODD)
were evaluated by continuous glucose monitoring (CGM) before and 4 weeks after
switching. HbA1c and FPG before and 12 weeks after switching were comparable
(HbA1c 8.5 +/- 1.4 versus 8.7 +/- 1.6%, P = 0.28; FPG 203.2 +/- 81.2 versus 206.5
+/- 122.4 mg/dL, P = 0.91). The frequency of hypoglycemia during nighttime was
not significantly different at 4 weeks after switching (14.4 +/- 17.0 versus 11.1
+/- 15.0%, P = 0.45). In addition, SD and MODD before and 4 weeks after switching
were also comparable. In conclusion, glycemic control under once-daily insulin
degludec injection was almost comparable to that under twice-daily basal insulin
injections in Japanese type 1 diabetes patients. This study was registered with
ID: UMIN000010474.
PMID- 26435714
TI - Thyroid Dysfunction and Associated Risk Factors among Nepalese Diabetes Mellitus
Patients.
AB - Objectives. To assess thyroid function and associated risk factors in Nepalese
diabetes mellitus patients. Methods. A cross-sectional study was carried out
among 419 diabetes mellitus patients at B. P. Koirala Institute of Health
Sciences, Dharan, Nepal. Information on demographic and anthropometric variables
and risk factors for thyroid dysfunction was collected. Blood samples were
analysed to measure thyroid hormones, blood sugar, and lipid profile. Results.
Prevalence rate of thyroid dysfunction was 36.03%, with subclinical
hypothyroidism (26.5%) as the most common thyroid dysfunction. Thyroid
dysfunction was much common in females (42.85%) compared to males (30.04%) (p =
0.008) and in type 1 diabetes (50%) compared to type 2 diabetes mellitus (35.41%)
(p = 0.218). Diabetic patients with thyroid dysfunction had higher total
cholesterol, HDL cholesterol, and LDL cholesterol in comparison to patients
without thyroid dysfunction. Significant risk factors for thyroid dysfunction,
specifically hypothyroidism (overt and subclinical), were smoking (relative risk
of 2.56 with 95% CI (1.99-3.29, p < 0.001)), family history of thyroid disease
(relative risk of 2.57 with 95% CI (2.0-3.31, p < 0.001)), and female gender
(relative risk of 1.44 with 95% CI (1.09-1.91, p = 0.01)). Conclusions. Thyroid
dysfunction is common among Nepalese diabetic patients. Smoking, family history
of thyroid disease, and female gender are significantly associated with thyroid
dysfunction.
PMID- 26435715
TI - Determinants of Overall and Progression-Free Survival of Nigerian Patients with
Philadelphia-Positive Chronic Myeloid Leukemia.
AB - Objective. The tyrosine kinase inhibitors have markedly changed the disease
course for patients with Ph(+) and/or BCR-ABL1 (+) chronic myeloid leukemia
(CML). This study was embarked upon to assess the long-term effects of imatinib
therapy on survival in adult Nigerian patients with CML. Methods. All adult
patients on imatinib (400-600 mg) seen from July 2003 to December 2010 were
assessed. Male/female distribution was 171/101, with a median age of 38 (range,
20-75) years. Overall survival (OS) and progression-free survival (PFS) were
determined using the Kaplan-Meier techniques. Results. Of all the 272 patients,
205 were in chronic phase, 54 in accelerated phase, and five in blastic phase, at
commencement of imatinib. As at December 2010, 222 were alive. OS at 1 and 5
years was 94% and 63%, while PFS was 89% and 54%, respectively. Similarly,
amongst the 205 patients in chronic phase, OS at 1 and 5 years was 97% and 68%,
while PFS was 92% and 57%. Conclusion. Imatinib's place as first-line therapy in
the treatment of CML has further been reinforced in our patients, with improved
survival and reduced morbidity, comparable with outcomes in other populations.
PMID- 26435716
TI - Pulmonary Silicosis Presents with Pleural Effusion.
AB - Silica and silicate mineral dust inhalation can cause a variety of
histopathological changes in the lungs and pleura. These include pulmonary
silicotic nodules, interstitial infiltrate, fibrosis, and pleural thickening.
Pleural effusion is an extremely rare presentation of silicosis. To our best
knowledge, there have been only 2 cases of silicosis with pleural effusion
reported in medical literature. Herein, we describe a case of a 77-year-old male
with almost 50 years' history of occupational silica exposure. He presented with
a 4-week history of exertional shortness of breath. He is a lifetime nonsmoker,
with no known other significant pulmonary disease. He had chest X-ray which
showed a right lung infiltrate and bilateral pleural thickening and effusion.
Chest CT showed moderate-sized bilateral pleural effusion and thickening with
multiple bilateral intrapulmonary nodules seen. He had undergone extensive workup
and was diagnosed with silicosis.
PMID- 26435717
TI - Prevalence and Pattern of Soil-Transmitted Helminthic Infection among Primary
School Children in a Rural Community in Imo State, Nigeria.
AB - Background. Soil-transmitted helminthic infection is a common public health
challenge of primary school children in resource challenged and developing
countries. Our aim was to determine the prevalence and pattern of soil
transmitted helminthic infection among primary school children in a rural
community in Imo State, Nigeria. Method. The study involved a cross-sectional
survey of 284 primary school children in a rural community. Results. The overall
prevalence of soil-transmitted helminthic infection (STHI) was 30.3%. Of all
STHIs, hookworm was the commonest geohelminth observed, 81 (94.2%). The
prevalence of soil-transmitted helminthic infection was more in males, 58
(38.4%), than in females, 28 (21.1%). This difference was statistically
significant (P = 0.001). Conclusion. The high prevalence rate of soil-transmitted
helminthic infection amongst the study population is worrisome. There is need for
organized and routine deworming among school children in the community.
PMID- 26435718
TI - Safety of a Bioactive Polyphenol Dietary Supplement in Pediatric Subjects with
Acute Diarrhoea.
AB - The hematological and clinical chemistry profile for children aged 6 months to 5
years with acute diarrhoea was measured in a double blind clinical trial.
Subjects were randomized to the study group (N = 44) given a bioactive polyphenol
dietary supplement in oral rehydration solution (ORS) or to the control group (N
= 41) given distilled water as a placebo in ORS twice daily for up to 4 days. All
subjects received 10 mg zinc daily for the 4 days in the study. Venous blood was
collected for complete blood count, electrolytes, liver function, and creatinine
upon enrollment (baseline) and at the end of 4 days (end of study); mean values
were compared by 95% confidence intervals. Overall, blood factors measured either
remained the same over the 4 days or increased or decreased at the same levels
between the two groups during the study period. All values were within accepted
ranges for paediatric subjects except serum AST (SGOT), where the mean value of
the study group approached the upper bound of the range on day 4 but was
comparable to the value of the control group. Consumption of this supplement
twice daily for 4 days is safe for children and infants.
PMID- 26435719
TI - Peptide-Induced Amyloid-Like Conformational Transitions in Proteins.
AB - Changes in protein conformation can occur both as part of normal protein
functioning and during disease pathogenesis. The most common conformational
diseases are amyloidoses. Sometimes the development of a number of diseases which
are not traditionally related to amyloidoses is associated with amyloid-like
conformational transitions of proteins. Also, amyloid-like aggregates take part
in normal physiological processes such as memorization and cell signaling.
Several primary structural features of a protein are involved in conformational
transitions. Also the protein proteolytic fragments can cause the conformational
transitions in the protein. Short peptides which could be produced during the
protein life cycle or which are encoded by short open reading frames can affect
the protein conformation and function.
PMID- 26435720
TI - Retracted: Immunopathology and Immunogenetics of Allergic Bronchopulmonary
Aspergillosis.
AB - [This retracts the article DOI: 10.1155/2011/785983.].
PMID- 26435721
TI - The Falsified Medicines Directive: How to secure your supply chain.
PMID- 26435722
TI - Neuroprotective Effects of Cistanches Herba Therapy on Patients with Moderate
Alzheimer's Disease.
AB - Cistanches Herba (CH) is thought to be a "Yang-invigorating" material in
traditional Chinese medicine. We evaluated neuroprotective effects of Cistanches
Herba on Alzheimer's disease (AD) patients. Moderate AD participants were divided
into 3 groups: Cistanches Herba capsule (CH, n = 10), Donepezil tablet (DON, n =
8), and control group without treatment (n = 6). We assessed efficacy by MMSE and
ADAS-cog, and investigated the volume changes of hippocampus by 1.5 T MRI scans.
Protein, mRNA levels, and secretions of total-tau (T-tau), tumor necrosis factor
alpha (TNF-alpha), and interleukin- (IL) 1beta (IL-1beta) in cerebrospinal fluid
(CSF) were detected by Western blot, RT-PCR, and ELISA. The scores showed
statistical difference after 48 weeks of treatment compared to control group.
Meanwhile, volume changes of hippocampus were slight in drug treatment groups but
distinct in control group; the levels of T-tau, TNF-alpha, and IL-1beta were
decreased compared to those in control group. Cistanches Herba could improve
cognitive and independent living ability of moderate AD patients, slow down
volume changes of hippocampus, and reduce the levels of T-tau, TNF-alpha, and IL
1beta. It suggested that Cistanches Herba had potential neuroprotective effects
for moderate AD.
PMID- 26435723
TI - The Chondroprotective Role of TMF in PGE2-Induced Apoptosis Associating with
Endoplasmic Reticulum Stress.
AB - Endoplasmic reticulum stress (ERS) has been demonstrated to exhibit a critical
role in osteoarthritic chondrocytes. Whether 5,7,3',4'-tetramethoxyflavone (TMF)
plays the chondroprotective role in inhibition of PGE2-induced chondrocytes
apoptosis associating with ERS has not been reported. To investigate this, the
activation of PERK, ATF6, and IRE1 signaling pathways in ERS in chondrocytes
pretreated with PGE2 was studied. By treatment with PGE2, the chondrocytes
apoptosis was significantly increased, the proapoptotic CHOP and JNK were
upregulated, the prosurvival GRP78 and XBP1 were downregulated, and GSK-3beta was
also upregulated. However, TMF exhibited the effectively protective functions via
counteracting these detrimental effects of PGE2. Finally, the inflammatory
cytokine PGE2 can activate ERS signaling and promote chondrocytes apoptosis,
which might be associated with upregulation of GSK-3beta. TMF exhibits a
chondroprotective role in inhibiting PGE2-induced ERS and GSK-3beta.
PMID- 26435724
TI - Effect of Aqueous Extract from Morinda officinalis F. C. How on Microwave-Induced
Hypothalamic-Pituitary-Testis Axis Impairment in Male Sprague-Dawley Rats.
AB - The present study aimed to assess the protective effects of aqueous extract from
Morinda officinalis F. C. How on microwave-induced reproductive impairment in
male rats. Microwave exposure injury was induced by exposure of 900 MHz
microwaves at 218 MUm/cm(2)radiation densities, 24 hours/day for 10 days. Male
Sprague-Dawley rats were randomized to: normal control, microwave exposure model,
or water layer or ethyl acetate layer of aqueous extract 40 g/kg treatment
groups. After 2 weeks of treatment, sexual performance, serum levels of
gonadotrophin-releasing hormone (GnRH), luteinizing hormone (LH), follicle
stimulating hormone (FSH) or testosterone, morphological analysis of testis and
epididymis, and GnRH protein expression in the hypothalamus were measured.
Pretreatment with water layer of aqueous extract 40 g/kg significantly improved
sexual performance, increased serum testosterone level, and decreased LH and GnRH
level compared with microwave exposed model rats (all P < 0.05). Water layer of
aqueous extract treatment significantly increased seminiferous cell or sperm
number in testis and epididymis. Protein expression of GnRH in the hypothalamus
significantly decreased in the water layer of aqueous extract treated group (P <
0.05). Ethyl acetate layer of aqueous extract did not show obvious effects on the
measured parameters. These findings suggest that water layer of aqueous extract
40 g/kg ameliorates microwave-reduced reproductive impairment.
PMID- 26435725
TI - External Application of Traditional Chinese Medicine for Venous Ulcers: A
Systematic Review and Meta-Analysis.
AB - Objective. To evaluate the effectiveness of external application of traditional
Chinese medicine (EA-TCM) on venous ulcers. Methods. Seven databases were
searched until April 2015 for randomized controlled trials (RCTs) of EA-TCM for
venous ulcers. Risk of bias was assessed using Cochrane Handbook guidelines.
Study outcomes were presented as risk ratios (RRs) for dichotomous data or mean
differences (MDs) for continuous data. Results. Sixteen of 193 potentially
relevant trials met the inclusion criteria; however, their methodological
qualities were low. Comparison of the same intervention strategies revealed
significant differences in total effectiveness rates between EA-TCM and
conventional therapy groups (RR = 1.22, 95% confidence interval [CI] = 1.16-1.29,
and P < 0.00001). Compared to conventional therapy, EA-TCM combined with
conventional therapy had a superior total effectiveness rate (RR = 1.11, 95% CI =
1.04-1.19, and P = 0.003). There were no significant differences in recurrence
rates during followup and final pain measurements between the experimental and
those in the control groups (RR = 0.86, 95% CI = 0.31-2.39, and P = 0.85; MD
0.75, 95% CI = -2.15-0.65, and P = 0.29). Conclusion. The evidence that EA-TCM is
an effective treatment for venous ulcers is encouraging, but not conclusive due
to the low methodological quality of the RCTs. Therefore, more high-quality RCTs
with larger sample sizes are required.
PMID- 26435726
TI - The immunological footprint of CMV in HIV-1 patients stable on long-term ART.
AB - BACKGROUND: Most HIV-infected persons are cytomegalovirus (CMV) seropositive and
retain latent virus that can be reactivated by immune activation. Their T cell
populations express markers reflecting a late stage of differentiation, but the
contributions of HIV and CMV to this profile are unclear. We investigated the
immunological "footprint" of CMV in HIV patients who had a history of extreme
immunodeficiency but were now stable on antiretroviral therapy (ART). RESULTS:
Twenty CMV seropositive HIV patients >50 years old with nadir CD4 T-cell counts
<200 cells/MUl were studied after >12 years on ART. 16 CMV seropositive and 9 CMV
seronegative healthy controls were included. CMV antibody titres were higher in
HIV patients than controls (P < 0.001-0.003). Levels of soluble B-cell activating
factor (sBAFF) were elevated in patients (P = 0.002) and correlated with levels
of CMV antibodies (P = 0.03-0.002), with no clear relationship in controls. CD8 T
cell IFNgamma responses to the IE1 peptide (VLE) remained elevated in HIV
patients (P = 0.005). The CD57(+)CD45RA(+)CD27(-) phenotype of CD8 T-cells
correlated with age (r = 0.60, P = 0.006), antibodies against CMV IE1 protein (r
= 0.44, P = 0.06) and CD4 T-cell IFNgamma response to CMV lysate (r = 0.45, P =
0.05). CONCLUSIONS: Humoral and T-cell responses to CMV remained elevated in HIV
patients after >12 years on ART. Age and presence of CMV disease influenced CD8 T
cell phenotypes. Elevated levels of sBAFF may be a consequence of HIV disease and
contribute to high titres of CMV antibody.
PMID- 26435727
TI - Defining the fitness of HIV-1 isolates with dual/mixed co-receptor usage.
AB - BACKGROUND: CCR5-using (r5) HIV-1 predominates during asymptomatic disease
followed by occasional emergence of CXCR4-using (x4) or dual tropic (r5x4) virus.
We examined the contribution of the x4 and r5 components to replicative fitness
of HIV-1 isolates. METHODS: Dual tropic r5x4 viruses were predicted from average
HIV-1 env sequences of two primary subtype C HIV-1 isolates (C19 and C27) and
from two patient plasma samples (B12 and B19). Chimeric Env viruses with an NL4-3
backbone were constructed from the B12 and B19 env sequences. To determine
replicative fitness, these primary and chimeric dual tropic HIV-1 were then
competed against HIV-1 reference isolates in U87.CD4 cells expressing CXCR4 or
CCR5 or in PBMCs +/- entry inhibitors. Contribution of the x4 and r5 clones
within the quasispecies of these chimeric or primary HIV-1 isolates were then
compared to the frequency of x4, r5, and dual tropic clones within the
quasispecies as predicted by phenotypic assays, clonal sequencing, and 454 deep
sequencing. RESULTS: In the primary HIV-1 isolates (C19 and C27), subtype C dual
tropic clones dominated over x4 clones while pure r5 clones were absent. In two
subtype B chimeric viruses (B12 and B19), r5 clones were >100-fold more abundant
than x4 or r5/x4 clones. The dual tropic C19 and C27 HIV-1 isolates outcompeted
r5 primary HIV-1 isolates, B2 and C3 in PBMCs. When AMD3100 was added or when
only U87.CD4.CCR5 cells were used, the B2 and C3 reference viruses now out
competed the r5 component of the dual tropic C19 and C27. In contrast, the same
replicative fitness was observed with dualtropic B12 and B19 HIV-1 isolates
relative to x4 HIV-1 A8 and E6 or the r5 B2 and C3 viruses, even when the r5 or
x4 component was inhibited by maraviroc (or AMD3100) or in U87.CD4.CXCR4 (or
CCR5) cells. CONCLUSIONS: In the dual tropic HIV-1 isolates, the x4 replicative
fitness is higher than r5 clones but the x4 or x4/r5 clones are typically at low
frequency in the intrapatient virus population. Ex vivo HIV propagation promotes
outgrowth of the x4 clones and provides an over-estimate of x4 dominance in
replicative fitness within dual tropic viruses.
PMID- 26435729
TI - Quality of public information matters in mate-choice copying in female zebra
finches.
AB - BACKGROUND: Mate-choice copying is a form of social learning in which an
individual gains information about potential mates by observing conspecifics.
However, it is still unknown what kind of information drives the decision of an
individual to copy the mate choice of others. Among zebra finches (Taeniopygia
guttata castanotis), only females (not males) copy the mate choice of others. We
tested female zebra finches in a binary choice test where they, first, could
choose between two males of different phenotypes: one unadorned male and one male
artificially adorned with a red feather on the forehead. After this mate-choice
test, females could observe a single unadorned male and a pair of zebra finches,
i.e. a wild-type female and her adorned mate. Pair interactions were either
restricted to acoustic and visual communication (clear glass screen between pair
mates) or acoustic communication alone (opaque screen between pair mates). After
the observation period, females could again choose between new males of the two
phenotypes in a second mate-choice test. RESULTS: In experiments with a clear
glass screen, time spent with the respective males changed between the two mate
choice tests, and females preferred adorned over unadorned males during the
second mate-choice test. In experiments with an opaque screen, time spent with
the respective males did not change between the two mate-choice tests, although
females lost an initial preference for unadorned males. CONCLUSIONS: Our results
demonstrate that the quality of the received public information (visual and
acoustic interaction of the observed pair) influences mate-choice copying in
female zebra finches.
PMID- 26435728
TI - Host sex and age influence endoparasite burdens in the gray mouse lemur.
AB - INTRODUCTION: Immunosenescence (deteriorating immune function at old age) affects
humans and laboratory animals, but little is known about immunosenescence in
natural populations despite its potential importance for population and disease
dynamics and individual fitness. Although life histories and immune system
profiles often differ between the sexes, sex-specific effects of aging on health
are rarely studied in the wild. Life history theory predicts that due to their
shorter lifespan and higher investment into reproduction at the expense of immune
defences, males might experience accelerated immunosenescence. We tested this
hypothesis by examining sex-specific age trajectories of endoparasite burden
(helminth prevalence and morphotype richness measured via fecal egg counts), an
indicator of overall health, in wild gray mouse lemurs (Microcebus murinus). To
account for potential interactions between seasonality and host sex or age we
examined the predictors of parasite burdens separately for the dry and rainy
season. RESULTS: Contrary to the prediction of immunosenescence, parasite
prevalence and morphotype richness decreased at old age in the dry season,
indicating acquired immunity by older animals. This pattern was primarily caused
by within-individual decline in parasite loads rather than the earlier mortality
of highly parasitized individuals. With the exception of an increasing cestode
prevalence in males from yearlings to prime age in the rainy season, no evidence
was found of male-biased ageing in parasite resistance. Besides this sex*age
interaction, host age was uncorrelated with rainy season parasite loads.
Seasonality did not affect the overall parasite loads but seasonal patterns were
found in the predictors of parasite prevalence and morphotype richness.
CONCLUSIONS: These results provide rare information about the age-related
patterns of health in a wild vertebrate population and suggest improvement rather
than senescence in the ability to resist helminth infections at old age. Overall,
males appear not to suffer from earlier immunosenescence relative to females.
This may partially reflect the earlier mortality of males, which can render
senescence difficult to detect. While helminth infections are not strongly
associated with survival in wild gray mouse lemurs, parasite load may, however,
reflect overall good phenotypic quality of long-lived individuals, and is a
potential correlate of fitness.
PMID- 26435730
TI - The relationship between poison frog chemical defenses and age, body size, and
sex.
AB - INTRODUCTION: Amphibians secrete a wide diversity of chemicals from skin glands
as defense against predators, parasites, and pathogens. Most defensive chemicals
are produced endogenously through biosynthesis, but poison frogs sequester
lipophilic alkaloids from dietary arthropods. Alkaloid composition varies
greatly, even among conspecific individuals collected at the same time and place,
with some individuals having only a few micrograms of one or a few alkaloids and
others possessing >1 mg of >30 alkaloids. The paucity of alkaloids in juveniles
and their abundance in adults suggests that alkaloids accumulate over time;
however, alkaloid diversity is highly variable among adult poison frogs and has
never been studied in relation to individual age. Using skeletochronology to
infer individual ages and gas chromatography-mass spectrometry and vapor phase
Fourier-transform infrared spectral analysis to identify the defensive chemicals
of 63 individuals, we tested the relationship between defensive chemicals and
age, size, and sex in the Brazilian red-belly toad, Melanophryniscus moreirae, a
poison frog that possesses both sequestered alkaloids and the biosynthesized
indolealkylamine bufotenine. RESULTS: Adult females were, on average, older and
larger than adult males. Juveniles were smaller but not necessarily younger than
adults and possessed bufotenine and 18 of the 37 alkaloids found in adults.
Alkaloid richness was positively related to age, but not size, whereas the
quantities of sequestered alkaloids and bufotenine were positively related to
size, but not age. Defensive chemicals were unrelated to sex, independent of
size. CONCLUSIONS: The relationship between alkaloid richness and age appears to
result from the gradual accumulation of alkaloids over a frog's lifetime, whereas
the relationship between the quantity of defensive chemicals and size appears to
be due to the greater storage capacity of larger individuals. The decoupling of
age and size effects increases the amount of individual variation that can occur
within a population, thereby possibly enhancing anti-predator efficacy. Further,
given that both richness and quantity contribute to the overall chemical defense
of individual frogs, our results suggest that older, larger individuals are
better defended than younger, smaller ones. These considerations underscore the
importance of including age in studies of the causes and consequences of
variation in poison frog chemical defenses.
PMID- 26435731
TI - Lung function and fractional exhaled nitric oxide among petroleum refinery
workers.
AB - BACKGROUND: Occupational and environmental exposure to petroleum refinery
products poses a great threat to human health. This study aimed to assess the
lung function and Fractional Exhaled Nitric Oxide (FeNO) among petroleum refinery
workers. METHODS: In this cross-sectional study, 112 participants (56 petroleum
refinery workers with mean age 35.20 +/- 1.62 years, and 56 age, weight, height,
ethnicity and socioeconomically matched control subjects with mean age 30.02 +/-
1.76 years) were recruited. A comprehensive clinical history and examination was
conducted to decide whether to include in the study or not. Ventilatory lung
function test parameters were recorded by using a Spirometer and Fractional
Exhaled Nitric Oxide (FeNO) was measured by Niox Mino. RESULTS: A significant
decline in lung function parameters FEV1 (p = 0.0001), FEV1/FVC Ratio (p = 0.01),
PEF (p = 0.0001), FEF 25 % (p = 0.0001), FEF-50 % (p = 0.012) was observed among
oil refinery workers compared to their matched controls. However, there was no
difference in the mean values of FeNO between the groups. CONCLUSION: Subjects
working in the petroleum refinery have significantly impaired lung functions.
However, there was no change in the values of FENO between the groups. The lung
function impairment pattern provide evidence in the favor of an obstructive lung
disease.
PMID- 26435732
TI - Biomarkers of primary open-angle glaucoma.
AB - Primary open-angle glaucoma (POAG) is a primary neuronal disease of the optic
nerve without a definable cause, and is often associated with increased
intraocular pressure. Worldwide, POAG is the second leading cause of blindness;
there are 45 million people today with POAG and bilateral blindness is present in
4.5 million of these. In order to elucidate the possible etiologic factors in
POAG, we have cataloged all known biomarkers in the aqueous humor, trabecular
meshwork, optic nerve and blood into four categories, namely extracellular matrix
(ECM), cell signaling molecules, aging/stress and immunity-related changes. We
present a theoretical model to show possible signaling pathways of the ECM, cell
signaling and innate immune response through activation of Toll-like receptor 4.
Our article suggests that ECM and innate immune biomarkers are the lead
candidates for developing the 'POAG biomarker signature'. We suggest that current
research is critical to pinpoint the causes of the disease so that new treatment
modalities can become available for better regulation of the intraocular pressure
and neuroprotection of the optic nerve.
PMID- 26435734
TI - Prediction of 1-octanol solubilities using data from the Open Notebook Science
Challenge.
AB - BACKGROUND: 1-Octanol solubility is important in a variety of applications
involving pharmacology and environmental chemistry. Current models are linear in
nature and often require foreknowledge of either melting point or aqueous
solubility. Here we extend the range of applicability of 1-octanol solubility
models by creating a random forest model that can predict 1-octanol solubilities
directly from structure. RESULTS: We created a random forest model using CDK
descriptors that has an out-of-bag (OOB) R2 value of 0.66 and an OOB mean squared
error of 0.34. The model has been deployed for general use as a Shiny
application. CONCLUSION: The 1-octanol solubility model provides reasonably
accurate predictions of the 1-octanol solubility of organic solutes directly from
structure. The model was developed under Open Notebook Science conditions which
makes it open, reproducible, and as useful as possible.Graphical abstract.
PMID- 26435733
TI - Epidemiological patterns of cervical human papillomavirus infection among women
presenting for cervical cancer screening in North-Eastern Nigeria.
AB - BACKGROUND: Sub-Saharan countries including Nigeria have the highest burden of
Human Papillomavirus (HPV) infection in the world. Most studies on HPV
surveillance in Nigeria were done in the southern part of the country.
Geographical and socio-cultural diversity of Nigeria makes these data unlikely to
be universally representative for the entire country. Northern Nigeria especially
the North-East carries a higher prevalence of cervical cancer and many of its
risk factors. The region may be harbouring a higher prevalence of HPV infection
with a possibility of different genotypic distribution. This study was carried
out to determine the burden and confirm the predominant HPV genotypes among women
presenting for cervical cancer screening at the Federal Teaching Hospital Gombe
(FTHG), North-eastern, Nigeria. METHODS: The study was an observational hospital
based cross sectional study among women who presented for cervical cancer
screening in FTHG. A total of 209 consenting women were tested for cervical HPV
infection using PCR. DNA sequencing was carried out on positive samples to
determine the prevalent HPV genotypes. RESULTS: The prevalence of cervical HPV
infection among the participants with mean age of 39.6 +/- 10.4 years was 48.1 %.
The five most predominant genotypes were 18, 16, 33, 31 and 35, with prevalence
of 44.7 %, 13.2 %, 7.9 %, 5.3 % and 5.3 % respectively. Other genotypes observed
were 38, 45, 56, 58, 82 and KC5. Multiple HPV infections were detected among 7.9
% of participants. Risk factors such as level of education (X (2) = 15.897; p =
0.007), age at sexual debut (X (2) = 6.916; p = 0.009), parity (X (2) = 23.767; p
= 0.000), number of life time sexual partners (X (2) = 7.805; p = 0.005), age at
first pregnancy (X (2) = 10.554; p = 0.005) and history of other malignancies (X
(2) = 7.325; p = 0.007) were found to have a statistically significant
association with HPV infection. CONCLUSION: This study identified a high burden
of HPV infection in Northern Nigeria while also confirming HPV 18 and 16 as the
most predominant genotypes. It further justifies the potential benefit of the
currently available HPV vaccines in the area. A larger and community based study
is however recommended for better representation of the area.
PMID- 26435735
TI - Synthesis and antibacterial activity of novel 5,6,7,8-tetrahydroimidazo[1,2
a]pyrimidine-2-carbohydrazide derivatives.
AB - BACKGROUND: The intensely increasing multi-drug resistant microbial infections
have encouraged the search for new antimicrobial agents. Hydrazone derivatives
are known to exhibit a wide variety of biological activities including anti
microbial. In heterocyclic moiety, imidazo[1,2-a]pyrimidines are the subject of
immense interest for their antimicrobial activity and also for their analgesic,
antipyretic and anti-inflammatory properties. RESULTS: Condensation of 5,6,7,8
tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide 7 with aromatic aldehydes a-k
in ethanol at reflux led to the generation of hydrazone derivatives 8a-k in 80
92% yield. The synthesis of carbohydrazide 7 was accomplished in six steps from
commercially available 2-amino pyrimidine. The structures of the synthesized
compounds were confirmed by 1H, 13C NMR, Mass and IR spectral data. All the
synthesized hydrazone derivatives 8a-k were tested in vitro for their
antibacterial activity. Compounds 8d, 8e and 8f exhibited excellent antibacterial
activity with zone of inhibition 30-33 mm against E. coli (Gram negative
bacteria) and S. aureus (Gram positive bacteria). These compounds also exhibited
excellent antibacterial activity with zone of inhibition 22-25 mm against P.
aeruginosa (Gram negative bacteria) and S. pyogenes (Gram positive bacteria).
CONCLUSION: Synthesized and recorded antibacterial activity of some new 5,6,7,8
tetrahydro-imidazo[1,2-a]pyrimidine-hydrazone derivatives.Graphical
abstract:Synthesis of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine-2-carbohydrazide
derivatives.
PMID- 26435736
TI - Diagnostic techniques in deflagration and detonation studies.
AB - Advances in experimental, high-speed techniques can be used to explore the
processes occurring within energetic materials. This review describes techniques
used to study a wide range of processes: hot-spot formation, ignition thresholds,
deflagration, sensitivity and finally the detonation process. As this is a wide
field the focus will be on small-scale experiments and quantitative studies. It
is important that such studies are linked to predictive models, which inform the
experimental design process. The stimuli range includes, thermal ignition, drop
weight, Hopkinson Bar and Plate Impact studies. Studies made with inert simulants
are also included as these are important in differentiating between reactive
response and purely mechanical behaviour.
PMID- 26435737
TI - Phytochemical composition, antiparasitic and alpha-glucosidase inhibition
activities from Pelliciera rhizophorae.
AB - BACKGROUND: Panama has an extensive mangrove area and it is one of the countries
with the highest biodiversity in America. Mangroves are widely used in
traditional medicine, nevertheless, there are very few studies that validates
their medicinal properties in America. Given the urgent need for therapeutic
options to treat several diseases of public health importance, mangrove ecosystem
could be an interesting source of new bioactive molecules. This study was
designed to evaluate the potential of Pelliciera rhizophorae as a source of
bioactive compounds. RESULTS: The present investigation was undertaken to explore
the possible antiparasitic potential and alpha-glucosidase inhibition by
compounds derived from the Panamanian mangrove Pelliciera rhizophorae. Bioassay
guided fractionation of the crude extract led to the isolation of ten chemical
compounds: alpha-amyrine (1), beta-amyrine (2), ursolic acid (3), oleanolic acid
(4), betulinic acid (5), brugierol (6) iso-brugierol (7), kaempferol (8),
quercetin (9), and quercetrin (10). The structures of these compounds were
established by spectroscopic analyses including APCI-HR-MS and NMR. Compounds 4
(IC50 = 5.3 uM), 8 (IC50 = 22.9 uM) and 10 (IC50 = 3.4 uM) showed selective
antiparasitic activity against Leishmania donovani, while compounds 1 (IC50 =
19.0 uM) and 5 (IC50 = 18.0 uM) exhibited selectivity against Tripanosoma cruzi
and Plasmodium falciparum, respectively. Moreover, compounds 1-5 inhibited alpha
glucosidase enzyme in a concentration-dependent manner with IC50 values of 1.45,
0.02, 1.08, 0.98 and 2.37 uM, respectively. Their inhibitory activity was higher
than that of antidiabetic drug acarbose (IC50 217.7 uM), used as a positive
control. Kinetic analysis established that the five compounds acted as
competitive inhibitors. Docking analysis predicted that all triterpenes bind at
the same site that acarbose in the human intestinal alpha-glucosidase (PDB:
3TOP). CONCLUSIONS: Three groups of compounds were isolated in this study
(triterpenes, flavonols and dithiolanes). Triterpenes and flavones showed
activity in at least one bioassay (antiparasitic or alpha-glucosidase). In
addition, only the pentacyclic triterpenes exhibited a competitive type of
inhibition against alpha-glucosidase.
PMID- 26435738
TI - Gold nanoparticle-labeled biosensor for rapid and sensitive detection of
bacterial pathogens.
AB - BACKGROUND: Escherichia coli O157:H7 is one of the major foodborne bacterial
pathogens and also a biodefense agent. To ensure food safety and public health,
it is very important to develop rapid methods for E. coli O157:H7 detection. In
this study, we designed a nanoparticle-labeled biosensor for the rapid detection
of E. coli O157:H7 in broth. RESULTS: Magnetic nanoparticles (MNPs) were
conjugated with monoclonal antibodies (Abs) to separate target E. coli O157:H7
cells from broth samples. Gold nanoparticles (AuNPs) were conjugated with
polyclonal Abs, and were then introduced to the MNP-target complex to form a
sandwich MNP-target-AuNP. By measuring the amount of AuNPs through an
electrochemical method, the presence and the amount of the target bacteria were
determined. Results showed a sensitivity of 10(1) colony forming units per
milliliter (cfu/ml) with a linear range of 10(1)-10(6) cfu/ml. CONCLUSIONS:
Compared to conventional culture plating methods, the biosensor reduced the
detection time from 2 to 4 days to less than 1 hour with a simple target
extraction method. The AuNP-labeled biosensor has potential applications in the
rapid detection of infectious agents for public health, biodefense, and
food/water safety.
PMID- 26435739
TI - Standards not that standard.
AB - There is a general assent on the key role of standards in Synthetic Biology. In
two consecutive letters to this journal, suggestions on the assembly methods for
the Registry of standard biological parts have been described. We fully agree
with those authors on the need of a more flexible building strategy and we
highlight in the present work two major functional challenges standardization
efforts have to deal with: the need of both universal and orthogonal behaviors.
We provide experimental data that clearly indicate that such engineering
requirements should not be taken for granted in Synthetic Biology.
PMID- 26435740
TI - Comparative evaluation of triplet antiemetic schedule versus doublet antiemetic
schedule in chemotherapy-induced emesis in head and neck cancer patients.
AB - PURPOSE: To compare the antiemetic combination of palonosetron, dexamethasone,
and aprepitant (PDA) with antiemetic combination of ondansetron and dexamethasone
(OD) in head and neck cancer patients receiving docetaxel, carboplatin, and 5-FU
based chemotherapy. METHODS: Sixty previously untreated patients were randomly
divided into two groups of thirty patients each. The PDA group received a
combination of palonosetron 0.25 mg intravenously (IV), dexamethasone 12 mg IV,
and capsule aprepitant per oral. OD group received ondansetron 16 mg IV, and
dexamethasone 12 mg IV for emesis control. The primary objective was to compare
the efficacy of two antiemetic schedules for preventing acute and delayed CINV
(chemotherapy-induced nausea and vomiting). The primary efficacy end point was
complete response (CR). RESULTS: All the patients tolerated both schedules well.
The antiemetic response for acute emesis (first 24 hours) in PDA versus OD group
was: CR was 86.7 versus 60%. For delayed emesis (from day 2-5) in PDA versus OD
group CR was 83.3 versus 53.3%. The intensity of acute nausea (first 24 hours) in
PDA versus OD group was: no nausea-70 versus 46.6%. The intensity of delayed
nausea (from day 2-5) in PDA versus OD was: no nausea-76.6 versus 43.3%. The CR
to both acute and delayed emesis (no vomiting from day 1-5) in PDA versus OD
group was 83.3 versus 53.3% (p < 0.05, significant). The CR to nausea (no nausea
from day 1-5) in PDA versus OD group was 70 versus 43.3% (p < 0.05, significant).
CONCLUSION: Although both the schedules were tolerated well, the PDA schedule
(palonosetron, aprepitant, and dexamethasone) was significantly better than the
OD schedule (ondansetron and dexamethasone) in controlling cancer CINV in the
acute as well as delayed phases.
PMID- 26435741
TI - Repurposing Drugs in Oncology (ReDO)-nitroglycerin as an anti-cancer agent.
AB - Nitroglycerin (NTG), a drug that has been in clinical use for more than a
century, has a range of actions which make it of particular interest in an
oncological setting. It is generally accepted that the main mechanism of action
of NTG is via the production of nitric oxide (NO), which improves cardiac
oxygenation via multiple mechanisms including improved blood flow (vasodilation),
decreased platelet aggregation, increased erythrocyte O2 release and decreased
mitochondrial utilization of oxygen. Its vasoactive properties mean that it has
the potential to exploit more fully the enhanced permeability and retention
effect in delivering anti-cancer drugs to tumour tissues. Moreover NTG can reduce
HIF-1alpha levels in hypoxic tumour tissues and this may have anti-angiogenic,
pro-apoptotic and anti-efflux effects. Additionally NTG may enhance anti-tumour
immunity. Pre-clinical and clinical data on these anti-cancer properties of NTG
are summarised and discussed. While there is evidence of a positive action as a
monotherapy in prostate cancer, there are mixed results in NSCLC where initially
positive results have yet to be fully replicated. Based on the evidence
presented, a case is made that further exploration of the clinical benefits that
may accrue to cancer patients is warranted. Additionally, it is proposed that NTG
may synergise with a number of other drugs, including other repurposed drugs, and
these are discussed in the supplementary material appended to this paper.
PMID- 26435744
TI - Metastatic lobular carcinoma of breast mimics primary cervix carcinoma: two case
reports and a review of the literature.
AB - Invasive lobular carcinoma (ILC) of the breast exhibits unusual
clinicopathological, radiological, histological, and metastatic patterns. We
present here two cases of ILC of the breast that presented with an unusual
pattern of metastasis involving the uterus. Our first patient presented to her
primary gynaecologist with profuse vaginal bleeding and underwent total abdominal
hysterectomy and bilateral salpingo-oophrectomy. She had fibroadenoma excised
from her left breast four years previously. Histopathology revealed lobular
carcinoma diffusely infiltrating uterus, cervix, and bilateral ovaries.
Retrospective examination of the left breast showed induration along the previous
fibroadenoma excision scar. A biopsy from the scar suggested lobular carcinoma.
Our second patient presented with a hard indurated cervix mass that mimicked
primary cervix carcinoma. She had ILC of the right breast four years previously
for which she underwent mastectomy followed by adjuvant chemotherapy and
radiotherapy. She was on tamoxifen. Further evaluation at presentation with
imaging showed extensive intra-abdominal disease involving peritoneum with
moderate ascites, adnexal masses, and confluent para-aortic nodal mass. A cervix
biopsy confirmed metastasis from lobular carcinoma. Metastatic involvement of the
genital tract should be considered in women with a history of breast cancer who
present with abnormal vaginal bleeding, suspicious pelvic examination, or
radiological findings. We suggest such patient be vigorously screened with biopsy
even if the patient is disease-free for several years. It is crucial to
differentiate the metastasis from primary carcinoma of the genital tract as there
are vast differences in the management of each.
PMID- 26435742
TI - miRNAs and resistance to EGFR-TKIs in EGFR-mutant non-small cell lung cancer:
beyond 'traditional mechanisms' of resistance.
AB - Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have
dramatically changed the prognosis of advanced non-small cell lung cancers
(NSCLCs) that harbour specific EGFR activating mutations. However, the efficacy
of an EGFR-TKI is limited by the onset of acquired resistance, usually within one
year, in virtually all treated patients. Moreover, a small percentage of EGFR
mutant NSCLCs do not respond to an EGFR-TKI, thus displaying primary resistance.
At the present time, several mechanisms of either primary and acquired resistance
have been elucidated, and new drugs are currently under preclinical and clinical
development in order to overcome resistance to treatment. Nevertheless, there
still remains much to be thoroughly investigated, as so far research has mainly
focused on the role of proteincoding genes involved in resistance to EGFR-TKIs.
On the other hand, in line with the data underscoring the relevance of non-coding
RNAs in the pathogenesis of lung cancer and modulation of response to systemic
therapies, microRNAs (miRNAs) have been supposed to play an important role in
resistance to EGFR-TKIs. The aim of this review is to briefly summarise the
existing relationship between miRNAs and resistance to EGFR-TKIs, and also
focusing on the possible clinical applications of miRNAs in reverting and
overcoming such resistance.
PMID- 26435743
TI - The clinical role of multimodality imaging in the detection of prostate cancer
recurrence after radical prostatectomy and radiation therapy: past, present, and
future.
AB - Detection of the recurrence sites in prostate cancer (PCa) patients affected by
biochemical recurrence after radical prostatectomy (RP) and radiation therapy
(RT) is still a challenge for clinicians, nuclear medicine physicians, and
radiologists. In the era of personalised and precision care, this task requires
the integration, amalgamation, and combined analysis of clinical and imaging data
from multiple sources. At present, multiparametric Magnetic Resonance Imaging
(mpMRI) and choline-positron emission tomography (PET) are giving encouraging
results; their combination allows the effective detection of local, lymph nodal,
and skeletal recurrences at low PSA levels. Future diagnostic perspectives
include the clinical implementation of PET/MRI scanners, multimodal fusion
imaging platforms for retrospective co-registration of PET and MR images, real
time transrectal ultrasound/mpMRI fusion imaging, and novel organ-specific PET
radiotracers.
PMID- 26435745
TI - The role of the implementation of policies for the prevention of exposure to
Radon in Brazil-a strategy for controlling the risk of developing lung cancer.
AB - Lung cancer is the leading cause of cancer death in the United States and other
industrialised countries. The most important risk factor is active smoking.
However, given the increased incidence of lung cancer in non-smokers, it is
necessary to improve knowledge regarding other risk factors. Radon (Rn) is a
noble gas and is the most important natural source of human exposure to ionizing
radiation. Exposure to high levels of this radioactive gas is related to an
increased risk of developing lung cancer. The objective of this work is to
highlight the importance of measuring indoor concentration of this gas and
identify which steps should be taken for achieving radiological protection. A
survey was conducted on the websites of the National Health Surveillance Agency
(ANVISA), LAMIN (Mineral Analysis Laboratory), CPRM (Geological Survey of
Brazil), Ministry of Health and PubMed. Using the words 'radon', 'lung',
'cancer', and PubMed(r), 1,371 results were obtained; when using the words
'radon', 'lung', 'cancer', and with 'Brazil' or 'Brazilians', only six results
were obtained. We emphasise that lung cancer is a major public health problem and
the exposure to Rn indoors should be considered as a risk factor for lung cancer
in non-smokers. Buildings or houses with high concentrations of Rn should be
identified. However, currently in Brazil-a country with great potential for
mineral extraction-there are no specific regulated recommendations to control
indoor exposure to Rn.
PMID- 26435746
TI - Laparoscopic extraperitoneal para-aortic lymphadenectomy.
AB - Lymph nodes are the main pathway in the spread of gynaecological malignancies,
being a well-known prognostic factor. Lymph node dissection is a complex surgical
procedure and requires surgical expertise to perform the procedure, thereby
minimising complications. In addition, lymphadenectomy has value in the
diagnosis, prognosis, and treatment of patients with gynaecologic cancer.
Therefore, a video focused on the para-aortic retroperitoneal anatomy and the
surgical technique of the extraperitoneal para-aortic lymphadenectomy is
presented.
PMID- 26435747
TI - Living better or living longer? Perceptions of patients and health care
professionals in oncology.
AB - BACKGROUND: Cancer can influence the views of patients on treatment goals and
make them different from those of health care professionals (HCPs). It is crucial
to understand patient expectations regarding cancer treatment. METHODS: We
performed a cross-sectional survey of patients with cancer and HCPs to evaluate
their perceptions about treatment priorities and to analyse variables that might
influence their opinions. To identify treatment choices, we interviewed all
participants using a structured questionnaire with fictitious case vignettes.
RESULTS: We enrolled a total of 230 participants, including 144 patients and 86
HCPs (35 nurses, 21 physicians, 30 others). Treatment priority between survival
time (28.5% for patients vs. 8.1% for HCP) and quality of life (45.8% vs. 87.2%)
differed significantly, with the remaining participants stating they were
uncertain or unwilling to respond, or providing invalid responses (P < 0.01). In
logistic regression, prioritising survival time was more frequent in patients,
adjusting for age and gender (odds ratio (OR) = 3.95; P < 0.01). The view that
the physician alone should be responsible for treatment choices was more frequent
among patients than HCPs (18.8 vs. 5.8%; P = 0.01). CONCLUSIONS: In Brazil, our
results suggest that survival time is more important for patients with cancer
than for HCPs, whereas quality of life is more important for HCPs than for
patients with cancer, who place great emphasis on physicians as decision-makers.
Given that Brazilian patients often rely on physicians for decisions, the
potential impact of different priorities between survival time and quality of
life when patients and HCPs are compared is unknown.
PMID- 26435748
TI - The Role of Molecular Imaging in Drug Delivery.
AB - The parallel development of molecular imaging and drug delivery allows the
combination of therapeutic agents with imaging moieties, which facilitates
visualisation of the drug delivery process and provides a realtime readout on the
in vivo efficacy of a therapeutic agent. Although challenging, it is feasible to
construct a highly versatile, multifunctional single 'theranostic' probe for
quantitative molecular imaging, targeted drug delivery and controlled drug
release to obtain an effective therapeutic response. Compared with conventional
methods for the evaluation of pharmacokinetics/pharmacodynamics, molecular
imaging has advantages such as substantially decreasing the workload and
increasing the volume of more precise data with statistical relevance. More
importantly, molecular imaging techniques bridge the gap between pre-clinical and
clinical research to develop candidate drugs that have the optimal target
specificity, pharmacodynamics and efficacy. With the advancement and integration
of technology in various fields, diverse types of targeted imaging probe coupled
with drug delivery potential have been developed. Preliminary data have
demonstrated that it is feasible and promising to use these targeted carriers for
simultaneous target imaging and drug delivery.
PMID- 26435749
TI - Epigenetics and the overhealing wound: the role of DNA methylation in fibrosis.
AB - Fibrosis is a progressive and potentially fatal process that can occur in
numerous organ systems. Characterised by the excessive deposition of
extracellular matrix proteins such as collagens and fibronectin, fibrosis affects
normal tissue architecture and impedes organ function. Although a considerable
amount of research has focused on the mechanisms underlying disease pathogenesis,
current therapeutic options do not directly target the pro-fibrotic process. As a
result, there is a clear unmet clinical need to develop new agents. Novel
findings implicate a role for epigenetic modifications contributing to the
progression of fibrosis by alteration of gene expression profiles. This review
will focus on DNA methylation; its association with fibroblast differentiation
and activation and the consequent buildup of fibrotic scar tissue. The potential
use of therapies that modulate this epigenetic pathway for the treatment of
fibrosis in several organ systems is also discussed.
PMID- 26435750
TI - Global DNA Methylation patterns on marsupial and devil facial tumour chromosomes.
AB - BACKGROUND: Despite DNA methylation being one of the most widely studied
epigenetic modifications in eukaryotes, only a few studies have examined the
global methylation status of marsupial chromosomes. The emergence of devil facial
tumour disease (DFTD), a clonally transmissible cancer spreading through the
Tasmanian devil population, makes it a particularly pertinent time to determine
the methylation status of marsupial and devil facial tumour chromosomes. DNA
methylation perturbations are known to play a role in genome instability in human
tumours. One of the interesting features of the devil facial tumour is its
remarkable karyotypic stability over time as only four strains with minor
karyotypic differences having been reported. The cytogenetic monitoring of devil
facial tumour (DFT) samples collected over an eight year period and detailed
molecular cytogenetic analysis performed on the different DFT strains enables
chromosome rearrangements to be correlated with methylation status as the tumour
evolves. RESULTS: We used immunofluorescent staining with an antibody to 5
methylcytosine on metaphase chromosomes prepared from fibroblast cells of three
distantly related marsupials, including the Tasmanian devil, as well as DFTD
chromosomes prepared from samples collected from different years and representing
different karyotypic strains. Staining of chromosomes from male and female
marsupial cell lines indicate species-specific differences in global methylation
patterns but with the most intense staining regions corresponding to telomeric
and/or centromeric regions of autosomes. In males, the X chromosome was
hypermethylated as was one X in females. Similarly, telomeric regions on DFTD
chromosomes and regions corresponding to material from one of the two X
chromosomes were hypermethylated. No difference in global methylation in samples
of the same strain taken in different years was observed. CONCLUSIONS: The
methylation patterns on DFTD chromosomes suggests that the hypermethylated active
X was shattered in the formation of the tumour chromosomes, with atypical areas
of methylation on DFTD chromosomes corresponding to locations of X chromosome
material from the shattered X. The incredibly stable broad methylation patterns
observed between strains and over time may reflect the overall genomic stability
of the devil facial tumour.
PMID- 26435751
TI - Neurologic injuries after primary total ankle arthroplasty: prevalence and effect
on outcomes.
AB - BACKGROUND: Neurologic injuries are complications that can arise after total
joint arthroplasty. However, no comprehensive study has been conducted on
peripheral nerve injuries after total ankle arthroplasty. The purpose of the
present study was to identify the prevalence of neurologic injury following
primary total ankle arthroplasty, the predisposing factors, and evaluate the
effect on clinical outcomes. METHODS: We retrospectively analyzed 150 consecutive
primary total ankle arthroplasty using the mobile-bearing prosthesis between
January 2005 and December 2011, in 150 patients with symptomatic ankle end-stage
arthritis. All the patients were divided into groups according to whether they
had postoperative peripheral neuropathy (23 patients) or not (127 patients). We
investigated the prevalence, predisposing factors, and effect on clinical
outcomes of neurologic injuries. The mean age was 61.3 years, and the mean follow
up period was 41.8 months. RESULTS: There were 23 nerve injuries (15.3 %),
including nine in posterior tibial nerves, six superficial peroneal nerves, six
deep peroneal nerves, one saphenous nerve, and one sural nerve. Neurologic injury
was significantly associated with the development of posttraumatic
osteoarthritis, but it was not significantly associated with other predisposing
factors, such as age, gender, body mass index, and symptom duration. Of the 23
nerve injuries, 13 (56.5 %) presented a complete, spontaneous recovery, 9 (39.1
%) presented an incomplete recovery, and 1 (4.3 %) presented no recovery. The
patients with neurologic injury had significantly lower American Orthopaedic Foot
and Ankle Society scores and lower levels of patient satisfaction. CONCLUSIONS:
The results of this study suggest that the prevalence of neurologic injury after
total ankle arthroplasty is considerable, and that neurologic injury is
associated with low levels of patient satisfaction and poor clinical outcomes at
mean of 3 years, postoperatively. Care is needed to reduce the occurrence of
neurologic injuries.
PMID- 26435752
TI - Specific detection of OCT4 isoforms in inflammatory bowel disease.
AB - BACKGROUND: Developmentally early cells are mobilized into peripheral blood in
Crohn's disease (CD) patients. OCT4, is considered to be important in sustaining
the pluripotency of stem cells. OCT4 splicing variants are differentially
expressed in pluripotent and non-pluripotent cells. Our study aims to investigate
the expression pattern of OCT4 variants and SOX-2, an essential factor implicated
in self-renewal and pluripotency, in tissue and blood samples from patients with
IBD. METHODS: Peripheral blood and tissue samples were collected from patients
with active CD and ulcerative colitis (UC), and from healthy individuals. OCT4
expression was documented by Western blot, immunohistochemistry and by reverse
transcription-real-time PCR. OCT4 isoform determination was documented using
specific primers. SOX-2 expression levels were also evaluated. RESULTS: OCT4
protein levels were significantly higher in CD tissue samples than in CD blood
samples, and in UC tissue samples. OCT4 protein was localized mainly in the
cytosol. In all samples, only the OCT4 pseudogenes and the OCT4B1 variant were
detected. OCT4B1 expression levels were elevated in both tissue and blood samples
from CD and UC cases compared to healthy controls. In CD patients only SOX-2 mRNA
levels were found slightly increased compared to healthy controls. CONCLUSION:
Our results suggest that OCT4 is expressed in patients with IBD. Furthermore, we
found the presence of the OCT4B1 isoform in IBD in both tissue and blood samples.
Our results have shown, that developmentally early cells might be mobilized into
peripheral blood as result of tissue damage, indicating a possible role of these
cells in repair of injured intestinal tract.
PMID- 26435753
TI - Differential expression of genes encoding proteins of the HGF/MET system in
insulinomas.
AB - BACKGROUND: Insulinomas are the most common functional pancreatic neuroendocrine
tumors, whereas histopathological features do not predict their biological
behaviour. In an attempt to better understand the molecular processes involved in
the tumorigenesis of islet beta cells, the present study evaluated the expression
of genes belonging to the hepatocyte growth factor and its receptor (HGF/MET)
system, namely, MET, HGF; HGFAC and ST14 (encode HGF activator and matriptase,
respectively, two serine proteases that catalyze conversion of pro-HGF to active
HGF); and SPINT1 and SPINT2 (encode serine peptidase inhibitors Kunitz type 1 and
type 2, respectively, two inhibitors of HGF activator and of matriptase).
METHODS: Quantitative real-time reverse transcriptase polymerase chain reaction
was employed to assess RNA expression of the target genes in 24 sporadic
insulinomas: 15 grade 1 (G1), six grade 2 (G2) and three hepatic metastases.
Somatic mutations of MET gene were searched by direct sequencing of exons 2, 10,
14, 16, 17 and 19. RESULTS: Overexpression of MET was observed in the three
hepatic metastases concomitantly with upregulation of the genes encoding HGF and
matriptase and downregulation of SPINT1. A positive correlation was observed
between MET RNA expression and Ki-67 proliferation index while a negative
correlation was detected between SPINT1 expression and the mitotic index. No
somatic mutations were found in MET gene. CONCLUSION: The final effect of the
increased expression of HGF, its activator (matriptase) and its specific receptor
(MET) together with a decreased expression of one potent inhibitor of matriptase
(SPINT1) is probably a contribution to tumoral progression and metastatization in
insulinomas.
PMID- 26435755
TI - Rapid morphological characterization of isolated mitochondria using Brownian
motion.
AB - Mitochondrial morphology has been associated with numerous pathologies including
cancer, diabetes, obesity and heart disease. However, the connection is poorly
understood-in part due to the difficulty of characterizing the morphology. This
impedes the use of morphology as a tool for disease detection/monitoring. Here,
we use the Brownian motion of isolated mitochondria to characterize their size
and shape in a high throughput fashion. By using treadmill exercise training,
mitochondria from heart and gastrocnemius of Balb/c mice were modulated in size
and used to investigate the protocol. Consistent with previous reports, the heart
mitochondria of untrained mice increased 5% in diameter immediately after a
single bout of moderate exercise (1.091 +/- 0.004 MUm) as compared to completely
sedentary controls (1.040 +/- 0.022 MUm). In addition, no change was observed in
the size of gastrocnemius mitochondria (1.025 +/- 0.018 MUm), which was also in
agreement with previous studies. The method was also successfully applied to
smaller Saccharomyces cerevisiae mitochondria.
PMID- 26435756
TI - Rapid vs. delayed infrared responses after ischemia reveal recruitment of
different vascular beds.
AB - Continuous infrared imaging revealed transient changes in forearm temperature
during arterial occlusion, reperfusion, and recovery in a healthy subject group.
Processing the imaging data with the k-means algorithm further revealed reactive
vascular sites in the skin with rapid or delayed temperature amplification. The
observed temporal and spatial diversity of blood-flow-derived forearm temperature
allow consideration of thermal-imaging guided placement of skin sensors to
achieve enhanced sensitivity in monitoring of skin hemodynamics.
PMID- 26435754
TI - Spotting the enemy within: Targeted silencing of foreign DNA in mammalian genomes
by the Kruppel-associated box zinc finger protein family.
AB - Tandem C2H2-type zinc finger proteins (ZFPs) constitute the largest transcription
factor family in animals. Tandem-ZFPs bind DNA in a sequence-specific manner
through arrays of multiple zinc finger domains that allow high flexibility and
specificity in target recognition. In tetrapods, a large proportion of tandem
ZFPs contain Kruppel-associated-box (KRAB) repression domains, which are able to
induce epigenetic silencing through the KAP1 corepressor. The KRAB-ZFP family
continuously amplified in tetrapods through segmental gene duplications, often
accompanied by deletions, duplications, and mutations of the zinc finger domains.
As a result, tetrapod genomes contain unique sets of KRAB-ZFP genes, consisting
of ancient and recently evolved family members. Although several hundred human
and mouse KRAB-ZFPs have been identified or predicted, the biological functions
of most KRAB-ZFP family members have gone unexplored. Furthermore, the
evolutionary forces driving the extraordinary KRAB-ZFP expansion and
diversification have remained mysterious for decades. In this review, we
highlight recent studies that associate KRAB-ZFPs with the repression of
parasitic DNA elements in the mammalian germ line and discuss the hypothesis that
the KRAB-ZFP family primarily evolved as an adaptive genomic surveillance system
against foreign DNA. Finally, we comment on the computational, genetic, and
biochemical challenges of studying KRAB-ZFPs and attempt to predict how these
challenges may be soon overcome.
PMID- 26435757
TI - Influence of restoration adjustments on prefrontal blood flow: A simplified NIRS
preliminary study.
AB - OBJECTIVE: The aim of this study was to examine, after setting several
restorations, the influence of adjusted occlusal interference during gum chewing
on blood flow in the prefrontal area as determined using near-infrared
spectroscopy. MATERIAL AND METHODS: The physiological rate was assessed using a
visual analog scale (VAS) questionnaire. We selected 16 patients who desired
prosthetic restorative treatment on the lateral dentition, and eight healthy
volunteers. Subjects were divided into three eight-person groups. One group
received restorations on the premolar area (PA), another group received
restorations on the molar area (MA), and the control group (CT) received no
prosthetic restorations. The spectroscope was fastened to the frontal region of
the head after placement of the final restoration, but before adjustment.
RESULTS: Pre-adjustment (first gum chewing for CT) blood flow in the prefrontal
cortex was measured during gum chewing. Blood flow was again measured during gum
chewing after the restoration (second gum chewing for CT) had been adjusted in
accordance with the subjective assessment of the patient while wearing the
device. The VAS provided quantification of comfort during gum chewing before and
after restoration adjustment. For the PA and MA groups, adjusting restorations
decreased discomfort significantly during gum chewing. Moreover, in the MA group,
prefrontal blood flow was significantly reduced, and blood flow correlated with
discomfort. CONCLUSIONS: Activation of the prefrontal area may provide an
objective criterion for judging the functionality of occlusion after prosthetic
occlusal reconstruction and/or orthodontics.
PMID- 26435759
TI - Man, You Might Look Like a Woman-If a Child Is Next to You.
AB - Gender categorization seems prone to a pervasive bias: Persons about whom null or
ambiguous gender information is available are more often considered male than
female. Our study assessed whether such a male-bias is present in non-binary
choice tasks and whether it can be altered by social contextual information.
Participants were asked to report their perception of an adult figure's gender in
three context conditions: (1) alone, (2) passively besides a child, or (3)
actively helping a child (n = 10 pictures each). The response options male,
female and I don't know were provided. As a result, participants attributed male
gender to most figures and rarely used the I don't know option in all conditions,
but were more likely to attribute female gender to the same adult figure if it
was shown with a child. If such social contextual information was provided in the
first rather than the second block of the experiment, subsequent female gender
attributions increased for adult figures shown alone. Additionally, female gender
attributions for actively helping relative to passive adults were made more
often. Thus, we provide strong evidence that gender categorization can be altered
by social context even if the subject of gender categorization remains identical.
PMID- 26435758
TI - Cheminformatics Research at the Unilever Centre for Molecular Science Informatics
Cambridge.
AB - The Centre for Molecular Informatics, formerly Unilever Centre for Molecular
Science Informatics (UCMSI), at the University of Cambridge is a world-leading
driving force in the field of cheminformatics. Since its opening in 2000 more
than 300 scientific articles have fundamentally changed the field of molecular
informatics. The Centre has been a key player in promoting open chemical data and
semantic access. Though mainly focussing on basic research, close collaborations
with industrial partners ensured real world feedback and access to high quality
molecular data. A variety of tools and standard protocols have been developed and
are ubiquitous in the daily practice of cheminformatics. Here, we present a
retrospective of cheminformatics research performed at the UCMSI, thereby
highlighting historical and recent trends in the field as well as indicating
future directions.
PMID- 26435760
TI - The Prediction of Students' Academic Performance With Fluid Intelligence in
Giving Special Consideration to the Contribution of Learning.
AB - The present study provides a new account of how fluid intelligence influences
academic performance. In this account a complex learning component of fluid
intelligence tests is proposed to play a major role in predicting academic
performance. A sample of 2, 277 secondary school students completed two reasoning
tests that were assumed to represent fluid intelligence and standardized math and
verbal tests assessing academic performance. The fluid intelligence data were
decomposed into a learning component that was associated with the position effect
of intelligence items and a constant component that was independent of the
position effect. Results showed that the learning component contributed
significantly more to the prediction of math and verbal performance than the
constant component. The link from the learning component to math performance was
especially strong. These results indicated that fluid intelligence, which has so
far been considered as homogeneous, could be decomposed in such a way that the
resulting components showed different properties and contributed differently to
the prediction of academic performance. Furthermore, the results were in line
with the expectation that learning was a predictor of performance in school.
PMID- 26435761
TI - Executive Resources and Item-Context Binding: Exploring the Influence of
Concurrent Inhibition, Updating, and Shifting Tasks on Context Memory.
AB - Previous research has demonstrated that context memory performance decreases as a
result of cognitive load. However, the role of specific executive resources
availability has not been specified yet. In a dual-task experiment, participants
performed three kinds of concurrent task engaging: inhibition, updating, or
shifting operations. In comparison with a no-load single-task condition, a
significant decrease in item and context memory was observed, regardless of the
kind of executive task. When executive load conditions were compared with non
specific cognitive load conditions, a significant interference effect was
observed in the case of the inhibition task. The inhibition process appears to be
an aspect of executive control, which relies on the same resource as item-context
binding does, especially when binding refers to associations retrieved from long
term memory.
PMID- 26435762
TI - Effects of Neighborhood Density on Adult Word Repetition.
AB - Presumable lexical competition has been found to result in higher perceptual
accuracy for words with few versus many neighbors. Previous studies have
typically only analyzed the lexical-semantic level, however. In order to also
explore the possibility of phonological effects, a word repetition task was
administered to 46 typical adults in which 80 stimuli differed only in
neighborhood density. In contrast to previous studies, verbal responses were
elicited in order to analyze productions holistically and segmentally at the
phonological level. An additional error analysis examined differences in
neighborhood density between target words and substitutions. Findings revealed
that words with more neighbors facilitated recognition, and were more accurately
repeated than those with fewer neighbors. When a target word was misperceived,
its substitution tended to be higher in neighborhood density, unrelated to word
frequency. In order to interpret these results, an account of lexical competition
is re-visited with consideration of characteristics of the lexicon discovered
using graph theory (Vitevitch, 2008).
PMID- 26435763
TI - Vaginal and Oral Sex Initiation Timing: A Focus on Gender and Race/Ethnicity.
AB - OBJECTIVES: Most previous studies on sexual initiation timing have examined its
effects on a variety of subsequent outcomes without first examining the
correlates and predictors of these timing categories. Studies that do exist often
do not utilize samples through young adulthood, leading to a misclassified set of
sexual timing categories. In addition, the literature does not adequately address
the issues of oral sex timing. Therefore, the objectives of this study were 1) to
explore age-cutoffs that mark the "normative" and "non-normative" entry into
vaginal and oral sex among young women and men in the U.S., creating sexual four
sexual initiation timing categories - "early," "normative," "late," and
"inexperienced," and; 2) to examine the association between race/ethnicity and
sexual initiation timing by gender. METHODS: The National Longitudinal Study of
Adolescent to Adult Health (Add Health) was used in both descriptive and
multivariate contexts to determine the net association of gender and
race/ethnicity with vaginal and oral sex initiation timing. RESULTS: Age-cutoffs
for vaginal sex timing were similar for women and men, yet differed by gender for
oral sex timing. Women were more likely than men to initiate vaginal sex (20% vs.
18%) and oral sex (19% vs. 16%) at an early age and less likely than men to
initiate these behaviors at a late age (18% vs. 19% for vaginal sex, and 15% vs.
16% for oral sex). Although most respondents initiated these two behaviors by
young adulthood, a considerable proportion remained inexperienced, with men more
likely than women to report inexperience with vaginal sex (7% vs. 5%), and women
more likely than men to report abstaining from oral sex (8% vs. 6%). Race/ethnic
differences in sexual initiation timing remained robust in the face of controls
for both women and men. CONCLUSIONS: Understanding the timing at which
adolescents and young adults transition to first vaginal and first oral sex is
critical for sex education curriculum and policy makers.
PMID- 26435764
TI - Exsolution of Fe and SrO Nanorods and Nanoparticles from Lanthanum Strontium
Ferrite La0.6Sr0.4FeO3-delta Materials by Hydrogen Reduction.
AB - Formation of uniform Fe and SrO rods as well as nanoparticles following
controlled reduction of La0.6Sr0.4FeO3-delta (LSF) and Ni-LSF samples in dry and
moist hydrogen is studied by aberration-corrected electron microscopy. Metallic
Fe and SrO precipitate from the perovskite lattice as rods of several tenths of
nm and thicknesses up to 20 nm. Based on a model of Fe whisker growth following
reduction of pure iron oxides, Fe rod exsolution from LSF proceeds via rate
limiting lattice oxygen removal. This favors the formation of single iron metal
nuclei at the perovskite surface, subsequently growing as isolated rods. The
latter is only possible upon efficient removal of reduction-induced water and,
subsequently, reduction of Fe +III/+IV to Fe(0). If water remains in the system,
no reduction or rod formation occurs. In contrast, formation of SrO rods
following reduction in dry hydrogen is a catalytic process aided by Ni particles.
It bears significant resemblance to surface diffusion-controlled carbon whisker
growth on Ni, leading to similar extrusion rods and filaments. In addition to SrO
rod growth, the exsolution of Fe nanoparticles and, subsequently, Ni-Fe alloy
particles is observed. The latter have also been observed under static hydrogen
reduction. Under strict control of the experimental parameters, the presented
data therefore open an attractive chemically driven pathway to metal
nanoarchitectures beyond the formation of "simple" nanoparticles.
PMID- 26435765
TI - A Synthetic Butenolide Diterpene is now a Natural Product Isolated from
Metaporana sericosepala, a Plant from the Madagascar Dry Forest.
AB - Antiproliferative bioassay-guided fractionation of the ethanolic extract of the
endemic Madagascan plant Metaporana sericosepala led to the first natural product
isolation of a butenolide diterpene, which was synthesized during an anti
inflammatory study in 1988. The structure of the compound was elucidated as 3
homofarnesyl-4-hydroxybutenolide (1) by analysis of its spectroscopic data,
including 1D- and 2D-NMR data and chemical evidence. The once synthetic compound
can now also be considered as a natural product. Compound 1 had modest
antiproliferative activity towards the A2780 ovarian cancer cell line,with an
IC50 value of 8 uM.
PMID- 26435766
TI - Reduction Mammoplasty: A Comparison Between Operations Performed by Plastic
Surgery and General Surgery.
AB - BACKGROUND: Reduction mammoplasty is an often-performed procedure by plastic
surgeons and increasingly by general surgeons. The question has been posed in
both general surgical literature and plastic surgical literature as to whether
this procedure should remain the domain of surgical specialists. Some general
surgeons are trained in breast reductions, whereas all plastic surgeons receive
training in this procedure. The National Surgical Quality Improvement Project
provides a unique opportunity to compare the 2 surgical specialties in an
unbiased manner in terms of preoperative comorbidities and 30-day postoperative
complications. METHODS: The National Surgical Quality Improvement Project
database was queried for the years 2005-2012. Patients were identified as having
undergone a reduction mammoplasty by Current Procedural Terminology codes.
RESULTS were refined to include only females with an International Classification
of Diseases, Ninth Revision, code of 611.1 (hypertrophy of breasts). Information
was collected regarding age, surgical specialty performing procedure, body mass
index, and other preoperative variables. The outcomes utilized were presence of
superficial surgical site infection, presence of deep surgical site infection,
presence of wound dehiscence, postoperative respiratory compromise, pulmonary
embolism, deep vein thrombosis, perioperative transfusion, operative time,
reintubation, reoperation, and length of hospital stay. RESULTS: During this time
period, there were 6239 reduction mammaplasties performed within the National
Surgical Quality Improvement Project database: 339 by general surgery and 5900 by
plastic surgery. No statistical differences were detected between the 2 groups
with regard to superficial wound infections, deep wound infections, organ space
infections, or wound dehiscence. There were no significant differences noted
between within groups with regard to systemic postoperative complications.
Patients undergoing a procedure by general surgery were more likely to experience
a failure of skin flaps, necessitating a return to the operative room (P < .05).
Operative time was longer in procedures performed by general surgery (P < .05).
CONCLUSION: Several important differences appear to exist between reduction
mammaplasties performed by general surgery and plastic surgery. A focused
training in reduction mammoplasty appears to be beneficial to the patient. The
limitations of this study include a lack of long-term follow-up with regard to
aesthetic outcome, nipple malposition, nipple sensation, and late wound sequelae.
PMID- 26435767
TI - Continuous Re-Exposure to Environmental Sound Cues During Sleep Does Not Improve
Memory for Semantically Unrelated Word Pairs.
AB - Two recent studies illustrated that cues present during encoding can enhance
recall if re-presented during sleep. This suggests an academic strategy. Such
effects have only been demonstrated with spatial learning and cue presentation
was isolated to slow wave sleep (SWS). The goal of this study was to examine
whether sounds enhance sleep-dependent consolidation of a semantic task if the
sounds are re-presented continuously during sleep. Participants encoded a list of
word pairs in the evening and recall was probed following an interval with
overnight sleep. Participants encoded the pairs with the sound of "the ocean"
from a sound machine. The first group slept with this sound; the second group
slept with a different sound ("rain"); and the third group slept with no sound.
Sleeping with sound had no impact on subsequent recall. Although a null result,
this work provides an important test of the implications of context effects on
sleep-dependent memory consolidation.
PMID- 26435768
TI - Emerging role of microRNAs in cancer stem cells: Implications in cancer therapy.
AB - A small subset of cancer cells that act as tumor initiating cells or cancer stem
cells (CSCs) maintain self-renewal and growth promoting capabilities of cancer
and are responsible for drug/treatment resistance, tumor recurrence and
metastasis. Due to their potential clinical importance, many researchers have put
their efforts over decades to unravel the molecular mechanisms that regulate CSCs
functions. MicroRNAs (miRNAs) which are 21-23 nucleotide long, endogenous non
coding RNAs, regulate gene expression through gene silencing at post
transcriptional level by binding to the 3'-untranslated regions or the open
reading frames of target genes, thereby result in target mRNA degradation or its
translational repression and serve important role in several cellular,
physiological and developmental processes. Aberrant miRNAs expression and their
implication in CSCs regulation by controlling asymmetric cell division,
drug/treatment resistance and metastasis make miRNAs a tool of great therapeutic
potential against cancer. Recent advancements on the biological complexities of
CSCs, modulation in CSCs properties by miRNA network and development of miRNA
based treatment strategies specifically targeting the CSCs as an attractive
therapeutic targets for clinical application are being critically analysed.
PMID- 26435770
TI - From cellular to chemical approach for acute neural and alternative options for
age-induced functional diseases.
AB - Endogenous "stem cell niche" (SCN) accompanying vessels contains immune system
components which in vivo determine differentiation of multi potent stem cells
toward proper cell types in given tissue. Combinations of sex steroids may
represent novel chemical approach for neuronal areas of regenerative medicine,
since they cause transformation of vascular smooth muscle stem cells into
differentiating neuronal cells. Circulating sex steroids are present during
pregnancy and can be utilized where needed, when various embryonic/fetal tissues
develop from their stem cells. Utilization of induced regeneration of tissues
(regenerative medicine) is expected being more effective in sudden failures of
younger individuals carrying intact SCN, as compared to established chronic
disorders caused by SCN alteration. An essential component of SCN are monocyte
derived cells exhibiting tissue-specific "stop effect" (SE) preventing, for
instance, an aging of neuronal cells. Its alteration causes that implantation of
neuronal stem cells will also result in their differentiation toward aging cells.
When we repair the SE by supply of circulating mononuclear cells from young
healthy individuals, we may be able to provide novel regenerative treatments of
age-induced neural diseases by sex steroid combinations. Questions regarding some
age-induced body alterations are also addressed.
PMID- 26435772
TI - Autologous tissue patch rich in stem cells created in the subcutaneous tissue.
AB - AIM: To investigate whether we could create natural autologous tissue patches in
the subcutaneous space for organ repair. METHODS: We implanted the following
three types of inert foreign bodies in the subcutaneous tissue of rats to produce
autologous tissue patches of different geometries: (1) a large-sized polyvinyl
tube (L = 25 mm, internal diameter = 7 mm) sealed at both ends by heat
application for obtaining a large flat piece of tissue patch for organ repair;
(2) a fine polyvinyl tubing (L = 25 mm, internal diameter = 3 mm) for creating
cylindrically shaped grafts for vascular or nerve repair; and (3) a slurry of
polydextran particle gel for inducing a bladder-like tissue. Implantation of
inert materials was carried out by making a small incision on one or either side
of the thoracic-lumbar region of rats. Subcutaneous pockets were created by blunt
dissection around the incision into which the inert bodies were inserted (1 or 2
per rat). The incisions were closed with silk sutures, and the animals were
allowed to recover. In case of the polydextran gel slurry 5 mL of the slurry was
injected in the subcutaneous space using an 18 gauge needle. After implanting the
foreign bodies a newly regenerated encapsulating tissue developed around the
foreign bodies. The tissues were harvested after 4-42 d of implantation and
studied by gross examination, histology, and histochemistry for organization,
vascularity, and presence of mesenchymal stem cells (MSCs) (CD271+CD34+ cells).
RESULTS: Implanting a large cylindrically shaped polyvinyl tube resulted in a
large flat sheet of tissue that could be tailored to a specific size and shape
for use as a tissue patch for repairing large organs. Implanting a smaller sized
polyvinyl tube yielded a cylindrical tissue that could be useful for repairing
nerves and blood vessels. This type of patch could be obtained in different
lengths by varying the length of the implanted tube. Implanting a suspension of
inert polydextran suspension gave rise to a bladder-like tissue that could be
potentially used for repairing heart valves. Histologically, the three different
types of tissue patches generated were organized similarly, consisting of three
layers, increasing in thickness until day 14. The inner layer in contact with the
inert material was avascular; a middle layer that was highly vascular and filled
with matrix, and an outer layer consisting of loose connective tissue. MSCs
identified as CD271+CD34+ cells were present in the medial layer and around major
blood vessels at day 4 but absent at later time points. The early-harvested
tissues, endowed with MSCs, could be used for tissue repair, while the later
harvested tissues, being less vascular but thicker and tougher, could be used as
filler tissue for cosmetic purposes. CONCLUSION: An autologous, vascularized
tissue patch of desired shape and size can be created in the subcutaneous space
by implanting different types of inert bodies.
PMID- 26435771
TI - Stem cells: An eventual treatment option for heart diseases.
AB - Stem cells are of global excitement for various diseases including heart
diseases. It is worth to understand the mechanism or role of stem cells in the
treatment of heart failure. Bone marrow derived stem cells are commonly practiced
with an aim to improve the function of the heart. The majority of studies have
been conducted with acute myocardial infarction and a few has been investigated
with the use of stem cells for treating chronic or dilated cardiomyopathy.
Heterogeneity in the treated group using stem cells has greatly emerged. Ever
increasing demand for any alternative made is of at most priority for
cardiomyopathy. Stem cells are of top priority with the current impact that has
generated among physicians. However, meticulous selection of proper source is
required since redundancy is clearly evident with the present survey. This review
focuses on the methods adopted using stem cells for heart diseases and outcomes
that are generated so far with an idea to determine the best therapeutic
possibility in order to fulfill the present demand.
PMID- 26435769
TI - Complement activation in the context of stem cells and tissue repair.
AB - The complement pathway is best known for its role in immune surveillance and
inflammation. However, its ability of opsonizing and removing not only pathogens,
but also necrotic and apoptotic cells, is a phylogenetically ancient means of
initiating tissue repair. The means and mechanisms of complement-mediated tissue
repair are discussed in this review. There is increasing evidence that complement
activation contributes to tissue repair at several levels. These range from the
chemo-attraction of stem and progenitor cells to areas of complement activation,
to increased survival of various cell types in the presence of split products of
complement, and to the production of trophic factors by cells activated by the
anaphylatoxins C3a and C5a. This repair aspect of complement biology has not
found sufficient appreciation until recently. The following will examine this
aspect of complement biology with an emphasis on the anaphylatoxins C3a and C5a.
PMID- 26435773
TI - Easily-handled method to isolate mesenchymal stem cells from coagulated human
bone marrow samples.
AB - AIM: To establish an easily-handled method to isolate mesenchymal stem cells
(MSCs) from coagulated human bone marrow samples. METHODS: Thrombin was added to
aliquots of seven heparinized human bone marrow samples to mimic marrow
coagulation. The clots were untreated, treated with urokinase or mechanically cut
into pieces before culture for MSCs. The un-coagulated samples and the clots were
also stored at 4 degrees C for 8 or 16 h before the treatment. The numbers of
colony-forming unit-fibroblast (CFU-F) in the different samples were determined.
The adherent cells from different groups were passaged and their surface profile
was analyzed with flow cytometry. Their capacities of in vitro osteogenesis and
adipogenesis were observed after the cells were exposed to specific inductive
agents. RESULTS: The average CFU-F number of urokinase-treated samples (16.85 +/-
11.77/10(6)) was comparable to that of un-coagulated control samples (20.22 +/-
10.65/10(6), P = 0.293), which was significantly higher than those of
mechanically-cut clots (6.5 +/- 5.32/10(6), P < 0.01) and untreated clots (1.95
+/- 1.86/10(6), P < 0.01). The CFU-F numbers decreased after samples were stored,
but those of control and urokinase-treated clots remained higher than the other
two groups. Consistently, the numbers of the attached cells at passage 0 were
higher in control and urokinase-treated clots than those of mechanically-cut
clots and untreated clots. The attached cells were fibroblast-like in morphology
and homogenously positive for CD44, CD73 and CD90, and negative for CD31 and
CD45. Also, they could be induced to differentiate into osteoblasts and
adipocytes in vitro. CONCLUSION: Urokinase pretreatment is an optimal strategy to
isolate MSCs from human bone marrow samples that are poorly aspirated and
clotted.
PMID- 26435774
TI - Role of computed tomography angiography in detection and staging of small bowel
carcinoid tumors.
AB - Small-bowel carcinoid tumors are the most common form (42%) of gastrointestinal
carcinoids, which by themselves comprise 70% of neuroendocrine tumors. Although
primary small bowel neoplasms are overall rare (3%-6% of all gastrointestinal
neoplasms), carcinoids still represent the second most common (20%-30%) primary
small-bowel malignancy after small bowel adenocarcinoma. Their imaging evaluation
is often challenging. State-of-the-art high-resolution multiphasic computed
tomography together with advanced postprocessing methods provides an excellent
tool for their depiction. The manifold interactive parameter choices however
require knowledge of when to use which technique. Here, we discuss the imaging
appearance and evaluation of duodenal, jejunal and ileal carcinoid tumors,
including the imaging features of the primary tumor, locoregional mesenteric
nodal metastases, and distant metastatic disease. A protocol for optimal lesion
detection is presented, including the use of computed tomography enterography,
volume acquisition, computed tomography angiography and three-dimensional
mapping. Imaging findings are illustrated with a series of challenging cases
which illustrate the spectrum of possible disease in the small bowel and
mesentery, the range of possible appearances in the bowel itself on multiphase
data and extraluminal findings such as the desmoplastic reaction in mesentery and
hypervascular liver metastases. Typical imaging pitfalls and pearls are
illustrated.
PMID- 26435776
TI - Imaging evaluation of traumatic thoracolumbar spine injuries: Radiological
review.
AB - Spine fractures account for a large portion of musculoskeletal injuries
worldwide. A classification of spine fractures is necessary in order to develop a
common language for treatment indications and outcomes. Several classification
systems have been developed based on injury anatomy or mechanisms of action, but
they have demonstrated poor reliability, have yielded little prognostic
information, and have not been widely used. For this reason, the
Arbeitsgemeinschaftfur Osteosynthesefragen (AO) committee has classified
thorocolumbar spine injuries based on the pathomorphological criteria into3 types
(A: Compression; B: Distraction; C: Axial torque and rotational deformity). Each
of these types is further divided into 3 groups and 3 subgroups reflecting
progressive scale of morphological damage and the degree of instability. Because
of its highly detailed sub classifications, the AO system has shown limited
interobserver variability. It is similar to its predecessors in that it does not
incorporate the patient's neurologic status.The need for a reliable,
reproducible, clinically relevant, prognostic classification system with an
optimal balance of ease of use and detail of injury description contributed to
the development of a new classification system, the thoracolumbar injury
classification and severity score (TLICS). The TLICS defines injury based on
three clinical characteristics: injury morphology, integrity of the posterior
ligamentous complex, and neurologic status of the patient. The severity score
offers prognostic information and is helpful in decision making about surgical vs
nonsurgical management.
PMID- 26435775
TI - Ankylosing spondylitis: A state of the art factual backbone.
AB - Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects 1% of
the general population. As one of the most severe types of spondyloarthropathy,
AS affects the spinal vertebrae and sacroiliac joints, causing debilitating pain
and loss of mobility. The goal of this review is to provide an overview of AS,
from the pathophysiological changes that occur as the disease progresses, to
genetic factors that are involved with its onset. Considering the high prevalence
in the population, and the debilitating life changes that occur as a result of
the disease, a strong emphasis is placed on the diagnostic imaging methods that
are used to detect this condition, as well as several treatment methods that
could improve the health of individuals diagnosed with AS.
PMID- 26435778
TI - Inter- and intra-rater reliability of diffusion tensor imaging parameters in the
normal pediatric spinal cord.
AB - AIM: To assess inter- and intra-rater reliability (agreement) between two region
of interest (ROI) methods in pediatric spinal cord diffusion tensor imaging
(DTI). METHODS: Inner-Field-of-View DTI data previously acquired from ten
pediatric healthy subjects (mean age = 12.10 years) was used to assess for
reliability. ROIs were drawn by two neuroradiologists on each subject data twice
within a 3-mo interval. ROIs were placed on axial B0 maps along the cervical
spine using free-hand and fixed-size ROIs. Agreement analyses for fractional
anisotropy (FA), axial diffusivity, radial diffusivity and mean diffusivity were
performed using intra-class-correlation (ICC) and Cronbach's alpha statistical
methods. RESULTS: Inter- and intra-rater agreement between the two ROI methods
showed moderate (ICC = 0.5) to strong (ICC = 0.84). There were significant
differences between raters in the number of pixels selected using free-hand ROIs
(P < 0.05). However, no significant differences were observed in DTI parameter
values. FA showed highest variability in ICC values (0.10-0.87). Cronbach's alpha
showed moderate-high values for raters and ROI methods. CONCLUSION: The study
showed that high reproducibility in spinal cord DTI can be achieved, and
demonstrated the importance of setting detailed methodology for post-processing
DTI data, specifically the placement of ROIs.
PMID- 26435777
TI - Radiation signature on exposed cells: Relevance in dose estimation.
AB - The radiation is considered as a double edged sword, as its beneficial and
detrimental effects have been demonstrated. The potential benefits are being
exploited to its maximum by adopting safe handling of radionuclide stipulated by
the regulatory agencies. While the occupational workers are monitored by
personnel monitoring devices, for general publics, it is not a regular practice.
However, it can be achieved by using biomarkers with a potential for the
radiation triage and medical management. An ideal biomarker to adopt in those
situations should be rapid, specific, sensitive, reproducible, and able to
categorize the nature of exposure and could provide a reliable dose estimation
irrespective of the time of the exposures. Since cytogenetic markers shown to
have many advantages relatively than other markers, the origins of various
chromosomal abnormalities induced by ionizing radiations along with dose-response
curves generated in the laboratory are presented. Current status of the gold
standard dicentric chromosome assay, micronucleus assay, translocation
measurement by fluorescence in-situ hybridization and an emerging protein marker
the gamma-H2AX assay are discussed with our laboratory data. With the wide choice
of methods, an appropriate assay can be employed based on the net.
PMID- 26435779
TI - Intraperitoneal tuberculous abscess: Computed tomography features.
AB - AIM: To evaluate the computed tomography (CT) features of intraperitoneal
tuberculous abscess (IPTA). METHODS: Eight patients with IPTA confirmed by
pathology were analyzed retrospectively. The clinical symptoms, medical images,
and surgical findings were evaluated. Involvement of the intestine, peritoneum,
viscera, and lymph nodes was also assessed. RESULTS: All 8 patients had a history
of abdominal discomfort for 1 to 6 mo. Physical examination revealed a palpable
abdominal mass in 6 patients. Three patients had no evidence of pulmonary
tuberculosis (TB). All IPTAs (11 abscesses) were seen as a multiseptated,
peripherally enhanced, hypodense mass with enlarged, rim-enhanced lymph nodes.
The largest abscess diameter ranged from 4.5 cm to 12.2 cm. CT showed 2 types of
IPTA: Lymph node fusion and encapsulation. Of the 8 patients, one had liver
tuberculosis and one had splenic and ovarian tuberculosis. Two cases showed
involvement of the terminal ileum and ileocecal junction. Ascites were found in 4
cases. Three patients had peritonitis and mesenteritis. Three patients showed
involvement of the omentum. Three patients had histological evidence of caseating
granuloma, and 5 had histological evidence of acid-fast bacilli. CONCLUSION: CT
is crucial in the detection and characterization of IPTA. Certain CT findings are
necessary for correct diagnosis.
PMID- 26435780
TI - Pulmonary fibrosis and emphysema: Is the emphysema type associated with the
pattern of fibrosis?
AB - AIM: To investigate whether the predominant emphysema type is associated with the
high resolution computed tomography (HRCT) pattern of fibrosis in combined
pulmonary fibrosis and emphysema (CPFE). METHODS: Fifty-three smokers with upper
lobe emphysema and lower lobe pulmonary fibrosis on - HRCT - were retrospectively
evaluated. Patients were stratified into 3 groups according to the predominant
type of emphysema: Centrilobular (CLE), paraseptal (PSE), CLE = PSE. Patients
were also stratified into 3 other groups according to the predominant type of
fibrosis on HRCT: Typical usual interstitial pneumonia (UIP), probable UIP and
nonspecific interstitial pneumonia (NSIP). HRCTs were scored at 5 predetermined
levels for the coarseness of fibrosis (Coarseness), extent of emphysema
(emphysema), extent of interstitial lung disease (TotExtILD), extent of reticular
pattern not otherwise specified (RetNOS), extent of ground glass opacity with
traction bronchiectasis (extGGOBx), extent of pure ground glass opacity and
extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion
capacity (DLCO) and systolic pulmonary arterial pressure were compared among the
groups. RESULTS: The predominant type of emphysema was strongly correlated with
the predominant type of fibrosis. The centrilobular emphysema group exhibited a
significantly higher extent of emphysema (P < 0.001) and a lower extent of
interstitial lung disease (P < 0.002), reticular pattern not otherwise specified
(P < 0.023), extent of ground glass opacity with traction bronchiectasis (P <
0.002), extent of honeycombing (P < 0.001) and coarseness of fibrosis (P < 0.001)
than the paraseptal group. The NSIP group exhibited a significantly higher extent
of emphysema (P < 0.05), total lung capacity (P < 0.01) and diffusion capacity
(DLCO) (P < 0.05) than the typical UIP group. The typical UIP group exhibited a
significantly higher extent of interstitial lung disease, extent of reticular
pattern not otherwise specified, extent of ground glass opacity with traction
bronchiectasis, extent of honeycombing and coarseness of fibrosis (0.039 > P >
0.000). Although the pulmonary arterial pressure was higher in typical UIP group
relative to the NSIP group, the difference was not statistically significant.
CONCLUSION: In CPFE patients, paraseptal emphysema is associated more with UIP
HRCT pattern and higher extent of fibrosis than centrilobular emphysema.
PMID- 26435781
TI - Development of CAD/CAM Based Brace Models for the Treatment of Patients with
Scoliosis-Classification Based Approach versus Finite Element Modelling.
AB - STUDY DESIGN: Retrospective controlled cohort study comparing the in-brace
correction of two samples of scoliosis patients with braces of different computer
aided design (CAD). PURPOSE: In-brace correction and compliance correlate with
outcome. The more standardized CAD braces that are available should enable
improved in-brace correction and outcome. This study compared recent CAD brace
developments with respect to in-brace corrections. OVERVIEW OF LITERATURE: A 2013
randomized controlled trial demonstrated that 72% of a population complying to
Scoliosis Research Society inclusion criteria on bracing did not progress using
braces (mainly Boston braces) used in the United States and Canada with moderate
corrective effect. METHODS: In-brace corrections achieved in a sample of patients
fulfilling the inclusion criteria for studies on bracing using the classification
based approach (CBA) were compared to the recent individual CAD/computer aided
manufacturing bracing based on finite element modelling approach (FEMA). RESULTS:
In-brace corrections using the different approaches differed widely. CBA in-brace
corrections were 66% of the initial value. FEMA in-brace correction was 42% of
the initial value. CONCLUSIONS: Considering the fact that in-brace correction
(and compliance) determines the end result of bracing in the treatment of
scoliosis, scoliosis braces based on CBA are superior to the FEMA and the
standard plaster based brace applications.
PMID- 26435782
TI - A Comparative Study of Lateral Lumbar Interbody Fusion and Posterior Lumbar
Interbody Fusion in Degenerative Lumbar Spondylolisthesis.
AB - STUDY DESIGN: Level 4 retrospective review. PURPOSE: To compare the radiographic
and clinical outcomes between posterior lumbar interbody fusion (PLIF) and
lateral lumbar interbody fusion (LLIF) with posterior segmental spinal
instrumentation (SSI) for degenerative lumbar spondylolisthesis. OVERVIEW OF
LITERATURE: Both PLIF and LLIF have been performed for degenerative
spondylolisthesis with good results, but no study has directly compared these two
techniques so far. METHODS: The electronic medical and radiographic records of 78
matched patients were analyzed. In one group, 39 patients underwent PLIF with SSI
at 41 levels (L3-4/L4-5), while in the other group, 39 patients underwent the
LLIF procedure at 48 levels (L3-4/L4-5). Radiological outcomes such as
restoration of disc height and neuroforaminal height, segmental lumbar lordosis,
total lumbar lordosis, incidence of endplate fracture, and subsidence were
measured. Perioperative parameters were also recorded in each group. Clinical
outcome in both groups was assessed by the short form-12, Oswestry disability
index and visual analogue scale scores. The average follow-up period was 16.1
months in the LLIF group and 21 months in the PLIF group. RESULTS: The
restoration of disc height, foraminal height, and segmental lumbar lordosis was
significantly better in the LLIF group (p<0.001). The duration of the operation
was similar in both groups, but the average blood loss was significantly lower in
the LLIF group (p<0.001). However, clinical outcome scores were similar in both
groups. CONCLUSIONS: Safe, effective interbody fusion can be achieved at multiple
levels with neuromonitoring by the lateral approach. LLIF is a viable treatment
option in patients with new onset symptoms due to degenerative spondylolisthesis
who have had previous lumbar spine surgery, and it results in improved sagittal
alignment and indirect foraminal decompression.
PMID- 26435783
TI - Prognostic Value of Preoperative Coping Strategies for Pain in Patients with
Residual Neuropathic Pain after Laminoplasty for Compressive Cervical Myelopathy.
AB - STUDY DESIGN: Single-center retrospective cohort study. PURPOSE: To clarify the
prognostic value of preoperative coping strategies for pain due to compressive
cervical myelopathy. OVERVIEW OF LITERATURE: Preoperative physical function,
imaging and electrophysiological findings are known predictors of surgical
outcomes. However, coping strategies for pain have not been considered. METHODS:
Postoperative questionnaires, concerning health-related quality of life (HRQOL)
and daily living activities, were sent to 78 patients with compressive cervical
myelopathy who had suffered from neuropathic pain before laminoplasty, and been
preoperatively assessed with respect to their physical and mental status and
coping strategies for pain. Hierarchical multiple regression analysis was
performed to clarify the extent to which the patient's preoperative coping
strategies could explain the variance in postoperative HRQOL and activity levels.
RESULTS: Forty-two patients with residual neuropathic pain after laminoplasty
were analyzed by questionnaires (28 men, 14 women; mean age, 62.7+/-10.2 years;
symptom duration, 48.0+/-66.0 months). The valid response rate was 53.8%.
Hierarchical multiple regression analysis showed that preoperative coping
strategies, which involved coping self-statements, diverting attention, and
catastrophizing, were independently associated with postoperative HRQOL and
activity level, and could explain 7% to 11% of their variance. Combinations of
the coping strategies for pain and upper/lower motor functions could explain 26%
to 36% of the variance in postoperative HRQOL and activity level. CONCLUSIONS:
Preoperative coping strategies for pain are good predictors of postoperative
HRQOL and activities of daily living in patients with postoperative residual
neuropathic pain due to compressive cervical myelopathy.
PMID- 26435784
TI - Effectiveness of Doppler Image of the Vertebral Artery as an Anatomical Landmark
for Identification of Ultrasound-Guided Target Level in Cervical Spine.
AB - STUDY DESIGN: A prospective sonographic study. PURPOSE: To verify the
effectiveness of simultaneous application of two landmarks, Doppler image of the
vertebral artery and shape of the transverse tubercle of the seventh cervical
(C7) vertebra. OVERVIEW OF LITERATURE: Counting upwards from the C7 vertebra
which only has a posterior tubercle of the transverse process is a commonly used
method for ultrasound-guided cervical nerve root block. However, each transverse
process has a different shape. METHODS: Sonograms of 20 volunteers were examined.
At first, we identified the C7 transverse process based on the presence of the
vertebral artery without the anterior tubercle. The C5 and C6 transverse
processes were identified based on the presence of anterior tubercle without the
vertebral artery. Subsequently, we placed needles on the C5, C6, and C7
transverse processes and the location and direction of needles were confirmed by
fluoroscopy. RESULTS: In the 120 segments, 93.3% of needles were placed correctly
as desired; 97.5% of needles were placed on the 5C transverse process; 97.5% of
needles were placed on the C6 transverse process; and 85.0% of needles were
placed on the C7 transverse process, respectively. Both sides showed the same
accuracy of 93.3%. CONCLUSIONS: Simultaneous application of Doppler image of the
vertebral artery and shape of the C7 transverse tubercle showed 93.3% accuracy in
identifying the target cervical level. Therefore, Doppler image of the vertebral
artery can be considered to be a useful landmark for ultrasound-guided cervical
nerve root block.
PMID- 26435785
TI - Role of the Self-Administered, Self-Reported History Questionnaire to Identify
Types of Lumbar Spinal Stenosis: A Sensitivity Analysis.
AB - STUDY DESIGN: Case-control design. PURPOSE: To evaluate the role of the self
administered, self-reported history questionnaire (SSHQ) in identifying types of
lumbar spinal stenosis (LSS). OVERVIEW OF LITERATURE: Diagnosis of types of LSS
is controversial. METHODS: A total of 235 patients with LSS were asked to respond
to the SSHQ. All of these patients recovered following surgical treatment. The
classification of LSS patients was based on history, physical examinations, and
imaging studies. It is considered to be the gold standard. Radicular and
neurogenic claudication types of LSS were based on the SSHQ developed by Konno et
al. Two categories of LSS were determined based on the SSHQ tool and gold
standard. Finally, a sensitivity analysis was carried out to evaluate the
diagnostic value of the SSHQ. RESULTS: The mean age of patients was 59.4 years.
According to the criteria for gold standard, patients were diagnosed with the
radicular type (n=103), and neurogenic claudication type (n=132). The
questionnaire had desirable sensitivity, specificity, and accuracy in
categorizing the two types of LSS: 97.8%, 66.6%, and 96.8% for the radicular
type, and 97.0%, 80.0%, and 95.7% for the neurogenic claudication type.
CONCLUSIONS: Our findings indicate that the SSHQ is a reliable and a valid
measure and it may be a clinical diagnosis support tool for identifying patients
with two types of LSS.
PMID- 26435786
TI - Prognostic Factors for Postsurgical Recovery of Deltoid Palsy due to Cervical
Disc Herniations.
AB - STUDY DESIGN: Retrospective multicenter study. PURPOSE: We aimed to investigate
prognostic factors affecting postsurgical recovery of deltoid palsy due to
cervical disc herniation (CDH). OVERVIEW OF LITERATURE: Little information is
available about prognostic factors affecting postsurgical recovery of deltoid
palsy due to CDH. METHODS: Sixty-one patients with CDH causing deltoid palsy
(less than grade 3) were included in this study: 35 soft discs and 26 hard discs.
Average duration of preoperative deltoid palsy was 11.9 weeks. Thirty-two
patients underwent single-level surgery, 22 two-level, four three-level, and
three four-level. Patients with accompanying myelopathy, shoulder diseases, or
peripheral neuropathy were excluded from the study. RESULTS: Deltoid palsy (2.4
grades vs. 4.5 grades, p<0.001) and radiculopathy (6.4 points vs. 2.1 points,
p<0.001) significantly improved after surgery. Thirty-six of 61 patients (59%)
achieved full recovery (grade 5) of deltoid palsy, with an average time of 8.4
weeks. Longer duration of preoperative deltoid palsy and more severe
radiculopathy negatively affected the degree of improvement in deltoid palsy.
Age, gender, number of surgery level, and disc type did not affect the degree of
improvement of deltoid palsy. Contrary to our expectations, severity of
preoperative deltoid palsy did not affect the degree of improvement. Due to the
shorter duration of preoperative deltoid palsy, in the context of rapid referral,
early surgical decompression resulted in significant recovery of more severe
grades (grade 0 or 1) of deltoid palsy compared to grade 2 or 3 deltoid palsy.
CONCLUSIONS: Early surgical decompression significantly improved deltoid palsy
caused by CDH, irrespective of age, gender, number of surgery level, and disc
type. However, longer duration of deltoid palsy and more severe intensity of
preoperative radiating pain were associated with less improvement of deltoid
palsy postoperatively.
PMID- 26435787
TI - Surgical Outcome for Hemodialysis-Related Upper Cervical Lesions.
AB - STUDY DESIGN: A retrospective study. PURPOSE: To investigate the surgical outcome
for hemodialysis-related upper cervical lesions. OVERVIEW OF LITERATURE: Surgical
outcome of lower cervical lesions in patients undergoing hemodialysis has been
reported. However, surgical outcome for upper cervical lesions in hemodialysis
patients is unclear. METHODS: Upper cervical lesions in nine patients undergoing
hemodialysis were surgically treated. Mean age at surgery was 61.6 years (range,
52-68 years), and the mean follow-up period was 45.4 months (range, 2-98 months).
Patients had undergone hemodialysis for an average of 25.3 years (range, 16-40
years) at surgery. Seven patients with destructive spondyloarthropathy (DSA) of
the upper cervical spine were treated with atlantoaxial or occipitocervical
fixation. Two patients with retro-odontoid pseudotumors were treated with C1
posterior arch resection alone. Japanese Orthopedic Association (JOA) scores for
cervical myelopathy, postoperative complications, postoperative radiography, and
preoperative and postoperative occipital pain were evaluated. RESULTS: Mean
preoperative and postoperative JOA score was 3.7 and 8.1, respectively. The seven
patients with DSA had severe preoperative occipital pain that disappeared
postoperatively. Postoperative radiography showed solid bone union in DSA cases
and no instability in pseudotumor cases. CONCLUSIONS: Satisfactory surgical
outcome was observed for hemodialysis-related upper cervical lesions.
PMID- 26435788
TI - Prognostic Factors of Surgical Outcome after Spinous Process-Splitting
Laminectomy for Lumbar Spinal Stenosis.
AB - STUDY DESIGN: A retrospective case review. PURPOSE: To assess the clinical and
radiographic outcomes and identify the predictive factors associated with poor
clinical outcomes after lumbar spinous process-splitting laminectomy (LSPSL) for
lumbar spinal stenosis (LSS). OVERVIEW OF LITERATURE: LSPSL is an effective
surgical treatment for LSS. Special care should be taken in patients with
degenerative lumbar scoliosis (DLS). METHODS: A consecutive retrospective case
review of patients undergoing LSPSL for LSS with a minimum 2-year follow-up was
performed. Mild DLS and mild degenerative spondylolisthesis (DS) were included in
the study. The Japanese Orthopedic Association (JOA) score and recovery rate were
reviewed. Poor clinical outcome was defined as a recovery rate <50% using
Hirabayashi's method. RESULTS: A total of 52 patients (mean age, 72 years) met
the inclusion criteria and had a mean follow-up of 2.6 years (range, 2-4.5
years). The preoperative diagnosis was LSS in 19, DS in 19, and DLS in 14 cases.
The mean JOA score significantly increased from 14.6 to 23.2 at the final follow
up. The overall mean recovery rate was 60.1%. Thirteen patients (25%) were
assigned to the poor outcome group. A higher rate of pre-existing DLS was
observed in the poor outcome (poor) group (good, 15%; poor, 62%; p=0.003) than in
the good outcome (good) group. None of the patient factors examined were
associated with a poor outcome. A progression of slippage >=5 mm was found in 8
of 24 patients (33%) in the DS group. A progression of curvature >=5 degrees was
found in 5 of 14 patients (36%) in the DLS group. The progression of scoliosis
and slippage did not influence the clinical outcome. CONCLUSIONS: The clinical
and radiographic outcomes of LSPSL for LSS were favorable. Pre-existing DLS was
significantly associated with poor clinical outcome.
PMID- 26435789
TI - Clinical and Radiological Results of Microsurgical Posterior Lumbar Interbody
Fusion and Decompression without Posterior Instrumentation for Lateral Recess
Stenosis.
AB - STUDY DESIGN: A single-center, retrospective patient review of clinical and
radiological outcomes of microsurgical posterior lumbar interbody fusion and
decompression, without posterior instrumentation, for the treatment of lateral
recess stenosis. PURPOSE: This study documented the clinical and radiological
results of microsurgical posterior lumbar interbody fusion and decompression of
the lateral recess using interbody cages without posterior instrumentation for
the treatment of lateral recess stenosis. OVERVIEW OF LITERATURE: Although
microsurgery has some advantages, various complications have been reported
following microsurgical decompression, including cage migration, pseudoarthrosis,
neurologic deficits, and persistent pain. METHODS: A total of 34 patients (13
men, 21 women), with a mean age of 56.65+/-9.1 years (range, 40-77 years)
confirmed spinal stability, and preoperative radiological findings of lateral
recess stenosis, were included in the study. Interbody polyetheretherketone cages
and auto grafts were used in all patients. Posterior instrumentation was not used
because of limited resection of the posterior lumbar structures. Preoperative and
postoperative radiographs, computed tomography scans, and magnetic resonance
imaging were assessed and compared to images taken at the final follow-up.
Functional recovery was also evaluated according to the Macnab criteria at the
final follow-up. RESULTS: The average follow-up time was 35.05+/-8.65 months
(range, 24-46 months). The clinical results, operative time, intraoperative blood
loss, and duration of hospital stay were similar to previously published results;
the fusion rate (85.2%) was decreased and the migration rate (5.8%) was
increased, compared with prior reports. CONCLUSIONS: Although microsurgery has
some advantages, migration and pseudoarthrosis remain challenges to achieving
adequate lumbar interbody fusion.
PMID- 26435790
TI - Foramen Magnum Decompression and Duraplasty is Superior to Only Foramen Magnum
Decompression in Chiari Malformation Type 1 Associated with Syringomyelia in
Adults.
AB - STUDY DESIGN: Retrospective cohort study. PURPOSE: To compare surgical results of
foramen magnum decompression with and without duraplasty in Chiari malformation
type 1 (CM-1) associated syringomyelia (SM). OVERVIEW OF LITERATURE: The optimal
surgical treatment of CM-1 associated with SM is unclear. METHODS: Twenty-five
cases of CM-1 with SM were included. There were 12 patients (48%) in the non
duraplasty group and 13 patients (52%) in the duraplasty group. The rate of
improvement, state of postoperative SM size, amount of tonsillar herniation,
preoperative symptom duration, complications and reoperation rates were analysed.
RESULTS: The rate of clinical improvement was significantly higher with
duraplasty (84.6%) than without (33.3%, p <0.05). The rate of postoperative
syrinx regression was significantly higher in the duraplasty group (84.6%) than
in the non-duraplasty group (33.3%, p <0.05). One case in the duraplasty group
needed a reoperation compared with five cases in the non-duraplasty group (p
=0.059). CONCLUSIONS: Duraplasty is superior to non-duraplasty in CM-1 associated
with SM despite a slightly higher complication rate.
PMID- 26435791
TI - Recurrent Lumbar Disc Herniation: Results of Revision Surgery and Assessment of
Factors that May Affect the Outcome. A Non-Concurrent Prospective Study.
AB - STUDY DESIGN: Non-concurrent prospective study. PURPOSE: To determine the
functional outcome after open 'fragment' discectomy for recurrent lumbar disc
herniation, and to analyze the factors that may affect the outcome. OVERVIEW OF
LITERATURE: Literature search revealed only four studies where the factors
affecting the outcome of a revision surgery for recurrent disc herniation have
been evaluated. None of these studies analyzed for diabetes, disc degeneration
and facet arthropathy. We have analyzed these features, in addition to the
demographic and clinical factors. METHODS: Thirty-four patients who underwent the
procedure were followed up for an average period of 27.1 months. The Japanese
Orthopaedic Association (JOA) score and Oswestry disability index (ODI) were used
to assess the functional outcome. Age, gender, smoking, diabetic status, duration
of recurrent symptoms, the side of leg pain, level and type of disc herniation,
degree of disc degeneration on magnetic resonance imaging, and facet joint
arthritis before first and second surgeries, were analyzed as factors affecting
the outcome. RESULTS: The average Hirabayashi improvement in JOA was 56.4%. The
mean preoperative ODI was 74.5% and the mean ODI at final follow-up was 32.2%,
the difference being statistically significant (p<0.01). Patients with diabetes,
all of whom had poor long term glycemic control, were found to have a poor
outcome in terms of ODI improvement (p=0.03). CONCLUSIONS: Open fragment
discectomy is a safe and effective surgical technique for the treatment of
recurrent disc herniation. However, patients with uncontrolled diabetes may have
a less favorable outcome.
PMID- 26435792
TI - Frequency of Vertebral Endplate Modic Changes in Patients with Unstable Lumbar
Spine and Its Effect on Surgical Outcome.
AB - STUDY DESIGN: Prospective cohort study. PURPOSE: In this study, we investigated
the frequency of vertebral endplate Modic changes (MCs) and their effects on
surgical outcomes in patients with unstable lumbar spines. OVERVIEW OF
LITERATURE: Signal changes in endplates have been classified into three types by
Modic. The prognostic role of MCs has been investigated in various spinal
disorders. METHODS: A series of 70 patients with clinical and radiographic
unstable lumbar spine were included in the study. Endplate signal intensity was
determined according to Modic classification. All patients underwent instrumented
posterolateral fusion. Functional evaluation was made using the visual analog
scale (VAS) and Oswestry disability index (ODI). RESULTS: Eighteen patients (26%)
had normal endplate intensity, 31 patients (44%) had MC type I, 20 patients (28%)
had MC type II, and one patient (1.4%) had MC type III. Pain level VAS and ODI
decreased significantly from the preoperative evaluation to the six-month and one
year postoperative evaluations. The surgical outcome (VAS and ODI) was not
significantly different between the various types of MC. CONCLUSIONS:
Posterolateral fusion is an effective treatment in patients with unstable lumbar
spines. MC do not have a significant effect on the surgical outcome of these
patients.
PMID- 26435793
TI - Evaluation of the Behavior of Spinal Deformities in Tuberculosis of the Spine in
Adults.
AB - STUDY DESIGN: A prospective clinical study. PURPOSE: The objective of the present
study was to evaluate the behavior of spinal deformities in tuberculosis (TB) of
the spine during the initial 2 years and to suggest remedial measures. OVERVIEW
OF LITERATURE: Spinal TB is the most common cause of a kyphotic deformity in many
parts of the world. Treatment of the established deformity is difficult,
hazardous and has a high complication rate. METHODS: We followed 50 adult
patients treated for spinal TB for a minimum of 2 years. Average values of
vertebral body height loss (VBL), deformity angle, kyphosis angle, and
lumbosacral joint angle at the final follow-up were compared with the values at
initial presentation. The relationship between the amount of initial VBL and
final kyphotic angle was analyzed. RESULTS: Average values of VBL, deformity
angle, kyphosis angle, and lumbosacral joint angle at initial presentation were
0.26, 12.51 degrees , 2.26 degrees , and 12.3 degrees , respectively; and the
corresponding values at the final follow-up were 0.7, 17.8 degrees , 5.64 degrees
, and 10.8 degrees , respectively. The increase was extremely significant for the
deformity angle (initial vs. 6th month, p=0.000; 6th month vs. 24th month,
p=0.000) and kyphotic angle (initial vs. 6th month, p=0.003; 6th month vs. 24th
month, p=0.000) in the thoracic and thoracolumbar regions during the first 2
years of the disease process. The increase in the deformity angle in the lumbar
region was significant only in the initial 6 months (p=0.01). We could not find
any correlation between the initial VBL and the final kyphotic angle (r=0.302,
p>0.05). CONCLUSIONS: Different regions of the vertebral column respond
differently to bony destruction caused by spinal TB. Deformity progression is
more significant during the initial 6 months of the disease process, and this may
be the best time to take remedial measures to prevent development/progression of
the deformity. Kyphotic deformity keeps increasing even after 6 months of
antituberculous treatment, and it does not correlate with the initial VBL in
adults.
PMID- 26435794
TI - Evaluation of Traumatic Spine by Magnetic Resonance Imaging and Correlation with
Neurological Recovery.
AB - STUDY DESIGN: Prospective study. PURPOSE: To compare magnetic resonance imaging
(MRI) findings with clinical profile and neurological status of the patient and
to correlate the MRI findings with neurological recovery of the patients and
predict the outcome. OVERVIEW OF LITERATURE: Previous studies have reported poor
neurological recovery in patients with cord hemorrhage, as compared to cord edema
in spine injury patients. High canal compromise, cord compression along with
higher extent of cord injury also carries poor prognostic value. METHODS:
Neurological status of patients was assessed at the time of admission and
discharge in as accordance with the American Spine Injury Association (ASIA)
impairment scale. Mean stay in hospital was 14.11+/-5.74 days. Neurological
status at admission and neurological recovery at discharge was compared with
various qualitative cord findings and quantitative parameters on MRI. In 27
patients, long-term follow-up was done at mean time of 285.9+/-43.94 days
comparing same parameters. RESULTS: Cord edema and normal cord was associated
with favorable neurological outcome. Cord contusion showed lesser neurological
recovery, as compared to cord edema. Cord hemorrhage was associated with worst
neurological status at admission and poor neurological recovery. Mean canal
compromise (MCC), mean spinal cord compression (MSCC) and lesion length values
were higher in patients presenting with ASIA A impairment scale injury and showed
decreasing trends towards ASIA E impairment scale injury. Patients showing
neurological recovery had lower mean MCC, MSCC, and lesion length, as compared to
patients showing no neurological recovery (p<0.05). CONCLUSIONS: Cord hemorrhage,
higher MCC, MSCC, and lesion length values have poor prognostic value in spine
injury patients.
PMID- 26435795
TI - The Use of T1 Sagittal Angle in Predicting Cervical Disc Degeneration.
AB - STUDY DESIGN: Retrospective evaluation. PURPOSE: To analyze the effect of T1
slope on degree of degeneration in patients with cervical disc degeneration.
OVERVIEW OF LITERATURE: The T1 slope is well known parameter that may be very
useful in evaluating sagittal balance. There are no reports on the analysis of
the relationship between T1 slope and cervical disc degeneration. We hypothesized
that T1 slope has an effect on the degree of cervical degeneration. METHODS:
Sixty patients who had cervical spine magnetic resonance imaging (MRI) in our
orthopedic clinic were enrolled. Patients were divided into two groups according
to T1 slope. Radiologic parameters obtained from radiography and cervical spine
MRI were compared between low T1 slope group (<=25) and high T1 slope group
(>25). RESULTS: Among low T1 slope group, average degeneration grade of each
cervical segment was 2.65 in C2-3, 2.50 in C3-4, 2.62 in C4-5, 3.23 in C5-6, and
2.81 in C6-7. And that of high T1 group was 2.35 in C2-3, 2.32 in C3-4, 2.59 in
C4-5, 2.79 in C5-6, and 2.32 in C6-7. Grade of degeneration of low T1 group was
significantly higher, as compared with high T1 group in C5-6 (p=0.028) and C6-7
(p=0.009). Percentage of high grade degeneration of more than grand III was 65.4%
in low T1 group and 32.4% in high T1 group (p=0.018). Risk of high grade
degeneration of C6-7 was significantly higher in low T1 group (odds ratio, 5.63;
95% confidence interval, 1.665-19.057; p=0.005). CONCLUSIONS: Patients with low
T1 slope had higher grade of degeneration regardless of age and gender. Low T1
slope is a potential risk factor of cervical spondylosis especially in the C6-7
cervical segment.
PMID- 26435796
TI - The Effect of Standing and Different Sitting Positions on Lumbar Lordosis:
Radiographic Study of 30 Healthy Volunteers.
AB - STUDY DESIGN: Radiographic review of healthy volunteers. PURPOSE: To determine
the ideal sitting positions by measuring changes in lumbar lordosis (LL) and
pelvic parameters (PPs) in various positions. OVERVIEW OF LITERATURE: Prolonged
sitting is generally accepted as an important risk factor for low back pain
(LBP). It is now recognized that spinopelvic alignment is important for
maintaining an energy-efficient posture. METHODS: Lateral spine radiographs of
thrirty healthy volunteers (male participants) were taken in standing and five
sitting positions. Radiographic measurement of LL and PPs was performed in each
position. Statistical analysis was performed to identify a correlation between
changes in the LL and PPs in each positions. RESULTS: LL in standing was 48.5
degrees +/-8.7 degrees . Sitting significantly decreased LL and segmental angle
when compared with standing (p<0.05). The lower lumbar segmental angles (L4-5 and
L5-S1) significantly decreased in all sitting positions (p<0.05), but the
decrease was relatively less on the chair with lumbar support and in the 90
degrees -angled chair. The sacral slope (SS) decreased and the pelvic tilt
increased with decreasing LL in the sitting positions. CONCLUSIONS: Sitting
causes a reduction in LL and SS when compared with standing. It might cause a
spinopelvic imbalance and result in chronic LBP. Our study showed that sitting on
a chair with back support induced minimal changes to LL. Consequently, it is
proposed that sitting on a chair with back support would be a much more ideal
position than sitting on other types of chairs.
PMID- 26435797
TI - Relative Contribution of Upper and Lower Lumbar Spinal Segments to
Flexion/Extension: Comparison between Normal Spines and Spines with Disc Disease
in Asian Patients.
AB - STUDY DESIGN: Prospective cohort study. PURPOSE: To evaluate the contribution of
upper and lower lumbar segments to flexion and extension of the lumbar spine in
normal and diseased spines. OVERVIEW OF LITERATURE: The specific contributions of
upper and lower lumbar segments during flexion/extension have rarely been
reported. Furthermore, no comparisons between the flexion/extension behaviors of
normal and diseased spines have been reported until now. METHODS: Flexion and
extension lateral radiographs of 52 adult, asymptomatic volunteers, and 67 adult
patients with lumbar spine disc disease were measured using software for total
lumbar lordosis, upper lumbar lordosis and lower lumbar lordosis and the
intervertebral angles of all segments. RESULTS: In asymptomatic volunteers, the
range of movement between flexion and extension was a mean of only 4.2 degrees
in the lower lumbar spine and a mean of 19.4 degrees in the upper lumbar spine.
In patients with disc degeneration, the range of movement between flexion and
extension was an average 6.5 degrees for lower lumbar spine and 15.6 degrees
for the upper lumbar spine. CONCLUSIONS: The results showed that upper lumbar
spine contributes more to the range of motion in flexion and extension than the
lower lumbar spine in asymptomatic individuals without lumbar disc disease, as
well as in patients with disc degeneration.
PMID- 26435798
TI - Role of Magnetic Resonance Imaging in Differentiating Spondylitis from Vertebral
Metastasis.
AB - STUDY DESIGN: Observational analytic design with a cross-sectional approach.
PURPOSE: To analyze the suitability of magnetic resonance imaging (MRI) in
distinguishing radiology images with a corresponding delineation of spondylitis
and vertebral metastasis confirmed by histology results. OVERVIEW OF LITERATURE:
MRI is an accurate modality for assessing vertebrae and their disorders.
Infections and metastasis are most commonly found in the vertebrae. It is
difficult to differentiate between these two disorders both clinically and
radiographically, particularly in atypical cases. METHODS: McNemar statistical
test was used to analyze the data. Samples were chosen using the consecutive
method. There were 35 samples (14 males and 21 females), consisting of 22 samples
of spondylitis and 13 samples of metastasis confirmed on histology examination.
RESULTS: Nineteen (86%) out of the 22 samples of histological spondylitis were
diagnosed as having spondylitis on MRI, whereas all 13 samples of metastasis were
100% accurately diagnosed on MRI. CONCLUSIONS: There was no statistically
significant difference between diagnostic radiology using MRI and histological
diagnosis with a p=0.250 (p>0.05). In this respect, MRI was more precise in
diagnosing metastasis. Typical MRI description of spondylitis was the involvement
of anterior vertebrae and components of intervertebral discs, stiffening of
discs, paravertebral abscess, and involvement of the vertebral segment sequence.
Typical MRI delineation of metastasis was involvement of the anterior posterior
vertebral component, paravertebral mass, and skip lesions.
PMID- 26435799
TI - Bilateral Pedicle and Crossed Translaminar Screws in C2.
AB - Multiple techniques exist for the fixation of C2, including axial pedicle screws
and bilateral translaminar screws. We describe a novel method of incorporating
both the translaminar and pedicle screws within C2 to improve fixation to the
subaxial spine in patients requiring posterior cervical instrumentation for
deformity correction or instability. We report three cases of patients with
cervical spinal instability, who underwent cervical spine instrumentation for
stabilization and/or deformity correction. Bilateral C2 pedicle screws were
inserted, followed by bilateral crossed laminar screws. The instrumentation
method successfully achieved fixation in all three patients. There were no
immediate postoperative complications, and hardware positioning was satisfactory.
Instrumenting C2 with translaminar and pedicle screws is technically feasible,
and it may improve fixation to the subaxial spine in patients with poor bone
quality or severe subaxial deformity, which require a stronger instrumentation
construct.
PMID- 26435800
TI - Simultaneous Use of Both Bilateral Intralaminar and Pedicle Screws for C2
Stabilization.
AB - Four patients underwent stabilization surgery using both bilateral C2 pedicle
screw (PS) and intralaminar screw (LS). Neural and vascular injury resulting from
incorrect screw placement was assessed using computed tomography (CT). The
evaluation of bone union was assessed by lateral flexion-extension X-ray films
and CT. The symptoms were improved in all patients. There were no intraoperative
complications. Furthermore, there were no cases of neurological worsening or
vascular injury from incorrect screw placement. Failure of instrumentation or
screw loosening during the follow-up period did not occur in any of the patients.
All cases had accomplished bone union at the final follow-up. Theoretically, the
stabilization technique using both bilateral C2 PS and LS at the same time can
provide more stability than any other single technique. Simultaneous use of both
bilateral C2 PS and LS is potentially a good choice for surgical repair.
PMID- 26435801
TI - Severe Spinal Injury in Hirayama Disease.
AB - Hirayama disease is a rare neurological disorder characterized by an insidious
progressive subacute unilateral or bilateral weakness of the hands and forearm
muscles leading to a painless amyotrophy. The disease primarily affects young men
in the second to third decades of life. It has always been described as a second
motor neuron disease, thus sparing the pyramidal and sensitive pathways. It
usually has a slow progression course of 3 to 5 years followed by stabilization.
Since its initial description by Keyzo Hirayama in 1959, most cases have been
reported in Asia, particularly Japan and India, although the disease reportedly
has worldwide distribution.
PMID- 26435802
TI - Lumbar Cryptococcal Osteomyelitis Mimicking Metastatic Tumor.
AB - Cryptococcus is an encapsulated, yeast-like fungus that rarely causes infection
in immunocompetent patients. We present the case report of a 66-year-old female
patient with a history of rectal cancer with an isolated lumbar vertebral
cryptococcosis proven by biopsy performed during operation. The patient was not
an immunocompromised host and did not have any other risk factors except the
history of cured rectal cancer. The presumptive diagnosis based on imaging
studies was metastatic spine cancer, so operation was performed. However,
cryptococcal osteomyelitis was diagnosed in the pathologic examination. This case
report emphasizes that we should be aware that lumbar cryptococcosis can be a
rare cause of mimicking lesions with metastatic cancer.
PMID- 26435803
TI - Iatrogenic Lumbar Vertebral Fracture during Osteosynthesis for a Trochanteric
Fracture of the Femur in Diffuse Idiopathic Skeletal Hyperostosis.
AB - Vertebral fractures occur with only slight trauma in patients with diffuse
idiopathic skeletal hyperostosis (DISH). However, a lumbar vertebra fracture, due
to an intraoperative body position has not been previously reported. An 87-year
old woman with kyphosis sustained a left trochanteric fracture of her femur. The
patient was placed in a supine position during the operation. Postoperatively,
the patient experienced severe right thigh pain. Magnetic resonance imaging
revealed an L4 vertebral fracture. Computed tomography revealed ankylosis from
the upper thoracic spine to the sacrum. While in a supine position under general
anesthesia, the contact of the patient's lower back with operating table likely
created a fulcrum at her lumbosacral spine acting as a long lever arm, bearing
the mass of her upper body. We performed L1-S2 posterior stabilization. DISH
patients with kyphosis placed in a supine position have an increased risk for
lumbar vertebral fracture.
PMID- 26435804
TI - Adjacent Segment Pathology after Lumbar Spinal Fusion.
AB - One of the major clinical issues encountered after lumbar spinal fusion is the
development of adjacent segment pathology (ASP) caused by increased mechanical
stress at adjacent segments, and resulting in various radiographic changes and
clinical symptoms. This condition may require surgical intervention. The
incidence of ASP varies with both the definition and methodology adopted in
individual studies; various risk factors for this condition have been identified,
although a significant controversy still exists regarding their significance.
Motion-preserving devices have been developed, and some studies have shown their
efficacy of preventing ASP. Surgeons should be aware of the risk factors of ASP
when planning a surgery, and accordingly counsel their patients preoperatively.
PMID- 26435806
TI - Erector Spinae Tubercular Abscess.
PMID- 26435805
TI - Lumbar Stenosis: A Recent Update by Review of Literature.
AB - Degeneration of the intervertebral disc results in initial relative instability,
hypermobility, and hypertrophy of the facet joints, particularly at the superior
articular process. This finally leads to a reduction of the spinal canal
dimensions and compression of the neural elements, which can result in neurogenic
intermittent claudication caused by venous congestion and arterial hypertension
around nerve roots. Most patients with symptomatic lumbar stenosis had neurogenic
intermittent claudication with the risk of a fall. However, although the physical
findings and clinical symptoms in lumbar stenosis are not acute, the radiographic
findings are comparatively severe. Magnetic resonance imaging is a noninvasive
and good method for evaluation of lumbar stenosis. Though there are very few
studies pertaining to the natural progression of lumbar spinal stenosis, symptoms
of spinal stenosis usually respond favorably to non-operative management. In
patients who fail to respond to non-operative management, surgical treatments
such as decompression or decompression with spinal fusion are required.
Restoration of a normal pelvic tilt after lumbar fusion correlates to a good
clinical outcome.
PMID- 26435807
TI - Author Response: Isolated Spontaneous Primary Tubercular Erector Spinae Abscess:
A Case Report and Review of Literature.
PMID- 26435809
TI - Barrier Factors to the Completion of Diabetes Education in Korean Diabetic Adult
Patients: Korea National Health and Nutrition Examination Surveys 2007-2012.
AB - BACKGROUND: Diabetes is a disease with high social burdens and is expected to
increase gradually. A long-term management is essential for the treatment of
diabetes, requiring patient self-cares. Diabetes education is important for such
self-cares, but it does not sufficiently take place. In addition, little studies
have been conducted on the barriers to the completion of diabetes education. This
study, thus, aimed to analyze the factors related to the completion of diabetes
education and investigate its barriers. METHODS: Of 50,405 respondents to the
fourth and fifth Korea National Health and Nutrition Examination Survey, a total
of 3,820 were selected for the analysis, excluding those aged 29 or younger and
those with missing values. The completion of diabetes education was set as a
dependent variable and an analysis was made on the factors that affect the
dependent variable. A multivariable logistic regression was employed for the
analysis. RESULTS: Lower educational level was associated with less diabetes
education, and the degree of diabetes education was lower in the group with male,
the group that didn't have a family history or was not aware of a family history,
the group that was not currently aware of diabetes and the group without a
spouse. There was no difference in the completion of diabetes education by
underlying diseases, family income level, age, residing area, economic activity
status, insurance coverage, smoking, and drinking. CONCLUSION: Diabetes education
is of importance for the treatment and management of diabetes. Currently,
however, diabetes education is not sufficiently carried out in Korea. The
completion rate of diabetes education was low in male, patients without or not
knowing a family history, patients who were not currently aware of their
diabetes, patients without a spouse, and patients with low educational level.
Therefore, encouraging these patients to take the education will be a more
effective approach to increase the completion rate of diabetes education.
PMID- 26435808
TI - An Overview and Update of Chronic Myeloid Leukemia for Primary Care Physicians.
AB - Chronic myeloid leukemia (CML) accounts for approximately 15% of adult leukemias.
Forty percent of patients with CML are asymptomatic, in whom the disease is
detected solely based on laboratory abnormalities. Since the introduction of
tyrosine kinase inhibitor therapy in 2001, CML has become a chronic disease for
the majority of patients. Primary care physicians may be the first to recognize a
new diagnosis of CML. In patients with known CML, the primary care physician may
be the first to detect disease progression or adverse effects to therapy. This
article provides an overview of the clinical presentation, diagnostic approach,
and treatment considerations of CML.
PMID- 26435810
TI - Perceived Stress, Alexithymia, and Psychological Health as Predictors of Sedative
Abuse.
AB - BACKGROUND: The harmful effects of sedative medications and substances in
conjunction with limited research regarding predictive psychological constructs
of drug abuse necessitate further investigation of associated factors. Therefore,
the present study aimed to elucidate the roles of perceived stress, alexithymia,
and psychological health as predictors of sedative abuse in medical students.
METHODS: In this cross-sectional study, 548 students at Kermanshah University of
Medical Sciences, Iran, were selected using stratified random sampling. The data
were obtained using the Perceived Stress Scale, an alexithymia scale (Farsi
version of the Toronto Alexithymia Scale-20), and a General Health Questionnaire
to assess psychological health. Data were analyzed using discriminant analyses.
RESULTS: The results demonstrated that the user and non-user of sedative
substances groups had significantly different predictive variables (except for
social function disorder) (P>0.05). Physical complaints, alexithymia, and
perceived stress, which had standard coefficients of 0.80, 0.60, and -0.27,
respectively, predicted sedative drug use. CONCLUSION: The results of the present
study indicate that perceived stress, alexithymia, physical complaints, anxiety,
and depression are associated with sedative drug abuse.
PMID- 26435811
TI - Breast Feeding Is Associated with Postmenopausal Bone Loss: Findings from the
Korea National Health and Nutrition Examination Survey.
AB - BACKGROUND: Postmenopausal osteoporosis is a common disease which can cause
various morbidity and economic burden. Lactation is known to cause a decline in
bone mineral density (BMD), but there are controversies on whether decreased BMD
is fully recovered after lactation and whether lactation duration has an
influence on postmenopausal BMD. This study was conducted to see whether
breastfeeding is associated with postmenopausal bone loss using a highly
representative sample of Korean population. METHODS: Retrospective cross
sectional study was done using data collected from Korea National Health and
Nutrition Examination Survey V. The study outcome was BMD measured with dual
energy X-ray absorptiometry and divided into 2 groups: normal or low BMD (T
score<-1), and breastfeeding duration was categorized into 4 groups (never, 1st,
2nd, and 3rd tertile). Logistic regression analysis was done to examine the
association between lactation duration and BMD. RESULTS: Among 1,694
postmenopausal women (mean age, 63.5+/-9.1), 85.71% were in low BMD group.
Compared to never breastfeeding group, postmenopausal women with longer than 79
months of breastfeeding duration are more likely to have low BMD (adjusted risk
ratio [ARR]=1.24; 95% confidence interval, 1.17 to 1.32). As the duration of
breastfeeding increases, ARR and risk difference for low BMD also increases (P
for trend=0.008). CONCLUSION: The study results showed that total breastfeeding
duration was associated with postmenopausal low BMD. All women planning on
breastfeeding should be aware of its risks and should take adequate dietary
calcium and vitamin D before, during, and after breastfeeding.
PMID- 26435812
TI - Time to First Cigarette and Hypertension in Korean Male Smokers.
AB - BACKGROUND: Morning blood pressure surge affects to cardiovascular disease risk.
Short time to first cigarette (TTFC) after waking can enhance morning blood
pressure surge, and accelerate atherosclerosis. METHODS: We investigated that the
relationship between TTFC and blood pressure. The study subjects included male
current smokers (n=211) who had health check-up in Hallym University Sacred Heart
Hospital from July to September, 2014. We categorized the subjects into 2 groups
according to TTFC; early TTFC (TTFC <30 minutes) and late TTFC (TTFC >=30
minutes), and the subjects who were taking antihypertensive medications or had a
high blood pressure (>140 mm Hg or 90 mm Hg) were defined as hypertensive group.
Multivariate logistic regression was performed to estimate the odds ratio and 95%
confidence interval to investigate the association between TTFC and hypertensive
group. RESULTS: Compared with late TTFC, early TTFC had higher odds (odds ratio
[OR], 3.87; 95% confidence interval [CI], 1.89-7.94) for hypertensive group.
After adjusting confounding factors, early TTFC was significantly associated with
an increased risk of hypertension (OR, 4.43; 95% CI, 1.84-10.70). CONCLUSION:
early TTFC after waking is associated with hypertension. It suggests delaying
TTFC might help to control of blood pressure among the current smokers who are
not ready to immediately quit smoking.
PMID- 26435813
TI - Association between Helicobacter pylori Infection and Cerebral Small Vessel
Disease.
AB - BACKGROUND: Small vessel disease is an important cause of cerebrovascular
diseases and cognitive impairment in the elderly. There have been conflicting
results regarding the relationship between Helicobacter pylori infection and
ischemic stroke. This study aimed to examine the association between H. pylori
infection and cerebral small vessel disease. METHODS: The study included 1,117
patients who underwent brain magnetic resonance imaging and H. pylori
identification between 2005 and 2013 at Health Promotion Center, Seoul National
University Hospital. Multivariable logistic regression analysis was used to
assess the association between H. pylori infection and small vessel disease with
adjustment for age, sex, hypertension, diabetes mellitus, dyslipidemia, body mass
index, smoking status, problem drinking, and antiplatelet use. RESULTS: The
adjusted odds ratios (aORs) for the association between H. pylori infection and
silent brain infarction and cerebral microbleeds were 1.03 (95% confidence
interval [CI], 0.66-1.61) and 0.70 (95% CI, 0.38-1.28), respectively. The aORs
for silent brain infarction and cerebral microbleeds were 0.81 (95% CI, 0.44
1.44) and 0.59 (95% CI, 0.30-1.18) in patients aged <65 years and 1.59 (95% CI,
0.78-3.22) and 1.89 (95% CI, 0.38-9.33) in those aged >65 years, respectively.
Moreover, the aORs for silent brain infarction and cerebral microbleeds were 0.96
(95% CI, 0.54-1.71) and 0.74 (95% CI, 0.33-1.69) in H. pylori-infected patients
without atrophic gastritis and 0.89 (95% CI, 0.48-1.62) and 0.99 (95% CI, 0.43
2.27) in those with atrophic gastritis, respectively. CONCLUSION: No association
between H. pylori infection and small vessel disease was observed. H. pylori
induced inflammation may not be a risk factor for microcirculatory damage in the
brain.
PMID- 26435814
TI - Clinical Characteristics and Metabolic Health Status of Obese Korean Children and
Adolescents.
AB - BACKGROUND: This study aimed to determine the prevalence of metabolically healthy
and unhealthy obesity (MHO and MUO, respectively) and examine the demographic,
anthropometric, and lifestyle predictors of metabolic health status in Korean
children and adolescents. METHODS: This study was based on data collected from
the Korean Children-Adolescent Study in 2010. A total of 1,700 children (846 boys
and 854 girls) were included in the primary cohort and classified into
metabolically healthy and unhealthy groups according to factors related to the
metabolic syndrome. Demographic and biochemical features were evaluated in study
participants. Logistic regression estimated the odds ratios of having more fat
mass among MUO compared with MHO children after adjusting for confounding
factors. RESULTS: Mean body mass index was higher in the MUO group than in the
MHO group (24.83 vs. 23.02 kg/m(2), respectively). The proportion of obese
participants was also higher in the MUO group (59.4%) than in the MHO group
(20.7%). MHO children were more likely to have parents with better socioeconomic
status and a higher fruit and vegetable intake compared with MUO children. Higher
fat mass and percent fat was associated with MUO according to multiple logistic
regression analysis. CONCLUSION: Fat mass and percent fat are associated with
metabolically healthy phenotypes of obesity among children and adolescents.
PMID- 26435815
TI - Helicobacter pylori: A Possible Risk Factor for Bone Health.
AB - BACKGROUND: Helicobacter pylori (H. pylori) infection may cause systemic
inflammation and increase the production of tumor necrosis factor-alpha,
interleukin-1, and interleukin-6. Unfortunately, bone mineral density also may be
affected by these cytokines. This study aimed to evaluate the association between
bone mineral density and H. pylori infection. METHODS: A cross-sectional study
evaluated 1,126 men undergoing a comprehensive health screening in a private
Korean screening center. Subjects' sera were tested for H. pylori antibodies
(immunoglobulin G) using an enzyme-linked immunosorbent assay, and bone mineral
densities (g/cm(2)) of the lumbar spine, femoral neck, and total femur were
obtained using dual-energy X-ray absorptiometry. To evaluate the difference in
bone mineral density according to H. pylori infection status, the adjusted mean
bone mineral densities at each site were compared after adjusting for potential
confounders, including age, sex, body mass index, smoking, alcohol consumption,
and exercise. RESULTS: H. pylori infection was associated with a significant
decrease in mean lumbar bone mineral density (H. pylori-positive, 1.190 g/cm(2);
H. pylori-negative, 1.219 g/cm(2); P=0.006), which was greatest among men who
were >=50 years old (H. pylori-positive, 1.193 g/cm(2); H. pylori-negative, 1.233
g/cm(2); P=0.006). However, no significant association was observed in the bone
mineral densities of the total femur and femoral neck. CONCLUSION: In men, H.
pylori infection was negatively associated with lumbar bone mineral density. This
association may be useful in the early detection, prevention, and management of
male osteoporosis.
PMID- 26435817
TI - Incidence of Type 2 Diabetes Mellitus among Emirati Residents in Ajman, United
Arab Emirates.
AB - BACKGROUND: Diabetes mellitus (DM), particularly type-2 is a major public health
concern worldwide. Not much information is available with regard to the incidence
of DM in United Arab Emirates (UAE). This study aimed at determining the
incidence rate of diabetes mellitus among Emirati population in Ajman, UAE. This
is a retrospective cohort study. METHODS: This study was conducted in all primary
health care centers and Shaikh Khalifa and GMC Hospitals, Ajman, UAE where the
Emirati population primarily go for diagnosis and treatment. The incident cases
of diabetes mellitus were collected during the period 2010 January to December.
RESULTS: A total of 158 cases newly detected in 2010, 54 were among non-Emiratis
and one was type-1 diabetes. Eliminating these, the remaining 101 were included
in the analysis. The age of the patients ranged from 23 years to 78 years; 35
(34.7%) males and 66 (65.3%) were females. The overall incidence observed was
4.8/1,000 person-years (PY) with a female predominance of 6.3/1,000 PY against
incidence among males of 3.3/1,000 PY. With regard to age specific incidence rate
among males, it increases with age till 60 years and then showed a decreasing
trend. Among females also the same trend was observed but not as similar to
males. CONCLUSION: The highest incidence rate was observed in the 55-59 age group
among males, 23.4/1,000 PY and females, 32.4/1,000 PY. Among males the incidence
rate was much less compared to females in-the age groups older than 59 years.
PMID- 26435818
TI - Comments on Statistical Issues in September 2015.
PMID- 26435816
TI - Dietary Fat Intake and the Risk of Metabolic Syndrome in Korean Adults.
AB - BACKGROUND: The effect of dietary fat intake on the risk of cardiovascular
disease remains unclear. We investigated the association between dietary fat and
specific types of fat intake and the risk of metabolic syndrome. METHODS: The
study population included 1,662 healthy adults who were 50.2 years of age and had
no known hypertension, diabetes, hyperlipidemia, or metabolic syndrome at the
initial visit. Dietary intake was obtained from a 1-day food record. During 20.7
months of follow-up, we documented 147 cases of metabolic syndrome confirmed by
self-report, anthropometric data, and blood test results. The intakes of total
fat, vegetable fat, animal fat, saturated fatty acid (SFA), polyunsaturated fatty
acid (PUFA), monounsaturated fatty acid (MUFA), and cholesterol level divided by
quintile. Multivariate analyses included age, sex, body mass index, smoking
status, alcohol intake, physical activity, total calorie, and protein intake.
RESULTS: Vegetable fat intake was inversely associated with metabolic syndrome
risk (odds ratio for the highest vs. the lowest quintile, 0.33; 95% confidence
interval, 0.14 to 0.76). Total fat, animal fat, SFA, PUFA, MUFA, and cholesterol
intakes showed no association with metabolic syndrome. Vegetable fat intake was
inversely associated with the risk of hypertriglyceridemia among the components
of metabolic syndrome. CONCLUSION: These data support an inverse association
between vegetable fat and the risk of metabolic syndrome.
PMID- 26435819
TI - Tuberculosis in Chronic Obstructive Pulmonary Disease.
PMID- 26435820
TI - Preventive effect of Malva on urinary toxicity after radiation therapy in
prostate cancer patients: A multi-centric, double-blind, randomized clinical
trial.
AB - BACKGROUND: For patients receiving external beam radiation therapy (EBRT) after
radical prostatectomy as adjuvant treatment or patients receiving EBRT as
definitive treatment, partial irradiation of the urinary bladder is common. Many
of such patients experience some degree of radiation-induced cystitis during or
after EBRT. There is currently no efficient treatment for preventing radiation
cystitis. OBJECTIVE: The aim of this study was to evaluate the effectiveness of
one of the safe mucilaginous herbs (Malva) in preventing radiation-induced
dysuria in patients who are undergoing EBRT for prostate cancer. METHODS: From
April 2013 to August 2014, 68 patients were randomized into two groups using four
block randomization, 34 to the drug (Malva) group and 34 to the placebo group. Of
the 68 patients who began the study, 60 completed it. They were instructed to use
the medication, i.e., Malva or the placebo, three times a day for six weeks. They
were followed by a physician every two weeks for eight weeks, and urinary
function was assessed in each visit by asking questions based on the Visual
Prostate Symptom Score (VPSS) and a dysuria severity score. The changes in the
VPSS and dysuria severity score between baseline and each follow-up visit were
compared between the two groups in the study using repeated measures analysis of
variance (ANOVA) and t-tests. RESULTS: The median age of the 68 patients was 66.
Twenty-one of 27 patients in the control group (77.7%) suffered from dysuria,
while dysuria was detected in 23 of 33 patients (69.6%) who received Malva (odds
ratio=2.70 for dysuria). After two weeks, four weeks, and six weeks of treatment
with Malva, dysuria due to EBRT was milder in the treatment group than in the
control group, and the differences were statistically significant (p = 0.005, p =
0.004, p = 0.001, respectively). CONCLUSION: To the best of our knowledge, our
study is the first study to assess the protective effect of a mucilaginous herb
(Malva) against urinary toxicity induced by EBRT. The positive results of this
study warrant further studies in this field.
PMID- 26435821
TI - Detection of Rotavirus in children with acute gastroenteritis in Zagazig
University Hospitals in Egypt.
AB - INTRODUCTION: Rotavirus is the major cause of acute gastroenteritis (AGE) in
infants and young children all over the world. The objective of the study was to
compare different methods for detecting rotavirus and to assess the burden of
rotavirus as a causative agent for AGE in children younger than five. METHODS:
This case control study included 65 children with AGE and 35 healthy control
children. They were chosen from the Pediatric Department of Zagazig University
Hospitals from October 2014 to March 2015. Stool samples were obtained and
assayed for rotavirus by the immunochromatography test (ICT), enzyme linked
immunosorbent assay (ELISA) and quantitative real time RT-PCR (qr RT-PCR).
RESULTS: Fifty out of the 65 patients (76.9%) were positive for qr RT-PCR. Forty
five (69.2%) and 44 (67.7%) were positive for ICT and ELISA, respectively. There
was a significant association between the severity of the disease as determined
by the Vesikari score and rotavirus infection. CONCLUSION: This study
demonstrated that ICT is a useful method for the rapid screening of group A
rotavirus in fecal specimens, because it is rapid, inexpensive, easy to perform,
and requires very little equipment. In addition, this study highlights the
substantial health burden of rotavirus AGE among children less than five.
PMID- 26435822
TI - First report of death due to Hemiscorpius acanthocercus envenomation in Iran:
Case report.
AB - Scorpion stings are significant causes of death in the western and southern
regions of Iran. To date, reports have indicated that the H. lepturus species is
the main cause of mortality due to scorpion stings. One of the species that
belongs to this genus is Hemiscorpius acanthocercus (H. acanthocercus). This
scorpion's venom is cytotoxic, and it causes pathological changes in the blood
and can cause severe damage to the kidneys. The pain of Hemiscorpius' sting is
mild and asymptomatic in the early hours. Delays in the treatment of these
victims can cause hemolysis, hematuria, kidney failure, and even death. In this
paper, we report the first known death due to an H. acanthocercus' sting in Iran.
PMID- 26435823
TI - Post-traumatic growth: a qualitative analysis of experiences regarding positive
psychological changes among Iranian women with breast cancer.
AB - INTRODUCTION: Cancer diagnosis is an extremely stressful experience that has a
profound impact on a patient's life. Cancer related perceived stress and
complications may lead to the experience of positive psychological changes and
post-traumatic growth (PTG). Since there is lack of qualitative research
assessing the experience of PTG in Iranian women with breast cancer, this study
aims to investigate experiences relating to PTG of Iranian women. METHODS: A
qualitative phenomenological approach was selected to explore the experiences of
Iranian women with PTG. Data were gathered using semi-structured, in-depth
interviews with 18 eligible patients, which were then transcribed and analyzed
using Van Manen's thematic analysis approach. Data gathering and analyses were
conducted simultaneously. In addition, MAXQDA software was used for data
management. RESULTS: In this study, the participants were 18 Iranian women
between the ages of 31 and 65 years. Four prominent themes were extracted from
the participant's statements that demonstrated the Iranian women's experiences
with breast cancer-induced psychological growth and maturity: 1) appreciate of
life, 2) stability, 3) spiritual prosperity, and 4) effective interaction.
CONCLUSION: Health care professionals are strongly recommended to design robust
and timely intervention programs to improving PTG among breast cancer survivors
and reduce their perceived distress resulting from cancer diagnosis.
PMID- 26435824
TI - Prediction of trauma-specific death rates of pedestrians of Fars Province, Iran.
AB - INTRODUCTION: Pedestrians are the most vulnerable group to accidents among road
users. Due to the well-known concerns and complications of accidents involving
pedestrians, the aim of this study was to identify the rate of such accidents for
five-year period. METHODS: We analyzed all fatalities among pedestrians caused by
traffic accidents during years of 2009-2013 in Fars Province in Iran. The study
was a cross-sectional study in which logistic regression analysis was used to
predict the death rate among pedestrians. Sensitivity analysis using the Monte
Carlo method was used to increase the accuracy of the results. Then, we predicted
the death rates for the years 2014-2018 predicted and compared the results with
the actual data from the previous five-year period (2009-2013). RESULTS: During
2009-2013, 1723 out of 8689 (20.3%) of the people killed in traffic accidents
were pedestrians. The death rate for male pedestrians in 2011 was estimated to be
10.86 per 100,000 (with an uncertainty interval of 95% giving a range of 9.85
12.05 per 100,000). Compared to the data for 2006, this represented a decrease of
20% (with a mean decrease of 4% per year). Based on these data, the death date in
2018n was projected to be 8.08 per 100,000 (with an uncertainty interval of 95%
giving a range of 7.26-8.87). Similar data and analysis for women indicated that
the reduction in the rate of fatalities has been smaller than that for men in
recent years, i.e., 2.2% versus 4%. CONCLUSION: Although great progress has been
made in reducing traffic accidents, to date, the death rate is still high among
pedestrians. It is essential to continue to find ways to reduce traffic accidents
and the pedestrians' deaths associated with them, especially among the elderly,
who make up a disproportionate fraction of the deaths.
PMID- 26435825
TI - Probiotic for irritable bowel syndrome in pediatric patients: a randomized
controlled clinical trial.
AB - BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder
in children. Recently, probiotics have been suggested as a treatment option for
gastrointestinal disorders. The most effective species and the most appropriate
doses are still unknown. OBJECTIVE: The aim of this study was to assess the
effects of Lactobacillus GG (LGG) for treating IBS in pediatric patients.
METHODS: In a controlled, double blind, randomized trial, patients with IBS
diagnosed by Rome III criteria from August 2012 to September 2012 at Dr. Sheikh
Hospital, Mashhad University of Medical Sciences, Iran, were assigned to one of
two groups, i.e., intervention and control groups. For four weeks, the
intervention group received a probiotic in capsule form that contained LGG at a
concentration of 1*10(10) cfu/ml bacteria. For the same period, the control group
received a placebo capsule that had the same shape and color but only contained
inulin, which also was present in the LGG capsules. The primary outcome was any
change in the severity of the patients' pain, and we used a five-point Likert
scale to evaluate the severity of their pain. Secondary outcomes were ghanges of
the functional scale, stool patterns, and associated problems. RESULTS: Fifty-two
patients participated in the study, and 26 patients were assigned randomly to
each of the two groups. The severity of the patients' pain decreased
significantly in the intervention group after one, two, three, and four weeks of
treatment, as indicated by P-values of 0.01, 0.00, 0.00, and 0.00, respectively.
Also, there was significant improvement in the functional scale after two weeks
of treatment (P-value <= 0.00). CONCLUSION: Lactobacillus GG at a concentration
of 1*10(10) cfu/ml for a period of four weeks can lessen the severity of the
patients' pain and improve the functional scale in patients with irritable bowel
syndrome. Probiotics can have therapeutic effects for IBS patients.
PMID- 26435826
TI - The Effect of Educational Intervention on Nurses' Attitudes Toward the Importance
of Family-Centered Care in Pediatric Wards in Iran.
AB - INTRODUCTION: Family-centered care sustains the unity of the child's and the
family's health. The aim of this study was to determine nurses' attitudes toward
parents' participation in the care of their hospitalized children in Iran in
2015. METHODS: In this experimental study, 200 pediatric nurses from hospitals
affiliated with the Shaheed Beheshti University of Medical Sciences in Tehran
were selected using the multi-stage, random-sampling method. Data were gathered
using a questionnaire that covered demographic information and nurses' attitudes.
The questionnaire consisted of 31 items and was completed by the nurses in three
stages: 1) before intervention (pre-test), 2) immediately after intervention
(post-test), and 3) three months after intervention (follow-up). The data were
analyzed via SPSS software and using descriptive and analytical methods.
Descriptive statistics, the Spearman Correlation Coefficient, and Repeated
Measure Analysis (the Bonferroni method) were used to assess the data. RESULTS:
The results indicated that there was a significant increase in the mean score of
attitude after intervention [M (pre) = 3.35%, M (post) = 3.97%, p < 0.001)]. Most
of subjects had neutral attitudes toward family participation in their children's
care. There were no significant relationship between the nurses' socio
demographic characteristics and their attitudes. CONCLUSION: The nurses'
attitudes toward the family's participation in the care of their hospitalized
children were moderate. The nurses' attitudes should be improved by taking part
in continuous training programs.
PMID- 26435827
TI - The Role of Hemostatic Factors in Atherosclerosis in Patients with Chronic Renal
Disease.
AB - INTRODUCTION: Atherosclerotic cardiovascular disease remains the leading cause of
increased morbidity and mortality observed in chronic kidney disease (CKD)
patients. Endothelial dysfunction (ED) is thought to be a key initial event in
the development of atherosclerosis. The aim of this study was to evaluate the
potential role of hemostatic factors in atherosclerosis, thrombosis and
cardiovascular complications in patients suffering from chronic renal disease.
METHODS: The study was conducted on 50 renal patients divided into two groups of
equal size. Group 1 consisted of 25 patients with end-stage renal disease (ESRD)
on regular hemodialysis. Group 2 consisted of 25 chronic renal disease patients
on conservative treatment. Twenty age- and sex-matched healthy subjects were
included in the study to serve as a control group. Thrombomodulin (TM), von
Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen
activator inhibitor (PAI-1) and hsCRP were assessed. High-resolution B-mode
ultrasonography of both the common and internal carotid arteries to measure
carotid intima media thickness (CIMT) was performed on all subjects. RESULTS:
There were highly significant increases in hsCRP, TM, vWF, tPA and PAI-1 in both
patient groups compared to the control group (P<0.01 for all except for TM
between group 2 and 3 P<0.05) with significant increase in group 1 compared to
group 2 (P<0.01). In addition, there was a highly significant increase in CIMT in
both patient groups compared to the control group (P<0.01) with a significant
increase in group 1 compared to group 2 (P<0.05). The study revealed significant
positive correlation of hemostatic factors (TM, vWf, PAI-1 & t-PA) with
creatinine, urea, hsCRP & CIMT. CONCLUSION: CKD patients have increased risk of
atherosclerosis as measured by CIMT, which is used as a surrogate marker of early
atherosclerosis and has been shown to be a strong predictor of future myocardial
infarction and stroke. They have high levels of TM, vWF, tPA, PAI-1 that
correlate with kidney function, hsCRP and CIMT. Therefore, these abnormalities in
hemostasis may account for the increased risk of atherothrombosis in these
patients. The elevated hsCRP levels and their correlation to hemostatic factors
and CIMT might provide an important clue to link a systemic marker of
inflammation to atherosclerosis. Further research is required to better
understand the procoagulant state in patients with CKD.
PMID- 26435828
TI - Iontophoresis Versus Cyriax-Type exercises in Chronic Tennis Elbow among
industrial workers.
AB - INTRODUCTION: Tennis elbow (TE) is one of the most commonly encountered upper
limb conditions. It mainly affects people who use the hand grip against
resistance frequently, resulting in microtrauma to the wrist extensors tendon,
causing pain. This study was conducted to compare the application of
iontophoresis of 0.4% dexamethasone and Cyriax-type exercises in the treatment of
chronic tennis elbow (CTE). METHODS: Twenty-two industrial worker diagnosed as
having CTE participated in this study, and their ages ranged from 25 to 52. They
were assigned randomly to two groups, i.e., "group A" in which the workers were
treated by iontophoresis of 0.4% Dexamethasone and "group B" in which the workers
were treated by conducting Cyriax-type exercises on the affected tendon. Both
groups received stretching exercises for the common extensors tendon for 10
minutes in addition to five minutes of pulsed US 1.1 W/cm2 six times over two
weeks. The outcome of the treatment was assessed one week after the last session
by the visual analog scale (VAS) to assess pain, by the Oxford elbow score (OES)
to measure the patient's satisfaction, and by a handgrip dynamometer to measure
the strength of the handgrip. RESULTS: The application of 0.4% dexamethasone
iontophoresis and the use of Cyriax-type exercises both provided significant
improvement in the pain, patient's satisfaction, and the power of the handgrip,
and there were no significant difference (p > 0.001) in any of the three measures
after the first week's treatment. CONCLUSIONS: Both iontophoresis of 0.4%
dexamethasone and Cyriax-type exercises were successful as treatment modalities
for patients with CTE, and there were no significant differences between both of
them in the treatment of those cases.
PMID- 26435829
TI - Study of the self-confidence of midwifery graduates from Mashhad College of
nursing and midwifery in fulfilling clinical skills.
AB - INTRODUCTION: Self-confidence is one of the main components of clinical
competence, and it is considered to be an important indicator of ability and
competence. The aim of this study was to determine the confidence of midwifery
graduates from Mashhad College of nursing and midwifery in fulfilling the
required clinical skills. METHODS: The study was in the form of a cross-sectional
study, and it was performed in 2011 on 50 midwifery graduates who had been
working in health centers in Mashhad for six months to three years providing
midwifery services, as well as on their supervisors having a minimum of 6 months
experiences of responsibility in these centers. The research tools included self
assessment tools of self-confidence in midwives and assessment tools of self
confidence in midwifery graduates in fulfilling clinical skills performed by the
supervisors. The validity of the tools was confirmed by face validity and content
validity, and the reliability of the test was confirmed by test-retest (r =
0.82). After the data were extracted and encoded, they were analyzed using SPSS
software version 11.5, descriptive statistics, the t-test, and Pearson's test.
RESULTS: Among the midwifery graduates, 84.57% of them had confidence in the area
of management of low-risk situations, and 55.51% had confidence in their ability
to manage high-risk situations. The self-confidence levels of graduates in
fulfilling clinical skills in the management of low-risk and high-risk situations
were significantly different (P < 0.05). Clinical skills had a positive
correlation with self-confidence (P < 0.05, r = 0.85). CONCLUSION: Improvements
were needed in the self-confidence of graduates in fulfilling clinical skills in
the management of high-risk situations. In order to achieve such improvement, it
is necessary to identify and use methods of increasing graduates' self-confidence
in the learning environment by developing an enhanced midwifery curriculum and
improved teaching methods.
PMID- 26435830
TI - Diacerein: A potential therapeutic drug for the management of experimental
periodontitis in rats.
AB - INTRODUCTION: Knowledge about the pathogenic process in the progression of
periodontal disease indicates that the central cause of periodontal disease is
the loss of a healthy balance between microbial virulence factors and the host's
inflammatory response. The aim of this study was to evaluate the potential
effectiveness of diacerein as an anti-inflammatory drug in the management of
experimental periodontitis in rats. METHODS: The study included 60 albino rats
that were divided into two groups. Periodontitis was induced in both groups. The
drug group received systemic administration of diacerein, and the control group
received a placebo. IL-1beta was measured two weeks after the induction of
periodontitis and before the administration of the drug (baseline measurement),
and it was measured again at the end of two and end of four weeks after scaling
and root planning and diacerein administration. RESULTS: The results indicated
that there was a significant decrease in IL-1beta level in both groups. For the
control group, there were significant decreases of the IL-1beta values from the
baseline to two weeks and also from the baseline to four weeks, with p-values of
0.0001 for both comparisons. The same results were obtained for the drug group.
CONCLUSION: It was concluded that it is likely that diacerein may play a
therapeutic role as a potent anti-inflammatory drug in the management of
periodontitis.
PMID- 26435831
TI - Evaluation of the orientation of the steepest meridian of regular astigmatism
among highly myopic Egyptian patients seeking non-ablative surgical correction of
the refractive error.
AB - INTRODUCTION: LASIK surgery is currently the preferred procedure to correct low
to moderate myopia. The aim of this study was to determine the orientation of the
steepest meridian of regular astigmatism in order to determine the relative
incidence of vertical, horizontal, and oblique regular astigmatism among highly
myopic Egyptian patients seeking non-ablative surgical correction of the
refractive error. METHODS: One hundred and one eyes of 68 highly myopic patients
who were seeking refractive surgery were included in this consecutive case series
study. The refractive errors were measured using an autorefractometer and
confirmed by trial. We measured the uncorrected and best corrected visual acuity
in Snellen lines. Keratometry, central corneal thickness, and anterior chamber
depth also were measured. The cylinder power in diopters and the axis in degrees
were reported. Astigmatism was graded as with the rule (i.e., vertical meridian
steeper), against the rule (i.e., horizontal meridian steeper), and oblique
astigmatism. The number and the percentage of eyes with the rule, against the
rule, and oblique astigmatism were calculated, and the chi-squared test was
performed to analyze the data. RESULTS: The spherical refractive error ranged
from -6.5 to -24.5 diopters (-13.45 +/- 4.60). The cylinder power (Cyl) ranged
from -0.25 to -7.5 diopters (-2.23 +/- 1.28). The uncorrected visual acuity
(UCVA) in Snellen lines ranged from 0.01 - 0.1 (0.03 +/- 0.02). The mean for best
corrected visual acuity (BCVA) in Snellen lines was 0.40 (+/- 0.23). The steepest
meridian was vertical (i.e., with-the-rule astigmatism) in 44 eyes (43.56%),
horizontal (i.e., against-the-rule astigmatism) in 27 eyes (26.73%), and oblique
(i.e., oblique astigmatism) in 30 eyes (29.70%). CONCLUSIONS: The incidence of
with-the-rule astigmatism in patients with high myopia was found to be much lower
than in previous studies for non-myopic patients, with a higher incidence for
against-the-rule astigmatism and oblique astigmatism.
PMID- 26435832
TI - Insistence on sameness relates to increased covariance of gray matter structure
in autism spectrum disorder.
AB - BACKGROUND: Autism spectrum disorder (ASD) is characterized by atypical
development of cortical and subcortical gray matter volume. Subcortical
structural changes have been associated with restricted and repetitive behavior
(RRB), a core component of ASD. Behavioral studies have identified insistence on
sameness (IS) as a separable RRB dimension prominent in high-functioning ASD,
though no simple brain-behavior relationship has emerged. Structural covariance,
a measure of morphological coupling among brain regions using magnetic resonance
imaging (MRI), has proven an informative measure of anatomical relationships in
typical development and neurodevelopmental disorders. In this study, we use this
measure to characterize the relationship between brain structure and IS. METHODS:
We quantified the structural covariance of cortical and subcortical gray matter
volume in 55 individuals with high-functioning ASD using 3T MRI. We then related
these structural metrics to individual IS scores, as assessed by the Repetitive
Behavior Scale-Revised (RBS-R). RESULTS: We found that increased coupling among
subcortical regions and between subcortical and cortical regions related to
greater IS symptom severity. Most pronounced, the striatum and amygdala
participated in a plurality of identified relationships, indicating a central
role for these structures in IS symptomatology. These structural associations
were specific to IS and did not relate to any of the other RRB subcomponents
measured by the RBS-R. CONCLUSIONS: This study indicates that behavioral
dimensions in ASD can relate to the coordination of development across multiple
brain regions, which might be otherwise obscured using typical brain-behavior
correlations. It also expands the structures traditionally related to RRB in ASD
and provides neuroanatomical evidence supportive of IS as a separate RRB
dimension. TRIAL REGISTRATION: ClinicalTrials.gov NCT01031407.
PMID- 26435834
TI - Stem cell aging in adult progeria.
AB - Aging is considered an irreversible biological process and also a major risk
factor for a spectrum of geriatric diseases. Advanced age-related decline in
physiological functions, such as neurodegeneration, development of cardiovascular
disease, endocrine and metabolic dysfunction, and neoplastic transformation, has
become the focus in aging research. Natural aging is not regarded as a programmed
process. However, accelerated aging due to inherited genetic defects in patients
of progeria is programmed and resembles many aspects of natural aging. Among
several premature aging syndromes, Werner syndrome (WS) and Hutchinson-Gilford
progeria syndrome (HGPS) are two broadly investigated diseases. In this review,
we discuss how stem cell aging in WS helps us understand the biology of aging. We
also discuss briefly how the altered epigenetic landscape in aged cells can be
reversed to a "juvenile" state. Lastly, we explore the potential application of
the latest genomic editing technique for stem cell-based therapy and regenerative
medicine in the context of aging.
PMID- 26435836
TI - Are personality disturbances in anorexia nervosa related to emotion processing or
eating disorder symptomatology?
AB - BACKGROUND: Anorexia Nervosa (AN) is a psychiatric illness associated with a
number of personality disturbances. However, whether these personality
characteristics are related to eating disorder symptomatology or emotion
regulation is unclear. The aim of this study was to investigate these
relationships. RESULTS: Twenty-four individuals with AN and 25 age- and premorbid
intelligence-matched controls completed the Personality Diagnostic Questionnaire,
and scores were correlated with measures of emotionality and negative mood
states, and eating disorder symptomatology. AN was associated with increased
scores on schizoid, borderline, avoidant, dependent, obsessive compulsive,
negativistic and depressive personality dimensions, relative to controls. In AN,
eating disorder symptomatology did not significantly correlate with scores on any
personality dimension. However, a number of personality characteristics were
found to correlate with negative mood states. CONCLUSIONS: The findings suggest
that personality disturbances in AN are not related to disorder-specific
symptoms, but are related to negative mood states.
PMID- 26435837
TI - The effect of indoor office environment on the work performance, health and well
being of office workers.
AB - BACKGROUND: The effect of indoor environment may have an influence on the
performance, productivity health and well-being of office workers. METHODS:
Environmental factors such as indoor temperature and illumination have been
investigated at three levels. A neurobehavioral test (NBT) has been proposed for
the evaluation of office workersc performance. A field lab to emulate an office
has been created. In controlled condition of environmental factors, the
neurobehavioral test was conducted. The response time and the number of errors in
each test have been recorded. A randomized block factorial design was used to
analyze the responses of office worker's performance. RESULTS: The results
revealed that the independent and interaction effect of temperature and
illumination have significant effect on the office workers' performance. The
effect of indoor room temperature has more influences than the effect of
illumination. The effect of indoor temperature has 38.56% of contribution on the
performance. The optimum levels of indoor temperature at 21 degrees C and
illumination at 1000 lux have improved the work performance and health of office
workers. CONCLUSION: The indoor room temperature and illumination are more
influence on the performance of the office workers. It may be concluded that the
impact of indoor room temperature (38.56%) is more on the office worker's
performance than the effect of illumination (19.91%). Further, it may be
concluded that the optimum level of indoor room temperature (21 degrees C) and
illumination (1000lux) have improved the work performance, health and
productivity of office workers.
PMID- 26435835
TI - Enzymatic and non-enzymatic isolation systems for adipose tissue-derived cells:
current state of the art.
AB - In the past decade, adipose tissue became a highly interesting source of adult
stem cells for plastic surgery and regenerative medicine. The isolated stromal
vascular fraction (SVF) is a heterogeneous cell population including the adipose
derived stromal/stem cells (ASC), which showed regenerative potential in several
clinical studies and trials. SVF should be provided in a safe and reproducible
manner in accordance with current good manufacturing practices (cGMP). To ensure
highest possible safety for patients, a precisely defined procedure with a high
quality control is required. Hence, an increasing number of adipose tissue
derived cell isolation systems have been developed. These systems aim for a
closed, sterile, and safe isolation process limiting donor variations, risk for
contaminations, and unpredictability of the cell material. To isolate SVF from
adipose tissue, enzymes such as collagenase are used. Alternatively, in order to
avoid enzymes, isolation systems using physical forces are available. Here, we
provide an overview of known existing enzymatic and non-enzymatic adipose tissue
derived cell isolation systems, which are patented, published, or already on the
market.
PMID- 26435838
TI - Improving preparedness of medical students and junior doctors to manage patients
with diabetes.
AB - OBJECTIVE: New medical graduates are the front-line staff in many hospital
settings and manage patients with diabetes frequently. Prescribing is an area of
concern for junior doctors, however, with insulin prescribing reported as a
particular weakness. This study aimed to produce an educational intervention
which aimed to improve preparedness to manage patients with diabetes and evaluate
it using a mixed methods approach. RESEARCH DESIGN AND METHODS: An e-resource
(http://www.diabetesscenariosforjuniordoctors.co.uk) was created to contain
commonplace and authentic diabetes decision-making scenarios. -32 junior doctors
(n=20) and year 5 students (n=12) in South West England worked through the
scenarios while 'thinking aloud' and then undertook a semistructured interview.
Qualitative data were transcribed verbatim and analyzed thematically. Participant
confidence to manage patients with diabetes before, immediately after, and 6
weeks after the educational intervention was also measured using a self-rating
scale. RESULTS: Participants reported that patients with diabetes were daunting
to manage because of the wide array of insulin products, their lack of confidence
with chronic disease management and the difficulty of applying theory to
practice. The e-resource was described as authentic, practical, and appropriate
for the target audience. Junior doctors' self-rated confidence to manage patients
with diabetes increased from 4.7 (of 10) before using the e-resource, to 6.4
immediately afterwards, and 6.8 6 weeks later. Medical students' confidence
increased from 5.1 before, to 6.4 immediately afterwards, and 6.4 6 weeks later.
CONCLUSIONS: Providing opportunities to work with authentic scenarios in a safe
environment can help to ameliorate junior doctors' lack of confidence to manage
patients with diabetes.
PMID- 26435839
TI - Lipid-lowering treatment patterns among patients with type 2 diabetes mellitus
with high cardiovascular disease risk.
AB - OBJECTIVE: To examine real-world treatment patterns of lipid-lowering treatment
and their possible associated intolerance and/or ineffectiveness among patients
with type 2 diabetes mellitus initiating statins and/or ezetimibe. RESEARCH
DESIGN AND METHODS: Adult (aged >=18 years) patients diagnosed with type 2
diabetes who initiated statins and/or ezetimibe from January 1, 2007 to June 30,
2011 were retrospectively identified from the IMS LifeLink Pharmetrics Plus
commercial claims database. Patients were further classified into 3 high-risk
cohorts: (1) history of cardiovascular event (CVE); (2) two risk factors (age and
hypertension); (3) aged >=40 years. Patients had continuous health plan enrolment
>=1 year preindex and postindex date (statin and/or ezetimibe initiation date).
Primary outcomes were index statin intensity, treatment modification(s), possible
associated statin/non-statin intolerance and/or ineffectiveness issues (based on
treatment modification type), and time-to-treatment modification(s). Analyses for
each cohort were stratified by age groups (<65 and >=65 years). RESULTS: A total
of 9823 (history of CVE), 62 049 (2 risk factors), and 128 691 (aged >=40 years)
patients were included. Among patients aged <65 years, 81.4% and 51.8% of those
with history of CVE, 75.6% and 44.4% of those with 2 risk factors, and 77.9% and
47.1% of those aged >=40 years had >=1 and 2 treatment modification(s),
respectively. Among all patients, 23.2-28.4% had possible statin intolerance
and/or ineffectiveness issues after accounting for second treatment modification
(if any). CONCLUSIONS: Among patients with type 2 diabetes with high
cardiovascular disease risk, index statin treatment modifications that
potentially imply possible statin intolerance and/or ineffectiveness were
frequent.
PMID- 26435840
TI - The talent study: a multicentre randomized controlled trial assessing the impact
of a 'tailored lifestyle self-management intervention' (talent) on weight
reduction.
AB - BACKGROUND: Overweight is considered an important risk factor for diseases in the
context of metabolic syndrome. Lifestyle modifications are the means of choice to
reduce weight in persons with a Body Mass Index of 28 to 35. The study examines
whether there are any differences between two intervention strategies regarding
weight reduction in overweight persons. METHODS/DESIGN: The study is a
multicentre randomized controlled trial with observation duration of 12 months.
Eight study centres are involved to include a minimal sample size of 150
participants. Randomization ratio is 2:1. Feasible persons are checked according
to inclusion and exclusion criteria and after given informed consent are assigned
randomly to one of two intervention programs: A) intervention group:
comprehensive lifestyle modification program (Individual Health Management IHM)
with 3 months reduction phase plus 9 months maintaining phase, B) control group:
written information with advice for healthy food habits (Usual care UC).
Participants of the IHM group have access to a web-based health portal and join 3
full-day and 10 two-hour training sessions during the first 3 months. During the
remaining 9 months four refresh trainings will be performed. There are 3
different diet strategies (fasting, two-day diet, meal replacement) for free
choice. Participants of the control group are provided with acknowledged rules
for healthy food according to the German Nutrition Society (DGE). Examinations
are conducted at baseline, after 3, 6, 9 and 12 months. They include body weight,
waist circumference, blood pressure, laboratory findings and a bio-impedance
analysis to measure body composition. Statistical analysis of the primary outcome
'change of body weight after 12 months' is based on ITT population including
analysis of variance of the weight differences between month 0 and 12 with the
factors 'group', 'baseline value' and 'study centre'. Secondary outcomes will be
analyzed exploratively. DISCUSSION: The monitoring of the study will implement
different measures to enhance compliance, avoid attrition and ensure data
quality. Based on a blended learning concept and using web-based e-health tools
the program promises to achieve sustainable effects in weight reduction. TRIAL
REGISTRATION: German Clinical Trials Register Freiburg (DRKS): DRKS00006736 (date
registered 20/09/2014).
PMID- 26435841
TI - Coronary artery disease is associated with persistent lower quality of life in
women.
PMID- 26435842
TI - Sticks AND Carrots: Encouraging Open Science at its source.
AB - The Open Science (OS) movement has been seen as an important facilitator for
public participation in science. This has been underpinned by the assumption that
widespread and free access to research outputs leads to (i) better and more
efficient science, (ii) economic growth, in particular for small and medium-sized
enterprises wishing to capitalise on research findings and (iii) increased
transparency of knowledge production and its outcomes. The latter in particular
could function as a catalyst for public participation and engagement. Whether OS
is likely to help realise these benefits, however, will depend on the emergence
of systemic incentives for scientists to utilise OS in a meaningful manner. While
some areas, the environmental sciences have a long tradition of open ethos,
citizen inclusion and global collaborations, such activities need to be more
systematically supported and promoted by funders and learned societies in order
to improve scientific research and public participation.
PMID- 26435844
TI - Performance and carcass characteristics of Australian purebred and crossbred
lambs supplemented with Rice Bran.
AB - BACKGROUND: This study examined the effects of dietary supplementation with rice
bran, sire breed and gender on live animal performance and carcass
characteristics in Australian crossbred and purebred Merino lambs. METHODS: Forty
eight lambs balanced by sire breed (Dorset, White Suffolk, Merino) and gender
(ewe, wether) were randomly allocated into three dietary supplementation groups
(Control- 24 lambs fed wheat/barley-based pellets, Low- 12 animals fed a 50/50
ratio of wheat-based/rice bran pellets, and High- 12 lambs fed rice bran
pellets). The Rice bran pellets replaced 19 % of the barley component of the
feed. Animals were group-fed at the rate of 1000 g of the supplement per head per
day with ad libitum access to lucerne hay as the basal diet and water. The
duration of the feeding trial was 49 days with an initial 21-day adjustment
period. RESULTS: Sire breed differences were evident for initial (p < 0.0002) and
final (p < 0.0016) liveweights, hot carcass (p < 0.0030) and cold carcass (p <
0.0031) weights, as well as dressing percentage (p < 0.0078), fat thickness (p <
0.0467), yield grade (p < 0.0470) and rib eye area (p < 0.0022) with purebred
Merino under-performing compared to the crossbreds. Concentrate feed conversion
efficiency, costs per unit of liveweight gain and over the hooks income were
comparable between treatments regardless of the observed trend where the high
supplementation group tended to show lower feed intake (745.8 g/day) compared to
both the control (939.9 g/day) and low supplementation groups (909.6 g/day). No
significant differences (p > 0.05) were observed between treatments for live
animal performance, carcass characteristics, gender and their second-order
interactions. CONCLUSIONS: Results indicate that Rice bran can be utilised as a
cost-effective supplementary feed source in genetically divergent sheep over a 49
day feeding period without detrimental effects on overall live animal performance
or carcass characteristics.
PMID- 26435843
TI - Improving mental health among people living with HIV: a review of intervention
trials in low- and middle-income countries.
AB - People living with HIV (PLWH) experience greater psychological distress than the
general population. Evidence from high-incomes countries suggests that
psychological interventions for PLWH can improve mental health symptoms, quality
of life, and HIV care engagement. However, little is known about the
effectiveness of mental health interventions for PLWH in low and middle-income
countries (LMICs), where the large majority of PLWH reside. This systematized
review aims to synthesize findings from mental health intervention trials with
PLWH in LMICs to inform the delivery of mental health services in these settings.
A systematic search strategy was undertaken to identify peer-reviewed published
papers of intervention trials addressing negative psychological states or
disorders (e.g., depression, anxiety) among PLWH in LMIC settings. Search results
were assessed against pre-established inclusion and exclusion criteria. Data from
papers meeting criteria were extracted for synthesis. Twenty-six papers,
published between 2000 and 2014, describing 22 unique interventions were
identified. Trials were implemented in sub-Saharan Africa (n=13), Asia (n=7), and
the Middle East (n=2), and addressed mental health using a variety of approaches,
including cognitive-behavioral (n=18), family-level (n=2), and pharmacological
(n=2) treatments. Four randomized controlled trials reported significant
intervention effects in mental health outcomes, and eleven preliminary studies
demonstrated promising findings. Among the limited mental health intervention
trials with PLWH in LMICs, few demonstrated efficacy. Mental health interventions
for PLWH in LMICs must be further developed and adapted for resource-limited
settings to improve effectiveness.
PMID- 26435845
TI - Unpacking externalising problems: negative parenting associations for conduct
problems and irritability.
AB - BACKGROUND: Reciprocal associations between negative parenting and child
externalising problems are well documented, but measures commonly include child
irritability, masking potential distinct associations for irritability and
conduct problems. AIMS: To illuminate links between negative parenting, child
conduct problems and irritability over time. METHOD: A cross-lagged monozygotic
(MZ) twin differences design was used in a UK sample (3154 twin pairs) at 4, 7
and 9 years. RESULTS: Within-pair MZ differences in negative parenting were found
to relate longitudinally to differences in conduct problems and irritability. Of
note, negative parenting at age 7 was found to relate particularly to increased
irritability at 9 years. CONCLUSIONS: Once genetics are taken into account,
irritability in middle childhood may be particularly vulnerable to negative
parenting, suggesting support for its malleability to parent-based intervention.
PMID- 26435847
TI - Molecular Imaging of Tumors Using a Quantitative T 1 Mapping Technique via
Magnetic Resonance Imaging.
AB - Magnetic resonance imaging (MRI) of glioblastoma multiforme (GBM) with molecular
imaging agents would allow for the specific localization of brain tumors. Prior
studies using T 1-weighted MR imaging demonstrated that the SBK2-Tris-(Gd-DOTA)3
molecular imaging agent labeled heterotopic xenograft models of brain tumors more
intensely than non-specific contrast agents using conventional T 1-weighted
imaging techniques. In this study, we used a dynamic quantitative T 1 mapping
strategy to more objectively compare intra-tumoral retention of the SBK2-Tris-(Gd
DOTA)3 agent over time in comparison to non-targeted control agents. Our results
demonstrate that the targeted SBK2-Tris-(Gd-DOTA)3 agent, a scrambled-Tris-(Gd
DOTA)3 control agent, and the non-specific clinical contrast agent Optimark(TM)
all enhanced flank tumors of human glioma cells with similar maximal changes on T
1 mapping. However, the retention of the agents differs. The non-specific agents
show significant recovery within 20 min by an increase in T 1 while the specific
agent SBK2-Tris-(Gd-DOTA)3 is retained in the tumors and shows little recovery
over 60 min. The retention effect is demonstrated by percent change in T 1 values
and slope calculations as well as by calculations of gadolinium concentration in
tumor compared to muscle. Quantitative T 1 mapping demonstrates the superior
binding and retention in tumors of the SBK2-Tris-(Gd-DOTA)3 agent over time
compared to the non-specific contrast agent currently in clinical use.
PMID- 26435846
TI - Potential Risks in the Paradigm of Basic to Translational Research: A Critical
Evaluation of qPCR Telomere Size Techniques.
AB - Real time qPCR has become the method of choice for rapid large-scale telomere
length measurements. Large samples sizes are critical for clinical trials, and
epidemiological studies. QPCR has become such routine procedure that it is often
used with little critical analysis. With proper controls, the mean telomere size
can be derived from the data and even the size can be estimated. But there is a
need for more consistent and reliable controls that will provide closer to the
actual mean size can be obtained with uniform consensus controls. Although
originating at the level of basic telomere research, many researchers less
familiar with telomeres often misunderstand the source and significance of the
qPCR metric. These include researchers and clinicians who are interested in
having a rapid tool to produce exciting results in disease prognostics and
diagnostics than in the multiple characteristics of telomeres that form the basis
of the measurement. But other characteristics of the non-bimodal and
heterogeneous telomeres as well as the complexities of telomere dynamics are not
easily related to qPCR mean telomere values. The qPCR metric does not reveal the
heterogeneity and dynamics of telomeres. This is a critical issue since mutations
in multiple genes including telomerase can cause telomere dysfunction and a loss
of repeats. The smallest cellular telomere has been shown to arrest growth of the
cell carrying the dysfunction telomere. A goal for the future is a simple method
that takes into account the heterogeneity by measuring the highest and lowest
values as part of the scheme to compare. In the absence of this technique,
Southern blots need to be performed in a subset of qPCR samples for both mean
telomere size and the upper and lower extremes of the distribution. Most
importantly, there is a need for greater transparency in discussing the
limitations of the qPCR data. Given the potentially exciting qPCR telomere size
results emerging from clinical studies that relate qPCR mean telomere size
estimates to disease states, the current ambiguities have become urgent issues to
validate the findings and to set the right course for future clinical
investigations.
PMID- 26435848
TI - Screening of Small Molecule Microarrays for Ligands Targeted to the Extracellular
Epitopes of Living Cells.
AB - The screening of living cells using high-throughput microarrays is technically
challenging. Great care must be taken in the chemical presentation of potential
ligands and the number of collisions that cells make with them. To overcome these
issues, we have developed a glass slide-based microarray system to discover small
molecule ligands that preferentially bind to one cell type over another,
including when the cells differ by only a single receptor. Chemical spots of 300
+/- 10 MUm in diameter are conjugated covalently to glass slides using an
arraying robot, and novel near-infrared fluorophores with peak emission at 700 nm
and 800 nm are used to label two different cell types. By carefully optimizing
incubation conditions, including cell density, motion, kinetics, detection, etc.
we demonstrate that cell-ligand binding occurs, and that the number of cells
bound per chemical spot correlates with ligand affinity and specificity. This
screening system lays the foundation for high-throughput discovery of novel
ligands to the cell surface.
PMID- 26435849
TI - Weight Maintenance with Litramine (IQP-G-002AS): A 24-Week Double-Blind,
Randomized, Placebo-Controlled Study.
AB - BACKGROUND: Litramine (IQP-G-002AS) was shown to be effective and safe for weight
loss in overweight and obese subjects. However, long-term effectiveness on
maintenance of body weight loss has yet to be ascertained. OBJECTIVE: To assess
effect of Litramine on maintenance of body weight loss. METHODS: A double-blind,
randomised, placebo-controlled trial on overweight and obese patients was
conducted over two sites in Germany for 24 weeks. Subjects with documented
previous weight loss of 3% over the last 3-6 months were randomised to groups
given either Litramine (3 g/day) or a matching placebo. Primary endpoints were
difference of mean body weight (kg) between baseline and end of study and
maintenance of initially lost body weight in verum group, where maintenance is
defined as <=1% weight gain. RESULTS: Subjects who were taking Litramine lost
significantly more body weight compared to the subjects taking placebo who gained
weight instead (-0.62 +/- 1.55 kg versus 1.62 +/- 1.48 kg, p < 0.001). More
importantly, 92% of subjects in Litramine group were able to maintain their body
weight after initial weight loss, versus 25% in placebo group. No serious adverse
events were reported throughout. CONCLUSION: Litramine is effective and safe for
long-term body weight maintenance. Trial Registration. This trial is registered
with Clinicaltrials.gov identifier: NCT01505387.
PMID- 26435850
TI - Visual Interhemispheric and Striate-Extrastriate Cortical Connections in the
Rabbit: A Multiple Tracer Study.
AB - Previous studies in rabbits identified an array of extrastriate cortical areas
anatomically connected with V1 but did not describe their internal topography. To
address this issue, we injected multiple anatomical tracers into different
regions in V1 of the same animal and analyzed the topography of resulting
extrastriate labeled fields with reference to the patterns of callosal
connections and myeloarchitecture revealed in tangential sections of the
flattened cortex. Our results extend previous studies and provide further
evidence that rabbit extrastriate areas resemble the visual areas in rats and
mice not only in their general location with respect to V1 but also in their
internal topography. Moreover, extrastriate areas in the rabbit maintain a
constant relationship with myeloarchitectonic borders and features of the
callosal pattern. These findings highlight the rabbit as an alternative model to
rats and mice for advancing our understanding of cortical visual processing in
mammals, especially for projects benefiting from a larger brain.
PMID- 26435851
TI - Novel Longitudinal and Propensity Score Matched Analysis of Hands-On Cooking and
Nutrition Education versus Traditional Clinical Education among 627 Medical
Students.
AB - Background. Physicians are inadequately equipped to respond to the global obesity
and nutrition-associated chronic disease epidemics. We investigated superiority
of simulation-based medical education with deliberate practice (SBME-DP) hands-on
cooking and nutrition elective in a medical school-based teaching kitchen versus
traditional clinical education for medical students. Materials and Methods. A 59
question panel survey was distributed to an entire medical school twice annually
from September 2012 to May 2014. Student diet and attitudes and competencies
(DACs) counseling patients on nutrition were compared using conditional
multivariate logistic regression, propensity score-weighted, and longitudinal
panel analyses. Inverse-variance weighted meta-analysis (IVWM) was used for
planned subgroup analysis by year and treatment estimates across the three
methods. Results. Of the available 954 students, 65.72% (n = 627) unique students
were followed to produce 963 responses. 11.32% (n = 109) of responses were from
84 subjects who participated in the elective. SBME-DP versus traditional
education significantly improved fruit and vegetable diet (OR = 1.38, 95% CI:
1.07-1.79, p = 0.013) and attitudes (OR = 1.81, 95% CI: 1.40-2.35, p < 0.001) and
competencies (OR = 1.72, 95% CI: 1.54-1.92, p < 0.001). Conclusions. This study
reports for the first time superiority longitudinally for SBME-DP style nutrition
education for medical students which has since expanded to 13 schools.
PMID- 26435852
TI - A Report of Accelerated Coronary Artery Disease Associated with Cerebral
Autosomal Dominant Arteriopathy with Subcortical Infarcts and
Leukoencephalopathy.
AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL) is the most common heritable form of vascular
dementia and it is caused by mutations in the NOTCH3 gene. The neurologic
manifestations of CADASIL syndrome have been well characterized; however, here we
report one of the first de novo cases of CADASIL-associated coronary artery
disease. A 45-year-old woman with a history of CADASIL and remote tobacco use
presented with unstable angina. She was found to have diffuse and irregular
narrowing of the left anterior descending artery and a drug eluting stent was
deployed. Months later, she developed two subsequent episodes of unstable angina,
requiring stent placement in the distal left anterior descending artery and the
right coronary artery. Though the neurologic manifestations of CADASIL have been
well described, these patients may also be predisposed to developing premature
coronary artery disease. Patients with CADASIL and their physicians should be
aware of this possible association because these patients may not be identified
as high risk by traditional cardiovascular risk estimators. These patients may
benefit from more aggressive interventions to reduce cardiac risk.
PMID- 26435853
TI - Culture Negative Stent Infection in an Infant with Hypoplastic Left Heart and
Persistent Fever.
AB - We present an infant with hypoplastic left heart with persistent fever despite
two courses of antibiotics and repeatedly negative blood cultures. He eventually
underwent surgical extraction of two stents. The stent cultures became positive;
he was treated with 4 weeks of antibiotics and the fever resolved.
PMID- 26435854
TI - A Rare Case of Aortic Valve Thrombosis in Patient with Idiopathic
Hypereosinophilic Syndrome.
AB - Idiopathic hypereosinophilic syndrome (HES) is characterized by persistent
eosinophilia and eosinophil-mediated organ-system damage. Cardiac thrombosis and
thromboembolic complications represent common causes of morbidity and mortality
and usually involve cardiac ventricles or mitral and prosthetic valves, while the
involvement of the aortic valve is extremely rare in HES. Here we report peculiar
multimodality images of an atypical case of extended thrombosis of the aortic
valve, complicated by myocardial ischemia and asymptomatic cerebral ischemia,
likely due to thrombus embolization, occurring in a 48-year-old man with HES.
Prompt anticoagulant and steroid therapy lead to rapid and complete resolution of
the thrombotic lesions, allowing preserving the native valve and preventing
further embolic events.
PMID- 26435855
TI - Mediastinal Packing for Intractable Coagulopathy in Acute Aortic Dissection
(Types 1 and 2 DeBakey): A Life-Saving Technique-Report of Experiences.
AB - Nonsurgical bleeding after complex thoracic aortic procedures (such as aortic
dissection and aortic aneurysm) is a great challenge for cardiac surgeons because
of severe coagulopathy, exsanguinous bleeding, and inevitable death. Temporary
mediastinal packing (with sponge) in such cases is the only life-saving technique
with good result in most cases. Herein, we presented three cases with acute
aortic dissection with intractable bleeding that was successfully managed with
mediastinal packing.
PMID- 26435857
TI - Dental Considerations in Children with Glucose-6-phosphate Dehydrogenase
Deficiency (Favism): A Review of the Literature and Case Report.
AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an uncommon inherited
enzyme deficiency characterized by hemolytic anemia, caused by the inability of
erythrocytes to detoxify oxidizing agents such as drugs, infectious diseases, or
fava bean ingestion. In this later case, the disorder is known as favism. The aim
of the present report was to present a review of the literature in this disease,
to describe a case report concerning an affected 9-year-old male, and to review
the main implications and precautions in pediatric dental management.
PMID- 26435856
TI - Primary Chronic Osteomyelitis of the Jaws in Children: An Update on
Pathophysiology, Radiological Findings, Treatment Strategies, and Prospective
Analysis of Two Cases.
AB - Objective. Primary chronic osteomyelitis (PCO) of the jaws in children is
associated with pain, trismus, and swelling. In children, temporomandibular joint
involvement is rare and few studies have been published due to the relatively low
incidence. This paper presents two cases of mandibular PCO in children with the
involvement of the collum mandibulae. In addition, a review of the literature
regarding demographic data, histological, radiological, and laboratory findings,
and treatment strategies of PCO was also performed. Material and Methods.
Prospective analyses of two PCO cases. A PubMed search was used and the articles
were sorted according to their corresponding key area of focus. Results. Review
of the literature revealed twenty-four cases of PCO with two cases of mandibular
condyle involvement. The mean age was 18 years; the male to female ratio was 1 :
3. Most of the patients were treated with anti-inflammatory drugs in combination
with decortication. Clinical recurrence was seen in 7 cases. Conclusion. A
combination of anti-inflammatory drugs and surgical intervention appears to be
the first choice of treatment. However, surgical removal of necrotic tissue
adjacent to collum mandibulae has its limitations in children. Further
investigations are of utmost importance in order to increase our knowledge and
understanding of this disease.
PMID- 26435858
TI - Omalizumab for Urticarial Vasculitis: Case Report and Review of the Literature.
AB - Urticarial vasculitis is characterised by inflamed itching or burning red patches
or wheals that resemble urticaria but persist for greater than 24 hours. It is
often idiopathic but is sometimes associated with collagen-vascular disease,
particularly systemic lupus erythematosus. Treatment options include oral
antihistamines, oral corticosteroids, dapsone, colchicine or hydroxychloroquine.
We describe a male patient with urticarial vasculitis who was treated with
omalizumab (anti-IgE) with convincing results and provide a review of previous
reports of patients with urticarial vasculitis treated with omalizumab.
PMID- 26435859
TI - A Missed Case of Occult Bilateral Temporomandibular Dislocation Mistaken for
Dystonia.
AB - A 24-year-old male with a history of psychiatric disorder and no prior
significant temporomandibular joint (TMJ) pathology presented to the emergency
department for "lockjaw." Plain film X-rays of the mandible were read as
unremarkable by an attending radiologist, leading to the initial diagnosis of
medication-induced dystonic reaction. Following unsuccessful medical treatment a
maxillofacial computed tomography (CT) was ordered. CT confirmed bilateral
dislocation, illustrating the importance of clinical judgment, and limitations of
certain radiographic images. The authors believe this case to be the first
reported case in the medical literature of bilateral anterior TMJ dislocation
with a false negative X-ray.
PMID- 26435861
TI - Comment on "A Case of Healthcare Associated Pneumonia Caused by Chryseobacterium
indologenes in an Immunocompetent Patient".
PMID- 26435860
TI - Third Case of Streptococcus suis Infection in Greece.
AB - Streptococcus suis is a facultative anaerobic, Gram-positive coccus that can
cause severe disease to both pigs and humans. Its zoonotic potential was first
recognized in 1968 when the first human case of meningitis was reported in
Denmark. Since then, over 1600 human cases have been reported worldwide, the vast
majority of which originated in Southeast Asia, and, thus, S. suis has been
fairly characterized as an emerging pathogen. Infection in humans presents most
commonly as bacteremia and/or meningitis while less common clinical
manifestations such as endocarditis and septic arthritis can occur. S. suis
infection is extremely uncommon in Greece and this is the third human case to be
reported. Correct identification is of importance for optimization of
antimicrobial treatment and epidemiological monitoring.
PMID- 26435862
TI - Miliary Tuberculosis Induced Acute Liver Failure.
AB - Hepatobiliary tuberculosis is uncommon even in endemic countries. It is
associated with a high mortality and is even diagnosed early in the disease
course. Acute liver failure (ALF) caused by tuberculosis bacilli has been
reported in only a few reports. All previous cases have been diagnosed by
postmortem examination. Time to antituberculosis treatment is very critical. In
case of suggestive findings on clinical and radiologic examination,
antituberculosis treatment should be initiated immediately. Drug use can be a
challenge in patients with ALF. However, as long as the other possible causes of
ALF can be excluded and hepatotoxic drugs were avoided during the early course of
treatment, such a highly fatal presentation of tuberculosis can be treated
safely. Here, we report a case of acute liver failure as a presentation of
miliary tuberculosis. He was treated successfully with antituberculosis
treatment.
PMID- 26435863
TI - A Rare Case of Diffuse Alveolar Hemorrhage Secondary to Acute Pulmonary
Histoplasmosis.
AB - Diffuse alveolar hemorrhage (DAH) is a rare presentation of acute pulmonary
histoplasmosis. While histoplasmosis has been reported to cause hemoptysis and
alveolar hemorrhage in children, the English language literature lacks any adult
case reports documenting this association. We report a case of pulmonary
histoplasmosis where the initial presentation was pneumonia with a subsequent
diagnosis of DAH.
PMID- 26435864
TI - A Case of Subacute Combined Degeneration of the Spinal Cord with Infective
Endocarditis.
AB - Background. Subacute combined degeneration (SCD) is a rare cause of demyelination
of the dorsal and lateral columns of spinal cord and is a neurogenic complication
due to cobalamin deficiency. Anemia of chronic disease (ACD) occurs in patients
with acute or chronic immune activation, including infective endocarditis. It
remains to be elucidated whether ACD patients are more sensitive to suffer from
SCD. Little cases about SCD patients accompanied with ACD have been reported till
now. Here we reported a 36-year-old man with SCD with a medical history of mitral
inadequacy over 20 years, who was admitted and transported from another hospital
to our hospital due to an 8-month history of gait disturbance, lower limb
weakness and paresthesia, and loss of proprioception. Significant laboratory
results and echocardiography suggest iron deficiency anemia and infective
endocarditis (IE). The SCD diagnosis was confirmed by MRI, which showed selective
demyelination in the dorsal and lateral columns of spinal cord. In conclusion,
the ACD patients may suffer from SCD, which can be diagnosed by 3 Tesla magnetic
resonance imaging.
PMID- 26435865
TI - Didelphys Uterus: A Case Report and Review of the Literature.
AB - Background. Mullerian duct anomalies (MDAs) are congenital defects of the female
genital system that arise from abnormal embryological development of the
Mullerian ducts. A didelphys uterus, also known as a "double uterus," is one of
the least common amongst MDAs. This report discusses a case of didelphys uterus
that successfully conceived, carried her pregnancy to term, and delivered
vaginally without any significant complications. Case. Patient is a 29-year-old
G2P0010 from Bangladesh, initially came a year prior in her first pregnancy, with
spontaneous abortion (SAB). Pelvic Sonogram at that time showed a diagnosis of
bicornuate versus didelphys uterus. There were no renal anomalies on subsequent
abdominal CT scan. Patient presented with the second pregnancy and had
uncomplicated prenatal care and did not have signs of preterm labor; fetus showed
appropriate growth and the pregnancy was carried in the left uterus. Patient
presented at 38 4/7 wks with Premature Rupture of Membrane and underwent
induction of labor with Cytotec. Antibiotics were started for chorioamnionitis.
Patient had a vaginal delivery with left mediolateral episiotomy and complete
tear of vaginal septum. Third stage of labor was complicated with retained
placenta, which was removed manually in the operating room with total EBL of 600
cc.
PMID- 26435866
TI - Persistent Notochord in a Fetus with COL2A1 Mutation.
AB - Multiple anomalies including micromelia, poor mineralization of the vertebrae,
and a persistent notochord were identified on second trimester ultrasound in a
fetus with a COL2A1 mutation. To our knowledge, this represents the first case of
a persistent notochord associated with a COL2A1 mutation in humans. In this case
report, we describe ultrasound and postmortem findings and review the
pathogenesis associated with a persistent notochord.
PMID- 26435867
TI - Traumatic Death due to Simultaneous Double Spine Fractures in Patient with
Ankylosing Spondylitis.
AB - The aim of this study is to report the rare occurrence of simultaneous double
spine fractures in a patient with progressive ankylosing spondylitis (AS). An 82
year-old male with established AS had low-energy falls. He had sustained
simultaneous double spine fractures and died. Plain radiographs of the cervical
spine were unremarkable in detecting a cervical spine fracture in a patient with
AS and a spinal cord injury following a fall. CT scan showed a displaced fracture
at the C6/C7 with American Spinal Injury Association-A spinal cord injury and
displaced fracture at L1. The cause of death was determined to be upper spinal
cord injury caused by cervical spinal fracture and dislocation that were
facilitated by spinal rigidity from AS. This case report illustrates the
importance of obtaining a detailed medical history and thorough imaging study
when investigating deaths, including nonfatal conditions, such as AS.
Furthermore, it shows the value of entire spine CT scan in the evaluation of the
mechanism, further spine fractures, and manner of death. Despite the occurrence
of spine fracture in AS patients, simultaneous double or multiple spine fractures
are extremely rare and can be missed. Care should be taken for the further spine
fracture in the entire spine in patient with AS.
PMID- 26435868
TI - Pediatric Ramsay Hunt Syndrome: Analysis of Three Cases.
AB - Ramsay Hunt syndrome (RHS) is a disorder characterized by herpetic eruptions on
the auricle, facial paralysis, and vestibulocochlear dysfunction and is
attributed to varicella zoster virus (VZV) infection in the geniculate ganglion.
Although it is a common cause of acute peripheral facial paralysis, children are
not usually affected. The diagnosis is based on history and physical findings.
Treatment of RHS uses a combination of high-dose corticosteroids and acyclovir.
This paper presents three cases diagnosed as RHS in the pediatric age group in
association with the literature review. The aim of this paper is to emphasize the
importance of careful examination and early initiation of therapy in suspected
cases of RHS.
PMID- 26435869
TI - Cardiac Tamponade Associated with the Presentation of Anaplastic Large Cell
Lymphoma in a 2-Year-Old Child.
AB - The anaplastic large cell lymphoma is a rare entity in pediatric patients. We
present an unusual case of pericardial involvement, quite uncommon as extranodal
presentation of this type of disorder, that provoked a life-risk situation
requiring an urgent pericardiocentesis. To our knowledge, this is the first
report on a child with pericardial involvement without an associated cardiac mass
secondary to anaplastic large cell lymphoma in pediatric age. We report the case
of a 21-month-old Caucasian male infant with cardiac tamponade associated with
the presentation of anaplastic large cell lymphoma. Initially, the child
presented with 24-day prolonged fever syndrome, cutaneous lesions associated with
hepatomegaly, inguinal adenopathies, and pneumonia. After a 21-day asymptomatic
period, polypnea and tachycardia were detected in a clinical check-up. Chest X
ray revealed a remarkable increase of the cardiothoracic index. The anaplastic
large cell lymphoma has a high incidence of extranodal involvement but myocardial
or pericardial involvements are rare. For this reason, we recommend a close
monitoring of patients with a differential diagnosis of anaplastic large cell
lymphoma.
PMID- 26435870
TI - Paravertebral and Retroperitoneal Vascular Tumour Presenting with Kasabach
Merritt Phenomenon in Childhood, Diagnosed with Magnetic Resonance Imaging.
AB - Kasabach-Merritt phenomenon (KMP) is characterized by vascular tumour and
consumptive coagulopathy with life-threatening thrombocytopenia, prolonged
prothrombin time and partial thromboplastin time, hypofibrinogenemia, and the
presence of high fibrin split products. We report a case of 3-year-old boy with
local aggressive vascular lesions associated with KMP. Magnetic resonance imaging
revealed an extensive lesion at paravertebral and retroperitoneal regions that
was infiltrating vertebrae. Although we did not get any response to steroid or
propranolol treatment, partial response was observed radiologically with
interferon-alpha treatment. Unfortunately, the patient died because of the
uncontrolled consumptive coagulopathy that led to intracranial hemorrhage which
was caused by huge knee hematoma after minor trauma.
PMID- 26435871
TI - Severe Pulmonary Arterial Hypertension: Comprehensive Evaluation by Magnetic
Resonance Imaging.
AB - Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary
artery (PA) pressure, which negatively affects the right ventricular (RV)
function. This report shows a patient with severe PAH, on whom a comprehensive
MRI exam was performed to evaluate both PA and RV. New imaging sequences were
implemented for obtaining additional parameters about the patient's condition.
The results show the capabilities of the developed exam of providing complete
picture of the cardiovascular system in PAH, which helps the physician optimize
treatment.
PMID- 26435872
TI - Anastomosing Haemangioma of the Kidney Involving a Segmental Branch of the Renal
Vein.
AB - Anastomosing variant of capillary haemangioma is a rare and recently described
vascular tumour with a proclivity for the genitourinary tract. Here we present
the case of a 64-year-old man with incidental finding of 3.4 cm renal mass on CT
who had laparoscopic nephrectomy with a good postoperative recovery.
Histopathological diagnosis of anastomosing haemangioma of the kidney was made
and the patient was followed up for 10 months without evidence of tumour
recurrence.
PMID- 26435873
TI - Xanthogranulomatous Pyelonephritis of a Lower Pole Moiety in a Duplicated
Collecting System Kidney.
AB - Xanthogranulomatous pyelonephritis (XGP) is a destructive inflammatory process
which is frequently caused by recurrent urinary tract infections or chronic
obstruction by kidney stones. We present a 56-year-old female with an extensive
retroperitoneal urinoma and xanthogranulomatous pyelonephritis of the lower pole
moiety in a kidney with a duplicated collecting system due to obstructive
nephrolithiasis. After drainage of the urinoma, the patient underwent a
definitive lower pole heminephrectomy with preservation of the functional upper
pole. We review important clinical features of xanthogranulomatous pyelonephritis
and considerations for surgery on a duplicated kidney.
PMID- 26435874
TI - Palpable Penile Metastases: A Bizarre Presentation of Rectal Adenocarcinoma.
AB - Metastasis to the penis is an uncommon occurrence, with only about 370 cases
reported in the literature to date. The majority of the primary tumors are
genitourinary in origin. We report on a patient with undiagnosed disseminated
rectal adenocarcinoma, who first presented with lesions of the corporal bodies. A
review of the literature indicates that corporeal metastasis as an initial
presentation of malignancy is an extremely rare occurrence and carries a very
poor prognosis.
PMID- 26435875
TI - Calcification Characteristics of Low-Flow Low-Gradient Severe Aortic Stenosis in
Patients Undergoing Transcatheter Aortic Valve Replacement.
AB - Low-flow low-gradient severe aortic stenosis (LFLGAS) is associated with worse
outcomes. Aortic valve calcification patterns of LFLGAS as compared to non-LFLGAS
have not yet been thoroughly assessed. 137 patients undergoing transcatheter
aortic valve replacement (TAVR) with preprocedural multidetector computed
tomography (MDCT) and postprocedural transthoracic echocardiography were
enrolled. Calcification characteristics were assessed by MDCT both for the total
aortic valve and separately for each leaflet. 34 patients had LFLGAS and 103 non
LFLGAS. Total aortic valve calcification volume (p < 0.001), mass (p < 0.001),
and density (p = 0.004) were lower in LFLGAS as compared to non-LFLGAS patients.
At 30-day follow-up, mean transaortic pressure gradients and more than mild
paravalvular regurgitation did not differ between groups. In conclusion, LFLGAS
and non-LFLGAS express different calcification patterns which, however, did not
impact on device success after TAVR.
PMID- 26435876
TI - Single Center Retrospective Analysis of Conventional and Radial TIG Catheters for
Transradial Diagnostic Coronary Angiography.
AB - Current guidelines favor the radial approach for coronary angiography. Therefore,
specialty radial diagnostic catheters were designed to engage both coronary
arteries with a single device. However, it is unclear if single catheters are
superior to conventional catheters. A retrospective analysis was performed of
consecutive right radial coronary angiographies to determine catheter use,
fluoroscopy time, radiation dosage, and consumption of contrast. Procedures were
performed with a single TIG catheter or conventional catheters (CONV). Procedures
with coronary artery bypass grafts or ventricular angiographies were excluded.
273 transradial procedures were performed successfully. 95 procedures were
performed with CONV and 178 procedures with a TIG. Crossover to additional
catheters was higher in TIG (15.2%) compared to CONV (5.3%, p = 0.02).
Fluoroscopy time was comparable between CONV and TIG, without crossover (2.2 +/-
1.2 min versus 2.3 +/- 1.2 min; n.s.), however, greater in the case of crossover
for CONV (5.8 +/- 0.7) and TIG (7.6 +/- 3.0; p = 0.0001). Radiation dosage was
similar in CONV and the TIG, without crossover (1419 +/- 1075, cGy*cm(2) versus
1690 +/- 1138; n.s.), however, greater for CONV (2374 +/- 620) and TIG (3733 +/-
2281, p = 0.05) with crossover. Overall, the amount of contrast was greater in
TIG (56 +/- 13 mL) versus CONV (48 +/- 3 mL; p = 0.0003). CONV femoral catheters
may be the primary choice for radial approach.
PMID- 26435877
TI - Tuberculosis of the Penis: A Review of the Literature.
AB - Background. Tuberculosis of the penis (TBP) is rare. Aim. To review the
literature. Method. Various internet data bases were searched. Literature Review.
TBP could be primary or secondary, may develop following circumcision performed
by a person who had pulmonary Tb, and may be transmitted to the penis from
ejaculation, contamination from clothing, or from contact with endometrial
secretions, following an earlier pulmonary Tb or Tb elsewhere. TBP presents with
a painless/painful small nodule, ulcer, mass on penis which gradually enlarges,
and induration/swelling of penis, with or without erectile dysfunction. Inguinal
lymph nodes may or may not be palpable. The patient's voiding is normal. There
may or may not be history of circumcision, pulmonary Tb, and BCG immunization.
TBP mimics penile carcinoma, granulomatous syphilis penile ulcer, genital herpes
simplex, granuloma inguinale, and HIV infection. Diagnosis is established by
microscopic examination finding of granulomas +/-AFB in penile discharge or
biopsy of lesion or culture of Tb organism from discharge or biopsy specimens or
positive Elisa serology/PCR for Tb. PTBs respond to first- or 2nd-line anti-Tb 6
month treatment. Close contacts should be screened. Extrapulmonary Tb should be
excluded. Conclusions. Clinicians should consider possibility of PTB in cases of
penile lesions and erectile failure.
PMID- 26435878
TI - SPECTROSCOPY/MICROSCOPY: Nonlinear Raman microscopy eyes clinical application.
AB - Nonlinear Raman microscopy is an emerging technique in biomedical imaging. An
inexpensive prototype system, based on coherent anti-Stokes Raman scattering
(CARS), demonstrates value for real-time, minimally invasive chemical analysis of
cells and tissues. It overcomes drawbacks of both Raman and CARS, and in doing so
demonstrates potential for clinical application-including blood analysis and
breast cancer detection.
PMID- 26435879
TI - The Process of Adapting the Evidence-Based Treatment for Tobacco Dependence for
Smokers of Lower Socioeconomic Status.
AB - INTRODUCTION: Tobacco use is the leading cause of preventable death and disease
and contributes significantly to socioeconomic health disparities. The prevalence
of smoking among individuals of lower socioeconomic status (SES) in the US, many
of whom are African American (AA), is three to four times greater than the
prevalence of smoking among individuals of higher SES. The disparity in tobacco
dependence treatment outcomes between lower and higher SES smokers contributes to
tobacco-related health disparities and calls for adapting evidence-based
treatment to more fully meet the needs of lower SES smokers. AIMS: We sought to
adapt the evidence-based treatment for tobacco dependence using recommended
frameworks for adapting evidence-based treatments. METHODS: We systematically
applied the recommended steps for adapting evidence-based treatments described by
Barrera and Castro and Lau. The steps included information gathering, preliminary
adaptation design, preliminary adaptation tests, and adaptation refinement. We
also applied the PEN-3 Model for incorporating AA values and experiences into
treatment approaches and a community-engaged approach. RESULTS/FINDINGS: Findings
from each step in the process contributed to the results. The final results were
incorporated into a revised treatment called the RITCh Study Tobacco Dependence
Treatment Manual and Toolkit. CONCLUSIONS: To our knowledge, this is the first
adaptation of evidence-based treatment for tobacco dependence that has
systematically applied these recommended frameworks. The efficacy of the
treatment to reduce treatment outcome disparities is now being examined in a
randomized controlled trial in which the revised treatment is being compared with
a standard, individualized cognitive-behavioral approach.
PMID- 26435880
TI - Cystathionine Levels in Patients With Huntington Disease.
AB - BACKGROUND: Recently a profound depletion of cystathionine gamma-lyase (CSE), the
principal enzyme involved in the generation of cysteine from cystathionine, was
shown in Huntington disease (HD) patients and several transgenic HD mouse models.
We therefore hypothesized that blood and urine cystathionine levels may be
increased in HD patients and that this increase might correlate with disease
progression. METHODS: We measured concentrations of cystathionine as well as 22
other amino acids in fasting plasma and 24-h urine samples of nine early-stage HD
patients and nine age, sex, and body mass index matched controls. RESULTS: There
were no significant differences in the plasma or urine concentrations of
cystathionine or any other amino acid between HD patients and controls.
CONCLUSION: We found no evidence for changes in plasma or urine concentrations of
cystathionine in early-stage HD patients. Therefore, cystathionine levels are
unlikely to be useful as a state biomarker in HD.
PMID- 26435881
TI - Mobile genetic elements are involved in bacterial sociality.
AB - Mobile genetic elements in bacteria are enriched in genes participating in social
behaviors, suggesting an evolutionary link between gene mobility and social
evolution. Cooperative behaviors, like the production of secreted public good
molecules, are susceptible to the invasion of non-cooperative individuals, and
their evolutionary maintenance requires mechanisms ensuring that benefits are
directed preferentially to cooperators. In order to investigate the reasons for
the mobility of public good genes, we designed a synthetic bacterial system where
we control and quantify the transfer of public good production genes. In our
recent study, we have experimentally shown that horizontal transfer helps
maintain public good production in the face of both non-producer organisms and
non-producer plasmids. Transfer spreads genes to neighboring cells, thus
increasing relatedness and directing a higher proportion of public good benefits
to producers. The effect is the strongest when public good genes undergo
epidemics dynamics, making horizontal transfer especially relevant for pathogenic
bacteria that repeatedly infect new hosts and base their virulence on costly
public goods. The promotion of cooperation may be a general consequence of
horizontal gene transfer in prokaryotes. Our work has an intriguing parallel,
cultural transmission, where horizontal transfer, such as teaching, may
preferentially promote cooperative behaviors.
PMID- 26435882
TI - Household Wealth in China.
AB - With new nationwide longitudinal survey data now available from the China Family
Panel Studies (CFPS), we study the level, distribution, and composition of
household wealth in contemporary China. We find that the wealth Gini coefficient
of China was 0.73 in 2012. The richest 1 percent owned more than one-third of the
total national household wealth, while the poorest 25 percent owned less than 2
percent. Housing assets, which accounted for over 70 percent, were the largest
component of household wealth. Finally, the urban-rural divide and regional
disparities played important roles in household wealth distribution, and
institutional factors significantly affected household wealth holdings, wealth
growth rate, and wealth mobility.
PMID- 26435883
TI - Period homolog LIN-42 regulates miRNA transcription to impact developmental
timing.
AB - Two recent studies by Van Wynsberghe et al. and Perales et al. in the nematode C.
elegans have demonstrated a new function of the Period protein homolog LIN-42 in
negatively regulating microRNA (miRNA) biogenesis at the transcriptional level.
LIN-42 is a complex gene with 4 isoforms and multiple functions including the
regulation of molting, developmental timing and entry into dauer. These recent
studies uncover an additional function of LIN-42 as a negative regulator of miRNA
transcription. Approximately 95% of miRNAs present in eggs and 33% of miRNAs
present in L4 stage worms were upregulated in lin-42 mutant worms relative to
wild type (WT) worms, suggesting that LIN-42 globally regulates miRNA biogenesis.
Expression from both a let-7 miRNA and a lin-4 miRNA transcriptional reporter
were enhanced in the absence of lin-42. Additionally, chromatin
immunoprecipitation followed by high throughput sequencing (ChIP-seq) of late
larval stage worms showed that LIN-42 bound the let-7 promoter, suggesting that
LIN-42 affects mature miRNA levels by inhibiting their transcription. In addition
to miRNAs, LIN-42 also predominantly bound to the promoters of many diverse
protein-coding genes. These findings support the action of LIN-42 at multiple
points within the heterochronic and other regulatory pathways to impact a
multitude of functions including developmental timing.
PMID- 26435884
TI - Robust tracking and quantification of C. elegans body shape and locomotion
through coiling, entanglement, and omega bends.
AB - The behavior of the well-characterized nematode, Caenorhabditis elegans (C.
elegans), is often used to study the neurologic control of sensory and motor
systems in models of health and neurodegenerative disease. To advance the
quantification of behaviors to match the progress made in the breakthroughs of
genetics, RNA, proteins, and neuronal circuitry, analysis must be able to extract
subtle changes in worm locomotion across a population. The analysis of worm
crawling motion is complex due to self-overlap, coiling, and entanglement. Using
current techniques, the scope of the analysis is typically restricted to worms to
their non-occluded, uncoiled state which is incomplete and fundamentally biased.
Using a model describing the worm shape and crawling motion, we designed a
deformable shape estimation algorithm that is robust to coiling and entanglement.
This model-based shape estimation algorithm has been incorporated into a
framework where multiple worms can be automatically detected and tracked
simultaneously throughout the entire video sequence, thereby increasing
throughput as well as data validity. The newly developed algorithms were
validated against 10 manually labeled datasets obtained from video sequences
comprised of various image resolutions and video frame rates. The data presented
demonstrate that tracking methods incorporated in WormLab enable stable and
accurate detection of these worms through coiling and entanglement. Such
challenging tracking scenarios are common occurrences during normal worm
locomotion. The ability for the described approach to provide stable and accurate
detection of C. elegans is critical to achieve unbiased locomotory analysis of
worm motion.
PMID- 26435885
TI - Proteomic identification of germline proteins in Caenorhabditis elegans.
AB - Sexual reproduction involves fusion of 2 haploid gametes to form diploid
offspring with genetic contributions from both parents. Gamete formation
represents a unique developmental program involving the action of numerous
germline-specific proteins. In an attempt to identify novel proteins involved in
reproduction and embryonic development, we have carried out a proteomic
characterization of the process in Caenorhabditis elegans. To identify candidate
proteins, we used 2D gel electrophoresis (2DGE) to compare protein abundance in
nucleus-enriched extracts from wild-type C. elegans, and in extracts from mutant
worms with greatly reduced gonads (glp-4(bn2) worms reared at 25 degrees C); 84
proteins whose abundance correlated with germline presence were identified. To
validate candidates, we used feeding RNAi to deplete candidate proteins, and
looked for reduction in fertility and/or germline cytological defects. Of 20
candidates so screened for involvement in fertility, depletion of 13 (65%) caused
a significant reduction in fertility, and 6 (30%) resulted in sterility (<5 % of
wild-type fertility). Five of the 13 proteins with demonstrated roles in
fertility have not previously been implicated in germline function. The high
frequency of defects observed after RNAi depletion of candidate proteins suggests
that this approach is effective at identifying germline proteins, thus
contributing to our understanding of this complex organ.
PMID- 26435886
TI - The C. elegans UNC-23 protein, a member of the BCL-2-associated athanogene (BAG)
family of chaperone regulators, interacts with HSP-1 to regulate cell attachment
and maintain hypodermal integrity.
AB - Mutations in the unc-23 gene in the free-living nematode, Caenorhabditis elegans
result in detachment and dystrophy of the anterior body wall musculature and a
bent-head phenotype when grown on solid substrate. We have determined that the
unc-23 gene product is the nematode ortholog of the human BAG-2 protein, a member
of the Bcl-2 associated athanogene (BAG) family of molecular chaperone
regulators. We show that a functional GFP-tagged UNC-23 protein is expressed
throughout development in several tissues of the animal, including body wall
muscle and hypodermis, and associates with adhesion complexes and attachment
structures within these 2 tissues. In humans, the BAG protein family consists of
6 members that all contain a conserved 45 amino acid BAG domain near their C
termini. These proteins bind to and modulate the activity of the ATPase domain of
the heat shock cognate protein 70, Hsc70. We have isolated missense mutations in
the ATPase domain of the C. elegans heat shock 70 protein, HSP-1 that suppress
the phenotype exhibited by unc-23(e25) mutant hermaphrodites and we show that UNC
23 and HSP-1 interact in a yeast-2-hybrid system. The interaction of UNC-23 with
HSP-1 defines a role for HSP-1 function in the maintenance of muscle attachment
during development.
PMID- 26435887
TI - New links between protein N-terminal acetylation, dauer diapause, and the
insulin/IGF-1 signaling pathway in Caenorhabditis elegans.
AB - Protein N-terminal acetylation is a widespread posttranslational modification in
eukaryotes that is catalyzed by N-terminal acetyltransferases (NATs). The
biochemical activity of NATs has been characterized extensively, whereas the
biological function of NATs is only beginning to be defined. Here we comment on
recent progress in understanding the function of NAT activity in C. elegans based
on the characterization of natc-1 by Warnhoff et al. (2014) and daf-31 by Chen et
al. (2014).(1,2) natc-1 encodes an auxiliary subunit of the NatC complex and
modulates stress tolerance, dauer entry, and adult lifespan. daf-31 encodes the
catalytic subunit of the NatA complex and affects dauer entry, dauer formation,
and adult lifespan. The analysis of these genes and genetic studies of NATs in
other organisms suggests protein N-terminal acetylation plays an evolutionarily
conserved role in promoting growth and development and inhibiting stress
resistance. Furthermore, we propose that NATs may regulate growth and development
in response to external cues such as nutrient deprivation and other physiologic
stresses.
PMID- 26435888
TI - Factors Associated with Colorectal Cancer Screening among Younger African
American Men: A Systematic Review.
AB - Of cancers affecting both men and women, colorectal cancer (CRC) is the second
leading cancer killer among African Americans in the U.S. Compared to White men,
African American men have incidence and mortality rates 25% and 50% higher from
CRC. Despite the benefits of early detection and the availability of effective
screening, most adults over age 50 have not undergone testing, and disparities in
colorectal cancer screening (CRCS) persist. Owing to CRC's high incidence and
younger age at presentation among African American men, CRCS is warranted at age
45 rather than 50. However, the factors influencing young adult (i.e., age < 50)
African American men's intention to screen and/or their CRCS behaviors has not
been systematically assessed. To assess whether the factors influencing young
adult African American men's screening intentions and behaviors are changeable
through structured health education interventions, we conducted a systematic
review, with the two-fold purpose of: (1) synthesizing studies examining African
American men's knowledge, beliefs, and behaviors regarding CRCS; and (2)
assessing these studies' methodological quality. Utilizing Garrard's Matrix
Method, a total of 28 manuscripts met our inclusion/exclusion criteria: 20
studies followed a non-experimental research design, 4 comprised a quasi
experimental design, and 4, an experimental design. Studies were published
between 2002 and 2012; the majority, between 2007 and 2011. The factors most
frequently assessed were behaviors (79%), beliefs (68%), and knowledge (61%) of
CRC and CRCS. Six factors associated with CRC and CRCS emerged: previous CRCS,
CRC test preference, perceived benefits, perceived barriers, CRC/CRCS knowledge,
and physician support/recommendation. Studies were assigned a methodological
quality score (MQS - ranging from 0 to 21). The mean MQS of 10.9 indicated these
studies were, overall, of medium quality and suffered from specific flaws.
Alongside a call for more rigorous research, this review provides important
suggestions for practice and culturally relevant interventions.
PMID- 26435889
TI - Randomized sham controlled trial of cranial microcurrent stimulation for symptoms
of depression, anxiety, pain, fatigue and sleep disturbances in women receiving
chemotherapy for early-stage breast cancer.
AB - PURPOSE: Women with breast cancer may experience symptoms of depression, anxiety,
pain, fatigue and sleep disturbances during chemotherapy. However, there are few
modalities that address multiple, commonly occurring symptoms that may occur in
individuals receiving cancer treatment. Cranial electrical stimulation (CES) is a
treatment that is FDA cleared for depression, anxiety and insomnia. CES is
applied via electrodes placed on the ear that deliver pulsed, low amplitude
electrical current to the head. METHODS: This phase III randomized, sham
controlled study aimed to examine the effects of cranial microcurrent stimulation
on symptoms of depression, anxiety, pain, fatigue, and sleep disturbances in
women receiving chemotherapy for early-stage breast cancer. Patients were
randomly assigned to either an actual or sham device and used the device daily
for 1 h. The study was registered at clinicaltrials.gov, NCT00902330. RESULTS:
The sample included N = 167 women with early-stage breast cancer. Symptom
severity of depression, anxiety, and fatigue and sleep disturbances were
generally mild to moderate. Levels of pain were low. Anxiety was highest prior to
the initial chemotherapy and decreased over time. The primary outcome assessment
(symptoms of depression, anxiety, fatigue, pain, sleep disturbances) revealed no
statistically significant differences between the two groups, actual CES vs.
sham. CONCLUSION: In this study, women receiving chemotherapy for breast cancer
experienced multiple symptoms in the mild to moderate range. Although there is no
evidence for the routine use of CES during the chemotherapy period for symptom
management in women with breast cancer, further symptom management modalities
should be evaluated to mitigate symptoms of depression, anxiety, fatigue, pain
and sleep disturbances over the course of chemotherapy.
PMID- 26435890
TI - A Markov chain Monte Carlo (MCMC) methodology with bootstrap percentile estimates
for predicting presidential election results in Ghana.
AB - Although, there exists numerous literature on the procedure for forecasting or
predicting election results, in Ghana only opinion poll strategies have been
used. To fill this gap, the paper develops Markov chain models for forecasting
the 2016 presidential election results at the Regional, Zonal (i.e. Savannah,
Coastal and Forest) and the National levels using past presidential election
results of Ghana. The methodology develops a model for prediction of the 2016
presidential election results in Ghana using the Markov chains Monte Carlo (MCMC)
methodology with bootstrap estimates. The results were that the ruling NDC may
marginally win the 2016 Presidential Elections but would not obtain the more than
50 % votes to be declared an outright winner. This means that there is going to
be a run-off election between the two giant political parties: the ruling NDC and
the major opposition party, NPP. The prediction for the 2016 Presidential run-off
election between the NDC and the NPP was rather in favour of the major opposition
party, the NPP with a little over the 50 % votes obtained.
PMID- 26435891
TI - Occurrence and prevalence of Cronobacter spp. in plant and animal derived food
sources: a systematic review and meta-analysis.
AB - Cronobacter species are motile, non-spore forming, Gram negative emerging
opportunistic pathogens mostly associated with bacteremia, meningitis,
septicemia, brain abscesses and necrotizing enterocolitis in infected neonates,
infants and immunocompromised adults. Members of the genus Cronobacter are
previously associated with powdered infant formula although the main reservoir
and routes of contamination are yet to be ascertained. This study therefore aim
to summarize occurrence and prevalence of Cronobacter spp. from different food
related sources. A retrospective systematic review and meta-analysis of peer
reviewed primary studies reported between 2008 and 2014 for the occurrence and
prevalence of Cronobacter spp. in animal and plant related sources was conducted
using "Cronobacter isolation", "Cronobacter detection" and "Cronobacter
enumeration" as search terms in the following databases: Web of Science (Science
Direct) and ProQuest. Data extracted from the primary studies were then analyzed
with meta-analysis techniques for effect rate and fixed effects was used to
explore heterogeneity between the sources. Publication bias was evaluated using
funnel plot. A total of 916 articles were retrieved from the data bases of which
28 articles met inclusion criteria. Cronobacter spp. could only be isolated from
103 (5.7 %) samples of animal related food while 123 (19 %) samples of plant
related food samples harbors the bacteria. The result of this study shows that
occurrence of Cronobacter was more prevalent in plant related sources with
overall prevalence rate of 20.1 % (95 % CI 0.168-0.238) than animal originated
sources with overall prevalence rate of 8 % (95 % CI 0.066-0.096). High
heterogeneity (I (2) = 84) was observed mostly in plant related sources such as
herbs, spices and vegetables compared to animal related sources (I (2) = 82). It
could be observed from this study that plant related sources serve as reservoir
and contamination routes of Cronobacter spp.
PMID- 26435892
TI - Amino acids in sandal (Santalum album L) with special reference to cis-4-hydroxy
l-proline and sym. homospermidine.
AB - Sandal (Santalum album L) contains several interesting amino acids and amines
which are not seen in other plants. This includes cis-4-hydroxy-l-proline in free
form in leaves, flowers and seeds while trans-4-hydroxy-l-proline in bound form.
Traces of 3, 4 dehydroproline is also detected in sandal leaves. Biosynthesis of
cis-4-hydroxy proline indicates that hydroxylation taken place at proline present
in peptidyl form especially bound to glutamic acid and aspartic acid.
Pyrrolizidine-2-carboxylic acid an interesting isatin positive heterocyclic
compound is also present in sandal leaves. Sandal also contains sym.
homospermidine which is not present in any other plants till today. Biosynthesis
of sym. homospermidine goes by a unique pathway of putrescine oxidation, Schiff
base formation, condensation and reduction. Moreover sandal leaves contain gamma
glutamyl derivative of the lachrymatory precursor of onion, gamma-glutamyl-S
propenyl cysteine superoxide. This review summarizes the studies on the amino
acids in sandal.
PMID- 26435893
TI - IgA nephropathy in Brazil: apropos of 600 cases.
AB - IgA nephropathy (IgAN) is th e commonest primary glomerular disease worldwide.
Studies on its prevalence in Brazil are however scarce. Databases and clinical
records from 10 reference centres were retrospectively reviewed. Clinical and
laboratory features at the moment of the biopsy were retrieved (age, gender,
presence of hematuria, serum creatinine [mg/dL], proteinuria [g/24 h]). Renal
biopsy findings were classified according to Haas single grade classification
scheme and the Oxford Classification of IgAN. 600 cases of IgAN were identified,
of which 568 (94.7 %) were on native kidneys. Male to female ratio was 1.24:1.
Patients averaged 32.76 +/- 15.12 years old (range 4-89, median 32). Proteinuria
and hematuria were observed, respectively in 56.63 and 72.29 % of patients. The
association of both these findings occurred in 37.95 % of the cases. Serum
creatinine averaged 1.65 +/- 0.67 mg/dL (median 1.5 mg/dL) at diagnosis.
Segmental sclerosis and mesangial hypercellularity were the main glomerular
findings (47.6 and 46.2 %) The commonest combination by Oxford Classification of
IgAN, was M0 E0 S0 T0 (22.4 %). Chronic tubulo-interstitial lesions with an
extension wider than 25 % of the renal cortex could be identified in 32.2 % of
the cases. Tubular atrophy and interstitial fibrosis were more strongly
associated with higher 24-h proteinuria and serum creatinine levels. Segmental
sclerosis (S1) showed a stronger tendency of association with the presence of
tubulo-interstitial lesions (T1 and T2) than other glomerular variables. To the
best of our knowledge this is the largest series of IgAN in Brazil. It depicts
the main biopsy findings and their possible clinical correlates. Our set of data
is comparable to previous reports.
PMID- 26435894
TI - Binding interaction of a novel fluorophore with serum albumins: steady state
fluorescence perturbation and molecular modeling analysis.
AB - Fluorescence emission and anisotropy are widely used to measure the binding
parameters and kinetic behavior of reactions that cause a change in the
rotational time of a fluorescent molecule. We report here fluorescence emission
and anisotropy behavior of a newly synthesized novel naphthalene base fluorophore
(methyl 3-[(6-{[2-(tert-butoxy)-2-oxoethyl] (4-methoxyphenyl)amino}naphthalen-2
yl)formamido]propanoate) in several solution conditions including its binding to
human and bovine serum albumin proteins both in their native and denatured
states. The fluorescence yield of the compound substantially increased inside
hydrophobic protein surface and ~30 nm decrease in Stokes' shift, compared to
aqueous solution, was observed. Shift in fluorescence excitation peak position
from the absorption peak of the molecule was ~8 nm in protein solution. This
indicated possible alteration of excited state geometry of the compound by the
globular fold of albumins. In addition, we measured the steady state fluorescence
anisotropy of the molecule to evaluate several thermodynamic parameters and the
results suggested the binding was energetically favorable. The measured DeltaG
degrees was ~-30 kJ mol(-1) and the derived dissociation constant was ~10(-6) M.
The molecular docking analysis further highlighted the nonspecific association of
the compound with the proteins and hydrophobic forces may have a significant role
in the binding processes. Under the denatured condition of the protein, the
compound lost its binding efficacy and reduction in fluorescence intensity was
observed. Thus, the molecule appears as a new fluorescence probe to report the
nature of its binding site in terms of increased fluorescence quantum yield and
decreased Stokes' shift. It can also report the changes in the binding site due
to global change in protein structure such as unfolding/misfolding often linked
to several human disorder. Further it could be useful to detect and study the
drug binding site of specific protein of interest.
PMID- 26435895
TI - Secure land tenure as prerequisite towards sustainable living: a case study of
native communities in Mantob village, Sabah, Malaysia.
AB - Sustainable livelihoods, once enjoyed by native communities, are often threatened
and in danger of extinction when new regulations and other forms of restrictions
are introduced. These restrictions are often promoted with intended purposes,
such as protecting the environment or securing resources from encroachment.
However, these acts are slowly replacing the traditional adat (customs and
traditions), which are used to define the rights attached to the use of communal
and ancestral land. This is especially true when comes to access to forest
products and land, in which native communities have used for generations. What
the natives see as legitimate and traditional use, the state sees as an
encroachment of property; and it has now become illegal to utilise these
resources. This paper presents how native communities have adapted to such
restrictions and continued to live in a sustainable manner through an adaptive
strategy that is in line with state policy changes. A combination of quantitative
and qualitative method is used to understand the dynamics of the strategy used by
the native communities to adapt to these policy changes. The findings reveal how
the natives have employed an adaptive strategy in response to state policy
changes. The lessons learned from this study can provide useful pointers as to
how state policies, in relation to highland settlements in the state of Sabah,
Malaysia, can be improved.
PMID- 26435896
TI - Secondary headache due to aspergillus sellar abscess simulating a pituitary
neoplasm: case report and review of literature.
AB - Fungal sellar abscess is rare. A 42-year-old man was admitted with 2-month
headache characterized by right peri-orbital pain. An intrasellar mass was found
to be simulated a pituitary neoplasm after magnetic resonance imaging
examination, and operated on via an endoscopic trans-sphenoidal approach. Milk
like pus and a mass of ash black mixed and necrotic material were found and
removed. Histopathology revealed numerous aspergillus hyphae. Itraconazole was
given on a dosage of 200 mg twice a day orally for 6 weeks. No recurrence was
observed during follow-up. Complete surgical resection through endoscopic trans
sphenoidal approach combined with systemic anti-fungal therapy, should be
considered as the optimal treatment.
PMID- 26435897
TI - An improved fault detection classification and location scheme based on wavelet
transform and artificial neural network for six phase transmission line using
single end data only.
AB - Restrictions on right of way and increasing power demand has boosted development
of six phase transmission. It offers a viable alternative for transmitting more
power, without major modification in existing structure of three phase double
circuit transmission system. Inspite of the advantages, low acceptance of six
phase system is attributed to the unavailability of a proper protection scheme.
The complexity arising from large number of possible faults in six phase lines
makes the protection quite challenging. The proposed work presents a hybrid
wavelet transform and modular artificial neural network based fault detector,
classifier and locator for six phase lines using single end data only. The
standard deviation of the approximate coefficients of voltage and current signals
obtained using discrete wavelet transform are applied as input to the modular
artificial neural network for fault classification and location. The proposed
scheme has been tested for all 120 types of shunt faults with variation in
location, fault resistance, fault inception angles. The variation in power system
parameters viz. short circuit capacity of the source and its X/R ratio, voltage,
frequency and CT saturation has also been investigated. The result confirms the
effectiveness and reliability of the proposed protection scheme which makes it
ideal for real time implementation.
PMID- 26435898
TI - Performance of technical trading rules: evidence from Southeast Asian stock
markets.
AB - This paper examines the profitability of technical trading rules in the five
Southeast Asian stock markets. The data cover a period of 14 years from January
2000 to December 2013. The instruments investigated are five Southeast Asian
stock market indices: SET index (Thailand), FTSE Bursa Malaysia KLC index
(Malaysia), FTSE Straits Times index (Singapore), JSX Composite index
(Indonesia), and PSE composite index (the Philippines). Trading strategies
investigated include Relative Strength Index, Stochastic oscillator, Moving
Average Convergence-Divergence, Directional Movement Indicator and On Balance
Volume. Performances are compared to a simple Buy-and-Hold. Statistical tests are
also performed. Our empirical results show a strong performance of technical
trading rules in an emerging stock market of Thailand but not in a more mature
stock market of Singapore. The technical trading rules also generate statistical
significant returns in the Malaysian, Indonesian and the Philippine markets.
However, after taking transaction costs into account, most technical trading
rules do not generate net returns. This fact suggests different levels of market
efficiency among Southeast Asian stock markets. This paper finds three new
insights. Firstly, technical indicators does not help much in terms of market
timing. Basically, traders cannot expect to buy at a relative low price and sell
at a relative high price by just using technical trading rules. Secondly,
technical trading rules can be beneficial to individual investors as they help
them to counter the behavioral bias called disposition effects which is the
tendency to sell winning stocks too soon and holding on to losing stocks too
long. Thirdly, even profitable strategies could not reliably predict subsequent
market directions. They make money from having a higher average profit from
profitable trades than an average loss from unprofitable ones.
PMID- 26435899
TI - A practical route to beta(2,3)-amino acids with alkyl side chains.
AB - Enantiopure N(Boc)-beta(3)-amino nitriles, valuable synthetic intermediates in
the multistep homologation of alpha-amino acids, were alkylated using n-BuLi as
base. Alkylations afforded easily separable, almost equimolecular mixtures of
diastereomeric N(Boc)-protected syn and anti beta(2,3)-amino nitriles. Suitable
manipulations of both cyano and amino groups eventually led to enantiopure N-
and/or C-protected beta(2,3)-amino acids. For example, methanolysis using conc.
HCl gas in MeOH, provides C-protected beta(2,3) amino acids in excellent yields.
This methodology is applied to the synthesis of a series N(Boc)-beta(2,3)-dialkyl
amino nitriles derived from l-phenylalanine, d-phenylalanine, l-valine and one C
protected beta(2,3) amino acid. We demonstrate an efficient procedure for the
preparation of anti and syn beta(2,3)-amino acids with alkyl side chains, from
alpha-amino acids in reasonable yields.
PMID- 26435900
TI - Power transformation for enhancing responsiveness of quality of life
questionnaire.
AB - We investigate the effect of power transformation of raw scores on the
responsiveness of quality of life survey. The procedure maximizes the paired t
test value on the power transformed data to obtain an optimal power range. The
parallel between the Box-Cox transformation is also investigated for the quality
of life data.
PMID- 26435901
TI - Four weeks of regular static stretching reduces arterial stiffness in middle-aged
men.
AB - Trunk flexibility may be associated with arterial stiffness in young, middle
aged, and older healthy men after adjusting for blood pressure. This study
assessed the effects of 4 weeks of regular static stretching on arterial
stiffness in middle-aged men. Sixteen healthy men (43 +/- 3 years) were assigned
to control or intervention groups (n = 8 each). The control group did not alter
their physical activity levels throughout the study period. The intervention
group participated in five supervised stretching sessions per week for 4 weeks.
Each session comprised 30 min of mild stretching that moved the major muscle
groups through the full range of motion and stretches were held three times for
20 s at the end range. Flexibility was assessed by sit-and-reach test. Arterial
stiffness was assessed by brachial-ankle pulse wave velocity (baPWV) and cardio
ankle vascular index (CAVI). Four weeks of stretching increased sit-and-reach
(Control, Pre: 31.4 +/- 2.1, Post: 30.8 +/- 2.7 vs. Intervention, Pre: 30.6 +/-
5.3, Post: 43.9 +/- 4.3 cm), and reduced baPWV (Control, Pre: 1204 +/- 25, Post:
1205 +/- 38 vs. Intervention, Pre: 1207 +/- 28, Post: 1145 +/- 19 cm/s) and CAVI
(Control, Pre: 7.6 +/- 0.3, Post: 7.5 +/- 0.3 vs. Intervention, Pre: 7.7 +/- 0.2,
Post: 7.2 +/- 0.2 units) in the intervention group. However, the change in sit
and-reach did not significantly correlate with the changes in arterial stiffness.
These findings suggest that short-term regular stretching induces a significant
reduction in arterial stiffness in middle-aged men.
PMID- 26435902
TI - Inspiratory muscle warm-up has no impact on performance or locomotor muscle
oxygenation during high-intensity intermittent sprint cycling exercise.
AB - The purpose of this study was to investigate the effect of inspiratory muscle
(IM) warm-up on performance and locomotor muscle oxygenation during high
intensity intermittent sprint cycling exercise. Ten subjects performed identical
exercise tests (10 * 5 s with 25-s recovery on a cycle ergometer) after
performing one of two different IM warm-up protocols. The IM warm-up consisted of
two sets of 30 inspiratory efforts against a pressure-threshold load equivalent
to 15 % (PLA) or 40 % (IMW) of maximal inspiratory pressure (MIP). MIP was
measured with a portable autospirometer. Peak power and percent decrease in power
were determined. Oxyhemoglobin (O2Hb) was measured using near-infrared
spectroscopy. The MIP increased relative to baseline after IMW (115 +/- 21 vs.
123 +/- 17 cmH2O, P = 0.012, ES = 0.42), but not after PLA (115 +/- 20 vs. 116 +/
17 cmH2O). Peak power (PLA: 10.0 +/- 0.6 vs. IMW: 10.2 +/- 0.5 W kg(-1)),
percent decrease in power (PLA: 13.4 +/- 5.6 vs. IMW: 13.2 +/- 5.5 %), and
changes in O2Hb levels (PLA: -10.8 +/- 4.8 vs. -10.7 +/- 4.1 MUM) did not differ
between the trials. IM function was improved by IMW. However, this did not
enhance performance or locomotor muscle oxygenation during high-intensity
intermittent sprint cycling exercise in untrained healthy males.
PMID- 26435903
TI - Relationships between physical activity and muscular strength among healthy
adults across the lifespan.
AB - The purpose of this study was to examine relationships between objective and self
report measures of physical activity and muscle strength among healthy adults
ranging in age from 20 to 91 years. Participants (n = 412) were mostly Caucasian
men (48 %) and women (52 %) 43.9 +/- 16.1 year of age with a body mass index
(BMI) of 26.4 +/- 4.8 kg/m(2). Physical activity was measured objectively with an
accelerometer and by self-report with the Paffenbarger Physical Activity
Questionnaire. Upper and lower body muscle strength were measured with an
isokinetic dynamometer and handgrip strength with a static dynamometer.
Multivariate regression assessed relationships between physical activity and
muscle strength. The strongest correlates of upper body strength including
handgrip strength were gender (r = -0.861 to -0.716), age (r = -0.445 to -0.241),
BMI (r = 0.134-0.397), and physical activity (r = 0.093-0.186). The strongest
correlates of lower body strength were gender (r = -0.772 to -0.634), age (r =
0.663 to -0.445), BMI (r = 0.160-0.266), and physical activity (r = -0.139 to
0.151). The strongest correlates of muscle strength were gender (explaining 40-74
% of the variance), age (6-44 %), and BMI (2-16 %), while physical activity
correlations were weaker (1-3 %). Conflict surrounding the influence of a
physically active lifestyle on muscle strength with age may be due to the
stronger influences of other factors that supersede those of physical activity
whether measured objectively or by self-report methods.
PMID- 26435904
TI - Embryonic and mature astrocytes exert different effects on neuronal growth in rat
ventral mesencephalic slice cultures.
AB - One obstacle with grafting of dopamine neurons in Parkinson's disease is the
insufficient ability of the transplant to reinnervate the host striatum. Another
issue is the prospective interaction between the donor fetal tissue and the adult
astrocytes of the host. To study nerve fiber growth and its interaction with
immature/mature astrocytes, ventral mesencephalic (VM) organotypic rat tissue
cultures from embryonic days (E) 12, E14, and E18 were studied up to 35 days in
vitro (DIV), and co-cultures of E14 VM tissue and mature green fluorescent
protein (GFP)-positive astrocytes were performed. Generally, nerve fibers grew
from the tissue slice either in association with a monolayer of migrated
astroglia surrounding the tissue (glial-associated), or distal to the astroglia
as non-glial-associated outgrowth. The tyrosine hydroxylase (TH)-positive glial
associated nerve fiber outgrowth reached a plateau at 21 DIV in E12 and E14
cultures. In E18 cultures, TH-positive neurons displayed short processes and
migrated onto the astrocytes. While the non-glial-associated nerve fiber
outgrowth dominated the E14 cultures, it was found absent in E18 cultures. The
GFP-positive cells in the VM and GFP-positive astrocyte co-cultures were
generally located distal to the monolayer of migrated fetal astrocytes, a few GFP
positive cells were however observed within the astrocytic monolayer. In those
cases TH-positive neurons migrated towards the GFP-positive cells. Both the non
glial- and glial-associated nerve fibers grew onto the GFP-positive cells. Taken
together, the glial-associated growth has limited outgrowth compared to the non
glial-associated nerve fibers, while none of the outgrowth types were hampered by
the mature astrocytes.
PMID- 26435905
TI - Activation of oxidative carbon metabolism by nutritional enrichment by
photosynthesis and exogenous organic compounds in the red alga Cyanidioschyzon
merolae: evidence for heterotrophic growth.
AB - Respiration is an important process in photosynthetic organisms, as it is in
other organisms, for the supply of ATP and metabolites required for biosynthesis.
Furthermore, individual enzymatic activity is subject to regulation by metabolic
intermediates in glycolysis and the citric acid cycle. However, little is known
about how glycolysis or catabolism are related to photosynthetic activity or
accumulation of photosynthetic products. We previously developed a flat-plate
culture apparatus assembled from materials commonly used for gel electrophoresis,
which enables high-density culture of the unicellular red alga Cyanidioschyzon
merolae. In this study, a stationary dense culture of C. merolae, when re
activated in this culture apparatus, exhibited an accumulation of
photosynthetically produced starch. We demonstrated that respiratory activity
increased during the culture period, while photosynthetic activity remained
constant. Gene expression analysis revealed that the genes involved in cytosolic
glycolysis and the citric acid cycle were selectively activated, compared to the
genes for the oxidative pentose phosphate pathway and the Calvin-Benson cycle.
Measurements of the respiratory rate after addition of various organic substances
showed that C. merolae can utilize almost any exogenous organic compound as a
respiratory substrate, although the effectiveness of each compound was dependent
on the culture time in the flat-plate culture, suggesting that glycolysis was
rate-limiting to respiration, and its activity depended on the level of
photosynthetic products within the cells. We also demonstrated that organic
substances increased the rate of cell growth under dim light and, interestingly,
C. merolae could grow heterotrophically in the presence of glycerol. Obligate
photoautotrophy should be considered an ecological, rather than physiological,
characteristic of C. merolae.
PMID- 26435906
TI - Subjective socioeconomic status and cigarette smoking interact to delay
discounting.
AB - People generally discount future outcomes, and accordingly accept immediate but
smaller gain. This research examined whether this tendency (i.e., delay
discounting) is associated with socioeconomic status (SES) and smoking status,
and hypothesized that the influence of SES on delay discounting would be
moderated by smoking status. Using an Internet survey, 206 participants made
choices between receiving hypothetical monetary rewards immediately or with a
delay of 1 year. As predicted, the rates of delay discounting were higher as
subjective socioeconomic status indicating one's relative position and standing
in a society was lower. Moreover, the tendency was clearer in smokers than in non
smokers, suggesting that cigarette smoking has a moderating effect. In contrast,
there was no effect of objective socioeconomic status representing how
individuals are able to access valued goods and services.
PMID- 26435907
TI - Primary hepatic mucosa-associated lymphoid tissue lymphoma: a case report and
literature review.
AB - Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely
rare disease. We herein describe the findings in a 74-year-old man with elevated
liver enzyme levels. Dynamic computed tomography showed focal biliary dilation
and atrophy in the posterior segment, while dynamic magnetic resonance images
revealed a small, highly enhanced small mass located at the root of posterior
branch of the biliary ducts. As the mass was not detected on abdominal
ultrasonography, a biopsy could not be performed. Cholangiocellular carcinoma was
suspected, and surgery was performed. However, the surgically resected hepatic
tumor was a nodule of aggregated lymphocytes that formed a lymphoepithelial
lesion. Immunohistochemical analysis revealed that the lymphoma cells were
positive for CD20 and CD79a, but negative for CD3. No other lymphoid lesions were
found during additional postoperative examinations. Therefore, the patient was
diagnosed with primary hepatic MALT lymphoma. He was also diagnosed with
Helicobacter pylori infection, and thus, pylorus eradication was performed. At
the time of this report, the patient was free of disease for 2 years without any
additional treatment. The present case contributed to the diagnosis and
management of this rare disease, as previously published case reports described
varying imaging features; it also suggested that preoperative diagnosis was often
difficult without biopsy.
PMID- 26435908
TI - A case of advanced rectal cancer with rectovesical and ileal fistulae that
developed hyperammonemic encephalopathy.
AB - Hyperammonemic encephalopathy is rarely caused by a urinary diversion. We herein
experienced a case of rectal carcinoma with rectovesical and ileal fistulae that
developed hyperammonemic encephalopathy. A 72-year-old man suffered from a fever,
diarrhea, pneumaturia, and fecaluria beginning in April 2013 and was referred to
our hospital in May 2013. He developed a loss of consciousness and whole body
cramping on the first hospital day. The laboratory data indicated an inflammatory
reaction and hyperammonemia with a highly elevated serum ammonia (NH3) level of
703 MUg/dl. The patient was diagnosed to have rectal carcinoma with rectovesical
and ileal fistulae according to computed tomography (CT) and a water-soluble
contrast enema. We administered a solution of branched chain amino acids (BCAA)
and antibiotics. Furthermore, we repeatedly irrigated bladder through the
urethral catheter. The patient's symptoms recovered, and the serum ammonia levels
on the second and third hospital day were decreased to 210 and 135 MUg/dl,
respectively. However, the symptoms of infection and confusion were suspected to
repeat; we elected to perform surgical treatment. An ileal disconnection with
ileocecal bypass and sigmoidostomy were effective for preventing hyperammonemic
encephalopathy.
PMID- 26435909
TI - Accessory right hepatic artery branched from gastroduodenal artery.
AB - The right hepatic artery usually branches from the common hepatic artery,
however, there are cases showing anatomic variations. We present 41-year-old
female patient with gallbladder cancer. In this case, the accessory right hepatic
artery branched from the gastroduodenal artery, passed in front of the common
bile duct and fed into the anterior segment of the liver. Cholecystectomy and
resection of the extrahepatic bile duct with hepaticoenterostomy were performed
successfully, preserving the accessory right hepatic artery. There are few
reports presenting such an extremely rare anomaly of hepatic arteries in the
English literature. Additionally, we herein present a review of the English
literature regarding anatomic variations of right hepatic artery.
PMID- 26435911
TI - Social media in clinical radiology: have you updated your status?
PMID- 26435912
TI - Why China is currently underperforming in medical innovation and what China can
do about it?-Part III: social psychology and evolutionary psychology
perspectives.
PMID- 26435910
TI - Obesity-Related Oxidative Stress: the Impact of Physical Activity and Diet
Manipulation.
AB - Obesity-related oxidative stress, the imbalance between pro-oxidants and
antioxidants (e.g., nitric oxide), has been linked to metabolic and
cardiovascular disease, including endothelial dysfunction and atherosclerosis.
Reactive oxygen species (ROS) are essential for physiological functions including
gene expression, cellular growth, infection defense, and modulating endothelial
function. However, elevated ROS and/or diminished antioxidant capacity leading to
oxidative stress can lead to dysfunction. Physical activity also results in an
acute state of oxidative stress. However, it is likely that chronic physical
activity provides a stimulus for favorable oxidative adaptations and enhanced
physiological performance and physical health, although distinct responses
between aerobic and anaerobic activities warrant further investigation. Studies
support the benefits of dietary modification as well as exercise interventions in
alleviating oxidative stress susceptibility. Since obese individuals tend to
demonstrate elevated markers of oxidative stress, the implications for this
population are significant. Therefore, in this review our aim is to discuss (i)
the role of oxidative stress and inflammation as associated with obesity-related
diseases, (ii) the potential concerns and benefits of exercise-mediated oxidative
stress, and (iii) the advantageous role of dietary modification, including acute
or chronic caloric restriction and vitamin D supplementation.
PMID- 26435913
TI - The effect of changes to MOLLI scheme on T1 mapping and extra cellular volume
calculation in healthy volunteers with 3 tesla cardiovascular magnetic resonance
imaging.
AB - BACKGROUND: Diffuse myocardial fibrosis may be quantified with magnetic resonance
(MR) by calculating extracellular volume (ECV) fraction from native and post
contrast T1 values. The ideal modified look-locker inversion recovery (MOLLI)
sequence for deriving T1 values has not been determined. This study aims to
establish if systematic differences exist between suggested MOLLI schemes.
METHODS: Twelve phantom gels were studied with inversion recovery spin echo MR at
3.0 tesla to determine reference T1. Gels were then scanned with six MOLLI
sequences (3s)3b(3s)5b; 4b(3s)3b(3s)2b; 5b(3s)3b with flip angles of both 35
degrees and 50 degrees at a range of heart rates (HRs). In 10 healthy
volunteers MOLLI studies were performed on two separate occasions. Mid
ventricular native and post contrast T1 was measured and ECV (%) calculated.
RESULTS: In phantoms, the co-efficient of variability at simulated HR [40-100]
with a flip angle of 35 degrees ranged from 6.77 to 9.55, and at 50 degrees
from 7.71 to 11.10. T1 was under-estimated by all MOLLI acquisitions. Error was
greatest with longer T1, and increased as HR increased. The 10 volunteers had
normal MR studies. Native T1 time was similar for all acquisitions but highest
with the 5b(3s)3b 35 degrees scheme (1,189.1+/-33.46 ms). Interstudy
reproducibility was similar for all MOLLIs. CONCLUSIONS: The 5b(3s)3b MOLLI
scheme agreed best with reference T1, without statistical difference between the
six schemes. The shorter breath-hold time of 5b(3s)3b scheme may be preferable in
clinical studies and warrants further investigation.
PMID- 26435914
TI - Prenatal and early postnatal lead exposure in mice: neuroimaging findings.
AB - BACKGROUND: Childhood lead exposure has been linked to adult gray matter loss
accompanied by changes in myelination and neurochemistry noninvasively revealed
by magnetic resonance imaging (MRI) methods. However, the extent, duration and
timing of lead exposure required to produce such imaging changes in humans are
difficult to ascertain. METHODS: To determine if such changes are related to
early exposure to low levels of lead, we treated mouse dams with 0, 3, or 30 ppm
of lead acetate in drinking water for 2 months prior to mating through gestation
until weaning of the offspring at post-natal day 21. Two male and two female pups
from each litter were imaged at post-natal day 60. Volumetric, diffusion tensor
imaging and magnetic resonance spectroscopy (MRS) measurements were obtained
using a seven Tesla Bruker animal MRI scanner. RESULTS: Postnatal blood lead
levels were identical between groups at the time of imaging. No effects of lead
exposure were detected in the volumetric or MRS data. Mean diffusivity in the
hippocampus showed significant effects of lead exposure and gender. CONCLUSIONS:
These data suggest that low-level, gestational lead exposure in a mouse model
produces minimal changes observed by MRI.
PMID- 26435915
TI - Application of modified reverse panoramic radiograph on lambdoid suture for age
estimation.
AB - BACKGROUND: Cranial suture closure has long been recognized as a character of
human development related to aging. For this reason, it has been utilized for
various forensic and archaeological studies to determine the age of an
unidentified/or skeletonized individuals. Various cadaveric studies have
established the role of lambdoid suture in age estimation, but not routinely
practiced. The objective is to establish if any correlation exists between
individual's age and lambdoid sutures closure status (ectocranially) in mortals
through modified reverse panoramic radiograph (RPRg). METHODS: Total number of 85
subjects, 25 years and beyond were included in the study, and divided into four
groups with an age interval of 10 years. Assessment of lambdoid suture closure
was done according to Frederic Rating Scale on modified RPRg. Data obtained was
subjected to statistical analysis using Spearman's correlation test. RESULTS: A
significant difference was observed between the age group and suture closure.
Correlation coefficient of 0.570 was obtained, and was interpreted as a good
correlation between the age and suture closure status with a P value of <0.001.
CONCLUSIONS: Lambdoid suture can be very effective and practical tool for age
assessment in mortals through modified RPRg (ectocranially).
PMID- 26435916
TI - Use of 100 kV versus 120 kV in computed tomography pulmonary angiography in the
detection of pulmonary embolism: effect on radiation dose and image quality.
AB - OBJECTIVE: To determine the effective radiation dose and image quality resulting
from 100 versus 120 kilovoltage (kV) protocols among patients referred for
computed tomography pulmonary angiography (CTPA). METHODS: Sixty-six patients
with clinical suspicion of pulmonary embolism (PE) were prospectively enrolled.
Two CTPA protocols (group A: n=33, 100 kV/115 mAs; group B: n=33, 120 kV/90 mAs)
were compared. Two experienced radiologists assessed image quality in terms of
diagnostic performance and effect of artefacts. Image quality parameters [CT
attenuation, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)] and
effective radiation dose between the two protocols were compared. RESULTS: The
contrast enhancement in central and peripheral pulmonary arteries was
significantly higher in group A than in group B (P<0.001) with the identical SNR
(P=0.26), whereas the CNR was significantly higher in group A than in group B
(P<0.001). The effective radiation dose for the 100 and 120 kV scans was 3.2 and
6.8 mSv, respectively. CONCLUSIONS: Reducing the tube voltage from 120 to 100 kV
in CTPA allows a significant reduction of radiation dose without significant loss
of diagnostic image quality.
PMID- 26435917
TI - Total gadolinium tissue deposition and skin structural findings following the
administration of structurally different gadolinium chelates in healthy and
ovariectomized female rats.
AB - OBJECTIVE: To assess the retention of gadolinium (Gd) in skin, liver, and bone
following gadodiamide or gadoteric acid administration. METHODS: Gd was measured
in skin, liver and femur bone in female rats 10 weeks after administration of
17.5 mmol Gd/kg over 5 days of Gd agents. Rat skin microscopy, energy filtering
transmission electron microscopy and elemental analysis were performed, and
repeated after receiving the same dosage of gadodiamide in rats with osteoporosis
induced with bilateral ovariectomy (OVX). The OVX was performed 60 days after the
last injection of gadodiamide and animals sacrificed 3 weeks later. RESULTS: Gd
concentration was 180-fold higher in the skin, 25-fold higher in the femur, and
30-fold higher in the liver in rats received gadodiamide than rats received
gadoteric acid. The retention of Gd in the skin with gadodiamide was associated
with an increase in dermal cellularity, and Gd encrustation of collagen fibers
and deposition inside the fibroblasts and other cells. No differences in Gd
concentration in liver, skin, and femur were observed between rats receiving
gadodiamide with or without OVX. CONCLUSIONS: Gd tissue retention with
gadodiamide was higher than gadoteric acid. Tissues Gd deposition did not alter
following gadodiamide administration to ovariectomized rats.
PMID- 26435918
TI - Decoupling and matching network for monopole antenna arrays in ultrahigh field
MRI.
AB - BACKGROUND: Radiative coil arrays, e.g., dipole or monopole arrays, are
increasingly used in MR signal excitation and reception for ultrahigh field MRI.
Technically, it is challenging to suppress the electromagnetic (EM) coupling of
radiative array elements due to their unique structures. METHODS: In this study,
we proposed a combined decoupling and matching network (DMN) for monopole arrays
for MRI applications. Compared with separate decoupling network and matching
network, the combined network proposed here needs less components and rather
suitable for decoupling radiative arrays in MRI. RESULTS: Our study shows that
the transmission coefficient between two coupled monopoles can be reduced from -5
dB to -24.8 dB by using the combined DMN. It is also clearly demonstrated in this
study that this decoupling method is a port decoupling method rather than an
element decoupling method. CONCLUSIONS: With the proposed DMN, the monopole coil
provides locally strong and spatially diverse B1 fields, which is essential to
the improvement of MR sensitivity and parallel imaging performance.
PMID- 26435919
TI - Automatic multi-parametric quantification of the proximal femur with quantitative
computed tomography.
AB - BACKGROUND: Quantitative computed tomography (QCT) imaging is the basis for
multiple assessments of bone quality in the proximal femur, including volumetric
bone mineral density (vBMD), tissue volume, estimation of bone strength using
finite element modeling (FEM), cortical bone thickness, and computational-anatomy
based morphometry assessments. METHODS: Here, we present an automatic framework
to perform a multi-parametric QCT quantification of the proximal femur. In this
framework, the proximal femur is cropped from the bilateral hip scans, segmented
using a multi-atlas based segmentation approach, and then assigned volumes of
interest through the registration of a proximal femoral template. The proximal
femur is then subjected to compartmental vBMD, compartmental tissue volume, FEM
bone strength, compartmental surface-based cortical bone thickness, compartmental
surface-based vBMD, local surface-based cortical bone thickness, and local
surface-based cortical vBMD computations. Consequently, the template
registrations together with vBMD and surface-based cortical bone parametric maps
enable computational anatomy studies. The accuracy of the segmentation was
validated against manual segmentations of 80 scans from two clinical facilities,
while the multi-parametric reproducibility was evaluated using repeat scans with
repositioning from 22 subjects obtained on CT imaging systems from two
manufacturers. RESULTS: Accuracy results yielded a mean dice similarity
coefficient of 0.976+/-0.006, and a modified Haussdorf distance of 0.219+/-0.071
mm. Reproducibility of QCT-derived parameters yielded root mean square
coefficients of variation (CVRMS) between 0.89-1.66% for compartmental vBMD; 0.20
1.82% for compartmental tissue volume; 3.51-3.59% for FEM bone strength; 1.89
2.69% for compartmental surface-based cortical bone thickness; and 1.08-2.19% for
compartmental surface-based cortical vBMD. For local surface-based assessments,
mean CVRMS were between 3.45-3.91% and 2.74-3.15% for cortical bone thickness and
vBMD, respectively. CONCLUSIONS: The automatic framework presented here enables
accurate and reproducible QCT multi-parametric analyses of the proximal femur.
Our subjects were elderly, with scans obtained across multiple clinical sites and
manufacturers, thus documenting its value for clinical trials and other multi
site studies.
PMID- 26435920
TI - Correlation of normal thyroid ultrasonography with thyroid tests.
AB - BACKGROUND: Thyroid disorders are frequently seen in the community. Thyroid
ultrasonography (US) is commonly used in the diagnosis of thyroid diseases. The
relationship between heterogeneous echogenicity of thyroid gland and thyroid
tests are well known. METHODS: The aim of this study is to evaluate the
correlation of normal US with the thyroid tests. A total of 681 individuals were
enrolled in the study. Individuals were separated into two groups as normal
(group 1) and hypoechoic (group 2) according to the echogenicity in US. Subjects
with nodular thyroid lesions were excluded from the study. Thyroid stimulating
hormone (TSH), free T4 (fT4), thyroid peroxidase antibody (TPOAb) and anti
thyroglobulin antibody (TgAb) values were recorded in both groups and thyroid
stimulating hormone receptor antibody (TRAb) was recorded in individuals with low
TSH. RESULTS: 86.1% of individuals in group 1 had normal TSH, 93.7% had normal
thyroid antibodies and in 77.6% of individuals, all thyroid tests performed were
normal. In the 6.9% of the group 2, all reviewed thyroid tests were normal
(P<0.001). CONCLUSIONS: Our study shows that US is correlated with normal thyroid
function tests and is a valuable tool in the prediction of normal thyroid
function.
PMID- 26435921
TI - Analyzing bone remodeling patterns after total hip arthroplasty using
quantitative computed tomography and patient-specific 3D computational models.
AB - BACKGROUND: Computational models in the form of finite element analysis technique
that incorporates bone remodeling theories along with DEXA scans has been
extensively used in predicting bone remodeling patterns around the implant.
However, majority of such studies used generic models. Therefore, the aim of this
study is to develop patient-specific finite element models of total hip
replacement patients using their quantitative computed tomography (QCT) scans and
accurately analyse bone remodelling patterns after total hip arthroplasty (THA).
METHODS: Patient-specific finite element models have been generated using the
patients' QCT scans from a previous clinical follow-up study. The femur was
divided into five regions in proximal-distal direction and then further divided
into four quadrants for detailed analysis of bone remodeling patterns. Two types
of analysis were performed-inter-patient and intra patient to compare them and
then the resulting bone remodeling patterns were quantitatively analyzed.
RESULTS: Our results show that cortical bone density decrease is higher in
diaphyseal region over time and the cancellous bone density decreases
significantly in metaphyseal region over time. In metaphyseal region, posterior
medial (P-M) quadrant showed high bone loss while diaphyseal regions show high
bone loss in anterior-lateral (A-L) quadrant. CONCLUSIONS: Our study demonstrated
that combining QCT with 3D patient-specific models has the ability of monitoring
bone density change patterns after THA in much finer details. Future studies
include using these findings for the development of a bone remodelling algorithm
capable of predicting surgical outcomes for THA patients.
PMID- 26435922
TI - Errors in quantitative T1rho imaging and the correction methods.
AB - The spin-lattice relaxation time constant in rotating frame (T1rho) is useful for
assessment of the properties of macromolecular environment inside tissue.
Quantification of T1rho is found promising in various clinical applications.
However, T1rho imaging is prone to image artifacts and quantification errors,
which remains one of the greatest challenges to adopt this technique in routine
clinical practice. The conventional continuous wave spin-lock is susceptible to
B1 radiofrequency (RF) and B0 field inhomogeneity, which appears as banding
artifacts in acquired images. A number of methods have been reported to modify
T1rho prep RF pulse cluster to mitigate this effect. Adiabatic RF pulse can also
be used for spin-lock with insensitivity to both B1 RF and B0 field
inhomogeneity. Another source of quantification error in T1rho imaging is signal
evolution during imaging data acquisition. Care is needed to affirm such error
does not take place when specific pulse sequence is used for imaging data
acquisition. Another source of T1rho quantification error is insufficient signal
to-noise ratio (SNR), which is common among various quantitative imaging
approaches. Measurement of T1rho within an ROI can mitigate this issue, but at
the cost of reduced resolution. Noise-corrected methods are reported to address
this issue in pixel-wise quantification. For certain tissue type, T1rho
quantification can be confounded by magic angle effect and the presence of
multiple tissue components. Review of these confounding factors from inherent
tissue properties is not included in this article.
PMID- 26435923
TI - Identifying osteoporotic vertebral fracture.
AB - Osteoporosis per se is not a harmful disease. It is the sequela of osteoporosis
and most particularly the occurrence of osteoporotic fracture that makes
osteoporosis a serious medical condition. All of the preventative measures,
investigations, treatment and research into osteoporosis have one primary goal
and that is to prevent the occurrence of osteoporotic fracture. Vertebral
fracture is by far and away the most prevalent osteoporotic fracture. The
significance and diagnosis of vertebral fracture are discussed in this article.
PMID- 26435924
TI - State-of-the-art in retinal optical coherence tomography image analysis.
AB - Optical coherence tomography (OCT) is an emerging imaging modality that has been
widely used in the field of biomedical imaging. In the recent past, it has found
uses as a diagnostic tool in dermatology, cardiology, and ophthalmology. In this
paper we focus on its applications in the field of ophthalmology and retinal
imaging. OCT is able to non-invasively produce cross-sectional volumetric images
of the tissues which can be used for analysis of tissue structure and properties.
Due to the underlying physics, OCT images suffer from a granular pattern, called
speckle noise, which restricts the process of interpretation. This requires
specialized noise reduction techniques to eliminate the noise while preserving
image details. Another major step in OCT image analysis involves the use of
segmentation techniques for distinguishing between different structures,
especially in retinal OCT volumes. The outcome of this step is usually thickness
maps of different retinal layers which are very useful in study of
normal/diseased subjects. Lastly, movements of the tissue under imaging as well
as the progression of disease in the tissue affect the quality and the proper
interpretation of the acquired images which require the use of different image
registration techniques. This paper reviews various techniques that are currently
used to process raw image data into a form that can be clearly interpreted by
clinicians.
PMID- 26435925
TI - Bedside ultrasonography for diagnosis of pneumothorax.
AB - Ultrasonography (US) has found its way into the critical care and emergency
settings for the evaluation of acute respiratory failure conditions in recent
years. It is useful for the diagnosis of varieties of abnormalities involving
pleura and lung such as pleural effusion, alveolar interstitial syndrome, and
pneumothorax (PTX). In addition to its reproducibility and timeliness, US has
high sensitivity and specificity for the diagnosis of these conditions. The most
widely used method for bedside evaluation of PTX is chest X-ray (CXR). However,
the diagnostic sensitivity of CXR in detecting PTX is limited especially in
occult PTX and when the patient is assumed supine position. Computed tomography
(CT) is the gold standard in the evaluation of PTX, but is limited by its high
radiation exposure and safety concerns in transporting critically ill patients.
In this paper we review current advances in PTX diagnosis using US.
PMID- 26435926
TI - Tracheal septum: real or virtual?
AB - Tracheal septum has never been reported in human beings, though it's a common
occurrence in few lower vertebrates. We are presenting a case of thick tracheal
secretion that appeared as a midline tracheal septum and prompted the clinician
to go for bronchoscopy.
PMID- 26435927
TI - Changes in the skeletal system and extramedullary hematopoiesis in a patient with
thalassemia.
PMID- 26435928
TI - Fahr disease: use of susceptibility-weighted imaging for diagnostic dilemma with
magnetic resonance imaging.
AB - Fahr disease (FD) is a well-defined rare neurodegenerative disease that is
characterized by idiopathic bilateral symmetric extensive striopallidodentate
calcifications. The patients may present with diverse manifestations, most
commonly movement disorder, cognitive impairment, and ataxia. Computed tomography
(CT) is considered to be critical for accurate diagnosis because it is difficult
to reliably identify calcifications by routine magnetic resonance imaging (MRI).
Susceptibility-weighted imaging (SWI) is a relatively new 3D gradient-echo (GE)
MR sequence with special phase and magnitude processing. SWI phase images can
recognize calcifications definitively with higher sensitivity compared to other
MRI sequences. In this article, we present two cases of FD with different
manifestations and neuroimaging in different age groups and genders, which were
diagnosed by SWI and confirmed with CT, and we discuss the contribution of SWI in
the diagnosis of FD. In conclusion, we suggest integrating SWI with MRI protocol
to identify calcifications in suspicion of neurodegenerative disorders.
PMID- 26435929
TI - Flow void artifact mimicking aneurysm in the anterior communicating artery region
on T1- and T2-weighted images.
PMID- 26435930
TI - Four dimensional magnetic resonance velocimetry for complex flow in the jugular
vein.
PMID- 26435931
TI - Three-dimensional speckle-tracking echocardiography for spatial evaluation of
pulmonary vein (from the MAGYAR-Path Study).
PMID- 26435932
TI - Anatomical Variations of Upper Segmental Renal Artery and Clinical Significance.
AB - INTRODUCTION: Classically each kidney is supplied by a single renal artery. In
its course renal artery divides into anterior and posterior division, both of
these division further divide into segmental arteries that are apical, upper,
middle, lower and posterior. Segmental arteries are representing an end artery
and they form independent renal segments. In their course they are closely
related with collecting system. So, a thorough in depth knowledge of the
variations in segmental arteries is a basic requirement for surgeons. AIM: To
observe and investigate the anatomical variations in arterial pattern of upper
segmental renal artery and its relations with collecting system of ducts in human
kidneys. MATERIALS AND METHODS: Fifty human kidneys of both sexes were observed
and studied by corrosion cast method. Different colour coded cast material (butyl
butyrate) like red for artery and black for collecting ducts were used. 20%
solution of butyl butyrate in acetone was injected into renal artery and ureter
of the kidneys. After polymerization (24 hours) these kidneys were kept immersed
in a bath of concentrated KOH solution at 50(0)C for 24-48 hours for corrosion to
obtain the endocasts. These endocasts were cleaned and washed under running tap
water and photographed. RESULTS: In present study upper segmental artery was
found in 49 (98%) kidneys. It was absent in 1 (2%) kidney. We observed four types
of variations in arterial pattern of upper segmental artery namely Upper
Segmental Artery Type-1 (USAT1), Upper Segmental Artery Type-2 (USAT2), Upper
Segmental Artery Type-3 (USAT3), Upper Segmental Artery Type-4 (USAT4) and they
were found in 20 (40%), 14 (28%), 10 (20%), 5 (10%) kidneys respectively. We also
observed two different variations in the anatomical relations between upper
segmental artery and collecting system namely Upper Segmental Artery Group -1
(USAG1) and Upper Segmental Artery Group-2 (USAG2). USAG1 was found in 40 (80%)
kidneys and USAG2 in 9 (18%) kidneys respectively. CONCLUSION: Anatomical
knowledge of these variations is very important and useful for the uro-surgeons
for best outcome and minimal complications in and during nephrectomies, removal
of calculi, surgery of renal tumors or other various intrarenal surgeries.
PMID- 26435933
TI - Morphology of Sigmoid Colon in South Indian Population: A Cadaveric Study.
AB - INTRODUCTION: Sigmoid volvulus is a common etiological factor in acute large
bowel obstruction. The increased length of sigmoid colon is attributed as one of
the causes of sigmoid volvulus. AIM: The aim of this study was to find the
morphology of sigmoid colon in South Indian population using cadavers. MATERIALS
AND METHODS: The present study was performed with 31 cadavers used for teaching
purpose. The sigmoid colon was classified into classical, long-narrow and long-
broad types by their disposition in the abdominal cavity. The sigmoid loop's
relation to pelvic brim was also observed and grouped as pelvic and suprapelvic
in position. The length of sigmoid colon along the mesenteric and antimesenteric
border, height and width of sigmoid mesocolon in relation to the pelvic brim and
the root of mesentery were measured in the study. RESULTS: The study showed that
the majority of the sigmoid colons fell into the classical type (47.6%). The
sigmoid colon in pelvic position was significantly more prevalent. The mean
length of sigmoid colon was 15.2 +/- 4.4cm and 19.2 +/- 6cm considering the
pelvic brim and root of mesentery as reference points of measurement
respectively. The mean length along antimesenteric border was 22.3 +/- 7.9cm and
25 +/- 8.7cm along the same reference points. The mean length of mesocolon height
was 6.5 +/- 3cm with reference to pelvic brim and 7.3 +/- 3cm with reference to
root of Sigmoid mesocolon respectively. The mean width of mesocolon was 7.4 +/-
3cm (pelvic brim) and 8 +/- 2cm (root of Sigmoid mesocolon) There was a positive
correlation of sigmoid colon length with the height of the mesocolon. The gender
analysis showed that males had statistically significant longer sigmoid colon and
mesocolon. CONCLUSION: This study documents that the South Indian population has
a more classical type of sigmoid colon and that the anatomical dimensions of
sigmoid colon and its mesocolon is significantly longer in males.
PMID- 26435934
TI - A Morphometric Study of the Patterns and Variations of the Acromion and Glenoid
Cavity of the Scapulae in Egyptian Population.
AB - BACKGROUND: Owing to its many variations, scapula became one of the most
interesting bones of the human skeleton. AIM: To measure acromial and glenoid
morphology in to describe their anatomical patterns and variations in Egyptians
to establish possible morphofunctional correlations related to race, geographic
region and literature data. MATERIALS AND METHODS: One hundred and sixty scapulae
of unknown age and sex were studied. Morphological shapes of the tip of the
acromion; types of acromion; and morphological shapes of the glenoid were
evaluated. Length and width of the scapulae, length, breadth and thickness of the
acromion process and distances of the acromio-coracoid and acromio-glenoid in
addition to glenoid diameters were measured. STATISTICAL ANALYSIS: The
morphometric values of the two sides were analysed using an unpaired t-test.
Statistical significance was set p<= 0.05. RESULTS: The intermediate shape of the
acromion presented with the highest incidence, while the cobra shaped presented
with the lowest distribution in both sides. The oval shaped glenoid cavity
presented with the highest incidence while the inverted coma shaped showed the
lowest incidence. These results are in match with other population. However, the
morphometric values of the scapula, acromion process and glenoid cavity were
higher than reported in Turkish and Indians. CONCLUSION: Our data are important
to compare Egyptian scapulae to those from various other races that could
contribute to demographic studies of shoulder disease probability and management
in Egyptian population.
PMID- 26435935
TI - A Study of Variations in the Origin of Obturator Artery and its Clinical
Significance.
AB - INTRODUCTION: The large number of organs and anatomical structures within the
cramped pelvic cavity makes the study of vascular pattern and their variations of
much importance in this particular anatomical region. Clear awareness of the
vascular anatomy of pelvis is critical in surgeries performed here, which require
ligation of the arteries concerned and also because such anomalous origins may
cause profuse bleeding during surgical procedures. This is particularly true with
regard to the variations in the origin of the obturator artery, while performing
pelvic and groin surgeries. AIM: The aim of the present study was to find out the
prevalence of normal and aberrant origins of obturator artery and to describe its
surgical implications. MATERIALS AND METHODS: The study was carried out on fifty
hemipelvises of embalmed cadavers and the origin and course of the arteries were
traced and noted. RESULTS: Of the 50 pelvic halves, in 27 specimens, the
obturator took origin from the anterior division of internal iliac artery.
Remaining 23 specimens showed variations. The origin of the obturator artery was
from the inferior epigastric artery in 11 cases, from the common stem of the
internal iliac artery and the external iliac artery in 2 cases each, from the
posterior trunk of the internal iliac artery in 5 and one each from superior
gluteal, inferior gluteal, and internal pudendal artery. CONCLUSION: The present
study indicates that the origin of the obturator artery is highly variable. It
can take origin from the stem of the internal iliac artery or from its anterior
or posterior division, or from one of the branches of the divisions. It can also
take origin from external iliac artery or its inferior epigastric branch.
Advancements in diagnostic and surgical techniques in obstetric procedures and
urogenital interventions make it essential to have a clear-cut understanding of
the vasculature in the abdomen and pelvis.
PMID- 26435936
TI - Anatomical Description and Clinical Relevance of a Rare Variation in the
Mesenteric Arterial Arcade Pattern.
AB - Solitary vascular variations of the mesenteric arteries are extremely rare and
have been seldom reported in the past. The aim of this study is to emphasize the
anatomical and clinical relevance of one such rare variation of inferior
mesenteric artery (IMA). The current case anomaly was incidentally observed while
guiding the undergraduate medical students in the dissection of the mesenteric
region of the abdomen in an Indian cadaver. An Accessory left colic artery was
seen to be branching off from the Inferior Mesenteric artery and further dividing
into two transverse branches which took part in the formation of arterial arc for
the perfusion of the transverse and the descending colon. Awareness of such
aberrant branches of Inferior Mesenteric artery helps in optimal selection of the
mode of treatment or operative planning. Additionally, this knowledge minimizes
possible iatrogenic injuries resulting from surgeries. Moreover, surgical anatomy
of anomalous branches of Inferior Mesenteric artery is extremely essential for
planning and successfully executing reconstructive procedures using these
branches as pedicles for the transposed part of the colon.
PMID- 26435937
TI - Congenital Fusion of C6 and C7 Vertebra-A Case Report.
PMID- 26435938
TI - Comparative Analysis of Urinary Total Proteins by Bicinchoninic Acid and
Pyrogallol Red Molybdate Methods.
AB - BACKGROUND: The concentration of total proteins in urine is a good index of renal
function, but its determination is found to be unreliable. The pyrogallol red
molybdate (PRM) method for urine total proteins is being widely used in most of
the hospitals because of its high sensitivity, better precision and its
practicability. Bicinchoninic acid method (BCA) is also used for protein
estimation and there have been no studies comparing this method with the PRM
method in human urine samples. BCA method overestimates the urinary protein
concentration in the presence of interfering substances. After removing the
interfering substances present in the human urine samples the results of BCA
method were compared with the PRM method. AIM: The purpose of the study is to
identify whether the results of urine total proteins by BCA method are comparable
to PRM method and can be used as an alternative to the PRM method. SETTING AND
DESIGN: This is a cross-sectional study done on fresh urine specimens from the
hospital laboratory, covering a wide range of protein concentrations. MATERIAL
AND METHODS: Fresh urine specimens covering a wide range of protein
concentrations (urine dipstick: nil, trace, 1+, 2+ and >= 3+) of 36 patients were
analysed by both the methods. STATISTICAL ANALYSIS: Imprecision was determined by
repeated analysis study and Inaccuracy was assessed by comparing the results of
the patient's urine samples by both the methods using correlation plots, Bland
and Altman, and Passing and Bablok regression analyses. RESULTS: The coefficient
of variation and mean (SD) for the BCA method were 4.6% and 799.1 (882.5) mg/L
and for the PRM method were 5.1% and 802.1 (911.9) mg/L. The Pearson correlation
coefficient, r was 0.93 (p < 0.0001). Method agreement studies showed no
significant constant and proportional bias between both the methods. CONCLUSION:
In urine which is subjected to removal of interfering substances, the BCA results
are comparable to PRM method.
PMID- 26435939
TI - Comparing Utility of Anthropometric Indices Based on Gender Differences in
Predicting Dyslipidaemia in Healthy Adults.
AB - INTRODUCTION: Anthropometry is a simple reliable method for quantifying body
proportions by measuring body length, weight and circumferences. AIM: Our
intention in this study was to compare sensitivities and positive predictive
values of waist circumference (WC), waist-hip ratio (WHR), waist-height ratio
(WHtR) and body mass index (BMI) in identifying healthy subjects, males and
females separately for identifying obesity associated dyslipidemia. MATERIALS AND
METHODS: We analysed randomly selected 100 healthy subjects (males:58%,
females:42%) between 25 and 60 years of age attending tertiary health care center
in South India, after obtaining informed consent and Institutional Ethical
Clearance. WC, WHR, WHtR and BMI of all the enrolled subjects were measured and
estimated. Their fasting serum lipid profile was assessed. Subjects were divided
based on their gender and each group was then categorized as obese and non-obese
using anthropometric parameters and their individual serum lipid profile values
depending on the cut off standards as per WHO and ATP III guidelines and
compared. Data obtained was statistically analysed. RESULTS: Mean values of WC,
WHR, WHtR and BMI were highly significant (p<0.000) in obese in both males (97.43
+/- 6.21cm, 0.96 +/- 0.04, 0.61 +/- 0.05, 27.72 +/- 2.45kg/m(2)) and females
(91.82 +/- 5.18cm, 0.92 +/- 0.06, 0.60 +/- 0.04, 27.70 +/- 3.44kg/m(2)) when
considered separately compared to non-obese males (82.27 +/- 5.33cm, 0.83 +/-
0.033, 0.51 +/- 0.03, 22.80 +/- 2.11kg/m(2)) and females (71.68 +/- 7.33cm, 0.78
+/- 0.03, 0.48 +/- 0.03, 21.82 +/- 1.98kg/m(2) respectively). WC was more
sensitive for predicting the altered lipid profile (85%) in females and WHR (65%)
in males. WHR showed higher ability to correctly predict the occurrence of
dyslipidemia in the obese males (90% positive predictive value) and WHtR in
females (92%). CONCLUSION: The present study inferred that WC, WHR are more
sensitive while WHR and WHtR have a higher positive predictive value than BMI in
identifying dyslipidemia in healthy males and females.
PMID- 26435940
TI - Analysis of Antibiotic Resistance Genes and its Associated SCCmec Types among
Nasal Carriage of Methicillin Resistant Coagulase Negative Staphylococci from
Community Settings, Chennai, Southern India.
AB - OBJECTIVE: The study was designed to find the distribution of SCCmec types and
the various antibiotic resistance genes amongst MR-CoNS isolates from
asymptomatic individuals. MATERIALS AND METHODS: A total of 145 nasal swabs were
collected from asymptomatic healthy individuals from community settings.
Identification and speciation of CoNS were done by standard biochemical methods.
Screening of methicillin resistance (mecA gene) and detection of various
antibiotic resistant genes were done using multiplex PCR method. SCCmec types (I
V) were determined using multiplex PCR. RESULTS: 50 (44.6%) isolates were found
to be methicillin resistant both by cefoxitin method and multiplex PCR. S.
epidermidis (40%) was the predominant species followed by S. haemolyticus (28%),
S. hominis (20%) and S. warneri (12%). Highest resistance was shown for
cotrimoxazole (26%), followed by ciprofloxacin (24%), tetracycline (20%),
erythromycin (18%), fusidic acid (10%) and mupirocin (6%). Among SCCmec types, 44
isolates showed single type, including type I (30%), type IV (24%), type II
(18%), type V (14%) and type III (2%). 6 isolates showed two types, III+IV (n=
2), II+V (n=2), IV+V (n=1) and type I+V (n=1). CONCLUSION: In conclusion, to the
best of our knowledge, this is the first study in India to study the distribution
of antibiotic resistant genes and SCCmec types among MR-CoNS from community
settings. This study highlights high prevalence of MR-CoNS in community and its
role in harbouring genetically diverse SCCmec elements as antibiotic resistance
determinant.
PMID- 26435941
TI - Evaluation of LAMP Assay Using Phenotypic Tests and Conventional PCR for
Detection of nuc and mecA genes Among Clinical Isolates of Staphylococcus spp.
AB - INTRODUCTION: The purpose of this study is to develop a nuc and mecA gene
specific Loop-mediated isothermal Amplification (LAMP) assay for rapid
identification and detection of methicillin resistant Staphylococcus aureus among
clinical isolates. MATERIALS AND METHODS: A total of 100 (70 from pus and 30 from
blood), clinical isolates of Staphylococcus spp were screened for the nuc gene to
differentiate between S.aureus and Coagulase negative Staphylococci (CONS) by a
nuc gene specific LAMP assay. The isolates were also screened for the presence of
the mec Agene by the mecA specific LAMP assay. The results were compared with the
phenotypic identification and methicillin resistance by Vitek-2 system
(bioMerieux, Marcy l'Etoile, France) and conventional PCR. RESULTS: Among 100
Staphylococcus isolates, there were 82 (82%) Staphylococcus aureus isolates and
18 (18%) coagulase negative Staphylococcus as detected by the Vitek 2,
conventional PCR and the LAMP assay using the nuc gene. The mecA gene was
detected by the LAMP assay in 56(56%) isolates (44 Methicillin resistant
Staphylococcus aureus (MRSA) and 12 Methicillin resistant coagulase negative
Staphylococcus (MRCONS), which were also identified by the Vitek 2 and
conventional PCR as methicillin resistant. The results of the LAMP assay were
available within 90min as compared to the Vitek 2 results (18- 24hours) and
conventional PCR (3-4 hours). CONCLUSION: The present study proved that LAMP
assay can be used for the simultaneous differentiation of Staphylococcal spp and
detection of methicillin resistance.
PMID- 26435942
TI - Aerobic Bacteriological Study of Acute Exacerbations of Chronic Obstructive
Pulmonary Disease.
AB - BACKGROUND: The natural history of chronic obstructive pulmonary disease is
characterized by frequent exacerbations. Majority of exacerbations are infectious
and bacteria responsible for 30-50% of these cases. The purpose of this study was
to determine the bacteriology of acute exacerbations of chronic obstructive
pulmonary disease in hospitalized patients in our institution and their
antibiotic susceptibility pattern to formulate cost effective antibiotic strategy
and reducing the emergence of drug resistance. MATERIALS AND METHODS: One hundred
and seven clinically diagnosed cases of acute exacerbations of chronic
obstructive pulmonary disease admitted in medicine, tuberculosis and chest wards
were selected for the study. Direct gram stain was done for all sputum samples.
The suitable sputum samples were cultured. Identification of organism and
antimicrobial susceptibility testing was done by standard microbiological
techniques. RESULTS: Our study showed growth of pathogenic organisms in 41.12%
cases. Males (67.29%) are more affected than females (32.71%). Gram negative
bacilli were more isolated than gram positive cocci. The commonest isolate was
Klebsiella pneumoniae 15 (38.46%), followed by Staphylococcus aureus 9 (23.08%),
Streptococcus species 6 (15.39%), Pseudomonas aeruginosa 4 (10.26%), E.coli 2
(5.13%), Acinetobacter species 2 (5.13%) and Enterobacter species 1(2.56%). The
antibiotic susceptibility reveals that vancomycin, linezolid, azithromycin and
clarithromycin were most effective drugs for gram positive cocci, meropenem &
piperacillin-tazobactam for gram negative bacilli and amikacin & levofloxacin for
both gram positive cocci & gram negative bacilli. CONCLUSION: In developing
country like India acute exacerbations of chronic obstructive pulmonary disease
is common in adults more than 50 years of age due to smoking habits and high
indoor pollution. This leads to a major impact on the quality of life of patients
with the condition. They are a major cause of hospital admission and health care
utilization.
PMID- 26435943
TI - Invitro Antibacterial Activity of the Prosopis Juliflora Seed Pods on Some Common
Pathogens.
AB - INTRODUCTION: Prosopis juliflora is probably the most widespread species of genus
Prosopis and it is a good source of compounds that have been shown to be
pharmacologically active. This plant has been used as a traditional treatment for
several diseases. AIM: To investigate the in-vitro antibacterial activity of the
P. juliflora seed pods from Bushehr, South West of Iran. MATERIALS AND METHODS:
In the present study, the antibacterial activity of P. juliflora seed pods
extract was tested against Staphylococcus aureus, Staphylococcus epidermidis,
Escherichia coli and Pseudomonas aeruginosa. The minimum inhibitory concentration
(MIC) of the extract was determined for each test microorganism. RESULTS: P.
juliflora seed pods extract exhibited antibacterial activity against all four
test organisms. The MIC of the extract was 0.312 mg/ml and 0.078 mg/ml for S.
aureus and S. epidermidis, respectively and 1.25 mg/ml for both E.coli and
P.aeruginosa. CONCLUSION: P. juliflora seed pods from Bushehr, South West of Iran
could be an appropriate source of antibacterial compounds that makes it a
promising candidate for further studies.
PMID- 26435944
TI - Evaluation of Ica Gene in Comparison with Phenotypic Methods for Detection of
Biofilm Production by Coagulase Negative Staphylococci in a Tertiary Care
Hospital.
AB - BACKGROUND: Biofilm producing bacteria are responsible for several chronic
infections and are difficult to treat as they show much greater resistance to
antibiotics. The major virulence factor determining the pathogenicity of CoNS has
now well defined and found to be biofilm production. OBJECTIVE: The study was
conducted to isolate and characterize Coagulase Negative Staphylococci (CoNS) and
their ability to form biofilms was evaluated by phenotypic and genotypic methods.
MATERIALS AND METHODS: A total of 96 clinical isolates of CoNS were characterized
and subjected to biofilm detection by tissue culture plate method (TCP), tube
method (TM), congo red agar method (CRA) and PCR. RESULTS: Staphylococcus
epidermidis was the most commonly isolated species 76(79.17%). The ica gene was
present in 35 (36.45%) of CoNS isolates which were detected as biofilm producers
by TCP. Biofilm producing isolates showed higher antibiotic resistance(72.1%).
Majority of biofilm producers had strong association with medical device related
infections. CONCLUSION: To compare PCR based dectection method for presence of
ica genes with TCP, the test share the specific identification rates. The
sensitivity and specificity of TCP method in detection of biofilm was high in
comparison with TM and CRA. TCP can be recommended as a general screening test
for biofilm detection.
PMID- 26435945
TI - Inducible Clindamycin Resistance among Clinical Isolates of Staphylococcus aureus
from Sub Himalayan Region of India.
AB - INTRODUCTION: Clindamycin is an alternative antibiotic in the treatment of
Staphylococcus aureus (S.aureus) infections, both in infections by methicillin
susceptible and resistant (MSSA and MRSA) strains. The major problem of use of
clindamycin for staphylococcal infections is the presence of inducible
clindamycin resistance that can lead to treatment failure in such infections.
AIM: To determine inducible and constitutive clindamycin resistance among
clinical isolates of S. aureus in a tertiary care centre of sub Himalayan region
of India. MATERIALS AND METHODS: A total of 350 isolates of S. aureus from
various clinical samples were subjected to routine antibiotic sensitivity testing
by Kirby Bauer disc diffusion method. Methicillin resistance was detected by
cefoxitin (30MUg) disc. All isolates were subjected to inducible clindamycin
resistance was by Clinical Laboratory Standards Institute (CLSI) recommended D
test. RESULTS: Among 350 S.aureus isolates, 82 (23.42%) were MRSA and 268
(76.57%) were MSSA. Erythromycin resistance was detected in 137 (39.14%)
isolates. Erythromycin resistance in MRSA and MSSA was 71.6% and 29.36%
respectively. Overall clindamycin resistance was seen in 108 (30.85%) isolates.
Constitutive MSLB phenotype predominated (29.62% MRSA; 13.38% MSSA) followed by
iMLSB (28.39% MRSA; 9.29% MSSA) and MS phenotypes (13.58% MRSA; 6.69%MSSA). Both
inducible and constitutive clindamycin resistance was significantly higher
(p=0.00001, 0.0008 respectively) in methicillin resistant strains than in
methicillin susceptible strains. CONCLUSION: The present study gives a magnitude
of clindamycin resistance among clinical isolates of S. aureus from this region
of the country. Our study recommends routine testing of inducible clindamycin
resistance at individual settings to guide optimum therapy and to avoid treatment
failure.
PMID- 26435946
TI - Optical Whole-Genome Restriction Mapping as a Tool for Rapidly Distinguishing and
Identifying Bacterial Contaminants in Clinical Samples.
AB - INTRODUCTION: Optical restriction genome mapping is a technology in which a
genome is linearized on a surface and digested with specific restriction enzymes,
giving an arrangement of the genome with gaps whose order and size are unique for
a given organism. Current applications of this technology include assisting with
the correct scaffolding and ordering of genomes in conjunction with whole-genome
sequencing, observation of genetic drift and evolution using comparative genomics
and epidemiological monitoring of the spread of infections. Here, we investigated
the suitability of genome mapping for use in clinical labs as a potential
diagnostic tool. MATERIALS AND METHODS: Using whole genome mapping, we
investigated the basic performance of the technology for identifying two bacteria
of interest for food-safety (Lactobacilli spp. and Enterohemorrhagic Escherichia
coli). We further evaluated the performance for identifying multiple organisms
from both simple and complex mixtures. RESULTS: We were able to successfully
generate optical restriction maps of four Lactobacillus species as well as a
strain of Enterohemorrhagic Escherichia coli from within a mixed solution, each
distinguished using a common compatible restriction enzyme. Finally, we
demonstrated that optical restriction maps were successfully obtained and the
correct organism identified within a clinical matrix. CONCLUSION: With additional
development, whole genome mapping may be a useful clinical tool for rapid invitro
diagnostics.
PMID- 26435947
TI - Amphotericin B Resistant Apophysomyces elegans Causing Rhino-oculo-Cerebral
Mucormycosis in an Immunocompetent Host.
AB - Mucormycosis, an angioinvasive infection is caused by the ubiquitous filamentous
fungi of the order Mucorales and class Mucormycetes. Reports of this disease are
on the rise over the past few decades. Rhino-oculo-Cerebral presentation
associated with uncontrolled diabetes is the predominant characteristic of this
entity. We report here a case of rhinooculocerebral mucormycosis (ROCM) due to
Apophysomyces elegans (A. elegans) in a 45-year-old diabetic lady with background
illness of hypothyroidism and polyradiculoneuropathy. Though this condition is
usually managed with surgical debridement of the affected tissue and medical
therapy with Amphotericin B, the isolate recovered in our case was found to be
resistant to Amphotericin B.
PMID- 26435948
TI - A Case of Lower Respiratory Tract Infection with Canine-associated Pasteurella
canis in a Patient with Chronic Obstructive Pulmonary Disease.
AB - This is the report of lower respiratory tract infection with Pasteurella canis in
a chronic obstructive pulmonary disease (COPD) patient with history of casual
exposure to cats. Pasteurella species are part of the oral and gastrointestinal
flora in the canine animals. These organisms are usually implicated in wound
infection following animal bites, but can also be associated with a variety of
infections including respiratory tract infections.
PMID- 26435949
TI - Clinico-Microbiological Investigation of Catheter Associated Urinary Tract
Infection by Enterococcus faecalis: vanA Genotype.
AB - Prolonged hospitalization and exposure to third generation cephalosporins are
reported to facilitate the acquisition and colonization of Vancomycin Resistant
Enterococci (VRE). Though VRE is not uncommon in India, urinary tract infection
with a vanA genotype is a cause of serious concern as VRE co-exhibit resistance
to aminoglycosides. In India, majority of the VRE isolates recovered from
hospitalized patients include Enterococcus faecium. We report a case of catheter
associated urinary tract infection by an endogenous, multidrug resistant E.
faecalis of vanA genotype following prolonged hospitalization, ICU stay,
catheterisation and exposure to 3G cephalosporin and metronidazole. The patient
responded to linezolid therapy.
PMID- 26435950
TI - A Comparative Study of Histopathology of Astrocytomas with Intraoperative
Cytology with Special Reference to MIB-1 Labelling Index.
AB - BACKGROUND: Although radiological imaging and surgical techniques have
substantially improved, assessment of prognosis by grading astrocytoma has been
challenging task for pathologists. We have tried to assess these tumours
intraoperatively for rapid diagnosis. Also MIB-1Labelling index (MIB-1 LI) was
done to study their proliferative activity. AIMS: To compare and grade squash
smear technique with histopathology to study its utility in diagnosis of
astrocytomas. Further, to study correlation of various grades with their MIB-1
labelling index. SETTING AND DESIGNS: This study was carried out in the
Department of Pathology, SMS Medical College, Jaipur over a period of one year.
MATERIALS AND METHODS: Forty five cases of radiologically suspected astrocytomas
were submitted for intraoperative cytology and later for histopathology. Two
techniques were compared for ability to diagnose as well as grade the tumour.
Also, MIB-1 LI were performed in biopsy tissue. Histopathological and
immunological grades were compared. RESULTS: Out of 45 cases 44(97.7%) correctly
diagnosed by squash smear technique. Further significant differences seen in
values of MIB-1 LI of high-grade and low-grade astrocytomas. A progressive
increase in the MIB-1 LI was observed with increasing grades. In grade I
astrocytoma MIB-1 LI was <0.05%. In grade II astrocytoma it varied from 0.8-2.6%
except in one case where it was 3.2% who presented with a recurrent mass. In
grade III, MIB-1 LI was 3.5% to 7.5%. In grade IV was 10-20%. CONCLUSION:
Intraoperative cytology is fairly accurate and useful in intraoperative
consultation. Also, MIB-1 LI can be a useful adjunct for grading particularly in
small biopsies.
PMID- 26435951
TI - Analysis of Human Papilloma Virus 16/18 DNA and its Correlation with p16
Expression in Oral Cavity Squamous Cell Carcinoma in North-Eastern India: A
Chromogenic in-situ Hybridization Based Study.
AB - BACKGROUND: The incidence of head and neck squamous cell carcinoma (HNSCC) is
quite high in North Eastern India. Apart from the traditional risk factors like
tobacco and alcohol consumption, human papilloma virus (HPV) is now considered an
established causative agent. These HPV related tumour have a clinico-pathological
profile that is quite divergent from conventional non-HPV related tumours.
Association of HPV in oral cancers has not been explored in north-east India.
MATERIALS AND METHODS: Thirty-one patients with oral cavity squamous cell
carcinoma (OSCC) on treatment from October 2010 to January 2013 were included in
the study. Patients who received neo-adjuvant chemotherapy were excluded. HPV
16/18 DNA was evaluated using Chromogenic in-situ Hybridization (CISH). Presence
of nuclear signals was taken as positive HPV expression. p16 was evaluated using
immunohistochemistry and was considered positive if >= 80% of the tumour cells
showed strong and diffuse nuclear/cytoplasmic immunostaining. The results were
analysed using Fisher exact test and confidence interval was calculated where
required. RESULTS: The study group age ranged from 30 to 80 years (median age-
54.2 years). The most common site was gum, with well differentiated squamous cell
carcinoma being the most common histology. HPV 16/18 DNA was positive in 29% (95%
CI: 13.03% - 44.97%) cases and had a clear tendency towards statistical
significance with non-smoker cases (p=0.05), lymph node metastasis (p=0.05) and a
significant correlation with p16 overexpression (p=0.04). There was no
significant correlation with other clinico-pathological parameters. CONCLUSION:
HPV 16/18 is associated with OSCC, commonly seen among non-smokers and may be
related to nodal metastasis. So, HPV may be used as a prognostic factor in OSCC
and p16 may be considered as a surrogate marker for HPV.
PMID- 26435952
TI - Enteric Duplication Cysts in Children: A Clinicopathological Dilemma.
AB - AIM: Enteric duplication cysts are rare and uncommon congenital malformations
formed during the embryonic period of the development of human digestive system
and are mainly encountered during infancy or early childhood, but seldom in
adults. The clinical presentation is extremely variable depending upon its size,
location and type. We present six cases of enteric duplication cysts with diverse
clinico-pathological features. MATERIALS AND METHODS: This study was carried out
in the Department of Pathology and Department of Paediatric Surgery, Vardhman
Mahavir Medical College and Safdarjung Hospital, New Delhi, India for a period of
2 years (January 2013 - December 2014). We retrospectively analyzed six patients
of enteric duplication cysts based on data obtained, which consisted of patient's
age, sex, clinical presentation, radiological features, operative findings and
histopathology report. The data collected was analyzed by descriptive statistics.
RESULTS: Six children between age range of 3 days to 10 years had enteric
duplication cysts. Two had ileal and one each were of pyloroduodenal, colonic and
rectal duplication cyst. In one patient a presumptive diagnosis of enteric
duplication cyst was made. Radiology played an important contributory role in
diagnosis of these cysts in all the patients but histopathology proved to be gold
standard for its confirmation. All these patients were managed by surgical
excision. The postoperative and follow up period in all the cases was uneventful.
CONCLUSION: It is important to be aware and make a definitive diagnosis of this
rare congenital anomaly as they can present in various clinical forms and can
cause significant morbidity and even mortality if left untreated by causing life
threatening complications.
PMID- 26435953
TI - Bilateral Multifocal Renal Angiomyolipoma Associated with Wunderlich's Syndrome
in A Tuberous Sclerosis Patient.
AB - Renal Angiomyolipoma (renal AML) is a benign clonal neoplasm with a incidence of
0.3-3%, occurring as isolated sporadic entity or in association with Tuberous
sclerosis (TS) in 80% cases. Multiple, bilateral renal AML are considered
diagnostic of Tuberous sclerosis. Wunderlich's syndrome, a urological emergency
is a spontaneous nontraumatic bleeding into subcapsular and or peri-renal space
and is a life threatening complication of renal AML occurring in 10% cases which
has to be timely diagnosed and treated. Here, we present an unusual case of TS
with bilateral, multifocal renal AML in a 25-year-old female who presented with
Wunderlich's syndrome, which is a rare but life threatening complication that has
to be suspected, timely diagnosed and treated. We have discussed the importance
of early diagnosis, timely treatment, follow up and education of patient and
relatives of the possible complications associated.
PMID- 26435954
TI - Intracystic Papillary Carcinoma in Male Breast with High Nuclear Grade: A Case
Report.
AB - Intracystic papillary carcinoma (IPC) in men is an extremely rare disease that
accounts for less than 1% of all malignancies with only a few case presentations
published so far. This report presents a case of 53-year-old male, who presented
a painless swelling of his left breast. The left breast mass was 6 cm maximally
and was found to be non-invasive IPC. The tumour is consistently positive for
GCDFP-15, ER or PR and negative for HER-2. It consists of predominantly
fibrovascular stromal lined by monotonous epithelial cells retaining intermediate
to high histological grade with a high nuclear cytoplasmic ratio. In addition,
increased numbers of mitotic figures were also seen. Chest X-ray, liver
ultrasound and bone centigram showed no evidence of distant metastases. In short,
this is the first case report from Saudi Arabia of a male having IPC, with
increased number of mitotic figures and high nuclear grades.
PMID- 26435955
TI - Hepatoid Adenocarcinoma of the Gall Bladder-A Rare Variant.
AB - Hepatoid adenocarcinoma is a rare variant of extra hepatic adenocarcinoma,
consisting of foci of both adenomatous and hepatocellular differentiation with
morphological and functional resemblance to hepatocellular carcinoma and hence
correct diagnosis is a challenge. The most frequent site is stomach. We present
this case of hepatoid carcinoma of the gallbladder for its rarity and difficulty
in diagnosis which on histology showed papillae, sheets and trabaculae of
polygonal cells with eosinophilic cytoplasm and vesicular nuclei with prominent
nucleoli with adjacent foci showing high grade dysplasia.
PMID- 26435956
TI - Metaplastic Carcinoma of Breast with Extensive Chondroid Differentiation: A Case
Report with Review of Literature.
AB - Metaplastic carcinoma of breast (MBC) is a rare and aggressive type of invasive
breast cancer. As it encompasses a variety of distinct histopathologic
designations, diagnostic challenges abound. We present a case report of
metaplastic carcinoma with extensive chondroid differentiation. This case merits
presentation because of its rarity and difficulty to diagnose, especially if the
tumour is composed mainly of sarcomatous elements. Standard chemotherapy regimes
are ineffective against MBC. The prognosis of MBC is poor in comparison to
classical invasive breast cancer. Data focusing on MBC is limited due to its rare
incidence.
PMID- 26435957
TI - Concurrent Lactating Adenoma and Infiltrating Ductal Carcinoma: A Case Report.
AB - A lactating adenoma is a benign tumour which usually occurs in younger women who
are either pregnant or breast feeding. In some instances these lactating adenomas
can occur simultaneously with breast carcinoma, so they have to be carefully
evaluated. We report an unusual case of simultaneous occurrence of a lactating
adenoma and infiltrating ductal carcinoma occurring in a 25-year-old lactating
mother.
PMID- 26435958
TI - Intra-Arterial Angiolymphoid Hyperplasia with Eosinophilia: A Rare Case Report of
Peripheral Medium Sized Muscular Artery Involvement.
AB - Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign
vasoproliferative disease with distinct clinical and histopathological features.
The most common clinical presentation is dermal and subcutaneous painless nodules
in the head and neck region. The involvement of medium sized peripheral muscular
artery is uncommon. It predominantly affects Caucasian adults during the third
and fourth decades, but is also known to occur in Asians and it very rarely
occurs in children. We here by present a case of intravascular ALHE in a 46-year
old female presenting with subcutaneous forearm nodule clinically diagnosed as
ulnar artery thrombosis.
PMID- 26435959
TI - Bilateral Cystic Lymphangioma of Ovary Associated with Chylous Ascites.
AB - Intraabdominal cystic lymphangiomas are rare and are located in retroperitoneum,
mesentery, omentum and other visceral organs. Lymphangiomas of the ovary are rare
and are usually unilateral. Cases with bilateral cystic lymphangiomas of the
ovary are reported very rarely in literature. We report a rare case of bilateral
cystic lymphangioma of ovary associated with chylous ascites in a 35-year-old
lady who presented with complaints of severe dysmenorrhoea and oligomenorrhoea
since 6 months with history of chyluria for the past 3 years.
PMID- 26435960
TI - Clear Cell Hidradenoma of the Ear Lobule: An Unusual Site of Presentation.
AB - The origin of hidradenoma was from the eccrine sweat glands, generally found in
the head, face, and upper extremity regions. This lesion has not been reported to
be large enough to present in the ear lobule. Hence, its description in the
otolaryngology literature is extremely rare. The rarity of this neoplasm and
failure to identify its morphologic features may lead to misdiagnosis. We present
a benign clear cell hidradenoma of the right ear lobule in a 45-year adult male.
We encountered a tumour measuring 4 cm in diameter. Mass shows ulcerated surface,
bleeds on touch and remained a diagnostic dilemma till an excision biopsy was
carried out and a histopathological report confirmed that it was a hidradenoma of
clear cell variant. The aim of presenting this case report was interesting in the
fact that it has added clear cell hidradenoma in the final diagnosis, in an
uncommon site of presentation.
PMID- 26435961
TI - Adult Multicystic Nephroma: Case Report and Review of the Literature.
AB - Multicystic nephroma (MCN) is relatively a rare, nongenetic and benign lesion of
the kidney which has a bimodal distribution. The congenital form is commonly seen
under the age of 2. Adult-onset MCN is more often seen in women, especially in
post menopausal females. The aetiopathogenesis of MCN is still unknown. Ovarian
like stroma of the tumour indicates the tumour originates from the mullerian
tissue of the kidney. Hormonal theory is suggestive as the stroma of the tumour
is positive for estrogen and progesteron. Preoperative diagnosis of MCN is
difficult. Surgical approach is recommended both for the histological diagnosis
and the treatment of the disease. We here present a 53-year-old female patient
with MCN admitted to the urology clinic with left flank pain treated successfully
with partial nephrectomy. No recurrence was noted after six months of clinical
and radiological follow-up.
PMID- 26435962
TI - A Survivor of Neonatal Intestinal Mucormycosis.
AB - Gastrointestinal mucormycosis (GIM) is a rare opportunistic fungal infection. One
third of all patients are children and of these, 50% are infants. The most common
clinical mimic is necrotizing enterocolitis (NEC). It has to be differentiated
from this entity as the treatment is entirely different. High index of suspicion
by the clinicians and the pathologists aids in early diagnosis and immediate
treatment. If untreated, it has a frequent fatal outcome. Very few survivors of
GIM are found in literature. We report a rare case of a surviving neonate of GIM.
PMID- 26435963
TI - Prediabetes Awareness and Practice Among Indian Doctors- A Cross-sectional Study.
AB - INTRODUCTION: Prediabetes is an intermediate state between diabetes and
normoglycaemia, where the glucose levels are higher than normal but not
significant to be diagnosed as diabetes mellitus. Guidelines from various
associations suggest different types of management in this situation. OBJECTIVE:
To assess knowledge and attitude of the doctors regarding prediabetes using
questionnaire. MATERIALS AND METHODS: A cross-sectional questionnaire based study
was conducted to assess the knowledge, attitude and practice among doctors
regarding prediabetes treatment. One hundred twenty two (of 150) filled
questionnaires were received from general practitioners, post graduates (PGs),
physicians and super specialists in and around Kolar and Bangalore. Data was
analysed using descriptive statistics and expressed as percentage. RESULTS: A
total of 81.3% responded to the questionnaire, of which 14 were general
practitioners (MBBS), 48 PGs in General Medicine, 46 physicians (MD General
Medicine), and 14 super specialists (DM). Knowledge response was 85.7%
(definition - 100%, prevalence - 50.8%, approved drug- 45.2%, progression-
86.2%). Screening for prediabetes was done by 71% of the general practitioners
and physicians, but specialists would screen all. 100% general practitioners,
97.9% post graduates, 91.3% of physicians and 64.2 % specialist preferred diet
and exercise and rest of them opted for oral antidiabetic drug (OAD) along with
diet and exercise, but none of the doctors considered OAD alone for prediabetes.
Among OADs metformin (77.45%) was the most preferred followed by voglibose
(20.6%) and sitagliptin (1.9%). CONCLUSION: All doctors had awareness of
prediabetes and most of them would regularly screen and treat prediabetes.
Majority considered diet and exercise as first modality of treatment. The OAD
opted commonly was metformin.
PMID- 26435964
TI - An Experimental Study to Evaluate the Effect of Memantine in Animal Models of
Anxiety in Swiss Albino Mice.
AB - BACKGROUND: Due to the adverse effects produced by the present conventional
medicines for anxiety disorders, research for newer drugs is still desirable.
From the literature it is evident that NMDA receptors play a key role in animal
models of anxiety. AIM: The present study is done to evaluate the antianxiety
effect of memantine in swiss albino mice. MATERIALS AND METHODS: The experimental
study was conducted from November 2014 to January 2015. Animals were divided into
four groups. Twelve mice were randomly allotted in each group. Animals in the
first group received normal saline as a control 10ml/kg, lorazepam 0.5mg/kg was
administered to second group, memantine 3mg/kg as a test drug was given to the
third group and memantine 3mg/kg + lorazepam 0.5mg/kg was administered to the
fourth group. All the drugs were given for 7 consecutive days by intraperitoneal
route. RESULTS: Results were analyzed by one-way ANOVA followed by Post-hoc
Tukey's test. On the 1(st) day, memantine treated group did not show statistical
significant anxiolytic effect in both the behavioural paradigms when compared to
control group. On the 8(th) day, the animals showed significant decrease p<0.001
in step down latency period in shock free zone (185.4+/-3.87 Vs 278.3+/-5.49),
significant increase p<0.001 in step down errors (6.8+/-0.78 Vs 1.4+/-0.19) and
significant increase p<0.001 in total time spent in shock zone (32.1+/-2.22 Vs
5.6+/-0.6). In open field test, on 8(th) day the animals treated with memantine
when compared to control group, showed significant increase p<0.001 in number of
squares crossed (112.7+/- 2.69 Vs 83.2+/-2.96), time spent in central square
(11.5+/-1.26 Vs 3.4+/-0.65), no. of rearings (32.4+/-2.61 Vs 17+/-1.81) and
significant decrease p<0.001 in freezing time (15.2+/-1.12 Vs 20.2+/-2.29).
Memantine showed synergistic antianxiety effect when combined with lorazepam.
CONCLUSION: Memantine showed significant anxiolytic effect in open field and
passive avoidance response tests which are commonly used experimental models to
assess anxiety states in animals.
PMID- 26435965
TI - Intrauterine Fetal Death in Gunshot Injury to the Gravid Uterus: Forensic
Perspective.
AB - Assault on pregnant women is not a rare event; however forensic analysis of
gunshot injuries among the same group requires a greater deliberation. This is
the report of a 38-week-old fetus which succumbed following gunshot injuries to
the mother while the latter survived. The uniqueness of fetal injuries in the
form of avulsed wound with complete detachment of anus is of great forensic
interest. Such unusual wound pattern could have been the result of a blast wave
effect created due to the high velocity projectile affecting the fluid filled
uterine cavity.
PMID- 26435966
TI - An Audit of VDRL Testing from an STI Clinic in India: Analysing the Present
Scenario with Focus on Estimating and Optimizing the Turnaround Time.
AB - BACKGROUND: Timeliness of reporting is of utmost importance to limit the spread
of syphilis. The present analysis was undertaken to evaluate the turnaround time
of syphilis testing (mainly Venereal disease research laboratory /VDRL test) in a
sexually transmitted infections (STI) clinic in India; to find out the possible
reasons for delay; to describe the trends of clinical indications for syphilis
testing from an STI clinic; to assess the frequency of a positive syphilis
serology among STI clinic attendees; and to analyse the follow-up rates of VDRL
report collection. MATERIALS AND METHODS: Two hundred consecutive VDRL requests
received at the serology laboratory of a tertiary care health facility from the
STI clinic of the linked hospital were prospectively analysed to evaluate the
above parameters. RESULTS: For the 200 requests audited, the mean absolute
turnaround time of VDRL test was 7.46+/-2.81 days. The mean duration of the pre
laboratory, laboratory and post laboratory phases was 0, 4.69+/-2.13 and 2.77+/
2.51 days respectively. The interval from specimen receipt to performance of
tests (mean duration=4.25+/-1.96 days) was the major reason for long VDRL
turnaround time. The common indications for syphilis testing in STI clinic
attendees were lower abdominal pain (33%), vaginal discharge (26.5%) and genital
ulcer disease (9%); and the follow-up rate for report collection was 71%.
CONCLUSION: Our study highlights the strong need to shift to alternative testing
methods, mainly rapid point of care procedures for serodiagnosis of syphilis in
order to circumvent the problems of long turnaround time and low patient follow
up rates.
PMID- 26435967
TI - Assessment of Critical Care Provider's Application of Preventive Measures for
Ventilator-Associated Pneumonia in Intensive Care Units.
AB - BACKGROUND: The implementation of guidelines for the prevention of Ventilator
associated pneumonia has been shown to have a significant effect in reducing the
incidence of VAP. OBJECTIVE: The aim of the present study was to evaluate the
implementation of the preventive strategies for VAP in ICUs of university
hospitals of Sari, Iran. MATERIALS AND METHODS: This cross-sectional study was
carried out in 600 beds/day in the ICUs of university hospitals of Sari from
April to June 2012. Sampling was done by availability technique in patients
receiving mechanical ventilation in the ICU. The implementation of the preventive
measures was assessed by a standard checklist with previously approved validity
and reliability. RESULTS: The percentage of implementing each of the measures was
as follows: sterile suction, 88.44%; semi-recumbent position, 76.8%; oral
hygiene, 58.45%; using heat and moisture exchanges (HMEs), 58%; controlling cuff
pressure, 46.8%; hand hygiene, 32.8%; using anti-coagulants, 26.8% and
physiotherapy, 25.5%. Closed suction system, continuous drainage of subglottic
secretions and kinetic beds were not used at all. CONCLUSION: The overall mean
percentage of implementing preventive measures was low and required designing
integrated guidelines by considering the conditions of the ICUs in each country,
as well as educating and encouraging the staffs to use the recommended
guidelines.
PMID- 26435968
TI - Dr. A.P.J Abdul Kalam-"A Man Beyond Science".
PMID- 26435969
TI - Peer Teaching to Foster Learning in Physiology.
AB - INTRODUCTION: Peer teaching is an effective tool to promote learning and
retention of knowledge. By preparing to teach, students are encouraged to
construct their own learning program, so that they can explain effectively to
fellow learners. Peer teaching is introduced in present study to foster learning
and pedagogical skills amongst first year medical under-graduates in physiology
with a Hypothesis that teaching is linked to learning on part of the teacher.
MATERIALS AND METHODS: Non-randomized, Interventional study, with mixed methods
design. Cases experienced peer teaching whereas controls underwent tutorials for
four consecutive classes. Quantitative Evaluation was done through pre/post test
score analysis for Class average normalized gain and tests of significance,
difference in average score in surprise class test after one month and percentage
of responses in closed ended items of feedback questionnaire. Qualitative
Evaluation was done through categorization of open ended items and coding of
reflective statements. RESULTS: The average pre and post test score was
statistically significant within cases (p = 0.01) and controls (p = 0.023). The
average post test scores was more for cases though not statistically significant.
The class average normalized gain (g) for Tutorials was 49% and for peer teaching
53%. Surprise test had average scoring of 36 marks (out of 50) for controls and
41 marks for cases. Analysed section wise, the average score was better for Long
answer question (LAQ) in cases. Section wise analysis suggested that through peer
teaching, retention was better for descriptive answers as LAQ has better average
score in cases. Feedback responses were predominantly positive for efficacy of
peer teaching as a learning method. The reflective statements were sorted into
reflection in action, reflection on action, claiming evidence, describing
experience, and recognizing discrepancies. CONCLUSION: Teaching can stimulate
further learning as it involves interplay of three processes: metacognitive
awareness; deliberate practice, and self-explanation. Coupled with immediate
feedback and reflective exercises, learning can be measurably enhanced along with
improved teaching skills.
PMID- 26435970
TI - The Use of Ice Pack for Pain Associated with Arterial Punctures.
AB - BACKGROUND: Arterial punctures for monitoring respiratory problems are one of the
most painful procedures in hospitalized patients. The knowledge regarding non
pharmacologic methods of pain management, including cold application is limited.
OBJECTIVE: This aim of this study was to determine if the application of ice pack
before the procedure would decrease the pain perception of patients during the
arterial puncture. MATERIALS AND METHODS: This experimental study was undertaken
among patients admitted to emergency ward in a public educational center
affiliated to Ilam University of Medical Sciences, Ilam/Iran. Sixty-one eligible
subjects were randomly assigned to two groups. The treatment group (n=31)
received ice pack before arterial puncture, whereas the control group (n=30)
received no intervention for pain management. Pain immediately and 5 minute after
the arterial puncture were scored on a visual analog scale (VAS) from 0 to 10.
RESULTS: The mean of pain score immediately after the arterial puncture were 3.12
(1.68) and 4.6 (1.56) for treatment and control group, respectively (p<0. 001).
The mean pain score 5 minute after the punctures were 1.9 (1.51) for treatment
group and 2.53 (1.85) for control group. This difference was not statistically
significant. The mean of heart rate during the procedure were 75.45 (9.76)
beats/min for the treatment subjects and 75.46 (9.36) beats/min for the control
group (p>0.05). Patients with previous arterial puncture reported higher pain
intensity. CONCLUSION: Cold pack is a simple, non-invasive and inexpensive
technique for pain management before the arterial puncture. However, there is a
need for further research regarding this topic.
PMID- 26435971
TI - Ophthalmology Teaching-Learning in Undergraduate Classes: Roadblocks and The
Remedies.
AB - The curriculum needs to run apace with the changing morbidity pattern and social
needs. Teaching methodology requires constant evolution. With a static curriculum
and teaching methods undergraduate ophthalmology proves difficult for many
students. This article briefly analyses the ophthalmology curriculum, highlights
the problems of teaching and offers some solutions.
PMID- 26435972
TI - Evaluation of Dietary Choices, Preferences, Knowledge and Related Practices Among
Pregnant Women Living in An Indian Setting.
AB - INTRODUCTION: Healthy and nutritious diet is very essential component of
Antenatal care along with clinical advice. The objective of this study was to
understand the dietary choices, preferences, knowledge and related practices
among pregnant women living in an Indian setting. MATERIALS AND METHODS: Hundred
pregnant women were enrolled in this cross-sectional study. Information about
Socio-demographic profile, food item price and approach during inflation,
nutrition related knowledge, attitude and practices and 24 hour dietary recall
was acquired. RESULTS: Majority of the participants (87%) reported regular
antenatal care visits and intake of iron and folic acid tablets. Eighty two
percent of the participants were acquainted with standardized marks on food items
and 64% of them reported checking of these marks before purchasing. Thirty two
percent of the participants did not know about balanced diet. Fifty eight percent
of the participants felled in fair category of dietary recall final scores.
CONCLUSION: There is still vast room for improvement of the nutritional status of
pregnant women as none of the participants were able to achieve excellent status
on 24 hour food record scoring sheet.
PMID- 26435973
TI - Pubertal Timing and Demographic Predictors of Adolescents in Southwest Nigeria.
AB - BACKGROUND: Changes in the timing of puberty have been an area of research
interest in developed countries because of its associated health and psychosocial
problems. Adolescents in Africa are no exception as they are reaching adulthood
today much earlier than before. This changing trend may have a major influence on
adolescents' sexual behaviour. AIM: This study determined the timing of puberty
and demographic predictors among the adolescents in southwest Nigeria. MATERIALS
AND METHODS: The study was a cross-sectional study. Using Modified Sexual
Maturity Scale (MSMS) of pubertal assessment, data were collected from 1000
respondents from rural and urban areas of Osun state, Nigeria. Data were
collected using pre-tested Assisted Self Completion Questionnaires (ASCQ). The
rate of pubertal development was based on age group and current pubertal stage.
Data were analysed using SPSS version 16. Chi-square and logistic regression
analyses were done to identify significant demographic predictors. Statistical
significance was at 5% level. RESULTS: The overall mean age of the respondents
was 14.22+/-2.47 years. The mean age for males was 14.19+/-2.38 years and 14.25+/
2.57 years for females. A total of 52.9% of the respondents were males and 47.1%
were females. Higher proportions of the females, 41.6% were already in late
puberty stages compared to their male counterparts where 21.9% were at this
stage. With regards to this rate of pubertal development, more males, 14.2%
significantly had late rate of pubertal development than the females 5.1%. The
significant demographic predictors was socio-economic class in females only.
CONCLUSION: From this study, the timing of puberty was early for females and
socio-economic class is an important demographic predictor for pubertal
development. This study was however limited because intrinsic factors such as
genetic makeup and nutritional status which could affect the finding were not be
excluded.
PMID- 26435974
TI - Ganglioneuroblastoma of Skull Base.
AB - Neuroblastic tumours are common in childhood and adrenal glands are the most
common site. Head and neck ganglioneuroblastomas are extremely rare and nose is a
very uncommon site for a ganglioneuroblastoma. The management of this primitive
sympathogonic tumour may vary depending on the age of the patient and stage of
the tumour. We present a middle-aged man with a ganglioneuroblastoma of skull
base, management of this tumour and a review of literature.
PMID- 26435975
TI - Is There a Critical Period for Amblyopia Therapy? Results of a Study on Older
Anisometropic Amblyopes.
AB - PURPOSE: Amblyopia, a common cause of low vision, is rarely treated in adults.
Improvement in vision has been seen beyond the critical period at times. Hence,
this study was taken up to study the effect of minimal occlusion therapy (2-4
hours/day) in anisometropic amblyopic patients in the age group of 12-30 years.
MATERIALS AND METHODS: The study is a prospective, randomized case series of
anisometropic amblyopia patients aged 12-30 years who reported in the outpatient
department of Hakeem Abdul Hameed Centenary Hospital, New Delhi, from December
2011 to November 2013. Thorough ocular examination and cycloplegic refraction was
done to rule out other ocular disease. Anisometropic Amblyopia was diagnosed only
after four weeks of spectacle wear. The selected patients were then advised
occlusion therapy of 2-4 hours per day of better eye with stress on near visual
task. Videogames, computers, mobile phone gaming and colouring in especially
designed patterns were used as vision training aids. The outcome measure selected
was best corrected visual acuity (BCVA) achieved that remained stable for three
consecutive months of occlusion. RESULTS: Sixty one patients of anisometropic
amblyopia were included in the study (32 males and 29 females) aged 12-30 years
(mean age 17 years). Mean BCVA at the start of treatment was 20/125 (0.8 log MAR
units) and 20/32 (0.2 log MAR units) at the end of the treatment. Thirty three
patients (54%) out of 61 had BCVA of 20/20, while 58 patients (95%) had >= 20/40
BCVA, 01(1.6%) had 20/50 and 02 (3.27%) had 20/80 BCVA at the end of therapy. The
results were statistically significant (p- value <0.0001) with a 95% confidence
interval. CONCLUSION: This study clearly proves that there is no critical period
for the treatment in older (12-30 years) anisometropic amblyope. Even 2-4 hours
per day of occlusion of better eye with vision training thorough near visual task
of amblyopic eye is effective. However, counseling and patient compliance is
important for successful outcome of therapy.
PMID- 26435976
TI - Potential for Hospital Based Corneal Retreival in Hassan District Hospital.
AB - CONTEXT: In developing countries, corneal diseases are the second leading cause
of blindness. This corneal blindness can be treated through corneal
transplantation. Though the present infrastructure is strong enough to increase
keratoplasty numbers at a required rate, India has largest corneal blind
population in the world. So a constant supply of high quality donor corneal
tissue is the key factor for reduction of prevalence of corneal blindness.
Considering the magnitude of corneal blindness and shortage of donor cornea,
there is a huge gap in the demand and supply. AIM: To study the potential for
hospital based retrieval of donor corneal tissue in Hassan district hospital
after analysing the indicated and contraindicated causes of deaths, so that
hospital corneal retrieval program in Hassan district hospital can be planned.
MATERIALS AND METHODS: The cross-sectional, retrospective and record-based study
included all hospital deaths with age group more than two years occurred during
one year period (January 2014 to December 2014). Data regarding demographic
profile, cause of death, treatment given and presence of any systemic diseases
were collected. The causes of deaths which are contraindicated for the retrieval
of corneas were analysed and noted. The contraindications were based on the NPCB
guidelines for standard of eye banking in India 2009. RESULTS: Out of 855 deaths,
number of deaths in males (565) was greater than females (290). Numbers of deaths
were highest between 41-60 years age group (343). Deaths due to HIV, septicaemia,
meningitis, encephalitis, disseminated malignancies were contraindicated for
corneal retrieval. Corneas could be retrieved from 736 deaths out of 855.
Potential for corneal retrieval in a period of one year in Hassan District
hospital was 86%. CONCLUSION: Hospital corneal retrieval program has got a great
potential to bridge the gap between the need for the cornea and actually
collected corneas which will contribute enormously in eliminating corneal
blindness. In present study there was 86% potential for corneal retrieval among
the hospital deaths.
PMID- 26435978
TI - Tubercular Nodular Episcleritis: A Case Report.
AB - Tuberculosis (TB) is an infectious disease caused by the acid-fast bacillus
Mycobacterium tuberculosis and is an important cause of death worldwide.
Tuberculosis most commonly affects the lungs, but has many extrapulmonary
manifestations as well, including intraocular involvement. Tubercular nodular
episcleritis is a very rare presentation and no such case in an adult male has
been reported in the literature. Herein, we present the very first case of
tubercular nodular episcleritis in a 30-year-old Indian male.
PMID- 26435977
TI - Evaluation of Choroidal Thickness and Volume during the Third Trimester of
Pregnancy using Enhanced Depth Imaging Optical Coherence Tomography: A Pilot
Study.
AB - BACKGROUND: During pregnancy the maternal choroid is exposed to the multiple
haemodynamic and hormonal alterations inherent to this physiological condition.
These changes may influence choroidal anatomy. In this study a quantitative
assessment of overall choroidal structure is performed, by constructing a 3
dimensional topographic map of this vascular bed. PURPOSE: To compare the
thickness and volume of the maternal choroidal in the third trimester of
pregnancy with that of an age-matched control group of women. MATERIALS AND
METHODS: Twenty-four eyes of 12 pregnant women in the last trimester and 12 age
matched healthy controls (24 eyes) were included. Optical coherence tomography in
enhanced depth imaging mode was used to construct maps of the choroid of the
macular area. Choroidal thickness and volume were automatically calculated for
the 9 subfields defined by the Early Treatment Diabetic Retinopathy Study
(ETDRS). A comparative analysis between the two groups was performed using the
two-way ANOVA test. RESULTS: The average thickness of the choroid for the entire
ETDRS area of the pregnant group was 295.15 +/-42.40MUm and 271.56 +/-37.65MUm in
the control group (p=0.051). The average choroidal volume was 8.05 +/-1.12mm(3)
and 7.46 +/-1.03mm(3), respectively (p=0.067). Although the choroid of the
pregnant group had larger thickness and volume in all subfields compared to the
control group, this difference was statistically significant only in three
regions - the central subfield, minimum foveal thickness and inferior inner
macula (p<0.05). CONCLUSION: Our study suggests that in the third trimester of
pregnancy the choroid may be subjected to physiological changes in structure.
Whether these changes are a result of hormonal and/or haemodynamic adaptations of
pregnancy remains to be studied.
PMID- 26435979
TI - Unexplained Anterior Uveitis: Viral Causes.
PMID- 26435980
TI - Correlation between Six Minute Walk Test and Spirometry in Chronic Pulmonary
Disease.
AB - INTRODUCTION: Six minute walk test (6MWT), is an exercise test, used as a
clinical indicator of the functional capacity, in patients with cardiopulmonary
diseases. The present study assessed the correlation of six minute walk test with
pulmonary function variables, in patients with chronic pulmonary diseases, in
local population. AIMS & OBJECTIVES: The objectives were to study correlation of
different spirometry variables with variables of six minute walk test like
percent predicted 6 minute walk distance (% Predicted 6MWD) as per Enright et
al., formula and Indian reference equation, pre and post exercise pO2 and pCO2
and exercise desaturation. MATERIALS AND METHODS: All consecutive patients with
confirmed diagnosis of chronic pulmonary diseases were included from January 2013
to June 2014 in tertiary care institute. 6MWT was performed as per the ATS
guidelines. Among 130 patients 108 were also subjected to arterial blood gases
pre and post test. Spirometry was performed as per ATS guidelines. Percent (%)
predicted 6MWD was calculated. Correlation between spirometry and 6MWT was
assessed. RESULTS: One hundred and thirty patients with chronic pulmonary disease
were taken. Out of them there was 102 patients with obstructive airway disease
and 58 patients with interstitial lung disease. FEV1 significantly correlated
with %predicted 6MWD &; with basal pO2 and pCO2 and with post exercise pCO2 and
pO2. FVC also correlated with %predicted 6MWD, with basal pO2 and pCO2 and post
exercise pO2. FEV1/FVC correlated only with post exercise pCO2 while MVV
correlated with %predicted 6MWD and only basal pCO2. Exercise desaturation
correlated only with FVC. Percent predicted 6MWD also correlated with basal pO2 &
post exercise pO2. CONCLUSION: Thus significant correlation found between 6MWT &
spirometry variables (FEV1, FVC, MVV & FEV1/FVC).
PMID- 26435981
TI - Pattern of Use of Antibiotics Following Snake Bite in a Tertiary Care Hospital.
AB - INTRODUCTION: There are several conflicting recommendations on the use of
antibiotics in snakebite victims. This study aimed to identify the pattern of
antibiotics used following snake envenomation in a tertiary care hospital of
Kerala. MATERIALS AND METHODS: Retrospective review of case records from January
to August 2011 was done and all the cases filed as snakebite were reviewed and
details entered in a structured performa. Data was analysed using SPSS 16 and
results were expressed mainly using descriptive statistics. RESULTS: Three
hundred and thirteen cases were evaluated with mean age 37.58+/- 14.54 year and
51.1% were males. Out of total, 94.6% received antibiotics of which 88.85% were
oral, 8.1% parenteral and 3.04% both. There were total 454 prescriptions of
antibiotics. In all seven different types of antibiotics were prescribed alone or
in combination of which Ampicillin (205) was the commonest followed by
Cloxacillin (194). The mean antibiotic usage was 1.46+/-0.716 per patient and the
mean duration of antibiotic use was 3.16+/-1.446 days. In patients with no
envenomation the mainly prescribed antibiotic was Cloxacillin (126). Intravenous
antibiotics like Piperacillin plus Tazobactam were given only in patients with
either local or systemic envenomation. CONCLUSION: The main pattern of use of
antibiotics following snakebite envenomation is Ampicillin alone or in
combination empirically, Cloxacillin prophylatically and Piperacillin with
Tazobactam for severe established infections. The choice of antibiotics is based
on the clinician's discretion. Since the study setting is in a developing country
the prophylactic use of antibiotics may be justified weighing the concerns of
secondary infections.
PMID- 26435982
TI - Short Term Safety and Tolerability of a Fixed Dose Combination of Olmesartan,
Amlodipine and Hydrochlorothiazide.
AB - OBJECTIVE: To assess the short term safety and tolerability of a fixed dose
combination (FDC) of olmesartan, amlodipine and hydrochlorothiazide (OAH) in real
world clinical setting in India. MATERIALS AND METHODS: Physicians were requested
to provide eight weeks observational clinical event data of the patients
prescribed with FDC of Olmesartan (20/40mg), Amlodipine (5mg) and
hydrochlorothiazide (12.5mg) in the prescription event monitoring (PEM) forms.
Data on patients' demographics, indication for FDC, concomitant medication and
other relevant history was also collected and was analysed with descriptive
statistics. RESULTS: Two hundred thirty eight physicians provided data of 4763
patients. Mean age of the population was 55+/-7 years and males were 59.3%. The
commonest indication for the FDC was uncontrolled hypertension (60.7%). Diabetes
and dyslipidemia were present in 37.9% and 35.1% respectively. Concomitant
medications included statins (42.3%), oral anti-diabetic (33.7%) and antiplatelet
agents (24.7%). Pedal oedema (0.29%) was the most common adverse event (AE)
reported followed by headache (0.16%), giddiness (0.15%), light headedness (0.15)
and stroke (0.15%). Other less common (0.04%) reported AEs were tiredness,
dizziness, gastritis, hypersomnia, hypoglycaemia, lower respiratory tract
infection (LRTI), weakness, diarrhea, labyrinthitis, urinary tract infection,
hyponatremia and hypotension. Occurrence of AEs was more common in patients with
uncontrolled hypertension (60.74%). CONCLUSION: The FDC of olmesartan, amlodipine
and hydrochlorothiazide prescribed most frequently for patients with uncontrolled
hypertension and co-morbidities was found to be safe and well tolerated over a
short period of observation.
PMID- 26435983
TI - HIV Status Disclosure Among People Living with HIV in the Era of Combination
Antiretroviral Therapy (cART).
AB - INTRODUCTION: As patients with HIV live longer due to Combination Anti-Retroviral
Therapy (cART) serostatus disclosure becomes an important issue. Disclosure can
have both positive and negative outcomes. Disclosure of HIV status has been
associated with better adherence to medication and reduction in levels of
psychological distress. Stigma and disruption of family relationships are
barriers for disclosure. Most studies regarding disclosure status have been
conducted in West. There are many cultural differences in Indian society when
compared to west. There is a dearth of research in the field of disclosure of HIV
infection in India. AIM: To determine the prevalence of HIV status disclosure
among people living with HIV (PLHIV) in South India. MATERIALS AND METHODS: This
descriptive cross-sectional study was done in the hospital attached to Kasturba
Medical College (KMC), Mangalore, India from May-June 2013. PLHIV of age more
than 18 years were included. During the study period 111 consecutive patients who
consented for the study were enrolled. STATISTICAL ANALYSIS: Data was collected
using a pre-tested interviewer administered semi structured questionnaire. Data
collected was analysed using SPSS Version 11.5 statistical software. Descriptive
statistics were done and the results are presented as proportions and mean.
RESULTS: The mean age of the study population was 44.86 +/- 10.8 years. Majority
of the study subjects were men 76 (68.4%). Out of 111 study subjects, 102 (91.9%)
had disclosed their HIV status to at least one person while 9 (8.1%) had not
disclosed their HIV status to anyone. Disclosure on doctor's advice was the main
reason for 56 (54.9%) participants to disclose their HIV status. The main reason
for non-disclosure was fear of shame in family. CONCLUSION: Disclosure rate was
high in our study in the era of cART. Society must stop discriminating against
PLHIV so that they can disclose their serostatus and gain access to care and
treatment services without any fear of stigma. In our study the main reason for
disclosure was doctor's advice which clearly states the importance of the
commitment of doctors in creating awareness among PLHIV about the need for
voluntary disclosure.
PMID- 26435984
TI - Risk Factors Affecting the Prognosis in Patients with Pulmonary Contusion
Following Chest Trauma.
AB - INTRODUCTION: Thoracic injury and its complications are responsible for as much
as 25% for blunt trauma mortality. Pulmonary contusion occurs in 30%-75% of these
cases. Despite advances in pulmonary care and intensive care management pulmonary
contusion still contributes to higher mortality and morbidity for patients with
severe injuries. AIM: To assess the outcome of pulmonary contusions in patients
with chest trauma and various factors determining mortality in these patients.
MATERIALS AND METHODS: A retrospective case study, over a period of one year, of
all chest trauma cases with pulmonary contusions confirmed by X-rays or CT scan
of thorax, were included in the study. All the cases were assessed for age,
associated injuries, APACHE II score, SAPS II score, SOFA score, paO2/Fio2 ratio,
fracture of ribs, presence of haemothorax or pneumothorax, ventilator and ICU
days and finally hospital outcome. RESULTS: A total of 16 cases of pulmonary
contusions were included in the study. Five patients died during the ICU stay and
11 survived. All patients had associated injuries. There was significant
difference seen in APACHE II score (p<0.001), SAPS II score (p<0.001), SOFA score
(p<0.001), paO2/Fio2 ratio (p<0.022) and ventilator days (p<0.001) among the
survivors and non-survivors. However, no significant difference was seen in
presence of fracture of ribs and presence of either haemothorax or pneumothorax.
CONCLUSION: The risk factors that were associated with higher mortality in
patients with pulmonary contusions following chest trauma were APACHE II score,
SAPS II score, SOFA score, paO2/Fio2 ratio and ventilator days. Close monitoring
to improve the gas exchange and better fluid management will help in improving
the survival in these patients.
PMID- 26435985
TI - Study on Diastolic Dysfunction in Newly Diagnosed Type 2 Diabetes Mellitus and
its Correlation with Glycosylated Haemoglobin (HbA1C).
AB - INTRODUCTION: Left ventricular diastolic dysfunction (LVDD) represents the first
stage of diabetic cardiomyopathy preceding changes in systolic function,
reinforcing the importance of early examination of ventricular function in
individuals with diabetes mellitus (DM). This cross-sectional study was conducted
to determine the incidence of asymptomatic LVDD in newly diagnosed normotensive
cases of type 2 diabetes subjects, and its relation to glycosylated haemoglobin
(HbA1C), age at the time of diagnosis, body mass index (BMI) and serum total
cholesterol. AIM AND OBJECTIVE: To study the incidence of left ventricular
diastolic dysfunction (LVDD) and its correlation with HbA1C in normotensive,
newly diagnosed type 2 diabetic patients. MATERIALS AND METHODS: This cross
sectional study was done in western U.P. on 100 patients of newly diagnosed
(within 1 month) type 2 DM between patients 30 and 60 years of age, visiting the
Medicine and Endocrinology outpatient Department of LLRM Medical College, Meerut.
Patients with established type 2 diabetes and already taking antidiabetic
treatment, cardiac diseases like valvular heart disease, ischemic and
hypertensive heart disease, congestive heart failure, cardiomyopathy, renal
failure, chronic pulmonary disease, severe anaemia and haemoglobinopathies were
excluded from the study. These patients were informed about the study and
informed consent was obtained before proceeding with the investigations. Patients
selected were evaluated with relevant investigations like fasting and post
prandial blood sugar, HbA1C level, lipid profile and 2D echocardiography to
assess LVDD. These selected patients were divided in 2 groups; one with left
ventricular diastolic dysfunction (LVDD) and second group of subjects without
LVDD. Various parameters like HbA1C, age, body mass index and serum cholesterol
were evaluated between these 2 groups. Statistical analysis was performed using
Student t-test, Chi-square and Fisher Exact-test. RESULTS: Out of 100 patients 65
were males and 35 females. Mean age of the population was 50.08 +/- 6.32 years.
Overall incidence of LVDD was 41%. Grade 1 LVDD was most common. Mean HbA1C level
of LVDD group was found higher as compared to those without LVDD. CONCLUSION:
LVDD is very common at the time of diagnosis of type 2 DM even in normotensive
patients independent of confounding effect of hypertension, ischemia and BMI.
HbA1C and age, were found to be strong indicators of LVDD in newly diagnosed
cases of Type 2 DM.
PMID- 26435986
TI - Nine-Months Clinical Outcome of Biodegradable Polymer Coated Sirolimus-eluting
Stent System: A Multi-Centre "Real-World" Experience.
AB - BACKGROUND: The main culprit in first-generation drug eluting stents is 'durable'
polymer, whose continuous presence may impair arterial healing and ultimately
have a negative impact on late outcomes. The main enigma behind the biodegradable
polymer usage is its degradation after elution of drug. This reduces adverse
events in unselected patients with complex coronary artery lesions treated with
biodegradable polymer coated sirolimus-eluting stents. AIM: The aim of the
INDOLIMUS-G Registry was to evaluate safety and efficacy of the Indolimus
(Sahajanand Medical Technologies Pvt. Ltd., Surat, India) sirolimus-eluting
stents in large cohorts of unselected patients with complex coronary artery
lesions. MATERIALS AND METHODS: It is a multi-centre, non-randomized
retrospective registry with a clear aim of evaluating safety and efficacy of the
Indolimus sirolimus-eluting stents in consecutive patients enrolled between April
2012 and May 2014. The primary end-point of the study was major adverse cardiac
events (MACE), which is a composite of cardiac death, myocardial infarction (MI),
target lesion revascularization (TLR), target vessel revascularization (TVR) and
stent thrombosis (ST) at the end of follow-up. Clinical follow-up were scheduled
at the end of 30-days, 6-months, and 9-months period. RESULTS: The mean age of
enrolled patients was 52.6 +/- 11.0 years. A total of 1137 lesions were
intervened successfully with 1242 stents (1.09 +/- 0.30 stent per lesion). The
average stent length and diameter was 27.42 +/- 9.01 mm and 3.12 +/- 0.36 mm
respectively. There were 740 (73.40%) male patients, indicating their high
prevalence. Diabetes, hypertension and totally occluded lesions were found in 372
(36.90%), 408 (40.47%) and 170 (16.86%) patients, respectively. This showed that
study also included high risk complex lesions and not ideal recruited lesions.
The incidence of MACE at 30-days, 6-months and 9-months were 3 (0.30%), 18
(1.80%) and 22 (2.20%) respectively. At 9-months, TLR was found in 6 (0.50%)
patients. There were 2 (0.20%) cases of ST, 10 (1.0%) cases of MI and 4 (0.40%)
cases of cardiac death at 9-month follow-up. CONCLUSION: The lower incidence of
MACE, TLR and ST at 9-month follow-up clearly delineates safety and efficacy of
Indolimus SES in large cohorts of unselected patients with complex coronary
lesions.
PMID- 26435987
TI - Purple Urine Bag Syndrome.
AB - Purple urine bag syndrome (PUBS) is a rare disorder seen in elderly persons,
wherein the urinary bag and the tubing turn in to purple colour. It is usually
seen in patients who are on urinary catheters for a long time. Purple coloured
urine occurs due to the accumulation of indigo and indirubin, which are the end
products of tryptophan metabolism due to the action of sulfatases and
phosphatases formed by bacteria like Providencia, Citrobacter, Enterobacter,
Klebsiella etc. We present this interesting phenomenon of purple urine in a young
male who was on prolonged urinary catheterization. The urine culture was positive
for Providencia and constipation was an added risk factor for the purple urine.
The urinary catheter and tubing was changed along with a course of antibiotics
which lead to the normalization of the urine colour.
PMID- 26435988
TI - Paroxysmal Nocturnal Haemoglobinuria Masquerading as Malaria: A Case Report.
AB - Paroxysmal Nocturnal Haemoglobinuria (PNH) is a rare type of acquired Haemolytic
anaemia that is described as a triad of acquired intravascular Haemolysis, venous
thrombosis and anaemia with pancytopenia sometimes due to bone marrow failure.
However the classical triad may not be observed at once and fever due to
leucocytopenia may confuse the clinical picture. Since this is a rare disease,
other epidemiologically common causes may be attributed to the illness. We report
a case of PNH with a rare association of malaria due to Falciparum and Vivax
species which was undiagnosed for 6 years in a young man.
PMID- 26435989
TI - Atrial Fibrillation Due to Over The Counter Stimulant Drugs in A Young Adult.
AB - The usage of over the counter stimulant drugs and energy drinks is increasing on
a day to day basis for various purposes including work, sports and leisure among
individuals in all age groups. Multiple formulations are available in the market
including pills, liquid capsules and drinks in various flavours. Many of them
contain excessively high doses of caffeine along with a variety of stimulant
compounds that have multiple effects in different parts of the human body. The
consumption of such high amounts of caffeine itself has shown to have caused
cardiac arrhythmias in healthy individuals and when it is mixed with a number of
stimulant compounds can be associated with a number of adverse effects in the
human body. However, the awareness of such life threatening complications
associated with these energy drinks does not exist among people who consume it on
a day to day basis. We report a case of 25-year-old Caucasian male with no
significant past medical history for cardiac diseases, no risk factors for atrial
fibrillation, non smoker, occasional alcohol drinker who presents with new onset
atrial fibrillation with rapid ventricular response due to the consumption of
over the counter stimulant energy capsule which had high doses of caffeine.
PMID- 26435990
TI - Ethionamide: Unusual Cause of Hypothyroidism.
AB - Multidrug-Resistant tuberculosis (MDR TB) is major health hazard to the people
living in developing countries. As incidence rate of MDR TB has gone up, its
therapy has become crucial. MDR TB therapy is known to cause multiple adverse
effects however the data related to them is minimal. Hypothyroidism is one of the
important adverse effects which usually manifests with vague symptoms and is
frequently missed. We present a case of 24-year-old woman who was diagnosed to
have MDR TB and started on ethionamide based regimen for same. After 6 months of
therapy the patient had clinical symptoms suggestive of hypothyroidism,
laboratory investigations confirmed it. As ethionamide is an integral component
of MDR TB therapy it was continued and thyroxine replacement therapy was given
with which she improved. Hypothyroidism completely resolved after 2 months of
stoppage of MDR TB therapy suggesting the reversible aetiology of ethionamide.
PMID- 26435991
TI - An Unusual Presentation of Chronic Lymphocytic Leukaemia.
PMID- 26435992
TI - Waist-Hip Ratio in Patients with Acute Myocardial Infarction.
PMID- 26435993
TI - Coronal/Hemicoronal Approach - A Gateway to Craniomaxillofacial Region.
AB - AIMS: The coronal incision with its various modifications provides the most
versatile approach to various areas in the craniomaxillofacial region coupled
with excellent exposure. The aesthetic advantage of a hidden scar in the
hairline, accounts for its continued popularity. The aim of this study was to
review the surgical anatomy, technique and problems of post-operative morbidity
pertinent to coronal approach in various clinical situations such as craniofacial
trauma, tumour resections and reconstructive craniofacial procedures. MATERIALS
AND METHODS: In this study, ten patients who presented to Oral and maxillofacial
surgery department with various craniofacial problems requiring the use of
coronal and hemicoronal approach for treatment were evaluated over a period of
two years. Five patients needed coronal approach and another five underwent the
surgical procedures through hemicoronal approach. This was an observational
study. RESULTS: It was observed that a well-planned and carefully designed
coronal/hemicoronal incision with strict adherence to surgical principles posed
minimal complication during surgery as well as post-operatively. None of the
patients developed infection or heamatoma in the postoperative period. Sensory
nerve deficits along the distribution of supraorbital nerve was observed in four
patients of bicoronal approach and three patients of hemicoronal approach which
completely resolved at the end of six months. Motor nerve weakness was observed
in four patients in immediate postoperative period which gradually improved. But
it persisted in one patient even after six months who had pathology of temporo
orbital region. All the patients had transient alopecia along the line of
incision which improved at the end of six months. No other significant
disadvantages or complications were noted. CONCLUSION: This approach offers
widest accessibility and visibility to the entire upper and middle one third of
the face in less than twenty minutes as observed in our study. The postoperative
complications are minimal, minor and outweigh the advantages for surgical
treatment in any given clinical situation as observed in this study. This proves
the brilliance of coronal approach in solving an array of surgical problems
pertinent to craniomaxillofacial region with superior aesthetic outcomes.
ABBREVIATIONS: ZMC-Zygomatico maxillary complex, NOE-Nasoethmoidal complex, LF
Lefort, ORIF-open reduction internal fixation.
PMID- 26435994
TI - Study on Surgical Management of Post Burn Hand Deformities.
AB - CONTEXT: Functionality of the hands is the major determinants of the quality of
life in burns survivors. If contractures or scarring affect the dominant hand, as
they do on most occasions, the vocation and there by the economic status of the
patient suffer. AIM: The aim of this study is to evaluate the different surgical
procedures for resurfacing after release of post-burn hand contractures in terms
of functional recovery and aesthetic outcome. SETTINGS AND DESIGN: It's a
prospective, non-randomised study of 50 patients admitted and undergoing surgical
reconstructive procedures for post burn hand contractures in our plastic surgery
department. MATERIALS AND METHODS: Resurfacing procedures were done according to
type of contracture with individualisation for each case. All cases were followed
up with physiotherapy and splinting advices. Functional and aesthetic outcome and
recurrence of contracture for each procedure was noted at 6 months. RESULTS:
Forty seven percent of the cases were reconstructed with skin grafting, 30% cases
with Z plasties and 23% with flap coverage. Split thickness skin grafts (STSG)
and full thickness graft (FTSG) reconstructed cases had good recovery of joint
mobility in 43% and 75% of cases respectively. Reconstructive procedures were
aesthetically acceptable to the patients in 63%, 75% and 94% of STSG, FTSG and Z
plasty cases respectively. Recurrence was seen in 17% of STSG done cases.
CONCLUSION: Most of the cases can be resurfaced with skin grafting and few cases
have clear indication for flap coverage which needs to be planned and executed
cautiously. Z plasties with proper planning gives maximum length gain with no
donor morbidity as other procedures. Postoperative physiotherapy and splinting is
must for better outcome in all cases.
PMID- 26435995
TI - Osteoplastic Reconstruction for Post Traumatic Thumb Amputations Around
Metacarpophalangeal Joint.
AB - INTRODUCTION: Loss of a thumb due to trauma warrants replantation which is the
best method of reconstruction. When replantation is not possible, thumb
reconstruction is the procedure of choice. The level of thumb amputation guides
the type of reconstruction. There are five goals for reconstructing a thumb:
restoration of (1) functional length (2) stability (3) mobility (especially
opposition) (4) sensibility and (5) aesthetic appearance. AIM: This study was
conducted to evaluate the functional outcome of two main techniques of
osteoplastic thumb reconstruction (1) Osteocutaneous distally based radial
forearm flap (2) Groin flap with iliac crest bone graft. MATERIALS AND METHODS:
Total 13 patients underwent osteoplastic reconstruction in the duration from
August 2012 to December 2014. Thumb reconstruction was done using distally based
radial forearm osteocutaneous flap in 7 patients and two staged reconstruction by
groin flap with iliac crest bone graft in 6 patients. Postoperatively results
were assessed in terms of range of motion, hand grip, functional recovery, donor
site morbidity and patient satisfaction. RESULTS: All reconstructive thumbs were
functionally acceptable. Cosmetically, donor site morbidity was an issue for 2
patients with radial forearm flap and 1 patient with groin flap. Suture line
dehiscence and plate exposure required intervention in local anaesthesia in one
patient with radial forearm flap. After reconstruction absence of pain,
temperature and touch sensation were observed. CONCLUSION: We suggest that
osteoplastic reconstruction is a reliable procedure in terms of stability,
length, strength and opposability if basal joint is intact. Most of the patients
in this study were manual labourers who went back to previous occupation and were
able to use their thumb for daily activities for earning livelihood.
PMID- 26435996
TI - Large Cervical Paraspinal Haemangioma in Association with Intraosseous
Haemangioma: A Rare Case Report.
AB - Haemangiomas are most commonly found in skin and subcutaneous tissue and are very
rare in intramuscular region. Paraspinal musculature has been barely reported as
location of intramuscular haemangioma while we could not find any literature
reporting haemangioma in cervical paraspinal previously. We report a case of
middle aged woman with a large intamuscular haemangioma involving left cervical
paraspinal musculature extending from suboccipital region to C5 vertebra and
reaching upto left parotid gland along with C6 vertebral body haemangioma.
PMID- 26435997
TI - Primary Squamous Cell Carcinoma of Submandibular Salivary Gland with Sialo
Cutaneous Fistula: A Rare Case Report.
AB - Malignant tumours of the submandibular salivary glands are rare entities. Most
common malignant tumour of submandibular gland is mucoepidermoid carcinoma.
Histological finding of squamous cell carcinoma is very rare in submandibular
salivary gland. Metastasis from distant primary squamous malignancy, direct
invasion from cutaneous or mucosal squamous carcinoma, squamous component of
mucoepidermoid carcinoma or primary squamous cell carcinoma of salivary origin
are some of the possible causes. Of these, the latter is distinctly uncommon.
Primary squamous malignancy is diagnosed only after ruling out other possible
explanations. A positive mucin stain in the tumour or synchronous/ metachronous
squamous carcinoma elsewhere excludes the diagnosis of a primary carcinoma.
Primary squamous carcinoma is seen most commonly in parotid gland and rarely in
submandibular gland. We present a case of primary squamous cell carcinoma of
right submandibular salivary gland in a 45-year old-man. This case is presented
for the rare entity of primary squamous cell carcinoma in submandibular salivary
gland.
PMID- 26435998
TI - Marjolin's Ulcer in a Post Burn Scar of the Hand.
AB - Marjolin's ulcer arising from a post burn scar is rare. Here, we present a case
of an elderly male with a Marjolin's ulcer of the hand arising from a post burn
scar sustained two decades ago. The patient was not willing for an amputation, so
he was managed with a spit skin graft after explaining the possibility of
recurrence.
PMID- 26435999
TI - Membrane Sweeping for Vaginal Birth after Caesarean Section and its Outcome -A
Comparative Study.
AB - INTRODUCTION: Sweeping of membrane is a method of induction of labour. This is
used to avoid prolonged labour. However, there is paucity of data about the use
of this method for induction of labour and reducing prolonged labour in pregnancy
with previous caesarean section. This study is an effort to find the effect of
membrane sweeping in previous caesarean section. OBJECTIVE: To initiate labour in
previous LSCS patients by membrane sweeping and maternal outcome. STUDY SETTING:
This prospective randomised control study was conducted in Mahatma Gandhi Medical
College and Research Institute, Puducherry between January 2011 to June 2012.
MATERIALS AND METHODS: Seventy five women were randomly assigned to membrane
sweeping and seventy five to control. In study group serial membrane sweeping was
done once weekly from 39 weeks of gestation until the onset of labour up to
41weeks of gestation. In control group, no intervention up to 41 weeks of
gestation. All the cases were monitored by biophysical profile. OUTCOME MEASURES:
The primary outcomes measured were number of patients who had onset of labour.
The secondary outcome included the successful vaginal delivery, number of
membrane sweeping to initiate labour, sweeping to delivery interval and amount of
oxytocin required. RESULTS: The onset of labour in study group was 61.3% similar
in control group 64% with p 0.736. The mean interval from sweeping to labour
onset was 50.15+/-8 hours. The rate of VBAC was 17.3% in study group in compared
to 18.7% in control group and LSCS was 82.7% in study group in compared to 81.3%
in control group respectively. The mean gestation age at delivery 40+/-0.56 weeks
for study group compared with 39.92+/-0.55 weeks for control group. CONCLUSION:
Although membrane sweeping is an easy way of inducing labour, present study
failed to demonstrate its beneficial effect on obstetrical outcome.
PMID- 26436000
TI - Shoulder Tip Pain After Cesarean Section.
AB - AIM: The aim of this study was to investigate the frequency of postoperative
shoulder tip pain (STP) after cesarean section and compare spinal and general
anaesthesia with respect to STP. MATERIALS AND METHODS: Three hundred patients
who underwent cesarean section were randomly assigned to either spinal
anaesthesia group (Group SA, n=143) or general anaesthesia group (Group GA,
n=157). Postoperative STP was assessed at 8 hours and 24 hours after operation by
Visual Analogue Scale of Pain (VAS). RESULTS: There were no statistically
significant difference between the groups in terms of demographic data, operative
findings, and clinical outcomes. The overall incidence of STP in study population
was 35.7%. The incidence of STP in group SA (26.6%) was lower than that in group
GA (43.9%)(p=0.005). Moreover VAS scores for STP at 6 hours and 24 hours were
significantly lower in Group SA (p=0.001 and p<0.001, respectively). CONCLUSION:
Shoulder tip pain is a common complaint after cesarean section, which is more
prevalent in general anaesthesia.
PMID- 26436001
TI - Successful Outcome of Twin Gestation with Partial Mole and Co-Existing Live
Fetus: A Case Report.
AB - Sad fetus syndrome comprising of a live twin gestation with a hydatidiform mole
is a rare entity. The condition is even rarer when the co-existing live fetus is
associated with a partial mole than a complete mole. We report the case of a 24
year-old G2P1L1 at 28 weeks gestation who presented to our casualty in the second
stage of labour. She had a previous ultrasound scan at 13 weeks which showed a
live fetus with a focal area of multicystic placenta. She delivered an alive
preterm male fetus weighing 1.32 kg vaginally. Following expulsion of normal
placenta of the live fetus, partial mole was expelled. The fetus was admitted to
neonatal ICU and discharged after two weeks. Soon after delivery, beta-hCG (human
chorionic gonadotropin) was 1,21,993 mIU/ml which decreased to 30mIU/ml within
two weeks. The patient was discharged with advice of regular follow up of beta
hCG reports.
PMID- 26436002
TI - Proboscis Lateralis : A Rare Bilateral Case in Association with
Holoprosencephaly.
AB - Proboscis lateralis is a very rare congenital craniofacial malformation
characterized by a trunk like tubular appendage arising commonly from roof of the
orbit near medial canthus. It may be seen as an isolated defect with sporadic
occurrence or it may be associated with a spectrum of anomalies. It is usually
unilateral and very few bilateral cases of proboscis lateralis have been reported
in the literature worldwide. Alobar holoprosencephaly is commonly associated with
a single central proboscis and cyclopia. Here we report an unusual case of a
bilateral proboscis lateralis seen in association with holoprosencephaly.
PMID- 26436003
TI - Distinguishing Myasthenia Exacerbation from Severe Preeclampsia: A Diagnostic and
Therapeutic Challenge.
AB - Myasthenia gravis is an acquired, autoimmune neuromuscular disorder characterized
by voluntary muscle weakness. Pregnant patients may have disease exacerbation,
respiratory failure, crisis, adverse drug reaction, surprisingly enough remission
at any trimester or postnatal period. Concurrence of myasthenia gravis with
severe preeclampsia is a dreadful condition raising diagnostic and management
issues. We hereby discuss a case of myasthenic woman who developed severe
preeclampsia during pregnancy and presented in last trimester with clinical
features mimicking signs of impending eclampsia. Keeping in mind the history of
myasthenia gravis, urgent neurology review taken and diagnosis of myasthenic
exacerbation was entertained. She responded well to injection neostigmine and in
this way inadvertent use of magnesium sulphate was avoided.
PMID- 26436004
TI - Primary Peritoneal Hydatid Cyst Presenting as Ovarian Cyst Torsion: A Rare Case
Report.
AB - Hydatid cyst disease is a zoonotic disease caused by Echinococcus granulosus,
E.multilocularis or E.Vogli. The most common primary site is liver (75%) followed
by lungs (5-15%) and other organs constitute 10-20%. Peritoneal hydatid cysts are
very rare especially primary peritoneal hydatid. Secondary peritoneal hydatid
cysts are relatively common, which usually occurs due to rupture of primary
hepatic hydatid cyst. We present a rare case of large primary peritoneal hydatid
cyst misdiagnosed as torsion of ovarian cyst that underwent Laparotomy with cyst
excision and postoperative Albendazole therapy.
PMID- 26436005
TI - Catamenial Pain in Umbilical Hernia with Spontaneous Reduction: An Unusual
Presentation of a Rare Entity.
AB - Spontaneous umbilical endometriosis occurring in absence of any previous
abdominal or uterine surgery is extremely atypical. Its association with
umbilical hernia is very rare and hernia getting spontaneously resolved has not
been reported in literature so far. Here we report a case of a patient with
spontaneous umbilical endometriosis associated with umbilical hernia which led to
spontaneous hernia reduction. This was also associated with multiple uterine
fibromyoma and bilateral ovarian endometrioma which were simultaneously treated
by total abdominal hysterectomy with bilateral salpingo-oopherectomy along with
surgical excision of the endometriotic tissue and repair of the abdominal wall
defect. To the best of our knowledge, this is the first described case of
spontaneous umbilical hernia reduction due to development of endometriosis.
PMID- 26436006
TI - Comment on "Is It Safe to Provide Abortion Pills Over The Counter? A Study on
Outcome Following Self-Medication with Abortion Pills".
PMID- 26436007
TI - High Incidence of Stress Fractures in Military Cadets During Training: A Point of
Concern.
AB - INTRODUCTION: Stress fractures occur due to repetitive cumulative micro trauma on
the bone over a period of time. Stress fractures in military cadets is a rising
cause of concern. It increases morbidity, long periods of absence from training
and economic losses. AIM: The purpose of this prospective study was to determine
the incidence and distribution of stress fracture (SFs) in Border Security Forces
(BSF) cadets in Bangalore during their basic training tenure. MATERIALS AND
METHODS: A detailed analysis of history and physical assessment was performed of
those presenting with symptoms of pain, swelling or deformity. These cadets then
underwent radiographic imaging for the evaluation of symptoms. All cadets with
clinical and radiological diagnosis of SFs were appropriately managed and
followed up every two weeks till the time of union. RESULTS: Three hundred BSF
candidates had clinical and radiological signs of SF with an overall incidence
rate of 15%. The average age of the patients with SFs was 23 years (range 20-26).
The incidence of SFs was highest during their physical training exercises and
reached maximum at 12 weeks of the training schedule. Overall, the most common
sites of bone injuries were the tibia (87.66%), fibula (7.8%), and metatarsals
(2%). There were 5 femur fractures including one bilateral femur(1.67%) and two
neck of femur (0.67%). Three tibia, three femur shaft and two neck femur
fractures were operated and rest treated conservatively. All fractures healed in
an average period of seven weeks. All cadets returned to their full activity in
an average period of nine weeks. CONCLUSION: The study provides evidence that SF
among BSF cadets occur frequently during their training period with undoubtedly
high incidence rate which is probably underrated in Indian setting. To prevent
stress fractures, modifiable causes and risk factors must be identified and a
proactive approach which can help the cadets withstand intense physical activity
should be adopted.
PMID- 26436009
TI - Role of Arthroscopy in the Treatment of Osteoarthritis of Knee.
AB - BACKGROUND: A variety of procedures have been described for treatment of the
osteoarthritic knee. Comprehensive Arthroscopic treatment regime has definite
role in treating patients with knee Osteoarthritis. AIM: To evaluate the role of
arthroscopy in functional and subjective outcomes of patient with moderate to
severe osteoarthritis of knee. MATERIALS AND METHODS: Between October 2011 to
September 2013, 30 patients were treated with an arthroscopic regimen. Patients
with primary osteoarthritis who fulfilled clinical and radiographic
classification criteria of American College of Rheumatology for osteoarthritis
were included. All patients were followed for 18 months. All patients were
subjected to comprehensive arthroscopic treatment. RESULTS: Overall, mean age was
59 years, with 17 females and 13 males. According to Kellgren Lawrence scale, 17
patients had grade 2 osteoarthritis, 10 had grade 3 osteoarthritis and 3 patients
had grade 4. The average preoperative Lysholm score was 38.8. According to
Outerbridge grading of chondral surface lesions, 14 patients were in grade-1, 5
in grade-2, 8 in grade-3 and 3 patients were in grade-4. The average 18 months
postoperative Lysholm score was 83.3 (range 60- 96). 73.33% patients showed good/
excellent outcome. 80% of patients with chondral and meniscal lesions showed
excellent/good outcome. CONCLUSION: This arthroscopic treatment regimen can
improve function and activity levels in patients with moderate to severe
osteoarthritis. Patients with meniscal and chondral pathology will be benefited
more by arthroscopic treatment.
PMID- 26436008
TI - Serum Osteocalcin as a Diagnostic Biomarker for Primary Osteoporosis in Women.
AB - INTRODUCTION: Osteoporosis, a major health problem in elderly population,
especially in post-menopausal females, is diagnosed basically on clinical
suspicion and bone mineral density measurement. Dual energy x-ray absorptiometry
(DEXA) scan though a gold standard of diagnosis becomes unfit for screening
purpose due to its prohibitive cost, unportability and lack of availability of
machine. AIM: To assess the diagnostic potential of serum osteocalcin levels in
primary osteoporosis. MATERIALS AND METHODS: In a case-control study, 82 post
menopausal females, between 40-70 years, were subjected to measurements of bone
mineral density and serum osteocalcin levels. Based on the results of DEXA scan
they were divided into two: a) Control group and B) Case group. Case group was
further subdivided as Osteopenia and Osteoporosis depending on their t-scores.
Correlation between different BMD grades and the levels of serum osteocalcin were
analysed statistically. RESULTS: A negative correlation was found between serum
osteocalcin levels and BMD grading. Significant association of age and years
since menopause (YSM) was found with serum osteocalcin levels and BMD. No
association of BMI and serum osteocalcin was observed with BMD. Statistically
significant difference between values of serum osteocalcin in postmenopausal non
osteoporotic women, post-menopausal women with low bone mass (osteopenia) and
post-menopausal women with osteoporosis were seen. CONCLUSION: Serum osteocalcin
level measurement can be used for screening purpose in post-menopausal patients.
Subjects can be further assessed by DEXA scan to, if indicated.
PMID- 26436010
TI - Clinical and Genetic Analysis of Fibrodysplasia Ossificans Progressiva: A Case
Report and Literature Review.
AB - Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder
characterized by congenital malformation of the great toes and disabling
heterotopic ossification in specific anatomic locations with a world wide
prevalence of 1 in 2 million population. Nearly 90% of patients with FOP are
misdiagnosed and mismanaged. We present a case of a four-year-old boy brought by
his parents with the complaints of stiffness of right shoulder, neck and multiple
swellings over the upper back noted over the past 4 months. On examination
bilateral symmetrical hallux valgus with microdactyly of great toes and multiple
bony hard swellings on both the scapulae were noted. Skeletal survey revealed all
the classical features of FOP. Mutation of the ACVR1gene on genetic analysis
confirmed the diagnosis of FOP. Invasive surgical procedures including biopsy and
manipulations for stiff joints were avoided as they strikingly end up in rapid
progression of FOP. Congenital hallux valgus with short great toe in a child
should be considered as an early diagnostic tool for FOP even before the onset of
mass lesions. Genetic analysis for mutation of ACVR1gene is confirmatory.
Prevention of injury, medical management of acute painful flare-ups and
rehabilitation are the mainstay of treatment.
PMID- 26436011
TI - Six Sesamoid Bones on Both Feet: Report of a Rare Case.
AB - There is a variation of the total number of distinct bones in the human in the
literature. This difference is mainly caused by the variable existence of
sesamoid bones. Sesamoid bones at the first MTP are seen regularly. In contrast
additional sesamoid bones at the second to fifth MTP are rare. We report a case
of additional sesamoid bones at every metatarsophalangeal joint (MTP) of both
feet. A 22-year-old female Caucasian presented with weight-dependent pain of the
second MTP of the left foot. In the radiographs of both feet additional sesamoid
bones at every MTP could be seen. This case reports a very rare variation in
human anatomy. A similar case has not been displayed to the academic society and
therefore should be acknowledged.
PMID- 26436012
TI - The Incidence of Allergic Disorders in First Degree Relatives of Neonates with
Transient Tachypnea of Neonate.
AB - BACKGROUND: The role of maternal allergic disorders to increase the risk of
Transient Tachypnea of Neonate (TTN) in neonates remained unclear. We determined
the incidence of allergic disorders in first degree relatives of neonates
suffered from TTN to clear role of these allergic disorders to predispose TTN in
neonates. MATERIALS AND METHODS: In a cross-sectional study carried out at
Fatemieh hospital between September 2010 and September 2011, all consecutive
neonates with the diagnosis of TTN were included into the study. Those neonates
were not treated after 5 days of hospitalization were excluded. Baseline
information with regard to the history of allergic diseases among first degree
relatives of neonates were charted from family members using a structured
questionnaire at enrolment by interviewing and examination if required. RESULTS:
The two groups were matched for baseline data including neonate gender, birth
weight, and type of delivery. In the TTN group, one of first degree relatives
(2.9%) suffered from bronchial asthma and two of them (5.7) had atopic
dermatitis. In total, allergic diseases was revealed in 8.6% of first degree
relatives of neonates with TTN. Besides, none of the first degree relatives of
neonates in healthy neonates group experienced bronchial asthma or atopic
dermatitis. Allergic rhinitis was not also found in the relatives of the two
study neonates groups. Comparing incidence of allergic diseases in first degree
relatives of neonates in TTN and healthy groups showed no significant difference
(8.6% in TTN group versus 0.0% in healthy group, p = 0.076). CONCLUSION: Our
study showed that the incidence of allergic disorders in first degree relatives
of neonates suffered from TTN is higher than healthy newborns, but these
differences are not statistically significant.
PMID- 26436013
TI - Clinical and Laboratory Potential Predictors of Blood Culture Positivity in Under
Five Children with Clinically Severe Pneumonia - Khartoum -Sudan.
AB - BACKGROUND: Blood culture is necessary for appropriate management of clinically
severe pneumonia in children under five years of age. However, in limited
resource countries it might be unduly costly and waste of valuable time because
of the high negative culture rate. OBJECTIVES: This study aims to identify
clinical and laboratory parameters that potentially predict a positive blood
culture in cases of severe pneumonia. MATERIALS AND METHODS: A hospital based
study, enrolled 189 cases satisfying the WHO definition of severe pneumonia. Age,
gender, clinical history, physical examination, temperature, complete blood
count, C-reactive protein, blood culture and Chest X Ray for all the patients
were recorded. RESULTS: Forty one patients had positive blood culture giving a
prevalence of 21.7%. All variables were used in a dichotomous manner. White Blood
Count (WBC) more than 20 000, very high C-reactive protein (C-RP >=8mg/L) and
Temperature more than 40(o)C, had a positive predictive value of 46.1%, 44.3% and
40.0% respectively for a positive culture as well as a Negative Predictive Value
of 91.1%, 91.6% and 91.7% respectively. The WBC more than 20 000 and temperature
above 40(o)C had a significant association with a positive blood culture. Their
adjusted Odds Ratios were 3.9 (95% CI: 1.4-10.90) and 3.1 (95% CI: 1.2-8.4)
respectively. This was not the case for C-RP (Odds Ratio=2.2, 95% CI: 0.7-2.2) or
positive Chest X Ray (Odds Ratio=1.5, 95% CI: 0.6-3.6). CONCLUSION AND
RECOMMENDATION: Temperature of more than 40(o)C, Very high C-RP and WBC of more
than 20 000 are good indicators of a potential positive blood culture. It is
therefore recommended that further research be undertaken to refine these
predictors as screening tools before resorting to blood culture. It is also
recommended that antibiotic treatment may be initiated on the basis of the high
temperature and WBC, while waiting for the culture results.
PMID- 26436014
TI - Modified Computed Tomography Severity Index for Evaluation of Acute Pancreatitis
and its Correlation with Clinical Outcome: A Tertiary Care Hospital Based
Observational Study.
AB - BACKGROUND: Acute Pancreatitis is a very common condition leading to the
emergency visits in both developed and developing countries. Computed Tomography
plays a pivotal role in the diagnosis and subsequent management of pancreatitis.
The modified CT severity index includes a simplified assessment of pancreatic
inflammation and necrosis as well as an assessment of extra pancreatic
complications. AIM: To study role of modified computed tomography severity index
in evaluation of acute pancreatitis and its correlation with clinical outcome.
MATERIALS AND METHODS: This was a hospital based prospective correlative study
done on patients of all age groups referred to the Department of Radio diagnosis
from the various indoor and outdoor departments of the hospital, with
clinical/Laboratory/ultrasonography findings suggestive of acute pancreatitis.
The severity of pancreatitis was scored using Modified CT severity index & CT
severity index and classified into mild, moderate and severe categories. Total of
50 patients of acute pancreatitis presenting to the emergency department of our
hospital were included in the study. Clinical outcome parameters for correlation
collected from respective referral departments included, the length of hospital
stay (in days), need for surgical intervention, need for percutaneous
intervention (aspiration and drainage), evidence of infection in any organ system
(combination of a fever > 100 degrees F and elevated WBC >15,000/ mm(3)),
evidence of organ failure (PaO2 < 60 mm Hg or need of ventilation, systolic BP of
< 90 mm Hg, serum creatinine of >300MUmoles/L or urine output of < 500 ml / 24 h)
and death. RESULTS: The age of the patients in the study group was in the range
of 17 to 80 years. Maximum patients were in the age group 40-50 years (42.0%).
The mean age was 42.32 years. Out of 50 cases, 33 (66%) were male and 17 (34%)
were females with a male to female ratio of 2:1. Cholelithiasis was found to be
most common aetiological factor for acute pancreatitis in 40% cases. Alcoholic
pancreatitis was seen in 36% of cases. Together cholelithiasis and alcoholism
accounted for 76% of cases. Pleural effusion was the most common extra-pancreatic
complication, 28 patients (56%), followed by ascites. Majority of patients were
categorized as severe pancreatitis (44%). 38% patients were grouped into moderate
pancreatitis and 18% were categorized in mild pancreatitis. The outcome
parameters in terms of length of hospital stay, need of intervention, development
of infection, and development of organ failure were more in patients with higher
modified CT severity index. CONCLUSION: In conclusion CECT was found to be an
excellent imaging modality for diagnosis, establishing the extent of disease
process and in grading its severity. The Modified CT Severity Index is a simpler
scoring tool and more accurate than the Balthazar CT Severity Index. In this
study, it had a stronger statistical correlation with the clinical outcome, be it
the length of hospital stay, development of infection, occurrence of organ
failure and overall mortality. It could also predict the need for interventional
procedures.
PMID- 26436015
TI - Primary Hydatid Cyst of the Diaphragm Mimicking Diaphragmatic Tumour: A Case
Report.
AB - Echinococcus commonly affects the liver and the lung, but several organs can be
affected by this disease. The isolated primary diaphragmatic hydatid cyst, not
associated with liver or lung, is very rare. We report a case of hydatid cyst in
a 55-year-old male, located in the abdominal side of the left hemidiaphragm which
mimicked a hypovascular diaphragmatic tumour and exophytic splenic cyst. In our
case the diagnosis was confirmed only with histopathological examination done
after surgical excision of the cyst. The aim of this work lies in the fact that
knowledge of this clinical entity especially in endemic areas as in India will
enable radiologists to guide the clinicians in proper diagnosis and adequate pre
operative planning.
PMID- 26436016
TI - H' Shaped Bilobate Placental Partition: A Rare Placenta Variation.
AB - Anomalies of placental growth with respect to its shape have been associated with
adverse pregnancy outcomes. A very rare form of 'H' bilobate placental partition
was observed in a 31-year-old woman presenting at 24 weeks of gestation. This
observation was made during a routine obstetrics scan. Sonographic features
showed that it was a non-fibroid partition. The placenta featured anterior and
posterior portions separated by a large middle, vertical portion. The placenta
was antero-posterior semi-circumferential in shape, measuring approximately 16.70
cm in length and 12.48 cm at shorter chorionic plate (minor axis). The middle,
vertical part of the placenta partitioned the uterine cavity into two, creating
the impression of two separate gestational sacs. The fetus was located in one of
these. The patient was eventually delivered through caesarean section at
gestational age (GA) of 36 weeks 6 days. The baby had a low birth weight of 1.70
kg. The early detection of this placental anomaly underlines the importance of
ultrasonography in obstetrics.
PMID- 26436017
TI - Spontaneous Partial Vanishing Cytomegalovirus Pseudotumour of Colon in an
Immunocompetent Patient.
AB - Cytomegalovirus (CMV) pseudotumour of the gastrointestinal tract, is a rare
benign entity which is treated with antiviral medications and known to resolve
spontaneously in a few cases. This is a case report of a 58-year-old man who
presented with right lower quadrant abdominal pain. Contrast enhanced
computerized tomography of abdomen and pelvis showed apple core lesion involving
proximal transverse colon, ceacum, ascending colon, ileoceacal valve and terminal
ileum. Synchronous carcinoma of colon was suspected. At laparotomy, there was
growth palpable only in the proximal transverse colon. Histological findings of
biopsy specimen revealed CMV pseudotumour. CMV pseudo tumour should be included
in the differential diagnosis of apple core lesions of the colon even in
immunocompetent adults. Endoscopy and biopsy are strongly recommended before
surgery in colonic mass lesions to make a definitive diagnosis and to avoid
unnecessary surgery.
PMID- 26436018
TI - Hirayama Disease: Escaping From the Quotidian Imaging.
AB - Hirayama disease is a rare type of neurological disease commonly manifesting as
brachial monomelic amyotrophy in young males of Asian origin, easily understood
as juvenile non-progressive cervical amyotrophy. The first case was reported by
Hirayama in 1959. The pathogenesis is attributed towards chronic compression of
cervical spinal cord during flexion movements of neck in cases where there is
detachment of posterior dura mater. This chronic event, invariably leads to
features of cord atrophy along with other MRI features. We report a case of 21
year-old male who presented with atrophy of distal muscles of his right hand and
was sent for MRI of cervical spine which revealed prominent posterior epidural
venous plexus without significant cord atrophy. Clinico-radiologic profile of the
patient leads toward the diagnosis of Hirayama disease which was considered as
borderline because of asymmetrical cord atrophy which is a not a routine imaging
feature of the entity.
PMID- 26436019
TI - Osteopetrosis - Classic Imaging Findings in the Spine.
PMID- 26436020
TI - Role of Advanced Diagnostic Imaging in Intracranial Tuberculoma: MR Spectroscopy.
PMID- 26436021
TI - A Comparison of Efficacy of Segmental Epidural Block versus Spinal Anaesthesia
for Percutaneous Nephrolithotomy.
AB - INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is done under general
anaesthesia in most of the centres. Associated complications and cost are higher
for general anaesthesia than for regional anaesthesia. Present study is designed
to compare the efficacy of epidural block versus spinal anaesthesia with regards
to intraoperative mean arterial pressure, heart rate, postoperative pain
intensity, analgesic requirement, Postoperative complications and patient
satisfaction in patients undergoing PCNL. MATERIALS AND METHODS: After taking
Ethical Committee clearance, patients were randomly allocated into 2 groups using
table of randomization (n= 40 each) Group E- Epidural block, Group S- Spinal
block. Various parameters like intraoperative mean arterial pressure, heart rate,
postoperative pain intensity, analgesic requirement, postoperative complications
and patient satisfaction were studied in these groups. STATISTICAL ANALYSIS:
Quantitative data was analysed using unpaired t-test and qualitative data was
analysed using chi-square test. RESULTS: Twenty four times in Epidural as
compared to fifteen times in spinal anaesthesia two or more attempts required.
Mean time (min) required to achieve the block of anaesthesia in group E and group
S was 15.45+/-2.8 and 8.52+/-2.62 min respectively. Mean arterial pressure (MAP)
at 5 min, 10 min and 15 min were significantly lower in spinal group as compared
to epidural group. After 30 minutes, differences were not significant but still
MAP was lower in spinal group. After 30 minutes difference in heart rate between
two groups was statistically significant and higher rate recorded in spinal group
till the end of 3 hours. Postoperative VAS score was significantly higher in
spinal group and 4 hours onwards difference was highly significant. Postoperative
Nausea Vomiting (PONV) Score was significantly higher in spinal group as compared
to epidural group. CONCLUSION: For PCNL, segmental epidural block is better than
spinal anaesthesia in terms of haemodynamic stability, postoperative analgesia,
patient satisfaction and reduced incidence of PONV. Epidural anaesthesia is
difficult to execute and takes longer time to act as compared to spinal block
which limits its use.
PMID- 26436022
TI - A Pilot Study of Cerebral and Hemodynamic Changes During Sedation with Low Dose
of Thiopental Sodium or Propofol in Patients with Acute Brain Injury.
AB - BACKGROUND: One of the most important therapeutic maneuvers in head injury
patients is to maintain Intracranial Pressure (ICP) and Cerebral Perfusion
Pressure (CPP) within normal levels. AIMS: To compare the effects of low dose of
thiopental sodium and propofol on reducing ICP and CPP in patients with head
injury that scheduled for neurosurgical interventions. SETTINGS AND DESIGN: Using
a randomized, crossover pilot study, we enrolled patients with head injury that
scheduled for neurosurgical interventions admitted to ICU unit of a teaching
hospital during 2010 to 2011. MATERIALS AND METHODS: In this pilot study,
patients randomized into two equal groups. The first group received bolus
injection of thiopental sodium 2 mg/kg and a maintenance dose of 2 mg/kg/h and
the second group was given a bolus dose of propofol 0.5 mg/kg followed by
propofol infusion 20 MUg/kg/min. All of patients were given dexamethasone 8 mg at
time of catheter insertion. ICP measurement catheter was inserted for each
patient and ICP, CPP, SPO2 and MAP were recorded hourly for a period of 6 hours.
RESULTS: There was no significant difference in sex and age between the two study
groups (p>0.05). The mean ICP, CPP, SPO2 and arterial blood pressure were found
to be similar with no significant difference between both groups (p>0.05).
CONCLUSION: Both propofol and thiopental sodium were equally effective in
monitoring and maintaining CPP and MAP and eventually an ideal SPO2.
PMID- 26436023
TI - Naphthalene Poisoning following Ingestion of Mothballs: A Case Report.
AB - Naphthalene is a widely used industrial and household chemical in the form of
mothballs. But it has rarely been an agent of poisoning worldwide. We describe a
case of ingestional naphthalene poisoning with a good outcome after proper
management. A 29-year-old girl ingested 8 mothballs, and presented two days later
with haemolysis and methaemoglobinaemia. She was given intravenous methylene
blue, N-acetylcysteine and ascorbic acid, besides supportive treatment. Renal
replacement therapy in the form of SLED of 8 hours was done on a daily basis. She
was discharged after ten days on twice a week outpatient follow-up haemodialysis.
PMID- 26436024
TI - TIVA-A Promising Approach to Anaesthetic Management of Montgomery T-tube
Insertion.
AB - One of the treatment modalities for tracheal stenosis is tracheal dilatation and
stenting using silicone Montgomery T-tube. Various techniques have been reported
for this procedure. For safe anaesthetic management, anaesthesiologist must be
aware of the surgical procedure, limitations of T-tube, likelihood of compromised
airway besides the inherent problems of sharing the airway with surgeons. Total
intravenous anaesthesia (TIVA) is a technique which has become very popular and
possible now a days for various surgical procedures owing to its advantages. The
anaesthetic technique should be based on the provider's experience and severity
of tracheal stenosis. We present here the anaesthetic management using TIVA
technique with propofol and atracurium for the insertion of Montgomery T-tube in
a case of post intubation tracheal stenosis.
PMID- 26436025
TI - Is 'Pure' Dhat Syndrome a Stable Diagnostic Entity? A Naturalistic Long Term
Follow Up Study from a Tertiary Care Centre.
AB - BACKGROUND: Very little is known about the long term diagnostic stability of Dhat
(semen loss) syndrome owing to a dearth of follow up studies on this condition.
AIM: The aim of the study was to assess the diagnostic stability and naturalistic
long term outcomes in a group of pure Dhat syndrome cases. MATERIALS AND METHODS:
The study was carried out in the outpatient psychiatry department of a tertiary
care hospital in South India, using a retrospective cohort design. Forty one
cases of 'pure' Dhat syndrome (with no other concurrent diagnosis) were selected
by a chart review of patients attending the outpatient Psychiatry department. Out
of this initial cohort, follow up interviews were held for 36 patients. Direct
clinical interviews were held with all participants to assess change in
diagnosis. Those who no longer qualified for Dhat syndrome were interviewed with
the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to
generate other diagnoses. For analysis, the patients were divided into two groups
- those who positively endorsed symptoms of Dhat syndrome at follow up (DSP
group) and those who no longer did (DSN group). These groups were compared using
chi-square test for categorical variables and student t-test for continuous
variables to look for significant differences. Frequencies and percentages were
used to depict socio-demographic data and the follow up diagnoses. STATISTICAL
ANALYSIS: Data was analysed using SPSS for Windows, Version 16.0 (Chicago, SPSS
Inc.). RESULTS: The mean duration of follow up was 6+/-3.5 years. Nearly two
thirds of the sample no longer fulfilled criteria for Dhat syndrome in follow up.
The most common revisional diagnosis in these patients was somatoform disorders.
Age, marital status and literacy distinguished the two groups. About a quarter of
the sample (26.07%) was in complete remission. CONCLUSION: Even the purest
variety of Dhat syndrome is not a stable diagnosis in the majority of patients.
The condition may be better conceptualized as a subtype of somatoform disorder
with culturally determined explanation for somatic symptoms. Clinicians should
look at explanations of semen loss as fluid cultural idioms of distress rather
than as a standalone diagnostic entity.
PMID- 26436026
TI - A 16-Year-old Boy with Combined Volatile and Alcohol Dependence: A Case Report.
AB - Substance abuse has been defined as the use of chemical substances for non
medical purposes in order to achieve alterations in psychological functioning.
The substances commonly abused in India include nicotine, alcohol, cannabis and
opioids. However, the use of solvents and propellants is also on the rise as
these are inexpensive, legally available household, industrial, office and
automobile products; which are more commonly available to children and
adolescents. We hereby describe a 16-year-old boy with combined volatile and
alcohol abuse; who presented with increasing ataxia, visual and hearing
disturbances.
PMID- 26436027
TI - A Hospital-based Study to Determine Causes of Diffuse Hair Loss in Women.
AB - BACKGROUND: Diffuse hair loss is a common complaint encountered by dermatologists
in their daily clinical practice. Hair loss in women is a distressing condition.
Various underlying factors individually or in combination contribute to the
pathogenesis. OBJECTIVES: To determine causes of diffuse hair loss in women and
to find the association between probable causes and relevant laboratory
parameters, wherever applicable. MATERIALS AND METHODS: One hundred and eighty
women with diffuse hair loss were included in the study. Detailed history and
clinical examination including hair pull test and hair microscopy were done in
all study subjects. Specific laboratory investigations for determining iron
deficiency anaemia, thyroid dysfunction and parasitic infestation were done.
RESULTS: Among 180 patients, 116 (64.44%) had telogen effluvium, 28 (15.55%) had
CTE, 21 (11.66%) had FPHL and 1 (0.55%) had AE. Fourteen patients (7.77%) had
more than one aetiological diagnosis of diffuse hair loss. TE was the commonest
type of diffuse hair loss. Incidence of TE and FPHL were highest in the age group
of 21-30 years, whereas CTE in 30-40 years. Psychological stress and iron
deficiency anaemia were the most common underlying aetiological factors for TE,
which is statistically significant (p<0.05). Out of 130 patients with TE, more
than one aetiological factor was recorded in 10 cases whereas in 32 cases
probable aetiological factors could not be elicited from history. Most cases of
CTE were idiopathic. No significant relationship was observed between CTE,
haemoglobin level and serum ferritin level. Out of 35 patients with FPHL, low
haemoglobin level was observed in 6/20 (30%) and low serum ferritin level in
14/17 (82.35%). CONCLUSION: Diffuse hair loss is a multifactorial condition. A
detailed history, thorough clinical examination and appropriate investigations
help to identify the causative factors and treat them accordingly.
PMID- 26436028
TI - Pattern of Cancers Treated with Radiotherapy in Uduth Sokoto: A New Center
Experience.
AB - BACKGROUND: Cancer is a leading public health problem worldwide. In many
developing countries, cancer tends to present in predominantly advanced stages,
to a certain extent due to lack of comprehensive screening and poor access to
efficient management. This study was carried out to describe the pattern of
cancers managed in the Department of Radiotherapy and Oncology in Usmanu
Danfodiyo University Teaching Hospital Sokoto, North-western Nigeria. MATERIALS
AND METHODS: This was a cross-sectional descriptive study involving patients with
malignancies that attended the new Oncology Department of the Usman Danfodiyo
University Teaching Hospital Sokoto, North-West Nigeria for the period of one
year (June 2013 - May 2014). The data was analyzed using SPSS (versions 20).
RESULT: A total of 210 patients with complete records met the criteria for the
study. Majority 162 (77.1%) were females with a mean age of 45.68+/-12.4 years.
The male patients were 48 (22.9%) with mean age 46.27+/-16.5. The spectrum of
malignant lesions observed were cancer of the cervix 77 (36.67%), breast cancer
74 (35.24%), nasopharyngeal cancer 20 (9.52%), cancer of the larynx 18 (8.57%)
and rectal cancer 14 (6.67%). Late presentation was most common with 6 (3%), 101
(49.8%) and 58 (28.6%) patients presenting at stage I, III and IV, respectively.
CONCLUSION: The study demonstrates that Cancer of the cervix is the leading
malignancy in the study population.
PMID- 26436029
TI - Oral Cancer Knowledge, Attitudes and Practices: A Survey of Undergraduate Medical
Students in Himachal Pradesh, India.
AB - BACKGROUND: Oral cancer is the sixth most common cancer among Indian males and
the third most common cancer among Indian females. Early detection of oral
cancers makes them more amenable to treatment and allows the greatest chance of
cure. Lack of awareness among the health care providers is the most significant
factor in delaying diagnosis and treatment of oral cancer. So the aim of the
study was to assess the knowledge, attitude and practices of oral cancer among
undergraduate medical students in Indira Gandhi Medical College, Shimla, India.
MATERIALS AND METHODS: A cross-sectional questionnaire study was conducted among
186 undergraduate medical students between the third to fifth years in Indira
Gandhi Medical College, Shimla. The questionnaire consisted of 15 questions, five
each on knowledge, attitudes and practices. The data were analysed by Statistical
Package for the Social Sciences version 16. Test used were t-test, Chi-square and
ANOVA. RESULTS: The response rate of the study was 96.5%. The mean knowledge
percent of the sample was good. Mean knowledge percent was higher in females than
males. Higher percentage of students in 5(th) year (internship) had excellent
knowledge. The knowledge and practices about risk factors was not satisfactory.
One hundred and twenty four (66.6%) of the subjects disagreed/strongly disagreed
that their knowledge regarding the prevention and detection of oral cancer is
current adequate. One hundred and seventy six and (94.6%) agreed/strongly agreed
that there is need for additional training/information regarding oral cancer.
CONCLUSION: It can be concluded that though the mean knowledge of the population
was good but the knowledge and practices about risk factors had to be reinforced
among these students so that they can help the patients in tobacco and alcohol
cessation and contribute in prevention of oral cancers.
PMID- 26436030
TI - PNET of the Abdominal Wall: A Rare Presentation.
AB - Primitive neuroectodermal tumours (PNETs) are a malignant group of neoplasms and
are neuroectodermal in origin. In most large series published to date, peripheral
primitive neuroectodermal tumours usually present in the second decade of life,
with a slight male preponderance. Those which occurs peripherally resemble soft
tissue sarcomas. Peripheral PNET is rare in presentation and of which only few
cases involving the soft tissues of the abdominal wall have been reported. We
present a case affecting a young female who presented to us with a progressively
enlarging swelling involving the anterior abdominal wall. She underwent wide
excision followed by adjuvant therapy based on final histopathology report.
PMID- 26436031
TI - Dermatofibrosarcoma Protuberans of Lumbar Region with Metastasis to Lung: A Rare
Presentation.
AB - Dermatofibrosarcoma protuberans (DFSP) is a cutaneous slow growing soft tissue
sarcoma associated with a high local recurrence rate. Common site of presentation
is trunk followed by proximal extremity and head and neck region. A case of
recurrent DFSP of left lumbar region with metastasis in lung in a 50-year-old
woman presented here. Absence of symptoms often leads to a delay in diagnosis.
DFSP is often mistaken for other skin conditions, particularly in its early
stages.
PMID- 26436032
TI - Radiotherapy-Induced Vitiligo in a Patient with Carcinoma Buccal Mucosa: A Case
Report.
AB - Vitiligo significantly affects self-esteem and deteriorates the quality of life
of affected persons. Radiotherapy has several early and late effects but it is
not known to induce vitiligo. This is a case report of a patient suffering from
carcinoma buccal mucosa that had developed vitiligo in the radiotherapy portal.
To the best of my knowledge this is a one of the first case reports of its kind
as this patient had no history of vitiligo but developed it soon after
radiotherapy. Since radiotherapy is an essential component of cancer management,
the radiation oncologist must be aware of this toxicity of radiotherapy. Choosing
the high energy of photon beam may reduce the risk of such toxicities.
PMID- 26436033
TI - Ectopic Male Breast Cancer: A Case Report.
AB - Carcinoma of male breast constitutes 1% of total breast malignancy. Carcinoma
arising from ectopic breast tissue in male is an extremely rare entity and can be
misdiagnosed. Ectopic breast tissue may be supernumerary or aberrant one. Despite
morphologic difference, ectopic breast tissue presents characteristics analogous
to orthoptic breast in terms of functional and pathologic degeneration. Most of
the ectopic breast tissue occurs in thoracic or abdominal portion of milk line.
If found in a location outside the milk line, it proves a diagnostic dilemma. We
are reporting a case of 60-year-old male who presented with a fixed mass of size
10cm*8cm, in right chest wall infraclavicular area of 6 months duration.
Histopathology of the mass revealed invasive duct carcinoma. He had no evidence
of malignant or occult primary lesion in the bilateral mammary glands. Due to the
paucity of the literature, incidence of ectopic male breast cancer and its
management is not well understood. There is high probability of misdiagnosis of
this disease. To the best of our knowledge this is the first described case of
ectopic male breast cancer in the chest wall, not along the milk line, which is
being reported here for documentation.
PMID- 26436034
TI - Changes in Capacity and Performance in Mobility Across Different Environmental
Settings in Children with Cerebral Palsy: An Exploratory Study.
AB - BACKGROUND: Children with cerebral palsy, although having similar diagnosis,
varies in their abilities & level of functioning within & across different
environmental context e.g. home, school or community setting. Capacity (what a
child can do in standardized, controlled environment) may or may not be the same
as performance (what a child actually does do in her/her daily environment).
MATERIALS AND METHODS: After getting approval from Institutional Ethic's
Committee (IEC), 63 children with cerebral palsy (4-16 year, mean 7.4 year with
SD 0.39) of all clinical types, Gross Motor Functional Classification System
(GMFCS) level I-V were examined for mobility using Gross Motor Functional Measure
88 (GMFM). Motor capacity was assessed in clinical setting by highest of 3 GMFM
items attained, i.e., crawling (44), walks with support (68) & walks without
support (70). Motor performance was measured by Functional Mobility Scale version
2. RESULT: On analysis of motor capacity 42.85% children were walking without
support, 15.87% were able to crawl & 26.98% were able walk with support in
clinical setting. Spearman's Correlation was done between GMFM item 70 with FMS 5
(home setting) to check correlation of capacity with performance & was found to
be significantly correlated (r=0.586, p=0.04). All three GMFM items were
correlated with FMS 5, 50, 500 & found positively correlated. For community
setting (FMS 500), 52.38% children were lifted by parents & only 6.34% were using
wheel chair mobility. A total of 21.87% patients were able to walk with or
without support & still lifted by parents in school or community setting.
CONCLUSION: Change in capacity and performance of mobility exists mainly in
school and community setting in studied population. Context should be given
importance to prioritize rehabilitation process.
PMID- 26436035
TI - Validity of Moyers Mixed Dentition Analysis and a New Proposed Regression
Equation as a Predictor of Width of Unerupted Canine and Premolars in Children.
AB - INTRODUCTION: The Moyer's mixed dentition analysis forms an essential part of
diagnostic procedures to determine adequacy of the space available for the
erupting permanent teeth. However, its reliability among different racial groups
has been questioned. OBJECTIVES: The objectives of this study were to test the
reliability of Moyer's method and to produce new regression equation for
Bangalore population for predicting the mesiodistal diameters of the unerupted
permanent canines and premolars. MATERIALS AND METHODS: Data was collected from
study models of 400 randomly selected Bangalore subjects aged 13 to 16 years with
fully erupted, intact dentitions and no significant malocclusion. The mesiodistal
widths of the incisors, canines and premolars of both arches were measured. This
data was then utilized to predict the mesiodistal widths of canines and premolars
and further compared with Moyer's table. CONCLUSION: It was found that 50% is
more applicable to boys and 75% to girls. The canine premolar segment in both
arches is statistically larger in men than in women (p<0.05). New regression
equation was formulated, the accuracy of which needs to be evaluated further in a
larger sample.
PMID- 26436036
TI - Invitro Anti-mycotic Activity of Hydro Alcoholic Extracts of Some Indian
Medicinal Plants against Fluconazole Resistant Candida albicans.
AB - BACKGROUND: Candidiasis is one of the most common opportunistic infections caused
by Candida albicans. Fluconazole is the drug of choice for prevention and
management of this condition. However, the emergence of fluconazole resistant
candidal strains has become a major concern. Many herbs like fenugreek, cinnamon,
papaya, oregano, garlic are rich in phytochemical constituents known to express
antimycotic activity. With the available information, the present research study
was carried out to assess the invitro anti-mycotic activity of hydro alcoholic
extracts of Trigonella foenum-graecum seeds, Cinnamomum verum bark and Carica
papaya leaves and seeds against fluconazole resistant Candida albicans. MATERIALS
AND METHODS: Hydro alcoholic extracts of Trigonella foenum-graecum (seeds),
Cinnamomum verum (bark), Carica papaya CO.2 strain (male and female leaves) and
Carica papaya CO.2 strain (seeds) were prepared by maceration. The anti-mycotic
activity of the prepared extracts against Candida albicans was assessed by agar
well diffusion method. Three independent experiments were performed in
triplicates and the mean and standard deviation were calculated. Minimum
inhibitory concentration was determined. RESULTS: The results of the present
study revealed that all the extracts exhibited anti-mycotic activity in a dose
dependent manner and minimum inhibitory concentration of all the extracts was
found to be 15.62 MUg/ml. CONCLUSION: The results of the present study shed light
on the fact that plant extracts could be used not only as an alternate drug for
management of fluconazole resistant candidiasis but also explored further for
oral cancer prevention as a therapeutic adjunct.
PMID- 26436037
TI - A Comparative Evaluation of the Amount of Fluoride Release and Re-Release after
Recharging from Aesthetic Restorative Materials: An in vitro Study.
AB - AIM: To measure the amount of fluoride released and re released after recharging
from various restorative materials: Conventional Glass Ionomer Cement (Fuji II),
Light Cure Resin Modified GIC (Fuji II LC), Giomer (Beautifil II), Compomer
(Dyract). MATERIALS AND METHODS: Fifteen cylindrical specimens were prepared from
each material. The specimens were immersed in 20 ml of deionized water. The
amount of released fluoride was measured during the 1(st) day, 7(th) day and on
the day15 by using specific fluoride electrode and an ion-analyser. After 15 days
each material was divided into three Sub Groups of five samples each. Sub Group A
served as control, Sub Group B was exposed to 2% NaF solution, Sub Group C to
1000ppm F toothpaste. The amount of fluoride re-released was measured during the
1(st) day, 7(th) day and on the day15 by using specific fluoride electrode and an
ion-analyser. The results were statistically analysed using analysis of variance
(one-way ANOVA) and Tukey Kramer multiple comparison tests (p<=0.05). RESULTS:
Independent of the observation time period of the study the Conventional GIC
released the highest amount of fluoride followed by RMGIC, Giomer and Compomer.
The initial burst effect was seen with GIC'S but not with Giomer and Compomer.
After topical fluoride application fluoride re release was highest in Sub Group B
and GIC had a greater recharging ability followed by RMGIC, Giomer and Compomer.
The fluoride re release was greatest on 1(st) day followed by rapid return to
near exposure levels. CONCLUSION: From the study it was concluded that, the
initial Fluoride release was highest from Conventional GIC followed by Resin
Modified GIC, Giomer and Compomer. The Fluoride re release was high when
recharging with professional regime (2% NaF) as compared to home regime
(Toothpaste). Conventional GIC had a greater recharging ability followed by Resin
Modified GIC, Giomer and Compomer.
PMID- 26436038
TI - Comparative Evaluation of Three Different Obturating Techniques Lateral
Compaction, Thermafil and Calamus for Filling Area and Voids Using Cone Beam
Computed Tomography: An Invitro study.
AB - INTRODUCTION: The success of root canal treatment depends upon the proper sealing
of root canal system. Improper apical seal leads to the microleakage which can be
prevented by proper obturation technique. AIM: To compare the quality of three
different root canal obturation techniques: lateral compaction, Thermafil and
Calamus by using cone beam computed tomography. MATERIALS AND METHODS: A total of
30 central incisors were selected. Biomechanical preparation was done by Reciproc
file no 25. Teeth were divided into 3 groups of 10 teeth each according to the
obturation technique i.e. Calamus, Thermafil and lateral compaction. Cone beam
computed tomography was used to measure filling area and voids at coronal, middle
and apical third of the root canal after obturation by different techniques. Data
was statistically analysed by One-Way Anova and multiple comparison of Tukey HSD
tests. RESULT: The maximum amount of obturating material was observed in Calamus
group followed by Thermafil and lateral compaction. Minimum voids were seen in
obturation by Calamus technique. CONCLUSION: Within the limitations of this
study, it can be concluded that Calamus may be a good obturation technique.
PMID- 26436039
TI - The Effect of Various Finish Line Configurations on the Marginal Seal and
Occlusal Discrepancy of Cast Full Crowns After Cementation - An In-vitro Study.
AB - BACKGROUND: The marginal fit of crowns is of clinical importance. It is found
that marginal and occlusal discrepancies are commonly increased following
cementation. The resistance of cementing materials is a factor that prevents cast
restorations from being correctly seated. Different finish lines behave
differently in facilitating the escape of the cement. When the escape path of the
cement decreases, the crown fails to seat further. MATERIALS AND METHODS: This
study was planned with an aim to evaluate the effect of various finish lines on
the marginal seal and occlusal seat of full crown preparations. Six stainless
steel metal dies were machined to simulate molar crown preparations. The diameter
was 10 mm and height was 6mm. The occlusal surface was kept flat and a small
circular dimple was machined for reorientation of the wax pattern and metal
copings, margins of various designs were machined accurately. The margins
prepared were Group A- 90(0)C shoulder, Group B- Rounded shoulder, Group C- 45
degree sloped shoulder, Group D- Chamfer, Group E- Long chamfer, Group F- Feather
edge. Full cast metal crowns of base metal alloy were fabricated over the metal
dies. Zinc phosphate luting cement was used for the cementation. After twenty
four hours, the cemented crown and die assembly were embedded in clear acrylic
resin so as to hold the assembly together while sectioning. Twenty four hours
later, all the samples were sectioned sagitally. The sectioned halves were
focused under a stereomicroscope and the cement spaces were measured to the
nearest micron. The cement thickness was measured at two points on the occlusal
surface and one at each margin. RESULTS: Significant differences were observed in
the occlusal seat and marginal seal of all the finish line configurations. The
rounded shoulder had the best occlusal seat, followed by 90(0)C shoulder. The
occlusal seat and marginal seal afforded by the shoulder finish lines were
similar whereas there was a vast difference in the seating and sealing of long
chamfer and feather edged preparations. They showed the worst occlusal seat.
CONCLUSION: It was found that the finish lines like shoulder preparations which
exhibit poor sealing prior to complete cementation allow good seating whereas
margins which seal earlier do not allow escape of cement and hence do not seat
completely.
PMID- 26436040
TI - A Noble, Easy and Conceptual Radiographic Analysis to Assess the Type of Tooth
Movement (Molar Distalization).
AB - CONTEXT AND AIM: Bodily tooth movement is desirable in the field of Orthodontics
and so is with molar distalization. Till date there is no such analysis available
which could gauge and quantify the molar distalization and the type of tooth
movement achieved, therefore one was required. MATERIALS AND METHODS: An OPG and
Lateral cephalogram was used taking Inter orbitale plane and FH plane
respectively as reference lines and the analysis was devised to measure the
amount and type of tooth movement achieved in distalization of molar. CONCLUSION:
This analysis is a noble, easy and conceptual analysis to assess the type of
tooth movement achieved during molar distalization and other molar movements
using Lateral cephalogram and orthopantomogram.
PMID- 26436041
TI - Effectiveness of CoQ10 Oral Supplements as an Adjunct to Scaling and Root Planing
in Improving Periodontal Health.
AB - INTRODUCTION: Deficiency of CoQ 10 was found in human inflamed gingiva and has
been found to be responsible for periodontal destruction. AIM: To evaluate the
effectiveness of CoQ 10 supplementation as an adjunct to scaling and rootplaning
in reducing gingival inflammation and periodontal pocket depth. MATERIALS AND
METHODS: The study was a randomized, double-blind, controlled, parallel group
design clinical trial. Thirty subjects with plaque induced gingival inflammation
and having atleast three nonadjacent interproximal sites with a probing pocket
depth >= 5mm were included in the study. The subjects were randomly divided into
two groups. The test group (n=15) in which patients were given oral CoQ10
supplements after scaling and root planing and the control group (n=15) in which
patients were given an oral placebo after scaling and rootplaning. The plaque
index, gingival index and probing depth were recorded at baseline, 1 month and 3
months. Statistical analysis done by using Student's paired t-test for intragroup
comparison and unpaired t-test for inter-group comparison. RESULTS: Both the
groups showed marked reduction of afore mentioned periodontal parameters at one
month and three months when compared to baseline. Though there was no significant
difference in plaque index and probing pocket depth between the two groups at any
given time period, test group showed significant difference in gingival
inflammation at one month and three months when compared to control group.
CONCLUSION: In the present study use of Coenzyme Q10 oral supplements as an
adjunct to scaling and root planing showed significant reduction in gingival
inflammation when compared to scaling and rootplaning alone.
PMID- 26436042
TI - Management of Chronic Periodontitis Using Subgingival Irrigation of Ozonized
Water: A Clinical and Microbiological Study.
AB - INTRODUCTION: Adjunctive use of professional subgingival irrigation with scaling
and root planing (SRP) has been found to be beneficial in eradicating the
residual microorganisms in the pocket. OBJECTIVE: To evaluate the effect of
ozonized water subgingival irrigation on microbiologic parameters and clinical
parameters namely Gingival index, probing pocket depth, and clinical attachment
level. MATERIALS AND METHODS: Thirty chronic periodontitis patients with probing
pocket depth >=6mm on at least one tooth on contra lateral sides of opposite
arches were included in the study. The test sites were subjected to ozonized
water subgingival irrigation with subgingival irrigation device fitted with a
modified subgingival tip. Control sites were subjected to scaling and root
planing only. The following clinical parameters were recorded initially and after
4 weeks at the test sites and control sites. Plaque Index, Gingival Index,
probing pocket depth, clinical attachment level. Microbiologic sampling was done
for the test at the baseline, after scaling, immediately after ozonized water
subgingival irrigation and after 4 weeks. In control sites microbiologic sampling
was done at the baseline, after scaling and after 4 weeks. The following
observations were made after 4 weeks. The results were statistically analysed
using independent t-test and paired t-test. RESULT: Test sites showed a greater
reduction in pocket depth and gain in clinical attachment compared to control
sites. The total anaerobic counts were significantly reduced by ozonized water
subgingival irrigation along with SRP compared to SRP alone. CONCLUSION: Ozonized
water subgingival irrigation can improve the clinical and microbiological
parameters in patients with chronic periodontitis when used as an adjunct to
scaling and root planing.
PMID- 26436043
TI - Direct Immunofluorescence in Oral Lichen Planus.
AB - INTRODUCTION: Oral lichen planus (OLP) is a common immune-mediated oral mucosal
disease. Diagnosis of OLP depends mainly on both clinical and histopathological
features. Direct immunofluorescence (DIF) is a useful investigation method to
distinguish between similar lesions and to confirm diagnosis in cases of
uncharacterized features. AIM: The purpose of this study was to evaluate the
prevalence and pattern of DIF in a group of Thai patients with OLP. MATERIALS AND
METHODS: Records of clinically and histologically diagnosed OLP patients
attending the Oral Medicine Clinic, Faculty of Dentistry, Mahidol University,
Bangkok, Thailand were consecutively reviewed for DIF results. The DIF patterns
in these patients were analysed. RESULTS: There were 82 atrophic and/or erosive
OLP patients with a mean age of 51.6 years. Male to female ratio was 1:5. Of
these, 82.9% showed positive DIF. Buccal mucosa was superior to the gingiva and
palate in terms of sensitivity for DIF. All specimens except one (98.5%)
demonstrated deposition of fibrinogen at the basement membrane zone (BMZ) in a
shaggy pattern. The most common DIF pattern was shaggy fibrinogen at BMZ with IgM
deposition on the colloid bodies (CB) (35.3%) followed by shaggy fibrinogen along
BMZ (27.9%). CONCLUSION: The prevalence of positive DIF in Thai OLP patients was
82.9%. The most common finding was shaggy fibrinogen at BMZ. The typical pattern
was shaggy fibrinogen along BMZ with or without positive IgM at CB. DIF pattern
could be evaluated for the diagnosis of OLP lacking clinical and/or
histopathological characteristic features.
PMID- 26436044
TI - Prevalence of Osteosclerosis Among Patients Visiting Dental Institute in Rural
Area of Western India.
AB - BACKGROUND: Idiopathic osteosclerosis (IO) is a benign lesion of unknown
aetiology and is not attributed to any dysplastic, inflammatory, neoplasia, or
systemic disorder. AIMS AND OBJECTIVES: To assess the prevalence and distribution
of IO according to its location and to patients' age and gender, among rural
population of western India. MATERIALS AND METHODS: Seven hundred and fifty
patients were examined for the presence of IO in the jaw bone. After a thorough
clinical examination, radiographic examination was done using OPG. Age specified
by WHO were used 5, 12, 15, 35-44 and 65-74. The data collected was than
tabulated and subjected to descriptive statistics and chi square test. RESULTS:
Among the total study population 89 (11.8%) were found to be suffering from IO
out of which 27 (7.2%) were males and 62 (16.53%) were females. The maximum
number of IO cases cases was seen among the age group of 35-44 y, 33 (22.0%) and
minimum in 5 y 9 (6%). CONCLUSION: IO is higher among the females as compared to
males and mostly seen among the 3(rd) and 4(th) decade individuals.
PMID- 26436045
TI - Knowledge and Awareness of Teledentistry among Dental Professionals - A Cross
Sectional Study.
AB - BACKGROUND: The use of technology in the form of smart phones and other
electronic media in day to day life has become an integral part of life today.
Technology today is seeing a paradigm shift towards better inter-professional
communications which can help doctors, patients and the masses as a whole.
Putting these technological advancements to good use evolves as a major milestone
in medicine/ dentistry in the form of telemedicine/teledentistry. AIM: The
present study was aimed at knowing the knowledge and awareness of teledentistry
among dental professionals of a dental college in India. SETTINGS AND DESIGN: The
study was conducted in a dental college in India and was circulated among dental
professionals. MATERIALS AND METHODS: A questionnaire was prepared to assess the
knowledge and awareness of teledentistry and was circulated among dental
professionals in a dental college. The data thus collected was statistically
analysed and results obtained. STATISTICAL ANALYSIS: The data collected was
statistically analysed using SPSS software. RESULTS: A total of 406 persons
responded to the questionnaire. In the present study it was found that the
knowledge and awareness about teledentistry was very low among post graduates
(7.23%) and interns (9.38%) when compared to I & II BDS while most of them agreed
that teledentistry is a practice of dentistry through various media options with
limited application in dentistry without a legal issue. CONCLUSION: In the
present study, it was apparent that most of the respondents were lacking adequate
knowledge and awareness on teledentistry. Hence, there is an immense need to
create awareness among dental professionals on teledentistry as the future lies
in technological advancement. Tele dentistry can mark the beginning of a new era
in dentistry. This can be achieved by conducting CDE programs and awareness
campaigns/programs which helps in various levels.
PMID- 26436046
TI - Association Between Harmful Oral Habits and Sign and Symptoms of
Temporomandibular Joint Disorders Among Adolescents.
AB - CONTEXT: Temporomandibular disorder (TDM) is defined as a heterogenous group of
psychophysiological disorders commonly characterised by orofacial pain, chewing
dysfunction or both. Various Epidemiological studies had shown occurrence of TMD
in all age groups including children. Also research had shown that non
nutritional oral habits to be associated with TMD. AIM: Present study aimed to
find whether harmful oral habits are associated with sign and symptoms of TMD
among adolescents in Greater Noida. SETTING AND DESIGN: Schools in Gautam Buddha
district and descriptive study. MATERIALS AND METHODS: Cross sectional study was
carried out among 240 adolescents (10 - 19 years) studying in schools of Greater
Noida. Study population were selected by random sampling to whom screening
questionnaires recommended by American Academy of Orofacial Pain (AAOP) were
distributed. Patient history and clinical examination was used to determine
harmful oral habits. Data analysis was done in SPSS version 21 and Chi-square
test was applied. RESULTS: Sixty one participants (25.4%) displayed no sign and
symptoms of TMD, 34 (14.2%) responded affirmatively to atleast one item on the
questionnaire and 108(46%) gave at least three affirmative responses. Headache,
Neckpain and Toothache were most frequent reported sign and symptoms of TMD
(46.2%). There was statistically significant association between gender and sign
and symptoms of TMD on three items of the questionnaire (p < 0.05). Nail Biting
(45.8%), Biting Lips/objects (37%) were most common habits among the study group.
There was statistically significant association between Nail Biting (p = 0.001),
Lip Biting/ object biting (p=0.001), Grinding of teeth (p = 0.01) and sign and
symptoms of TMD. CONCLUSION: A statistically significant association was found
between nail biting, lip/ object biting and grinding of teeth with signs and/or
symptoms of TMD. Thus there is need for preventive dental treatment and community
dental education so that young adults realize importance of early diagnosis and
treatment of TMJ disorders.
PMID- 26436047
TI - Awareness, Attitude and Barriers Towards Evidence Based Dental Practice Amongst
Practicing Dentists of Bhopal City.
AB - INTRODUCTION: Evidence based dental practice is said to be the recent best
approach to provide treatments or interventions, methodically proven to be safe
and sound, efficient and cost effective. So, for providing quality dental care,
clinical expertise, research evidence and patient's preferences all should be
given equal importance. AIM: To assess the awareness, attitude & barriers of
evidence-based dental practice (EBDP) amongst dentists of Bhopal city. MATERIALS
AND METHODS: The target population of this cross-sectional study involves
dentists of Bhopal city. Two hundred fifty private dentists of Bhopal were
selected using convenience sampling technique. Data was collected using a self
administered questionnaire containing 15 questions for assessing Knowledge,
attitude, practice & barriers in Evidence based practice. Chi-square, t-test &
one-way ANOVA were applied for data analysis and p<0.05 was considered
statistically significant. RESULTS: The study revealed that dental practitioners
had low knowledge about evidence based dental practices but they showed positive
attitude towards adopting it in their future practice. There exist certain
barriers in practice of evidence based dentistry. CONCLUSION: Including evidence
based dental practice teaching in dental curriculum may prove to be a significant
step in effective and efficient dental care delivery to the patients. Barriers in
evidence based practice needs to be identified & eliminated.
PMID- 26436048
TI - The Evaluation of Head and Craniocervical Posture among Patients with and without
Temporomandibular Joint Disorders- A Comparative Study.
AB - INTRODUCTION: Temporomandibular disorders (TMD) are the most common non-dental
cause of orofacial pain with a multifactorial aetiology. AIM: To evaluate the
head and craniocervical posture between individuals with and without TMD and its
sub types by photographic and radiographic method. MATERIALS AND METHODS: Thirty
four TMD patients diagnosed according to Research Diagnostic Criteria for TMD's
(RDC/TMD) and were divided into 2 groups: Group I (muscle disorder), Group II
(disc displacement). Control group comprised of 34 age and sex matched subjects
without TMD. Lateral view photographs were taken and the head posture angle was
measured. Craniocervical posture was assessed on lateral skull radiograph with
two angles (Craniocervical Angle, Cervical Curvature Angle) and two distances
(Suboccipital Space, Atlas-Axis Distance). To compare the results, t-test was
used with significance level of 0.05. RESULTS: Head posture showed no statistical
significant difference (p > 0.05) between Group I, II and control group in both
photographic and radiographic methods. The cervical curvature angle showed
significant difference (p = 0.045) in Group I only. Atlas-Axis Distance was
statistically significant in Group II (p = 0.001). CONCLUSION: The present study
confirmed that there is a negative association of head posture and TMD whereas,
cervical lordosis was present in Group I only.
PMID- 26436049
TI - Use of Curcumin Mouthrinse in Radio-Chemotherapy Induced Oral Mucositis Patients:
A Pilot Study.
AB - INTRODUCTION: Oral Mucositis is a complex and distinct pathobiologic entity
resulting in injuries in mucosa that is a common complication in cancer patients
undergoing chemotherapy (CT) and radiation therapy (RT). Phytochemicals, such as
Curcumin, turmeric extract, has attracted great attention for its therapeutic
benefits in clinical oncology due to its chemopreventive, antitumoral,
chemosensibilizing and radiosensibilizing activities against various types of
cancers and the complications associated with their management. AIM: To evaluate
the efficacy and safety of curcumin mouthwash in the management of Oral Mucositis
in cancer patients undergoing radio-chemotherapy. MATERIALS AND METHODS: The
research group consisted of 20 adult cancer patients undergoing radio
chemotherapy at the Regional Oncology Centre, who were evaluated for signs and
symptoms of oral mucositis and then randomly divided into two groups. Standard
preventive oral care i.e. chlorhexidine mouthwash 0.2% was given to one group
while the other group was provided with freshly prepared curcumin mouthwash; each
to be used thrice daily. Oral mucositis was assessed at days 0, 10 and 20. The
World Health Organization (WHO) scale, the Oral Mucositis Assessment Scale
(OMAS), and a Numerical Rating Scale (NRS; patient reporting scale of 0-10) were
used. Adverse events were tracked. STATISTICAL ANALYSIS: Descriptive statistics,
Independent sample t-test and repeated measure ANOVA test were performed.
RESULTS: Statistically significant difference was found in the NRS (p=0.000),
Erythema (p=0.050), ulceration (p=0.000) and WHO scores (p=0.003) between the two
groups. CONCLUSION: Curcumin was found to be better than chlorhexidine mouth wash
in terms of rapid wound healing and better patient compliance in management of
radio-chemotherapy induced oral mucositis. No oral or systemic complications were
reported.
PMID- 26436050
TI - Assessment of Tooth Wear Among Glass Factory Workers: WHO 2013 Oral Health
Survey.
AB - BACKGROUND: Glass factory workers are often exposed to the hazardous environment
that leads to deleterious oral health and subsequently, general health. We
planned to determine the effects of the particulates present in the milieu on the
tooth wear among workers. AIM: To assess tooth wear among glass factory workers
in Jaipur, Rajasthan, India. SETTINGS AND DESIGN: A descriptive cross-sectional
survey was conducted among 936 glass workers in Jaipur, Rajasthan, India from
January-June 2014. MATERIALS AND METHODS: A survey proforma was designed for
tooth wear evaluation with the help of WHO Oral Health Assessment form 2013 (for
adults). Information regarding oral health practices, adverse habits and dietary
habits, demographic details was gathered and clinical parameters were recorded.
STATISTICAL ANALYSIS: The Chi-square test, t-test, One-way Analysis of Variance
and a Stepwise multiple linear regression analysis. RESULTS: The most prevalent
form of erosion was enamel erosion (589, 62.93%) with few subjects of deeper
dentinal erosion and the difference was statistically significant (p=0.001).
Dental erosion was found to be higher among males compared to females. Years of
experience and educational status were identified as best predictors for dental
erosion. CONCLUSION: It was concluded that there was considerable evidence of
dental erosion found among the factory workers. Due to ignorance on social,
cultural and health aspects, professional approach with regular dental care
services for detection of early symptoms and planning of preventive strategies is
warranted.
PMID- 26436051
TI - Use of Clinical UV Chamber to Disinfect Dental Impressions: A Comparative Study.
AB - INTRODUCTION: Dental impressions are potential source of infection in a
prosthodontic practice. Risk of transmission of infection through saliva, blood
etc is considered as hazard for both dentist as well as dental auxiliary staff. A
number of methods are currently employed for disinfecting the impressions which
are technique sensitive and time consuming. This study focuses on disinfecting
impression using dental UV chamber which is commonly employed for storing
sterilized instruments. AIM: The aim of this invitro study was to evaluate the
use of clinical UV chamber to disinfect various impression materials at different
time intervals and its comparison with 2% glutaraldehyde using standard immersion
technique. MATERIALS AND METHODS: Total sample size of 180 specimens was taken
from three different impression materials. The impressions were made from 30
dentulous subjects. A total of ten impressions were made for each impression
material i.e. alginate, addition silicone and polyether impression material. Six
punch samples were taken from each impression. Out of 6 punch sample, one was
kept as control, second was disinfected by immersing in freshly prepared 2%
glutaraldehyde solution for 10 minutes and remaining four were exposed to UV rays
for 3 minutes, 6 minutes, 10 minutes and 15 minutes using dental UV chamber.
Amount of disinfection achieved was evaluated by counting the colonies over the
culture plates with the help of digital colony. RESULTS: The results showed that
the mean CFUs for alginate were found to be i.e. 11797.40 +/- 5989.73 (mean +/-
SD). The mean CFUs for addition silicone impression material was found 7095.40
with a standard deviation of 4268.83 and the mean CFUs for polyether impression
material was found to be 2168.92 +/- 1676 (mean +/- SD). CONCLUSION: For alginate
and addition silicone impression material, disinfection was achieved on exposure
to UV rays for a period of 10 minutes. However, for polyether impression material
3 minutes of exposure to UV rays was sufficient to cause complete disinfection.
PMID- 26436052
TI - Morphological Study of Soft Palate by Using Computed Tomography-A Prospective
Study.
AB - BACKGROUND: Soft palate is an important part of oro-naso-pharyngeal apparatus.
The morphometric assessment of soft palate is well-performed on computed
tomography (CT). AIM: To evaluate the morphology of soft palate in healthy
individuals by using Computed tomography. MATERIALS AND METHODS: The study was
conducted on 300 healthy voluntary participants who were subjected to CT scan
(sagittal view) of head and neck region. The measurements of antero-posterior and
supero-inferior length of soft palate were performed by using Syngo CT 2009E
software. STATISTICAL ANALYSIS: The statistical analysis was performed by using
SPSS software version 16 and test applied were one-way ANOVA, independent t-test,
chi-square and Karl Pearson's co-relation coefficient. RESULTS: The participant's
age ranged from 18-80 years with mean of 39.51+/-14.64. The study had equal
number of males (n=150) and females (n=150). Out of six shapes of soft palate,
Butt type (38.7%) was the commonest. The morphology of soft palate in different
age groups was statistically not significant (p>0.05). The total mean of antero
posterior length (30.31+/-3.39 mm) of soft palate was more than supero-inferior
length (10.72+/-1.71 mm). The mean of antero-posterior length in males (30.69+/
3.42 mm) was more than females (29.92+/-3.32 mm); which was statistically
significant (p<0.05). The mean of supero-inferior length in males (10.67+/-1.78
mm) was less than females (10.78+1.64 mm), which was statistically not
significant (p>0.05). CONCLUSION: CT scan is an important diagnostic aid for
studying the accurate morphology of soft palate.
PMID- 26436053
TI - Evaluation of Hi-Tec Implant Restoration in Mandibular First Molar Region- A
Prospective Clinical Study.
AB - BACKGROUND AND AIMS: Missing teeth lead to loss of structural balance,
inefficient function, poor aesthetics and psychological effects on human beings,
which needs restoration for normal contour, function and aesthetics. Several
natural or synthetic substitutes are being used for replacement of missing tooth
since centuries. Implants are the latest modality of replacement. So, the study
was aimed to assess clinical success rate of Hi-Tec implant; which is economical
and new in market. Results of the study will help clinician for appropriate
implant selection. MATERIALS AND METHODS: The study included 10 patients from 19
to 31 years and needed restoration of missing mandibular first molar. Restoration
had done using Hi Tec Single-tooth implants with metal-ceramic single crown
prosthesis after three months of osseointegration. The implants were evaluated
clinically (bleeding on probing, probing depth, implant mobility- periotest) and
radiographically (marginal bone loss and peri-implant radiolucency) for six
years. The observers were blinded for the duration of the study to prevent bias.
RESULTS: All the patients had uneventful post-surgical healing. No bleeding on
probing, Implant mobility, peri-implant radiolucency with minimal marginal bone
loss and constant probing depths were observed well within the normal range
during follow-up periods. CONCLUSION: Two stage single-tooth Hi Tec implant
restoration can be used as a successful treatment modality for replacing
mandibular first molar in an economic way. However, these results were obtained
after 6 years of follow up with a smaller sample size, so long term multi center
studies with a larger sample size is recommended for the predictability of
success rate conclusively.
PMID- 26436054
TI - Electromyographic Evaluation of the Effect of Lined Dentures on Masticatory
Muscle Activity in Edentulous Subjects.
AB - AIM: The purpose of this study was to examine changes in relative
electromyographic (EMG) activities of temporal and masseter muscles after
relining the dentures with silicone and acrylic-resin based denture liners.
MATERIALS AND METHODS: Conventional complete dentures were fabricated for 20
edentulous patients. One month after completing adjustments of the dentures,
electromyography of the masseter and temporalis muscle during maximum
intercuspation was recorded. The dentures were then relined with a silicone
denture liner and after an adaptation period of one month, were again subjected
for electromyographic evaluation. Further, the dentures were relined with acrylic
denture liner and subjected to electromyographic evaluation. Data was analysed
using Statistical Package for Social Sciences (SPSS) version 15.0. Intergroup
comparisons were done using ANOVA followed by post-hoc assessments using Tukey
HSD test. RESULTS: Mean amplitude and duration with conventional dentures was
found to be significantly lower as compared to silicone lined and acrylic lined
dentures for all the comparisons. Statistically, no significant difference
between silicone lined and acrylic lined dentures was observed for any of the
comparisons. CONCLUSION: Within the limitations of this experimental design, it
was concluded that relining significantly increases electromyographic activity of
the masseter and temporalis muscles. Thus, resulting in an improved biting force,
chewing efficiency and masticatory performance. There were no significant
differences between silicone and acrylic based denture liners for both
electromyographic variables.
PMID- 26436055
TI - Comparative Evaluation of Shear Bond Strength of Luting Cements to Different Core
Buildup Materials in Lactic Acid Buffer Solution.
AB - AIM AND OBJECTIVES: The core buildup material is used to restore badly broken
down tooth to provide better retention for fixed restorations. The shear bond
strength of a luting agent to core buildup is one of the crucial factors in the
success of the cast restoration. The aim of this invitro study was to evaluate
and compare the shear bond strength of luting cements with different core buildup
materials in lactic acid buffer solution. MATERIALS AND METHODS: Two luting
cements {Traditional Glass Ionomer luting cement (GIC) and Resin Modified Glass
Ionomer luting cement (RMGIC)} and five core buildup materials {Silver Amalgam,
Glass ionomer (GI), Glass Ionomer Silver Reinforced (GI Silver reinforced),
Composite Resin and Resin Modified Glass Ionomer(RMGIC)} were selected for this
study. Total 100 specimens were prepared with 20 specimens for each core buildup
material using a stainless steel split metal die. Out of these 20 specimens, 10
specimens were bonded with each luting cement. All the bonded specimens were
stored at 37(0)c in a 0.01M lactic acid buffer solution at a pH of 4 for 7days.
Shear bond strength was determined using a Universal Testing Machine at a cross
head speed of 0.5mm/min. The peak load at fracture was recorded and shear bond
strength was calculated. The data was statistically analysed using Two-way ANOVA
followed by HOLM-SIDAK method for pair wise comparison at significance level of
p<0.05. RESULTS: Two-Way ANOVA showed significant differences in bond strength of
the luting cements (p<0.05) and core materials (p<0.05) and the interactions
(p<0.05). Pairwise comparison of luting cements by HOLM-SIDAK test, showed that
the RMGIC luting cement had higher shear bond strength values than Traditional
GIC luting cement for all the core buildup materials. RMGIC core material showed
higher bond strength values followed by Composite resin, GI silver reinforced, GI
and silver amalgam core materials for both the luting agents. CONCLUSION: Shear
bond strength of RMGIC luting cement was significantly higher than traditional
GIC luting cement for all core buildup materials except, for silver amalgam core
buildup material. RMGIC core material showed highest shear bond strength values
followed by Composite resin, GI Silver Reinforced, GI and Silver Amalgam core
materials irrespective of luting cements.
PMID- 26436056
TI - Comparison of Effect of C-Factor on Bond Strength to Human Dentin Using Different
Composite Resin Materials.
AB - BACKGROUND: The study was planned to assess the use of low shrinkage composites
for restoring cavities with high configuration factor (C-factor) which are
subjected to high stresses. AIM: The aim of the study was to evaluate the effect
of C- factor on tensile bond strength to human dentin using methacrylate based
nanohybrid and low shrinkage silorane composite. MATERIALS AND METHODS: In this
study 40 non carious human molar teeth were selected and assigned into two main
groups - cavity (Class I cavity with high C-factor) and flat group (flat surface
with low C-factor). Two different composite materials- methacrylate based and
silorane low shrinkage composite were used to restore the teeth. Dentin surface
was treated, adhesive application was done and composite was applied as per
manufacturer's instructions. Samples were stored in distilled water then
subjected to tensile bond strength measurement using universal testing machine.
RESULTS: Statistical analysis was done using Independent sample t-test. The mean
bond strength in methacrylate based and silorane composite was significantly
higher in flat preparation (Low C-factor) than cavity preparation. The mean bond
strength in both cavity (High C-factor) and flat preparation(Low C-factor) was
significantly higher in silorane than in conventional methacrylate based
composite. CONCLUSION: The bond strength of composites to dentin is strongly
influenced by C-factor and type of composite resin material used.
PMID- 26436057
TI - Angiotensin II Levels in Gingival Tissues from Healthy Individuals, Patients with
Nifedipine Induced Gingival Overgrowth and Non Responders on Nifedipine.
AB - CONTEXT: The Renin Angiotensin system has been implicated in the pathogenesis of
Drug Induced Gingival Overgrowth (DIGO), a fibrotic condition, caused by
Phenytoin, Nifedipine and Cyclosporine. AIM: This study quantified Angiotensin II
levels in gingival tissue samples obtained from healthy individuals, patients on
Nifedipine manifesting/not manifesting drug induced gingival overgrowth.
MATERIALS AND METHODS: Gingival tissue samples were obtained from healthy
individuals (n=24), patients on nifidipine manifesting gingival overgrowth (n=
18) and patients on nifidipine not manifesting gingival overgrowth (n=8).
Angiotensin II levels were estimated in the samples using a commercially
available ELISA kit. RESULTS: Angiotensin II levels were significantly elevated
in patients on Nifedipine manifesting gingival overgrowth compared to the other 2
groups (p<0.01). CONCLUSION: The results of the study give an insight into the
role played by Angiotensin II in the pathogenesis of drug induced gingival
overgrowth.
PMID- 26436058
TI - Anaesthetic Efficacy of Topical Benzocaine Gel Combined with Hyaluronidase for
Supplemental Intrapulpal Injection in Teeth with Irreversible Pulpitis- A Double
Blinded Clinical Trial.
AB - OBJECTIVE: Intrapulpal injection technique is one of the most commonly employed
method to achieve profound pulpal anaesthesia during an endodontic procedure. To
determine if the topical application of benzocaine gel along with hyaluronidase
to the pulp chamber could reduce the pain felt with the intrapulpal injection
technique. MATERIALS AND METHODS: Two hundred patients with chronic irreversible
pulpitis undergoing endodontic treatment for mandibular first molars in which the
primary anaesthetic technique failed were selected and randomly divided into 2
groups. In the control group intrapulpal injection was administered with
backpressure. In the experimental group topical application of 20% benzocaine gel
mixed with hyaluronidase was done over the exposed pulp following which
intrapulpal injection was administered with backpressure. Pain assessment was
done on a visual analogue scale. RESULTS: There was statistically significant
difference (p<0.001) between the two groups. The mean value in the control group
corresponded to the pain perception "strong", whereas that of the experimental
group corresponded to the pain perception "weak". CONCLUSION: Topical application
of 20% benzocaine gel mixed with hyaluronidase to the exposed pulp reduces the
pain encountered with the intrapulpal injection.
PMID- 26436059
TI - Dimensional Changes of Alginate Dental Impression Materials-An Invitro Study.
AB - BACKGROUND: Dentists are always looking ahead for more dimensionally stable
material for accurate and successful fabrication of prosthesis in this
competitive world. Arrival of newer materials and increased material market puts
dentists in dilemma for selection of material. AIM: The study evaluated the
effect of variations in time of pour and temperature on dimensional stability of
three brands of commercially available alginates. MATERIALS AND METHODS:
Velplast, Marieflex & Zelgan alginate impression materials were evaluated by
measuring dimensional accuracy of the master cast. A die was prepared and mounted
on the apparatus for the ease of impression making. The prepared casts were
categorized into five groups and made up of three brands of alginate impression
material with variation in time of pour viz: immediate, 20&40 minutes interval
and with varying temperature of 25(0)C, 30(0)C & 40(0)C. RESULTS: Impressions
showed least distortion at varying degrees of temperature for 20 minutes, but the
values obtained by storing of alginate impressions for 20 minutes at 30(0)C were
found to be nearly accurate than the values obtained by storing of impression at
40(0)C. However, storing showed shrinkage of impressions. CONCLUSION: Marieflex
showed better accuracy in comparison with other two materials. Maintenance of
temperature and humidity play key role during storage & transport to prevent
distortion. But the study suggests immediate pouring which will minimize the
distortion. The manipulation instructions, temperature of mixing water,
environment & water powder ratio also plays key role in minimizing the
distortion.
PMID- 26436060
TI - Pathologic Surface Changes in the Submental Flap Used for Intraoral
Reconstruction: Report of Two Cases.
AB - Soft tissue reconstruction is often necessary after pathologic resection of oral
squamous cell carcinoma. Although morphologic changes are common after transfer
of the flaps to the oral cavity, pathologic changes within the transferred flaps,
used for intraoral reconstruction, are rare events. Despite the widespread use of
submental flap for oral cavity reconstruction, there are no reports in this
respect. In this article, pathologic changes in the surface epithelium of
transferred submental flaps are demonstrated with the report of two cases. The
occurrence of lichen planus in a submental flap that had been used for
reconstruction of lateral tongue border is reported in one case and in another
patient, squamous cell carcinoma arising in the transferred de-epithelialized
submental flap, used for maxillary and buccal reconstruction, is shown.
PMID- 26436061
TI - Conservative Management of Horizontal Root Fracture - A Case Series.
AB - Root fracture has been defined as a fracture involving dentin, cementum, pulp and
periodontal ligament. Depending on the level of the fracture line various
treatment modalities may be employed by the clinician to promote healing. The
following case reports highlight how changes in technique allow for conservative
management of horizontal root fractures at different levels. This approach allows
the patient to retain their natural dentition at an affordable cost and provide a
viable alternative to the use of more invasive and expensive alternatives. These
patients presented with complaints of pain and mobility in upper front tooth
region following trauma. Diagnosis was confirmed on the basis of intra-oral
periapical radiographs following which non-surgical root canal treatment was
performed.
PMID- 26436062
TI - Restoration of Long Standing Traumatized Teeth: A Case Report.
AB - Children are uniquely susceptible to craniofacial trauma. Injuries to the teeth
occur often as a result of falls and sport activities. The pulp often gets
infected after dental trauma resulting in to numerous complications. The authors
present a case report of successful restoration of traumatized teeth with open
apex which were weakened due to long standing infection and internal resorption.
Initially antibiotic combination of 3- mix was used to disinfect the root canals.
One tooth is treated with conventional endodontic treatment and the other tooth
with open apex and perforation is managed by MTA apexification followed by canal
reinforcement using glass ionomer cement and fiber reinforced composite post.
Core build up is done using light cure composite resin followed by aesthetic
crowns. The patient also presented with the peg shaped lateral incisors, which
were built to an aesthetic appearance using light cure composite resins.
PMID- 26436063
TI - Idiopathic Juvenile Osteoporosis: A Case Report.
AB - Idiopathic Juvenile Osteoporosis (IJO) is a very rare disease, self restrictive
and shows marked, spontaneous improvement during adolescence. The major clinical
features were pain with difficulty walking, growth retardation, oral and dental
abnormalities with radiographically porous bone structure. A 13-year-old male
referred to paediatric dentistry clinic for toothache. The observations made with
extra-intraoral clinic examination that one revealed short and skinny stature,
diffuse caries in deciduous teeth, abraded lower incisor, deep bite and
dysmorphic appearance in permanent incisor. This report emphasizes the recognized
features of IJO as well as describes facio-dental findings that could aid in the
diagnosis and management of these patients.
PMID- 26436064
TI - Surgical Approaches and Management of Panfacial Trauma: A Case Report.
AB - Patients with multiple fractures involving upper third of the face, the mid-face
and the lower third are generally referred to as Pan-facial fractures and
managing these cases is extremely complicated. Proximity of the maxillofacial
region to the important features or senses such as visual function (diplopia),
olfaction, respiration (airway management), chewing or mastication (occlusion),
deglutition and aesthetics; makes the scenario a little more complex for the
surgeon operating in this particular region than the surgeon operating any other
part of the body. Inability to directly visualize and reduce all the components
of a pan facial injury along with inadequate stability of the fractured bones
leads to persistent deformity. It is challenging to follow an established pattern
for repairing the pan facial fractures. Each case with this type of fracture is
unique and requires skill and expertise of the surgeon to restore the pre
traumatic anatomy and facial aesthetics. Despite all the aggressive treatment,
most of the patient's with pan facial trauma may have some residual deformity
which may require another correction surgery later. This article briefs about the
management and simple approaches used to reduce and fix a case of pan facial
trauma in a 23-year-old male.
PMID- 26436065
TI - Single Rooted Permanent Premolars and Molars - A Rare Clinical Presentation
Confirmed using Cone Beam Computed Tomography.
AB - The morphology of the root and root canal system plays a significant role in the
treatment outcome of endodontic procedures. The necessity of clear and high
contrast images for tissues like bone and teeth has made the usage of newer
imaging techniques inevitable. This is a rare case report wherein, the permanent
posterior dentition of both arches was single rooted. While sporadic cases of
single rooted teeth have been reported, it is rare for all the premolars and
molars to show such variation. This rare clinical observation has been enhanced
by Cone Beam Computed Tomography (CBCT), which provides a clear image with added
benefits of 3D (Three Dimensional) image reconstruction, low dosage and rapid
scan time.
PMID- 26436067
TI - Economical, Efficient, Simple Device for Controlled Annealing NiTi Archwire.
AB - In fixed orthodontic treatment, for the cinch back purpose, there is need of
annealing of distal end of NiTi arch wire. During this procedure the area or
length to be annealed is difficult to control. This inappropriate heating leads
to deleterious effect on property of the wire. To prevent this problem a simple
economical and efficient device was prepared that prevents annealing of excessive
length of wire and thus prevents the deterioration of wire required for
appropriate action.
PMID- 26436066
TI - Hyperactive Dental Lamina in a 24-Year-old Female - A Case Report and Review of
Literature.
AB - An extra tooth to the normal formula of teeth sequence in any region of dental
arch is regarded as Supernumerary teeth (ST). The reasons are still not clearly
known, one of them being dichotomy of tooth bud, but the more accepted reason is
the hyperactivity theory. Supernumerary teeth are present more in permanent
dentition than in primary dentition and can present as a single entity or
multiple, unilaterally or bilaterally, impacted or erupted, in either or both the
dental arches. This article discusses the supernumerary teeth in detail with a
case discussion of a non-syndromic 24-year-old girl, with six ST (bicuspids)
present in all the four quadrants. In the mandible, ST's showed a classical
clustered flower like presentation. The interesting feature in the presented case
was the sequential orthopantomographs taken at various ages of the patient that
showed continuous development of STs in all four quadrants, thus pointing to the
theory of hyperactive dental lamina or atavism. An electronic search was conceded
in PubMed, Cochrane Library and google scholar databases, and articles dated
between December 1932 and December 2012 were selected to review the occurrence
patterns of supernumerary teeth in non-syndromic cases.
PMID- 26436068
TI - Accidental Swallowing of Mandibular Partial Denture.
PMID- 26436069
TI - Role of Fenugreek in the prevention of type 2 diabetes mellitus in prediabetes.
AB - BACKGROUND: It is hypothesized that dietary supplementation with Fenugreek
modulates glucose homeostasis and potentially prevents diabetes mellitus in
people with prediabetes. The objective of present study is to determine whether
Fenugreek can prevent the outcome of T2DM in non diabetic people with
prediabetes. METHODS: A 3-year randomized, controlled, parallel study for
efficacy of Fenugreek (n = 66) and matched controls (n = 74) was conducted in men
and women aged 30-70 years with criteria of prediabetes. Fenugreek powder, 5 g
twice a day before meals, was given to study subjects and progression of type 2
diabetes mellitus (T2DM) was monitored at baseline and every 3 months for the 3
year study. RESULTS: By the end of intervention period, cumulative incidence rate
of diabetes reduced significantly in Fenugreek group when compared to controls.
The Fenugreek group also saw a significant reduction in fasting plasma glucose
(FPG), postprandial plasma glucose (PPPG) and low density lipoprotein cholesterol
(LDLc) whereas serum insulin increased significantly. It was observed that
controls had 4.2 times higher chance of developing diabetes compared to subjects
in the Fenugreek group. The outcome of diabetes in Fenugreek group was positively
associated with serum insulin and negatively associated with insulin resistance
(HOMA IR). CONCLUSIONS: Dietary supplementation of 10 g Fenugreek/day in
prediabetes subjects was associated with lower conversion to diabetes with no
adverse effects and beneficial possibly due to its decreased insulin resistance.
PMID- 26436070
TI - Heart and Lung Metastases From Endometrial Stromal Sarcoma in a Forty-Two-Year
Old Woman.
AB - INTRODUCTION: Low-grade endometrial stromal sarcoma (LG-ESS) is a malignant
intrauterine tumor that rarely presents with distant metastasis. Simultaneous
lung and cardiac metastases from LG-ESS is also an extremely rare event. CASE
PRESENTATION: A 42-year-old woman presented with dyspnea and exercise
intolerance. She had a history of hysterectomy and left salpingoophorectomy. She
underwent second laparotomy as well as right oophorectomy after new finding of
vaginal mass with histopathologic diagnosis of LG-ESS. Cardiac imaging techniques
demonstrated tumoral process in the right atrium and ventricle, coronary sinus,
and pulmonary outlet tract as well as multiple metastases in the lung fields.
Successful complete surgical resection of the metastatic tumor in the right side
of the heart and then radiotherapy were done. After 28 months, follow-up
examination revealed no abnormality. CONCLUSIONS: We describe the first
documented case of isolated intracardiac and lung metastases of a LG-ESS without
concurrent abdominal or caval metastasis.
PMID- 26436071
TI - Lower Doses of Bosentan in Combination With Sildenafil Might be Beneficial in
Pulmonary Arterial Hypertension.
AB - BACKGROUND: Endothelin-receptor-antagonist, bosentan, has been found to improve
the functional capacity and cardiopulmonary hemodynamics in Pulmonary Arterial
Hypertension (PAH). Clinical trials have shown the preferable dosage of 125 mg,
twice daily, regarding both efficacy and safety. OBJECTIVES: The purpose of this
study was to investigate the effects of lower doses of bosentan (62.5 mg, twice
daily) in combination with sildenafil on exercise capacity and clinical events,
in 41 patients with idiopathic pulmonary hypertension or chronic thromboembolic
pulmonary hypertension (CTEPH). PATIENTS AND METHODS: We assigned 41 patients
with PAH (non-reactive idiopathic or non-operable chronic thromboembolic) to
receive 62.5 mg of bosentan twice daily as combination therapy and evaluated the
New York heart association (NYHA) functional class, 6-minutes-walk-distance
(6MWD), time to clinical worsening, echocardiographic indexes and clinical
events, for an average of 18.5 +/- 9.5 months. RESULTS: No adverse drug reaction
was observed during the follow-up. Clinical worsening occurred in six (14%)
patients, at least one year after treatment, two of the cases failed to respond
to 125 mg, twice daily and died. Eight (19%) remained in FC I_II, but didn't
reach the goal of 380 meters for 6MWD. All other patients reached the treatment
goals according to the latest European society of cardiology (ESC) guidelines.
CONCLUSIONS: We observed acceptable results regarding both efficacy and safety
with 62.5 mg of bosentan, twice daily in this group of patients. Further clinical
trials investigating PAH with lower dosages of bosentan may be warranted.
PMID- 26436072
TI - Arrhythmogenic Risk Assessment Following Four-Week Pretreatment With Nicotine and
Black Tea in Rat.
AB - BACKGROUND: There is the controversy concerning the main component of tobacco,
which is responsible for its arrhythmogenesis. In addition, there is the lack of
adequate information about the influence of combination of black tea and nicotine
on heart rhythm. OBJECTIVES: This study aimed to examine whether pretreatment
with black tea and nicotine could modulate the susceptibility to lethal
ventricular arrhythmias. MATERIALS AND METHODS: Animals were randomized to
control, black tea, nicotine, and black tea plus nicotine groups. Test groups
were treated with black tea brewed (orally) and nicotine (2 mg/kg, subcutaneous),
alone and in combination for four weeks. On day 29, aconitine was infused
intravenously for induction of cardiac arrhythmia. RESULTS: In comparison with
the control group, each of tea and nicotine significantly decreased the duration
of the ventricular tachycardia (VT) plus ventricular fibrillation (VF) and the
score of arrhythmia severity (P < 0.05 and P < 0.01, respectively,). The latency
for the first VT event was significantly longer in the all test groups, but VF
latency was significant only in tea and nicotine groups compared with control
group (P < 0.05 and P < 0.01, respectively).Threshold dose of aconitine for
inducing VT and VF increased in all test groups, but only VT showed a significant
difference in comparison to the control group (P < 0.001). CONCLUSIONS: The
findings suggest that sub-chronic consumption of nicotine or black tea alone with
appropriate doses could potentially be antiarrhythmic and its combination regimen
does not increase the risk of fatal ventricular arrhythmias during four-week
consumption period in rats.
PMID- 26436073
TI - Anesthetic Management in a Patient With Type A Aortic Dissection and Superior
Vena Cava Syndrome.
AB - INTRODUCTION: Induction of general anesthesia in patients with superior vena cava
(SVC) syndrome may cause airway obstruction and cardiovascular collapse. CASE
PRESENTATION: Herein, we introduced a patient with the diagnosis of dissecting
aneurysm of the ascending aorta who was candidate for emergency surgery. He also
had symptoms of SVC syndrome. To maintain airway patency during anesthetic
management, we decided to perform femoro-femoral cardiopulmonary bypass followed
by general anesthesia and tracheal intubation. CONCLUSIONS: Femoro-femoral bypass
prior to initiation of sternotomy is a safe and easy method in patients with
aortic dissection and SVC syndrome in whom earlier endotracheal intubation may
not be feasible.
PMID- 26436074
TI - Avoiding Heparinization of Arterial Line and Maintaining Acceptable Arterial
Waveform After Cardiac Surgery: A Randomized Clinical Trial.
AB - BACKGROUND: Invasive and continuous blood pressure (BP) monitoring is crucial
after cardiac surgery. Accuracy of BP measurement mostly depends on patency of
arterial catheter and acceptable waveform. Heparinized saline flush usually used
for this purpose may be accompanied by potential heparin adverse effects.
OBJECTIVES: The aim of this study was to compare heparinized and non-heparinized
saline flush to maintain acceptable arterial waveform after cardiac surgery.
MATERIALS AND METHODS: In a double blind randomized trial study, 100 patients
undergoing elective cardiac surgery were randomized to using heparinized (n = 50)
or non-heparinized (normal) saline flush (n = 50) to maintain patency of arterial
catheter after operation. Indwelling arterial catheters were checked daily for
acceptable arterial waveform for three days as primary outcome measures. RESULTS:
Frequency of acceptable arterial waveform ranged from 66% to 80%, in first,
second and third postoperative days. There were no statistically significant
differences between heparinized and non-heparinized saline groups regarding
acceptable arterial waveforms in all the three postoperative days (all P values >
0.05). CONCLUSIONS: Using non-heparinized normal saline is suitable to maintain
acceptable arterial waveform for short-term (three days) after adult cardiac
surgery considering potential adverse effects of heparin.
PMID- 26436075
TI - Inferior Vena Cava and Hemodynamic Congestion.
AB - BACKGROUND: Among the indices able to replace invasive central venous pressure
(CVP) measurement for patients with acute decompensated heart failure (ADHF) the
diameters of the inferior vena cava (IVC) and their respiratory fluctuations, so
called IVC collapsibility index (IVCCI), measured by echocardiography, have
recently gained ground as a quite reliable proxy of CVP. OBJECTIVES: The aims of
our study were to compare three different ways of evaluating cardiac overload by
using the IVC diameters and/or respiratory fluctuations and by calculating the
inter-method agreement. PATIENTS AND METHODS: Medical records of patients
hospitalized for right or bi-ventricular acute decompensated heart failure from
January to December 2013 were retrospectively evaluated. The predictive
significance of the IVC expiratory diameter and IVC collapsibility index (IVCCI)
was analyzed using three different methods, namely a) the criteria for the
indirect estimate of right atrial pressure by Rudski et al. (J Am Soc
Echocardiogr. 2010); b) the categorization into three IVCCI classes by Stawicki
et al. (J Am Coll Surg. 2009); and c) the subdivision based on the value of the
maximum IVC diameter by Pellicori et al. (JACC Cardiovasc Imaging. 2013).
RESULTS: Among forty-seven enrolled patients, those classified as affected by
persistent congestion were 22 (46.8%) using Rudski's criteria, or 16 (34%) using
Stawicki's criteria, or 13 (27.6%) using Pellicori's criteria. The inter-rater
agreement was rather poor by comparing Rudski's criteria with those of Stawicki
(Cohen's kappa = 0.369; 95% CI 0.197 to 0.54), as well as by comparing Rudski's
criteria with those of Pellicori (Cohen's kappa = 0.299; 95% CI 0.135 to 0.462).
Further, a substantially unsatisfactory concordance was also found for Stawicki's
criteria compared to those of Pellicori (Cohen's kappa= 0.468; 95% CI 0.187 to
0.75). CONCLUSIONS: The abovementioned IVC ultrasonographic criteria for
hemodynamic congestion appear clearly inconsistent. Alternatively, a sequential
or simultaneous combination of clinical scores of congestion, IVC
ultrasonographic indices, and circulating levels of natriuretic peptides could be
warranted.
PMID- 26436077
TI - The Schwartz-Jampel syndrome: Case report and review of literature.
AB - Schwartz-Jampel syndrome (SJS), first described in the United States in 1962, is
a hereditary disorder characterized by facial dysmorphism and muscle stiffness.
We describe the first case of a Persian 9-year-old boy with SJS and review the
literature. The child had a short neck, blepharophimosis, flattened face,
hypertrichosis of the eyelids, prominent eyebrows, high arched palate, low set
ears, micrognathia, short stature, and skeletal deformities. He had proximal
muscle hypertrophy, distal muscle wasting and generalized hyporeflexia. Bone X
ray revealed pseudofracture of humerus. Needle electromyography revealed
continuous myotonic discharges at rest with no waxing and waning in all tested
muscles. Based on clinical and electrodiagnostic findings, the diagnosis of SJS
type 1B was made and procainamide was started which resulted in clinical
improvement. The diagnosis of SJS should be suspected when a child presents with
the triad of myotonia, facial dysmorphism and skeletal deformities.
PMID- 26436076
TI - Distribution of cytokine gene single nucleotide polymorphisms among a multi
ethnic Iranian population.
AB - BACKGROUND: Cytokine gene single nucleotide polymorphisms (SNPs) are widely used
to study susceptibility to complex diseases and as a tool for anthropological
studies. MATERIALS AND METHODS: To investigate cytokine SNPs in an Iranian multi
ethnic population, we have investigated 10 interleukin (IL) SNPs (IL-1beta (C
511T, T-31C), IL-2 (G-384T), IL-4 (C-590T), IL-6 (G-174C), IL-8 (T-251A), IL-10
(G-1082A, C-819T, C-592A) and tumor necrosis factor-alpha (TNF-alpha) (G-308A) in
415 Iranian subjects comprising of 6 different ethnicities. Allelic and genotypic
frequencies as well as Hardy-Weinberg equilibrium (HWE) were calculated by PyPop
software. Population genetic indices including observed heterozygosity (Ho),
expected heterozygosity (He), fixation index (FIS), the effective number of
alleles (N e) and polymorphism information content (PIC) were derived using
Popgene 32 software. Multidimensional scaling (MDS) was constructed using
Reynold's genetic distance obtained from the frequencies of cytokine gene
polymorphism. RESULTS: Genotypic distributions were consistent with the HWE
assumptions, except for 3 loci (IL-4-590, IL-8-251 and IL-10-819) in Fars and 4
loci (IL-4-590, IL-6-174, IL-10-1082 and TNF-alpha-308) in Turks. Pairwise
assessment of allelic frequencies, detected differences at the IL-4-590 locus in
Gilakis versus Kurds (P = 0.028) and Lurs (P = 0.022). Mazanis and Gilakis
displayed the highest (Ho= 0.50 +/- 0.24) and lowest (Ho= 0.34 +/- 0.16) mean
observed heterozygosity, respectively. CONCLUSIONS: MDS analysis of our study
population, in comparison with others, revealed that Iranian ethnicities except
Kurds and Mazanis were tightly located within a single cluster with closest
genetic affinity to Europeans.
PMID- 26436078
TI - Comparison of emotional and non-emotional word repetitions in patients with
aphasia.
AB - BACKGROUND: Aphasia is a language disorder caused by left hemisphere damage. For
treatment of aphasia, in some of therapeutic approaches, the right hemisphere
(RH) abilities, such as, emotional perception, is used for stimulation of the
language process in the left hemisphere. The aim of this study is to investigate
emotional word repetition in aphasia after a stroke, in Persian language
patients. MATERIALS AND METHODS: Fifteen aphasic patients (eleven male and four
female) between 45 and 65 (58/4 +/- 7/8) years of age, participated in this cross
sectional study. A list of 20 emotional words and a list of 20 neutral words as
stimuli were prepared and the patients were asked to repeat each word after five
seconds; if a patient needed to repeat a word again, it was repeated for him/her
again, and the total score for each subject was calculated. The paired t-test was
used to test group mean differences and the significant level was 0.05. RESULTS:
The mean and standard deviation for emotional word repetitions were 6.93 +/- 1.72
and for non-emotional word repetition was 7.10 +/- 2.23, and the P value = 0.892,
thus, no significant difference between emotional and non-emotional word
repetitions was noticed. The mean and standard deviation for the positive
emotional word repetitions were 3.53 +/- 3.29 and for negative word repetitions
were 3.40 +/- 3.56, (P = 0.751), with no significant difference between positive
and negative emotional word repetitions. CONCLUSION: Despite the main hypothesis
that the right hemisphere is involved in the processing of emotions, it can be
stated that both hemispheres are involved in the processing of emotional words,
albeit in a different and probably complementary manner.
PMID- 26436079
TI - Preliminary study on patients located at the Kashani/Isfahan Hospital with
multiple sclerosis between the years 2011 and 2013.
AB - BACKGROUND: Multiple sclerosis (MS) is a multifactorial disease that could result
from demyelination of the myelin sheath. The aim of this study is to investigate
the demographic features and rank the immunomodulating drugs in patients with MS.
MATERIALS AND METHODS: This study was conducted in the MS clinic of the Isfahan
Kashani Hospital, from 22 May, 2011 to 18 March, 2013. The data analyses (n =
1067) were divided into two periods: (1) 2011/05/22 to 2012/03/18 denoted as P1
and (2) 2012/04/02 to 2013/03/18 denoted as P2. RESULTS: Most of drugs prescribed
within the population studied were: Avonex, Betaferone, and Rebif. There was an
increase in the number of female (n = 811) and male subjects (n = 256). During
P1/P2 there was an increase from 460 to 607 in the total number of patients,
respectively. The number of patients who attended the MS clinic once was 250 (P1)
versus 430 (P2), and those more than four times was 71 (P1) versus 59 (P2)
correspondingly. CONCLUSION: The number of females increased from 2011 to 2013.
Because of dissimilar ingredients additive of different pharmaceutical companies,
it could be suggested that pharmacotherapy strategies, especially in Iranian
population of MS with first-line treatment using Avonex, Betaferone and Rebif,
more spotlighted on inter- and intra-individual variability based on clinical
pharmacokinetics parameters.
PMID- 26436080
TI - Preliminary analysis of month of birth in Iranian/Isfahan patients with multiple
sclerosis.
AB - BACKGROUND: Previous publications reported that an individual's month of birth
(MOB) might have an important correlation to that consequent risk of multiple
sclerosis (MS). AIM: The aim of this preliminary study was to investigate the
distribution of different MOBs inpatients with MS in Isfahan, Iran. MATERIALS AND
METHODS: This investigation was conducted to the Isfahan Neurosciences Research
Centre. 1283 patients with MS were studied. Clinical data were recorded in d-Base
and analyzed using SPSS (version 18) for Windows. RESULTS: Of the total
population studied there were 979 females and 304 males. The mean age of all the
patients was 34.6 years (range 10-87 years). Within the total population, the
MOBs in the 62% of patients were in the season's spring and summer, and in 38% of
patients they were in the season's autumn and winter. As the MOB might be
recognized to have a bearing on an individual's risk of contracting MS, the
highest and lowest correlations seem to be linked with April, September, May (?),
and November (?), respectively. CONCLUSIONS: The seasonal relationship between
MOBs and MS risk might be pointed toward a potential function for vitamin D
throughout pregnancy or the early life of the newborn. Further studies are needed
to confirm these correlations.
PMID- 26436081
TI - Effect of omega-3 supplementation on inflammatory parameters in patients on
chronic ambulatory peritoneal dialysis.
AB - BACKGROUND: End stage renal disease (ESRD) is a state of micro inflammation that
attenuates patient's life span and quality of life. Inflammatory markers like
interlukin 6 (IL-6) and C- reactive protein (CRP) can predict inflammatory state
in ESRD patients. Dietary limitations are risk factors for omega-3 deficiency in
these patients. Omega-3 supplementation is an attractive material that proposed
in inflammation modulation. The aim of this study is evaluation of effect of
omega-3 supplementation on IL-6 and CRP level in chronic ambulatory peritoneal
dialysis (CAPD) patients. MATERIALS AND METHODS: This randomized controlled
double-blind clinical trial is performed in 40 CAPD patients in two academic
hospitals in Isfahan, Iran. One group received 1000 mg omega-3 capsule (each
capsule contains 180 mg Eicosapentanoic and 120 mg Dosahexanoic acid) three times
a day orally for 8 weeks (n = 20) and the other matched group by placebo (n =
20). Serum level of IL-6 and quantitative CRP (Q-CRP) were measured in beginning
and the end of the study. Finally all data were analyzed by SPSS version 18.
RESULTS: Mean age of patients was 53 years old in omega-3 group patients and 54
years old in placebo group. There were not any differences in CRP and IL-6 level
in the beginning and the end of study between two groups (P: 0.81 and 0.10 for
CRP and 0.26 and 0.23 for IL-6, respectively). CONCLUSION: Omega-3
supplementation did not effect on inflammatory markers (Q-CRP and IL-6) in CAPD
patients after 8 weeks.
PMID- 26436082
TI - The relationship between quality of life and coping strategies in polycystic
ovary syndrome patients.
AB - BACKGROUND: There are many factors that affect the quality of life, for example,
stress and the coping strategies. Polycystic ovary syndrome is a common hormonal
disorder leading to menstrual disorders, hirsutism, acne, obesity, infertility
and abortion. In such cases, the patients suffer from a variety of stresses and
face problems in their coping strategies with life's problems which can affect
the quality of life and cause psychological distress and low the quality of life.
The quality of life is a descriptive term which points to health and emotional,
social and physical promotion of individuals as well as their ability to perform
daily living tasks. The purpose of this study was to investigate the relationship
between quality of life and coping strategies in patients with polycystic ovary
syndrome. MATERIALS AND METHODS: To perform this study, randomly 200 women who
had inclusion criteria and were referred to Ali Shariati Hospital in Isfahan were
selected and responded DLQI questionnaire and Carver coping strategies and form
of demographic characteristics. RESULTS: The mean score of quality of life in the
patients was 4.14 +/- 5.57. It was shown that acne has no effective role on
quality of life and coping strategies in contrast in hirsute and non-hirsute
patients; there was a significant difference in quality of life P value < 0.001).
Also there is a significant relationship between the quality of life and coping
strategies (problem solving, cognitive, emotional and social support) (P < 0.05)
and quality of life has the highest correlation with emotional strategies (r =
0.46). CONCLUSION: According to results of this study, patients with PCOS are at
risk pcychologicla disorders that may be led to decrease of quality of life. Thus
this patients need to support by oppositions strategies. Also not only physical
treatment but also psychological surveillance especially social support must be
done for them.
PMID- 26436083
TI - Two unusual sites of cystic lymphangioma in a child: A report of imaging profile
with surgical and histopathologic findings.
AB - Cystic lymphangioma (CL) is a benign lymphatic malformation mostly seen in the
head and neck of neonates and infants. Abdominal CL is an unusual entity which
may present in omentum, mesentery, abdominal wall, or solid organs. The authors
present an unusual case with two separate abdominal cystic lymphangiomas.
PMID- 26436084
TI - Herpes zoster segmental paresis in an immunocompromised breast cancer woman.
AB - Herpes zoster is an infectious disease with neurological complications caused by
reactivation of varicella zoster virus in dorsal root ganglia of spinal cord
which is also known as "Shingles." Suppression of immune system is the major
predisposing factor for reactivation of latent virus. Disease is mainly
characterized by rash, vesicles and pain along one or more dermatomes which are
innervated from one or more spinal nerve roots. Complications may be present
after a while despite of patient treatment. Motor involvement is included. Some
previous studies showed segmental zoster paresis as a rare complication, a few
weeks after first presentation, among immunocompetent individuals. We present
post herpetic motor involvement of C5 and C6 in a 59-year-old woman who underwent
chemotherapy and radiotherapy due to breast cancer, manifesting left upper limb
weakness and paresis, 6 months after left partial mastectomy. Segmental paresis
of zoster virus should be considered as a cause of motor impairment in an
immunocompromised person suffering from shingles.
PMID- 26436085
TI - Targeted Therapy in Hematological Malignancies: From Basic Research to Clinical
Practice.
PMID- 26436086
TI - Missense Mutations in Exons 18-24 of EGFR in Hepatocellular Carcinoma Tissues.
AB - Epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase
receptor, plays important roles in various cancers. In nonsmall cell lung cancer
(NSCLC), EGFR mutations cluster around the ATP-binding pocket (exons 18-21) and
some of these mutations activate the kinase and induce an increased sensitivity
to EGFR-tyrosine kinase inhibitors. Nevertheless, data of EGFR mutations in HCC
are limited. In this study, we investigated EGFR expression by
immunohistochemistry and EGFR mutations (exons 18-24) by PCR cloning and
sequencing. EGFR overexpression in HCC and matched nontumor tissues were detected
in 13/40 (32.5%) and 10/35 (28.6%), respectively. Moreover, missense and silent
mutations were detected in 13/33 (39.4%) and 11/33 (33.3%) of HCC tissues,
respectively. The thirteen different missense mutations were p.L730P, p.V742I,
p.K757E, p.I780T, p.N808S, p.R831C, p.V851A, p.V897A, p.S912P, p.P937L, p.T940A,
p.M947V, and p.M947T. We also found already known SNP, p.Q787Q (CAG>CAA), in
13/33 (39.4%) of HCC tissues. However, no significant association was detected
between EGFR mutations and EGFR overexpression, tissue, age, sex, tumor size,
AFP, HBsAg, TP53, and Ki-67. Further investigation is warranted to validate the
frequency and activity of these missense mutations, as well as their roles in HCC
tumorigenesis and in EGFR-targeted therapy.
PMID- 26436087
TI - Recent Advances in Genetic Technique of Microbial Report Cells and Their
Applications in Cell Arrays.
AB - Microbial cell arrays have attracted consistent attention for their ability to
provide unique global data on target analytes at low cost, their capacity for
readily detectable and robust cell growth in diverse environments, their high
degree of convenience, and their capacity for multiplexing via incorporation of
molecularly tailored reporter cells. To highlight recent progress in the field of
microbial cell arrays, this review discusses research on genetic engineering of
reporter cells, technologies for patterning live cells on solid surfaces,
cellular immobilization in different polymers, and studies on their application
in environmental monitoring, disease diagnostics, and other related fields. On
the basis of these results, we discuss current challenges and future prospects
for novel microbial cell arrays, which show promise for use as potent tools for
unraveling complex biological processes.
PMID- 26436089
TI - Comment on "Nontuberculous Mycobacteria Isolation from Clinical and Environmental
Samples in Iran: Twenty Years of Surveillance".
PMID- 26436088
TI - MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to
Chemoresistance.
AB - MicroRNAs (miRs) play an important role in tumorogenesis and chemoresistance in
lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was
overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T
cell lymphoblastic leukemia (n = 32), T-cell lymphoblastic lymphoma (n = 16),
peripheral T-cell lymphoma, not otherwise specified (n = 45), anaplastic large
cell lymphoma (n = 15), and angioimmunoblastic T-cell lymphoma (n = 22).
Irrespective to histological subtypes, miR181a overexpression was associated with
increased AKT phosphorylation. In vitro, ectopic expression of miR181a in HEK
293T cells significantly enhanced cell proliferation, activated AKT, and
conferred cell resistance to doxorubicin. Meanwhile, miR181a expression was
upregulated in Jurkat cells, along with AKT activation, during exposure to
chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment,
such as doxorubicin, cyclophosphamide, cytarabine, and cisplatin. Isogenic
doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also
presented with miR181a overexpression and cross-resistance to cyclophosphamide
and cisplatin. Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9
cell sensitivity to chemotherapeutic agents, further indicating that miR181a was
involved in acquired chemoresistance. Collectively, miR181a functioned as a
biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway. Related
to tumor cell chemoresistance, miR181a could be a potential therapeutic target in
treating T-cell malignancies.
PMID- 26436090
TI - Efficacy of Biodentine as an Apical Plug in Nonvital Permanent Teeth with Open
Apices: An In Vitro Study.
AB - The aim of this study was to evaluate the apical microleakage of Biodentine and
MTA orthograde apical plugs and to compare the effect of thickness of these
biomaterials on their sealing ability. A total of eighty maxillary anterior teeth
were used. The apices were removed by cutting with a diamond disc (Jota, Germany)
2 mm from the apical root end in an attempt to standardize the working length of
all specimens to 15 +/- 1 mm. Both materials were placed in 1-4 mm thickness as
apical plugs root canal. Root canal leakage was evaluated by the fluid filtration
technique. One-way ANOVA was used in order to determine normality of dispersal
distribution of parameters; thereafter, results were analyzed by Kolmogorov
Smirnov test. Overall, between microleakage values of MTA and Biodentine
regardless of apical plug thickness, no difference was observed. In terms of plug
thickness, a statistically significant difference was observed between the
subgroups of MTA and Biodentine (p < 0.05). The apical sealing ability of
Biodentine was comparable to MTA at any apical plug thickness.
PMID- 26436091
TI - Computational and Theoretical Analysis of Human Diseases Associated with
Infectious Pathogens.
PMID- 26436092
TI - Changes in B-Cell Counts and Percentages during Primary HIV Infection Associated
with Disease Progression in HIV-Infected Men Who Have Sex with Men: A Preliminary
Study.
AB - Numerous anomalies in B-cell phenotypes and functions have been described in HIV
infected individuals. However, the actual relationship between B cells and
disease progression remains unclear. In this study, we investigated B-cell
counts/percentages during a 12-month infection period in HIV-infected individuals
that eventually developed into typical progressors (TPs) or rapid progressors
(RPs). We found, after 12 months of infection, the baseline B-cell
counts/percentages correlated positively with CD4(+) T-cell counts (P = 0.0006
and P = 0.026) and negatively with HIV viral set points (P = 0.014 and P =
0.002). Kaplan-Meier survival analysis showed that high baseline B-cell
counts/percentages were associated with a slow CD4-cell decline. B-cell kinetics
indicated the baseline B-cell counts/percentages could be factors distinguishing
between TPs and RPs. The combination of the baseline B-cell counts and
percentages was associated with rapid disease progression (a 80.7% predictive
value as measured by the area under the curve). These results indicate that the
baseline B-cell counts/percentages might be associated with HIV disease
progression.
PMID- 26436093
TI - Using PET/CT Bone Scan Dynamic Data to Evaluate Tibia Remodeling When a Taylor
Spatial Frame Is Used: Short and Longer Term Differences.
AB - Eighteen consecutive patients, treated with a Taylor Spatial Frame for complex
tibia conditions, gave their informed consent to undergo Na(18)F(-) PET/CT bone
scans. We present a Patlak-like analysis utilizing an approximated blood time
activity curve eliminating the need for blood aliquots. Additionally,
standardized uptake values (SUV) derived from dynamic acquisitions were compared
to this Patlak-like approach. Spherical volumes of interest (VOIs) were drawn to
include broken bone, other (normal) bone, and muscle. The SUV m (t) (m = max,
mean) and a series of slopes were computed as (SUV m (t i ) - SUV m (t j ))/(t i
t j ), for pairs of time values t i and t j . A Patlak-like analysis was
performed for the same time values by computing ((VOI p (t i )/VOI e (t i ))-(VOI
p (t j )/VOI e (t j )))/(t i - t j ), where p = broken bone, other bone, and
muscle and e = expected activity in a VOI. Paired comparisons between Patlak-like
and SUV m slopes showed good agreement by both linear regression and correlation
coefficient analysis (r = 84%, r s = 78%-SUVmax, r = 92%, and r s = 91%-SUVmean),
suggesting static scans could substitute for dynamic studies. Patlak-like slope
differences of 0.1 min(-1) or greater between examinations and SUVmax differences
of ~5 usually indicated good remodeling progress, while negative Patlak-like
slope differences of -0.06 min(-1) usually indicated poor remodeling progress in
this cohort.
PMID- 26436094
TI - Efficacy Study of Broken Rice Maltodextrin in In Vitro Wound Healing Assay.
AB - Maltodextrins that contain both simple sugars and polymers of saccharides have
been widely used as ingredients in food products and pharmaceutical delivery
systems. To date, no much work has been reported on the applications of
maltodextrin from broken rice (RB) sources. Therefore, the objective of this work
was to investigate the in vitro wound healing efficacy of RB maltodextrin at
different conditions. Wounds treated with lower dextrose equivalent (DE) range
(DE 10-14) of maltodextrins at a concentration of 10% obtained from RB were found
to be able to heal the wounds significantly faster (p < 0.01) than maltodextrin
with higher DE ranges (DE 15-19 and DE 20-24) and concentrations of 5% and 20%.
The findings from both BrdU and MTT assay further confirmed its wound healing
properties as the NIH 3T3 fibroblast wounded cells were able to proliferate
without causing cytotoxic effect when wounded cell was treated with maltodextrin.
All these findings indicated that the RB maltodextrin could perform better than
the commercial maltodextrin at the same DE range. This study showed that RB
maltodextrins had better functionality properties than other maltodextrin sources
and played a beneficial role in wound healing application.
PMID- 26436095
TI - Bioinformatics Methods and Biological Interpretation for Next-Generation
Sequencing Data.
PMID- 26436096
TI - The Effect of Covalently Immobilized FGF-2 on Biphasic Calcium Phosphate Bone
Substitute on Enhanced Biological Compatibility and Activity.
AB - The purpose of this research was to covalently graft fibroblast growth factor 2
(FGF-2) onto biphasic calcium phosphate (BCP) via a bifunctional cross-linker
technique and to estimate the optimal dose of FGF-2 resulting in the best
osteogenic differentiation of human mesenchymal stem cells (hMSCs). SEM
observation revealed that the surface of the 100 ng FGF-2 coated BCP was
completely covered with the nanoparticles expected to be from the silane coupling
agent. XRD, FT-IR, and XPS analysis showed that silane treatment, bifunctional
cross-linker coating, and FGF-2 covalent grafts were conducted successfully
without deforming the crystalline structure of BCP. An MTT assay demonstrated
that FGF-2 coated BCP had good biocompatibility, regardless of the concentration
of FGF-2, after 24 or 48 h of incubation. An alkaline phosphatase (ALP) activity
assay (14 days of incubation) and the ALP gene expression level of real-time PCR
analysis (7 days of incubation) revealed that 50, 100, and 200 ng FGF-2 coated
BCP induced the highest activities among all experimental groups and control
group (P < 0.05). Thus, low concentrations of FGF-2 facilitated excellent
osteogenesis and were effective at enhancing osteogenic potential. Also, the
bifunctional cross-linker technique is expected to be a more feasible way to
induce osteogenic differentiation while minimizing the risk of FGF-2 overdose.
PMID- 26436097
TI - Surface Modifications and Their Effects on Titanium Dental Implants.
AB - This review covers several basic methodologies of surface treatment and their
effects on titanium (Ti) implants. The importance of each treatment and its
effects will be discussed in detail in order to compare their effectiveness in
promoting osseointegration. Published literature for the last 18 years was
selected with the use of keywords like titanium dental implant, surface
roughness, coating, and osseointegration. Significant surface roughness played an
important role in providing effective surface for bone implant contact, cell
proliferation, and removal torque, despite having good mechanical properties.
Overall, published studies indicated that an acid etched surface-modified and a
coating application on commercial pure titanium implant was most preferable in
producing the good surface roughness. Thus, a combination of a good surface
roughness and mechanical properties of titanium could lead to successful dental
implants.
PMID- 26436098
TI - Ultrastructural Morphology of Sperm from Human Globozoospermia.
AB - Globozoospermia is a rare disorder characterized by the presence of sperm with
round head, lacking acrosome. Coiling tail around the nucleus has been reported
since early human studies, but no specific significance has conferred it. By
contrast, studies on animal models suggest that coiling tail around the nucleus
could represent a crucial step of defective spermatogenesis, resulting in round
headed sperm. No observations, so far, support the transfer of this hypothesis to
human globozoospermia. The purpose of this work was to compare ultrastructural
morphology of human and mouse model globozoospermic sperm. Sperm have been
investigated by using scanning and transmission electron microscopy. The images
that we obtained show significant similarities to those described in GOPC
knockout mice, an animal model of globozoospermia. By using this model as
reference, we were able to identify the probable steps of the tail coiling
process in human globozoospermia. Although we have no evidence that there is the
same pathophysiology in man and knocked-out mouse, the similarities between these
ultrastructural observations in human and those in the experimental model are
very suggestive. This is the first demonstration of the existence of relevant
morphological homologies between the tail coiling in animal model and human
globozoospermia.
PMID- 26436099
TI - Anodisation Increases Integration of Unloaded Titanium Implants in Sheep
Mandible.
AB - Spark discharge anodic oxidation forms porous TiO2 films on titanium implant
surfaces. This increases surface roughness and concentration of calcium and
phosphate ions and may enhance early osseointegration. To test this, forty 3.75
mm * 13 mm titanium implants (Megagen, Korea) were placed into healed mandibular
postextraction ridges of 10 sheep. There were 10 implants per group: RBM surface
(control), RBM + anodised, RBM + anodised + fluoride, and titanium alloy +
anodised surface. Resonant frequency analysis (RFA) was measured in implant
stability quotient (ISQ) at surgery and at sacrifice after 1-month unloaded
healing. Mean bone-implant contact (% BIC) was measured in undemineralised ground
sections for the best three consecutive threads. One of 40 implants showed
evidence of failure. RFA differed between groups at surgery but not after 1
month. RFA values increased nonsignificantly for all implants after 1 month,
except for controls. There was a marked difference in BIC after 1-month healing,
with higher values for alloy implants, followed by anodised + fluoride and
anodised implants. Anodisation increased early osseointegration of rough-surfaced
implants by 50-80%. RFA testing lacked sufficient resolution to detect this
improvement. Whether this gain in early bone-implant contact is clinically
significant is the subject of future experiments.
PMID- 26436102
TI - Utility and limitations of animal models for the functional validation of human
sequence variants.
PMID- 26436103
TI - Medical genetics and genomic medicine in Greece: achievements and challenges.
PMID- 26436100
TI - In Vitro Selection of Cancer Cell-Specific Molecular Recognition Elements from
Amino Acid Libraries.
AB - Differential cell systematic evolution of ligands by exponential enrichment
(SELEX) is an in vitro selection method for obtaining molecular recognition
elements (MREs) that specifically bind to individual cell types with high
affinity. MREs are selected from initial large libraries of different nucleic or
amino acids. This review outlines the construction of peptide and antibody
fragment libraries as well as their different host types. Common methods of
selection are also reviewed. Additionally, examples of cancer cell MREs are
discussed, as well as their potential applications.
PMID- 26436101
TI - The Clinical Relevance of IL-17-Producing CD4+CD161+ Cell and Its Subpopulations
in Primary Sjogren's Syndrome.
AB - OBJECTIVE: Th17 cells have been demonstrated to play an important role in the
onset and development of primary Sjogren's syndrome (pSS). In this study, we
evaluated the expansion and clinical significance of circulating CD4+CD161+ T
cell and its "effector" (CD4+CD25-CD161+ T cell) and "regulatory"
(CD4+CD25+CD161+ T cell) subpopulations. METHODS: Fifty-eight pSS patients and 16
healthy controls (HCs) were recruited in our study. The cell populations and
intracellular IL-17 expression were analyzed by flow cytometry. The disease
activity was evaluated by the EULAR-SS Disease Activity Index (ESSDAI).
Autoantibodies were measured by ELISA or indirect immunofluorescence assay.
RESULTS: The CD161+ T cell fractions showed higher proportions of IL-17-producing
cells. The frequencies of the overall CD4+CD161+ T cell population and its
effector subset were positively correlated with disease activity parameters and
more severe disease manifestations. A significant elevation of the
CD4+CD25+CD161+ T cell subpopulation was observed in the peripheral blood of pSS
patients compared to HCs and this subset showed decreased regulatory functions
compared with the CD4+CD25+CD161- population. CONCLUSION: Circulating CD4+CD161+
T cell populations associated with pSS disease activity and severity. These cells
might be involved in the development of pSS and could be potential therapeutic
targets in the treatment of pSS.
PMID- 26436104
TI - Familial adenomatous polyposis in an adolescent with coexisting schizophrenia:
treatment strategies and implications.
AB - Schizophrenia is associated with high mortality and morbidity. The etiology of
schizophrenia remains unclear, studies implicate a multifactorial origin with
genetic and environmental factors. The adenomatous polyposis coli (APC) gene has
been associated with FAP (familial adenomatous polyposis), and studies have
linked it to schizophrenia. However, there are few studies which examine the
association between FAP and schizophrenia. Limited data exist regarding
recommendations for genetic counseling of adolescents with comorbid psychiatric
illness. A case of an adolescent with FAP who developed psychotic symptoms is
presented. This case hopes to add to the literature about mental illness in those
with FAP. A review of literature about the role of APC in schizophrenia as well
as implications of genetic counseling on those who suffer with mental illness
will be discussed.
PMID- 26436105
TI - Validation of a semiconductor next-generation sequencing assay for the clinical
genetic screening of CFTR.
AB - Genetic testing for cystic fibrosis and CFTR-related disorders mostly relies on
laborious molecular tools that use Sanger sequencing to scan for mutations in the
CFTR gene. We have explored a more efficient genetic screening strategy based on
next-generation sequencing (NGS) of the CFTR gene. We validated this approach in
a cohort of 177 patients with previously known CFTR mutations and polymorphisms.
Genomic DNA was amplified using the Ion AmpliSeqTM CFTR panel. The DNA libraries
were pooled, barcoded, and sequenced using an Ion Torrent PGM sequencer. The
combination of different robust bioinformatics tools allowed us to detect
previously known pathogenic mutations and polymorphisms in the 177 samples,
without detecting spurious pathogenic calls. In summary, the assay achieves a
sensitivity of 94.45% (95% CI: 92% to 96.9%), with a specificity of detecting
nonvariant sites from the CFTR reference sequence of 100% (95% CI: 100% to 100%),
a positive predictive value of 100% (95% CI: 100% to 100%), and a negative
predictive value of 99.99% (95% CI: 99.99% to 100%). In addition, we describe the
observed allelic frequencies of 94 unique definitely and likely pathogenic,
uncertain, and neutral CFTR variants, some of them not previously annotated in
the public databases. Strikingly, a seven exon spanning deletion as well as
several more technically challenging variants such as pathogenic poly-thymidine
guanine and poly-thymidine (poly-TG-T) tracts were also detected. Targeted NGS is
ready to substitute classical molecular methods to perform genetic testing on the
CFTR gene.
PMID- 26436106
TI - Novel recruitment strategy to enrich for LRRK2 mutation carriers.
AB - The LRRK2 G2019S mutation is found at higher frequency among Parkinson disease
(PD) patients of Ashkenazi Jewish (AJ) ancestry. This study was designed to test
whether an internet-based approach could be an effective approach to screen and
identify mutation carriers. Individuals with and without PD of AJ ancestry were
recruited and consented through an internet-based study website. An algorithm was
applied to a series of screening questions to identify individuals at increased
risk to carry the LRRK2 G2019S mutation. About 1000 individuals completed the
initial screening. Around 741 qualified for mutation testing and 650 were tested.
Seventy-two individuals carried at least one LRRK2 G2019S mutation; 38 with PD
(12.5%) and 34 without (10.1%). Among the AJ PD participants, each affected first
degree relative increased the likelihood the individual was LRRK2+ [OR = 4.7; 95%
confidence interval = (2.4-9.0)]. The same was not observed among the unaffected
AJ subjects (P = 0.11). An internet-based approach successfully screened large
numbers of individuals to identify those with risk factors increasing the
likelihood that they carried a LRRK2 G2019S mutation. A similar approach could be
implemented in other disorders to identify individuals for clinical trials,
biomarker analyses and other types of research studies.
PMID- 26436107
TI - Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome
presenting with skeletal malformation and malignant lymphoproliferative disease.
AB - Glycosaminoglycans (GAGs) such as chondroitin are ubiquitous disaccharide
carbohydrate chains that contribute to the formation and function of
proteoglycans at the cell membrane and in the extracellular matrix. Although GAG
modifying enzymes are required for diverse cellular functions, the role of these
proteins in human development and disease is less well understood. Here, we
describe two sisters out of seven siblings affected by congenital limb
malformation and malignant lymphoproliferative disease. Using Whole-Genome
Sequencing (WGS), we identified in the proband deletion of a 55 kb region within
chromosome 12q23 that encompasses part of CHST11 (encoding chondroitin-4
sulfotransferase 1) and an embedded microRNA (MIR3922). The deletion was
homozygous in the proband but not in each of three unaffected siblings.
Genotyping data from the 1000 Genomes Project suggest that deletions inclusive of
both CHST11 and MIR3922 are rare events. Given that CHST11 deficiency causes
severe chondrodysplasia in mice that is similar to human limb malformation, these
results underscore the importance of chondroitin modification in normal skeletal
development. Our findings also potentially reveal an unexpected role for CHST11
and/or MIR3922 as tumor suppressors whose disruption may contribute to malignant
lymphoproliferative disease.
PMID- 26436108
TI - Limb body wall complex, amniotic band sequence, or new syndrome caused by
mutation in IQ Motif containing K (IQCK)?
AB - Limb body wall complex (LBWC) and amniotic band sequence (ABS) are multiple
congenital anomaly conditions with craniofacial, limb, and ventral wall defects.
LBWC and ABS are considered separate entities by some, and a continuum of
severity of the same condition by others. The etiology of LBWC/ABS remains
unknown and multiple hypotheses have been proposed. One individual with features
of LBWC and his unaffected parents were whole exome sequenced and Sanger
sequenced as confirmation of the mutation. Functional studies were conducted
using morpholino knockdown studies followed by human mRNA rescue experiments.
Using whole exome sequencing, a de novo heterozygous mutation was found in the
gene IQCK: c.667C>G; p.Q223E and confirmed by Sanger sequencing in an individual
with LBWC. Morpholino knockdown of iqck mRNA in the zebrafish showed ventral
defects including failure of ventral fin to develop and cardiac edema. Human wild
type IQCK mRNA rescued the zebrafish phenotype, whereas human p.Q223E IQCK mRNA
did not, but worsened the phenotype of the morpholino knockdown zebrafish. This
study supports a genetic etiology for LBWC/ABS, or potentially a new syndrome.
PMID- 26436109
TI - Actionable clinical decisions based on comprehensive genomic evaluation in
asymptomatic adults.
AB - Whole-exome sequencing (WES) arises as a new approach in diagnosing individuals
affected by multigenic and complex phenotypes. Herein, we aim to examine whether
WES is useful in screening asymptomatic individuals for actionable interventions,
which has not yet been established. Twenty-five healthy adults underwent WES,
bioinformatics, and manual curation of their exomes. Six participants (24%)
harbored significant, management-changing variants in cancer predisposition
genes, American College of Medical Genetics, and genomics reportable cardiac
diseases and pharmacogenomic biomarkers that have led to clinical recommendations
and interventions. Furthermore, more than 80% of the participants (21) carried 1
3 genetic variants with an associated clinical guideline for an altered drug
dosing or administration based on the FDA's table of pharmacogenomics. These
results support WES potential not only to answer specific diagnostic questions
presented by the relevant personal and/or family history but also to uncover
clinically important genetic findings unrelated to the primary indication for
sequencing.
PMID- 26436110
TI - Regulatory variant in FZD6 gene contributes to nonsyndromic cleft lip and palate
in an African-American family.
AB - Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth
defect affecting 135,000 newborns worldwide each year. While a multifactorial
etiology has been suggested as the cause, despite decades of research, the
genetic underpinnings of NSCLP remain largely unexplained. In our previous genome
wide linkage study of a large NSCLP African-American family, we identified a
candidate locus at 8q21.3-24.12 (LOD = 2.98). This region contained four genes,
Frizzled-6 (FZD6), Matrilin-2 (MATN2), Odd-skipped related 2 (OSR2) and Solute
Carrier Family 25, Member 32 (SLC25A32). FZD6 was located under the maximum
linkage peak. In this study, we sequenced the coding and noncoding regions of
these genes in two affected family members, and identified a rare variant in
intron 1 of FZD6 (rs138557689; c.-153 + 432A>C). The variant C allele segregated
with NSCLP in this family, through affected and unaffected individuals, and was
found in one other NSCLP African-American family. Functional assays showed that
this allele creates an allele-specific protein-binding site and decreases
promoter activity. We also observed that loss and gain of fzd6 in zebrafish
contributes to craniofacial anomalies. FZD6 regulates the WNT signaling pathway,
which is involved in craniofacial development, including midfacial formation and
upper labial fusion. We hypothesize, therefore, that alteration in FZD6
expression contributes to NSCLP in this family by perturbing the WNT signaling
pathway.
PMID- 26436111
TI - EGFR mutations cause a lethal syndrome of epithelial dysfunction with progeroid
features.
AB - The epidermal growth factor receptor (EGFR) is part of a large family of
receptors required for communicating extracellular signals through internal
tyrosine kinases. Epidermal growth factor (EGF) signaling is required for tissue
development, whereas constitutive activation of this signaling pathway is
associated with oncogenic transformation. We identified homozygous c.1283G>A
(p.Gly428Asp) mutations in the extracellular domain of EGFR in two siblings. The
children were born prematurely, had abnormalities in skin and hair, suffered
multisystem organ failure, and died in the neonatal period from intestinal
perforation. EGF failed to induce mutated receptor phosphorylation in patient
derived fibroblasts and activation of downstream targets was suppressed. The
heterologously expressed extracellular domain was impaired in stability and the
binding of EGF. Cells from the affected patient undergo early senescence with
accelerated expression of beta-galactosidase and shortened telomeres at all
passages when compared to controls. A comparison of homozygous inherited regions
from a separate report of a patient from the same ethnic background and EGFR
genotype confirms the pathogenicity of EGFR mutations in congenital disease.
PMID- 26436112
TI - Multigene panel analysis identified germline mutations of DNA repair genes in
breast and ovarian cancer.
AB - Approximately 5-10% of all breast and/or ovarian cancer cases are considered as
inherited. BRCA1 and BRCA2 tumor suppressor genes account for a high penetrance
of hereditary cases, but familial cases without mutations in these genes can also
occur. Despite their low penetrance, other hereditary cancer-related genes are
known to be associated with breast and ovarian cancer risk. However, the extent
to which these genes prevail in breast and ovarian cancer remains to be
elucidated. To estimate the frequency of mutations in these predisposition genes,
we analyzed the germline mutations of 25 hereditary cancer-related genes in 155
patients using targeted next-generation sequencing. These subjects included 11
BRCA1/2 mutation-positive cases and 144 negative cases. Of these, three patients
(1.9%) had pathogenic mutations in ATM, MRE11A, or MSH6, all of which have a
central role in DNA repair and the mismatch repair pathway. The MSH6 splice-site
mutation (IVS6+1G>T) was predicted to be pathogenic, as demonstrated by in vitro
and immunohistochemical analyses. These results suggested deficiencies in
cellular DNA repair functions result in the development of breast and ovarian
cancer.
PMID- 26436113
TI - Mutations in CDK5RAP2 cause Seckel syndrome.
AB - Seckel syndrome is a heterogeneous, autosomal recessive disorder marked by
prenatal proportionate short stature, severe microcephaly, intellectual
disability, and characteristic facial features. Here, we describe the novel
homozygous splice-site mutations c.383+1G>C and c.4005-9A>G in CDK5RAP2 in two
consanguineous families with Seckel syndrome. CDK5RAP2 (CEP215) encodes a
centrosomal protein which is known to be essential for centrosomal cohesion and
proper spindle formation and has been shown to be causally involved in autosomal
recessive primary microcephaly. We establish CDK5RAP2 as a disease-causing gene
for Seckel syndrome and show that loss of functional CDK5RAP2 leads to severe
defects in mitosis and spindle organization, resulting in cells with abnormal
nuclei and centrosomal pattern, which underlines the important role of
centrosomal and mitotic proteins in the pathogenesis of the disease.
Additionally, we present an intriguing case of possible digenic inheritance in
Seckel syndrome: A severely affected child of nonconsanguineous German parents
was found to carry heterozygous mutations in CDK5RAP2 and CEP152. This finding
points toward a potential additive genetic effect of mutations in CDK5RAP2 and
CEP152.
PMID- 26436114
TI - Communicating with School Staff About Sexual Identity, Health and Safety: An
Exploratory Study of the Experiences and Preferences of Black and Latino Teen
Young Men Who Have Sex with Men.
AB - PURPOSE: This exploratory study examined the experiences of black and Latino teen
young men who have sex with men (YMSM) and their preferences for communication
with school staff about matters related to sexual orientation. METHODS:
Participants for this study were recruited in three urban centers in the United
States and by multiple community-based organizations serving black and Latino
YMSM. Eligible youth were male, black and Latino, ages 13-19, enrolled in 90 days
of school in the previous 18 months, and reported attraction to or sexual
behavior with other males, or identified as gay or bisexual. Participants
completed web-based questionnaires (n=415) and/or in-depth interviews (n=32).
RESULTS: Questionnaire participants reported willingness to talk to at least one
school staff member about: safety, dating and relationships, and feeling
attracted to other guys (63.4%, 58.4%, and 55.9%, respectively). About one-third
of the sample reported they would not talk with any school staff about these
topics. Exploratory analyses revealed youth who experienced feeling unsafe at
school and who had higher levels of trust in the information provided by school
staff were more likely to be willing to talk with school staff about safety
issues, dating, or same sex attraction (adjusted odds ratio [AOR]=2.80 and
AOR=4.85, respectively). Interview participants reported being most willing to
talk to staff who were able and willing to help them, who would keep discussions
confidential, and who expressed genuine care. Preferences for confiding in school
staff perceived to be lesbian, gay, bisexual, and transgender (LGBT) and having
similar racial/ethnic background were also noted. CONCLUSION: Findings suggest
school staff can serve as points of contact for reaching YMSM and professional
development and interventions can be tailored to reach YMSM and connect them to
services they need. Additional research is needed to understand how to increase
YMSM comfort talking with school staff about sexual health or sexual identity
concerns.
PMID- 26436115
TI - Hepatitis B virus infection: An insight into infection outcomes and recent
treatment options.
AB - Hepatitis B virus (HBV) currently infects an estimated population of 2 billion
individuals in the world, including 400 million people with chronic HBV
infection. HBV virology, replication and the host's immune response to HBV
infection contribute to different infection outcomes. Acute hepatitis HBV
infection is self-limiting but it leaves a residual infection that can become
active in an individual during immunosuppression. In chronic HBV infection, the
virus persistently replicates in hepatocytes leading to immune mediated
hepatocellular damage. Despite the inability to remove the virus in more than 70
% of patients, current treatments for chronic HBV infection, interferon alpha and
antiviral nucleotide/nucleoside analogues, aim to reduce viral replication to
prevent or at least delay the progression to cirrhosis and hepatocellular
carcinoma. In both self resolved acute and persistent HBV infection, the long
term existence of chromatinised covalently closed circular DNA (cccDNA) in the
nuclei of infected hepatocytes cannot be targeted by current treatments to
eliminate these templates to eradicate the viral persistence. Identifying the
mechanisms involve in the removal of infected hepatocytes will be useful as
treatment options. In this context, DNA based novel therapeutic and immunization
strategies might help to remove stable cccDNA and thus viral persistence.
PMID- 26436116
TI - Gene expression profiling in gill tissues of White spot syndrome virus infected
black tiger shrimp Penaeus monodon by DNA microarray.
AB - White spot syndrome virus (WSSV) continues to be the most devastating viral
pathogen infecting penaeid shrimp the world over. The genome of WSSV has been
deciphered and characterized from three geographical isolates and significant
progress has been made in developing various molecular diagnostic methods to
detect the virus. However, the information on host immune gene response to WSSV
pathogenesis is limited. Microarray analysis was carried out as an approach to
analyse the gene expression in black tiger shrimp Penaeus monodon in response to
WSSV infection. Gill tissues collected from the WSSV infected shrimp at 6, 24, 48
h and moribund stage were analysed for differential gene expression. Shrimp cDNAs
of 40,059 unique sequences were considered for designing the microarray chip. The
Cy3-labeled cRNA derived from healthy and WSSV-infected shrimp was subjected to
hybridization with all the DNA spots in the microarray which revealed 8,633 and
11,147 as up- and down-regulated genes respectively at different time intervals
post infection. The altered expression of these numerous genes represented
diverse functions such as immune response, osmoregulation, apoptosis, nucleic
acid binding, energy and metabolism, signal transduction, stress response and
molting. The changes in gene expression profiles observed by microarray analysis
provides molecular insights and framework of genes which are up- and down
regulated at different time intervals during WSSV infection in shrimp. The
microarray data was validated by Real Time analysis of four differentially
expressed genes involved in apoptosis (translationally controlled tumor protein,
inhibitor of apoptosis protein, ubiquitin conjugated enzyme E2 and caspase) for
gene expression levels. The role of apoptosis related genes in WSSV infected
shrimp is discussed herein.
PMID- 26436117
TI - Evaluation of thermo-stability of bluetongue virus recombinant VP7 antigen in
indirect ELISA.
AB - This study shows the thermo-stability of lyophilized and purified recombinant VP7
bluetongue virus (BTV) protein in the presence of two sugar stabilizers
(trehalose and mannitol) at different temperature. Truncated VP7 protein purified
by nickel affinity column was lyophilized in the presence of trehalose and
mannitol at 60 mM final concentration and then exposed to different temperature
like 4, 25, 37 and 45 degrees C for various periods like 5 months, 7 weeks, 7
days and 48 h, respectively. After thermal treatment, the reactivity of the
protein was evaluated in indirect ELISA. At 4 and 25 degrees C, the protein was
stable up to 5 months and 7 weeks, respectively, irrespective of stabilizers
used. At 37 degrees C, it was stable up to 3 days with both the stabilizers,
after which it lost its stability and reactivity. At 45 degrees C, the protein
was stable up to 30 and 24 h with trehalose and mannitol stabilizers,
respectively. Both stabilizers found suitable for stability of the protein.
However, trehalose appeared to have better stabilizing effect, particularly at
higher temperatures than the mannitol. Trehalose could be used as stabilizer for
freeze-drying the recombinant VP7 protein if an indirect ELISA kit based on the
purified rVP7 protein is supplied to different laboratories of the country for
detection of BTV antibody in sheep.
PMID- 26436118
TI - In-silico structural analysis of the influenza A subtype H7N9 neuraminidase and
molecular docking with different neuraminidase inhibitors.
AB - Human infection with H7 influenza subtypes usually resulted in mild disease with
a rare mortalities, however, human infection with the avian low pathogenic H7N9
influenza virus resulted in about 38.6 % human fatality. Due to the new cross
species barrier of this virus subtype, there is an urgent need to better
understand the susceptibility to commercially available antivirals and their
relation to the structural changes of the viral neuraminidase. Neuraminidases
derived from 2013 H7N9, H5N1 and H1N1 were subjected to a structural analysis of
their catalytic and framework binding sites. The modeling structure of selected
neuraminidases from H7N9 and influenza A subtypes were solved and the docking
studies with oseltamivir, zanamivir, laninamivir and peramivir were conducted.
The active site residues that are responsible for both binding and cleavage of
the terminally linked sialic acid receptors were found conserved. Docking studies
with oseltamivir, zanamivir, laninamivir and peramivir revealed that the
laninamivir and peramivir showed superior energy binding activities in comparison
to the commonly used oseltamivir and zanamivir. The results presented in the
current study provide data that are useful for the future treatment of different
influenza A subtypes including the recently emerged H7N9.
PMID- 26436119
TI - First genome analysis and molecular characterization of Chickpea chlorotic dwarf
virus Egyptian isolate infecting squash.
AB - This study aims to identifying and characterizing some molecular properties of
geminiviruses co-infection in squash field crop cultivated in Egypt. Squash crops
observed to be heavily infected with several insect vectors, also severe
chlorosis and stunting was observed. Electron microscopic analysis has revealed
geminate capsid particles which indicate the infection of Geminiviruses,
especially SqLCV which represent an economic problem to squash filed crop in
Egypt. We have investigated possible mixed infections with different plant
viruses associated with chlorotic stunt diseases and or other genus groups of
geminiviruses. The main objective of this study is to investigate the
recombination events, possible recombinants and variants among these genera in
the same family differing in vector transmission. This is the first report of the
molecular characterization, phylogenetic analysis and putative recombination
events of the full length genome of the Chickpea Chlorotic Dwarf Mastrevirus in
Egypt. And the first report of co-infection with another begomovirus infecting
squash plants. A full length clone of both viruses were isolated and
characterized at the molecular level. The complete nucleotide sequence of DNA-A
was determined (2,572 bp) and submitted to the genbank under accession no.
KF692356. The isolate from Egypt has about 97.8 % homology with the Chickpea
chlorotic dwarf virus (CpCDV) isolate from Syria DNA-A isolate FR687959, a 83.2 %
homology with the Sudan isolate AM933134 and a 82.7 % homology with Pakistan
isolate FR687960. To best of our knowledge this is the first report of complete
genome of CpCDV that infect squash plants in Egypt and worldwide.
PMID- 26436120
TI - Isolation and molecular characterization of nephropathic infectious bronchitis
virus isolates of Gujarat state, India.
AB - Infectious bronchitis (IB) is a common, highly contagious, acute, and
economically important viral disease of chickens caused by Infectious bronchitis
virus (IBV, sp. Avian coronavirus). Five pooled tissue suspensions of 50 layer
birds and one reference Massachusetts vaccine strain were inoculated into
specific pathogen free (SPF) chicken egg for isolation of IBV. Reverse
transcription polymerase chain reaction (RT-PCR) was carried out using post
inoculated allontoic fluid to amplify the spike (S) glycoprotein of S1 subunit of
IBV. All the eggs inoculated with five pooled tissue samples and vaccine sample
showed dwarfing and curling of SPF embryos indicative of IBV. All the five
samples and the vaccine sample produced the expected amplicons of 466 bp by RT
PCR. The sequencing of five isolates revealed that all the five sequences were
99.09-100 % similar among themselves and showed 99.10-100 % nucleotide identity
with the vaccine strain. On multiple sequence alignment it was found that our
isolates were more similar at S1 subunit nucleotide level with the reference Ma5
and H120 vaccine strains than the reference Mass41 strain. The sequences of Anand
isolates revealed further genetic changes in the circulating IBV in comparison to
previous isolate of Gujarat as well as higher differences with the strains
isolated in other states showing substantial changes at genetic level in Indian
IBV isolates, which may partially explain the increasing incidences of IB in the
country in spite of the vaccination.
PMID- 26436121
TI - Heterozygosity at the SNP (rs136500299) of ITGB6 receptor gene possibly
influences the susceptibility among crossbred bull to foot and mouth disease
infection.
AB - Zebu (Bos indicus) cattle are known to be resistant against foot and mouth
disease virus (FMDV) compared to taurine (Bos taurus). To understand the
susceptibility of two cattle species to FMDV infection in terms of viral
receptors, the present study reports the cloning, characterization and sequence
analysis of Zebu ITGB6 gene. The complete CDS of zebu ITGB6 was 2367 basepair in
length with 788 amino acid residues. The zebu integrin shares common structural
and functional elements with taurine and other species. We identified an amino
substitution (S665 to F665) presents in ITGB6 gene among zebu and taurine as SNP
(rs136500299). Further, we determined and compared the structural differences of
ITGB6 receptor gene among zebu and taurine species. To elucidate the influence of
the SNP on the susceptibility of cattle to FMDV infection, a tetra ARMS PCR based
genetic screening was performed among Zebu and crossbred cattle. Our observation
revealed that, the targeted SNP are strongly (P < 0.05) associated with FMD
susceptibility among Frieswal (HF X Sahiwal) crossbred cattle.
PMID- 26436122
TI - Transgenic tobacco plants expressing siRNA targeted against the Mungbean yellow
mosaic virus transcriptional activator protein gene efficiently block the viral
DNA accumulation.
AB - Mungbean yellow mosaic virus (MYMV) is a bipartite begomovirus that infects many
pulse crops such as blackgram, mungbean, mothbean, Frenchbean, and soybean. We
tested the efficacy of the transgenically expressed intron-spliced hairpin RNA
gene of the transcriptional activator protein (hpTrAP) in reducing MYMV DNA
accumulation. Tobacco plants transformed with the MYMV hpTrAP gene accumulated 21
22 nt siRNA. Leaf discs of the transgenic plants, agroinoculated with the partial
dimers of MYMV, displayed pronounced reduction in MYMV DNA accumulation. Thus,
silencing of the TrAP gene, a suppressor of gene silencing, emerged as an
effective strategy to control MYMV.
PMID- 26436123
TI - Modulation of gene expression in CD4+ T lymphocytes following in vitro HIV
infection: a comparison between human and chimpanzee.
AB - Chimpanzees are susceptible to experimental infection by human deficiency virus
(HIV)-1, but unlike humans, they exceptionally develop an immunodeficiency
syndrome after HIV-1 inoculation. To explore the difference between human and
chimpanzee, we analyzed the expression of 1547 genes of various functions in
human or chimpanzee CD4+ lymphoblasts inoculated in vitro with HIV-1. We observed
that, 1 day after HIV inoculation, fifty-eight genes were up-regulated in
lymphoblasts of the three humans while their expression remained unchanged in
lymphoblasts of the three chimpanzees. One gene is involved in adhesion of HIV
(catenin-alpha), three in the immune response (semaphorin 4D, placental growth
factor, IL-6), three in apoptosis (deleted in colorectal carcinoma, caspase 9 and
FOXO1A). No difference between species was revealed for the expression of 373
genes related to glycosylation pathways. The in vitro human/chimpanzee comparison
reveals new candidate genes up-regulated after inoculation with HIV-1 only in
human lymphoblasts and which could be related to the higher sensitivity of human
to HIV-induced AIDS.
PMID- 26436124
TI - Characterization of cytopathogenicity of classical swine fever virus isolate
induced by Newcastle disease virus.
AB - Classical swine fever virus (CSFV), the causative agent of classical swine fever,
belongs to the family Flaviviridae and genus Pestivirus. Some pestiviruses
exhibit cytopathic effect in cell culture but exact phenomenon is unknown. Over
expression of NS2-3 gene, presence of defective interfering particle and
exaltation of Newcastle disease virus (END) phenomenon could be the reasons of
cytopathogenicity. In the present study, a CSFV isolate exhibiting cytopathic
effect (CPE) in Madin-Darby Canine Kidney (MDCK) cell line was characterized. To
characterize cytopathogenicity of such isolate, END test was carried out.
Interference of Newcastle disease virus (NDV) in MDCK adapted CSFV was confirmed
by RT-PCR and virus neutralization test. Absence of CPE and NDV specific nucleic
acid after neutralization confirmed the induction of CPE by NDV. Further,
identity of the CSFV isolate in MDCK cell line by immunoperoxidase test,
immunoblotting and RT-PCR post NDV neutralization established the virus
replication without CPE (non-cytopathic isolate). Findings suggest that, there
could be a chance of mixed infection of both CSFV and NDV in the piglet from
which the sample was collected for virus isolation.
PMID- 26436125
TI - Lower respiratory tract infections among HIV positive and control group in Nepal.
AB - Lower respiratory tract infections (LRTIs) are the most frequent respiratory
diseases among HIV infected patients and are frequently the first clinical
manifestations of the HIV infections. LRTIs are common not only among the HIV
seropositive cases but also the commonest domiciliary and nosocomial infections
among the general population. The present study was carried out to determine the
comparative prevalence of common bacterial and fungal organism among the HIV
positive and control population. This cross sectional study was conducted among
220 people attending National Public Health Laboratory, Kathmandu, Nepal. Out of
them 120 were HIV sero-positive and rest were HIV sero-negative. Sputum samples
were collected and processed soon after its collection. Macroscopic examination
was done to determine the sample integrity. Gram stain, AFB stain and KOH
preparation was performed for preliminary identification of the pathogens.
Culture was carried out for bacterial and fungal pathogens. Antibiotic
susceptibility test (Kirby-Bauer disc diffusion method) was performed from the
isolated organisms. The 85 out of 120 HIV sero-positive patients were found to be
infected with one or more microbial pathogens. The overall infection rate was
found to be significantly lower in HIV seronegative people (27 %). Among HIV
seropositive cases prevalence of LRTIs was strongly associated with lower CD4
counts (<200/mm(3)). The prevalence of mycobacterium tuberculosis was found to be
10 % among HIV/AIDS patients which was significantly higher than among the non
HIV cases (3 %). The bacterial pathogens was observed among 46.6 % of HIV
positive and 22.0 % of HIV negative people. Among the positive cases, K.
pneumoniae was the predominant bacterial pathogens, followed by E. coli and S.
pneumoniae. C. albicans was found to be predominant fungal pathogen followed by
Aspergillus spp. germ tube negative Candida spp. and Penicillium spp. Similar
types of organisms were found to be associated with LRTIs among HIV positive and
negative people. The prevalence of both fungal and bacterial infections was
significantly higher among HIV seropositive people than HIV seronegative people.
All in all, lower respiratory tract illness is significantly higher in HIV/AIDS
cases than in HIV seronegative cases.
PMID- 26436126
TI - Isolation and molecular characterization of Orf virus from natural outbreaks in
goats of Assam.
AB - Outbreaks of contagious ecthyma (caused by a Parapox virus) in goats were
investigated in 6 districts of Assam, a north eastern state of India. Diagnosis
of the disease was carried out employing both standard virological as well as
molecular methods. Four representative isolates from different places were
selected for phylogenetic analysis. The major envelop protein (B2L) of Orf virus
was targeted for molecular analysis. The sequencing and phylogenetic analysis of
the selected sequences at nucleotide level revealed that the Orf virus isolates
were closely related to each other (97.6-100 %) and showed highest similarity to
the Orf virus isolate 82/04 (98.4 %), reported from Shahjahanpur, India. The data
will provide an insight in transmission of the virus from northern to North
eastern part of the country.
PMID- 26436127
TI - Safety of inoculation of bovine parainfluenza virus 3 as potential vaccine vector
in pigs.
AB - Bovine parainfluenza virus 3 (BPIV3) is one of the most important respiratory
pathogens in cattle. One BPIV3, named NM09, was isolated from cattle suffering
from severe respiratory diseases in 2009. BPIV3 is a potential recombinant
vaccine vector. To investigate whether NM09 can infect pigs and determine BPIV3
defense in these animals, BPIV3 antibody-free pigs were inoculated
intramuscularly with the BPIV3 NM09 strain in a continuous passage. Clinical
signs were observed each day after inoculation. Viral nucleic acid was detected
in nasal and anal secretions. Results showed that virus-inoculated pigs displayed
few observable clinical signs related to respiratory diseases. The antibody was
identified, but the virus could not be detected in the second continuous passage
in pigs. Thus, BPIV3 is a potential vaccine vector for genetic engineering.
PMID- 26436128
TI - Malus pumila 'Spy 227' and Apple stem pitting virus: graft incompatibility and
epinasty.
AB - Apple stem pitting foveavirus (ASPV) is one of the most important and widespread
virus infecting apples in the world. Of late, the virus has been found to be
invariably associated with most of the apple plantations of Shimla district of
Himachal Pradesh based on DAS-ELISA results. Bioassay of viruses in vegetatively
propagated crops including apple is considered to be an essential component in
indexing programmes for the production of virus free propagating material. Woody
indicator Malus pumila 'Spy 227' was used for the detection of ASPV through
double grafting method. Graft incompatibility and epinasty symptoms were observed
on Malus pumila Spy 227 indicator plants. Further, molecular identification of
the virus isolate was done by cloning and sequencing of the test isolate. Partial
sequence analysis of the coat protein gene showed 89 % nucleotide identity in
BLASTN analysis with ASPV isolate from China (Accession No. JF895517). This is
the first record of ASPV producing Graft incompatibility on Spy 227 indicator
plants.
PMID- 26436129
TI - Ionising radiation and risk of death from leukaemia and lymphoma in radiation
monitored workers (INWORKS): an international cohort study.
AB - BACKGROUND: There is much uncertainty about the risks of leukaemia and lymphoma
after repeated or protracted low-dose radiation exposure typical of occupational,
environmental, and diagnostic medical settings. We quantified associations
between protracted low-dose radiation exposures and leukaemia, lymphoma, and
multiple myeloma mortality among radiation-monitored adults employed in France,
the UK, and the USA. METHODS: We assembled a cohort of 308,297 radiation
monitored workers employed for at least 1 year by the Atomic Energy Commission,
AREVA Nuclear Cycle, or the National Electricity Company in France, the
Departments of Energy and Defence in the USA, and nuclear industry employers
included in the National Registry for Radiation Workers in the UK. The cohort was
followed up for a total of 8.22 million person-years. We ascertained deaths
caused by leukaemia, lymphoma, and multiple myeloma. We used Poisson regression
to quantify associations between estimated red bone marrow absorbed dose and
leukaemia and lymphoma mortality. FINDINGS: Doses were accrued at very low rates
(mean 1.1 mGy per year, SD 2.6). The excess relative risk of leukaemia mortality
(excluding chronic lymphocytic leukaemia) was 2.96 per Gy (90% CI 1.17-5.21;
lagged 2 years), most notably because of an association between radiation dose
and mortality from chronic myeloid leukaemia (excess relative risk per Gy 10.45,
90% CI 4.48-19.65). INTERPRETATION: This study provides strong evidence of
positive associations between protracted low-dose radiation exposure and
leukaemia. FUNDING: Centers for Disease Control and Prevention, Ministry of
Health, Labour and Welfare of Japan, Institut de Radioprotection et de Surete
Nucleaire, AREVA, Electricite de France, National Institute for Occupational
Safety and Health, US Department of Energy, US Department of Health and Human
Services, University of North Carolina, Public Health England.
PMID- 26436131
TI - Examining Racial/Ethnic Disparities in the Association between Adolescent Sleep
and Alcohol or Marijuana Use.
AB - OBJECTIVES: The current study examines the association between self-reported
measures of trouble sleeping, total sleep time (TST), and bedtimes and odds of
past month alcohol and marijuana (AM) use in a racially/ethnically diverse sample
of adolescents. DESIGN: Web-based cross-sectional survey. SETTING: Los Angeles
(LA) County, California. PARTICIPANTS: The sample is comprised of 2539 youth
representing four distinct racial/ethnic categories (Non-Hispanic White,
Hispanic, Asian, and "Other"; mean age= 15.54; 54.23% female) from Los Angeles.
MEASUREMENTS: The survey assessed TST and bedtimes (weekdays and weekends),
trouble sleeping, and past month AM use, as well as relevant covariates
(sociodemographics and mental health symptoms). RESULTS: Although there were
significant racial/ethnic differences in the prevalence of sleep problems and AM
use, the associations between sleep problems and AM use were consistent across
racial/ethnic groups. Specifically, shorter TST, later bedtimes, and trouble
sleeping, were each associated with significantly higher odds of past month
alcohol use, whereas later bedtimes and shorter TST were also associated with
increased odds of past month marijuana use, even after adjusting for other known
risk factors. CONCLUSIONS: Sleep problems are associated with increased AM use in
teens, even after controlling for sociodemographics and mental health symptoms.
Further longitudinal research on sleep and AM use is critical to identify novel
prevention and intervention efforts to reduce disparities in the relationship
between sleep and AM use.
PMID- 26436130
TI - Ponatinib as first-line treatment for patients with chronic myeloid leukaemia in
chronic phase: a phase 2 study.
AB - BACKGROUND: Ponatinib has shown efficacy in patients with refractory chronic
myeloid leukaemia (CML) and in those with CML with a Thr315Ile mutation. We aimed
to investigate the activity and safety of ponatinib as first-line treatment for
patients with chronic-phase CML. METHODS: We did a single-arm, phase 2 trial at
MD Anderson Cancer Center in Houston, TX, USA. Between May 3, 2012, and Sept 24,
2013, we enrolled patients with early (<6 months) chronic-phase CML and treated
them with oral ponatinib once a day. Patients enrolled before July 25, 2013, were
given a starting dose of 45 mg per day; we lowered this due to tolerability
issues and patients enrolled after this date were given a starting dose of 30 mg
per day. After a warning by the US Food and Drug Administration (FDA) in Oct 6,
2013, for vascular complications with ponatinib, we started all patients on
aspirin 81 mg daily and reduced the dose of ponatinib to 30 mg or 15 mg per day
for all patients. The primary endpoint was the proportion of patients who
achieved complete cytogenetic response by 6 months in the per-protocol
population. This trial is registered with ClinicalTrials.gov, number NCT01570868.
FINDINGS: We enrolled 51 patients. Median follow-up was 20.9 months (IQR 14.9
25.2). 43 patients were started on 45 mg ponatinib every day; eight patients were
started on 30 mg per day. 43 (94%) of 46 evaluable patients achieved complete
cytogenetic response at 6 months. Most frequent toxicities included skin-related
effects (n=35; 69%) and elevated lipase (n=32; 63%). Cardiovascular events
(mainly hypertension) occurred in 25 (49%) patients. Grade 3-4 myelosuppression
occurred in 15 (29%) patients. Five (10%) patients developed cerebrovascular or
vaso-occlusive disease. 43 (85%) patients needed treatment interruptions at some
time and 45 (88%) needed dose reductions. The study was terminated June 18, 2014,
at the recommendation of the FDA due to concern about the increased risk of
thromboembolism with ponatinib. INTERPRETATION: Patients with newly diagnosed CML
in chronic phase respond well to treatment with ponatinib, with most achieving a
complete cytogenetic response. Dose adjustment, extensive monitoring, and
counselling of the patients for thromboembolic events is needed for patients on
ponatinib therapy. However, due to the risk of vascular thrombotic events and the
availability of alternative options for these patients, other drugs should be
considered first in the frontline setting. FUNDING: MD Anderson Cancer Center,
National Cancer Institute, ARIAD Pharmaceutical.
PMID- 26436132
TI - Novel Strategy to Improve the Performance of Localization in WSN.
AB - A novel strategy of discrete energy consumption model for WSN based on quasi
Monte Carlo and crude Monte Carlo method is developed. In our model the discrete
hidden Markov process plays a major role in analyzing the node location in
heterogeneous media. In this energy consumption model we use both static and
dynamic sensor nodes to monitor the optimized energy of all sensor nodes in which
every sensor state can be considered as the dynamic Bayesian network. By using
this method the power is assigned in terms of dynamic manner to each sensor over
discrete time steps to control the graphical structure of our network. The
simulation and experiment result shows that our proposed methods are better in
terms of localization accuracy and possess minimum computational time over
existing localization method.
PMID- 26436133
TI - NADPH Oxidases in Chronic Liver Diseases.
AB - Oxidative stress is a common feature observed in a wide spectrum of chronic liver
diseases including viral hepatitis, alcoholic, and nonalcoholic steatohepatitis.
The nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are
emerging as major sources of reactive oxygen species (ROS). Several major
isoforms are expressed in the liver, including NOX1, NOX2, and NOX4. While the
phagocytic NOX2 has been known to play an important role in Kupffer cell and
neutrophil phagocytic activity and inflammation, the nonphagocytic NOX homologues
are increasingly recognized as key enzymes in oxidative injury and wound healing.
In this review, we will summarize the current advances in knowledge on the
regulatory pathways of NOX activation, their cellular distribution, and their
role in the modulation of redox signaling in liver diseases.
PMID- 26436136
TI - Recruitment and Retention of Smokers Versus Nonsmokers in an rTMS Study.
AB - Repetitive transcranial magnetic stimulation (rTMS) is a new frontier in the
examination of addictive behaviors and perhaps the development of new
interventions. This study examined differences in recruitment, eligibility, and
retention among smokers and nonsmokers in an rTMS study. We modeled participant
eligibility and study completion among eligible participants accounting for
demographic differences between smokers and nonsmokers. Nonsmokers were more
likely than smokers to remain eligible for the study after the in-person screen
(84.2% versus 57.4%; OR 4.0 CI: 1.0, 15.4, p=0.05) and to complete the study
(87.5% versus 59.3%; OR=43.9 CI: 2.8, 687.2, p=0.007). The preliminary findings
suggest that careful screening for drugs of abuse and brain abnormalities among
smokers prior to administering rTMS is warranted. More research is needed
concerning the prevalence of brain abnormalities in smokers. Smokers might need
to be informed about a higher risk of incidental MRI findings.
PMID- 26436134
TI - Pediatric cancer gone viral. Part II: potential clinical application of oncolytic
herpes simplex virus-1 in children.
AB - Oncolytic engineered herpes simplex viruses (HSVs) possess many biologic and
functional attributes that support their use in clinical trials in children with
solid tumors. Tumor cells, in an effort to escape regulatory mechanisms that
would impair their growth and progression, have removed many mechanisms that
would have protected them from virus infection and eventual virus-mediated
destruction. Viruses engineered to exploit this weakness, like mutant HSV, can be
safely employed as tumor cell killers, since normal cells retain these antiviral
strategies. Many preclinical studies and early phase trials in adults
demonstrated that oncolytic HSV can be safely used and are highly effective in
killing tumor cells that comprise pediatric malignancies, without generating the
toxic side effects of nondiscriminatory chemotherapy or radiation therapy. A
variety of engineered viruses have been developed and tested in numerous
preclinical models of pediatric cancers and initial trials in patients are
underway. In Part II of this review series, we examine the preclinical evidence
to support the further advancement of oncolytic HSV in the pediatric population.
We discuss clinical advances made to date in this emerging era of oncolytic
virotherapy.
PMID- 26436135
TI - Pediatric cancer gone viral. Part I: strategies for utilizing oncolytic herpes
simplex virus-1 in children.
AB - Progress for improving outcomes in pediatric patients with solid tumors remains
slow. In addition, currently available therapies are fraught with numerous side
effects, often causing significant life-long morbidity for long-term survivors.
The use of viruses to kill tumor cells based on their increased vulnerability to
infection is gaining traction, with several viruses moving through early and
advanced phase clinical testing. The prospect of increased efficacy and decreased
toxicity with these agents is thus attractive for pediatric cancer. In part I of
this two-part review, we focus on strategies for utilizing oncolytic engineered
herpes simplex virus (HSV) to target pediatric malignancies. We discuss
mechanisms of action, routes of delivery, and the role of preexisting immunity on
antitumor efficacy. Challenges to maximizing oncolytic HSV in children are
examined, and we highlight how these may be overcome through various arming
strategies. We review the preclinical and clinical evidence demonstrating safety
of a variety of oncolytic HSVs. In Part II, we focus on the antitumor efficacy of
oncolytic HSV in pediatric tumor types, pediatric clinical advances made to date,
and future prospects for utilizing HSV in pediatric patients with solid tumors.
PMID- 26436137
TI - Partial Saturation of Menaquinone in Mycobacterium tuberculosis: Function and
Essentiality of a Novel Reductase, MenJ.
AB - Menaquinone (MK) with partially saturated isoprenyl moieties is found in a wide
range of eubacteria and Archaea. In many Gram-positive organisms, including
mycobacteria, it is the double bond found in the beta-isoprene unit that is
reduced. Mass spectral characterization of menaquinone from mycobacterial
knockout strains and heterologous expression hosts demonstrates that Rv0561c
(designated menJ) encodes an enzyme which reduces the beta-isoprene unit of
menaquinone in Mycobacterium tuberculosis, forming the predominant form of
menaquinone found in mycobacteria. MenJ is highly conserved in mycobacteria
species but is not required for growth in culture. Disruption of menJ reduces
mycobacterial electron transport efficiency by 3-fold, but mycobacteria are able
to maintain ATP levels by increasing the levels of the total menaquinone in the
membrane; however, MenJ is required for M. tuberculosis survival in host
macrophages. Thus, MK with partially hydrogenated isoprenyl moieties represents a
novel virulence factor and MenJ is a contextually essential enzyme and a
potential drug target in pathogenic mycobacteria and other Gram-positive
pathogens.
PMID- 26436138
TI - Structure-Based Design of Dendritic Peptide Bolaamphiphiles for siRNA Delivery.
AB - Development of safe and effective delivery vectors is a critical challenge for
the application of RNA interference (RNAi)-based biotechnologies. In this study
we show the rational design of a series of novel dendritic peptide bolaamphiphile
vectors that demonstrate high efficiency for the delivery of small interfering
RNA (siRNA) while exhibiting low cytotoxicity and hemolytic activity. Systematic
investigation into structure-property relationships revealed an important
correlation between molecular design, self-assembled nanostructure, and
biological activity. The unique bolaamphiphile architecture proved a key factor
for improved complex stability and transfection efficiency. The optimal vector
contains a fluorocarbon core and exhibited enhanced delivery efficiency to a
variety of cell lines and improved serum resistance when compared to hydrocarbon
analogues and lipofectamine RNAiMAX. In addition to introducing a promising new
vector system for siRNA delivery, the structure-property relationships and
"fluorocarbon effect" revealed herein offer critical insight for further
development of novel materials for nucleic acid delivery and other biomaterial
applications.
PMID- 26436139
TI - Assessing Systemic Stress in Otolaryngology: Methodology and Feasibility of Hair
and Salivary Cortisol Testing.
AB - OBJECTIVE: Elevated systemic stress is a predictor of adverse health outcomes,
and stress can be objectively quantified by cortisol concentration. Despite its
utility, such testing is rarely performed in otolaryngology. This manuscript
provides details on the principles, methodology, and feasibility of performing
laboratory assessments of hair and salivary cortisol to inform researchers
wishing to incorporate these novel tests in future otolaryngologic studies.
METHODS: Participants were older adults with hearing impairment. One hair sample
and eight saliva samples were collected. Feasibility of study design was assessed
through rates of participation in hair and saliva sampling and protocol adherence
for saliva collection. Area under the curve (AUC) was used to evaluate overall
secretion, and cortisol awakening response (CAR) was used to evaluate the dynamic
secretion response. RESULTS: From 9/1/2013 to 12/31/2013, 26/30 (86.7%) eligible
participants agreed to hair sampling. All 30 subjects agreed to collect saliva,
with 29 (96.7%) adhering to the collection protocol. Mean AUC was 401.2 nmol/L
per hour, and CAR was 4.5 nmol/L. CONCLUSIONS: Evaluating systemic stress in an
otolaryngologic population using hair and saliva is feasible with acceptable
participation and adherence. Repeat measurements over time will allow for
evaluation of changes in systemic stress in relation to treatment.
PMID- 26436140
TI - Entropy-scaling search of massive biological data.
AB - Many data sets exhibit well-defined structure that can be exploited to design
faster search tools, but it is not always clear when such acceleration is
possible. Here we introduce a framework for similarity search based on
characterizing a data set's entropy and fractal dimension. We prove that
searching scales in time with metric entropy (number of covering hyperspheres),
if the fractal dimension of the data set is low, and scales in space with the sum
of metric entropy and information-theoretic entropy (randomness of the data).
Using these ideas, we present accelerated versions of standard tools, with no
loss in specificity and little loss in sensitivity, for use in three domains-high
throughput drug screening (Ammolite, 150x speedup), metagenomics (MICA, 3.5x
speedup of DIAMOND (3700x BLASTX)), and protein structure search (esFragBag, 10x
speedup of FragBag). Our framework can be used to achieve 'compressive omics,'
and the general theory can be readily applied to data science problems outside of
biology. Source code: http://gems.csail.mit.edu.
PMID- 26436141
TI - Brevetoxin Degradation and By-Product Formation via Natural Sunlight.
AB - We investigated the effects of solar radiation on brevetoxin (PbTx2). Our
findings suggest that natural sunlight mediates brevetoxin (PbTx2) degradation
and results in brevetoxin by-product formation via photochemical processes.
PMID- 26436142
TI - Competitive ELISA: An Accurate, Quick and Effective Tool to Monitor Brevetoxins
in Environmental and Biological Sample.
AB - A competitive Enzyme-Linked Immuno-Sorbent Assay (competitive ELISA) has been
developed for analyzing brevetoxins (PbTxs). Antibodies to brevetoxins were used
in combination with a multi-step signal amplification procedure for the detection
of toxins. This procedure minimizes non-specific signals and background noise
often observed in complex matrices. Therefore, analysis can be performed with
various samples (seawater, air filter, mammalian body fluids, shellfish, etc.)
without the need for extensive extraction and/or purification steps. Brevetoxin
analysis in liquid samples like seawater, urine and serum can be performed
without pretreatment, dilution or purification. The limit of quantification of
PbTxs is 2 ng mL-1 in any of the liquid sample matrices tested. For shellfish
monitoring, analyses are performed after homogenization of shellfish meat (5 g)
with brevetoxin-ELISA buffer (200 mL) and can be performed on tissue from a
single mollusk as well as on a pool of shellfish meat. Comparative quantification
of PbTxs achieved in buffer, seawater, mammalian body fluid and shellfish
homogenate spiked with equal amounts of toxin (10 ng mL-1 sample) varied by no
more than 5%. These data suggest that the matrix composition of the sample does
not affect the performance of the assay. Because this assay is not affected by
matrix composition and can be performed in shellfish homogenate, this procedure
can be used to prevent or diagnose human exposure to PbTxs and has the potential
to replace the currently used mouse bioassay for monitoring PbTxs in shellfish.
PMID- 26436143
TI - Multi-Laboratory Study of Five Methods for the Determination of Brevetoxins in
Shellfish Tissue Extracts.
AB - A thirteen-laboratory comparative study tested the performance of four methods as
alternatives to mouse bioassay for the determination of brevetoxins in shellfish.
The methods were N2a neuroblastoma cell assay, two variations of the sodium
channel receptor binding assay, competitive ELISA, and LC/MS. Three to five
laboratories independently performed each method using centrally prepared spiked
and naturally incurred test samples. Competitive ELISA and receptor binding (96
well format) compared most favorably with mouse bioassay. Between-laboratory
relative standard deviations (RSDR) ranged from 10 to 20% for ELISA and 14 to 31%
for receptor binding. Within-laboratory (RSDr) ranged from 6 to 15% for ELISA,
and 5 to 31% for receptor binding. Cell assay was extremely sensitive but data
variation rendered it unsuitable for statistical treatment. LC/MS performed as
well as ELISA on spiked test samples but was inordinately affected by lack of
toxin-metabolite standards, uniform instrumental parameters, or both, on incurred
test samples. The ELISA and receptor binding assay are good alternatives to mouse
bioassay for the determination of brevetoxins in shellfish.
PMID- 26436144
TI - Florida Red Tide: Inhalation Toxicity of Karenia brevis Extract in Rats.
AB - Brevetoxins are neurotoxins produced by the marine dinoflagellate Karenia brevis.
Histopathologic examination of marine mammals dying following repeated exposure
of brevetoxins during red tide events suggests that the respiratory tract,
nervous, hematopoietic, and immune systems are potential targets for toxicity in
repeatedly exposed individuals. The purpose of this experiment was to evaluate
the effects of repeated inhalation of K. brevis extract on these potential target
systems in rats. Male Sprague-Dawley rats were exposed four hours/day, five
days/week for up to four weeks to target concentrations of 200 and 1000 MUg/L K.
brevis extract (approximately 50 and 200 MUg/L brevetoxin-like compounds;
positive neurotoxicity in a fish bioassay). Control rats were sham exposed to
air. Immunohistochemical staining of pulmonary macrophages indicated deposition
of brevetoxin-like compound within the lung. However, exposure resulted in no
clinical signs of toxicity or behavioral changes. There were no adverse effects
on hematology or serum chemistry. No histopathological changes were observed in
the nose, lung, liver, kidneys, lymph nodes, spleen, or brain of exposed rats.
Immune suppression was suggested by reduced responses of spleen cells in the IgM
specific antibody-forming plaque cell response assay and reduced responses of
lymphocytes to mitogen stimulation in vitro. Differences between responses
observed in rats in this study and those observed in manatees may be a function
of dose or species differences in sensitivity.
PMID- 26436145
TI - An Epidemiologic Approach to the Study of Aerosolized Florida Red Tides.
AB - Very little has been published in the scientific literature on the human health
effects of Florida red tide, either as human clinical case reports or formal
epidemiologic studies. In addition to the health effects associated with the
ingestion of contaminated shellfish, there have been multiple anecdotal reports
of respiratory irritation and possible immunologic effects associated with the
inhalation of aerosolized Florida red tide. To investigate the human health
effects from environmental exposure to red tide toxins, we have formed an
interdisciplinary team of scientists. We have created a network of public and
environmental health workers who periodically report local conditions as a red
tide develops. In addition, we have access to environmental monitoring data as
well as data from a surveillance program supported through the Florida Poison
Information Network. When a red tide moves onshore where people might be exposed,
the team rapidly assembles at the site to collect environmental samples and
epidemiologic data. To assess the more long-term effects from environmental
exposure to red tide toxins, we are conducting epidemiologic studies involving
occupational and sensitive populations who live in areas that are regularly
impacted by red tides. Other scientists are evaluating the acute and chronic
respiratory effects of red tides and brevetoxins in both rat and sheep models as
well as refinement of toxin measurement methodology. These models are being used
to refine and validate the biomarkers of brevetoxins exposure as well as explore
the pathophysiology of health effects from brevetoxins respiratory exposure.
Bolstered by the additional research in rat and sheep models, this
interdisciplinary scientific team is exploring the acute and chronic exposures
and health effects of aerosolized Florida red tides in animal models and various
human populations. In the future, this research can be applied to the
understanding of exposure and effects of other aerosolized natural toxins such as
cyanobacterial toxins.
PMID- 26436146
TI - Fenton reaction-mediated fluorescence quenching of N-acetyl-L-cysteine-protected
gold nanoclusters: analytical applications of hydrogen peroxide, glucose, and
catalase detection.
AB - Given the importance of hydrogen peroxide (H2O2) in many biological processes and
its wide application in various industries, the demand for sensitive, accurate,
and economical H2O2 sensors is high. In this study, we used Fenton reaction
stimulated fluorescence quenching of N-acetyl-L-cysteine-protected gold
nanoclusters (NAC-AuNCs) as a reporter system for the determination of H2O2.
After the experimental conditions were optimized, the sensing platform enabled
the analysis of H2O2 with a limit of detection (LOD) as low as 0.027 MUM. As the
glucose oxidase cascade leads to the generation of H2O2 and catalase catalyzes
the decomposition of H2O2, these two biocatalytic procedures can be probed by the
Fenton reaction-mediated quenching of NAC-AuNCs. The LOD for glucose was found to
be 0.18 MUM, and the linear range was 0.39-27.22 MUM. The LOD for catalase was
0.002 U mL(-1), and the linear range was 0.01-0.3 U mL(-1). Moreover, the
proposed sensing methods were successfully applied for human serum glucose
detection and the non-invasive determination of catalase activity in human
saliva, demonstrating their great potential for practical applications.
PMID- 26436147
TI - Rapid and efficient pesticide detection via cyclodextrin-promoted energy
transfer.
AB - Cyclodextrins facilitate non-covalent fluorescence energy transfer from a variety
of pesticides to high quantum-yield fluorophores, resulting in a rapid, sensitive
detection scheme for these compounds with detection limits as low as two
micromolar. Such a facile detection tool has significant potential applications
in agriculture and public health research.
PMID- 26436148
TI - Cross-linked supramolecular polymer metallogels constructed via a self-sorting
strategy and their multiple stimulus-response behaviors.
AB - Novel cross-linked supramolecular polymer metallogels were successfully
constructed from four components via a self-sorting strategy, and feature
interesting multiple stimulus-response behaviors under various external stimuli,
including halide, base, and competitive guests.
PMID- 26436149
TI - A high stiffness bio-inspired hydrogel from the combination of a poly(amido
amine) dendrimer with DOPA.
AB - A robust biodegradable hydrogel is constructed from two components containing
G4.0 PAMAM and DOPA, which displays excellent interconnected porous 3D networks,
higher mechanical strength, low and stable swelling and good biocompatibility. A
mouse CSD model in vivo evidences that moderate bone-like tissue and extensive
bony tissue are observed when the hydrogel is implanted.
PMID- 26436150
TI - Retractions.
PMID- 26436151
TI - Preface: Selected papers from the 30th SEGH Conference on Environmental
Geochemistry and Health.
PMID- 26436152
TI - Reflections: neurology and the humanities: Clarity.
PMID- 26436153
TI - Long sleep duration in elders without dementia increases risk of dementia
mortality (NEDICES).
PMID- 26436154
TI - Author response.
PMID- 26436155
TI - Commentary on "Pregnancy week at delivery and the risk of shoulder dystocia: A
population study of 2,014,956 deliveries".
PMID- 26436156
TI - Editorial: big data for health.
PMID- 26436158
TI - Predictive modeling in health informatics.
PMID- 26436157
TI - EMBC 2014.
PMID- 26436159
TI - Unobtrusive assessment of the mechanical aspects of cardiovascular function.
PMID- 26436160
TI - Corticosteroids: out of fashion?
PMID- 26436161
TI - Rituximab (MABTHERA) and severe polyangiitis. An option for patients informed of
the uncertainties.
AB - Granulomatosis with polyangiitis (Wegener's granulomatosis) and microscopic
polyangiitis are two types of rapidly fatal necrotizing vasculitis. The standard
induction therapy consists of cyclophosphamide (an immunosuppressant) plus a
corticosteroid. This treatment significantly prolongs survival but has burdensome
adverse effects. After an induction phase lasting 3 to 6 months, cyclophosphamide
is replaced by another immunosuppressant such as azathioprine for 2 to 5 years in
order to prevent relapse. There is no consensus on an alternative treatment for
patients who cannot receive cyclophosphamide. Rituximab, a monoclonal antibody
already approved in oncology and rheumatology, is now authorised in the European
Union for induction therapy in adult patients with granulomatosis with
polyangiitis and microscopic polyangiitis. A randomised, double-blind, non
inferiority trial in 197 patients compared intravenous rituximab infusion once a
week for 4 weeks, versus oral cyclophosphamide given for 3 to 6 months, followed
by azathioprine for 12 months. During the 18-month follow-up period, 2% of
patients in each group died. Rituximab was at least as effective as
cyclophosphamide in terms of complete remission rate by 6 months (primary
endpoint), which was respectively 64% and 55%. At 18 months, about one-third of
patients in both arms were still in remission, despite the absence of maintenance
therapy in the rituximab arm. Uncertainties concerning the use of rituximab in
this setting include its longer-term impact on survival, possible advantage in
patients who relapse, efficacy in patients with life-threatening disease, and
optimal dose. During 18 months of follow-up, about 42% of patients in the
rituximab group and 70% of those in the cyclophosphamide and azathioprine group
had at least one treatment-related adverse effect. The following adverse effects
were more frequent with rituximab than with sequential treatment with
cyclophosphamide followed by azathioprine: infections, thrombocytopenia,
diarrhoea, peripheral oedema, cough and cardiovascular disorders, while the
following effects were more frequent with cyclophosphamide followed by
azathioprine: leukopenia, venous thromboembolism, nausea, vomiting, transaminase
elevation and hair loss. Rituximab should be avoided during pregnancy because it
can cause lymphopenia in the unborn child. Its effects on fertility are poorly
documented. In practice, in patients with severe granulomatosis with polyangiitis
or microscopic polyangiitis, rituximab is as effective at 18 months as
cyclophosphamide followed by azathioprine; in addition, it has different and less
frequent adverse effects. Rituximab is therefore an alternative when the standard
treatment is likely to be problematic, but patients should be informed that
longer-term efficacy is uncertain and that the optimal dose remains to be
established.
PMID- 26436162
TI - INN COMMON STEM: -tide.
PMID- 26436164
TI - Ranibizumab(Lucentis) in high myopia with neovascularization. Better short-term
visual acuity but serious adverse effects.
AB - In a trial versus verteporfin photodynamic therapy, ranibizumab improved visual
acuity after 3 months of treatment but had more adverse effects.
PMID- 26436165
TI - Dabigatran (Pradaxa): deep vein thrombosis and pulmonary embolism. Warfarin
remains the standard drug.
AB - Not more effective than warfarin in three "non-inferiority" trials. Less bleeding
but more acute coronary events with dabigatran, and still no antidote.
PMID- 26436166
TI - omalizumab (Xolair) and chronic spontaneous urticaria. Too many adverse effects
and uncertainties.
AB - Omalizumab has only modest and transient symptomatic efficacy when an
antihistamine is ineffective. Its adverse effects can be severe, and its safety
during long-term use is uncertain. Omalizumab is not better than a
corticosteroid.
PMID- 26436167
TI - Febuxostat (Adenuric). Toxic epidermal necrolysis and severe hypersensitivity
reactions added to the EU SPC.
AB - This hypouricaemic drug does not have a better adverse effect profile than
allopurinol.
PMID- 26436168
TI - Methylphenidate: pulmonary hypertension and heart valve disease.
AB - Several amphetamine-like appetite suppressants are known to have cardiovascular
adverse effects, in particular pulmonary arterial hypertension and cardiac valve
disease. Is this also the case with methylphenidate, an amphetamine-like
psychostimulant used in attention-deficit hyperactivity disorder (especially in
children) and also in narcolepsy? Cases of pulmonary hypertension and heart valve
disease have been reported with methylphenidate, including in children. The risk
appears to be low, but epidemiological studies are needed to estimate the
incidence. This risk should be minimised by only using methylphenidate to treat
serious disorders, at the lowest effective dose. Attention should be paid to
warning signs such as dyspnoea.
PMID- 26436169
TI - Mechanisms of action of amphetamine-like drugs.
PMID- 26436170
TI - Red yeast rice: muscle and liver disorders.
PMID- 26436171
TI - Hydroxychloroquine: hypoglycaemia.
PMID- 26436172
TI - Efavirenz: suicides.
PMID- 26436173
TI - Smoking cessation during pregnancy.
PMID- 26436174
TI - Epicondylitis and corticosteroid injection: fewer cures at one year.
AB - Corticosteroid injection provides short-term relief for patients with
epicondylitis. However, in a trial lasting one year, corticosteroid injection
resulted in a lower complete recovery rate and higher recurrence rate.
Physiotherapy appears to improve symptoms in the short-term without affecting
outcome at one year.
PMID- 26436175
TI - How INNs are created. Making drug names safer by contributing to INN selection.
AB - The international nonproprietary names (INNs) of drugs proposed by the World
Health Organization (WHO) are released for public consultation. These
consultations provide an opportunity to identify any risks associated with INNs
that could lead to confusion. Prescrire has submitted numerous comments since it
began participating in the WHO's public consultations on proposed INNs in 2007.
The WHO INN programme has occasionally taken our objections into account. It is
easier to replace a proposed INN when a risk of confusion is identified early,
before the drug is introduced to the market and the INN enters into use. Regular
analysis of the INNs proposed by the WHO reveals some of the challenges of naming
drugs and the influence exerted by pharmaceutical companies and the US drug
nomenclature committee (USANC) in particular. The lack of an identifiable common
stem in certain INNs, sometimes perceived as an obstacle to INN
comprehensibility, is a consequence of the procedure for assigning INNs, because
the INN programme wants to ensure that new common stems are not created
prematurely. Critical analysis of proposed INNs during WHO public consultations
offers an insight into the challenges involved in devising common stems. This
analysis is useful for improving the quality and safety of INNs.
PMID- 26436176
TI - The finances of Association Mieux Prescrire: 2014 Prescrire annual report.
PMID- 26436177
TI - For the Future.
PMID- 26436178
TI - The Advantage of a General Journal.
PMID- 26436179
TI - Results From Wisconsin Medical Society's Physician Satisfaction Survey Are Cause
for Concern.
PMID- 26436180
TI - Dissatisfaction Among Wisconsin Physicians Is Part of Serious National Trend.
PMID- 26436181
TI - Factors Affecting Physician Satisfaction and Wisconsin Medical Society Strategies
to Drive Change.
AB - Physicians' dissatisfaction in their work is increasing, which is affecting the
stability of health care in America. The Wisconsin Medical Society (Society)
surveyed 1016 Wisconsin physicians to determine the source of their
dissatisfaction. The survey results indicate Wisconsin physicians are satisfied
when it comes to practice environment, work-life balance, and income. In
addition, they are extremely satisfied when it comes to rating their ability to
provide high quality care, and they have identified some benefits related to the
adoption of electronic health records. However, they are feeling burned out, very
unsatisfied with the amount of time spent in direct patient care compared to
indirect patient care, and that they are spending too much time on administrative
and data entry tasks. In terms of future workforce, many physicians are either
unsure or would not recommend the profession to a prospective medical student.
Electronic health records serve as both a satisfier and dissatisfier and as a
potential driver for future physician satisfaction interventions. Changes at the
institutional, organizational, and individual levels potentially could address
the identified dissatisfiers and build upon the satisfiers. The Society
identifies 12 strategies to improve upon the physician experience.
PMID- 26436183
TI - Assessment of Food Insecurity in Children's Hospital of Wisconsin's Emergency
Department.
AB - IMPORTANCE: Food insecurity is associated with adverse health outcomes and the
emergency department may be an ideal location to identify food insecure children
and families. OBJECTIVE: To determine the prevalence of food insecurity in
families with children that present to an urban pediatric emergency department
(ED) in Milwaukee, Wisconsin. DESIGN: We conducted a cross-sectional survey of
caregivers of children 0-18 years between June and August, 2013. The
questionnaire included 2 validated statements about food insecurity and
demographic and community resource questions. Participant rooms were approached
during predefined shifts in an order determined by random number generation.
OUTCOMES: The primary outcome was the prevalence of caregivers who identified as
food insecure. A secondary outcome was the percentage of food insecure caregivers
who accessed community resources. RESULTS: We enrolled 309 caregivers; 141
(45.6%) reported food insecurity. Nearly 60% (56.8%) of nonwhite caregivers were
food insecure compared to 27.4% of non-Hispanic white caregivers (P < 0.0001).
Among caregivers who identified as food insecure, 82% reported using at least 1
community resource for food. CONCLUSIONS: Almost half of caregivers presenting to
the ED reported food insecurity. The ED is an excellent location for targeted
intervention to identify and link food insecure families with community
resources.
PMID- 26436182
TI - Association Between Alcohol Use Among College Students and Alcohol Outlet
Proximity and Densities.
AB - BACKGROUND: Alcohol consumption is common on college campuses and is associated
with negative consequences. Factors associated with availability of alcohol are
not completely understood. OBJECTIVE: To describe how proximity and density of
alcohol outlets are associated with any drinking and binge drinking in students
at the University of Wisconsin-Madison. METHODS: Participants were full-time
students enrolled in the Young Adults Eating and Active for Health, a multisite,
randomized intervention that assessed a variety of health behaviors. Geographic
information systems were used to calculate proximity and enumerate alcohol outlet
densities. Participants were categorized as "drinkers" or "nondrinkers" based on
self-reported alcohol consumption. Binge drinking was categorized as "non-binge
drinker," "frequent binge drinker," and "excessive binge drinker." Analysis
included regression, t tests, and chi-square tests. RESULTS. Among the 166
participants, 126 (76%) were drinkers. Among drinkers, 80 (63%) were either
frequent or excessive binge drinkers. Drinkers lived closer to an alcohol outlet
than non-drinkers (0.18 +/- 0.15 vs. 0.61 +/- 1.59 miles, respectively, P=0.005).
Within a 1-mile walking radius, there were 47% more establishments for drinkers
(153 +/- 47 compared to 104 +/- 55 outlets for nondrinkers, P<0.0001). At
distances of 0.10-0.25 and 0.25-0.50 miles, twice as many outlets were available
to drinkers (19 +/- 19 and 43 +/- 25, respectively) compared to nondrinkers (7 +/
11 and 20 +/- 22, respectively), P<0.001. Proximity and density were hot
associated with binge drinking frequency. CONCLUSION: Drinkers lived closer to
alcohol outlets and had significantly more outlets available at a distance of up
to 1 mile. Municipal and college administrators could consider limiting alcohol
license distributions in municipalities with high alcohol consumption.
PMID- 26436184
TI - The Emergence of Clinically Relevant Babesiosis in Southwestern Wisconsin.
AB - OBJECTIVE: To determine the frequency and characteristics of babesiosis cases,
and to assess the impact of the introduction of a tick-borne infection diagnostic
panel on babesiosis diagnosis in the region surrounding La Crosse, Wisconsin,
where babesiosis in non-travelers was previously rare. METHODS: In the spring of
2013, we conducted a point-in-time survey of Ixodes scopuloris ticks for the
presence of Babesia microti. We also conducted a retrospective study of all
babesiosis cases diagnosed in our health system between January 1, 2004, and
November 1, 2013. Finally, we compared the number of babesiosis cases diagnosed
during the study period before and after the June 1, 2012, introduction of a tick
borne infection diagnostic panel in our organization. RESULTS: Babesia microti
was present in 5% of ticks surveyed in our region. Twenty-two cases. of
babesiosis were diagnosed in our organization during the study period-19 since
2010. The tick-borne infection diagnostic panel was used widely by clinicians,
with an attendant increase in babesiosis diagnoses. CONCLUSION: Babesiosis should
be considered endemic in southwestern Wisconsin, and testing should be considered
for patients with compatible clinical and laboratory features.
PMID- 26436185
TI - The Savant Syndrome Registry: A Preliminary Report.
AB - A registry has been established to document certain characteristics on a sizeable
worldwide sample of individuals with savant syndrome, a rare but remarkable
condition in which persons with developmental disabilities, brain injury, or
brain disease have some spectacular "islands" of skill or ability that stand in
jarring, marked contrast to overall handicap. Of the 319 savants included in the
registry, 90% are congenital savants, while 10% are acquired savants. The
registry includes individuals from 33 countries, with 70% from the United States
or Canada. Sex distribution was 79% male vs. 21% female (4:1). This report
summarizes the findings in the congenital savant syndrome category of the
registry. Among the individuals with congenital savant syndrome, the most common
underlying disability was Autistic Spectrum Disorder (75%); various other central
nervous system (CNS) disorders were present in the other 25%. Fifty-five percent
possessed a single special skill, while 45% had multiple skills. Music was the
most frequent principal skill followed by art, memory, mathematics, calendar
calculating, language, visual-spatial/mechanical, athletic, computer,
extrasensory perception, and other skills.
PMID- 26436186
TI - Hypocalcemia Secondary to Zoledronate Therapy in a Patient With Low Vitamin D
Level.
AB - Zoledronate (ZDA) is a bisphosphonate used to treat hypercalcemia that commonly
occurs with malignancy, multiple myeloma, and bone metastases from solid tumors.
It acts primarily by decreasing osteoclastic activity, thereby slowing the
release of skeletal calcium. However, a potential adverse effect of ZDA is
hypocalcemia that can be symptomatic, especially in patients with risk factors
such as hypomagnesemia, hypoparathyroidism, renal failure, and vitamin D
deficiency. We report the case of a patient with extensive stage small cell lung
cancer with multiple osseous and visceral metastases who developed symptomatic
hypocalcemia following ZDA administration. Significant clinical improvement
occurred following administration of calcium and vitamin D, and his calcium
levels returned to normal within a few days. Due to the high incidence of vitamin
D deficiency and the low accuracy of clinical risk factors to predict vitamin D
deficiency, screening for vitamin D deficiency before administration of ZDA may
be appropriate.
PMID- 26436187
TI - Medical Training in the Fitbit, Google Glass and Personal Information Era.
PMID- 26436188
TI - Implementing Heart Health Strategies With Point-of Care and Population
Management.
PMID- 26436189
TI - ANMF priorities. What's in store for 2015.
PMID- 26436190
TI - Curriculum in unis needed to protect students from violence.
PMID- 26436191
TI - Scope of practice and cancer care.
PMID- 26436193
TI - Cancer mapped out globally.
PMID- 26436192
TI - Rotating night shift increases risk of disease.
PMID- 26436194
TI - Nurses' role essential at end-of-life.
PMID- 26436195
TI - Incidental exercises could save lives.
PMID- 26436196
TI - Heart condition twice as common in Indigenous Australians.
PMID- 26436198
TI - Exploration of new functional endpoints in neuro-2a cells for the detection of
the marine biotoxins saxitoxin, palytoxin and tetrodotoxin.
AB - Marine neurotoxins accumulate in seafood and therewith represent a threat for
consumers. At the European level, the use of in vivo bioassays is banned from
2015 onwards, except for the control of production areas. Cytotoxicity in the
neuro-2a assay has been shown a promising in vitro alternative. However, given
that cytotoxicity may be sensitive to confounding factors the current study
investigates the suitability of functional endpoints as alternatives to
cytotoxicity for the detection of marine neurotoxins. Microarray analyses were
performed following exposure of neuro-2a cells to three marine neurotoxins
(palytoxin (PlTx), saxitoxin (STX) and tetrodotoxin (TTX)) to identify genes up-
or down-regulated that can be used as biomarkers for screening purposes. In
addition to microarrays, the voltage dependent fluorescent probe bisoxonol was
used to assess changes in cellular membrane potential. Biomarkers based on mRNA
expression were detected for PlTx but not for STX and TTX. STX and TTX decreased
the fluorescence of bisoxonol while PlTx showed no effect. When using
cytotoxicity as the read out the neuro-2a assay detects these three neurotoxins
at similar concentrations. Therefore it is concluded that the newly investigated
endpoints in the neuro-2a assay are not preferred over cytotoxicity in a suitable
broad and sensitive bioassay for the detection of marine neurotoxins in real
practice.
PMID- 26436199
TI - Lead-Free Piezoceramics: Revealing the Role of the Rhombohedral-Tetragonal Phase
Coexistence in Enhancement of the Piezoelectric Properties.
AB - Until now, lead zirconate titanate (PZT) based ceramics are the most widely used
in piezoelectric devices. However, the use of lead is being avoided due to its
toxicity and environmental risks. Indeed, the attention in piezoelectric devices
has been moved to lead-free ceramics, especially on (K,Na)NbO3-based materials,
due to growing environmental concerns. Here we report a systematic evaluation of
the effects of the compositional modifications induced by replacement of the B
sites with Sb(5+) ions in 0.96[(K0.48Na0.52)0.95Li0.05Nb1-xSbxO3]-0.04[BaZrO3]
lead-free piezoceramics. We show that this compositional design is the driving
force for the development of the high piezoelectric properties. So, we find that
this phenomenon can be explained by the stabilization of a Rhombohedral
Tetragonal (R-T) phase boundary close to room temperature, that facilities the
polarization process of the system and exhibits a significantly high
piezoelectric response with a d33 value as high as ~400 pC/N, which is comparable
to part soft PZTs. As a result, we believe that the general strategy and design
principles described in this study open the possibility of obtaining (K,Na)NbO3
based lead-free ceramics with enhanced properties, expanding their application
range.
PMID- 26436197
TI - Observing the overall rocking motion of a protein in a crystal.
AB - The large majority of three-dimensional structures of biological macromolecules
have been determined by X-ray diffraction of crystalline samples. High-resolution
structure determination crucially depends on the homogeneity of the protein
crystal. Overall 'rocking' motion of molecules in the crystal is expected to
influence diffraction quality, and such motion may therefore affect the process
of solving crystal structures. Yet, so far overall molecular motion has not
directly been observed in protein crystals, and the timescale of such dynamics
remains unclear. Here we use solid-state NMR, X-ray diffraction methods and MUs
long molecular dynamics simulations to directly characterize the rigid-body
motion of a protein in different crystal forms. For ubiquitin crystals
investigated in this study we determine the range of possible correlation times
of rocking motion, 0.1-100 MUs. The amplitude of rocking varies from one crystal
form to another and is correlated with the resolution obtainable in X-ray
diffraction experiments.
PMID- 26436200
TI - Drinking behavior among older adults in a planned retirement community: results
from The Villages survey.
AB - OBJECTIVES: Research indicates increasing trends among older adults toward heavy
and abusive drinking, often associated with depressive symptoms. Possible
exceptions are residents of planned retirement communities, whose drinking may be
associated with social activities. To better understand these relationships, this
study examined the relationship of depressive symptoms and drinking in a large
retirement community. METHODS: The Villages, a retirement community in central
Florida with a focus on healthy, active living, has almost 90,000 residents. In
2012, a population-based needs assessment was conducted in partnership with
University of South Florida Health. In the present study, 11,102 surveys were
completed and returned. A structural equation model was utilized to analyze the
relationship between depressive symptoms and alcohol use as measured by the three
item Alcohol Use Disorders Identification Test (AUDIT-C). RESULTS: Hazardous
drinking was reported in 15.4% of respondents, somewhat higher than the general
population of older adults (around 10%). Variables of depressive symptoms,
physical activity, total health problems, and poor general health loaded
significantly into the factor of depression indicators, which was shown to have a
significant, negative correlation with risk of hazardous drinking (lambda = 0.16,
p < 0.000, R(2) = 0.02). CONCLUSIONS: Results suggest at-risk drinking among
respondents was not associated with depression, in contrast to studies of older
adults living alone where alcohol abuse was often associated with depression.
Implications for successful aging are discussed.
PMID- 26436201
TI - Epidemiological trends among the population with chronic HCV infection in the
Netherlands.
AB - BACKGROUND: As the field of antiviral therapy for chronic HCV infection is
rapidly evolving, this study aimed to assess the epidemiological changes in
patient and disease characteristics among individuals with chronic HCV infection.
METHODS: This study included all consecutive patients with chronic HCV
monoinfection who were referred between 1990 and 2013 to the Erasmus MC
University Medical Center Rotterdam, a large tertiary centre in the Netherlands.
To identify trends over time, the study population was divided into six equal
eras based on date of first visit to the outpatient clinic. RESULTS: A total of
1,779 patients were diagnosed with chronic HCV infection. Mean age increased over
time from 43.6 (sd 13.8) years to 51.7 (sd 11.2) years (P<0.001). The number of
patients who were referred with cirrhosis increased over time, from 31 (25%)
patients in Era 1 to 118 (42%) patients in Era 6 (P<0.001), respectively. More
patients were referred with HCV genotype 1a and 3 in the last era, with 27
(48.2%) and 15 (14.0%) patients in Era 1 and 58 (54.2%) and 60 (21.8%) patients
in Era 6 (P<0.001 both), respectively. The vast majority of patients (69.5%) were
born between 1950 to 1975, with 62.5% of the patients being born between 1945 and
1965. CONCLUSIONS: The HCV-infected population is ageing and is more often
referred with severe liver disease. This study stresses the importance of
urgently implementing national HCV screening programmes in order to be able to
decrease the future burden of chronic HCV infection in the Netherlands.
PMID- 26436202
TI - My epilepsy story--The Anita Kaufmann Foundation.
PMID- 26436203
TI - Dynamic acousto-optic control of a strongly coupled photonic molecule.
AB - Strongly confined photonic modes can couple to quantum emitters and mechanical
excitations. To harness the full potential in quantum photonic circuits,
interactions between different constituents have to be precisely and dynamically
controlled. Here, a prototypical coupled element, a photonic molecule defined in
a photonic crystal membrane, is controlled by a radio frequency surface acoustic
wave. The sound wave is tailored to deliberately switch on and off the bond of
the photonic molecule on sub-nanosecond timescales. In time-resolved experiments,
the acousto-optically controllable coupling is directly observed as clear
anticrossings between the two nanophotonic modes. The coupling strength is
determined directly from the experimental data. Both the time dependence of the
tuning and the inter-cavity coupling strength are found to be in excellent
agreement with numerical calculations. The demonstrated mechanical technique can
be directly applied for dynamic quantum gate operations in state-of-the-art
coupled nanophotonic, quantum cavity electrodynamic and optomechanical systems.
PMID- 26436204
TI - Microfluidic Foaming: A Powerful Tool for Tailoring the Morphological and
Permeability Properties of Sponge-like Biopolymeric Scaffolds.
AB - Ordered porous polymeric materials can be engineered to present highly ordered
pore arrays and uniform and tunable pore size. These features prompted a number
of applications in tissue engineering, generation of meta materials, and
separation and purification of biomolecules and cells. Designing new and
efficient vistas for the generation of ordered porous materials is an active area
of research. Here we investigate the potential of microfluidic foaming within a
flow-focusing (FF) geometry in producing 3D regular sponge-like polymeric
matrices with tailored morphological and permeability properties. The challenge
in using microfluidic systems for the generation of polymeric foams is in the
high viscosity of the continuous phase. We demonstrate that as the viscosity of
the aqueous solution increases, the accessible range of foam bubble fraction
(Phib) and bubble diameter (Db) inside the microfluidic chip tend to narrow
progressively. This effect limits the accessible range of geometric properties of
the resulting materials. We further show that this problem can be rationally
tackled by appropriate choice of the concentration of the polymer. We demonstrate
that via such optimization, the microfluidic assisted synthesis of porous
materials becomes a facile and versatile tool for generation of porous materials
with a wide range of pore size and pore volume. Moreover, we demonstrate that the
size of interconnects among pores-for a given value of the gas fraction-can be
tailored through the variation of surfactant concentration. This, in turn,
affects the permeability of the materials, a factor of key importance in flow
through applications and in tissue engineering.
PMID- 26436205
TI - The application of CD73 in minimal residual disease monitoring using flow
cytometry in B-cell acute lymphoblastic leukemia.
AB - The expression of CD73 by flow cytometry (FC) in bone marrow (BM) specimens of B
cell acute lymphoblastic leukemia (B-ALL) with or without minimal residual
disease (MRD) was studied, and its advantages were evaluated using the MRD assay.
This study also detected the expression profile of CD73 in hematogones and mature
B cells in BM specimens of 18 healthy donors. Results showed that the mean value
of CD73 expression in MRD-positive B cells was 6-fold greater than that in the
MRD negative ones. Also, 41.82% MRD-positive B-ALL cases expressed high CD73 and
the sensitivity of CD73-based MRD detection reached 10(-4). Since the expression
of CD73 increases with the maturation of normal B cells, it is better to mix it
with CD34, CD10 and CD20 in one tube to prevent the disturbance of mature B
cells. CD73 is recommended as an optional MRD marker for B-ALL patients by using
FC.
PMID- 26436206
TI - Trichostatin A and Tamoxifen inhibit breast cancer cell growth by miR-204 and
ERalpha reducing AKT/mTOR pathway.
AB - MicroRNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors.
Increasing evidence suggests that miRNAs are functionally important in cancers.
We demonstrated miR-204 exerts its function by targeting gene involved in tumor
growth and chemotherapy drugs reactivity. Here, we show that Trichostatin A (TSA)
could increase ERalpha expression in MCF-7 and MDA-MB-231 cells by reducing
miR204. Analysis of tumors growth inhibition shows that TSA promotes ERalpha
expression, which could be reversed by miR-204 mimic transfection. When miR-204
is down regulated, the inhibition of TAM on breast cancer cells is enhanced.
Caspase 3 activity is also increased. TSA and TAM combination inhibits Mcl-1
expression by decreasing phosphorylation of AKT induced by ERalpha increase in
vivo and in vitro.
PMID- 26436209
TI - Remote Ischemic Preconditioning in Cardiac Surgery--Ineffective and Risky?
PMID- 26436208
TI - A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery.
AB - BACKGROUND: Remote ischemic preconditioning (RIPC) is reported to reduce
biomarkers of ischemic and reperfusion injury in patients undergoing cardiac
surgery, but uncertainty about clinical outcomes remains. METHODS: We conducted a
prospective, double-blind, multicenter, randomized, controlled trial involving
adults who were scheduled for elective cardiac surgery requiring cardiopulmonary
bypass under total anesthesia with intravenous propofol. The trial compared upper
limb RIPC with a sham intervention. The primary end point was a composite of
death, myocardial infarction, stroke, or acute renal failure up to the time of
hospital discharge. Secondary end points included the occurrence of any
individual component of the primary end point by day 90. RESULTS: A total of 1403
patients underwent randomization. The full analysis set comprised 1385 patients
(692 in the RIPC group and 693 in the sham-RIPC group). There was no significant
between-group difference in the rate of the composite primary end point (99
patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group,
P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4
[0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%],
P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42
[6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol
analysis. No treatment effect was found in any subgroup analysis. No significant
differences between the RIPC group and the sham-RIPC group were seen in the level
of troponin release, the duration of mechanical ventilation, the length of stay
in the intensive care unit or the hospital, new onset of atrial fibrillation, and
the incidence of postoperative delirium. No RIPC-related adverse events were
observed. CONCLUSIONS: Upper-limb RIPC performed while patients were under
propofol-induced anesthesia did not show a relevant benefit among patients
undergoing elective cardiac surgery. (Funded by the German Research Foundation;
RIPHeart ClinicalTrials.gov number, NCT01067703.).
PMID- 26436211
TI - In silico prediction and characterization of protein post-translational
modifications.
AB - This review outlines the computational approaches and procedures for predicting
post translational modification (PTM)-induced changes in protein conformation and
their influence on protein function(s), the latter being assessed as differential
affinity in interaction with either low (ligands for receptors or transporters,
substrates for enzymes) or high molecular mass molecules (proteins or nucleic
acids in supramolecular assemblies). The scope for an in silico approach is
discussed against a summary of the in vitro evidence on the structural and
functional outcome of protein PTM.
PMID- 26436212
TI - Real-World Patterns of Care for the Overactive Bladder Syndrome in the United
States.
AB - OBJECTIVE: To examine the "real-world" overactive bladder (OAB) practice patterns
using national data in the United States. MATERIALS AND METHODS: The Humedica EHR
database was queried. This database consists of de-identified patient records
from a network of organizations treating approximately over 30 million patients
across states in the United States. The entire study period was from July 1,
2008, to September 30, 2013. Patients with a diagnosis of OAB between July 1,
2009, and June 30, 2012 were included and followed. Patient comorbidities,
demographics, diagnostic testing, and medication usage were analyzed. RESULTS: Of
19,309,600 subjects enrolled during the study period, 46,648 adults had a
diagnosis of OAB, with follow-up of at least 6 months, and met the inclusion
criteria. There were 35,315 women and 11,333 men. Compared with women, men with
OAB were more likely to undergo post-void residual measurement (32% vs 22%) and
diagnostic cystoscopy (10% vs 7%). Women were more likely than men to undergo
urodynamics (7% vs 3%). Overall, 34% of women and 19% of men diagnosed with OAB
were prescribed medication. CONCLUSION: Few patients with OAB underwent invasive
diagnostic testing. Anticholinergic medication was prescribed to a minority of
patients diagnosed with OAB, indicating possible underuse of a potentially
effective therapy. Men were less likely than women to receive medical therapy,
despite the fact that OAB is common in both sexes.
PMID- 26436213
TI - The Clinical and Urodynamic Results of Percutaneous Posterior Tibial Nerve
Stimulation on Neurogenic Detrusor Overactivity in Patients With Parkinson's
Disease.
AB - OBJECTIVE: To investigate the effect of percutaneous posterior tibial nerve
stimulation (PTNS) treatment after 12 weeks on urodynamic and clinical findings
in patients with Parkinson's disease (PD) with neurogenic detrusor overactivity.
METHODS: A total of 47 patients with PD with neurogenic detrusor overactivity
were enrolled in the study. Urodynamic studies before and after 12-week PTNS
treatment were performed. International Consultation on Incontinence
Questionnaire Short Form (ICIQ-SF), Overactive Bladder Questionnaire (OAB-V8),
and Overactive Bladder Questionnaire Short Form (OAB-q SF) have been assessed
before and after PTNS treatment. RESULTS: The mean first involuntary detrusor
contraction volume (1st IDCV) on standard cystometry was 133.2 +/- 48.1 (24-265)
mL, whereas it was 237.3 +/- 43.1 (145-390) mL after PTNS. The mean maximum
cystometric capacity (MCC) on standard cystometry was 202.2 +/- 36.5 (115-320)
mL, whereas it was 292.1 +/- 50.6 (195-395) mL after stimulation. The
improvements in the first involuntary detrusor contraction volume and maximum
cystometric capacity were statistically significant after stimulation. The mean
Pdetmax at first involuntary detrusor contraction, maximal detrusor pressure at
maximum cystometric capacity, PdetQmax, Qmax, and post-void residual volume were
statistically significant after 12-week stimulation. Mean parametric improvements
at 12-week PTNS treatment from baseline included daytime frequency decreased by
5.6 voids daily, urge incontinence decreased by 3.1 episodes daily, urgency
episodes decreased by 6.3 episodes daily, nocturia decreased by 2.7 voids, and
voided volume improved by a mean of 92.6 mL. The change from baseline on the ICIQ
SF, OABv8, and OAB-q at 12-week PTNS treatment demonstrated statistically
significant improvements. CONCLUSION: These results have demonstrated that PTNS
improves the lower urinary tract symptoms and urodynamic parameters in patients
with PD.
PMID- 26436214
TI - Metal release from coffee machines and electric kettles.
AB - The release of elemental ions from 8 coffee machines and 11 electric kettles into
food simulants was investigated. Three different types of coffee machines were
tested: portafilter espresso machines, pod machines and capsule machines. All
machines were tested subsequently on 3 days before and on 3 days after
decalcification. Decalcification of the machines was performed with agents
according to procedures as specified in the respective manufacturer's manuals.
The electric kettles showed only a low release of the elements analysed. For the
coffee machines decreasing concentrations of elements were found from the first
to the last sample taken in the course of 1 day. Metal release on consecutive
days showed a decreasing trend as well. After decalcification a large increase in
the amounts of elements released was encountered. In addition, the different
machine types investigated clearly differed in their extent of element release.
By far the highest leaching, both quantitatively and qualitatively, was found for
the portafilter machines. With these products releases of Pb, Ni, Mn, Cr and Zn
were in the range and beyond the release limits as proposed by the Council of
Europe. Therefore, a careful rinsing routine, especially after decalcification,
is recommended for these machines. The comparably lower extent of release of one
particular portafilter machine demonstrates that metal release at levels above
the threshold that triggers health concerns are technically avoidable.
PMID- 26436215
TI - A Rare Mechanism of Hyponatremia in HIV Disease.
AB - BACKGROUND: Hyponatremia is the most common disorder of body fluid and
electrolyte balance in clinical practice. It is associated with increased
morbidity, mortality, and length of hospital stay. Little is known about the
relationship between hyponatremia and HIV disease. It is thought that
hyponatremia in HIV is associated with a syndrome of inappropriate ADH secretion
(SIADH), volume depletion, and adrenal insufficiency. Another common association
is with Pneumocystis jirovecii (PCP). In early 1990s, there were several reports
linking hyponatremia and HIV disease. It was found that these patients with
acquired immune deficiency syndrome (AIDS) had abnormal adrenal cortical
function. Additionally, these patients showed an abnormally elevated baseline
cortisol level and a blunted response to cosyntropin. CASE REPORT: Here, we
present the case of an HIV patient presenting with hyponatremia and a physical
examination suggestive of hypovolemia. Laboratory tests revealed urinary loss of
sodium in the setting of normal serum cortisol level. The patient responded well
to the administration of a mineralocorticoid hormone. CONCLUSIONS: Glucocorticoid
resistance is an unusual cause of hyponatremia, and needs to be identified and
treated accordingly.
PMID- 26436217
TI - Investigation of Child Restraint System (CRS) Compatibility in the Vehicle Seat
Environment.
AB - OBJECTIVE: Child restraint system (CRS) misuse is common and can have serious
consequences to child safety. Physical incompatibilities between CRS and vehicles
can complicate the installation process and may worsen CRS misuse rates. This
study aims to identify the most common sources of incompatibility between
representative groups of CRS and vehicles. METHODS: Detailed dimensional data
were collected from 59 currently marketed CRS and 61 late model vehicles. Key
dimensions were compared across all 3,599 theoretical CRS/vehicle combinations
and the most common predicted incompatibilities were determined. A subset of 34
physical installations was analyzed to validate the results. RESULTS: Only 58.2%
of rear-facing (RF) CRS/vehicle combinations were predicted to have proper
agreement between the vehicle's seat pan angle and the CRS manufacturers'
required base angle. The width of the base of the CRS was predicted to fit snugly
between the vehicle's seat pan bolsters in 63.3% of RF CRS/vehicle combinations
and 62.2% of forward-facing (FF) CRS/vehicle combinations. FF CRS were predicted
to be free of interaction with the vehicle's head restraint in 66.4% of
combinations. Roughly 90.0% of RF CRS/vehicle combinations were predicted to have
enough horizontal clearance space to set the front seat in the middle its
fore/aft slider track. Compatibility rates were above 98% regarding the length of
the CRS base compared to the length of the vehicle seat pan and the ability of
the top tether to reach the tether anchor. Validation studies revealed that the
predictions of RF CRS base angle range vs. seat pan angle compatibility were
accurate within 6%, and head restraint interference and front row clearance
incompatibilities may be more common than the dimensional analysis approach has
predicted. CONCLUSIONS: The results of this study indicate that RF CRS base
angles and front row clearance space, as well as FF CRS head restraint
interference, are frequent compatibility concerns. These results enable
manufacturers, researchers, and consumers to focus their attention on the most
relevant CRS/vehicle incompatibility issues in today's market.
PMID- 26436218
TI - Injury Outcome in Crashes with Guardrail End Terminals.
AB - OBJECTIVE: The goal of this study is to evaluate the crash performance of
guardrail end terminals in real-world crashes. Guardrail end terminals are
installed at the ends of guardrail systems to prevent the rail from spearing
through the car in an end-on collision. Recently, there has been a great deal of
controversy as to the safety of certain widely used end terminal designs, partly
because there is surprisingly little real-world crash data for end terminals.
Most existing studies of end terminal crashes used data from prior to the mid
1990s. Since then, there have been large improvements to vehicle crashworthiness
and seat belt usage rates, as well as new roadside safety hardware compliant with
National Cooperative Highway Research Program (NCHRP) Report 350, "Recommended
Procedures for the Safety Performance Evaluation of Highway Features."
Additionally, most existing studies of injury in end terminal crashes do not
account for factors such as the occurrence of rollover. This analysis uses more
recent crash data that represent post-1990s vehicle fleet changes and account for
a number of factors that may affect driver injury outcome and rollover
occurrence. METHODS: Passenger vehicle crashes coded as involving guardrail end
terminals were identified in the set of police-reported crashes in Michigan in
2011 and 2012. End terminal performance was expected to be a function of end
terminal system design. State crash databases generally do not identify specific
end terminal systems. In this study, the coded crash location was used to obtain
photographs of the crash site prior to the crash from Google Street View. These
site photographs were manually inspected to identify the particular end terminal
system involved in the crash. Multiple logistic regression was used to test for
significant differences in the odds of driver injury and rollover between
different terminal types while accounting for other factors. RESULTS: A total of
1,001 end terminal crashes from the 2011-2012 Michigan State crash data were
manually inspected to identify the terminal that had been struck. Four hundred
fifty-one crashes were found to be suitable for analysis. Serious to fatal driver
injury occurred in 3.8% of end terminal crashes, moderate to fatal driver injury
occurred in 11.8%, and 72.3% involved property damage only. No significant
difference in moderate to fatal driver injury odds was observed between NCHRP 350
compliant end terminals and noncompliant terminals. Car drivers showed odds of
moderate to fatal injury 3.6 times greater than LTV drivers in end terminal
crashes. Rollover occurrence was not significantly associated with end terminal
type. CONCLUSIONS: Car drivers have greater potential for injury in end terminal
crashes than light truck/van/sport utility vehicle drivers. End terminal designs
compliant with NCHRP 350 did not appear to carry different odds of moderate
driver injury than noncompliant end terminals. The findings account for driver
seat belt use, rollover occurrence, terminal orientation (leading/trailing),
control loss, and the number of impact events. Rollover and nonuse of seat belts
carried much larger increases in injury potential than end terminal type.
Rollover did not appear to be associated with NCHRP 350 compliance.
PMID- 26436219
TI - Comparison of Expected Crash and Injury Reduction from Production Forward
Collision and Lane Departure Warning Systems.
AB - OBJECTIVES: The U.S. New Car Assessment Program (NCAP) now tests for forward
collision warning (FCW) and lane departure warning (LDW). The design of these
warnings differs greatly between vehicles and can result in different real-world
field performance in preventing or mitigating the effects of collisions. The
objective of this study was to compare the expected number of crashes and injured
drivers that could be prevented if all vehicles in the fleet were equipped with
the FCW and LDW systems tested under the U.S. NCAP. METHODS: To predict the
potential crashes and serious injury that could be prevented, our approach was to
computationally model the U.S. crash population. The models simulated all rear
end and single-vehicle road departure collisions that occurred in a nationally
representative crash database (NASS-CDS). A sample of 478 single-vehicle crashes
from NASS-CDS 2012 was the basis for 24,822 simulations for LDW. A sample of
1,042 rear-end collisions from NASS-CDS years 1997-2013 was the basis for 7,616
simulations for FCW. For each crash, 2 simulations were performed: (1) without
the system present and (2) with the system present. Models of each production
safety system were based on 54 model year 2010-2014 vehicles that were evaluated
under the NCAP confirmation procedure for LDW and/or FCW. NCAP performed 40 LDW
and 45 FCW tests of these vehicles. RESULTS: The design of the FCW systems had a
dramatic impact on their potential to prevent crashes and injuries. Between 0 and
67% of crashes and 2 and 69% of moderately to fatally injured drivers in rear-end
impacts could have been prevented if all vehicles were equipped with the FCW
systems. Earlier warning times resulted in increased benefits. The largest effect
on benefits, however, was the lower operating speed threshold of the systems.
Systems that only operated at speeds above 20 mph were less than half as
effective as those that operated above 5 mph with similar warning times. The
production LDW systems could have prevented between 11 and 23% of drift-out-of
lane crashes and 13 and 22% of seriously to fatally injured drivers. A majority
of the tested LDW systems delivered warnings near the point when the vehicle
first touched the lane line, leading to similar benefits. Minimum operating speed
also greatly affected LDW effectiveness. CONCLUSIONS: The results of this study
show that the expected field performance of FCW and LDW systems are highly
dependent on the design and system limitations. Systems that delivered warnings
earlier and operated at lower speeds may prevent far more crashes and injuries
than systems that warn late and operate only at high speeds. These results
suggest that future FCW and LDW evaluation should prioritize early warnings and
full-speed range operation. A limitation of this study is that additional crash
avoidance features that may also mitigate collisions-for example, brake assist,
automated braking, or lane-keeping assistance-were not evaluated during the NCAP
tests or in our benefits models. The potential additional mitigating effects of
these systems were not quantified in this study.
PMID- 26436220
TI - Real-World Rib Fracture Patterns in Frontal Crashes in Different Restraint
Conditions.
AB - OBJECTIVE: The purpose of this study was to use the detailed medical injury
information in the Crash Injury Research and Engineering Network (CIREN) to
evaluate patterns of rib fractures in real-world crash occupants in both belted
and unbelted restraint conditions. Fracture patterns binned into rib regional
levels were examined to determine normative trends associated with belt use and
other possible contributing factors. METHODS: Front row adult occupants with
Abbreviated Injury Scale (AIS) 3+ rib fractures, in frontal crashes with a
deployed frontal airbag, were selected from the CIREN database. The
circumferential location of each rib fracture (with respect to the sternum) was
documented using a previously published method (Ritchie et al. 2006) and digital
computed tomography scans. Fracture patterns for different crash and occupant
parameters (restraint use, involved physical component, occupant kinematics,
crash principal direction of force, and occupant age) were compared qualitatively
and quantitatively. RESULTS: There were 158 belted and 44 unbelted occupants
included in this study. For belted occupants, fractures were mainly located near
the path of the shoulder belt, with the majority of fractures occurring on the
inboard (with respect to the vehicle) side of the thorax. For unbelted occupants,
fractures were approximately symmetric and distributed across both sides of the
thorax. There were negligible differences in fracture patterns between occupants
with frontal (0 degrees ) and near side (330 degrees to 350 degrees for
drivers; 10 degrees to 30 degrees for passengers) crash principal directions of
force but substantial differences between groups when occupant kinematics (and
contacts within the vehicle) were considered. Age also affected fracture pattern,
with fractures tending to occur more anteriorly in older occupants and more
laterally in younger occupants (both belted and unbelted). CONCLUSIONS: Results
of this study confirmed with real-world data that rib fracture patterns in
unbelted occupants were more distributed and symmetric across the thorax compared
to belted occupants in crashes with a deployed frontal airbag. Other factors,
such as occupant kinematics and occupant age, also produced differing patterns of
fractures. Normative data on rib fracture patterns in real-world occupants can
contribute to understanding injury mechanisms and the role of different causation
factors, which can ultimately help prevent fractures and improve vehicle safety.
PMID- 26436207
TI - Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery.
AB - BACKGROUND: Whether remote ischemic preconditioning (transient ischemia and
reperfusion of the arm) can improve clinical outcomes in patients undergoing
coronary-artery bypass graft (CABG) surgery is not known. We investigated this
question in a randomized trial. METHODS: We conducted a multicenter, sham
controlled trial involving adults at increased surgical risk who were undergoing
on-pump CABG (with or without valve surgery) with blood cardioplegia. After
anesthesia induction and before surgical incision, patients were randomly
assigned to remote ischemic preconditioning (four 5-minute inflations and
deflations of a standard blood-pressure cuff on the upper arm) or sham
conditioning (control group). Anesthetic management and perioperative care were
not standardized. The combined primary end point was death from cardiovascular
causes, nonfatal myocardial infarction, coronary revascularization, or stroke,
assessed 12 months after randomization. RESULTS: We enrolled a total of 1612
patients (811 in the control group and 801 in the ischemic-preconditioning group)
at 30 cardiac surgery centers in the United Kingdom. There was no significant
difference in the cumulative incidence of the primary end point at 12 months
between the patients in the remote ischemic preconditioning group and those in
the control group (212 patients [26.5%] and 225 patients [27.7%], respectively;
hazard ratio with ischemic preconditioning, 0.95; 95% confidence interval, 0.79
to 1.15; P=0.58). Furthermore, there were no significant between-group
differences in either adverse events or the secondary end points of perioperative
myocardial injury (assessed on the basis of the area under the curve for the high
sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated
from the maximum dose of the individual inotropic agents administered in the
first 3 days after surgery), acute kidney injury, duration of stay in the
intensive care unit and hospital, distance on the 6-minute walk test, and quality
of life. CONCLUSIONS: Remote ischemic preconditioning did not improve clinical
outcomes in patients undergoing elective on-pump CABG with or without valve
surgery. (Funded by the Efficacy and Mechanism Evaluation Program [a Medical
Research Council and National Institute of Health Research partnership] and the
British Heart Foundation; ERICCA ClinicalTrials.gov number, NCT01247545.).
PMID- 26436221
TI - Driver Injury Risk Variability in Finite Element Reconstructions of Crash Injury
Research and Engineering Network (CIREN) Frontal Motor Vehicle Crashes.
AB - OBJECTIVE: A 3-phase real-world motor vehicle crash (MVC) reconstruction method
was developed to analyze injury variability as a function of precrash occupant
position for 2 full-frontal Crash Injury Research and Engineering Network (CIREN)
cases. METHOD: Phase I: A finite element (FE) simplified vehicle model (SVM) was
developed and tuned to mimic the frontal crash characteristics of the CIREN case
vehicle (Camry or Cobalt) using frontal New Car Assessment Program (NCAP) crash
test data. Phase II: The Toyota HUman Model for Safety (THUMS) v4.01 was
positioned in 120 precrash configurations per case within the SVM. Five occupant
positioning variables were varied using a Latin hypercube design of experiments:
seat track position, seat back angle, D-ring height, steering column angle, and
steering column telescoping position. An additional baseline simulation was
performed that aimed to match the precrash occupant position documented in CIREN
for each case. Phase III: FE simulations were then performed using kinematic
boundary conditions from each vehicle's event data recorder (EDR). HIC15,
combined thoracic index (CTI), femur forces, and strain-based injury metrics in
the lung and lumbar vertebrae were evaluated to predict injury. RESULTS: Tuning
the SVM to specific vehicle models resulted in close matches between simulated
and test injury metric data, allowing the tuned SVM to be used in each case
reconstruction with EDR-derived boundary conditions. Simulations with the most
rearward seats and reclined seat backs had the greatest HIC15, head injury risk,
CTI, and chest injury risk. Calculated injury risks for the head, chest, and
femur closely correlated to the CIREN occupant injury patterns. CTI in the Camry
case yielded a 54% probability of Abbreviated Injury Scale (AIS) 2+ chest injury
in the baseline case simulation and ranged from 34 to 88% (mean = 61%) risk in
the least and most dangerous occupant positions. The greater than 50% probability
was consistent with the case occupant's AIS 2 hemomediastinum. Stress-based
metrics were used to predict injury to the lower leg of the Camry case occupant.
The regional-level injury metrics evaluated for the Cobalt case occupant
indicated a low risk of injury; however, strain-based injury metrics better
predicted pulmonary contusion. Approximately 49% of the Cobalt occupant's left
lung was contused, though the baseline simulation predicted 40.5% of the lung to
be injured. CONCLUSIONS: A method to compute injury metrics and risks as
functions of precrash occupant position was developed and applied to 2 CIREN MVC
FE reconstructions. The reconstruction process allows for quantification of the
sensitivity and uncertainty of the injury risk predictions based on occupant
position to further understand important factors that lead to more severe MVC
injuries.
PMID- 26436222
TI - Evaluation of Vehicle-Based Crash Severity Metrics.
AB - OBJECTIVE: Vehicle change in velocity (delta-v) is a widely used crash severity
metric used to estimate occupant injury risk. Despite its widespread use, delta-v
has several limitations. Of most concern, delta-v is a vehicle-based metric which
does not consider the crash pulse or the performance of occupant restraints, e.g.
seatbelts and airbags. Such criticisms have prompted the search for alternative
impact severity metrics based upon vehicle kinematics. The purpose of this study
was to assess the ability of the occupant impact velocity (OIV), acceleration
severity index (ASI), vehicle pulse index (VPI), and maximum delta-v (delta-v) to
predict serious injury in real world crashes. METHODS: The study was based on the
analysis of event data recorders (EDRs) downloaded from the National Automotive
Sampling System / Crashworthiness Data System (NASS-CDS) 2000-2013 cases. All
vehicles in the sample were GM passenger cars and light trucks involved in a
frontal collision. Rollover crashes were excluded. Vehicles were restricted to
single-event crashes that caused an airbag deployment. All EDR data were checked
for a successful, completed recording of the event and that the crash pulse was
complete. The maximum abbreviated injury scale (MAIS) was used to describe
occupant injury outcome. Drivers were categorized into either non-seriously
injured group (MAIS2-) or seriously injured group (MAIS3+), based on the severity
of any injuries to the thorax, abdomen, and spine. ASI and OIV were calculated
according to the Manual for Assessing Safety Hardware. VPI was calculated
according to ISO/TR 12353-3, with vehicle-specific parameters determined from
U.S. New Car Assessment Program crash tests. Using binary logistic regression,
the cumulative probability of injury risk was determined for each metric and
assessed for statistical significance, goodness-of-fit, and prediction accuracy.
RESULTS: The dataset included 102,744 vehicles. A Wald chi-square test showed
each vehicle-based crash severity metric estimate to be a significant predictor
in the model (p < 0.05). For the belted drivers, both OIV and VPI were
significantly better predictors of serious injury than delta-v (p < 0.05). For
the unbelted drivers, there was no statistically significant difference between
delta-v, OIV, VPI, and ASI. CONCLUSIONS: The broad findings of this study suggest
it is feasible to improve injury prediction if we consider adding restraint
performance to classic measures, e.g. delta-v. Applications, such as advanced
automatic crash notification, should consider the use of different metrics for
belted versus unbelted occupants.
PMID- 26436223
TI - Implications of Functional Capacity Loss and Fatality for Vehicle Safety
Prioritization.
AB - OBJECTIVE: We investigate the use of the Functional Capacity Index (FCI) as a
tool for establishing vehicle safety priorities by comparing the life year burden
of injuries to the burden of fatality in frontal and side automotive crashes. We
demonstrate FCI's utility by investigating in detail the resulting disabling
injuries and their life year costs. METHODS: We selected occupants in the 2000
2013 NASS-CDS database involved in frontal and side crashes, merged their
injuries with FCI, and then used the merged data to estimate each occupant's
overall functional loss. Lifetime functional loss was assessed by combining this
measure of impairment with the occupants' expected future life spans, estimated
from the Social Security Administration's Actuarial Life Table. RESULTS: Frontal
crashes produce a large number of disabling injuries, particularly to the lower
extremities. In our population, these crashes are estimated to account for
approximately 400,000 life years lost to disability in comparison with 500,000
life years lost to fatality. Victims of side crashes experienced a higher rate of
fatality but a significantly lower rate of disabling injury (0.3 vs. 1.0%),
resulting in approximately 370,000 life years lost to fatality versus 50,000 life
years lost to disability. CONCLUSIONS: The burden of disabling injuries to car
crash survivors should be considered when setting vehicle safety design
priorities. In frontal crashes this burden in life years is similar to the burden
attributable to fatality.
PMID- 26436224
TI - Association Between NCAP Ratings and Real-World Rear Seat Occupant Risk of
Injury.
AB - OBJECTIVE: Several studies have evaluated the correlation between U.S. or Euro
New Car Assessment Program (NCAP) ratings and injury risk to front seat
occupants, in particular driver injuries. Conversely, little is known about
whether NCAP 5-star ratings predict real-world risk of injury to restrained rear
seat occupants. The NHTSA has identified rear seat occupant protection as a
specific area under consideration for improvements to its NCAP. In order to
inform NHTSA's efforts, we examined how NCAP's current 5-star rating system
predicts risk of moderate or greater injury among restrained rear seat occupants
in real-world crashes. METHODS: We identified crash-involved vehicles, model year
2004-2013, in NASS-CDS (2003-2012) with known make and model and nonmissing
occupant information. We manually matched these vehicles to their NCAP star
ratings using data on make, model, model year, body type, and other identifying
information. The resultant linked NASS-CDS and NCAP database was analyzed to
examine associations between vehicle ratings and rear seat occupant injury risk;
risk to front seat occupants was also estimated for comparison. Data were limited
to restrained occupants and occupant injuries were defined as any injury with a
maximum Abbreviated Injury Scale (AIS) score of 2 or greater. RESULTS: We linked
95% of vehicles in NASS-CDS to a specific vehicle in NCAP. The 18,218 vehicles
represented an estimated 6 million vehicles with over 9 million occupants. Rear
seat passengers accounted for 12.4% of restrained occupants. The risk of injury
in all crashes for restrained rear seat occupants was lower in vehicles with a 5
star driver rating in frontal impact tests (1.4%) than with 4 or fewer stars
(2.6%, P =.015); results were similar for the frontal impact passenger rating
(1.3% vs. 2.4%, P =.024). Conversely, side impact driver and passenger crash
tests were not associated with rear seat occupant injury risk (driver test: 1.7%
for 5-star vs. 1.8% for 1-4 stars; passenger test: 1.6% for 5 stars vs 1.8% for 1
4 stars). CONCLUSIONS: Current frontal impact test procedures provide some degree
of discrimination in real-world rear seat injury risk among vehicles with 5
compared to fewer than 5 stars. However, there is no evidence that vehicles with
a 5-star side impact passenger rating, which is the only crash test procedure to
include an anthropomorphic test dummy (ATD) in the rear, demonstrate lower risks
of injury in the rear than vehicles with fewer than 5 stars. These results
support prioritizing modifications to the NCAP program that specifically evaluate
rear seat injury risk to restrained occupants of all ages.
PMID- 26436226
TI - Effects of LATCH versus Available Seatbelt Installation of Rear Facing Child
Restraint Systems on Head Injury Criteria for 6 Month Old Infants in Rear End
Collisions.
AB - OBJECTIVE: The Lower Anchor and Tethers for CHildren (LATCH) system was
introduced in vehicles made after September 1, 2002 and intended to make
installation of rear and forward-facing child safety seats easier. Due to the
lack of rear impact testing of RFCRS required per the Federal Motor Vehicle
Safety Standards (FMVSS), the purpose of this study was to explore the effects,
if any, of installation method of RFCRS on the performance of commonly purchased
makes and models of RFCRS. Specifically, we hypothesize that in a 48 km/h (29.8
MPH) rear-end collision, installation of RFCRS using the LATCH system will result
in higher Head Injury Criteria (HIC) values when compared to using the available
lap/shoulder seatbelt (Emergency Locking Retractor - ELR or Automatic Locking
Retractor - ALR). METHODS: The test matrix included 36 rear impact sled tests
conducted using 3 installation methods on 3 models of RFCRS: the Graco
SnugRide(r) with and without the base, the Britax Chaperone with base-mounted
anti-rebound bar, and the Evenflo Tribute(r), a model of convertible
rearward/forward facing restraint system used in the rearward facing mode. The
seats were installed using the LATCH system, ELR lap/shoulder belts, or ALR
lap/shoulder belts in seating positions 4 and 6 on a vehicle buck mounted to the
sled test base. The infant seat and 6 month old CRABI anthropometric test device
(ATD) installation methods were in accordance with standards set forth in the
National Highway Traffic Safety Administration's (NHTSA) FMVSS No. 213, Child
Restraint Systems. All tests were conducted on pneumatic controlled acceleration
sled (HYGE, Inc., PA, USA) at 48 km/h. RESULTS: Installation of infant seat type
RFCRS using the LATCH system resulted in higher HIC15 values when compared to
using the available lap/shoulder seatbelt (ELR or ALR). The mean HIC15 values
were most severe when infant seat type RFCRS were installed using LATCH (Graco
SnugRide(r) HIC15 = 394 and Britax Chaperone HIC15 = 133) compared to using
either ELR lap/shoulder belts (Graco SnugRide(r) HIC15 = 218 and Britax Chaperone
HIC15 = 65) or ALR lap/shoulder belts (Graco SnugRide(r) HIC15 = 194 and Britax
Chaperone HIC15 = 78). The installation method did not result in a statistically
significant difference in HIC for the convertible type RFCRS (Evenflo
Tribute(r)). In many of the tests, the ATD's head struck the seatback in which
the RFCRS was installed. These head strikes resulted in the higher HIC15 scores
recorded throughout the testing. CONCLUSIONS: The results of this study suggest
that LATCH does not offer equal protection to lap/shoulder belts from head
injuries in rear impacts when used with infant seat type RFCRS.
PMID- 26436225
TI - Lumbar Bone Mineral Density Phantomless Computed Tomography Measurements and
Correlation with Age and Fracture Incidence.
AB - OBJECTIVE: Low bone quality is a contributing factor to motor vehicle crash (MVC)
injury. Quantification of occupant bone mineral density (BMD) is important from
an injury causation standpoint. The first aim of this study was to validate a
technique for measuring lumbar volumetric BMD (vBMD) from phantomless computed
tomography (CT) scans. The second aim was to apply the validated phantomless
technique to quantify lumbar vBMD in Crash Injury Research and Engineering
Network (CIREN) occupants for correlation with age, fracture incidence, and
osteopenia/osteoporosis diagnoses. METHODS: Quantitative CT (qCT) and dual-energy
X-ray absorptiometry (DXA) were collected prospectively for 50 subjects and used
to validate a technique to measure vBMD from 281 phantomless CT scans of CIREN
occupants. Hounsfield unit (HU) measurements were collected from the L1-L5
vertebrae, right psoas major muscle, and anterior subcutaneous fat for all
subjects and from 3 phantom ports with known mg/cc calcium hydroxyapatite values
for the validation group. qCT calibration was accomplished using regressions
between the phantom HU and mg/cc values to convert L1-L5 HU values to mg/cc. A
phantomless calibration technique was developed where the fat and muscle HU
values were linearly regressed against fat (-69 mg/cc) and muscle (77 mg/cc) to
establish a conversion for L1-L5 HU measurements to mg/cc. vBMD calculated from
qCT versus the phantomless method was compared for the 50 subjects to assess
agreement and a mg/cc osteopenia threshold was established using DXA T-scores.
CIREN HU measurements were converted to mg/cc using the phantomless technique and
the mg/cc osteopenia threshold was used to compare vBMD to age, fracture
incidence, and osteopenia comorbidity classifications in CIREN. RESULTS: Linear
regression of lumbar vBMD derived from the qCT versus phantomless calibrations
showed excellent agreement (R(2) = 0.87, P <.0001). A 145 mg/cc threshold for
osteopenia was established (sensitivity = 1, specificity = 0.57) and 44 CIREN
occupants had vBMD below this threshold. Of these 44 occupants, 64% were not
classified as osteopenic in CIREN, but vBMD suggested undiagnosed osteopenia. Age
was negatively correlated with vBMD in both sexes (P <.0001) and CIREN occupants
with less than 145 mg/cc vBMD sustained an average 1.7 additional rib/sternum
fractures (P =.036). CONCLUSIONS: Because lumbar vBMD was estimated from
phantomless CT scans with accuracy similar to qCT, the phantomless technique can
be broadly applied to both prospectively and retrospectively assess patient bone
quality for research and clinical studies related to MVCs, falls, and aging.
PMID- 26436227
TI - Older Adults at Increased Risk as Pedestrians in Victoria, Australia: An
Examination of Crash Characteristics and Injury Outcomes.
AB - OBJECTIVES: Engaging in active transport modes (especially walking) is a healthy
and environmentally friendly alternative to driving and may be particularly
beneficial for older adults. However, older adults are a vulnerable group: they
are at higher risk of injury compared with younger adults, mainly due to frailty
and may be at increased risk of collision due to the effects of age on sensory,
cognitive, and motor abilities. Moreover, our population is aging, and there is a
trend for the current cohort of older adults to maintain mobility later in life
compared with previous cohorts. Though these trends have serious implications for
transport policy and safety, little is known about the contributing factors and
injury outcomes of pedestrian collision. Further, previous research generally
considers the older population as a homogeneous group and rarely considers the
increased risks associated with continued ageing. METHOD: Collision
characteristics and injury outcomes for 2 subgroups of older pedestrians (65-74
years and 75+ years) were examined by extracting data from the state police
reported crash dataset and hospital admission/emergency department presentation
data over the 10-year period between 2003 and 2012. Variables identified for
analysis included pedestrian characteristics (age, gender, activity, etc.), crash
location and type, injury characteristics and severity, and duration of hospital
stay. A spatial analysis of crash locations was also undertaken to identify
collision clusters and the contribution of environmental features on collision
and injury risk. RESULTS: Adults over 65 years were involved in 21% of all
pedestrian collisions. A high fatality rate was found among older adults,
particularly for those aged 75 years and older: this group had 3.2 deaths per
100,000 population, compared to a rate of 1.3 for 65- to 74-year-olds and 0.7 for
adults below 65 years of age. Older pedestrian injuries were most likely to occur
while crossing the carriageway; they were also more likely to be injured in
parking lots, at driveway intersections, and on sidewalks compared to younger
cohorts. Spatial analyses revealed older pedestrian crash clusters on arterial
roads in urban shopping precincts. Significantly higher rates of hospital
admissions were found for pedestrians over the age of 75 years and for abdominal,
head, and neck injuries; conversely, older adults were underrepresented in
emergency department presentations (mainly lower and upper extremity injuries),
suggesting an increased severity associated with older pedestrian injuries.
Average length of hospital stay also increased with increasing age. CONCLUSION:
This analysis revealed age differences in collision risk and injury outcomes
among older adults and that aggregate analysis of older pedestrians can distort
the significance of risk factors associated with older pedestrian injuries. These
findings have implications that extend to the development of engineering,
behavioral, and enforcement countermeasures to address the problems faced by the
oldest pedestrians and reduce collision risk and improve injury outcomes.
PMID- 26436228
TI - Biofidelity Corridors for Sternum Kinematics in Low-Speed Side Impacts.
AB - OBJECTIVE: Field data show that side impact car crashes have become responsible
for a greater proportion of the fatal crashes compared to frontal crashes, which
suggests that the protection gained in frontal impact has not been matched in
side impact. One of the reasons is the lack of understanding of the torso injury
mechanisms in side impact. In particular, the deformation of the rib cage and how
it affects the mechanical loading of the individual ribs have yet to be
established. Therefore, the objective of this study was to characterize the
ribcage deformation in side impacts by describing the kinematics of the sternum
relative to the spine. METHODS: The 3D kinematics of the 1st and of the 5th or
6th thoracic vertebrae and of the sternum were obtained for three Post Mortem
Human Subjects (PMHS) impacted laterally by a rigid wall traveling at 15 km/h.
The experimental data were processed to express the kinematics of the sternum
relative to the spine throughout the impact event. Methods were developed to
interpolate the kinematics of the vertebrae for which experimental data were not
available. RESULTS: The kinematics of the sternocostal junction for ribs 1 to 6
as well as the orientation of the sternum were expressed in the vertebra
coordinate systems defined for each upper thoracic vertebra (T1 to T6). Corridors
were designed for the motion of the sternum relative to each vertebra. In the
experiments, the sternum moved upward for all rib levels (1 to 6), and away from
the spine with an amplitude that increased with the decreasing rib level (from
rib 1 to rib 6). None of the differences observed in the kinematics could be
correlated to the occurrence of rib fractures. CONCLUSIONS: This study provides
both qualitative and quantitative information for the ribcage skeletal kinematics
in side impact. This data set provides the information required to better
evaluate computational models of the thorax for side impact simulations. The
corridors developed in this study provide new biofidelity targets for the impact
response of the ribcage. This study contributes to augmenting the state of
knowledge of the human chest deformation in side impact to better characterize
the rib fracture mechanisms.
PMID- 26436229
TI - Driver Behavior During Overtaking Maneuvers from the 100-Car Naturalistic Driving
Study.
AB - OBJECTIVE: Lane changes with the intention to overtake the vehicle in front are
especially challenging scenarios for forward collision warning (FCW) designs.
These overtaking maneuvers can occur at high relative vehicle speeds and often
involve no brake and/or turn signal application. Therefore, overtaking presents
the potential of erroneously triggering the FCW. A better understanding of driver
behavior during lane change events can improve designs of this human-machine
interface and increase driver acceptance of FCW. The objective of this study was
to aid FCW design by characterizing driver behavior during lane change events
using naturalistic driving study data. METHODS: The analysis was based on data
from the 100-Car Naturalistic Driving Study, collected by the Virginia Tech
Transportation Institute. The 100-Car study contains approximately 1.2 million
vehicle miles of driving and 43,000 h of data collected from 108 primary drivers.
In order to identify overtaking maneuvers from a large sample of driving data, an
algorithm to automatically identify overtaking events was developed. The lead
vehicle and minimum time to collision (TTC) at the start of lane change events
was identified using radar processing techniques developed in a previous study.
The lane change identification algorithm was validated against video analysis,
which manually identified 1,425 lane change events from approximately 126 full
trips. RESULTS: Forty-five drivers with valid time series data were selected from
the 100-Car study. From the sample of drivers, our algorithm identified 326,238
lane change events. A total of 90,639 lane change events were found to involve a
closing lead vehicle. Lane change events were evenly distributed between left
side and right side lane changes. The characterization of lane change frequency
and minimum TTC was divided into 10 mph speed bins for vehicle travel speeds
between 10 and 90 mph. For all lane change events with a closing lead vehicle,
the results showed that drivers change lanes most frequently in the 40-50 mph
speed range. Minimum TTC was found to increase with travel speed. The variability
in minimum TTC between drivers also increased with travel speed. CONCLUSIONS:
This study developed and validated an algorithm to detect lane change events in
the 100-Car Naturalistic Driving Study and characterized lane change events in
the database. The characterization of driver behavior in lane change events
showed that driver lane change frequency and minimum TTC vary with travel speed.
The characterization of overtaking maneuvers from this study will aid in
improving the overall effectiveness of FCW systems by providing active safety
system designers with further understanding of driver action in overtaking
maneuvers, thereby increasing system warning accuracy, reducing erroneous
warnings, and improving driver acceptance.
PMID- 26436230
TI - Analysis of Driver Evasive Maneuvering Prior to Intersection Crashes Using Event
Data Recorders.
AB - OBJECTIVE: Intersection crashes account for over 4,500 fatalities in the United
States each year. Intersection Advanced Driver Assistance Systems (I-ADAS) are
emerging vehicle-based active safety systems that have the potential to help
drivers safely navigate across intersections and prevent intersection crashes and
injuries. The performance of an I-ADAS is expected to be highly dependent upon
driver evasive maneuvering prior to an intersection crash. Little has been
published, however, on the detailed evasive kinematics followed by drivers prior
to real-world intersection crashes. The objective of this study was to
characterize the frequency, timing, and kinematics of driver evasive maneuvers
prior to intersection crashes. METHODS: Event data recorders (EDRs) downloaded
from vehicles involved in intersection crashes were investigated as part of NASS
CDS years 2001 to 2013. A total of 135 EDRs with precrash vehicle speed and
braking application were downloaded to investigate evasive braking. A smaller
subset of 59 EDRs that collected vehicle yaw rate was additionally analyzed to
investigate evasive steering. Each vehicle was assigned to one of 3 precrash
movement classifiers (traveling through the intersection, completely stopped, or
rolling stop) based on the vehicle's calculated acceleration and observed
velocity profile. To ensure that any significant steering input observed was an
attempted evasive maneuver, the analysis excluded vehicles at intersections that
were turning, driving on a curved road, or performing a lane change. Braking
application at the last EDR-recorded time point was assumed to indicate evasive
braking. A vehicle yaw rate greater than 4 degrees per second was assumed to
indicate an evasive steering maneuver. RESULTS: Drivers executed crash avoidance
maneuvers in four-fifths of intersection crashes. A more detailed analysis of
evasive braking frequency by precrash maneuver revealed that drivers performing
complete or rolling stops (61.3%) braked less often than drivers traveling
through the intersection without yielding (79.0%). After accounting for
uncertainty in the timing of braking and steering data, the median evasive
braking time was found to be between 0.5 to 1.5 s prior to impact, and the median
initial evasive steering time was found to occur between 0.5 and 0.9 s prior to
impact. The median average evasive braking deceleration for all cases was found
to be 0.58 g. The median of the maximum evasive vehicle yaw rates was found to be
8.2 degrees per second. Evasive steering direction was found to be most
frequently in the direction of travel of the approaching vehicle. CONCLUSIONS:
The majority of drivers involved in intersection crashes were alert enough to
perform an evasive action. Most drivers used a combination of steering and
braking to avoid a crash. The average driver attempted to steer and brake at
approximately the same time prior to the crash.
PMID- 26436231
TI - On-Scene Injury Severity Prediction (OSISP) Algorithm for Truck Occupants.
AB - OBJECTIVE: The aim of this study is to develop an on-scene injury severity
prediction (OSISP) algorithm for truck occupants using only accident
characteristics that are feasible to assess at the scene of the accident. The
purpose of developing this algorithm is to use it as a basis for a field triage
tool used in traffic accidents involving trucks. In addition, the model can be
valuable for recognizing important factors for improving triage protocols used in
Sweden and possibly in other countries with similar traffic environments and
prehospital procedures. METHODS: The scope is adult truck occupants involved in
traffic accidents on Swedish public roads registered in the Swedish Traffic
Accident Data Acquisition (STRADA) database for calendar years 2003 to 2013.
STRADA contains information reported by the police and medical data on injured
road users treated at emergency hospitals. Using data from STRADA, 2 OSISP
multivariate logistic regression models for deriving the probability of severe
injury (defined here as having an Injury Severity Score [ISS] > 15) were
implemented for light and heavy trucks; that is, trucks with weight up to 3,500
kg and ? 16,500 kg, respectively. A 10-fold cross-validation procedure was used
to estimate the performance of the OSISP algorithm in terms of the area under the
receiver operating characteristic curve (AUC). RESULTS: The rate of belt use was
low, especially for heavy truck occupants. The OSISP models developed for light
and heavy trucks achieved cross-validation AUC of 0.81 and 0.74, respectively.
The AUC values obtained when the models were evaluated on all data without cross
validation were 0.87 for both light and heavy trucks. The difference in the AUC
values with and without use of cross-validation indicates overfitting of the
model, which may be a consequence of relatively small data sets. Belt use stands
out as the most valuable predictor in both types of trucks; accident type and age
are important predictors for light trucks. CONCLUSIONS: The OSISP models achieve
good discriminating capability for light truck occupants and a reasonable
performance for heavy truck occupants. The prediction accuracy may be increased
by acquiring more data. Belt use was the strongest predictor of severe injury for
both light and heavy truck occupants. There is a need for behavior-based safety
programs and/or other means to encourage truck occupants to always wear a seat
belt.
PMID- 26436232
TI - New Methodology for an Expert-Designed Map From International Classification of
Diseases (ICD) to Abbreviated Injury Scale (AIS) 3+ Severity Injury.
AB - OBJECTIVE: There has been a longstanding desire for a map to convert
International Classification of Diseases (ICD) injury codes to Abbreviated Injury
Scale (AIS) codes to reflect the severity of those diagnoses. The Association for
the Advancement of Automotive Medicine (AAAM) was tasked by European Union
representatives to create a categorical map classifying diagnoses codes as
serious injury (Abbreviated Injury Scale [AIS] 3+), minor/moderate injury (AIS
1/2), or indeterminate. This study's objective was to map injury-related ICD-9-CM
(clinical modification) and ICD-10-CM codes to these severity categories.
METHODS: Approximately 19,000 ICD codes were mapped, including injuries from the
following categories: amputations, blood vessel injury, burns, crushing injury,
dislocations/sprains/strains, foreign body, fractures, internal organ,
nerve/spinal cord injury, intracranial, laceration, open wounds, and superficial
injury/contusion. Two parallel activities were completed to create the maps: (1)
An in-person expert panel and (2) an electronic survey. The panel consisted of
expert users of AIS and ICD from North America, the United Kingdom, and
Australia. The panel met in person for 5 days, with follow-up virtual meetings to
create and revise the maps. Additional qualitative data were documented to
resolve potential discrepancies in mapping. The electronic survey was completed
by 95 injury coding professionals from North America, Spain, Australia, and New
Zealand over 12 weeks. ICD-to-AIS maps were created for: ICD-9-CM and ICD-10-CM.
Both maps indicated whether the corresponding AIS 2005/Update 2008 severity score
for each ICD code was AIS 3+, 1/2, or indeterminable. Though some ICD codes could
be mapped to multiple AIS codes, the maximum severity of all potentially mapped
injuries determined the final severity categorization. RESULTS: The in-person
panel consisted of 13 experts, with 11 Certified AIS specialists (CAISS) with a
median of 8 years and an average of 15 years of coding experience. Consensus was
reached for AIS severity categorization for all injury-related ICD codes. There
were 95 survey respondents, with a median of 8 years of injury coding experience.
Approximately 15 survey responses were collected per ICD code. Results from the 2
activities were compared, and any discrepancies were resolved using additional
qualitative and quantitative data from the in-person panel and survey results,
respectively. CONCLUSIONS: Robust maps of ICD-9-CM and ICD-10-CM injury codes to
AIS severity categories (3+ versus <3) were successfully created from an in
person panel discussion and electronic survey. These maps provide a link between
the common ICD diagnostic lexicons and the AIS severity coding system and are of
value to injury researchers, public health scientists, and epidemiologists using
large databases without available AIS coding.
PMID- 26436233
TI - Mortality Risk in Pediatric Motor Vehicle Crash Occupants: Accounting for
Developmental Stage and Challenging Abbreviated Injury Scale Metrics.
AB - OBJECTIVE: Survival risk ratios (SRRs) and their probabilistic counterpart,
mortality risk ratios (MRRs), have been shown to be at odds with Abbreviated
Injury Scale (AIS) severity scores for particular injuries in adults. SRRs have
been validated for pediatrics but have not been studied within the context of
pediatric age stratifications. We hypothesized that children with similar motor
vehicle crash (MVC) injuries may have different mortality risks (MR) based upon
developmental stage and that these MRs may not correlate with AIS severity.
METHODS: The NASS-CDS 2000-2011 was used to define the top 95% most common AIS 2+
injuries among MVC occupants in 4 age groups: 0-4, 5-9, 10-14, and 15-18 years.
Next, the National Trauma Databank 2002-2011 was used to calculate the MR
(proportion of those dying with an injury to those sustaining the injury) and the
co-injury-adjusted MR (MRMAIS) for each injury within 6 age groups: 0-4, 5-9, 10
14, 15-18, 0-18, and 19+ years. MR differences were evaluated between age groups
aggregately, between age groups based upon anatomic injury patterns and between
age groups on an individual injury level using nonparametric Wilcoxon tests and
chi-square or Fisher's exact tests as appropriate. Correlation between AIS and MR
within each age group was also evaluated. RESULTS: MR and MRMAIS distributions of
the most common AIS 2+ injuries were right skewed. Aggregate MR of these most
common injuries varied between the age groups, with 5- to 9-year-old and 10- to
14-year-old children having the lowest MRs and 0- to 4-year-old and 15- to 18
year-old children and adults having the highest MRs (all P <.05). Head and
thoracic injuries imparted the greatest mortality risk in all age groups with
median MRMAIS ranging from 0 to 6% and 0 to 4.5%, respectively. Injuries to
particular body regions also varied with respect to MR based upon age. For
example, thoracic injuries in adults had significantly higher MRMAIS than such
injuries among 5- to 9-year-olds and 10- to 14-year-olds (P =.04; P <.01).
Furthermore, though AIS was positively correlated with MR within each age group,
less correlation was seen for children than for adults. Large MR variations were
seen within each AIS grade, with some lower AIS severity injuries demonstrating
greater MRs than higher AIS severity injuries. As an example, MRMAIS in 0- to 18
year-olds was 0.4% for an AIS 3 radius fracture versus 1.4% for an AIS 2 vault
fracture. CONCLUSIONS: Trauma severity metrics are important for outcome
prediction models and can be used in pediatric triage algorithms and other injury
research. Trauma severity may vary for similar injuries based upon developmental
stage, and this difference should be reflected in severity metrics. The MR-based
data-driven determination of injury severity in pediatric occupants of different
age cohorts provides a supplement or an alternative to AIS severity
classification for pediatric occupants in MVCs.
PMID- 26436234
TI - Constrained Laboratory vs. Unconstrained Steering-Induced Rollover Crash Tests.
AB - OBJECTIVE: The goal of this study was to evaluate how well an in-laboratory
rollover crash test methodology that constrains vehicle motion can reproduce the
dynamics of unconstrained full-scale steering-induced rollover crash tests in
sand. METHODS: Data from previously-published unconstrained steering-induced
rollover crash tests using a full-size pickup and mid-sized sedan were analyzed
to determine vehicle-to-ground impact conditions and kinematic response of the
vehicles throughout the tests. Then, a pair of replicate vehicles were prepared
to match the inertial properties of the steering-induced test vehicles and
configured to record dynamic roof structure deformations and kinematic response.
RESULTS: Both vehicles experienced greater increases in roll-axis angular
velocities in the unconstrained tests than in the constrained tests; however, the
increases that occurred during the trailing side roof interaction were nearly
identical between tests for both vehicles. Both vehicles experienced linear
accelerations in the constrained tests that were similar to those in the
unconstrained tests, but the pickup, in particular, had accelerations that were
matched in magnitude, timing, and duration very closely between the two test
types. Deformations in the truck test were higher in the constrained than the
unconstrained, and deformations in the sedan were greater in the unconstrained
than the constrained as a result of constraints of the test fixture, and
differences in impact velocity for the trailing side. CONCLUSIONS: The results of
the current study suggest that in-laboratory rollover tests can be used to
simulate the injury-causing portions of unconstrained rollover crashes. To date,
such a demonstration has not yet been published in the open literature. This
study did, however, show that road surface can affect vehicle response in a way
that may not be able to be mimicked in the laboratory. Lastly, this study showed
that configuring the in-laboratory tests to match the leading-side touchdown
conditions could result in differences in the trailing side impact conditions.
PMID- 26436235
TI - Assessment of Bilateral Thoracic Loading on the Near-Side Occupant Due to
Occupant-to-Occupant Interaction in Vehicle Crash Tests.
AB - OBJECTIVE: This study aims, by means of the WorldSID 50th percentile male, to
evaluate thoracic loading and injury risk to the near-side occupant due to
occupant-to-occupant interaction in combination with loading from an intruding
structure. METHOD: Nine vehicle crash tests were performed with a 50th percentile
WorldSID male dummy in the near-side (adjacent to the intruding structure) seat
and a THOR or ES2 dummy in the far-side (opposite the intruding structure) seat.
The near-side seated WorldSID was equipped with 6 + 6 IR-Traccs (LH and RH) in
the thorax/abdomen enabling measurement of bilateral deflection. To differentiate
deflection caused by the intrusion, and the deflection caused by the neighboring
occupant, time history curves were analyzed. The crash tests were performed with
different modern vehicles, equipped with thorax side airbags and inflatable
curtains, ranging from a compact car to a large sedan, and in different loading
conditions such as car-to-car, barrier, and pole tests. Lateral delta V based on
vehicle tunnel acceleration and maximum residual intrusion at occupant position
were used as a measurement of crash severity to compare injury measurements.
RESULT: In the 9 vehicle crash tests, thoracic loading, induced by the intruding
structure as well as from the far-side occupant, varied due to the size and
structural performance of the car as well as the severity of the crash. Peak
deflection on the thoracic outboard side occurred during the first 50 ms of the
event. Between 70 to 150 ms loading induced by the neighboring occupant occurred
and resulted in an inboard-side peak deflection and viscous criterion. In the
tests where the target vehicle lateral delta V was below 30 km/h and intrusion
less than 200 mm, deflections were low on both the outboard (20-40 mm) and
inboard side (10-15 mm). At higher crash severities, delta V 35 km/h and above as
well as intrusions larger than 350 mm, the inboard deflections (caused by
interaction to the far-side occupant) were of the same magnitude or even higher
(30-70 mm) than the outboard deflections (30-50 mm). CONCLUSION: A WorldSID 50th
percentile male equipped with bilateral IR-Traccs can detect loading to the
thorax from a neighboring occupant making injury risk assessment feasible for
this type of loading. At crash severities resulting in a delta V above 35 km/h
and intrusions larger than 350 mm, both the inboard deflection and VC resulted in
high risks of Abbreviated Injury Scale (AIS) 3+ injury, especially for a senior
occupant.
PMID- 26436237
TI - Short Communications from AAAM's 59th Annual Scientific Conference.
PMID- 26436236
TI - Injuries in Full-Scale Vehicle Side Impact Moving Deformable Barrier and Pole
Tests Using Postmortem Human Subjects.
AB - OBJECTIVE: To conduct near-side moving deformable barrier (MDB) and pole tests
with postmortem human subjects (PMHS) in full-scale modern vehicles, document and
score injuries, and examine the potential for angled chest loading in these tests
to serve as a data set for dummy biofidelity evaluations and computational
modeling. METHODS: Two PMHS (outboard left front and rear seat occupants) for MDB
and one PMHS (outboard left front seat occupant) for pole tests were used. Both
tests used sedan-type vehicles from same manufacturer with side airbags. Pretest
x-ray and computed tomography (CT) images were obtained. Three-point belt
restrained surrogates were positioned in respective outboard seats.
Accelerometers were secured to T1, T6, and T12 spines; sternum and pelvis; seat
tracks; floor; center of gravity; and MDB. Load cells were used on the pole.
Biomechanical data were gathered at 20 kHz. Outboard and inboard high-speed
cameras were used for kinematics. X-rays and CT images were taken and autopsy was
done following the test. The Abbreviated Injury Scale (AIS) 2005 scoring scheme
was used to score injuries. RESULTS: MDB test: male (front seat) and female (rear
seat) PMHS occupant demographics: 52 and 57 years, 177 and 166 cm stature, 78 and
65 kg total body mass. Demographics of the PMHS occupant in the pole test: male,
26 years, 179 cm stature, and 84 kg total body mass. Front seat PMHS in MDB test:
6 near-side rib fractures (AIS = 3): 160-265 mm vertically from suprasternal
notch and 40-80 mm circumferentially from center of sternum. Left rear seat PMHS
responded with multiple bilateral rib fractures: 9 on the near side and 5 on the
contralateral side (AIS = 3). One rib fractured twice. On the near and
contralateral sides, fractures were 30-210 and 20-105 mm vertically from the
suprasternal notch and 90-200 and 55-135 mm circumferentially from the center of
sternum. A fracture of the left intertrochanteric crest occurred (AIS = 3). Pole
test PMHS had one near-side third rib fracture. Thoracic accelerations of the 2
occupants were different in the MDB test. Though both occupants sustained
positive and negative x-accelerations to the sternum, peak magnitudes and
relative changes were greater for the rear than the front seat occupant.
Magnitudes of the thoracic and sternum accelerations were lower in the pole test.
CONCLUSIONS: This is the first study to use PMHS occupants in MDB and pole tests
in the same recent model year vehicles with side airbag and head curtain
restraints. Injuries to the unilateral thorax for the front seat PMHS in contrast
to the bilateral thorax and hip for the rear seat occupant in the MDB test
indicate the effects of impact on the seating location and restraint system.
Posterolateral locations of fractures to the front seat PMHS are attributed to
constrained kinematics of occupant interaction with torso side airbag restraint
system. Angled loading to the rear seat occupant from coupled sagittal and
coronal accelerations of the sternum representing anterior thorax loading
contributed to bilateral fractures. Inward bending initiated by the distal femur
complex resulting in adduction of ipsilateral lower extremity resulted in
intertrochanteric fracture to the rear seat occupant. These results serve as a
data set for evaluating the biofidelity of the WorldSID and federalized side
impact dummies and assist in validating human body computational models, which
are increasingly used in crashworthiness studies.
PMID- 26436238
TI - Evaluating the Effect of a Mechanical Adjunct to Improve the Installation of
Child Restraint Systems to Vehicles.
AB - OBJECTIVES: We explored if an alternative CRS design that utilized a mechanical
adjunct to amplify the force applied to the adult seat belt (intervention CRS)
results in more accurate and secure attachment between the CRS and the vehicle
compared to similar CRS models that use LATCH or the existing adult seat belt. We
conducted three separate studies to address this question and additionally
explored: (1) the contribution of prior CRS installation experience (Study 1),
(2) the value-added of CRS labeling (Study 2), and (3) paper-based vs. video
instructions (Study 3). METHODS: In Studies 1 and 2 we assessed a forward facing
combination CRS design (intervention CRS) compared to a commercially available
LATCH equipped model (control CRS) and in Study 3 we conducted a similar study
using a convertible model of both the intervention and control CRS. Participants
installed both CRS in a contemporary minivan and could choose which type of
attachment to use for the control CRS (LATCH or seat belt); order of installation
was counter-balanced. Evaluators systematically examined installations for
accuracy and security. RESULTS: Study 1: A greater proportion of participants in
both the experienced and inexperienced groups was able to securely install the
intervention CRS compared to the control CRS: (45% vs. 16%, p =.0001 for
experienced) and (37% vs. 6%, p =.003 for inexperienced). No differences between
the CRS were observed for accuracy of installation in either user group. Study 2:
A greater proportion of participants were able to securely install the enhanced
intervention CRS compared to the control CRS: (62% vs. 9%, p =.001). The
intervention CRS demonstrated reduced installation accuracy: (30% vs. 61%, p
=.001). Study 3: A greater proportion of participants was able to securely
install the intervention CRS compared to the control CRS: 79% vs. 66% p =.03, but
this effect was smaller than in the previous studies. Participants were less
likely to achieve an accurate installation with the intervention CRS compared to
the control CRS: 54% vs. 79%, p =.004. Common accuracy errors in each study
included twisting or misrouting the seatbelt when installing the intervention
CRS. CONCLUSIONS: Our results suggest that novel CRS designs that utilize
mechanical advantage to facilitate attachment of the CRS to the vehicle result in
a tighter installation compared to LATCH equipped models, but an increase in
accuracy errors occurred.
PMID- 26436240
TI - Did Child Restraint Laws Globally Converge? Examining 40 Years of Policy
Diffusion.
AB - OBJECTIVE: The objective of the current study is to determine what factors have
been associated with the global adoption of mandatory child restraint laws
(ChRLs) since 1975. METHODS: In order to determine what factors explained the
global adoption of mandatory ChRLs, Weibull models were analyzed. To carry out
this analysis, 170 countries were considered and the time risk corresponded to
5,146 observations for the period 1957-2013. The dependent variable was first
time to adopt a ChRL. Independent variables representing global factors were the
World Health Organization (WHO) and World Bank's (WB) road safety global
campaign; the Geneva Convention on Road Traffic; and the United Nation's (UN)
1958 Vehicle Agreement. Independent variables representing regional factors were
the creation of the European Transport Safety Council and being a Commonwealth
country. Independent variables representing national factors were population;
gross domestic product (GDP) per capita; political violence; existence of road
safety nongovernmental organizations (NGOs); and existence of road safety
agencies. Urbanization served as a control variable. To examine regional
dynamics, Weibull models for Africa, Asia, Europe, North America, Latin America,
the Caribbean, and the Commonwealth were also carried out. RESULTS: Empirical
estimates from full Weibull models suggest that 2 global factors and 2 national
factors are significantly associated with the adoption of this measure. The
global factors explaining adoption are the WHO and WB's road safety global
campaign implemented after 2004 (P <.01), and the UN's 1958 Vehicle Agreement (P
<.001). National factors were GDP (P <.01) and existence of road safety agencies
(P <.05). The time parameter rho for the full Weibull model was 1.425 (P <.001),
suggesting that the likelihood of ChRL adoption increased over the observed
period of time, confirming that the diffusion of this policy was global. Regional
analysis showed that the UN's Convention on Road Traffic was significant in Asia,
the creation of the European Transport Safety Council was significant in Europe
and North America, and the global campaign was in Africa. In Commonwealth and
European and North American countries, the existence of road safety agencies was
also positively associated with ChRL adoption. CONCLUSIONS: Results of the world
models suggest that the WHO and WB's global road safety campaign was effective in
disseminating ChRLs after 2004. Furthermore, regions such as Asia and Europe and
North America were early adopters since specific regional and national
characteristics anticipated the introduction of this policy before 2004. In this
particular case, the creation of the European Transport Safety Council was
fundamental in promoting ChRLs. Thus, in order to introduce conditions to more
rapidly diffuse road safety measures across lagging regions, the maintenance of
global efforts and the creation of road safety regional organizations should be
encouraged. Lastly, the case of ChRL convergence illustrates how mechanisms of
global and regional diffusion need to be analytically differentiated in order
better to assess the process of policy diffusion.
PMID- 26436241
TI - Reasons for Child Passenger Nonrestraint in Motor Vehicles.
AB - OBJECTIVE: Although child passenger restraint use in motor vehicles has
increased, there is an important minority of children who remain unrestrained.
The goal of this study was to identify the frequency of and under what
circumstances parents keep their children unrestrained. METHODS: A cross
sectional, online survey was distributed to parents and caregivers of children 10
years old and younger. Survey participants were asked about child restraint
practices, including frequency of and reasons for nonuse of restraints. Parents
were specifically asked how acceptable it would be to keep their child
unrestrained in certain situations. RESULTS: One thousand two hundred eighty-five
parents and guardians responded to the survey and 1,002 completed it; 23.8% (95%
confidence interval [CI], 21.3-26.6%) of respondents said they had driven with
their child not fully restrained on at least one occasion. Approximately 1 in 5
parents strongly or somewhat agreed that it would be acceptable to keep their
child unrestrained in certain situations, including a short drive, in a rush, an
inadequate number of restraints, riding in a taxi, if somebody was holding the
child, and as a reward for a child. Parents were more likely to agree that it was
acceptable to keep their child unrestrained under nearly all circumstances listed
if they were male, ages 18-29, with a graduate school education, in the $100,000+
income bracket, or Latino. CONCLUSIONS: There are certain situations for which
parents find it acceptable to leave their children unrestrained. This has
implications for targeted child passenger safety efforts designed to maximize
consistent restraint use.
PMID- 26436242
TI - Children's and Adults' Comfort Experience of Extra Seat Belts When Riding in the
Rear Seat of a Passenger Car.
AB - OBJECTIVE: The objective of this study was to explore passengers' comfort
experience of extra seat belts during on-road driving in the rear seat of a
passenger car and to investigate how the use of extra belts affects children's
and adults' attitudes to the product. METHODS: Two different seat belt systems
were tested, criss-cross (CC) and backpack (BP), consisting of the standard 3
point belt together with an additional 2-point belt. In total, 32 participants
(15 children aged 6-10, 6 youths aged 11-15, and 11 adults aged 20-79, who
differed considerably in size, shape, and proportions) traveled for one hour with
each system, including city traffic and highway driving. Four video cameras
monitored the test subject during the drive. Subjective data regarding emotions
and perceived discomfort were collected in questionnaires every 20 min. A
semistructured interview was held afterwards. RESULTS: All participant groups
accepted the new products and especially the increased feeling of safety (P
<.01); 56% preferred CC and 44% preferred BP but the difference was not
significant. In total, 81% wanted to have extra seat belts in their family car.
CC was appreciated for its symmetry, comfort, and the perceived feeling of
safety. Some participants found CC unpleasant because the belts tended to slip
close to the neck, described as a strangling feeling. BP was simpler to use and
did not cause annoyance to the neck in the way CC did. Instead, it felt
asymmetric and to some extent less safe than CC. Body size and shape affected
seat belt fit to a great extent, which in turn affected the experience of
comfort, both initially and over time. Perceived safety benefit and experienced
comfort were the most determinant factors for the attitude toward the extra seat
belts. The extra seat belts were perceived as being better than the participants
had expected before the test, and they became more used to them over time.
CONCLUSION: This exploratory study provided valuable knowledge from a user
perspective for further development of new seat belt systems in cars. In addition
to an increased feeling of safety, seat belt fit and comfort are supplementary
influencing factors when it comes to gaining acceptance of new seat belt systems.
PMID- 26436243
TI - Teen Drivers' Perceptions of Inattention and Cell Phone Use While Driving.
AB - OBJECTIVE: Inattention to the roadway, including cell phone use while driving
(cell phone calls, sending and reading texts, mobile app use, and Internet use),
is a critical problem for teen drivers and increases risk for crashes. Effective
behavioral interventions for teens are needed in order to decrease teen driver
inattention related to cell phone use while driving. However, teens' perceptions
of mobile device use while driving is a necessary component for theoretically
driven behavior change interventions. The purpose of this study was to describe
teen drivers' perceptions of cell phone use while driving in order to inform
future interventions to reduce risky driving. METHODS: We conducted 7 focus
groups with a total of 30 teen drivers, ages 16-18, licensed for <= 1 year in
Pennsylvania. The focus group interview guide and analysis were based on the
Theory of Planned Behavior, identifying the attitudes, perceived behavioral
control, and norms about inattention to the roadway. Directed descriptive content
analysis was used to analyze the focus group interviews. All focus groups were
coded by 2 research team members and discrepancies were reconciled. Themes were
developed based on the data. RESULTS: Teens had a mean age of 17.39 (SD = 0.52),
mean length of licensure of 173.7 days (SD = 109.2; range 4-364), were 50% male
and predominately white (90%) and non-Hispanic (97%). From the focus group data,
3 major themes emerged: (1) Recognizing the danger but still engaging; (2)
Considering context; and (3) Formulating safer behaviors that might reduce risk.
Despite recognizing that handheld cell phone use, texting, and social media app
use are dangerous and distracting while driving, teens and their peers often
engaged in these behaviors. Teens described how the context of the situation
contributed to whether a teen would place or answer a call, write or respond to a
text, or use a social media app. Teens identified ways in which they controlled
their behaviors, although some still drew attention away from the roadway.
CONCLUSIONS: Cell phone use while driving is a contributor to motor vehicle
crashes in teens, and effective interventions to decrease risks are needed. Teens
viewed some types of cell phone use as unsafe and describe methods in which they
control their behaviors. However, some of their methods still take attention off
the primary task of driving. Teens could benefit from behavior change
interventions that propose strategies to promote focused attention on the roadway
at all times during the driving trip.
PMID- 26436245
TI - An Analysis of Young Driver Crash Types and the Associated Lifetime Care Cost in
Victoria, Australia.
AB - OBJECTIVE: The elevated crash involvement rate of young drivers is well
documented. Given the higher crash risk of young drivers and the need for
innovative policy and programs, it remains important to fully understand the type
of crashes young drivers are involved in, and knowledge of the lifetime care cost
of crashes can support effective policy development. The aim of this article is
to document the number and type of young driver crashes, as well as the
associated lifetime care cost over a 9-year period (2005-2013) in Victoria,
Australia. METHODS: In Victoria, Australia, the Transport Accident Commission
(TAC) has legislated responsibility for road safety and the care of persons
injured in road crashes, irrespective of fault. TAC claims data for the period
2005-2013 were used to document the number and type of young driver crashes.
Lifetime care costs (past and future payment liabilities) were calculated by
Taylor Fry actuarial consultancy. License and population data were used to define
the crash involvement rate of young drivers. RESULTS: Over the 9-year period,
16,817 claims were lodged to the TAC by drivers 18-25 years of age following a
crash. There were 646 fewer drivers aged 18-25 killed and injured in 2013,
compared to 2005, representing an unadjusted change of -28.7% (-29.8% males;
28.4% females). The total lifetime care cost of young drivers killed and injured
in Victoria for the period 2005-2013 was estimated to be AU$634 million (US$493
million). Differences between males and females, single- and multivehicle
crashes, and fatalities and injuries were found to be statistically significant.
Run-off-road crashes and crashes from opposing direction were overrepresented in
the lifetime care costs for young driver claimants. Twenty-eight injured drivers
were classified as high-severity claims. These 28 claimants require additional
long-term care, which was estimated to be AU$219 million; of these 28, 24 were
male (85.7%). The long-term care costs for these 28 drivers (0.16%) accounts for
34.5% of the total lifetime care cost of all 18- to 25-year-old injured drivers.
CONCLUSIONS: By using no-fault lifetime care costs that account for medical and
like expenses, rehabilitation, and social reintegration costs, a more accurate
understanding of the cost of young driver crashes can be determined. Application
of these costs to specific crash types highlights new priorities and
opportunities for developing programs to reduce young driver crashes.
PMID- 26436244
TI - Effects of Dram Shop, Responsible Beverage Service Training, and State Alcohol
Control Laws on Underage Drinking Driver Fatal Crash Ratios.
AB - OBJECTIVES: In this study, we aimed to determine whether three minimum legal
drinking age 21 (MLDA-21) laws-dram shop liability, responsible beverage service
(RBS) training, and state control of alcohol sales-have had an impact on underage
drinking and driving fatal crashes using annual state-level data, and compared
states with strong laws to those with weak laws to examine their effect on beer
consumption and fatal crash ratios. METHODS: Using the Fatality Analysis
Reporting System, we calculated the ratio of drinking to nondrinking drivers
under age 21 involved in fatal crashes as our key outcome measure. We used
structural equation modeling to evaluate the three MLDA-21 laws. We controlled
for covariates known to impact fatal crashes including: 17 additional MLDA-21
laws; administrative license revocation; blood alcohol concentration limits of.08
and.10 for driving; seat belt laws; sobriety checkpoint frequency; unemployment
rates; and vehicle miles traveled. Outcome variables, in addition to the fatal
crash ratios of drinking to nondrinking drivers under age 21 included state per
capita beer consumption. RESULTS: Dram shop liability laws were associated with a
2.4% total effect decrease (direct effects: beta =.019, p =.018). Similarly, RBS
training laws were associated with a 3.6% total effect decrease (direct effect:
beta =.048, p =.001) in the ratio of drinking to nondrinking drivers under age 21
involved in fatal crashes. There was a significant relationship between dram shop
liability law strength and per capita beer consumption, F (4, 1528) = 24.32, p
<.001, partial eta(2) =.016, showing states with strong dram shop liability laws
(Mean (M) = 1.276) averaging significantly lower per capita beer consumption than
states with weak laws (M = 1.340). CONCLUSIONS: Dram shop liability laws and RBS
laws were both associated with significantly reduced per capita beer consumption
and fatal crash ratios. In practical terms, this means that dram shop liability
laws are currently associated with saving an estimated 64 lives in the 45
jurisdictions that currently have the law. If the remaining 6 states adopted the
dram shop law, an additional 9 lives could potentially be saved annually.
Similarly, RBS training laws are associated with saving an estimated 83 lives in
the 37 jurisdictions that currently have the laws. If the remaining 14 states
adopted these RBS training laws, we estimate that an additional 28 lives could
potentially be saved.
PMID- 26436246
TI - Improving the Chest Protection of Elderly Occupants in Frontal Crashes Using
SMART Load Limiters.
AB - OBJECTIVE: To determine whether varying the seat belt load limiter (SBL)
according to crash and occupant characteristics could have real-world injury
reduction benefits in frontal impacts and, if so, to quantify those benefits.
METHODS: Real-world UK accident data were used to identify the target population
of vehicle occupants and frontal crash scenarios where improved chest protection
could be most beneficial. Generic baseline driver and front passenger numerical
models using a 50th percentile dummy were developed with MADYMO software.
Simulations were performed where the load limiter threshold was varied in
selected frontal impact scenarios. For each SBL setting, restraint performance,
dummy kinematics, and injury outcome were studied in 5 different frontal impact
types. Thoracic injury predictions were converted into injury probability values
using Abbreviated Injury Scale (AIS) 2+ age-dependent thoracic risk curves
developed and validated based on a methodology proposed by Laituri et al. (2005).
Real-world benefit was quantified using the predicted AIS 2+ risk and assuming
that an appropriate adaptive system was fitted to all the cars in a real-world
sample of recent frontal crashes involving European passenger cars. RESULTS: From
the accident data sample the chest was the most frequently injured body region at
an AIS 2+ level in frontal impacts (7% of front seat occupants). The proportion
of older vehicle front seat occupants (>64 years) with AIS 2+ injury was also
greater than the proportion of younger occupants. Additionally, older occupants
were more likely to sustain seat belt-induced serious chest injury in low- and
moderate-speed frontal crashes. In both front seating positions, the low SBL
provided the best chest injury protection, without increasing the risk to other
body regions. In severe impacts, the low SBL allowed the driver to move
dangerously close to the steering wheel. Compared to the driver side, greater
ride-down space on the passenger side gave a higher potential for using the low
SBLs. When applying the AIS 2+ risk reduction findings to the weighted accident
data sample, the risk of sustaining an AIS 2+ seat belt injury changed to 0.9,
4.9, and 8.1% for young, mid, and older occupants, respectively, from their
actual injury risk of 1.3, 7.6, and 13.1%. CONCLUSIONS: These results suggest the
potential for improving the safety of older occupants with the development of
smarter restraint systems. This is an important finding because the number of
older users is expected to increase rapidly over the next 20 years. The greatest
benefits were seen at lower crash severities. This is also important because most
real-world crashes occur at lower speeds.
PMID- 26436247
TI - The Contribution of Pre-impact Posture on Restrained Occupant Finite Element
Model Response in Frontal Impact.
AB - OBJECTIVE: The objective of this study was to discuss the influence of the pre
impact posture to the response of a finite element human body model (HBM) in
frontal impacts. METHODS: This study uses previously published cadaveric tests
(PMHS), which measured six realistic pre-impact postures. Seven postured models
were created from the THUMS occupant model (v4.0): one matching the standard
UMTRI driving posture as it was the target posture in the experiments, and six
matching the measured pre-impact postures. The same measurements as those
obtained during the cadaveric tests were calculated from the simulations, and
biofidelity metrics based on signals correlation (CORA) were established to
compare the response of the seven models to the experiments. RESULTS: The HBM
responses showed good agreement with the PMHS responses for the reaction forces
(CORA = 0.80 +/- 0.05) and the kinematics of the lower part of the torso but only
fair correlation was found with the head, the upper spine, rib strains (CORA=
0.50 +/- 0.05) and chest deflections (CORA = 0.67 +/- 0.08). All models sustained
rib fractures, sternal fracture and clavicle fracture. The average number of rib
fractures for all the models was 5.3 +/- 1.0, lower than in the experiments (10.8
+/- 9.0). Variation in pre-impact posture greatly altered the time histories of
the reaction forces, deflections and the rib strains, mainly in terms of time
delay, but no definite improvement in HBM response or injury prediction was
observed. By modifying only the posture of the HBM, the variability in the impact
response was found to be equivalent to that observed in the experiments. The
postured HBM sustained from 4 to 8 rib fractures, confirming that the pre-impact
posture influenced the injury outcome predicted by the simulation. CONCLUSIONS:
This study tries to answer an important question: what is the effect of occupant
posture on kinematics and kinetics. Significant differences in kinematics
observed between HBM and PMHS suggesting more coupling between the pelvis and the
spine for the models which makes the model response very sensitive to any
variation in the spine posture. Consequently, the findings observed for the HBM
cannot be extended to PMHS. Besides, pre-impact posture should be carefully
quantified during experiments and the evaluation of HBM should take into account
the variation in the predicted impact response due to the variation in the model
posture.
PMID- 26436248
TI - The Influence of Enhanced Side Impact Protection on Kinematics and Injury
Measures of Far- or Center-Seated Children in Forward-Facing Child Restraints.
AB - OBJECTIVE: To evaluate the influence of forward-facing child restraint systems'
(FFCRSs) side impact structure, such as side wings, on the head kinematics and
response of a restrained, far- or center-seated 3-year-old anthropomorphic test
device (ATD) in oblique sled tests. METHODS: Sled tests were conducted utilizing
an FFCRS with large side wings and with the side wings removed. The CRS were
attached via LATCH on 2 different vehicle seat fixtures-a small SUV rear bench
seat and minivan rear bucket seat-secured to the sled carriage at 20 degrees
from lateral. Four tests were conducted on each vehicle seat fixture, 2 for each
FFCRS configuration. A Q3s dummy was positioned in FFCRS according to the CRS
owner's manual and FMVSS 213 procedures. The tests were conducted using the
proposed FMVSS 213 side impact pulse. Three-dimensional motion cameras collected
head excursion data. Relevant data collected during testing included the ATD head
excursions, head accelerations, LATCH belt loads, and neck loads. RESULTS:
Results indicate that side wings have little influence on head excursions and ATD
response. The median lateral head excursion was 435 mm with side wings and 443 mm
without side wings. The primary differences in head response were observed
between the 2 vehicle seat fixtures due to the vehicle seat head restraint
design. The bench seat integrated head restraint forced a tether routing path
over the head restraint. Due to the lateral crash forces, the tether moved
laterally off the head restraint reducing tension and increasing head excursion
(477 mm median). In contrast, when the tether was routed through the bucket
seat's adjustable head restraint, it maintained a tight attachment and helped
control head excursion (393 mm median). CONCLUSION: This testing illustrated
relevant side impact crash circumstances where side wings do not provide the
desired head containment for a 3-year-old ATD seated far-side or center in FFCRS.
The head appears to roll out of the FFCRS even in the presence of side wings,
which may expose the occupant to potential head impact injuries. We postulate
that in a center or far-side seating configuration, the absence of door structure
immediately adjacent to the CRS facilitates the rotation and tipping of the FFCRS
toward the impact side and the roll-out of the head around the side wing
structure. Results suggest that other prevention measures, in the form of
alternative side impact structure design, FFCRS vehicle attachment, or shared
protection between the FFCRS and the vehicle, may be necessary to protect
children in oblique side impact crashes.
PMID- 26436249
TI - Survival Model for Foot and Leg High Rate Axial Impact Injury Data.
AB - OBJECTIVES: Understanding how lower extremity injuries from automotive intrusion
and underbody blast (UBB) differ is of key importance when determining whether
automotive injury criteria can be applied to blast rate scenarios. This article
provides a review of existing injury risk analyses and outlines an approach to
improve injury prediction for an expanded range of loading rates. This analysis
will address issues with existing injury risk functions including inaccuracies
due to inertial and potential viscous resistance at higher loading rates.
METHODS: This survival analysis attempts to minimize these errors by considering
injury location statistics and a predictor variable selection process dependent
upon failure mechanisms of bone. Distribution of foot/ankle/leg injuries induced
by axial impact loading at rates characteristic of UBB as well as automotive
intrusion was studied and calcaneus injuries were found to be the most common
injury; thus, footplate force was chosen as the main predictor variable because
of its proximity to injury location to prevent inaccuracies associated with
inertial differences due to loading rate. A survival analysis was then performed
with age, sex, dorsiflexion angle, and mass as covariates. This statistical
analysis uses data from previous axial postmortem human surrogate (PMHS)
component leg tests to provide perspectives on how proximal boundary conditions
and loading rate affect injury probability in the foot/ankle/leg (n = 82).
RESULTS: Tibia force-at-fracture proved to be up to 20% inaccurate in previous
analyses because of viscous resistance and inertial effects within the data set
used, suggesting that previous injury criteria are accurate only for specific
rates of loading and boundary conditions. The statistical model presented in this
article predicts 50% probability of injury for a plantar force of 10.2 kN for a
50th percentile male with a neutral ankle position. Force rate was found to be an
insignificant covariate because of the limited range of loading rate differences
within the data set; however, compensation for inertial effects caused by
measuring the force-at-fracture in a location closer to expected injury location
improved the model's predictive capabilities for the entire data set.
CONCLUSIONS: This study provides better injury prediction capabilities for both
automotive and blast rates because of reduced sensitivity to inertial effects and
tibia-fibula load sharing. Further, a framework is provided for future injury
criteria generation for high rate loading scenarios. This analysis also suggests
key improvements to be made to existing anthropomorphic test device (ATD) lower
extremities to provide accurate injury prediction for high rate applications such
as UBB.
PMID- 26436251
TI - Microbial Transport and Fate in the Subsurface Environment: Introduction to the
Special Section.
AB - Microorganisms constitute an almost exclusive form of life in the earth's
subsurface environment (not including caves), particularly at depths exceeding
the soil horizon. While of broad interest to ecology and geology, scientific
interest in the fate and transport of microorganisms, particularly those
introduced through the anthropogenic environment, has focused on understanding
the subsurface environment as a pathway for human pathogens and on optimizing the
use of microbial organisms for remediation of potable groundwater. This special
section, inspired by the 2014 Ninth International Symposium for Subsurface
Microbiology, brings together recent efforts to better understand the
spatiotemporal occurrence of anthropogenic microbial groundwater contamination
and the fate and transport of microbes in the subsurface environment: in soils,
deep unsaturated zones, and within aquifer systems. Work includes field
reconnaissance, controlled laboratory studies to improve our understanding of
specific fate and transport processes, and the development and application of
improved mechanistic understanding of microbial fate and transport processes in
the subsurface environment. The findings confirm and also challenge the
limitations of our current understanding of highly complex microbial fate and
transport processes across spatiotemporal scales in the subsurface environment;
they also add to the increasing knowledge base to improve our ability to protect
drinking water resources and perform in situ environmental remediation.
PMID- 26436250
TI - Contractility Measurements on Isolated Papillary Muscles for the Investigation of
Cardiac Inotropy in Mice.
AB - Papillary muscle isolated from adult mouse hearts can be used to study cardiac
contractility during different physiological/pathological conditions. The
contractile characteristics can be evaluated independently of external influences
such as vascular tonus or neurohumoral status. It depicts a scientific approach
between single cell measurements with isolated cardiac myocytes and in vivo
studies like echocardiography. Thus, papillary muscle preparations serve as an
excellent model to study cardiac physiology/pathophysiology and can be used for
investigations like the modulation by pharmacological agents or the exploration
of transgenic animal models. Here, we describe a method of isolating the murine
left anterior papillary muscle to investigate cardiac contractility in an organ
bath setup. In contrast to a muscle strip preparation isolated from the
ventricular wall, the papillary muscle can be prepared in toto without damaging
the muscle tissue severely. The organ bath setup consists of several temperature
controlled, gassed and electrode-equipped organ bath chambers. The isolated
papillary muscle is fixed in the organ bath chamber and electrically stimulated.
The evoked twitch force is recorded using a pressure transducer and parameters
such as twitch force amplitude and twitch kinetics are analyzed. Different
experimental protocols can be performed to investigate the calcium- and frequency
dependent contractility as well as dose-response curves of contractile agents
such as catecholamines or other pharmaceuticals. Additionally, pathologic
conditions like acute ischemia can be simulated.
PMID- 26436252
TI - Release and Removal of Microorganisms from Land-Deposited Animal Waste and Animal
Manures: A Review of Data and Models.
AB - Microbial pathogens present a leading cause of impairment to rivers, bays, and
estuaries in the United States, and agriculture is often viewed as the major
contributor to such contamination. Microbial indicators and pathogens are
released from land-applied animal manure during precipitation and irrigation
events and are carried in overland and subsurface flow that can reach and
contaminate surface waters and ground water used for human recreation and food
production. Simulating the release and removal of manure-borne pathogens and
indicator microorganisms is an essential component of microbial fate and
transport modeling regarding food safety and water quality. Although microbial
release controls the quantities of available pathogens and indicators that move
toward human exposure, a literature review on this topic is lacking. This
critical review on microbial release and subsequent removal from manure and
animal waste application areas includes sections on microbial release processes
and release-affecting factors, such as differences in the release of microbial
species or groups; bacterial attachment in turbid suspensions; animal source;
animal waste composition; waste aging; manure application method; manure
treatment effect; rainfall intensity, duration, and energy; rainfall recurrence;
dissolved salts and temperature; vegetation and soil; and spatial and temporal
scale. Differences in microbial release from liquid and solid manures are
illustrated, and the influential processes are discussed. Models used for
simulating release and removal and current knowledge gaps are presented, and
avenues for future research are suggested.
PMID- 26436253
TI - Bacterial Pathogen Indicator Transport from Livestock Mortality Biopiles.
AB - Biopiles can be used to dispose of slaughterhouse residuals (SLRs); however, the
fate of pathogenic bacteria (e.g., pathogenic strains of , ) in these systems is
not well understood. The transport of these bacteria in water leaching from the
biopile could represent a significant contamination source. This research
examined the transport of Enterobacteriaceae and Enterococcaceae indicator
bacteria from SLR biopiles. Three biopiles (2.6 m wide by 4.6 m long by 1.8 m
high) were formed on soil layers in concrete cells that allowed for real-time
monitoring of environmental parameters, hydrologic flux, and indicator bacteria
levels in effluent leaching from the piles. In biopile effluent, indicator
bacteria populations decreased exponentially following biopile formation.
Indicator bacteria loads in effluent constituted <0.01% of the initial indicator
bacteria levels in the biopiles, which was attributed to retention, inactivation,
and death. Nearly 90% of the total indicator bacteria loads coincided with large
precipitation events (>15 mm d). Movement of the indicator bacteria through the
biopiles and underlying soil appeared to be consistent with preferential flow
phenomena. The populations of the Enterobacteriaceae indicators remained low in
conditions of higher soil water content and lower biopile temperatures, whereas
the Enterococcaceae indicator appeared to regrow in these conditions. This
indicated that bacterial pathogen transport from a biopile could be a concern
after the disappearance of conventional bacterial indicators, such as .
Management considerations should attempt to divert excess water from entering a
biopile, such as locating a biopile under a roof. Unsaturated biopile and soil
conditions should be maintained to impede water flow through preferential
pathways in the soil underneath a biopile.
PMID- 26436254
TI - Swimming Motility Reduces Deposition to Silica Surfaces.
AB - The transport and fate of bacteria in porous media is influenced by
physicochemical and biological properties. This study investigated the effect of
swimming motility on the attachment of cells to silica surfaces through
comprehensive analysis of cell deposition in model porous media. Distinct
motilities were quantified for different strains using global and cluster-based
statistical analyses of microscopic images taken under no-flow condition. The
wild-type, flagellated strain DJ showed strong swimming as a result of the
actively swimming subpopulation whose average speed was 25.6 MUm/s; the impaired
swimming of strain DJ77 was attributed to the lower average speed of 17.4 MUm/s
in its actively swimming subpopulation; and both the nonflagellated JZ52 and
chemically treated DJ cells were nonmotile. The approach and deposition of these
bacterial cells were analyzed in porous media setups, including single-collector
radial stagnation point flow cells (RSPF) and two-dimensional multiple-collector
micromodels under well-defined hydrodynamic conditions. In RSPF experiments, both
swimming and nonmotile cells moved with the flow when at a distance >=20 MUm
above the collector surface. Closer to the surface, DJ cells showed both
horizontal and vertical movement, limiting their contact with the surface, while
chemically treated DJ cells moved with the flow to reach the surface. These
results explain how wild-type swimming reduces attachment. In agreement, the
deposition in micromodels was also lowest for DJ compared with those for DJ77 and
JZ52. Wild-type swimming specifically reduced deposition on the upstream surfaces
of the micromodel collectors. Conducted under environmentally relevant
hydrodynamic conditions, the results suggest that swimming motility is an
important characteristic for bacterial deposition and transport in the
environment.
PMID- 26436255
TI - Pore-Scale Study of Flow Rate on Colloid Attachment and Remobilization in a
Saturated Micromodel.
AB - Colloid attachment is an important retention mechanism. It is influenced by
colloid size, pore size, and flow rate, among other factors. In this work, we
studied colloid attachment experimentally under various flow rates, as well as
colloid release in response to a rapid change of flow rate. Colloid transport
experiments under saturated conditions and with different flow rates were
conducted in a physical micromodel. The micromodel was made of
polydimethylsiloxane (PDMS), which is a hydrophobic polymer. Colloids were
hydrophilic fluorescent carboxylate-modified polystyrene latex microspheres with
a mean diameter of 300 nm. We could directly observe the movement of colloids
within the pores using a confocal microscope. We also obtained concentration
breakthrough curves by measuring the fluorescence intensity at the outlet of the
micromodel. In addition, our experiments were simulated using a pore-network
modeling, PoreFlow, based on the pore structure of the micromodel. Local colloid
concentrations were calculated by solving local mass balance equations for all
network elements and then averaging resulting concentrations over the whole
micromodel. The measured breakthrough curves were successfully simulated using
PoreFlow. Observed and calculated breakthrough curves showed that colloid
attachment rate was smaller for larger flow rate. Temporally enhance colloid
release (remobilization of attached colloids) was observed when the flow rate was
increased by a factor of 10. But no colloid remobilization was observed when the
flow rate decreased by a factor of 10.
PMID- 26436256
TI - Efficacy of Coral Sand for Removal of and Bacteriophage under Saturated Flow
Conditions.
AB - Knowledge of how effectively microbes are transported through porous media is
useful for water resource/wastewater management. Despite much research having
been done to characterize microbial contaminant transport through various
sedimentary materials, very little study has been made on coral sand, such as
constitutes the primary substrate of many Pacific atolls. We conducted a set of
laboratory column experiments as a preliminary examination of how effective coral
sand is at attenuating model pathogens J6-2 and MS2 bacteriophage (phage) under
saturated flow conditions mildly representative of field conditions at the
Bonriki freshwater lens, South Tarawa, Kiribati. The very poorly sorted gravelly
sand coral substrate tested proved very effective at attenuating the bacterial
tracer, and spatial removal rates of between 0.02 and 0.07 log cm were determined
for J6-2. The ability to determine precise removal rates for MS2 phage was
compromised by the use of a plastic apparatus, although the evidence weights
toward coral sand being less effective at attenuating MS2 phage than it is .
Further research is required to fully assess the ability of coral sand to remove
pathogens and to explore how this medium could be engineered into cost-effective
water/wastewater treatment solutions on Pacific atolls. The phage data from this
work highlight the limitations of using plastic apparatus in experiments targeted
at characterizing the fate and transport of viruses.
PMID- 26436257
TI - Attachment and Detachment Behavior of Human Adenovirus and Surrogates in Fine
Granular Limestone Aquifer Material.
AB - The transport of human adenovirus, nanoparticles, and PRD1 and MS2 bacteriophages
was tested in fine granular limestone aquifer material taken from a borehole at a
managed aquifer recharge site in Adelaide, South Australia. Comparison of
transport and removal of virus surrogates with the pathogenic virus is necessary
to understand the differences between the virus and surrogate. Because
experiments using pathogenic viruses cannot be done in the field, laboratory
tests using flow-through soil columns were used. Results show that PRD1 is the
most appropriate surrogate for adenovirus in an aquifer dominated by calcite
material but not under high ionic strength or high pH conditions. It was also
found that straining due to size and the charge of the colloid were not dominant
removal mechanisms in this system. Implications of this study indicate that a
certain surrogate may not represent a specific pathogen solely based on similar
size, morphology, and/or surface charge. Moreover, if a particular surrogate is
representative of a pathogen in one aquifer system, it may not be the most
appropriate surrogate in another porous media system. This was apparent in the
inferior performance of MS2 as a surrogate, which is commonly used in virus
transport studies.
PMID- 26436258
TI - Pathogen Decay during Managed Aquifer Recharge at Four Sites with Different
Geochemical Characteristics and Recharge Water Sources.
AB - Recycling of stormwater water and treated effluent via managed aquifer recharge
(MAR) has often been hampered because of perceptions of low microbiological
quality of recovered water and associated health risks. The goal of this study
was to assess the removal of selected pathogens in four large-scale MAR schemes
and to determine the influence of aquifer characteristics, geochemistry, and type
of recharge water on the pathogen survival times. Bacterial pathogens tested in
this study had the shortest one log removal time (, <3 d), followed by oocysts (,
<120 d), with enteric viruses having the biggest variability in removal times (,
18 to >200 d). Human adenovirus and rotavirus were relatively persistent under
anaerobic conditions (, >200 d). Human adenovirus survived longer than all the
other enteric virus tested in the study and hence could be used as a conservative
indicator for virus removal in groundwater during MAR. The results suggest that
site-specific subsurface conditions such as groundwater chemistry can have
considerable influence on the decay rates of enteric pathogens and that viruses
are likely to be the critical pathogens from a public health perspective.
PMID- 26436259
TI - Importance of the Colmation Layer in the Transport and Removal of Cyanobacteria,
Viruses, and Dissolved Organic Carbon during Natural Lake-Bank Filtration.
AB - This study focused on the importance of the colmation layer in the removal of
cyanobacteria, viruses, and dissolved organic carbon (DOC) during natural bank
filtration. Injection-and-recovery studies were performed at two shallow (0.5 m
deep), sandy, near-shore sites at the southern end of Ashumet Pond, a waste
impacted, kettle pond on Cape Cod, MA, that is subject to periodic blooms of
cyanobacteria and continuously recharges a sole-source drinking-water aquifer.
The experiment involved assessing the transport behaviors of bromide
(conservative tracer), sp. IU625 (cyanobacterium, 2.6 +/- 0.2 um), AS-1 (tailed
cyanophage, 110 nm long), MS2 (coliphage, 26 nm diameter), and carboxylate
modified microspheres (1.7 um diameter) introduced to the colmation layer using a
bag-and-barrel (Lee-type) seepage meter. The injectate constituents were tracked
as they were advected across the pond water-groundwater interface and through the
underlying aquifer sediments under natural-gradient conditions past push-point
samplers placed at ~30-cm intervals along a 1.2-m-long, diagonally downward flow
path. More than 99% of the microspheres, IU625, MS2, AS-1, and ~44% of the pond
DOC were removed in the colmation layer (upper 25 cm of poorly sorted bottom
sediments) at two test locations characterized by dissimilar seepage rates (1.7
vs. 0.26 m d). Retention profiles in recovered core material indicated that >82%
of the attached IU625 were in the top 3 cm of bottom sediments. The colmation
layer was also responsible for rapid changes in the character of the DOC and was
more effective (by three orders of magnitude) at removing microspheres than was
the underlying 20-cm-thick segment of sediment.
PMID- 26436260
TI - Transport of through a Thick Vadose Zone.
AB - Livestock manure applications on fields can be a source of contamination in water
resources, including groundwater. Although fecal indicators like have often been
detected in tile drainage systems, few studies have monitored groundwater at
depth after manure treatments, especially at sites with a deep, heterogeneous
vadose zone. Our hypothesis was that microbial transport through a thick vadose
zone would be limited or nonexistent due to attenuation processes, subsurface
thickness, and heterogeneity. This study tested this hypothesis by monitoring
concentrations beneath a 12-m-thick vadose zone of coarse, heterogeneous glacial
sediments after surface application of liquid swine manure. was detected on all
23 sample dates over the 5-mo period (4 Apr. 2012-13 Aug. 2012), with
particularly elevated concentrations 1 wk after application and lasting for 5 wk.
Variable low-level concentrations before and after the elevated period suggest
remobilization and delayed transport of microorganisms to the water table without
additional loadings within the flow field. These findings suggest preferential
flow pathways allowing deep infiltration of manure bacteria as well as a
continued source of bacteria, with variable retention and travel times, over
several months. Preferential flow pathways at this site include soil macropores,
depression focused infiltration, and pathways related to subsurface heterogeneity
and/or fracture flow through finer-grained diamict beds. Further research is
needed to confirm the relative contribution of sources, constrain travel times,
and define specific transport pathways.
PMID- 26436261
TI - Fecal Indicator and Pathogenic Bacteria and Their Antibiotic Resistance in
Alluvial Groundwater of an Irrigated Agricultural Region with Dairies.
AB - Surveys of microbiological groundwater quality were conducted in a region with
intensive animal agriculture in California, USA. The survey included monitoring
and domestic wells in eight concentrated animal feeding operations (CAFOs) and
200 small (domestic and community supply district) supply wells across the
region. was not detected in groundwater, whereas O157:H7 and were each detected
in 2 of 190 CAFO monitoring well samples. Nonpathogenic generic and spp. were
detected in 24.2% (46/190) and 97.4% (185/190) groundwater samples from CAFO
monitoring wells and in 4.2% (1/24) and 87.5% (21/24) of CAFO domestic wells,
respectively. Concentrations of both generic and spp. were significantly
associated with well depth, season, and the type of adjacent land use in the
CAFO. No pathogenic bacteria were detected in groundwater from 200 small supply
wells in the extended survey. However, 4.5 to 10.3% groundwater samples were
positive for generic and . Concentrations of generic were not significantly
associated with any factors, but concentrations of were significantly associated
with proximity to CAFOs, seasons, and concentrations of potassium in water. Among
a subset of and isolates from both surveys, the majority of (63.6%) and (86.1%)
isolates exhibited resistance to multiple (>=3) antibiotics. Findings confirm
significant microbial and antibiotic resistance loading to CAFO groundwater.
Results also demonstrate significant attenuative capacity of the unconfined
alluvial aquifer system with respect to microbial transport.
PMID- 26436262
TI - Characterizing Aquifer Heterogeneity Using Bacterial and Bacteriophage Tracers.
AB - Gravel aquifers act as important potable water sources in central western Europe,
yet they are subject to numerous contamination pressures. Compositional and
textural heterogeneity makes protection zone delineation around groundwater
supplies in these units challenging; artificial tracer testing aids
characterization. This paper reappraises previous tracer test results in light of
new geological and microbiological data. Comparative passive gradient testing,
using a fluorescent solute (Uranine), virus (H40/1 bacteriophage), and comparably
sized bacterial tracers and , was used to investigate a calcareous gravel
aquifer's ability to remove microbiological contaminants at a test site near
Munich, Germany. Test results revealed relative recoveries could exceed those of
H40/1 at monitoring wells, 10 m and 20 m from an injection well, by almost four
times; recoveries varied by a factor of up to three between wells. Application of
filtration theory suggested greater attenuation of H40/1 relative to similarly
charged occurred due to differences in microorganism size, while estimated
collision efficiencies appeared comparable. By contrast, more positively charged
experienced greater attenuation at one monitoring point, while lower attenuation
rates at the second location indicated the influence of geochemical
heterogeneity. Test findings proved consistent with observations from nearby
fresh outcrops that suggested thin open framework gravel beds dominated mass
transport in the aquifer, while discrete intervals containing stained clasts
reflect localized geochemical heterogeneity. Study results highlight the utility
of reconciling outcrop observations with artificial tracer test responses, using
microbiological tracers with well-defined properties, to characterize aquifer
heterogeneity.
PMID- 26436263
TI - Bacteria Transport in a Soil-Based Wastewater Treatment System under Simulated
Operational and Climate Change Conditions.
AB - Bacteria removal efficiencies in a conventional soil-based wastewater treatment
system (OWTS) have been modeled to elucidate the fate and transport of bacteria
under environmental and operational conditions that might be expected under
changing climatic conditions. The HYDRUS 2D/3D software was used to model the
impact of changing precipitation patterns, bacteria concentrations, hydraulic
loading rates (HLRs), and higher subsurface temperatures at different depths and
soil textures. Modeled effects of bacteria concentration shows that greater depth
of treatment was required in coarser soils than in fine-textured ones to remove .
The initial removal percentage was higher when HLR was lower, but it was greater
when HLR was higher. When a biomat layer was included in the transport model, the
performance of the system improved by up to 12.0%. Lower bacteria removal (<5%)
was observed at all depths under the influence of precipitation rates ranging
from 5 to 35 cm, and 35-cm rainfall combined with a 70% increase in HLR.
Increased subsurface temperature (23 degrees C) increased bacteria removal
relative to a lower temperature range (5-20 degrees C). Our results show that the
model is able to effectively simulate bacteria removal and the effect of
precipitation and temperature in different soil textures. It appears that the
performance of OWTS may be impacted by changing climate.
PMID- 26436264
TI - Langmuirian Blocking of Irreversible Colloid Retention: Analytical Solution,
Moments, and Setback Distance.
AB - Soil and aquifer materials have a finite capacity for colloid retention. Blocking
of the limited number of available retention sites further decreases the rate of
retention with time and enhances risks (e.g., pathogens or colloid-associated
contaminants) or benefits (e.g., remediation by microorganisms or nanoparticles)
of colloid migration. Our objective was to use a straightforward procedure, based
on variable transformation and Laplace transform, to solve the problem of
advective colloid transport with irreversible retention and Langmuirian blocking
for a pulse-type condition. Formulas for the mean breakthrough time and
retardation factor were obtained using zero- and first-order time moments of the
breakthrough curves. Equations for the time and position (setback distance) for a
particular colloid concentration were obtained from this information. D21 g
breakthrough curves and retention profiles in fine sand at four ionic strengths
were well described by the model when parameters were optimized. Illustrative
simulations demonstrated that blocking becomes more important for smaller
retention capacity () and for larger retention rate coefficient (), input
concentration (), and pulse duration. Blocking tended to delay colloid arrival
time at a particular location relative to a conservative tracer, and produced
larger setback distances for smaller and /.
PMID- 26436265
TI - Long-Term Impacts of Bacteria-Sediment Interactions in Watershed-Scale Microbial
Fate and Transport Modeling.
AB - Elevated levels of fecal indicator bacteria (FIB) remain the leading cause of
surface water-quality impairments in the United States. Under the Clean Water
Act, basin-specific total maximum daily load (TMDL) restoration plans are
responsible for bringing identified water impairments in compliance with
applicable standards. Watershed-scale model predictions of FIB concentrations
that facilitate the development of TMDLs are associated with considerable
uncertainty. An increasingly cited criticism of existing modeling practice is the
common strategy that assumes bacteria behave similarly to "free-phase"
contaminants, although many field evidence indicates a nontrivial number of cells
preferentially associate with particulates. Few attempts have been made to
evaluate the impacts of sediment on the predictions of in-stream FIB
concentrations at the watershed scale, with limited observational data available
for model development, calibration, and validation. This study evaluates the
impacts of bacteria-sediment interactions in a continuous, watershed-scale model
widely used in TMDL development. In addition to observed FIB concentrations in
the water column, streambed sediment-associated FIB concentrations were available
for model calibration. While improved model performance was achieved compared
with previous studies, model performance under a "sediment-attached" scenario was
essentially equivalent to the simpler "free-phase" scenario. Watershed-specific
characteristics (e.g., steep slope, high imperviousness) likely contributed to
the dominance of wet-weather pollutant loading in the water column, which may
have obscured sediment impacts. As adding a module accounting for bacteria
sediment interactions would increase the model complexity considerably, site
evaluation preceding modeling efforts is needed to determine whether the
additional model complexity and effort associated with partitioning phases of FIB
is sufficiently offset by gains in predictive capacity.
PMID- 26436267
TI - Implementing Effects-Based Water Quality Criteria for Eutrophication in Beaver
Lake, Arkansas: Linking Standard Development and Assessment Methodology.
AB - To address water quality standards needed to prevent accelerated eutrophication,
many states in the United States have developed effects-based standards related
to nutrients. In many cases, this has resulted in specific standards for Secchi
transparency (ST) and phytoplankton biomass measured as sestonic chlorophyll (chl
). The state of Arkansas recently adopted its first effects-based water quality
criteria for Beaver Lake in northwestern Arkansas, which was a growing-season
geometric mean chl- <8 MUg L and an annual average ST >1.1 m. However, the
adopted standard did not have a predefined assessment methodology that outlined
the frequency and duration of potential exceedances. This study used hydrologic
frequency analysis to estimate the risk of exceeding these water quality
standards using measured and modeled data from Beaver Lake from 2001 to 2014.
Beaver Lake conformed to common models in reservoir limnology in that ST was
least and chl- was greatest in the river-reservoir transition zone and decreased
in the downstream direction toward the dam. Greater chl- and lesser ST was
clearly related to total phosphorus concentrations along this gradient. Thus, the
risk of exceeding the water quality criteria decreased in a downstream direction.
There were substantial differences in the probability of exceeding the adopted
water quality criteria based on both spatial and temporal variation in the
potential assessment periods. Based on the way the standard was developed and the
risk of exceeding these standards derived from data collected before the
standards were in place, we recommend that a minimum of half of the years
assessed be necessary to result in a water quality violation. A number of other
assessment considerations are presented that could provide flexibility to
regulatory agencies in assessing water quality standards.
PMID- 26436268
TI - An Improved Indirect Procedure for Estimating Pesticide Volatility from Field
Trials.
AB - Conventional indirect approaches for estimating pesticide volatility from
agricultural fields require an air dispersion model and near-field, temporal air
concentration measurements. The model pesticide flux profile is chosen such that
field observations are recovered. Ross et al. (1996) first proposed a back
calculation method (BCM) using a single iteration of the Industrial Source
Complex Short Term (ISCST) parameterized by a unit source flux. The unit flux is
updated by scaling with the slope of a linear regression line between model
predictions and actual field observations at each measured time point and
location, yielding an estimate for the field flux that occurred over the sampling
period. The BCM is expanded using a downhill simplex optimization procedure
requiring many ISCST iterations to consecutively adjust the volatility flux rate
such that the sum of the squared residuals between predicted and measured air
concentrations is minimized (denoted as BCMO). The BCMO is ideally suited for
comparing the volatility of different pesticide formulations of the same active
from field studies performed simultaneously. Comparison of the BCM and BCMO from
field trials containing single (Texas) and multiple simultaneously treated fields
(Indiana) are provided for pesticides ranging from low to high volatility. The
advanced BCMO is a better alternative than the original BCM, as shown by closer
model predictions to measured air concentrations. A major advantage of the BCMO
is the ability to extract unique flux source strengths for each field when
multiple fields are present and treated consecutively and contiguously with each
field emitting pesticide mass at different rates.
PMID- 26436266
TI - QMRAcatch: Microbial Quality Simulation of Water Resources including Infection
Risk Assessment.
AB - Given the complex hydrologic dynamics of water catchments and conflicts between
nature protection and public water supply, models may help to understand
catchment dynamics and evaluate contamination scenarios and may support best
environmental practices and water safety management. A catchment model can be an
educative tool for investigating water quality and for communication between
parties with different interests in the catchment. This article introduces an
interactive computational tool, QMRAcatch, that was developed to simulate
concentrations in water resources of , a human-associated microbial source
tracking (MST) marker, enterovirus, norovirus, , and as target microorganisms and
viruses (TMVs). The model domain encompasses a main river with wastewater
discharges and a floodplain with a floodplain river. Diffuse agricultural sources
of TMVs that discharge into the main river are not included in this stage of
development. The floodplain river is fed by the main river and may flood the
plain. Discharged TMVs in the river are subject to dilution and temperature
dependent degradation. River travel times are calculated using the Manning
Gauckler-Strickler formula. Fecal deposits from wildlife, birds, and visitors in
the floodplain are resuspended in flood water, runoff to the floodplain river, or
infiltrate groundwater. Fecal indicator and MST marker data facilitate
calibration. Infection risks from exposure to the pathogenic TMVs by swimming or
drinking water consumption are calculated, and the required pathogen removal by
treatment to meet a health-based quality target can be determined. Applicability
of QMRAcatch is demonstrated by calibrating the tool for a study site at the
River Danube near Vienna, Austria, using field TMV data, including a sensitivity
analysis and evaluation of the model outcomes.
PMID- 26436269
TI - Impact of Storage Conditions on the Stability of Volatile Sulfur Compounds in
Sampling Bags.
AB - Odorous emissions from agricultural and waste management operations can cause
annoyance to local populations. Volatile sulfur compounds (VSCs) are dominant
odorants that are often lost during collection using sample bags. The degree of
VSC losses depends on factors such as storage time, bag materials, temperature,
sample relative humidity (RH), light exposure, and the presence of volatile
organic compounds (VOCs). To assess the impact of those factors on the stability
of 10 VSCs (hydrogen sulfide, methanethiol, ethanethiol, dimethyl sulfide, tert
butanethiol, ethyl methyl sulfide, 1-butanethiol, dimethyl disulfide, diethyl
disulfide, and dimethyl trisulfide), laboratory-based experiments were conducted
according to a factorial experimental design. Linear mixed-effects models were
constructed for loss predictions. The estimated recovery of HS in Tedlar bag was
8 to 10% higher than in Mylar and Nalophan between 6 and 30 h. At <=20 degrees C
and without being exposed to light, at least 75% relative recovery of the 10 VSCs
in Tedlar bags can be achieved after 18 h, whereas, a maximum of 12 h of storage
should not be exceeded to ensure a minimum of 74% relative recovery of the VSCs
in Mylar and Nalophan bags.
PMID- 26436270
TI - Effect of Alum Additions to Poultry Litter on In-House Ammonia and Greenhouse Gas
Concentrations and Emissions.
AB - Alum [Al(SO4) .14HO] addition to poultry litter has been shown to reduce ammonia
(NH) concentrations in poultry houses; however, its effects on greenhouse gas
(GHG; NO, CH, and CO) emissions is unknown. The objectives of this study were to
determine the effects of alum additions on (i) in-house NH and GHG
concentrations, (ii) NH and GHG emissions, and (iii) litter chemical properties.
Two identical broiler houses located in northwest Arkansas were used for this
study: one house was a control and the other was treated with alum between each
flock of birds. Ventilation rates were coupled with in-house NH and GHG
measurements to determine emission rates. Overall, alum additions significantly
reduced the daily average in-house NH concentration by 42% (8.9 vs. 15.4 MUL L),
and the overall NH emission rate was reduced by 47% (7.2 vs. 13.4 kg d house).
The average cumulative NH emission for the three flocks was 330 kg house flock
for the alum-treated house and 617 kg house flock for the control. Concentrations
and emissions of nitrous oxide (NO) and methane (CH) from the alum-treated house
were not significantly different than the untreated house. However, carbon
dioxide (CO) emissions were significantly higher from the untreated house than
the alum-treated house. Alum also significantly increased litter N content and
reduced the C/N ratio. These results indicate that the addition of alum to
poultry litter is not only an effective management practice for reducing in-house
NH concentrations and emissions but also significantly reduces CO emissions from
poultry facilities.
PMID- 26436271
TI - Biomass, Nutrient, and Trace Element Accumulation and Partitioning in Cattail (
L.) during Wetland Phytoremediation of Municipal Biosolids.
AB - Biomass and contaminant accumulation and partitioning in plants determine the
harvest stage for optimum contaminant uptake during phytoremediation of municipal
biosolids. This wetland microcosm bioassay characterized accumulation and
partitioning of biomass, nutrients (N and P), and trace elements (Zn, Cu, Cr, and
Cd) in cattail ( L.) in a growth room. Four cattail seedlings were transplanted
into each 20-L plastic pail containing 3.9 kg (dry wt.) biosolids from an end-of
life municipal lagoon. A 10-cm-deep water column was maintained above the 12-cm
thick biosolids layer. Plants were harvested every 14 d over a period of 126 d
for determination of aboveground biomass (AGB) and belowground biomass (BGB)
yields, along with contaminant concentrations in these plant tissues. Logistic
model fits to biomass yield data indicated no significant difference in
asymptotic yield between AGB and BGB. Aboveground biomass accumulated
significantly greater amounts of N and P and lower amounts of trace elements than
BGB. Maximum N accumulation in AGB occurred 83 d after transplanting (DAT), and
peak P uptake occurred at 86 DAT. Harvesting at maximum aboveground accumulation
removed (percent of the initial element concentration in the biosolids) 4% N, 3%
P, 0.05% Zn, 0.6% Cu, 0.1% Cd, and 0.2% Cr. Therefore, under the conditions of
this study, phytoremediation would be most effective if cattail is harvested at
86 DAT. These results contribute toward the identification of the harvest stage
that will optimize contaminant uptake and enhance in situ phytoremediation of
biosolids using cattail.
PMID- 26436272
TI - Detection of Purple Sulfur Bacteria in Purple and Non-purple Dairy Wastewaters.
AB - The presence of purple bacteria in manure storage lagoons is often associated
with reduced odors. In this study, our objectives were to determine the
occurrence of purple sulfur bacteria (PSB) in seven dairy wastewater lagoons and
to identify possible linkages between wastewater properties and purple blooms.
Community DNA was extracted from composited wastewater samples, and a
conservative 16S rRNA gene sequence within and genes found in both purple sulfur
and nonsulfur bacteria was amplified. Analysis of the genes indicated that all of
the lagoons contained sequences that were 92 to 97% similar with . Sequences from
a few lagoons were also found to be similar with other PSB, such as sp. (97%),
(93-100%), and (95-98%). sequences amplified from enrichment and pure cultures
were most similar to (93-96%). Carotenoid pigment concentrations, which were used
as an indirect measure of purple bacteria levels in the wastewaters, were found
to be positively correlated with salinity, nitrogen, total and volatile solids,
and chemical oxygen demand; however, salinity could be the dominant factor
influencing purple blooms. Due to the detection of PSB sequences in all lagoons,
our findings suggest that the non-purple lagoons may have been purple in the past
or may have the potential to become purple in the future.
PMID- 26436273
TI - Fecal Contamination in the Surface Waters of a Rural- and an Urban-Source
Watershed.
AB - Surface waters are commonly used as source water for drinking water and
irrigation. Knowledge of sources of fecal pollution in source watersheds benefits
the design of effective source water protection plans. This study analyzed the
relationships between enteric pathogens ( O157:H7, spp., and spp. [, and ]),
water quality (turbidity, temperature, and ), and human and ruminant-cow and
mitochondrial DNA (mtDNA)-based fecal source tracking (FST) markers in two source
watersheds. Water samples ( = 329) were collected at 10 sites (five in each
watershed) over 18 mo. The human marker (HF183) occurred in 9 to 10% of the water
samples at nine sampling sites; while a forested site in the urban watershed
tested negative. Ruminant-cow markers (BacR and CowM2) only appeared in the rural
watershed (6%). The mtDNA markers (HcytB and AcytB) showed the same pattern but
were less sensitive due to lower fecal concentrations. Higher prevalences ( <
0.05) of spp. (41 vs. 16% for the rural and urban watershed, respectively) and
O157:H7 (12 vs. 3%) were observed in the rural watershed, while spp. levels were
comparable (23-28%). Densities of >=100 colony-forming units (CFU) 100 mL
increased the odds ( < 0.05) of detecting the enteric bacterial pathogens. The
water turbidity levels (nephelometric turbidity units [NTU] >= 1.0) similarly
predicted ( < 0.05) pathogen presence. Storm events increased ( < 0.01) pathogen
and fecal marker concentrations in the waterways. The employment of multiple FST
methods suggested failing onsite wastewater systems contribute to human fecal
pollution in both watersheds.
PMID- 26436274
TI - Evaluation of AGRO-2014 for Predicting Hydrophobic Organic Chemical
Concentrations in Ponds.
AB - Highly hydrophobic organic chemicals (HOCs), like pyrethroids, adsorb strongly to
eroded soil and suspended sediment. Therefore, total suspended solids (TSS)
concentration in the water column of receiving waters is important for
determining the proportion of chemical in the sediment-sorbed vs. the dissolved
(bioavailable) state. However, most current regulatory exposure models, such as
the Exposure Analysis Modeling System (EXAMS) and Variable Volume Water Model
(VVWM), do not include dynamic modeling of TSS. The objective of this study is to
compare the performance of those models for simulating observed pesticide
concentrations in small water bodies with an updated version of the AGRO model,
called AGRO-2014, which includes dynamic sediment processes. The paper also
evaluates the importance of explicitly modeling sediment dynamics for HOCs. We
calibrated AGRO-2014 for small, static, water bodies using published pyrethroid
mesocosm data. To improve the basis for intermodel comparison, AGRO-2014 includes
the same algorithm for temperature-dependent degradation found in EXAMS and VVWM,
direct acceptance of organic C partition coefficient () inputs, and acceptance of
user-defined pesticide loading durations. Differences in sediment processes in
AGRO-2014, EXAMS, and VVWM significantly affected predicted concentrations of
high- compounds for standardized loading scenarios, whereas differences between
the models were less evident for compounds with lower sorption to sediments. AGRO
2014 simulations of drift and slurry pyrethroid applications to ponds closely
matched observed concentrations, while EXAMS and VVWM simulations underestimated
the observations. The publicly available AGRO-2014 model offers improvements over
other models for predicting concentrations of HOC compounds in small water
bodies.
PMID- 26436275
TI - Benefits of the Use of Sewage Sludge over EDTA to Remediate Soils Polluted with
Heavy Metals.
AB - Sewage sludges from urban wastewater treatment plants are often used to remediate
degraded soils. However, the benefits of their use in metal-polluted soils remain
unclear and need to be assessed in terms of factors besides soil fertility. This
study examines the use of thermal-dried sewage sludge (TDS) as an amendment for
heavy metal-polluted soil in terms of its effects on soil chemical properties,
leachate composition, and the growth of native plant communities. To assess the
response of the soil and its plant community to an increase in metal
mobilization, the effects of TDS amendment were compared with those of the
addition of a chelating agent (ethylenediaminetetraacetic acid [EDTA]). The
experimental design was based on a real-case scenario in which soils from of an
abandoned mine site were used in a greenhouse bioassay. Two doses of TDS and EDTA
were applied to a soil containing high Pb, Zn, Cu, and Cd levels (4925, 5675,
404, and 25 mg kg, respectively). Soil pH was 6.4, and its organic matter content
was 5.53%. The factors examined after soil amendment were soil fertility and
heavy metal contents, leachate element losses, the plant community arising from
the seed bank (plant cover, species richness and biodiversity, above/below ground
biomass), and phytotoxic effects (chemical contents of abundant species). Thermal
dried sewage sludge emerged as a good phytostabilizer of Pb, Zn, Cu, and Cd given
its capacity to reduce the plant uptake of metals and achieve rapid plant cover.
This amendment also enhanced the retention of other elements in the plant root
system and overall showed a better capacity to remediate soils polluted with
several heavy metals. The addition of EDTA led to plant productivity losses and
nutritional imbalances because it increased the mobility of several elements in
the soil and its leachates.
PMID- 26436276
TI - Long-Term Observations of Nitrogen and Phosphorus Export in Paired-Agricultural
Watersheds under Controlled and Conventional Tile Drainage.
AB - Controlled tile drainage (CTD) regulates water and nutrient export from tile
drainage systems. Observations of the effects of CTD imposed en masse at
watershed scales are needed to determine the effect on downstream receptors. A
paired-watershed approach was used to evaluate the effect of field-to-field CTD
at the watershed scale on fluxes and flow-weighted mean concentrations (FWMCs) of
N and P during multiple growing seasons. One watershed (467-ha catchment area)
was under CTD management (treatment [CTD] watershed); the other (250-ha catchment
area) had freely draining or uncontrolled tile drainage (UCTD) (reference [UCTD]
watershed). The paired agricultural watersheds are located in eastern Ontario,
Canada. Analysis of covariance and paired tests were used to assess daily fluxes
and FWMCs during a calibration period when CTD intervention on the treatment
watershed was minimal (2005-2006, when only 4-10% of the tile-drained area was
under CTD) and a treatment period when the treatment (CTD) watershed had prolific
CTD intervention (2007-2011 when 82% of tile drained fields were controlled,
occupying >70% of catchment area). Significant linear regression slope changes
assessed using ANCOVA ( <= 0.1) for daily fluxes from upstream and downstream
monitoring sites pooled by calibration and treatment period were -0.06 and -0.20
(stream water) (negative values represent flux declines in CTD watershed), -0.59
and -0.77 (NH-N), -0.14 and -0.15 (NO-N), -1.77 and -2.10 (dissolved reactive P),
and -0.28 and 0.45 (total P). Total P results for one site comparison contrasted
with other findings likely due to unknown in-stream processes affecting total P
loading, not efficacy of CTD. The FWMC results were mixed and inconclusive but
suggest physical abatement by CTD is the means by which nutrient fluxes are
predominantly reduced at these scales. Overall, our study results indicate that
CTD is an effective practice for reducing watershed scale fluxes of stream water,
N, and P during the growing season.
PMID- 26436277
TI - Selecting Color-based Tracers and Classifying Sediment Sources in the Assessment
of Sediment Dynamics Using Sediment Source Fingerprinting.
AB - The use of sediment color as a fingerprint property to determine sediment sources
is an emerging technique that can provide a rapid and inexpensive means of
investigating sediment sources. The present study aims to test the feasibility of
color fingerprint properties to apportion sediment sources within the South
Tobacco Creek Watershed (74 km) in Manitoba, Canada. Suspended sediment from 2009
to 2011 at six monitoring stations and potential source samples along the main
stem of the creek were collected. Reflectance spectra of sediments and source
materials were quantified using a diffuse reflectance spectrometry, and 16 color
coefficients were derived from several color space models. Canonical discriminant
analysis was used to reclassify and downsize sediment source groups. After the
linear additive test and stepwise discriminant function analysis, four color
coefficients were chosen to fit the Stable Isotope Analysis in R model.
Consistent with the conventional fingerprinting approach, the color fingerprint
results demonstrated a switch in the dominant sediment source between the
headwaters and the outlet of the watershed, with the main sources being topsoil
in the upper reaches, whereas outcrop shale and stream bank materials dominated
in the lower reaches. The color fingerprinting approach can be integrated with
conventional fingerprints (e.g., geochemical and fallout radionuclide properties)
to improve source discrimination, which is a key component for source ascription
modeling. We concluded that the use of color fingerprints is a promising, cost
effective technique for sediment source fingerprinting.
PMID- 26436278
TI - A Methodological Approach for Spatiotemporally Analyzing Water-Polluting
Effluents in Agricultural Landscapes Using Partial Triadic Analysis.
AB - Multivariate techniques for two-dimensional data matrices are normally used in
water quality studies. However, if the temporal dimension is included in the
analysis, other statistical techniques are recommended. In this study, partial
triadic analysis was used to investigate the spatial and temporal variability in
water quality variables sampled in a northeastern Spain river basin. The results
highlight the spatiality of the physical and chemical properties of water at
different sites along a river over 1 yr. Partial triadic analysis allowed us to
clearly identify the presence of a stable spatial structure that was common to
all sampling dates across the entire catchment. Variables such as electrical
conductivity and Na and Cl ions were associated with agricultural sources,
whereas total dissolved nitrogen, NH-N concentrations, and NO-N concentrations
were linked to polluted urban sites; differences were observed between irrigated
and nonirrigated periods. The concentration of NO-N was associated with both
agricultural and urban land uses. Variables associated with urban and
agricultural pollution sources were highly influenced by the seasonality of
different activities conducted in the study area. In analyzing the impact of land
use and fertilization management on water runoff and effluents, powerful
statistical tools that can properly identify the causes of pollution in
watersheds are important. Partial triadic analysis can efficiently summarize site
specific water chemistry patterns in an applied setting for land- and water
monitoring schemes at the landscape level. The method is recommended for land-use
decision-making processes to reduce harmful environmental effects and promote
sustainable watershed management.
PMID- 26436279
TI - Degradation of Herbicide Mesotrione in Three Soils with Differing Physicochemical
Properties from China.
AB - The movement and fate of herbicides in soils under various environmental factors
are important in evaluating their mobility and ecological impact. The effects of
sterilization, solarization, and soil physicochemical properties on the
degradation of herbicide mesotrione in three soils from China were evaluated
using laboratory incubation method, and the degradation kinetics were also
simulated using pseudo first-order reaction model. The calculated half-lives ()
of mesotrione were found to be 3.78- to 5.24-fold increased in sterilized soils
than nonsterilized soils, which indicated that the degradation of mesotrione was
strongly affected by soil microbial activity. A certain role of promoting
degradation effect of natural light was found, and the values appeared to be only
7.90, 15.89, and 25.29 d in the surface of paddy soil, sandy loess, and silt clay
loam, respectively. Correlation analysis between the observed first-order
reaction rate constant () values and the selected soil properties revealed that
the degradation of mesotrione was highly dependent on soil pH value ( > 0.992)
and organic matter content ( > 0.932), but less related with clay content (<0.02
mm) with < 0.761 and nonrelated with cation exchange capacity (CEC) ( < 0.164).
Data obtained in this study are helpful for further research on the prediction of
the movement and fate of mesotrione in soils in limiting its environmental
impact.
PMID- 26436280
TI - Subsurface Drainage Nitrate and Total Reactive Phosphorus Losses in Bioenergy
Based Prairies and Corn Systems.
AB - We compare subsurface-drainage NO-N and total reactive phosphorus (TRP)
concentrations and yields of select bioenergy cropping systems and their
rotational phases. Cropping systems evaluated were grain-harvested corn-soybean
rotations, grain- and stover-harvested continuous corn systems with and without a
cover crop, and annually harvested reconstructed prairies with and without the
addition of N fertilizer in an Iowa field. Drainage was monitored when soils were
unfrozen during 2010 through 2013. The corn-soybean rotations without residue
removal and continuous corn with residue removal produced similar mean annual
flow-weighted NO-N concentrations, ranging from 6 to 18.5 mg N L during the 4-yr
study. In contrast, continuous corn with residue removal and with a cover crop
had significantly lower NO-N concentrations of 5.6 mg N L when mean annual flow
weighted values were averaged across the 4 yr. Prairies systems with or without N
fertilization produced significantly lower concentrations below <1 mg NO-N L than
all the row crop systems throughout the study. Mean annual flow-weighted TRP
concentrations and annual yields were generally low, with values <0.04 mg TRP L
and <0.14 kg TRP ha, and were not significantly affected by any cropping systems
or their rotational phases. Bioenergy-based prairies with or without N
fertilization and continuous corn with stover removal and a cover crop have the
potential to supply bioenergy feedstocks while minimizing NO-N losses to drainage
waters. However, subsurface drainage TRP concentrations and yields in bioenergy
systems will need further evaluation in areas prone to higher levels of P losses.
PMID- 26436281
TI - Characterizing the Performance of Denitrifying Bioreactors during Simulated
Subsurface Drainage Events.
AB - The need to mitigate nitrate export from corn and soybean fields with subsurface
(tile) drainage systems, a major environmental issue in the midwestern United
States, has made the efficacy of field-edge, subsurface bioreactors an active
subject of research. This study of three such bioreactors located on the
University of Illinois South Farms during their first 6 mo of operation (July
Dec. 2012) focused on the interactions of seasonal temperature changes and
hydraulic retention times (HRTs), which were subject to experimental
manipulation. Changes in nitrate, phosphate, oxygen, and dissolved organic carbon
were monitored in influent and effluent to assess the benefits and the potential
harmful effects of bioreactors for nearby aquatic ecosystems. On average,
bioreactors reduced nitrate loads by 63%, with minimum and maximum reductions of
20 and 98% at low and high HRTs, respectively. The removal rate per unit reactor
volume averaged 11.6 g NO-N m d (range, 5-30 g NO-N m d). Multiple regression
models with exponential dependencies on influent water temperature and on HRT
explained 73% of the variance in NO-N load reduction and 43% of the variance in
its removal rate. Although concentrations of dissolved reactive phosphorus and
dissolved organic carbon in the bioreactor effluent increased relative to the
influent by an order of magnitude during initial tests, within 1 mo of operation
they stabilized at nearly equal values.
PMID- 26436282
TI - Alum and Rainfall Effects on Ionophores in Runoff from Surface-Applied Broiler
Litter.
AB - Polyether ionophores, monensin, and salinomycin are commonly used as
antiparasitic drugs in broiler production and may be present in broiler litter
(bird excreta plus bedding material). Long-term application of broiler litter to
pastures may lead to ionophore contamination of surface waters. Because polyether
ionophores break down at low pH, we hypothesized that decreasing litter pH with
an acidic material such as aluminum sulfate (alum) would reduce ionophore losses
to runoff (i.e., monensin and salinomycin concentrations, loads, or amounts
lost). We quantified ionophore loss to runoff in response to (i) addition of alum
to broiler litter and (ii) length of time between litter application and the
first simulated rainfall event. The factorial experiment consisted of unamended
(~pH 9) vs. alum-amended litters (~pH 6), each combined with simulated rainfall
at 0, 2, or 4 wk after litter application. Runoff from alum-amended broiler
litter had 33% lower monensin concentration ( < 0.01), 57% lower monensin load (
< 0.01), 48% lower salinomycin concentration ( < 0.01), and 66% lower salinomycin
load ( < 0.01) than runoff from unamended broiler litter when averaged across all
events of rainfall. Ionophore losses to runoff were also less when rainfall was
delayed for 2 or 4 wk after litter application relative to applying rainfall
immediately after litter application. While the weather is difficult to predict,
our data suggest that ionophore losses in runoff can be reduced if broiler litter
applications are made to maximize dry time after application.
PMID- 26436283
TI - Leaching of Glyphosate and Aminomethylphosphonic Acid through Silty Clay Soil
Columns under Outdoor Conditions.
AB - Glyphosate [-(phosphono-methyl)-glycine] is the main herbicide used in the
Chianti vineyards. Considering the pollution risk of the water table and that the
vineyard tile drain may deliver this pollutant into nearby streams, the objective
of the present study was to estimate the leaching losses of glyphosate under
natural rainfall conditions in a silty clay soil in the Chianti area. The
leaching of glyphosate and its metabolite (aminomethylphosphonic acid [AMPA])
through soils was studied in 1-m-deep soil columns under outdoor conditions over
a 3-yr period. Glyphosate was detected in the leachates for up to 26 d after
treatments at concentrations ranging between 0.5 and 13.5 MUg L. The final peak
(0.28 MUg L) appeared in the leachates approximately 319 d after the first annual
treatment. Aminomethylphosphonic acid first appeared (21.3 MUg L) in the soil
leachate 6.8 d after the first annual treatment. Aminomethylphosphonic acid
detection frequency and measured concentration in the leachates were more than
that observed for the glyphosate. Aminomethylphosphonic acid was detected in 20%
of the soil leachates at concentrations ranging from 1 to 24.9 MUg L. No
extractable glyphosate was detected in the soil profile. However, the AMPA
content in the lowest layer ranged from 13.4 to 21.1 mg kg, and on the surface
layer, it ranged from 86.7 to 94 mg kg. Overall, these results indicate that both
glyphosate and AMPA leaching through a 1-m soil column may be potential
groundwater contaminants.
PMID- 26436284
TI - Use of Zeolite with Alum and Polyaluminum Chloride Amendments to Mitigate Runoff
Losses of Phosphorus, Nitrogen, and Suspended Solids from Agricultural Wastes
Applied to Grassed Soils.
AB - Diffuse pollutant losses containing phosphorus (P), nitrogen (N), and suspended
solids (SS) can occur when agricultural wastes are applied to soil. This study
aimed to mitigate P, N, and SS losses in runoff from grassed soils, onto which
three types of agricultural wastes (dairy slurry, pig slurry, and dairy-soiled
water [DSW]), were applied by combining amendments of either zeolite and
polyaluminum chloride (PAC) with dairy and pig slurries or zeolite and alum with
DSW. Four treatments were investigated in rainfall simulation studies: (i)
control soil, (ii) agricultural wastes, (iii) dairy and pig slurries amended with
PAC and DSW amended with alum, and (iv) dairy and pig slurries amended with
zeolite and PAC and DSW amended with zeolite and alum. Our data showed that
combined amendments of zeolite and PAC applied to dairy and pig slurries reduced
total P (TP) in runoff by 87 and 81%, respectively, compared with unamended
slurries. A combined amendment of zeolite and alum applied to DSW reduced TP in
runoff by 50% compared with unamended DSW. The corresponding reductions in total
N (TN) were 56% for dairy slurry and 45% for both pig slurry and DSW. Use of
combined amendments reduced SS in runoff by 73 and 44% for dairy and pig slurries
and 25% for DSW compared with unamended controls, but these results were not
significantly different from those using chemical amendments only. The findings
of this study are that combined amendments of zeolite and either PAC or alum
reduce TP and TN losses in runoff to a greater extent than the use of single PAC
or alum amendments and are most effective when used with dairy slurry and pig
slurry but less effective when used with DSW.
PMID- 26436285
TI - Beaver Ponds: Resurgent Nitrogen Sinks for Rural Watersheds in the Northeastern
United States.
AB - Beaver-created ponds and dams, on the rise in the northeastern United States,
reshape headwater stream networks from extensive, free-flowing reaches to
complexes of ponds, wetlands, and connecting streams. We examined seasonal and
annual rates of nitrate transformations in three beaver ponds in Rhode Island
under enriched nitrate-nitrogen (N) conditions through the use of N mass balance
techniques on soil core mesocosm incubations. We recovered approximately 93% of
the nitrate N from our mesocosm incubations. Of the added nitrate N, 22 to 39%
was transformed during the course of the incubation. Denitrification had the
highest rates of transformation (97-236 mg N m d), followed by assimilation into
the organic soil N pool (41-93 mg N m d) and ammonium generation (11-14 mg N m
d). Our denitrification rates exceeded those in several studies of freshwater
ponds and wetlands; however, rates in those ecosystems may have been limited by
low concentrations of nitrate. Assuming a density of 0.7 beaver ponds km of
catchment area, we estimated that in nitrate-enriched watersheds, beaver pond
denitrification can remove approximately 50 to 450 kg nitrate N km catchment
area. In rural watersheds of southern New England with high N loading (i.e., 1000
kg km), denitrification from beaver ponds may remove 5 to 45% of watershed
nitrate N loading. Beaver ponds represent a relatively new and substantial sink
for watershed N if current beaver populations persist.
PMID- 26436286
TI - Prevalence of and Relationship between Two Human-Associated DNA Biomarkers for
Bacteroidales in an Urban Watershed.
AB - Human-associated fecal biomarkers offer potent tools for the detection and
control of human fecal pollution in watersheds. In some cases, the probability of
false-negative findings may call for using a less specific biomarker that is
present in higher quantities as long as it can be related to the more specific
indicator. The objective of this study is to investigate the relationship between
two previously published human-associated biomarkers for Bacteroidales bacteria
in an urban watershed influenced by human fecal pollution and to determine if the
less specific marker may be used to identify the locations of broken or leaking
sewer lines. Samples were collected from 19 stream locations on 10 dates. Sample
DNA was extracted and qPCR analysis was conducted for the HuBac and qHF183
biomarkers. The HuBac biomarker was detected more frequently than the qHF183
biomarker and in greater quantities when both were detected. A strong linear
relationship ( = 0.91) between the two markers was observed in 219 samples taken
from both the watershed and inlet sewage. The relationship between the two
biomarkers showed less variance at higher concentrations. However, even when the
inlet sewage samples were excluded from the dataset, a clear linear relationship
remained ( = 0.74). The results indicate that use of a less specific, but more
sensitive, biomarker may provide greater utility when the prevention of false
negatives is necessary and the primary fecal source is known, as in spatial
distribution studies of human fecal pollution in an urban watershed.
PMID- 26436288
TI - Prototype Sodium-Ion Batteries Using an Air-Stable and Co/Ni-Free O3-Layered
Metal Oxide Cathode.
AB - A prototype rechargeable sodium-ion battery using an O3-Na0.90[Cu0.22 Fe0.30
Mn0.48]O2 cathode and a hard carbon anode is demonstrated to show an energy
density of 210 W h kg(-1) , a round-trip energy efficiency of 90%, a high rate
capability (up to 6C rate), and excellent cycling stability.
PMID- 26436287
TI - Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms
in Mice.
AB - Osmotic pumps continuously deliver compounds at a constant rate into small
animals. This article introduces a standard protocol used to induce aortic
aneurysms via subcutaneous infusion of angiotensin II (AngII) from implanted
osmotic pumps. This protocol includes calculation of AngII amount and
dissolution, osmotic pump filling, implantation of osmotic pumps subcutaneously,
observation after pump implantation, and harvest of aortas to visualize aortic
aneurysms in mice. Subcutaneous infusion of AngII through osmotic pumps following
this protocol is a reliable and reproducible technique to induce both abdominal
and thoracic aortic aneurysms in mice. Infusion durations range from a few days
to several months based on the purpose of the study. AngII 1,000 ng/kg/min is
sufficient to provide maximal effects on abdominal aortic aneurysmal formation in
male hypercholesterolemic mouse models such as apolipoprotein E deficient or low
density lipoprotein receptor deficient mice. Incidence of abdominal aortic
aneurysms induced by AngII infusion via osmotic pumps is 5-10 times lower in
female hypercholesterolemic mice and also lower in both genders of
normocholesterolemic mice. In contrast, AngII-induced thoracic aortic aneurysms
in mice are not hypercholesterolemia or gender-dependent. Importantly, multiple
features of this mouse model recapitulate those of human aortic aneurysms.
PMID- 26436289
TI - Enhancement in the excitonic spontaneous emission rates for Si nanocrystal multi
layers covered with thin films of Au, Ag, and Al.
AB - The enhancement in the spontaneous emission rate (SER) for Ag, Au, and Al films
on multilayer Si nanocrystals (SiNCs) was probed with time-resolved
cathodoluminescence (CL). The SiNCs were grown on Si(100) using plasma enhanced
chemical vapor deposition. Electron-hole pairs were generated in the metal
covered SiNCs by injecting a pulsed high-energy electron beam through the thin
metal films, which is found to be an ideal method of excitation for plasmonic
quantum heterostructures and nanostructures that are opaque to laser or light
excitation. Spatially, spectrally, and temporally resolved CL was used to measure
the excitonic lifetime of the SiNCs in metal-covered and bare regions of the same
samples. The observed enhancement in the SER for the metal-covered SiNCs,
relative to the SER for the bare sample, is attributed to a coupling of the SiNC
excitons with surface plasmon polaritons (SPPs) of the thin metal films. A
maximum SER enhancement of ~2.0, 1.4 and 1.2 was observed for the Ag, Au, and Al
films, respectively, at a temperature of 55 K. The three chosen plasmonic metals
of Ag, Au, and Al facilitate an interesting comparison of the exciton-SPP
coupling for metal films that exhibit varying differences between the surface
plasmon energy, omega(sp), and the SiNC excitonic emission energy. A modeling of
the temperature dependence of the Purcell enhancement factor, Fp, was performed
and included the temperature dependence of the dielectric properties of the
metals.
PMID- 26436290
TI - Impact of visceral metastases on outcome to abiraterone after docetaxel in
castration-resistant prostate cancer patients.
AB - BACKGROUND: The objective of this study was to analyze the impact of visceral
metastases in castration-resistant prostate cancer (CRPC) treated with
abiraterone. MATERIALS & METHODS: All CRPC patients received abiraterone 1000 mg
daily plus prednisone 10 mg orally daily. Liver and lung metastases were
considered as visceral metastases. RESULTS: Of 265 CRPC patients, 49 had visceral
metastases. Results on progression-free survival were not significantly different
in patients with or without visceral metastases. Conversely, the median overall
survival between the two groups was 12.4 and 18.5 months (p = 0.01),
respectively, and median overall survival of patients with liver-only disease
versus other sites was 10.5 versus 18.5 months (p = 0.006), respectively.
CONCLUSION: Visceral disease appears to be an important predictor of clinical
outcome in CRPC patients treated with abiraterone.
PMID- 26436291
TI - beta-Blocker-Associated Risks in Patients With Uncomplicated Hypertension
Undergoing Noncardiac Surgery.
AB - IMPORTANCE: Perioperative beta-blocker strategies are important to reduce risks
of adverse events. Effectiveness and safety may differ according to patients'
baseline risk. OBJECTIVE: To determine the risk of major adverse cardiovascular
events (MACEs) associated with long-term beta-blocker therapy in patients with
uncomplicated hypertension undergoing noncardiac surgery. DESIGN, SETTING, AND
PARTICIPANTS: Association study based on in-hospital records and out-of-hospital
pharmacotherapy use using a Danish nationwide cohort of patients with
uncomplicated hypertension treated with at least 2 antihypertensive drugs (beta
blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS]
inhibitors) undergoing noncardiac surgery between 2005 and 2011. INTERVENTIONS:
Various antihypertensive treatment regimens, chosen as part of usual care. MAIN
OUTCOMES AND MEASURES: Thirty-day risk of MACEs (cardiovascular death, nonfatal
ischemic stroke, nonfatal myocardial infarction) and all-cause mortality,
assessed using multivariable logistic regression models and adjusted numbers
needed to harm (NNH). RESULTS: The baseline characteristics of the 14,644
patients who received beta-blockers (65% female, mean [SD] age, 66.1 [12.0]
years) were similar to those of the 40,676 patients who received other
antihypertensive drugs (57% female, mean [SD] age, 65.9 [11.8] years). Thirty-day
MACEs occurred in 1.3% of patients treated with beta-blockers compared with 0.8%
of patients not treated with beta-blockers (P < .001). beta-Blocker use was
associated with increased risks of MACEs in 2-drug combinations with RAS
inhibitors (odds ratio [OR], 2.16 [95% CI, 1.54-3.04]), calcium antagonists (OR,
2.17 [95% CI, 1.48-3.17]), and thiazides (OR, 1.56 [95% CI, 1.10-2.22]), compared
with the reference combination of RAS inhibitors and thiazides. Results were
similar for all-cause mortality. Risk of MACEs associated with beta-blocker use
seemed especially pronounced for patients at least 70 years old (number needed to
harm [NNH], 140 [95% CI, 86-364]), for men (NNH, 142 [95% CI, 93-195]), and for
patients undergoing acute surgery (NNH, 97 [95% CI, 57-331]), compared with
patients younger than 70 years, women, and patients undergoing elective surgery,
respectively. CONCLUSIONS AND RELEVANCE: Antihypertensive treatment with a beta
blocker may be associated with increased risks of perioperative MACEs and all
cause mortality in patients with uncomplicated hypertension.
PMID- 26436292
TI - Multiphase Oscillatory Flow Strategy for in Situ Measurement and Screening of
Partition Coefficients.
AB - Taking advantage of the difference between the surface energies of aqueous and
organic solvents on a Teflon substrate, a fully automated small-scale strategy is
developed on the basis of gas-driven oscillatory motion of a biphasic slug for
high-throughput in situ measurement and screening of partition coefficients of
organic substances between aqueous and organic phases. The developed oscillatory
flow strategy enables single partition coefficient data point measurement within
8 min (including the sample preparation time) which is 360 times faster than the
conventional "shake-flask" method, while using less than a 30 MUL volume of the
two phases and 9 nmol of the target organic substance. The developed multiphase
strategy is validated using a conventional shake-flask technique. Finally, the
developed strategy is extended to include automated screening of partition
coefficients at physiological temperature.
PMID- 26436294
TI - A conversation for the holidays: part II "what matters to you".
PMID- 26436293
TI - Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron
dependent HERC2-mediated proteolysis.
AB - NCOA4 is a selective cargo receptor for the autophagic turnover of ferritin, a
process critical for regulation of intracellular iron bioavailability. However,
how ferritinophagy flux is controlled and the roles of NCOA4 in iron-dependent
processes are poorly understood. Through analysis of the NCOA4-FTH1 interaction,
we demonstrate that direct association via a key surface arginine in FTH1 and a C
terminal element in NCOA4 is required for delivery of ferritin to the lysosome
via autophagosomes. Moreover, NCOA4 abundance is under dual control via autophagy
and the ubiquitin proteasome system. Ubiquitin-dependent NCOA4 turnover is
promoted by excess iron and involves an iron-dependent interaction between NCOA4
and the HERC2 ubiquitin ligase. In zebrafish and cultured cells, NCOA4 plays an
essential role in erythroid differentiation. This work reveals the molecular
nature of the NCOA4-ferritin complex and explains how intracellular iron levels
modulate NCOA4-mediated ferritinophagy in cells and in an iron-dependent
physiological setting.
PMID- 26436295
TI - Overcoming resistance to family-witnessed resuscitation.
AB - Giving family members the option of being present during resuscitation has been
shown to be beneficial for both family and staff. However, only a small
percentage of intensive care units have policies promoting family-witnessed
resuscitation. This article reviews current research showing the benefits of
family-witnessed resuscitation, outlines how to successfully integrate a family
facilitator during resuscitation, and includes research that has been effective
in changing the prevailing attitudes of staff. The authors also argue for the
resuscitation team to practice ethical and cultural humility when involving
family members so that all resuscitation efforts are a success, whether the
patient lives or dies.
PMID- 26436296
TI - Pronation therapy case report: nurse's perspective and lessons learned.
AB - This article describes a brief review of prone therapy and its efficacy and
effect on mortality in the treatment of acute respiratory distress syndrome.
Furthermore, the situational background and clinical events that transpired prior
to, during, and after the institution of pronation therapy for Elkhart General
Hospital's Critical Care Center's first pronation patient using the RotoProne
Therapy System are described from the nurse's perspective. The lessons learned
from this first experience have led to the formation of several practice-based
recommendations for future patient care.
PMID- 26436297
TI - Facilitating palliative care referrals in the intensive care unit: a pilot
project.
AB - BACKGROUND: Palliative care in intensive care units (ICUs) reduces costs and
improves outcomes yet is consistently underused; studies suggest that screening
tools increase the use of palliative services. AIMS: This project piloted the use
of the Palliative Performance Scale, version 2 (PPSv2), as a trigger for
palliative care referrals in a 12-bed medical ICU. METHODS: Using a
preintervention-postintervention design, the authors measured the effect of the
intervention on nurses' comfort and knowledge in assessing palliative care needs,
number of palliative care referrals, and number of days between ICU admission and
palliative care referral. The authors also measured uptake of the scale over 12
weeks of implementation and asked nurses to share their thoughts about using the
PPSv2. RESULTS: Over 610 observations, the rate of uptake increased over time and
use of the scale ranged from 24.2% to 85.6%. The nurses' (n = 26) comfort with
palliative care issues increased from preintervention to postintervention, albeit
not significantly. Knowledge items did not change. There was a 110% increase in
the number of palliative care referrals between preintervention and
postintervention and a nearly 1-day decrease in the number of days between
medical ICU admission and palliative care referral; this reduction was not
statistically significant. A majority of nurses (n = 22 [84.5%]) voted to retain
the PPSv2 as an official process of care, stating that the tool facilitated
assessment of patient needs that might have been previously overlooked.
CONCLUSION: Data suggest that the PPSv2 was well received by the bedside nurses
and changed practice patterns with regard to facilitating palliative care
services.
PMID- 26436299
TI - Care of the patient with pulmonary arterial hypertension.
AB - Patients presenting with pulmonary arterial hypertension (PAH), the rarest of the
groups of pulmonary hypertension diagnoses, are infrequently seen in the critical
care arena. However, when patients with PAH present in the intensive care unit,
it is generally related to an exhaustion of treatments. This article focuses on
the current state of the literature addressing the group designation,
pathophysiology, symptom expression, and treatment modalities of the patient with
PAH.
PMID- 26436301
TI - Promotion of progressive mobility activities with ventricular assist and
extracorporeal membrane oxygenation devices in a cardiothoracic intensive care
unit.
AB - BACKGROUND: Progressive mobility (PM) is a clinical intervention that influences
complications experienced throughout critical illness. Early PM is a relevant
topic in critical care practice literature and was principle to introducing a PM
care guideline in an acute cardiothoracic/cardiovascular intensive care unit.
PURPOSE: A noted challenge in the cardiothoracic/cardiovascular intensive care
unit is caring for acute cardiac and pulmonary failure. Often, these patients
require prolonged mechanical circulatory support via extracorporeal mechanical
oxygenation or a ventricular assist device. This article describes safe and
effective progressive mobilization for patients experiencing MCS in a case study
format. This article also highlights how a multidisciplinary clinical team
supports mobility practice in specific critical care roles. CONCLUSIONS: Post
intensive care syndrome is composed of various health implications that occur
following critical illness. Recent data suggest improved care outcomes when
critically ill patients are awake and participate in active physical
rehabilitation as early as clinically possible. The case studies presented
indicate that mobility, to the point of ambulation, is a feasible clinical
expectation when patients present with substantial acute respiratory and cardiac
failure and are managed with MCS. CLINICAL IMPLICATIONS: Development of a PM
guideline uses a critical appraisal of practice evidence, highlights
multidisciplinary collaboration, and increases progression to ambulation.
Mobility for complex patients is attainable, as demonstrated in the postguideline
outcomes. The PM guideline provides structure to primary caregivers and promotes
safe practices. The PM guideline facilitates an advanced level of care, promotes
safe practices, champions holistic recovery, and encourages active patient
involvement, goals satisfying to both patients and staff.
PMID- 26436302
TI - Qualitative research: the "what," "why," "who," and "how"!
AB - There has been a general view of qualitative research as a lower level form of
inquiry and the diverse conceptualizations of what it is, its use or utility, its
users, the process of how it is conducted, and its scientific merit. This
fragmented understanding and varied ways in which qualitative research is
conceived, synthesized, and presented have a myriad of implications in
demonstrating and enhancing the utilization of its findings and the ways and
skills required in transforming knowledge gained from it. The purpose of this
article is to define qualitative research and discuss its significance in
research, the questions it addresses, its characteristics, methods and criteria
for rigor, and the type of results it can offer. A framework for understanding
the "what," "why," "who," and "how" of qualitative research; the different
approaches; and the strategies to achieve trustworthiness are presented.
Qualitative research provides insights into health-related phenomena and seeks to
understand and interpret subjective experience and thus humanizes health care and
can enrich further research inquiries and be made clearer and more rigorous as it
is relevant to the perspective and goals of nursing.
PMID- 26436303
TI - Letter to the editor, re: better pain management for elders in the intensive care
unit.
PMID- 26436304
TI - Authors' response.
PMID- 26436305
TI - The INANE experience.
PMID- 26436306
TI - Prevalence and risk factors of coronary artery disease in patients with chronic
viral hepatitis.
AB - OBJECTIVES: Patients with chronic viral hepatitis usually present metabolic
abnormalities and hemodynamic changes, which are known factors associated with
the development of coronary artery disease (CAD). This study aims to determine
the risk factors of incident CAD in these patients. METHODS: We identified 193
patients who subsequently developed CAD amongst 37,840 cases diagnosed as chronic
viral hepatitis from January 2007 through December 2013. RESULTS: In these
patients, 141 had hepatitis B virus infections and 52 had hepatitis C virus
infections. There was a male preponderance (65.9%). The median age at the
diagnosis of hepatitis was 51 years. In the univariate analysis, patients aged >=
51 years had shorter median periods from the diagnosis of hepatitis to the onset
of CAD than patients aged < 51 years (50 versus 96 months, p < 0.001), and
patients with hypertension had shorter median durations compared to those without
hypertension (48 versus 96 months, p < 0.001). Statistical significance also
existed between patients with different etiologies (p = 0.004). In the
multivariate analysis by Cox regression, age at the diagnosis of hepatitis (p <
0.001; hazard ratio (HR), 1.041; 95% CI, 1.027-1.056) and hypertension (with
versus without, p < 0.001; HR, 1.925; 95% CI, 1.419-2.611) were revealed.
CONCLUSIONS: Age at diagnosis of hepatitis and hypertension appeared to be
independent risk factors of incident CAD in these patients. This topic deserves
further studies.
PMID- 26436307
TI - Mercury speciation and selenium in toothed-whale muscles.
AB - Mercury accumulates at high levels in marine mammal tissues. However, its
speciation is poorly understood. The main goal of this investigation was to
establish the relationships among mercury species and selenium (Se)
concentrations in toothed-whale muscles at different mercury levels. The
concentrations of total mercury (T-Hg), methylmercury (MeHg), inorganic mercury
(I-Hg) and Se were determined in the muscles of four toothed-whale species:
bottlenose dolphins (n=31), Risso's dolphins (n=30), striped dolphins (n=29), and
short-finned pilot whales (n=30). In each species, the MeHg concentration
increased with increasing T-Hg concentration, tending to reach a plateau. In
contrast, the proportion of MeHg in T-Hg decreased from 90-100% to 20-40%. The
levels of T-Hg and Se showed strong positive correlations. Se/I-Hg molar ratios
rapidly decreased with the increase of I-Hg and reached almost 1 in all species.
These results suggested that the demethylated MeHg immediately formed Se/I-Hg
equimolar complex of mercury selenide (HgSe) in their muscles. In addition, an X
ray absorption fine structure analysis (XAFS) of a bottlenose dolphin muscle
confirmed that the dominant chemical form of the Se/I-Hg equimolar complex was
HgSe. HgSe was mainly localized in cells near the endomysium using electron probe
microanalysis (EPMA). These results suggested that the demethylated MeHg finally
deposits within muscle cells of bottlenose dolphin as an inert HgSe.
PMID- 26436309
TI - The cytochrome c oxidase biogenesis factor AtCOX17 modulates stress responses in
Arabidopsis.
AB - COX17 is a soluble protein from the mitochondrial intermembrane space that
participates in the transfer of copper for cytochrome c oxidase (COX) assembly in
eukaryotic organisms. In this work, we studied the function of both Arabidopsis
thaliana AtCOX17 genes using plants with altered expression levels of these
genes. Silencing of AtCOX17-1 in a cox17-2 knockout background generates plants
with smaller rosettes and decreased expression of genes involved in the response
of plants to different stress conditions, including several genes that are
induced by mitochondrial dysfunctions. Silencing of either of the AtCOX17 genes
does not affect plant development or COX activity but causes a decrease in the
response of genes to salt stress. In addition, these plants contain higher
reactive oxygen and lipid peroxidation levels after irrigation with high NaCl
concentrations and are less sensitive to abscisic acid. In agreement with a role
of AtCOX17 in stress and abscisic acid responses, both AtCOX17 genes are induced
by several stress conditions, abscisic acid and mutation of the transcription
factor ABI4. The results indicate that AtCOX17 is required for optimal expression
of a group of stress-responsive genes, probably as a component of signalling
pathways that link stress conditions to gene expression responses.
PMID- 26436310
TI - Conceptual and methodological issues in research on mindfulness and meditation.
AB - Both basic science and clinical research on mindfulness, meditation, and related
constructs have dramatically increased in recent years. However, interpretation
of these research results has been challenging. The present article addresses
unique conceptual and methodological problems posed by research in this area.
Included among the key topics is the role of first-person experience and how it
can be best studied, the challenges posed by intervention research designs in
which true double-blinding is not possible, the nature of control and comparison
conditions for research that includes mindfulness or other meditation-based
interventions, issues in the adequate description of mindfulness and related
trainings and interventions, the question of how mindfulness can be measured,
questions regarding what can and cannot be inferred from self-report measures,
and considerations regarding the structure of study design and data analyses.
Most of these topics are germane to both basic and clinical research studies and
have important bearing on the future scientific understanding of mindfulness and
meditation.
PMID- 26436312
TI - When mindfulness is therapy: Ethical qualms, historical perspectives.
AB - In the past 20 years, mindfulness therapeutic programs have moved firmly into the
mainstream of clinical practice and beyond. As they have, we have also seen the
development of an increasingly vocal critique. At issue is often less whether or
not these mindfulness practices "work," and more whether there is a danger in
dissociating them from the ethical frameworks for which they were originally
developed. Mindfulness, the argument goes, was never supposed to be about weight
loss, better sex, helping children perform better in school, helping employees be
more productive in the workplace, or even improving the functioning of anxious,
depressed people. It was never supposed to be a merchandized commodity to be
bought and sold. The larger clinical and religious community, however, has not
always been troubled by the idea that (PsycINFO Database Record
PMID- 26436314
TI - Beyond the confines of culture: Reflections of two non-American psychologists.
AB - Comments on the original article by Christopher et al. (see record 2014-20055
001) regarding "culturally situated" psychology. In this commentary, the current
authors articulate a few points of contention and words of caution to be borne in
mind when attempting to cultivate critical cultural awareness.
PMID- 26436315
TI - Revisiting cultural awareness and cultural relevancy.
AB - Comments on the original article by Christopher et al. (see record 2014-20055
001) regarding critical cultural awareness. The more insights and exploration of
the meaning and influence of culture we receive, the better. There is no single
treatment of any personal or collective culture(s) that can be inherently
complete or totally exhaustive. New hermeneutics and skills are always needed,
appreciated, and refreshing.
PMID- 26436311
TI - Prospects for a clinical science of mindfulness-based intervention.
AB - Mindfulness-based interventions (MBIs) are at a pivotal point in their future
development. Spurred on by an ever-increasing number of studies and breadth of
clinical application, the value of such approaches may appear self-evident. We
contend, however, that the public health impact of MBIs can be enhanced
significantly by situating this work in a broader framework of clinical
psychological science. Utilizing the National Institutes of Health stage model
(Onken, Carroll, Shoham, Cuthbert, & Riddle, 2014), we map the evidence base for
mindfulness-based cognitive therapy and mindfulness-based stress reduction as
exemplars of MBIs. From this perspective, we suggest that important gaps in the
current evidence base become apparent and, furthermore, that generating more of
the same types of studies without addressing such gaps will limit the relevance
and reach of these interventions. We offer a set of 7 recommendations that
promote an integrated approach to core research questions, enhanced
methodological quality of individual studies, and increased logical links among
stages of clinical translation in order to increase the potential of MBIs to
impact positively the mental health needs of individuals and communities.
PMID- 26436313
TI - Investigating the phenomenological matrix of mindfulness-related practices from a
neurocognitive perspective.
AB - There has been a great increase in literature concerned with the effects of a
variety of mental training regimes that generally fall within what might be
called contemplative practices, and a majority of these studies have focused on
mindfulness. Mindfulness meditation practices can be conceptualized as a set of
attention-based, regulatory, and self-inquiry training regimes cultivated for
various ends, including wellbeing and psychological health. This article examines
the construct of mindfulness in psychological research and reviews recent,
nonclinical work in this area. Instead of proposing a single definition of
mindfulness, we interpret it as a continuum of practices involving states and
processes that can be mapped into a multidimensional phenomenological matrix
which itself can be expressed in a neurocognitive framework. This
phenomenological matrix of mindfulness is presented as a heuristic to guide
formulation of next-generation research hypotheses from both cognitive/behavioral
and neuroscientific perspectives. In relation to this framework, we review
selected findings on mindfulness cultivated through practices in traditional and
research settings, and we conclude by identifying significant gaps in the
literature and outline new directions for research.
PMID- 26436316
TI - Cultural humility: The cornerstone of positive contact with culturally different
individuals and groups?
AB - Comments on the original article by Christopher et al. (see record 2014-20055
001) regarding cultural and folk psychologies. As noted by Christopher, Wendt,
Marecek, and Goodman (2014), "U.S. psychology remains not only overwhelmingly
U.S.- centric but also largely unaware of how its cultural roots shape theory and
research.
PMID- 26436317
TI - Culture revisited: A reply to comments.
AB - Replies to comments by Winston & Maher (see record 2015-45553-005), Abi-Hashem
(see record 2015-45553-006), and Hook & Watkins (see record 2015-45553-007), on
the original article by Christopher et al. (see record 2014-20055-001). In this
brief response, the authors clarify some elements of their thinking and address
some misconceptions put forward by the commentators.
PMID- 26436318
TI - The gender similarities hypothesis is untestable as formulated.
AB - Comments on the original article by Zell et al. (see record 2015-00137-002)
regarding gender similarities and differences using a metasynthesis approach. The
authors concluded that the average difference between males and females across
psychological domains is relatively small (d = 0.21), with the majority of
effects being either small or very small, thereby supporting Hyde's (2005) gender
similarities hypothesis that males and females are similar on most psychological
dimensions. Unfortunately, their study suffers from the same flaw as nearly all
studies testing that hypothesis, namely that it does not provide a metric for
either the psychological importance or relevance of the dimensions considered nor
does it supply an individuation rule for counting dimensions.
PMID- 26436319
TI - Global gender differences can be operationalized and tested.
AB - Replies to comments by Zuriff (see record 2015-45553-009) on the original article
by Zell et al. (see record 2015-00137-002). The authors appreciate the commentary
on their report by Zuriff (2015, this issue) and welcome the opportunity to
discuss several important issues that he raises.
PMID- 26436320
TI - Validity and completeness of colorectal cancer diagnoses in a primary care
database in the United Kingdom.
AB - PURPOSE: To validate the recorded diagnoses of colorectal cancer (CRC) and
identify false negatives in The Health Improvement Network (THIN) primary care
database. METHODS: We conducted a validation study of incident CRC cases in THIN
among patients aged 40-89 years from 2000-2011. CRC Read code entries (N = 3805)
were verified by manual review of patients' electronic medical records (EMRs)
including free-text comments. Incident CRC cases in THIN ascertained following
manual review were validated against two data sources deemed gold standards: (i)
questionnaires sent to primary care practitioners (PCPs; for a random sample of
100 potential CRC cases), and (ii) Hospital Episode Statistics (HES) among linked
practices. False negatives in THIN were identified by searching for International
Classification of Diseases-10 codes related to CRC in HES. RESULTS: Of 3805 CRC
cases identified in THIN via Read codes, 3033 patients (80.0%) were considered
definite cases after manual review of EMRs. The positive predictive value (PPV)
of CRC Read codes was 86.0% after removing patients identified from THIN via a
Read code for 'fast track referral for suspected CRC'. The response rate from
PCPs was 87.0% (n = 87), and the PPV of CRC in THIN was 100% based on PCP
questionnaires. Using HES, the PPV for CRC in THIN was 97.9% (556/568), and false
negative rate was 6.1% (36/592). CONCLUSIONS: CRC diagnostic Read codes in THIN
have a high PPV, which is increased further following manual review of free-text
comments. The false negative rate of CRC diagnoses in THIN is low.
PMID- 26436321
TI - Adherence to airway clearance therapy in pediatric cystic fibrosis: Socioeconomic
factors and respiratory outcomes.
AB - OBJECTIVES: The evidence linking socioeconomic status (SES) and adherence in
cystic fibrosis (CF) is inconclusive and focused on medication uptake. We
examined associations between SES, adherence to airway clearance therapy (ACT),
and CF respiratory outcomes. STUDY DESIGN: Socioeconomic, clinical, and adherence
data of CF patients (N = 110) at a single CF Center were evaluated in this cross
sectional observational study. SES was operationalized as maternal and paternal
education and household income. Adherence to ACT was measured with utilization
data from the high-frequency chest wall oscillation (HFCWO) device over 4-6
weeks. Statistical modeling was used to test three hypotheses: (H1) Higher SES is
associated with higher ACT adherence; (H2) Higher SES is associated with better
respiratory outcomes; and (H3) ACT adherence mediates the relationship between
SES and respiratory outcomes. RESULTS: In multinomial logistic regression,
maternal college education, annual income >$50,000, and more adults in the
household were independently related to better adherence (P < 0.05). Paternal
college education, income >$100,000, and lack of exposure to smoking were
independently related to higher lung function (P < 0.05). Current adherence to
ACT with HFCWO was not associated with lung function over 12 months. CONCLUSIONS:
SES is associated both with ACT adherence and respiratory outcomes in pediatric
CF patients. However, the link between SES and respiratory outcomes in this study
was not mediated by adherence to ACT with HFCWO. These data emphasize the
importance of socioeconomic resources and household environment for CF health.
Family socio-demographic profiles can help identify patients at increased risk
for ACT nonadherence.
PMID- 26436322
TI - Internalized Homonegativity: A Systematic Mapping Review of Empirical Research.
AB - Internalized homonegativity (IH) is an important variable affecting the wellbeing
of lesbian, gay, and bisexual (LGB) persons. We included 201 studies in a
systematic mapping review of IH. Most studies were conducted in North America and
examined IH as a predictor of poor health. The primary focus of 14 studies was IH
scale measurement, and, in total, these studies detailed nine distinct scales.
Eighteen studies compared levels of IH in LGB populations, four described
prevention programs, and one investigated IH using qualitative methods. Our
review indicates that further research is needed, particularly qualitative
research and ways to ameliorate IH.
PMID- 26436323
TI - Pancreas After Islet Transplantation: A First Report of the International
Pancreas Transplant Registry.
AB - Pancreas after islet (PAI) transplantation is a treatment option for patients
seeking insulin independence through a whole-organ transplant after a failed
cellular transplant. This report from the International Pancreas Transplant
Registry (IPTR) and the United Network for Organ Sharing (UNOS) studied PAI
transplant outcomes over a 10-year time period. Forty recipients of a failed
alloislet transplant subsequently underwent pancreas transplant alone (50%),
pancreas after previous kidney transplant (22.5%), or simultaneous pancreas and
kidney (SPK) transplant (27.5%). Graft and patient survival rates were not
statistically significantly different compared with matched primary pancreas
transplants. Regardless of the recipient category, overall 1- and 5-year PAI
patient survival rates for all 40 cases were 97% and 83%, respectively; graft
survival rates were 84% and 65%, respectively. A failed previous islet transplant
had no negative impact on kidney graft survival in the SPK category: It was the
same as for primary SPK transplants. According to this IPTR/UNOS analysis, a PAI
transplant is a safe procedure with low recipient mortality, high graft-function
rates in both the short and long term and excellent kidney graft outcomes.
Patients with a failed islet transplant should know about this alternative in
their quest for insulin independence through transplantation.
PMID- 26436324
TI - Thermodynamic Analysis of the Two-Liquid Model for Anomalies of Water, HDL-LDL
Fluctuations, and Liquid-Liquid Transition.
AB - After reviewing the protocol-dependent properties of HDA, which thermally anneals
to LDA, and the data gap over an unusually large T-range between HDA, LDA, and
water, we investigate whether or not, despite HDA's ill-defined state and
distinction from a glass, the HDL-LDL fluctuations view of the two-liquid model
can explain water's anomalous behavior. An analysis of the density, rho,
compressibility, beta, heat capacity, Cp, and thermal conductivity, kappa, of
water over a monotonic (continuous) path bridging this data gap shows the
following: (i) Such a path between rhowater at 320 K and rhoHDA yields an
untenable thermal expansion coefficient of water. (ii) There is neither a
continuous path between betawater at 353 K and betaHDA, nor between Cp,water at
363 K and Cp,HDA. (iii) The same value of rhowater, of betawater, or of Cp,water
at two temperatures separated by a maxima or a minima is incompatible with the
HDL-LDL fluctuations view. (iv) kappaLDA at ~140 K is about twice that of kappa
water at 253 K. (v) kappaHDA at 120 K is incompatible with kappawater at T > 320
K. Thus, there is an internal inconsistency between the thermodynamics of HDA
seen as a glass and that of water seen as an HDL-LDL mixture, which is
incompatible with both the HDL-LDL fluctuations view and the liquid-liquid
transition.
PMID- 26436325
TI - A sensitive and label-free photoelectrochemical aptasensor using Co-doped ZnO
diluted magnetic semiconductor nanoparticles.
AB - Co-doped ZnO diluted magnetic semiconductor as a novel photoelectric beacon was
first constructed for photoelectrochemical (PEC) aptasensor of acetamiprid. The
fabricated PEC sensing is based on the specific binding of acetamiprid and its
aptamer, which induces the decreasement of enhanced photocurrent produced by the
electron donor of quercetin. Co(2+) doping has a beneficial effect in extending
the band width of light absorption of ZnO into the visible region and to promote
the separation of the photoinduced carriers due to the sp-d exchange interactions
existing between the band electrons and the localized d electrons of Co(2+). The
fabricated aptasensor was linear with the concentration of acetamiprid in the
range of 0.5-800 nmolL(-1) with the detection limit of 0.18 nmolL(-1). The
presence of same concentration of other conventional pesticides did not interfere
in the detection of acetamiprid and the recovery is between 96.2% and 103.7%.
This novel PEC aptasensor has good performances with high sensitivity, good
selectivity, low cost and portable features. The strategy of Co-doped ZnO diluted
magnetic semiconductor paves a new way to improve the performances of PEC
aptasensor.
PMID- 26436326
TI - Real-time concentration monitoring in microfluidic system via plasmonic
nanocrescent arrays.
AB - In this work, on-chip bio/chemical sensor was reported based on localized surface
plasmon resonance of nanocrescent patterns fabricated via electron beam
lithography. The nanocrescent arrays with different dimensional features
exhibited controllable plasmonic properties in accordance with the simulation
results based on the finite-difference time-domain model. The highest refractive
index sensitivity of the fabricated samples was achieved to be ~699.2 nm/RIU with
a figure of merit of ~3.1 when the two opposite crescents own a gap of ~43.3 nm.
Such obtained plasmonic sensor was further integrated into the microfluidic
system which can simply control the specific analyte concentrations via tuning
the flow rate ratios between two injecting microstreams. Our method has
successfully demonstrated the capability of the nanocrescent patterns as on-chip
plasmonic bio/chemical sensor for real-time monitoring of dynamic concentrations
in the microchannel.
PMID- 26436327
TI - Biomimetic sensor based on molecularly imprinted polymer with nitroreductase-like
activity for metronidazole detection.
AB - The utility of molecularly imprinted polymer (MIP) as electrochemical sensor
often suffers from its limited catalytic efficiency. Here, we proposed an
alternative approach by combining the concept of MIP with the use of mimetic
enzyme. A metronidazole imprinted polymer with nitroreductase-like activity was
successfully achieved via an electrochemical method, where melamine served two
purposes: functional monomer of MIP and component of mimetic enzyme. During the
imprinting process, the redox-active center, which is responsible for catalysis,
was introduced into the imprinted cavities. Accordingly, the imprinted polymer,
having both catalysis centers and recognition sites, exhibited enhanced
electrocatalytic activity and selectivity. The sensing performances of this
metronidazole imprinted biomimetic sensor were evaluated in detail. Results
revealed that the response to metronidazole was linear in the concentration range
of 0.5-1000 MUM, and the detection limit was 0.12 MUM (S/N=3). In addition, we
applied the proposed sensor to detect metronidazole in an injection solution and
the results implied its feasibility for practical application.
PMID- 26436328
TI - A novel diagnostic biosensor for distinguishing immunoglobulin mutated and
unmutated types of chronic lymphocytic leukemia.
AB - In chronic lymphocytic leukemia (CLL), the immunoglobulin heavy-chain variable
(IgVH) region may be mutated (Ig-mutated CLL) or unmutated (Ig-unmutated CLL);
and the presence or absence of mutations in this region of CLL cells
distinguishes two clinically distinct forms. It is important for physicians to
distinguish between patients with Ig-unmutated CLL, where typically have more
indolent disease with median survivals close to 25 years, and Ig-mutated CLL,
where have more aggressive disease with median survivals around eight years. In
this work, a biosensor capable of diagnosis and distinguishing between these two
types of CLL was reported. The biosensor was fabricated by modifying a gold
electrode with gold nanoparticles (AuNPS) followed by coating of ZAP70
oligonucleotide probe on the surface to detect specific sequence of ZAP70 gene.
ZAP70 could predict the IgVH mutation status and is a good marker for
differentiating Ig-mutated and Ig-unmutated CLL and serve as prognostic marker.
First, we focused on achieving hybridization between probe and its complementary
sequence. Hybridization between probe and target was determined with
electrochemical impedance spectroscopy (EIS). Then, our efforts turned to
optimize the conditions for the detection of any point mutation and also to
maximize the selectivity. Under optimal conditions, the biosensor has a good
calibration range between 2.0 * 10(-14) and 1.0 * 10(-9)molL(-1), with ZAP70 DNA
sequence detection limit of 4.0 * 10(-15)molL(-1). We successfully detect
hybridization first in synthetic samples, and ultimately in blood samples from
patients. Experimental results illustrated that the nanostructured biosensor
clearly discriminates between mutated and non-mutated CLL and predict the IgVH
mutation status, which it has been considered as the single most informative
stage independent prognostic factor in CLL.
PMID- 26436329
TI - Dasatinib-induced nephrotic syndrome.
PMID- 26436330
TI - Dimethylfumarate Impairs Neutrophil Functions.
AB - Host defense against pathogens relies on neutrophil activation. Inadequate
neutrophil activation is often associated with chronic inflammatory diseases.
Neutrophils also constitute a significant portion of infiltrating cells in
chronic inflammatory diseases; eg psoriasis and multiple sclerosis. Fumarates
improve the latter diseases, which so far has been attributed to effects on
lymphocytes and dendritic cells. Here, we focused on effects of dimethyl fumarate
(DMF) on neutrophils. In vitro, DMF inhibited neutrophil activation, including
changes in surface marker expression, reactive oxygen species production,
formation of neutrophil extracellular traps and migration. Phagocytic ability and
autoantibody-induced, neutrophil-dependent tissue injury ex vivo was also
impaired by DMF. Regarding the mode of action, DMF modulates -in a stimulus
dependent manner- neutrophil activation using the PI3K/Akt-p38 MAPK- and ERK 1/2
pathways. For in vivo validation, mouse models of epidermolysis bullosa acquisita
(EBA), an organ-specific autoimmune disease caused by autoantibodies to type VII
collagen (COL7), were employed. In the presence of DMF, blistering induced by
injection of anti-COL7 antibodies into mice was significantly impaired. DMF
treatment of mice with clinically already manifested EBA led to disease
improvement. Collectively, we demonstrate a profound inhibitory activity of DMF
on neutrophil functions. These findings encourage wider use of DMF in patients
with neutrophil-mediated diseases.Journal of Investigative Dermatology accepted
article preview online, 05 October 2015. doi:10.1038/jid.2015.361.
PMID- 26436331
TI - Perampanel in the treatment of focal and idiopathic generalized epilepsies and of
status epilepticus.
AB - Perampanel is the latest approved antiepileptic drug in focal and generalized
epilepsies and has a distinct and selective mode of action on AMPA-receptors.
Several thousand patients have received perampanel within randomized placebo
controlled trials, open-label extension trials and post-marketing observational
studies. Significant median partial-onset seizure reduction rates of 23% for 4
mg/day, 26-31% for 8 mg/day and 18-35% for 12 mg/day were reported. Likewise 50
percent responder rates were 29% for 4 mg/day, 33-38% for 8 mg/day and 34-36% for
12 mg/day. Primary generalized tonic-clonic seizures were reduced by 76.5% (8 mg)
vs 38.4% (placebo) in a recent controlled trial. Overall, perampanel is well
tolerated and the main adverse events are dizziness, somnolence and fatigue.
There are also anecdotal reports on use in progressive myoclonic epilepsies and
status epilepticus. Perampanel will likely remain an important, possibly broad
spectrum AED with a significant market share, especially in patients with drug
refractory epilepsies.
PMID- 26436333
TI - Gender-responsiveness in corrections: Estimating female inmate misconduct risk
using the Personality Assessment Inventory (PAI).
AB - Proper inmate assessment is critical to correctional management and institutional
security. While many instruments have been developed to assist with this process,
most of these tools have not been validated using samples of female inmates
although distinct gender differences have been identified in the inmate
population in terms of adaptation and misconduct. The Personality Assessment
Inventory (PAI) is a multiscale measure of psychopathology that is being
increasingly utilized in the correctional setting to assist with the inmate
classification process. The current study contributes to the dearth of literature
surrounding gender-responsive inmate classification by utilizing a sample of
2,000 female inmates to examine the incremental and predictive validity of the
PAI in association with general and assaultive disciplinary infractions. Findings
from this study reveal that the PAI scales presenting the strongest relationship
to general and assaultive disciplinary infractions among this female sample
included Aggression (AGG), Antisocial Features (ANT), Paranoia (PAR), and the
Violence Potential Index (VPI). Moreover, findings derived from this study
suggest that certain PAI measures, specifically ARD-T, DRU, and more general
substance abuse and mental health indicators may be useful in gender-responsive
assessments during the female inmate classification process.
PMID- 26436332
TI - Visualization of miniSOG Tagged DNA Repair Proteins in Combination with Electron
Spectroscopic Imaging (ESI).
AB - The limits to optical resolution and the challenge of identifying specific
protein populations in transmission electron microscopy have been obstacles in
cell biology. Many phenomena cannot be explained by in vitro analysis in
simplified systems and need additional structural information in situ,
particularly in the range between 1 nm and 0.1 um, in order to be fully
understood. Here, electron spectroscopic imaging, a transmission electron
microscopy technique that allows simultaneous mapping of the distribution of
proteins and nucleic acids, and an expression tag, miniSOG, are combined to study
the structure and organization of DNA double-strand break repair foci.
PMID- 26436334
TI - Holistic face processing can inhibit recognition of forensic facial composites.
AB - Facial composite systems help eyewitnesses to show the appearance of criminals.
However, likenesses created by unfamiliar witnesses will not be completely
accurate, and people familiar with the target can find them difficult to
identify. Faces are processed holistically; we explore whether this impairs
identification of inaccurate composite images and whether recognition can be
improved. In Experiment 1 (n = 64) an imaging technique was used to make
composites of celebrity faces more accurate and identification was contrasted
with the original composite images. Corrected composites were better recognized,
confirming that errors in production of the likenesses impair identification. The
influence of holistic face processing was explored by misaligning the top and
bottom parts of the composites (cf. Young, Hellawell, & Hay, 1987). Misalignment
impaired recognition of corrected composites but identification of the original,
inaccurate composites significantly improved. This effect was replicated with
facial composites of noncelebrities in Experiment 2 (n = 57). We conclude that,
like real faces, facial composites are processed holistically: recognition is
impaired because unlike real faces, composites contain inaccuracies and holistic
face processing makes it difficult to perceive identifiable features. This effect
was consistent across composites of celebrities and composites of people who are
personally familiar. Our findings suggest that identification of forensic facial
composites can be enhanced by presenting composites in a misaligned format.
PMID- 26436335
TI - Memory and the operational witness: Police officer recall of firearms encounters
as a function of active response role.
AB - Investigations after critical events often depend on accurate and detailed recall
accounts from operational witnesses (e.g., law enforcement officers, military
personnel, and emergency responders). However, the challenging, and often
stressful, nature of such events, together with the cognitive demands imposed on
operational witnesses as a function of their active role, may impair subsequent
recall. We compared the recall performance of operational active witnesses with
that of nonoperational observer witnesses for a challenging simulated scenario
involving an armed perpetrator. Seventy-six police officers participated in
pairs. In each pair, 1 officer (active witness) was armed and instructed to
respond to the scenario as they would in an operational setting, while the other
(observer witness) was instructed to simply observe the scenario. All officers
then completed free reports and responded to closed questions. Active witnesses
showed a pattern of heart rate activity consistent with an increased stress
response during the event, and subsequently reported significantly fewer correct
details about the critical phase of the scenario. The level of stress experienced
during the scenario mediated the effect of officer role on memory performance.
Across the sample, almost one-fifth of officers reported that the perpetrator had
pointed a weapon at them although the weapon had remained in the waistband of the
perpetrator's trousers throughout the critical phase of the encounter. These
findings highlight the need for investigator awareness of both the impact of
operational involvement and stress-related effects on memory for ostensibly
salient details, and reflect the importance of careful and ethical information
elicitation techniques.
PMID- 26436336
TI - Surface Acidity as Descriptor of Catalytic Activity for Oxygen Evolution Reaction
in Li-O2 Battery.
AB - Unraveling the descriptor of catalytic activity, which is related to physical
properties of catalysts, is a major objective of catalysis research. In the
present study, the first-principles calculations based on interfacial model were
performed to study the oxygen evolution reaction mechanism of Li2O2 supported on
active surfaces of transition-metal compounds (TMC: oxides, carbides, and
nitrides). Our studies indicate that the O2 evolution and Li(+) desorption
energies show linear and volcano relationships with surface acidity of catalysts,
respectively. Therefore, the charging voltage and desorption energies of Li(+)
and O2 over TMC could correlate with their corresponding surface acidity. It is
found that certain materials with an appropriate surface acidity can achieve the
high catalytic activity in reducing charging voltage and activation barrier of
rate-determinant step. According to this correlation, CoO should have as active
catalysis as Co3O4 in reducing charging overpotential, which is further confirmed
by our comparative experimental studies. Co3O4, Mo2C, TiC, and TiN are predicted
to have a relatively high catalytic activity, which is consistent with the
previous experiments. The present study enables the rational design of catalysts
with greater activity for charging reactions of Li-O2 battery.
PMID- 26436337
TI - Assessing personal financial management in patients with bipolar disorder and its
relation to impulsivity and response inhibition.
AB - INTRODUCTION: Impulsivity and risk-taking behaviours are reported in bipolar
disorder (BD). We examined whether financial management skills are related to
impulsivity in patients with BD. METHODS: We assessed financial management skills
using the Executive Personal Finance Scale (EPFS), impulsivity using the Barratt
Impulsiveness Scale (BIS) and response inhibition using an emotional go/no-go
task in bipolar individuals (N = 21) and healthy controls (HC; N = 23). RESULTS:
Patients had fewer financial management skills and higher levels of impulsivity
than HC. In patients and controls, increased impulsivity was associated with
poorer personal financial management. Patients and HC performed equally on the
emotional go/no-go task. Higher BIS scores were associated with faster reaction
times in HC. In patients, however, higher BIS scores were associated with slower
reaction times, possibly indicating compensatory cognitive strategies to counter
increased impulsivity. CONCLUSIONS: Patients with BD may have reduced abilities
to manage personal finances, when compared against healthy participants.
Difficulty with personal finance management may arise in part as a result of
increased levels of impulsivity. Patients may learn to compensate for increased
impulsivity by modulating response times in our experimental situations although
whether such compensatory strategies generalize to real-world situations is
unknown.
PMID- 26436338
TI - Changes in hydration following haemodialysis estimated with bioimpedance
spectroscopy.
AB - INTRODUCTION: Bioelectrical impedance devices are being more frequently used as
an aid to clinical assessment in helping to determine normo-hydrated weight, or
target weight for haemodialysis patients. Pre-dialysis measurements are more
convenient in clinical practice for patients and staff. We wished to determine
the value of pre-dialysis measurements of over-hydration by comparing post
dialysis values with actual weight loss. METHODS: We measured bioimpedance using
bioimpedance spectroscopy pre-dialysis and then post-dialysis. RESULTS:
Bioimpedance spectroscopy was measured pre-dialysis and post-dialysis in 49
haemodialysis patients, 70% male; mean age 63.9 +/- 17.9 years. Weight fell from
69.5 +/- 17.3 to 67.7 +/- 16.9 kg, P < 0.001, with a fall in mean over-hydration
(OH) from 2.1 +/- 3.4 to 1.3 +/- 2.8 L, P < 0.017, and extracellular water (ECW)
from 17.0 +/- 5.2 to 16.5 +/- 5.0 L, P = 0.03. The change in OH underestimated
weight change (mean bias -1. 1). Change in OH did not correlate with measured
weight loss on univariate analysis (r = 0.26, P = 0.07) but positively correlated
with the change in ECW (r = 0.29, P = 0.046) and negatively with intracellular
water (r = -0.58, P < 0.001). SUMMARY: Although more convenient to make
bioimpedance measurements of hydration status pre-dialysis, we did not find that
changes in OH post-dialysis mirrored the changes in measured weight. As such,
single pre-dialysis bioimpedance measurements of hydration status may not
accurately predict post-dialysis hydration status.
PMID- 26436339
TI - Convergence of multi-valley bands as the electronic origin of high thermoelectric
performance in CoSb3 skutterudites.
AB - Filled skutterudites R(x)Co4Sb12 are excellent n-type thermoelectric materials
owing to their high electronic mobility and high effective mass, combined with
low thermal conductivity associated with the addition of filler atoms into the
void site. The favourable electronic band structure in n-type CoSb3 is typically
attributed to threefold degeneracy at the conduction band minimum accompanied by
linear band behaviour at higher carrier concentrations, which is thought to be
related to the increase in effective mass as the doping level increases. Using
combined experimental and computational studies, we show instead that a secondary
conduction band with 12 conducting carrier pockets (which converges with the
primary band at high temperatures) is responsible for the extraordinary
thermoelectric performance of n-type CoSb3 skutterudites. A theoretical
explanation is also provided as to why the linear (or Kane-type) band feature is
not beneficial for thermoelectrics.
PMID- 26436340
TI - Understanding and predicting the orientation of heteroleptic phosphors in organic
light-emitting materials.
AB - Controlling the alignment of the emitting molecules used as dopants in organic
light-emitting diodes is an effective strategy to improve the outcoupling
efficiency of these devices. To explore the mechanism behind the orientation of
dopants in films of organic host materials, we synthesized a coumarin-based
ligand that was cyclometalated onto an iridium core to form three phosphorescent
heteroleptic molecules, (bppo)2Ir(acac), (bppo)2Ir(ppy) and (ppy)2Ir(bppo) (bppo
represents benzopyranopyridinone, ppy represents 2-phenylpyridinate, and acac
represents acetylacetonate). Each emitter was doped into a 4,4'-bis(N-carbazolyl)
1,1'-biphenyl host layer, and the resultant orientation of their transition
dipole moment vectors was measured by angle-dependent p-polarized
photoluminescent emission spectroscopy. In solid films, (bppo)2Ir(acac) is found
to have a largely horizontal transition dipole vector orientation relative to the
substrate, whereas (ppy)2Ir(bppo) and (bppo)2Ir(ppy) are isotropic. We propose
that the inherent asymmetry at the surface of the growing film promotes dopant
alignment in these otherwise amorphous films. Modelling the net orientation of
the transition dipole moments of these materials yields general design rules for
further improving horizontal orientation.
PMID- 26436341
TI - Three-dimensional macroporous nanoelectronic networks as minimally invasive brain
probes.
AB - Direct electrical recording and stimulation of neural activity using micro
fabricated silicon and metal micro-wire probes have contributed extensively to
basic neuroscience and therapeutic applications; however, the dimensional and
mechanical mismatch of these probes with the brain tissue limits their stability
in chronic implants and decreases the neuron-device contact. Here, we demonstrate
the realization of a three-dimensional macroporous nanoelectronic brain probe
that combines ultra-flexibility and subcellular feature sizes to overcome these
limitations. Built-in strains controlling the local geometry of the macroporous
devices are designed to optimize the neuron/probe interface and to promote
integration with the brain tissue while introducing minimal mechanical
perturbation. The ultra-flexible probes were implanted frozen into rodent brains
and used to record multiplexed local field potentials and single-unit action
potentials from the somatosensory cortex. Significantly, histology analysis
revealed filling-in of neural tissue through the macroporous network and
attractive neuron-probe interactions, consistent with long-term biocompatibility
of the device.
PMID- 26436342
TI - The negative piezoelectric effect of the ferroelectric polymer poly(vinylidene
fluoride).
AB - Piezoelectricity describes interconversion between electrical charge and
mechanical strain. As expected for lattice ions displaced in an electric field,
the proportionality constant is positive for all piezoelectric materials. The
exceptions are poly(vinylidene fluoride) (PVDF) and its copolymers with
trifluoroethylene (P(VDF-TrFE)), which exhibit a negative longitudinal
piezoelectric coefficient. Reported explanations exclusively consider contraction
with applied electric field of either the crystalline or the amorphous part of
these semi-crystalline polymers. To distinguish between these conflicting
interpretations, we have performed in situ dynamic X-ray diffraction measurements
on P(VDF-TrFE) capacitors. We find that the piezoelectric effect is dominated by
the change in lattice constant but, surprisingly, it cannot be accounted for by
the polarization-biased electrostrictive contribution of the crystalline part
alone. Our quantitative analysis shows that an additional contribution is
operative, which we argue is due to an electromechanical coupling between the
intermixed crystalline lamellae and amorphous regions. Our findings tie the
counterintuitive negative piezoelectric response of PVDF and its copolymers to
the dynamics of their composite microstructure.
PMID- 26436343
TI - Cell and Protein Recognition at a Supported Bilayer Interface via In Situ
Cavitand-Mediated Functional Polymer Growth.
AB - Water-soluble deep cavitands embedded in a supported lipid bilayer are capable of
anchoring ATRP initiator molecules for the in situ synthesis of primary amine
containing polymethacrylate patches at the water:membrane interface. These
polymers can be derivatized in situ to incorporate fluorescent reporters, allow
selective protein recognition, and can be applied to the immobilization of
nonadherent cells at the bilayer interface.
PMID- 26436344
TI - Structural Properties and UV-Visible Absorption Spectroscopy of Retinal-pyridyl
CN Re(I) Carbonyl Bipyridine Complex: A Theoretical Study.
AB - The structural, electronic, and optical properties of the all-trans and five cis
conformers of [Re(CO)3(bpy)(ret-pyr-CN)](+) (bpy = 2,2'-bipyridine; ret-pyr-CN =
pyridyl-CN-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-2-n)-none-(2,4,6,8-tetraen)
were studied in solvent by means of density functional theory (DFT) and time
dependent DFT. The isolated retinal-like chromophore ret-pyr-CN was investigated
as well for comparison. By coordination to the complex the two lowest intraligand
(IL) states localized on the retinal group are slightly red-shifted from 627 to
690 nm and from 415 to 450 nm, respectively. Several isomerization pathways are
open upon irradiation of the Re(I) complex by visible light (400-450 nm),
especially to two cis conformers corresponding to the isomerization of the two
double bonds of the retinal-like ligand close to the pyridyl group linked to the
Re(I) fragment. The metal-to-ligand charge transfer states localized either on
the retinal group or on the bpy ligand should play a minor role in the
isomerization process itself but could improve its efficiency via ultra-fast
intersystem crossing.
PMID- 26436346
TI - Speaker Abstracts.
PMID- 26436348
TI - Pearls for optimizing biomedical manuscripts.
PMID- 26436349
TI - Meeting the Eastern perspective in hepatitis B related ACLF.
PMID- 26436350
TI - The treatment of diabetes mellitus of patients with chronic liver disease.
AB - About 80% of patients with liver cirrhosis may have glucose metabolism disorders,
30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that
DM is associated with an increased risk of hepatic complications and death in
patients with liver cirrhosis. DM might contribute to liver damage by promoting
inflammation and fibrosis through an increase in mitochondrial oxidative stress
mediated by adipokines. Based on the above mentioned the effective control of
hyperglycemia may have a favorable impact on the evolution of these patients.
However, only few therapeutic studies have evaluated the effectiveness and safety
of antidiabetic drugs and the impact of the treatment of DM on morbidity and
mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents
and insulin may produce hypoglycemia and lactic acidosis, as most of these agents
are metabolized by the liver. This review discusses the clinical implications of
DM in patients with chronic liver disease. In addition the effectiveness and
safety of old, but particularly the new antidiabetic drugs will be described
based on pharmacokinetic studies and chronic administration to patients. Recent
reports regarding the use of the SGLT2 inhibitors as well as the new incretin
based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor
agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed.
The establishment of clear guidelines for the management of diabetes in patients
with CLD is strongly required.
PMID- 26436351
TI - Drug-induced fatty liver disease: An overview of pathogenesis and management.
AB - Over the past decades, many drugs have been identified, that can potentially
induce steatohepatitis in the predisposed individual. Classically this has been
incriminated to amiodarone, perhexiline, and 4,4'-diethylaminoethoxyhexestrol
(DH), all of which have been found to independently induce the histologic picture
of non-alcoholic steatohepatitis (NASH). Pathogenetic mechanisms of
hepatotoxicity although still evolving, demonstrate that mitochondrial
dysfunction, deranged ATP production and fatty acid catabolism likely play an
important role. Drugs like steroid hormones can exacerbate the pathogenetic
mechanisms that lead to NASH, and other drugs like tamoxifen, cisplatin and
irenotecan have been shown to precipitate latent fatty liver as well. Further
research aiming to elucidate the pathogenesis of drug-induced steatosis and
steatohepatitis is needed in order to better design therapeutic targets.
PMID- 26436352
TI - Prevalence of hepatitis C virus infection among patients undergoing haemodialysis
in Latin America.
AB - Hepatitis C infection is a worldwide problem. The global prevalence of the
hepatitis C virus (HCV) averages 3%. Moreover, its prevalence among patients
undergoing haemodialysis (HD) varies worldwide, ranging from as low as 1% to up
to 70%. There are few data on its prevalence in developing countries, and even
less information is available on HD patients. A literature review revealed that
the prevalence of HCV infection among patients undergoing HD in Latin America
ranges from 4.2 to 83.9%, with most data stemming from Argentina, Brazil, Mexico,
Peru, Chile, Venezuela and Cuba. The most common genotype was genotype 1, and
subtype 1b was the most frequent. The risk factors associated with this condition
were the duration of the HD treatment and blood transfusion before hepatitis C
screening. In addition, HCV RNA detection by polymerase chain reaction is crucial
for the diagnosis of HCV infection in HD patients. Trials using combinations of
new oral antiviral drugs, such as sofosbuvir and combo (ombitasvir, paritaprevir,
ritonavir and dasabuvir), should be the next step in the improvement of care
among HD patients with HCV, because these therapeutic agents apparently do not
require dose adjustment according to renal function. Finally, information on this
subgroup of patients remains unavailable in some countries; therefore, additional
studies are needed to determine the prevalence trend of HCV infection in these
populations.
PMID- 26436353
TI - Prevalence of hepatitis B and C markers in a population of an urban university in
Rio de Janeiro, Brazil: a cross-sectional study.
AB - BACKGROUND AND RATIONALE: Epidemics of hepatitis B and C are a public health
burden, and their prevalence in Brazil varies among regions. We determined the
prevalence of hepatitis markers in an urban university population in order to
support the development of a comprehensive program for HBV immunization and
HBV/HCV diagnosis. Students, employees, and visitors (n = 2,936, 31 years IQR
24.5-50, female = 69.0% and 81.1% with at least 12 years of education) were
enrolled from May to November 2013. Antibodies against hepatitis B surface
antigen (anti-HBs), against hepatitis B core antigen (anti-HBc), and hepatitis B
surface antigen (HBsAg) were detected with enzyme immunoassays and anti-hepatitis
C virus (anti-HCV) antibodies with a chemiluminescence immunoassay. The results
were confirmed with polymerase chain reaction for HCV and nucleic acid
amplification test for hepatitis B virus (HBV). RESULTS: The overall prevalence
of markers among the participants was 0.136% (95% confidence interval [CI]: 0.003
0.270) for HBsAg, 6.44% (95% CI: 5.55-7.33%) for anti-HBc, 50.8% (95% CI: 48.9
52.7%) for anti-HBs > 10 mIU/mL, and 0.44% (95% CI: 0.20-0.68) for anti-HCV.
Almost 30.4% had anti-HBs titers > 100 mIU/mL. Participants with a detectable HCV
viral load (n = 9) were infected with genotype 1a. CONCLUSIONS: In an urban
university population, in which 80% of participants had > 11 years of education,
prevalence increased with age, and self-declared ethnicity for anti-HBc and with
age, marital status and professional activity for anti-HCV antibodies. A
periodical offer of HCV rapid testing should be implemented, and HBsAg rapid
testing should be offered to individuals above 20 years of age.
PMID- 26436354
TI - Diagnostic performance of controlled attenuation parameter for predicting
steatosis grade in chronic hepatitis B.
AB - BACKGROUND & AIMS: A novel controlled attenuation parameter (CAP) using the
signals acquired by the FibroScan(r) has been developed as a method for
evaluating steatosis. The aim of this study is to assess the performance of the
CAP for the detection and quantification of steatosis in patients with chronic
hepatitis B (CHB). MATERIAL AND METHODS: 136 subjects with CHB underwent liver
biopsy and FibroScan(r) within 60 days. CAP was evaluated retrospectively using
raw FibroScan(r) data. Steatosis was graded as follows: S0 (steatosis < 10% of
hepatocytes), S1 (10 to < 30%), S2 (30 to < 60%) or S3 (>= 60%). Performance was
evaluated by area under the receiver operating characteristic (AUROC) curve.
RESULTS: Proportions of each steatosis grade (S0-S3) were 78, 10, 9 and 3%,
respectively. Using univariate analysis, liver stiffness measurement (LMS)
significantly correlated with fibrosis (tau = 0.43; P < 10-10), sex, necro
inflammatory activity, steatosis, age, NASH, and perisinusoidal fibrosis, and
with liver fibrosis (P < 10-8) and perisinusoidal fibrosis (P = 0.008) using
multivariate analysis. CAP correlated with steatosis (tau = 0.38, P < 10-7), body
mass index, NASH, fibrosis and perisinusoidal fibrosis using univariate analysis,
but only steatosis (P < 10-10) and perisinusoidal fibrosis (P = 0.002) using
multivariate analysis. AUROCs for LSM were: 0.77 (0.69-0.85), 0.87 (0.80-0.95),
and 0.93 (0.83-1.00), respectively, for fibrosis stages F >= 2, F >= 3 and F = 4.
AUROCs for CAP were: 0.82 (0.73-0.92), 0.82 (0.69-0.95), and 0.97 (0.84-1.00) for
>= S1, >= S2 and S3 steatosis, respectively. CONCLUSIONS: In conclusion CAP is a
novel, accurate non-invasive tool and may be suitable for detecting and
quantifying steatosis in CHB patients.
PMID- 26436355
TI - Correlation between serum cytokeratin-18 and the progression or regression of non
alcoholic fatty liver disease.
AB - BACKGROUND: Diagnosis of non-alcoholic fatty liver disease (NAFLD) is limited by
the need for liver biopsies. Serum cytokeratin 18 (CK-18) levels have been
investigated as potential biomarkers for the presence of NAFLD and non-alcoholic
steatohepatitis (NASH). Herein, we assessed the correlation between CK-18 levels
and NAFLD progression. MATERIAL AND METHODS: Serum CK-18 levels were estimated
using the M30 antibody enzyme-linked immunosorbent assay in 147 patients
diagnosed with NAFLD. In 72 patients, disease progression was evaluated by
repeated liver biopsy, which was conducted after 4.3 +/- 2.6 years. The
relationship between the CK-18 levels and liver histological findings was
assessed. RESULTS: The CK-18 levels were useful for identifying NAFLD patients
with NAFLD activity scores (NAS) >= 5 (NAS >= 5 vs. <= 4: 675.1 U/L vs. 348.7
U/L; p < 0.0001). A cut-off value of 375 U/L was calculated using the receiver
operating characteristic curve approach, with a specificity and sensitivity of
81.5 and 65%, respectively, for the diagnosis of NASH. Among the 72 patients who
underwent repeated liver biopsy, 11 patients with a progressed NAS also had
significantly increased serum CK-18 levels (p < 0.01); in 30 patients with an
improved NAS, there was a significant improvement in the mean CK-18 levels (p <
0.0001). The 31 patients with static NAS had static CK-18 levels. CONCLUSIONS: In
conclusion, serum CK-18 levels can predict NAS >= 5 in NAFLD patients. In NAFLD
patients, serum CK-18 levels reflect NAS values and correlate with histological
changes, and they appear to be useful indicators of progression and improvement.
PMID- 26436356
TI - Predicting early discharge from hospital after liver transplantation (ERDALT) at
a single center: a new model.
AB - BACKGROUND & RATIONALE: Limited information related to Liver Transplantation (LT)
costs in South America exists. Additionally, costs analysis from developed
countries may not provide comparable models for those in emerging economies. We
sought to evaluate a predictive model of Early Discharge from Hospital after LT
(ERDALT = length of hospital stay <= 8 days). A predictive model was assessed
based on the odds ratios (OR) from a multivariate regression analysis in a cohort
of consecutively transplanted adult patients in a single center from Argentina
and internally validated with bootstrapping technique. RESULTS: ERDALT was
applicable in 34 of 289 patients (11.8%). Variables independently associated with
ERDALT were MELD exception points OR 1.9 (P = 0.04), surgery time < 4 h OR 3.8 (P
= 0.013), < 5 units of blood products consumption (BPC) OR 3.5 (P = 0.001) and
early weaning from mechanical intubation OR 6.3 (P = 0.006). Points in the
predictive scoring model were allocated as follows: MELD exception points
(absence = 0 points, presence = 1 point), surgery time < 4 h (0-2 points), < 5
units of BPC (0-2 points), and early weaning (0-3 points). Final scores ranged
from 0 to 8 points with a c-statistic of 0.83 (95% CI 0.77-0.90; P < 0.0001).
Transplant costs were significantly lower in patients with ERDALT (median $23,078
vs. $28,986; P < 0.0001). Neither lower patient and graft survival, nor higher
rates of short-term re-hospitalization and acute rejection events after discharge
were observed in patients with ERDALT. In conclusion, the ERDALT score identifies
patients suitable for early discharge with excellent outcomes after
transplantation. This score may provide applicable models particularly for
emerging economies.
PMID- 26436357
TI - Evaluation the value of markers for prediction of portal vein thrombosis after
devascularization.
AB - AIM: To evaluate the value of D-dimer and P-selectin in cirrhotic portal
hypertension (PHT) patients for prediction of portal vein thrombosis (PVT) after
devascularization. MATERIAL AND METHODS: 137 patients with cirrhotic PHT who
undergone devascularization from January 2012 to April 2014 were retrospectively
reviewed, all of them were divided into two groups (PVT group and non-PVT group)
by Doppler ultrasonography (DU) examination. The level of D-dimer and P-selectin
was tested during the peri-operative period. RESULTS: 38 patients (27.7%) were
found PVT by DU examination post-operatively. In contrast to the non- PVT group,
the level of D-dimer and P-selectin in the PVT group was much higher
significantly at 1, 3 and 7 days after devascularization (P < 0.05). However, in
the 15 days after surgery, the difference of P-selectin between the two groups
was not significant (P = 0.260). It was shown that the higher sensitivity of the
two markers for PVT was D-dimer, the higher specificity belonged to P-selectin.
The area under receiver operating characteristic (ROC) curve of P-selectin was
the bigger of the two markers. When the two markers were combined to be used to
diagnose PVT, the sensitivity was increased to 0.911, with a slight drop of
specificity to 0.715, the area under ROC curve was 0.919. CONCLUSION: The level
of D-dimer and P-selectin might be good candidate predictive markers for PVT in
patients with cirrhotic PHT after devascularization. The combined test of the two
markers can increase the value of prediction.
PMID- 26436358
TI - The burden of cirrhosis and impact of universal coverage public health care
system in Thailand: Nationwide study.
AB - BACKGROUND AND RATIONALE: Cirrhosis is responsible for significant health-care
costs and morbidity. This study aims to evaluate the burden of illness associated
with cirrhosis, its impact on the universal coverage public health care system in
Thailand. MATERIAL AND METHODS: We used data from the 2010 Nationwide Hospital
Admission Data, the National Health Security Office (NHSO), Thailand. Their
baseline characteristics, hospital costs, and outcomes were analyzed according to
national health insurance categories including medical welfare scheme (MWFS),
social security scheme (SSS) and civil servant medical benefit scheme (CSMBS).
RESULTS: 92,301 admissions were eligible for analysis. The mean age was 55 +/-
12.8 years, and 63.3% of patients were above 50 years old. The majority of
patients (79%) belonged to the MWFS group. The MWFS group incurred the lowest
medical expense and had the shortest hospital stay compared to the SSS and CSMBS
groups. Overall in-hospital mortality was 10.7%. Cirrhosis complications include
bleeding esophageal varices, spontaneous bacterial peritonitis, hepatic
encephalopathy, hepatorenal syndrome, and hepatocellular carcinoma. These
complications significantly increased mortality rates compared to patients
without complications (26 vs. 8.9%, p < 0.001). In-hospital mortality of patients
with cirrhosis complications did not differ among the three national health
insurance groups. Respiratory failure and septicemia were associated with the
highest risk of death (HR 5.4; 95% CI: 4.8-5.9 and HR 5.2; 95% CI: 4.9-5.6
respectively; P < 0.001). CONCLUSIONS: Illness associated with cirrhosis is a
significant public health problem in Thailand. Outcomes of cirrhosis
complications did not differ between universal public health care coverage
systems in Thailand.
PMID- 26436359
TI - A simple diagnostic index comprising epithelial membrane antigen and fibronectin
for hepatocellular carcinoma.
AB - Background and rationale for the study. Continuing search for suitable tumor
markers is of clinical value in managing patients with various malignancies.
These markers may be presented as intracellular substances in tissues or may be
released into the circulation and appear in serum. Therefore, this work is
concerned with identification and quantitative determination of epithelial
membrane antigen (EMA) and fibronectin and estimating their performances as
surrogate markers for identifying hepatocellular carcinoma (HCC). RESULTS: A
total of 627 individuals constituted this study [fibrosis (F1-F3) = 217;
cirrhosis = 191; HCC = 219]. Western-blot was used for identifying EMA and
fibronectin in sera. As a result, a single immunoreactive band was shown at 130
kDa and 90-kDa corresponding to EMA and fibronectin, respectively. They were
quantified using ELISA providing values in HCC higher than fibrosis or cirrhosis
with a significant difference (P < 0.0001). For identifying HCC, EMA showed 0.82
area under receiver-operating characteristic curve (AUC) with sensitivity = 70%
and specificity = 78% while fibronectin yielded AUC = 0.70 with sensitivity = 67%
and specificity = 82%. FEBA-Test comprising fibronectin and EMA together with
total-bilirubin and AFP was constructed yielding AUC = 0.92 for identifying HCC
from cirrhosis with sensitivity = 89% and specificity = 85%. FEBA-Test was then
tested for differentiating HCC from fibrosis showing AUC = 0.97 with sensitivity
= 90% and specificity = 89%. FEBA-Test enabled the correct identification of HCC
patients with CLIP 0-1 and size <= 3 cm with AUC = 0.80 and AUC = 0.84,
respectively, indicating its ability in identifying early HCC. CONCLUSIONS: A
four-marker index may improve the early detection of HCC with a high degree of
accuracy.
PMID- 26436360
TI - Evaluation of alpha-fetoprotein as a screening marker for hepatocellular
carcinoma in hepatitis prevalent areas.
AB - The objective of this study was to establish modified cutoff values of serum
alpha-fetoprotein (AFP) according to hepatitis status. While AFP is used as a
serum marker in the diagnosis or monitoring of hepatocellular carcinoma (HCC),
its use as a screening method to the general population is controversial. We
evaluated its screening performance in a hepatitis prevalent East Asian
population, and suggest different cutoff values according to the individual's
hepatitis status. We evaluated the performance of AFP as a screening test in
48,123 consecutive Koreans during the period from March, 2012 to August, 2013 who
underwent routine health checks at a single institution. Sensitivity,
specificity, positive predictive value (PPV), and negative predictive value (NPV)
were calculated with fixed cutoff and with modified cutoffs according the
individual's hepatitis status. A total of 24 out of 48,123 subject (0.05%) were
newly diagnosed with HCC after screening. Among the 1,874 subject with positive
hepatitis B virus surface antigen (HBsAg), 17 (0.91%) developed HCC, compared
with two out of 393 (0.51%) individuals with hepatitis C virus antibody (anti
HCV). Five out of 45,855 (0.01%) subject with neither HBsAg nor anti-HCV
developed HCC. Compared to the performance of a fixed cutoff, specificity, PPV,
and NPV improved without sacrificing sensitivity when applying modified cutoff.
In conclusion, our findings suggest that AFP with modified cutoffs according to
the individual's hepatitis status might be a useful screening marker for HCC in
hepatitis prevalent areas.
PMID- 26436361
TI - Drug-induced liver injury in hospitalized HIV patients: high incidence and
association with drugs for tuberculosis.
AB - BACKGROUND: The evaluation of liver disease in HIV patients is cumbersome because
may result from a number of different causes. The aim of this retrospective study
was to estimate the incidence of severe drug induced liver injury (DILI) in a
group of HIV inpatients and investigate potential risk factors. MATERIAL AND
METHODS: We performed a retrospective analysis of data from HIV-infected patients
hospitalized between August 2010 and August 2011 in a tertiary hospital in Sao
Paulo, Brazil. Severe hepatotoxicity was defined as grade 3 (5.1 to 10 x ULN) or
4 (> 10 x ULN) of ALT and AST levels. Factors analyzed included demographics,
infection with hepatitis viruses, alcohol history and use of hepatotoxic drugs
prior to or during hospital admission. RESULTS: A total of 149 patients with HIV
were hospitalized during the study period. The majority were male over 42 years
of age and 82 (55%) were taking HAART initiated prior to admission. Mean CD4
counts were 164 cells/mm3. Thirty three patients (22.1%) developed severe DILI
during hospital stay, which had a mean duration of 26 days. Factors associated
with severe DILI in the multivariate analysis were abnormal baseline ALT levels
[OR 2.02 (95%CI 1.13-3.59); p = 0.017] and tuberculosis therapy [OR 2.31 (95% CI
1.27-4.19); p = 0.006]. In conclusion, in this group of HIV patients admitted to
a tertiary hospital in Brazil, we found a high incidence (22.1%) of severe DILI.
The use of anti-tuberculosis drugs and baseline liver injury were independent
factors associated with severe DILI during hospital stay.
PMID- 26436362
TI - Contrast-induced acute kidney injury in cirrhotic patients. A retrospective
analysis.
AB - BACKGROUND: The nephrotoxic potential of intravenous iodinated contrast (IC) is
controversial. Cirrhotic patients are often submitted to imaging procedures
involving IC and small changes in renal function may have detrimental effects.
MATERIAL AND METHODS: Retrospective analysis of hospitalized patients with
elective imaging by either contrast-enhanced CT or MRI. Contrast induced acute
kidney injury (CI-AKI) was diagnosed if there was either an increase of SCr by
25% or by 44 MUmol/L or a decrease of estimated glomerular filtration rate by 25%
by day 3. RESULTS: Between 2004 and 2012 152 patients (female: 30.3%, age: 60 +/-
10.8 years, MELD 13 +/- 6) were included in this study of which 84 (55.3%) had
received IC and 68 (44,7%), who served as controls, MRI with gadolinium based
contrast (non-IC). Baseline parameters were well matched except for age (61.7 vs.
56.9) years in the IC vs. non-IC groups, p = 0.005). 15 patients (17.9%)
receiving IC and 4 patients (5.9%) not receiving IC (p = 0.026) reached the
composite end-point for CI-AKI. In multivariable regression analysis INR [B =
0.252 (95% CI: 0.108-0.397), p = 0.001]; IC [B = 0.136 (95% CI: 0.023-0.248), p =
0.019] and serum sodium [B = 0.011 (95% CI: 0.001-0.023); p = 0.080] were
independently associated with changes of SCr. In conclusion IC may cause renal
dysfunction in cirrhotic patients. Patients subjected to imaging using IC should
be closely monitored.
PMID- 26436363
TI - The limited prognostic value of liver histology in children with biliary atresia.
AB - Background and rationale for the study. The aim of the study was to determine the
prognostic value of histopathological findings with special care to the severity
of liver fibrosis at the moment of hepatoportoenterostomy (HPE) in children with
biliary atresia (BA). We performed analysis of 142 wedge liver biopsies taken at
the time of HPE. All patients were operated by the same surgical team between
1995 and 2007. According to the outcome 6 months after HPE patients were divided
into prognostic groups: group 1-bilirubin level < 2 mg% (n = 65), group 2
bilirubin level > 2 mg% (n = 77). Liver biopsies were re-evaluated according to
the extended histopathological protocol and then were compared between the
prognostic groups. Survival with native liver (SNL) estimates were performed in
regard to severity of liver fibrosis. RESULTS: Survival with native liver
estimates after 2, 5 and 10 years in patients after successful operation were
96%, 91%, 75% vs. 30%, 11%, and 5% if operation failed (p < 0.001). There was no
difference between groups in the following variables: fibrosis (p = 0.69), portal
inflammation (p = 0.99), lobular inflammation (p = 0.95), cholangiolitis (p =
0.23), accumulation of bile pigments (zone 1:p = 0.49; zone 2:p = 0.51; zone 3:p
= 0.48), bile plugs in canaliculi (p = 0.12), bile plugs in ducts (p = 0.32),
bilirubinostasis in hepatocytes (p = 0.45), bile ductular proliferation (p =
0.59), ductal plate malformation (p = 0.12), focal necrosis (p = 0.44), giant
cell transformation (p = 0.45), haematopoesis (p = 0.52), ductopenia (p = 0.46),
microabscesses (p = 0.49), ballooning of hepatocytes (p = 0.08). The actuarial
5/10-year SNL was not dependent on severity of liver fibrosis (log-rank test p =
0.84). The severity of fibrosis corresponded neither with the age at HPE nor with
the laboratory findings before operation but increased the risk of portal
hypertension. CONCLUSION: Liver histology at the time of HPE is of limited value
in prognosis making in BA.
PMID- 26436364
TI - Maternal separation on the ethanol-preferring adult rat liver structure.
AB - Background and rationale for the study. We designed to test whether there is
interaction of maternal separation (MS) on the ethanol-preferring rats liver
structure. The UCh rat pups were separated daily from their mothers during the
stress hyporesponsive period (SHRP), between four and 14 days-old, always at the
same time for four hours in a cage containing eight subdivisions, one for each
pup. Subsequently, rats that presented the highest (UChB) and the lowest (UChA)
ethanol (EtOH) consumption were selected to the study. Both UChB and UChA rats
received 10% (v/v) EtOH and distilled water ad libitum until the end of the
experiment (120 days-old). The liver was collected to histological routine for
morphometric and stereological analyses, and immunohistochemistry. RESULTS: There
was an interaction of MS and EtOH on the liver: increased liver mass, peritubular
vessels, stellate cell numbers, steatosis and cell death, decreased necrosis,
sinusoidal capillary diameters and cell proliferation. While there was a decrease
in FSH, testosterone and 5alpha-di-hidrotestosterone, and increasing
corticosterone and cholesterol. CONCLUSIONS: There is interaction of MS and EtOH
on the liver structure, dependent on the amount of EtOH intake. Furthermore, the
interaction of stress and drugs can increase or decrease their effects on the
liver or indirectly via hypothalamic-pituitary-adrenal (HPA) and hypothalamic
pituitary-gonadal (HPG) axes.
PMID- 26436365
TI - Congenital double intrahepatic portosystemic shunt: Imaging findings and
endovascular closure.
PMID- 26436366
TI - Severe hypercholesterolemia mediated by lipoprotein X in a patient with
cholestasis.
AB - Lipoprotein X (LpX) is an abnormal lipoprotein associated with cholestasis. It is
a significant cause of severe hypercholesterolemia and should always be
considered in patients with cholestatic liver disease. This case highlights the
significance of LpX as a cause of severe hypercholesterolemia in a patient with
cholestasis secondary to a granulomatous hepatitis attributed to tuberculosis.
Lipoprotein agarose gel electrophoresis and gradient gel electrophoresis were
performed for the detection of LpX. The liver function tests, electrolytes, lipid
profile and bile acids were also determined. Anti-tuberculous therapy was
initiated and the liver functions improved with normalisation of the lipid
profile.
PMID- 26436367
TI - Peritoneal ultrafiltration for refractory fluid overload and ascites due to
pulmonary arterial hypertension.
AB - Pulmonary hypertension is a common finding in patients with advanced liver
disease. Similarly, among patients with advanced pulmonary arterial hypertension,
right heart failure leads to congestive hepatopathy. Diuretic resistant fluid
overload in both advanced pulmonary hypertension and chronic liver disease is a
demanding challenge for physicians. Venous congestion and ascites-induced
increased intra-abdominal pressure are essential regarding recurrent
hospitalization, morbidity and mortality. Due to impaired right-ventricular
function, many patients cannot tolerate extracorporeal ultrafiltration.
Peritoneal dialysis, a well-established, hemodynamically tolerated treatment for
outpatients may be a good alternative to control fluid status. We present a
patient with pulmonary arterial hypertension and congestive hepatopathy
hospitalized for over 3 months due to ascites induced refractory volume overload
treated with peritoneal ultrafiltration. We report the treatment benefits on
fluid balance, cardiorenal and pulmonary function, as well as its safety. In
conclusion, we report a case in which peritoneal ultrafiltration was an efficient
treatment option for refractory ascites in patients with congestive hepatopathy.
PMID- 26436368
TI - Isolated liver disease in a patient with a CFTR genotype F508del/12TG-5T and
470MV: A new face of an old disease.
AB - Today the knowledge of genotype-phenotype correlation in cystic fibrosis is
enriched by the growing discoveries of new mutations of the CFTR gene. Although
the combination of two severe mutations usually leads to the classic disease
(pulmonary and pancreatic insufficiency, sterility, nasal polyposis), the
presence of a complex genotype characterized by severe and milder mutations or
polymorphism can cause a hidden disease, which is often asymptomatic at early
ages. We report on a case of a 15 years old boy, in whom the only clinical signs
of CF were chronic hypertransaminasemia and hyperbilirubinemia, and in whom it
was demonstrated the presence of the mutations F508del associated with TG11-9T
470M in one allele and TG12-5T-470V in the other allele. Although a clear
genotype-phenotype correlation for liver disease is still missing for CF
patients, it is possible to state that this isolated clinical presentation could
represent an unusual phenotype of CF, related to a complex genotype characterized
by a severe mutation and one (or more) polymorphism.
PMID- 26436369
TI - Assessing risk factors of acute kidney injury after liver transplantation.
PMID- 26436370
TI - Acute kidney injury after liver transplantation is associated with viral
hepatitis, prolonged warm ischemia, serum lactate and higher mortality.
PMID- 26436371
TI - Nonalcoholic fatty liver disease and polycystic ovary syndrome.
PMID- 26436372
TI - Slow growth of the overexploited milk shark Rhizoprionodon acutus affects its
sustainability in West Africa.
AB - Age and growth of Rhizoprionodon acutus were estimated from vertebrae age bands.
From December 2009 to November 2010, 423 R. acutus between 37 and 112 cm total
length (LT ) were sampled along the Senegalese coast. Marginal increment ratio
was used to check annual band deposition. Three growth models were adjusted to
the length at age and compared using Akaike's information criterion. The Gompertz
growth model with estimated size at birth appeared to be the best and resulted in
growth parameters of Linfinity = 139.55 (LT ) and K = 0.17 year(-1) for females
and Linfinity = 126.52 (LT ) and K = 0.18 year(-1) for males. The largest female
and male examined were 8 and 9 years old, but the majority was between 1 and 3
years old. Ages at maturity estimated were 5.8 and 4.8 years for females and
males, respectively. These results suggest that R. acutus is a slow-growing
species, which render the species particularly vulnerable to heavy fishery
exploitation. The growth parameters estimated in this study are crucial for stock
assessments and for demographic analyses to evaluate the sustainability of
commercial harvests.
PMID- 26436373
TI - Macroecological analysis of the fish fauna inhabiting Cymodocea nodosa seagrass
meadows.
AB - In this study, patterns in the taxonomic richness and composition of the fish
fauna inhabiting Cymodocea nodosa seagrass meadows were described across their
entire distribution range in the Mediterranean Sea and adjacent Atlantic Ocean.
Specifically, the study tested whether there are differences in the composition
of fish assemblages between those ecoregions encompassed by the distribution
range of C. nodosa, and whether these differences in composition are connected
with differences in bioclimatic affinities of the fish faunas. A literature
review resulted in a total of 19 studies, containing 22 fish assemblages at 18
locations. The ichthyofauna associated with C. nodosa seagrass meadows comprises
59 families and 188 species. The western Mediterranean (WM) Sea has the highest
species richness (87 species). Fish assemblages from the Macaronesia-Canary
Islands, the Sahelian Upwelling, South European Atlantic Shelf and the WM differ,
in terms of assemblage composition, relative to other ecoregions. In contrast,
the composition of the fish fauna from the central and eastern Mediterranean
overlaps. There is a significant serial correlation in fish assemblage
composition between adjacent ecoregions along the distribution range of C.
nodosa. Dissimilarities in assemblage composition are connected with the
geographical separation between locations, and the mean minimum annual seawater
temperature is the environmental factor that explains most variation in fish
assemblage composition.
PMID- 26436375
TI - Genetic diversity and genetic structure of consecutive breeding generations of
golden mandarin fish (Siniperca scherzeri Steindachner) using microsatellite
markers.
AB - In this study, 12 polymorphic microsatellites were inves-tigated to determine the
genetic diversity and structure of 5 consecu-tive selected populations of golden
mandarin fish (Siniperca scherzeri Steindachner). The total numbers of alleles,
average heterozyosity, and average polymorphism information content showed that
the genetic diversity of these breeding populations was decreasing. Additionally,
pairwise fixation index FST values among populations and Da values in-creased
from F1 generation to subsequent generations (FST values from 0.0221-0.1408; Da
values from 0.0608-0.1951). Analysis of molecular variance indicated that most
genetic variations arise from individuals within populations (about 92.05%),
while variation among populations accounted for only 7.95%. The allele frequency
of the loci SC75-220 and SC101-222 bp changed regularly in the 5 breeding
generations. Their frequencies were gradually increased and showed an enrichment
trend, indicating that there may be genetic correlations between these 2 loci and
breeding traits. Our study indicated that microsatellite markers are effective
for assessing the genetic variability in the golden mandarin fish breeding
program.
PMID- 26436374
TI - Differential submitochondrial localization of PINK1 as a molecular switch for
mediating distinct mitochondrial signaling pathways.
AB - Mutations in mitochondrial kinase PINK1 cause Parkinson disease (PD), but the
submitochondrial site(s) of PINK1 action remains unclear. Here, we report that
three-dimensional structured illumination microscopy (3D-SIM) enables super
resolution imaging of protein submitochondrial localization. Dual-color 3D-SIM
imaging analysis revealed that PINK1 resides in the cristae membrane and
intracristae space but not on the outer mitochondrial membrane (OMM) of healthy
mitochondria. Under normal physiological conditions, PINK1 colocalizes with its
substrate TRAP1 in the cristae membrane and intracristae space. In response to
mitochondrial depolarization, PINK1, but not TRAP1, translocates to the OMM. The
PINK1 translocation to the OMM of depolarized mitochondria is independent of new
protein synthesis and requires combined action of PINK1 transmembrane domain and
C-terminal region. We found that mitochondrial depolarization-induced PINK1 OMM
translocation is required for recruitment of parkin to the OMM of damaged
mitochondria. Our findings suggest that differential submitochondrial
localization of PINK1 serves as a molecular switch for mediating two distinct
mitochondrial signaling pathways in maintenance of mitochondrial homeostasis.
Furthermore, our study provides evidence for the involvement of deregulated PINK1
submitochondrial localization in PD pathogenesis.
PMID- 26436376
TI - Changes and clinical significance of serum vaspin levels in patients with type 2
diabetes.
AB - We investigated serum visceral adipose tissue-derived serpin (vaspin) levels in
patients with normal glucose regulation and recently diagnosed type 2 diabetes
(T2DM) and explored the association between vaspin and body mass index, age,
gender, glucose, lipid metabolism, and insulin sensitivity. Fasting serum vaspin
levels in 66 patients with T2DM and 48 normal subjects were detected using enzyme
linked immunosorbent assay. We found that serum vaspin levels in the DM group
were 0.65 +/- 0.13 mg/L in non-obese patients and 1.13 +/- 0.25 mg/L in obese
patients. Serum vaspin levels in the control group were 0.38 +/- 0.18 mg/L in non
obese patients and 0.95 +/- 0.11 mg/L in obese patients. Average serum vaspin
levels were significantly higher in obese patients than in non-obese patients in
both the DM group and control group. In the DM group, the serum vaspin level was
0.76 +/- 0.22 mg/L in males and 0.92 +/- 0.35 mg/L in females. In the control
group, the serum vaspin level was 0.48 +/- 0.14 mg/L in males and 1.05 +/- 0.21
mg/L in females. Association analysis showed that serum vaspin levels were
significantly associated with body mass index, waist-to-rip ratio (WHR), fat
percentage, triglyceride, fasting plasma insulin, and insulin sensitivity index.
Stepwise multiple regression analysis showed that gender, insulin sensitivity
index, and WHR were the most significant independent factors affecting vaspin.
Therefore, serum vaspin levels were significantly elevated in obese people and
were independently associated with WHR, gender, and index sensitivity index.
PMID- 26436377
TI - Effect of RAGE polymorphisms on susceptibility to and severity of osteoarthritis
in a Han Chinese population: a case-control study.
AB - Recent studies have revealed that the inflammatory process plays a role in the
pathogenesis of osteoarthritis (OA). The S100 family and receptor for advanced
glycation end products (RAGE) participate in regulating inflammation, even in the
production of matrix metalloproteinases (MMPs). MMP-1 degrades cartilage, which
may result in OA development. Moreover, polymorphisms in RAGE, S100A8, and MMP-1
have a marked effect on ligand binding and transcription regulating. In this
study, we investigated the potential genetic contribution of the RAGE, S100A8,
and MMP-1 genes to OA. We performed a matched case-control association study and
genotyped OA patients and healthy controls, who were analyzed by polymerase chain
reaction-restriction fragment length polymorphism assays. A total of 207 patients
were diagnosed with knee OA and underwent total knee replacement. The control
group included 207 individuals who had standard X-rays of the knee joints to
confirm K/L < 2 and were matched by age and gender. Single-nucleotide
polymorphisms in RAGE (-429T/C, -374T/A, and 557G/A), S100A8 (rs3795391A/G), and
MMP-1 (-1607 1G/2G, -755G/T, and -519A/G) were evaluated. RAGE -374T/A, S100A8
rs3795391A/G, MMP-1 -1607 1G/2G, -755G/T, and -519A/G showed no significant
difference between OA patients and healthy controls. RAGE -429T/C and 557G/A
showed a significant association between OA patients and healthy controls (P =
0.016 and 0.047, respectively). In haplotype analyses, no RAGE and MMP-1
haplotypes showed associations with OA. Our results suggest that the investigated
polymorphism in the RAGE gene play a role in OA in the Han Chinese population.
PMID- 26436378
TI - Expressional analysis of immune-related miRNAs in breast milk.
AB - Immune-related miRNAs in breast milk are extracellular miRNAs that are related to
immune organ development and regulation of the immune function in infants and
young animals. The goal of this study was to compare the expression levels of
five immune-related miRNAs in breast milk in black goats, humans, and dairy
cattle. The miRNAs from milk were extracted and the expression levels were
assessed using quantitive RT-PCR methods. MiR-146, miR-155, miR-181a, miR-223,
and miR-150 were all detected in Dazu black goat milk, and these miRNAs were
significantly more highly expressed in colostrum than in mature milk of goats (P
< 0.01), except for miR-150. Further, all five miRNAs were expressed in human
colostrum, but patterns differed from those in goats: miR-146 and miR-155 were
highly expressed (P < 0.01) in human colostrum, whereas miR-223 was abundant in
goat colostrum (P < 0.01). In addition, five miRNAs were significantly higher in
bovine mature milk than in goat milk (P < 0.01). Taken together, these results
confirm that immune-related miRNAs are rich in breast milk with different
expression levels depending on the lactation phase and species.
PMID- 26436379
TI - Identification of single nucleotide polymorphisms in the ASB15 gene and their
associations with chicken growth and carcass traits.
AB - ASB15 is a member of the ankyrin repeat and suppressor of cytokine signaling box
family, and is predominantly expressed in skeletal muscle. In the present study,
an F2 resource population of Gushi chickens crossed with Anka broilers was used
to investigate the genetic effects of the chicken ASB15 gene. Two single
nucleotide polymorphisms (SNPs) (rs315759231 A>G and rs312619270 T>C) were
identified in exon 7 of the ASB15 gene using forced chain reaction-restriction
fragment length polymorphism and DNA sequencing. One was a missense SNP
(rs315759231 A>G) and the other was a synonymous SNP (rs312619270 T>C). The
rs315759231 A>G polymorphism was significantly associated with body weight at
birth, 12-week body slanting length, semi-evisceration weight, evisceration
weight, leg muscle weight, and carcass weight (P < 0.05). The rs312619270 T>C
polymorphism was significantly associated with body weight at birth, 4, 8, and 12
week body weight, 8-week shank length, 12-week breast bone length, 8 and 12-week
body slanting length, breast muscle weight, and carcass weight (P < 0.05). Our
results suggest that the ASB15 gene profoundly affects chicken growth and carcass
traits.
PMID- 26436380
TI - Molecular typing of Salmonella from Sergipe, Northeastern Brazil, showing the
epidemiological relationship between poultry and human infection.
AB - Randomly amplified polymorphic DNA (RAPD) has been widely used for
epidemiological and phylogenetic purposes ow-ing to its rapidity and efficiency.
The aim of this study was to perform genome typing of Salmonella samples isolated
from different sources by RAPD profiling. Thirty-three Salmonella samples from
the bacterial collection of the Laboratorio de Virologia Comparada, Departamento
de Morfologia, Universidade Federal de Sergipe, Brazil, and two standard samples
were used. RAPD profiling was conducted using six primers of the Ready-To-Go RAPD
system. The amplified products were electro-phoresed on 5% polyacrylamide gel and
silver-stained. RAPD analysis resulted in reproducible and stable banding
patterns and showed high genetic diversity among the isolated strains. The Primer
P1-generated dendrogram showed an epidemiologic relationship between the human
and poultry isolated samples, highlighting the usefulness of RAPD for molecular
typing and epidemiological studies.
PMID- 26436381
TI - Effects of glucose and disorders in lipid metabolism on cytokine levels and
cognitive impairment in the olanzapine-induced obesity rat model.
AB - The aim of the study was to explore the effects of increased levels of blood
sugar and cytokines on impaired cognitive function in the olanzapine-induced
obesity rat model. A total of 40 rats were randomly divided into 2 groups; the
control and olanzapine groups (N = 20 per group). The control rats were fed
regular food, while the olanzapine rats received olanzapine-enriched (1.2 mg/kg)
food by gavage for 4 weeks to establish the olanzapine-induced obese rat model.
Enzyme-linked immunosorbent assays were used to measure the serum levels of tumor
necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein
(CRP). Serum glucose content was measured by biochemical colorimetry. Learning
and memory capacity was measured using a Y-maze, and the time before escape from
a Morris water maze was recorded. Body weight and levels of blood glucose,
lipids, TNF-alpha, IL-6, and CRP increased in the olanzapine group. In addition,
the number of shocks received before reaching the learning and memory standard
and the time before escape from the Morris water maze were higher in the
olanzapine group than in the control group. Olanzapine causes disorders in
glucose and lipid metabolism. Increase in blood glucose promotes the toxicity of
cytokines and leads to cognitive dysfunction in rats.
PMID- 26436382
TI - Sequence variation in ROP8 gene among Toxoplasma gondii isolates from different
hosts and geographical localities.
AB - The protozoan parasite Toxoplasma gondii has a worldwide distribution; it can
cause serious diseases in humans and almost all other warm-blooded animals.
Different genotypes of T. gondii result in different lesions in the same host. T.
gondii rhoptry protein 8 (TgROP8) is a major factor of T. gondii acute virulence.
We examined sequence variation in the TgROP8 gene among T. gondii isolates from
different hosts and geographical localities. The TgROP8 gene was amplified from
individual isolates and sequenced. A phylogenetic tree was constructed using
Bayesian inference, maximum parsimony, and maximum likelihood based on the
sequences obtained plus TgME49 from the ToxoDB database. The TgROP8 gene was 1728
bp in length for all the examined T. gondii strains, and their A+T contents were
45.37-45.95%. Sequence analysis detected 140 (0.06-5.56%) variable nucleotide
positions resulting in 96 (0-10.78%) amino acid substitutions. Sequence
variations in the TgROP8 gene resulted in polymorphic restriction sites for
endonucleases BstBI, BsaI, and XhoI, which allowed the differentiation of the
three classical genotype strains (types I, II, and III) by polymerase chain
reaction-restriction fragment length polymorphism (PCR-RFLP). However,
phylogenetic analyses indicated that the TgROP8 gene is not a suitable genetic
marker for population studies of T. gondii.
PMID- 26436383
TI - Evaluation of microsatellite loci from libraries derived from the wild diploid
'Calcutta 4' and 'Ouro' banana cultivars.
AB - Microsatellite markers have been widely used in the quantification of genetic
variability and for genetic breeding in Musa spp. The objective of the present
study was to evaluate the discriminatory power of microsatellite markers derived
from 'Calcutta 4' and 'Ouro' genomic libraries, and to analyze the genetic
variability among 30 banana accessions. Thirty-eight markers were used: 15 from
the 'Ouro' library and 23 from the 'Calcutta 4' library. Genetic diversity was
evaluated by considering SSR markers as both dominant markers because of the
presence of triploid accessions, and co-dominant markers. For the dominant
analysis, polymorphism information content (PIC) values for 44 polymorphic
markers ranged from 0.063 to 0.533, with a mean value of 0.24. A dendrogram
analysis separated the BGB-Banana accessions into 4 groups: the 'Ouro' and 'Muisa
Tia' accessions were the most dissimilar (93% dissimilarity), while the most
similar accessions were 'Pacovan' and 'Walha'. The mean genetic distance between
samples was 0.74. For the analysis considering SSR markers as co-dominants, using
only diploid accessions, two groups were separated based on their genome contents
(A and B). The PIC values for the markers from the 'Calcutta 4' library varied
from 0.4836 to 0.7886, whereas those from the 'Ouro' library ranged from 0.3800
to 0.7521. Given the high PIC values, the markers from both the libraries showed
high discriminatory power, and can therefore be widely applied for analysis of
genetic diversity, population structures, and linkage mapping in Musa spp.
PMID- 26436384
TI - Apoptosis induced by lipid-associated membrane proteins from Mycoplasma
hyopneumoniae in a porcine lung epithelial cell line with the involvement of
caspase 3 and the MAPK pathway.
AB - Lipid-associated membrane proteins (LAMPs) are important in the pathogenicity of
the Mycoplasma genus of bacteria. We investigated whether Mycoplasma
hyopneumoniae LAMPs have pathogenic potential by inducing apoptosis in a St. Jude
porcine lung epithelial cell line (SJPL). LAMPs from a pathogenic strain of M.
hyopneumoniae (strain 232) were used in the research. Our investigation made use
of diamidino-phenylindole (DAPI) and acridine orange/ethidium bromide (AO/EB)
staining, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end
labeling (TUNEL) analysis, and Annexin-V-propidium iodide staining. After LAMP
treatment for 24 h, typical changes were induced, chromosomes were concentrated,
apoptotic bodies were observed, the 3'-OH groups of cleaved genomes were exposed,
and the percentage of apoptotic cells reached 36.5 +/- 11.66%. Caspase 3 and
caspase 8 were activated and cytochrome c (cyt c) was released from the
mitochondria into the cytoplasm; poly ADP ribose polymerase (PARP) was digested
into two fragments; p38 mitogen-activated protein kinase (MAPK) was
phosphorylated; and the expression of pro-apoptosis protein Bax increased while
the anti-apoptosis protein Bcl-2 decreased. LAMPs also stimulated SJPL cells to
produce nitric oxide (NO) and superoxide. This study demonstrated that LAMPs from
M. hyopneumoniae can induce apoptosis in SJPL cells through the activation of
caspase 3, caspase 8, cyt c, Bax, and p38 MAPK, thereby contributing to our
understanding of the pathogenesis of M. hyopneumoniae, which should improve the
treatment of M. hyopneumoniae infections.
PMID- 26436385
TI - Suppression of lentivirus-mediated transgenic dendritic cells in graft-versus
host disease after allogeneic bone marrow transplantation in mice.
AB - We determined whether genetically engineered immature dendritic cells (imDCs)
mediated by lentiviral vectors alleviate acute graft-versus-host disease (GVHD)
after allogeneic bone marrow transplantation (allo-BMT) in mice. We introduced
the mouse chemokine receptor 7 (Ccr7) gene into the bone marrow-derived imDCs of
C57BL/6 mice to construct genetically engineered imDCs. A 1:1 mixture of bone
marrow and spleen cells from the donors was injected into the recipients, which
were divided into four groups: radiation, transplantation, empty vector, and
transgenic imDC groups. Symptoms, clinical scores, GVHD pathological changes, and
survival times and rates of recipients were recorded; secretion of IFN-gamma and
IL-4, and allogeneic chimerism rates were detected. The survival time of the
transgenic imDC group (27.5 +/- 7.55 days) was significantly longer than in the
other three groups (P < 0.01). The GVHD score of the imDC group mice was
significantly lower than in the transplantation and empty vector groups (P <
0.05), which meant that mice in the transgenic imDC group had the lightest
pathology damage in the target organs. In the transplantation group, IFN-gamma
increased while IL-4 decreased. In contrast, IFN-gamma decreased and IL-4
increased in both empty vector and trans-imDC groups, and the difference was
significant in the latter (P < 0.01). Thirty days or more following
transplantation, the allogeneic chimerism rate was still 95-100%, suggesting
complete donor type implantation. Ccr7 transfection into imDCs suppressed
occurrence and severity of acute GVHD after allo-BMT in mice; the mechanism might
be associated with IFN-gamma decrease and IL-4 increase.
PMID- 26436386
TI - Resistance of Castanea mollissima Shuhe-WYL strain to Dryocosmus kuriphilus and
its molecular mechanism.
AB - The resistance of Castanea mollissima Shuhe-WYL strain to Dryocosmus kuriphilus
and its molecular mechanism were examined. The larvae of D. kuriphilus were
inoculated on the Shuhe-WYL and Qingzha strains, and mortality was observed and
compared; the relative mRNA content of the OsCDPK2, receptor-like protein, OsNAC6
protein, KH domain protein, RNA-binding protein, and the bHLH genes was detected
using real-time polymerase chain reaction, and then compared between the Shuhe
WYL and Qingzha strains. Phenylalanine ammonia-lyase content was detected by
western blotting and compared between the inoculated Shuhe-WYL, non-inoculated
Shuhe-WYL, and inoculated Qingzha strains. The mortalities of larvae inoculated
on the bud, bracteal leaf, and cardiac lobe were lower in Shuhe-WYL than Qingzha
at 48 and 96 h after inoculation; the contents of OsCDPK2, receptor-like protein,
OsNAC6 protein, and bHLH in the cardiac lobe were higher in Shuhe-WYL than in
Qingzha at 96 h after inoculation, but KH domain protein and RNA-binding protein
were not significantly different. The content of phenylalanine ammonia-lyase in
the cardiac lobe was higher in inoculated and non-inoculated Shuhe-WYL compared
to inoculated Qingzha at 15, 30, 45, and 60 days, and higher in inoculated Shuhe
WYL than in non-inoculated Shuhe-WYL at 15, 30, 45, and 60 days. The content of
phenylalanine ammonia-lyase in the cardiac lobe of inoculated Shuhe-WYL had no
significant difference between at 60 and at 45 days; and was higher at 60 and 45
days than at 30 and 15 days; and was higher at 30 days than at 15 days
(60~45?30?15 days). The C. mollissima Shuhe-WYL strain was resistant to D.
kuriphilus; high expression of OsCDPK2, receptor-like protein, OsNAC6 protein,
and bHLH and phenylalanine ammonia-lyase may explain the mechanism.
PMID- 26436387
TI - A new method of QTL identification for undersaturated maps.
AB - In many species, low levels of polymorphism prevent the assembly of linkage maps
that are used to identify genetic markers related to the expression of
quantitative trait loci (QTLs). This study compared two methods of locating QTLs
in association studies that do not require a previous estimation of linkage maps.
Method I (MI) was a Bayesian multiple marker regression and Method II (MII)
combined multiple QTL mapping and "moving away from markers". In this method,
markers are not directly regressed to the phenotype, but are used as pivots to
search for QTLs along the genome. To compare methods, we simulated 300
individuals from an F2 progeny with two levels of marker loss (20 and 80%). A
total of 165 markers and seven QTLs were spread along 11 chromosomes (roughly
emulating the genetic structure of the common bean, Phaseolus vulgaris). A real
data example with 186 progenies of a F2:4 generation of the species was analyzed
using 59 markers (17 simple sequence repeats, 31 amplified fragment length
polymorphisms, and 11 sequence-related amplified polymorphisms). MII was more
precise than MI for both levels of marker loss. For real data, MII detected 17
candidate positions for QTLs, whereas MI did not detect any. MII is a powerful
method that requires further studies with actual data and other designs such as
crossover, and genome-wide studies.
PMID- 26436388
TI - Establishment and rapid detection of a heterozygous missense mutation in the
CACNA1F gene by ARMS technique with double-base mismatched primers.
AB - Retinitis pigmentosa (RP) is a retinal degenerative disorder that often causes
complete blindness. Mutations of more than 50 genes have been identified as
associated with RP, including the CACNA1F gene. In a recent study, by employing
next-generation sequencing, we identified a novel mutation in the CACNA1F gene.
In this study, we used the amplification refractory mutation system (ARMS) and
identified a single nucleotide change c.1555C>T in exon 13 of the CACNA1F gene,
leading to the substitution of arginine by tryptophan (p.R519W) in a Chinese
individual affected by RP. This study actually confirms this novel mutation, and
establishes the ARMS technique for the detection of mutations in RP.
PMID- 26436389
TI - Correlation between polymorphisms in the IL-17A and IL-17F genes and development
of coronary artery disease.
AB - A case-control study was conducted to investigate the association between genetic
variants of IL-17A rs2275913 and IL-17F rs763780 and the development of coronary
artery disease (CAD) in a Chinese population. A total of 306 individuals with CAD
and 306 unaffected individuals were enrolled from the Zhengzhou People's Hospital
between May 2012 and May 2014. The IL-17A rs2275913 and IL-17F rs763780 genes
were genotyped by polymerase chain reaction combined with a restriction fragment
length polymorphism (PCR-RFLP). Logistic regression analysis revealed that
individuals with the AA genotype of rs2275913 were associated with increased risk
of CAD, compared to those with the GG genotype in a codominant model [adjusted
odds ratio (OR) = 1.96; 95% confidence interval (CI) = 1.10-3.53]. On the other
hand, the AA genotype of rs2275913 was correlated with moderately increased risk
of CAD compared to the GG + GA genotype (adjusted OR = 1.76; 95%CI = 1.02-3.07)
in a recessive model. However, no significant differences were observed between
polymorphisms at the IL-17F rs763780 locus and CAD risk, in codominant, dominant,
and recessive models. In conclusion, the results of our study suggested that the
IL-17A rs2275913 polymorphism may affect the development of CAD; however, no
significant association was observed between the IL-17F rs763780 polymorphism and
risk of CAD.
PMID- 26436390
TI - Effects of Pax3 and Pax7 expression on muscle mass in the Pekin duck (Anas
platyrhynchos domestica).
AB - This study aimed to investigate whether the differential expression of muscle
development-related genes is one of the reasons why muscle development differs
between Pekin, Jianchang, and Heiwu ducks, which are all domesticated duck breeds
(Anas platyrhynchos domestica) breeds. At 2 weeks of age, the RNA expression of
paired box 7 (Pax7), paired box 3 (Pax3), myogenic differentiation antigen
(MYOD), and myogenin (MYOG) genes were measured by quantitative polymerase chain
reaction, and Pax3 and Pax7 protein levels were detected by western blot assay.
Myofiber morphology was investigated using paraffin-embedded muscle sections. At
8 weeks of age, 30 ducks of each breed were slaughtered for meat quality
determination. The results revealed that Pax3 and Pax7 expression levels at both
the RNA and protein levels were high in the Pekin duck. In addition, MYOG
expression levels in the Jianchang duck were significantly higher than in the
other two duck breeds (P < 0.05). There were no significant differences in MYOD
expression levels between the breeds (P > 0.05). Myofiber diameter and cross
sectional area were the largest in the Pekin duck and the smallest in the Heiwu
duck. There were significant differences in slaughter data between these breeds,
and muscle content was greatest in the Pekin duck. The results indicate that the
muscle content of three different duck breeds is associated with the expression
of satellite-cell marker genes.
PMID- 26436391
TI - Protective effects of bifidobacteria on intestines in newborn rats with
necrotizing enterocolitis and its regulation on TLR2 and TLR4.
AB - We established a necrotizing enterocolitis (NEC) rat model and explored the role
of bifidobacteria in the intestines of the rats and its regulation on intestinal
Toll-like receptors (TLRs). Seventy-five newborn Sprague-Dawley rats were
randomly divided into 5 groups (15 rats/group): group A, artificial feeding group
(formula-fed); group B, NEC model (LPS + formula-fed); group C, bifidobacterium
(LPS + formula-fed + bifidobacterium microcapsules, intragastric administration);
group D, artificial feeding + bifidobacterium (formula-fed + bifidobacterium
microcapsules gavage); group E, rat breast-feeding group (rat breast-feeding).
After 3 days of feeding, rats were placed in incubators, fasted for 12 h, and
killed by decapitation. The ileocecal proximal segment ileum was fixed and
sliced; pathological examination was conducted, and TLR2, TLR4, and nuclear
factor-kB p65 protein expression in the intestinal tissue was detected by
immunohistochemistry. There was a statistically significant difference in
pathological scores between groups C and B (H = 21.789, P = 0.000), and the
former was lower than the latter. TLR2, TLR4, and nuclear factor-kB p65
expression in intestinal tissue was determined in groups A-E. There were
statistically significant differences between groups C and B (P = 0.001; P =
0.000; P = 0.000). Bifidobacteria had a protective effect on the intestines of
newborn rats with NEC, which showed reduced NEC and intestinal damage severity.
This observation may be related to the reduced levels of TLR2, TLR4, and nuclear
factor-kB P65 observed during the inflammatory response.
PMID- 26436392
TI - Potential of hypocotyl diameter in family selection aiming at plant architecture
improvement of common bean.
AB - Cultivars of common bean with more erect plant architecture and greater tolerance
to degree of lodging are required by producers. Thus, to evaluate the potential
of hypocotyl diameter (HD) in family selection for plant architecture improvement
of common bean, the HDs of 32 F2 plants were measured in 3 distinct populations,
and the characteristics related to plant architecture were analyzed in their
progenies. Ninety-six F2:3 families and 4 controls were evaluated in a randomized
block design, with 3 replications, analyzing plant architecture grade, HD, and
grain yield during the winter 2010 and drought 2011 seasons. We found that the
correlation between the HD of F2 plants and traits related to plant architecture
of F2:3 progenies were of low magnitude compared to the estimates for
correlations considering the parents, indicating a high environmental influence
on HD in bean plants. There was a predominance of additive genetic effects on the
determination of hypocotyl diameter, which showed higher precision and accuracy
compared to plant architecture grade. Thus, this characteristic can be used to
select progenies in plant architecture improvement of common beans; however,
selection must be based on the means of at least 39 plants in the plot, according
to the results of repeatability analysis.
PMID- 26436393
TI - Isolation and characterization of novel microsatellite markers from the sika deer
(Cervus nippon) genome.
AB - Microsatellite markers are widely and evenly distributed, and are highly
polymorphic. Rapid and convenient detection through automated analysis means that
microsatellite markers are widely used in the construction of plant and animal
genetic maps, in quantitative trait loci localization, marker-assisted selection,
identification of genetic relationships, and genetic diversity and phylogenetic
tree construction. However, few microsatellite markers remain to be isolated. We
used streptavidin magnetic beads to affinity-capture and construct a (CA)n
microsatellite DNA-enriched library from sika deer. We selected sequences
containing more than six repeats to design primers. Clear bands were selected,
which were amplified using non-specific primers following PCR amplification to
screen polymorphisms in a group of 65 unrelated sika deer. The positive clone
rate reached 82.9% by constructing the enriched library, and we then selected
positive clones for sequencing. There were 395 sequences with CA repeats, and the
CA repeat number was 4-105. We selected sequences containing more than six
repeats to design primers, of which 297 pairs were designed. We next selected
clear bands and used non-specific primers to amplify following PCR amplification.
In total, 245 pairs of primers were screened. We then selected 50 pairs of
primers to randomly screen for polymorphisms. We detected 47 polymorphic and 3
monomorphic loci in 65 unrelated sika deer. These newly isolated and
characterized microsatellite loci can be used to construct genetic maps and for
lineage testing in deer. In addition, they can be used for comparative genomics
between Cervidae species.
PMID- 26436394
TI - Effect of pulsed electromagnetic field therapy on the osteogenic and adipogenic
differentiation of bone marrow mesenchymal stem cells.
AB - We investigated the effects of pulsed electromagnetic fields (PEMFs) of 20 Hz/2
mT on the osteogenic and adipogenic differentiation of bone marrow stem cells
(BMSCs). Sprague Dawley rat BMSCs were isolated and cultured in vitro. The BMSCs
of the third passage were obtained and stimulated by PEMFs of 20 Hz/2 mT. The
alkaline phosphatase (ALP) activity was measured according to the ALP assay kit
manufacturer instructions, the BMSC osteogenic and adipogenic indicators were
detected by semi-quantitative reverse transcription polymerase chain reaction (RT
PCR), and oil red O staining was used to observe the adipose-induced adipogenic
differentiation of BMSCs. PEMFs of 20 Hz/2 mT significantly promoted the activity
of ALP in the BMSCs (P < 0.01) and mRNA expression of osteogenic proteins
(osteocalcin and osteopontin). The PEMFs inhibited the expression of adipogenic
transcription factors such as adipokines and adipocyte-binding protein-2, and the
adipogenic differentiation of BMSCs. PEMFs of 20 Hz/2 mT can promote osteogenic
differentiation and inhibit adipogenic differentiation in BMSCs.
PMID- 26436395
TI - Lack of clinical significance of the ImmuKnow(TM)-Cylex assay for the detection
of cellular immune function in patients with renal cell carcinoma.
AB - This study aimed to explore the clinical value of the CD4(+) T cell ATP levels in
patients with renal cell carcinoma through the application of the ImmuKnow(TM)
Cylex((r)) assay. We recruited 104 patients with renal cancer who had undergone
surgery at Fuzhou General Hospital from March 2009 to June 2012, and were
subsequently treated by dendritic cell and cytokine-induced killer cell bio
therapy or interferon-alpha therapy. The changes in CD4(+) T cell ATP levels were
detected at the perioperative period and at 10 days, 1 month, 3 months, and 1
year after the surgery using the ImmuKnow assay. In addition, the differences in
ATP levels in different therapy groups were compared and the prognosis conditions
were analyzed. Our results demonstrated that no significant difference in the ATP
levels occurred at different time points; furthermore, there were no obviously
different ATP levels between the different therapy groups, and the ATP levels
were found to have no clinical significance for the assessment of renal cancer
prognosis. Overall, this study suggested that CD4(+) T cell ATP levels as
detected by the ImmuKnow assay have no obvious clinical value in patients with
renal cancer.
PMID- 26436396
TI - Analysis of skin color change and related gene expression after crossing of
Dongxiang black chicken and ISA layer.
AB - This study evaluated the effects of the autosomal domi-nant Fm gene in
conjunction with the sex-linked Id gene on skin color and related gene
expression. Ten Dongxiang black cocks were selected to build ten families by
mating 60 individuals of ISA B-line layers. The skin color of the F1 generation
was observed at different time points. At 126 days, 36 chickens were slaughtered,
and gene expression of TYRP1, TYRP2, MC1R, and EDNRB in breast skin was assessed
by quantitative RT-PCR. The ratio of Dongxiang black chickens with white skin
chicks in the F1 generation to that of non-white was 3:7 (HoFF: HeFf). At 126
days, all F1 generation cocks showed white skin (115/115), while the percentages
of hens with black skin were 100% (HoFF, 27/27) and 53.75% (HeFf, 43/80). The
change in skin color peaked between 42 and 84 days. The offspring of HoFF
displayed significantly higher expres-sion of MC1R, compared with those of HeFf
(P < 0.05). The "L" value of hen's skin was significantly lower, and TYRP1 and
TYRP2 expres-sion was significantly higher (P < 0.05) than in cocks with the same
Fm/fm genotype. These findings indicate the presence of homozygous and
heterozygous Fm in Dongxiang black chickens, with the offspring of homozygous
birds showing a higher percentage of black skin percentage. The expression of the
four genes studied was correlated with skin color, with TYRP1 and TYRP2
representing the most suitable molecular markers.
PMID- 26436397
TI - Correlation between single nucleotide polymorphisms in hypoxia-related genes and
susceptibility to acute high-altitude pulmonary edema.
AB - This study aimed to explore the relationship between genetic changes and high
altitude pulmonary edema (HAPE) susceptibility, and to screen for the key single
nucleotide polymorphism (SNP) loci in the HAPE-susceptibility gene, by
investigating the SNPs occurring in hypoxia-related genes in HAPE-susceptible and
control (non-susceptible) populations. This research was conducted on Han
recruits, who travelled to the Lhasa plateau (altitude, 3658 m). Ten loci located
on ten genes extracted from the HAPE and healthy populations were amplified by
polymerase chain reaction, and subsequently sequenced. The investigated genes
included those coding for aldosterone synthase 2 (CYP11B2), angiotensin
converting enzyme (ACE), heat-shock protein 70 (HSP70), nuclear factor kappa B
(NF-kappaB), surfactant protein A2 (SP-A2), plasminogen activator inhibitor-1
(PAI-1), nitric oxide synthetase (NOS), vascular endothelial growth factor
(VEGF), prolyl hydroxylase (EGLN1), and zinc finger protein A20. The gene
distribution of each SNP loci and its correlation with HAPE was analyzed.
Statistical analyses of the genotype frequencies of the SNPs revealed significant
differences in the ACE (rs4309), EGLN1 (rs480902), SP-A2 (rs1965708), HSP70
(rs1008438), PAI-1 (rs1799889), and NOS (rs199983) expressions between the HAPE
and healthy control groups (P < 0.05); therefore, these SNP loci were believed to
indicate HAPE susceptibility. HAPE is correlated with multiple- SNP loci. A
correlation analysis between genetic polymorphism and HAPE susceptibility
revealed that 6 hypoxia-related genes were key sites accounting for HAPE. These
findings could help assess the risk of HAPE in populations expressing different
genotypes, in order to reduce the occurrence of HAPE.
PMID- 26436398
TI - Investigation of the value of miR-21 in the diagnosis of early stage HCC and its
prognosis: a meta-analysis.
AB - The diagnostic and prognostic value of miR-21 has been examined for
hepatocellular carcinoma (HCC), with inconsistent results. Present meta-analysis
summarized the diagnostic accuracy and the predictive role for survival of miR-21
in patients with HCC. All eligible studies were searched using PubMed, EMBASE,
and Chinese National Knowledge Infrastructure (CNKI) databases up to October
2014. For the diagnostic meta-analysis, the indices of miR-21 in the diagnosis of
HCC were pooled using bivariate random-effect approach models. For the prognostic
meta-analysis, data were synthesized with a random effect model, and the hazard
ratio (HR) or odd ratio (OR) with its 95% confidence interval (95%CI) was used as
the effect size estimate. Ten studies dealing with HCC were included. The overall
pooled results for sensitivity, specificity, and the area under the curve (AUC)
for the diagnostic meta-analysis (five studies) were 74.0 (95%CI = 61.0-85.0),
78.0 (95%CI = 67.0-86.0), and 0.83 (95%CI = 0.80-0.86), respectively. The
combined data for the prognostic meta-analysis (seven studies) suggested that miR
21 overexpression in HCC correlated with poor overall survival [HR = 1.19 (95%CI
= 0.44-1.94)], and higher miR-21 expression was associated with tumor, node,
metastases (TNM) stage [OR = 0.34 (95%CI = 0.13-0.91)]. We concluded that miR-21
might be complementary to alpha fetal protein in HCC diagnosis, and might serve
as an attractive estimator of HCC. We also demonstrated that miR-21
overexpression was associated with HCC TNM stage and with poor survival. As our
study was limited, additional prospective studies are needed to validate these
results.
PMID- 26436399
TI - Hypoxia-related gene expression in porcine skeletal muscle tissues at different
altitude.
AB - Hypoxia influences many physiological processes, such as respiration,
cardiovascular, neurophysiology, and digestion. Skeletal muscle is an important
motor organ, which relies on oxygen of oxidation; however, the study of hypoxia
in skeletal muscle is lacking. In order to understand the effect of hypoxia on
skeletal muscle, we determined the expression level of four hypoxia-related genes
(ADAM17, ARG2, MMP, and HIF1A) in two distinct skeletal muscle tissues from
Tibetan pigs that live at different altitudes (500 and 3650 m). Consistent with
the well-characterized role of four hypoxia-related genes in the adaptation to
high altitude, we found that, compared with the plain pigs, the plateau pigs had
higher mRNA abundances of the four genes and lower myofiber ratio in skeletal
muscle. The negative correlation between the myofiber ratio and mRNA abundance of
the four hypoxia-related genes highlights their critical roles in skeletal
muscle. These findings may be important for understanding skeletal muscle
adaptation to high altitude and hypoxia-related muscle diseases in humans.
PMID- 26436400
TI - Decreased expression of humanized Fat-1 in porcine fetal fibroblasts following
deletion of PGK-neomycin resistance.
AB - The neomycin-resistance (neo(r)) gene is widely used as a selectable marker in
eukaryotic expression vectors; however, its expression often affects that of
target genes. Cre recombinase recognizes LoxP sites, leading to site-specific
recombination and deletion of DNA and RNA between two LoxP sites. In the present
study, a humanized Fat-1 gene (hFat-1) was generated by DNA Works and used to
construct a pC-PGK-neo(r)-hfat-1 expression vector, in which PGK-neo(r) was
flanked by two LoxP sites. The pC-PGK-neo(r)-hfat-1 plasmids were transfected
into porcine fetal fibroblasts using liposomes, and three transgenic cell lines
were obtained by culturing with 400 MUg/mL G418 for 7 days. Next, these cell
lines were transfected with a Cre recombinase expression plasmid, which contains
a puromycin resistance gene, in order to delete neo(r), which was integrated into
the genome. hFat-1-neo(r) negative cells were obtained following puromycin
selection. Real-time quantitative polymerase chain reaction data indicated that
neomycin-resistant cells had higher hFat-1 expression than neomycin-sensitive
cells. High performance gas chromatography data suggested that the n-6/n-3 ratio
was significantly lower in transfected cells than in wild-type cells. The n-6/n-3
ratio in Cre-treated hFat-1-transfected cells was higher than that in untreated
cells, suggesting that deletion of PGK-neo(r) decreased hFat-1 expression.
PMID- 26436401
TI - Isolation and characterization of yeasts capable of efficient utilization of
hemicellulosic hydrolyzate as the carbon source.
AB - Few yeasts have shown the potential to efficiently utilize hemicellulosic
hydrolyzate as the carbon source. In this study, microorganisms isolated from the
Manaus region in Amazonas, Brazil, were characterized based on their utilization
of the pentoses, xylose, and arabinose. The yeasts that showed a potential to
assimilate these sugars were selected for the better utilization of
lignocellulosic biomass. Two hundred and thirty seven colonies of unicellular
microorganisms grown on hemicellulosic hydrolyzate, xylose, arabinose, and yeast
nitrogen base selective medium were analyzed. Of these, 231 colonies were
subjected to sugar assimilation tests. One hundred and twenty five of these were
shown to utilize hydrolyzed hemicellulose, xylose, or arabinose as the carbon
source for growth. The colonies that showed the best growth (N = 57) were
selected, and their internal transcribed spacer-5.8S rDNA was sequenced. The
sequenced strains formed four distinct groups in the phylogenetic tree, and
showed a high percentage of similarity with Meyerozyma caribbica, Meyerozyma
guilliermondii, Trichosporon mycotoxinivorans, Trichosporon loubieri, Pichia
kudriavzevii, Candida lignohabitans, and Candida ethanolica. The discovery of
these xylose-fermenting yeasts could attract widespread interest, as these can be
used in the cost-effective production of liquid fuel from lignocellulosic
materials.
PMID- 26436402
TI - Genetic diversity of wild soybean populations in Dongying, China, by simple
sequence repeat analysis.
AB - Annual wild soybean (Glycine soja Sieb. et Zucc.), the ancestor of cultivated
soybean (G. max), is believed to be a potential gene source for further
improvement of soybean to cope with environmental stress. In this study, 10
simple sequence repeat (SSR) markers were used to evaluate the genetic diversity
and population genetic structure in five wild soybean populations using 195
accessions collected from Dongying, China. Ten SSR markers yielded 90 bands, with
an average of nine bands per marker. The percentage of polymorphic loci (P) was
97.78%, the distribution of expected heterozygosity (HE) was 0.1994-0.4460 with
an average of 0.3262, and the distribution from Shannon's information index (I)
was 0.3595-0.6506 with an average of 0.5386. The results showed that wild soybean
had a high degree of genetic diversity at the species level. Nei's
differentiation coefficient (FST) was 0.1533, and gene flow (Nm) was 1.3805,
which indicated that genetic variation mainly existed within populations and that
there was a certain level of gene exchange between populations. Some genetic
differentiation occurred among populations, although this was not significant.
Cluster analysis indicated that there was no significant correlation between the
genetic structure of wild soybean populations and their geographic distribution,
and the clustering results may be relatively consistent with the habitats of the
accessions. In the present study, the genetic diversity of wild soybeans showed a
broad genetic base and enables suggestions for the conservation of this plant to
be made.
PMID- 26436403
TI - Microvascular remodeling of nasal mucosa in allergic rhinitis induced by an
allergen in Sprague-Dawley rats.
AB - This study aimed to observe microvascular changes in the nasal mucosa of Sprague
Dawley (SD) rats with allergic rhinitis (AR) after persistent exposure to an
allergen with fluticasone propionate (FP) treatment. Ninety healthy SD rats were
randomly distributed into the control group (A, N = 30), the group with continued
exposure to an allergen (B, N = 30), and FP treatment group (C, N = 30). The
animals of the persistence group were subjected to persistent exposure to an
allergen after 7 weeks of modeling of ovalbumin (OVA) provocation in the nasal
mucosa for 16 weeks. At the 8th, 12th, and 16th week after OVA provocation, each
group was euthanized at each time point: the FP treatment after OVA provocation,
and animals of the control group were not stimulated with OVA and were sacrificed
at the same time point. The nasal mucosa of 5 animals from each group was
analyzed for the expression of vascular endothelial growth factor (VEGF), and
another 5 animals were used to make micro vascular corrosion casts for a scanning
electron microscope. The results demonstrate that FP has a strong inhibitory
effect on angiogenesis in AR. Inhalation of FP had an antiangiogenic effect
through inhibition of VEGF expression but does not completely reverse the
remodeling of the nasal mucosa in the short term nor does it have complete
control over the expression of VEGF mRNA.
PMID- 26436404
TI - Analysis of the association between polymorphisms in the vitamin D receptor (VDR)
gene and dental caries in a Chinese population.
AB - Environmental influences on the development and progression of dental caries are
well known; however, there is little evidence of a genetic component imparting
susceptibility to dental caries. The aim of this study was to investigate the
relationship between a single nucleotide polymorphism in the vitamin D receptor
TaqI locus and dental caries susceptibility in a Chinese population. This case
control study was conducted with a case group (264 patients with dental caries
from northwestern China) and a control group (219 individuals without dental
caries or systemic disease from the same area). DNA was extracted from the
peripheral venous blood of the study participants; the distribution of TaqI locus
genotypes and allele frequencies was determined via polymerase chain reaction
restriction fragment length polymorphism. The data obtained were statistically
analyzed using the Hardy-Weinberg equilibrium and Chi-square test. The frequency
of the Tt genotype in the case group (14.0%) was significantly higher than that
in the control group (4.3%), as determined using the genotype TT as the
reference. The risk of dental caries was increased 3.8-fold in individuals with
the heterozygous Tt genotype compared to that in the individuals with the TT
genotype. The proportion of the 't' allele in the case group (7.0%) and the
control group (2.1%) was observed to be significantly different [P = 0.0003; OR =
3.592, confidence interval 95% (1.790-7.208)]. Our results therefore suggested
that the allele 't' might be a genetic factor determining dental caries
susceptibility in individuals from the northwest of China.
PMID- 26436405
TI - Morphological analysis and muscle-associated gene expression during different
muscle growth phases of Megalobrama amblycephala.
AB - Skeletal muscle growth is regulated by both positive and negative factors, such
as myogenic regulatory factors (MRFs) and myostatin (MSTN), and involves both
hyperplasia and hypertrophy. In the present study, morphological changes during
muscle development in Megalobrama amblycephala were characterized and gene
expression levels were measured by quantitative real-time polymerase chain
reaction (qRT-PCR) analysis in juvenile [60, 90, 120, and 180 days post-hatching
(dph)] and adult fish. Our results show that during muscle development, the
frequency of muscle fibers with a diameter <20 MUm dramatically decreased in both
red and white muscles, with a concomitant increase in the frequency of >30 MUm
fibers in red muscle and >50 MUm fibers in white muscle. At 90-120 dph, the ratio
of hyperplastic to hypertrophic areas in red and white muscles increased, but
later decreased at 120-180 dph. The effect of hypertrophy was significantly
larger than hyperplasia during these phases. qRT-PCR indicated MRF and MSTN
(MSTNa and MSTNb) genes had similar expression patterns that peaked at 120 dph,
with the exception of MSTNa. This new information on the molecular regulation of
muscle growth and rapid growth phases will be of value to the cultivation of M.
amblycephala.
PMID- 26436406
TI - Genetic variability of genes involved in DNA repair influence treatment outcome
in osteosarcoma.
AB - We conducted a perspective study to investigate the role of ERCC1 (rs11615),
ERCC2 (rs13181 and rs1799793), ERCC4 (rs1800067), and ERCC5 (rs17655) in NER
pathway in the prognosis of osteosarcoma patients. In total, 146 osteosarcoma
patients were recruited between 2008 and 2013. ERCC1 rs11615, ERCC2 rs13181 and
rs1799793, ERCC4 rs1800067, and ERCC5 rs17655 gene polymorphisms were assessed by
polymerase chain reaction-restriction fragment length polymorphism assay. By
multivariate Cox proportional hazards models, we found that carriers of ERCC1
rs11615 TT genotype showed significantly favorable survival compared to wide-type
CC genotype, and the adjusted OR (95%CI) was 0.24 (0.08-0.96). Moreover, we found
that subjects with ERCC2 rs1799793 AA genotype were associated with decreased
hazards of death in multivariate analysis (HR = 0.22, 95%CI = 0.12-0.93). In
conclusion, our results suggest that ERCC1 rs11615 and ERCC2 rs1799793 may be
useful genetic prognostic markers for osteosarcoma in a Chinese population.
PMID- 26436407
TI - Function Clustering Self-Organization Maps (FCSOMs) for mining differentially
expressed genes in Drosophila and its correlation with the growth medium.
AB - The central task of this study was to mine the gene-to-medium relationship.
Adequate knowledge of this relationship could potentially improve the accuracy of
differentially expressed gene mining. One of the approaches to differentially
expressed gene mining uses conventional clustering algorithms to identify the
gene-to-medium relationship. Compared to conventional clustering algorithms, self
organization maps (SOMs) identify the nonlinear aspects of the gene-to-medium
relationships by mapping the input space into another higher dimensional feature
space. However, SOMs are not suitable for huge datasets consisting of millions of
samples. Therefore, a new computational model, the Function Clustering Self
Organization Maps (FCSOMs), was developed. FCSOMs take advantage of the theory of
granular computing as well as advanced statistical learning methodologies, and
are built specifically for each information granule (a function cluster of
genes), which are intelligently partitioned by the clustering algorithm provided
by the DAVID_6.7 software platform. However, only the gene functions, and not
their expression values, are considered in the fuzzy clustering algorithm of
DAVID. Compared to the clustering algorithm of DAVID, these experimental results
show a marked improvement in the accuracy of classification with the application
of FCSOMs. FCSOMs can handle huge datasets and their complex classification
problems, as each FCSOM (modeled for each function cluster) can be easily
parallelized.
PMID- 26436408
TI - Accuracy of enzyme-linked immunospot assay for diagnosis of pleural tuberculosis:
a meta-analysis.
AB - Current methods for diagnosing tuberculous pleurisy are poor. Some studies have
explored the diagnostic value of a pleural effusion enzyme-linked immunospot
(ELISPOT) assay, but its accuracy remains controversial. Therefore, we performed
a meta-analysis of the existing evidence on the ability of the ELISPOT assay to
diagnose tuberculous pleurisy. We systematically searched PubMed, Google Scholar,
and EMBASE databases for studies measuring the sensitivity, specificity, and
other measures of accuracy of the pleural effusion ELISPOT assay for diagnosis of
tuberculous pleurisy. A total of nine studies were identified and subjected to
meta-analysis, giving the following pooled values for diagnostic accuracy:
sensitivity, 0.93 [95% confidence intervals (95%CI) = 0.90 to 0.95]; specificity,
0.90 (95%CI = 0.86 to 0.93); positive likelihood ratio, 8.21 (95%CI = 4.00 to
16.84); negative likelihood ratio, 0.11 (95%CI = 0.06 to 0.19); diagnostic odds
ratio, 88.26 (95%CI = 33.81 to 230.43); and the area under the curve, 0.9599
(standard error of the mean, 0.0134). The available evidence suggests that
pleural effusion ELISPOT assay is sufficiently accurate to diagnose tuberculous
pleurisy as a stand-alone technique. In fact, it appears to be superior to assays
based on adenosine deaminase and gamma interferon for screening patients and
confirming the diagnosis of tuberculous pleurisy.
PMID- 26436409
TI - Weak Hydrogen Bonding Enables Hard, Strong, Tough, and Elastic Hydrogels.
AB - A new type of "rigid and tough" hydrogel with excellent elasticity is designed by
dense clustering of hydrogen bonds within a loose chemical network. The resultant
hydrogel exhibits a good combination of high modulus (28 MPa), toughness (9300 J
m(-3) ), extensibility (800%), and tensile stress (2 MPa). Furthermore, the gel
displays good fatigue-resistance and complete and extremely fast recovery of
shape and mechanical properties (3 min at 37 degrees C).
PMID- 26436410
TI - An Atmospheric Constraint on the NO2 Dependence of Daytime Near-Surface Nitrous
Acid (HONO).
AB - Recent observations suggest a large and unknown daytime source of nitrous acid
(HONO) to the atmosphere. Multiple mechanisms have been proposed, many of which
involve chemistry that reduces nitrogen dioxide (NO2) on some time scale. To
examine the NO2 dependence of the daytime HONO source, we compare weekday and
weekend measurements of NO2 and HONO in two U.S. cities. We find that daytime
HONO does not increase proportionally to increases in same-day NO2, i.e., the
local NO2 concentration at that time and several hours earlier. We discuss
various published HONO formation pathways in the context of this constraint.
PMID- 26436411
TI - Cronobacter sakazakii bacteremia in a heart transplant patient with polycystic
kidney disease.
AB - Infections with Cronobacter sakazakii are mainly described among neonates and
infants, with contaminated powdered infant formulas most often incriminated as
the cause. We describe here a case of C. sakazakii bacteremia secondary to a
suspected cyst infection in a heart-and-kidney transplant patient with polycystic
kidney disease.
PMID- 26436412
TI - Chronic lichen sclerosus successfully treated with intralesional adalimumab.
PMID- 26436413
TI - Acute Ischemic Stroke Therapy: The Way Forward.
PMID- 26436415
TI - Supraspinal Transient Receptor Potential Subfamily V Member 1 (TRPV1) in Pain and
Psychiatric Disorders.
AB - The transient receptor potential subfamily V member 1 (TRPV1) belongs to the
diverse transient receptor potential (TRP) family of cation channels. It was
first characterized in primary afferent fibres as a receptor for capsaicin.
Peripheral TRPV1 has a very well-described role in nociception. However, TRPV1 is
now recognized to have a broader distribution and function, with
supraspinal/brain TRPV1 known to modulate pain processing. Recently, studies
employing histological, genetic and pharmacological approaches have provided
evidence that supraspinal TRPV1 also modulates brain neurobiology and behaviours
related to anxiety, depression and schizophrenia. Key brain regions involved in
TRPV1-mediated modulation of pain and affect include the periaqueductal grey,
hippocampus and medial prefrontal cortex. Thus, TRPV1 in the brain is emerging as
an important molecular substrate which is dually implicated in both pain and
psychiatric disorders, and represents a novel therapeutic target for these
conditions and their comorbidity.
PMID- 26436414
TI - Root Effect Haemoglobins in Fish May Greatly Enhance General Oxygen Delivery
Relative to Other Vertebrates.
AB - The teleost fishes represent over half of all extant vertebrates; they occupy
nearly every body of water and in doing so, occupy a diverse array of
environmental conditions. We propose that their success is related to a unique
oxygen (O2) transport system involving their extremely pH-sensitive haemoglobin
(Hb). A reduction in pH reduces both Hb-O2 affinity (Bohr effect) and carrying
capacity (Root effect). This, combined with a large arterial-venous pH change
(DeltapHa-v) relative to other vertebrates, may greatly enhance tissue oxygen
delivery in teleosts (e.g., rainbow trout) during stress, beyond that in mammals
(e.g., human). We generated oxygen equilibrium curves (OECs) at five different
CO2 tensions for rainbow trout and determined that, when Hb-O2 saturation is 50%
or greater, the change in oxygen partial pressure (DeltaPO2) associated with
DeltapHa-v can exceed that of the mammalian Bohr effect by at least 3-fold, but
as much as 21-fold. Using known DeltapHa-v and assuming a constant arterial
venous PO2 difference (Pa-vO2), Root effect Hbs can enhance O2 release to the
tissues by 73.5% in trout; whereas, the Bohr effect alone is responsible for
enhancing O2 release by only 1.3% in humans. Disequilibrium states are likely
operational in teleosts in vivo, and therefore the DeltapHa-v, and thus
enhancement of O2 delivery, could be even larger. Modeling with known Pa-vO2 in
fish during exercise and hypoxia indicates that O2 release from the Hb and
therefore potentially tissue O2 delivery may double during exercise and triple
during some levels of hypoxia. These characteristics may be central to
performance of athletic fish species such as salmonids, but may indicate that
general tissue oxygen delivery may have been the incipient function of Root
effect Hbs in fish, a trait strongly associated with the adaptive radiation of
teleosts.
PMID- 26436417
TI - Correction: When Less Is More: Non-monotonic Spike Sequence Processing in
Neurons.
PMID- 26436416
TI - Effects of Very Low Dose Fast Neutrons on Cell Membrane And Secondary Protein
Structure in Rat Erythrocytes.
AB - The effects of ionizing radiation on biological cells have been reported in
several literatures. Most of them were mainly concerned with doses greater than
0.01 Gy and were also concerned with gamma rays. On the other hand, the studies
on very low dose fast neutrons (VLDFN) are rare. In this study, we have
investigated the effects of VLDFN on cell membrane and protein secondary
structure of rat erythrocytes. Twelve female Wistar rats were irradiated with
neutrons of total dose 0.009 Gy (241Am-Be, 0.2 mGy/h) and twelve others were used
as control. Blood samples were taken at the 0, 4th, 8th, and 12th days
postirradiation. Fourier transform infrared (FTIR) spectra of rat erythrocytes
were recorded. Second derivative and curve fitting were used to analysis FTIR
spectra. Hierarchical cluster analysis (HCA) was used to classify group spectra.
The second derivative and curve fitting of FTIR spectra revealed that the most
significant alterations in the cell membrane and protein secondary structure upon
neutron irradiation were detected after 4 days postirradiation. The increase in
membrane polarity, phospholipids chain length, packing, and unsaturation were
noticed from the corresponding measured FTIR area ratios. This may be due to the
membrane lipid peroxidation. The observed band shift in the CH2 stretching bands
toward the lower frequencies may be associated with the decrease in membrane
fluidity. The curve fitting of the amide I revealed an increase in the percentage
area of alpha-helix opposing a decrease in the beta-structure protein secondary
structure, which may be attributed to protein denaturation. The results provide
detailed insights into the VLDFN effects on erythrocytes. VLDFN can cause an
oxidative stress to the irradiated erythrocytes, which appears clearly after 4
days postirradiation.
PMID- 26436419
TI - Correction: Attenuation of High-Frequency (50-200 Hz) Thalamocortical EEG Rhythms
by Propofol in Rats Is More Pronounced for the Thalamus than for the Cortex.
PMID- 26436418
TI - Andrographolide Analogue Induces Apoptosis and Autophagy Mediated Cell Death in
U937 Cells by Inhibition of PI3K/Akt/mTOR Pathway.
AB - BACKGROUND: Current chemotherapeutic agents based on apoptosis induction are
lacking in desired efficacy. Therefore, there is continuous effort to bring about
new dimension in control and gradual eradication of cancer by means of ever
evolving therapeutic strategies. Various forms of PCD are being increasingly
implicated in anti-cancer therapy and the complex interplay among them is vital
for the ultimate fate of proliferating cells. We elaborated and illustrated the
underlying mechanism of the most potent Andrographolide analogue (AG-4) mediated
action that involved the induction of dual modes of cell death-apoptosis and
autophagy in human leukemic U937 cells. PRINCIPAL FINDINGS: AG-4 induced
cytotoxicity was associated with redox imbalance and apoptosis which involved
mitochondrial depolarisation, altered apoptotic protein expressions, activation
of the caspase cascade leading to cell cycle arrest. Incubation with caspase
inhibitor Z-VAD-fmk or Bax siRNA decreased cytotoxic efficacy of AG-4 emphasising
critical roles of caspase and Bax. In addition, AG-4 induced autophagy as evident
from LC3-II accumulation, increased Atg protein expressions and autophagosome
formation. Pre-treatment with 3-MA or Atg 5 siRNA suppressed the cytotoxic effect
of AG-4 implying the pro-death role of autophagy. Furthermore, incubation with Z
VAD-fmk or Bax siRNA subdued AG-4 induced autophagy and pre-treatment with 3-MA
or Atg 5 siRNA curbed AG-4 induced apoptosis-implying that apoptosis and
autophagy acted as partners in the context of AG-4 mediated action. AG-4 also
inhibited PI3K/Akt/mTOR pathway. Inhibition of mTOR or Akt augmented AG-4 induced
apoptosis and autophagy signifying its crucial role in its mechanism of action.
CONCLUSIONS: Thus, these findings prove the dual ability of AG-4 to induce
apoptosis and autophagy which provide a new perspective to it as a potential
molecule targeting PCD for future cancer therapeutics.
PMID- 26436420
TI - Mortality Prediction in Patients Undergoing Non-Invasive Ventilation in
Intermediate Care.
AB - BACKGROUND: Intermediate Care Units (ImCU) have become an alternative scenario to
perform Non-Invasive Ventilation (NIV). The limited number of prognostic studies
in this population support the need of mortality prediction evaluation in this
context. OBJECTIVE: The objective of this study is to analyze the performance of
Simplified Acute Physiology Score (SAPS) II and 3 in patients undergoing NIV in
an ImCU. Additionally, we searched for new variables that could be useful to
customize these scores, in order to improve mortality prediction. DESIGN: Cohort
study with prospectively collected data from all patients admitted to a single
center ImCU who received NIV. The SAPS II and 3 scores with their respective
predicted mortality rates were calculated. Discrimination and calibration were
evaluated by calculating the area under the receiver operating characteristic
curve (AUC) and with the Hosmer-Lemeshow goodness of fit test for the models,
respectively. Binary logistic regression was used to identify new variables to
customize the scores for mortality prediction in this setting. PATIENTS: The
study included 241 patients consecutively admitted to an ImCU staffed by
hospitalists from April 2006 to December 2013. KEY RESULTS: The observed in
hospital mortality was 32.4% resulting in a Standardized Mortality Ratio (SMR) of
1.35 for SAPS II and 0.68 for SAPS 3. Mortality discrimination based on the AUC
was 0.73 for SAPS II and 0.69 for SAPS 3. Customized models including
immunosuppression, chronic obstructive pulmonary disease (COPD), acute pulmonary
edema (APE), lactic acid, pCO2 and haemoglobin levels showed better
discrimination than old scores with similar calibration power. CONCLUSIONS: These
results suggest that SAPS II and 3 should be customized with additional patient
risk factors to improve mortality prediction in patients undergoing NIV in
intermediate care.
PMID- 26436421
TI - The Undecided Have the Key: Interaction-Driven Opinion Dynamics in a Three State
Model.
AB - The effects of interpersonal interactions on individual's agreements result in a
social aggregation process which is reflected in the formation of collective
states, as for instance, groups of individuals with a similar opinion about a
given issue. This field, which has been a longstanding concern of sociologists
and psychologists, has been extended into an area of experimental social
psychology, and even has attracted the attention of physicists and
mathematicians. In this article, we present a novel model of opinion formation in
which agents may either have a strict preference for a choice, or be undecided.
The opinion shift emerges, in a threshold process, as a consequence of a
cumulative persuasion for either one of the two opinions in repeated
interactions. There are two main ingredients which play key roles in determining
the steady states: the initial fraction of undecided agents and the change in
agents' persuasion after each interaction. As a function of these two parameters,
the model presents a wide range of solutions, among which there are consensus of
each opinion and bi-polarization. We found that a minimum fraction of undecided
agents is not crucial for reaching consensus only, but also to determine a
dominant opinion in a polarized situation. In order to gain a deeper
comprehension of the dynamics, we also present the theoretical framework of the
model. The master equations are of special interest for their nontrivial
properties and difficulties in being solved analytically.
PMID- 26436422
TI - Prey Preference and Life Table of Amblyseius orientalis on Bemisia tabaci and
Tetranychus cinnabarinus.
AB - Amblyseius orientalis (Ehara) (Acari: Phytoseiidae) is a native predatory mite
species in China. It used to be considered as a specialist predator of spider
mites. However, recent studies show it also preys on other small arthropod pests,
such as Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). Experiments were
conducted to investigate (1) prey preference of A. orientalis between Tetranychus
cinnabarinus (Boisd.) (Acari: Tetranychidae) and B. tabaci, and (2) development,
consumption and life table parameters of A. orientalis when reared on T.
cinnabarinus, B. tabaci or a mix of both prey species. When preying on different
stages of T. cinnabarinus, A. orientalis preferred protonymphs, whereas when
preying on different stages of B. tabaci, A. orientalis preferred eggs. When
these two most preferred stages were provided together (T. cinnabarinus
protonymphs and B. tabaci eggs), A. orientalis randomly selected its prey.
Amblyseius orientalis was able to complete its life cycle on B. tabaci eggs, T.
cinnabarinus protonymphs, or a mix of both prey. However, its developmental
duration was 53.9% and 30.0% longer when reared on B. tabaci eggs than on T.
cinnabarinus and a mix of both prey, respectively. In addition, it produced only
a few eggs and its intrinsic rate of increase was negative when reared on B.
tabaci eggs, which indicates that B. tabaci is not sufficient to maintain A.
orientalis population. The intrinsic rates of increase were 0.16 and 0.23 when A.
orientalis was fed on the prey mix and T. cinnabarinus, respectively. These
results suggest that although B. tabaci is a poor food resource for A. orientalis
in comparison to T. cinnabarinus, A. orientalis is able to sustain its population
on a mix of both prey. This predatory mite may thus be a potential biological
control agent of B. tabaci when this pest co-occurs with the alternative minor
pest T. cinnabarinus.
PMID- 26436425
TI - Effect of Stone-Wales defects on the thermal conductivity of graphene.
AB - The problem of phonon scattering by strain fields caused by Stone-Wales (SW)
defects in graphene is studied in the framework of the deformation potential
approach. An explicit form of the phonon mean free path due to phonon-SW
scattering is obtained within the Born approximation. The mean free path
demonstrates a specific q-dependence varying as q (-3) at low wavevectors and
taking a constant value at large q. The thermal conductivity of graphene
nanoribbons (GNRs) is calculated with the three-phonon umklapp, SW and rough edge
scatterings taken into account. A pronounced decrease of the thermal conductivity
due to SW defects is found at low temperatures whereas at room temperatures and
above the phonon-phonon umklapp scattering becomes dominant. A comparison with
the case of vacancy defects shows that they play more important role in the
reduction of the thermal conductivity in GNRs over a wide temperature range.
PMID- 26436424
TI - Weighted Score Tests Implementing Model-Averaging Schemes in Detection of Rare
Variants in Case-Control Studies.
AB - Multi-locus effect modeling is a powerful approach for detection of genes
influencing a complex disease. Especially for rare variants, we need to analyze
multiple variants together to achieve adequate power for detection. In this
paper, we propose several parsimonious branching model techniques to assess the
joint effect of a group of rare variants in a case-control study. These models
implement a data reduction strategy within a likelihood framework and use a
weighted score test to assess the statistical significance of the effect of the
group of variants on the disease. The primary advantage of the proposed approach
is that it performs model-averaging over a substantially smaller set of models
supported by the data and thus gains power to detect multi-locus effects. We
illustrate these proposed approaches on simulated and real data and study their
performance compared to several existing rare variant detection approaches. The
primary goal of this paper is to assess if there is any gain in power to detect
association by averaging over a number of models instead of selecting the best
model. Extensive simulations and real data application demonstrate the advantage
the proposed approach in presence of causal variants with opposite directional
effects along with a moderate number of null variants in linkage disequilibrium.
PMID- 26436423
TI - A Retrospective Study on Genetic Heterogeneity within Treponema Strains:
Subpopulations Are Genetically Distinct in a Limited Number of Positions.
AB - BACKGROUND: Pathogenic uncultivable treponemes comprise human and animal
pathogens including agents of syphilis, yaws, bejel, pinta, and venereal
spirochetosis in rabbits and hares. A set of 10 treponemal genome sequences
including those of 4 Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL
1, Mexico A, SS14), 4 T. p. ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa
D, Fribourg-Blanc), 1 T. p. ssp. endemicum (TEN) strain (Bosnia A) and one strain
(Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPLC) were
examined with respect to the presence of nucleotide intrastrain heterogeneous
sites. METHODOLOGY/PRINCIPAL FINDINGS: The number of identified intrastrain
heterogeneous sites in individual genomes ranged between 0 and 7. Altogether, 23
intrastrain heterogeneous sites (in 17 genes) were found in 5 out of 10
investigated treponemal genomes including TPA strains Nichols (n = 5), DAL-1 (n =
4), and SS14 (n = 7), TPE strain Samoa D (n = 1), and TEN strain Bosnia A (n =
5). Although only one heterogeneous site was identified among 4 tested TPE
strains, 16 such sites were identified among 4 TPA strains. Heterogeneous sites
were mostly strain-specific and were identified in four tpr genes (tprC, GI, I,
K), in genes involved in bacterial motility and chemotaxis (fliI, cheC-fliY), in
genes involved in cell structure (murC), translation (prfA), general and DNA
metabolism (putative SAM dependent methyltransferase, topA), and in seven
hypothetical genes. CONCLUSIONS/SIGNIFICANCE: Heterogeneous sites likely
represent both the selection of adaptive changes during infection of the host as
well as an ongoing diversifying evolutionary process.
PMID- 26436426
TI - The hows and whys of face processing: Level of construal influences the holistic
processing of human faces.
AB - Face recognition and identification are optimized by holistic processing. Various
visual-spatial manipulations appear to have transfer effects on holistic face
processing. The present experiment tests the effects of a semantic manipulation-
of construal level--on holistic processing as measured by composite congruency
effects. Participants completed two blocks of trials. The first served as a
baseline, whereas the second included a manipulation of construal level. High
level construal resulted in stronger congruency effects, indicative of greater
holistic processing (relative to baseline and to low-level construal). These
results have implications for conceptualizations of both construal level and
holistic processing.
PMID- 26436427
TI - Any effects of social orientation priming on object-location memory are smaller
than initially reported.
AB - It has previously been reported that priming a collectivistic social orientation
(compared with an individualistic one) boosts object-location memory (Kuhnen &
Oyserman, 2002; Oyserman, Sorensen, Reber, & Chen, 2009). We conducted 4
experiments to replicate this reported effect, using the same methods as in those
initial reports. In Experiment 1 (n = 145), we found a hint of a priming effect
on object-location memory, but also an unanticipated interaction between priming
and gender. In Experiment 2 (n = 90), we included gender as a formal factor and
doubled the "dosage" of the priming, yet did not see any priming effects on
memory. In Experiment 3 (n = 101), we octupled the priming "dosage" and again saw
no significant effects on memory. Finally, in Experiment 4 (n = 102), we
performed an exact replication of the methods of the original reports and again
found no priming effects on memory. Any effects of this type of social
orientation priming on object-location memory appear to be smaller and/or less
robust than initially thought.
PMID- 26436428
TI - The role of action readiness in motivated behavior.
AB - According to many theories of motivation and decision making, the principal
driver of human behavior is the valuation of actions. Action value is computed as
the difference between stimulus value (the benefits and costs inherent in the
stimulus that is the target of the action) and action costs (the effort required
to perform the action). In the present work, we propose that action costs are
crucially influenced by the readiness to perform a given action. We define action
readiness as the ease with which an action may be initiated given the preaction
launch state of the individual. An action that has been frequently or recently
performed or rehearsed has a high level of action readiness, whereas an action
that has not been frequently or recently performed or rehearsed has a low level
of action readiness. By our account, if action readiness levels are high for a
given action, decreased action costs may result in action even when the stimulus
value is relatively low. Conversely, if action readiness levels are low for a
given action, even action costs that appear negligible can dominate positive
stimulus values, resulting in seemingly puzzling instances of inaction. We
develop and test these ideas in 3 studies across 233 participants using an image
viewing decision context and a logistic prediction model.
PMID- 26436429
TI - On the Utility of Spinel Oxide Hosts for Magnesium-Ion Batteries.
AB - There is immense interest to develop Mg-ion batteries, but finding suitable
cathode materials has been a challenge. The spinel structure has many advantages
for ion insertion and has been successfully used in Li-ion batteries. We present
here findings on the attempts to extract Mg from MgMn2O4-based spinels with acid
(H2SO4) and with NO2BF4. The acid treatment was able to fully remove all Mg from
MgMn2O4 by following a mechanism involving the disproportionation of Mn(3+), and
the extraction rate decreased with increasing cation disorder. Samples with
additional Mg(2+) ions in the octahedral sites (e.g., Mg1.1Mn1.9O4 and
Mg1.5Mn1.5O4) also exhibit complete or near complete demagnesiation due to an
additional mechanism involving ion exchange of Mg(2+) by H(+), but no Mg could be
extracted from MgMnAlO4 due to the disruption of Mn-Mn interaction/contact across
shared octahedral edges. In contrast, no Mg could be extracted with the oxidizing
agent NO2BF4 from MgMn2O4 or Mg1.5Mn1.5O4 as the electrostatic repulsion between
the divalent Mg(2+) ions prevents Mg(2+) diffusion through the 16c octahedral
sites, unlike Li(+) diffusion, suggesting that spinels may not serve as potential
hosts for Mg-ion batteries. The ability to extract Mg with acid in contrast to
that with NO2BF4 is attributed to Mn dissolution from the lattice and the
consequent reduction in electrostatic repulsion. The findings could provide
insights toward the design of Mg hosts for Mg-ion batteries.
PMID- 26436430
TI - Aqueous-Processed Inorganic Thin-Film Solar Cells Based on CdSe(x)Te(1-x)
Nanocrystals: The Impact of Composition on Photovoltaic Performance.
AB - Aqueous processed nanocrystal (NC) solar cells are attractive due to their
environmental friendliness and cost effectiveness. Controlling the bandgap of
absorbing layers is critical for achieving high efficiency for single and
multijunction solar cells. Herein, we tune the bandgap of CdTe through the
incorporation of Se via aqueous process. The photovoltaic performance of aqueous
CdSexTe1-x NCs is systematically investigated, and the impacts of charge
generation, transport, and injection on device performance for different
compositions are deeply discussed. We discover that the performance degrades with
the increasing Se content from CdTe to CdSe. This is mainly ascribed to the lower
conduction band (CB) of CdSexTe1-x with higher Se content, which reduces the
driving force for electron injection into TiO2. Finally, the performance is
improved by mixing CdSexTe1-x NCs with conjugated polymer poly(p
phenylenevinylene) (PPV), and power conversion efficiency (PCE) of 3.35% is
achieved based on ternary NCs. This work may provide some information to further
optimize the aqueous-processed NC and hybrid solar cells.
PMID- 26436431
TI - Electrical behaviour of dendritic spines as revealed by voltage imaging.
AB - Thousands of dendritic spines on individual neurons process information and
mediate plasticity by generating electrical input signals using a sophisticated
assembly of transmitter receptors and voltage-sensitive ion channel molecules.
Our understanding, however, of the electrical behaviour of spines is limited
because it has not been possible to record input signals from these structures
with adequate sensitivity and spatiotemporal resolution. Current interpretation
of indirect data and speculations based on theoretical considerations are
inconclusive. Here we use an electrochromic voltage-sensitive dye which acts as a
transmembrane optical voltmeter with a linear scale to directly monitor
electrical signals from individual spines on thin basal dendrites. The results
show that synapses on these spines are not electrically isolated by the spine
neck to a significant extent. Electrically, they behave as if they are located
directly on dendrites.
PMID- 26436432
TI - Discovery of stable skyrmionic state in ferroelectric nanocomposites.
AB - Non-coplanar swirling field textures, or skyrmions, are now widely recognized as
objects of both fundamental interest and technological relevance. So far,
skyrmions were amply investigated in magnets, where due to the presence of chiral
interactions, these topological objects were found to be intrinsically
stabilized. Ferroelectrics on the other hand, lacking such chiral interactions,
were somewhat left aside in this quest. Here we demonstrate, via the use of a
first-principles-based framework, that skyrmionic configuration of polarization
can be extrinsically stabilized in ferroelectric nanocomposites. The interplay
between the considered confined geometry and the dipolar interaction underlying
the ferroelectric phase instability induces skyrmionic configurations. The
topological structure of the obtained electrical skyrmion can be mapped onto the
topology of domain-wall junctions. Furthermore, the stabilized electrical
skyrmion can be as small as a few nanometers, thus revealing prospective skyrmion
based applications of ferroelectric nanocomposites.
PMID- 26436433
TI - Immediate Effects of Traditional Thai Massage on Psychological Stress as
Indicated by Salivary Alpha-Amylase Levels in Healthy Persons.
AB - BACKGROUND Stress can cause psychological and physiological changes. Many studies
revealed that massage can decrease stress. However, traditional Thai massage has
not been well researched in this regard. The purpose of this study was to
investigate the immediate effects of traditional Thai massage (TTM) on salivary
alpha-amylase levels (sAA), heart rate variability (HRV), autonomic nervous
system (ANS) function, and plasma renin activity (PRA). MATERIAL AND METHODS
Twenty-nine healthy participants were randomly allocated into either a
traditional Thai massage (TTM) group or Control (C) group, after which they were
switched to the other group with a 2-week wash-out period. Each of them was given
a 10-minute mental arithmetic test to induce psychological stress before a 1-hour
session of TTM or rest. RESULTS Within-groups comparison revealed that sAA was
significantly decreased (p<0.05) in the TTM group but not in the C group. HRV and
ANS function were significantly increased (p<0.05) and PRA was significantly
decreased (p<0.05) in both groups. However, low frequency per high frequency
ratio (LF/HF ratio) and ANS balance status were not changed. Only sAA was found
to be significantly different between groups (p<0.05). CONCLUSIONS We conclude
that both TTM and rest can reduce psychological stress, as indicated by decreased
sAA levels, increased parasympathetic activity, decreased sympathetic activity,
and decreased PRA. However, TTM may have a modest effect on stress reduction as
indicated by a reduced sAA.
PMID- 26436434
TI - Ferromagnetic Bare Metal Stent for Endothelial Cell Capture and Retention.
AB - Rapid endothelialization of cardiovascular stents is needed to reduce stent
thrombosis and to avoid anti-platelet therapy which can reduce bleeding risk. The
feasibility of using magnetic forces to capture and retain endothelial outgrowth
cells (EOC) labeled with super paramagnetic iron oxide nanoparticles (SPION) has
been shown previously. But this technique requires the development of a
mechanically functional stent from a magnetic and biocompatible material followed
by in-vitro and in-vivo testing to prove rapid endothelialization. We developed a
weakly ferromagnetic stent from 2205 duplex stainless steel using computer aided
design (CAD) and its design was further refined using finite element analysis
(FEA). The final design of the stent exhibited a principal strain below the
fracture limit of the material during mechanical crimping and expansion. One
hundred stents were manufactured and a subset of them was used for mechanical
testing, retained magnetic field measurements, in-vitro cell capture studies, and
in-vivo implantation studies. Ten stents were tested for deployment to verify if
they sustained crimping and expansion cycle without failure. Another 10 stents
were magnetized using a strong neodymium magnet and their retained magnetic field
was measured. The stents showed that the retained magnetism was sufficient to
capture SPION-labeled EOC in our in-vitro studies. SPION-labeled EOC capture and
retention was verified in large animal models by implanting 1 magnetized stent
and 1 non-magnetized control stent in each of 4 pigs. The stented arteries were
explanted after 7 days and analyzed histologically. The weakly magnetic stents
developed in this study were capable of attracting and retaining SPION-labeled
endothelial cells which can promote rapid healing.
PMID- 26436435
TI - Microperfusion Technique to Investigate Regulation of Microvessel Permeability in
Rat Mesentery.
AB - Experiments to measure the permeability properties of individually perfused
microvessels provide a bridge between investigation of molecular and cellular
mechanisms regulating vascular permeability in cultured endothelial cell
monolayers and the functional exchange properties of whole microvascular beds. A
method to cannulate and perfuse venular microvessels of rat mesentery and measure
the hydraulic conductivity of the microvessel wall is described. The main
equipment needed includes an intravital microscope with a large modified stage
that supports micromanipulators to position three different microtools: (1) a
beveled glass micropipette to cannulate and perfuse the microvessel; (2) a glass
micro-occluder to transiently block perfusion and enable measurement of
transvascular water flow movement at a measured hydrostatic pressure, and (3) a
blunt glass rod to stabilize the mesenteric tissue at the site of cannulation.
The modified Landis micro-occlusion technique uses red cells suspended in the
artificial perfusate as markers of transvascular fluid movement, and also enables
repeated measurements of these flows as experimental conditions are changed and
hydrostatic and colloid osmotic pressure difference across the microvessels are
carefully controlled. Measurements of hydraulic conductivity first using a
control perfusate, then after re-cannulation of the same microvessel with the
test perfusates enable paired comparisons of the microvessel response under these
well-controlled conditions. Attempts to extend the method to microvessels in the
mesentery of mice with genetic modifications expected to modify vascular
permeability were severely limited because of the absence of long straight and
unbranched microvessels in the mouse mesentery, but the recent availability of
the rats with similar genetic modifications using the CRISPR/Cas9 technology is
expected to open new areas of investigation where the methods described herein
can be applied.
PMID- 26436436
TI - Ethnic, Racial, and Socioeconomic Disparities in Retinoblastoma.
AB - IMPORTANCE: Most children with retinoblastoma in the United States are diagnosed
as having a large intraocular tumor burden that requires intensive ocular-salvage
treatment or enucleation. OBJECTIVE: To investigate the effect of socioeconomic
status, race, and ethnicity on the extent of disease and the outcomes of
retinoblastoma. DESIGN, SETTING, AND PARTICIPANTS: A population-based review of
18 Surveillance, Epidemiology, and End Results (SEER) registries. From January 1,
2000, through December 31, 2010, 830 cases of retinoblastoma were recorded for
children aged 0 to 9 years. Data were collected and analyzed from January 1,
2000, through December 31, 2010, with the last follow-up on December 31, 2010.
EXPOSURES: County-based socioeconomic variables analyzed included poverty level,
educational attainment, language isolation, crowding, unemployment, and
percentage of immigrants. MAIN OUTCOMES AND MEASURES: Extent of disease, ocular
outcome, and children's survival. RESULTS: Of the 830 individuals included,
Hispanic children had a higher percentage of extraocular disease (86 of 261
[33.0%] vs. 102 of 510 non-Hispanic children [20.0%]; odds ratio [OR], 1.97 [95%
CI, 1.38-2.79]). The percentage of extraocular cases was also higher in counties
with the following low socioeconomic status indicators: higher vs. lower poverty
status (115 of 413 [27.8%] vs. 73 of 358 [20.4%]; OR, 1.51; 95% CI, 1.06-2.14);
lower vs. higher educational attainment (115 of 400 [28.7%] vs. 73 of 371
[19.7%]; OR, 1.65; 95% CI, 1.16-2.34); higher vs. lower levels of crowding (124
of 398 [31.2%] vs. 64 of 373 [17.2%]; OR, 2.18; 95% CI, 1.53-3.13); higher vs.
lower unemployment (119 of 411 [28.9%] vs. 69 of 360 [19.2%]; OR, 1.72; 95% CI,
1.21-2.45); higher vs. lower language isolation (117 of 388 [30.2%] vs. 71 of 383
[18.5%]; OR, 1.89; 95% CI, 1.34-2.70); and higher vs. lower percentage of
immigrants (109 of 386 [28.2%] vs. 79 of 385 [20.5%]; OR, 1.52; 95% CI, 1.08
2.16). Higher rates of enucleation were associated with low educational
attainment (265 of 401 [66.1%] vs 309 of 421 [73.4%]; OR, 1.42; 95% CI, 1.04
1.93), a higher level of crowding (316 of 416 [76.0%] vs. 258 of 406 [63.5%]; OR,
1.81; 95% CI, 1.32-2.48), and Hispanic origin (202 of 271 [74.5%]; OR, 1.41; 95%
CI, 1.01-1.98). Relative survival at 5 years was lower among black compared with
non-Hispanic white children (92.7% vs. 99.2%; P < .001). CONCLUSIONS AND
RELEVANCE: Significant disparities exist in the care and outcomes of children
with retinoblastoma. A low socioeconomic status negatively affects disease extent
and ocular outcomes, presumably by limiting access to primary and cancer-directed
care. Hispanic children in particular have more advanced disease and higher rates
of enucleation.
PMID- 26436438
TI - Selectivity of Terahertz Gas-Phase Spectroscopy.
AB - Analytical potential of terahertz (THz) spectroscopy is assessed by comparing
selectivity for a set of eight environmentally important gases over THz and
infrared (IR) optical frequencies. Selectivity coefficients are determined over
selected spectral regions for acetaldehyde, acetonitrile, ethanol, water,
methanol, ammonia, propionaldehyde, and propionitrile. These selectivity
coefficients quantify the magnitude of the net analyte signal for each test
compound relative to the other seven. In addition to the THz spectral range (2
125 cm(-1)), selectivity coefficients are determined for the following IR regions
600-1300, 1300-2000, 2600-3100, 3100-4000, and 4000-6500 cm(-1). Highest
selectivity is afforded over the THz frequencies for six of the eight test
compounds and THz selectivity coefficients for the other two gases (water and
acetonitrile) are acceptable for environmental measurements.
PMID- 26436437
TI - Letter to the Editor.
PMID- 26436439
TI - Enhanced stability of black phosphorus field-effect transistors with SiO2
passivation.
AB - Few-layer black phosphorus (BP) has attracted much attention due to its high
mobility and suitable band gap for potential applic5ations in optoelectronics and
flexible devices. However, its instability under ambient conditions limits its
practical applications. Our investigations indicate that by passivation of the
mechanically exfoliated BP flakes with a SiO2 layer, the fabricated BP field
effect transistors (FETs) exhibit greatly enhanced environmental stability.
Compared to the unpassivated BP devices, which show a fast drop of on/off current
ratio by a factor of 10 after one week of ambient exposure, the SiO2-passivated
BP devices display a high retained on/off current ratio of over 600 after one
week of exposure, just a little lower than the initial value of 810. Our
investigations provide an effective route to passivate the few-layer BPs for
enhancement of their environmental stability.
PMID- 26436440
TI - How and why do interviewers try to make impressions on applicants? A qualitative
study.
AB - To remain viable in today's highly competitive business environments, it is
crucial for organizations to attract and retain top candidates. Hence,
interviewers have the goal not only of identifying promising applicants but also
of representing their organization. Although it has been proposed that
interviewers' deliberate signaling behaviors are a key factor for attracting
applicants and thus for ensuring organizations' success, no conceptual model
about impression management (IM) exists from the viewpoint of the interviewer as
separate from the applicant. To develop such a conceptual model on how and why
interviewers use IM, our qualitative study elaborates signaling theory in the
interview context by identifying the broad range of impressions that interviewers
intend to create on applicants, what kinds of signals interviewers deliberately
use to create their intended impressions, and what outcomes they pursue.
Following a grounded theory approach, multiple raters analyzed in-depth
interviews with interviewers and applicants. We also observed actual employment
interviews and analyzed memos and image brochures to generate a conceptual model
of interviewer IM. Results showed that the spectrum of interviewers' IM
intentions goes well beyond what has been proposed in past research. Furthermore,
interviewers apply a broad range of IM behaviors, including verbal and nonverbal
as well as paraverbal, artifactual, and administrative behaviors. An extensive
taxonomy of interviewer IM intentions, behaviors, and intended outcomes is
developed, interrelationships between these elements are presented, and avenues
for future research are derived.
PMID- 26436441
TI - The long road to employment: Incivility experienced by job seekers.
AB - This study addresses how job seekers' experiences of rude and discourteous
treatment--incivility--can adversely affect self-regulatory processes underlying
job searching. Using the social-cognitive model (Zimmerman, 2000), we integrate
social-cognitive theory with the goal orientation literature to examine how job
search self-efficacy mediates the relationship between incivility and job search
behaviors and how individual differences in learning goal orientation and avoid
performance goal orientation moderate that process. We conducted 3 studies with
diverse methods and samples. Study 1 employed a mixed-method design to understand
the nature of incivility within the job search context and highlight the role of
attributions in linking incivility to subsequent job search motivation and
behavior. We tested our hypotheses in Study 2 and 3 employing time-lagged
research designs with unemployed job seekers and new labor market entrants.
Across both Study 2 and 3 we found evidence that the negative effect of
incivility on job search self-efficacy and subsequent job search behaviors are
stronger for individuals low, rather than high, in avoid-performance goal
orientation. Theoretical implications of our findings and practical
recommendations for how to address the influence of incivility on job seeking are
discussed.
PMID- 26436442
TI - Self-Assembled Smart Nanocarriers for Targeted Drug Delivery.
AB - Nanostructured drug-carrier systems promise numerous benefits for drug delivery.
They can be engineered to precisely control drug-release rates or to target
specific sites within the body with a specific amount of therapeutic agent.
However, to achieve the best therapeutic effects, the systems should be designed
for carrying the optimum amount of a drug to the desired target where it should
be released at the optimum rate for a specified time. Despite numerous attempts,
fulfilling all of these requirements in a synergistic way remains a huge
challenge. The trend in drug delivery is consequently directed toward integrated
multifunctional carrier systems, providing selective recognition in combination
with sustained or triggered release. Capsules as vesicular systems enable drugs
to be confined for controlled release. Furthermore, carriers modified with
recognition groups can enhance the capability of encapsulated drug efficacy.
Here, recent advances are reviewed regarding designing and preparing assembled
capsules with targeting ligands or size controllable for selective recognition in
drug delivery.
PMID- 26436444
TI - Metabolic and body composition changes in first year following traumatic
amputation.
AB - Body composition and metabolism may change considerably after traumatic
amputation because of muscle atrophy and an increase in adiposity. The purpose of
this study was to quantify changes in weight, body composition, and metabolic
rate during the first year following traumatic amputation in military
servicemembers. Servicemembers without amputation were included for comparison.
Participants were measured within the first 12 wk after amputation (baseline) and
at 6, 9, and 12 mo after amputation. Muscle mass, fat mass, weight, and metabolic
rate were measured at each time point. There was a significant increase in weight
and body mass index in the unilateral group between baseline and all follow-up
visits (p < 0.01). Over the 12 mo period, total fat mass and trunk fat mass
increased in both unilateral and bilateral groups; however, these changes were
not statistically significant over time. Muscle mass increased in both the
unilateral and bilateral group despite percent of lean mass decreasing. No
changes in resting metabolism or walking energy expenditure were observed in any
group. The results of this study conclude that weight significantly increased
because of an increase in both fat mass and muscle mass in the first year
following unilateral and bilateral amputation.
PMID- 26436445
TI - Wheat leaf lipids during heat stress: II. Lipids experiencing coordinated
metabolism are detected by analysis of lipid co-occurrence.
AB - Identifying lipids that experience coordinated metabolism during heat stress
would provide information regarding lipid dynamics under stress conditions and
assist in developing heat-tolerant wheat varieties. We hypothesized that co
occurring lipids, which are up-regulated or down-regulated together through time
during heat stress, represent groups that can be explained by coordinated
metabolism. Wheat plants (Triticum aestivum L.) were subjected to 12 days of high
day and/or night temperature stress, followed by a 4-day recovery period. Leaves
were sampled at four time points, and 165 lipids were measured by electrospray
ionization-tandem mass spectrometry. Correlation analysis of lipid levels in 160
leaf samples from each of two wheat genotypes revealed 13 groups of lipids.
Lipids within each group co-occurred through the high day and night temperature
stress treatments. The lipid groups can be broadly classified as groups
containing extraplastidic phospholipids, plastidic glycerolipids, oxidized
glycerolipids, triacylglycerols, acylated sterol glycosides and sterol
glycosides. Current knowledge of lipid metabolism suggests that the lipids in
each group co-occur because they are regulated by the same enzyme(s). The results
suggest that increases in activities of desaturating, oxidizing, glycosylating
and acylating enzymes lead to simultaneous changes in levels of multiple lipid
species during high day and night temperature stress in wheat.
PMID- 26436446
TI - Multiple breath washout cannot be used for tidal breath parameter analysis in
infants.
AB - BACKGROUND: Multiple breath washout (MBW) testing with SF6 gas mixture is
routinely used to assess ventilation distribution in infants. It is currently
unknown whether SF6 changes tidal breathing parameters during MBW in infants. We
investigated if SF6 does change tidal breathing parameters in infants and whether
a separate tidal breathing trace prior to MBW testing is necessary. METHODS:
Tidal breathing during MBW was compared to standard tidal breathing in room air
in healthy infants (n = 38), preterm infants (n = 41), and infants with cystic
fibrosis (n = 41). Outcomes included inspiratory and expiratory times (TI and TE
), time to peak tidal inspiratory and expiratory flow (tPTIF and tPTEF), tidal
volume (VT ), respiratory rate (f), and minute ventilation (VE ). RESULTS: Breath
times were all significantly increased for both healthy (TE : -0.0790 [-0.10566,
0.05217]; mean difference [95% confidence intervals]) and CF (-0.109 [-0.15235,
0.06607]) infants during the MBW wash-in (P < 0.001). Healthy infants and those
with CF showed decreased f during MBW wash-in (P < 0.001); however, no change in
VT, resulting in a decreased VE (0.154 (0.086, 0.222) and 0.128 (0.069, 0.186)
for healthy and CF infants, respectively, P < 0.001). Preterm infants experienced
a decreased VE during both wash-in (0.134 [0.061, 0.207]; P < 0.001) and wash-out
phases of MBW (P < 0.05). CONCLUSION: There are differences in tidal breathing
parameters during MBW testing with SF6 in infants. It is, therefore, important to
measure a separate tidal breathing trace in room air, prior to MBW testing to
ensure rigour of tidal breath indices derived from analysis.
PMID- 26436447
TI - Natural antioxidants for non-alcoholic fatty liver disease: molecular targets and
clinical perspectives.
AB - Non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty
liver disease (NAFLD), is emerging as a main health problem in industrialized
countries. Lifestyle modifications are effective in the treatment of NAFLD;
however, the long-term compliance is low. Therefore, several pharmacological
treatments have been proposed but none has shown significant efficacy or long
term safety. Natural polyphenols are a heterogeneous class of polyphenolic
compounds contained in vegetables, which are being proposed for the treatment of
different metabolic disorders. Although the beneficial effect of these compounds
has traditionally related to their antioxidant properties, they also exert
several beneficial effects on hepatic and extra-hepatic glucose and lipid
homeostasis. Furthermore, natural polyphenols exert antifibrogenic and
antitumoural effects in animal models, which appear relevant from a clinical
point of view because of the association of NASH with cirrhosis and
hepatocellular carcinoma. Several polyphenols, such anthocyanins, curcumin and
resveratrol and those present in coffee, tea, soy are available in the diet and
their consumption can be proposed as part of a healthy diet for the treatment of
NAFLD. Other phenolic compounds, such as silymarin, are commonly consumed
worldwide as nutraceuticals or food supplements. Natural antioxidants are
reported to have beneficial effects in preclinical models of NAFLD and in pilot
clinical trials, and thus need clinical evaluation. In this review, we summarize
the existing evidence regarding the potential role of natural antioxidants in the
treatment of NAFLD and examine possible future clinical applications.
PMID- 26436449
TI - Transferable ab Initio Dipole Moment for Water: Three Applications to Bulk Water.
AB - We recently reported a second-generation, ab initio dipole moment surface (DMS)
for water and applied it successfully to the IR spectrum of liquid water at 300
K. Here the transferability of this DMS is demonstrated in three applications.
One is the distribution of monomer dipole moments, considering two definitions,
and effective atomic charges of liquid water at 300 K and also for a model of ice
Ih at 0 K. The second one is a calculation of the dielectric constant of liquid
water at 280, 300, 320, 340, 360 K, and the third one is correcting the
intensities of the IR spectrum of liquid water at 300 K, obtained using the q
TIP4P/F potential, bringing them into much improved agreement with experiment.
For the purpose of obtaining statistical ensembles we use molecular dynamics
simulations with the TIP4P+E3B water model developed by Skinner and co-workers.
The average monomer dipole moments for 300 K water and 0 K ice Ih are 2.94 and
3.54 D, respectively, in good agreement with literature values. Effective monomer
charge distributions are derived from the monomer dipoles and give average values
of -1.02 e for O and 0.51 e for H in liquid water, which are also in agreement
with values reported from experiment. The calculated dielectric constant of
liquid water at the above five temperatures is compared to experiment and is
roughly 10-15% lower than experiment.
PMID- 26436450
TI - Synthesis of highly strained bicyclic[3.n.1]alkenes by a metal-catalyzed Conia
ene reaction.
AB - A high yielding metal-catalysed Conia-ene reaction of 2-acetylenic ketones for
the synthesis of bicyclo[3.n.1]alkenes has been developed. This simple and
efficient 6-endo-dig-cyclization protocol enables the synthesis of a wide variety
of bicyclic systems, present in many natural products.
PMID- 26436448
TI - Postdepletion Lymphocyte Reconstitution During Belatacept and Rapamycin Treatment
in Kidney Transplant Recipients.
AB - Belatacept is used to prevent allograft rejection but fails to do so in a sizable
minority of patients due to inadequate control of costimulation-resistant T
cells. In this study, we report control of costimulation-resistant rejection when
belatacept was combined with perioperative alemtuzumab-mediated lymphocyte
depletion and rapamycin. To assess the means by which the alemtuzumab, belatacept
and rapamycin (ABR) regimen controls belatacept-resistant rejection, we studied
20 ABR-treated patients and characterized peripheral lymphocyte phenotype and
functional responses to donor, third-party and viral antigens using flow
cytometry, intracellular cytokine staining and carboxyfluorescein succinimidyl
ester-based lymphocyte proliferation. Compared with conventional
immunosuppression in 10 patients, lymphocyte depletion evoked substantial
homeostatic lymphocyte activation balanced by regulatory T and B cell phenotypes.
The reconstituted T cell repertoire was enriched for CD28(+) naive cells, notably
diminished in belatacept-resistant CD28(-) memory subsets and depleted of
polyfunctional donor-specific T cells but able to respond to third-party and
latent herpes viruses. B cell responses were similarly favorable, without
alloantibody development and a reduction in memory subsets-changes not seen in
conventionally treated patients. The ABR regimen uniquely altered the immune
profile, producing a repertoire enriched for CD28(+) T cells, hyporesponsive to
donor alloantigen and competent in its protective immune capabilities. The
resulting repertoire was permissive for control of rejection with belatacept
monotherapy.
PMID- 26436451
TI - Projections from neocortex mediate top-down control of memory retrieval.
AB - Top-down prefrontal cortex inputs to the hippocampus have been hypothesized to be
important in memory consolidation, retrieval, and the pathophysiology of major
psychiatric diseases; however, no such direct projections have been identified
and functionally described. Here we report the discovery of a monosynaptic
prefrontal cortex (predominantly anterior cingulate) to hippocampus (CA3 to CA1
region) projection in mice, and find that optogenetic manipulation of this
projection (here termed AC-CA) is capable of eliciting contextual memory
retrieval. To explore the network mechanisms of this process, we developed and
applied tools to observe cellular-resolution neural activity in the hippocampus
while stimulating AC-CA projections during memory retrieval in mice behaving in
virtual-reality environments. Using this approach, we found that learning drives
the emergence of a sparse class of neurons in CA2/CA3 that are highly correlated
with the local network and that lead synchronous population activity events;
these neurons are then preferentially recruited by the AC-CA projection during
memory retrieval. These findings reveal a sparsely implemented memory retrieval
mechanism in the hippocampus that operates via direct top-down prefrontal input,
with implications for the patterning and storage of salient memory
representations.
PMID- 26436453
TI - A two-qubit logic gate in silicon.
AB - Quantum computation requires qubits that can be coupled in a scalable manner,
together with universal and high-fidelity one- and two-qubit logic gates. Many
physical realizations of qubits exist, including single photons, trapped ions,
superconducting circuits, single defects or atoms in diamond and silicon, and
semiconductor quantum dots, with single-qubit fidelities that exceed the
stringent thresholds required for fault-tolerant quantum computing. Despite this,
high-fidelity two-qubit gates in the solid state that can be manufactured using
standard lithographic techniques have so far been limited to superconducting
qubits, owing to the difficulties of coupling qubits and dephasing in
semiconductor systems. Here we present a two-qubit logic gate, which uses single
spins in isotopically enriched silicon and is realized by performing single- and
two-qubit operations in a quantum dot system using the exchange interaction, as
envisaged in the Loss-DiVincenzo proposal. We realize CNOT gates via controlled
phase operations combined with single-qubit operations. Direct gate-voltage
control provides single-qubit addressability, together with a switchable exchange
interaction that is used in the two-qubit controlled-phase gate. By independently
reading out both qubits, we measure clear anticorrelations in the two-spin
probabilities of the CNOT gate.
PMID- 26436452
TI - Cryo-electron microscopy structure of the Slo2.2 Na(+)-activated K(+) channel.
AB - Na(+)-activated K(+) channels are members of the Slo family of large conductance
K(+) channels that are widely expressed in the brain, where their opening
regulates neuronal excitability. These channels fulfil a number of biological
roles and have intriguing biophysical properties, including conductance levels
that are ten times those of most other K(+) channels and gating sensitivity to
intracellular Na(+). Here we present the structure of a complete Na(+)-activated
K(+) channel, chicken Slo2.2, in the Na(+)-free state, determined by cryo
electron microscopy at a nominal resolution of 4.5 angstroms. The channel is
composed of a large cytoplasmic gating ring, in which resides the Na(+)-binding
site and a transmembrane domain that closely resembles voltage-gated K(+)
channels. In the structure, the cytoplasmic domain adopts a closed conformation
and the ion conduction pore is also closed. The structure reveals features that
can explain the unusually high conductance of Slo channels and how contraction of
the cytoplasmic gating ring closes the pore.
PMID- 26436454
TI - Hedgehog actively maintains adult lung quiescence and regulates repair and
regeneration.
AB - Postnatal tissue quiescence is thought to be a default state in the absence of a
proliferative stimulus such as injury. Although previous studies have
demonstrated that certain embryonic developmental programs are reactivated
aberrantly in adult organs to drive repair and regeneration, it is not well
understood how quiescence is maintained in organs such as the lung, which
displays a remarkably low level of cellular turnover. Here we demonstrate that
quiescence in the adult lung is an actively maintained state and is regulated by
hedgehog signalling. Epithelial-specific deletion of sonic hedgehog (Shh) during
postnatal homeostasis in the murine lung results in a proliferative expansion of
the adjacent lung mesenchyme. Hedgehog signalling is initially downregulated
during the acute phase of epithelial injury as the mesenchyme proliferates in
response, but returns to baseline during injury resolution as quiescence is
restored. Activation of hedgehog during acute epithelial injury attenuates the
proliferative expansion of the lung mesenchyme, whereas inactivation of hedgehog
signalling prevents the restoration of quiescence during injury resolution.
Finally, we show that hedgehog also regulates epithelial quiescence and
regeneration in response to injury via a mesenchymal feedback mechanism. These
results demonstrate that epithelial-mesenchymal interactions coordinated by
hedgehog actively maintain postnatal tissue homeostasis, and deregulation of
hedgehog during injury leads to aberrant repair and regeneration in the lung.
PMID- 26436455
TI - Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound
Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.
AB - Compound muscle action potential (CMAP) and motor unit number estimation (MUNE)
are electrophysiological techniques that can be used to monitor the functional
status of a motor unit pool in vivo. These measures can provide insight into the
normal development and degeneration of the neuromuscular system. These measures
have clear translational potential because they are routinely applied in
diagnostic and clinical human studies. We present electrophysiological techniques
similar to those employed in humans to allow recordings of mouse sciatic nerve
function. The CMAP response represents the electrophysiological output from a
muscle or group of muscles following supramaximal stimulation of a peripheral
nerve. MUNE is an electrophysiological technique that is based on modifications
of the CMAP response. MUNE is a calculated value that represents the estimated
number of motor neurons or axons (motor control input) supplying the muscle or
group of muscles being tested. We present methods for recording CMAP responses
from the proximal leg muscles using surface recording electrodes following the
stimulation of the sciatic nerve in mice. An incremental MUNE technique is
described using submaximal stimuli to determine the average single motor unit
potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to
peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques
allow repeated measures in both neonatal and adult mice in such a manner that
facilitates rapid analysis and data collection while reducing the number of
animals required for experimental testing. Furthermore, these measures are
similar to those recorded in human studies allowing more direct comparisons.
PMID- 26436456
TI - Do cherished children age successfully? Longitudinal findings from the Veterans
Affairs Normative Aging Study.
AB - Although early adversity has been linked to worse mental and physical health in
adulthood, few studies have investigated the pathways through which positive and
negative dimensions of early experiences can jointly influence psychological well
being in later life. This study examined: (a) profiles of early experiences
across multiple domains, (b) the relations of these profiles to hedonic and
eudaimonic well-being in later life, and (c) whether midlife social support
mediated these relations. We first conducted latent class analysis of early
experiences using data from 1,076 men in the VA Normative Aging Study who
completed the Childhood Experiences Scale (age: M = 69, SD = 7). Analyses yielded
3 profiles of early experiences, labeled as cherished (strong support and some
losses), harshly disciplined (harsh parental discipline, low positive
reinforcement, and nonnormative stressors), and ordinary (few stressors and low
parental attention). Next, we applied structural equation modeling to data on a
subset of this sample assessed 7 years later on hedonic and eudaimonic well-being
(n = 496; age: M = 76, SD = 7). In general, the cherished group reported stronger
qualitative social support in midlife than the harshly disciplined and ordinary
groups, which in turn was related to greater hedonic (life satisfaction, positive
affect) and eudaimonic (competence, positive relations with others) well-being in
later life. The cherished group also reported higher autonomy than the ordinary
group, but this association was independent of midlife social support. Our
findings suggest that experiencing adversity in the context of a nurturing early
environment can promote successful aging through the maintenance of supportive
relationships in midlife.
PMID- 26436457
TI - Gene Positioning Effects on Expression in Eukaryotes.
AB - The packaging and organization of the genome within the eukaryotic interphase
nucleus directly influence how the genes are expressed. An underappreciated
aspect of genome structure is that it is highly dynamic and that the physical
positioning of a gene can impart control over its transcriptional status. In this
review, we assess the current knowledge of how gene positioning at different
levels of genome organization can directly influence gene expression during
interphase. The levels of organization discussed include chromatin looping,
topologically associated domains, chromosome territories, and nuclear
compartments. We discuss specific studies demonstrating that gene positioning is
a dynamic and highly regulated feature of the eukaryotic genome that allows for
the essential spatiotemporal regulation of genes.
PMID- 26436459
TI - Population Genomics for Understanding Adaptation in Wild Plant Species.
AB - Darwin's theory of evolution by natural selection is the foundation of modern
biology. However, it has proven remarkably difficult to demonstrate at the
genetic, genomic, and population level exactly how wild species adapt to their
natural environments. We discuss how one can use large sets of multiple genome
sequences from wild populations to understand adaptation, with an emphasis on the
small herbaceous plant Arabidopsis thaliana. We present motivation for such
studies; summarize progress in describing whole-genome, species-wide sequence
variation; and then discuss what insights have emerged from these resources,
either based on sequence information alone or in combination with phenotypic
data. We conclude with thoughts on opportunities with other plant species and the
impact of expected progress in sequencing technology and genome engineering for
studying adaptation in nature.
PMID- 26436460
TI - Chromosome-Membrane Interactions in Bacteria.
AB - Prokaryotes, by definition, do not segregate their genetic material from the
cytoplasm. Thus, there is no barrier preventing direct interactions between
chromosomal DNA and the plasma membrane. The possibility of such interactions in
bacteria was proposed long ago and supported by early electron microscopy and
cell fractionation studies. However, the identification and characterization of
chromosome-membrane interactions have been slow in coming. Recently, this subject
has seen more progress, driven by advances in imaging techniques and in the
exploration of diverse cellular processes. A number of loci have been identified
in specific bacteria that depend on interactions with the membrane for their
function. In addition, there is growing support for a general mechanism of DNA
membrane contacts based on transertion-concurrent transcription, translation, and
insertion of membrane proteins. This review summarizes the history and recent
results of chromosome-membrane associations and discusses the known and theorized
consequences of these interactions in the bacterial cell.
PMID- 26436458
TI - Nonsense-Mediated mRNA Decay: Degradation of Defective Transcripts Is Only Part
of the Story.
AB - Nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that
monitors cytoplasmic mRNA translation and targets mRNAs undergoing premature
translation termination for rapid degradation. From yeasts to humans, activation
of NMD requires the function of the three conserved Upf factors: Upf1, Upf2, and
Upf3. Here, we summarize the progress in our understanding of the molecular
mechanisms of NMD in several model systems and discuss recent experiments that
address the roles of Upf1, the principal regulator of NMD, in the initial
targeting and final degradation of NMD-susceptible mRNAs. We propose a unified
model for NMD in which the Upf factors provide several functions during premature
termination, including the stimulation of release factor activity and the
dissociation and recycling of ribosomal subunits. In this model, the ultimate
degradation of the mRNA is the last step in a complex premature termination
process.
PMID- 26436462
TI - ClC-3 chloride channel functions as a mechanically sensitive channel in
osteoblasts.
AB - Mechanical stimulation usually causes the volume changes of osteoblasts. Whether
these volume changes could be sensed by the ClC-3 chloride channel, a volume
sensitive ion channel, and further promote the osteodifferentiation in
osteoblasts has not been determined. In this study, we applied persistent static
compression on MC3T3-E1 cells to detect the expression changes of ClC-3,
osteogenic markers, as well as some molecules related with signaling transduction
pathway. We tested the key role of ClC-3 in transferring the mechanical signal to
osteoinduction by ClC-3 overexpressing and siRNA technique. We found that ClC-3
level was up-regulated by mechanical stimulation in MC3T3-E1 cells. Mechanical
force also up-regulated the mRNA level of osteogenic markers such as alkaline
phosphatase (Alp), bone sialoprotein (Bsp), and osteocalcin (Oc), which could be
blocked or strengthened by Clcn3 siRNA or overexpressing, and Alp expression was
more sensitive to the changes of ClC-3 level. We also found that runt-related
transcription factor 2 (Runx2), transforming growth factor beta 1 (TGF-beta1),
and Wnt pathway might be involved in ClC-3 mediated mechanical transduction in
osteoblasts. The data from the current study suggest that the ClC-3 chloride
channel acts as a mechanically sensitive channel to regulate osteodifferentiation
in osteoblasts.
PMID- 26436463
TI - The role of cardiorespiratory fitness on plasma lipid levels.
AB - Dyslipidemia is a treatable risk factor for cardiovascular disease.
Epidemiological studies have demonstrated the importance of treatment for
abnormalities in total cholesterol, LDL-cholesterol, HDL-cholesterol and
triglycerides. Aside from pharmacotherapy, exercise and cardio-respiratory
fitness have been shown to have beneficial effects on decreasing cardiovascular
disease risk. Even though previous data regarding the benefits of exercise on
plasma lipids have been somewhat conflicting, numerous studies have demonstrated
that exercise increases HDL-cholesterol and reduces the triglyceride levels.
Also, smaller, more atherogenic LDL particles seem to decrease with increases in
cardio-respiratory fitness and exercise, and favorable blood lipid profiles seem
to persist longer through the adult life span.
PMID- 26436464
TI - The Interactive Effects of Impulsivity and Negative Emotions on Adolescent
Nonsuicidal Self-injury: A Latent Growth Curve Analysis.
AB - This study employed latent growth curve analysis to evaluate the interactive
effects of two specific facets of impulsivity (i.e., negative urgency [NU] and
premeditation [PRE]) and negative emotions (NE) on the developmental trajectory
of nonsuicidal self-injury (NSSI) among 3,453 (57% females) Chinese community
adolescents. Participants completed questionnaires assessing NSSI, NU, PRE, and
NE (i.e., depression, anxiety, and stress) at three waves of time. The initial
levels of NE and NU significantly predicted the initial level of NSSI. Changes in
NE and NU significantly predicted change in NSSI. Moreover, the initial levels of
NU and PRE significantly moderated the relationship between the initial levels of
NE and NSSI, such that among individuals with higher NU or less PRE, the three NE
were associated with a higher level of NSSI. Additionally, among individuals with
a faster increase in NU, depression and anxiety were associated with a faster
increase in NSSI. These findings suggest that adolescents with trait impulsivity,
especially in the form of NU, are more vulnerable to the engagement in NSSI.
PMID- 26436461
TI - Eukaryotic Mismatch Repair in Relation to DNA Replication.
AB - Three processes act in series to accurately replicate the eukaryotic nuclear
genome. The major replicative DNA polymerases strongly prevent mismatch
formation, occasional mismatches that do form are proofread during replication,
and rare mismatches that escape proofreading are corrected by mismatch repair
(MMR). This review focuses on MMR in light of increasing knowledge about nuclear
DNA replication enzymology and the rate and specificity with which mismatches are
generated during leading- and lagging-strand replication. We consider differences
in MMR efficiency in relation to mismatch recognition, signaling to direct MMR to
the nascent strand, mismatch removal, and the timing of MMR. These studies are
refining our understanding of relationships between generating and repairing
replication errors to achieve accurate replication of both DNA strands of the
nuclear genome.
PMID- 26436465
TI - A Dual-Ion Battery Cathode via Oxidative Insertion of Anions in a Metal-Organic
Framework.
AB - A redox-active metal-organic framework, Fe2(dobpdc) (dobpdc(4-) = 4,4'
dioxidobiphenyl-3,3'-dicarboxylate), is shown to undergo a topotactic oxidative
insertion reaction with a variety of weakly coordinating anions, including BF4(-)
and PF6(-). The reaction results in just a minor lattice contraction, and a broad
intervalence charge-transfer band emerges, indicative of charge mobility.
Although both metal- and ligand-based oxidations can be accessed, only the former
were found to be fully reversible and, importantly, proceed stoichiometrically
under both chemical and electrochemical conditions. Electrochemical measurements
probing the effects of nanoconfinement on the insertion reaction revealed strong
anion size and solvent dependences. Significantly, the anion insertion behavior
of Fe2(dobpdc) enabled its use in the construction of a dual-ion battery
prototype incorporating a sodium anode. As a cathode, the material displays a
particularly high initial reduction potential and is further stable for at least
50 charge/discharge cycles, exhibiting a maximum specific energy of 316 Wh/kg.
PMID- 26436466
TI - Regulatory systemic effect of postsurgical polychromatic light (480-3400 nm)
irradiation of breast cancer patients on the proliferation of tumor and normal
cells in vitro.
AB - OBJECTIVE: The aim of this work was to study the effect of phototherapy (PT) with
percutaneous exposures to polychromatic visible and IR light (pVIS + pIR) on
breast cancer (BC) patients at the early postmastectomy period, on the growth
promoting (GP) properties of their blood serum, by evaluating its capability to
support proliferation of normal and tumor human cells in vitro. MATERIAL AND
METHODS: After mastectomy, one group of patients was treated daily for 1 week on
the sacral area with pVIS + pIR light (480-3400 nm, 40 mW/cm(2), 95%
polarization, 24 J/cm(2)). The second group used as a control was sham
irradiated. Blood serum samples collected before surgery, and 1 and 8 days after
surgery, were added (2.5%) into nutrition media for cells instead of 10% of fetal
calf serum. Cell targets were cultures of human fibroblasts (FBs), keratinocytes
(KCs), three lines of the human BC cells (BT-474, HBL-100, Hs 578T) and cells of
human epidermoid carcinoma (A-431). Cell number was evaluated by staining cell
nuclei with crystal violet and a spectrometric assay of the extracted dye.
RESULTS: The day after mastectomy there were no significant changes in the GP
activity of sera. After a 7-day PT course, an increase of this activity was
recorded for normal FBs and KCs by 18% and 24%, respectively, in comparison with
presurgical levels. GP activity of the same patients' sera for all tumor cells,
BT-474, HBL-100, Hs 578T and A-431, decreased by 32%, 17%, 11%, and 7%
respectively. As a result, enhancement of proliferation of KCs and FBs and
inhibition of proliferation of tumor cells was seen. CONCLUSIONS: The results
suggest an effect at the systemic level where pVIS + pIR light may stimulate
growth of human skin cells and simultaneously downregulate the proliferation of
tumor cells, including BC cells. This argues in favor of the oncological safety
of PT for BC patients postsurgically.
PMID- 26436467
TI - Gene Editing Versus Morphants.
PMID- 26436469
TI - Prevalence and spatial distribution of cattle herds infected with Theileria
orientalis in New Zealand between 2012 and 2013.
AB - AIM: To describe the prevalence and spatial distribution of cattle herds infected
with Ikeda and non-Ikeda types of Theileria orientalis in New Zealand between
November 2012 and June 2013. METHODS: Pooled serum samples collected historically
between November 2012 and June 2013 were obtained from cattle herds throughout
New Zealand. Each pooled sample consisted of approximately 20 individual cattle
samples from that herd, and was provided with details of the spatial location of
the herd (n=722). DNA from all samples was tested using two quantitative PCR
assays for the detection of T. orientalis (all types) and the Ikeda type. The
proportion of herds that were positive for T. orientalis and Ikeda type, or that
were positive for T. orientalis but negative for Ikeda type (non-Ikeda positive)
was determined for different regions of New Zealand. RESULTS: The highest
prevalence of herds infected with Ikeda type was detected in the Northland
(33/35; 94%) and Auckland and the Waikato (63/191; 33%) regions. Only 2/204 (1%)
herds were positive for the Ikeda type in the South Island. A high percentage of
herds that were positive for non-Ikeda types was detected in the Gisborne and
Hawkes Bay (23 (95%CI=13-37)%), Auckland and Waikato (22 (95%CI=16-29)%) and Bay
of Plenty (24 (95%CI=10-44)%) regions. CONCLUSIONS AND CLINICAL RELEVANCE: The
high prevalence of Ikeda type detected in cattle herds in the Northland, Auckland
and Waikato regions represents a risk to naive cattle being introduced into these
regions. There is also the potential for resident cattle herds in the Gisborne
and Hawkes Bay, Auckland, Waikato and Bay of Plenty regions to experience
increased infection with the Ikeda type. The overall impact experienced by
regions will depend on other factors such as the number of herds present and the
predominant type of farming, as well as the interplay between tick ecology,
cattle immunity and movement patterns of cattle.
PMID- 26436470
TI - Dipeptidyl peptidase-4 inhibitor use in patients with type 2 diabetes and
cardiovascular disease or risk factors.
AB - OBJECTIVES: Management of cardiovascular (CV) risk is an essential aspect of
diabetes care, and acceptable CV risk is a requirement for antidiabetes
medications. Dipeptidyl peptidase-4 (DPP-4) inhibitors effectively reduce
glycated hemoglobin, with a low risk of hypoglycemia and weight gain. The purpose
of this review is to discuss the use of DPP-4 inhibitors in patients with type 2
diabetes mellitus (T2DM) and CV disease or risk factors. METHODS: A PubMed search
(January 2013-June 2015) was conducted to identify prospective trials, meta
analyses, pooled analyses and cohort studies evaluating CV outcomes with DPP-4
inhibitors. RESULTS: Meta-analyses, pooled analyses and retrospective cohort
studies in patients with T2DM suggest no increased CV risk and possible CV
benefit compared with some antidiabetes medications. The three published, long
term, prospective, randomized, double-blind CV outcomes trials in patients with
CV disease or risk factors found no increased rate of major CV events in patients
treated with alogliptin, saxagliptin or sitagliptin versus placebo as add-on to
standard-of-care. However, the analysis of the components of the secondary end
point of the saxagliptin study showed an increased number of hospitalizations for
heart failure (HF) in treated patients versus placebo. A post hoc analysis of the
alogliptin study showed no increase in HF hospitalization in treated patients
with a history of HF versus placebo, but did show an increase in alogliptin
treated patients with no baseline HF history. Sitagliptin showed no increased
risk for HF hospitalization versus placebo in the overall cohort. Two CV outcomes
trials for linagliptin are ongoing. CONCLUSION: The majority of available data
from CV outcomes trials suggest a neutral effect of DPP-4 inhibitors on major CV
events.
PMID- 26436471
TI - Erratum.
PMID- 26436472
TI - Structure of n-Alkyltrichlorosilane Monolayers on Si(100)/SiO2.
AB - The structure of n-alkyltrichlorosilane self-assembled monolayers (SAMs) of alkyl
chain lengths n = 12, 14, 18, and 22 formed on the amorphous native oxide of
silicon (100) has been investigated via angstrom-resolution surface X-ray
scattering techniques, with particular focus on the proliferation of lateral
order along the molecules' long axis. Grazing incidence diffraction shows that
the monolayer is composed of hexagonally packed crystalline-like domains for n =
14, 18, and 22 with a lateral size of about 60 A. However, Bragg rod analysis
shows that ~12 of the CH2 units are not included in the crystalline-like domains.
We assign this, and the limited lateral crystallites' size, to strain induced by
the size mismatch between the optimal chain-chain and headgroup-headgroup
spacings. Analysis of X-ray reflectivity profiles for n = 12, 14, and 22 shows
that the density profile used to successfully model n = 18 provides an excellent
fit where the analysis-derived parameters provide complementary structural
information to the grazing incidence results.
PMID- 26436474
TI - Serum ferritin predicted prognosis in patients with locally advanced pancreatic
cancer.
AB - AIM: The present study evaluated the value of serum ferritin (SF) level for the
prognosis of patients with locally advanced pancreatic cancer (LAPC). PATIENTS &
METHODS: A total of 79 patients with LAPC treated by chemoradiotherapy were
reviewed retrospectively. Pretreatment and post-treatment levels of SF were
obtained. RESULTS: Median progression-free survival (PFS) was 11.8 months; median
overall survival was 18.3 months. A total of 36 patients with elevated SF level
showed significantly worse overall survival and PFS than patients with low SF
level (p = 0.002 and p = 0.004, respectively). In total, 17 patients showed
normal SF level after chemoradiotherapy, and their median PFS was 3.2 months
longer than that of patients whose SF levels were not restored after
chemoradiotherapy. CONCLUSION: SF may serve as a valuable tool to assess
prognosis and monitor chemoradiotherapy response in patients with LAPC.
PMID- 26436475
TI - Ab Initio Unimolecular Reaction Kinetics of CH2C(?O)OCH3 and CH3C(?O)OCH2
Radicals.
AB - The unimolecular dissociation and isomerization kinetics of the methyl ester
combustion intermediates methoxycarbonylmethyl (CH2C(?O)OCH3) and
acetyloxylmethyl (CH3C(?O)OCH2) are theoretically investigated using high-level
ab initio methods and the Rice-Ramsperger-Kassel-Marcus (RRKM)/master equation
(ME) theory. Potential energy surfaces (PESs) are obtained using coupled cluster
singles and doubles with perturbative triples correction (CCSD(T)),
multireference singles and doubles configuration interaction (MRSDCI) with the
Davidson-Silver (DS) correction, and multireference averaged coupled pair
functional (MRACPF2) theory. The transition states exhibit high T1 diagnostics in
coupled cluster calculations, suggesting the need for a multireference correlated
wave function treatment. MRSDCI+DS and MRACPF2 capture their multiconfigurational
character well, yielding lower barrier heights than CCSD(T) for these reactions.
The rate coefficients are computed using the RRKM/ME theory over a 500-2500 K
temperature range and at a pressure range of 0.01 atm to the high-pressure limit.
The temperature- and pressure-dependent rate coefficients are given in modified
Arrhenius expressions. The beta-scission of CH2C(?O)OCH3 is predicted to have a
much higher barrier than the corresponding isomerization reaction and the beta
scission of CH3C(?O)OCH2. Consequently, the rate coefficients for beta-scission
of CH2C(?O)OCH3 are the smallest among the three reactions and the isomerization
followed by decomposition to CH3C(?O) and HCHO is the dominant reaction pathway
for CH2C(?O)OCH3. Both radicals CH2C(?O)OCH3 and CH3C(?O)OCH2 are predicted to
mainly decompose to CH3C(?O) + HCHO rather than to the bimolecular product
CH2C(?O) + CH3O. A newly developed MA combustion mechanism, using our theoretical
rate coefficients for the MA-related reactions, predicts combustion properties in
good agreement with available experimental data.
PMID- 26436476
TI - Assessment of chronic effects of tebuconazole on survival, reproduction and
growth of Daphnia magna after different exposure times.
AB - The effect of the fungicide tebuconazole (0.41, 0.52, 0.71 and 1.14mg/L) on
survival, reproduction and growth of Daphnia magna organisms was monitored using
14 and 21 days exposure tests. A third experiment was performed by exposing D.
magna to the fungicide for 14 days followed by 7 days of recovery (14+7). In
order to test fungicide effects on D. magna, parameters as survival, mean whole
body length, mean total number of neonates per female, mean number of broods per
female, mean brood size per female, time to first brood/reproduction and
intrinsic rate of natural increase (r) were used. Reproduction was seriously
affected by tebuconazole. All tebuconazole concentrations tested affected the
number of broods per female and day to first brood. At 14-days test, number of
neonates per female and body size decreased by concentrations of tebuconazole
higher than 0.52mg/L, whereas at 21-days test both parameters were affected at
all the concentrations tested. Survival of the daphnids after 14 days fungicide
exposure did not exhibited differences among experimental and control groups. In
this experiment r value was reduced (in a 22%) when animals were exposed to
concentrations of 0.71mg/L and 1.14mg/L. Survival of daphnids exposed during 21
days to 1.14mg/L declined, and the intrinsic rate of natural increase (r)
decreased in a 30 % for tebuconazole concentrations higher than 0.41mg/L.
Longevity of daphnids pre-exposed to tebuconazole for 14 days and 7 days in clean
water did not show differences from control values and all of them survived the
21 days of the test. However, after 7 days in fungicide free medium animals were
unable to restore control values for reproductive parameters and length. The
maximum acceptable toxicant concentration (MATC) was calculated using the r
values as parameter of evaluation. MATC estimations were 0.61mg/L and 0.46mg/L
for 14 and 21 days, respectively. Results showed that the number of neonates per
female was the highest sensitive parameter to the effects of tebuconazole on D.
magna. On the other hand, a recovery period of 7 days in a free toxicant medium
would not be longer enough to reestablish normal reproduction parameters in pre
exposed tebuconazole daphnids.
PMID- 26436477
TI - General stress, detoxification pathways, neurotoxicity and genotoxicity evaluated
in Ruditapes philippinarum exposed to human pharmaceuticals.
AB - A battery of biomarkers was evaluated on Ruditapes philippinarum exposed during
14 days to caffeine, ibuprofen, carbamazepine and novobiocin (0.1, 1, 5, 10, 15,
and 50ugL(-1)). The battery included general stress (lysosomal membrane stability
- LMS) analysed in the hemolymph, and biochemical biomarkers analysed in
digestive gland tissues including: biomarkers of phase I (etoxyresorufin O
deethylase - EROD, dibenzylfluorescein dealkylase - DBF), phase II (gluthathione
S-transferase - GST), oxidative stress (gluthathione reductase - GR, gluthathione
peroxidase - GPX, lipid peroxidation - LPO), neurotoxicity (acetylcholinesterase
activity - AChE), and genotoxicity (DNA damage). Pharmaceuticals tested induced
the sublethal responses (even at the environmental range 0.1ugL(-1)). At this low
concentration; caffeine, ibuprofen and carbamazepine decreased the LMS
significantly compared with controls (p<0.05). The four compounds induced
significantly the detoxification metabolism and oxidative stress (p<0.05).
Neurotoxicity was noticed in clams exposed to caffeine and carbamazepine
(p<0.05). Ibuprofen, carbamazepine and novobiocin produced genotoxic effects
(p<0.05). Results from this research validate the use of biomarkers when
assessing the effects of pharmaceuticals within a marine environmental risk
assessment framework, using as a laboratory bioassay model the species R.
philippinarum.
PMID- 26436473
TI - Acetaminophen for Fever in Critically Ill Patients with Suspected Infection.
AB - BACKGROUND: Acetaminophen is a common therapy for fever in patients in the
intensive care unit (ICU) who have probable infection, but its effects are
unknown. METHODS: We randomly assigned 700 ICU patients with fever (body
temperature, >=38 degrees C) and known or suspected infection to receive either 1
g of intravenous acetaminophen or placebo every 6 hours until ICU discharge,
resolution of fever, cessation of antimicrobial therapy, or death. The primary
outcome was ICU-free days (days alive and free from the need for intensive care)
from randomization to day 28. RESULTS: The number of ICU-free days to day 28 did
not differ significantly between the acetaminophen group and the placebo group:
23 days (interquartile range, 13 to 25) among patients assigned to acetaminophen
and 22 days (interquartile range, 12 to 25) among patients assigned to placebo
(Hodges-Lehmann estimate of absolute difference, 0 days; 96.2% confidence
interval [CI], 0 to 1; P=0.07). A total of 55 of 345 patients in the
acetaminophen group (15.9%) and 57 of 344 patients in the placebo group (16.6%)
had died by day 90 (relative risk, 0.96; 95% CI, 0.66 to 1.39; P=0.84).
CONCLUSIONS: Early administration of acetaminophen to treat fever due to probable
infection did not affect the number of ICU-free days. (Funded by the Health
Research Council of New Zealand and others; HEAT Australian New Zealand Clinical
Trials Registry number, ACTRN12612000513819.).
PMID- 26436478
TI - Defining the risk threshold for risk reducing salpingo-oophorectomy for ovarian
cancer prevention in low risk postmenopausal women.
AB - OBJECTIVE: To define risk thresholds for cost-effectiveness of risk-reducing
salpingo-oophorectomy (RRSO) for ovarian cancer (OC) prevention in
low/intermediate risk postmenopausal women. METHODS: A decision-analytic model
compares lifetime costs-&-effects of offering 'RRSO' with 'no RRSO' to
postmenopausal women >=50years for different lifetime OC-risk thresholds: 2%, 4%,
5%, 6%, 8% and 10%. Well established data from the literature are used to
estimate total costs, effects in terms of Quality-Adjusted-Life-Years(QALYs),
cancer incidence, incremental cost-effectiveness ratio(ICER) and impact. Costs
are reported at 2012 prices; costs/outcomes discounted at 3.5%.
Deterministic/probabilistic sensitivity analysis (PSA) evaluate model
uncertainty. RESULTS: RRSO does not save QALYs and is not cost-effective at the
2% general population lifetime OC-risk. At 4% OC-risk RRSO saves QALYs but is not
cost-effective. At risk thresholds >=5%, RRSO saves more life-years and QALYs and
is highly cost-effective. The ICERs for OC-risk levels 5%, 6%, 8% and 10% are
L15,247, L9958, L4584, and L1864 respectively. The gain in life-years from RRSO
equates to 29.2, 40.1, 62.1 and 80.3days at risk thresholds of 5%, 6%, 8% and 10%
respectively. The results are not sensitive to treatment costs of
RRSO/OC/cardiovascular events but are sensitive to utility-scores for RRSO. On
PSA, 67%, 80%, 84%, 91% and 94% of simulations at risk thresholds of 4%, 5%, 6%,
8% and 10% respectively are cost-effective for RRSO. CONCLUSION: RRSO is highly
cost-effective in postmenopausal women aged >50 with >=5% lifetime OC-risk and
increases life-expectancy by >=29.2days. The results could have significant
clinical implications given the improvements in risk prediction and falling costs
of genotyping.
PMID- 26436479
TI - Bayesian cluster identification in single-molecule localization microscopy data.
AB - Single-molecule localization-based super-resolution microscopy techniques such as
photoactivated localization microscopy (PALM) and stochastic optical
reconstruction microscopy (STORM) produce pointillist data sets of molecular
coordinates. Although many algorithms exist for the identification and
localization of molecules from raw image data, methods for analyzing the
resulting point patterns for properties such as clustering have remained
relatively under-studied. Here we present a model-based Bayesian approach to
evaluate molecular cluster assignment proposals, generated in this study by
analysis based on Ripley's K function. The method takes full account of the
individual localization precisions calculated for each emitter. We validate the
approach using simulated data, as well as experimental data on the clustering
behavior of CD3zeta, a subunit of the CD3 T cell receptor complex, in resting and
activated primary human T cells.
PMID- 26436481
TI - Group-DIA: analyzing multiple data-independent acquisition mass spectrometry data
files.
PMID- 26436480
TI - A strategy for dissecting the architectures of native macromolecular assemblies.
AB - It remains particularly problematic to define the structures of native
macromolecular assemblies, which are often of low abundance. Here we present a
strategy for isolating complexes at endogenous levels from GFP-tagged transgenic
cell lines. Using cross-linking mass spectrometry, we extracted distance
restraints that allowed us to model the complexes' molecular architectures.
PMID- 26436484
TI - Mean platelet volume is elevated in exacerbated and convalescent COPD patients.
AB - BACKGROUND: Mean platelet volume (MPV), reflecting the platelet production rate
and stimulation, is an inflammatory marker for cardiovascular disease,
inflammatory bowel disease, and rheumatoid arthritis. However, the associations
between MPV and chronic obstructive pulmonary disease (COPD) are not in
agreement. METHODS: Ninety participants with an exacerbation of COPD were
investigated, and were reassessed when convalescent. Ninety controls were matched
for age, gender, body mass index, smoking index, and medication use. Blood
samples were collected for measurements of MPV and other laboratory data, and
pulmonary function was also assessed. RESULTS: MPV is significantly increased in
convalescent COPD patients compared with healthy controls, and further increased
in COPD patients with an acute exacerbation. MPV was positively correlated with
high-sensitivity C-reactive protein both in the exacerbation and convalescence
periods of COPD, and negatively correlated with FEV1 % predicted and FEV1/FVC in
the convalescent COPD patients. CONCLUSIONS: MPV may be regarded as a quick and
reliable tool in the assessment of inflammatory response in the progression of
COPD.
PMID- 26436482
TI - Noncontact three-dimensional mapping of intracellular hydromechanical properties
by Brillouin microscopy.
AB - Current measurements of the biomechanical properties of cells require physical
contact with cells or lack subcellular resolution. Here we developed a label-free
microscopy technique based on Brillouin light scattering that is capable of
measuring an intracellular longitudinal modulus with optical resolution. The 3D
Brillouin maps we obtained of cells in 2D and 3D microenvironments revealed
mechanical changes due to cytoskeletal modulation and cell-volume regulation.
PMID- 26436483
TI - Apelin/APJ signaling in hypoxia-related diseases.
AB - The regulatory peptide apelin is the endogenous ligand for the orphan G protein
coupled receptor APJ. Apelin and APJ exist in a variety of tissues, with special
status in the heart, lung and tumors. Consequently, the apelin/APJ system exerts
a broad range of activities that affect multiple organ systems. Accumulating
evidence indicates that the expressions of apelin and APJ are significantly
augmented by hypoxia through the hypoxia-inducible factor-1 alpha (HIF-1alpha)
signaling pathway. Increased apelin promotes cellular proliferation, migration
and survival, therefore regulating angiogenesis. In addition, the pre
administration of exogenous apelin is involved in the occurrence and development
of hypoxia-induced pathological diseases. The purpose of this article is to
review the properties of the apelin/APJ system, which is affected by hypoxic
conditions, and the regulation of apelin/APJ signaling in hypoxia-associated
disorders. Thus, the apelin/APJ system may be a potential therapeutic target in
hypoxia-related diseases.
PMID- 26436485
TI - An efficient and robust fatty acid profiling method for plasma metabolomic
studies by gas chromatography-mass spectrometry.
AB - BACKGROUND: Targeted metabolomic analysis of fatty acids has linked the
dysregulation of fatty acids to many diseases. This study selected five
frequently used fatty acid derivatization methods for comparison. METHODS: We
compared the method precisions and derivatization efficiencies, the most
economical and best performing method was subjected to method validation. Twenty
four fatty acid standards were used to validate the method, which was later
applied to the investigation of potential fatty acid markers of breast cancer.
RESULTS: The acetyl chloride method was demonstrated to provide the best
derivatization efficiency and lowest cost for plasma samples. The ionic liquid
column successfully separated positional and geometric fatty acid isomers within
26 min under the optimized conditions. Intra-day and inter-day CVs for most of
the fatty acids were <10%. Over 90% of the results showed recoveries within 85%
115%. The validated method was applied to investigate potential fatty acid
markers of breast cancer. The fatty acid profiling results revealed that 3 fatty
acids (C22:0, C24:0, C18:2n6) were significantly lower in both pre- and post
menopausal breast cancer patients (P<0.05). CONCLUSIONS: We demonstrated that the
proposed method is an accurate, efficient and economical method for plasma
metabolomic studies of fatty acids.
PMID- 26436487
TI - Can electronic stability control replace studded tyres?
AB - Based on recent studies, this paper examines whether an increased use of
electronic stability control can replace studded tyres. A re-analysis of a study
that evaluated the effects on accidents of changes in the use of studded tyres in
major cities in Norway is presented. It is found that if all cars have electronic
stability control, the use of studded tyres can be reduced to about 15 percent
before any increase in the number of accidents occurs. Even if studded tyres were
eliminated entirely, any increase in the number of accidents is likely to be
considerably smaller than it would have been if electronic stability control had
never been invented.
PMID- 26436488
TI - Estimating the human recovery costs of seriously injured road crash casualties.
AB - Road crashes result in substantial trauma and costs to societies around the
world. Robust costing methods are an important tool to estimate costs associated
with road trauma, and are key inputs into policy development and cost-benefit
analysis for road safety programmes and infrastructure projects. With an
expanding focus on seriously injured road crash casualties, in addition to the
long standing focus on fatalities, methods for costing seriously injured
casualties are becoming increasingly important. Some road safety agencies are
defining a seriously injured casualty as an individual that was admitted to
hospital following a road crash, and as a result, hospital separation data
provide substantial potential for estimating the costs associated with seriously
injured road crash casualties. The aim of this study is to establish techniques
for estimating the human recovery costs of (non-fatal) seriously injured road
crash casualties directly from hospital separation data. An individuals' road
crash-related hospitalisation record and their personal injury insurance claim
were linked for road crashes that occurred in New South Wales, Australia. These
records provided the means for estimating all of the costs to the casualty
directly related to their recovery from their injuries. A total of 10,897
seriously injured road crash casualties were identified and four methods for
estimating their recovery costs were examined, using either unit record or
aggregated hospital separation data. The methods are shown to provide robust
techniques for estimating the human recovery costs of seriously injured road
crash casualties, that may prove useful for identifying, implementing and
evaluating safety programmes intended to reduce the incidence of road crash
related serious injuries.
PMID- 26436489
TI - A quarter century of the Pacific Basin Consortium: looking back to move forward.
AB - The Pacific Basin Consortium (PBC) was formed 25 years ago to address significant
public health challenges to vulnerable populations imposed by environmental
threats in the region, including areas surrounding the rim of and in the Pacific
Ocean. Originally focused on toxic waste pollution, the PBC has broadened its
efforts over the years, embracing a health focus and more of a balance between
engineering and public health. This move was informed by the PBC's close
relationship with the National Institutes of Health (NIH) National Institute of
Environmental Health Sciences (NIEHS) Superfund Hazardous Substances Basic
Research and Training Program (Superfund Research Program, or SRP), which played
a dynamic role in the PBC from its early days. In addition, a sub-focus on
children's environmental health emerged, which helped set the agenda for
children's environmental health research in the region. Progress has also been
made in reducing harm from some threats, particularly via extensive interventions
to remediate arsenic in drinking water in Bangladesh, western Thailand, and
Vietnam. However, many of the environmental health problems in the Pacific Basin
region persist, including air pollution, inadequate safe drinking water,
undernutrition, and a growing electronic waste problem. In the Pacific Basin and
elsewhere, people with the lowest incomes often live in areas with the worst
pollution. Although it is difficult to implement, dynamic strategic networking
efforts are vital to understanding and correcting the inequities that persist in
global environmental health. The PBC can help accomplish this by continuing and
expanding its work to foster and enhance collaborations and communications
between environmental health and engineering investigators and to integrate
investigator-initiated research. As the PBC looks forward, there is also a need
to exert increased effort to establish and maintain partnerships, to develop
community-based primary-care and health services for vulnerable populations, as
well as to connect with researchers in the eastern side of the Pacific basin and
those in smaller island states.
PMID- 26436490
TI - Robust decoding of selective auditory attention from MEG in a competing-speaker
environment via state-space modeling.
AB - The underlying mechanism of how the human brain solves the cocktail party problem
is largely unknown. Recent neuroimaging studies, however, suggest salient
temporal correlations between the auditory neural response and the attended
auditory object. Using magnetoencephalography (MEG) recordings of the neural
responses of human subjects, we propose a decoding approach for tracking the
attentional state while subjects are selectively listening to one of the two
speech streams embedded in a competing-speaker environment. We develop a
biophysically-inspired state-space model to account for the modulation of the
neural response with respect to the attentional state of the listener. The
constructed decoder is based on a maximum a posteriori (MAP) estimate of the
state parameters via the Expectation Maximization (EM) algorithm. Using only the
envelope of the two speech streams as covariates, the proposed decoder enables us
to track the attentional state of the listener with a temporal resolution of the
order of seconds, together with statistical confidence intervals. We evaluate the
performance of the proposed model using numerical simulations and experimentally
measured evoked MEG responses from the human brain. Our analysis reveals
considerable performance gains provided by the state-space model in terms of
temporal resolution, computational complexity and decoding accuracy.
PMID- 26436491
TI - The impact of transoral robotic surgery on the overall treatment of oropharyngeal
cancer patients.
AB - OBJECTIVES/HYPOTHESIS: To assess adjuvant therapy in patients undergoing surgical
management of oropharyngeal squamous cell carcinoma (OPSCCA) with transoral
robotic surgery (TORS) and neck dissection. STUDY DESIGN: A prospective,
nonrandomized, consecutive patient series from two separate protocols in a
tertiary academic medical center. METHODS: Patients undergoing treatment for
OPSCCA were selected from a prospective protocol evaluating functional and
oncologic outcomes following TORS with a comparator group of OPSCCA patients
receiving definitive chemoradiotherapy (CRT) participating in a separate
prospective protocol. RESULTS: Forty-two patients represented the TORS group and
38 the CRT group. Twenty (48%) of the TORS patients received surgery only,
whereas nine (21%) underwent adjuvant radiotherapy and 13 (31%) adjuvant CRT.
Adjuvant therapy patients had a higher overall T (P =.0007) and N (P < .0001)
stage than the TORS-only group. Surgery resulted in stage changes in 18 (43%)
patients, leading to alteration in therapy for nine (21%) patients. The 3-year
overall survival (OS), disease-specific survival (DSS), and locoregional control
was 74% versus 90% (P = .30), 94% versus 94% (P = .91), and 72% versus 91% (P =
.19) for the TORS-alone versus TORS plus adjuvant therapy groups, respectively.
Comparison with the CRT group revealed a survival benefit in the TORS group
approaching significance, with a 3-year OS of 83% versus 57% (P = .06) and DSS of
94% versus 85% (P = .08), respectively. CONCLUSIONS: Primary surgical management
of OPSCCA with TORS and neck dissection provides accurate staging information,
which can lead to the appropriate selection of subsequent therapy. This approach
does not compromise survival and warrants additional investigation. LEVEL OF
EVIDENCE: 3b.
PMID- 26436492
TI - Relationship between polymorphisms in the proline dehydrogenase gene and
schizophrenia risk.
AB - Previous studies have suggested that an association exists between the proline
dehydrogenase gene (PRODH) and increased schizophrenia risk. We examined the
prevalence of the PRODH 757C/T (Arg185Trp), 1766A/G (Gly521Arg), and 1852G/A
(intronic mutation) polymorphisms in 175 patients with schizophrenia and 185
control subjects. All subjects were of Iranian ancestry. The PRODH 757TT, 1852AA,
and 1766GG genotypes were associated with an increased risk of schizophrenia
(odds ratio = 1.38, 95% confidence interval: 0.88-2.16, P = 0.001, P = 0.001,
respectively). The activity alleles in the PRODH genotype combinations were
associated with an increased risk of schizophrenia (haplotype analysis, TAG
genotype P = 0.007). Our findings support a major role for the PRODH 757TT,
1766GG, and 1852AA genotypes alone and in combination for schizophrenia
susceptibility.
PMID- 26436493
TI - Risk factors associated with aortic remodeling in patients with Stanford type B
aortic dissection after thoracic endovascular aortic repair.
AB - To determine the risk factors associated with adverse aortic remodeling after
thoracic endovascular aortic repair (TEVAR) in patients with Stanford type B
aortic dissection, we performed a retrospective analysis of 54 patients between
January 2009 and June 2012 at the First Affiliated Hospital of Soochow
University. All patients underwent TEVAR of the descending thoracic aorta.
Multiple-logistic regression analyses were performed to identify risk factors
associated with aortic remodeling. True-lumen and false-lumen volumes were
increased (P < 0.001) and decreased (P < 0.001) after surgery, respectively.
Therefore, the remodeling index increased after surgery (1.04 +/- 0.6 to 2.06 +/-
1.12, P < 0.001). Remodeling index and true-lumen volume were higher in the
favorable aortic remodeling group compared to the adverse aortic remodeling group
(P < 0.001), while the false-lumen volume was lower in the favorable aortic
remodeling group (P < 0.001). Multivariate analyses revealed a branch originating
from the false lumen (OR = 39.9, P < 0.01) and multiple tears (OR = 27.4, P <
0.01) to be independent risk factors for adverse aortic remodeling. Therefore, a
branch originating from the false lumen and multiple tears were determined to be
independent risk factors for adverse aortic remodeling after TEVAR in patients
with Stanford type B aortic dissection.
PMID- 26436494
TI - Effect of p53 gene polymorphism on functions of prostate cancer cells.
AB - Prostate cancer cells were transfected with plasmids [empty plasmids, wild-type
pcDNA3.1-p53 (V/V), mutant type pcDNA3.1- p53 (G/G)] to analyze the effect of p53
gene polymorphisms on the proliferation, cycle, and apoptosis of prostatic cancer
cells. Empty plasmids containing wild-type pcDNA3.1-p53 (V/V) and mutant type
pcDNA3.1- p53 (G/G) were used to transfect PC3 and LNCaP cells, respectively.
Cell proliferation was detected at 0, 24, 48, and 72 h using the MTT method.
Cells were collected at 24 and 72 h. The distribution of cell cycles in various
groups was detected using flow cytometry (propidium iodide staining method) and
the apoptosis rate was detected using annexin V + propidium iodide double
staining. Compared with the control group, wild-type pcDNA3.1-p53 (V/V) and
mutant type pcDNA3.1-p53 (G/G) showed a significant inhibitory effect on cell
proliferation (P < 0.05); the inhibitory effect of the mutant type was stronger
than that of the wild-type. There was no significant difference between PC3 cells
and LNCaP cells. After transfection with wild-type pcDNA3.1-p53 (V/V) and mutant
type pcDNA3.1-p53 (G/G), PC3 and LNCaP cells were arrested in the G0/G1 stage.
Transfection with pcDNA3.1-p53 (G/G) showed a more significant effect than
transfection with pcDNA3.1-p53 (V/V). Both the wild-type pcDNA3.1-p53 (V/V) and
mutant-type pcDNA3.1-p53 (G/G) led to an increased apoptosis rate of PC3 and
LNCaP cells. The p53 gene polymorphism affects the proliferation, apoptosis, and
cycle of prostate cancer cells and may serve as a reliable index for the
diagnosis and treatment of prostate cancer.
PMID- 26436495
TI - Prevalence of CCR5-Delta32 and CCR2-V64I polymorphisms in a mixed population from
northeastern Brazil.
AB - Chemokines are low-molecular weight proteins that play a key role in inflammatory
processes. Genomic variations in chemokine receptors are associated with the
susceptibility to various diseases. Polymorphisms in chemokine receptor type 5
(CCR5)-Delta32 and CCR2-V64I are related to human immunodeficiency virus
infection resistance, which has led to genetic association studies for several
other diseases. Given the heterogeneous distribution of these polymorphisms in
different global populations and within Brazilian populations, we analyzed the
prevalence of CCR5-Delta32 and CCR2-V64I polymorphisms in a mixed population from
northeastern Brazil. The study included 223 individuals from the general
population of the city of Parnaiba, Piaui, who had a mean age of 73 years. Of
these individuals, 37.2% were men and 62.8% were women. Polymorphisms were
analyzed using DNA extracted from peripheral blood leukocytes by using polymerase
chain reaction alone (CCR5-Delta32) or accompanied by restriction endonuclease
digestion (CCR2-V64I). In both cases, the genotypes were determined using 8%
polyacrylamide gel electrophoresis and silver nitrate staining. The population
conformed to Hardy-Weinberg equilibrium for both the loci studied. No individuals
were homozygous for allele-Delta32, which was present in 1.8% of the population,
whereas allele-64I was present in 13.9% of the participants studied; 74.9% were
homozygous for the wild-type allele, while 22.4 and 2.7% were heterozygous and
homozygous for the mutant allele, respectively. Additional studies are needed to
investigate the relationship between these polymorphisms and disease
etiopathogenesis in reference populations.
PMID- 26436496
TI - Endo-beta-mannanase and beta-tubulin gene expression during the final phases of
coffee seed maturation.
AB - Coffee seeds begin to develop shortly after fertilization and can take 6 to 8
months to complete their formation, a period during which all the characteristics
of the mature seed are determined, directly influencing physiological quality.
However, little is known about the molecular mechanisms that act during coffee
seed maturation. The objective of the current study was to analyze expression of
the beta-tubulin (TUB) and endo-beta-mannanase (MAN) genes during different
phases at the end of development and in different tissues of Coffea arabica
seeds. The transcription levels of the TUB and MAN genes were quantified in a
relative manner using qRT-PCR in whole seeds, and dissected into embryos and
endosperms at different developmental stages. Greater expression of MAN was
observed in whole seeds and in endosperms during the green stage, and in the
embryo during the over-ripe stage. High TUB gene expression was observed in whole
seeds during the green stage and, in the embryos, there were peaks in expression
during the over-ripe stage. In endosperms, the peak of expression occurred in
both the green stage and in the cherry stage. These results suggest participation
of endo-beta-mannanase during the initial seed developmental stages, and in the
stages of physiological maturity in the embryo tissues. TUB gene expression
varied depending on the developmental stage and section of seed analyzed,
indicating the participation of beta-tubulin during organogenesis and coffee seed
maturation.
PMID- 26436497
TI - Screening of crucial long non-coding RNAs in oral epithelial dysplasia by serial
analysis of gene expression.
AB - Oral epithelial dysplasia (OED) is a premalignant lesion of the oral mucosa.
Considering the poor 5-year survival rate of oral cancer, further investigation
is needed in order to determine the pathogenesis of OED. In the present study,
serial analysis of gene expression (SAGE) data from patients with OED were
compared to normal controls to identify differentially expressed genes (DEGs).
SAGE data were obtained from the Gene Expression Omnibus, and included samples
from patients with mild, moderate, or severe dysplasia. The DEGs were identified
using the edgeR software package and functional-enrichment analysis was performed
with the DAVID (https://david.ncifcrf.gov/) software program. The co-expression
network was constructed using the CoExpress software and target genes of long non
coding RNAs (lncRNAs) were predicted according to the proximity between the
lncRNAs and mRNAs in the genome. A total of 517 DEGs were identified, including
409 mRNAs and 108 lncRNAs. Functional-enrichment analysis showed that mRNAs and
lncRNAs involved in epithelial cell differentiation, epithelium development, and
epidermal cell differentiation were significantly enriched in the DEGs. Thirty
eight potential regulatory relationships were unveiled between lncRNAs and mRNAs,
and two subnetworks were discovered by analyzing the topological properties of
the co-expression network. In conclusion, we have identified key mRNAs and
lncRNAs in OED, and these findings may aid in understanding the pathogenesis of
OED and advance potential future treatments.
PMID- 26436498
TI - Molecular identification of Fusarium species isolated from transgenic insect
resistant cotton plants in Mexicali valley, Baja California.
AB - Cotton production in the Mexicali valley is adversely affected by wilt and root
rot disease associated with Fusarium species. In the present study, we sought to
isolate and identify the Fusarium species in the rhizosphere of transgenic insect
resistant cotton plants grown in the Mexicali valley. Our analyses isolated four
native fungi from the rhizosphere of cotton plants, namely, T-ICA01, T-ICA03, T
ICA04, and T-ICA08. These fungal isolates were categorized as belonging to
Fusarium solani using their phenotypic characteristics and ITS region sequence
data. Examination of the infection index showed that T-ICA03 and T-ICA04 caused
systemic colonization (90%) of seeds followed by the occurrence of radicle and
coleoptile decay. In contrast, T-ICA08 strain was less pathogenic against seed
tissues (40%) in comparison to the other strains isolated. Our study showed that
in transgenic insect-resistant cotton the disease "Fusarium wilt" is caused by
the fungus, F. solani. Future studies are necessary to characterize the F. solani
populations to determine whether phenological stages might influence the genetic
diversity of the fungal populations present.
PMID- 26436499
TI - Male-specific association of the APC rs383830 T allele with the risk of coronary
heart disease.
AB - APC is a tumor suppressor gene that is involved in the processes of cell
migration and adhesion, transcriptional activation, and apoptosis. The goal of
this study was to evaluate the contribution of the APC rs383830 polymorphism to
coronary heart disease (CHD) in Han Chinese. A total of 783 patients with CHD and
737 controls were tested in the current association study. Although our study did
not identify an association between the APC rs383830 polymorphism and CHD, a
breakdown analysis by gender indicated there was a significant contribution of
the rs383830 T allele to the risk of CHD in males (P = 0.046, odds ratio = 1.267,
95% confidence interval = 1.004-1.598). In conclusion, our study suggested a male
specific association of the APC rs383830 polymorphism with CHD.
PMID- 26436500
TI - Unraveling systematic inventory of Echinops (Asteraceae) with special reference
to nrDNA ITS sequence-based molecular typing of Echinops abuzinadianus.
AB - The present study explored the systematic inventory of Echinops L. (Asteraceae)
of Saudi Arabia, with special reference to the molecular typing of Echinops
abuzinadianus Chaudhary, an endemic species to Saudi Arabia, based on the
internal transcribed spacer (ITS) sequences (ITS1-5.8S-ITS2) of nuclear ribosomal
DNA. A sequence similarity search using BLAST and a phylogenetic analysis of the
ITS sequence of E. abuzinadianus revealed a high level of sequence similarity
with E. glaberrimus DC. (section Ritropsis). The novel primary sequence and the
secondary structure of ITS2 of E. abuzinadianus could potentially be used for
molecular genotyping.
PMID- 26436501
TI - Effectiveness evaluation of dendritic cell immunotherapy for osteosarcoma on
survival rate and in vitro immune response.
AB - The aim of this study was to investigate the effects of dendritic cell (DC)
therapy in osteosarcoma. Bone marrow DCs from Wistar (allograft group) and
Sprague Dawley (SD) (homograft group) rats were electrically fused with the SD
derived osteosarcoma cell line UMR106 to generate a DC-osteosarcoma fusion (DOF)
tumor vaccine, which was co-incubated with SD T lymphocytes to stimulate T cell
proliferation. CD8+ and CD4+ cell percentages were measured by flow cytometry;
tumor-cytotoxic effects of cytotoxic T lymphocytes (CTLs) were measured by the
MTT assay. Active immunotherapy was applied to SD osteosarcoma model rats via
subcutaneous injection of the tumor vaccine. Significant potentiation of T
lymphocyte proliferation was observed in both groups. In the homograft group, the
CD8+/CD4+ ratio was elevated to 78.2 from 55.1% after stimulation (P < 0.05)
whereas the CD4+ cell percentage was reduced from 61.3 to 21.2% (P < 0.05).
Similarly, in the allograft group the CD8+ and CD4+ cell percentages
significantly increased (33.8 to 69.6%) or decreased (61.3 to 28.1%) after
stimulation, respectively (P < 0.05). The preferential homograft group response
was not significant (P > 0.05). Induced UMR106- specific CTLs showed a
significantly higher tumor-cytotoxic effect after stimulation (P < 0.05). After
DOF active immunotherapy, tumor bodies displayed atrophy or disappearance,
leading to higher survival times and rates (60 and 70% in the allograft and
homograft groups) (P < 0.05). This study demonstrated that osteosarcoma
immunotherapy using a DC-fused tumor vaccine can effectively stimulate T
lymphocyte proliferation and induce the tumor-cytotoxic activity of CTLs.
PMID- 26436502
TI - Thermotherapy-induced reduction in glioma invasiveness is mediated by tumor
necrosis factor-alpha.
AB - Thermotherapy has been proven to be effective for the treatment of various
tumors, including glioma. We determined whether tumor necrosis factor-alpha (TNF
alpha) is involved in the regulation of the biological processes of glioma
development. Reverse transcription-polymerase chain reaction (RT-PCR) and
immunocytochemistry were used to investigate the levels of TNF-alpha mRNA and
heat shock factor-1 (HSF1) protein, respectively, in glioma cells.
Radioimmunoassay was used to dynamically monitor the contents of TNF-alpha in the
nutrient fluid of C6 cells after thermotherapy treatment. Crystal violet staining
was used to determine glioma invasiveness. The most obvious increases in HSF1
protein and TNF-alpha mRNA in C6 cells were observed at 30 and 60 min after
thermotherapy, respectively. In addition, the radioactivity of TNF-alpha in the
culture fluid of the C6 cells reached a peak after 120 min of thermotherapy. In
addition, glioma invasiveness decreased and the concentration of TNF-alpha
reached a maximum after 120 min of thermotherapy. Our results show that the
decrease in thermotherapy-mediated glioma invasiveness is due to the accelerated
release of TNF-alpha, which could promote the release of HSF1 from neurospongioma
cells.
PMID- 26436503
TI - Identification of natural recombinants derived from PCV2a and PCV2b.
AB - Porcine circovirus type 2 (PCV2) is considered to be the main pathogen in PC
associated diseases, and significantly affects the global pig-producing industry.
PCV2 continuously evolves by point mutations and genome recombinations. In the
present study, we aimed to further identify recombinant PCV2 strains. We used
polymerase chain reaction to detect PCV2 in the carcasses of pigs with suspected
infections from different regions of Guangdong Province in China. DNA was
extracted from samples with confirmed infection and full- genome amplification,
sequencing, phylogenetic tree construction, gene recombination detection, and
sequence alignment were performed in gene recombination analysis. Our results
show that recombination occurred between the strains SHC (DQ104421) and ZhuJi2003
(AY579893). The recombination resulted in three recombinants: GD003 (KM503044),
GD005 (KM487708), and GD008 (KM487709). Further analyses revealed that these
novel recombinants appeared to result from recombination between the PCV2a and
PCV2b strains, with crossover regions located in ORF2. This study was a
comprehensive analysis that used several different methods, which demonstrated
that a cluster of PCV2 strains resulted from the same type of inter-genotypic
recombination pattern, with a breakpoint in the structural protein coding region.
The results of our study provide both information on the recombination mechanism
and disease pathogenesis and useful data for the prevention of PCV2 in the swine
industry.
PMID- 26436504
TI - Prediction of protein-protein interactions using chaos game representation and
wavelet transform via the random forest algorithm.
AB - Studying the network of protein-protein interactions (PPIs) will provide valuable
insights into the inner workings of cells. It is vitally important to develop an
automated, high-throughput tool that efficiently predicts protein-protein
interactions. This study proposes a new model for PPI prediction based on the
concept of chaos game representation and the wavelet transform, which means that
a considerable amount of sequence-order effects can be incorporated into a set of
discrete numbers. The advantage of using chaos game representation and the
wavelet transform to formulate the protein sequence is that it can more
effectively reflect its overall sequence-order characteristics than the
conventional correlation factors. Using such a formulation frame to represent the
protein sequences means that the random forest algorithm can be used to conduct
the prediction. The results for a large-scale independent test dataset show that
the proposed model can achieve an excellent performance with an accuracy value of
about 0.86 and a geometry mean value of about 0.85. The model is therefore a
useful supplementary tool for PPI predictions. The predictor used in this article
is freely available at http://www.jci-bioinfo.cn/PPI.
PMID- 26436505
TI - DNA genetic artificial fish swarm constant modulus blind equalization algorithm
and its application in medical image processing.
AB - This study proposes use of the DNA genetic artificial fish swarm constant modulus
blind equalization algorithm (DNA-G-AFS-CMBEA) to overcome the local convergence
of the CMBEA. In this proposed algorithm, after the fusion of the fast
convergence of the AFS algorithm and the global search capability of the DNA-G
algorithm to drastically optimize the position vector of the artificial fish, the
global optimal position vector is obtained and used as the initial optimal weight
vector of the CMBEA. The result of application of this improved method in medical
image processing demonstrates that the proposed algorithm outperforms the CMBEA
and the AFS-CMBEA in removing the noise in a medical image and improving the peak
signal to noise ratio.
PMID- 26436506
TI - Expression of claudin-1 and its relationship with lymphatic microvessel
generation in hypopharyngeal squamous cell carcinoma.
AB - We investigated the relationship between claudin-1 and micro-lymphatic vessel
density (MLVD) by detecting claudin-1 and protein D2-40 expression in cancer
tissue specimens obtained from 97 patients with hypopharyngeal squamous cell
carcinoma (HSCC). We also explored the correlation between the expression of
these proteins and clinical tumor stage, pathological grading, and clinical
prognosis in the patients. Moreover, we studied the mechanism of lymph node
metastasis in HSCC, thereby providing information for treating HSCC and
inhibiting lymph node metastasis. We detected levels of claudin-1 and protein D2
40 expression in cancer tissue from 97 patients with HSCC and para-tumor tissue
from 90 patients by immunohistochemistry; we analyzed the correlation between
markers and clinicopathological features by using the Pearson chi-square test and
conducted survival analysis by the log-rank test. Claudin-1 expression was high
in HSCC and was related to tumor differentiation and lymph node metastasis;
Kaplan-Meier analysis showed that claudin-1 expression was related to patient
survival rate (P = 0.012). There was a significant relationship between MLVD in
the tissues adjacent to the carcinoma and the indices of histopathological grade,
clinical stage, and lymph node metastasis. There was also a positive correlation
between claudin-1 expression and MLVD. High expression of claudin-1 might induce
the generation of tumor lymphatic vessels, which increases metastasis in the
lymph node. Because claudin-1 is related to patient survival rate, it may be
useful as a monitoring index for postoperative HSCC and might be a new target for
treating the disease.
PMID- 26436507
TI - Identification of genes involved in spontaneous leaf color variation in
Pseudosasa japonica.
AB - Spontaneous leaf color variation in bamboo provides the opportunity to study the
mechanisms of leaf color formation and the breeding of ornamental bamboos.
Despite the fact that many genes are known to be involved in leaf color variation
in model plants, molecular mechanisms governing natural leaf color variation in
bamboo have remained obscure. This study aimed to identify the genes responsible
for the occurrence of such phenomena in bamboo using the suppression subtractive
hybridization (SSH) method between green and albino leaves in Pseudosasa japonica
f. A total of 1062 and 1004 differentially expressed transcripts were obtained
from the forward and reverse SSH libraries, respectively. Subsequently, 59
differentially expressed unigenes with potential roles in leaf color formation,
predicted via computational analysis of their functional relevance, were selected
for further analysis using qPCR. Ten genes, involved in photosynthesis, plastid
development, and cation signal transduction, showed 2-fold changes in expression
levels between green and albino leaves. Further expression pattern analyses of
these genes at three developmental stages revealed much lower expression
abundance of Lhca1-encoded chlorophyll a/b binding protein in the albino leaves
than in the green leaves. Our results suggest that, together with the
concatenated negative pressure for subsequent photosynthetic processes, the
albino phenotype is at least partly attributable to chloroplast inner membrane
damage or to the impairment of photosynthetic pigment accumulation, which results
from low Lhca1 expression.
PMID- 26436508
TI - High yield of functional metagenomic library from mangroves constructed in fosmid
vector.
AB - In the present study, metagenomic technique and fosmid vectors were used to
construct a library of clones for exploring the biotechnological potential of
mangrove soils by isolation of functional genes encoding hydrolytic enzymes. The
library was built with genomic DNA from the soil samples of mangrove sediments
and the functional screening of 1824 clones (~64 Mbp) was performed to detect the
hydrolytic activity specific for cellulases, amylases (at acidic, neutral and
basic pH), lipases/esterases, proteases, and nitrilases. Significant numbers of
clones, positive for the tested enzyme activities were obtained. Our results
indicate the importance and biotechnological potential of mangrove soils
especially when compared to those obtained using other soil metagenomic
libraries.
PMID- 26436509
TI - Genome-wide identification of copy number variations in Holstein cattle from Baja
California, Mexico, using high-density SNP genotyping arrays.
AB - Copy number variations (CNVs) are an important source of genomic structural
variation, and can be used as markers to investigate phenotypic and economic
traits. CNVs also have functional effects on gene expression and can contribute
to disease susceptibility in mammals. Currently, single nucleotide polymorphism
genotyping arrays (SNP chips) are the technology of choice for identifying CNV
variations. Microarray technologies have recently been used to study the bovine
genome. The objective of the present study was to develop CNVs in Holstein cows
from the Northwest of Mexico using the Affymetrix Axiom Genome-Wide BOS 1 Array,
which assays 648,315 SNPs and provides a wide coverage for genome-wide studies.
We applied the two most widely used algorithms for the discovery of CNVs (PennCNV
and QuantiSNP) and found 56 CNV regions (CNVRs) representing 0.33% of the bovine
genome (8.46 Mb). These CNVRs ranged from 1.5 to 970.8 kb with an average length
of 151 kb. They involved 103 genes and showed a 28% overlap with CNVRs already
reported. Of the 56 CNVRs found, 20 were novel. In this study we present the
first genomic analysis of CNVs in Mexican cattle using high-density SNP data. Our
results provide a new reference basis for future genomic variation and
association studies between CNVs and phenotypes, especially in Mexican cattle.
PMID- 26436510
TI - Significance of Ebp1 and p53 protein expression in cervical cancer.
AB - In this study, the ErbB3-binding protein (Ebp1) and p53 protein expression in
cervical cancer tissues, and its significance in the prognosis of the disease was
investigated. Ebp1 and p53 protein expression was detected by immunohistochemical
analysis in cervical cancer tissues (N = 60) and normal tissues adjacent to the
cancer tissues (N = 60). The rates of positive Ebp1 and p53 protein expression
were 35.0 and 60.0%, respectively. Ebp1 and p53 were overexpressed in cervical
cancer tissues, compared to normal tissues (P < 0.05). Ebp1 and p53 protein
expression was not correlated with age, tumor size, or family tumor history (P >
0.05). However, high levels of expression of Ebp1 and p53 were positively
correlated with the TNM stage and lymphatic metastasis in cervical cancer
patients (P < 0.05). The combined determination of Ebp1 and p53 expression levels
in cervical cancer patients could support the effective prediction of metastatic
potential and patient prognosis.
PMID- 26436511
TI - Short Communication: Elucidation of bacterial community structure on thin-spined
porcupine (Chaetomys subspinosus) spines by denaturing.
AB - Thin-spined porcupines (Chaetomys subspinosus) are threatened with extinction and
are categorized as vulnerable. This is because of alteration to and loss of their
habitat and possible hunting activities in their distribution area. Their spines
constitute one of their defense mechanisms, which can be fomites for pathogens to
humans. However, little is known about such pathogens. The present study aimed to
detect bacteria on spines of C. subspinosus, from the Una Biological Reserve,
South of Bahia, northeastern Brazil, by analyzing metagenomic DNA, isolating
bacterial culture, using the denaturing gradient gel electrophoresis (DGGE)
technique, and sequencing. Six anatomical points were selected for withdrawing
spine samples from an individual C. subspinosus. At all sample points, bacteria
were detected by bacteriological culture and/or DGGE and sequencing of excised
bands. When all samples were combined, standard PCR-DGGE analysis of bacteria
present in the spines identified 15 distinct bands, thereby revealing a distinct
bacterial community. The main pathogens identified through sequencing were
Bacillus cereus, B. thuringiensis, B. anthracis, and B. pumilus. The present
study demonstrated the isolation and identification of non-pathogenic and
pathogenic bacteria on the spines of C. subspinosus.
PMID- 26436512
TI - Iron-Catalyzed Decarboxylation of Trifluoroacetate and Its Application to the
Synthesis of Trifluoromethyl Thioethers.
AB - Nucleophilic CF3 has been generated by decarboxylation of potassium
trifluoroacetate, arguably the most easy-to-handle, inexpensive, and sustainable
source of trifluoromethyl groups. Simple iron(II) chloride catalyzes the
decarboxylation as well as a subsequent trifluoromethylation of
organothiocyanates, resulting in a straightforward synthesis of trifluoromethyl
thioethers. The KCN byproduct is absorbed by iron(II) with formation of nontoxic
potassium hexacyanoferrate. An analogous trifluoromethylation of aldehydes with
trifluoroacetate underlines the synthetic potential of such iron-catalyzed
decarboxylative trifluoromethylations.
PMID- 26436513
TI - Concentrations, Trends, and Air-Water Exchange of PAHs and PBDEs Derived from
Passive Samplers in Lake Superior in 2011.
AB - Polycyclic aromatic hydrocarbons (PAHs) and polybrominated diphenylethers (PBDEs)
are both currently released into the environment from anthropogenic activity.
Both are hence primarily associated with populated or industrial areas, although
wildfires can be an important source of PAHs, as well. Polyethylene passive
samplers (PEs) were simultaneously deployed in surface water and near surface
atmosphere to determine spatial trends and air-water gaseous exchange of 21 PAHs
and 11 PBDEs at 19 sites across Lake Superior in 2011. Surface water and
atmospheric PAH concentrations were greatest at urban sites (up to 65 ng L(-1)
and 140 ng m(-3), respectively, averaged from June to October). Near populated
regions, PAHs displayed net air-to-water deposition, but were near equilibrium
off-shore. Retene, probably depositing following major wildfires in the region,
dominated dissolved PAH concentrations at most Lake Superior sites. Atmospheric
and dissolved PBDEs were greatest near urban and populated sites (up to 6.8 pg L(
1) and 15 pg m(-3), respectively, averaged from June to October), dominated by
BDE-47. At most coastal sites, there was net gaseous deposition of BDE-47, with
less brominated congeners contributing to Sault Ste. Marie and eastern open lake
fluxes. Conversely, the central open lake and Eagle Harbor sites generally
displayed volatilization of PBDEs into the atmosphere, mainly BDE-47.
PMID- 26436516
TI - Metal-ligand cooperation.
AB - Metal-ligand cooperation (MLC) has become an important concept in catalysis by
transition metal complexes both in synthetic and biological systems. MLC implies
that both the metal and the ligand are directly involved in bond activation
processes, by contrast to "classical" transition metal catalysis where the ligand
(e.g. phosphine) acts as a spectator, while all key transformations occur at the
metal center. In this Review, we will discuss examples of MLC in which 1) both
the metal and the ligand are chemically modified during bond activation and 2)
bond activation results in immediate changes in the 1st coordination sphere
involving the cooperating ligand, even if the reactive center at the ligand is
not directly bound to the metal (e.g. via tautomerization). The role of MLC in
enabling effective catalysis as well as in catalyst deactivation reactions will
be discussed.
PMID- 26436518
TI - Measuring Carbapenem-Resistant Enterobacteriaceae in the United States: A
Critical Step for Control.
PMID- 26436519
TI - Adjusting for Confounding in Early Postlaunch Settings: Going Beyond Logistic
Regression Models.
AB - BACKGROUND: Postlaunch data on medical treatments can be analyzed to explore
adverse events or relative effectiveness in real-life settings. These analyses
are often complicated by the number of potential confounders and the possibility
of model misspecification. METHODS: We conducted a simulation study to compare
the performance of logistic regression, propensity score, disease risk score, and
stabilized inverse probability weighting methods to adjust for confounding. Model
misspecification was induced in the independent derivation dataset. We evaluated
performance using relative bias confidence interval coverage of the true effect,
among other metrics. RESULTS: At low events per coefficient (1.0 and 0.5), the
logistic regression estimates had a large relative bias (greater than -100%).
Bias of the disease risk score estimates was at most 13.48% and 18.83%. For the
propensity score model, this was 8.74% and >100%, respectively. At events per
coefficient of 1.0 and 0.5, inverse probability weighting frequently failed or
reduced to a crude regression, resulting in biases of -8.49% and 24.55%. Coverage
of logistic regression estimates became less than the nominal level at events per
coefficient <=5. For the disease risk score, inverse probability weighting, and
propensity score, coverage became less than nominal at events per coefficient
<=2.5, <=1.0, and <=1.0, respectively. Bias of misspecified disease risk score
models was 16.55%. CONCLUSION: In settings with low events/exposed subjects per
coefficient, disease risk score methods can be useful alternatives to logistic
regression models, especially when propensity score models cannot be used.
Despite better performance of disease risk score methods than logistic regression
and propensity score models in small events per coefficient settings, bias, and
coverage still deviated from nominal.
PMID- 26436521
TI - On-line preconcentration strategy for the simultaneous quantification of three
local anesthetics in human urine using CZE.
AB - The simultaneous determination of usually employed anesthetics (procaine,
lidocaine, and bupivacaine) has been developed and validated using CE with
ultraviolet detection at 212 nm. The separation of these three drugs has been
achieved in less than 7 min, using a temperature of 25oC and 25 kV, with a 150 mM
citrate buffer (pH 2.5) as BGE. Field-amplified sample injection (FASI) has been
used for on-line sample preconcentration. Ultrapure water and ACN 50/50 (v/v)
mixture gave the greatest enhancement factor when it was employed as an injection
solvent. Injection voltage and time were optimized, being 13 kV and 13 s, the
optimum values, respectively. To avoid the possible irreproducibility associated
with the electrokinetic injection, an internal standard such as tetracaine, was
employed. The instrumental detection limits (LOD S/N = 3) for the compounds
ranged between 2.6 and 7.0 MUg L(-1) and the quantitation limits (LOQ S/N = 10)
between 37.8 and 55.9 MUg L(-1) . The detection limits obtained in real human
urine samples ranged between 55.2 and 83.6 MUg L(-1) and the quantitation limits
between 196.0 and 276.0 MUg L(-1) . The proposed method has demonstrated its
applicability to the analysis of these local anesthetics in urine samples without
any pretreatment, allowing the rapid determination of these target analytes.
PMID- 26436520
TI - The syndemic of HIV, HIV-related risk and multiple co-morbidities among women who
use drugs in Malaysia: Important targets for intervention.
AB - BACKGROUND: Substance use and HIV are syndemic public health problems in
Malaysia. Harm reduction efforts to reduce HIV transmission have primarily
focused on men with substance use disorders. OBJECTIVES: To explore HIV risk
behaviors, substance use, and social factors associated with poor health outcomes
among women who use drugs in Malaysia. METHODS: A cross-sectional survey of 103
drug-using women in Kuala Lumpur, Malaysia were recruited to assess their
medical, psychiatric and social comorbidity as well as their engagement in
nationally recommended HIV testing and monitoring activities. RESULTS: One-third
reported having ever injected drugs, with most (68.2%) having recently shared
injection paraphernalia. Sex work (44.7%) and infrequent condom use (42.4%) were
common as was underlying psychiatric illness and physical and sexual violence
during childhood and adulthood. Most women (62.1%) had unstable living situations
and suffered from an unmet need for social support and health services. HIV
prevalence was high (20%) with only two thirds of women eligible for
antiretroviral therapy having received it. Suboptimal HIV testing and/or
monitoring was positively associated with interpersonal violence (AOR 2.73; 95%
CI 1.04-7.14) and negatively associated with drug injection (AOR 0.28; 95% CI
0.10-0.77). CONCLUSIONS/IMPORTANCE: Women who use drugs in Malaysia demonstrate
considerable medical, psychiatric and social co-morbidity, which negatively
contributes to optimal and crucial engagement in HIV treatment-as-prevention
strategies. Mental health and social support may be key targets for future public
health interventions aimed at drug-using women in Malaysia.
PMID- 26436522
TI - Keratinocytes and neutrophils are important sources of proinflammatory molecules
in hidradenitis suppurativa.
AB - BACKGROUND: The pathogenesis of the chronic inflammatory skin disease
hidradenitis suppurativa (HS, also known as acne inversa) involves epidermal
alterations such as psoriasiform epidermal hyperplasia and keratin plugging.
Keratinocytes are an important source of proinflammatory molecules in
inflammatory skin diseases and can be stimulated by interleukin (IL)-17(+) cells.
OBJECTIVES: To explore the possible role of the epithelium in the pathogenesis of
HS. METHODS: We performed immunohistochemical stainings and Western blot
experiments to investigate the localization and expression of inflammation
associated molecules, including the cytokine IL-17, components of the
inflammasome including caspase-1, and the endogenous danger-associated molecular
pattern molecules S100A8 and S100A9 (calprotectin). To examine a possible effect
of upregulated proinflammatory cytokines on the inflammatory infiltrate,
differences in the cellular composition of perifollicular and deep dermal
infiltrates were analysed. RESULTS: The number of IL-17(+) cells is increased in
lesional and perilesional HS skin. The epidermis produces proinflammatory
molecules and shows an upregulated expression of components of the NLRP3
inflammasome, activated caspase-1 and expression of S100A8/S100A9. Additionally,
the course of the inflammatory process in HS involves influx of innate immune
cells, particularly IL-17-expressing neutrophils. CONCLUSIONS: IL-17-producing
cells are present in lesional and perilesional HS skin and may contribute to the
initiation of inflammatory processes. Furthermore, the epidermis is a source of
proinflammatory cytokines, shows inflammasome activation and expresses
S100A8/S100A9, thereby possibly contributing to the propagation of inflammation.
A massive influx of IL-17-expressing neutrophils is observed in the deep
infiltrate.
PMID- 26436524
TI - Phase evolution of the two-dimensional Kondo lattice model near half-filling.
AB - Within a mean-field approximation, the ground state and finite temperature phase
diagrams of the two-dimensional Kondo lattice model have been carefully studied
as functions of the Kondo coupling J and the conduction electron concentration
[Formula: see text]. In addition to the conventional hybridization between local
moments and itinerant electrons, a staggered hybridization is proposed to
characterize the interplay between the antiferromagnetism and the Kondo screening
effect. As a result, a heavy fermion antiferromagnetic phase is obtained and
separated from the pure antiferromagnetic ordered phase by a first-order Lifshitz
phase transition, while a continuous phase transition exists between the heavy
fermion antiferromagnetic phase and the Kondo paramagnetic phase. We have
developed an efficient theory to calculate these phase boundaries. As [Formula:
see text] decreases from the half-filling, the region of the heavy fermion
antiferromagnetic phase shrinks and finally disappears at a critical point
[Formula: see text], leaving a first-order critical line between the pure
antiferromagnetic phase and the Kondo paramagnetic phase for [Formula: see text].
At half-filling limit, a finite temperature phase diagram is also determined on
the Kondo coupling and temperature (J-T) plane. Notably, as the temperature is
increased, the region of the heavy fermion antiferromagnetic phase is reduced
continuously, and finally converges to a single point, together with the pure
antiferromagnetic phase and the Kondo paramagnetic phase. The phase diagrams with
such triple point may account for the observed phase transitions in related heavy
fermion materials.
PMID- 26436523
TI - Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral
Fluoroquinolone.
AB - IMPORTANCE: Fluoroquinolones have been associated with collagen degradation,
raising safety concerns related to more serious collagen disorders with use of
these antibiotics, including aortic aneurysm and dissection. OBJECTIVE: To
examine the relationship between fluoroquinolone therapy and the risk of
developing aortic aneurysm and dissection. DESIGN, SETTING, AND PARTICIPANTS: We
conducted a nested case-control analysis of 1477 case patients and 147 700
matched control cases from Taiwan's National Health Insurance Research Database
(NHIRD) from among 1 million individuals longitudinally observed from January
2000 through December 2011. Cases patients were defined as those hospitalized for
aortic aneurysm or dissection. One hundred control patients were matched for each
case based on age and sex. EXPOSURES: Current, past, or any prior-year use of
fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription
within 60 days of the aortic aneurysm or dissection; past use refers to a filled
fluoroquinolone prescription between 61 and 365 days prior to the aortic
aneurysm; and any prior-year use refers to having a fluoroquinolone prescription
filled for 3 or more days any time during the 1-year period before the aortic
aneurysm or dissection. MAIN OUTCOMES AND MEASURES: Risk of developing aortic
aneurysm or dissection. RESULTS: A total of 1477 individuals who experienced
aortic aneurysm or dissection were matched to 147 700 controls. After propensity
score adjustment, current use of fluoroquinolones was found to be associated with
increased risk for aortic aneurysm or dissection (rate ratio [RR], 2.43; 95% CI,
1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI,
1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection
requiring surgery also demonstrated an increased risk associated with current
fluoroquinolone use, but the increase was not statistically significant
(propensity score-adjusted RR, 2.15; 95% CI, 0.97-4.60). CONCLUSIONS AND
RELEVANCE: Use of fluoroquinolones was associated with an increased risk of
aortic aneurysm and dissection. While these were rare events, physicians should
be aware of this possible drug safety risk associated with fluoroquinolone
therapy.
PMID- 26436525
TI - Social influence protects collective decision making from equality bias.
AB - A basic tenet of research on wisdom of the crowds-and key assumption of
Condercet's (1785) Jury Theorem-is the independence of voters' opinions before
votes are aggregated. However, we often look for others' opinions before casting
our vote. Such social influence can push groups toward herding, leading to
"madness of the crowds." To investigate the role of social influence in joint
decision making, in Experiment 1 we had dyads of participants perform a visual
oddball search task together. In the Independent (IND) condition participants
initially made a private decision. If they disagreed, discussion and collective
decision ensued. In the Influence (INF) condition no private decisions were made
and collective decision was immediately negotiated. Dyads that did not accrue
collective benefit under the IND condition improved with added social influence
under the INF condition. In Experiment 2, covertly, we added noise to 1 of the
dyad members' visual search display. The resulting increased heterogeneity in
dyad members' performances impaired the dyadic performance under the IND
condition (Bahrami et al., 2010). Importantly, dyadic performance improved with
social influence under the INF condition, replicating results in Experiment 1.
Further analyses revealed that under the IND condition, dyads exercised equality
bias (Mahmoodi et al., 2015) by granting undue credit to the less-reliable
partner. Under the INF condition, however, the more-reliable partner (correctly)
dominated the joint decisions. Although social influence may impede collective
success under ideal conditions, our results demonstrate how it can help the group
members overcome factors such as equality bias, which could potentially lead to
catastrophic failure. (PsycINFO Database Record
PMID- 26436526
TI - Perceived heaviness in the context of Newton's Second Law: Combined effects of
muscle activity and lifting kinematics.
AB - Researchers generally agree that perceived heaviness is based on the actions
associated with unsupported holding. Psychophysical research has supported this
idea, as has psychophysiological research connecting muscle activity to the
perceptions of heaviness and effort. However, the role of muscle activity in the
context of the resulting motions has not been investigated. In the present study,
perceptions of heaviness were recorded along with the electromyogram (EMG) of the
lifting muscle and peak acceleration of the lift. Consistent with predictions
derived from Newton's Second Law of motion (Force=Mass * Acceleration), normal
and illusory perceptions of heaviness were a function of the ratio of muscle
activity to lifting acceleration. These results identify a psychophysiological
mechanism for heaviness perception based on the forces and motions associated
with unsupported holding.
PMID- 26436527
TI - Task-irrelevant memories rapidly gain attentional control with learning.
AB - Although many of our perceptual biases stem from long-term, repeated exposure,
current theories of visual search assume a central role for visual working memory
(VWM) in guiding attention to target information. Crucially, whether a VWM
representation guides attention depends on the relative priority that the memory
has within VWM. Here, in a combined visual search/VWM task, we used attentional
guidance by irrelevant memories to measure how long a target representation
remains prioritized in VWM when observers repeatedly search for the same target.
Irrelevant memories started guiding attention already when the target was
repeated once, indicating that the target representation rapidly lost priority
within VWM as it moved to long-term memory. By showing that training can lead to
interference from irrelevant memories, the findings resolve a long-standing
paradox on why VWM appears central to, yet at the same time not sufficient nor
necessary for attentional guidance.
PMID- 26436528
TI - High-Performance Small Molecule/Polymer Ternary Organic Solar Cells Based on a
Layer-By-Layer Process.
AB - The layer-by-layer process method, which had been used to fabricate a bilayer or
bulk heterojunction organic solar cell, was developed to fabricate highly
efficient ternary blend solar cells in which small molecules and polymers act as
two donors. The active layer could be formed by incorporating the small molecules
into the polymer based active layer via a layer-by-layer method: the small
molecules were first coated on the surface of poly(3,4-ethylenedioxy
thiophene):poly(styrenesulfonate) ( PEDOT: PSS), and then the mixed solution of
polymer and fullerene derivative was spin-coated on top of a small molecule
layer. In this method, the small molecules in crystalline state were effectively
mixed in the active layer. Without further optimization of the morphology of the
ternary blend, a high power conversion efficiency (PCE) of 8.76% was obtained
with large short-circuit current density (Jsc) (17.24 mA cm(-2)) and fill factor
(FF) (0.696). The high PCE resulted from not only enhanced light harvesting but
also more balanced charge transport by incorporating small molecules.
PMID- 26436529
TI - Surface/Interface Effects on High-Performance Thin-Film All-Solid-State Li-Ion
Batteries.
AB - The further development of all-solid-state batteries is still limited by the
understanding/engineering of the interfaces formed upon cycling. Here, we
correlate the morphological, chemical, and electrical changes of the surface of
thin-film devices with Al negative electrodes. The stable Al-Li-O alloy formed at
the stress-free surface of the electrode causes rapid capacity fade, from 48.0 to
41.5 MUAh/cm(2) in two cycles. Surprisingly, the addition of a Cu capping layer
is insufficient to prevent the device degradation. Nevertheless, Si electrodes
present extremely stable cycling, maintaining >92% of its capacity after 100
cycles, with average Coulombic efficiency of 98%.
PMID- 26436530
TI - Eomesodermin-expressing T-helper cells are essential for chronic
neuroinflammation.
AB - Development of acute experimental autoimmune encephalomyelitis (EAE) depends on
Th17 cells expressing the nuclear factor NR4A2. However, in mice lacking NR4A2 in
T cells, a late-onset disease is still inducible, despite a great reduction in
acute inflammation. We here reveal that development of this late onset disease
depends on cytotoxic T-cell-like CD4(+) T cells expressing the T-box
transcription factor Eomesodermin (Eomes). T-cell-specific deletion of the Eomes
gene remarkably ameliorates the late-onset EAE. Strikingly, similar Eomes(+)
CD4(+) T cells are increased in the peripheral blood and cerebrospinal fluid from
patients in a progressive state of multiple sclerosis. Collective data indicate
an involvement of granzyme B and protease-activated receptor-1 in the
neuroinflammation mediated by Eomes(+) CD4(+) T cells.
PMID- 26436531
TI - Effect of Inducible Co-Stimulatory Molecule siRNA in Cerebral Infarction Rat
Models.
AB - BACKGROUND: T cell-induced inflammatory response and related cytokine secretion
at the injury site may participate in the pathogenesis of cerebral infarction.
Recent studies established inducible co-stimulatory molecule (ICOS) as a novel T
cell-related factor for its activation and functions. We thus investigate the
role of ICOS in cerebral infarction. MATERIAL AND METHODS: The siRNA of ICOS was
first used to suppress the gene expression in cultured lymphocytes. An in vivo
study was then performed by intravenous application of ICOS siRNA in cerebral
infarction rats. Survival rates, neurological scores, serum tumor necrosis factor
(TNF)-alpha, interleukin (IL)-1, and IL-17 levels were observed. RESULTS: The
expression of ICOS in cultured lymphocytes was significantly suppressed by siRNA.
In the in vivo study, the application of siRNA effectively lowered mortality
rates of rats, in addition to the improvement of neurological behaviors and
amelioration of cerebral tissue damage. Serum levels of TNF-alpha, IL-1 and IL-17
were all significantly suppressed after siRNA injection. CONCLUSIONS: ICOS siRNA
can protect brain tissues from ischemia injuries after cerebral infarction,
improve limb movement and coordination, lower the mortality rate of rats, and
inhibit T cell-induced cytokines. These results collectively suggest the
potential treatment efficacy of ICOS siRNA against cerebral infarction.
PMID- 26436533
TI - Adaptive truncated weighting for improving marginal structural model estimation
of treatment effects informally censored by subsequent therapy.
AB - Randomized clinical trials are designed to estimate the direct effect of a
treatment by randomly assigning patients to receive either treatment or control.
However, in some trials, patients who discontinued their initial randomized
treatment are allowed to switch to another treatment. Therefore, the direct
treatment effect of interest may be confounded by subsequent treatment. Moreover,
the decision on whether to initiate a second-line treatment is typically made
based on time-dependent factors that may be affected by prior treatment history.
Due to these time-dependent confounders, traditional time-dependent Cox models
may produce biased estimators of the direct treatment effect. Marginal structural
models (MSMs) have been applied to estimate causal treatment effects even in the
presence of time-dependent confounders. However, the occurrence of extremely
large weights can inflate the variance of the MSM estimators. In this article, we
proposed a new method for estimating weights in MSMs by adaptively truncating the
longitudinal inverse probabilities. This method provides balance in the bias
variance trade-off when large weights are inevitable, without the ad hoc removal
of selected observations. We conducted simulation studies to explore the
performance of different methods by comparing bias, standard deviation,
confidence interval coverage rates, and mean square error under various
scenarios. We also applied these methods to a randomized, open-label, phase III
study of patients with nonsquamous non-small cell lung cancer.
PMID- 26436532
TI - Systematic analysis of somatic mutations impacting gene expression in 12 tumour
types.
AB - We present a novel hierarchical Bayes statistical model, xseq, to systematically
quantify the impact of somatic mutations on expression profiles. We establish the
theoretical framework and robust inference characteristics of the method using
computational benchmarking. We then use xseq to analyse thousands of tumour data
sets available through The Cancer Genome Atlas, to systematically quantify
somatic mutations impacting expression profiles. We identify 30 novel cis-effect
tumour suppressor gene candidates, enriched in loss-of-function mutations and
biallelic inactivation. Analysis of trans-effects of mutations and copy number
alterations with xseq identifies mutations in 150 genes impacting expression
networks, with 89 novel predictions. We reveal two important novel
characteristics of mutation impact on expression: (1) patients harbouring known
driver mutations exhibit different downstream gene expression consequences; (2)
expression patterns for some mutations are stable across tumour types. These
results have critical implications for identification and interpretation of
mutations with consequent impact on transcription in cancer.
PMID- 26436535
TI - In Search of Lost Springs: A Protocol for Locating Active and Inactive Springs.
AB - Groundwater springs are significant landscape features for humans and the biota
that occupies their habitat. Many springs become inactive where groundwater
exploitation by humans has lowered the water table or artesian pressure. In order
to assess this impact, it is important to identify and locate active, and with
more difficulty, inactive springs. Using a variety of archival, environmental and
field-based data, this study presents a protocol for the determination of the
location and status of springs across the Great Artesian Basin of Australia. This
protocol underpins a database of springs, which is not only important for the
assessment of spring ecosystems, but also contributes to understand groundwater
extraction impacts and hydrogeological processes. The database indicates that
30.0% of discharge (artesian) springs in the Great Artesian Basin are entirely
inactive and another 11.8% are partially inactive. For the outcrop (gravity)
springs of the Basin, only 1.9% are entirely inactive and 7.4% partially
inactive, and for the outcrop springs in the Tertiary sandstone overlying the
Basin 30.9% are inactive and 18.2% are partially inactive.
PMID- 26436534
TI - Quantification of Colonic Stem Cell Mutations.
AB - The ability to measure stem cell mutations is a powerful tool to quantify in a
critical cell population if, and to what extent, a chemical can induce mutations
that potentially lead to cancer. The use of an enzymatic assay to quantify stem
cell mutations in the X-linked glucose-6-phosphate dehydrogenase gene has been
previously reported.(1) This method requires the preparation of frozen sections
and incubation of the sectioned tissue with a reaction mixture that yields a blue
color if the cells produce functional glucose-6-phosphate dehydrogenase (G6PD)
enzyme. If not, the cells appear whitish. We have modified the reaction mixture
using Optimal Cutting Temperature Compound (OCT) medium in place of polyvinyl
alcohol. This facilitates pH measurement, increases solubilization of the G6PD
staining components and restricts diffusion of the G6PD enzyme. To demonstrate
that a mutation occurred in a stem cell, the entire crypt must lack G6PD
enzymatic activity. Only if a stem cell harbors a phenotypic G6PD mutation will
all of the progeny in the crypt lack G6PD enzymatic activity. To identify crypts
with a stem cell mutation, four consecutive adjacent frozen sections (a level)
were cut at 7 um thicknesses. This approach of making adjacent cuts provides
conformation that a crypt was fully mutated since the same mutated crypt will be
observed in adjacent sections. Slides with tissue samples that were more than 50
um apart were prepared to assess a total of >10(4) crypts per mouse. The mutation
frequency is the number of observed mutated (white) crypts/by the number of wild
type (blue) crypts in a treatment group.
PMID- 26436536
TI - Interaction of Thermus thermophilus ArsC enzyme and gold nanoparticles naked-eye
assays speciation between As(III) and As(V).
AB - The thermophilic bacterium Thermus thermophilus HB27 encodes chromosomal arsenate
reductase (TtArsC), the enzyme responsible for resistance to the harmful effects
of arsenic. We report on adsorption of TtArsC onto gold nanoparticles for naked
eye monitoring of biomolecular interaction between the enzyme and arsenic
species. Synthesis of hybrid biological-metallic nanoparticles has been
characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV
vis), dynamic light scattering (DLS) and phase modulated infrared reflection
absorption (PM-IRRAS) spectroscopies. Molecular interactions have been monitored
by UV-vis and Fourier transform-surface plasmon resonance (FT-SPR). Due to the
nanoparticles' aggregation on exposure to metal salts, pentavalent and trivalent
arsenic solutions can be clearly distinguished by naked-eye assay, even at 85 MUM
concentration. Moreover, the assay shows partial selectivity against other heavy
metals.
PMID- 26436537
TI - The Battle Hymn of the Tiger Child.
PMID- 26436538
TI - Thinking styles and decision making: A meta-analysis.
AB - This meta-analysis examined whether tendencies to use reflective and intuitive
thinking styles predicted decision performance (normatively correct responding)
and decision experience (e.g., speed, enjoyment) on a range of decision-making
tasks. A pooled sample of 17,704 participants (Mage = 25 years) from 89 samples
produced small but significant weighted average effects for reflection on
performance (r = .11) and experience (r = .14). Intuition was negatively
associated with performance (r = -.09) but positively associated with experience
(r = .06). Moderation analyses using 499 effect sizes revealed heterogeneity
across task-theory match/mismatch, task type, description-based versus experience
based decisions, time pressure, age, and measure type. Effects of both thinking
styles were strongest when the task matched the theoretical strengths of the
thinking style (up to r = .29). Specific tasks that produced the largest thinking
style effects (up to r = .35) were also consistent with system characteristics.
Time pressure weakened the effects of reflection, but not intuition, on
performance. Effect sizes for reflection on performance were largest for
individuals aged either 12 to 18 years or 25+ (up to r = .18), and the effects of
both reflection and intuition on experience were largest for adults aged 25+ (up
to r = .27). Overall, our results indicate that associations between thinking
styles and decision outcomes are context dependent. To improve decision
performance and experience, decision architects and educators should carefully
consider both individual differences in the decision maker and the nature of the
decision task.
PMID- 26436539
TI - Visible-light Induced Reduction of Graphene Oxide Using Plasmonic Nanoparticle.
AB - Present work demonstrates the simple, chemical free, fast, and energy efficient
method to produce reduced graphene oxide (r-GO) solution at RT using visible
light irradiation with plasmonic nanoparticles. The plasmonic nanoparticle is
used to improve the reduction efficiency of GO. It only takes 30 min at RT by
illuminating the solutions with Xe-lamp, the r-GO solutions can be obtained by
completely removing gold nanoparticles through simple centrifugation step. The
spherical gold nanoparticles (AuNPs) as compared to the other nanostructures is
the most suitable plasmonic nanostructure for r-GO preparation. The reduced
graphene oxide prepared using visible light and AuNPs was equally qualitative as
chemically reduced graphene oxide, which was supported by various analytical
techniques such as UV-Vis spectroscopy, Raman spectroscopy, powder XRD and XPS.
The reduced graphene oxide prepared with visible light shows excellent quenching
properties over the fluorescent molecules modified on ssDNA and excellent
fluorescence recovery for target DNA detection. The r-GO prepared by recycled
AuNPs is found to be of same quality with that of chemically reduced r-GO. The
use of visible light with plasmonic nanoparticle demonstrates the good
alternative method for r-GO synthesis.
PMID- 26436540
TI - SubClonal Hierarchy Inference from Somatic Mutations: Automatic Reconstruction of
Cancer Evolutionary Trees from Multi-region Next Generation Sequencing.
AB - Recent improvements in next-generation sequencing of tumor samples and the
ability to identify somatic mutations at low allelic fractions have opened the
way for new approaches to model the evolution of individual cancers. The power
and utility of these models is increased when tumor samples from multiple sites
are sequenced. Temporal ordering of the samples may provide insight into the
etiology of both primary and metastatic lesions and rationalizations for tumor
recurrence and therapeutic failures. Additional insights may be provided by
temporal ordering of evolving subclones--cellular subpopulations with unique
mutational profiles. Current methods for subclone hierarchy inference tightly
couple the problem of temporal ordering with that of estimating the fraction of
cancer cells harboring each mutation. We present a new framework that includes a
rigorous statistical hypothesis test and a collection of tools that make it
possible to decouple these problems, which we believe will enable substantial
progress in the field of subclone hierarchy inference. The methods presented here
can be flexibly combined with methods developed by others addressing either of
these problems. We provide tools to interpret hypothesis test results, which
inform phylogenetic tree construction, and we introduce the first genetic
algorithm designed for this purpose. The utility of our framework is
systematically demonstrated in simulations. For most tested combinations of tumor
purity, sequencing coverage, and tree complexity, good power (>= 0.8) can be
achieved and Type 1 error is well controlled when at least three tumor samples
are available from a patient. Using data from three published multi-region tumor
sequencing studies of (murine) small cell lung cancer, acute myeloid leukemia,
and chronic lymphocytic leukemia, in which the authors reconstructed subclonal
phylogenetic trees by manual expert curation, we show how different
configurations of our tools can identify either a single tree in agreement with
the authors, or a small set of trees, which include the authors' preferred tree.
Our results have implications for improved modeling of tumor evolution and the
importance of multi-region tumor sequencing.
PMID- 26436541
TI - Aptamer Recognition Induced Target-Bridged Strategy for Proteins Detection Based
on Magnetic Chitosan and Silver/Chitosan Nanoparticles Using Surface-Enhanced
Raman Spectroscopy.
AB - Poor selectivity and biocompability remain problems in applying surface-enhanced
Raman spectroscopy (SERS) for direct detection of proteins due to similar spectra
of most proteins and overlapping Raman bands in complex mixtures. To solve these
problems, an aptamer recognition induced target-bridged strategy based on
magnetic chitosan (MCS) and silver/chitosan nanoparticles (Ag@CS NPs) using SERS
was developed for detection of protein benefiting from specific affinity of
aptamers and biocompatibility of chitosan (CS). In this process, one aptamer (or
antibody) modified MCS worked as capture probes through the affinity binding site
of protein. The other aptamer modified Raman report molecules encapsulated Ag@CS
NPs were used as SERS sensing probes based on the other binding site of protein.
The sandwich complexes of aptamer (antibody)/protein/aptamer were separated
easily with a magnet from biological samples, and the concentration of protein
was indirectly reflected by the intensity variation of SERS signal of Raman
report molecules. To explore the universality of the strategy, three different
kinds of proteins including thrombin, platelet derived growth factor BB (PDGF BB)
and immunoglobulin E (lgE) were investigated. The major advantages of this
aptamer recognition induced target-bridged strategy are convenient operation with
a magnet, stable signal expressing resulting from preventing loss of report
molecules with the help of CS shell, and the avoidance of slow diffusion-limited
kinetics problems occurring on a solid substrate. To demonstrate the feasibility
of the proposed strategy, the method was applied to detection of PDGF BB in
clinical samples. The limit of detection (LOD) of PDGF BB was estimated to be 3.2
pg/mL. The results obtained from human serum of healthy persons and cancer
patients using the proposed strategy showed good agreement with that of the ELISA
method but with wider linear range, more convenient operation, and lower cost.
The proposed strategy holds great potential in highly sensitive and selective
analysis of target proteins in complex biological samples.
PMID- 26436542
TI - Effects of renal denervation on renal pelvic contractions and connexin expression
in rats.
AB - AIMS: The renal pelvis shows spontaneous rhythmic contractile activity. We
assessed to what extent this activity depends on renal innervation and studied
the role of connexins in pelvic contractions. METHODS: Rats underwent unilateral
renal denervation or renal transplantation. Renal pelvic pressure and diuresis
were measured in vivo. Spontaneous and agonist-induced contractions of isolated
renal pelves were investigated by wire myography. Rat and human renal pelvic
connexin mRNA abundances and connexin localization were studied by real-time PCR
and immunofluorescence respectively. RESULTS: Renal denervation or
transplantation increased renal pelvic pressure in vivo by about 60 and 150%,
respectively, but did not significantly affect pelvic contraction frequency.
Under in vitro conditions, isolated pelvic preparations from innervated or
denervated kidneys showed spontaneous contractions. Pelves from denervated
kidneys showed about 50% higher contraction frequencies than pelves from
innervated kidneys, whereas contraction force was similar in pelves from
denervated and innervated kidneys. There was no denervation-induced
supersensitivity to noradrenaline or endothelin-1. Renal denervation did not
increase pelvic connexin37, 40, 43 or 45 mRNA abundances. Gap junction blockade
had no effect on spontaneous pelvic contractile activity. CONCLUSIONS: The
denervation-induced effect on pelvic pressure may be the consequence of the
enhanced diuresis. The mechanisms underlying the denervation-induced effects on
pelvic contraction frequency remain unknown. Our data rule out a major role for
two important candidates, by showing that renal denervation neither induced
supersensitivity to contractile agonists nor increased connexin mRNA abundance in
the pelvic wall.
PMID- 26436543
TI - Engineering Proteins for Thermostability with iRDP Web Server.
AB - Engineering protein molecules with desired structure and biological functions has
been an elusive goal. Development of industrially viable proteins with improved
properties such as stability, catalytic activity and altered specificity by
modifying the structure of an existing protein has widely been targeted through
rational protein engineering. Although a range of factors contributing to thermal
stability have been identified and widely researched, the in silico
implementation of these as strategies directed towards enhancement of protein
stability has not yet been explored extensively. A wide range of structural
analysis tools is currently available for in silico protein engineering. However
these tools concentrate on only a limited number of factors or individual protein
structures, resulting in cumbersome and time-consuming analysis. The iRDP web
server presented here provides a unified platform comprising of iCAPS, iStability
and iMutants modules. Each module addresses different facets of effective
rational engineering of proteins aiming towards enhanced stability. While iCAPS
aids in selection of target protein based on factors contributing to structural
stability, iStability uniquely offers in silico implementation of known
thermostabilization strategies in proteins for identification and stability
prediction of potential stabilizing mutation sites. iMutants aims to assess
mutants based on changes in local interaction network and degree of residue
conservation at the mutation sites. Each module was validated using an
extensively diverse dataset. The server is freely accessible at
http://irdp.ncl.res.in and has no login requirements.
PMID- 26436544
TI - Arterial Expression of the Calcium-Sensing Receptor Is Maintained by
Physiological Pulsation and Protects against Calcification.
AB - Vascular calcification (VC) is common in chronic kidney disease (CKD) and
contributes to cardiovascular mortality. The calcium-sensing receptor (CaSR) is
present in human artery, senses extracellular calcium and may directly modulate
VC. OBJECTIVE: to investigate the association between arterial cyclic strain,
CaSR expression and VC. METHODS AND RESULTS: human aortic smooth muscle cells
(HAoSMC) were cultured under static or strained conditions, with exposure to CaSR
agonists, the calcimimetic R568, and after CaSR silencing and over-expression.
High extracellular calcium reduced CaSR expression and promoted osteochondrogenic
transformation and calcium deposition. This was partially prevented by cyclic
strain and exposure to R568. CaSR silencing enhanced calcification and
osteochondrogenic transformation, whereas CaSR over-expression attenuated this
procalcific response, demonstrating a central role for the CaSR in the response
to cyclic strain and regulation of VC. In arterial explants from CKD patients (n
= 11) and controls (n = 9), exposure to R568 did not significantly alter calcium
deposition, osteochondrogenic markers or total artery calcium content.
CONCLUSIONS: physiological mechanical strain is important for arterial
homeostasis and may protect arteries from VC. The beneficial effects of cyclic
strain may be mediated via the CaSR.
PMID- 26436545
TI - Estimating the Sensitivity and Specificity of Real-Time Quantitative PCR of Fecal
Samples for Diagnosis of Rhodococcus equi Pneumonia in Foals.
AB - BACKGROUND: Real-time, quantitative PCR (qPCR) methods for detecting Rhodococcus
equi in feces have been developed as a noninvasive, rapid diagnostic test for R.
equi pneumonia, but have not been evaluated in a large population of foals.
OBJECTIVE: The objective of this study was to evaluate the clinical utility of
fecal PCR as a diagnostic test for R. equi pneumonia in foals using receiver
operating characteristic (ROC) methods. ANIMALS: 186 foals born in 2011 at an R.
equi-endemic ranch in Texas. METHODS: Fecal samples were collected at the time of
onset of clinical signs for pneumonic foals (n = 31). Foals with pneumonia were
matched by age and birth date to healthy (n = 31) and subclinical (n = 124)
control foals; fecal samples were collected from these controls. DNA was
extracted from feces using commercial kits and concentration of virulent R. equi
in feces was determined by qPCR. RESULTS: Concentration of R. equi in feces
differed significantly (P < .05) among groups. The area under the ROC curve for
fecal qPCR for diagnosis of R. equi pneumonia was 89% (95% CI, 83-99), with a
sensitivity of 94% and specificity of 72%. CONCLUSIONS AND CLINICAL IMPORTANCE:
qPCR of feces can be useful as an alternative to tracheobronchial aspiration for
the diagnosis of R. equi in foals with clinical signs of pneumonia. Caution
should be used in extrapolating results of this study to other populations
because fecal concentration of R. equi might vary by geographic location or
management practices.
PMID- 26436546
TI - The Role of Crowding Forces in Juxtaposing beta-Globin Gene Domain Remote
Regulatory Elements in Mouse Erythroid Cells.
AB - The extremely high concentration of macromolecules in a eukaryotic cell nucleus
indicates that the nucleoplasm is a crowded macromolecular solution in which
large objects tend to gather together due to crowding forces. It has been shown
experimentally that crowding forces support the integrity of various nuclear
compartments. However, little is known about their role in control of chromatin
dynamics in vivo. Here, we experimentally addressed the possible role of crowding
forces in spatial organization of the eukaryotic genome. Using the mouse beta
globin domain as a model, we demonstrated that spatial juxtaposition of the
remote regulatory elements of this domain in globin-expressing cells may be lost
and restored by manipulation of the level of macromolecular crowding. In addition
to proving the role of crowding forces in shaping interphase chromatin, our
results suggest that the folding of the chromatin fiber is a major determinant in
juxtaposing remote genomic elements.
PMID- 26436547
TI - Generation of an Enhancer-Trapping Vector for Insertional Mutagenesis in
Zebrafish.
AB - Enhancer trapping (ET) is a powerful approach to establish tissue- or cell
specific reporters and identify expression patterns of uncharacterized genes.
Although a number of enhancer-trapping vectors have been developed and a large
library of fish lines with distinct tissue- or cell-specific expression of
reporter genes have been generated, the specificity and efficiency of trapping
vectors need to be improved because of the bias interaction of minimal promoters
with genomic enhancers. Accordingly, we generated an enhancer-trapping vector
pTME that contains a minimal mouse metallothionein gene (mMTI) promoter upstream
of EGFP reporter. In the first round of screening, twelve zebrafish lines that
carry a single copy of ET cassettes were characterized to have tissue- or cell
specific EGFP expression. One of the highly conserved noncoding elements near an
insertion site of trapping cassettes was characterized as an enhancer that can
specifically regulate the expression of EGFP in cells of the central nervous
system. In addition, the pTME vector contains a mutation-cassette that is able to
effectively block the transcription of an endogenous gene in an ET line with
ubiquitous EGFP expression. Thus, the pTME vector can be used as an alternative
tool for both enhancer trapping and mutagenesis across a target genome.
PMID- 26436548
TI - Involvement of Neuroactive Steroids in Pain, Depression and Anxiety.
AB - Comorbidity between major depressive disorder (MDD), anxiety (generalized
anxiety, panic disorder, social anxiety disorder) and pain is a major
complicating factor in the diagnosis and treatment of psychiatric and
neurological disorders. Although numerous neurotransmitters and/or
neuromodulators may be involved, abnormalities in the GABAergic and glutamatergic
systems seem to be a common factor in all these disorders. Neuroactive steroids
(NASs) have been the object of considerable interest in this area in recent years
since they appear to act predominantly on GABA-A and glutamate NMDA receptors. An
overview of the possible involvement of NASs in MDD, anxiety and pain is provided
in this chapter.
PMID- 26436549
TI - Correction: Visualization of Glutamine Transporter Activities in Living Cells
Using Genetically Encoded Glutamine Sensors.
PMID- 26436550
TI - Is Cryotherapy Friend or Foe for Symptomatic Cervical Ectopy?
AB - OBJECTIVE: To evaluate the success rates and clinical outcomes of cervical
cryotherapy applied to cervical ectopy for symptomatic relief. SUBJECTS AND
METHODS: A total of 124 women who underwent cryotherapy for symptomatic treatment
of cervical ectopy were included in this study. Indications for treatment were:
abundant leucorrhoea (n = 114), post-coital bleeding (n = 22), recurrent
cervicitis (n = 30) and pelvic pain (n = 12). Cryotherapy consisted of the use of
carbon dioxide at -89 degrees C to destroy the ectopic columnar epithelium by
freezing, and it was transmitted to the ectopy through a flat cryoprobe. No
routine anaesthesia or analgesia was administered. All patients were questioned
about the status of their symptoms after 6 weeks of treatment. RESULTS: The
highest success rate was obtained in patients with abundant leucorrhoea (n = 102;
89.5%), while the lowest success rate was achieved in subjects with pelvic pain
(n = 7; 58%). After treatment, no severe complications were observed, except for
hydrorrhoea for a few days. Success rates were 9 times lower in patients who had
3 or more cervicitis episodes per 6 months. CONCLUSION: In this study, the
success rate of cryotherapy was highest in patients with abundant leucorrhoea and
lowest in patients with pelvic pain and recurrent cervicitis. Hence, we recommend
that clinicians perform the procedure in such patients without much delay.
PMID- 26436551
TI - Dynamic Membrane Formation in Anaerobic Dynamic Membrane Bioreactors: Role of
Extracellular Polymeric Substances.
AB - Dynamic membrane (DM) formation in dynamic membrane bioreactors plays an
important role in achieving efficient solid-liquid separation. In order to study
the contribution of extracellular polymeric substances (EPS) to DM formation in
anaerobic dynamic membrane bioreactor (AnDMBR) processes, EPS extraction from and
re-addition to bulk sludge were carried out in short-term filtration tests. DM
formation behaviors could be well simulated by cake filtration model, and sludge
with EPS re-addition showed the highest resistance coefficient, followed by
sludge after EPS extraction. The DM layers exhibited a higher resistance and a
lower porosity for the sludge sample after EPS extraction and for the sludge with
EPS re-addition. Particle size of sludge flocs decreased after EPS extraction,
and changed little with EPS re-addition, which was confirmed by interaction
energy analysis. Further investigations by confocal laser scanning microscopy
(CLSM) analysis and batch tests suggested that the removal of in-situ EPS
stimulated release of soluble EPS, and re-added EPS were present as soluble EPS
rather than bound EPS, which thus improved the formation of DM. The present work
revealed the role of EPS in anaerobic DM formation, and could facilitate the
operation of AnDMBR processes.
PMID- 26436552
TI - Nanoarchitectonics for Dynamic Functional Materials from Atomic-/Molecular-Level
Manipulation to Macroscopic Action.
AB - Objects in all dimensions are subject to translational dynamism and dynamic
mutual interactions, and the ability to exert control over these events is one of
the keys to the synthesis of functional materials. For the development of
materials with truly dynamic functionalities, a paradigm shift from
"nanotechnology" to "nanoarchitectonics" is proposed, with the aim of design and
preparation of functional materials through dynamic harmonization of atomic
/molecular-level manipulation and control, chemical nanofabrication, self
organization, and field-controlled organization. Here, various examples of
dynamic functional materials are presented from the atom/molecular-level to
macroscopic dimensions. These systems, including atomic switches, molecular
machines, molecular shuttles, motional crystals, metal-organic frameworks,
layered assemblies, gels, supramolecular assemblies of biomaterials, DNA origami,
hollow silica capsules, and mesoporous materials, are described according to
their various dynamic functions, which include short-term plasticity, long-term
potentiation, molecular manipulation, switchable catalysis, self-healing
properties, supramolecular chirality, morphological control, drug storage and
release, light-harvesting, mechanochemical transduction, molecular tuning
molecular recognition, hand-operated nanotechnology.
PMID- 26436553
TI - Colonization of Lutzomyia verrucarum and Lutzomyia longipalpis Sand Flies
(Diptera: Psychodidae) by Bartonella bacilliformis, the Etiologic Agent of
Carrion's Disease.
AB - Bartonella bacilliformis is a pathogenic bacterium transmitted to humans
presumably by bites of phlebotomine sand flies, infection with which results in a
bi-phasic syndrome termed Carrion's disease. After constructing a low-passage GFP
labeled strain of B. bacilliformis, we artificially infected Lutzomyia verrucarum
and L. longipalpis populations, and subsequently monitored colonization of sand
flies by fluorescence microscopy. Initially, colonization of the two fly species
was indistinguishable, with bacteria exhibiting a high degree of motility, yet
still confined to the abdominal midgut. After 48 h, B. bacilliformis transitioned
from bacillus-shape to a non-motile, small coccoid form and appeared to be
digested along with the blood meal in both fly species. Differences in
colonization patterns became evident at 72 h when B. bacilliformis was observed
at relatively high density outside the peritrophic membrane in the lumen of the
midgut in L. verrucarum, but colonization of L. longipalpis was limited to the
blood meal within the intra-peritrophic space of the abdominal midgut, and the
majority of bacteria were digested along with the blood meal by day 7. The
viability of B. bacilliformis in L. longipalpis was assessed by artificially
infecting, homogenizing, and plating for determination of colony-forming units in
individual flies over a 13-d time course. Bacteria remained viable at relatively
high density for approximately seven days, suggesting that L. longipalpis could
potentially serve as a vector. The capacity of L. longipalpis to transmit viable
B. bacilliformis from infected to uninfected meals was analyzed via interrupted
feeds. No viable bacteria were retrieved from uninfected blood meals in these
experiments. This study provides significant information toward understanding
colonization of sand flies by B. bacilliformis and also demonstrates the utility
of L. longipalpis as a user-friendly, live-vector model system for studying this
severely neglected tropical disease.
PMID- 26436554
TI - Construction of a Genetic Linkage Map and Identification of QTLs for Seed Weight
and Seed Size Traits in Lentil (Lens culinaris Medik.).
AB - Seed weight and seed size both are quantitative traits and have been considered
as important components of grain yield, thus identification of quantitative trait
loci (QTL) for seed traits in lentil (Lens culinaris) would be beneficial for the
improvement of grain yield. Hence the main objective of this study was to
identify QTLs for seed traits using an intraspecific mapping population derived
from a cross between L. culinaris cv. Precoz (seed weight-5.1g, seed size-5.7mm)
and L. culinaris cv. L830 (seed weight-2.2g, seed size-4mm) comprising 126 F8
RILs. For this, two microsatellite genomic libraries enriched for (GA/CT) and
(GAA/CTT) motif were constructed which resulted in the development of 501 new
genomic SSR markers. Six hundred forty seven SSR markers (including 146
previously published) were screened for parental polymorphism and 219 (33.8%)
were found to be polymorphic among the parents. Of these 216 were mapped on seven
linkage groups at LOD4.0 spanning 1183.7cM with an average marker density of
5.48cM. Phenotypic data from the RILs was used to identify QTLs for the seed
weight and seed size traits by single marker analysis (SMA) followed by composite
interval mapping (CIM) which resulted in one QTL each for the 2 traits (qSW and
qSS) that were co-localized on LG4 and explained 48.4% and 27.5% of phenotypic
variance respectively. The current study would serve as a strong foundation for
further validation and fine mapping for utilization in lentil breeding programs.
PMID- 26436555
TI - Maternal Lineage of Warmblood Mares Contributes to Variation of Gestation Length
and Bias of Foal Sex Ratio.
AB - Maternal lineage influences performance traits in horses. This is probably caused
by differences in mitochondrial DNA (mtDNA) transferred to the offspring via the
oocyte. In the present study, we investigated if reproductive traits with high
variability-gestation length and fetal sex ratio-are influenced by maternal
lineage. Data from 142 Warmblood mares from the Brandenburg State Stud at
Neustadt (Dosse), Germany, were available for the study. Mares were grouped
according to their maternal lineage. Influences on the reproduction parameters
gestation length and sex ratio of offspring were analyzed by simple and multiple
analyses of variance. A total of 786 cases were included. From the 142 mares, 119
were assigned to six maternal lineages with n>=10 mares per lineage, and 23 mares
belonged to smaller maternal lineages. The mean number of live foals produced per
mare was 4.6+/-3.6 (+/-SD). Live foal rate was 83.5%. Mean gestation length was
338.5+/-8.9 days (+/-SD) with a range of 313 to 370 days. Gestation length was
affected by maternal lineage (p<0.001). Gestation length was also significantly
influenced by the individual mare, age of the mare, year of breeding, month of
breeding and sex of the foal (p<0.05). Of the 640 foals born alive at term, 48%
were male and 52% female. Mare age group and maternal lineage significantly
influenced the sex ratio of the foals (p<0.05). It is concluded that maternal
lineage influences reproductive parameters with high variation such as gestation
length and foal sex ratio in horses. In young primiparous and aged mares, the
percentage of female offspring is higher than the expected 1:1 ratio.
PMID- 26436556
TI - Emerging treatments for recurrent prostate cancer.
AB - Despite radical treatment, many men with prostate cancer will develop recurrence
of their disease. In an exciting era of new therapies for prostate cancer in
general, we focus on how these will specifically benefit those men with recurrent
disease. We consider salvage treatments aimed at those with local recurrence
confined to the prostate gland, therapies for those presenting with metastatic
recurrence and the approach to men presenting with a rising prostate-specific
antigen but no demonstrable disease (M0). In general, men with recurrent disease
are often under-represented in randomized clinical trials. Consequently, evidence
to guide treatment for these men is often lacking and this needs to be addressed
in order to improve and better define our approach to this problem in the future.
PMID- 26436557
TI - Products and Mechanism of the Reaction of 1-Pentadecene with NO3 Radicals and the
Effect of a -ONO2 Group on Alkoxy Radical Decomposition.
AB - The linear C15 alkene, 1-pentadecene, was reacted with NO3 radicals in a Teflon
environmental chamber and yields of secondary organic aerosol (SOA) and
particulate beta-hydroxynitrates, beta-carbonylnitrates, and organic peroxides
(beta-nitrooxyhydroperoxides + dinitrooxyperoxides) were quantified using a
variety of methods. Reaction occurs almost solely by addition of NO3 to the C?C
double bond and measured yields of beta-hydroxynitrate isomers indicate that 92%
of addition occurs at the terminal carbon. Molar yields of reaction products
determined from measurements, a proposed reaction mechanism, and mass-balance
considerations were 0.065 for beta-hydroxynitrates (0.060 and 0.005 for 1
nitrooxy-2-hydroxypentadecane and 1-hydroxy-2-nitrooxypentadecane isomers), 0.102
for beta-carbonylnitrates, 0.017 for organic peroxides, 0.232 for beta
nitrooxyalkoxy radical isomerization products, and 0.584 for tetradecanal and
formaldehyde, the volatile C14 and C1 products of beta-nitrooxyalkoxy radical
decomposition. Branching ratios for decomposition and isomerization of beta
nitrooxyalkoxy radicals were 0.716 and 0.284 and should be similar for other
linear 1-alkenes >= C6 whose alkyl chains are long enough to allow for
isomerization to occur. These branching ratios have not been measured previously,
and they differ significantly from those estimated using structure-activity
relationships, which predict >99% isomerization. It appears that the presence of
a -ONO2 group adjacent to an alkoxy radical site greatly enhances the rate of
decomposition relative to isomerization, which is otherwise negligible, and that
the effect is similar to that of a -OH group. The results provide insight into
the effects of molecular structure on mechanisms of oxidation of volatile organic
compounds and should be useful for improving structure-activity relationships
that are widely used to predict the fate of these compounds in the atmosphere and
for modeling SOA formation and aging.
PMID- 26436558
TI - Skin Necrosis and Purpura Fulminans in Children With and Without Thrombophilia--A
Tertiary Center's Experience.
AB - Purpura fulminans (PF) is a very rare clinicopathologic skin disorder comprising
dermal microvascular thrombosis associated with perivascular hemorrhage of
multiple origins. It may occur as the presenting symptom of severe congenital
deficiency of protein C (PC) or protein S (PS) during the newborn period, or
later in life following oral anticoagulant therapy with vitamin K antagonists, or
of sepsis that may be associated with disseminated intravascular coagulation.
Treatment consists of anticoagulants and PC concentrates during acute episodes.
We report our experience in the diagnosis and management of pediatric PF. The
medical records of the 6 children aged 2-16 years (median: 5 years) who presented
with PF to our tertiary care center between 1996 and 2013 were studied. The
thrombophilia workup revealed either the presence of congenital homozygous PC
deficiency, prothrombotic polymorphisms (factor V Leiden and FIIG20210A
heterozygosity), acquired PC/PS deficiency, or no discernible thrombophilia. The
skin necrosis resolved following conservative fresh-frozen plasma/anticoagulant
therapy in 2 cases, whereas 3 children required interventional plastic surgery.
The sixth case, a 10-year-old child with severe PC deficiency, heterozygous
factor V Leiden, and FIIG20210A, received recombinant activated PC. PF in
childhood is rare and has multiple etiologies. Understanding of the variable
pathogenesis and risk factors will facilitate diagnosis and appropriate clinical
management.
PMID- 26436559
TI - Effect of Splinting on Dimensional Accuracy of Impressions Made of Implants with
Different Subgingival Alignments.
AB - PURPOSE: Placement of implants at deeper levels of gingiva is sometimes
inevitable because of issues like esthetics or bone availability. The accuracy of
impressions may be affected in these situations. The aim of this in vitro study
was to evaluate the effects of splinting and length of impression copings on the
accuracy of impressions made of deeply placed implants. MATERIALS AND METHODS: A
metal model with two parallel implants (Implantium; Dentium) was fabricated. One
hundred and twenty impressions were made using the direct impression technique
with and without splinting the impression copings (using short and long
impression copings). Impressions were made of implants at three subgingival
levels (1, 3, and 6 mm) using regular viscosity poly(vinyl siloxane). The
impressions were poured with type IV dental stone. Displacements in the x, y, and
z axes, as well as rotational discrepancies and interimplant distances were
measured with a coordinate measuring machine. Data were analyzed with Kruskal
Wallis, Mann-Whitney, and nonparametric adjusted rank transform tests. RESULTS:
There was less rotational displacement using longer impression copings at
different subgingival positions of the implants, either with splinted or
nonsplinted direct technique (p < 0.05). Also, the nonsplinted technique produced
more accurate impressions at different apico-coronal levels of implants than the
splinted technique using short impression copings (p < 0.05). CONCLUSIONS:
According to the findings of this study, longer impression copings yielded better
results than shorter ones in both splinted and nonsplinted techniques. Also,
nonsplinted short impression copings produced more accurate impressions than
splinted short impression copings.
PMID- 26436561
TI - Photoelectron Spectroscopy of BiAu(-) and BiBO(-): Further Evidence of the
Analogy between Au and Boronyl.
AB - Boronyl (BO) is a monovalent sigma radical with a B=O triple bond. Its chemistry
has remained relatively unknown, though analogy has been established for BO with
monovalent atoms, such as H or Au. Here we report a photoelectron spectroscopic
study of BiAu(-) and BiBO(-), showing further evidence of the analogy between Au
and BO. The photoelectron spectra of BiAu(-) and BiBO(-) are found to be similar,
suggesting that they possess similar electronic structure and chemical bonding.
The electron affinities of BiAu and BiBO are measured to be 1.38(4) and 1.84(3)
eV, respectively. The ground states of both BiAu and BiBO are shown to be a
triplet (X (3)Sigma(-)). In addition, vibrational structures are resolved in the
spectra of BiBO(-). Two vibrational frequencies at 320(30) and 1860(50) cm(-1)
are measured for the ground state of BiBO, corresponding to the Bi-B and B-O
stretching modes, respectively. The low-lying electronic excited states of BiAu
and BiBO are also found to be similar: their first four excited states are A
(1)Delta, B (1)Sigma(+), C (3)Pi, and D (1)Pi, with excitation energies at 0.71,
1.29, 2.54, and 2.67 eV for BiAu and 0.63, 1.26, 3.68, and 3.82 eV for BiBO,
respectively, above the (3)Sigma(-) ground state. Weak photoelectron features
related to two-electron detachment transitions are also observed for both anions
because of strong electron correlation effects in the ground state of the anions.
PMID- 26436560
TI - Zinc pyrithione inhibits caspase-3 activity, promotes ErbB1-ErbB2
heterodimerization and suppresses ErbB2 downregulation in cardiomyocytes
subjected to ischemia/reperfusion.
AB - Heart tissue becomes zinc-depleted and the capacity to mobilize labile zinc is
diminished, indicating zinc dyshomeostasis during ischemia/reperfusion (I/R).
Apparently, zinc pyrithione restores the basal zinc levels during I/R and
prevents apoptosis by activating phosphatidyl inositol-3-kinase/Akt and targeting
mitochondrial permeability transition. Receptor tyrosine kinases of the ErbB
family (ErbB1 to ErbB4) are cell surface proteins that can regulate cell growth,
proliferation and survival. Previous studies have shown that zinc pyrithione
induced activation of PI3kinase/Akt requires ErbB2 expression. On the other hand,
while I/R decreases ErbB2 levels causing cardiomyocyte dysfunction and cell
death, zinc pyrithione restores ErbB2 levels and maintains cardiomyocyte
function. H9c2 cells expressed all the four ErbBs, although the expression of
ErbB1 and ErbB2 were higher compared to ErbB3 and ErbB4. Hypoxia/Reoxygenation
(H/R) had opposing effects on the mRNA expression of ErbB1 and ErbB2. ErbB2 mRNA
levels were enhanced, but corresponding ErbB2 protein levels decreased after
reoxygenation. H/R induced the degradation of ErbB2 in caspase-3 dependent
manner, with the formation of a 25kDa fragment. This fragment could be detected
after H/R only upon treatment of the cells with a proteasomal inhibitor, ALLN,
suggesting that caspase-mediated cleavage of 185kDa ErbB2 results in C-terminal
cleavage and formation of 25kDa fragment, which is further degraded by
proteasome. Heterodimerization and phosphorylation of ErbB2/ErbB1 which decreased
upon reoxygenation, was promoted by zinc pyrithione. Zinc pyrithione effectively
suppressed the caspase activation, decreased the proteolytic cleavage of ErbB2,
enhanced the phosphorylation and activation of ErbB1-ErbB2 complexes and improved
the cell survival after hypoxia/reoxygenation.
PMID- 26436562
TI - Nicotine intake and problem solving strategies are modified during a cognitively
demanding water maze task in rats.
AB - BACKGROUND: Nicotine is the major addictive component in tobacco, and despite
well-established adverse health effects of tobacco addiction, some smokers have
difficulty quitting. The acute cognitive enhancement and/or the amelioration of
the cognitive disruption during withdrawal that some smokers experience after
smoking are among important factors that hinder quit attempts. The animal model
presented in the current study is comparable to the human smoking condition
although nicotine intake routes are different. Rats were exposed to a free choice
of oral nicotine starting at adolescence, and given a water maze (WM) task as
adults. This design allowed us to see if rats alter their nicotine intake during
the WM task and if nicotine preference and intake modify abilities and strategies
rats use for problem solving. METHODS: Male and female rats were exposed to a
free choice of oral nicotine/water for 24weeks, starting at five weeks of age.
After this period, they were selected based on their nicotine intake and,
together with control animals that received only water, were subjected to a place
learning task in the WM. Free-choice nicotine exposure continued during WM
testing. Following acquisition, the probe trial presented the rats with a choice
between using two different strategies for problem solving. RESULTS: Nicotine
supported acquisition and rats increased their nicotine intake during WM testing;
this effect was more pronounced in male rats with minimum nicotine preference and
intake. Furthermore, nicotine modified the "female type" strategy in solving the
place-learning task and nicotine treated female rats, unlike control females,
behaved like males. CONCLUSIONS: The increase in nicotine intake during mental
engagement, and the sexually dimorphic effect of nicotine on problem solving
strategies that we have observed in rats, may suggest that implementing sex
specific smoking cessation approaches, especially under stressful and cognitively
demanding conditions, may be useful in helping smokers quit.
PMID- 26436563
TI - Electrical detection of magnetic skyrmions by tunnelling non-collinear
magnetoresistance.
AB - Magnetic skyrmions are localized non-collinear spin textures with a high
potential for future spintronic applications. Skyrmion phases have been
discovered in a number of materials and a focus of current research is to
prepare, detect and manipulate individual skyrmions for implementation in
devices. The local experimental characterization of skyrmions has been performed
by, for example, Lorentz microscopy or atomic-scale tunnel magnetoresistance
measurements using spin-polarized scanning tunnelling microscopy. Here we report
a drastic change of the differential tunnel conductance for magnetic skyrmions
that arises from their non-collinearity: mixing between the spin channels locally
alters the electronic structure, which makes a skyrmion electronically distinct
from its ferromagnetic environment. We propose this tunnelling non-collinear
magnetoresistance as a reliable all-electrical detection scheme for skyrmions
with an easy implementation into device architectures.
PMID- 26436564
TI - Skyrmions: Detection with unpolarized currents.
PMID- 26436566
TI - Heterogeneous sub-continuum ionic transport in statistically isolated graphene
nanopores.
AB - Graphene and other two-dimensional materials offer a new class of ultrathin
membranes that can have atomically defined nanopores with diameters approaching
those of hydrated ions. These nanopores have the smallest possible pore volumes
of any ion channel, which, due to ionic dehydration and electrokinetic effects,
places them in a novel transport regime and allows membranes to be created that
combine selective ionic transport with ultimate permeance and could lead to
separations and sensing applications. However, experimental characterization and
understanding of sub-continuum ionic transport in nanopores below 2 nm is
limited. Here we show that isolated sub-2 nm pores in graphene exhibit, in
contrast to larger pores, diverse transport behaviours consistent with ion
transport over a free-energy barrier arising from ion dehydration and
electrostatic interactions. Current-voltage measurements reveal that the
conductance of graphene nanopores spans three orders of magnitude and that they
display distinct linear, voltage-activated or rectified current-voltage
characteristics and different cation-selectivity profiles. In rare cases, rapid,
voltage-dependent stochastic switching is observed, consistent with the presence
of a dissociable group in the pore vicinity. A modified Nernst-Planck model
incorporating ion hydration and electrostatic effects quantitatively matches the
observed behaviours.
PMID- 26436565
TI - Picosecond photoresponse in van der Waals heterostructures.
AB - Two-dimensional crystals such as graphene and transition-metal dichalcogenides
demonstrate a range of unique and complementary optoelectronic properties.
Assembling different two-dimensional materials in vertical heterostructures
enables the combination of these properties in one device, thus creating
multifunctional optoelectronic systems with superior performance. Here, we
demonstrate that graphene/WSe2/graphene heterostructures ally the high
photodetection efficiency of transition-metal dichalcogenides with a picosecond
photoresponse comparable to that of graphene, thereby optimizing both speed and
efficiency in a single photodetector. We follow the extraction of photoexcited
carriers in these devices using time-resolved photocurrent measurements and
demonstrate a photoresponse time as short as 5.5 ps, which we tune by applying a
bias and by varying the transition-metal dichalcogenide layer thickness. Our
study provides direct insight into the physical processes governing the detection
speed and quantum efficiency of these van der Waals heterostuctures, such as out
of-plane carrier drift and recombination. The observation and understanding of
ultrafast and efficient photodetection demonstrate the potential of hybrid
transition-metal dichalcogenide-based heterostructures as a platform for future
optoelectronic devices.
PMID- 26436567
TI - Complete mitochondrial genome of Drabescoides nuchalis (Hemiptera: Cicadellidae).
AB - The complete mitochondrial genome (mitogenome) of Drabescoides nuchalis
(Hemiptera: Cicadellidae) was sequenced. It is 15 309 bp in length with 75.62% (A
+ T) content and comprises 13 protein-coding genes, 22 transfer RNAs, two
ribosomal RNA genes, and a non-coding region (GenBank accession no. KR349344).
Gene order is identical to that of the inferred ancestral insect genome. All PCGs
start with an ATN codon and terminate with TAA except ND4, which has an
incomplete stop codon (T). The anticodons are identical to those of Drosophila
yakuba. The phylogenetic tree confirms D. nuchalis and two Cicadellidae species
are clustered into a clade, and Cicadellidae is a monophyletic group and provides
support for the sister relationship of leafhopper and treehopper.
PMID- 26436568
TI - Interventions at the laboratory level to reduce laboratory test ordering by
family physicians: Systematic review.
AB - OBJECTIVES: To assess the effectiveness of interventions by laboratories and to
increase rational and reduce unnecessary family physician test ordering. DESIGN
AND METHODS: MEDLINE [1946-present], EMBASE [1980-present], EBM Reviews [1991
present](Cochrane Database of Systematic Reviews, ACP Journal Club, Database of
Abstracts of Reviews of Effects, - Cochrane Central Register of Controlled
Trials, Cochrane Methodology Register, Health Technology Assessment, NHS Economic
Evaluation Database), PubMed [1966-present], PubMed Central [1900-present],
Scopus [1960-present], Web of Science [1900-present] and CINAHL [1982-present]
were searched with no language or publication limits. Non-randomised studies were
assessed with the Newcastle-Ottawa scale. RESULTS: The search identified 9282
titles and abstracts, 238 were read in full-text and 3 cohort and 7 before- and
after-studies were included. Most focused on changing a few tests and evaluated
the interventions over several months. Seven changed laboratory forms (the two
largest involved 5.2 million and 3.2 million tests), one negotiated a test
ordering protocol with family physicians, and two required laboratory approval.
They achieved an average 35% reduction in the 19 targeted tests, with a wide
range (0%-100% reduction). CONCLUSIONS: Ten studies were identified which tested
interventions by laboratories to reduce test ordering by family physicians, and
achieved an average 35% reduction in the 19 targeted tests. The rationale for
choosing specific tests for intervention was often not explained, most studies
targeted a few tests for several months, the tests and test volumes differed
widely across studies, no author improved the results of previous interventions
or asked participants their opinions about the intervention or assessed factors
impeding change.
PMID- 26436569
TI - Different forms of Hb Le Lamentin. An unexpected finding in Hba1c quantification.
AB - OBJECTIVES: Glycated hemoglobin (HbA1c) is accepted as the most trusted marker
for monitoring patients with diabetes mellitus. Ion-exchange high-performance
liquid chromatography (HPLC) is one of the most widely used methods for HbA1c
analysis. The presence of a hemoglobin variant can interfere with HbA1c
quantification, requiring other analyses to clarify the results.Herein, we
present two cases of Hb Le Lamentin, which, although they were the same variant,
were thought to correspond to different hemoglobinopathies because of their
percentages. DESIGN AND METHODS: Two male patients presented with an anomalous
peak between HbA1c and HbA0 during a routine analysis of HbA1c using ion-exchange
HPLC (VariantTM II Turbo).The hemoglobin variants were studied using capillary
zone electrophoresis with the Sebia system, and the globin chains were analyzed
by reverse-phase HPLC. A genetic analysis was performed using automated
sequencing of the alpha2 and beta genes. RESULTS: In this work, we describe the
first case of homozygous Hb Le Lamentin and the first double-heterozygous case of
Hb Le Lamentin/Hb City of Hope. CONCLUSIONS: Although the presence of these
variants does not lead to clinical anomalies, it also does not affect hematologic
parameters. The variants have an impact on the determination of glycated
hemoglobin levels using ion-exchange HPLC because the retention time interferes
with the elution time of HbA1c, resulting in a falsely reduced value. Therefore,
it is necessary to either recalculate the result or use another measurement
method.
PMID- 26436570
TI - Polymorphisms rs144723656, rs2268574, and rs2268575 of the glucokinase gene are
not associated with obese women with type 2 diabetes mellitus.
PMID- 26436571
TI - Oncolytic Newcastle disease virus as a prospective anti-cancer therapy. A
biologic agent with potential to break therapy resistance.
AB - INTRODUCTION: Oncolytic viruses (OVs) selectively replicate in tumor cells and
cause cancer cell death. Most OVs in clinical studies are genetically engineered.
In contrast, the avian Newcastle disease virus (NDV) is a naturally oncolytic RNA
virus. While anti-viral immunity is considered a major problem in achieving
maximal tumor cell killing by OVs, this review discusses the importance of NDV
immunogenic cell death (ICD) and how anti-viral immune responses can be
integrated to induce maximal post-oncolytic T-cell-mediated anti-tumor immunity.
Since replication of NDV is independent of host cell DNA replication (which is
the target of many cytostatic drugs and radiotherapy) and because of other
findings, oncolytic NDV is a candidate agent to break therapy resistance of tumor
cells. AREAS COVERED: Properties of this avian paramyxovirus are summarized with
special emphasis to its anti-neoplastic and immune-stimulatory properties. The
review then discusses prospective anti-cancer therapies, including treatments
with NDV alone, and combinations with an autologous NDV-modified tumor cell
vaccine or with a viral oncolysate pulsed dendritic cell vaccine. Various
combinatorial approaches between these and with other modalities are also
reviewed. EXPERT OPINION: Post-oncolytic anti-tumor immunity based on ICD is in
the expert's opinion of greater importance for long-term therapeutic effects than
maximal tumor cell killing. Of the various combinatorial approaches discussed,
the most promising and feasible for clinical practice appears to be the
combination of systemic NDV pre-treatment with anti-tumor vaccination.
PMID- 26436573
TI - Addendum.
PMID- 26436572
TI - Hepatocyte nuclear factor-alpha genetic mutation in a Chinese pedigree with
maturity-onset diabetes of the young (MODY3).
PMID- 26436574
TI - Fluorine-controlled C-H borylation of arenes catalyzed by a PSiN-pincer platinum
complex.
AB - An efficient, regioselective synthesis of fluorine-substituted arylboronic esters
was achieved through fluorine-controlled C-H borylation of arenes with diboron
catalyzed by a PSiN-platinum complex. The promising utility of the PSiN-platinum
catalyst and its unique regioselectivity were demonstrated for the first time,
which would complement the well-developed Ir-catalyzed C-H borylation.
PMID- 26436575
TI - Orthogonal gene knockout and activation with a catalytically active Cas9
nuclease.
AB - We have developed a CRISPR-based method that uses catalytically active Cas9 and
distinct single guide (sgRNA) constructs to knock out and activate different
genes in the same cell. These sgRNAs, with 14- to 15-bp target sequences and MS2
binding loops, can activate gene expression using an active Streptococcus
pyogenes Cas9 nuclease, without inducing double-stranded breaks. We use these
'dead RNAs' to perform orthogonal gene knockout and transcriptional activation in
human cells.
PMID- 26436576
TI - Simple Bulk Readout of Digital Nucleic Acid Quantification Assays.
AB - Digital assays are powerful methods that enable detection of rare cells and
counting of individual nucleic acid molecules. However, digital assays are still
not routinely applied, due to the cost and specific equipment associated with
commercially available methods. Here we present a simplified method for readout
of digital droplet assays using a conventional real-time PCR instrument to
measure bulk fluorescence of droplet-based digital assays. We characterize the
performance of the bulk readout assay using synthetic droplet mixtures and a
droplet digital multiple displacement amplification (MDA) assay. Quantitative MDA
particularly benefits from a digital reaction format, but our new method applies
to any digital assay. For established digital assay protocols such as digital
PCR, this method serves to speed up and simplify assay readout. Our bulk readout
methodology brings the advantages of partitioned assays without the need for
specialized readout instrumentation. The principal limitations of the bulk
readout methodology are reduced dynamic range compared with droplet-counting
platforms and the need for a standard sample, although the requirements for this
standard are less demanding than for a conventional real-time experiment.
Quantitative whole genome amplification (WGA) is used to test for contaminants in
WGA reactions and is the most sensitive way to detect the presence of DNA
fragments with unknown sequences, giving the method great promise in diverse
application areas including pharmaceutical quality control and astrobiology.
PMID- 26436577
TI - Helium Ion Microscopy Visualizes Lipid Nanodomains in Mammalian Cells.
AB - Cell membranes are composed of 2D bilayers of amphipathic lipids, which allow a
lateral movement of the respective membrane components. These components are
arranged in an inhomogeneous manner as transient micro- and nanodomains, which
are believed to be crucially involved in the regulation of signal transduction
pathways in mammalian cells. Because of their small size (diameter 10-200 nm),
membrane nanodomains cannot be directly imaged using conventional light
microscopy. Here, direct visualization of cell membrane nanodomains by helium ion
microscopy (HIM) is presented. It is shown that HIM is capable to image
biological specimens without any conductive coating and that HIM images clearly
allow the identification of nanodomains in the ultrastructure of membranes with
1.5 nm resolution. The shape of these nanodomains is preserved by fixation of the
surrounding unsaturated fatty acids while saturated fatty acids inside the
nanodomains are selectively removed. Atomic force microscopy, fluorescence
microscopy, 3D structured illumination microscopy, and direct stochastic optical
reconstruction microscopy provide additional evidence that the structures in the
HIM images of cell membranes originate from membrane nanodomains. The nanodomains
observed by HIM have an average diameter of 20 nm and are densely arranged with a
minimal nearest neighbor distance of ~ 15 nm.
PMID- 26436578
TI - Mentalization in borderline personality disorder: From bench to bedside.
AB - The current special issue focuses on the potential of mentalizing as a
translational construct for the understanding and treatment of borderline
personality disorder (BPD). Mentalizing, which provides the central construct
around which mentalization-based therapy (MBT) and theory is organized, refers to
the capacity to meaningfully reflect on the mind of others as well as the self.
In this introductory article to the special issue, we begin by discussing the
need for and nature of translational research. We contend that translational
research in mental health and personality disorder, in particular, lags behind
that of other medical disorders because of the challenges inherent in meeting
translational criteria. We discuss these criteria and we demonstrate the
potential of the construct of mentalizing to meet translational criteria in the
context of BPD. This article thereby provides the context for the other 3 papers
in this special issue which each represent a different point along the
translational spectrum. In all, our aim is to provide a foundation for the
further evaluation of the usefulness and potential of mentalizing as
translational construct in the context of BPD.
PMID- 26436579
TI - The mind in the making: Developmental and neurobiological origins of mentalizing.
AB - Tracing the development of mentalizing is central to understanding how we come to
learn about the mind. Barring significant biological or developmental
abnormalities, we all come to form an understanding of the mind and mental
states. But how does this happen, and what accounts for individual differences in
abilities to reason about mental states (i.e., desires, feelings, intentions)?
The first section of the present article brings together relevant developmental
research to outline the normative developmental trajectory of mentalizing. The
second section delves into attachment research to drive home the point that this
fundamental human capacity develops in tandem with early attachment
relationships, and underscores the fact that suboptimal attachment contexts can
hinder the developmental progression of mentalizing. Biobehavioral mechanisms
that have been proposed to mediate this developmental process are discussed in
the third section, with a particular focus on the neuropeptide oxytocin.
PMID- 26436580
TI - The neurobiology of mentalizing.
AB - Mentalizing is the capacity to understand ourselves and others in terms of
intentional mental states, such as feelings, desires, wishes, attitudes, and
goals. It is a fundamental capacity in our complex social environment. This
article reviews our current understanding of the neurobiology of mentalizing. We
first summarize the key assumptions of the mentalizing approach to normal and
disrupted development. This is followed by discussion of the multiple dimensions
of mentalizing and our emerging knowledge of the neural circuits that underlie
these dimensions. We then consider the neurobiology of attachment and arousal
regulation in relation to mentalizing, and summarize relevant studies in this
area. Finally, we discuss the limitations of extant research and outline
implications for future research.
PMID- 26436581
TI - Translation: Mentalizing as treatment target in borderline personality disorder.
AB - The role of mentalizing in relation to borderline personality disorder (BPD) is
examined with a view to achieving improved levels of mentalizing in BPD patients
as a therapeutic target. The article seeks to explain why mentalizing works as a
treatment target for BPD, and suggests that a mentalizing approach to BPD may be
at the core of any successful intervention.
PMID- 26436582
TI - Mentalization as a common process in treatments for borderline personality
disorder: Commentary on the special issue on mentalization in borderline
personality disorder.
AB - Chapman and Dixon-Gordon were invited to write this commentary, they were
concerned that they did not know enough about mentalization to make coherent
comments on this interesting series. As it turns out, they were among a shrinking
minority, as the past decade has witnessed a surge research on mentalization.
Work in this field has been pioneered, in no small part, by the authors of the
present issue. Collectively, this set of articles provides a useful summary of
the state of mentalization research for the uninitiated and makes a compelling
case for mentalization as a key translational construct, particularly with regard
to borderline personality disorder (BPD). Mentalization deserves attention in
further translational research as well as in treatment refinement for BPD and
other clinical problems. Future work should also involve the development of
effective, objective ways to assess mentalization. Ultimately, the use of
translational constructs to loosen the boundaries between evidence-based
treatment approaches may help us move toward more refined, accessible, and
effective treatment for BPD and other complex mental health problems.
PMID- 26436583
TI - Bringing research findings to the clinic and back: Commentary on the special
issue on mentalization in borderline personality disorder.
AB - The articles assembled in this special issue demonstrate the broadening
acceptance that a failure of "mentalization" is central in borderline personality
disorder (BPD). This idea has emerged from a number of places, from astute
clinicians who recognized that individuals with BPD were often limited in their
ability to recognize and describe their own emotions to empirical work on emotion
recognition in BPD. These articles provide a compelling argument that
mentalization, with its relatively distinct and testable cognitive components, is
a fertile ground for translational research. They also suggest a pathway by which
empirical studies can illuminate clinical understanding. To highlight this point,
it is now the routine to explain the laboratory evidence for deficits in
emotional interoception to patients with BPD. This has been useful in helping to
explain the internal and nuanced nature of patients' difficulties (apparent in
laboratory testing but not obvious in casual encounters. This translational
discussion with patients maps very closely onto an approach the editors argue for
in this special issue.
PMID- 26436584
TI - A framework for all seasons: Commentary on the special issue on mentalization in
borderline personality disorder.
AB - It is interesting to consider whether impairment in the capacity to mentalize
might be a persuasive way to describe the core pathology in most patients with a
personality disorder (PD). It has long been recognized that a dimensional
approach to understanding PDs is more useful than the traditional categorical
diagnostic model. Studies are pointing to an underlying general factor as a
latent dimension of borderline personality disorder (BPD), perhaps reflecting
shared or common genetic endophenotypes as risk factors for the development of
BPD or other PDs. With regard to the focus on mentalizing in particular, however
one thinks about impairment in mentalizing as a core reflection of personality
pathology, it is helpful to drill down to deeper levels. In these pages, the
authors do a remarkable job of unpacking, to the granular level, the many
components of mentalization and the attachment process.
PMID- 26436585
TI - Vulnerabilities of the mentalization-based models of vulnerability: A rejoinder
to commentaries on the special issue on mentalization in borderline personality
disorder.
AB - Fonagy and Sharp read the commentaries with interest, respect, and deep
gratitude. Interest, because, consistent with their mentalization-based approach,
they discover most about themselves through the eyes of others. Respect, because
all the commentators are major contributors to the field whose contributions
deserve special issues in their own right. And finally, deep gratitude for the
time and effort they took to review our contributions with thoughtfulness and
insight. Fonagy and Sharp hope that the set of articles that they have brought
together for this special section, in combination with the thoughtful
commentaries previously discussed, will further stimulate constructive dialogue
around the potential of mentalizing as a translational target. They are grateful
to the editors of this journal for their assistance in laying the foundation for
this continued dialogue.
PMID- 26436586
TI - Maternal effect and speciation: maternal effect contributes to the evolution of
hybrid inviability between Drosophila simulans and Drosophila mauritiana.
AB - Haldane's rule has been the basis of speciation research during the last 30
years. Most studies have focused on the nature of incompatibilities in the hybrid
male, but not much attention has been given to the genetic basis of fertility and
inviability in hybrid females. Hybridizations between Drosophila simulans and
Drosophila mauritiana produce fertile females and sterile males. Here, we re
examined the level of fertility in reciprocal F1 females of these two species and
looked for the presence of maternal effects. Our results show that the reciprocal
F1 females of D. simulans and D. mauritiana hybridizations are fully fertile and
in fact show a significant level of heterosis in the rate of oviposition but
display reduced egg hatching in one direction. Reduced egg hatching was observed
in the progenies of F1 hybrid females with D. mauritiana as mother, the same
cross that showed a stronger negative effect on F1 male fertility. A review of
the literature on the hybridizations in Lepidoptera also showed a maternal effect
on inviability when reciprocal crosses produced asymmetric results. Our findings
point to the importance of maternal effects in the evolution of embryo
inviability and thus enhancing the process of speciation through the evolution of
hybrid inviability.
PMID- 26436587
TI - On the relative contributions of multisensory integration and crossmodal
exogenous spatial attention to multisensory response enhancement.
AB - Two processes that can give rise to multisensory response enhancement (MRE) are
multisensory integration (MSI) and crossmodal exogenous spatial attention. It is,
however, currently unclear what the relative contribution of each of these is to
MRE. We investigated this issue using two tasks that are generally assumed to
measure MSI (a redundant target effect task) and crossmodal exogenous spatial
attention (a spatial cueing task). One block of trials consisted of unimodal
auditory and visual targets designed to provide a unimodal baseline. In two other
blocks of trials, the participants were presented with spatially and temporally
aligned and misaligned audiovisual (AV) targets (0, 50, 100, and 200ms SOA). In
the integration block, the participants were instructed to respond to the onset
of the first target stimulus that they detected (A or V). The instruction for the
cueing block was to respond only to the onset of the visual targets. The targets
could appear at one of three locations: left, center, and right. The participants
were instructed to respond only to lateral targets. The results indicated that
MRE was caused by MSI at 0ms SOA. At 50ms SOA, both crossmodal exogenous spatial
attention and MSI contributed to the observed MRE, whereas the MRE observed at
the 100 and 200ms SOAs was attributable to crossmodal exogenous spatial
attention, alerting, and temporal preparation. These results therefore suggest
that there may be a temporal window in which both MSI and exogenous crossmodal
spatial attention can contribute to multisensory response enhancement.
PMID- 26436588
TI - Breastfeeding: An Unknown Factor to Reduce Heart Disease Risk Among Breastfeeding
Women.
AB - BACKGROUND: Breastfeeding confers many health benefits not only to babies but
also to their lactating mothers. Breastfeeding is a notable protective factor in
the Gail model for breast cancer and is protective for heart disease. Although
individuals in the Appalachian region have lower risk of developing breast
cancer, their risk of heart disease is elevated compared with the national value
for the United States. SUBJECTS AND METHODS: We surveyed 155 predominantly
breastfeeding mothers of toddlers under 3 years old, recruited through parenting
groups, daycares, and county extension in Appalachian West Virginia. Participants
were asked their perceived comparative risks for breast cancer and heart disease
and why they felt their risk was higher, same, or lower than that of the general
population. RESULTS: For breast cancer, 29.7% felt their risk was lower than the
general population. For heart disease, 26.5% felt their risk was lower than the
general population. Although these risks were highly correlated (p=0.006), there
was considerable variability in responses (p<0.03). Qualitative responses for
breast cancer risk frequently included breastfeeding (30.3%) and family history
(30.3%). Qualitative responses for heart disease noted family history (36.1%) but
did not include breastfeeding. A regression analysis found that greater family
history, shorter duration of breastfeeding, and fewer pregnancies were associated
with greater breast cancer risk perceptions. Family history, lower household
income, and current smoking were associated with greater heart disease risk
perceptions. CONCLUSIONS: These well-educated, predominantly lactating women did
not know the protective effects of breastfeeding for heart disease. Increased
educational efforts about heart disease may be helpful to encourage more women to
breastfeed.
PMID- 26436589
TI - PRMT6 increases cytoplasmic localization of p21CDKN1A in cancer cells through
arginine methylation and makes more resistant to cytotoxic agents.
AB - p21(CDKN1A) is known as a potent inhibitor of cyclin-dependent kinase (CDK),
which regulates cell cycle in response to various stimuli, including DNA damage,
on the p53-dependent manner. Here we demonstrate that protein arginine
methyltransferase 6 (PRMT6) methylates p21 at arginine 156 and promotes
phosphorylation of threonine 145 on p21, resulting in the increase of cytoplasmic
localization of p21. The cytoplasmic presence of p21 makes cancer cells more
resistant to cytotoxic agents. Our results indicate that PRMT6 appears to be one
of the key proteins to dysregulate p21 functions in human cancer, and targeting
this pathway may be an appropriate strategy for development of anticancer drugs.
PMID- 26436591
TI - Lysosomal mTORC2/PHLPP1/Akt axis: a new point of control of chaperone-mediated
autophagy.
PMID- 26436590
TI - The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute
myeloid leukemia, impacts prognosis in patients in the intermediate-risk
cytogenetic category, and is associated with a distinctive microRNA signature.
AB - Long non-coding RNAs (lncRNAs) are deregulated in several tumors, although their
role in acute myeloid leukemia (AML) is mostly unknown.We have examined the
expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241
AML patients. We have correlated HOTAIRM1 expression with a miRNA expression
profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215
intermediate-risk AML (IR-AML) patients.The lowest expression level was observed
in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P =
0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently
associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia
free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse
(OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic
value within the favorable molecular subgroup (OR: 3.43; P = 0.009).
Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and
within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover,
HOTAIRM1 expression was associated with a specific 33-microRNA signature that
included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and
has previously been reported to have an independent prognostic value in AML. miR
196b and HOTAIRM1 in combination as a prognostic factor can classify patients as
high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P =
0.004).Determination of HOTAIRM1 level at diagnosis provided relevant prognostic
information in IR-AML and allowed refinement of risk stratification based on
common molecular markers. The prognostic information provided by HOTAIRM1 was
strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1
correlated with a 33-miRNA signature.
PMID- 26436593
TI - Transcriptome asymmetry in synthetic and natural allotetraploid wheats, revealed
by RNA-sequencing.
AB - Allopolyploidization has occurred frequently within the Triticum-Aegilops complex
which provides a suitable system to investigate how allopolyploidization shapes
the expression patterns of duplicated homeologs. We have conducted transcriptome
profiling of leaves and young inflorescences in wild and domesticated tetraploid
wheats, Triticum turgidum ssp. dicoccoides (BBAA) and ssp. durum (BBAA), an
extracted tetraploid (BBAA), and a synthetic tetraploid (S(l) S(l) AA) wheat
together with its diploid parents, Aegilops longissima (S(l) S(l) ) and Triticum
urartu (AA). The two diploid species showed tissue-specific differences in genome
wide ortholog expression, which plays an important role in transcriptome shock
mediated homeolog expression rewiring and hence transcriptome asymmetry in the
synthetic tetraploid. Further changes of homeolog expression apparently occurred
in natural tetraploid wheats, which led to novel transcriptome asymmetry between
the two subgenomes. In particular, our results showed that extremely biased
homeolog expression can occur rapidly upon the allotetraploidzation and this
trend is further enhanced in the course of domestication and evolution of
polyploid wheats. Our results suggest that allopolyploidization is accompanied by
distinct phases of homeolog expression changes, with parental legacy playing
major roles in the immediate rewiring of homeolog expression upon
allopolyploidization, while evolution and domestication under allotetraploidy
drive further homeolog-expression changes toward re-established subgenome
expression asymmetry.
PMID- 26436594
TI - I Can Stomach That! Fearlessness About Death Predicts Attenuated Facial
Electromyography Activity in Response to Death-Related Images.
AB - Objective measures of suicide risk can convey life-saving information to
clinicians, but few such measures exist. This study examined an objective measure
of fearlessness about death (FAD), testing whether FAD relates to self-reported
and physiological aversion to death. Females (n = 87) reported FAD and disgust
sensitivity, and facial electromyography was used to measure physiological facial
responses consistent with disgust while viewing death-related images. FAD
predicted attenuated expression of physiological death aversion, even when
controlling for self-reported death-related disgust sensitivity. Diminished
physiological aversion to death-related stimuli holds promise as an objective
measure of FAD and suicide risk.
PMID- 26436595
TI - Surface and Bulk Effects in Photochemical Reactions and Photomechanical Effects
in Dynamic Molecular Crystals.
AB - The increasing number of reports on photomechanical effects in molecular crystals
necessitates systematic studies to understand the intrinsic and external
effectors that determine and have predictive power of their type and magnitude.
Differential light absorption and product gradient between the surface and the
bulk of the crystal are often invoked to qualitatively explain the mechanical
response of crystals to light; however, the details on how this difference in
photochemical response accounts for macroscopic effects such as surface
modification, deformation, or disintegration of crystals are yet to be
established. Using both bulk- and surface-sensitive analytical techniques, a rare
instance of benzylidenefuranone crystals is studied here, and it is capable of
several distinct types of photomechanical response including surface striation
and delamination, photosalient effect (ballistic disintegration and motion), and
photoinduced bending by dimerization. The results provide a holistic view on
these effects and set the stage for the development of overarching theoretical
models to describe the photomechanics in the ordered solid state.
PMID- 26436596
TI - Role of diode lasers (800-980 nm) as adjuncts to scaling and root planing in the
treatment of chronic periodontitis: a systematic review.
AB - OBJECTIVE: The purpose of this study was to systematically review currently
available evidence regarding the role of diode lasers (810-980 nm) as adjuncts to
scaling and root planing (SRP) in the treatment of chronic periodontitis (CP).
BACKGROUND DATA: Mechanical instrumentation of periodontal tissues followed by
diode laser application leads to complete removal of pocket epithelium compared
with conventional SRP. MATERIALS AND METHODS: To address the focused question "Is
SRP with adjunct diode lasers (810-980 nm) therapy more effective in the
treatment of CP than when CP is treated by SRP alone?" databases were searched
using the following key words: chronic periodontitis, diode laser, surgical, AND
scaling and root planing, periodontal diseases, periodontal therapy, AND
periodontal treatment. Original studies were included. Letters to the editor,
case reports, commentaries, and reviews were excluded. RESULTS: Ten clinical
studies were included. In all studies, patients were systemically healthy, and
cigarette smokers were included in two studies. In five studies, SRP plus diode
laser application was more effective in the treatment of CP than SRP, and three
studies showed no difference. In two studies, there was a moderate reduction in
periodontal inflammation using SRP plus diode laser. The diameter of optic fiber,
laser wavelengths, power, pulse repetition rate, and duration of laser exposure
ranged between 300 MUm and 2 mm, 810-980 nm, 0.8-2.5 W, 10-60 Hz, and 10-100 ms,
respectively. CONCLUSIONS: In CP patients with probing depths <=5 mm, diode
lasers, SRP plus diode laser (800-980 nm) is more effective in the treatment of
CP than when SRP is used alone.
PMID- 26436597
TI - Parasympathomimetic drugs for the treatment of salivary gland dysfunction due to
radiotherapy.
AB - BACKGROUND: This is an updated version of the original Cochrane review on
parasympathomimetic drugs for the treatment of salivary gland dysfunction due to
radiotherapy (published in Issue 3, 2007). Salivary gland dysfunction is a
predictable side effect of radiotherapy to the head and neck region. Pilocarpine
hydrochloride (a choline ester) is licensed in many countries for the treatment
of radiation-induced salivary gland dysfunction. Other parasympathomimetics have
also been used 'off licence' in the treatment of this condition. OBJECTIVES: To
determine the efficacy and tolerability of parasympathomimetic drugs in the
treatment of radiation-induced salivary gland dysfunction (specifically radiation
induced xerostomia). SEARCH METHODS: For this update, we ran searches of the
Cochrane Oral Health Group Trials Register, Cochrane Central Register of
Controlled Trials (CENTRAL 2015, Issue 6), MEDLINE, EMBASE, and CINAHL in July
2015. We checked the reference lists of retrieved articles for additional
studies, contacted experts in the field for unpublished and ongoing trials, and
contacted relevant pharmaceutical companies for unpublished and ongoing trials.
SELECTION CRITERIA: The selection criteria for the review were: 1) randomised
controlled trials; 2) people suffering from radiation-induced salivary gland
dysfunction; 3) people treated with parasympathomimetic drugs; and 4) assessable
data available on primary outcome measure. DATA COLLECTION AND ANALYSIS: The two
review authors independently collected data from the full-text version of
relevant papers including: 1) citation details; 2) participants; 3)
interventions; 4) assessments; 5) outcomes (that is efficacy, tolerability); and
6) quality issues.Due to a lack of appropriate data, we were unable to perform a
meta-analysis. MAIN RESULTS: In the original review, three studies, including a
total of 298 participants, fulfilled the inclusion criteria. All three studies
involved the use of pilocarpine hydrochloride. We have included no additional
studies in the update of the review; we have excluded eight additional
studies.The data suggest that pilocarpine hydrochloride is more effective than
placebo and at least as effective as artificial saliva. The response rate was 42%
to 51%. The time to response was up to 12 weeks. The overall side effect rate was
high, and side effects were the main reason for withdrawal (6% to 15% of
participants taking 5 mg three times a day had to withdraw). The side effects
were usually the result of generalised parasympathomimetic stimulation (for
example sweating, headaches, urinary frequency, vasodilatation). Response rates
were not dose dependent, but side effect rates were dose dependent. AUTHORS'
CONCLUSIONS: There is limited evidence to support the use of pilocarpine
hydrochloride in the treatment of radiation-induced xerostomia. Currently, there
is little evidence to support the use of other parasympathomimetic drugs in the
treatment of radiation-induced xerostomia. Available studies suggest that
approximately half of patients will respond, but side effects can be problematic.
The conclusions of the update are the same as the conclusions of the original
review, since no new relevant studies have been published in the interim.
PMID- 26436598
TI - High-dose chemotherapy and autologous haematopoietic stem cell rescue for
children with high-risk neuroblastoma.
AB - BACKGROUND: Despite the development of new treatment options, the prognosis of
high-risk neuroblastoma patients is still poor; more than half of patients
experience disease recurrence. High-dose chemotherapy and haematopoietic stem
cell rescue (i.e. myeloablative therapy) might improve survival. This review is
the second update of a previously published Cochrane review. OBJECTIVES: Primary
objectiveTo compare the efficacy, that is event-free and overall survival, of
high-dose chemotherapy and autologous bone marrow or stem cell rescue with
conventional therapy in children with high-risk neuroblastoma. Secondary
objectivesTo determine adverse effects (e.g. veno-occlusive disease of the liver)
and late effects (e.g. endocrine disorders or secondary malignancies) related to
the procedure and possible effects of these procedures on quality of life. SEARCH
METHODS: We searched the electronic databases The Cochrane Central Register of
Controlled Trials (CENTRAL) (The Cochrane Library 2014, issue 11), MEDLINE/PubMed
(1966 to December 2014) and EMBASE/Ovid (1980 to December 2014). In addition, we
searched reference lists of relevant articles and the conference proceedings of
the International Society for Paediatric Oncology (SIOP) (from 2002 to 2014),
American Society for Pediatric Hematology and Oncology (ASPHO) (from 2002 to
2014), Advances in Neuroblastoma Research (ANR) (from 2002 to 2014) and American
Society for Clinical Oncology (ASCO) (from 2008 to 2014). We searched for ongoing
trials by scanning the ISRCTN register (www.isrct.com) and the National Institute
of Health Register (www.clinicaltrials.gov). Both registers were screened in
April 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the
efficacy of myeloablative therapy with conventional therapy in high-risk
neuroblastoma patients. DATA COLLECTION AND ANALYSIS: Two authors independently
performed study selection, data extraction and risk of bias assessment. If
appropriate, we pooled studies. The risk ratio (RR) and 95% confidence interval
(CI) was calculated for dichotomous outcomes. For the assessment of survival
data, we calculated the hazard ratio (HR) and 95% CI. We used Parmar's method if
hazard ratios were not reported in the study. We used a random-effects model.
MAIN RESULTS: We identified three RCTs including 739 children. They all used an
age of one year as the cut-off point for pre-treatment risk stratification. The
first updated search identified a manuscript reporting additional follow-up data
for one of these RCTs, while the second update identified an erratum of this
study. There was a significant statistical difference in event-free survival in
favour of myeloablative therapy over conventional chemotherapy or no further
treatment (three studies, 739 patients; HR 0.78, 95% CI 0.67 to 0.90). There was
a significant statistical difference in overall survival in favour of
myeloablative therapy over conventional chemotherapy or no further treatment (two
studies, 360 patients; HR 0.74, 95% CI 0.57 to 0.98). However, when additional
follow-up data were included in the analyses the difference in event-free
survival remained statistically significant (three studies, 739 patients; HR
0.79, 95% CI 0.70 to 0.90), but the difference in overall survival was no longer
statistically significant (two studies, 360 patients; HR 0.86, 95% CI 0.73 to
1.01). The meta-analysis of secondary malignant disease and treatment-related
death did not show any significant statistical differences between the treatment
groups. Data from one study (379 patients) showed a significantly higher
incidence of renal effects, interstitial pneumonitis and veno-occlusive disease
in the myeloablative group compared to conventional chemotherapy, whereas for
serious infections and sepsis no significant difference between the treatment
groups was identified. No information on quality of life was reported. In the
individual studies we evaluated different subgroups, but the results were not
univocal in all studies. All studies had some methodological limitations.
AUTHORS' CONCLUSIONS: Based on the currently available evidence, myeloablative
therapy seems to work in terms of event-free survival. For overall survival there
is currently no evidence of effect when additional follow-up data are included.
No definitive conclusions can be made regarding adverse effects and quality of
life, although possible higher levels of adverse effects should be kept in mind.
A definitive conclusion regarding the effect of myeloablative therapy in
different subgroups is not possible. This systematic review only allows a
conclusion on the concept of myeloablative therapy; no conclusions can be made
regarding the best treatment strategy. Future trials on the use of myeloablative
therapy for high-risk neuroblastoma should focus on identifying the most optimal
induction and/or myeloablative regimen. The best study design to answer these
questions is a RCT. These RCTs should be performed in homogeneous study
populations (e.g. stage of disease and patient age) and have a long-term follow
up. Different risk groups, using the most recent definitions, should be taken
into account.It should be kept in mind that recently the age cut-off for high
risk disease was changed from one year to 18 months. As a result it is possible
that patients with what is now classified as intermediate-risk disease have been
included in the high-risk groups. Consequently the relevance of the results of
these studies to the current practice can be questioned. Survival rates may be
overestimated due to the inclusion of patients with intermediate-risk disease.
PMID- 26436599
TI - Noninvasive positive pressure ventilation for acute respiratory failure following
upper abdominal surgery.
AB - BACKGROUND: Each year, more than four million abdominal surgeries are performed
in the US and over 250,000 in England. Acute respiratory failure, a common
complication that can affect 30% to 50% of people after upper abdominal surgery,
can lead to significant morbidity and mortality. Noninvasive ventilation has been
associated with lower rates of tracheal intubation in adults with acute
respiratory failure, thus reducing the incidence of complications and mortality.
This review compared the effectiveness and safety of noninvasive positive
pressure ventilation (NPPV) versus standard oxygen therapy in the treatment of
acute respiratory failure after upper abdominal surgery. OBJECTIVES: To assess
the effectiveness and safety of noninvasive positive pressure ventilation (NPPV),
that is, continuous positive airway pressure (CPAP) or bilevel NPPV, in reducing
mortality and the rate of tracheal intubation in adults with acute respiratory
failure after upper abdominal surgery, compared to standard therapy (oxygen
therapy), and to assess changes in arterial blood gas levels, hospital and
intensive care unit (ICU) length of stay, gastric insufflation, and anastomotic
leakage. SEARCH METHODS: The date of the last search was 12 May 2015. We searched
the following databases: the Cochrane Handbook for Systematic Reviews of
Interventions (CENTRAL) (2015, Issue 5), MEDLINE (Ovid SP, 1966 to May 2015),
EMBASE (Ovid SP, 1974 to May 2015); the physiotherapy evidence database (PEDro)
(1999 to May 2015); the Cumulative Index to Nursing and Allied Health Literature
(CINAHL, EBSCOhost, 1982 to May 2015), and LILACS (BIREME, 1986 to May 2015). We
reviewed reference lists of included studies and contacted experts. We also
searched grey literature sources. We checked databases of ongoing trials such as
www.controlled-trials.com/ and www.trialscentral.org/. We did not apply language
restrictions. SELECTION CRITERIA: We selected randomized or quasi-randomized
controlled trials involving adults with acute respiratory failure after upper
abdominal surgery who were treated with CPAP or bilevel NPPV with, or without,
drug therapy as standard medical care, compared to adults treated with oxygen
therapy with, or without, standard medical care. DATA COLLECTION AND ANALYSIS:
Two authors independently selected and abstracted data from eligible studies
using a standardized form. We evaluated study quality by assessing allocation
concealment; random sequence generation; incomplete outcome data; blinding of
participants, personnel, and outcome assessors; selective reporting; and
adherence to the intention-to-treat (ITT) principle. MAIN RESULTS: We included
two trials involving 269 participants. The participants were mostly men (67%);
the mean age was 65 years. The trials were conducted in China and Italy (one was
a multicentre trial). Both trials included adults with acute respiratory failure
after upper abdominal surgery. We judged both trials at high risk of bias.
Compared to oxygen therapy, CPAP or bilevel NPPV may reduce the rate of tracheal
intubation (risk ratio (RR) 0.25; 95% confidence interval (CI) 0.08 to 0.83; low
quality evidence) with a number needed to treat for an additional beneficial
outcome of 11. There was very low quality evidence that the intervention may also
reduce ICU length of stay (mean difference (MD) -1.84 days; 95% CI -3.53 to
0.15). We found no differences for mortality (low quality evidence) and hospital
length of stay. There was insufficient evidence to be certain that CPAP or NPPV
had an effect on anastomotic leakage, pneumonia-related complications, and sepsis
or infections. Findings from one trial of 60 participants suggested that bilevel
NPPV, compared to oxygen therapy, may improve blood gas levels and blood pH one
hour after the intervention (partial pressure of arterial oxygen (PaO2): MD 22.5
mm Hg; 95% CI 17.19 to 27.81; pH: MD 0.06; 95% CI 0.01 to 0.11; partial pressure
of arterial carbon dioxide (PCO2) levels (MD -9.8 mm Hg; 95% CI -14.07 to -5.53).
The trials included in this systematic review did not present data on the
following outcomes that we intended to assess: gastric insufflation, fistulae,
pneumothorax, bleeding, skin breakdown, eye irritation, sinus congestion,
oronasal drying, and patient-ventilator asynchrony. AUTHORS' CONCLUSIONS: The
findings of this review indicate that CPAP or bilevel NPPV is an effective and
safe intervention for the treatment of adults with acute respiratory failure
after upper abdominal surgery. However, based on the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) methodology, the quality of the
evidence was low or very low. More good quality studies are needed to confirm
these findings.
PMID- 26436600
TI - Preoperative inspiratory muscle training for postoperative pulmonary
complications in adults undergoing cardiac and major abdominal surgery.
AB - BACKGROUND: Postoperative pulmonary complications (PPCs) have an impact on the
recovery of adults after surgery. It is therefore important to establish whether
preoperative respiratory rehabilitation can decrease the risk of PPCs and to
identify adults who might benefit from respiratory rehabilitation. OBJECTIVES:
Our primary objective was to assess the effectiveness of preoperative inspiratory
muscle training (IMT) on PPCs in adults undergoing cardiac or major abdominal
surgery. We looked at all-cause mortality and adverse events. SEARCH METHODS: We
searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue
10), MEDLINE (1966 to October 2014), EMBASE (1980 to October 2014), CINAHL (1982
to October 2014), LILACS (1982 to October 2014), and ISI Web of Science (1985 to
October 2014). We did not impose any language restrictions. SELECTION CRITERIA:
We included randomized controlled trials that compared preoperative IMT and usual
preoperative care for adults undergoing cardiac or major abdominal surgery. DATA
COLLECTION AND ANALYSIS: Two or more review authors independently identified
studies, assessed trial quality, and extracted data. We extracted the following
information: study characteristics, participant characteristics, intervention
details, and outcome measures. We contacted study authors for additional
information in order to identify any unpublished data. MAIN RESULTS: We included
12 trials with 695 participants; five trials included participants awaiting
elective cardiac surgery and seven trials included participants awaiting elective
major abdominal surgery. All trials contained at least one domain judged to be at
high or unclear risk of bias. Of greatest concern was the risk of bias associated
with inadequate blinding, as it was impossible to blind participants due to the
nature of the study designs. We could pool postoperative atelectasis in seven
trials (443 participants) and postoperative pneumonia in 11 trials (675
participants) in a meta-analysis. Preoperative IMT was associated with a
reduction of postoperative atelectasis and pneumonia, compared with usual care or
non-exercise intervention (respectively; risk ratio (RR) 0.53, 95% confidence
interval (CI) 0.34 to 0.82 and RR 0.45, 95% CI 0.26 to 0.77). We could pool all
cause mortality within postoperative period in seven trials (431 participants) in
a meta-analysis. However, the effect of IMT on all-cause postoperative mortality
is uncertain (RR 0.40, 95% CI 0.04 to 4.23). Eight trials reported the incidence
of adverse events caused by IMT. All of these trials reported that there were no
adverse events in both groups. We could pool the mean duration of hospital stay
in six trials (424 participants) in a meta-analysis. Preoperative IMT was
associated with reduced length of hospital stay (MD -1.33, 95% CI -2.53 to
0.13). According to the Grades of Recommendation, Assessment, Development and
Evaluation (GRADE) Working Group guidelines for evaluating the impact of
healthcare interventions, the overall quality of studies for the incidence of
pneumonia was moderate, whereas the overall quality of studies for the incidence
of atelectasis, all-cause postoperative death, adverse events, and duration of
hospital stay was low or very low. AUTHORS' CONCLUSIONS: We found evidence that
preoperative IMT was associated with a reduction of postoperative atelectasis,
pneumonia, and duration of hospital stay in adults undergoing cardiac and major
abdominal surgery. The potential for overestimation of treatment effect due to
lack of adequate blinding, small-study effects, and publication bias needs to be
considered when interpreting the present findings.
PMID- 26436601
TI - Oral nonsteroidal anti-inflammatory drugs for neuropathic pain.
AB - BACKGROUND: Although often considered to be lacking adequate evidence,
nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the management
of neuropathic pain. Previous surveys found 18% to 47% of affected people
reported using NSAIDs specifically for their neuropathic pain, although possibly
not in the United Kingdom (UK). OBJECTIVES: To assess the analgesic efficacy of
oral NSAIDs for chronic neuropathic pain in adults, when compared to placebo or
another active intervention, and the adverse events associated with its use in
clinical trials. SEARCH METHODS: We searched CENTRAL, MEDLINE, and EMBASE from
inception to 29 May 2015, together with reference lists of retrieved papers and
reviews, and an online trials registry. SELECTION CRITERIA: We included
randomised, double-blind studies of two weeks duration or longer, comparing any
oral NSAID with placebo or another active treatment in chronic neuropathic pain.
DATA COLLECTION AND ANALYSIS: Two review authors independently searched for
studies, extracted efficacy and adverse event data, and examined issues of study
quality. We did not carry out any pooled analysis. MAIN RESULTS: We included two
studies involving 251 participants with chronic low back pain with a neuropathic
component or postherpetic neuralgia; 209 of these participants were involved in a
study of an experimental NSAID not used in clinical practice, and of the
remaining 42, only 16 had neuropathic pain. This represented only third tier
evidence, and was of very low quality. There was no indication of any significant
pain reduction with NSAIDs. Adverse event rates were low, with insufficient
events for any analysis. AUTHORS' CONCLUSIONS: There is no evidence to support or
refute the use of oral NSAIDs to treat neuropathic pain conditions.
PMID- 26436602
TI - Comparison of a restrictive versus liberal red cell transfusion policy for
patients with myelodysplasia, aplastic anaemia, and other congenital bone marrow
failure disorders.
AB - BACKGROUND: Bone marrow failure disorders include a heterogenous group of
disorders, of which myelodysplastic syndrome (MDS), forms the largest subgroup.
MDS is predominantly a disease of the elderly, with many elderly people managed
conservatively with regular allogeneic red blood cell (RBC) transfusions to treat
their anaemia. However, RBC transfusions are not without risk. Despite regular
transfusions playing a central role in treating such patients, the optimal RBC
transfusion strategy (restrictive versus liberal) is currently unclear.
OBJECTIVES: To assess the efficacy and safety of a restrictive versus liberal red
blood cell transfusion strategy for patients with myelodysplasia, acquired
aplastic anaemia, and other inherited bone marrow failure disorders. SEARCH
METHODS: We searched for randomised controlled trials (RCTs) in the Cochrane
Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue
4), Ovid MEDLINE (from 1946), Ovid EMBASE (from 1974), EBSCO CINAHL (from 1937),
the Transfusion Evidence Library (from 1980) and ongoing trial databases to 26th
May 2015. SELECTION CRITERIA: RCTs including patients with long-term bone marrow
failure disorders that require allogeneic blood transfusion, who are not being
actively treated with a haematopoietic stem cell transplant, or intensive
chemotherapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane review
methodology. One author initially screened all references, and excluded any that
were clearly irrelevant or duplicates. Two authors then independently screened
all abstracts of articles, identified by the review search strategy, for
relevancy. Two authors independently assessed the full text of all potentially
relevant articles for eligibility, completed the data extraction and assessed the
studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool.
MAIN RESULTS: We included one trial (13 participants) and identified three
ongoing trials that assess RBC transfusion strategies in people with MDS.The
quality of the evidence was very low across different outcomes according to GRADE
methodology.The one included study randomised participants to a restrictive
[haemoglobin (Hb) transfusion trigger < 72 g/L, 8 participants] or liberal [Hb
trigger < 96 g/L, 5 participants] transfusion policy. There was insufficient
evidence to determine a difference in all-cause mortality (1 RCT; 13
participants; RR 0.13, 95% CI 0.01 to 2.32; very low quality evidence). There was
insufficient evidence to determine a difference in the number of red blood cell
transfusions (1 RCT; 13 participants; 1.8 units per patient per month in the
liberal group, compared to 0.8 in the restrictive arm, no standard deviation was
reported; very low quality evidence). There were no anaemia-related complications
reported (cardiac failure) and no reported effect on activity levels (no
statistics provided). The study did not report: mortality due to
bleeding/infection/transfusion reactions or iron overload, quality of life,
frequency and length of hospital admissions, serious infections (requiring
admission to hospital), or serious bleeding (e.g. WHO/CTCAE grade 3 (or
equivalent) or above). AUTHORS' CONCLUSIONS: This review indicates that there is
currently a lack of evidence for the recommendation of a particular transfusion
strategy for bone marrow failure patients undergoing supportive treatment only.
The one RCT included in this review was only published as an abstract and
contained only 13 participants. Further randomised trials with robust methodology
are required to develop the optimal transfusion strategy for such patients,
particularly as the incidence of the main group of bone marrow failure disorders,
MDS, rises with an ageing population.
PMID- 26436603
TI - Predicting non-familial major physical violent crime perpetration in the US Army
from administrative data.
AB - BACKGROUND: Although interventions exist to reduce violent crime, optimal
implementation requires accurate targeting. We report the results of an attempt
to develop an actuarial model using machine learning methods to predict future
violent crimes among US Army soldiers. METHOD: A consolidated administrative
database for all 975 057 soldiers in the US Army in 2004-2009 was created in the
Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). Of
these soldiers, 5771 committed a first founded major physical violent crime
(murder-manslaughter, kidnapping, aggravated arson, aggravated assault, robbery)
over that time period. Temporally prior administrative records measuring socio
demographic, Army career, criminal justice, medical/pharmacy, and contextual
variables were used to build an actuarial model for these crimes separately among
men and women using machine learning methods (cross-validated stepwise
regression, random forests, penalized regressions). The model was then validated
in an independent 2011-2013 sample. RESULTS: Key predictors were indicators of
disadvantaged social/socioeconomic status, early career stage, prior crime, and
mental disorder treatment. Area under the receiver-operating characteristic curve
was 0.80-0.82 in 2004-2009 and 0.77 in the 2011-2013 validation sample. Of all
administratively recorded crimes, 36.2-33.1% (male-female) were committed by the
5% of soldiers having the highest predicted risk in 2004-2009 and an even higher
proportion (50.5%) in the 2011-2013 validation sample. CONCLUSIONS: Although
these results suggest that the models could be used to target soldiers at high
risk of violent crime perpetration for preventive interventions, final
implementation decisions would require further validation and weighing of
predicted effectiveness against intervention costs and competing risks.
PMID- 26436608
TI - Multinuclear Magnetic Resonance Investigation of Crystalline Alkali Molybdates.
AB - A variety of crystalline alkali molybdate phases are characterized by (23)Na,
(133)Cs, and (95)Mo magic-angle-spinning nuclear magnetic resonance (MAS NMR) to
provide spectroscopic handles for studies of devitrification products in
borosilicate nuclear waste glasses. The NMR parameters obtained from line-shape
simulations are plotted as a function of various structural parameters to discern
trends that may prove useful in the determination of unknown phases. These are
applied to Cs3Na(MoO4)2, the most common precipitate found in cesium- and
molybdenum-bearing model nuclear waste glasses, the crystal structure of which
has not yet been determined, to provide structural constraints that may guide the
refinement of powder X-ray diffraction data.
PMID- 26436605
TI - A mixed-method investigation of patient monitoring and enhanced feedback in
routine practice: Barriers and facilitators.
AB - OBJECTIVE: To investigate the barriers and facilitators of an effective
implementation of an outcome monitoring and feedback system in a UK National
Health Service psychological therapy service. METHOD: An outcome monitoring
system was introduced in two services. Enhanced feedback was given to therapists
after session 4. Qualitative and quantitative methods were used, including
questionnaires for therapists and patients. Thematic analysis was carried out on
written and verbal feedback from therapists. Analysis of patient outcomes for 202
episodes of therapy was compared with benchmark data of 136 episodes of therapy
for which feedback was not given to therapists. RESULTS: Themes influencing the
feasibility and acceptability of the feedback system were the extent to which
therapists integrated the measures and feedback into the therapy, availability of
administrative support, information technology, and complexity of the service.
There were low levels of therapist actions resulting from the feedback, including
discussing the feedback in supervision and with patients. CONCLUSIONS: The
findings support the feasibility and acceptability of setting up a routine system
in a complex service, but a number of challenges and barriers have to be overcome
and therapist differences are apparent. More research on implementation and
effectiveness is needed in diverse clinical settings.
PMID- 26436609
TI - Synthesis and Characterization of Chitosan-Based Polyelectrolyte Complexes Doped
with Xanthene Dyes.
AB - Biocompatible chitosan-based polyelectrolyte complexes (PECs) doped with xanthene
dyes (fluorescein, eosin Y, erythrosin B, rhodamine 6G) were synthesized and
characterized by scanning electron microscopy, dynamic light scattering, zeta
potential measurements, and absorption and luminescence (including polarized,
time-resolved, and phosphorescence) spectroscopy. The results are discussed in
terms of the mechanism and rigidity of dye-PEC binding, the heavy-atom effect in
dyes and PEC stability. Eosin Y is found to be the optimal dopant, providing both
a high dye content in PECs and a high quantum yield of fluorescence.
PMID- 26436610
TI - Serum miR-122 may serve as a biomarker for response to direct acting antivirals:
effect of paritaprevir/R with dasabuvir or ombitasvir on miR-122 in HCV-infected
subjects.
AB - Circulating microRNAs (miRNA) have been intensely investigated as biomarkers in
disease and therapy. Several studies have identified miR-122 as an important
regulator of HCV replication. The effect of new therapies that directly target
the HCV replication life cycle on circulating microRNA levels has not been
elucidated. We performed expression profiling of circulating miRNA in serum in
subjects treated with HCV direct-acting antiviral agents (DAAs). Serum miRNA
levels were evaluated from two studies in HCV GT1-infected treatment-naive
subjects and prior nonresponders to pegylated interferon (pegIFN) and ribavirin
(RBV) who received paritaprevir/ritonavir + dasabuvir + RBV for 12 weeks, and in
treatment-naive genotype (GT)1-3-infected subjects who received
paritaprevir/ritonavir + ombitasvir +/- RBV for 12 weeks. Over 100 different
miRNA species were detected in serum. Of these, levels of miR-122 showed the most
consistent change in response to treatment across all HCV genotypes. In all
subjects, miR-122 showed an average four-fold reduction between baseline and week
2, and remained below baseline through post-treatment week 12 in subjects who
achieved sustained virological response. In contrast, in subjects who did not
achieve SVR, miR-122 levels began to return to baseline levels after the second
week of treatment. The change in miR-122 levels was similar across genotypes, and
was comparable with or without RBV. This is the first report comparing expression
levels of circulating miRNA in HCV GT1-3 subjects treated with IFN-free
combinations of DAAs. The results suggest that serum levels of miR-122 are
reduced following treatment in subjects who achieve SVR, and correlate with HCV
RNA levels across genotypes.
PMID- 26436612
TI - Subnanometer Control of Mean Core Size during Mesofluidic Synthesis of Small
(D(core) < 10 nm) Water-Soluble, Ligand-Stabilized Gold Nanoparticles.
AB - A convenient, single-step synthesis is reported that produces ligand-stabilized,
water-soluble gold nanoparticles (AuNPs) with subnanometer-level precision of the
mean core diameter over a range of 2-9 nm for a series of desired surface
chemistries. The synthesis involves the reduction of a Au(III) species with
sodium borohydride in the presence of a functionalized alkyl thiosulfate (Bunte
salt) to yield thiolate-protected AuNPs. A key advantage of this synthesis is
that simply adjusting the pH of the gold salt solution leads to control over the
AuNP core size. The speciation of Au(III), and therefore the kinetics for its
reduction and the core size produced, depends upon pH. The use of pH as the sole
variable to control core size is a more reliable and convenient method than
traditional approaches that rely on adjusting the concentrations and ratios of
ligand, metal salt, and reducing agent. The average core size increased as the pH
was raised for each ligand studied. Because the influence of pH was different for
each of the ligands, working curves were plotted for each ligand to identify
conditions to synthesize particles with specific, targeted core diameters. Using
this approach, reaction conditions can be rapidly optimized using a combination
of a mesofluidic reactor and small-angle X-ray scattering (SAXS) size analysis.
The use of the mesofluidic reactor was needed to ensure fast mixing given the
rapid kinetics for core formation. Using the reactor, it is possible to obtain
reproducible sizes across multiple syntheses (<1-2% core size variation) and
subnanometer control of the mean core dimensions. The synthetic method
demonstrated here provides an attractive alternative to two-step syntheses
involving ligand exchange because it is more efficient and eliminates the
possibility of nanoparticle core size changes during exchange steps. This
approach enables the development of "size ladders" of particles with the same
surface chemistry for investigations of structure-function relationships.
PMID- 26436611
TI - Association Between Hospitalization With Community-Acquired Laboratory-Confirmed
Influenza Pneumonia and Prior Receipt of Influenza Vaccination.
AB - IMPORTANCE: Few studies have evaluated the relationship between influenza
vaccination and pneumonia, a serious complication of influenza infection.
OBJECTIVE: To assess the association between influenza vaccination status and
hospitalization for community-acquired laboratory-confirmed influenza pneumonia.
DESIGN, SETTING, AND PARTICIPANTS: The Etiology of Pneumonia in the Community
(EPIC) study was a prospective observational multicenter study of
hospitalizations for community-acquired pneumonia conducted from January 2010
through June 2012 at 4 US sites. In this case-control study, we used EPIC data
from patients 6 months or older with laboratory-confirmed influenza infection and
verified vaccination status during the influenza seasons and excluded patients
with recent hospitalization, from chronic care residential facilities, and with
severe immunosuppression. Logistic regression was used to calculate odds ratios,
comparing the odds of vaccination between influenza-positive (case) and influenza
negative (control) patients with pneumonia, controlling for demographics,
comorbidities, season, study site, and timing of disease onset. Vaccine
effectiveness was estimated as (1 - adjusted odds ratio) * 100%. EXPOSURE:
Influenza vaccination, verified through record review. MAIN OUTCOMES AND
MEASURES: Influenza pneumonia, confirmed by real-time reverse-transcription
polymerase chain reaction performed on nasal/oropharyngeal swabs. RESULTS:
Overall, 2767 patients hospitalized for pneumonia were eligible for the study;
162 (5.9%) had laboratory-confirmed influenza. Twenty-eight of 162 cases (17%)
with influenza-associated pneumonia and 766 of 2605 controls (29%) with influenza
negative pneumonia had been vaccinated. The adjusted odds ratio of prior
influenza vaccination between cases and controls was 0.43 (95% CI, 0.28-0.68;
estimated vaccine effectiveness, 56.7%; 95% CI, 31.9%-72.5%). CONCLUSIONS AND
RELEVANCE: Among children and adults hospitalized with community-acquired
pneumonia, those with laboratory-confirmed influenza-associated pneumonia,
compared with those with pneumonia not associated with influenza, had lower odds
of having received influenza vaccination.
PMID- 26436614
TI - Instruments for the evaluation of motor abilities for children with severe
multiple disabilities: A systematic review of the literature.
AB - Based on a systematic review, psychometric characteristics of currently available
instruments on motor abilities of children with disabilities were evaluated, with
the aim to identify candidates for use in children with severe multiple
(intellectual and motor) disabilities. In addition, motor abilities are essential
for independent functioning, but are severely compromised in these children. The
methodological quality of all studies was evaluated with the Consensus Based
Standards for the Selection of Health Status Measurement Instruments (COSMIN)
Checklist; overall levels of evidence per instrument were based on the Cochrane
Back Review Group strategy. As a result, 18 studies with a total of eight
instruments, developed for children with cerebral palsy (CLA, GMFM-88 and LE85),
spinal muscular atrophy (MHFMS), neuromuscular diseases (MFM), disabilities 0-6
years (VAB, WeeFIM), and one developed specifically for children with severe
multiple disabilities (TDMMT) were found. Strong levels of evidence were found
for construct validity of LE85 and MFM and for responsiveness of WeeFIM, but
reliability studies of these instruments had a limited methodological quality. Up
to now studies of the TDMMT resulted in limited and unknown evidence for
structural validity due to the poor methodological quality of reliability
studies. In a next step, the clinical suitability of the instruments for children
with severe multiple disabilities will be evaluate.
PMID- 26436613
TI - Influence of Hepatitis C Virus Sustained Virological Response on
Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected
Patients.
AB - BACKGROUND: We previously reported an association between tryptophan (Trp)
catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is
associated with more rapid evolution of hepatitis C virus (HCV)-associated liver
disease despite antiretroviral therapy (ART), possibly due to immune
dysregulation. We hypothesized that liver fibrosis in HIV/HCV coinfection would
be associated with immune dysfunction and alterations in Trp metabolism. METHODS:
Trp catabolism and inflammatory soluble markers were assessed in plasma samples
from ART-treated HIV/HCV-coinfected patients (n = 90) compared with ART-treated
HIV-monoinfected patients and noninfected subjects. Furthermore, 17 additional
coinfected patients with sustained virological response (SVR) were assessed
longitudinally 6 months after completion of interferon-alpha/ribavirin treatment.
RESULTS: HIV/HCV patients had higher Trp catabolism compared with HIV
monoinfected and healthy individuals. Elevated kynurenine levels in HIV/HCV
patients with liver fibrosis correlated with the prognostic aspartate
aminotransaminase to platelet ratio (APRI scores) and insulin levels.
Furthermore, HIV/HCV patients had elevated levels of disease progression markers
interleukin-6 and induced protein 10 and shared similar levels of markers of
microbial translocation (intestinal fatty acid-binding protein, soluble CD14 and
lipopolysaccharide-binding protein) compared with HIV-monoinfected and healthy
individuals. Successful HCV treatment improved APRI score and markers of disease
progression and microbial translocation although elevated Trp catabolism remained
unchanged 6 months after SVR. CONCLUSION: ART-treated HIV/HCV-coinfected patients
had elevated immunosuppressive Trp catabolism when compared with monoinfected HIV
treated patients, which did not normalize after SVR. These findings suggest that
a necroinflammatory liver syndrome persists through inflammation by Trp
catabolism after 6 month of SVR.
PMID- 26436615
TI - Solid organ transplant in individuals with monoclonal B-cell lymphocytosis and
chronic lymphocytic leukaemia.
PMID- 26436618
TI - Screening Pelvic Examinations in Adult Women: Grand Rounds Discussion From the
Beth Israel Deaconess Medical Center.
AB - Pelvic examinations have historically been a part of regular preventive care.
However, because women can now be screened for cervical cancer at intervals up to
every 5 years, the question of whether women need to be seen annually for routine
pelvic examinations has arisen. In July 2014, the American College of Physicians
(ACP) issued a guideline presenting the available evidence on screening for
pathologic conditions using pelvic examination in adult, asymptomatic women at
average risk. The American College of Obstetricians and Gynecologists (ACOG)
Committee on Gynecologic Practice had previously issued a committee opinion in
August 2012 on the need for annual examinations and provided guidelines on
important elements of this procedure, including when to examine asymptomatic
women. ACOG reaffirmed its initial position after publication of the ACP
guideline. The guidelines differ-the ACP guideline recommends against and the
ACOG committee opinion recommends in favor of routine annual pelvic examination.
This paper summarizes a discussion between an internist and a gynecologist on how
they would balance these recommendations in general and what they would suggest
for an individual patient.
PMID- 26436619
TI - Guidelines International Network: Principles for Disclosure of Interests and
Management of Conflicts in Guidelines.
AB - Conflicts of interest (COIs) have been defined by the American Thoracic Society
as "a divergence between an individual's private interests and his or her
professional obligations such that an independent observer might reasonably
question whether the individual's professional actions or decisions are motivated
by personal gain, such as direct financial, academic advancement, clinical
revenue streams, or community standing." In the context of guideline development,
the concerns are not simply about identifying and disclosing direct financial or
indirect COIs. Despite this recognition, the management of COIs in guidelines is
often unsatisfactory. In response to requests from its international membership
and informed by existing syntheses of the evidence and policies of international
organizations, the Guidelines International Network Board of Trustees developed
guidance on the disclosure of interests and management of COIs. Current
approaches are relatively similar throughout the guideline development community,
with an increasing recognition of the importance of disclosing and managing
indirect COIs. Although there are differences in detail among the approaches, the
similarities allow for the formulation of 9 core principles for managing COIs. In
formulating these principles, the Guidelines International Network Board of
Trustees recognizes that COIs cannot be totally avoided when panel members are
being chosen for certain guidelines or in certain settings; thus, the important
issue is the management of COIs in a fair, judicious, transparent manner.
PMID- 26436621
TI - Celebrating the ACP Centennial: From the Annals Archive-Malaria Treatment.
PMID- 26436622
TI - The Tyranny of Guidelines.
PMID- 26436624
TI - Screening for Thyroid Dysfunction.
PMID- 26436625
TI - Screening for Thyroid Dysfunction.
PMID- 26436616
TI - Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort
Study.
AB - BACKGROUND: Cancer is increasingly common among persons with HIV. OBJECTIVE: To
examine calendar trends in cumulative cancer incidence and hazard rate by HIV
status. DESIGN: Cohort study. SETTING: North American AIDS Cohort Collaboration
on Research and Design during 1996 to 2009. PARTICIPANTS: 86 620 persons with HIV
and 196 987 uninfected adults. MEASUREMENTS: Cancer type-specific cumulative
incidence by age 75 years and calendar trends in cumulative incidence and hazard
rates, each by HIV status. RESULTS: Cumulative incidences of cancer by age 75
years for persons with and without HIV, respectively, were as follows: Kaposi
sarcoma, 4.4% and 0.01%; non-Hodgkin lymphoma, 4.5% and 0.7%; lung cancer, 3.4%
and 2.8%; anal cancer, 1.5% and 0.05%; colorectal cancer, 1.0% and 1.5%; liver
cancer, 1.1% and 0.4%; Hodgkin lymphoma, 0.9% and 0.09%; melanoma, 0.5% and 0.6%;
and oral cavity/pharyngeal cancer, 0.8% and 0.8%. Among persons with HIV,
calendar trends in cumulative incidence and hazard rate decreased for Kaposi
sarcoma and non-Hodgkin lymphoma. For anal, colorectal, and liver cancer,
increasing cumulative incidence, but not hazard rate trends, were due to the
decreasing mortality rate trend (-9% per year), allowing greater opportunity to
be diagnosed. Despite decreasing hazard rate trends for lung cancer, Hodgkin
lymphoma, and melanoma, cumulative incidence trends were not seen because of the
compensating effect of the declining mortality rate. LIMITATION: Secular trends
in screening, smoking, and viral co-infections were not evaluated. CONCLUSION:
Cumulative cancer incidence by age 75 years, approximating lifetime risk in
persons with HIV, may have clinical utility in this population. The high
cumulative incidences by age 75 years for Kaposi sarcoma, non-Hodgkin lymphoma,
and lung cancer support early and sustained antiretroviral therapy and smoking
cessation.
PMID- 26436626
TI - Pain, Opioids, and Addiction.
PMID- 26436627
TI - Pain, Opioids, and Addiction.
PMID- 26436628
TI - The PRISMA Extension Statement.
PMID- 26436629
TI - The PRISMA Extension Statement.
PMID- 26436630
TI - Medicare's Annual Wellness Visit in a Large Health Care Organization: Who Is
Using It?
PMID- 26436632
TI - Web Exclusives. Annals Graphic Medicine: Sign Out.
PMID- 26436631
TI - In the Clinic: Community-Acquired Pneumonia.
PMID- 26436633
TI - Short-term and long-term effects on visual word recognition.
AB - Effects of lexical and sublexical variables on visual word recognition are often
treated as homogeneous across participants and stable over time. In this study,
we examine the modulation of frequency, length, syllable and bigram frequency,
orthographic neighborhood, and graphophonemic consistency effects by (a)
individual differences, and (b) item repetition. A group of 129 participants
performed lexical decision and naming, in counterbalanced order, using a set of
150 Greek words in which these variables were decorrelated. Frequency, length,
and syllable frequency effects were reduced by a preceding task. Length effects
were inversely related to years of education. Neighborhood effects depended on
the metric used. There were no significant effects or interactions of bigram
frequency or consistency. The results suggest that exposure to a word causes
transient effects that may cumulatively develop into permanent individual
differences. Models of word recognition must incorporate item-specific learning
to account for these findings.
PMID- 26436634
TI - Phonological activation of word meanings in grade 5 readers.
AB - Three experiments examined the role of phonology in the activation of word
meanings in Grade 5 students. In Experiment 1, homophone and spelling control
errors were embedded in a story context and participants performed a proofreading
task as they read for meaning. For both good and poor readers, more homophone
errors went undetected than spelling control errors. In Experiments 2 and 3,
homophone and spelling control errors were in sentence contexts. Experiment 2
used an online sentence verification task, and found that both good and poor
readers were less accurate when sentences contained a homophone error than a
spelling control error. Furthermore, a difference between the 2 types of
sentences was observed even when participants were concurrently performing an
articulation task. In Experiment 3, initial reading times were shorter on
homophone errors than on spelling controls, and participants were less likely to
make a regression from homophone errors than spelling controls. These experiments
provide clear evidence that phonology makes an important contribution to the
activation of word meanings in Grade 5 readers.
PMID- 26436635
TI - Observation of S = 1/2 quasi-1D magnetic and magneto-dielectric behavior in a
cubic SrCuTe2O6.
AB - We investigate the magnetic, thermal, and dielectric properties of SrCuTe2O6,
which is isostructural to PbCuTe2O6, a recently found, Cu-based 3D frustrated
magnet with a corner-sharing triangular spin network having dominant first and
second nearest neighbor (nn) couplings (Koteswararao et al 2014 Phys. Rev. B 90
035141). Although SrCuTe2O6 has a structurally similar spin network, the magnetic
data exhibit the characteristic features of a typical quasi-1D magnet, which
mainly resulted from the magnetically dominant third nn coupling, uniform chains.
The magnetic properties of this system are studied via magnetization (M), heat
capacity (C p ), dielectric constant ([Formula: see text]), and measurements
along with ab initio band structure calculations. The magnetic susceptibility
[Formula: see text] data show a broad maximum at 32 K and the system orders at
low temperatures [Formula: see text] K and [Formula: see text] K, respectively.
The analysis of the [Formula: see text] data gives an intra-chain coupling,
[Formula: see text], to be about ~ - 42 K with non-negligible frustrated inter
chain couplings ([Formula: see text] and [Formula: see text]). The hopping
parameters obtained from the LDA band structure calculations also suggest the
presence of coupled uniform chains. The observation of simultaneous anomalies in
[Formula: see text] at [Formula: see text] and [Formula: see text] suggests the
presence of a magneto-dielectric effect in SrCuTe2O6. A magnetic phase diagram is
also built based on the M, C p , and [Formula: see text] results.
PMID- 26436636
TI - Deoxygenative C-C Bond-Forming Processes via a Net Four-Electron Reductive
Coupling.
AB - The nickel-catalyzed coupling of enones or enals with alkynes in the presence of
silane and titanium alkoxide reductants provides direct access to skipped diene
products. The process involves a net four-electron reductive coupling and
proceeds with deoxygenation of the starting enone or enal. A new class of well
defined nickel(0) precatalysts bearing an unhindered N-heterocyclic carbene
ligand, which was developed in optimization of the process, is essential for the
efficiency of the transformation. The strategy allows the high reactivity of
alpha,beta-unsaturated carbonyl substrates to be utilized in couplings with
simultaneous extrusion of the oxygen atom, thus enabling a traceless strategy for
alkene installation.
PMID- 26436637
TI - Spontaneous Packaging and Hypothermic Storage of Mammalian Cells with a Cell
Membrane-Mimetic Polymer Hydrogel in a Microchip.
AB - Currently, continuous culture/passage and cryopreservation are two major, well
established methods to provide cultivated mammalian cells for experiments in
laboratories. Due to the lack of flexibility, however, both laboratory-oriented
methods are unable to meet the need for rapidly growing cell-based applications,
which require cell supply in a variety of occasions outside of laboratories.
Herein, we report spontaneous packaging and hypothermic storage of mammalian
cells under refrigerated (4 degrees C) and ambient conditions (25 degrees C)
using a cell-membrane-mimetic methacryloyloxyethyl phosphorylcholine (MPC)
polymer hydrogel incorporated within a glass microchip. Its capability for
hypothermic storage of cells was comparatively evaluated over 16 days. The
results reveal that the cytocompatible MPC polymer hydrogel, in combination with
the microchip structure, enabled hypothermic storage of cells with quite high
viability, high intracellular esterase activity, maintained cell membrane
integrity, and small morphological change for more than 1 week at 4 degrees C
and at least 4 days at 25 degrees C. Furthermore, the stored cells could be
released from the hydrogel and exhibited the ability to adhere to a surface and
achieve confluence under standard cell culture conditions. Both hypothermic
storage conditions are ordinary flexible conditions which can be easily
established in places outside of laboratories. Therefore, cell packaging and
storage using the hydrogel incorporated within the microchip would be a promising
miniature and portable solution for flexible supply and delivery of small amounts
of cells from bench to bedside.
PMID- 26436638
TI - Self-assembled hybrid metal oxide base catalysts prepared by simply mixing with
organic modifiers.
AB - Multidentate materials formed by simply mixing heterogeneous and homogeneous
components are promising for construction of versatile active sites on the
surface of heterogeneous compounds, however, to the best of our knowledge, there
are no reports on such materials. Self-assembly of hetero-hybrid catalytic
materials occurs when heterogeneous catalysts having adjacent Lewis acid-Lewis
base sites are mixed with an organic modifier that contains at least two Lewis
base functional groups. Here we demonstrate the strategy by combining cerium
oxide and 2-cyanopyridine that self-assembles to form a charge-transfer complex
in methanol that exhibits a 2,000-fold increase in reaction rate for
hydromethoxylation of acrylonitrile with high selectivity compared with cerium
oxide or 2-cyanopyridine alone. The catalytic system is applied to the
transesterification and Knoevenagel condensation affording 14-fold and 11-fold
higher activity, respectively, than cerium oxide alone. These results demonstrate
the potential versatility of the catalytic system and the generality of the
catalyst preparation strategy.
PMID- 26436639
TI - Transsynaptic Tracing from Peripheral Targets with Pseudorabies Virus Followed by
Cholera Toxin and Biotinylated Dextran Amines Double Labeling.
AB - Transsynaptic tracing has become a powerful tool used to analyze central
efferents that regulate peripheral targets through multi-synaptic circuits. This
approach has been most extensively used in the brain by utilizing the swine
pathogen pseudorabies virus (PRV)(1). PRV does not infect great apes, including
humans, so it is most commonly used in studies on small mammals, especially
rodents. The pseudorabies strain PRV152 expresses the enhanced green fluorescent
protein (eGFP) reporter gene and only crosses functional synapses retrogradely
through the hierarchical sequence of synaptic connections away from the infection
site(2,3). Other PRV strains have distinct microbiological properties and may be
transported in both directions (PRV-Becker and PRV-Kaplan)(4,5). This protocol
will deal exclusively with PRV152. By delivering the virus at a peripheral site,
such as muscle, it is possible to limit the entry of the virus into the brain
through a specific set of neurons. The resulting pattern of eGFP signal
throughout the brain then resolves the neurons that are connected to the
initially infected cells. As the distributed nature of transsynaptic tracing with
pseudorabies virus makes interpreting specific connections within an identified
network difficult, we present a sensitive and reliable method employing
biotinylated dextran amines (BDA) and cholera toxin subunit b (CTb) for
confirming the connections between cells identified using PRV152. Immunochemical
detection of BDA and CTb with peroxidase and DAB (3, 3'-diaminobenzidine) was
chosen because they are effective at revealing cellular processes including
distal dendrites(6-11).
PMID- 26436640
TI - Deterministic processes vary during community assembly for ecologically
dissimilar taxa.
AB - The continuum hypothesis states that both deterministic and stochastic processes
contribute to the assembly of ecological communities. However, the contextual
dependency of these processes remains an open question that imposes strong
limitations on predictions of community responses to environmental change. Here
we measure community and habitat turnover across multiple vertical soil horizons
at 183 sites across Scotland for bacteria and fungi, both dominant and
functionally vital components of all soils but which differ substantially in
their growth habit and dispersal capability. We find that habitat turnover is the
primary driver of bacterial community turnover in general, although its
importance decreases with increasing isolation and disturbance. Fungal
communities, however, exhibit a highly stochastic assembly process, both neutral
and non-neutral in nature, largely independent of disturbance. These findings
suggest that increased focus on dispersal limitation and biotic interactions are
necessary to manage and conserve the key ecosystem services provided by these
assemblages.
PMID- 26436642
TI - Design and analysis of field studies with bees: A critical review of the draft
EFSA guidance.
AB - The specific protection goal, primary assessment endpoints, acceptable effect
thresholds, and experimental design proposed in the European Food Safety
Authority (EFSA) update of the bee guidance document are subjected to critical
review. It is concluded that the negligible effect criteria were established
without sufficient regulatory definition and without convincing scientific
argumentation. For the assessment endpoints, effects on hive strength lack
temporal definition and the reduction to numbers of bees is inappropriate to
evaluate effects. Restricting mortality assessments to homing failure is not
theoretically justified and specific criteria were incorrectly derived. The
combination of acute effect estimates with models for chronic stressors is biased
risk assessment and a temporal basis for the acceptability of effects is missing.
Effects on overwintering success cannot be experimentally assessed using the
proposed criteria. The experimental methodology proposed is inappropriate and the
logistical consequences, in particular those related to replication and land use
are such that field studies are no longer a feasible option for the risk
assessment. It may be necessary to explore new lines of thought for the set-up of
field studies and to clearly separate experimentation from monitoring. Integr
Environ Assess Manag 2016;12:422-428. (c) 2015 SETAC.
PMID- 26436641
TI - Cell Sorting of Neural Stem and Progenitor Cells from the Adult Mouse
Subventricular Zone and Live-imaging of their Cell Cycle Dynamics.
AB - Neural stem cells (NSCs) in the subventricular zone of the lateral ventricles
(SVZ) sustain olfactory neurogenesis throughout life in the mammalian brain. They
successively generate transit amplifying cells (TACs) and neuroblasts that
differentiate into neurons once they integrate the olfactory bulbs. Emerging
fluorescent activated cell sorting (FACS) techniques have allowed the isolation
of NSCs as well as their progeny and have started to shed light on gene
regulatory networks in adult neurogenic niches. We report here a cell sorting
technique that allows to follow and distinguish the cell cycle dynamics of the
above-mentioned cell populations from the adult SVZ with a LeX/EGFR/CD24 triple
staining. Isolated cells are then plated as adherent cells to explore in details
their cell cycle progression by time-lapse video microscopy. To this end, we use
transgenic Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) mice in which
cells are red-fluorescent during G1 phase due to a G1 specific red-Cdt1 reporter.
This method has recently revealed that proliferating NSCs progressively lengthen
their G1 phase during aging, leading to neurogenesis impairment. This method is
easily transposable to other systems and could be of great interest for the study
of the cell cycle dynamics of brain cells in the context of brain pathologies.
PMID- 26436643
TI - Bringing GRACE Down to Earth.
PMID- 26436644
TI - Toward Adenotonsillectomy in Children: A Review for the General Pediatrician.
AB - Adenotonsillectomy is one of the most common surgical procedures performed in
children, with more than half a million procedures performed annually. We provide
a review of the procedure, including indications, contraindications,
perioperative issues, and current controversies. A more in-depth discussion of
indications for sleep-disordered breathing and recurrent throat infections is
performed. We provide a reasonable approach to these conditions for the general
pediatrician. Finally, we discuss selected areas of current controversies: the
role of preoperative polysomnogram, postoperative weight gain, and effects on
immune function.
PMID- 26436645
TI - The relationship between session frequency and psychotherapy outcome in a
naturalistic setting.
AB - OBJECTIVE: The dose-response relationship in psychotherapy has been examined
extensively, but few studies have included session frequency as a component of
psychotherapy "dose." Studies that have examined session frequency have indicated
that it may affect both the speed and the amount of recovery. No studies were
found examining the clinical significance of this construct in a naturalistic
setting, which is the aim of the current study. METHOD: Using an archival
database of session-by-session Outcome Questionnaire 45 (OQ-45) measures over 17
years, change trajectories of 21,488 university counseling center clients (54.9%
female, 85.0% White, mean age = 22.5) were examined using multilevel modeling,
including session frequency at the occasion level. Of these clients, subgroups
that attended therapy approximately weekly or fortnightly were compared to each
other for differences in speed of recovery (using multilevel Cox regression) and
clinically significant change (using multilevel logistic regression). RESULTS:
Results indicated that more frequent therapy was associated with steeper recovery
curves (Cohen's f2 = 0.07; an effect size between small and medium). When
comparing weekly and fortnightly groups, clinically significant gains were
achieved faster for those attending weekly sessions; however, few significant
differences were found between groups in total amount of change in therapy.
CONCLUSIONS: Findings replicated previous session frequency literature and
supported a clinically significant effect, where higher session frequency
resulted in faster recovery. Session frequency appears to be an impactful
component in delivering more efficient psychotherapy, and it is important to
consider in individual treatment planning, institutional policy, and future
research.
PMID- 26436646
TI - Investigating Functional Regeneration in Organotypic Spinal Cord Co-cultures
Grown on Multi-electrode Arrays.
AB - Adult higher vertebrates have a limited potential to recover from spinal cord
injury. Recently, evidence emerged that propriospinal connections are a promising
target for intervention to improve functional regeneration. So far, no in vitro
model exists that grants the possibility to examine functional recovery of
propriospinal fibers. Therefore, a representative model that is based on two
organotypic spinal cord sections of embryonic rat, cultured next to each other on
multi-electrode arrays (MEAs) was developed. These slices grow and, within a few
days in vitro, fuse along the sides facing each other. The design of the used
MEAs permits the performance of lesions with a scalpel blade through this fusion
site without inflicting damage on the MEAs. The slices show spontaneous activity,
usually organized in network activity bursts, and spatial and temporal activity
parameters such as the location of burst origins, speed and direction of their
propagation and latencies between bursts can be characterized. Using these
features, it is also possible to assess functional connection of the slices by
calculating the amount of synchronized bursts between the two sides. Furthermore,
the slices can be morphologically analyzed by performing immunohistochemical
stainings after the recordings. Several advantages of the used techniques are
combined in this model: the slices largely preserve the original tissue
architecture with intact local synaptic circuitry, the tissue is easily and
repeatedly accessible and neuronal activity can be detected simultaneously and
non-invasively in a large number of spots at high temporal resolution. These
features allow the investigation of functional regeneration of intraspinal
connections in isolation in vitro in a sophisticated and efficient way.
PMID- 26436647
TI - MicroRNA-223 is a crucial mediator of PPARgamma-regulated alternative macrophage
activation.
AB - Polarized activation of adipose tissue macrophages (ATMs) is crucial for
maintaining adipose tissue function and mediating obesity-associated
cardiovascular risk and metabolic abnormalities; however, the regulatory network
of this key process is not well defined. Here, we identified a PPARgamma/microRNA
223 (miR-223) regulatory axis that controls macrophage polarization by targeting
distinct downstream genes to shift the cellular response to various stimuli. In
BM-derived macrophages, PPARgamma directly enhanced miR-223 expression upon
exposure to Th2 stimuli. ChIP analysis, followed by enhancer reporter assays,
revealed that this effect was mediated by PPARgamma binding 3 PPARgamma
regulatory elements (PPREs) upstream of the pre-miR-223 coding region. Moreover,
deletion of miR-223 impaired PPARgamma-dependent macrophage alternative
activation in cells cultured ex vivo and in mice fed a high-fat diet. We
identified Rasa1 and Nfat5 as genuine miR-223 targets that are critical for
PPARgamma-dependent macrophage alternative activation, whereas the
proinflammatory regulator Pknox1, which we reported previously, mediated miR-223
regulated macrophage classical activation. In summary, this study provides
evidence to support the crucial role of a PPARgamma/miR-223 regulatory axis in
controlling macrophage polarization via distinct downstream target genes.
PMID- 26436648
TI - Intravital imaging of intestinal lacteals unveils lipid drainage through
contractility.
AB - Lacteals are lymphatic vessels located at the center of each intestinal villus
and provide essential transport routes for lipids and other lipophilic molecules.
However, it is unclear how absorbed molecules are transported through the
lacteal. Here, we used reporter mice that express GFP under the control of the
lymphatic-specific promoter Prox1 and a custom-built confocal microscope and
performed intravital real-time visualization of the absorption and transport
dynamics of fluorescence-tagged fatty acids (FAs) and various exogenous molecules
in the intestinal villi in vivo. These analyses clearly revealed transepithelial
absorption of these molecules via enterocytes, diffusive distribution over the
lamina propria, and subsequent transport through lacteals. Moreover, we observed
active contraction of lacteals, which seemed to be directly involved in dietary
lipid drainage. Our analysis revealed that the smooth muscles that surround each
lacteal are responsible for contractile dynamics and that lacteal contraction is
ultimately controlled by the autonomic nervous system. These results indicate
that the lacteal is a unique organ-specific lymphatic system and does not merely
serve as a passive conduit but as an active pump that transports lipids.
Collectively, using this efficient imaging method, we uncovered drainage of
absorbed molecules in small intestinal villus lacteals and the involvement of
lacteal contractibility.
PMID- 26436649
TI - Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity.
AB - IgG molecules exert both pro- and antiinflammatory effector functions based on
the composition of the fragment crystallizable (Fc) domain glycan. Sialylated IgG
Fc domains have antiinflammatory properties that are attributed to their ability
to increase the activation threshold of innate effector cells to immune complexes
by stimulating the upregulation of the inhibitory Fcgamma receptor IIB
(FcgammaRIIB). Here, we report that IgG Fc sialylation of human monoclonal IgG1
molecules impairs their efficacy to induce complement-mediated cytotoxicity
(CDC). Fc sialylation of a CD20-targeting antibody had no impact on antibody
dependent cellular cytotoxicity and did not change the affinity of the antibody
for activating Fcgamma receptors. In contrast, the presence of sialic acid
abrogated the increased binding of C1q to Fc-galactosylated IgG1 and resulted in
decreased levels of C3b deposition on the cell surface. Similar to monoclonal
antibodies, sialic acid inhibited the increased C1q binding to galactosylated Fc
fragments in human polyclonal IgG. In sera derived from patients with chronic
inflammatory demyelinating polyneuropathy, an autoimmune disease of the
peripheral nervous system in which humoral immune responses mediate tissue
damage, induction of IgG Fc sialylation was associated with clinical disease
remission. Thus, impairment of CDC represents an FcgammaR-independent mechanism
by which Fc-sialylated glycovariants might limit proinflammatory IgG effector
functions.
PMID- 26436650
TI - MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes.
AB - Calcium/calcineurin signaling is critical for normal cellular physiology.
Abnormalities in this pathway cause many diseases, including podocytopathy;
therefore, understanding the mechanisms that underlie the regulation of
calcium/calcineurin signaling is essential. Here, we showed that critical
components of calcium/calcineurin signaling, including TRPC6, PPP3CA, PPP3CB,
PPP3R1, and NFATC3, are the targets of the microRNA-30 family (miR-30s). We found
that these 5 genes are highly expressed as mRNA, but the level of the proteins is
low in normal podocytes. Conversely, protein levels were markedly elevated in
podocytes from rats treated with puromycin aminonucleoside (PAN) and from
patients with focal segmental glomerulosclerosis (FSGS). In both FSGS patients
and PAN-treated rats, miR-30s were downregulated in podocytes. In cultured
podocytes, PAN or a miR-30 sponge increased TRPC6, PPP3CA, PPP3CB, PPP3R1, and
NFATC3 expression; calcium influx; intracellular Ca2+ concentration; and
calcineurin activity. Moreover, NFATC3 nuclear translocation, synaptopodin
degradation, integrin beta3 (ITGB3) activation, and actin fiber loss, which are
downstream of calcium/calcineurin signaling, were induced by miR-30 reduction but
blocked by the calcineurin inhibitor FK506. Podocyte-specific expression of the
miR-30 sponge in mice increased calcium/calcineurin pathway component protein
expression and calcineurin activity. The mice developed podocyte foot process
effacement and proteinuria, which were prevented by FK506. miR-30s also regulated
calcium/calcineurin signaling in cardiomyocytes. Together, our results identify
miR-30s as essential regulators of calcium/calcineurin signaling.
PMID- 26436653
TI - Statistical Models for the Analysis and Design of Digital Polymerase Chain
Reaction (dPCR) Experiments.
AB - Statistical methods for the analysis and design of experiments using digital PCR
(dPCR) have received only limited attention and have been misused in many
instances. To address this issue and to provide a more general approach to the
analysis of dPCR data, we describe a class of statistical models for the analysis
and design of experiments that require quantification of nucleic acids. These
models are mathematically equivalent to generalized linear models of binomial
responses that include a complementary, log-log link function and an offset that
is dependent on the dPCR partition volume. These models are both versatile and
easy to fit using conventional statistical software. Covariates can be used to
specify different sources of variation in nucleic acid concentration, and a
model's parameters can be used to quantify the effects of these covariates. For
purposes of illustration, we analyzed dPCR data from different types of
experiments, including serial dilution, evaluation of copy number variation, and
quantification of gene expression. We also showed how these models can be used to
help design dPCR experiments, as in selection of sample sizes needed to achieve
desired levels of precision in estimates of nucleic acid concentration or to
detect differences in concentration among treatments with prescribed levels of
statistical power.
PMID- 26436652
TI - Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses
and regulates cardiac homeostasis.
AB - Cardiomyopathy is a common human disorder that is characterized by contractile
dysfunction and cardiac remodeling. Genetic mutations and altered expression of
genes encoding many signaling molecules and contractile proteins are associated
with cardiomyopathy; however, how cardiomyocytes sense pathophysiological
stresses in order to then modulate cardiac remodeling remains poorly understood.
Here, we have described a regulator in the heart that harmonizes the progression
of cardiac hypertrophy and dilation. We determined that expression of the myocyte
enriched protein cardiac ISL1-interacting protein (CIP, also known as MLIP) is
reduced in patients with dilated cardiomyopathy. As CIP is highly conserved
between human and mouse, we evaluated the effects of CIP deficiency on cardiac
remodeling in mice. Deletion of the CIP-encoding gene accelerated progress from
hypertrophy to heart failure in several cardiomyopathy models. Conversely,
transgenic and AAV-mediated CIP overexpression prevented pathologic remodeling
and preserved cardiac function. CIP deficiency combined with lamin A/C deletion
resulted in severe dilated cardiomyopathy and cardiac dysfunction in the absence
of stress. Transcriptome analyses of CIP-deficient hearts revealed that the p53-
and FOXO1-mediated gene networks related to homeostasis are disturbed upon
pressure overload stress. Moreover, FOXO1 overexpression suppressed stress
induced cardiomyocyte hypertrophy in CIP-deficient cardiomyocytes. Our studies
identify CIP as a key regulator of cardiomyopathy that has potential as a
therapeutic target to attenuate heart failure progression.
PMID- 26436651
TI - Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune
vasculitis.
AB - Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that
is associated with granulomatous inflammation and the presence of anti-neutrophil
cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously
determined that PR3 on the surface of apoptotic neutrophils interferes with
induction of antiinflammatory mechanisms following phagocytosis of these cells by
macrophages. Here, we demonstrate that enzymatically active membrane-associated
PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including
granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88
signaling pathway and was dependent on the synthesis of NO, as macrophages from
animals lacking these pathways did not exhibit a PR3-associated proinflammatory
response. The PR3-induced microenvironment facilitated recruitment of
inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and
neutrophils, which were observed in close proximity within granulomatous lesions
in the lungs of GPA patients. In different murine models of apoptotic cell
injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell
generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic
cells induced a Th17 response, revealing a GPA-specific mechanism of immune
polarization. Accordingly, circulating CD4+ T cells from GPA patients had a
skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts
immune silencing associated with clearance of apoptotic neutrophils and provide
insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology.
PMID- 26436654
TI - Recruitment, response rates and characteristics of 5511 people enrolled in a
prospective clinical cohort study: head and neck 5000.
PMID- 26436656
TI - Fate of Carbohydrates and Lignin during Composting and Mycelium Growth of
Agaricus bisporus on Wheat Straw Based Compost.
AB - In wheat straw based composting, enabling growth of Agaricus bisporus mushrooms,
it is unknown to which extent the carbohydrate-lignin matrix changes and how much
is metabolized. In this paper we report yields and remaining structures of the
major components. During the Phase II of composting 50% of both xylan and
cellulose were metabolized by microbial activity, while lignin structures were
unaltered. During A. bisporus' mycelium growth (Phase III) carbohydrates were
only slightly consumed and xylan was found to be partially degraded. At the same
time, lignin was metabolized for 45% based on pyrolysis GC/MS. Remaining lignin
was found to be modified by an increase in the ratio of syringyl (S) to guaiacyl
(G) units from 0.5 to 0.7 during mycelium growth, while fewer decorations on the
phenolic skeleton of both S and G units remained.
PMID- 26436655
TI - Genome-Wide Detection and Analysis of Multifunctional Genes.
AB - Many genes can play a role in multiple biological processes or molecular
functions. Identifying multifunctional genes at the genome-wide level and
studying their properties can shed light upon the complexity of molecular events
that underpin cellular functioning, thereby leading to a better understanding of
the functional landscape of the cell. However, to date, genome-wide analysis of
multifunctional genes (and the proteins they encode) has been limited. Here we
introduce a computational approach that uses known functional annotations to
extract genes playing a role in at least two distinct biological processes. We
leverage functional genomics data sets for three organisms--H. sapiens, D.
melanogaster, and S. cerevisiae--and show that, as compared to other annotated
genes, genes involved in multiple biological processes possess distinct
physicochemical properties, are more broadly expressed, tend to be more central
in protein interaction networks, tend to be more evolutionarily conserved, and
are more likely to be essential. We also find that multifunctional genes are
significantly more likely to be involved in human disorders. These same features
also hold when multifunctionality is defined with respect to molecular functions
instead of biological processes. Our analysis uncovers key features about
multifunctional genes, and is a step towards a better genome-wide understanding
of gene multifunctionality.
PMID- 26436657
TI - An Improved Approach of Mesh Segmentation to Extract Feature Regions.
AB - The objective of this paper is to extract concave and convex feature regions via
segmenting surface mesh of a mechanical part whose surface geometry exhibits
drastic variations and concave-convex features are equally important when
modeling. Referring to the original approach based on the minima rule (MR) in
cognitive science, we have created a revised minima rule (RMR) and presented an
improved approach based on RMR in the paper. Using the logarithmic function in
terms of the minimum curvatures that are normalized by the expectation and the
standard deviation on the vertices of the mesh, we determined the solution
formulas for the feature vertices according to RMR. Because only a small range of
the threshold parameters was selected from in the determined formulas, an
iterative process was implemented to realize the automatic selection of
thresholds. Finally according to the obtained feature vertices, the feature edges
and facets were obtained by growing neighbors. The improved approach overcomes
the inherent inadequacies of the original approach for our objective in the
paper, realizes full automation without setting parameters, and obtains better
results compared with the latest conventional approaches. We demonstrated the
feasibility and superiority of our approach by performing certain experimental
comparisons.
PMID- 26436658
TI - Improvement in B1+ Homogeneity and Average Flip Angle Using Dual-Source Parallel
RF Excitation for Cardiac MRI in Swine Hearts.
AB - Cardiac MRI may benefit from increased polarization at high magnetic field
strength of 3 Tesla but is challenged by increased field inhomogeneity. Initial
human studies have shown that the radiofrequency (RF) excitation field (B1+) used
for signal excitation in the heart is both inhomogeneous and significantly lower
than desired, potentially leading to image artifacts and biased quantitative
measures. Recently, multi-channel transmit systems have been introduced allowing
localized patient specific RF shimming based on acquired calibration B1+ maps.
Some prior human studies have shown lower than desired mean flip angles in the
hearts of large patients even after RF shimming. Here, 100 cardiac B1+ map pairs
before and after RF shimming were acquired in 55 swine. The mean flip angle and
the coefficient of variation (CV) of the flip angle in the heart were determined
before and after RF shimming. Mean flip angle, CV, and RF shim values (power
ratio and phase difference between the two transmit channels) were tested for
correlation with cross sectional body area and the Right-Left/Anterior-Posterior
ratio. RF shimming significantly increased the mean flip angle in swine heart
from 74.4+/-6.7% (mean +/- standard deviation) to 94.7+/-4.8% of the desired flip
angle and significantly reduced CV from 0.11+/-0.03 to 0.07+/-0.02 (p<<1e-10 for
both). These results compare well with several previous human studies, except
that the mean flip angle in the human heart only improved to 89% with RF
shimming, possibly because the RF shimming routine does not consider safety
constraints in very large patients. Additionally, mean flip angle decreased and
CV increased with larger cross sectional body area, however, the RF shimming
parameters did not correlate with cross sectional body area. RF shim power ratio
correlated weakly with Right-Left/Anterior-Posterior ratio but phase difference
did not, further substantiating the need for subject specific cardiac RF
shimming.
PMID- 26436660
TI - Fabrication and Doping Methods for Silicon Nano- and Micropillar Arrays for Solar
Cell Applications: A Review.
AB - Silicon is one of the main components of commercial solar cells and is used in
many other solar-light-harvesting devices. The overall efficiency of these
devices can be increased by the use of structured surfaces that contain nanometer
to micrometer-sized pillars with radial p/n junctions. High densities of such
structures greatly enhance the light-absorbing properties of the device, whereas
the 3D p/n junction geometry shortens the diffusion length of minority carriers
and diminishes recombination. Due to the vast silicon nano- and microfabrication
toolbox that exists nowadays, many versatile methods for the preparation of such
highly structured samples are available. Furthermore, the formation of p/n
junctions on structured surfaces is possible by a variety of doping techniques,
in large part transferred from microelectronic circuit technology. The right
choice of doping method, to achieve good control of junction depth and doping
level, can contribute to an improvement of the overall efficiency that can be
obtained in devices for energy applications. A review of the state-of-the-art of
the fabrication and doping of silicon micro and nanopillars is presented here, as
well as of the analysis of the properties and geometry of thus-formed 3D
structured p/n junctions.
PMID- 26436659
TI - Phosphorylation of Threonine 794 on Tie1 by Rac1/PAK1 Reveals a Novel
Angiogenesis Regulatory Pathway.
AB - The endothelial receptor tyrosine kinase (RTK) Tie1 was discovered over 20 years
ago, yet its precise function and mode of action remain enigmatic. To shed light
on Tie1's role in endothelial cell biology, we investigated a potential threonine
phosphorylation site within the juxtamembrane domain of Tie1. Expression of a non
phosphorylatable mutant of this site (T794A) in zebrafish (Danio rerio)
significantly disrupted vascular development, resulting in fish with stunted and
poorly branched intersomitic vessels. Similarly, T794A-expressing human umbilical
vein endothelial cells formed significantly shorter tubes with fewer branches in
three-dimensional Matrigel cultures. However, mutation of T794 did not alter Tie1
or Tie2 tyrosine phosphorylation or downstream signaling in any detectable way,
suggesting that T794 phosphorylation may regulate a Tie1 function independent of
its RTK properties. Although T794 is within a consensus Akt phosphorylation site,
we were unable to identify a physiological activator of Akt that could induce
T794 phosphorylation, suggesting that Akt is not the physiological Tie1-T794
kinase. However, the small GTPase Ras-related C3 botulinum toxin substrate 1
(Rac1), which is required for angiogenesis and capillary morphogenesis, was found
to associate with phospho-T794 but not the non-phosphorylatable T794A mutant.
Pharmacological activation of Rac1 induced downstream activation of p21-activated
kinase (PAK1) and T794 phosphorylation in vitro, and inhibition of PAK1 abrogated
T794 phosphorylation. Our results provide the first demonstration of a signaling
pathway mediated by Tie1 in endothelial cells, and they suggest that a novel
feedback loop involving Rac1/PAK1 mediated phosphorylation of Tie1 on T794 is
required for proper angiogenesis.
PMID- 26436661
TI - Visceral Pain and Psychiatric Disorders.
AB - The high comorbidity existing between visceral pain and psychiatric disorders
such as depression and anxiety is well documented and it is gaining increasing
interest among scientists. When visceral pain and psychiatric disorders are
comorbid, they present a more debilitating condition than each disorder alone,
impacting significantly on the quality of life of these patients. Despite several
groups having shown that an overlapping pathophysiology exists between visceral
pain and stress-related disorders the link between them is not clear yet.
Moreover, it still remains to be elucidated if psychiatric conditions predispose
the individual to develop visceral hypersensitivity or vice versa. The brain-gut
microbiome axis is the bidirectional communication between the CNS and the
gastrointestinal tract. Alterations at different levels of this axis have been
implicated in both visceral hypersensitivity and psychiatric disorders. Here we
give an overview of what it is known about comorbid visceral pain and psychiatric
disorders and provide evidence of potential overlapping pathophysiological
mechanisms involved. Preclinical models of comorbid visceral pain and stress
related disorders are also discussed.
PMID- 26436662
TI - Correction: Fractal Feature of Particle-Size Distribution in the Rhizospheres and
Bulk Soils during Natural Recovery on the Loess Plateau, China.
PMID- 26436663
TI - Sclerosing Mesenteritis Presenting as a Pseudotumor of the Greater Omentum.
AB - OBJECTIVE: The aim was to demonstrate a diagnostic challenge of sclerosing
mesenteritis initially considered as liposarcoma. CLINICAL PRESENTATION AND
INTERVENTION: A 45-year-old man was admitted with a painful abdominal mass.
Abdominal computed tomography demonstrated a well- demarcated tumor in his left
hemiabdomen, with a large fat component and areas of soft tissue attenuation
suggestive of liposarcoma. Intraoperative findings showed a tumor arising from
the greater omentum. The tumor was completely removed, and histopathology
confirmed a pseudotumorous type of sclerosing mesenteritis with dominant
mesenteric lipodystrophy. CONCLUSION: This case showed that a pseudotumorous type
of sclerosing mesenteritis should be considered in the differential diagnosis of
the mesenteric tumors.
PMID- 26436665
TI - Regional variations in US cancer imaging data: a warning for imaging overuse.
AB - Danil V Makarov speaks to Gemma Westcott, Commissioning Editor: Danil V Makarov
is an Assistant Professor and Director of Surgical Research in the Department of
Urology at NYU Langone Medical Center (NY, USA). In addition, he is an Assistant
Professor in the Department of Population Health. His clinical areas of expertise
include prostate cancer, benign prostatic hyperplasia, erectile dysfunction,
kidney cancer, urinary tract infections, genitourinary neoplasm, elevated
prostate-specific antigen and testicular cancer. In addition, his research
interests are in the areas of prostate cancer, health policy and quality of care.
An alumnus of the Johns Hopkins University School of Medicine (MD, USA), he
completed his residency in urology at Johns Hopkins Hospital and a research
fellowship at Yale University School of Medicine (CT, USA).
PMID- 26436666
TI - Systematic review of effects of current transtibial prosthetic socket designs
Part 1: Qualitative outcomes.
AB - This review is an attempt to untangle the complexity of transtibial prosthetic
socket fit, determine the most important characteristic for a successful fitting,
and perhaps find some indication of whether a particular prosthetic socket type
might be best for a given situation. Further, it is intended to provide
directions for future research. We followed the PRISMA (Preferred Reporting Items
for Systematic Reviews and Meta-Analyses) guidelines and used medical subject
headings and standard key words to search for articles in relevant databases. No
restrictions were made on study design or type of outcome measure. From the
obtained search results (n = 1,863), 35 articles were included. The relevant data
were entered into a predefined data form that incorporated the Downs and Black
risk of bias assessment checklist. Results for the qualitative outcomes (n = 19
articles) are synthesized. Total surface bearing sockets lead to greater activity
levels and satisfaction in active persons with amputation, those with a traumatic
cause of amputation, and younger persons with amputation than patellar tendon
bearing sockets. Evidence on vacuum-assisted suction and hydrostatic sockets is
inadequate, and further studies are much needed. To improve the scientific basis
for prescription, comparison of and correlation between mechanical properties of
interface material, socket designs, user characteristics, and outcome measures
should be conducted and reported in future studies.
PMID- 26436664
TI - Purification and Characterization of Recombinant N-Terminally Pyroglutamate
Modified Amyloid-beta Variants and Structural Analysis by Solution NMR
Spectroscopy.
AB - Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is
characterized by memory loss and cognitive decline. Pathological hallmark of AD
brains are intracellular neurofibrillary tangles and extracellular amyloid
plaques. The major component of these plaques is the highly heterogeneous amyloid
beta (Abeta) peptide, varying in length and modification. In recent years
pyroglutamate-modified amyloid-beta (pEAbeta) peptides have increasingly moved
into the focus since they have been described to be the predominant species of
all N-terminally truncated Abeta. Compared to unmodified Abeta, pEAbeta is known
to show increased hydrophobicity, higher toxicity, faster aggregation and beta
sheet stabilization and is more resistant to degradation. Nuclear magnetic
resonance (NMR) spectroscopy is a particularly powerful method to investigate the
conformations of pEAbeta isoforms in solution and to study peptide/ligand
interactions for drug development. However, biophysical characterization of
pEAbeta and comparison to its non-modified variant has so far been seriously
hampered by the lack of highly pure recombinant and isotope-enriched protein.
Here we present, to our knowledge, for the first time a reproducible protocol for
the production of pEAbeta from a recombinant precursor expressed in E. coli in
natural isotope abundance as well as in uniformly [U-15N]- or [U-13C, 15N]
labeled form, with yields of up to 15 mg/l E. coli culture broth. The chemical
state of the purified protein was evaluated by RP-HPLC and formation of
pyroglutamate was verified by mass spectroscopy. The recombinant pyroglutamate
modified Abeta peptides showed characteristic sigmoidal aggregation kinetics as
monitored by thioflavin-T assays. The quality and quantity of produced pEAbeta40
and pEAbeta42 allowed us to perform heteronuclear multidimensional NMR
spectroscopy in solution and to sequence-specifically assign the backbone
resonances under near-physiological conditions. Our results suggest that the
presented method will be useful in obtaining cost-effective high-quality
recombinant pEAbeta40 and pEAbeta42 for further physiological and biochemical
studies.
PMID- 26436667
TI - Franck-Condon-like Progressions in Infrared Spectra of Biological Molecules.
AB - Infrared spectra in the NH stretch region are often used for structure
determination of gas-phase biological molecules. Vibrational couplings complicate
the structure determination process by giving rise to additional vibrational
bands along with the expected fundamental transitions. We present an example of a
strong anharmonic coupling in a biological molecule, Ac-Phe-Ala-LysH(+), which
causes the appearance of long vibrational progressions in the infrared spectrum.
By analyzing the spectra of the ground and the electronically excited state, we
determined that the coupling occurs between the NH stretch (omegaNH) and a low
frequency torsion of the phenyl ring (omegatau). We describe the vibrational
progressions using a Born-Oppenheimer-like separation of the high-frequency
stretch and low-frequency torsion with a quartic Taylor expansion for the
potential energy surface that accounts for the equilibrium distance and frequency
change of the torsional vibration upon the NH stretch excitation. We also
demonstrate that small conformational changes in the peptide are sufficient to
break this coupling.
PMID- 26436668
TI - Validating chest MRI to detect and monitor cystic fibrosis lung disease in a
pediatric cohort.
AB - BACKGROUND: Computed Tomography (CT) is the gold standard to assess
bronchiectasis and trapped air in cystic fibrosis (CF) lung disease, but has the
disadvantage of radiation exposure. Magnetic Resonance Imaging (MRI) is a
radiation free alternative. OBJECTIVE: To validate MRI as outcome measure by:
correlating MRI scores for bronchiectasis and trapped air with clinical
parameters, and by comparing those MRI scores with CT scores. METHODS: In
patients with CF (aged 5.6-17.4 years), MRI and CT were alternated annually
during routine annual check-ups between July 2007 and January 2010. Twenty-three
children had an MRI performed 1 year prior to CT, 34 children had a CT 1 year
prior to MRI. Bronchiectasis and trapped air were scored using the CF-MRI and CF
CT scoring system. CF-MRI scores were correlated with clinical parameters: FEV1 ,
Pseudomonas aeruginosa, pulmonary exacerbations and patient-reported respiratory
symptoms measured on the Cystic Fibrosis Questionnaire-Revised (CFQ-R), using
Spearman's correlation coefficient. MRI and CT scores were compared using intra
class correlation coefficients (ICC) and Bland-Altman plots. RESULTS: Fifty-seven
patients who had an MRI, CT and CFQ-R during the study period were included. CF
MRI bronchiectasis correlated with FEV1 , Pseudomonas aeruginosa, pulmonary
exacerbations and patient-reported respiratory symptoms. CF-MRI trapped air only
correlated with FEV1 and Pseudomonas aeruginosa. ICCs between MRI and CT
bronchiectasis and trapped air were 0.41 and 0.35 respectively. MRI tended to
overestimate bronchiectasis compared to CT. CONCLUSION: The associations between
CF-MRI scores and several important clinical parameters further contributes to
the validation of MRI. MRI provides different information than CT.
PMID- 26436669
TI - Aggregation of Cricket Activity in Response to Resource Addition Increases Local
Diversity.
AB - Crickets are often found feeding on fallen fruits among forest litter. Fruits and
other sugar-rich resources are not homogeneously distributed, nor are they always
available. We therefore expect that crickets dwelling in forest litter have a
limited supply of sugar-rich resource, and will perceive this and displace
towards resource-supplemented sites. Here we evaluate how sugar availability
affects cricket species richness and abundance in old-growth Atlantic forest by
spraying sugarcane syrup on leaf litter, simulating increasing availability, and
collecting crickets via pitfall trapping. We found an asymptotic positive
association between resource addition and species richness, and an interaction
between resource addition and species identity on cricket abundance, which
indicates differential effects of resource addition among cricket species. Our
results indicate that 12 of the 13 cricket species present in forest litter are
maintained at low densities by resource scarcity; this highlights sugar-rich
resource as a short-term driver of litter cricket community structure in tropical
forests. When resource was experimentally increased, species richness increased
due to behavioral displacement. We present evidence that the density of many
species is limited by resource scarcity and, when resources are added, behavioral
displacement promotes increased species packing and alters species composition.
Further, our findings have technical applicability for increasing sampling
efficiency of local cricket diversity in studies aiming to estimate species
richness, but with no regard to local environmental drivers or species-abundance
characteristics.
PMID- 26436673
TI - A mixed treatment comparison for short- and long-term outcomes of bare-metal and
drug-eluting coronary stents.
AB - BACKGROUND: The increasing use of drug eluting stents in interventional
cardiology calls for assessment of their efficacy and safety, both among drug
eluting and bare-metal stents, in the context of rational decision making.
METHODS: We searched for papers that compared any of the sirolimus-eluting stent,
paclitaxel-eluting stent, drug- eluting stent, biodegradable stent, everolimus
eluting stent, zotarolimus-resolute eluting stent, biolimus- eluting stent, bare
metal stent and zotarolimus-eluting stent. The search was contacted through
Medline, the Cochrane database, Embase, TCTMD, ClinicalTrials.gov, Clinical Trial
Results, CardioSource, abstracts and presentations from major cardiovascular
meetings. We also searched for further articles cited by selected papers.
Furthermore, important conferences and relevant proceedings and abstracts, such
as the American Heart Association, American College of Cardiology, Transcatheter
Cardiovascular Therapeutics, Society of Cardiovascular Angiography and
Intervention, European Society of Cardiology, and Euro-PCR, were also searched.
Inclusion criteria were: randomised controlled trials (RCTs), size of study
(>=100 patients), duration more than 6 months and definition of reported
endpoints (target vessel revascularization, thrombosis, myocardial infarction and
cardiac death). Analysis of the data was performed for short-term (less than a
year) and long-term outcomes (more than a year). A mixed treatment comparison
approach was utilised for the data analysis. CONCLUSIONS: Based on the rankings
of each treatment, a distinct difference between the 2nd and 1st generation
stents was identified. We can conclude that everolimus, zotarolimus-resolute and
biolimus eluting stents carry the highest probabilities of being superior for all
endpoints.
PMID- 26436672
TI - Attenuation of reflected waves in man during retrograde propagation from femoral
artery to proximal aorta.
AB - BACKGROUND: Wave reflection may be an important influence on blood pressure, but
the extent to which reflections undergo attenuation during retrograde propagation
has not been studied. We quantified retrograde transmission of a reflected wave
created by occlusion of the left femoral artery in man. METHODS: 20 subjects (age
31-83 years; 14 male) underwent invasive measurement of pressure and flow
velocity with a sensor-tipped intra-arterial wire at multiple locations distal to
the proximal aorta before, during and following occlusion of the left femoral
artery by thigh cuff inflation. A numerical model of the circulation was also
used to predict reflected wave transmission. Wave reflection was measured as the
ratio of backward to forward wave energy (WRI) and the ratio of peak backward to
forward pressure (Pb/Pf). RESULTS: Cuff inflation caused a marked reflection
which was largest at 5-10 cm from the cuff (change (Delta) in WRI=0.50 (95% CI
0.38, 0.62); p<0.001, DeltaPb/Pf=0.23 (0.18-0.29); p<0.001). The magnitude of the
cuff-induced reflection decreased progressively at more proximal locations and
was barely discernible at sites>40 cm from the cuff including in the proximal
aorta. Numerical modelling gave similar predictions to those observed
experimentally. CONCLUSIONS: Reflections due to femoral artery occlusion are
markedly attenuated by the time they reach the proximal aorta. This is due to
impedance mismatches of bifurcations traversed in the backward direction. This
degree of attenuation is inconsistent with the idea of a large discrete reflected
wave arising from the lower limb and propagating back into the aorta.
PMID- 26436674
TI - Personalized ADP-receptor inhibition strategy and outcomes following primary PCI
for STEMI (PASTOR study).
AB - BACKGROUND: Adequate antiplatelet therapy in patients with myocardial infarction
with ST-elevation (STEMI) is vital in order to avoid ischemic complications.
However, especially with the novel potent oral drugs, bleeding is a major
concern. We aimed to investigate whether STEMI patients switched to novel ADP
receptor inhibitors due to high platelet reactivity (HPR) on clopidogrel have
similar outcomes compared to patients with adequate response to clopidogrel.
METHODS: A prospective cohort of 175 STEMI patients (mean age 62.3 years)
undergoing primary PCI were included in the PASTOR study. Patients were loaded
with 600 mg clopidogrel before the index PCI procedure. Bedside VerifyNow P2Y12
platelet function testing was performed the following morning. RESULTS: 46
patients (26.3%) were found to have HPR on clopidogrel (PRU>235) and were
switched to novel ADP receptor antagonists. The remaining 129 patients were
treated with clopidogrel. The mean duration of dual antiplatelet therapy (DAPT)
was 6.7 months. Duration of entire follow-up of patients was approximately 2
years. Major adverse cardiac events (MACE) while patients were on DAPT occurred
in 7.0% in the clopidogrel group compared to 8.7% in the novel ADP receptor
antagonist group (p=0.70). No differences were observed between groups off-DAPT
either. CONCLUSIONS: Following primary PCI for STEMI, patients with adequate
response to clopidogrel show similar outcomes compared to patients switched to
novel ADP receptor antagonists due to HPR on clopidogrel. Platelet reactivity
testing can be used to guide the choice of antiplatelet therapy in patients with
STEMI treated by primary PCI.
PMID- 26436670
TI - Oral TNFalpha Modulation Alters Neutrophil Infiltration, Improves Cognition and
Diminishes Tau and Amyloid Pathology in the 3xTgAD Mouse Model.
AB - Cytokines such as TNFalpha can polarize microglia/macrophages into different
neuroinflammatory types. Skewing of the phenotype towards a cytotoxic state is
thought to impair phagocytosis and has been described in Alzheimer's Disease
(AD). Neuroinflammation can be perpetuated by a cycle of increasing cytokine
production and maintenance of a polarized activation state that contributes to AD
progression. In this study, 3xTgAD mice, age 6 months, were treated orally with 3
doses of the TNFalpha modulating compound isoindolin-1,3 dithione (IDT) for 10
months. We demonstrate that IDT is a TNFalpha modulating compound both in vitro
and in vivo. Following long-term IDT administration, mice were assessed for
learning & memory and tissue and serum were collected for analysis. Results
demonstrate that IDT is safe for long-term treatment and significantly improves
learning and memory in the 3xTgAD mouse model. IDT significantly reduced paired
helical filament tau and fibrillar amyloid accumulation. Flow cytometry of brain
cell populations revealed that IDT increased the infiltrating neutrophil
population while reducing TNFalpha expression in this population. IDT is a safe
and effective TNFalpha and innate immune system modulator. Thus small molecule,
orally bioavailable modulators are promising therapeutics for Alzheimer's
disease.
PMID- 26436675
TI - Selection of the appropriate binary effect measure for the correct interpretation
in meta-analysis.
PMID- 26436676
TI - Impact of intraprocedural thrombotic events on short- and long-term outcomes
following percutaneous coronary intervention. Evidence from a meta-analysis.
AB - BACKGROUND: Data regarding the effects of intraprocedural thrombotic events
(IPTE) are scarce. Hence we aim to perform a meta-analysis to examine the
outcomes of IPTE compared to non-IPTE during PCI. METHODS: We performed a
literature search of all published full-length articles of studies that reported
data on patients with IPTE compared with non-IPTE during PCI. We calculated odd
ratios via random effects model. RESULTS: A total of 26,697 patients, of which
1572 patients had IPTE, were included in this analysis. In-hospital, IPTE was
associated with higher mortality (odds ratio (OR) 5.36, 95% confidence interval
(CI) [2.31, 12.41]; p<0.0001), myocardial infarction (MI) and major bleeding
compared to non-IPTE. At 30 days, IPTE was also associated with higher mortality
(OR 4.57, 95% CI [2.43, 8.60]; p<0.0001), MI, repeat revascularization, stent
thrombosis and major bleeding compared to non-IPTE group. IPTE was also
associated with higher long-term mortality (OR 2.19, 95% CI [1.35, 3.53];
p=0.001). Among IPTE patients, intraprocedural stent thrombosis was associated
with greater odds of MI compared to both no reflow and distal embolization
events. CONCLUSION: IPTE during PCI is associated with more adverse ischemic
events, including mortality, during the index hospitalization, at 30 days and
long-term.
PMID- 26436677
TI - Full-Arch, Implant-Supported Monolithic Zirconia Rehabilitations: Pilot Clinical
Evaluation of Wear Against Natural or Composite Teeth.
AB - PURPOSE: To clinically evaluate the amount of contact wear generated between full
arch monolithic zirconia implant-supported restorations and natural or composite
antagonists, over a 1-year period. MATERIALS AND METHODS: Forty-seven teeth from
clinically functional, full-arch monolithic zirconia screw-retained implant
prostheses (FDPs) and their antagonists were investigated. The first group
("Zirconia-E") was opposed to natural teeth ("Enamel"), whereas the other one
("Zirconia-CR") was opposed to nano-hybrid composite teeth ("Composite Resin").
Replicas of the restorations and their antagonists were obtained immediately
after delivery (T0 ) and after 1 year of clinical service (T1 ). Each tooth
surface was individually evaluated three-dimensionally by software to quantify
the vertical distance between the two scans (Hausdorff distance), which was
considered as contact wear. Data obtained for each arch were subjected to one-way
ANOVA test and a post hoc analysis (Tukey's test) at a 5% level of significance.
Furthermore, the influence of the location of the teeth (anterior or posterior)
was analyzed. Minimum post hoc statistical power between statistically different
groups was 99.6%. RESULTS: Mean values were 63 +/- 23 MUm for Zirconia-E, 76 +/-
29 MUm for enamel, 70 +/- 38 MUm for composite resin; Zirconia-CR had a mean
value of 19 +/- 4 MUm and significantly differed from the other groups. Contact
wear between anterior and posterior teeth differed significantly only in the
composite resin arch, with a mean of 39 +/- 22 MUm for anterior teeth versus 101
+/- 19 MUm for posterior ones. CONCLUSIONS: Within the limitations of this
preliminary evaluation, monolithic zirconia full-arch rehabilitations induced a
clinically acceptable wear on natural and composite antagonists over a 1-year
period; they might be considered a viable solution for implant-supported
rehabilitations.
PMID- 26436680
TI - Temperature Determination by EPR at 275 GHz and the Detection of Temperature
Jumps in Aqueous Samples.
AB - Second-moment analysis along two dimensions of continuous-wave EPR spectra of
nitroxides enables EPR thermometry in a broad temperature range. Simulations show
that the temperature can be derived in both the slow-motion and the fast-motion
regime, which is experimentally verified at 275 GHz for H2O/glycerol (50/50% by
volume) and pure water. We demonstrate that this tool allows the calibration of
temperature jumps induced by infrared laser irradiation of a submicroliter sample
in the single-mode cavity of a 275 GHz spectrometer, which prepares for kinetic
studies of processes involving paramagnetic species.
PMID- 26436678
TI - Course of Chronic Trypanosoma cruzi Infection after Treatment Based on
Parasitological and Serological Tests: A Systematic Review of Follow-Up Studies.
AB - BACKGROUND: Chagas disease is caused by the flagellate protozoan Trypanosoma
cruzi (T. cruzi). It is endemic in Latin American countries outside the
Caribbean. The current criterion for cure in the chronic phase of the disease is
the negativization of at least two serological tests such as enzyme-linked
immunosorbent assay (ELISA), indirect immunofluorescence assay (IIF) and indirect
hemagglutination assay (IHA). The serological evolution of treated subjects with
chronic T. cruzi infection is variable. Treatment failure is indicated by a
positive parasitological and/or molecular test (persistence of parasitemia).
OBJECTIVES: To summarize the pattern of response to treatment of parasitological,
molecular and serological tests performed during the follow-up of subjects with
chronic T. cruzi infection. METHODS: Electronic searches in relevant databases
and screening of citations of potentially eligible articles were accomplished.
Organizations focusing on neglected infectious diseases were asked for help in
identifying relevant studies. Included studies were randomized controlled trials
(RCTs), quasi-RCTs, and cohort studies involving adults and children with chronic
infection who received trypanocidal treatment (benznidazole or nifurtimox) and
were followed over time. The assessment of risk of bias was performed separately
for each study design. The Cochrane Collaboration's tool and the guidelines
developed by Hayden et al. were used. Two reviewers extracted all data
independently. A third review author was consulted in case of discordant opinion.
Additional analyses were defined in ad-hoc basis. Scatter plots for percentage of
positive parasitological and molecular tests and for negative serological tests
were developed by using the lowess curve technique. Heterogeneity was measured by
I2. The protocol was registered in PROSPERO, an international prospective
register of systematic review protocols (Registration Number CRD42012002162).
RESULTS: Out of 2,136 citations screened, 54 studies (six RCTs and 48 cohort
studies) were included. The smoothed curves for positive xenodiagnosis and
positive polymerase chain reaction (PCR) were characterized by a sharp decrease
at twelve month posttreatment. Afterwards, they reached 10-20% and 40% for
xenodiagnosis and PCR, respectively. The smoothed curves for negative
conventional serological tests increased up to 10% after 48 months of treatment.
In the long-term, the rate of negativization was between 20% and 45%. The main
sources of bias identified across cohort studies were the lack of control for
confounding and attrition bias. In general, RCTs were judged as low risk of bias
in all domains. The level of heterogeneity across included studies was moderate
to high. Additional analysis were incomplete because of the limited availability
of data. In this regard, the country of origin of study participants might affect
the results of parasitological and molecular tests, while the level of risk of
bias might affect serological outcomes. Subgroup analysis suggested that
seronegativization occurs earlier in children compared to adults. CONCLUSIONS: We
acknowledge that there is a dynamic pattern of response based on parasitological,
molecular and serological tests in subjects chronically infected with T. cruzi
after treatment. Our findings suggest a trypanocidal effect in the long-term
follow-up. Further research is needed to explore potential sources of
heterogeneity and to conduct reliable subgroup analysis.
PMID- 26436679
TI - Wheat leaf lipids during heat stress: I. High day and night temperatures result
in major lipid alterations.
AB - Understanding how wheat (Triticum aestivum L.) plants under high temperature (HT)
regulate lipid composition is critical to developing climate-resilient varieties.
We measured 165 glycerolipids and sterol derivatives under optimum and high day
and night temperatures in wheat leaves using electrospray ionization-tandem mass
spectrometry. Levels of polar lipid fatty acyl chain unsaturation were lower in
both heat-tolerant genotype Ventnor and susceptible genotype Karl 92 under HT,
compared with optimum temperature. The lower unsaturation was predominantly
because of lower levels of 18:3 acyl chains and higher levels of 18:1 and 16:0
acyl chains. Levels of 18:3-containing triacylglycerols increased threefold/more
under HT, consistent with their possible role in sequestering fatty acids during
membrane lipid remodelling. Phospholipids containing odd-numbered or oxidized
acyl chains accumulated in leaves under HT. Sterol glycosides (SG) and 16:0
acylated sterol glycosides (ASG) were higher under HT than optimum temperatures.
Ventnor had lower amounts of phospholipids with oxidized acyl chains under HT and
higher amounts of SG and 16:0-ASG than Karl 92. Taken together, the data
demonstrate that wheat leaf lipid composition is altered by HT, in which some
lipids are particularly responsive to HT, and that two wheat genotypes, chosen
for their differing physiological responses to HT, differ in lipid profile under
HT.
PMID- 26436681
TI - Complete mitochondrial genome and phylogenic analysis of the mudskipper
Scartelaos gigas (Perciformes, Gobiidae).
AB - In this paper, the complete mitochondrial genome sequence of Scartelaos gigas was
firstly determined. The circular genome (16 717 bp) comprises 13 protein-coding
genes, 22 tRNA genes, 2 rRNA genes, and 1 control region. The overall base
composition of S. gigas is 28.9% for C, 28.3% for A, 26.4% for T, 16.4% for G,
with a slight A + T bias of 54.7%. In the control region, the termination
associated sequence and conserved sequence block domains were found, but the
tandem repeat structure was not found. It has the typical vertebrate
mitochondrial gene arrangement. The phylogenic analysis using the Neighbor
Joining method showed that the fishes belonging to Gobiidae, Odontoburidae, and
Eleotridae formed three branches grouped with other fishes into one clade which
separated from the mammals. We hope that the results from the present study will
provide useful molecular information for the further studies on genetic structure
and demographic history of S. gigas.
PMID- 26436682
TI - Patterns of sun protective behaviors among Hispanic children in a skin cancer
prevention intervention.
AB - BACKGROUND: Invasive melanoma is becoming more common in U.S. Hispanics, yet
little is known about the sun protection behaviors in this population,
particularly children and adolescents who incur high ultraviolet (UV) exposures.
METHODS: We used latent class analysis to examine patterns of sun protective
behaviors in a cross-sectional survey of Hispanic elementary students
participating in a sun safety intervention in Los Angeles from 2013- to 2014
(N=972). Five behavior indicators in two environments (school and home)
representing multiple methods of sun protection were selected for the model.
RESULTS: Results suggested a four-class model best fit the data. Classes were
labeled in order of increasing risk as multiple protective behaviors (28%),
clothing and shade (32%), pants only (15%), and low/inconsistent protective
behaviors (25%). Children who reported high parental engagement with sun
protection were significantly more likely to be classified in high overall
protective categories (odds ratio (OR)=4.77). Girls were more likely than boys to
be classified in the highest protecting class (OR=3.46), but were also more
likely to be in the "pants only" class (OR=2.65). Sensitivity to sunburn was
associated with less likelihood of being in the "clothing and shade" class
(OR=0.53). CONCLUSION: The differences among these classes and their predictors
reveal the heterogeneity and complexity of Hispanic children's sun protective
behaviors. These findings have implications for the design and delivery of future
sun protection interventions targeting Hispanic children, as strategies tailored
to specific subgroups may be more effective in achieving meaningful behavioral
changes.
PMID- 26436683
TI - Effects of a multi-component camp-based intervention on inflammatory markers and
adipokines in children: A randomized controlled trial.
AB - OBJECTIVE: To examine the effects of a multi-component camp-based intervention on
inflammatory markers and adipokines in children. METHODS: One hundred and fifteen
children were recruited in Odense, Denmark (2012-2014). The participants were
randomly allocated to either the day camp intervention arm (DCIA) or the standard
intervention arm (SIA). The intervention for the DCIA consisted of a 6-week camp
based intervention and a 46-week family-based intervention. The SIA was offered
one weekly physical activity session for 6 weeks and one educational meeting. C
reactive protein (CRP), monocyte chemoattractant protein-1 (MCP1), leptin, and
adiponectin were measured in serum at baseline, 6 weeks and 52 weeks. RESULTS: In
comparison with the SIA, the reductions in CRP (P=0.003) and leptin (p<0.001)
were larger in the DCIA at 6 weeks. The intervention effects on leptin were
significantly mediated by the changes in body fat mass. No intervention effects
on CRP and leptin were seen at 52 weeks. No between-group differences in changes
in MCP1 and adiponectin were observed at 6 weeks or 52 weeks. CONCLUSIONS: The 6
week camp intervention resulted in reductions in CRP and leptin. The intervention
effects did not persist to 52 weeks. The intervention effect on leptin was
explained by changes in body fat mass.
PMID- 26436684
TI - Smoking, heavy drinking, and depression among U.S. middle-aged and older adults.
AB - OBJECTIVE: To examine the relationship between smoking, heavy drinking and
depression among U.S. middle-aged and older adults. METHOD: Individual-level data
came from 1992-2012 waves of the Health and Retirement Study. Smoking was
ascertained from self-reported cigarette smoking status at the time of interview.
Heavy drinking was defined as one or more drinks per day on average or four or
more drinks on any occasion in the past three months for women, and two or more
drinks per day on average or four or more drinks on any occasion in the past
three months for men. Depression was defined as scoring three and above on the
eight-item Center for Epidemiologic Studies Depression Scale. Cox proportional
hazards regressions were performed to examine the relationship between smoking,
heavy drinking and depression. RESULTS: Compared to non-smokers, smokers free
from depression and heavy drinking at baseline were 20% (95% confidence interval:
12-28%) and 34% (20-50%) more likely to develop depression and engage in heavy
drinking during follow-up period, respectively. Compared to non-depressed
participants, participants with depression who were nonsmokers and non-heavy
drinkers at baseline were 41% (14-74%) and 18% (6-31%) more likely to smoke and
engage in heavy drinking during follow-up, respectively. Compared to non-heavy
drinkers, heavy drinkers who were nonsmokers at baseline were 60% (26-104%) more
likely to smoke during follow-up. CONCLUSION: Health promotion programs in
midlife and older age should be mindful of the associations between smoking,
heavy drinking and depression in order to improve intervention effectiveness.
PMID- 26436685
TI - Smoking-attributable medical expenditures: Time biases and smokers' social role.
PMID- 26436687
TI - Brainstem node for loss of consciousness due to GABA(A) receptor-active
anesthetics.
AB - The molecular agents that induce loss of consciousness during anesthesia are
classically believed to act by binding to cognate transmembrane receptors widely
distributed in the CNS and critically suppressing local processing and network
connectivity. However, previous work has shown that microinjection of anesthetics
into a localized region of the brainstem mesopontine tegmentum (MPTA) rapidly and
reversibly induces anesthesia in the absence of global spread. This implies that
functional extinction is determined by neural pathways rather than vascular
distribution of the anesthetic agent. But does clinical (systemic-induced)
anesthesia employ MPTA-linked circuitry? Here we show that cell-selective
lesioning of the MPTA in rats does not, in itself, induce anesthesia or coma.
However, it increases the systemic dose of pentobarbital required to induce
anesthesia, in a manner proportional to the extent of the lesion. Such lesions
also affect emergence, extending the duration of anesthesia. Off-target and sham
lesions were ineffective. Combined with the prior microinjection data, we
conclude that drug delivery to the MPTA is sufficient to induce loss-of
consciousness and that neurons in this locus are necessary for anesthetic
induction at clinically relevant doses. Together, the results support an
architecture for anesthesia with the MPTA serving as a key node in an endogenous
network of dedicated pathways that switch between wake and unconsciousness. As
such, the MPTA might also play a role in syncope, concussion and sleep.
PMID- 26436688
TI - High Cycling Stability and Extreme Rate Performance in Nanoscaled LiMn2O4 Thin
Films.
AB - Ultrathin LiMn2O4 electrode layers with average crystal size of ~15 nm were
fabricated by means of radio frequency sputtering. Cycling behavior and rate
performance was evaluated by galvanostatic charge and discharge measurements. The
thinnest films show the highest volumetric capacity and best cycling stability,
retaining the initial capacity over 70 (dis)charging cycles when manganese
dissolution is prevented. The increased stability for film thicknesses below 50
nm allows cycling in both the 4 and 3 V potential regions, resulting in a high
volumetric capacity of 1.2 Ah/cm3. It is shown that the thinnest films can be
charged to 75% of their full capacity within 18 s (200 C), the best rate
performance reported for LiMn2O4. This is explained by the short diffusion
lengths inherent to thin films and the absence of phase transformation.
PMID- 26436686
TI - Gender differences in incidence and outcomes of urothelial and kidney cancer.
AB - A gender discrepancy exists in the incidence of both urothelial and kidney
carcinomas, with more men presenting with these cancers than women. Men have a
threefold greater risk of developing bladder cancer than women, but female gender
has been identified as an independent adverse prognostic factor for both
recurrence and progression of this disease. In particular, women with bladder
cancer are often diagnosed with a higher tumour stage than men. Conclusive data
on the influence of gender on outcomes of patients with upper tract urothelial
carcinoma are currently lacking, although men seem to have a higher disease
incidence, whereas survival outcomes might be independent of gender. Patients
with renal cell carcinoma are more often men and they typically have larger
tumours and higher stage and grade disease than women with this cancer. Smoking
habits, tumour biology, occupational risk factors and sex steroid hormones and
their receptors could have a role in these observed gender disparities. The
majority of data support the theory that gender influences incidence and
prognosis of urothelial and kidney cancers; men and women are different
genetically and socially, making the consideration of gender a key factor in the
clinical decision-making process. Thus, the inclusion of this variable in
validated prognostic tables and nomograms should be discussed as a matter of
importance.
PMID- 26436689
TI - The safety of liposome bupivacaine 2 years post-launch: a look back and a look
forward.
AB - The need for better post-surgical pain management continues to be unmet, despite
clinicians' awareness and concern for many years. Opioids remain the standard of
care because of their analgesic efficacy; however, opioid use is often associated
with adverse effects and poor patient outcomes. Multimodal analgesic regimens
have recently been endorsed as a way to provide adequate post-surgical pain
control while reducing opioid consumption. Liposome bupivacaine is a liposomal
formulation of bupivacaine indicated for a single administration into the
surgical site. Based on the available clinical trial data compiled to date, as
well as the author's review of publicly available post-marketing safety
information, liposome bupivacaine may be a viable addition to currently available
therapeutic options for post-surgical analgesia while reducing potential risks
associated with use of opioid analgesics, and may represent a useful addition to
the multimodal analgesic modalities currently used for post-operative pain
management. The potential for its use in other areas is also being investigated.
The purpose of this review is to examine the currently available post-marketing
safety information on liposome bupivacaine.
PMID- 26436691
TI - Experiments on Ultrasonic Lubrication Using a Piezoelectrically-assisted
Tribometer and Optical Profilometer.
AB - Friction and wear are detrimental to engineered systems. Ultrasonic lubrication
is achieved when the interface between two sliding surfaces is vibrated at a
frequency above the acoustic range (20 kHz). As a solid-state technology,
ultrasonic lubrication can be used where conventional lubricants are unfeasible
or undesirable. Further, ultrasonic lubrication allows for electrical modulation
of the effective friction coefficient between two sliding surfaces. This property
enables adaptive systems that modify their frictional state and associated
dynamic response as the operating conditions change. Surface wear can also be
reduced through ultrasonic lubrication. We developed a protocol to investigate
the dependence of friction force reduction and wear reduction on the linear
sliding velocity between ultrasonically lubricated surfaces. A pin-on-disc
tribometer was built which differs from commercial units in that a piezoelectric
stack is used to vibrate the pin at 22 kHz normal to the rotating disc surface.
Friction and wear metrics including effective friction force, volume loss, and
surface roughness are measured without and with ultrasonic vibrations at a
constant pressure of 1 to 4 MPa and three different sliding velocities: 20.3,
40.6, and 87 mm/sec. An optical profilometer is utilized to characterize the wear
surfaces. The effective friction force is reduced by 62% at 20.3 mm/sec.
Consistently with existing theories for ultrasonic lubrication, the percent
reduction in friction force diminishes with increasing speed, down to 29%
friction force reduction at 87 mm/sec. Wear reduction remains essentially
constant (49%) at the three speeds considered.
PMID- 26436692
TI - Interparticle Forces Underlying Nanoparticle Self-Assemblies.
AB - Studies on the self-assembly of nanoparticles have been a hot topic in
nanotechnology for decades and still remain relevant for the present and future
due to their tunable collective properties as well as their remarkable
applications to a wide range of fields. The novel properties of nanoparticle
assemblies arise from their internal interactions and assemblies with the desired
architecture key to constructing novel nanodevices. Therefore, a comprehensive
understanding of the interparticle forces of nanoparticle self-assemblies is a
pre-requisite to the design and control of the assembly processes, so as to
fabricate the ideal nanomaterial and nanoproducts. Here, different categories of
interparticle forces are classified and discussed according to their origins,
behaviors and functions during the assembly processes, and the induced collective
properties of the corresponding nanoparticle assemblies. Common interparticle
forces, such as van der Waals forces, electrostatic interactions, electromagnetic
dipole-dipole interactions, hydrogen bonds, solvophonic interactions, and
depletion interactions are discussed in detail. In addition, new categories of
assembly principles are summarized and introduced. These are termed template
mediated interactions and shape-complementary interactions. A deep understanding
of the interactions inside self-assembled nanoparticles, and a broader
perspective for the future synthesis and fabrication of these promising
nanomaterials is provided.
PMID- 26436690
TI - Integrin endosomal signalling suppresses anoikis.
AB - Integrin-containing focal adhesions transmit extracellular signals across the
plasma membrane to modulate cell adhesion, signalling and survival. Although
integrins are known to undergo continuous endo/exocytic traffic, the potential
impact of endocytic traffic on integrin-induced signals is unknown. Here, we
demonstrate that integrin signalling is not restricted to cell-ECM adhesions and
identify an endosomal signalling platform that supports integrin signalling away
from the plasma membrane. We show that active focal adhesion kinase (FAK), an
established marker of integrin-ECM downstream signalling, localizes with active
integrins on endosomes. Integrin endocytosis positively regulates adhesion
induced FAK activation, which is early endosome antigen-1 and small GTPase Rab21
dependent. FAK binds directly to purified endosomes and becomes activated on
them, suggesting a role for endocytosis in enhancing distinct integrin downstream
signalling events. Finally, endosomal integrin signalling contributes to cancer
related processes such as anoikis resistance, anchorage independence and
metastasis.
PMID- 26436693
TI - "Healing is a Done Deal": Temporality and Metabolic Healing Among Evangelical
Christians in Samoa.
AB - Drawing on fieldwork in independent Samoa, in this article, I analyze the
temporal dimensions of evangelical Christian healing of metabolic disorders. I
explore how those suffering with metabolic disorders draw from multiple time
based notions of healing, drawing attention to the limits of biomedicine in
contrast with the effectiveness of Divine healing. By simultaneously engaging
evangelical and biomedical temporalities, I argue that evangelical Christians
create wellness despite sickness and, in turn, re-signify chronic suffering as a
long-term process of Christian healing. Positioning biomedical temporality and
evangelical temporality as parallel yet distinctive ways of practicing healing,
therefore, influences health care choices.
PMID- 26436694
TI - Changes in exposure temperature lead to changes in pesticide toxicity to
earthworms: A preliminary study.
AB - The occurring climate changes will have direct consequences to all ecosystems,
including the soil ecosystems. The effects of climate change include, among
other, the changes in temperature and greater frequency and intensity of extreme
weather conditions. Temperature is an important factor in ecotoxicological
investigations since it can act as a stressor and influence the physiological
status of organisms, as well as affect the fate and transport of pollutants
present in the environment. However, most of so far conducted (eco)toxicological
investigations neglected the possible effects of temperature and focused solely
on the effects of toxicants on organisms. Considering that temperature can
contribute to the toxicity of pollutants, it is of immense importance to
investigate whether the change in the exposure temperature will impact the
strength of the toxic effects of pollutants present in soil ecosystems.
Therefore, in the present study the toxicity of several commonly used pesticides
to earthworms was assessed under different exposure temperatures (15, 20 and 25
degrees C). The results showed that changes in exposure temperature lead to
changes in susceptibility of earthworms to particular pesticides. Namely,
exposures to the same pesticide concentration at different temperatures lead to
different toxicity responses. Increase in exposure temperature in most cases
caused increase in toxicity, whereas decrease in temperature mostly caused
decrease in toxicity. This preliminary study points to need for an in-depth
investigation of mechanisms by which temperature affects the toxicity of
pesticides and also provides important data for future research on the effects of
temperature change on the soil ecosystems.
PMID- 26436695
TI - Discovery of Compound A--a selective activator of the glucocorticoid receptor
with anti-inflammatory and anti-cancer activity.
AB - Glucocorticoids are among the most effective anti-inflammatory drugs, and are
widely used for cancer therapy. Unfortunately, chronic treatment with
glucocorticoids results in multiple side effects. Thus, there was an intensive
search for selective glucocorticoid receptor (GR) activators (SEGRA), which
retain therapeutic potential of glucocorticoids, but with fewer adverse effects.
GR regulates gene expression by transactivation (TA), by binding as homodimer to
gene promoters, or transrepression (TR), via diverse mechanisms including
negative interaction between monomeric GR and other transcription factors. It is
well accepted that metabolic and atrophogenic effects of glucocorticoids are
mediated by GR TA. Here we summarized the results of extensive international
collaboration that led to discovery and characterization of Compound A (CpdA), a
unique SEGRA with a proven "dissociating" GR ligand profile, preventing GR
dimerization and shifting GR activity towards TR both in vitro and in vivo. We
outlined here the unusual story of compound's discovery, and presented a
comprehensive overview of CpdA ligand properties, its anti-inflammatory effects
in numerous animal models of inflammation and autoimmune diseases, as well as its
anti-cancer effects. Finally, we presented mechanistic analysis of CpdA and
glucocorticoid effects in skin, muscle, bone, and regulation of glucose and fat
metabolism to explain decreased CpdA side effects compared to glucocorticoids.
Overall, the results obtained by our and other laboratories underline
translational potential of CpdA and its derivatives for treatment of
inflammation, autoimmune diseases and cancer.
PMID- 26436696
TI - A novel far-red fluorescent xenograft model of ovarian carcinoma for preclinical
evaluation of HER2-targeted immunotoxins.
AB - We have created a novel fluorescent model of a human ovarian carcinoma xenograft
overexpressing receptor HER2, a promising molecular target of solid tumors. The
model is based on a newly generated SKOV-kat cell line stably expressing far-red
fluorescent protein Katushka. Katushka is most suitable for the in vivo imaging
due to an optimal combination of high brightness and emission in the "window of
tissue transparency". The relevance of the fluorescent model for the in vivo
monitoring of tumor growth and response to treatment was demonstrated using a
newly created HER2-targeted recombinant immunotoxin based on the 4D5scFv antibody
and a fragment of the Pseudomonas exotoxin A.
PMID- 26436697
TI - c-Met inhibitors attenuate tumor growth of small cell hypercalcemic ovarian
carcinoma (SCCOHT) populations.
AB - A cellular model (SCCOHT-1) of the aggressive small cell hypercalcemic ovarian
carcinoma demonstrated constitutive chemokine and growth factor production
including HGF. A simultaneous presence of c-Met in 41% SCCOHT-1 cells suggested
an autocrine growth mechanism. Expression of c-Met was also observed at low
levels in the corresponding BIN-67 cell line (6.5%) and at high levels in ovarian
adenocarcinoma cells (NIH:OVCAR-3 (84.4%) and SK-OV-3 (99.3%)).
Immunohistochemistry of c-Met expression in SCCOHT tumors revealed a
heterogeneous distribution between undetectable levels and 80%. Further
characterization of SCCOHT-1 and BIN-67 cells by cell surface markers including
CD90 and EpCAM demonstrated similar patterns with differences to the ovarian
adenocarcinoma cells. HGF stimulation of SCCOHT-1 cells was associated with c-Met
phosphorylation at Tyr1349 and downstream Thr202/Tyr204 phosphorylation of p44/42
MAP kinase. This HGF-induced signaling cascade was abolished by the c-Met
inhibitor foretinib. Cell cycle analysis after foretinib treatment demonstrated
enhanced G2 accumulation and increasing apoptosis within 72 h. Moreover, the IC50
of foretinib revealed 12.4 nM in SCCOHT-1 cells compared to 411 nM and 481 nM in
NIH:OVCAR-3 and SK-OV-3 cells, respectively, suggesting potential therapeutic
effects. Indeed, SCCOHT-1 and BIN-67 tumor xenografts in NODscid mice exhibited
an approximately 10-fold and 5-fold reduced tumor size following systemic
application of foretinib, respectively. Furthermore, foretinib-treated tumors
revealed a significantly reduced vascularization and little if any c-Met-mediated
signal transduction. Similar findings of reduced proliferative capacity and
declined tumor size were observed after siRNA-mediated c-Met knock-down in SCCOHT
1 cells demonstrating that in vivo inhibition of these pathways contributed to an
attenuation of SCCOHT tumor growth.
PMID- 26436698
TI - Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results
from in vitro and in vivo studies with bromelain and N-acetylcysteine.
AB - Aberrant expression of membrane-associated and secreted mucins, as evident in
epithelial tumors, is known to facilitate tumor growth, progression and
metastasis, and to provide protection against adverse growth conditions,
chemotherapy and immune surveillance. Emerging evidence provides support for the
oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression
to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal
tumors, in particular increased or de novo expression of MUC2 and/or MUC5AC, is
widely believed to imply an adverse clinicopathological feature. Through
formation of viscous gels, too, MUC2 and MUC5AC significantly contribute to the
biology and pathogenesis of mucin-secreting gastrointestinal tumors. Here, we
investigated the mucin-depleting effects of bromelain (BR) and N-acetylcysteine
(NAC), in nine different regimens as single or combination therapy, in in vitro
(MKN45, KATOIII and LS174T cell lines) and in vivo (female nude mice bearing
intraperitoneal MKN45 and LS174T) settings. The inhibitory effects of the
treatment on cancer cell growth and proliferation were also evaluated in vivo.
Our results suggest that a combination of BR and NAC with dual effects on growth
and mucin products of mucin-expressing tumor cells is a promising candidate
towards the development of novel approaches to gastrointestinal malignancies with
the involvement of mucin pathology. This capability supports the use of this
combination formulation in locoregional approaches for reducing the adverse
effects of the aberrantly secreted gel-forming mucins, as in pseudomyxoma
peritonei and similar pathologies with ectopic production of mucin.
PMID- 26436699
TI - Identification of high risk anaplastic gliomas by a diagnostic and prognostic
signature derived from mRNA expression profiling.
AB - Anaplastic gliomas are characterized by variable clinical and genetic features,
but there are few studies focusing on the substratification of anaplastic
gliomas. To identify a more objective and applicable classification of anaplastic
gliomas, we analyzed whole genome mRNA expression profiling of four independent
datasets. Univariate Cox regression, linear risk score formula and receiver
operating characteristic (ROC) curve were applied to derive a gene signature with
best prognostic performance. The corresponding clinical and molecular information
were further analyzed for interpretation of the different prognosis and the
independence of the signature. Gene ontology (GO), Gene Set Variation Analysis
(GSVA) and Gene Set Enrichment Analysis (GSEA) were performed for functional
annotation of the differences. We found a three-gene signature, by applying
which, the anaplastic gliomas could be divided into low risk and high risk
groups. The two groups showed a high concordance with grade II and grade IV
gliomas, respectively. The high risk group was more aggressive and complex. The
three-gene signature showed diagnostic and prognostic value in anaplastic
gliomas.
PMID- 26436700
TI - Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies
vaccine for dogs.
AB - Developing efficacious oral rabies vaccines is an important step to increase
immunization coverage for stray dogs, which are not accessible for parenteral
vaccination. Our previous studies have demonstrated that recombinant rabies virus
(RABV) expressing cytokines/chemokines induces robust protective immune responses
after oral immunization in mice by recruiting and activating dendritic cells
(DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a
recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF
was constructed and used for oral vaccination in a dog model. Significantly more
DCs or B cells were activated in the peripheral blood of dogs vaccinated orally
with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE,
particularly at 3 days post immunization (dpi). As a result, significantly higher
levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized
with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were
protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01.
LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination
as detected by nested RT-PCR and immunohistochemistry. Taken together, our
results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine
candidate for dogs.
PMID- 26436701
TI - Length of paternal lifespan is manifested in the DNA methylome of their
nonagenarian progeny.
AB - The heritability of lifespan is 20-30%, but only a few genes associated with
longevity have been identified. To explain this discrepancy, the inheritance of
epigenetic features, such as DNA methylation, have been proposed to contribute to
the heritability of lifespan.We investigated whether parental lifespan is
associated with DNA methylation profile in nonagenarians. A regression model,
adjusted for differences in blood cell proportions, identified 659 CpG sites
where the level of methylation was associated with paternal lifespan. However, no
association was observed between maternal lifespan and DNA methylation. The 659
CpG sites associated with paternal lifespan were enriched outside of CpG islands
and were located in genes associated with development and morphogenesis, as well
as cell signaling. The largest difference in the level of methylation between the
progeny of the shortest-lived and longest-lived fathers was identified for CpG
sites mapping to CXXC5. In addition, the level of methylation in three Notch
genes (NOTCH1, NOTCH3 and NOTCH4) was also associated with paternal
lifespan.There are implications for the inheritance of acquired traits via
epigenetic mechanisms in mammals. Here we describe DNA methylation features that
are associated with paternal lifespan, and we speculate that the identified CpG
sites may represent intergenerational epigenetic inheritance.
PMID- 26436702
TI - Inheritance in MGUS and MM.
PMID- 26436704
TI - Mini-gut organoids: reconstitution of the stem cell niche.
AB - In the adult mammalian body, self-renewal of tissue stem cells is regulated by
extracellular niche environments in response to the demands of tissue
organization. Intestinal stem cells expressing Lgr5 constantly self-renew in
their specific niche at the crypt bottom to maintain rapid turnover of the
epithelium. Niche-regulated stem cell self-renewal is perturbed in several mouse
genetic models and during human tumorigenesis, suggesting roles for EGF, Wnt,
BMP/TGF-beta, and Notch signaling. In vitro niche reconstitution capitalizing on
this knowledge has enabled the growth of single intestinal stem cells into mini
gut epithelial organoids comprising Lgr5(+) stem cells and all types of
differentiated lineages. The mini-gut organoid culture platform is applicable to
various types of digestive tissue epithelium from multiple species. The mechanism
of self-renewal in organoids provides novel insights for organogenesis,
regenerative medicine, and tumorigenesis of the digestive system.
PMID- 26436705
TI - The hepatitis B virus receptor.
AB - Hepatitis B virus (HBV) infection affects 240 million people worldwide. A liver
specific bile acid transporter named the sodium taurocholate cotransporting
polypeptide (NTCP) has been identified as the cellular receptor for HBV and its
satellite, the hepatitis D virus (HDV). NTCP likely acts as a major determinant
for the liver tropism and species specificity of HBV and HDV at the entry level.
NTCP-mediated HBV entry interferes with bile acid transport in cell cultures and
has been linked with alterations in bile acid and cholesterol metabolism in vivo.
The human liver carcinoma cell line HepG2, complemented with NTCP, now provides a
valuable platform for studying the basic biology of the viruses and developing
treatments for HBV infection. This review summarizes critical findings regarding
NTCP's role as a viral receptor for HBV and HDV and discusses important questions
that remain unanswered.
PMID- 26436703
TI - Sculpting neural circuits by axon and dendrite pruning.
AB - The assembly of functional neural circuits requires the combined action of
progressive and regressive events. Regressive events encompass a variety of
inhibitory developmental processes, including axon and dendrite pruning, which
facilitate the removal of exuberant neuronal connections. Most axon pruning
involves the removal of axons that had already made synaptic connections; thus,
axon pruning is tightly associated with synapse elimination. In many instances,
these developmental processes are regulated by the interplay between neurons and
glial cells that act instructively during neural remodeling. Owing to the
importance of axon and dendritic pruning, these remodeling events require precise
spatial and temporal control, and this is achieved by a range of distinct
molecular mechanisms. Disruption of these mechanisms results in abnormal pruning,
which has been linked to brain dysfunction. Therefore, understanding the
mechanisms of axon and dendritic pruning will be instrumental in advancing our
knowledge of neural disease and mental disorders.
PMID- 26436707
TI - Modulation of host cell biology by plant pathogenic microbes.
AB - Plant-pathogen interactions can result in dramatic visual changes in the host,
such as galls, phyllody, pseudoflowers, and altered root-system architecture,
indicating that the invading microbe has perturbed normal plant growth and
development. These effects occur on a cellular level but range up to the organ
scale, and they commonly involve attenuation of hormone homeostasis and
deployment of effector proteins with varying activities to modify host cell
processes. This review focuses on the cellular-reprogramming mechanisms of
filamentous and bacterial plant pathogens that exhibit a biotrophic lifestyle for
part, if not all, of their lifecycle in association with the host. We also
highlight strategies for exploiting our growing knowledge of microbial host
reprogramming to study plant processes other than immunity and to explore
alternative strategies for durable plant resistance.
PMID- 26436708
TI - Milk and dairy consumption correlates with cerebral cortical as well as cerebral
white matter volume in healthy young adults.
AB - The objective of this study was to investigate the relation between habitual milk
and dairy consumption and brain morphology as assessed by magnetic resonance
imaging (MRI) investigations in 119 young healthy university students. MRI
measurements were performed on a Siemens Magnetom Trio Tim (3T) system while
FreeSurfer software suite was used for volumetric segmentation. Dietary habits
related to milk and dairy consumption were assessed by a structured
questionnaire. Total cerebral cortex, total cerebral white matter, and total
cerebral parenchyma were significantly related with cottage cheese and total
protein intake from milk and dairy also when controlled for age and gender in the
multivariate model. Our results indicate that dietary habits related with milk
and dairy are proportionally associated with volumes of both cerebral cortex and
cerebral white matter.
PMID- 26436709
TI - Choline Chloride Assisted Synthesis of N and Metal Codoped TiO2 and their
Photocatalytic Activity under Visible Light.
AB - A few nanocrystalline N,metal codoped TiO2 (metal = Cr, Mn, Fe, Co, Ni, Cu and
Zn) have been synthesized by a simple sol-gel method using choline chloride which
is biodegradable, low cost, nontoxic ionic salt both as a structure directing
agent and source of nitrogen. The prepared samples were well characterized by
XRD, HRTEM, FTIR, DRS, EDX, XPS and BET techniques. The photocatalytic activity
of all synthesized N, metal codoped TiO2 has been carried out for the degradation
of Reactive Black 5 dye under visible light irradiation and among them, N, Fe
codoped TiO2 was found to be the best for the degradation of Reactive Black 5
dye. The effect of incorporated metals on the photocatalytic activity of the
various modified TiO2 has been discussed in detail based on the mechanism
involved in the degradation of dye and their physico-chemical properties which
includes surface area, particle size, defect sites, phase, band gap and electron
hole recombination effect.
PMID- 26436710
TI - Ventral fronto-parietal contributions to the disruption of visual working memory
storage.
AB - The ability to maintain information in visual working memory (VWM) in the
presence of ongoing visual input allows for flexible goal-directed behavior.
Previous evidence suggests that categorical overlap between visual distractors
and the contents of VWM is associated with both the degree to which distractors
disrupt VWM performance and activation among fronto-parietal regions of cortex.
While within-category distractors have been shown to elicit a greater response in
ventral fronto-parietal regions, to date, no study has linked distractor-evoked
response of these regions to VWM performance costs. Here we examined the
contributions of ventral fronto-parietal cortex to the disruption of VWM storage
by manipulating memoranda-distractor similarity. Our results revealed that the
degree of activation across cortex was graded in a manner suggesting that
similarity between the contents of VWM and visual distractors influenced
distractor processing. While abrupt visual onsets failed to engage ventral fronto
parietal regions during VWM maintenance, objects sharing categorical- (Related
objects) and feature-overlap (Matched objects) with VWM elicited a significant
response in the right TPJ and right AI. Of central relevance, the magnitude of
activation in the right AI elicited by both types of distractor objects
subsequently predicted costs to binding change detection accuracy. In addition,
Related and Matched distractors differentially affected ventral-dorsal
connectivity between the right AI and dorsal parietal regions, uniquely
contributing to disruption of VWM storage. Together, our current results
implicate activation of ventral fronto-parietal cortex in disruption of VWM
storage, and disconnection between ventral frontal and dorsal parietal cortices
as a mechanism to protect the contents of VWM.
PMID- 26436711
TI - Modality-independent reduction mechanisms of primary sensory evoked fields in a
one-back task.
AB - Attentional modulation of early, primary sensory components is still a topic of
debate, as studies have produced conflicting results concerning the existence of
a modulation within the primary somatosensory cortex and its direction. We
previously showed that attention to tactile stimuli in a stream with visual
stimuli leads to a reduction of primary somatosensory components when
discrimination of different stimulus locations is requested. The question arises
whether this effect is universal and independent from the distracting or attended
modality. To test this, we compared the magnitude of primary somatosensory evoked
fields (somatosensory P50m) in a one-back task after tactile finger stimulation
during attention to tactile stimuli vs. auditory distraction in 28 volunteers. In
comparison to acoustic distraction, we found a significantly decreased primary
somatosensory activity when attending to tactile stimuli. Strikingly, similar
results were produced within the auditory modality: when attention was focused on
acoustic targets, primary auditory (auditory P50m) fields were lower as compared
to the situation when attention was directed to the tactile stimulation. Our
results clearly indicate that the type of task, independent from the modality, is
actually the crucial factor for the direction of modulation of early sensory
components by attention. Therefore, our finding of reduced primary sensory
components in a discrimination task represents a universal effect independent
from the distracting or attended modality.
PMID- 26436712
TI - Differential processing of melodic, rhythmic and simple tone deviations in
musicians--an MEG study.
AB - Rhythm and melody are two basic characteristics of music. Performing musicians
have to pay attention to both, and avoid errors in either aspect of their
performance. To investigate the neural processes involved in detecting melodic
and rhythmic errors from auditory input we tested musicians on both kinds of
deviations in a mismatch negativity (MMN) design. We found that MMN responses to
a rhythmic deviation occurred at shorter latencies than MMN responses to a
melodic deviation. Beamformer source analysis showed that the melodic deviation
activated superior temporal, inferior frontal and superior frontal areas whereas
the activation pattern of the rhythmic deviation focused more strongly on
inferior and superior parietal areas, in addition to superior temporal cortex.
Activation in the supplementary motor area occurred for both types of deviations.
We also recorded responses to similar pitch and tempo deviations in a simple, non
musical repetitive tone pattern. In this case, there was no latency difference
between the MMNs and cortical activation was smaller and mostly limited to
auditory cortex. The results suggest that prediction and error detection of
musical stimuli in trained musicians involve a broad cortical network and that
rhythmic and melodic errors are processed in partially different cortical
streams.
PMID- 26436713
TI - Facilitation and inhibition in attention: Functional dissociation of pre-stimulus
alpha activity, P1, and N1 components.
AB - Attention--the ability to attend to some things while ignoring others - can be
best described as an emergent property of many neural mechanisms, facilitatory
and inhibitory, working together to resolve competition for processing resources
and control of behavior. Previous EEG and MEG studies examining the neural
mechanisms underlying facilitation and inhibition of stimulus processing
typically used paradigms requiring alternating shifts of attention in the spatial
domain, with stimuli occurring at both attended and unattended locations. These
studies generally observed greater pre-stimulus alpha oscillations over task
irrelevant vs. relevant posterior regions and bilateral attentional modulations
of early sensory processing. In contrast, in the current series of experiments,
participants continuously attended to only one hemifield and stimuli were only
presented at the attended location, affording us an opportunity to elucidate the
inhibitory and facilitatory effects of attention in the brain in a context in
which spatial relevance was fixed. We found that continuous attention to one
hemifield did not modulate prestimulus alpha activity in ipsilateral regions but
did result in a perfectly lateralized P1 attention effect to ipsilateral
posterior regions. Moreover, we found a bilateral N1 effect. These findings
suggest that pre-stimulus alpha activity, the P1 and the N1 reflect qualitatively
different aspects of attention; While pre-stimulus alpha-band activity may
reflect a top-down inhibitory mechanism that critically depends on functional
competition between task-relevant and irrelevant sensory regions, the ipsilateral
P1 effect may reflect stimulus-triggered blocking of sensory processing in
irrelevant networks, and the N1 effect facilitation of task-relevant processing.
PMID- 26436706
TI - Mechanism and regulation of cytoplasmic dynein.
AB - Until recently, dynein was the least understood of the cytoskeletal motors.
However, a wealth of new structural, mechanistic, and cell biological data is
shedding light on how this complicated minus-end-directed, microtubule-based
motor works. Cytoplasmic dynein-1 performs a wide array of functions in most
eukaryotes, both in interphase, in which it transports organelles, proteins,
mRNAs, and viruses, and in mitosis and meiosis. Mutations in dynein or its
regulators are linked to neurodevelopmental and neurodegenerative diseases. Here,
we begin by providing a synthesis of recent data to describe the current model of
dynein's mechanochemical cycle. Next, we discuss regulators of dynein, with
particular focus on those that directly interact with the motor to modulate its
recruitment to microtubules, initiate cargo transport, or activate minus-end
directed motility.
PMID- 26436714
TI - Examining impacts of current-use pesticides in Southern Ontario using in situ
exposures of the amphipod Hyalella azteca.
AB - In situ exposures with Hyalella azteca were used to assess impacts of current-use
pesticides in Southern Ontario, Canada. Exposures were conducted over 2 growing
seasons within areas of high pesticide use: 1 site on Prudhomme Creek and 3 sites
on Twenty Mile Creek. Three sites on Spencer Creek, an area of low pesticide use,
were added in the second season. Surface water samples were collected every 2 wk
to 3 wk and analyzed for a suite of pesticides. Hyalella were exposed in situ for
1 wk every 4 wk to 6 wk, and survival and acetylcholinesterase (AChE) activity
were measured. Pesticides in surface waters reflected seasonal use patterns:
lower concentrations in spring and fall and higher concentrations during summer
months. Organophosphate insecticides (chlorpyrifos, azinphos methyl, diazinon)
and acid herbicides (2,4-dichlorophenoxyacetic acid [2,4-D], mecoprop) were
routinely detected in Prudhomme Creek, whereas neutral herbicides (atrazine,
metolachlor) dominated the pesticide signature of Twenty Mile Creek. Spencer
Creek contained fewer pesticides, which were measured at lower concentrations. In
situ effects also followed seasonal patterns: higher survival and AChE activity
in spring and fall, and lower survival and AChE activity during summer months.
The highest toxicity was observed at Prudhomme Creek and was primarily associated
with organophosphates. The present study demonstrated that current-use pesticides
in Southern Ontario were linked to in situ effects and identified sites of
concern requiring further investigation.
PMID- 26436715
TI - The [NiFe]-Hydrogenase of Pyrococcus furiosus Exhibits a New Type of Oxygen
Tolerance.
AB - We report the first direct electrochemical characterization of the impact of
oxygen on the hydrogen oxidation activity of an oxygen-tolerant, group 3, soluble
[NiFe]-hydrogenase: hydrogenase I from Pyrococcus furiosus (PfSHI), which grows
optimally near 100 degrees C. Chronoamperometric experiments were used to probe
the sensitivity of PfSHI hydrogen oxidation activity to both brief and prolonged
exposure to oxygen. For experiments between 15 and 80 degrees C, following short
(<200 s) exposure to 14 MUM O2 under oxidizing conditions, PfSHI always maintains
some fraction of its initial hydrogen oxidation activity; i.e., it is oxygen
tolerant. Reactivation experiments show that two inactive states are formed by
interaction with oxygen and both can be quickly (<150 s) reactivated. Analogous
experiments, in which the interval of oxygen exposure is extended to 900 s,
reveal that the response is highly temperature-dependent. At 25 degrees C, under
sustained 1% O2/ 99% H2 exposure, the H2oxidation activity drops nearly to zero.
However, at 80 degrees C, up to 32% of the enzyme's oxidation activity is
retained. Reactivation of PfSHI following sustained exposure to oxygen occurs on
a much longer time scale (tens of minutes), suggesting that a third inactive
species predominates under these conditions. These results stand in contrast to
the properties of oxygen-tolerant, group 1 [NiFe]-hydrogenases, which form a
single state upon reaction with oxygen, and we propose that this new type of
hydrogenase should be referred to as oxygen-resilient. Furthermore, PfSHI, like
other group 3 [NiFe]-hydrogenases, does not possess the proximal [4Fe3S] cluster
associated with the oxygen tolerance of some group 1 enzymes. Thus, a new
mechanism is necessary to explain the observed oxygen tolerance in soluble, group
3 [NiFe]-hydrogenases, and we present a model integrating both electrochemical
and spectroscopic results to define the relationships of these inactive states.
PMID- 26436716
TI - Vocational Psychology: Agency, Equity, and Well-Being.
AB - The present review organizes the vocational psychology literature published
between 2007 and 2014 into three overarching themes: Promoting (a) agency in
career development, (b) equity in the work force, and (c) well-being in work and
educational settings. Research on career adaptability, self-efficacy beliefs, and
work volition is reviewed in the agency section, with the goal of delineating
variables that promote or constrain the exercise of personal agency in academic
and occupational pursuits. The equity theme covers research on social class and
race/ethnicity in career development; entry and retention of women and people of
color in science, technology, engineering, and math (STEM) fields; and the career
service needs of survivors of domestic violence and of criminal offenders. The
goal was to explore how greater equity in the work force could be promoted for
these groups. In the well-being section, we review research on hedonic (work,
educational, and life satisfaction) and eudaimonic (career calling, meaning,
engagement, and commitment) variables, with the goal of understanding how well
being might be promoted at school and at work. Future research needs related to
each theme are also discussed.
PMID- 26436718
TI - WITHDRAWN: Psychosocial and pharmacological treatments for deliberate self harm.
PMID- 26436721
TI - The Folic Acid Rescue Strategy: High-Dose Folic Acid Supplementation in Early
Pregnancy.
PMID- 26436720
TI - Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic
asthma in the elderly.
AB - BACKGROUND: Asthma in the elderly (aged >= 65 years old) is a significant concern
with high morbidity, but the pathophysiology remains unclear particularly in late
onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE)
sensitization to be a risk factor for asthma in general populations; however, the
associations have not been examined in late-onset elderly asthma. OBJECTIVE: We
aimed to examine the associations of SE-IgE sensitization with late-onset asthma
in the elderly, using a database of elderly asthma cohort study. METHODS: A total
of 249 elderly patients with asthma and 98 controls were analysed. At baseline,
patients were assessed for demographics, atopy, induced sputum profiles and
comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE
levels were measured. Asthma severity was assessed on the basis of asthma
outcomes during a 12-month follow-up period. RESULTS: At baseline, serum SE-IgE
concentrations were significantly higher in patients with asthma than in controls
[median 0.16 (interquartile range 0.04-0.53) vs. 0.10 (0.01-0.19), P < 0.001].
Elderly asthma patients with high SE-IgE levels had specific characteristics of
having more severe asthma, sputum eosinophilia and CRS, compared to those with
lower SE-IgE levels. In multivariate logistic regression analyses, the
associations between serum SE-IgE concentrations and severe asthma were
significant, independently of covariables [SE-IgE-high (>= 0.35 kU/L) vs.
negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86
30.03, P = 0.005]. Multiple correspondence analyses also showed that high serum
SE-IgE level had close relationships with severe asthma, CRS and sputum
eosinophilia together. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first
report on the significant associations of SE-IgE sensitization with late-onset
asthma in the elderly, particularly severe eosinophilic asthma with CRS
comorbidity. Our findings indicate a potential implication of SE in the high
morbidity burden of elderly asthma and suggest clues to the pathogenesis of
severe late-onset eosinophilic asthma in the elderly.
PMID- 26436717
TI - The Affective Neuroscience of Aging.
AB - Although aging is associated with clear declines in physical and cognitive
processes, emotional functioning fares relatively well. Consistent with this
behavioral profile, two core emotional brain regions, the amygdala and
ventromedial prefrontal cortex, show little structural and functional decline in
aging, compared with other regions. However, emotional processes depend on
interacting systems of neurotransmitters and brain regions that go beyond these
structures. This review examines how age-related brain changes influence
processes such as attending to and remembering emotional stimuli, regulating
emotion, and recognizing emotional expressions, as well as empathy, risk taking,
impulsivity, behavior change, and attentional focus.
PMID- 26436723
TI - Understanding the gender gap: Social cognitive changes during an introductory
stem course.
AB - Despite robust support for the basic theoretical model of social cognitive career
theory (Lent, Brown, & Hackett, 1994) and predictions that, for example,
increases (or declines) in self-efficacy would lead to subsequent increases (or
declines) in interest, there has been surprisingly little longitudinal research
that has directly examined the extent to which members of different groups (e.g.,
women and men) actually do experience changes in critical social-cognitive
variables over time early in their curricula in the fields of science,
technology, engineering, and mathematics (STEM). Knowing the extent to which such
changes occur in typical introductory undergraduate courses is important for
targeting interventions to increase persistence of underrepresented groups in
STEM. We measured social-cognitive-career-theory-relevant variables near the
middle and at the end of the 1st semester of a gateway introductory chemistry
course and found that women had lower STEM self-efficacy, coping self-efficacy,
and STEM interest than did men, even after controlling for actual course
performance. Although there were no detrimental changes across the semester for
women or men, men experienced a small but significant increase in their perceived
support for pursuing a STEM degree, whereas women did not.
PMID- 26436722
TI - Toll-IL1 receptor-mediated innate immune responses vary across HBV genotype and
predict treatment response to pegylated-IFN in HBeAg-positive CHB patients.
AB - Patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB)
have suppressed TLR2 expression, function and cytokine production. The aim of
this study was to explore the importance of hepatitis B virus (HBV) genotype in
innate immune responses and investigate whether Toll-like receptor (TLR)
expression/function has potential roles as predictive biomarkers of successful
therapy with pegylated interferon (Peg-IFN) therapy of HBeAg seroconversion in
HBeAg-positive patients. We showed that as early as 4 weeks after initiation of
Peg-IFN, future HBeAg seroconverters had significantly elevated levels of TLR2
expression on monocytes. TLR2-associated IL-6 production at baseline and week 4
of therapy and TLR4 IL-6 production at week 4 were also markedly elevated in
HBeAg seroconverters. HBV genotype also influenced treatment response, with
genotypes A and B more likely to seroconvert than D. We were able to demonstrate
that these differences were due in part to the interaction of the specific HBeAg
proteins with TLR pathway adaptor molecules, and these interactions were genotype
dependent. HBeAg-mediated modulation of TLR signalling was also observed in Huh7
cells, following stimulation with Pam3Cys. Importantly, the addition of IFN-alpha
to TLR2-stimulated cells cotransfected with an HBeAg expression plasmid reversed
HBeAg-mediated suppression of hepatocytes. These findings demonstrate that
patients with an activated inflammatory response are much more likely to respond
to IFN therapy, with TLR responses showing promise as potential biomarkers of
HBeAg seroconversion in this setting. Furthermore, our findings suggest there is
differential genotype-specific HBeAg suppression of innate signalling pathways
which may account for some of the clinical differences observed across the CHB
spectrum.
PMID- 26436724
TI - A dyadic study of multicultural counseling competence.
AB - Using the Kenny, Kashy, and Cook (2006) one-with-many method, we investigated
client and counselor reports of counselors' level of multicultural counseling
competence (MCC) across 4 therapy sessions at a university counseling center.
Specifically, we analyzed the association between counselor MCC and client
psychological well-being among 133 clients of color receiving psychotherapy from
24 counselors. We found that both client and counselor perspectives suggested
that some counselors possessed generally higher MCC than others. Counselors' self
assessments of MCC, however, did not relate with their clients' assessments of
counselor MCC-replicating findings from past studies of MCC. On average,
counselors whose clients generally perceived them as more multiculturally
competent did not report improved psychological well-being at the fourth session.
Likewise, counselors who generally reported more MCC did not have clients who
improved more in psychological well-being than would be expected over 4 sessions.
Notably, at the dyad-level, clients who rated their counselor more highly on MCC
than their counselors' other clients tended to report greater improvement in well
being. Suggestions for future MCC research involving dyadic analytic designs are
described. (PsycINFO Database Record
PMID- 26436725
TI - Characterization of Intrinsic Properties of Promoters.
AB - Accurate characterization of promoter behavior is essential for the rational
design of functional synthetic transcription networks such as logic gates and
oscillators. However, transcription rates observed from promoters can vary
significantly depending on the growth rate of host cells and the experimental and
genetic contexts of the measurement. Furthermore, in vivo measurement methods
must accommodate variation in translation, protein folding, and maturation rates
of reporter proteins, as well as metabolic load. The external factors affecting
transcription activity may be considered to be extrinsic, and the goal of
characterization should be to obtain quantitative measures of the intrinsic
characteristics of promoters. We have developed a promoter characterization
method that is based on a mathematical model for cell growth and reporter gene
expression and exploits multiple in vivo measurements to compensate for variation
due to extrinsic factors. First, we used optical density and fluorescent reporter
gene measurements to account for the effect of differing cell growth rates.
Second, we compared the output of reporter genes to that of a control promoter
using concurrent dual-channel fluorescence measurements. This allowed us to
derive a quantitative promoter characteristic (rho) that provides a robust
measure of the intrinsic properties of a promoter, relative to the control. We
imposed different extrinsic factors on growing cells, altering carbon source and
adding bacteriostatic agents, and demonstrated that the use of rho values reduced
the fraction of variance due to extrinsic factors from 78% to less than 4%. This
is a simple and reliable method to quantitatively describe promoter properties.
PMID- 26436726
TI - Polysomnographic findings after adenotonsillectomy for obstructive sleep apnoea
in obese and non-obese children: a systematic review and meta-analysis.
AB - BACKGROUND: Use of polysomnography (PSG) is the gold standard of diagnosis and
measurement of treatment effectiveness for paediatric obstructive sleep apnoea
(OSA). Although adenotonsillectomy (T&A) is effective in diminishing the apnoea
hypopnoea index (AHI), a meta-analysis of postoperative changes for all other PSG
parameters and outcome comparisons between obese and non-obese children following
T&A have never been conducted. OBJECTIVE OF REVIEW: To comprehensively review
polysomnographic findings after surgery for obese and non-obese children with
OSA. SEARCH STRATEGY: Study protocol was registered on PROSPERO (CRD42013004737).
Two authors independently searched databases including PubMed, MEDLINE, EMBASE
and Cochrane Review from January 1997 to July 2014. The keywords used included
the following: sleep apnea, OSA, sleep apnea syndromes, tonsillectomy,
adenoidectomy, infant, child, adolescent, and Humans. EVALUATION METHOD: A
comprehensive systematic review and meta-analysis for literature for OSA children
treated by T&A with polysomnography data. Random-effects model was applied to
determine postoperative sleep parameter changes and the surgical success rate
between obese and non-obese groups. The quality of studies was assessed using the
Newcastle-Ottawa Scale. RESULTS: In total, 51 studies with 3413 subjects were
enrolled. After surgery, sleep architecture was altered by a significant decrease
in sleep stage 1, and an increase in slow-wave sleep and the rapid eye movement
stage, and enhanced sleep efficiency. The mean difference between pre- and
postoperative was a significant reduction of 12.4 event/h in AHI, along with a
reduction of obstructive index, hypopnoea index, central index and arousal index.
Mean and minimum oxygen saturation increased significantly after surgery. The
overall success rate was 51% for postoperative AHI <1 (obese versus non-obese
versus combined, 34% versus 49% versus 56%), and 81% for AHI <5 (obese versus non
obese versus combined, 61% versus 87% versus 84%). Meta-regression analyses
demonstrate that postoperative AHI was positively correlated with AHI and body
mass index z score before surgery. CONCLUSIONS: Meta-analysis of current
literature shows T&A offers prominent improvement in a variety of sleep
parameters. Improvements in non-obese children exceeded those for obese children.
Postoperative residual OSA remained in roughly half of the children, especially
those with severe disease and obesity, making additional treatment strategies
and/or long-term follow-up highly desirable.
PMID- 26436727
TI - Retroactive application of the new kidney allocation system to renal transplants
performed in the ECD/SCD era.
AB - The kidney allocation system (KAS) aims to improve deceased donor kidney
transplant outcomes by matching of donor allografts and kidney recipients using
the kidney donor risk index (KDRI) and recipient estimated post-transplant
survival (EPTS) indices. In this single-center study, KAS was retroactively
applied to 573 adult deceased donor kidney transplants (2004-2012) performed in
the extended criteria/standard criteria donor (ECD/SCD) era. Donor KDRI and
recipient EPTS were calculated, and transplants were analyzed to identify KAS
fits. These were defined as allocation of top 20% allografts to top 20%
recipients and bottom 80% allografts to bottom 80% recipients. On retroactive
calculation, 70.2% of all transplants fit the KAS. Transplants that fit the KAS
had inferior 1- and 5-yr patient survival (95.5% vs. 98.8%, p = 0.048, and 83.4%
vs. 91.7%, p = 0.018) and similar 1- and 5-yr graft survival compared to
transplants that did not fit the KAS (91.3% vs. 94.1%, p = 0.276, and 72.7% vs.
73.9%, p = 0.561). While EPTS correlated with recipient survival (HR = 2.96, p <
0.001), KDRI correlated with both recipient (HR = 3.56, p < 0.001) and graft
survival (HR = 3.23, p < 0.001). Overall, retroactive application of the KAS to
transplants performed in the ECD/SCD era did not identify superior patient
survival for kidneys allocated in accordance with the KAS.
PMID- 26436728
TI - Common Polymorphisms within Genes Encoding Platelet Receptors: Still a Way to Go.
PMID- 26436729
TI - Experimental Research Examining How People Can Cope with Uncertainty Through Soft
Haptic Sensations.
AB - Human beings are constantly surrounded by uncertainty and change. The question
arises how people cope with such uncertainty. To date, most research has focused
on the cognitive strategies people adopt to deal with uncertainty. However,
especially when uncertainty is due to unpredictable societal events (e.g.,
economical crises, political revolutions, terrorism threats) of which one is
unable to judge the impact on one's future live, cognitive strategies (like
seeking additional information) is likely to fail to combat uncertainty. Instead,
the current paper discusses a method demonstrating that people might deal with
uncertainty experientially through soft haptic sensations. More specifically,
because touching something soft creates a feeling of comfort and security, people
prefer objects with softer as compared to harder properties when feeling
uncertain. Seeking for softness is a highly efficient and effective tool to deal
with uncertainty as our hands are available at all times. This protocol describes
a set of methods demonstrating 1) how environmental (un)certainty can be
situationally activated with an experiential priming procedure, 2) that the
quality of the softness experience (what type of softness and how it is
experienced) matters and 3) how uncertainty can be reduced using different
methods.
PMID- 26436730
TI - Remanagement of Singlet and Triplet Excitons in Single-Emissive-Layer Hybrid
White Organic Light-Emitting Devices Using Thermally Activated Delayed
Fluorescent Blue Exciplex.
AB - A high-performance hybrid white organic light-emitting device (WOLED) is
demonstrated based on an efficient novel thermally activated delayed fluorescence
(TADF) blue exciplex system. This device shows a low turn-on voltage of 2.5 V and
maximum forward-viewing external quantum efficiency of 25.5%, which opens a new
avenue for achieving high-performance hybrid WOLEDs with simple structures.
PMID- 26436732
TI - Speciation Progress: A Case Study on the Bushcricket Poecilimon veluchianus.
AB - Different mechanisms such as selection or genetic drift permitted e.g. by
geographical isolation can lead to differentiation of populations and could cause
subsequent speciation. The two subspecies of Poecilimon veluchianus, a
bushcricket endemic to central Greece, show a parapatric distribution and are
partially reproductively isolated. Therefore, P. veluchianus is suitable to
investigate an ongoing speciation process. We based our analysis on sequences of
the internal transcribed spacer (ITS) and the mitochondrial control region (CR).
The population genetic analysis based on the nuclear marker ITS revealed a
barrier to gene flow within the range of Poecilimon veluchianus, which
corresponds well to the described subspecies. In contrast to the results based on
the nuclear ITS marker, the mitochondrial CR marker does not clearly support the
separation into two subspecies with restricted gene flow and a clear contact
zone. Furthermore, we could identify isolation by distance (IBD) as one important
mechanism responsible for the observed genetic structure (based on the ITS
marker). The population genetic analysis based on the nuclear marker ITS also
suggests the existence of hybrids in the wild. Furthermore, the simultaneous lack
of strong prezygotic barriers and the presence of postzygotic mating barriers,
observed in previous laboratory experiments, suggest that a secondary contact
after an allopatric phase is more likely than parapatric speciation.
PMID- 26436731
TI - Cortical Composition Hierarchy Driven by Spine Proportion Economical Maximization
or Wire Volume Minimization.
AB - The structure and quantitative composition of the cerebral cortex are
interrelated with its computational capacity. Empirical data analyzed here
indicate a certain hierarchy in local cortical composition. Specifically, neural
wire, i.e., axons and dendrites take each about 1/3 of cortical space, spines and
glia/astrocytes occupy each about (1/3)(2), and capillaries around (1/3)(4).
Moreover, data analysis across species reveals that these fractions are roughly
brain size independent, which suggests that they could be in some sense optimal
and thus important for brain function. Is there any principle that sets them in
this invariant way? This study first builds a model of local circuit in which
neural wire, spines, astrocytes, and capillaries are mutually coupled elements
and are treated within a single mathematical framework. Next, various forms of
wire minimization rule (wire length, surface area, volume, or conduction delays)
are analyzed, of which, only minimization of wire volume provides realistic
results that are very close to the empirical cortical fractions. As an
alternative, a new principle called "spine economy maximization" is proposed and
investigated, which is associated with maximization of spine proportion in the
cortex per spine size that yields equally good but more robust results.
Additionally, a combination of wire cost and spine economy notions is considered
as a meta-principle, and it is found that this proposition gives only marginally
better results than either pure wire volume minimization or pure spine economy
maximization, but only if spine economy component dominates. However, such a
combined meta-principle yields much better results than the constraints related
solely to minimization of wire length, wire surface area, and conduction delays.
Interestingly, the type of spine size distribution also plays a role, and better
agreement with the data is achieved for distributions with long tails. In sum,
these results suggest that for the efficiency of local circuits wire volume may
be more primary variable than wire length or temporal delays, and moreover, the
new spine economy principle may be important for brain evolutionary design in a
broader context.
PMID- 26436733
TI - Systematic review of effects of current transtibial prosthetic socket designs-
Part 2: Quantitative outcomes.
AB - This review is an attempt to untangle the complexity of transtibial prosthetic
socket fit and perhaps find some indication of whether a particular prosthetic
socket type might be best for a given situation. In addition, we identified
knowledge gaps, thus providing direction for possible future research. We
followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta
Analyses) guidelines, using medical subject headings and standard key words to
search for articles in relevant databases. No restrictions were made on study
design and type of outcome measure used. From the obtained search results (n =
1,863), 35 articles were included. The relevant data were entered into a
predefined data form that included the Downs and Black risk of bias assessment
checklist. This article presents the results from the systematic review of the
quantitative outcomes (n = 27 articles). Trends indicate that vacuum-assisted
suction sockets improve gait symmetry, volume control, and residual limb health
more than other socket designs. Hydrostatic sockets seem to create less
inconsistent socket fittings, reducing a problem that greatly influences outcome
measures. Knowledge gaps exist in the understanding of clinically meaningful
changes in socket fit and its effect on biomechanical outcomes. Further, safe and
comfortable pressure thresholds under various conditions should be determined
through a systematic approach.
PMID- 26436734
TI - Temporal Monitoring of Differentiated Human Airway Epithelial Cells Using
Microfluidics.
AB - The airway epithelium is exposed to a variety of harmful agents during breathing
and appropriate cellular responses are essential to maintain tissue homeostasis.
Recent evidence has highlighted the contribution of epithelial barrier
dysfunction in the development of many chronic respiratory diseases. Despite
intense research efforts, the responses of the airway barrier to environmental
agents are not fully understood, mainly due to lack of suitable in vitro models
that recapitulate the complex in vivo situation accurately. Using an
interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the
airway epithelium, incorporating fully differentiated primary human airway
epithelial cells at the air-liquid interface and a basolateral microfluidic
supply of nutrients simulating the interstitial flow observed in vivo. Through
combination of the microfluidic culture system with an automated fraction
collector the kinetics of cellular responses by the airway epithelium to
environmental agents can be analysed at the early phases for the first time and
with much higher sensitivity compared to common static in vitro models. Following
exposure of primary differentiated epithelial cells to pollen we show that
CXCL8/IL-8 release is detectable within the first 2h and peaks at 4-6h under
microfluidic conditions, a response which was not observed in conventional static
culture conditions. Such a microfluidic culture model is likely to have utility
for high resolution temporal profiling of toxicological and pharmacological
responses of the airway epithelial barrier, as well as for studies of disease
mechanisms.
PMID- 26436738
TI - The Link Between Sauna Bathing and Mortality May Be Noncausal.
PMID- 26436739
TI - The Link Between Sauna Bathing and Mortality May Be Noncausal.
PMID- 26436740
TI - The Link Between Sauna Bathing and Mortality May Be Noncausal-Reply.
PMID- 26436741
TI - Study Design for Vitamin D Randomized Clinical Trials.
PMID- 26436742
TI - Study Design for Vitamin D Randomized Clinical Trials-Reply.
PMID- 26436743
TI - Another Report of Familial Spontaneous Coronary Artery Dissection.
PMID- 26436744
TI - Another Report of Familial Spontaneous Coronary Artery Dissection-Reply.
PMID- 26436745
TI - Physical Function and Hospital Readmissions.
PMID- 26436746
TI - Vitamin D Supplements and the Risk of Falls.
PMID- 26436747
TI - Physical Function and Hospital Readmissions-Reply.
PMID- 26436748
TI - Selecting the Optimal Design for Drug Discontinuation Trials in a Setting of
Advanced, Life-Limiting Illness.
PMID- 26436749
TI - Vitamin D Supplements and the Risk of Falls-Reply.
PMID- 26436750
TI - Selecting the Optimal Design for Drug Discontinuation Trials in a Setting of
Advanced, Life-Limiting Illness.
PMID- 26436751
TI - Selecting the Optimal Design for Drug Discontinuation Trials in a Setting of
Advanced, Life-Limiting Illness-Reply.
PMID- 26436752
TI - Diet and Colorectal Cancer Incidence.
PMID- 26436753
TI - Noninvasive Testing in Patients With Chest Pain.
PMID- 26436754
TI - Diet and Colorectal Cancer Incidence-Reply.
PMID- 26436756
TI - Error in Figure.
PMID- 26436755
TI - Noninvasive Testing in Patients With Chest Pain-Reply.
PMID- 26436757
TI - Microwave, r0 Structural Parameters, Conformational Stability, and Vibrational
Assignment of (Chloromethyl)fluorosilane.
AB - The FT-microwave spectrum (6.5-26 GHz) of (chloromethyl)fluorosilane (ClCH2
SiH2F) has been recorded and 250 transitions for the parent species along with
(13)C, (37)Cl, (29)Si, and (30)Si isotopologues have been assigned for trans
conformer. Infrared spectra (3100 to 400 cm(-1)) of gas, solid, and the variable
temperature (-100 to -60 degrees C) studies of the infrared spectra of the
sample dissolved in xenon have been recorded. Additionally, the variable
temperature (-153 to -133 degrees C) studies of the Raman spectra of the sample
dissolved in krypton have been recorded. The enthalpy difference between the
trans and gauche conformers in xenon solutions has been determined to be 109 +/-
15 cm(-1) (1.47 +/- 0.16 kJ mol(-1)), and in krypton solution, the enthalpy
difference has been determined to be 97 +/- 16 cm(-1) (1.16 +/- 0.19 kJ mol(-1))
with the trans conformer as the more stable form. Approximately 46 +/- 2% of the
trans form is present at ambient temperature. By utilizing the microwave
rotational constants of five isotopologues for trans and the structural
parameters predicted from MP2(full)/6-311+G(d,p) calculations, adjusted r0
parameters have been obtained for trans conformer. The r0 structural parameter
values for the trans form are for the heavy atom distances (A): Si-F = 1.608 (3);
C-Cl = 1.771 (3); Si-C = 1.884 (3); and angles (deg): ?FSiC = 108.9 (5); ?ClCSi =
104.9 (5). The results are discussed and compared to some related molecules.
PMID- 26436759
TI - A Patient-Centered Understanding of the Referral System in Ethiopian Primary
Health Care Units.
AB - BACKGROUND: Primary healthcare systems in sub-Saharan Africa have undergone
substantial development in an effort to expand access to appropriate facilities
through a well-functioning referral system. The objective of this study was to
evaluate the current patterns of seeking prior care before arriving at a health
center or a hospital as a key aspect of the referral system of the primary health
care unit (PHCU) in three regions in Ethiopia. We examined what percentage of
patients had either sought prior care or had been referred to the present
facility and identified demographic and clinical factors associated with having
sought prior care or having been referred. METHODS AND FINDINGS: We conducted a
cross-sectional study using face-to-face interviews in the local language with
796 people (99% response rate) seeking outpatient care in three primary health
care units serving approximately 100,000 people each and reflecting regional and
ethnic diversity; 53% (N = 418) of the sample was seeking care at hospital
outpatient departments, and 47% of the sample was seeking care at health centers
(N = 378). We used unadjusted and adjusted logistic regression to identify
factors associated with having been referred or sought prior care. Our findings
indicated that only 10% of all patients interviewed had been referred to their
current place of care. Among those in the hospital population, 14% had been
referred; among those in the health center population, only 6% had been referred.
Of those who had been referred to the hospital, most (74%) had been referred by a
health center. Among those who were referred to the health center, the plurality
portion (32%) came from a nearby hospital (most commonly for continued HIV
treatment or early childhood vaccinations); only 18% had come from a health post.
Among patients who had not been formally referred, an additional 25% in the
hospital sample and 10% in the health center sample had accessed some prior
source of care for their present health concern. In the adjusted analysis, living
a longer distance from the source of care and needing more specialized care were
correlated with having sought prior care in the hospital sample. We found no
factors significantly associated with having sought prior care in the health
center sample. CONCLUSIONS: The referral system among health facilities in
Ethiopia is used by a minority of patients, suggesting that intended connections
between health posts, health centers, and hospitals may need strengthening to
increase the efficiency of primary care nationally.
PMID- 26436758
TI - Thinking Forward: Future-oriented Thinking among Patients with Tobacco-associated
Thoracic Diseases and Their Surrogates.
AB - RATIONALE: The goal of shared decision making is to match patient preferences,
including evaluation of potential future outcomes, with available management
options. Yet, it is unknown how patients with smoking-related thoracic diseases
or their surrogates display future-oriented thinking. OBJECTIVES: To document
prevalent themes in patients' and potential surrogate decision makers' future
oriented thinking when facing preference-sensitive choices. METHODS: We conducted
44 scenario-based semistructured interviews among a diverse group of outpatients
with smoking-associated thoracic diseases and potential surrogates for whom one
of three preference-sensitive decisions would be medically relevant. Using
content analysis, we documented prevalent themes to understand how these
individuals display future-oriented thinking. MEASUREMENTS AND MAIN RESULTS:
Patients and potential surrogates generally expressed expectations for future
outcomes but also acknowledged their limitations in doing so. When thinking about
potential outcomes, decision makers relied on past experiences, including those
only loosely related; perceived familiarity with treatment options; and
spirituality. The content of these expectations included effects on family,
emotional predictions, and prognostication. For surrogates, a tension existed
between hope-based and fact-based expectations. CONCLUSIONS: Patients and
surrogates may struggle to generate expectations, and these future-oriented
thoughts may be based on loosely related past experiences or unrealistic
optimism. These tendencies may lead to errors, preventing selection of treatments
that promote true preferences. Clinicians should explore how decision makers
engage in future-oriented thinking and what their expectations are as a component
of the shared decision-making process. Future research should evaluate whether
targeted guidance in future-oriented thinking may improve outcomes important to
patients.
PMID- 26436761
TI - Genetic and Epigenetic Mechanisms Linking Pain and Psychiatric Disorders.
AB - The neurophysiological link between neuropathic pain and depression remains
unknown despite evident high comorbidity of these two disorders. However, there
is convincing evidence that genotype plays a role in both pain and depression.
Using various types of genetic analysis - population genetics, cytogenetics and
molecular technologies - specific genes have been implicated in mediating almost
all aspects of nociception and mood disorders. The current review attempts to
identify specific genes and epigenetic mechanisms common to both disorders. It is
concluded that external and internal factors (inflammation, stress, gender, etc.)
that contribute to the pathologies may do so through epigenetic mechanisms that
may affect expression of these particular genes. The possible involvement of
epigenetic regulation in pain and psychiatric disorders suggests that treatments
targeting epigenetic mechanisms that mediate adverse life events should be
considered.
PMID- 26436762
TI - Conductance of graphene flakes contacted at their corners.
AB - Linear conductance of junctions formed by graphene flakes with the order of the
nanometer-thick electrodes attached at the corners of the flakes is studied. The
explored structures have sizes up to 20,000 atoms and the conductance is studied
as a function of applied gate voltage varied around the Fermi level. The finding,
obtained computationally, is that junctions formed by armchair-edge flakes with
the electrodes connected at the acute-angle corners block the electron transport
while only junctions with such electrodes at the obtuse-angle corners tend to
provide the high electrical conductance typical for metallic GNRs. The finding in
the case of zig-zag edges is similar with the exception of a relatively narrow
gate voltage interval in which each studied junction is highly conductive as
mediated by the edge states. The contrast between the conductive and insulating
setups is typically several orders of magnitude in terms of ratio of their
conductances. The main results of the paper also remain to a large extent valid
in the presence of edge disorder.
PMID- 26436760
TI - GPR55 promotes migration and adhesion of colon cancer cells indicating a role in
metastasis.
AB - BACKGROUND AND PURPOSE: Tumour cell migration and adhesion constitute essential
features of metastasis. G-protein coupled receptor 55 (GPR55), a lysophospholipid
receptor, has been shown to play an important role in carcinogenesis. Here, we
investigated the involvement of GPR55 in migration and metastasis of colon cancer
cells. EXPERIMENTAL APPROACH: Adhesion and migration assays using the highly
metastatic colon cancer cell line HCT116 and an in vivo assay of liver metastasis
were performed. The GPR55 antagonist CID16020046, cannabidiol, a putative GPR55
antagonist and GPR55 siRNA were used to block GPR55 activity in HCT116 colon
cancer cells. KEY RESULTS: HCT116 cells showed a significant decrease in adhesion
to endothelial cells and in migration after blockade with CID16020046 or
cannabidiol. The inhibitory effects of CID16020046 or cannabidiol were averted by
GPR55 siRNA knock down in cancer cells. The integrity of endothelial cell
monolayers was increased after pretreatment of HCT116 cells with the antagonists
or after GPR55 siRNA knockdown while pretreatment with lysophosphatidylinositol
(LPI), the endogenous ligand of GPR55, decreased integrity of the monolayers. LPI
also induced migration in GPR55 overexpressing HCT116 cells that was blocked by
GPR55 antagonists. In a mouse model of metastasis, the arrest of HCT116 cancer
cells in the liver was reduced after treatment with CID16020046 or cannabidiol.
Increased levels of LPI (18:0) were found in colon cancer patients when compared
with healthy individuals. CONCLUSIONS AND IMPLICATIONS: GPR55 is involved in the
migratory behaviour of colon carcinoma cells and may serve as a pharmacological
target for the prevention of metastasis. (c) 2015 The British Pharmacological
Society.
PMID- 26436764
TI - Will modern immunotherapies become the standard of care for advanced synchronous
or metachronous cancers?
PMID- 26436763
TI - Spatial clusters of child lower respiratory illnesses associated with community
level risk factors.
AB - Identifying geographic areas with increased incidence of disease may elucidate
community-level risk factors for intervention development. Lower respiratory
illnesses (LRIs) are the leading cause of death in children and are associated
with other morbidities. We assessed geographic clustering of LRIs and evaluated
if these spatial patterns and associated risk factors differed by phenotype.
Participants enrolled at birth in the Tucson Children's Respiratory Study were
followed through age three for physician diagnosed LRIs. Spatial clustering
analysis, based upon each participant's birth address, was performed for four LRI
phenotypes. We conducted principal component analysis at the census tract level
to generate indices for lower socioeconomic status (SES), poorer housing
conditions, and increased air pollution. Enrollment addresses were mapped for 812
subjects, of whom 58.4%, 33.5%, 34.2%, and 23.4% had any LRI, a wheezing LRI, a
viral LRI, and a respiratory syncytial virus (RSV) LRI, respectively. Patterns of
spatial clustering and associated risk factors differed by LRI phenotype.
Multivariable regression analyses showed that wheezing LRI clusters were
associated with increased air pollution (OR = 1.18, P = 0.01). Being in a viral
cluster was associated with poorer housing conditions (OR = 1.28, P = 0.01),
while being in a RSV cluster was associated with increased air pollution (OR =
1.14, P = 0.006), poorer housing conditions (OR = 1.54, P = 0.003), and higher
SES (OR = 0.77, P = 0.001). Our use of social and environmental indices allowed
us to identify broad contextual factors that may contribute to increased
incidence of LRIs in specific geographic regions. To reduce LRI incidence,
multifaceted interventions should be developed at the community level. Pediatr
Pulmonol. 2016;51:633-642. (c) 2015 Wiley Periodicals, Inc.
PMID- 26436765
TI - Age-related motor dysfunction: Manual slowing in Gorilla gorilla gorilla.
AB - Aging in humans and rhesus monkeys is commonly associated with motor function
decrements including dexterity, speed, and strength. Despite their longevity and
phylogenetic relatedness to humans, the effects of aging on motor function in non
human apes have been minimally studied. We conducted two experiments with western
lowland gorillas (11-54 years of age) to determine whether aged gorillas exhibit
motor deficits similar to those seen in other species. In experiment one,
gorillas extracted up to 12 food rewards lodged in holes of a Lexan board.
Extraction rates were calculated for eight test sessions. A repeated measures
ANOVA revealed no main effects of session or sex on extraction rate, but a
significant main effect of age. Comparisons between the first and last sessions
showed that experience significantly improved extraction rates in young but not
aged gorillas. In experiment two, gorillas retrieved a hex nut from three
differently shaped rods with each hand for a reward. Latencies of retrieval were
calculated for 16 test sessions. A repeated measures ANOVA revealed significant
main effects of age class, sex, and session. There were significant interactions
between session and sex, session and age, and session, sex, and age. These
findings held when analyzing each rod shape separately. Post hoc comparisons
revealed that young gorillas were significantly faster at the task than aged
gorillas, and females were faster than males. This finding held only for the
question mark shaped rod when analyzing each rod shape separately. Comparisons
between the first and last sessions showed that experience did not significantly
improve latencies in either age or sex class. The direction of these results are
congruent with previous findings in humans and monkeys and suggest that aged
gorillas experience deficits in bimanual coordination compared to younger
gorillas and that age and sex influence fine motor ability in gorillas.
PMID- 26436766
TI - Myeloid Cell Arg1 Inhibits Control of Arthritogenic Alphavirus Infection by
Suppressing Antiviral T Cells.
AB - Arthritogenic alphaviruses, including Ross River virus (RRV) and chikungunya
virus (CHIKV), are responsible for explosive epidemics involving millions of
cases. These mosquito-transmitted viruses cause inflammation and injury in
skeletal muscle and joint tissues that results in debilitating pain. We
previously showed that arginase 1 (Arg1) was highly expressed in myeloid cells in
the infected and inflamed musculoskeletal tissues of RRV- and CHIKV-infected
mice, and specific deletion of Arg1 from myeloid cells resulted in enhanced viral
control. Here, we show that Arg1, along with other genes associated with
suppressive myeloid cells, is induced in PBMCs isolated from CHIKV-infected
patients during the acute phase as well as the chronic phase, and that high Arg1
expression levels were associated with high viral loads and disease severity.
Depletion of both CD4 and CD8 T cells from RRV-infected Arg1-deficient mice
restored viral loads to levels detected in T cell-depleted wild-type mice.
Moreover, Arg1-expressing myeloid cells inhibited virus-specific T cells in the
inflamed and infected musculoskeletal tissues, but not lymphoid tissues,
following RRV infection in mice, including suppression of interferon-gamma and
CD69 expression. Collectively, these data enhance our understanding of the immune
response following arthritogenic alphavirus infection and suggest that
immunosuppressive myeloid cells may contribute to the duration or severity of
these debilitating infections.
PMID- 26436768
TI - Nasopalpebral Schwannomas and Human Immunodeficiency Virus Infection.
AB - OBJECTIVE: To report a case of a schwannoma of nasopalpebral location, occurring
in a human immunodeficiency virus (HIV)-positive patient. CLINICAL PRESENTATION
AND INTERVENTION: A 55-year-old man presented with a nasopalpebral painless
tumefaction, pneumopathy and HIV-related immunodepression after stopping
combination antiretroviral therapy. Magnetic resonance imaging showed
subcutaneous masses, with contrast enhancement of the left nose pyramid, internal
cantus and inferior palpebral area, suspicious of Kaposi sarcoma. The resected
specimen showed schwannoma histology, with tumor cells expressing S100 protein
and WT1. CONCLUSION: The features of a rare case of facial schwannoma of
nasopalpebral location in an HIV-positive patient are reported. The diagnosis may
be difficult before microscopic examination, with imaging features suggesting a
Kaposi sarcoma.
PMID- 26436769
TI - Three-Dimensional Heterostructures of MoS2 Nanosheets on Conducting MoO2 as an
Efficient Electrocatalyst To Enhance Hydrogen Evolution Reaction.
AB - Molybdenum disulfide (MoS2) is a promising catalyst for hydrogen evolution
reaction (HER) because of its unique nature to supply active sites in the
reaction. However, the low density of active sites and their poor electrical
conductivity have limited the performance of MoS2 in HER. In this work, we
synthesized MoS2 nanosheets on three-dimensional (3D) conductive MoO2 via a two
step chemical vapor deposition (CVD) reaction. The 3D MoO2 structure can create
structural disorders in MoS2 nanosheets (referred to as 3D MoS2/MoO2), which are
responsible for providing the superior HER activity by exposing tremendous active
sites of terminal disulfur of S2(-2) (in MoS2) as well as the backbone conductive
oxide layer (of MoO2) to facilitate an interfacial charge transport for the
proton reduction. In addition, the MoS2 nanosheets could protect the inner MoO2
core from the acidic electrolyte in the HER. The high activity of the as
synthesized 3D MoS2/MoO2 hybrid material in HER is attributed to the small onset
overpotential of 142 mV, a largest cathodic current density of 85 mA cm(-2), a
low Tafel slope of 35.6 mV dec(-1), and robust electrochemical durability.
PMID- 26436767
TI - Interleukin-4 receptor-targeted liposomal doxorubicin as a model for enhancing
cellular uptake and antitumor efficacy in murine colorectal cancer.
AB - Our previous studies showed that colorectal tumor has high interleukin-4 receptor
alpha (IL-4Ralpha) expression, whereas adjacent normal tissue has low or no IL
4Ralpha expression. We also observed that human atherosclerotic plaque-specific
peptide-1 (AP1) can specifically target to IL-4Ralpha. In this study, we
investigated the therapeutic efficacy and systemic toxicity of AP1-conjuagted
liposomal doxorubicin. AP1 bound more strongly to and was more efficiently
internalized into IL-4Ralpha-overexpressing CT26 cells than CT26 control cells.
Selective cytotoxicity experiment revealed that AP1-conjugated liposomal
doxorubicin preferentially killed IL-4Ralpha-overexpressing CT26 cells. AP1
conjugated liposomal doxorubicin administered intravenously into mice produced
significant inhibition of tumor growth and showed decreased cardiotoxicity of
doxorubicin. These results indicated that AP1-conjugated liposomal doxorubicin
has a potent and selective anticancer potential against IL-4Ralpha-overexpressing
colorectal cancer cells, thus providing a model for targeted anticancer therapy.
PMID- 26436770
TI - Wave-driven butterfly distribution of Van Allen belt relativistic electrons.
AB - Van Allen radiation belts consist of relativistic electrons trapped by Earth's
magnetic field. Trapped electrons often drift azimuthally around Earth and
display a butterfly pitch angle distribution of a minimum at 90 degrees further
out than geostationary orbit. This is usually attributed to drift shell splitting
resulting from day-night asymmetry in Earth's magnetic field. However, direct
observation of a butterfly distribution well inside of geostationary orbit and
the origin of this phenomenon have not been provided so far. Here we report high
resolution observation that a unusual butterfly pitch angle distribution of
relativistic electrons occurred within 5 Earth radii during the 28 June 2013
geomagnetic storm. Simulation results show that combined acceleration by chorus
and magnetosonic waves can successfully explain the electron flux evolution both
in the energy and butterfly pitch angle distribution. The current provides a
great support for the mechanism of wave-driven butterfly distribution of
relativistic electrons.
PMID- 26436771
TI - Reduced Gut Acidity Induces an Obese-Like Phenotype in Drosophila melanogaster
and in Mice.
AB - In order to identify genes involved in stress and metabolic regulation, we
carried out a Drosophila P-element-mediated mutagenesis screen for starvation
resistance. We isolated a mutant, m2, that showed a 23% increase in survival time
under starvation conditions. The P-element insertion was mapped to the region
upstream of the vha16-1 gene, which encodes the c subunit of the vacuolar-type H+
ATPase. We found that vha16-1 is highly expressed in the fly midgut, and that m2
mutant flies are hypomorphic for vha16-1 and also exhibit reduced midgut acidity.
This deficit is likely to induce altered metabolism and contribute to accelerated
aging, since vha16-1 mutant flies are short-lived and display increases in body
weight and lipid accumulation. Similar phenotypes were also induced by
pharmacological treatment, through feeding normal flies and mice with a carbonic
anhydrase inhibitor (acetazolamide) or proton pump inhibitor (PPI, lansoprazole)
to suppress gut acid production. Our study may thus provide a useful model for
investigating chronic acid suppression in patients.
PMID- 26436772
TI - Correlating Gene-specific DNA Methylation Changes with Expression and
Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1).
AB - DNA methylation serves to regulate gene expression through the covalent
attachment of a methyl group onto the C5 position of a cytosine in a cytosine
guanine dinucleotide. While DNA methylation provides long-lasting and stable
changes in gene expression, patterns and levels of DNA methylation are also
subject to change based on a variety of signals and stimuli. As such, DNA
methylation functions as a powerful and dynamic regulator of gene expression. The
study of neuroepigenetics has revealed a variety of physiological and
pathological states that are associated with both global and gene-specific
changes in DNA methylation. Specifically, striking correlations between changes
in gene expression and DNA methylation exist in neuropsychiatric and
neurodegenerative disorders, during synaptic plasticity, and following CNS
injury. However, as the field of neuroepigenetics continues to expand its
understanding of the role of DNA methylation in CNS physiology, delineating
causal relationships in regards to changes in gene expression and DNA methylation
are essential. Moreover, in regards to the larger field of neuroscience, the
presence of vast region and cell-specific differences requires techniques that
address these variances when studying the transcriptome, proteome, and epigenome.
Here we describe FACS sorting of cortical astrocytes that allows for subsequent
examination of a both RNA transcription and DNA methylation. Furthermore, we
detail a technique to examine DNA methylation, methylation sensitive high
resolution melt analysis (MS-HRMA) as well as a luciferase promoter assay.
Through the use of these combined techniques one is able to not only explore
correlative changes between DNA methylation and gene expression, but also
directly assess if changes in the DNA methylation status of a given gene region
are sufficient to affect transcriptional activity.
PMID- 26436773
TI - Deep-Sea, Deep-Sequencing: Metabarcoding Extracellular DNA from Sediments of
Marine Canyons.
AB - Marine sediments are home to one of the richest species pools on Earth, but
logistics and a dearth of taxonomic work-force hinders the knowledge of their
biodiversity. We characterized alpha- and beta-diversity of deep-sea assemblages
from submarine canyons in the western Mediterranean using an environmental DNA
metabarcoding. We used a new primer set targeting a short eukaryotic 18S sequence
(ca. 110 bp). We applied a protocol designed to obtain extractions enriched in
extracellular DNA from replicated sediment corers. With this strategy we captured
information from DNA (local or deposited from the water column) that persists
adsorbed to inorganic particles and buffered short-term spatial and temporal
heterogeneity. We analysed replicated samples from 20 localities including 2 deep
sea canyons, 1 shallower canal, and two open slopes (depth range 100-2,250 m). We
identified 1,629 MOTUs, among which the dominant groups were Metazoa (with
representatives of 19 phyla), Alveolata, Stramenopiles, and Rhizaria. There was a
marked small-scale heterogeneity as shown by differences in replicates within
corers and within localities. The spatial variability between canyons was
significant, as was the depth component in one of the canyons where it was
tested. Likewise, the composition of the first layer (1 cm) of sediment was
significantly different from deeper layers. We found that qualitative (presence
absence) and quantitative (relative number of reads) data showed consistent
trends of differentiation between samples and geographic areas. The subset of
exclusively benthic MOTUs showed similar patterns of beta-diversity and community
structure as the whole dataset. Separate analyses of the main metazoan phyla (in
number of MOTUs) showed some differences in distribution attributable to
different lifestyles. Our results highlight the differentiation that can be found
even between geographically close assemblages, and sets the ground for future
monitoring and conservation efforts on these bottoms of ecological and economic
importance.
PMID- 26436774
TI - Siaalpha2-3Galbeta1- Receptor Genetic Variants Are Associated with Influenza
A(H1N1)pdm09 Severity.
AB - Different host genetic variants may be related to the virulence and
transmissibility of pandemic Influenza A(H1N1)pdm09, influencing events such as
binding of the virus to the entry receptor on the cell of infected individuals
and the host immune response. In the present study, two genetic variants of the
ST3GAL1 gene, which encodes the Siaalpha2-3Galbeta1- receptor to which influenza
A(H1N1)pdm09 virus binds for entry into the host cell, were investigated in an
admixed Brazilian population. First, the six exons encoding the ST3GAL1 gene were
sequenced in 68 patients infected with strain A(H1N1)pdm09. In a second phase of
the study, the rs113350588 and rs1048479 polymorphisms identified in this sample
were genotyped in a sample of 356 subjects from the northern and northeastern
regions of Brazil with a diagnosis of pandemic influenza. Functional analysis of
the polymorphisms was performed in silico and the influence of these variants on
the severity of infection was evaluated. The results suggest that rs113350588 and
rs1048479 may alter the function of ST3GAL1 either directly through splicing
regulation alteration and/or indirectly through LD with SNP with regulatory
function. In the study the rs113350588 and rs1048479 polymorphisms were in
linkage disequilibrium in the population studied (D' = 0.65). The GC haplotype
was associated with an increased risk of death in subjects with influenza (OR =
4.632, 95% CI = 2.10;1.21). The AT haplotype was associated with an increased
risk of severe disease and death (OR = 1.993, 95% CI = 1.09;3.61 and OR 4.476,
95% CI = 2.37;8.44, respectively). This study demonstrated for the first time the
association of ST3GAL1 gene haplotypes on the risk of more severe disease and
death in patients infected with Influenza A(H1N1)pdm09 virus.
PMID- 26436775
TI - Indirect Energy Flows in Niche Model Food Webs: Effects of Size and Connectance.
AB - Indirect interactions between species have long been of interest to ecologists.
One such interaction type takes place when energy or materials flow via one or
more intermediate species between two species with a direct predator-prey
relationship. Previous work has shown that, although each such flow is small,
their great number makes them important in ecosystems. A new network analysis
method, dynamic environ approximation, was used to quantify the fraction of
energy flowing from prey to predator over paths of length greater than 1 (flow
indirectness or FI) in a commonly studied food web model. Web structure was
created using the niche model and dynamics followed the Yodzis-Innes model. The
effect of food web size (10 to 40 species) and connectance (0.1 to 0.48) on FI
was examined. For each of 250 model realizations run for each pair of size and
connectance values, the FI of every predator-prey interaction in the model was
computed and then averaged over the whole network. A classification and
regression tree (CART) analysis was then used to find the best predictors of FI.
The mean FI of the model food webs is 0.092, with a standard deviation of 0.0279.
It tends to increase with system size but peaks at intermediate connectance
levels. Of 27 potential predictor variables, only five (mean path length,
dominant eigenvalue of the adjacency matrix, connectance, mean trophic level and
fraction of species belonging to intermediate trophic levels) were selected by
the CART algorithm as best accounting for variation in the data; mean path length
and the dominant eigenvalue of the adjacency matrix were dominant.
PMID- 26436776
TI - A quantum dot single-photon source with on-the-fly all-optical polarization
control and timed emission.
AB - Sources of single photons are key elements for applications in quantum
information science. Among the different sources available, semiconductor quantum
dots excel with their integrability in semiconductor on-chip solutions and the
potential that photon emission can be triggered on demand. Usually, the photon is
emitted from a single-exciton ground state. Polarization of the photon and time
of emission are either probabilistic or pre-determined by electronic properties
of the system. Here, we study the direct two-photon emission from the biexciton.
The two-photon emission is enabled by a laser pulse driving the system into a
virtual state inside the band gap. From this intermediate state, the single
photon of interest is then spontaneously emitted. We show that emission through
this higher-order transition provides a versatile approach to generate a single
photon. Through the driving laser pulse, polarization state, frequency and
emission time of the photon can be controlled on-the-fly.
PMID- 26436777
TI - Bisphenol A and other bisphenol analogues including BPS and BPF in surface water
samples from Japan, China, Korea and India.
AB - Concentrations of eight bisphenol analogues (BPs) including BPA, BPS, and BPF
were determined in surface waters collected from select rivers in Japan, Korea,
China, and India. BPA was found at a concentration in the range of several tens
to several hundreds of nanograms per liter in most of the rivers surveyed and
some of the highest concentrations (54-1950 ng/L) were found in rivers in
Chennai, India. Concentrations of BPF were one to two orders of magnitude higher
than those of BPA in river and sea waters collected from Japan, Korea and China,
which suggested that BPF is a major contaminant in surface waters in several
Southeast Asian countries. BPF concentrations as high as 2850 ng/L were found in
the Tamagawa River in Japan. The flux of BPs through riverine discharges into
Tokyo Bay was calculated to be approximately 5.5 t per year. Based on the flux
estimates and the mass of BPF found in water column and sediment in Tokyo Bay, it
was found that BPF degrades faster than BPA in the environment. Elevated
concentrations of BPF found in surface waters suggest the need for further
studies to determine the fate and toxicity of this compound.
PMID- 26436778
TI - Synthesis of Tricyclic Spiranoid Lactones via I2/Sm(II)- and I2/Pd(0)-Mediated
Cyclizations of a Common Cycloalkylmethylene Precursor.
AB - A general synthesis of phylogenetically and structurally different tricyclic
angularly fused spiranoid lactones, frequently observed as scaffold segments of
various biochemical compounds and drugs of natural origin, is demonstrated via
controlled cyclization of simple and easily accessible cycloalkylmethylene key
precursors. The rapid composition of the key architecture yields an assembly of
stable bicyclic iodolactones, which are converted to form a wide range of
angularly fused tricyclic scaffolds.
PMID- 26436779
TI - Tomato yellow leaf curl virus differentially influences plant defence responses
to a vector and a non-vector herbivore.
AB - Plants frequently engage in simultaneous interactions with diverse classes of
biotic antagonists. Differential induction of plant defence pathways by these
antagonists, and interactions between pathways, can have important ecological
implications; however, these effects are currently not well understood. We
explored how Tomato yellow leaf curl virus (TYLCV) influenced the performance of
its vector (Bemisia tabaci) and a non-vector herbivore (Tetranychus urticae)
occurring separately or together on tomato plants (Solanum lycopersicum). TYLCV
enhanced the performance of B. tabaci, although this effect was statistically
significant only in the absence of T. urticae, which adversely affected B. tabaci
performance regardless of infection status. In contrast, the performance of T.
urticae was enhanced (only) by the combined presence of TYLCV and B. tabaci.
Analyses of phytohormone levels and defence gene expression in wild-type tomatoes
and various plant-defence mutants indicate that the enhancement of herbivore
performance (for each species) entails the disruption of downstream defences in
the jasmonic acid (JA) pathway. For T. urticae, this disruption appears to
involve antagonistic effects of salicylic acid (SA), which is cumulatively
induced to high levels by B. tabaci and TYLCV. In contrast, TYLCV was found to
suppress JA-mediated responses to B. tabaci via mechanisms independent of SA.
PMID- 26436780
TI - [Controversy regarding the use of thimerosal in vaccines: evidence for decision
making].
PMID- 26436781
TI - [Primary resistance to anti tuberculosis drugs in Chile 2011-2012].
AB - This publication presents the results of the Chilean initial study of resistance
to first line anti-tuberculous drugs. The study was carried out between 2011 and
2012 by the National Reference Laboratory of the Institute of Public Health, as
part of the Drug Surveillance Resistance in tuberculosis (TB) promoted by the
World Health Organization. METHODOLOGY: Cross-sectional study performed using
cluster sampling, representative of the entire country as recommended by the
World Health Organization. Susceptibility testing to isoniazid, rifampicin,
streptomycin, ethambutol and pyrazinamide was performed through the proportion
method or Wayne's enzymatic method, as appropriate. RESULTS: 594 susceptibility
tests were performed, showing an overall level of TB drug resistance of 8.6% and
a prevalence of multidrug resistance of 1.3%. Indeed, the study showed a decrease
in streptomycin resistance and an increase of isoniazid resistance in both mono
resistance and accumulated resistance compared to previous studies. No cases of
mono-resistance to rifampicin were detected. CONCLUSION: An increased resistance
to anti-TB drugs in Chile is observed, which despite being still low, is no less
worrisome. Since 2014 the monitoring of drug resistance to TB is universally
performed to avoid sub - diagnosis and treat each case according to the
susceptibility profile.
PMID- 26436782
TI - [Risk factor of intestinal colonization with vancomycin resistant Enterococcus
spp in hospitalized pediatric patients with oncological disease].
AB - BACKGROUND: The isolation of vancomycin-resistant Enterococcus spp (ERV) has
increased significantly within the last few years, along with the risk of
infection and dissemination of these bacteria. Our aim was to determine risk
factors (RF) for intestinal colonization in hospitalized pediatric patients with
oncological disease at Hospital de Ninos Roberto del Rio. METHODS: Between
January 2012 and December 2013 a transversal study was performed with 107 rectal
swabs and processed with a PCR for ERV. The patients were classified as
"colonized with ERV" and "not colonized with ERV" and we evaluated possible RF
for intestinal colonization in both groups. RESULTS: VRE colonization was found
in 51 patients (52%). The median of time elapsed between oncological diagnosis
and VRE colonization was 35 days. The significant RF associated with VRE
colonization were days of hospitalization prior to study, neutropenia and
treatment with antibiotics within 30 days prior to study and mucositis.
CONCLUSIONS: According to the RF revealed in this study we may suggest prevention
standards to avoid ERV colonization. This is the first investigation in our
country in hospitalized pediatric patients with oncological disease and processed
with a multiplex PCR for ERV, therefore it is a great contribution about this
subject in Chile.
PMID- 26436783
TI - [Use of mass spectrometry for rapid diagnosis of positive blood cultures:
Validation of a local algorythm].
AB - Mass spectrometry (MS) is used in identification of positive blood culture, a
contribution in the clinical management of septic patients. The protocol is labor
intensive and disrupts the normal workflow in a clinical laboratory. We intended
to make rapid diagnosis by using MS directly from shortly incubated blood agar
plates (4 to 6 hours) comparing with results of the conventional method (MC). We
worked in parallel 145 positive blood cultures, with correct identification by
short method in 79% of cases. We observed better yield with non carbon bottles
and with gramnegative rods. With this information we designed a rapid
identification algorithm using MS, which allows advancing diagnosis in 12-16
hours, without increasing to the costs or work load, since extraction protocol is
not used.
PMID- 26436784
TI - [Parasites of zoonotic importance in dog feces collected in parks and public
squares of the city of Los Angeles, Bio-Bio, Chile].
AB - INTRODUCTION: The contamination of public squares and parks with dog feces poses
a risk to the population, since it may contain parasitic elements of zoonotic
importance. AIM: To identify human pathogenic parasites in samples of dog feces
collected from parks and public squares. METHODS: 452 fecal dog samples collected
from 65 squares and public parks were analyzed using the technique of Burrows.
RESULTS: 60% (39/65) of the samples contained some parasitic forms with a
zoonotic potential. Parasitic taxa with zoonotic risk were Toxocara sp.,
Ancylostoma sp., Dipylidium caninum, Giardia sp., Taenia sp., Toxascaris sp.,
Strongyloides sp., and Uncinaria sp. CONCLUSION: The detected parasites present a
risk to human health, so it seems necessary to implement health education
activities in the community, develop deworming plans, and control the canine
overpopulation.
PMID- 26436785
TI - [Effects in the adherence treatment and psychological adjustment after the
disclosure of HIV/AIDS diagnosis with the "DIRE" clinical model in Colombian
children under 17].
AB - BACKGROUND: A study in five Colombian cities in 2006, confirms the findings of
other international studies: the majority of HIV-positive children not know their
diagnosis, caregivers are reluctant to give this information because they believe
that the news will cause emotional distress to the child becoming primary purpose
of this study to validate a model of revelation. MATERIALS AND METHODS: We
implemented a clinical model, referred to as: "DIRE" that hypothetically had
normalizing effects on psychological adjustment and adherence to antiretroviral
treatment of HIV seropositive children, using a quasi-experimental design. Test
were administered (questionnaire to assess patterns of disclosure and non
disclosure of the diagnosis of VIH/SIDA on children in health professionals and
participants caregivers, Family Apgar, EuroQol EQ- 5D, MOS Social Support Survey
Questionnaire Information treatment for VIH/SIDA and child Symptom Checklist
CBCL/6-18 adapted to Latinos) before and after implementation of the model to 31
children (n: 31), 30 caregivers (n: 30) and 41 health professionals. Data
processing was performed using the Statistical Package for the Social Science
version 21 by applying parametric tests (Friedman) and nonparametric (t Student).
RESULTS: No significant differences in adherence to treatment (p=0.392), in the
psychological adjustment were found positive significant differences at follow
ups compared to baseline 2 weeks (p: 0.001), 3 months (p: 0.000) and 6 months (p:
0.000). CONCLUSIONS: The clinical model demonstrated effectiveness in normalizing
of psychological adjustment and maintaining treatment compliance. The process
also generated confidence in caregivers and health professionals in this
difficult task.
PMID- 26436786
TI - [Measles: the disease, epidemiology, history and vaccination programs in Chile].
AB - Measles, one of most important inmuno-preventable diseases, remains as a
worldwide concern issue with an important morbidity and mortality. Particularly
in the America region declared free of measles in 2010 by WHO, they still appear
imported cases that origin outbreaks of variable magnitude in susceptible
subjects usually none vaccinated which is the current situation in Santiago, the
capital city of Chile. In this review we present characteristics of the
etiological agent, the disease, epidemiological aspects with national historical
focus, impact of immunization programs and outbreaks in Chile, in order to
contribute to knowledge and management of this always present public health
problem.
PMID- 26436787
TI - [Streptococcus gallolyticus (ex S. bovis) bacteremia and its relationship with
colonic or hepatobiliary disease and endocarditis].
AB - BACKGROUND: Bacteremia due to Streptococcus bovis (now S. gallolyticus) has been
traditionally associated to colon or hepatobiliar disease and endocarditis but
there is no information on this matter in Chile. AIMS: To describe clinical
features of adult patients suffering bacteremia by S. bovis/S. gallolyticus,
identify the source of the bacteremia and the frequency of endocarditis. METHODS:
Retrospective-descriptive study using laboratory records. RESULTS: Between
January 2003 and August 2014, 23 S. bovis/S. gallolyticus bacteremic events were
identified among 22 patients. Mean age was 72.7 years (range 46-96). Co
morbidities were frequent (9.1 to 47.6%). The primary source of bacteremia was
intestinal in 52.2%; hepatobiliar in 17.4% and in 34.8% it was not elucidated.
Six patients had infective endocarditis (26.1%) and one patient had
espondylodiscitis (4.3%). S. bovis represented 39.1% of isolates (all until
2008), S. gallolyticus subsp pasteurianus 39.1% and, S. gallolyticus subsp
infantarius and S. gallolyticus subsp gallolyticus 8.7% each one, respectively.
Association studies between the bacteremic source or endocarditis with specific
S. gallolyticus subspecies were limited by the small number of isolates. Seven
patients (30.4%) underwent surgical interventions. In-hospital mortality reached
21.7% (n=5). CONCLUSIONS: Although infrequent, bacteremic events by S.
gallolyticus/S. bovis have increased in-hospital mortality, require surgical
intervention and affect older patients with co-morbidities. Near two-thirds
suffer from colonic or hepatobiliary disease that act as the primary source of
bacteremia. In addition, near one fourth is affected by infective endocarditis.
Detection of S. gallolyticus/S. bovis in blood cultures prompts a thorough
clinical evaluation in order to clarify the source of the bloodstream infection
and the presence of complications.
PMID- 26436788
TI - [Prognostic factors in adult patients hospitalized for pneumonia caused by
Legionella pneumophila].
AB - INTRODUCTION: Legionellosis is a multisystem bacterial disease, which causes
pneumonia with high mortality in patients with comorbidity and admitted in
intensive care units (ICU). OBJECTIVE: Determine predictors of mortality or ICU
admission. METHODS: Retrospective follow-up of patients diagnosed with Legionella
pneumophila pneumonia in Complexo Hospitalario Universitario de A Coruna. Period
2000-2013 (n=240). Analysis of multivariate logistic regression was performed.
RESULTS: Mean age was 57.2+/-15.4 years old, 88.3% were male. Average score of
comorbidity (Charlson score) was 2.3+/-2.3. There was a clear seasonal variation.
Predominant symptoms were fever (92.5%), dry cough (38.1%) and dyspnea (33.9%).
Creatinine clearance was lower than 60 mL/min/1.73 m2 in 29.7% and sodium<135
mEq/l in 58.3%. Admission to ICU rate was 16.3% and 10.8% needs mechanical
ventilation. Inhospital mortality rate was 4.6%, rising to 23.1% in patients
admitted to ICU. Variables associated to predict ICU admission were age
(OR=0.96), liver disease (OR=7.13), dyspnea (OR=4.33), delirium (OR=5.86) and
high levels of lactatedehydrogenase (OR=1.002). Variables associated with
inhospital mortality were Charlson index (OR=1.70), mechanical ventilation
(OR=31.44) and high levels of lactatedehydrogenase (OR=1.002). DISCUSSION:
Younger patients with liver disease, dyspnea and confusion are more likely to be
admitted to ICU. Comorbidity, mechanical ventilation and elevated LDH levels are
associated with higher mortality rate.
PMID- 26436789
TI - [Pseudomonas (Flavimonas) oryzihabitans].
PMID- 26436790
TI - [Early neonatal sepsis, incidence and associated risk factors in a public
hospital in western Mexico].
AB - BACKGROUND: Early neonatal sepsis (EOS) is the second leading cause of death in
the first week of life. Epidemiology differs in developed and developing
countries. AIM: To describe the epidemiology of EOS among newborn patients in a
public hospital in western Mexico. METHODS: A prospective cohort study was
performed in newborns of Nuevo Hospital Civil de Guadalajara "Dr. Juan I
Menchaca". EOS was diagnosed with blood cultures or cultures of cerebrospinal
fluid within the first 72 h of life. We analyzed risk factors (RF) by
multivariate analysis with logistic regression. RESULTS: We identified an EOS
incidence of 4.7 events per 1,000 live births. Seventy two percent of the
isolated bacteria were gram negative bacilli. Factors associated with EOS were
maternal age<=15 years (OR 3.50; 95% CI 1.56-7.85), rupture of membranes>18 h (OR
2.65; 95% CI 1.18-5.92), maternal fever (OR 6.04; 95% CI 1.54-23.6), birth
weight<=2,500 g (OR 4.82; 95% CI 2.38-9.75) and gestational age<37 weeks (OR
3.14; 95% CI 1.58-6.22). CONCLUSIONS: In addition to the RF known for EOS an
independent association was observed with maternal age<=15 years.
PMID- 26436791
TI - [Beginning of the Microbiology education in Chile: formation centers].
AB - The first Chair of Microbiology in Chile was created in the School of Medicine of
the Canadilla at the University of Chile in 1892. Dr. Alejandro del Rio Soto
Aguilar was its first Professor. For almost three decades it was the only
educational center for microbiologists in Chile. Among them were the first
Professors of the new School of Medicine of the Catholic University of Chile and
of the University of Concepcion.
PMID- 26436792
TI - [Stereotactic aspiration of Spirometra mansonides larvae].
AB - Brain sparganosis is a non-common parasite infection by Diphyllobothrium or
Spirometra mansonoides larvae. This last one is responsible for most of the
infestations in humans. We report a 19 years male patient bearer of a brain
sparganosis. The patient presented with headache and left hemiparesis. CT
diagnosis of right thalamic lesions was made and aspiration biopsy was performed
using stereotactic system, obtaining a whole and death larvae. Histopathology
confirms a CNS parasitism and it was treated initially with albendazol. ELISA
test confirmed Spirometra spp. infestation. The patient developed asymptomatic
with total remission of the lesions. It constitutes the second report in Cuba of
brain sparganosis.
PMID- 26436793
TI - [The sparganosis].
PMID- 26436794
TI - [Successful treatment of a persistent rhino-cerebral mucormycosis in a pediatric
patient with a debut of acute lymphoblastic leukemia].
AB - The fungi of the order Mucorales cause mucormycosis, which usually presents as an
invasive fungal disease with rapid angioinvasion in immunocompromised patients.
Rhinocerebral is the most common presentation. The lipid formulations of
amphotericin B are used as primary treatment in invasive mucormycosis; the
combined use of posaconazole could allow a reduction in the dose of amphotericin
B improving tolerance and adherence to treatment. Caspofungin and amphotericin B
association has been shown to be synergistic in vitro and effective in murine
models. We present the case of a preschool patient that during the debut of acute
lymphoblastic leukemia developed a rhinocerebral mucormycosis successfully
responding to antifungal treatment with the combination of liposomal amphotericin
and caspofungin.
PMID- 26436795
TI - [Listeria monocytogenes meningitis in immunocompetent children: unpasteurized
cheese likely cause of infection].
AB - Listeria meningoencephalitis is a rare condition, occurring mainly in
immunocompromised patients. We present two cases of Listeria monocytogenes
meningoencephalitis in immunocompetent children, with successful treatment with
betalactam/aminoglycoside combination. Unpasteurized cheese was postulated as the
source of infection.
PMID- 26436796
TI - [Cutaneous loxoscelism mainly edematous: a case report].
AB - In Chile, loxoscelism is caused by the bite of the Loxosceles laeta spider. The
clinical presentation has two different forms: cutaneous loxoscelism (CL) and
vicero-cutaneous loxoscelism, which is less frequent. Cutaneous loxoscelism
includes an uncommon clinical variation (4%), called CL with edematous
predominance (CLEP). We present a 5-year-old patient with sudden pain and edema
on his right eyelid associated with fever, which progressed rapidly involving the
right hemifacial area, frontal region, and left eyelid. Angioedema and pre
orbital cellulitis were discarded and CLEP was suspect. Cutaneous loxoscelism
with an edematous predominance is self-limited, benign and with little or no
necrotic injury due to the edema, which dilutes the toxin-induced enzymatic
process causing necrosis. As in the reported cases it usually responds well to
medical treatment and does not cause visceral involvement.
PMID- 26436797
TI - [Pulmonary non invasive infection by Scedosporium apiospermum].
AB - We reported a case of non-invasive pulmonary infection by Scedosporium
apiospermum in 67 years old female with bronchiectasis and caverns secondary to
tuberculosis. Diagnosis was made with lung CT and bronchial lavage cultures. The
patient was initially treated with itraconazole for six weeks without success and
then voriconazole for 16 weeks, with good clinical response.
PMID- 26436798
TI - [Severe acute disseminated encephalomyelitis associated with parainfluenza 3
infection: Case report].
AB - Disseminated encephalomyelitis (ADEM) is an infrequent condition with
considerable morbidity and mortality in adult patients. It requires a high level
of suspicion and diagnosis emerges by gathering clinical information, laboratory
exams and images studies. ADEM is related to an immunological phenomena occurring
after a bacterial/viral infection or recent vaccination. Glucocorticoids are the
first line treatment, reserving immunoglobulins and plasmapheresis to refractory
cases. We report a male patient aged 25, with ADEM associated to parainfluenza 3
virus respiratory infection that required mechanical ventilation and that had a
complete recovery only after plasmapheresis.
PMID- 26436799
TI - [Hepatitis E virus seroprevalence: a reappraisal].
AB - Reported seroprevalence of hepatitis E virus (HEV) in developed countries is
between 0.3-53%. Published data relies on the assays used and its technical
performance. Sensitivity on new available tests has improved, which has changed
HEV seroprevalence around the world. We re-evaluated retrospectively, 178 serum
samples of patients with previous anti HEV IgG determination between 2009 and
2012. Initial analysis was performed with ELISA kit Genelabs (Singapore), with
7.3% positivity. The reevaluation was done with ELISA kit AccuDiag TM HEV-IgG
(Diagnostic Automation, United States), with reported sensitivity and specificity
over 99.8%. With the new assay, 32.6% positive samples were found, significantly
greater to the previous result (p<0.001) (4.5 times more). There were no
differences in gender but a significant association between age and HEV IgG
seropositivity was found (p<0.001). This suggests that previous testing might
have underestimated HEV seroprevalence in Chile, which should be reevaluated
using the new available test.
PMID- 26436800
TI - [Erratum].
PMID- 26436801
TI - [Thimerosal into vaccines: the law and the evidence].
PMID- 26436802
TI - [Elite controller cured of hepatitis C virus after 14 weeks of telaprevir-based
triple therapy].
PMID- 26436803
TI - [Acquisition of multi-resistant enterobacteriaceae in travelers to tropical
zones].
PMID- 26436804
TI - The Foraging Ecology of the Endangered Cape Verde Shearwater, a Sentinel Species
for Marine Conservation off West Africa.
AB - Large Marine Ecosystems such as the Canary Current system off West Africa
sustains high abundance of small pelagic prey, which attracts marine predators.
Seabirds are top predators often used as biodiversity surrogates and sentinel
species of the marine ecosystem health, thus frequently informing marine
conservation planning. This study presents the first data on the spatial (GPS
loggers) and trophic (stable isotope analysis) ecology of a tropical seabird-the
endangered Cape Verde shearwater Calonectris edwardsii-during both the incubation
and the chick-rearing periods of two consecutive years. This information was
related with marine environmental predictors (species distribution models),
existent areas of conservation concern for seabirds (i.e. marine Important Bird
Areas; marine IBAs) and threats to the marine environment in the West African
areas heavily used by the shearwaters. There was an apparent inter-annual
consistency on the spatial, foraging and trophic ecology of Cape Verde
shearwater, but a strong alteration on the foraging strategies of adult breeders
among breeding phases (i.e. from incubation to chick-rearing). During incubation,
birds mostly targeted a discrete region off West Africa, known by its enhanced
productivity profile and thus also highly exploited by international industrial
fishery fleets. When chick-rearing, adults exploited the comparatively less
productive tropical environment within the islands of Cape Verde, at relatively
close distance from their breeding colony. The species enlarged its trophic niche
and increased the trophic level of their prey from incubation to chick-rearing,
likely to provision their chicks with a more diversified and better quality diet.
There was a high overlap between the Cape Verde shearwaters foraging areas with
those of European shearwater species that overwinter in this area and known areas
of megafauna bycatch off West Africa, but very little overlap with existing
Marine Important Bird Areas. Further investigation on the potential nefarious
effects of fisheries on seabird communities exploiting the Canary Current system
off West Africa is needed. Such negative effects could be alleviated or even
dissipated if the 'fisheries-conservation hotspots' identified for the region,
would be legislated as Marine Protected Areas.
PMID- 26436805
TI - Biliary/Pancreas.
PMID- 26436806
TI - Stomach.
PMID- 26436809
TI - Clinical Vignettes/Case Reports - Biliary/Pancreas.
PMID- 26436811
TI - Colorectal Cancer Prevention.
PMID- 26436810
TI - Colon.
PMID- 26436812
TI - Endoscopy.
PMID- 26436813
TI - Endoscopy Video Forum.
PMID- 26436814
TI - Esophagus.
PMID- 26436815
TI - Functional Bowel Disease.
PMID- 26436816
TI - Inflammatory Bowel Disease.
PMID- 26436817
TI - Liver.
PMID- 26436818
TI - Outcomes Research.
PMID- 26436819
TI - Pediatrics.
PMID- 26436820
TI - Small Intestine/Unclassified.
PMID- 26436821
TI - Effect of Jig Design and Assessment of Stress Distribution in Testing Metal
Ceramic Adhesion.
AB - PURPOSE: In testing adhesion using shear bond test, a combination of shear and
tensile forces occur at the interface, resulting in complex stresses. The jig
designs used for this kind of test show variations in published studies,
complicating direct comparison between studies. This study evaluated the effect
of different jig designs on metal-ceramic bond strength and assessed the stress
distribution at the interface using finite element analysis (FEA). MATERIALS AND
METHODS: Metal-ceramic (Metal: Ni-Cr, Wiron 99, Bego; Ceramic: Vita Omega 900,
Vita) specimens (N = 36) (diameter: 4 mm, veneer thickness: 4 mm; base diameter:
5 mm, thickness: 1 mm) were fabricated and randomly divided into three groups (n
= 12 per group) to be tested using one of the following jig designs: (a) chisel
(CH) (ISO 11405), (b) steel strip (SS), (c) piston (PI). Metal-ceramic interfaces
were loaded under shear until debonding in a universal testing machine (0.5
mm/min). Failure types were evaluated using scanning electron microscopy (SEM).
FEA was used to study the stress distribution using different jigs. Metal-ceramic
bond strength data (MPa) were analyzed using ANOVA and Tukey's tests (alpha =
0.05). RESULTS: The jig type significantly affected the bond results (p =
0.0001). PI type of jig presented the highest results (MPa) (p < 0.05) (58.2 +/-
14.8), followed by CH (38.7 +/- 7.6) and SS jig type (23.3 +/- 4.2) (p < 0.05).
Failure types were exclusively a combination of cohesive failure in the opaque
ceramic and adhesive interface failure. FEA analysis indicated that the SS jig
presented slightly more stress formation than with the CH jig. The PI jig
presented small stress concentration with more homogeneous force distribution
compared to the CH jig where the stress concentrated in the area where the force
was applied. CONCLUSION: Metal-ceramic bond strength was affected by the jig
design. Accordingly, the results of in vitro studies on metal-ceramic adhesion
should be evaluated with caution. CLINICAL SIGNIFICANCE: When adhesion of ceramic
materials to metals is evaluated in in vitro studies, it should be noted that the
loading jig type affects the results. Clinical observations should report on the
location and type of ceramic fractures in metal-ceramic reconstructions so that
the most relevant test method can be identified.
PMID- 26436822
TI - Use of terrestrial field studies in the derivation of bioaccumulation potential
of chemicals.
AB - Field-based studies are an essential component of research addressing the
behavior of organic chemicals, and a unique line of evidence that can be used to
assess bioaccumulation potential in chemical registration programs and aid in
development of associated laboratory and modeling efforts. To aid scientific and
regulatory discourse on the application of terrestrial field data in this manner,
this article provides practical recommendations regarding the generation and
interpretation of terrestrial field data. Currently, biota-to-soil-accumulation
factors (BSAFs), biomagnification factors (BMFs), and bioaccumulation factors
(BAFs) are the most suitable bioaccumulation metrics that are applicable to
bioaccumulation assessment evaluations and able to be generated from terrestrial
field studies with relatively low uncertainty. Biomagnification factors
calculated from field-collected samples of terrestrial carnivores and their prey
appear to be particularly robust indicators of bioaccumulation potential. The use
of stable isotope ratios for quantification of trophic relationships in
terrestrial ecosystems needs to be further developed to resolve uncertainties
associated with the calculation of terrestrial trophic magnification factors
(TMFs). Sampling efforts for terrestrial field studies should strive for
efficiency, and advice on optimization of study sample sizes, practical
considerations for obtaining samples, selection of tissues for analysis, and data
interpretation is provided. Although there is still much to be learned regarding
terrestrial bioaccumulation, these recommendations provide some initial guidance
to the present application of terrestrial field data as a line of evidence in the
assessment of chemical bioaccumulation potential and a resource to inform
laboratory and modeling efforts.
PMID- 26436823
TI - Spectral Inspections on Molecular Configurations of Nile Blue A Adsorbed on the
Elementary Clay Sheets.
AB - Studies on the configuration of dye molecules are of great importance in
revealing origins of the electronic bands as well as understanding their
transitions. In this work, we utilized dye molecules named Nile blue A, which are
a type of oxazine dyes, to study the molecular configurations when they are
transferred from solutions to a solid surface. The Langmuir-Blodgett (LB)
technique was employed to construct such an interface where the interaction
between the dye molecules and solid supports can be pursued. Hybrid films were
prepared via the LB depositions, and the dye molecules were assembled on the
elementary clay sheets (laponite, saponite). The configuration of Nb reflected by
the molecular orientation, packing density, phase behavior, and variances of the
surface tension has been derived. The ex situ spectroscopy characterizations such
as UV-vis absorption, fluorescence emission, and excitation spectra were carried
out on these LB films to reveal the fact that the adsorbed Nb molecules are
mainly assembled in two types of configurations. Adsorbed state I was found to be
achieved at high concentrations (1-10 ppm) of clay dispersions and low surface
pressure (~5 mN/m). In this state the anionic oxazine rings of Nb are adsorbed on
clay sheets sharing a large lift-off area. This configuration gives allowable
fluorescence (lambda = 550 nm). Lower clay concentration (<1 ppm) and high
surface pressure (10-30 mN/m) yield the adsorbed state II in which the oxazine
chromophores were arranged in a side-by-side style, and the dye molecules stand
perpendicularly to the clay sheets. This conformation exhibits no
photoluminescence.
PMID- 26436824
TI - Imazamox-clay complexes with chitosan- and iron(III)-modified smectites and their
use in nanoformulations.
AB - BACKGROUND: Imazamox is an ionisable herbicide, weakly retained and with high
soil vertical mobility, that is used for the control of the root-parasitic plants
Orobanche spp. A natural smectite (SW) modified with the biopolymer chitosan (Ch)
or with Fe(3+) cation was assayed as adsorbent or carrier for imazamox controlled
release formulations (CRFs). RESULTS: The greatest adsorption (74%) was observed
for SWFe at high initial concentration (500 uM) and low pH (4.3). The interaction
mechanism of imazamox on SWFe implies interlayer polar adsorption, followed by
protonation of the imidazolinone ring, whereas ionic, polar and hydrophobic
interactions seemed to occur in imazamox adsorption on SWCh. The herbicide
release into water was inversely related to the strength of the imazamox-clay
interactions and ranged in the first 10 min for imazamox-SWFe and imazamox-SWCh
complexes from 27 to 75%, whereas commercial imazamox released 86%. The imazamox
SWCh weak complex (SWCh6 WC) showed similar herbicidal activity to the commercial
formulation but produced a reduction of 15% in the total soil leaching losses and
a reduction of 40% in the peak maximum concentration in soil column leachates.
CONCLUSION: The imazamox-clay weak complex (WC) of SWFe and SWCh and the strong
complex (SC) with SWCh showed appropriate behaviour as nanopesticides or smart
delivery systems to be incorporated in CRFs. (c) 2015 Society of Chemical
Industry.
PMID- 26436825
TI - Complete mitochondrial genome of Coregonus cluncaformis.
AB - The complete mitochondrial genome of Coregonus cluncaformis was determined in
this study. The mitogenome is 16 736 bp in length and contains 1D-loop region, 2
ribosomal RNA genes, 22 transfer RNA genes, and 13 protein-coding genes. The
overall base composition of the heavy strand is 26.79% for A, 29.49% for C,
18.07% for G and 25.66% for T, The percentage of G + C content is 47.56%. This is
the first time of the mitochondrial genome sequencing for C. cluncaformis in this
study.
PMID- 26436826
TI - Polymerase delta replicates both strands after homologous recombination-dependent
fork restart.
AB - To maintain genetic stability, DNA must be replicated only once per cell cycle,
and replication must be completed even when individual replication forks are
inactivated. Because fork inactivation is common, passive convergence of an
adjacent fork is insufficient to rescue all inactive forks. Thus, eukaryotic
cells have evolved homologous recombination-dependent mechanisms to restart
persistent inactive forks. Completing DNA synthesis via homologous recombination
restarted replication (HoRReR) ensures cell survival, but at a cost. One such
cost is increased mutagenesis because HoRReR is more error prone than canonical
replication. This increased error rate implies the HoRReR mechanism is distinct
from that of a canonical fork. Here we demonstrate, in Schizosaccharomyces pombe,
that a DNA sequence duplicated by HoRReR during S phase is replicated
semiconservatively, but both the leading and lagging strands are synthesized by
DNA polymerase delta.
PMID- 26436827
TI - Rif1 binds to G quadruplexes and suppresses replication over long distances.
AB - Rif1 regulates replication timing and repair of double-strand DNA breaks. Using a
chromatin immunoprecipitation-sequencing method, we identified 35 high-affinity
Rif1-binding sites in fission yeast chromosomes. Binding sites tended to be
located near dormant origins and to contain at least two copies of a conserved
motif, CNWWGTGGGGG. Base substitution within these motifs resulted in complete
loss of Rif1 binding and in activation of late-firing or dormant origins located
up to 50 kb away. We show that Rif1-binding sites adopt G quadruplex-like
structures in vitro, in a manner dependent on the conserved sequence and on other
G tracts, and that purified Rif1 preferentially binds to this structure. These
results suggest that Rif1 recognizes and binds G quadruplex-like structures at
selected intergenic regions, thus generating local chromatin structures that may
exert long-range suppressive effects on origin firing.
PMID- 26436828
TI - Structural basis of template-boundary definition in Tetrahymena telomerase.
AB - Telomerase is required to maintain repetitive G-rich telomeric DNA sequences at
chromosome ends. To do so, the telomerase reverse transcriptase (TERT) subunit
reiteratively uses a small region of the integral telomerase RNA (TER) as a
template. An essential feature of telomerase catalysis is the strict definition
of the template boundary to determine the precise TER nucleotides to be reverse
transcribed by TERT. We report the 3-A crystal structure of the Tetrahymena TERT
RNA-binding domain (tTRBD) bound to the template boundary element (TBE) of TER.
tTRBD is wedged into the base of the TBE RNA stem-loop, and each of the flanking
RNA strands wraps around opposite sides of the protein domain. The structure
illustrates how the tTRBD establishes the template boundary by positioning the
TBE at the correct distance from the TERT active site to prohibit copying of
nontemplate nucleotides.
PMID- 26436829
TI - Excited-State Deactivation of Branched Phthalocyanine Compounds.
AB - The excited-state relaxation dynamics and chromophore interactions in two
phthalocyanine compounds (bis- and trisphthalocyanines) are studied by using
steady-state and femtosecond transient absorption spectral measurements, where
the excited-state energy-transfer mechanism is explored. By exciting
phthalocyanine compounds to their second electronically excited states and
probing the subsequent relaxation dynamics, a multitude of deactivation pathways
are identified. The transient absorption spectra show the relaxation pathway from
the exciton state to excimer state and then back to the ground state in
bisphthalocyanine (bis-Pc). In trisphthalocyanine (tris-Pc), the monomeric and
dimeric subunits are excited and the excitation energy transfers from the
monomeric vibrationally hot S1 state to the exciton state of a pre-associated
dimer, with subsequent relaxation to the ground state through the excimer state.
The theoretical calculations and steady-state spectra also show a face-to-face
conformation in bis-Pc, whereas in tris-Pc, two of the three phthalocyanine
branches form a pre-associated face-to-face dimeric conformation with the third
one acting as a monomeric unit; this is consistent with the results of the
transient absorption experiments from the perspective of molecular structure. The
detailed structure-property relationships in phthalocyanine compounds is useful
for exploring the function of molecular aggregates in energy migration of natural
photosynthesis systems.
PMID- 26436830
TI - Strain ZP - the first bacterial conjugation-based "kill"-"anti-kill"
antimicrobial system.
AB - As multidrug resistant bacteria pose one of the greatest risks to human health
new alternative antibacterial agents are urgently needed. One possible mechanism
that can be used as an alternative to traditional antibiotic therapy is transfer
of killing agents via conjugation. Our work was aimed at providing a proof of
principle that conjugation-based antimicrobial systems are possible. We
constructed a bacterial conjugation-based "kill"-"anti-kill" antimicrobial system
employing the well known Escherichia coli probiotic strain Nissle 1917
genetically modified to harbor a conjugative plasmid carrying the "kill" gene
(colicin ColE7 activity gene) and a chromosomally encoded "anti-kill" gene (ColE7
immunity gene). The constructed strain acts as a donor in conjugal transfer and
its efficiency was tested in several types of conjugal assays. Our results
clearly demonstrate that conjugation-based antimicrobial systems can be highly
efficient.
PMID- 26436832
TI - Stable and High-Performance Flexible ZnO Thin-Film Transistors by Atomic Layer
Deposition.
AB - Passivation is a challenging issue for the oxide thin-film transistor (TFT)
technologies because it requires prolonged high-temperature annealing treatments
to remedy defects produced in the process, which greatly limits its
manufacturability as well as its compatibility with temperature-sensitive
materials such as flexible plastic substrates. This study investigates the defect
formation mechanisms incurred by atomic layer deposition (ALD) passivation
processes on ZnO TFTs, based on which we demonstrate for the first time
degradation-free passivation of ZnO TFTs by a TiO2/Al2O3 nanolaminated (TAO) film
deposited by a low-temperature (110 degrees C) ALD process. By combining the TAO
passivation film with ALD dielectric and channel layers into an integrated low
temperature ALD process, we successfully fabricate flexible ZnO TFTs on plastics.
Thanks to the exceptional gas-barrier property of the TAO film (water vapor
transmission rate (WVTR)<10(-6) g m(-2) day(-1)) as well as the defect-free
nature of the ALD dielectric and ZnO channel layers, the TFTs exhibit excellent
device performance with high stability and flexibility: field-effect mobility>20
cm2 V(-1) s(-1), subthreshold swing<0.4 V decade(-1) after extended bias
stressing (>10,000 s), air-storage (>1200 h), and bending (1.3 cm radius for 1000
times).
PMID- 26436831
TI - Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012
2013.
AB - IMPORTANCE: Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly
reported worldwide as a cause of infections with high-mortality rates. Assessment
of the US epidemiology of CRE is needed to inform national prevention efforts.
OBJECTIVE: To determine the population-based CRE incidence and describe the
characteristics and resistance mechanism associated with isolates from 7 US
geographical areas. DESIGN, SETTING, AND PARTICIPANTS: Population- and laboratory
based active surveillance of CRE conducted among individuals living in 1 of 7 US
metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New
York, and Oregon. Cases of CRE were defined as carbapenem-nonsusceptible
(excluding ertapenem) and extended-spectrum cephalosporin-resistant Escherichia
coli, Enterobacter aerogenes, Enterobacter cloacae complex, Klebsiella
pneumoniae, or Klebsiella oxytoca that were recovered from sterile-site or urine
cultures during 2012-2013. Case records were reviewed and molecular typing for
common carbapenemases was performed. EXPOSURES: Demographics, comorbidities,
health care exposures, and culture source and location. MAIN OUTCOMES AND
MEASURES: Population-based CRE incidence, site-specific standardized incidence
ratios (adjusted for age and race), and clinical and microbiological
characteristics. RESULTS: Among 599 CRE cases in 481 individuals, 520 (86.8%; 95%
CI, 84.1%-89.5%) were isolated from urine and 68 (11.4%; 95% CI, 8.8%-13.9%) from
blood. The median age was 66 years (95% CI, 62.1-65.4 years) and 284 (59.0%; 95%
CI, 54.6%-63.5%) were female. The overall annual CRE incidence rate per 100<000
population was 2.93 (95% CI, 2.65-3.23). The CRE standardized incidence ratio was
significantly higher than predicted for the sites in Georgia (1.65 [95% CI, 1.20
2.25]; P < .001), Maryland (1.44 [95% CI, 1.06-1.96]; P = .001), and New York
(1.42 [95% CI, 1.05-1.92]; P = .048), and significantly lower than predicted for
the sites in Colorado (0.53 [95% CI, 0.39-0.71]; P < .001), New Mexico (0.41 [95%
CI, 0.30-0.55]; P = .01), and Oregon (0.28 [95% CI, 0.21-0.38]; P < .001). Most
cases occurred in individuals with prior hospitalizations (399/531 [75.1%; 95%
CI, 71.4%-78.8%]) or indwelling devices (382/525 [72.8%; 95% CI, 68.9%-76.6%]);
180 of 322 (55.9%; 95% CI, 50.0%-60.8%) admitted cases resulted in a discharge to
a long-term care setting. Death occurred in 51 (9.0%; 95% CI, 6.6%-11.4%) cases,
including in 25 of 91 cases (27.5%; 95% CI, 18.1%-36.8%) with CRE isolated from
normally sterile sites. Of 188 isolates tested, 90 (47.9%; 95% CI, 40.6%-55.1%)
produced a carbapenemase. CONCLUSIONS AND RELEVANCE: In this population- and
laboratory-based active surveillance system in 7 states, the incidence of CRE was
2.93 per 100<000 population. Most CRE cases were isolated from a urine source,
and were associated with high prevalence of prior hospitalizations or indwelling
devices, and discharge to long-term care settings.
PMID- 26436833
TI - Photonic Crystal Hydrogel Enhanced Plasmonic Staining for Multiplexed Protein
Analysis.
AB - Plasmonic nanoparticles are commonly used as optical transducers in sensing
applications. The optical signals resulting from the interaction of analytes and
plamsonic nanoparticles are influenced by surrounding physical structures where
the nanoparticles are located. This paper proposes inverse opal photonic crystal
hydrogel as 3D structure to improve Raman signals from plasmonic staining. By
hybridization of the plasmonic nanoparticles and photonic crystal, surface
enhanced Raman spectroscopy (SERS) analysis of multiplexed protein is realized.
It benefits the Raman analysis by providing high-density "hot spots" in 3D and
extra enhancement of local electromagnetic field at the band edge of PhC with
periodic refractive index distribution. The strong interaction of light and the
hybrid 3D nanostructure offers new insights into plasmonic nanoparticle
applications and biosensor design.
PMID- 26436834
TI - Aims and approaches of Web-RADR: a consortium ensuring reliable ADR reporting via
mobile devices and new insights from social media.
AB - INTRODUCTION: Advent of new technologies in mobile devices and software
applications is leading to an evolving change in the extent, geographies and
modes for use of internet. Today, it is used not only for information gathering
but for sharing of experiences, opinions and suggestions. Web-Recognizing Adverse
Drug Reactions (RADR) is a groundbreaking European Union (EU) Innovative
Medicines Innovation funded 3-year initiative to recommend policies, frameworks,
tools and methodologies by leveraging these new developments to get new insights
in drug safety. AREAS COVERED: Data were gathered from prior surveys, previous
initiatives and a review of relevant literature was done. New technologies
provide an opportunity in the way safety information is collected, helping
generate new knowledge for safety profile of drugs as well as unique insights
into the evolving pharmacovigilance system in general. It is critical that these
capabilities are harnessed in a way that is ethical, compliant with regulations,
respecting data privacy and used responsibly. At the same time, the process for
managing and interpreting this new information must be efficient and effective
for sustenance, thoughtful use of resources and valuable return of knowledge.
These approaches should complement the ongoing progress toward personalized
medicine. EXPERT OPINION: This Web-RADR initiative should provide some directions
on 'what and how' to use social media to further proactive pharmacovigilance and
protection of public health. It is expected to also show how a multipronged
expert consortium group comprising regulators, industry and academia can leverage
new developments in technology and society to bring innovation in process,
operations, organization and scientific approaches across its boundaries and
beyond the normal realms of individual research units. These new approaches
should bring insights faster, earlier, specific, actionable and moving toward the
target of AE prevention. The possibilities of a blended targeted
pharmacovigilance (PV) approach where boundaries between stakeholders blur and
cultures mix point to very different future for better, healthier and longer
lives.
PMID- 26436837
TI - Synthesis of Inert Homo- and Heterodinuclear Rare-Earth Cryptates.
AB - A new ditopic cryptand based on two tris(biaryl)-based binding pockets bridged by
a 2,2'-bipyrimidine unit enables the selective synthesis of homo- and
heterodinuclear rare-earth cryptates, which are kinetically inert under
challenging conditions and can even be purified by preparative high-performance
liquid chromatography.
PMID- 26436836
TI - Age Impacts Pulmonary Inflammation and Systemic Bone Response to Inhaled Organic
Dust Exposure.
AB - Agricultural workers have high rates of airway and skeletal health disease.
Studies recently demonstrated that inhaled agricultural organic dust extract
(ODE)-induced airway injury is associated with bone deterioration in an animal
model. However, the effect of age in governing these responses to organic dusts
is unclear, but might be important in future approaches. Young (7-9 wk) and older
(12-14,o) male C57BL/6 mice received intranasal (i.n.) inhalation exposure to ODE
from swine confinement facilities once or daily for 3 wk. Acute ODE-induced
neutrophil influx and cytokine and chemokine (tumor necrosis factor [TNF]-alpha,
interleukin [IL]-6, keratinocyte chemoattractant [CXCL1], macrophage inflammatory
protein-2 [CXCL2]) airway production were reduced in older compared to young
mice. Repetitive ODE treatment, however, increased lymphocyte recruitment and
alveolar compartment histopathologic inflammatory changes in older mice. Whole
lung cell infiltrate analysis revealed that young, but not older, mice
repetitively treated with ODE demonstrated an elevated CD4:CD8 lymphocyte
response. Acute inhalant ODE exposure resulted in a 4-fold and 1.5-fold rise in
blood neutrophils in young and older mice, respectively. Serum IL-6 and CXCL1
levels were elevated in young and older mice i.n. exposed once to ODE, with
increased CXCL1 levels in younger compared to older mice. Although older mice
displayed reduced bone measurements compared to younger mice, younger rodents
demonstrated ODE-induced decrease in bone mineral density, bone volume, and bone
microarchitecture quality as determined by computed tomography (CT) analysis.
Collectively, age impacts the airway injury and systemic inflammatory and bone
loss response to inhalant ODE, suggesting an altered and enhanced immunologic
response in younger as compared to older counterparts.
PMID- 26436835
TI - Effects of developmental exposure to bisphenol A on spatial navigational learning
and memory in rats: A CLARITY-BPA study.
AB - Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of a
wide variety of items. Previous studies suggest BPA exposure may result in neuro
disruptive effects; however, data are inconsistent across animal and human
studies. As part of the Consortium Linking Academic and Regulatory Insights on
BPA Toxicity (CLARITY-BPA), we sought to determine whether female and male rats
developmentally exposed to BPA demonstrated later spatial navigational learning
and memory deficits. Pregnant NCTR Sprague-Dawley rats were orally dosed from
gestational day 6 to parturition, and offspring were directly orally dosed until
weaning (postnatal day 21). Treatment groups included a vehicle control, three
BPA doses (2.5MUg/kg body weight (bw)/day-[2.5], 25MUg/kg bw/day-[25], and
2500MUg/kg bw/day-[2500]) and a 0.5MUg/kg/day ethinyl estradiol (EE)-reference
estrogen dose. At adulthood, 1/sex/litter was tested for seven days in the Barnes
maze. The 2500 BPA group sniffed more incorrect holes on day 7 than those in the
control, 2.5 BPA, and EE groups. The 2500 BPA females were less likely than
control females to locate the escape box in the allotted time (p value=0.04).
Although 2.5 BPA females exhibited a prolonged latency, the effect did not reach
significance (p value=0.06), whereas 2.5 BPA males showed improved latency
compared to control males (p value=0.04), although the significance of this
result is uncertain. No differences in serum testosterone concentration were
detected in any male or female treatment groups. Current findings suggest
developmental exposure of rats to BPA may disrupt aspects of spatial navigational
learning and memory.
PMID- 26436838
TI - Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice.
AB - Cardiac pressure-volume loop analysis is the "gold-standard" in the assessment of
load-dependent and load-independent measures of ventricular systolic and
diastolic function. Measures of ventricular contractility and compliance are
obtained through examination of cardiac response to changes in afterload and
preload. These techniques were originally developed nearly three decades ago to
measure cardiac function in large mammals and humans. The application of these
analyses to small mammals, such as mice, has been accomplished through the
optimization of microsurgical techniques and creation of conductance catheters.
Conductance catheters allow for estimation of the blood pool by exploiting the
relationship between electrical conductance and volume. When properly performed,
these techniques allow for testing of cardiac function in genetic mutant mouse
models or in drug treatment studies. The accuracy and precision of these studies
are dependent on careful attention to the calibration of instruments, systematic
conduct of hemodynamic measurements and data analyses. We will review the methods
of conducting pressure-volume loop experiments using a conductance catheter in
mice.
PMID- 26436841
TI - "Bitten By Shyness": Menstrual Hygiene Management, Sanitation, and the Quest for
Privacy in South Africa.
AB - Little is known about how menstruation is managed in low-income settings and
whether existing sanitation systems meet women's needs. Using the 'Photovoice'
method with 21 women in participatory workshops and in-depth interviews, we
collected data on menstrual hygiene management in three sites in Durban, South
Africa. All women reported using disposable sanitary pads. Although they were
aware that disposable pads were nonbiodegradable, incompatible with waterborne
flush systems, and fill up pit latrines, they had little experience with reusable
products. Considerable energy was devoted to concealing and containing 'menstrual
waste,' and women expressed concern about inadequate privacy during menstruation.
All sites lacked discreet disposal options and reliable water access, while
outdoor sanitation facilities were considered unsafe. Findings highlight the need
for advocacy to improve safety and privacy of facilities for women in this
setting.
PMID- 26436840
TI - Determinants of amyloid fibril degradation by the PDZ protease HTRA1.
AB - Excessive aggregation of proteins has a major impact on cell fate and is a
hallmark of amyloid diseases in humans. To resolve insoluble deposits and to
maintain protein homeostasis, all cells use dedicated protein disaggregation,
protein folding and protein degradation factors. Despite intense recent research,
the underlying mechanisms controlling this key metabolic event are not well
understood. Here, we analyzed how a single factor, the highly conserved serine
protease HTRA1, degrades amyloid fibrils in an ATP-independent manner. This PDZ
protease solubilizes protein fibrils and disintegrates the fibrillar core
structure, allowing productive interaction of aggregated polypeptides with the
active site for rapid degradation. The aggregate burden in a cellular model of
cytoplasmic tau aggregation is thus reduced. Mechanistic aspects of ATP
independent proteolysis and its implications in amyloid diseases are discussed.
PMID- 26436839
TI - New IDH1 mutant inhibitors for treatment of acute myeloid leukemia.
AB - Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are driver mutations in
acute myeloid leukemia (AML) and other cancers. We report the development of new
allosteric inhibitors of mutant IDH1. Crystallographic and biochemical results
demonstrated that compounds of this chemical series bind to an allosteric site
and lock the enzyme in a catalytically inactive conformation, thereby enabling
inhibition of different clinically relevant IDH1 mutants. Treatment of IDH1
mutant primary AML cells uniformly led to a decrease in intracellular 2-HG,
abrogation of the myeloid differentiation block and induction of granulocytic
differentiation at the level of leukemic blasts and more immature stem-like
cells, in vitro and in vivo. Molecularly, treatment with the inhibitors led to a
reversal of the DNA cytosine hypermethylation patterns caused by mutant IDH1 in
the cells of individuals with AML. Our study provides proof of concept for the
molecular and biological activity of novel allosteric inhibitors for targeting
different mutant forms of IDH1 in leukemia.
PMID- 26436842
TI - Spousal similarity in life satisfaction before and after divorce.
AB - Previous research has explored possible origins of individual differences in
subjective well-being, focusing largely on stable, internal characteristics of
traits as predictors of life satisfaction (Diener & Lucas, 1999). Although past
work has demonstrated that life satisfaction is largely stable over the life
span, other evidence has also demonstrated the lasting impact of life events. In
this study, we use married couples as a test of the impact of life circumstances
on life satisfaction, focusing on similarity in life satisfaction before and
after divorce. If life satisfaction is impacted by shared life circumstances,
married couples (who share life circumstances) should show greater similarity in
life satisfaction before divorce than after. We tested this possibility using a
dyadic latent-state-trait model that examined cross-spouse similarity in the
stable and changing components of life satisfaction. Using a nationally
representative panel study from Germany (Wagner, Frick & Schupp, 2007), we showed
that similarity declined substantially following divorce. This suggests that life
satisfaction is related to shared life circumstances.
PMID- 26436843
TI - Do people's world views matter? The why and how.
AB - Over the past decades, personality and social psychologists have extensively
investigated the role of self-views in individual functioning. Research on world
views, however, has been less well studied due to overly specific
conceptualizations, and little research about how and why they impact life
outcomes. To answer why and how world views matter, we conducted 7 studies to
examine the functions, antecedents, and consequences of generalized beliefs about
the world, operationalized as social axioms (Leung et al., 2002). This research
focused on 2 axiom factors, namely, social cynicism and reward for application.
These axioms were found to explain individual differences in self-views over and
above personality traits in Hong Kong and U.S. samples (Study 1) and to explain
cultural differences in self-views in addition to self-construals among Mainland
Chinese, Hong Kong Chinese, East Asian Canadians, and European Canadians (Study
2). Endorsement of social axioms by participants, their parents, and close
friends was collected from Mainland China, Hong Kong, and Canada to infer
parental and peer influences on world views (Study 3). World views affected
psychological well-being through the mediation of positive self-views across 3
age groups, including children, adolescents, and young adults (Study 4) and over
time (Study 5). The mediation of negative self-views was through comparative self
criticism rather than internalized self-criticism (Study 6). Holistic thinking
moderated the effect of social cynicism on self-views and psychological well
being (Study 7). These results converge to show that world views as a distal
force and self-views as a proximal force matter in people's subjective evaluation
of their lives. (PsycINFO Database Record
PMID- 26436844
TI - Comparative evaluation of Bis(thiosemicarbazone)- Biotin and Met-ac-TE3A for
tumor imaging.
AB - 2,2',2"-(11-(2-((4-mercapto-1-methoxy-1-oxobutan-2-yl)amino)-2-oxoethyl)-1,4,8,11
tetraaza cyclotetradecane-1,4,8-triyl)triacetic acid, Met-ac-TE3A and (E)-N
methyl-2-((E)-3-(2-(2-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4
yl)pentanoyl)hydrazinecarbono-thioyl)hydrazonobutan-2
ylidene)hydrazinecarbothioamide, Bis(thiosemicarbazone)- Biotin were synthesized
and evaluated for imaging application. The pharmacokinetics of these ligands were
determined by tracer methods. In vitro human serum stability of (99m)Tc Met-ac
TE3A/(99m)Tc Bis(thiosemicarbazone)-Biotin after 24h was found to be 96.5% and
97.0% respectively. Blood kinetics of both ligands in normal rabbits showed
biphasic clearance pattern. Ex vivo biodistribution study revealed significant
initial tumor uptake and high tumor/muscles ratio which is a pre-requisite
condition for a ligand to work as SPECT-radiopharmaceutical for tumor imaging.
PMID- 26436845
TI - Modeling techniques and fluorescence imaging investigation of the interactions of
an anthraquinone derivative with HSA and ctDNA.
AB - A new anthraquinone derivative (AORha) was synthesized. Its interactions with
human serum albumin (HSA) and calf thymus DNA (ctDNA) were investigated by
fluorescence spectroscopy, UV-visible absorption spectroscopy and molecular
modeling. Cell viability assay and cell imaging experiment were performed using
cervical cancer cells (HepG2 cells). The fluorescence results revealed that the
quenching mechanism was static quenching. At different temperatures (290, 300,
310 K), the binding constants (K) and the number of binding sites (n) were
determined, respectively. The positive DeltaH and DeltaS values showed that the
binding of AORha with HSA was hydrophobic force, which was identical with the
molecular docking result. Studying the fluorescence spectra, UV spectra and
molecular modeling also verified that the binding mode of AORha and ctDNA might
be intercalative. When HepG2 cells were treated with AORha, the fluorescence
became brighter and turned green, which could be used for bioimaging.
PMID- 26436846
TI - Spectroscopic investigation on cocrystal formation between adenine and fumaric
acid based on infrared and Raman techniques.
AB - As an important component of double-stranded DNA, adenine has powerful hydrogen
bond capability, due to rich hydrogen bond donors and acceptors existing within
its molecular structure. Therefore, it is easy to form cocrystal between adenine
and other small molecules with intermolecular hydrogen-bond effect. In this work,
cocrystal of adenine and fumaric acid has been characterized as model system by
FT-IR and FT-Raman spectral techniques. The experimental results show that the
cocrystal formed between adenine and fumaric acid possesses unique
spectroscopical characteristic compared with that of starting materials. Density
functional theory (DFT) calculation has been performed to optimize the molecular
structures and simulate vibrational modes of adenine, fumaric acid and the
corresponding cocrystal. Combining the theoretical and experimental vibrational
results, the characteristic bands corresponding to bending and stretching
vibrations of amino and carbonyl groups within cocrystal are shifted into lower
frequencies upon cocrystal formation, and the corresponding bond lengths show
some increase due to the effect of intermolecular hydrogen bonding. Different
vibrational modes shown in the experimental spectra have been assigned based on
the simulation DFT results. The study could provide experimental and theoretical
benchmarks to characterize cocrystal formed between active ingredients and
cocrystal formers and also the intermolecular hydrogen-bond effect within
cocrystal formation process by vibrational spectroscopic techniques.
PMID- 26436847
TI - Discrimination of genetically modified sugar beets based on terahertz
spectroscopy.
AB - The objective of this paper was to apply terahertz (THz) spectroscopy combined
with chemometrics techniques for discrimination of genetically modified (GM) and
non-GM sugar beets. In this paper, the THz spectra of 84 sugar beet samples (36
GM sugar beets and 48 non-GM ones) were obtained by using terahertz time-domain
spectroscopy (THz-TDS) system in the frequency range from 0.2 to 1.2 THz. Three
chemometrics methods, principal component analysis (PCA), discriminant analysis
(DA) and discriminant partial least squares (DPLS), were employed to classify
sugar beet samples into two groups: genetically modified organisms (GMOs) and non
GMOs. The DPLS method yielded the best classification result, and the percentages
of successful classification for GM and non-GM sugar beets were both 100%.
Results of the present study demonstrate the usefulness of THz spectroscopy
together with chemometrics methods as a powerful tool to distinguish GM and non
GM sugar beets.
PMID- 26436848
TI - Can statistical linkage of missing variables reduce bias in treatment effect
estimates in comparative effectiveness research studies?
AB - AIM: Missing data, particularly missing variables, can create serious analytic
challenges in observational comparative effectiveness research studies.
Statistical linkage of datasets is a potential method for incorporating missing
variables. Prior studies have focused upon the bias introduced by imperfect
linkage. METHODS: This analysis uses a case study of hepatitis C patients to
estimate the net effect of statistical linkage on bias, also accounting for the
potential reduction in missing variable bias. RESULTS: The results show that
statistical linkage can reduce bias while also enabling parameter estimates to be
obtained for the formerly missing variables. CONCLUSION: The usefulness of
statistical linkage will vary depending upon the strength of the correlations of
the missing variables with the treatment variable, as well as the outcome
variable of interest.
PMID- 26436849
TI - Association Study of Matrix Metalloproteinases Gene Polymorphisms with
Susceptibility to Rheumatoid Arthritis: A Meta-Analysis.
AB - OBJECTIVE: Association of matrix metalloproteinases (MMPs) gene polymorphisms
with rheumatoid arthritis is controversial. We conduct a meta-analysis to clarify
this dispute. METHODS: We systematically searched the electronic PUBMED, EMBASE
and CNKI databases for research articles about MMPs (MMP-1, MMP-2, MMP-3, MMP-9)
gene polymorphisms and rheumatoid arthritis (RA) up to January 2015. According to
the heterogeneity, fixed-effects or random-effects models were used to calculate
crude odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total
of 11 articles involving 2143 cases and 2049 controls were included in this meta
analysis. Overall, no significant associations were observed between MMP-1-1607
1G/2G polymorphism and RA. Stratification by ethnicity, no significant
associations were observed in Caucasian populations. Similarly, no significant
associations were observed between MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms
and RA in overall and Caucasian populations, respectively. However, a weak
association was found between MMP-2-1306 C/T polymorphism and RA (C vs. T, OR =
0.813, 95%CI = 0.694-0.953, p = 0.010) in overall populations. CONCLUSIONS: The
present meta-analysis suggests that MMP-1-1607 1G/2G, MMP-3-1171 5A/6A, MMP-9
1562 C/T polymorphisms are not associated with the susceptibility of RA, but MMP
2 -1306 C/T is weakly associated with susceptibility to RA. Further studies with
more sample size are needed for definitive conclusions.
PMID- 26436850
TI - Relation of interleukin-10 Promoter Polymorphisms to Adult Chronic Immune
Thrombocytopenic Purpura in a Cohort of Egyptian Population.
AB - BACKGROUND: Adult chronic immune thrombocytopenic purpura (chronic ITP) is an
autoimmune multifactorial bleeding disorder that occurs because of enhanced
peripheral platelet destruction. Treatment decisions can be challenging because
the goal of treatment is to prevent severe bleeding, but the risk of bleeding can
be difficult to estimate for any individual patient. OBJECTIVE: This case-control
study was planned to investigate the relationship of interleukin (IL)-10 promoter
(IL-10-1082, -819 and -592) polymorphisms with the susceptibility, severity and
outcome of adult chronic ITP in a cohort of Egyptian population. SUBJECTS AND
METHODS: Typing of IL-10 promoter polymorphisms was done using restriction
fragment length polymorphism for 62 adult patients with chronic ITP and 73 age-
and sex-matched healthy controls. RESULTS: No significant differences were found
between ITP patients and controls regarding the frequency of IL-10 promoter
genotypes, alleles or haplotypes. IL-10-592 AA genotype and ATA (IL-10-1082, -819
and -592) haplotype were associated with severe ITP (p = 0.003, 0.043,
respectively). CONCLUSION: Our findings suggest that the IL-10 promoter
polymorphisms are unlikely to affect the development or treatment outcome of
chronic adult ITP in Egyptian population, but IL-10-592 AA genotype and IL-10 (
1082, -819 and -592) ATA haplotype may be associated with disease severity.
Because ITP is a complex disease, it is recommended that a multicenter study
should be done with large sample size and unified typing technique.
PMID- 26436851
TI - Comparing Antibody Responses in Chickens Against Plasmodium falciparum Lactate
Dehydrogenase and Glyceraldehyde-3-phosphate Dehydrogenase with Freund's and
Pheroid(r) Adjuvants.
AB - Pheroid(r) technology was assessed as an alternative to Freund's adjuvant to
raise antibodies in experimental animals. Chickens were immunized with two
recombinantly expressed Plasmodium falciparum proteins, lactate dehydrogenase
(PfLDH) and glyceraldehyde-3-phosphate dehydrogenase (PfGAPDH), alone or in
combination with Freund's adjuvant or Pheroid(r). Chicken egg yolk antibodies
(IgY) were isolated and compared for specificity, sensitivity and yield. Freund's
adjuvant and Pheroid(r) stimulated prolonged antibody responses in chickens
against both antigens. Affinity purified antibodies had specificity for the
recombinant and the native proteins on Western blots. Antibodies generated in the
presence of Freund's adjuvant had high sensitivity for both antigens. Pheroid(r)
generated antibodies that detected the lowest concentration of recombinant PfLDH.
Freund's adjuvant and Pheroid(r) both improved chicken IgY yields, with
Pheroid(r) showing a 2-fold increase relative to controls. Pheroid(r) was well
tolerated in chickens and has potential for development as a safe adjuvant for
testing alternative stimulatory factors to improve adjuvant formulations.
PMID- 26436852
TI - Circulating CD4(+)CXCR5(+) T Cells Exacerbate B Cell Antibody Production in
Crohn's Disease Through IL-21 Secretion.
AB - Interleukin-21 (IL-21) upregulation was observed in Crohn's disease (CD) patients
and was shown to contribute to ongoing mucosal inflammation in CD patients
through stabilizing Th1 cell differentiation and IFN-gamma production. Given the
role of IL-21 in mediating adaptive B cell antibody responses in healthy
individuals, we examined the effect of IL-21 upregulation in B cell responses in
patients with active CD, including ileum, ileocolonic and colon subtypes, defined
by the primary site of CD involvement. We first observed an upregulation of blood
plasma IL-21 concentration and IL-21 production from CD4(+) T cells in CD
patients compared to healthy individuals. The IL-21-expressing T cells were more
concentrated in the CD4(+)CXCR5(+) compartment, both in unstimulated medium and
after stimulation with SEB. ICOS and PD-1 expressions were also concentrated in
the CD4(+)CXCR5(+) subset in CD patients. Since peripheral blood CD4(+)CXCR5(+) T
cell-mediated antibody secretion is IL-21-dependent, we examined the plasma
antibody concentration in CD patients and healthy controls. We found that CD
patients had significantly higher plasma Ig level than healthy patients, with no
significant differences between different CD subtypes. Higher plasma IL-21
concentration and increased IL-21 production from CD4(+) T cells were directly
correlated with higher plasma antibody levels. Moreover, we found that IL-21 and
CD4(+)CXCR5(+) T cells can directly enhance B cell antibody response in CD
patients. Depletion of secreted IL-21 by sIL-21R addition compromised the
CD4(+)CXCR5(+) T cell-mediated increase in antibody production. Together, our
results demonstrated a novel role of IL-21 in mediating B cell inflammation in CD
development.
PMID- 26436853
TI - Short-Chain Fatty Acids Regulate Secretion of IL-8 from Human Intestinal
Epithelial Cell Lines in vitro.
AB - Short-chain fatty acids (SCFAs) including acetate, propionate and butyrate play
an important role in the physiological functions of epithelial cells and
colonocytes, such as immune response regulation. Human intestinal epithelial
cells (IECs) contribute in intestinal immune response via different ways, such as
production of different immune factors including Interleukin (IL) IL-8, which act
as chemoattractant for neutrophils, and subsequently enhance inflammation.
Therefore, we aimed to evaluate the effects of SCFAs on IECs viability and
production of IL-8 in vitro. SCFAs were co-cultured with either normal intestinal
epithelial (T4056) or adenocarcinoma derived (HT-29) cell lines for 24-96 h in
the presence of E.coli lipopolysaccharides (LPS). Cell viability, proliferation,
production of IL-8 and expression of IL-8 mRNA were determined in the cell
cultures. The result showed that 20 mM of SCFAs was non-cytotoxic to T4056 and
enhanced their growth, whereas the growth of HT-29 was inhibited. The SCFAs down
regulated LPS-stimulated IL-8 secretion with different response patterns, but no
obvious effects on the release of IL-8 from non LPS- stimulated cells. In
conclusion, SCFAs showed regulatory effect on release of LPS-stimulated IL-8 as
well as the expression of mRNA of IL-8; these might explain the anti-inflammatory
and anti-carcinogenic mechanism of SCFAs.
PMID- 26436854
TI - Prophylactic Effect of BIO-1211 Small-Molecule Antagonist of VLA-4 in the EAE
Mouse Model of Multiple Sclerosis.
AB - BACKGROUND AND PURPOSE: Some functional limitations and economic burden of
therapeutic antibodies indicated that introducing of alternative therapeutic
compounds with same or different mechanism of action could be worthwhile. In this
regard small-molecule antagonists can have a wide range of impacts, so in this
research, we examine the prophylactic effects of BIO-1211 [Very Late Antigen-4
(VLA4) blocker], in experimental autoimmune encephalomyelitis (EAE) mouse model
of multiple sclerosis in comparison with commercial available medicine,
Natalizumab (NTZ)]. METHODS: EAE was induced by subcutaneous immunization of
myelin oligodendrocyte glycoprotein (MOG35-55) in 8-week-old C57BL/6 mice. During
EAE induction, mice were separated to distinct groups and provided either BIO
1211 (5 and 10 mg/kg) or NTZ (5 mg/kg) and co-administration of these two
compounds. After 21 days, neuro-inflammatory responses were analyzed using qRT
PCR, western blot, and ELISA methods. Pervade of immune cells to brain was
examined by Evans blue staining and immunohistochemistry (IHC) analysis of
specific markers of microglia/monocytes (CD11b) and leukocytes (CD45). RESULTS:
Targeted disruption of VLA4/VCAM1 interactions, by BIO-1211 agonist in mice,
results in reduced cytokines expression, leukocyte trafficking, and inhibition of
inflammatory responses in EAE (p < 0.01) in a dose-independent manner (data not
shown). Mice treated with both BIO-1211 and NTZ exhibited a considerable
depletion in the EAE clinical score, which correlated with decreased expression
of TNF-alpha, IL-17, IFN-gamma and pervade of CD11b(+) and CD45(+) cells into the
cerebral cortex. CONCLUSION: Our results indicated that BIO12-11 compound would
be an useful tool to further understand the biological roles of VLA4/VCAM1
interactions, and could also be considered as EAE-suppressing agent.
PMID- 26436855
TI - UV-induced DNA Damage: The Role of Electronic Excited States.
AB - The knowledge of the fundamental processes induced by the direct absorption of UV
radiation by DNA allows extrapolating conclusions drawn from in vitro studies to
the in-vivo DNA photoreactivity. In this respect, the characterization of the DNA
electronic excited states plays a key role. For a long time, the mechanisms of
DNA lesion formation were discussed in terms of generic "singlet" and "triplet"
excited state reactivity. However, since the beginning of the 21(st) century,
both experimental and theoretical studies revealed the existence of "collective"
excited states, i.e. excited states delocalized over at least two bases. Two
limiting cases are distinguished: Frenkel excitons (delocalized pipi* states) and
charge-transfer states in which positive and negative charges are located on
different bases. The importance of collective excited states in photon absorption
(in particular in the UVA spectral domain), the redistribution of the excitation
energy within DNA, and the formation of dimeric pyrimidine photoproducts is
discussed. The dependence of the behavior of the collective excited states on
conformational motions of the nucleic acids is highlighted.
PMID- 26436856
TI - Reactions of superoxide dismutases with HS(-)/H2S and superoxide radical anion:
An in vitro EPR study.
AB - Interactions of hydrogen sulfide (HS(-)/H2S), a reducing signaling species, with
superoxide dimutases (SOD) are poorly understood. We applied low-T EPR
spectroscopy to examine the effects of HS(-)/H2S and superoxide radical anion O2.
on metallocenters of FeSOD, MnSOD, and CuZnSOD. HS(-)/H2S did not affect FeSOD,
whereas active centers of MnSOD and CuZnSOD were open to this agent. Cu(2+) was
reduced to Cu(1+), while manganese appears to be released from MnSOD active
center. Untreated and O2.- treated FeSOD and MnSOD predominantly show 5 d
electron systems, i.e. Fe(3+) and Mn(2+). Our study provides new details on the
mechanisms of (patho)physiological effects of HS(-)/H2S.
PMID- 26436857
TI - Coronary blood flow in the anesthetized American alligator (Alligator
mississippiensis).
AB - Coronary circulation of the heart evolved early within ectothermic vertebrates
and became of vital importance to cardiac performance in some teleost fish,
mammals and birds. In contrast, the role and function of the coronary circulation
in ectothermic reptiles remains largely unknown. Here, we investigated the
systemic and coronary arterial responses of five anesthetized juvenile American
alligators (Alligator mississippiensis) to hypoxia, acetylcholine, adenosine,
sodium nitroprusside, isoproterenol, and phenylephrine. We recorded
electrocardiograms, monitored systemic blood pressure, blood flows in both
aortae, and blood flow in a major coronary artery supplying most of the right
ventricle. Coronary arterial blood flow was generally forward, but there was a
brief retrograde flow during a ventricular contraction. Blood pressure was
significantly changed in all conditions. Acetylcholine decreased coronary forward
flow, but this response was confounded by the concomitant lowered work of the
ventricles due to decreased heart rate and blood pressure. Coronary forward flow
was poorly correlated with heart rate and mean arterial pressure across
treatments. Overall changes in coronary forward flow, significant and not
significant, were generally in the same direction as mean arterial pressure and
ventricular power, approximated as the product of systemic cardiac output and
mean arterial pressure.
PMID- 26436858
TI - In vivo biomechanical properties of heavy versus light weight monofilament
polypropylene meshes. Does the knitting pattern matter?
AB - AIMS: This work evaluated the post-implant biomechanical properties of light
weight (LW) and heavy-weight (HW) monofilament polypropylene (PP) meshes with
different knitting patterns in an animal model in vivo. METHODS: Forty-five adult
female Wistar rats were divided into three groups and randomly implanted with 32
* 32 mm HW-PP (62 gm-2 ) orLW-PP (16 gm-2 ) in the lower abdomen. LW-PPwas tested
orthogonally (called LWL and LWT) to reproduce the longitudinal and transverse
planes of the vaginal wall, respectively. Abdominal walls were removed at 7, 30,
and 60 days, and then tested for tensile load (maximum load until avulsion from
the tissue), deflection, and stiffness to maximum load. Explants were compared
over time and between groups. RESULTS: LW-PP meshes implanted in the LWT fashion
(vaginal transverse plane) showed comparable maximum load and stiffness to HW-PP
meshes, and LW-PP meshes implanted in the LWL fashion (vaginal longitudinal
plane) presented lower maximum load and stiffness than the HW-PP meshes. There
were no significant differences in the values of deflection at maximum load
between the studied meshes as a function of time. CONCLUSIONS: The final
mechanical behavior of PP mesh can be changed by its weight and knitting pattern.
These properties may be useful in making more biocompatible prostheses for pelvic
organ prolapse (POP) with less foreign material to maintain longitudinal vaginal
elasticity and minimize sexual symptoms while maintaining transverse resistance
(i.e., between vaginal fornixes) to prevent POP recurrence. Neurourol. Urodynam.
36:73-79, 2017. (c) 2015 Wiley Periodicals, Inc.
PMID- 26436859
TI - WITHDRAWN: Drugs for preventing malaria in travellers.
PMID- 26436860
TI - Evaluation of Quantitative PET/MR Enterography Biomarkers for Discrimination of
Inflammatory Strictures from Fibrotic Strictures in Crohn Disease.
AB - PURPOSE: To retrospectively evaluate positron emission tomography (PET)/magnetic
resonance (MR) enterography for the differentiation of fibrotic strictures from
inflammatory strictures in patients with Crohn disease. MATERIALS AND METHODS:
This HIPAA-compliant retrospective study was approved by the institutional review
board. Patients gave their written informed consent for study enrollment. PET/MR
enterography images were evaluated in 19 patients with Crohn disease who had
strictures that underwent surgical resection with pathologic confirmation. Two
radiologists and a nuclear medicine physician in consensus evaluated the
following bowel wall PET/MR enterography biomarkers: signal intensity (SI) on T2
weighted images, apparent diffusion coefficient (ADC), PET maximum standardized
uptake value (SUVmax), SI on T2-weighted images * SUVmax, and ADC * SUVmax values
at levels that corresponded to pathologic specimens. MR, PET, and hybrid PET/MR
biomarkers were compared, and the performance for differentiation of inflammatory
strictures from fibrotic strictures was assessed. Mixed-model regression analysis
was used to compare the mean imaging parameters between groups; the P values were
corrected for the five comparisons by using the Bonferroni method. RESULTS: Three
of the PET/MR enterography biomarkers, SUVmax, SI on T2-weighted images * SUVmax,
and ADC * SUVmax, showed significant differences in the fibrosis group compared
with the fibrosis with active inflammation group and the active inflammation only
group. The best discriminator between fibrosis and active inflammation was the
combined PET/MR enterography biomarker ADC * SUVmax cutoff of less than 3000,
which was associated with accuracy, sensitivity, and specificity values of 0.71,
0.67, and 0.73, respectively. CONCLUSION: PET/MR enterography offers a potential
noninvasive technique for the differentiation of purely fibrotic strictures from
mixed or inflammatory strictures. A hybrid biomarker that incorporates both MR
and PET information performed better for stricture evaluation than either
modality alone.
PMID- 26436861
TI - Asymptomatic Progressive Multifocal Leukoencephalopathy Associated with
Natalizumab: Diagnostic Precision with MR Imaging.
AB - PURPOSE: To determine diagnostic precision with magnetic resonance (MR) imaging
of the brain, the most predictive MR imaging features, and the added value of
comparison with previous data for the diagnosis of asymptomatic progressive
multifocal leukoencephalopathy (PML) associated with natalizumab (NTZ). MATERIALS
AND METHODS: This retrospective study was approved by the institutional review
board, and written informed consent was obtained. Eleven consecutive patients
with multiple sclerosis (MS) who had received a definitive diagnosis of
asymptomatic NTZ-associated PML (NTZ PML, 18 brain lesions) underwent 3-T MR
imaging. The control group included 40 patients with MS but without PML who were
treated with NTZ. Three readers independently performed blinded analysis of MR
images. First, the readers were asked to detect NTZ PML lesions without comparing
current images with previously obtained MR imaging data by evaluating MR images
for the following features: U fiber and/or cortex involvement, lesion signal
intensity and borders, and occurrence of punctate lesions. Second, they
reassessed NTZ PML lesions with all the previous MR imaging data available.
Diagnostic precision with MR imaging was assessed with and without comparison
with previously obtained data. Logistic regression analyses were performed to
identify the association of MR imaging features with NTZ PML. RESULTS: Overall
interobserver agreement was good (kappa = 0.76; 95% confidence interval [CI]:
0.71, 0.81). Hyperintensity on diffusion-weighted images and involvement of U
fibers were the most predictive features (odds ratio, 33.7; 95% CI: 4.9, 229.7 [P
< .0001] and odds ratio, 8.7; 95% CI: 1.2, 61.4 [P = .03], respectively), while
punctate lesions were exclusively observed in patients with NTZ PML. Comparison
with previous MR imaging data improved specificity of MR imaging for the
detection of NTZ PML lesions (from 88% to 100%, P = .05). CONCLUSION: Recognition
of the most predictive imaging features and comparison with previous MR imaging
data may facilitate the detection of asymptomatic NTZ PML.
PMID- 26436862
TI - Human Norovirus prevalence in Africa: a review of studies from 1990 to 2013.
AB - OBJECTIVES: To assess the contribution of Human Norovirus to diarrhoeal diseases
in Africa. METHODS: We conducted a systematic review of the PubMed and EMBASE
databases for published articles of Human Norovirus in Africa between 1990 and
2013. Data were extracted from selected studies and analysed. RESULTS: A total of
208 eligible studies were identified, of which 55 (from 19 countries) met the
inclusion criteria. Many cases were of sporadic gastroenteritis (70.9%) in
children (82%), 65.4% of which were seen in an outpatient setting. Over half
(59.4%) of the affected children were under 5 years of age. The pooled prevalence
rate of Human NoV was 11% (95% CI 8-14%), and the meta-analysis indicated
significant heterogeneity between the studies. However, the conditional negative
binomial regression could not clearly find the factors affecting the Human NoV
prevalence rates reported. A close relationship was found between Human Norovirus
strains from environmental and clinical samples. CONCLUSION: Unreported sporadic
gastroenteritis cases of Human Norovirus are common in Africa. Most are community
associated infections. Possible environmental transmission routes have been
documented. Combined environmental and clinical studies are required for targeted
actions to control transmission of Human Norovirus in Africa. Systematic
surveillance of Human Norovirus is needed to measure the burden of Norovirus
induced gastroenteritis in Africa and support any requirements for vaccine
development.
PMID- 26436863
TI - Dismantling Limb-Girdle Muscular Dystrophy: The Role of Whole-Exome Sequencing.
PMID- 26436864
TI - Uncertainty and Possible Subclinical Valve Leaflet Thrombosis.
PMID- 26436866
TI - Stuttering Associated With the Use of Short-Acting Oral Methylphenidate.
PMID- 26436865
TI - Distinct modulation of allergic T cell responses by subcutaneous vs. sublingual
allergen-specific immunotherapy.
AB - BACKGROUND: Allergen-specific immunotherapy is the only curative treatment for
type I allergy. It can be administered subcutaneously (SCIT) or sublingually
(SLIT). The clinical efficacy of these two treatment modalities appears to be
similar, but potential differences in the immunological mechanisms involved have
not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T
cell response induced by subcutaneous vs. sublingual administration of allergen
specific immunotherapy (AIT). METHODS: Grass pollen-allergic patients were
randomized into groups receiving either SCIT injections or SLIT tablets or
neither. PBMCs were tested for Timothy grass (TG)-specific cytokine production by
ELISPOT after in vitro expansion with TG-peptide pools. Phenotypic
characterization of cytokine-producing cells was performed by FACS. RESULTS: In
the SCIT group, decreased IL-5 production was observed starting 10 months after
treatment commenced. At 24 months, T cell responses showed IL-5 levels
significantly below the before-treatment baseline. No significant reduction of IL
5 was observed in the SLIT or untreated group. However, a significant transient
increase in IL-10 production after 10 months of treatment compared to baseline
was detected in both treatment groups. FACS analysis revealed that IL-10
production was associated with CD4(+) T cells that also produced IFNgamma and
therefore may be associated with an IL-10-secreting type 1 cell phenotype.
CONCLUSION AND CLINICAL RELEVANCE: The most dominant immunological changes on a
cellular level were a decrease in IL-5 in the SCIT group and a significant,
transient increase of IL-10 observed after 10 months of treatment in both treated
groups. The distinct routes of AIT administration may induce different
immunomodulatory mechanisms at the cellular level.
PMID- 26436867
TI - Surfactant-free green synthesis of Fe3O4 nanoparticles capped with 3,4
dihydroxyphenethylcarbamodithioate: stable recyclable magnetic nanoparticles for
the rapid and efficient removal of Hg(II) ions from water.
AB - Mercury is considered one of the most notorious global pollutants due to its high
toxicity and widespread use in industry. Although many materials have been
developed for the removal of mercury for water purification, most of these
materials are difficult to reuse, which may lead to an increase in the mercury
handling expense. Therefore, new sustainable materials that can be easily
recycled and are highly efficient for the removal of mercury are required.
Herein, we report the surfactant-free green synthesis of Fe3O4 magnetic
nanoparticles (MNPs) using a watermelon (Citrullus lanatus) rind extract. The
Fe3O4 MNPs were further functionalized with 3,4
dihydroxyphenethylcarbamodithioate (DHPCT) and applied to the removal of Hg(ii).
Evaluation of the mercury removal efficiency and the amount adsorbed by
DHPCT@Fe3O4 MNPs demonstrated a high Hg(ii) removal efficiency (98%) with a
maximum Hg(ii) adsorption capacity of 52.1 mg g(-1). Systematic studies of the
adsorption mechanism and selectivity suggest that the soft ligand (DHPCT) can
preferentially coordinate with the soft metal ion (Hg(ii)) resulting in selective
mercury removal. The developed DHPCT@Fe3O4 MNPs were readily recycled several
times using an external magnet by exploiting their ferromagnetic character,
without a significant decline in the Hg(ii) removal efficiency. This study
provides a new insight into the preparation of a highly efficient adsorbent for
Hg(ii) removal by an eco-friendly method.
PMID- 26436868
TI - Developmental trajectories of form perception: A story of attention.
AB - The developmental trajectories of selective and divided attention were examined
in relation to the processing of hierarchically integrated stimuli. The
participants included children in 4 age groups (6, 8, 10, and 12 years) and a
group of young adults (24 years) who completed 2 computer-based attention tasks.
In the selective attention task, the participants were instructed to attend to
only 1 level of analysis and ignore the other. In the divided attention task,
participants were told that the target could appear at either level, and the
probability that a target would appear at either the global or local level was
manipulated. For both of the tasks, distinct and qualitative developmental shifts
were evident both between 6 and 8 years of age and between 8 and 10 years of age.
Attention to the global form developed prior to, and may have been a prerequisite
of, attention to the local form. These gains in attentional control occurred in
terms of selective attention, sensitivity to the probability of bias, and
relative efficiency in processing global and local targets. The clear
developmental trajectory is consistent with the emergent role of voluntary
attention in the processing of these types of stimuli.
PMID- 26436869
TI - The magic shrinking machine revisited: The presence of props at recall
facilitates memory in 3-year-olds.
AB - In a seminal study Simcock and Hayne (2002) showed that 3-year-olds were unable
to use newly acquired words to describe a "magic" event experienced 6 or 12
months earlier. In the reference study the children's verbal recall was tested
without props being present. Inspired by recent evidence, the original design was
replicated, testing 33-and 39-month-olds (n = 180), but with props present at
recall while controlling for potential online reasoning. The results revealed
that the children did use newly acquired words to describe their preverbal
memory. Thus, the present study shows that nonverbal memories can be verbalized
if the recall setting provides a high level of contextual support, a finding
relevant to researchers investigating the offset of childhood amnesia.
PMID- 26436871
TI - The nonlinear relations of the approximate number system and mathematical
language to early mathematics development.
AB - Both mathematical language and the approximate number system (ANS) have been
identified as strong predictors of early mathematics performance. Yet, these
relations may be different depending on a child's developmental level. The
purpose of this study was to evaluate the relations between these domains across
different levels of ability. Participants included 114 children who were assessed
in the fall and spring of preschool on a battery of academic and cognitive tasks.
Children were 3.12 to 5.26 years old (M = 4.18, SD = .58) and 53.6% were girls.
Both mixed-effect and quantile regressions were conducted. The mixed-effect
regressions indicated that mathematical language, but not the ANS, nor other
cognitive domains, predicted mathematics performance. However, the quantile
regression analyses revealed a more nuanced relation among domains. Specifically,
it was found that mathematical language and the ANS predicted mathematical
performance at different points on the ability continuum. These dual nonlinear
relations indicate that different mechanisms may enhance mathematical acquisition
dependent on children's developmental abilities.
PMID- 26436870
TI - Does school mobility place elementary school children at risk for lower math
achievement? The mediating role of cognitive dysregulation.
AB - Children growing up in poverty have a higher likelihood of exposure to multiple
forms of adversity that jeopardize their chances of academic success. The current
paper identifies school mobility, or changing schools, as 1 such poverty-related
risk. Using a sample of low-income, predominantly ethnic-minority children (n =
381) in Chicago, this study tests the hypothesis that repeatedly changing schools
during the 5-year period between Head Start (preschool) and third grade is a
potent predictor of children's math achievement in fourth grade and that
children's cognitive dysregulation serves as a mechanism through which school
mobility may negatively affect children's math achievement. Hierarchical linear
models controlling for baseline child and family characteristics (including
children's early math and dysregulation measured during Head Start) revealed an
inverse relation between the number of times low-income children changed schools
between preschool and third grade and children's math achievement on state
standardized tests in fourth grade. Furthermore, frequently changing schools (3
or 4 school changes over the same time period) was positively associated with
teacher-reported cognitive dysregulation in third grade and negatively associated
with children's math achievement in fourth grade. Evidence for the role of
children's cognitive dysregulation as a partial statistical mediator was found
for the relation between frequently changing schools and math achievement, even
after accounting for baseline risk. Results are discussed in terms of school
policies, practices, and intervention strategies to prevent the disruptive and
potentially stressful experiences of school mobility for young, low-income
children.
PMID- 26436872
TI - Visuomotor integration and inhibitory control compensate for each other in school
readiness.
AB - Visuomotor integration (VMI), or the ability to copy designs, and 2 measures of
executive function were examined in a predominantly low-income, typically
developing sample of children (n = 467, mean age 4.2 years) from 5 U.S. states.
In regression models controlling for age and demographic variables, we tested the
interaction between visuomotor integration (design copying) and inhibitory
control (pencil-tap) or verbal working memory (digit span) on 4 directly assessed
academic skills and teacher-reported approaches to learning. Compared with
children with both poor visuomotor integration and low inhibitory control, those
on the higher end of the continuum in at least 1 of these 2 skills performed
better across several dependent variables. This compensatory pattern was evident
for longitudinal improvement in print knowledge on the Test of Preschool Early
Literacy (TOPEL), with similar though marginally significant findings for
improvement in phonological awareness (TOPEL) and teacher-rated approaches to
learning on the Preschool Learning Behaviors Scale (PLBS). Of note, the same
compensatory pattern emerged for concurrently measured receptive vocabulary on
the Peabody Picture Vocabulary Test (PPVT), expressive vocabulary on the Woodcock
Johnson III (WJ), TOPEL phonological awareness, and teacher-rated approaches to
learning. The consistent pattern of results suggests that strong visuomotor
integration skills are an important part of school readiness, and merit further
study.
PMID- 26436873
TI - De Novo Biosynthesis of beta-Valienamine in Engineered Streptomyces hygroscopicus
5008.
AB - The C7N aminocyclitol beta-valienamine is a lead compound for the development of
new biologically active beta-glycosidase inhibitors as chemical chaperone
therapeutic agents for lysosomal storage diseases. Its chemical synthesis is
challenging due to the presence of multichiral centers in the structure. Herein,
we took advantage of a heterogeneous aminotransferase with stereospecificity and
designed a novel pathway for producing beta-valienamine in Streptomyces
hygroscopicus 5008, a validamycin producer. The aminotransferase BtrR from
Bacillus circulans was able to convert valienone to beta-valienamine with an
optical purity of up to >99.9% enantiomeric excess value in vitro. When the
aminotransferase gene was introduced into a mutant of S. hygroscopicus 5008
accumulating valienone, 20 mg/L of beta-valienamine was produced after 96 h
cultivation in shaking flasks. This work provides a powerful alternative for
preparing the chiral intermediates for pharmaceutical development.
PMID- 26436874
TI - The Prognostic Significance of Right Bundle Branch Block: A Meta-analysis of
Prospective Cohort Studies.
AB - BACKGROUND: The prognostic significance of right bundle branch block (RBBB) is
inconsistent across studies. We aimed to assess the association between RBBB (in
general population and patients with heart disease) and risk of all-cause
mortality, cardiac death, acute myocardial infarction (MI), and heart failure
(HF). HYPOTHESIS: RBBB may be associated with increased risk of death. METHODS:
PubMed, EMBASE, and the Cochrane Library up to February 2015 were searched for
prospective cohort studies that reported RBBB at baseline and all-cause
mortality, cardiac death, MI, and HF at follow-up. A meta-analysis of published
data was undertaken primarily by means of fixed-effects models. RESULTS: Nineteen
cohort studies including 201 437 participants were included with a mean follow-up
period ranging from 1 to 246 months. For general population with RBBB, the pooled
adjusted hazard ratio (HR) for all-cause mortality was 1.17 (95% confidence
interval [CI]: 1.03-1.33) compared with no BBB. General population with RBBB had
an increased risk of cardiac death (HR: 1.43, 95% CI: 1.17-1.74). For patients
with RBBB and acute MI, the pooled risk ratio was 2.31 (95% CI: 2.13-2.49) for in
hospital mortality, 2.85 (95% CI: 2.46-3.30) for 30-day mortality, and 1.96 (95%
CI: 1.59-2.42) for longer-term mortality. For acute HF patients, the pooled risk
ratio of all-cause mortality was 1.11 (95% CI: 1.06-1.16), and for chronic HF
patients it was 1.75 (95% CI: 1.38-2.22). CONCLUSIONS: Right bundle branch block
is associated with an increased risk of mortality in general population and
patients with heart disease.
PMID- 26436875
TI - Copy number increase of oncoprotein CIP2A is associated with poor patient
survival in human head and neck squamous cell carcinoma.
AB - BACKGROUND: CIP2A, an inhibitor of PP2A tumour suppressor function, is a widely
overexpressed biomarker of aggressive disease and poor therapy response in
multiple human cancer types. METHODS: CIP2A and DPPA4 copy number alterations and
expression were analysed by fluorescence in situ hybridisation (FISH) and
immunohistochemistry (IHC) in different cell lines and a tissue microarray of 52
HNSCC patients. Results were correlated with patient survival and other
clinicopathological data. RESULTS: CIP2A and DPPA4 copy number increase occurred
at a relatively high frequency in human HNSCC patient samples. CIP2A but not
DPPA4 FISH status was significantly associated with patient survival. CIP2A
detection by combining IHC with FISH yielded superior resolution in the
prognostication of HNSCC. CONCLUSIONS: CIP2A copy number increase is associated
with poor patient survival in human HNSCC. We suggest that the reliability and
prognostic value of CIP2A detection can be improved by performing FISH analysis
to CIP2A IHC positive tumours.
PMID- 26436876
TI - The role of pectoralis major flap in reducing the incidence of pharyngocutaneous
fistula following total laryngectomy: a single-centre experience with 102
patients.
PMID- 26436877
TI - Viability of Bioprinted Cellular Constructs Using a Three Dispenser Cartesian
Printer.
AB - Tissue engineering has centralized its focus on the construction of replacements
for non-functional or damaged tissue. The utilization of three-dimensional
bioprinting in tissue engineering has generated new methods for the printing of
cells and matrix to fabricate biomimetic tissue constructs. The solid freeform
fabrication (SFF) method developed for three-dimensional bioprinting uses an
additive manufacturing approach by depositing droplets of cells and hydrogels in
a layer-by-layer fashion. Bioprinting fabrication is dependent on the specific
placement of biological materials into three-dimensional architectures, and the
printed constructs should closely mimic the complex organization of cells and
extracellular matrices in native tissue. This paper highlights the use of the
Palmetto Printer, a Cartesian bioprinter, as well as the process of producing
spatially organized, viable constructs while simultaneously allowing control of
environmental factors. This methodology utilizes computer-aided design and
computer-aided manufacturing to produce these specific and complex geometries.
Finally, this approach allows for the reproducible production of fabricated
constructs optimized by controllable printing parameters.
PMID- 26436879
TI - Co(OH)2 @PANI Hybrid Nanosheets with 3D Networks as High-Performance
Electrocatalysts for Hydrogen Evolution Reaction.
AB - Hybrid electrocatalysts with excellent electrocatalytic activity for hydrogen
reduction are fabricated using an efficient and facile electrochemical route. The
electronic and synergistic effects between Co(OH)2 and polyaniline (PANI) in the
composite structure are the key factors that generate the high electrocatalytic
activity and excellent stability. A highly efficient, non-precious metal-based
flexible electrocatalyst for high-performance electrocatalysts is shown, which
reveals a novel route for the design and synthesis of electrocatalysts.
PMID- 26436880
TI - Metabolic Capacity of Mitochondrion-related Organelles in the Free-living
Anaerobic Stramenopile Cantina marsupialis.
AB - Functionally and morphologically degenerate mitochondria, so-called mitochondrion
related organelles (MROs), are frequently found in eukaryotes inhabiting hypoxic
or anoxic environments. In the last decade, MROs have been discovered from a
phylogenetically broad range of eukaryotic lineages and these organelles have
been revealed to possess diverse metabolic capacities. In this study, the
biochemical characteristics of an MRO in the free-living anaerobic protist
Cantina marsupialis, which represents an independent lineage in stramenopiles,
were inferred based on RNA-seq data. We found transcripts for proteins known to
function in one form of MROs, the hydrogenosome, such as pyruvate:ferredoxin
oxidoreductase, iron-hydrogenase, acetate:succinate CoA-transferase, and succinyl
CoA synthase, along with transcripts for acetyl-CoA synthetase (ADP-forming).
These proteins possess putative mitochondrial targeting signals at their N
termini, suggesting dual ATP generation systems through anaerobic pyruvate
metabolism in Cantina MROs. In addition, MROs in Cantina were also shown to share
several features with canonical mitochondria, including amino acid metabolism and
an "incomplete" tricarboxylic acid cycle. Transcripts for all four subunits of
complex II (CII) of the electron transport chain were detected, while there was
no evidence for the presence of complexes I, III, IV, or F1Fo ATPase. Cantina MRO
biochemistry challenges the categories of mitochondrial organelles recently
proposed.
PMID- 26436881
TI - Dr. Ninan T. Mathew--A "Tribute" (1937-2015).
PMID- 26436882
TI - Understanding contextual influences of community reintegration among injured
servicemembers.
AB - As part of a larger mixed-methods research project investigating the influence of
contextual factors on community reintegration (CR), this qualitative study sought
to understand the subjective experiences of injured servicemembers and their
perception of how contextual factors influenced their CR. More specifically, this
article addresses how the influences of contextual factors differ between injured
servicemembers with different levels of CR. Using a phenomenological framework,
semistructured interviews were conducted with nine injured, community-dwelling
servicemembers with low, moderate, and high levels of CR (three per category).
Participants provided in-depth descriptions of the contextual barriers and
facilitators of CR. Thematic analysis indicated the importance of social support
and personal factors (e.g., self-efficacy, personal motivation) as the primary
means for being reintegrated into their homes and communities. Other themes
indicated factors that had an indirect but important influence on CR, including
adapted sports, recreation, and other social programs; rehabilitation programs
and therapists; school, work, and volunteering; and organizations and policies in
developing social supports and personal factors. Comparisons between
servicemembers indicated participants with low CR described many more contextual
barriers and far fewer contextual facilitators to reintegration than those with
high CR. Those with moderate CR were unique in that they described many
facilitators and barriers to reintegration.
PMID- 26436884
TI - Influence of the Retinal Blood Vessel Topography on the Variability of the
Retinal Nerve Fiber Bundle Trajectories in the Human Retina.
AB - PURPOSE: To determine the relationship between the retinal blood vessel
topography and the retinal nerve fiber bundle (RNFB) trajectories in the human
retina. METHODS: A previously collected dataset comprising 28 fundus photographs
with traced RNFB trajectories was used. For all traced trajectories, the
departure from our previously published RNFB trajectory model was calculated.
Subsequently, we calculated, per subject, a "mean departure" for the superior
temporal and inferior-temporal region. We measured angles between a line
connecting the optic nerve head (ONH) center and the fovea and lines connecting
the ONH center and the crossings of the superior and inferior temporal arteries
(arterial angles) and veins (venous angles) with circles around the ONH; circle
radii were 25%, 50%, and 100% of the ONH center-to-fovea distance. We also
defined two angles based on the location of the first arteriovenous crossing.
Multiple linear regression analysis was performed with mean departure as
dependent variable and refraction, ONH inclination, and vessel angles as
independent variables. RESULTS: In the superior-temporal region, refraction (P =
0.017), ONH inclination (P = 0.021), and the arterial angle corresponding to the
middle circle (P < 0.001) were significant determinants of mean departure.
Explained variance was 0.54. In the inferior-temporal region, the arterial angle
corresponding to the largest circle (P = 0.002) was significant. Explained
variance was 0.32. CONCLUSIONS: The retinal blood vessel topography explains a
significant part of the RNFB trajectory variability but only if (1) the vessel
topography is assessed at an appropriate distance from the ONH and (2) the
superior and inferior hemifield are addressed independently.
PMID- 26436883
TI - Cell Invasion Dynamics into a Three Dimensional Extracellular Matrix Fibre
Network.
AB - The dynamics of filopodia interacting with the surrounding extracellular matrix
(ECM) play a key role in various cell-ECM interactions, but their mechanisms of
interaction with the ECM in 3D environment remain poorly understood. Based on
first principles, here we construct an individual-based, force-based
computational model integrating four modules of 1) filopodia penetration
dynamics; 2) intracellular mechanics of cellular and nuclear membranes,
contractile actin stress fibers, and focal adhesion dynamics; 3) structural
mechanics of ECM fiber networks; and 4) reaction-diffusion mass transfers of
seven biochemical concentrations in related with chemotaxis, proteolysis,
haptotaxis, and degradation in ECM to predict dynamic behaviors of filopodia that
penetrate into a 3D ECM fiber network. The tip of each filopodium crawls along
ECM fibers, tugs the surrounding fibers, and contracts or retracts depending on
the strength of the binding and the ECM stiffness and pore size. This filopodium
ECM interaction is modeled as a stochastic process based on binding kinetics
between integrins along the filopodial shaft and the ligands on the surrounding
ECM fibers. This filopodia stochastic model is integrated into migratory dynamics
of a whole cell in order to predict the cell invasion into 3D ECM in response to
chemotaxis, haptotaxis, and durotaxis cues. Predicted average filopodia speed and
that of the cell membrane advance agreed with experiments of 3D HUVEC migration
at r(2) > 0.95 for diverse ECMs with different pore sizes and stiffness.
PMID- 26436885
TI - Previous Driving Experience, but Not Vision, Is Associated With Motor Vehicle
Collision Rate in Bioptic Drivers.
AB - PURPOSE: Bioptic telescopic spectacles (BTS) consist of a small telescope (or
telescopes) mounted high in a pair of spectacle lenses. More than 40 states allow
for some form of bioptic driving licensure for people with decreased central
vision. The purpose of this study was to determine significant associations among
previous driving experience, vision, and motor vehicle collisions (MVCs) for
bioptic drivers in Ohio. METHODS: We conducted a retrospective study of patients
who received a vision examination and subsequently obtained bioptic licensure. We
obtained driving records from the Ohio Bureau of Motor Vehicles in order to
determine MVC involvement. Relationships among vision measures, age, sex,
previous experience, and MVCs were investigated using time-to-event analysis and
the Cox proportional hazards regression model. RESULTS: We identified 237 bioptic
drivers (65% male). Age at initial exam ranged from 16 to 81 years, and mean
visual acuity was approximately 20/120. The number of MVCs per driver ranged from
0 to 11, with 124 (52%) drivers having had at least one MVC. Visual acuity and
contrast sensitivity were not significant predictors of MVC. Drivers without
previous driving experience were significantly more likely to have been involved
in an MVC (P < 0.001), and this association remained significant after adjusting
for age and sex (P = 0.01). The rate of MVC per year decreased steadily over a 10
year period for drivers without previous experience. CONCLUSIONS: Previous
nonbioptic driving experience, but not visual acuity or contrast sensitivity, was
associated with yearly MVC rate in bioptic drivers.
PMID- 26436886
TI - Neurodegeneration in Type 2 Diabetes: Evidence From Spectral-Domain Optical
Coherence Tomography.
AB - PURPOSE: The purpose of this study was to assess changes in the neural retina in
eyes with different stages of diabetic retinopathy (DR) in comparison to age
matched healthy subjects. METHODS: Retrospective analysis of spectral-domain
optical coherence tomography (SD-OCT) scans of 76 naive eyes of 62 subjects with
diabetes was performed. Key exclusion criteria included presence of diabetic
macular edema, any other retinal disease, history of any treatment for DR, or
incorrect segmentation of the retinal layers on SD-OCT scans. Eyes from diabetic
patients were divided into three groups, including no DR, nonproliferative DR
(NPDR), and proliferative DR (PDR). A control group of 67 eyes of 66 age-matched
healthy volunteers was included for comparison. Average, minimum, and sectoral
thicknesses for the ganglion cell-inner plexiform layer (GCIPL) and retinal nerve
fiber layer (RNFL) were collected from both groups and compared using an ANOVA
test. RESULTS: Among the 76 included eyes, 43 had NPDR, 13 had PDR, and 20 had no
signs of DR. Average and minimum GCIPL showed significant thinning in diabetic
subjects compared with controls in all stages of DR (P < 0.05), especially
involving the papillo-macula bundle. However, GCIPL thickness was similar between
diabetic groups. There was no significant difference in average or sectoral RNFL
thicknesses among groups; however, the minimum RNFL thickness was lower in
diabetics compared with controls (P < 0.05). No relationship between GCIPL and
RNFL thicknesses and duration of diabetes was present. CONCLUSIONS: Early
thinning on the inner retina happens in type 2 diabetes, even before visible
vascular signs of DR. This supports the presence of a neurodegenerative process
in eyes of patients with diabetes and warrants neuroprotective intervention to
prevent chronic neurodegeneration. The SD-OCT may represent an indispensable tool
for identifying early signs of neurodegeneration in diabetic patients.
PMID- 26436887
TI - Residual and Dynamic Range of Retinal Nerve Fiber Layer Thickness in Glaucoma:
Comparison of Three OCT Platforms.
AB - PURPOSE: To estimate visual field (VF) sensitivity at which retinal nerve fiber
layer (RNFL) thinning reaches the measurement floor and at which RNFL stops
thinning (change points), the dynamic range of RNFL thickness, and the number of
steps from normal to RNFL floor among three optical coherence tomography (OCT)
devices. METHODS: Glaucomatous patients (n = 58) and healthy subjects (n = 55-60)
prospectively underwent VF testing and RNFL thickness measurement with Cirrus,
Spectralis, and RTVue. Change points and corresponding RNFL thicknesses were
estimated with simple linear regression (SLR) and Bayesian change point (BCP)
analyses. The dynamic range and number of steps to RNFL floor were determined.
RESULTS: The average VF change points and corresponding residual thickness at the
time RNFL stopped thinning were -22.2 dB and 57.0 MUm (Cirrus), -25.3 dB and 49.2
MUm (Spectralis), and -24.6 dB and 64.7 MUm (RTVue). The RNFL dynamic ranges
derived from SLR values were wider on Spectralis (52.6 MUm) than on Cirrus (35.4
MUm) and RTVue (35.5 MUm); the corresponding number of steps to reach the RNFL
floor were 9.0 on Cirrus, 10.6 on Spectralis, and 8.3 on RTVue. CONCLUSIONS: The
relative VF sensitivity at which average RNFL thickness reaches the measurement
floor, the residual layer thickness, and RNFL dynamic measurement range differ
among the three devices. However, the number of steps from normal to the RNFL
thickness floor is comparable.
PMID- 26436888
TI - Therapeutic Effect of Resveratrol on Oxidative Stress in Graves' Orbitopathy
Orbital Fibroblasts.
AB - PURPOSE: Multiple causative factors complicate the pathogenesis in Graves'
orbitopathy (GO). It has been suggested that oxidative stress contributes to the
development and progression of GO. Therefore, we investigated the therapeutic
effect of resveratrol, a potent antioxidant, upon oxidative stress levels in GO
orbital fibroblasts in vitro. METHODS: Orbital fibroblasts were cultured from
orbital connective tissues obtained from GO patients. Intracellular reactive
oxygen species (ROS) levels and the expression of heme oxygenase-1 (HO-1),
superoxide dismutase (SOD), catalase, and thioredoxin (Trx), were measured after
resveratrol treatment. Adipogenesis was induced, and ROS levels were examined
during adipogenic differentiation. Western blot assay was performed to evaluate
the effects of resveratrol on the expression of antioxidants levels and
transcriptional regulators. RESULTS: Treatment with 30 or 50 MUM resveratrol
reduced ROS production and HO-1 level induced by oxidative stress. Levels of
Cu/Zn-SOD, catalase, and Trx were also reduced, while Mn-SOD increased with 50
MUM resveratrol treatment. Resveratrol suppressed adipogenesis, reducing the
number of adipocytes and suppressing the accumulation of lipid droplets.
Treatment with 50 MUM resveratrol also decreased ROS levels during adipogenesis.
Expression of the transcriptional regulators phosphor-extracellular signal
regulated kinase and phospho-c-Jun NH(2)-terminal kinase significantly increased
after treatment with 50 MUM resveratrol, and decreased in response to inhibitors
of each protein. Phosphonuclear factor kappa-light-chain-enhancer of activated B
cells p65 levels also increased after treatment with 50 MUM resveratrol.
CONCLUSIONS: Resveratrol reduced ROS levels and inhibited adipogenesis in GO
orbital fibroblasts in vitro. This study supports the potential use of
resveratrol in GO treatment.
PMID- 26436890
TI - Erratum.
PMID- 26436889
TI - Allele-Specific Inhibition of Rhodopsin With an Antisense Oligonucleotide Slows
Photoreceptor Cell Degeneration.
AB - PURPOSE: To preserve photoreceptor cell structure and function in a rodent model
of retinitis pigmentosa with P23H rhodopsin by selective inhibition of the mutant
rhodopsin allele using a second generation antisense oligonucleotide (ASO).
METHODS: Wild-type mice and rats were treated with ASO by intravitreal (IVT)
injection and rhodopsin mRNA and protein expression were measured. Transgenic
rats expressing the murine P23H rhodopsin gene (P23H transgenic rat Line 1) were
administered either a mouse-specific P23H ASO or a control ASO. The contralateral
eye was injected with PBS and used as a comparator control. Electroretinography
(ERG) measurements and analyses of the retinal outer nuclear layer were conducted
and correlated with rhodopsin mRNA levels. RESULTS: Rhodopsin mRNA and protein
expression was reduced after a single ASO injection in wild-type mice with a
rhodopsin-specific ASO. Transgenic rat eyes that express a murine P23H rhodopsin
gene injected with a murine P23H ASO had a 181 +/- 39% better maximum amplitude
response (scotopic a-wave) as compared with contralateral PBS-injected eyes; the
response in control ASO eyes was not significantly different from comparator
contralateral eyes. Morphometric analysis of the outer nuclear layer showed a
significantly thicker nuclear layer in eyes injected with murine P23H ASO (18%)
versus contralateral PBS-injected eyes. CONCLUSIONS: Allele-specific ASO-mediated
knockdown of mutant P23H rhodopsin expression slowed the rate of photoreceptor
degeneration and preserved the function of photoreceptor cells in eyes of the
P23H rhodopsin transgenic rat. Our data indicate that ASO treatment is a
potentially effective therapy for the treatment of retinitis pigmentosa.
PMID- 26436891
TI - Coupled 3D Time-Dependent Wave-Packet Approach in Hyperspherical Coordinates: The
D(+)+H2 Reaction on the Triple-Sheeted DMBE Potential Energy Surface.
AB - We implement a coupled three-dimensional (3D) time-dependent wave packet
formalism for the 4D reactive scattering problem in hyperspherical coordinates on
the accurate double many body expansion (DMBE) potential energy surface (PES) for
the ground and first two singlet states (1(1)A', 2(1)A', and 3(1)A') to account
for nonadiabatic processes in the D(+) + H2 reaction for both zero and nonzero
values of the total angular momentum (J). As the long-range interactions in D(+)
+ H2 contribute significantly due to nonadiabatic effects, the convergence
profiles of reaction probabilities for the reactive noncharge transfer (RNCT),
nonreactive charge transfer (NRCT), and reactive charge transfer (RCT) processes
are shown for different collisional energies with respect to the helicity (K) and
total angular momentum (J) quantum numbers. The total and state-to-state cross
sections are presented as a function of the collision energy for the initial
rovibrational state v = 0, j = 0 of the diatom, and the calculated cross sections
compared with other theoretical and experimental results.
PMID- 26436893
TI - Molecular Factors Underlying the Deposition of Intramuscular Fat and Collagen in
Skeletal Muscle of Nellore and Angus Cattle.
AB - Studies have shown that intramuscular adipogenesis and fibrogenesis may
concomitantly occur in skeletal muscle of beef cattle. Thus, we hypothesized that
the discrepancy of intramuscular fat content in beef from Nellore and Angus was
associated with differences in intramuscular adipogenesis and fibrogenesis during
the finishing phase. To test our hypothesis, longissimus muscle samples of
Nellore (n = 6; BW = 372.5 +/- 37.3 kg) and Angus (n = 6; BW = 382.8 +/- 23.9 kg)
cattle were collected for analysis of gene and protein expression, and
quantification of intramuscular fat and collagen. Least-squares means were
estimated for the effect of Breed and differences were considered at P <= 0.05. A
greater intramuscular fat content was observed in skeletal muscle of Angus
compared to Nellore cattle (P<=0.05). No differences were observed for mRNA
expression of lipogenic and lipolytic markers ACC, FAS, FABP4, SERBP-1, CPT-2,
LPL, and ACOX (P > 0.05) in skeletal muscle of Nellore and Angus cattle.
Similarly, no differences were observed in mRNA expression of adipogenic markers
Zfp423, PPARgamma, and C/EBPalpha (P>0.05) However, a greater PPARgamma protein
content was observed in skeletal muscle of Angus compared to Nellore cattle
(P<=0.05). A greater abundance of adipo/fibrogenic cells, evaluated by the
PDGFRalpha content, was observed in skeletal muscle of Angus than Nellore cattle
(P<=0.05). No differences in fibrogenesis were observed in skeletal muscle of
Angus and Nellore cattle, which is in accordance with the lack of differences in
intramuscular collagen content in beef from both breeds (P>0.05). These findings
demonstrate that difference in intramuscular fat content is associated with a
slightly enhanced adipogenesis in skeletal muscle of Angus compared to Nellore
cattle, while no difference in fibrogenesis.
PMID- 26436892
TI - Antisense Oligonucleotide-Mediated Transcript Knockdown in Zebrafish.
AB - Antisense oligonucleotides (ASOs) are synthetic, single-strand RNA-DNA hybrids
that induce catalytic degradation of complementary cellular RNAs via RNase H.
ASOs are widely used as gene knockdown reagents in tissue culture and in Xenopus
and mouse model systems. To test their effectiveness in zebrafish, we targeted 20
developmental genes and compared the morphological changes with mutant and
morpholino (MO)-induced phenotypes. ASO-mediated transcript knockdown reproduced
the published loss-of-function phenotypes for oep, chordin, dnd, ctnnb2, bmp7a,
alk8, smad2 and smad5 in a dosage-sensitive manner. ASOs knocked down both
maternal and zygotic transcripts, as well as the long noncoding RNA (lncRNA)
MALAT1. ASOs were only effective within a narrow concentration range and were
toxic at higher concentrations. Despite this drawback, quantitation of knockdown
efficiency and the ability to degrade lncRNAs make ASOs a useful knockdown
reagent in zebrafish.
PMID- 26436894
TI - Immune Modulation of the T Cell Response in Asthma through Wnt10b.
AB - Asthma is a chronic inflammatory disease, which is characterized by activation of
CD4(+) T helper 2 cells orchestrating an allergic airway response. Whereas the
role of Wnt family members in regulating T cell maintenance and maturation is
established, their contribution to T cell activation in allergic asthma is not
known. We hypothesized that Wnt10b plays a role in the modulation of the allergic
airway response and affects T cell activation and polarization. Using an in vivo
house dust mite asthma model, Wnt10b-deficient (Wnt10b(-/-)) mice were allergen
sensitized and inflammation, as well as T cell activation, was studied in vivo
and in vitro. Wnt10b(-/-) mice exhibited an augmented inflammatory phenotype with
an increase in eosinophils in the bronchoalveolar lavage and IL-4 and IL-13 in
the lungs when compared with wild-type mice. In vitro studies confirmed an
increased T helper type 2 polarization and increased T cell activation of Wnt10b(
/-) cells. Accordingly, the percentage of naive T cells was elevated by the
addition of recombinant Wnt10b protein. Finally, Wnt10b(-/-) mice exhibited an
increase in the percentage of effector T cells in the lungs after house dust mite
sensitization, which indicated a heightened activation state, measured by an
increased percentage of CD69(hi)CD11a(hi) cells. These findings suggest that
Wnt10b plays an important role in regulating asthmatic airway inflammation
through modification of the T cell response and is a prospective target in the
disease process.
PMID- 26436895
TI - Are Structural Changes Induced by Lithium in the HIV Brain Accompanied by Changes
in Functional Connectivity?
AB - Lithium therapy has been shown to affect imaging measures of brain function and
microstructure in human immunodeficiency virus (HIV)-infected subjects with
cognitive impairment. The aim of this proof-of-concept study was to explore
whether changes in brain microstructure also entail changes in functional
connectivity. Functional MRI data of seven cognitively impaired HIV infected
individuals enrolled in an open-label lithium study were included in the
connectivity analysis. Seven regions of interest (ROI) were defined based on
previously observed lithium induced microstructural changes measured by Diffusion
Tensor Imaging. Generalized partial directed coherence (gPDC), based on time
variant multivariate autoregressive models, was used to quantify the degree of
connectivity between the selected ROIs. Statistical analyses using a linear mixed
model showed significant differences in the average node strength between pre and
post lithium therapy conditions. Specifically, we found that lithium treatment in
this population induced changes suggestive of increased strength in functional
connectivity. Therefore, by exploiting the information about the strength of
functional interactions provided by gPDC we can quantify the connectivity changes
observed in relation to a given intervention. Furthermore, in conditions where
the intervention is associated with clinical changes, we suggest that this
methodology could enable an interpretation of such changes in the context of
disease or treatment induced modulations in functional networks.
PMID- 26436897
TI - Emotional and Cognitive Influences on Pain Experience.
AB - Multiple emotional and cognitive factors impact on the experience of pain. This
chapter will review some of the most important emotional and cognitive
determinants of the pain experience as found in experimental and clinical studies
with human participants. Emotional factors that may increase pain perception are
anxiety, depression and anger. Positive emotions usually decrease perceived pain.
The cognitive factors attention, expectancy and appraisal can either increase or
decrease pain experiences depending on their specific focus and content. Many
brain regions are involved in nociceptive processing and bringing pain into
awareness. There are profound interconnections between areas processing sensory,
emotional and cognitive information. Descending pathways from cortical areas to
the midbrain and spinal levels can facilitate or inhibit spinal nociceptive
information and thereby afferent nociceptive input to the brain. The underlying
mechanisms of the various emotional and cognitive modulatory influences may
partly overlap, but also have some unique aspects. What becomes clear is that
pain is not merely a reflection of the nociceptive input, but should be
considered as a complex experience shaped by psychological factors that may be
unique for each individual.
PMID- 26436898
TI - Potential-Modulated Electrochemiluminescence of Carbon Nitride Nanosheets for
Dual-Signal Sensing of Metal Ions.
AB - As an emerging semiconductor, graphite-phase polymeric carbon nitride (GPPCN) has
drawn much attention not only in photocatalysis but also in optical sensors such
as electrochemiluminescence (ECL) sensing of metal ions. However, when the
concentrations of interfering metal ions are several times higher than that of
the target metal ion, it is almost impossible to distinguish which metal ion
changes the ECL signals in real sample detection. Herein, we report that the dual
ECL signals could be actuated by different ECL reactions merely from GPPCN
nanosheets at anodic and cathodic potentials, respectively. Interestingly, the
different metal ions exhibited distinct quenching/enhancement of the ECL signal
at different driven potentials, presumably ascribed to the diversity of energy
level matches between the metal ions and GPPCN nanosheets and catalytic
interactions of the intermediate species in ECL reactions. On this basis, without
any labeling and masking reagents, the accuracy and reliability of sensors based
on the ECL of GPPCN nanosheets toward metal ions were largely improved; thus, the
false-positive result caused by interferential metal ions could be effectively
avoided. As an example, the proposed GPPCN ECL sensor with a detection limit of
1.13 nM was successfully applied for the detection of trace Ni(2+) ion in tap and
lake water.
PMID- 26436896
TI - Quetiapine and its metabolite norquetiapine: translation from in vitro
pharmacology to in vivo efficacy in rodent models.
AB - BACKGROUND AND PURPOSE: Quetiapine has a range of clinical activity distinct from
other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in
bipolar depression, major depressive disorder and generalized anxiety disorder.
The neuropharmacological mechanisms underlying this clinical profile are not
completely understood; however, the major active metabolite, norquetiapine, has
been shown to have a distinct in vitro pharmacological profile consistent with a
broad therapeutic range and may contribute to the clinical profile of quetiapine.
EXPERIMENTAL APPROACH: We evaluated quetiapine and norquetiapine, using in vitro
binding and functional assays of targets known to be associated with
antidepressant and anxiolytic drug actions and compared these activities with a
representative range of established antipsychotics and antidepressants. To
determine how the in vitro pharmacological properties translate into in vivo
activity, we used preclinical animal models with translational relevance to
established antidepressant-like and anxiolytic-like drug action. KEY RESULTS:
Norquetiapine had equivalent activity to established antidepressants at the
noradrenaline transporter (NET), while quetiapine was inactive. Norquetiapine was
active in the mouse forced swimming and rat learned helplessness tests. In in
vivo receptor occupancy studies, norquetiapine had significant occupancy at NET
at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists
at 5-HT1A receptors, and the anxiolytic-like activity of norquetiapine in rat
punished responding was blocked by the 5-HT1A antagonist, WAY100635. CONCLUSIONS
AND IMPLICATIONS: Quetiapine and norquetiapine have multiple in vitro
pharmacological actions, and results from preclinical studies suggest that
activity at NET and 5-HT1A receptors contributes to the antidepressant and
anxiolytic effects in patients treated with quetiapine.
PMID- 26436899
TI - Cup tool use by squirrel monkeys.
AB - Captive-born male and female squirrel monkeys spontaneously 'invented' a cup tool
use technique to Contain (i.e., hold and control) food they reduced into
fragments for consumption and to Contain water collected from a valve to drink.
Food cup use was observed more frequently than water cup use. Observations
indicate that 68% (n = 39/57) of monkeys in this population used a cup (a plastic
slip cap) to Contain food, and a subset of these monkeys, 10% (n = 4/39), also
used a cup to Contain water. Cup use was optional and did not replace, but
supplemented, the hand/arm-to-mouth eating and direct valve drinking exhibited by
all members of the population. Strategies monkeys used to bring food and cups
together for food processing activity at preferred upper-level perching areas, in
the arboreal-like environment in which they lived, provides evidence that monkeys
may plan food processing activity with the cups. Specifically, prior to cup use
monkeys obtained a cup first before food, or obtained food and a cup from the
floor simultaneously, before transporting both items to upper-level perching
areas. After food processing activity with cups monkeys rarely dropped the cups
and more often placed the cups onto perching. Monkeys subsequently returned to
use cups that they previously placed on perching after food processing activity.
The latter behavior is consistent with the possibility that monkeys may keep cups
at preferred perching sites for future food processing activity and merits
experimental investigation. Reports of spontaneous tool use by squirrel monkeys
are rare and this is the first report of population-level tool use. These
findings offer insights into the cognitive abilities of squirrel monkeys and
provide a new context for behavior studies with this genus and for comparative
studies with other primates.
PMID- 26436900
TI - Human mutant huntingtin disrupts vocal learning in transgenic songbirds.
AB - Speech and vocal impairments characterize many neurological disorders. However,
the neurogenetic mechanisms of these disorders are not well understood, and
current animal models do not have the necessary circuitry to recapitulate vocal
learning deficits. We developed germline transgenic songbirds, zebra finches
(Taneiopygia guttata) expressing human mutant huntingtin (mHTT), a protein
responsible for the progressive deterioration of motor and cognitive function in
Huntington's disease (HD). Although generally healthy, the mutant songbirds had
severe vocal disorders, including poor vocal imitation, stuttering, and
progressive syntax and syllable degradation. Their song abnormalities were
associated with HD-related neuropathology and dysfunction of the cortical-basal
ganglia (CBG) song circuit. These transgenics are, to the best of our knowledge,
the first experimentally created, functional mutant songbirds. Their progressive
and quantifiable vocal disorder, combined with circuit dysfunction in the CBG
song system, offers a model for genetic manipulation and the development of
therapeutic strategies for CBG-related vocal and motor disorders.
PMID- 26436901
TI - Negligible fronto-parietal BOLD activity accompanying unreportable switches in
bistable perception.
AB - The human brain's executive systems have a vital role in deciding and selecting
among actions. Selection among alternatives also occurs in the perceptual domain;
for instance, when perception switches between interpretations during perceptual
bistability. Whether executive systems also underlie this functionality remains
debated, with known fronto-parietal concomitants of perceptual switches being
variously interpreted as reflecting the switches' cause or as reflecting their
consequences. We developed a procedure in which the two eyes receive different
inputs and perception demonstrably switches between these inputs, yet the
switches themselves are so inconspicuous as to become unreportable, minimizing
their executive consequences. Fronto-parietal fMRI BOLD responses that
accompanied perceptual switches were similarly minimized in this procedure,
indicating that these reflect the switches' consequences rather than their cause.
We conclude that perceptual switches do not always rely on executive brain areas
and that processes responsible for selection among alternatives may operate
outside the brain's executive systems.
PMID- 26436902
TI - Flexible gating of contextual influences in natural vision.
AB - Identical sensory inputs can be perceived as markedly different when embedded in
distinct contexts. Neural responses to simple stimuli are also modulated by
context, but the contribution of this modulation to the processing of natural
sensory input is unclear. We measured surround suppression, a quintessential
contextual influence, in macaque primary visual cortex with natural images. We
found that suppression strength varied substantially for different images. This
variability was not well explained by existing descriptions of surround
suppression, but it was predicted by Bayesian inference about statistical
dependencies in images. In this framework, surround suppression was flexible: it
was recruited when the image was inferred to contain redundancies and
substantially reduced in strength otherwise. Thus, our results reveal a gating of
a basic, widespread cortical computation by inference about the statistics of
natural input.
PMID- 26436903
TI - Perceptual learning in autism: over-specificity and possible remedies.
AB - Inflexible behavior is a core characteristic of autism spectrum disorder (ASD),
but its underlying cause is unknown. Using a perceptual learning protocol, we
observed initially efficient learning in ASD that was followed by anomalously
poor learning when the location of the target was changed (over-specificity).
Reducing stimulus repetition eliminated over-specificity. Our results indicate
that inflexible behavior may be evident ubiquitously in ASD, even in sensory
learning, but can be circumvented by specifically designed stimulation protocols.
PMID- 26436905
TI - High-resolution high-sensitivity elemental imaging by secondary ion mass
spectrometry: from traditional 2D and 3D imaging to correlative microscopy.
AB - Secondary ion mass spectrometry (SIMS) constitutes an extremely sensitive
technique for imaging surfaces in 2D and 3D. Apart from its excellent sensitivity
and high lateral resolution (50 nm on state-of-the-art SIMS instruments),
advantages of SIMS include high dynamic range and the ability to differentiate
between isotopes. This paper first reviews the underlying principles of SIMS as
well as the performance and applications of 2D and 3D SIMS elemental imaging. The
prospects for further improving the capabilities of SIMS imaging are discussed.
The lateral resolution in SIMS imaging when using the microprobe mode is limited
by (i) the ion probe size, which is dependent on the brightness of the primary
ion source, the quality of the optics of the primary ion column and the electric
fields in the near sample region used to extract secondary ions; (ii) the
sensitivity of the analysis as a reasonable secondary ion signal, which must be
detected from very tiny voxel sizes and thus from a very limited number of
sputtered atoms; and (iii) the physical dimensions of the collision cascade
determining the origin of the sputtered ions with respect to the impact site of
the incident primary ion probe. One interesting prospect is the use of SIMS-based
correlative microscopy. In this approach SIMS is combined with various high
resolution microscopy techniques, so that elemental/chemical information at the
highest sensitivity can be obtained with SIMS, while excellent spatial resolution
is provided by overlaying the SIMS images with high-resolution images obtained by
these microscopy techniques. Examples of this approach are given by presenting in
situ combinations of SIMS with transmission electron microscopy (TEM), helium ion
microscopy (HIM) and scanning probe microscopy (SPM).
PMID- 26436906
TI - Targeted alpha therapy for cancer: where we are today and where we are heading.
PMID- 26436904
TI - Depletion of microglia and inhibition of exosome synthesis halt tau propagation.
AB - Accumulation of pathological tau protein is a major hallmark of Alzheimer's
disease. Tau protein spreads from the entorhinal cortex to the hippocampal region
early in the disease. Microglia, the primary phagocytes in the brain, are
positively correlated with tau pathology, but their involvement in tau
propagation is unknown. We developed an adeno-associated virus-based model
exhibiting rapid tau propagation from the entorhinal cortex to the dentate gyrus
in 4 weeks. We found that depleting microglia dramatically suppressed the
propagation of tau and reduced excitability in the dentate gyrus in this mouse
model. Moreover, we demonstrate that microglia spread tau via exosome secretion,
and inhibiting exosome synthesis significantly reduced tau propagation in vitro
and in vivo. These data suggest that microglia and exosomes contribute to the
progression of tauopathy and that the exosome secretion pathway may be a
therapeutic target.
PMID- 26436907
TI - A new chapter.
PMID- 26436909
TI - Air pollution and children's respiratory health.
PMID- 26436910
TI - Empowering family physicians to impart proper inhaler teaching to patients with
chronic obstructive pulmonary disease and asthma.
AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) and asthma
depend on inhalers for management, but critical errors committed during inhaler
use can limit drug effectiveness. Outpatient education in inhaler technique
remains inconsistent due to limited resources and inadequate provider knowledge.
OBJECTIVE: To determine whether a simple, two-session inhaler education program
can improve physician attitudes toward inhaler teaching in primary care practice.
METHODS: An inhaler education program with small-group hands-on device training
was instituted for family physicians (FP) in British Columbia and Alberta.
Sessions were spaced one to three months apart. All critical errors were
corrected in the first session. Questionnaires surveying current inhaler teaching
practices and attitudes toward inhaler teaching were distributed to physicians
before and after the program. RESULTS: Forty-one (60%) of a total 68
participating FPs completed both before and after program questionnaires. Before
the program, only 20 (49%) reported providing some form of inhaler teaching in
their practices, and only four (10%) felt fully competent to teach patients
inhaler technique. After the program, 40 (98%) rated their inhaler teaching as
good to excellent. Thirty-four (83%) reported providing inhaler teaching in their
practices, either by themselves or by an allied health care professional they had
personally trained. All stated they could teach inhaler technique within 5 min.
Observation of FPs during the second session by certified respiratory educators
found that none made critical errors and all had excellent technique. CONCLUSION:
A physician inhaler education program can improve attitudes toward inhaler
teaching and facilitate implementation in clinical practices.
PMID- 26436911
TI - Corticosteroid therapy in critical illness due to seasonal and pandemic
influenza.
AB - BACKGROUND: Survey data suggest that Canadian intensivists administer
corticosteroids to critically ill patients primarily in response to airway
obstruction, perceived risk for adrenal insufficiency and hemodynamic
instability. OBJECTIVE: To describe variables independently associated with
systemic corticosteroid therapy during an influenza outbreak. METHODS: The
present analysis was retrospective cohort study involving critically ill patients
with influenza in two Canadian cities. Hospital records were reviewed for
critically ill patients treated in the intensive care units (ICUs) of eight
hospitals in Canada during the 2008 to 2009 and 2009 to 2010 influenza outbreaks.
Abstracted data included demographic information, symptoms at disease onset,
chronic comorbidities and baseline illness severity scores. Corticosteroid use
data were extracted for every ICU day and expressed as hydrocortisone dose
equivalent in mg. Multivariable regression models were constructed to identify
variables independently associated with corticosteroid therapy in the ICU.
RESULTS: The study cohort included 90 patients with a mean (+/- SD) age of 55.0
+/- 17.3 years and Acute Physiology and Chronic Health Evaluation II score of
19.8 +/- 8.3. Patients in 2009 to 2010 were younger with more severe lung injury
but similar exposure to corticosteroids. Overall, 54% of patients received
corticosteroids at a mean daily dose of 343 +/- 330 mg of hydrocortisone for 8.5
+/- 4.8 days. Variables independently associated with corticosteroid therapy in
the ICU were history of airway obstruction (OR 4.8 [95% CI 1.6 to 14.9]) and
hemodynamic instability (OR 4.6 [95% CI 1.2 to 17.8]). CONCLUSION: Observational
data revealed that hemodynamic instability and airway obstruction were associated
with corticosteroid therapy in the critical care setting, similar to a recent
survey of stated practice. Efforts to determine the effects of corticosteroids in
the ICU for these specific clinical situations are warranted.
PMID- 26436912
TI - Past, present and future of respiratory research: A survey of Canadian health
care professionals.
AB - BACKGROUND: The Canadian Respiratory Health Professionals (CRHP) is the
multidisciplinary health care professional group of the Canadian Lung
Association. Although the CRHP has a growing number of highly qualified
researchers, the landscape of their research in Canada has not been described.
OBJECTIVES: To describe the level of respiratory research engagement; identify
barriers and facilitators to research engagement; describe the experience and
interest in developing research skills; and identify priority areas of future
respiratory research among health care professionals. METHODS: An online survey
of CRHP members was used to collect demographic information; barriers and
facilitators to conducting research; future directions in respiratory research;
and research funding and mentorship. Experience with and interest in 'upskilling'
research skills were also evaluated. RESULTS: A total of 119 surveys were
completed (22% response rate), of which 69 (58%) respondents were engaged in
respiratory research. Reasons for not being involved in respiratory research were
lack of mentorship, support and funding. The top research areas were chronic
obstructive pulmonary disease (74%) and asthma (41%). The top facilitators for
research engagement were amount of funding (29%) and mentorship (28%).
Respondents in research positions rated their experience in research skills as
high; those in nonresearch positions as low. However, both groups expressed
interest in improving their research skills. CONCLUSIONS: Areas of development,
such as research skills, greater funding opportunities and mentorship to increase
the research capacity of health care professionals in respiratory health were
identified. Health professional researchers have an important role in the
national respiratory research strategy to increase interdisciplinary engagement
and build collaborative teams.
PMID- 26436913
TI - Povidone Iodine Rectal Preparation at Time of Prostate Needle Biopsy is a Simple
and Reproducible Means to Reduce Risk of Procedural Infection.
AB - Single institution and population-based studies highlight that infectious
complications following transrectal ultrasound guided prostate needle biopsy
(TRUS PNB) are increasing. Such infections are largely attributable to quinolone
resistant microorganisms which colonize the rectal vault and are translocated
into the bloodstream during the biopsy procedure. A povidone iodine rectal
preparation (PIRP) at time of biopsy is a simple, reproducible method to reduce
rectal microorganism colony counts and therefore resultant infections following
TRUS PNB. All patients are administered three days of oral antibiotic therapy
prior to biopsy. The PIRP technique involves initially positioning the patient in
the standard manner for a TRUS PNB. Following digital rectal examination, 15 ml
of a 10% solution of commercially available povidone iodine is mixed with 5 ml of
1% lidocaine jelly to create slurry. A 4 cmx4 cm sterile gauze is soaked in this
slurry and then inserted into the rectal vault for 2 min after which it is
removed. Thereafter, a disposable cotton gynecologic swab is used to paint both
the perianal area and the rectal vault to a distance of 3 cm from the anus. The
povidone iodine solution is then allowed to dry for 2-3 min prior to proceeding
with standard transrectal ultrasonography and subsequent biopsy. This PIRP
technique has been in practice at our institution since March of 2012 with an
associated reduction of post-biopsy infections from 4.3% to 0.6% (p=0.02). The
principal advantage of this prophylaxis regimen is its simplicity and
reproducibility with use of an easily available, inexpensive agent to reduce
infections. Furthermore, the technique avoids exposing patients to additional
systemic antibiotics with potential further propagation of multi-drug resistant
organisms. Usage of PIRP at TRUS PNB, however, is not applicable for patients
with iodine or shellfish allergies.
PMID- 26436914
TI - Animal Models for the Study of Comorbid Pain and Psychiatric Disorders.
AB - Animal models of chronic pain have provided valuable information on the
mechanisms of initiation and maintenance of the disease. Much of the research
effort has targeted sensory abnormalities like hyperalgesia and allodynia.
However, in the past 15 years a significant number of research groups have
focused their attention on comorbid anxiety, depression and cognitive impairments
that frequently emerge in chronic pain conditions. A myriad of paradigms have
since then been introduced in the field to tackle multiple dimensions of rodents'
behavior. Concerning emotional behavior, these include the elevated plus (and
zero) maze and dark/light box for anxiety, the forced swimming and tail
suspension tests for depression, and the spontaneous burrowing behavior for
general well-being. Regarding the cognitive dimension, several water mazes
(spatial-reference memory), attentional set-shifting test (attention and reversal
learning), novel object recognition (memory), 5-choice serial reaction time task
(sustained attention) and variable delay-to-signal task (impulsivity) are among
the most commonly employed paradigms. The construct of some of these paradigms in
the context of chronic pain will be reviewed in this chapter, with special
emphasis on mood and cognitive alterations that are associated with the
development of neuropathic and arthritic pain.
PMID- 26436915
TI - Assessing Biases in the Evaluation of Classification Assays for HIV Infection
Recency.
AB - Identifying recent HIV infection cases has important public health and clinical
implications. It is essential for estimating incidence rates to monitor epidemic
trends and evaluate the effectiveness of interventions. Detecting recent cases is
also important for HIV prevention given the crucial role that recently infected
individuals play in disease transmission, and because early treatment onset can
improve the clinical outlook of patients while reducing transmission risk.
Critical to this enterprise is the development and proper assessment of accurate
classification assays that, based on cross-sectional samples of viral sequences,
help determine infection recency status. In this work we assess some of the
biases present in the evaluation of HIV recency classification algorithms that
rely on measures of within-host viral diversity. Particularly, we examine how the
time since infection (TSI) distribution of the infected subjects from which viral
samples are drawn affect performance metrics (e.g., area under the ROC curve,
sensitivity, specificity, accuracy and precision), potentially leading to
misguided conclusions about the efficacy of classification assays. By comparing
the performance of a given HIV recency assay using six different TSI
distributions (four simulated TSI distributions representing different epidemic
scenarios, and two empirical TSI distributions), we show that conclusions about
the overall efficacy of the assay depend critically on properties of the TSI
distribution. Moreover, we demonstrate that an assay with high overall
classification accuracy, mainly due to properly sorting members of the well
represented groups in the validation dataset, can still perform notoriously
poorly when sorting members of the less represented groups. This is an inherent
issue of classification and diagnostics procedures that is often
underappreciated. Thus, this work underscores the importance of acknowledging and
properly addressing evaluation biases when proposing new HIV recency assays.
PMID- 26436916
TI - Under What Circumstances Do Wood Products from Native Forests Benefit Climate
Change Mitigation?
AB - Climate change mitigation benefits from the land sector are not being fully
realised because of uncertainty and controversy about the role of native forest
management. The dominant policy view, as stated in the IPCC's Fifth Assessment
Report, is that sustainable forest harvesting yielding wood products, generates
the largest mitigation benefit. We demonstrate that changing native forest
management from commercial harvesting to conservation can make an important
contribution to mitigation. Conservation of native forests results in an
immediate and substantial reduction in net emissions relative to a reference case
of commercial harvesting. We calibrated models to simulate scenarios of native
forest management for two Australian case studies: mixed-eucalypt in New South
Wales and Mountain Ash in Victoria. Carbon stocks in the harvested forest
included forest biomass, wood and paper products, waste in landfill, and
bioenergy that substituted for fossil fuel energy. The conservation forest
included forest biomass, and subtracted stocks for the foregone products that
were substituted by non-wood products or plantation products. Total carbon stocks
were lower in harvested forest than in conservation forest in both case studies
over the 100-year simulation period. We tested a range of potential parameter
values reported in the literature: none could increase the combined carbon stock
in products, slash, landfill and substitution sufficiently to exceed the increase
in carbon stock due to changing management of native forest to conservation. The
key parameters determining carbon stock change under different forest management
scenarios are those affecting accumulation of carbon in forest biomass, rather
than parameters affecting transfers among wood products. This analysis helps
prioritise mitigation activities to focus on maximising forest biomass.
International forest-related policies, including negotiations under the UNFCCC,
have failed to recognize fully the mitigation value of native forest
conservation. Our analyses provide evidence for decision-making about the
circumstances under which forest management provides mitigation benefits.
PMID- 26436917
TI - Application of LogitBoost Classifier for Traceability Using SNP Chip Data.
AB - Consumer attention to food safety has increased rapidly due to animal-related
diseases; therefore, it is important to identify their places of origin (POO) for
safety purposes. However, only a few studies have addressed this issue and
focused on machine learning-based approaches. In the present study,
classification analyses were performed using a customized SNP chip for POO
prediction. To accomplish this, 4,122 pigs originating from 104 farms were
genotyped using the SNP chip. Several factors were considered to establish the
best prediction model based on these data. We also assessed the applicability of
the suggested model using a kinship coefficient-filtering approach. Our results
showed that the LogitBoost-based prediction model outperformed other classifiers
in terms of classification performance under most conditions. Specifically, a
greater level of accuracy was observed when a higher kinship-based cutoff was
employed. These results demonstrated the applicability of a machine learning
based approach using SNP chip data for practical traceability.
PMID- 26436919
TI - Review of bioaerosols in indoor environment with special reference to sampling,
analysis and control mechanisms.
AB - Several tiny organisms of various size ranges present in air are called airborne
particles or bioaerosol which mainly includes live or dead fungi and bacteria,
their secondary metabolites, viruses, pollens, etc. which have been related to
health issues of human beings and other life stocks. Bio-terror attacks in 2001
as well as pandemic outbreak of flue due to influenza A H1N1 virus in 2009 have
alarmed us about the importance of bioaerosol research. Hence characterization
i.e. identification and quantification of different airborne microorganisms in
various indoor environments is necessary to identify the associated risks and to
establish exposure threshold. Along with the bioaerosol sampling and their
analytical techniques, various literatures revealing the concentration levels of
bioaerosol have been mentioned in this review thereby contributing to the
knowledge of identification and quantification of bioaerosols and their different
constituents in various indoor environments (both occupational and non
occupational sections). Apart from recognition of bioaerosol, developments of
their control mechanisms also play an important role. Hence several control
methods have also been briefly reviewed. However, several individual levels of
efforts such as periodic cleaning operations, maintenance activities and proper
ventilation system also serve in their best way to improve indoor air quality.
PMID- 26436918
TI - Progestins Upregulate FKBP51 Expression in Human Endometrial Stromal Cells to
Induce Functional Progesterone and Glucocorticoid Withdrawal: Implications for
Contraceptive- Associated Abnormal Uterine Bleeding.
AB - Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and
highly effective family planning method. Abnormal uterine bleeding (AUB) is the
major side effect of, and cause for, discontinuation of LAPCs. The endometria of
LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased
endometrial blood flow and oxidative stress. To understanding to mechanisms
underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in
human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured
HESCs treated 7 days with estradiol (E2) or E2+ medroxyprogesterone acetate (MPA)
or E2+ etonogestrel (ETO) or E2+ progesterone (P4) were analyzed by quantitative
Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained
paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and
ovariectomized guinea pigs (GPs) treated with placebo or E2 or MPA or E2+MPA for
21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by
all three progestins, whereas a 235 gene group was regulated by E2+ETO and
E2+MPA, but not E2+P4. Ingenuity pathway analysis identified glucocorticoid
receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO
specific genes. Among these, microarray results demonstrated significant
enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA
and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In
endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was
significantly increased in endometrial stromal and glandular cells. In GPs,
E2+MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial
stromal and glandular cells versus placebo- and E2-administered groups. MPA or
ETO administration activates GR signaling and increases endometrial FKBP51
expression, which could be one of the mechanisms causing AUB by inhibiting PR and
GR-mediated transcription. The resultant PR and/or GR-mediated functional
withdrawal may contribute to associated endometrial inflammation, aberrant
angiogenesis, and bleeding.
PMID- 26436921
TI - Regioselective Substitution at the 1,3- and 6,8-Positions of Pyrene for the
Construction of Small Dipolar Molecules.
AB - This article presents a novel asymmetrical functionalization strategy for the
construction of dipolar molecules via efficient regioselective functionalization
along the Z-axis of pyrene at both the 1,3- and 6,8-positions. Three
asymmetrically substituted 1,3-diphenyl-6,8-R-disubsituted pyrenes were fully
characterized by X-ray crystallography, photophysical properties,
electrochemistry, and density functional theory calculations.
PMID- 26436922
TI - Mosaic deletion of 20pter due to rescue by somatic recombination.
AB - We report on a unique case of a mosaic 20pter-p13 deletion due to a somatic
repair event identified by allele differentiating single nucleotide polymorphism
(SNP) probes on chromosomal microarray. Small terminal deletions of 20p have been
reported in a few individuals and appear to result in a variable phenotype. This
patient was a 24-month-old female who presented with failure to thrive and speech
delay. Chromosomal microarray analysis (CMA) performed on peripheral blood showed
a 1.6 Mb deletion involving the terminus of 20p (20pter-20p13). This deletion
appeared mosaic by CMA and this suspicion was confirmed by fluorescence in situ
hybridization (FISH) analysis. Additionally, the deletion interval at 20p was
directly adjacent to 15 Mb of mosaic copy-neutral loss of heterozygosity (LOH).
The pattern of SNP probes was highly suggestive of a somatic repair event that
resulted in rescue of the deleted region using the non-deleted homologue as a
template. Structural mosaicism is rare and most often believed to be due to a
postzygotic mechanism. This case demonstrates the additional utility of allele
patterns to help distinguish mechanisms and in this case identified the
possibility of either a post-zygotic repair of a germline deletion or a post
zygotic deletion with somatic recombination repair in a single step.
PMID- 26436920
TI - miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control
profibrogenic macrophage program.
AB - Macrophages play a pivotal role in tissue fibrogenesis, which underlies the
pathogenesis of many end-stage chronic inflammatory diseases. MicroRNAs are key
regulators of immune cell functions, but their roles in macrophage's fibrogenesis
have not been characterized. Here we show that IL-4 and IL-13 induce miR-142-5p
and downregulate miR-130a-3p in macrophages; these changes sustain the
profibrogenic effect of macrophages. In vitro, miR-142-5p mimic prolongs STAT6
phosphorylation by targeting its negative regulator, SOCS1. Blocking miR-130a
relieves its inhibition of PPARgamma, which coordinates STAT6 signalling. In
vivo, inhibiting miR-142-5p and increasing miR-130a-3p expression with locked
nucleic acid-modified oligonucleotides inhibits CCL4-induced liver fibrosis and
bleomycin-induced lung fibrosis in mice. Furthermore, macrophages from the tissue
samples of patients with liver cirrhosis and idiopathic pulmonary fibrosis
display increased miR-142-5p and decreased miR-130a-3p expression. Therefore, miR
142-5p and miR-130a-3p regulate macrophage profibrogenic gene expression in
chronic inflammation.
PMID- 26436923
TI - [Influence of weight gain during the first year after kidney transplantation in
the survival of grafts and patients].
AB - BACKGROUND: After receiving a kidney allograft, patients tend to gain weight
acquiring the risk associated with overweight and obesity. AIM: To compare the
evolution during 10 years after transplantation of patients who gained more than
15% of their initial weight during the first year after receiving the graft with
those who did not experience this increase. MATERIAL AND METHODS: Cohort study of
182 patients transplanted in a single hospital between 1981 and 2003. Demographic
data, weight gain during the first year, drugs used, complications and evolution
of patients and grafts were recorded. RESULTS: Seventy two patients gained more
than 15% of their weight during the first year. These were discharged after
receiving the graft with a lower serum creatinine than their counterparts (1.46
+/- 0.71 and 1.97 +/- 1.74 mg/dl respectively, p = 0.02). Ten years mortality
with a functioning kidney was higher among weight gainers (25 and 12.7%
respectively, p = 0.03). No other differences were observed between groups.
CONCLUSIONS: Patients who gained more than 15% of their initial weight during the
first year after receiving a kidney graft have a higher 10 years mortality with a
functioning kidney.
PMID- 26436924
TI - [Effects of an intervention to reduce cardiovascular risk factors in university
students].
AB - BACKGROUND: Interventions aiming to reduce obesity and sedentary behaviors in
young adults could be a feasible and effective approach to prevent cardiovascular
diseases. AIM: To evaluate the effect of a lifestyle-based intervention on
reducing cardiovascular risk factors in university students. MATERIAL AND
METHODS: Sixty university students aged 21 +/- 1 years (n = 44 females) took part
on a 17 weeks lifestyle intervention consisting in education about healthy
lifestyles and physical training, during a curricular course about health
promotion and healthy lifestyles. At baseline and at the end of the intervention
participants completed a lifestyles questionnaire and provided fasting blood
samples to quantify glucose and lipids profile. RESULTS: After the intervention
significant reductions in the prevalence of hyperglycemia (-10.0%), high blood
pressure (-16.7%) and physical inactivity (-26.7%) were observed. Moreover, a
significant reduction in body weight, waist circumference, blood pressure, total
cholesterol, triglycerides and an increase in HDL cholesterol were observed after
intervention. CONCLUSIONS: The implementation of an intervention to promote
healthy lifestyles is an effective way of reducing cardiovascular risk factors in
university students.
PMID- 26436925
TI - [An analysis of Chilean biomedical publications in PubMed in the years 2008
2009].
AB - BACKGROUND: During the years 2008 and 2009, 1,191 biomedical articles authored by
Chilean investigators working in Chile were indexed in PubMed. AIMS: To evaluate
the potential visibility of those articles, according to scientometric indexes of
the journals where they were published. METHODS: Those journals where the
articles had been published were identified and each journal?s Impact Factor
(JIF), 5-year JIF, SCImago Journal Rank (SJR), SCImago Quartiles (Q) for 2010 and
the Source Normalized Impact per Paper (SNIP) for 2008-2009 were identified.
RESULTS: Three hundred and twelve articles (26,2%) were dedicated to experimental
studies in animals, tissues or cells and they were classified as ?Biomedicine?,
while 879 (73,8%) were classified as ?Clinical Medicine?; in both areas the main
type of articles were original reports (90% and 73.6%, respectively). Revista
Medica de Chile and Revista Chilena de Infectologia concentrated the greater
number of publications. Articles classified in Biomedicine were published more
frequently in English and in journals with higher scientometric indexes than
those classified in Clinical Medicine. CONCLUSIONS: Biomedical articles dealing
with clinical topics, particularly case reports, were published mostly in
national journals or in foreign journals with low scientometric indexes. It can
be partly attributable to the authors? interest in reaching local readers. The
evaluation of research productivity should combine several scientometric indexes,
selected according to the field of research, the institution's and investigators?
interests, with a qualitative and multifactorial assessment.
PMID- 26436926
TI - [Social security and labor absenteeism in a regional health service].
AB - BACKGROUND: Absenteism can generate important economic costs. AIM: To analyze the
determinants of the time off work for sick leaves granted to workers of a
regional health service. MATERIAL AND METHODS: Information about 2033
individuals, working at a health service, that were granted at least one sick
leave during 2012, was analyzed. Personal identification was censored. Special
emphasis was given to the type of health insurance system of the workers (public
or private). RESULTS: Workers ascribed to the Chilean public health insurance
system (FONASA) had 11 days more off work than their counterparts ascribed to
private health insurance systems. A higher amount of time off work was observed
among older subjects and women. CONCLUSIONS: Age, gender and the type of health
insurance system influence the number of day off work due to sick leaves.
PMID- 26436927
TI - [Association of grip strength with gender age and handedness in 116 older
people].
AB - BACKGROUND: Hand grip strength could be influenced by gender, age and handedness.
AIM: To describe differences in grip strength for age, gender and upper extremity
handedness in non-disabled community-dwelling older adults. MATERIAL AND METHODS:
We studied 47 males aged 72.3 +/- 5.6 years and 69 females 72.4 +/- 6.0 years who
were divided in two age groups (65-70 and >= 71 years old). Grip strength was
determined by a standardized protocol using a hand dynamometer. RESULTS: There
was an inverse correlation between grip strength and age in both hands only among
men (p <= 0.05). When analyzing both genders, there was a significant inverse
correlation between grip strength and age only in the dominant hand (p <= 0.05).
Strength was higher in the dominant hand in both genders (p <= 0.05). It was also
higher in men, compared to women in the two age groups studied (p <= 0.05).
CONCLUSIONS: Grip strength is higher in men than women, it decreases with age and
is higher in the dominant hand.
PMID- 26436928
TI - [Usefulness of antimicrobial prophylaxis with ciprofloxacin prior to flexible
cystoscopy].
AB - BACKGROUND: Flexible cystoscopy is a common test in clinical practice done with
or without antibiotic prophylaxis. AIM: To evaluate the efficacy of antibiotic
prophylaxis with ciprofloxacin to reduce the incidence of urinary infection.
MATERIAL AND METHODS: Prospective, non-randomized observational study that
included 60 patients divided into two groups. Group 1 received prophylactic
ciprofloxacin 500 mg, one hour prior to the procedure and group 2 did not receive
prophylaxis. The presence of bacteriuria, symptoms or signs of urinary infection
or attending Emergency rooms or primary care for these symptoms were recorded
during the seven days after the cystoscopy. RESULTS: In groups 1 and 2, four and
one patients had a positive urine culture, respectively. Only one patient in
group 1 consulted in primary care for symptoms. No significant differences in
symptoms or signs of urinary infection between groups were observed. CONCLUSIONS:
In this group of patients, antibiotic prophylaxis with ciprofloxacin 500 mg prior
to cystoscopy had no benefit.
PMID- 26436929
TI - [Development of MEDUC-PG14 survey to assess postgraduate teaching in medical
specialties].
AB - BACKGROUND: Feedback is one of the most important tools to improve teaching in
medical education. AIM: To develop an instrument to assess the performance of
clinical postgraduate teachers in medical specialties. MATERIAL AND METHODS: A
qualitative methodology consisting in interviews and focus-groups followed by a
quantitative methodology to generate consensus, was employed. After generating
the instrument, psychometric tests were performed to assess the construct
validity (factor analysis) and reliability (Cronbach?s alpha). RESULTS: Experts
in medical education, teachers and residents of a medical school participated in
interviews and focus groups. With this information, 26 categories (79 items) were
proposed and reduced to 14 items (Likert scale 1-5) by an expert?s Delphi panel,
generating the MEDUC-PG14 survey, which was answered by 123 residents from
different programs of medical specialties. Construct validity was carried out.
Factor analysis showed three domains: Teaching and evaluation, respectful
behavior towards patients and health care team, and providing feedback. The
global score was 4.46 +/- 0.94 (89% of the maximum). One teachers? strength, as
evaluated by their residents was ?respectful behavior? with 4.85 +/- 0.42 (97% of
the maximum). ?Providing feedback? obtained 4.09 +/- 1.0 points (81.8% of the
maximum). MEDUC-PG14 survey had a Cronbach?s alpha coefficient of 0.947.
CONCLUSIONS: MEDUC-PG14 survey is a useful and reliable guide for teacher
evaluation in medical specialty programs. Also provides feedback to improve
educational skills of postgraduate clinical teachers.
PMID- 26436930
TI - [Legal recognition of transsexuality in Chile through the judicial procedure for
name change].
AB - Do transsexual people in Chile have a right to have their gender identity or
their sex reassignment legally recognized? The absence of any legislation on
gender identity or transsexualism could lead us to believe that it is not the
case. However, a quantitative review of decisions issued by Chilean courts during
the last years on name-and sex-change requests filed by transsexual people
reveals that most of these courts have accepted these requests. From the
perspective of the well-being of transsexual people, this is a positive result.
However, the fact that a few rejections exist reminds us of the need to enact an
explicit legislation in this issue. Lastly, a qualitative analysis of those
decisions suggests that the traditional reluctance of courts to interpret the law
in a creative way has been overcome in these cases by the use of knowledge and
discourses belonging to healthcare sciences. This is an example of an
epistemological complementariness between medicine and law.
PMID- 26436931
TI - [Opinions of medical students about complementary therapies].
AB - BACKGROUND: There is increasing national and worldwide interest on complementary
therapies (CT). AIM: To describe and analyze the opinions and interest about CT
among medical students. MATERIAL AND METHODS: An anonymous and voluntary survey
with questions used in previous studies, was applied to students from first to
fifth year. RESULTS: The survey was answered by 526 medical students,
corresponding to 86% of the target population. The students knew about an average
of 4.7 therapies, out of 12 displayed. The better known therapy was acupuncture,
followed by homeopathy and reiki, which raised the greater interest. The
knowledge and interest was higher among women, who also had a more favorable
opinion about CT. The interest decreases and the proportion of unfavorable
opinions increases among students of upper level courses. Forty nine percent of
respondents have used CT for themselves and 22% had no experience whatsoever with
them. CONCLUSIONS: In general, there is an appreciable knowledge, experience,
interest and positive opinions toward CT. This favorable attitude is higher in
women and decreases as career progresses. Medical students consider that they
should have some approach to CT during their career.
PMID- 26436932
TI - [Job satisfaction and organizational culture as predictors of absenteeism].
AB - BACKGROUND: Absenteeism caused by sick leaves generates an important economic
burden. AIM: To determine if job satisfaction, psychological climate, hierarchic
level and age are predictors of absenteeism caused by sick leaves. MATERIAL AND
METHODS: FOCUS-93 survey that measures organizational culture and the
satisfaction scale of Warr, Cook and Wall were distributed to 1387 workers of a
hospital and answered by 874. Absenteeism data was obtained from the justified
absenteeism registry of the Chilean Health Services. RESULTS: Absenteeism is
influenced by job satisfaction and organizational culture. Age has no influence.
Hierarchic level has a negative influence on absenteeism among men and a
negligible effect among women. CONCLUSIONS: Those workers that are not satisfied
with their work have higher rates of absenteeism.
PMID- 26436933
TI - [Graves? orbitopathy in pediatrics].
AB - Graves? orbitopathy (GO) is rare in pediatric patients, however is the most
common extrathyroid manifestation of Graves? disease (GD), being present in 30
67% of patients. GO is an autoimmune inflammatory disorder involving orbital
connective and fatty tissues as well as the extraocular muscles. In children, GO
is less common and less severe than in adults. The most common symptoms are upper
eyelid retraction, conjunctival injection, and proptosis and periorbital edema.
Severe complications include dysthyroid optic neuropathy, corneal ulceration and
eyeball subluxation. The diagnosis is established by clinical, laboratory and
imaging findings. There are no management guidelines for GO in children but adult
recommendations include the assessment of clinical activity and its severity, to
implement the best treatment. Supportive therapies are intended to relieve
symptoms and prevent corneal damage in mild cases. Tobacco exposure should also
be avoided. The first line of treatment is systemic administration of
corticosteroids in active and severe cases. Other options as somatostatin use and
retrobulbar radiation have not been used in children, therefore their use is not
recommended.
PMID- 26436934
TI - [Autoimmune diseases in type 1A diabetes mellitus].
AB - Type 1A diabetes (DM1A) is an autoimmune disease that comprises 10% of patients
with diabetes mellitus. Its frequency is gradually increasing in countries like
Mexico. Patients with DM1A commonly have hypothyroidism, Addison disease, celiac
disease and less common diseases such as polyglandular syndrome. These diseases
are related to susceptibility genes such as HLA, CTLA-4 and PTPN22, which induce
central and peripheral immunologic tolerance. This review article emphasizes the
importance of searching other autoimmune diseases in patients with DM1A, to
improve their prognosis and quality of life.
PMID- 26436935
TI - [Therapeutic monitoring of antibiotics: New methodologies: biosensors].
AB - The pharmacokinetics of antibiotics, especially in severely ill patients, may be
profoundly altered due to multiple pathophysiological changes. Recent studies
have shown that empiric dosing recommendations for ICU patients are inadequate to
effectively treat a broad range of susceptible organisms and need to be
reconsidered. Therapeutic drug monitoring (TDM) is an important mean for
optimizing drug utilization and doses for the purpose of improving the clinical
effectiveness. However, it is very challenging to quantify plasma antibiotic
concentrations in clinical situations as a routine practice, because of the high
costs and complexities associated with advanced instrumental techniques.
Currently there are not routine and low cost methods to determine the presence
and concentration of beta-lactam antibiotics in plasma patients in a clinical
setup. Indeed, such analytical methods are based on chromatographic techniques
mainly used in research. Here we describe and comment different techniques,
focusing on our preliminary experience using biosensors.
PMID- 26436936
TI - [A standardized practical examination for title revalidation of graduates of
foreign medical schools].
AB - BACKGROUND: The University of Chile, backed by its extensive experience in
Objective Structured Clinical Examinations (OSCEs), performs the practical exam
to graduates of foreign medical school in this format. This test format would
give more guarantees of validity and fairness as compared with the previous oral
examination that was required for title revalidation. AIM: To compare the
performance of graduates of foreign medical schools and last year medical
students of the University of Chile in the same internal medicine OSCE. MATERIAL
AND METHODS: Seventy-seven last year medical students and thirty-three graduates
of foreign medical schools participated in the same Internal Medicine OSCE, but
in different moments. At the end of the examination, graduates of foreign medical
schools answered a questionnaire about their prior experience with OSCEs and
about their perception about this type of examination. RESULTS: The performance
of graduates of foreign medical schools was lower than those of our last year
medical students in four of the eight stations of the examination. Graduates of
foreign medical schools considered the examination objective, fair, and that it
assessed skills adequately and that the degree difficulty was homogeneous for all
examinees. CONCLUSIONS: The possibility of obtaining comparable results in a
transparent process makes the OSCE the assessment tool of choice for title
revalidation of physicians migrating from foreign countries.
PMID- 26436937
TI - [A biographical sketch of Albert Szent-Gyorgyi].
AB - Albert Szent-Gyorgyi was a Hungarian biochemist and physiologist. He identified
the structure and function of vitamin C, naming it as ascorbic acid. His research
on cellular respiration and oxidation provided the basis for Krebs' citric acid
cycle. He was awarded the Nobel Prize in 1937. With his collaborators, he
discovered the biochemical basis of muscle contractility, isolating the basic
proteins, giving them the name myosin and actin. Later on, he worked on the
theory of carcinogenesis, linked to electron movements. He was one of the first
researchers to describe the connection between free radicals and cancer. He lived
a long, very complete life, defending always his opinion and freedom.
PMID- 26436938
TI - [Invasive disease due to Streptococcus pyogenes in a patient with A H1N1
influenza infection. Report of one case].
AB - Bacterial superinfection is a known complication among patients affected by viral
respiratory tract infections. Streptococcus pyogenes, a major bacterial agent
involved in acute tonsillopharyngitis, skin and soft tissue infections, was
reported as a co-infecting microorganism during the 2009 A H1N1 influenza
pandemic. We report a 65-year-old male patient who evolved with multifocal
pneumonia and multiple organ failure with a fatal outcome. Influenza A H1N1 was
detected by a polymerase chain reaction-based technique from a tracheal aspirate
sample. S. pyogenes was identified by a rapid test from a nasopharyngeal sample
and isolated afterwards from a positive blood culture.
PMID- 26436939
TI - [Intravascular lymphoma: Report of one case].
AB - Intravascular lymphoma is a rare subtype of extranodal diffuse large B-cell
lymphoma characterized by clonal proliferation of lymphocytes inside of small and
medium caliber vessels. Its incidence is estimated at one case per million. The
clinical picture is very variable, but frequently has skin and central nervous
system involvement. It is diagnosed by demonstrating pathological blood vessel
infiltration by lymphoma cells. We report a 44 years old male presenting with
fever, malaise and erythematous lesions in the abdominal wall. An abdominal wall
biopsy showed dilated vascular vessels with atypical cells in their lumen,
compatible with large B-cell intravascular lymphoma. He was treated with
rituximab, cyclophosphamide, adriamycin, vincristine and prednisone and an
autologous hematopoietic stem cell transplantation, achieving a complete
remission that has lasted two years.
PMID- 26436940
TI - Type I persistent proatlantal artery associated with fusiform subclavian artery
aneurysm: Report of one case.
AB - We report a 61 years old male presenting with a right cerebral infarction, along
with a type I persistent left proatlantal artery (PA), which is a form of
primitive carotid-basilar anastomosis. The patient had an absence of the
ipsilateral vertebral artery (VA) and hypoplasia of the contralateral VA, while
the basilar artery was supplied by the PA. Other vascular anomalies present were
a fusiform aneurysm of the right subclavian artery, and an A1 segment aplasia of
the hypoplastic anterior right cerebral artery, which originated from the
anterior communicating artery. To our knowledge these anomalies were not
described previously.
PMID- 26436941
TI - [Recurrence of Tako-Tsubo syndrome. Case report].
PMID- 26436942
TI - [The BRAIN initiative: Is it only studied in computers?].
PMID- 26436943
TI - [Sedentary behaviour and physical inactivity is not the same!: An update of
concepts oriented towards the prescription of physical exercise for health].
PMID- 26436945
TI - Impact of neonicotinoid seed treatment of cotton on the cotton leafhopper,
Amrasca devastans (Hemiptera: Cicadellidae), and its natural enemies.
AB - BACKGROUND: Neonicotinoid seed treatments suppress populations of pest insects
efficiently and can enhance crop growth, but they may have negative effects on
beneficial arthropods. We evaluated the effects of either imidacloprid or
thiamethoxam on the abundances of a sucking pest, the cotton leafhopper (Amrasca
devastans), and its arthropod predators under field conditions. We also evaluated
the impact of seed treatment on transgenic cotton plant growth, with pests and
natural enemies present or absent. RESULTS: Imidacloprid and thiamethoxam reduced
pest abundance, with greater effects when dosages were higher. Treatment at
recommended doses delayed the pest in reaching the economic damage threshold by
around 10-15 days (thiamethoxam) and 20 days (imidacloprid). Recommended doses
also enhanced plant growth under all tested conditions; growth is affected
directly as well as via pest suppression. Neonicotinoid applications reduced
abundance of beneficial arthropods, with lower populations after higher doses,
but negative effects of imidacloprid were not apparent unless the manufacturer
recommended dose was exceeded. CONCLUSION: Imidacloprid applied at the
recommended dose of 5 g kg(-1) seed is effective against A. devastans and appears
to be safer than thiamethoxam for natural enemies, and also enhances plant growth
directly. We caution, however, that possible sublethal negative effects on
individual beneficial arthropods were not evaluated. (c) 2015 Society of Chemical
Industry.
PMID- 26436944
TI - Comparative Proteomic Analysis of Aminoglycosides Resistant and Susceptible
Mycobacterium tuberculosis Clinical Isolates for Exploring Potential Drug
Targets.
AB - Aminoglycosides, amikacin (AK) and kanamycin (KM) are second line anti
tuberculosis drugs used to treat tuberculosis (TB) and resistance to them affects
the treatment. Membrane and membrane associated proteins have an anticipated role
in biological processes and pathogenesis and are potential targets for the
development of new diagnostics/vaccine/therapeutics. In this study we compared
membrane and membrane associated proteins of AK and KM resistant and susceptible
Mycobacterium tuberculosis isolates by 2DE coupled with MALDI-TOF/TOF-MS and
bioinformatic tools. Twelve proteins were found to have increased intensities
(PDQuest Advanced Software) in resistant isolates and were identified as ATP
synthase subunit alpha (Rv1308), Trigger factor (Rv2462c), Dihydrolipoyl
dehydrogenase (Rv0462), Elongation factor Tu (Rv0685), Transcriptional regulator
MoxR1(Rv1479), Universal stress protein (Rv2005c), 35kDa hypothetical protein
(Rv2744c), Proteasome subunit alpha (Rv2109c), Putative short-chain type
dehydrogenase/reductase (Rv0148), Bacterioferritin (Rv1876), Ferritin (Rv3841)
and Alpha-crystallin/HspX (Rv2031c). Among these Rv2005c, Rv2744c and Rv0148 are
proteins with unknown functions. Docking showed that both drugs bind to the
conserved domain (Usp, PspA and SDR domain) of these hypothetical proteins and
GPS-PUP predicted potential pupylation sites within them. Increased intensities
of these proteins and proteasome subunit alpha might not only be
neutralized/modulated the drug molecules but also involved in protein turnover to
overcome the AK and KM resistance. Besides that Rv1876, Rv3841 and Rv0685 were
found to be associated with iron regulation signifying the role of iron in
resistance. Further research is needed to explore how these potential protein
targets contribute to resistance of AK and KM.
PMID- 26436946
TI - Controlling the Nanoscale Rotational Behaviors of Nanoparticles on the Cell
Membranes: A Computational Model.
AB - Nanoparticles prefer to bind to a membrane with a surface coated by short or
rigid ligands, as shown by computer simulations. To realize such a preferred
configuration, the nanoparticle can spontaneously spin itself on the membrane
surface, no matter what its initial orientation is.
PMID- 26436947
TI - Charge Separation and Catalytic Activity of Fe3 O4 @Ag "Nanospheres".
AB - Nanospheres of Ag-coated Fe3 O4 were successfully synthesized and characterized.
Photocatalytic properties of Fe3 O4 @Ag composites have been investigated using
steady-state studies and laser pulse excitations. Accumulation of the electrons
in the Ag shell was detected from the shift in the surface plasmon band from 430
to 405 nm, which was discharged when an electron acceptor such as O2 , Thionine
(TH) or C60 was introduced into the system. Charge equilibration with redox
couple such as C60 (?-) /C60 indicated the ability of these core-shell structures
to carry out photocatalytic reduction reactions. As well, outer Ag layer could
boost charge separation in magnetic core through dual effects of Schottky
junction and localized surface plasmonic resonance (LSPR)-powered band gap
breaking effect under sunlight irradiation; resulted in higher photocatalytic
degradation of diphenylamine (DPA). The maximum photocatalytic degradation rate
was achieved at optimum amount of Ag-NP loading to products. Adsorption studies
confirmed that degradation of DPA dominantly occurred in solution. Moderately
renewability of the nanocatalysts under sunlight was due to oxidation and
dissolution of the outer Ag layer.
PMID- 26436948
TI - Development and Characterization of Nanoembedded Microparticles for Pulmonary
Delivery of Antitubercular Drugs against Experimental Tuberculosis.
AB - The foremost objective of the present research study was to develop and evaluate
the potential of rifampicin (RIF) and isoniazid (INH) loaded spray dried
nanoembedded microparticles against experimental tuberculosis (TB). In this
study, RIF-INH loaded various formulations (chitosan, guar gum, mannan, and guar
gum coated chitosan) were prepared by spray drying and characterized on the basis
of in vitro as well as in vivo studies. Results showed that guar gum spray dried
particles showed uniform size distribution with smooth surface as compare to
mannan formulations. Guar gum batches exhibited excellent flow ability attributed
to their optimum moisture content and uniform size distribution. The drug release
showed the biphasic pattern of release, i.e., initial burst followed by a
sustained release pattern. The preferential uptake of guar gum coated
formulations suggested the presence and selective uptake capability of mannose
moiety to the specific cell surface of macrophages. In vivo lung distribution
study showed that guar gum coated chitosan (GCNP) batches demonstrated prolonged
residence at the target site and thereby improve the therapeutic utility of drug
with a significant reduction in systemic toxicity. Optimized drug loaded GCNP
formulation has resulted in almost 5-fold reduction of the number of bacilli as
compared to control group. Histopathology study also demonstrated that none of
the treated groups show any evidence of lung tissue abnormality. Hence, GCNPs
could be a promising carrier for selective delivery of antitubercular drugs to
alveolar macrophages with the interception of minimal side effects, for efficient
management of TB.
PMID- 26436949
TI - Incidence and management of myelosuppression in patients with chronic- and
accelerated-phase chronic myeloid leukemia treated with omacetaxine
mepesuccinate.
AB - Omacetaxine mepesuccinate (Synribo) is an inhibitor of protein synthesis
indicated for the treatment of patients with chronic- or accelerated-phase
chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more
tyrosine kinase inhibitors. Myelosuppression is the most common and clinically
significant toxicity experienced by patients treated with omacetaxine. Here, we
further examine the patterns of hematologic toxicity observed in clinical trials
and describe the approach to management as well as resolution of events.
Omacetaxine-related myelosuppression typically occurs more frequently during
induction cycles. In general, the myelosuppression observed with omacetaxine
treatment is manageable and reversible, and long-term administration is feasible.
Careful monitoring, dose delays and reduction in administration days, and
appropriate supportive care are critical for successful management of hematologic
toxicity. Concerns regarding myelosuppression, observed with many cancer
treatments, should not prevent eligible patients from receiving omacetaxine,
particularly CML patients with unsatisfactory responses to multiple lines of
prior treatment.
PMID- 26436950
TI - Regulation of triple-negative breast cancer cell metastasis by the tumor
suppressor liver kinase B1.
AB - Liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), has
been identified as a tumor suppressor in many cancers including breast. Low LKB1
expression has been associated with poor prognosis of breast cancer patients, and
we report here a significant association between loss of LKB1 expression and
reduced patient survival specifically in the basal subtype of breast cancer.
Owing to the aggressive nature of the basal subtype as evidenced by high
incidences of metastasis, the purpose of this study was to determine if LKB1
expression could regulate the invasive and metastatic properties of this specific
breast cancer subtype. Induction of LKB1 expression in basal-like breast cancer
(BLBC)/triple-negative breast cancer cell lines, MDA-MB-231 and BT-549, inhibited
invasiveness in vitro and lung metastatic burden in an orthotopic xenograft
model. Further analysis of BLBC cells overexpressing LKB1 by unbiased whole
transcriptomics (RNA-sequencing) revealed striking regulation of metastasis
associated pathways, including cell adhesion, extracellular matrix remodeling,
and epithelial-to-mesenchymal transition (EMT). In addition, LKB1 overexpression
inhibited EMT-associated genes (CDH2, Vimentin, Twist) and induced the epithelial
cell marker CDH1, indicating reversal of the EMT phenotype in the MDA-MB-231
cells. We further demonstrated marked inhibition of matrix metalloproteinase 1
expression and activity via regulation of c-Jun through inhibition of p38
signaling in LKB1-expressing cells. Taken together, these data support future
development of LKB1 inducing therapeutics for the suppression of invasion and
metastasis of BLBC.
PMID- 26436951
TI - PIK3CA mutations can initiate pancreatic tumorigenesis and are targetable with
PI3K inhibitors.
AB - Aberrations in the phosphoinositide 3-kinase (PI3K) signaling pathway have a key
role in the pathogenesis of numerous cancers by altering cell growth, metabolism,
proliferation and apoptosis. Interest in targeting the PI3K signaling cascade
continues, as new agents are being clinically evaluated. PIK3CA mutations result
in a constitutively active PI3K and are present in a subset of pancreatic
cancers. Here we examine mutant PIK3CA-mediated pancreatic tumorigenesis and the
response of PIK3CA mutant pancreatic cancers to dual PI3K/mammalian target of
rapamycin (mTOR) inhibition. Two murine models were generated expressing a
constitutively active PI3K within the pancreas. An increase in acinar-to-ductal
metaplasia and pancreatic intraepithelial neoplasms (PanINs) was identified. In
one model these lesions were detected as early as 10 days of age. Invasive
pancreatic ductal adenocarcinoma developed in these mice as early as 20 days of
age. These cancers were highly sensitive to treatment with dual PI3K/mTOR
inhibition. In the second model, PanINs and invasive cancer develop with a
greater latency owing to a lesser degree of PI3K pathway activation in this
murine model. In addition to PI3K pathway activation, increased ERK1/2 signaling
is common in human pancreatic cancers. Phosphorylation of ERK1/2 was also
investigated in these models. Phosphorylation of ERK1/2 is demonstrated in the
pre-neoplastic lesions and invasive cancers. This activation of ERK1/2 is
diminished with dual PI3K/mTOR inhibition. In summary, PIK3CA mutations can
initiate pancreatic tumorigenesis and these cancers are particularly sensitive to
dual PI3K/mTOR inhibition. Future studies of PI3K pathway inhibitors for patients
with PIK3CA mutant pancreatic cancers are warranted.
PMID- 26436952
TI - MiR expression profiles of paired primary colorectal cancer and metastases by
next-generation sequencing.
AB - MicroRNAs (miRs) have been recognized as promising biomarkers. It is unknown to
what extent tumor-derived miRs are differentially expressed between primary
colorectal cancers (pCRCs) and metastatic lesions, and to what extent the
expression profiles of tumor tissue differ from the surrounding normal tissue.
Next-generation sequencing (NGS) of 220 fresh-frozen samples, including paired
primary and metastatic tumor tissue and non-tumorous tissue from 38 patients,
revealed expression of 2245 known unique mature miRs and 515 novel candidate
miRs. Unsupervised clustering of miR expression profiles of pCRC tissue with
paired metastases did not separate the two entities, whereas unsupervised
clustering of miR expression profiles of pCRC with normal colorectal mucosa
demonstrated complete separation of the tumor samples from their paired normal
mucosa. Two hundred and twenty-two miRs differentiated both pCRC and metastases
from normal tissue samples (false discovery rate (FDR) <0.05). The highest
expressed tumor-specific miRs were miR-21 and miR-92a, both previously described
to be involved in CRC with potential as circulating biomarker for early
detection. Only eight miRs, 0.5% of the analysed miR transcriptome, were
differentially expressed between pCRC and the corresponding metastases (FDR
<0.1), consisting of five known miRs (miR-320b, miR-320d, miR-3117, miR-1246 and
miR-663b) and three novel candidate miRs (chr 1-2552-5p, chr 8-20656-5p and chr
10-25333-3p). These results indicate that previously unrecognized candidate miRs
expressed in advanced CRC were identified using NGS. In addition, miR expression
profiles of pCRC and metastatic lesions are highly comparable and may be of
similar predictive value for prognosis or response to treatment in patients with
advanced CRC.
PMID- 26436953
TI - Using community-based participatory research in patient-centered outcomes
research to address health disparities in under-represented communities.
AB - The emergence of patient-centered outcomes research (PCOR) has created a paradigm
shift in the way health outcomes research is designed, conducted and
disseminated. While PCOR expands the potential for patients to play a key
advisory role in every aspect of the research process, community-based
participatory research (CBPR) has long provided this opportunity for engaging
communities in research. CBPR is an excellent tool for achieving PCOR goals of
improving the health of all people by providing them with evidence-based
information for making informed healthcare decisions. We propose ways by which
PCOR can effectively use CBPR principles to engage patients in general, and
specifically patients from underserved communities. The hope is that this will
help to reduce and eventually eliminate health disparities.
PMID- 26436955
TI - Disappearing bone disease of the humerus and the cervico-thoracic spine: a case
report with 42-year follow-up.
AB - BACKGROUND CONTEXT: Disappearing bone disease (DBD) is a rare idiopathic
musculoskeletal disorder that is distinguished by bone resorption without bone
formation, vascular or lymphatic vessel proliferation, and soft-tissue swelling.
Long-term follow-up of a patient with DBD has rarely been reported in the
literature. PURPOSE: The following is a case report of a female patient with DBD
of the humerus and the spine who was followed for 42 years, documenting the
progression of the disease and outcomes. STUDY DESIGN: Case report. METHODS: A
review of the medical records since the time of initial hospital admission
throughout follow-up was performed. RESULTS: A female patient was first seen at
our institution at the age of 14. She later developed DBD of the humerus and the
spine. The initial difficulty encountered was reaching the diagnosis, and later
on with management of the patient as the disease progressed. The case was
complicated by syrinx and arachnoid cyst formation, which caused neurologic
changes leading to tetraplegia and shunt infection. The patient's inability to
form a solid fusion mass led to repeated implant loosening and progressive
deformity despite efforts made to stabilize both the humerus and the spine. The
treatment modalities used were oral bisphosphonates, rhBMP, repeated surgeries,
and instrumentation with adjunct bone graft and substitutes. At the age of 56
years, the patient died because of septicemia secondary to urinary tract
infection from tetraplegia. CONCLUSIONS: To our knowledge, this is the first
report documenting a 42-year follow-up of a patient with DBD of the humerus and
the spine. Our report showed that DBD greatly affects the quality of life of the
patient. Close follow-up, a multidisciplinary approach, and supportive care are
stressed when managing patients with DBD.
PMID- 26436956
TI - Is dysphagia an orthopedic problem?--Yes, it could be!
PMID- 26436954
TI - Transcriptome profiling reveals divergent expression shifts in brown and white
adipose tissue from long-lived GHRKO mice.
AB - Mice lacking the growth hormone receptor (GHRKO) exhibit improved lifespan and
healthspan due to loss of growth hormone signaling. Both the distribution and
activity of brown and white adipose tissue (BAT and WAT) are altered in GHRKO
mice, but the contribution of each tissue to age-related phenotypes has remained
unclear. We therefore used whole-genome microarrays to evaluate transcriptional
differences in BAT and WAT depots between GHRKO and normal littermates at six
months of age. Our findings reveal a unique BAT transcriptome as well as
distinctive responses of BAT to Ghr ablation. BAT from GHRKO mice exhibited
elevated expression of genes associated with mitochondria and metabolism, along
with reduced expression of genes expressed by monocyte-derived cells (dendritic
cells [DC] and macrophages). Largely the opposite was observed in WAT, with
increased expression of DC-expressed genes and reduced expression of genes
associated with metabolism, cellular respiration and the mitochondrial inner
envelope. These findings demonstrate divergent response patterns of BAT and WAT
to loss of GH signaling in GHRKO mice. These patterns suggest both BAT and WAT
contribute in different ways to phenotypes in GHRKO mice, with Ghr ablation
blunting inflammation in BAT as well as cellular metabolism and mitochondrial
biogenesis in WAT.
PMID- 26436957
TI - Radiofrequency ablation of a rare pathology: vertebral intraosseous lipoma.
PMID- 26436958
TI - The complete mitochondrial genome sequence of Nemateleotris decora (gobiiformes,
gobiidae).
AB - We determined the mitochondrial genome (mitogenome) sequence of Nemateleotris
decora by using a long polymerase chain reaction (PCR) method and next-generation
sequence (NGS) technology. The total length of N. decora mitogenome is 16 502 bp,
consisting of 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs
genes, and a non-coding control region. The overall base composition of N. decora
is 25.22% for A, 25.90% for T, 30.69% for G, and 18.19% for C. Our results showed
the complete mitogenome is a good marker for the phylogenetic study.
PMID- 26436959
TI - Workplace interventions to prevent work disability in workers on sick leave.
AB - BACKGROUND: Work disability has serious consequences for individuals as well as
society. It is possible to facilitate resumption of work by reducing barriers to
return to work (RTW) and promoting collaboration with key stakeholders. This
review was first published in 2009 and has now been updated to include studies
published up to February 2015. OBJECTIVES: To determine the effectiveness of
workplace interventions in preventing work disability among sick-listed workers,
when compared to usual care or clinical interventions. SEARCH METHODS: We
searched the Cochrane Work Trials Register, the Cochrane Central Register of
Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO databases on 2
February 2015. SELECTION CRITERIA: We included randomised controlled trials
(RCTs) of workplace interventions that aimed to improve RTW for disabled workers.
We only included studies where RTW or conversely sickness absence was reported as
a continuous outcome. DATA COLLECTION AND ANALYSIS: Two review authors
independently extracted data and assessed risk of bias of the studies. We
performed meta-analysis where possible, and we assessed the quality of evidence
according to GRADE criteria. We used standard methodological procedures expected
by Cochrane. MAIN RESULTS: We included 14 RCTs with 1897 workers. Eight studies
included workers with musculoskeletal disorders, five workers with mental health
problems, and one workers with cancer. We judged six studies to have low risk of
bias for the outcome sickness absence.Workplace interventions significantly
improved time until first RTW compared to usual care, moderate-quality evidence
(hazard ratio (HR) 1.55, 95% confidence interval (CI) 1.20 to 2.01). Workplace
interventions did not considerably reduce time to lasting RTW compared to usual
care, very low-quality evidence (HR 1.07, 95% CI 0.72 to 1.57). The effect on
cumulative duration of sickness absence showed a mean difference of -33.33 (95%
CI -49.54 to -17.12), favouring the workplace intervention, high-quality
evidence. One study assessed recurrences of sick leave, and favoured usual care,
moderate-quality evidence (HR 0.42, 95% CI 0.21 to 0.82). Overall, the
effectiveness of workplace interventions on work disability showed varying
results.In subgroup analyses, we found that workplace interventions reduced time
to first and lasting RTW among workers with musculoskeletal disorders more than
usual care (HR 1.44, 95% CI 1.15 to 1.82 and HR 1.77, 95% CI 1.37 to 2.29,
respectively; both moderate-quality evidence). In studies of workers with
musculoskeletal disorders, pain also improved (standardised mean difference (SMD)
-0.26, 95% CI -0.47 to -0.06), as well as functional status (SMD -0.33, 95% CI
0.58 to -0.08). In studies of workers with mental health problems, there was a
significant improvement in time until first RTW (HR 2.64, 95% CI 1.41 to 4.95),
but no considerable reduction in lasting RTW (HR 0.79, 95% CI 0.54 to 1.17). One
study of workers with cancer did not find a considerable reduction in lasting RTW
(HR 0.88, 95% CI 0.53 to 1.47).In another subgroup analysis, we did not find
evidence that offering a workplace intervention in combination with a cognitive
behavioural intervention (HR 1.93, 95% CI 1.27 to 2.93) is considerably more
effective than offering a workplace intervention alone (HR 1.35, 95% CI 1.01 to
1.82, test for subgroup differences P = 0.17).Workplace interventions did not
considerably reduce time until first RTW compared with a clinical intervention in
workers with mental health problems in one study (HR 2.65, 95% CI 1.42 to 4.95,
very low-quality evidence). AUTHORS' CONCLUSIONS: We found moderate-quality
evidence that workplace interventions reduce time to first RTW, high-quality
evidence that workplace interventions reduce cumulative duration of sickness
absence, very low-quality evidence that workplace interventions reduce time to
lasting RTW, and moderate-quality evidence that workplace interventions increase
recurrences of sick leave. Overall, the effectiveness of workplace interventions
on work disability showed varying results. Workplace interventions reduce time to
RTW and improve pain and functional status in workers with musculoskeletal
disorders. We found no evidence of a considerable effect of workplace
interventions on time to RTW in workers with mental health problems or cancer.We
found moderate-quality evidence to support workplace interventions for workers
with musculoskeletal disorders. The quality of the evidence on the effectiveness
of workplace interventions for workers with mental health problems and cancer is
low, and results do not show an effect of workplace interventions for these
workers. Future research should expand the range of health conditions evaluated
with high-quality studies.
PMID- 26436960
TI - Self-reported symptoms and risk factors for digital ischaemia among international
world-class beach volleyball players.
AB - The prevalence of ischaemia-related symptoms is remarkably high among elite
indoor volleyball players. Since the exposure to sport-specific demands may be
higher in beach volleyball compared to indoor volleyball, the aim of this study
was to assess the prevalence of ischaemia-related symptoms and associated risk
factors among world-class beach volleyball players. Therefore, a questionnaire
survey was performed among beach volleyball players active during the 2013 Grand
Slam Beach Volleyball in the Netherlands. In total, 60 of the 128 beach
volleyball players (47%) participated: 26 males and 34 females from 17 countries.
The self-reported prevalence of cold or blue or pale digits in the dominant hand
during or immediately after practice or competition was 38% (n = 23). Two risk
factors were independently associated with symptoms of blue or pale digits: more
than 14 years playing volleyball (odds ratio (OR) 4.42, 90% confidence interval
(90% CI) 1.30-15.07) and sex (female) (OR 4.62, 90% CI 1.15-18.57). In
conclusion, the prevalence of symptoms associated with digital ischaemia is high
among international world-class beach volleyball players. Female sex and the
length of the volleyball career were independently associated with an increased
risk of ischaemia-related symptoms. The high prevalence of these seemingly
innocuous symptoms and possible associated risk factors warrant regular
monitoring since early detection can potentially prevent thromboembolic
complications and irreversible tissue damage.
PMID- 26436961
TI - VBN-based nomograms provide critical voiding parameters which can be used for
invasive or non-invasive flow interpretation of women at risk of obstruction over
time.
AB - AIMS: To design a simple office-based method to evaluate characteristic
parameters from free uroflowmetries (FF) or pressure flow studies (PFs). This
method can be applied by any physician to any recording, for instance in the
follow-up of women at risk of developing outflow obstruction over time after
surgical interventions. METHOD: Using pressure-flow studies (PFs), a reliable
evaluation of urethral obstruction (U) and detrusor contractility (k) parameters
could be obtained from the maximum flow rate and detrusor pressure at maximum
flow rate. Nomograms for these parameters were derived from theoretical
computations using the VBN model. Then, to allow an evaluation of the real
urethral obstruction, a protocol was designed incorporating FF data in the follow
up of women suspected of urethral obstruction. RESULTS: Two nomograms were
obtained: (1) A urethral obstruction nomogram allowing to define a Woman
Obstruction Index (WOI = pdet.Qmax - 0.5*Qmax ) which has the same structure than
the A-G number in men. (2) A detrusor contractility nomogram which was
generalized to all initial bladder volumes. The curves were fitted by algebraic
equations easily programmable on any handheld device. CONCLUSION: Using a
mathematical model of micturition and data extracted from PFs, two nomograms on
urethral obstruction and detrusor contractility were designed. This tool offers a
rapid and practical method for the clinician to follow women at risk of
obstruction over time. Its applications will be the purpose of further studies.
Neurourol. Urodynam. 36:37-42, 2017. (c) 2015 Wiley Periodicals, Inc.
PMID- 26436962
TI - Use of Whole-Exome Sequencing for Diagnosis of Limb-Girdle Muscular Dystrophy:
Outcomes and Lessons Learned.
AB - IMPORTANCE: To our knowledge, the efficacy of transferring next-generation
sequencing from a research setting to neuromuscular clinics has never been
evaluated. OBJECTIVE: To translate whole-exome sequencing (WES) to clinical
practice for the genetic diagnosis of a large cohort of patients with limb-girdle
muscular dystrophy (LGMD) for whom protein-based analyses and targeted Sanger
sequencing failed to identify the genetic cause of their disorder. DESIGN,
SETTING, AND PARTICIPANTS: We performed WES on 60 families with LGMDs (100
exomes). Data analysis was performed between January 6 and December 19, 2014,
using the xBrowse bioinformatics interface (Broad Institute). Patients with LGMD
were ascertained retrospectively through the Institute for Neuroscience and
Muscle Research Biospecimen Bank between 2006 and 2014. Enrolled patients had
been extensively investigated via protein studies and candidate gene sequencing
and remained undiagnosed. Patients presented with more than 2 years of muscle
weakness and with dystrophic or myopathic changes present in muscle biopsy
specimens. MAIN OUTCOMES AND MEASURES: The diagnostic rate of LGMD in Australia
and the relative frequencies of the different LGMD subtypes. Our central goals
were to improve the genetic diagnosis of LGMD, investigate whether the WES
platform provides adequate coverage of known LGMD-related genes, and identify new
LGMD-related genes. RESULTS: With WES, we identified likely pathogenic mutations
in known myopathy genes for 27 of 60 families. Twelve families had mutations in
known LGMD-related genes. However, 15 families had variants in disease-related
genes not typically associated with LGMD, highlighting the clinical overlap
between LGMD and other myopathies. Common causes of phenotypic overlap were due
to mutations in congenital muscular dystrophy-related genes (4 families) and
collagen myopathy-related genes (4 families). Less common myopathies included
metabolic myopathy (2 families), congenital myasthenic syndrome (DOK7),
congenital myopathy (ACTA1), tubular aggregate myopathy (STIM1), myofibrillar
myopathy (FLNC), and mutation of CHD7, usually associated with the CHARGE
syndrome. Inclusion of family members increased the diagnostic efficacy of WES,
with a diagnostic rate of 60% for "trios" (an affected proband with both parents)
vs 40% for single probands. A follow-up screening of patients whose conditions
were undiagnosed on a targeted neuromuscular disease-related gene panel did not
improve our diagnostic yield. CONCLUSIONS AND RELEVANCE: With WES, we achieved a
diagnostic success rate of 45.0% in our difficult-to-diagnose cohort of patients
with LGMD. We expand the clinical phenotypes associated with known myopathy
genes, and we stress the importance of accurate clinical examination and
histopathological results for interpretation of WES, with many diagnoses
requiring follow-up review and ancillary investigations of biopsy specimens or
serum samples.
PMID- 26436963
TI - Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves.
AB - BACKGROUND: A finding of reduced aortic-valve leaflet motion was noted on
computed tomography (CT) in a patient who had a stroke after transcatheter aortic
valve replacement (TAVR) during an ongoing clinical trial. This finding raised a
concern about possible subclinical leaflet thrombosis and prompted further
investigation. METHODS: We analyzed data obtained from 55 patients in a clinical
trial of TAVR and from two single-center registries that included 132 patients
who were undergoing either TAVR or surgical aortic-valve bioprosthesis
implantation. We obtained four-dimensional, volume-rendered CT scans along with
data on anticoagulation and clinical outcomes (including strokes and transient
ischemic attacks [TIAs]). RESULTS: Reduced leaflet motion was noted on CT in 22
of 55 patients (40%) in the clinical trial and in 17 of 132 patients (13%) in the
two registries. Reduced leaflet motion was detected among patients with multiple
bioprosthesis types, including transcatheter and surgical bioprostheses.
Therapeutic anticoagulation with warfarin, as compared with dual antiplatelet
therapy, was associated with a decreased incidence of reduced leaflet motion (0%
and 55%, respectively, P=0.01 in the clinical trial; and 0% and 29%,
respectively, P=0.04 in the pooled registries). In patients who were reevaluated
with follow-up CT, restoration of leaflet motion was noted in all 11 patients who
were receiving anticoagulation and in 1 of 10 patients who were not receiving
anticoagulation (P<0.001). There was no significant difference in the incidence
of stroke or TIA between patients with reduced leaflet motion and those with
normal leaflet motion in the clinical trial (2 of 22 patients and 0 of 33
patients, respectively; P=0.16), although in the pooled registries, a significant
difference was detected (3 of 17 patients and 1 of 115 patients, respectively;
P=0.007). CONCLUSIONS: Reduced aortic-valve leaflet motion was shown in patients
with bioprosthetic aortic valves. The condition resolved with therapeutic
anticoagulation. The effect of this finding on clinical outcomes including stroke
needs further investigation. (Funded by St. Jude Medical and Cedars-Sinai Heart
Institute; Portico-IDE ClinicalTrials.gov number, NCT02000115; SAVORY registry,
NCT02426307; and RESOLVE registry, NCT02318342.).
PMID- 26436964
TI - Adverse drug reactions in Ghanaian children: review of reports from 2000 to 2012
in VigiBase.
AB - OBJECTIVE: The aim of this article is to describe adverse drug reactions (ADRs)
reported for children aged 0 - 17 years in Ghana. METHODS: Paediatric reports
submitted by the Ghana National Centre for Pharmacovigilance to the World Health
Organisation (WHO) Global ADR database, VigiBase up to December 2012 were
extracted. The data were analysed for number of reports per year, types of
reporters and suspected ADRs and drugs. RESULTS: A total of 343 reports for
children were received during the period. The drug classes most frequently
reported were vaccines (115, 31%), antimalarials (106, 28%) and antibiotics (57,
15%). Of the top 20 individual drugs, 19 were anti-infectives. The most
frequently reported ADRs were injection site infection, fever and rash. There
were 23 deaths reported, and antimalarials were implicated in 12 cases.
CONCLUSIONS: Vaccines, antimalarials and antibiotics are the leading medicines
reported to cause ADRs in Ghanaian children. There was a high mortality rate,
with many of the deaths due to causes explained in the individual case safety
reports.
PMID- 26436965
TI - Psoriasis disease severity affects patient satisfaction with treatment.
AB - BACKGROUND: Patients with psoriasis are often dissatisfied with available
treatments, but contributing factors are not well defined. OBJECTIVE: Examine
relationships between psoriasis severity, patient characteristics, and treatment
satisfaction. METHODS: Patients with psoriasis were classified into mild and
moderate-to-severe groups based on self-reported data. Demographics,
comorbidities, symptoms, and multiple treatment satisfaction outcomes were
compared between groups. Predictors of patient satisfaction with treatment were
examined using linear regression models. RESULTS: The analyses included 773
patients (407 mild; 366 moderate-to-severe). The percentage of patients reporting
satisfaction with treatment was low overall, ranging from 8.6% to 61.7% for the
mild and 13.9% to 49.5% for the moderate-to-severe group. Satisfaction among
biologics users was also low (<=53%; 50% of satisfaction rates <40%). Regression
results consistently showed greater dissatisfaction with current treatment among
moderately to severely affected patients. CONCLUSION: Many psoriasis patients
were dissatisfied with their treatment; moderate-to-severe patients expressed
significantly less satisfaction than mild patients.
PMID- 26436966
TI - Beta blocker treatment for infantile hemangiomas.
AB - Infantile hemangiomas (IH) are common childhood vascular tumors. Treatment of IH
has undergone rapid change in recent years. Since 2008, oral propranolol has
been used to treat complicated IH and has proven superior to previously used
therapies. More recently, the efficacy of other systemic beta blockers,
specifically atenolol and nadolol, has been reported. In addition, topical
timolol solution has been effective for treatment of smaller, more superficial
IH. The purpose of this article is to review the current literature of beta
blocker therapy for IH.
PMID- 26436967
TI - Successful treatment of psoriasis with ustekinumab in patients with multiple
sclerosis.
AB - Psoriasis is a chronic inflammatory disease, evolving from a complex interplay of
genetic and environmental factors. In the recent years, we have seen much
progress in understanding the immunopathogenesis of psoriasis, paving the way for
new therapies with biologics. Currently, the most commonly used biologics in
psoriasis are TNF inhibitors etanercept, infliximab and adalimumab, and the IL
12/23 inhibitor ustekinumab. As TNF inhibitors are contraindicated in patients
with multiple sclerosis, ustekinumab remained the only biologic available for
these patient before the recent approval of Secukinumab, an IL-17A inhibitor.
Herein we report two patients with multiple sclerosis and comorbid psoriasis
successfully treated with ustekinumab without progression of their multiple
sclerosis. Our cases demonstrate that ustekinumab is a reasonably safe choice in
this patient population. We also briefly reviewed new therapies currently under
investigation, which will undoubtedly further expand our armamentarium for the
treatment of psoriasis in patients with neuromuscular diseases.
PMID- 26436968
TI - Acquired cutis laxa associated with cutaneous mastocytosis.
AB - Cutis laxa is characterized by dramatic wrinkling of skin that is lacking in
elasticity due to inherent defects in dermal elastic fibers. Cutis laxa can be
caused by genetic and metabolic disorders. It can also be acquired, possibly
resulting from inflammatory processes with destruction of elastic fibers. This
report describes a 26-year old woman who developed acquired cutis laxa and
cutaneous mastocytosis leading to premature aging. She represents a unique co
occurrence of these two separate disease entities. To our knowledge, there has
been only one published case report of acquired cutis laxa occurring in
association with urticaria pigmentosa in a 4-year old girl. Our case would be a
second case that exhibits the coexistence of these two disorders in an adult
female.
PMID- 26436969
TI - Alopecia as the Presenting Symptom of Syphilis.
AB - Alopecia can be one of the many symptoms of secondary syphilis and the clinical
presentations include essential syphilitic alopecia or symptomatic syphilitic
alopecia. In this report, we present a case of a patient with essential
syphilitic alopecia whose sole presenting symptom of syphilis was alopecia.
Despite an initial negative rapid plasma reagin (RPR) test, he was ultimately
found to have syphilis on scalp biopsy. His alopecia improved following treatment
with benzathine penicillin. This presentation serves as a reminder to clinicians
to be cognizant of alopecia as a presenting sign of syphilis. A review of the
specificity and sensitivity of the typical tests used for the diagnosis is
presented.
PMID- 26436970
TI - Elevated levels of antibodies against phosphatidylserine/prothrombin complex
and/or cardiolipin associated with infection and recurrent purpura in a child: a
forme fruste of antiphospholipid syndrome?
AB - Antiphospholipid syndrome is an autoimmune disorder characterized by the
occurrence of venous and arterial thrombosis, as well as morbidity in pregnancy,
in the presence of anti-phospholipid antibodies. The diagnosis of
antiphospholipid syndrome is usually established based on clinical and laboratory
findings by strictly following the 2006 Sapporo classification. However, the
diagnosis remains challenging owing to the ongoing debates on the serological
criteria. We report a case we describe as forme fruste antiphospholipid syndrome
in which these criteria were not fulfilled. Purpura appeared repeatedly in a
female infant starting from the age of 6 months and following episodes of upper
respiratory infections and vaccinations. The levels of anti-cardiolipin IgG
antibodies and anti-phosphatidylserine/prothrombin complex antibodies were
elevated in accordance with these events. Histopathological evaluation revealed
multiple small vessel thrombi in the dermis and adipose tissue. After 2 weeks of
treatment with aspirin and heparin, the cutaneous symptoms subsided. Infection
has long been associated with antiphospholipid syndrome, and anti
phosphatidylserine/prothrombin antibodies are considered a new marker for the
diagnosis of antiphospholipid syndrome. Forme fruste antiphospholipid syndrome
should be considered even if the antiphospholipid syndrome diagnostic criteria
are not completely fulfilled, especially in the presence of elevated levels of
anti-phosphatidylserine/prothrombin antibodies and known preceding infections.
PMID- 26436971
TI - A case of hair re-pigmentation from a scalp melanoma.
AB - Hair re-pigmentation in adults is a rare phenomenon. We describe a 58-year-old
woman who developed hair re-pigmentation on her vertex scalp as a marker of
underlying melanoma. Histopathology revealed a nodular melanoma that was
surrounding but not invading follicular epithelium. To our knowledge, there have
only been 4 other previously published cases describing hair re-pigmentation in
the setting of scalp melanoma. Focal hair re-pigmentation in adults should prompt
a thorough evaluation for an underlying melanoma.
PMID- 26436972
TI - Linear acral pseudolymphomatous angiokeratoma of children with associated nail
dystrophy.
AB - Acral pseudolymphomatous angiokeratoma of children (APACHE) is a rare entity that
typically occurs on the extremities of young females. Although linear arrangement
of cutaneous lesions has been rarely reported, accompanying nail dystrophy has
not been linked with this condition to our knowledge. We describe a case of
linearly-oriented infiltrative papules and nodules on the index finger of a young
female with associated onychodystrophy. Histology demonstrated a heavy
lymphocytic infiltrate with plasma cells and proliferation of blood vessels
consistent with APACHE. Our case is unique given the linear array of cutaneous
lesions and associated nail dystrophy.
PMID- 26436973
TI - "Cyrano nose" associated with hepatic hemangiomas successfully treated with
propranolol.
AB - Hemangioma of the nasal tip is commonly described as "Cyrano nose" and his
treatment is extremely difficult because of its location and possible severe
aesthetic complications like definitive nasal deformation. We describe a patient
who presented at two months of age with a "Cyrano nose" associated with multiple
hepatic and cutaneous hemangiomas, which completely resolved after therapy with
propranolol. Treatment was well tolerated and aesthetic result was excellent.
PMID- 26436974
TI - Blue rubber bleb nevus syndrome: a rare multisystem affliction.
AB - About 200 cases of blue rubber bleb nevus syndrome (BRBNS) have been reported in
the literature. The disorder affects both sexes equally and the occurrence is
mostly sporadic except for a few reports of cases with autosomal dominant
inheritance pattern. Herein we report an 11-year-old girl with progressive BRBNS
and onset at 5 years of age.
PMID- 26436975
TI - A case of acanthosis nigricans coexisting with mycosis fungoides.
AB - Acanthosis nigricans maligna (ANM) is a paraneoplastic phenomenon most commonly
associated with visceral adenocarcinoma, in particular, gastric adenocarcinoma.
Clinically, AMN is characterized by rapidly progressive symmetrical skin
thickening and hyperpigmentation of the intertriginous areas with peripheral
acrochorda. The diagnosis is made by a detailed medical work-up for occult
malignancies with particular emphasis on endocrinological diseases. We report a
67-year-old man that presented clinically with acanthosis nigricans, in which a
subsequent diagnosis of mycosis fungoides was made.
PMID- 26436976
TI - [Not Available].
AB - Graham-Little-Piccardi-Lassueur syndrome is a rare lichenoid dermatosis. It is
characterized by the triad of scarring alopecia of the scalp, alopecia of the
axilla and or groin, and keratotic follicular papules of the body. The present
paper reports on two cases affecting young women. Histopathological findings
suggest the disorder represents a generalized form of lichen planus follicularis.
PMID- 26436977
TI - Histiocytoid Sweet syndrome treated with azathioprine: a case report.
AB - Histiocytoid Sweet syndrome (HSS) is a rare histologic variation of Sweet
syndrome (SS) predominantly exhibiting mononuclear histiocytoid cells instead of
neutrophils. We report a 22-year-old woman with HSS, who, after minimal
improvement with colchicine and dapsone, had significant improvement of her
cutaneous eruption and systemic symptoms following empiric treatment with
azathioprine. Since azathioprine has historically been known to cause SS, this
case highlights a previously unreported treatment response for the histiocytoid
variant.
PMID- 26436978
TI - A fibrous papule with abundant CD34-immunoreactive ganglion-like multinucleated
giant cells: a case report and review of the literature.
AB - Fibrous papules present clinically as benign, asymptomatic, dome-shaped, flesh
colored papules on the face. Histologically, fibrous papules are characterized by
fibrous stroma with fibroblasts and dilated blood vessels. Multiple variants of
fibrous papules have been reported. Although scattered multinucleated cells in
fibrous papules have been well described, we report a fibrous papule with
abundant multinucleated ganglion-like giant cells that were immunoreactive with
CD34. Recognition of such fibrous papule variants is important to avoid
misdiagnosis as potentially more worrisome and/or aggressive melanocytic, soft
tissue, or neural lesions that may require more aggressive treatment. Indeed,
fibrous papules do not commonly appear on the differential diagnosis for lesions
with multinucleated giant cells or ganglion-like cells and consideration should
be given to their inclusion in the appropriate clinical setting.
PMID- 26436979
TI - Jejunal adenocarcinoma with cutaneous metastasis.
AB - Small bowel adenocarcinoma (SBA) is a rare primary gastrointestinal malignancy.
We present a 60-year old man who developed a cutaneous metastasis of jejunal
adenocarcinoma to his neck. This case highlights the clinicopathologic and
immunophenotypic features of this uncommon cutaneous metastasis.
PMID- 26436980
TI - Unilateral hyperkeratotic plaques along blaschko lines.
AB - Epidermolytic ichthyosis (or epidermolytic hyperkeratosis) classically presents
with erythroderma and increased fragility (blistering) at birth or soon
thereafter. In later life, erythroderma and blistering improve gradually and the
clinical picture is dominated by hyperkeratotic plaques in flexures and around
joints. Linear epidermolytic hyperkeratosis is a unique, uncommon clinical
variant and the absence of erythroderma and blistering are its hallmark. Linear
lesions may be localized or generalized andunilateral or bilateral. Herein we
report a 6-year-old girl with unilateral epidermolytic ichthyosis.
PMID- 26436981
TI - [Not Available].
AB - Pityriasis rotunda disorder of keratinization clinically described as persistent,
large, sharply defined circular patches of ichthyosiform scaling with no
inflammatory changes. Patients with pityriasis rotunda may be classified into one
of two groups, which are based on ethnicity, number of lesions, family history,
and association with systemic diseases. A 45-year-old woman presented with
asymptomatic, sharply-demarcated, round, scaly, hyperpigmented lesions on her leg
that had been present for several years. Our patient did not have systemic
disease or malignancy and so does not fit into groups already described.
PMID- 26436982
TI - Early diagnosis of subungual squamous cell carcinoma of the hallux.
AB - Primary subungual squamous cell carcinoma (SCC) of the toe is rare in the
literature and frequently late or misdiagnosed. Lack of awareness among
physicians of the specific clinical findings, the indolent course of the disease,
and the high prevalence of benign conditions of the nail unit may account for
delays in diagnosis. In addition to difficulties in identifying the true
incidence of this tumor, a standardized therapeutic approach does not currently
exist. We present a case of subungual SCC of the first toe without bone invasion.
The tumor was diagnosed early, treated with conservative surgical excision, and
showed no recurrence or metastasis after 2 years of follow-up.
PMID- 26436983
TI - Monitoring in real time the cytotoxic effect of Clostridium difficile upon the
intestinal epithelial cell line HT29.
AB - The incidence and severity of Clostridium difficile infections (CDI) has been
increased not only among hospitalized patients, but also in healthy individuals
traditionally considered as low risk population. Current treatment of CDI
involves the use of antibiotics to eliminate the pathogen, although recurrent
relapses have also been reported. For this reason, the search of new
antimicrobials is a very active area of research. The strategy to use inhibitors
of toxin's activity has however been less explored in spite of being a promising
option. In this regard, the lack of fast and reliable in vitro screening methods
to search for novel anti-toxin drugs has hampered this approach. The aim of the
current study was to develop a method to monitor in real time the cytotoxicity of
C. difficile upon the human colonocyte-like HT29 line, since epithelial
intestinal cells are the primary targets of the toxins. The label-free, impedance
based RCTA (real time cell analyser) technology was used to follow overtime the
behaviour of HT29 in response to C. difficile LMG21717 producing both A and B
toxins. Results obtained showed that the selection of the medium to grow the
pathogen had a great influence in obtaining toxigenic supernatants, given that
some culture media avoided the release of the toxins. A cytotoxic dose- and time
dependent effect of the supernatant obtained from GAM medium upon HT29 and Caco2
cells was detected. The sigmoid-curve fit of data obtained with HT29 allowed the
calculation of different toxicological parameters, such as EC50 and LOAEL values.
Finally, the modification in the behaviour of HT29 reordered in the RTCA was
correlated with the cell rounding effect, typically induced by these toxins,
visualized by time-lapsed captures using an optical microscope. Therefore, this
RTCA method developed to test cytotoxicity kinetics of C. difficile supernatants
upon IEC could be a valuable in vitro model for the screening of new anti-CDI
agents.
PMID- 26436984
TI - Normal and high eNOS levels are detrimental in both mild and severe cardiac
pressure-overload.
AB - Nitric oxide (NO) produced by endothelial NO synthase (eNOS) exerts beneficial
effects in a variety of cardiovascular disease states. Studies on the benefit of
eNOS activity in pressure-overload cardiac hypertrophy and dysfunction produced
by aortic stenosis are equivocal, which may be due to different expression levels
of eNOS or different severities of pressure-overload. Consequently, we
investigated the effects of eNOS-expression level on cardiac hypertrophy and
dysfunction produced by mild or severe pressure-overload. To unravel the impact
of eNOS on pressure-overload cardiac dysfunction we subjected eNOS deficient,
wildtype and eNOS overexpressing transgenic (eNOS-Tg) mice to 8weeks of mild or
severe transverse aortic constriction (TAC) and studied cardiac geometry and
function at the whole organ and tissue level. In both mild and severe TAC, lack
of eNOS ameliorated, whereas eNOS overexpression aggravated, TAC-induced cardiac
remodeling and dysfunction. Moreover, the detrimental effects of eNOS in severe
TAC were associated with aggravation of TAC-induced NOS-dependent oxidative
stress and by further elevation of eNOS monomer levels, consistent with enhanced
eNOS uncoupling. In the presence of TAC, scavenging of reactive oxygen species
with N-acetylcysteine reduced eNOS S-glutathionylation, eNOS monomer and NOS
dependent superoxide levels in eNOS-Tg mice to wildtype levels. Accordingly, N
acetylcysteine improved cardiac function in eNOS-Tg but not in wildtype mice with
TAC. In conclusion, independent of the severity of TAC, eNOS aggravates cardiac
remodeling and dysfunction, which appears due to TAC-induced eNOS uncoupling and
superoxide production.
PMID- 26436985
TI - Long-chain polyunsaturated fatty acids amend palmitate-induced inflammation and
insulin resistance in mouse C2C12 myotubes.
AB - Intramuscular lipid accumulation results in inflammation, which is correlated
with impaired insulin action in the skeletal muscle, an important organ for
glucose uptake in the body. In this study, we explored the effects of
docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), arachidonic acid (AA),
and long-chain polyunsaturated fatty acids (PUFAs) on palmitic acid (PA)-induced
inflammatory responses and insulin resistance in C2C12 myotubes. The mRNA
expression of the pro-inflammatory cytokines interleukin-6 and tumor necrosis
factor-alpha in PA-treated myotubes was suppressed by these three test long-chain
PUFAs. Moreover, the addition of long-chain PUFAs decreased PA-induced insulin
resistance as evidenced by increases in phosphorylated AKT and glucose uptake. In
PA-treated myotubes, long-chain PUFAs improved glucose transporter 4 expression,
basal glucose uptake without insulin, and the AMP-activated protein kinase
pathway. Of note, the long-chain PUFAs obstructed the effects of PA on the
activation of extracellular-signal-regulated kinase and protein kinase C-theta as
well as nuclear factor-kappaB (NF-kappaB) and activator protein-1. The inhibitory
effect of AA but not of DHA and EPA on PA-induced inflammation and impaired
insulin action was cancelled in C2C12 myotubes transfected with a constitutively
active mutant IkappaB kinase-beta plasmid. These data suggest that long-chain
PUFAs may be useful in the management of PA-induced inflammation and insulin
resistance in myotubes. In addition to the NF-kappaB pathway, other mechanisms
are involved in the health benefits of DHA and EPA in PA-treated myotubes.
PMID- 26436987
TI - Optic Neuropathy Due to Chronic Lymphocytic Leukemia Proven With Optic Nerve
Sheath Biopsy.
AB - Central nervous system involvement from chronic lymphocytic leukemia (CLL) occurs
infrequently, and manifestations include cognitive and cerebellar dysfunction and
cranial nerve palsies. We report a 45-year-old man with CLL believed to be in
clinical remission, who presented with vision loss and bilateral optic disc
edema. His optic neuropathy due to CLL was proven by optic nerve sheath biopsy,
and he experienced visual recovery after treatment with ibrutinib and intrathecal
methotrexate.
PMID- 26436988
TI - Theranos promises a new era of preventive health care - but where's the
physician?
PMID- 26436986
TI - Assessment of Neuromuscular Function Using Percutaneous Electrical Nerve
Stimulation.
AB - Percutaneous electrical nerve stimulation is a non-invasive method commonly used
to evaluate neuromuscular function from brain to muscle (supra-spinal, spinal and
peripheral levels). The present protocol describes how this method can be used to
stimulate the posterior tibial nerve that activates plantar flexor muscles.
Percutaneous electrical nerve stimulation consists of inducing an electrical
stimulus to a motor nerve to evoke a muscular response. Direct (M-wave) and/or
indirect (H-reflex) electrophysiological responses can be recorded at rest using
surface electromyography. Mechanical (twitch torque) responses can be quantified
with a force/torque ergometer. M-wave and twitch torque reflect neuromuscular
transmission and excitation-contraction coupling, whereas H-reflex provides an
index of spinal excitability. EMG activity and mechanical (superimposed twitch)
responses can also be recorded during maximal voluntary contractions to evaluate
voluntary activation level. Percutaneous nerve stimulation provides an assessment
of neuromuscular function in humans, and is highly beneficial especially for
studies evaluating neuromuscular plasticity following acute (fatigue) or chronic
(training/detraining) exercise.
PMID- 26436989
TI - Relationship between emotion and forgetting.
AB - A major determinant of forgetting in memory is the presence of interference in
the retrieval context. Previous research has shown that proactive interference
has less impact for emotional than neutral study material (Levens & Phelps,
2008). However, it is unclear how emotional content affects the impact of
interference in memory. Emotional content could directly affect the buildup of
interference, leading to reduced levels of interference. Alternatively, emotional
content could affect the controlled processes that resolve interference. The
present study employed the response deadline speed-accuracy trade-off procedure
to independently test these hypotheses. Participants studied 3-item lists
consisting of emotional or neutral images, immediately followed by a recognition
probe. Results indicated a slower rate of accrual for interfering material (lures
from previous study list) and lower levels of interference for emotional than
neutral stimuli, suggesting a direct impact of emotion on the buildup of
interference. In contrast to this beneficiary effect, resolution of interference
for emotional material was less effective than neutral material. These findings
can provide insight into the interactions of emotion and memory processes.
PMID- 26436990
TI - The quantitative genetics of disgust sensitivity.
AB - [Correction Notice: An Erratum for this article was reported in Vol 16(1) of
Emotion (see record 2015-57029-001). In the article, the name of author Joshua M.
Tybur was misspelled as Joshua M. Tyber. All versions of this article have been
corrected.] Response sensitivity to common disgust elicitors varies considerably
among individuals. The sources of these individual differences are largely
unknown. In the current study, we use a large sample of female identical and
nonidentical twins (N = 1,041 individuals) and their siblings (N = 170) to
estimate the proportion of variation due to genetic effects, the shared
environment, and other (residual) sources across multiple domains of disgust
sensitivity. We also investigate the genetic and environmental influences on the
covariation between the different disgust domains. Twin modeling revealed that
approximately half of the variation in pathogen, sexual, and moral disgust is due
to genetic effects. An independent pathways twin model also revealed that sexual
and pathogen disgust sensitivity were influenced by unique sources of genetic
variation, while also being significantly affected by a general genetic factor
underlying all 3 disgust domains. Moral disgust sensitivity, in contrast, did not
exhibit domain-specific genetic variation. These findings are discussed in light
of contemporary evolutionary approaches to disgust sensitivity.
PMID- 26436991
TI - Innovations 'Out of Place': Controversies Over IVF Beginnings in India Between
1978 and 2005.
AB - In 1978, the year the first in vitro fertilization (IVF) baby was born in the
United Kingdom, a research team in Kolkata reported that it too had successfully
produced an IVF baby in India. However, the claim was dismissed at the time,
because the experiment was conducted outside authorized institutions and
recognized centers of innovation--in short, because it was an innovation 'out of
place.' Tracing controversies over the case between 1978 and 2005, I show the
importance of space or place in processes of knowledge production and
recognition. Further, I explain the initial repudiation and subsequent partial
recognition of the claim through shifts in the landscape of legitimate spaces of
innovation. By discussing this specific case of the production of science and
technology in the Global South, I challenge conventional narratives of diffusion
that are prevalent in studies on the worldwide proliferation of reproductive
technologies.
PMID- 26436992
TI - Misconceptions about traumatic brain injury among U.S. Army behavioral health
professionals.
AB - PURPOSE/OBJECTIVE: To investigate the knowledge and misconceptions about
traumatic brain injury (TBI) held by behavioral health care professionals
providing services to an active-duty military population. RESEARCH METHOD/DESIGN:
Active duty U.S. Army psychologists, psychiatrists, social workers, and
psychiatric nurses from locations across the Department of Defense, and
behavioral health professionals from a major military hospital (N = 181) were
surveyed on 19 common myths and misconceptions about TBI (Gouvier, Prestholdt, &
Warner, 1988). Eight new items were added to the survey to more specifically
assess misconceptions pertaining to mild TBI (mTBI). RESULTS: Mean percentages
for the subcomponents of the questionnaire suggested that responses were
generally accurate for general information about brain damage (83.61% correct)
but less accurate for unconsciousness (45.81%), amnesia or memory loss (53%), and
recovery items (64.8%). The total percent correct was 51% on the new mTBI items
with a sizable minority of the sample viewing mTBI as being associated with
lengthier recovery and poorer outcome than what has been indicated by recent
research. CONCLUSION/IMPLICATIONS: Overall, misconceptions, particularly about
mTBI, are prevalent among U.S. Army behavioral health providers. These findings
raise concern about the dissemination of TBI information to health care
professionals in the U.S. Army and to military personnel who may not be receiving
accurate information about TBI recovery.
PMID- 26436993
TI - Functional recovery from neuroinvasive West Nile Virus: A tale of two courses.
AB - OBJECTIVE: In 2012, the highest numbers of West Nile Virus (WNV) cases were
reported by the Center for Disease Control since 2003. This outbreak included
over half of the identified patients being classified with one of the more
debilitating neuroinvasive subtypes of WNV. Despite improvements in diagnosis and
treatment options in symptom management, longitudinal research on WNV
neurocognitive and functional outcomes is limited by sample size, retrospective
review, and/or reliance on self-report measures for cognitive status and level of
independence. This study describes the cases of 2 patients diagnosed with WNV as
they complete rehabilitation across the continuum of care. RESEARCH METHOD:
Review of two cases that experience different rehabilitation outcomes 4-18 months
post diagnosis. RESULTS: The cases presented here demonstrate the potentially
differential courses of recovery and outcomes for physical (e.g., balance,
ambulation, upper extremity function), cognitive (e.g., attention, executive
functions, memory, language, visuospatial), and emotional functioning, as
assessed via measures administered by the patient's physical therapists and
neuropsychologists. These patients were evaluated as part of the standard
clinical practice to monitor changes, track recovery, and provide recommendations
across the continuum of care from admission to discharge from acute inpatient
rehabilitation, during outpatient day neurorehabilitation, and while receiving
outpatient neuropsychology services. CONCLUSIONS: These cases highlight the
variability in rehabilitative course for individuals diagnosed with WNV.
Consistent follow-up with patients is recommended to ensure management of
remitting and chronic symptoms.
PMID- 26436994
TI - Unprecedented Phthalocyanines Bearing Eight Di-butylamino Peripheral
Substituents: Synthesis, Spectroscopy, and Structure.
AB - Unprecedented 2,3,9,10,16,17,23,24-octakis(di-butylamino)phthalocyanine compounds
M{Pc[N(C4H9)2]8} (M = 2H, Mg, Cu, Zn) (1-4) were prepared and structurally
characterized on the basis of single-crystal X-ray diffraction analysis,
representing the first structurally characterized alkylamino-substituted
phthalocyanine examples. These novel phthalocyanine derivatives have also been
characterized by a wide range of spectroscopic methods including MALDI-TOF mass
spectra, NMR, electronic absorption, and IR spectroscopy in addition to elemental
analysis. Their electrochemistry was also studied by cyclic voltammetry.
PMID- 26436995
TI - Evaluation of Cytotoxicity and Cell Death Induced In Vitro by Saxitoxin in
Mammalian Cells.
AB - Since the cyanotoxin saxitoxin (STX) is a neurotoxin and induces ecological
changes in aquatic environments, a potential risk to public and environmental
health exists. However, data on STX-mediated cytotoxic and genotoxic effects are
still scare. In order to gain a better understanding of the effects of this
toxin, the cytotoxic and genotoxic potential of STX was examined in two mammalian
cell lines. Neuro 2A (N2A), a neuroblastoma mouse cell line, and Vero cell line,
derived from Vero green monkey kidney cells, were exposed to several
concentrations of STX ranging from 0.5 to 64 nM to determine cell viability,
induction of apoptosis (DNA fragmentation assay), and formation of micronuclei
(MN) (cytokinesis-block micronucleus assay; CBMN) following 24 h of incubation.
The half maximal effective concentration (EC50) values for STX calculated in cell
viability tests were 1.01 nM for N2A and 0.82 nM for Vero cells. With increasing
STX concentration there was evidence of DNA fragmentation indicating apoptosis
induction in Vero cells with a 50% increase in DNA fragmentation compared to
control at the highest STX concentration tested (3 nM). The results demonstrated
no significant changes in the frequency of micronucleated binucleated cells in
N2A and Vero cells exposed to STX, indicating the absence of genotoxicity under
these test conditions. There was no apparent cellular necrosis as evidenced by a
lack of formation of multinucleated cells. In conclusion, data reported herein
demonstrate that STX produced death of both cell types tested through an
apoptotic process.
PMID- 26436996
TI - A Decad(e) of Reasons to Contribute to a PLOS Community-Run Journal.
PMID- 26436998
TI - Tuning the Upconversion Luminescence Lifetimes of KYb2 F7 :Ho(3+) Nanocrystals
for Optical Multiplexing.
AB - Conventional luminescent color coding is limited by spectral overlap and the
interference of background fluorescence, thus restricting the number of
distinguishable identities that can be used in practice. Here, we demonstrate the
possibility of generating diverse time-domain codes, specially designed for a
single emission band, using lanthanide-doped upconversion nanocrystals. Based on
the knowledge of concentration quenching, the upconversion luminescence kinetics
of KYb2 F7 : Ho(3+) nanocrystals can be precisely controlled by modifying the
dopant concentration of Ho(3+) ions, resulting in a tunable emission lifetime
from 75.8 to 1944.5 MUs, which suggests the practicality of these time-domain
codes for optical multiplexing.
PMID- 26436999
TI - A Case Study of Fixed-Effects and Random-Effects Meta-Analysis Models for Genome
Wide Association Studies in Celiac Disease.
AB - BACKGROUND/AIMS: Amongst the many approaches to genome-wide association study
(GWAS) meta-analysis (MA), the most popular methods are based on fixed-effects
(FE) modeling because it tends to be the statistically most powerful approach in
the absence of heterogeneity. However, FE-based MA ignores the potential
heterogeneity that may exist between studies. The purpose of our analysis was to
test whether results from random effects (RE)-based methods that account for
heterogeneity differed significantly from the results that were originally
published. METHODS: We reanalyzed two GWAS FE-based MAs of celiac disease with RE
based methods: (1) a two-stage GWAS MA that includes 9,451 celiac disease cases
and 16,434 controls from 12 collections and (2) a single-stage GWAS MA using a
custom dense genotyping platform to capture low-frequency and rare variants in
12,041 cases and 12,228 controls from 7 collections. RESULTS: We present evidence
that SNPs at loci that were previously reported to be genome-wide significant
(GWS; p < 5 * 10(-8)) in either the two-stage GWAS MA or the single-stage GWAS MA
were not GWS when heterogeneity was accounted for by an RE MA method. CONCLUSION:
This case study highlights the strengths of RE MA methods in the presence of
heterogeneity and of pooled FE methods.
PMID- 26436997
TI - 'Emergency exit' of bone-marrow-resident CD34(+)DNAM-1(bright)CXCR4(+)-committed
lymphoid precursors during chronic infection and inflammation.
AB - During chronic inflammatory disorders, a persistent natural killer (NK) cell
derangement is observed. While increased cell turnover is expected, little is
known about whether and how NK-cell homeostatic balance is maintained. Here, flow
cytometric analysis of peripheral blood mononuclear cells in chronic inflammatory
disorders, both infectious and non-infectious, reveals the presence of a
CD34(+)CD226(DNAM-1)(bright)CXCR4(+) cell population displaying transcriptional
signatures typical of common lymphocyte precursors and giving rise to NK-cell
progenies with high expression of activating receptors and mature function and
even to alpha/beta T lymphocytes. CD34(+)CD226(bright)CXCR4(+) cells reside in
bone marrow, hardly circulate in healthy donors and are absent in cord blood.
Their proportion correlates with the degree of inflammation, reflecting lymphoid
cell turnover/reconstitution during chronic inflammation. These findings provide
insight on intermediate stages of NK-cell development, a view of emergency
recruitment of cell precursors, and upgrade our understanding and monitoring of
chronic inflammatory conditions.
PMID- 26437000
TI - Geographically Modified PageRank Algorithms: Identifying the Spatial
Concentration of Human Movement in a Geospatial Network.
AB - A network approach, which simplifies geographic settings as a form of nodes and
links, emphasizes the connectivity and relationships of spatial features.
Topological networks of spatial features are used to explore geographical
connectivity and structures. The PageRank algorithm, a network metric, is often
used to help identify important locations where people or automobiles concentrate
in the geographical literature. However, geographic considerations, including
proximity and location attractiveness, are ignored in most network metrics. The
objective of the present study is to propose two geographically modified PageRank
algorithms-Distance-Decay PageRank (DDPR) and Geographical PageRank (GPR)-that
incorporate geographic considerations into PageRank algorithms to identify the
spatial concentration of human movement in a geospatial network. Our findings
indicate that in both intercity and within-city settings the proposed algorithms
more effectively capture the spatial locations where people reside than
traditional commonly-used network metrics. In comparing location attractiveness
and distance decay, we conclude that the concentration of human movement is
largely determined by the distance decay. This implies that geographic proximity
remains a key factor in human mobility.
PMID- 26437001
TI - A novel glycobiomarker, Wisteria floribunda agglutinin macrophage colony
stimulating factor receptor, for predicting carcinogenesis of liver cirrhosis.
AB - Recently, we identified a novel liver fibrosis glycobiomarker, Wisteria
floribunda agglutinin (WFA)-reactive colony stimulating factor 1 receptor (WFA(+)
-CSF1R), using a glycoproteomics-based strategy. The aim of this study was to
assess the value of measuring WFA(+) -CSF1R levels for the prognosis of
carcinogenesis and outcome in liver cirrhosis (LC) patients with hepatitis C
virus (HCV). WFA(+) -CSF1R and Total-CSF1R levels were measured in serum samples
from 214 consecutive HCV-infected patients to evaluate their impact on
carcinogenesis and the survival of LC patients. Serum WFA(+) -CSF1R levels were
significantly higher in LC patients than chronic hepatitis (CH) patients (p <
0.001). The AUC of WFA(+) -CSF1R for predicting overall survival, calculated by
time-dependent ROC analysis, was 0.691 and the HR (per 1-SD increase) was 1.80
(95% CI, 1.23-2.62, p < 0.001). Furthermore, the survival rate of LC patients
with high WFA(+) -CSF1R levels (>= 310 ng/ml) was significantly worse than those
with lower levels (p < 0.01). The AUC of WFA(+) /total-CSF1R percentage (WFA(+)
CSF1R%) for predicting the cumulative carcinogenesis rate was 0.760, with an HR
of 1.66 (95% CI 1.26-2.20, p < 0.001). In fact, the carcinogenesis rate was
significantly higher in LC patients with a high WFA(+) -CSF1R% (>= 35%, p =
0.006). Assessing serum levels of WFA(+) -CSF1R has diagnostic value for
predicting carcinogenesis and the survival of LC patients.
PMID- 26437002
TI - Hybrid Modulation-Doping of Solution-Processed Ultrathin Layers of ZnO Using
Molecular Dopants.
AB - An alternative doping approach that exploits the use of organic donor/acceptor
molecules for the effective tuning of the free electron concentration in quasi-2D
ZnO transistor channel layers is reported. The method relies on the deposition of
molecular dopants/formulations directly onto the ultrathin ZnO channels. Through
careful choice of materials combinations, electron transfer from the dopant
molecule to ZnO and vice versa is demonstrated.
PMID- 26437003
TI - Characterizing effects of mild traumatic brain injury and posttraumatic stress
disorder on balance impairments in blast-exposed servicemembers and Veterans
using computerized posturography.
AB - The high rate of blast exposures experienced by U.S. servicemembers (SMs) during
the recent conflicts in Iraq and Afghanistan has resulted in frequent combat
related mild traumatic brain injuries (mTBIs). Dizziness and postural instability
can persist after mTBI as a component of postconcussion syndrome, but also occur
among the somatic complaints of posttraumatic stress disorder (PTSD). The goals
of this study were to examine the use of computerized posturography (CPT) to
objectively characterize chronic balance deficits after mTBI and to explore the
utility of CPT in distinguishing between combat and blast-exposed participants
with and without mTBI and PTSD. Data were analyzed from a subject pool of 166
combat-exposed SMs and Veterans who had a blast experience within the past 2 yr
while deployed. Using nonparametric tests and measures of impairment, we found
that balance was deficient in participants diagnosed with mTBI with posttraumatic
amnesia (PTA) or PTSD versus those with neither and that deficits were amplified
for participants with both diagnoses. In addition, unique deficiencies were found
using CPT for individuals having isolated mTBI with PTA and isolated PTSD.
Computerized balance assessment offers an objective technique to examine the
physiologic effects and provide differentiation between participants with combat
associated mTBI and PTSD.
PMID- 26437004
TI - Color Pattern on the Forewing of Micropterix (Lepidoptera: Micropterigidae):
Insights into the Evolution of Wing Pattern and Wing Venation in Moths.
AB - Wing patterns are key taxonomic characters that have long been used in
descriptions of Lepidoptera; however, wing pattern homologies are not understood
among different moth lineages. Here, we examine the relationship between wing
venation and wing pattern in the genus Micropterix, among the most basal extant
Lepidoptera, in order to evaluate the two existing predictive models that have
the potential to establish wing pattern element homologies for the order. The
location of wing pattern elements along the costal margin of the wing in
Micropterix is consistent with the predictions of the model proposed for
Tortricidae by Brown and Powell in 1991, later modified by Baixeras in 2002. The
predictive power of this model for such distantly related taxa suggests that the
model may hold across various superfamilies within Lepidoptera, and supports the
long-held notion that fasciae, not spots, are the most likely primitive wing
pattern elements for the order. In addition, the location of wing pattern
elements suggests that the wing vein commonly termed Sc1 may in fact be a
different vein, which Comstock identified in Trichoptera and referred to as "a."
PMID- 26437007
TI - Quantum Dynamics of the (18)O + (36)O2 Collision Process.
AB - We report full quantum cross sections and rate constants for the (18)O + (36)O2
> (36)O2 + (18)O collision process. This constitutes to the best of our knowledge
the first dynamical study of the (18)O(18)O(18)O system, with three identical
(18)O oxygen atoms. We emphasize the comparison with the (16)O + (32)O2 collision
as this latter presents the exact same features as the one treated here, except
the consistent change of mass for all three atoms. We find very similar behaviors
in the cross sections, and we confirm that the rates are faster when three
identical nuclei are involved. In particular, we cannot dynamically study this
system with classical trajectory methods, and we have to include properly the
indistinguishability of the three (18)O nuclei; however, we note some slight
differences with the (16)O(16)O(16)O benchmark system, and we focus our analysis
on their origin.
PMID- 26437006
TI - High-throughput Screening of Recalcitrance Variations in Lignocellulosic Biomass:
Total Lignin, Lignin Monomers, and Enzymatic Sugar Release.
AB - The conversion of lignocellulosic biomass to fuels, chemicals, and other
commodities has been explored as one possible pathway toward reductions in the
use of non-renewable energy sources. In order to identify which plants, out of a
diverse pool, have the desired chemical traits for downstream applications,
attributes, such as cellulose and lignin content, or monomeric sugar release
following an enzymatic saccharification, must be compared. The experimental and
data analysis protocols of the standard methods of analysis can be time
consuming, thereby limiting the number of samples that can be measured. High
throughput (HTP) methods alleviate the shortcomings of the standard methods, and
permit the rapid screening of available samples to isolate those possessing the
desired traits. This study illustrates the HTP sugar release and pyrolysis
molecular beam mass spectrometry pipelines employed at the National Renewable
Energy Lab. These pipelines have enabled the efficient assessment of thousands of
plants while decreasing experimental time and costs through reductions in labor
and consumables.
PMID- 26437005
TI - Effective intra-S checkpoint responses to UVC in primary human melanocytes and
melanoma cell lines.
AB - The objective of this study was to assess potential functional attenuation or
inactivation of the intra-S checkpoint during melanoma development. Proliferating
cultures of skin melanocytes, fibroblasts, and melanoma cell lines were exposed
to increasing fluences of UVC and intra-S checkpoint responses were quantified.
Melanocytes displayed stereotypic intra-S checkpoint responses to UVC
qualitatively and quantitatively equivalent to those previously demonstrated in
skin fibroblasts. In comparison with fibroblasts, primary melanocytes displayed
reduced UVC-induced inhibition of DNA strand growth and enhanced degradation of
p21Waf1 after UVC, suggestive of enhanced bypass of UVC-induced DNA
photoproducts. All nine melanoma cell lines examined, including those with
activating mutations in BRAF or NRAS oncogenes, also displayed proficiency in
activation of the intra-S checkpoint in response to UVC irradiation. The results
indicate that bypass of oncogene-induced senescence during melanoma development
was not associated with inactivation of the intra-S checkpoint response to UVC
induced DNA replication stress.
PMID- 26437010
TI - A 6-Year-Old Boy With Fever, Emesis, Rash, and an Acute Abdomen.
PMID- 26437011
TI - Glyburide vs Insulin and Adverse Pregnancy Outcomes.
PMID- 26437012
TI - Glyburide vs Insulin and Adverse Pregnancy Outcomes.
PMID- 26437013
TI - Glyburide vs Insulin and Adverse Pregnancy Outcomes--Reply.
PMID- 26437014
TI - Kidney Stones in Children and Adolescents.
PMID- 26437015
TI - Associations Between Antibullying Policies and Bullying in 25 States.
AB - IMPORTANCE: Bullying is the most widespread form of peer aggression in schools.
In an effort to address school bullying, 49 states have passed antibullying
statutes. Despite the ubiquity of these policies, there has been limited
empirical examination of their effectiveness in reducing students' risk of being
bullied. OBJECTIVE: To evaluate the effectiveness of antibullying legislation in
reducing students' risk of being bullied and cyberbullied, using data from 25
states in the United States. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional
observational study was conducted using a population-based survey of 63 635
adolescents in grades 9 to 12 from 25 states participating in the 2011 Youth Risk
Behavior Surveillance System study (September 2010-December 2011). Data on
antibullying legislation were obtained from the US Department of Education (DOE),
which commissioned a systematic review of state laws in 2011. The report
identified 16 key components that were divided into the following 4 broad
categories: purpose and definition of the law, district policy development and
review, school district policy components (eg, responsibilities for reporting
bullying incidents), and additional components (eg, how policies are
communicated). Policy variables from 25 states were linked to individual-level
data from the Youth Risk Behavior Surveillance System on experiencing bullying
and cyberbullying. Analyses were conducted between March 1, 2014, and December 1,
2014. EXPOSURE: State antibullying legislation. MAIN OUTCOMES AND MEASURES:
Exposure to bullying and cyberbullying in the past 12 months. RESULTS: There was
substantial variation in the rates of bullying and cyberbullying across states.
After controlling for relevant state-level confounders, students in states with
at least 1 DOE legislative component in the antibullying law had a 24% (95% CI,
15%-32%) reduced odds of reporting bullying and 20% (95% CI, 9%-29%) reduced odds
of reporting cyberbullying compared with students in states whose laws had no DOE
legislative components. Three individual components of antibullying legislation
were consistently associated with decreased odds of exposure to both bullying and
cyberbullying: statement of scope, description of prohibited behaviors, and
requirements for school districts to develop and implement local policies.
CONCLUSIONS AND RELEVANCE: Antibullying policies may represent effective
intervention strategies for reducing students' risk of being bullied and
cyberbullied in schools.
PMID- 26437016
TI - Total Direct Medical Expenses and Characteristics of Privately Insured
Adolescents Who Incur High Costs.
AB - IMPORTANCE: Accountable care payment models aim to reduce total direct medical
expenses for high-cost patients through improved quality of care and preventive
health services. Little is known about health care expenditures of privately
insured adolescents, especially those who incur high costs. OBJECTIVES: To assess
health care expenditures for high-cost adolescents and to describe the patient
characteristics associated with high medical costs. DESIGN, SETTING, AND
PARTICIPANTS: A retrospective cohort analysis was conducted of data from January
1 to December 31, 2012, of 13,103 privately insured adolescents aged 13 to 21
years (mean [SD] age, 16.3 [2.4] years; 6764 [51.6%] males) at 82 independent
pediatric primary care practices in Massachusetts. Analysis was conducted from
April 1, 2014, to April 1, 2015. MAIN OUTCOMES AND MEASURES: We compared
demographic (age, sex, median income by zip code) and clinical (obesity,
behavioral health problem, complex chronic condition) characteristics between
high-cost (top 1%) and non-high-cost adolescents. We assigned high-cost
adolescents to clinical categories using software from the Agency for Healthcare
Research and Quality to describe clinically relevant patterns of spending.
RESULTS: Total direct medical expenses were $41.2 million for the entire cohort
and a median $1167 per patient. A total of 132 (1.0%) patients with the highest
costs accounted for 23.6% of expenses of the cohort, with a median $52,577 per
patient. Mental health disorders were the most common diagnosis in high-cost
patients; 78 (59.1%) of these patients had at least 1 behavioral health
diagnosis. Pharmacy costs accounted for 28.4% of total direct medical expenses of
high-cost patients; primary care accounted for 1.0%. Characteristics associated
with being a high-cost patient included having 1 complex chronic condition
(relative risk [RR], 6.5; 95% CI, 4.7-9.0), having 2 or more complex chronic
conditions (RR, 23.5; 95% CI, 14.2-39.1), having any behavioral health diagnosis
(RR, 3.6; 95% CI, 2.6-5.1), and obesity (RR, 2.0; 95% CI, 1.3-3.0). CONCLUSIONS
AND RELEVANCE: Total direct medical expenses for privately insured high-cost
adolescents are associated with medical complexity, mental health conditions, and
obesity. Cost reduction strategies in similar populations should be tailored to
these cost drivers.
PMID- 26437017
TI - Difficult laparoscopic total mesorectal excision after preoperative colonoscopic
tattooing.
PMID- 26437018
TI - Burden of vaccine preventable diseases at large events.
AB - BACKGROUND: Large events or mass gatherings (MGs) are known to amplify the risk
of infectious diseases, many of which can be prevented by vaccination. In this
review we have evaluated the burden of vaccine preventable diseases (VPDs) in
MGs. METHODS: Major databases like PubMed and Embase, Google Scholar and
pertinent websites were searched by using MeSH terms and text words; this was
supplemented by hand searching. Following data abstraction, the pooled estimate
of the burden of VPDs was calculated when possible; otherwise a narrative
synthesis was conducted. RESULTS: In the past, at religious MGs like Hajj and
Kumbh Mela, cholera caused explosive outbreaks; but currently respiratory
infections, notably influenza, are the commonest diseases not only at Hajj but
also at World Youth Day and Winter Olympiad. The recent cumulative attack rate of
influenza at Hajj is 8.7% (range 0.7-15.8%), and the cumulative prevalence is
3.6% (range: 0.3-38%). Small outbreaks of measles (13-42 cases per event) have
been reported at sport, entertainment and religious events. A sizeable outbreak
(>200 cases) was reported following a special Easter Festival in Austria. An
outbreak of hepatitis A occurred following the 'Jam bands' music festival. Other
VPDs including pneumococcal disease, pertussis and tuberculosis have been
reported in relation to MG attendance. CONCLUSION: VPDs not only affect the
participants of MGs but also their contacts; vaccine uptake is variable and
vaccine implementation is likely to have beneficial effects. Research to address
the knowledge gaps surrounding VPDs at MGs is needed.
PMID- 26437019
TI - Reversible High-Grade Atrioventricular Block Associated With Cocaine Use.
PMID- 26437020
TI - Quantitative Phosphoproteomics Revealed Glucose-Stimulated Responses of Islet
Associated with Insulin Secretion.
AB - As central tissue of glucose homeostasis, islet has been an important focus of
diabetes research. Phosphorylation plays pivotal roles in islet function,
especially in islet glucose-stimulated insulin secretion. A systematic view on
how phosphorylation networks were coordinately regulated in this process remains
lacking, partially due to the limited amount of islets from an individual for a
phosphoproteomic analysis. Here we optimized the in-tip and best-ratio
phosphopeptide enrichment strategy and a SILAC-based workflow for processing rat
islet samples. With limited islet lysates from each individual rat (20-47 MUg),
we identified 8539 phosphosites on 2487 proteins. Subsequent quantitative
analyses uncovered that short-term (30 min) high glucose stimulation induced
coordinate responses of islet phosphoproteome on multiple biological levels,
including insulin secretion related pathways, cytoskeleton dynamics, protein
processing in ER and Golgi, transcription and translation, and so on.
Furthermore, three glucose-responsive phosphosites (Prkar1a pT75pS77 and Tagln2
pS163) from the data set were proved to be correlated with insulin secretion.
Overall, we initially gave an in-depth map of islet phosphoproteome regulated by
glucose on individual rat level. This was a significant addition to our knowledge
about how phosphorylation networks responded in insulin secretion. Also, the list
of changed phosphosites was a valuable resource for molecular researchers in
diabetes field.
PMID- 26437022
TI - Catalytic Protein Film Electrochemistry Provides a Direct Measure of the
Tetrathionate/Thiosulfate Reduction Potential.
AB - The tetrathionate/thiosulfate interconversion is a two-electron process: S4O6(2-)
+ 2 e(-) <-> 2 S2O3(2-). Both transformations can support bacterial growth since
S2O3(2-) provides an energy source, while S4O6(2-) serves as respiratory electron
acceptor. Interest in the corresponding S2O3(2-) oxidation also arises from its
widespread use in volumetric analysis of oxidizing agents and bleach
neutralization during water treatment. Here we report protein film
electrochemistry that defines the reduction potential of the S4O6(2-)/S2O3(2-)
couple. The relevant interconversion is not reversible at inert electrodes.
However, facile reduction of S4O6(2-) to S2O3(2-) and the reverse reaction are
catalyzed by enzymes of the thiosulfate dehydrogenase, TsdA, family adsorbed on
graphite electrodes. Zero-current potentials measured with different enzymes, at
three pH values, and multiple S4O6(2-) and S2O3(2-) concentrations together with
the relevant Nernst equation resolved the tetrathionate/thiosulfate reduction
potential as +198 +/- 4 mV versus SHE. This potential lies in the ~250 mV window
encompassing previously reported values calculated from parameters including the
free energy of formation. However, the value is considerably more positive than
widely used in discussions of bacterial bioenergetics. As a consequence anaerobic
respiration by tetrathionate reduction is likely to be more prevalent than
presently thought in tetrathionate-containing environments such as marine
sediments and the human gut.
PMID- 26437021
TI - Bik Mediates Caspase-Dependent Cleavage of Viral Proteins to Promote Influenza A
Virus Infection.
AB - Influenza virus induces apoptosis in infected cells to promote viral replication
by manipulating the host cell death signaling pathway. Although some Bcl-2 family
proteins play a role in the replication of influenza A virus (IAV), the role of
cell death pathways in the viral replication cycle is unclear. We investigated
whether deficiency of the proapoptotic Bcl-2 family protein, Bik, plays a role in
IAV replication. IAV replication was attenuated in mouse airway epithelial cells
(MAECs) from bik(-/-) compared with bik(+/+) mice, as indicated by reduced viral
titers. Bik(-/-) MAECs showed more stable transepithelial resistance after
infection than did bik(+/+) MAECs, were less sensitive to infection-induced cell
death, and released fewer copies of viral RNA. Similar results were obtained when
Bik expression was suppressed in human airway epithelial cells (HAECs). Bik(+/+)
mice lost weight drastically and died within 8 days of infection, whereas 75% of
bik(-/-) mice survived infection for 14 days and were 10-fold less likely to die
from infection compared with bik(+/+) mice. IAV infection activated caspase 3 in
bik(+/+) but not in bik(-/-) MAECs. Cleavage of viral nucleoprotein and M2
proteins were inhibited in bik(-/-) MAECs and when caspase activation was
inhibited in HAECs. Furthermore, Bik deficiency impaired cytoplasmic export of
viral ribonucleoprotein. These studies suggest a link between Bik-mediated
caspase activation and cleavage of viral proteins. Thus, inhibition of
proapoptotic host factors such as Bik and downstream mediators of cell death may
represent a novel approach to influenza treatment.
PMID- 26437023
TI - Chemically Crushed Wood Cellulose Fiber towards High-Performance Sodium-Ion
Batteries.
AB - Carbon materials have attracted great interest as an anode for sodium-ion
batteries (SIBs) due to their high performance and low cost. Here, we studied
natural wood fiber derived hard carbon anodes for SIBs considering the abundance
and low cost of wood. We discovered that a thermal carbonization of wood fiber
led to a porous carbon with a high specific surface area of 586 m(2) g(-1), while
a pretreatment with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) could
effectively decrease it to 126 m(2) g(-1). When evaluating them as anodes for
SIBs, we observed that the low surface area carbon resulted in a high initial
Coulombic efficiency of 72% compared to 25% of the high surface area carbon. More
importantly, the low surface area carbon exhibits an excellent cycling stability
that a desodiation capacity of 196 mAh g(-1) can be delivered over 200 cycles at
a current density of 100 mA g(-1), indicating a promising anode for low-cost
SIBs.
PMID- 26437024
TI - Hospital of diagnosis and likelihood of surgical treatment for pancreatic cancer.
AB - BACKGROUND: Surgical resection for pancreatic cancer offers the only chance of
cure. Assessment of the resectability of a pancreatic tumour is therefore of
great importance. The aim of the study was to investigate whether centre of
diagnosis influences the likelihood of surgery and whether this affects long-term
survival. METHODS: Patients diagnosed with non-metastasized pancreatic cancer
(M0) between 2005 and 2013 in the Netherlands were selected from the Netherlands
Cancer Registry. Hospitals were classified as a pancreatic centre (at least 20
resections/year) or a non-pancreatic centre (fewer than 20 resections/year). The
relationship between centre of diagnosis and likelihood of surgery was analysed
by multivariable logistic regression. Influence of centre on overall survival was
assessed by means of multivariable Cox regression analysis. RESULTS: Some 8141
patients were diagnosed with non-metastasized pancreatic cancer, of whom 3123
(38.4 per cent) underwent surgery. Of the 2712 patients diagnosed in one of 19
pancreatic centres, 52.4 per cent had exploratory laparotomy compared with 31.4
per cent of 5429 patients diagnosed in one of 74 non-pancreatic centres (P <
0.001). A pancreatectomy was performed in 42.8 and 24.6 per cent of the patients
respectively (P < 0.001). Multivariable analysis revealed that patients diagnosed
in a pancreatic centre had a higher chance of undergoing surgery (odds ratio
2.21, 95 per cent c.i. 1.98 to 2.47). Centre of diagnosis was not associated with
improved long-term survival (hazard ratio 0.95, 95 per cent c.i. 0.91 to 1.00).
CONCLUSION: Patients with non-metastasized pancreatic cancer had a greater
likelihood of having surgical treatment when the diagnosis was established in a
pancreatic centre.
PMID- 26437025
TI - Reticulocyte hemoglobin content does not differentiate true from functional iron
deficiency in dogs.
AB - BACKGROUND: True and functional iron deficiency can result in anemia. Current
tests to assess iron status often do not allow differentiation between these
entities, which can affect optimal treatment. Previous work suggested low
reticulocyte hemoglobin content (CHr) may be an early indicator of iron
deficiency. OBJECTIVE: This study aimed to correlate several inflammation markers
with CHr values in dogs. We hypothesize that dogs with low CHr values have
hematologic and biochemical evidence of inflammation. METHODS: Animals with CHr
values below the reference interval were included in the low CHr group, while
dogs with normal or increased CHr were included in the control group. HCT, MCV,
CHr, reticulocyte mean cell volume (MCVr), concentrations of serum iron, C
reactive protein (CRP), ferritin, and ceruloplasmin, and total iron-binding
capacity (TIBC), percent transferrin saturation (% sat), and total WBC,
neutrophil, and monocyte counts were determined. Nonparametric tests were
performed; median values and percentage of abnormalities between each group were
compared. RESULTS: Relative to control dogs, animals in the low CHr group had
higher median values for CRP, ferritin, ceruloplasmin, and WBC concentration (P
<= .05), and lower median values for HCT and MCV (P <= .0001). Higher frequencies
of abnormalities for CRP, ferritin, WBC, neutrophil, and monocyte concentrations
(P <= .02) were present in the low CHr group. CONCLUSIONS: Dogs with low CHr
values often have evidence of inflammation, but low CHr did not reliably predict
Fe deficiency. Additional diagnostic tests are needed to differentiate true and
functional iron deficiency.
PMID- 26437026
TI - Ethanol and High-Value Terpene Co-Production from Lignocellulosic Biomass of
Cymbopogon flexuosus and Cymbopogon martinii.
AB - Cymbopogon flexuosus, lemongrass, and C. martinii, palmarosa, are perennial
grasses grown to produce essential oils for the fragrance industry. The
objectives of this study were (1) to evaluate biomass and oil yields as a
function of nitrogen and sulfur fertilization, and (2) to characterize their
utility for lignocellulosic ethanol compared to Panicum virgatum (switchgrass).
Mean biomass yields were 12.83 Mg lemongrass ha-1 and 15.11 Mg palmarosa ha-1
during the second harvest year resulting in theoretical biofuel yields of 2541
and 2569 L ethanol ha-1 respectively compared to reported 1749-3691 L ethanol ha
1 for switchgrass. Pretreated lemongrass yielded 198 mL ethanol (g biomass)-1 and
pretreated palmarosa yielded 170 mL ethanol (g biomass)-1. Additionally,
lemongrass yielded 85.7 kg essential oil ha-1 and palmarosa yielded 67.0 kg ha-1
with an estimated value of USD $857 and $1005 ha-1. These data suggest that dual
use crops such as lemongrass and palmarosa may increase the economic viability of
lignocellulosic biofuels.
PMID- 26437027
TI - Magnetic Sphincter Augmentation for Gastroesophageal Reflux at 5 Years: Final
Results of a Pilot Study Show Long-Term Acid Reduction and Symptom Improvement.
AB - BACKGROUND: As previously reported, the magnetic sphincter augmentation device
(MSAD) preserves gastric anatomy and results in less severe side effects than
traditional antireflux surgery. The final 5-year results of a pilot study are
reported here. PATIENTS AND METHODS: A prospective, multicenter study evaluated
safety and efficacy of the MSAD for 5 years. Prior to MSAD placement, patients
had abnormal esophageal acid and symptoms poorly controlled by proton pump
inhibitors (PPIs). Patients served as their own control, which allowed comparison
between baseline and postoperative measurements to determine individual treatment
effect. At 5 years, gastroesophageal reflux disease (GERD)-Health Related Quality
of Life (HRQL) questionnaire score, esophageal pH, PPI use, and complications
were evaluated. RESULTS: Between February 2007 and October 2008, 44 patients (26
males) had an MSAD implanted by laparoscopy, and 33 patients were followed up at
5 years. Mean total percentage of time with pH <4 was 11.9% at baseline and 4.6%
at 5 years (P < .001), with 85% of patients achieving pH normalization or at
least a 50% reduction. Mean total GERD-HRQL score improved significantly from
25.7 to 2.9 (P < .001) when comparing baseline and 5 years, and 93.9% of patients
had at least a 50% reduction in total score compared with baseline. Complete
discontinuation of PPIs was achieved by 87.8% of patients. No complications
occurred in the long term, including no device erosions or migrations at any
point. CONCLUSIONS: Based on long-term reduction in esophageal acid, symptom
improvement, and no late complications, this study shows the relative safety and
efficacy of magnetic sphincter augmentation for GERD.
PMID- 26437028
TI - MMP21 is mutated in human heterotaxy and is required for normal left-right
asymmetry in vertebrates.
AB - Heterotaxy results from a failure to establish normal left-right asymmetry early
in embryonic development. By whole-exome sequencing, whole-genome sequencing and
high-throughput cohort resequencing, we identified recessive mutations in MMP21
(encoding matrix metallopeptidase 21) in nine index cases with heterotaxy. In
addition, Mmp21-mutant mice and mmp21-morphant zebrafish displayed heterotaxy and
abnormal cardiac looping, respectively, suggesting a new role for extracellular
matrix remodeling in the establishment of laterality in vertebrates.
PMID- 26437029
TI - Discovery of four recessive developmental disorders using probabilistic genotype
and phenotype matching among 4,125 families.
AB - Discovery of most autosomal recessive disease-associated genes has involved
analysis of large, often consanguineous multiplex families or small cohorts of
unrelated individuals with a well-defined clinical condition. Discovery of new
dominant causes of rare, genetically heterogeneous developmental disorders has
been revolutionized by exome analysis of large cohorts of phenotypically diverse
parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and
genetically heterogeneous developmental disorders and identified four new
autosomal recessive disorders. These four disorders were identified by
integrating Mendelian filtering (selecting probands with rare, biallelic and
putatively damaging variants in the same gene) with statistical assessments of
(i) the likelihood of sampling the observed genotypes from the general population
and (ii) the phenotypic similarity of patients with recessive variants in the
same candidate gene. This new paradigm promises to catalyze the discovery of
novel recessive disorders, especially those with less consistent or nonspecific
clinical presentations and those caused predominantly by compound heterozygous
genotypes.
PMID- 26437030
TI - DNA methylome analysis in Burkitt and follicular lymphomas identifies
differentially methylated regions linked to somatic mutation and transcriptional
control.
AB - Although Burkitt lymphomas and follicular lymphomas both have features of
germinal center B cells, they are biologically and clinically quite distinct.
Here we performed whole-genome bisulfite, genome and transcriptome sequencing in
13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation
positive follicular lymphoma and four normal germinal center B cell samples.
Comparison of Burkitt and follicular lymphoma samples showed differential
methylation of intragenic regions that strongly correlated with expression of
associated genes, for example, genes active in germinal center dark-zone and
light-zone B cells. Integrative pathway analyses of regions differentially
methylated in Burkitt and follicular lymphomas implicated DNA methylation as
cooperating with somatic mutation of sphingosine phosphate signaling, as well as
the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas.
Taken together, our results demonstrate a tight connection between somatic
mutation, DNA methylation and transcriptional control in key B cell pathways
deregulated differentially in Burkitt lymphoma and other germinal center B cell
lymphomas.
PMID- 26437032
TI - Intron retention is a widespread mechanism of tumor-suppressor inactivation.
AB - A substantial fraction of disease-causing mutations are pathogenic through
aberrant splicing. Although genome profiling studies have identified somatic
single-nucleotide variants (SNVs) in cancer, the extent to which these variants
trigger abnormal splicing has not been systematically examined. Here we analyzed
RNA sequencing and exome data from 1,812 patients with cancer and identified ~900
somatic exonic SNVs that disrupt splicing. At least 163 SNVs, including 31
synonymous ones, were shown to cause intron retention or exon skipping in an
allele-specific manner, with ~70% of the SNVs occurring on the last base of
exons. Notably, SNVs causing intron retention were enriched in tumor suppressors,
and 97% of these SNVs generated a premature termination codon, leading to loss of
function through nonsense-mediated decay or truncated protein. We also
characterized the genomic features predictive of such splicing defects. Overall,
this work demonstrates that intron retention is a common mechanism of tumor
suppressor inactivation.
PMID- 26437031
TI - Integrated molecular analysis of adult T cell leukemia/lymphoma.
AB - Adult T cell leukemia/lymphoma (ATL) is a peripheral T cell neoplasm of largely
unknown genetic basis, associated with human T cell leukemia virus type-1 (HTLV
1) infection. Here we describe an integrated molecular study in which we
performed whole-genome, exome, transcriptome and targeted resequencing, as well
as array-based copy number and methylation analyses, in a total of 426 ATL cases.
The identified alterations overlap significantly with the HTLV-1 Tax interactome
and are highly enriched for T cell receptor-NF-kappaB signaling, T cell
trafficking and other T cell-related pathways as well as immunosurveillance.
Other notable features include a predominance of activating mutations (in PLCG1,
PRKCB, CARD11, VAV1, IRF4, FYN, CCR4 and CCR7) and gene fusions (CTLA4-CD28 and
ICOS-CD28). We also discovered frequent intragenic deletions involving IKZF2,
CARD11 and TP73 and mutations in GATA3, HNRNPA2B1, GPR183, CSNK2A1, CSNK2B and
CSNK1A1. Our findings not only provide unique insights into key molecules in T
cell signaling but will also guide the development of new diagnostics and
therapeutics in this intractable tumor.
PMID- 26437034
TI - Hedgehog- and mTOR-targeted therapies for advanced basal cell carcinomas.
AB - Basal cell carcinomas (BCCs) are the most frequent human cancer. Over 90% of all
BCCs have a mutation in PTCH1 or smoothened, two conducting proteins of the
Hedgehog pathway. They rarely progress deeply and metastasize; however, if they
do, these advanced basal cell carcinoma become amenable to treatment by
inhibiting the Hedgehog and the P13K-mTOR pathways. Such innovative drugs include
vismodegib, cyclopamine, itraconazole, everolimus and a few other agents that are
in early clinical development.
PMID- 26437035
TI - The effect of ALD-grown Al2O3 on the refractive index sensitivity of CVD gold
coated optical fiber sensors.
AB - The combined effect of nanoscale dielectric and metallic layers prepared by
atomic layer deposition (ALD) and chemical vapor deposition (CVD) on the
refractometric properties of tilted optical fiber Bragg gratings (TFBG) is
studied. A high index intermediate layer made up of either 50 nm or 100 nm layers
of Al2O3 (refractive index near 1.62) was deposited by ALD and followed by thin
gold layers (30-65 nm) deposited from a known single-source gold (I)
iminopyrrolidinate CVD precursor. The fabricated devices were immersed in
different surrounding refractive indices (SRI) and the spectral transmission
response of the TFBGs was measured. Preliminary results indicate that the
addition of the dielectric Al2O3 pre-coating enhances the SRI sensitivity by up
to 75% but this enhancement is highly dependent on the polarization and
dielectric thickness. In fact, the sensitivity decreases by up to 50% for certain
cases. These effects are discussed with support from TFBG simulations and models,
by quantifying the penetration of the evanescently coupled light out of the fiber
through the various coating layers. Additional characterization studies have been
carried out on these samples to further correlate the optical behaviour of the
coated TFBGs with the physical properties of the gold and Al2O3 layers, using
atomic force microscopy x-ray photoelectron spectroscopy and an ensemble of other
optical and x-ray absorption spectroscopy techniques. The purity, roughness, and
morphology of gold thin films deposited by CVD onto the dielectric-TFBG surface
are also provided.
PMID- 26437033
TI - Genomic landscapes of breast fibroepithelial tumors.
AB - Breast fibroepithelial tumors comprise a heterogeneous spectrum of pathological
entities, from benign fibroadenomas to malignant phyllodes tumors. Although MED12
mutations have been frequently found in fibroadenomas and phyllodes tumors, the
landscapes of genetic alterations across the fibroepithelial tumor spectrum
remain unclear. Here, by performing exome sequencing of 22 phyllodes tumors
followed by targeted sequencing of 100 breast fibroepithelial tumors, we observed
three distinct somatic mutation patterns. First, we frequently observed MED12 and
RARA mutations in both fibroadenomas and phyllodes tumors, emphasizing the
importance of these mutations in fibroepithelial tumorigenesis. Second, phyllodes
tumors exhibited mutations in FLNA, SETD2 and KMT2D, suggesting a role in driving
phyllodes tumor development. Third, borderline and malignant phyllodes tumors
harbored additional mutations in cancer-associated genes. RARA mutations
exhibited clustering in the portion of the gene encoding the ligand-binding
domain, functionally suppressed RARA-mediated transcriptional activation and
enhanced RARA interactions with transcriptional co-repressors. This study
provides insights into the molecular pathogenesis of breast fibroepithelial
tumors, with potential clinical implications.
PMID- 26437036
TI - Generalized Anxiety Disorder and Pain.
AB - In this article, the co-occurrence of anxiety disorders (in particular
generalized anxiety disorder) and pain conditions is described, characteristics
of chronic pain are explained, and data on the prevalence of co-comorbidity of
both conditions are reviewed. Further, hypotheses on the possible psychosocial
and neurobiological backgrounds of the high rate of co-occurrence are discussed.
This review will also focus on the role of 'unexplained' pain syndromes (e.g.
somatic symptom disorder and fibromyalgia) and anxiety. Finally, we address
possible treatment strategies for patients with both conditions. There is a need
for a rigorous assessment of pain syndromes in generalized anxiety disorder and
anxiety in chronic pain conditions in order to prevent subsequent mortality by
early treatment of both conditions.
PMID- 26437038
TI - The same but completely different.
PMID- 26437037
TI - Xenopus laevis as a Model to Identify Translation Impairment.
AB - Protein synthesis is a fundamental process to gene expression impacting diverse
biological processes notably adaptation to environmental conditions. The
initiation step, which involves the assembly of the ribosomal subunits at the
mRNA initiation codon, involved initiation factor including eIF4G1. Defects in
this rate limiting step of translation are linked to diverse disorders. To study
the potential consequences of such deregulations, Xenopus laevis oocytes
constitute an attractive model with high degrees of conservation of essential
cellular and molecular mechanisms with human. In addition, during meiotic
maturation, oocytes are transcriptionally repressed and all necessary proteins
are translated from preexisting, maternally derived mRNAs. This inexpensive model
enables exogenous mRNA to become perfectly integrated with an effective
translation. Here is described a protocol for assessing translation with a factor
of interest (here eIF4G1) using stored maternal mRNA that are the first to be
polyadenylated and translated during oocyte maturation as a physiological
readout. At first, mRNA synthetized by in vitro transcription of plasmids of
interest (here eIF4G1) are injected in oocytes and kinetics of oocyte maturation
by Germinal Vesicle Breakdown detection is determined. The studied maternal mRNA
target is the serine/threonine-protein-kinase mos. Its polyadenylation and its
subsequent translation are investigated together with the expression and
phosphorylation of proteins of the mos signaling cascade involved in oocyte
maturation. Variations of the current protocol to put forward translational
defects are also proposed to emphasize its general applicability. In light of
emerging evidence that aberrant protein synthesis may be involved in the
pathogenesis of neurological disorders, such a model provides the opportunity to
easily assess this impairment and identify new targets.
PMID- 26437039
TI - Erratum: Viewpoint article in our March 2015 issue--author details.
AB - The Viewpoint article entitled 'Peer support workers: an untapped resource in
primary mental health care' was published with incorrect author details as
supplied. The first author of the paper is Juan J Tellez. The paper should be
correctly cited as: Tellez JJ, Kidd J. Peer support workers: an untapped resource
in primary mental health care. J Prim Health Care. 2015;7(1):84-87.
PMID- 26437040
TI - General practitioners gatekeepers for referral but neurosurgeons gatekeepers for
investigations.
PMID- 26437041
TI - The distribution and frequency of blood lipid testing by sociodemographic status
among adults in Auckland, New Zealand.
AB - INTRODUCTION: National cardiovascular disease (CVD) guidelines recommend that
adults have cholesterol levels monitored regularly. However, little is known
about the extent and equity of cholesterol testing in New Zealand. AIM: To
investigate the distribution and frequency of blood lipid testing by
sociodemographic status in Auckland, New Zealand. METHODS: We anonymously linked
five national health datasets (primary care enrolment, laboratory tests,
pharmaceuticals, hospitalisations and mortality) to identify adults aged >=25
years without CVD or diabetes who had their lipids tested in 2006-2010, by age,
gender, ethnicity and area of residence and deprivation. Multivariate logistic
regression was used to estimate the likelihood of testing associated with these
factors. RESULTS: Of the 627 907 eligible adults, 66.3% had at least one test
between 2006 and 2010. Annual testing increased from 24.7% in 2006 to 35.1% in
2010. Testing increased with age similarly for men and women. Indian people were
87% more likely than New Zealand European and Others (NZEO) to be tested, Pacific
people 8% more likely, but rates for Maori were similar to NZEO. There was marked
variation within the region, with residents of the most deprived areas less
likely to be tested than residents in least deprived areas. DISCUSSION:
Understanding differences within and between population groups supports the
development of targeted strategies for better service utilisation. While lipid
testing has increased, sociodemographic variations persist by place of residence,
and deprivation. Of the high CVD risk populations, lipid testing for Maori and
Pacific is not being conducted according to need.
PMID- 26437042
TI - The Green Prescription Active Families programme in Taranaki, New Zealand 2007
2009: Did it reach children in need?
AB - INTRODUCTION: The Green Prescription Active Families (GRxAF) programme focuses on
overweight/obese children and adolescents, and is family/whanau based. It is an
intervention supporting lifestyle changes through weekly sessions (nutrition
advice and/or physical activity), and goal setting for the family/whanau for up
to 12 months. AIMS: To describe the GRxAF programme in Taranaki and evaluate its
reach and engagement, especially for those most at risk of obesity. METHODS:
Participant files for each referred child from May 2007 to December 2009 were
reviewed. Baseline demographic data, programme graduation information, and weekly
activity session attendance were collected. RESULTS: Of the 109 participants
during the audit period, 39% were Maori , 57% New Zealand European (NZE), 3%
Pacific, and 1% Other ethnicity. Mean age at entry was 10 (range 4-17) years.
Mean duration of programme involvement was five (range 0-12) months. Overall,
33/60 (55%) of the participants completing the programme during the audit period
graduated, having made steps towards healthy lifestyle change. In comparison with
NZE (68%), a smaller proportion of Maori (40%) graduated (p=0.04). In comparison
with those who attended no sessions, participants who attended any sessions were
more likely to make positive changes (OR=3.65, 95% CI 1.24-10.8). DISCUSSION:
GRxAF in Taranaki met a need for some obese/overweight children, but not for all
families/whanau, especially those over-represented in childhood obesity
statistics. Programme delivery for Maori requires improvement, and assessment of
readiness to make lifestyle change as an enrolment criteria for all participants
is recommended.
PMID- 26437043
TI - Optimising neurosurgical outpatient care: a paradigm shift?
AB - INTRODUCTION: The Wellington Regional Hospital (WRH) neurosurgical service has
noted a substantial increase in patient volumes over the last decade, with
referrals to the neurosurgical outpatient clinic appearing to have increased even
more substantially. AIM: To quantify the increase in referrals to the WRH
neurosurgical outpatient service and to determine whether this has translated
into an increase in the number of neurosurgical procedures performed. METHODS:
All referrals to the WRH neurosurgical department from the lower North and upper
South Islands of New Zealand spanning 10 years were collected. Key outcome data
were the number of interventions performed. In addition to GP referrals, all
specialist referrals to the WRH neurosurgical outpatient service were also
analysed as a comparison. RESULTS: In total, 19 201 patients were referred to the
WRH neurosurgical service over the 10 years of the study. Within this timeframe,
7105 patients were referred by GPs and 12 096 were referred by specialist teams.
Only 348 patients (4.9%) referred by GPs underwent some form of therapeutic
intervention, compared to 3489 patients (28.8%) referred by specialist teams.
DISCUSSION: Our data shows that specialist referrals result in a proportionally
greater number of therapeutic interventions than GP referrals. This is in part
due to the wider array of diagnostic tests available to specialists compared to
GPs. The development of relevant guidelines for primary care referral to a
neurosurgical service appears warranted and could facilitate initiation of
appropriate investigations in primary care.
PMID- 26437044
TI - General practitioner awareness of sexual orientation among a community and
internet sample of gay and bisexual men in New Zealand.
AB - INTRODUCTION: General practitioners (GPs) can improve HIV and sexually
transmitted infection (STI) screening, vaccination and wellbeing among gay,
bisexual and other men who have sex with men (GBM) if they are aware of a
patient's sexual orientation. AIM: To estimate GP awareness of their GBM
patients' sexual orientation and examine whether HIV and STI screening was
associated with this. METHODS: We analysed anonymous, self-completed data from
3168 GBM who participated in the community-based Gay Auckland Periodic Sex Survey
(GAPSS) and Internet-based Gay men's Online Sex Survey (GOSS) in 2014.
Participants were asked if their usual GP was aware of their sexual orientation
or that they had sex with men. RESULTS: Half (50.5%) believed their usual GP was
aware of their sexual orientation/behaviour, 17.0% were unsure, and 32.6%
believed he/she was unaware. In multivariate analysis, GP awareness was
significantly lower if the respondent was younger, Asian or an 'Other' ethnicity,
bisexual-identified, had never had anal intercourse or had first done so very
recently or later in life, and had fewer recent male sexual partners. GBM whose
GP was aware of their sexual orientation were more likely to have ever had an HIV
test (91.5% vs 57.9%; p<0.001), specific STI tests (91.7% vs 68.9%; p<0.001), and
were twice as likely to have had an STI diagnosed. DISCUSSION: Lack of sexual
orientation disclosure is resulting in missed opportunities to reduce health
inequalities for GBM. More proactive, inclusive and safe environments surrounding
the care of sexual orientation minorities are needed in general practice to
encourage disclosure.
PMID- 26437045
TI - The patient perspective on a first raised PSA test.
AB - INTRODUCTION: Approximately 350 000 prostate-specific antigen (PSA) tests are
undertaken in New Zealand on a quarter of a million men each year. A number of
studies have looked at PSA testing done by general practitioners (GPs) and
subsequent outcomes. Few have looked at the patient perspective after a raised
PSA result. AIM: To explore patient experiences up to and following a raised PSA
test. METHODS: Thirty-one general practices within the Midland region were
recruited. Community laboratory databases were used to identify all men with a
first raised PSA test during 2010. Questionnaires were sent to these men.
RESULTS: One hundred and ninety-four (63%) eligible responses were received from
307 eligible men delivered questionnaires. For 54% of men this was their first
PSA test. Most men (66%) identified that their PSA test was initiated by their
GP. Forty-three percent of men identified having symptoms at the time of their
first raised PSA test. A digital rectal examination (DRE) was performed on 73% of
men at the time of the test. Fifty-eight percent of men were referred to see a
specialist. Maori men were less likely to be referred after a raised PSA. Of all
men referred, 61% received a biopsy. DISCUSSION: PSA testing is predominantly
initiated by GPs. We found the care pathway is variable for men after an elevated
PSA result. Standardisation of the pathway prior to and post diagnosis would
assist patients in knowing what to expect and would aid in GP management of men
being investigated for prostate cancer.
PMID- 26437046
TI - The impact of non-motor manifestations of Parkinson's disease on partners:
understanding and application of chronic sorrow theory.
AB - INTRODUCTION: Parkinson's disease (PD) can cause many emotions, including grief
and a sense of isolation for both the person with PD (referred to as
Parkinsonian) and their partner. Such ongoing grief and emotional turmoil can be
termed chronic sorrow. The aim of this research is to present accounts of
partners' perspectives, analysed in the context of chronic sorrow theory, to
offer health professionals an insight into the impact of non-motor PD symptoms on
partners. METHODS: A group of partners of Parkinsonians provided the data through
individual stories. These stories were subjected to thematic analysis, using a
seven-step process leading to the establishment of themes. FINDINGS: Caregiver
burden and chronic sorrow is not related to providing physical care, but the
emotional care of attempting to minimise the effect of PD, coping with
disturbance to sleep, and helping the Parkinsonian to maintain as much
independence as possible. Contributors to this article found chronic sorrow
theory provided a framework for understanding their emotions. Sharing their
experiences with others provided an opportunity to be heard, and enabled them to
make sense of individual situations. CONCLUSION: Chronic sorrow theory provides a
useful framework for both partners of Parkinsonians in understanding their
emotional responses, and for health professionals in considering the challenges
partners face in coping with living with a person with PD.
PMID- 26437047
TI - Culturally and linguistically diverse patients' views of multimorbidity and
general practice care.
AB - INTRODUCTION: It is recognised that patients who are culturally and
linguistically diverse (CALD) have challenges in accessing health care and
understanding health advice or instructions. Those with multimorbidity (MM) are
likely to have additional difficulties. In New Zealand, little is known about how
this patient group view their health and general practice health care. This study
examined the views of multimorbid CALD patients about MM and the health care
available in a Very Low Cost Access general practice. METHODS: This qualitative
study recruited Samoan, Cook Island Ma-ori , and Cambodian patients with diabetes
and more than three other long-term conditions. Two individual interviews and two
language-specific focus groups were undertaken to yield themes representing the
experience of these CALD patients with MM. FINDINGS: Participants described MM as
having considerable impact on their life. They reported feeling responsible for
supporting their own health and many detailed self-management techniques.
However, they also expressed confusion, lack of information and limited
understanding of MM, in particular about managing medication. Not all patients
were aware of the range of available general practice services and some described
difficulties in accessing general practice care. CONCLUSION: Despite being
motivated to self-manage, this patient group report challenges in understanding
their conditions and how to manage them, which may also be influenced by health
beliefs. Available general practice services are not well known by CALD patients
with MM. There is likely to be value in developing a specific structured, yet
patient-centred, model of care for this group of patients.
PMID- 26437048
TI - Nursing roles and responsibilities in general practice: three case studies.
AB - INTRODUCTION: Primary care nursing teams may now comprise registered nurses
(usually termed practice nurses), nurse practitioners, physician assistants,
enrolled nurses, and primary care practice assistants, clinical assistants, or
nursing assistants. There is a need to understand how practitioners in the
different roles work with patients in the changed environment. The aim of this
study was to describe the different configurations of health professionals' skill
mix in three dissimilar primary care practices, their inter- and intra
professional collaboration and communication, and to explore the potential of
expanded nursing scopes and roles to improve patient access. METHODS: Document
review, observation and interviews with key stakeholders were used to explore how
health practitioners in three practice settings work together, including their
delegation, substitution, enhancement and innovation in roles and
interdisciplinary interactions in providing patient care. A multiphase
integrative, qualitative and skill-mix framework analysis was used to compare
findings related to nursing skill-mix across case studies. FINDINGS: Three models
of primary care provision, utilising different nursing skill-mix and innovations
were apparent. These illustrate considerable flexibility and responsiveness to
local need and circumstances. CONCLUSION: Enabling nurses to work to the full
extent of their scope, along with some adjustments to the models of care, greater
multidisciplinary cooperation and coordination could mitigate future workforce
shortages and improve patient access to care.
PMID- 26437049
TI - Doctors' attitudes and confidence towards providing nutrition care in practice:
Comparison of New Zealand medical students, general practice registrars and
general practitioners.
AB - INTRODUCTION: Improvements in individuals' nutrition behaviour can improve risk
factors and outcomes associated with lifestyle-related chronic diseases. AIM:
This study describes and compares New Zealand medical students, general practice
registrars and general practitioners' (GPs') attitudes towards incorporating
nutrition care into practice, and self-perceived skills in providing nutrition
care. METHODS: A total of 183 New Zealand medical students, 51 general practice
registrars and 57 GPs completed a 60-item questionnaire investigating attitudes
towards incorporating nutrition care into practice and self-perceived skills in
providing nutrition care. Items were scored using a 5-point Likert scale. Factor
analysis was conducted to group questionnaire items and a generalised linear
model compared differences between medical students, general practice registrars
and GPs. RESULTS: All groups indicated that incorporating nutrition care into
practice is important. GPs displayed more positive attitudes than students
towards incorporating nutrition in routine care (p<0.0001) and performing
nutrition recommendations (p<0.0001). General practice registrars were more
positive than students towards performing nutrition recommendations (p=0.004),
specified practices (p=0.037), and eliciting behaviour change (p=0.024). All
groups displayed moderate confidence towards providing nutrition care. GPs were
more confident than students in areas relating to wellness and disease
(p<0.0001); macronutrients (p=0.030); micronutrients (p=0.010); and women,
infants and children (p<0.0001). DISCUSSION: New Zealand medical students,
general practice registrars and GPs have positive attitudes and moderate
confidence towards incorporating nutrition care into practice. It is possible
that GPs' experience providing nutrition care contributes to greater confidence.
Strategies to facilitate medical students developing confidence in providing
nutrition care are warranted.
PMID- 26437050
TI - General practitioners should allow use of anonymised patient records for
research: Yes.
PMID- 26437051
TI - General practitioners should allow use of anonymised patient records for
research: No. Confidentiality is not a decrepit concept.
PMID- 26437052
TI - Challenges in the doctor-patient relationship: 12 tips for more effective peer
group discussion.
AB - In New Zealand, almost all general practitioners are members of peer groups,
which provide opportunities for both clinical discussion and collegial support.
This article proposes that peer groups can also be a useful medium for exploring
specific challenges within the doctor-patient relationship. However, the peer
group culture needs to be receptive to this particular goal. Structured
discussion can help peer group members explore interpersonal issues more
thoroughly.
PMID- 26437054
TI - Effects of dry-aging on meat quality attributes and metabolite profiles of beef
loins.
AB - The objectives of this study were to evaluate different dry-aging regimes and
their impacts on quality attributes and metabolite profiles of beef loins. Thirty
loins (M. longissimus lumborum) from 15 beef carcasses at 2 days post-mortem were
obtained. Each loin was cut in half yielding 60 sections, which were randomly
assigned to six treatments including 4 dry-aging (2 temperatures (1 or 3 degrees
C) * 2 air-velocities (0.2 or 0.5 m/s)) and 2 wet-aging regimes for 3 weeks;
n=10/treatment. The sensory panel found that dry-aged loins had better flavour
and overall liking (P<0.05), but there were no differences in tenderness and
juiciness. No differences in drip/cook-loss and colour were observed. Metabolite
analysis showed that 7 metabolites, including several flavour precursors, were
more abundant in the dry-aged beef compared to the wet-aged beef, which may
contribute to the enhanced flavours of the dry-aged beef. Overall, dry-aging
loins at 3 degrees C with 0.2m/s resulted in the greatest improvement in beef
palatability.
PMID- 26437053
TI - A nanobuffer reporter library for fine-scale imaging and perturbation of
endocytic organelles.
AB - Endosomes, lysosomes and related catabolic organelles are a dynamic continuum of
vacuolar structures that impact a number of cell physiological processes such as
protein/lipid metabolism, nutrient sensing and cell survival. Here we develop a
library of ultra-pH-sensitive fluorescent nanoparticles with chemical properties
that allow fine-scale, multiplexed, spatio-temporal perturbation and
quantification of catabolic organelle maturation at single organelle resolution
to support quantitative investigation of these processes in living cells.
Deployment in cells allows quantification of the proton accumulation rate in
endosomes; illumination of previously unrecognized regulatory mechanisms coupling
pH transitions to endosomal coat protein exchange; discovery of distinct pH
thresholds required for mTORC1 activation by free amino acids versus proteins;
broad-scale characterization of the consequence of endosomal pH transitions on
cellular metabolomic profiles; and functionalization of a context-specific
metabolic vulnerability in lung cancer cells. Together, these biological
applications indicate the robustness and adaptability of this nanotechnology
enabled 'detection and perturbation' strategy.
PMID- 26437055
TI - Pain, Depression and Inflammation: Are Interconnected Causative Factors Involved?
AB - Co-morbid depression and chronic pain are highly prevalent. The purpose of this
review is to examine the role of chronic inflammation as a common mediator of
these co-morbidities. Dysfunctional bidirectional pathways between the brain and
the immune, endocrine and neurotransmitter systems have been extensively
described and implicated in pain and psychiatric disorders. This short review
therefore accesses the evidence in favour of the psychoneuroendocrine hypothesis
of psychiatric disorders under three main headings: (1) by illustrating how
different types of stress play a crucial role in initiating chronic inflammation
in major depression, (2) by accessing the evidence that pain is frequently an
important component of, and an initiator of, depression, and (3) considering the
evidence that chronic inflammation provides an important link between chronic
pain and depression, and the possible cellular mechanisms involved in this
process. By understanding the critical role that chronic inflammation plays in
pain and depression, novel approaches to the development of drugs may emerge that
offer improvements in treatment.
PMID- 26437056
TI - A randomized phase II study of stem cell mobilization with cyclophosphamide+G-CSF
or G-CSF alone after lenalidomide-based induction in multiple myeloma.
AB - The most common means of mobilizing autologous stem cells is G-CSF alone or
combined with cyclophosphamide (CY) to obtain sufficient CD34+ cells for one to
two transplants. There are few prospective, randomized studies investigating
mobilization regimens in multiple myeloma (MM), especially after lenalidomide
based induction. We designed this prospective, randomized study to compare low
dose CY 2 g/m2 +G-CSF (arm A) and G-CSF alone (arm B) after lenalidomide-based up
front induction in MM. Of the 80 initially randomized patients, 69 patients were
evaluable, 34 and 35 patients in arms A and B, respectively. The primary end
point was the proportion of patients achieving a yield of ?3 * 10(6)/kg CD34+
cells with 1-2 aphereses, which was achieved in 94% and 77% in arms A and B,
respectively (P=0.084). The median number of aphereses needed to reach the yield
of ?3 * 10(6)/kg was lower in arm A than in arm B (1 vs. 2, P=0.035). Two
patients needed plerixafor in arm A and five patients in arm B (P=0.428).
Although CY-based mobilization was more effective, G-CSF alone was successful in
a great majority of patients to reach the defined collection target after three
cycles of lenalidomide-based induction.
PMID- 26437057
TI - Second reduced intensity conditioning allogeneic transplant as a rescue strategy
for acute leukaemia patients who relapse after an initial RIC allogeneic
transplantation: analysis of risk factors and treatment outcomes.
AB - Limited therapeutic options are available after relapse of acute leukaemia
following first reduced intensity conditioning haematopoietic stem cell
transplantation (RIC1). A retrospective study on European Society for Blood and
Marrow Transplantation (EBMT) registry data was performed on 234 adult patients
with acute leukaemia who received a second RIC transplantation (RIC2) from 2000
to 2012 as a salvage treatment for relapse following RIC1. At the time of RIC2,
167 patients (71.4%) had relapsed or refractory disease, 49 (20.9%) were in
second CR and 18 (7.7%) in third or higher CR. With a median follow-up of 21 (1.5
79) months after RIC2, 51 patients are still alive. At 2 years, the cumulative
incidence of non-relapse mortality (NRM), relapse incidence (RI), leukaemia-free
survival (LFS) and overall survival (OS) were 22.4% (95% confidence interval
(CI): 17-28.4), 63.9% (56.7-70.1), 14.6% (8.8-18.5) and 20.5% (14.9-26.1),
respectively. In patients with acute myelogenous, biphenotypic and
undifferentiated leukaemia (representing 89.8% of all patients), duration of
remission following RIC1 >225 days, presence of CR at RIC2, patient's Karnofsky
performance status >80 at RIC2 and non-myeloablative conditioning were found to
be the strongest predictors of patients' favourable outcome.
PMID- 26437058
TI - Cerebrospinal fluid chimerism analysis in patients with neurological symptoms
after allogeneic cell transplantation.
AB - Central nervous system (CNS) complications have been described in patients
undergoing allogeneic hematopoietic cell transplantation (alloHCT). Cerebrospinal
fluid (CSF) analysis is included in the diagnostic workup in patients with
neurological symptoms after alloHCT. CSF donor-recipient chimerism analysis
usually is not used to evaluate patients with neurological complications after
alloHCT. To assess the potential contribution of CSF donor-recipient chimerism in
patients with neurological complications, we analyzed 85 CSF samples from 50
patients with neurological complications after alloHCT. After alloHCT, 21
patients showed the presence of recipient-derived DNA. In 13 of these patients,
recurrence of the underlying disease was detected in CSF. There was a moderate
correlation between the recipient DNA percentage as detected by short tandem
repeat (STR) amplification and the cell concentration in CSF (Spearmann r: 0.66
P=0.004). The percentage of cells with immunophenotypic abnormalities from
patients relapsing in the CNS detected by flow cytometry showed a strong
correlation with the percentage of recipient-derived DNA in CSF assessed by STR
analysis (Spearmann r: 0.83 P=0.0008). Donor-recipient chimerism analysis in CSF
in patients with neurological symptoms after alloHCT is a practical, feasible and
useful complementary method to the already established methodologies included in
the diagnostic workup.
PMID- 26437059
TI - The impact of pre-transplant body weight on short- and long-term outcomes after
allogeneic hematopoietic cell transplantation in adults using different weight
classification tools.
PMID- 26437060
TI - Long-term results of adjuvant donor lymphocyte transfusion in AML after
allogeneic stem cell transplantation.
AB - Adjuvant transfusion of donor lymphocytes (aDLT) may reduce the risk of relapse
after allogeneic stem cell transplantation in high-risk AML. We performed a
retrospective analysis on the safety and efficacy of aDLT in a cohort of 46
patients. To be eligible for aDLT, patients had to be in CR for at least 120 days
from transplantation, off immunosuppression for ?30 days and free of GvHD. Thirty
four patients with similar disease characteristics and fulfilling the same
selection criteria served as controls. Median follow-up among aDLT recipients was
7.2 years. Ten patients (22%) relapsed inspite of aDLT, as compared with 53% in
the control group. Induction of GvHD was the main complication. However, non
relapse mortality was low with patients dying from infection (n=2), severe
chronic GvHD (n=1) and secondary malignancy (n=2). At the time of analysis, 31/46
aDLT recipients were alive in CR at a median of 5.7 years after first aDLT.
Overall survival at 7 years after transplant was 67% as compared with 31% in the
control group (P<0.001). In conclusion, aDLT is safe, when given in escalating
doses to a well predefined group of patients. Long-term survival can be achieved.
PMID- 26437061
TI - Clinically significant adverse events after major ABO mismatch BMT.
PMID- 26437062
TI - Long-term survival outcomes of reduced-intensity allogeneic or autologous
transplantation in relapsed grade 3 follicular lymphoma.
AB - Grade 3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate
the optimal first transplantation approach in relapsed/refractory grade 3 FL
patients, we compared the long-term outcomes after allogeneic (allo-) vs
autologous hematopoietic cell transplantation (auto-HCT) in the rituximab era. A
total of 197 patients undergoing first reduced-intensity conditioning (RIC) allo
HCT or first auto-HCT during 2000-2012 were included. Rituximab-naive patients
were excluded. Allo-HCT recipients were younger, more heavily pretreated and had
a longer interval between diagnosis and HCT. The 5-year probabilities of non
relapse mortality (NRM), relapse/progression, PFS and overall survival (OS) for
auto-HCT vs allo-HCT groups were 4% vs 27% (P<0.001), 61% vs 20% (P<0.001), 36%
vs 51% (P=0.07) and 59% vs 54% (P=0.7), respectively. On multivariate analysis,
auto-HCT was associated with reduced risk of NRM (relative risk (RR)=0.20;
P=0.001). Within the first 11 months post HCT, auto- and allo-HCT had similar
risks of relapse/progression and PFS. Beyond 11 months, auto-HCT was associated
with higher risk of relapse/progression (RR=21.3; P=0.003) and inferior PFS
(RR=3.2; P=0.005). In the first 24 months post HCT, auto-HCT was associated with
improved OS (RR=0.42; P=0.005), but in long-time survivors (beyond 24 months) it
was associated with inferior OS (RR=3.6; P=0.04). RIC allo-HCT as the first
transplant approach can provide improved PFS and OS, in long-term survivors.
PMID- 26437063
TI - A randomized controlled trial of cyclosporine and tacrolimus with strict control
of blood concentrations after unrelated bone marrow transplantation.
AB - Previous studies have suggested that tacrolimus (TAC) is more potent than
cyclosporine (CSA) for prophylaxis against acute GVHD after allogeneic
hematopoietic stem cell transplantation (HSCT). However, the target blood
concentrations of these drugs in these studies were not consistent with the
current recommendations. Therefore, we performed a randomized controlled trial to
compare CSA and TAC with target blood concentrations of 500 and 15 ng/ml,
respectively, to prevent acute GVHD after unrelated HSCT. A total of 107 patients
were randomized into a CSA group (n=53) or a TAC group (n=54). During the first 4
weeks after HSCT, more than 90% of the patients achieved a mean blood
concentration of between 80 and 120% of the target concentration. The incidences
of grade II-IV and grade III-IV acute GVHD were 39.6 and 7.5% for the CSA group
and 33.3 and 9.4% for the TAC group, respectively (P=0.41 and P=0.76). Other
clinical outcomes, including overall survival, disease-free survival and the
incidences of relapse, non-relapse mortality, and organ toxicities, were also
equivalent. We concluded that the combinations of CSA and TAC with strict dose
adjustment showed similar efficacies and toxicities as prophylaxis against acute
GVHD after unrelated HSCT.
PMID- 26437064
TI - Influence of melphalan plus fludarabine-conditioning regimen in elderly patients
aged ?55 years with hematological malignancies.
PMID- 26437065
TI - Diffuse large B-cell lymphoma: is salvage possible after failure of second-line
treatment?
PMID- 26437066
TI - The bone marrow microenvironment is similarly impaired in allogeneic
hematopoietic stem cell transplantation patients with early and late poor graft
function.
AB - Poor graft function (PGF), including early and late PGF, is a serious
complication following allotransplant. We recently reported that bone marrow
microenvironment abnormalities may occur in cases of late PGF. Whether these
abnormalities occur in early PGF remains unknown. To answer this question, we
performed a nested case-control study comparing cellular elements of the bone
marrow microenvironment in 10 subjects with early PGF, 30 subjects with late PGF
and 40 subjects without PGF. Bone marrow endosteal cells, perivascular cells and
endothelial cells were analyzed by flow cytometry and by hematoxylin-eosin and
immunohistochemical staining in situ. Subjects with early and late PGF had
similar abnormalities in these cell types compared with transplant recipients
without PGF. However, none of the aforementioned elements of the bone marrow
microenvironment were significantly different between early and late PGF
patients. Our data suggest that similar abnormalities in the bone marrow
microenvironment may occur in early and late PGF post allotransplant. Cellular
approaches, such as the administration of mesenchymal stem cells, promise to be
beneficial therapeutic strategies in patients with early or late PGF.
PMID- 26437067
TI - Allogeneic hematopoietic cell transplantation for severe aplastic anemia: similar
long-term overall survival after transplantation with related donors compared to
unrelated donors.
PMID- 26437068
TI - Decreased pulmonary function in asymptomatic long-term survivors after allogeneic
hematopoietic stem cell transplant.
PMID- 26437069
TI - Exacerbation of IgA nephropathy following G-CSF administration for PBSC
collection: suggestions for better donor screening.
PMID- 26437070
TI - Physician-diagnosed depression and suicides in pediatric hematopoietic cell
transplant survivors with up to 40 years of follow-up.
PMID- 26437071
TI - Early post-transplant contrast-enhanced abdominopelvic CT scan predicts the risk
of subsequent acute GvHD.
PMID- 26437072
TI - Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced
Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass
Index.
AB - INTRODUCTION: Body composition has emerged as a prognostic factor in cancer
patients. We investigated whether sarcopenia at diagnosis and loss of skeletal
muscle during palliative chemotherapy were associated with survival in patients
with pancreatic cancer. METHODS: We retrospectively reviewed the clinical
outcomes of pancreatic cancer patients receiving palliative chemotherapy between
2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed
tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a
skeletal muscle index (SMI)< 42.2 cm2/m2 (male) and < 33.9 cm2/m2 (female) using
ROC curve. RESULTS: Among 484 patients, 103 (21.3%) patients were sarcopenic at
diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male
and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in
149 patients (37.3%), with no gender difference. By multivariate analysis,
sarcopenia (P< 0.001), decreasedBMI and SMI during chemotherapy (P = 0.002, P =
0.004, respectively) were poor prognostic factors for overall survival (OS).
While the OS of male patients was affected with sarcopenia (P< 0.001) and
decreased SMI (P = 0.001), the OS of female patients was influenced with
overweight at diagnosis (P = 0.006), decreased BMI (P = 0.032) and decreased SMI
(P = 0.014). Particularly, while the change of BMI during chemotherapy did not
have impact on OS within the patients with maintained SMI (P = 0.750), decrease
in SMI was associated with poor OS within the patients with maintained BMI (HR
1.502; P = 0.002). CONCLUSIONS: Sarcopenia at diagnosis and depletion of skeletal
muscle, independent of BMI change, during chemotherapy were poor prognostic
factors in advanced pancreatic cancer.
PMID- 26437073
TI - Verbal Short-Term Memory Deficits in Chinese Children with Dyslexia may not be a
Problem with the Activation of Phonological Representations.
AB - This study explored the underlying mechanism of the verbal short-term memory
deficit in Chinese children with developmental dyslexia. Twenty-four children
with dyslexia and 28 age-matched normal readers participated in the study. They
were required to memorize a visually presented series of six Chinese characters
and identify them from a list also including code-specific distracters and non
code-specific distracters. Error rates were recorded and were higher for code
specific distracters in all three conditions, revealing phonological, visual, and
semantic similarity effects respectively. Group comparisons showed a stronger
phonological similarity effect in dyslexic group, suggesting intact activation of
phonological representations of target characters. Children with dyslexia also
exhibited a greater semantic similarity effect, revealing stronger activation of
semantic representations, while visual similarity effects were equivalent to
controls. These results suggest that the verbal short-term memory deficit in
Chinese dyslexics might not stem from insufficient activation of phonological
information. Based the semantic activation of target characters in dyslexics is
greater than in controls, it is possible that the memory deficit of dyslexia is
related with deficient inhibition of target semantic representations in short
term memory.
PMID- 26437074
TI - First fetal case of the 8q24.3 contiguous genes syndrome.
AB - Molecular cytogenetics, particularly array-CGH, opened the way to the " genotype
first approach " and for the discovery of new micro rearrangement syndromes. This
was the case for the 8q24.3 microdeletion syndrome. Here, we describe the
phenotype of a fetus with a 8q24.3 deletion. This rare condition has to be
considered as a contiguous genes syndrome because its phenotype is generated by
the SCRIB and PUF60 adjacent gene endophenotypes. The fetus presented
atrioventricular septal defect and hypoplastic aortic arch, facial dysmorphism,
microretrognathia, dysmorphic ears, clinodactyly of the 5th digit on both hands,
mild rocker bottom feet and abnormal third sacral vertebra. This fetus is the
first case where the endophenotype produced by SCRIB gene is absent. This case is
compared with the previous published cases.
PMID- 26437075
TI - Assessing the Power of Exome Chips.
AB - Genotyping chips for rare and low-frequent variants have recently gained
popularity with the introduction of exome chips, but the utility of these chips
remains unclear. These chips were designed using exome sequencing data from
mainly American-European individuals, enriched for a narrow set of common
diseases. In addition, it is well-known that the statistical power of detecting
associations with rare and low-frequent variants is much lower compared to
studies exclusively involving common variants. We developed a simulation program
adaptable to any exome chip design to empirically evaluate the power of the exome
chips. We implemented the main properties of the Illumina HumanExome BeadChip
array. The simulated data sets were used to assess the power of exome chip based
studies for varying effect sizes and causal variant scenarios. We applied two
widely-used statistical approaches for rare and low-frequency variants, which
collapse the variants into genetic regions or genes. Under optimal conditions, we
found that a sample size between 20,000 to 30,000 individuals were needed in
order to detect modest effect sizes (0.5% < PAR > 1%) with 80% power. For small
effect sizes (PAR <0.5%), 60,000-100,000 individuals were needed in the presence
of non-causal variants. In conclusion, we found that at least tens of thousands
of individuals are necessary to detect modest effects under optimal conditions.
In addition, when using rare variant chips on cohorts or diseases they were not
originally designed for, the identification of associated variants or genes will
be even more challenging.
PMID- 26437076
TI - Screening for the Most Suitable Reference Genes for Gene Expression Studies in
Equine Milk Somatic Cells.
AB - Apart from the well-known role of somatic cell count as a parameter reflecting
the inflammatory status of the mammary gland, the composition of cells isolated
from milk is considered as a valuable material for gene expression studies in
mammals. Due to its unique composition, in recent years an increasing interest in
mare's milk consumption has been observed. Thus, investigating the genetic
background of horse's milk variability presents and interesting study model.
Relying on 39 milk samples collected from mares representing three breeds (Polish
Primitive Horse, Polish Cold-blooded Horse, Polish Warmblood Horse) we aimed to
investigate the utility of equine milk somatic cells as a source of mRNA and to
screen the best reference genes for RT-qPCR using geNorm and NormFinder
algorithms. The results showed that despite relatively low somatic cell counts in
mare's milk, the amount and the quality of the extracted RNA are sufficient for
gene expression studies. The analysis of the utility of 7 potential reference
genes for RT-qPCR experiments for the normalization of equine milk somatic cells
revealed some differences between the outcomes of the applied algorithms,
although in both cases the KRT8 and TOP2B genes were pointed as the most stable.
Analysis by geNorm showed that the combination of 4 reference genes (ACTB, GAPDH,
TOP2B and KRT8) is required for apropriate RT-qPCR experiments normalization,
whereas NormFinder algorithm pointed the combination of KRT8 and RPS9 genes as
the most suitable. The trial study of the relative transcript abundance of the
beta-casein gene with the use of various types and numbers of internal control
genes confirmed once again that the selection of proper reference gene
combinations is crucial for the final results of each real-time PCR experiment.
PMID- 26437077
TI - Analysing Local Sparseness in the Macaque Brain Network.
AB - Understanding the network structure of long distance pathways in the brain is a
necessary step towards developing an insight into the brain's function,
organization and evolution. Dense global subnetworks of these pathways have often
been studied, primarily due to their functional implications. Instead we study
sparse local subnetworks of the pathways to establish the role of a brain area in
enabling shortest path communication between its non-adjacent topological
neighbours. We propose a novel metric to measure the topological communication
load on a vertex due to its immediate neighbourhood, and show that in terms of
distribution of this local communication load, a network of Macaque long distance
pathways is substantially different from other real world networks and random
graph models. Macaque network contains the entire range of local subnetworks,
from star-like networks to clique-like networks, while other networks tend to
contain a relatively small range of subnetworks. Further, sparse local
subnetworks in the Macaque network are not only found across topographical super
areas, e.g., lobes, but also within a super-area, arguing that there is
conservation of even relatively short-distance pathways. To establish the
communication role of a vertex we borrow the concept of brokerage from social
science, and present the different types of brokerage roles that brain areas
play, highlighting that not only the thalamus, but also cingulate gyrus and
insula often act as "relays" for areas in the neocortex. These and other analysis
of communication load and roles of the sparse subnetworks of the Macaque brain
provide new insights into the organisation of its pathways.
PMID- 26437078
TI - Novel Mn3 [Co(CN)6]2@SiO2@Ag Core-Shell Nanocube: Enhanced Two-Photon
Fluorescence and Magnetic Resonance Dual-Modal Imaging-Guided Photothermal and
Chemo-therapy.
AB - The versatile Mn3[Co(CN)6]2@SiO2@Ag core-shell NCs are prepared by a simple
coprecipitation method. Ag nanoparticles with an average diameter of 12 nm
deposited on the surface of Mn3[Co(CN)6]2@SiO2 through S-Ag bonding are
fabricated in ethanol solution by reducing silver nitrate (AgNO3 ) with NaBH4 .
The NCs possess T1 -T2 dual-modal magnetic resonance imaging ability. The inner
Prussian blue analogs (PBAs) Mn3[Co(CN)6]2 exhibit bright two-photon fluorescence
(TPF) imaging when excited at 730 nm. Moreover, the TPF imaging intensity
displays 1.85-fold enhancement after loading of Ag nanoparticles. Besides, the
sample also has multicolor fluorescence imaging ability under 403, 488, and 543
nm single photon excitation. The as-synthesized Mn3[Co(CN)6]2@SiO2@Ag NCs show a
DOX loading capacity of 600 mg g(-1) and exhibit an excellent ability of near
infrared (NIR)-responsive drug release and photothermal therapy (PTT) which is
induced from the relative high absorbance in NIR region. The combined
chemotherapy and PTT against cancer cells in vitro test shows high therapeutic
efficiency. The multimodal treatment and imaging could lead to this material a
potential multifunctional system for biomedical diagnosis and therapy.
PMID- 26437079
TI - The SET Domain Is Essential for Metnase Functions in Replication Restart and the
5' End of SS-Overhang Cleavage.
AB - Metnase (also known as SETMAR) is a chimeric SET-transposase protein that plays
essential role(s) in non-homologous end joining (NHEJ) repair and replication
fork restart. Although the SET domain possesses histone H3 lysine 36
dimethylation (H3K36me2) activity associated with an improved association of
early repair components for NHEJ, its role in replication restart is less clear.
Here we show that the SET domain is necessary for the recovery from DNA damage at
the replication forks following hydroxyurea (HU) treatment. Cells overexpressing
the SET deletion mutant caused a delay in fork restart after HU release. Our In
vitro study revealed that the SET domain but not the H3K36me2 activity is
required for the 5' end of ss-overhang cleavage with fork and non-fork DNA
without affecting the Metnase-DNA interaction. Together, our results suggest that
the Metnase SET domain has a positive role in restart of replication fork and the
5' end of ss-overhang cleavage, providing a new insight into the functional
interaction of the SET and the transposase domains.
PMID- 26437081
TI - Oral Health-Related Quality of Life and Self-Rated Speech in Children With
Existing Fistulas in Mid-Childhood and Adolescence.
AB - OBJECTIVE: To report the associations of oro-nasal fistulae on the patient
centered outcomes oral health-related quality of life and self-reported speech
outcomes in school aged-children. DESIGN: Prospective, nonrandomized multicenter
design. SETTING: Six ACPA-accredited cleft centers. PARTICIPANTS: Patients with
cleft palate at the age of mixed dentition. INTERVENTIONS: None. MAIN OUTCOME
MEASURES: Prevalence of fistula and location of fistula (Pittsburgh
Classification System). Patients were placed into one of three groups based on
the following criteria: alveolar cleft present, no previous repair (Group 1);
alveolar cleft present, previously repaired (Group 2); no congenital alveolar
cleft (Group 3). Presence of fistula and subgroup classification were correlated
to oral health-related quality of life (Child Oral Health Impact Profile [COHIP])
and perceived speech outcomes. RESULTS: The fistula rate was 5.52% (62 of 1198
patients). There was a significant difference in fistula rate between the three
groups: Group 1 (11.15%), Group 2 (4.44%), Group 3 (1.90%). Patients with fistula
had significantly lower COHIP scores (F1,1188 = 4.79; P = .03) and worse self
reported speech scores (F1,1197 = 4.27; P = .04). Group 1 patients with fistula
had the lowest COHIP scores (F5,1188 = 4.78, P =.02) and the lowest speech scores
(F5,1188 = 3.41, P = .003). CONCLUSIONS: Presence of palatal fistulas was
associated with lower oral health-related quality of life and perceived speech
among youth with cleft. The poorest outcomes were reported among those with the
highest fistula rates, including an unrepaired alveolar cleft.
PMID- 26437080
TI - Diffuse large B-cell lymphoma cell-of-origin classification using the Lymph2Cx
assay in the context of BCL2 and MYC expression status.
PMID- 26437082
TI - The Psychosocial Impact of Cleft Lip and/or Palate on Unaffected Siblings.
AB - BACKGROUND: Sibling relationships are among the most unique social connections,
significantly affecting psychosocial adjustment. Previous reviews in the fields
of chronic illness and disability have concluded that unaffected siblings of
children with long-term conditions are at risk of poorer psychological
functioning as a consequence. Much research has investigated the psychosocial
impact of CL/P on affected individuals and their parents, yet comparatively
little is known about the impact on other close family members. OBJECTIVE: To
gain a better understanding of the experience of unaffected siblings of children
born with CL/P, with a view to informing service provision and support. DESIGN:
Individual qualitative interviews conducted over the telephone/Internet with five
siblings and eight parents, including five sibling-parent pairs from the same
family. RESULTS: Thematic analysis identified three key themes applicable across
both parent and sibling interviews: perceptions of positive and negative impacts,
factors affecting the degree of impact, and support for families. CONCLUSIONS:
This study provides insight into a population that is often overlooked in the
context of cleft care. The analysis identified a number of sibling support and
information needs, along with suggestions of how to incorporate support for
siblings in practice. The findings suggest that an inclusive approach to health
care encompassing all members of the family is essential for optimal familial
adjustment.
PMID- 26437084
TI - A Young and Gifted Scientist.
PMID- 26437085
TI - Meta-Analysis of Soybean-based Biodiesel.
AB - Biofuel policy changes in the United States have renewed interest in soybean [
(L.) Merr.] biodiesel. Past studies with varying methodologies and functional
units can provide valuable information for future work. A meta-analysis of nine
peer-reviewed soybean life cycle analysis (LCA) biodiesel studies was conducted
on the northern Great Plains in the United States. Results of LCA studies were
assimilated into a standardized system boundary and functional units for global
warming (GWP), eutrophication (EP), and acidification (AP) potentials using
biodiesel conversions from peer-reviewed and government documents. Factors not
fully standardized included variations in NO accounting, mid- or end-point
impacts, land use change, allocation, and statistical sampling pools. A state-by
state comparison of GWP lower and higher heating values (LHV, HHV) showed
differences attributable to variations in spatial sampling and agricultural
practices (e.g., tillage, irrigation). The mean GWP of LHV was 21.1 g.CO-eq MJ
including outliers, and median EP LHV and AP LHV was 0.019 g.PO-eq MJ and 0.17
g.SO-eq MJ, respectively, using the limited data available. An LCA case study of
South Dakota soybean-based biodiesel production resulted in GWP estimates (29 or
31 g.CO-eq MJ; 100% mono alkyl esters [first generation] biodiesel or 100% fatty
acid methyl ester [second generation] biodiesel) similar to meta-analysis results
(30.1 g.CO-eq MJ). Meta-analysis mean results, including outliers, resemble the
California Low Carbon Fuel Standard for soybean biodiesel default value without
land use change of 21.25 g.CO-eq MJ. Results were influenced by resource
investment differences in water, fertilizer (e.g., type, application), and
tillage. Future biofuel LCA studies should include these important factors to
better define reasonable energy variations in regional agricultural management
practices.
PMID- 26437083
TI - New insights into the impact of Lactobacillus population on host-bacteria
metabolic interplay.
AB - We aimed at evaluating the association between intestinal Lactobacillus sp.
composition and their metabolic activity with the host metabolism in adult and
elderly individuals. Faecal and plasma metabolites were measured and correlated
to the Lactobacillus species distribution in healthy Estonian cohorts of adult (n
= 16; < 48 y) and elderly (n = 33; > 65 y). Total cholesterol, LDL, C-reactive
protein and glycated hemoglobin were statistically higher in elderly, while
platelets, white blood cells and urinary creatinine were higher in adults. Aging
was associated with the presence of L. paracasei and L. plantarum and the absence
of L. salivarius and L. helveticus. High levels of intestinal Lactobacillus sp.
were positively associated with increased concentrations of faecal short chain
fatty acids, lactate and essential amino acids. In adults, high red blood cell
distribution width was positively associated with presence of L. helveticus and
absence of L. ruminis. L. helveticus was correlated to lactate and butyrate in
faecal waters. This indicates a strong relationship between the composition of
the gut Lactobacillus sp. and host metabolism. Our results confirm that aging is
associated with modulations of blood biomarkers and intestinal Lactobacillus
species composition. We identified specific Lactobacillus contributions to gut
metabolic environment and related those to blood biomarkers. Such associations
may prove useful to decipher the biological mechanisms underlying host-gut
microbial metabolic interactions in an ageing population.
PMID- 26437086
TI - The Pivotal Role of Phosphorus in a Resilient Water-Energy-Food Security Nexus.
AB - We make the case that phosphorus (P) is inextricably linked to an increasingly
fragile, interconnected, and interdependent nexus of water, energy, and food
security and should be managed accordingly. Although there are many other drivers
that influence water, energy, and food security, P plays a unique and under
recognized role within the nexus. The P paradox derives from fundamental
challenges in meeting water, energy, and food security for a growing global
population. We face simultaneous dilemmas of overcoming scarcity of P to sustain
terrestrial food and biofuel production and addressing overabundance of P
entering aquatic systems, which impairs water quality and aquatic ecosystems and
threatens water security. Historical success in redistributing rock phosphate as
fertilizer to enable modern feed and food production systems is a grand societal
achievement in overcoming inequality. However, using the United States as the
main example, we demonstrate how successes in redistribution of P and
reorganization of farming systems have broken local P cycles and have
inadvertently created instability that threatens resilience within the nexus.
Furthermore, recent expansion of the biofuels sector is placing further pressure
on P distribution and availability. Despite these challenges, opportunities exist
to intensify and expand food and biofuel production through recycling and better
management of land and water resources. Ultimately, a strategic approach to
sustainable P management can help address the P paradox, minimize tradeoffs, and
catalyze synergies to improve resilience among components of the water, energy,
and food security nexus.
PMID- 26437087
TI - Dietary Nitrate for Methane Mitigation Leads to Nitrous Oxide Emissions from
Dairy Cows.
AB - Nitrate supplements to cattle diets can reduce enteric CH emissions. However, if
NO metabolism stimulates NO emissions, the effectiveness of dietary NO for CH
mitigation will be reduced. We quantified NO emissions as part of a dairy cow
feeding experiment in which urea was substituted in nearly iso-N diets with 0, 5,
14 or 21 g NO kg dry matter (DM). The feeding experiment was a Latin square with
repetition of Period 1. Each period lasted 4 wk, with CH emission measurements in
Week 4 using respiration chambers. During Period 3, NO concentrations in chamber
outlet air were monitored semicontinuously during 48 h. High, but fluctuating, NO
concentrations were seen at the two highest NO levels (up to between 2 and 5 MUL
L), and dynamics were linked with recent feed intake. In Periods 4 and 5, NO
concentrations and feed intake were determined from all four respiration chambers
during two 7-h periods. Emissions of NO coincided with feed intake, again with NO
concentrations in the microliter per liter range at the two highest NO intake
levels. Neither feed nor excretion of NO via urine were significant sources of
NO, indicating that emissions came from the animals. Leakages due to rumen
fistulation could also not account for NO emissions. The possibility that NO is
produced in the oral cavity is discussed. Nitrous oxide emission factors ranged
between 0.7 and 1.0% except in one case at 21 g NO kg DM, where it was 3.4%. When
accounting for NO emissions at the highest NO intake level, the overall GHG
mitigation effect in two different animal-diet combinations changed from -47 to
40%, and from -19 to -17%, respectively, due to NO emissions.
PMID- 26437088
TI - Methane and Nitrous Oxide Emissions from Flooded Rice Systems following the End
of-Season Drain.
AB - Large CH and NO fluxes can occur from flooded rice ( L.) systems following end-of
season drainage, which contribute significantly to the total growing-season
greenhouse gas (GHG) emissions. Field and laboratory studies were conducted to
determine under what soil water conditions these emissions occur. In three field
studies, GHG fluxes and dissolved CH in the soil pore water were measured before
and after drainage. Across all fields, approximately 10% of the total seasonal CH
emissions and 27% of the total seasonal NO emissions occurred following the final
drain, confirming the importance of quantifying postdrainage CH and NO emissions.
Preplant fertilizer N had no effect on CH emissions or dissolved CH; however,
increased postdrainage NO fluxes were observed at higher N rates. To determine
when postdrainage sampling needs to take place, our laboratory incubation study
measured CH and NO fluxes from intact soil cores from these fields as the soil
dried. Across fields, maximum CH emissions occurred at approximately 88% water
filled pore space (WFPS), but emissions were observed between 47 and 156% WFPS.
In contrast, maximum NO emissions occurred between 45 and 71% WFPS and were
observed between 16 and 109% WFPS. For all fields, gas samplings between 76 and
100% WFPS for CH emissions and between 43 and 78% WFPS for NO emissions was
necessary to capture 95% of these postdrainage emissions. We recommend that
frequent gas sampling following drainage be included in the GHG protocol of total
GHG emissions.
PMID- 26437089
TI - Soil Methane and Carbon Dioxide Fluxes from Cropland and Riparian Buffers in
Different Hydrogeomorphic Settings.
AB - Riparian buffers contribute to the mitigation of nutrient pollution in
agricultural landscapes, but there is concern regarding their potential to be hot
spots of greenhouse gas production. This study compared soil CO and CH fluxes in
adjacent crop fields and riparian buffers (a flood-prone forest and a flood
protected grassland along an incised channel) and examined the impact of water
table depth (WTD) and flood events on the variability of gas fluxes in riparian
zones. Results showed significantly ( < 0.001) higher CO emission in riparian
areas than in adjoining croplands (6.8 +/- 0.6 vs. 3.6 +/- 0.5 Mg CO-C ha yr;
mean +/- SE). Daily flux of CO and soil temperature were significantly related (
< 0.002), with Q values ranging between 1.75 and 2.53. Significant relationships
( < 0.05) were found between CH daily flux and WTD. Flood events resulted in
enhanced CH emission (up to +44.5 mg CH-C m d in a swale) under warm soil
conditions (>22 degrees C), but the effect of flooding was less pronounced in
early spring (emission <1.06 mg CH-C m d), probably due to low soil temperature.
Although CH flux direction alternated at all sites, overall the croplands and the
flood-affected riparian forest were CH sources, with annual emission averaging
+0.04 +/- 0.17 and +0.92 +/- 1.6 kg CH-C ha, respectively. In the riparian
forest, a topographic depression (<8% of the total area) accounted for 78% of the
annual CH emission, underscoring the significance of landscape heterogeneity on
CH dynamics in riparian buffers. The nonflooded riparian grassland, however, was
a net CH sink (-1.08 +/- 0.22 kg CH-C ha yr), probably due to the presence of
subsurface tile drains and a dredged/incised channel at that study site. Although
these hydrological alterations may have contributed to improvement in the CH sink
strength of the riparian grassland, this must be weighed against the water
quality maintenance functions and other ecological services provided by riparian
buffers.
PMID- 26437090
TI - Simulation of Birch and Pine Litter Influence on Early Stage of Reclaimed Soil
Formation Process under Controlled Conditions.
AB - The impact of litter decomposition on chemical substrate properties and element
leaching during early soil formation in afforested post-mine sites and the
influence of different tree species are key issues in new ecosystem development.
Scots pine ( L.) and common birch ( Roth) are important pioneering species used
in afforestation of post-mine sites in central and eastern Europe. The aim of
this study was to assess the impact of litter decomposition of these species on
the chemical properties of mine soil substrates. The impact of litter
decomposition on soil properties was tested on quaternary and neogene substrates
with different textures (sands, loams, and mixtures of clays and sands) in a
controlled incubation experiment using PVC columns. Simulation of precipitation
and leaching was undertaken for 10 wk at a temperature of 16 degrees C with
distilled water (200 mL wk) through cylinders with litter, substrate + litter,
and control substrate (no litter). Filtrated water solution was collected once a
week for laboratory analysis, and the concentrations of dissolved organic C,
total N, K, Ca, Mg, and P were determined. The study results indicate a stronger
impact of the common birch on the chemical properties of reclaimed mine soils
compared with pine. After the experiment, birch litter caused significant changes
in pH in quaternary sands, concentration of P in quaternary loams (Ql) and
mixtures of neogene clays and quaternary sands (QsNc), exchangeable Ca in QsNc,
and Mg in Ql and QsNc compared with pine litter. Birch, in comparison to pine,
may affect the intensity of early-stage soil-forming processes by increasing
nutrient availability and transport into the soil profile, which may affect the
development of soil microbial communities. This process results in different soil
properties under the two tree species.
PMID- 26437091
TI - Sensitivity Analysis of the Agricultural Policy/Environmental eXtender (APEX) for
Phosphorus Loads in Tile-Drained Landscapes.
AB - Numerical modeling is an economical and feasible approach for quantifying the
effects of best management practices on dissolved reactive phosphorus (DRP)
loadings from agricultural fields. However, tools that simulate both surface and
subsurface DRP pathways are limited and have not been robustly evaluated in tile
drained landscapes. The objectives of this study were to test the ability of the
Agricultural Policy/Environmental eXtender (APEX), a widely used field-scale
model, to simulate surface and tile P loadings over management, hydrologic,
biologic, tile, and soil gradients and to better understand the behavior of P
delivery at the edge-of-field in tile-drained midwestern landscapes. To do this,
a global, variance-based sensitivity analysis was performed, and model outputs
were compared with measured P loads obtained from 14 surface and subsurface edge
of-field sites across central and northwestern Ohio. Results of the sensitivity
analysis showed that response variables for DRP were highly sensitive to coupled
interactions between presumed important parameters, suggesting nonlinearity of
DRP delivery at the edge-of-field. Comparison of model results to edge-of-field
data showcased the ability of APEX to simulate surface and subsurface runoff and
the associated DRP loading at monthly to annual timescales; however, some high
DRP concentrations and fluxes were not reflected in the model, suggesting the
presence of preferential flow. Results from this study provide new insights into
baseline tile DRP loadings that exceed thresholds for algal proliferation.
Further, negative feedbacks between surface and subsurface DRP delivery suggest
caution is needed when implementing DRP-based best management practices designed
for a specific flow pathway.
PMID- 26437092
TI - Uncovering the Minor Contribution of Land-Cover Change in Upland Forests to the
Net Carbon Footprint of a Boreal Hydroelectric Reservoir.
AB - Hydropower in boreal conditions is generally considered the energy source
emitting the least greenhouse gas per kilowatt-hour during its life cycle. The
purpose of this study was to assess the relative contribution of the land-use
change on the modification of the carbon sinks and sources following the flooding
of upland forested territories to create the Eastmain-1 hydroelectric reservoir
in Quebec's boreal forest using Carbon Budget Model of the Canadian Forest
Sector. Results suggest a carbon sink loss after 100 yr of 300,000 +/- 100,000 Mg
CO equivalents (COe). A wildfire sensitivity analysis revealed that the ecosystem
would have acted as a carbon sink as long as <75% of the territory had burned
over the 100-yr-long period. Our long-term net carbon flux estimate resulted in
emissions of 4 +/- 2 g COe kWh as a contribution to the carbon footprint
calculation, one-eighth what was obtained in a recent study that used less
precise and less sensitive estimates. Consequently, this study significantly
reduces the reported net carbon footprint of this reservoir and reveals how
negligible the relative contribution of the land-use change in upland forests to
the total net carbon footprint of a hydroelectric reservoir in the boreal zone
can be.
PMID- 26437093
TI - Sludge-Derived Biochar for Arsenic(III) Immobilization: Effects of Solution
Chemistry on Sorption Behavior.
AB - Recycling sewage sludge by pyrolysis has attracted increasing attention for
pollutant removal from wastewater and soils. This study scrutinized As(III)
sorption behavior on sludge-derived biochar (SDBC) under different pyrolysis
conditions and solution chemistry. The SDBC pyrolyzed at a higher temperature
showed a lower As(III) sorption capacity and increasingly nonlinear isotherm due
to loss of surface sites and deoxygenation-dehydrogenation. The Langmuir sorption
capacity on SDBC (3.08-6.04 mg g) was comparable to other waste-derived sorbents,
with the highest As(III) sorption on SDBC pyrolyzed at 400 degrees C for 2 h. The
As(III) sorption kinetics best fit with the pseudo-second-order equation, thus
suggesting the significance of the availability of surface sites and initial
concentration. Sorption of As(III) was faster than that of Cr(VI) but slower than
that of Pb(II), which was attributed to their differences in molar volume
(correlated to diffusion coefficients) and sorption mechanisms. The X-ray
photoelectron spectra revealed an increase of oxide oxygen (O) with a decrease of
sorbed water, indicative of ligand exchange with hydroxyl groups on SDBC
surfaces. The As(III) sorption was not pH dependent in acidic-neutral range (pH <
8) due to the buffering capacity and surface characteristics of the SDBC;
however, sorption was promoted by increasing pH in the alkaline range (pH > 8)
because of As(III) speciation in solution. An increasing ionic strength (0.001
0.1 mol L) facilitated As(III) sorption, indicating the predominance of ligand
exchange over electrostatic interactions, while high concentrations (0.1 mol L)
of competing anions (fluoride, sulfate, carbonate, and phosphate) inhibited
As(III) sorption. These results suggest that SDBC is applicable for As(III)
immobilization in most environmentally relevant conditions.
PMID- 26437094
TI - Phosphate Treatment of Lead-Contaminated Soil: Effects on Water Quality, Plant
Uptake, and Lead Speciation.
AB - Water quality threats associated with using phosphate-based amendments to
remediate Pb-contaminated soils are a concern, particularly in riparian areas.
This study investigated the effects of P application rates to a Pb-contaminated
alluvial soil on Pb and P loss via surface water runoff, Pb accumulation in tall
fescue ( Schreb; Kentucky 31), and Pb speciation. An alluvial soil was treated
with triple superphosphate at P to Pb molar ratios of 0:1 (control), 4:1, 8:1,
and 16:1. After a 6-mo reaction period, rainfall simulation (RFS) studies were
conducted, followed by tall fescue establishment and a second set of RFS studies
(1 yr after treatment). Results from the first RFS study (unvegetated)
demonstrated that the total Pb and P concentrations in the effluents of 8:1 and
16:1 (P:Pb molar ratio) treatment levels were significantly greater ( < 0.05)
than the control. One year after P treatment and 6 mo after vegetation
establishment, total P and Pb concentrations of the effluents from a second RFS
decreased by one to three orders of magnitude. Total and dissolved P
concentration in runoff from the 16:1 P:Pb treatment remained significantly
greater than all other treatments. However, total Pb concentration in the runoff
was comparable among the treatments. Phosphorus treatment also reduced Pb uptake
into tall fescue by >55%. X-ray absorption near-edge structure spectroscopy data
showed that pyromorphite [Pb(PO)OH,Cl,F] abundance ranged from 0% (control) to
32% (16:1 P:Pb; 1 yr after treatment) of the total soil Pb. Although P treatment
stimulated pyromorphite formation, pyromorphite abundance was comparable between
the P-treated soils. These findings suggest that a 4:1 (P:Pb molar ratio) P
treatment may be a sufficient means of reducing Pb bioavailability while
minimizing concerns related to P loss in an alluvial setting.
PMID- 26437095
TI - Nitrogen Runoff Losses during Warm-Season Turfgrass Sod Establishment.
AB - Concern exists over the potential loss of nitrogen (N) and phosphorus (P) in
runoff from newly established and fertilized lawns. Nutrient losses can be higher
from turf when shoot density and surface cover are low and root systems are not
fully developed. This study was conducted to evaluate fertilizer source and
timing effects on nutrient losses from newly sodded lawns of St. Augustinegrass [
(Walt.) Kuntze]. For each study, 12 33.6-m plots were established on an
undisturbed Alfisol having a 3.7% slope. Each plot was equipped with a runoff
collection system, instrumentation for runoff flow rate measurement, and
automated samplers. A 28-d establishment study was initiated on 8 Aug. 2012 and
repeated on 9 Sept. 2012. Treatments included unfertilized plots, fertilized
plots receiving 4.88 g N m as urea 6 d after planting, fertilized plots receiving
4.88 g N m as sulfur-coated urea 6 d after planting, and fertilized plots
receiving 4.88 g N m as urea 19 d after planting. Runoff events were created by
irrigating with 17 mm of water over 27 min. Runoff water samples were collected
after every 37.8 L and analyzed for NO-N, NH-N, dissolved organic N (DON), and PO
P. Increases of approximately 2 to 4 mg L NO-N and 8 to 12 mg L PO-P occurred in
runoff 1 d after fertilization, which returned to background levels within 7 d.
Total fertilizer N lost to runoff was 0.6 to 4.2% of that applied. Delaying
fertilizer application until 19 d after planting provided no reduction in
nutrient loss compared with a similar application 6 d after planting.
Approximately 33% of the N lost in runoff was as DON. This large amount of DON
suggests significant N loss from decomposing organic matter may occur during sod
establishment.
PMID- 26437096
TI - Patch-Burn Grazing Effects on the Ecological Integrity of Tallgrass Prairie
Streams.
AB - Conversion to agriculture, habitat fragmentation, and the loss of native grazers
have made tallgrass prairie one of the most endangered ecosystems. One management
option for the remaining prairie parcels, patch-burn grazing (PBG), applies a
controlled burn to a portion of the prairie to attract cattle, creating a mosaic
of more- and less-grazed patches. Although beneficial to cattle and grassland
birds, the potential impacts of PBG on streams have not been studied, and a
holistic approach is needed to ensure against adverse effects. We used a Before
After-Control-Impact design to assess potential impacts of PBG with and without
riparian protection on tallgrass prairie headwater streams. We sampled stream
macroinvertebrates and benthic organic matter 2 yr before and 2 yr during PBG
treatments on two grazed watersheds with riparian fencing (fenced), two unfenced
grazed watersheds (unfenced), and two ungrazed (control) watersheds. Very fine
benthic organic matter increased significantly (51%) in unfenced streams compared
with controls ( < 0.007), and fine particulate organic matter (<1 mm and >250 um)
increased 3-fold in the unfenced streams compared with controls ( = 0.008). The
contribution of fine inorganic sediments to total substrata increased 28% in
unfenced streams during PBG, which was significantly different from controls ( =
0.03). Additionally, the abundance of Ephemeroptera, Plecoptera, and Trichoptera
taxa decreased from 7635 to 687 individuals m in unfenced streams, which was
significantly lower than in control streams ( = 0.008). Our results indicate that
PBG adversely influences prairie streams through sediment inputs and reductions
in sensitive invertebrate taxa, but riparian fencing can alleviate these impacts.
PMID- 26437097
TI - The Effect of the Moisture Regime on the Interaction of Fluorene with Porous
Media.
AB - Movement and persistence of organic molecules in porous media is strongly
influenced by their interactions with the solid phase. Understanding these
interactions is important for the execution of reliable risk assessments and for
proper handling and disposal of toxic organic chemicals. Transport and
attenuation models often assume rapid adsorption-desorption equilibration and
neglect the role of the ever-changing moisture regime at the top of the vadose
zone. Adsorption of the polyaromatic hydrocarbon fluorene (CH), both from hexane
and from water, on a cattle manure compost and on two soils-Dor
(montmorillonitic, 1.9% organic matter [OM]) and Maagan-Michael (kaolinitic, 5.2%
OM)-was studied. Adsorption from hexane mimics interactions with surfaces exposed
to a gas phase or to an apolar liquid. Desorption was measured after loading the
sorbents with fluorene dissolved in hexane, evaporating the solvent, and
incubation in the wet state (above saturation of the porous medium), air-dried,
or while undergoing wetting-drying cycles. Although good correlation was observed
between the adsorption coefficient of fluorene from water and OM content,
adsorption from hexane highly correlated with the surface charge density of the
sorbent (its cation exchange capacity or its polarity). When added to the
sorbents from hexane and then desorbed into water, less fluorene desorbed than
predicted by its aqueous adsorption isotherms. Desorption from all sorbents
decreased as the duration of incubation at air dryness increased. Thus, fluorene
exhibited adsorption-desorption hysteresis, and a particularly strong adsorption
desorption hysteresis was exhibited by fluorene-loaded Maagan-Michael soil after
undergoing wetting-drying cycles.
PMID- 26437098
TI - The Role of Hydrology in the Polychlorinated Dibenzo--dioxin and Dibenzofuran
Distributions in a Lowland River.
AB - Persistent organic pollutants such as polychlorinated dibenzo--dioxins (PCDDs)
and polychlorinated dibenzofurans (PCDFs) are environmental contaminants that
have widespread distribution and pose a serious threat to aquatic ecosystems. We
conducted a study to quantify the distribution, patterns, and transport of PCDDs
and PCDFs along the Pilica River in central Poland under different hydrological
conditions to estimate the loads of these compounds and understand their fate in
aquatic systems. Water samples were collected at five sampling points along the
river that represent a range of hydrological conditions including flooding and
stable and low water flows. Reduced river water flow was associated with lower
average total and toxic equivalent (TEQ) concentrations of PCDDs plus PCDFs: 33.6
pg L and 4.21 pg TEQ L for flooding; 28.3 pg L and 3.6 pg TEQ L for stable flow;
18.4 pg L and 1.0 pg TEQ L for low-water flow. Similar results were observed for
daily loadings of total and TEQ concentrations: the highest values were observed
during flooding (331.1-839.4 mg d and 27.8-110.7 mg TEQ d), medium under stable
hydrological conditions (55.8-121.0 mg d and 7.7-15.3 mg TEQ d), and the lowest
values during low water flow (30.9 and 40.3 mg d and 1.4-2.4 mg TEQ d). The
results demonstrate that diffuse sources of pollution play a key role during
periods of high water flow (i.e., flooding season), whereas point sources of
pollution, including municipal and industrial wastewater treatment plant
discharges, mainly determine the PCDD and PCDF concentrations seen during low
water periods.
PMID- 26437099
TI - Adsorption of Sulfamethazine from Environmentally Relevant Aqueous Matrices onto
Hypercrosslinked Adsorbent MN250.
AB - Four hundred tons of sulfamethazine are fed to livestock annually in North
America for disease prevention and growth promotion, but the majority is excreted
unmetabolized into the environment. Due to its slow degradation and high
mobility, sulfamethazine contaminates groundwater and causes aquatic ecosystem
damage. Sulfamethazine remediation methods are not universally effective,
necessitating newer techniques. Hypercrosslinked polystyrene adsorbents show
promise because of high surface areas, durability, and regenerable properties.
Using batch techniques, sulfamethazine adsorption onto Purolite MN250 was
evaluated in the presence of dissolved humic acid and under variable pH and ionic
strength. The adsorption capacity () of MN250 for sulfamethazine with humic acid
was 109.3 mg g. In simulated groundwater, at pH 5 was 51 to 62% higher than at pH
9. The maximum at pH 7 (144.0 mg g) exceeded pH 5 performance (128.3 mg g). In
0.005 M KCl, was 181.0 mg g, which decreased by 34% in 0.05 M KCl. In 0.5 M, KCl,
(153.4 mg g) increased 26% over 0.05 M KCl. For all matrices, equilibration was
attained between 120 and 168 h, best fit by Ho's pseudo-second-order model.
Overall, is pH dependent because the sulfamethazine speciation and the zeta
potential of MN250 vary as a function of pH. Increasing ionic strength initially
decreases by altering the activity coefficient of sulfamethazine and by altering
the properties of the electrical double layer, while salting-out becomes
prominent at seawater concentration. MN250's high sulfamethazine capacity in
environmentally relevant aqueous matrices highlights its potential for
groundwater remediation.
PMID- 26437100
TI - Occurrence and Fate of Trace Contaminants during Aerobic and Anaerobic Sludge
Digestion and Dewatering.
AB - Digestion of municipal wastewater biosolids is a necessary prerequisite to their
beneficial use in land application, in order to protect public health and the
receiving environment. In this study, 13 pharmaceuticals and personal care
products (PPCPs), 11 musks, and 17 polybrominated diphenyl ethers were analyzed
in 84 samples including primary sludge, waste activated sludge, digested
biosolids, dewatered biosolids, and dewatering centrate or filtrate collected
from five wastewater treatment plants with aerobic or anaerobic digestion.
Aerobic digestion processes were sampled during both warm and cold temperatures
to analyze seasonal differences. Among the studied compounds, triclosan,
triclocarban, galaxolide, and BDE-209 were the substances most frequently
detected under different treatment processes at levels up to 30,000 ng/g dry
weight. Comparing aerobic and anaerobic digestion, it was observed that the
levels of certain PPCPs and musks were significantly higher in anaerobically
digested biosolids, relative to the residues from aerobic digestion. Therefore,
aerobic digestion has the potential advantage of reducing levels of PPCPs and
musks. On the other hand, anaerobic digestion has the advantage of recovering
energy from the biosolids in the form of combustible gases while retaining the
nutrient and soil conditioning value of this resource.
PMID- 26437101
TI - Phytoextraction of DDT-Contaminated Soil at Point Pelee National Park,
Leamington, ON, Using Cultivar Howden and Native Grass Species.
AB - A field investigation was conducted at three dichlorodiphenyltrichloroethane
(DDT)-contaminated areas in Point Pelee National Park (PPNP), Leamington, ON.
cultivar Howden and three native grass species, (Michx.) Nash (little bluestem),
L. (switchgrass), and (Torr.) A. Gray (sand dropseed) were grown at three
different sites in the PPNP having low (291 ng/g), moderate (5083 ng/g), and high
(10,192 ng/g) soil DDT contamination levels. A threshold soil DDT concentration
was identified at ~5000 ng/g where the DDT uptake into was maximized, resulting
in plant shoot and root DDT concentrations of 16,600 and 45,000 ng/g,
respectively. Two native grass species ( and ) were identified as potential
phytoextractors, with higher shoot extraction capabilities than that of the known
phytoextractor when optimal planting density was taken into account.
PMID- 26437102
TI - Can Coarse Woody Debris Be Used for Carbon Storage in Open Grazed Woodlands?
AB - Carbon dioxide off-setting policy in the agricultural sector is focused on
manipulating the terrestrial carbon cycle by reafforestation and increasing the
retention of carbon within agricultural soils. We quantified the amount of carbon
stored in the living and dead biomass and the surface soils of a previously
grazed woodland ecosystem. We demonstrate that modification of coarse woody
debris management could potentially store 8 to 15 t C ha. This large carbon pool
raises the prospect that appropriate management of temperate woodlands to retain
coarse woody debris and increase its volume into the future could achieve
increased landscape carbon storage.
PMID- 26437103
TI - Dissolved Phosphorus Retention in Buffer Strips: Influence of Slope and Soil
Type.
AB - Phosphorus (P) contributes to eutrophication of surface waters and buffer strips
may be implemented to reduce its transfer from agricultural sources to
watercourses. This study was conducted to test the hypothesis that soil type and
slope influence the retention of dissolved organic P and inorganic orthophosphate
in agricultural runoff in 2-m-wide buffer strip soils. A solution, comprised of
dissolved orthophosphate and the organic P compounds glucose-1-phosphate, RNA,
and inositol hexakisphosphate (1.8 mg L total P) and a chloride tracer, was
applied as simulated overland flow to grassland soil blocks (2 m long * 0.5 m
wide * 0.35 m deep), containing intact clay or loam soils, at slope angles of 2,
5, and 10 degrees . Phosphorus forms were determined in the surface and
subsurface flow from the soil blocks. Slope had no significant effect on the
hydrological behavior of the soil blocks or on the retention of any form of P at
the water application rate tested. The clay soil retained 60% of the unreactive P
and 21% of the reactive P applied. The loam soil retained 74% of the unreactive P
applied but was a net source of reactive P (the load increased by 61%). This
indicates leaching of native soil P or hydrolysis of organic compounds and
complicates our understanding of P retention in buffer strip soils. Our results
suggest that a 2-m buffer strip may be more effective for reducing dissolved
unreactive P transfers to surface waters than for reducing the eutrophication
risk posed by dissolved reactive P.
PMID- 26437104
TI - A Nitrogen-Saturated Plantation of and in Japan Is a Large Nonpoint Nitrogen
Source.
AB - Japanese cedar () and Japanese cypress () plantations account for approximately
30% of the total forested area in Japan. Both are arbuscular mycorrhizal trees
that leach more NO in response to nitrogen (N) deposition than do forests of
ectomycorrhizal trees. However, little information is available about the size of
N exports from these plantations. The aim of this study was to evaluate nonpoint
source N exports from a N-saturated plantation. We collected stream water samples
in base-flow (25 samples) and storm-flow conditions (20 events) in a watershed
(2.98 ha) where Japanese cypress and Japanese cedar were planted in 1969 (41 yr
old). The annual NO export was calculated from load-discharge relationships.
Atmospheric N deposition was also determined. The stream water contained high NO
concentrations (160 and 165 MUmol L during base flow and storm flow,
respectively), indicating N saturation in the watershed. High bulk atmospheric N
deposition (16.5 kg N ha yr) could explain the N saturation. There were only
small variations in NO concentrations in stream water in response to discharge
volume, because of the N saturation of the forest ecosystem. Consequently, there
were only small errors in estimating annual NO exports from the studied
watershed. The annual NO export was high (36.1 kg N ha yr), comparable to values
reported for agricultural and urbanized areas. These results suggest that N
saturated forest plantations can become important nonpoint N sources. Our results
also suggest that N exports from forest plantations across Japan should be
quantified to evaluate nonpoint source N accurately.
PMID- 26437105
TI - Monitoring Fipronil and Degradates in California Surface Waters, 2008-2013.
AB - The phenylpyrazole insecticide fipronil has become a popular replacement pest
management tool as organophosphorus insecticides have been phased out for
residential use and pyrethroids have come under scrutiny as a surface water
contaminant. There has been an increasing concern of offsite transport of
fipronil to surrounding surface waters and a corresponding increase in potential
toxicity to aquatic organisms. The California Department of Pesticide Regulation
Environmental Monitoring Program has collected over 500 urban surface water
samples throughout California since 2008 to determine the presence and
concentrations of fipronil and five degradate products. Statewide, fipronil was
detected at high frequency (49%), as were the sulfone (43%) and desulfinyl (33%)
degradates. Data collected at long-term monitoring stations indicate higher
concentrations in southern California, corresponding to a higher use pattern in
the region. There is a clear pattern of increased transport of fipronil with
higher flow associated with rain events. However, the lack of seasonality effects
on degradates' concentrations suggest a constant source of fipronil with a
corresponding lag time of transport to surface waters during the dry season.
Receiving waters had a diluting effect on concentrations; however, a significant
proportion (46%) of receiving water samples had associated fipronil
concentrations above USEPA aquatic life chronic benchmark values. Total mass
loading estimates from a long-term monitoring site suggest that the annual
fipronil loading is greater in the dry season than during storm events. This
could have implications for future mitigation efforts because most runoff during
this period was generated from irrigation and outdoor residential use.
PMID- 26437106
TI - Heavy Rainfall Impacts on Trihalomethane Formation in Contrasting Northwestern
European Potable Waters.
AB - There is emerging concern over the impact of extreme events such as heavy
rainfall on the quality of water entering the drinking water supply from
aboveground sources, as such events are expected to increase in magnitude and
frequency in response to climate change. We compared the impact of rainfall
events on streamwater quality in four contrasting upland (peatland and mineral
soil) and lowland agricultural catchments used to supply drinking water in France
(Brittany) and the United Kingdom (North Wales) by analyzing water samples
collected before, during, and after specific events. At all four streams, heavy
rainfall led to a considerable rise in organic matter concentration ranging from
48 to 158%. Dissolved organic carbon (DOC) quality, as determined using specific
ultraviolet absorbance, changed consistently at all sites during rainfall events,
with a greater proportion of aromatic and higher molecular weight compounds
following the onset of rainfall. However, the change in DOC quality and quantity
did not significantly alter the trihalomethane formation potential. We observed
small increases in trihalomethane (THM) generation only at the Welsh peatland and
agricultural sites and a small decrease at the Brittany agricultural site. The
proportion of brominated THMs in chlorinated waters was positively correlated
with bromide/DOC ratio in raw waters for all sites and hydrological conditions.
These results provide a first indication of the potential implications for
surface-based drinking water resources resulting from expected future increases
in rainfall event intensity and extension of dry periods with climate changes.
PMID- 26437107
TI - Phosphorus Mobilization from Manure-Amended and Unamended Alkaline Soils to
Overlying Water during Simulated Flooding.
AB - Anaerobic soil conditions resulting from flooding often enhance release of
phosphorus (P) to overlying water. Enhanced P release is well documented for
flooded acidic soils; however, there is little information for flooded alkaline
soils. We examined the effect of flooding and anaerobic conditions on P
mobilization using 12 alkaline soils from Manitoba that were either unamended or
amended with solid cattle manure. Pore water and floodwater were analyzed over 8
wk of simulated flooding for dissolved reactive P (DRP), Ca, Mg, Fe, and Mn. As
expected, manured soils had significantly greater pore and floodwater DRP
concentrations than unamended. Flooding increased pore water DRP concentrations
significantly in all soils and treatments except one manured clay in which
concentrations increased initially and then decreased. Floodwater DRP
concentrations increased significantly by two- to 15-fold in 10 soils regardless
of amendment treatment but remained relatively stable in the two soils with
greatest clay content. Phosphorus release at the onset of flooding was associated
with the release of Ca, Mg, and Mn, suggesting that P release may be controlled
by the dissolution of Mg and Ca phosphates and reductive dissolution of Mn
phosphates. Thereafter, P release was associated with release of Fe, suggesting
the reductive dissolution of Fe phosphates. Differences in pore water and
floodwater DRP concentrations among soils and amendment treatments and the high
variability in P mobilization from pore water to floodwater among soils indicate
the need to further investigate chemical reactions responsible for P release and
mobility under anaerobic conditions.
PMID- 26437108
TI - Effects of Site Preparation for Pine Forest/Switchgrass Intercropping on Water
Quality.
AB - A study was initiated to investigate the sustainability effects of intercropping
switchgrass ( L.) in a loblolly pine ( L.) plantation. This forest-based biofuel
system could possibly provide biomass from the perennial energy grass while
maintaining the economics and environmental benefits of a forest managed for
sawtimber. Operations necessary for successful switchgrass establishment and
growth, such as site preparation, planting, fertilizing, mowing and baling, may
affect hydrology and nutrient runoff. The objectives of this study were (i) to
characterize the temporal effects of management on nutrient concentrations and
loadings and (ii) to use pretreatment data to predict those treatment effects.
The study watersheds (~25 ha each) in the North Carolina Atlantic Coastal Plain
were a pine/switchgrass intercropped site (D1), a midrotation thinned pine site
with natural understory (D2), and a switchgrass-only site (D3). Rainfall,
drainage, water table elevation, nitrogen (total Kjedahl N, NH-N, and NO-N), and
phosphate were monitored for the 2007-2008 pretreatment and the 2009-2012
treatment periods. From 2010 to 2011 in site D1, the average NO-N concentration
effects decreased from 0.18 to -0.09 mg L, and loads effects decreased from 0.86
to 0.49 kg ha. During the same period in site D3, the average NO-N concentration
effects increased from 0.03 to 0.09 mg L, and loads effects increased from -0.26
to 1.24 kg ha. This study shows the importance of considering water quality
effects associated with intensive management operations required for switchgrass
establishment or other novel forest-based biofuel systems.
PMID- 26437109
TI - Effect of Biochar on Nutrient Leaching in a Young Apple Orchard.
AB - Nutrient leaching from agricultural soils is a worldwide problem that has been
implicated in deleterious impacts on the environment. Application of biochar to
soil has been proposed as a means to reduce nutrient leaching and improve
fertilizer use efficiency. The potential for biochar to reduce nutrient leaching
and increase fertilizer use efficiency was tested by applying 47 Mg ha hardwood
biochar before replanting a commercial apple () orchard, in the Huon Valley,
Tasmania. Passive wick flux meters were installed at the base of the A1 horizon
at a depth of 25 cm to monitor leachate volume and the concentration of nutrients
leached below the A1 soil horizon over a 38 mo period. Biochar application
significantly increased the concentration of phosphorous in the leachate, while
having no significant effect on nitrate or potassium concentration. The volume of
leachate collected in the flux meters was significantly higher in the biochar
treatment, which resulted in significantly higher amounts of potassium and
phosphorous being leaching from the biochar treatment than the control. Biochar
application had no significant effect on either the concentration or the flux of
nitrate leached from the A1 horizon. Nonetheless, nutrient application was well
in excess of tree requirements, such that between 53 to 78% of the applied
nitrogen, 5 to 11% of the applied phosphate, and 69 to 112% of the applied
potassium were leached below the A1 horizon.
PMID- 26437110
TI - Titration and Spectroscopic Measurements of Poultry Litter pH Buffering Capacity.
AB - The pH value of poultry litter is affected by nitrification, mineralization, and
the addition of acidifying chemicals, all acting on the poultry litter pH
buffering capacity (pHBC). Increased understanding of poultry litter pHBC will
aid in modeling NH volatilization from surface-applied poultry litter as well as
estimating rates of alum applications. Our objectives were to (i) determine the
pHBC of a wide range of poultry litters; (ii) assess the accuracy of near
infrared reflectance spectroscopy (NIRS) for determining poultry litter pHBC; and
(iii) demonstrate the use of poultry litter pHBC to increase the accuracy of alum
additions. Litter pHBC was determined by titration and calculated from linear and
sigmoidal curves. For the 37 litters measured, linear pHBC ranged from 187 to 537
mmol (pH unit) kg dry litter. The linear and sigmoidal curves provided accurate
predictions of pHBC, with most > 0.90. Results from NIRS analysis showed that the
linear pHBC expressed on an "as is" water content basis had a NIRS coefficient of
calibration (developed using a modified partial least squares procedure) of 0.90
for the 37 poultry litters measured. Using the litter pHBC, an empirical model
was derived to determine the amount of alum needed to create a target pH. The
model performed well in the range of pH 6.5 to 7.5 (RMSE = 0.07) but
underpredicted the amount of alum needed to reach pH <6. The lack of model
performance at pH <6 was probably due to Al reacting with organic matter in the
poultry litter, which prevented its hydrolysis.
PMID- 26437111
TI - Nitrogen and Phosphorus Loss Potential from Biosolids-Amended Soils and Biotic
Response in the Receiving Water.
AB - Application of municipal biosolids to agricultural soil can improve soil quality
and improve crop yields. However, runoff or tile leachate from biosolids-applied
fields may contribute to localized eutrophication of surface water. A laboratory
experiment was conducted to determine loss potential of nutrients from soils
amended with two different biosolids (anaerobically digested and chemically
stabilized) relative to loss from a reference soil and to determine response in
freshwater microcosms to nutrients lost from soils. Total phosphorus (TP) and
total nitrogen (TN) were measured in runoff, and equivalent amounts were added to
reference microcosms to determine if aquatic systems would respond similarly to
TN and TP loading in bioavailable forms (PO, NH, NO) simulating loading related
to inorganic fertilizer application. Nutrient concentrations (TP, TN, PO, NH, NO,
and organic P and N) were similar in the runoff from the two biosolids-amended
soils and higher than those in the runoff from the reference soil. Runoff from
biosolids-amended soils stimulated algal growth and production (chlorophyll a and
dissolved oxygen) relative to runoff from reference soil, but the response was
weaker than in microcosms receiving equivalent amounts of inorganic N and P.
Nutrient runoff from land-applied biosolids does have potential to increase algal
production in receiving waters; however, this experiment suggests receiving
waters may absorb a single large nutrient loading event associated with runoff
from biosolids-amended soil without substantial impact. Moreover, the response to
N and P in biosolids versus inorganic nutrient additions suggests biosolids may
contribute relatively less to eutrophication than inorganic fertilizers, assuming
equivalent TN and TP loading to aquatic systems.
PMID- 26437112
TI - Contrasting Nutrient Mitigation and Denitrification Potential of Agricultural
Drainage Environments with Different Emergent Aquatic Macrophytes.
AB - Remediation of excess nitrogen (N) in agricultural runoff can be enhanced by
establishing wetland vegetation, but the role of denitrification in N removal is
not well understood in drainage ditches. We quantified differences in N retention
during experimental runoff events followed by stagnant periods in mesocosms
planted in three different vegetation treatments: unvegetated, cutgrass [ (L.)
Sw.], and common cattail ( L.). We also quantified denitrification rates using
membrane inlet mass spectrometry from intact cores extracted from each mesocosm
treatment. All treatments retained 60% or more of NO-N loads during the 6-h
experimental runoff event, but mesocosms planted with cutgrass had significantly
higher (68%) retention than the cattail (60%) or unvegetated (61%) treatments.
After the runoff event, mesocosms planted in cattail reduced NO-N concentrations
by >95% within 24 h and cutgrass achieved similar reductions within 48 h, whereas
reductions in the unvegetated mesocosms were significantly less (65%). Cores from
cutgrass mesocosms had significantly higher average denitrification rates (5.93
mg m h), accounting for as much as 56% of the immobilized NO-N within 48 h,
whereas denitrification rates were minimal in cores from the unvegetated (-0.19
mg m h) and cattail (0.2 mg m h) mesocosms. Our findings have implications for
mitigating excess NO-N in agricultural runoff. While vegetated treatments removed
excess NO-N from the water column at similar and significantly higher rates than
unvegetated treatments, the high denitrification rates observed for cutgrass
highlight the potential for permanent removal of excess N from agricultural
runoff in vegetated ditches and wetlands.
PMID- 26437113
TI - Biochar Soil Amendment Effects on Arsenic Availability to Mountain Brome ().
AB - Biochar is a renewable energy byproduct that shows promise for remediating
contaminated mine sites. A common contaminant at mine sites is arsenic (As). In
this study, the effects of biochar amendments to a mine-contaminated soil on As
concentrations in mountain brome ( Nees ex Steud.) were investigated. In the
biochar-amended soil, mountain brome had greater root biomass and decreased root
and shoot As concentrations. X-ray absorption near-edge structure spectroscopy
results showed that arsenate [As(V)] is the predominant species in both the
nonamended and biochar-amended soils. Soil extraction tests that measure
phosphate and arsenate availability to plants failed to accurately predict plant
tissue As concentrations, suggesting the arsenate bioavailability behavior in the
soils is distinct from phosphate. Results from this study indicate that biochar
will be a beneficial amendment to As-contaminated mine sites for remediation.
PMID- 26437114
TI - Chemical Fouling Reduction of a Submersible Steel Spectrophotometer in Estuarine
Environments Using a Sacrificial Zinc Anode.
AB - The availability of in situ spectrophotometers, such as the S::CAN
spectro::lyser, has expanded the possibilities for high-frequency water quality
data collection. However, biological and chemical fouling can degrade the
performance of in situ spectrophotometers, especially in saline environments with
rapid flow rates. A complex freshwater washing system has been previously
designed to reduce chemical fouling for the S::CAN spectro::lyser
spectrophotometer. In the current study, we present a simpler, cheaper
alternative: the attachment of a sacrificial zinc anode. Results are presented
detailing the S::CAN spectro::lyser performance with and without the addition of
the sacrificial anode. Attachment of the zinc anode provided efficient corrosion
protection during 2-wk deployments in a highly dynamic (average tidal range, 2.5
m) saline tidal saltmarsh creek at Groves Creek, Skidaway Institute of
Oceanography, Savannah, GA.
PMID- 26437115
TI - Chemical and Isotopic Tracers Illustrate Pathways of Nitrogen Loss in Cranberry
Floodwaters.
AB - Limited research exists on the sources of nitrogen (N) in cranberry floodwaters,
which have been identified as a prominent cause of concern to watershed N loading
in the cranberry-producing region of southeastern Massachusetts. In this study,
we used naturally occurring chemical and isotopic tracers to infer the sources of
N transported by harvest floodwaters. In 2012, the cranberry bed was a net source
of total N (TN), exporting 0.8 kg N ha (primarily as organic N) to a nearby lake.
Systematic increases in TN concentration were associated with increasing
fractions of pre-event soil water and groundwater ("porewater") in discharge.
Results showed that N concentrations in porewater generally derive from the
natural mixing of soil water and perched groundwater within the cranberry bed but
locally display a connection to deep groundwater where the underlying peat is
absent. These findings illustrate the environmental significance of stored pools
of porewater in cranberry beds and the ability to focus on moments of
disproportionate N transfer to most efficiently curtail floodwater N losses
(i.e., 58% of N export occurred in only 22% of floodwater discharge).
PMID- 26437116
TI - Prognostic biomarkers for renal amyloid.
PMID- 26437118
TI - Two-Color Single Hybrid Plasmonic Nanoemitters with Real Time Switchable Dominant
Emission Wavelength.
AB - We demonstrate two-color nanoemitters that enable the selection of the dominant
emitting wavelength by varying the polarization of excitation light. The
nanoemitters were fabricated via surface plasmon-triggered two-photon
polymerization. By using two polymerizable solutions with different quantum dots,
emitters of different colors can be positioned selectively in different
orientations in the close vicinity of the metal nanoparticles. The dominant
emission wavelength of the metal/polymer anisotropic hybrid nanoemitter thus can
be selected by altering the incident polarization.
PMID- 26437119
TI - The relationship between adolescents' physical activity, fundamental movement
skills and weight status.
AB - The aim of this study was to determine if a potential relationship among physical
activity (PA), fundamental movement skills and weight status exists amongst early
adolescent youth. Participants were a sample of 85 students; 54 boys (mean age =
12.94 +/- 0.33 years) and 31 girls (mean age = 12.75 +/- 0.43 years). Data
gathered during physical education class included PA (accelerometry), fundamental
movement skills and anthropometric measurements. Standard multiple regression
revealed that PA and total fundamental movement skill proficiency scores
explained 16.5% (P < 0.001) of the variance in the prediction of body mass index.
Chi-square tests for independence further indicated that compared with overweight
or obese adolescents, a significantly higher proportion of adolescents classified
as normal weight achieved mastery/near-mastery in fundamental movement skills.
Results from the current investigation indicate that weight status is an
important correlate of fundamental movement skill proficiency during adolescence.
Aligned with most recent research, school- and community-based programmes that
include developmentally structured learning experiences delivered by specialists
can significantly improve fundamental movement skill proficiency in youth.
PMID- 26437120
TI - Modeling the Effects of Hydrodynamic Regimes on Microbial Communities within
Fluvial Biofilms: Combining Deterministic and Stochastic Processes.
AB - To fully understand the effects of hydrodynamics on a microbial community, the
roles of niche-based and neutral processes must be considered in a mathematical
model. To this end, a two-dimensional model combining mechanisms of immigration,
dispersal, and niche differentiation was first established to describe the
effects of hydrodynamics on bacterial communities within fluvial biofilms.
Deterministic factors of the model were identified via the calculation of
Spearman's rank correlation coefficients between parameters of hydrodynamics and
the bacterial community. It was found that turbulent kinetic energy and turbulent
intensity were considered as a set of reasonable predictors of community
composition, whereas flow velocity and turbulent intensity can be combined
together to predict biofilm bacterial biomass. According to the modeling result,
the bacterial community could get its favorable assembly condition with a flow
velocity ranging from 0.041 to 0.061 m/s. However, the driving force for biofilm
community assembly changed with the local hydrodynamics. Individuals reproduction
within the biofilm was the main driving force with flow velocity less than 0.05
m/s, while cell migration played a much more important role with velocity larger
than 0.05 m/s. The developed model could be considered as a useful tool for
improving the technologies of water environment protection and remediation.
PMID- 26437117
TI - Synaptotagmin-1 and -7 Are Redundantly Essential for Maintaining the Capacity of
the Readily-Releasable Pool of Synaptic Vesicles.
AB - In forebrain neurons, Ca(2+) triggers exocytosis of readily releasable vesicles
by binding to synaptotagmin-1 and -7, thereby inducing fast and slow vesicle
exocytosis, respectively. Loss-of-function of synaptotagmin-1 or -7 selectively
impairs the fast and slow phase of release, respectively, but does not change the
size of the readily-releasable pool (RRP) of vesicles as measured by stimulation
of release with hypertonic sucrose, or alter the rate of vesicle priming into the
RRP. Here we show, however, that simultaneous loss-of-function of both
synaptotagmin-1 and -7 dramatically decreased the capacity of the RRP, again
without altering the rate of vesicle priming into the RRP. Either synaptotagmin-1
or -7 was sufficient to rescue the RRP size in neurons lacking both synaptotagmin
1 and -7. Although maintenance of RRP size was Ca(2+)-independent, mutations in
Ca(2+)-binding sequences of synaptotagmin-1 or synaptotagmin-7--which are
contained in flexible top-loop sequences of their C2 domains--blocked the ability
of these synaptotagmins to maintain the RRP size. Both synaptotagmins bound to
SNARE complexes; SNARE complex binding was reduced by the top-loop mutations that
impaired RRP maintenance. Thus, synaptotagmin-1 and -7 perform redundant
functions in maintaining the capacity of the RRP in addition to nonredundant
functions in the Ca(2+) triggering of different phases of release.
PMID- 26437121
TI - Associated extrarenal vascular diseases may complicate the treatment and outcome
of renovascular hypertension.
AB - AIM: This studied reviewed renovascular hypertension (RVH) due to renal artery
stenosis (RAS) in two Serbian paediatric centres from 2001 to 2013. METHODS: The
patients' demographic data, underlying syndromes, blood pressure (BP),
antihypertensive treatments and outcomes were reviewed. RESULTS: The incidence of
RVH was 1.9 per million children per year during the study period, and there were
25 patients with RAS, aged 10.4 +/- 5.2 years. At presentation, their mean blood
pressure (BP) standard deviation scores were 6.9 +/- 3.4 systolic and 5.2 +/- 2.6
diastolic. BP loads on 24-hour ambulatory BP were 88 +/- 14% systolic and 80 +/-
29% diastolic. We found that 72% had fibromuscular dysplasia and 28% had
underlying syndromes. RAS was unilateral in 64% and bilateral in 28%, and 8% had
RAS of a single kidney. Antihypertensive treatment included antihypertensive
drugs (100%), percutaneous transluminal angioplasty (92%), renal auto
transplantation (16%), surgical revascularisation (12%) and nephrectomy (12%).
After 4.4 +/- 3.6 years of follow-up, high BP was cured in 40% of the patients
and 39.4% of the kidneys and improved in 48% (75.7%), with BP decreases of 20.3
+/- 3.7% systolic and 16.3 +/- 6.2% diastolic. CONCLUSION: Fibromuscular
dysplasia was the most common cause of RVH in this study, and hypertension was
cured or improved in 88% of the patients.
PMID- 26437122
TI - Liver fluke-infested graft used for living-donor liver transplantation: case
report and review of the literature.
AB - Clonorchiasis is a cholangiopathy caused by foodborne trematode parasites, also
known as liver flukes. Clonorchiasis is endemic in a wide geographical area
extending from Eastern Europe to Southeast Asia. Infested hosts may remain
asymptomatic for decades and consequently their liver can become available as a
graft. To date, 20 liver transplantations with liver fluke-infested grafts have
been reported in the literature. All of them occurred in Asian countries. We,
here, report the first case to our knowledge in the Western world of living-donor
liver transplantation (LDLT) with an Opisthorchis felineus-infested graft, and
present a review of the literature. A 6-month-old girl with decompensated
secondary biliary cirrhosis underwent an LDLT with a left lateral graft infested
with O. felineus. After prompt diagnosis and adequate therapy, both donor and
recipient had an uneventful postoperative course and long-term follow-up. Liver
grafts infested with liver flukes do not pose a contraindication to liver
donation from deceased or living donors, provided that a correct diagnosis and
treatment are performed in a timely fashion.
PMID- 26437123
TI - Role of beta-Amyloidosis and Neurodegeneration in Subsequent Imaging Changes in
Mild Cognitive Impairment.
AB - IMPORTANCE: To understand how a model of Alzheimer disease pathophysiology based
on beta-amyloidosis and neurodegeneration predicts the regional anatomic
expansion of hypometabolism and atrophy in persons with mild cognitive impairment
(MCI). OBJECTIVE: To define the role of beta-amyloidosis and neurodegeneration in
the subsequent progression of topographic cortical structural and metabolic
changes in MCI. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, observational
study with serial brain imaging conducted from March 28, 2006, to January 6,
2015, using a population-based cohort. A total of 96 participants with MCI (all
aged >70 years) with serial imaging biomarkers from the Mayo Clinic Study of
Aging or Mayo Alzheimer's Disease Research Center were included. Participants
were characterized initially as having elevated or not elevated brain beta
amyloidosis (A+ or A-) based on 11C-Pittsburgh compound B positron emission
tomography. They were further characterized initially by the presence or absence
of neurodegeneration (N+ or N-), where the presence of neurodegeneration was
defined by abnormally low hippocampal volume or hypometabolism in an Alzheimer
disease-like pattern on 18fluorodeoxyglucose (FDG)-positron emission tomography.
MAIN OUTCOMES AND MEASURES: Regional FDG standardized uptake value ratio (SUVR)
and gray matter volumes in medial temporal, lateral temporal, lateral parietal,
and medial parietal regions. RESULTS: In the primary regions of interest (ROI),
the A+N+ group (n = 45) had lower FDG SUVR at baseline compared with the A+N-
group (n = 17) (all 4 ROIs; P < .001). The A+N+ group also had lower FDG SUVR at
baseline (all 4 ROIs; P < .01) compared with the A-N- group (n = 12). The A+N+
group had lower medial temporal gray matter volume at baseline (P < .001)
compared with either the A+N- group or A-N- group. The A+N+ group showed large
longitudinal declines in FDG SUVR (P < .05 for medial temporal, lateral temporal,
and medial parietal regions) and gray matter volumes (P < .05 for medial temporal
and lateral temporal regions) compared with the A-N+ group (n = 22). The A+N+
group also showed large longitudinal declines compared with the A-N- group on FDG
SUVR (P < .05 for medial temporal and lateral parietal regions) and gray matter
volumes (all 4 ROIs; P < .05) compared with the A+N- group. The A-N+ group did
not show declines in FDG SUVR or gray matter volume compared with the A+N- or A-N
groups. CONCLUSIONS AND RELEVANCE: Persons with MCI who were A+N+ demonstrated
volumetric and metabolic worsening in temporal and parietal association areas,
consistent with the expectation that the MCI stage in the Alzheimer pathway
heralds incipient isocortical involvement. The A-N+ group, those with suspected
non-Alzheimer pathophysiology, lacked a distinctive longitudinal volumetric or
metabolic profile.
PMID- 26437124
TI - Complete mitochondrial genome of Bombus terrestris (Hymenoptera: Apidae).
AB - In this study, complete mitochondrial genome of the large earth bumblebee, Bombus
terrestris, was first determined. The mitochondrial genome is 174 000 bp in
length, and encodes 1 D-loop region, 2 ribosomal RNA genes, 13 protein-coding
genes and 20 transfer RNA genes. Average GC content of this genome is 15%. nad6
and cob are overlapped with 12 bp, while atp8 and atp6 are overlapped with 18 bp.
Phylogeny analysis indicates Bombus species exhibit closer genetic distance with
Melipona species than with Apis species.
PMID- 26437125
TI - Amphibian molecular ecology and how it has informed conservation.
AB - Molecular ecology has become one of the key tools in the modern conservationist's
kit. Here we review three areas where molecular ecology has been applied to
amphibian conservation: genes on landscapes, within-population processes, and
genes that matter. We summarize relevant analytical methods, recent important
studies from the amphibian literature, and conservation implications for each
section. Finally, we include five in-depth examples of how molecular ecology has
been successfully applied to specific amphibian systems.
PMID- 26437126
TI - Effects of vagus nerve stimulation on pupillary function.
AB - BACKGROUND: Chronic vagus nerve stimulation (VNS) is a recognized treatment for
refractory epilepsy and depression. The vagus nerve projects to several brainstem
autonomic structures. As pupillary measures are an easy and non-invasive method
to evaluate autonomic functioning, we used resting diameter and light reflex
measures to investigate the influence of VNS on the human central autonomic
nervous system. METHOD: We studied 21 patients (7 with major depression, 14 with
epilepsy) treated with chronic VNS (30s ON, 5 min OFF stimulation trains).
Resting pupil size and light reflex measures were compared in consecutive
intervals with (ON) and without stimulation (OFF). RESULTS: Compared to the OFF
condition, the ON condition was associated with a significant increase in resting
pupil diameter, but did not affect light reflex measures. There was no group
difference between the two populations of patients (depression and epilepsy) on
any of the pupil measures. CONCLUSION: VNS at clinically significant levels
increases resting pupil diameter.
PMID- 26437127
TI - Reduced Leaflet Motion in Bioprosthetic Aortic Valves--The FDA Perspective.
PMID- 26437128
TI - Statins and their increased risk of inducing diabetes.
AB - INTRODUCTION: Statins are evidence-based drugs to prevent cardiovascular (CV)
disease. However, their benefits have been disputed by a statin-related increased
risk of new onset diabetes (NOD) in randomized controlled trials and meta
analyses. AREAS COVERED: This review provides an update based on recent
outstanding evidence on the statin effect on the risk of diabetes. It also
describes mechanisms potentially explaining adverse effects of statins on glucose
homeostasis. PubMed was searched for original articles and reviews published from
January 2010 (inclusive) to May 2015 (inclusive), which include the Search terms
statins, diabetes, glucose, and insulin. NOD risk seems to be more relevant with
high-intensity rather than with low-intensity statin treatment. Also, this risk
is particularly increased in patients at risk for the development of diabetes. It
appears that statins adversely affect glucose homeostasis in parallel with their
3-hydroxy-3-methylglutaryl-coenzyme A inhibition capacity. It was suggested that
lipophilic statins are more diabetogenic than the hydrophilic ones. Mechanisms
explaining statin diabetogeneicity include impaired insulin secretion by
pancreatic beta cells together with increased insulin resistance of various
tissues. EXPERT OPINION: The CV outcome benefits from statin use outweigh the
diabetes menace. However, patients at risk for the development of diabetes should
be prescribed statins with caution.
PMID- 26437129
TI - ResQ: An Approach to Unified Estimation of B-Factor and Residue-Specific Error in
Protein Structure Prediction.
AB - Computer-based structure prediction becomes a major tool to provide large-scale
structure models for annotating biological function of proteins. Information of
residue-level accuracy and thermal mobility (or B-factor), which is critical to
decide how biologists utilize the predicted models, is however missed in most
structure prediction pipelines. We developed ResQ for unified residue-level model
quality and B-factor estimations by combining local structure assembly variations
with sequence-based and structure-based profiling. ResQ was tested on 635 non
redundant proteins with structure models generated by I-TASSER, where the average
difference between estimated and observed distance errors is 1.4A for the
confidently modeled proteins. ResQ was further tested on structure decoys from
CASP9-11 experiments, where the error of local structure quality prediction is
consistently lower than or comparable to other state-of-the-art predictors.
Finally, ResQ B-factor profile was used to assist molecular replacement, which
resulted in successful solutions on several proteins that could not be solved
from constant B-factor settings.
PMID- 26437130
TI - Phenolic compounds from red wine and coffee are associated with specific
intestinal microorganisms in allergic subjects.
AB - The dietary modulation of gut microbiota, suggested to be involved in allergy
processes, has recently attracted much interest. While several studies have
addressed the use of fibres to modify intestinal microbial populations,
information about other components, such as phenolic compounds, is scarce. The
aim of this work was to identify the dietary components able to influence the
microbiota in 23 subjects suffering from rhinitis and allergic asthma, and 22 age
and sex-matched controls. The food intake was recorded by means of an annual
food frequency questionnaire. Dietary fibre tables were obtained from Marlett et
al., and the Phenol-Explorer database was used to assess the phenolic compound
intake. The quantification of microbial groups was performed using an Ion Torrent
16S rRNA gene-based analysis. The results showed a direct association between the
intake of red wine, a source of stilbenes, and the relative abundance of
Bacteroides, and between the intake of coffee, rich in phenolic acids, and the
abundance of Clostridium, Lactococcus and Lactobacillus genera. Despite
epidemiological analyses not establishing causality, these results support the
association between polyphenol-rich beverages and faecal microbiota in allergic
patients.
PMID- 26437132
TI - To Make a Difference.
AB - Disengagement causes a host of problematic behaviors that can lead to poor staff
performance and patient safety or quality issues. There are 2 broad kinds of
engagement: individual and organizational; this Editorial is about individual
engagement.
PMID- 26437131
TI - Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior.
AB - Brain microinjection can aid elucidation of the molecular substrates of complex
behaviors, such as motivation. For this purpose rodents can serve as appropriate
models, partly because the response to behaviorally relevant stimuli and the
circuitry parsing stimulus-action outcomes is astonishingly similar between
humans and rodents. In studying molecular substrates of complex behaviors, the
microinjection of reagents that modify, augment, or silence specific systems is
an invaluable technique. However, it is crucial that the microinjection site is
precisely targeted in order to aid interpretation of the results. We present a
method for the manufacture of surgical implements and microinjection needles that
enables accurate microinjection and unlimited customizability with minimal cost.
Importantly, this technique can be successfully completed in awake rodents if
conducted in conjunction with other JoVE articles that covered requisite surgical
procedures. Additionally, there are many behavioral paradigms that are well
suited for measuring motivation. The progressive ratio is a commonly used method
that quantifies the efficacy of a reinforcer to maintain responding despite an
(often exponentially) increasing work requirement. This assay is sensitive to
reinforcer magnitude and pharmacological manipulations, which allows reinforcing
efficacy and/ or motivation to be determined. We also present a straightforward
approach to program operant software to accommodate a progressive ratio
reinforcement schedule.
PMID- 26437133
TI - What Case Managers Should Know About Their Roles and Functions: A National Study
From the Commission for Case Manager Certification: Part 1.
AB - PURPOSE: The purpose of this national role and function study was to identify the
essential activities and necessary knowledge areas for effective case manager
practice from the perspective of those currently functioning in various care
settings and across diverse professional disciplines. PRIMARY PRACTICE
SETTING(S): The national study covered all case management practices and/or work
settings across the full continuum of health care. METHODOLOGY AND SAMPLE: This
cross-sectional descriptive study used the practice analysis method and online
survey research design. It employed a purposive sample of case managers, in which
52,370 individuals received an invitation to participate. Data collection
completed over a 4-week period, resulting in 7,668 useable survey responses
(nearly a 15% response rate). RESULTS: The study identified the common activities
and knowledge areas necessary for competent and effective performance of case
managers, as is highlighted in this article, which is the first of a 2-part
series on the role and function study. The results informed the needed update of
the test specifications for the Certified Case Manager (CCM) certification
examination, as will be delineated in Part 2 of the article series, to ensure
that it continues to be substantiated in current practice. Of special note are
the emergence of specific activity and knowledge domains in the area of case
management ethical, legal, and practice standards, and an increase in the number
of employers requiring certified case managers to fill vacant positions and
compensating them financially for such qualifications. IMPLICATIONS FOR CASE
MANAGEMENT PRACTICE: This study helps keep the CCM credentialing examination
evidence-based and maintain its validity for evaluating competency of case
managers. Specifically, the study identified essential activities and knowledge
domains that define competent case management practice. Findings can be used for
developing programs and curricula for the training and development of case
managers. The study instrument also can be used for further research of case
management practice.
PMID- 26437135
TI - Interdisciplinary Rounds: The Key to Communication, Collaboration, and Agreement
on Plan of Care.
AB - PURPOSE/OBJECTIVES: In the era of Pay for Performance, multiple auditing
entities, and shorter length of stays, Interdisciplinary Rounds are the future of
hospital care. This article seeks to take a broad look at this tool in its
current and historical perspective and examine how it can provide a stable
foundation for improved physician-nurse communication, agreement on the plan of
care, successful care transitions, and improvements in quality metrics, and
reduced length of stay. These rounds reflect the changing attitudes of nurses and
physicians toward a more collaborative cooperation, and teamwork, in the delivery
of patient care. When supported by strong, visible leadership, they can transform
not only direct patient care, but the perception of that care by the patient,
families, and caregivers. PRIMARY PRACTICE SETTING: Acute care hospitals.
FINDINGS AND CONCLUSIONS: Properly executed, Interdisciplinary Rounds improve
communication among the health care team and provide a basis for agreement upon
the plan of care. IMPLICATIONS FOR CASE MANAGEMENT: Case management is a logical
and frequent choice for a leadership role in Interdisciplinary Rounds. Creating a
sustainable culture that drives improved clinical care delivery and reduces
readmissions and length of stay requires efforts to ensure clear, concise care
transitions. With hospitalist programs and nursing care shifts spanning 12 hr,
and several days' off between work days, case management continues to be one of
the few constant members of the health care team-often with more knowledge of the
episode of care than even the current attending physician. Embracing rounds is a
change for the better.
PMID- 26437137
TI - Monitoring Resource Utilization in a Health Care Coordination Program.
AB - PURPOSE OF THE STUDY: This initial article describes the development of a health
care coordination intervention and documentation system designed using the Agency
for Healthcare Research and Quality (AHRQ) Care Coordination Atlas framework for
Centers for Medicare & Medicaid-funded innovation project, Leveraging Information
Technology to Guide High-Tech, High-Touch Care (LIGHT). PRIMARY PRACTICE
SETTING(S): The study occurred at an academic medical center that serves 114
counties. Twenty-five registered nurse care managers (NCMs) were hired to work
with 137 providers in 10 family community and internal medicine clinics.
METHODOLOGY AND SAMPLE: Patients were allocated into one of the four tiers on the
basis of their chronic medical conditions and health care utilization. Using a
documentation system on the basis of the AHRQ domains developed for this study,
time and touch data were calculated for 8,593 Medicare, Medicaid, or dual
eligible patients. RESULTS: We discovered through the touch and time analysis
that the majority of health care coordination activity occurred in the AHRQ
domains of communication, assess needs and goals, and facilitate transitions,
accounting for 79% of the NCM time and 61% of the touches. As expected,
increasing tier levels resulted in increased use of NCM resources. Tier 3
accounted for roughly 16% of the patients and received 159 minutes/member (33% of
total minutes), and Tier 4 accounted for 4% of patients and received 316
minutes/member (17% of all minutes). In contrast Tier 2, which did not require
routine touches per protocol, had 5,507 patients (64%), and those patients
received 5,246 hours of health care coordination, or 57 minutes/member, and took
48% of NCM time. IMPLICATIONS FOR CASE MANAGEMENT: 1. The AHRQ Care Coordination
Atlas offered a systematic way to build a documentation system that allowed for
the extraction of data that was used to calculate the amount of time and the
number of touches that NCMs delivered per member. 2. Using a framework to
systematically guide the work of health care coordination helped NCMs to think
strategically about the care being delivered, and has implications for improving
coordination of care. 3. For the purpose of reimbursement and communication with
payers about quality metrics, it is vital that the type of touches and amount of
time spent in delivering care coordination be documented in a manner that can be
easily retrieved to guide practice decisions.
PMID- 26437138
TI - The Importance of Saying What We Mean.
PMID- 26437139
TI - The Affordable Care Act: Impact on Case Managers.
PMID- 26437140
TI - What the CCMC Role and Function Study Tells You About Changes in Case Management.
PMID- 26437141
TI - Caring for the Uninsured, Undocumented Population: Challenges of Chronic Disease
Management and Access to Care.
PMID- 26437142
TI - Relational closeness moderates the association between maternal overcontrol and
children's depressive symptoms.
AB - Though numerous studies have examined the relationship between parental
overcontrol (OC) and child anxiety, few have examined the association between OC
and children's depressive symptoms. However, there are conceptual reasons to
believe that overcontrolling parenting may also be relevant to depressive
symptomatology, as well as to anticipate that other aspects of the parent-child
relationship may moderate the association between the two. In this study we
examine the association between self-reported maternal OC and child depressive
symptoms, as moderated by multiple indicators of closeness within the parent
child relationship. An ethnically and socioeconomically diverse sample of
children (N = 106, M(age) = 10.27 years) and their mothers participated in this
cross-sectional study. Mothers reported on their overcontrolling parenting and
children reported on their depressive symptoms. Children and mothers participated
in structured interviews that were analyzed for we-talk, a behavioral measure of
closeness; they also self-reported their closeness. Results indicated that child
we-talk, child self-reported closeness, and maternal we-talk moderated the
association between maternal OC and child depressive symptoms, such that OC and
depressive symptoms were positively associated only at low levels of relational
closeness. The results provide initial evidence for an association between
parental OC and child depressive symptoms, and point to the need for more
research on the role of children's perceptions in moderating the association
between parenting and child depressive symptoms.
PMID- 26437143
TI - Determinants of father involvement with young children: Evidence from the Early
Childhood Longitudinal Study-Birth Cohort.
AB - The current study used data from the Early Childhood Longitudinal Study-Birth
Cohort (ECLS-B; Snow et al., 2007) to explore determinants of resident father
involvement. Families (N = 2,900) were measured at 3 time points (9 months, 2
years, and 4 years of age). Father, mother, and child factors were examined in
relation to father caregiving and play. Latent change score models indicated that
fathers engaged in more caregiving and play behaviors and increased at a faster
rate when they more strongly identified with their role as a father. Fathers
engaged in more caregiving when mothers reported higher depressive symptoms and
increased in play more slowly when marital conflict was higher. In addition, a
Mother Depressive Symptoms * Marital Conflict interaction emerged indicating that
fathers differed in their levels of caregiving depending on mothers' report of
depressive symptoms, but only when marital conflict was low. Fathers also
increased in caregiving at a faster rate with girls than boys. A comprehensive
framework for examining resident father involvement is presented.
PMID- 26437145
TI - The effects of parental sensitivity and involvement in caregiving on mother
infant and father-infant attachment in a Portuguese sample.
AB - In the present longitudinal study, we investigated attachment quality in
Portuguese mother-infant and in father-infant dyads, and evaluated whether
attachment quality was related to parental sensitivity during parent-infant
social interaction or to the amount of time each parent spent with the infant
during play and in routine caregiving activities (e.g., feeding, bathing, play).
The sample consisted of 82 healthy full-term infants (30 girls, 53 boys, 48 first
born), and their mothers and fathers from mostly middle-class households. To
assess parental sensitivity, mothers and fathers were independently observed
during free play interactions with their infants when infants were 9 and 15
months old. The videotaped interactions were scored by masked coders using the
Crittenden's CARE-Index. When infants were 12 and 18 months old, mother-infant
and father-infant dyads were videotaped during an adaptation of Ainsworth's
Strange Situation. Parents also described their level of involvement in infant
caregiving activities using a Portuguese version of the McBride and Mills Parent
Responsibility Scale. Mothers were rated as being more sensitive than fathers
during parent-infant free play at both 9 and 15 months. There also was a higher
prevalence of secure attachment in mother-infant versus father-infant dyads at
both 12 and 18 months. Attachment security was predicted by the amount of time
mothers and fathers were involved in caregiving and play with the infant, and
with parents' behavior during parent-infant free play.
PMID- 26437144
TI - Relationship of service members' deployment trauma, PTSD symptoms, and
experiential avoidance to postdeployment family reengagement.
AB - This research examined whether military service members' deployment-related
trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and experiential
avoidance are associated with their observed levels of positive social
engagement, social withdrawal, reactivity-coercion, and distress avoidance during
postdeployment family interaction. Self reports of deployment related trauma,
postdeployment PTSD symptoms, and experiential avoidance were collected from 184
men who were deployed to the Middle East conflicts, were partnered, and had a
child between 4 and 13 years of age. Video samples of parent-child and partner
problem solving and conversations about deployment issues were collected, and
were rated by trained observers to assess service members' positive engagement,
social withdrawal, reactivity-coercion, and distress avoidance, as well as spouse
and child negative affect and behavior. Service members' experiential avoidance
was reliably associated with less observed positive engagement and more observed
withdrawal and distress avoidance after controlling for spouse and child negative
affect and behavior during ongoing interaction. Service members' experiential
avoidance also diminished significant associations between service members' PTSD
symptoms and their observed behavior. The results are discussed in terms of how
service members' psychological acceptance promotes family resilience and adaption
to the multiple contextual challenges and role transitions associated with
military deployment. Implications for parenting and marital interventions are
described.
PMID- 26437146
TI - Manifestations of Insomnia in Sleep Apnea: Implications for Screening and
Treatment.
AB - The aims of this study were to examine the presence, type, and severity of
insomnia complaints in obstructive sleep apnea (OSA) patients and to assess the
utility of the Sleep Symptom Checklist (SSC) for case identification in primary
care. Participants were 88 OSA patients, 57 cognitive-behavioral therapy for
insomnia (CBT-I) patients, and 14 healthy controls (Ctrl). Each completed a sleep
questionnaire as well as the SSC, which includes insomnia, daytime functioning,
psychological, and sleep disorder subscales. Results showed that OSA patients
could be grouped according to 3 insomnia patterns: no insomnia (OSA), n = 21;
insomnia (OSA-I), n = 30, with a subjective complaint and disrupted sleep; and
noncomplaining poor sleepers (OSA-I-NC), n = 37. Comparisons among the OSA, CBT
I, and Ctrl groups demonstrate distinct profiles on the SSC subscales, indicating
its potential utility for both case identification and treatment planning.
PMID- 26437147
TI - Transactive goal dynamics.
AB - Transactive goal dynamics (TGD) theory conceptualizes 2 or more interdependent
people as 1 single self-regulating system. Six tenets describe the nature of goal
interdependence, predict its emergence, predict when it will lead to positive
goal outcomes during and after the relationship, and predict the consequences for
the relationship. Both partners in a TGD system possess and pursue self-oriented,
partner-oriented, and system-oriented goals, and all of these goals and pursuits
are interdependent. TGD theory states that relationship partners' goals, pursuit,
and outcomes affect each other in a dense network of goal interdependence,
ultimately becoming so tightly linked that the 2 partners are most accurately
conceptualized as components within a single self-regulating system.
PMID- 26437148
TI - Rehearsal in serial recall: An unworkable solution to the nonexistent problem of
decay.
AB - We examine the explanatory roles that have been ascribed to various forms of
rehearsal or refreshing in short-term memory (STM) and working memory paradigms,
usually in conjunction with the assumption that memories decay over time if they
are not rehearsed. Notwithstanding the popularity of the rehearsal notion, there
have been few detailed examinations of its underlying mechanisms. We explicitly
implemented rehearsal in a decay model and explored its role by simulation in
several benchmark paradigms ranging from immediate serial recall to complex span
and delayed recall. The results show that articulatory forms of rehearsal often
fail to counteract temporal decay. Rapid attentional refreshing performs
considerably better, but so far there is scant empirical evidence that people
engage in refreshing during STM tasks. Combining articulatory rehearsal and
refreshing as 2 independent maintenance processes running in parallel leads to
worse performance than refreshing alone. We conclude that theoretical reliance on
articulatory rehearsal as a causative agent in memory may be unwise and that
explanatory appeals to rehearsal are insufficient unless buttressed by
quantitative modeling.
PMID- 26437149
TI - An improved probabilistic account of counterfactual reasoning.
AB - When people want to identify the causes of an event, assign credit or blame, or
learn from their mistakes, they often reflect on how things could have gone
differently. In this kind of reasoning, one considers a counterfactual world in
which some events are different from their real-world counterparts and considers
what else would have changed. Researchers have recently proposed several
probabilistic models that aim to capture how people do (or should) reason about
counterfactuals. We present a new model and show that it accounts better for
human inferences than several alternative models. Our model builds on the work of
Pearl (2000), and extends his approach in a way that accommodates backtracking
inferences and that acknowledges the difference between counterfactual
interventions and counterfactual observations. We present 6 new experiments and
analyze data from 4 experiments carried out by Rips (2010), and the results
suggest that the new model provides an accurate account of both mean human
judgments and the judgments of individuals. (PsycINFO Database Record
PMID- 26437150
TI - Impaired integration in psychopathy: A unified theory of psychopathic
dysfunction.
AB - This article introduces a novel theoretical framework for psychopathy that
bridges dominant affective and cognitive models. According to the proposed
impaired integration (II) framework of psychopathic dysfunction, topographical
irregularities and abnormalities in neural connectivity in psychopathy hinder the
complex process of information integration. Central to the II theory is the
notion that psychopathic individuals are "'wired up' differently" (Hare,
Williamson, & Harpur, 1988, p. 87). Specific theoretical assumptions include
decreased functioning of the Salience and Default Mode Networks, normal
functioning in executive control networks, and less coordination and flexible
switching between networks. Following a review of dominant models of psychopathy,
we introduce our II theory as a parsimonious account of behavioral and brain
irregularities in psychopathy. The II theory provides a unified theoretical
framework for understanding psychopathic dysfunction and integrates principle
tenets of affective and cognitive perspectives. Moreover, it accommodates
evidence regarding connectivity abnormalities in psychopathy through its network
theoretical perspective. (PsycINFO Database Record
PMID- 26437151
TI - A joint model of word segmentation and meaning acquisition through cross
situational learning.
AB - Human infants learn meanings for spoken words in complex interactions with other
people, but the exact learning mechanisms are unknown. Among researchers, a
widely studied learning mechanism is called cross-situational learning (XSL). In
XSL, word meanings are learned when learners accumulate statistical information
between spoken words and co-occurring objects or events, allowing the learner to
overcome referential uncertainty after having sufficient experience with
individually ambiguous scenarios. Existing models in this area have mainly
assumed that the learner is capable of segmenting words from speech before
grounding them to their referential meaning, while segmentation itself has been
treated relatively independently of the meaning acquisition. In this article, we
argue that XSL is not just a mechanism for word-to-meaning mapping, but that it
provides strong cues for proto-lexical word segmentation. If a learner directly
solves the correspondence problem between continuous speech input and the
contextual referents being talked about, segmentation of the input into word-like
units emerges as a by-product of the learning. We present a theoretical model for
joint acquisition of proto-lexical segments and their meanings without assuming a
priori knowledge of the language. We also investigate the behavior of the model
using a computational implementation, making use of transition probability-based
statistical learning. Results from simulations show that the model is not only
capable of replicating behavioral data on word learning in artificial languages,
but also shows effective learning of word segments and their meanings from
continuous speech. Moreover, when augmented with a simple familiarity preference
during learning, the model shows a good fit to human behavioral data in XSL
tasks. These results support the idea of simultaneous segmentation and meaning
acquisition and show that comprehensive models of early word segmentation should
take referential word meanings into account. (PsycINFO Database Record
PMID- 26437152
TI - Sequential processes and the shapes of reaction time distributions.
AB - It is sometimes suggested that reaction time (RT) distributions have the same
shape across conditions or groups. In this note we show that this is highly
unlikely if the RT is the sum of the stochastically independent durations of 2 or
more stages (sequential processes) (a) that are influenced selectively by
different factors, or (b) 1 of which is influenced selectively by some factor. We
provide an example of substantial shape differences in RT data from a flash
detection experiment, data that have been shown to satisfy requirement (a).
Ignoring these requirements, we also note that in a large range of instances
reviewed by Matzke and Wagenmakers (2009) in which the ex-Gaussian distribution
was fitted to RT data from different conditions in the same experiment, most sets
of distributions fail to satisfy even a weak requirement for shape invariance. In
the Appendix we describe the Summation Test for selectively influenced stages
with independent durations (Roberts & Sternberg, 1993), and provide an example of
its application. (PsycINFO Database Record
PMID- 26437153
TI - Examining the mechanisms underlying contextual preference reversal: Comment on
Trueblood, Brown, and Heathcote (2014).
AB - Trueblood, Brown, and Heathcote (2014) provide a new model of multiattribute
choice, which accounts for 3 contextual reversal effects (similarity, attraction
and compromise). We review the details of the model and highlight some novel
predictions. First, we show that the model works by setting a "fine balance"
between 2 opposing factors that influence choice. As a result, small changes in
the attributes of choice alternatives can disturb this balance. Second, we show
that the model gives a partial account of the compromise effect. We describe a
number of experiments that could distinguish the MLBA from other models of
multiattribute choice.
PMID- 26437154
TI - The fragile nature of contextual preference reversals: Reply to Tsetsos, Chater,
and Usher (2015).
AB - Trueblood, Brown, and Heathcote (2014) developed a new model, called the
multiattribute linear ballistic accumulator (MLBA), to explain contextual
preference reversals in multialternative choice. MLBA was shown to provide good
accounts of human behavior through both qualitative analyses and quantitative
fitting of choice data. Tsetsos, Chater, and Usher (2015) investigated the
ability of MLBA to simultaneously capture 3 prominent context effects
(attraction, compromise, and similarity). They concluded that MLBA must set a
"fine balance" of competing forces to account for all 3 effects simultaneously
and that its predictions are sensitive to the position of the stimuli in the
attribute space. Through a new experiment, we show that the 3 effects are very
fragile and that only a small subset of people shows all 3 simultaneously. Thus,
the predictions that Tsetsos et al. generated from the MLBA model turn out to
match closely real data in a new experiment. Support for these predictions
provides strong evidence for the MLBA. A corollary is that a model that can
"robustly" capture all 3 effects simultaneously is not necessarily a good model.
Rather, a good model captures patterns found in human data, but cannot
accommodate patterns that are not found.
PMID- 26437155
TI - Dermatology consultations in a tertiary care hospital: A retrospective study of
243 cases.
AB - BACKGROUND: The practice of dermatology remains mainly outpatient, although
dermatologic consultations often have a large impact on inpatient care.
OBJECTIVE: To analyze the reasons for dermatologic consultation and the impact of
dermatologic evaluation at a major teaching hospital. METHODS: Retrospective
chart review of 243 consecutive dermatologic consultations from primary ward
teams between July 2012, and August 2013. RESULTS: Sixty-seven percent of the
dermatologic consults were requested by the internal medicine, intensive care
units, and hematology/oncology departments. Common skin conditions accounted for
a large majority of consultations including: infectious (24.0%), drug-related
(22.3%), and inflammatory skin conditions (21.0%). Most consultations required
only one visit for resolution (60.9%). The primary team submitted a correct
dermatologic diagnosis in 48.9% of cases. Dermatology consultation resulted in a
change in or addition to treatment in 72.4% of patients. LIMITATIONS: Our
analysis was limited by the data capture of the consulting physicians and the
reliability of the patient historian. CONCLUSIONS: Our results revealed that
common dermatoses account for a majority of dermatologic consultations. Modern
ward teams continue to struggle with promptly recognizing and appropriately
managing common skin conditions. Further training of ward physicians on common
dermatologic conditions will improve recognition and treatment of skin conditions
in hospitalized patients.
PMID- 26437156
TI - Zoledronic acid-associated symmetrical drug-related intertriginous and flexural
exanthema (SDRIFE): report of baboon syndrome in a woman with recurrent
metastatic breast cancer after receiving zoledronic acid.
AB - BACKGROUND: Baboon syndrome is a distinctive skin reaction in which the patient
typically develops erythematous buttocks that appear similar to those of a
baboon. The non-contact allergenic variant of baboon syndrome is also referred to
as symmetrical drug-related intertriginous and flexural exanthema (SDRIFE).
Zoledronic acid is a bisphosphonate that is used in patients with metastatic
cancer to prevent bone complications. PURPOSE: Zoledronic acid-associated baboon
syndrome is described in a woman with recurrent metastatic breast cancer.
METHODS: PubMed was used to search the following terms, separately and in
combination: baboon syndrome, breast cancer, symmetrical drug-related
intertriginous and flexural exanthema, and zoledronic acid. All papers were
reviewed and relevant manuscripts, along with their reference citations, were
evaluated. RESULTS: Zoledronic acid has infrequently been associated with
mucocutaneous adverse reactions. However, baboon syndrome has not previously been
observed in patients receiving zoledronic acid. The reported woman developed
baboon syndrome after her initial exposure to zoledronic acid. CONCLUSIONS: Non
contact allergenic drug-induced baboon syndrome has most commonly been associated
with antibiotics such as beta-lactams and penicillins. Zoledronic acid-associated
baboon syndrome has not previously been observed in cancer patients. Baboon
syndrome (SDRIFE variant) was observed in a woman with recurrent metastatic
breast cancer after her first exposure to zoledronic acid. In summary, SDRIFE can
occur in oncology patients receiving zoledronic acid and zoledronic acid should
be added to the list of medications associated with the potential to cause non
contact allergenic drug-induced baboon syndrome.
PMID- 26437157
TI - Subcorneal pustular dermatosis associated with Coccidioides immitis.
AB - Coccidioidomycosis (AKA "Valley fever") is a primary pulmonary infection via
airborne spores released from coccidioides immitis in the soil. Reactive
cutaneous eruptions resulting from the pulmonary infection are difficult to
diagnose because skin biopsies do not contain the organism. We present an
adolescent male with primary pulmonary C.immitis infection manifesting with
biopsy proven subcorneal pustular dermatosis. Serological studies revealed
increasingly positive titers for coccidioidomycosis and symptoms resolved
promptly following initiation of systemic antifungal therapy. Our unique case
presentation illustrates subcorneal pustular dermatosis as a reactive eruption
owing to primary pulmonary coccidioidomycosis. An association between the two
conditions warrants further investigation.
PMID- 26437158
TI - Verruciform Genital-Associated (Vegas) Xanthoma: report of a patient with
verruciform xanthoma of the scrotum and literature review.
AB - BACKGROUND: Verruciform xanthoma is a benign verrucous lesion characterized by
epithelial acanthosis and lipid-laden foamy histiocytes in the connective tissue
papillae. It typically presents as a papillomatous, polypoid, or sessile lesion.
Verruciform xanthoma is most commonly observed within the oral cavity. However,
albeit less frequently, it develops on the penis, scrotum, or vulva. PURPOSE:
We describe the clinical and pathologic findings of a man who developed a
verruciform xanthoma on his scrotum. We also summarize the associated conditions,
the differential diagnosis, the postulated pathogenesis, and the treatment
options for this tumor. MATERIALS AND METHODS: The features of a man with a
scrotal verruciform xanthoma are presented. Using PubMed, the following terms
were searched and relevant citations assessed: anogenital, foam cells, penis,
scrotum, verruciform, verruciform xanthoma, vulva, and xanthoma. In addition, the
literature on verruciform xanthoma is reviewed. RESULTS: Our patient developed
an asymptomatic, exophytic, red filiform papule on his scrotum. A shave biopsy,
attempting to remove the entire lesion, was performed. Based on correlation of
the clinical presentation and histopathologic findings, a diagnosis of
verruciform xanthoma was established. The patient applied mupirocin 2% ointment
to the biopsy site, which subsequently healed without complication or recurrence.
CONCLUSION: Verruciform xanthoma is a benign tumor commonly located within the
oral cavity and characterized by the development of a small verrucous,
papillomatous, polypoid, or sessile growth. Extraoral sites of verruciform
xanthoma often include the penis, scrotum, or vulva; we introduce the term
'Vegas' (Verruciform Genital-Associated) xanthoma for these lesions. The lesions
are often mistaken for viral warts or malignancies. Although the mechanism of
pathogenesis is unknown, verruciform xanthoma may have a multifactorial etiology
involving inflammation, local immunosuppression, and/or metabolic dysfunction. It
has also been postulated that verruciform xanthoma is a secondary reaction to
trauma-induced epithelial damage or degeneration. A biopsy for histopathologic
examination is required to diagnose verruciform xanthoma. The treatment of
verruciform xanthoma typically involves simple surgical excision.
PMID- 26437159
TI - Vesicular erythema migrans: an atypical and easily misdiagnosed form of Lyme
disease.
AB - Erythema migrans is the initial sign in the majority of patients infected with
Borrelia, the genus of spirochetes that causes Lyme disease. Early identification
and treatment decrease the risk of progression to later stages of disease.
Although a "bull's eye" appearance owing to lesional clearing is considered
classic for erythema migrans, this feature is surprisingly often lacking among
patients in the United States. Furthermore, cutaneous Lyme disease can exhibit a
wide range of morphologic variability in a minority of patients. Herein, we
describe the case of a patient with Lyme disease in which the presence of
atypical vesicular features, in conjunction with the initial absence of clearing,
resulted in multiple misdiagnoses and delayed treatment. We also review the
literature on the epidemiology and management of erythema migrans for cases in
which the diagnosis may pose a challenge.
PMID- 26437160
TI - Mycophenolate mofetil therapy for pediatric bullous pemphigoid.
AB - Bullous pemphigoid (BP) is a common autoimmune blistering disease in the adult
population, but extremely rare in the pediatric population. Childhood BP usually
has a favorable prognosis and responds well to topical and oral steroids.
However, for patients that do not respond to corticosteroids, therapeutic
alternatives are scarce. We report a case of a toddler with recalcitrant BP who
was successfully treated with mycophenolate mofetil (MMF).
PMID- 26437161
TI - Pitted keratolysis: successful management with mupirocin 2% ointment monotherapy.
AB - BACKGROUND: Pitted keratolysis is a benign dermatosis that occurs on plantar
skin. PURPOSE: We describe a man with pitted keratolysis that was successfully
treated with mupirocin 2% ointment monotherapy. METHODS AND MATERIALS: We
reviewed PubMed for the following terms: mupirocin, ointment, pitted keratolysis,
treatment. We also reviewed papers containing these terms and their references.
RESULTS: Complete resolution of pitted keratolysis occurred following monotherapy
with twice daily application of mupirocin 2% ointment for a duration of three
weeks. There was no recurrence at a follow-up visit eight weeks later.
CONCLUSIONS: Several topical and oral treatments are available to successfully
manage pitted keratolysis. Our patient confirms previous reports of pitted
keratolysis resolving with mupirocin 2% ointment treatment. Monotherapy with
mupirocin 2% ointment should be considered as a primary treatment alternative for
pitted keratolysis.
PMID- 26437162
TI - A case report of primary cutaneous marginal zone lymphoma treated with
intralesional steroids.
AB - IMPORTANCE: Primary cutaneous marginal zone lymphoma (PCMZL) is a low-grade
malignant B-cell lymphoma that appears in the skin without any extracutaneous
manifestations. Therapeutic mainstays for PCMZL have primarily included
radiotherapy and surgery. Intralesional steroids have been found to resolve the
lesions caused by PCMZL, but there is a dearth of literature regarding this
therapy indicating that this is not a commonly favored treatment option.
OBSERVATIONS: We present a case of 60-year-old woman who presented with PCMZL on
her right eyebrow. Three years later, after two courses of radiation and one
relapse, the patient presented with new lesions on both arms, consistent once
again with PCMZL. At this time, therapy with nine rounds of intralesional
triamcinolone was attempted. After each round of triamcinolone, gradual
improvement of the lesions was noted until complete resolution occurred.
CONCLUSIONS AND RELEVANCE: This case reminds practitioners that intralesional
corticosteroids can be effectively and safely used to treat localized PCMZL.
Intralesional steroids are less invasive, cheaper, and easier to administer than
the majority of other recommended therapies for PCMZL. Thus, although they are
often overlooked, intralesional corticosteroids should be more often considered
when developing a treatment plan for localized PCMZL.
PMID- 26437163
TI - Atypical propylthiouracil-induced ANCA-positive vasculitis: report of a case with
unusual clinical and histopathologic findings.
AB - The side effects of propylthiouracil, including cytopenia and vasculitis, are
well established. We present an interesting case in which cytopenia and
cutaneous vasculopathy occurred concomitantly in a critically ill patient. The
patient was initially treated for suspected infection until dermatologic and
rheumatologic workup revealed ANCA-positivity and vasculopathy on histopathology,
most consistent with an atypical presentation of ANCA-positive vasculitis. Upon
initiation of immunosuppressive therapy, the patient's condition rapidly improved
emphasizing the importance of early recognition of this condition.
PMID- 26437165
TI - Primary care providers' perceptions of mobile store-and-forward teledermatology.
AB - INTRODUCTION: Although teledermatology offers promise as a tool to increase
access to care, adoption has been limited. Understanding the perspectives and
experiences of key stakeholders, such as primary care providers (PCPs) and
patients, is important to identify opportunities to reduce barriers to adoption
and to improve teledermatology programs. Although many studies have examined
patients' experiences and satisfaction with teledermatology, few have examined
referring PCPs' perspectives. OBJECTIVE: To identify PCPs' perceptions on the
strengths and limitations of teledermatology in order to identify opportunities
to improve teledermatology programs. METHODS: We distributed an anonymous, web
based survey to 30 PCPs involved in a two-year study evaluating a mobile app
based teledermatology platform. RESULTS: 100% (18/18) agreed or strongly agreed
that teledermatology increases access to dermatologic care, improves patient
care, and is acceptable to patients. 100% (18/18) agreed or strongly agreed that
teledermatology provides educational benefit to the PCP. Only 6% (1/18) agreed
that teledermatology increases medical liability and 11% (2/18) agreed that it
increases risk of a breach in privacy or confidentiality. CONCLUSIONS: Our
findings highlight that PCPs are highly satisfied with mobile app-based, store
and-forward teledermatology and that they believe teledermatology offers
synergistic educational benefit. We hope these results will help guide the
development of teledermatology programs to increase access to timely, cost
effective care.
PMID- 26437164
TI - Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic
leukemia cutis.
AB - Leukemia cutis describes cutaneous lesions produced by infiltrates of leukemic
cells. It usually manifests contemporaneously with the initial diagnosis of
systemic leukemia, but may also precede or follow systemic leukemia. Most cases
are associated with acute myeloid leukemia. Adult B-cell lymphoblastic leukemia
cutis is very rare. We report a 59-year-old woman with a history of B-cell acute
lymphoblastic leukemia who relapsed with aleukemic lymphoblastic leukemia cutis.
Lymphoglandular bodies were conspicuous on biopsy and may serve as a morphologic
clue to lymphocytic differentiation while molecular and immunophenotypic studies
are pending. The patient was successfully treated with local radiation therapy
and oral ponatinib.
PMID- 26437166
TI - A rare case of trigeminal trophic syndrome with an extensive scalp, forehead, and
upper eyelid ulceration in a patient with undiagnosed Alzheimer disease.
AB - BACKGROUND: Trigeminal Trophic Syndrome (TTS) is a rare presentation of facial
ulceration, which is characterized by the triad of anesthesia, paraesthesia, and
damage of trigeminal sensory branches. MAIN OBSERVATIONS: We report a unique case
of TTS as an extensive forehead and scalp ulceration in a patient with
undiagnosed Alzheimer disease. CONCLUSIONS: Treatment options for trigeminal
trophic syndrome are limited and disappointing especially in older patients with
dementia. Family education and behavioral modification therapies may be well
tolerated option in this population.
PMID- 26437167
TI - A case report of crusted scabies in an adult patient with Down syndrome.
AB - IMPORTANCE: Crusted (Norwegian) scabies is a severe manifestation of the
contagious skin infection caused by Sarcoptes scabiei. Crusted scabies has been
well described in patients with known immunocompromised states. Treatment may be
complicated by delayed diagnosis and/or inadequate treatment. This infection may
not rank highly on one's differential diagnosis in the absence of an
immunocompromised state, highlighting the uniqueness of the case being presented.
Several papers describe immunocompromised children with Down syndrome who are
infected with crusted scabies. We present a case of infection in an adult with
Down syndrome without evidence of an immunocompromised state. OBSERVATIONS: Our
patient came to us with a 13-month history of progressively worsening symptoms,
the last 4-6 weeks of that time period being most dramatic, despite various
treatments. We performed tissue biopsy, culture, and laboratory evaluations,
which revealed numerous mites and bacterial superinfection. CONCLUSIONS AND
RELEVANCE: Crusted scabies infection may occur in adult age individuals with Down
syndrome regardless of immune status, leading us to encourage practitioners to
consider this condition when presented with patients of this population. We also
highlight the need for further exploration of disease prevalence in this patient
population.
PMID- 26437168
TI - Successful treatment of palmoplantar pustulosis with isotretinoin.
AB - IMPORTANCE: Variably considered as a localized subtype of pustular psoriasis,
palmoplantar pustulosis (PPP) is commonly treated with topical steroids,
acitretin, and local phototherapy with oral or topical psoralen (PUVA). The
utility of acitretin for PPP is limited by adverse effects such as myalgias and
an extended risk of teratogenicity in female patients. Isotretinoin is a more
tolerable retinoid with a shorter teratogenic window, but to date its
effectiveness in PPP has not been reported. Herein we present two patients with
PPP who responded well to isotretinoin treatment. OBSERVATIONS: Two patients with
PPP refractory to topical therapies were started on acitretin. Both patients
developed adverse effects (including headache, myalgias, and mood alterations)
leading to acitretin discontinuation. Isotretinoin monotherapy was started in one
patient resulting in significant clearing of palmar plaques and scale, and the
addition of isotretinoin to UVA therapy resulted in near-complete clearing of
recalcitrant plantar plaques in the second patient. CONCLUSIONS AND RELEVANCE:
Acitretin represents an important treatment for PPP, but is limited by adverse
effects and extended teratogenicity. Our experience supports the utility of
isotretinoin as a potential therapeutic alternative, which may be particularly
beneficial in patients who are poor candidates for or unable to tolerate
acitretin therapy.
PMID- 26437169
TI - Acne isolated within a Becker nevus of a 14 year-old girl.
AB - Becker nevus (BN) is a common benign condition occurring most often in young men,
much more often than in women. Acne isolated within a BN is a rare phenomenon
hypothesized to occur, at least in part, due to increased androgen sensitivity
within the nevus. We present a rare case of papular acne with in a BN of a 14
year-old girl.
PMID- 26437170
TI - Nicolau syndrome following intramuscular injection of oxytocin in pregnant women:
report of two cases.
AB - Nicolau syndrome, also known as embolia cutis medicamentosa, is a well known but
very rare complication occuring after intramuscular drug injections and
presenting with local intense pain. Immediately after injection the skin blanches
and within minutes to hours an erythematous macule develops, which evolves into a
livedoid violaceous patch with dendrites. This condition is initially
hemorrhagic, then it ulcerates, and eventually heals with an atrophic scar. Many
different drugs have been reported to cause Nicolau syndrome . To date there have
been no reports of Nicolau syndrome caused by intramuscular oxytocin injection.
We would like to report two cases that occured after intramuscular injection of
oxytocin.
PMID- 26437171
TI - Flagellate shiitake mushroom dermatitis.
AB - An 84-year-old woman presented with 5 days of a pruritic skin eruption that
formed arciform and linear patterns. She was diagnosed with flagellate shiitake
mushroom dermatitis related to shiitake mushroom consumption the day prior
symptom onset.
PMID- 26437172
TI - Isolation of Leclercia adecarboxylata from a patient with a subungual splinter.
AB - Leclercia adecarboxylata is a rarely described motile, aerobic, gram-negative
bacillus reported to cause clinically significant solitary infections in
immunocompromised patients and polymicrobial wound infections in immunocompetent
patients [1-5]. We present a case of a polymicrobial infection including L.
adecarboxylata in a healthy female patient with a subungual splinter, to increase
awareness and aid in the diagnosis and treatment of cutaneous L. adecarboxylata
infections. To our knowledge, this is the first reported case of trauma-related
subungual L. adecarboxylata infection reported in the dermatology literature.
PMID- 26437173
TI - Phosphorescent Zinc Probe for Reversible Turn-On Detection with Bathochromically
Shifted Emission.
AB - Phosphorescent molecules are attractive complements to fluorescent compounds for
bioimaging. Time-gated acquisition of the long-lived phosphorescence signals
provides an effective means to eliminate unwanted background noises due to short
lived autofluorescence. We have previously investigated the molecular principles
governing modulation of photoinduced electron transfer in phosphorescence zinc
probes that were based on biscyclometalated Ir(III) complexes (Woo, H. et al. J.
Am. Chem. Soc. 2013, 135, 4771-4787). The studies established that
phosphorescence turn-on responses would be attainable for Ir(III) complexes with
high triplet-state energies. This sets an upper limit to an emission wavelength,
restricting the development of red- or near-IR-phosphorescence turn-on probes. To
address this challenge, we designed and synthesized a new phosphorescent probe
having an electron-deficient 2-(2-pyridyl)pyrazine diimine ligand tethering a
di(2-picolyl)amine (DPA) zinc receptor. This ligand control led to red
phosphorescence emission (lambda(ems) = 596 nm), with an excited-state reduction
potential (E*(red)) retained as high as 1.44 V versus standard calomel electrode
(SCE). The E*(red) value was more positive than the ground-state oxidation
potential of DPA (1.05 V vs SCE), permitting an occurrence of photoinduced
electron transfer at a rate of 2 * 10(7) s(-1). Zinc binding at DPA abolished the
electron transfer to produce phosphorescence turn-on signaling. The probe was
capable of detecting zinc ions selectively over other competing biological metal
ions in aqueous buffer solutions (pH 7.4, 20 mM piperazine-N,N'-bis(2
ethanesulfonic aid)) with the zinc dissociation constant of 109 pM. Finally,
bioimaging utility of the probe has been successfully demonstrated by visualizing
exogenously supplied zinc ions in live HeLa cells. The research described in this
paper demonstrates that judicious ligand control enables retention of turn-on
responses in the low-energy phosphorescence region.
PMID- 26437174
TI - Postapplication Fipronil Exposure Following Use on Pets.
AB - Fipronil is a pyrazole acaricide and insecticide that may be used for insect,
tick, lice, and mite control on pets. Residents' short-term and long-term
postapplication exposures to fipronil, including secondary environmental
exposures, were estimated using data from chemical-specific studies. Estimations
of acute (24-h) absorbed doses for residents were based on U.S. Environmental
Protection Agency (U.S. EPA) 2012 standard operating procedures (SOPs) for
postapplication exposure. Chronic exposures were not estimated for residential
use, as continuous, long-term application activities were unlikely to occur.
Estimated acute postapplication absorbed doses were as high as 0.56 MUg/kg-d for
toddlers (1-2 yr) in households with treated pets based on current U.S. EPA SOPs.
Acute toddler exposures estimated here were fivefold larger in comparison to
adults. Secondary exposure from the household environment in which a treated pet
lives that is not from contacting the pet, but from contacting the house interior
to which pet residues were transferred, was estimated based on monitoring socks
worn by pet owners. These secondary exposures were more than an order of
magnitude lower than those estimated from contacting the pet and thus may be
considered negligible.
PMID- 26437176
TI - Sharpshooting in sport science and elite sports training.
PMID- 26437175
TI - Brightness-equalized quantum dots.
AB - As molecular labels for cells and tissues, fluorescent probes have shaped our
understanding of biological structures and processes. However, their capacity for
quantitative analysis is limited because photon emission rates from multicolour
fluorophores are dissimilar, unstable and often unpredictable, which obscures
correlations between measured fluorescence and molecular concentration. Here we
introduce a new class of light-emitting quantum dots with tunable and equalized
fluorescence brightness across a broad range of colours. The key feature is
independent tunability of emission wavelength, extinction coefficient and quantum
yield through distinct structural domains in the nanocrystal. Precise tuning
eliminates a 100-fold red-to-green brightness mismatch of size-tuned quantum dots
at the ensemble and single-particle levels, which substantially improves
quantitative imaging accuracy in biological tissue. We anticipate that these
materials engineering principles will vastly expand the optical engineering
landscape of fluorescent probes, facilitate quantitative multicolour imaging in
living tissue and improve colour tuning in light-emitting devices.
PMID- 26437177
TI - The Cyclooctadepsipeptide Anthelmintic Emodepside Differentially Modulates
Nematode, Insect and Human Calcium-Activated Potassium (SLO) Channel Alpha
Subunits.
AB - The anthelmintic emodepside paralyses adult filarial worms, via a mode of action
distinct from previous anthelmintics and has recently garnered interest as a new
treatment for onchocerciasis. Whole organism data suggest its anthelmintic action
is underpinned by a selective activation of the nematode isoform of an
evolutionary conserved Ca2+-activated K+ channel, SLO-1. To test this at the
molecular level we compared the actions of emodepside at heterologously expressed
SLO-1 alpha subunit orthologues from nematode (Caenorhabditis elegans),
Drosophila melanogaster and human using whole cell voltage clamp. Intriguingly we
found that emodepside modulated nematode (Ce slo-1), insect (Drosophila, Dm slo)
and human (hum kcnma1)SLO channels but that there are discrete differences in the
features of the modulation that are consistent with its anthelmintic efficacy.
Nematode SLO-1 currents required 100 MUM intracellular Ca2+ and were strongly
facilitated by emodepside (100 nM; +73.0 +/- 17.4%; n = 9; p < 0.001). Drosophila
Slo currents on the other hand were activated by emodepside (10 MUM) in the
presence of 52 nM Ca2+ but were inhibited in the presence of 290 nM Ca2+ and
exhibited a characteristic loss of rectification. Human Slo required 300 nM Ca2+
and emodepside transiently facilitated currents (100 nM; +33.5 +/- 9%; n = 8;
p<0.05) followed by a sustained inhibition (-52.6 +/- 9.8%; n = 8; p < 0.001).
This first cross phyla comparison of the actions of emodepside at nematode,
insect and human channels provides new mechanistic insight into the compound's
complex modulation of SLO channels. Consistent with whole organism behavioural
studies on C. elegans, it indicates its anthelmintic action derives from a strong
activation of SLO current, not observed in the human channel. These data provide
an important benchmark for the wider deployment of emodepside as an anthelmintic
treatment.
PMID- 26437178
TI - Stimuli-Responsive Cubosomes Formed from Blue Phase Liquid Crystals.
AB - Cubosomes formed from blue phase liquid crystals (BPs) dispersed in aqueous media
exhibit optical responses to biological amphiphiles. In this study, the formation
of aqueous dispersions of BPs is reported, and the effects of confinement and
lipids on the phase behavior, optical appearance, and morphology of BP droplets
are characterized.
PMID- 26437180
TI - Geographical diffusion of prazosin across Veterans Health Administration:
Examination of regional variation in daily dosing and quality indicators among
veterans with posttraumatic stress disorder.
AB - Posttraumatic stress disorder (PTSD) is a high-priority treatment area for the
Veterans Health Administration (VHA), and dissemination patterns of innovative,
efficacious therapies can inform areas for potential improvement of diffusion
efforts and quality prescribing. In this study, we replicated a prior examination
of the period prevalence of prazosin use as a function of distance from Puget
Sound, Washington, where prazosin was first tested as an effective treatment for
PTSD and where prazosin use was previously shown to be much greater than in other
parts of the United States. We tested the following three hypotheses related to
prazosin geographic diffusion: (1) a positive geographical correlation exists
between the distance from Puget Sound and the proportion of users treated
according to a guideline recommended minimum therapeutic target dose (>/=6 mg/d),
(2) an inverse geographic correlation exists between prazosin and benzodiazepine
use, and (3) no geographical correlation exists between prazosin use and
serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor
(SSRI/SNRI) use. Among a national sample of veterans with PTSD, overall prazosin
utilization increased from 5.5 to 14.8% from 2006 to 2012. During this time
period, rates at the Puget Sound VHA location declined from 34.4 to 29.9%,
whereas utilization rates at locations a minimum of 2,500 miles away increased
from 3.0 to 12.8%. Rates of minimum target dosing fell from 42.6 to 34.6% at the
Puget Sound location. In contrast, at distances of at least 2,500 miles from
Puget Sound, minimum threshold dosing rates remained stable (range, 18.6 to
17.7%). No discernible association was demonstrated between SSRI/SNRI or
benzodiazepine utilization and the geographic distance from Puget Sound. Minimal
threshold dosing of prazosin correlated positively with increased diffusion of
prazosin use, but there was still a distance diffusion gradient. Although
prazosin adoption has improved, geographic differences persist in both
prescribing rates and minimum target dosing. Importantly, these regional
disparities appear to be limited to prazosin prescribing and are not meaningfully
correlated with SSRI/SNRI and benzodiazepine use as indicators of PTSD
prescribing quality.
PMID- 26437179
TI - Combination therapy with zoledronic acid and cetuximab effectively suppresses
growth of colorectal cancer cells regardless of KRAS status.
AB - Targeted molecular therapy is an effective anticancer strategy. Anti-EGFR
monoclonal antibodies such as cetuximab (CTX) have been approved for the
treatment of various malignancies, including colorectal cancer (CRC) with wild
type KRAS. However, their efficacy in patients with KRAS mutations has not been
established. Therefore, we investigated whether CTX treatment was effective as a
single agent or in combination with zoledronic acid (ZOL) in human CRC cell lines
with different KRAS status. CRC cell lines SW48 (wild-type KRAS) and LS174T
(mutant KRAS) were treated with ZOL, CTX and a combination of both drugs.
Cytotoxicity was measured using the MTT assay. Changes in the levels of
intracellular signaling proteins were evaluated using western blot analysis.
Finally, we evaluated the efficacy of the combination treatment in an in vivo
xenograft model. We observed that ZOL apparently inhibited growth in both cell
lines, whereas CTX showed little effect. ZOL also increased the levels of
unprenylated RAS. Combined ZOL and CTX treatment was synergistic in both cell
lines and was associated with inhibition of the RAS-MAPK and AKT-mTOR signaling
pathways. Furthermore, the combination treatment was more effective in
suppressing the growth of xenografts derived from both SW48 and LS174T cells;
this effect was associated with increased apoptosis. These results demonstrate
that ZOL inhibits the growth of colon cancer cells regardless of KRAS status, and
combination therapy using ZOL and CTX enhances this growth suppression. These
findings suggest a novel strategy for the treatment of CRC independent of KRAS
mutational status.
PMID- 26437181
TI - Bet v 1- and Bet v 2-Associated Plant Food Sensitization in Uganda and Germany:
Differences and Similarities.
AB - BACKGROUND: Birch pollen allergy and concomitant plant food sensitization are
well documented in Europe. However, there are currently no data available on
pollen-associated plant food sensitization or even pollen allergy in tropical
Africa. Our study aimed to investigate Bet v 1- and Bet v 2-associated plant food
sensitization in atopic patients from Uganda and compare it with sensitization
rates in German patients. METHODS: Sera from 83 Ugandan and 97 German atopic
patients were analysed using UniCAP100TM for allergen-specific IgE against the
birch tree pollen allergens Bet v 1 and Bet v 2 as well as the plant foods
hazelnut, apple, kiwi, pea, peach, cherry, litchi, peanut, and soy. RESULTS: As
expected, sensitization to Bet v 1 and cross-reactive plant food allergens was
more common in German atopic patients. In contrast, the prevalence of
sensitization against Bet v 2 was remarkably similar in Ugandan and German
patients. Interestingly, in Ugandan patients we found IgE-mediated sensitization
against plant foods such as hazelnut, pea, peach, cherry, and litchi that are
neither cultivated nor consumed in Uganda. CONCLUSIONS: For Ugandan atopic
patients, sensitization against the Bet v 2 allergen (a plant profilin) may
explain cross-reactivity to several plant foods which are not consumed in Uganda.
Additionally, it is probable that sensitization of Ugandan atopics to alder
pollen (Alnus acuminata, plant family Betulaceae) caused serological cross
reactivity with Betula verrucosa-related allergens.
PMID- 26437182
TI - Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde
prefixed Brain of Rats with Serotonin Syndrome.
AB - 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) toxicity may cause region
specific changes in serotonergic mRNA expression due to acute serotonin (5
hydroxytryptamine; 5-HT) syndrome. This hypothesis can be tested using in situ
hybridization to detect the serotonin 5-HT2A receptor gene htr2a. In the past,
such procedures, utilizing radioactive riboprobe, were difficult because of the
complicated workflow that needs several days to perform and the added difficulty
that the technique required the use of fresh frozen tissues maintained in an
RNase-free environment. Recently, the development of short oligonucleotide probes
has simplified in situ hybridization procedures and allowed the use of
paraformaldehyde-prefixed brain sections, which are more widely available in
laboratories. Here, we describe a detailed protocol using non-radioactive
oligonucleotide probes on the prefixed brain tissues. Hybridization probes used
for this study include dapB (a bacterial gene coding for dihydrodipicolinate
reductase), ppiB (a housekeeping gene coding for peptidylprolyl isomerase B), and
htr2a (a serotonin gene coding for 5-HT2A receptors). This method is relatively
simply, cheap, reproducible and requires less than two days to complete.
PMID- 26437183
TI - Anharmonic Vibrational Analysis of the Infrared and Raman Gas-Phase Spectra of s
trans- and s-gauche-1,3-Butadiene.
AB - A quantum-mechanical (hybrid MP2/cc-pVTZ and CCSD(T)/cc-pVTZ) full quartic
potential energy surface (PES) in rectilinear normal coordinates and the second
order operator canonical Van Vleck perturbation theory (CVPT2) are employed to
predict the anharmonic vibrational spectra of s-trans- and s-gauche-butadiene
(BDE). These predictions are used to interpret their infrared and Raman
scattering spectra. New high-temperature Raman spectra in the gas phase are
presented in support of assignments for the gauche conformer. The CVPT2 solution
is based on a PES and electro-optical properties (EOP; dipole moment and
polarizability) expanded in Taylor series. Higher terms than those routinely
available from Gaussian09 software were calculated by numerical differentiation
of quadratic force fields and EOP using the MP2/cc-pVTZ model. The integer
coefficients of the polyad quantum numbers were derived for both conformers of
BDE. Replacement of harmonic frequencies by their counterparts from the
CCSD(T)/cc-pVTZ model significantly improved the agreement with experimental data
for s-trans-BDE (root-mean-square deviation ~ 5.5 cm(-1)). The accuracy in
predicting the rather well-studied spectrum of fundamentals of s-trans-BDE
assures good predictions of the spectrum of s-gauche-BDE. A nearly complete
assignment of fundamentals was obtained for the gauche conformer. Many
nonfundamental transitions of the BDE conformers were interpreted as well. The
predictions of multiple Fermi resonances in the complex CH-stretching region
correlate well with experiment. It is shown that solving a vibrational anharmonic
problem through a numerical-analytic implementation of CVPT2 is a straightforward
and computationally advantageous approach for medium-size molecules in comparison
with the standard second-order vibrational perturbation theory (VPT2) based on
analytic expressions.
PMID- 26437186
TI - Correction: Rhinos in the Parks: An Island-Wide Survey of the Last Wild
Population of the Sumatran Rhinoceros.
PMID- 26437184
TI - Statistical Analysis of Zebrafish Locomotor Response.
AB - Zebrafish larvae display rich locomotor behaviour upon external stimulation. The
movement can be simultaneously tracked from many larvae arranged in multi-well
plates. The resulting time-series locomotor data have been used to reveal new
insights into neurobiology and pharmacology. However, the data are of large
scale, and the corresponding locomotor behavior is affected by multiple factors.
These issues pose a statistical challenge for comparing larval activities. To
address this gap, this study has analyzed a visually-driven locomotor behaviour
named the visual motor response (VMR) by the Hotelling's T-squared test. This
test is congruent with comparing locomotor profiles from a time period. Different
wild-type (WT) strains were compared using the test, which shows that they
responded differently to light change at different developmental stages. The
performance of this test was evaluated by a power analysis, which shows that the
test was sensitive for detecting differences between experimental groups with
sample numbers that were commonly used in various studies. In addition, this
study investigated the effects of various factors that might affect the VMR by
multivariate analysis of variance (MANOVA). The results indicate that the larval
activity was generally affected by stage, light stimulus, their interaction, and
location in the plate. Nonetheless, different factors affected larval activity
differently over time, as indicated by a dynamical analysis of the activity at
each second. Intriguingly, this analysis also shows that biological and technical
repeats had negligible effect on larval activity. This finding is consistent with
that from the Hotelling's T-squared test, and suggests that experimental repeats
can be combined to enhance statistical power. Together, these investigations have
established a statistical framework for analyzing VMR data, a framework that
should be generally applicable to other locomotor data with similar structure.
PMID- 26437187
TI - Internship and Empathy: Variations Across Time and Specialties.
AB - OBJECTIVES: To assess whether any differences exist in Interpersonal Reactivity
Index (IRI) scores among postgraduate year 1 (PGY-1) residents across
specialties. METHODS: PGY-1 residents representing 11 specialties at our academic
institution were invited to take a Web-based IRI survey at three time points. The
specialties were condensed into several binary groups for analysis: internal
medicine (IM) versus non-IM; primary care (IM, family medicine) versus nonprimary
care; emergency medicine (EM, including the combined IM/EM) versus non-EM;
surgical specialties (general surgery, obstetrics and gynecology, otolaryngology,
orthopedics, urology) versus nonsurgical specialties (EM, family medicine, IM,
neurology, pathology, and psychiatry); men versus women; and age groups. A
repeated-measures generalized-estimating equations approach was taken to analyze
the effect of specialty and time on each of the four IRI subscales. RESULTS: Of
94 PGY-1 residents invited to participate at each time point, 74 (77.1%)
completed the survey at least once. Response rates at each time point were
similar (mean 47.9%). When comparing the IM (n=35) and non-IM (n=39) groups, the
perspective-taking subscale was found to be significantly lower in the non-IM
group (P=0.006). Among male (n=46) versus female residents (n=26), the personal
distress subscale was significantly different overall (P=0.041) but not among
time points. No other significant differences were found between groups. The
conglomerate subscale scores throughout the year did not show a dramatic change.
CONCLUSIONS: Our study of IRI subscales in PGY-1 residents showed no major
difference among specialties across 1 year except for IM residents, who scored
significantly higher (more favorably) in the perspective-taking subscale.
Contrary to previous studies, we did not observe a substantial decline in the
empathic concern subscale IM residents over their first year.
PMID- 26437188
TI - Analysis of a Guideline-Derived Resident Educational Program on Inpatient
Glycemic Control.
AB - OBJECTIVES: To determine the effects of a guideline-derived resident educational
program on inpatient glycemic control and length of hospital stay (LOS). METHODS:
We compared the following variables before and after resident education:
percentage of patients on basal-plus-bolus regimens, mean fingerstick glucose
(FSG), LOS, and rates of hypoglycemia (FSG<70 mg/dL) and severe hypoglycemia
(FSG<40 mg/dL). A two-tailed t test was used for all continuous data and P<0.05
was considered statistically significant. RESULTS: After education, more patients
(23% vs 8%; P=0.024) were placed on basal-plus-bolus regimens. We observed a
decrease in mean FSG (158.7 mg/dL vs 165.1 mg/dL; P=0.028) and LOS (5.03 days vs
6.98 days; P=0.042). Rates of hypoglycemia (4.6% vs 1.5%; P<0.001) and severe
hypoglycemia (0.71% vs 0.24%; P=0.089) increased. CONCLUSIONS: Our resident
educational program significantly increased the number of patients receiving
guideline-based inpatient insulin therapy and was associated with a reduction in
mean FSG and LOS. Rates of hypoglycemia showed a statistically significant
increase, whereas rates of severe hypoglycemia did not. Larger multicenter
studies with adjustment for potential confounders are needed to further assess
the impact of educational interventions on inpatient glycemic control.
PMID- 26437189
TI - How Does Legalization of Physician-Assisted Suicide Affect Rates of Suicide?
AB - OBJECTIVES: Several US states have legalized or decriminalized physician-assisted
suicide (PAS) while others are considering permitting PAS. Although it has been
suggested that legalization could lead to a reduction in total suicides and to a
delay in those suicides that do occur, to date no research has tested whether
these effects can be identified in practice. The aim of this study was to fill
this gap by examining the association between the legalization of PAS and state
level suicide rates in the United States between 1990 and 2013. METHODS: We used
regression analysis to test the change in rates of nonassisted suicides and total
suicides (including assisted suicides) before and after the legalization of PAS.
RESULTS: Controlling for various socioeconomic factors, unobservable state and
year effects, and state-specific linear trends, we found that legalizing PAS was
associated with a 6.3% (95% confidence interval 2.70%-9.9%) increase in total
suicides (including assisted suicides). This effect was larger in the individuals
older than 65 years (14.5%, CI 6.4%-22.7%). Introduction of PAS was neither
associated with a reduction in nonassisted suicide rates nor with an increase in
the mean age of nonassisted suicide. CONCLUSIONS: Legalizing PAS has been
associated with an increased rate of total suicides relative to other states and
no decrease in nonassisted suicides. This suggests either that PAS does not
inhibit (nor acts as an alternative to) nonassisted suicide, or that it acts in
this way in some individuals but is associated with an increased inclination to
suicide in other individuals.
PMID- 26437190
TI - Social Contagion Effects of Physician-Assisted Suicide: Commentary on "How Does
Legalization of Physician-Assisted Suicide Affect Rates of Suicide?".
PMID- 26437191
TI - Academic Health Centers and Diversity "Readiness".
PMID- 26437192
TI - Commentary on "Academic Health Centers and Diversity 'Readiness'".
PMID- 26437193
TI - Chronic Pain Visits and Academic Medicine for Underrepresented Minorities: The
Surprising Parallel.
PMID- 26437194
TI - Waiting in the Accident and Emergency Department: Exploring Problematic
Experiences.
AB - OBJECTIVES: To investigate the relation between perceived waiting times and
patients' overall ratings of accident and emergency departments (A&Es) and to
explore which patients view waiting times as problematic. METHODS: A cross
sectional survey was held in 21 A&Es in the Netherlands. From each A&E, a random
sample of patients was investigated. Patients younger than 18 years and patients
who had arrived by ambulance were excluded. Respondents' perceived waiting times
and overall quality ratings of their A&E visit were collected and correlated.
Respondents were divided into a "no problem" or "problem" group on the basis of
the perceived waiting time before treatment. Logistic regression analyses were
performed to explore factors potentially related to problematic waiting
experiences, such as the amount of information received while waiting and
perceived pain and acuity. RESULTS: The study included 3483 patients. Longer
perceived waiting time was associated with a decrease in overall rating and
increased reports of problematic experiences. Multivariate analysis showed that
problematic waiting experiences were significantly associated with perceived pain
(odds ratio [OR] 1.1), higher perceived acuity (emergency/urgent/nonurgent ORs:
2.7/2.2/1.0) and limited information before treatment. The OR for patients who
did not receive any information about what to expect during a visit to the A&E
versus patients who were completely informed was 3.3. For uninformed versus
completely informed patients, the OR for information about how quickly patients
needed to be helped with their health problem was 3.4. CONCLUSIONS: Providing
information before treatment, controlling the perception of pain, and managing
perceived acuity not only reduced problematic experiences concerning perceived
waiting time but also improved experienced quality of care.
PMID- 26437195
TI - Differentiating Bipolar Disorder from Attention-Deficit/Hyperactivity Disorder in
Children.
PMID- 26437196
TI - Virtual and Peer Reviews of Grant Applications at the Agency for Healthcare
Research and Quality.
AB - OBJECTIVES: This study documents the first six unplanned virtual review (VR)
sessions conducted during the 2012 hurricane season at the Agency for Healthcare
Research and Quality and their effects on review outcomes. It also compares these
VR sessions with five face-to-face (FF) sessions. METHODS: In the first part of
this study, six VR sessions are analyzed in terms of feasibility,
reproducibility, and reviewers' responses to a questionnaire about VR. In the
second part, the VR sessions are compared with five other FF meetings in terms of
costs and duration per discussed application. RESULTS: Despite their technical
novelty, all of the VR sessions have been successfully conducted to the
satisfaction of reviewers and agency organizers. Special emphasis panel reviewers
are more receptive to the new technology than study section reviewers: 75% versus
42%, respectively (P<0.05). Although the duration per discussed application is
comparable to FF, the cost per reviewer is much lower for VR sessions than FF
sessions. CONCLUSIONS: VR has successfully been used in six review sessions with
a maximum of 34 discussed applications per session, special emphasis panel
reviewers are more receptive to VR than SS reviewers, VR is a duplicable and low
cost method of review, and practitioners and scientists are urged to serve as
reviewers because doing so may assist them in receiving funding.
PMID- 26437197
TI - Achieving Excellence in Pharmaceutical Care.
PMID- 26437198
TI - SMJ Response.
PMID- 26437199
TI - An Investigation of the Variety and Complexity of Statistical Methods Used in
Current Internal Medicine Literature.
AB - OBJECTIVES: Accreditation Council for Graduate Medical Education guidelines
require internal medicine residents to develop skills in the interpretation of
medical literature and to understand the principles of research. A necessary
component is the ability to understand the statistical methods used and their
results, material that is not an in-depth focus of most medical school curricula
and residency programs. Given the breadth and depth of the current medical
literature and an increasing emphasis on complex, sophisticated statistical
analyses, the statistical foundation and education necessary for residents are
uncertain. METHODS: We reviewed the statistical methods and terms used in 49
articles discussed at the journal club in the Department of Internal Medicine
residency program at Texas Tech University between January 1, 2013 and June 30,
2013. We collected information on the study type and on the statistical methods
used for summarizing and comparing samples, determining the relations between
independent variables and dependent variables, and estimating models. We then
identified the typical statistics education level at which each term or method is
learned. RESULTS: A total of 14 articles came from the Journal of the American
Medical Association Internal Medicine, 11 from the New England Journal of
Medicine, 6 from the Annals of Internal Medicine, 5 from the Journal of the
American Medical Association, and 13 from other journals. Twenty reported
randomized controlled trials. Summary statistics included mean values (39
articles), category counts (38), and medians (28). Group comparisons were based
on t tests (14 articles), chi2 tests (21), and nonparametric ranking tests (10).
The relations between dependent and independent variables were analyzed with
simple regression (6 articles), multivariate regression (11), and logistic
regression (8). Nine studies reported odds ratios with 95% confidence intervals,
and seven analyzed test performance using sensitivity and specificity
calculations. These papers used 128 statistical terms and context-defined
concepts, including some from data analysis (56), epidemiology-biostatistics
(31), modeling (24), data collection (12), and meta-analysis (5). Ten different
software programs were used in these articles. Based on usual undergraduate and
graduate statistics curricula, 64.3% of the concepts and methods used in these
papers required at least a master's degree-level statistics education.
CONCLUSIONS: The interpretation of the current medical literature can require an
extensive background in statistical methods at an education level exceeding the
material and resources provided to most medical students and residents. Given the
complexity and time pressure of medical education, these deficiencies will be
hard to correct, but this project can serve as a basis for developing a
curriculum in study design and statistical methods needed by physicians-in
training.
PMID- 26437200
TI - Commentary on "An Investigation of the Variety and Complexity of Statistical
Methods Used in Current Internal Medicine Literature".
PMID- 26437201
TI - Effect of Body Weight on Dose of Vitamin K Antagonists.
AB - OBJECTIVES: Numerous factors are well documented to affect the response to
vitamin K antagonists (VKA), including dietary vitamin K, other drugs, age,
pharmacogenetics, and disease states. Body weight is perhaps not as well known as
a variable affecting VKA dose. Our aim was to review the literature regarding
body weight and VKA dose requirements. METHODS: We reviewed the English-language
literature via PubMed and Scopus using the search terms VKA, warfarin,
acenocoumarol, phenprocoumon, fluindione, AND body weight. RESULTS: Among 32
studies conducted since the widespread use of the international normalized ratio,
29 found a correlation with body weight or body surface area and VKA dose
requirement. Warfarin was evaluated in 27 studies and acenocoumarol,
phenprocoumon, or fluindione were assessed in 5 investigations. CONCLUSIONS:
Because of varying study methodologies, further study is warranted. Based on
current evidence, clinicians should include body weight, along with other
established variables when dosing VKA. Most important, obese and morbidly obese
patients may require a 30% to 50% increase with the initial dosing of VKA.
PMID- 26437202
TI - Global Drug Safety Insights From Taiwan.
PMID- 26437203
TI - Azole Resistance in Dermatophytes: Prevalence and Mechanism of Action.
AB - Azole antifungal agents (eg, fluconazole and itraconazole) have been widely used
to treat superficial fungal infections caused by dermatophytes and, unlike the
allylamines (such as terbinafine and naftifine), have been associated with
resistance development. Although many published manuscripts describe resistance
to azoles among yeast and molds, reports describing resistance of dermatophytes
are starting to appear. In this review, I discuss the mode of action of azole
antifungals and mechanisms underlying their resistance compared with the
allylamine class of compounds. Data from published and original studies were
compared and summarized, and their clinical implications are discussed. In
contrast to the cidal allylamines, static drugs such as azoles permit the
occurrence of mutations in enzymes involved in ergosterol biosynthesis, and the
ergosterol precursors accumulating as a consequence of azole action are not
toxic. Azole antifungals, unlike allylamines, potentiate resistance development
in dermatophytes.
PMID- 26437204
TI - Erratum: Stock W, Johnson JL, Stone RM, Kolitz JE, Powell BL, Wetzler M,
Westervelt P, Marcucci G, DeAngelo DJ, Vardiman JW, McDonnell D, Mrozek K,
Bloomfield CD and Larson R A. Dose intensification of daunorubicin and cytarabine
during treatment of adult acute lymphoblastic leukemia. Cancer. 2013;119:90-8.
PMID- 26437206
TI - What is your diagnosis? Urine crystals in a dog.
PMID- 26437208
TI - Tracking the Effect of Adatom Electronegativity on Systematically Modified
AlGaN/GaN Schottky Interfaces.
AB - The influence of surface modifications on the Schottky barrier height for gallium
nitride semiconductor devices is frequently underestimated or neglected in
investigations thereof. We show that a strong dependency of Schottky barrier
heights for nickel/aluminum-gallium nitride (0001) contacts on the surface
terminations exists: a linear correlation of increasing barrier height with
increasing electronegativity of superficial adatoms is observed. The negatively
charged adatoms compete with the present nitrogen over the available gallium (or
aluminum) orbital to form an electrically improved surface termination. The
resulting modification of the surface dipoles and hence polarization of the
surface termination causes observed band bending. Our findings suggest that the
greatest Schottky barrier heights are achieved by increasing the concentration of
the most polarized fluorine-gallium (-aluminum) bonds at the surface. An increase
in barrier height from 0.7 to 1.1 eV after a 15% fluorine termination is obtained
with ideality factors of 1.10 +/- 0.05. The presence of surface dipoles that are
changing the surface energy is proven by the sessile drop method as the
electronegativity difference and polarization influences the contact angle. The
extracted decrease in the Lifshitz-van-der-Waals component from 48.8 to 40.4
mJ/m(2) with increasing electronegativity and concentration of surface adatoms
confirms the presence of increasing surface dipoles: as the polarizability of
equally charged anions decreases with increasing electronegativity, the
diiodomethane contact angles increase significantly from 14 degrees up to 39
degrees after the 15% fluorine termination. Therefore, a linear correlation
between increasing anion electronegativity of the (Al)GaN termination and total
surface energy within a 95% confidence interval is obtained. Furthermore, our
results reveal a generally strong Lewis basicity of (Al)GaN surfaces explaining
the high chemical inertness of the surfaces.
PMID- 26437207
TI - Management of periorbital basal cell carcinoma with orbital invasion.
AB - Basal cell carcinoma (BCC) is the most common eyelid malignancy; however, orbital
invasion by periocular BCC is rare, and management remains challenging.
Established risk factors for orbital invasion by BCC include male gender,
advanced age, medial canthal location, previous recurrences, large tumor size,
aggressive histologic subtype and perineural invasion. Management requires a
multidisciplinary approach with orbital exenteration remaining the treatment of
choice. Globe-sparing treatment may be appropriate in selected patients and
radiotherapy and chemotherapy are often used as adjuvant therapies for advanced
or inoperable cases, although the evidence remains limited. We aim to summarize
the presentation and treatment of BCC with orbital invasion to better guide the
management of this complex condition.
PMID- 26437209
TI - No association between schizophrenia susceptibility variants and macroscopic
structural brain volume variation in healthy subjects.
AB - Previous studies have suggested that genetic variants for schizophrenia
susceptibility might contribute to structural brain volume variations in
schizophrenia patients, including total brain volume, hippocampal volume, and
amygdalar volume. However, whether these schizophrenia susceptibility variants
are associated with macroscopic structural brain volume (i.e., intracranial
volume, total brain volume, and hippocampal volume) in healthy subjects is still
unclear. In this study, we investigated the associations between 47 schizophrenia
susceptibility variants (from 25 well-characterized schizophrenia susceptibility
genes) and cranial volume variation in a healthy Chinese sample (N = 1,013). We
also extracted the association between these 47 schizophrenia risk variants and
the macroscopic structural brain volume (intracranial volume, total brain volume
and hippocampal volume) in a large healthy sample of European ancestry (ENIGMA
sample, N = 5,775). We identified several single-nucleotide polymorphisms (SNPs)
nominally associated with intracranial volume, total brain volume, and
hippocampal volume at P < 0.05 (uncorrected). However, after Bonferroni
corrections for multiple testing, no SNP showed significant association. Hence,
our results do not support previous observations that schizophrenia
susceptibility variants are associated with brain structure (e.g., hippocampal
volume) in healthy individuals, and indicate that single schizophrenia risk
variant may not contribute significantly to macroscopic brain structure (e.g.,
intracranial volume or hippocampal volume) variation in healthy subjects.
PMID- 26437210
TI - miRNA-mediated auxin signalling repression during Vat-mediated aphid resistance
in Cucumis melo.
AB - Resistance to Aphis gossypii in melon is attributed to the presence of the single
dominant R gene virus aphid transmission (Vat), which is biologically expressed
as antibiosis, antixenosis and tolerance. However, the mechanism of resistance is
poorly understood at the molecular level. Aphid-induced transcriptional changes,
including differentially expressed miRNA profiles that correspond to resistance
interaction have been reported in melon. The potential regulatory roles of miRNAs
in Vat-mediated aphid resistance were further revealed by identifying the
specific miRNA degradation targets. A total of 70 miRNA:target pairs, including
28 novel miRNA:target pairs, for the differentially expressed miRNAs were
identified: 11 were associated with phytohormone regulation, including six miRNAs
that potentially regulate auxin interactions. A model for a redundant regulatory
system of miRNA-mediated auxin insensitivity is proposed that incorporates auxin
perception, auxin modification and auxin-regulated transcription. Chemically
inhibiting the transport inhibitor response-1 (TIR-1) auxin receptor in
susceptible melon tissues provides in vivo support for the model of auxin
mediated impacts on A. gossypii resistance.
PMID- 26437212
TI - Apoptosis- and cell cycle-related genes methylation profile in myeloproliferative
neoplasms.
PMID- 26437211
TI - Biochemical Characterization of Human Anti-Hepatitis B Monoclonal Antibody
Produced in the Microalgae Phaeodactylum tricornutum.
AB - Monoclonal antibodies (mAbs) represent actually the major class of
biopharmaceuticals. They are produced recombinantly using living cells as
biofactories. Among the different expression systems currently available,
microalgae represent an emerging alternative which displays several
biotechnological advantages. Indeed, microalgae are classified as generally
recognized as safe organisms and can be grown easily in bioreactors with high
growth rates similarly to CHO cells. Moreover, microalgae exhibit a phototrophic
lifestyle involving low production costs as protein expression is fueled by
photosynthesis. However, questions remain to be solved before any industrial
production of algae-made biopharmaceuticals. Among them, protein heterogeneity as
well as protein post-translational modifications need to be evaluated.
Especially, N-glycosylation acquired by the secreted recombinant proteins is of
major concern since most of the biopharmaceuticals including mAbs are N
glycosylated and it is well recognized that glycosylation represent one of their
critical quality attribute. In this paper, we assess the quality of the first
recombinant algae-made mAbs produced in the diatom, Phaeodactylum tricornutum. We
are focusing on the characterization of their C- and N-terminal extremities,
their signal peptide cleavage and their post-translational modifications
including N-glycosylation macro- and microheterogeneity. This study brings
understanding on diatom cellular biology, especially secretion and intracellular
trafficking of proteins. Overall, it reinforces the positioning of P. tricornutum
as an emerging host for the production of biopharmaceuticals and prove that P.
tricornutum is suitable for producing recombinant proteins bearing high mannose
type N-glycans.
PMID- 26437213
TI - PATIENTS' PERCEPTION ON CLINICAL OUTCOME AND QUALITY OF LIFE AFTER A DIAGNOSIS OF
CUSHING SYNDROME.
AB - OBJECTIVE: Excess cortisol production (Cushing syndrome, CS) is a chronic disease
affecting many organ systems and impacting quality of life (QoL). This study
analyzed factors associated with self-reported QoL, including aspects related to
the diagnosis and treatment modalities of CS. METHODS: In collaboration with the
Cushing's Support and Research Foundation (CSRF), surveys using a validated QoL
instrument were sent to CSRF members. Data were analyzed for associations between
QoL and demographic, treatment, and disease factors. RESULTS: A total of 269
patients completed the survey. Respondents were 89.9% female, and the mean age
was 48 years (SD 12, range 16-76). Respondents visited a median of 4 physicians
(range 1-40) prior to the diagnosis of CS, with a median of 5 years (mean 7, SD
5, range 1-30) to obtain a diagnosis, showing a statistically significant
negative correlation (P<.001). In one-quarter of cases, someone other than a
physician suggested the diagnosis. Multiple regression analysis demonstrated that
remission status, time to diagnosis, radiation therapy, and hypopituitarism were
significant predictors of QoL. There was no association between QoL and patient's
sex, age, replacement steroid use, having follow-up with an endocrinologist, or
surgical approach. CONCLUSION: This is one of the largest QoL studies of CS
patients and provides information for treatment and education goals. It is
notable that early diagnosis and treatment was the major predictor of better QoL
after achieving remission from disease, highlighting the need for awareness about
the disorder. Patients in remission had better QoL, emphasizing the importance of
disease control.
PMID- 26437214
TI - LIMITATIONS OF CURRENT APPROACHES FOR THE TREATMENT OF ACROMEGALY.
AB - OBJECTIVE: Acromegaly is a rare disease characterized by hypersecretion of growth
hormone (GH), typically from a benign pituitary somatotroph adenoma, that leads
to subsequent hypersecretion of insulin-like growth factor 1 (IGF-1). Patients
with acromegaly have an increased risk of mortality and progressive worsening of
comorbidities. Surgery, medical therapy, and radiotherapy are currently available
treatment approaches for patients with acromegaly, with overall therapeutic goals
of lowering GH levels and achieving normal IGF-1 levels, reducing tumor size,
improving comorbidities, and minimizing mortality risk. Although surgery can lead
to biochemical remission in some patients with acromegaly, many patients will
continue to have uncontrolled disease and require additional treatment. METHODS:
We reviewed recently published reports and present a summary of the safety and
efficacy of current treatment modalities for patients with acromegaly. RESULTS: A
substantial proportion of patients who receive medical therapy or radiotherapy
will have persistently elevated GH and/or IGF-1. Because of the serious health
consequences of continued elevation of GH and IGF-1, there is a need to improve
therapeutic approaches to optimize biochemical control, particularly in high-need
patient populations for whom current treatment options provide limited benefit.
CONCLUSION: This review discusses current treatment options for patients with
acromegaly, limitations associated with each treatment approach, and areas within
the current treatment algorithm, as well as patient populations for which
improved therapeutic options are needed. Novel agents in development were also
highlighted, which have the potential to improve management of patients with
uncontrolled or persistent acromegaly.
PMID- 26437215
TI - INCREASING PREVALENCE OF ADDISON DISEASE: RESULTS FROM A NATIONWIDE STUDY.
AB - OBJECTIVE: Primary adrenal insufficiency is a life-threatening endocrine disease
unless properly treated. However, few studies on the prevalence, concomitances of
the disease, and prescribing of drugs have been published. The goal of the study
was to establish the prevalence of primary adrenal insufficiency in Iceland and
additionally, to study the most common concomitant diseases in patients with
primary adrenal insufficiency, as well as the mode of glucocorticoid replacement
therapies. METHODS: To achieve this, the medical records of all patients in
Iceland who had received the International Classification of Diseases and Related
Health Problems, 10th Revision, diagnosis code E27, were evaluated for true
primary adrenal insufficiency. Additionally, these records were evaluated for
concomitant diseases, as well as the mode of glucocorticoid replacement therapy.
The study covered the whole population of Iceland over 18 years of age. It was
thus a nationwide study. The records were retrieved from large hospitals and
clinics and every practicing specialist in endocrinology. RESULTS: Primary
adrenal insufficiency was found in 53 individuals, 26 women and 27 men, yielding
a prevalence of 22.1 per 100,000 population. Hypothyroidism was by far the most
common concomitant disease. Most patients had their glucocorticoid deficiency
replaced with short-acting glucocorticoids. CONCLUSION: The prevalence of primary
adrenal insufficiency in Iceland is higher than in earlier reports, with
comorbidities being in line with recent studies. Treatment is according to the
latest protocols.
PMID- 26437216
TI - OUTCOME OF IMPLEMENTATION OF A MULTIDISCIPLINARY TEAM APPROACH TO THE CARE OF
PATIENTS AFTER TRANSSPHENOIDAL SURGERY.
AB - OBJECTIVE: Transsphenoidal surgery (TS) for sellar lesions is an established and
safe procedure, but complications can occur, particularly involving the
neuroendocrine system. We hypothesized that postoperative care of TS patients
would be optimized when performed by a coordinated team including a pituitary
neurosurgeon, endocrinologists, and a specialty nurse. METHODS: We implemented a
formalized, multidisciplinary team approach and standardized postoperative
protocols for the care of adult patients undergoing TS by a single surgeon
(J.N.B.) at our institution beginning in July 2009. We retrospectively compared
the outcomes of 214 consecutive TS-treated cases: 113 cases prior to and 101
following the initiation of the team approach and protocol implementation.
Outcomes assessed included the incidence of neurosurgical and endocrine
complications, length of stay (LOS), and rates of hospital readmission and
unscheduled clinical visits. RESULTS: The median LOS decreased from 3 days
preteam to 2 days postteam (P<.01). Discharge occurred on postoperative day 2 in
46% of the preteam group patients compared to 69% of the postteam group (P<.01).
Rates of early postoperative diabetes insipidus (DI) and readmissions within 30
days for syndrome of inappropriate antidiuretic hormone (SIADH) or other
complications did not differ between groups. CONCLUSION: Implementation of a
multidisciplinary team approach was associated with a reduction of LOS. Despite
earlier discharge, postoperative outcomes were not compromised. The
endocrinologist is central to the success of this team approach, which could be
successfully applied to care of patients undergoing TS, as well as other types of
endocrine surgery at other centers.
PMID- 26437217
TI - HISTORICAL RESPONSE RATES OF SOMATOSTATIN ANALOGUES IN THE TREATMENT OF
ACROMEGALY: A SYSTEMATIC REVIEW.
AB - OBJECTIVE: In a completed phase III study (C2305, Clinicaltrials.gov identifier:
NCT00600886), the reported rate of biochemical control with octreotide long
acting release (LAR) was lower than rates historically reported in patients
pretreated and/or selected for response with somatostatin analogue (SSA) therapy.
To assess whether lower efficacy rates of octreotide LAR in C2305 were influenced
by study design, a systematic review of the literature was performed to evaluate
response rates in previously published studies in acromegaly with similar design
characteristics. METHODS: PubMed was used to search for English-language clinical
studies of acromegaly published through May 2014. Prospective studies of
medically naive patients (>=20) treated with SSAs for <=12 months that reported
efficacy rates using composite endpoint measures (growth hormone [GH] and insulin
like growth factor 1 [IGF-1]) were included. Two separate authors independently
screened abstracts and full-length articles of each study to determine
eligibility. All authors met to review and reach consensus when primary reviewers
disagreed on the inclusion or exclusion of specific studies. RESULTS: A total of
9 studies (N = 354 patients) were identified, with reported mean efficacy rates
of 31% (range, 20-54%). Of note, reported mean efficacy rates were lower in
studies enrolling patients naive to any form of treatment (surgery, medical,
and/or radiation) than in studies that enrolled only medically naive patients. A
limitation of this analysis was that inclusion criteria restricted the number of
studies analyzed. CONCLUSION: Interpretation of biochemical response rates with
SSAs is critically dependent on the context of the study and should be evaluated
across clinical trials with similar study design characteristics.
PMID- 26437218
TI - IS IT TIME TO EMANCIPATE PLASMA CORTISOL?
PMID- 26437219
TI - SELECTION OF ENDOCRINOLOGY SUBSPECIALTY TRAINEES: WHICH APPLICANT CHARACTERISTICS
ARE ASSOCIATED WITH PERFORMANCE DURING FELLOWSHIP TRAINING?
AB - OBJECTIVE: To determine which residency characteristics are associated with
performance during endocrinology fellowship training as measured by competency
based faculty evaluation scores and faculty global ratings of trainee
performance. METHODS: We performed a retrospective review of interview
applications from endocrinology fellows who graduated from a single academic
institution between 2006 and 2013. Performance measures included competency-based
faculty evaluation scores and faculty global ratings. The association between
applicant characteristics and measures of performance during fellowship was
examined by linear regression. RESULTS: The presence of a laudatory comparative
statement in the residency program director's letter of recommendation (LoR) or
experience as a chief resident was significantly associated with competency-based
faculty evaluation scores (beta = 0.22, P = .001; and beta = 0.24, P = .009,
respectively) and faculty global ratings (beta = 0.85, P = .006; and beta = 0.96,
P = .015, respectively). CONCLUSION: The presence of a laudatory comparative
statement in the residency program director's LoR or experience as a chief
resident were significantly associated with overall performance during
subspecialty fellowship training. Future studies are needed in other cohorts to
determine the broader implications of these findings in the application and
selection process.
PMID- 26437220
TI - LEVOTHYROXINE REPLACEMENT IN OBESE HYPOTHYROID FEMALES AFTER TOTAL THYROIDECTOMY.
AB - OBJECTIVE: Levothyroxine (LT4) replacement in hypothyroid obese patients is
poorly understood. We assessed whether the LT4 regimen required to achieve
euthyroidism differs between nonobese and obese hypothyroid females. METHODS: We
retrospectively identified nonobese and obese females who received LT4 starting
with a standard dose of 1.6 MUg/kg after total thyroidectomy for preoperative
diagnosis of benign goiter. We examined the association between LT4 dosage
required to achieve euthyroid state (thyroid-stimulating hormone [TSH] 0.4-2.5
mIU/L) and patient characteristics using linear regression models with and
without adjustment for age, ethnicity, medication use, and postoperative
hypoparathyroidism. RESULTS: We identified 32 females (15 nonobese/17 obese) who
achieved euthyroid state. Obese patients weighed more (104.1 +/- 22.5 vs. 64.9 +/
10.0 kg, P<.0001) and required a higher final LT4 than nonobese (146 +/- 38 vs.
102 +/- 12 MUg, P = .0002) but LT4 requirements per kg total body weight (TBW)
were similar (1.60 +/- 0.29 vs. 1.42 +/- 0.38 MUg/kg, P = .15). LT4 dose per kg
ideal body weight (IBW) was higher in obese than in nonobese females (2.62 +/-
0.67 vs. 1.88 +/- 0.28 MUg/kg, P = .0004) and this difference persisted after
adjustments (P<.05). During LT4 titration, 47% and 20% of obese and nonobese
patients had subnormal TSH episodes, respectively (P = .11). After taking LT4
compliance, malabsorption, and competing medication use into consideration, we
found marked LT4 dose variability in obese patients. Patients who needed a mean
daily LT4 dose <=150 mg (124 +/- 16 MUg/day) compared with >150 MUg (198 +/- 4
MUg/day) demonstrated lower LT4 per TBW (1.25 +/- 0.18 vs. 1.84 +/- 0.43 MUg/kg,
P = .03) and IBW (2.28 +/- 0.47 vs. 3.44 +/- 0.18 MUg/kg, P<.0001), respectively.
CONCLUSION: The standard approach to LT4 replacement in obese and nonobese
females after thyroidectomy is imprecise. Mean daily LT4 doses in obese and
nonobese patients were similar if expressed per kg TBW, though there was
variability in the final LT4 among obese patients. We suggest initiating LT4 at a
dose lower than that routinely recommended in obese females.
PMID- 26437222
TI - Cetuximab promotes epithelial to mesenchymal transition and cancer associated
fibroblasts in patients with head and neck cancer.
AB - PURPOSE: To investigate if cetuximab induces epithelial to mesenchymal transition
(EMT) and activation of cancer associated fibroblast (CAF) in the tumors of
patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS:
Cetuximab was administered for two weeks prior to surgery to 20 treatment-naive
patients. Five untreated patients were included as controls. Tumor biopsies were
performed at baseline and before surgery. Gene expression profiles and
quantitative real-time PCR (qRT-PCR) analysis of the pre-and post-treatment
biopsies were compared. To further investigate EMT and CAF, correlations between
previously described EMT and CAF markers and our microarray data set were
calculated. RESULTS: Gene expression profile analyses and qRT-PCR showed that
some of the genes modified by cetuximab were related to CAFs and EMT (ZNF521,
CXCL12, ASPN, OLFML3, OLFM1, TWIST1, LEF1, ZEB1, FAP). We identified 2 patient
clusters with different EMT and CAF characteristics. Whereas one cluster showed
clear upregulation of expression of genes implicated in CAF and EMT including
markers of embryologic pathways like NOTCH and Wnt, the other did not.
CONCLUSIONS: Even if EMT and CAFs are implicated in cetuximab resistance in pre
clinical models, we demonstrate for the first time that these molecular processes
may occur clinically early on.
PMID- 26437221
TI - Induction of KIAA1199/CEMIP is associated with colon cancer phenotype and poor
patient survival.
AB - Genes induced in colon cancer provide novel candidate biomarkers of tumor
phenotype and aggressiveness. We originally identified KIAA1199 (now officially
called CEMIP) as a transcript highly induced in colon cancer: initially
designating the transcript as Colon Cancer Secreted Protein 1. We molecularly
characterized CEMIP expression both at the mRNA and protein level and found it is
a secreted protein induced an average of 54-fold in colon cancer. Knockout of
CEMIPreduced the ability of human colon cancer cells to form xenograft tumors in
athymic mice. Tumors that did grow had increased deposition of hyaluronan,
linking CEMIP participation in hyaluronan degradation to the modulation of tumor
phenotype. We find CEMIP mRNA overexpression correlates with poorer patient
survival. In stage III only (n = 31) or in combined stage II plus stage III colon
cancer cases (n = 73), 5-year overall survival was significantly better (p =
0.004 and p = 0.0003, respectively) among patients with low CEMIP expressing
tumors than those with high CEMIP expressing tumors. These results demonstrate
that CEMIP directly facilitates colon tumor growth, and high CEMIP expression
correlates with poor outcome in stage III and in stages II+III combined cohorts.
We present CEMIP as a candidate prognostic marker for colon cancer and a
potential therapeutic target.
PMID- 26437223
TI - miR-135b suppresses tumorigenesis in glioblastoma stem-like cells impairing
proliferation, migration and self-renewal.
AB - Glioblastoma multiforme (GBM) is the most common and fatal malignant adult
primary brain tumor. Currently, the overall prognosis for GBM patients remains
poor despite advances in neurosurgery and adjuvant treatments. MicroRNAs (miRNAs)
contribute to the pathogenesis of various types of tumor, including GBM. In this
study we analyzed the expression of a panel of miRNAs, which are known to be
differentially expressed by the brain and GBM tumor, in a collection of patient
derived GBM stem-like cells (GSCs). Notably, the average expression level of miR
135b, was the most downregulated compared to its normal counterpart, suggesting a
potential role as anti-oncogene.Restoration of miR-135b in GSCs significantly
decreased proliferation, migration and clonogenic abilities. More importantly,
miR-135b restoration was able to significantly reduce brain infiltration in mouse
models of GBM obtained by intracerebral injection of GSC lines. We identified
ADAM12 and confirmed SMAD5 and GSK3beta as miR-135b targets and potential
mediators of its effects. The whole transcriptome analysis ascertained that the
expression of miR-135b downmodulated additional genes driving key pathways in GBM
survival and infiltration capabilities.Our results identify a critical role of
miR-135b in the regulation of GBM development, suggesting that miR-135b might act
as a tumor-suppressor factor and thus providing a potential candidate for the
treatment of GBM patients.
PMID- 26437224
TI - Serine protease inhibitor Kazal type 1 (SPINK1) drives proliferation and anoikis
resistance in a subset of ovarian cancers.
AB - Ovarian cancer represents the most lethal tumor type among malignancies of the
female reproductive system. Overall survival rates remain low. In this study, we
identify the serine protease inhibitor Kazal type 1 (SPINK1) as a potential
therapeutic target for a subset of ovarian cancers. We show that SPINK1 drives
ovarian cancer cell proliferation through activation of epidermal growth factor
receptor (EGFR) signaling, and that SPINK1 promotes resistance to anoikis through
a distinct mechanism involving protease inhibition. In analyses of ovarian tumor
specimens from a Mayo Clinic cohort of 490 patients, we further find that SPINK1
immunostaining represents an independent prognostic factor for poor survival,
with the strongest association in patients with nonserous histological tumor
subtypes (endometrioid, clear cell, and mucinous). This study provides novel
insight into the fundamental processes underlying ovarian cancer progression, and
also suggests new avenues for development of molecularly targeted therapies.
PMID- 26437225
TI - Chemogenetic profiling identifies RAD17 as synthetically lethal with checkpoint
kinase inhibition.
AB - Chemical inhibitors of the checkpoint kinases have shown promise in the treatment
of cancer, yet their clinical utility may be limited by a lack of molecular
biomarkers to identify specific patients most likely to respond to therapy. To
this end, we screened 112 known tumor suppressor genes for synthetic lethal
interactions with inhibitors of the CHEK1 and CHEK2 checkpoint kinases. We
identified eight interactions, including the Replication Factor C (RFC)-related
protein RAD17. Clonogenic assays in RAD17 knockdown cell lines identified a
substantial shift in sensitivity to checkpoint kinase inhibition (3.5-fold) as
compared to RAD17 wild-type. Additional evidence for this interaction was found
in a large-scale functional shRNA screen of over 100 genotyped cancer cell lines,
in which CHEK1/2 mutant cell lines were unexpectedly sensitive to RAD17
knockdown. This interaction was widely conserved, as we found that RAD17
interacts strongly with checkpoint kinases in the budding yeast Saccharomyces
cerevisiae. In the setting of RAD17 knockdown, CHEK1/2 inhibition was found to be
synergistic with inhibition of WEE1, another pharmacologically relevant
checkpoint kinase. Accumulation of the DNA damage marker gammaH2AX following
chemical inhibition or transient knockdown of CHEK1, CHEK2 or WEE1 was magnified
by knockdown of RAD17. Taken together, our data suggest that CHEK1 or WEE1
inhibitors are likely to have greater clinical efficacy in tumors with RAD17 loss
of-function.
PMID- 26437226
TI - Identification of novel, in vivo active Chk1 inhibitors utilizing structure
guided drug design.
AB - Chk1 kinase is a critical component of the DNA damage response checkpoint
especially in cancer cells and targeting Chk1 is a potential therapeutic
opportunity for potentiating the anti-tumor activity of DNA damaging chemotherapy
drugs. Fragment elaboration by structure guided design was utilized to identify
and develop a novel series of Chk1 inhibitors culminating in the identification
of V158411, a potent ATP-competitive inhibitor of the Chk1 and Chk2 kinases.
V158411 abrogated gemcitabine and camptothecin induced cell cycle checkpoints,
resulting in the expected modulation of cell cycle proteins and increased cell
death in cancer cells. V158411 potentiated the cytotoxicity of gemcitabine,
cisplatin, SN38 and camptothecin in a variety of p53 deficient human tumor cell
lines in vitro, p53 proficient cells were unaffected. In nude mice, V158411
showed minimal toxicity as a single agent and in combination with irinotecan. In
tumor bearing animals, V158411 was detected at high levels in the tumor with a
long elimination half-life; no pharmacologically significant in vivo drug-drug
interactions with irinotecan were identified through analysis of the
pharmacokinetic profiles. V158411 potentiated the anti-tumor activity of
irinotecan in a variety of human colon tumor xenograft models without additional
systemic toxicity. These results demonstrate the opportunity for combining
V158411 with standard of care chemotherapeutic agents to potentiate the
therapeutic efficacy of these agents without increasing their toxicity to normal
cells. Thus, V158411 would warrant further clinical evaluation.
PMID- 26437227
TI - Simultaneous PET/MRI Imaging During Mouse Cerebral Hypoxia-ischemia.
AB - Dynamic changes in tissue water diffusion and glucose metabolism occur during and
after hypoxia in cerebral hypoxia-ischemia reflecting a bioenergetics disturbance
in affected cells. Diffusion weighted magnetic resonance imaging (MRI) identifies
regions that are damaged, potentially irreversibly, by hypoxia-ischemia.
Alterations in glucose utilization in the affected tissue may be detectable by
positron emission tomography (PET) imaging of 2-deoxy-2-(18F)fluoro-?-glucose
([18F]FDG) uptake. Due to the rapid and variable nature of injury in this animal
model, acquisition of both modes of data must be performed simultaneously in
order to meaningfully correlate PET and MRI data. In addition, inter-animal
variability in the hypoxic-ischemic injury due to vascular differences limits the
ability to analyze multi-modal data and observe changes to a group-wise approach
if data is not acquired simultaneously in individual subjects. The method
presented here allows one to acquire both diffusion-weighted MRI and [18F]FDG
uptake data in the same animal before, during, and after the hypoxic challenge in
order to interrogate immediate physiological changes.
PMID- 26437228
TI - Time Out-of-Home and Cognitive, Physical, and Emotional Wellbeing of Older
Adults: A Longitudinal Mixed Effects Model.
AB - BACKGROUND: Time out-of-home has been linked with numerous health outcomes,
including cognitive decline, poor physical ability and low emotional state.
Comprehensive characterization of this important health metric would potentially
enable objective monitoring of key health outcomes. The objective of this study
is to determine the relationship between time out-of-home and cognitive status,
physical ability and emotional state. METHODS AND FINDINGS: Participants included
85 independent older adults, age 65-96 years (M = 86.36; SD = 6.79) who lived
alone, from the Intelligent Systems for Assessing Aging Changes (ISAAC) and the
ORCATECH Life Laboratory cohorts. Factors hypothesized to affect time out-of-home
were assessed on three different temporal levels: yearly (cognitive status,
loneliness, clinical walking speed), weekly (pain and mood) or daily (time out-of
home, in-home walking speed, weather, and season). Subject characteristics
including age, race, and gender were assessed at baseline. Total daily time out
of-home in hours was assessed objectively and unobtrusively for up to one year
using an in-home activity sensor platform. A longitudinal tobit mixed effects
regression model was used to relate daily time out-of-home to cognitive status,
physical ability and emotional state. More hours spend outside the home was
associated with better cognitive function as assessed using the Clinical Dementia
Rating (CDR) Scale, where higher scores indicate lower cognitive function
(betaCDR = -1.69, p<0.001). More hours outside the home was also associated with
superior physical ability (betaPain = -0.123, p<0.001) and improved emotional
state (betaLonely = -0.046, p<0.001; betaLow mood = -0.520, p<0.001). Weather,
season, and weekday also affected the daily time out-of-home. CONCLUSIONS: These
results suggest that objective longitudinal monitoring of time out-of-home may
enable unobtrusive assessment of cognitive, physical and emotional state. In
addition, these results indicate that the factors affecting out-of-home behavior
are complex, with factors such as living environment, weather and season
significantly affecting time out-of-home. Studies investigating the relationship
between time out-of-home and health outcomes may be optimized by taking into
account the environment and life factors presented here.
PMID- 26437230
TI - Duloxetine enters the brain - But why is it not found in the cerebrospinal fluid.
AB - BACKGROUND: Antidepressants enter the brain to reach their site of action in a
different extent. However, there has been no study to date about duloxetine's
ability to enter the brain and cerebrospinal fluid. Aim of this study was to
measure blood and cerebrospinal fluid concentrations of duloxetine and to account
for the distribution between the two compartments. METHODS: Concentrations of
duloxetine were measured in blood serum and cerebrospinal fluid of 19 patients
treated with daily doses of 30-120mg. Daily doses were correlated with serum and
cerebrospinal fluid concentrations and serum concentrations were correlated with
concentrations in cerebrospinal fluid. RESULTS: Serum concentrations of
duloxetine showed a moderate but significant correlation with the applied daily
dose, r=+0.473, p=0.04. Duloxetine concentrations in the cerebrospinal fluid
above the designated limit of quantification of 2.0ng/mL were only found in three
of the 19 patients. CONCLUSIONS AND LIMITATIONS: Contrasting to own preceding
studies on venlafaxine, mirtazapine and citalopram with comparably high
concentrations in cerebrospinal fluid, the here presented findings indicate that
duloxetine shows a very different distribution pattern. Very low concentrations
in the cerebrospinal fluid may be due to the fact that the drug crosses the blood
cerebrospinal fluid barrier much worse than other antidepressants do, suggesting
a low ability of duloxetine to enter the brain. Alternatively, low drug
concentrations may be interpreted in a sense of a missing residence time in
cerebrospinal fluid due to active transport mechanisms out of this environment
either back into the bloodstream or into the brain.
PMID- 26437229
TI - Optimizing Production of Antigens and Fabs in the Context of Generating
Recombinant Antibodies to Human Proteins.
AB - We developed and optimized a high-throughput project workflow to generate
renewable recombinant antibodies to human proteins involved in epigenetic
signalling. Three different strategies to produce phage display compatible
protein antigens in bacterial systems were compared, and we found that in vivo
biotinylation through the use of an Avi tag was the most productive method. Phage
display selections were performed on 265 in vivo biotinylated antigen domains.
High-affinity Fabs (<20nM) were obtained for 196. We constructed and optimized a
new expression vector to produce in vivo biotinylated Fabs in E. coli. This
increased average yields up to 10-fold, with an average yield of 4 mg/L. For 118
antigens, we identified Fabs that could immunoprecipitate their full-length
endogenous targets from mammalian cell lysates. One Fab for each antigen was
converted to a recombinant IgG and produced in mammalian cells, with an average
yield of 15 mg/L. In summary, we have optimized each step of the pipeline to
produce recombinant antibodies, significantly increasing both efficiency and
yield, and also showed that these Fabs and IgGs can be generally useful for
chromatin immunoprecipitation (ChIP) protocols.
PMID- 26437231
TI - Emotion-relevant impulsivity predicts sustained anger and aggression after
remission in bipolar I disorder.
AB - Recent evidence suggests that anger and aggression are of concern even during
remission for persons with bipolar I disorder, although there is substantial
variability in the degree of anger and aggression across individuals. Little
research is available to examine psychological models of anger and aggression for
those with remitted bipolar disorder, and that was the goal of this study.
Participants were 58 persons diagnosed with bipolar I disorder using the
Structured Clinical Interview for DSM-IV, who were followed with monthly symptom
severity interviews until they achieved remission, and then assessed using the
Aggression-Short Form. We examined traditional predictors of clinical parameters
and trauma exposure, and then considered three trait domains that have been shown
to be elevated in bipolar disorder and have also been linked to aggression
outside of bipolar disorder: emotion-relevant impulsivity, approach motivation,
and dominance-related constructs. Emotion-relevant impulsivity was related to
anger, hostility, verbal aggression, and physical aggression, even after
controlling for clinical variables. Findings extend the importance of emotion
relevant impulsivity to another important clinical outcome and suggest the
promise of using psychological models to understand the factors driving
aggression and anger problems that persist into remission among persons with
bipolar disorder.
PMID- 26437232
TI - White matter microstructural characteristics in Bipolar I and Bipolar II
Disorder: A diffusion tensor imaging study.
AB - BACKGROUND: Diffusion tensor imaging (DTI) studies of bipolar disorder (BD)
report contrasting results and are mainly focused on bipolar I (BD-I) samples. We
aimed at investigating how and where DTI parameters differ between BD-I and
bipolar II (BD-II) and between BD and healthy control subjects (HC). METHODS: We
conducted a tract-based spatial statistics analysis of DTI derived parameters,
namely fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity
(RD) in a matched sample of 50 BD (25 BD-I and 25 BD-II) during the chronic
course of the illness and 50 HC. RESULTS: Compared to BD-I and HC, BD-II showed
lower FA but no significant AD or RD differences in the right inferior
longitudinal fasciculus (ILF). Both patient groups showed lower AD and RD in the
left internal capsule and lower AD across the left ILF, the cortico-spinal tract
within the right hemisphere and bilaterally in the cerebellum with respect to HC.
LIMITATIONS: Patients were medicated at the time of scanning; the BD-II group had
higher Hamilton Rating Scale for Depression scores than the BD-I group.
CONCLUSIONS: BD-II patients differ from BD-I in the ILF. Both BD subtypes showed
widespread white matter (WM) changes in the internal capsule, cortico-spinal
tract and cerebellum. The loss of WM integrity in BD-II might be due to
demyelination whereas WM changes common to both subgroups could be attributable
to axonal damage.
PMID- 26437233
TI - Computerized cognitive training and functional recovery in major depressive
disorder: A meta-analysis.
AB - OBJECTIVE: Depression is common, frequently resistant to antidepressant
treatment, and associated with impairments in cognition and everyday functioning.
Computerized cognitive training (CCT) paradigms offer potential to improve
cognition, mood and everyday functioning, but their effectiveness is not well
established. The goal of this article was to conduct a systematic review and meta
analysis to determine the efficacy of CCT in depressive disorders. METHOD: A
search was conducted to identify high quality randomized controlled CCT trials
per PRISMA guidelines using PsycINFO and MEDLINE with the keywords "Cognitive
training" or "Cognitive remediation" or "Cognitive rehabilitation" and
"Depression". 9 randomized trials for depressed adults met inclusion criteria.
Effect sizes (Hedge's g) were calculated for key outcome measures of mood symptom
severity, daily functioning, and cognition. A 3-level Bayesian hierarchical
linear model was used to estimate effect sizes for each domain and study.
Publication bias was assessed using Classic Fail Safe N's and homogeneity was
evaluated using Q and I(2) indexes. RESULTS: Significant small-moderate effects
for Symptom Severity (0.43) and Daily Functioning (0.72), and moderate-large
effects for Attention (0.67), Working Memory (0.72), and Global Functioning
(1.05) were found. No significant effects were found for Executive Functioning or
Verbal Memory. Moderator variable analysis revealed decreased effect of CCT with
age. Gender and concurrent medication treatment did not affect the results.
LIMITATIONS: Small sample size, short duration, pseudo-specificity, and high
heterogeneity for Verbal Memory measures. CONCLUSIONS: CCT is associated with
improvement in depressive symptoms and everyday functioning, though produces
inconsistent effects on cognition.
PMID- 26437234
TI - Steroids for chronic inflammatory demyelinating polyradiculoneuropathy: evidence
base and clinical practice.
AB - Evidence-based therapies for chronic inflammatory demyelinating
polyradiculoneuropathy (CIDP) consist of corticosteroids, intravenous
immunglobulins (IVIg), and plasma exchange. Steroids represent the oldest
treatment used historically. In countries where readily available and affordable,
IVIg tends to be favored as first-line treatment. The reason for this preference,
despite substantially higher costs, is the perception that IVIg is more
efficacious and safer than corticosteroids. However, the unselected use of IVIg
as a first-line treatment option in all cases of CIDP raises issues of cost
effectiveness in the long-term. Furthermore, serious although rare, particularly
thromboembolic side effects may result from their use. Recent data from
randomized trials suggest pulsed corticosteroids to have a higher potential in
achieving therapy-free remission or longer remission-free periods compared with
IVIg, as well as relatively low rates of serious side effects when given as
pulsed intravenous infusions during short periods of time. These specific
advantages suggest that pulsed steroids could in many cases be used, as the
first, rather than second choice of treatment when initiating immunomodulation in
CIDP, primarily in hopes of achieving a remission after the short-term use. This
article reviews the evidence base for the use of corticosteroids in its various
forms in CIDP and factors that may influence clinicians' choice between IVIg and
pulsed steroid treatment. The issue of efficacy, relapse rate and time, and side
effect profile are analyzed, and some aspects from the authors' experience are
discussed in relation to the possibility of using the steroid option as first
line therapy in a large proportion of patients with CIDP.
PMID- 26437235
TI - A systems approach to understanding human rhinovirus and influenza virus
infection.
AB - Human rhinovirus and influenza virus infections of the upper airway lead to colds
and the flu and can trigger exacerbations of lower airway diseases including
asthma and chronic obstructive pulmonary disease. Novel diagnostic and
therapeutic targets are still needed to differentiate between the cold and the
flu, since the clinical course of influenza can be severe while that of
rhinovirus is usually more mild. In our investigation of influenza and rhinovirus
infection of human respiratory epithelial cells, we used a systems approach to
identify the temporally changing patterns of host gene expression from these
viruses. After infection of human bronchial epithelial cells (BEAS-2B) with
rhinovirus, influenza virus or co-infection with both viruses, we studied the
time-course of host gene expression changes over three days. We modeled host
responses to these viral infections with time and documented the qualitative and
quantitative differences in innate immune activation and regulation.
PMID- 26437236
TI - PCB Food Web Dynamics Quantify Nutrient and Energy Flow in Aquatic Ecosystems.
AB - Measuring in situ nutrient and energy flows in spatially and temporally complex
aquatic ecosystems represents a major ecological challenge. Food web structure,
energy and nutrient budgets are difficult to measure, and it is becoming more
important to quantify both energy and nutrient flow to determine how food web
processes and structure are being modified by multiple stressors. We propose that
polychlorinated biphenyl (PCB) congeners represent an ideal tracer to quantify in
situ energy and nutrient flow between trophic levels. Here, we demonstrate how an
understanding of PCB congener bioaccumulation dynamics provides multiple direct
measurements of energy and nutrient flow in aquatic food webs. To demonstrate
this novel approach, we quantified nitrogen (N), phosphorus (P) and caloric
turnover rates for Lake Huron lake trout, and reveal how these processes are
regulated by both growth rate and fish life history. Although minimal nutrient
recycling was observed in young growing fish, slow growing, older lake trout (>5
yr) recycled an average of 482 Tonnes.yr(-1) of N, 45 Tonnes.yr(-1) of P and
assimilated 22 TJ yr(-1) of energy. Compared to total P loading rates of 590
Tonnes.yr(-1), the recycling of primarily bioavailable nutrients by fish plays an
important role regulating the nutrient states of oligotrophic lakes.
PMID- 26437237
TI - Direct Observation of Highly Ordered Dendrimer Soft Building Blocks over a Large
Area.
AB - Developing large-area, single domain of organic soft-building blocks such as
block copolymers, colloids, and supramolecular materials is one of the most
important issues in the materials science and nanotechnology. Owing to their
small sizes, complex molecular architectures, and high mobility, supramolecular
materials are not well-suited for building large area, single domain structures.
In the described study, a single domain of supramolecular columnar dendrimers was
created over large area. The columnar structures in these domains have smaller
(4.5 nm) diameters, higher area densities (ca. 36 Tera-dots/in(2)) and larger
domains (>0.1 * 0.1 mm(2)) than those of all existing BCP and colloidal
assemblies. By simply annealing dendrimer thin films between two flat solid
surfaces, single domains of hexagonal columnar structures are created over large
macroscopic areas. Observations made in this effort should serve as the
foundation for the design of new routes for bottom-up lithography based on
supramolecular building blocks.
PMID- 26437238
TI - Stonin1 mediates endocytosis of the proteoglycan NG2 and regulates focal adhesion
dynamics and cell motility.
AB - Cellular functions, ranging from focal adhesion (FA) dynamics and cell motility
to tumour growth, are orchestrated by signals cells receive from outside via cell
surface receptors. Signalling is fine-tuned by the exo-endocytic cycling of these
receptors to control cellular responses such as FA dynamics, which determine cell
motility. How precisely endocytosis regulates turnover of the various cell
surface receptors remains unclear. Here we identify Stonin1, an endocytic adaptor
of unknown function, as a regulator of FA dynamics and cell motility, and
demonstrate that it facilitates the internalization of the oncogenic proteoglycan
NG2, a co-receptor of integrins and platelet-derived growth factor receptor.
Embryonic fibroblasts obtained from Stonin1-deficient mice display a marked
surface accumulation of NG2, increased cellular signalling and defective FA
disassembly as well as altered cellular motility. These data establish Stonin1 as
a specific adaptor for the endocytosis of NG2 and as an important factor for FA
dynamics and cell migration.
PMID- 26437239
TI - North American tree squirrels and ground squirrels with overlapping ranges host
different Cryptosporidium species and genotypes.
AB - Wildlife-associated Cryptosporidium are an emerging cause of cryptosporidiosis in
humans. The present study was undertaken to determine the extent to which North
American tree squirrels and ground squirrels host zoonotic Cryptosporidium
species and genotypes. Fragments of the Cryptosporidium 18S rRNA and actin genes
were amplified and sequenced from fecal samples obtained from three tree squirrel
and three ground squirrel species. In tree squirrels, Cryptosporidium was
identified in 40.5% (17/42) of American red squirrels (Tamiasciurus hudsonicus),
40.4% (55/136) of eastern gray squirrels (Sciurus carolinensis), and 28.6% (2/7)
of fox squirrels (Sciurus niger). Human-pathogenic Cryptosporidium ubiquitum and
Cryptosporidium skunk genotype were the most prevalent species/genotypes in tree
squirrels. Because tree squirrels live in close proximity to humans and are
frequently infected with potentially zoonotic Cryptosporidium species/genotypes,
they may be a significant reservoir of infection in humans. In ground squirrels,
Cryptosporidium was detected in 70.2% (33/47) of 13-lined ground squirrels
(Ictidomys tridecemlineatus), 35.1% (27/77) of black-tailed prairie dogs (Cynomys
ludovicianus), and the only golden-mantled ground squirrel (Callospermophilus
lateralis) that was sampled. Cryptosporidium rubeyi and ground squirrel genotypes
I, II, and III were identified in isolates from these ground squirrel species. In
contrast to the Cryptosporidium infecting tree squirrels, these species/genotypes
appear to be specific for ground squirrels and are not associated with human
disease.
PMID- 26437240
TI - Drosha controls dendritic cell development by cleaving messenger RNAs encoding
inhibitors of myelopoiesis.
AB - To investigate if the microRNA (miRNA) pathway is required for dendritic cell
(DC) development, we assessed the effect of ablating Drosha and Dicer, the two
enzymes central to miRNA biogenesis. We found that while Dicer deficiency had
some effect, Drosha deficiency completely halted DC development and halted
myelopoiesis more generally. This indicated that while the miRNA pathway did have
a role, it was a non-miRNA function of Drosha that was particularly critical.
Drosha repressed the expression of two mRNAs encoding inhibitors of myelopoiesis
in early hematopoietic progenitors. We found that Drosha directly cleaved stem
loop structure within these mRNAs and that this mRNA degradation was necessary
for myelopoiesis. We have therefore identified a mechanism that regulates the
development of DCs and other myeloid cells.
PMID- 26437241
TI - The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell
dependent emphysema.
AB - Smoking-related emphysema is a chronic inflammatory disease driven by the T(H)17
subset of helper T cells through molecular mechanisms that remain obscure. Here
we explored the role of the microRNA miR-22 in emphysema. We found that miR-22
was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema
and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate
carbon black (nCB) through a mechanism that involved the transcription factor NF
kappaB. Mice deficient in miR-22, but not wild-type mice, showed attenuated
T(H)17 responses and failed to develop emphysema after exposure to smoke or nCB.
We further found that miR-22 controlled the activation of APCs and T(H)17
responses through the activation of AP-1 transcription factor complexes and the
histone deacetylase HDAC4. Thus, miR-22 is a critical regulator of both emphysema
and T(H)17 responses.
PMID- 26437242
TI - Control of peripheral tolerance by regulatory T cell-intrinsic Notch signaling.
AB - Receptors of the Notch family direct the differentiation of helper T cell
subsets, but their influence on regulatory T cell (T(reg) cell) responses is
obscure. We found here that lineage-specific deletion of components of the Notch
pathway enhanced T(reg) cell-mediated suppression of type 1 helper T cell (T(H)1
cell) responses and protected against their T(H)1 skewing and apoptosis. In
contrast, expression in T(reg) cells of a gain-of-function transgene encoding the
Notch1 intracellular domain resulted in lymphoproliferation, exacerbated T(H)1
responses and autoimmunity. Cell-intrinsic canonical Notch signaling impaired
T(reg) cell fitness and promoted the acquisition by T(reg) cells of a T(H)1 cell
like phenotype, whereas non-canonical Notch signaling dependent on the adaptor
Rictor activated the kinase AKT-transcription factor Foxo1 axis and impaired the
epigenetic stability of Foxp3. Our findings establish a critical role for Notch
signaling in controlling peripheral T(reg) cell function.
PMID- 26437243
TI - Regulation of bifurcating B cell trajectories by mutual antagonism between
transcription factors IRF4 and IRF8.
AB - Upon recognition of antigen, B cells undertake a bifurcated response in which
some cells rapidly differentiate into plasmablasts while others undergo affinity
maturation in germinal centers (GCs). Here we identified a double-negative
feedback loop between the transcription factors IRF4 and IRF8 that regulated the
initial developmental bifurcation of activated B cells as well as the GC
response. IRF8 dampened signaling via the B cell antigen receptor (BCR),
facilitated antigen-specific interaction with helper T cells, and promoted
antibody affinity maturation while antagonizing IRF4-driven differentiation of
plasmablasts. Genomic analysis revealed concentration-dependent actions of IRF4
and IRF8 in regulating distinct gene-expression programs. Stochastic modeling
suggested that the double-negative feedback was sufficient to initiate
bifurcation of the B cell developmental trajectories.
PMID- 26437248
TI - CORRIGENDUM: Whole-exome sequencing reveals diverse modes of inheritance in
sporadic mild to moderate sensorineural hearing loss in a pediatric population.
PMID- 26437244
TI - T cell receptor reversed polarity recognition of a self-antigen major
histocompatibility complex.
AB - Central to adaptive immunity is the interaction between the alphabeta T cell
receptor (TCR) and peptide presented by the major histocompatibility complex
(MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling
constraints, the TCR universally adopts a canonical polarity atop the MHC. We
report the structures of two TCRs, derived from human induced T regulatory
(iT(reg)) cells, complexed to an MHC class II molecule presenting a proinsulin
derived peptide. The ternary complexes revealed a 180 degrees polarity reversal
compared to all other TCR-peptide-MHC complex structures. Namely, the iT(reg) TCR
alpha-chain and beta-chain are overlaid with the alpha-chain and beta-chain of
MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide
reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact
with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding
that fundamentally challenges our understanding of TCR recognition.
PMID- 26437245
TI - Ensemble Methods Enable a New Definition for the Solution to Gas-Phase Transfer
of Intrinsically Disordered Proteins.
AB - Intrinsically disordered proteins (IDPs) are important for health and disease,
yet their lack of net structure precludes an understanding of their function
using classical methods. Gas-phase techniques provide a promising alternative to
access information on the structure and dynamics of IDPs, but the fidelity to
which these methods reflect the solution conformations of these proteins has been
difficult to ascertain. Here we use state of the art ensemble techniques to
investigate the solution to gas-phase transfer of a range of different IDPs. We
show that IDPs undergo a vast conformational space expansion in the absence of
solvent to sample a conformational space 3-5 fold broader than in solution.
Moreover, we show that this process is coupled to the electrospray ionization
process, which brings about the generation of additional subpopulations for these
proteins not observed in solution due to competing effects on protein charge and
shape. Ensemble methods have permitted a new definition of the solution to gas
phase transfer of IDPs and provide a roadmap for future investigations into
flexible systems by mass spectrometry.
PMID- 26437250
TI - Microsphaeropsis arundinis skin and soft tissue infection in renal transplant
recipients: three case reports and a review of the literature.
AB - Microsphaeropsis arundinis, a dematiaceous mold, is emerging as a cause of skin
and soft tissue infection in immunocompromised hosts. Diagnosis is challenging
because of the difficulty in identifying Microsphaeropsis species morphologically
and few data are available to guide optimal management. We report 3 renal
transplant recipients with M. arundinis soft tissue infection, where the
etiological agent was diagnosed using DNA sequencing, and who were successfully
treated with prolonged courses of extended-spectrum triazole antifungal agents.
PMID- 26437252
TI - The role of junior doctors in medical education.
PMID- 26437251
TI - The Importance of Rare Subtypes in Diagnosis and Treatment of Peripheral
Neuropathy: A Review.
AB - IMPORTANCE: Peripheral neuropathy is a prevalent condition that usually warrants
a thorough history and examination but has limited diagnostic evaluation.
However, rare localizations of peripheral neuropathy often require more extensive
diagnostic testing and different treatments. OBJECTIVE: To describe rare
localizations of peripheral neuropathy, including the appropriate diagnostic
evaluation and available treatments. EVIDENCE REVIEW: References were identified
from PubMed searches conducted on May 29, 2015, with an emphasis on systematic
reviews and randomized clinical trials. Articles were also identified through the
use of the authors' own files. Search terms included common rare neuropathy
localizations and their causes, as well as epidemiology, pathophysiology,
diagnosis, and treatment. FINDINGS: Diffuse, nonlength-dependent neuropathies,
multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus
neuropathies are rare peripheral neuropathy localizations that often require
extensive diagnostic testing. Atypical neuropathy features, such as
acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently
present. The most common diffuse, nonlength-dependent neuropathies are Guillain
Barre syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal
motor neuropathy, and amyotrophic lateral sclerosis. Effective disease-modifying
therapies exist for many diffuse, nonlength-dependent neuropathies including
Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy,
multifocal motor neuropathy, and some paraprotein-associated demyelinating
neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has
efficacious treatment options, but definitive evidence of a treatment effect for
IgM anti-MAG neuropathy and diabetic amyotrophy (radiculoplexus neuropathy) is
lacking. CONCLUSIONS AND RELEVANCE: Recognition of rare localizations of
peripheral neuropathy is essential given the implications for diagnostic testing
and treatment. Electrodiagnostic studies are an important early step in the
diagnostic evaluation and provide information on the localization and
pathophysiology of nerve injury.
PMID- 26437253
TI - Dual-Function Exocytosis Regulator Has Yet Another Job.
AB - A new study shows that synaptotagmins, known to regulate the fusion of
neurotransmitter vesicles with synaptic membranes, are also needed for the prior
tethering and priming of vesicles. Read the Research Article.
PMID- 26437254
TI - Silica nanoparticles inhibit brown adipocyte differentiation via regulation of
p38 phosphorylation.
AB - Nanoparticles are of great interest due to their wide variety of biomedical and
bioengineering applications. However, they affect cellular differentiation and/or
intracellular signaling when applied and exposed to target organisms or cells.
The brown adipocyte is a cell type important in energy homeostasis and thus
closely related to obesity. In this study, we assessed the effects of silica
nanoparticles (SNPs) on brown adipocyte differentiation. The results clearly
showed that brown adipocyte differentiation was significantly repressed by
exposure to SNPs. The brown adipocyte-specific genes as well as mitochondrial
content were also markedly reduced. Additionally, SNPs led to suppressed p38
phosphorylation during brown adipocyte differentiation. These effects depend on
the size of SNPs. Taken together, these results lead us to suggest that SNP has
anti-brown adipogenic effect in a size-dependent manner via regulation of p38
phosphorylation.
PMID- 26437255
TI - Neuroinflammatory Mechanisms Linking Pain and Depression.
AB - Depression and chronic pain have been estimated to co-occur in up to 80% of
patients suffering from these disorders, with this co-morbidity being more
disabling and more expensive to both patients and society than either disorder
alone. A number of neural substrates have been proposed to underlie this
association; however, there has been increased interest and support for a role of
neuroimmune and neuroinflammatory mechanisms as key players in this dyad. This
chapter will provide an overview of the clinical and preclinical data supporting
a role for neuroimmune alterations in depression-pain co-morbidity. We propose
that such changes may impact on the functioning of key brain regions modulating
emotional and nociceptive processing, thus resulting in the behavioural,
psychological and physical symptoms observed in patients exhibiting depression
and co-morbid pain.
PMID- 26437256
TI - Synthesis of Amylose-b-P2 VP Block Copolymers.
AB - A new class of rod-coil block copolymers is synthesized by chemoenzymatic
polymerization. In the first step, maltoheptaose, which acts as a primer for the
synthesis of amylose, is attached to poly(2-vinyl pyridine) (P2 VP). The
enzymatic polymerization of maltoheptaose is carried out by phosphorylase to
obtain amylose-b-P2 VP block copolymers. The block copolymer is characterized by
Fourier transform infrared spectroscopy, nuclear magnetic resonance, gel
permeation chromatography, and wide-angle X-ray scattering techniques. The
designed molecules combine the inclusion complexation ability of amylose with the
supramolecular complexation ability of P2 VP and therefore this kind of rod-coil
block copolymers can be used to generate well-organized novel self-assembled
structures.
PMID- 26437258
TI - Pain in Borderline Personality Disorder.
AB - Pain processing in patients with borderline personality disorder (BPD) is
abnormal primarily with respect to pain thresholds which are typically elevated
or perception of phasic nociceptive stimuli which is reduced. In spite of this
common finding, nonsuicidal self-injury (NSSI), often expressed as cutting, is a
hallmark sign of the disease and serves to release aversive inner tension. The
question thus arises, how does a painful stimulus release inner tension when
these patients feel less pain than healthy people? However, intensity
discrimination is normal in these patients. Imaging data have provided evidence
that inhibitory top-down modulation is increased in BPD patients, and that
processing of the affective-emotional pain component is altered. Recent studies
have focused on the role of pain, tissue injury and seeing blood in the context
of NSSI. Preliminary findings suggest a significant role of pain irrespective of
concomitant tissue injury, and of seeing blood expressed as a stronger immediate
stress release. Taken together, BPD patients exhibit altered pain processing that
can be assigned to altered processing of nociceptive stimuli in prefrontal and
limbic brain areas, which may help to mechanistically explain the clinical
behavior.
PMID- 26437257
TI - Clinical and Molecular Characterization of Brazilian Patients Suspected to Have
Lynch Syndrome.
AB - Lynch syndrome (LS) accounts for 3-5% of all colorectal cancers (CRC) and is
inherited in an autosomal dominant fashion. This syndrome is characterized by
early CRC onset, high incidence of tumors in the ascending colon, excess of
synchronous/metachronous tumors and extra-colonic tumors. Nowadays, LS is
regarded of patients who carry deleterious germline mutations in one of the five
mismatch repair genes (MMR), mostly in MLH1 and MSH2, but also in MSH6, PMS1 and
PMS2. To comprehensively characterize 116 Brazilian patients suspected for LS, we
assessed the frequency of germline mutations in the three minor genes MSH6, PMS1
and PMS2 in 82 patients negative for point mutations in MLH1 and MSH2. We also
assessed large genomic rearrangements by MLPA for detecting copy number
variations (CNVs) in MLH1, MSH2 and MSH6 generating a broad characterization of
MMR genes. The complete analysis of the five MMR genes revealed 45 carriers of
pathogenic mutations, including 25 in MSH2, 15 in MLH1, four in MSH6 and one in
PMS2. Eleven novel pathogenic mutations (6 in MSH2, 4 in MSH6 and one in PMS2),
and 11 variants of unknown significance (VUS) were found. Mutations in the MLH1
and MSH2 genes represented 89% of all mutations (40/45), whereas the three MMR
genes (MSH6, PMS1 and PMS2) accounted for 11% (5/45). We also investigated the
MLH1 p.Leu676Pro VUS located in the PMS2 interaction domain and our results
revealed that this variant displayed no defective function in terms of cellular
location and heterodimer interaction. Additionally, we assessed the tumor
phenotype of a subset of patients and also the frequency of CRC and extra-colonic
tumors in 2,365 individuals of the 116 families, generating the first
comprehensive portrait of the genetic and clinical aspects of patients suspected
of LS in a Brazilian cohort.
PMID- 26437259
TI - Self-assembled 20-nm (64)Cu-micelles enhance accumulation in rat glioblastoma.
AB - There is an urgent need to develop nanocarriers for the treatment of glioblastoma
multiforme (GBM). Using co-registered positron emission tomography (PET) and
magnetic resonance (MR) images, here we performed systematic studies to
investigate how a nanocarrier's size affects the pharmacokinetics and
biodistribution in rodents with a GBM xenograft. In particular, highly stable,
long-circulating three-helix micelles (3HM), based on a coiled-coil protein
tertiary structure, were evaluated as an alternative to larger nanocarriers.
While the circulation half-life of the 3HM was similar to 110-nm PEGylated
liposomes (t1/2=15.5 and 16.5h, respectively), the 20-nm micelles greatly
enhanced accumulation within a U87MG xenograft in nu/nu rats after intravenous
injection. After accounting for tumor blood volume, the extravasated
nanoparticles were quantified from the PET images, yielding ~0.77%ID/cm(3) for
the micelles and 0.45%ID/cm(3) for the liposomes. For GBM lesions with a volume
greater than 100mm(3), 3HM accumulation was enhanced both within the detectable
tumor and in the surrounding brain parenchyma. Further, the nanoparticle
accumulation was shown to extend to the margins of the GBM xenograft. In summary,
3HM provides an attractive nanovehicle for carrying treatment to GBM.
PMID- 26437262
TI - IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein
delivery.
AB - Dissolving microneedles are an attractive approach for non-invasive delivery of
drugs via the skin, particularly when the doses are in the microgram or low
milligram range. The aim of the study was to develop hyaluronan-based, monoclonal
IgG-loaded microneedles for intradermal delivery enabling efficient penetration
and rapid dissolution in the skin while preserving protein stability. Microscopic
analysis showed successful preparation of sharp microneedles with the tip length
of ~280 MUm and with up to 10% (w/w) of IgG content. The water content of the
microneedles was ~12% and was not affected by the protein content. The protein
distribution was uniform within microneedle tips and individual arrays but some
array-to-array variation of IgG level within a single preparation batch was
detected. After dissolution of microneedle arrays in PBS, N80% of protein was
recovered and no conformational changes were detected by fluorescence
spectroscopy. At submicron level, only weak and reversible interaction between HA
and IgG was found by asymmetric flow field flow fractionation analysis after the
dissolution of prepared microneedles. Although, the formation of insoluble micron
size particles was detected by flow imaging microscopy the IgG amount
incorporated into these particles was negligible (b5%). Finally, microneedles
were able to penetrate into the epidermis of ex vivo human skin followed by the
rapid dissolution of the microneedle tips in the skin. After 10 min of
application, the majority of the original tip length was dissolved and IgG and
hyaluronan were co-deposited until a depth of 150-200 MUm in the skin. In
conclusion, developed hyaluronan-based dissolving microneedles allow rapid
noninvasive intradermal protein delivery.
PMID- 26437261
TI - Hepatoma targeting peptide conjugated bio-reducible polymer complexed with
oncolytic adenovirus for cancer gene therapy.
AB - Despite adenovirus (Ad) vector's numerous advantages for cancer gene therapy,
such as high ability of endosomal escape, efficient nuclear entry mechanism, and
high transduction, and therapeutic efficacy, tumor specific targeting and
antiviral immune response still remain as a critical challenge in clinical
setting. To overcome these obstacles and achieve cancer-specific targeting, we
constructed tumor targeting bioreducible polymer, an arginine grafted bio
reducible polymer (ABP)-PEG-HCBP1, by conjugating PEGylated ABP with HCBP1
peptides which has high affinity and selectivity towards hepatoma. The ABP-PEG
HCBP1-conjugated replication incompetent GFP-expressing ad, (Ad/GFP)-ABP-PEG
HCBP1, showed a hepatoma cancer specific uptake and transduction compared to
either naked Ad/GFP or Ad/GFP-ABP. Competition assays demonstrated that Ad/GFP
ABP-PEG-HCBP1-mediated transduction was specifically inhibited by HCBP1 peptide
rather than coxsackie and adenovirus receptor specific antibody. In addition, ABP
PEG-HCBP1 can protect biological activity of Ad against serum, and considerably
reduced both innate and adaptive immune response against Ad. shMet-expressing
oncolytic Ad (oAd; RdB/shMet) complexed with ABP-PEG-HCBP1 delivered oAd
efficiently into hepatoma cancer cells. The oAd/ABP-PEG-HCBP1 demonstrated
enhanced cancer cell killing efficacy in comparison to oAd/ABP complex.
Furthermore, Huh7 and HT1080 cancer cells treated with oAd/shMet-ABP-PEG-HCBP1
complex had significantly decreased Met and VEGF expression in hepatoma cancer,
but not in non-hepatoma cancer. In sum, these results suggest that HCBP1
conjugated bioreducible polymer could be used to deliver oncolytic Ad safely and
efficiently to treat hepatoma.
PMID- 26437263
TI - Shape and size-dependent immune response to antigen-carrying nanoparticles.
AB - The immune system has evolved to recognize and respond to a wide variety of
pathogens and produce distinct immune responses against diverse pathogenic
structures. Despite remarkable advances, the general mechanisms by which the
immune system differentiates the structure of antigen presenting particulates
have yet to be elucidated. Using particles of various sizes and shapes, we
assessed the role of morphological features of particles in antigen presentation
and subsequent processing by the immune cells. Ovalbumin was used as a model
antigen. Spherical polystyrene particles of 193 nm and 521 nm diameters were
successfully stretched to form rod-shaped particles of 376 nm and 1530 nm in
length, respectively. Ovalbumin conjugation to these different particle types was
optimized to achieve ~50 MUg of ovalbumin conjugation per mg of particle. In vivo
immunization study results revealed that small spherical particles (193 nm in
diameter) produced a Th1-biased response whereas rod-shaped particles (1530 nm in
length) produced a Th2-biased response against ovalbumin. Among different
particle types, smaller spherical (193 nm) particles generated stronger Th1 and
Th2 immune responses compared to the other particle types. In vitro studies with
dendritic cells indicated that spherical (193 nm) and rod (1530 nm) shaped
particles were internalized by dendritic cells and delivered ovalbumin. These
results provide evidence for size- and shape-dependent modulation of immune
responses and this knowledge can be leveraged to rationally design and develop
next generation vaccines against a wide range of pathogens.
PMID- 26437260
TI - Design of smart HPMA copolymer-based nanomedicines.
AB - The state-of-the art in water-soluble macromolecular therapeutics has been
reviewed. First the design principles for polymer-drug conjugates are discussed
followed by two recent developments in the field: a) The design, synthesis and
properties of backbone degradable N-(2-hydroxypropyl)methacrylamide (HPMA)
copolymer-drug conjugates. The enhanced intravascular half-life of such
conjugates creates a concentration gradient (blood vs. tumor) for an extended
time interval resulting in increased solid tumor accumulation by enhanced
permeability and retention (EPR) effect with concomitant increase in efficacy. b)
Drug-free macromolecular therapeutics is a new paradigm in macromolecular
therapeutics. Apoptosis in malignant cell is induced by crosslinking of cell
surface non-internalizing receptors. Crosslinking of receptors is mediated by the
biorecognition of two nanoconjugates containing high-fidelity complementary
motifs (peptides or oligonucleotides). Results for the treatment of B cell
lymphomas in animal models and patient cells demonstrate the high translational
potential of this approach.
PMID- 26437264
TI - Degradation of Triazine-2-(14)C Metsulfuron-Methyl in Soil from an Oil Palm
Plantation.
AB - Triazine-2-(14)C metsulfuron-methyl is a selective, systemic sulfonylurea
herbicide. Degradation studies in soils are essential for the evaluation of the
persistence of pesticides and their breakdown products. The purpose of the
present study was to investigate the degradation of triazine-2-(14)C metsulfuron
methyl in soil under laboratory conditions. A High Performance Liquid
Chromatograph (HPLC) equipped with an UV detector and an on-line radio-chemical
detector, plus a Supelco Discovery column (250 x 4.6 mm, 5 MUm), and PRP-1 column
(305 x 7.0 mm, 10 MUm) was used for the HPLC analysis. The radioactivity was
determined by a Liquid Scintillation Counter (LSC) in scintillation fluid. The
soil used was both sterilized and non-sterilized in order to observe the
involvement of soil microbes. The estimated DT50 and DT90 values of metsulfuron
methyl in a non-sterile system were observed to be 13 and 44 days, whereas in
sterilized soil, the DT50 and DT90 were 31 and 70 days, respectively. The
principal degradation product after 60 days was CO2. The higher cumulative amount
of (14)CO2 in (14)C-triazine in the non-sterilized soil compared to that in the
sterile system suggests that biological degradation by soil micro-organisms
significantly contributes to the dissipation of the compound. The major routes of
degradation were O-demethylation, sulfonylurea bridge cleavage and the triazine
"ring-opened."
PMID- 26437265
TI - Treatment discontinuation with peg-interferon: what to consider.
AB - Eradication of chronic hepatitis C virus infection improves the outcome of both
liver and extrahepatic-related diseases and interferon-based regimens
represented, for years, the standard of care to achieve this goal. Several
baseline and on-treatment predictors of response, associated with a lower chance
to achieve sustained virological response after interferon-based treatment, were
developed. In the past few years, the advent of direct acting antivirals has
dramatically modified the landscape of antiviral therapy, leading to an evolution
from interferon-based to interferon-free therapies. This review will focus on the
usefulness of futility stopping rules that allow the discontinuation of therapy
in patients with a reduced chance to obtain sustained virological response if
treated with interferon-containing regimens.
PMID- 26437266
TI - Changes in liver acceptance patterns after implementation of Share 35.
AB - The Share 35 policy was implemented June 2013. We sought to evaluate liver offer
acceptance patterns of centers under this policy. We compared three 1-year eras
(1, 2, and 3) before and 1 era (4) after the implementation date of the Share 35
policy (June 18, 2013). We evaluated all offers for liver-only recipients
including only those offers for livers that were ultimately transplanted.
Logistic regression was used to develop a liver acceptance model. In era 3, there
were 4809 offers for Model for End-Stage Liver Disease (MELD) score >= 35
patients with 1071 acceptances (22.3%) and 10,141 offers and 1652 acceptances
(16.3%) in era 4 (P < 0.001). In era 3, there were 42,954 offers for MELD score <
35 patients with 4181 acceptances (9.7%) and 44,137 offers and 3882 acceptances
(8.8%) in era 4 (P < 0.001). The lower acceptance rate persisted across all
United Network for Organ Sharing regions and was significantly less in regions 2,
3, 4, 5, and 7. Mean donor risk index was the same (1.3) for all eras for MELD
scores >= 35 acceptances and the same (1.4) for MELD score < 35 acceptances.
Refusal reasons did not vary throughout the eras. The adjusted odds ratio of
accepting a liver for a MELD score of 35 + compared to a MELD score < 35 patient
was 1.289 before the policy and 0.960 after policy implementation. In conclusion,
the Share 35 policy has resulted in more offers to patients with MELD scores >=
35. Overall acceptance rates were significantly less compared to the same patient
group before the policy implementation. Centers are less likely to accept a liver
for a patient with a MELD score of 35 + after the policy change. Decreased donor
acceptance rates could reflect more programmatic selectivity and ongoing donor
and recipient matching.
PMID- 26437268
TI - Method of Studying Palatal Fusion using Static Organ Culture.
AB - Cleft lip and palate are among the most common of all birth defects. The
secondary palate forms from mesenchymal shelves covered with epithelium that
adheres to form the midline epithelial seam (MES). The theories suggest that MES
cells follow an epithelial to mesenchymal transition (EMT), apoptosis and
migration, making a fused palate (1). Complete disintegration of the MES is the
final essential phase of palatal confluence with surrounding mesenchymal cells.
We provide a method for palate organ culture. The developed in vitro protocol
allows the study of the biological and molecular processes during fusion. The
applications of this technique are numerous, including evaluating responses to
exogenous chemical agents, effects of regulatory and growth factors and specific
proteins. Palatal organ culture has a number of advantages including manipulation
at different stages of development that is not possible using in vivo studies.
PMID- 26437267
TI - INFLUENCE OF STUDY DESIGN ON TREATMENT RESPONSE IN ANXIETY DISORDER CLINICAL
TRIALS.
AB - OBJECTIVE: The influence of study design variables and publication year on
response to medication and placebo was investigated in clinical trials for social
anxiety disorder (SAD), generalized anxiety disorder (GAD), and panic disorder
(PD). METHOD: Hierarchical linear modeling determined whether publication year,
treatment assignment (medication vs. placebo), study type (placebo-controlled or
active comparator), study duration, and the number of study visits affected the
mean change associated with medication and placebo. RESULTS: In the 66 trials
examined, the change associated with both medication and placebo increased over
time (t = 4.23, df = 39, P < .001), but average drug-placebo differences
decreased over time (t = -2.04, df = 46, P = .047). More severe baseline illness
was associated with greater drug-placebo differences for serotonin norepinephrine
reuptake inhibitors (SNRIs, t = 3.46, df = 106, P = .001) and selective serotonin
reuptake inhibitors (SSRI, t = 10.37, df = 106, P < .001). Improvement with
medication was significantly greater in active-comparator studies compared to
placebo-controlled trials (t = 3.41, df = 39, P = .002). A greater number of
study visits was associated with greater symptom improvement in PD trials
relative to SAD (t = 2.83, df = 39, P = .008) and GAD (t = 2.16, df = 39, P =
.037). CONCLUSIONS: Placebo response is substantial in SAD, GAD, and PD trials,
and its rise over time has been associated with diminished drug-placebo
differences. Study design features that influence treatment response in anxiety
disorder trials include patient expectancy, frequency of follow-up visits, and
baseline illness severity.
PMID- 26437269
TI - Enhanced permeability of ferulic acid loaded nanoemulsion based gel through skin
against UVA mediated oxidative stress.
AB - AIMS: The study was aimed to develop a ferulic acid (FA) loaded nanoemulsion
based gel in order to ensure the enhanced permeability and maximum antioxidant
activity against UVA induced oxidative stress in rat. MAIN METHODS: The optimized
ferulic acid loaded nanoemulsion 3 (FA-NE3) was prepared by spontaneous nano
emulsification method with an appropriate ratio (20:30:50% w/w) of the oil
(isostearyl isostearate), aqueous system and Smix [surfactant (labrasol) and co
surfactant (plurol isostearique)] respectively. FA-NE3 was characterized by
measuring their droplet size, zeta potential, refractive index, transmission
electron microscopy (TEM), ultraviolet (UV), fourier transform infrared
spectroscopy (FTIR) and rheological characteristics. Ex vivo skin permeation and
in vivo UVA protection activity of FA-NE3 based nano-gels (FA-NG3) along with
placebo were studied through the rat skin. KEY FINDINGS: FA-NE3 exhibited
sustained-release profile, better permeability and ultraviolet A (UVA) protection
activity as compared to conventional dosage form. This phenomenon may be
attributed towards increased solubility of the drug and enhanced permeability
from nanoemulsion. FA-NE3 based nanogel (FA-NG3) could elevate the level of skin
marker enzymes against oxidative stress mediated by UVA. SIGNIFICANCE: The gel
formulation exhibited significant (P<0.01) skin permeability and antioxidant
activity in the current investigations. The nanogel could be promising
nanocarriers for topical delivery of FA in response to better skin protection
activity against UVA rays in a sustained manner.
PMID- 26437270
TI - Mechanistic evidence of Passiflora edulis (Passifloraceae) anxiolytic activity in
relation to its metabolite fingerprint as revealed via LC-MS and chemometrics.
AB - Passiflora edulis Sims F. flavicarpa along with several other plants belonging to
the genus Passiflora have been reported as sedatives and for treatment or
prevention of central disorders. This study evaluated the anxiolytic effect of P.
edulis ethanol extract and its fractions (viz. chloroform, ethyl acetate and
butanol) using the elevated plus-maze model of anxiety and assessment of gamma
aminobutyric acid levels. The results revealed that butanol and chloroform
extracts exhibit the strongest effect followed by ethyl acetate suggesting that a
combination of different classes of metabolites is likely to mediate for P.
edulis anxiolytic effect in these fractions. To further pinpoint bioactive agents
in fractions, ultra-performance liquid chromatography (UPLC) coupled to high
resolution qTOF-MS was used for secondary metabolite profiling. A total of 65
metabolites were characterized including O-flavonoids, C-flavonoids, cyanogenic
glycosides and fatty acids. Harman type alkaloids found in P. incarnata were not
detected in P. edulis ethanol extract or any of its fractions suggesting that
they do not mediate for its CNS modulating effects. Multivariate data analysis
(PCA) was further applied to identify metabolite markers for fractions and
revealed that enrichment of C-glycoside type flavonoids in chloroform/ethyl
acetate fractions versus the exclusive presence of cyanogenic glycosides in its
butanol fraction.
PMID- 26437275
TI - Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model
Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired
Glucose Tolerance, or New Onset Diabetes After Transplantation.
AB - BACKGROUND: New onset diabetes after transplantation (NODAT) is associated with a
3-fold greater risk of cardiovascular disease events, with early identification
and treatment potentially attenuating this risk. The optimal screening test to
identify those with NODAT remains unclear, and the aim of this study was to
examine the diagnostic accuracies of 4 screening tests in identifying impaired
fasting glucose, impaired glucose tolerance (IGT), and NODAT. METHODS: This is a
single-center prospective cohort study of 83 nondiabetic kidney transplant
recipients between 2008 and 2011. Oral glucose tolerance test was considered the
gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random
blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model
Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using
the area under the receiver operating characteristic curve. RESULTS: Forty (48%)
recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the
curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine
was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The
adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin
Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to
identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66),
fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95%
CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of
0.88 (95% CI, 0.76-0.96). CONCLUSIONS: Although HBA1c is an acceptable and widely
used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more
accurate diagnostic test but this needs to be further examined in larger cohorts.
PMID- 26437278
TI - Evans Enolates: Solution Structures of Lithiated Oxazolidinone-Derived Enolates.
AB - The results of a combination of (6)Li and (13)C NMR spectroscopic and
computational studies of oxazolidinone-based lithium enolates-Evans enolates-in
tetrahydrofuran (THF) solution revealed a mixture of dimers, tetramers, and
oligomers (possibly ladders). The distribution depended on the structure of the
oxazolidinone auxiliary, substituent on the enolate, and THF concentration (in
THF/toluene mixtures). The unsolvated tetrameric form contained a D(2d)-symmetric
core structure, whereas the dimers were determined experimentally and
computationally to be trisolvates with several isomeric forms.
PMID- 26437279
TI - Generalized linear IgA dermatosis with palmar involvement.
AB - Linear IgA bullous dermatosis (LABD) is a sub-epidermal blistering disorder
characterized by deposition of IgA along the basement membrane zone (BMZ) as
detected by immunofluorescence microscopy. The diagnosis is made by
clinicopathologic correlation with immunofluorescence confirmation.
Differentiation from other bullous dermatoses is important because therapeutic
measures differ. Prompt initiation of the appropriate therapies can have a major
impact on outcomes. We present three cases with prominent palmar involvement to
alert the clinician of this potential physical exam finding and to consider LABD
in the right context.
PMID- 26437277
TI - Mfa4, an Accessory Protein of Mfa1 Fimbriae, Modulates Fimbrial Biogenesis, Cell
Auto-Aggregation, and Biofilm Formation in Porphyromonas gingivalis.
AB - Porphyromonas gingivalis, a gram-negative obligate anaerobic bacterium, is
considered to be a key pathogen in periodontal disease. The bacterium expresses
Mfa1 fimbriae, which are composed of polymers of Mfa1. The minor accessory
components Mfa3, Mfa4, and Mfa5 are incorporated into these fimbriae. In this
study, we characterized Mfa4 using genetically modified strains. Deficiency in
the mfa4 gene decreased, but did not eliminate, expression of Mfa1 fimbriae.
However, Mfa3 and Mfa5 were not incorporated because of defects in
posttranslational processing and leakage into the culture supernatant,
respectively. Furthermore, the mfa4-deficient mutant had an increased tendency to
auto-aggregate and form biofilms, reminiscent of a mutant completely lacking
Mfa1. Notably, complementation of mfa4 restored expression of structurally intact
and functional Mfa1 fimbriae. Taken together, these results indicate that the
accessory proteins Mfa3, Mfa4, and Mfa5 are necessary for assembly of Mfa1
fimbriae and regulation of auto-aggregation and biofilm formation of P.
gingivalis. In addition, we found that Mfa3 and Mfa4 are processed to maturity by
the same RgpA/B protease that processes Mfa1 subunits prior to polymerization.
PMID- 26437280
TI - Opioid associated intravenous and cutaneous microvascular drug abuse (skin
popping) masquerading as Degos disease (malignant atrophic papulosis) with
multiorgan involvement.
AB - BACKGROUND: In 2012, a nephrologist reported the development of a multiorgan
thrombotic syndromic complex resembling thrombotic thrombocytopenic purpura (TTP)
in patients who were abusing long acting oxymorphone hydrochloride; all patients
had hemolytic anemia and thrombocytopenia. OBJECTIVE: Herein, we report another
case involving a 31-year-old woman who self intravenously administered dissolved
oral oxymorphone resulting in thrombotic sequelae resembling Degos disease.
METHODS: Formalin-fixed and paraffin embedded skin biopsies were prepared
according to standard protocols for H&E and immunohistochemistry. RESULTS: The
clinical presentation and biopsy findings were held to be indicative of Degos
disease/malignant atrophic papulosis (MAP) but with unusual clinical features
including renal failure and severe respiratory insufficiency. Given the efficacy
of eculizumab in the treatment of the acute thrombotic phase of Degos
disease/MAP, the patient received this drug, resulting in rapid resolution of
signs and symptoms associated with her multiorgan failure. Although she developed
recurrent cutaneous ulcers despite complete complement inhibition with
eculizumab., her other extracutaneous manifestations did not recur. The patient's
pre and post eculizumab skin biopsies showed a striking pauci-inflammatory
thrombogenic vasculopathy associated with marked endothelial cell injury along
with deposits of C3d and C4d within the cutaneous vasculature; the C5b-9 deposits
were limited to the pre-eculizumab biopsy. We discovered that her syndromic
complex was a self-inflicted one related to the localized administration of
dissolved oxymorphone. CONCLUSION: Our patient's biopsy along with the rapid
response to eculizumab indicates that this distinct thrombotic microangiopathy is
another complement mediated thrombotic microangiopathy syndrome. Opioid
thrombotic microangiopathy has a varied clinical presentation and can mimic other
catastrophic microangiopathy syndromes, all of which have in common a
responsiveness to complement inhibition.
PMID- 26437281
TI - A 7-year-old with indurated skin and unilateral progressive joint immobility: A
case of stiff skin syndrome.
AB - Stiff skin syndrome is a rare sclerotic condition that presents during infancy or
early childhood. It has an insidious chronic course and may lead to significant
co-morbidity and reduced quality of life. Often, affected individuals experience
impaired ambulation and immobilization related to joint involvement. Clinically,
it may resemble other sclerotic diseases, so histopathological evaluation is
necessary to establish a diagnosis. As it is a condition with limited treatment
options, prompt diagnosis and early initiation of physical therapy is crucial to
prevent joint restriction and maintain quality of life. We describe a case of a 7
year-old with stiff skin syndrome, and review the literature to discuss the
clinical presentation, histological findings, and management of this condition.
PMID- 26437282
TI - Sporotrichoid granuloma annulare-like dermatitis associated with systemic B-cell
lymphoma.
AB - IMPORTANCE: Granuloma annulare is typically a benign, self-limited disease.
Atypical presentations have been reported in association with systemic disease,
including malignancy. Such patients may require additional diagnostic studies to
assess for underlying malignancy. We report a patient with extensive
sporotrichoid granuloma annulare-like dermatitis in association with systemic B
cell lymphoma. OBSERVATIONS: An 83-year-old man with a three-year history of
progressive sporotrichoid annular plaques and nodules on the arm developed
ipsilateral retroauricular palpable lymphadenopathy, the latter consistent with B
cell lymphoma. Multiple skin biopsies of the plaques and nodules revealed
granuloma annulare-like dermatitis. Lesions were unresponsive to intralesional
and intramuscular corticosteroids, antibiotics, and antifungal agents, but
rapidly improved following initiation of rituximab to treat his underlying
lymphoma. CONCLUSIONS AND RELEVANCE: Atypical presentations of granuloma annulare
including granuloma annulare-like dermatitis warrant evaluation for systemic
malignancy in a subset of patients.
PMID- 26437283
TI - Scleromyxedema secondary to hepatitis C virus and successfully treated with
antiviral therapy.
AB - Scleromyxedema (SM) is a chronic and progressive fibromucinous disease with no
known etiology. We report a patient with scleromyxedema associated with hepatitis
C virus, successfully treated with interferon and ribavirin therapy.
PMID- 26437284
TI - Phacomatosis cesiomarmorata with hypospadias and phacomatosis cesioflammea with
Sturge-Weber syndrome, Klippel-Trenaunay syndrome and aplasia of veins -- case
reports with rare associations.
AB - Phacomatosis pigmentovascularis (PPV) is a rare genodermatosis characterized by
the co-existence of an extensive vascular and a pigmentary nevus with or without
extracutaneous manifestations. We report two such rare cases. The first is a 3
year-old boy exhibiting a rare association of cutis marmorata telangiectatica
congenita with aberrant dermal melanocytosis along with hypospadias and melanosis
oculi (traditionally classified as PPV type Vb or phacomatosis cesiomarmorata -
Happle's classification). The other patient is a 5-year-old boy with Sturge-Weber
syndrome, Klippel-Trenaunay syndrome, aplasia of iliac, femoral, and popliteal
veins and congenital heart disease, associated with aberrant dermal melanocytosis
and melanosis oculi (also classified as PPV type IIb or phacomatosis
cesioflammea). These sporadic cases display a unique constellation of additional,
previously unreported systemic associations, which will further expand the
clinical spectrum of phacomatosis pigmentovascularis.
PMID- 26437285
TI - Eruptive milia and comedones during treatment with dovitinib.
AB - Dovitinib (TKI258) is a multi-targeted receptor tyrosine kinase inhibitor
currently under clinical trials for a wide variety of cancers. Well-known side
effects include nausea, vomiting, diarrhea, and fatigue. To date, there have only
been only two reported cases with skin manifestations as a side effect. We report
a case of eruptive facial milia and comedones in the setting of dovitinib
treatment for metastatic gastrointestinal cancer. This case is unique as the
clinical presentation was more rapid in onset and showed an absence of
inflammatory lesions. Although the pathogenesis for skin manifestations is
presently unknown, we present this case to increase awareness of potentially
under-reported cutaneous side effects.
PMID- 26437286
TI - Trichophytum rubrum endonyx onychomycosis resistant to standard oral and topical
therapies.
AB - We present a 45 year-old man with an eight-year history of discoloration of the
nail plate on his left hallux. He had been treated with two courses of oral
terbinafine and topical 8% ciclopirox for presumed onychomycosis. On exam, his
left great toenail contained a wide yellow-white longitudinal band involving a
majority of the nail plate. No subungual debris, hyperkeratosis, or paronychial
inflammation was present in the affected nail. Histopathology of the nail plate
revealed numerous fungal elements arranged transversely and longitudinally,
solely within the keratin layers of the nail plate; these were highlighted with
periodic acid-Schiff (PAS) stain confirming endonyx onychomycosis. Cultures grew
Trichophyton rubrum. All types of onychomycosis under the new classification
system proposed by Hay et al. have now been associated with T. rubrum. Endonyx
related to T. rubrum may be a particularly difficult infection to treat with oral
or topical agents owing to the absence of robust local immune response and
limited drug penetration to the interior nail plate. Physicians should be aware
that this type of infection may require treatment with dual-agent therapy or
alternative modalities including chemical or surgical plate avulsion or
photodynamic therapy.
PMID- 26437287
TI - Generalized lentiginosis in an 11 year old boy.
AB - Generalized lentiginosis refers to generalized lentigines without systemic
abnormalities, characterized by multiple brown or black macules owing to
increased proliferation of melanocytes. There are also lentiginosis syndromes
associated with systemic abnormalities such as Peutz-Jeghers syndrome, Leopard
syndrome, and Carney complex. Generalized lentiginosis can be diagnosis by
patient's history, physical and laboratory examination, and histopathology. We
report an 11-year-old boy who presented with multiple dark brown macules, varying
in size, but less than 0.5 cm, with no abnormalities of other systemic organs.
PMID- 26437288
TI - Bullous pilomatricoma: a rarely reported variant of pilomatricoma.
AB - Pilomatricomas are cutaneous adnexal tumors with matrical differentiation. We
report and describe a rare variant called bullous pilomatricoma.
PMID- 26437289
TI - Two sisters with Reed's syndrome: treatment with pregabalin.
AB - Cutaneous leiomyomas, which originate in the arrector pili muscles of the skin
are rarely seen benign cutaneous tumors. Sometimes familial cutaneous and uterine
leiomyomatosis can occur together, an autosomal dominant genetic condition called
Reed syndrome or familial leiomyomatosis cutis et uteri. This disorder can be
accompanied by malignancies, particularly by renal carcinoma. In this paper, two
sisters with Reed syndrome are presented in view of the rarity of the disorder
and good response to pregabalin therapy.
PMID- 26437290
TI - Localized and linear lichen planopilaris over the face and scalp with associated
alopecia - clinical and dermoscopy pattern.
AB - A case of localized lichen planopilaris over the face, extending to the scalp is
presented.This case highlights the different variations, which can occur in the
presentation of localized lichen planus. The case was unique because of the
extension of the lesions into the scalp. We also wanted to demonstrate the
peculiar dermoscopic patterns of active lichen planopilaris when occurring over
the face.
PMID- 26437291
TI - What is the prognostic significance of acrometastases?
AB - In contrast with bone metastasis, acrometastases are uncommon and are associated
with advanced cancer. We report the cases of two patients with atypical lesions
of the fingers in a context of cancer, in which biopsies confirmed a metastasis.
Patients died rapidly before treatment was initiated. We discuss the
characteristics of these atypical metastatic sites, associated with a generally
poor prognosis.
PMID- 26437292
TI - Immediate resolution of severe bullous chronic regional pain syndrome with onset
of spinal paralysis.
AB - Complex regional pain syndrome (CRPS) is an incompletely understood disorder
characterized by progressive regional pain and sensory changes, with fluctuating
cutaneous edema and erythema. We describe a patient with a rarely reported severe
bullous CRPS variant on the left lower extremity, which resolved immediately upon
developing spinal paralysis.
PMID- 26437293
TI - Even well-controlled psoriasis patients have unmet treatment needs regardless of
disease severity.
AB - BACKGROUND: Though psoriasis is chronic and recurring, current options can help
many patients achieve good disease control. New treatments could provide greater
improvement in objective disease, but it is not clear that there is room for
improving subjective outcomes, particularly for patients who are already "well
controlled." OBJECTIVE: To analyze treatment satisfaction of well-controlled
patients with psoriasis in two patient populations of very different disease
severity. METHODS: Patients with well-controlled psoriasis on topicals (mild
psoriasis) only or on biologics (moderate-to-severe psoriasis) were queried by
telephone about perceptions of disease control, improvement level, overall
treatment satisfaction, and consideration for trying new treatments. Satisfaction
scores and feedback were analyzed to assess treatment type and satisfaction level
associations. RESULTS: The majority of patients, regardless of disease severity,
would consider trying new treatments for psoriasis, though patients with mild
psoriasis were less satisfied with their disease control, level of improvement,
and overall treatment. Patient feedback revealed widespread treatment
dissatisfaction, non-adherence, and inconvenience. LIMITATIONS: The patient
population was from one university setting. CONCLUSION: 16% of patients with
psoriasis meet study definition for "well-controlled" disease. Less than 20% of
these well- controlled patients with psoriasis are satisfied with their current
level of control and clearance and would not consider trying new treatments,
suggesting the majority of well-controlled patients, regardless of disease
severity, still have unmet needs. Stronger patient-physician communication may
contribute to patient-based, comprehensive care in concordance with a health
system that is headed towards financial incentives for better patient
satisfaction.
PMID- 26437294
TI - Additional evidence that rosacea pathogenesis may involve demodex: new
information from the topical efficacy of ivermectin and praziquantel.
AB - Additional evidence that Demodex folliculorum may contribute to the pathogenesis
of papulopustular rosacea are new studies of two topical antiparasitic agents.
Ivermectin and praziquantel have recently been shown to be effective in
decreasing the severity of papulopustular rosacea. These two agents significantly
differ in molecular structure, but yield similar antiparasitic mechanisms of
action. Higher numbers of Demodex mites are found in the skin of patients with
rosacea than in people with normal skin. If Demodex play a role in pathogenesis,
then hypersensitivity to the mites, their flora, or their products could explain
the observed efficacy of antidemodectic therapy.
PMID- 26437295
TI - Generalized pruritus in dysmetabolic hyperferritinemia treated by phlebotomy.
AB - This paper describes a case of pruritus caused by dysmetabolic hyperferritinemia
treated by multiple phlebotomies. A 63-year-old man was followed for generalized
pruritus, which was resistant to the usual treatments. He presented with
metabolic syndrome. Physical examination showed only excoriations and
lichenification on the skin. The serum ferritin was high at 1043 ng/ml, with
transferrin saturation at 67%. The other biological investigations and genetic
tests for hemochromatosis were negative. In spite of the dietary measures, the
ferritin level was still high (853 ng/ml). Magnetic resonance imaging confirmed
hepatic iron overload.The association of hyperferritinemia, hepatic iron
overload, and metabolic syndrome led to the diagnosis of dysmetabolic
hyperferritinemia. Phlebotomies are an unusual treatment, but because the
pruritus and hyperferritinemia were still present, phlebotomy was initiated.
After 19 months, the patient reported improvement of his pruritus and
normalization of ferritin levels.
PMID- 26437297
TI - Exploring three-dimensional orbital imaging with energy-dependent photoemission
tomography.
AB - Recently, it has been shown that experimental data from angle-resolved
photoemission spectroscopy on oriented molecular films can be utilized to
retrieve real-space images of molecular orbitals in two dimensions. Here, we
extend this orbital tomography technique by performing photoemission initial
state scans as a function of photon energy on the example of the brickwall
monolayer of 3,4,9,10-perylene tetracarboxylic dianhydride (PTCDA) on Ag(110).
The overall dependence of the photocurrent on the photon energy can be well
accounted for by assuming a plane wave for the final state. However, the
experimental data, both for the highest occupied and the lowest unoccupied
molecular orbital of PTCDA, exhibits an additional modulation attributed to final
state scattering effects. Nevertheless, as these effects beyond a plane wave
final state are comparably small, we are able, with extrapolations beyond the
attainable photon energy range, to reconstruct three-dimensional images for both
orbitals in agreement with calculations for the adsorbed molecule.
PMID- 26437299
TI - Continuous Fabrication of Hierarchical and Asymmetric Bijel Microparticles,
Fibers, and Membranes by Solvent Transfer-Induced Phase Separation (STRIPS).
AB - Continuous generation of hierarchical and asymmetric bijels based on solvent
transfer-induced phase separation (STRIPS) is demonstrated. In STRIPS, phase
separation is induced by solvent extraction from an initially homogeneous ternary
mixture, and bicontinuous morphology is stabilized by inter-facial attachment of
nano-particles, which are functionalized in situ. STRIPS allows stable bijel
formation from a wide variety of liquids and particles.
PMID- 26437296
TI - A mechanical argument for the differential performance of coronary artery grafts.
AB - Coronary artery bypass grafting (CABG) acutely disturbs the homeostatic state of
the transplanted vessel making retention of graft patency dependent on chronic
remodeling processes. The time course and extent to which remodeling restores
vessel homeostasis will depend, in part, on the nature and magnitude of the
mechanical disturbances induced upon transplantation. In this investigation,
biaxial mechanical testing and histology were performed on the porcine left
anterior descending artery (LAD) and analogs of common autografts, including the
internal thoracic artery (ITA), radial artery (RA), great saphenous vein (GSV)
and lateral saphenous vein (LSV). Experimental data were used to quantify the
parameters of a structure-based constitutive model enabling prediction of the
acute vessel mechanical response pre-transplantation and under coronary loading
conditions. A novel metric Xi was developed to quantify mechanical differences
between each graft vessel in situ and the LAD in situ, while a second metric
Omega compares the graft vessels in situ to their state under coronary loading.
The relative values of these metrics among candidate autograft sources are
consistent with vessel-specific variations in CABG clinical success rates with
the ITA as the superior and GSV the inferior graft choices based on mechanical
performance. This approach can be used to evaluate other candidate tissues for
grafting or to aid in the development of synthetic and tissue engineered
alternatives.
PMID- 26437300
TI - Differential senescence capacities in meibomian gland carcinoma and basal cell
carcinoma.
AB - Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid
carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses.
We address here the question of the differential mechanisms between these two
eyelid cancers that explain their different outcome. A total of 102 confirmed MGC
and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty
diagnosed BCC cases were collected to determine the telomere length, the presence
of senescent cells, and the expression levels of the telomere capping shelterin
complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the
shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as
well as mutations in P53 were detected both in MGC and BCC. It suggests that the
decreased protein levels of the shelterin complex and the shortened telomere
length contribute to the tumorigenesis of MGC and BCC. However, several
parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin
subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly
mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples
contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were
lower in BCC. These results support a model where a preserved P53 checkpoint in
BCC leads to cellular senescence and reduced tumor proliferation as compared to
MGC.
PMID- 26437301
TI - Foot placement control and gait instability among people with stroke.
AB - Gait instability is a common problem following stroke, as evidenced by increases
in fall risk and fear of falling. However, the mechanism underlying gait
instability is currently unclear. We recently found that young, healthy humans
use a consistent gait stabilization strategy of actively controlling their
mediolateral foot placement based on the concurrent mechanical state of the
stance limb. In the present work, we tested whether people with stroke (n = 16)
and age-matched controls (n = 19) used this neuromechanical strategy.
Specifically, we used multiple linear regressions to test whether (1) swing phase
gluteus medius (GM) activity was influenced by the simultaneous state of the
stance limb and (2) mediolateral foot placement location was influenced by swing
phase GM activity and the mechanical state of the swing limb at the start of the
step. We found that both age-matched controls and people with stroke classified
as having a low fall risk (Dynamic Gait Index [DGI] score >19) essentially used
the stabilization strategy previously described in young controls. In contrast,
this strategy was disrupted for people with stroke classified as higher fall risk
(DGI =19), particularly for steps taken with the paretic limb. These results
suggest that a reduced ability to appropriately control foot placement may
contribute to poststroke instability.
PMID- 26437303
TI - Chronic Constriction Injury of the Rat's Infraorbital Nerve (IoN-CCI) to Study
Trigeminal Neuropathic Pain.
AB - Animal models are important tools to study the pathophysiology and pharmacology
of neuropathic pain. This manuscript describes the surgical and behavioral
procedures to study trigeminal neuropathic pain in rats. To meet the specificity
of trigeminal neuropathic pain syndromes, the infraorbital nerve (IoN) is
subjected to a chronic constriction injury (CCI) by loosely ligating the nerve.
An intra-orbital approach is presented here to expose and ligate the IoN in the
orbital cavity. After IoN ligation, rats exhibit changes in spontaneous behavior
and in response to von Frey hair stimulation that are indicative of persistent
pain and mechanical allodynia. Two phases can be defined in the development of
the behavioral changes. During the first week following IoN-CCI (phase 1), rats
show an increased and asymmetric face grooming activity, i.e., with face wash
strokes primarily directed to the nerve-injured IoN territory. A distinction is
made between face grooming behavior that is part of a more general body grooming
behavior, which remains largely unaffected by IoN-CCI, and face grooming that is
neither preceded nor followed by body grooming, which is significantly increased
after IoN-CCI. During this period, responsiveness to mechanical stimulation of
the IoN territory is reduced. This hyporesponsiveness is abruptly replaced by an
extreme hyperresponsiveness whereby even very weak stimulus intensities provoke
nocifensive behavior (phase 2). The phenomenological similarities between these
behavioral alterations and reported signs of facial pain (i.e., responses to
noxious stimulation of the face) suggest the presence of dysesthesia/paresthesia
and mechanical allodynia in the ligated IoN territory.
PMID- 26437304
TI - Brain Proteomics.
PMID- 26437302
TI - A Lentiviral Vector Expressing Japanese Encephalitis Virus-like Particles Elicits
Broad Neutralizing Antibody Response in Pigs.
AB - BACKGROUND: Japanese encephalitis virus (JEV) is the major cause of viral
encephalitis in Southeast Asia. Vaccination of domestic pigs has been suggested
as a "one health" strategy to reduce viral disease transmission to humans. The
efficiency of two lentiviral TRIP/JEV vectors expressing the JEV envelope prM and
E glycoproteins at eliciting protective humoral response was assessed in a mouse
model and piglets. METHODOLOGY/PRINCIPAL FINDINGS: A gene encoding the envelope
proteins prM and E from a genotype 3 JEV strain was inserted into a lentiviral
TRIP vector. Two lentiviral vectors TRIP/JEV were generated, each expressing the
prM signal peptide followed by the prM protein and the E glycoprotein, the latter
being expressed either in its native form or lacking its two C-terminal
transmembrane domains. In vitro transduction of cells with the TRIP/JEV vector
expressing the native prM and E resulted in the efficient secretion of virus-like
particles of Japanese encephalitis virus. Immunization of BALB/c mice with
TRIP/JEV vectors resulted in the production of IgGs against Japanese encephalitis
virus, and the injection of a second dose one month after the prime injection
greatly boosted antibody titers. The TRIP/JEV vectors elicited neutralizing
antibodies against JEV strains belonging to genotypes 1, 3, and 5. Immunization
of piglets with two doses of the lentiviral vector expressing JEV virus-like
particles led to high titers of anti-JEV antibodies, that had efficient
neutralizing activity regardless of the JEV genotype tested.
CONCLUSIONS/SIGNIFICANCE: Immunization of pigs with the lentiviral vector
expressing JEV virus-like particles is particularly efficient to prime antigen
specific humoral immunity and trigger neutralizing antibody responses against JEV
genotypes 1, 3, and 5. The titers of neutralizing antibodies elicited by the
TRIP/JEV vector are sufficient to confer protection in domestic pigs against
different genotypes of JEV and this could be of a great utility in endemic
regions where more than one genotype is circulating.
PMID- 26437308
TI - Self-Passivation of Defects: Effects of High-Energy Particle Irradiation on the
Elastic Modulus of Multilayer Graphene.
AB - The elastic modulus of multilayer graphene is found to be more robust to damage
created by high-energy alpha-particle irradiation as compared to monolayer
graphene. Theoretical analysis indicates that irradiation of multilayer graphene
generates interlayer links that potentially increase the stiffness of the
multilayer by passivating local defects.
PMID- 26437309
TI - An exceptionally long CA-repeat in the core promoter of SCGB2B2 links with the
evolution of apes and Old World monkeys.
AB - We have recently reported a genome-scale catalog of human protein-coding genes
that contain "exceptionally long" STRs (>=6-repeats) in their core promoter,
which may be of selective advantage in this species. At the top of that list,
SCGB2B2 (also known as SCGBL), contains one of the longest CA-repeat STRs
identified in a human gene core promoter, at 25-repeats. In the study reported
here, we analyzed the conservation status of this CA-STR across evolution. The
functional implication of this STR to alter gene expression activity was also
analyzed in the HEK-293 cell line. We report that the SCGB2B2 core promoter CA
repeat reaches exceptional lengths, ranging from 9- to 25-repeats, across Apes
(Hominoids) and the Old World monkeys (CA>2-repeats were not detected in any
other species). The longest CA-repeats and highest identity in the SCGB2B2
protein sequence were observed between human and bonobo. A trend for increased
gene expression activity was observed from the shorter to the longer CA-repeats
(p<0.009), and the CA-repeat increased gene expression activity, per se (p<0.02).
We propose that the SCGB2B2 gene core promoter CA-repeat functions as an
expression code for the evolution of Apes and the Old World monkeys.
PMID- 26437310
TI - Drugs, Substance Use Disorder and Driving: Intervention of Health Professionals
in the Treatment of Addictions.
AB - Editorial of vol 27-3.
PMID- 26437311
TI - A group intervention to reduce intimate partner violence among female drug users.
Results from a randomized controlled pilot trial in a community substance-abuse
center.
AB - BACKGROUND: A greater proportion of drug dependent women are victims of intimate
partner violence (IPV) than women in the general population; however, few
interventions have been developed to reduce IPV among drug dependent women.
METHODS: An adapted version of the Women's Wellness Treatment, to address IPV and
depressive symptoms, was piloted in a randomized controlled trial conducted in
outpatient treatment program in Barcelona, Spain among 14 women receiving
outpatient treatment for a drug use disorder who screened positive for IPV in the
previous month. Participants were randomly assigned to receive the 10 session
cognitive behavioral therapy (IPaViT-CBT) group intervention or treatment as
usual. The frequency of IPV, depressive symptoms, substance use, quality of life
and health status were assessed at baseline and 1, 3 and 12 months post
intervention. Intention to treat analysis was performed. RESULTS: Moderate
effects for the intervention were found in reducing psychological maltreatment,
increasing assertiveness of IPV and reducing aggressiveness in the partner
relationship, and in reducing the frequency of drinking up to 3 months post
intervention. The intervention did not significantly reduce the likelihood of any
IPV, depressive symptoms, quality of life or self-reported health status, up to
12-months post intervention. CONCLUSION: This pilot trial suggests some initial
support for the 10-session CBT group intervention among IPV victims who received
treatment for drug use. Study findings indicate that it is feasible to deliver
the intervention in a community substance abuse center. An adequately powered
trial is required to replicate these results.
PMID- 26437312
TI - Management of opioid-dependent patients: comparison of the cost associated with
use of buprenorphine/naloxone or methadone, and their interactions with
concomitant treatments for infectious or psychiatric comorbidities.
AB - The objective was to estimate the annual interaction management cost of agonist
opioid treatment (AOT) for opioid-dependent (OD) patients with buprenorphine
naloxone (Suboxone(r)) (B/N) or methadone associated with concomitant treatments
for infectious (HIV) or psychiatric comorbidities. A costs analysis model was
developed to calculate the associated cost of AOT and interaction management. The
AOT cost included pharmaceutical costs, drug preparation, distribution and
dispensing, based on intake regimen (healthcare center or take-home) and type and
frequency of dispensing (healthcare center or pharmacy), and medical visits. The
cost of methadone also included single-dose bottles, monthly costs of custody at
pharmacy, urine toxicology drug screenings and nursing visits. Potential
interactions between AOT and concomitant treatments (antivirals,
antibacterials/antifungals, antipsychotics, anxiolytics, antidepressant and
anticonvulsants), were identified to determine the additional use of healthcare
resources for each interaction management. The annual cost per patient of AOT was
?1,525.97 for B/N and ?1,467.29 for methadone. The average annual cost per
patient of interaction management was ?257.07 (infectious comorbidities), ?114.03
(psychiatric comorbidities) and ?185.55 (double comorbidity) with methadone and
?7.90 with B/N in psychiatric comorbidities. Total annual costs of B/N were
?1,525.97, ?1,533.87 and ?1,533.87 compared to ?1,724.35, ?1,581.32 and ?1,652.84
for methadone per patient with infectious, psychiatric or double comorbidity
respectively.Compared to methadone, the total cost per patient with OD was lower
with B/N (?47.45-?198.38 per year). This is due to the differences in interaction
management costs associated with the concomitant treatment of infectious and/or
psychiatric comorbidities.
PMID- 26437313
TI - Online Gambling Advertising Regulations in Spain. A Study on the Protection of
Minors.
AB - This article examines the online gambling advertising regulations in Spain
currently in effect to assess the actual protection of underage youth. In recent
years, online gambling among youth has increased. Through advertising, online
gambling companies incite and encourage an involvement that can be harmful for
vulnerable audiences. Some studies have demonstrated that advertising influences
youths' assessment of gambling by increasing its appeal. We demonstrate that the
shortcomings of the legal framework in force results in effective vulnerability
of minors. We claim that society should seek to implement a regulatory framework
to protect children from the risk of developing an addiction.
PMID- 26437314
TI - Polydrug use and its relationship with the familiar and social context amongst
young college students.
AB - The prevalence of polydrug use continues to grow among Spanish college students.
The European Observatory for Drugs and Addictions establishes three different
types of polydrug use: Pattern A (consumers of alcohol and tobacco), Pattern B
(consumers of cannabis plus alcohol and/or tobacco) and Pattern C (consumers of
cannabis plus alcohol plus tobacco plus at least one other kind of illegal drug).
The objectives are: 1) to study the frequency of substance consumption among a
sample of young Spanish undergradudates studying health and sports science
according to their sex; 2) to describe the patterns of polydrug use; 3) to study
the relationship between the polydrug use of the participants and polydrug use
within their closest environment (parents, sisters or brothers, best friend and
partner). The sample was composed of 480 Spanish undergraduates (43.7% females)
aged 18 to 36. The level of drug consumption of students and their closest
reference persons was evaluated by means of a self-report measure. A total of 46%
of the participants reported consumption of two or more substances; among them
29.4% corresponded to Pattern A, 50.7% to Pattern B and 16.7% to Pattern C, while
3.2% corresponded to other multiple consumption patterns (alcohol + cocaine;
alcohol + cocaine + tobacco; alcohol + inhalants; amphetamines + hallucinogens +
Spice). An important correlation was observed concerning polydrug use between
participants and their closest reference persons: the more the reference person
is a multiple consumer, the more the participant tends to consume. Polydrug use
within the closest environment emerges as one of the key elements to be taken
into account in further prevention programs.
PMID- 26437315
TI - Opioid Receptor Antagonists in the Treatment of Alcoholism.
AB - OBJECTIVES: On the basis of the recent advances in drug therapy of alcoholism, we
conducted a review on opioid receptor antagonist drugs with approved indication
for the treatment of alcoholism, such as naltrexone and nalmefene. METHODS: We
reviewed over 100 publications on peptides and opioid receptors, as well as
studies conducted in experimental animals and in humans on the effect of opioid
receptor antagonists on alcohol consumption in the treatment of alcoholism. We
also reviewed the pharmacological characteristics of naltrexone and nalmefene,
and the usefulness of these drugs in clinical practice. RESULTS: Much evidence
has demonstrated the efficacy of naltrexone and nalmefene for the reduction of
alcohol consumption, in experimental animals as well as in humans examined under
experimental bar conditions; however, due to its different receptor profile,
nalmefene has been associated with higher efficacy levels in reducing alcohol
consumption in alcohol-dependent rats. In addition, a great number of controlled
clinical trials have demonstrated the efficacy of naltrexone for relapse
prevention in patients with an alcohol dependence disorder. Recent controlled
clinical trials have demonstrated the efficacy of nalmefene "as-needed" in the
reduction of alcohol consumption in subjects with mild alcohol dependence.
CONCLUSIONS: Both naltrexone and nalmefene have proved to be safe, well
tolerated, easy to manage, and efficient drugs for the treatment of alcohol
dependence disorder (currently known as alcohol use disorder). On the basis of
recent controlled clinical trials, nalmefene has been shown to result in a
significant reduction of alcohol consumption, thereby representing a new
objective that extends the therapeutic possibilities for those patients who do
not wish for a continuous abstinence, but rather a reduction of alcohol
consumption.
PMID- 26437316
TI - New Psychoactive Drugs.
PMID- 26437317
TI - Alcohol consumption in college students from the pharmacy faculty.
AB - Alcohol consumption is highly prevalent in university students. Early detection
in future health professionals is important: their consumption might not only
influence their own health but may determine how they deal with the
implementation of preventive strategies in the future. The aim of this paper is
to detect the prevalence of risky alcohol consumption in first- and last-degree
year students and to compare their drinking patterns.Risky drinking in pharmacy
students (n=434) was assessed and measured with the AUDIT questionnaire (Alcohol
Use Disorders Identification Test). A comparative analysis between college
students from the first and fifth years of the degree in pharmacy, and that of a
group of professors was carried to see differences in their alcohol intake
patterns.Risky drinking was detected in 31.3% of students. The highest prevalence
of risky drinkers, and the total score of the AUDIT test was found in students in
their first academic year. Students in the first academic level taking morning
classes had a two-fold risk of risky drinking (OR=1.9 (IC 95%1.1-3.1)) compared
with students in the fifth level. The frequency of alcohol consumption increases
with the academic level, whereas the number of alcohol beverages per drinking
occasion falls.Risky drinking is high during the first year of university. As
alcohol consumption might decrease with age, it is important to design preventive
strategies that will strengthen this tendency.
PMID- 26437319
TI - No Time to Wait.
PMID- 26437318
TI - HPV Prevalence in Multiple Anatomical Sites among Men Who Have Sex with Men in
Peru.
AB - BACKGROUND: Human Papilloma Virus (HPV) infection is the most common sexually
transmitted viral infection worldwide. HPV is highly prevalent in sexually active
men who have sex with men (MSM) and has been associated with anal cancer, penile
cancer, and oropharyngeal cancer. METHODS: From March to September 2011, we
conducted a cross-sectional study of HPV prevalence among MSM above age 18 years.
Participants were recruited using respondent driven sampling at Clinica Cayetano
Heredia. All participants provided anal, genital, and oral samples for HPV DNA
testing, and blood for HIV and HPV antibody testing. RESULTS: A total of 200 MSM
were recruited in the study. The mean age was 34 years (range 18-59 years, SD =
9.4) and101 participants were HIV negative (99 HIV positive). HPV 6/11/16/18 or
quadrivalent HPV vaccine (HPV4) genotype seroprevalence among HIV negative and
positive MSM was 64.3% (55%-75.9%) and 93.8% (87.6%-99.2%) respectively
(p<0.001). HIV positivity was associated with a higher prevalence of HPV4 and HPV
16/18 DNA at external genital sites and the anal canal. HPV4 DNA prevalence at
external genital sites among HIV negative and positive MSM was 14.9% and 28.7% (p
= 0.02) respectively, at anal canal was 50.9% and 79.0% (p = 0.001), and at the
oral cavity was 9.9% and 8.5% (p = 0.6). CONCLUSIONS: HPV4 seroprevalence was
high in our study among both HIV positives and negatives, with HPV DNA prevalence
much lower, and the anal canal being the anatomical site with the highest HPV DNA
prevalence. HPV prevention interventions are needed among MSM at high-risk for
HIV infection.
PMID- 26437320
TI - Anti-inflammatory Effects of Clostridial Collagenase Results from In Vitro and
Clinical Studies.
AB - BACKGROUND: Digestion of collagen with clostridial collagenase (CC) produces
peptides that can induce cellular responses consistent with wound healing in
vivo. However, nonhealing human wounds are typically in a state of chronic
inflammation. We evaluated the effects of CC on markers of inflammation in cell
culture and wound fluid from diabetic patients. METHODS: Lipopolysaccharide
induced release of tumor necrosis factor-alpha and interleukin-6 from interferon
gamma-activated THP-1 monocytes was measured in the presence or absence of CC or
CC collagen digests. In the clinical study, 17 individuals with mildly inflamed
diabetic foot ulcers were randomized to receive CC ointment (CCO) or hydrogel.
Weekly assessments included wound appearance and measurements. Wound exudate was
collected at baseline and at 2 and 4 weeks of treatment. A multiplex assay was
used to measure levels of analytes, including those associated with inflammation
and with inflammation resolution. RESULTS: Lower levels of tumor necrosis factor
alpha and interleukin-6 were found in media of cells cultured with CC or CC
digests of collagen type I or III than for untreated lipopolysaccharide controls
(P < .05). Clinically, CCO and hydrogel resulted in improvement in wound
appearance and a decrease in mean wound area. The CCO, but not the hydrogel, was
found to increase the level of analytes associated with resolution of
inflammation while decreasing those associated with inflammation. There was a
general correlation between resolution of inflammation and healing. CONCLUSIONS:
These results support a hypothesis that debridement with CCO is associated with
decreased inflammation and greater progress toward healing.
PMID- 26437321
TI - Correction: Characterization of Carriage Isolates of Neisseria meningitidis in
the Adolescents and Young Adults Population of Bogota (Colombia).
PMID- 26437324
TI - Docetaxel rechallenge in metastatic castration-resistant prostate cancer: any
place in the modern treatment scenario? An intention to treat evaluation.
AB - BACKGROUND: We evaluated the possible advantages of a docetaxel (DCT) rechallenge
strategy in metastatic castration-resistant prostate cancer (mCRPC) patients,
also given the possible earlier positioning of this treatment option in the
modern scenario. PATIENTS & METHODS: All mCRPC patients planned for DCT
chemotherapy rechallenge in our institutions were evaluated. RESULTS: Of 128
patients, 98 achieved disease control on the initial DCT round. After a treatment
holiday of 8.3 months, the 98 responsive patients underwent a second DCT round,
with 56 cases achieving again disease control. After a 5.7-month off-treatment
period, 32 of these cases underwent a third DCT round, and 16 responded. Lastly,
after a further 4.2-month treatment holiday, eight patients underwent a fourth
DCT round and two responded. Median time to definitive disease progression for
the whole population was 16.4 months. CONCLUSIONS: Rechallenge with DCT may be
considered a suitable treatment option for mCRPC patients recurring after a
successful DCT chemotherapy. The interest in this strategy may be increased
because of the showed efficacy of early DCT chemotherapy in patients with bulky
disease (CHAARTED study) and the potential lower efficacy of the new hormonal
agents abiraterone acetate and enzalutamide when used in a immediate sequencing.
PMID- 26437325
TI - Preparation of a Superhydrophobic and Peroxidase-like Activity Array Chip for
H2O2 Sensing by Surface-Enhanced Raman Scattering.
AB - In this paper, we propose a novel and simple method for preparing a dual
biomimetic functional array possessing both superhydrophobic and peroxidase-like
activity that can be used for hydrogen peroxide (H2O2) sensing. The proposed
method is an integration innovation that combines the above two properties and
surface-enhanced Raman scattering (SERS). We integrated a series of well-ordered
arrays of Au points (d = 1 mm) onto a superhydrophobic copper (Cu)/silver (Ag)
surface by replicating an arrayed molybdenum template. Instead of using
photoresists and the traditional lithography method, we utilized a chemical
etching method (a substitution reaction between Cu and HAuCl4) with a Cu/Ag
superhydrophobic surface as the barrier layer, which has the benefit of water
repellency. The as-prepared Au points were observed to possess peroxidase-like
activity, allowing for catalytic oxidation of the chromogenic molecule o
phenylenediamine dihydrochloride (OPD). Oxidation was evidenced by a color change
in the presence of H2O2, which allows the array chip to act as an H2O2 sensor. In
this study, the water repellency of the superhydrophobic surface was used to
fabricate the array chip and increase the local reactant concentration during the
catalytic reaction. As a result, the catalytic reaction occurred when only 2 MUL
of an aqueous sample (OPD/H2O2) was placed onto the Au point, and the enzymatic
product, 2,3-diaminophenazine, showed a SERS signal distinguishable from that of
OPD after mixing with 2 MUL of colloidal Au. Using the dual-biomimetic functional
array chip, quantitative analysis of H2O2 was performed by observing the change
in the SERS spectra, which showed a concentration-dependent behavior for H2O2.
This method allows for the detection of H2O2 at concentrations as low as 3 pmol
per 2 MUL of sample, which is a considerable advantage in H2O2 analysis. The as
prepared substrate was convenient for H2O2 detection because only a small amount
of sample was required in each analysis. Highly sensitive detection was realized
using SERS. Therefore, this chip was shown to exhibit significant potential for
applications in bioanalysis.
PMID- 26437326
TI - En Bloc Multivisceral and Kidney Transplantation in an HIV Patient: First Case
Report.
AB - The continual improvement in outcome with highly active antiretroviral therapy
(HAART) for human immunodeficiency virus (HIV) infection and visceral
transplantation for gut failure stimulated our interest in lifting HIV infection
as a contraindication for intestinal and multivisceral transplantation. This
report is the first to describe visceral transplantation in a patient with HIV
infection. A HAART regimen was introduced in the setting of short-gut syndrome
with successful suppression of HIV viral load. The indication for en bloc
multivisceral and kidney transplantation was end-stage liver failure with
portomesenteric venous thrombosis and chronic renal insufficiency. The underlying
hepatic pathology was alcoholic and home parenteral nutrition-associated
cirrhosis. Surgery was complicated due to technical difficulties with excessive
blood loss and long operative time. The complex posttransplant course included
multiple exploratory laparotomies due to serious intra-abdominal and systemic
infections. Heavy immunosuppression was required to treat recurrent episodes of
severe allograft rejection. Posttransplant oral HAART successfully sustained
undetectable viral load. Unfortunately, the patient succumbed to sepsis 3 months
posttransplant. With new insights into the biology of gut immunity, mechanisms of
allograft tolerance, and HIV-associated immune dysregulation, successful outcome
is anticipated, particularly in patients who are in need of isolated intestinal
and less-organ-contained visceral allografts.
PMID- 26437327
TI - Rooting depth, water relations and non-structural carbohydrate dynamics in three
woody angiosperms differentially affected by an extreme summer drought.
AB - In 2012, an extreme summer drought induced species-specific die-back in woody
species in Northeastern Italy. Quercus pubescens and Ostrya carpinifolia were
heavily impacted, while Prunus mahaleb was largely unaffected. By comparing
seasonal changes in isotopic composition of xylem sap, rainfall and deep soil
samples, we show that P. mahaleb has a deeper root system than the other two
species. This morphological trait allowed P mahaleb to maintain higher water
potential (Psi), gas exchange rates and non-structural carbohydrates content
(NSC) throughout the summer, when compared with the other species. More
favourable water and carbon states allowed relatively stable maintenance of stem
hydraulic conductivity (k) throughout the growing season. In contrast, in Quercus
pubescens and Ostrya carpinifolia, decreasing Psi and NSC were associated with
significant hydraulic failure, with spring-to-summer k loss averaging 60%. Our
data support the hypothesis that drought-induced tree decline is a complex
phenomenon that cannot be modelled on the basis of single predictors of tree
status like hydraulic efficiency, vulnerability and carbohydrate content. Our
data highlight the role of rooting depth in seasonal progression of water status,
gas exchange and NSC, with possible consequences for energy-demanding mechanisms
involved in the maintenance of vascular integrity.
PMID- 26437328
TI - [Comparison of the Biochemical Recurrence risk between Radical Prostatectomy and
Brachytherapy in the treatment of low- and intermediate-risk prostate cancer].
AB - OBJECTIVES: To evaluate the results of patients treated with Radical
Prostatectomy (RP) and Brachytherapy for low- and intermediate-risk localized
prostate cancer and to determine the Biochemical Recurrence (BCR) risk according
to the treatment performed. METHODS: The study included 129 patients treated with
iodine-125 seeds Brachytherapy, 98 patients treated with Laparoscopic RP (LRP),
and 61 patients treated with Robotic RP (RRP) at our institution between December
1999 and January 2010, who had a low-risk disease according to D'Amico criteria
(PSA <10 ng/mL, Gleason < or = 6, cT1c-T2a), or an intermediate-risk disease (PSA
= or >10 and < 20 ng/mL, Gleason = 7, cT2b), but with a tumor burden of up to
30%. Follow-up was conducted with PSA at 1, 3, and 6 months, and then every six
months. As for Brachytherapy, annual digital rectal examinations were also
performed. A PSA level increase of 2 ng/mL above the nadir in Brachytherapy
(confirmed in 2 cases) and a PSA value greater than 0.2 ng/mL after RP were
considered BCR. RESULTS: Overall mean follow-up was 60.5 months (R:1-152), with a
mean time for BCR of 51.7 months (R:1-138). Estimated 5-year Biochemical
Recurrence-free Survival (BCRFS) in patients with D'Amico low-risk was 85.7%,
77.2% and 90.7% (p 0.336), while for intermediate-risk it was 75.8%, 68.1% and
65.1% (p 0.114), for Brachytherapy, LRP and RRP respectively. In the univariate
analysis, the Gleason score 7, a clinical stage T2b, and a D'Amico intermediate
risk were associated with an increased BCR risk, and treatment with Brachytherapy
was associated with a decreased BCR risk, all these being statistically
significant. In the multivariate analysis, only the Gleason score 7 was
significant; treatment with LRP, RRP or Brachytherapy was not associated with a
greater BCR risk. CONCLUSION: Brachytherapy and Laparoscopic or Robotic Radical
Prostatectomy showed no difference in terms of Biochemical Recurrence risk in
patients treated for low-risk or intermediate-risk tumors, with low tumor volume.
PMID- 26437329
TI - [Optimization and improvement of surgical indicators in the urology department of
a regional hospital of the ministry of health of the Junta de Andalucia].
AB - OBJECTIVES: To improve the rates of surgical activity and average waiting times
for surgery, and to optimize the number of surgical indications in the Urology
Department of a Regional Hospital. METHODS: A study and analysis of the surgical
activity and different indexes in 2014 was performed comparing the first half of
the year and the second half after implementation of improvement measures. STUDY
VARIABLES: operating room occupancy rate, average hospital stay, cancellations,
surgical complexity, average number of surgeries per operative room, average
global waiting time and waiting time by 120 and 180 days guarantee decrees
following the Junta de Andalucia standards. RESULTS: In comparison with the first
half of 2014, in the second half the operating room occupancy rate increased from
79% to 85%, the average stay decreased from 6 to 3 days, and a decrease in
cancellations from 9% to 6% was observed. Moreover, a decrease in the mean
waiting times was observed for surgeries subject to both the 120 days and 180
days guarantee decree and a decrease in the number of surgical indications in
urology through the implementation of protocols based on clinical practice
guidelines. CONCLUSIONS: Despite the limitations of the study, and being a small
Department in a district hospital, we observed that optimization of resources,
implementation of protocols, and clinical pathways can improve and optimize
different indicators of surgical activity.
PMID- 26437331
TI - [Testicular epidermoid cyst: A rare entity].
AB - OBJECTIVE: Testicular epidermoid cyst is a rare clinical entity that accounts for
1% of testicular neoplasias. METHODS AND RESULTS: We report two cases of
testicular epidermoid cysts in a 18 and 19 year old males with a painless
testicular lesion. Testicular US was carried out showing a hypoechoic nodule in
both cases. With the suspicion of testicular neoplasm inguinal orchiectomy was
carried out with placement of testicular prostheses in the same act. The
pathology report was testicular epidermoid cyst in both cases. CONCLUSIONS:
Testicular epidermoid cysts are an uncommon benign entity. When there is a
suspicion of this diagnosis, based on tumor markers and ultrasound or MRI images,
testicular parenchyma-sparing surgery must be attempted.
PMID- 26437330
TI - Thermochemotherapy in adjuvant treatment of primary high risk non muscle invasive
bladder cancers: Single center results.
AB - OBJECTIVE: To evaluate the results of Thermochemotherapy in adjuvant treatment of
primary high risk non-muscle invasive bladder cancer in our center. METHODS: The
study included 26 patients with an age of 51-78 years (mean: 62.4 years). All
patients had transurethral tumor resection (TURB) after being diagnosed with a
primary bladder tumor and were pathologically diagnosed with non-muscle invasive
urothelial carcinoma. Thermochemotherapy (TCT) applications were performed via
the Synergo(r) system SB-TS 101. RESULTS: Of the study participants, 13 patients
had T1 Grade III, six patients had T1Grade III CIS (+), four patients had Ta
Grade III, and three patients Ta Grade II multiple > 5 cm tumor. In all patients,
six weeks plus six months protocol were completed. All patients completed the
follow-up protocol. With a median follow-up time of 16.4 months (range: 6 - 48
months), recurrent urothelial carcinoma was identified in three patients. With a
median follow-up time of 16.4 months, the recurrence-free survival was 88.4% in
26 patients included in the study. CONCLUSIONS: The obtained data suggest that
the TCT method can be used effectively and safely in non-muscle invasive bladder
cancers of primary high-risk. Prospective randomized studies will shed light on
this subject which are BCG vs TCT in primary high risk patients and second course
BCG vs TCT in the BCG insufficient patients.
PMID- 26437332
TI - [Prostate Specific Antigen (PSA) use in a national health department].
AB - OBJECTIVES: PSA is a frequently used marker in the daily clinical practice for
the diagnosis and management of prostate cancer. We analysed the use of PSA in
our health department in patients with and without prostate cancer diagnosis.
METHODS: The registry of all PSA petitions in our health department during 2011
and 2012 was used. Demographic data were used to establish each year's population
and the data corresponding to the prevalence of prostate cancer patients,
performing a descriptive study. Thus, the use of PSA in patients with or without
prostate cancer was studied. RESULTS: 25.700 PSA petitions are issued annually in
our department over a total of 67.000 males older than 45. This entails a cost of
332.815 Euros annually. Within the group of patients with no prostate cancer
diagnosis, it was noticed that the percentage of individuals with at least one
annual PSA petition per decade of age is of 23% in males in their fifties, 40% in
their sixties, 46% in their seventies, and 36% in their eighties or successive
decades. Furthermore, in these cancer-free patients, around 3.800 annual
petitions fall on individuals over 75 and with PSA under 4 ng/ml, from which 20%
are repeated petitions over the same individual in the same year. Over 1100 males
under 45 have an annual PSA. Regarding the average PSA value for decade of age in
cancer-free patients, it is of 0.89 +/- 0.4 ng/ml in the forties decade, 1.26 +/-
1.07 ng/ml in the fifties, 1.67 +/- 1.38 ng/ml in the sixties, 1.96 +/- 1.78
ng/ml in the seventies, and 2.24 +/- 2.16 ng/ml in the eighties. We ascertained,
also, that for every 144 PSA petitions one prostate cancer case is diagnosed.
Regarding the use of this marker in cancer patients, 1.800 petitions are destined
to patients follow up annually, and over 200 fall on the newly diagnosed cases.
CONCLUSIONS: Even though annually less than 50% of males get PSA petitions in any
decade of age, its use is sometimes incorrect, including repeated petitions in a
short period of time or in individuals of extreme age.
PMID- 26437333
TI - [Metastatic urinary bladder involvement in breast cancer].
AB - OBJECTIVE: To contribute to the literature with three unusual cases of primary
breast tumor with metastasis to the urinary bladder. METHODS: Presentation of the
three clinical cases and bibliographic review. RESULTS: Three women, with an
average age of 49.3 years, were diagnosed with invasive lobular breast carcinoma.
Two of them suffered from hematuria after being diagnosed with breast cancer. The
third patient was diagnosed incidentally after a routine CT scan. Upon diagnosis
of the bladder metastases, they already had metastasis in other locations. The
treatment of the three cases was palliative. The cause of death was due to
additional pathologies. CONCLUSIONS: The presence of bladder metastases due to
breast cancer is infrequent. The appearance of urinary tract symptoms in these
patients requires a diagnostic study in order to rule out metastases.
PMID- 26437334
TI - An Aquatic Microbial Metaproteomics Workflow: From Cells to Tryptic Peptides
Suitable for Tandem Mass Spectrometry-based Analysis.
AB - Meta-omic technologies such as metagenomics, metatranscriptomics and
metaproteomics can aid in the understanding of microbial community structure and
metabolism. Although powerful, metagenomics alone can only elucidate functional
potential. On the other hand, metaproteomics enables the description of the
expressed in situ metabolism and function of a community. Here we describe a
protocol for cell lysis, protein and DNA isolation, as well as peptide digestion
and extraction from marine microbial cells collected on a cartridge filter unit
(such as the Sterivex filter unit) and preserved in an RNA stabilization solution
(like RNAlater). In mass spectrometry-based proteomics studies, the
identification of peptides and proteins is performed by comparing peptide tandem
mass spectra to a database of translated nucleotide sequences. Including the
metagenome of a sample in the search database increases the number of peptides
and proteins that can be identified from the mass spectra. Hence, in this
protocol DNA is isolated from the same filter, which can be used subsequently for
metagenomic analysis.
PMID- 26437335
TI - A Hybrid CPU/GPU Pattern-Matching Algorithm for Deep Packet Inspection.
AB - The large quantities of data now being transferred via high-speed networks have
made deep packet inspection indispensable for security purposes. Scalable and low
cost signature-based network intrusion detection systems have been developed for
deep packet inspection for various software platforms. Traditional approaches
that only involve central processing units (CPUs) are now considered inadequate
in terms of inspection speed. Graphic processing units (GPUs) have superior
parallel processing power, but transmission bottlenecks can reduce optimal GPU
efficiency. In this paper we describe our proposal for a hybrid CPU/GPU pattern
matching algorithm (HPMA) that divides and distributes the packet-inspecting
workload between a CPU and GPU. All packets are initially inspected by the CPU
and filtered using a simple pre-filtering algorithm, and packets that might
contain malicious content are sent to the GPU for further inspection. Test
results indicate that in terms of random payload traffic, the matching speed of
our proposed algorithm was 3.4 times and 2.7 times faster than those of the AC
CPU and AC-GPU algorithms, respectively. Further, HPMA achieved higher energy
efficiency than the other tested algorithms.
PMID- 26437336
TI - Continued pregnancy and vaginal delivery after 32 weeks of gestation for
monoamniotic twins.
AB - OBJECTIVE: To report the outcomes of 38 monoamniotic twin pregnancies managed
homogeneously to assess whether continuing the pregnancy past 32 weeks of
gestation and vaginal delivery are reasonable options. STUDY DESIGN: Single
centre retrospective study including all monoamniotic pregnancies managed over a
20-year period at Port-Royal Obstetrics Department, Paris, France. METHODS: In
the study department, both continuation of the pregnancy up to 36 weeks of
gestation and vaginal delivery are allowed for monoamniotic pregnancies in some
conditions. Perinatal outcomes are described and then compared according to mode
of delivery for patients who gave birth at or after 32 weeks of gestation.
RESULTS: Three of the 38 pregnancies included fetal malformations; in two of
these cases, both fetuses died in utero at 26 weeks of gestation. In cases
without malformations, one twin died in utero in two women at 28.0 and 29.2 weeks
of gestation, and both fetuses died in two other women at 24.0 and 24.5 weeks of
gestation. Mean gestational age at delivery was 32.9 weeks (range 24.0-36.3).
Five women gave birth between 22 and 26 weeks of gestation, six women gave birth
between 27 and 31 weeks of gestation, and 27 women gave birth at or after 32
weeks of gestation (26 after excluding those with fetal malformations). No
intrauterine or neonatal deaths were observed at or after 32 weeks of gestation.
The 28 infants delivered vaginally did not differ significantly from the 22
infants born by caesarean section in terms of umbilical artery pH or 5-min Apgar
scores. CONCLUSION: Continuation of monoamniotic pregnancies beyond 32 weeks of
gestation and trial of vaginal delivery are both reasonable options if the
parents agree, and optimal surveillance is provided.
PMID- 26437337
TI - Detection of Candida spp. in the vagina of a cohort of nulliparous pregnant women
by culture and molecular methods: Is there an association between maternal
vaginal and infant oral colonisation?
AB - BACKGROUND: Most studies describing vaginal Candida spp. in pregnancy focus on
symptomatic vaginitis, rather than asymptomatic colonisation, and solely utilise
microbiological culture. The extent to which asymptomatic vaginal carriage may
represent a reservoir for infant oral colonisation has been highly debated.
MATERIALS AND METHODS: This study formed part of the Candida and Staphylococcus
Transmission Longitudinal Evaluation (CASTLE) study, in Melbourne, Australia,
from 2009 to 2011 and used culture and molecular methods to examine vaginal swabs
collected late in the third trimester of pregnancy for Candida spp. Oral swabs
from infants were also examined using culture methods. RESULTS: Overall, 80 of
356 (22%) women were positive for Candida spp; the majority being Candida
albicans (83%). Candida glabrata and other Candida spp. were also identified, but
in much lower numbers. Molecular analysis identified numerous positive samples
not detected by culture, including 13 cases of C. albicans. In addition, some
positive samples only recorded to genus level by culture were accurately
identified as either C. albicans or C. glabrata following molecular analyses.
Eighteen infants recorded positive Candida spp. cultures, predominantly C.
albicans. However, there were only four (25%) mother/infant dyads where C.
albicans was detected. CONCLUSIONS: This study provides valuable data on
asymptomatic colonisation rates of Candida spp. within an asymptomatic population
of women late in pregnancy. The utilisation of molecular methods improved the
rate of detection and provided a more accurate means for identification of non
albicans Candida spp. The low mother/infant colonisation rate suggests that non
maternal sources are likely involved in determining infant oral colonisation
status.
PMID- 26437338
TI - lncRScan-SVM: A Tool for Predicting Long Non-Coding RNAs Using Support Vector
Machine.
AB - Functional long non-coding RNAs (lncRNAs) have been bringing novel insight into
biological study, however it is still not trivial to accurately distinguish the
lncRNA transcripts (LNCTs) from the protein coding ones (PCTs). As various
information and data about lncRNAs are preserved by previous studies, it is
appealing to develop novel methods to identify the lncRNAs more accurately. Our
method lncRScan-SVM aims at classifying PCTs and LNCTs using support vector
machine (SVM). The gold-standard datasets for lncRScan-SVM model training, lncRNA
prediction and method comparison were constructed according to the GENCODE gene
annotations of human and mouse respectively. By integrating features derived from
gene structure, transcript sequence, potential codon sequence and conservation,
lncRScan-SVM outperforms other approaches, which is evaluated by several criteria
such as sensitivity, specificity, accuracy, Matthews correlation coefficient
(MCC) and area under curve (AUC). In addition, several known human lncRNA
datasets were assessed using lncRScan-SVM. LncRScan-SVM is an efficient tool for
predicting the lncRNAs, and it is quite useful for current lncRNA study.
PMID- 26437340
TI - Spatial and temporal relationships among watershed mining, water quality, and
freshwater mussel status in an eastern USA river.
AB - The Powell River of southwestern Virginia and northeastern Tennessee, USA, drains
a watershed with extensive coal surface mining, and it hosts exceptional
biological richness, including at-risk species of freshwater mussels, downstream
of mining-disturbed watershed areas. We investigated spatial and temporal
patterns of watershed mining disturbance; their relationship to water quality
change in the section of the river that connects mining areas to mussel habitat;
and relationships of mining-related water constituents to measures of recent and
past mussel status. Freshwater mussels in the Powell River have experienced
significant declines over the past 3.5 decades. Over that same period, surface
coal mining has influenced the watershed. Water-monitoring data collected by
state and federal agencies demonstrate that dissolved solids and associated
constituents that are commonly influenced by Appalachian mining (specific
conductance, pH, hardness and sulfates) have experienced increasing temporal
trends from the 1960s through ~2008; but, of those constituents, only dissolved
solids concentrations are available widely within the Powell River since ~2008.
Dissolved solids concentrations have stabilized in recent years. Dissolved
solids, specific conductance, pH, and sulfates also exhibited spatial patterns
that are consistent with dilution of mining influence with increasing distance
from mined areas. Freshwater mussel status indicators are correlated negatively
with dissolved solids concentrations, spatially and temporally, but the direct
causal mechanisms responsible for mussel declines remain unknown.
PMID- 26437339
TI - Down-Regulation of miR-92 in Breast Epithelial Cells and in Normal but Not Tumour
Fibroblasts Contributes to Breast Carcinogenesis.
AB - BACKGROUND: MicroRNA (miR) expression is commonly dysregulated in many cancers,
including breast. MiR-92 is one of six miRs encoded by the miR-17-92 cluster, one
of the best-characterised oncogenic miR clusters. We examined expression of miR
92 in the breast epithelium and stroma during breast cancer progression. We also
investigated the role of miR-92 in fibroblasts in vitro and showed that down
regulation in normal fibroblasts enhances the invasion of breast cancer
epithelial cells. METHODOLOGY/PRINCIPAL FINDINGS: We used laser microdissection
(LMD) to isolate epithelial cells from matched normal, DCIS and invasive tissue
from 9 breast cancer patients and analysed miR-92 expression by qRT-PCR.
Expression of ERbeta1, a direct miR-92 target, was concurrently analysed for each
case by immunohistochemistry. LMD was also used to isolate matched normal (NFs)
and cancer-associated fibroblasts (CAFs) from 14 further cases. Effects of miR-92
inhibition in fibroblasts on epithelial cell invasion in vitro was examined using
a MatrigelTM assay. miR-92 levels decreased in microdissected epithelial cells
during breast cancer progression with highest levels in normal breast epithelium,
decreasing in DCIS (p<0.01) and being lowest in invasive breast tissue (p<0.01).
This was accompanied by a shift in cell localisation of ERbeta1 from nuclear
expression in normal breast epithelium to increased cytoplasmic expression during
progression to DCIS (p = 0.0078) and invasive breast cancer (p = 0.031). ERbeta1
immunoreactivity was also seen in stromal fibroblasts in tissues. Where miR-92
expression was low in microdissected NFs this increased in matched CAFs; a trend
also seen in cultured primary fibroblasts. Down-regulation of miR-92 levels in
NFs but not CAFs enhanced invasion of both MCF-7 and MDA-MB-231 breast cancer
epithelial cells. CONCLUSIONS: miR-92 is gradually lost in breast epithelial
cells during cancer progression correlating with a shift in ERbeta1
immunoreactivity from nuclei to the cytoplasm. Our data support a functional role
in fibroblasts where modification of miR-92 expression can influence the invasive
capacity of breast cancer epithelial cells. However in silico analysis suggests
that ERbeta1 may not be the most important miR-92 target in breast cancer.
PMID- 26437341
TI - De-oiled two-phase olive mill waste may reduce water contamination by metribuzin.
AB - The impact of de-oiled two-phase olive mill waste (DW) on the behavior of
metribuzin in Mediterranean agricultural soils is evaluated, and the effects of
the transformation of organic matter from this waste under field conditions are
assessed. Four soils were selected and amended in the laboratory with DW at the
rates of 2.5% and 5%. One of these soils was also amended in the field with 27
and 54 Mg ha(-1) of DW for 9 years. Significant increases in metribuzin sorption
were observed in all the amended soils. In the laboratory, the 5% DW application
rate increased the t1/2 values of metribuzin from 22.9, 35.8, 29.1, and 20.0 d
for the original soils to 59.2, 51.1, 45.7, and 29.4d, respectively. This was
attributable mainly to the inhibitory effect of the amendment on microbial
activity. However, the addition of DW transformed naturally under field
conditions decreased the persistence down to 3.93 d at the greater application
rate. Both amendments (fresh and field-aged DW) significantly reduced the amount
of metribuzin leached. This study showed that DW amendment may be an effective
and sustainable management practice for controlling groundwater contamination by
metribuzin.
PMID- 26437343
TI - Origin of high ammonium, arsenic and boron concentrations in the proximity of a
mine: Natural vs. anthropogenic processes.
AB - High ammonium (NH4), arsenic (As) and boron (B) concentrations are found in
aquifers worldwide and are often related to human activities. However, natural
processes can also lead to groundwater quality problems. High NH4, As and B
concentrations have been identified in the confined, deep portion of the Niebla
Posadas aquifer, which is near the Cobre Las Cruces (CLC) mining complex. The
mine has implemented a Drainage and Reinjection System comprising two rings of
wells around the open pit mine, were the internal ring drains and the external
ring is used for water reinjection into the aquifer. Differentiating geogenic and
anthropogenic sources and processes is therefore crucial to ensuring good
management of groundwater in this sensitive area where groundwater is extensively
used for agriculture, industry, mining and human supply. No NH4, As and B are
found in the recharge area, but their concentrations increase with depth,
salinity and residence time of water in the aquifer. The increased salinity down
flow is interpreted as the result of natural mixing between infiltrated meteoric
water and the remains of connate waters (up to 8%) trapped within the pores.
Ammonium and boron are interpreted as the result of marine solid organic matter
degradation by the sulfate dissolved in the recharge water. The light
delta(15)NNH4 values confirm that its origin is linked to marine organic matter.
High arsenic concentrations in groundwater are interpreted as being derived from
reductive dissolution of As-bearing goethite by dissolved organic matter. The
lack of correlation between dissolved Fe and As is explained by the massive
precipitation of siderite, which is abundantly found in the mineralization.
Therefore, the presence of high arsenic, ammonium and boron concentrations is
attributed to natural processes. Ammonium, arsenic, boron and salinity define
three zones of groundwater quality: the first zone is close to the recharge area
and contains water of sufficient quality for human drinking; the second zone is
downflow and contains groundwater suitable for continuous irrigation but not
drinkable due to high ammonium concentrations; and the third zone contains
groundwater of elevated salinity (up to 5940 MUS cm(-1)) and is not useable due
to high ammonium, arsenic and boron concentrations.
PMID- 26437344
TI - Distribution of virulence factors in ESBL-producing Escherichia coli isolated
from the environment, livestock, food and humans.
AB - In this study, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli
isolates recovered from the following sources were characterized with regard to
the occurrence and distribution of uropathogenic and enteric pathogenic virulence
factors: surface waters (rivers and lakes, n=60), the intestines of freshwater
fish (n=33), fresh vegetables (n=26), retail poultry meat (n=13) and the fecal
samples of livestock (n=28), healthy humans (n=34) and primary care patients
(n=13). Among the 207 isolates, 82% tested positive by PCR for one or more of the
virulence factors (VF) that predict uropathogenicity, TraT, fyuA, chuA, PAI, yfcv
or vat. Uropathogenic E. coli (UPEC) were detected in each of the analyzed
sources. Regarding virulence factors for intestinal pathogenic E. coli, these
were found more rarely and predominantly associated with the aquatic environment,
with aagR (EAEC) found in isolates from surface waters and STp (porcine heat
stable enterotoxin) and LT (heat-labile enterotoxin) associated with isolates
from fish. Aggregate VF scores (the number of unique virulence factors detected
for each isolate) were lowest among isolates belonging to phylogenetic group B1
and highest among group B2. Clustering of the isolates by phylogenetic group,
multilocus sequence type (MLST) and ESBL-types revealed clonal overlaps of
A:ST10(CTX-M-1) and D:ST350(CTX-M-1) between the sources of livestock, poultry
meat and healthy humans, suggesting livestock, in particular poultry, represents
a potential reservoir for these particular UPEC clones. The clones A:ST10(CTX-M
55) and B2:ST131(CTX-M-27), harboring uropathogenic virulence factors were
significantly associated with fresh vegetables and with fish, respectively.
Further clonal complexes with source overlaps included D:ST38(CTX-M-14),
D:ST69(CTX-M-15), D:ST405(CTX-M-15) and D:ST648(CTX-M-15), which were found in
surface water and healthy humans. Identifying potential reservoirs of UPEC in the
environment, animals, food and humans is important in order to assess routes of
transmission and risk factors for acquiring UPEC.
PMID- 26437345
TI - Cooling and eutrophication of southern Chilean lakes.
AB - Understanding the impacts of global warming and human-disturbances on lakes is
required for implementing management strategies aimed at mitigating the decline
of the quality and availability of water for humans. We assessed temporal trends
in water parameters, and the contribution of land use to the eutrophication of
the largest lakes of central-southern Chile. The mean values of water parameters
varied seasonally, with lakes Chapo and Caburgua exhibiting lower pH,
temperature, and N/P ratio values. Over the assessed period (19 years), we found
a temporal reduction in water conductivity and temperature of the lakes. The
concentration of NO3(-)-N, PO4(3-)-P and dissolved oxygen increased in all the
lakes, but pH increased in eight out of the ten lakes. The negative temporal
trend in temperature was more pronounced as the depth level increased. Lakes
whose basins had a higher percentage of forest plantation and urban areas had
larger values of Chlorophyll a and pH, as well as, smaller values of dissolved
oxygen. Lakes whose basins included larger percentages of native forest had
smaller nutrient (NO3(-)-N, PO4(3-)-P) concentrations. Our findings suggest that
decreased rainfall in central-southern Chile due to climate change may cause a
decrease of particulate material that is carried by tributaries into the lakes.
The observed temporal decrease in temperature, especially at the deeper levels,
may be explained by the rapid melting of glaciers. Although the studied lakes are
classified as oligotrophic, deforestation and expansion of urban areas around the
lakes have led to increased nutrient input, thus accelerating their
eutrophication.
PMID- 26437342
TI - Environmental exposure to manganese in air: Associations with tremor and motor
function.
AB - BACKGROUND: Manganese (Mn) inhalation has been associated with neuropsychological
and neurological sequelae in exposed workers. Few environmental epidemiologic
studies have examined the potentially neurotoxic effects of Mn exposure in
ambient air on motor function and hand tremor in adult community residents. Mn
exposed residents were recruited in two Ohio towns: Marietta, a town near a ferro
manganese smelter, and East Liverpool, a town adjacent to a facility processing,
crushing, screening, and packaging Mn products. METHODS: Chronic (>= 10 years)
exposure to ambient air Mn in adult residents and effects on neuropsychological
and neurological outcomes were investigated. Participants from Marietta (n=100)
and East Liverpool (n=86) were combined for analyses. AERMOD dispersion modeling
of fixed-site outdoor air monitoring data estimated Mn inhalation over a ten year
period. Adult Mn-exposed residents' psychomotor ability was assessed using Finger
Tapping, Hand Dynamometer, Grooved Pegboard, and the Computerized Adaptive
Testing System (CATSYS) Tremor system. Bayesian structural equation modeling was
used to assess associations between air-Mn and motor function and tremor.
RESULTS: Air-Mn exposure was significantly correlated in bivariate analyses with
the tremor test (CATSYS) for intensity, center frequency and harmonic index. The
Bayesian path analysis model showed associations of air-Mn with the CATSYS non
dominant center frequency and harmonic index; while the Bayesian structural
equation model revealed associations between air-Mn and lower Finger Tapping
scores. Household income was significantly associated with motor dysfunction but
not with tremor. CONCLUSION: Tremor and motor function were associated with
higher exposure to airborne Mn.
PMID- 26437346
TI - Direct and indirect effects of an invasive omnivore crayfish on leaf litter
decomposition.
AB - Invasive alien species (IAS) can disrupt important ecological functions in
aquatic ecosystems; however, many of these effects are not quantified and remain
speculative. In this study, we assessed the effects of the invasive crayfish
Procambarus clarkii (Girard, 1852) on leaf litter decomposition (a key ecosystem
process) and associated invertebrates using laboratory and field manipulative
experiments. The crayfish had significant impacts on leaf decomposition due to
direct consumption of leaf litter and production of fine particulate organic
matter, and indirectly due to consumption of invertebrate shredders. The
invertebrate community did not appear to recognize P. clarkii as a predator, at
least in the first stages after its introduction in the system; but this
situation might change with time. Overall, results suggested that the omnivore
invader P. clarkii has the potential to affect detritus-based food webs through
consumption of basal resources (leaf litter) and/or consumers. Recognizing that
this IAS is widespread in Europe, Asia and Africa, and may attain high density
and biomass in aquatic ecosystems, our results are important to develop
strategies for improving stream ecosystem functioning and to support management
actions aiming to control the invasive omnivore P. clarkii.
PMID- 26437347
TI - An epidemiological assessment of stomatal ozone flux-based critical levels for
visible ozone injury in Southern European forests.
AB - Southern forests are at the highest ozone (O3) risk in Europe where ground-level
O3 is a pressing sanitary problem for ecosystem health. Exposure-based standards
for protecting vegetation are not representative of actual field conditions. A
biologically-sound stomatal flux-based standard has been proposed, although
critical levels for protection still need to be validated. This innovative
epidemiological assessment of forest responses to O3 was carried out in 54 plots
in Southeastern France and Northwestern Italy in 2012 and 2013. Three O3 indices,
namely the accumulated exposure AOT40, and the accumulated stomatal flux with and
without an hourly threshold of uptake (POD1 and POD0) were compared. Stomatal O3
fluxes were modeled (DO3SE) and correlated to measured forest-response
indicators, i.e. crown defoliation, crown discoloration and visible foliar O3
injury. Soil water content, a key variable affecting the severity of visible
foliar O3 injury, was included in DO3SE. Based on flux-effect relationships, we
developed species-specific flux-based critical levels (CLef) for forest
protection against visible O3 injury. For O3 sensitive conifers, CLef of 19 mmol
m(-2) for Pinus cembra (high O3 sensitivity) and 32 mmol m(-2) for Pinus
halepensis (moderate O3 sensitivity) were calculated. For broadleaved species, we
obtained a CLef of 25 mmol m(-2) for Fagus sylvatica (moderate O3 sensitivity)
and of 19 mmol m(-2) for Fraxinus excelsior (high O3 sensitivity). We showed that
an assessment based on PODY and on real plant symptoms is more appropriated than
the concentration-based method. Indeed, POD0 was better correlated with visible
foliar O3 injury than AOT40, whereas AOT40 was better correlated with crown
discoloration and defoliation (aspecific indicators). To avoid an underestimation
of the real O3 uptake, we recommend the use of POD0 calculated for hours with a
non-null global radiation over the 24-h O3 accumulation window.
PMID- 26437348
TI - Impact of biosolids and wastewater effluent application to agricultural land on
corticosterone content in lettuce plants.
AB - We studied corticosterone occurrence in lettuce plants grown on three biosolids
amended soils under irrigation with either tap water or secondary wastewater
effluent. Corticosterone was examined as it has possible implications for human
health. It is a major glucocorticoid, and as such has an effect on regulation of
metabolism, immune functions and stress response. The plants were grown in 220-L
lysimeters packed with 3 soils which represent a wide range of physicochemical
properties. Lettuce was grown in cycles (two in summer and two in winter) during
3 years, and in every spring season the sludges were re-applied. Corticosterone
was quantified using ELISA and LCMS, and was found in the biosolids, tap water,
wastewater effluent and lettuce plants. The respective ranges of concentrations
were: 11-92 ng g(-1), 0.5-1.6 ng L(-1), 4.2-4.7 ng L(-1); and 1-900 ng g(-1) dry
weight. A positive relationship was found between corticosterone concentrations
in winter-grown lettuces and the plants fresh weight. The corticosterone content
of the plants did not correspond with either the type of irrigation water or the
biosolids type and rate of application or the soil properties.
PMID- 26437349
TI - Maize yield gaps caused by non-controllable, agronomic, and socioeconomic factors
in a changing climate of Northeast China.
AB - Closing the gap between current and potential yields is one means of increasing
agricultural production to feed the globally increasing population. Therefore,
investigation of the geographic patterns, trends and causes of crop yield gaps is
essential to identifying where yields might be increased and quantifying the
contributions of yield-limiting factors that may provide us potentials to enhance
crop productivity. In this study, the changes in potential yields, attainable
yields, potential farmers' yields, and actual farmers' yields during the past
five decades in Northeast China (NEC) were investigated. Additionally the yield
gaps caused by non-controllable, agronomic, and socioeconomic factors were
determined. Over the period 1961 to 2010 the estimated regional area-weighted
mean maize potential yield, attainable yield, and potential farmers' yield were
approximately 12.3 t ha(-1), 11.5 t ha(-1), and 6.4 t ha(-1) which showed a
decreasing tendency. The actual farmers' yield over NEC was 4.5 t ha(-1), and
showed a tendency to increase (p<0.01) by 1.27 t ha(-1) per decade. The regional
mean total yield gap (YGt), weighted by the area in each county dedicated to
maize crop, was 64% of potential yield. Moreover, 8, 40, and 16% reductions in
potential yields were due to non-controllable factors (YGI), agronomic factors
(YGII), and socioeconomic factors (YGIII), respectively. Therefore, the
exploitable yield gap, considered here as the difference between the potential
yield and what one can expect considering non-controllable factors (i.e. YGt
YGI), of maize in NEC was about 56%. The regional area-weighted averages of YGt,
and YGIII were found to have significant decreases of 11.0, and 10.7% per decade.
At the time horizon 2010, the exploitable yield gaps were estimated to equal 36%
of potential yield. This led to the conclusion that the yield gap could be deeply
reduced by improving local agronomic management and controlling socioeconomic
factors.
PMID- 26437350
TI - Carbon based secondary compounds do not provide protection against heavy metal
road pollutants in epiphytic macrolichens.
AB - Lichens are useful monitoring organisms for heavy metal pollution. They are high
in carbon based secondary compounds (CBSCs) among which some may chelate heavy
metals and thus increase metal accumulation. This study quantifies CBSCs in four
epiphytic lichens transplanted for 6months on stands along transects from a
highway in southern Norway to search for relationships between concentrations of
heavy metals and CBSCs along a gradient in heavy metal pollutants. Viability
parameters and concentrations of 21 elements including nutrients and heavy metals
in these lichen samples were reported in a separate paper. Medullary CBSCs in
fruticose lichens (Ramalina farinacea, Usnea dasypoga) were reduced in the most
polluted sites, but not in foliose ones (Parmelia sulcata, Lobaria pulmonaria),
whereas cortical CBSC did not change with distance from the road in any species.
Strong positive correlations only occurred between the major medullary compound
stictic acid present in L. pulmonaria and most heavy metals, consistent with a
chelating role of stictic acid, but not of other studied CBSCs or in other
species. However, heavy metal chelating did not protect L. pulmonaria against
damage because this species experienced the strongest reduction in viability in
the polluted sites. CBSCs with an accumulation potential for heavy metals should
be quantified in lichen biomonitoring studies of heavy metals because they, like
stictic acid, could overshadow pollutant inputs in some species rendering
biomonitoring data less useful. In the two fruticose lichen species, CBSCs
decreased with increasing heavy metal concentration, probably because heavy metal
exposure impaired secondary metabolism. Thus, we found no support for a heavy
metal protection role of any CBSCs in studied epiphytic lichens. No intraspecific
relationships occurred between CBSCs versus N or C/N-ratio. Interspecifically,
medullary CBSCs decreased and cortical CBSCs increased with increasing C/N-ratio.
PMID- 26437351
TI - Nitrate source identification in groundwater of multiple land-use areas by
combining isotopes and multivariate statistical analysis: A case study of Asopos
basin (Central Greece).
AB - Nitrate (NO3) is one of the most common contaminants in aquatic environments and
groundwater. Nitrate concentrations and environmental isotope data (delta(15)N
NO3 and delta(18)O-NO3) from groundwater of Asopos basin, which has different
land-use types, i.e., a large number of industries (e.g., textile, metal
processing, food, fertilizers, paint), urban and agricultural areas and livestock
breeding facilities, were analyzed to identify the nitrate sources of water
contamination and N-biogeochemical transformations. A Bayesian isotope mixing
model (SIAR) and multivariate statistical analysis of hydrochemical data were
used to estimate the proportional contribution of different NO3 sources and to
identify the dominant factors controlling the nitrate content of the groundwater
in the region. The comparison of SIAR and Principal Component Analysis showed
that wastes originating from urban and industrial zones of the basin are mainly
responsible for nitrate contamination of groundwater in these areas. Agricultural
fertilizers and manure likely contribute to groundwater contamination away from
urban fabric and industrial land-use areas. Soil contribution to nitrate
contamination due to organic matter is higher in the south-western part of the
area far from the industries and the urban settlements. The present study aims to
highlight the use of environmental isotopes combined with multivariate
statistical analysis in locating sources of nitrate contamination in groundwater
leading to a more effective planning of environmental measures and remediation
strategies in river basins and water bodies as defined by the European Water
Frame Directive (Directive 2000/60/EC).
PMID- 26437352
TI - Performance evaluation of conventional and water saving taps.
AB - The rapid pace of urbanisation comes with considerable environmental implications
including pressures on already stressed limited water resources. In urban areas,
most of the water use is associated with water consumption in buildings. The
second largest use of water is via taps. It is often assumed that water taps with
low flow rates can contribute to reduced per capita water consumption. However,
this is based on very little evidence. This paper presents the synthesis of a
13,000 high resolution observations made to investigate the actual water
consumption of innovative (water saving) electronic taps and conventional mixer
taps. High resolution flow-meters and data loggers were fitted into two washrooms
in two different buildings of a higher education institution to record the water
use through the basin taps. The recorded data provided information on duration,
frequency of use and volume of water consumption per use. The data was helpful in
identifying trends in hot and cold water use and therefore can be useful in
estimating energy for producing hot water and associated greenhouse gas
emissions. Analysis of the observed data suggests that the low flow taps have
greater mean water consumption per event than the conventional taps and water
consumption is more influenced by user behaviour rather than the technology.
PMID- 26437353
TI - Risk assessment of down-the-drain chemicals at large spatial scales: Model
development and application to contaminants originating from urban areas in the
Saint Lawrence River Basin.
AB - Chemicals released into freshwater systems threaten ecological functioning and
may put aquatic life and the health of humans at risk. We developed a new
contaminant fate model (CFM) that follows simple, well-established methodologies
and is unique in its cross-border, seamless hydrological and geospatial
framework, including lake routing, a critical component in northern environments.
We validated the model using the pharmaceutical Carbamazepine and predicted eco
toxicological risk for 15 pharmaceuticals in the Saint-Lawrence River Basin,
Canada. The results indicated negligible to low environmental risk for the
majority of tested chemicals, while two pharmaceuticals showed elevated risk in
up to 13% of rivers affected by municipal effluents. As an integrated model, our
CFM is designed for application at very large scales with the primary goal of
detecting high risk zones. In regulatory frameworks, it can help screen existing
or new chemicals entering the market regarding their potential impact on human
and environmental health. Due to its high geospatial resolution, our CFM can also
facilitate the prioritization of actions, such as identifying regions where
reducing contamination sources or upgrading treatment plants is most pertinent to
achieve targeted pollutant removal or to protect drinking water resources.
PMID- 26437354
TI - Analysis of the effects of meteorology on aircraft exhaust dispersion and
deposition using a Lagrangian particle model.
AB - The risk of air quality degradation is of considerable concern particularly for
those airports that are located near urban areas. The ability to quantitatively
predict the effects of air pollutants originated by airport operations is
important for assessing air quality and the related impacts on human health.
Current emission regulations have focused on local air quality in the proximity
of airports. However, an integrated study should consider the effects of
meteorological events, at both regional and local level, that can affect the
dispersion and the deposition of exhausts. Rigorous scientific studies and
extensive experimental data could contribute to the analysis of the impacts of
airports expansion plans. This paper is focused on the analysis of the effects of
meteorology on aircraft emission for the Marco Polo Airport in Venice. This is
the most important international airport in the eastern part of the Po' Valley,
one of the most polluted area in Europe. Air pollution is exacerbated by
meteorology that is a combination of large and local scale effects that do not
allow significant dispersion. Moreover, the airport is located near Venice, a
city of noteworthy cultural and architectural relevance, and nearby the lagoon
that hosts several areas of outstanding ecological importance at European level
(Natura 2000 sites). Dispersion and deposit of the main aircraft exhausts (NOx,
HC and CO) have been evaluated by using a Lagrangian particle model. Spatial and
temporal aircraft exhaust dispersion has been analyzed for LTO cycle. Aircraft
taxiing resulted to be the most impacting aircraft operation especially for the
airport working area and its surroundings, however occasionally peaks may be
observed even at high altitudes when cruise mode starts. Mixing height can affect
concentrations more significantly than the concentrations in the exhausts
themselves. An increase of HC and CO concentrations (15-50%) has been observed
during specific meteorological events.
PMID- 26437355
TI - Cadmium and phosphate variability during algal blooms of the dinoflagellate
Lingulodinium polyedrum in Todos Santos Bay, Baja California, Mexico.
AB - Dinoflagellate algal blooms (DABs), with Lingulodinium polyedrum as the dominant
species, have increased over the past few years in coastal areas off Baja
California, Mexico. Vertical and temporal variability of particulate cadmium
(Cdp), dissolved Cd (Cdd), PO4(3-) and Cdd/PO4(3-) were investigated during two
intense DABs of L. polyedrum that occurred during the fall of 2011 and 2012 in
Todos Santos Bay. Results were then, compared with data gathered in the absence
of algal blooms during the autumn of 2013. In both algal blooms, L. polyedrum
tended to be concentrated near the surface throughout the duration; however,
during DAB 2011 the number of cells was twice as abundant ([10.0 +/- 8.0] * 10(5)
cells L(-1)) as in DAB 2012 ([5.0 +/- 4.4] * 10(5) cells L(-1)). During DAB 2011,
Cdp increased significantly (up to 1.02 +/- 0.99 nmol kg(-1)) and was positively
correlated with the cell abundance of L. polyedrum, suggesting that this
dinoflagellate is able to assimilate and concentrate Cdd. Likewise, Cdd (up to
0.71 +/- 0.17 nM) increased in the days of highest cell abundance, which could be
attributed to uptake and subsequent regeneration of Cdd resulting from the
remineralization of organic particulate matter produced during the bloom, as well
as with the presence of organic ligands secreted by L. polyedrum that could keep
Cdd in solution. During DAB 2011, dissolved Cdd/PO4(3-) ratios exhibited high
vertical and temporal variability in the upper 5 m of the water column, but
remained virtually constant near the bottom, suggesting a depth-dependent
decoupling between these two dissolved components during the bloom development.
Given the observed differences in the vertical and temporal variability of Cdd,
Cdp, and PO4(3-) between these two intense DABs, we propose the existence of an
abundance threshold of approximately 10(6) cells L(-1) of L. polyedrum above
which Cd and PO4(3-) significantly increased due to remineralization in coastal
waters during the bloom development.
PMID- 26437356
TI - The influence of environmental and physiological factors on the litter size of
wild boar (Sus scrofa) in an agriculture dominated area in Germany.
AB - The wild boar population has increased enormously in all of Europe over the last
decades and caused problems like crop damage, transmission of diseases, and
vehicle accidents. Therefore, it is necessary to investigate the underlying
causes of this increase in order to be able to manage populations effectively.
The purpose of this study was to analyse how environmental (food and climate) and
physiological factors (maternal weight and age) as well as hunting and population
density influence the litter size of wild boar populations in Northern Germany.
The mean litter size in the studied population for the whole period was 6.6
(range 1-12), which is one of the highest in all of Europe. Litter size was
positively influenced by maternal body weight, higher mast yield of oak as well
as higher temperature in combination with higher precipitation in summer. Only
higher temperature or only higher precipitation in summer however had a negative
effect on litter size production. Probably,weather and food conditions act via
maternal bodyweight on the litter size variation in wild boar. Hunting as well a
s population density did not affect the litter size variation in this study which
might indicate that wild boar population did not reach carrying capacity yet.
PMID- 26437357
TI - Reconstruction of centennial-scale fluxes of chemical elements in the Australian
coastal environment using seagrass archives.
AB - The study of a Posidonia australis sedimentary archive has provided a record of
changes in element concentrations (Al, Fe, Mn, Pb, Zn, Cr, Cd, Co, As, Cu, Ni and
S) over the last 3000 years in the Australian marine environment. Human-derived
contamination in Oyster Harbor (SW Australia) started ~100 years ago (AD ~1900)
and exponentially increased until present. This appears to be related to European
colonization of Australia and the subsequent impact of human activities, namely
mining, coal and metal production, and extensive agriculture. Two contamination
periods of different magnitude have been identified: Expansion period (EXP, AD
~1900-1970) and Establishment period (EST, AD ~1970 to present). Enrichments of
chemical elements with respect to baseline concentrations (in samples older than
~115 cal years BP) were found for all elements studied in both periods, except
for Ni, As and S. The highest enrichment factors were obtained for the EST period
(ranging from 1.3-fold increase in Cu to 7.2-fold in Zn concentrations) compared
to the EXP period (1.1-fold increase for Cu and Cr to 2.4-fold increase for Pb).
Zinc, Pb, Mn and Co concentrations during both periods were 2- to 7-fold higher
than baseline levels. This study demonstrates the value of Posidonia mats as long
term archives of element concentrations and trends in coastal ecosystems. We also
provide preliminary evidence on the potential for Posidonia meadows to act as
significant long-term biogeochemical sinks of chemical elements.
PMID- 26437358
TI - Examining within-person and between-person effects of victimization and social
risk on cannabis use among emerging adults in substance-use treatment.
AB - The goals of this study were to examine associations between within- and between
person social risk and victimization and cannabis use among emerging adults in
substance-use treatment. We also tested gender differences for both victimization
and social risk. Participants consisted of 3,052 emerging adults (M(age) = 20.0
years; SD = 2.21) entering substance-use treatment in a wide range of treatment
centers across the United States. Individuals were assessed on all measures at
baseline 3, 6, and 12 months. We fitted a taxonomy of multilevel growth curve
models to test main effects, and interactive relations between within- and
between-person social risk, victimization, and gender on cannabis use. Several
significant interactions were evident. Irrespective of gender, within-person
increases in social risk were associated with contemporaneous increases in
cannabis use; however, the magnitude of this relation was comparatively more
pronounced for men. Similar gender differences emerged between individuals. Males
experiencing heightened social risk over time tended to show high levels of early
cannabis use. Simple slope analyses revealed that reporting more (+1 SD) social
risk than one's own mean resulted in significant increases in cannabis use for
both men and women. Cross-level simple slope analyses revealed no differences in
cannabis use among individuals reporting low (-1 SD) social risk and
victimization, but significant increases in cannabis use for individuals
reporting high (+ 1 SD) victimization and social risk. Results demonstrate
support for gender differences in social risk on cannabis use and the importance
of considering within-person effects. (PsycINFO Database Record
PMID- 26437360
TI - Islands contribute disproportionately high amounts of evolutionary diversity in
passerine birds.
AB - Island systems generally have fewer species than continental areas due to their
small size and geographical isolation. Low island diversity reduces the
possibility of exportation of island lineages and island systems are not thought
to have a major influence on the build-up of continental diversity. However, the
view that islands represent the end of the colonization road has recently been
challenged and islands do represent the origin of some specific continental
lineages. Here we assess the net contribution of island systems to global
diversity patterns of passerine birds, using a complete phylogeny (5,949
species), biogeographical regionalization and null-model comparisons. We show
that, in contrast to major continental regions, island regions export relatively
more evolutionary lineages than would be expected based on current distributional
patterns. This result challenges a central paradigm in island biogeography and
changes our perception of the relative importance of islands for the build-up of
global diversity.
PMID- 26437359
TI - Change over time in adolescent and friend alcohol use: Differential associations
for youth with and without childhood attention-deficit/hyperactivity disorder
(ADHD).
AB - Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased
risk for experiencing alcohol-related problems by adulthood. However, few studies
have examined contextual factors that may contribute to this risk. The current
study examined 1 widely investigated social-contextual risk factor, friend
alcohol use, in a sample of adolescents with and without a history of ADHD. One
hundred and 59 adolescents (14-17 years old) with childhood ADHD and 117
demographically similar youth without ADHD were interviewed annually in the
Pittsburgh ADHD Longitudinal Study. Adolescents reported the frequency of their
own alcohol use in the prior 12 months and the number of friends who used alcohol
regularly or occasionally (perceived friend alcohol use). Multiple-group parallel
process models indicated that increases in friend alcohol use were more strongly
associated with increases in adolescent alcohol use over time for individuals
with ADHD (r = .15, SE = 0.04; 95% confidence interval [CI] = [0.08, 0.22]) than
for those without ADHD (r = .06, SE = 0.03; 95% CI [0.00, 0.11]). These results
suggest that social factors are an important part of escalating alcohol use among
adolescents with ADHD histories, and they highlight the possibility that
interventions focused on the peer context could be important for these at-risk
youth. Additional social network research on adolescent alcohol use within the
larger context of other relationships (e.g., family and romantic relationships)
is indicated.
PMID- 26437361
TI - Quantifying Neonicotinoid Insecticide Residues Escaping during Maize Planting
with Vacuum Planters.
AB - Neonicotinoid residues escaping in vacuum-planter exhaust during maize planting
were measured in 25 fields in southwestern Ontario in 2013-2014 using filter bags
to collect planter exhaust dust and horizontal and vertical sticky traps to
collect planter operation-generated dust. Atrazine residues were used to
differentiate between neonicotinoid residues originating from seed or from
disturbed soil. Recovery rates of seed-applied neonicotinoids in exhaust were
0.014 and 0.365% in 2013 and 2014, respectively, calculated on the basis of
neonicotinoid concentrations in preplant soil and seed application rates.
Neonicotinoid exhaust emission rates were 0.0036 and 0.1104 g/ha for 2013 and
2014, respectively, with 99.9472 and 99.7820% originating from treated seed in
2013 and 2014, respectively, calculated on the basis of the atrazine marker.
Rates of recovery of seed-applied neonicotinoid residues by exhaust filter bags
were 0.015 and 0.437% for 2013 and 2014, respectively. Neonicotinoid residues
captured on horizontal and vertical traps were 1.10 ng/cm2 (0.1104 g/ha) and 1.45
ng/cm2 (0.0029 g/ha), respectively, with 92.31 and 93.03% originating from
treated seed, respectively, representing 0.3896% of the original active
ingredient applied to the seed planted. Exposure to pollinators can be best
reduced by strategies to keep active ingredient on the seed, below the soil
surface, and in the field where applied.
PMID- 26437362
TI - Enantioselective 1,2-Difunctionalization of Dienes Enabled by Chiral Palladium
Complex-Catalyzed Cascade Arylation/Allylic Alkylation Reaction.
AB - A Pd-catalyzed highly enantioselective three-component coupling of 1,3-dienes
with aryl iodines and sodium dialkyl malonates has been successfully established
by using a H8-BINOL-based phosphoramidite ligand. This reaction proceeded via a
Pd-catalyzed cascade arylation and asymmetric allylic alkylation reaction,
providing an efficient strategy for the enantioselective 1,2-difunctionalization
of 1,3-dienes.
PMID- 26437363
TI - Mitoepigenetics: The different shades of grey.
AB - Epigenetic modifications of the nuclear genome have been well studied and it is
established that these modifications play a key role in nuclear gene expression.
However, the status of mitochondrial epigenetic modifications has not been delved
in detail. The recent technological advancements in the genome analyzing tools
and techniques, have helped in investigating mitochondrial epigenetic
modifications with greater resolution and studies have indicated a regulatory
role of the mitochondrial epigenome. Association of mitochondrial DNA methylation
with various disease conditions, drug treatment, aging, exposure to environmental
pollutants etc. has lent credence to this belief. Herein, we have reviewed
studies on mitochondrial epigenetic modifications with a focus to comprehend its
regulatory role in gene expression and disease association.
PMID- 26437364
TI - Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA
interactions: Useful insights from aging and calorie restriction studies.
AB - Mitochondrial biogenesis is regulated to adapt mitochondrial population to cell
energy demands. Mitochondrial transcription factor A (TFAM) performs several
functions for mtDNA and interactions between TFAM and mtDNA participate to
regulation of mitochondrial biogenesis. Such interactions are modulated through
different mechanisms: regulation of TFAM expression and turnover, modulation of
TFAM binding activity to mtDNA through post-translational modifications and
differential affinity of TFAM, occurrence of TFAM sliding on mtDNA filaments and
of cooperative binding among TFAM molecules, modulation of protein-protein
interactions. The tissue-specific regulation of mitochondrial biogenesis in aging
and calorie restriction (CR) highlights the relevance of modulation of TFAM-mtDNA
interactions.
PMID- 26437367
TI - A lab-on-a-chip-based multiplex platform to detect potential fraud of introducing
pig, dog, cat, rat and monkey meat into the food chain.
AB - Food forgery has posed considerable risk to public health, religious rituals,
personal budget and wildlife. Pig, dog, cat, rat and monkey meat are restricted
in most religions, but their sporadic adulteration are rampant. Market
controllers need a low-cost but reliable technique to track and trace suspected
species in the food chain. Considering the need, here we documented a lab-on-a
chip-based multiplex polymerase chain reaction (PCR) assay for the authentication
of five non-halal meat species in foods. Using species-specific primers, 172,
163, 141, 129 and 108-bp sites of mitochondrial ND5, ATPase 6 and cytochrome b
genes were amplified to detect cat, dog, pig, monkey and rat species under
complex matrices. Species-specificity was authenticated against 20 different
species with the potential to be used in food. The targets were stable under
extreme sterilisation (121 degrees C at 45 psi for 2.5 h) which severely degrades
DNA. The assay was optimised under the backgrounds of various commercial meat
products and validated for the analysis of meatballs, burgers and frankfurters,
which are popular fast food items across the globe. The assay was tested to
detect 0.1% suspected meats under commercial backgrounds of marketed foods.
Instead of simplex PCR which detects only one species at a time, such a multiplex
platform can reduce cost by at least fivefolds by detecting five different
species in a single assay platform.
PMID- 26437368
TI - Meta-analysis of problem solving therapy for the treatment of major depressive
disorder in older adults.
AB - OBJECTIVE: Major depressive disorder (MDD) affects many older adults and is
associated with poor medical and mental health outcomes. Problem Solving Therapy
(PST) has emerged as a promising psychotherapy for MDD in older adults, although
the efficacy of PST in this population has not been well described. We examined
the effectiveness of PST for the treatment of MDD in older adults in a systematic
review and meta-analysis. METHODS: We searched electronic databases to identify
randomized controlled trials comparing PST to a control condition or other
treatment for MDD in adults with an average age of 60 years or older. We used
meta-analysis to arrive at pooled summary measures of the efficacy of PST when
compared to control conditions on the change in depressive symptoms and other
outcomes. RESULTS: Nine studies with a total of 569 participants (290 PST, 279
control) met inclusion criteria. Most studies administered PST in person and were
between 6 and 12 weeks in duration. Meta-analysis of six studies evaluating the
effect of PST on depression using the Hamilton Rating Scale for Depression
identified a significant reduction in depression associated with PST (pooled mean
difference = -6.94, 95%CI -10.91 to -2.97, d = 1.15, P = 0.0006). PST was also
effective in reducing disability in studies reporting this outcome. CONCLUSIONS:
Our review supports the existing research literature on PST suggesting that it is
an effective treatment for older people with MDD. Further study is required to
understand long-term outcomes associated with PST and its efficacy when compared
to other treatments.
PMID- 26437366
TI - Loss of BAP1 function leads to EZH2-dependent transformation.
AB - The tumor suppressors BAP1 and ASXL1 interact to form a polycomb deubiquitinase
complex that removes monoubiquitin from histone H2A lysine 119 (H2AK119Ub).
However, BAP1 and ASXL1 are mutated in distinct cancer types, consistent with
independent roles in regulating epigenetic state and malignant transformation.
Here we demonstrate that Bap1 loss in mice results in increased trimethylated
histone H3 lysine 27 (H3K27me3), elevated enhancer of zeste 2 polycomb repressive
complex 2 subunit (Ezh2) expression, and enhanced repression of polycomb
repressive complex 2 (PRC2) targets. These findings contrast with the reduction
in H3K27me3 levels seen with Asxl1 loss. Conditional deletion of Bap1 and Ezh2 in
vivo abrogates the myeloid progenitor expansion induced by Bap1 loss alone. Loss
of BAP1 results in a marked decrease in H4K20 monomethylation (H4K20me1).
Consistent with a role for H4K20me1 in the transcriptional regulation of EZH2,
expression of SETD8-the H4K20me1 methyltransferase-reduces EZH2 expression and
abrogates the proliferation of BAP1-mutant cells. Furthermore, mesothelioma cells
that lack BAP1 are sensitive to EZH2 pharmacologic inhibition, suggesting a novel
therapeutic approach for BAP1-mutant malignancies.
PMID- 26437365
TI - MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating
lipoprotein levels.
AB - The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for
clearing circulating LDL cholesterol (LDL-C). Whereas the transcriptional
regulation of LDLR is well characterized, the post-transcriptional mechanisms
that govern LDLR expression are just beginning to emerge. Here we develop a high
throughput genome-wide screening assay to systematically identify microRNAs
(miRNAs) that regulate LDLR activity in human hepatic cells. From this screen we
identified and characterized miR-148a as a negative regulator of LDLR expression
and activity and defined a sterol regulatory element-binding protein 1 (SREBP1)
mediated pathway through which miR-148a regulates LDL-C uptake. In mice,
inhibition of miR-148a increased hepatic LDLR expression and decreased plasma LDL
C. Moreover, we found that miR-148a regulates hepatic expression of ATP-binding
cassette, subfamily A, member 1 (ABCA1) and circulating high-density lipoprotein
cholesterol (HDL-C) levels in vivo. These studies uncover a role for miR-148a as
a key regulator of hepatic LDL-C clearance through direct modulation of LDLR
expression and demonstrate the therapeutic potential of inhibiting miR-148a to
ameliorate an elevated LDL-C/HDL-C ratio, a prominent risk factor for
cardiovascular disease.
PMID- 26437369
TI - JC polyomavirus viremia and progressive multifocal leukoencephalopathy in human
leukocyte antigen-sensitized kidney transplant recipients desensitized with
intravenous immunoglobulin and rituximab.
AB - BACKGROUND: Desensitization (DES) with intravenous immunoglobulin (IVIG) +
rituximab is effective, safe, and increases the transplantation rate in human
leukocyte antigen-sensitized patients. However, reports of progressive multifocal
leukoencephalopathy (PML) caused by JC polyomavirus (JCPyV) in autoimmune
patients treated with rituximab is concerning. Here, we report on the JCPyV
viremia and PML status in kidney transplant patients with/without DES (non-DES).
METHODS: In total 1195 and 699 DNA samples from plasma in 117 DES (78% lymphocyte
depleting [LyD] induction) and 100 non-DES patients (45% LyD), respectively, were
submitted for JCPyV-polymerase chain reaction. Results were compared in both
groups. RESULTS: No patients in either DES or non-DES developed PML or presented
with any neurological symptoms. The JCPyV viremia rate was similar in DES and non
DES patients (3/117 vs. 9/100, P = 0.07). The JCPyV levels were low (median peak
levels, 1025 copies/mL) and JCPyV viremia was observed only once during the study
period in most patients. All 3 DES patients with JCPyV(+) received 1 dose
rituximab and no DES patients with >1 dose rituximab showed JCPyV(+). All 3
JCPyV(+) DES patients received LyD induction, while only 2 of 9 JCPyV(+) non-DES
patients did so, and the remaining 7 received non-LyD or no induction. JCPyV in
leukocyte was mostly negative in DES and non-DES patients. Immunosuppression in
patients with or without JCPyV(+) was similar. BK polyomavirus viremia was
observed more commonly in patients with JCPyV(+) than in those without (P <
0.02). CONCLUSIONS: Patients with IVIG + rituximab DES followed by
transplantation with LyD induction and additional rituximab rarely show JCPyV
viremia and appear at low risk for PML.
PMID- 26437370
TI - CT-Based Morphological Analysis of Isolated Inferior and Medial Blow-out Orbital
Fractures in Korean Adults.
AB - PURPOSE: To evaluate morphologic differences in isolated inferior medial orbital
wall fractures (OWF) based on computed tomography scans. METHODS: This was a
retrospective observational case study of 22 patients with an isolated inferior
OWF and 32 patients with an isolated medial fracture between January 2008 and
August 2010. We analyzed patient demographics and bony radiologic characteristics
on CT scans, including the length and height of the lamina papyracea, the number
of ethmoid air cell septa, the length of the anterior and posterior border of the
orbital floor, the thickness of the orbital floor maxillary bone, and the axial
length of the eyeball. RESULTS: There were no significant differences in sex,
laterality, or concomitant intraocular injury between the two groups. The
anteroposterior length (p = 0.391), the number of ethmoid septa (p = 0.869), and
the thickness of the orbital floor (p = 0.419) did not differ significantly. The
anterior (p < 0.001) or posterior (p = 0.014) height of the lamina papyracea, the
lamina papyracea area (p < 0.001), and the lamina papyracea area/ethmoid air cell
septa (p = 0.024) were significantly higher in the medial OWF group, while the
anterior (p = 0.026) or posterior (p < 0.001) border length of the orbital floor
and the axial length (p = 0.047) and volume (p = 0.034) of the eyeball were
longer and smaller, respectively, in the inferior OWF group. CONCLUSIONS:
Patients with a longer anterior or posterior border of the orbital floor, a
shorter axial length, and a smaller eyeball volume are more likely to incur an
isolated inferior OWF than an isolated medial OWF.
PMID- 26437371
TI - Nonpolar m-plane GaN/AlGaN heterostructures with intersubband transitions in the
5-10 THz band.
AB - This paper assesses intersubband (ISB) transitions in the 1-10 THz frequency
range in nonpolar m-plane GaN/AlGaN multi-quantum-wells deposited on free
standing semi-insulating GaN substrates. The quantum wells (QWs) were designed to
contain two confined electronic levels, decoupled from the neighboring wells.
Structural analysis reveals flat and regular QWs in the two perpendicular in
plane directions, with high-angle annular dark-field scanning transmission
electron microscopy images showing inhomogeneities of the Al composition in the
barriers along the growth axis. We do not observe extended structural defects
(stacking faults or dislocations) introduced by the epitaxial process. Low
temperature ISB absorption from 1.5 to 9 THz (6.3-37.4 meV) is demonstrated,
covering most of the 7-10 THz band forbidden to GaAs-based technologies.
PMID- 26437373
TI - The effect of antiepileptic drugs on thyroid hormonal function: causes and
implications.
AB - Epilepsy is a chronic disease and its treatment is lifelong in one-third of
patients. Data from cross-sectional and prospective studies have reviewed the
influence of antiepileptic drugs (AEDs) on thyroid hormones. Thyroid
abnormalities were reported in one-third of the patients on AEDs. Subclinical
hypothyroidism, reduced thyroxine, triiodothyronine, free thyroxine, free
triiodothyronine and thyroid binding globulin concentrations were reported with
phenobarbital, phenytoin, carbamazepine, valproate and oxcarbazepine, but not
with lamotrigine, levitracetam, tiagabine and vigabatrine. All reported patients
were clinically euthyroid and hormonal changes were reversible after AED
withdrawal. The mechanisms for thyroid dysfunction with AEDs include enhanced
metabolism and/or altered protein binding or interference of hypothalamic
pituitary-thyroid axis function. This review focuses on the evidence, mechanisms
of thyroid abnormalities with AEDs and their clinical implications. The
associations between subclinical hypothyroidism and metabolic risks due to AEDs
are also discussed.
PMID- 26437372
TI - Reconciling Estimates of Cell Proliferation from Stable Isotope Labeling
Experiments.
AB - Stable isotope labeling is the state of the art technique for in vivo
quantification of lymphocyte kinetics in humans. It has been central to a number
of seminal studies, particularly in the context of HIV-1 and leukemia. However,
there is a significant discrepancy between lymphocyte proliferation rates
estimated in different studies. Notably, deuterated (2)H2-glucose (D2-glucose)
labeling studies consistently yield higher estimates of proliferation than
deuterated water (D2O) labeling studies. This hampers our understanding of immune
function and undermines our confidence in this important technique. Whether these
differences are caused by fundamental biochemical differences between the two
compounds and/or by methodological differences in the studies is unknown. D2
glucose and D2O labeling experiments have never been performed by the same group
under the same experimental conditions; consequently a direct comparison of these
two techniques has not been possible. We sought to address this problem. We
performed both in vitro and murine in vivo labeling experiments using identical
protocols with both D2-glucose and D2O. This showed that intrinsic differences
between the two compounds do not cause differences in the proliferation rate
estimates, but that estimates made using D2-glucose in vivo were susceptible to
difficulties in normalization due to highly variable blood glucose enrichment.
Analysis of three published human studies made using D2-glucose and D2O confirmed
this problem, particularly in the case of short term D2-glucose labeling.
Correcting for these inaccuracies in normalization decreased proliferation rate
estimates made using D2-glucose and slightly increased estimates made using D2O;
thus bringing the estimates from the two methods significantly closer and
highlighting the importance of reliable normalization when using this technique.
PMID- 26437374
TI - Anxiety and retrieval inhibition: support for an enhanced inhibition account.
AB - Retrieval inhibition of negative associations is important for exposure therapy
for anxiety, but the relationship between memory inhibition and anxiety is not
well understood-anxiety could either be associated with enhanced or deficient
inhibition. The present study tested these two competing hypotheses by measuring
retrieval inhibition of negative stimuli by related neutral stimuli. Non
clinically anxious undergraduates completed measures of trait and state anxiety
and completed a retrieval induced forgetting task. Adaptive forgetting varied
with state anxiety. Low levels of state anxiety were associated with no evidence
for retrieval inhibition for either threatening or non-threatening categories.
Participants in the middle tertile of state anxiety scores exhibited retrieval
inhibition for non-threatening categories but not for threatening categories.
Participants in the highest tertile of state anxiety, however, exhibited
retrieval inhibition for both threatening and non-threatening categories with the
magnitude of retrieval inhibition being greater for threatening than non
threatening categories. The data are in line with the avoidance aspect of the
vigilance-avoidance theory of anxiety and inhibition. Implications for cognitive
behavioural therapy practices are discussed.
PMID- 26437375
TI - Cytokines in Neuropathic Pain and Associated Depression.
AB - Neuropathic pain occurs as a result of lesion or disease affecting the
somatosensory nervous system and is present in a diverse set of peripheral and
central pathologies such as nerve trauma, diabetic neuropathy, post-herpetic
neuralgia, chemotherapy-induced peripheral neuropathy, spinal cord injury and
multiple sclerosis. Debilitating symptoms including allodynia, hyperalgesia and
spontaneous pain have a substantial negative impact on patients' quality of life.
The currently available therapeutic treatments are generally ineffective and
characterised by poor response rates. Accumulating evidence suggests that
neuroinflammation and cytokine signalling play a critical role in neuropathic
pain. Numerous experimental studies have demonstrated that certain pro
inflammatory cytokines are elevated in neuropathic pain conditions, and
administration of these cytokines can elicit pain hypersensitivity in the absence
of injury or disease. This phenomenon is also apparent in the 'sickness
response', which encompasses a broad inflammatory response to disease and injury
and involves a series of physiological and behavioural changes including pain
hypersensitivity. Interestingly, the 'sickness response' is also similar in
nature to some of the defining characteristics of the depressed state of
affective disorder. In this review, we explore links that may relate the co
existence of depression in neuropathic pain patients with the activity of
cytokines and discuss the role of several key pro-inflammatory and anti
inflammatory cytokines in neuropathic pain.
PMID- 26437376
TI - Effect of scavenger receptor class B type I antagonist ITX5061 in patients with
hepatitis C virus infection undergoing liver transplantation.
AB - Hepatitis C virus (HCV) entry inhibitors have been hypothesized to prevent
infection of the liver after transplantation. ITX5061 is a scavenger receptor
class B type I antagonist that blocks HCV entry and infection in vitro. We
assessed the safety and efficacy of ITX5061 to limit HCV infection of the graft.
The study included 23 HCV-infected patients undergoing liver transplantation. The
first 13 "control" patients did not receive drug. The subsequent 10 patients
received 150 mg of ITX5061 immediately before and after transplant and daily for
1 week thereafter. ITX5061 pharmacokinetics and plasma HCV RNA were quantified.
Viral genetic diversity was measured by ultradeep pyrosequencing (UDPS). ITX5061
was well tolerated with measurable plasma concentrations during therapy. Although
the median HCV RNA reduction was greater in ITX-treated patients at all time
points in the first week after transplantation, there was no difference in the
overall change in the area over the HCV RNA curve in the 7-day treatment period.
However, in genotype (GT) 1-infected patients, treatment was associated with a
sustained reduction in HCV RNA levels compared to the control group (area over
the HCV RNA curve analysis, P = 0.004). UDPS revealed a complex and evolving
pattern of HCV variants infecting the graft during the first week. ITX5061
significantly limited viral evolution where the median divergence between day 0
and day 7 was 3.5% in the control group compared to 0.1% in the treated group. In
conclusion, ITX5061 reduces plasma HCV RNA after transplant notably in GT 1
infected patients and slows viral evolution. Following liver transplantation, the
likely contribution of extrahepatic reservoirs of HCV necessitates combining
entry inhibitors such as ITX5061 with inhibitors of replication in future
studies.
PMID- 26437378
TI - Enzyme-Powered Hollow Mesoporous Janus Nanomotors.
AB - The development of synthetic nanomotors for technological applications in
particular for life science and nanomedicine is a key focus of current basic
research. However, it has been challenging to make active nanosystems based on
biocompatible materials consuming nontoxic fuels for providing self-propulsion.
Here, we fabricate self-propelled Janus nanomotors based on hollow mesoporous
silica nanoparticles (HMSNPs), which are powered by biocatalytic reactions of
three different enzymes: catalase, urease, and glucose oxidase (GOx). The active
motion is characterized by a mean-square displacement (MSD) analysis of optical
video recordings and confirmed by dynamic light scattering (DLS) measurements. We
found that the apparent diffusion coefficient was enhanced by up to 83%. In
addition, using optical tweezers, we directly measured a holding force of 64 +/-
16 fN, which was necessary to counteract the effective self-propulsion force
generated by a single nanomotor. The successful demonstration of biocompatible
enzyme-powered active nanomotors using biologically benign fuels has a great
potential for future biomedical applications.
PMID- 26437377
TI - Effect of Roux-en-Y Gastric Bypass on the NLRP3 Inflammasome in Adipose Tissue
from Obese Rats.
AB - OBJECTIVE: Obesity is associated with low-grade chronic inflammation. We
hypothesized that Roux-en-Y gastric bypass (RYGB) surgery would reduce activation
of the NLRP3 inflammasome in metabolically active adipose tissue (AT) of obese
rats, and this change would be related to decreases in body weight and improved
glycemic control. METHODS: Omental, mesenteric and subcutaneous fat depots were
collected from Sprague-Dawley rats: Sham control and RYGB; 90-days after surgery.
NLRP3, caspase-1, apoptosis-associated speck-like protein (ASC), IL-1beta, IL-18,
IL-6 and MCP-1 gene and protein expression were quantified. Glucose metabolism
was assessed by oral glucose tolerance test (OGTT). RESULTS: Compared to Sham
surgery controls, RYGB surgery decreased IL-6, MCP-1, NLRP3, IL-18, caspase-1 and
ASC in omental fat, and decreased IL-6, MCP1, IL-1beta, IL-18, caspase-1 and ASC
gene expression in mesenteric fat. We observed differential gene expression
between visceral and subcutaneous fat for IL-6 and IL-1beta, both being
downregulated by RYGB in visceral, and upregulated in subcutaneous depots. These
changes in gene expression were accompanied by a decrease in NLRP3, ASC, IL-18,
caspase-1 and IL-1beta protein expression in omental tissue. We found a positive
correlation between caspase-1, ASC, MCP-1, IL-18 and IL-6 gene expression
following surgery and glucose AUC response in omental fat, while the change in
glucose AUC response correlated with caspase-1 gene expression in subcutaneous
fat. CONCLUSION: This study demonstrates that bariatric surgery reverses
inflammation in visceral adipose tissue by suppressing NLRP3 inflammasome
activation. These are the first data to implicate the NLRP3 inflammasome in
diabetes remission after RYGB surgery.
PMID- 26437379
TI - Neuroprotective effects of crocin against oxidative stress induced by
ischemia/reperfusion injury in rat retina.
AB - AIMS: Crocin, a pharmacologically active component of Crocus sativus L.
(saffron), has been reported to be useful in the treatment of oxidative stress
injury. In the present study, we investigated the antioxidative effect of crocin
and the change of the ERK signaling pathway on rat retina induced by
ischemia/reperfusion (IR) injury. METHODS: Crocin was pretreated 30 min before
and once daily after retinal IR injury by intraperitoneal injection. The retinal
morphological damage was observed by hematoxylin and eosin (HE) staining. The
number of retinal ganglion cells (RGCs) was counted by Brn-3a immunofluorescence
staining. The antiapoptotic effect of crocin was determined by detecting cleaved
caspase-3 protein levels by means of Western blot and immunohistochemical
analysis. Furthermore, retinas were also used for the determination of
malondialdehyde (MDA) levels, glutathione (GSH) levels, total superoxide
dismutase (T-SOD), and reactive oxygen species (ROS). The phosphorylated ERK (p
ERK) protein level was determined by Western blot and immunohistochemical
analysis. RESULTS: Our results showed that crocin treatment (50 mg/kg)
significantly inhibited the decrease of retinal thickness through HE staining and
protected RGCs from decreasing. Compared with the IR + vehicle group, crocin
treatment significantly decreased cleaved caspase-3 and p-ERK protein expression
by Western blot analysis and immunohistochemistry. Immunohistochemical staining
for cleaved caspase-3 and p-ERK in the retinal sections showed positive cells
were present in the RGC layer and inner nuclear layer after IR injury. Similarly,
crocin (50 mg/kg) treatment also significantly increased the level of activity of
GSH, enhanced the activity of T-SOD, and decreased the activity level of ROS and
MDA after IR injury. CONCLUSIONS: These findings demonstrated that crocin
treatment could notably protect the retina from damage induced by IR. It might be
related to crocin antioxidant and antiapoptotic properties in the retina.
PMID- 26437381
TI - Mesenchymal stem cells as novel micro-ribonucleic acid delivery vehicles in
kidney disease.
AB - MicroRNAs (miRNAs) are short single strands of RNA responsible for post
transcriptional regulation of gene expression and have been implicated in the
pathogenesis of chronic kidney disease (CKD). Emerging evidence reports that
miRNAs can reduce kidney fibrosis through regulation of targets associated with
collagen and extracellular matrix accumulation. However, the development of miRNA
therapies has been hampered by the lack of targeted and sustainable methods of
systemic miRNA delivery. Mesenchymal stem cells (MSCs) provide a promising miRNA
delivery platform to overcome toxicity, the potential for insertional mutations
and the low efficiency of previous methods. MSCs are endogenously
immunoprivileged and home to sites of inflammation. They also release trophic
growth factors to modulate the immune system, alter the polarization of
macrophages and provide renal protection and repair. The potential to engineer
MSCs to express or overexpress miRNAs, released by exosomes, may enhance their
natural functions. Clinical studies are already being conducted individually for
the use of miRNAs in cancer and MSCs in diseases associated with CKD. Hence, the
combination of miRNAs and MSCs may provide an unparalleled cell-based therapy for
treating CKD.
PMID- 26437380
TI - Anti-Apoptotic Effects of 3,3',5-Triiodo-L-Thyronine in the Liver of Brain-Dead
Rats.
AB - BACKGROUND: Thyroid hormone treatment in brain-dead organ donors has been
extensively studied and applied in the clinical setting. However, its clinical
applicability remains controversial due to a varying degree of success and a lack
of mechanistic understanding about the therapeutic effects of 3,3',5-Triiodo-L
thyronine (T3). T3 pre-conditioning leads to anti-apoptotic and pro-mitotic
effects in liver tissue following ischemia/reperfusion injury. Therefore, we
aimed to study the effects of T3 pre-conditioning in the liver of brain-dead
rats. METHODS: Brain death (BD) was induced in mechanically ventilated rats by
inflation of a Fogarty catheter in the epidural space. T3 (0.1 mg/kg) or vehicle
was administered intraperitoneally 2 h prior to BD induction. After 4 h of BD,
serum and liver tissue were collected. RT-qPCR, routine biochemistry, and
immunohistochemistry were performed. RESULTS: Brain-dead animals treated with T3
had lower plasma levels of AST and ALT, reduced Bax gene expression, and less
hepatic cleaved Caspase-3 activation compared to brain-dead animals treated with
vehicle. Interestingly, no differences in the expression of inflammatory genes
(IL-6, MCP-1, IL-1beta) or the presence of pro-mitotic markers (Cyclin-D and Ki
67) were found in brain-dead animals treated with T3 compared to vehicle-treated
animals. CONCLUSION: T3 pre-conditioning leads to beneficial effects in the liver
of brain-dead rats as seen by lower cellular injury and reduced apoptosis, and
supports the suggested role of T3 hormone therapy in the management of brain-dead
donors.
PMID- 26437382
TI - Modification of a Colliculo-thalamocortical Mouse Brain Slice, Incorporating 3-D
printing of Chamber Components and Multi-scale Optical Imaging.
AB - The ability of the brain to process sensory information relies on both ascending
and descending sets of projections. Until recently, the only way to study these
two systems and how they interact has been with the use of in vivo preparations.
Major advances have been made with acute brain slices containing the
thalamocortical and cortico-thalamic pathways in the somatosensory, visual, and
auditory systems. With key refinements to our recent modification of the auditory
thalamocortical slice(1), we are able to more reliably capture the projections
between most of the major auditory midbrain and forebrain structures: the
inferior colliculus (IC), medial geniculate body (MGB), thalamic reticular
nucleus (TRN), and the auditory cortex (AC). With portions of all these
connections retained, we are able to answer detailed questions that complement
the questions that can be answered with in vivo preparations. The use of
flavoprotein autofluorescence imaging enables us to rapidly assess connectivity
in any given slice and guide the ensuing experiment. Using this slice in
conjunction with recording and imaging techniques, we are now better equipped to
understand how information processing occurs at each point in the auditory
forebrain as information ascends to the cortex, and the impact of descending
cortical modulation. 3-D printing to build slice chamber components permits
double-sided perfusion and broad access to networks within the slice and
maintains the widespread connections key to fully utilizing this preparation.
PMID- 26437383
TI - Extinction and spontaneous recovery of spatial behavior in pigeons.
AB - We investigated extinction and spontaneous recovery of spatial associations using
a landmark-based appetitive search task in a touchscreen preparation with
pigeons. Four visual landmarks (A, B, C, and D) were separately established as
signals of a hidden reinforced target among an 8 * 7 array of potential target
locations. The target was located above landmarks (LM) A and C and below B and D.
After conditioning, A and B were extinguished. Responding to A and C was assessed
on probe tests 2 days following extinction, whereas, B and D were tested 14 days
after extinction. We observed spontaneous recovery from spatial extinction
following a 14-day, but not a 2-day, postextinction retention interval.
Furthermore, by plotting the spatial distribution of responding across the X and
Y axes during testing, we found that spontaneous recovery of responding to the
target in our task was due to enhanced spatial control (i.e., a change in the
overall distribution of responses) following the long delay to testing. These
results add spatial extinction and spontaneous recovery to the list of findings
supporting the assertion that extinction involves new learning that attenuates
the originally acquired response, and that original learning of the spatial
relationship between paired events survives extinction. (PsycINFO Database Record
PMID- 26437384
TI - Responses compete and collaborate, shaping each others' distributions: Commentary
on Boakes, Patterson, Kendig, and Harris (2015).
AB - Boakes, Patterson, Kendig, and Harris (2015) showed that schedule-induced
drinking (SID), typically concentrated in the first half of the interpellet
interval, is not moved there exclusively by competition from magazine entries,
and that not all arbitrary responses can be maintained by adventitious
reinforcement. They attribute such inferences to Killeen and Pellon (2013) and
Patterson and Boakes (2012), and on that basis reject their explanation for the
excessive nature of many adjunctive responses as a result of reinforcement. It is
a mistaken attribution, as Killeen and Pellon emphasized that reinforcers act on
many competing interim and terminal responses. That attribution is a minor
oversight on the authors' part; their return to a discredited motivational
account is, however, a major blunder. It discards the seminal recent advances in
understanding the nature of schedule-induced responses (e.g., those of Patterson
and Boakes), and even the positive contributions of their own article: Their data
show very strong correlations between magazine entries and drinking, providing
much more evidence for response competition than their microanalysis provides
against it.
PMID- 26437385
TI - Reply to Pellon and Killeen's (2015) commentary on Boakes, Patterson, Kendig, and
Harris (2015).
AB - This reply notes the importance of data from variable-time schedules for
resolving the issue of whether competition from magazine approach behavior is a
major factor responsible for the concentration of schedule-induced drinking early
in interpellet intervals. Pellon and Killeen propose that this temporal
distribution of schedule-induced drinking reflects the effectiveness of
adventitious reinforcement of this behavior over a delay, as detailed in their
model. However, there is no evidence to support either of their key assumptions:
(a) that schedule-induced behaviors are maintained by adventitious reinforcement
("are operants") and (b) that behaviors vary in their sensitivity to a delay
before the subsequent occurrence of a reinforcer.
PMID- 26437386
TI - Disparities in Time Spent Seeking Medical Care in the United States.
PMID- 26437387
TI - Amyotrophic lateral sclerosis progression: Iran-ALS clinical registry, a
multicentre study.
AB - This study was designed to evaluate ALS progression among different subgroups of
Iranian patients. Three hundred and fifty-eight patients from centres around the
country were registered and their progression rate was evaluated using several
scores including Manual Muscle Test scoring (MMT) and the revised ALS Functional
Rating Scale (ALSFRS-R). Progression rate was analysed separately in subgroups
regarding gender, onset site, stage of disease and riluzole consumption. A
significant difference in MMT deterioration rate (p = 0.01) was noted between
those who used riluzole and those who did not. No significant difference was
observed in progression rates between male/female and bulbar-onset/limb-onset
groups using riluzole. In conclusion, riluzole has a significant effect on muscle
force deterioration rate but not functional scale. Progression rate was not
influenced by site of onset or gender.
PMID- 26437389
TI - Ionic Liquid-Based Ultrasonic-Assisted Extraction of Secoisolariciresinol
Diglucoside from Flaxseed (Linum usitatissimum L.) with Further Purification by
an Aqueous Two-Phase System.
AB - In this work, a two-step extraction methodology of ionic liquid-based ultrasonic
assisted extraction (IL-UAE) and ionic liquid-based aqueous two-phase system (IL
ATPS) was developed for the extraction and purification of secoisolariciresinol
diglucoside (SDG) from flaxseed. In the IL-UAE step, several kinds of ILs were
investigated as the extractants, to identify the IL that affords the optimum
extraction yield. The extraction conditions such as IL concentration, ultrasonic
irradiation time, and liquid-solid ratio were optimized using response surface
methodology (RSM). In the IL-ATPS step, ATPS formed by adding kosmotropic salts
to the IL extract was used for further separation and purification of SDG. The
most influential parameters (type and concentration of salt, temperature, and pH)
were investigated to obtain the optimum extraction efficiency. The maximum
extraction efficiency was 93.35% under the optimal conditions of 45.86% (w/w) IL
and 8.27% (w/w) Na2SO4 at 22 degrees C and pH 11.0. Thus, the combination of IL
UAE and IL-ATPS makes up a simple and effective methodology for the extraction
and purification of SDG. This process is also expected to be highly useful for
the extraction and purification of bioactive compounds from other important
medicinal plants.
PMID- 26437390
TI - Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis.
AB - The liver has become an increasingly interesting target for oligonucleotide
therapy. Mutations of the gene encoding transthyretin (TTR), expressed in vast
amounts by the liver, result in a complex degenerative disease, termed familial
amyloid polyneuropathy (FAP). Misfolded variants of TTR are linked to the
establishment of extracellular protein deposition in various tissues, including
the heart and the peripheral nervous system. Recent progress in the chemistry and
formulation of antisense (ASO) and small interfering RNA (siRNA) designed for a
knockdown of TTR mRNA in the liver has allowed to address the issue of gene
specific molecular therapy in a clinical setting of FAP. The two therapeutic
oligonucleotides bind to RNA in a sequence specific manner but exploit different
mechanisms. Here we describe major developments that have led to the advent of
therapeutic oligonucleotides for treatment of TTR-related disease.
PMID- 26437391
TI - Comparative Studies on Phenolic Composition, Antioxidant, Wound Healing and
Cytotoxic Activities of Selected Achillea L. Species Growing in Turkey.
AB - Turkey is one of the most important centers of diversity for the genus Achillea
L. in the world. Keeping in mind the immense medicinal importance of phenols, in
this study, three species growing in Turkey, A. coarctata Poir. (AC), A. kotschyi
Boiss. subsp. kotschyi (AK) and A. lycaonica Boiss. & Heldr. (AL) were evaluated
for their phenolic compositions, total phenolic contents (TPC), antioxidant
properties, wound healing potencies on NIH-3T3 fibroblasts and cytotoxic effects
on MCF-7 human breast cancer cells. Comprehensive LC-MS/MS analysis revealed that
AK was distinctively rich in chlorogenic acid, hyperoside, apigenin, hesperidin,
rutin, kaempferol and luteolin (2890.6, 987.3, 797.0, 422.5, 188.1, 159.4 and
121.2 ug analyte/g extract, respectively). The findings exhibited a strong
correlation between TPC and both free radical scavenging activity and total
antioxidant capacity (TAC). Among studied species, the highest TPC (148.00 mg
GAE/g extract) and TAC (2.080 UAE), the strongest radical scavenging (EC50 =
32.63 MUg/mL), the most prominent wound healing and most abundant cytotoxic
activities were observed with AK. The results suggested that AK is a valuable
source of flavonoids and chlorogenic acid with important antioxidant, wound
healing and cytotoxic activities. These findings warrant further studies to
assess the potential of AK as a bioactive source that could be exploited in
pharmaceutical, cosmetics and food industries.
PMID- 26437392
TI - Cucurbitacins from the Leaves of Citrullus colocynthis (L.) Schrad.
AB - Two new tetracyclic cucurbitane-type triterpene glycosides were isolated from an
ethyl acetate extract of Citrullus colocynthis leaves together with four known
cucurbitacins. Their structures were established on the basis of their
spectroscopic data (mainly NMR and mass spectrometry). Evaluation of the in vitro
cytotoxic activity of the isolated compounds against two human colon cancer cell
lines (HT29 and Caco-2) and one normal rat intestine epithelial cell line (IEC6),
revealed that one of the isolated compounds presented interesting specific
cytotoxic activity towards colorectal cell lines.
PMID- 26437393
TI - Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic
Drug Targeting in Multicellular Tumor Spheroids.
AB - Major problems of cancer treatment using systemic chemotherapy are severe side
effects. Magnetic drug targeting (MDT) employing superparamagnetic iron oxide
nanoparticles (SPION) loaded with chemotherapeutic agents may overcome this
dilemma by increasing drug accumulation in the tumor and reducing toxic side
effects in the healthy tissue. For translation of nanomedicine from bench to
bedside, nanoparticle-mediated effects have to be studied carefully. In this
study, we compare the effect of SPION, unloaded or loaded with the cytotoxic drug
mitoxantrone (MTO) with the effect of free MTO, on the viability and
proliferation of HT-29 cells within three-dimensional multicellular tumor
spheroids. Fluorescence microscopy and flow cytometry showed that both free MTO,
as well as SPION-loaded MTO (SPION(MTO)) are able to penetrate into tumor
spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect
cellular viability. Since SPION(MTO) has herewith proven its effectivity also in
complex multicellular tumor structures with its surrounding microenvironment, we
conclude that it is a promising candidate for further use in magnetic drug
targeting in vivo.
PMID- 26437394
TI - Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine,
Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in
Rats.
AB - Most orally administered polyphenols are metabolized, with very little absorbed
as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are
therefore necessary to understand the pharmacological mechanisms of polyphenols.
Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment
of skin diseases including inflammatory acne. Because JHT contains various types
of bioactive polyphenols, our aim was to clarify the metabolism and
pharmacokinetics of the polyphenols in JHT and identify active metabolites
contributing to its antidermatitis effects. Orally administered JHT inhibited the
increase in ear thickness in rats induced by intradermal injection of
Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains
various types of flavonoids and is also rich in hydrolysable tannins, such as
1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses
showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and
liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to
inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic
acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the
nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis
probably via the antioxidant effect of its metabolites. Our study is beneficial
for understanding in vivo actions of orally administered polyphenol drugs.
PMID- 26437395
TI - Metabolic Profiling of Alpine and Ecuadorian Lichens.
AB - Non-targeted 1H-NMR methods were used to determine metabolite profiles from crude
extracts of Alpine and Ecuadorian lichens collected from their natural habitats.
In control experiments, the robustness of metabolite detection and quantification
was estimated using replicate measurements of Stereocaulon alpinum extracts. The
deviations in the overall metabolite fingerprints were low when analyzing S.
alpinum collections from different locations or during different annual and
seasonal periods. In contrast, metabolite profiles observed from extracts of
different Alpine and Ecuadorian lichens clearly revealed genus- and species
specific profiles. The discriminating functions determining cluster formation in
principle component analysis (PCA) were due to differences in the amounts of
genus-specific compounds such as sticticin from the Sticta species, but also in
the amounts of ubiquitous metabolites, such as sugar alcohols or trehalose.
However, varying concentrations of these metabolites from the same lichen species
e.g., due to different environmental conditions appeared of minor relevance for
the overall cluster formation in PCA. The metabolic clusters matched phylogenetic
analyses using nuclear ribosomal DNA (nrDNA) internal transcribed spacer (ITS)
sequences of lichen mycobionts, as exemplified for the genus Sticta. It can be
concluded that NMR-based non-targeted metabolic profiling is a useful tool in the
chemo-taxonomy of lichens. The same approach could also facilitate the discovery
of novel lichen metabolites on a rapid and systematical basis.
PMID- 26437396
TI - Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA
Splicing Regulatory Genes.
AB - Abnormalities in RNA metabolism and alternative splicing (AS) are emerging as
important players in complex disease phenotypes. In particular, accumulating
evidence suggests the existence of pathogenic links between multiple sclerosis
(MS) and altered AS, including functional studies showing that an imbalance in
alternatively-spliced isoforms may contribute to disease etiology. Here, we
tested whether the altered expression of AS-related genes represents a MS
specific signature. A comprehensive comparative analysis of gene expression
profiles of publicly-available microarray datasets (190 MS cases, 182 controls),
followed by gene-ontology enrichment analysis, highlighted a significant
enrichment for differentially-expressed genes involved in RNA metabolism/AS. In
detail, a total of 17 genes were found to be differentially expressed in MS in
multiple datasets, with CELF1 being dysregulated in five out of seven studies. We
confirmed CELF1 downregulation in MS (p=0.0015) by real-time RT-PCRs on RNA
extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we
experimentally verified the unbalance in alternatively-spliced isoforms in MS of
the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we
provide evidence of a consistent dysregulation of splicing-related genes in MS
and we discuss its possible implications in modulating specific AS events in MS
susceptibility genes.
PMID- 26437397
TI - Mutagenic Effects of Iron Oxide Nanoparticles on Biological Cells.
AB - In recent years, there has been an increased interest in the design and use of
iron oxide materials with nanoscale dimensions for magnetic, catalytic,
biomedical, and electronic applications. The increased manufacture and use of
iron oxide nanoparticles (IONPs) in consumer products as well as industrial
processes is expected to lead to the unintentional release of IONPs into the
environment. The impact of IONPs on the environment and on biological species is
not well understood but remains a concern due to the increased chemical
reactivity of nanoparticles relative to their bulk counterparts. This review
article describes the impact of IONPs on cellular genetic components. The
mutagenic impact of IONPs may damage an organism's ability to develop or
reproduce. To date, there has been experimental evidence of IONPs having
mutagenic interactions on human cell lines including lymphoblastoids,
fibroblasts, microvascular endothelial cells, bone marrow cells, lung epithelial
cells, alveolar type II like epithelial cells, bronchial fibroblasts, skin
epithelial cells, hepatocytes, cerebral endothelial cells, fibrosarcoma cells,
breast carcinoma cells, lung carcinoma cells, and cervix carcinoma cells. Other
cell lines including the Chinese hamster ovary cells, mouse fibroblast cells,
murine fibroblast cells, Mytilus galloprovincialis sperm cells, mice lung cells,
murine alveolar macrophages, mice hepatic and renal tissue cells, and vero cells
have also shown mutagenic effects upon exposure to IONPs. We further show the
influence of IONPs on microorganisms in the presence and absence of dissolved
organic carbon. The results shed light on the OPEN ACCESS Int. J. Mol. Sci. 2015,
16 23483 transformations IONPs undergo in the environment and the nature of the
potential mutagenic impact on biological cells.
PMID- 26437398
TI - Systematic Analysis of the Maize PHD-Finger Gene Family Reveals a Subfamily
Involved in Abiotic Stress Response.
AB - Plant homeodomain (PHD)-finger proteins were found universally in eukaryotes and
known as key players in regulating transcription and chromatin structure. Many
PHD-finger proteins have been well studied on structure and function in animals.
Whereas, only a few of plant PHD-finger factors had been characterized, and
majority of PHD-finger proteins were functionally unclear. In this study, a
complete comprehensive analysis of maize PHD family is presented. Sixty-seven PHD
finger genes in maize were identified and further divided into ten groups
according to phylogenetic analysis that was supported by motif and intron/exon
analysis. These genes were unevenly distributed on ten chromosomes and contained
12 segmental duplication events, suggesting that segmental duplications were the
major contributors in expansion of the maize PHD family. The paralogous genes
mainly experienced purifying selection with restrictive functional divergence
after the duplication events on the basis of the Ka/Ks ratio. Gene digital
expression analysis showed that the PHD family had a wide expression profile in
maize development. In addition, 15 potential stress response genes were detected
by promoter cis-element and expression analysis. Two proteins ZmPHD14 and ZmPHD19
were located in the nucleus. These results provided a solid base for future
functional genome study of the PHD-finger family in maize and afforded important
clues for characterizing and cloning potentially important candidates in response
to abiotic stresses.
PMID- 26437399
TI - A Large-Scale Analysis of the Relationship of Synonymous SNPs Changing MicroRNA
Regulation with Functionality and Disease.
AB - Historically, owing to not changing amino acid composition of protein sequences,
synonymous mutations are commonly assumed to be neutral during evolution and
therefore have no effect on the phenotype and disease. Here, based on
observations from large-scale analysis of genomic data, we predicted the putative
synonymous SNPs that could result in functional consequences and disease risk
through changing the microRNA-mediated gene regulation. We found that nearly half
of the synonymous SNPs could affect protein expression by changing microRNA
regulation in human genome and these SNPs significantly prefer to be associated
with human diseases and traits. The synonymous SNPs changing microRNA-mediated
gene regulation tend to be more under recent positive selection, prefer to affect
gene expression, and implicate in human disease. We conclude that the miRNA
mediated regulation changes could be a potential mechanism for the contributions
of synonymous SNPs to protein functions and disease risks.
PMID- 26437400
TI - Systemically Administered, Target Organ-Specific Therapies for Regenerative
Medicine.
AB - Growth factors and other agents that could potentially enhance tissue
regeneration have been identified, but their therapeutic value in clinical
medicine has been limited for reasons such as difficulty to maintain bioactivity
of locally applied therapeutics in the protease-rich environment of regenerating
tissues. Although human diseases are treated with systemically administered drugs
in general, all current efforts aimed at enhancing tissue repair with biological
drugs have been based on their local application. The systemic administration of
growth factors has been ruled out due to concerns about their safety. These
concerns are warranted. In addition, only a small proportion of systemically
administered drugs reach their intended target. Selective delivery of the drug to
the target tissue and use of functional protein domains capable of penetrating
cells and tissues could alleviate these problems in certain circumstances. We
will present in this review a novel approach utilizing unique molecular
fingerprints ("Zip/postal codes") in the vasculature of regenerating tissues that
allows target organ-specific delivery of systemically administered therapeutic
molecules by affinity-based physical targeting (using peptides or antibodies as
an "address tag") to injured tissues undergoing repair. The desired outcome of
targeted therapies is increased local accumulation and lower systemic
concentration of the therapeutic payload. We believe that the physical targeting
of systemically administered therapeutic molecules could be rapidly adapted in
the field of regenerative medicine.
PMID- 26437401
TI - Identification and Validation of Aspartic Acid Semialdehyde Dehydrogenase as a
New Anti-Mycobacterium Tuberculosis Target.
AB - Aspartic acid semialdehyde dehydrogenase (ASADH) lies at the first branch point
in the essential aspartic acid biosynthetic pathway that is found in bacteria and
plants but is absent from animals. Mutations in the asadh gene encoding ASADH
produce an inactive enzyme, which is lethal. Therefore, in this study, we
investigated the hypothesis that ASADH represents a new anti-Mycobacterium
tuberculosis (MTB) target. An asadh promoter-replacement mutant MTB, designated
MTB::asadh, in which asadh gene expression is regulated by pristinamycin, was
constructed to investigate the physiological functions of ASADH in the host
bacteria. Bacterial growth was evaluated by monitoring OD600 and ASADH expression
was analyzed by Western blotting. The results showed that the growth and survival
of MTB::asadh was completely inhibited in the absence of the inducer
pristinamycin. Furthermore, the growth of the mutant was rigorously dependent on
the presence of the inducer in the medium. The starved mutant exhibited a marked
reduction (approximately 80%) in the cell wall materials compared to the wild
type, in addition to obvious morphological differences that were apparent in
scanning electron microscopy studies; however, with the addition of
pristinamycin, the cell wall contents and morphology similar to those of the wild
type strain were recovered. The starved mutant also exhibited almost no
pathogenicity in an in vitro model of infection using mouse macrophage J774A.1
cells. The mutant showed a concentration-dependent recovery of pathogenicity with
the addition of the inducer. These findings implicate ASADH as a promising target
for the development of novel anti-MTB drugs.
PMID- 26437402
TI - Streamlining the Pipeline for Generation of Recombinant Affinity Reagents by
Integrating the Affinity Maturation Step.
AB - Often when generating recombinant affinity reagents to a target, one singles out
an individual binder, constructs a secondary library of variants, and affinity
selects a tighter or more specific binder. To enhance the throughput of this
general approach, we have developed a more integrated strategy where the
"affinity maturation" step is part of the phage-display pipeline, rather than a
follow-on process. In our new schema, we perform two rounds of affinity
selection, followed by error-prone PCR on the pools of recovered clones,
generation of secondary libraries, and three additional rounds of affinity
selection, under conditions of off-rate competition. We demonstrate the utility
of this approach by generating low nanomolar fibronectin type III (FN3)
monobodies to five human proteins: ubiquitin-conjugating enzyme E2 R1 (CDC34),
COP9 signalosome complex subunit 5 (COPS5), mitogen-activated protein kinase
kinase 5 (MAP2K5), Splicing factor 3A subunit 1 (SF3A1) and ubiquitin carboxyl
terminal hydrolase 11 (USP11). The affinities of the resulting monobodies are
typically in the single-digit nanomolar range. We demonstrate the utility of two
binders by pulling down the targets from a spiked lysate of HeLa cells. This
integrated approach should be applicable to directed evolution of any phage
displayed affinity reagent scaffold.
PMID- 26437404
TI - Fully Integrated Biopotential Acquisition Analog Front-End IC.
AB - A biopotential acquisition analog front-end (AFE) integrated circuit (IC) is
presented. The biopotential AFE includes a capacitively coupled chopper
instrumentation amplifier (CCIA) to achieve low input referred noise (IRN) and to
block unwanted DC potential signals. A DC servo loop (DSL) is designed to
minimize the offset voltage in the chopper amplifier and low frequency
respiration artifacts. An AC coupled ripple rejection loop (RRL) is employed to
reduce ripple due to chopper stabilization. A capacitive impedance boosting loop
(CIBL) is designed to enhance the input impedance and common mode rejection ratio
(CMRR) without additional power consumption, even under an external electrode
mismatch. The AFE IC consists of two-stage CCIA that include three compensation
loops (DSL, RRL, and CIBL) at each CCIA stage. The biopotential AFE is fabricated
using a 0.18 MUm one polysilicon and six metal layers (1P6M) complementary metal
oxide semiconductor (CMOS) process. The core chip size of the AFE without
input/output (I/O) pads is 10.5 mm2. A fourth-order band-pass filter (BPF) with a
pass-band in the band-width from 1 Hz to 100 Hz was integrated to attenuate
unwanted signal and noise. The overall gain and band-width are reconfigurable by
using programmable capacitors. The IRN is measured to be 0.94 MUVRMS in the pass
band. The maximum amplifying gain of the pass-band was measured as 71.9 dB. The
CIBL enhances the CMRR from 57.9 dB to 67 dB at 60 Hz under electrode mismatch
conditions.
PMID- 26437403
TI - Genome Editing Using Mammalian Haploid Cells.
AB - Haploid cells are useful for studying gene functions because disruption of a
single allele can cause loss-of-function phenotypes. Recent success in generating
haploid embryonic stem cells (ESCs) in mice, rats, and monkeys provides a new
platform for simple genetic manipulation of the mammalian genome. Use of haploid
ESCs enhances the genome-editing potential of the CRISPR/Cas system. For example,
CRISPR/Cas was used in haploid ESCs to generate multiple knockouts and large
deletions at high efficiency. In addition, genome-wide screening is facilitated
by haploid cell lines containing gene knockout libraries.
PMID- 26437405
TI - Hyperbolic Positioning with Antenna Arrays and Multi-Channel Pseudolite for
Indoor Localization.
AB - A hyperbolic positioning method with antenna arrays consisting of proximately
located antennas and a multi-channel pseudolite is proposed in order to overcome
the problems of indoor positioning with conventional pseudolites (ground-based
GPS transmitters). A two-dimensional positioning experiment using actual devices
is conducted. The experimental result shows that the positioning accuracy varies
centimeter- to meter-level according to the geometric relation between the
pseudolite antennas and the receiver. It also shows that the bias error of the
carrier-phase difference observables is more serious than their random error.
Based on the size of the bias error of carrier-phase difference that is inverse
calculated from the experimental result, three-dimensional positioning
performance is evaluated by computer simulation. In addition, in the three
dimensional positioning scenario, an initial value convergence analysis of the
non-linear least squares is conducted. Its result shows that initial values that
can converge to a right position exist at least under the proposed antenna setup.
The simulated values and evaluation methods introduced in this work can be
applied to various antenna setups; therefore, by using them, positioning
performance can be predicted in advance of installing an actual system.
PMID- 26437406
TI - A Context-Aware Model to Provide Positioning in Disaster Relief Scenarios.
AB - The effectiveness of the work performed during disaster relief efforts is highly
dependent on the coordination of activities conducted by the first responders
deployed in the affected area. Such coordination, in turn, depends on an
appropriate management of geo-referenced information. Therefore, enabling first
responders to count on positioning capabilities during these activities is vital
to increase the effectiveness of the response process. The positioning methods
used in this scenario must assume a lack of infrastructure-based communication
and electrical energy, which usually characterizes affected areas. Although
positioning systems such as the Global Positioning System (GPS) have been shown
to be useful, we cannot assume that all devices deployed in the area (or most of
them) will have positioning capabilities by themselves. Typically, many first
responders carry devices that are not capable of performing positioning on their
own, but that require such a service. In order to help increase the positioning
capability of first responders in disaster-affected areas, this paper presents a
context-aware positioning model that allows mobile devices to estimate their
position based on information gathered from their surroundings. The performance
of the proposed model was evaluated using simulations, and the obtained results
show that mobile devices without positioning capabilities were able to use the
model to estimate their position. Moreover, the accuracy of the positioning model
has been shown to be suitable for conducting most first response activities.
PMID- 26437408
TI - A High Performance LIA-Based Interface for Battery Powered Sensing Devices.
AB - This paper proposes a battery-compatible electronic interface based on a general
purpose lock-in amplifier (LIA) capable of recovering input signals up to the MHz
range. The core is a novel ASIC fabricated in 1.8 V 0.18 um CMOS technology,
which contains a dual-phase analog lock-in amplifier consisting of carefully
designed building blocks to allow configurability over a wide frequency range
while maintaining low power consumption. It operates using square input signals.
Hence, for battery-operated microcontrolled systems, where square reference and
exciting signals can be generated by the embedded microcontroller, the system
benefits from intrinsic advantages such as simplicity, versatility and reduction
in power and size. Experimental results confirm the signal recovery capability
with signal-to-noise power ratios down to -39 dB with relative errors below 0.07%
up to 1 MHz. Furthermore, the system has been successfully tested measuring the
response of a microcantilever-based resonant sensor, achieving similar results
with better power-bandwidth trade-off compared to other LIAs based on commercial
off-the-shelf (COTS) components and commercial LIA equipment.
PMID- 26437407
TI - Fiber-Optic Chemical Sensors and Fiber-Optic Bio-Sensors.
AB - This review summarizes principles and current stage of development of fiber-optic
chemical sensors (FOCS) and biosensors (FOBS). Fiber optic sensor (FOS) systems
use the ability of optical fibers (OF) to guide the light in the spectral range
from ultraviolet (UV) (180 nm) up to middle infrared (IR) (10 MUm) and modulation
of guided light by the parameters of the surrounding environment of the OF core.
The introduction of OF in the sensor systems has brought advantages such as
measurement in flammable and explosive environments, immunity to electrical
noises, miniaturization, geometrical flexibility, measurement of small sample
volumes, remote sensing in inaccessible sites or harsh environments and multi
sensing. The review comprises briefly the theory of OF elaborated for sensors,
techniques of fabrications and analytical results reached with fiber-optic
chemical and biological sensors.
PMID- 26437409
TI - Auto Regressive Moving Average (ARMA) Modeling Method for Gyro Random Noise Using
a Robust Kalman Filter.
AB - To solve the problem in which the conventional ARMA modeling methods for gyro
random noise require a large number of samples and converge slowly, an ARMA
modeling method using a robust Kalman filtering is developed. The ARMA model
parameters are employed as state arguments. Unknown time-varying estimators of
observation noise are used to achieve the estimated mean and variance of the
observation noise. Using the robust Kalman filtering, the ARMA model parameters
are estimated accurately. The developed ARMA modeling method has the advantages
of a rapid convergence and high accuracy. Thus, the required sample size is
reduced. It can be applied to modeling applications for gyro random noise in
which a fast and accurate ARMA modeling method is required.
PMID- 26437410
TI - Depth Estimation of Submerged Aquatic Vegetation in Clear Water Streams Using Low
Altitude Optical Remote Sensing.
AB - UAVs and other low-altitude remote sensing platforms are proving very useful
tools for remote sensing of river systems. Currently consumer grade cameras are
still the most commonly used sensors for this purpose. In particular, progress is
being made to obtain river bathymetry from the optical image data collected with
such cameras, using the strong attenuation of light in water. No studies have yet
applied this method to map submergence depth of aquatic vegetation, which has
rather different reflectance characteristics from river bed substrate. This study
therefore looked at the possibilities to use the optical image data to map
submerged aquatic vegetation (SAV) depth in shallow clear water streams. We first
applied the Optimal Band Ratio Analysis method (OBRA) of Legleiter et al. (2009)
to a dataset of spectral signatures from three macrophyte species in a clear
water stream. The results showed that for each species the ratio of certain
wavelengths were strongly associated with depth. A combined assessment of all
species resulted in equally strong associations, indicating that the effect of
spectral variation in vegetation is subsidiary to spectral variation due to depth
changes. Strongest associations (R2-values ranging from 0.67 to 0.90 for
different species) were found for combinations including one band in the near
infrared (NIR) region between 825 and 925 nm and one band in the visible light
region. Currently data of both high spatial and spectral resolution is not
commonly available to apply the OBRA results directly to image data for SAV depth
mapping. Instead a novel, low-cost data acquisition method was used to obtain six
band high spatial resolution image composites using a NIR sensitive DSLR camera.
A field dataset of SAV submergence depths was used to develop regression models
for the mapping of submergence depth from image pixel values. Band (combinations)
providing the best performing models (R2-values up to 0.77) corresponded with the
OBRA findings. A 10% error was achieved under sub-optimal data collection
conditions, which indicates that the method could be suitable for many SAV
mapping applications.
PMID- 26437411
TI - A Low Noise Amplifier for Neural Spike Recording Interfaces.
AB - This paper presents a Low Noise Amplifier (LNA) for neural spike recording
applications. The proposed topology, based on a capacitive feedback network using
a two-stage OTA, efficiently solves the triple trade-off between power, area and
noise. Additionally, this work introduces a novel transistor-level synthesis
methodology for LNAs tailored for the minimization of their noise efficiency
factor under area and noise constraints. The proposed LNA has been implemented in
a 130 nm CMOS technology and occupies 0.053 mm-sq. Experimental results show that
the LNA offers a noise efficiency factor of 2.16 and an input referred noise of
3.8 MUVrms for 1.2 V power supply. It provides a gain of 46 dB over a nominal
bandwidth of 192 Hz-7.4 kHz and consumes 1.92 MUW. The performance of the
proposed LNA has been validated through in vivo experiments with animal models.
PMID- 26437412
TI - GPS Cycle Slip Detection Considering Satellite Geometry Based on TDCP/INS
Integrated Navigation.
AB - This paper presents a means of carrier phase cycle slip detection for an inertial
aided global positioning system (GPS), which is based on consideration of the
satellite geometry. An integrated navigation solution incorporating a tightly
coupled time differenced carrier phase (TDCP) and inertial navigation system
(INS) is used to detect cycle slips. Cycle-slips are detected by comparing the
satellite-difference (SD) and time-difference (TD) carrier phase measurements
obtained from the GPS satellites with the range estimated by the integrated
navigation solution. Additionally the satellite geometry information effectively
improves the range estimation performance without a hardware upgrade. And the
covariance obtained from the TDCP/INS filter is used to compute the threshold for
determining cycle slip occurrence. A simulation and the results of a vehicle
based experiment verify the cycle slip detection performance of the proposed
algorithm.
PMID- 26437413
TI - Development of a Cost-Effective Airborne Remote Sensing System for Coastal
Monitoring.
AB - Coastal lands and nearshore marine areas are productive and rapidly changing
places. However, these areas face many environmental challenges related to
climate change and human-induced impacts. Space-borne remote sensing systems may
be restricted in monitoring these areas because of their spatial and temporal
resolutions. In situ measurements are also constrained from accessing the area
and obtaining wide-coverage data. In these respects, airborne remote sensing
sensors could be the most appropriate tools for monitoring these coastal areas.
In this study, a cost-effective airborne remote sensing system with synthetic
aperture radar and thermal infrared sensors was implemented to survey coastal
areas. Calibration techniques and geophysical model algorithms were developed for
the airborne system to observe the topography of intertidal flats, coastal sea
surface current, sea surface temperature, and submarine groundwater discharge.
PMID- 26437414
TI - Analysis of Surface Plasmon Resonance Curves with a Novel Sigmoid-Asymmetric
Fitting Algorithm.
AB - The present study introduces a novel curve-fitting algorithm for surface plasmon
resonance (SPR) curves using a self-constructed, wedge-shaped beam type angular
interrogation SPR spectroscopy technique. Previous fitting approaches such as
asymmetric and polynomial equations are still unsatisfactory for analyzing full
SPR curves and their use is limited to determining the resonance angle. In the
present study, we developed a sigmoid-asymmetric equation that provides excellent
curve-fitting for the whole SPR curve over a range of incident angles, including
regions of the critical angle and resonance angle. Regardless of the bulk fluid
type (i.e., water and air), the present sigmoid-asymmetric fitting exhibited
nearly perfect matching with a full SPR curve, whereas the asymmetric and
polynomial curve fitting methods did not. Because the present curve-fitting
sigmoid-asymmetric equation can determine the critical angle as well as the
resonance angle, the undesired effect caused by the bulk fluid refractive index
was excluded by subtracting the critical angle from the resonance angle in real
time. In conclusion, the proposed sigmoid-asymmetric curve-fitting algorithm for
SPR curves is widely applicable to various SPR measurements, while excluding the
effect of bulk fluids on the sensing layer.
PMID- 26437415
TI - Design and Performance Evaluation of a Dual Antenna Joint Carrier Tracking Loop.
AB - In order to track the carrier phases of Global Navigation Satellite Systems
(GNSS) signals in signal degraded environments, a dual antenna joint carrier
tracking loop is proposed and evaluated. This proposed tracking loop processes
inputs from two antennas, namely the master antenna and the slave antenna. The
master antenna captures signals in open-sky environments, while the slave antenna
capture signals in degraded environments. In this architecture, a Phase Lock Loop
(PLL) is adopted as a master loop to track the carrier phase of the open-sky
signals. The Doppler frequency estimated by this master loop is utilized to
assist weak carrier tracking in the slave loop. As both antennas experience
similar signal dynamics due to satellite motion and clock frequency variations, a
much narrower loop bandwidth and possibly a longer coherent integration can be
adopted to track the weak signals in slave channels, by utilizing the Doppler aid
from master channels. PLL tracking performance is affected by the satellite/user
dynamics, clock instability, and thermal noise. In this paper, their impacts on
the proposed phase tracking loop are analyzed and verified by both simulation and
field data. Theoretical analysis and experimental results show that the proposed
loop structure can track degraded signals (i.e., 18 dB-Hz) with a very narrow
loop bandwidth (i.e., 0.5 Hz) and a TCXO clock.
PMID- 26437416
TI - Does Laser Surgery Interfere with Optical Nerve Identification in Maxillofacial
Hard and Soft Tissue?--An Experimental Ex Vivo Study.
AB - The protection of sensitive structures (e.g., nerves) from iatrogenic damage is
of major importance when performing laser surgical procedures. Especially in the
head and neck area both function and esthetics can be affected to a great extent.
Despite its many benefits, the surgical utilization of a laser is therefore still
limited to superficial tissue ablation. A remote feedback system which guides the
laser in a tissue-specific way would provide a remedy. In this context, it has
been shown that nerval structures can be specifically recognized by their optical
diffuse reflectance spectra both before and after laser ablation. However, for a
translation of these findings to the actual laser ablation process, a nerve
protection within the laser pulse is of utmost significance. Thus, it was the aim
of the study to evaluate, if the process of Er:YAG laser surgery--which comes
with spray water cooling, angulation of the probe (60 degrees ) and optical
process emissions--interferes with optical tissue differentiation. For the first
time, no stable conditions but the ongoing process of laser tissue ablation was
examined. Therefore, six different tissue types (nerve, skin, muscle, fat,
cortical and cancellous bone) were acquired from 15 pig heads. Measurements were
performed during Er:YAG laser ablation. Diffuse reflectance spectra (4500,
wavelength range: 350-650 nm) where acquired. Principal component analysis (PCA)
and quadratic discriminant analysis (QDA) were calculated for classification
purposes. The clinical highly relevant differentiation between nerve and bone was
performed correctly with an AUC of 95.3% (cortial bone) respectively 92.4%
(cancellous bone). The identification of nerve tissue against the biological very
similar fat tissue yielded good results with an AUC value of 83.4% (sensitivity:
72.3%, specificity: of 82.3%). This clearly demonstrates that nerve
identification by diffuse reflectance spectroscopy works reliably in the ongoing
process of laser ablation in spite of the laser beam, spray water cooling and the
tissue alterations entailed by tissue laser ablation. This is an essential step
towards a clinical utilization.
PMID- 26437417
TI - Mitochondrial Dysfunction and Disturbed Coherence: Gate to Cancer.
AB - Continuous energy supply, a necessary condition for life, excites a state far
from thermodynamic equilibrium, in particular coherent electric polar vibrations
depending on water ordering in the cell. Disturbances in oxidative metabolism and
coherence are a central issue in cancer development. Oxidative metabolism may be
impaired by decreased pyruvate transfer to the mitochondrial matrix, either by
parasitic consumption and/or mitochondrial dysfunction. This can in turn lead to
disturbance in water molecules' ordering, diminished power, and coherence of the
electromagnetic field. In tumors with the Warburg (reverse Warburg) effect,
mitochondrial dysfunction affects cancer cells (fibroblasts associated with
cancer cells), and the electromagnetic field generated by microtubules in cancer
cells has low power (high power due to transport of energy-rich metabolites from
fibroblasts), disturbed coherence, and a shifted frequency spectrum according to
changed power. Therapeutic strategies restoring mitochondrial function may
trigger apoptosis in treated cells; yet, before this step is performed, induction
(inhibition) of pyruvate dehydrogenase kinases (phosphatases) may restore the
cancer state. In tumor tissues with the reverse Warburg effect, Caveolin-1 levels
should be restored and the transport of energy-rich metabolites interrupted to
cancer cells. In both cancer phenotypes, achieving permanently reversed
mitochondrial dysfunction with metabolic-modulating drugs may be an effective,
specific anti-cancer strategy.
PMID- 26437419
TI - Immunostimulative Activity of Low Molecular Weight Chitosans in RAW264.7
Macrophages.
AB - Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have
been reported to exert many biological activities, such as antioxidant and
antitumor effects. However, complex and molecular weight dependent effects of
chitosan remain controversial and the mechanisms that mediate these complex
effects are still poorly defined. This study was carried out to investigate the
immunostimulative effect of different molecular weight chitosan in RAW264.7
macrophages. Our data suggested that two LMWCs (molecular weight of 3 kDa and 50
kDa) both possessed immunostimulative activity, which was dependent on dose and,
at the higher doses, also on the molecular weight. LMWCs could significantly
enhance the the pinocytic activity, and induce the production of tumor necrosis
factor alpha (TNF-alpha), interleukin 6 (IL-6), interferon-gamma (IFN-gamma),
nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in a molecular
weight and concentration-dependent manner. LMWCs were further showed to promote
the expression of the genes including iNOS, TNF-alpha. Taken together, our
findings suggested that LMWCs elicited significantly immunomodulatory response
through up-regulating mRNA expression of proinflammatory cytokines and activated
RAW264.7 macrophage in a molecular weight- and concentration-dependent manner.
PMID- 26437420
TI - Marine Carotenoids against Oxidative Stress: Effects on Human Health.
AB - Carotenoids are lipid-soluble pigments that are produced in some plants, algae,
fungi, and bacterial species, which accounts for their orange and yellow hues.
Carotenoids are powerful antioxidants thanks to their ability to quench singlet
oxygen, to be oxidized, to be isomerized, and to scavenge free radicals, which
plays a crucial role in the etiology of several diseases. Unusual marine
environments are associated with a great chemical diversity, resulting in novel
bioactive molecules. Thus, marine organisms may represent an important source of
novel biologically active substances for the development of therapeutics. In this
respect, various novel marine carotenoids have recently been isolated from marine
organisms and displayed several utilizations as nutraceuticals and
pharmaceuticals. Marine carotenoids (astaxanthin, fucoxanthin, beta-carotene,
lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently
shown antioxidant properties in reducing oxidative stress markers. This review
aims to describe the role of marine carotenoids against oxidative stress and
their potential applications in preventing and treating inflammatory diseases.
PMID- 26437421
TI - Mycemycins A-E, New Dibenzoxazepinones Isolated from Two Different
Streptomycetes.
AB - Five new dibenzoxazepinone derivatives, mycemycins A-E (1-5), were isolated from
the ethanol extracts of mycelia of two different streptomycetes. 1 and 2 were
isolated from an acidic red soil-derived strain, Streptomyces sp. FXJ1.235, and 3
5 from a gntR gene-disrupted deep-sea strain named Streptomyces olivaceus
FXJ8.012Delta1741. The structures of mycemycins were elucidated by a combination
of spectroscopic analyses, including 1D- and 2D-NMR techniques.
PMID- 26437422
TI - Important Variables When Screening for Students at Suicidal Risk: Findings from
the French Cohort of the SEYLE Study.
AB - Due to early detection of mental ill-health being an important suicide preventive
strategy, the multi-centre EU funded "Saving and Empowering Young Lives in
Europe" (SEYLE) study compared three school-based mental health promotion
programs to a control group. In France, 1007 students with a mean age of 15.2
years were recruited from 20 randomly assigned schools. This paper explores the
French results of the SEYLE's two-stage screening program (ProfScreen) and of the
cross-program suicidal emergency procedure. Two-hundred-thirty-five ProfScreen
students were screened using 13 psychopathological and risk behaviour scales.
Students considered at risk because of a positive finding on one or more scales
were offered a clinical interview and, if necessary, referred for treatment. A
procedure for suicidal students (emergency cases) was set up to detect
emergencies in the whole cohort (n = 1007). Emergency cases were offered the same
clinical interview as the ProfScreen students. The interviewers documented their
reasons for referrals in a short report. 16,2% of the ProfScreen students
(38/235) were referred to treatment and 2,7% of the emergency cases (27/1007)
were also referred to treatment due to high suicidal risk. Frequent symptoms in
those students referred for evaluation were depression, alcohol misuse, non
suicidal self-injuries (NSSI), and suicidal behaviours. According to the
multivariate regression analysis of ProfScreen, the results show that the best
predictors for treatment referral were NSSI (OR 2.85), alcohol misuse (OR 2.80),
and depressive symptoms (OR 1.13). Analysis of the proportion for each scale of
students referred to treatment showed that poor social relationships (60%),
anxiety (50%), and suicidal behaviours (50%) generated the highest rate of
referrals. Qualitative analysis of clinician's motivations to refer a student to
mental health services revealed that depressive symptoms (51%), anxiety (38%),
suicidal behaviours (40%), and negative life events (35%) were the main reasons
for referrals. Thus, not only the classical psychopathological symptoms, such as
depression, anxiety, and suicidal behaviours, but also negative life events and
poor social relationships (especially isolation) motivate referrals for
treatment.
PMID- 26437423
TI - Early Substance Use Initiation and Suicide Ideation and Attempts among School
Aged Adolescents in Four Pacific Island Countries in Oceania.
AB - This study aimed to investigate the correlations between early initiation (<12
years) of smoking cigarettes, alcohol use, and drug use (cannabis) with suicidal
ideation and suicide attempts in school-aged adolescents in four Pacific Island
countries in Oceania. The sample included 6540 adolescents (<=13 to >=16 years
old) from Kiribati, Samoa, Solomon Islands, and Vanuatu. Bivariate and
multivariable analyses were conducted to assess the association between pre
adolescent substance use initiation and suicidal ideation and suicide attempts.
Results indicate a prevalence of 25.8% suicidal ideation in the past 12 months
(ranging from 17.2% in Vanuatu to 34.7% in Kiribati) and 34.9% suicide attempts
in the past 12 months (ranging from 23.5% in Vanuatu to 62.0% in Samoa). The
prevalence of early cigarette smoking initiation was 15.7%, early alcohol
initiation 13.8%, and early drug use initiation was 12.9%. Students who reported
pre-adolescent substance use initiation, compared with non-substance users, were
more likely reporting suicidal ideation and suicide attempts. The concurrent
initiation of cigarette smoking, alcohol, and drug use should be targeted in
early prevention programmes in order to prevent possible subsequent suicidal
behaviours.
PMID- 26437424
TI - Noise in the Sea and Its Impacts on Marine Organisms.
AB - With the growing utilization and exploration of the ocean, anthropogenic noise
increases significantly and gives rise to a new kind of pollution: noise
pollution. In this review, the source and the characteristics of noise in the
sea, the significance of sound to marine organisms, and the impacts of noise on
marine organisms are summarized. In general, the studies about the impact of
noise on marine organisms are mainly on adult fish and mammals, which account for
more than 50% and 20% of all the cases reported. Studies showed that
anthropogenic noise can cause auditory masking, leading to cochlear damage,
changes in individual and social behavior, altered metabolisms, hampered
population recruitment, and can subsequently affect the health and service
functions of marine ecosystems. However, since different sampling methodologies
and unstandarized measurements were used and the effects of noise on marine
organisms are dependent on the characteristics of the species and noise
investigated, it is difficult to compare the reported results. Moreover, the
scarcity of studies carried out with other species and with larval or juvenile
individuals severely constrains the present understanding of noise pollution. In
addition, further studies are needed to reveal in detail the causes for the
detected impacts.
PMID- 26437418
TI - Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer.
AB - The risk of onset of cancer is influenced by poorly controlled chronic
inflammatory processes. Inflammatory diseases related to cancer development
include inflammatory bowel disease, which can lead to colon cancer, or actinic
keratosis, associated with chronic exposure to ultraviolet light, which can
progress to squamous cell carcinoma. Chronic inflammatory states expose these
patients to a number of signals with tumorigenic effects, including nuclear
factor kappa B (NF-kappaB) and mitogen-activated protein kinases (MAPK)
activation, pro-inflammatory cytokines and prostaglandins release and ROS
production. In addition, the participation of inflammasomes, autophagy and
sirtuins has been demonstrated in pathological processes such as inflammation and
cancer. Chemoprevention consists in the use of drugs, vitamins, or nutritional
supplements to reduce the risk of developing or having a recurrence of cancer.
Numerous in vitro and animal studies have established the potential colon and
skin cancer chemopreventive properties of substances from marine environment,
including microalgae species and their products (carotenoids, fatty acids,
glycolipids, polysaccharides and proteins). This review summarizes the main
mechanisms of actions of these compounds in the chemoprevention of these cancers.
These actions include suppression of cell proliferation, induction of apoptosis,
stimulation of antimetastatic and antiangiogenic responses and increased
antioxidant and anti-inflammatory activity.
PMID- 26437425
TI - Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in
Chihuahua City, Mexico.
AB - Determining ionizing radiation in a geographic area serves to assess its effects
on a population's health. The aim of this study was to evaluate the spatial
distribution of the background environmental outdoor gamma dose rates in
Chihuahua City. This study also estimated the annual effective dose and the
lifetime cancer risks of the population of this city. To determine the outdoor
gamma dose rate in air, the annual effective dose and the lifetime cancer risk,
48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose
rate measurements were carried out by using a Geiger-Muller counter. Outdoor
gamma dose rates ranged from 113 to 310 nGy.h(-1). At the same sites, 48 soil
samples were taken to obtain the activity concentrations of (226)Ra, (232)Th and
(40)K and to calculate their terrestrial gamma dose rates. Radioisotope activity
concentrations were determined by gamma spectrometry. Calculated gamma dose rates
ranged from 56 to 193 nGy.h(-1). Results indicated that the lifetime effective
dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a
lifetime cancer risk of 0.001. In addition, the mean of the activity
concentrations in soil were 52, 73 and 1097 Bq.kg(-1), for (226)Ra, (232)Th and
(40)K, respectively. From the analysis, the spatial distribution of (232)Th,
(226)Ra and (40)K is to the north, to the north-center and to the south of city,
respectively. In conclusion, the natural background gamma dose received by the
inhabitants of Chihuahua City is high and mainly due to the geological
characteristics of the zone. From the radiological point of view, this kind of
study allows us to identify the importance of manmade environments, which are
often highly variable and difficult to characterize.
PMID- 26437426
TI - The Effects of Leptin on Breastfeeding Behaviour.
AB - Breastfed infants have a reduced risk of becoming overweight and/or obese later
in life. This protective effect has been partly attributed to leptin present in
breastmilk. This study investigated 24-h variations of skim milk leptin and its
relationship with breastmilk macronutrients and infant breastfeeding patterns.
Exclusive breastfeeding mothers of term singletons (n = 19; age 10 +/- 5 weeks)
collected pre- and post-feed breastmilk samples for every breastfeed over a 24-h
period and test-weighed their infants to determine milk intake at every
breastfeed over a 24-h period. Samples (n = 454) were analysed for leptin,
protein, lactose and fat content. Skim milk leptin concentration did not change
with feeding (p = 0.184). However, larger feed volumes (>105 g) were associated
with a decrease in post-feed leptin levels (p = 0.009). There was no relationship
between the change in leptin levels and change in protein (p = 0.313) or lactose
levels (p = 0.587) between pre- and post-feed milk, but there was a trend for a
positive association with changes in milk fat content (p = 0.056). Leptin
concentration significantly increased at night (p < 0.001) indicating a possible
24-h pattern. Leptin dose (ng) was not associated with the time between feeds (p
= 0.232). Further research should include analysis of whole breastmilk and other
breastmilk fractions to extend these findings.
PMID- 26437427
TI - Construction of Specific Primers for Rapid Detection of South African Exportable
Vegetable Macergens.
AB - Macergens are bacteria causing great damages to the parenchymatous tissues of
vegetable both on the field and in transit. To effectively and rapidly
investigate the diversity and distribution of these macergens, four specific
primers were designed by retrieving 16S rDNA sequences of pectolytic bacteria
from GenBank through the National Center for Biotechnology Information (NCBI).
These were aligned using ClusterW via BioEdit and primers were designed using
Primer3Plus platform. The size and primer location of each species and PCR
product size were accurately defined. For specificity enhancement, DNA template
of known macergens (Pectobacterium chrysanthermi) and fresh healthy vegetable
were used. These primers yielded expected size of approximately 1100 bp product
only when tested with known macergens and no amplicon with fresh healthy
vegetable was detected. Rapid detection of macergens in rotten vegetable samples
was then carried out using these primers. Nucleotide sequences of macergens
identified were deposited into the GenBank and were assigned accession numbers.
Hence, with these specific primers, macergens can be identified with minimal
quantities of the vegetable tissues using molecular techniques, for future use of
the quarantine section of the Agricultural Department of the country for quick
and rapid detection of macergens before exportation.
PMID- 26437428
TI - Isolation and Genome Characterization of the Virulent Staphylococcus aureus
Bacteriophage SA97.
AB - A novel bacteriophage that infects S. aureus, SA97, was isolated and
characterized. The phage SA97 belongs to the Siphoviridae family, and the cell
wall teichoic acid (WTA) was found to be a host receptor of the phage SA97.
Genome analysis revealed that SA97 contains 40,592 bp of DNA encoding 54
predicted open reading frames (ORFs), and none of these genes were related to
virulence or drug resistance. Although a few genes associated with lysogen
formation were detected in the phage SA97 genome, the phage SA97 produced neither
lysogen nor transductant in S. aureus. These results suggest that the phage SA97
may be a promising candidate for controlling S. aureus.
PMID- 26437429
TI - Vitamin D Deficiency Increases the Risk of Gestational Diabetes Mellitus: A Meta
Analysis of Observational Studies.
AB - The results investigating the relationship between vitamin D levels and
gestational diabetes mellitus (GDM) are inconsistent. Thus, we focused on
evaluating the association of vitamin D deficiency with GDM by conducting a meta
analysis of observed studies. A systematic literature search was conducted via
PubMed, MEDLINE, and Cochrane library to identify eligible studies before August
2015. The meta-analysis of 20 studies including 9209 participants showed that
women with vitamin D deficiency experienced a significantly increased risk for
developing GDM (odds ratio (OR) = 1.53; 95% confidence intervals (CI), 1.33,
1.75) with a little heterogeneity (I2 = 16.20%, p = 0.252). A noteworthy decrease
of 4.93 nmol/L (95% CI, -6.73, -3.14) in serum 25(OH)D was demonstrated in the
participants with GDM, and moderate heterogeneity was observed (I2 = 61.40%, p =
0.001). Subgroup analysis with study design showed that there were obvious
heterogeneities in nested case-control studies (I2 > 52.5%, p < 0.07).
Sensitivity analysis showed that exclusion of any single study did not materially
alter the overall combined effect. In summary, the evidence from this meta
analysis indicates a consistent association between vitamin D deficiency and an
increased risk of GDM. However, well-designed randomized controlled trials are
needed to elicit the clear effect of vitamin D supplementation on prevention of
GDM.
PMID- 26437431
TI - Measurement Issues in Anthropometric Measures of Limb Volume Change in Persons at
Risk for and Living with Lymphedema: A Reliability Study.
AB - Understanding whether a true change has occurred during the process of care is of
utmost importance in lymphedema management secondary to cancer treatments.
Decisions about when to order a garment, start an exercise program, and begin or
end therapy are based primarily on measurements of limb volume, based on
circumferences taken by physiotherapists using a flexible tape. This study aimed
to assess intra-rater and inter-rater reliability of measurements taken by
physiotherapists of legs and arms with and without lymphedema and to evaluate
whether there is a difference in reliability when measuring a healthy versus a
lymphedematous limb. The intra-rater reliability of arm and leg measurements by
trained physiotherapist is very high (scaled standard error of measurements
(SEMs) for an arm and a leg volume were 0.82% and 0.64%, respectively) and a cut
point of 1% scaled SEM may be recommended as a threshold for acceptable
reliability. Physiotherapists can rely on the same error when assessing
lymphedematous or healthy limbs. For those who work in teams and share patients,
practice is needed in synchronizing the measurements and regularly monitoring
their inter-rater reliability.
PMID- 26437430
TI - Impact of Chromatin on HIV Replication.
AB - Chromatin influences Human Immunodeficiency Virus (HIV) integration and
replication. This review highlights critical host factors that influence
chromatin structure and organization and that also impact HIV integration,
transcriptional regulation and latency. Furthermore, recent attempts to target
chromatin associated factors to reduce the HIV proviral load are discussed.
PMID- 26437432
TI - A Real-Time Magnetoencephalography Brain-Computer Interface Using Interactive 3D
Visualization and the Hadoop Ecosystem.
AB - Ecumenically, the fastest growing segment of Big Data is human biology-related
data and the annual data creation is on the order of zetabytes. The implications
are global across industries, of which the treatment of brain related illnesses
and trauma could see the most significant and immediate effects. The next
generation of health care IT and sensory devices are acquiring and storing
massive amounts of patient related data. An innovative Brain-Computer Interface
(BCI) for interactive 3D visualization is presented utilizing the Hadoop
Ecosystem for data analysis and storage. The BCI is an implementation of Bayesian
factor analysis algorithms that can distinguish distinct thought actions using
magneto encephalographic (MEG) brain signals. We have collected data on five
subjects yielding 90% positive performance in MEG mid- and post-movement
activity. We describe a driver that substitutes the actions of the BCI as mouse
button presses for real-time use in visual simulations. This process has been
added into a flight visualization demonstration. By thinking left or right, the
user experiences the aircraft turning in the chosen direction. The driver
components of the BCI can be compiled into any software and substitute a user's
intent for specific keyboard strikes or mouse button presses. The BCI's data
analytics OPEN ACCESS Brain. Sci. 2015, 5 420 of a subject's MEG brainwaves and
flight visualization performance are stored and analyzed using the Hadoop
Ecosystem as a quick retrieval data warehouse.
PMID- 26437433
TI - Interaction Study of Phospholipid Membranes with an N-Glucosylated beta-Turn
Peptide Structure Detecting Autoantibodies Biomarkers of Multiple Sclerosis.
AB - The interaction of lipid environments with the type I' beta-turn peptide
structure called CSF114 and its N-glucosylated form CSF114(Glc), previously
developed as a synthetic antigenic probe recognizing specific autoantibodies in a
subpopulation of multiple sclerosis patients' serum, was investigated by
fluorescence spectroscopy and electrochemical experiments using large unilamellar
vesicles, mercury supported lipid self-assembled monolayers (SAMs) and tethered
bilayer lipid membranes (tBLMs). The synthetic antigenic probe N-glucosylated
peptide CSF114(Glc) and its unglucosylated form interact with the polar heads of
lipid SAMs of dioleoylphosphatidylcholine at nonzero transmembrane potentials,
probably establishing a dual electrostatic interaction of the trimethylammonium
and phosphate groups of the phosphatidylcholine polar head with the Glu5 and His8
residues on the opposite ends of the CSF114(Glc) beta-turn encompassing residues
6-9. His8 protonation at pH 7 eliminates this dual interaction. CSF114(Glc) is
adsorbed on top of SAMs of mixtures of dioleoylphosphatidylcholine with
sphingomyelin, an important component of myelin, whose proteins are hypothesized
to undergo an aberrant N-glucosylation triggering the autoimmune response.
Incorporation of the type I' beta-turn peptide structure CSF114 into lipid SAMs
by potential scans of electrochemical impedance spectroscopy induces defects
causing a slight permeabilization toward cadmium ions. The N-glucopeptide
CSF114(Glc) does not affect tBLMs to a detectable extent.
PMID- 26437434
TI - Cancer Metabolism and Drug Resistance.
AB - Metabolic alterations, driven by genetic and epigenetic factors, have long been
known to be associated with the etiology of cancer. Furthermore, accumulating
evidence suggest that cancer metabolism is intimately linked to drug resistance,
which is currently one of the most important challenges in cancer treatment.
Altered metabolic pathways help cancer cells to proliferate at a rate higher than
normal, adapt to nutrient limited conditions, and develop drug resistance
phenotypes. Application of systems biology, boosted by recent advancement of
novel high-throughput technologies to obtain cancer-associated, transcriptomic,
proteomic and metabolomic data, is expected to make a significant contribution to
our understanding of metabolic properties related to malignancy. Indeed, despite
being at a very early stage, quantitative data obtained from the omics platforms
and through applications of (13)C metabolic flux analysis (MFA) in in vitro
studies, researchers have already began to gain insight into the complex
metabolic mechanisms of cancer, paving the way for selection of molecular targets
for therapeutic interventions. In this review, we discuss some of the major
findings associated with the metabolic pathways in cancer cells and also discuss
new evidences and achievements on specific metabolic enzyme targets and target
directed small molecules that can potentially be used as anti-cancer drugs.
PMID- 26437436
TI - New Insights into the Biological Role of Mammalian ADARs; the RNA Editing
Proteins.
AB - The ADAR proteins deaminate adenosine to inosine in double-stranded RNA which is
one of the most abundant modifications present in mammalian RNA. Inosine can have
a profound effect on the RNAs that are edited, not only changing the base-pairing
properties, but can also result in recoding, as inosine behaves as if it were
guanosine. In mammals there are three ADAR proteins and two ADAR-related proteins
(ADAD) expressed. All have a very similar modular structure; however, both their
expression and biological function differ significantly. Only two of the ADAR
proteins have enzymatic activity. However, both ADAR and ADAD proteins possess
the ability to bind double-strand RNA. Mutations in ADARs have been associated
with many diseases ranging from cancer, innate immunity to neurological
disorders. Here, we will discuss in detail the domain structure of mammalian
ADARs, the effects of RNA editing, and the role of ADARs in human diseases.
PMID- 26437437
TI - RNA-Binding Proteins in the Regulation of miRNA Activity: A Focus on Neuronal
Functions.
AB - Posttranscriptional modifications of messenger RNAs (mRNAs) are key processes in
the fine-tuning of cellular homeostasis. Two major actors in this scenario are
RNA binding proteins (RBPs) and microRNAs (miRNAs) that together play important
roles in the biogenesis, turnover, translation and localization of mRNAs. This
review will highlight recent advances in the understanding of the role of RBPs in
the regulation of the maturation and the function of miRNAs. The interplay
between miRNAs and RBPs is discussed specifically in the context of neuronal
development and function.
PMID- 26437435
TI - 4-Hydroxy-nonenal-A Bioactive Lipid Peroxidation Product.
AB - This review on recent research advances of the lipid peroxidation product 4
hydroxy-nonenal (HNE) has four major topics: I. the formation of HNE in various
organs and tissues, II. the diverse biochemical reactions with Michael adduct
formation as the most prominent one, III. the endogenous targets of HNE,
primarily peptides and proteins (here the mechanisms of covalent adduct formation
are described and the (patho-) physiological consequences discussed), and IV. the
metabolism of HNE leading to a great number of degradation products, some of
which are excreted in urine and may serve as non-invasive biomarkers of oxidative
stress.
PMID- 26437438
TI - The Role of the COP9 Signalosome and Neddylation in DNA Damage Signaling and
Repair.
AB - The maintenance of genomic integrity is an important process in organisms as
failure to sense and repair damaged DNA can result in a variety of diseases.
Eukaryotic cells have developed complex DNA repair response (DDR) mechanisms to
accurately sense and repair damaged DNA. Post-translational modifications by
ubiquitin and ubiquitin-like proteins, such as SUMO and NEDD8, have roles in
coordinating the progression of DDR. Proteins in the neddylation pathway have
also been linked to regulating DDR. Of interest is the COP9 signalosome (CSN), a
multi-subunit metalloprotease present in eukaryotes that removes NEDD8 from
cullins and regulates the activity of cullin-RING ubiquitin ligases (CRLs). This
in turn regulates the stability and turnover of a host of CRL-targeted proteins,
some of which have established roles in DDR. This review will summarize the
current knowledge on the role of the CSN and neddylation in DNA repair.
PMID- 26437439
TI - Rho GTPases: Novel Players in the Regulation of the DNA Damage Response?
AB - The Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the family of
Ras-homologous small GTPases. It is well characterized as a membrane-bound signal
transducing molecule that is involved in the regulation of cell motility and
adhesion as well as cell cycle progression, mitosis, cell death and gene
expression. Rac1 also adjusts cellular responses to genotoxic stress by
regulating the activity of stress kinases, including c-Jun-N-terminal
kinase/stress-activated protein kinase (JNK/SAPK) and p38 kinases as well as
related transcription factors. Apart from being found on the inner side of the
outer cell membrane and in the cytosol, Rac1 has also been detected inside the
nucleus. Different lines of evidence indicate that genotoxin-induced DNA damage
is able to activate nuclear Rac1. The exact mechanisms involved and the
biological consequences, however, are unclear. The data available so far indicate
that Rac1 might integrate DNA damage independent and DNA damage dependent
cellular stress responses following genotoxin treatment, thereby coordinating
mechanisms of the DNA damage response (DDR) that are related to DNA repair,
survival and cell death.
PMID- 26437441
TI - Molecular Process Producing Oncogene Fusion in Lung Cancer Cells by Illegitimate
Repair of DNA Double-Strand Breaks.
AB - Constitutive activation of oncogenes by fusion to partner genes, caused by
chromosome translocation and inversion, is a critical genetic event driving lung
carcinogenesis. Fusions of the tyrosine kinase genes ALK (anaplastic lymphoma
kinase), ROS1 (c-ros oncogene 1), or RET (rearranged during transfection) occur
in 1%-5% of lung adenocarcinomas (LADCs) and their products constitute
therapeutic targets for kinase inhibitory drugs. Interestingly, ALK, RET, and
ROS1 fusions occur preferentially in LADCs of never- and light-smokers,
suggesting that the molecular mechanisms that cause these rearrangements are
smoking-independent. In this study, using previously reported next generation
LADC genome sequencing data of the breakpoint junction structures of chromosome
rearrangements that cause oncogenic fusions in human cancer cells, we employed
the structures of breakpoint junctions of ALK, RET, and ROS1 fusions in 41 LADC
cases as "traces" to deduce the molecular processes of chromosome rearrangements
caused by DNA double-strand breaks (DSBs) and illegitimate joining. We found that
gene fusion was produced by illegitimate repair of DSBs at unspecified sites in
genomic regions of a few kb through DNA synthesis-dependent or -independent end
joining pathways, according to DSB type. This information will assist in the
understanding of how oncogene fusions are generated and which etiological factors
trigger them.
PMID- 26437440
TI - Physicochemical Properties of Ion Pairs of Biological Macromolecules.
AB - Ion pairs (also known as salt bridges) of electrostatically interacting cationic
and anionic moieties are important for proteins and nucleic acids to perform
their function. Although numerous three-dimensional structures show ion pairs at
functionally important sites of biological macromolecules and their complexes,
the physicochemical properties of the ion pairs are not well understood. Crystal
structures typically show a single state for each ion pair. However, recent
studies have revealed the dynamic nature of the ion pairs of the biological
macromolecules. Biomolecular ion pairs undergo dynamic transitions between
distinct states in which the charged moieties are either in direct contact or
separated by water. This dynamic behavior is reasonable in light of the
fundamental concepts that were established for small ions over the last century.
In this review, we introduce the physicochemical concepts relevant to the ion
pairs and provide an overview of the recent advancement in biophysical research
on the ion pairs of biological macromolecules.
PMID- 26437445
TI - Estimating Sustainable Live-Coral Harvest at Kamiali Wildlife Management Area,
Papua New Guinea.
AB - Live coral is harvested throughout the Indo-West Pacific to make lime, used in
the consumption of the world's fourth-most consumed drug, betel nut. Coral
harvesting is an environmental concern; however, because lime-making is one of
the few sources of income in some areas of Papua New Guinea (PNG), the practice
is unlikely to stop. To better manage coral harvest, we used standard fishery
yield methods to generate sustainable-harvest guidelines for corymbose Acropora
species found on the reef flat and crest at Lababia, PNG. We constructed a yield
curve (weight-specific net annual-dry-weight production) by: 1) describing the
allometric relationship between colony size and dry weight, and using that
relationship to estimate the dry weight of Acropora colonies in situ; 2)
estimating annual growth of Acropora colonies by estimating in situ, and
describing the relationship between, colony dry weight at the beginning and end
of one year; and 3) conducting belt-transect surveys to describe weight
frequencies and ultimately to predict annual weight change per square meter for
each weight class. Reef habitat covers a total 2,467,550 m2 at Lababia and
produces an estimated 248,397 kg/y (dry weight) of corymbose Acropora, of which
203,897 kg is produced on the reef flat/crest. We conservatively estimate that
30,706.6 kg of whole, dry, corymbose, Acropora can be sustainably harvested from
the reef flat/crest habitat each year provided each culled colony weighs at least
1805 g when dry (or is at least 46 cm along its major axis). Artisanal lime
makers convert 24.8% of whole-colony weight into marketable lime, thus we
estimate 7615.2 g of lime can be sustainably produced annually from corymbose
Acropora. This value incorporates several safety margins, and should lead to
proper management of live coral harvest. Importantly, the guideline recognizes
village rights to exploit its marine resources, is consistent with village needs
for income, and balances an equally strong village desire to conserve its marine
resources for future generations.
PMID- 26437443
TI - MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo
pathway.
AB - The Hippo pathway plays a central role in tissue homoeostasis, and its
dysregulation contributes to tumorigenesis. Core components of the Hippo pathway
include a kinase cascade of MST1/2 and LATS1/2 and the transcription co
activators YAP/TAZ. In response to stimulation, LATS1/2 phosphorylate and inhibit
YAP/TAZ, the main effectors of the Hippo pathway. Accumulating evidence suggests
that MST1/2 are not required for the regulation of YAP/TAZ. Here we show that
deletion of LATS1/2 but not MST1/2 abolishes YAP/TAZ phosphorylation. We have
identified MAP4K family members--Drosophila Happyhour homologues MAP4K1/2/3 and
Misshapen homologues MAP4K4/6/7-as direct LATS1/2-activating kinases. Combined
deletion of MAP4Ks and MST1/2, but neither alone, suppresses phosphorylation of
LATS1/2 and YAP/TAZ in response to a wide range of signals. Our results
demonstrate that MAP4Ks act in parallel to and are partially redundant with
MST1/2 in the regulation of LATS1/2 and YAP/TAZ, and establish MAP4Ks as
components of the expanded Hippo pathway.
PMID- 26437444
TI - Interleukin-23 Facilitates Thyroid Cancer Cell Migration and Invasion by
Inhibiting SOCS4 Expression via MicroRNA-25.
AB - Interleukin-23 (IL-23) is a conventional proinflammatory cytokine that plays a
role in tumor progression by inducing inflammation in the tumor microenvironment.
However, the role of IL-23 in thyroid cancer migration and invasion remains
unclear. In the present study, we observed that the treatment with IL-23, induced
migration and invasion in human thyroid cancer cells. Additional data demonstrate
that SOCS4 negatively regulates IL-23-mediated migration and invasion. On
investigating the mechanisms involved in IL-23 mediated migration and invasion,
we observed that miR-25 promotes the migration and invasion of thyroid cancer
cells by directly binding to the 3'-UTR of SOCS4 that leads to the inhibition of
SOCS4. In addition, we also demonstrated that IL-23 increases miR-25 expression
levels, and overexpressed miR-25 is involved in IL-23-associated SOCS4 inhibition
and cell migration and invasion. Together, our data suggest that IL-23 induces
migration and invasion in thyroid cancer cells by mediating the miR-25/SOCS4
signaling pathway.
PMID- 26437442
TI - Potential Role of the Gut/Liver/Lung Axis in Alcohol-Induced Tissue Pathology.
AB - Both Alcoholic Liver Disease (ALD) and alcohol-related susceptibility to acute
lung injury are estimated to account for the highest morbidity and mortality
related to chronic alcohol abuse and, thus, represent a focus of intense
investigation. In general, alcohol-induced derangements to both organs are
considered to be independent and are often evaluated separately. However, the
liver and lung share many general responses to damage, and specific responses to
alcohol exposure. For example, both organs possess resident macrophages that play
key roles in mediating the immune/inflammatory response. Additionally, alcohol
induced damage to both organs appears to involve oxidative stress that favors
tissue injury. Another mechanism that appears to be shared between the organs is
that inflammatory injury to both organs is enhanced by alcohol exposure. Lastly,
altered extracellular matrix (ECM) deposition appears to be a key step in disease
progression in both organs. Indeed, recent studies suggest that early subtle
changes in the ECM may predispose the target organ to an inflammatory insult. The
purpose of this chapter is to review the parallel mechanisms of liver and lung
injury in response to alcohol consumption. This chapter will also explore the
potential that these mechanisms are interdependent, as part of a gut-liver-lung
axis.
PMID- 26437446
TI - Hydroxyflutamide affects connexin 43 via the activation of PI3K/Akt-dependent
pathway but has no effect on the crosstalk between PI3K/Akt and ERK1/2 pathways
at the Raf-1 kinase level in primary rat Sertoli cells.
AB - We investigated the effects of 2-hydroxyflutamide (HF), an active metabolite of
the anti-androgen flutamide, on the activation of the phosphoinositide-3
kinase/protein kinase B (PI3K/Akt) in rat Sertoli cells. Sertoli cells, isolated
from 20-day-old rat testes, were cultured in vitro and treated with HF,
testosterone, or HF+testosterone. Studies by western blotting demonstrated that
HF inhibited the testosterone-mediated increase in c-Src activity (p<0.05). In
contrast, Akt phosphorylation was augmented within 5 min after HF treatment
(p<0.01). This effect was accompanied by a rapid upregulation in PTEN
phosphorylation (p<0.001). Despite no changes in Raf-1 phosphorylation, HF
increased extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation
(p<0.001), indicating that the effect of the anti-androgen on ERK1/2 was
independent of PI3K/Akt-pathway activation at this level. Since HF inhibited the
testosterone-mediated increase in c-Src activity, it is likely that activation of
both Akt and ERK1/2 occurred in a p-Src independent manner. Activation of
PI3K/Akt-pathway by HF resulted in the reduced level of Sertoli cell functional
marker, connexin 43 (p<0.01). Collectively, these data provide evidence that HF
rapidly and transiently affects the protein kinase-dependent signaling pathways,
acting both as an antagonist and agonist. Moreover, using testes of flutamide
treated rats for 7 days, we demonstrated that the anti-androgen can modulate the
protein kinase-dependent pathways in long term by enhancing Akt and ERK1/2
protein expression (p<0.05).
PMID- 26437448
TI - Impact of Michelangelo prosthetic hand: Findings from a crossover longitudinal
study.
AB - This work explores the functional and psychosocial impact of the multigrip
Michelangelo (M) prosthetic hand. Transradial myoelectric prosthesis users (6
men, median age: 47 y) participated in a crossover longitudinal study. A
multifactorial assessment protocol was applied before the application of M and
after 3 mo (functional assessment) and 6 mo (psychosocial assessment) of home
use. Functional assessment included both practical tests (i.e., Southampton Hand
Assessment Procedure [SHAP], Box and Blocks Test [BBT], and Minnesota Manual
Dexterity Test [MMDT]) and self-report functional scales. Psychosocial assessment
consisted of a clinical interview and a battery of self-report questionnaires
concerning current anxious-depressive symptoms and health-related quality of
life, body image concerns, adjustment and satisfaction with prosthesis, social
support, coping style, and personality. Increased manual dexterity was observed
after 3 mo based on improvements in the SHAP, BBT, and MMDT. Two important themes
emerged from the clinical interviews at the 6 mo follow-up: (1) the enhanced
functionality and (2) the "like a real hand" aspect of the M, which further
increased prosthesis integration to the Self. A few patients expressed concerns
about M dimension, noise, and weight. The M appeared to restore hand function and
natural appearance. The present findings provide preliminary evidence, and
additional studies are needed.
PMID- 26437447
TI - Discovery of a Novel Mutation (X8Del) Resulting in an 8-bp Deletion in the
Hepatitis B Virus X Gene Associated with Occult Infection in Korean Vaccinated
Individuals.
AB - Universal infantile hepatitis B virus (HBV) vaccination may lead to an increase
in vaccine escape variants, which may pose a threat to the long-term success of
massive vaccination. To determine the prevalence of occult infections in Korean
vaccinated individuals, 87 vaccinated subjects were screened for the presence of
HBV DNA using both the nested PCR protocol and the VERSANT HBV DNA 3.0 assay. The
mutation patterns of variants were analyzed in full-length HBV genome sequences.
Their HBsAg secretion and replication capacities were investigated using both in
vitro transient transfection and in vivo hydrodynamic injection. The presence of
HBV DNA was confirmed in 6 subjects (6.9%). All six variants had a common
mutation type (X8Del) composed of an 8-bp deletion in the C-terminal region of
the HBV X gene (HBxAg). Our in vitro and in vivo analyses using the full-length
HBV genome indicated that the X8Del HBxAg variant reduced the secretion of HBsAg
and HBV virions compared to the wild type. In conclusion, our data suggest that a
novel mutation (X8Del) may contribute to occult HBV infection in Korean
vaccinated individuals via a reduced secretion of HBsAg and virions, possibly by
compromising HBxAg's transacting capacity.
PMID- 26437450
TI - Prioritizing Clinically Relevant Copy Number Variation from Genetic Interactions
and Gene Function Data.
AB - It is becoming increasingly necessary to develop computerized methods for
identifying the few disease-causing variants from hundreds discovered in each
individual patient. This problem is especially relevant for Copy Number Variants
(CNVs), which can be cheaply interrogated via low-cost hybridization arrays
commonly used in clinical practice. We present a method to predict the disease
relevance of CNVs that combines functional context and clinical phenotype to
discover clinically harmful CNVs (and likely causative genes) in patients with a
variety of phenotypes. We compare several feature and gene weighing systems for
classifying both genes and CNVs. We combined the best performing methodologies
and parameters on over 2,500 Agilent CGH 180k Microarray CNVs derived from 140
patients. Our method achieved an F-score of 91.59%, with 87.08% precision and
97.00% recall. Our methods are freely available at https://github.com/compbio
UofT/cnv-prioritization. Our dataset is included with the supplementary
information.
PMID- 26437449
TI - Effect of a Multi-Dimensional and Inter-Sectoral Intervention on the Adherence of
Psychiatric Patients.
AB - BACKGROUND: In psychiatry, hospital stays and transitions to the ambulatory
sector are susceptible to major changes in drug therapy that lead to complex
medication regimens and common non-adherence among psychiatric patients. A multi
dimensional and inter-sectoral intervention is hypothesized to improve the
adherence of psychiatric patients to their pharmacotherapy. METHODS: 269 patients
from a German university hospital were included in a prospective, open, clinical
trial with consecutive control and intervention groups. Control patients (09/2012
03/2013) received usual care, whereas intervention patients (05/2013-12/2013)
underwent a program to enhance adherence during their stay and up to three months
after discharge. The program consisted of therapy simplification and
individualized patient education (multi-dimensional component) during the stay
and at discharge, as well as subsequent phone calls after discharge (inter
sectoral component). Adherence was measured by the "Medication Adherence Report
Scale" (MARS) and the "Drug Attitude Inventory" (DAI). RESULTS: The improvement
in the MARS score between admission and three months after discharge was 1.33
points (95% CI: 0.73-1.93) higher in the intervention group compared to controls.
In addition, the DAI score improved 1.93 points (95% CI: 1.15-2.72) more for
intervention patients. CONCLUSION: These two findings indicate significantly
higher medication adherence following the investigated multi-dimensional and
inter-sectoral program. TRIAL REGISTRATION: German Clinical Trials Register
DRKS00006358.
PMID- 26437451
TI - Black-white differences in cancer risk in Harare, Zimbabwe, during 1991-2010.
AB - Data from 20 years of cancer registration in Harare (Zimbabwe) are used to
investigate the risk of cancer in the white population of the city (of European
origin), relative to that in blacks (of African origin). In the absence of
information on the respective populations-at-risk, we calculated odds of each
major cancer among all cancers, and took the odds ratios of whites to blacks.
Some major differences reflect obvious phenotypic differences (the very high
incidence of skin cancer-melanoma and nonmelanoma--in the white population),
whereas others (high rates of liver cancer, Kaposi sarcoma and conjunctival
cancers in blacks) are the result of differences in exposure to infectious
agents. Of particular interest are cancers related to lifestyle factors, and how
the differences in risk are changing over time, as a result of evolving
lifestyles. Thus, the high risk of cancers of the esophagus and cervix uteri in
blacks (relative to whites) and colorectal cancers in whites show little change
over time. Conversely, the odds of breast cancer, on average four times higher in
whites than blacks, has shown a significant decrease in the differential over
time. Cancer of the prostate, with the odds initially (1991-1997) 15% higher in
whites had become 33% higher in blacks by 2004-2010.
PMID- 26437453
TI - Correction: DNA damage induces nuclear actin filament assembly by Formin-2 and
Spire-1/2 that promotes efficient DNA repair.
PMID- 26437452
TI - Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17
mediated emphysema.
AB - Chronic inhalation of cigarette smoke is the major cause of sterile inflammation
and pulmonary emphysema. The effect of carbon black (CB), a universal constituent
of smoke derived from the incomplete combustion of organic material, in smokers
and non-smokers is less known. In this study, we show that insoluble
nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells
(mDCs) from emphysematous lung and in CD11c(+) lung antigen presenting cells
(APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced
emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted
indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell
differentiation through double-stranded DNA break (DSB) and ASC-mediated
inflammasome assembly in phagocytes. Increasing the polarity or size of CB
mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and
emphysema and explains adverse health outcomes seen in smokers while implicating
the dangers of nCB exposure in non-smokers.
PMID- 26437455
TI - Reactive Charged Droplets for Reduction of Matrix Effects in Electrospray
Ionization Mass Spectrometry.
AB - A new quantitative contained-electrospray (ES) process is described here that
employs a movable ES emitter to control the reactivity of charged microdroplets
by varying their exposure time with acid vapor. The method allows elimination of
ion suppression effects caused by the presence of various surface active
compounds that coelute with the analyte. For mixtures, contained-ESI mass
spectrometric analysis produces relative ion intensities that reflect the true
concentrations of analytes in solution. The mechanism for this effect has been
elucidated and ascribed to the generation of fine initial droplets in the
presence of a high abundance of protons; together, these two factors eliminate
competition for charge and space during ion formation. Examples of analytes
tested include steroids, phospholipids, phosphopeptides, and sialylated glycans.
At least 1 order of magnitude improvement in detection limits, sensitivity, and
accuracy of detection was observed when compared to conventional electrospray.
PMID- 26437454
TI - Using Social Media for Actionable Disease Surveillance and Outbreak Management: A
Systematic Literature Review.
AB - OBJECTIVE: Research studies show that social media may be valuable tools in the
disease surveillance toolkit used for improving public health professionals'
ability to detect disease outbreaks faster than traditional methods and to
enhance outbreak response. A social media work group, consisting of surveillance
practitioners, academic researchers, and other subject matter experts convened by
the International Society for Disease Surveillance, conducted a systematic
primary literature review using the PRISMA framework to identify research,
published through February 2013, answering either of the following questions: Can
social media be integrated into disease surveillance practice and outbreak
management to support and improve public health?Can social media be used to
effectively target populations, specifically vulnerable populations, to test an
intervention and interact with a community to improve health outcomes?Examples of
social media included are Facebook, MySpace, microblogs (e.g., Twitter), blogs,
and discussion forums. For Question 1, 33 manuscripts were identified, starting
in 2009 with topics on Influenza-like Illnesses (n = 15), Infectious Diseases (n
= 6), Non-infectious Diseases (n = 4), Medication and Vaccines (n = 3), and Other
(n = 5). For Question 2, 32 manuscripts were identified, the first in 2000 with
topics on Health Risk Behaviors (n = 10), Infectious Diseases (n = 3), Non
infectious Diseases (n = 9), and Other (n = 10). CONCLUSIONS: The literature on
the use of social media to support public health practice has identified many
gaps and biases in current knowledge. Despite the potential for success
identified in exploratory studies, there are limited studies on interventions and
little use of social media in practice. However, information gleaned from the
articles demonstrates the effectiveness of social media in supporting and
improving public health and in identifying target populations for intervention. A
primary recommendation resulting from the review is to identify opportunities
that enable public health professionals to integrate social media analytics into
disease surveillance and outbreak management practice.
PMID- 26437457
TI - Morpho-syntactic processing of Arabic plurals after aphasia: dissecting lexical
meaning from morpho-syntax within word boundaries.
AB - Within the domain of inflectional morpho-syntax, differential processing of
regular and irregular forms has been found in healthy speakers and in aphasia.
One view assumes that irregular forms are retrieved as full entities, while
regular forms are compiled on-line. An alternative view holds that a single
mechanism oversees regular and irregular forms. Arabic offers an opportunity to
study this phenomenon, as Arabic nouns contain a consonantal root, delivering
lexical meaning, and a vocalic pattern, delivering syntactic information, such as
gender and number. The aim of this study is to investigate morpho-syntactic
processing of regular (sound) and irregular (broken) Arabic plurals in patients
with morpho-syntactic impairment. Three participants with acquired agrammatic
aphasia produced plural forms in a picture-naming task. We measured overall
response accuracy, then analysed lexical errors and morpho-syntactic errors,
separately. Error analysis revealed different patterns of morpho-syntactic errors
depending on the type of pluralization (sound vs broken). Omissions formed the
vast majority of errors in sound plurals, while substitution was the only error
mechanism that occurred in broken plurals. The dissociation was statistically
significant for retrieval of morpho-syntactic information (vocalic pattern) but
not for lexical meaning (consonantal root), suggesting that the participants'
selective impairment was an effect of the morpho-syntax of plurals. These results
suggest that irregular plurals forms are stored, while regular forms are derived.
The current findings support the findings from other languages and provide a new
analysis technique for data from languages with non-concatenative morpho-syntax.
PMID- 26437456
TI - Urban Market Gardening and Rodent-Borne Pathogenic Leptospira in Arid Zones: A
Case Study in Niamey, Niger.
AB - Leptospirosis essentially affects human following contact with rodent urine
contaminated water. As such, it was mainly found associated with rice culture,
recreational activities and flooding. This is also the reason why it has mainly
been investigated in temperate as well as warm and humid regions, while arid
zones have been only very occasionally monitored for this disease. In particular,
data for West African countries are extremely scarce. Here, we took advantage of
an extensive survey of urban rodents in Niamey, Niger, in order to look for
rodent-borne pathogenic Leptospira species presence and distribution across the
city. To do so, we used high throughput bacterial 16S-based metabarcoding, lipL32
gene-targeting RT-PCR, rrs gene sequencing and VNTR typing as well as GIS-based
multivariate spatial analysis. Our results show that leptospires seem absent from
the core city where usual Leptospira reservoir rodent species (namely R. rattus
and M. natalensis) are yet abundant. On the contrary, L. kirschneri was detected
in Arvicanthis niloticus and Cricetomys gambianus, two rodent species that are
restricted to irrigated cultures within the city. Moreover, the VNTR profiles
showed that rodent-borne leptospires in Niamey belong to previously undescribed
serovars. Altogether, our study points towards the importance of market gardening
in maintain and circulation of leptospirosis within Sahelian cities. In Africa,
irrigated urban agriculture constitutes a pivotal source of food supply,
especially in the context of the ongoing extensive urbanization of the continent.
With this in mind, we speculate that leptospirosis may represent a zoonotic
disease of concern also in arid regions that would deserve to be more rigorously
surveyed, especially in urban agricultural settings.
PMID- 26437458
TI - Penetrative Injury to the Face Resulting in Delayed Death After Rupture of a
Cavernous Sinus Aneurysm on the Contralateral Side.
AB - Delayed deaths after assault give rise to medicolegal issues such as whether the
assault was directly responsible, did it contribute or was it totally unrelated
to the death. We present the case of a patient who sustained penetrative trauma
to the face resulting in the formation of a contralateral, carotid-cavernous
fistula, which resulted in aneurysm formation, delayed rupture, and death. A
literature search failed to find a similar case.
PMID- 26437459
TI - Biogenic Amines and the Amino Acids GABA and Glutamate: Relationships with Pain
and Depression.
AB - Although it is well known that there is a high degree of comorbidity between
chronic pain and mood and anxiety disorders, the mechanisms involved in these co
occurrences are not clear. It appears that numerous neurotransmitters and
neuromodulators are involved, and this chapter focuses on the monoamine
neurotransmitters noradrenaline, 5-hydroxytryptamine (5-HT, serotonin), and
dopamine and the amino acid neurotransmitters GABA (gamma-aminobutyric acid) and
glutamate in chronic pain and depression. Numerous preclinical and clinical
neurochemical, neuroanatomical, pharmacological and molecular biological studies
as well as clinical pharmacological treatment investigations implicate
noradrenaline, 5-HT and, to a lesser extent, dopamine in the etiology of pain and
depression. Similarly, preclinical and clinical studies on GABAergic and
glutamatergic mechanisms as well as reports on the actions of neuroactive
steroids suggest that GABA and glutamate play an important role in the etiology
of pain and depression and may contribute to comorbidity.
PMID- 26437460
TI - Predicting Neuroinflammation in Morphine Tolerance for Tolerance Therapy from
Immunostaining Images of Rat Spinal Cord.
AB - Long-term morphine treatment leads to tolerance which attenuates analgesic effect
and hampers clinical utilization. Recent studies have sought to reveal the
mechanism of opioid receptors and neuroinflammation by observing morphological
changes of cells in the rat spinal cord. This work proposes a high-content
screening (HCS) based computational method, HCS-Morph, for predicting
neuroinflammation in morphine tolerance to facilitate the development of
tolerance therapy using immunostaining images for astrocytes, microglia, and
neurons in the spinal cord. HCS-Morph first extracts numerous HCS-based features
of cellular phenotypes. Next, an inheritable bi-objective genetic algorithm is
used to identify a minimal set of features by maximizing the prediction accuracy
of neuroinflammation. Finally, a mathematic model using a support vector machine
with the identified features is established to predict drug-treated images to
assess the effects of tolerance therapy. The dataset consists of 15 saline
controls (1 MUl/h), 15 morphine-tolerant rats (15 MUg/h), and 10 rats receiving a
co-infusion of morphine (15 MUg/h) and gabapentin (15 MUg/h, Sigma). The three
individual models of astrocytes, microglia, and neurons for predicting
neuroinflammation yielded respective Jackknife test accuracies of 96.67%, 90.00%,
and 86.67% on the 30 rats, and respective independent test accuracies of 100%,
90%, and 60% on the 10 co-infused rats. The experimental results suggest that
neuroinflammation activity expresses more predominantly in astrocytes and
microglia than in neuron cells. The set of features for predicting
neuroinflammation from images of astrocytes comprises mean cell intensity, total
cell area, and second-order geometric moment (relating to cell distribution),
relevant to cell communication, cell extension, and cell migration, respectively.
The present investigation provides the first evidence for the role of gabapentin
in the attenuation of morphine tolerance from phenotypic changes of astrocytes
and microglia. Based on neuroinflammation prediction, the proposed computer-aided
image diagnosis system can greatly facilitate the development of tolerance
therapy with anti-inflammatory drugs.
PMID- 26437461
TI - Risk of Demyelinating Diseases in the Central Nervous System in Patients With
Inflammatory Bowel Disease Treated With Tumor Necrosis Factor Inhibitors.
PMID- 26437464
TI - Snoring-Induced Vibratory Angioedema.
AB - BACKGROUND: Vibratory angioedema (VA) is a rare physical urticaria, with symptoms
of itching and swelling of the skin or mucosa when it is exposed to vibration.
Avoidance of vibration is the best way to manage this condition. This case report
will assist physicians to diagnose this rare condition. Here, a previously
unpublished potential successful treatment modality is being presented, with good
symptom control, along with some photographs taken during an acute attack. A
literature review points towards potential undiagnosed cases. CASE REPORT: A 70
year-old woman had multiple emergency department visits for tongue and throat
swelling over 3 years. The episodes always happened at night. Detailed history
elicited some episodes of itching and swelling of hands when driving as well as
significant snoring while sleeping. Physical examination was unremarkable except
for morbid obesity. Complement factor 4 and C1esterase inhibitor level were
within normal limits. A tentative diagnosis of angioedema induced by
oropharyngeal vibration from snoring was made. A sleep study confirmed sleep
apnea with severe snoring. After CPAP (continuous positive airway pressure)
treatment, she had successful symptom control. CONCLUSIONS: Snoring-induced VA is
very likely an under-diagnosed condition in the community. The typical history is
the key to the diagnosis. This condition could be confirmed by vibration test or
by the resolution of symptoms with elimination of vibration. Effective symptom
control is possible by avoidance of oropharyngeal vibration from snoring with the
administration of CPAP therapy, making it a potential novel indication for this
condition.
PMID- 26437463
TI - Development of a Radiolabeled Peptide-Based Probe Targeting MT1-MMP for Breast
Cancer Detection.
AB - Breast cancer is one of the most frequent and aggressive primary tumors among
women of all races. Matrix metalloproteinase (MMPs), a family of zinc- and
calcium-dependent secreted or membrane anchored endopeptidases, is overexpressed
in varieties of diseases including breast cancer. Therefore, noninvasive
visualization and quantification of MMP in vivo are of great interest in basic
research and clinical application for breast cancer early diagnosis. Herein, we
developed a 99mTc labeled membrane type I matrix metalloproteinase (MT1-MMP)
specific binding peptide, [99mTc]-(HYNIC-AF7p)(tricine)(TPPTS), for in vivo
detection of MDA-MB-231 breast tumor by single photon emission computed
tomography (SPECT). [99mTc]-(HYNIC-AF7p)(tricine)(TPPTS) demonstrated nice
biostability and high MT1-MMP binding affinity in vitro and in vivo. Tumor-to
muscle ratio was found to reach to the highest (4.17+/-0.49) at 2 hour after
intravenously administration of [99mTc]-(HYNIC-AF7P)(tricine)(TPPTS) into MDA-MB
231 tumor bearing mice. Overall, [99mTc]-(HYNIC-AF7P)(tricine)(TPPTS)
demonstrated great potential for MT1-MMP targeted detection in vivo and it would
be a promising molecular imaging probe that are probably beneficial to breast
cancer early diagnoses.
PMID- 26437462
TI - Familial Dysautonomia (FD) Human Embryonic Stem Cell Derived PNS Neurons Reveal
that Synaptic Vesicular and Neuronal Transport Genes Are Directly or Indirectly
Affected by IKBKAP Downregulation.
AB - A splicing mutation in the IKBKAP gene causes Familial Dysautonomia (FD),
affecting the IKAP protein expression levels and proper development and function
of the peripheral nervous system (PNS). Here we found new molecular insights for
the IKAP role and the impact of the FD mutation in the human PNS lineage by using
a novel and unique human embryonic stem cell (hESC) line homozygous to the FD
mutation originated by pre implantation genetic diagnosis (PGD) analysis. We
found that IKBKAP downregulation during PNS differentiation affects normal
migration in FD-hESC derived neural crest cells (NCC) while at later stages the
PNS neurons show reduced intracellular colocalization between vesicular proteins
and IKAP. Comparative wide transcriptome analysis of FD and WT hESC-derived
neurons together with the analysis of human brains from FD and WT 12 weeks old
embryos and experimental validation of the results confirmed that synaptic
vesicular and neuronal transport genes are directly or indirectly affected by
IKBKAP downregulation in FD neurons. Moreover we show that kinetin (a drug that
corrects IKBKAP alternative splicing) promotes the recovery of IKAP expression
and these IKAP functional associated genes identified in the study. Altogether,
these results support the view that IKAP might be a vesicular like protein that
might be involved in neuronal transport in hESC derived PNS neurons. This
function seems to be mostly affected in FD-hESC derived PNS neurons probably
reflecting some PNS neuronal dysfunction observed in FD.
PMID- 26437466
TI - Reply to the Editorial published in this issue on breastfeeding and ECC.
PMID- 26437465
TI - Effect of smoke-free legislation on perinatal and child health: a systematic
review and meta-analysis.
PMID- 26437467
TI - Reply to the Editorial published in issue 2/2005 on nutrition and dentistry.
PMID- 26437468
TI - [Proceeding of 44th annual meeting of the Japanese Society of
Neuropsychopharmacology. Nagoya, Japan. November 20-22, 2014. Abstracts].
PMID- 26437469
TI - [The patient-user-citizen revolution continues].
PMID- 26437470
TI - On Fifty-Plus Shades of graying Patients and Their Needs for Special Dentists.
PMID- 26437471
TI - Age and Frailty in Prosthodontics.
PMID- 26437472
TI - [Abstracts of the 45th Eastern/Western Regional Meeting, Japanese Society of
Nephrology. 2015. Japan].
PMID- 26437474
TI - [Abstracts of the 99th Congress of the Japanese Society of Legal Medicine. June
10-12, 2015, Kouchi, Japan].
PMID- 26437473
TI - Erratum.
PMID- 26437475
TI - [Abstracts of the 27th Annual Meeting of the Japanese Society of Clinical
Toxicology. July 4, 2015. Kanazawa, Japan]].
PMID- 26437476
TI - [A Grand Lady and two self-made men: testimony of a patient-investigator].
AB - The psychological distress of a person, a parent in this case, can have very
significant impact on family dynamics and the fate of all family members. They
may become unwitting experts of mental health, by accompanying necessity and with
their own vulnerabilities, sometimes trying to understand misunderstanding. This
story is that of a patient-investigator who questioned the impact that mental
illness has had on his professional life and his career choices. Going back to
distant childhood memories, this exercise has proved to be an introspective work
or observation of an individual conscience by itself. The fruit of this
reflection is the story of a double conversion, spiritual and scientific, and
this attempt to find sense and meaning to this personal journey becomes a
socially engaged ethics of research in mental health and psychiatry.
PMID- 26437477
TI - [In Process Citation].
PMID- 26437478
TI - [In Process Citation].
PMID- 26437479
TI - [In Process Citation].
PMID- 26437480
TI - [In Process Citation].
PMID- 26437481
TI - Beyond the Walls: Moving To Population Health.
PMID- 26437482
TI - Strategies and Vision: Looking Back from 2015.
PMID- 26437483
TI - Expanded Business View Benefits Catholic Systems.
PMID- 26437484
TI - THE FUTURE HAS ARRIVED: Shared, Collaborative and Sustainable.
PMID- 26437485
TI - TODAY'S TRANSFORMATIONAL MISSION: Opportunity Abounds to Bring More People Better
Care.
PMID- 26437486
TI - How Collaboration Becomes Partnership.
PMID- 26437487
TI - INTERVIEW WITH KEVIN E. LOFTON: Umbrella of Approaches Keeps Focus on Growth.
PMID- 26437488
TI - Sustaining the Mission through Mergers, Alliances, Partnerships.
PMID- 26437489
TI - SPEAKING IN A UNIFIED VOICE: The Power of 'We'.
PMID- 26437490
TI - Catholic Identity and the Reshaping of Health Care.
PMID- 26437491
TI - Taking an Untraditional View of Partnerships.
PMID- 26437492
TI - Investment in Innovation Can Bring Transformative Change.
PMID- 26437494
TI - THE CHALLENGES OF PRECISION MEDICINE.
PMID- 26437493
TI - MISSION LEADER SUCCESSION PLANNING: What If We Acted as One Ministry?
PMID- 26437495
TI - Using the Voice of the Church.
PMID- 26437496
TI - CHILDHOOD OBESITY: Report from the First Round of CHNAs and Implementation
Strategies.
PMID- 26437497
TI - Physical effects of non-cavitated explorer probing on enamel smooth-surface
carious lesions.
AB - PURPOSE: To assess the physical effects of explorer probing on non-cavitated
smooth-surface enamel carious lesions. METHODS: Extracted teeth with white enamel
decalcification (ICDAS 2) were used. Indentations were made in decalcified and
non-decalcified regions with a #23 explorer using "scratch" or "poke" application
and 100g, 300g or 600g force. Specimens were imaged with SEM and polarizing light
microscopy. Indentation widths were measured digitally. Two-way ANOVA with pair
wise comparisons was used to assess interactions of force and enamel condition
(normal or carious) on indentation groove width. RESULTS: No or minimal effect
was seen on normal enamel surface morphology. For the decalcified regions,
defects were seen in SEM and polarizing light images. Findings included a smear
layer, open clefts, lateral debris and micro-fractures. Two-way ANOVA for effects
of force and enamel quality on mean groove width showed statistically significant
differences for both variables for all teeth tested.
PMID- 26437498
TI - Confirmation of efficacy in providing relief from the pain of dentin
hypersensitivity of an anhydrous dentifrice containing 0.454% with or without
stannous fluoride in an 8-week randomized clinical trial.
AB - PURPOSE: To compare the efficacy of an anhydrous dentifrice containing 0.454% w/w
stannous fluoride and a negative control dentifrice containing 1,000 ppm
fluoride, as sodium monofluorophosphate, at reducing dentin hypersensitivity over
8 weeks with twice-daily brushing. METHODS: This was a randomized, examiner
blind, parallel, two treatment group, stratified (by maximum baseline Schiff
sensitivity score), 8-week clinical study carried out at a single site in 119
healthy subjects with at least two sensitive teeth, who met all study criteria at
the screening and baseline visits. Clinical assessments of sensitivity to
evaporative (air) [with Schiff sensitivity score and visual analogue scale (VAS)]
and tactile (Yeaple probe) stimuli were employed to compare the efficacy of the
test dentifrice containing 0.454% w/w stannous fluoride to the negative control
dentifrice at reducing sensitivity after 4 and 8 weeks treatment. RESULTS: Of the
119 subjects randomized to study treatment, 113 completed the study. At 4 and 8
weeks, between treatment analyses found the test dentifrice to be significantly
better than the negative control dentifrice in relieving dentin hypersensitivity
for all measures (Schiff: P < 0.0001 at 4 and 8 weeks; VAS score: P = 0.0003 at 4
weeks, P < 0.0001 at 8 weeks; tactile threshold: P = 0.0138 at 4 weeks, P <
0.0001 at 8 weeks).
PMID- 26437499
TI - Gingival health benefits of essential oil, 0.075% cetylpyridinium chloride and
control mouthrinses: A 4-week randomized clinical study.
AB - PURPOSE: This randomized, single center, examiner-blind, controlled, parallel
group, 4-week clinical study compared the antiplaque/anti-gingivitis efficacy of
an essential oil (EO) containing mouthrinse versus a 0.075% cetylpyridinium
chloride (CPC) containing mouthrinse. A 5% hydroalcohol solution was included as
a control group. METHODS: 165 systemically healthy volunteers (18-72 years of
age), with mild to moderate plaque-related gingivitis were enrolled in this
clinical trial; 162 subjects completed the study. At baseline and 4-week visits,
subjects received an oral examination, gingivitis (MGI), gingival bleeding (BI)
and plaque (PI) assessments. Following randomization, subjects began rinsing with
20 mL of the assigned mouthrinse for 30 seconds, in conjunction with their usual
oral hygiene, twice daily for the duration of the study. RESULTS: All rinses were
well tolerated by the subjects. EO was statistically significantly superior to
CPC with a reduction in mean MGI of 5.9%, and in mean PI of 6.4%. Statistically
significant reductions in gingivitis, bleeding and plaque were observed for both
EO and CPC when compared to the negative control; mean MGI and mean PI were
reduced by 13.0% and 18.9% for EO and by 7.6% and 13.3% for CPC. EO also
statistically significantly reduced the proportion of gingival bleeding sites
compared to CPC by 7.6% (P = 0.012) and compared to control by 10.6% (P < 0.001).
For the post hoc sitewise analyses, at 4 weeks, the mean percentage of healthy
sites for EO, CPC and Control were 7.4%, 1.1% and 0.8%, respectively and the mean
percentage of virtually plaque free sites for EO, CPC and control were 5.4%, 3.8%
and 0.4% respectively. The mean percentages of more inflamed gingival sites for
EO, CPC and control were 20.4%, 26.2% and 45.7%, respectively. The mean
percentage of tooth surfaces with heavier accumulations of plaque (PI scores >=
3) was 50.9% for EO, 56.1% for CPC and 81.1% for control. Reduction of gingival
inflammation and dental plaque was statistically significantly superior for EO
compared to both 0.075% CPC and negative control. Both marketed antimicrobial
mouthrinses showed a beneficial result in gingival health and in reducing plaque
accumulation as early as 4 weeks.
PMID- 26437501
TI - Radiolucent halos beneath composite restorations do not justify restoration
replacement.
AB - PURPOSE: To determine the correlation between the presence of radiolucent areas
(RA) beneath composite restorations and gaps and remaining demineralized tissue
(RDT). METHODS: 50 extracted teeth (sound and carious) were studied. After caries
removal, cavities were filled. Artificial cavities were created and filled in the
sound teeth. Samples were sectioned and analyzed with stereomicroscopy. RESULTS:
Gap/RDT was observed in 38.9% [95% confidence interval (CI) =28.2-50.5] and 68.9%
(95% CI = 57-78.6) of sound and carious teeth, respectively, (P = 0.001). Gap/RDT
was associated with RA (P < 0.001). Sensitivity, specificity, predictive positive
values (PPV), predictive negative value, and accuracy for carious teeth were
77.1% (95% CI = 63.7-87.3), 54.5% (95% CI = 33.8-74.1), 78.7% (95% CI = 65.3-
88.7), 52.2% (95% CI = 32.1-71.7), and 70% (95% CI = 58.5-79.8), and for sound
teeth were 73.7% (95% CI = 62.9-82.6), 59.1% (95% CI = 47.0-70.4), 67.5% (95% CI
= 56.9-76.9), 66.1% (95% CI = 53.4-77.3), and 66.9% (95% CI = 58.9-74.3). Only
the PPV differed between the sound and carious teeth (P = 0.024).There was a
correlation between radiolucency and gap/RDT, but a high number of false
positives were found.
PMID- 26437500
TI - Does refurbishing composites lead to short-term effects or long-lasting
improvement?
AB - PURPOSE: To evaluate the clinical performance of refurbished resin composite
restorations compared to untreated (negative control) restorations over a period
of 10 years. METHODS: 26 subjects (having a total of 52 composite restorations)
were recruited. All restorations in the refurbished group showed clinical
features rated bravo according to modified USPHS criteria. Untreated restorations
were those that had been deemed acceptable (alpha or bravo rated); these were
used as controls. Two examiners performed assessments at baseline and during the
5th and 10th years after the intervention. Wilcoxon tests were performed for
within-group comparisons, Friedman tests were used for multiple within-group
comparisons, and Mann Whitney tests were used for between-groups comparisons.
Kaplan-Meier survival curves were calculated, and the Mantel-Cox test was used to
compare curves. P < 0.05 was considered statistically significant. RESULTS: In
both groups, 10-year scores were significantly different from baseline scores in
all clinical parameters except secondary caries. There were no statistically
significant differences in the survival analysis of groups (log-rank test, P =
0.376). Refurbishing treatment improved the anatomy, roughness, luster, and
marginal adaptation of restorations with a short-term effect, with most
properties rated acceptable after 10 years of clinical service. The clinical
characteristics were similar for all groups at the 10th year.
PMID- 26437502
TI - Influence of multi-step etch-and-rinse versus self-etch adhesive systems on the
post-operative sensitivity in medium-depth carious lesions: An in vivo study.
AB - PURPOSE: To evaluate the influence of a three-step etch-and-rinse versus a two
step self-etch adhesive system on immediate post-operative sensitivity. METHODS:
In total, 204 subjects with one posterior tooth affected by a primary carious
lesion were recruited. The subjects were randomly divided into two groups, based
on the two multi-step adhesive systems used: Group A (All Bond 3) and Group B
(Clearfil Protect Bond). The same skilled operator carried out the restorations
using a nano-hybrid composite (Venus Diamond) in oblique stratification. Each
increment was light-cured for 20 seconds with a LED lamp (Translux Power Blue).
Subjects received a three-level thermal sensitivity questionnaire for post
operative sensitivity ratings. The evaluations were recorded daily for 7 days.
Scores were analyzed using the McNemar test and postoperative trends were
analyzed with the Friedman test (P < 0.05). All (100%) enrolled subjects
completed the follow-up visits. There was no statistically significant difference
between the two groups in post-operative sensitivity trends. In both groups,
increased post-operative sensitivity was found at D1, which then decreased
significantly during the observation period. RESULTS: The results of this in vivo
study showed that both of the tested adhesives, etch-and-rinse or self-etch,
provided effective dentin sealing, preventing subjects from experiencing post
operative sensitivity in the treatment of medium-depth cavities.
PMID- 26437503
TI - Influence of colorant solutions in properties of indirect resin composites.
AB - PURPOSE: To evaluate the influence of colorant solutions on color stability and
surface roughness of indirect resin composites submitted to prior immersion in
mouthwashes. METHODS: Five brands of indirect resin composites were assessed:
Adoro, Resilab, Cristobal, Sinfony and Epricord. The specimens were immersed in
five different solutions (n = 10): four mouthwashes (Listerine, Oral-B, Plax,
Periogard) and artificial saliva (control). 60 hours after immersion in
mouthwashes, the specimens were exposed to coffee solution. Shade stability and
surface roughness were tested by a spectrophotometer and by a profilometer,
respectively. A three-way repeated-measures ANOVA was performed. Differences
between the values were compared by the Tukey-Kramer test (P < 0.05). RESULTS:
The majority of the specimens showed human-perceptible color change. Greater
color change was observed after immersion in coffee, except for Cristobal. The
color change was even higher for specimens previously immersed in mouthwashes.
The Epricord resin showed the lowest roughness value and the Cristobal showed the
highest value, regardless of the period. The highest roughness change occurred
after immersion in Listerine.
PMID- 26437505
TI - Shear bond strength of two adhesives to bovine dentin contaminated with various
astringents.
AB - PURPOSE: To investigate the in vitro shear bond strength of two adhesives to
bovine dentin contaminated with various astringents. METHODS: 120 adult bovine
incisors were collected and cut to obtain 240 specimens. The specimens were
randomly divided into a self-etch adhesive group (N = 120) and a total-etch
adhesive group (N = 120). Both of the groups were divided into the following six
subgroups: the non-contamination group and the contamination groups 25% Al2(SO4)3
(Orbat sensitive), 25% AlCl3 (Racestyptine), 10% AlCl3 (Roeko Gingiva Liquid),
15.5% Fe2(SO4)3 (Astringedent) and AlCl3 Paste (Astringent Retraction Paste, N =
20 in each subgroup). Each astringent was applied for 1 minute to the dentin
surface before rinsing with water spray for 20 seconds. The respective adhesive
was then applied according to the manufacturer's instructions. Two composite
cylinders were shaped with a mold, cured on the dentin surface of each specimen
and sheared off after 1 day and 1 week storage. The shear bond strengths (MPa)
were recorded and analyzed with ANOVA. Results: In the self-etching adhesive
group, all astringents showed negative effects on dentin bonding (P < 0.05).
Astringent contamination did not have a negative effect on dentin bonding in the
total-etch adhesive group (P > 0.05).
PMID- 26437504
TI - Application of ethanol improves the resin-dentin bond strength of a two-bottle,
self-etching primer-adhesive.
AB - PURPOSE: To investigate whether the application of ethanol to a two-step self
etching adhesive can improve its resin-dentin bond performance. METHODS: Four
different ethanol concentrations were added to the adhesive of Clearfil SE Bond
to create four ethanol primers (40, 60, 80 or 100% ethanol). 24 extracted third
molars were divided into four groups. Each group corresponded to one of the four
hydrophobic ethanol primer concentrations. The teeth in the control group were
bonded with Clearfil SE Bond according to the manufacturer's instructions. The
primed teeth in the experimental groups were treated with the ethanol primer
prior to application of the solvent-free adhesive. Microtensile bond strengths
(mTBS) were tested 24 hours after specimen preparation. Another 14 teeth were
bonded using the same methods to evaluate mTBS after 1 year. Nanoleakage was
evaluated under field-emission scanning electron microscopy before and after
aging. RESULTS: In the 24-hour group, the mTBS in the 60% ethanol/40% adhesive
primer group increased significantly (21.6%, P < 0.05) over the no ethanol
control. After 12-month water storage, the bond strength of that experimental
group was still higher than that of the control group (19.5%, P < 0.05). Before
aging, the nanoleakage was clearly seen in the control group but hardly any was
seen in the experimental group. After aging, the nanoleakage increase in the
experimental group was much less than that in the control group.
PMID- 26437506
TI - Short-term clinical performance of zirconia single crowns with different
framework designs: 3-year clinical trial.
AB - PURPOSE: The present prospective clinical study evaluated the influence of coping
design on the fracture resistance of CAD/CAM zirconia single crowns layered with
dedicated ceramics. METHODS: 56 subjects were provided with 90 zirconia single
crowns in posterior regions. Tooth preparations were standardized and the
abutment teeth were randomly distributed into three groups, according to three
different coping designs (flat design, FD; porcelain-fused-to-metal-like crowns,
PFM; anatomically-guided, AG). The zirconia cores were produced using a CAD/CAM
software and then were hand-layered with dedicated ceramics. All crowns were
cemented with a self-adhesive resin luting agent and the patients were recalled
for follow-up visits after 1 month, 6 months, 1, 2 and 3 years of clinical
service. The function, esthetics and marginal adaptation of the restorations were
evaluated. Statistical analyses were performed to evaluate survival and success
of the restorations. RESULTS: Success rates of 100% were reported in Group 2 and
Group 3 while the percentage was 80% in Group 1. Three chippings were noticed in
Group 1 (FD) and two crowns needed to be replaced after 3 years, resulting in a
survival rate of 93.3%. Group 2 and Group 3 had significantly higher 3-year
success rates than Group 1 (P < 0.05). Based on the present clinical results, the
following conclusions were drawn: the porcelain-fused-to-metal-like and the
anatomically-guided frameworks for zirconia single crowns performed better
clinically than the flat designed cores in posterior regions after 3 years;
standardized tooth preparations achieved even thicknesses of the bilayered
restorations; the proper support given to the veneering ceramic by the correct
design of the zirconia framework could significantly reduce the risk of chipping
during function.
PMID- 26437507
TI - Temperature changes in bulk-fill resin composite during photopolymerization.
AB - PURPOSE: To investigate the temperature changes at multiple sites within bulk
fill resin composites and in the pulp chamber during photopolymerization in the
tooth cavity. METHODS: Class 1 cavities (n = 5) prepared in extracted third
molars were filled with SureFil SDR Flow, a newly developed bulk-fill composite.
After securing the specimens in a water bath at 36.5 degrees C, eight
thermocouples were used to measure the temperature at the bottom center (BC),
middle center (MC), top center (TC), bottom edge (BE), middle edge (ME), and top
edge (TE) of the restoration; the pulpal aspect of the dentin (PD); and the
center of the curing light tip (CL) during photopolymerization. RESULTS: The
maximum temperature values (degrees C) differed among the measurement sites. TC
exhibited the greatest temperature increase (72.3 +/- 2.4), followed by MC, BC,
TE, TE, ME, CL, and BE. The lowest temperature was observed at PD (41.1 +/- 1.9).
The peak temperatures within the composite were observed during the early stage
of light-curing, while CL and PD exhibited the highest temperature at the end
stage of light-curing.
PMID- 26437509
TI - Mixed Beds. Beyond the Frontiers of Classical Chromatography for Proteins.
PMID- 26437510
TI - Mechanistic Studies of Chiral Discrimination in Polysaccharide Phases.
PMID- 26437511
TI - Chromatographic Separation and NMR An Integrated Approach in Pharmaceutical
Development.
AB - Over the past 10 years, major improvements in the performance of LC-NMR have been
realized. The addition of postcolumn SPE, advances in probe technology including
cryogenic probes and microcoil probes, improved solvent suppression pulse
sequences, and shielded magnets with better homogeneity have all contributed to
rapid advancements in this technology. Application of LC-NMR to problems in
pharmaceutical development has had a major impact on structure elucidation
studies. LC-NMR has been successfully applied to determine the structures of
degradation products, impurities, mixtures of compounds, and metabolites. Use of
stop flow techniques with LC-NMR experiments has been a critical means of
identifying unstable compounds and studying conformational kinetics. The
integration of SPE as an intermediate step between the LC unit and the NMR
spectrometer has vastly improved the power of the hyphenated technique in trace
analysis applications. Online postcolumn enrichment of chromatographic peaks by
SPE dramatically reduces the NMR acquisition times by allowing repeated
injections to be trapped onto the same cartridge or different cartridges. Because
protonated solvents can be easily removed with a drying procedure, solvents and
buffers may be freely chosen for maximizing chromatographic separation without
compromising NMR spectral quality. The compound of interest may then be eluted
from an SPE cartridge using deuterated organic solvent, which helps to reduce
dynamic range issues. When combined with cryogenically cooled microcapillary
probes, the sensitivity of the NMR signal increases about 10-fold over
conventional room temperature probes, enabling full structure characterization at
the microgram level. Heteronuclear experiments with concentrations previously
only possible in a limited number of cases have now become standard experiments.
The availability of HSQC and HMBC experiments and microcoil/cryogenic technology
opens the possibility of using LC-(SPE) NMR for the structural elucidation of
complete unknowns on a microgram scale. To enable significant future downscaling
beyond the current capabilities, improved performance of the LC-NMR interface and
improved SPE cartridge retention need to be addressed. In addition, the active
volume of the NMR flow cell or capillary tube will have to shrink along with the
corresponding detection coils in order not to lose filling factor. As the size of
the NMR probes become more efficient with respect to mass sensitivity, techniques
such as CE or capillary electrochromatography (CEC) may be interfaced more
successfully with NMR spectroscopy. Overall, the current state of the art in LC
NMR has demonstrated proven utility in a variety of applications. When combined
with SPE and cryotechnology, LC-NMR has become an extremely valuable tool for
mass limited samples, enabling structure elucidation without the need for
laborious serial isolation and purification procedures.
PMID- 26437512
TI - Principles of Online Comprehensive Multidimensional Liquid Chromatography.
PMID- 26437513
TI - Organic Monolith Column Technology for Capillary Liquid Chromatography.
PMID- 26437514
TI - A Brief History of Superficially Porous Particles.
PMID- 26437515
TI - The Hydrophobic-Subtraction Model of Reversed-Phase Column Selectivity.
PMID- 26437517
TI - Recent Developments and Applications in Nonlinear Reversed Phase Liquid
Chromatography.
PMID- 26437516
TI - Chromatographic Hydrophobicity Index (CHI).
PMID- 26437518
TI - [Tribute to Maurice Rochaix].
PMID- 26437519
TI - [Questions regarding secularism of the public hospital].
PMID- 26437520
TI - [Abandoned children at the general hospital of Laon, 1780-1789].
PMID- 26437521
TI - [Religious orders and hospitals of Seine-Maritime].
PMID- 26437522
TI - [Organizing the photography collection of the hospitals of Rouen].
PMID- 26437523
TI - [The general hospital of Rouen. Its origins and its architectural evolution from
the 17th to the 19th century].
PMID- 26437524
TI - [Communicable diseases and their impact on the Rouen Hospital architecture].
PMID- 26437525
TI - [From the Saint-Nicolas hospice to the central hospital of Haguenau: 1180-2012].
PMID- 26437526
TI - [Bicetre Hospital - the Valley Foundation, 1890-1919].
PMID- 26437527
TI - [A half century of interns in the hospitals of Bordeaux].
PMID- 26437528
TI - Comparison of Clinical Manifestations and Survival Outcomes between
Neuroendocrine Tumor and Squamous Cell Carcinoma of the Uterine Cervix: Results
from a Tertiary Center in Southern Thailand.
AB - OBJECTIVE: To study the clinical manifestations and survival outcomes of
neuroendocrine tumor of the uterine cervix (NTUC) and compare them with those of
squamous cell carcinoma (SCCA) MATERIAL AND METHOD: A case-control study was
conducted. In the study group, we included patients whose tumors were described
in the original pathology reports as NTUC. For the control group, we calculated
the sample size based on a formula according to survival rate. The ratio of cases
to controls was 1:4. Patients with a diagnosis of SCCA of the uterine cervix and
treated between January 2003 and December 2011 in Son gklanagarind Hospital were
included in the control group according to stage and year of NT UC diagnos is.
The patients 'characteristics, method of treatment, treatment outcomes, and
survival of the two groups were compared. The prognostic factors among patients
with NTUC were analyzed using the Cox regression. RESULTS: Of the 2,835 cervical
carcinoma cases studied, 44 (1.6%) were NTUC. NTUC patients had a lower mean age
at diagnosis, received more multimodality treatments, had a lower complete
response rate, a higher recurrence rate, and more distant metastasis than their
SCCA counterparts. A significantly lower 2-year and 5-year survival was detected
in NTUC compared with SCCA (62% and 52% vs. 97% and 85%, respectively, p < 0.01).
In the univariate analysis, the number of sexual partners, stage of disease,
surgery treatment, status of response, and site of recurrence predicted a poorer
overall survival in NTUC. However, these factors were not found to be
statistically significant prognostic factors on multivariate analysis.
CONCLUSION: A poorer treatment outcome and prognosis were found in NTUC compared
with SCCA. Moreover a poorer prognosis was observed in NTUC patients with an
advanced-stage disease, non-surgery treatment, progressive disease, and distant
metastasis recurrence than in those with SCCA patients. Multimodality treatments
should be considered in NTUC to improve survival. Additionally close monitoring
may be necessary in this group of patients.
PMID- 26437529
TI - Reducing Pain and Anxiety during Second Trimester Genetic Amniocentesis Using
Aromatic Therapy: A Randomized Trial.
AB - OBJECTIVE: To evaluate the benefit of aromatic therapy using menthol for decrease
pain perception during amniocentesis. MATERIAL AND METHOD: A prospective
randomized study was conducted to compare pain level between groups ofpregnant
women who underwent amniocentesis with and without aromatic therapy using
menthol. Visual analogue scale (VAS) was usedfor pain assessment. The
participants were askedfor their anticipated pain and anxiety level and level
ofpain before and immediately after the procedure. RESULTS: Three hundred
seventeen pregnant women were recruited into the present study, 158 in the
menthol group and 159 in the non-menthol group. Mean VAS score of the post
procedure pain and anxiety did not differ significantly between the two groups.
Mean VAS score of the anticipated pain influenced the mean VAS score of the pre
procedure anxiety and post-procedure pain and anxiety irrespective of the group.
Mean VAS score of the pre-procedure anxiety and post-procedure pain and anxiety
increased about 0.3 cm for each 1 cm of increasing mean VAS score of anticipated
pain. CONCLUSION: Aromatic therapy using menthol was not significantly effective
in reducing pain and anxiety during second trimester genetic amniocentesis.
PMID- 26437530
TI - Association between Socioeconomic Status and Major Risk Factors of Stroke: Thai
Epidemiologic Stroke (TES) Study.
AB - OBJECTIVE: To investigate the association of socioeconomic status (SES)
(education, personal income, and occupation) with four major risk factors of
stroke, those are diabetes, hypertension, hypercholesterolemia, and current
smoker MATERIAL AND METHOD: The Thai Epidemiologic Stroke Study is a community
based cohort study, which recruitedparticipants from the general population from
five geographic regions around the country. Cross-sectional baseline data of
19,997 (6,803 men and 13,194 women) participants, aged 45 to 80 years were
included in the present analysis. Multiple logistic regression analysis was used
to estimate association ofsocioeconomic indicators with the major risk factors of
stroke. RESULTS: SES was associated with a major risk factor of stroke. Among
three indicators ofsocioeconomic status, education was more consistently
associated with the risk factors than personal income and occupation,
particularly in women. Education significantly inversely associated with diabetes
(p = 0.015 in men and 0.002 in women, respectively), and current smoker in both
sexes (p < 0.001), and with hypertension in women (p = 0.011). By contrast,
education was significantly positively associated with hypercholesterolemia in
women (p < 0.001). CONCLUSION: The differences in the prevalence of the major
risk factors of stroke between SES groups were important, and should be
considered in the development ofpolicies or tailored strategies for prevention of
stroke.
PMID- 26437531
TI - Ramathibodi Language Development Questionnaire: A Newly Developed Screening Tool
for Detection of Delayed Language Development in Children Aged 18-30 Months.
AB - OBJECTIVE: To develop a parental questionnaire for screening children with
delayed language development in primary care settings. MATERIAL AND METHOD:
Ramathibodi Language Development (RLD) questionnaire was developed and completed
by groups of 40 typically developing children age 18 to 30 months old and 30
children with delayed language development. RESULTS: The mean score was
significantly lower in the delay language group (6.7 +/- 1.9), comparing with the
typically developing group (9.6 +/- 0.7). The optimal ROC curve cut-off score was
8 with corresponding sensitivity and specificity were 98% and 72%, respectively.
The corresponding area under the curve was 0.96 (95% CI = 0.92-0.99). CONCLUSION:
The RLD questionnaire was the promising language developmental screening
instrument that easily utilized in well-child examination settings.
PMID- 26437532
TI - Randomized Controlled Trial of Azithromycin versus Doxycycline or Chloramphenicol
for Treatment of Uncomplicated Pediatric Scrub Typhus.
AB - OBJECTIVE: To evaluate the efficacy and safety of azithromycinfor treatment of
uncomplicated pediatric scrub typhus. MATERIAL AND METHOD: A randomized
controlled trial was performed. We compared azithromycin with doxycycline or
chloramphenicol in uncomplicated pediatric scrub typhus from inpatient pediatric
department of Chiangrai Prachanukroh Hospital. The primary outcome was cure rate
at day 3. The secondary outcomes were timing to defervescence within 72 hours,
side effects, and relapsed rate. We compared data between both groups with
Fisher's exact test or Mann-Whitney U test, and failure rate was demonstrated by
Kaplan-Meier survival curve and Log-rank test. RESULTS: We included 57 patients,
ofwhom, 28 were assigned to doxycycline or chloramphenicol (control group) and 29
to azithromycin (study group). The baseline characteristics of both groups were
similar The cure rate was 85.7% in the doxycycline or chloramphenicol group, as
compared to 79.3% in the azithromycin group (p = 0.73), and a median time to
defervescence was 30 hours (IQR 21, 48) vs. 36 hours (IQR 20, 68) respectively (p
= 0.166). There was a little minor side effect in azithromycin group. No relapsed
was found in either groups. CONCLUSION: Azithromycin was as effective as
doxycycline or chloramphenicol in treatment of uncomplicated pediatric scrub
typhus.
PMID- 26437533
TI - The Profile of Pediatric Patients Visit Emergency Department at Urban University
Hospital in Thailand.
AB - BACKGROUND: There is an absence of data describing pediatric patients who visit
Emergency Department (ED) in Thailand. Therefore, this report creates a profile
of pediatric emergency room visit at a university hospital in Thailand. MATERIAL
AND METHOD: The retrospective data of the pediatric patient aged less than 15
years that visited ED at Ramathibodi Hospital, Mahidol University, Bangkok,
Thailand between fiscal year (FY) 2002 and 2011 were reviewed. The Electronic
Medical Record Tracking was extracted. Demographic characteristic, acuity level,
timing, and presumptive diagnosis were reviewed. RESULTS: During the 10 years of
the data collection, 122,037 pediatric patient visited ED, thus, approximately
12,000 visits per year Pediatric patients account for an average of 18% of
hospital patients. Medical condition accounted for 95.21% of the visits followed
by trauma at 4.77%, and death at 0.02%. The triage categorized patients into
critical, emergency, urgency, and non-emergency, consisting of 0.6% as critical
patients, 37.6% as emergency patients, 52.5% as acute illness, and 9.3% as non
emergency patients. The three most common diagnosis were upper respiratory tract
infection, acute febrile illness, and acute gastroenteritis. Patient usually
visited ED in the evening shift 44% (4 p.m. to midnight), followed by morning
shift 40% (8 a.m. to 4 p.m.), and overnight shift 16% (midnight to 8 a.m.). There
were two highest peaks of ED visit, in June, during the rainy season, and in
January, during the winter. CONCLUSION: Pediatric patients attending the
emergency service were mostly for medical conditions. Acute illnesses were the
major group ofpediatric patients. A small proportion of visits in ED were true
emergencies.
PMID- 26437534
TI - The Short Stem THA Provides Promising Results in Patients with Osteonecrosis of
the Femoral Head.
AB - BACKGROUND: The short stem prosthesis showed good results in patients with
primary osteoarthritis. However there were afew studies about the short stem
total hip arthroplasty (THA) in patients with osteonecrosis of thefemoral head
(ONFH). OBJECTIVE: To evaluate the clinical and radiographic results of the short
stem THA in patients with ONFH. The authors hypothesized that the short stem THA
would be a promising procedure for patients with ONFH. MATERIAL AND METHOD: The
authors reviewed 120 osteonecrotic hips in 93 patients who underwent THA with
Metha(r) short stem between November 2010 and February 2013. The appearance of
bone trabeculae development and radiolucent line was reviewed using Gruen's
classification. The Harris hip score (HHS) was recorded at 6, 12, 24, and 36
monthspostoperative for evaluating the clinical results. RESULTS: The mean age of
patients was 44.4 years (18-68) with the mean BMI of 22.7 (15.1-32.5, SD 3.5).
The average follow-up period was 29.2 months (20-47). The mean HHS was
significantly improved from 43.9 (22.7-74, SD 7.7) preoperatively to 97.7 (85.9
100, SD 2.7) at 6-month postoperatively (p < 0.01). The radiographic change
around the stems showed bone trabeculae development at zone 1 (77 cases, 64.2%),
2 (27 cases, 22.5%), 3 (106 cases, 88.3%), 6 (120 cases, 100%), and 7 (115 cases,
95.8%). There was one case (0.8%) of 5 mm subsidence and the radiolucent line was
observed in zone 1. There were six cases (5%) of intraoperativefemoralfractures
and were treated with cerclage wires with nofurther subsidence observed There was
one case (0.8%) of distal stem perforation that had stable bone ingrowth. No
revision was required. CONCLUSION: The clinical and radiographic results of the
short stem THA in patients with ONFH are generally satisfactory. Its design
enables preservation of the bone stock and the bone trabeculae appear to confirm
the assumption of proximal force transmission. The authors believe that the short
stem THA is a promising procedure for patients with ONFH.
PMID- 26437535
TI - The Changes in Cortisol Levels during Cardiac Surgery: A Randomized Double
Blinded Study between Two Induction Agents Etomidate and Thiopentone.
AB - OBJECTIVE: To study the changes in cortisol levels during and after cardiac
surgery after an inductive dose of either etomidate or thiopentone and their
consequences. MATERIAL AND METHOD: A prospective, randomized, double-blinded
study was conducted in 26 patients undergoing elective cardiac surgery. They
received either etomidate or thiopentone for induction. Serum cortisol levels
were measured preoperatively, and then at 2-, 4-, 8-, and 24-hour All of the
patients received standard anesthesia and surgery. The data also included
patients perioperative management and outcome. RESULTS: There is no difference in
patients' characteristics. The baseline plasma morning cortisols in the two
groups were comparable (11.7 +/- 7.5 mcg/dL in etomidate group vs. 12.0 +/- 8.2
mcg/dL in thiopentone group). In both groups, during surgery, the cortisol levels
rose to higher levels and reached peak levels at four to eight hours and related
to surgical stress. At all times, the etomidate group had lower cortisol levels
but only at 8-hour the etomidate group had significantly lower cortisol level
(39.9 +/- 14.2 vs. 65.9 +/- 20.0 mcg/dL). At 24 hours, in both groups, cortisol
levels were lower than at 8-hour but did not return to normal baseline levels.
There were no differences in the dose of inotropic use and ICU stay. However
surprisingly the etomidate group had shorter hospital stay. CONCLUSION: A single
dose of etomidate usedfor induction in elective cardiac patients can partially
and reversibly inhibit of the cortisol synthesis for, at least, 24 hours, but its
association with any hemodynamic consequences cannot be concluded. REGISTRATION:
ClinicalTrials.gov as NCT01495949.
PMID- 26437536
TI - The Montreal Cognitive Assessment as a Screening Tool for Preoperative Cognitive
Impairment in Geriatric Patients.
AB - OBJECTIVE: Study the prevalence of cognitive impairment using the Montreal
Cognitive Assessment (MoCA), its relationship to physiologic age-related change,
and the preoperative drugs used in geriatric patients. MATERIAL AND METHOD: At
the preoperative visit, the co-researchers invited 322 general/vascular patients
(190 male, 132 female) and 260 urological patients (220 male, 40 female) who met
the inclusion criteria and were scheduled for elective surgery to join the study.
They went for the MoCA interview, and their preoperative drugs used were recorded
in a medication reconciliation file. A cut-off score 24 or above was considered
normal. RESULTS: Ninety-two general/vascular and 126 urological patients had
taken drugs before admission, but those did not show any correlation with the
MoCA score. There were 231 and 91 general/vascular patients and 175 and 85
urological patients with formal education of less than six years and equal/more
than six years respectively. The 286 and 36 general/vascular patients and 212 and
48 urological patients posted scores of less than 24 and equal/more than 24
respectively. Gender and education correlated positively and significantly with
the score; however age proved negatively significant. CONCLUSION: The prevalence
of cognitive impairment featured highly in preoperative geriatric patients. The
gender age, and education but not preoperative drugs used affected cognitive
function.
PMID- 26437537
TI - Epidemiology of Age-Related Macular Degeneration among the Elderly Population in
Thailand.
AB - OBJECTIVE: To estimate the prevalence and associated factors of age-related
macular degeneration (AMD) in Thailand. MATERIAL AND METHOD: This cross-sectional
survey was undertaken in 2010. Five provinces were selected and people aged 50
years and over were invited for eye examination. Demographic and health behaviors
and data from eye examination equipment were registered. Ophthalmologists graded
AMD as early or late based on fundus color photograph and image from optical
coherence tomography. Logistic regressions were analyzed to establish
associationfactorsfor AMD. RESULTS: Of the 7,043 participants, AMD wasfound in
862 people (12.2%), with more than half (53.1%) found in both eyes. Most cases
(94.3%) were early dry, 1.8% early wet, 3.4% late dry, and 0.7% late wet AMD.
Factors positively associated with AMD were age (OR 1.03, 95% CI 1.02-1.04),
diabetes mellitus (OR 1.20, 95% CI 1.03-1.39), and consumption of yellow
vegetable (OR 2.32, 95% CI 1.23-4.39). Factors that conversely associated with
AMD were consumption of green vegetable (OR 0.51, 95% CI 0.33-0.79), physical
exercise (OR 0.67, 95% CI 0.51-0.87), high bloodpressure (OR 0.75,95% CI 0.63
0.89), and heavy drinking habit (OR 0.45, 95% CI 0.26-0.75). CONCLUSION: The
prevalence of AMD in Thai population age 50 and over was 12.2%. More than half
(53.1%) of the cases were found in both eyes, but few at severe stages. The
present study confirmed age and DM as positive associated factors, and green
vegetable, exercise as negative associated factors. Further research should
investigate the effects of hypertension, yellow vegetable, and alcohol drinking
on AMD.
PMID- 26437538
TI - Stability of Bevacizumab Divided in Multiple Doses for Intravitreal Injection.
AB - OBJECTIVE: To investigate the stability of bevacizumab in multiple doses divided
from a single-use vial for intravitreal injection after storage at 4 degrees C
for up to six months and under drug transfer condition in tropical climate.
MATERIAL AND METHOD: Five syringes (0.1 mL, 2.5 mg) of bevacizumab were withdrawn
each from five new bevacizumab single-use vials (4 mL, 100 mg) under sterile
technique. The concentration of bevacizumab in each syringe was measured at two
dilutions (2 x 10(6) and 4 x 10(6) fold) using enzyme-linked immunosorbent assay
at baseline and after storage at 4 degrees C for 1-, 3-, and 6-month. Each assay
was performed at least twice. To simulate the drug transfer condition,
bevacizumab was placed in a brown plastic bag and put in another transfer plastic
bag with an ice cube for 30 minutes prior to the assay at 1-, 3-, and 6-month.
RESULTS: The concentrations of bevacizumab (mean +/- standard deviation) at
baseline, 1-, 3-, and 6-month were 26.24 +/- 1.95, 25.43 +/- 3.80, 27.87 +/-
2.81, and 24.25 +/- 2.00 mg/mL, respectively. The lowest lower limit of 95%
confidence interval for the mean concentration was 23.32 mg/mL at 6-month
storage, which was 89% of the mean baseline concentration and considered to be
non-inferior to the baseline concentration. CONCLUSION: Bevacizumab in a single
use vial could be divided into multiple small doses for intravitreal injection
with sufficient stability when refrigerated at 4 degrees C for up to six months
and under the drug transfer condition in tropical climate.
PMID- 26437539
TI - Computerized Tomographic Angiography for Detection of Cerebral Vasospasm after
Ruptured Intracranial Aneurysm.
AB - OBJECTIVE: Digital subtraction angiography (DSA) is the gold standard to diagnose
cerebral vasospasm but it is usually not available due to lack of expertise and
proper equipment. The present study aimed to compare the diagnostic accuracy of
brain computerized tomographic angiography (CTA) in detecting cerebral vasospasm
after intracranial aneurysmal rupture. MATERIAL AND METHOD: Between January 2011
and October 2014, 20 patients who were suspected of cerebral vasospasm after
aneurysmal subarachnoid hemorrhage (SAH) were prospectively enrolled. All
patients underwent brain CTA andDSA within 24 hours after clinical onset
ofvasospasm. Separate reviewers independently reviewed the CTA and DSA. RESULTS:
Twenty patients were enrolled, including 7 males and 13 females. The patient
characteristics did not have any relationship to the incidence of cerebral
vasospasm. The CTA finding of vasospasm was well correlated to the DSA finding
(Kappa 0.793). Diagnostic accuracy and false negative of the CTA were 90% and 5%,
respectively. Sensitivity of the CTA was 94% and specificity was 100%. Positive
predictive value ofthe CTA was 100% and negative predictive value was 66%. The
vessels that showed the most correlation between the CTA and DSA findings were
left A1 (Kappa 0.684) and left A2 (Kappa 0.663) segments of anterior cerebral
artery, and left M1 (Kappa 0.503) segment of middle cerebral artery. Both CTA and
DSA can detect mild vasospasm (< 50% luminal stenosis) located proximal to the
circle of Willis. CONCLUSION: Compared to the DSA, the CTA can be used for
detecting cerebral vasospasm in patients with ruptured intracranial aneurysms
with high sensitivity, specificity, and diagnostic accuracy.
PMID- 26437540
TI - The Diagnosis of Acute Cholecystitis: Sensitivity of Sonography,
Cholescintigraphy and Computed Tomography.
AB - OBJECTIVE: To compare the sensitivity of sonographic, cholescintigraphic, and
computed tomographic examination of acute cholecystitis to the pathology result,
which is considered the Gold Standard. MATERIAL AND METHOD: A retrospective
analytic study was conducted among 412 patients, aged between 15 and 98 years,
who underwent cholecystectomy surgeries, and whose pathology results indicated
acute cholecystitis between July 2004 and May 2013. The sensitivity and the
differences between sensitivity of the three methods were calculated in all
patients. Complicated acute cholecystitis cases were analyzed separately.
RESULTS: The three methods demonstrated statistically significant differences in
sensitivity (p-value = 0.017), with the cholescintigraphy as the most sensitive
method (84.2%), followed by computed tomography (67.3%), and sonography (59.8%).
Concerning the samples with the pathology result indicating complicated acute
cholecystitis, computed tomography was statistically significantly more sensitive
than sonography in detecting acute cholecystitis, whether or not the
complications were identified (100% and 63.6%, respectively, with p-value =
0.0055). None of the patients with the pathology result of complicated acute
cholecystitis case was examined by cholescintigraphy, thus, no calculation was
possible. Regarding the ability to detect the complications of acute
cholecystitis, computed tomography had a sensitivity of 35.71% (5 in 14
patients), while sonographic examinations could not detect any of the
complications. CONCLUSION: Cholescintigraphy is a more sensitive method than
computed tomography and sonography, but the three methods have its own
advantages, disadvantages, and limitations, which must be consideredfor each
individual patient.
PMID- 26437541
TI - Clinicopathological Features and Prognostic Factors of Malignant Melanoma: A
Retrospective Analysis of Thai Patients in Ramathibodi Hospital.
AB - OBJECTIVE: To present the clinicopathological characteristics of cutaneous
melanoma in Thai patients and to define the possible clinicopathological
prognostic factors. MATERIAL AND METHOD: A retrospective study of primary
cutaneous melanoma in Thai patients in Ramathibodi Hospital between January 2007
and December 2012 was conducted. All medical records and skin biopsies were
reviewed for demographic data and histopathologicalfeatures. Univariate and
multivariate analysis for overall survival, and prognostic factors, according to
clinical and histopathological features were performed. RESULTS: Fourty-three
patients with pathologically confirmed primary cutaneous melanoma were identified
and reviewed. The median age of onset was 58 years, with male:female ratio was
1:1.05. Acral lentiginous melanoma (ALM) was the most common type (76.7%). The
majority of patients had clinical stage 11 (56.1%). Histologically, the median
tumor thickness was 2.9 mm, 88.2% had Clark's level IV and V, 47.1% were
ulcerated, and 76.5% had dermal mitotic rate of >= 1 mitoses/mm. The 5-year
overall survival rates was 38.3%. Univariate analysis demonstrated that clinical
stage IV Breslow's thickness of > 3 mm, and dermal mitotic rate of >= 3
mitoses/mm2 were bad prognostic factors. Multivariate analysis demonstrated that
advanced clinical staging (stage III and IV), Breslow's thickness of > 3 mm,
ulceration, palmoplantar or subungual site, and histologic subtype of ALM were
the independent risk factors for poor prognosis. CONCLUSION: Most patients with
cutaneous melanoma in Thai patients had the histologic subtype of ALM and were
diagnosed with locally advanced disease (stage II). The prognosis depends on
clinical staging, Breslow's thickness, ulceration, primary location of tumor and
histologic subtype.
PMID- 26437542
TI - Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC
SPECT/CT: A Rare Case Report.
AB - The authors reported an uncommon presentation of metastatic neuroendocrine
carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old
woman who, previously, had carcinoid tumor of left main bronchus and invasive
ductal carcinoma of the right breast. Later, the patient developed left breast
mass. Core needle biopsy of the mass revealed poorly differentiated invasive
ductal carcinoma. The disease remained stable for 12 years without any treatment
on that left breast (due to patient's rejection). On the later investigation
using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal
carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis
was confirmed by pathological examination after surgical excision. Multiple
metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones
were also depicted. Due to the good behavior of the disease, patient had been
doing well for eight months, without specific treatment. This report confirmed
the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of
neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be
in differential diagnosis for patient with breast mass together with history of
neuroendocrine tumor
PMID- 26437543
TI - [Constant Performance].
PMID- 26437545
TI - [Strategy for Determining the Appropriate Dose of Sugammadex with Monitoring
Train-of-four (TOF) Responses at the End of Surgery].
AB - BACKGROUND: Intraoperative monitoring of train-of-four (TOF) response is
recommended to avoid inadequate dose of muscle relaxant and its antagonist. We
have standardized monitoring of TOF response at the end of surgery in all the
patients undergoing general anesthesia with rocuronium since October 2013.
METHODS: TOF group comprised of 113 consecutive patients just after the
standardization and we investigated the relationship between the dose of
sugammadex and TOF count and also compared anesthetic factors in TOF group with
those in control group which included 104 consecutive patients just before the
standardization without TOF monitoring. RESULTS: Rate of the patients with TOF
count 4 in TOF group approximately reached 70% and mean TOF ratio resulted in
0.56 +/- 0.28. Mean dose of sugammadex in patients with TOF count 2-4 was 2.5 +/-
0.9 mg x kg(-1), while the dose in patients with TOF count 0-1 was 3.6 +/- 0.9 mg
x kg(-1) and 6 patients among 11 patients with TOF count 0 was given less than 4
mg x kg(-1) of sugammadex. The percentage of the patients given 200 mg of
sugammadex significantly decreased from 78% in control group to 48% in TOF group.
CONCLUSIONS: We conclude that standardization of TOF response at the end of
surgery reduces dose of sugammadex in patients with slight residual neuromuscular
block though the dose in patients under deep muscle relaxation seems to be
insufficient.
PMID- 26437544
TI - [The Interaction of Low-dose Droperidol, Propofol, and Sevoflurane on QTc
Prolongation].
AB - BACKGROUND: Droperidol is an effective antiemetic, but its use is limited because
of the warning of drug-induced QT prolongation. Some reports showed that low-dose
droperidol does not significantly probing QT interval. This study was aimed to
determine the effect of low-dose droperidol (1.25 and 2.5 mg) on QTc interval,
and the interaction among droperidol, propofol and sevoflurane. METHODS: Patients
received either 1.25 mg (group L : n = 25) or 2.5 mg (group H : n = 25)
droperidol, and fentanyl (3 MUg x kg(-1)) was administered 2.5 min later. One
minute after fentanyl administration, anesthesia was induced using propofol (1.5
mg x kg(-1)) and vecuronium. One minute after propofol administration,
sevoflurane (3%) was started. Tracheal intubation was performed 3 min after
propofol administration, and then sevoflurane was reduced to 1%. RESULTS:
Compared to baseline, the QTc interval in group L was unchanged by droperidol. In
group H, the QTc interval was significantly prolonged after droperidol injection,
but recovered after propofol injection. After tracheal intubation, QTc interval
was significantly prolonged in both groups. CONCLUSIONS: Droperidol's effect on
QTc prolongation was shown at the dose of 2.5 mg but not 1.25 mg. This
prolongation effect was offset by propofol, and was unchanged by sevoflurane.
PMID- 26437546
TI - [Risk Factors for Poor Prognosis after Emergency Surgery for Acute Abdomen].
AB - BACKGROUND: Risk factors associated with poor outcome were investigated in
patients receiving emergency surgery. METHODS: Patients' characteristics,
surgical information, postoperative complication and 30-days mortality were
reviewed in 226 adult consecutive patients undergoing emergency abdominal
surgery. Postoperative complication was defined as surgical site infection,
anastomotic leakage, intraperitoneal abscess and formation or requirement of
renal replacement therapy. Multivariate logistic regression was performed to
identify the parameters associated with 30-day mortality and postoperative
complication. RESULTS: Mortality rate was 7.1%. Complication occurred in 41.2%.
Multivariate logistic regression revealed surgical Apgar score (SAS) as
independent predictor of the death. SAS, duration of the surgery and preoperative
SOFA were identified as independent predictors of the complication. CONCLUSIONS:
SAS and preoperative SOFA are useful to predict poor prognosis after emergency
surgery due to acute abdomen.
PMID- 26437547
TI - [Incidence, Risk Factors, and Effects on Outcome of Postoperative Delirium in
Patients Undergoing Esophagectomy].
AB - BACKGROUND: Postoperative delirium (POD) is a common but serious complication
after major surgery. The aim of this study was to investigate the incidence and
effects on outcome of POD in esophagectomy patients, and to identify risk factors
for developing POD. METHODS: A retrospective medical record review was conducted
for all patients who had received esophagectomy for esophageal cancer during a
three-year period. RESULTS: In a total of 71 patients, the overall incidence of
POD was 20%. Multivariable regression analysis identified two independent risk
factors for POD: older age (70) and preoperative electrolyte abnormalities.
Patients with delirium had a higher incidence of respiratory complications and
longer hospital stays compared with the non-delirium patients. CONCLUSIONS: The
incidence of POD in patients undergoing esophagectomy is 20%. The risk factors of
POD are older age and preoperative electrolyte abnormalities. POD negatively
impacts postoperative respiratory complications and hospital stay.
PMID- 26437548
TI - [Transient Femoral Nerve Palsy after Ilioinguinal-Iliohypogastric Nerve Block:
Comparison of Ultrasound-guided and Landmark-based Techniques in Adult Inguinal
Hernia Surgery].
AB - BACKGROUND: Transient femoral nerve palsy (TFNP) is a well-known complication
associated with ilioinguinal-iliohypogastric nerve block (IINB). We compared the
incidence of TFNP after ultrasound-guided IINB and that after anatomical landmark
based IINB. METHODS: We reviewed medical records of adult patients (ASA-PS 1-3,
Age 21-87) who had received inguinal hernia surgery under general anesthesia and
LINB retrospectively. IINB was performed using 0.5% ropivacaine either by
ultrasound-guidance (US group, n = 16) or by landmark-based technique (LM group,
n =17). TFNP was defined as sensory loss in the anterior aspect of the thigh or
weakness of quadriceps femoris muscle in the nerve-blocked side. RESULTS: The
frequency of TFNP in US group (6%) was lower than that in LM group (41%) in the
post-anesthesia care unit (P = 0.019). TFNP symptom was resolved completely on
the morning after surgery. The incidence of severe-intermediate postoperative
pain and analgesic requirement were not different between the two groups.
CONCLUSIONS: This study revealed that ultrasound-guided technique is effective to
lower the incidence of TFNP after IINB in adult inguinal hernia surgery.
PMID- 26437549
TI - [Serratus-Intercostal Plane Block for Brest Surgery].
AB - BACKGROUND: Serratus-intercostal plane block (SIPB) is a novel ultrasound-guided
thoracic wall nerve block reported recently. We performed SIPB for perioperative
analgesia together with general anesthesia in patients undergoing partial
mastectomy. METHODS: We chose the patients with breast cancer of upper to lower
lateral quadrant or subareolar region. The patients received general anesthesia
followed by ultrasound-guided SIPB. The needle was introduced in the midaxillary
line at the level of the fourth or fifth rib. Under continuous ultrasound
guidance, we injected 30 ml of ropivacaine 0.375-0.5% between the serratus
anterior and the external intercostal muscles. RESULTS: After the partial
mastectomy, the area of sensory loss obtained by skin prick was extended from
five to six as the number of intercostal spaces. Analgesic effect was obtained
for 12 to 24 hours. The cephalad dermatomal paresthesia was T2. More than 20
patients received SIPB, and no one acquired the sensory loss at T1 of dermatomal
distribution. CONCLUSIONS: SIPB provides effective analgesia for breast surgery
of upper to lower lateral quadrant and/or subareolar region. However, it should
be administered with other additional analgesic agents when axillary dissection
is performed, because sensory loss of T1 is difficult to achieve.
PMID- 26437551
TI - [A Biphasic Anaphylactic Attack from Sugammadex with a Severe Second Attack].
AB - A 74-year-old man was scheduled for transurethral resection of the prostate under
general anesthesia. Anesthesia was induced by propofol, rocuronium, remifentanil
and maintained with sevoflurane. The operation was finished in 56 minutes without
trouble. After operation, sugammadex was administered, and after about 2 minutes,
redness, tachycardia, hypotension and itchiness appeared. Treatment was initiated
using steroids, adrenaline, and antihistamine upon diagnosis of anaphylaxis
caused by sugammadex. Reaction to the treatment was good and the general
condition improved to normal; however, the patient was moved to the intensive
care unit for follow-up observation. Furthermore, no upper respiratory tract
symptoms were observed during the follow-up along with no decline in SpO2. The
condition progressed without any particularly major abnormalities after entering
the intensive care unit; however, a sudden decline in blood pressure and dyspnea
occurred again 3 hours following entering the intensive care unit. These were
considered to be biphasic reactions due to anaphylaxis, and treatment was carried
out again with intravenous injection of adrenaline, steroids and inhalation of
beta-agonist. No symptoms were observed since and the patient was discharged from
the intensive care unit the following day.
PMID- 26437550
TI - [The Hemodynamics and Bispectral Index Score during Lower Abdominal Surgery under
Balanced Anesthesia with the Two Different Combination Doses of Desflurane and
Remifentanil].
AB - BACKGROUND: The purpose of this study was to examine the hemodynamics and
bispectral index score during lower abdominal surgery under balanced anesthesia
with the two different combination doses of desflurane and remifentanil. METHODS:
Twenty patients undergoing total hysterectomy were allocated into two groups; 1)
10 patients received 4.5% end-tidal concentration of desflurane combined with
remifentanil 0.125 MUg x kg(-1) x min(-1) (H group) and 2) 10 patients received
3.0% end-tidal concentration of desflurane combined with remifentanil 0.2 MUg x
kg(-1) X min(-1) (L group). Mean arterial pressure (MAP), heart rate (HR) and BIS
were recorded 5 times (on admission to operating room, immediately before
surgery, 5 minutes after the skin incision, at the moment of uterine extraction
and during retroperitoneal closure). RESULTS: MAP and HR during surgery did not
increase compared with those on admission to operating room, and BIS was
unchanged throughout the study in both two groups. CONCLUSIONS: The patients
could be anesthetized adequately during lower abdominal surgery under balanced
anesthesia with the two different combination doses of desflurane and
remifentanil.
PMID- 26437552
TI - [A Case of Repetitive Cardiac Arrest due to Coronary Vasospasm after Sugammadex
Administration].
AB - A 58-year-old man with no history of cardiac disease was scheduled for a cerebral
aneurysm clipping surgery. Anesthesia was administered with propofol, rocuronium,
fentanyl, and remifentanil. At the end of the surgery, extubation was performed 3
min after the administration of 200 mg sugammadex, along with a simultaneous
blood-pressure decrease with ST elevation on lead II. Cardiopulmonary
resuscitation was per- formed owing to the occurrence of lethal arrhythmia, and
the patient was successfully resuscitated. Subsequent emergent coronary
angiography revealed normal coronary arteries. Twelve days after the first
surgery, a tracheostomy was performed owing to persistent disturbance of
consciousness. Anesthesia was administered with sevoflurane, fentanyl, and
rocuronium. Sugammadex 200 mg was administered after the insertion of a tracheal
cannula, and 5 min later, the blood pressure were gradually decreased with ST
depression on lead V5. Finally, cardiopulmonary resuscitation was required, and
the patient recovered again. An acetylcholine provocation test performed later
showed positive results. We suspect sugammadex to be the cause of coronary
vasospasm, because the time courses of the two cardiac arrest episodes after
sugammadex administration were very similar. Therefore, clinicians should
consider sugammadex as one of the causative agents of cardiac arrest in the
operating room.
PMID- 26437553
TI - [Anesthesia Management for Primary Cleft Lip Closure in an Infant with Congenital
Total Length Complete Tracheal Rings].
AB - Complete tracheal ring causes congenital tracheal stenosis in neonates and
infants. We have to prevent further tracheal stenosis in perioperative period.
This is a case report of an infant with congenital tracheal stenosis due to
complete tracheal ring who underwent primary cleft lip closure under general
anesthesia. An 8 month-old boy was scheduled for bilateral cleft lip closure. His
first operation at two months was canceled because of unsuccessful intubation in
previous hospital. He came to our hospital to seek a second opinion. His CT scan
showed long segment stenosis of the trachea below glottis. The tracheobronchial
endoscopy showed complete tracheal rings 1.5 cm below glottis to the bifurcation.
Considering his aspiration episode, we decided to do the cleft lip closure
promptly after examinations. We chose an ID 3.0 mm RAE tracheal tube, which is
commercially narrowest We intubated 2 cm below glottis, and confirmed that the
tip did not touch narrowed trachea with endoscope. This tube was fixed in the
center of the mandible and packed with gauze. He was discharged on 8 POD without
complication. CT scan and its integrated 3 D image of the trachea were useful to
understand the approximate structure. However endoscopic examination allowed more
detailed structure-measurement below glottis.
PMID- 26437554
TI - [Rapid Sequence Intubation with the McGRATH MAC Videolaryngoscope in the Sitting
Position for a Patient with Restricted Mouth Opening].
AB - Here we report successful rapid-sequence inubation with the McGRATH MAC
videolaryngscope (McGRATH) in the face to face sitting position for a patient
with severe ileus and restricted mouse opening. A 46-year-old woman with advanced
bladder cancer had developed ileus. Ileus tube and octreotide did not relieve her
symptoms, and emergency colostomy was planned. Due to the invasion of cancer to
the spine and interior of the pelvis, she could not keep supine position and
always kept sitting position. We decided to perform rapid-sequence intubation in
the sitting position. First an anesthesiologist stood at face to face position to
the patients, and the second anesthesiologist kept the head of the patient from
the cranial side. After thiamylal and fentanyl administration, cricoid pressure
was applied by the third anesthesiologist. Under the guide of the McGRATH's
monitor, we could successfully insert the 7.0 mm internal diameter tracheal tube
with a stylet uneventfully in the face to face sitting position.
PMID- 26437555
TI - [Reexpansion Pulmonary Edema during Emergency Surgery in a Patient with
Spontaneous Hemopneumothorax].
AB - A 43-year-old male patient with spontaneous hemopneumothorax of the right lung
underwent emergency video-assisted thoracoscopic surgery for drainage, hemostasis
and bullae resection. Fifteen minutes after reexpansion of the right lung, we
found bubbly sputum coming out from the right tracheal tube and cloudy shadow in
the right field of his chest X-ray. The occurrence of reexpansion pulmonary edema
(RPE) was considered. Subsequent mechanical ventilation with PEEP and
administration of steroid and diuretic was done as his treatment. His respiratory
state was stabiized in the next two days. As the lung collapse following
spontaneous hemopneumothorax often becomes more severe, we should pay attention
to the occurrence of RPE after expansion of affected side lung. And, if it
occurred, appropriate and prompt treatment as above should be done because of its
high mortality.
PMID- 26437556
TI - [Anesthetic Management of Two Patients with Chilaiditi Syndrome].
AB - Chilaiditi syndrome is assosiated with hepatodiaphragmatic interposition of the
colon and the small intestines. We anesthetized 2 patients with Chilaiditi
syndrome. A 62-year-old woman with interposition of the intestine was scheduled
for right femoral fibrosarcoma resection. She had been medicated for
schizophrenia. Total intravenous anesthesia was induced and maintained. Another
patient an 81-year-old man with interposition of the colon, was scheduled for
transurethral resection of a bladder tumor. He was anesthetized with spinal
anesthesia. In both cases, there was no cardiovascular complication or digestive
disorder during the perioperative period.
PMID- 26437557
TI - [Usefullness of Beta-blocker for Hemodynamic Changes Induced by Uterotonic Drug
in a Patient with Hypertrophic Obstructive Cardiomyopathy Undergoing Elective
Cesarean Section].
AB - Combined spinal-epidural anesthesia (CSEA) was given to a 27-year-old woman with
hypertrophic obstructive cardiomyopathy (HOCM) for a selective cesarean section.
After the injection of uterotonic drug via uterine muscle and a vein after
delivery, the patient developed dyspnea, tachycardia, ST-change on
elecrocardiogram and hypotension. It is important in HOCM patients to control
heart rate and left ventricular contractile force. We started to infuse beta
blocker (landiolol, 10 MUg x kg(-1) x min(-1)) and improved these symptoms of the
patient. This case demonstrates that CSEA is safe for HOCM patients and beta
blocker is effective to improve hemodynamic changes induced by uterotonic drug in
these patients.
PMID- 26437558
TI - [A Case Report of the Postoperative Epidural Hematoma the Cause of Which Was
Thought to Be the Spinal Abnormality].
AB - Although an 84-year-old patient did not have any coagulopathy and there was no
vascular injury at the time of epidural puncture, epidural hematoma developed
late in onset Ossification of the posterior longitudinal ligament of the spine
was suspected as a potential cause. The vascular hyperplasia in the epidural
space is possible in a case of ossification of the posterior longitudinal
ligament of the spine. A careful observation is necessary after the epidural
catheter insertion in a patient with ossification of the posterior longitudinal
ligament.
PMID- 26437559
TI - [Persistent Bilateral Vocal Cord Paralysis after General Anesthesia in a Patient
with Multiple System Atrophy: A Case Report].
AB - We report a case of persistent bilateral vocal cord paralysis which developed
after spine surgery under general anesthesia in a patient with multiple system
atrophy. A 64-year-old woman was scheduled to receive spinal fusion surgery for
kyphoscoliosis. She did not have apparent symptoms of vocal cord paralysis such
as hoarseness before surgery. The surgery was performed smoothly under general
anesthesia with endotracheal intubation. However, immediately after extubation,
the patient developed severe upper airway obstruction and was re-intubated.
Fiberoptic laryngoscopy revealed bilateral vocal cord abductor paralysis. Vocal
cord paralysis did not improve and she received tracheotomy on the 12th day after
surgery. She also showed symptoms of autonomic nervous system dysfunction and
cerebellar ataxia, and was diagnosed as multiple system atrophy on postoperative
day 64. We discuss differential diagnosis of persistent vocal cord paralysis
after general anesthesia, and anesthetic management of a patient with multiple
system atrophy.
PMID- 26437560
TI - [Cytoreductive Surgery Performed Twice for Pseudomyxoma Peritonei with Pleural
Extension of Mucinous Tumor].
AB - Pseudomyxoma peritonei (PMP) is a condition characterized by production of a
large amount of mucopolysaccharides by neoplastic epithelium, with intraabdominal
cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
known to be viable treatment options. Pleural extension from an PMP is unusual
and thought to be related to diaphragmatic perforation during surgery or
transdiaphragmatic spreading of the disease through the lymphatic lacunae. Here,
we report a patient with PMP with pleural extension of a mucinous tumor for whom
CRS was performed twice. A 57-year-old female with PMP infiltrating the right
chest cavity was scheduled for two separate CRS and hyperthermic chemotherapy
procedures, because of the highly invasive characteristics of the surgery. For
the first operation, we performed intra-abdominal surgery under general
anesthesia combined with epidural anesthesia. To assess fluid and blood
transfusion responsiveness, and reactions to vasoactive medication, we utilized
an arterial pressure-based cardiac output monitor and central venous oximetry
catheter. The second operation was performed 5 months later under general
anesthesia with differential lung ventilation combined with epidural anesthesia.
The operation and anesthesia for both surgical procedures were uneventful.
PMID- 26437561
TI - [A Case of Suspected Delayed Postoperative Malignant Hyperthermia].
AB - Malignant hyperthermia occurred 10 hours after surgery in a 72-year-old man who
had received emergency laparoscopic cholecystectomy for severe acute
cholecystitis with cholelethiasis. He had a high fever (39.4 degrees C) with
liver damage before surgery. Anesthesia was induced with propofol and fentanyl
and maintained with sevoflurane and epidural block using ropivacaine. Rocuronium
was used as a muscle relaxant During surgery, body temperature decreased by
cooling the body surface, but tachycardia continued. Ten hours after surgery,
body temperature increased to the maximum of 40.6 degrees C and he went into
shock. Then another 10 hours later, he developed cardiac arrest He recovered, but
22 hours later, second cardiac arrest occurred. After his second recovery,
dantrolene was administered and body temperature decreased. He had hypoxic brain
damage, but was dischanged from the hospital after tracheostomy on the 150th
hospital day. From his clinical course, especially decrease in body temperature
by dantrolene, he was suspected to have developed malignant hyperthermia. We
should consider malignant hyperthermia when patient had a severe high fever
postoperatively.
PMID- 26437562
TI - [Ultrasound-guided Sciatic Nerve Block (Pulsed Radiofrequency) for Intractable
Cancer Pain Caused by Sacral Bone Metastasis].
AB - We report a case of successful pulsed radiofrequency stimulation of the sciatic
nerve for intractable cancer pain caused by sacral bone metastasis of non-small
cell lung cancer. A 57-year-old man who suffered from intractable left femoral
pain was diagnosed with cancer metastasis to the sacral bone and lumbar spine.
Oral oxycodone relieved the pain at rest but he could not walk or remain sitting
due to the pain during exercise. Oxycodone rescue or increase did not relieve the
pain, but induced drowsiness. Given that sciatic nerve block with mepivacaine was
effective, we performed pulsed radiofrequency with ultrasound guidance twice.
Pulsed radiofrequency relieved the left femoral pain and he could sit for hours
and walk uneventfully. Our finding suggest that ultrasound-guided pulsed
radiofrequency of the sciatic nerve effectively relieves intractable left femoral
pain caused by sacral bone metastasis.
PMID- 26437563
TI - [Successful Anesthetic Management of a Patient with Critical Bleeding during
Hepatectomy Using Recombinant Activated Factor VII and Intraoperative Blood
Salvage].
AB - A 58-year-old 79 kg male with metastatic liver cancer was scheduled for
hepatectomy. Preoperative examination did not reveal any hemostatic
abnormalities. Nine hours into the surgery, a vascular clip attached to the
middle hepatic vein was disconnected and rapid bleeding followed. Unscheduled
intraoperative cell salvage was employed. Despite surgical hemostasis as well as
transfusion with fresh frozen plasma and platelets, significant oozing persisted
for 10 hours, and cumulative blood loss amounted to 30,000 ml. Therefore, we
administered fibrinogen products and recombinant activated factor VLL (rFVIIa,
NovoSeven), a potent hemostatic initiator used in treating congenital factor VII
deficient patients. After injecting 5 mg of rFVIIa, the bleeding was controlled
almost immediately, and the surgery was completed within an hour. Although
postoperative computed tomography detected subclinical but extensive thrombosis
in the middle hepatic vein, the inferior vena cava, and the deep femoral veins,
the thrombus spontaneously dissolved within seven months postoperatively. There
was no evidence of metastatic disease 24 months postoperatively. Off-label use of
rFVIIa and intraoperatively salvaged autologous blood transfusions are life
saving procedures for cancer patients who have massive bleeding during surgery,
although we cannot completely exclude the possibility of serious postoperative
thrombotic events and/or hematogenous cancer dissemination.
PMID- 26437564
TI - [A New Teaching Model for Practicing Ultrasound-guided Regional Anesthesia
Techniques].
AB - We developed a simulator using "slime" composed of polyvinyl alcohol (PVA) and
borax to evaluate this new ultrasound-guided nerve block training model.
Seventeen subjects used the training model in the present study. They had no
previous experience in performing ultrasound-guided nerve block. A plastic case
measuring 25 x 18 x 12 cm was filled with 8 cm of slime. Three pieces of gauze
were placed between the slime layers at 2 cm intervals. An in-plane approach was
used to visualize the needle for the nerve block, and the amount of time required
to stop the needle on the second gauze was measured 5 times for each subject.
Significant differences were observed between the times for the first experiment
and those for the third experiment to the fifth experiment In the fourth and
fifth experiments, all subjects visualized the nerve block needle clearly above
the target layer and were able to stop the needle at the target layer. The
present simulation using our proposed ultrasound-guided nerve block training
model was useful in terms of the amount of time required to perform the procedure
and as well as in terms of its safety.
PMID- 26437565
TI - [Several Issues before and after the Recognition of "Anesthesiology" as
"Specially Approved Specialty"].
PMID- 26437566
TI - Does Mode of Contact with Different Types of Social Relationships Predict
Depression in Older Adults? Evidence from a Nationally Representative Survey.
AB - OBJECTIVES: To determine associations between use of three different modes of
social contact (in person, telephone, written or e-mail), contact with different
types of people, and risk of depressive symptoms in a nationally representative,
longitudinal sample of older adults. DESIGN: Population-based observational
cohort. SETTING: Urban and suburban communities throughout the contiguous United
States. PARTICIPANTS: Individuals aged 50 and older who participated in the
Health and Retirement Survey between 2004 and 2010 (N = 11,065). MEASUREMENTS:
Frequency of participant use of the three modes of social contact with children,
other family members, and friends at baseline were used to predict depressive
symptoms (measured using the eight-item Center for Epidemiologic Studies
Depression Scale) 2 years later using multivariable logistic regression models.
RESULTS: Probability of having depressive symptoms steadily increased as
frequency of in-person-but not telephone or written or e-mail contact-decreased.
After controlling for demographic, clinical, and social variables, individuals
with in-person social contact every few months or less with children, other
family, and friends had a significantly higher probability of clinically
significant depressive symptoms 2 years later (11.5%) than those having in-person
contact once or twice per month (8.1%; P < .001) or once or twice per week (7.3%;
P < .001). Older age, interpersonal conflict, and depression at baseline
moderated some of the effects of social contact on depressive symptoms.
CONCLUSION: Frequency of in-person social contact with friends and family
independently predicts risk of subsequent depression in older adults. Clinicians
should consider encouraging face-to-face social interactions as a preventive
strategy for depression.
PMID- 26437567
TI - Comprehensive treatments for social cognitive deficits in schizophrenia: A
critical review and effect-size analysis of controlled studies.
AB - Recent advances in psychosocial treatments for schizophrenia have targeted social
cognitive deficits. A critical literature review and effect-size (ES) analysis
was conducted to investigate the efficacy of comprehensive programs of social
cognitive training in schizophrenia. Results revealed 16 controlled studies
consisting of seven models of comprehensive treatment with only three of these
treatment models investigated in more than one study. The effects of social
cognitive training were reported in 11/15 studies that included facial affect
recognition skills (ES=.84) and 10/13 studies that included theory-of-mind
(ES=.70) as outcomes. Less than half (4/9) of studies that measured attributional
style as an outcome reported effects of treatment, but effect sizes across
studies were significant (ESs=.30-.52). The effect sizes for symptoms were
modest, but, with the exception of positive symptoms, significant (ESs=.32-.40).
The majority of trials were randomized (13/16), selected active control
conditions (11/16) and included at least 30 participants (12/16). Concerns for
this area of research include the absence of blinded outcome raters in more than
50% of trials and low rates of utilization of procedures for maintaining
treatment fidelity. These findings provide preliminary support for the broader
use of comprehensive social cognitive training procedures as a psychosocial
intervention for schizophrenia.
PMID- 26437568
TI - Sargaquinoic Acid Inhibits TNF-alpha-Induced NF-kappaB Signaling, Thereby
Contributing to Decreased Monocyte Adhesion to Human Umbilical Vein Endothelial
Cells (HUVECs).
AB - Sargaquinoic acid (SQA) has been known for its antioxidant and anti-inflammatory
properties. This study investigated the effects of SQA isolated from Sargassum
serratifolium on the inhibition of tumor necrosis factor (TNF)-alpha-induced
monocyte adhesion to human umbilical vein endothelial cells (HUVECs). SQA
decreased the expression of cell adhesion molecules such as intracellular
adhesion molecule-1 and vascular cell adhesion molecule-1 as well as chemotactic
cytokines such as interleukin-8 and monocyte chemoattractant protein-1 in TNF
alpha-treated HUVECs. As a result, SQA prevented monocyte adhesion to TNF-alpha
induced adhesion. SQA also inhibited TNF-alpha-induced nuclear factor kappa B (NF
kappaB) translocation into the nucleus by preventing proteolytic degradation of
inhibitor kappaB-alpha. Overall, SQA protects against TNF-alpha-induced vascular
inflammation through inhibition of the NF-kappaB pathway in HUVECs. These data
suggest that SQA may be used as a therapeutic agent for vascular inflammatory
diseases such as atherosclerosis.
PMID- 26437569
TI - Through-Space 1,4-Palladium Migration and 1,2-Aryl Shift: Direct Access to
Dibenzo[a,c]carbazoles through a Triple C-H Functionalization Cascade.
AB - A palladium-catalyzed expeditious synthesis of dibenzofused carbazoles from
readily available 2-arylindoles and diaryliodonium salts is reported.
Interestingly, after the electrophilic C3 palladation of indole, an unexpected
"through-space" 1,4-palladium migration to the 2-aryl moiety, by remote C-H bond
activation followed by C-H arylation with diaryliodonium salt, and an
unprecedented 1,2-aryl shift take place. Finally, an intramolecular cross
dehydrogenative coupling (CDC) at the C2 position affords dibenzo[a,c]carbazoles
in high yields. Remarkably, the present migratory annulation occurs through three
C-H bond activation one C-C bond cleavage, and the simultaneous construction of
three new C-C bonds in a single operation.
PMID- 26437570
TI - Time-dependent stabilization of the +1 nucleosome is an early step in the
transition to stable cold-induced repression of FLC.
AB - In vernalized Arabidopsis, the extent of FLC repression and promotion of
flowering are correlated with the length of winter (low temperature exposure),
but how plants measure the duration of winter is unknown. Repression of FLC
occurs in two phases: establishment and maintenance. This study investigates the
early events in the transition between establishment and maintenance of
repression. Initial repression was rapid but transient; within 24 h of being
placed at low temperatures FLC transcription was reduced by 40% and repression
was complete after 5 days in the cold. The extent to which repression was
maintained depended on the length of the cold treatment. Occupancy of the +1
nucleosome in FLC chromatin increased in a time-dependent manner over a 4-week
low temperature treatment concomitant with decreased histone acetylation and
increased trimethylation of histone H3 lysine 27 (H3K27me3). Mutant analyses
showed that increased nucleosome occupancy occurred independent of histone
deacetylation and increased H3K27me3, suggesting that it is an early step in the
switch between transient and stable repression. Both altered histone composition
and deacetylation contributed to increased nucleosome occupancy. The time
dependency of the steps required for the switch between transient and stable
repression suggests that the duration of winter is measured by the chromatin
state at FLC. A chromatin-based switch is consistent with finding that each FLC
allele in a cell undergoes this transition independently.
PMID- 26437571
TI - Oxidative status in treatment-naive essential thrombocythemia: a pilot study in a
single center.
AB - Oxidative stress (OS), due to pro-oxidant species [reactive oxygen species (ROS)]
excess not counterbalanced by endogenous antioxidant molecules [e.g., reduced
glutathione (GSH)], is involved in the pathogenesis of human cancers, but few
data are available on essential thrombocythemia (ET). This study aims to
investigate OS in ET off-therapy patients. Thirty ET treatment-naive patients
were compared with 26 age-matched and gender-matched controls. Serum ROS, urinary
8-hydroxydeoxyguanosine, full blood GSH levels, and reduced/oxidized GSH ratio
(GSH/GSSG) were measured. Data were adjusted for gender, age, JAK2 mutational
status, smoking, dyslipidemia, or hypercholesterolemia requiring drug therapy,
antiplatelet therapy, treatment with acetylsalicylic acid, high-sensitive C
reactive protein levels, and absolute monocyte count. ROS and GSH levels were
increased in both patients and controls. Patients showed increased GSSG (p =
0.05), reduced GSH/GSSG ratio (p = 0.08), and similar 8-hydroxydeoxyguanosine
levels when compared with controls. No differences in OS parameters were found
between JAK2-positive and JAK2-negative patients. Confounding factors did not
modify the results. Our study suggests an OS condition in a cohort of treatment
naive ET patients, not associated with JAK2 mutational status or with chronic
inflammation situation. GSH/GSSG ratio, altered in ET patients because of
increased GSSG levels, showed the presence of higher GSH levels in ET than
controls as a possible compensatory mechanism of an excess of pro-oxidant
production. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26437573
TI - Regulatory Mechanism of the Enantioselective Intramolecular Enone [2+2]
Photocycloaddition Reaction Mediated by a Chiral Lewis Acid Catalyst Containing
Heavy Atoms.
AB - The asymmetric catalysis of the intramolecular enone [2+2] photocycloaddition has
been subject of extensive experimental studies, however theoretical insight to
its regulatory mechanism is still sparse. Accurate quantum chemical calculations
at the CASPT2//CASSCF level of theory associated with energy-consistent
relativistic pseudopotentials provide a basis for the first regulation theory
that the enantioselective reaction is predominantly controlled by the presence of
relativistic effects, that is, spin-orbit coupling resulting from heavy atoms in
the chiral Lewis acid catalyst.
PMID- 26437572
TI - MicroRNA-34a Promotes Hepatic Stellate Cell Activation via Targeting ACSL1.
AB - BACKGROUND: The incidence of liver fibrosis remains high due to the lack of
effective therapies. Our previous work found that microRNA (miR)-34a expression
was increased, while acy1-CoA synthetase long-chain family member1 (ACSL1) was
decreased, in a dimethylnitrosamine (DNS)-induced hepatic fibrosis rat model. We
hypothesized that miR-34a may play a role in the process of hepatic fibrosis by
targeting ACSL1. MATERIAL AND METHODS: From days 2 to 14, cultured primary
hepatic stellate cells (HSCs) underwent cell morphology, immunocytochemical
staining, and quantitative reverse transcription PCR (RT-qPCR) for alpha smooth
muscle actin (a-SMA), desmin, rno-miR-34a, and ACSL1 expression. Wild-type and
mutant luciferase reporter plasmids were constructed according to the predicted
miR-34a binding site on the 3'-untranslated region (UTR) of the ACSL1 mRNA and
then transfected into HEK293 cells. rno-miR-34a was silenced in HSCs to confirm
that rno-miR-34a negatively regulates ACSL1 expression. mRNA and protein
expression of alpha-SMA, type I collagen, and desmin were assayed in miR-34a
silenced HSCs. RESULTS: HSCs were deemed quiescent during the first 3 days and
activated after 10 days. rno-miR-34a expression increased, and ACSL1 expression
decreased, from day 2 to 7 to 14. rno-miR-34a was shown to specifically bind to
the 3'-UTR of ACSL1. miR-34a-silenced HSCs showed higher ACSL1and lower alpha
SMA, type I collagen, and desmin expression than that of matching negative
controls and non-transfected cells. CONCLUSIONS: miR-34a appears to play an
important role in the process of liver fibrosis by targeting ACSL1 and may show
promise as a therapeutic molecular target for hepatic fibrosis.
PMID- 26437574
TI - Altered EEG resting-state effective connectivity in drug-naive childhood absence
epilepsy.
AB - OBJECTIVE: We investigated interictal EEG activity in patients with childhood
absence seizures with the aim of detecting markers of network defects generating
"idiopathic" hyperexcitability in this form of epilepsy. METHODS: We included 11
drug-naive patients with childhood absence epilepsy (CAE), and 11 age matched
controls (CTRL). We analyzed interictal EEG using partial directed coherence
(PDC), a connectivity estimator in frequency domain based on autoregressive
multivariate (MVAR) modeling giving the advantage of indicating the direction and
strength of the interactions between multiple variables. RESULTS: Our results
revealed the presence of an abnormal cortico-cortical network occurring in the
interictal condition in CAE and involving a large span of frequencies, with
prominence in the alpha band; the most evident finding was a highly significant
increase of out-going connectivity involving frontal and central cortical areas
in CAE patients compared to CTRL subjects. CONCLUSIONS: Our observation indicates
that, in interictal conditions, a distorted network characterizes CAE, and a
hyperconnected network is already detectable under resting conditions in the
delta, theta and alpha bands. SIGNIFICANCE: The increased interictal EEG
connectivity demonstrated here provides support for a persistent abnormal
relationship between the thalamus and a hyperexcitable cortex outside the ictal
phase.
PMID- 26437575
TI - Thermoelectricity in polymer composites due to fluctuation-induced tunneling.
AB - Transport in heavily-doped polymer composites, characterized by localized charge
regions, is examined in light of the recent interest in polymers for
thermoelectric applications. The developed fundamental transport theory describes
carrier tunneling between charged localizations by taking into account thermally
induced fluctuations of the applied potential. A range of characteristic
behaviors corresponding to experimental data are described. Deviations from the
Wiedemann-Franz law are also identified. This novel theory enables the
determination of factors dominating the transport in polymers and a comparison to
tunneling without thermal fluctuations is also provided. The obtained asymptotic
expressions for the conductivity, Seebeck coefficient, and carrier thermal
conductivity are particularly useful for elucidating possible routes for
thermoelectric transport control and optimization.
PMID- 26437576
TI - Role of postoperative radiation therapy (PORT) in pT1-T2 N0 deep tongue cancers.
AB - OBJECTIVE: Carcinoma of tongue is associated with a high risk of occult
metastasis and mortality despite early-stage detection and therapy; the critical
tumor thickness at which this risk increases has been demonstrated as 4 mm or
greater. There are no sufficient data in the published literature to evaluate the
role of postoperative radiation therapy (PORT) in the treatment of pT1-T2 N0 oral
tongue cancers with depth of invasion 4 mm or greater. STUDY DESIGN: Historical
cohorts of patients with primary pT1-T2 N0 oral tongue cancer of depth of
invasion 4 mm or greater treated surgically from January 2010 to December 2012
were included in the study, and negative margins on initial resection were
filtered. Locoregional recurrence and death were analyzed among the patients who
received PORT and those who did not. RESULTS: A total of 103 patients fulfilled
the above-mentioned criteria, with 62 patients receiving PORT and 41 patients not
receiving PORT; median period of follow-up was 41.3 months. Logistic and Cox
regression models showed no significant difference in locoregional recurrences (P
= .078) and survival (P = .339) between patients who received PORT and those who
did not receive PORT. CONCLUSIONS: PORT did not influence survival of patients
with stage I and stage II deep tongue cancers, with 4 mm or greater tumor
invasion depth.
PMID- 26437577
TI - Chronic Contusion Spinal Cord Injury Impairs Ejaculatory Reflexes in Male Rats:
Partial Recovery by Systemic Infusions of Dopamine D3 Receptor Agonist 7OHDPAT.
AB - Chronic spinal cord injury (SCI) causes major disruption of ejaculatory function
in men. Ejaculation is a reflex and the spinal generator for ejaculatory reflexes
in the rat has been located in the lumbosacral spinal cord. The effects of SCI on
the rat spinal ejaculation generator and ejaculatory reflexes remain
understudied. The first goal of the current study was to establish the effects of
chronic SCI on the function of the spinal ejaculation generator. Male rats
received a contusion injury of the spinal cord at spinal level T6-T7. Ejaculatory
reflexes elicited by electrical stimulation of the dorsal penile nerve (DPN) were
evaluated in injured and control rats at 4-6 weeks following SCI. SCI males
demonstrated significant reductions in bursting of the bulbocavernosus muscle
(BCM), an indicator for expulsion phase of ejaculation, and in seminal vesicle
pressure (SVP) increases, an indicator for the emission phase of ejaculation,
following DPN stimulation. Thus, contusion SCI resulted in long-term impairment
of ejaculatory reflexes. The D3 agonist 7-hydroxy-2-(di-N-propylamino) tetralin
(7OHDPAT) facilitates ejaculation in spinal cord intact rats, thus the second
goal of the current study was to test whether subcutaneous infusions of 7OHDPAT
can facilitate ejaculatory reflexes in rats with chronic SCI. Male rats received
a contusion injury at T6-T7 and effects of systemic administration of 7OHDPAT (1
mg/kg) were tested 4-5 weeks following injury. Results showed that 7OHDPAT
administration facilitated ejaculatory reflexes in SCI males with or without DPN
stimulation, provided that supraspinal inputs to the lumbar cord were severed by
transection just prior to evaluating the reflex. Thus, 7OHDPAT administration in
SCI males was able to overcome the detrimental effects of SCI on ejaculatory
reflexes.
PMID- 26437578
TI - The 127th Regional Meeting (Kinki Area).
PMID- 26437579
TI - The 132th Regional Meeting (Kanto Area).
PMID- 26437580
TI - A combined omics approach to evaluate the effects of dietary curcumin on colon
inflammation in the Mdr1a(-/-) mouse model of inflammatory bowel disease.
AB - The aim of this study was to provide insight into how curcumin reduces colon
inflammation in the Mdr1a(-/-) mouse model of human inflammatory bowel disease
using a combined transcriptomics and proteomics approach. Mdr1a(-/-) and FVB
control mice were randomly assigned to an AIN-76A (control) diet or AIN-76A+0.2%
curcumin. At 21 or 24weeks of age, colonic histological injury score (HIS) was
determined, colon mRNA transcript levels were assessed using microarrays and
colon protein expression was measured using 2D gel electrophoresis and LCMS
protein identification. Colonic HIS of Mdr1a(-/-) mice fed the AIN-76A diet was
higher (P<.001) than FVB mice fed the same diet; the curcumin-supplemented diet
reduced colonic HIS (P<.05) in Mdr1a(-/-) mice. Microarray and proteomics
analyses combined with new data analysis tools, such as the Ingenuity Pathways
Analysis regulator effects analysis, showed that curcumin's antiinflammatory
activity in Mdr1a(-/-) mouse colon may be mediated by activation of alpha
catenin, which has not previously been reported. We also show evidence to support
curcumin's action via multiple molecular pathways including reduced immune
response, increased xenobiotic metabolism, resolution of inflammation through
decreased neutrophil migration and increased barrier remodeling. Key
transcription factors and other regulatory molecules (ERK, FN1, TNFSF12 and PI3K
complex) activated in inflammation were down-regulated by dietary intervention
with curcumin.
PMID- 26437582
TI - Antimicrobial activity of iron oxide nanoparticle upon modulation of nanoparticle
bacteria interface.
AB - Investigating the interaction patterns at nano-bio interface is a key challenge
for safe use of nanoparticles (NPs) to any biological system. The study intends
to explore the role of interaction pattern at the iron oxide nanoparticle (IONP)
bacteria interface affecting antimicrobial propensity of IONP. To this end, IONP
with magnetite like atomic arrangement and negative surface potential (n-IONP)
was synthesized by co-precipitation method. Positively charged chitosan molecule
coating was used to reverse the surface potential of n-IONP, i.e. positive
surface potential IONP (p-IONP). The comparative data from fourier transform
infrared spectroscope, XRD, and zeta potential analyzer indicated the successful
coating of IONP surface with chitosan molecule. Additionally, the nanocrystals
obtained were found to have spherical size with 10-20 nm diameter. The BacLight
fluorescence assay, bacterial growth kinetic and colony forming unit studies
indicated that n-IONP (<50 MUM) has insignificant antimicrobial activity against
Bacillus subtilis and Escherichia coli. However, coating with chitosan molecule
resulted significant increase in antimicrobial propensity of IONP. Additionally,
the assay to study reactive oxygen species (ROS) indicated relatively higher ROS
production upon p-IONP treatment of the bacteria. The data, altogether, indicated
that the chitosan coating of IONP result in interface that enhances ROS
production, hence the antimicrobial activity.
PMID- 26437581
TI - Innervation and neuromuscular control in ageing skeletal muscle.
AB - Changes in the neuromuscular system affecting the ageing motor unit manifest
structurally as a reduction in motor unit number secondary to motor neuron loss;
fibre type grouping due to repeating cycles of denervation-reinnervation; and
instability of the neuromuscular junction that may be due to either or both of a
gradual perturbation in postsynaptic signalling mechanisms necessary for
maintenance of the endplate acetylcholine receptor clusters or a sudden process
involving motor neuron death or traumatic injury to the muscle fibre.
Functionally, these changes manifest as a reduction in strength and coordination
that precedes a loss in muscle mass and contributes to impairments in fatigue.
Regular muscle activation in postural muscles or through habitual physical
activity can attenuate some of these structural and functional changes up to a
point along the ageing continuum. On the other hand, regular muscle activation in
advanced age (>75 years) loses its efficacy, and at least in rodents may
exacerbate age-related motor neuron death. Transgenic mouse studies aimed at
identifying potential mechanisms of motor unit disruptions in ageing muscle are
not conclusive due to many different mechanisms converging on similar motor unit
alterations, many of which phenocopy ageing muscle. Longitudinal studies of
ageing models and humans will help clarify the cause and effect relationships and
thus, identify relevant therapeutic targets to better preserve muscle function
across the lifespan.
PMID- 26437583
TI - Photopolymer Electrolytes for Sustainable, Upscalable, Safe, and Ambient
Temperature Sodium-Ion Secondary Batteries.
AB - The first example of a photopolymerized electrolyte for a sodium-ion battery is
proposed herein. By means of a preparation process free of solvents, catalysts,
purification steps, and separation steps, it is possible to obtain a three
dimensional polymeric network capable of efficient sodium-ion transport. The
thermal properties of the resulting solid electrolyte separator, characterized by
means of thermogravimetric and calorimetric techniques, are excellent for use in
sustainable energy systems conceived for safe large-scale grid storage. The
photopolymerized electrolyte shows a wide electrochemical stability window up to
4.8 V versus Na/Na(+) along with the highest ionic conductivity (5.1 mS cm(-1) at
20 degrees C) obtained in the field of Na-ion polymer batteries so far and
stable long-term constant-current charge/discharge cycling. Moreover, the
polymeric networks are also demonstrated for the in situ fabrication of
electrode/electrolyte composites with excellent interfacial properties, which are
ideal for all-solid-state, safe, and easily upscalable device assembly.
PMID- 26437584
TI - Ubiquitin-Dependent And Independent Signals In Selective Autophagy.
AB - Selective autophagy regulates the abundance of specific cellular components via a
specialized arsenal of factors, termed autophagy receptors, that target protein
complexes, aggregates, and whole organelles into lysosomes. Autophagy receptors
bind to LC3/GABARAP proteins on phagophore and autophagosome membranes, and
recognize signals on cargoes to deliver them to autophagy. Ubiquitin (Ub), a well
known signal for the degradation of polypeptides in the proteasome, also plays an
important role in the recognition of cargoes destined for selective autophagy. In
addition, a variety of cargoes are committed to selective autophagy pathways by
Ub-independent mechanisms employing protein-protein interaction motifs, Ub-like
modifiers, and sugar- or lipid-based signals. In this article we summarize Ub
dependent and independent selective autophagy pathways, and discuss regulatory
mechanisms and challenges for future studies.
PMID- 26437585
TI - Ligand-Independent Mechanisms of Notch Activity.
AB - Interaction between the Notch receptor and Delta-Serrate-Lag2 (DSL) ligands is
generally deemed to be the starting point of the Notch signaling cascade, after
which, Notch is cleaved and the intracellular domain acts as a transcriptional
coactivator. By contrast, Notch protein can become activated independent of
ligand stimulus through recently identified endosomal trafficking routes as well
as through aberrant regulation of Notch components during Notch trafficking,
ubiquitination, and degradation. In this review, we summarize genes implicated in
ligand-independent Notch activity and remark on the mechanisms by which this
process could occur.
PMID- 26437586
TI - Repair Pathway Choices and Consequences at the Double-Strand Break.
AB - DNA double-strand breaks (DSBs) are cytotoxic lesions that threaten genomic
integrity. Failure to repair a DSB has deleterious consequences, including
genomic instability and cell death. Indeed, misrepair of DSBs can lead to
inappropriate end-joining events, which commonly underlie oncogenic
transformation due to chromosomal translocations. Typically, cells employ two
main mechanisms to repair DSBs: homologous recombination (HR) and classical
nonhomologous end joining (C-NHEJ). In addition, alternative error-prone DSB
repair pathways, namely alternative end joining (alt-EJ) and single-strand
annealing (SSA), have been recently shown to operate in many different conditions
and to contribute to genome rearrangements and oncogenic transformation. Here, we
review the mechanisms regulating DSB repair pathway choice, together with the
potential interconnections between HR and the annealing-dependent error-prone DSB
repair pathways.
PMID- 26437587
TI - Types or States? Cellular Dynamics and Regenerative Potential.
AB - Many of our organs can maintain and repair themselves during homeostasis and
injury, as a result of the action of tissue-specific, multipotent stem cells.
However, recent evidence from mammalian systems suggests that injury stimulates
dramatic plasticity, or transient changes in cell potential, in both stem cells
and more differentiated cells. Planarian flatworms possess abundant stem cells,
making them an exceptional model for understanding the cellular behavior
underlying homeostasis and regeneration. Recent discoveries of cell lineages and
regeneration-specific events provide an initial framework for unraveling the
complex cellular contributions to regeneration. In this review, we discuss the
concept of cellular plasticity in the context of planarian regeneration, and
consider the possibility that pluripotency may be a transient, probabilistic
state exhibited by stem cells.
PMID- 26437588
TI - The Functions of MicroRNAs: mRNA Decay and Translational Repression.
AB - MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs, which regulate
complementary mRNAs by inducing translational repression and mRNA decay. Although
this dual repression system seems to operate in both animals and plants, genetic
and biochemical studies suggest that the mechanism underlying the miRNA-mediated
silencing is different in the two kingdoms. Here, we review the recent progress
in our understanding of how miRNAs mediate translational repression and mRNA
decay, and discuss the contributions of the two silencing modes to the overall
silencing effect in both kingdoms.
PMID- 26437590
TI - The Material Basis of Life.
AB - The manner by which the organization and behaviors of cells arise from the
activities of their constituent molecules remains poorly understood. Approaches
from the physical sciences for studying collective properties may help with this
difficult problem, but they must be adapted to account for the specific
attributes of biological molecules.
PMID- 26437589
TI - Epithelial-Mesenchymal Plasticity: A Central Regulator of Cancer Progression.
AB - The epithelial-mesenchymal transition (EMT) program has emerged as a central
driver of tumor malignancy. Moreover, the recently uncovered link between passage
through an EMT and acquisition of stem-like properties indicates that activation
of the EMT programs serves as a major mechanism for generating cancer stem cells
(CSCs); that is, a subpopulation of cancer cells that are responsible for
initiating and propagating the disease. In this review, we summarize the evidence
supporting the widespread involvement of the EMT program in tumor pathogenesis
and attempt to rationalize the connection between the EMT program and acquisition
of stem cell traits. We propose that epithelial-mesenchymal plasticity is likely
controlled by multiple varients of the core EMT program, and foresee the need to
resolve the various programs and the molecular mechanisms that underlie them.
PMID- 26437592
TI - Beyond the Linear Genome: Paired-End Sequencing as a Biophysical Tool.
AB - Paired-end sequencing has enabled a variety of new methods for high-throughput
interrogation of both genome structure and chromatin architecture. Here, we
discuss how the paired-end paradigm can be used to interpret sequencing data as
biophysical measurements of in vivo chromatin structure that report on single
molecules in single cells.
PMID- 26437591
TI - Border Safety: Quality Control at the Nuclear Envelope.
AB - The unique biochemical identity of the nuclear envelope confers its capacity to
establish a barrier that protects the nuclear compartment and directly
contributes to nuclear function. Recent work uncovered quality control mechanisms
employing the endosomal sorting complexes required for transport (ESCRT)
machinery and a new arm of endoplasmic reticulum-associated protein degradation
(ERAD) to counteract the unfolding, damage, or misassembly of nuclear envelope
proteins and ensure the integrity of the nuclear envelope membranes. Moreover,
cells have the capacity to recognize and triage defective nuclear pore complexes
to prevent their inheritance and preserve the longevity of progeny. These
mechanisms serve to highlight the diverse strategies used by cells to maintain
nuclear compartmentalization; we suggest they mitigate the progression and
severity of diseases associated with nuclear envelope malfunction such as the
laminopathies.
PMID- 26437593
TI - After the Greeting: Realizing the Potential of Physical Models in Cell Biology.
AB - Biophysics is increasingly taking center stage in cell biology as the tools for
precise quantifications of cellular behaviors expand. Interdisciplinary
approaches, combining quantitative physical modeling with cell biology, are of
growing interest to journal editors, funding agencies, and hiring committees.
However, despite an ever-increasing emphasis on the importance of
interdisciplinary research, the student trained in biology may still be at a loss
as to what it actually means. I discuss here some considerations on how to
achieve meaningful and high-quality interdisciplinary work.
PMID- 26437594
TI - An Apoptotic 'Eat Me' Signal: Phosphatidylserine Exposure.
AB - Apoptosis and the clearance of apoptotic cells are essential processes in animal
development and homeostasis. For apoptotic cells to be cleared, they must display
an 'eat me' signal, most likely phosphatidylserine (PtdSer) exposure, which
prompts phagocytes to engulf the cells. PtdSer, which is recognized by several
different systems, is normally confined to the cytoplasmic leaflet of the plasma
membrane by a 'flippase'; apoptosis activates a 'scramblase' that quickly exposes
PtdSer on the cell surface. The molecules that flip and scramble phospholipids at
the plasma membrane have recently been identified. Here we discuss recent
findings regarding the molecular mechanisms of apoptotic PtdSer exposure and the
clearance of apoptotic cells.
PMID- 26437595
TI - Nuclear Reprogramming by Defined Factors: Quantity Versus Quality.
AB - The generation of induced pluripotent stem cells (iPSCs) and directly converted
cells holds great promise in regenerative medicine. However, after in-depth
studies of the murine system, we know that the current methodologies to produce
these cells are not ideal and mostly yield cells of poor quality that might hold
a risk in therapeutic applications. In this review we address the duality found
in the literature regarding the use of 'quality' as a criterion for the clinic.
We discuss the elements that influence reprogramming quality, and provide
evidence that safety and functionality are directly linked to cell quality.
Finally, because most of the available data come from murine systems, we
speculate about what aspects can be applied to human cells.
PMID- 26437596
TI - How Cells Measure Length on Subcellular Scales.
AB - Cells are not just amorphous bags of enzymes, but precise and complex machines.
With any machine, it is important that the parts be of the right size, yet our
understanding of the mechanisms that control size of cellular structures remains
at a rudimentary level in most cases. One problem with studying size control is
that many cellular organelles have complex 3D structures that make their size
hard to measure. Here we focus on linear structures within cells, for which the
problem of size control reduces to the problem of length control. We compare and
contrast potential mechanisms for length control to understand how cells solve
simple geometry problems.
PMID- 26437597
TI - Fibroblasts Lead the Way: A Unified View of 3D Cell Motility.
AB - Primary human fibroblasts are remarkably adaptable, able to migrate in differing
types of physiological 3D tissue and on rigid 2D tissue culture surfaces. The
crawling behavior of these and other vertebrate cells has been studied
intensively, which has helped generate the concept of the cell motility cycle as
a comprehensive model of 2D cell migration. However, this model fails to explain
how cells force their large nuclei through the confines of a 3D matrix
environment and why primary fibroblasts can use more than one mechanism to move
in 3D. Recent work shows that the intracellular localization of myosin II
activity is governed by cell-matrix interactions to both force the nucleus
through the extracellular matrix (ECM) and dictate the type of protrusions used
to migrate in 3D.
PMID- 26437598
TI - A Unified Material Description for Light Induced Deformation in Azobenzene
Polymers.
AB - Complex light-matter interactions in azobenzene polymers have limited our
understanding of how photoisomerization induces deformation as a function of the
underlying polymer network and form of the light excitation. A unified modeling
framework is formulated to advance the understanding of surface deformation and
bulk deformation of polymer films that are controlled by linear or circularly
polarized light or vortex beams. It is shown that dipole forces strongly respond
to polarized light in contrast to higher order quadrupole forces that are often
used to describe surface relief grating deformation through a field gradient
constitutive law. The modeling results and comparisons with a broad range of
photomechanical data in the literature suggest that the molecular structure of
the azobenzene monomers dramatically influences the photostrictive behavior. The
results provide important insight for designing azobenzene monomers within a
polymer network to achieve enhanced photo-responsive deformation.
PMID- 26437599
TI - Competition between global warming and an abrupt collapse of the AMOC in Earth's
energy imbalance.
AB - A collapse of the Atlantic Meridional Overturning Circulation (AMOC) leads to
global cooling through fast feedbacks that selectively amplify the response in
the Northern Hemisphere (NH). How such cooling competes with global warming has
long been a topic for speculation, but was never addressed using a climate model.
Here it is shown that global cooling due to a collapsing AMOC obliterates global
warming for a period of 15-20 years. Thereafter, the global mean temperature
trend is reversed and becomes similar to a simulation without an AMOC collapse.
The resulting surface warming hiatus lasts for 40-50 years. Global warming and
AMOC-induced NH cooling are governed by similar feedbacks, giving rise to a
global net radiative imbalance of similar sign, although the former is associated
with surface warming, the latter with cooling. Their footprints in outgoing
longwave and absorbed shortwave radiation are very distinct, making attribution
possible.
PMID- 26437600
TI - Nondestructive Quantification of Local Plasticizer Concentration in PVC by (1)H
NMR Relaxometry.
AB - The properties of plasticized poly(vinyl chloride) (PVC) , one of the most
important polymers today, are strongly dictated by the concentration of
plasticizer. Yet, it has been impossible to quantify this concentration at
different positions inside a PVC product without its destruction because of a
lack of suitable analytical methods. Thus, this paper introduces a simple, fast,
and efficient way to determine truly nondestructively the concentration of
plasticizer in PVC by single-sided nuclear magnetic resonance (NMR). With the
help of correlation curves between the concentration of plasticizer inside
nonaged PVC samples and the corresponding volume-averaged NMR parameters, single
sided NMR allows the quantification of the local concentration of plasticizer in
aged PVC plates at different depths by spatially resolved relaxation
measurements. The presented approach represents a fundamental step toward in situ
characterization of plasticized PVC.
PMID- 26437601
TI - Human rights in maternity care.
PMID- 26437602
TI - Global Phosphoproteomic Analysis of Human Skeletal Muscle Reveals a Network of
Exercise-Regulated Kinases and AMPK Substrates.
AB - Exercise is essential in regulating energy metabolism and whole-body insulin
sensitivity. To explore the exercise signaling network, we undertook a global
analysis of protein phosphorylation in human skeletal muscle biopsies from
untrained healthy males before and after a single high-intensity exercise bout,
revealing 1,004 unique exercise-regulated phosphosites on 562 proteins. These
included substrates of known exercise-regulated kinases (AMPK, PKA, CaMK, MAPK,
mTOR), yet the majority of kinases and substrate phosphosites have not previously
been implicated in exercise signaling. Given the importance of AMPK in exercise
regulated metabolism, we performed a targeted in vitro AMPK screen and employed
machine learning to predict exercise-regulated AMPK substrates. We validated
eight predicted AMPK substrates, including AKAP1, using targeted
phosphoproteomics. Functional characterization revealed an undescribed role for
AMPK-dependent phosphorylation of AKAP1 in mitochondrial respiration. These data
expose the unexplored complexity of acute exercise signaling and provide insights
into the role of AMPK in mitochondrial biochemistry.
PMID- 26437605
TI - Oxygen Sensing by Arterial Chemoreceptors Depends on Mitochondrial Complex I
Signaling.
AB - O2 sensing is essential for mammalian homeostasis. Peripheral chemoreceptors such
as the carotid body (CB) contain cells with O2-sensitive K(+) channels, which are
inhibited by hypoxia to trigger fast adaptive cardiorespiratory reflexes. How
variations of O2 tension (PO2) are detected and the mechanisms whereby these
changes are conveyed to membrane ion channels have remained elusive. We have
studied acute O2 sensing in conditional knockout mice lacking mitochondrial
complex I (MCI) genes. We inactivated Ndufs2, which encodes a protein that
participates in ubiquinone binding. Ndufs2-null mice lose the hyperventilatory
response to hypoxia, although they respond to hypercapnia. Ndufs2-deficient CB
cells have normal functions and ATP content but are insensitive to changes in
PO2. Our data suggest that chemoreceptor cells have a specialized succinate
dependent metabolism that induces an MCI state during hypoxia, characterized by
the production of reactive oxygen species and accumulation of reduced pyridine
nucleotides, which signal neighboring K(+) channels.
PMID- 26437603
TI - Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular
Hypertrophy.
AB - Chronic kidney disease (CKD) is a worldwide public health threat that increases
risk of death due to cardiovascular complications, including left ventricular
hypertrophy (LVH). Novel therapeutic targets are needed to design treatments to
alleviate the cardiovascular burden of CKD. Previously, we demonstrated that
circulating concentrations of fibroblast growth factor (FGF) 23 rise
progressively in CKD and induce LVH through an unknown FGF receptor (FGFR)
dependent mechanism. Here, we report that FGF23 exclusively activates FGFR4 on
cardiac myocytes to stimulate phospholipase Cgamma/calcineurin/nuclear factor of
activated T cell signaling. A specific FGFR4-blocking antibody inhibits FGF23
induced hypertrophy of isolated cardiac myocytes and attenuates LVH in rats with
CKD. Mice lacking FGFR4 do not develop LVH in response to elevated FGF23, whereas
knockin mice carrying an FGFR4 gain-of-function mutation spontaneously develop
LVH. Thus, FGF23 promotes LVH by activating FGFR4, thereby establishing FGFR4 as
a pharmacological target for reducing cardiovascular risk in CKD.
PMID- 26437606
TI - Pregnancy outcome after blastocyst stage transfer comparing to early cleavage
stage embryo transfer.
AB - Blastocyst transfer has been introduced as an alternative for improving the
chance for in vitro fertilizations (IVF) implantation. The present study was to
evaluate pregnancy rates when embryo transfer was performed either on day 2-3
(cleavage stage) or on day 4-5 (blastocyst stage). This randomized clinical trial
included 118 infertile women. All the study subjects underwent controlled ovarian
stimulation using a long protocol and randomized into two groups. BS group (n =
57), the culture was extended to day 5 (blastocyst stage) and in the CS-group (n
= 61), embryo culture was continued to day 3 (cleavage stage). Ongoing
pregnancies, abortion, implantation rate were evaluated. No significant
differences were seen in the pregnancy rate between the two groups (33.3% in the
BS group versus 27.9% in the CS group; p = 0.519). Abortion, implantation rate in
two groups are not significant. Despite the lack of statistical difference
between the two study groups, our data suggest that blastocyst transfer may be
associated with a higher pregnancy and an overall better implantation rates.
However, further studies with larger sample size are mandatory to confirm these
findings.
PMID- 26437607
TI - Optimization of silver nanowire-based transparent electrodes: effects of density,
size and thermal annealing.
AB - Silver nanowire (AgNW) networks are efficient as flexible transparent electrodes,
and are cheaper to fabricate than ITO (Indium Tin Oxide). Hence they are a
serious competitor as an alternative to ITO in many applications such as solar
cells, OLEDs, transparent heaters. Electrical and optical properties of AgNW
networks deposited on glass are investigated in this study and an efficient
method to optimize them is proposed. This paper relates network density, nanowire
dimensions and thermal annealing directly to the physical properties of the
nanowire networksusing original physical models. A fair agreement is found
between experimental data and the proposed models. Moreover thermal stability of
the nanowires is a key issue in thermal optimization of such networks and needs
to be studied. In this work the impact of these four parameters on the networks
physical properties are thoroughly investigated via in situ measurements and
modelling, such a method being also applicable to other metallic nanowire
networks. We demonstrate that this approach enables the optimization of both
optical and electrical properties through modification of the junction resistance
by thermal annealing, and a suitable choice of nanowire dimensions and network
density. This work reports excellent optical and electrical properties of
electrodes fabricated from AgNW networks with a transmittance T = 89.2% (at 550
nm) and a sheet resistance of Rs = 2.9 Omega ?(-1), leading to the highest
reported figure of merit.
PMID- 26437604
TI - Ironing out Ferroportin.
AB - Maintaining physiologic iron concentrations in tissues is critical for metabolism
and host defense. Iron absorption in the duodenum, recycling of iron from
senescent erythrocytes, and iron mobilization from storage in macrophages and
hepatocytes constitute the major iron flows into plasma for distribution to
tissues, predominantly for erythropoiesis. All iron transfer to plasma occurs
through the iron exporter ferroportin. The concentration of functional membrane
associated ferroportin is controlled by its ligand, the iron-regulatory hormone
hepcidin, and fine-tuned by regulatory mechanisms serving iron homeostasis,
oxygen utilization, host defense, and erythropoiesis. Fundamental questions about
the structure and biology of ferroportin remain to be answered.
PMID- 26437608
TI - 2D NMR Trace Analysis by Continuous Hyperpolarization at High Magnetic Field.
AB - Nuclear magnetic resonance is often the technique of choice in chemical analysis
because of its sensitivity to molecular structure, quantitative character, and
straightforward sample preparation. However, determination of trace analytes in
complex mixtures is generally limited by low sensitivity and extensive signal
overlap. Here, we present an approach for continuous hyperpolarization at high
magnetic field that is based on signal amplification by reversible exchange
(SABRE) and can be straightforwardly incorporated in multidimensional NMR
experiments. This method was implemented in a 2D correlation experiment that
allows detection and quantification of analytes at nanomolar concentration in
complex solutions.
PMID- 26437609
TI - Surface toughness of silicon nitride bioceramics: II, Comparison with commercial
oxide materials.
AB - Raman microprobe-assisted indentation, a micromechanics method validated in a
companion paper, was used to compare the surface toughening behaviors of silicon
nitride (Si3N4) and alumina-based bioceramics employed in joint arthroplasty
(i.e., monolithic alumina, Al2O3, and yttria-stabilized zirconia (ZrO2)-toughened
alumina, ZTA). Quantitative assessments of microscopic stress fields both ahead
and behind the tip of Vickers indentation cracks propagated under increasing
indentation loads were systematically made using a Raman microprobe with spatial
resolution on the order of a single micrometer. Concurrently, crack opening
displacement (COD) profiles were monitored on the same microcracks screened by
Raman spectroscopy. The Raman eye clearly visualized different mechanisms
operative in toughening Si3N4 and ZTA bioceramics (i.e., crack-face bridging and
ZrO2 polymorphic transformation, respectively) as compared to the brittle
behavior of monolithic Al2O3. Moreover, emphasis was placed on assessing not only
the effectiveness but also the durability of such toughening effects when the
biomaterials were aged in a hydrothermal environment. A significant degree of
embrittlement at the biomaterial surface was recorded in the transformation
toughened ZTA, with the surface toughness reduced by exposure to the hydrothermal
environment. Conversely, the Si3N4 biomaterial experienced a surface toughness
value independent of hydrothermal attack. Crack-face bridging thus appears to be
a durable surface toughening mechanism for biomaterials in joint arthroplasty.
PMID- 26437610
TI - Transient behavior and relaxation of microcapsules with a cross-linked human
serum albumin membrane.
AB - Capsules consist of droplets enclosed by a membrane with shear resistant
properties especially when fabricated by interfacial cross-linking. In many
applications, the protection and release of the internal medium need to be
strictly controlled. It is possible to tune the membrane mechanical properties by
changing the physico-chemical conditions of the fabrication process, but a good
control of the production requires their characterization, which is a scientific
challenge, since the objects are a few tens of microns in size at most. One
advantageous approach is to resort to microfluidic techniques. We study the
transient response of capsules having a cross-linked human serum albumin (HSA)
membrane, as they flow through a sudden expansion. We determine the
characteristic time scales of the capsule relaxation and compare them to the ones
predicted by a full numerical model of the relaxation of a capsule flowing in a
rectangular channel, for which the membrane is assumed to be purely elastic. We
show that the membrane is viscoelastic and that the relaxation is solely a
function of the ratio of the relaxation time to the convective time.
PMID- 26437611
TI - The Utility of Positron Emission Tomography in Epilepsy.
AB - The role of fludeoxyglucose F 18 positron emission tomography (PET) in the
presurgical evaluation of patients with medically intractable epilepsy continues
to be refined. The purpose of this study was to systematically review the
literature to assess the diagnostic accuracy and utility of PET in this setting.
Thirty-nine studies were identified through MEDLINE and EMBASE databases that met
the inclusion criteria. In adult patients, PET hypometabolism showed a 56 to 90%
agreement with seizure onset localized by intracranial electroencephalogram
(pediatric: 21 to 86%). In temporal lobe epilepsy patients with good surgical
outcome, PET displayed moderate to high sensitivity in localizing the seizure
focus (range: 71 to 89%). The sensitivity increased by 8 to 23% when PET results
were combined with magnetic resonance imaging or electroencephalogram. PET has
been shown to affect patient management by improving the guidance of intracranial
electrodes placement, altering the decision to perform surgery, or excluding
patients from further evaluation.
PMID- 26437612
TI - Toward a personalized calorie prescription.
PMID- 26437613
TI - Chamomile tea improves glycemic indices and antioxidants status in patients with
type 2 diabetes mellitus.
AB - OBJECTIVES: Oxidative stress is a major factor in the pathogenesis of diabetes
complications. The objectives were to investigate the effects of chamomile tea
consumption on glycemic control and antioxidant status in subjects with type 2
diabetes mellitus (T2 DM). METHODS: This single-blind randomized controlled
clinical trial was conducted on 64 subjects with T2 DM (males and females) ages
30 to 60 y. The intervention group (n = 32) consumed chamomile tea (3 g/150 mL
hot water) 3 times per day immediately after meals for 8 wk. The control group (n
= 32) followed a water regimen for same intervention period. Fasting blood
samples, anthropometric measurements, and 3-d, 24-h dietary recalls were
collected at the baseline and at the end of the trial. Data were analyzed by
independent t test, paired t test, and analysis of covariance. RESULTS: Chamomile
tea significantly decreased concentration of glycosylated hemoglobin, serum
insulin levels, homeostatic model assessment for insulin resistance, and serum
malondialdehyde, compared with control group (all P < 0.05). Total antioxidant
capacity, superoxide dismutase, glutathione peroxidase, and catalase activities
were significantly increased by 6.81%, 26.16 %, 36.71 % and 45.06% respectively
in chamomile group compared with these variables in control group at the end of
the intervention (all P < 0.05). CONCLUSIONS: Short term intake of chamomile tea
has beneficial effects on glycemic control and antioxidant status in patients
with T2 DM. A larger sample population and a longer intervention period may be
required to show significant clinical improvements.
PMID- 26437615
TI - Ruthenium-Grafted Vinylhelicenes: Chiroptical Properties and Redox Switching.
AB - The properties of mono- and bis-Ru-vinyl[6]helicene complexes (2 a and 2 b,
respectively), recently synthesized by using molecular engineering of helicenes
based on the grafting of lateral organometallic substituents on the pi-helical
backbone through a vinyl bridge, are presented. These helicene derivatives are
thoroughly characterized, with special attention given to their chiroptical
properties and redox switching activity. The UV/Vis and electronic circular
dichroism (ECD) spectra of P and M enantiopure species, both in the neutral and
oxidized states ([2 a](.+), [2 b](.+), and [2 b](2+)), are analyzed with the aid
of quantum-chemical calculations. The extended pi-conjugation facilitated by the
vinyl moiety, clearly visible in the electronic structures of 2 a,b, introduces
new active bands in the ECD spectra that consequently lead to a significant
increase in optical rotation of Ru-vinylhelicenes compared with the organic
precursors. The vibrational circular dichroism (VCD) spectra were measured and
calculated for both the organic and organometallic species and constitute the
first examples of VCD for metal-based helicene derivatives. Finally, the redox
triggered chiroptical switching activity of 2 a,b is examined in detail by using
ECD spectroscopy. The modifications of the ECD spectra in the UV/Vis and NIR
region are well reproduced and rationalized by calculations.
PMID- 26437614
TI - Respiratory syncytial virus induces phosphorylation of mTOR at ser2448 in CD8 T
cells from nasal washes of infected infants.
AB - Respiratory syncytial virus (RSV)-specific CD8(+) T cell responses do not protect
against reinfection. Activation of mammalian target of rapamycin (mTOR) impairs
memory CD8(+) T cell differentiation. Our hypothesis was that RSV inhibits the
formation of CD8(+) T cells memory responses through mTOR activation. To explore
this, human and mouse T cells were used. RSV induced mTOR phosphorylation at
Ser2448 in CD8 T cells. mTOR activation by RSV was completely inhibited using
rapamycin. RSV-infected children presented higher mTOR gene expression on nasal
washes comparing to children infected with metapneumovirus and rhinovirus. In
addition, RSV-infected infants presented a higher frequency of CD8(+)
pmTORser2448(+) T cells in nasal washes compared to RSV-negative infants.
Rapamycin treatment increased the frequency of mouse CD8 RSV-M282-90 pentamer
positive T cells and the frequency of RSV-specific memory T cells precursors.
These data demonstrate that RSV is activating mTOR directly in CD8 T cells,
indicating a role for mTOR during the course of RSV infection.
PMID- 26437617
TI - Obesity: Beige adipocytes-will they beat obesity?
PMID- 26437618
TI - Bone: Irisin boosts bone mass.
PMID- 26437622
TI - Decade in review-thyroid disease: The endocrinology of thyroid disease from 2005
to 2015.
PMID- 26437621
TI - Short and tall stature: a new paradigm emerges.
AB - In the past, the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis
was often considered to be the main system that regulated childhood growth and,
therefore, determined short stature and tall stature. However, findings have now
revealed that the GH-IGF-1 axis is just one of many regulatory systems that
control chondrogenesis in the growth plate, which is the biological process that
drives height gain. Consequently, normal growth in children depends not only on
GH and IGF-1 but also on multiple hormones, paracrine factors, extracellular
matrix molecules and intracellular proteins that regulate the activity of growth
plate chondrocytes. Mutations in the genes that encode many of these local
proteins cause short stature or tall stature. Similarly, genome-wide association
studies have revealed that the normal variation in height seems to be largely due
to genes outside the GH-IGF-1 axis that affect growth at the growth plate through
a wide variety of mechanisms. These findings point to a new conceptual framework
for understanding short and tall stature that is centred not on two particular
hormones but rather on the growth plate, which is the structure responsible for
height gain.
PMID- 26437624
TI - Fit the operation to the patient, not the patient to the operation.
PMID- 26437625
TI - Efficacy of gadoxetic acid-enhanced magnetic resonance cholangiography compared
with T2-weighted magnetic resonance cholangiography in patients with liver
cirrhosis.
AB - BACKGROUND: Gadoxetic acid is one of the hepatobiliary-specific agents and so can
be used for contrast-enhanced magnetic resonance cholangiography (CE-MRC). The
aim of our study was to compare the performance of CE-MRC with that of T2
weighted magnetic resonance cholangiography (T2W-MRC), and also to ascertain the
effectiveness of both modalities combined for visualizing anatomic structures of
the biliary tree in patients with liver cirrhosis. METHODS: Fifty-six patients
underwent CE-MRC and T2W-MRC imaging. In the CE-MRC studies, hepatobiliary phase
images were acquired 20 minutes after contrast injection. Two radiologists first
evaluated the T2W-MRC and CE-MRC images separately in random order, and then they
reviewed both images together 8 weeks later. The readers graded the quality of
visualization of each biliary duct and the entire biliary tree (overall rating)
using a five-point scale. Images with a grade of 3 or 4 were considered to
provide sufficient visualization for clinical application, and those with a grade
of 2 or less were considered to provide insufficient visualization. Laboratory
data, Child-Pugh classification, and model for end-stage liver disease score were
also recorded. RESULTS: The overall rating of T2W-MRC was significantly higher
than that of CE-MRC (p < 0.001), although combined T2W/CE-MRC provided better
visualization of biliary segments than T2W-MRC alone (p = 0.025). There were no
significant differences between liver function and the overall rating of CE-MRC.
CONCLUSION: CE-MRC is not superior to conventional T2W-MRC with respect to
biliary visualization in patients with liver cirrhosis. However, a combination of
T2W-MRC and CE-MRC provides significantly better visualization of biliary
structures than T2W-MRC alone.
PMID- 26437623
TI - Hormonal control of T-cell development in health and disease.
AB - The physiology of the thymus, the primary lymphoid organ in which T cells are
generated, is controlled by hormones. Data from animal models indicate that
several peptide and nonpeptide hormones act pleiotropically within the thymus to
modulate the proliferation, differentiation, migration and death by apoptosis of
developing thymocytes. For example, growth hormone and prolactin can enhance
thymocyte proliferation and migration, whereas glucocorticoids lead to the
apoptosis of these developing cells. The thymus undergoes progressive age
dependent atrophy with a loss of cells being generated and exported, therefore,
hormone-based therapies are being developed as an alternative strategy to
rejuvenate the organ, as well as to augment thymocyte proliferation and the
export of mature T cells to peripheral lymphoid organs. Some hormones (such as
growth hormone and progonadoliberin-1) are also being used as therapeutic agents
to treat immunodeficiency disorders associated with thymic atrophy, such as HIV
infection. In this Review, we discuss the accumulating data that shows the thymus
gland is under complex and multifaceted hormonal control that affects the process
of T-cell development in health and disease.
PMID- 26437626
TI - Mycobacterium tuberculosis nucleic acid amplification tests reduce nosocomial
tuberculosis exposure in intensive care units: A nationwide cohort study.
AB - BACKGROUND AND OBJECTIVE: This retrospective national surveillance study
investigated the burden of and risk factors for nosocomial exposure of pulmonary
tuberculosis (TB) in intensive care units. METHODS: Patients admitted to
intensive care units were identified from the National Health Insurance Research
Database. During 2004-2009, there were 1 387 707 intensive care unit admissions
of 900 562 adult patients. Pulmonary tuberculosis association was considered if
the patient was diagnosed with pulmonary tuberculosis during admission or within
3 months after discharge. Nosocomial transmissible period was calculated based on
the length of anti-tuberculosis treatment and negative-pressure isolation during
admission. RESULTS: Pulmonary tuberculosis was associated with 1.20% of all
intensive care unit admissions and 6731 (38.9%) started anti-TB treatment during
admission. For the other 10 583 admissions, the diagnosis was made after
discharge and anti-TB treatment was not prescribed during admission. The
probability paralleled the regional tuberculosis incidence. On average, 2794
pulmonary tuberculosis associated intensive care unit admissions contributed to
42 999-44 062 days of nosocomial exposure per year. The length of nosocomial
transmissible period decreased with the gradual implementation of Mycobacterium
tuberculosis nucleic acid amplification tests in intensive care practice.
Multivariate linear regression analysis revealed that the length of nosocomial
transmissible period was inversely associated with male gender, airway symptoms
prior to admission and performing M. tuberculosis nucleic acid amplification
tests and mycobacterial culture. CONCLUSIONS: Nosocomial tuberculosis exposure is
not uncommon in intensive care units. Performing rapid molecular diagnostic tests
in those suspected of tuberculosis is recommended to reduce the risk of
nosocomial exposure.
PMID- 26437627
TI - Trapping, entrainment and synchronization of semiflexible polymers in narrow,
asymmetric confinements.
AB - The physical properties of polymeric actin facilitate many mechanical processes
within the cell, including cellular deformation and locomotion, whereby the
polymers can be confined to a range of different geometries. As actin polymers
often form entangled solutions in the cell, we have investigated the effect of
confinement on the evolution of entangled semiflexible polymer solutions. Using a
microfluidic platform, we examined the physical dynamics of actin polymers
confined within narrow (2-4 MUm) rectangular channels. Focusing on the
entanglement process of two actin polymers, we found that their prolonged
entrainment leads to synchronized horizontal undulations and decreased
translational diffusion. In the absence of cross-linking molecules or proteins,
the long-range entrainment interactions are predominantly controlled by the
geometric boundaries. We directly measure the deflection length Lambda for an
individual polymer, either solitarily confined within a channel or confined in
the presence of a second filament, enabling the determination of the change in
free energy associated with polymer entanglement. Our results indicate that
geometrical confinement can serve as a solitary variable influencing the physical
dynamics of entangled semiflexible polymers.
PMID- 26437628
TI - Cytomegalovirus antiviral drug resistance: future prospects for prevention,
detection and management.
PMID- 26437629
TI - How to use mechanistic effect models in environmental risk assessment of
pesticides: Case studies and recommendations from the SETAC workshop MODELINK.
AB - Mechanistic effect models (MEMs) are useful tools for ecological risk assessment
of chemicals to complement experimentation. However, currently no recommendations
exist for how to use them in risk assessments. Therefore, the Society of
Environmental Toxicology and Chemistry (SETAC) MODELINK workshop aimed at
providing guidance for when and how to apply MEMs in regulatory risk assessments.
The workshop focused on risk assessment of plant protection products under
Regulation (EC) No 1107/2009 using MEMs at the organism and population levels.
Realistic applications of MEMs were demonstrated in 6 case studies covering
assessments for plants, invertebrates, and vertebrates in aquatic and terrestrial
habitats. From the case studies and their evaluation, 12 recommendations on the
future use of MEMs were formulated, addressing the issues of how to translate
specific protection goals into workable questions, how to select species and
scenarios to be modeled, and where and how to fit MEMs into current and future
risk assessment schemes. The most important recommendations are that protection
goals should be made more quantitative; the species to be modeled must be
vulnerable not only regarding toxic effects but also regarding their life history
and dispersal traits; the models should be as realistic as possible for a
specific risk assessment question, and the level of conservatism required for a
specific risk assessment should be reached by designing appropriately
conservative environmental and exposure scenarios; scenarios should include
different regions of the European Union (EU) and different crops; in the long
run, generic MEMs covering relevant species based on representative scenarios
should be developed, which will require EU-level joint initiatives of all
stakeholders involved. The main conclusion from the MODELINK workshop is that the
considerable effort required for making MEMs an integral part of environmental
risk assessment of pesticides is worthwhile, because it will make risk
assessments not only more ecologically relevant and less uncertain but also more
comprehensive, coherent, and cost effective.
PMID- 26437630
TI - Adverse Events Associated with Fosfomycin Use: Review of the Literature and
Analyses of the FDA Adverse Event Reporting System Database.
AB - INTRODUCTION: The growing problem of antibacterial resistance resulted in an
increased interest in fosfomycin, especially its parenteral formulation. We
reviewed fosfomycin safety profile using the Food and Drug Administration Adverse
Event (AE) Reporting System (FAERS) and published literature. METHODS: We
conducted a FAERS search and disproportionality analysis of all fosfomycin
associated AEs. We also conducted a FAERS search for AEs implicating fosfomycin
as the primary suspect and a search of reports of fosfomycin-associated bone
marrow toxicity. We then review the literature for publications reporting AEs
associated with fosfomycin by conducting PubMed searches. RESULTS: The
disproportionality analysis of all FAERS reports of fosfomycin-associated AEs
produced a higher than expected frequency of agranulocytosis, liver injury,
severe skin reactions, and pseudomembranous colitis. Subsequent search for AEs
where fosfomycin was the primary suspect and the literature review did not
suggest a higher association of fosfomycin with these AEs. The search of bone
marrow toxicity reports did not demonstrate an association between aplastic
anemia and fosfomycin. The literature review selected 23 trials of parenteral
administration of fosfomycin in 1242 patients including 8 comparative and 15 non
comparative trials. For oral fosfomycin, only prospective comparative trials (n =
28) in 2743 patients were included. The most frequent AEs associated with
parenteral fosfomycin included rash, peripheral phlebitis, hypokalemia, and
gastrointestinal disorders. Serious AEs such as aplastic anemia, anaphylaxis, and
liver toxicities were reported infrequently. Gastrointestinal disorders were the
most common AEs associated with oral fosfomycin. CONCLUSION: The identified AEs
were consistent with the safety profile of fosfomycin. No new safety signals
related to either parenteral or oral fosfomycin were identified.
PMID- 26437632
TI - Have Ecosystem Services Been Oversold?
AB - The concept of ecosystem services (ES) neatly encapsulates the ways in which
human society depends upon the existence and functioning of nature, but also
draws power by chiming with dominant neoliberal ideology. Scientific paradigms
such as this have an inherent tendency to stop adherents from recognizing
alternative approaches. It is high time to examine whether the concept is being
oversold with potentially damaging consequences. Many authors have questioned the
monetization of ES, but the origin of the problem lies deeper in
anthropocentrism. By illustration with alternatives, I attempt to show how the ES
paradigm has constrained thought, particularly towards the monetization and
financialization of nature, even when many ecologists and others oppose this
trend.
PMID- 26437631
TI - Identification of a FOXP3(+)CD3(+)CD56(+) population with immunosuppressive
function in cancer tissues of human hepatocellular carcinoma.
AB - The liver resident lymphoid population is featured by the presence of a large
number of CD3(+)CD56(+) cells referred as natural T cells. In human
hepatocellular carcinoma (HCC) patients, the natural T cells were found to be
sharply decreased in tumor (5.871 +/- 3.553%) versus non-tumor (14.02 +/- 6.151%)
tissues. More intriguingly, a substantial fraction of the natural T cells (22.76
+/- 18.61%) assumed FOXP3 expression. These FOXP3-expressing CD3(+)CD56(+) cells
lost the expression of IFN-gamma and perforin, which are critical for the
effector function of natural T cells. On the other hand, they acquired surface
expression of CD25 and CTLA-4 typically found in regulatory T (Treg) cells.
Consistent with the phenotypic conversion, they imposed an inhibitory effect on
anti-CD3-induced proliferation of naive T cells. Further studies demonstrated
that transforming growth factor beta1 (TGF-beta1) could effectively induce FOXP3
expression in CD3(+)CD56(+) cells and the cells were thus endowed with a potent
immunosuppressive capacity. Finally, Kaplan-Meier analysis revealed that the
relative abundance of FOXP3-expressing CD3(+)CD56(+) cells in tumor tissues was
significantly correlated with the survival of HCC patients. In conclusion, the
present study identified a new type of regulatory immune cells whose emergence in
liver cancer tissues may contribute to tumor progression.
PMID- 26437633
TI - Biodiversity and Resilience of Ecosystem Functions.
AB - Accelerating rates of environmental change and the continued loss of global
biodiversity threaten functions and services delivered by ecosystems. Much
ecosystem monitoring and management is focused on the provision of ecosystem
functions and services under current environmental conditions, yet this could
lead to inappropriate management guidance and undervaluation of the importance of
biodiversity. The maintenance of ecosystem functions and services under
substantial predicted future environmental change (i.e., their 'resilience') is
crucial. Here we identify a range of mechanisms underpinning the resilience of
ecosystem functions across three ecological scales. Although potentially less
important in the short term, biodiversity, encompassing variation from within
species to across landscapes, may be crucial for the longer-term resilience of
ecosystem functions and the services that they underpin.
PMID- 26437634
TI - Misconceptions of Fragmentation's Effects on Ecosystem Services: A Response to
Mitchell et al.
PMID- 26437635
TI - Landscape Fragmentation and Ecosystem Services: A Reply to Andrieu et al.
PMID- 26437636
TI - Emerging Technologies to Conserve Biodiversity.
AB - Technologies to identify individual animals, follow their movements, identify and
locate animal and plant species, and assess the status of their habitats remotely
have become better, faster, and cheaper as threats to the survival of species are
increasing. New technologies alone do not save species, and new data create new
problems. For example, improving technologies alone cannot prevent poaching:
solutions require providing appropriate tools to the right people. Habitat loss
is another driver: the challenge here is to connect existing sophisticated remote
sensing with species occurrence data to predict where species remain. Other
challenges include assembling a wider public to crowdsource data, managing the
massive quantities of data generated, and developing solutions to rapidly
emerging threats.
PMID- 26437637
TI - Pre-alcoholic fermentation acidification of red grape must using Lactobacillus
plantarum.
AB - Red grape musts from overripe grapes are characterised by high pH and sugar
concentration. Corrections with organic acids are commonly used to secure the
alcoholic fermentation and improve the organoleptic characteristics of the wine.
In this study we test an alternative biological acidification method using the
ability of Lactobacillus plantarum to produce high concentrations of lactic acid.
The time course of sugars, organic acids and pH were measured. Available sugars
were consumed by L. plantarum producing up to 8.3 g L(-1) of lactic acid. Lactic
acid changed the pH from 3.9 to 3.4 after 14 days post-inoculation without
yielding a relevant concentration of acetic acid (0.34 g L(-1)).
PMID- 26437639
TI - [Not Available].
PMID- 26437638
TI - Taxonomic characterisation of Proteus terrae sp. nov., a N2O-producing, nitrate
ammonifying soil bacterium.
AB - In the context of studying the influence of N-fertilization on N2 and N2O flux
rates in relation to the soil bacterial community composition in fen peat
grassland, a group of bacterial strains was isolated that performed dissimilatory
nitrate reduction to ammonium and concomitantly produced N2O. The amount of
nitrous oxide produced was influenced by the C/N ratio of the medium. The
potential to generate nitrous oxide was increased by higher availability of
nitrate-N. Phylogenetic analysis based on the 16S rRNA and the rpoB gene
sequences demonstrated that the investigated isolates belong to the genus
Proteus, showing high similarity with the respective type strains of Proteus
vulgaris and Proteus penneri. DNA-DNA hybridization studies revealed differences
at the species level. These differences were substantiated by MALDI-TOF MS
analysis and several distinct physiological characteristics. On the basis of
these results, it was concluded that the soil isolates represent a novel species
for which the name Proteus terrae sp. nov. (type strain N5/687(T) =DSM 29910(T)
=LMG 28659(T)) is proposed.
PMID- 26437640
TI - Basigin-mediated redistribution of CD98 promotes cell spreading and
tumorigenicity in hepatocellular carcinoma.
AB - BACKGROUND: Dysregulated endocytosis of membrane proteins contributes
significantly to several hallmarks of cancer. Basigin can enhance cancer
progression, but its precise mechanism remains unclear. CD98 promotes cell
spreading and tumorigenicity by triggering integrin clustering and enhancing cell
adhesion to the extracellular matrix. The endocytosis and recyle of basigin and
CD98 might play critical roles in cancer. METHODS: The role of CD98 was confirmed
in liver cancer cells by cell spreading in vitro and tumorigenicity by nude mice
xenograft tumor assay in vivo; membrane expression of basigin and CD98 in SMMC
7721 was measured by FCAS; pull down and SPR analysis were uses to reveal the
direct association between basigin and CD98; DsRed1 tagged CD98 was blocked in
the cytoplasm in K7721 (whose basigin was knockn out) and had a well
colocalization with ER and Rab5a positive recycling endosomes under co-focal;
finally, by FRET imaging and FCAS we observed the internalization of basigin and
CD98 was flotillin-1-regulated, and their recycle at early steps was Arf6
mediated. RESULTS: Basigin and CD98 were highly expressed and co-localized on the
human hepatocellular carcinoma (HCC) cell membrane; basigin can directly bind to
CD98, mediating CD98 redistribution on the HCC cell membrane and activating the
downstream integrin signaling pathway. Internalization of basigin and CD98 was
flotillin-1 regulated the and their recycling was mediated by Arf6. This
recycling process for basigin and CD98 promotes cell spreading and tumor growth
in liver cancer xenografts. CONCLUSION: Basigin, as a redistribution chaperone of
CD98, plays a critical role in promoting cell spreading and the progression of
hepatocellular carcinoma.
PMID- 26437641
TI - Mass-Up: an all-in-one open software application for MALDI-TOF mass spectrometry
knowledge discovery.
AB - BACKGROUND: Mass spectrometry is one of the most important techniques in the
field of proteomics. MALDI-TOF mass spectrometry has become popular during the
last decade due to its high speed and sensitivity for detecting proteins and
peptides. MALDI-TOF-MS can be also used in combination with Machine Learning
techniques and statistical methods for knowledge discovery. Although there are
many software libraries and tools that can be combined for these kind of
analysis, there is still a need for all-in-one solutions with graphical user
friendly interfaces and avoiding the need of programming skills. RESULTS: Mass
Up, an open software multiplatform application for MALDI-TOF-MS knowledge
discovery is herein presented. Mass-Up software allows data preprocessing, as
well as subsequent analysis including (i) biomarker discovery, (ii) clustering,
(iii) biclustering, (iv) three-dimensional PCA visualization and (v)
classification of large sets of spectra data. CONCLUSIONS: Mass-Up brings
knowledge discovery within reach of MALDI-TOF-MS researchers. Mass-Up is
distributed under license GPLv3 and it is open and free to all users at
http://sing.ei.uvigo.es/mass-up.
PMID- 26437643
TI - Recent advance in molecular angiogenesis in glioblastoma: the challenge and hope
for anti-angiogenic therapy.
AB - Glioblastoma (GBM) is the most highly malignant brain tumor in the human central
nerve system. In this paper, we review new and significant molecular findings on
angiogenesis and possible resistance mechanisms. Expression of a number of genes
and regulators has been shown to be upregulated in GBM microvessel cells, such as
interleukin-8, signal transducer and activator of transcription 3, Tax
interacting protein-1, hypoxia induced factor-1 and anterior gradient protein 2.
The regulator factors that may strongly promote angiogenesis by promoting
endothelial cell metastasis, changing the microenvironment, enhancing the ability
of resistance to anti-angiogenic therapy, and that inhibit angiogenesis are
reviewed. Based on the current knowledge, several potential targets and
strategies are proposed for better therapeutic outcomes, such as its mRNA
interference of DII4-Notch signaling pathway and depletion of b1 integrin
expression. We also discuss possible mechanisms underlying the resistance to anti
angiogenesis and future directions and challenges in developing new targeted
therapy for GBM.
PMID- 26437644
TI - Are commercial probiotics and prebiotics effective in the treatment and
prevention of honeybee nosemosis C?
AB - The study was conducted to investigate the effect of Lactobacillus rhamnosus (a
commercial probiotic) and inulin (a prebiotic) on the survival rates of honeybees
infected and uninfected with Nosema ceranae, the level of phenoloxidase (PO)
activity, the course of nosemosis, and the effect on the prevention of nosemosis
development in bees. The cells of L. rhamnosus exhibited a high rate of survival
in 56.56 % sugar syrup, which was used to feed the honeybees. Surprisingly,
honeybees fed with sugar syrup supplemented with a commercial probiotic and a
probiotic + prebiotic were more susceptible to N. ceranae infection, and their
lifespan was much shorter. The number of microsporidian spores in the honeybees
fed for 9 days prior to N. ceranae infection with a sugar syrup supplemented with
a commercial probiotic was 25 times higher (970 million spores per one honeybee)
than in a control group fed with pure sucrose syrup (38 million spores per one
honeybee). PO activity reached its highest level in the hemolymph of this
honeybee control group uninfected with N. ceranae. The addition of probiotics or
both probiotics and prebiotics to the food of uninfected bees led to the ~2-fold
decrease in the PO activity. The infection of honeybees with N. ceranae
accompanied an almost 20-fold decrease in the PO level. The inulin supplemented
solely at a concentration of 2 MUg/mL was the only administrated factor which did
not significantly affect honeybees' survival, the PO activity, or the nosemosis
infection level. In conclusion, the supplementation of honeybees' diet with
improperly selected probiotics or both probiotics and prebiotics does not prevent
nosemosis development, can de-regulate insect immune systems, and may
significantly increase bee mortality.
PMID- 26437646
TI - New insights into diagnosis of Platynosomum fastosum (Trematoda: Dicrocoeliidae)
in cats.
AB - Platynosomum fastosum is a hepatic trematode which causes the so-called lizard
poisoning in cats. This parasite is reported in tropical and sub-tropical areas
infecting the liver, gallbladder, and bile ducts of cats. Despite its clinical
importance, the diagnosis of P. fastosum has been poorly investigated so far. In
this study, three cases of infection by P. fastosum in cats are reported. The
FLOTAC technique was utilized for the first time in the detection of eggs of this
parasite. Three cats (two males and one female), being one of them with a history
of diarrhea and vomiting, were diagnosed positive for the presence of P. fastosum
eggs through the FLOTAC technique. In conclusion, this study provides important
and new insights into the diagnosis of P. fastosum in cats, expanding the
geographical knowledge of this parasite in Brazil.
PMID- 26437645
TI - Molecular cloning and characterization of a Spirometra erinacei casein kinase I.
AB - The Spirometra erinacei casein kinase I (SeCKI) gene was cloned and expressed in
Escherichia coli, and its characteristics were investigated in this study. The
recombinant SeCP protein (rSeCKI) was purified. The vaccination of mice with
rSeCKI induced the Th1/Th2-mixed type of immune response with Th2 predominant
(high levels of IgG1). Western blotting analysis showed that rSeCP was recognized
by the sera of plerocercoid-infected mice, and anti-rSeCP serum recognized the
native SeCP protein of plerocercoid crude antigens. Transcription and expression
of SeCP was observed at the plerocercoid and adult stages of S. erinacei.
Immunolocalization identified SeCKI in the tegument and parenchymal tissues of
plerocercoids and in the teguments of adults. SeCKI appeared to be essential
indispensable for the S. erinacei development and survival in host, but its
biological functions need to be further investigated.
PMID- 26437647
TI - Magnetic resonance examination to predict pathological complete response
following neoadjuvant chemotherapy: when is it appropriate for HER2-positive and
triple-negative breast cancers?
AB - BACKGROUND: To clarify appropriate timing for magnetic resonance examination to
predict pathological complete response to neoadjuvant chemotherapy for patients
with human epidermal growth factor receptor 2 (HER2)-positive and triple-negative
breast cancers in terms of tumor volume change. METHODS: Between September 2009
and December 2014, 113 women with HER2-positive (n = 51) and triple-negative (n =
62) invasive breast cancers undergoing neoadjuvant chemotherapy were enrolled.
Patients with HER2-positive tumors underwent neoadjuvant chemotherapy with an
anthracycline-based regimen followed by docetaxel with trastuzumab. Patients with
triple-negative tumors underwent neoadjuvant chemotherapy with anthracycline
based (first in most cases) and taxane-based regimens. Magnetic resonance imaging
was performed before neoadjuvant chemotherapy, between the regimens (midpoint
examination), and after neoadjuvant chemotherapy (final examination). Response
ratio of tumor volume was calculated and receiver-operating characteristic
analyses for them for both subtypes were performed at the midpoint and final
examinations. RESULTS: Twenty-eight women with HER2-positive tumors (54.9 %) and
29 women with triple-negative tumors (46.8 %) had pathological complete response.
The response ratios were better in cases with pathological complete response than
in those without (p = 0.0341, p < 0.0001). The area under the curve at the final
examination was higher than that at the midpoint examination for HER2-positive
tumors (p = 0.039); whereas for the triple-negative tumors, no significant
difference between the two examinations was shown (p = 0.5218). CONCLUSIONS:
Magnetic resonance examination to predict pathological complete response would be
feasible after completion of a regimen including trastuzumab for HER2-positive
tumors and at the midpoint of neoadjuvant chemotherapy for triple-negative
tumors.
PMID- 26437648
TI - A dense SNP genetic map constructed using restriction site-associated DNA
sequencing enables detection of QTLs controlling apple fruit quality.
AB - BACKGROUND: Genetic map based quantitative trait locus (QTL) analysis is an
important method for studying important horticultural traits in apple. To
facilitate molecular breeding studies of fruit quality traits in apple, we aim to
construct a high density map which was efficient for QTL mapping and possible to
search for candidate genes directly in mapped QTLs regions. METHODS: A total of
1733 F1 seedlings derived from 'Jonathan' * 'Golden Delicious' was used for the
map constructionand QTL analysis. The SNP markers were developed by restriction
site-associated DNA sequencing (RADseq). Phenotyping data of fruit quality traits
were calculated in 2008-2011. Once QTLs were mapped, candidate genes were
searched for in the corresponding regions of the apple genome sequence underlying
the QTLs. Then some of the candidate genes were validated using real-time PCR.
RESULTS: A high-density genetic map with 3441 SNP markers from 297 individuals
was generated. Of the 3441 markers, 2017 were mapped to 'Jonathan' with a length
of 1343.4 cM and the average distance between markers was 0.67 cM, 1932 were
mapped to 'Golden Delicious' with a length of 1516.0 cM and the average distance
between markers was 0.78 cM. Twelve significant QTLs linked to the control of
fruit weight, fruit firmness, sugar content and fruit acidity were mapped to
seven linkage groups. Based on gene annotation, 80, 64 and 17 genes related to
fruit weight, fruit firmness and fruit acidity, respectively, were analyzed.Among
the 17 candidate genes associated with control of fruit acidity, changes in the
expression of MDP0000582174 (MdMYB4) were in agreement with the pattern of
changes in malic acid content in apple during ripening, and the relative
expression of MDP0000239624 (MdME) was significantly correlated withfruit
acidity. CONCLUSIONS: We demonstrated the construction of a dense SNP genetic map
in apple using next generation sequencing and that the increased resolution
enabled the detection of narrow interval QTLs linked to the three fruit quality
traits assessed. The candidate genes MDP0000582174 and MDP0000239624 were found
to be related to fruit acidity regulation. We conclude that application of RADseq
for genetic map construction improved the precision of QTL detection and should
be utilized in future studies on the regulatory mechanisms of important fruit
traits in apple.
PMID- 26437650
TI - Transdifferentiation of differentiated stem cells contributes to remyelination.
AB - Evidence suggests that transdifferentiation of mesenchymal stem cells (MSCs) into
various neuronal cells contributes to functional recovery after experimental
spinal cord injury. Qiu et al. have recently published an exciting article in
Stem Cell Research & Therapy demonstrating the transdifferentiation of already
differentiated MSCs that contributes to remyelination of injured/regenerating
axons, and thereby to functional recovery of spinal cord injured animals. The
authors highlight the importance of interaction between neurotrophin-3 and
tropomyosin receptor kinase C for the observed effects. This study provided
important evidence that manipulation of rat bone marrow-derived MSCs before
transplantation could enhance the therapeutic benefit of cell-based treatment.
PMID- 26437649
TI - Abdominal fat depots associated with insulin resistance and metabolic syndrome
risk factors in black African young adults.
AB - BACKGROUND: Individuals of black African ethnicity tend to have less visceral
adipose tissue (VAT) but more subcutaneous-abdominal adipose tissue (SCAT) than
white Caucasians. However, it is unclear whether such distribution of abdominal
fat is beneficial for metabolic disease risk in black individuals. Here we
compared the associations between these specific abdominal fat depots, insulin
sensitivity and metabolic syndrome risk. METHODS: A cross-sectional analysis of
76 black South African young adults (36 men; 40 women) aged 18-19 years
participating in the Birth to Twenty Cohort Study had VAT and SCAT measured by
MRI. The metabolic syndrome traits (blood pressure, lipid profile, fasting
glucose and insulin) were measured and the values were combined into a metabolic
syndrome risk score. Fasting glucose and insulin were used to derive the HOMA
index of insulin resistance (HOMA-IR). RESULTS: Compared to men, women had
greater VAT (mean: 16.6 vs. 12.5 cm(2)) and SCAT (median 164.0 vs. 59.9 cm(2)).
In men, SCAT (r = 0.50) was more strongly correlated to the metabolic syndrome
score (MetS) than was VAT (r = 0.23), and was associated with both MetS (P =
0.001) and HOMA-IR (P = 0.001) after adjustment for VAT and total fat mass. In
women, both abdominal fat compartments showed comparable positive correlations
with MetS (r = 0.26 to 0.31), although these trends were weaker than in men.
CONCLUSIONS: In young black South African adults, SCAT appears to be more
relevant than VAT to metabolic syndrome traits.
PMID- 26437651
TI - Blood cultures taken from patients attending emergency departments in South
Africa are an important antibiotic stewardship tool, which directly influences
patient management.
AB - BACKGROUND: Febrile illness with suspected blood stream infection (BSI) is a
common reason for admission to hospital in Africa and blood cultures are
therefore an important investigation. Data on the prevalence and causes of
community acquired BSI in Africa are scarce and there are no studies from South
Africa. There are no validated clinical prediction rules for use of blood
cultures in Africa. METHODS: A prospective observational cohort study of patients
attending 2 urban emergency departments in Cape Town, South Africa. The decision
to take a blood culture was made by the attending clinician and information
available at the time of blood draw was collected. Bottles were weighed to
measure volume of blood inoculated. RESULTS: 500 blood culture sets were obtained
from 489 patients. 39 (7.8 %) were positive for pathogens and 13 (2.6 %) for
contaminants. Significant independent predictors of positive cultures were
diastolic blood pressure <60 mmHg, pulse >120 bpm, diabetes and a suspected
biliary source of infection, but not HIV infection. Positive results influenced
patient management in 36 of 38 (95 %) cases with the organism being resistant to
the chosen empiric antibiotic in 9 of 38 (24 %). Taking <8 ml of blood was
predictive of a negative culture. The best clinical prediction rule had a
negative predictive value (NPV) of 92 % which is unlikely to be high enough to be
clinically useful. DISCUSSION: Blood cultures taken from patients attending
emergency departments in a high HIV prevalent city in South Africa are frequently
positive and almost always influence patient management. At least 8 ml of blood
should be inoculated into each bottle. CONCLUSION: Blood cultures should be taken
from all patients attending EDs in South Africa suspected of having BSI
particularly if diabetic, with hypotension, tachycardia or if biliary sepsis is
suspected.
PMID- 26437653
TI - MBE Growth of AlN Nanowires on Si Substrates by Aluminizing Nucleation.
AB - By introducing an aluminization process to achieve nucleation of nanowires (NWs),
spontaneous growth of AlN NWs on Si substrates has been realized by plasma
assisted molecular beam epitaxy. The AlN NWs are grown from the nuclei formed by
the aluminization process, and the NW density and diameter can be controlled by
the aluminization parameters. The influence of growth conditions on the
morphologies of AlN NWs is carefully investigated. Island-like films are found to
grow between the NWs due to poor migration ability of Al adatoms. The films are
proved to be Al-polar different from the N-polar AlN NWs, which can explain the
absence of newly formed NWs. Increasing the V/III ratio can efficiently suppress
the growth of Al-polar AlN films.
PMID- 26437652
TI - Simian malaria in wild macaques: first report from Hulu Selangor district,
Selangor, Malaysia.
AB - BACKGROUND: Malaria is a vector-borne parasitic disease which is prevalent in
many developing countries. Recently, it has been found that Plasmodium knowlesi,
a simian malaria parasite can be life-threatening to humans. Long-tailed
macaques, which are widely distributed in Malaysia, are the natural hosts for
simian malaria, including P. knowlesi. The aim of the present study was to
determine the prevalence of simian malaria parasites in long-tailed macaques in
the district of Hulu Selangor, Selangor, Malaysia. METHODS: A total of 70 blood
samples were collected from Macaca fascicularis dwelling in the forest of Hulu
Selangor by the Department of Wildlife and National Parks Peninsular Malaysia,
Kuala Lumpur, Malaysia. DNA was extracted using PureLinkTM Genomic DNA Kits.
Conventional and nested PCR were used to detect the genus and species of
Plasmodium parasites respectively. In addition, phylogenetic analysis was carried
out to confirm the species of Plasmodium parasites. RESULTS: Thirty-five (50 %)
of the 70 samples were positive for Plasmodium using genus-specific primers.
These positive samples were then subjected to nested PCR targeting the 18S
ribosomal RNA genes to detect all five simian malaria parasites: namely, P.
knowlesi, Plasmodium inui, Plasmodium cynomolgi, Plasmodium fieldi, and
Plasmodium coatneyi. All five species of simian malaria parasites were detected.
Of these, P. inui was the predominant (65.7 %), followed by P. knowlesi (60 %),
P. cynomolgi (51.4 %) P. coatneyi (45.7 %) and P. fieldi (2.9 %). A total of nine
macaques had mono-infection with P. knowlesi (four), P. cynomolgi (two), P.
coatneyi (two) and P. fieldi (one). Eleven of the macaques had dual infections
while 12 had triple infections. Three macaques were infected with four species of
Plasmodium. Molecular and phylogenetic analysis confirmed the five species of
Plasmodium parasites. CONCLUSION: This study has provided evidence to elucidate
the presence of transmission of malaria parasites among the local macaques in
Hulu Selangor. Since malaria is a zoonosis, it is important to determine the new
control strategies for the control of malaria.
PMID- 26437654
TI - Fabrication and Characterization of Monodisperse Magnetic Porous Nickel
Microspheres as Novel Catalysts.
AB - A facile and efficient hard-templating strategy is reported for the preparation
of porous nickel microspheres with excellent uniformity and strong magnetism. The
strategy involves impregnation of porous polymer microspheres with nickel
precursors, calcination to remove the template, followed by thermal reduction.
The morphology, structure, and the property of the Ni microspheres were
characterized by scanning electron microscopy, X-ray powder diffraction, N2
adsorption-desorption isotherms, thermogravimetric analysis, and magnetic
hysteresis measurement. The obtained porous nickel microspheres were
monodispersed with a particle size of 0.91 MUm and crystallite size of 52 nm.
Their saturation magnetization was much higher than that of Ni nanoparticles. The
unique porous nanostructured Ni microspheres possess catalytic activity and
excellent recyclability, as demonstrated in the catalytic reduction of 4
nitrophenol to 4-aminophenol. The micropherical Ni catalysts could be easily
separated either by an external magnetic field or by simple filtration.
PMID- 26437655
TI - Synthesis of BiPO4/Bi2S3 Heterojunction with Enhanced Photocatalytic Activity
under Visible-Light Irradiation.
AB - BiPO4/Bi2S3 photocatalysts were successfully synthesized by a simple two-step
hydrothermal process, which involved the initial formation of BiPO4 rod and then
the attachment of Bi2S3 through ion exchange. The as-synthesized products were
characterized by X-ray diffraction (XRD), scanning electron microscope (SEM),
transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS),
and UV-vis diffuse reflectance spectra (UV-vis DRS). It was found that BiPO4 was
regular rods with smooth surfaces. However, BiPO4/Bi2S3 heterojunction had a
rough surface, which could be attributed to the attachment of Bi2S3 on the
surface of BiPO4 rods. The BiPO4/Bi2S3 composite exhibited better photocatalytic
performance than that of pure BiPO4 and Bi2S3 for the degradation of methylene
blue (MB) and Rhodamine B (RhB) under visible light. The enhanced photocatalytic
performance could be ascribed to synergistic effect of BiPO4/Bi2S3
heterojunction, in which the attached Bi2S3 nanoparticles could improve visible
light absorption and the BiPO4/Bi2S3 heterojunction suppressed the recombination
of photogenerated electron-hole pairs. Our work suggested that BiPO4/Bi2S3
heterojunction could be a potential photocatalyst under visible light.
PMID- 26437656
TI - Conductivity of PEDOT:PSS on Spin-Coated and Drop Cast Nanofibrillar Cellulose
Thin Films.
AB - Aqueous dispersion of conductive polymer poly(3,4-ethylenedioxythiophene)
poly(styrenesulfonate) ( PEDOT: PSS) was deposited on spin-coated and drop cast
nanofibrillar cellulose (NFC)-glycerol (G) matrix on a glass substrate. A thin
glycerol film was utilized on plasma-treated glass substrate to provide adequate
adhesion for the NFC-glycerol (NFC-G) film. The effects of annealing temperature,
the coating method of NFC-G, and the coating time intervals on the electrical
performance of the PEDOT: PSS were characterized. PEDOT: PSS on drop cast NFC-G
resulted in 3 orders of magnitude increase in the electrical conductivity
compared to reference PEDOT: PSS film on a reference glass substrate, whereas the
optical transmission was only slightly decreased. The results point out the
importance of the interaction between the PEDOT: PSS and the NFC-G for the
electrical and barrier properties for thin film electronics applications.
PMID- 26437657
TI - Mechanism of Electrochemical Deposition and Coloration of Electrochromic V2O5
Nano Thin Films: an In Situ X-Ray Spectroscopy Study.
AB - Electrochromic switching devices have elicited considerable attention because
these thin films are among the most promising materials for energy-saving
applications. The vanadium oxide system is simple and inexpensive because only a
single-layer film of this material is sufficient for coloration. Vanadium dioxide
thin films are fabricated by electrochemical deposition and cyclic voltammetry.
Chronoamperometric analyses have indicated that the thin V2O5 film demonstrates
faster intercalation and deintercalation of lithium ions than those of the thick
V2O5 film, benefiting the coloration rate. Despite substantial research on the
synthesis of vanadium oxides, the monitoring of electronic and atomic structures
during growth and coloration of such material has not been thoroughly examined.
In the present study, in situ X-ray absorption spectroscopy (XAS) is employed to
determine the electronic and atomic structures of V2O5 thin films during
electrochemical growth and then electrochromic coloration. In situ XAS results
demonstrate the growth mechanism of the electrodeposited V2O5 thin film and
suggest that its electrochromic performance strongly depends on the local atomic
structure. This study improves our understanding of the electronic and atomic
properties of the vanadium oxide system grown by electrochemical deposition and
enhances the design of electrochromic materials for potential energy-saving
applications.
PMID- 26437658
TI - Relationship between probability of future shoulder arthroplasty and outcomes of
arthroscopic debridement in patients with advanced osteoarthritis of glenohumeral
joint.
AB - BACKGROUND: Arthroscopic glenohumeral debridement for symptom control has shown
promising short term results in the young active population, when arthroplasty
may not be a practical option due to the recommended activity restrictions,
potential for complications and/or early wear, and a need for revision. The
purpose of this study was twofold: 1) to examine the impact of arthroscopic
debridement with or without subacromial decompression on clinical outcomes in
patients with severe glenohumeral osteoarthritis (OA), and 2) to explore the
differences in post-debridement outcomes between patients who eventually
progressed to arthroplasty vs. those who did not. The role of an active worker's
compensation claim was examined. METHODS: Prospectively collected data of
patients who were not good candidates for shoulder arthroplasty and had
subsequently undergone arthroscopic shoulder debridement were used for analysis.
Disability was measured using the relative Constant-Murley score (CMS), the
American Shoulder and Elbow Surgeon's (ASES) assessment form, pain free range of
motion (ROM), and strength. RESULTS: Fifty-six patients were included in the
final analysis. Eighteen (32 %) patients underwent arthroplasty surgery
(arthroplasty group) over a period of 11 years. The arthroplasty group was
comparable with the non-arthroplasty group prior to debridement but was more
disabled at post-debridement surgery follow-up, functioning at less than 50 % of
normal based on ASES, relative CMS, and active painfree ROM. In the multivariable
analysis, the post-debridement relative CMS was affected by having a compensation
claim and having a future arthroplasty. CONCLUSION: Arthroscopic debridement
improved clinical outcome in 68 % of patients suffering from advanced OA of
glenohumeral joint. Having less than 50 % of normal score in ASES, relative CMS
and painfree ROM post- debridement within a period of two years may be an
indication for future arthroplasty. Role of worker's compensation claims should
not be underestimated.
PMID- 26437660
TI - [Not Available].
PMID- 26437661
TI - Bioinformatic Characterization of Genes and Proteins Involved in Blood Clotting
in Lampreys.
AB - Lampreys and hagfish are the earliest diverging of extant vertebrates and are
obvious targets for investigating the origins of complex biochemical systems
found in mammals. Currently, the simplest approach for such inquiries is to
search for the presence of relevant genes in whole genome sequence (WGS)
assemblies. Unhappily, in the past a high-quality complete genome sequence has
not been available for either lampreys or hagfish, precluding the possibility of
proving gene absence. Recently, improved but still incomplete genome assemblies
for two species of lamprey have been posted, and, taken together with an
extensive collection of short sequences in the NCBI trace archive, they have made
it possible to make reliable counts for specific gene families. Particularly, a
multi-source tactic has been used to study the lamprey blood clotting system with
regard to the presence and absence of genes known to occur in higher vertebrates.
As was suggested in earlier studies, lampreys lack genes for coagulation factors
VIII and IX, both of which are critical for the "intrinsic" clotting system and
responsible for hemophilia in humans. On the other hand, they have three each of
genes for factors VII and X, participants in the "extrinsic" clotting system. The
strategy of using raw trace sequence "reads" together with partial WGS assemblies
for lampreys can be used in studies on the early evolution of other biochemical
systems in vertebrates.
PMID- 26437662
TI - Comparative study between M. oleifera and aluminum sulfate for water treatment:
case study Colombia.
AB - The world has a water deficit, mostly located in developing countries. For
example, in Colombia, water deficit is a major concern and it increases in rural
areas, where the rate of accessibility to drinking water is of 33.26% in 2005.
Since the 1970s, the most used technology for water purification is the
conventional physicochemical process. The most common coagulant used in this
process is aluminum sulfate (alum). This study focuses on a comparison between
Moringa oleifera seeds and alum for water treatment in different natural waters.
Results showed that M. oleifera removed 90% turbidity and alum 96% from water
samples from the tested natural brook. However, color removal for M. oleifera was
95 and 80.3% for alum. For water-polluted samples, both coagulants have shown
high efficiency (100%) in color and turbidity removal. Usage of natural
coagulants (i.e., M. oleifera) instead of chemical ones (i.e., alum) are more
convenient in rural areas where the economic situation and accessibility of those
products are key elements to maintain fresh water treatment standards.
Additionally, results demonstrated that high dosages M. oleifera did not affect
the optimal value in terms of color and turbidity removal. In rural and
developing countries, this is important because it does not require a
sophisticated dosing equipment.
PMID- 26437663
TI - Identification and characterization of a maize-associated mastrevirus in China by
deep sequencing small RNA populations.
AB - BACKGROUND: Maize streak Reunion virus (MSRV) is a member of the Mastrevirus
genus in the family Geminiviridae. Of the diverse and increasing number of
mastrevirus species found so far, only Wheat dwarf virus and Sweetpotato
symptomless virus 1 have been discovered in China. Recently, a novel, unbiased
approach based on deep sequencing of small interfering RNAs followed by de novo
assembly of siRNA, has greatly offered opportunities for plant virus
identification. METHODS: Samples collected from maize leaves was deep sequencing
for virus identification. Subsequently, the assay of PCR, rolling circle
amplification and Southern blot were used to confirm the presence of a
mastrevirus. RESULTS: Maize streak Reunion virus Yunnan isolate (MSRV
[China:Yunnan 06:2014], abbreviated to MSRV-YN) was identified from maize
collected from Yunnan Province, China, by small RNA deep sequencing. The complete
genome of this virus was ascertained as 2,880 nucleotides long by conventional
sequencing. A phylogenetic analysis showed it shared 96.3 % nucleotide sequence
identity with the isolate of Maize streak Reunion virus from La Reunion Island.
To our knowledge, this is the first identification of MSRV in China. Analyses of
the viral derived small interfering RNAs (vsiRNAs) profile showed that the most
abundant MSRV-YN vsiRNAs were 21, 22 and 24 nt long and biased for A and G at
their 5' terminal residue. There was a slightly higher representation of MSRV-YN
siRNAs derived from the virion-sense strand genome than the complementary-sense
strand genome. Moreover, MSRV-YN vsiRNAs were not uniformly distributed along the
genome, and hotspots were detected in the movement protein and coat protein
coding region. CONCLUSIONS: A mastrevirus MSRV-YN collected in Yunnan Province,
China, was identified by small RNA deep sequencing. This vsiRNAs profile derived
from MSRV-YN was characterized, which might contribute to get an insight into the
host RNA silencing defense induced by MSRV-YN, and provide guidelines on
designing antiviral strategies using RNAi against MSRV-YN.
PMID- 26437665
TI - Sympatric ecological divergence associated with a color polymorphism.
AB - BACKGROUND: Color polymorphisms are a conspicuous feature of many species and a
way to address broad ecological and evolutionary questions. Three potential major
evolutionary fates of color polymorphisms are conceivable over time: maintenance,
loss, or speciation. However, the understanding of color polymorphisms and their
evolutionary implications is frequently impaired by sex-linkage of coloration,
unknown inheritance patterns, difficulties in phenotypic characterization, and a
lack of evolutionary replicates. Hence, the role of color polymorphisms in
promoting ecological and evolutionary diversification remains poorly understood.
In this context, we assessed the ecological and evolutionary consequences of a
color polymorphic study system that is not hampered by these restrictions: the
repeated adaptive radiations of the gold/dark Midas cichlid fishes (the
Amphilophus citrinellus species complex) from the great lakes and crater lakes of
Nicaragua, Central America. RESULTS: We conducted multi-trait morphological and
ecological analyses from ten populations of this young adaptive radiation (<6,000
years old), which revealed sympatric ecological differentiation associated with
the conspicuous binary (gold/dark) color polymorphism. Varying degrees of
intraspecific ecological divergence were observed across the ten color morph
pairs, but most pairs exhibited a consistently parallel ecological and
evolutionary trajectory across populations. Specifically, gold Midas cichlids are
frequently deeper-bodied, have more robust pharyngeal jaws, and feed at a lower
trophic level compared to conspecific, sympatric dark individuals. A common
garden experiment suggests there is a genetic correlation of color and eco
morphological traits. CONCLUSIONS: We demonstrate unprecedented ecological and
evolutionary consequences of color polymorphism in this adaptive radiation.
Across the species complex, sympatric conspecific individuals differed in eco
morphology depending on color morph (gold/dark) and the axis of differentiation
tended to be consistent across replicates. The consistent divergence across wild
populations and the common garden experiment suggests that color is genetically
correlated to ecology. Because Midas cichlids are known to mate color
assortatively, the putative genetic correlation of this color polymorphism with
an eco-morphological divergence suggests an innate potential to promote
ecological and evolutionary divergence across this species complex. However,
there are to date no examples of speciation based on color in this radiation,
suggesting long-term maintenance of this color polymorphism.
PMID- 26437666
TI - Is Noninvasive Brachial Systolic Blood Pressure an Accurate Estimate of Central
Aortic Systolic Blood Pressure?
AB - OBJECTIVES: Noninvasive brachial systolic blood pressure (nSBP-B) usually
approaches invasive central systolic blood pressure (iSBP-C) with a high
correlation. Whether nSBP-B is an accurate estimate of iSBP-C remained to be
investigated. Thus, this study aimed to compare the errors of nSBP-B and
noninvasive central systolic blood pressure (nSBP-C) with different techniques in
estimating iSBP-C. METHODS: Simultaneous invasive high-fidelity central aortic
pressure waveforms and the noninvasive left brachial pulse volume recording (PVR)
waveform were recorded in a Generation group ( N = 40) and a Validation group ( N
= 100). The accuracy of the noninvasive estimates of iSBP-C obtained from
analysis of the calibrated PVR waveform using the generalized transfer function
(GTF), pulse waveform analysis (PWA), and N-point moving average (NPMA) methods
was examined in the Validation group by calculating the mean absolute error
(MAE). RESULTS: In Generation group, the MAE was 4.6+/-4.1mm Hg between nSBP-B
and invasive brachial SBP, and 6.8+/-5.5mm Hg between nSBP-B and iSBP-C. In
comparison, the MAE of between iSBP-C and nSBP-C with PWA, NPMA, and GTF were
5.5+/-4.5, 5.8+/-4.9, and 5.9+/-5.0mm Hg, respectively. In Validation group, the
MAE of nSBP-B (6.9+/-4.6mm Hg) for estimating iSBP-C was significantly greater
than that of PWA (5.0+/-3.4mm Hg) and NPMA (6.1+/-4.4mm Hg), and GTF (6.1+/-4.9mm
Hg). The percentage of absolute band error <=5mm Hg was 62% for nSBP-B, 69% for
GTF, 83% for PWA, and 69% for NPMA. CONCLUSIONS: The accuracy of nSBP-B was
inferior to the n SBP-C measures in estimating iSBP-C.
PMID- 26437664
TI - Moderate-to-vigorous physical activity as a mediator between sedentary behavior
and cardiometabolic risk in Spanish healthy adults: a mediation analysis.
AB - BACKGROUND: Public health strategies for cardiovascular prevention highlight the
importance of physical activity, but do not consider the additional potentially
harmful effects of sedentary behavior. This study was conducted between 2010 and
2012 and analyzed between 2013 and 2014. The aim of the study was to analyze the
relationship between sedentary behavior and cardiometabolic risk factors in the
Spanish adult population and to examine whether this relationship is mediated by
moderate-to-vigorous physical activity (MVPA). METHODS: The cross-sectional study
included 1122 healthy subjects belonging to the EVIDENT study. Sedentary behavior
was objectively measured over 7 days using Actigraph accelerometers. We assessed
waist circumference (WC), triglycerides-to-HDL-C ratio (TG/HDL-C), and mean
arterial pressure (MAP), and undertook homeostasis model assessment (HOMA-IR).
Linear regression models were fitted according to Baron and Kenny procedures for
mediation analysis. RESULTS: TG/HDL-C and HOMA-IR were significantly higher in
adults who spent more minutes in sedentary activities after adjusting for
potential covariates. However when MVPA was added to the ANCOVA models as
covariate the effect of sedentary time on HOMA-IR disappeared. In addition, MVPA
acted as a full mediator of the relationship between sedentary time and HOMA-IR.
In contrast, subjects with lower levels of MVPA presented worse cardiometabolic
profiles than those from higher MVPA categories, even after controlling for
sedentary time and other potential confounders. CONCLUSIONS: These results
suggest that both MVPA and sedentary time should be considered when developing
cardiometabolic risk guidelines. TRIAL REGISTRATION: NCT01083082 .
PMID- 26437667
TI - Management and Outcomes of Esophageal Perforation: A National Study of 2,564
Patients in England.
AB - OBJECTIVES: Traditionally esophageal perforation is a rare clinical emergency
that confers a high rate of mortality and major morbidity. The objective of this
study was to establish the annual rate and mortality from esophageal perforation
and determine the effect of hospital volume on clinical outcomes. METHODS:
Hospital Episode Statistics database was used for the identification of patients
admitted to hospitals within England with esophageal perforation between 2001 and
2012. The influence of hospital volume and treatment approach upon clinical
outcomes was analyzed using multivariable analysis to control for patient age and
medical comorbidities that may influence outcome. RESULTS: Over the 12-year study
period 2,564 patients with esophageal perforation were treated at 158 hospitals.
The 30- and 90-day mortality rates were 30.0 and 38.8%, respectively. Esophageal
perforation etiology was spontaneous in 81.9% and iatrogenic in 5.9% of cases.
There was a significant increase in the percentage of patients managed
supportively and a reduction in surgical management over time. Furthermore there
were significant reductions in 30-day (36.6% to 24.9%; P<0.001) and 90-day
mortality (44.1% to 35.4%; P=0.006) over the 12-year study period. Important
patient demographics associated with 30- and 90-day mortality included age >=70
years, preoperative congestive cardiac failure, ischemic heart, liver, and renal
disease. High hospital volume was associated with significant reductions in 30-
(odds ratio (OR)=0.68; P=0.001) and 90-day mortality (OR=0.69; P=0.001). In a
subset analysis of patients undergoing endoscopic intervention, hospital volume
was identified as an important factor associated with mortality. CONCLUSIONS:
This study provides evidence for the centralization of management of esophageal
perforation to high volume centers with appropriate multi-disciplinary
infrastructure to treat these complex patients.
PMID- 26437668
TI - Charity condemns attack on Afghan hospital as "war crime".
PMID- 26437670
TI - Randomised comparison of two neonatal resuscitation bags in manikin ventilation.
AB - OBJECTIVE: To compare ventilation properties and user preference of a new upright
neonatal resuscitator developed for easier cleaning, reduced complexity, and
possibly improved ventilation properties, with the standard Laerdal neonatal
resuscitator. DESIGN: Eighty-seven Tanzanian and Norwegian nursing and medical
students without prior knowledge of newborn resuscitation were briefly trained in
bag-mask ventilation. The two resuscitators were used in random order on a
manikin connected to a test lung with normal or low lung compliance. Data were
collected with the Laerdal Newborn Resuscitation Monitor. The students graded
mask seal and ease of air entry on a four-point scale ranging from 1
('difficult') to 4 ('easy') and stated which device they preferred. (Equipment
from Laerdal Global Health and Laerdal Medical). RESULTS: For upright versus
standard resuscitator and normal lung compliance, mean expiratory lung volume was
15.5 mL vs 13.9 mL (p=0.001), mean mask leakage 48% vs 58% (p<0.001), and mean
airway pressure 20 cm H2O vs 19 cm H2O (p=0.003), respectively. For low lung
compliance, mean expiratory lung volume was 8.6 mL vs 8.1 mL (p=0.045), mean mask
leakage 53% vs 62% (p<0.001), and mean airway pressure 21 cm H2O vs 20 cm H2O
(p=0.004) for upright versus standard. The upright resuscitator was preferred by
82% and 68% of students during ventilation with normal and low lung compliance,
respectively (p=0.001). CONCLUSIONS: Expiratory volumes were higher, mask leakage
lower, and mean airway pressure slightly higher with upright versus standard
resuscitator when ventilating a manikin. The majority of students preferred the
upright resuscitator.
PMID- 26437669
TI - Global analysis of physical and functional RNA targets of hnRNP L reveals
distinct sequence and epigenetic features of repressed and enhanced exons.
AB - HnRNP L is a ubiquitous splicing-regulatory protein that is critical for the
development and function of mammalian T cells. Previous work has identified a few
targets of hnRNP L-dependent alternative splicing in T cells and has described
transcriptome-wide association of hnRNP L with RNA. However, a comprehensive
analysis of the impact of hnRNP L on mRNA expression remains lacking. Here we use
next-generation sequencing to identify transcriptome changes upon depletion of
hnRNP L in a model T-cell line. We demonstrate that hnRNP L primarily regulates
cassette-type alternative splicing, with minimal impact of hnRNP L depletion on
transcript abundance, intron retention, or other modes of alternative splicing.
Strikingly, we find that binding of hnRNP L within or flanking an exon largely
correlates with exon repression by hnRNP L. In contrast, exons that are enhanced
by hnRNP L generally lack proximal hnRNP L binding. Notably, these hnRNP L
enhanced exons share sequence and context features that correlate with poor
nucleosome positioning, suggesting that hnRNP may enhance inclusion of a subset
of exons via a cotranscriptional or epigenetic mechanism. Our data demonstrate
that hnRNP L controls inclusion of a broad spectrum of alternative cassette exons
in T cells and suggest both direct RNA regulation as well as indirect mechanisms
sensitive to the epigenetic landscape.
PMID- 26437671
TI - Efficacy of 1-methylcyclopropene on the mitigation of storage disorders of
"Rocha" pear under normal refrigerated and controlled atmospheres.
AB - Alternatives are needed for long-term preservation of European pears (Pyrus
communis L.) after the ban on diphenylamine. "Rocha" pear fruit harvested at
commercial maturity were treated with 1-methylcyclopropene (1-methylcyclopropene,
SmartFreshTM) and diphenylamine and stored at 0 C, 90-95% relative humidity,
under normal atmosphere for up to six months or under controlled atmosphere
(controlled atmosphere, 3 kPa O2 + 0.7 kPa CO2) for up to 9.4 months. At 312 nl
l(-1), 1-methylcyclopropene reduced softening and yellowing, and increased
soluble solids content during shelf life in comparison with fruit treated with
diphenylamine. 1-Methylcyclopropene at 312 nl l(-1) was also more effective than
diphenylamine in reducing superficial scald and internal browning disorders. 1
Methylcyclopropene at 150 nl l(-1) had little effect on ripening-related changes
but was effective against physiological disorders of pears stored in regular
atmosphere or under controlled atmosphere. Delayed controlled atmosphere slightly
reduced internal browning disorders but increased superficial scald. 1
Methylcyclopropene at 312 nl l(-1) reduced physiological disorders in "Rocha"
pear under refrigerated storage and delayed ripening-related softening and color
changes during shelf life. At 150 nl l(-1), 1-methylcyclopropene is as effective
as diphenylamine against storage disorders without ripening impairment.
PMID- 26437672
TI - Effects of nonthermal preservation technologies on antioxidant activity of fruits
and vegetables: A review.
AB - Consumer demand for safe and nutritious fruits and vegetables has given rise to
the development of a number of nonthermal food preservation techniques. Recent
studies have highlighted that antioxidant activity of fruits and vegetables plays
an important role in human health. In this paper, the influences of nonthermal
preservation technologies, including pulsed electric field, radiation processing,
dense phase carbon dioxide, ozone processing, and edible coatings, on the
antioxidant capacity and related compounds in fruits and vegetables are reviewed.
The proposed mechanisms and future trends are also discussed to accelerate the
further commercialization and exploration of these novel technologies, which
will, in turn, help to promote human health.
PMID- 26437673
TI - Interprotein Coupling Enhances the Electrocatalytic Efficiency of Tobacco
Peroxidase Immobilized at a Graphite Electrode.
AB - Covalent immobilization of enzymes at electrodes via amide bond formation is
usually carried out by a two-step protocol, in which surface carboxylic groups
are first activated with the corresponding cross-coupling reagents and then
reacted with protein amine groups. Herein, it is shown that a modification of the
above protocol, involving the simultaneous incubation of tobacco peroxidase and
the pyrolytic graphite electrode with the cross-coupling reagents produces higher
and more stable electrocatalytic currents than those obtained with either
physically adsorbed enzymes or covalently immobilized enzymes according to the
usual immobilization protocol. The remarkably improved electrocatalytic
properties of the present peroxidase biosensor that operates in the 0.3 V <= E <=
0.8 V (vs SHE) potential range can be attributed to both an efficient electronic
coupling between tobacco peroxidase and graphite and to the formation of intra-
and intermolecular amide bonds that stabilize the protein structure and improve
the percentage of anchoring groups that provide an adequate orientation for
electron exchange with the electrode. The optimized tobacco peroxidase sensor
exhibits a working concentration range of 10-900 MUM, a sensitivity of 0.08 A M(
1) cm(-2) (RSD 0.05), a detection limit of 2 MUM (RSD 0.09), and a good long-term
stability, as long as it operates at low temperature. These parameter values are
among the best reported so far for a peroxidase biosensor operating under simple
direct electron transfer conditions.
PMID- 26437674
TI - Effect of normal sperm morphology rate (NSMR) on clinical outcomes and
fertilization methods selection in the ultra-short-term GnRH-a protocol.
AB - PURPOSE: To investigate whether intracytoplasmic sperm injection (ICSI) can
improve the clinical outcomes of the male patients with teratozoospermia in the
ultra-short term GnRH-a protocol. METHODS: Based on different normal sperm
morphology rate (NSMR), the patients were divided into three groups as follows:
NSMR = 0% group, 1% <=NSMR <4% group and NSMR >=4% group. Each group was compared
with two fertilization type of in-vitro fertilization (IVF) and ICSI separately.
Main outcomes compared were normal fertilization, high-quality embryo,
transferrable embryo, implantation, pregnancy and abortion rate. RESULTS: We
observed that the total clinical pregnancy rate in single cleavage-stage embryo
transfer (SET) group was significantly lower compared with double cleavage-stage
embryo transfer (DET) group (23.87% versus 40.08%; p < 0.001). There was no
significant difference in the aspects of female age, endometrial thickness,
infertility duration and the number of retrieved oocytes among three groups (p >
0.05). The normal fertilization, high-quality embryo, transferrable embryo,
implantation, pregnancy and abortion rate of IVF and ICSI showed no significant
difference among three groups (p > 0.05). CONCLUSION: ICSI cannot improve
clinical outcomes of the patients with teratozoospermia in the ultra-short term
GnRH-a protocol.
PMID- 26437675
TI - Recovery from Mild Traumatic Brain Injury in Previously Healthy Adults.
AB - This prospective longitudinal study reports recovery from mild traumatic brain
injury (MTBI) across multiple domains in a carefully selected consecutive sample
of 74 previously healthy adults. The patients with MTBI and 40 orthopedic
controls (i.e., ankle injuries) completed assessments at 1, 6, and 12 months
after injury. Outcome measures included cognition, post-concussion symptoms,
depression, traumatic stress, quality of life, satisfaction with life,
resilience, and return to work. Patients with MTBI reported more post-concussion
symptoms and fatigue than the controls at the beginning of recovery, but by 6
months after injury, did not differ as a group from nonhead injury trauma
controls on cognition, fatigue, or mental health, and by 12 months, their level
of post-concussion symptoms and quality of life was similar to that of controls.
Almost all (96%) patients with MTBI returned to work/normal activities (RTW)
within the follow-up of 1 year. A subgroup of those with MTBIs and controls
reported mild post-concussion-like symptoms at 1 year. A large percentage of the
subgroup who had persistent symptoms had a modifiable psychological risk factor
at 1 month (i.e., depression, traumatic stress, and/or low resilience), and at 6
months, they had greater post-concussion symptoms, fatigue, insomnia, traumatic
stress, and depression, and worse quality of life. All of the control subjects
who had mild post-concussion-like symptoms at 12 months also had a mental health
problem (i.e., depression, traumatic stress, or both). This illustrates the
importance of providing evidence-supported treatment and rehabilitation services
early in the recovery period.
PMID- 26437676
TI - Porcine 2', 5'-oligoadenylate synthetases inhibit Japanese encephalitis virus
replication in vitro.
AB - The 2', 5'-oligoadenylate synthetases (OAS) are antiviral proteins and several
isoforms have been identified as flavivirus-resistance biomarkers in human and
mouse. The expression kinetics and antiviral functions of porcine OAS family
(OAS1, OAS2, and OASL) in PK-15 cells following infection by Japanese
encephalitis virus (JEV) were evaluated in the present study. The endogenous
expression of the three OAS genes was efficiently induced by IFN-alpha treatment
in PK-15 cells. However, expression of pOAS1 and pOAS2 responded more quickly
than pOASL. Infection by JEV also induced the expression of the pOAS isoforms,
but at a significantly lower level than that observed following IFN-alpha
stimulation. Transient overexpression of pOASL and pOAS1 inhibited JEV
replication more efficiently than OAS2 overexpression. Interestingly, knockdown
of pOAS2 expression by siRNA treatment led to the highest increase in JEV
multiplication. Co-silencing of RNase L and each pOAS revealed that the anti-JEV
function of pOAS1 and pOAS2 were RNase L dependent, while the antiviral activity
of pOASL was not. In conclusion, all pOAS isoforms play a significant role in the
response to JEV infection, and are differentially induced by different stimuli.
The alternative pathways of antiviral activity stimulated by OASL require further
study.
PMID- 26437677
TI - Resveratrol Stimulates Hydrogen Sulfide (H2 S) Formation to Relax Murine Corpus
Cavernosum.
AB - INTRODUCTION: Resveratrol (RVT) found in red wine protects against erectile
dysfunction and relaxes penile tissue (corpus cavernosum) via a nitric oxide (NO)
independent pathway. However, the mechanism remains to be elucidated. Hydrogen
sulfide (H2 S) is a potent vasodilator and neuromodulator generated in corpus
cavernosum. AIMS: We investigated whether RVT caused the relaxation of mice
corpus cavernosum (MCC) through H2 S. METHODS: H2 S formation is measured by
methylene blue assay and vascular reactivity experiments have been performed by
DMT strip myograph in CD1 MCC strips. MAIN OUTCOME MEASURES: Endothelial NO
synthase (eNOS) inhibitor Nomega-Nitro-L-arginine (L-NNA, 0.1 mM) or H2 S
inhibitor aminooxyacetic acid (AOAA, 2 mM) which inhibits both cystathionine-beta
synthase (CBS) and cystathionine-gamma-lyase (CSE) enzyme or combination of AOAA
with PAG (CSE inhibitor) has been used in the presence/absence of RVT (0.1 mM, 30
min) to elucidate the role of NO or H2 S pathways on the effects of RVT in MCC.
Concentration-dependent relaxations to RVT, L-cysteine, sodium hydrogen sulfide
(NaHS) and acetylcholine (ACh) were studied. RESULTS: Exposure of murine corpus
cavernosum to RVT increased both basal and L-cysteine-stimulated H2 S formation.
Both of these effects were reversed by AOAA but not by L-NNA. RVT caused
concentration-dependent relaxation of MCC and that RVT-induced relaxation was
significantly inhibited by AOAA or AOAA + PAG but not by L-NNA. L-cysteine caused
concentration-dependent relaxations, which are inhibited by AOAA or AOAA + PAG
significantly. Incubation of MCC with RVT significantly increased L-cysteine
induced relaxation, and this effect was inhibited by AOAA + PAG. However, RVT did
not alter the effect of exogenous H2 S (NaHS) or ACh-induced relaxations.
CONCLUSIONS: These results demonstrate that RVT-induced relaxation is at least
partly dependent on H2 S formation and acts independent of eNOS pathway. In
phosphodiesterase 5 inhibitor (PDE-5i) nonresponder population, combination
therapy with RVT may reverse erectile dysfunction via stimulating endogenous H2 S
formation.
PMID- 26437678
TI - Outcomes of total hip arthroplasty in patients with primary immune
thrombocytopenia.
AB - BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated acquired disease
that is characterized by a decrease in the platelet count and an increased risk
of bleeding. There is little information in the literature about the results of
major joint replacement surgery in patients with ITP. The aim of this study was
to report on the results of total hip arthroplasty (THA) in patients with primary
ITP. METHODS: We retrospectively identified 15 THAs performed in 11 patients with
primary ITP. The study group was matched (1:2) to a non-ITP control group of 30
THAs in 22 patients. According to the perioperative hematologic evaluation, blood
management interventions were performed. All procedures were performed by a
single surgeon and all patients received cementless components with ceramic-on
ceramic bearing. Mean duration of follow-up was 7.1 years (range, 2-13). RESULTS:
No significant differences were found between the two groups with regard to mean
operative time, intraoperative blood loss, amount of closed suction drainage,
length of hospital stay, and readmission rate. However, the proportion of
patients requiring transfusion of packed red blood cells and/or platelet
concentrate was higher in the ITP group when compared to the non-ITP group. Mean
Harris hip score improved from 49.5 points preoperatively to 93.4 points at the
final follow-up and no hips were revised for loosening or osteolysis in the ITP
group. No significant differences were found between the two groups with respect
to mean postoperative Harris hip scores and complication rates. CONCLUSIONS: Our
study showed encouraging clinical and radiographic results of THA in patients
with ITP without increased risk of adverse events compared to those in patients
without ITP. On the basis of these findings, we suggest that modern cementless
THA might be a viable treatment for achieving functional improvement in patients
with ITP and end-stage hip disease.
PMID- 26437679
TI - Discrete Rectangles, Prisms, and Heterometallic Cages from a Conjugated Cp*Rh
Based Building Block.
AB - By carefully selecting an existing synthetic strategy and suitable coordination
subunits, constructing desired coordination geometries is no longer that
difficult to accomplish. Herein, a new strategy to construct a series of
unprecedented structures by using conjugated Cp*Rh-based complex BN-OTf (Cp* =
eta(5)-C5Me5) as the building block is proposed. DFT calculations revealed
extensive delocalized pi bonds in the subunit. With BN-OTf, rectangular
macrocycles TN-bpy and TN-bpe were controllably synthesized. Single-crystal XRD
studies confirmed one-dimensional stacking channels for the tetranuclear
structure. Notably, the starting ligand imidazole-4,5-dicarboxylate was found to
act not only as a tetradentate but also as a hexadentate ligand that can
coordinate to further metal ions. Subsequently, [4 Rh+1 M] heterometallic
complexes HMZ (M = Cu and Zn) were accessed by chelating borderline hard/soft
Lewis acids. With TN-Linker or HMZ, two routes resulted in the [8 Rh+2 M]
heterometallic cages HMC (M = Cu and Zn) with excellent crystallinity and
stability. Surprisingly, when BN-OTf bonded to rhodium itself, triangular prisms
TP-Linker were obtained with high solubility after being linked by bipyridine
linkers. Both the X-ray structure and (1)H NMR spectrum confirmed the novel
isomerization of the triangular structures. All of the compounds were obtained in
high yields and were fully characterized by (1)H NMR spectroscopy, elemental
analysis, IR spectroscopy, and in most cases single-crystal X-ray structure
determination.
PMID- 26437680
TI - Determination of the potential gold electrowinning from an ammoniacal
thiosulphate solution applied to recycling of printed circuit board scraps.
AB - The use of electrochemical techniques in the selective recovery of gold from a
solution containing thiosulphate, ammonia, and copper, obtained from the leaching
of printed circuit boards from mobile phones using ammoniacal thiosulphate, are
shown in this work. First, cyclic voltammetry tests were performed to determine
the potential of electrodeposition of gold and copper, and then, electrowinning
tests at different potentials for checking the rates of recovery of these metals
were performed. The results of the cyclic voltammetry show that copper deposition
occurs at potentials more negative than -600 mV (Ag/AgCl), whereas the gold
deposition can be performed at potentials more positives than -600 mV (Ag/AgCl).
The results of electrowinning show that 99% of the gold present in solutions
containing thiosulphate and copper can be selectively recovered in a potential
range between -400 mV (vs Ag/AgCl) and -500 mV (vs Ag/AgCl). Furthermore, 99% of
copper can be recovered in potentials more negative than -700 mV (vs Ag/AgCl).
PMID- 26437681
TI - Developing models for the prediction of hospital healthcare waste generation
rate.
AB - An increase in the number of health institutions, along with frequent use of
disposable medical products, has contributed to the increase of healthcare waste
generation rate. For proper handling of healthcare waste, it is crucial to
predict the amount of waste generation beforehand. Predictive models can help to
optimise healthcare waste management systems, set guidelines and evaluate the
prevailing strategies for healthcare waste handling and disposal. However, there
is no mathematical model developed for Ethiopian hospitals to predict healthcare
waste generation rate. Therefore, the objective of this research was to develop
models for the prediction of a healthcare waste generation rate. A longitudinal
study design was used to generate long-term data on solid healthcare waste
composition, generation rate and develop predictive models. The results revealed
that the healthcare waste generation rate has a strong linear correlation with
the number of inpatients (R(2) = 0.965), and a weak one with the number of
outpatients (R(2) = 0.424). Statistical analysis was carried out to develop
models for the prediction of the quantity of waste generated at each hospital
(public, teaching and private). In these models, the number of inpatients and
outpatients were revealed to be significant factors on the quantity of waste
generated. The influence of the number of inpatients and outpatients treated
varies at different hospitals. Therefore, different models were developed based
on the types of hospitals.
PMID- 26437682
TI - The relationship between the Five-Factor Model personality traits and peptic
ulcer disease in a large population-based adult sample.
AB - The current study examined the relationship between the Five-Factor Model
personality traits and physician-confirmed peptic ulcer disease (PUD) diagnosis
in a large population-based adult sample, controlling for the relevant behavioral
and sociodemographic factors. Personality traits were assessed by participants
themselves and by knowledgeable informants using the NEO Personality Inventory-3
(NEO PI-3). When controlling for age, sex, education, and cigarette smoking, only
one of the five NEO PI-3 domain scales - higher Neuroticism - and two facet
scales - lower A1: Trust and higher C1: Competence - made a small, yet
significant contribution (p < 0.01) to predicting PUD in logistic regression
analyses. In the light of these relatively modest associations, our findings
imply that it is certain behavior (such as smoking) and sociodemographic
variables (such as age, gender, and education) rather than personality traits
that are associated with the diagnosis of PUD at a particular point in time.
Further prospective studies with a longitudinal design and multiple assessments
would be needed to fully understand if the FFM personality traits serve as risk
factors for the development of PUD.
PMID- 26437684
TI - Strong and superplastic nanoglass.
AB - The strength-ductility tradeoff has been a common long-standing dilemma in
materials science. For example, superplasticity with a tradeoff in strength has
been reported for Cu50Zr50 nanoglass (NG) with grain sizes below 5 nm. Here we
report an improvement in strength without sacrificing superplasticity in Cu50Zr50
NG by using a bimodal grain size distribution. Our results reveal that large
grains impart high strength, which is in striking contrast to the physical origin
of the improvement in strength reported in the traditional nanostructured
metals/alloys. Furthermore, the mechanical properties of NG with a bimodal
nanostructure depend critically upon the fraction of large grains. By increasing
the fraction of the large grains, a transition from superplastic flow to failure
by shear banding is clearly observed. We expect that these results will be useful
in the development of a novel strong and superplastic NG.
PMID- 26437683
TI - Epidemiology and genetics of cystic fibrosis in Asia: In preparation for the next
generation treatments.
AB - Cystic fibrosis (CF) in the Asian population is less frequently reported due to
under-diagnosis and lack of centralized CF patient registries. Clinical studies
on CF cases from Asia have documented a severe course of the disease. The
spectrum of the cystic fibrosis transmembrane conductance regulator (CFTR)
variants in this population is quite heterogeneous. In total, 166 variants have
been reported on approximately 3700 Asian CF chromosomes. The frequency of
F508del among Asians is low compared with Caucasians. Recent in vitro studies
have shown promise of small molecule correction and potentiation of 45 different
CFTR variants. Of these variants, 16 (including G551D and F508del) have also been
observed among Asian CF individuals. We suggest undertaking molecular studies
extensively to annotate CFTR variants that will help Asian CF individuals to
benefit from the precision medicine gaining momentum in the Western countries.
PMID- 26437685
TI - Stability of unstimulated and stimulated whole saliva flow rates in children.
AB - OBJECTIVE: To analyze the stability of the unstimulated saliva flow rate (USFR)
and the stimulated saliva flow rate (SSFR) in children followed from age 7 to 12
years old. METHODS: Longitudinal study. Whole saliva samples were collected from
school children (50 girls and 50 boys). Forty-four girls and 32 boys remained in
this cohort for 6 years (dropout rate 24%). Variables that could influence USFR
or SSFR patterns were analyzed in a repeated-measures manova. RESULTS: Over a 6
year follow-up, the children's USFR ranged from 0.41 to 0.46 mL/min in the
initial and final observation, respectively, and showed no significant
differences (P = 0.4455) during the follow-up. The children consistently belonged
to one of three distinct SSFR groups (P < 0.0001). A repeated-measures manova
model showed that USFR and SSFR were not associated with sex, body mass index, or
indoor temperature during sampling. CONCLUSION: These results indicate that USFR
and SSFR patterns were stable from 7 to 12 years old. This finding may be useful
in oral health prevention or treatment and in the search for biomarkers in saliva
for screening or diagnostic purposes.
PMID- 26437686
TI - Improved molecular diagnosis of the common recurrent intragenic deletion mutation
in IKBKG in a Filipino family with incontinentia pigmenti.
AB - Incontinentia pigmenti is a rare, multisystem X-linked dominant genetic disorder
caused by mutations in IKBKG, the encoding inhibitor of kappa light polypeptide
gene enhancer in B-cells. Almost 80% of all cases result from a recurrent
intragenic deletion mutation that removes exon 4-10. At present, this mutation
can be detected by a multi-primer polymerase chain reaction (PCR) technique
although current protocols may preferentially amplify the wild-type allele and
miss the deletion. Here, we report a female infant with incontinentia pigmenti
that also affected her mother and sister, and two spontaneously aborted male
siblings. We developed a modified PCR amplification method that provides more
robust detection of the exon 4-10 deletion mutation, which was demonstrated in
all affected females in this pedigree.
PMID- 26437687
TI - 'A short time but a lovely little short time': Bereaved parents' experiences of
having a child with spinal muscular atrophy type 1.
AB - AIM: Spinal muscular atrophy (SMA) type 1 is a relatively common, untreatable and
invariably fatal neuromuscular disorder of early childhood. Psychosocial care is
vital in management of families affected by this disease. There are few studies
examining the impact of having a family member with a neuromuscular disorder, and
none describing parents' experiences of having a child with SMA type 1. This
study explored parents' perspectives of having a child with SMA type 1, from
diagnosis to bereavement, in order to inform clinical practice by identifying
aspects most meaningful to parents and to aid development of support strategies.
METHODS: This qualitative study undertook thematic analysis of 11 in-depth
interviews with 13 bereaved parents of children with SMA type 1. RESULTS: While
individuals' experiences were unique, common themes emerging from the data
include: experiencing shock and anticipatory grief, processing feelings of
responsibility and helplessness, experiencing multiple losses including the loss
of future reproductive freedom, feeling supported, regaining a sense of control
by making decisions about the child's life and death, and finding peace in the
dying process. CONCLUSION: These findings highlight the importance of a
multidisciplinary approach to the care of such families, including psychosocial
support beginning from the time of diagnosis and continuing to bereavement. We
suggest areas for further exploration, with a goal to develop family-centred and
evidence-based psychosocial care guidelines to complement the current Standards
of Care for Spinal Muscular Atrophy.
PMID- 26437688
TI - Picosecond melting of peptide nanotubes using an infrared laser: a nonequilibrium
simulation study.
AB - Self-assembled functional peptide biomaterials are emerging with a wide range of
envisioned applications in the field of nanotechnology. Currently, methods and
tools have been developed to control and manipulate as well as to explore new
properties of self-assembled structures. However, considerably fewer studies are
being devoted to developing efficient methods to degrade or recycle such
extremely stable biomaterials. With this in mind, here we suggest a theoretical
framework, inspired by the recent developed mid-infrared free-electron laser
pulse technology, to dissociate peptide nanotubes. Adopting a diphenylalanine
channel as a prototypical example, we find that the primary step in the
dissociation process occurs due to the strong resonance between the carboxylate
bond vibrations of the diphenylalanine peptides and the tuned laser frequencies.
The effects of laser irradiation are determined by a balance between tube
formation and dissociation. Our work shows a proof of concept and should provide
a motivation for future experimental developments with the final aim to open a
new and efficient way to cleave or to recycle bio-inspired materials.
PMID- 26437689
TI - Streptocollin, a Type IV Lanthipeptide Produced by Streptomyces collinus Tu 365.
AB - Lanthipeptides are ribosomally synthesized and post-translationally modified
microbial secondary metabolites. Here, we report the identification and isolation
of streptocollin from Streptomyces collinus Tu 365, a new member of class IV
lanthipeptides. Insertion of the constitutive ermE* promoter upstream of the
lanthipeptide synthetase gene stcL resulted in peptide production. The
streptocollin gene cluster was heterologously expressed in S. coelicolor M1146
and M1152 with 3.5- and 5.5-fold increased yields, respectively. The structure
and ring topology of streptocollin were determined by high resolution MS/MS
analysis. Streptocollin contains four macrocyclic rings, with one lanthionine and
three methyllanthionine residues. To the best of our knowledge, this is the first
report on the isolation of a class IV lanthipeptide in preparative amounts, and
on the successful heterologous expression of a class IV lanthipeptide gene
cluster.
PMID- 26437690
TI - Developing ecological scenarios for the prospective aquatic risk assessment of
pesticides.
AB - The prospective aquatic environmental risk assessment (ERA) of pesticides is
generally based on the comparison of predicted environmental concentrations in
edge-of-field surface waters with regulatory acceptable concentrations derived
from laboratory and/or model ecosystem experiments with aquatic organisms. New
improvements in mechanistic effect modeling have allowed a better
characterization of the ecological risks of pesticides through the incorporation
of biological trait information and landscape parameters to assess individual,
population and/or community-level effects and recovery. Similarly to exposure
models, ecological models require scenarios that describe the environmental
context in which they are applied. In this article, we propose a conceptual
framework for the development of ecological scenarios that, when merged with
exposure scenarios, will constitute environmental scenarios for prospective
aquatic ERA. These "unified" environmental scenarios are defined as the
combination of the biotic and abiotic parameters that are required to
characterize exposure, (direct and indirect) effects, and recovery of aquatic
nontarget species under realistic worst-case conditions. Ideally, environmental
scenarios aim to avoid a potential mismatch between the parameter values and the
spatial-temporal scales currently used in aquatic exposure and effect modeling.
This requires a deeper understanding of the ecological entities we intend to
protect, which can be preliminarily addressed by the formulation of ecological
scenarios. In this article we present a methodological approach for the
development of ecological scenarios and illustrate this approach by a case-study
for Dutch agricultural ditches and the example focal species Sialis lutaria.
Finally, we discuss the applicability of ecological scenarios in ERA and propose
research needs and recommendations for their development and integration with
exposure scenarios. Integr Environ Assess Manag 2016;12:510-521. (c) 2015 SETAC.
PMID- 26437691
TI - Mechanistic Insight into a Sugar-Accelerated Tin-Catalyzed Cascade Synthesis of
alpha-Hydroxy-gamma-butyrolactone from Formaldehyde.
AB - Applications of the formose reaction, which involves the formation of sugars from
formaldehyde, have previously been confined to the selective synthesis of
unprotected sugars. Herein, it is demonstrated that alpha-hydroxy-gamma
butyrolactone (HBL), which is one of the most important intermediates in
pharmaceutical syntheses, can be produced from paraformaldehyde. In the developed
reaction system, homogeneous tin chloride exhibits high catalytic activity and
the addition of mono- and disaccharides accelerates the formation of HBL. These
observations suggest that the formose reaction may serve as a feasible pathway
for the synthesis of important chemicals.
PMID- 26437692
TI - Mechanistic Insight into the Facilitation of beta-Lactam Fragmentation through
Metal Assistance.
AB - The mechanism of OsH6(PiPr3)2-mediated fragmentation of a 4-(2 pyridyl)-2
azetidinone has been investigated by DFT calculations. The addition of the C4-H
bond of the substrate to OsH2(PiPr3)2 allows the active participation of an
osmium lone pair in the B-type beta-lactam fragmentation process. This new
mechanism makes the N1-C4/C2-C3 fragmentation of the lactamic core thermally
accessible through a stepwise process.
PMID- 26437693
TI - Synchronous del5q myelodysplastic syndrome (del5qMDS) and adult B-cell acute
lymphoblastic leukemia (B-ALL) with TET2 and TP53 mutations.
PMID- 26437694
TI - Fusion and planarization of bisBODIPY: a new family of photostable near infrared
dyes.
AB - We have synthesized a new family of directly-fused bisBODIPY BBP 1 through a key
FeCl3-mediated intramolecular oxidative cyclodehydrogenation reaction and its
derivatives 2 and 3 from the Knoevenagel reaction. These dyes display effective
expansion of pi-conjugation over the two BODIPYs due to their locked coplanar
conformation, showing intriguing electrochemical and spectroscopic properties,
such as intensive absorption/emission bands ranging from 676 to 877 nm and high
photostability.
PMID- 26437696
TI - [Stability of mortality from thyroid cancer in a developing country].
AB - OBJECTIVE: To establish characteristics and the trend of mortality from thyroid
cancer in Colombia. MATERIAL AND METHODS: This is a study of mortality from
thyroid cancer in Colombia using official national mortality databases (1998
2010). Year of death, sex, age and department of residence were analyzed.
Proportions, arithmetic mean and median were used. The p-value for statistical
significance was 0.05. Crude, specific and age-adjusted rates were calculated.
RESULTS: Overall, 2 570 people died of thyroid cancer; 1 827 (71.1 %) deaths
occurred in women. Median age at death was 68 years for men and 70 years for
women. The age-adjusted average annual mortality rate (2006-2010) for thyroid
cancer was 0.52 cancer deaths per 100 000 (both sexes), 0.32 deaths per 100 000
men and 0.70 per 100 000 women. CONCLUSIONS: Further studies showing potential
factors associated with earlier age at death among Colombian women should be
made.
PMID- 26437695
TI - Evaluation of a novel automated allergy microarray platform compared with three
other allergy test methods.
AB - Microarray platforms, enabling simultaneous measurement of many allergens with a
small serum sample, are potentially powerful tools in allergy diagnostics. We
report here the first study comparing a fully automated microarray system, the
Microtest allergy system, with a manual microarray platform, Immuno-Solid phase
Allergen Chip (ISAC), and two well-established singleplex allergy tests, skin
prick test (SPT) and ImmunoCAP, all tested on the same patients. One hundred and
three adult allergic patients attending the allergy clinic were included into the
study. All patients were tested with four allergy test methods (SPT, ImmunoCAP,
Microtest and ISAC 112) and a total of 3485 pairwise test results were analysed
and compared. The four methods showed comparable results with a positive/negative
agreement of 81-88% for any pair of test methods compared, which is in line with
data in the literature. The most prevalent allergens (cat, dog, mite, timothy,
birch and peanut) and their individual allergen components revealed an agreement
between methods with correlation coefficients between 0.73 and 0.95. All four
methods revealed deviating individual patient results for a minority of patients.
These results indicate that microarray platforms are efficient and useful tools
to characterize the specific immunoglobulin (Ig)E profile of allergic patients
using a small volume of serum sample. The results produced by the Microtest
system were in agreement with diagnostic tests in current use. Further data
collection and evaluation are needed for other populations, geographical regions
and allergens.
PMID- 26437697
TI - Healthcare plans and consumer perceptions of healthcare institutions.
AB - OBJECTIVE: This study evaluates the effect of healthcare insurance plans on
consumer perception of trust in a healthcare institution, and the mediating
effect of trust on consumer loyalty towards an institution. METHOD: The study was
conducted at a healthcare institution in Colombia where a total of 841 patients
responded to a questionnaire. RESULTS: A structural equation model shows that
individuals who have a pre-paid healthcare plan have a stronger evaluation of
trust compared to those who hold a regulated healthcare plan (i.e., subsidized
and contributory plans). In turn, trust positively predicts consumers' loyalty
towards an institution. The relationship between the patients' healthcare plans
and their degree of loyalty towards healthcare institutions is completely
mediated by their perception of trust towards the institution. DISCUSSION: A
greater perception of trust is explained by having a medical plan that provides
consumers with more flexibility, allowing them to select their health provider at
a premium price. Although health institutions do not control healthcare regimes,
these affect consumers' trust in their service. Institutions cannot modify
characteristics of the regime, but they can promote a trustworthy environment to
strengthen consumers' loyalty to the institution.
PMID- 26437698
TI - Hazards for Women and Children in Rural Settings.
AB - OBJECTIVES: a) To identify possible risk factors associated with rural accidents
in women, b) to describe women's knowledge about zoonosis, c) to describe women's
risk perception about farming, d) to describe mothers' risk perception about
children's activities in rural settings, e) to estimate the initial age of
exposure to the rural setting and its dangers, and f) to identify possible risk
factors associated with rural accidents in children. MATERIALS AND METHODS: Cross
sectional design. Women with children that live in the countryside were surveyed
(n=24). Structured questionnaire. STATISTICAL ANALYSES: chi2, Student's t-test,
Pearson's correlation coefficient and logistic regression. RESULTS: Many women
had suffered an accident in the countryside (65.6 %). Farm worker usually did not
use personal protective equipment (PPE). Hearing protection, gloves, and safety
goggles were rarely used. Working women showed a high risk perception for urban
driving, the handling of agrochemicals, and driving on main roads (85.7 %, 70 %
and 66.7 %). There was no significant association between risk perception and PPE
use. Most mothers (87.5 %) thought that was good for children to learn how to
perform farm chores starting at a young age. Children started to drive tractors
at 9 years of age; 12.23 years on average. More than 7 % of the children (7.14 %)
have suffered an accident on the farm. The most frequent accidents were being
trapped in machinery (60 %). No association was found between the independent
variables and the dependent variable; farm-related accidents in children (p>0.2).
CONCLUSIONS: Risk communication is necessary to inform people involved and to
reduce exposure.
PMID- 26437699
TI - [Analysis of the performance of the assessment battery related to psychosocial
factors in Colombia].
AB - OBJECTIVE: The goal of this study is to analyze the performance of the three
questionnaires and the file of general information that comprise the Set of
Instruments for the Assessment of Psychosocial Factors in six companies from
different economic sectors in Colombia, with regard to: (a) content of the
instruments, (b) application methodology, and (c) the response from workers and
employers. METHODOLOGY: This research was performed through the study of multiple
instances. It was based on the processing of: (1) the observation logs with
regard to the application of the questionnaires, (2) workers' annotations about
their questionnaires and (3) minutes of meetings with representatives of the
workers. A reclassification into more specific subcategories was done taking into
consideration some particular and common elements found between companies.
RESULTS: Regarding the "Content" category, there are significant limitations in
the questionnaires about both outside and inside-of-work factors. This is because
some items cannot be applied under specific working conditions such as
outsourcing or field work. In "Methodology" it was observed that some practices
could decrease the reliability of the assessments, such as not having adequate
schedules or locations. In the "Reception" category, it was found that even
though this assessment is deemed desirable by most workers and employers, there
are, however, some actions taken by companies that could affect this perception.
CONCLUSIONS: It is positive to implement the assessment of psychosocial working
conditions in companies of this country, even though this assessment, with a
universal assessment tool, has difficulties in a changing and increasingly
complex working world. It is advisable to complement these assessments with
qualitative methods.
PMID- 26437700
TI - [The interaction in clinical nursing education: reflections on care of the person
with hypertension].
AB - OBJECTIVE: To identify the knowledge and attitudes about self-care in health
among users who received clinical nursing education for hypertension based on the
level of knowledge and attitudes of the hypertensive patient through interactive
care interventions with patients and relatives in the therapeutic context, with
the goal of developing health education. METHOD: This study represents action
research with a qualitative approach on hypertensive patients hospitalized for
stroke. Hypertension as a risk factor is most strongly associated with the
development of this health problem. RESULTS: Participants were interviewed about
their knowledge about the illness before and after the realization of
individualized health education activities on the basis of the theory of symbolic
interactionism. CONCLUSION: It was found that the respondents, after
participating in the educational process, demonstrated a broader knowledge of
hypertension, which motivated them to seek changes in habits that could improve
their quality of life. Through the use of symbolic interactionism, health
education proved to be a strategy for empowerment and autonomy of the
hypertensive subject with respect to their treatment and can be integrated into
nursing care.
PMID- 26437701
TI - [Information technology in learning sign language].
AB - OBJECTIVE: To develop a technological tool that improves the initial learning of
sign language in hearing impaired children. METHODS: The development of this
research was conducted in three phases: the lifting of requirements, design and
development of the proposed device, and validation and evaluation device. Through
the use of information technology and with the advice of special education
professionals, we were able to develop an electronic device that facilitates the
learning of sign language in deaf children. This is formed mainly by a graphic
touch screen, a voice synthesizer, and a voice recognition system. Validation was
performed with the deaf children in the Filadelfia School of the city of Bogota.
RESULTS: A learning methodology was established that improves learning times
through a small, portable, lightweight, and educational technological prototype.
CONCLUSIONS: Tests showed the effectiveness of this prototype, achieving a 32 %
reduction in the initial learning time for sign language in deaf children.
PMID- 26437702
TI - [Risk factors related with pediatric accidents in a children's hospital in
Bogota].
AB - OBJECTIVE: To describe the biophysical and sociocultural risk factors related to
the accident rate in pediatric patients. METHOD: Cross-sectional descriptive
study. Data collection through the direct application of surveys. RESULTS: 308
surveys were analyzed, obtained between the months of february and april, 2010.
Adolescents were the most affected group (33.5 %); the male gender registered the
highest number of traumas (64.7 %). The main family type was nuclear 52 %, 34.9 %
of patients belonged to stratum 2 and 46,6 % were under the care of their mothers
when the accident occurred. 84 % of caretakers had over 5 years study, 47 %
considered that the most unsafe place for a child is a public road, and 76.8 %
stated having never received information on accident prevention. The most
frequent accident was a fall from a height (54.7 %) and home was the place with
highest number of traumas (51 %). DISCUSSION: Demographic features and
sociocultural factors of this study differ from reports from large studies of non
intentional lesions.
PMID- 26437703
TI - [Medicinal herbs used in the care for diseases of the digestive system in the
city of Taxco, Guerrero, Mexico].
AB - OBJECTIVE: This study shows a) the empirical use, b) the properties proven
scientifically and c), doses of the main medicinal herbs that are used in the
care for disease of the digestive system (and/or its signs and symptoms) in the
city of Taxco, Guerrero, Mexico. METHODS: The study was qualitative. Approaches
regarding sampling in qualitative research were taken into account. This
specifically was with regard to homogeneous samples. We interviewed six
recognized traditional practitioners that had deep knowledge of the subject. A
questionnaire interview with open questions was designed regarding the
characteristics of the major herbs, the most common diseases of the digestive
system, and the doses and parts used. RESULTS: The main findings reflect about 20
plants that are used to heal these conditions, as well as their real
scientifically proven health properties. CONCLUSIONS: Medicinal plants continue
to be part of a complex local medical structure. This knowledge and the set of
specialized therapeutic techniques and treatments are valid today.
PMID- 26437704
TI - [Tuberculosis and drug-resistance tuberculosis in prisoners. Colombia, 2010
2012].
AB - OBJECTIVE: To characterize tuberculosis drug-resistance using anti-tuberculosis
drug-sensitivity tests in Colombian prisoners. METHODS: Descriptive-retrospective
analyses were performed on cases of tuberculosis in prisoners. Samples were
evaluated by the National Reference Laboratory. Conditions like gender, TB/VIH co
infection and drug-resistance were evaluated. RESULTS: Anti-tuberculosis drug
sensitivity tests were carried out on 72 prisoners. Results showed a distribution
of 90.7 % of cases in males and 9.3 % of cases in females. 12 % of cases were
TB/VIH co-infections, 94 % of the cases had not received any anti-tuberculosis
treatment before, six isolates were drug-resistant corresponding to 8.8 % of
total cases, and two cases were multi drug-resistant representing 1.3 % of the
cases. Of the drug-resistant cases, 83.3 % were TB/VIH co-infected. Previously
treated cases corresponded to 5.6 % of the total cases analyzed. One case with
TB/VIH co-infection and rifampicin resistance was observed, representing 1.3 % of
the total cases. CONCLUSION: The government must create a clear policy for
prisoners in Colombia, because a high rate of disease in prisoners was observed.
In addition, the results showed an association between drug-resistance and TB/VIH
co-infection. Overcrowding and low quality of life in penitentiaries could become
an important public health problem.
PMID- 26437705
TI - [Antimicrobial susceptibility of Salmonella enterica isolated during the pre
harvest period in swine in Colombia].
AB - OBJECTIVE: To determine the antimicrobial susceptibility of isolates of
Salmonella enterica isolated from animals and during the pre-slaughter period.
METHOD: Antimicrobial susceptibility tests were performed using the agar
diffusion method on 333 isolates of Salmonella enterica obtained from the pre
harvest period represented by transport trucks and pens. From the animals,
isolates were obtained from the animals' feces in transport trucks and pens,
mesenteric lymph nodes, and cecal content. The specimens were obtained from four
slaughtering facilities. RESULTS: The antimicrobial susceptibility tests were
performed obtaining the following results: 99.6 % (n=332) of isolates showed
resistance to at least one antimicrobial agent. The following resistance
percentages were found: amoxicillin-clavulanic acid 15.9 % (n=53), ampicillin
33.9 % (n=113), ceftiofur 41.4 % (n=138), ciprofloxacin 9 % (n=30 ),
chloramphenicol 19.2 % (n=64), florfenicol 33 % (n=110), gentamicin 22.8 %
(n=76), sulfamethoxazole-trimethoprim 24.9 % (n=83), tetracycline 93.1 % (n=310)
and tilmicosin 73.8 % (n=246). CONCLUSION: The results show that it is essential
to reinforce containment measures to prevent the development of antimicrobial
resistances and improve training of the operators, workers, and veterinarians in
Colombia involved in the primary production, product processing, distribution,
and sale to the consumer, thereby guaranteeing a safe food product and the
effectiveness of antimicrobial agents in human and veterinary medicine.
PMID- 26437706
TI - Efficacy of the prescription of physical activity in the obese child population.
AB - OBJECTIVE: To determine the effectiveness of prescribing physical activity to the
population of overweight and obese children, in accordance with the levels of
evidence. METHODS: To find literature pertaining to the intervention of physical
activity in overweight and obese children. four electronic databases were used:
Pubmed, Embase, Cochrane and Lilacs. The search was conducted with a cut-off date
of June 2012. Randomized controlled clinical trials of intervention programs
involving physical activity for both overweight and obese children were selected.
Two independent researchers reviewed and evaluated the quality of the studies,
and extracted intervention and result data. RESULTS: A total of 204 studies were
identified. 19 randomized controlled studies which complied with inclusion and
exclusion criteria were included. These studies evaluated the impact of physical
activity among obese children and compared different types of intervention based
on exercise and diet or both with the objective of reducing weight in obese
children. CONCLUSIONs: It is necessary to conduct studies on obese children with
bigger sample sizes to determine the effects of the treatment, and more
importantly, to devise comprehensive programs that include a structured exercise
program complemented by a dietary program. Likewise, the development of public
health policies that allow for the development of national programs for weight
and obesity control in Colombian children and adults should be developed, taking
into account that the causes of obesity are multiple, including social, familiar,
metabolic, and dietary aspects.
PMID- 26437707
TI - [The value of dental imaging in the teaching and promotion of oral health].
AB - In the context of the great diversity of oral microflora, including over 600
species, we highlight the educational value of electron micrographs and images of
dental plaque cultures in dental models made with culture media, showing the
bacterial colonies in the anatomic sites of the teeth that were most abundantly
colonized. Such images allow for an easy understanding of the magnitude of the
oral microbiome for students of biomedical careers--especially dentistry--and for
the general public. As such, these images can be used in teaching programs and
oral health campaigns.
PMID- 26437708
TI - [The decade of action for road safety in Medellin, Colombia, to 2015].
AB - Road safety (RS) is key in the study and intervention of human mobility. It is a
determining priority in international public health and in the development of
communities and nations. The declaration of a global RS crisis in the 1990s by
the United Nations urged the social, political and technical processes to propose
the Decade of Action for Road Safety 2010-2020 (DARS). The DARS has a global
action plan structured around five pillars; the first refers to institutional
management. The article describes the background, framework, evidence, and
effects of poor management during first half of the DARS in Medellin, Colombia up
to 2015.
PMID- 26437709
TI - Impact of sympathetic nervous system activity on post-exercise flow-mediated
dilatation in humans.
AB - Transient reduction in vascular function following systemic large muscle group
exercise has previously been reported in humans. The mechanisms responsible are
currently unknown. We hypothesised that sympathetic nervous system activation,
induced by cycle ergometer exercise, would contribute to post-exercise reductions
in flow-mediated dilatation (FMD). Ten healthy male subjects (28 +/- 5 years)
undertook two 30 min sessions of cycle exercise at 75% HR(max). Prior to
exercise, individuals ingested either a placebo or an alpha1-adrenoreceptor
blocker (prazosin; 0.05 mg kg(-1)). Central haemodynamics, brachial artery shear
rate (SR) and blood flow profiles were assessed throughout each exercise bout and
in response to brachial artery FMD, measured prior to, immediately after and 60
min after exercise. Cycle exercise increased both mean and antegrade SR (P <
0.001) with retrograde SR also elevated under both conditions (P < 0.001). Pre
exercise FMD was similar on both occasions, and was significantly reduced (27%)
immediately following exercise in the placebo condition (t-test, P = 0.03). In
contrast, FMD increased (37%) immediately following exercise in the prazosin
condition (t-test, P = 0.004, interaction effect P = 0.01). Post-exercise FMD
remained different between conditions after correction for baseline diameters
preceding cuff deflation and also post-deflation SR. No differences in FMD or
other variables were evident 60 min following recovery. Our results indicate that
sympathetic vasoconstriction competes with endothelium-dependent dilator activity
to determine post-exercise arterial function. These findings have implications
for understanding the chronic impacts of interventions, such as exercise
training, which affect both sympathetic activity and arterial shear stress.
PMID- 26437710
TI - How Cryptococcus interacts with the blood-brain barrier.
AB - Cryptococcus demonstrates predilection for invasion of the brain, but the
mechanism by which Cryptococcus crosses the blood-brain barrier (BBB) to cause
brain invasion is largely unknown. In order for Cryptococcus to cross the BBB,
there must be a way to either cross human brain microvascular endothelial cells,
which are the main constitute of the BBB, or go in between tight junctions.
Recent evidence of human brain microvascular endothelial cell responses to
transcellular brain invasions includes membrane rearrangements, intracellular
signaling pathways and cytoskeletal activations. Several Cryptococcal genes
related to the traversal of BBB have been identified, including CPS1, ITR1a,
ITR3c, PLB1, MPR1, FNX1 and RUB1. In addition, Cryptococcus neoformans-derived
microvesicles may contribute to cryptococcal brain invasion. Paracellularly,
Cryptococcus may traverse across BBB using either routes utilizing plasmin,
ammonia or macrophages in a Trojan horse mechanism.
PMID- 26437711
TI - The Unexpected Influence of Precursor Conversion Rate in the Synthesis of III-V
Quantum Dots.
AB - Control of quantum dot (QD) precursor chemistry has been expected to help improve
the size control and uniformity of III-V QDs such as indium phosphide and indium
arsenide. Indeed, experimental results for other QD systems are consistent with
the theoretical prediction that the rate of precursor conversion is an important
factor controlling QD size and size distribution. We synthesized and
characterized the reactivity of a variety of group-V precursors in order to
determine if precursor chemistry could be used to improve the quality of III-V
QDs. Despite slowing down precursor conversion rate by multiple orders of
magnitude, the less reactive precursors do not yield the expected increase in
size and improvement in size distribution. This result disproves the widely
accepted explanation for the shortcoming of current III-V QD syntheses and points
to the need for a new generalizable theoretical picture for the mechanism of QD
formation and growth.
PMID- 26437712
TI - Long-term immunogenicity and safety after a single dose of the quadrivalent
meningococcal serogroups A, C, W, and Y tetanus toxoid conjugate vaccine in
adolescents and adults: 5-year follow-up of an open, randomized trial.
AB - BACKGROUND: Long-term protection against meningococcal disease is associated with
persistence of post-vaccination antibodies at protective levels. We evaluated the
bactericidal antibody persistence and safety of the quadrivalent meningococcal
serogroups A, C, W and Y tetanus-toxoid conjugate vaccine (MenACWY-TT) and the
meningococcal polysaccharide serogroups A, C, W, and Y vaccine (MenACWY-PS) up to
5 years post-vaccination. METHODS: This phase IIb, open, randomized, controlled
study conducted in the Philippines and Saudi Arabia consisted of a vaccination
phase and a long-term persistence phase. Healthy adolescents and adults aged 11
55 years were randomized (3:1) to receive a single dose of MenACWY-TT (ACWY-TT
group) or MenACWY-PS (Men-PS group). Primary and persistence results up to 3
years post-vaccination have been previously reported. Antibody responses against
meningococcal serogroups A, C, W, and Y were assessed by a serum bactericidal
antibody assay using rabbit complement (rSBA, cut-off titers 1:8 and 1:128) at
Year 4 and Year 5 post-vaccination. Vaccine-related serious adverse events (SAEs)
and cases of meningococcal disease were assessed up to Year 5. RESULTS: Of the
500 vaccinated participants, 404 returned for the Year 5 study visit (Total
Cohort Year 5). For the Total Cohort Year 5, 71.6-90.0 and 64.9-86.3 % of MenACWY
TT recipients had rSBA titers >=1:8 and >=1:128, respectively, compared to 24.8
74.3 and 21.0-68.6 % of MenACWY-PS recipients. The rSBA geometric mean titers
(GMTs) remained above the pre-vaccination levels in both treatment groups.
Exploratory analyses suggested that both rSBA GMTs as well as the percentages of
participants with rSBA titers above the cut-offs were higher in the ACWY-TT than
in the Men-PS group for serogroups A, W and Y, with no apparent difference for
MenC. No SAEs related to vaccination or cases of meningococcal disease were
reported up to Year 5. CONCLUSION: These results suggest that a single dose of
MenACWY-TT could protect at least 72 % of vaccinated adolescents and adults
against meningococcal disease at least 5 years post-vaccination. TRIAL
REGISTRATION: ClinicalTrials.gov NCT00356369.
PMID- 26437713
TI - Protocol for a systematic review of the impact of resuscitation fluids on the
microcirculation after haemorrhagic shock in animal models.
AB - BACKGROUND: Modern resuscitation strategies following haemorrhagic shock are
influenced by global haemodynamic parameters such as blood pressure and cardiac
output. Microcirculatory dysfunction in this context may persist even after
restoration of satisfactory global parameters. Additional monitoring of the
microcirculatory function may therefore be warranted in order to facilitate goal
directed therapy at a tissue oxygenation level. Although such a phenomenon is
recognised in the case of sepsis, clinical evidence regarding the behaviour of
the microcirculation following the delivery of resuscitation fluids after
haemorrhagic shock is sparse. A summation of the current state of pre-clinical
evidence is justified in order to direct avenues for future clinical research.
METHODS/DESIGN: Systematic review methodology will be utilised in order to
identify relevant studies, assess for bias, and extract data for analysis.
Medical databases will be searched to find pre-clinical studies that monitor the
microcirculatory function following haemorrhagic shock and subsequent fluid
resuscitation. Different fluid types (e.g. blood products, crystalloid, and
colloid fluids) will be compared. The search strategy will combine terms for the
animal model, resuscitation fluid, and microcirculatory parameters. Randomised
and non-randomised experiments, as well as case series, will be eligible for
inclusion. Specific quality assessment tools for pre-clinical research will be
used depending on study design. A combination of narrative and meta-analysis
techniques will be used for the synthesis of data. DISCUSSION: The choice of
type, sequence, and quantity of resuscitation fluid following haemorrhagic shock
is controversial, and the optimal strategy for restoration of microcirculatory
function is yet unknown. A detailed examination of pre-clinical data regarding
the microcirculation is timely and will enable a focussed approach to clinical
research for the improvement of resuscitation following haemorrhagic shock.
SYSTEMATIC REVIEW REGISTRATION: Collaborative Approach to Meta Analysis and
Review of Animal Data from Experimental Studies ( CAMARADES).
PMID- 26437714
TI - Interlog protein network: an evolutionary benchmark of protein interaction
networks for the evaluation of clustering algorithms.
AB - BACKGROUND: In the field of network science, exploring principal and crucial
modules or communities is critical in the deduction of relationships and
organization of complex networks. This approach expands an arena, and thus allows
further study of biological functions in the field of network biology. As the
clustering algorithms that are currently employed in finding modules have innate
uncertainties, external and internal validations are necessary. METHODS: Sequence
and network structure alignment, has been used to define the Interlog Protein
Network (IPN). This network is an evolutionarily conserved network with communal
nodes and less false-positive links. In the current study, the IPN is employed as
an evolution-based benchmark in the validation of the module finding methods. The
clustering results of five algorithms; Markov Clustering (MCL), Restricted
Neighborhood Search Clustering (RNSC), Cartographic Representation (CR),
Laplacian Dynamics (LD) and Genetic Algorithm; to find communities in Protein
Protein Interaction networks (GAPPI) are assessed by IPN in four distinct Protein
Protein Interaction Networks (PPINs). RESULTS: The MCL shows a more accurate
algorithm based on this evolutionary benchmarking approach. Also, the biological
relevance of proteins in the IPN modules generated by MCL is compatible with
biological standard databases such as Gene Ontology, KEGG and Reactome.
CONCLUSION: In this study, the IPN shows its potential for validation of
clustering algorithms due to its biological logic and straightforward
implementation.
PMID- 26437715
TI - Intranasal administration of poly-gamma glutamate induced antiviral activity and
protective immune responses against H1N1 influenza A virus infection.
AB - BACKGROUND: The global outbreak of a novel swine-origin strain of the 2009 H1N1
influenza A virus and the sudden, worldwide increase in oseltamivir-resistant
H1N1 influenza A viruses highlight the urgent need for novel antiviral therapy.
METHODS: Here, we investigated the antiviral efficacy of poly-gamma glutamate
(gamma-PGA), a safe and edible biomaterial that is naturally synthesized by
Bacillus subtilis, against A/Puerto Rico/8/1934 (PR8) and A/California/04/2009
(CA04) H1N1 influenza A virus infections in C57BL/6 mice. RESULTS: Intranasal
administration of gamma-PGA for 5 days post-infection improved survival,
increased production of antiviral cytokines including interferon-beta (IFN-beta)
and interleukin-12 (IL-12), and enhanced activation of natural killer (NK) cells
and influenza antigen-specific cytotoxic T lymphocytes (CTL) activity.
CONCLUSIONS: These results suggest that gamma-PGA protects mice against H1N1
influenza A virus by enhancing antiviral immune responses.
PMID- 26437717
TI - 2-Aminoethanol Extraction as a Method for Purifying Sc3N@C80 and for
Differentiating Classes of Endohedral Fullerenes on the Basis of Reactivity.
AB - Extraction with 2-aminoethanol is an inexpensive method for removing empty cage
fullerenes from the soluble extract from electric-arc-generated fullerene soot
that contains endohedral metallofullerenes of the type Sc3N@C2n (n = 34, 39, 40).
Our method of separation exploits the fact that C60, C70, and other larger, empty
cage fullerenes are more susceptible to nucleophilic attack than endohedral
fullerenes and that these adducts can be readily extracted into 2-aminoethanol.
This methodology has also been employed to examine the reactivity of the mixture
of soluble endohedral fullerenes that result from doping graphite rods used in
the Kratschmer-Huffman electric-arc generator with the oxides of Y, Lu, Dy, Tb,
and Gd. For example, with Y2O3, we were able to detect by mass spectrometry
several new families of endohedral fullerenes, namely Y3C108 to Y3C126, Y3C107 to
Y3C125, Y4C128 to Y4C146, that resisted reactivity with 2-aminoethanol more than
the empty cage fullerenes and the mono- and dimetallo fullerenes. The discovery
of the family Y3C107 to Y3C125 with odd numbers of carbon atoms is remarkable,
since fullerene cages must involve even numbers of carbon atoms. The newly
discovered families of endohedral fullerenes with the composition M4C2n (M = Y,
Lu, Dy, Tb, and Gd) are unusually resistant to reaction with 2-aminoethanol.
Additionally, the individual endohedrals, Y3C112 and M3C102 (M = Lu, Dy, Tb and
Gd), were remarkably less reactive toward 2-aminoethanol.
PMID- 26437716
TI - An investigation of the added value of an ACPA multiplex assay in an early
rheumatoid arthritis setting.
AB - INTRODUCTION: Recently, arrays have become available that allow the simultaneous
analysis of several anti-citrullinated protein antibody (ACPA) reactivities using
distinct citrullinated peptides. Such assays are designed for exploratory
studies. The interpretation of positive antibody reactivities can best be made if
the diagnostic and prognostic value of a multiplex array in an early arthritis
setting is known and if the multiplex-positive patients who are negative
according to three commonly used commercial ACPA assays are characterized.
METHODS: Using Thermo Scientific's ImmunoCap ISAC (Immuno Solid-phase Allergen
Chip) system, a multiplexed array that determines reactivities to 11
citrullinated peptides, we analysed serum/plasma of 195 healthy controls and 1282
early arthritis patients from two independent cohorts: the Leiden Early Arthritis
Clinic (n = 1013) and the IMPROVED (n = 269) cohort. Findings were compared with
results primarily of the anti-citrullinated cyclic peptide 2 (anti-CCP-2) assay
but also with anti- CCP-3 and anti-mutated citrullinated vimentin (anti-MCV)
assays. The associations between ACPA reactivities and patient characteristics,
risk factors (shared epitope, smoking) and disease outcomes (progression of
undifferentiated arthritis to rheumatoid arthritis (RA) and severity of joint
destruction) were assessed. RESULTS: Thirty-one percent of anti-CCP-2-negative RA
patients displayed reactivity toward citrullinated peptides in the multiplex
assay. These patients had a positive signal toward a more restricted peptide
repertoire than anti-CCP-2-positive RA patients (median of 1 versus 5). Within
anti-CCP-2-negative patients, ACPA reactivity as detected by multiplex array was
not significantly associated with known risk factors or clinical or prognostic
parameters. The frequency of sera from anti-CCP-2-negative RA patients who were
positive for the multiplexed peptides was comparable to the frequency in non-RA
arthritic patients (27 %). CONCLUSIONS: Additive citrulline peptide reactivities
detected by the current multiplex system did not reach significant power to be RA
specific. The presence of residual citrulline reactivities detected by this
multiplex system in arthritis patients who are negative in commercial ACPA assays
needs to be interpreted with caution.
PMID- 26437718
TI - Mitotically active cellular fibroma of the ovary: a case report and literature
review.
AB - BACKGROUND: The ovarian cellular fibrous tumor with mitotic figure >4 per 10 high
power field without moderate to severe atypia is defined as mitotically active
cellular fibroma according to the 2014 World Health Organization classification.
As this category is new and rare now, we described here a case of MACF and
reviewed the literature. CASE: We present a case of mitotically active cellular
fibroma of the ovary with 10-year history that was treated with laparoscopic
surgery. METHODS: We reviewed the relevant literature using PubMed search system
and analyzed the previous cases. RESULTS: To date, only 5 cases of mitotically
active cellular fibroma have been reported. Our patient is the first case of
mitotically active cellular fibroma of the ovary treated with laparoscopic
surgery. CONCLUSION: MACF of the ovary is a newly defined category and few cases
have been reported, while prognostic factors have also not yet been fully
characterized. Long-term clinical follow-up is necessary.
PMID- 26437719
TI - Food environment and fruit and vegetable intake in a urban population: a
multilevel analysis.
AB - BACKGROUND: Environmental, social and individual factors influence eating
patterns, which in turn affect the risk of many chronic diseases. This study
aimed to estimate associations between environmental factors and the consumption
of fruit and vegetables among adults in a Brazilian urban context. METHODS: Data
from the surveillance system for risk factors for chronic diseases (VIGITEL) of
Brazilian Ministry of Health were used. A cross-sectional telephone survey
(VIGITEL - 2008-2010) was carried out with 5826 adults in the urban area of Belo
Horizonte. Individual variables were collected. The frequency of fruit and
vegetables consumption was assessed from number of servings, weekly frequency and
an intake score was calculated. Georeferenced variables were used to characterize
the food environment. The density of healthy food outlets (stores specialized in
selling fruit and vegetables), unhealthy food outlets (bars, snack bars and food
trucks/trailers) and the neighborhood family income were investigated and
associated with fruit and vegetables intake score. Weighted multilevel linear
regression was used to evaluate the associations between the environment
variables and the fruit and vegetables intake score. RESULTS: Higher fruit and
vegetables intake scores were observed in neighborhoods with higher density of
healthy food outlets and higher income. Lower scores were observed in
neighborhood with higher density of unhealthy food outlets. These associations
were adjusted by individual variables such as gender, age, physical activity,
sugar sweetened beverages consumption, education level and smoking. DISCUSSION:
The food environment might explain some of the socioeconomic disparities with
respect to healthy food intake and health outcomes. Healthy food stores are less
common in socially disadvantaged neighborhoods, and therefore, healthy foods such
as fruits and vegetables are less available or are of a lower quality in lower
income areas. CONCLUSION: Food environment characteristics and neighborhood
socioeconomic level had significant associations with fruit and vegetable intake
score. These are initial findings that require further investigation within the
middle income world populations and the role of the environment with respect to
both healthy and unhealthy food acquisition and intake.
PMID- 26437721
TI - Real men are made, not born! Incidental exposure to energy drinks may promote
men's tolerance of physical pain.
AB - The energy drink market has grown exponentially since the debut of Red Bull.
Advertising of energy drinks tends to reinforce an emphasis on masculine
identification. However, no previous study has addressed the symbolic effect of
energy drinks on pain tolerance, that is, a particular masculine characteristic.
We conducted a priming-based experiment to show that energy drink primes elevated
men's pain tolerance. Induced conformity to masculinity norms mediated the
priming effect of energy drinks on pain tolerance. These findings suggest that
mere reminders of masculinity-related products can lead men to behave accordingly
in seemingly irrelevant domains (i.e., pain tolerance). Besides distraction and
placebo treatment, the connection between a symbolic masculinity prime and
greater tolerance of pain may shed lights on an alternative route for pain
control.
PMID- 26437720
TI - Effect and cost of an after-school dance programme on the physical activity of 11
12 year old girls: The Bristol Girls Dance Project, a school-based cluster
randomised controlled trial.
AB - BACKGROUND: The aim of this study was to examine the effectiveness and cost of an
after-school dance intervention at increasing the physical activity levels of
Year 7 girls (age 11-12). METHODS: A cluster randomised controlled trial was
conducted in 18 secondary schools. Participants were Year 7 girls attending a
study school. The Bristol Girls Dance Project (BGDP) intervention consisted of up
to forty, 75-minute dance sessions delivered in the period immediately after
school by experienced dance instructors over 20-weeks. The pre-specified primary
outcome was accelerometer assessed mean minutes of weekday moderate to vigorous
physical activity (MVPA) at time 2 (52 weeks are T0 baseline assessments).
Secondary outcomes included accelerometer assessed mean minutes of weekday MVPA
at time 1 (while the intervention was still running) and psychosocial outcomes.
Intervention costs were assessed. RESULTS: 571 girls participated. Valid
accelerometer data were collected from 549 girls at baseline with 508 girls
providing valid accelerometer data at baseline and time 2. There were no
differences between the intervention and control group for accelerometer assessed
physical activity at either time 1 or time 2. Only one third of the girls in the
intervention arm met the pre-set adherence criteria of attending two thirds of
the dance sessions that were available to them. Instrumental variable regression
analyses using complier average causal effects provided no evidence of a
difference between girls who attended the sessions and the control group. The
average cost of the intervention was L73 per girl, which was reduced to L63 when
dance instructor travel expenses were excluded. CONCLUSION: This trial showed no
evidence that an after-school dance programme can increase the physical activity
of Year 7 girls. The trial highlighted the difficulty encountered in maintaining
attendance in physical activity programmes delivered in secondary schools. There
is a need to find new ways to help adolescent girls to be physically active via
identifying ways to support and encourage sustained engagement in physical
activity over the life course. TRIAL REGISTRATION: ISRCTN52882523.
PMID- 26437722
TI - Cancers in Australia in 2010 attributable to modifiable factors: introduction and
overview.
AB - OBJECTIVE: To describe the approach underpinning a national project to estimate
the numbers and proportions of cancers occurring in Australia in 2010 that are
attributable to modifiable causal factors. METHODS: We estimated the population
attributable fraction (PAF) (or prevented fraction) of cancers associated with
exposure to causal (or preventive) factors using standard formulae. Where
possible, we also estimated the potential impact on cancer incidence resulting
from changes in prevalence of exposure. Analyses were restricted to factors
declared causal by international agencies: tobacco smoke; alcohol; solar
radiation; infectious agents; obesity; insufficient physical activity;
insufficient intakes of fruits, vegetables and fibre; red and processed meat;
menopausal hormone therapy (MHT); oral contraceptive pill (OCP); and insufficient
breast feeding. Separately, we estimated numbers of cancers prevented by:
aspirin; sunscreen; MHT; and OCP use. We discuss assumptions pertaining to latent
periods between exposure and cancer onset, choices of prevalence data and risk
estimates, and approaches to sensitivity analyses. RESULTS: Numbers and
population attributable fractions of cancer are presented in accompanying papers.
CONCLUSIONS: This is the first systematic assessment of population attributable
fractions of cancer in Australia.
PMID- 26437723
TI - Cancers in Australia in 2010 attributable to the consumption of alcohol.
AB - OBJECTIVE: To estimate the proportion and numbers of cancers occurring in
Australia in 2010 that are attributable to alcohol consumption. METHODS: We
estimated the population attributable fraction (PAF) of cancers causally
associated with alcohol consumption using standard formulae incorporating
prevalence of alcohol consumption and relative risks associated with consumption
and cancer. We also estimated the proportion change in cancer incidence
(potential impact fraction [PIF]) that might have occurred under the hypothetical
scenario that an intervention reduced alcohol consumption, so that no-one drank
>2 drinks/day. RESULTS: An estimated 3,208 cancers (2.8% of all cancers)
occurring in Australian adults in 2010 could be attributed to alcohol
consumption. The greatest numbers were for cancers of the colon (868) and female
breast cancer (830). The highest PAFs were for squamous cell carcinomas of the
oral cavity/pharynx (31%) and oesophagus (25%). The incidence of alcohol
associated cancer types could have been reduced by 1,442 cases (4.3%)--from
33,537 to 32,083--if no Australian adult consumed >2 drinks/day. CONCLUSIONS:
More than 3,000 cancers were attributable to alcohol consumption and thus were
potentially preventable. IMPLICATIONS: Strategies that limit alcohol consumption
to guideline levels could prevent a large number of cancers in Australian adults.
PMID- 26437724
TI - Cancers prevented in Australia in 2010 through the consumption of aspirin.
AB - OBJECTIVES: To estimate the proportion and number of cancers in Australia in 2010
that may have been prevented from occurring due to daily use of aspirin in the
population. METHODS: We calculated the Prevented Fraction (PF) of colorectal and
oesophageal cancers using standard formulae. The PF is the proportion of the
hypothetical total load of cancer in the population that was prevented by
exposure to aspirin. The formula incorporates estimates of the prevalence of
aspirin use in Australian adult populations, the relative risks associated with
aspirin use and cancer incidence. RESULTS: An estimated 335 colorectal cancers,
22 oesophageal adenocarcinomas and 29 oesophageal squamous cell carcinomas (SCC)
were potentially prevented due to daily aspirin use. These figures equate to
2.2%, 3.1% and 5.4% of all colorectal cancers, oesophageal adenocarcinomas and
oesophageal SCCs, respectively, that would otherwise have occurred but were
potentially avoided due to the daily use of aspirin pertaining in the Australian
population. CONCLUSIONS: At current levels of consumption, a small but measurable
reduction in cancer incidence can be attributed to daily aspirin use.
IMPLICATIONS: Assuming the benefits outweigh the harms of known gastrointestinal
toxicity and other hazards, aspirin use may be considered for some people to
prevent the development of particular gastrointestinal cancers.
PMID- 26437725
TI - Cancers in Australia in 2010 attributable to total breastfeeding durations of 12
months or less by parous women.
AB - OBJECTIVES: To estimate the proportion and number of cancers occurring in
Australia in 2010 attributable to parous women having breastfed for total
durations of <=12 months. METHODS: We estimated the population attributable
fraction (PAF) of breast cancers (the only cancer site with convincing evidence
of causal association) associated with women breastfeeding for <=12 months in
total, using standard formulae incorporating breastfeeding prevalence data,
relative risks associated with breastfeeding and cancer incidence. We also
estimated the proportion change in disease incidence (potential impact fraction
[PIF]) that might have occurred under two hypothetical scenarios of women
breastfeeding for longer durations. RESULTS: An estimated 235 (1.7%) breast
cancer cases that occurred in Australian in 2010 could be attributed to women
breastfeeding for total durations of <=12 months. Assuming a hypothetical
increase in breastfeeding, we estimated that the number of breast cancers
prevented would range from 36 to 51 (prevented fraction = 0.3% to 0.4%).
CONCLUSIONS: More than 200 breast cancers were attributable to women
breastfeeding for total durations of <=12 months. IMPLICATIONS: Policies to
increase breastfeeding duration may help prevent breast cancers in the future.
PMID- 26437726
TI - Cancers in Australia in 2010 attributable to inadequate consumption of fruit, non
starchy vegetables and dietary fibre.
AB - OBJECTIVES: To estimate the number and proportion of cancers occurring in
Australia in 2010 attributable to consumption deficits in fruit, non-starchy
vegetables and dietary fibre. METHODS: We estimated the population attributable
fraction (PAF) for cancers causally associated with inadequate intake of fruit
and non-starchy vegetables (oral cavity, pharynx, oesophageal squamous cell
carcinoma, stomach, larynx); inadequate intake of fruit (lung); and insufficient
intake of fibre (colorectum). We used standard formulae incorporating prevalence
of exposure (1995 National Nutrition Survey) and relative risks from independent
studies. RESULTS: Overall, 1,555 (1.4% of all) and 311 (0.3% of all) cancers were
attributable to inadequate intakes of fruit and non-starchy vegetables,
respectively. A further 2,609 colorectal cancers (18% of colorectal) were
attributable to insufficient fibre intake. If Australians increased their fibre
intake by eating the recommended daily intakes of fruit and vegetables, an
estimated 1,293 (8.8%) colorectal cancers could be prevented. CONCLUSIONS: One in
six colorectal cancer cases was attributable to inadequate intake of dietary
fibre and about 1,800 cancers at other sites were attributable to insufficient
fruit and non-starchy vegetable consumption. IMPLICATIONS: Increasing the
proportion of Australians who consume the recommended intake of fruit, vegetables
and fibre could prevent up to 4% of all cancers.
PMID- 26437727
TI - Cancers in Australia in 2010 attributable to the consumption of red and processed
meat.
AB - OBJECTIVES: To estimate the proportion and numbers of cancers in Australia in
2010 attributable to consuming red/processed meat. METHODS: We estimated the
population attributable fraction (PAF) for cancers causally associated with
red/processed meat consumption (colon, rectum) using standard formulae
incorporating prevalence of consumption (1995 National Nutrition Survey),
relative risks associated with consumption and cancer incidence. We also
estimated the proportion change in cancer incidence (potential impact fraction
[PIF]) that might have occurred under two hypothetical interventions whereby
Australian adults reduced their consumption of red/processed meat from prevailing
levels to <=100 g or <=65 g per day, respectively. RESULTS: An estimated 2,614
cases (18%) of colorectal cancer occurring in Australians in 2010 were
attributable to red/processed meat consumption (16% of colon cancers; 23% of
rectal cancers). We estimated that if all Australian adults had consumed <=65
g/day or <=100 g/day of red/processed meat, then the incidence of colorectal
cancer would have been 5.4% (798 cancers) or 1.4% (204 cancers) lower,
respectively. CONCLUSIONS: About one in six colorectal cancers in Australians in
2010 were attributable to red/processed meat consumption. IMPLICATIONS: Reducing
red/processed meat intake may reduce colorectal cancer incidence, but must be
balanced against nutritional benefits of modest lean meat consumption.
PMID- 26437728
TI - Cancers in Australia in 2010 attributable to and prevented by the use of
menopausal hormone therapy.
AB - OBJECTIVES: To estimate the proportion and number of cancers occurring in
Australia in 2010 attributable to menopausal hormone therapy (MHT) use. METHODS:
We estimated the population attributable fraction for cancers causally associated
with MHT (breast, endometrium, ovary), and the proportion of colorectal cancers
prevented by MHT. We used standard formulae incorporating Australian prevalence
data, relative risks of cancer associated with MHT and cancer incidence. We also
estimated potential change in cancer incidence under two hypothetical scenarios
whereby 25% fewer Australian women used MHT, or women exclusively used oestrogen
only MHT. RESULTS: An estimated 539 cancers in Australia in 2010 were
attributable to MHT: 453 breast, 67 endometrial and 19 ovarian cancers equating
to 3.4%, 3.1% and 1.6% of each cancer type, respectively. In contrast, MHT may
have prevented 52 colorectal cancers. If 25% fewer women used MHT, then 141
cancers may have been avoided. If women exclusively used oestrogen-only MHT then
240 cancers may have been avoided. CONCLUSIONS: MHT use caused more than 500
cancers in Australian women in 2010 and prevented ~50 colorectal cancers.
IMPLICATIONS: MHT use continues to cause an excess of cancers. The risks,
benefits, regimen and treatment duration should be carefully considered for each
woman before MHT is commenced.
PMID- 26437729
TI - Cancers in Australia in 2010 attributable to and prevented by the use of combined
oral contraceptives.
AB - OBJECTIVES: To estimate the proportion and number of cancers occurring in
Australia in 2010 attributable to combined oral contraceptive pill (OCP) use.
METHODS: We estimated the population attributable fraction (PAF) for cancers
causally associated with combined OCP use (breast, cervix), and the proportion of
endometrial and ovarian cancers prevented (prevented fraction [PF]). We used
standard formulae incorporating prevalence of combined OCP use in the Australian
population, relative risks of cancer associated with this exposure and cancer
incidence. RESULTS: An estimated 105 breast and 52 cervical cancers (0.7% and
6.4% of each cancer, respectively) in Australia in 2010 were attributable to
current use of combined OCP. Past combined OCP use was estimated to have
prevented 1,032 endometrial and 308 ovarian cancers in 2010, reducing the number
of cancers that would otherwise have occurred by 31% and 19%, respectively.
CONCLUSIONS: A small proportion of breast and cervical cancers is attributable to
combined OCP use; OCP use is likely to have prevented larger numbers of
endometrial and ovarian cancers. IMPLICATIONS: Women seeking contraceptive advice
should be told of potential adverse effects, but should also be told that - along
with reproductive health benefits - combined OCP use can reduce long-term risks
of ovarian and endometrial cancers.
PMID- 26437730
TI - Cancers in Australia in 2010 attributable to infectious agents.
AB - OBJECTIVES: To estimate the proportion and numbers of cancers in Australia in
2010 attributable to infectious agents. METHODS: The population attributable
fraction (PAF) and number of cancers caused by hepatitis B and C viruses (HBV,
HCV), Helicobacter pylori and human immunodeficiency virus (HIV) were calculated
using standard formulae incorporating prevalence of infection in the Australian
population, the relative risks associated with that infection and cancer
incidence. For cancers with very strong associations to the infectious agent
(Epstein-Barr virus [EBV], human papillomavirus [HPV] and HIV/Kaposi's sarcoma
herpes virus [KSHV]), calculations were based on viral prevalence in the tumour.
RESULTS: An estimated 3,421 cancers (2.9% of all cancers) in Australia in 2010
were attributable to infections. Infectious agents causing the largest numbers of
cancers were HPV (n=1,706), H. pylori (n=793) and HBV/HCV (n=518). Cancer sites
with the greatest number of cancers caused by infections were cervix (n=818),
stomach (n=694) and liver (n=483). Cancers with highest proportions attributable
to infectious agents were Kaposi's sarcoma (100%), cervix (100%), nasopharynx
(87%), anus (84%) and vagina (70%). CONCLUSIONS: Infectious agents cause more
than 3,000 cancers annually in Australia. IMPLICATIONS: Opportunities for cancer
prevention through infection control are considerable, even in a 'first world'
nation like Australia.
PMID- 26437731
TI - Cancers in Australia in 2010 attributable to overweight and obesity.
AB - OBJECTIVES: To estimate the proportion and number of cancers occurring in
Australia in 2010 attributable to overweight/obesity. METHODS: We estimated the
population attributable fraction (PAF) and number of cancers causally associated
with overweight/obesity. We used standard formulae incorporating Australian
prevalence data for body mass index (BMI), relative risks associated with BMI and
cancer. We also estimated the proportion change in cancer incidence (potential
impact fraction [PIF]) that may have occurred assuming that the prevalence of
overweight/obesity had remained at 1990 levels. RESULTS: An estimated 3,917
cancer cases (3.4% of all cancers) diagnosed in 2010 were attributable to
overweight/obesity, including 1,101 colon cancers, 971 female post-menopausal
breast cancers and 595 endometrial cancers (PAFs of 10%, 8% and 26%,
respectively). Highest PAFs were observed for oesophageal adenocarcinoma (31%),
endometrial cancer (26%) and kidney cancer (19%). If the prevalence of
overweight/obesity in Australia had remained at levels prevailing in 1990, we
estimate there would have been 820 fewer cancers diagnosed in 2010 (PIF 2%).
CONCLUSIONS: Overweight/obesity causes a substantial number of cancers in
Australia. IMPLICATIONS: Public health strategies to reduce the prevalence of
overweight and obesity will reduce the incidence of cancer, particularly of the
colon, breast and endometrium.
PMID- 26437732
TI - Cancers in Australia in 2010 attributable to insufficient physical activity.
AB - OBJECTIVES: To estimate the proportion and numbers of cancers occurring in
Australia in 2010 attributable to insufficient levels of physical activity.
METHODS: We estimated the population attributable fraction (PAF) of cancers
causally associated with insufficient physical activity (colon, post-menopausal
breast and endometrium) using standard formulae incorporating prevalence of
insufficient physical activity (<60 minutes at least 5 days/week), relative risks
associated with physical activity and cancer incidence. We also estimated the
proportion change in cancer incidence (potential impact fraction [PIF]) that may
have occurred assuming that everyone with insufficient activity levels increased
their exercise by 30 minutes/week. RESULTS: An estimated 1,814 cases of colon,
post-menopausal breast and endometrial cancer were attributable to insufficient
levels of physical activity: 707 (6.5%) colon; 971 (7.8%) post-menopausal breast;
and 136 (6.0%) endometrial cancers. If those exercising below the recommended
level had increased their activity level by 30 minutes/week, we estimate 314
fewer cancers (17% of those attributable to insufficient physical activity) would
have occurred in 2010. CONCLUSIONS: More than 1,500 cancers were attributable to
insufficient levels of physical activity in the Australian population.
IMPLICATIONS: Increasing the proportion of Australians who exercise could reduce
the incidence of several common cancers.
PMID- 26437733
TI - Cancers in Australia in 2010 attributable to tobacco smoke.
AB - OBJECTIVES: To estimate the population attributable fraction (PAF) and numbers of
cancers occurring in Australia in 2010 attributable to tobacco smoking, both
personal and by a partner. METHODS: We used a modified Peto-Lopez approach to
calculate the difference between the number of lung cancer cases observed and the
number expected assuming the entire population developed lung cancer at the same
rate as never smokers. For cancers other than lung, we applied the standard PAF
formula using relative risks from a large cohort and derived notional smoking
prevalence. To estimate the PAF for partners' smoking, we used the standard
formula incorporating the proportion of non-smoking Australians living with an
ever-smoking partner and relative risks associated with partner smoking. RESULTS:
An estimated 15,525 (13%) cancers in Australia in 2010 were attributable to
tobacco smoke, including 8,324 (81%) lung, 1,973 (59%) oral cavity and pharynx,
855 (60%) oesophagus and 951 (6%) colorectal cancers. Of these, 136 lung cancers
in non-smokers were attributable to partner tobacco smoke. CONCLUSIONS: More than
one in eight cancers in Australia is attributable to tobacco smoking and would be
avoided if nobody smoked. IMPLICATIONS: Strategies to reduce the prevalence of
smoking remain a high priority for cancer control.
PMID- 26437734
TI - Cancers in Australia attributable to exposure to solar ultraviolet radiation and
prevented by regular sunscreen use.
AB - OBJECTIVES: To estimate the proportion and numbers of cancers occurring in
Australia attributable to solar ultraviolet radiation (UVR) and the proportion
and numbers prevented by regular sun protection factor (SPF) 15+ sunscreen use.
METHODS: We estimated the population attributable fraction (PAF) and numbers of
melanomas and keratinocyte cancers (i.e. basal cell carcinomas and squamous cell
carcinomas) due to exposure to ambient UVR resulting from residing in Australia
versus residing in the UK (for melanoma) or Scandinavia (for keratinocyte
cancers). We also estimated the prevented fraction (PF): the proportion of
cancers that would have occurred but were likely prevented by regular sunscreen
use. RESULTS: An estimated 7,220 melanomas (PAF 63%) and essentially all
keratinocyte cancers occurring in Australia were attributable to high ambient UVR
levels in Australia. We estimated that regular sunscreen use prevented around
14,190 (PF 9.3%) and 1,730 (PF 14%) people from developing SCC and melanoma,
respectively. CONCLUSIONS: Although our approach was conservative, a high
proportion of skin cancers in Australia are attributable to high ambient levels
of UVR. Prevailing levels of sunscreen use probably reduced skin cancer incidence
by 10-15%. IMPLICATIONS: Most skin cancers are preventable. Sunscreen should be a
component of a comprehensive sun protection strategy.
PMID- 26437736
TI - Addendum.
AB - Swinburn B, Moore M. Urgently needed: voices for integrity in public policy
making. Aust NZ J Public Health 2014;38:505.It has been brought to our attention
that following the publication of this Editorial, the Office of the Auditor
General investigated and found no conflict of interest between Katherine Rich's
role as a member of the board of the Health Promotion Agency and her role as
chief executive of the New Zealand Food & Grocery Council.
PMID- 26437737
TI - New GP contract will replace targets with seven day working.
PMID- 26437735
TI - Cancers in Australia in 2010 attributable to modifiable factors: summary and
conclusions.
AB - OBJECTIVE: To estimate the numbers and proportions of cancers occurring in
Australia in 2010 attributable to modifiable causal factors. METHODS: We
estimated the population attributable fraction (PAF) of cancers associated with
exposure to 13 causal factors using standard formulae incorporating exposure
prevalence and relative risk data. We also calculated the potential impact of
changing exposure to some factors. RESULTS: A total of 32% of all cancers
diagnosed in Australia in 2010 (excluding keratinocyte cancers) were attributable
to the 13 factors assessed (men 33%; women 31%). Leading factors were tobacco
smoke (PAF all cancers: 13.4%), solar radiation (6.2%), inadequate diet (6.1%)
and overweight/obesity (3.4%). Factors conferring highest PAFs differed by sex:
highest PAFs for men were tobacco smoke (15.8%), solar radiation (7.1%) and
alcohol (3.0%); while highest PAFs for women were tobacco smoke (10.1%), solar
radiation (5.0%) and overweight/obesity (4.5%). Sites with the highest counts of
potentially preventable cancers were lung (8,569), colorectal (7,404), melanoma
of the skin (7,220) and breast (3,233). CONCLUSIONS: At least one in three
cancers in Australia is attributable to exposure to known modifiable factors.
IMPLICATIONS: Up to 37,000 cancers could be prevented in Australia each year if
the population avoided exposure to 13 common factors known or strongly suspected
to cause cancer.
PMID- 26437738
TI - Rational design of nanomaterials for water treatment.
AB - The ever-increasing human demand for safe and clean water is gradually pushing
conventional water treatment technologies to their limits. It is now a popular
perception that the solutions to the existing and future water challenges will
hinge upon further developments in nanomaterial sciences. The concept of rational
design emphasizes on 'design-for-purpose' and it necessitates a scientifically
clear problem definition to initiate the nanomaterial design. The field of
rational design of nanomaterials for water treatment has experienced a
significant growth in the past decade and is poised to make its contribution in
creating advanced next-generation water treatment technologies in the years to
come. Within the water treatment context, this review offers a comprehensive and
in-depth overview of the latest progress in rational design, synthesis and
applications of nanomaterials in adsorption, chemical oxidation and reduction
reactions, membrane-based separation, oil-water separation, and synergistic
multifunctional all-in-one nanomaterials/nanodevices. Special attention is paid
to the chemical concepts related to nanomaterial design throughout the review.
PMID- 26437739
TI - Deep Learning for Drug-Induced Liver Injury.
AB - Drug-induced liver injury (DILI) has been the single most frequent cause of
safety-related drug marketing withdrawals for the past 50 years. Recently, deep
learning (DL) has been successfully applied in many fields due to its exceptional
and automatic learning ability. In this study, DILI prediction models were
developed using DL architectures, and the best model trained on 475 drugs
predicted an external validation set of 198 drugs with an accuracy of 86.9%,
sensitivity of 82.5%, specificity of 92.9%, and area under the curve of 0.955,
which is better than the performance of previously described DILI prediction
models. Furthermore, with deep analysis, we also identified important molecular
features that are related to DILI. Such DL models could improve the prediction of
DILI risk in humans. The DL DILI prediction models are freely available at
http://www.repharma.cn/DILIserver/DILI_home.php.
PMID- 26437740
TI - A study on the association between serum amyloid A and sperm concentration.
AB - Our aim was to compare peripheral blood and seminal fluid serum amyloid A (SAA)
protein levels in men classified on the basis of sperm concentration and
investigate whether SAA protein is an important marker of male infertility. A
total of 74 first-attempt IVF male partners of infertile couples classified as
azoospermic (n = 25), oligozoospermic (n = 25) and normozoospermic group (n = 24)
were recruited for this cross-sectional study. There was no difference with
respect to age, BMI, infertility period and smoking ratio. No difference in
haematologic parameters including white blood cell count, neutrophil ratio,
lymphocyte ratio, neutrophil-to-lymphocyte ratio and blood SAA level was found
between the groups. Seminal fluid SAA level was 17.85 +/- 2.21 ng ml(-1) in
azoospermics, 16.13 +/- 3.58 ng ml(-1) in oligozoospermics and 15.67 +/- 4.77 ng
ml(-1) in normozoospermics, showing no significant difference. Seminal SAA level
was found to be not correlated with blood SAA levels. Therefore, we could not
find any associations between these parameters at all. However, further studies
with more participants are needed to address the exact action of SAA on
spermatogenesis.
PMID- 26437741
TI - Assessment of gene expression levels of proopiomelanocortin (POMC) and
melanocortin-1 receptor (MC1R) in vitiligo.
AB - Proopiomelanocortin (POMC) and melanocortin 1 receptor (MC1R) are regulators of
melanogenesis and pigmentation. Our objective was to estimate their levels,
searching for a possible role of the melanocortin system in vitiligo. This study
included 40 vitiligo patients and 40 controls. Skin biopsies were taken from
lesional and non-lesional skin of patients and from the non-sun exposed skin of
controls to detect the expression of POMC and MC1R using quantitative real-time
polymerase chain reaction. Both factors were significantly lower in lesional than
non-lesional skin and controls, while they were significantly higher in non
lesional skin than in controls. There was a statistically significant positive
correlation between lesional levels of POMC and MC1R, as well as between non
lesional levels of POMC and MC1R in the patients. On the other hand, we found a
statistically significant negative correlation between the lesional and non
lesional levels of POMC, as well as between the lesional and non-lesional levels
of MC1R in the patients. As a conclusion, the melanocortin system could play a
role in the pathogenesis of vitiligo or could be affected as the end result of
the disease.
PMID- 26437742
TI - Diagnosing appendicitis: What works, what does not and where to go from here?
AB - Although acute appendicitis is the most common reason for emergency abdominal
surgery in children, diagnosis is far from straightforward. Delays in diagnosis
can result in significant complications, whereas over-diagnosis can result in
costly inter-hospital transfers and unnecessary surgery. This article aims to
describe current evidence-based assessment of children with possible appendicitis
presenting to the emergency department. We provide an overview of the literature
relating to the various available diagnostic approaches, including the
application of history, examination, pathology tests, imaging, and clinical
decision rules.
PMID- 26437743
TI - CSL regulates AKT to mediate androgen independence in prostate cancer
progression.
AB - BACKGROUND: Aberrant signaling pathways leads to cancer initiation and
progression. Both Notch and PI3K/AKT signaling pathways are believed to be
involved in prostate cancer. How the interaction between the two pathways
contributes to prostate cancer progression to androgen independence is still
elusive. METHODS: Prostate cancer cells were grown in RPMI 1,640 supplemented
with 10% heat-inactivated fetal bovine serum (FBS) or 10% charcoal-stripped heat
inactivated fetal bovine serum (FCS), 1% penicillin-streptomycin in 75 cm2
polystyrene flasks, and maintained at 37 degrees C in a humidified atmosphere
with 5% CO2 . Cell proliferation, invasion were performed with cell counting,
matrigel assay in vitro. Dual luciferase assays were performed using reporter
plasmids with ARE (Androgen Response Element, ARE). RNA interference was applied
to gene silence. Tumorigenicity of cancer cells was evaluated by mouse xenograft
in vivo. RESULTS: A subpopulation of casodex resistant prostate cancer cells were
identified with an overexpressed androgen receptor (AR) and aggressive
phenotypes, characterized with high proliferation, invasion in vitro and enhanced
tumorigenesis in vivo. Gene profiling for androgen-dependent LNCaP and androgen
independent LNCaP-CR revealed that both CSL and AKT gave the similar expressional
pattern upon casodex treatment. Immunoblot demonstrated that CSL and AKT were
dramatically suppressed in androgen dependent LNCaP cells, but slightly inhibited
in LNCaP-CR cells as well as other androgen independent prostate cancer cells.
Further studies indicated that CSL regulates AKT, and subsequently AR in prostate
cancer cells. AKT mediates casodex resistance and androgen independence through
regulation of cyclin D1. CONCLUSION: CSL-AKT-AR axis might play an important role
in prostate cancer progression. Targeting CSL depleted the casodex resistant
population through inhibition of the AKT, suggesting a more effective therapeutic
strategy for abrogating casodex resistance in advanced prostate cancer.
PMID- 26437744
TI - Regiocomplementary O-Methylation of Catechols by Using Three-Enzyme Cascades.
AB - S-Adenosylmethionine (SAM)-dependent enzymes have great potential for selective
alkylation processes. In this study we investigated the regiocomplementary O
methylation of catechols. Enzymatic methylation is often hampered by the need for
a stoichiometric supply of SAM and the inhibitory effect of the SAM-derived
byproduct on most methyltransferases. To counteract these issues we set up an
enzyme cascade. Firstly, SAM was generated from l-methionine and ATP by use of an
archaeal methionine adenosyltransferase. Secondly, 4-O-methylation of the
substrates dopamine and dihydrocaffeic acid was achieved by use of SafC from the
saframycin biosynthesis pathway in 40-70 % yield and high selectivity. The
regiocomplementary 3-O-methylation was catalysed by catechol O-methyltransferase
from rat. Thirdly, the beneficial influence of a nucleosidase on the overall
conversion was demonstrated. The results of this study are important milestones
on the pathway to catalytic SAM-dependent alkylation processes.
PMID- 26437746
TI - The role of size polydispersity in magnetic fluid hyperthermia: average vs. local
infra/over-heating effects.
AB - An efficient and safe hyperthermia cancer treatment requires the accurate control
of the heating performance of magnetic nanoparticles, which is directly related
to their size. However, in any particle system the existence of some size
polydispersity is experimentally unavoidable, which results in a different local
heating output and consequently a different hyperthermia performance depending on
the size of each particle. With the aim to shed some light on this significant
issue, we have used a Monte Carlo technique to study the role of size
polydispersity in heat dissipation at both the local (single particle) and global
(macroscopic average) levels. We have systematically varied size polydispersity,
temperature and interparticle dipolar interaction conditions, and evaluated local
heating as a function of these parameters. Our results provide a simple guide on
how to choose, for a given polydispersity degree, the more adequate average
particle size so that the local variation in the released heat is kept within
some limits that correspond to safety boundaries for the average-system
hyperthermia performance. All together we believe that our results may help in
the design of more effective magnetic hyperthermia applications.
PMID- 26437745
TI - Thrombocytopenia and Cornelia de Lange syndrome: Still an enigma?
AB - Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder caused by mutations
in the cohesion complex and its regulators. The syndrome is characterized by
multiple organ system abnormalities, pre- and post-natal growth retardation and
typical facial features. Thrombocytopenia is a reduction in platelet count to
<150 * 10(9) L. It can be caused by congenital or acquired decreased production,
increased destruction, or sequestration of platelets. In recent years, several
papers reported thrombocytopenia and immune thrombocytopenia in patients affected
by CdLS. In 2011, Lambert et al. estimated the risk of idiopathic
thrombocytopenia purpura in CdLS patients to be 31-633 times greater than in the
general population. We describe the incidence of thrombocytopenia in 127 Italian
CdLS patients, identifying patients with transient or persistent
thrombocytopenia, but a lower incidence of true idiopathic thrombocytopenic
purpura (ITP).
PMID- 26437747
TI - Molecular Catalyst Immobilized Photocathodes for Water/Proton and Carbon Dioxide
Reduction.
AB - As one of the components in a tandem photoelectrochemical cell for solar-fuel
production, the photocathode carries out the reduction reaction to convert solar
light and the corresponding substrate (e.g., proton and CO2) into target fuels.
Immobilizing molecular catalysts onto the photocathode is a promising strategy to
enhance the interfacial electron/hole-transfer process and to improve the
stability of the catalysts. Furthermore, the molecular catalysts are beneficial
in improving the selectivity of the reduction reaction, particularly for CO2
reduction. On the photocathode, the binding mode of the catalysts and the
arrangement between the photosensitizer and the catalyst also play crucial roles
in the performance and stability of the final device. How to firmly and
effectively immobilize the catalyst on the photoelectrode is now becoming a
scientific question. Recent publications on molecular catalyst immobilized
photocathodes are therefore surveyed.
PMID- 26437748
TI - Stereospecific Pd-Catalyzed Intermolecular C(sp(3))-C(sp) Cross-Coupling of
Diarylmethyl Carbonates and Terminal Alkynes Under Base-Free Conditions.
AB - A palladium-catalyzed intermolecular decarboxylative C(sp(3))-C(sp) coupling of
diarylmethyl carbonates and terminal alkynes has been developed. The reaction
proceeds smoothly under external base-free conditions to deliver the
corresponding alkynylated diarylmethanes with the liberation of CO2 and MeOH as
the sole byproducts. Moreover, enantioenriched diarylmethyl carbonates are
stereospecifically converted to optically active cross-coupling products with
inversion of configuration. Thus, the stereospecific palladium catalysis can
provide new and unique access to the alkynylated chiral tertiary stereocenters,
which are relatively difficult to construct by conventional methods.
PMID- 26437749
TI - Laboratory tests for disorders of complement and complement regulatory proteins.
AB - The complement pathway is a cascade of proteases that is involved in immune
surveillance and innate immunity, as well as adaptive immunity. Dysfunction of
the complement cascade may be mediated by aberrations in the pathways of
activation, complement regulatory proteins, or complement deficiencies, and has
been linked to a number of hematologic disorders, including paroxysmal noctural
hemoglobinuria (PNH), hereditary angioedema (HAE), and atypical hemolytic-uremic
syndrome (aHUS). Here, current laboratory tests for disorders of the complement
pathway are reviewed, and their utility and limitations in hematologic disorders
and systemic diseases are discussed. Current therapeutic advances targeting the
complement pathway in treatment of complement-mediated hematologic disorders are
also reviewed.
PMID- 26437750
TI - Consideration surrounding incidental findings throughout multigene panel testing
in cancer genetics.
PMID- 26437751
TI - Reactivity differences of Sc3N@C(2n) (2n = 68 and 80). Synthesis of the first
methanofullerene derivatives of Sc3N@D(5h)-C80.
AB - Using a purification method introduced earlier based on redox properties it was
possible to isolate Sc3N@I(h)-C80 and Sc3N@D(3h)-C78 and a mixture of Sc3N@D(5h)
C80 and Sc3N@D3-C68. Taking advantage of their chemical reactivity differences,
Sc3N@D(5h)-C80 was isolated from Sc3N@D3-C68 followed by further
functionalization, giving rise to five new methano-derivatives of Sc3N@D(5h)-C80.
PMID- 26437752
TI - [Noma/Cancrum oris: a neglected disease].
AB - Noma is an aggressive orofacial gangrenous pathology that damages hard and soft
tissues of the mouth and the face. Throughout the centuries it has been present
around the globe, but nowadays it has practically disappeared from developed
countries and mainly affects children from the most disadvantaged places,
especially in Africa. Noma disease is a multifactorial process; malnutrition,
debilitating diseases (bacterial or viral systemic diseases, HIV-associated
immunosuppression, etc.) and intraoral infections are some of the factors
implied. The characteristic tissue necrosis is produced by a polymicrobial
infection. Fusobacterium necrophorum, Prevotella intermedia, Prevotella
melaninogenica, Fusobacterium nucleatum, Bacteroides fragilis, Bacillus cereus,
Trueperella pyogenes, spyrochetes, etc, are some of the species that have been
isolated from the affected areas. Without treatment, noma is lethal in a short
period of time, and the patients that survive show severe sequelae that hinder
their life and interpersonal relationships. The aim of this paper is to unify the
existing information and to promote wider knowledge and awareness among the
population.
PMID- 26437753
TI - [Boosted protease inhibitor monotherapy in HIV-infected patients: results of a
study in a real life setting].
AB - BACKGROUND: Boosted protease inhibitor monotherapy may offer antiviral efficacy
while reducing drug interactions, costs and toxicity. The aim of this study was
to assess the efficacy of darunavir/ritonavir (DRV/r) and lopinavir/ritonavir
(LPV/r) monotherapy in a real life setting. METHODS: A retrospective analysis of
all HIV infected patients, who had initiated DRV/r or LPV/r monotherapy, was
performed. Patients whose HIV viral load had remained undetectable for at least
two consecutive follow-up visits and who had no neurocognitive disorder or
hepatitis B co-infection, were included. RESULTS: Sixty patients were included.
The median (IQR) time to follow-up was 66 (33-118) weeks. The proportions (CI95%)
of patients with virological failure were 6.3% (1.7- 20.2) and 25.0% (12.7-43.4),
respectively, in the DRV/r and LPV/r groups (p= 0.0424). The proportions (CI95%)
of patients with therapeutic success were 90.6% (80.5-100) in the DRV/r group and
60.7% (42.6-78.8) in the LPV/r group (p=0.0063). No protease inhibitor mutations
were detected. During the follow-up, 6 patients with dyslipidemia normalized
their lipid values. The median monthly cost was 410 (IQR 242-416) euros per
person lower for the monotherapy than for the combined antiretroviral therapy.
CONCLUSIONS: Boosted protease inhibitor monotherapy was effective in a real life
setting. This study showed differences in favour of DRV/r as compared with LPV/r
in terms of therapeutic success; however prospective studies are needed to
confirm these results. Finally, although this study was not specifically designed
to detect benefits in terms of costs and lipid profile, it shows evidence of a
positive impact of monotherapy in these fields.
PMID- 26437754
TI - Vitek MS matrix-assisted laser desorption ionization-time of flight mass
spectrometry for identifying respiratory bacterial pathogens: a fast and
efficient method.
AB - Mass spectrometry has become a reference resource for identifying microorganisms
in clinical microbiology services. One hundred and fifty one clinical isolates
were selected from respiratory specimens routinely identified as Streptococcus
pneumoniae (43), Haemophilus influenzae (64) and Moraxella catarrhalis (44).
These identifications were compared with other phenotypical methods and mass
spectrometry (MALDI-TOF-MS Vitek). Result discrepancies were assessed by 16S rRNA
sequencing. Thirty-eight of the 43 strains of S. pneumoniae (86%) were identified
as such using phenotypical methods and spectrometry. In 5 cases, MALDI-TOF
identified 4 of them as Streptococcus pseudopneumoniae and 1 as S. mitis/oralis.
Forty-eight of the 64 strains were identified as H. influenzae (75%) using
biochemical identification systems and automated identification systems, whereas
MALDI-TOF-MS Vitek identified 51 strains (79%) as such. Conventional methods and
spectrometry identified all the 40 strains tested (100%) as M. catarrhalis. All
strains with discrepant results were sequenced, and in all cases, the
identification obtained by spectrometry was confirmed. The results obtained in
this study show that mass spectrometry provides identification of these bacteria
faster and in a more reliable way than those based on conventional phenotypical
methods.
PMID- 26437755
TI - A two-hour procedure for determining the susceptibility of enterococci and
staphylococci to antibiotics by a colourimetric method.
AB - INTRODUCTION: Rapid determination of the antibiotic susceptibility test in
bacteria remains a challenge for Clinical Microbiology laboratories. METHODS: An
improvement in the colorimetric antimicrobial susceptibility testing performed
with resazurin in enterococci and staphylococci has been carried out. The design
of method was performed using two collection strains, which have a known
susceptibility. This procedure was then validated against standard commercial
methods on 15 strains of staphylococci and 15 strains of enterococci from
patients. RESULTS: The essential agreement between the colorimetric method and
commercial methods (E-test, MicroScan and VITEK2) was 100%. CONCLUSION: Resazurin
allows us to obtain a reliable antibiotic susceptibility test in staphylococci
and enterococci in less than two hours.
PMID- 26437756
TI - [Bacteraemia due to extended-spectrum beta-lactamases (ESBL) and other beta
lactamases (ampC and carbapenemase) producing Enterobacteriaceae: association
with health-care and cancer].
AB - INTRODUCTION: Bloodstream infections due to multire-sistant Enterobacteriaceae
are a major matter of concern nowadays. The present study evaluated the impact of
these infections in our area. METHODS: Prospective observational study of a
cohort of patients with bacteraemia due to extended-spectrum beta-lactamases
(ESBL) and other beta-lactamases producing organisms among hospitalized patients
in Cruces Hospital for 2 years. We conducted a descriptive analysis, a subgroup
analysis (cancer vs. non-cancer patients) and a mortality analysis. RESULTS:
During the study period, 3409 episodes of bacteraemia were diagnosed, of which
124 (3.6%) were ESBL and other beta-lactamases producing Enterobacteriaceae.
40.3% of the cases were nosocomial, 15.3% community acquired and 44.4% were
health-care associated. 44.4% of the cohort had cancer as underlying disease. The
most commonly isolated organism was E. coli (83% of cases), regardless of the
source of infection. 58.1% of patients received inadequate empirical therapy. 7
day-mortality was 10.5% and 30 day-mortality was 21.8%. None of the analyzed
variables showed association with 7 and 14 day-mortality, but the presence of
solid cancer (p= 0.032) and advanced HIV infection (p = 0.027), were
significantly associated with higher 30 day-mortality. CONCLUSIONS: More than
half of bacteraemia episodes affected outpatients and most of them were health
care associated episodes. Even though more than half of the patients received
inadequate empirical treatment, this was not related to higher mortality. We only
found an association between 30 day-mortality and the presence of underlying
solid malignancy or advanced HIV infection.
PMID- 26437757
TI - [Evaluation of antibiotic resistance of Escherichia coli in urinary tract
infections in Primary Care Barbastro Sector (Huesca)].
AB - OBJECTIVES: Evaluate the resistance of community-uropathogen, Escherichia coli to
several antibiotics in our health sector and deduce empirical treatment options.
METHODS: E. coli strains isolated from urine cultures of patients from Primary
Care Barbastro Sector, between January 2011 and December 2013, were studied. The
resistances rates for nine common antibiotics were determined, and differences in
sensitivity were analyzed, comparing confidence intervals for proportions by the
method of Wilson. RESULTS: E. coli was the most frequently isolated bacteria
(61.08% of positive urine cultures sent from Primary Care). Overall, there has
been an increase in resistance of E. coli isolates in all antimicrobials studied.
Still, resistance has remained below 4% compared to fosfomycin and nitrofurantoin
and below 10% in cephalosporins second and third generation. Resistance to
amoxicillin-clavulanate has increased progressively reaching 21.5% in 2013; only
this antibiotic has presented a statistically significant increase. The maximum
levels of resistance (over 30%) were found in the antibiotics administered orally
and often indicated in uncomplicated urinary tract infections: trimethoprim
sulfamethoxazole, ciprofloxacin and ampicillin. CONCLUSIONS: Update knowledge
susceptibility patterns of microorganisms most commonly isolated in urine samples
in each health area allows to choose the most suitable and effective treatments
trough empirical knowledge.
PMID- 26437758
TI - [Carotid mycotic pseudoaneurysm. Case report and review].
PMID- 26437759
TI - [Bacteraemia by Staphylococcus aureus from respiratory origin and mortality].
PMID- 26437760
TI - [Yersinia pseudotuberculosis septicemia. Case report].
PMID- 26437762
TI - Consensus statement: patient safety, healthcare-associated infections and
hospital environmental surfaces.
AB - Healthcare-associated infections have serious implications for both patients and
hospitals. Environmental surface contamination is the key to transmission of
nosocomial pathogens. Routine manual cleaning and disinfection eliminates visible
soil and reduces environmental bioburden and risk of transmission, but may not
address some surface contamination. Automated area decontamination technologies
achieve more consistent and pervasive disinfection than manual methods, but it is
challenging to demonstrate their efficacy within a randomized trial of the
multiple interventions required to reduce healthcare-associated infection rates.
Until data from multicenter observational studies are available, automated area
decontamination technologies should be an adjunct to manual cleaning and
disinfection within a total, multi-layered system and risk-based approach
designed to control environmental pathogens and promote patient safety.
PMID- 26437763
TI - Yield Point of Semiconducting Polymer Films on Stretchable Substrates Determined
by Onset of Buckling.
AB - Mechanical buckling of thin films on elastomeric substrates is often used to
determine the mechanical properties of polymers whose scarcity precludes
obtaining a stress-strain curve. Although the modulus and crack-onset strain can
readily be obtained by such film-on-elastomer systems, information critical to
the development of flexible, stretchable, and mechanically robust electronics
(i.e., the range of strains over which the material exhibits elastic behavior)
cannot be measured easily. This paper describes a new technique called laser
determination of yield point (LADYP), in which a polymer film on an elastic
substrate is subjected to cycles of tensile strain that incrementally increase in
steps of 1% (i.e., 0% -> 1% -> 0% -> 2% -> 0% -> 3% -> 0%, etc.). The formation
of buckles manifests as a diffraction pattern obtained using a laser, and
represents the onset of plastic deformation, or the yield point of the polymer.
In the series of conjugated polymers poly(3-alkylthiophene), where the alkyl
chain is pentyl, hexyl, heptyl, octyl, and dodecyl, the yield point is found to
increase with increasing length of the side chain (from approximately 5% to 15%
over this range when holding the thickness between ~200 and 300 nm). A skin-depth
effect is observed in which films of <150 nm thickness exhibit substantially
greater yield points, up to 40% for poly(3-dodecylthiophene). Along with the
tensile modulus obtained by the conventional analysis of the buckling
instability, knowledge of the yield point allows one to calculate the modulus of
resilience. Combined with knowledge of the crack-onset strain, one can estimate
the total energy absorbed by the film (i.e., the modulus of toughness).
PMID- 26437761
TI - Sodium nitrate alleviates functional muscle ischaemia in patients with Becker
muscular dystrophy.
AB - Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease
for which there is no treatment. BMD is caused by in-frame mutations in the gene
encoding dystrophin, a structural cytoskeletal protein that also targets other
proteins to the sarcolemma. Among these is neuronal nitric oxide synthase mu
(nNOSMU), which requires specific spectrin-like repeats (SR16/17) in dystrophin's
rod domain and the adaptor protein alpha-syntrophin for sarcolemmal targeting.
When healthy skeletal muscle is exercised, sarcolemmal nNOSMU-derived nitric
oxide (NO) attenuates alpha-adrenergic vasoconstriction, thus optimizing
perfusion. In the mdx mouse model of dystrophinopathy, this protective mechanism
(functional sympatholysis) is defective, resulting in functional muscle
ischaemia. Treatment with a NO-donating non-steroidal anti-inflammatory drug
(NSAID) alleviates this ischaemia and improves the murine dystrophic phenotype.
In the present study, we report that, in 13 men with BMD, sympatholysis is
defective mainly in patients whose mutations disrupt sarcolemmal targeting of
nNOSMU, with the vasoconstrictor response measured as a decrease in muscle
oxygenation (near infrared spectroscopy) to reflex sympathetic activation. Then,
in a single-arm, open-label trial in 11 BMD patients and a double-blind, placebo
controlled cross-over trial in six patients, we show that acute treatment with
oral sodium nitrate, an inorganic NO donor without a NSIAD moiety, restores
sympatholysis and improves post-exercise hyperaemia (Doppler ultrasound). By
contrast, sodium nitrate improves neither sympatholysis, nor hyperaemia in
healthy controls. Thus, a simple NO donor recapitulates the vasoregulatory
actions of sarcolemmal nNOS in BMD patients, and constitutes a putative novel
therapy for this disease.
PMID- 26437764
TI - Diverting Hydrogenations with Wilkinson's Catalyst towards Highly Reactive
Rhodium(I) Species.
AB - The addition of Barton's base has a dramatic effect on the classic rhodium(III)
mediated hydrogenations promoted by Wilkinson's catalyst. Following the initial
oxidative addition, a barrierless reductive elimination of HCl from the
traditional rhodium(III) intermediates instantly produces a rhodium(I)
monohydride species, which is remarkably reactive in the hydrogenation of several
internal alkynes and functionalized trisubstituted alkenes. The direct formation
of this species is unprecedented upon addition of molecular hydrogen and its
catalytic potential has been hitherto barely explored.
PMID- 26437766
TI - SCExV: a webtool for the analysis and visualisation of single cell qRT-PCR data.
AB - BACKGROUND: Single cell gene expression assays have become a powerful tool with
which to dissect heterogeneous populations. While methods and software exist to
interrogate such data, what has been lacking is a unified solution combining
analysis and visualisation which is also accessible and intuitive for use by non
bioinformaticians, as well as bioinformaticians. RESULTS: We present the Single
cell expression visualiser (SCExV), a webtool developed to expedite the analysis
of single cell qRT-PCR data. SCExV is able to take any data matrix of Ct values
as an input, but can handle files exported by the Fluidigm Biomark platform
directly. In addition, SCExV also accepts and automatically integrates cell
surface marker intensity values which are measured during index sorting. This
allows the user to directly visualise relationships between a single cell gene
expression profile and the immunophenotype of the interrogated cell. CONCLUSIONS:
SCExV is a freely available webtool created to import, filter, analyse, and
visualise single cell gene expression data whilst being able to simultaneously
consider cellular immunophenotype. SCExV is designed to be intuitive to use
whilst maintaining advanced functionality and flexibility in how analyses are
performed.
PMID- 26437765
TI - Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene
expression and circulating levels in healthy adults.
AB - BACKGROUND: Vascular endothelial growth factor (VEGF) plays a key role in
angiogenesis. The aim was to assess the genetic connections between the
angiogenesis-related NOS3, CD14, MMP3, IL4R, IL4 genes and VEGF expression and
plasma levels. METHODS: The associations between VEGF plasma levels with the
polymorphisms of NOS3, CD14, MMP3, IL4R, and IL4 were assessed in 403 healthy
unrelated adults. The epistatic and environmental interactions were explored,
including four VEGF-related polymorphisms previously identified. The VEGF
expression in peripheral blood mononuclear cells was quantified (n = 65) for the
VEGF121, VEGF145, VEGF165, and VEGF189 isoforms. RESULTS: The polymorphism
rs1799983 of NOS3 was associated with the sum of all VEGF isoforms mRNA levels (P
= 0.032) and VEGF145 (P = 0.033). Rs1800779 of NOS3 interacted with rs3918226 of
the same gene and with the rs2569190 of CD14 (P = 0.022, P = 0.042, respectively)
for VEGF plasma levels. Other epistatic interactions included the rs1801275 of
IL4R with the rs6921438 (VEGF-related variant) and rs3025058 of MMP3 (P = 0.042,
P = 0.010 respectively) and the rs2569190 of CD14 with the rs3025058 of MMP3 (P =
0.0119). We also identified an interaction of rs1800779 with obesity, high
density lipoprotein cholesterol and triglycerides (P = 0.018, P = 0.005, P =
0.043, respectively) as well as the interaction of rs6921438 with hypertension (P
= 0.028). CONCLUSIONS: Our findings indicated that genetic variants of NOS3,
CD14, MMP3 and IL4R are implicated in the determination of VEGF expression and
plasma levels. Thus, they support the hypothesis that in physiological conditions
there are complex biological relationships between pathways (such as angiogenesis
and inflammation), which are involved in the development of chronic diseases.
PMID- 26437767
TI - Epilepsy is a possible feature in Williams-Beuren syndrome patients harboring
typical deletions of the 7q11.23 critical region.
AB - Seizures are rarely reported in Williams-Beuren syndrome (WBS)--a contiguous-gene
deletion disorder caused by a 7q11.23 heterozygous deletion of 1.5-1.8 Mb--and no
previous study evaluated electro-clinical features of epilepsy in this syndrome.
Furthermore, it has been hypothesized that atypical deletion (e.g., larger than
1.8 Mb) may be responsible for a more pronounced neurological phenotypes,
especially including seizures. Our objectives are to describe the electro
clinical features in WBS and to correlate the epileptic phenotype with deletion
of the 7q11.23 critical region. We evaluate the electro-clinical features in one
case of distal 7q11.23 deletion syndrome and in eight epileptic WBS (eWBS)
patients. Additionally, we compare the deletion size-and deleted genes-of four
epileptic WBS (eWBS) with that of four non-epileptic WBS (neWBS) patients.
Infantile spasms, focal (e.g., motor and dyscognitive with autonomic features)
and generalized (e.g., tonic-clonic, tonic, clonic, myoclonic) seizures were
encountered. Drug-resistance was observed in one patient. Neuroimaging discovered
one case of focal cortical dysplasia, one case of fronto-temporal cortical
atrophy and one case of periventricular nodular heterotopia. Comparison of
deletion size between eWBS and neWBS patients did not reveal candidate genes
potentially underlying epilepsy. This is the largest series describing electro
clinical features of epilepsy in WBS. In WBS, epilepsy should be considered both
in case of typical and atypical deletions, which do not involve HIP1, YWHAG or
MAGI2.
PMID- 26437768
TI - Drosophila innate immunity: regional and functional specialization of
prophenoloxidases.
AB - BACKGROUND: The diversification of immune systems during evolution involves the
expansion of particular gene families in given phyla. A better understanding of
the metazoan immune system requires an analysis of the logic underlying such
immune gene amplification. This analysis is now within reach due to the ease with
which we can generate multiple mutations in an organism. In this paper, we
analyze the contribution of the three Drosophila prophenoloxidases (PPOs) to host
defense by generating single, double and triple mutants. PPOs are enzymes that
catalyze the production of melanin at the site of infection and around parasites.
They are the rate-limiting enzymes that contribute to the melanization reaction,
a major immune mechanism of arthropods. The number of PPO-encoding genes is
variable among insects, ranging from one in the bee to ten in the mosquito.
RESULTS: By analyzing mutations alone and in combination, we ascribe a specific
function to each of the three PPOs of Drosophila. Our study confirms that two
PPOs produced by crystal cells, PPO1 and PPO2, contribute to the bulk of
melanization in the hemolymph, upon septic or clean injury. In contrast, PPO3, a
PPO restricted to the D. melanogaster group, is expressed in lamellocytes and
contributes to melanization during the encapsulation process. Interestingly,
another overlapping set of PPOs, PPO2 and PPO3, achieve melanization of the
capsule upon parasitoid wasp infection. CONCLUSIONS: The use of single or
combined mutations allowed us to show that each PPO mutant has a specific
phenotype, and that knocking out two of three genes is required to abolish fully
a particular function. Thus, Drosophila PPOs have partially overlapping functions
to optimize melanization in at least two conditions: following injury or during
encapsulation. Since PPO3 is restricted to the D. melanogaster group, this
suggests that production of PPO by lamellocytes emerged as a recent defense
mechanism against parasitoid wasps. We conclude that differences in spatial
localization, immediate or late availability, and mode of activation underlie the
functional diversification of the three Drosophila PPOs, with each of them having
non-redundant but overlapping functions.
PMID- 26437769
TI - Pore-formation by adenylate cyclase toxoid activates dendritic cells to prime
CD8+ and CD4+ T cells.
AB - The adenylate cyclase toxin-hemolysin (CyaA) of Bordetella pertussis is a bi
functional leukotoxin. It penetrates myeloid phagocytes expressing the complement
receptor 3 and delivers into their cytosol its N-terminal adenylate cyclase
enzyme domain (~400 residues). In parallel, ~1300 residue-long RTX hemolysin
moiety of CyaA forms cation-selective pores and permeabilizes target cell
membrane for efflux of cytosolic potassium ions. The non-enzymatic CyaA-AC(-)
toxoid, has repeatedly been successfully exploited as an antigen delivery tool
for stimulation of adaptive T-cell immune responses. We show that the pore
forming activity confers on the CyaA-AC(-) toxoid a capacity to trigger Toll-like
receptor and inflammasome signaling-independent maturation of CD11b-expressing
dendritic cells (DC). The DC maturation-inducing potency of mutant toxoid
variants in vitro reflected their specifically enhanced or reduced pore-forming
activity and K(+) efflux. The toxoid-induced in vitro phenotypic maturation of DC
involved the activity of mitogen activated protein kinases p38 and JNK and
comprised increased expression of maturation markers, interleukin 6, chemokines
KC and LIX and granulocyte-colony-stimulating factor secretion, prostaglandin E2
production and enhancement of chemotactic migration of DC. Moreover, i.v.
injected toxoids induced maturation of splenic DC in function of their cell
permeabilizing capacity. Similarly, the capacity of DC to stimulate CD8(+) and
CD4(+) T-cell responses in vitro and in vivo was dependent on the pore-forming
activity of CyaA-AC(-). This reveals a novel self-adjuvanting capacity of the
CyaA-AC(-) toxoid that is currently under clinical evaluation as a tool for
delivery of immunotherapeutic anti-cancer CD8(+) T-cell vaccines into DC.
PMID- 26437770
TI - mTORC1 signaling is crucial for regulatory T cells to suppress macrophage
mediated inflammatory response after acute myocardial infarction.
AB - Post-infarction inflammatory response results in worse remodeling and dysfunction
following myocardial infarction (MI). Supression of post-infarction inflammation
would be a logical approach of alleviating post-infarction injury and promoting
cardiac repair. In this study, we investigated the significance of mTORC1
signaling in the anti-inflammatory activity of regulatory T cells (Tregs) after
MI. Using the murine MI model with wild type and Rag1(-/-) mice, we found that
the mechanistic target of rapamycin compex 1 (mTORC1) signaling was upregulated
in Tregs infiltrating into the infarcted myocardium, rather than in circulating
Tregs after MI. The anti-inflammatory activity of infiltrating Tregs was
significantly stronger than that of circulating Tregs. This was demonstrated by a
higher expression of anti-inflammatory cytokines in the infiltrating Tregs and a
robust suppression of proinflammatory cytokine production by macrophages. In an
adoptive transfer analysis, compared with normal splenic Tregs, rapamycin-treated
splenic Tregs ineffectively suppressed the post-infarction inflammatory response
of infiltrating macrophages. In addition, in vitro cultured primary
cardiomyocytes treated with mild oxygen glucose deprivation induced mTORC1
activation and a higher anti-inflammatory activity of Tregs in a coculture assay.
Our study identified a new mechanism by which infiltrating Tregs subdue post
infarction inflammation. Understanding and utilizing this information would be
helpful for designing new therapeutic interventions for MI.
PMID- 26437771
TI - Functional development of the adult ovine mammary gland--insights from gene
expression profiling.
AB - BACKGROUND: The mammary gland is a dynamic organ that undergoes dramatic
physiological adaptations during the transition from late pregnancy to lactation.
Investigation of the molecular basis of mammary development and function will
provide fundamental insights into tissue remodelling as well as a better
understanding of milk production and mammary disease. This is important to
livestock production systems and human health. Here we use RNA-seq to identify
differences in gene expression in the ovine mammary gland between late pregnancy
and lactation. RESULTS: Between late pregnancy (135 days of gestation +/- 2.4 SD)
and lactation (15 days post partum +/- 1.27 SD) 13 % of genes in the sheep genome
were differentially expressed in the ovine mammary gland. In late pregnancy, cell
proliferation, beta-oxidation of fatty acids and translation were identified as
key biological processes. During lactation, high levels of milk fat synthesis
were mirrored by enrichment of genes associated with fatty acid biosynthesis,
transport and lipogenesis. Protein processing in the endoplasmic reticulum was
enriched during lactation, likely in support of active milk protein synthesis.
Hormone and growth factor signalling and activation of signal transduction
pathways, including the JAK-STAT and PPAR pathways, were also differently
regulated, indicating key roles for these pathways in functional development of
the ovine mammary gland. Changes in the expression of epigenetic regulators,
particularly chromatin remodellers, indicate a possible role in coordinating the
large-scale transcriptional changes that appear to be required to switch mammary
processes from growth and development during late pregnancy to synthesis and
secretion of milk during lactation. CONCLUSIONS: Coordinated transcriptional
regulation of large numbers of genes is required to switch between mammary tissue
establishment during late pregnancy, and activation and maintenance of milk
production during lactation. Our findings indicate the remarkable plasticity of
the mammary gland, and the coordinated regulation of multiple genes and pathways
to begin milk production. Genes and pathways identified by the present study may
be important for managing milk production and mammary development, and may inform
studies of diseases affecting the mammary gland.
PMID- 26437772
TI - New users of antipsychotic medication: A population-based cohort study of
occupational outcome measures in relation to antipsychotic on-label and off-label
prescribing practices.
AB - BACKGROUND: Treatment with antipsychotic medication is thoroughly investigated in
schizophrenia and bipolar disorder but is also widely applied for a diversity of
off-label conditions, despite an uncertain risk-benefit ratio. This study
examined the relationship between antipsychotic prescribing patterns and labor
market affiliation, considering both authority approved and off-label
prescriptions and the relation to polypharmacy. METHODS: Register-based cohort
study using a dataset of 71,254 new antipsychotic users with a psychiatric
diagnosis. Labor market affiliation and duration of welfare payments were
analyzed using linear regression models and duration analysis. The analyses were
adjusted for the following confounding variables: age, gender, diagnosis, marital
status, length of education, and utilization of mental health care services.
RESULTS: The majority of new antipsychotic users received welfare payments for
prolonged periods of time during the observation period, even more so for
individuals treated with antipsychotic polypharmacy or other antipsychotic
combination regimens. The risk of permanently leaving the labor market was also
associated with antipsychotic combination regimen. CONCLUSIONS: Antipsychotic
treatment, especially in combination with other antipsychotics or other
psychotropic drugs, could serve as a marker of subjects with increased need for
support to maintain the labor market affiliation. However, causality cannot be
inferred from an observational study because of residual confounding that could
not be adjusted for in this study.
PMID- 26437773
TI - Archaeal ancestors of eukaryotes: not so elusive any more.
AB - The origin of eukaryotes is one of the hardest problems in evolutionary biology
and sometimes raises the ominous specter of irreducible complexity.
Reconstruction of the gene repertoire of the last eukaryotic common ancestor
(LECA) has revealed a highly complex organism with a variety of advanced features
but no detectable evolutionary intermediates to explain their origin. Recently,
however, genome analysis of diverse archaea led to the discovery of apparent
ancestral versions of several signature eukaryotic systems, such as the actin
cytoskeleton and the ubiquitin network, that are scattered among archaea. These
findings inspired the hypothesis that the archaeal ancestor of eukaryotes was an
unusually complex form with an elaborate intracellular organization. The latest
striking discovery made by deep metagenomic sequencing vindicates this hypothesis
by showing that in phylogenetic trees eukaryotes fall within a newly identified
archaeal group, the Lokiarchaeota, which combine several eukaryotic signatures
previously identified in different archaea. The discovery of complex archaea that
are the closest living relatives of eukaryotes is most compatible with the
symbiogenetic scenario for eukaryogenesis.
PMID- 26437774
TI - The effect of local variation in malaria transmission on the prevalence of
sulfadoxine-pyrimethamine resistant haplotypes and selective sweep
characteristics in Malawi.
AB - BACKGROUND: Persistence of sulfadoxine-pyrimethamine (SP) resistance has been
described in an urban setting in Malawi where malaria transmission is relatively
low. Higher malaria transmission is associated with greater genetic diversity and
more frequent genetic recombination, which could lead to a more rapid re
emergence of SP-sensitive parasites, as well as more rapid degradation of
selective sweeps. In this study, the impact of local variation in malaria
transmission on the prevalence of SP-resistant haplotypes and selective sweep
characteristics was investigated at an urban site with low parasite prevalence
and two rural sites with moderate and high parasite prevalence. METHODS: Samples
from three sites with different parasite prevalence were genotyped for resistance
markers within pfdhfr-ts and pfdhps and at microsatellites flanking these genes.
Expected heterozygosity (He) was estimated to evaluate genetic diversity.
RESULTS: No difference in the prevalence of highly resistant DHFR 51I/59R/108N
and DHPS 437G/540E was found between sites. Small differences in He flanking
pfdhfr-ts and pfdhps were seen between rural-moderate and the other sites, as
well as some shared haplotypes between the rural-high and urban-low sites.
CONCLUSIONS: The results do not show an effect of local variation in malaria
transmission, as inferred from parasite prevalence, on SP-resistant haplotype
prevalence.
PMID- 26437775
TI - Identification of H2S3 and H2S produced by 3-mercaptopyruvate sulfurtransferase
in the brain.
AB - Hydrogen polysulfides (H2Sn) have a higher number of sulfane sulfur atoms than
hydrogen sulfide (H2S), which has various physiological roles. We recently found
H2Sn in the brain. H2Sn induced some responses previously attributed to H2S but
with much greater potency than H2S. However, the number of sulfur atoms in H2Sn
and its producing enzyme were unknown. Here, we detected H2S3 and H2S, which were
produced from 3-mercaptopyruvate (3 MP) by 3-mercaptopyruvate sulfurtransferase
(3MST), in the brain. High performance liquid chromatography with fluorescence
detection (LC-FL) and tandem mass spectrometry (LC-MS/MS) analyses showed that
H2S3 and H2S were produced from 3 MP in the brain cells of wild-type mice but not
3MST knockout (3MST-KO) mice. Purified recombinant 3MST and lysates of COS cells
expressing 3MST produced H2S3 from 3 MP, while those expressing defective 3MST
mutants did not. H2S3 was localized in the cytosol of cells. H2S3 was also
produced from H2S by 3MST and rhodanese. H2S2 was identified as a minor H2Sn, and
3 MP did not affect the H2S5 level. The present study provides new insights into
the physiology of H2S3 and H2S, as well as novel therapeutic targets for diseases
in which these molecules are involved.
PMID- 26437776
TI - A functional polymorphism in the CEBPE gene promoter influences acute
lymphoblastic leukemia risk through interaction with the hematopoietic
transcription factor Ikaros.
PMID- 26437778
TI - Retraction: The onset of thalamic hemorrhage in Rivaroxaban in oral IX factor
complex formulation administration, but showed a hematoma expansion case.
AB - This article released online on July 11, 2015 as advance publication was
retracted by author's request.
PMID- 26437777
TI - A simple one-tube assay for immunophenotypical quantification of leukemic stem
cells in acute myeloid leukemia.
AB - Relapses after initial successful treatment in acute myeloid leukemia are thought
to originate from the outgrowth of leukemic stem cells. Their flow cytometrically
assessed frequency is of importance for relapse prediction and is therefore
assumed to be implemented in future risk group profiling. Since current detection
methods are complex, time- and bone marrow consuming (multiple-tubes approach),
it would be advantageous to have a broadly applicable approach that enables to
quantify leukemia stem cells both at diagnosis and follow-up. We compared 15
markers in 131 patients concerning their prevalence, usefulness and stability in
CD34(+)CD38(-) leukemic stem cell detection in healthy controls, acute myeloid
leukemia diagnosis and follow-up samples. Ultimately, we designed a single 8
color detection tube including common markers CD45, CD34 and CD38, and specific
markers CD45RA, CD123, CD33, CD44 and a marker cocktail (CLL-1/TIM
3/CD7/CD11b/CD22/CD56) in one fluorescence channel. Validation analyses in 31
patients showed that the single tube approach was as good as the multiple-tube
approach. Our approach requires the least possible amounts of bone marrow, and is
suitable for multi-institutional studies. Moreover, it enables detection of
leukemic stem cells both at time of diagnosis and follow-up, thereby including
initially low-frequency populations emerging under therapy pressure.
PMID- 26437779
TI - Serum levels of inflammatory cytokines in Rift Valley fever patients are
indicative of severe disease.
AB - BACKGROUND: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis affecting
domestic and wild ruminants, camels and humans. Outbreaks of RVF are
characterized by a sudden onset of abortions and high mortality amongst domestic
ruminants. Humans develop disease ranging from a mild flu-like illness to more
severe complications including hemorrhagic syndrome, ocular and neurological
lesions and death. During the RVF outbreak in South Africa in 2010/11, a total of
278 human cases were laboratory confirmed, including 25 deaths. The role of the
host inflammatory response to RVF pathogenesis is not completely understood.
METHODS: Virus load in serum from human fatal and non-fatal cases was determined
by standard tissue culture infective dose 50 (TCID50) titration on Vero cells.
Patient serum concentration of chemokines and cytokines involved in inflammatory
responses (IL-8, RANTES, CXCL9, MCP-1, IP-10, IL-1beta, IL-6, IL-10, TNF and IL
12p70) was determined using cytometric bead assays and flow cytometry. RESULTS:
Fatal cases had a 1-log10 higher TCID50/ml serum concentration of RVF virus
(RVFV) than survivors (p < 0.05). There were no significant sequence differences
between isolates recovered from fatal and non-fatal cases. Chemokines and pro-
and anti-inflammatory cytokines were detected at significantly increased (IL-8,
CXCL9, MCP-1, IP-10, IL-10) or decreased (RANTES) levels when comparing fatal
cases to infected survivors and uninfected controls, or when comparing combined
infected patients to uninfected controls. CONCLUSIONS: The results suggest that
regulation of the host inflammatory responses plays an important role in the
outcome of RVFV infection in humans. Dysregulation of the inflammatory response
contributes to a fatal outcome. The cytokines and chemokines identified in this
study that correlate with fatal outcomes warrant further investigation as markers
for disease severity.
PMID- 26437780
TI - PLD1 participates in BDNF-induced signalling in cortical neurons.
AB - The brain-derived neurotrophic factor BDNF plays a critical role in neuronal
development and the induction of L-LTP at glutamatergic synapses in several brain
regions. However, the cellular and molecular mechanisms underlying these BDNF
effects have not been firmly established. Using in vitro cultures of cortical
neurons from knockout mice for Pld1 and Rsk2, BDNF was observed to induce a rapid
RSK2-dependent activation of PLD and to stimulate BDNF ERK1/2-CREB and mTor-S6K
signalling pathways, but these effects were greatly reduced in Pld1(-/-) neurons.
Furthermore, phospho-CREB did not accumulate in the nucleus, whereas
overexpression of PLD1 amplified the BDNF-dependent nuclear recruitment of
phospho-ERK1/2 and phospho-CREB. This BDNF retrograde signalling was prevented in
cells silenced for the scaffolding protein PEA15, a protein which complexes with
PLD1, ERK1/2, and RSK2 after BDNF treatment. Finally PLD1, ERK1/2, and RSK2
partially colocalized on endosomal structures, suggesting that these proteins are
part of the molecular module responsible for BDNF signalling in cortical neurons.
PMID- 26437783
TI - Paroxysmal nocturnal hemoglobinuria induced by the occurrence of BCR-ABL in a
PIGA mutant hematopoietic progenitor cell.
PMID- 26437782
TI - Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase:
results from the European ENEST1st study.
AB - The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line
Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic
myeloid leukemia in chronic phase. The rate of deep molecular response (MR(4)
(BCR-ABL1?0.01% on the International Scale or undetectable BCR-ABL1 with ?10,000
ABL1 transcripts)) at 18 months was evaluated as the primary end point, with
molecular responses monitored by the European Treatment and Outcome Study network
of standardized laboratories. This analysis was conducted after all patients had
completed 24 months of study treatment (80.9% of patients) or discontinued early.
In patients with typical BCR-ABL1 transcripts and ?3 months of prior imatinib
therapy, 38.4% (404/1052) achieved MR(4) at 18 months. Six patients (0.6%)
developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of
nilotinib was consistent with that of previous studies, although the frequencies
of some nilotinib-associated adverse events were lower (for example, rash,
21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine
monitoring of lipid and glucose levels was not mandated in the protocol. These
results support the use of frontline nilotinib, particularly when achievement of
a deep molecular response (a prerequisite for attempting treatment-free remission
in clinical trials) is a treatment goal.
PMID- 26437784
TI - Prospective molecular monitoring of minimal residual disease after non
myeloablative allografting in newly diagnosed multiple myeloma.
PMID- 26437781
TI - A20 targets caspase-8 and FADD to protect HTLV-I-infected cells.
AB - Adult T-cell leukemia (ATL) arises from a human T-cell leukemia virus type I
(HTLV-I)-infected cell and has few therapeutic options. Here, we have uncovered a
previously unrecognized role for a ubiquitin-editing enzyme A20 in the survival
of HTLV-I-infected cells. Unlike in lymphomas of the B-cell lineage, A20 is
abundantly expressed in primary ATL cells without notable mutations. Depletion of
A20 in HTLV-I-infected cells resulted in caspase activation, cell death induction
and impaired tumorigenicity in mouse xenograft models. Mechanistically, A20
stably interacts with caspase-8 and Fas-associated via death domain (FADD) in
HTLV-I-infected cells. Mutational studies revealed that A20 supports the growth
of HTLV-I-infected cells independent of its catalytic functions and that the zinc
finger domains are required for the interaction with and regulation of caspases.
These results indicate a pivotal role for A20 in the survival of HTLV-I-infected
cells and implicate A20 as a potential therapeutic target in ATL.
PMID- 26437785
TI - Oncogenic activation of MPL/thrombopoietin receptor by 17 mutations at W515:
implications for myeloproliferative neoplasms.
PMID- 26437786
TI - Profiling serum antibodies to Mycobacterium tuberculosis proteins in rhesus
monkeys with nontuberculous Mycobacteria.
AB - Recent evidence indicates that the prevalence of diseases caused by
nontuberculous mycobacteria (NTM) has been increasing in both human and animals.
In this study, antibody profiles of NTM in rhesus monkeys (Macaca mulatta) were
determined and compared with those of monkeys infected with Mycobacterium
tuberculosis complex (MTBC). Antibodies against 10 M. tuberculosis proteins,
purified protein derivative (PPD), and mammalian old tuberculin (MOT) were
detected in 14 monkeys naturally infected with NTM by indirect ELISA. Sera from
10 monkeys infected with MTBC and 10 healthy monkeys were set as controls. All
antigens showed high serological reactivities to MTBC infections and low
reactivities in healthy monkeys. NTM infections showed strong antibody responses
to MOT and PPD; moderate antibody responses to 16kDa, U1, MPT64L, 14kDa, and
TB16.3; and low antibody responses to 38kDa, Ag85b, CFP10, ESAT-6, and CFP10-ESAT
6. According to the criteria of MTBC, only CFP10, ESAT-6, and CFP10-ESAT-6 showed
negative antibody responses in all NTM infections. Taken together, these results
suggest that positive results of a PPD/MOT-based ELISA in combination with
results of antibodies to M. tuberculosis-specific antigens, such as CFP10 and
ESAT-6, could discriminate NTM and MTBC infections. Two positive results indicate
an MTBC infection, and a negative result for an M. tuberculosis-specific antigen
may preliminarily predict an NTM infection.
PMID- 26437787
TI - Construction and evaluation of the novel DNA vaccine harboring the inhibin alpha
(1-32) and the RF-amide related peptide-3 genes for improving fertility in mice.
AB - To further improve fertility of animals, a novel gene RFRP-3 (RF-amide related
peptide-3, RFRP-3) was used to construct DNA vaccines with INH alpha (1-32)
(inhibin, INH) fragment for the first time. The aim of this study was to evaluate
the effects of novel DNA vaccines on fertility in mice. Synthesized SINH and
SRFRP (INH and RFRP genes were separately ligated to the C-terminus of the small
envelope protein of the hepatitis B virus (HBV-S) gene) fragments were inserted
into multiple cloning site of pIRES vector to develop p-SINH/SRFRP. The
synthesized tissue plasminogen activator (TPA) signal sequence was then inserted
into the p-SINH/SRFRP to construct p-TPA-SINH/TPA-SFRFP. Meanwhile, p-SINH was
prepared and considered as positive control. Forty Kunming mice were equally
divided into four groups and respectively immunized by electroporation with p
SINH, p-SINH/SRFRP and p-TPA-SINH/TPA-SRFRP vaccine (three times at 2 weeks
interval) and saline as control. Results showed that the average antibodies (P/N
value) of anti-INH and anti-RFRP in mice inoculated with p-TPA-SINH/TPA-SFRFP
were significantly higher (P<0.05) than those inoculated with p-SINH/SRFRP and
the positive rates were 100% (anti-INH) and 90% (anti-RFRP) respectively, at 2
weeks after the third immunization. Litter size of mice immunized with the three
recombinant plasmids was higher (P<0.05) than that of the control, and litter
size of mice immunized with p-TPA-SINH/TPA-SRFRP significantly increased (P<0.05)
compared with p-SINH. These results suggested that the p-TPA-SINH/TPA-SRFRP
harboring INH and RFRP genes was successfully constructed and had good
immunogenicity, and might effectively increase litter size.
PMID- 26437788
TI - What's happening to cheap generic drugs?
PMID- 26437789
TI - CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death
inducing proteins.
AB - The CCR4-NOT complex is conserved in eukaryotes and is involved in mRNA
metabolism, though its molecular physiological roles remain to be established. We
show here that CNOT3-depleted mouse embryonic fibroblasts (MEFs) undergo cell
death. Levels of other complex subunits are decreased in CNOT3-depleted MEFs. The
death phenotype is rescued by introduction of wild-type (WT), but not mutated
CNOT3, and is not suppressed by the pan-caspase inhibitor, zVAD
fluoromethylketone. Gene expression profiling reveals that mRNAs encoding cell
death-related proteins, including receptor-interacting protein kinase 1 (RIPK1)
and RIPK3, are stabilized in CNOT3-depleted MEFs. Some of these mRNAs bind to
CNOT3, and in the absence of CNOT3 their poly(A) tails are elongated. Inhibition
of RIPK1-RIPK3 signaling by a short-hairpin RNA or a necroptosis inhibitor,
necrostatin-1, confers viability upon CNOT3-depleted MEFs. Therefore, we conclude
that CNOT3 targets specific mRNAs to prevent cells from being disposed to
necroptotic death.
PMID- 26437790
TI - Correlation of single-breath count test and neck flexor muscle strength with
spirometry in myasthenia gravis.
AB - INTRODUCTION: Although formal spirometry is the gold standard for monitoring
respiratory function in patients with myasthenia gravis (MG), such testing is
often delayed or unavailable. There is a need for a simple bedside test that can
accurately measure respiratory function. METHODS: We conducted a prospective,
cross-sectional, single-blind study in adults with acetylcholine receptor
antibody positive MG. Participants performed the single breath count test (SBCT)
and underwent manual muscle strength testing, and a respiratory therapist
performed spirometry blinded to SBCT and strength results. RESULTS: Thirty-one
patients, aged 57 +/- 19 years participated. SBCT showed significant correlations
with forced vital capacity (FVC), negative inspiratory force, and neck flexor
strength (P < 0.01). FVC showed significant correlation with neck flexor strength
(P = 0.02) but no correlation with shoulder abductor strength. CONCLUSIONS: These
data suggest that the SBCT and neck flexor strength testing are valuable tools
for bedside assessment of respiratory function in MG patients.
PMID- 26437791
TI - Screening for Down syndrome in the second trimester of pregnancy.
AB - Antenatal screening for fetal anomalies has provided women and their partners
with information to make reproductive choices based on the risk of serious
chromosomal or structural defects since the 1990s. Alternative tests include
first-trimester screening (combined ultrasound and maternal serum markers),
second-trimester maternal serum markers and noninvasive cell-free DNA testing.
The recent recommendations by the Royal Australian and New Zealand College of
Obstetrics and Gynaecology and the Human Genetics Society of Australasia against
second-trimester triple testing are based on unsound performance criteria, raise
several contestable issues around access and equity and challenge the principles
of governments providing affordable options.
PMID- 26437792
TI - Safety assessment of the Clostridium butyricum MIYAIRI 588(r) probiotic strain
including evaluation of antimicrobial sensitivity and presence of Clostridium
toxin genes in vitro and teratogenicity in vivo.
AB - Probiotics are live microorganisms ingested for the purpose of conferring a
health benefit on the host. Development of new probiotics includes the need for
safety evaluations that should consider factors such as pathogenicity,
infectivity, virulence factors, toxicity, and metabolic activity. Clostridium
butyricum MIYAIRI 588((r)) (CBM 588((r))), an anaerobic spore-forming bacterium,
has been developed as a probiotic for use by humans and food animals. Safety
studies of this probiotic strain have been conducted and include assessment of
antimicrobial sensitivity, documentation of the lack of Clostridium toxin genes,
and evaluation of CBM 588((r)) on reproductive and developmental toxicity in a
rodent model. With the exception of aminoglycosides, to which anaerobes are
intrinsically resistant, CBM 588((r)) showed sensitivity to all antibiotic
classes important in human and animal therapeutics. In addition, analysis of the
CBM 588((r)) genome established the absence of genes for encoding for alpha,
beta, or epsilon toxins and botulin neurotoxins types A, B, E, or F. There were
no deleterious reproductive and developmental effects observed in mice associated
with the administration of CBM 588((r)) These data provide further support for
the safety of CBM 588((r)) for use as a probiotic in animals and humans.
PMID- 26437793
TI - Lipid emulsion attenuates apoptosis induced by a toxic dose of bupivacaine in
H9c2 rat cardiomyoblast cells.
AB - The goal of this in vitro study was to investigate the effect of lipid emulsion
on apoptosis induced by a toxic dose of bupivacaine (BPV) in H9c2 rat
cardiomyoblast cell lines. The effect of lipid emulsion on the decreased cell
viability and count induced by BPV or mepivacaine (MPV) in the H9c2 cells was
assessed using an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide
assay or a cell count assay. The effect of BPV or lipid emulsion combined with
BPV on cleaved caspase 3, caspase 8, and Bax in H9c2 cells was investigated using
Western blotting. A terminal deoxynucleotidyl transferase dUTP2'-deoxyuridine 5'
triphosphate nick end-labeling (TUNEL) assay was performed to detect apoptosis of
H9c2 cells treated with BPV alone or lipid emulsion combined with BPV. The
magnitude of lipid emulsion-mediated attenuation of decreased cell viability
induced by BPV was higher than that of lipid emulsion-mediated attenuation of
decreased cell viability induced by MPV. Lipid emulsion attenuated the increases
in cleaved caspase 3, caspase 8 and Bax induced by BPV. Lipid emulsion attenuated
the increases in TUNEL-positive cells induced by BPV. These results suggest that
lipid emulsion attenuates a toxic dose of BPV-induced apoptosis via inhibition of
the extrinsic and intrinsic apoptotic pathways. The protective effect of lipid
emulsion may be partially associated with the relatively high lipid solubility of
BPV.
PMID- 26437795
TI - An Infected Aneurysm of the Vertebral Artery Treated with a Stent-graft: A Case
Report.
AB - In a 75-year-old man, a growing vertebral artery aneurysm at the C3/4
intervertebral level was found at postoperative evaluation of cervical abscess,
which was diagnosed as a complication of sepsis subsequent to cholangitis. Even
after a successful antibiotic treatment and a surgical drainage, the aneurysm
grew enough to cause compression of esophagus and trachea. The aneurysm was
judged to be infection-related, based on the clinical course and the anatomical
vicinity to the abscess. Following a dual antiplatelet treatment (clopidogrel 75
mg and aspirin 100 mg per day) for a week, the patient underwent endovascular
treatment of the aneurysm with a stent-graft. Postoperative angiography showed
complete obliteration of the aneurysm with preserving patency of the vertebral
artery. A dual antiplatelet treatment was continued for 6 months and was changed
to a single antiplatelet treatment (clopidogrel 75 mg per day) thereafter.
Neither recurrence of the aneurysm nor stent-graft infection was observed for 4
years of follow-up. This case illustrates the potential use of a stent-graft in
the treatment of an infected aneurysm.
PMID- 26437794
TI - Proteolysis of MDA5 and IPS-1 is not required for inhibition of the type I IFN
response by poliovirus.
AB - BACKGROUND: The type I interferon (IFN) response is a critical component of the
innate immune response to infection by RNA viruses and is initiated via
recognition of viral nucleic acids by RIG-like receptors (RLR). Engagement of
these receptors in the cytoplasm initiates a signal transduction pathway leading
to activation of the transcription factors NF-kappaB, ATF-2 and IRF-3 that
coordinately upregulate transcription of type I IFN genes, such as that encoding
IFN-beta. In this study the impact of poliovirus infection on the type I
interferon response has been examined. METHODS: The type I IFN response was
assessed by measuring IFN-beta mRNA levels using qRT-PCR and normalizing to
levels of beta-actin mRNA. The status of host factors involved in activation of
the type I IFN response was examined by immunoblot, immunofluorescence microcopy
and qRT-PCR. RESULTS: The results show that poliovirus infection results in
induction of very low levels of IFN-beta mRNA despite clear activation of NF
kappaB and ATF-2. In contrast, analysis of IRF-3 revealed no transcriptional
induction of an IRF-3-responsive promoter or homodimerization of IRF-3 indicating
it is not activated in poliovirus-infected cells. Exposure of poliovirus-infected
cells to poly(I:C) results in lower levels of IFN-beta mRNA synthesis and IRF-3
activation compared to mock-infected cells. Analysis of MDA-5 and IPS-1 revealed
that these components of the RLR pathway were largely intact at times when the
type I IFN response was suppressed. CONCLUSIONS: Collectively, these results
demonstrate that poliovirus infection actively suppresses the host type I
interferon response by blocking activation of IRF-3 and suggests that this is not
mediated by cleavage of MDA-5 or IPS-1.
PMID- 26437796
TI - Retreatment of Recurrent Internal Carotid-Posterior Communicating Artery Aneurysm
after Coil Embolization.
AB - Internal carotid-posterior communicating artery (IC-PC) aneurysms account for
more than 20% of all intracranial aneurysms. As a result of the increase in
coiling, there has also been an increase in recurrent IC-PC aneurysms after
coiling. We present our experience of 10 recurrent IC-PC aneurysms after coiling
that were retreated using surgical or endovascular techniques in order to discuss
the choice of treatment and the points of clipping without removal of coils. From
2007 to 2014, 10 recurrent IC-PC aneurysms after coiling were retreated. When the
previous frames covered the aneurysms all around or almost around except a part
of the neck, coiling was chosen. In other cases, clipping was chosen. Clipping
was attempted without removal of coils when it was technically feasible. Among
the 10 IC-PC aneurysms retreated, 3 were retreated with coiling and 7 were
retreated with clipping. In all three cases retreated with coiling, almost
complete occlusion was accomplished. In the seven cases retreated with clipping,
coil extrusion was observed during surgery in six cases. In most of them, it was
necessary to dissect strong adhesions around the coiled aneurysms and to utilize
temporary occlusion of the internal carotid artery. In all seven cases, neck
clipping was accomplished without the removal of coils. There were no
neurological complications in any cases. The management of recurrent lesions of
embolized IC-PC aneurysms requires appropriate choice of treatment using both
coiling and clipping. Clipping, especially without the removal of coils, plays an
important role in safe treatment.
PMID- 26437797
TI - Toll-like Receptor 4 (TLR4) is Associated with Cerebral Vasospasm and Delayed
Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.
AB - In the present prospective study, the Toll-like receptor 4 (TLR4) levels on
peripheral blood mononuclear cells (PBMCs) were investigated in 30 patients with
aneurysmal subarachnoid hemorrhage (aSAH) and in 20 healthy controls (HCs). The
relationship between TLR4 levels and the occurrence of cerebral vasospasm (CVS)
was also analyzed. TLR4 expression level on cell surface of PBMCs on days 1, 3,
and 7 after admission was determined by flow cytometry. Results showed that
patients with aSAH presented a significantly higher TLR4 levels. For patients
with Hunt-Hess grades IV-V, higher TLR4 levels were also observed; higher TLR4
levels have already been seen in patients developing CVS and/or delayed cerebral
ischemia (DCI). Higher TLR4 levels were also associated with modified Fisher
score, occurrence of dCVS, DCI, cerebral infarction (CT), and poor neurological
functional recovery. Binary logistic regression analysis indicated that high TLR4
expression on blood monocytes was an independent predictive factor of the
occurrence of dCVS, DCI, and poor neurological functional recovery. Taken
together, TLR4 levels on PBMCs is significantly altered in the early stage of
aSAH, especially in those patients experiencing CVS and DCI. Furthermore, higher
TLR4 levels in the early stage of aSAH is also associated with the neurological
function outcome. As far as we know, this is the first clinical study about
TLR4's significance for patients with aSAH.
PMID- 26437798
TI - Distribution of malaria exposure in endemic countries in Africa considering
country levels of effective treatment.
AB - BACKGROUND: Malaria prevalence, clinical incidence, treatment, and transmission
rates are dynamically interrelated. Prevalence is often considered a measure of
malaria transmission, but treatment of clinical malaria reduces prevalence, and
consequently also infectiousness to the mosquito vector and onward transmission.
The impact of the frequency of treatment on prevalence in a population is
generally not considered. This can lead to potential underestimation of malaria
exposure in settings with good health systems. Furthermore, these dynamical
relationships between prevalence, treatment, and transmission have not generally
been taken into account in estimates of burden. METHODS: Using prevalence as an
input, estimates of disease incidence and transmission [as the distribution of
the entomological inoculation rate (EIR)] for Plasmodium falciparum have now been
made for 43 countries in Africa using both empirical relationships (that do not
allow for treatment) and OpenMalaria dynamic micro-simulation models (that
explicitly include the effects of treatment). For each estimate, prevalence
inputs were taken from geo-statistical models fitted for the year 2010 by the
Malaria Atlas Project to all available observed prevalence data. National level
estimates of the effectiveness of case management in treating clinical attacks
were used as inputs to the estimation of both EIR and disease incidence by the
dynamic models. RESULTS AND CONCLUSIONS: When coverage of effective treatment is
taken into account, higher country level estimates of average EIR and thus higher
disease burden, are obtained for a given prevalence level, especially where
access to treatment is high, and prevalence relatively low. These methods provide
a unified framework for comparison of both the immediate and longer-term impacts
of case management and of preventive interventions.
PMID- 26437799
TI - Cancer Cell Imaging Using in Situ Generated Gold Nanoclusters.
AB - In situ generated fluorescent gold nanoclusters (Au-NCs) are used for bio-imaging
of three human cancer cells, namely, lung (A549), breast (MCF7), and colon
(HCT116), by confocal microscopy. The amount of Au-NCs in non-cancer cells (WI38
and MCF10A) is 20-40 times less than those in the corresponding cancer cells. The
presence of a larger amount of glutathione (GSH) capped Au-NCs in the cancer cell
is ascribed to a higher glutathione level in cancer cells. The Au-NCs exhibit
fluorescence maxima at 490-530 nm inside the cancer cells. The fluorescence
maxima and matrix-assisted laser desorption ionization (MALDI) mass spectrometry
suggest that the fluorescent Au-NCs consist of GSH capped clusters with a core
structure (Au8-13). Time-resolved confocal microscopy indicates a nanosecond (1-3
ns) lifetime of the Au-NCs inside the cells. This rules out the formation of
aggregated Au-thiolate complexes, which typically exhibit microsecond (~1000 ns)
lifetimes. Fluorescence correlation spectroscopy (FCS) in live cells indicates
that the size of the Au-NCs is ~1-2 nm. For in situ generation, we used a
conjugate consisting of a room-temperature ionic liquid (RTIL, [pmim][Br]) and
HAuCl4. Cytotoxicity studies indicate that the conjugate, [pmim][AuCl4], is non
toxic for both cancer and non-cancer cells.
PMID- 26437800
TI - Experiencing Functional Electrical Stimulation Roots on Education, and Clinical
Developments in Paraplegia and Tetraplegia With Technological Innovation.
AB - Cybernetics-based concepts can allow for complete independence for paralyzed
individuals, including sensory motor recovery. Spinal cord injuries are
responsible for a huge stress on health and a financial burden to society. This
article focuses on novel procedures such as functional diagnosis for paraplegics
and tetraplegics, cybertherapies toward lessening comorbidities such as
cardiovascular diseases, osteoporosis, etc., and the production of new technology
for upper and lower limb control. Functional electrical stimulation reflects a
unique opportunity for bipedal gait to be achieved by paraplegics and
tetraplegics. Education and training of undergraduates and postgraduates in
engineering and life sciences have also been a major aim of this work.
PMID- 26437802
TI - Spontaneous Heterotopic Pregnancy Presenting with Hemoperitoneum.
AB - BACKGROUND: Heterotopic pregnancy is a condition in which intra- and extrauterine
pregnancies occur at the same time. Spontaneous heterotopic pregnancy is a rare
event, with incidences ranging from 1 in 30,000 pregnancies to as high as 1 in 6
pregnancies assisted by reproductive technology. CASE REPORT: A 34-year-old woman
presented with a 10-week history of amenorrhea, pelvic pain, and generally
feeling unwell. Ultrasonography revealed a 10-week intrauterine viable pregnancy
and free fluid in the abdominal cavity. Emergency laparotomy was performed and a
ruptured tubal ectopic pregnancy was encountered on the right tube with
hemoperitoneum. Salpingectomy was performed. Her intrauterine pregnancy was
intact with positive fetal cardiac activity when she was discharged. WHY SHOULD
AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Heterotopic pregnancy should be kept in
the differential diagnosis of any patient with an intrauterine pregnancy
presenting with abdominal pain, abdominal tenderness, or free fluid in the
abdominal cavity.
PMID- 26437803
TI - Spontaneous Adrenal Hemorrhage in Pregnancy Presenting as a Pulmonary Embolism.
PMID- 26437805
TI - Acute Basilar Artery Thrombosis.
PMID- 26437804
TI - Mad Honey Poisoning-Related Hypothermia: A Case Series.
AB - BACKGROUND: Mad honey-related intoxication frequently leads to bradycardia,
hypotension, and syncope. Hypothermia is a potentially life-threatening condition
if not identified early and treated appropriately. CASE REPORT: Three patients
are reviewed. Patient 1 was a 66-year-old man who presented to the emergency
department with nausea, vomiting, and faintness beginning 2 h after consuming
honey. His temperature was 34 degrees C, his blood pressure was 70/40 mm Hg, and
his heart rate was 30 beats/min. Patient 2, a 57-year-old man, presented to the
emergency department with headache, feeling cold, and faintness beginning 3 h
after consuming honey. His temperature was 35 degrees C, his blood pressure was
60/40 mm Hg, and his heart rate was 46 beats/min. Patient 3 was a 79-year-old
woman who presented with nausea, vomiting, and headache 2 h after consuming
honey. Her temperature was 35 degrees C, her blood pressure was 70/40 mm Hg, and
her heart rate was 40 beats/min. All 3 patients were discharged in good condition
after appropriate therapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?:
Bradycardia and hypotension are frequently encountered in mad honey intoxication.
However, intoxication accompanied by hypothermia has attracted little attention
to date.
PMID- 26437801
TI - Copper Transport Protein Antioxidant-1 Promotes Inflammatory Neovascularization
via Chaperone and Transcription Factor Function.
AB - Copper (Cu), an essential micronutrient, plays a fundamental role in inflammation
and angiogenesis; however, its precise mechanism remains undefined. Here we
uncover a novel role of Cu transport protein Antioxidant-1 (Atox1), which is
originally appreciated as a Cu chaperone and recently discovered as a Cu
dependent transcription factor, in inflammatory neovascularization. Atox1
expression is upregulated in patients and mice with critical limb ischemia. Atox1
deficient mice show impaired limb perfusion recovery with reduced arteriogenesis,
angiogenesis, and recruitment of inflammatory cells. In vivo intravital
microscopy, bone marrow reconstitution, and Atox1 gene transfer in Atox1(-/-)
mice show that Atox1 in endothelial cells (ECs) is essential for
neovascularization and recruitment of inflammatory cells which release VEGF and
TNFalpha. Mechanistically, Atox1-depleted ECs demonstrate that Cu chaperone
function of Atox1 mediated through Cu transporter ATP7A is required for VEGF
induced angiogenesis via activation of Cu enzyme lysyl oxidase. Moreover, Atox1
functions as a Cu-dependent transcription factor for NADPH oxidase organizer
p47phox, thereby increasing ROS-NFkappaB-VCAM-1/ICAM-1 expression and monocyte
adhesion in ECs inflamed with TNFalpha in an ATP7A-independent manner. These
findings demonstrate a novel linkage between Atox1 and NADPH oxidase involved in
inflammatory neovascularization and suggest Atox1 as a potential therapeutic
target for treatment of ischemic disease.
PMID- 26437806
TI - Solitary Extramedullary Multiple Myeloma Presenting with Small Bowel Obstruction.
PMID- 26437807
TI - Venolymphatic Malformation of the Labia in a 12-Year-Old Child.
PMID- 26437809
TI - Can state ownership of the tobacco industry really advance tobacco control?
PMID- 26437808
TI - Estimating the 'consumer surplus' for branded versus standardised tobacco
packaging.
AB - BACKGROUND: Tobacco companies question whether standardised (or 'plain')
packaging will change smokers' behaviour. We addressed this question by
estimating how standardised packaging compared to a proven tobacco control
intervention, price increases through excise taxes, thus providing a quantitative
measure of standardised packaging's likely effect. METHODS: We conducted an
online study of 311 New Zealand smokers aged 18 years and above that comprised a
willingness-to-pay task comparing a branded and a standardised pack at four
different price levels, and a choice experiment. The latter used an alternative
specific design, where the alternatives were a branded pack or a standardised
pack, with warning theme and price varied for each pack. RESULTS: Respondents had
higher purchase likelihoods for the branded pack (with a 30% warning) than the
standardised pack (with a 75% warning) at each price level tested, and, on
average, were willing to pay approximately 5% more for a branded pack. The choice
experiment produced a very similar estimate of 'consumer surplus' for a branded
pack. However, the size of the 'consumer surplus' varied between warning themes
and by respondents' demographic characteristics. CONCLUSIONS: These two
experiments suggest standardised packaging and larger warning labels could have a
similar overall effect on adult New Zealand smokers as a 5% tobacco price
increase. The findings provide further evidence for the efficacy of standardised
packaging, which focuses primarily on reducing youth initiation, and suggest this
measure will also bring notable benefits to adult smokers.
PMID- 26437810
TI - Production of Recombinant Adeno-associated Virus Vectors Using Suspension HEK293
Cells and Continuous Harvest of Vector From the Culture Media for GMP FIX and
FLT1 Clinical Vector.
AB - Adeno-associated virus (AAV) has shown great promise as a gene therapy vector in
multiple aspects of preclinical and clinical applications. Many developments
including new serotypes as well as self-complementary vectors are now entering
the clinic. With these ongoing vector developments, continued effort has been
focused on scalable manufacturing processes that can efficiently generate high
titer, highly pure, and potent quantities of rAAV vectors. Utilizing the
relatively simple and efficient transfection system of HEK293 cells as a starting
point, we have successfully adapted an adherent HEK293 cell line from a qualified
clinical master cell bank to grow in animal component-free suspension conditions
in shaker flasks and WAVE bioreactors that allows for rapid and scalable rAAV
production. Using the triple transfection method, the suspension HEK293 cell line
generates greater than 1 * 10(5) vector genome containing particles (vg)/cell or
greater than 1 * 10(14) vg/l of cell culture when harvested 48 hours post
transfection. To achieve these yields, a number of variables were optimized such
as selection of a compatible serum-free suspension media that supports both
growth and transfection, selection of a transfection reagent, transfection
conditions and cell density. A universal purification strategy, based on ion
exchange chromatography methods, was also developed that results in high-purity
vector preps of AAV serotypes 1-6, 8, 9 and various chimeric capsids tested. This
user-friendly process can be completed within 1 week, results in high full to
empty particle ratios (>90% full particles), provides postpurification yields (>1
* 10(13) vg/l) and purity suitable for clinical applications and is universal
with respect to all serotypes and chimeric particles. To date, this scalable
manufacturing technology has been utilized to manufacture GMP phase 1 clinical
AAV vectors for retinal neovascularization (AAV2), Hemophilia B (scAAV8), giant
axonal neuropathy (scAAV9), and retinitis pigmentosa (AAV2), which have been
administered into patients. In addition, we report a minimum of a fivefold
increase in overall vector production by implementing a perfusion method that
entails harvesting rAAV from the culture media at numerous time-points post
transfection.
PMID- 26437812
TI - "Difficult asthma": not as easy as you think.
PMID- 26437811
TI - Full-length nucleotide sequences of 30 common SLC44A2 alleles encoding human
neutrophil antigen-3.
AB - BACKGROUND: Human neutrophil antigen-3a (HNA-3a) alloantibodies can cause severe
transfusion-related acute lung injury. The frequencies of the single-nucleotide
polymorphisms (SNPs) indicative of the two clinically relevant HNA-3a/b antigens
are known in many populations. In this study, we determined the full-length
nucleotide sequence of common SLC44A2 alleles encoding the choline transporter
like protein-2 that harbors HNA-3a/b antigens. STUDY DESIGN AND METHODS: A method
was devised to determine the full-length coding sequence (CDS) and adjacent
intron sequences from genomic DNA by eight polymerase chain reaction
amplifications covering all 22 SLC44A2 exons. Samples from 200 African American,
96 Caucasian, two Hispanic, and four Asian blood donors were analyzed. We
developed a decision tree to determine alleles (confirmed haplotypes) from the
genotype data. RESULTS: A total of 10 SNPs were detected in the SLC44A2 CDS. The
noncoding sequences harbored an additional 28 SNPs (one in the 5'-untranslated
region [UTR]; 23 in the introns; and four in the 3'-UTR). No SNP indicative of a
nonfunctional allele was detected. The nucleotide sequences for 30 SLC44A2
alleles (haplotypes) were confirmed. There may be 66 haplotypes among the 604
chromosomes screened. CONCLUSIONS: We found 38 SNPs, including one novel SNP, in
8192 nucleotides covering the CDS of the SLC44A2 gene among 302 blood donors.
Population frequencies of these SNPs were established for African Americans and
Caucasians. Because alleles encoding HNA-3b are more common than non-functional
SLC44A2 alleles, we confirmed our previous postulate that African American donors
are less likely to form HNA-3a antibodies compared to Caucasians.
PMID- 26437813
TI - Is the eosinophil a leading villain in lung function decline?
PMID- 26437814
TI - Visceral pleural invasion: crossing a (thin) line.
PMID- 26437815
TI - Prostacyclin and oral vasodilator therapy in sarcoidosis-associated pulmonary
hypertension: a retrospective case series.
AB - BACKGROUND: It is unclear whether recent advances in pulmonary arterial
hypertension therapy can be safely applied to sarcoidosis-associated pulmonary
hypertension (SAPH). Evidence for prostacyclin (PG) therapy in SAPH is limited.
METHODS: We conducted a single-center, retrospective review of 46 patients with
sarcoidosis, 26 of whom had SAPH. Thirteen received PG as monotherapy or in
combination with oral vasodilators. RESULTS: Follow-up right-sided heart
catheterization at a mean of 12.7 months revealed improved cardiac output,
cardiac index, and pulmonary vascular resistance. Functional class and N-terminal
pro-brain natriuretic peptide levels also improved in patients treated with PG.
No significant change in oxygen requirement was seen with vasodilator therapy
initiation. At 2 years, 15 patients with SAPH survived, including eight on PG,
and at 5 years, seven survived, including five on PG. Survival was significantly
reduced in patients with SAPH compared with patients who had sarcoidosis without
pulmonary hypertension. Multivariate analysis demonstrated that the use of PG
therapy in SAPH is not associated with increased mortality. CONCLUSIONS: Many
patients with severe SAPH showed significant hemodynamic and clinical improvement
on long-term IV or subcutaneous PG therapy and had survival outcomes similar to
patients with moderate SAPH on oral vasodilator therapy.
PMID- 26437817
TI - A man in his 50s with septic shock from an occult source.
PMID- 26437816
TI - Three-dimensional modeled T-tube design and insertion in a patient with tracheal
dehiscence.
AB - A 68-year-old man with recurrent medullary thyroid cancer underwent cervical
tracheal resection and reconstruction. His course was complicated by tracheal
anastomotic dehiscence, right carotid blowout, and ultimately cervical
tracheoplasty with AlloDerm. Given the complex vascular interventions and upper
airway anatomy, a custom-designed Montgomery T-tube was designed for him. Three
dimensional digital reconstruction of his upper airways was obtained from a CT
scan. The T-tube was designed and fabricated based on the digital trachea model
and was subsequently placed successfully. Follow-up CT scan and bronchoscopy
confirmed placement and revealed no granulation tissue at 4 weeks. The patient
was discharged to home with the ability to phonate. To our knowledge, this is the
first demonstration of three-dimensional modeling of an upper-airway defect with
subsequent T-tube design using engineering software. The success of this case
demonstrates a possible avenue for personalized airway prosthesis design and
manufacturing in the future.
PMID- 26437818
TI - A 33-year-old man with multiple bilateral pulmonary pseudoaneurysms.
AB - A 33-year-old man, never smoker, presented with acute-onset dyspnea secondary to
bilateral pulmonary emboli. Echocardiography at the time revealed a right atrial
myxoma, for which he underwent resection, followed by anticipated lifelong
therapeutic anticoagulation therapy.
PMID- 26437819
TI - A 44-year-old man with bilateral pneumothorax.
AB - A 44-year-old man presented with a 3-day history of persistent upper-back pain,
chest discomfort, and dyspnea. He denied any precipitating events such as trauma
or vigorous activity before the presentation of symptoms. His exercise capacity
had been excellent. He is a lifetime nonsmoker and never had significant lung
problems apart from intermittent asthma for which he had several ED visits in the
past. Chest CT scan performed during an asthma exacerbation 2 years earlier
demonstrated two left-side lung blebs. He had no prior surgical procedures.
PMID- 26437820
TI - A 60-year-old woman with cough, dyspnea, and atelectasis 19 years after liver
transplant.
AB - A 60-year-old black woman presented with nonproductive cough of 1-month duration.
She had also experienced rapidly progressive dyspnea for 1 week and one bout of
vomiting a day before presentation. Her symptoms had failed to improve with a
course of amoxicillin-clavulanate. Her medical history was significant for
diabetes mellitus and liver transplant 19 years earlier for hepatitis C
cirrhosis, for which she was receiving tacrolimus and mycophenolate. She was a
current smoker with 40 pack-years of smoking history.
PMID- 26437821
TI - Therapy for pulmonary arterial hypertension: approved dosages should be
prescribed in clinical practice.
PMID- 26437822
TI - High-flow nasal cannula can be used outside the ICU.
PMID- 26437823
TI - Response.
PMID- 26437824
TI - Endosonography: esophagus is better!
PMID- 26437825
TI - Response.
PMID- 26437826
TI - Does circulating IL-17 identify a subset of patients with idiopathic pulmonary
arterial hypertension?
PMID- 26437827
TI - Response.
PMID- 26437828
TI - Using clinical pathways to assess interventions to prevent COPD readmissions.
PMID- 26437829
TI - Response.
PMID- 26437830
TI - Cognitive effects following acute wild blueberry supplementation in 7- to 10-year
old children.
AB - PURPOSE: Previously, anthocyanin-rich blueberry treatments have shown positive
effects on cognition in both animals and human adults. However, little research
has considered whether these benefits transfer to children. Here we describe an
acute time-course and dose-response investigation considering whether these
cognitive benefits extend to children. METHODS: Using a double-blind cross-over
design, on three occasions children (n = 21; 7-10 years) consumed placebo
(vehicle) or blueberry drinks containing 15 or 30 g freeze-dried wild blueberry
(WBB) powder. A cognitive battery including tests of verbal memory, word
recognition, response interference, response inhibition and levels of processing
was performed at baseline, and 1.15, 3 and 6 h following treatment. RESULTS:
Significant WBB-related improvements included final immediate recall at 1.15 h,
delayed word recognition sustained over each period, and accuracy on cognitively
demanding incongruent trials in the interference task at 3 h. Importantly, across
all measures, cognitive performance improved, consistent with a dose-response
model, with the best performance following 30 g WBB and the worst following
vehicle. CONCLUSION: Findings demonstrate WBB-related cognitive improvements in 7
to 10-year-old children. These effects would seem to be particularly sensitive
to the cognitive demand of task.
PMID- 26437831
TI - Digestion-resistant maltodextrin effects on colonic transit time and stool
weight: a randomized controlled clinical study.
AB - PURPOSE: Increased awareness of the importance of dietary fibre has led to
increased interest in "functional" fibre components like digestion-resistant
maltodextrin (RMD). This randomized, placebo-controlled, double-blind study
assessed the effects of RMD in the colonic transit time (CTT) and defecation
characteristics (frequency, stool volume and consistency). METHODS: Sixty-six
healthy adult volunteers (32 men) who did not have a daily defecation habit had a
7-day run-in period before the 21-day intervention period with RMD or placebo.
CTT and segmental CTT (SCTT) were assessed by a single abdominal X-ray film taken
at the end of both periods after radiopaque marker ingestion. Defecation
characteristics and intestinal functions were also assessed, which were self
reported by patients. Intragroup comparisons were evaluated by Student's paired t
test, Bonferroni test and Chi-square test, while time comparisons by analysis of
variance (ANOVA) and time-by-treatment interaction by repeated-measures ANOVA.
RESULTS: Fifty-seven subjects were assessed for CTT (placebo, n = 28; RMD, n =
29). In the RMD group, the total CTT, left SCTT and rectosigmoidal SCTT decreased
significantly compared to baseline (p < 0.01 each; -13.3, -4.7, -8.7 h,
respectively). Significant differences between groups were observed in total CTT
and left SCTT. Significant time-by-treatment interaction was observed in the RMD
group for stool volume (p = 0.014), increasing 56 % compared to baseline (p <
0.01), while remained unchanged in the placebo group. Stool consistency was
improved only in the RMD group (p < 0.01). No adverse effects related to study
products were observed. CONCLUSIONS: The results show that RMD improved CTT,
stool volume, stool consistency and some intestinal functions in a healthy
population.
PMID- 26437832
TI - Intake and sources of gluten in 20- to 75-year-old Danish adults: a national
dietary survey.
AB - PURPOSE: Celiac disease, an immunological response triggered by gluten, affects
~1 % of the Western population. Information concerning gluten intake in the
general population is scarce. We determined intake of gluten from wheat, barley,
rye and oat in the Danish National Survey of Diet and Physical Activity 2005
2008. The study population comprised a random cross-sectional sample of 1494
adults 20-75 years, selected from the Danish Civil Registration System. METHODS:
Protein content in wheat, rye, barley and oat was determined from the National
Danish Food Composition Table and multiplied with the amount of cereal used in
recipes. Amount of gluten was calculated as amount of cereal protein *0.80 for
wheat and oat, *0.65 for rye and *0.50 for barley. Dietary intake was recorded
daily during seven consecutive days in pre-coded food diaries with open-answer
possibilities. RESULTS: Mean total gluten intake was 10.4 +/- 4.4 g/day (10th
90th percentiles; 5.4-16.2 g/day), in men 12.0 +/- 4.6 g/day and 9.0 +/- 3.4
g/day in women. It was higher among men than among women in all age groups (20-75
years; P < 0.0001); however, this difference was eliminated when adjusting for
energy intake. Intake of different gluten sources tended to be higher in men than
in women with the exception of gluten from barley. Total gluten intake decreased
with increasing age (P < 0.0001) as did gluten intake from wheat (P < 0.0001),
whereas intake of gluten from rye (P < 0.0001) and barley (P = 0.001) increased
with increasing age, also when adjusted for energy intake or body weight.
CONCLUSION: This study presents representative population-based data on gluten
intake in Danish adults. Total gluten intake decreased with increasing age.
PMID- 26437833
TI - High resolution structure of an M23 peptidase with a substrate analogue.
AB - LytM is a Staphylococcus aureus autolysin and a homologue of the S. simulans
lysostaphin. Both enzymes are members of M23 metallopeptidase family (MEROPS)
comprising primarily bacterial peptidoglycan hydrolases. LytM occurs naturally in
a latent form, but can be activated by cleavage of an inhibitory N-terminal
proregion. Here, we present a 1.45 A crystal structure of LytM catalytic domain
with a transition state analogue, tetraglycine phosphinate, bound in the active
site. In the electron density, the active site of the peptidase, the phosphinate
and the "diglycine" fragment on the P1' side of the transition state analogue are
very well defined. The density is much poorer or even absent for the P1 side of
the ligand. The structure is consistent with the involvement of His260 and/or
His291 in the activation of the water nucleophile and suggests a possible
catalytic role for Tyr204, which we confirmed by mutagenesis. Possible mechanisms
of catalysis and the structural basis of substrate specificity are discussed
based on the structure analysis.
PMID- 26437834
TI - Choosing Wisely? "It's Complicated!".
PMID- 26437835
TI - Minimising harm in the early pregnancy population.
PMID- 26437836
TI - [The life cycle of Rubella Virus].
AB - Rubella virus (RV), an infectious agent of rubella, is the sole member of the
genus Rubivirus in the family of Togaviridae. RV has a positive-stranded sense
RNA as a genome. A natural host of RV is limited to human, and rubella is
considered to be a childhood disease in general. When woman is infected with RV
during early pregnancy, her fetus may develop severe birth defects known as
congenital rubella syndrome. In this review, the RV life cycle from the virus
entry to budding is illustrated in comparison with those of member viruses of the
genus alphavirus in the same family. The multiple functions of the RV capsid
protein are also introduced.
PMID- 26437837
TI - [Application of artificial DNA-binding proteins and artificial nucleases to
prevention of virus infection: development of virus-resistant plants and protein
based anti-viral drugs].
AB - Various DNA viruses are known to cause severe infectious diseases in both plants
and mammals, including humans. For many of these infectious diseases, we have yet
to find an effective prevention or treatment. Therefore, new methodologies for
the prevention of virus infections in both agricultural crops and humans have
been vigorously sought for a long time. One attractive approach to the prevention
is inhibition of virus replication. We first inhibited virus replication by
blocking binding of a viral replication protein, which initiates virus
replication, to its replication origin, with using an artificial DNA-binding
protein. We demonstrated that this new methodology was very effective in plants
and mammalian cells: especially, we created transgenic plants that were immune to
a geminivirus. We also developed novel protein-based antiviral drugs by fusing a
cell-penetrating peptide to an artificial DNA-binding protein. Furthermore, we
successfully generated a more effective protein-based antiviral, which was one
hundred thousand times more active than the antiviral chemical drug Cidofovia, by
alternatively fusing an DNA-cleaving enzyme to an artificial DNA-binding protein.
Since this artificial protein has little cytotoxicity, it is expected that it
will be used as a new antiviral drug.
PMID- 26437838
TI - [Membrane Binding of Retroviral Gag Proteins].
AB - Location of virus assembly in infected cells has major influences on efficiencies
of virus assembly and release and on post-assembly processes including cell-to
cell transmission. Therefore, for better understanding of virus spread and for
developing new antiviral strategies, it is important to elucidate mechanisms by
which the subcellular site of virus particle assembly is determined. Retrovirus
particle assembly is driven by viral structural protein Gag. In the case of HIV
1, Gag binds to the plasma membrane (PM) via the N-terminal MA domain and forms
nascent particles at this location. Recent studies reveled that PM-specific
phospholipid PI(4,5)P2 plays an important role in directing Gag to the PM through
its interaction with MA. In this review, I will summarize our current
understanding of relationships between retroviral MA domains and phospholipids in
cellular membranes and discuss possible mechanisms by which lipids and other
factors regulate membrane binding and subcellular localization of retroviral Gag
proteins.
PMID- 26437839
TI - [The multifunctional RNA polymerase L protein of non-segmented negative strand
RNA viruses catalyzes unique mRNA capping].
AB - Non-segmented negative strand RNA viruses belonging to the Mononegavirales order
possess RNA-dependent RNA polymerase L proteins within viral particles. The L
protein is a multifunctional enzyme catalyzing viral RNA synthesis and processing
(i.e., mRNA capping, cap methylation, and polyadenylation). Using vesicular
stomatitis virus (VSV) as a prototypic model virus, we have shown that the L
protein catalyzes the unconventional mRNA capping reaction, which is strikingly
different from the eukaryotic reaction. Furthermore, co-transcriptional pre-mRNA
capping with the VSV L protein was found to be required for accurate stop?start
transcription to synthesize full-length mRNAs in vitro and virus propagation in
host cells. This article provides a review of historical and present studies
leading to the elucidation of the molecular mechanism of VSV mRNA capping.
PMID- 26437840
TI - [Rotaviruses].
AB - Rotavirus, a member of the family Reoviridae, was identified as the leading
etiological agent of severe gastroenteritis in infants and young children in
1973. The rotavirus genome is composed of 11 gene segments of double-stranded
(ds)RNA. During the last 40 years, a large amount of basic research on rotavirus
structure, genome, antigen, replication, pathogenesis, epidemiology, immune
responses, and evolution has been accumulated. This article reviews the
fundamental aspects of rotavirology including recent important achievements in
research.
PMID- 26437841
TI - [Orthoreoviruses].
AB - Members of the genus Orthoreovirus in the family Reoviridae are nonenveloped,
icosahedral viruses. Their genomes contain 10 segments of double-stranded RNA
(dsRNA). The orthoreoviruses are divided into two subgroups, the fusogenic and
nonfusogenic reoviruses, based on the ability of the virus to induce cell-to-cell
fusion. The fusogenic subgroup consists of the avian reovirus, baboon reovirus,
pteropine reovirus, and reptilian reovirus, whereas the nonfusogenic subgroup
consists of the prototypical mammalian reovirus (MRV) species. MRVs are highly
tractable experimental models for studies of segmented dsRNA virus replication
and pathogenesis. Moreover, MRVs can selectively kill tumor cells and have been
evaluated as oncolytic agents in clinical trials. This review provides a brief
overview of current knowledge on the virological features of MRVs.
PMID- 26437842
TI - [Reverse genetics systems for orbiviruses reveal the essential mechanisms in
their replication].
AB - The members of Orbivirus genus within the family Reoviridae cause severe
arthropod-born diseases mainly in ruminants and equids. In addition, the
orbiviruses, which can infect humans, have been reported. In the last decade, the
molecular and structural studies for orbiviruses, including Bluetongue virus
(BTV), has made a great progress. Especially, a reverse genetics system (RG) for
BTV, developed soon after Orhoreovirus and Rotavirus, is a major breakthrough.
Here, I introduced the recent findings in orbivirus replication, especially the
function of an enzymatic protein, VP6.
PMID- 26437843
TI - [Plant-infecting reoviruses].
AB - The family Reoviridae separates two subfamilies and consists of 15 genera.
Fourteen viruses in three genera (Phytoreovirus, Oryzavirus, and Fijivirus)
infect plants. The outbreaks of the plant-infecting reoviruses cause sometime the
serious yield loss of rice and maize, and are a menace to safe and efficient food
production in the Southeast Asia. The plant-infecting reoviruses are double
shelled icosahedral particles, from 50 to 80nm in diameter, and include from 10
to 12 segmented double-stranded genomic RNAs depending on the viruses. These
viruses are transmitted in a persistent manner by the vector insects and
replicated in both plants and in their vectors. This review provides a brief
overview of the plant-infecting reoviruses and their recent research progresses
including the strategy for viral controls using transgenic rice plants.
PMID- 26437844
TI - [Diverse double-stranded RNA viruses infecting fungi].
AB - Most of reported fungal viruses (mycoviruses) have double-stranded RNA (dsRNA)
genomes. This may reflect the simple, easy method for mycovirus hunting that
entails detection of dsRNAs as a sign of viral infections. There are an
increasing number of screens of various fungi, particularly phytopathogenic fungi
for viruses pathogenic to host fungi or able to confer hypovirulence to them.
This bases on an attractive research field of biological control of fungal plant
diseases using viruses (virocontrol), mainly targeting important phytopathogenic
fungi. While isolated viruses usually induce asymptomatic symptoms, they show a
considerably high level of diversity. As of 2014, fungal dsRNA viruses are
classified into six families: Reoviridae, Totiviridae, Chrysoviridae,
Partitiviridae, Megabirnaviridae and Quadriviridae. These exclude unassigned
mycoviruses which will definitely be placed into distinct families and/or genera.
In this review article, dsRNA viruses isolated from the kingdom Fungi including
as-yet-unclassified taxa are overviewed. Some recent achievements in the related
field are briefly introduced as well.
PMID- 26437845
TI - Transoral robotic surgery for carcinoma of unknown primary in the head and neck.
AB - Multiple diagnostic and treatment paradigms exist for the management of carcinoma
of unknown primary (CUP) metastatic to cervical lymph nodes. Transoral robotic
surgery (TORS) has emerged as a modality for diagnosis and treatment of CUP,
optimizing identification and resection of the primary tumor, although also
preventing chemotherapy in a subset of patients. This article presents the
authors' treatment paradigm and reviews the literature supporting the use of TORS
in the management of CUP.
PMID- 26437846
TI - Localization-triggered bacterial pathogenesis.
AB - Bacterial infections are becoming an increasing problem worldwide and there is a
need for a deeper understanding of how bacteria turn pathogenic. Here, we suggest
that one answer may be found by taking into account the localization of the
bacteria, both at an anatomical level and at a microenvironment level. Both
commensals and traditional pathogens alter their interaction with the human host
depending on the local surroundings--turning either more or less virulent. These
localization effects could derive from the characteristics of different
anatomical sites but also from local differences within a microenvironment. In
order to understand the adaptive functions of bacterial virulence factors, we
need to study the bacteria in the environments where they have evolved.
PMID- 26437847
TI - A first-principles study of orthorhombic CN as a potential superhard material.
AB - Using first-principles calculations, we have investigated the structural,
electronic, dynamical and mechanical properties of a recently synthesized Pnnm
CN. Phonon dispersion and elastic constant calculations were carried out to
demonstrate the dynamical and mechanical stabilities of the Pnnm structure of CN
at ambient pressure. The electronic band structure suggests that Pnnm-CN is an
insulator with an indirect band gap of about 3.7 eV. First-principles strain
stress relationships at large strains were also simulated to examine the
structural and mechanical properties of Pnnm-CN. The established ideal tensile
strength of ~41 GPa in the <100> direction suggests that CN is a potential
superhard material. The present results provide deep insights for understanding
the mechanical properties of CN and thus are helpful to explore the potential
industrial applications of CN.
PMID- 26437848
TI - Highly Selective Artificial Cholesteryl Crown Ether K(+)-Channels.
AB - The bacterial KcsA channel conducts K(+) cations at high rates while excluding
Na(+) cations. Herein, we report an artificial ion-channel formed by H-bonded
stacks of crown-ethers, where K(+) cation conduction is highly preferred to Na(+)
cations. The macrocycles aligned along the central pore surround the K(+) cations
in a similar manner to the water around the hydrated cation, compensating for the
energetic cost of their dehydration. In contrast, the Na(+) cation does not fit
the macrocyclic binding sites, so its dehydration is not completely compensated.
The present highly K(+)-selective macrocyclic channel may be regarded as a
biomimetic of the KcsA channel.
PMID- 26437849
TI - Meckel's diverticulum as a cause of persistent anaemia.
PMID- 26437851
TI - Treatment of keloid scars with a 1210-nm diode laser in an animal model.
AB - BACKGROUND AND OBJECTIVE: A temperature increase can improve wound healing by
activation of heat shock protein 70 and stimulation of fibroblasts. Since keloids
are a dysfunction of collagen fiber synthesis and organization, this study aimed
to evaluate if a 1,210 nm diode laser could have effects in a new animal model of
keloid scars. STUDY DESIGN/MATERIALS AND METHODS: A total of 39 nude mice were
used for this study. Phototypes IV and V human keloids were grafted into their
backs and after 1 month of healing, the mice were divided into four groups:
Control, Laser, Resection, Resection/Laser. In the Laser group, the keloids were
treated with a 1,210-nm diode-laser with the following parameters: 4 W; 10
seconds; fluence: 51 J/cm(2) ; spot: 18.9 * 3.7 mm(2) . In the Resection group,
surgical intra-lesional excision was performed. In the Resection/Laser group,
keloids were treated with the 1,210-nm laser-diode after surgical intra-lesional
excision. Temperature measurements were made during the laser treatment. Clinical
examination and histological study were performed on the day of treatment and 1
month, 2 months, and 3 months later. RESULTS: Mean temperature measurement was of
44.8 degrees C (42-48 degrees ) in the Laser groups. No healing complications or
keloid proliferation was observed in any group. Keloid histologic characters were
confirmed in all grafts. No histologic particularity was observed in the laser
groups in comparison with the Control and Resection groups. CONCLUSION: First,
this keloid animal model appears to be adapted for laser study. Secondly, the
1,210-nm diode laser does not induce keloid thermal damage in vivo. Further
studies with different 1,210-nm laser diode parameters should be performed in
order to observe significant effects on keloids.
PMID- 26437850
TI - Next-generation-based targeted sequencing as an efficient tool for the study of
the genetic background in Hirschsprung patients.
AB - BACKGROUND: The development of next-generation sequencing (NGS) technologies has
a great impact in the human variation detection given their high-throughput.
These techniques are particularly helpful for the evaluation of the genetic
background in disorders of complex genetic etiology such as Hirschsprung disease
(HSCR). The purpose of this study was the design of a panel of HSCR associated
genes as a rapid and efficient tool to perform genetic screening in a series of
patients. METHODS: We have performed NGS-based targeted sequencing (454-GS
Junior) using a panel containing 26 associated or candidate genes for HSCR in a
group of 11 selected HSCR patients. RESULTS: The average percentage of covered
bases was of 97%, the 91.4% of the targeted bases were covered with depth above
20X and the mean coverage was 422X. In addition, we have found a total of 13 new
coding variants and 11 new variants within regulatory regions among our patients.
These outcomes allowed us to re-evaluate the genetic component associated to HSCR
in these patients. CONCLUSIONS: Our validated NGS panel constitutes an optimum
method for the identification of new variants in our patients. This approach
could be used for a fast, reliable and more thorough genetic screening in future
series of patients.
PMID- 26437852
TI - One in four GP appointments can be avoided, says report.
PMID- 26437853
TI - Effect of adjuvant chemotherapy on recurrence-free survival varies by neo
adjuvant treatment in patients with stage III rectal cancer.
AB - INTRODUCTION: Adjuvant chemotherapy still is a controversial therapy for rectal
cancer patients. The aim of this study was to analyze the effect of adjuvant
chemotherapy on recurrence-free survival (RFS) for patients with stage III rectal
cancer treated in clinical practice, taking into account which neo-adjuvant
treatment patients received. METHODS: Patients from regions in the Netherlands
diagnosed between 1996 and 2013 with pathological stage III rectal cancer who
received short-course radiotherapy, chemoradiation or no neo-adjuvant treatment
and who underwent surgery were included. After stratification by neo-adjuvant
treatment, 5-year RFS according to adjuvant chemotherapy receipt was calculated
using Kaplan-Meier curves. Cox regression was used to discriminate the
independent effect of adjuvant chemotherapy on the risk of recurrence/death.
RESULTS: The study population consisted of 829 patients, of whom 537 (65%)
patients received short-course radiotherapy, 128 (15%) patients received
chemoradiation and 164 (20%) patients received no neo-adjuvant treatment.
Adjuvant chemotherapy was administered to 152 (18%) patients. Adjuvant
chemotherapy was associated with improved 5-year RFS for patients who received
short-course radiotherapy (61% vs. 46%, p = 0.005) and for patients who did not
receive any neo-adjuvant treatment (70% vs. 28%, p < 0.0001). In multivariable
analyses, adjuvant chemotherapy was associated with a reduced risk of
recurrence/death for patients treated with short-course radiotherapy (HR 0.65,
95% CI 0.46-0.93) and for patients without neo-adjuvant treatment (HR 0.35, 95%
CI 0.18-0.71), but not for patients treated with chemoradiation (HR 1.11, 95% CI
0.51-2.41). CONCLUSION: Among patients with stage III rectal cancer, the effect
of adjuvant chemotherapy on RFS seems to vary by neo-adjuvant treatment.
PMID- 26437854
TI - Reply to: "Is there a role for axillary reverse mapping in the current management
of breast cancer treatment?".
PMID- 26437855
TI - Is radiofrequency ablation of lung metastases the most radical treatment?
PMID- 26437856
TI - Intraspinal serotonergic neurons consist of two, temporally distinct populations
in developing zebrafish.
AB - Zebrafish intraspinal serotonergic neuron (ISN) morphology and distribution have
been examined in detail at different ages; however, some aspects of the
development of these cells remain unclear. Although antibodies to serotonin (5
HT) have detected ISNs in the ventral spinal cord of embryos, larvae, and adults,
the only tryptophan hydroxylase (tph) transcript that has been described in the
spinal cord is tph1a. Paradoxically, spinal tph1a is only expressed transiently
in embryos, which brings the source of 5-HT in the ISNs of larvae and adults into
question. Because the pet1 and tph2 promoters drive transgene expression in the
spinal cord, we hypothesized that tph2 is expressed in spinal cords of zebrafish
larvae. We confirmed this hypothesis through in situ hybridization. Next, we used
5-HT antibody labeling and transgenic markers of tph2-expressing neurons to
identify a transient population of ISNs in embryos that was distinct from ISNs
that appeared later in development. The existence of separate ISN populations may
not have been recognized previously due to their shared location in the ventral
spinal cord. Finally, we used transgenic markers and immunohistochemical labeling
to identify the transient ISN population as GABAergic Kolmer-Agduhr double-prime
(KA") neurons. Altogether, this study revealed a novel developmental paradigm in
which KA" neurons are transiently serotonergic before the appearance of a stable
population of tph2-expressing ISNs.
PMID- 26437857
TI - Multicopper oxidase-1 is required for iron homeostasis in Malpighian tubules of
Helicoverpa armigera.
AB - Multicopper oxidases (MCOs) are enzymes that contain 10 conserved histidine
residues and 1 cysteine residue. MCO1 has been extensively investigated in the
midgut because this MCO is implicated in ascorbate oxidation, iron homeostasis
and immune responses. However, information regarding the action of MCO1 in
Malpighian tubules is limited. In this study, Helicoverpa armigera was used as a
model to investigate the function of MCO1 in Malpighian tubules. Sequence
analysis results revealed that HaMCO1 exhibits typical MCO characteristics, with
10 histidine and 1 cysteine residues for copper ion binding. HaMCO1 was also
found to be highly abundant in Malpighian tubules. Temporal expression patterns
indicated that HaMCO1 is mainly expressed during larval molting stages. Hormone
treatments [the molting hormone 20-hydroxyecdysone (20E) and juvenile hormone
(JH)] revealed that 20E inhibits HaMCO1 transcript expression via its heterodimer
receptor, which consists of ecdysone receptor (EcR) and ultraspiracle (USP), and
that JH counteracts the action of 20E to activate HaMCO1 transcript expression
via its intracellular receptor methoprene-tolerant (Met). HaMCO1 knockdown caused
a significant decrease in iron accumulation and also significantly reduced
transferrin and ferritin transcript expression. Therefore, HaMCO1 is coordinately
regulated by 20E and JH and is required for iron homeostasis in Malpighian
tubules.
PMID- 26437858
TI - Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in
cancer stem cells.
AB - The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs),
cancers occurring increasingly in children to young adults, is poorly understood.
We present a transplantable tumour line, maintained in immune-compromised mice,
and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq
analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA)
characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for
cancer stem cells as indicated by limited dilution tumourigenicity assays,
spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model,
with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for
expression of endodermal stem cell traits. Transcriptomic analyses of the tumour
line and of multiple, normal hepatic lineage stages reveal a gene signature for
hFL-HCCs closely resembling that of biliary tree stem cells--newly discovered
precursors for liver and pancreas. This model offers unprecedented opportunities
to investigate mechanisms underlying hFL-HCCs pathogenesis and potential
therapies.
PMID- 26437859
TI - Genetic identification of cytomegaloviruses in a rural population of Cote
d'Ivoire.
AB - BACKGROUND: Cytomegaloviruses (CMVs) are herpesviruses that infect many mammalian
species, including humans. Infection generally passes undetected, but the virus
can cause serious disease in individuals with impaired immune function. Human CMV
(HCMV) is circulating with high seroprevalence (60-100 %) on all continents.
However, little information is available on HCMV genoprevalence and genetic
diversity in subsaharan Africa, especially in rural areas of West Africa that are
at high risk of human-to-human HCMV transmission. In addition, there is a
potential for zoonotic spillover of pathogens through bushmeat hunting and
handling in these areas as shown for various retroviruses. Although HCMV and
nonhuman CMVs are regarded as species-specific, potential human infection with
CMVs of non-human primate (NHP) origin, shown to circulate in the local NHP
population, has not been studied. FINDINGS: Analysis of 657 human oral swabs and
fecal samples collected from 518 individuals living in 8 villages of Cote
d'Ivoire with generic PCR for identification of human and NHP CMVs revealed
shedding of HCMV in 2.5 % of the individuals. Determination of glycoprotein B
sequences showed identity with strains Towne, AD169 and Toledo, respectively. NHP
CMV sequences were not detected. CONCLUSIONS: HCMV is actively circulating in a
proportion of the rural Cote d'Ivoire human population with circulating strains
being closely related to those previously identified in non-African countries.
The lack of NHP CMVs in human populations in an environment conducive to cross
species infection supports zoonotic transmission of CMVs to humans being at most
a rare event.
PMID- 26437860
TI - Malaria ecology along the Thailand-Myanmar border.
AB - BACKGROUND: Malaria in Southeast Asia frequently clusters along international
borders. For example, while most of Thailand is malaria free, the border region
shared with Myanmar continues to have endemic malaria. This spatial pattern is
the result of complex interactions between landscape, humans, mosquito vectors,
and malaria parasites. An understanding of these complex ecological and socio
cultural interactions is important for designing and implementing malaria
elimination efforts in the region. This article offers an ecological perspective
on the malaria situation along the Thailand-Myanmar border. DISCUSSION: This
border region is long (2000 km), mountainous, and the environment ranges from
thick forests to growing urban settlements and wet-rice fields. It is also a
biologically diverse region. All five species of malaria known to naturally
infect humans are present. At least three mosquito vector species complexes, with
widely varying behavioural characteristics, exist in the area. The region is also
a hub for ethnic diversity, being home to over ten different ethnolinguistic
groups, several of which have been engaged in conflict with the Myanmar
government now for over half a century. Given the biological and ethnic
diversity, as well as the complex socio-political context, malaria control and
elimination in the region is challenging. CONCLUSION: Despite these complexities,
multipronged approaches including collaborations with multiple local
organizations, quick access to diagnosis and treatment, prevention of mosquito
bites, radical cure of parasites, and mass drug administration appear to be
drastically decreasing Plasmodium falciparum infections. Such approaches remain
crucial as the region moves toward elimination of P. falciparum and potentially
Plasmodium vivax.
PMID- 26437861
TI - Chemomodulatory Potential of Flaxseed Oil Against DMBA/Croton Oil-Induced Skin
Carcinogenesis in Mice.
AB - The present study was conducted to evaluate the potential of flaxseed oil to
prevent chemically induced skin cancer in mice. Cancer was induced on 2-stage
skin carcinogenesis model by single topical application of 7,12 dimethylbenz
[a]anthracene (DMBA), as, initiator, and two weeks later it was promoted by
croton oil treatment thrice a week on the dorsal surface of mice for 16 weeks.
Flaxseed oil (FSO; 100uL/animal/d) was orally administered 1 week before and 1
week after DMBA application (Peri-initiation stage). The animals of the FSO
administered group showed a significant reduction in tumor incidence (76.67%),
cumulative number of tumors (37), tumor yield (3.7), and tumor burden (4.81) when
compared with the carcinogen-treated control animals. Biochemical parameters in
skin and liver tissue such as LPO and phase I enzymes were significantly (P <
.01) reduced in the FSO-treated experimental group, whereas the phase II enzymes
(GST, DT-diaphorase) and antioxidant parameters (GSH, GPx, SOD, catalase, and
vitamin C) exhibited a significant (P < .01) elevation when compared with the
animals of the carcinogen-treated control group. Histopathological alterations in
the carcinogen-treated control animals were also observed in the form of
epidermal hyperplasia, keratinized pearl formation, and acanthosis in skin and
tumors, whereas these were found to be reduced after FSO administration. The
results of the present study demonstrate that the oral administration of FSO has
the potential to modulate the levels of LPO, antioxidants, and detoxification
enzymes in the DMBA-croton oil-induced skin carcinogenesis in mice.
PMID- 26437863
TI - Wisdom at the End of Life: An Analysis of Mediating and Moderating Relations
Between Wisdom and Subjective Well-Being.
AB - OBJECTIVES: Several studies have shown that wisdom, measured as an integration of
cognitive, reflective, and compassionate dimensions, is positively related to
subjective well-being in old age. This study investigated whether wisdom might be
particularly beneficial for people at the end of life, when extrinsic means to
increase well-being largely disappear, and whether the association between wisdom
and well-being is mediated by mastery and purpose in life. METHODS: Samples of
156 older community residents (M = 71 years) and 41 older hospice patients and
nursing home residents (M = 77 years) were analyzed, using a moderated and
mediated path model. RESULTS: (a) Wisdom was positively related to subjective
well-being in the later years, even after controlling for physical health,
socioeconomic status, financial situation, social involvement, age, gender, race,
and marital status. (b) The association between wisdom and well-being was
significantly stronger in the nursing home and hospice sample than the community
sample. (c) The relation between wisdom and well-being was partially mediated by
purpose in life, both directly and via a sense of mastery. CONCLUSION: Aging well
at the end of life might depend to a larger extent on psychosocial growth across
the life course than on present circumstances.
PMID- 26437862
TI - Associations Among Individuals' Perceptions of Future Time, Individual Resources,
and Subjective Well-Being in Old Age.
AB - Objectives: Perceptions of future time are of key interest to aging research
because of their implications for subjective well-being. Interestingly,
perceptions about future time are only moderately associated with age when
looking at the second half of life, pointing to a vast heterogeneity in future
time perceptions among older adults. We examine associations between future time
perceptions, age, and subjective well-being across two studies, including
moderations by individual resources. Method: Using data from the Berlin Aging
Study (N = 516; Mage = 85 years), we link one operationalization (subjective
nearness to death) and age to subjective well-being. Using Health and Retirement
Study data (N = 2,596; Mage = 77 years), we examine associations of another
future time perception indicator (subjective future life expectancy) and age with
subjective well-being. Results: Consistent across studies, perceptions of limited
time left were associated with poorer subjective well-being (lower life
satisfaction and positive affect; more negative affect and depressive symptoms).
Importantly, individual resources moderated future time perception-subjective
well-being associations with those of better health exhibiting reduced future
time perception-subjective well-being associations. Discussion: We discuss our
findings in the context of the Model of Strength and Vulnerability Integration.
PMID- 26437864
TI - Short-term suppression of A315T mutant human TDP-43 expression improves
functional deficits in a novel inducible transgenic mouse model of FTLD-TDP and
ALS.
AB - The nuclear transactive response DNA-binding protein 43 (TDP-43) undergoes
relocalization to the cytoplasm with formation of cytoplasmic deposits in neurons
in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration
(FTLD). Pathogenic mutations in the TDP-43-encoding TARDBP gene in familial ALS
as well as non-mutant human TDP-43 have been utilized to model FTD/ALS in cell
culture and animals, including mice. Here, we report novel A315T mutant TDP-43
transgenic mice, iTDP-43(A315T), with controlled neuronal over-expression.
Constitutive expression of human TDP-43(A315T) resulted in pronounced early-onset
and progressive neurodegeneration, which was associated with compromised motor
performance, spatial memory and disinhibition. Muscle atrophy resulted in reduced
grip strength. Cortical degeneration presented with pronounced astrocyte
activation. Using differential protein extraction from iTDP-43(A315T) brains, we
found cytoplasmic localization, fragmentation, phosphorylation and ubiquitination
and insolubility of TDP-43. Surprisingly, suppression of human TDP-43(A315T)
expression in mice with overt neurodegeneration for only 1 week was sufficient to
significantly improve motor and behavioral deficits, and reduce astrogliosis. Our
data suggest that functional deficits in iTDP-43(A315T) mice are at least in part
a direct and transient effect of the presence of TDP-43(A315T). Furthermore, it
illustrates the compensatory capacity of compromised neurons once transgenic TDP
43 is removed, with implications for future treatments.
PMID- 26437866
TI - Predictive factors for perioperative blood transfusions in partial nephrectomy
for renal masses.
AB - BACKGROUND: Allogeneic perioperative blood transfusions (PBT) have been
associated with higher rates of postoperative complications and tumour recurrence
in a number of malignancies. This study evaluates the risk factors for PBT in
patients undergoing partial nephrectomy (PN), in order to identify patients who
could benefit from alternatives to allogenic blood. METHODS: Data on 822 patients
who underwent elective PN between 1988 and 2013 were analysed. Patient
demographics and clinicopathologic variables were collected retrospectively. PBT
was defined as transfusion of allogeneic red blood cells during PN (in the
operating-room) or postoperative hospitalization. RESULTS: Of the 822 patients,
122 (14.8%) received PBT. Of these, 45.9% were transfused intraoperatively and
47.5% in the postoperative period. Only 14.3% of the patients who were transfused
intraoperatively required additional postoperative transfusions. On multivariable
analysis, age >=65 (P < 0.01), lower preoperative haemoglobin levels (P < 0.001),
larger renal masses (P < 0.001), central lesions (P < 0.01) and cumulative
surgical experience (P < 0.001) were found to be associated with higher rate of
PBT. CONCLUSIONS: Age, low preoperative haemoglobin level, lesion size, surgeons'
experience and central renal lesions are independent pre-operative risk factors
for PBT in patients undergoing PN. Evaluation of these risk factors prior to
surgery may be helpful in constituting guidelines for a more responsible use of
allogeneic blood and its alternatives.
PMID- 26437865
TI - Novel clinical associations with specific C9ORF72 transcripts in patients with
repeat expansions in C9ORF72.
AB - The loss of chromosome 9 open reading frame 72 (C9ORF72) expression, associated
with C9ORF72 repeat expansions, has not been examined systematically. Three
C9ORF72 transcript variants have been described thus far; the GGGGCC repeat is
located between two non-coding exons (exon 1a and exon 1b) in the promoter region
of transcript variant 2 (NM_018325.4) or in the first intron of variant 1
(NM_145005.6) and variant 3 (NM_001256054.2). We studied C9ORF72 expression in
expansion carriers (n = 56) for whom cerebellum and/or frontal cortex was
available. Using quantitative real-time PCR and digital molecular barcoding
techniques, we assessed total C9ORF72 transcripts, variant 1, variant 2, variant
3, and intron containing transcripts [upstream of the expansion (intron 1a) and
downstream of the expansion (intron 1b)]; the latter were correlated with levels
of poly(GP) and poly(GA) proteins aberrantly translated from the expansion as
measured by immunoassay (n = 50). We detected a decrease in expansion carriers as
compared to controls for total C9ORF72 transcripts, variant 1, and variant 2: the
strongest association was observed for variant 2 (quantitative real-time PCR
cerebellum: median 43 %, p = 1.26e-06, and frontal cortex: median 58 %, p = 1.11e
05; digital molecular barcoding cerebellum: median 31 %, p = 5.23e-10, and
frontal cortex: median 53 %, p = 5.07e-10). Importantly, we revealed that variant
1 levels greater than the 25th percentile conferred a survival advantage [digital
molecular barcoding cerebellum: hazard ratio (HR) 0.31, p = 0.003, and frontal
cortex: HR 0.23, p = 0.0001]. When focusing on intron containing transcripts,
analysis of the frontal cortex revealed an increase of potentially truncated
transcripts in expansion carriers as compared to controls [digital molecular
barcoding frontal cortex (intron 1a): median 272 %, p = 0.003], with the highest
levels in patients pathologically diagnosed with frontotemporal lobar
degeneration. In the cerebellum, our analysis suggested that transcripts were
less likely to be truncated and, excitingly, we discovered that intron containing
transcripts were associated with poly(GP) levels [digital molecular barcoding
cerebellum (intron 1a): r = 0.33, p = 0.02, and (intron 1b): r = 0.49, p =
0.0004] and poly(GA) levels [digital molecular barcoding cerebellum (intron 1a):
r = 0.34, p = 0.02, and (intron 1b): r = 0.38, p = 0.007]. In summary, we report
decreased expression of specific C9ORF72 transcripts and provide support for the
presence of truncated transcripts as well as pre-mRNAs that may serve as
templates for RAN translation. We further show that higher C9ORF72 levels may
have beneficial effects, which warrants caution in the development of new
therapeutic approaches.
PMID- 26437867
TI - Cross-sectional Examination of Long-term Access to Sit-Stand Desks in a
Professional Office Setting.
AB - INTRODUCTION: Prolonged sedentary behavior is an independent risk factor for many
negative health outcomes. Although many employers have begun introducing sit
stand desks as means of reducing employee's occupational sitting time, few
studies have examined the impact of prolonged access to such desks on
sitting/standing time or cardiometabolic outcomes. The present study compared
occupational sedentary/physical activity behaviors and cardiometabolic biomarkers
among employees with long-term access to traditional sitting and sit-stand desks.
METHODS: This study used a naturalistic, cross-sectional study design.
Occupational sedentary and physical activity behaviors and cardiometabolic health
outcomes were collected in a controlled laboratory between February and June
2014. Data were analyzed in September 2014. Adults working in full-time sedentary
desk jobs who reported having either a sit-stand desk (n=31) or standard sitting
desk (n=38) for a minimum of 6 months were recruited. RESULTS: Employees with sit
stand desks sat less (p=0.02) and stood more at work (p=0.01) compared with
employees with sitting desks. Significant inverse correlations were observed
between several occupational physical activity outcomes (walking time, steps at
work) and cardiometabolic risk factors (systolic blood pressure, weight, lean
mass, BMI) over the entire sample. CONCLUSIONS: Employees with long-term access
to sit-stand desks sat less and stood more compared with employees with sitting
desks. These findings hold public health significance, as sit-stand desks
represent a potentially sustainable approach for reducing sedentary behavior
among the large, growing number of sedentary workers at increased risk for
sedentariness-related pathologies.
PMID- 26437868
TI - The Nutrient Content of U.S. Household Food Purchases by Store Type.
AB - INTRODUCTION: Little is known about where households shop for packaged foods,
what foods and beverages they purchase, and the nutrient content of these
purchases. This study describes volume trends and nutrient content (nutrient
profiles, food and beverage groups) of household packaged foods purchases (PFPs)
by store type. METHODS: Cross-sectional analysis of U.S. households' PFPs
(Nielsen Homescan) from 2000 to 2012 (N=652,023 household-year observations) with
survey weights used for national representativeness. Household PFP trends (%
volume), household purchases of key food and beverage groups based on caloric
contribution, and mean caloric and nutrient densities (sugars, saturated fat, and
sodium) of household PFPs were analyzed by store type. Data were collected from
2000 to 2012. Analyses were conducted in 2014-2015. RESULTS: The proportion of
total volume of household PFPs significantly increased from 2000 to 2012 for mass
merchandisers (13.1% to 23.9%), convenience stores (3.6% to 5.9%), and warehouse
clubs (6.2% to 9.8%), and significantly decreased for grocery chains (58.5% to
46.3%) and non-chain grocers (10.3% to 5.2%). Top common sources of calories (%)
from household PFPs by food/beverage group included: savory snacks, grain-based
desserts, and regular soft drinks. The energy, total sugar, sodium, and saturated
fat densities of household PFPs from mass merchandisers, warehouse clubs, and
convenience stores were higher compared with grocery stores. CONCLUSIONS: PFPs
from stores with poorer nutrient density (more energy, total sugar, sodium, and
saturated fat-dense), such as warehouse clubs, mass merchandisers, and
convenience stores are growing, representing a potential U.S. public health
concern.
PMID- 26437869
TI - Association Between Sedentary Work and BMI in a U.S. National Longitudinal
Survey.
AB - INTRODUCTION: Technological advancements have made life and work more sedentary,
and long hours of sitting are known to be associated with many health concerns.
Several studies have reported an association between prolonged sitting time at
work and weight gain, but the results are inconsistent. This study examined the
relationship between sitting time at work and BMI using data from a large
prospective cohort of U.S. men and women from 2002 to 2010. Initial analyses were
performed in 2013, with additional analyses in 2014 and 2015. METHODS: The sample
size at the base year (2002) was 5,285 and the age range 38-45 years. The
outcome, BMI, was based on self-reported measures of height and weight. Estimates
of workplace sitting time were linked from an external database (Occupational
Information Network), and the occupation-wide rating for sitting time was linked
to survey participants by occupation. Fixed-effects models controlling for time
invariant effects of all time-invariant characteristics were employed to examine
the association, controlling for age, education, work hours, and hours of
vigorous and light/moderate physical activities. RESULTS: Longer sitting time was
significantly associated with higher BMI for the overall sample (beta = 0.054;
p<0.05) and men (beta = 0.086; p<0.01). For women, the association was not
statistically significant. CONCLUSIONS: The findings provide further support for
initiatives to reduce workplace sitting time as a means of reducing the risk of
weight gain and related health conditions.
PMID- 26437870
TI - Acidity of two-dimensional zeolites.
AB - Hybrid quantum mechanics:molecular mechanics (QM/MM) calculations of absolute
deprotonation energies are performed with periodic boundary conditions for
Bronsted sites of aluminosilicate bilayers with various Al/Si ratios (two
dimensional zeolite). The supercell method is applied and density functional
theory is used. Much lower values are obtained (1042, 1069 and 1091 kJ mol(-1)
for Al/Si = 1/63, 1/7 and 1/3, respectively) than those for bulk zeolites (1233
kJ mol(-1) for H-chabazite with Al/Si = 1/11). We ascribe the much lower
deprotonation energy to the smaller effective dielectric constant (1.6-1.9) of an
ultra-thin dielectric in a vacuum compared to that of the corresponding bulk
systems (3.0 for H-chabazite), which leads to a better stabilization of the
charge created upon deprotonation.
PMID- 26437871
TI - Efficacy of Azacitidine in De Novo and Relapsed Acute Myeloid Leukemia: A
Retrospective Comparative Study.
AB - INTRODUCTION: Azacitidine is a therapeutic alternative to low-dose cytarabine in
patients with acute myeloid leukemia (AML) who are unfit for intensive
chemotherapy. PATIENTS AND METHODS: We retrospectively analyzed all AML patients
treated with azacitidine at the University Hospital Zurich and the Kantonsspital
Munsterlingen between January 2005 and December 2011. The primary end point was
overall survival (OS). RESULTS: Thirty-eight patients were included in the
analysis. Twenty-one (55%) patients had newly diagnosed AML, 14 (37%) had
relapsed AML, and 3 (8%) underwent bridging therapy before allogeneic stem-cell
transplantation. Age at diagnosis was 72 years in the newly diagnosed cohort and
58 years in the relapsed cohort, 19 (50%) patients were female, 20 (53%) patients
were transfusion dependent, and bone marrow blast count was 43% (interquartile
range, 26-80). Most patients (58%) had poor or very poor risk AML. Patients
received a median (range) of 7 (3-13) therapy cycles. The median (range) OS in
the newly diagnosed and previously treated patient groups were 308 (175-580) days
and 346 (293-628) days, respectively (P = .94). Median OS in the 3 patients
treated before allogeneic stem-cell transplantation has not been reached. Sixty
day mortality was 7.9%, with no difference between the 2 groups. Ongoing or
increasing transfusion dependency was associated with adverse outcome (hazard
ratio, 3.09; 95% confidence interval, 1.29-7.37, P = .011). CONCLUSION: Treatment
with azacitidine led to a median OS of 10 months in both a previously untreated
and a previously treated frail AML patient cohort. A positive effect in
transfusion dependency was observed in 29% of these patients and was associated
with better survival.
PMID- 26437872
TI - Clinical development of RTS,S/AS malaria vaccine: a systematic review of clinical
Phase I-III trials.
AB - The first clinical Phase III trial evaluating a malaria vaccine was completed in
December 2013 at 11 sites from seven sub-Saharan African countries. This
systematic review assesses data of Phase I-III trials including malaria-naive
adults and adults, children and infants from malaria endemic settings in sub
Saharan Africa. The main endpoint of this systematic review was an analysis of
the consistency of efficacy and immunogenicity data from respective Phase I-III
trials. In addition, safety data from a pooled analysis of RTS/AS Phase II trials
and RTS,S/AS01 Phase III trial were reviewed. The RTS,S/AS01 malaria vaccine may
become available on the market in the coming year. If so, further strategies
should address challenges on how to optimize vaccine efficacy and implementation
of RTS,S/AS01 vaccine within the framework of established malaria control
measures.
PMID- 26437873
TI - Femtosecond X-ray absorption study of electron localization in photoexcited
anatase TiO2.
AB - Transition metal oxides are among the most promising solar materials, whose
properties rely on the generation, transport and trapping of charge carriers
(electrons and holes). Identifying the latter's dynamics at room temperature
requires tools that combine elemental and structural sensitivity, with the atomic
scale resolution of time (femtoseconds, fs). Here, we use fs Ti K-edge X-ray
absorption spectroscopy (XAS) upon 3.49 eV (355 nm) excitation of aqueous
colloidal anatase titanium dioxide nanoparticles to probe the trapping dynamics
of photogenerated electrons. We find that their localization at Titanium atoms
occurs in <300 fs, forming Ti(3+) centres, in or near the unit cell where the
electron is created. We conclude that electron localization is due to its
trapping at pentacoordinated sites, mostly present in the surface shell region.
The present demonstration of fs hard X-ray absorption capabilities opens the way
to a detailed description of the charge carrier dynamics in transition metal
oxides.
PMID- 26437874
TI - [The Convention on Biological Diversity and the Nagoya Protocol- Beware of and
prevent their possible side effects on virus research and public health
measures].
PMID- 26437875
TI - Slow intestinal transit contributes to elevate urinary p-cresol level in Italian
autistic children.
AB - The uremic toxin p-cresol (4-methylphenol) is either of environmental origin or
can be synthetized from tyrosine by cresol-producing bacteria present in the gut
lumen. Elevated p-cresol amounts have been previously found in the urines of
Italian and French autism spectrum disorder (ASD) children up until 8 years of
age, and may be associated with autism severity or with the intensity of abnormal
behaviors. This study aims to investigate the mechanism producing elevated
urinary p-cresol in ASD. Urinary p-cresol levels were thus measured by High
Performance Liquid Chromatography in a sample of 53 Italian ASD children assessed
for (a) presence of Clostridium spp. strains in the gut by means of an in vitro
fecal stool test and of Clostridium difficile-derived toxin A/B in the feces, (b)
intestinal permeability using the lactulose/mannitol (LA/MA) test, (c) frequent
use of antibiotics due to recurrent infections during the first 2 years of
postnatal life, and (d) stool habits with the Bristol Stool Form Scale. Chronic
constipation was the only variable significantly associated with total urinary p
cresol concentration (P < 0.05). No association was found with presence of
Clostridium spp. in the gut flora (P = 0.92), augmented intestinal permeability
(P = 0.18), or frequent use of antibiotics in early infancy (P = 0.47). No ASD
child was found to carry C. difficile in the gut or to release toxin A/B in the
feces. In conclusion, urinary p-cresol levels are elevated in young ASD children
with increased intestinal transit time and chronic constipation. Autism Res 2016,
9: 752-759. (c) 2015 International Society for Autism Research, Wiley
Periodicals, Inc.
PMID- 26437876
TI - Special issue on computer-aided drug discovery.
PMID- 26437877
TI - Kinesin-5 is a microtubule polymerase.
AB - Kinesin-5 slides antiparallel microtubules during spindle assembly, and regulates
the branching of growing axons. Besides the mechanical activities enabled by its
tetrameric configuration, the specific motor properties of kinesin-5 that
underlie its cellular function remain unclear. Here by engineering a stable
kinesin-5 dimer and reconstituting microtubule dynamics in vitro, we demonstrate
that kinesin-5 promotes microtubule polymerization by increasing the growth rate
and decreasing the catastrophe frequency. Strikingly, microtubules growing in the
presence of kinesin-5 have curved plus ends, suggesting that the motor stabilizes
growing protofilaments. Single-molecule fluorescence experiments reveal that
kinesin-5 remains bound to the plus ends of static microtubules for 7 s, and
tracks growing microtubule plus ends in a manner dependent on its processivity.
We propose that kinesin-5 pauses at microtubule plus ends and enhances
polymerization by stabilizing longitudinal tubulin-tubulin interactions, and that
these activities underlie the ability kinesin-5 to slide and stabilize
microtubule bundles in cells.
PMID- 26437878
TI - To Transfer or Not to Transfer? Development of a Dinitrosyl Iron Complex as a
Nitroxyl Donor for the Nitroxylation of an Fe(III) -Porphyrin Center.
AB - A positive myocardial inotropic effect achieved using HNO/NO(-) , compared with
NO?, triggered attempts to explore novel nitroxyl donors for use in clinical
applications in vascular and myocardial pharmacology. To develop M-NO complexes
for nitroxyl chemistry and biology, modulation of direct nitroxyl-transfer
reactivity of dinitrosyl iron complexes (DNICs) is investigated in this study
using a Fe(III) -porphyrin complex and proteins as a specific probe. Stable
dinuclear {Fe(NO)2 }(9) DNIC [Fe(MU-(Me) Pyr)(NO)2 ]2 was discovered as a potent
nitroxyl donor for nitroxylation of Fe(III) -heme centers through an associative
mechanism. Beyond the efficient nitroxyl transfer, transformation of DNICs into a
chemical biology probe for nitroxyl and for pharmaceutical applications demands
further efforts using in vitro/in vivo studies.
PMID- 26437879
TI - The effects of phylogenetic relatedness on invasion success and impact:
deconstructing Darwin's naturalisation conundrum.
AB - Darwin's naturalisation conundrum describes the paradox that the relatedness of
exotic species to native residents could either promote or hinder their success
through opposing mechanisms: niche pre-adaptation or competitive interactions.
Previous studies focusing on single snapshots of invasion patterns have provided
support to both sides of the conundrum. Here, by examining invasion dynamics of
480 plots over 40 years, we show that exotic species more closely related to
native species were more likely to enter, establish and dominate the resident
communities, and that native residents more closely related to these successful
exotics were more likely to go locally extinct. Therefore, non-random
displacement of natives during invasion could weaken or even reverse the negative
effects of exotic-native phylogenetic distances on invasion success. The scenario
that exotics more closely related to native residents are more successful, but
tend to eliminate their closely related natives, may help to reconcile the 150
year-old conundrum.
PMID- 26437880
TI - Controlled mud-crack patterning and self-organized cracking of
polydimethylsiloxane elastomer surfaces.
AB - Exploiting pattern formation - such as that observed in nature - in the context
of micro/nanotechnology could have great benefits if coupled with the traditional
top-down lithographic approach. Here, we demonstrate an original and simple
method to produce unique, localized and controllable self-organised patterns on
elastomeric films. A thin, brittle silica-like crust is formed on the surface of
polydimethylsiloxane (PDMS) using oxygen plasma. This crust is subsequently
cracked via the deposition of a thin metal film - having residual tensile stress.
The density of the mud-crack patterns depends on the plasma dose and on the metal
thickness. The mud-crack patterning can be controlled depending on the thickness
and shape of the metallization - ultimately leading to regularly spaced cracks
and/or metal mesa structures. Such patterning of the cracks indicates a level of
self-organization in the structuring and layout of the features - arrived at
simply by imposing metallization boundaries in proximity to each other, separated
by a distance of the order of the critical dimension of the pattern size apparent
in the large surface mud-crack patterns.
PMID- 26437881
TI - Clinical and molecular delineation of dysequilibrium syndrome type 2 and profound
sensorineural hearing loss in an inbred Arab family.
PMID- 26437883
TI - 360 degrees versus localized demarcation laser photocoagulation for macular
sparing retinal detachment in silicone oil-filled eyes with undetected breaks: A
retrospective, comparative, interventional study.
AB - BACKGROUND AND OBJECTIVE: Recurrent retinal detachment (RD) in silicone oil
filled eyes is a serious condition. At the initial stage, it usually spares the
macular and is localized in the inferior retina. The inability to locate the
retinal breaks has been reported to be associated with a poor prognosis and has
limited the use of conventional vitreoretinal surgeries. Demarcation laser
photocoagulation (DLP) is widely accepted for treating macular-sparing RDs. For
laser treatments to be effective, an adequate extent and the correct placement of
the laser is of great importance. The purpose of this research was to compare the
efficacy of 360 degrees and localized DLP in the management of macular-sparing
RD in silicone oil-filled eyes with no detected retinal breaks. MATERIALS AND
METHODS: This is a retrospective, comparative, interventional study. The medical
records of 48 consecutive eyes with macular-sparing RD in silicone oil-filled
eyes with no detected retinal breaks were reviewed. Twenty-six patients (group I)
received 360 degrees DLP, and the remaining 22 patients (group II) underwent
localized DLP. The anatomical and visual outcomes of the two groups were
compared. RESULTS: The mean follow-up period was 12.54 +/- 1.17 months. No
significant difference was identified in the baseline characteristics. The single
operation success rate of 92.31% was achieved in group I, which was significantly
higher than that of group II (59.09%, P = 0.01), and this trend was not weakened
after adjusting for confounding factors (odds ratio: 0.002, P = 0.02). After
salvage management of vitreoretinal surgeries, both groups had equivalent visual
outcomes with silicone oil removal. Multivariate logistic regression also
indicated that the radial extent of RD (odds ratio: 11.10, P = 0.04) was an
independent predictor for laser treatment failure. Significant complications
sufficient to require further operations included proliferative vitreoretinopathy
in two (4.17%) eyes and epiretinal membrane in four (8.33%) eyes. CONCLUSIONS:
The 360 degrees DLP achieved a better primary success rate and equivalent visual
outcomes with localized DLP for macular-sparing RD in silicone oil-filled eyes
with no detected retinal breaks.
PMID- 26437884
TI - Fitness consequences of short- and long-distance pollinations in Phlox hirsuta,
an endangered species.
AB - PREMISE OF THE STUDY: The persistence of rare and endangered plant species may
depend on the distance pollinators travel when dispersing pollen. Pollinations
between adjacent plants, which are often genetically similar, can decrease seed
set, germination, and/or progeny vigor due to shared S-alleles or inbreeding
depression. Interpopulation pollen dispersal is often suggested as a management
tool to increase genetic diversity; however, long-distance pollinations also have
the potential to decrease fitness. METHODS: We performed experimental hand
pollinations in the field and germination experiments in a growth chamber to
determine the effect of intrapopulation pollination distance (1 m, 10 m, and 100
m) on seed set, seed germination, progeny growth, and progeny reproduction in
Phlox hirsuta. In addition, we included interpopulation pollinations (6740 m) to
determine whether artificial gene flow is a viable management option for this
endangered species. KEY RESULTS: Although pollination distance did not affect the
number of healthy seeds produced or the likelihood of radicle emergence, it did
significantly affect the ability of germinating seeds to successfully produce
cotyledons. Outbreeding depression was observed during seed germination and early
seedling development. Seedlings resulting from interpopulation pollinations
developed more slowly and were less likely to survive to produce cotyledons than
seedlings resulting from all three intrapopulation pollination distances.
CONCLUSIONS: Our results suggest that the success of P. hirsuta does not depend
on the distance pollinators travel within populations and that conservation
strategies that involve transporting genes between populations can be
counterproductive.
PMID- 26437882
TI - Targeting mosquito FREP1 with a fungal metabolite blocks malaria transmission.
AB - Inhibiting Plasmodium development in mosquitoes will block malaria transmission.
Fibrinogen-related protein 1 (FREP1) is critical for parasite infection in
Anopheles gambiae and facilitates Plasmodium invasion in mosquitoes through
interacting with gametocytes and ookinetes. To test the hypothesis that small
molecules that disrupt this interaction will prevent parasites from infecting
mosquitoes, we developed an ELISA-based method to screen a fungal extract
library. We obtained a candidate fungal extract of Aspergillus niger that
inhibited the interaction between FREP1 and P. falciparum infected cells by about
92%. The inhibition specificity was confirmed by immunofluorescence assays.
Notably, feeding mosquitoes with the candidate fungal extract significantly
inhibited P. falciparum infection in the midgut without cytotoxicity or
inhibition of the development of P. falciparum gametocytes or ookinetes. A
bioactive natural product that prevents FREP1 from binding to gametocytes or
ookinetes was isolated and identified as P-orlandin. Importantly, the nontoxic
orlandin significantly reduced P. falciparum infection intensity in mosquitoes.
Therefore, disruption of the interaction between FREP1 and parasites effectively
reduces Plasmodium infection in mosquitoes. Targeting FREP1 with small molecules
is thus an effective novel approach to block malaria transmission.
PMID- 26437885
TI - Pleistocene climatic oscillations rather than recent human disturbance influence
genetic diversity in one of the world's highest treeline species.
AB - PREMISE OF THE STUDY: Biological responses to climatic change usually leave
imprints on the genetic diversity and structure of plants. Information on the
current genetic diversity and structure of dominant tree species has facilitated
our general understanding of phylogeographical patterns. METHODS: Using amplified
fragment length polymorphism (AFLPs), we compared genetic diversity and structure
of 384 adults of P. tarapacana with those of 384 seedlings across 32 forest sites
spanning a latitudinal gradient of 600 km occurring between 4100 m and 5000 m
a.s.l. in Polylepis tarapacana (Rosaceae), one of the world's highest treeline
species endemic to the central Andes. KEY RESULTS: Moderate to high levels of
genetic diversity and low genetic differentiation were detected in both adults
and seedlings, with levels of genetic diversity and differentiation being almost
identical. Four slightly genetically divergent clusters were identified that
accorded to differing geographical regions. Genetic diversity decreased from
south to north and with increasing precipitation for adults and seedlings, but
there was no relationship to elevation. CONCLUSIONS: Our study shows that, unlike
the case for other Andean treeline species, recent human activities have not
affected the genetic structure of P. tarapacana, possibly because its
inhospitable habitat is unsuitable for agriculture. The current genetic pattern
of P. tarapacana points to a historically more widespread distribution at lower
altitudes, which allowed considerable gene flow possibly during the glacial
periods of the Pleistocene epoch, and also suggests that the northern Argentinean
Andes may have served as a refugium for historical populations.
PMID- 26437886
TI - Functional and environmental determinants of bark thickness in fire-free
temperate rain forest communities.
AB - PREMISE OF THE STUDY: In fire-prone ecosystems, variation in bark thickness among
species and communities has been explained by fire frequency; thick bark is
necessary to protect cambium from lethal temperatures. Elsewhere this investment
is deemed unnecessary, and thin bark is thought to prevail. However, in rain
forest ecosystems where fire is rare, bark thickness varies widely among species
and communities, and the causes of this variation remain enigmatic. We tested for
functional explanations of bark thickness variation in temperate rain forest
species and communities. METHODS: We measured bark thickness in 82 tree species
throughout New Zealand temperate rain forests that historically have experienced
little fire and applied two complementary analyses. First, we examined
correlations between bark traits and leaf habit, and leaf and stem traits.
Second, we calculated community-weighted mean (CWM) bark thickness for 272 plots
distributed throughout New Zealand to identify the environments in which thicker
barked communities occur. KEY RESULTS: Conifers had higher size-independent bark
thickness than evergreen angiosperms. Species with thicker bark or higher bark
allocation coefficients were not associated with "slow economic" plant traits.
Across 272 forest plots, communities with thicker bark occurred on infertile
soils, and communities with thicker bark and higher bark allocation coefficients
occurred in cooler, drier climates. CONCLUSIONS: In non-fire-prone temperate rain
forest ecosystems, investment in bark is driven by soil resources, cool minimum
temperatures, and seasonal moisture stress. The role of these factors in fire
prone ecosystems warrants testing.
PMID- 26437887
TI - Vicariance, long-distance dispersal, and regional extinction-recolonization
dynamics explain the disjunct circumpolar distribution of the arctic-alpine plant
Silene acaulis.
AB - PREMISE OF THE STUDY: Many arctic-alpine species have vast geographic ranges, but
these may encompass substantial gaps whose origins are poorly understood. Here we
address the phylogeographic history of Silene acaulis, a perennial cushion plant
with a circumpolar distribution except for a large gap in Siberia. METHODS: We
assessed genetic variation in a range-wide sample of 103 populations using
plastid DNA (pDNA) sequences and AFLPs (amplified fragment length polymorphisms).
We constructed a haplotype network and performed Bayesian phylogenetic analyses
based on plastid sequences. We visualized AFLP patterns using principal
coordinate analysis, identified genetic groups using the program structure, and
estimated genetic diversity and rarity indices by geographic region. KEY RESULTS:
The history of the main pDNA lineages was estimated to span several glaciations.
AFLP data revealed a distinct division between Beringia/North America and
Europe/East Greenland. These two regions shared only one of 17 pDNA haplotypes.
Populations on opposite sides of the Siberian range gap (Ural Mountains and
Chukotka) were genetically distinct and appear to have resulted from postglacial
leading-edge colonizations. We inferred two refugia in North America (Beringia
and the southern Rocky Mountains) and two in Europe (central-southern Europe and
northern Europe/East Greenland). Patterns in the East Atlantic region suggested
transoceanic long-distance dispersal events. CONCLUSIONS: Silene acaulis has a
highly dynamic history characterized by vicariance, regional extinction, and
recolonization, with persistence in at least four refugia. Long-distance
dispersal explains patterns across the Atlantic Ocean, but we found no evidence
of dispersal across the Siberian range gap.
PMID- 26437888
TI - Ploidy and domestication are associated with genome size variation in Palms.
AB - PREMISE OF THE STUDY: The genome size of a species (C-value) is associated with
growth, development and adaptation to environmental changes. Angiosperm C-values
range 1200-fold and frequently vary within species, although little is known
about the impacts of domestication on genome size. Genome size variation among
related species of palms is of evolutionary significance because changes
characterize clades and may be associated with polyploidy, transposon
amplifications, deletions, or rearrangements. Further knowledge of genome size
will provide crucial information needed for planning of whole genome sequencing
and accurate annotations. We studied the genome size of Cocos nucifera and its
variation among cultivars, and compared it to values for related palms from the
Attaleinae subtribe. METHODS: Flow cytometric analysis of isolated nuclei from
young palm leaves was used to estimate genome sizes of 23 coconut cultivars
(Talls, Dwarfs, and hybrids) worldwide and 17 Cocoseae species. Ancestral genome
size was reconstructed on a maximum likelihood phylogeny of Attaleinae from seven
WRKY loci. KEY RESULTS: The coconut genome is large-averaging 5.966 pg-and shows
intraspecific variation associated with domestication. Variation among Tall
coconuts was significantly greater than among Dwarfs. Attaleinae genomes showed
moderate size variation across genera, except polyploids Jubaeopsis caffra,
Voanioala gerardii, Beccariophoenix alfredii, and Allagoptera caudescens, which
had larger genomes. CONCLUSIONS: Our results contribute to the understanding of
the relationship between domestication and genome size in long-lived tree crops
and provide a basis for whole-genome sequencing of the coconut and other
domesticated plants. Polyploidy evolved independently in two clades within
Attaleinae.
PMID- 26437889
TI - Structural Characterization of Sm(III)(EDTMP).
AB - Samarium-153 ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid)
((153)Sm-EDTMP, or samarium lexidronam), also known by its registered trademark
name Quadramet, is an approved therapeutic radiopharmaceutical used in the
palliative treatment of painful bone metastases. Typically, patients with
prostate, breast, or lung cancer are most likely to go on to require bone pain
palliation treatment due to bone metastases. Sm(EDTMP) is a bone-seeking drug
which accumulates on rapidly growing bone, thereby delivering a highly region
specific dose of radiation, chiefly through beta particle emission. Even with its
widespread clinical use, the structure of Sm(EDTMP) has not yet been
characterized at atomic resolution, despite attempts to crystallize the complex.
Herein, we prepared a 1:1 complex of the cold (stable isotope) of Sm(EDTMP) under
alkaline conditions and then isolated and characterized the complex using
conventional spectroscopic techniques, as well as with extended X-ray absorption
fine structure (EXAFS) spectroscopy and density functional structure
calculations, using natural abundance Sm. We present the atomic resolution
structure of [Sm(III)(EDTMP)-8H](5-) for the first time, supported by the EXAFS
data and complementary spectroscopic techniques, which demonstrate that the
samarium coordination environment in solution is in agreement with the structure
that has long been conjectured.
PMID- 26437890
TI - Implementation of High-Quality Warm-White Light-Emitting Diodes by a Model
Experimental Feedback Approach Using Quantum Dot-Salt Mixed Crystals.
AB - In this work, a model-experimental feedback approach is developed and applied to
fabricate high-quality, warm-white light-emitting diodes based on quantum dots
(QDs) as color-conversion materials. Owing to their unique chemical and physical
properties, QDs offer huge potential for lighting applications. Nevertheless,
both emission stability and processability of the QDs are limited upon usage from
solution. Incorporating them into a solid ionic matrix overcomes both of these
drawbacks, while preserving the initial optical properties. Here borax
(Na2B4O7.10H2O) is used as a host matrix because of its lower solubility and
thereby reduced ionic strength in water in comparison with NaCl. This guarantees
the stability of high-quality CdSe/ZnS QDs in the aqueous phase during
crystallization and results in a 3.4 times higher loading amount of QDs within
the borax crystals compared to NaCl. All steps from the synthesis via mixed
crystal preparation to the warm-white LED preparation are verified by applying
the model-experimental feedback, in which experimental data and numerical results
provide feedback to each other recursively. These measures are taken to ensure a
high luminous efficacy of optical radiation (LER) and a high color rendering
index (CRI) of the final device as well as a correlated color temperature (CCT)
comparable to an incandescent bulb. By doing so, a warm-white LED with a LER of
341 lm/Wopt, a CCT of 2720 K and a CRI of 91.1 is produced. Finally, we show that
the emission stability of the QDs within the borax crystals on LEDs driven at
high currents is significantly improved. These findings indicate that the
proposed warm-white light-emitting diodes based on QDs-in-borax hold great
promise for quality lighting.
PMID- 26437891
TI - Coronary artery perforation: don't rush, IVUS may be useful.
AB - Coronary artery perforation (CAP) is a rare but potentially fatal complication of
percutaneous coronary intervention. Polytetrafluoroethylene-covered stents
prevent blood leakage between struts with a high rate of success. However, they
lack elasticity and rapid and correct deployment is difficult. They have also a
higher rate of stent restenosis and thrombosis. For these reasons, optimal
deployment is essential. Although severe CAP needs an emergent solution, after
stabilizing the patient, intracoronary imaging techniques may be useful to ensure
correct expansion and reduce further adverse events. We present a case that shows
the potential role of intravascular ultrasound in the resolution of a CAP.
PMID- 26437893
TI - Preoperative neutrophil to lymphocyte ratio predicts survival in patients with T1
2N0 colorectal cancer.
AB - PURPOSE: Neutrophil to lymphocyte ratio (NLR) is reported to be associated with
prognosis of colorectal cancer. The aim of this study is to determine whether the
NLR is a predictor of oncological outcomes in patients with stage I colorectal
cancer who underwent curative surgery. METHODS: Two hundred sixty-nine patients
with stage I colorectal cancer who underwent surgical resection between December
2003 and December 2011 were retrospectively reviewed. The cutoff for NLR was
defined as three by maximizing log-rank test statistics. We compared patients
with a low NLR and those with a high NLR in terms of survival. RESULTS: The 5
year disease-free survival (DFS) and cancer-specific survival (CSS) rates were
lower in patients with a high NLR compared to those with a low NLR in stage I
colorectal cancer (89.5% vs. 97.4%, P = 0.006; 94.0% vs. 98.9%, P = 0.022). Cox
multivariate analysis demonstrated that preoperative NLR was independently
associated with DFS (HR, 5.216; 95%CI, 1.400-19.431; P = 0.014) and CSS (HR,
6.190; 95%CI, 1.034-37.047; P = 0.046) in patients with stage I colorectal
cancer. CONCLUSION: The preoperative NLR is a prognostic factor predicting DFS
and CSS in patients with stage I colorectal cancer who underwent curative
surgery.
PMID- 26437892
TI - Effects of prenatal inhalation exposure to copper nanoparticles on murine dams
and offspring.
AB - BACKGROUND: Increasing numbers of individuals may be exposed to nanomaterials
during pregnancy. The overarching goal of this investigation was to determine if
prenatal inhalation exposure to copper nanoparticles (Cu NPs) has an effect on
dams and offspring, including an analysis of inflammatory markers (Th1/Th2
cytokine profiles). METHODS: Physicochemical characterization of Cu NPs was
performed. Pregnant and non-pregnant mice (C57Bl/6 J) were exposed to Cu NPs or
laboratory air in the whole-body chamber for 4 hrs/day on gestation days (GD) 3
19 (3.5 mg/m(3)). Animals were euthanized on GD 19 (0 week) or 7 weeks later.
Bronchoalveolar lavage (BAL) fluid was analyzed for total and differential cells.
Cytokine/chemokine concentrations were determined in the BAL fluid and the plasma
of dams/non-pregnant mice and pups. Cu content was determined in the lungs and
the blood of dams/non-pregnant mice and pups, in the placentas as well as in the
whole bodies of pups immediately after delivery. Lungs and placentas were
evaluated for histopathological changes. Gene expression of the Th1/Th2 profiles
were analyzed in spleens of pups. RESULTS: The survival rate of 7 week old pups
exposed to Cu NPs was significantly lower than control pups (73 vs. 97 %). The
average litter size, male/female ratio, body weight and lenght at birth were not
different between Cu NP-exposed and control mice. Both pregnant and non-pregnant
mice exposed to Cu NPs had significant pulmonary inflammation with increased
number of neutrophils in the BAL fluid compared to controls. Perivascular
lymphoplasmacytic cuffing was found in the lungs of exposed mice and was more
pronounced in the non-pregnant group. Similarly, levels of inflammatory
cytokines/chemokines IL-12(p40), G-CSF, GM-CSF, KC, MCP-1, MIP-1alpha, MIP-1beta,
RANTES and TNF-alpha in BAL fluid were significantly higher in non-pregnant than
pregnant exposed mice. Histopathology evaluation of placentas did not identify
any pathological changes. No translocation of Cu into the placenta or the fetus
was found by inductively coupled plasma-mass spectroscopy. Expression of several
Th1/Th2 or other immune response genes in pups' spleens were found to be
significantly up- or down-regulated. CONCLUSIONS: Prenatal exposure to Cu NPs
caused a profound pulmonary inflammation in dams and strong immunomodulatory
effects in offspring. There was no clear polarization of genes expressed in pups'
spleens towards Th1 or Th2 type of response.
PMID- 26437895
TI - Embodied simulation of emotional valence: Facial muscle responses to abstract and
concrete words.
AB - Semantic knowledge is thought to be at least partially grounded in sensory,
motor, and affective information, acquired through experiences in our inner and
outer world. The reactivation of experience-related information during meaning
access is called simulation. In the affective simulation account, it is assumed
that the grounding information depends on the concepts' concreteness. Whereas
abstract concepts are thought to be mainly represented through affective
experiential information, concrete words rely more on sensory-motor experiential
information. To test this hypothesis, we measured facial muscle activity as an
indicator of affective simulation during visual word recognition. Words varied on
the dimensions of concreteness and valence. Behavioral and electromyographic data
were analyzed with linear mixed-effects models with maximal random effect
structure to optimize generalization over participants and word samples. Contrary
to this hypothesis, we found a valence effect in the m. corrugator supercilii
only in response to concrete but not to abstract words. Our data show that
affective simulation as measured with facial muscle activity occurs in response
to concrete rather than to abstract words. More concrete words are supposed to
have higher context availability and richer visual imagery, which might promote
affective simulation on the expressive level of facial muscle activity. The
results are in line with embodied accounts of semantic representation but speak
against its predominant role for representing affective information in abstract
concepts.
PMID- 26437894
TI - A potential role for interleukin-33 and gamma-epithelium sodium channel in the
pathogenesis of human malaria associated lung injury.
AB - BACKGROUND: The pathogenesis of pulmonary oedema (PE) in patients with severe
malaria is still unclear. It has been hypothesized that lung injury depends, in
addition to microvascular obstruction, on an increased pulmonary capillary
pressure and altered alveolar-capillary membrane permeability, causing pulmonary
fluid accumulation. METHODS: This study compared the histopathological features
of lung injury in Southeast Asian patients (n = 43) who died from severe
Plasmodium falciparum malaria, and correlated these with clinical history in
groups with or without PE. To investigate the expression of mediators that may
influence fluid accumulation in PE, immunohistochemistry and image analysis were
performed on controls and sub-sets of patient with or without PE. RESULTS: The
expression of leukocyte sub-set antigens, bronchial interleukin (IL)-33, gamma
epithelium sodium channel (ENaC), aquaporin (AQP)-1 and -5, and control
cytokeratin staining was quantified in the lung tissue of severe malaria
patients. Bronchial IL-33 expression was significantly increased in severe
malaria patients with PE. Malaria patients with shock showed significantly
increased bronchial IL-33 compare to other clinical manifestations. Bronchial IL
33 levels were positively correlated with CD68+ monocyte and elastase +
neutrophil, septal congestion and hyaline membrane formation. Moreover, the
expression of both vascular smooth muscle cell (VSMC) and bronchial gamma-ENaC
significantly decreased in severe malaria patients with PE. Both VSMC and
bronchial gamma-ENaC were negatively correlated with the degree of parasitized
erythrocyte sequestration, alveolar thickness, alveolar expansion score, septal
congestion score, and malarial pigment score. In contrast AQP-1 and -5 and pan
cytokeratin levels were similar between groups. CONCLUSIONS: The results suggest
that IL-33 may play a role in lung injury during severe malaria and lead to PE.
Both VSMC and bronchial gamma-ENaC downregulation may explain pulmonary fluid
disturbances and participate in PE pathogenesis in severe malaria patients.
PMID- 26437896
TI - A facile method of activating graphitic carbon nitride for enhanced
photocatalytic activity.
AB - Activated graphitic carbon nitride (g-C3N4) with enhanced photocatalytic
capability under visible light irradiation was fabricated by using a facile
chemical activation treatment method. In the chemical activation, a mixed
solution of hydrogen peroxide and ammonia was employed. The yield can reach as
high as 90% after the activation process. The activation process did not change
the crystal structure, functional group, morphology and specific surface area of
pristine g-C3N4, but it introduced H and O elements into the CN framework of g
C3N4, resulting in a broader optical absorption range, higher light absorption
capability and more efficient separation of photogenerated electrons and holes.
The photoactivity was investigated by the degradation of rhodamine B (RhB) under
visible light irradiation. As compared to the pristine g-C3N4, the activated g
C3N4 exhibited a distinct and efficient two-step degradation process. It was
found that the RhB dye in the activated g-C3N4 was mainly oxidized by the
photogenerated holes. It is believed that sufficient holes account for the two
step degradation process because they would significantly improve the efficiency
of the N-de-ethylation reaction of RhB.
PMID- 26437897
TI - Lipid droplets and associated proteins in the skin: basic research and clinical
perspectives.
AB - Lipid droplets (LDs), the major organelles handling fat storage, comprise a
hydrophobic neutral lipid core surrounded by a phospholipid monolayer embedded
with a protein miscellany. Although lipids of the stratum corneum are essential
for the skin barrier, and progressive lipid accumulation culminating in cell
disruption is the hallmark of sebaceous differentiation, only a few studies
touched on skin LD and associated proteins so far. Here, after briefly
introducing the basic facts about LD and associated proteins, we discuss how
forthcoming studies may unveil novel players in skin lipid metabolism and
candidate target proteins for treating skin diseases.
PMID- 26437898
TI - Cone-beam evaluation of pharyngeal airway space in class I, II, and III patients.
AB - OBJECTIVES: The purpose of this study is to make a 3-dimensional (3-D) evaluation
of the pharyngeal airway space (PAS) in patients with class I, II, and III
malocclusion. STUDY DESIGN: Sixty patients were evaluated. The patients were
divided in 3 groups according to their occlusion classification. The volume and
area of PAS were evaluated using the software Dolphin 3-D Imaging in the
preoperative period for orthognathic surgery. RESULTS: PAS volume and area were
influenced by different patterns of malocclusion. The mean volume and area for
class III patients were statistically bigger than for classes I and II patients
(P < .001). There was also a significant difference for volume values between
class I and II patients, being the bigger volume for the class I patients (P <
.05). CONCLUSIONS: It was possible to conclude that the class III patients
presented a bigger PAS compared with classes I and II patients.
PMID- 26437899
TI - Correlation of deglutition in subacute ischemic stroke patients with peripheral
blood adaptive immunity: Essential amino acid improvement.
AB - We aimed to document in stroke patients peripheral blood immune cell profiles,
their relations with neuro-functional tests, and any possible influence of
supplemented essential amino acids (EAAs) may have on both the immune system and
the relationship of the latter with neuro-function.Forty-two dysphagic stroke
patients (27 men; 71+/-9 years) underwent bio-humoral measurements, neuro
functional tests, including Functional Independence Measure (FIM) and Dysphagia
Outcome and Severity Scale (DOSS), and were randomized to receive EAAs 8 g/d (EAA
group) or isocaloric maltodextrin (placebo group).At discharge all measurements
were repeated 38+/-1 days after randomization.At admission, total white cell
(TWC), neutrophil (N), and lymphocyte (Lymph) counts were normal and the N/Lymph
ratio was higher than normal values (<3.0). At discharge, both TWC and N
decreased while Lymph increased significantly. As a result, the N/Lymph ratio
significantly decreased (P <0.001) returning to normal levels. Absolute Lymph
counts and Lymph % TWC correlated positively with DOSS (r = +0.235, P = 0.04 and
r = +0.224, P = 0.05, respectively), negatively with C-reactive protein natural
logarithm (ln CRP) (P = 0.02 and P = 0.0001, respectively), which is an
inflammation marker. N correlated positively with ln CRP (P = 0.001) and had a
slight negative association with FIM (P = 0.07). The N/Lymph ratio was inversely
related to FIM (r = -0.262, P = 0.02) and DOSS (r = -0.279, P = 0.01). Finally,
FIM correlated with DOSS (r = +0.35, P = 0.05).For the regression analysis, the
overtime changes of Lymph % TWC correlated significantly with DOSS (P = 0.01).
There was a positive correlation between Lymph % TWC and DOSS for the entire
stroke population (P = 0.015). While this correlation was not important for the
placebo group (P = 0.27), it was significant in the EAA subgroup (P = 0.018).In
the sub-acute stroke stage, there may be slight alterations of peripheral blood
immune cells. Lymph cells are associated with improved neuro-function tests with
evidence that this association is enhanced by supplementing EAAs.
PMID- 26437900
TI - Metallic Co4N Porous Nanowire Arrays Activated by Surface Oxidation as
Electrocatalysts for the Oxygen Evolution Reaction.
AB - Designing highly efficient electrocatalysts for oxygen evolution reaction (OER)
plays a key role in the development of various renewable energy storage and
conversion devices. In this work, we developed metallic Co4N porous nanowire
arrays directly grown on flexible substrates as highly active OER
electrocatalysts for the first time. Benefiting from the collaborative advantages
of metallic character, 1D porous nanowire arrays, and unique 3D electrode
configuration, surface oxidation activated Co4N porous nanowire arrays/carbon
cloth achieved an extremely small overpotential of 257 mV at a current density of
10 mA cm(-2), and a low Tafel slope of 44 mV dec(-1) in an alkaline medium, which
is the best OER performance among reported Co-based electrocatalysts to date.
Moreover, in-depth mechanistic investigations demonstrate the active phases are
the metallic Co4N core inside with a thin cobalt oxides/hydroxides shell during
the OER process. Our finding introduces a new concept to explore the design of
high-efficiency OER electrocatalysts.
PMID- 26437901
TI - Molecular essence and endocrine responsiveness of estrogen receptor-negative,
progesterone receptor-positive, and HER2-negative breast cancer.
AB - BACKGROUND: The clinical significance of progesterone receptor (PgR) expression
in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we
systemically investigate the clinicopathologic features, molecular essence, and
endocrine responsiveness of ER-/PgR+/HER2- phenotype. METHODS: Four study cohorts
were included. The first and second cohorts were from the Surveillance,
Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai
Cancer Center (n = 2,338), respectively, for clinicopathologic and survival
analysis. The third and fourth cohorts were from two independent publicly
available microarray datasets including 837 operable cases and 483 cases
undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene
expression analysis. Characterized genes defining subgroups within the ER
/PgR+/HER2- phenotype were determined and further validated. RESULTS:
Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell
in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR
. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled
by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a
fixed-effects method) were basal-like. We further refined the characterized genes
for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry
based method that could determine the molecular essence of ER-/PgR+ using three
markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry
defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity
score compared with luminal-like ER-/PgR+ cases (P <0.0001 by Mann-Whitney test
for each study set and P <0.0001 for pooled standardized mean difference in meta
analysis). Immunohistochemistry-defined basal-like ER-/PgR+ cases might not
benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus
insufficient endocrine therapy). CONCLUSIONS: The majority of ER-/PgR+/HER2-
phenotype breast cancers are basal-like and associated with a lower endocrine
therapy sensitivity score. Additional studies are needed to validate these
findings.
PMID- 26437903
TI - The multicomponent meningococcal serogroup B vaccine (4CMenB): origin,
composition, health impact and unknown aspects.
AB - Neisseria meningitidis serogroup B is the main cause for meningococcal invasive
disease in many parts of the world. Since 2013, a new multicomponent vaccine
against meningococcal serogroup B (4CMenB) has been licensed in Europe,
Australia, Canada, Chile, Uruguay, USA and Brazil with different immunization
schedules. Clinical trials involving adults, adolescents, children and infants
showed 4CMenB has a good immunogenicity and safety profile. Strain coverage
estimates are similar to or better than other recently approved vaccines, ranging
from 66% in Canada to 91% in Unites States. Some points still remain to be
clarified such as the best immunization strategy, the effect of 4CMenB on
carriage, the long-term persistence of protective bactericidal antibodies titers,
long-term safety outcomes, the possible emergence of N. meningitidis escape
mutants and the vaccine cost-effectiveness. In this review, we focus on the
vaccine composition, clinical trials and suggested schedules, safety data,
potential strain coverage and future challenges.
PMID- 26437902
TI - Phylum-wide analysis of genes/proteins related to the last steps of assembly and
export of extracellular polymeric substances (EPS) in cyanobacteria.
AB - Many cyanobacteria produce extracellular polymeric substances (EPS) with
particular characteristics (e.g. anionic nature and presence of sulfate) that
make them suitable for industrial processes such as bioremediation of heavy
metals or thickening, suspending or emulsifying agents. Nevertheless, their
biosynthetic pathway(s) are still largely unknown, limiting their utilization. In
this work, a phylum-wide analysis of genes/proteins putatively involved in the
assembly and export of EPS in cyanobacteria was performed. Our results
demonstrated that most strains harbor genes encoding proteins related to the
three main pathways: Wzy-, ABC transporter-, and Synthase-dependent, but often
not the complete set defining one pathway. Multiple gene copies are mainly
correlated to larger genomes, and the strains with reduced genomes (e.g. the
clade of marine unicellular Synechococcus and Prochlorococcus), seem to have lost
most of the EPS-related genes. Overall, the distribution of the different
genes/proteins within the cyanobacteria phylum raises the hypothesis that
cyanobacterial EPS production may not strictly follow one of the pathways
previously characterized. Moreover, for the proteins involved in EPS
polymerization, amino acid patterns were defined and validated constituting a
novel and robust tool to identify proteins with similar functions and giving a
first insight to which polymer biosynthesis they are related to.
PMID- 26437904
TI - Does the Rewarmed Heart Restore the Myocardial Proteome to That of the Pre-Cooled
State?--A Proteomic Analysis of Surgical Samples.
AB - BACKGROUND: Hypothermia is utilized in cardiac and aortic surgery to protect
organs from ischemic reperfusion injury. Although the cooled body is invariably
rewarmed after the procedure, it is still unknown whether the rewarmed body
regains its former biological state. This study determined the modulatory effects
of hypothermia on the human myocardial proteome and whether subsequent rewarming
restores the proteome to the state prior to cooling. METHODS AND RESULTS: A
quantitative proteomic analysis was performed using isobaric tags for relative
and absolute quantification labeling tandem mass spectrometry. Right atrial
samples were taken 3 times (pre, during and post cooling) during deep hypothermic
cardiopulmonary bypass (CPB) from 8 patients with aortic arch aneurysms and 3
corresponding time points during normothermic CPB from 8 patients with ascending
aortic or valsalva aneurysms. In total, 697 proteins were identified, with 222
proteins having high protein confidence. Bioinformatic analyses revealed
significant downregulation of 19 proteins associated with energy production at
hypothermic cardioplegic arrest. On rewarmed beating, 10 proteins remained
downregulated, including those regulating cardiac contraction and adaptor
proteins, although levels of the aforementioned 19 downregulated proteins
returned to their initial values. Additional echocardiographic evaluation
demonstrated that hypothermia preserved the variables of diastolic function to a
greater extent than normothermic surgery. CONCLUSIONS: Rewarming restores the
human myocardial proteome to the pre-cooled state, except for proteins regulating
cardiac contraction and adaptor proteins.
PMID- 26437905
TI - Recent progress and next challenges in the treatment of symptomatic heart failure
in Japan.
PMID- 26437906
TI - Long-term outcomes after St. Jude Medical mechanical valve implantation.
PMID- 26437908
TI - How often does the embryo implant at the location to which it was transferred?
AB - OBJECTIVE: To determine how often the embryo implants exactly at the site of
transfer and what additional factors may affect the eventual site of implantation
in assisted reproductive technology (ART) cycles. METHODS: This was a prospective
observational study of women undergoing ART treatment in a tertiary university
unit. Several factors inherent to the embryo transfer (ET), such as the location
of the air bubbles and uterine contractility at 1 and at 60 min after ET were
assessed with two-dimensional and three-dimensional (3D) ultrasound. In women in
whom there was a resulting pregnancy, the position of the gestational sac (i.e.
right, left, center or low) was subsequently assessed using 3D ultrasound, and
predictors of its location were evaluated. RESULTS: Of 239 recruited women with
visualization of air bubbles at ET, 71 singleton gestational sacs were
subsequently observed on 3D ultrasound. Overall, 40.8% (29/71) of embryos
implanted at the location where the air bubbles were visualized at 1 min after
ET, and 50.7% (36/71) implanted where the air bubbles were visualized at 60 min
after ET (Cohen's kappa coefficients 0.21 and 0.37, respectively; comparison of
agreement values: P = 0.28). Specifically, at 1 min the correspondence between
the location of the air bubble and embryo implantation was 37.5% (6/16), 57.1%
(8/14), 36.8% (7/19) and 36.4% (8/22) for right, left, central and lower uterus,
respectively (4 * 4 contingency table, P < 0.01); at 60 min, the correspondence
was 72.2% (13/18), 50.0% (9/18), 33.3% (8/24) and 85.7% (6/7), respectively (5 *
4 contingency table, P < 0.001). In addition, higher vs lower frequency of
uterine contractions at 60 min was associated with different sites of
implantation (5.6% (1/18), 11.1% (2/18), 27.8% (5/18) and 55.6% (10/18) vs 34.0%
(18/53), 24.5% (13/53), 13.2% (7/53) and 28.3% (15/53) for right, left, central
and lower uterus, respectively, P < 0.05). In particular, a high uterine
contraction frequency following ET was associated with a twofold increased chance
of the pregnancy implanting in the lower part of the uterine cavity (relative
risk, 1.96 (95% CI, 1.08-3.56), P < 0.05). CONCLUSIONS: The position of the air
bubbles within the first 60 min of ET appears to predict the site of implantation
in approximately half of cases, denoting an overall poor agreement. This implies
significant embryo migration, and has important clinical implications, as it
demonstrates that other factors such as uterine contractility may dictate where
the embryo will eventually implant following transfer. Copyright (c) 2015 ISUOG.
Published by John Wiley & Sons Ltd.
PMID- 26437907
TI - Autism screening and diagnosis in low resource settings: Challenges and
opportunities to enhance research and services worldwide.
AB - Most research into the epidemiology, etiology, clinical manifestations, diagnosis
and treatment of autism is based on studies in high income countries. Moreover,
within high income countries, individuals of high socioeconomic status are
disproportionately represented among participants in autism research.
Corresponding disparities in access to autism screening, diagnosis, and treatment
exist globally. One of the barriers perpetuating this imbalance is the high cost
of proprietary tools for diagnosing autism and for delivering evidence-based
therapies. Another barrier is the high cost of training of professionals and para
professionals to use the tools. Open-source and open access models provide a way
to facilitate global collaboration and training. Using these models and
technologies, the autism scientific community and clinicians worldwide should be
able to work more effectively and efficiently than they have to date to address
the global imbalance in autism knowledge and at the same time advance our
understanding of autism and our ability to deliver cost-effective services to
everyone in need.
PMID- 26437909
TI - Utilization of Systemic Chemotherapy in Advanced Urothelial Cancer: A
Retrospective Collaborative Study by the Hellenic Genitourinary Cancer Group
(HGUCG).
AB - BACKGROUND: Advanced urothelial cancer (AUCa) is associated with poor long-term
survival. Two major concerns are related to nonexposure to cisplatin-based
chemotherapy and poor outcome after relapse. Our purpose was to record patterns
of practice in AUCa in Greece, focusing on first-line treatment and management of
relapsed disease. METHODS: Patients with AUCa treated from 2011 to 2013 were
included in the analysis. Fitness for cisplatin was assessed by recently
established criteria. RESULTS: Of 327 patients treated with first-line
chemotherapy, 179 (55%) did not receive cisplatin. Criteria for unfitness for
cisplatin were: Eastern Cooperative Oncology Group (ECOG) performance status (PS)
>= 2, 21%; creatinine clearance <= 60 mL/min, 55%; hearing impairment, 8%;
neuropathy, 1%; and cardiac failure, 5%. Forty-six patients (27%) did not fulfill
any criterion for unfitness for cisplatin. The main reasons for these deviations
were comorbidities (28%) and advanced age (32%). Seventy-four (68%) of 109
patients who experienced a relapse received second-line chemotherapy. The most
frequent reason for not offering second-line chemotherapy was poor PS or limited
life expectancy (66%). CONCLUSION: In line with international data, approximately
50% of Greek patients with AUCa do not receive cisplatin-based chemotherapy,
although 27% of them were suitable for such treatment. In addition, about one
third of patients with relapse did not receive second-line chemotherapy because
of poor PS or short life expectancy. Enforcing criteria for fitness for cisplatin
and earlier diagnosis of relapse represent 2 targets for improvement in current
treatment practice for AUCa.
PMID- 26437912
TI - Pd(II)-Catalyzed C-H Activation of Styrylindoles: Short, Efficient, and
Regioselective Synthesis of Functionalized Carbazoles.
AB - A novel Pd(II)-catalyzed approach for the direct synthesis of highly
functionalized carbazoles from unprotected styrylindoles has been developed. The
reaction features a variety of olefin substrates, which are readily switchable by
subtle tuning of the reaction conditions. Investigations of the mechanism suggest
that the C-H activation proceeds via enamine formation.
PMID- 26437911
TI - Measuring fast stochastic displacements of bio-membranes with dynamic optical
displacement spectroscopy.
AB - Stochastic displacements or fluctuations of biological membranes are increasingly
recognized as an important aspect of many physiological processes, but hitherto
their precise quantification in living cells was limited due to a lack of tools
to accurately record them. Here we introduce a novel technique--dynamic optical
displacement spectroscopy (DODS), to measure stochastic displacements of
membranes with unprecedented combined spatiotemporal resolution of 20 nm and 10
MUs. The technique was validated by measuring bending fluctuations of model
membranes. DODS was then used to explore the fluctuations in human red blood
cells, which showed an ATP-induced enhancement of non-Gaussian behaviour. Plasma
membrane fluctuations of human macrophages were quantified to this accuracy for
the first time. Stimulation with a cytokine enhanced non-Gaussian contributions
to these fluctuations. Simplicity of implementation, and high accuracy make DODS
a promising tool for comprehensive understanding of stochastic membrane
processes.
PMID- 26437910
TI - The extended trajectory of hippocampal development: Implications for early memory
development and disorder.
AB - Hippocampus has an extended developmental trajectory, with refinements occurring
in the trisynaptic circuit until adolescence. While structural change should
suggest a protracted course in behavior, some studies find evidence of precocious
hippocampal development in the first postnatal year and continuity in memory
processes beyond. However, a number of memory functions, including binding and
relational inference, can be cortically supported. Evidence from the animal
literature suggests that tasks often associated with hippocampus (visual paired
comparison, binding of a visuomotor response) can be mediated by structures
external to hippocampus. Thus, a complete examination of memory development will
have to rule out cortex as a source of early memory competency. We propose that
early memory must show properties associated with full function of the
trisynaptic circuit to reflect "adult-like" memory function, mainly (1) rapid
encoding of contextual details of overlapping patterns, and (2) retention of
these details over sleep-dependent delays. A wealth of evidence suggests that
these functions are not apparent until 18-24 months, with behavioral
discontinuities reflecting shifts in the neural structures subserving memory
beginning approximately at this point in development. We discuss the implications
of these observations for theories of memory and for identifying and measuring
memory function in populations with typical and atypical hippocampal function.
PMID- 26437913
TI - Enhanced interannual precipitation variability increases plant functional
diversity that in turn ameliorates negative impact on productivity.
AB - Although precipitation interannual variability is projected to increase due to
climate change, effects of changes in precipitation variance have received
considerable less attention than effects of changes in the mean state of climate.
Interannual precipitation variability effects on functional diversity and its
consequences for ecosystem functioning are assessed here using a 6-year rainfall
manipulation experiment. Five precipitation treatments were switched annually
resulting in increased levels of precipitation variability while maintaining
average precipitation constant. Functional diversity showed a positive response
to increased variability due to increased evenness. Dominant grasses decreased
and rare plant functional types increased in abundance because grasses showed a
hump-shaped response to precipitation with a maximum around modal precipitation,
whereas rare species peaked at high precipitation values. Increased functional
diversity ameliorated negative effects of precipitation variability on primary
production. Rare species buffered the effect of precipitation variability on the
variability in total productivity because their variance decreases with
increasing precipitation variance.
PMID- 26437914
TI - Changes in Aortoiliac Anatomy After Elective Treatment of Infrarenal Abdominal
Aortic Aneurysms with a Sac Anchoring Endoprosthesis.
AB - OBJECTIVE: Endovascular aortic sealing (EVAS) with the Nellix endosystem
(Endologix, Irvine, CA, USA) is a new concept to treat infrarenal abdominal
aortic aneurysms (AAAs). By sealing the aneurysm, potential endoleaks may be
avoided. Early results of EVAS are good, but no data have been published
regarding peri-procedural changes in aortoiliac anatomy. In this study, 27
consecutive patients who underwent elective EVAS repair of an AAA were reviewed.
METHOD: Specific AAA (diameter, length from renal arteries to aortic bifurcation,
supra- and infrarenal neck angulation, AAA volume, thrombus volume, and flow
lumen volume), and iliac artery characteristics (length, angulation, location of
most severe angulation with reference to the origin of the common iliac artery)
were determined from pre- and post-procedural reconstructed computed tomography
angiograms. RESULTS: No type I or II endoleaks were seen at 30 day follow up.
Total AAA volume, suprarenal and infrarenal angulation, as well as aortic neck
diameter did not change significantly post-EVAS. AAA flow lumen increased
significantly (mean difference -4.4 mL, 95% CI 2.0 to -8.6 mL) and AAA thrombus
volume decreased (mean difference 3.2 mL, 95% CI 2.0 to -1.1 mL). AAA length
(125.7 mm vs. 123.1 mm), left common iliac artery length (57.6 mm vs. 55.3 mm),
and right and left maximum iliac artery angulation (right 37.4 degrees vs. 32.2
degrees ; left: 43.9 degrees vs. 38.4 degrees ) were reduced significantly and
the location of maximum angulation was further from the iliac artery origin post
EVAS, suggesting slight straightening of the aortoiliac anatomy. CONCLUSION: Most
aortoiliac anatomic characteristics remained unchanged post-EVAS. Filling of the
endobags to a pressure of 180 mmHg may lead to lost thrombus volume in some
patients, probably because liquid is squeezed into lumbar or the inferior
mesenteric artery. The absolute differences in pre- and post-EVAS aortoiliac
lengths were small, so pre-operative sizing is accurate for determining stent
length.
PMID- 26437915
TI - A novel dual EGFR/HER2 inhibitor KU004 induces cell cycle arrest and apoptosis in
HER2-overexpressing cancer cells.
AB - Human epidermal growth factor receptor 2 (HER2) is a validated therapeutic target
in cancer therapy, and HER2 protein-tyrosine kinase inhibitors have attracted
considerable attention in the field of searching for novel anticancer drug
candidates. In this study, we investigated the anticancer effect of KU004, a
novel dual EGFR and HER2 inhibitor in vitro and in vivo. In vitro, KU004
preferentially inhibited the growth of HER2-overexpressing breast and gastric
cell lines and HER2 expression level significantly correlated with response to
KU004. It blocked activation of EGFR, HER2 and downstream Akt and Erk and induced
G0/G1 arrest which was associated with downregulation of p53, p21, cyclin D1 and
CDK4 along with increase of p27 and dephosphorylation of pRb. Apoptosis occurred
in a caspase-dependent manner mainly via the extrinsic apoptotic pathway after
KU004 treatment. The in vitro efficacy of KU004 was comparable to that of
lapatinib. Moreover, KU004 suppressed the growth of NCI-N87 tumor and induced
apoptosis without causing apparent weight loss or obvious toxicity. Tumor volume
was significantly smaller in KU004-treated group than that in lapatinib-treated
group at comparable dose levels. Taken together, these findings demonstrate KU004
can be expected to be a promising anti-HER2 candidate.
PMID- 26437916
TI - Apoptotic and autophagic cell death induced by glucolaxogenin in cervical cancer
cells.
AB - The antiproliferative and cytotoxic activity of glucolaxogenin and its ability to
induce apoptosis and autophagy in cervical cancer cells are reported. We
ascertained that glucolaxogenin exerts an inhibitory effect on the proliferation
of HeLa, CaSki and ViBo cells in a dose-dependent manner. Analysis of DNA
distribution in the cell-cycle phase of tumor cells treated with glucolaxogenin
suggests that the anti-proliferative activity of this steroid is not always
dependent on the cell cycle. Cytotoxic activity was evaluated by detection of the
lactate dehydrogenase enzyme in supernatants from tumor cell cultures treated
with the steroid. Glucolaxogenin exhibited null cytotoxic activity. With respect
to the apoptotic activity, the generation of apoptotic bodies, the presence of
active caspase-3 and annexin-V, as well as the DNA fragmentation observed in all
tumor lines after treatment with glucolaxogenin suggests that this compound does
indeed induce cell death by apoptosis. Also, a significantly increased presence
of the LC3-II, LC3 and Lamp-1 proteins was evidenced with the ultrastructural
existence of autophagic vacuoles in cells treated with this steroidal glycoside,
indicating that glucolaxogenin also induces autophagic cell death. It is
important to note that this compound showed no cytotoxic effect and did not
affect the proliferative capacity of mononuclear cells obtained from normal human
peripheral blood activated by phytohaemagglutinin. Thus, glucolaxogenin is a
compound with anti-proliferative properties that induces programmed cell death in
cancer cell lines, though it is selective with respect to normal lymphocytic
cells. These findings indicate that this glycoside could have a selective action
on tumor cells and, therefore, be worthy of consideration as a therapeutic
candidate with anti-tumor potential.
PMID- 26437918
TI - Prediction of Drug Clearance in Premature and Mature Neonates, Infants, and
Children <=2 Years of Age: A Comparison of the Predictive Performance of 4
Allometric Models.
AB - The objective of this study was to evaluate the predictive performance of 4
allometric models to predict clearance in pediatric ages ranging from premature
neonates to children <=2 years of age. Four allometric models were used to
predict clearances of 28 drugs in children from preterm neonates to 2 years of
age (n = 564). The 4 models are (1) basal metabolic rate-dependent model; (2) age
dependent exponent model; (3) an allometric model based on kidney and liver
weights as well as kidney and liver blood flow; and (4) an allometric model based
on a fixed exponent of 0.75. The predictive performance of these models was
evaluated by comparing the predicted clearance of the studied drugs with the
observed clearance in an individual child. The results of the study indicated
that the 3 new proposed models predicted the mean clearance of the drugs with
reasonable accuracy (<=50% prediction error). On the other hand, the exponent of
0.75 produced substantial prediction error. Predicted individual clearance values
were >=50% in approximately 30% of the children by the proposed 3 methods and 73%
by exponent 0.75. The 3 new proposed allometric models can predict mean
clearances of drugs in children from premature neonates to <=2 years of age with
reasonable accuracy and are of practical value during pediatric drug development.
PMID- 26437919
TI - Genome-wide identification of long noncoding RNA genes and their potential
association with fecundity and virulence in rice brown planthopper, Nilaparvata
lugens.
AB - BACKGROUND: The functional repertoire of long noncoding RNA (lncRNA) has been
characterized in several model organisms, demonstrating that lncRNA plays
important roles in fundamental biological processes. However, they remain largely
unidentified in most species. Understanding the characteristics and functions of
lncRNA in insects would be useful for insect resources utilization and
sustainable pest control. METHODS: A computational pipeline was developed to
identify lncRNA genes in the rice brown planthopper, Nilaparvata lugens, a
destructive rice pest causing huge yield losses. Strand specific RT-PCR were used
to determine the transcription orientation of lncRNAs. RESULTS: In total, 2,439
lncRNA transcripts corresponding to 1,882 loci were detected from 12 whole
transcriptomes (RNA-seq) datasets, including samples from high fecundity (HFP),
low fecundity (LFP), I87i and C89i populations, in addition Mudgo and TN1
virulence strains. The identified N. lugens lncRNAs had low sequence similarities
with other known lncRNAs. However, their structural features were similar with
mammalian counterparts. N. lugens lncRNAs had shorter transcripts than protein
coding genes due to the lower exon number though their exons and introns were
longer. Only 19.9% of N. lugens lncRNAs had multiple alternatively spliced
isoforms. We observed biases in the genome location of N. lugens lncRNAs. More
than 30% of the lncRNAs overlapped with known protein-coding genes. These lncRNAs
tend to be co-expressed with their neighboring genes (Pearson correlation, p <
0.01, T-test) and might interact with adjacent protein-coding genes. In total, 19
148 lncRNAs were specifically-expressed in the samples of HFP, LFP, Mudgo, TN1,
I87i and C89i populations. Three lncRNAs specifically expressed in HFP and LFP
populations overlapped with reproductive-associated genes. DISCUSSION: The
structural features of N. lugens lncRNAs are similar to mammalian counterparts.
Coexpression and function analysis suggeste that N. lugens lncRNAs might have
important functions in high fecundity and virulence adaptability. CONCLUSIONS:
This study provided the first catalog of lncRNA genes in rice brown planthopper.
Gene expression and genome location analysis indicated that lncRNAs might play
important roles in high fecundity and virulence adaptation in N. lugens.
PMID- 26437920
TI - Luteimonas soli sp. nov., isolated from farmland soil.
AB - A yellow-pigmented bacterial strain, designated Y2T, was isolated from farmland
soil in Bengbu, Anhui province, China. Cells of strain Y2T were Gram-stain
negative, strictly aerobic, non-motile and rod-shaped. Strain Y2T grew optimally
at pH 7.0, 30 degrees C and in the presence of 2 % (w/v) NaCl. The DNA G+C
content was 68.9 mol%. The major fatty acids (>5 %) were iso-C15 : 0, iso-C17 :
0, summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1omega9c), iso-C11 : 0 3
OH and iso-C11 : 0. The major respiratory quinone was ubiquinone-8 (Q-8), and the
major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and
diphosphatidylglycerol. Phylogenetic analysis of the 16S rRNA gene sequences
showed that strain Y2T was most closely related to Luteimonas mephitis
B1953/27.1T (99.1 % 16S rRNA gene sequence similarity), followed by Luteimonas
lutimaris G3T (98.6 %), Luteimonas abyssi XH031T (96.2 %) and Luteimonas aquatica
RIB1-20T (96.0 %). Strain Y2T exhibited low DNA-DNA relatedness with Luteimonas
mephitis B1953/27.1T (43.6 +/- 0.5 %) and Luteimonas lutimaris G3T (43.9 +/- 2.1
%). On the basis of phenotypic, genotypic and phylogenetic evidence, strain Y2T
represents a novel species of the genus Luteimonas, for which the name Luteimonas
soli sp. nov. is proposed. The type strain is Y2T ( = ACCC 19799T = KCTC 42441T).
PMID- 26437922
TI - Impact of parental weight status on a school-based weight management programme
designed for Mexican-American children.
AB - BACKGROUND: While overweight and obese children are more likely to have
overweight or obese parents, less is known about the effect of parental weight
status on children's success in weight management programmes. OBJECTIVES: This
study was a secondary data analysis of a randomized controlled trial and
investigated the impact of having zero, one or two obese parents on children's
success in a school-based weight management programme. METHODS: Sixty-one Mexican
American children participated in a 24-week school-based weight management
intervention which took place in 2005-2006. Children's heights and weights were
measured at baseline, 3, 6 and 12 months. Parental weight status was assessed at
baseline. Repeated measures anova and ancova were conducted to compare changes in
children's weight within and between groups, respectively. RESULTS: Within-group
comparisons revealed that the intervention led to significant decreases in
standardized body mass index (zBMI) for children with zero (F = 23.16, P < .001)
or one obese (F = 4.99, P < .05) parent. Between-group comparisons indicated that
children with zero and one obese parents demonstrated greater decreases in zBMI
compared to children with two obese parents at every time point. CONCLUSIONS: The
school-based weight management programme appears to be most efficacious for
children with one or no obese parents compared to children with two obese
parents. These results demonstrate the need to consider parental weight status
when engaging in childhood weight management efforts.
PMID- 26437921
TI - Contribution of BDNF and DRD2 genetic polymorphisms to continued opioid use in
patients receiving methadone treatment for opioid use disorder: an observational
study.
AB - BACKGROUND: The heritability of opioid use disorder has been widely investigated;
however, the influence of specific genes on methadone treatment outcomes is not
well understood. The association between response to methadone treatment and
genes that are involved in substance use behaviors and reward mechanisms is
poorly understood, despite evidence suggesting their contribution to opioid use
disorder. The aim of this study was to investigate the effect of brain-derived
neurotrophic factor (BDNF) and dopamine receptor D2 (DRD2) polymorphisms on
continued opioid use among patients on methadone treatment for opioid use
disorder. METHODS: BDNF 196G>A (rs6265) and DRD2-241A>G (rs1799978) genetic
variants were examined in patients with opioid use disorder who were recruited
from methadone treatment clinics across Southern Ontario, Canada. We collected
demographic information, substance use history, blood for genetic analysis, and
urine to measure opioid use. We used regression analysis to examine the
association between continued opioid use and genetic variants, adjusting for age,
sex, ethnicity, methadone dose, duration in treatment, and number of urine
screens. RESULTS: Among 240 patients treated with methadone for opioid use
disorder, 36.3 percent (n = 87) and 11.3 percent (n = 27) had at least one risk
allele for rs6265 and rs1799978, respectively. These genetic variants were not
significantly associated with continued opioid use while on methadone maintenance
treatment [rs6265: odds ratio (OR) = 1.37, 95 % confidence interval (CI) = 0.792,
2.371, p = 0.264; rs1799978: OR 1.27, 95 % CI 0.511, 3.182, p = 0.603].
CONCLUSIONS: Despite an association of BDNF rs6265 and DRD2 rs1799978 with
addictive behaviors, these variants were not associated with continued illicit
opioid use in patients treated with methadone. Problematic use of opioids
throughout treatment with methadone may be attributed to nongenetic factors or a
polygenic effect requiring further exploration. Additional research should focus
on investigating these findings in larger samples and different populations.
PMID- 26437923
TI - Biodistribution and toxicity of spherical aluminum oxide nanoparticles.
AB - With the rapid development of the nano-industry, concerns about their potential
adverse health effects have been raised. Thus, ranking accurately their toxicity
and prioritizing for in vivo testing through in vitro toxicity test is needed. In
this study, we used three types of synthesized aluminum oxide nanoparticles
(AlONPs): gamma-aluminum oxide hydroxide nanoparticles (gamma-AlOHNPs), gamma-
and alpha-AlONPs. All three AlONPs were spherical, and the surface area was the
greatest for gamma-AlONPs, followed by the alpha-AlONPs and gamma-AlOHNPs. In
mice, gamma-AlOHNPs accumulated the most 24 h after a single oral dose.
Additionally, the decreased number of white blood cells (WBC), the increased
ratio of neutrophils and the enhanced secretion of interleukin (IL)-8 were
observed in the blood of mice dosed with gamma-AlOHNPs (10 mg kg(-1)). We also
compared their toxicity using four different in vitro test methods using six cell
lines, which were derived from their potential target organs, BEAS-2B (lung),
Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK-293 (kidney). The
results showed gamma-AlOHNPs induced the greatest toxicity. Moreover, separation
of particles was observed in a transmission electron microscope (TEM) image of
cells treated with gamma-AlOHNPs, but not gamma-AlONPs or alpha-AlONPs. In
conclusion, our results suggest that the accumulation and toxicity of AlONPs are
stronger in gamma-AlOHNPs compared with gamma-AlONPs and alpha-AlONPs owing their
low stability within biological system, and the presence of hydroxyl group may be
an important factor in determining the distribution and toxicity of spherical
AlONPs.
PMID- 26437924
TI - Vitamin D deficiency and its characteristics among patients with acute stroke at
a national referral hospital in Kampala Uganda.
AB - BACKGROUND: Vitamin D deficiency has been associated with acute stroke and other
cardiovascular diseases in the developed world. Low 25-hydroxyvitamin D (25OHD)
has been described in some populations in Sub-Saharan Africa (SSA) in spite of
adequate sunshine all year round. There is no information on the magnitude of
vitamin D deficiency among patients with stroke and other cardiovascular diseases
in Uganda or SSA. The aim of this study was to determine the burden and
characteristics of vitamin D deficiency among patients with acute stroke, the
most common form of cardiovascular events in SSA. METHODS: We conducted a cross
sectional study between October 2012 and March 2013. We consecutively recruited
142 subjects with acute stroke admitted to the medical wards of Mulago hospital.
We administered a pre-tested questionnaire to the study participants, and did a
detailed physical examination and laboratory evaluation. Serum levels of 25OHD
were determined using an electrochemiluminescence assay. Data were analyzed using
STATA version 12 software. RESULTS: The prevalence of vitamin D deficiency (25OHD
< 20 ng/ml) was 15 %. Longer hours of sunshine exposure decreased the likelihood
vitamin D deficiency significantly (adjusted OR 0.85, p = 0.03). Higher HDL
cholesterol had a significant inverse association with vitamin D deficiency
(adjusted OR 0.15, p = 0.02). In addition, the likelihood of vitamin D deficiency
increased with rising age (adjusted OR 1.03, p = 0.05). CONCLUSIONS: There was a
relatively low burden of vitamin D deficiency among patients with acute stroke in
Uganda. With increasing longevity and indoor lifestyles vitamin D deficiency may
assume a greater role in stroke and other cardiovascular diseases in tropical sub
Saharan Africa. Future studies on the mechanisms of vitamin D deficiency and its
relationship to outcomes among patients with stroke may be necessary.
PMID- 26437925
TI - Resolving Anomalies in Predicting Electrokinetic Energy Conversion Efficiencies
of Nanofluidic Devices.
AB - We devise a new approach for capturing complex interfacial interactions over
reduced length scales, towards predicting electrokinetic energy conversion
efficiencies of nanofluidic devices. By embedding several aspects of
intermolecular interactions in continuum based formalism, we show that our simple
theory becomes capable of representing complex interconnections between electro
mechanics and hydrodynamics over reduced length scales. The predictions from our
model are supported by reported experimental data, and are in excellent
quantitative agreement with molecular dynamics simulations. The present model,
thus, may be employed to rationalize the discrepancies between low energy
conversion efficiencies of nanofluidic channels that have been realized from
experiments, and the impractically high energy conversion efficiencies that have
been routinely predicted by the existing theories.
PMID- 26437926
TI - In Situ Transmission Electron Microscopy Observation of the Lithiation
Delithiation Conversion Behavior of CuO/Graphene Anode.
AB - The electrochemical conversion behavior of metal oxides as well as its influence
on the lithium-storage performance remains unclear. In this paper, we studied the
dynamic electrochemical conversion process of CuO/graphene as anode by in situ
transmission electron microscopy. The microscopic conversion behavior of the
electrode was further correlated with its macroscopic lithium-storage properties.
During the first lithiation, the porous CuO nanoparticles transformed to numerous
Cu nanograins (2-3 nm) embedded in Li2O matrix. The porous spaces were found to
be favorable for accommodating the volume expansion during lithium insertion. Two
types of irreversible processes were revealed during the lithiation-delithiation
cycles. First, the nature of the charge-discharge process of CuO anode is a
reversible phase conversion between Cu2O and Cu nanograins. The delithiation
reaction cannot recover the electrode to its pristine structure (CuO), which is
responsible for about ~55% of the capacity fading in the first cycle. Second,
there is a severe nanograin aggregation during the initial conversion cycles,
which leads to low Coulombic efficiency. This finding could also account for the
electrochemical behaviors of other transition metal oxide anodes that operate
with similar electrochemical conversion mechanism.
PMID- 26437927
TI - Selection of reference genes for analysis of stress-responsive genes after
challenge with viruses and temperature changes in the silkworm Bombyx mori.
AB - Viruses and high temperature (HT) are the primary threats to silkworms. Changes
in the expression of stress-response genes can be measured using quantitative
polymerase chain reaction (qPCR) after exposure to viruses or HT. However,
appropriate reference genes (RGs) for qPCR data normalization have not been
established in this organism. In this study, we summarized the RGs used in the
previous silkworm studies after infection with Bombyx mori nucleopolyhedrovirus
(BmNPV), B. mori cytoplasmic polyhedrosis virus (BmCPV), or B. mori densovirus
(BmDNV) or after HT treatment. The expression levels of these RGs were extracted
from silkworm transcriptome data to screen for candidate RGs that were unaffected
by the experimental conditions. Actin-1 (A1), actin-3 (A3), glyceraldehyde-3
phosphate dehydrogenase (GAPDH), and translation initiation factor 4a (TIF-4A)
were selected for further qPCR verification. The results of RNA-seq and qPCR
showed that GAPDH and TIF-4A were suitable RGs after BmNPV challenge or HT
stress, whereas TIF-4A was an appropriate RG for BmCPV or BmDNV-Z challenge in
silkworms. These results suggested that TIF-4A may be the most appropriate RG for
gene expression analysis after challenge with viruses or HT in silkworms.
PMID- 26437928
TI - Erratum to: Identification and characterization of microRNAs at different
flowering developmental stages in moso bamboo (Phyllostachys edulis) by high
throughput sequencing.
PMID- 26437929
TI - Muscle Ultrasound in Patients with Glycogen Storage Disease Types I and III.
AB - In glycogen storage diseases (GSDs), improved longevity has resulted in the need
for neuromuscular surveillance. In 12 children and 14 adults with the "hepatic"
(GSD-I) and "myopathic" (GSD-III) phenotypes, we cross-sectionally assessed
muscle ultrasound density (MUD) and muscle force. Children with both "hepatic"
and "myopathic" GSD phenotypes had elevated MUD values (MUD Z-scores: GSD-I > 2.5
SD vs. GSD-III > 1 SD, p < 0.05) and muscle weakness (GSD-I muscle force; p <
0.05) of myopathic distribution. In "hepatic" GSD-I adults, MUD stabilized (GSD-I
adults vs. GSD-I children, not significant), concurring with moderate muscle
weakness (GSD-I adults vs. healthy matched pairs, p < 0.05). In "myopathic" GSD
III adults, MUD increased with age (MUD-GSD III vs. age: r = 0.71-0.83, GSD-III
adults > GSD-III children, p < 0.05), concurring with pronounced muscle weakness
(GSD-III adults vs. GSD-I adults, p < 0.05) of myopathic distribution. Children
with "hepatic" and "myopathic" GSD phenotypes were both found to have myopathy.
Myopathy stabilizes in "hepatic" GSD-I adults, whereas it progresses in
"myopathic" GSD-III adults. Muscle ultrasonography provides an excellent, non
invasive tool for neuromuscular surveillance per GSD phenotype.
PMID- 26437931
TI - Physico-chemical and bacteriological quality of drinking water of different
sources, Jimma zone, Southwest Ethiopia.
AB - BACKGROUND: The quality of drinking water has always been a major health concern,
especially in developing countries, where 80% of the disease cases are attributed
to inadequate sanitation and use of polluted water. The inaccessibility of
potable water to large segment of a population in the rural communities is the
major health concern in most part of developing countries. This study was
designed to evaluate the physico-chemical and bacteriological qualities of
drinking water of different sources in the study area. METHODS: The study was
conducted at Serbo town and selected kebeles around the same town in Kersa
district of Jimma Zone, southwest Ethiopia. Socio-demographic characteristics of
the study populations were gathered using structured and pre-tested
questionnaires. Standard microbiological methods were employed for determination
of bacterial load and detection of coliforms. Physico-chemical analyses
[including total dissolved substances (TDS), total suspended substances (TSS),
biological oxygen demand (BOD), nitrate and phosphate concentrations, turbidity
and electrical conductivities] were conducted following guidelines of American
Public Health Association and WHO. Correlations among measured parameters of
water samples collected from different water sources were computed using SPSS
software (version 20). RESULT: Only 18.1% (43/237) of the study population had
access to tap water in the study area. More than 50% of the community relies on
open field waste disposal. Members of the family Enterobacteriaceae, Bacillus and
Pseudomonas were among dominant bacterial isolates in the water samples. All
water samples collected from unprotected water sources were positive for total
coliforms and fecal coliforms (FC). Accordingly, FC were detected in 80% of the
total samples with counts ranging between 0.67 and 266.67 CFU/100 ml although
66.67% of tap water samples were negative for FC. The recorded temperature and pH
ranged between 20.1-29.90 degrees C and 5.64-8.14, respectively. The lowest and
highest mean TDS were 116 and 623 mg/l, respectively. Furthermore, the mean
concentration of TSS ranged between 2.07 and 403.33 mg/l. Turbidity, electric
conductivity, and nitrate concentration of the water samples ranged,
respectively, between 0.01-65.4 NTU, 30.6-729 MUS/cm, and below detection limit
to 95.80 mg/l. In addition, the mean dissolved oxygen values were found to be
between 1.62 and 10.71 mg/l; whereas BOD was within the range of 8-77 mg/l. In
all water samples, the concentrations of zinc were within the WHO maximum
permissible limits (3 mg/l) although the lead concentration in about 66.7% of the
samples exceeded the maximum permissible limit (0.01 mg/l). CONCLUSION: The
present study has revealed that some of the bacteriological data and physico
chemical parameters of the different water sources had values beyond the maximum
tolerable limits recommended by WHO. Thus, it calls for appropriate intervention,
including awareness development work and improving the existing infrastructure in
order to minimize the potential health problems of those communities currently
realizing of the available water sources.
PMID- 26437930
TI - Effect of oral administration of low-dose follicle stimulating hormone on
hyperandrogenized mice as a model of polycystic ovary syndrome.
AB - BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a widespread reproductive
disorder characterized by a disruption of follicular growth and anovulatory
infertility. In women with PCOS, follicular growth and ovulation can be induced
by subcutaneous injections of low doses of follicle stimulating hormone (FSH).
The aim of this study was to determine the effect of oral administration of
recombinant human FSH (rhFSH) on follicle development in a PCOS murine model.
Moreover, since it is unlikely that intact rhFSH is present into the circulation
after oral administration, the biological activity of a peptide fragment, derived
from the predicted enzymatic cleavage sites with the FSH molecule, was
investigated in vitro on cumulus-enclosed oocytes (COCs). METHODS: Female
peripubertal mice were injected with dehydroepiandrosterone (DHEA) diluted in
sesame oil for 20 consecutive days and orally treated with a saline solution of
rhFSH. A control group received only sesame oil and saline solution. At the end
of treatments, blood was analyzed for hormone concentrations and ovaries were
processed for morphological analysis. The presumptive bioactive peptide was added
during in vitro maturation of bovine COCs and the effects on cumulus expansion
and on maturation rate were evaluated. RESULTS: DHEA treatment increased serum
levels of testosterone, estradiol and progesterone as well as the percentage of
cystic follicles. Orally administered rhFSH restored estradiol level and reduced
the percentage of cystic follicles. Despite these results indicating a reduction
of the severity of PCOS in the mouse model, the presumptive bioactive peptide did
not mimic the effect of rhFSH and failed to induce bovine cumulus expansion and
oocyte maturation in vitro. CONCLUSIONS: Although further studies are needed, the
present data supports the concept that orally administrated FSH could attenuate
some of the characteristic of PCOS in the mouse model.
PMID- 26437932
TI - A novel homozygous MPV17 mutation in two families with axonal sensorimotor
polyneuropathy.
AB - BACKGROUND: Mutations in MPV17 cause the autosomal recessive disorder
mitochondrial DNA depletion syndrome 6 (MTDPS6), also called Navajo
neurohepatopathy (NNH). Clinical features of MTDPS6 is infantile onset of
progressive liver failure with seldom development of progressive neurologic
involvement. METHODS: Whole exome sequencing (WES) was performed to isolate the
causative gene of two unrelated neuropathy patients (9 and 13 years of age) with
onset of the syndrome. Clinical assessments and biochemical analysis were
performed. RESULTS: A novel homozygous mutation (p.R41Q) in MPV17 was found by
WES in both patients. Both showed axonal sensorimotor polyneuropathy without
liver and brain involvement, which is neurophysiologically similar to axonal
Charcot-Marie-Tooth disease (CMT). A distal sural nerve biopsy showed an almost
complete loss of the large and medium-sized myelinated fibers compatible with
axonal neuropathy. An in vitro assay using mouse motor neuronal cells
demonstrated that the abrogation of MPV17 significantly affected cell integrity.
In addition, the expression of the mutant protein affected cell proliferation.
These results imply that both the loss of normal function of MPV17 and the gain
of detrimental effects of the mutant protein might affect neuronal function.
CONCLUSION: We report a novel homozygous mutation in MPV17 from two unrelated
patients harboring axonal sensorimotor polyneuropathy without
hepatoencephalopathy. This report expands the clinical spectrum of diseases
caused by mutations of MPV17, and we recommend MPV17 gene screening for axonal
peripheral neuropathies.
PMID- 26437933
TI - An accurate and efficient experimental approach for characterization of the
complex oral microbiota.
AB - BACKGROUND: Currently, taxonomic interrogation of microbiota is based on
amplification of 16S rRNA gene sequences in clinical and scientific settings.
Accurate evaluation of the microbiota depends heavily on the primers used, and
genus/species resolution bias can arise with amplification of non-representative
genomic regions. The latest Illumina MiSeq sequencing chemistry has extended the
read length to 300 bp, enabling deep profiling of large number of samples in a
single paired-end reaction at a fraction of the cost. An increasingly large
number of researchers have adopted this technology for various microbiome studies
targeting the 16S rRNA V3-V4 hypervariable region. RESULTS: To expand the
applicability of this powerful platform for further descriptive and functional
microbiome studies, we standardized and tested an efficient, reliable, and
straightforward workflow for the amplification, library construction, and
sequencing of the 16S V1-V3 hypervariable region using the new 2 * 300 MiSeq
platform. Our analysis involved 11 subgingival plaque samples from diabetic and
non-diabetic human subjects suffering from periodontitis. The efficiency and
reliability of our experimental protocol was compared to 16S V3-V4 sequencing
data from the same samples. Comparisons were based on measures of observed
taxonomic richness and species evenness, along with Procrustes analyses using
beta(beta)-diversity distance metrics. As an experimental control, we also
analyzed a total of eight technical replicates for the V1-V3 and V3-V4 regions
from a synthetic community with known bacterial species operon counts. We show
that our experimental protocol accurately measures true bacterial community
composition. Procrustes analyses based on unweighted UniFrac beta-diversity
metrics depicted significant correlation between oral bacterial composition for
the V1-V3 and V3-V4 regions. However, measures of phylotype richness were higher
for the V1-V3 region, suggesting that V1-V3 offers a deeper assessment of
population diversity and community ecology for the complex oral microbiota.
CONCLUSION: This study provides researchers with valuable experimental evidence
for the selection of appropriate 16S amplicons for future human oral microbiome
studies. We expect that the tested 16S V1-V3 framework will be widely applicable
to other types of microbiota, allowing robust, time-efficient, and inexpensive
examination of thousands of samples for population, phylogenetic, and functional
crossectional and longitutidal studies.
PMID- 26437934
TI - Cranioplasty complications and risk factors associated with bone flap resorption.
AB - BACKGROUND: Decompressive craniectomy (DC) may be performed in patients with
acutely raised intracranial pressure due to traumatic brain injury or stroke. It
is later followed by a cranioplasty procedure (CP) in the surviving patients.
This procedure is associated with a high frequency of post-operative
complications. Identifying risk factors for these adverse events is important in
order to improve the clinical outcome. This study examines possible predictive
parameters for post-operative complications in CP. METHODS: Retrospective, single
institution review of all patients undergoing a DC for acutely raised
intracranial pressure over a 10 year period at Oslo University Hospital Ulleval,
Norway. Subsequent CP using autologous bone flaps or synthetic implants were
registered along with all post-operative complications. Predictors of post
operative complications were identified using uni -and multivariable regression
analyses. RESULTS: A DC was carried out in 125 patients, of whom 33 died, 4 were
lost to follow-up, and 1 (an infant) later underwent cranial remodeling. A CP was
performed in the remaining 87 patients. Post-operative complications were
recorded in 31 (36 %) patients of whom 22 lost their primary implant. Surgical
site infection (SSI) and bone flap resorption (BFR) were the two most common
complications, affecting 8 (9.2 %) and 14 (19.7 %) patients, respectively. Only
BFR was associated with some of the recorded variables. Using multivariable
logistic regression analysis, young age (OR = 0.94, 95 % CI 0.88-1.00, p = 0.04),
bone flap fragmentation (OR = 14.3, 95 % CI 2.26-89, p = 0.005), long storage
time (OR = 1.03, 95 % CI 1.00-1.04, p = 0.02) and Glasgow Outcome Scale at the
time of cranioplasty (OR = 2.55, 95 % CI 1.04-6.23, p = 0.04) were found to be
significant risk factors for bone flap resorption. CONCLUSIONS: Cranioplasty
after decompressive craniectomy carries a high rate of complications. In this
study, SSI and BFR were the two most common complications of which predictive
clinical parameters could be identified for BFR only. The results indicate that
synthetic implants may be considered in pediatric patients and in cases with
fragmented bone flaps or delayed time to cranioplasty. Although the rate of
complications was high, 73 % had a successful reinsertion of the autologous graft
at a low cost. We feel this result justifies the continued use of cryopreserved
bone flaps.
PMID- 26437935
TI - Health status among black African-born women in Kansas City: a preliminary
assessment.
AB - BACKGROUND: Health information and statistics for Black foreign-born women in the
United States are under-reported or not available. Black foreign-born women
typically are classified under the general category of African American, ignoring
the heterogeneity that exists in the United States Black population. It is
important to identify health issues and behaviors of African-born women to
effectively address health disparities. METHODS: Black African-born women (N =
29), 20 years or older completed a survey about general and women's health,
health history, acculturation, lifestyle, social and health challenges, beliefs
about breast cancer. Data were analyzed using SPSS 14.0 software. Categorical
variables were summarized with frequencies and percentages and continuous
variables were summarized with means and standard variation. A Likert scale
(strongly agree, agree, disagree, and strongly disagree) was used to assess
beliefs about breast cancer. RESULTS: Most (71.4%) participants had a high school
education or more, 70% were employed, and 50% had health insurance. Two-thirds
received health care from primary care doctors, 20.7% from health departments,
and 39.3% got annual checkups. Lack of jobs, healthcare cost, language barrier,
discrimination, and child care were the top social issues faced by participants.
High blood pressure, obesity, oral health, HIV/AIDS, and diabetes were indicated
as the most common health problems. The percent of participants (60%) that had
not had a mammogram within the previous 2 years was more than the state average
(24%) for women 40 years and older reported by the Kansas Department of Health
and Environment. The percent of participants (40%) that had a mammogram within
the previous 2 years was lower than the national average (73.2%) for African
American women. CONCLUSIONS: Study provides a snapshot of social concerns and
health issues in an African population residing in Midwestern United States.
Understanding the socio-cultural characteristics of this population is necessary
to address health disparities.
PMID- 26437936
TI - Palliative surgical intervention in metastatic colorectal carcinoma: a
prospective analysis of quality of life.
AB - AIM: Quality of life (QOL) was assessed after palliative surgery for incurable
metastatic colorectal cancer (CRC). METHOD: Newly diagnosed patients with
incurable metastatic CRC who were offered elective palliative surgical
intervention were included. The European Organization for Research and Treatment
of Cancer QLQ-C30 and QLQ-CR29 questionnaire was used for the assessment of QOL
at baseline and at 3 and 6 months after surgery. Generalized estimating equations
were used to estimate the mean change in the QOL score from baseline. RESULTS:
Twenty-four patients formed the study group. Sixteen underwent resection of the
primary tumour and eight had a proximal diversion or bypass. The Global Health
(GH) score and Social Functioning (SF) score improved at 3 and 6 months after
intervention respectively (GH +11, P = 0.021; SF +15, P = 0.005). Mean anxiety
scores were markedly improved from the baseline of 51 to 71 (P = 0.004, 3 months)
and 76 (P = 0.002, 6 months). Weight concerns also improved significantly when
compared with baseline (3 months, +20, P < 0.001; 6 months, +14, P = 0.012).
Symptoms of diarrhoea (3 months, --17, P = 0.007; 6 months,--16, P = 0.008) and
nausea (--8, P = 0.032) improved. CONCLUSION: In patients with incurable
metastatic CRC, surgery improved QOL.
PMID- 26437937
TI - Advances in the anatomic study of the interscapular region of the cat.
AB - BACKGROUND: New clinical oriented approaches are supported by the integration of
advanced imaging techniques, e.g. computed tomography and magnetic resonance,
with gross anatomy imaging. The interscapular region of the cat is a typical site
of a highly invasive infiltrative pathology, i.e. Feline Injection-Site Sarcoma.
Even if chemotherapy and radiotherapy have been considered as pre-surgical
therapies, extensive surgery is still the recommended treatment. Evidence
suggested that the relationships between muscles, infiltrative mass and adjacent
musculoskeletal structures could change according to the forelimb positions: a
fact to be duly considered while planning the surgical approach. Anatomic and
tomographic atlases provide only images of the interscapular region from cats
positioned with their forelimbs extended cranially, which means that, they do not
record musculoskeletal modifications due to the forelimb movements. Aim of this
study was to provide detailed images of the changes occurring in the
musculoskeletal structures of the interscapular region of cats according to their
forelimb position by comparing cross-sectional gross anatomy, computed tomography
and magnetic resonance imaging. RESULTS: We provide an atlas of normal cross
sectional anatomy, computed tomography and magnetic resonance imaging of the
interscapular region of the cat, from the fifth cervical vertebra to the fifth
thoracic vertebra. We compare and couple the slices obtained both in flexed and
extended forelimb positioning with the animal maintained in sternal recumbency.
CONCLUSION: This study shows a new and dynamic way to investigate the
interscapular region of the cat and provides anatomical references for in vivo
computed tomography and magnetic resonance imaging, considering changes in the
muscular form according to the forelimb positioning. We believe that an in-depth
anatomical knowledge of the interscapular region may be helpful to approach the
study of any pathology located there and, in particular, to set up an appropriate
therapy for the feline injection-site sarcoma.
PMID- 26437938
TI - A case of Listeria monocytogenes endophthalmitis with recurrent inflammation and
novel management.
AB - BACKGROUND: Listeria monocytogenes is a rare cause of endogenous endophthalmitis.
In the limited number of reported Listeria endophthalmitis cases, visual acuity
outcomes have been very poor. FINDINGS: Here, we report a case of Listeria
endophthalmitis that was complicated by recurrent inflammation. The patient
required treatment with both intravitreal and long-term systemic antibiotics. An
anterior chamber washout was necessary for the patient to regain 20/20 visual
acuity. CONCLUSIONS: This case highlights the importance of considering Listeria
early in the disease course, as it has low sensitivity to standard empiric
antibiotic therapy. It also stresses the importance of addressing damaging
inflammation in infectious conditions.
PMID- 26437939
TI - Family planning to promote physical activity: a randomized controlled trial
protocol.
AB - BACKGROUND: Physical activity is associated with the reduction of several chronic
conditions in adults. Additionally, physical activity is extremely important for
children for their development and cognitive functioning and also to create a
physically active lifestyle that continues into adulthood. Despite the known
benefits of physical activity, only one in five adults are achieving the public
health recommendations of 150 minutes of moderate-to-vigorous physical activity
per week and only 13 % of boys and 6 % of girls between the ages of 5 and 17
years are meeting the guidelines of 60 minutes per day. This study aims to
evaluate whether a planning condition improves adherence to regular physical
activity compared to an education-only control condition among families. Families
are eligible if there is at least one child between the ages of 6 and 12 years
who is not meeting the Canadian Physical Activity Guidelines. METHODS/DESIGN: A
six-month longitudinal randomized controlled trial will be used to compare the
two conditions. Materials will be delivered at baseline with 'booster' sessions
at six weeks and three months. Participants will be assessed at baseline and at
six months with a fitness test, as well as questionnaires and accelerometery at
baseline, six weeks, three months and six months. A total of 137 families have
been recruited thus far from Greater Victoria. This study is ongoing and
recruitment will continue until December 2015 with the target goal of reaching
160 families. DISCUSSION: This protocol describes the implementation of a
randomized controlled trial that utilizes planning strategies to try and increase
physical activity among families. Research findings could be useful in public
health in providing effective strategies to families to help decrease sedentary
lifestyles. Additionally, findings may help to inform future interventions aimed
at increasing physical activity among families. TRIAL REGISTRATION: This trial
was registered on June 5, 2012 with the Clinical Trials Registry maintained by
the National Library of Medicine at the National Institutes of Health. The
registration ID is NCT01882192.
PMID- 26437942
TI - Behavior Genetics Association 45th Annual Meeting Abstracts.
PMID- 26437940
TI - Placental vascularization alterations in hypertensive disorders complicating
pregnancy (HDCP) and small for gestational age with HDCP using three-dimensional
power doppler in a prospective case control study.
AB - BACKGROUND: Hypertensive disorders complicating pregnancy (HDCP) continues to be
a leading cause of maternal and neonatal mortality and morbidity. The clinical
value of placental three-dimensional power Doppler (3DPD) in assessing HDCP
requires further confirmation. The research was developed to assess changes of
placental vascularity in HDCP using 3DPD and to investigate the placental
vascularity in small for gestational age (SGA) compared with not-SGA in patients
with HDCP. METHODS: There were 126 normotensive and 128 hypertensive pregnant
women included in this prospective case-control study from March 2011 to March
2013. Pregnant women underwent 3DPD. Vascularization index (VI), flow index (FI)
and vascularization flow index (VFI) were obtained. The placental 3DPD indices,
umbilical artery systolic and diastolic ratio (S/D) and pregnancy outcomes were
compared between the groups. RESULTS: The placental VI and VFI were significantly
lower in hypertensive women compared with normotensive women (P < 0.001 and P =
0.014, respectively), and these parameters were significantly reduced in severe
preeclampsia (P < 0.001 and P = 0.003, respectively). A weak correlation was
found between VI and umbilical artery S/D in HDCP group (r = -0.277, P = 0.001).
In HDCP population, neonates who were postnatally diagnosed with SGA had lower VI
(P = 0.041) and higher S/D (P < 0.001). DISCUSSION: The placental vascularity
indices decreased in hypertensive women and the reduction inplacental perfusion
was consistent with the severity of the hypertensive disorder. The associations
betweenplacental vascularization and umbilical artery impedance may be valuable
for further researches and arerequired confirmation. The significant differences
in the 3DPD placental vascularization between SGA andnot-SGA in hypertensive
pregnancy population may show some clinical importance that we could use tobetter
assess or predict the progression and adverse outcomes in the future. Although
3DPD quantificationhas been widely used in multiple publications, we have to
acknowledge its limitations. CONCLUSIONS: The intraplacental vascularization was
poor in HDCP, and especially in severe preeclampsia. Neonates with SGA had poor
placental vascularization and higher umbilical artery S/D. Further studies should
focus on the clinical assessment of placental 3DPD as well as a combination of
placental 3DPD and other fetal Doppler indices to better predict the development
and outcomes of preeclampsia.
PMID- 26437943
TI - Phylogenetic approaches to microbial community classification.
AB - BACKGROUND: The microbiota from different body sites are dominated by different
major groups of microbes, but the variations within a body site such as the mouth
can be more subtle. Accurate predictive models can serve as useful tools for
distinguishing sub-sites and understanding key organisms and their roles and can
highlight deviations from expected distributions of microbes. Good classification
depends on choosing the right combination of classifier, feature representation,
and learning model. Machine-learning procedures have been used in the past for
supervised classification, but increased attention to feature representation and
selection may produce better models and predictions. RESULTS: We focused our
attention on the classification of nine oral sites and dental plaque in
particular, using data collected from the Human Microbiome Project. A key focus
of our representations was the use of phylogenetic information, both as the basis
for custom kernels and as a way to represent sets of microbes to the classifier.
We also used the PICRUSt software, which draws on phylogenetic relationships to
predict molecular functions and to generate additional features for the
classifier. Custom kernels based on the UniFrac measure of community
dissimilarity did not improve performance. However, feature representation was
vital to classification accuracy, with microbial clade and function
representations providing useful information to the classifier; combining the two
types of features did not yield increased prediction accuracy. Many of the best
performing clades and functions had clear associations with oral microflora.
CONCLUSIONS: The classification of oral microbiota remains a challenging problem;
our best accuracy on the plaque dataset was approximately 81 %. Perfect accuracy
may be unattainable due to the close proximity of the sites and intra-individual
variation. However, further exploration of the space of both classifiers and
feature representations is likely to increase the accuracy of predictive models.
PMID- 26437944
TI - The 14-3-3 Gene Function of Cryptococcus neoformans Is Required for its Growth
and Virulence.
AB - Cryptococcus neoformans is a life-threatening pathogenic yeast that causes
devastating meningoencephalitis. The mechanism of cryptococcal brain invasion is
largely unknown, and recent studies suggest that its extracellular microvesicles
may be involved in the invasion process. The 14-3-3 protein is abundant in the
extracellular microvesicles of C. neoformans, and the 14-3-3-GFP fusion has been
used as the microvesicle's marker. However, the physiological role of 14-3-3 has
not been explored. In this report, we have found that C. neoformans contains a
single 14-3-3 gene that apparently is an essential gene. To explore the functions
of 14-3-3, we substituted the promoter region of the 14-3-3 with the copper
controllable promoter CTR4. The CTR4 regulatory strain showed an enlarged cell
size, drastic changes in morphology, and a decrease in the thickness of the
capsule under copper-enriched conditions. Furthermore, the mutant cells produced
a lower amount of total proteins in their extracellular microvesicles and reduced
adhesion to human brain microvascular endothelial cells in vitro. Proteomic
analyses of the protein components under 14-3-3-overexpressed and -suppressed
conditions revealed that the 14-3-3 function(s) might be associated with the
microvesicle biogenesis. Our results support that 14-3-3 has diverse pertinent
roles in both physiology and pathogenesis in C. neoformans. Its gene functions
are closely relevant to the pathogenesis of this fungus.
PMID- 26437945
TI - Bacterial Community Structure Shifted by Geosmin in Granular Activated Carbon
System of Water Treatment Plants.
AB - We investigated the relation between the presence of geosmin in water and the
bacterial community structure within the granular activated carbon (GAC) system
of water treatment plants in South Korea. GAC samples were collected in May and
August of 2014 at three water treatment plants (Sungnam, Koyang, and Yeoncho in
Korea). Dissolved organic carbon and geosmin were analyzed before and after GAC
treatment. Geosmin was found in raw water from Sungnam and Koyang water treatment
plants but not in that from Yeoncho water treatment plant. Interestingly, but not
surprisingly, the 16S rRNA clone library indicated that the bacterial communities
from the Sungnam and Koyang GAC systems were closely related to geosmin-degrading
bacteria. Based on the phylogenetic tree and multidimensional scaling plot,
bacterial clones from GAC under the influence of geosmin were clustered with
Variovorax paradoxus strain DB 9b and Comamonas sp. DB mg. In other words, the
presence of geosmin in water might have inevitably contributed to the growth of
geosmin degraders within the respective GAC system.
PMID- 26437946
TI - A Color-Reaction-Based Biochip Detection Assay for RIF and INH Resistance of
Clinical Mycobacterial Specimens.
AB - The widespread occurrence of drug-resistant Mycobacterium tuberculosis places
importance on the detection of TB (tuberculosis) drug susceptibility.
Conventional drug susceptibility testing (DST) is a lengthy process. We developed
a rapid enzymatic color-reaction-based biochip assay. The process included
asymmetric multiplex PCR/templex PCR, biochip hybridization, and an enzymatic
color reaction, with specific software for data operating. Templex PCR (tem- PCR)
was applied to avoid interference between different primers in conventional
multiplex- PCR. We applied this assay to 276 clinical specimens (including 27
sputum, 4 alveolar lavage fluid, 2 pleural effusion, and 243 culture isolate
specimens; 40 of the 276 were non-tuberculosis mycobacteria specimens and 236
were M. tuberculosis specimens). The testing process took 4.5 h. A sensitivity of
50 copies per PCR was achieved, while the sensitivity was 500 copies per PCR when
tem-PCR was used. Allele sequences could be detected in mixed samples at a
proportion of 10%. Detection results showed a concordance rate of 97.46%
(230/236) in rifampicin resistance detection (sensitivity 95.40%, specificity
98.66%) and 96.19% (227/236) in isoniazid (sensitivity 93.59%, specificity
97.47%) detection with those of DST assay. Concordance rates of testing results
for sputum, alveolar lavage fluid, and pleural effusion specimens were 100%. The
assay provides a potential choice for TB diagnosis and treatment.
PMID- 26437947
TI - Enzyme-Catalyzed Henry Reaction in Choline Chloride-Based Deep Eutectic Solvents.
AB - The enzyme-catalyzed Henry reaction was realized using deep eutectic solvents
(DESs) as a reaction medium. The lipase from Aspergillus niger (lipase AS) showed
excellent catalytic activity toward the substrates aromatic aldehydes and
nitromethane in choline chloride:glycerol at a molar ratio of 1:2. Addition of 30
vol% water to DES further improved the lipase activity and inhibited DES
catalyzed transformation. A final yield of 92.2% for the lipase AS-catalyzed
Henry reaction was achieved under optimized reaction conditions in only 4 h. In
addition, the lipase AS activity was improved by approximately 3-fold in a DES
water mixture compared with that in pure water, which produced a final yield of
only 33.4%. Structural studies with fluorescence spectroscopy showed that the
established strong hydrogen bonds between DES and water may be the main driving
force that affects the spatial conformation of the enzyme, leading to a change in
lipase activity. The methodology was also extended to the aza-Henry reaction,
which easily occurred in contrast to that in pure water. The enantioselectivity
of both Henry and aza-Henry reactions was not found. However, the results are
still remarkable, as we report the first use of DES as a reaction medium in a
lipase-catalyzed Henry reaction.
PMID- 26437948
TI - Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells.
AB - Numerous plants have been documented to contain phenolic compounds. Thymol is one
among these phenolic compounds that possess a repertoire of pharmacological
activities, including anti-inflammatory, anticancer, antioxidant, antibacterial,
and antimicrobial effects. Despite of the plethora of affects elicited by thymol,
its activity profile on gastric cancer cells is not explored. In this study, we
discovered that thymol exerts anticancer effects by suppressing cell growth,
inducing apoptosis, producing intracellular reactive oxygen species, depolarizing
mitochondrial membrane potential, and activating the proapoptotic mitochondrial
proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in
human gastric AGS cells. The outcomes of this study displayed that thymol, via an
intrinsic mitochondrial pathway, was responsible for inducing apoptosis in
gastric AGS cells. Hence, thymol might serve as a tentative agent in the future
to treat cancer.
PMID- 26437949
TI - Melanin Biosynthesis Inhibition Effects of Ginsenoside Rb2 Isolated from Panax
ginseng Berry.
AB - Ginsenoside Rb2 (Gin-Rb2) was purified from the fruit extract of Panax ginseng.
Its chemical structure was measured by spectroscopic analysis, including HR-FAB
MS, (1)H-NMR, and IR spectroscopy. Gin-Rb2 decreased potent melanogenesis in
melan-a cells, with 23.4% at 80 MUM without cytotoxicity. Gin-Rb2 also decreased
tyrosinase and MITF protein expression in melan-a cells. Furthermore, Gin-Rb2
presented inhibition of the body pigmentation in the zebrafish in vivo system and
reduced melanin contents and tyrosinase activity. These results show that Gin-Rb2
isolated from P. ginseng may be an effective skin-whitening agent via the in
vitro and in vivo systems.
PMID- 26437950
TI - Identifying Desistance Pathways in a Higher Education Program for Formerly
Incarcerated Individuals.
AB - The link between education and crime is a topic that requires special attention
with respect to the converging influence of individual, social, and environmental
factors. This article will investigate the educational pathways followed by
students in a higher education program for formerly incarcerated individuals at a
large state university in the northeastern United States. Specifically, it will
explore the extent to which their postincarceration educational experiences
served as a "hook for change" and also related impediments tied to street
influences, financial constraints, stigma, academic and social development. Data
were collected from a sample of 34 current and former students in the program,
each of whom participated in a face-to-face interview. The higher education
program played a key role in propelling the desistance process for research
participants. This article will discuss how personal agency can be sustained
through participation in higher education post release and the implications for
future research on crime avoidance.
PMID- 26437951
TI - Teachers of various school grades and representations of epilepsy: problems,
relational aspects and perspectives of life quality.
AB - INTRODUCTION: The analysis of the representations of the health of their students
by teachers is key to the understanding of the attitudes and behaviors that, in
general, take place inside the school community and the educational processes. In
fact, social attitudes by teachers and individual within the school environment
are often the result of simple categorization and stereotypes, which hinder the
process of evolutionary change. AIMS: On these premises it was necessary to
investigate the level of knowledge of the epilepsy syndrome, the representations
by a group of teachers of the quality of life of people with epilepsy and the
representations of the interpersonal relationships between students with epilepsy
and their classmates. METHODOLOGY: We used an ad hoc questionnaire, with 33
multiple choice answers, focusing on these variables: work seniority, experience
with epileptic students, special education or main teacher. PARTICIPANTS: The
sample consisted of 113 female teachers with a mean age of 44.4. RESULTS: There
aren't significant differences between the answers of special education and main
teachers: a) teachers with work seniority > 11 years showed a more than adequate
knowledge of information about epilepsy. Moreover, in case of seizure in the
classroom, first aid is to call an ambulance rather than administering rescue
drugs; b) teachers, who have had a real experience, represent the epileptic
student as more limited in the possibilities of getting married, having children,
finding a job, and practising a sport; c) teachers, who have had a student with
epilepsy don't report interpersonal relationships with his/her classmates as
being difficult. Moreover, they claim to have inadequate knowledge of the
educational strategies needed to integrate the epileptic student with his/her
classmates; d) there are some different answers for primary school teachers and
for secondary school teachers. CONCLUSIONS: Teachers demonstrate inaccurate
information about epilepsy, its impact in educational contexts and management of
seizures in the classroom. Also, critical areas have emerged indicating efforts
should focus on education, sharing the role of teacher, awareness and integration
in the class group.
PMID- 26437952
TI - Chitinophaga dinghuensis sp. nov., isolated from soil.
AB - A Gram-reaction-negative, aerobic, non-motile bacterial strain, DHOC24T, was
isolated from the forest soil of Dinghushan Biosphere Reserve, Guangdong
Province, PR China. Strain DHOC24T underwent a shape change during the course of
culture from long filamentous cells (10-30 * 0.4-0.5 MUm) at 2 days to
coccobacilli (0.5-1.0 * 0.7-1.0 MUm) at 15 days after inoculation. It grew
optimally at 28-33 degrees C and pH 6.5-7.5. The major quinone of strainDHOC24T
was MK-7, the main fatty acids were iso-C15 : 0, C16 : 1omega5c and iso-C17 : 0 3
OH and the DNA G+C content was 43.1 mol%. On the basis of 16S rRNA gene sequence
analysis, the strain was found to be affiliated with members of the genus
Chitinophaga, but was clearly separated from established species of the genus.
Strain DHOC24T was most closely related to Chitinophaga jiangningensis JN53T
(98.3 % 16S rRNA gene sequence similarity) and Chitinophaga terrae KP01T (97.9
%). DNA-DNA hybridization study showed relatively low relatedness values (32.1 %)
of strain DHOC24T with C. jiangningensis JN53T. The phenotypic, chemotaxonomic
and phylogenetic data showed that strain DHOC24T represents a novel species of
the genus Chitinophaga, for which the name Chitinophaga dinghuensis sp. nov. is
proposed. The type strain is DHOC24T ( = CGMCC 1.12995T = DSM 29821T).
PMID- 26437954
TI - Erratum to: congenital HCMV and assisted reproduction: why not use the chance for
primary screening?
PMID- 26437953
TI - Prognostic factors and genes associated with endometrial cancer based on gene
expression profiling by bioinformatics analysis.
AB - BACKGROUND: Endometrial cancer (EC) is the most prevalent malignancy worldwide.
Although several efforts had been made to explore the molecular mechanism
responsible for EC progression, it is still not fully understood. AIM OF THE
STUDY: To evaluate the clinical characteristics and prognostic factors of
patients with EC, and further to search for novel genes associated with EC
progression. METHODS: We recruited 328 patients with EC and analyzed prognostic
factors using Cox proportional hazard regression model. Further, a gene
expression profile of EC was used to identify the differentially expressed genes
(DEGs) between normal samples and tumor samples. Subsequently, Kyoto Encyclopedia
of Genes and Genomes pathway enrichment analysis ( http://www.genome.jp/kegg/ )
for DEGs were performed, and then protein-protein interaction (PPI) network of
DEGs as well as the subnetwork of PPI were constructed with plug-in, MCODE by
mapping DEGs into the Search Tool for the Retrieval of Interacting Genes
database. RESULTS: Our results showed that body mass index (BMI), hypertension,
myometrial invasion, pathological type, and Glut4 positive expression were
prognostic factors in EC (P < 0.05). Bioinformatics analysis showed that
upregulated DEGs were associated with cell cycle, and downregulated DEGs were
related to MAPK pathway. Meanwhile, PPI network analysis revealed that
upregulated CDK1 and CCNA2 as well as downregulated JUN and FOS were listed in
top two nodes with high degrees. CONCLUSIONS: Patients with EC should be given
more focused attentions in respect of pathological type, BMI, hypertension, and
Glut4-positive expression. In addition, CDK1, CCNA2, JUN, and FOS might play
important roles in EC development.
PMID- 26437955
TI - Predictors for a successful external cephalic version: a single centre
experience.
AB - PURPOSE: The external cephalic version (ECV) is one of the options patients
presenting with a breech pregnancy should be offered. Various fetal, maternal and
other predictors for a successful ECV have been published in the past. METHODS:
This is a retrospective multivariate analysis of our ECV patient database at the
Department of Obstetrics and Gynaecology at the University Hospital Ulm. In an
outpatient setting, patients with fetal breech position were routinely offered an
ECV attempt after 36 weeks of gestation if the patient was willing to consent.
Contraindications for ECV were placental abruption, placenta praevia, uterus
malformations, regular contractions, premature rupture of membranes, and non
reassuring fetal heart rate patterns. RESULTS: From January 1st 2010 to July 31st
2013, 444 patients with a minimum of 36 weeks gestational age (i.e. >35 + 6
weeks) attended our clinic with a breech presentation. Of those 118 had an ECV
attempt and an extended ultrasound examination within 21 days. In 33 patients the
procedure was successful (success rate 28 %). A multivariate binary logistic
regression analysis revealed that an increased Amniotic Fluid Index (AFI; p <
0.001), at least one prior vaginal delivery (p = 0.002) or a high estimated fetal
weight (p = 0.045) were significant independent predictors for a successful ECV.
In our series no delivery occurred within 48 h after the ECV. CONCLUSIONS: An ECV
is a safe procedure. ECV should be offered as an option for the mother-to-be on
the basis of an informed consent. Identified fetal and maternal factors can help
to estimate the chances of success and in particular multi-parity and increased
amniotic fluid seem to be associated with successful ECV.
PMID- 26437956
TI - Double-balloon catheter and sequential vaginal prostaglandin E2 versus vaginal
prostaglandin E2 alone for induction of labor after previous cesarean section.
AB - PURPOSE: To evaluate the efficacy of inducing labor using a double-balloon
catheter and vaginal prostaglandin E2 (PGE2) sequentially, in comparison with
vaginal PGE2 alone after previous cesarean section. METHODS: A total of 264
pregnant women with previous cesarean section undergoing labor induction at term
were included in this prospective multicentre cohort study. Induction of labor
was performed either by vaginal PGE2 gel or double-balloon catheter followed by
vaginal PGE2. The primary outcome measure was the cesarean section rate. RESULTS:
The cesarean section rate was 37 % without any statistically significant
difference between the two groups (PGE2: n = 41, 37 % vs. balloon catheter/PGE2:
n = 41, 42 %; P = 0.438). The median (range) number of applications of PGE2 [2 (1
10) versus 1 (0-8), P < 0.001] and the total amount of PGE2 used in median
(range) mg [2 (1-15) vs. 1 (0-14), P = 0.001] was less in the balloon
catheter/PGE2 group. Factors significantly increasing risk for cesarean section
were "no previous vaginal delivery" (OR 5.391; CI 2.671-10.882) and "no oxytocin
augmentation during childbirth" (OR 2.119; CI 1.215-3.695). CONCLUSIONS: The
sequential application of double-balloon catheter and vaginal PGE2 is as
effective as the sole use of vaginal PGE2 with less applications and total amount
of PGE2.
PMID- 26437957
TI - Comparison of citalopram and venlafaxine's role in treating sleep disturbances in
menopausal women, a randomized, double-blind, placebo-controlled trial.
AB - INTRODUCTION: Sleep disturbance is a common complaint in postmenopausal women.
Few studies compared symptom improvement taking antidepressants versus placebo.
This study aims to evaluate the efficacy of venlafaxine and Citalopram compared
to placebo in treatment of sleep disturbance in healthy postmenopausal women.
METHOD: This randomized, double-blind, placebo-controlled clinical trial was
conducted in three groups of 20 postmenopausal women. The patients took
venlafaxine 75 mg/daily (group I) or citalopram 20 mg/d (group II) or placebo
(group III). Each patient filled Pittsburgh sleep quality index (PSQI) and
Pittsburgh and Beck depression questionnaires. The frequency of hot flashes in a
day and its severity were measured through diaries. Somatic symptoms and adverse
side effects were evaluated. Follow-up visit was conducted after 3 months. The
prior and the later results were compared. RESULTS: The PSQI scores in three
placebo, venlafaxine, and citalopram groups before treatment were 14.25 +/- 3.85,
11.55 +/- 3.96, and 13.50 +/- 3.56, respectively (p = 0.076). These values after
treatment reached 9.95 +/- 5.07, 8 +/- 3.06, and 6.95 +/- 1.84, respectively.
PSQI score in citalopram and venlafaxine group was not significantly different (p
= 0.19) but the score in both groups was significantly lower compared with
placebo group after treatment (p = 0.01). The frequency of hot flashes in a day
was reduced significantly by both citalopram and venlafaxine (p < 0.05), although
it was more reduced by citalopram than venlafaxine (p = 0.03). Severity of hot
flashes in both venlafaxine and citalopram was significantly lower in comparison
with placebo group (p = 0.02), and there was no significant difference between
two drugs, though (p = 0.84). Beck score decreased more in venlafaxine group in
comparison with other groups but it did not reach significant (p = 0.06).
CONCLUSION: Citalopram and venlafaxine are equally more effective than placebo in
reducing sleep disturbance and severity of hot flashes, while citalopram is more
effective in reducing frequency of hot flashes than venlafaxine. Meanwhile,
venlafaxine is more effective than citalopram in treatment of depression in
postmenopausal women. TRIAL REGISTRATION: Iranian Registry of Clinical Trials
201210152576N6.
PMID- 26437958
TI - External quality assessment for acid fast bacilli smear microscopy in eastern
part of Ethiopia.
AB - BACKGROUND: External quality assessment (EQA) of sputum smear microscopy is
essential and indispensable component of any tuberculosis program. This study
assessed the EQA of acid fast bacilli (AFB) smear microscopy through onsite
evaluation, blinded rechecking and panel test. A one year study was conducted on
eight health institution laboratories from December 2011 to December 2012. Onsite
evaluation, blinded rechecking and panel tests were used to collect data. Data
were analyzed using SPSS version 16. Sensitivity, specificity, predictive values,
and proportions of false readings were calculated. The level of agreement was
measured using Kappa (kappa) value. RESULTS: Problems observed during onsite
evaluation include shortages of materials, disinfectant, and poor storage and
working condition. A total of 578 slides were collected for blinded rechecking,
of which 102 (17.6%) were reported as positive by peripheral laboratories. The
panel test revealed an overall error of 17 (25.25%) of which 14 (17.5%) were
minor errors [low false negative 6 (7.5%) and low false positive 8 (10%)], and 3
(3.75%) were major errors (high false positive). The sensitivity, specificity,
positive predictive values (PPV) and negative predictive values (NPV) of the
peripheral laboratories were 83.5, 97.8, 91.7, and 95.7, respectively. The false
readings at the peripheral laboratories were 32 (5.5%). Agreement on reading the
slides was observed on 546 (94.5%) slides (K = 0.84, SE = 0.054). CONCLUSIONS:
Lack of reagents, supplies, favorable working environment and AFB related
technical problems were identified in the peripheral laboratories. High false
negative error was found to be the predominant major error. A continuous and
strong EQA scheme should be implemented to avoid reporting errors and produce
quality sputum results.
PMID- 26437959
TI - The biogeographic origin of a radiation of trees in Madagascar: implications for
the assembly of a tropical forest biome.
AB - BACKGROUND: Madagascar's rain forests are characterized by extreme and uneven
patterns of species richness and endemicity, the biogeographic and evolutionary
origins of which are poorly understood. METHODS: Here we use a time-calibrated
phylogeny of a dominant group of trees in Madagascar's eastern rain forests,
Canarium, and related Burseraceae (Canarieae), to test biogeographic hypotheses
regarding the origin and radiation of the flora of this unique biome. RESULTS:
Our findings strongly support the monophyly of Malagasy Canarium, suggesting that
this clade represents a previously undocumented in situ radiation. Contrary to
expectations of dispersal from Africa during the Oligocene, concurrent with the
formation of Madagascar's rain forest biome, our analyses support a late Miocene
origin for Malagasy Canarium, probably by long distance dispersal from Southeast
Asia. DISCUSSION: Our study illustrates the importance of considering long
distance dispersal as a viable explanation for clades with pantropical
distributions diversifying subsequent to the Oligocene, and it highlights the
formation of the Indo-Australian Archipelago and associated fast-moving
equatorial surface currents, suggesting an under-appreciated evolutionary link
among tropical centers of endemism. CONCLUSIONS: We postulate that the relatively
recent establishment and radiation of Canarium in Madagascar may have been
facilitated by the highly stochastic climates associated with these forest
ecosystems.
PMID- 26437960
TI - Systematic literature review of determinants of sedentary behaviour in older
adults: a DEDIPAC study.
AB - BACKGROUND: Older adults are the most sedentary segment of society and high
sedentary time is associated with poor health and wellbeing outcomes in this
population. Identifying determinants of sedentary behaviour is a necessary step
to develop interventions to reduce sedentary time. METHODS: A systematic
literature review was conducted to identify factors associated with sedentary
behaviour in older adults. Pubmed, Embase, CINAHL, PsycINFO and Web of Science
were searched for articles published between 2000 and May 2014. The search
strategy was based on four key elements: (a) sedentary behaviour and its
synonyms; (b) determinants and its synonyms (e.g. correlates, factors); (c) types
of sedentary behaviour (e.g. TV viewing, sitting, gaming) and (d) types of
determinants (e.g. environmental, behavioural). Articles were included in the
review if specific information about sedentary behaviour in older adults was
reported. Studies on samples identified by disease were excluded. Study quality
was rated by means of QUALSYST. The full review protocol is available from
PROSPERO (PROSPERO 2014: CRD42014009823). The analysis was guided by the socio
ecological model framework. RESULTS: Twenty-two original studies were identified
out of 4472 returned by the systematic search. These included 19 cross-sectional,
2 longitudinal and 1 qualitative studies, all published after 2011. Half of the
studies were European. The study quality was generally high with a median of 82 %
(IQR 69-96 %) using Qualsyst tool. Personal factors were the most frequently
investigated with consistent positive association for age, negative for
retirement, obesity and health status. Only four studies considered environmental
determinants suggesting possible association with mode of transport, type of
housing, cultural opportunities and neighbourhood safety and availability of
places to rest. Only two studies investigated mediating factors. Very limited
information was available on contexts and sub-domains of sedentary behaviours.
CONCLUSION: Few studies have investigated determinants of sedentary behaviour in
older adults and these have to date mostly focussed on personal factors, and
qualitative studies were mostly lacking. More longitudinal studies are needed as
well as inclusion of a broader range of personal and contextual potential
determinants towards a systems-based approach, and future studies should be more
informed by qualitative work.
PMID- 26437961
TI - Influence of social experiences in shaping perceptions of the Ebola virus among
African residents of Hong Kong during the 2014 outbreak: a qualitative study.
AB - INTRODUCTION: The outbreak of Ebola virus disease (EVD) in Africa in 2014
attracted worldwide attention. Because of the high mortality rate, marginalised
social groups are vulnerable to disease-associated stigmatisation and
discrimination, according to the literature. In Hong Kong, ethnic minorities such
as Africans are often disadvantaged groups because of their low position in the
social hierarchy. In 2011, approximately 1700 Africans were residing in Hong
Kong. Their overseas experiences during the EVD outbreak were not well
documented. Therefore, this study investigated the EVD-associated stigmatisation
experiences of African residents of Hong Kong with chronic illnesses, and how
these experiences shaped their perceptions of EVD. METHODS: A qualitative design
with 30 in-depth semistructured interviews was conducted with chronically ill
African residents of Hong Kong. RESULTS: The interview data showed that the
sampled Africans often experienced stigmatisation in their workplaces and in the
community during the EVD outbreak. Their experiences of EVD-associated stigma
were correlated to the embedded social and cultural values regarding ethnic
minorities in Hong Kong. These experiences of being stigmatised shaped the
perceptions of the Africans of EVD, leading them to view EVD as shameful and
horrifying. They also perceived EVD as retribution and was introduced by
Westerners. The participants' perceptions of EVD influenced their responses to
and behaviour towards EVD, which may have posed potential threats to Hong Kong's
public health. CONCLUSIONS: The EVD outbreak was not the only cause of the
participants' stigmatisation; rather, their EVD-associated experiences were a
continuation and manifestation of the embedded social and cultural values
regarding ethnic minorities in Hong Kong. The experiences of being stigmatised
shaped the participants' perceptions of EVD. Because of their marginalised social
position and isolation from the main community, the participants had extremely
limited access to reliable information about EVD. As a result, they used their
own cultural beliefs to understand EVD, which might have ultimately influenced
their health behaviours. The experiences of the participants showed that ethnic
minorities in Hong Kong were in need of more culturally responsive social and
health care support to obtain reliable information about the nature of and
preventive measures against EVD.
PMID- 26437962
TI - Activating PI3Kdelta mutations in a cohort of 669 patients with primary
immunodeficiency.
AB - The gene PIK3CD codes for the catalytic subunit of phosphoinositide 3-kinase
delta (PI3Kdelta), and is expressed solely in leucocytes. Activating mutations of
PIK3CD have been described to cause an autosomal dominant immunodeficiency that
shares clinical features with common variable immunodeficiency (CVID). We
screened a cohort of 669 molecularly undefined primary immunodeficiency patients
for five reported mutations (four gain-of-function mutations in PIK3CD and a loss
of function mutation in PIK3R1) using pyrosequencing. PIK3CD mutations were
identified in three siblings diagnosed with CVID and two sporadic cases with a
combined immunodeficiency (CID). The PIK3R1 mutation was not identified in the
cohort. Our patients with activated PI3Kdelta syndrome (APDS) showed a range of
clinical and immunological findings, even within a single family, but shared a
reduction in naive T cells. PIK3CD gain of function mutations are more likely to
occur in patients with defective B and T cell responses and should be screened
for in CVID and CID, but are less likely in patients with a pure B
cell/hypogammaglobulinaemia phenotype.
PMID- 26437963
TI - Web-Based Malignancy Risk Estimation for Thyroid Nodules Using Ultrasonography
Characteristics: Development and Validation of a Predictive Model.
AB - BACKGROUND: To establish a practical and simplified method for analyzing thyroid
nodules in a clinical setting, the development of a new practical prediction
model was required. This study aimed to construct and validate a simple and
reliable web-based predictive model using the ultrasonography characteristics of
thyroid nodules to stratify the risk of malignancy. METHODS: To analyze
ultrasonography images, radiologists were asked to assess thyroid nodules
according to the following criteria: internal content, echogenicity of the solid
portion, shape, margin, and calcifications. Multivariate logistic regression was
performed to predict whether nodules were diagnosed as malignant or benign. The
developmental data set included 849 nodules (January-June 2003). The validation
set included different data (n = 453, June 2008-February 2009). RESULTS:
Ultrasonography features, including solid content, taller-than-wide shape,
spiculated margin, ill-defined margin, hypoechogenicity, marked hypoechogenicity,
microcalicifications, and rim calcifications, were selected as predictors for
malignant nodules in the development set. A 14-point risk scoring system was
developed. Malignancy risk ranged from 3.8% to 97.4%, and the risk of malignancy
was positively associated with increases in risk scores. The areas under the
receiver operating characteristic curve of the development and validation sets
were 0.903 and 0.897, respectively. CONCLUSION: A simple and reliable web-based
predictive model was designed using ultrasonography characteristics to stratify
thyroid nodules according to the probability of malignancy.
PMID- 26437964
TI - Towards in vivo estimation of reaction kinetics using high-throughput
metabolomics data: a maximum likelihood approach.
AB - BACKGROUND: High-throughput assays such as mass spectrometry have opened up the
possibility for large-scale in vivo measurements of the metabolome. This data
could potentially be used to estimate kinetic parameters for many metabolic
reactions. However, high-throughput in vivo measurements have special properties
that are not taken into account in existing methods for estimating kinetic
parameters, including significant relative errors in measurements of metabolite
concentrations and reaction rates, and reactions with multiple substrates and
products, which are sometimes reversible. A new method is needed to estimate
kinetic parameters taking into account these factors. RESULTS: A new method,
InVEst (In Vivo Estimation), is described for estimating reaction kinetic
parameters, which addresses the specific challenges of in vivo data. InVEst uses
maximum likelihood estimation based on a model where all measurements have
relative errors. Simulations show that InVEst produces accurate estimates for a
reversible enzymatic reaction with multiple reactants and products, that
estimated parameters can be used to predict the effects of genetic variants, and
that InVEst is more accurate than general least squares and graphic methods on
data with relative errors. InVEst uses the bootstrap method to evaluate the
accuracy of its estimates. CONCLUSIONS: InVEst addresses several challenges of in
vivo data, which are not taken into account by existing methods. When data have
relative errors, InVEst produces more accurate and robust estimates. InVEst also
provides useful information about estimation accuracy using bootstrapping. It has
potential applications of quantifying the effects of genetic variants, inference
of the target of a mutation or drug treatment and improving flux estimation.
PMID- 26437965
TI - Kinetics and model development for enzymatic synthesis of fructo-oligosaccharides
using fructosyltransferase.
AB - Experimental investigations were made to synthesize fructo-oligosaccharides (FOS)
from sucrose using fructosyltransferase. The influence of various parameters such
as temperature (45-55 degrees C), pH (4-5), initial sucrose concentration (ISC:
300-500 g/L) and enzyme concentration (4-32 U/mL) were varied. A maximum FOS
yield of 60% was observed at ISC 500 g/L, pH 4.5 with enzyme activity 32 U/mL and
at 55 degrees C. It was confirmed that 1-kestose (tri-) was the major product of
FOS as compared to nystose (tetra-) and fructosylnystose (penta-saccharides).
Further, the reaction rate increases with increase in temperature. From separate
sets of experiments, it was observed that FOS formation was affected by glucose
inhibition. Apart from the increase in the rate of FOS formation with increasing
enzyme activity, the final values of FOS yield increase though till 16 U/mL and
thereafter attain plateau. A kinetic model was also developed, based on Michaelis
Menten kinetics, and a five-step ten-parameter model, including glucose
inhibition, was obtained. Model was solved using COPASI((r)) (version 4.8) solver
for kinetic parameter estimations followed by time course simulations.
PMID- 26437966
TI - Laccases for biorefinery applications: a critical review on challenges and
perspectives.
AB - Modern biorefinery concepts focus on lignocellulosic biomass as a feedstock for
the production of next generation biofuels and platform chemicals. Lignocellulose
is a recalcitrant composite consisting of several tightly packed components which
are stuck together by the phenolic polymer lignin hampering the access to the
carbohydrate compounds of biomass. Certain saprophytic organisms are able to
degrade lignin by the use of an enzymatic cocktail. Laccases have been found to
play a major role during lignin degradation and have therefore been intensively
researched with regard to potential applications for biomass processing. Within
this review, we go along the process chain of a third generation biorefinery and
highlight the process steps which could benefit from laccase applications.
Laccases can assist the pretreatment of biomass and promote the subsequent
enzymatic hydrolysis of cellulose by the oxidative modification of residual
lignin on the biomass surface. In combination with mediator molecules laccases
are often reported being able to catalyze the depolymerization of lignin. Studies
with lignin model compounds confirm the chemical possibility of a laccase
catalyzed cleavage of lignin bonds, but the strong polymerization activity of
laccase counters the decomposition of lignin by repolymerizing the degradation
products. Therefore, it is a key challenge to shift the catalytic performance of
laccase towards lignin cleavage by optimizing the process conditions. Another
field of application for laccases is the detoxification of biomass hydrolyzates
by the oxidative elimination of lignin-derived phenolics which inhibit hydrolytic
enzymes and are toxic for fermentation organisms. This review critically
discusses the potential applications for laccases in biorefinery processes and
emphasizes the challenges and perspectives which go along with the use of this
enzyme for the technical utilization of lignocellulose.
PMID- 26437968
TI - The tricky charm of the radial access.
PMID- 26437967
TI - A cross-sectional analysis of the relationship between tobacco and alcohol outlet
density and neighbourhood deprivation.
AB - BACKGROUND: There is a strong socio-economic gradient in both tobacco-and alcohol
related harm. One possible factor contributing to this social gradient may be
greater availability of tobacco and alcohol in more socially-deprived areas. A
higher density of tobacco and alcohol outlets is not only likely to increase
supply but also to raise awareness of tobacco/alcohol brands, create a
competitive local market that reduces product costs, and influence local social
norms relating to tobacco and alcohol consumption. This paper examines the
association between the density of alcohol and tobacco outlets and neighbourhood
level income deprivation. METHODS: Using a national tobacco retailer register and
alcohol licensing data this paper calculates the density of alcohol and tobacco
retail outlets per 10,000 population for small neighbourhoods across the whole of
Scotland. Average outlet density was calculated for neighbourhoods grouped by
their level of income deprivation. Associations between outlet density and
deprivation were analysed using one way analysis of variance. RESULTS: There was
a positive linear relationship between neighbourhood deprivation and outlets for
both tobacco (p <0.001) and off-sales alcohol (p <0.001); the most deprived
quintile of neighbourhoods had the highest densities of both. In contrast, the
least deprived quintile had the lowest density of tobacco and both off-sales and
on-sales alcohol outlets. CONCLUSIONS: The social gradient evident in alcohol and
tobacco supply may be a contributing factor to the social gradient in alcohol-
and tobacco-related disease. Policymakers should consider such gradients when
creating tobacco and alcohol control policies. The potential contribution to
public health, and health inequalities, of reducing the physical availability of
both alcohol and tobacco products should be examined in developing broader supply
side interventions.
PMID- 26437969
TI - Upper-extremity dysfunction following transradial percutaneous procedures: an
overlooked and disregarded complication?
PMID- 26437970
TI - Revealing the impact of local access-site complications and upper extremity
dysfunction post transradial percutaneous coronary procedures.
AB - OBJECTIVES: Little is known about local access-site complications and upper
extremity dysfunction after transradial percutaneous coronary procedures (TR
PCP). This systematic review study aimed to summarise the current knowledge on
the incidences of access-site complications and upper extremity dysfunction after
TR-PCP. METHODS: Two independent, trained investigators searched MEDLINE, EMBASE
and CENTRAL for eligible studies published before 1 January 2015. Also, they hand
searched the conference proceedings of the annual scientific sessions of the
American College of Cardiology, the American Heart Association, European Society
of Cardiology, and the Trans-catheter Cardiovascular Therapeutics. Inclusion
criteria were cohort studies and clinical trials discussing the incidence of
access-site complications and upper extremity function after transradial
percutaneous coronary intervention (TR-PCI) and/or transradial coronary
angiography (TR-CAG) as endpoints. RESULTS: 176 articles described access-site
complications. The incidence is up to 9.6 %. Fourteen articles described upper
extremity dysfunction, with an incidence of up to 1.7 %. Upper extremity
dysfunction was rarely investigated, hardly ever as primary endpoint, and if
investigated not thoroughly enough. CONCLUSION: Upper extremity dysfunction in TR
PCP has never been properly investigated and is therefore underestimated. Further
studies are needed to investigate the magnitude, prevention and best treatment of
upper extremity dysfunction. Optimising TR-PCP might be achieved by using slender
techniques, detection of upper extremity dysfunction and early referral to a hand
rehabilitation centre.
PMID- 26437971
TI - An Autocatalytic System of Photooxidation-Driven Substitution Reactions on a
Fe(II)4L6 Cage Framework.
AB - The functions of life are accomplished by systems exhibiting nonlinear kinetics:
autocatalysis, in particular, is integral to the signal amplification that allows
for biological information processing. Novel synthetic autocatalytic systems
provide a foundation for the design of artificial chemical networks capable of
carrying out complex functions. Here we report a set of Fe(II)4L6 cages
containing BODIPY chromophores having tuneable photosensitizing properties.
Electron-rich anilines were observed to displace electron-deficient anilines at
the dynamic-covalent imine bonds of these cages. When iodoaniline residues were
incorporated, heavy-atom effects led to enhanced (1)O2 production. The
incorporation of (methylthio)aniline residues into a cage allowed for the design
of an autocatalytic system: oxidation of the methylthio groups into sulfoxides
make them electron-deficient and allows their displacement by iodoanilines,
generating a better photocatalyst and accelerating the reaction.
PMID- 26437972
TI - The association between pelvic girdle pain and sick leave during pregnancy; a
retrospective study of a Norwegian population.
AB - BACKGROUND: The incidence of pelvic girdle pain (PGP) in pregnancy is wide ranged
depending on definition, the utilised diagnostic means, and the design of the
studies. PGP during pregnancy has negative effects on activities of daily living
and causes long sick leave, which makes it a major public health issue. Our
objectives were to explore the frequency of sick leave in pregnancy due to PGP,
assess the relationship between different types of pain-related activities of
daily living, examine physical workload, type of work in relation to sick leave,
and to explore factors that make women less likely to take sick leave for PGP.
METHODS: All women giving birth at the maternity ward of Stavanger University
Hospital, Norway, were asked to participate and complete a questionnaire on
demographic features, PGP, pain-related activities of daily living, sick leave in
general and for PGP, frequency of exercising before and during pregnancy.
Drawings of pelvic girdle and low back area were used for the localization of
pain. PGP intensity was then rated retrospectively on a numerical rating scale.
Non-parametric tests, multinomial logistic regression and sequential linear
regression analysis were used in the statistical analysis. RESULTS: PGP is a
frequent and major cause of sick leave during pregnancy among Norwegian women,
which is also reflected in activities of daily living as measured with scores on
all Oswestry disability index items. In the multivariate analysis of factors
related to sick leave and PGP we found that work satisfaction, problems with
lifting and sleeping, and pain intensity were risk factors for sick leave. In
addition, women with longer education, higher work satisfaction and fewer
problems with sitting, walking and standing, were less likely to take sick leave
in pregnancy, despite the same pain intensity as women being on sick leave.
CONCLUSIONS: A coping factor in pregnant women with PGP was discovered, most
likely dependant on education, associated with work situation and/or work
posture, which decreases sick leave. We recommend these issues to be further
examined in a prospective longitudinal study since it may have important
implications for sick leave frequency during pregnancy.
PMID- 26437973
TI - Recent research progress with phospholipase C from Bacillus cereus.
AB - Phospholipase C (PLC) catalyzes the hydrolysis of phospholipids to produce
phosphate monoesters and diacylglycerol. It has many applications in the
enzymatic degumming of plant oils. PLC Bc , a bacterial PLC from Bacillus cereus,
is an optimal choice for this activity in terms of its wide substrate spectrum,
high activity, and approved safety. Unfortunately, its large-scale production and
reliable high-throughput screening of PLC Bc remain challenging. Herein, we
summarize the research progress regarding PLC Bc with emphasis on the screening
methods, expression systems, catalytic mechanisms and inhibitor of PLC Bc . This
review hopefully will inspire new achievements in related areas, to promote the
sustainable development of PLC Bc and its application.
PMID- 26437975
TI - Prevention of post-operative recurrence in Crohn's disease. Are we ready for a
treat-to-target strategy?
PMID- 26437974
TI - Immunomodulatory effect of hypertonic saline in hemorrhagic shock.
AB - Multiple organ dysfunction syndrome (MODS) and nosocomial infection following
trauma-hemorrhage are among the most important causes of mortality in hemorrhagic
shock patients. Dysregulation of the immune system plays a central role in MODS
and a fluid having an immunomodulatory effect could be advantageous in
hemorrhagic shock resuscitation. Hypertonic saline (HS) is widely used as a
resuscitation fluid in trauma-hemorrhagic patients. Besides having beneficial
effects on the hemodynamic parameters, HS has modulatory effects on various
functions of immune cells such as degranulation, adhesion molecules and cytokines
expression, as well as reactive oxygen species production. This article reviews
clinical evidence for decreased organ failure and mortality in hemorrhagic shock
patients resuscitated with HS. Despite promising results in animal models,
results from pre-hospital and emergency department administration in human
studies did not show improvement in survival, organ failure, or a reduction in
nosocomial infection by HS resuscitation. Further post hoc analysis showed some
benefit from HS resuscitation for severely-injured patients, those who received
more than ten units of blood by transfusion, patients who underwent surgery, and
victims of traumatic brain injury. Several reasons are suggested to explain the
differences between clinical and animal models.
PMID- 26437976
TI - Impact of endoscopic monitoring in postoperative Crohn's disease patients already
receiving pharmacological prevention of recurrence.
AB - BACKGROUND: Current guidelines address the initiation of treatment to prevent
postoperative recurrence (PR) after ileo-cecal resection in Crohn's disease (CD),
but appropriate management of postoperative CD patients who are already receiving
treatment to prevent PR is yet to be defined. Usefulness of endoscopic monitoring
in this scenario remains uncertain. AIMS: To evaluate the usefulness of endoscopy
based management of postoperative CD patients who are already under
pharmacological prevention of PR. METHODS: Retrospective review of clinical
outcome of all CD patients with ileo-cecal resection who underwent postoperative
colonoscopy between 2004 and 2013 at our centre. Postoperative endoscopic
findings were classified as no endoscopic recurrence (Rutgeerts i0-i1) or
endoscopic recurrence (Rutgeerts i2-i4). Patients with endoscopic recurrence were
classified as "endoscopy-based management (EBM)" if treatment step-up after
endoscopy, or "non EBM (N-EBM)". Clinical recurrence was considered if re
operation, CD related hospitalization or treatment change. Time until clinical
recurrence or the end of the follow up was considered. RESULTS: One hundred sixty
six patients initially identified. One hundred twenty nine (77%) under
pharmacological prevention of PR at the time of colonoscopy were analyzed: 34%
were receiving aminosalicylates, 50% thiopurines, 11% anti-TNF, 5% combo.
Colonoscopy showed endoscopic recurrence in 57% of patients; those with N-EBM
were more likely to have clinical recurrence than patients with EBM along the
follow up (p = 0.01). Conclussions: Endoscopic monitoring could be useful in
postoperative CD patients also in patients already receiving pharmacological
treatment to prevent PR.
PMID- 26437977
TI - Efficacy and safety of simeprevir in combination with peginterferon and ribavirin
for patients with hepatitis C genotype 1 infection: a meta-analysis of randomized
trials.
AB - BACKGROUND AND AIM: A simeprevir (SMV)-based regimen has shown promising results
in treating chronic hepatitis C virus (HCV) infection. This meta-analysis aimed
to assess the efficacy and safety of simeprevir for treating HCV genotype 1
infection. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of
Controlled Trials were searched, along with the reference lists of retrieved
articles. The meta-analysis only included randomized controlled trials (RCTs)
that compared the efficacy and safety of addition of SMV to peginterferon
(PegIFN) and ribavirin (RBV) (triple regimen) with PegIFN/RBV alone (dual
regimen) in treating chronic HCV genotype 1 infection. RESULTS: A total of seven
RCTs involving 2,301 patients were included. The triple regimen had a higher
pooled sustained virologic response (SVR) rate [odds ratio (OR) = 4.57; 95%
confidence interval (CI): 3.34-6.27; p < 0.001)] and lower pooled relapse rate
[relative risk (RR) = 0.41; 95% CI: 0.33-0.50; p < 0.001] than the dual regimen
had. The pooled incidence of adverse events (AEs) was comparable between the two
regimens (RR = 1.01; 95% CI: 0.99-1.03; p = 0.339), whereas the incidence of
serious AEs in the triple regimen was lower (RR = 0.7; 95% CI: 0.50-0.98; p <
0.05). CONCLUSIONS: The meta-analysis demonstrates that the addition of SMV to
pegIFN and RBV is effective and well-tolerated in treating chronic HCV genotype 1
infection, with a low incidence of AEs.
PMID- 26437978
TI - Screening of enzymatic synthesis and expression of Lewis determinants in human
colorectal carcinoma.
AB - BACKGROUND: Although colorectal carcinogenesis has been intensively studied, the
published investigations do not provide a consistent description of how different
carbohydrate determinants of colorectal epithelium are modified in colorectal
cancer (CRC). OBJECTIVE: This study is an attempt to characterize the terminal
fucosylation steps responsible for the synthesis of mono- Le(a)/Le(x)- and
difucosylated -Le(b)/Le(y)- Lewis antigens in healthy and tumour CRC tissue.
METHODS: An immunohistochemical study of Lewis antigens' expression was
undertaken, along with screening of the fucosyltransferase (FT) activities
involved in their synthesis, on healthy and tumour samples from 18 patients
undergoing CRC. RESULTS: Analysis of alpha(1,2/3/4)FT activities involved in the
sequential fucosylation of cores 1 and 2 showed significant increases in tumour
tissue. Expressed as microU/mg and control vs. tumour activity (pfrom Wilcoxon's
test), the FT activities for Le(a)/Le(b) synthesis were: lacto-N-biose
alpha(1,2)/alpha(1,4)FT, 65.4 +/- 19.0 vs. 186 +/- 35.1 (p< 0.005); lacto-N
fucopentaose 1 alpha(1,4)FT, 64.9 +/- 11.9 vs. 125.4 +/- 20.7 (p< 0.005); Le(a)
alpha(1,2)FT, 56.2 +/- 7.2 vs. 130.5 +/- 15.6 (p< 0.001). Similarly, for
Le(x)/Le(y) synthesis were: N-acetyllactosamine alpha(1,2)-/alpha(1,3)FT, 53.4 +/
12.2 vs. 108.1 +/- 18.9 (p< 0.001); 2'-Fucosyl-N-acetyllactosamine alpha(1,3)FT,
61.3 +/- 10.7 vs. 126.4 +/- 22.9 (p< 0.001); 2'-Fucosyllactose alpha(1,3)FT, 38.9
+/- 10.9 vs. 143.6 +/- 28.9 (p< 0.001); 2'-Methyllactose alpha(1,3)FT, 30.9 +/-
4.8 vs. 66.1 +/- 8.1 (p< 0.005); and Le(x) alpha(1,2)FT, 54.3 +/- 11.9 vs. 88.2
+/- 14.4 (p< 0.001). Immunohistochemical Le(y) expression was increased (p< 0.01
according to Wilcoxon's test) in tumour tissue, with 84.6% of specimens being
positive: 7.7% weak, 15.4% moderate and 61.5% high intensity. CONCLUSIONS:
Results suggest the activation of the biosynthesis pathways of mono- and
difucosylated Lewis histo-blood antigens in tumour tissue from CRC patients,
leading to the overexpression of Le(y), probably at the expense of Le(x).
PMID- 26437980
TI - Impact of the age of diagnosis on the natural history of ulcerative colitis.
AB - BACKGROUND: Ulcerative colitis (UC) has a recognized phenotypic heterogeneity.
Some studies suggest that age at diagnosis may influence features and natural
history of the disease. AIM: This study aimed to compare patients', disease's and
treatment's features between Portuguese patients diagnosed before and after the
age of 40-years-old. METHODS: Retrospective single-center study that included 310
patients with UC, divided in two groups: Those diagnosed before the age of 40
years-old (early onset UC) and those diagnosed later than that (late onset UC).
In each group features of the patients (gender, family history, smoking), of the
disease (duration, extension, severity, clinical course, hospitalization,
extraintestinal manifestations), and of treatment (oral aminosalicylates,
systemic steroids or immunomodulators) were analyzed. Statistical analysis was
performed using SPSSv22.0. Univariate and multivariate analyses were performed to
assess factors associated with early and late onset UC. RESULTS: From the
analyzed patients, 207 had UC diagnosed before the age of 40 years old (43.5%
men; mean age at diagnosis 29.4 +/- 6.9 years) and 103 were diagnosed after that
age (61.2% men; mean age at diagnosis 51.8 +/- 8.1 years). In the group diagnosed
before 40 years old, female gender (p = 0.003), severe disease (p = 0.002),
chronic intermittent clinical course (p = 0.026), and hospitalizations (p =
0.001) were significantly more frequent. The use of oral aminosalicylates (p =
0.032), systemic steroids (p = 0.003) and immunomodulators (p = 0.012) were also
more common in the early onset UC group. No differences between groups were found
in family history, smoking, disease's extension, extraintestinal manifestations,
and use of biological agents. Multivariate analysis pointed early onset UC to be
significantly associated with female gender (odds ratio [OR], 1.77; 95%
confidence interval [CI], 1.08-2.91; p = 0.024), chronic intermittent symptoms
(OR, 2.34; 95% CI, 1.17-4.70; p = 0.016), and need of hospitalization (OR, 2.89;
95% CI, 1.46-5.72; p = 0.002). CONCLUSIONS: When diagnosed before the age of 40
years-old, UC preferably affects women and manifests as a more severe disease,
with more frequent hospitalizations and chronic intermittent symptoms. These
facts might have implications in planning timely and individualized future
therapeutic strategies.
PMID- 26437979
TI - Fully covered metal stents for the treatment of leaks after gastric and
esophageal surgery.
AB - OBJECTIVE: The use of fully covered metal stents (FCMS) for the treatment of
benign conditions is increasing. The aim of our study was to assess the efficacy
of FCMS in the management of post-operative leaks after gastric or esophageal
surgery. MATERIAL AND METHODS: During a three year period (2011-2013), patients
who underwent a surgery related with esophageal or gastric cancer and developed a
postoperative anastomotic leak treated with FCMS were prospectively included.
RESULTS: Fourteen patients were included (11 men, 3 women), with median age of 65
years. Placement of at least one stent was achieved in 13 patients (93% of
cases), with initial closure of the leak in 12 of these 13 cases (92.3%). A final
success (after removal of the stent) could be demonstrated in 9 cases (69.2%,
intention to treat analysis); stent failed only in one case (7.7%) and there were
3 patients (23.1%) not evaluated because death before stent retrieval (not
related with the endoscopic procedure). One stent were used in 9 cases (69.2%),
and two in 4 (30.8%). Migration was observed in two cases (15.3%). There were no
major complications related with the use of stents. There were no complications
related with retrieval. CONCLUSIONS: The placement of FCMS to achieve the leak
closure after esophageal or gastric surgery is an effective and probably safe
alternative feasible with minor risks.
PMID- 26437981
TI - Impaired esophageal motor function in eosinophilic esophagitis.
AB - Eosinophilic esophagitis is a chronic immunoallergic inflammatory disease of the
esophagus that represents a major cause of digestive morbidity among the
pediatric and young adult populations. Despite the fact that key symptoms in
adults include dysphagia and food impaction, many patients lack structural
changes in the esophagus to account for their complaints, which suggests the
presence of underlying motor disorders and esophageal distensibility impairment.
In the last few years the esophageal motility of these patients has been studied
using various approaches, most particularly high-resolution manometry, ambulatory
manometry, and impedance planimetry. This review focuses on the most relevant
findings and scientific evidence regarding esophageal motor disorders in
eosinophilic esophagitis.
PMID- 26437982
TI - Solitary fibrous tumor of the liver. Case report and review of the literature.
AB - Solitary fibrous tumor (SFT) is a rare mesenchymal tumor. Given its origin, it
can appear in almost any location. In the literature, only 50 cases of SFT in the
liver parenchyma have been reported. Despite its rarity, this entity should be
included in the differential diagnosis of liver masses. We report the first case
with imaging data from five years prior to diagnosis, which was treated by right
portal embolization and arterial tumor embolization, and subsequent liver
resection. We also present an exhaustive review of the cases described to date.
PMID- 26437984
TI - Spanish in international bibliography.
AB - Comments related to a review article about percutaneous gastrostomies written by
Lucendo et al. in REED.
PMID- 26437983
TI - Duodenal involvement by seminomatous tumors.
AB - Testicular germ cell tumors, though rare (1%), represent the most common neoplasm
among young men. Gastrointestinal involvement from these malignancies usually
presents as bowel obstruction and digestive bleeding, but their frequency is low
(5%). The patterns of this involvement are: infiltration from affected
retroperitoneal lymph nodes or, less frequently, by peritoneal seeding and direct
hematogenous spread. Particularly, infiltration of duodenum is also rare, though
its real frequency is not well defined. Moreover, the affinity for GI tract
differs among the histological types of GCT, being seminomatous tumors an
exceedingly unfrequent cause of duodenal infiltration. We herein present a recent
case in our institution of severe anemia due to gastrointestinal bleeding in the
context of giant retroperitoneal bulky metastatic mass infiltrating duodenum as
first manifestation of a testicular pure seminoma.
PMID- 26437985
TI - Synchronic gastric and pancreatic ductal adenocarcinoma. A case report.
AB - Simultaneous gastric and pancreatic ductal adenocarcinoma is an exceptional
situation with short literature review. The accumulated risk throughout life in
women is 0.8% for gastric cancer and 0.6% for pancreas cancer. We report a case
where both tumors are demonstrated. The patient was surgically intervened
removing both tumors and achieving total recovery, with no signs of tumor
recurrence after four months. This is to remind us that simultaneous tumors do
exist, especially when suggestive images of neoplasia appear in a patient
previously diagnosed of tumor in another location.
PMID- 26437986
TI - Mucinous hepatic cystic neoplasm: an uncommon cystic lesion in the liver.
AB - Invasive hepatic mucinous neoplasms, previously referred to as cystoadenomas, are
rare tumours of the liver. Many patients are asymptomatic and the lessions are
found incidentally. Tha aim of this paper is to present a clinic case about a
asymptomatic 78 years-old-man with a cystic neoplasm of the liver, founded
incidentanlly and treated by surgery.
PMID- 26437987
TI - Leiomyoma of the round ligament of the liver: report of one case.
AB - Tumoral conditions in the round ligament of the liver are very uncommon and
exhibit nonspecific manifestations, hence a high level of suspicion is necessary
for their diagnosis. We report the case of a 47-year-old female patient who
presented with abdominal pain for several months; imaging studies showed a lesion
of indeterminate nature likely connected with the falciform ligament, and only
intraoperative findings acknowledged the presence of an apparently benign tumor
in the round ligament of the liver, which biopsy confirmed. Following the
excision of the round ligament the patient had a favorable course. As this is a
pathologically benign lesion we deem its surgical management both advisable and
sufficient. However, because of its small prevalence and the scarcity of
literature involving this condition, further studies would be needed to provide
information on natural history, treatment, and long-term prognosis.
PMID- 26437988
TI - Sprue-like enteropathy due to olmesartan.
AB - A case of spue-like enteropathy due to olmesartan is reported to draw attention
to this disease, given the high frequency of use of this drug and the difficulty
of diagnosis if the entity if it is not known. In his journal one case was
published as Clinical Note in 2014 and we wish to emphasize the importance of
knowledge about this relatively new entity.
PMID- 26437989
TI - Choosing a Hyperacute Stroke Imaging Protocol for Proper Patient Selection and
Time Efficient Endovascular Treatment: Lessons from Recent Trials.
AB - Recently, several prospective randomized control trials regarding endovascular
treatment for patients with intracranial large artery occlusions causing acute
ischemic stroke have been successfully reported. Effort to minimize time delays
to endovascular treatment, patient selection and the use of retrievable stent
were important factors for the success of these trials. The inclusion and
exclusion criteria for each of these trials did include differences in imaging
protocols. In this review, we focus on the importance of baseline non-invasive
angiography prior to deciding endovascular treatment. Then imaging protocols are
described for each trial according to measurement of infarct volume and
collateral grading.
PMID- 26437990
TI - Patent Foramen Ovale and Stroke-Current Status.
AB - Patent foramen ovale (PFO) is growing in clinical interest because of a renewed
focus on embolic stroke of undetermined source (ESUS), the PFO attributable
fraction (the 10-point Risk of Paradoxical Embolism score), technical advances in
PFO diagnosis, and the emergence of endovascular device closure as a treatment
option. However, recent randomized controlled trials of the management of
patients with ESUS and PFO failed to demonstrate the superiority of closure over
medical treatment. The mechanisms of stroke other than paradoxical embolism may
be important in patients with ESUS and PFO. This paper reviews the current
understanding of the pathophysiology of stroke and therapeutic options in
patients with PFO and ESUS.
PMID- 26437992
TI - Stroke Connectome and Its Implications for Cognitive and Behavioral Sequela of
Stroke.
AB - Systems-based approaches to neuroscience, using network analysis and the human
connectome, have been adopted by many researchers by virtue of recent progress in
neuroimaging and computational technologies. Various neurological disorders have
been evaluated from a network perspective, including stroke, Alzheimer's disease,
Parkinson's disease, and traumatic brain injury. Until now, dynamic processes
after stroke and during recovery were investigated through multimodal
neuroimaging techniques. Many studies have shown disruptions in structural and
functional connectivity, including in large-scale neural networks, in patients
with stroke sequela such as motor weakness, aphasia, hemianopia, neglect, and
general cognitive dysfunction. A connectome-based approach might shed light on
the underlying mechanisms of stroke sequela and the recovery process, and could
identify candidates for individualized rehabilitation programs. In this review,
we briefly outline the basic concepts of structural and functional connectivity,
and the connectome. Then, we explore current evidence regarding how stroke
lesions cause changes in connectivity and network architecture parameters.
Finally, the clinical implications of perspectives on the connectome are
discussed in relation to the cognitive and behavioral sequela of stroke.
PMID- 26437991
TI - Vessel Wall Imaging of the Intracranial and Cervical Carotid Arteries.
AB - Vessel wall imaging can depict the morphologies of atherosclerotic plaques,
arterial walls, and surrounding structures in the intracranial and cervical
carotid arteries beyond the simple luminal changes that can be observed with
traditional luminal evaluation. Differentiating vulnerable from stable plaques
and characterizing atherosclerotic plaques are vital parts of the early
diagnosis, prevention, and treatment of stroke and the neurological adverse
effects of atherosclerosis. Various techniques for vessel wall imaging have been
developed and introduced to differentiate and analyze atherosclerotic plaques in
the cervical carotid artery. High-resolution magnetic resonance imaging (HR-MRI)
is the most important and popular vessel wall imaging technique for directly
evaluating the vascular wall and intracranial artery disease. Intracranial artery
atherosclerosis, dissection, moyamoya disease, vasculitis, and reversible
cerebral vasoconstriction syndrome can also be diagnosed and differentiated by
using HR-MRI. Here, we review the radiologic features of intracranial artery
disease and cervical carotid artery atherosclerosis on HR-MRI and various other
vessel wall imaging techniques (e.g., ultrasound, computed tomography, magnetic
resonance, and positron emission tomography-computed tomography).
PMID- 26437993
TI - Endovascular Recanalization Therapy in Acute Ischemic Stroke: Updated Meta
analysis of Randomized Controlled Trials.
AB - BACKGROUND AND PURPOSE: Recent randomized clinical trials (RCTs) have
demonstrated benefits of endovascular recanalization therapy (ERT) contrary to
earlier trials. We aimed to estimate the benefits of ERT added to standard
therapy in acute ischemic stroke. METHODS: From a literature search of RCTs
testing ERT, we performed a meta-analysis to estimate an overall efficacy and
safety of ERT for all trials, stent-retriever trials, and RCTs comparing ERT and
intravenous tissue plasminogen activator (IV-TPA). RESULTS: We identified 15
relevant RCTs including 2,899 patients. For all trials, ERT was associated with
increased good outcomes (odds ratio [OR] 1.79; 95% confidence interval [CI] 1.34,
2.40; P<0.001) compared to the control. ERT also increased no or minimal
disability outcomes, good neurological recovery, good activity of daily living,
and recanalization. ERT did not significantly increase symptomatic intracranial
hemorrhage (SICH) (OR 1.19; 95% CI 0.83, 1.69; P=0.345) or death (OR 0.87; 95% CI
0.71, 1.05; P=0.151). In contrast, ERT significantly reduced extreme disability
or death (OR 0.77; 95% CI 0.61, 0.97; P=0.025). Restricting to five stent
retriever trials comparing ERT plus IV-TPA vs. IV-TPA alone, the benefit was even
greater for good outcome (OR 2.39; 95% CI 1.88, 3.04; P<0.001) and extreme
disability or death (OR 0.57; 95% CI 0.41, 0.78; P=0.001). Restricting to eight
RCTs comparing ERT (plus IV-TPA in six trials) with IV-TPA alone showed similar
efficacy and safety. CONCLUSIONS: This updated meta-analysis shows that ERT
substantially improves clinical outcomes and reduces extreme disability or death
without significantly increasing SICH compared to standard therapy.
PMID- 26437994
TI - Statins in Acute Ischemic Stroke: A Systematic Review.
AB - BACKGROUND AND PURPOSE: Statins have pleiotropic effects of potential
neuroprotection. However, because of lack of large randomized clinical trials,
current guidelines do not provide specific recommendations on statin initiation
in acute ischemic stroke (AIS). The current study aims to systematically review
the statin effect in AIS. METHODS: From literature review, we identified articles
exploring prestroke and immediate post-stroke statin effect on imaging surrogate
markers, initial stroke severity, functional outcome, and short-term mortality in
human AIS. We summarized descriptive overview. In addition, for subjects with
available data from publications, we conducted meta-analysis to provide pooled
estimates. RESULTS: In total, we identified 70 relevant articles including 6 meta
analyses. Surrogate imaging marker studies suggested that statin might enhance
collaterals and reperfusion. Our updated meta-analysis indicated that prestroke
statin use was associated with milder initial stroke severity (odds ratio [OR]
[95% confidence interval], 1.24 [1.05-1.48]; P=0.013), good functional outcome
(1.50 [1.29-1.75]; P<0.001), and lower mortality (0.42 [0.21-0.82]; P=0.0108). In
hospital statin use was associated with good functional outcome (1.31 [1.12
1.53]; P=0.001), and lower mortality (0.41 [0.29-0.58]; P<0.001). In contrast,
statin withdrawal was associated with poor functional outcome (1.83 [1.01-3.30];
P=0.045). In patients treated with thrombolysis, statin was associated with good
functional outcome (1.44 [1.10-1.89]; P=0.001), despite an increased risk of
symptomatic hemorrhagic transformation (1.63 [1.04-2.56]; P=0.035). CONCLUSIONS:
The current study findings support the use of statin in AIS. However, the
findings were mostly driven by observational studies at risk of bias, and thereby
large randomized clinical trials would provide confirmatory evidence.
PMID- 26437995
TI - Identifying Target Risk Factors Using Population Attributable Risks of Ischemic
Stroke by Age and Sex.
AB - BACKGROUND AND PURPOSE: Estimating age- and sex-specific population attributable
risks (PARs) of major risk factors for stroke may be a useful strategy to
identify risk factors for targeting preventive strategies. METHODS: For this case
control matched study, consecutive patients aged 18-90 years and admitted to nine
nationwide hospitals with acute ischemic stroke between December 2008 and June
2010, were enrolled as cases. Controls, individually matched by age and sex, were
chosen from the 4th Korean National Health & Nutrition Examination Survey (2008
2010). Based on odds ratios and prevalence, standardized according to the age and
sex structure of the Korean population, PARs of major risk factors were estimated
according to age (young, <= 45; middle-aged, 46-65; and elderly, >= 66 years) and
sex subgroups. RESULTS: In 4,743 matched case-control sets, smoking (PAR, 45.1%)
was the greatest contributing risk factor in young men, followed by hypertension
(28.5%). In middle-aged men, the greatest contributing factors were smoking
(37.4%), hypertension (22.7%), and diabetes (14.6%), whereas in women the
greatest factors were hypertension (22.7%) and stroke history (10.6%). In the
elderly, hypertension was the leading factor in men (23.7%) and women (23.4%).
Other noticeable factors were stroke history (men, 19.7%; women, 17.3%) and
diabetes (men, 12.5%; women, 15.1%). In young women, risk factors with a PAR
greater than 10% were not found. CONCLUSIONS: Smoking cessation in young people
and hypertension and diabetes control in older people may be effective in
reducing the burden of stroke on the population. In the elderly, secondary
prevention could also be emphasized.
PMID- 26437996
TI - Relation between Left Atrial Remodeling in Young Patients with Cryptogenic Stroke
and Normal Inter-atrial Anatomy.
AB - BACKGROUND AND PURPOSE: To investigate an association between left atrial (LA)
structural and P wave dispersion (PWD) during sinus rhythm, and electrical
remodeling in cryptogenic stroke (CS) patients. METHODS: Forty CS patients and 40
age- and sex-matched healthy controls were enrolled. P wave calculations were
based on 12-lead electrocardiography (ECG) at a 50-mm/s-paper speed with an
amplitude of 10 mm/mV. Difference between the maximum and minimum P wave duration
was the P wave dispersion (PWD=Pmax-Pmin). LA deformation was evaluated by
speckle tracking echocardiography within 3 days of the acute event. RESULTS: PWD
was 30.1+/-7.0 ms and 27.4+/-3.5 ms in CS and control group (P=0.02), whereas LA
maximum volume index [LAVImax] was 20.4+/-4.5 mL/m(2) and 19.9+/-2.4 mL/m(2) in
CS and control group, respectively (P = 0.04). While global peak LA strain was
[pLA-S] (LA reservoir function) 41.4 +/- 6.3% and 44.5 +/- 7.1% in CS and control
group, (P = 0.04), global peak late diastolic strain rate values [pLA-SRa] (LA
pump function) were 2.5 +/- 0.4% and 2.9 +/- 0.5% in CS and control group,
respectively (P = 0.001). A mild and a strong negative correlation between global
pLA-S and LAVImax (r=-0.49; P<0.01), and between PWD and global pLA-S (r = -0.52;
P < 0.01), respectively, was observed in CS. CONCLUSIONS: Increased PWD is
associated with impaired LA mechanical functions and enlargement, and involved in
the pathophysiology of AF or an AF-like physiology in CS.
PMID- 26437997
TI - Quantitative Magnetic Resonance Angiography in Internal Carotid Artery Occlusion
with Primary Collateral Pathway.
AB - BACKGROUND AND PURPOSE: Quantitative magnetic resonance angiography (Q-MRA)
enables direct measurement of volume flow rate (VFR) of intracranial arteries. We
aimed to evaluate the collateral flows in internal carotid artery (ICA) occlusion
with primary collateral pathway via circle of Willis using Q-MRA, and to compare
them between patients who recently developed ipsilateral symptomatic ischemia and
those who did not. METHODS: Between 2012 and 2014, 505 patients underwent Q-MRA
in our institution. Among these, 33 patients who had unilateral ICA occlusion
with primary collateral pathway were identified, and grouped into asymptomatic
patients, stable patients with chronic infarction, and symptomatic patients with
acute/subacute infarction. Mean VFR (mVFR) in intracranial arteries was measured
and compared between the patients' groups. Kruskal-Wallis test was used for
statistical analysis. RESULTS: Six patients were asymptomatic, fifteen with
chronic infarction were stable, and twelve with acute/subacute infarction were
symptomatic. The mVFR of ipsilateral middle cerebral artery in symptomatic
patients was significantly lower than those in stable or asymptomatic patients
(73.7+/-45.6 mL/min vs. 119.9+/-36.1 mL/min vs. 121.8+/-42.0 mL/min; P = 0.04).
Total sum of the mVFR of ipsilateral anterior, middle, and posterior cerebral
arteries was significantly lower in symptomatic patients than those in other
groups (229.3 +/- 51.3 mL/min vs. 282.0+/-68.6 mL/min vs. 314.0+/-44.4 mL/min; P
= 0.02). CONCLUSIONS: Q-MRA could be helpful to demonstrate the difference in the
degree of primary collateral flow in ICA occlusion between the patients with
recent symptomatic ischemia and those without.
PMID- 26437998
TI - Intravenous Tissue Plasminogen Activator Improves the Outcome in Very Elderly
Korean Patients with Acute Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: In a recent pooled analysis of randomized clinical trials
(RCTs), intravenous tissue plasminogen activator (TPA) improves the outcome in
patients aged >=80 years. However, it is uncertain whether the findings are
applicable to clinical practice in Asian populations. METHODS: From a multicenter
stroke registry database of Korea, we identified patients with acute ischemic
stroke who were aged >= 80 years. Using multivariable analysis and propensity
score (PS)-matched analyses, we assessed the effectiveness and safety of
intravenous TPA within 4.5 hours. RESULTS: Among 2,334 patients who met the
eligible criteria, 236 were treated with intravenous TPA (mean age, 83+/-5;
median NIHSS, 13 [IQR, 8-17]). At discharge, the TPA group compared to the no-TPA
group had a favorable shift on the modified Rankin Scale (mRS) score
(multivariable analysis, OR [95% CI], 1.51 [1.17-1.96], P=0.002; PS-matched
analysis, 1.54 [1.17-2.04], P=0.002) and was more likely to achieve mRS 0-1
outcome (multivariable analysis, 2.00 [1.32-3.03], P=0.001; PS-matched analysis,
1.59 [1.04-2.42], P=0.032). TPA treatment was associated with an increased risk
of symptomatic intracranial hemorrhage (multivariable analysis, 5.45 [2.80
10.59], P<0.001; PS-matched analysis, 4.52 [2.24-9.13], P<0.001), but did not
increase the in-hospital mortality (multivariable analysis, 0.86 [0.50-1.48],
P=0.58; PS-matched analysis, 0.88 [0.52-1.47], P=0.61). CONCLUSIONS: In the
setting of clinical practice, intravenous TPA within 4.5 hours improved the
functional outcome despite an increased risk of symptomatic intracranial
hemorrhage in very elderly Korean patients. The findings, consistent with those
from pooled analysis of RCTs, strongly support the use of TPA for this
population.
PMID- 26437999
TI - Endovascular Management of Long-Segmental Petrocavernous Internal Carotid Artery
(Carotid S) Occlusion.
AB - BACKGROUND AND PURPOSE: Long-segmental thrombotic occlusion of the distal
internal carotid artery (ICA) sparing the cervical segment proximally and the
supraclinoid segment distally, which could be termed 'Carotid S occlusion', has
an unusual clinical presentation. However, endovascular management of this lesion
is challenging. The purpose of our study is to report our endovascular treatment
clinical experience of the disease. METHODS: From March 2008 to June 2013, we
could identify 14 patients (average age: 62.1, median age: 62, range: 50-79) with
'Carotid S occlusion', who underwent endovascular recanalization procedures.
Patient's clinical presentations were collected and the imaging findings also
analyzed. The technical success rate, 24-hour and follow-up imaging outcome, and
the clinical outcome using the 90-day mRS (modified Rankin scale) score were
evaluated. RESULTS: Patients presented with gradually progressing (n = 8),
fluctuating (n = 3), transient ischemic attack (n = 2) and stationary (n = 1)
symptoms. DWI showed internal and external border-zone lesions in six patients,
only internal ICA border-zone lesions in three patients, and only external border
zone lesions in two patients. Underlying distal ICA stenosis was noted in 12
patients. The technical success rate was 92.8% (13/14). Luminal patency was noted
in all patients (100%) after 24 hours and in nine of 10 (90%) on long-term follow
up (median: 6.5, average: 15.1, range: 1-39 months). A 90-day, good functional
outcome (mRS <= 2) was noted in 13 of 14 patients (92.8%). CONCLUSIONS: 'Carotid
S occlusion' usually presented with border-zone infarction and endovascular
management of the lesions was feasible. A relatively successful clinical outcome
could be achieved after successful revascularization.
PMID- 26438002
TI - Carotid Stump as a Cause of Recurrent Embolism-Endovascular Treatment in a Case
of Congenital Carotid Stump Syndrome.
PMID- 26438000
TI - Anterior Optic Pathway Compression Due to Internal Carotid Artery Aneurysms:
Neurosurgical Management and Outcomes.
AB - BACKGROUND AND PURPOSE: Compression of the anterior optic pathway results in
visual deficits that can lead to the detection of unruptured aneurysms in the
internal carotid artery (ICA). The general types of treatment modalities for
aneurysms and visual deficits include surgery and endosaccular coiling. This
study retrospectively analyzed and compared the resolution of visual deficits
following surgery or endosaccular coiling. METHODS: We reviewed data on 33
patients with unruptured ICA aneurysms who presented with visual field deficits
caused by mass effects over the anterior optic pathway. Statistical analyses were
performed to identify the variables associated with the recovery of visual
symptoms. RESULTS: Eighteen patients underwent aneurysm clipping, 2 underwent
bypass surgery with endovascular trapping, and 2 underwent endovascular trapping
without bypass surgery (group A). Ten patients received endosaccular coiling
(group B). The visual outcomes included the following: in group A, 17 patients
(73.9%) demonstrated improvement and 6 patients (26.1%) demonstrated no changes
or worse outcomes; in group B, 2 patients (20.0%) demonstrated improvement and 8
patients (80.0%) demonstrated no changes or worse outcomes. Group A was
associated with a higher rate of favorable outcome than group B (P = 0.007).
According to the multivariate analysis, treatment without endosaccular coiling
(group A) was the only variable significantly associated with improvement of
visual outcome (P = 0.005; OR = 28.523; 95% CI = 2.683-303.171). CONCLUSIONS:
Treatment modality was the only predictor of improvement in visual deficits.
Treatment without endosaccular coiling resulted in visual improvement
significantly more often in comparison with endosaccular coiling.
PMID- 26438001
TI - The Effects of Transcranial Direct-Current Stimulation on Cognition in Stroke
Patients.
AB - BACKGROUND AND PURPOSE: To investigate whether transcranial direct-current
stimulation (tDCS) can improve cognition in stroke patients. METHODS: Forty-five
stroke patients (20 males and 25 females, average age: 62.7 years) with cognitive
dysfunction were included in this prospective, double-blinded, randomized case
control study. All patients were right-handed and the mean elapsed time after
stroke was 39.3 days. Three different treatments groups were used: (1) anodal
stimulation of the left anterior temporal lobe, (2) anodal stimulation of the
right anterior temporal lobe, and (3) sham stimulation. tDCS was delivered for 30
minutes at 2 mA with 25 cm(2) electrodes, five times/week, for a total of 3
weeks, using a Phoresor II Auto Model PM 850 (IOMED((r))). The evaluation of
cognitive impairment was based on a Computerized Neuropsychological Test (CNT),
Korean Mini-Mental State Examination (K-MMSE). The Korean version of the Modified
Barthel Index (K-MBI) was used to assess activities of daily living
functionality. These evaluations were conducted in all patients before and after
treatment. RESULTS: Each group included 15 patients. Pre-treatment evaluation
showed no significant differences between the three groups for any of the
parameters. There was significant improvement in the verbal learning test on the
CNT in the left anodal stimulation group (P < 0.05). There were, however, no
significant differences in the K-MMSE or K-MBI scores among the three groups.
CONCLUSIONS: These results demonstrated the beneficial effects of anodal tDCS on
memory function. Thus, tDCS can successfully be used as a treatment modality for
patients with cognitive dysfunction after stroke.
PMID- 26438003
TI - Malignant Cerebral Venous Sinus Thrombosis in Polycythemia.
PMID- 26438004
TI - Dabigatran Effect on Left Ventricular Thrombus in a Patient with Acute Ischemic
Stroke.
PMID- 26438005
TI - Updated Korean Clinical Practice Guidelines on Decompressive Surgery for
Malignant Middle Cerebral Artery Territory Infarction.
PMID- 26438006
TI - ERRATUM: Table Correction: Case Characteristics, Hyperacute Treatment, and
Outcome Information from the Clinical Research Center for Stroke-Fifth Division
Registry in South Korea.
PMID- 26438007
TI - ERRATUM: Author's Name Correction: Evolution of Endovascular Therapy in Acute
Stroke: Implications of Device Development.
PMID- 26438008
TI - Biliary strictures and recurrence after liver transplantation for primary
sclerosing cholangitis: A retrospective multicenter analysis.
AB - Liver transplantation (LT) is the only definitive treatment for patients with end
stage liver disease due to primary sclerosing cholangitis (PSC), but a high rate
of biliary strictures (BSs) and of recurrent primary sclerosing cholangitis
(recPSC) has been reported. In this multicenter study, we analyzed a large
patient cohort with a long follow-up in order to evaluate the incidence of BS and
recPSC, to assess the impact on survival after LT, and to identify risk factors.
We collected clinical, surgical, and laboratory data and records on inflammatory
bowel disease (IBD), immunosuppression, recipient and graft outcome, and biliary
complications (based on cholangiography and histology) of all patients who
underwent LT for PSC in 10 German transplant centers between January 1990 and
December 2006; 335 patients (68.4% men; mean age, 38.9 years; 73.5% with IBD)
underwent transplantation 8.8 years after PSC diagnosis with follow-up for 98.8
months. The 1-, 5-, and 10-year recipient and graft survival was 90.7%, 84.8%,
79.4% and 79.1%, 69.0%, 62.4%, respectively. BS was diagnosed in 36.1% after a
mean time of 3.9 years, and recPSC was diagnosed in 20.3% after 4.6 years. Both
entities had a significant impact on longterm graft and recipient survival.
Independent risk factors for BS were donor age, ulcerative colitis, chronic
ductopenic rejection, bilirubin, and international normalized ratio (INR) at LT.
Independent risk factors for recPSC were donor age, IBD, and INR at LT. These
variables were able to categorize patients into risk groups for BS and recPSC. In
conclusion, BS and recPSC affect longterm graft and patient survival after LT for
PSC. Donor age, IBD, and INR at LT are independent risk factors for BS and recPSC
and allow for risk estimation depending on the recipient-donor constellation.
PMID- 26438009
TI - Streptobacillus notomytis sp. nov., isolated from a spinifex hopping mouse
(Notomys alexis Thomas, 1922), and emended description of Streptobacillus
Levaditi et al. 1925, Eisenberg et al. 2015 emend.
AB - A pleomorphic, Gram-negative, rod-shaped, indole-, oxidase- and catalase
negative, non-spore-forming, non-motile bacterium was isolated in 1979 from the
heart of a spinifex hopping mouse (Notomys alexis Thomas, 1922) with septicaemia
and stored as Streptobacillus moniliformis in the strain collection of the Animal
Health Laboratory, South Perth, Western Australia (AHL 370-1), as well as under
CCUG 12425. On the basis of 16SrRNA gene sequence analyses, the strain was
assigned to the genus Streptobacillus, with 99.4 % sequence similarity to the
type strain of Streptobacillus moniliformis, 95.6 %sequence similarity to the
type strain of Streptobacillus hongkongensis and 99.0 %sequence similarity to the
type strain of Streptobacillus felis. The clear differentiation of strain AHL 370
1T from Streptobacillus moniliformis, Streptobacillus hongkongensis and
Streptobacillus felis was also supported by rpoB, groEL and recA nucleotide and
amino acid sequence analysis. Average nucleotide identity was 87.16 % between
strain AHL 370-1T and Streptobacillus moniliformis DSM 12112T. Physiological data
confirmed the allocation of strain AHL 370-1T to the family Leptotrichiaceae,
considering the very similar profiles of enzyme activities and fatty acids
compared to closely related species. Within the genus Streptobacillus,isolate AHL
370-1T could also be separated unambiguously from the type strains of
Streptobacillus moniliformis, Streptobacillus hongkongensis and Streptobacillus
felis by MALDI-TOF mass spectrometry. Two further strains (KWG2 and KWG24)
isolated from asymptomatic black rats in Japan were highly similar to AHL 370-1T.
On the basis of these data, we propose the novel species Streptobacillus
notomytis sp. nov., with the type strain AHL370-1T (=CCUG 12425T=DSM 100026T=CCM
8593T=EF 12425T).
PMID- 26438010
TI - The intraindividual impact of ADHD on the transition of adulthood to old age.
AB - The aim of the study was to explore whether the individual burden of ADHD is the
same in the elderly as in younger ages even though the symptomatological impact
of ADHD seems to remain stable over the lifespan. To assess ADHD symptoms and
ADHD-associated problems in daily life, standardised questionnaires were
conducted. To assess the subjectively experienced course of disease over the
lifespan, all participants were interviewed regarding symptoms of ADHD in
childhood as well as before and after the fiftieth year of life. In the sample of
296 respondents with a mean age of 69.55 years, 11 fulfilled the criteria of
adult ADHD. Retrospectively, the ADHD subjects reported negative impacts due to
ADHD-associated behaviour over the life span. These impairments remained stable
over time with 18 % of subjects reporting impairments in family life, 46 % in
social relationships, 18 % in dealing with money, and 36 % in organisation of
daily life in the presence. Thus, the ADHD subjects reported problems with
stability over time caused by low self-confidence, being quick-tempered, and due
to defiantness. Although this is pilot study, our results reflect the burden of
ADHD not only in young and middle adulthood, but also in seniority. The findings
indicate the lifelong impact of ADHD as the explored seniors with ADHD reported
the negative impact of ADHD remaining stable over the lifespan.
PMID- 26438011
TI - Deeply divergent sympatric mitochondrial lineages of the earthworm Lumbricus
rubellus are not reproductively isolated.
AB - BACKGROUND: The accurate delimitation of species is essential to numerous areas
of biological research. An unbiased assessment of the diversity, including the
cryptic diversity, is of particular importance for the below ground fauna, a
major component of global biodiversity. On the British Isles, the epigeic
earthworm Lumbricus rubellus, which is a sentinel species in soil ecotoxicology,
consists of two cryptic taxa that are differentiated in both the nuclear and the
mitochondrial (mtDNA) genomes. Recently, several deeply divergent mtDNA lineages
were detected in mainland Europe, but whether these earthworms also constitute
cryptic species remains unclear. This information is important from an
evolutionary perspective, but it is also essential for the interpretation and the
design of ecotoxicological projects. In this study, we used genome-wide RADseq
data to assess the reproductive isolation of the divergent mitochondrial lineages
of L. rubellus that occur in sympatry in multiple localities in Central Europe.
RESULTS: We identified five divergent (up to 16 % net p-distance) mitochondrial
lineages of L. rubellus in sympatry. Because the clustering of the RADseq data
was according to the population of origin and not the mtDNA lineage, reproductive
isolation among the mtDNA lineages was not likely. Although each population
contained multiple mtDNA lineages, subdivisions within the populations were not
observed for the nuclear genome. The lack of fixed differences and sharing of the
overwhelming majority of nuclear polymorphisms between localities, indicated that
the populations did not constitute allopatric species. The nucleotide diversity
within the populations was high, 0.7-0.8 %. CONCLUSIONS: The deeply divergent
mtDNA sympatric lineages of L. rubellus in Central Europe were not reproductively
isolated groups. The earthworm L. rubellus, which is represented by several mtDNA
lineages in continental Europe, apparently is a single highly polymorphic species
rather than a complex of several cryptic species. This study demonstrated the
critical importance of the use of multilocus nuclear data for the unbiased
assessment of cryptic diversity and for the delimitation of species in soil
invertebrates.
PMID- 26438012
TI - Dehydroepiandrosterone sulphate: diabolical hormone or epiphenomenon in
aneurysmal subarachnoid hemorrhage?
AB - Inflammation is purported to play an important role in the clinical course of
subarachnoid hemorrhage. The current study by Hollig et al. entails using
dehydroepiandrosterone sulfate, a hormone that inhibits key inflammatory
pathways, as a predictor of functional outcome in these patients.
PMID- 26438013
TI - A cross-sectional investigation of parenting style and friendship as mediators of
the relation between social class and mental health in a university community.
AB - INTRODUCTION: This study tested a novel explanation for the positive relation
between social class and mental health among university students. Students with a
higher social class were expected to have experienced more authoritative and less
authoritarian parenting styles; these parenting styles were expected to lead to
greater friendship and social integration at university; and greater friendship
and integration were expected to lead to better mental health. METHOD: To test
this model, the researchers asked 397 Australian undergraduate students to
complete an online survey. The research used a cross-sectional correlational
design, and the data was analysed using bootstrapped multiple serial mediation
tests. RESULTS: Consistent with predictions, parenting style, general friendship
and support, and social integration at university mediated the relation between
social class and mental health. CONCLUSIONS: The present results suggest that
working-class parenting styles may inhibit the development of socially-supportive
friendships that protect against mental health problems. The potential
effectiveness of interventions based on (a) social integration and (b) parenting
style is discussed. Future research in this area should employ a longitudinal
research design in order to arrive at clearer causal conclusions about the
relations between social class, parenting styles, friendship, social integration,
and mental health.
PMID- 26438014
TI - Meta-analysis comparing doublet and single cytotoxic agent therapy as first-line
treatment in elderly patients with advanced nonsmall-cell lung cancer.
AB - OBJECTIVE: To perform a systematic review and meta-analysis comparing doublet
versus single agent therapy in elderly patients with advanced nonsmall-cell lung
cancer (NSCLC). METHODS: PubMed(r) and Cochrane databases, and American Society
of Clinical Oncology, World Congress of Lung Cancer, and European Society of
Medical Oncology abstracts were searched. Endpoints were overall survival (OS), 1
year survival rate (1-year SR), overall response rate (ORR), and grade 3/4
adverse events. Subgroup analyses were based on chemotherapy regimens and race.
RESULTS: Out of 11 studies (13 randomized trials; n = 2782), doublet therapy was
associated with significantly increased OS (hazard ratio [HR] 0.89, 95%
confidence interval [CI] 0.83, 0.95), 1-year SR (risk ratio [RR] 1.15, 95% CI
1.04, 1.28), and ORR (RR 1.39, 95% CI 1.39, 1.86) versus single-agents.
Chemotherapy regimen-based subgroup analyses favoured platinum-based doublet
therapy for OS (RR 0.71, 95% CI 0.60, 0.84), 1-year SR (RR 1.28, 95% CI 1.11,
1.47), and ORR (RR 1.88, 95% CI 1.49, 2.38). Race-based subgroup analyses
revealed increased benefit from doublet therapy in Asian populations for ORR (RR
1.70, 95% CI 1.29, 2.23) but not increased survival benefit. Higher incidences of
grade 3/4 anaemia (RR 2.23, 95% CI 1.61, 3.09), thrombocytopenia (RR 2.47, 95% CI
1.17, 5.20), and fatigue (RR 1.36, 95% CI 1.06, 1.74) were observed with doublet
versus single-agent therapy. CONCLUSIONS: Doublet therapy was associated with
significantly increased OS, 1-year SR and ORR compared with single agent therapy.
Race may be considered when choosing doublet versus single-agent therapy as first
line treatment of NSCLC in elderly patients.
PMID- 26438015
TI - Arthroplasty and postoperative antimicrobial prophylaxis.
PMID- 26438016
TI - UN goals trigger calls for reforming Canadian aid.
PMID- 26438017
TI - Bones of contention.
PMID- 26438018
TI - Artificial scents have no place in our hospitals.
PMID- 26438019
TI - A 29-year-old woman with Crohn disease considering pregnancy.
PMID- 26438020
TI - Nunavut suicides a "public health emergency".
PMID- 26438021
TI - Expect little, demand more from feds on health.
PMID- 26438022
TI - Election 2015: closing the Aboriginal health gap.
PMID- 26438023
TI - Maternal and child health: gains, but a long journey ahead.
PMID- 26438024
TI - Medicine by design.
PMID- 26438025
TI - Tools for translational epigenetic studies involving formalin-fixed paraffin
embedded human tissue: applying the Infinium HumanMethyation450 Beadchip assay to
large population-based studies.
AB - BACKGROUND: Large population-based translational epigenetic studies are emerging
due to recent technological advances that have made molecular analyses possible.
For example, the Infinium HumanMethylation450 Beadchip (HM450K) has enabled
studies of genome-wide methylation on a scale not previously possible. However,
application of the HM450K to DNA extracted from formalin-fixed paraffin-embedded
(FFPE) tumour material has been more challenging than application to high quality
DNA extracted from blood. To facilitate the application of this assay
consistently across a large number of FFPE tumour-enriched DNA samples we have
devised a modification to the HM450K protocol for FFPE that includes an
additional quality control (QC) checkpoint. RESULTS: QC checkpoint 3 was designed
to assess the presence of DNA after bisulfite conversion and restoration, just
prior to application of the HM450K assay. DNA was extracted from 474 archival
FFPE breast tumour material. Five samples did not have a detectable amount of DNA
with an additional 42 failing to progress past QC checkpoint 3. Genome-wide
methylation was measured for the remaining 428 tumour-enriched DNA. Of these,
only 4 samples failed our stringent HM450K data criteria thus representing a 99%
success rate. Using prior knowledge about methylation marks associated with
breast cancer we further explored the quality of the data. Twenty probes in the
BRCA1 promoter region showed increased methylation in triple-negative breast
cancers compared to Luminal A, Luminal B and HER2-positive breast cancer
subtypes. Validation of this observation in published data from The Cancer Genome
Atlas (TCGA) Network (obtained from DNA extracted from fresh frozen tumour
samples) confirms the quality of the data obtained from the improved protocol.
CONCLUSIONS: The modified protocol is suitable for the analysis of FFPE tumour
enriched DNA and can be systematically applied to hundreds of samples. This
protocol will have utility in population-based translational epigenetic studies
and is applicable to a wide variety of translated studies interested in analysis
of methylation and its role in the predisposition to disease and disease
progression.
PMID- 26438026
TI - Human Anthrax Transmission at the Urban-Rural Interface, Georgia.
AB - Human anthrax has increased dramatically in Georgia and was recently linked to
the sale of meat in an urban market. We assessed epidemiological trends and risk
factors for human anthrax at the urban-rural interface. We reviewed epidemiologic
records (2000-2012) that included the place of residence (classified as urban,
peri-urban, or rural), age, gender, and self-reported source of infection
(handling or processing animal by-products and slaughtering or butchering
livestock). To estimate risk, we used a negative binomial regression. The average
incidence per 1 million population in peri-urban areas (24.5 cases) was > 2-fold
higher compared with rural areas and > 3-fold higher compared with urban area.
Risk from handling or purchasing meat was nearly 2-fold higher in urban areas and
> 4-fold higher in peri-urban areas compared with rural area. Our findings
suggest a high risk of anthrax in urban and peri-urban areas likely as a result
of spillover from contaminated meat and animal by-products. Consumers should be
warned to purchase meat only from licensed merchants.
PMID- 26438027
TI - Hepatitis E Virus Exposure is Increased in Pork Butchers from Burkina Faso.
AB - We conducted the first survey of zoonotic risk of Hepatitis E virus (HEV)
transmissions in Ouagadougou, Burkina Faso, through the direct contact with pork
meat during professional activity. Anti-HEV antibodies were more prevalent in
pork butchers, 76% than in the general population, which was 47.8% in 2013 (odds
ratio = 3.46, 95% CI = 2.85-4.21, P < 0.001). Among slaughter-aged swine, HEV
seroprevalence was of 80%, and HEV RNA was detected in 1% of pork livers.
Phylogenetic analysis pointed out HEV genotype 3. Thus, in addition to possible
HEV contamination through the water source, as in endemic region, zoonotic
transmissions of HEV probably occur in west Africa.
PMID- 26438028
TI - Does Poor Water Quality Cause Diarrheal Disease?
PMID- 26438029
TI - Knowledge, Attitudes, and Practices Associated with Brucellosis in Livestock
Owners in Jordan.
AB - We evaluated livestock owners' knowledge, attitudes, and practices regarding
brucellosis in Jordan. A questionnaire was administered and biological samples
were examined to verify the serological status of animals. Seroprevalence
estimates indicated that 18.1% (95% CI: 11-25.3) of cattle herds and 34.3% (95%
CI: 28.4-40.4) of small ruminant flocks were seropositive. The results showed
that 100% of the interviewed livestock keepers were aware of brucellosis: 87%
indicated a high risk of infection if unpasteurized milk is consumed and 75%
indicated a high risk if unpasteurized dairy products are consumed. Awareness of
the risk of infection through direct contact with fetal membranes or via physical
contact with infected livestock is considerably lower, 19% and 13%, respectively.
These knowledge gaps manifest in a high frequency of high-risk practices such as
assisting in animal parturition (62%), disposing aborted fetuses without
protective gloves (71.2%) or masks (65%), and not boiling milk before preparation
of dairy products (60%). When brucellosis is suspected, basic hygiene practices
are often disregarded and suspect animals are freely traded. Public health
education should be enhanced as the disease is likely to remain endemic in the
ruminant reservoir as long as a suitable compensation program is not established
and trust on available vaccines is regained.
PMID- 26438030
TI - A Cost-Effectiveness Analysis of Plasmodium falciparum Malaria Elimination in
Hainan Province, 2002-2012.
AB - In Hainan Province, China, great achievements in elimination of falciparum
malaria have been made since 2010. There have been no locally acquired falciparum
malaria cases since that time. The cost-effectiveness of elimination of
falciparum malaria has been analyzed in Hainan Province. There were 4,422
falciparum malaria cases reported from 2002 to 2012, more cases occurred in males
than in females. From 2002 to 2012, a total of 98.5 disability-adjusted life
years (DALYs) were reported because of falciparum malaria. Populations in the age
ranges of 15-25 and 30-44 years had higher incidences and DALYs than other age
groups. From 2002 to 2012, malaria-related costs for salaries of staff, funds
from the provincial government, national government, and the GFATM were US$3.02,
US$2.24, US$1.44, and US$5.08 million, respectively. An estimated 9,504
falciparum malaria cases were averted during the period 2003-2012. The estimated
cost per falciparum malaria case averted was US$116.5. The falciparum malaria
elimination program in Hainan was highly effective and successful. However,
funding for maintenance is still needed because of imported cases.
PMID- 26438031
TI - Microbiological Contamination of Drinking Water Associated with Subsequent Child
Diarrhea.
AB - We used a prospective, longitudinal cohort enrolled as part of a program
evaluation to assess the relationship between drinking water microbiological
quality and child diarrhea. We included 50 villages across rural Bangladesh.
Within each village field-workers enrolled a systematic random sample of 10
households with a child under the age of 3 years. Community monitors visited
households monthly and recorded whether children under the age of 5 years had
diarrhea in the preceding 2 days. Every 3 months, a research assistant visited
the household and requested a water sample from the source or container used to
provide drinking water to the child. Laboratory technicians measured the
concentration of Escherichia coli in the water samples using membrane filtration.
Of drinking water samples, 59% (2,273/3,833) were contaminated with E. coli. Of
12,192 monthly follow-up visits over 2 years, mothers reported that their child
had diarrhea in the preceding 2 days in 1,156 (9.5%) visits. In a multivariable
general linear model, the log10 of E. coli contamination of the preceding
drinking water sample was associated with an increased prevalence of child
diarrhea (prevalence ratio = 1.14, 95% CI = 1.05, 1.23). These data provide
further evidence of the health benefits of improved microbiological quality of
drinking water.
PMID- 26438032
TI - Hospital-Based Surveillance for Infectious Etiologies Among Patients with Acute
Febrile Illness in Georgia, 2008-2011.
AB - Information on the infectious causes of undifferentiated acute febrile illness
(AFI) in Georgia is essential for effective treatment and prevention. In May
2008, a hospital-based AFI surveillance was initiated at six hospitals in
Georgia. Patients aged >= 4 years with fever >= 38 degrees C for >= 48 hours were
eligible for surveillance. Blood culture and serologic testing were conducted for
Leptospira spp., Brucella spp., West Nile virus (WNV), Crimean-Congo hemorrhagic
fever virus, Coxiella burnetii, tick-borne encephalitis virus (TBEV), hantavirus,
Salmonella enterica serovar Typhi (S. Typhi), and Rickettsia typhi. Of 537
subjects enrolled, 70% were outpatients, 54% were males, and the mean age was 37
years. Patients reported having fatigue (89%), rigors (87%), sweating (83%), pain
in joints (49%), and sleep disturbances (42%). Thirty-nine (7%) patients were
seropositive for R. typhi, 37 (7%) for Brucella spp., 36 (7%) for TBEV, 12 (2%)
for Leptospira spp., 10 (2%) for C. burnetii, and three (0.6%) for S. Typhi. None
of the febrile patients tested positive for WNV antibodies. Of the patients, 73%
were negative for all pathogens. Our results indicate that most of the targeted
pathogens are present in Georgia, and highlight the importance of enhancing
laboratory capacity for these infectious diseases.
PMID- 26438034
TI - Effect of interfaces on the nearby Brownian motion.
AB - Near-boundary Brownian motion is a classic hydrodynamic problem of great
importance in a variety of fields, from biophysics to micro-/nanofluidics.
However, owing to challenges in experimental measurements of near-boundary
dynamics, the effect of interfaces on Brownian motion has remained elusive. Here
we report a computational study of this effect using MUs-long large-scale
molecular dynamics simulations and our newly developed Green-Kubo relation for
friction at the liquid-solid interface. Our computer experiment unambiguously
reveals that the t(-3/2) long-time decay of the velocity autocorrelation function
of a Brownian particle in bulk liquid is replaced by a t(-5/2) decay near a
boundary. We discover a general breakdown of traditional no-slip boundary
condition at short time scales and we show that this breakdown has a profound
impact on the near-boundary Brownian motion. Our results demonstrate the
potential of Brownian-particle-based micro-/nanosonar to probe the local
wettability of liquid-solid interfaces.
PMID- 26438033
TI - Relationship between ITPA polymorphisms and hemolytic anemia in HCV-infected
patients after ribavirin-based therapy: a meta-analysis.
AB - BACKGROUND: There is growing evidence that variations in the gene encoding
inosine triphosphate pyrophosphohydrolase (ITPase), known as inosine
triphosphatase (ITPA), are related to hemolytic anemia, which is frequently
observed among hepatitis C virus (HCV)-infected patients receiving ribavirin
(RBV)-based therapy. We performed a meta-analysis of all eligible studies
assessing ITPA gene polymorphisms related to RBV-induced hemolytic anemia in HCV
infected patients published in PubMed, Embase and the Cochrane library prior to
the end of 2014. METHODS: Three outcomes were evaluated: (1) hemoglobin decline,
(2) severe anemia, and (3) RBV dose reduction or treatment discontinuation.
Pooled odds ratio (OR) and 95 % confidence interval (95 % CI) were estimated by
either fixed or random effects models. RESULTS: Twenty-nine studies were selected
from the literature search: 20 references involving 6533 individuals for
hemoglobin decline, 13 references on 3764 patients for severe anemia, and 16
references on 3918 patients for RBV dose reduction or discontinuation.
Significant associations with hemoglobin decline were found for rs1127354 CC [OR
= 12.84 (95 % CI 7.44; 22.17)], rs7270101 AA [OR = 3.41 (95 % CI 2.08; 5.59)] and
rs6051702 AA [OR = 4.43 (95 % CI 2.80; 7.00)] genotypes. Moreover, significant
associations with hemoglobin decline were also found for absent [OR = 6.01 (95 %
CI 4.84; 7.46)] and mild [OR = 4.68 (95 % CI 2.83; 7.74)] ITPase deficiency
haplotypes. The ITPA rs1127354 CC genotype and absent ITPase deficiency haplotype
were also associated with severe anemia {[OR = 7.77 (95 % CI 5.03; 12.00)] and
[OR = 4.79 (95 % CI 1.69; 13.56)], respectively}. Additionally, the rs1127354 CC
genotype showed significant association with RBV dose reduction or stopping
treatment (OR = 2.24; 95 % CI 1.79; 2.81). CONCLUSIONS: ITPA polymorphisms
increase the likelihood of developing hemolytic anemia for HCV-infected patients
on RBV-based therapy, particularly rs1127354 CC and rs7270101 AA genotypes,
suggesting the utility of screening for ITPA polymorphisms to avoid hematological
toxicity and increase adherence to RBV-based therapy.
PMID- 26438035
TI - Extracts from Aralia elata (Miq) Seem alleviate hepatosteatosis via improving
hepatic insulin sensitivity.
AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease
that is strongly associated with obesity and dysregulation of insulin in the
liver. However, currently no pharmacological agents have been established for the
treatment of NAFLD. In this regard, we sought to evaluate the anti-NAFLD effects
of Aralia elata (Miq) Seem (AE) extract and its ability to inhibit hepatic lipid
accumulation and modulate cellular signaling in a high fat diet (HFD)-induced
obese mouse model. METHODS: A model of hepatic steatosis in the HepG2 cells was
induced by oleic acid. Intracellular lipid droplets were detected by Oil-Red-O
staining, and the expression of sterol regulatory element-binding protein 1(SREBP
1), Fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC) 1 and 2, Peroxisome
proliferator activated receptor-alpha (PPARalpha), and carnitine palmitoyl
transferase 1(CPT-1) was analyzed by real time reverse transcription-Polymerase
chain reaction (qRT-PCR). And glucose consumption was measured with commercial
kit. Furthermore, Male C57BL/6 J mice were fed with HFD to induce NAFLD. Groups
of mice were given plant extracts orally at 100 and 300 mg/kg at daily for 4
weeks. After 3 weeks of AE extract treatment, we performed oral glucose tolerance
test (OGTT). Liver tissue was procured for histological examination,
Phosphoinositide 3-kinase (PI3K) and Protein kinase B (PKB/Akt) activity.
RESULTS: In the present study, AE extract was shown to reduce hepatic lipid
accumulation and significantly downregulate the level of lipogenic genes and
upregulate the expression of lipolysis genes in HepG2 cells. And also, AE extract
significantly increased the glucose consumption, indicating that AE extract
improved insulin resistance. Subsequently, we confirmed the inhibitory activity
of AE extract on NAFLD, in vivo. Treatment with AE extract significantly
decreased body weight and the fasting glucose level, alleviated hyperinsulinism
and hyperlipidemia, and reduced glucose levels, as determined by OGTT.
Additionally, AE extract decreased PI3K and Akt activity. CONCLUSIONS: Our
results suggest that treatment with AE extract ameliorated NAFLD by inhibiting
insulin resistance through activation of the Akt/GLUT4 pathway.
PMID- 26438037
TI - Intersubjectivity, otherness, and thirdness: A necessary relationship.
AB - The author proposes an interplay among the notions of otherness,
intersubjectivity and thirdness with its coincidences and oppositions. Its
polysemic nature is analyzed in this paper. The relation internal world-external
world is at stake and concerns both the construction of subjectivity as well as
the way the analytic relation is deemed to assume. This review focuses on the
psychoanalytic developments from Freud to posfreudian and contemporary authors
plus, at the same time, interdisciplinary proposals are also included. It is also
revisited the notion of "analytic field", proposed by Willy and Madeleine
Baranger who, early as 1961-62, underlined the transition from "the unipersonal
to the intersubjective", emphasizing that this was an expression of a change in
the understanding of the analytic treatment. In this paper, the author argues
that the concept of otherness introduces a symbolic aspect of decentring into the
seeming interactive symmetry of intersubjectivity. At the same time, it is
stressed that thirdness places a wedge into the between-subjects, which opens the
way from and to recognition of the other and others.
PMID- 26438036
TI - Maternal and Child's Thyroid Function and Child's Intellect and Scholastic
Performance.
AB - BACKGROUND: Maternal hypothyroidism and/or hypothyroxinemia have been associated
with child's poor neuropsychological development, but the results have been
inconsistent. METHODS: The Northern Finland Birth Cohort 1986 included all
expected births within a year (9362 women, 9479 children) from the two
northernmost provinces of Finland. Maternal serum samples (n = 5791) were
obtained in early pregnancy (M +/- SD = 10.7 +/- 2.8 weeks' gestation), and serum
samples from their children were obtained at 16 years of age (n = 5829). All
samples were analyzed for thyrotropin, free thyroxine (fT4), and thyroid
peroxidase antibodies. The children's school performance was evaluated by their
main teachers at eight years of age, as well as by the adolescents themselves at
16 years of age. Data on possible severe intellectual deficiency and mild
cognitive limitation were collected from healthcare records and registries for
all children. Logistic regression estimated the odds of poor school performance
or severe intellectual deficiency/mild cognitive limitation associated with
exposure to maternal thyroid dysfunction. The odds of poor school performance
associated with the adolescents' own thyroid function at age 16 were also
estimated. Results are presented as odds ratios (OR) with confidence intervals
(CI), adjusted for maternal/family covariates and child's sex. RESULTS: Girls of
mothers with subclinical hypothyroidism had more self-evaluated difficulties in
mathematics than did girls of euthyroid mothers (OR 1.62 [CI 1.06-2.49]). Boys of
hypothyroxinemic mothers repeated a school class more often than did boys of
euthyroid mothers (OR 5.46 [CI 1.19-25.06]). Adolescents of hyperthyroid mothers
had increased odds of poor self-evaluated performance in mathematics (OR 1.61 [CI
1.01-2.49]). Maternal thyroid dysfunction did not increase the odds of a child
having severe intellectual deficiency/mild cognitive limitation. At 16 years of
age, girls with hyperthyroidism by laboratory measurements had more difficulties
in Finnish language (OR 2.82 [CI 1.42-5.61]) than did euthyroid girls. Boys with
hypothyroxinemia by laboratory measurement had higher odds of having difficulties
in Finnish and/or mathematics (OR 2.13 [CI 1.26-3.62]) than did euthyroid boys.
CONCLUSIONS: Maternal thyroid dysfunction during early pregnancy was associated
with poorer scholastic performance of the adolescent. Additionally, adolescents'
own thyroid dysfunction was associated with difficulties in school performance
assessed by self-evaluation.
PMID- 26438038
TI - Efficacy and safety of iota-carrageenan nasal spray versus placebo in early
treatment of the common cold in adults: the ICICC trial.
AB - Iota-carrageenan (I-C) is active against respiratory viruses in vitro and was
effective as nasal spray in three previous clinical trials. The current trial
served to further investigate I-C in patients with early common cold symptoms.
METHODS: This randomized, placebo-controlled, double-blind phase IV trial was
conducted in 200 adult patients with self-diagnosed colds of <48 h' duration that
were confirmed by baseline cold symptom scores. Patients were to self-administer
0.12 % I-C or placebo spray (NaCl 0.5 %) four times daily for four to ten days
and record symptom information for ten days. Common respiratory viruses were
quantified by RT-PCR during pretreatment and on Day 3 or 4. The primary endpoint
was the mean total symptom score (TSS) of eight cold symptoms on Days 2-4 (TSS2
4). RESULTS: Patients in both treatment groups had similar baseline TSSs (mean
TSS: 6.75 for I-C and 6.79 for placebo). Viruses were detected in baseline
samples from 53 of 98 I-C patients (54.1 %) and 54 of 97 placebo patients (55.7
%). Mean +/- SE for TSS2-4 was 5.78 +/- 0.25 for I-C patients and 6.39 +/- 0.25
for placebo (p = 0.0895). Exploratory analyses after unblinding (TSS2-4 excluding
a patient with aberrantly high symptom scores [TSS2-4, ex 1pt]; mean of TSS over
Days 1-4 [TSS1-4]; change in TSS1-4 relative to baseline [TSS1-4, rel])
demonstrated treatment differences in favor of I-C (p = 0.0364, p = 0.0495 and p
= 0.0421, respectively). For patients with quantifiable rhinovirus/enterovirus at
baseline, there was a trend towards greater reduction of virus load at Day 3 or 4
(p = 0.0958; I-C: 90.2 % reduction in viral load; placebo: 72.0 %). Treatments
were well tolerated with no differences in adverse event rates. CONCLUSIONS: The
primary endpoint did not demonstrate a statistically significant difference
between I-C and placebo but showed a trend towards I-C benefit. Exploratory
analyses indicated significant reduction of cold symptoms in the I-C group
relative to placebo during the first four days when symptoms were most severe,
and also substantiated I-C's activity against rhinovirus/enterovirus. TRIAL
REGISTRATION: NCT01944631 (clinicaltrials.gov).
PMID- 26438039
TI - Long-term hemodialysis therapy in neonates and infants with end-stage renal
disease: a 16-year experience and outcome.
AB - BACKGROUND: Peritoneal dialysis is the preferred mode of renal replacement
therapy in infants with end-stage renal disease (ESRD). Hemodialysis (HD) is
seldom used in neonates and infants due to the risk of major complications in the
very young. METHODS: Demographic, clinical, laboratory, and imaging data on all
infants younger than 12 months with ESRD who received HD in our Pediatric
Dialysis Unit between January 1997 and June 2013 were analyzed. RESULTS: Eighteen
infants (n = 6 male) with ESRD (median age 3 months; median weight 4.06 kg)
received HD through a central venous catheter (CVC) for a total of 543 months
(median duration per infant 16 months). Seven of the infants (39%) were neonates,
and five (28%) had serious comorbidities. There were five episodes of CVC
infection, which is a rate of 0.3/1000 CVC days. Median catheter survival time
was 320 days. Most infants had good oral intake, and only four (22%) required a
gastric tube; 14 (78%) infants displayed normal growth. Fourteen (78%) infants
had hypertension, of whom four (22%) had severe cardiac complications; eight
(44%) showed delayed psychomotor development. Eleven (61%) of the infants,
including six (86%) of the neonates, survived. Five (28%) infants underwent renal
transplantation; 10-year graft survival was 80%. CONCLUSIONS: Based on these
results, long-term HD in neonates and infants with ESRD is technically feasible,
can be implemented without major complications, carries a very low rate of CVC
infection and malfunction, and results in adequate nutrition, good growth, as
well as good kidney graft and patient survivals. Future efforts should aim to
prevent hypertension and its cardiac sequelae, improve neurodevelopmental
outcome, and lower mortality rate in these infants.
PMID- 26438040
TI - Epidemiology of infections by HIV, Syphilis, Gonorrhea and Lymphogranuloma
Venereum in Barcelona City: a population-based incidence study.
AB - BACKGROUND: The aim of this study was to determine the evolution of HIV
infection, gonorrhea, syphilis and lymphogranuloma venereum (LGV), and their
epidemiological characteristics in Barcelona city. METHODS: Population-based
incidence study of all newly occurring diagnoses of HIV infection, syphilis,
gonorrhea and LGV detected in Barcelona between January 2007 and December 2011. A
descriptive analysis was performed. The annual incidence rates per 100,000
inhabitants were calculated by sex, sexual conduct and educational level. To
estimate global sex-specific rates we used the Barcelona city census; for the
calculation of rates by sexual conduct and educational level we used estimates of
the Barcelona Health Interview Survey. Trends were analysed using the chi-squared
test for linear trend. RESULTS: HIV. 66.8 % of the HIV cases were men who had sex
with men (MSM). The incidence rates in MSM over the study period were from
692.67/100,000 to 909.88/100,000 inh. Syphilis. 74.2 % of the syphilis cases were
MSM. The incidence rates in MSM were from 224.9/100,000 to 891.97/100,000 inh.
and the MSM with a university education ranged from 196.3/100,000 to
1020.8/100,000. Gonorrhea. 45.5 % of the gonorrhea cases were MSM. The incidence
rates in MSM were from 164.24/100,000 to 404.79/100,000 inh. and the MSM with
university education ranged from 176.7/100,000 to 530.1/100,000 inh..
Lymphogranuloma venereum (LGV). 95.3 % of the LGV cases are MSM. The incidence
rates in MSM were from 24.99/100,000 to 282.99/100,000 inh. and the MSM with
university education ranged from 9.3/100,000 to 265/100,000 inh. CONCLUSION: An
increase in cases of STI was observed. These STI mainly affected MSM with a
university education. Continuing to monitor changes in the epidemiology of STI,
and identifying the most affected groups should permit redesigning preventive
programs, with the goal of finding the most efficient way to reach these
population groups.
PMID- 26438041
TI - Changes in equity of maternal, newborn, and child health care practices in 115
districts of rural Ethiopia: implications for the health extension program.
AB - BACKGROUND: Reducing within-country inequities in the coverage of maternal,
newborn, and child health (MNCH) interventions is essential to improving a
country's maternal and child health and survival rates. The community-based
health extension program (HEP) of Ethiopia, launched in 2003, aims to provide
equitable primary health care services. Since 2008 the Last Ten Kilometers
Project (L10K) has been supporting the HEP in promoting equitable MNCH
interventions in 115 districts covering about 14 million people. We report the
inequities in MNCH programmatic indicators in 2008 and in 2010 in the L10K areas,
along with changes in equity between the two survey periods, and the implications
of these results for the national program. METHODS: The study used cross
sectional surveys of 3932 and 3867 women from 129 representative kebeles
(communities) conducted in December 2008 and December 2010, respectively.
Nineteen HEP outreach activity coverage and MNCH care practice indicators were
calculated for each survey period, stratified by the inequity factors considered
(i.e. age, education, wealth and distance from the nearest health facility). We
calculated relative inequities using concentration indices for each of the
indicators and inequity factors. Ninety-five percent confidence intervals and
survey design adjusted Wald's statistics were used to assess differentials in
equity. RESULTS: Education and age related inequities in the MNCH indicators were
the most prominent (observed for 13 of the 19 outcomes analyzed), followed in
order by wealth inequity (observed for eight indicators), and inequity due to
distance from the nearest health facility (observed for seven indicators). Age
inequities in six of the indicators increased between 2008 and 2010;
nevertheless, there was no consistent pattern of changes in inequities during
that period. Some related issues such as inequities due to wealth in household
visits by the health extension workers and prevalence of modern family household;
and inequities due to education in household visits by community health promoters
showed improvement. CONCLUSIONS: Addressing these inequities in MNCH
interventions by age, education and wealth will contribute significantly toward
achieving Ethiopia's maternal health targets for the Millennium Development Goals
and beyond. HEP will require more innovative strategies to achieve equitable MNCH
services and outcomes and to routinely monitor the effectiveness of those
strategies.
PMID- 26438042
TI - Training Cambodian Village Health Support Guides in Diabetes Prevention: Effects
on Guides' Knowledge and Teaching Activities Over 6 Months.
AB - BACKGROUND: Type 2 diabetes is a pressing public health concern in Cambodia, a
country with limited human resource capacity due to genocide. Cambodian village
health support guides (Guides) promote health at the local level. PURPOSE: This
paper reports preliminary results of training Guides in diabetes prevention.
METHOD: The curriculum, called Eat, Walk, Sleep was delivered to Guides in Siem
Reap province once over 3 h. Participants completed a pretest and posttest on
diabetes knowledge. Guides were offered continuing education through Eat, Walk,
Sleep resources and were encouraged to teach Eat, Walk, Sleep in their villages.
For each of 6 months following their training, Guides completed a checklist
regarding their activities. RESULTS: One hundred eighty-five Guides attended one
of ten trainings. Knowledge scores increased significantly from pretest to
posttest. During 6 months of follow-up, n = 159 Guides (85 %) completed at least
one monthly checklist. Guides reported high rates of uptake and delivery of the
Eat, Walk, Sleep curriculum and moderate rates of continuing education about
diabetes. CONCLUSION: Diabetes prevention in Cambodia is nascent. Guides show
excellent uptake and dissemination of the curriculum. Future research should
examine effect of support for Guide activities and the effect of the curriculum
on villager health behaviors, and ultimately, on rates of type 2 diabetes.
PMID- 26438043
TI - Evaluation of microbial transport during aerobic bioaugmentation of an RDX
contaminated aquifer.
AB - In situ bioaugmentation with aerobic hexahydro-1,3,5-trinitro-1,3,5-triazine
(RDX)-degrading bacteria is being considered for treatment of explosives
contaminated groundwater at Umatilla Chemical Depot, Oregon (UMCD). Two forced
gradient bacterial transport tests of site groundwater containing chloride or
bromide tracer and either a mixed culture of Gordonia sp. KTR9 (xplA (+)Km(R)),
Rhodococcus jostii RHA1 (pGKT2 transconjugant; xplA (+)Km(R)) and Pseudomonas
fluorescens I-C (xenB (+)), or a single culture of Gordonia sp. KTR9 (xplA (+);
i.e. wild-type) were conducted at UMCD. Groundwater monitoring evaluated cell
viability and migration in the injection well and downgradient monitoring wells.
Enhanced degradation of RDX was not evaluated in these demonstrations.
Quantitative PCR analysis of xplA, the kanamycin resistance gene (aph), and xenB
indicated that the mixed culture was transported at least 3 m within 2 h of
injection. During a subsequent field injection of bioaugmented groundwater,
strain KTR9 (wild-type) migrated up to 23-m downgradient of the injection well
within 3 days. Thus, the three RDX-degrading strains were effectively introduced
and transported within the UMCD aquifer. This demonstration represents an
innovative application of bioaugmentation to potentially enhance RDX
biodegradation in aerobic aquifers.
PMID- 26438044
TI - Genomic dissection of the 1994 Cronobacter sakazakii outbreak in a French
neonatal intensive care unit.
AB - BACKGROUND: Cronobacter sakazakii is a member of the genus Cronobacter that has
frequently been isolated from powdered infant formula (PIF) and linked with rare
but fatal neonatal infections such as meningitis and necrotising enterocolitis.
The Cronobacter MLST scheme has reported over 400 sequence types and 42 clonal
complexes; however C. sakazakii clonal complex 4 (CC4) has been linked strongly
with neonatal infections, especially meningitis. There have been a number of
reported Cronobacter outbreaks over the last three decades. The largest outbreak
of C. sakazakii was in a neonatal intensive care unit (NICU) in France (1994)
that lasted over 3 months and claimed the lives of three neonates. The present
study used whole genome sequencing data of 26 isolates obtained from this
outbreak to reveal their relatedness. This study is first of its kind to use
whole genome sequencing data to analyse a Cronobacter outbreak. METHODS: Whole
genome sequencing data was generated for 26 C. sakazakii isolates on the Illumina
MiSeq platform. The whole genome phylogeny was determined using Mugsy and RaxML.
SNP calls were determined using SMALT and SAMtools, and filtered using VCFtools.
RESULTS: The whole genome phylogeny suggested 3 distant clusters of C. sakazakii
isolates were associated with the outbreak. SNP typing and phylogeny indicate the
source of the C. sakazakii could have been from extrinsic contamination of
reconstituted infant formula from the NICU environment and personnel. This pool
of strains would have contributed to the prolonged duration of the outbreak,
which was up to 3 months. Furthermore 3 neonates were co-infected with C.
sakazakii from two different genotype clusters. CONCLUSION: The genomic
investigation revealed the outbreak consisted of an heterogeneous population of
C. sakazakii isolates. The source of the outbreak was not identified, but
probably was due to environmental and personnel reservoirs resulting in extrinsic
contamination of the neonatal feeds. It also indicated that C. sakazakii isolates
from different genotype clusters have the ability to co-infect neonates.
PMID- 26438045
TI - High evolutionary turnover of satellite families in Caenorhabditis.
AB - BACKGROUND: The high density of tandem repeat sequences (satellites) in nematode
genomes and the availability of genome sequences from several species in the
group offer a unique opportunity to better understand the evolutionary dynamics
and the functional role of these sequences. We take advantage of the previously
developed SATFIND program to study the satellites in four Caenorhabditis species
and investigate these questions. METHODS: The identification and comparison of
satellites is carried out in three steps. First we find all the satellites
present in each species with the SATFIND program. Each satellite is defined by
its length, number of repeats, and repeat sequence. Only satellites with at least
ten repeats are considered. In the second step we build satellite families with a
newly developed alignment program. Satellite families are defined by a consensus
sequence and the number of satellites in the family. Finally we compare the
consensus sequence of satellite families in different species. RESULTS: We give a
catalog of individual satellites in each species. We have also identified
satellite families with a related sequence and compare them in different species.
We analyze the turnover of satellites: they increased in size through
duplications of fragments of 100-300 bases. It appears that in many cases they
have undergone an explosive expansion. In C. elegans we have identified a subset
of large satellites that have strong affinity for the centromere protein CENP-A.
We have also compared our results with those obtained from other species,
including one nematode and three mammals. CONCLUSIONS: Most satellite families
found in Caenorhabditis are species-specific; in particular those with long
repeats. A subset of these satellites may facilitate the formation of
kinetochores in mitosis. Other satellite families in C. elegans are either
related to Helitron transposons or to meiotic pairing centers.
PMID- 26438046
TI - Downregulation of ASPP2 in pancreatic cancer cells contributes to increased
resistance to gemcitabine through autophagy activation.
AB - BACKGROUND: Apoptosis-stimulating of p53 protein 2 (ASPP2) is one of the ASPP
family members and it has been reported to be associated with human cancer.
However, the role of it in pancreatic cancer is still not clear. METHODS: We
analyzed the expression level of ASPP2 in cancer tissue samples with RT-qPCR,
Western Blotting assay and immunohistochemistry staining. We studied the
biological function of ASPP2 and its mechanism with gene overexpression and gene
silencing technologies. We determined the sensitivity of pancreatic cells with
differential ASPP2 level to gemcitabine and whether autophagy inhibition affected
the gemcitabine resistance, both in vitro and in vivo. RESULTS: Expression of
ASPP2 was downregulated in cancerous tissues in comparison with para-cancerous
tissues. ASPP2 expression was linked to clinical outcomes in patients and down
regulation of ASPP2 increased cell proliferation, autophagic flux, the activity
of AMP Kinase of pancreatic cancer cells and vice versa. Knockdown of ASPP2
results in increased resistance to gemcitabine, which was attributed to the
enhanced autophagy. CONCLUSIONS: ASSP2 expression is lower in cancerous tissues
and decreased ASPP2 lead to higher cancer cells proliferation and autophagic
flux, which contribute to the gemcitabine resistance.
PMID- 26438047
TI - Genetics analysis of 38 STR loci in Uygur population from Southern Xinjiang of
China.
AB - The allele frequencies and statistical parameters of 38 autosomal short tandem
repeat (STR) loci were analyzed in the Uygur population from Southern Xinjiang of
China with 290 unrelated individuals. The results show these 38 STR loci have
high or medium power of discrimination and probabilities of exclusion. All loci
are in Hardy-Weinberg equilibrium. The genetic distances between the Uygur
population and other Chinese populations were also estimated.
PMID- 26438048
TI - Tumor-induced inflammation alters neutrophil phenotype and disease progression.
AB - Neutrophils are essential to combat infectious agents but contribute to
collateral inflammatory damage. Likewise, neutrophils can kill cancer cells and
have been shown to promote malignant growth and metastasis through
immunosuppressive functions. Two articles in a recent issue of Nature reveal new
mechanisms by which tumors induce changes in neutrophil phenotype through
production of inflammatory cytokines. Although the two studies report different
outcomes on the effects of neutrophils on tumor growth and metastasis, they
delineate novel molecular pathways influencing neutrophil phenotype that may
provide new approaches to harnessing neutrophil functions in the treatment of
cancer.
PMID- 26438049
TI - Isoferulic acid prevents methylglyoxal-induced protein glycation and DNA damage
by free radical scavenging activity.
AB - BACKGROUND: Isoferulic acid (IFA), a naturally occurring cinnamic acid
derivative, is a main active ingredient of the rhizoma of Cimicifuga dahurica. It
has been shown various pharmacological activities. The aim of the study was to
investigate the effect of IFA against MG-induced protein glycation and oxidative
DNA damage. Free radical scavenging activity and the MGO-trapping abilities of
IFA were also investigated. METHODS: The fluorescent MG-derived AGEs and non
fluorescent N(epsilon)-(carboxymethyl) lysine (N(epsilon)-CML) was measured using
a spectrofluorometer and an enzyme linked immunosorbant assay (ELISA). Protein
carbonyl content was used to detect protein oxidation. Gel electrophoresis was
used to determine DNA damage. Superoxide anion radicals and hydroxyl radicals
were determined using cytochrome c reduction assay and thiobarbituric acid
reactive 2-deoxy-D-ribose oxidation products, respectively. The MG-trapping
capacity was performed by HPLC. RESULTS: IFA (1.25-5 mM) inhibited the formation
of fluorescent MG-derived AGEs, and N(epsilon)-CML, and protein carbonyl in
bovine serum albumin. In addition, IFA (0.1-1 mM) also prevented MG/lysine
mediated oxidative DNA damage in the presence and absence of copper ion. The
protective ability of IFA was directly correlated to inhibition of hydroxyl and
superoxide anion radical generation during the reaction of MG and lysine. Most
notably, IFA had no the directly trapping ability to MG. CONCLUSIONS: The present
results highlighted that free radical scavenging activity, but not the MG
trapping ability, is the mechanism of IFA for preventing MG-induced protein
glycation and DNA damage.
PMID- 26438051
TI - Balloon protection of the Labbe vein during transarterial embolization of a dural
arterio-venous fistula.
AB - INTRODUCTION: Endovascular treatment of type III dural arterio-venous fistulas
can be challenging if the fistulous point is close to a functionally important
cortical vein. METHODS: A technique is described for temporary balloon protection
of the vein of Labbe during transarterial Onyx embolization of a type III dural
arterio-venous fistula. One illustrative case is presented. Careful anatomic
consideration of the concerned venous segment (at the insertion point into the
lateral sinus) and the choice of balloon minimized the risk of venous rupture.
RESULTS: Using this method, satisfactory progression of Onyx was obtained within
the arterio-venous shunt while preserving the patency of the Labbe vein.
CONCLUSION: Temporary balloon protection of the Labbe vein is a feasible option
to preserve its patency during embolization of dural arterio-venous fistulas. To
the authors' knowledge, this is the first report on the use of temporary balloon
protection of a cortical vein.
PMID- 26438050
TI - Immunopathogenic Background of Pars Planitis.
AB - Pars planitis is defined as an intermediate uveitis of unknown background of
systemic disease with characteristic formations such as vitreous snowballs,
snowbanks and changes in peripheral retina. The incidence of pars planitis varies
2.4-15.4 % of the uveitis patients. The pathogenesis of the disease is to be
determined in future. Clinical and histopathological findings suggest an
autoimmune etiology, most likely as a reaction to endogenous antigen of unknown
source, with T cells predominant in both vitreous and pars plana infiltrations. T
cells subsets play an important role as a memory-effector peripheral cell.
Snowbanks are formed as an effect of post inflammatory glial proliferation of
fibrous astrocytes. There is also a genetic predisposition for pars planitis by
human leukocyte antigen and several other genes. A coexistence of multiple
sclerosis and optic neuritis has been described in numerous studies. Epiretinal
membrane, cataract, cystoid macular edema, retinal detachment, retinal
vasculitis, neovascularization, vitreous peripheral traction, peripheral hole
formation, vitreous hemorrhage, disc edema are common complications observed in
pars planitis. There is a need to expand the knowledge of the pathogenic and
immunologic background of the pars planitis to create an accurate pharmacological
treatment.
PMID- 26438052
TI - Simple SNP-based minimal marker genotyping for Humulus lupulus L. identification
and variety validation.
AB - BACKGROUND: Hop is an economically important crop for the Pacific Northwest USA
as well as other regions of the world. It is a perennial crop with rhizomatous or
clonal propagation system for varietal distribution. A big concern for growers as
well as brewers is variety purity and questions are regularly posed to public
agencies concerning the availability of genotype testing. Current means for
genotyping are based upon 25 microsatellites that provides relatively accurate
genotyping but cannot always differentiate sister-lines. In addition, numerous
PCR runs (25) are required to complete this process and only a few laboratories
exist that perform this service. A genotyping protocol based upon SNPs would
enable rapid accurate genotyping that can be assayed at any laboratory facility
set up for SNP-based genotyping. The results of this study arose from a larger
project designed for whole genome association studies upon the USDA-ARS hop
germplasm collection consisting of approximately 116 distinct hop varieties and
germplasm (female lines) from around the world. RESULTS: The original dataset
that arose from partial sequencing of 121 genotypes resulted in the
identification of 374,829 SNPs using TASSEL-UNEAK pipeline. After filtering out
genotypes with more than 50% missing data (5 genotypes) and SNP markers with more
than 20% missing data, 32,206 highly filtered SNP markers across 116 genotypes
were identified and considered for this study. Minor allele frequency (MAF) was
calculated for each SNP and ranked according to the most informative to least
informative. Only those markers without missing data across genotypes as well as
60% or less heterozygous gamete calls were considered for further analysis.
Genetic distances among individuals in the study were calculated using the marker
with the highest MAF value, then by using a combination of the two markers with
highest MAF values and so on. This process was reiterated until a set of markers
was identified that allowed for all genotypes in the study to be genetically
differentiated from each other. Next, we compared genetic matrices calculated
from the minimal marker sets [(Table 2; 6-, 7-, 8-, 10- and 12-marker set
matrices] and that of a matrix calculated from a set of markers with no missing
data across all 116 samples (1006 SNP markers). The minimum number of markers
required to meet both specifications was a set of 7-markers (Table 3). These
seven SNPs were then aligned with a genome assembly, and DNA sequence both
upstream and downstream were used to identify primer sequences that can be used
to develop seven amplicons for high resolution melting curve PCR detection or
other SNP-based PCR detection methods. CONCLUSIONS: This study identifies a set
of 7 SNP markers that may prove useful for the identification and validation of
hop varieties and accessions. Variety validation of unknown samples assumes that
the variety under question has been included a priori in a discovery panel. These
results are based upon in silica studies and markers need to be validated using
different SNP marker technology upon a differential set of hop genotypes. The
marker sequence data and suggested primer sets provide potential means to
fingerprint hop varieties in most genetic laboratories utilizing SNP-marker
technology.
PMID- 26438053
TI - Alveolar macrophages support interferon gamma-mediated viral clearance in RSV
infected neonatal mice.
AB - BACKGROUND: Poor interferon gamma (IFNgamma) production during respiratory
syncytial virus (RSV) is associated with prolonged viral clearance and increased
disease severity in neonatal mice and humans. We previously showed that intra
nasal delivery of IFNgamma significantly enhances RSV clearance from neonatal
lungs prior to observed T-lymphocyte recruitment or activation, suggesting an
innate immune mechanism of viral clearance. We further showed that alveolar
macrophages dominate the RSV-infected neonatal airways relative to adults,
consistent with human neonatal autopsy data. Therefore, the goal of this work was
to determine the role of neonatal alveolar macrophages in IFNgamma-mediated RSV
clearance. METHODS: Clodronate liposomes, flow cytometry, viral plaque assays,
and histology were used to examine the role of alveolar macrophages (AMs) and the
effects of intra-nasal IFNgamma in RSV infected neonatal Balb/c mice. The
functional outcomes of AM depletion were determined quantitatively by viral
titers using plaque assay. Illness was assessed by measuring reduced weight gain.
RESULTS: AM activation during RSV infection was age-dependent and correlated
tightly with IFNgamma exposure. Higher doses of IFNgamma more efficiently
stimulated AM activation and expedited RSV clearance without significantly
affecting weight gain. The presence of AMs were independently associated with
improved RSV clearance, whereas AM depletion but not IFNgamma exposure,
significantly impaired weight gain in RSV-infected neonates. CONCLUSION: We show
here for the first time, that IFNgamma is critical for neonatal RSV clearance and
that it depends, in part, on alveolar macrophages (AMs) for efficient viral
clearing effects. Early reductions in viral burden are likely to have profound
short- and long-term immune effects in the vulnerable post-natally developing
lung environment. Studies are ongoing to elucidate the pathologic effects
associated with early versus delayed RSV clearance in developing neonatal
airways.
PMID- 26438055
TI - A series of abnormal climatic conditions caused the most severe outbreak of first
generation adults of the meadow moth (Loxostege sticticalis L.) in China.
AB - The meadow moth, Loxostege sticticalis L., is a destructive migratory pest in the
northern temperate zone. The outbreak mechanism of first-generation adults in
China remains unclear. In 2008, the density of first-generation larvae was very
low or even negligible in most sites in China. However, a great number of first
generation adults appeared unexpectedly in late July, and their offspring caused
the most severe infestation on record. The present study aims to determine where
the large influx of immigrant adults originated from and how this unprecedented
population was established. Source areas were explored by trajectory analysis,
and climatic patterns related to the population increase were investigated.
Results showed that the outbreak population mainly immigrated from Northeast
Mongolia and the Chita State of Russia, and the buildup of such a large
population could be attributed to an exceptional northward migration of
overwintered adults from North China to East Mongolia in the spring of 2007 and
unusually favourable climatic conditions in the next two growth seasons. These
results indicated that the population dynamics of meadow moth in Northeast Asia
would be difficult to predict when only considering local climatic factors and
population size within one country. International joint monitoring and
information sharing related to this pest between China, Mongolia and Russia
should be implemented.
PMID- 26438054
TI - Neuregulin1-beta decreases interleukin-1beta-induced RhoA activation, myosin
light chain phosphorylation, and endothelial hyperpermeability.
AB - Neuregulin-1 (NRG1) is an endogenous growth factor with multiple functions in the
embryonic and postnatal brain. The NRG1 gene is large and complex, transcribing
more than twenty transmembrane proteins and generating a large number of isoforms
in tissue and cell type-specific patterns. Within the brain, NRG1 functions have
been studied most extensively in neurons and glia, as well as in the peripheral
vasculature. Recently, NRG1 signaling has been found to be important in the
function of brain microvascular endothelial cells, decreasing IL-1beta-induced
increases in endothelial permeability. In the current experiments, we have
investigated the pathways through which the NRG1-beta isoform acts on IL-1beta
induced endothelial permeability. Our data show that NRG1-beta increases barrier
function, measured by transendothelial electrical resistance, and decreases IL
1beta-induced hyperpermeability, measured by dextran-40 extravasation through a
monolayer of brain microvascular endothelial cells plated on transwells. An
investigation of key signaling proteins suggests that the effect of NRG1-beta on
endothelial permeability is mediated through RhoA activation and myosin light
chain phosphorylation, events which affect filamentous actin morphology. In
addition, AG825, an inhibitor of the erbB2-associated tyrosine kinase, reduces
the effect of NRG1-beta on IL-1beta-induced RhoA activation and myosin light
chain phosphorylation. These data add to the evidence that NRG1-beta signaling
affects changes in the brain microvasculature in the setting of
neuroinflammation. We propose the following events for neuregulin-1-mediated
effects on Interleukin-1 beta (IL-1beta)-induced endothelial hyperpermeability:
IL-1beta leads to RhoA activation, resulting in an increase in phosphorylation of
myosin light chain (MLC). Phosphorylation of MLC is known to result in actin
contraction and alterations in the f-actin cytoskeletal structure. These changes
are associated with increased endothelial permeability. Neuregulin-1beta acts
through its transmembrane receptors to activate intracellular signaling pathways
which inhibit IL-1beta-induced RhoA activation and MLC phosphorylation, thereby
preserving the f-actin cytoskeletal structure and endothelial barrier function.
PMID- 26438056
TI - Rationale and methods for a randomized controlled trial of a movement-to-music
video program for decreasing sedentary time among mother-child pairs.
AB - BACKGROUND: Measured objectively, under a quarter of adults and fewer than half
of preschool children meet the criteria set in the aerobic physical activity
recommendations of the Centers for Disease Control and Prevention. Moreover,
adults reportedly are sedentary (seated or lying down) for most of their waking
hours. Importantly, greater amounts of sedentary time on parents' part are
associated with an increased risk of more sedentary time among their children. A
randomized controlled trial targeting mother-child pairs has been designed, to
examine whether a movement-to-music video program may be effective in reducing
sedentary time and increasing physical activity in the home environment. METHODS:
Mother-child pairs (child age of 4-7 years) will be recruited from among NELLI
lifestyle-modification study five-year follow-up cohort participants,
encompassing 14 municipalities in Pirkanmaa region, Finland. Accelerometer and
exercise diary data are to be collected for intervention and control groups at
the first, second and eighth week after the baseline measurements. Background
factors, physical activity, screen time, motivation to exercise, and self
reported height and weight, along with quality of life, will be assessed via
questionnaires. After the baseline and first week measurements, the participants
of the intervention group will receive a movement-to-music video program designed
to reduce sedentary time and increase physical activity. Intervention group
mother-child pairs will be instructed to exercise every other day while watching
the video program over the next seven weeks. Information on experiences of the
use of the movement-to-music video program will be collected 8 weeks after
baseline. Effects of the intervention will be analyzed in line with the intention
to-treat principle through comparison of the changes in the main outcomes between
intervention and control group participants. The study has received ethics
approval from the Pirkanmaa Ethics Committee in Human Sciences. DISCUSSION: The
study will yield information on the effectiveness of movement-to-music video
exercise in reducing sedentary behavior. Intervention-based methods have proven
effective in increasing physical activity in home environments. Music may improve
exercise adherence, which creates a possibility of achieving long-term health
benefits. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov, as
NCT02270138. It was registered on October 2, 2014.
PMID- 26438057
TI - Core domain mutant Y220C of p53 protein has a key role in copper homeostasis in
case of free fatty acids overload.
AB - Nonalcoholic fatty liver disease (NAFLD) is a pathology that includes a wide
variety of clinical conditions ranging from simple steatosis to end-stage liver
diseases. Despite the huge amount of researches, the molecular basis of NAFLD are
still not fully understood. Recently, it was suggested a role for p53 in NAFLD
pathogenesis. Among its targets there is Synthesis of Cytochrome c Oxidase 2
(SCO2), a copper chaperone, involved in both aerobic respiration and metal
cellular excretion. Copper seems to play a role in NAFLD. It was demonstrated a
low hepatic copper content in NAFLD patients, which correlates with metabolic
syndrome parameters. Copper homeostasis deregulation, in fact, seems to be
related to lipid metabolism alteration and insulin resistance. Here we provide
evidence on the role of p53 in the modulation of copper homeostasis, in an
experimental model of NAFLD. We used two different hepatoma cell lines, HepG2 and
Huh 7.5.1, characterized by the presence of wt p53 and its Y220C mutant,
respectively, treated with a free fatty acids (FFAs) solution. Interestingly, p53
activation correlated with the intracellular copper level maintenance. We
demonstrated that, in hepatoma cell lines, core domain mutant Y220C of p53
affects the modulation of SCO2 and Copper transporter 1 (CTR1), influencing, in
this way, intracellular copper homeostasis in presence of FFAs accumulation, and
that the 220 residue of the protein is crucial for such control. The role of p53
we highlighted may have deep implications in clinical conditions where copper
homeostasis is deregulated.
PMID- 26438058
TI - Maternal risk factors and perinatal outcomes among pacific islander groups in
Hawaii: a retrospective cohort study using statewide hospital data.
AB - BACKGROUND: Studies suggest Pacific Islander women have disparate rates of
preterm birth, primary cesarean delivery, preeclampsia, gestational diabetes, and
low birthweight infants. However, data is limited. In order to improve the health
of Pacific Islanders, it is essential to better understand differences in
obstetric outcomes in this diverse population METHODS: This study compared
perinatal outcomes between Pacific Islander (9,646) and White (n = 5,510) women
who delivered a singleton liveborn in any Hawaii hospital from January 2010 to
December 2011 using the Hawaii Health Information Corporation (HHIC) database.
Pacific Islanders were disaggregated into the following groups: Native Hawaiian,
Samoan, Micronesian, and Other Pacific Islanders. Perinatal outcomes (e.g.
hypertensive diseases, birthweight, mode of delivery) were compared using
multivariable logistic models controlling for relevant sociodemographic and
health risk factors (e.g. age and payer type). RESULTS: Significant differences
in perinatal outcomes between Pacific Islander and White women and newborns were
noted. All Pacific Islander groups had an increased risk of hypertension. Outcome
differences were also seen between Pacific Islanders groups. Native Hawaiians had
the highest risk of low birthweight infants, Samoans had the highest risk of
macrosomic infants and Micronesians had the highest risk of cesarean delivery.
CONCLUSIONS: Important differences in perinatal outcomes among Pacific Islanders
exist. It is important to examine Pacific Islander populations separately in
future research, public health interventions, and policy.
PMID- 26438059
TI - Diagnostic value of soluble receptor-binding cancer antigen expressed on SiSo
cells and carcinoembryonic antigen in differentiating malignant from benign
pleural effusion.
AB - Diagnosis of malignant pleural effusion (MPE) remains a major clinical challenge.
The aim of this study was to evaluate the diagnostic value of combined detection
of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) and
carcinoembryonic antigen (CEA) in patients with MPE and benign pleural effusion
(BPE). The serum and pleural fluid samples were collected from 53 patients
diagnosed with MPE and 49 patients with BPE. Enzyme-linked immunosorbent assay
was used to detect the concentration of RCAS1 in serum and pleural effusion. The
clinical data and laboratory information, including CEA levels, were gathered
from these cases. The concentration of RCAS1 in MPE was significantly higher than
that of BPE (P < 0.001). There was no significant difference between the two
serum groups. The diagnostic sensitivity and specificity of pleural fluid RCAS1
were 67.92 and 81.63 %, respectively, at the optimized cutoff value of 7.326
U/mL; meanwhile, the sensitivity and specificity of pleural fluid CEA were 83.02
and 91.84 % at the cutoff value of 3.93 ng/mL. The specificity could be elevated
to 98.50 % in serial detection, while the sensitivity may be improved to 94.55 %
in parallel detection. Serum RCAS1 concentration was only detected in 53 serum
samples out of the 102 samples, indicating that serum RCAS1 may not be a better
option in differential diagnosis of malignancies compared with serum CEA, of
which the diagnostic sensitivity and specificity were 64.15 and 83.67 % at the
cutoff value of 3.90 ng/mL. No significant differences were found in pleural
fluid RCAS1 concentration in MPE patients with different ages, gender, and
pathological types of lung cancers. The detection of RCAS1 concentration in
pleural fluid is informative for the diagnosis of MPE. Joint detection of RCAS1
and CEA can improve the diagnostic sensitivity and specificity. However, the
diagnostic value of RCAS1 is not higher than that of CEA.
PMID- 26438060
TI - Polymorphisms of 5,10-methylenetetrahydrofolate reductase and thymidylate
synthase, dietary folate intake, and the risk of leukemia in adults.
AB - The 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase
(TS) are critical enzymes in folate metabolism. Previous studies have reported
conflicting results on the associations between MTHFR/TS polymorphisms and adult
leukemia risk, which may due to the lack of information on folate intake. We
investigated the risks of adult leukemia with genetic polymorphisms of folate
metabolic enzymes (MTHFR C677T, A1298C, and TS) and evaluated if the associations
varied by dietary folate intake from a multicenter case-control study conducted
in Chinese. This study comprised 442 incident adult leukemia cases and 442
outpatient controls, individually matched to cases by gender, birth quinquennium,
and study site. Genotypes were determined by a polymerase chain reaction (PCR) or
PCR-based restriction fragment length polymorphism assay. Dietary folate intake
was assessed by face-to-face interviews using a validated food-frequency
questionnaire. The MTHFR 677TT genotype conferred a significant higher risk of
leukemia in males than in females and exhibited an increased risk of acute
myeloid leukemia (AML) but a decreased risk of acute lymphoblastic leukemia
(ALL). The MTHFR 1298AC genotype appeared to decrease the risks of leukemia in
both genders, in AML and ALL. Stratified analysis by dietary folate intake showed
the increased risks of leukemia with the MTHFR 677TT and TS 2R3R/2R2R genotypes
were only significant in individuals with low folate intake. A significant
interaction between TS polymorphism and dietary folate intake was observed (P =
0.03). This study suggests that dietary folate intake and gender may modify the
associations between MTHFR/TS polymorphisms and adult leukemia risk.
PMID- 26438061
TI - Significance of Onodera's prognostic nutritional index in patients with
colorectal cancer: a large cohort study in a single Chinese institution.
AB - The preoperative nutritional and immunological statuses have an important impact
in predicting the survival outcome of patients with various types of malignant
tumors. Our study aimed to explore the clinical significance and predictive
prognostic potential of Onodera's prognostic nutritional index (PNI) in patients
with colorectal carcinoma. This retrospective study included a total of 1321
patients who were diagnosed with colorectal cancer and who had been surgically
treated between January 1994 and December 2007. The PNI level was determined
according the following formula: 10 * serum albumin (g/dL) + 0.005 * total
lymphocyte count (per mm(3)). The impact of PNI on clinicopathological features
and overall survival (OS) was determined. The optimal cutoff value of PNI was set
at 45. Patients in the low-PNI group had a greater potential to have aggressive
histological features, advanced tumors (T), nodal involvement (N), metastasis
(M), and TNM stage than those in the high-PNI group. The low-PNI group had a
worse OS than the high-PNI group (5-year survival rate 56.1 vs 64.8 %,
respectively; P < 0.05). Furthermore, the PNI value was an independent prognostic
factor for colorectal cancer in this study. The OS was significantly lower in the
low-PNI group than in the high-PNI group in patients with TNM stage II and III
diseases. Preoperative PNI is a simple and useful marker to predict
clinicopathological features and long-term survival outcome in patients with
colorectal carcinoma. PNI analysis should be included in the routine assessment
of patients with locally advanced colorectal cancer.
PMID- 26438062
TI - Increased expression of C-C motif ligand 2 associates with poor prognosis in
patients with gastric cancer after gastrectomy.
AB - Previous studies have demonstrated the clinical significance of polarized tumor
associated macrophages (TAMs) in gastric cancer whereas the cytokines
orchestrating TAM polarization remain elusive. This study aims to evaluate the
prognostic value of C-C motif ligand 2 (CCL2) expression in gastric cancer
patients after surgery. We examined CCL2 expression in tumor tissues by
immunohistochemical staining in retrospectively enrolled 414 gastric cancer
patients receiving gastrectomy at Zhongshan Hospital during 2008. We used Kaplan
Meier analysis and Cox regression models to assess the prognostic value of CCL2
expression. We generated a predictive nomogram from integrating CCL2 expression
with the TNM staging system to evaluate 3- and 5-year overall survival. High
intratumor CCL2 expression associated with adverse clinical outcome. Intratumor
CCL2 expression provided additional prognostic value in gastric cancer patients.
CCL2 expression, as well as well-established TNM staging parameters, was
identified as independent prognostic factor for overall survival. The generated
nomogram corresponded well with the ideal model in predicting the 3- and 5-year
overall survival of gastric cancer patients. CCL2, an identified potential
independent adverse prognosticator, could be integrated with TNM staging system
to improve the predictive accuracy for overall survival in gastric cancer
patients especially with advanced stages.
PMID- 26438063
TI - Fibronectin-, vitronectin- and laminin-binding proteins at the cell walls of
Candida parapsilosis and Candida tropicalis pathogenic yeasts.
AB - BACKGROUND: Candida parapsilosis and C. tropicalis increasingly compete with C.
albicans-the most common fungal pathogen in humans-as causative agents of severe
candidiasis in immunocompromised patients. In contrast to C. albicans, the
pathogenic mechanisms of these two non-albicans Candida species are poorly
understood. Adhesion of Candida yeast to host cells and the extracellular matrix
is critical for fungal invasion of hosts. METHODS: The fungal proteins involved
in interactions with extracellular matrix proteins were isolated from mixtures of
beta-1,3-glucanase- or beta-1,6-glucanase-extractable cell wall-associated
proteins by use of affinity chromatography and chemical cross-linking methods,
and were further identified by liquid chromatography-coupled tandem mass
spectrometry. RESULTS: In the present study, we characterized the binding of
three major extracellular matrix proteins--fibronectin, vitronectin and laminin-
to C. parapsilosis and C. tropicalis pseudohyphae. The major individual compounds
of the fungal cell wall that bound fibronectin, vitronectin and laminin were
found to comprise two groups: (1) true cell wall components similar to C.
albicans adhesins from the Als, Hwp and Iff/Hyr families; and (2) atypical
(cytoplasm-derived) surface-exposed proteins, including malate synthase, glucose
6-phosphate isomerase, 6-phosphogluconate dehydrogenase, enolase, fructose-1,6
bisphosphatase, transketolase, transaldolase and elongation factor 2. DISCUSSION:
The adhesive abilities of two investigated non-albicans Candida species toward
extracellular matrix proteins were comparable to those of C. albicans suggesting
an important role of this particular virulence attribute in the pathogenesis of
infections caused by C. tropicalis and C. parapsilosis. CONCLUSIONS: Our results
reveal new insight into host-pathogen interactions during infections by two
important, recently emerging, fungal pathogens.
PMID- 26438064
TI - Weathering the storm: parental effort and experimental manipulation of stress
hormones predict brood survival.
AB - BACKGROUND: Unpredictable and inclement weather is increasing in strength and
frequency, challenging organisms to respond adaptively. One way in which animals
respond to environmental challenges is through the secretion of glucocorticoid
stress hormones. These hormones mobilize energy stores and suppress non-essential
physiological and behavioral processes until the challenge passes. To investigate
the effects of glucocorticoids on reproductive decisions, we experimentally
increased corticosterone levels (the primary glucocorticoid in birds) in free
living female tree swallows, Tachycineta bicolor, during the chick-rearing stage.
Due to an unprecedented cold and wet breeding season, 90 % of the nests in our
study population failed, which created a unique opportunity to test how
challenging environmental conditions interact with the physiological mechanisms
underlying life-history trade-offs. RESULTS: We found that exogenous
corticosterone influenced the regulation of parental decisions in a context
dependent manner. Control and corticosterone-treated females had similar brood
failure rates under unfavorable conditions (cold and rainy weather), but
corticosterone treatment hastened brood mortality under more favorable
conditions. Higher female nest provisioning rates prior to implantation were
associated with increased probability of brood survival for treatment and control
groups. However, higher pre-treatment male provisioning rates were associated
with increased survival probability in the control group, but not the
corticosterone-treated group. CONCLUSIONS: These findings reveal complex
interactions between weather, female physiological state, and partner parental
investment. Our results also demonstrate a causal relationship between
corticosterone concentrations and individual reproductive behaviors, and point to
a mechanism for why naturally disturbed populations, which experience multiple
stressors, could be more susceptible and unable to respond adaptively to changing
environmental conditions.
PMID- 26438066
TI - Standing genetic variation as a major contributor to adaptation in the Virginia
chicken lines selection experiment.
AB - BACKGROUND: Artificial selection provides a powerful approach to study the
genetics of adaptation. Using selective-sweep mapping, it is possible to identify
genomic regions where allele-frequencies have diverged during selection. To avoid
false positive signatures of selection, it is necessary to show that a sweep
affects a selected trait before it can be considered adaptive. Here, we confirm
candidate, genome-wide distributed selective sweeps originating from the standing
genetic variation in a long-term selection experiment on high and low body weight
of chickens. RESULTS: Using an intercross between the two divergent chicken
lines, 16 adaptive selective sweeps were confirmed based on their association
with the body weight at 56 days of age. Although individual additive effects were
small, the fixation for alternative alleles across the loci contributed at least
40 % of the phenotypic difference for the selected trait between these lines. The
sweeps contributed about half of the additive genetic variance present within and
between the lines after 40 generations of selection, corresponding to a
considerable portion of the additive genetic variance of the base population.
CONCLUSIONS: Long-term, single-trait, bi-directional selection in the Virginia
chicken lines has resulted in a gradual response to selection for extreme
phenotypes without a drastic reduction in the genetic variation. We find that
fixation of several standing genetic variants across a highly polygenic genetic
architecture made a considerable contribution to long-term selection response.
This provides new fundamental insights into the dynamics of standing genetic
variation during long-term selection and adaptation.
PMID- 26438067
TI - Hypovolemic men and women regulate blood pressure differently following exposure
to artificial gravity.
AB - PURPOSE: In addition to serious bone, vestibular, and muscle deterioration, space
flight leads to cardiovascular dysfunction upon return to gravity. In seeking a
countermeasure to space flight-induced orthostatic intolerance, we previously
determined that exposure to artificial gravity (AG) training in a centrifuge
improved orthostatic tolerance of ambulatory subjects. This protocol was more
effective in men than women and more effective when subjects exercised. METHODS:
We now determine the orthostatic tolerance limit (OTL) of cardiovascularly
deconditioned (furosemide) men and women on one day following 90 min of AG
compared to a control day (90 min of head-down bed rest, HDBR). RESULTS: There
were three major findings: a short bout of artificial gravity improved
orthostatic tolerance of hypovolemic men (30 %) and women (22 %). Men and women
demonstrated different mechanisms of cardiovascular regulation on AG and HDBR
days; women maintained systolic blood pressure the same after HDBR and AG
exposure while men's systolic pressure dropped (11 +/- 2.9 mmHg) after AG. Third,
as presyncopal symptoms developed, men's and women's cardiac output and stroke
volume dropped to the same level on both days, even though the OTL test lasted
significantly longer on the AG day, indicating cardiac filling as a likely
variable to trigger presyncope. CONCLUSIONS: (1) Even with gender differences, AG
should be considered as a space flight countermeasure to be applied to astronauts
before reentry into gravity, (2) men and women regulate blood pressure during an
orthostatic stress differently following exposure to artificial gravity and (3)
the trigger for presyncope may be cardiac filling.
PMID- 26438065
TI - P-cadherin and the journey to cancer metastasis.
AB - P-cadherin is a classical cell-to-cell adhesion molecule with a homeostatic
function in several normal tissues. However, its behaviour in the malignant
setting is notably dependent on the cellular context. In some tumour models, such
as melanoma and oral squamous cell carcinoma, P-cadherin acts as a tumour
suppressor, since its absence is associated with a more aggressive cancer cell
phenotype; nevertheless, the overexpression of this molecule is linked to
significant tumour promoting effects in the breast, ovarian, prostate,
endometrial, skin, gastric, pancreas and colon neoplasms. Herein, we review the
role of P-cadherin in cancer cell invasion, as well as in loco-regional and
distant metastatic dissemination. We focus in P-cadherin signalling pathways that
are activated to induce invasion and metastasis, as well as cancer stem cell
properties. The signalling network downstream of P-cadherin is notably dependent
on the cellular and tissue context and includes the activation of integrin
molecules, receptor tyrosine kinases, small molecule GTPases, EMT transcription
factors, and crosstalk with other cadherin family members. As new oncogenic
molecular pathways mediated by P-cadherin are uncovered, putative therapeutic
options can be tested, which will allow for the targeting of invasion or
metastatic disease, depending on the tumour model.
PMID- 26438069
TI - Editorial: From Extended Spectrum beta-Lactamases to Carbapenemase: The Never
Ending Challenge Against Gram-Negative Bacteria.
PMID- 26438068
TI - The effect of prior walking on coronary heart disease risk markers in South Asian
and European men.
AB - PURPOSE: Heart disease risk is elevated in South Asians possibly due to impaired
postprandial metabolism. Running has been shown to induce greater reductions in
postprandial lipaemia in South Asian than European men, but the effect of walking
in South Asians is unknown. METHODS: Fifteen South Asian and 14 white European
men aged 19-30 years completed two, 2-day trials in a randomised crossover
design. On day 1, participants rested (control) or walked for 60 min at
approximately 50 % maximum oxygen uptake (exercise). On day 2, participants
rested and consumed two high-fat meals over a 9-h period during which 14 venous
blood samples were collected. RESULTS: South Asians exhibited higher postprandial
triacylglycerol [geometric mean (95 % confidence interval) 2.29 (1.82 to 2.89)
vs. 1.54 (1.21 to 1.96) mmol L(-1) h(-1)], glucose [5.49 (5.21 to 5.79) vs. 5.05
(4.78 to 5.33) mmol L(-1) h(-1)], insulin [32.9 (25.7 to 42.1) vs. 18.3 (14.2 to
23.7) uU mL(-1) h(-1)] and interleukin-6 [2.44 (1.61 to 3.67) vs. 1.04 (0.68 to
1.59) pg mL(-1) h(-1)] than Europeans (all ES >= 0.72, P <= 0.03). Between-group
differences in triacylglycerol, glucose and insulin were not significant after
controlling for age and percentage body fat. Walking reduced postprandial
triacylglycerol [1.79 (1.52 to 2.12) vs. 1.97 (1.67 to 2.33) mmol L(-1) h(-1)]
and insulin [21.0 (17.0 to 26.0) vs. 28.7 (23.2 to 35.4) uU mL(-1) h(-1)] (all ES
>= 0.23. P <= 0.01), but group differences were not significant. CONCLUSIONS:
Healthy South Asians exhibited impaired postprandial metabolism compared with
white Europeans, but these differences were diminished after controlling for
potential confounders. The small-moderate reduction in postprandial
triacylglycerol and insulin after brisk walking was not different between the
ethnicities.
PMID- 26438070
TI - Acute liver failure and seizures as a consequence of regorafenib exposure in
advanced rectal cancer.
AB - BACKGROUND: Regorafenib is a multi-targeted tyrosine kinase inhibitor approved
for use in refractory colorectal cancer. We report the first case of seizures
secondary to acute liver failure, shortly after initiation of regorafenib in a
patient with advanced rectal carcinoma. CASE PRESENTATION: A 64 year-old
Caucasian female presented with confusion and generalized tonic-clonic seizures,
5 days after initiation of regorafenib for advanced rectal cancer. Investigations
revealed significant elevations in bilirubin and alanine aminotransferase. No
other cause for seizures and liver dysfunction were found. After interruption of
regorafenib, no further seizures occurred, the symptoms of confusion resolved and
liver function returned to normal. CONCLUSIONS: We report the first case of
regorafenib-induced acute liver failure resulting in seizures. We suggest early
monitoring for side effects, both clinically and biochemically after initiation
of regorafenib.
PMID- 26438071
TI - IMRT and 3D conformal radiotherapy with or without elective nodal irradiation in
locally advanced NSCLC: A direct comparison of PET-based treatment planning.
AB - AIM: The potential of intensity-modulated radiation therapy (IMRT) as opposed to
three-dimensional conformal radiotherapy (3D-CRT) is analyzed for two different
concepts of fluorodeoxyglucose positron emission tomography (FDG PET)-based
target volume delineation in locally advanced non-small cell lung cancer (LA
NSCLC): involved-field radiotherapy (IF-RT) vs. elective nodal irradiation (ENI).
METHODS: Treatment planning was performed for 41 patients with LA-NSCLC, using
four different planning approaches (3D-CRT-IF, 3D-CRT-ENI, IMRT-IF, IMRT-ENI).
ENI included a boost irradiation after 50 Gy. For each plan, maximum dose
escalation was calculated based on prespecified normal tissue constraints. The
maximum prescription dose (PD), tumor control probability (TCP), conformal
indices (CI), and normal tissue complication probabilities (NTCP) were analyzed.
RESULTS: IMRT resulted in statistically significant higher prescription doses for
both target volume concepts as compared with 3D-CRT (ENI: 68.4 vs. 60.9 Gy, p <
0.001; IF: 74.3 vs. 70.1 Gy, p < 0.03). With IMRT-IF, a PD of at least 66 Gy was
achieved for 95 % of all plans. For IF as compared with ENI, there was a
considerable theoretical increase in TCP (IMRT: 27.3 vs. 17.7 %, p < 0.00001; 3D
CRT: 20.2 vs. 9.9 %, p < 0.00001). The esophageal NTCP showed a particularly good
sparing with IMRT vs. 3D-CRT (ENI: 12.3 vs. 30.9 % p < 0.0001; IF: 15.9 vs. 24.1
%; p < 0.001). CONCLUSION: The IMRT technique and IF target volume delineation
allow a significant dose escalation and an increase in TCP. IMRT results in an
improved sparing of OARs as compared with 3D-CRT at equivalent dose levels.
PMID- 26438072
TI - Reaching their potential: Perceived impact of a collaborative academic-clinical
partnership programme for early career nurses in New Zealand.
AB - BACKGROUND: The dynamic nature of healthcare ensures that early career nurses
enter an uncertain and complex world of practice and consequently require support
to develop their practice, build confidence and reach their potential. The New
Zealand Nurse Entry to Practice programme for registered nurses in their first
year of practice has been operating since 2005 to enable safe and confident
practice, improve the quality of care, and positively impact on recruitment and
retention. This academic and clinical programme was offered as a partnership
between a university and a clinical provider with postgraduate academic credits
gained. AIM: The aim of this study was to explore the perceived impact of
postgraduate university education for early career nurses in one regional health
area of New Zealand. METHODS: Participants were registered nurses who had
completed the early career nurse programme and their clinical preceptors. The
research was conducted via an online survey of 248 nurses and three focus groups
to explore how the programme was experienced and its impact on knowledge and
practice. RESULTS: Early career nurses and their preceptors found that the
programme enables improved knowledge and skills of patient assessment,
application of critical thinking to clinical practice, perceived improvement in
patient care delivery and outcomes, enhanced interprofessional communication and
knowledge sharing, and had a positive impact on professional awareness and career
planning. CONCLUSIONS: This clinical-academic partnership positively impacted on
the clinical practice and transition experience of early career nurses and was
closely aligned to an organization's strategic plan for nursing workforce
development.
PMID- 26438073
TI - An evaluation of the effectiveness of a planned training program for nurses on
administering intramuscular injections into the ventrogluteal site.
AB - BACKGROUND: Nurses commonly use the dorsogluteal area for administering
intramuscular injections. Since the dorsogluteal area has the potential of
leading to serious complications, the ventrogluteal area is recommended as the
best alternative. OBJECTIVE: This study was carried out to determine the level of
knowledge nurses have about the ventrogluteal site and the effects of the
training provided in this context. METHOD AND DESIGN: The study was of quasi
experimental design with a single group based on a pre-test/post-test time
sequence and was conducted with 81 nurses who consented to participate in the
research at a University Hospital. Data in the research were collected with a
questionnaire on the identifying features of the nurses and a questionnaire that
contained statements about the ventrogluteal area. RESULTS: The results of the
study revealed that before the training, 76.5% of the nurses most commonly used
the dorsogluteal area and 7.4% the ventrogluteal region. Four months after the
training, however, it was found that the rate of nurses using the dorsogluteal
area had fallen (48.1%) while the rate of using the ventrogluteal site rose
(34.6%). It was seen that there was a significant difference between the nurses'
pre-training and post-training knowledge scores and their scores four months
after the training. CONCLUSION: It was concluded that the training offered the
nurses about the ventrogluteal area had a positive impact on their knowledge and
practices and that the nurses came away from the training with raised awareness
about the subject and an increased level of knowledge.
PMID- 26438074
TI - Atlas-based analysis of 4D flow CMR: automated vessel segmentation and flow
quantification.
AB - BACKGROUND: Flow volume quantification in the great thoracic vessels is used in
the assessment of several cardiovascular diseases. Clinically, it is often based
on semi-automatic segmentation of a vessel throughout the cardiac cycle in 2D
cine phase-contrast Cardiovascular Magnetic Resonance (CMR) images. Three
dimensional (3D), time-resolved phase-contrast CMR with three-directional
velocity encoding (4D flow CMR) permits assessment of net flow volumes and flow
patterns retrospectively at any location in a time-resolved 3D volume. However,
analysis of these datasets can be demanding. The aim of this study is to develop
and evaluate a fully automatic method for segmentation and analysis of 4D flow
CMR data of the great thoracic vessels. METHODS: The proposed method utilizes
atlas-based segmentation to segment the great thoracic vessels in systole, and
registration between different time frames of the cardiac cycle in order to
segment these vessels over time. Additionally, net flow volumes are calculated
automatically at locations of interest. The method was applied on 4D flow CMR
datasets obtained from 11 healthy volunteers and 10 patients with heart failure.
Evaluation of the method was performed visually, and by comparison of net flow
volumes in the ascending aorta obtained automatically (using the proposed
method), and semi-automatically. Further evaluation was done by comparison of net
flow volumes obtained automatically at different locations in the aorta,
pulmonary artery, and caval veins. RESULTS: Visual evaluation of the generated
segmentations resulted in good outcomes for all the major vessels in all but one
dataset. The comparison between automatically and semi-automatically obtained net
flow volumes in the ascending aorta resulted in very high correlation (r
(2)=0.926). Moreover, comparison of the net flow volumes obtained automatically
in other vessel locations also produced high correlations where expected:
pulmonary trunk vs. proximal ascending aorta (r (2)=0.955), pulmonary trunk vs.
pulmonary branches (r (2)=0.808), and pulmonary trunk vs. caval veins (r
(2)=0.906). CONCLUSIONS: The proposed method allows for automatic analysis of 4D
flow CMR data, including vessel segmentation, assessment of flow volumes at
locations of interest, and 4D flow visualization. This constitutes an important
step towards facilitating the clinical utility of 4D flow CMR.
PMID- 26438075
TI - Prospectively defined murine mesenchymal stem cells inhibit Klebsiella pneumoniae
induced acute lung injury and improve pneumonia survival.
AB - BACKGROUND: Numerous studies have described the immunosuppressive capacity of
mesenchymal stem cells (MSC) but these studies use mixtures of heterogeneous
progenitor cells for in vitro expansion. Recently, multipotent MSC have been
prospectively identified in murine bone marrow (BM) on the basis of PDFGRa(+)
SCA1(+) CD45(-) TER119(-) (PalphaS) expression but the immunomodulatory capacity
of these MSC is unknown. METHODS: We isolated PalphaS MSC by high-purity FACS
sorting of murine BM and after in vitro expansion we analyzed the in vivo
immunomodulatory activity during acute pneumonia. PalphaS MSC (1 * 10(6)) were
applied intratracheally 4 h after acute respiratory Klebsiella pneumoniae induced
infection. RESULTS: PalphaS MSC treatment resulted in significantly reduced
alveolitis and protein leakage in comparison to mock-treated controls. PalphaS
MSC-treated mice exhibited significantly reduced alveolar TNF-alpha and IL-12p70
expression, while IL-10 expression was unaffected. Dissection of respiratory
dendritic cell (DC) subsets by multiparameter flow cytometry revealed
significantly reduced lung DC infiltration and significantly reduced CD86
costimulatory expression on lung CD103(+) DC in PalphaS MSC-treated mice. In the
post-acute phase of pneumonia, PalphaS MSC-treated animals exhibited
significantly reduced respiratory IL-17(+) CD4(+) T cells and IFN-gamma(+) CD4(+)
T cells. Moreover, PalphaS MSC treatment significantly improved overall pneumonia
survival and did not increase bacterial load. CONCLUSION: In this study we
demonstrated for the first time the feasibility and in vivo immunomodulatory
capacity of prospectively defined MSC in pneumonia.
PMID- 26438076
TI - The anti-aging properties of a human placental hydrolysate combined with dieckol
isolated from Ecklonia cava.
AB - BACKGROUNDS: In the present study, we aimed to examine the anti-aging properties
of human placental hydrolysate (HPE) and dieckol (DE) from Ecklonia cava against
free radical scavenging, muscle hypertrophy-related follistatin mRNA expression,
amelioration of cognition-related genes and proteins, inhibition of collagenase
regulating genes, and elastinase activity. METHODS: The anti-aging effects were
examined in human fibroblast (CCD986sk), mouse myoblast (C2C12), and
neuroblastoma (N2a) cell models, by employing various assays such as 2,2-diphenyl
1-picrylhydrazyl hydrate (DPPH) scavenging, hydroxyl radical-mediated oxidation,
quantitative real-time polymerase chain reaction, enzyme activity, and
immunocytochemistry observation. RESULTS: Our results show that HPE combined with
DE (HPE:DE) strongly scavenged DPPH radicals and protected proteins against
degradation by hydroxyl radical attack. HPE:DE effectively inhibited matrix
metalloproteinase-1 expression, protein kinase C alpha expression, and elastinase
activity. Furthermore, HPE:DE improved the expression of cognition-related genes
(choline acetyltransferase and vesicular acetylcholine transporter). These events
may proactively contribute to retard the aging processes and the abrupt
physiological changes probably induced by mitochondrial dysfunction with aging.
CONCLUSIONS: Based on these findings, we conclude that the combined treatment of
HPE:DE may be useful for anti-aging therapy in which the accumulation of
oxidative damage is the main driving force.
PMID- 26438077
TI - Development of a bead-based Luminex assay using lipopolysaccharide specific
monoclonal antibodies to detect biological threats from Brucella species.
AB - BACKGROUND: Brucella, a Gram-negative bacterium, is classified as a potential
bioterrorism agent mainly due to the low dose needed to cause infection and the
ability to transmit the bacteria via aerosols. Goats/sheep, cattle, pigs, dogs,
sheep and rodents are infected by B. melitensis, B. abortus, B. suis, B. canis,
B. ovis and B. neotomae, respectively, the six classical Brucella species. Most
human cases are caused by B. melitensis and B. abortus. Our aim was to
specifically detect Brucellae with 'smooth' lipopolysaccharide (LPS) using a
highly sensitive monoclonal antibody (mAb) based immunological assay. METHODS: To
complement molecular detection systems for potential bioterror agents, as
required by international biodefense regulations, sets of mAbs were generated by
B cell hybridoma technology and used to develop immunological assays. The
combination of mAbs most suitable for an antigen capture assay format was
identified and an immunoassay using the Luminex xMAP technology was developed.
RESULTS: MAbs specific for the LPS O-antigen of Brucella spp. were generated by
immunising mice with inactivated B. melitensis or B. abortus cells. Most mAbs
recognised both B. melitensis and B. abortus and antigen binding was not impeded
by inactivation of the bacterial cells by gamma irradiation, formalin or heat
treatment, a step required to analyse the samples immunologically under biosafety
level two conditions. The Luminex assay recognised all tested Brucella species
with 'smooth' LPS with detection limits of 2*10(2) to 8*10(4) cells per mL,
depending on the species tested. Milk samples spiked with Brucella spp. cells
were identified successfully using the Luminex assay. In addition, the bead-based
immunoassay was integrated into a multiplex format, allowing for simultaneous,
rapid and specific detection of Brucella spp., Bacillus anthracis, Francisella
tularensis and Yersinia pestis within a single sample. CONCLUSION: Overall, the
robust Luminex assay should allow detection of Brucella spp. in both natural
outbreak and bio-threat situations.
PMID- 26438078
TI - Oral albuterol to treat symptomatic bradycardia in acute spinal cord injury.
PMID- 26438080
TI - Children's implicit recall of junk food, alcohol and gambling sponsorship in
Australian sport.
AB - BACKGROUND: In Australia, sport is saturated by the promotion of junk food,
alcohol and gambling products. This is particularly evident on player jerseys.
The effect of this advertising on children, who are exposed to these messages
while watching sport, has not been thoroughly investigated. The aim of this
research study was to investigate: (1) the extent to which children implicitly
recalled shirt sponsors with the correct sporting team; (2) whether children
associated some types of sponsors with certain sporting codes more than others;
and (3) whether age of the children influenced the correct recall of sponsoring
brands and teams. METHOD: This experimental study conducted in New South Wales,
Australia used projective techniques to measure the implicit recall of team
sponsorship relationships of 85 children aged 5-12 years. Participants were asked
to arrange two sets of magnets - one which contained sporting teams and one which
contained brand logos - in the manner deemed most appropriate by them. Children
were not given any prompts relating to sporting sponsorship relationships.
RESULTS: Three quarters (77 %) of the children were able to identify at least one
correct shirt sponsor. Children associated alcohol and gambling brands more
highly with the more popular sporting code, the National Rugby League compared to
the Australian Football League sporting code. Results showed that age had an
effect on number of shirt sponsors correctly recalled with 9-12 year olds being
significantly more likely than 5-8 year olds to correctly identify team sponsors.
CONCLUSIONS: Given children's ability to implicitly recall shirt sponsors in a
sporting context, Australian sporting codes should examine their current
sponsorship relationships to reduce the number of unhealthy commodity shirt
sponsors. While there is some regulation that protects children from the
marketing of unhealthy commodity products, these findings suggest that children
are still exposed to and recall these sponsorship relationships. Results suggest
that the promotion of unhealthy commodity products during sporting matches is
contributing to increased awareness amongst children of unhealthy commodity
brands. Further investigation is required to examine the extent and impact of
marketing initiatives during televised sporting matches on children.
PMID- 26438079
TI - ABCB1 C3435T polymorphism and the lipid-lowering response in hypercholesterolemic
patients on statins: a meta-analysis.
AB - BACKGROUND: A number of researches have evaluated the association between the
ABCB1 polymorphism and the lipid-lowering response of statins, but the results
have been inconclusive. To examine the lipid-lowering efficacy and safety
associated with the ABCB1 C3435T polymorphism in hypercholesterolemic patients
receiving statin, all available studies were included in this meta-analysis.
METHODS: A systematic search for eligible studies in the Cochrane library
database, Scopus and PubMed was performed. Articles meeting the inclusion
criteria were comprehensively reviewed, and the available data were accumulated
by the meta-analysis. RESULTS: The results indicated that the comparisons of
CC+CT vs. TT were associated with a significant elevation of the serum HDL-C
levels after statin treatment (CC+CT vs. TT: MD, 2.46; 95 % CI, 0.36 to 4.55; P =
0.02), and the ABCB1 C3435T variant in homozygotes was correlated with decreases
in LDL-C (CC vs. TT: MD, 2.29; 95 % CI, 0.37 to 4.20; P = 0.02) as well as TC (CC
vs. TT: MD, 3.05; 95 % CI, 0.58 to 5.53; P = 0.02) in patients treated with
statin. However, we did not observe a significant association in the TG group or
an association between other genetic models serum lipid parameters. In addition,
statin treatment more than 5 months led to a higher risk of muscle toxicity.
CONCLUSIONS: The evidence from the meta-analysis demonstrated that the ABCB1
C3435T polymorphism may represent a pharmacogenomic biomarker for predicting
treatment outcomes in patients on statins and that statin treatment for more than
5 months can increase the risk of myopathy.
PMID- 26438081
TI - Standardization of hernia surgery.
PMID- 26438082
TI - Minimally invasive surgery for congenital diaphragmatic hernia: a meta-analysis.
AB - OBJECTIVES: To compare the safety and efficacy of minimally invasive surgery
(MIS) with traditional open surgical approach for congenital diaphragmatic hernia
(CDH). METHODS: A literature search was performed using the PubMed database,
Embase, and the Cochrane central register of controlled trials using a defined
set of criteria. The outcomes, which include post-operative mortality, incidence
of hernia recurrence, rates of patch use and complications, were analyzed.
RESULTS: We investigated nine studies, which included 507 patients. All studies
were non-randomized historical control trials. The MIS group had a significantly
lower rate of post-operative death with a risk ratio of 0.26 [95% confidence
interval (CI) 0.10-0.68; p = 0.006] but a greater incidence of hernia recurrence
with a risk ratio of 3.42 (95% CI 1.98-5.88; p < 0.00001). Rates of prosthetic
patch use were similar between the two groups. Fewer cases of surgical
complications were found in the MIS group with a risk ratio of 0.66 (95% CI 0.47
0.94; p = 0.02). CONCLUSIONS: MIS for CDH repair is associated with lower post
operative mortality and morbidity compared with traditional open repair. Although
rate of patch use appears to be comparable, the increased risk of CDH recurrence
should not be ignored. The lack of well-controlled prospective trials still
limits strong evaluations of the two surgical techniques.
PMID- 26438085
TI - Challenges, progress, and new directions in stem cell therapies: a new section
launched in Clinical and Translational Medicine.
PMID- 26438084
TI - Analogue peptides for the immunotherapy of human acute myeloid leukemia.
AB - The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in
clinical trials. However, responses are often short-lived and rarely induce
notable memory responses. The reason is that self-antigens have already been
presented to the immune system as the tumor develops, leading to tolerance or
some degree of host tumor cell destruction. To try to break tolerance against
self-antigens, one of the methods employed has been to modify peptides at the
anchor residues to enhance their ability to bind major histocompatibility complex
molecules, extending their exposure to the T-cell receptor. These modified or
analogue peptides have been investigated as stimulators of the immune system in
patients with different cancers with variable but sometimes notable success. In
this review we describe the background and recent developments in the use of
analogue peptides for the immunotherapy of acute myeloid leukemia describing
knowledge useful for the application of analogue peptide treatments for other
malignancies.
PMID- 26438083
TI - Association of Hearing Impairment With Incident Frailty and Falls in Older
Adults.
AB - OBJECTIVE: We aimed to determine whether hearing impairment (HI) in older adults
is associated with the development of frailty and falls. METHOD: Longitudinal
analysis of observational data from the Health, Aging and Body Composition study
of 2,000 participants aged 70 to 79 was conducted. Hearing was defined by the
pure-tone-average of hearing thresholds at 0.5, 1, 2, and 4 kHz in the better
hearing ear. Frailty was defined as a gait speed of <0.60 m/s and/or inability to
rise from a chair without using arms. Falls were assessed annually by self
report. RESULTS: Older adults with moderate-or-greater HI had a 63% increased
risk of developing frailty (adjusted hazard ratio [HR] = 1.63, 95% confidence
interval [CI] = [1.26, 2.12]) compared with normal-hearing individuals. Moderate
or-greater HI was significantly associated with a greater annual percent increase
in odds of falling over time (9.7%, 95% CI = [7.0, 12.4] compared with normal
hearing, 4.4%, 95% CI = [2.6, 6.2]). DISCUSSION: HI is independently associated
with the risk of frailty in older adults and with greater odds of falling over
time.
PMID- 26438086
TI - Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth
factor receptor signaling in Her-2 negative breast cancer cells.
AB - Overexpression and activation of tyrosine kinase receptors like EGFR and Src
regulate the progression and metastasis of Her-2 negative breast cancer. Recently
we have reported the role of cell membrane interaction of phospholipid-binding
protein annexin A2 (AnxA2) and EGFR in regulating cellular signaling in the
activation of angiogenesis, matrix degradation, invasion, and cancer metastasis.
Beta-galactoside-specific animal lectin galectin-3 is an apoptosis inhibitor, and
cell surface-associated extracellular galectin-3 also has a role in cell
migration, cancer progression, and metastasis. Similar expression pattern and
membrane co-localization of these two proteins made us to hypothesize in the
current study that galectin-3 and AnxA2 interaction is critical for Her-2
negative breast cancer progression. By various experimental analyses, we confirm
that glycosylated AnxA2 at the membrane surface interacts with galectin-3. N
linked glycosylation inhibitor tunicamycin treatment convincingly blocked AnxA2
membrane translocation and its association with galectin-3. To analyze whether
this interaction has any functional relevance, we tried to dissociate this
interaction with purified plant lectin from chickpea (Cicer arietinum
agglutinin). This highly specific 30 kDa plant lectin could dissociate AnxA2 from
endogenous lectin galectin-3 interaction at the cell surface. This dissociation
could down-regulate Bcl-2 family proteins, cell proliferation, and migration
simultaneously triggering cell apoptosis. Targeting this interaction of membrane
surface glycoprotein and its animal lectin in Her-2 negative breast cancer may be
of therapeutic value.
PMID- 26438087
TI - Comparative analysis of four disease prediction models of Parkinson's disease.
AB - Parkinson's disease (PD) is a multi-factorial disorder with high-penetrant
mutations accounting for small percentage of PD. Our previous studies
demonstrated individual association of genetic variants in folate, xenobiotic,
and dopamine metabolic pathways with PD risk. The rational of the study was to
develop a risk prediction model for PD using these genetic polymorphisms along
with synuclein (SNCA) polymorphism. We have generated additive, multifactor
dimensionality reduction (MDR), recursive partitioning (RP), and artificial
neural network (ANN) models using 21 SNPs as inputs and disease outcome as
output. The clinical utility of all these models was assessed by plotting
receiver operating characteristics curves where in area under the curve (AUC) was
used as an index of diagnostic utility of the model. The additive model was the
simplest and exhibited an AUC of 0.72. The MDR model showed significant gene-gene
interactions between SNCA, DRD4VNTR, and DRD2A polymorphisms. The RP model showed
SHMT C1420T as important determinant of PD risk. This variant allele was found to
be protective and this protection was nullified by MTRR A66G. Inheritance of SHMT
wild allele and SNCA intronic polymorphism was shown to increase the risk of PD.
The ANN model showed higher diagnostic utility (AUC = 0.86) compared to all the
models and was able to explain 56.6% cases of sporadic PD. To conclude, the ANN
model developed using SNPs in folate, xenobiotic, and dopamine pathways along
with SNCA has higher clinical utility in predicting PD risk compared to other
models.
PMID- 26438088
TI - Percutaneous dilatational tracheostomy (PDT) in trauma patients: a safe
procedure.
AB - PURPOSE: Percutaneous dilatational tracheostomy (PDT) is a standard procedure
routinely performed on intensive care units. While complication rates and long
term outcomes have been studied in different patient populations, there are few
studies known to these authors involving PDT in trauma patients and the
complications which may result. METHODS: Between March 2007 and August 2013, all
instances and peri-procedural complications during PDT occurring on the trauma
intensive care unit, a unit specialized in the care of injured patients and
especially polytrauma patients, were documented. PDTs were performed by a surgeon
with the assistance and supervision of another, using bronchoscopic guidance
performed by the respiratory medicine department. RESULTS: 289 patients were
included in the study, 225 men and 64 women with a mean age of 49 +/- 21 years.
Complications occurred in 37.4 % of cases. The most common complication,
bleeding, occurred in 26.3 % of patients ranging from little to severe bleeding.
Fracture of tracheal cartilage occurred in 6 % of PDT cases. Additional
complications such as dislocation of the guidewire, hypotension, and oxygen
desaturation were observed. Most complications did not require treatment. The
second tracheal intercartilaginous space was successfully intubated in 82 % of
cases. CONCLUSIONS: PDT is a safe procedure in trauma patients. When considering
the severity of complications such as major blood loss, pneumothorax, or death,
this evidence suggests that PDT is safer in trauma patients compared to other
patient cohorts.
PMID- 26438089
TI - Twenty years of experience with perineal injury in children.
AB - PURPOSE: The aim of this study was to review our 20 years of experience
determining the common mechanisms of perineal trauma and initial management to
evaluate the effects of classification for treatment. METHODS: A total of 75
children with perineal injuries were reviewed retrospectively, including patient
demographics, mechanism of injury, associated injuries, injury severity score,
presenting symptoms and methods of diagnosis and treatment. RESULTS: Amongst the
75 children (55 females and 20 males; mean age, 8 years), fall from height,
followed by motor vehicle crash and sexual abuse were the most common reasons for
injury. The most common symptom on presentation was bleeding, followed by
abdominopelvic pain and tenderness. Eleven patients were allowed to heal
secondarily, and 64 were examined under general anaesthesia. The affected area
was repaired in 48, further diagnostic tools were needed in 20 and 11
cystoscopic, 10 rectoscopic, and 5 vaginoscopic evaluations were performed. Six
patients with full-thickness injuries that extended to the peritoneum were
treated with colostomy, and all were victims of motor vehicle crashes.
CONCLUSION: The genital injury score is a useful genital trauma scale for
predicting anogenital injury severity. Identifying the mechanism and severity of
perineal and associated injuries under general anaesthesia may facilitate
appropriate classification and management.
PMID- 26438090
TI - [Ultrasound elastography].
AB - Noninvasive, ultrasound-based methods for visualizing and measuring tissue
elasticity are becoming more and more common in routine practice. Using hepatic
shear wave elastography, cut-off levels can help to detect the degree of relevant
fibrosis (F >= 2) with a diagnostic accuracy using the area under the reader
operating characteristic (AUROC) of 87 % and cirrhosis (F = 4, AUROC 93 %).
Normal values virtually exclude liver cirrhosis (negative predictive value up to
97 %) and high shear wave velocities predict complications in the course of
primary sclerosing cholangitis, liver cirrhosis and chronic hepatitis B or C.
Elastography is of no relevant help in the differentiation of the dignity of
hepatic lesions. Concerning thyroid or breast lesions, low shear wave velocities
are indicative of benign lesions and in contrast, high velocities of malignant
lesions. A differentiation between benign and malignant thyroid nodules is
performed by elastography with a sensitivity of 89 % and a specificity of 82 %.
In breast lesions a differentiation of nodes can be improved with elastography
compared to B-mode ultrasound alone with a sensitivity of 97 % and a specificity
of 83 %. Invasive biopsy punctures can therefore be specifically performed or can
be omitted. Due to several influencing factors, in particular during liver
elastography, the measurements need to be interpreted in the clinical context. In
summary, ultrasound-based elastography provides helpful information for the
detection of hepatic fibrosis and for further characterization of thyroid or
breast lesions in addition to classical techniques, such as B-mode imaging and
color Doppler.
PMID- 26438091
TI - [Optoacoustic imaging].
AB - CLINICAL/METHODICAL ISSUE: Imaging modalities play an increasing role in today's
medical diagnostics. Among them, ultrasound (US) is one the most widespread
techniques although it has relatively poor soft tissue contrast. Furthermore, US
is poorly suited as a modality for molecular imaging (MI). STANDARD RADIOLOGICAL
METHODS: Methods such as Doppler and contrast-enhanced US (CEUS) allow functional
imaging of the vasculature; however, ultrasound-based MI remains limited to the
vascular network due to the size of available contrast agents. METHODICAL
INNOVATIONS: Optoacoustic imaging combines the benefits of optics (high contrast)
with those of acoustics (low scattering and high resolution). In this technique,
signals are generated in tissue with high contrast depending on the local optical
absorption coefficient and detected with an acoustic procedure. PERFORMANCE:
Optoacoustic imaging can intrinsically be scaled in terms of resolution and is
therefore usable in various applications from in vitro microscopy, to preclinical
small animal imaging up to clinical imaging. With a resolution in the range of
clinical ultrasound systems (100-400 um), highly scattering tissue can be imaged
up to several centimeters in depth. ACHIEVEMENTS: In contrast to conventional
ultrasound imaging, optoacoustic techniques are highly suitable for MI. Various
contrast agents as well as different technical implementations of the approach
have already been preclinically evaluated. The technique is currently close to
being transferred to clinical implementation and the first studies have already
been started. PRACTICAL RECOMMENDATIONS: Clinical studies are ongoing with
respect to early diagnosis of breast cancer and arthritis. Furthermore, the
suitability of the technique for skin imaging is currently being investigated.
PMID- 26438092
TI - [Transcranial focused ultrasound: Neurological applications of magnetic resonance
guided high-intensity focused ultrasound].
AB - BACKGROUND: Ultrasound surgery uses the thermal effects of the absorption of high
intensity focused ultrasound to induce localized thermal ablation of diseased
tissue. The clinical introduction in recent years was made possible by a better
understanding of the interactions of ultrasound with biological structures and
the resulting physiological changes, major advances in the design of ultrasound
applicators and the development of imaging modalities for reliable guiding the
interventions. METHODS: Magnetic resonance imaging-guided focused ultrasound
surgery (MRgFUS) is especially appealing for applications in the brain where
target volumes have to be accessed with high precision without inflicting
collateral damage to surrounding healthy tissue. In 2013 a MRgFUS system was CE
certified for the treatment of functional neurological disorders, such as chronic
neuropathic pain and movement disorders. Currently, some 400 patients have been
treated worldwide using this system, which is also undergoing clinical testing
for the treatment of primary brain tumors and brain metastases. CONCLUSION: This
article describes the technical basis of transcranial focused ultrasound
neurosurgery and summarizes the current clinical experience of this new class of
image-guided, non-invasive interventions.
PMID- 26438093
TI - [Ultrasound motion tracking for radiation therapy].
AB - BACKGROUND: In modern radiotherapy the radiation dose can be applied with an
accuracy in the range of 1-2 mm provided that the exact position of the target is
known. If, however, the target (the tumor) is located in the lungs or the
abdomen, respiration or peristalsis can cause substantial movement of the target.
METHODS: Various methods for intrafractional motion detection and compensation
are currently under consideration or are already applied in clinical practice.
Sonography is one promising option, which is now on the brink of clinical
implementation. Ultrasound is particularly suited for this purpose due to the
high soft tissue contrast, real-time capability, the absence of ionizing
radiation and low acquisition costs. Ultrasound motion tracking is an image-based
approach, i.e. the target volume or an adjacent structure is directly monitored
and the motion is tracked automatically on the ultrasound image. Diverse
algorithms are presently available that provide the real-time target coordinates
from 2D as well as 3D images. Definition of a suitable sonographic window is not,
however, trivial and a gold standard for positioning and mounting of the
transducer has not yet been developed. Furthermore, processing of the coordinate
information in the therapy unit and the dynamic adaptation of the radiation field
are challenging tasks. CONCLUSION: It is not clear whether ultrasound motion
tracking will become established in the clinical routine although all technical
prerequisites can be considered as fulfilled, such that exciting progress in this
field of research is still to be expected.
PMID- 26438094
TI - [Molecular ultrasound imaging: Clinical applications].
AB - BACKGROUND: Contrast-enhanced ultrasound imaging is increasingly being used in
clinical applications, particularly for cardiovascular and liver diagnostics. In
this context the availability of new molecular contrast agents and the initiation
of clinical translation promises new options for pathomechanistic diagnostics.
MATERIAL AND METHODS: Analysis of the current literature on the development of
molecular ultrasound contrast agents, the detection methods as well as the
applications in preclinical and clinical studies. RESULTS: Molecular contrast
agents have become established in preclinical research for the detection of
inflammation and angiogenesis and have been continuously refined over recent
years. They consist of gas filled microbubbles with a diameter of 1-5 um and the
gas core is stabilized by a shell made of lipids, proteins or polymers to which
biomolecules are conjugated that determine the target specificity. The agent BR55
is the first clinically evaluated molecular ultrasound contrast agent. It binds
to the angiogenesis marker vascular endothelial growth factor receptor 2 (VEGFR2)
and has been studied in several preclinical and clinical phase I and II studies
on tumor diagnostics and characterization. CONCLUSION: Molecular ultrasound
imaging is rapidly evolving in preclinical research for a broad field of
applications. Translation to clinical practice is conceivable for many
indications and is already ongoing for BR55.
PMID- 26438095
TI - Cerebellum-inspired neural network solution of the inverse kinematics problem.
AB - The demand today for more complex robots that have manipulators with higher
degrees of freedom is increasing because of technological advances. Obtaining the
precise movement for a desired trajectory or a sequence of arm and positions
requires the computation of the inverse kinematic (IK) function, which is a major
problem in robotics. The solution of the IK problem leads robots to the precise
position and orientation of their end-effector. We developed a bioinspired
solution comparable with the cerebellar anatomy and function to solve the said
problem. The proposed model is stable under all conditions merely by parameter
determination, in contrast to recursive model-based solutions, which remain
stable only under certain conditions. We modified the proposed model for the
simple two-segmented arm to prove the feasibility of the model under a basic
condition. A fuzzy neural network through its learning method was used to compute
the parameters of the system. Simulation results show the practical feasibility
and efficiency of the proposed model in robotics. The main advantage of the
proposed model is its generalizability and potential use in any robot.
PMID- 26438096
TI - Real-time aortic pulse wave velocity measurement during exercise stress testing.
AB - BACKGROUND: Pulse wave velocity (PWV), a measure of arterial stiffness, has been
demonstrated to be an independent predictor of adverse cardiovascular outcomes.
This can be derived non-invasively using cardiovascular magnetic resonance (CMR).
Changes in PWV during exercise may reveal further information on vascular
pathology. However, most known CMR methods for quantifying PWV are currently
unsuitable for exercise stress testing. METHODS: A velocity-sensitive real-time
acquisition and evaluation (RACE) pulse sequence was adapted to provide
interleaved acquisition of two locations in the descending aorta (at the level of
the pulmonary artery bifurcation and above the renal arteries) at 7.8 ms temporal
resolution. An automated method was used to calculate the foot-to-foot transit
time of the velocity pulse wave. The RACE method was validated against a standard
gated phase contrast (STD) method in flexible tube phantoms using a pulsatile
flow pump. The method was applied in 50 healthy volunteers (28 males) aged 22-75
years using a MR-compatible cycle ergometer to achieve moderate work rate (38 +/-
22 W, with a 31 +/- 12 bpm increase in heart rate) in the supine position.
Central pulse pressures were estimated using a MR-compatible brachial device.
Scan-rescan reproducibility was evaluated in nine volunteers. RESULTS: Phantom
PWV was 22 m/s (STD) vs. 26 +/- 5 m/s (RACE) for a butyl rubber tube, and 5.5 vs.
6.1 +/- 0.3 m/s for a latex rubber tube. In healthy volunteers PWV increased with
age at both rest (R(2) = 0.31 p < 0.001) and exercise (R(2) = 0.40, p < 0.001).
PWV was significantly increased at exercise relative to rest (0.71 +/- 2.2 m/s, p
= 0.04). Scan-rescan reproducibility at rest was -0.21 +/- 0.68 m/s (n = 9).
CONCLUSIONS: This study demonstrates the validity of CMR in the evaluation of PWV
during exercise in healthy subjects. The results support the feasibility of using
this method in evaluating of patients with systemic aortic disease.
PMID- 26438097
TI - Butylidenephthalide antagonizes cromakalim-induced systolic pressure reduction in
conscious normotensive rats.
AB - BACKGROUND: Butylidenephthalide (Bdph), a main constituent of Ligusticum
chuanxiong Hort., was reported to have selective antianginal effect without
changing blood pressure in conscious rat. Recently, we have observed that Bdph
antagonized cromakalim, an ATP-dependent K(+) channel opener, in guinea-pig
trachea. Thus, we were interested in investigating whether Bdph at the dose
without changing blood pressure antagonized cromakalim-induced systolic pressure
reduction in conscious rats. METHODS: Systolic arterial pressures of conscious
rats were determined by using the indirect tail-cuff method. RESULTS: Bdph (30
mg/kg, i.p.) did not affect baseline systolic pressure in conscious normotensive
and spontaneous hypertensive rats. Bdph (30 mg/kg, i.p.) also did not affect log
dose-response curves of prazosin, clonidine and Bay K 8644, a Ca(2+) channel
activator, in normotensive rats. However, Bdph (30 mg/kg, i.p.) similar to 4
aminopyridine (4-AP, 0.4 mg/kg, i.p.), a K(+) channel blocker, non-parallelly but
surmountably, and partially similar to glibenclamide (GBC, 10 mg/kg, i.v.), an
ATP-sensitive K(+) channel blocker, surmountably but not parallelly rightward
shifted the log dose-systolic pressure reduction curve of cromakalim, an ATP
sensitive K(+) channel opener, in normotensive rats, respectively. DISCUSSION:
The antagonistic effect of Bdph against cromakalim was similar to that of 4-AP, a
K+ channel blocker of Kv1 family, and partially similar to that of GBC, an ATP
sensitive K+ channel blocker. Thus, Bdph may be a kind of K+ channel blockers,
which have been reviewed to have a potential clinical use for Alzheimer disease.
Indeed, Bdph has also been reported to reverse the deficits of inhibitory
avoidance performance and improve memory in rats. Recently, 4-AP was reported to
treat Episodic ataxia type 2 (EA2) which is a form of hereditary neurological
disorder. Consistently, Bdph was recently reported to have antihyperglycemic
activity in mice, since GBC is a powerful oral hypoglycemic drug. CONCLUSIONS:
Bdph similar to 4-AP and partially similar to GBC may block Kv1 family and ATP
sensitive K(+) channels in conscious normotensive rats.
PMID- 26438098
TI - Discovery of a Novel Linoleate Dioxygenase of Fusarium oxysporum and Linoleate
Diol Synthase of Colletotrichum graminicola.
AB - Fungal pathogens constitute serious threats for many forms of life. The
pathogenic fungi Fusarium and Colletotrichum and their formae speciales (f. spp.)
infect many types of crops with severe consequences and Fusarium oxysporum can
also induce keratitis and allergic conditions in humans. These fungi code for
homologues of dioxygenase-cytochrome P450 (DOX-CYP) fusion proteins of the animal
heme peroxidase (cyclooxygenase) superfamily. The objective was to characterize
the enzymatic activities of the DOX-CYP homologue of Colletotrichum graminicola
(EFQ34869) and the DOX homologue of F. oxysporum (EGU79548). The former oxidized
oleic and linoleic acids in analogy with 7,8-linoleate diol synthases (LDSs), but
with the additional biosynthesis of 8,11-dihydroxylinoleic acid. The latter
metabolized fatty acids to hydroperoxides with broad substrate specificity. It
oxidized 20:4n-6 and 18:2n-6 to hydroperoxides with an R configuration at the (n
10) positions, and other n-6 fatty acids in the same way. [11S-(2)H]18:2n-6 was
oxidized with retention and [11R-(2)H]18:2n-6 with loss of deuterium, suggesting
suprafacial hydrogen abstraction and oxygen insertion. Fatty acids of the n-3
series were oxidized less efficiently and often to hydroperoxides with an R
configuration at both (n-10) and (n-7) positions. The enzyme spans 1426 amino
acids with about 825 residues in the N-terminal domain with DOX homology and 600
residues at the C-terminal domain without homology to other enzymes. We conclude
that fungal oxylipins can be formed by two novel subfamilies of cyclooxygenase
related DOX.
PMID- 26438099
TI - Involvement of Subcortical Brain Structures During Olfactory Stimulation in
Multiple Chemical Sensitivity.
AB - Multiple chemical sensitivity (MCS) patients usually react to odour compounds and
the majority of neuroimaging studies assessed, especially at the cortical level,
many olfactory-related correlates. The purpose of the present study was to depict
sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory
stimulation by using a recently validated (18)F-2-fluoro-2-deoxy-D-glucose (FDG)
positron emission tomography/computer tomography procedure in 26 MCS and 11
healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve
subcortical volumes of interest were identified by the automated anatomical
labeling library and normalized to thalamus FDG uptake. In both groups, when
comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased
metabolism in bilateral putamen and hippocampus and a relative increased
metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum.
The between-groups ANOVA demonstrated in MCS a significant higher metabolism in
bilateral OLF during NC. As in HC subjects negative correlations were found in OC
between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness
scale, the latter positively correlated with MCS subjects' bilateral putamen FDG
uptake in OC. Besides FDG uptake resemblances in both groups were found, for the
first time a relative higher metabolism increase in OLF in MCS subjects at rest
with respect to HC was found. When merging this aspect to the different
subcortical FDG uptake correlations patterns in the two groups, the present study
demonstrated to describe a peculiar metabolic index of behavioral and
neurological aspects of MCS complaints.
PMID- 26438100
TI - Brachial artery endothelial function is stable across the morning in young men.
AB - BACKGROUND: The morning hours are associated with increased cardiovascular (CV)
risk, and vascular endothelial function (VEF) is a strong predictor of CV
disease. A diurnal rhythm in VEF has been established but the morning variation
in VEF is not well-documented. Thus, we tested if VEF is impaired across the
vulnerable morning period. METHODS: After overnight fasts, eight healthy men (age
26.3 +/- 3 yr) underwent assessments of VEF under standardized testing conditions
every 2 h from 0700 to 1300 h on two separate days. VEF was estimated following 5
min brachial artery occlusions by hyperemic flow-mediated dilation (FMD).
RESULTS: There was no significant change in FMD or hyperemic shear stimulus
across the 6 h vulnerable period on either day, despite changes in physical
activity and meals across these periods. CONCLUSION: In this healthy group of
young men, VEF is stable across the vulnerable morning period when typical
behaviors occurred (breakfast and physical activity). Future research should
focus on the roles of sleep, physical inactivity during sleep and endogenous
circadian rhythm in VEF.
PMID- 26438102
TI - Acute dyspnea caused by a giant spindle cell lipoma of the larynx.
AB - BACKGROUND: The spindle cell lipoma (SCL) is a special type of lipoma and this is
very rare in the head and neck regions. There are only five reported cases exist,
which describes the occurrence of a SCL in the hypopharynx. METHODS: Our case
report presents a case of a very large SCL in the larynx. We want to describe
that how we treated the patients and compared the situation with other reported
cases. RESULTS: Intraoperatively, we found a tumor mass of 7 * 5 cm. It was
successfully removed with the carbon dioxide laser. No postoperative
complications occurred. CONCLUSIONS: Although SCL is a very rare diagnosis in the
larynx/hypopharynx, it should be included in the differential diagnosis of
larynx/hypopharynx tumors. Our case is the first report of such a large SCL in
the larynx. The clinical symptoms occurred relatively late and ended up in an
acute situation of stridor and dyspnea.
PMID- 26438101
TI - Influence of adult role modeling on child/adolescent helmet use in recreational
sledging: an observational study.
AB - BACKGROUND: During recreational sledging (tobogganing), the head represents the
most frequent injured body region with approximately one-third of all sledging
injuries among children and adolescents. Whether children are wearing a helmet or
not might be influenced on parental encouragement and role modeling of helmet
use. Therefore, the aim of this study was to evaluate the impact of adult helmet
use on child/adolescent helmet use in recreational sledging. METHODS: More than
500 adults sitting together with another adult or child/adolescent on a two
seater sledge were interviewed during two winter seasons at the bottom of six
sledging tracks on demographics, mean frequency of sledging per season, self
estimated skill level, risk-taking behavior, and the use of a helmet. RESULTS:
Total helmet use of all observed persons was 41.0 %. Helmet use among interviewed
adults significantly increased with increasing age up to 45 years, frequency of
sledging, and skill level, respectively. Helmet use of interviewed adults was
46.5 % if a child/adolescent was sitting on the same sledge and 29.8 % (odds
ratios (OR): 2.1, 95 % confidence intervals (CI): 1.4-2.9, p < 0.001) when
sledging together with another adult. Helmet use was 71.3 % among
children/adolescents and 26.7 % among adults (OR: 6.8, 95 % CI: 4.6-10.1, p <
0.001) sitting on the same sledge as the interviewed person, respectively.
CONCLUSION: Adults were wearing more often a helmet during recreational sledging
when sitting together with a child/adolescent on the sledge. However, helmet use
during sledging is clearly below 50 %. Thus, more intense educational campaigns
on helmet use are urgently needed for tobogganists.
PMID- 26438103
TI - Assessment of smoking for low bone mineral density in postmenopausal Turkish
women.
AB - OBJECTIVE: To investigate the effect of cigarette smoking on bone mineral density
(BMD) in postmenopausal Turkish women. STUDY DESIGN: A total of 175
postmenopausal Turkish women admitted to Tepecik Training and Research Hospital
for a routine menopausal checkup were included in this study. All participants
completed a questionnaire regarding their age, educational status, parity, number
of abortus, time since menopause, caffeine intake, tobacco use, alcohol
consumption, history of a previous fracture related to trauma, and taking any
medication for menopause and osteoporosis. Of all subjects, 23.3% (n = 39) were
smokers and 77.7% (n = 136) were nonsmokers. T-scores and Z-scores of vertebra
and femur neck were assessed using dual energy X-ray absorptiometry (DXA). For
analyzing the results, Student t-test, one-way ANOVA, Mann-Whitney U test,
Pearson correlation, and Kruskal-Wallis test were performed. RESULTS: Femur T
scores (- 0.78 +/- 1.07 vs. - 0.32 +/- 1.56) and vertebra T-scores (- 2.26 +/-
1.23 vs. - 1.82 +/- 1.04) were significantly lower in smoking women than
nonsmoking women (p < 0.05). However, there were no significant difference
between duration of smoking, number of cigarettes consumed per day, and BMD (p >
0.05) CONCLUSION: Cigarette smoking is one of the modifiable risk factors
influencing bone density in postmenopausal Turkish women. "Cessation of
cigarette" should be recommended for lifestyle modifications to prevent
postmenopausal osteoporosis.
PMID- 26438104
TI - Characterising atypical Candida albicans clinical isolates from six third-level
hospitals in Bogota, Colombia.
AB - BACKGROUND: Candida species are the most frequently found fungal pathogens
causing nosocomial disease in a hospital setting. Such species must be correctly
identified to ensure that appropriate control measures are taken and that
suitable treatment is given for each species. Candida albicans is causing most
fungal disease burden worldwide; the challenge lies in differentiating it from
emerging atypical, minor and related species such as Candida dubliniensis and
Candida africana. The purpose of this study was to compare identification based
on MALDI-TOF MS to standard identification systems using a set of nosocomial
isolates. METHODS: Eleven nosocomial samples were collected from 6 third-level
hospitals in Bogota, Colombia. All the samples were identified by combining MALDI
TOF MS with morphological characters, carbohydrate assimilation and molecular
markers (D1/D2 and HWP1). RESULTS: The present work describes the first
collection of atypical Colombian Candida clinical isolates; these were identified
as Candida albicans/Candida africana by their MALDI-TOF MS profile. Phenotypical
characteristics showed that they were unable to produce chlamydospores,
assimilate trehalose, glucosamine, N- acetyl-glucosamine and barely grew at 42
degrees C, as would be expected for Candida africana. The molecular
identification of the D1/D2 region of large subunit ribosomal RNA and HWP1 hyphal
cell wall protein 1 sequences from these isolates was consistent with those for
Candida albicans. The mass spectra obtained by MALDI-TOF MS were analysed by
multi-dimensional scaling (MDS) and cluster analysis, differences being revealed
between Candida albicans, Candida africana, Candida dubliniensis reference
spectra and two clinical isolate groups which clustered according to the clinical
setting, one of them being clearly related to C. albicans. CONCLUSION: This study
highlights the importance of using MALDI-TOF MS in combination with morphology,
substrate assimilation and molecular markers for characterising Candida albicans
related and atypical C. albicans species, thereby overcoming conventional
identification methods. This is the first report of hospital-obtained isolates of
this type in Colombia; the approach followed might be useful for gathering
knowledge regarding local epidemiology which could, in turn, have an impact on
clinical management. The findings highlight the complexity of distinguishing
between typical and atypical Candida albicans isolates in hospitals.
PMID- 26438105
TI - A de novo microdeletion in NRXN1 in a Dutch patient with mild intellectual
disability, microcephaly and gonadal dysgenesis.
AB - This report is regarding a Dutch female with microcephaly, mild intellectual
disability (ID), gonadal dysgenesis and dysmorphic facial features with
synophrys. Upon genotyping, an ~455 kb de novo deletion encompassing the first
exon of NRXN1 was found. Bidirectional sequencing of the coding exons of the
NRXN1 alpha isoform was subsequently performed to investigate the possibility of
a pathogenic mutation on the other allele, but we could not find any other
mutation. Previously, many heterozygous mutations as well as microdeletions in
NRXN1 were shown to be associated with ID, autism, schizophrenia, and other
psychiatric and psychotic disorders. Our results are in agreement with other
reports that show that NRXN1 deletions can lead to ID, microcephaly and mild
dysmorphic features. However, this is the first report of gonadal dysgenesis
being associated with such deletions. It is not clear whether there is a causal
relationship between the NRXN1 deletion and gonadal dysgenesis, but it is of
interest that the FSHR gene, which encodes the follicle-stimulating hormone
receptor causative correlation that is mutated in ovarian dysgenesis, is located
proximal to the NRXN1 gene. Given that most of the females carrying NRXN1
deletions have been diagnosed at a prepubertal age, gynecologic screening of
female carriers of a NRXN1 deletion is warranted.
PMID- 26438106
TI - Erratum to: Early Glycemic Response Predicts Achievement of Subsequent Treatment
Targets in the Treatment of Type 2 Diabetes: A Post hoc Analysis.
PMID- 26438107
TI - Characterization of Sitagliptin Use in Patients with Type 2 Diabetes and Chronic
Kidney Disease by Cross-Sectional Analysis of a Medical Insurance Claims
Database.
AB - INTRODUCTION: Chronic kidney disease (CKD) is common in patients with type 2
diabetes (T2DM) and makes them particularly susceptible to safety/tolerability
issues related to many classes of oral antihyperglycemic agents (OAHA).
Dipeptidyl peptidase-4 inhibitors (DPP-4is) like sitagliptin are generally well
tolerated in patients with T2DM and renal disease and therefore may be
preferentially used in patients with CKD. To assess the extent of this
preference, the characteristics of sitagliptin users with T2DM and CKD were
compared with those of other (non-DPP-4i) OAHA users with T2DM and CKD. METHODS:
Patients with T2DM and CKD with claims between 2006 and 2012 were identified from
a United States insurance claims database. Patients starting sitagliptin or
another OAHA as mono, dual, or triple therapy were compared. Demographic and
clinical characteristics within 5 years before starting or escalating to new
therapies were assessed. RESULTS: Compared to patients with CKD starting other
OAHAs, patients with CKD starting sitagliptin as mono or dual therapy were older,
had more physician visits, were more likely to have a history of heart failure
and to use loop diuretics. In triple therapy patients, the differences between
groups were not as pronounced, but the overall prevalences of comorbidities was
higher. CONCLUSION: Similar to prior observations in a general T2DM population,
patients with T2DM and CKD prescribed sitagliptin tend to be older and have more
comorbidities than those prescribed other classes of OAHA. If not recognized and
analyzed appropriately, this channeling could lead to biased treatment effect
estimates in comparative analyses that include users of sitagliptin. FUNDING:
Merck & Co., Inc., Kenilworth, NJ, USA.
PMID- 26438108
TI - Repetitive Transcranial Magnetic Stimulation (rTMS) for the cognitive
rehabilitation of traumatic brain injury (TBI) victims: study protocol for a
randomized controlled trial.
AB - BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) has been proposed
as a new tool in neurological rehabilitation of victims of traumatic brain injury
(TBI). However, its usefulness to treat this condition has never been tested
rigorously. The primary goal is to conduct a study protocol to determine whether
rTMS used to cognitive rehabilitation of victims of TBI with diffuse axonal
injury (DAI) is a safe instrument and if it enhances cognitive function recovery.
METHODS: Double-blind randomized controlled trial of patients with diffuse axonal
injury. Thirty-six patients will be randomized to either an active coil group or
sham group in a 1:1 ratio. rTMS protocol: 10 sessions of high-frequency rTMS (10
Hz) over the left dorsolateral prefrontal cortex (DLPFC). Cortical Excitability
measures will be obtained. Neuropsychological evaluations will be performed 1
week before, 1 week and 3 months after rTMS. There are 2 study hypotheses: (1)
rTMS over the left DLPFC in patients with DAI will improve cognitive function and
(2) whether rTMS is safe in TBI patients. DISCUSSION: This study evaluates the
immediate and delayed effects of rTMS over the DLPFC on the cognitive domain of
patients with DAI following TBI. rTMS has shown good results in treating major
depression and may be promising for patients with TBI. As such, the results of
this study can greatly modify the cognitive rehabilitation strategies. TRIAL
REGISTRATION: This trial was registered in clinicaltrials.gov ( NCT02167971 ) on
17 June 2014.
PMID- 26438109
TI - Prevalence and factors associated with musculoskeletal disorders and rheumatic
diseases in indigenous Maya-Yucateco people: a cross-sectional community-based
study.
AB - This study aimed to estimate the prevalence of musculoskeletal disorders and
rheumatic diseases in indigenous Maya-Yucateco communities using Community
Oriented Program for Control of Rheumatic Diseases (COPCORD) methodology. The
study population comprised subjects aged >=18 years from 11 communities in the
municipality of Chankom, Yucatan. An analytical cross-sectional study was
performed, and a census was used. Subjects positive for musculoskeletal (MSK)
pain were examined by trained physicians. A total of 1523 community members were
interviewed. The mean age was 45.2 years (standard deviation (SD) 17.9), and 917
(60.2 %) were women. Overall, 592 individuals (38.8 %; 95 % CI 36.3-41.3 %) had
experienced MSK pain in the last 7 days. The pain intensity was reported as
"strong" to "severe" in 43.4 %. The diagnoses were rheumatic regional pain
syndromes in 165 (10.8 %; 95 % CI 9.4-12.5), low back pain in 153 (10.0 %; 95 %
CI 8.5-11.6), osteoarthritis in 144 (9.4 %; 95 % CI 8.0-11.0), fibromyalgia in 35
(2.2 %; 95 % CI 1.6-3.1), rheumatoid arthritis in 17 (1.1 %; 95 % CI 0.6-1.7),
undifferentiated arthritis in 8 (0.5 %; 95 % CI 0.2-0.8), and gout in 1 (0.06 %;
95 % CI 0.001-0.3). Older age, being female, disability, and physically demanding
work were associated with a greater likelihood of having a rheumatic disease. In
conclusion, MSK pain and rheumatic diseases were highly prevalent. The high
impact of rheumatic diseases on daily activities in this indigenous population
suggests the need to organize culturally-sensitive community interventions for
the prevention of disabilities caused by MSK disorders and diseases.
PMID- 26438110
TI - Genetic analysis of enteropathogenic Escherichia coli (EPEC) adherence factor
(EAF) plasmid reveals a new deletion within the EAF probe sequence among O119
typical EPEC strains.
AB - BACKGROUND: Enteropathogenic Escherichia coli (EPEC) are classified into typical
and atypical strains based on the presence of the E. coli adherence factor (EAF)
plasmid. The EAF plasmid contains the bfp (bundle-forming pilus) operon and the
perABC (plasmid encoded regulator) gene cluster. A 1-kb cryptic region of EAF
plasmid has been widely used as a genetic probe for EPEC detection. However, some
EPEC strains may harbor an EAF plasmid lacking the EAF probe sequence, which
makes the differentiation between typical and atypical a complex task. In this
study, we report the genetic analysis of the EAF plasmid-encoded genes in a
collection of EPEC clinical isolates. METHODS: A total of 222 EPEC clinical
isolates, which were previously classified as typical (n=70) or atypical (n=152)
by EAF probe reactivity, were screened for the presence of different EAF
sequences by PCR and DNA hybridization. RESULTS: All typical strains possessed
intact bfpA and perA genes, and most of them were positive in the PCR for EAF
probe sequence. However, a subset of 30 typical strains, 22 of which belonged to
O119 serogroup, presented a 1652 pb deletion in the region between 1093-bp
downstream perC and 616-bp of the EAF fragment. The bfpA, bfpG, and per genes
were found in all typical strains. In addition, 32 (21%) atypical strains
presented the perA gene, and 20 (13.2%) also presented the bfpA gene. Among the
32 strains, 16 belonged to the O119:H2, O119:HND, and ONT:HND serotypes. All 32
atypical strains contained perA mutation frameshifts and possessed an IS1294
element upstream of the per operon as detected by PCR followed by restriction
fragment length polymorphism (RFLP) typing and multiplex PCR. Among the 20 bfpA
probe-positive strains, eight O119 strains possessed deletion in the bfp operon
at the 3'end of bfpA due to an IS66 element. CONCLUSION: Our data show that
typical O119 strains may contain a deletion within the EAF probe sequence not
previously reported. This new finding suggests that care should be taken when
using the previously described EAF PCR assay in epidemiological studies for the
detection of typical O119 strains. In addition, we were able to confirm that some
atypical strains carry vestiges of the EAF plasmid.
PMID- 26438111
TI - Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict
Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy:
American Society of Clinical Oncology Provisional Clinical Opinion Update 2015.
AB - PURPOSE: An American Society of Clinical Oncology Provisional Clinical Opinion
(PCO) offers timely clinical direction after publication or presentation of
potentially practice-changing data from major studies. This PCO update addresses
the utility of extended RAS gene mutation testing in patients with metastatic
colorectal cancer (mCRC) to detect resistance to anti-epidermal growth factor
receptor (EGFR) monoclonal antibody (MoAb) therapy. CLINICAL CONTEXT: Recent
results from phase II and III clinical trials in mCRC demonstrate that patients
whose tumors harbor RAS mutations in exons 2 (codons 12 and 13), 3 (codons 59 and
61), and 4 (codons 117 and 146) are unlikely to benefit from therapy with MoAbs
directed against EGFR, when used as monotherapy or combined with chemotherapy.
RECENT DATA: In addition to the evidence reviewed in the original PCO, 11
systematic reviews with meta-analyses, two retrospective analyses, and two health
technology assessments based on a systematic review were obtained. These
evaluated the outcomes for patients with mCRC with no mutation detected or
presence of mutation in additional exons in KRAS and NRAS. PCO: All patients with
mCRC who are candidates for anti-EGFR antibody therapy should have their tumor
tested in a Clinical Laboratory Improvement Amendments-certified laboratory for
mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61),
and 4 (codons 117 and 146). The weight of current evidence indicates that anti
EGFR MoAb therapy should only be considered for treatment of patients whose tumor
is determined to not have mutations detected after such extended RAS testing.
PMID- 26438112
TI - Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors As Adjuvant Therapy
in Completely Resected Non-Small-Cell Lung Cancer.
PMID- 26438113
TI - To Treat or Not to Treat: The Use of Hormone Replacement Therapy in Patients With
Ovarian Cancer.
PMID- 26438115
TI - Routine Imaging for Diffuse Large B-Cell Lymphoma in First Complete Remission
Does Not Improve Post-Treatment Survival: A Danish-Swedish Population-Based
Study.
AB - PURPOSE: Routine imaging for diffuse large B-cell lymphoma (DLBCL) in first
complete remission (CR) is controversial and plays a limited role in detecting
relapse. This population-based study compared the survival of Danish and Swedish
patients with DLBCL for whom traditions for routine imaging have been different.
PATIENTS AND METHODS: Patients from the Danish and Swedish lymphoma registries
were included according to the following criteria: newly diagnosed DLBCL from
2007 to 2012, age 18 to 65 years, and CR after R-CHOP/CHOEP. Follow-up for
Swedish patients included symptom assessment, clinical examinations, and blood
tests at 3- to 4-month intervals for 2 years, with longer intervals later in
follow-up. Imaging was only recommended when relapse was clinically suspected.
Follow-up for Danish patients was similar but included routine imaging (usually
computed tomography every 6 months for 2 years). RESULTS: Danish (n = 525) and
Swedish (n = 696) patients with DLBCL had comparable baseline characteristics.
Cumulative 2-year progression rate after CR was 6% (95% CI, 4 to 9) for
International Prognostic Index (IPI) <= 2 versus 21% (95% CI, 13 to 28) for IPI >
2. Age > 60 years (hazard ratio [HR], 2.3; 95% CI, 1.6 to 3.4), elevated lactate
dehydrogenase (HR, 2.3; 95% CI, 1.4 to 3.8), B symptoms (HR, 1.7; 95% CI, 1.1 to
2.5), and Eastern Cooperative Oncology Group performance status >= 2 (HR, 1.8;
95% CI, 1.0 to 3.0) were associated with worse post-CR survival. Imaging-based
follow-up strategy had no impact on survival, neither for all patients nor for
IPI-specific subgroups. CONCLUSION: DLBCL relapse after first CR is infrequent,
and the widespread use of routine imaging in Denmark did not translate into
better survival. This favors follow-up without routine imaging and, more
generally, a shift of focus from relapse detection to improved survivorship.
PMID- 26438116
TI - To Surveil or Not to Surveil.
PMID- 26438118
TI - You've Lived a Good Life.
PMID- 26438117
TI - Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non
Small-Cell Lung Cancer and Brain Metastasis.
AB - PURPOSE: We performed a multi-institutional study to identify prognostic factors
and determine outcomes for patients with ALK-rearranged non-small-cell lung
cancer (NSCLC) and brain metastasis. PATIENTS AND METHODS: A total of 90 patients
with brain metastases from ALK-rearranged NSCLC were identified from six
institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic
radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received
tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and
intracranial progression-free survival were determined and clinical prognostic
factors were identified by Cox proportional hazards modeling. RESULTS: Median OS
after development of brain metastases was 49.5 months (95% CI, 29.0 months to not
reached), and median intracranial progression-free survival was 11.9 months (95%
CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had
progressive brain metastases at death, and repeated interventions for brain
metastases were common. Absence of extracranial metastases, Karnofsky performance
score >= 90, and no history of TKIs before development of brain metastases were
associated with improved survival (P = .003, < .001, and < .001, respectively),
whereas a single brain metastasis or initial treatment with SRS versus WBRT were
not (P = .633 and .666, respectively). Prognostic factors significant by
multivariable analysis were used to describe four patient groups with 2-year OS
estimates of 33%, 59%, 76%, and 100%, respectively (P < .001). CONCLUSION:
Patients with brain metastases from ALK-rearranged NSCLC treated with
radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that
interventions to control intracranial disease are critical. The refinement of
prognosis for this molecular subtype of NSCLC identifies a population of patients
likely to benefit from first-line SRS, close CNS observation, and treatment of
emergent CNS disease.
PMID- 26438119
TI - Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and
Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With
Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium.
AB - PURPOSE: Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line
three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction
(GEJ) adenocarcinoma and is associated with significant toxicity. We examined the
safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter
phase II study. PATIENTS AND METHODS: Previously untreated patients with
metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either
mDCF (fluorouracil 2,000 mg/m2 intravenously [IV] over 48 hours, docetaxel 40
mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 3, every 2 weeks) or parent DCF
(docetaxel 75 mg/m2, cisplatin 75 mg/m2, and fluorouracil 750 mg/m2 IV over 5
days with granulocyte colony-stimulating factor, every 3 weeks). The study had
90% power to differentiate between 6-month progression-free survival of 26% and
43%, with type I and II error rates of 10% each. An early stopping rule for
toxicity was included, defined as grade 3 to 4 adverse event rate > 70% in the
first 3 months. RESULTS: From November 2006 to June 2010, 85 evaluable patients
were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky
performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates
included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months
and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31)
closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52%
hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of
treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI,
34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6
months; P = .007). CONCLUSION: mDCF is less toxic than parent DCF, even when
supported with growth factors, and is associated with improved efficacy. mDCF
should be considered a standard first-line option for patients with metastatic
gastric or GEJ adenocarcinoma.
PMID- 26438122
TI - Towards a balanced approach to identifying conflicts of interest faced by
institutional review boards.
AB - The welfare and protection of human subjects is critical to the integrity of
clinical investigation and research. Institutional review boards (IRBs) were thus
set up to be impartial reviewers of research protocols in clinical research.
Their main role is to stand between the investigator and her human subjects in
order to ensure that the welfare of human subjects are protected. While there is
much literature on the conflicts of interest (CIs) faced by investigators and
researchers in clinical investigations, an area that is less explored is CIs that
may affect members of IRBs during the institutional ethics review of clinical
investigations. This article examines the notion of CIs in clinical research and
attempts to develop a framework for a clearer and more balanced approach to
identifying CIs that may influence members of IRBs and impede their independence.
It will also apply the proposed framework to demonstrate how IRBs possess, or at
least may appear to possess, forms of financial CIs and non-financial CIs. The
proper identification and management of these CIs is critical to preserving the
integrity of clinical investigations and achieving the primary aim of human
subjects protection.
PMID- 26438121
TI - Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding,
Distress, and Relationship With Physician Among Patients With Advanced Cancer.
AB - PURPOSE: To determine how prognostic conversations influence perceptions of life
expectancy (LE), distress, and the patient-physician relationship among patients
with advanced cancer. PATIENTS AND METHODS: This was a multicenter observational
study of 590 patients with metastatic solid malignancies with progressive disease
after >= one line of palliative chemotherapy, undergoing follow-up to death. At
baseline, patients were asked whether their oncologist had disclosed an estimate
of prognosis. Patients also estimated their own LE and completed assessments of
the patient-physician relationship, distress, advance directives, and end-of-life
care preferences. RESULTS: Among this cohort of 590 patients with advanced cancer
(median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6%
recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590
patients willing to estimate their LE, those who recalled prognostic disclosure
offered more realistic estimates as compared with patients who did not (median,
12 months; interquartile range, 6 to 36 months v 48 months; interquartile range,
12 to 180 months; P < .001), and their estimates were less likely to differ from
their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14
to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted
analyses, recall of prognostic disclosure was associated with a 17.2-month
decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE
self-estimates were associated with lower likelihood of do-not-resuscitate order
(adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate)
and preference for life-prolonging over comfort-oriented care (adjusted OR,
1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with
worse patient-physician relationship ratings, sadness, or anxiety in adjusted
analyses. CONCLUSION: Prognostic disclosures are associated with more realistic
patient expectations of LE, without decrements to their emotional well-being or
the patient-physician relationship.
PMID- 26438123
TI - Linear atrophoderma of Moulin: an underrecognized entity.
AB - Linear atrophoderma of Moulin (LAM) is an acquired skin condition that manifests
in early childhood and adolescence. It likely represents a form of cutaneous
mosaicism that presents with linear, hyperpigmented and atrophic lesions
appearing on the trunk and limbs. Its clinical appearance varies and may closely
resemble that of atrophoderma of Pasini and Pierini (APP) and linear scleroderma.
LAM usually follows a benign course and no effective treatment options exist. We
present a case of a young and healthy patient that developed such lesions on her
upper and lower extremities over 5 years. The initial clinical impression of
linear scleroderma was reviewed in favor of LAM following histological
examination of the lesions which revealed no significant inflammatory changes.
LAM remains a rare and possibly under recognized entity with reports confined
only to the dermatologic literature. This case highlights the importance of
recognizing LAM and distinguishing it from linear scleroderma given the
significant differences in management and prognosis.
PMID- 26438120
TI - Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages
of Mycosis Fungoides and Sezary Syndrome: Effect of Specific Prognostic Markers
on Survival and Development of a Prognostic Model.
AB - PURPOSE: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sezary
syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years.
Clinical management is stage based; however, there is wide range of outcome
within stages. Published prognostic studies in MF/SS have been single-center
trials. Because of the rarity of MF/SS, only a large collaboration would power a
study to identify independent prognostic markers. PATIENTS AND METHODS:
Literature review identified the following 10 candidate markers: stage, age, sex,
cutaneous histologic features of folliculotropism, CD30 positivity, proliferation
index, large-cell transformation, WBC/lymphocyte count, serum lactate
dehydrogenase, and identical T-cell clone in blood and skin. Data were collected
at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007.
Each parameter recorded at diagnosis was tested against overall survival (OS).
RESULTS: Staging data on 1,275 patients with advanced MF/SS from 29 international
sites were included for survival analysis. The median OS was 63 months, with 2-
and 5-year survival rates of 77% and 52%, respectively. The median OS for
patients with stage IIB disease was 68 months, but patients diagnosed with stage
III disease had slightly improved survival compared with patients with stage IIB,
although patients diagnosed with stage IV disease had significantly worse
survival (48 months for stage IVA and 33 months for stage IVB). Of the 10
variables tested, four (stage IV, age > 60 years, large-cell transformation, and
increased lactate dehydrogenase) were independent prognostic markers for a worse
survival. Combining these four factors in a prognostic index model identified the
following three risk groups across stages with significantly different 5-year
survival rates: low risk (68%), intermediate risk (44%), and high risk (28%).
CONCLUSION: To our knowledge, this study includes the largest cohort of patients
with advanced-stage MF/SS and identifies markers with independent prognostic
value, which, used together in a prognostic index, may be useful to stratify
advanced-stage patients.
PMID- 26438124
TI - Photofragmentation of the Gas-Phase Lanthanum Isopropylcyclopentadienyl Complex:
Computational Modeling vs Experiment.
AB - Photofragmentation of the lanthanum isopropylcyclopentadienyl complex, La(iCp),
was explored through time-dependent excited-state molecular dynamics (TDESMD),
excited-state molecular dynamics (ESMD), and thermal molecular dynamics (MD).
Simulated mass spectra were extracted from ab initio molecular dynamics
simulations through a new and simple method and compared to experimental
photoionization time-of-flight (PI-TOF) mass spectra. The computational results
indicate that the value of excitation energy and mechanism of excitation
determine the dissociation process.
PMID- 26438125
TI - Proteomic analysis of the influence of Cu(2+) on the crystal protein production
of Bacillus thuringiensis X022.
AB - BACKGROUND: Bacillus thuringiensis X022, a novel strain isolated from soil in
China, produces diamond-shaped parasporal crystals. Specific mineral nutrients,
such as Mg, Cu, and Mn, influence insecticidal crystal proteins (ICP) expression
and the effects of these elements vary significantly. However, the molecular
mechanisms of the effects caused by mineral elements have yet to be reported.
RESULTS: The ICP are mainly composed of Cry1Ca, Cry1Ac, and Cry1Da, which have
molecular weights of about 130 kDa. ICP production was most efficient when Cu(2+)
was added at concentrations ranging from 10(-6) to 10(-4) mol/L at an initial pH
of 8.0. Addition of Cu(2+) also evidently increased the toxicity of fermentation
broth to Spodoptera exigua and Helicoverpa armigera. After analyzing changes in
proteome and fermentation parameters caused by Cu(2+) addition, we propose that
Cu(2+) increases PhaR expression and consequently changes the carbon flow. More
carbon sources was used to produce intracellular poly-beta-hydroxybutyrate (PHB).
Increases in PHB as a storage material bring about increases of ICP production.
CONCLUSIONS: Bacillus thuringiensis X022 mainly expresses Cry1Ca, Cry1Ac, and
Cry1Da. Cu(2+) increases the expression of Cry1Da, Cry1Ca, and also enhances the
toxicity of fermentation broth to S. exigua and H. armigera.
PMID- 26438126
TI - High Throughput In Situ DDA Analysis of Neuropeptides by Coupling Novel Multiplex
Mass Spectrometric Imaging (MSI) with Gas-Phase Fractionation.
AB - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometric imaging
(MSI) is a powerful tool to map the spatial distribution of biomolecules on
tissue sections. Recent developments of hybrid MS instruments allow combination
of different types of data acquisition by various mass analyzers into a single
MSI analysis, which reduces experimental time and sample consumptions. Here,
using the well-characterized crustacean nervous system as a test-bed, we explore
the utility of high resolution and accurate mass (HRAM) MALDI Orbitrap platform
for enhanced in situ characterization of the neuropeptidome with improved
chemical information. Specifically, we report on a multiplex-MSI method, which
combines HRAM MSI with data dependent acquisition (DDA) tandem MS analysis in a
single experiment. This method enables simultaneous mapping of neuropeptide
distribution, sequence validation, and novel neuropeptide discovery in crustacean
neuronal tissues. To enhance the dynamic range and efficiency of in situ DDA, we
introduced a novel approach of fractionating full m/z range into several sub-mass
ranges and embedding the setup using the multiplex-DDA-MSI scan events to
generate pseudo fractionation before MS/MS scans. The division of entire m/z into
multiple segments of m/z sub-ranges for MS interrogation greatly decreased the
complexity of molecular species from tissue samples and the heterogeneity of the
distribution and variation of intensities of m/z peaks. By carefully optimizing
the experimental conditions such as the dynamic exclusion, the multiplex-DDA-MSI
approach demonstrates better performance with broader precursor coverage, less
biased MS/MS scans towards high abundance molecules, and improved quality of
tandem mass spectra for low intensity molecular species. Graphical Abstract ?.
PMID- 26438127
TI - Focus on Mass Spectrometry-Based Strategies for Neuroproteomics and Peptidomics,
Honoring Dr. Lingjun Li, Recipient of the 2014 ASMS Biemann Medal.
PMID- 26438128
TI - Benzylammonium Thermometer Ions: Internal Energies of Ions Formed by Low
Temperature Plasma and Atmospheric Pressure Chemical Ionization.
AB - The extent of internal energy deposition upon ion formation by low temperature
plasma and atmospheric pressure chemical ionization was investigated using novel
benzylammonium thermometer ions. C-N heterolytic bond dissociation enthalpies of
nine 4-substituted benzylammoniums were calculated using CAM-B3LYP/6-311++G(d,p),
which was significantly more accurate than B3LYP/6-311++G(d,p), MP2/6
311++G(d,p), and CBS-QB3 for calculating the enthalpies of 20 heterolytic
dissociation reactions that were used to benchmark theory. All 4-substituted
benzylammonium thermometer ions fragmented by a single pathway with comparable
dissociation entropies, except 4-nitrobenzylammonium. Overall, the extent of
energy deposition into ions formed by low temperature plasma was significantly
lower than those formed by atmospheric pressure chemical ionization under these
conditions. Because benzylamines are volatile, this new suite of thermometer ions
should be useful for investigating the extent of internal energy deposition
during ion formation for a wide range of ionization methods, including plasma,
spray and laser desorption-based techniques. Graphical Abstract ?.
PMID- 26438130
TI - Paramedicine students' perception of preparedness for clinical placement in
Australia and New Zealand.
AB - BACKGROUND: Clinical placement is an essential element of paramedicine education
and training as the profession completes the transition from vocational training
to a pre-employment, university based model. The objective of this study was to
survey pre-employment paramedicine students at Universities in Victoria,
Australia and Auckland, New Zealand to measure their self-assessed preparedness
for clinical placement. METHODS: This was a cross-sectional study involving paper
based questionnaires employing a convenience sample of 682 undergraduate
paramedicine students (years 1-4) who had completed at least one clinical
placement. Student perceptions of preparedness for clinical placement were
measured using an adaptation of the 'Preparedness for Hospital Practice'
questionnaire. RESULTS: There are significant differences in students' perception
of preparedness for clinical placement, which reflects the differences between
universities in relation to structure of their paramedicine programs, the timing
of clinical education and the number of hours of clinical placement. DISCUSSION:
There needs to be clinical placement agreements between the ambulance services
and universities that clearly describe the standards and expected elements of a
quality clinical placement. CONCLUSIONS: In order to improve the preparedness for
placement for paramedicine students, a united approach is required by all
stakeholders, including ambulance services, students and universities.
PMID- 26438129
TI - Perioperative smoking cessation in vascular surgery: challenges with a randomized
controlled trial.
AB - BACKGROUND: The effect of intensive smoking cessation programs on postoperative
complications has never before been assessed in soft tissue surgery when smoking
cessation is initiated on the day of surgery. METHODS: A single-blinded
randomized clinical trial conducted at two vascular surgery departments in
Denmark. The intervention group was offered the Gold Standard Program (GSP) for
smoking cessation intervention. The control group was offered the departments'
standard care. Inclusion criteria were patients with planned open peripheral
vascular surgery and who were daily smokers. According to the power calculation a
total of 144 patients were needed in the trial. RESULTS: Due to slow patient
inclusion, the trial was terminated prior to fulfilling the power calculation.
Thirty-two patients were included in the trial from March 2011 to September 2012.
Of these, 11 were randomized to the GSP intervention and 21 as controls. There
was no difference in 30-day complication rates or 6-week abstinence rates between
the two groups. CONCLUSIONS: A trial assessing the effect of smoking cessation on
postoperative complications on the day of soft tissue surgery is still needed. If
another trial is to be planned it must be more pragmatic with less extended
inclusion criteria and conducted nationally or internationally to ensure enough
patients for the trial. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01469091 ).
Registration date: 27 October 2011.
PMID- 26438131
TI - Construction of the BAC Library of Small Abalone (Haliotis diversicolor) for Gene
Screening and Genome Characterization.
AB - The small abalone (Haliotis diversicolor) is one of the most important
aquaculture species in East Asia. To facilitate gene cloning and
characterization, genome analysis, and genetic breeding of it, we constructed a
large-insert bacterial artificial chromosome (BAC) library, which is an important
genetic tool for advanced genetics and genomics research. The small abalone BAC
library includes 92,610 clones with an average insert size of 120 Kb, equivalent
to approximately 7.6* of the small abalone genome. We set up three-dimensional
pools and super pools of 18,432 BAC clones for target gene screening using PCR
method. To assess the approach, we screened 12 target genes in these 18,432 BAC
clones and identified 16 positive BAC clones. Eight positive BAC clones were then
sequenced and assembled with the next generation sequencing platform. The
assembled contigs representing these 8 BAC clones spanned 928 Kb of the small
abalone genome, providing the first batch of genome sequences for genome
evaluation and characterization. The average GC content of small abalone genome
was estimated as 40.33%. A total of 21 protein-coding genes, including 7 target
genes, were annotated into the 8 BACs, which proved the feasibility of PCR
screening approach with three-dimensional pools in small abalone BAC library. One
hundred fifty microsatellite loci were also identified from the sequences for
marker development in the future. The BAC library and clone pools provided
valuable resources and tools for genetic breeding and conservation of H.
diversicolor.
PMID- 26438132
TI - Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type
natriuretic in patients with ST-elevation myocardial infarction treated by
primary PCI: a prospective observational cohort study.
AB - OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) from a
pathophysiological perspective connects various pathways that affect the
prognosis after myocardial infarction. The objective was to evaluate the benefits
of measuring NGAL for prognostic stratification in addition to the Thrombolysis
in Myocardial Infarction (TIMI) score, and to compare it with the prognostic
value of B-type natriuretic peptide (BNP). DESIGN: Prospective observational
cohort study. SETTING: One university/tertiary centre. PARTICIPANTS: A total of
673 patients with ST segment elevation myocardial infarction were treated by
primary percutaneous coronary intervention. NGAL and BNP were assessed on
hospital admission. OUTCOMES: PRIMARY OUTCOME: 1-year mortality. SECONDARY
OUTCOMES: 1-year hospitalisation due to acute heart failure, unplanned
revascularisation, reinfarction, stroke and combined end point of 1-year
mortality and hospitalisation due to heart failure. STATISTICAL METHODS: Using
the c-statistic, the ability of NGAL, BNP and TIMI score to predict 1-year
mortality alone and in combination with readmission for heart failure was
evaluated. The addition of the predictive value of biomarkers to the score was
assessed by category free net reclassification improvement (cfNRI) and the
integrated discrimination index (IDI). RESULTS: The NGAL level was significantly
higher in non-survivors (67 vs 115 pg/mL; p<0.001). The area under the curve
(AUC) values for mortality prediction for NGAL, BNP and TIMI score were 75.5,
78.7 and 74.4, respectively (all p<0.001) with optimal cut-off values of 84 pg/mL
for NGAL and 150 pg/mL for BNP. The addition of NGAL and BNP to the TIMI score
significantly improved risk stratification according to cfNRI and IDI. A BNP and
the combination of the TIMI score with NGAL predicted the occurrence of the
combined end point with an AUC of 80.6 or 82.2, respectively. NGAL alone is a
simple tool to identify very high-risk patients. NGAL >110 pg/mL was associated
with a 1-year mortality of 20%. CONCLUSIONS: The measurement of NGAL together
with the TIMI score results in a strong prognostic model for the 1-year mortality
rate in patients with STEMI.
PMID- 26438133
TI - Studying the time trend of Methicillin-resistant Staphylococcus aureus (MRSA) in
Norway by use of non-stationary gamma-Poisson distributions.
AB - OBJECTIVES: Study the time development of methicillin-resistant Staphylococcus
aureus (MRSA) and forecast future behaviour. The major question: Is the number of
MRSA isolates in Norway increasing and will it continue to increase? DESIGN: Time
trend analysis using non-stationary gamma-Poisson distributions. SETTING: Two
data sets were analysed. The first data set (data set I) consists of all MRSA
isolates collected in Oslo County from 1997 to 2010; the study area includes the
Norwegian capital of Oslo and nearby surrounding areas, covering approximately
11% of the Norwegian population. The second data set (data set II) consists of
all MRSA isolates collected in Health Region East from 2002 to 2011. Health
Region East consists of Oslo County and four neighbouring counties, and is the
most populated area of Norway. PARTICIPANTS: Both data sets I and II consist of
all persons in the area and time period described in the Settings, from whom MRSA
have been isolated. PRIMARY AND SECONDARY OUTCOME MEASURES: MRSA infections have
been mandatory notifiable in Norway since 1995, and MRSA colonisation since 2004.
In the time period studied, all bacterial samples in Norway have been sent to a
medical microbiological laboratory at the regional hospital for testing. In
collaboration with the regional hospitals in five counties, we have collected all
MRSA findings in the South-Eastern part of Norway over long time periods.
RESULTS: On an average, a linear or exponential increase in MRSA numbers was
observed in the data sets. A Poisson process with increasing intensity did not
capture the dispersion of the time series, but a gamma-Poisson process showed
good agreement and captured the overdispersion. The numerical model showed
numerical internal consistency. CONCLUSIONS: In the present study, we find that
the number of MRSA isolates is increasing in the most populated area of Norway
during the time period studied. We also forecast a continuous increase until the
year 2017.
PMID- 26438134
TI - A systematic review protocol for reporting deficiencies within surgical case
series.
AB - INTRODUCTION: Case series are an important and common study type in surgical
literature. There is evidence that key data are excluded from published case
series, and currently no reporting guideline exists for case series. There is,
therefore, the potential to change practices and improve the reporting of case
series. Reporting guidelines have been shown to be efficacious in raising the bar
for reporting quality. We present our protocol for the first stage of guideline
development--a systematic review of previously identified deficiencies in how
surgical case series are reported. METHODS AND ANALYSIS: Electronic searches will
be conducted on MEDLINE, EMBASE, Cochrane Methods Register, Science Citation
Index and Conference Proceedings Citation Index, from the start of indexing until
5 November 2014. The electronic search strategy was developed with an information
specialist. Two independent researchers will identify articles for inclusion,
specifically those that describe reporting deficiencies within surgical case
series. Data will be extracted to specifically focus on the deficiencies of
reporting. These will be categorised according to their type, and other
identified issues will also be presented. Data will be presented with descriptive
statistics to determine frequently missing types of data, and the commonest
reporting issues tabulated. ETHICS AND DISSEMINATION: The authors hope to
disseminate the findings as widely as possible, irrespective of results, as these
will add to the wider corpora of information on this subject. The systematic
review will be published in a peer-reviewed journal and will be presented at a
wide range of national and international conferences. Ultimately, this will
inform a Delphi process for the development of a surgical case series reporting
guideline. PROTOCOL REGISTRATION: CRD42015016145.
PMID- 26438135
TI - Willingness to pay per quality-adjusted life year for life-saving treatments in
Thailand.
AB - OBJECTIVE: To estimate the willingness to pay (WTP) per quality-adjusted life
year (QALY) value for life-saving treatments and to determine factors affecting
the WTP per QALY value. DESIGN: A cross-sectional survey with multistage sampling
and face-to-face interviews. SETTING: General population in the southern part of
Thailand. PARTICIPANTS: A total of 600 individuals were included in the study.
Only 554 (92.3%) responses were usable for data analyses. OUTCOME MEASURE:
Participants were asked for the maximum amount of WTP value for life-saving
treatments by an open-ended question. EQ-5D-3L and visual analogue scale (VAS)
were used to estimate additional QALY. RESULTS: The amount of WTP values varied
from 0 to 720,000 Baht/year (approximately 32 Baht=US$1). The averages of
additional QALY obtained from VAS and EQ-5D-3L were only slightly different
(0.872 and 0.853, respectively). The averages of WTP per QALY obtained from VAS
and EQ-5D-3L were 244,720 and 243,120 Baht/QALY, respectively. As compared to
male participants, female participants were more likely to pay less for an
additional QALY (p=0.007). In addition, participants with higher household
incomes tended to have higher WTP per QALY values (p<0.001). CONCLUSIONS: Our
study added another WTP per QALY value specifically for life-saving treatments,
which would complement the current cost-effectiveness threshold used in Thailand
and optimise patient access to innovative treatments or technologies.
PMID- 26438136
TI - Association between COX-2 gene polymorphisms and risk of hepatocellular carcinoma
development: a meta-analysis.
AB - OBJECTIVE: To investigate the association between cyclo-oxygenase-2 (COX-2)
polymorphism and the risk of hepatocellular carcinoma (HCC) development. DESIGN:
Systematic review and meta-analysis of COX-2 polymorphism and risk of HCC
development among people with or without HCC. DATA SOURCES: EMBASE, PubMed,
Public Library of Science, SCOPUS, Web of Knowledge and Chinese National
Knowledge Infrastructure were searched for all clinical and experimental case
control studies of COX-2 polymorphism and HCC risk. Studies published up to March
2015 were included. REVIEW METHOD: Ten studies were included for data extraction,
which were mainly from Asian countries. RESULTS: 2538 people with HCC and 3714
without HCC were found to satisfy the inclusion criteria and included in the
review. The associations of specific genotypes in the eight polymorphic variants
of COX-2 and the risk of HCC development were analysed. GG genotype at the A
1195G polymorphism may be associated with a reduced risk of HCC development: the
OR across all studies was 0.87 (95% CI 0.75 to 1.02) for the G allele versus the
A allele, 0.72 (0.53 to 0.97) for GG versus AA, 0.72 (0.57 to 0.92) for GG versus
GA+AA and 1.05 (0.77 to 1.44) for AA versus GA+GG. Similar results were found
when the meta-analysis was repeated separately for the Chinese subgroup. However,
more reliable data are needed to demonstrate associations between variants in G
765C, T+8473C, A-1290G, G-899C and introns 1, 5 and 6 polymorphisms and the risk
of HCC development. CONCLUSIONS: Only the COX-2 A-1195G gene polymorphism may be
associated with a decreased risk of HCC development. These conclusions should be
verified in further studies.
PMID- 26438137
TI - Micronutrient deficiencies and developmental delays among infants: evidence from
a cross-sectional survey in rural China.
AB - OBJECTIVES: Research increasingly indicates the importance of the nutritional
programming that occurs in the first 2-3 years of life. Quality nutrition during
this brief window has been shown to have large and significant effects on health
and development throughout childhood and even into adulthood. Despite the
widespread understanding of this critical window, and the long-term consequences
of leaving nutritional deficiencies unaddressed, little is known about the status
of infant nutrition in rural China, or about the relationship between infant
nutrition and cognitive development in rural China. DESIGN, SETTING AND
PARTICIPANTS: In April 2013 and October 2013, we conducted a survey of 1808
infants aged 6-12 months living in 351 villages across 174 townships in
nationally designated poverty counties in rural areas of southern Shaanxi
Province, China. MAIN OUTCOME MEASURES: Infants were administered a finger prick
blood test for haemoglobin and assessed according to the Bayley Scales of Infant
Development. They were also measured for length and weight. Caregivers were
administered a survey of demographic characteristics and feeding practices.
RESULTS: We found that 48.8% of sample infants were anaemic, 3.7% were stunted,
1.2% were underweight and 1.6% were wasted. Approximately 20.0% of the sample
infants were significantly delayed in their cognitive development, while just
over 32.3% of the sample infants were significantly delayed in their psychomotor
development. After controlling for potential confounders, infants with lower
haemoglobin counts were significantly more likely to be delayed in both their
cognitive (p<0.01) and psychomotor development (p<0.01). CONCLUSIONS: The anaemia
rates that we identify in this study classify anaemia as a 'severe' public health
problem according to the WHO. In contrast, there is virtually no linear growth
failure among this population. We find that low haemoglobin levels among our
sample population are associated with significant cognitive and psychomotor
delays that could eventually affect children's schooling performance and labour
force outcomes. TRIAL REGISTRATION NUMBER: ISRCTN44149146.
PMID- 26438138
TI - Self-reported sleep in late pregnancy in relation to birth size and fetal
distress: the E Moe, Mama prospective cohort study.
AB - OBJECTIVES: To explore associations between features of sleep during pregnancy
and adverse outcomes for the infant. SETTING: E Moe, Mama is a cohort study in
Aotearoa/New Zealand that investigates self-reported sleep and maternal health in
late pregnancy and the postpartum period. PARTICIPANTS: Women (N=633; 194 Maori)
reported detailed information on their sleep duration, quality, disturbances,
disorders (snoring, breathing pauses, twitching legs, restless legs) and daytime
sleepiness between 35 and 37 weeks gestation. OUTCOME MEASURES: Birthweight and
fetal distress during labour were extracted from medical records. Associations
between each sleep variable and small or large for gestational age (SGA/LGA)
using customised birthweight centile or fetal distress were estimated using
multinomial/logistic regression, controlling for potential confounders. Secondary
analyses considered differences in associations between Maori and non-Maori
women. RESULTS: There was some indication that breathing pauses (a measure of
sleep apnoea) were associated with both SGA (OR 2.8, 95% CI 0.9 to 9.0, p=0.08)
and LGA (OR 2.0, 95% CI 0.7 to 5.7, p=0.20), with the association for LGA being
stronger when only pregnancy-onset breathing pauses were considered (OR 3.5, 95%
CI 1.3 to 9.6, p=0.01). There was also some evidence that pregnancy-onset leg
twitching (OR 3.3, 95% CI 1.1 to 10.0, p=0.03) and frequent sleep disturbance due
to feeling too hot or too cold (OR 1.7, 95% CI 0.9 to 3.6, p=0.13) were
associated with higher risk of fetal distress. Other sleep measures, including
snoring, were not associated with SGA, LGA or fetal distress. Many of the
associations we observed were considerably stronger in Maori compared with non
Maori women. CONCLUSIONS: We did not find evidence of previously reported
associations between snoring and SGA. Our findings tentatively suggest that self
reported breathing pauses and leg twitching in late pregnancy are associated with
infant outcomes, and highlight ethnic inequalities.
PMID- 26438139
TI - Assessment of mental health literacy using a multifaceted measure among a Chinese
rural population.
AB - OBJECTIVES: The present study aims to assess mental health literacy (MHL) using a
standardised multifaceted 20-item instrument called Mental Health Knowledge
Questionnaire (MHKQ) developed by the Chinese Ministry of Health, among a rural
Chinese population. SETTING: Four villages in Liuyang county of Hunan province,
China. PARTICIPANTS: This was a cross-sectional study. A multistage cluster
sampling method was adopted, leading to a final sampling frame of 2377 residents
aged 18-60 years from four villages of Liuyang county. Included in the study were
residents aged 18-60 years living in their village for at least half a year;
excluded were those not living in the areas during the research period, those
with difficulty in communication due to serious physical or mental illness and
those who were cognitively impaired or actively psychotic. Finally, 2052
participants completed the survey. PRIMARY AND SECONDARY OUTCOME MEASURES:
Primary outcome was correct response rate of the MHKQ; secondary outcome measures
were association between sociodemographics and MHL, and association between MHL
and health outcomes. RESULTS: Correct response rates for the 20 MHKQ items ranged
from 19% to 94%, with a mean rate of 58%. Younger age (r=-0.02, p<0.01), higher
education (r: 1.38-2.69, p<0.01) and higher income (r=0.41, p<0.01), were
independently associated with higher MHL. MHL was independently associated with
self-rated general health (r=2.31, p<0.01), depression (r=-0.09, p<0.01) and
anxiety (r=-0.07, p<0.05). CONCLUSIONS: MHL in the rural areas of Liuyang is
lower than that reported in urban areas of China. There is much room for
improvement with regard to MHL promotion in rural areas of China. Younger age,
higher education and higher income are the three robust factors related to higher
MHL, so cohort-specific educational intervention efforts may be indicated.
PMID- 26438140
TI - Increased planned delivery contributes to declining rates of pregnancy
hypertension in Australia: a population-based record linkage study.
AB - OBJECTIVE: Since the 1990s, pregnancy hypertension rates have declined in some
countries, but not all. Increasing rates of early planned delivery (before the
due date) have been hypothesised as the reason for the decline. The aim of this
study was to explore whether early planned delivery can partly explain the
declining pregnancy hypertension rates in Australia. DESIGN: Population-based
record linkage study utilising linked birth and hospital records. SETTING AND
PARTICIPANTS: A cohort of 1,076,122 deliveries in New South Wales, Australia,
2001-2012. OUTCOME MEASURES: Pregnancy hypertension (including gestational
hypertension, pre-eclampsia and eclampsia) was the main outcome; pre-eclampsia
was a secondary outcome. RESULTS: From 2001 to 2012, pregnancy hypertension rates
declined by 22%, from 9.9% to 7.7%, and pre-eclampsia by 27%, from 3.3% to 2.4%
(trend p<0.0001). At the same time, planned deliveries increased: prelabour
caesarean section by 43% (12.9-18.4%) and labour inductions by 10% (24.8-27.2%).
Many maternal risk factors for pregnancy hypertension significantly increased
(p<0.01) over the study period including nulliparity, age >=35 years, diabetes,
overweight and obesity, and use of assisted reproductive technologies; some risk
factors decreased including multifetal pregnancies, age <20 years, autoimmune
diseases and previous pregnancy hypertension. Given these changes in risk
factors, the pregnancy hypertension rate was predicted to increase to 10.5%.
Examination of annual gestational age distributions showed that pregnancy
hypertension rates actually declined from 38 weeks gestation and were steepest
from 41 weeks; at least 36% of the decrease could be attributed to planned
deliveries. The risk factors for pregnancy hypertension were also risk factors
for planned delivery. CONCLUSIONS: It appears that an unanticipated consequence
of increasing early planned deliveries is a decline in the incidence of pregnancy
hypertension. Women with risk factors for hypertension were relatively more
likely to be selected for early delivery.
PMID- 26438141
TI - Prognostic and functional importance of the engraftment-associated genes in the
patient-derived xenograft models of triple-negative breast cancers.
AB - We aimed to identify the factors affecting the successful tumor engraftment in
breast cancer patient-derived xenograft (PDX) models. Further, we investigated
the prognostic significance and the functional importance of the PDX engraftment
related genes in triple-negative breast cancers (TNBC). The clinico-pathologic
features of 81 breast cancer patients whose tissues were used for PDX
transplantation were analyzed to identify the factors affecting the PDX
engraftment. A gene signature associated with the PDX engraftment was discovered
and its clinical importance was tested in a publicly available dataset and in
vitro assays. Nineteen out of 81 (23.4 %) transplanted tumors were successfully
engrafted into the PDX models. The engraftment rate was highest in TNBC when
compared to other subtypes (p = 0.001) and in recurrent or chemotherapy-resistant
tumors compared to newly diagnosed primary tumors (p = 0.024). PDX tumors
originated from the TNBC cases showed more rapid tumor growth in mice. Gene
expression profiling showed that down-regulation of genes involved in the tumor
immune interaction was significantly associated with the successful PDX
engraftment. The engraftment gene signature was associated with worse survival
outcome when tested in publicly available mRNA datasets of TNBC cases. Among the
engraftment-related genes, PHLDA2, TKT, and P4HA2 showed high expression in
triple-negative breast cancer cell lines, and siRNA-based gene silencing resulted
in reduced cell invasion and proliferation in vitro. Our results show that the
PDX engraftment may reflect the aggressive phenotype in breast cancer. Genes
associated with the PDX engraftment may provide a novel prognostic biomarker and
therapeutic targets in TNBC.
PMID- 26438142
TI - Comparison of methods to detect the in vitro activity of silver nanoparticles
(AgNP) against multidrug resistant bacteria.
AB - BACKGROUND: Multidrug resistant microorganisms are a growing challenge and new
substances that can be useful to treat infections due to these microorganisms are
needed. Silver nanoparticle may be a future option for treatment of these
infections, however, the methods described in vitro to evaluate the inhibitory
effect are controversial. RESULTS: This study evaluated the in vitro activity of
silver nanoparticles against 36 susceptible and 54 multidrug resistant Gram
positive and Gram-negative bacteria from clinical sources. The multidrug
resistant bacteria were oxacilin-resistant Staphylococcus aureus, vancomycin
resistant Enterococcus spp., carbapenem- and polymyxin B-resistant A. baumannii,
carbapenem-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae.
We analyzed silver nanoparticles stabilized with citrate, chitosan and polyvinyl
alcohol and commercial silver nanoparticle. Silver sulfadiazine and silver
nitrate were used as control. Different methods were used: agar diffusion,
minimum inhibitory concentration, minimum bactericidal concentration and time
kill. The activity of AgNPs using diffusion in solid media and the MIC methods
showed similar effect against MDR and antimicrobial-susceptible isolates, with a
higher effect against Gram-negative isolates. The better results were achieved
with citrate and chitosan silver nanoparticle, both with MIC90 of 6.75 MUg mL(
1), which can be due the lower stability of these particles and, consequently,
release of Ag(+) ions as revealed by X-ray diffraction (XRD). The bactericidal
effect was higher against antimicrobial-susceptible bacteria. CONCLUSION: It
seems that agar diffusion method can be used as screening test, minimum
inhibitory concentration/minimum bactericidal concentration and time kill showed
to be useful methods. The activity of commercial silver nanoparticle and silver
controls did not exceed the activity of the citrate and chitosan silver
nanoparticles. The in vitro inhibitory effect was stronger against Gram-negative
than Gram-positive, and similar against multidrug resistant and susceptible
bacteria, with best result achieved using citrate and chitosan silver
nanoparticles. The bactericidal effect of silver nanoparticle may, in the future,
be translated into important therapeutic and clinical options, especially
considering the shortage of new antimicrobials against the emerging antimicrobial
resistant microorganisms, in particular against Gram-negative bacteria.
PMID- 26438143
TI - Defining cancer-related fatigue for biomarker discovery.
PMID- 26438144
TI - Cancer patients' respect experiences in relation to perceived communication
behaviours from hospital staff: analysis of the 2012-2013 National Cancer Patient
Experience Survey.
AB - PURPOSE: Respect experiences are poorly understood despite respect being central
to professionalism in health care and patient well-being, and needed for optimal
patient care. This study explores which patient-perceived communication
behaviours from hospital staff contribute most to cancer patients' respect
experiences and account for variation in their experience by socio-demographic
and clinical characteristics. METHODS: We present a secondary analysis of data
from the 2012-2013 National Cancer Patient Experience Survey of 45,191 patients
with a primary cancer diagnosis treated in English National Health Service trusts
providing adult acute cancer services who provided data on experienced respect
and dignity. RESULTS: Both autonomy-supportive and caring/emotionally sensitive
behaviours were associated with reported respect, although the latter showed
stronger associations and accounted for most differences in reports of respect
between patient groups. Differences in respect were found by gender,
race/ethnicity, age, the presence of long-standing conditions, treatment
response, time since first treated for cancer (p < .001), employment and type of
cancer (p < .05). CONCLUSIONS: The study questions the tendency to conceptualise
respect primarily in terms of autonomy-supportive behaviours and shows the
relative contribution of autonomy-supportive and caring/emotionally sensitive
behaviours in explaining disparities in respect experiences. More attention
should be paid to affective communication behaviours from hospital staff to
reduce disparities in respect experiences.
PMID- 26438145
TI - Breakthrough pain and its treatment: critical review and recommendations of IOPS
(Italian Oncologic Pain Survey) expert group.
AB - Controversies exist about the definition and epidemiology of breakthrough cancer
pain (BTcP), the pharmacological treatment options, drug dosing, and how to
select the medications for BTcP among the new fentanyl products. Existing data
were critically evaluated to provide recommendations by an expert group. An
algorithm to diagnose BTcP should be used followed by a careful assessment.
Fentanyl products provide efficacy and rapidity of action to counteract the
temporal pattern of BTcP. The doses of opioids used for background pain should
guide the choice of the doses of fentanyl products. The choice of fentanyl
products should be based on individual clinical conditions.
PMID- 26438147
TI - Psychological distress, optimism and general health in breast cancer survivors: a
data linkage study using the Scottish Health Survey.
AB - PURPOSE: The aim of this study is to examine the association between optimism and
psychological distress in women with breast cancer after taking into account
their self-rated general health. METHODS: Data were aggregated from the Scottish
Health Survey (2008 to 2011) to derive a nationally representative sample of
12,255 women (11,960 cancer-free controls, and 295 breast cancer cases identified
from linked cancer registry data). The explanatory variables were optimism and
general health, and the outcome variable was symptoms of psychological distress.
Logistic regression analyses were conducted, with optimism entered in step 1 and
general health entered in step 2. RESULTS: In an unadjusted model, higher levels
of optimism were associated with lower odds of psychological distress in both the
control group (OR = 0. 57, 95 % CI = 0.51-0.60) and breast cancer group (OR = 0.
64, 95 % CI = 0.47-0.88). However, in a model adjusting for general health,
optimism was associated with lower odds of psychological distress only in the
control group (OR = 0.50, 95 % CI = 0.44-0.57), but not significantly in the
breast cancer group (OR = 1.15, 95 % CI = 0.32-4.11). In the breast cancer group,
poor general health was a stronger associate of psychological distress (OR = 4.
98, 95 % CI = 1.32-18.75). Results were consistent after adjusting for age, years
since breast cancer diagnosis, survey year, socioeconomic status, education,
marital status, body mass index, smoking status, and alcohol consumption.
CONCLUSION: This research confirms the value of multicomponent supportive care
interventions for women with breast cancer. Specifically, it suggests that
following breast cancer diagnosis, health care professionals need to provide
advice and signpost to services that assist women to maintain or improve both
their psychological and general health.
PMID- 26438148
TI - A telephone survey of factors affecting willingness to participate in health
research surveys.
AB - BACKGROUND: In recent years, reduced participation has been encountered across
all epidemiological study designs, both in terms of non-response as well as
refusal. A low response rate may reduce the statistical power but, more
importantly, results may not be generalizable to the wider community. METHODS: In
a telephone survey of 1413 randomly selected members of the Australian general
population and of 690 participants sourced from previous studies, we examined
factors affecting people's stated willingness to participate in health research.
RESULTS: The majority of participants (61 %) expressed willingness to participate
in health research in general but the percentage increased when provided with
more specific information about the research. People were more willing if they
have personal experience of the disease under study, and if the study was funded
by government or charity rather than pharmaceutical companies. Participants from
previous studies, older people and women were the groups most willing to
participate. Younger men preferred online surveys, older people a written
questionnaire, and few participants in any age and sex groups preferred a
telephone questionnaire. CONCLUSION: Despite a trend toward reduced participation
rates, most participants expressed their willingness to participate in health
research. However, when seeking participants, researchers should be concrete and
specific about the nature of the research they want to carry out. The preferred
method of recommended contact varies with the demographic characteristics.
PMID- 26438146
TI - Effect of patient navigation on satisfaction with cancer-related care.
AB - PURPOSE: Despite growing popularity of patient navigation (PN) as a means to
improve cancer care quality and reduce cancer-related disparities, there are few
well-designed controlled trials assessing the impact of PN on patient outcomes
like satisfaction with care. The present controlled study examined effect of PN
on satisfaction with cancer-related care. METHODS: Patients who presented with a
symptom or abnormal screening test (n = 1788) or definitive diagnosis (n = 445)
of breast, cervical, colorectal, or prostate cancer from eight Patient Navigator
Research Program sites were included in one of two groups: intervention (PN) or
comparison (usual care or usual care plus cancer educational materials). Trained
patient navigators met with intervention group participants to help them assess
and identify resources to address barriers to cancer diagnostic or treatment
care. Using a validated instrument, we assessed participants' satisfaction with
their cancer diagnostic or treatment care up to 3 months after diagnostic
resolution of a cancer-related abnormality or within 3 months of initiation of
cancer treatment. RESULTS: Overall, patients reported high satisfaction with
diagnostic care and cancer treatment. There were no statistically significant
differences between PN and control groups in satisfaction with cancer-related
care (p > 0.05). Hispanic and African American participants were less likely to
report high satisfaction with cancer care when compared to White patients. Middle
aged participants with higher education, higher household income, private
insurance, owning their own home, working full-time, and those whose primary
language is English had higher satisfaction with cancer-related diagnostic care.
CONCLUSIONS: PN had no statistically significant effect on patients' satisfaction
with cancer-related care. Further research is needed to define the patient
populations who might benefit from PN, content of PN that is most useful, and
services that might enhance PN. TRIAL REGISTRATIONS: clinicaltrials.gov
identifiers: NCT00613275 , NCT00496678 , NCT00375024 , NCT01569672.
PMID- 26438149
TI - Low temperature-induced DNA hypermethylation attenuates expression of RhAG, an
AGAMOUS homolog, and increases petal number in rose (Rosa hybrida).
AB - BACKGROUND: Flower development is central to angiosperm reproduction and is
regulated by a broad range of endogenous and exogenous stimuli. It has been well
documented that ambient temperature plays a key role in controlling flowering
time; however, the mechanisms by which temperature regulates floral organ
differentiation remain largely unknown. RESULTS: In this study, we show that low
temperature treatment significantly increases petal number in rose (Rosa hybrida)
through the promotion of stamen petaloidy. Quantitative RT-PCR analysis revealed
that the expression pattern of RhAG, a rose homolog of the Arabidopsis thaliana
AGAMOUS C-function gene, is associated with low temperature regulated flower
development. Silencing of RhAG mimicked the impact of low temperature treatments
on petal development by significantly increasing petal number through an
increased production of petaloid stamens. In situ hybridization studies further
revealed that low temperature restricts its spatial expression area. Analysis of
DNA methylation level showed that low temperature treatment enhances the
methylation level of the RhAG promoter, and a specific promoter region that was
hypermethylated at CHH loci under low temperature conditions, was identified by
bisulfite sequencing. This suggests that epigenetic DNA methylation contributes
to the ambient temperature modulation of RhAG expression. DISCUSSION: Our results
provide highlights in the role of RhAG gene in petal number determination and add
a new layer of complexity in the regulation of floral organ development.
CONCLUSIONS: We propose that RhAG plays an essential role in rose flower
patterning by regulating petal development, and that low temperatures increase
petal number, at least in part, by suppressing RhAG expression via enhancing DNA
CHH hypermethylation of the RhAG promoter.
PMID- 26438151
TI - The common NOD2/CARD15 variant P268S in patients with non-infectious uveitis: a
cohort study.
AB - BACKGROUND: The etiology of Autoimmune chronic uveitis (ACU) is still unknown;
NOD2/CARD15 gene mutations are responsible for the Blau Syndrome and can induce
uveitis in animal models. PRESENTATION OF THE HYPOTHESIS: Aim of our study was to
assess if NOD2/CARD15 variants have a role in the etiology or in the clinical
course of patients with ACU, either idiopathic or associated with other
inflammatory diseases. TESTING THE HYPOTHESIS: We consecutively enrolled 25
patients (19 pediatric and 6 adults) affected with ACU. For each patient medical
history was reviewed and clinical data were recorded. Allelic and genotypic
frequencies of NOD2/CARD15 variations were calculated in patients and matched
with those of 25 healthy controls. The statistical analysis was performed.
Fifteen patients showed the polymorphism P268S/SNP5 (SNP rs2066842) as
heterozygous carriers while two patients were homozygous for the same
polymorphism; one patient carried also the variant c647 18-16 TCT on intron 3,
not previously reported in the literature. Statistical analysis for NOD2/CARD15
genotyping showed significant differences between patients and controls for
allelic frequencies (p = 0.04, OR: 4.03, 95 %; CI = 1.2-13.5) but not for
genotypic frequencies. We could not identify a significant phenotype-genotype
correlation. IMPLICATIONS OF THE HYPOTHESIS: In our cohort of Italian patients,
the NOD2/CARD15 common variant P268S/SNP5 could potentially be significantly
associated with ACU.
PMID- 26438150
TI - Neuroprotection Against Diisopropylfluorophosphate in Acute Hippocampal Slices.
AB - Diisopropylfluorophosphate (DFP) is an irreversible inhibitor of acetylcholine
esterase and a surrogate of the organophosphorus (OP) nerve agent sarin. The
neurotoxicity of DFP was assessed as a reduction of population spike (PS) area
elicited by synaptic stimulation in acute hippocampal slices. Two classical
antidotes, atropine, and pralidoxime, and two novel antidotes, 4R-cembranotriene
diol (4R) and a caspase nine inhibitor, were tested. Atropine, pralidoxime, and
4R significantly protected when applied 30 min after DFP. The caspase inhibitor
was neuroprotective when applied 5-10 min before or after DFP, suggesting that
early synaptic apoptosis is responsible for the loss of PSs. It is likely that
apoptosis starts at the synapses and, if antidotes are not applied, descends to
the cell bodies, causing death. The acute slice is a reliable tool for
mechanistic studies, and the assessment of neurotoxicity and neuroprotection with
PS areas is, in general, pharmacologically congruent with in vivo results and
predicts the effect of drugs in vivo. 4R was first found to be neuroprotective in
slices and later we demonstrated that 4R is neuroprotective in vivo. The
mechanism of neurotoxicity of OPs is not well understood, and there is a need for
novel antidotes that could be discovered using acute slices.
PMID- 26438153
TI - Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific
Discordances between Immunohistochemistry and Sequencing.
AB - Although sequencing provides the gold standard for identifying colorectal
carcinoma with BRAF V600E mutation, immunohistochemistry (IHC) with the recently
developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise
as a more widely available and rapid method. However, we identified anecdotal
discordance between VE1 IHC and sequencing results and therefore analyzed VE1
staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole
tissue sections from 480 colorectal carcinomas (323 BRAF wild-type, 142 BRAF
V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results
with melanomas and papillary thyroid carcinomas (PTC). With the Bond method,
among 142 BRAF V600E-mutated colorectal carcinomas, 77 (54%) had diffuse VE1
staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative.
Among 323 BRAF wild-type colorectal carcinomas, 196 (61%) were negative, but 127
(39%) had staining, including 7 with diffuse staining. When positivity was
defined as staining in >= 20% of tumor cells, VE1 IHC had sensitivity of 75% and
specificity of 93% for BRAF V600E mutation. With the Ventana method, among 57
BRAF V600E-mutated colorectal carcinomas, 36 (63%) had diffuse VE1 staining,
whereas 6 (11%) had no or weak (<20% of tumor cells) staining. Among 33 BRAF wild
type colorectal carcinomas, 16 (48%) had no or weak staining, whereas 15 (45%)
had heterogeneous staining. In contrast with colorectal carcinoma, Bond and
Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing
results. We conclude that VE1 IHC produces suboptimal results in colorectal
carcinoma and should not be used to guide patient management.
PMID- 26438152
TI - Functional analyses of ATM, ATR and Fanconi anemia proteins in lung carcinoma :
ATM, ATR and FA in lung carcinoma.
AB - BACKGROUND: ATM and ATR are kinases implicated in a myriad of DNA-damage
responses. ATM kinase inhibition radiosensitizes cells and selectively kills
cells with Fanconi anemia (FA) gene mutations. ATR kinase inhibition sensitizes
cells to agents that induce replication stress and selectively kills cells with
ATM and TP53 mutations. ATM mutations and FANCF promoter-methylation are reported
in lung carcinomas. METHODS: We undertook functional analyses of ATM, ATR, Chk1
and FA proteins in lung cancer cell lines. We included Calu6 that is reported to
be FANCL-deficient. In addition, the cancer genome atlas (TCGA) database was
interrogated for alterations in: 1) ATM, MRE11A, RAD50 and NBN; 2) ATR, ATRIP and
TOPBP1; and 3) 15 FA genes. RESULTS: No defects in ATM, ATR or Chk1 kinase
activation, or FANCD2 monoubiquitination were identified in the lung cancer cell
lines examined, including Calu6, and major alterations in these pathways were not
identified in the TCGA database. Cell lines were radiosensitized by ATM kinase
inhibitor KU60019, but no cell killing by ATM kinase inhibitor alone was
observed. While no synergy between gemcitabine or carboplatin and ATR kinase
inhibitor ETP-46464 was observed, synergy between gemcitabine and Chk1 kinase
inhibitor UCN-01 was observed in 54 T, 201 T and H460, and synergy between
carboplatin and Chk1 kinase inhibitor was identified in 201 T and 239 T. No
interactions between ATM, ATR and FA activation were observed by either ATM or
ATR kinase inhibition in the lung cancer cell lines. CONCLUSIONS: Analyses of ATM
serine 1981 and Chk1 serine 345 phosphorylation, and FANCD2 monoubiquitination
revealed that ATM and ATR kinase activation and FA pathway signaling are intact
in the lung cancer cell lines examined. As such, these posttranslational
modifications may have utility as biomarkers for the integrity of DNA damage
signaling pathways in lung cancer. Different sensitization profiles between
gemcitabine and carboplatin and ATR kinase inhibitor ETP-46464 and Chk1 kinase
inhibitor UCN-01 were observed and this should be considered in the rationale for
Phase I clinical trial design with ATR kinase inhibitors.
PMID- 26438154
TI - BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic
Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose
Homeostasis.
AB - Inhibition of the IGF1R, INSRA, and INSRB receptor tyrosine kinases represents an
attractive approach of pharmacologic intervention in cancer, owing to the roles
of the IGF1R and INSRA in promoting cell proliferation and survival. However, the
central role of the INSRB isoform in glucose homeostasis suggests that prolonged
inhibition of this kinase could result in metabolic toxicity. We describe here
the profile of the novel compound BI 885578, a potent and selective ATP
competitive IGF1R/INSR tyrosine kinase inhibitor distinguished by rapid
intestinal absorption and a short in vivo half-life as a result of rapid
metabolic clearance. BI 885578, administered daily per os, displayed an
acceptable tolerability profile in mice at doses that significantly reduced the
growth of xenografted human GEO and CL-14 colon carcinoma tumors. We found that
treatment with BI 885578 is accompanied by increases in circulating glucose and
insulin levels, which in turn leads to compensatory hyperphosphorylation of
muscle INSRs and subsequent normalization of blood glucose within a few hours. In
contrast, the normalization of IGF1R and INSR phosphorylation in GEO tumors
occurs at a much slower rate. In accordance with this, BI 885578 led to a
prolonged inhibition of cell proliferation and induction of apoptosis in GEO
tumors. We propose that the remarkable therapeutic window observed for BI 885578
is achieved by virtue of the distinctive pharmacokinetic properties of the
compound, capitalizing on the physiologic mechanisms of glucose homeostasis and
differential levels of IGF1R and INSR expression in tumors and normal tissues.
PMID- 26438155
TI - Systemic Administration and Targeted Radiosensitization via Chemically Synthetic
Aptamer-siRNA Chimeras in Human Tumor Xenografts.
AB - Radiation therapy is a highly effective tool for treating all stages of prostate
cancer, from curative approaches in localized disease to palliative care and
enhanced survival for patients with distant bone metastases. The therapeutic
index of these approaches may be enhanced with targeted radiation-sensitizing
agents. Aptamers are promising nucleic acid delivery agents for short interfering
RNAs (siRNA) and short hairpin RNAs (shRNA). We have previously developed a
radiation-sensitizing RNA aptamer-shRNA chimera that selectively delivers DNA-PK
targeting shRNAs to prostate-specific membrane antigen (PSMA) positive cells in
the absence of transfection reagents. Although these chimera are effective, their
synthesis requires in vitro transcription and their evaluation was limited to
intratumoral administration. Here, we have developed a second-generation aptamer
siRNA chimera that can be assembled through the annealing of three separate
chemically synthesized components. The resulting chimera knocked down DNA-PK in
PSMA-positive prostate cancer cells, without the need of additional transfection
reagents, and enhanced the efficacy of radiation-mediated cell death. Following
intravenous injection, the chimera effectively knocked down DNA-PK in established
subcutaneous PSMA-positive tumors. Systemic treatment with these radiation
sensitizing agents selectively enhanced the potency of external beam radiation
therapy for established PSMA-positive tumors.
PMID- 26438156
TI - A TORC2-Akt Feed-Forward Topology Underlies HER3 Resiliency in HER2-Amplified
Cancers.
AB - The requisite role of HER3 in HER2-amplified cancers is beyond what would be
expected as a dimerization partner or effector substrate and it exhibits a
substantial degree of resiliency that mitigates the effects of HER2-inhibitor
therapies. To better understand the roots of this resiliency, we conducted an in
depth chemical-genetic interrogation of the signaling network downstream of HER3.
A unique attribute of these tumors is the deregulation of TORC2. The upstream
signals that ordinarily maintain TORC2 signaling are lost in these tumors, and
instead TORC2 is driven by Akt. We find that in these cancers HER3 functions as a
buffering arm of an Akt-TORC2 feed-forward loop that functions as a self
perpetuating module. This network topology alters the role of HER3 from a
conditionally engaged ligand-driven upstream physiologic signaling input to an
essential component of a concentric signaling throughput highly competent at
preservation of homeostasis. The competence of this signaling topology is evident
in its response to perturbation at any of its nodes. Thus, a critical
pathophysiologic event in the evolution of HER2-amplified cancers is the loss of
the input signals that normally drive TORC2 signaling, repositioning it under Akt
dependency, and fundamentally altering the role of HER3. This reprogramming of
the downstream network topology is a key aspect in the pathogenesis of HER2
amplified cancers and constitutes a formidable barrier in the targeted therapy of
these cancers.
PMID- 26438158
TI - PARP Inhibitors Sensitize Ewing Sarcoma Cells to Temozolomide-Induced Apoptosis
via the Mitochondrial Pathway.
AB - Ewing sarcoma has recently been reported to be sensitive to poly(ADP)-ribose
polymerase (PARP) inhibitors. Searching for synergistic drug combinations, we
tested several PARP inhibitors (talazoparib, niraparib, olaparib, veliparib)
together with chemotherapeutics. Here, we report that PARP inhibitors synergize
with temozolomide (TMZ) or SN-38 to induce apoptosis and also somewhat enhance
the cytotoxicity of doxorubicin, etoposide, or ifosfamide, whereas actinomycin D
and vincristine show little synergism. Furthermore, triple therapy of olaparib,
TMZ, and SN-38 is significantly more effective compared with double or
monotherapy. Mechanistic studies revealed that the mitochondrial pathway of
apoptosis plays a critical role in mediating the synergy of PARP inhibition and
TMZ. We show that subsequent to DNA damage-imposed checkpoint activation and G2
cell-cycle arrest, olaparib/TMZ cotreatment causes downregulation of the
antiapoptotic protein MCL-1, followed by activation of the proapoptotic proteins
BAX and BAK, mitochondrial outer membrane permeabilization (MOMP), activation of
caspases, and caspase-dependent cell death. Overexpression of a nondegradable MCL
1 mutant or BCL-2, knockdown of NOXA or BAX and BAK, or the caspase inhibitor N
benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) all significantly
reduce olaparib/TMZ-mediated apoptosis. These findings emphasize the role of PARP
inhibitors for chemosensitization of Ewing sarcoma with important implications
for further (pre)clinical studies.
PMID- 26438157
TI - Efficacy of PARP Inhibitor Rucaparib in Orthotopic Glioblastoma Xenografts Is
Limited by Ineffective Drug Penetration into the Central Nervous System.
AB - PARP inhibition can enhance the efficacy of temozolomide and prolong survival in
orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate
the combination of the PARP inhibitor rucaparib with temozolomide and to
correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient
derived GBM xenograft models. The combination of rucaparib with temozolomide was
highly effective in vitro in short-term explant cultures derived from GBM12, and,
similarly, the combination of rucaparib and temozolomide (dosed for 5 days every
28 days for 3 cycles) significantly prolonged the time to tumor regrowth by 40%
in heterotopic xenografts. In contrast, the addition of rucaparib had no impact
on the efficacy of temozolomide in GBM12 or GBM39 orthotopic models. Using Madin
Darby canine kidney (MDCK) II cells stably expressing murine BCRP1 or human MDR1,
cell accumulation studies demonstrated that rucaparib is transported by both
transporters. Consistent with the influence of these efflux pumps on central
nervous system drug distribution, Mdr1a/b(-/-)Bcrp1(-/-) knockout mice had a
significantly higher brain to plasma ratio for rucaparib (1.61 +/- 0.25) than
wild-type mice (0.11 +/- 0.08). A pharmacokinetic and pharmacodynamic evaluation
after a single dose confirmed limited accumulation of rucaparib in the brain is
associated with substantial residual PARP enzymatic activity. Similarly, matrix
assisted laser desorption/ionization mass spectrometric imaging demonstrated
significantly enhanced accumulation of drug in flank tumor compared with normal
brain or orthotopic tumors. Collectively, these results suggest that limited drug
delivery into brain tumors may significantly limit the efficacy of rucaparib
combined with temozolomide in GBM.
PMID- 26438159
TI - ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR
Inhibitor.
AB - Drugs that target specific gene alterations have proven beneficial in the
treatment of cancer. Because cancer cells have multiple resistance mechanisms, it
is important to understand the downstream pathways of the target genes and
monitor the pharmacodynamic markers associated with therapeutic efficacy. We
performed a transcriptome analysis to characterize the response of various cancer
cell lines to a selective fibroblast growth factor receptor (FGFR) inhibitor
(CH5183284/Debio 1347), a mitogen-activated protein kinase kinase (MEK)
inhibitor, or a phosphoinositide 3-kinase (PI3K) inhibitor. FGFR and MEK
inhibition produced similar expression patterns, and the extracellular signal
regulated kinase (ERK) gene signature was altered in several FGFR inhibitor
sensitive cell lines. Consistent with these findings, CH5183284/Debio 1347
suppressed phospho-ERK in every tested FGFR inhibitor-sensitive cell line.
Because the mitogen-activated protein kinase (MAPK) pathway functions downstream
of FGFR, we searched for a pharmacodynamic marker of FGFR inhibitor efficacy in a
collection of cell lines with the ERK signature and identified dual-specificity
phosphatase 6 (DUSP6) as a candidate marker. Although a MEK inhibitor suppressed
the MAPK pathway, most FGFR inhibitor-sensitive cell lines are insensitive to MEK
inhibitors and we found potent feedback activation of several pathways via FGFR.
We therefore suggest that FGFR inhibitors exert their effect by suppressing ERK
signaling without feedback activation. In addition, DUSP6 may be a
pharmacodynamic marker of FGFR inhibitor efficacy in FGFR-addicted cancers.
PMID- 26438160
TI - Longitudinal assessment of fractional anisotropy alterations caused by simian
immunodeficiency virus infection: a preliminary diffusion tensor imaging study.
AB - Previous diffusion tensor imaging (DTI) studies found that human immunodeficiency
virus (HIV) infection led to white matter (WM) microstructure degeneration. Most
of the DTI studies were cross-sectional and thus merely investigated only one
specific point in the disease. In order to systematically study the WM
impairments caused by HIV infection, more longitudinal studies are needed.
However, longitudinal studies on HIV patients are very difficult to conduct. To
address this question, we employed the simian immunodeficiency virus (SIV)
infected rhesus monkeys model to carry out a longitudinal DTI study. We aimed to
longitudinally access the WM abnormalities of SIV-infected rhesus monkeys by
studying the fractional anisotropy (FA) alterations with Tract Based Spatial
Statistic (TBSS) analysis. Four rhesus monkeys inoculated intravenously with
SIVmac239 were utilized in the study. DTI scans and peripheral blood CD4(+) and
CD8(+) T cell counts were acquired prior to virus inoculation (as the baseline)
and in the 12th and 24th week postvirus inoculation. Significant FA alterations
were found in the two areas of the inferotemporal regions (iTE), respectively
located in the ventral subregion of posterior iTE (iTEpv) and the dorsal
subregion of iTE (iTEpd). The decreased FA values in iTEpd were found
significantly negatively correlated with the elevated peripheral blood
CD4(+)/CD8(+) ratios. It might suggest that WM in iTEpd was still impaired even
though the immune dysfunction alleviated temporally.
PMID- 26438161
TI - Cytokine inhibition in chronic fatigue syndrome patients: study protocol for a
randomized controlled trial.
AB - BACKGROUND: Chronic fatigue syndrome (CFS) is a medically unexplained syndrome
for which no somatic or pharmacological treatment has been proven effective.
Dysfunction of the cytokine network has been suspected to play a role in the
pathophysiology of CFS. The disturbances of the cytokine network detected in CFS
patients are highly variable, in part due to the lack of adequate controls in
many studies. Furthermore, all studies have been performed on peripheral venous
blood of patients. As cytokines mainly act in tissues, for example, the brain,
the information that can be derived from peripheral blood cells is limited. The
information regarding the possible role of cytokines in the pathophysiology could
come from intervention studies in which the activities of relevant cytokines are
reduced, for example, reducing interleukin-1, interleukin-6 or tumor necrosis
factor. In this study, the clinical usefulness of anakinra, an IL-1 antagonist,
will be assessed in patients with CFS. METHODS/DESIGN: A randomized placebo
controlled, double-blind trial will be conducted. Fifty adult female patients
meeting the Centers for Disease Control (CDC) criteria for CFS and without
psychiatric co-morbidity will be included. After inclusion, patients will be
randomized between treatment with anakinra (recombinant human interleukin-1
receptor antagonist) or placebo. Each group will be treated for 4 weeks. Outcome
measures will be assessed at baseline, after 4 weeks of intervention, and 6
months after baseline assessment. The primary outcome measure will be fatigue
severity at 4 weeks, measured with the validated Checklist of Individual Strength
(CIS). Secondary outcome measures are functional impairment, physical and social
functioning, psychological distress, pain severity, presence of accompanying
symptoms, and cytokine and cortisol concentrations. DISCUSSION: This is the first
randomized placebo-controlled trial that will evaluate the effect of interference
with IL-1 on the experience of fatigue in patients with CFS. The results of this
study may expand treatment options for patients with CFS, for whom graded
exercise therapy and cognitive behavioral therapy are the only evidence-based
interventions that exist at this moment. TRIAL REGISTRATION: Clinicaltrials.gov:
NCT02108210 . Clinicaltrials.gov registration date: 8 April 2014. EudraCT: 2013
005466-19.
PMID- 26438162
TI - Enhancement of 3-hydroxypropionic acid production from glycerol by using a
metabolic toggle switch.
AB - BACKGROUND: 3-hydroxypropionic acid (3-HP) is an important platform for the
production of C3 chemicals, including acrylic acid, methyl acrylate, and
acrylamide. Microbial production of 3-HP is mainly due to glycerol metabolism. In
this study, in order to improve microbial 3-HP production, we applied a metabolic
toggle switch for controlling the glycerol metabolism to redirect the excess
metabolic flux of central metabolic pathway toward an exogenous 3-HP producing
pathway in Escherichia coli. RESULTS: The metabolic toggle switch enables
conditional repression of the expression of a target gene during the
fermentation. We individually performed conditional repression of glpK, tpiA, and
gapA, which are involved in glycerol metabolism. The conditional repression of
glpK and tpiA was not effective for 3-HP production under our experimental
conditions. However, gapA conditional repression contributed to improve 3-HP
production (titer, 54.2 +/- 1.5 mM; yield, 32.1 +/- 1.3 %) compared with that for
the wild type strain. Additional deletion of endogenous yqhD, which is
responsible for the production of a major byproduct, 1,3-propandiol, further
increased 3-HP production (titer, 67.3 +/- 2.1 mM; yield, 51.5 +/- 3.2 %). The
titer and yield were 80 and 94 % higher than those of the wild type strain,
respectively. The obtained 3-HP yield from glycerol is comparable with the
highest yield ever reported for microbial 3-HP production using glycerol as a
sole carbon source. The measurement of intracellular metabolites showed the
metabolic toggle switch successfully controlled the metabolic flux. CONCLUSION:
The conditional repression of gapA by using the metabolic toggle switch combined
with deletion of endogeneous yqhD increased 3-HP production approximately twofold
from glycerol. This result indicates the metabolic toggle switch can be applied
in various bio-production using diverse substrates.
PMID- 26438163
TI - Factors important in the choice of a medical career: a Finnish national study.
AB - BACKGROUND: Applying for medical school is the first and also one of the most
important career choices a physician makes. It is important to understand the
reasons behind this decision if we are to choose the best applicants for medical
schools and enable them to pursue satisfying careers. METHODS: Respondents to the
Finnish Junior Physician 88, Physician 1998 and Physician 2008 studies were
asked: "To what extent did the following factors influence your decision to apply
for medical school?" In 1998 and 2008 the respondents were also asked: "If you
were starting your studies now, would you start studying medicine?" and had to
answer "Yes" or "No". The odds ratios for the answer "No" were tested using
logistic regression models. RESULTS: "Interest in people" was the main motive for
starting to study medicine. "Good salary" and "Prestigious profession" were more
important motives for males and "Vocation" and "Interest in people" for females.
There were some significant changes in the motives for entering medicine in the
20-year period between studies. "Vocation" and "Wide range of professional
opportunities" as important motives for entering medicine predicted satisfaction
with the medical profession. DISCUSSION: Strong inner motivation may indicate the
ability to adapt to the demands of work as a physician. CONCLUSIONS: Medical
schools should try to select those applicants with the greatest vocational
inclination towards a medical career.
PMID- 26438164
TI - A single gene all3940 (Dps) overexpression in Anabaena sp. PCC 7120 confers
multiple abiotic stress tolerance via proteomic alterations.
AB - DNA-binding proteins (Dps) induced during starvation play an important role in
gene regulation and maintaining homeostasis in bacteria. The nitrogen-fixing
cyanobacterium, Anabaena PCC7120, has four genes annotated as coding for Dps;
however, the information on their physiological roles is limiting. One of the
genes coding for Dps, 'all3940' was found to be induced under different abiotic
stresses in Anabaena and upon overexpression enhanced the tolerance of Anabaena
to a multitude of stresses, which included salinity, heat, heavy metals,
pesticide, and nutrient starvation. On the other hand, mutation in the gene
resulted in decreased growth of Anabaena. The modulation in the levels of All3940
in Anabaena, achieved either by overexpression of the protein or mutation of the
gene, resulted in changes in the proteome, which correlated well with the
physiological changes observed. Proteins required for varied physiological
activities, such as photosynthesis, carbon-metabolism, oxidative stress
alleviation, exhibited change in protein profile upon modulation of All3940
levels in Anabaena. This suggested a direct or an indirect effect of All3940 on
the expression of the above stress-responsive proteins, thereby enhancing
tolerance in Anabaena PCC7120. Thus, All3940, though categorized as a Dps, is
possibly a general stress protein having a global role in regulating tolerance to
multitude of stresses in Anabaena.
PMID- 26438165
TI - MicroRNAs in the oriental fruit fly, Bactrocera dorsalis: extending Drosophilid
miRNA conservation to the Tephritidae.
AB - BACKGROUND: The oriental fruit fly, Bactrocera dorsalis, is an important plant
pest species in the family Tephritidae. It is a phytophagous species with broad
host range, and while not established in the mainland United States, is a species
of great concern for introduction. Despite the vast amount of information
available from the closely related model organism Drosophila melanogaster,
information at the genome and transcriptome level is still very limited for this
species. Small RNAs act as regulatory molecules capable of determining transcript
levels in the cells. The most studied small RNAs are micro RNAs, which may impact
as much as 30 % of all protein coding genes in animals. RESULTS: We have
sequenced small RNAs (sRNAs) from the Tephritid fruit fly, B. dorsalis (oriental
fruit fly), specifically sRNAs corresponding to the 17 to 28 nucleotides long
fraction of total RNA. Sequencing yielded more than 16 million reads in total.
Seventy five miRNAs orthologous to known miRNAs were identified, as well as five
additional novel miRNAs that might be specific to the genera, or to the Tephritid
family. We constructed a gene expression profile for the identified miRNAs, and
used comparative analysis with D. melanogaster to support our expression data. In
addition, several miRNA clusters were identified in the genome that show
conservancy with D. melanogaster. Potential targets for the identified miRNAs
were also searched. CONCLUSIONS: The data presented here adds to our growing pool
of information concerning the genome structure and characteristics of true fruit
flies. It provides a basis for comparative studies with other Dipteran and within
Tephritid species, and can be used for applied research such as in the
development of new control strategies based on gene silencing and transgenesis.
PMID- 26438166
TI - Morbidity associated with anterior iliac crest bone graft harvesting in children
undergoing orthopaedic surgery: a prospective review.
AB - PURPOSE: Autologous iliac crest bone grafting is an integral part of many
orthopaedic surgical procedures. Several studies have documented morbidity and
prolonged pain following iliac crest bone graft harvesting in adults; however, in
children there is a paucity of information. The purpose of the present study was
to quantify the degree of pain and morbidity associated with anterior iliac crest
graft harvesting in children undergoing non-spinal orthopaedic surgery. METHODS:
Patients were prospectively enrolled prior to orthopaedic surgery. A patient self
reported visual analogue score was used to record pain at specified time points
following surgery. In addition, the patients were reviewed at 2 and 6 weeks, 3
months and 1 year after surgery to record any complications. RESULTS: Data was
collected on 33 patients (34 graft sites). Only one patient (2.94 %) had a
complication, namely an injury to the lateral femoral cutaneous nerve. This
resolved 3 months after surgery. 89 % of patients had no pain at the iliac crest
graft harvest site 3 months after surgery. The three patients who had pain at 3
months had visual analogue scores of 1.0, 1.1 and 1.3, respectively. CONCLUSION:
This series reveals a very low complication rate and minimal iliac crest graft
harvest site pain in children undergoing non-spinal orthopaedic surgery. In
addition, the pain experienced is short-lived.
PMID- 26438168
TI - Topical issue: multimodality imaging in atherosclerosis.
PMID- 26438167
TI - Mapping and direct valuation: do they give equivalent EQ-5D-5L index scores?
AB - OBJECTIVE: Utility values of health states defined by health-related quality of
life instruments can be derived from either direct valuation ('valuation
derived') or mapping ('mapping-derived'). This study aimed to compare the utility
based EQ-5D-5L index scores derived from the two approaches as a means to
validating the mapping function developed by van Hout et al for the EQ-5D-5L
instrument. METHODS: This was an observational study of 269 breast cancer
patients whose EQ-5D-5L index scores were derived from both methods. For
comparing discriminatory ability and responsiveness to change, multivariable
regression models were used to estimate the effect sizes of various health
indicators on the index scores. Agreement and test-retest reliability were
examined using intraclass correlation coefficient (ICC). Whenever appropriate,
the 90% confidence intervals (90% CI) were compared to predefined equivalence
margins. RESULTS: The mean difference in and ICC between the valuation- and
mapping-derived EQ-5D-5L index scores were 0.015 (90% CI = 0.006 to 0.024) and
0.915, respectively. Discriminatory ability and responsiveness of the two indices
were equivalent in 13 of 15 regression analyses. However, the mapping-derived
index score was lower than the valuation-derived index score in patients
experiencing extreme health problems, and the test-retest reliability of the
former was lower than the latter, for example, their ICCs differed by 0.121 (90%
CI = 0.051 to 0.198) in patients who reported no change in performance status in
the follow-up survey. CONCLUSION: This study provided the first evidence
supporting the validity of the mapping function for converting EQ-5D-5L profile
data into a utility-based index score.
PMID- 26438169
TI - Posterior decompression and stabilisation of a spondylodiscitis L4/5.
PMID- 26438170
TI - Percutaneous posterior stabilisation of L1 to L5 with microsurgical decompression
of L3/4, and percutaneous L3 biopsy, in a spinal metastasis.
PMID- 26438171
TI - Posterior stabilization of the cervical spine with lateral mass screws.
PMID- 26438172
TI - Vertebral body replacement in the thoracolumbar spine via a mini-open,
thoracoscopically assisted transthoracic approach.
PMID- 26438173
TI - Is it possible to preserve lumbar lordosis after hybrid stabilization?
Preliminary results of a novel rigid-dynamic stabilization system in degenerative
lumbar pathologies.
AB - PURPOSE OF THE STUDY: To evaluate the results of a novel rigid-dynamic
stabilization technique in lumbar degenerative segment diseases (DSD), expressly
pointing out the preservation of postoperative lumbar lordosis (LL). MATERIALS
AND METHODS: Forty-one patients with one level lumbar DSD and initial disc
degeneration at the adjacent level were treated. Circumferential lumbar
arthrodesis and posterior hybrid instrumentation were performed to preserve an
initial disc degeneration above the segment that has to be fused. Clinical and
spino-pelvic parameters were evaluated pre- and postoperatively. RESULTS: At 2
year follow-up, a significant improvement of clinical outcomes was reported. No
statistically significant difference was noted between postoperative and 2-year
follow-up in LL and in disc/vertebral body height ratio at the upper adjacent
fusion level. CONCLUSIONS: When properly selected, this technique leads to good
results. A proper LL should be achieved after any hybrid stabilization to
preserve the segment above the fusion.
PMID- 26438174
TI - Head repositioning accuracy in patients with neck pain and asymptomatic subjects:
concurrent validity, influence of motion speed, motion direction and target
distance.
AB - BACKGROUND: Cervicocephalic kinesthetic deficiencies have been demonstrated in
patients with chronic neck pain (NP). On the other hand, authors emphasized the
use of different motion speeds for assessing functional impairment of the
cervical spine. PURPOSE: The objectives of this study were (1) to investigate the
head repositioning accuracy in NP patients and control subjects and (2) to assess
the influence of target distance, motion speed, motion direction and pain.
MATERIALS AND METHODS: Seventy-one subjects (36 healthy subjects and 35 NP
patients; age 30-55 years) performed the head repositioning test (HRT) at two
different speeds for horizontal and vertical movements and at two different
distances. For each condition, six consecutive trials were sampled. RESULTS: The
study showed the validity and reproducibility of the HRT, confirming a
dysfunctional threshold of 4.5 degrees . Normative values of head repositioning
error up to 3.6 degrees and 7.1 degrees were identified for healthy and NP
subjects, respectively. A distance of 180 cm from the target and a natural motion
speed increased HRT accuracy. Repositioning after extension movement showed a
significantly larger error in both groups. Intensity, duration of pain as well as
pain level did not significantly alter head repositioning error. CONCLUSIONS: The
assessment of proprioceptive performance in healthy and NP subjects allowed the
validation of the HRT. The HRT is a simple, not expensive and fast test, easily
implementable in daily practice to assess and monitor treatment and evolution of
proprioceptive cervical deficits.
PMID- 26438175
TI - Variation of Stable Carbon and Nitrogen Isotopic Composition of PM10 at Urban
Sites of Indo Gangetic Plain (IGP) of India.
AB - This paper presents the variation of elemental concentrations of total carbon
(TC), total nitrogen (TN) and isotopic ratios of delta13C and delta15N along with
delta13OC and OC of PM10 mass over Delhi, Varanasi and Kolkata of the Indo
Gangetic Plain (IGP), India. For Delhi, the average concentrations of TC and TN
of PM10 were 53.0+/-33.6 and 14.9+/-10.8 ug m(-3), whereas delta13C and delta15N
of PM10 were -25.5+/-0.5 and 9.6+/-2.80/00, respectively. For Varanasi, the
average values of delta13C and delta15N of PM10 were -25.4+/-0.8 and 6.8+/
2.40/00, respectively. For Kolkata, TC and TN values for PM10 ranged from 9.1
98.2 to 1.4-25.9 ug m(-3), respectively with average values of 32.6+/-24.9 and
9.3+/-8.2 ug m(-3), respectively. The average concentrations of delta13C and
delta15N were -26.0+/-0.4 and 7.4+/-2.70/00, respectively over Kolkata with
ranges of -26.6 to -24.90/00 and 2.8+/-11.50/00, respectively. The isotopic
analysis revealed that biomass burning, vehicular emission and secondary
inorganic aerosols were likely sources of PM10 mass over IGP, India.
PMID- 26438176
TI - Magnetic Graphene-Dispersive Solid-Phase Extraction for Preconcentration and
Determination of Lead and Cadmium in Dairy Products and Water Samples.
AB - A magnetic-dispersive solid-phase extraction (MDSPE) was used for precocentration
of Pb(II) and Cd(II) in milk, yoghurt and water samples. An appropriate amount of
suspension containing the magnetic graphene and Triton X-114 was injected rapidly
into the aqueous sample by a syringe. Triton X-114 was used to achieve stable
suspension of graphene in solution. The structure of the resulting products was
confirmed by Fourier transform infrared (FT-IR) spectra, X-ray diffraction (XRD)
spectrometry. The effects of various parameters were studied. A detection limit
of 0.16 and 0.50 ug L(-1) for Cd(II) and Pb(II) was obtained, respectively. The
relative standard deviations (RSDs, n = 10) of 50 ug L(-1) of Pb and Cd were 3.3
% and 2.1 %, respectively. The results indicated that the present method can be
reliably used for determination of Pb(II) and Cd(II) in dairy products and water
samples with good recoveries.
PMID- 26438177
TI - Mercury Inhibits Soil Enzyme Activity in a Lower Concentration than the Guideline
Value.
AB - Three soil types - neutral, alkaline and acidic were experimentally contaminated
with nine different concentrations of inorganic mercury (0, 5, 10, 50, 100, 150,
200, 250, 300 mg/kg) to derive effective concentrations of mercury that exert
toxicity on soil quality. Bioavailability of mercury in terms of water solubility
was lower in acidic soil with higher organic carbon. Dehydrogenase enzyme
activity and nitrification rate were chosen as indicators to assess soil quality.
Inorganic mercury significantly inhibited (p < 0.001) microbial activities in the
soils. The critical mercury contents (EC10) were found to be less than the
available safe limits for inorganic mercury which demonstrated inadequacy of
existing guideline values.
PMID- 26438178
TI - Temporal evolution of brain cancer incidence in the municipalities of Navarre and
the Basque Country, Spain.
AB - BACKGROUND: Brain cancer incidence rates in Spain are below the European's
average. However, there are two regions in the north of the country, Navarre and
the Basque Country, ranked among the European regions with the highest incidence
rates for both males and females. Our objective here was two-fold. Firstly, to
describe the temporal evolution of the geographical pattern of brain cancer
incidence in Navarre and the Basque Country, and secondly, to look for specific
high risk areas (municipalities) within these two regions in the study period
(1986-2008). METHODS: A mixed Poisson model with two levels of spatial effects is
used. The model also included two levels of spatial effects (municipalities and
local health areas). Model fitting was carried out using penalized quasi
likelihood. High risk regions were detected using upper one-sided confidence
intervals. RESULTS: Results revealed a group of high risk areas surrounding
Pamplona, the capital city of Navarre, and a few municipalities with significant
high risks in the northern part of the region, specifically in the border between
Navarre and the Basque Country (Gipuzkoa). The global temporal trend was found to
be increasing. Differences were also observed among specific risk evolutions in
certain municipalities. CONCLUSIONS: Brain cancer incidence in Navarre and the
Basque Country (Spain) is still increasing with time. The number of high risk
areas within those two regions is also increasing. Our study highlights the need
of continuous surveillance of this cancer in the areas of high risk. However, due
to the low percentage of cases explained by the known risk factors, primary
prevention should be applied as a general recommendation in these populations.
PMID- 26438179
TI - Effect-site concentration of propofol required for LMA-SupremeTM insertion with
and without remifentanil: a randomized controlled trial.
AB - BACKGROUND: A new supraglottic device, the LMA-SupremeTM, has recently become
available for clinical use. Information on anaesthetic and co-adjuvant
requirements for insertion of the LMA-SupremeTM is limited. The present study
aimed to evaluate the optimal effect-site concentration of propofol in 50 %
(EC50) of adults necessary for successful insertion of the LMA-SupremeTM and to
examine remifentanil's effect on propofol requirements. METHODS: Fifty-eight
elective patients (aged 18-60 years; ASA (American Society Anaesthesiologists)
physical status classification I and II) scheduled for day surgery were randomly
assigned to one of two groups: propofol with saline or propofol with
remifentanil. Anaesthesia was induced by target-controlled infusion according to
predetermined effect-site concentrations of propofol and remifentanil (5 ng.mL(
1)). The EC50 was calculated using Dixon's up-and-down method. Ten minutes
following drug administration, LMA-SupremeTM insertion was attempted without the
use of muscle relaxant drugs. RESULTS: In the propofol + saline group, the EC50
of propofol required for LMA-SupremeTM insertion was 6.32 +/- 0.67 MUg.mL(-1) (95
% CI, 5.69-6.94 MUg.mL(-1)). With the addition of remifentanil at an effect-site
concentration of 5 ng.mL(-1), the EC50 of propofol required for LMA-SupremeTM
insertion was 2.50 +/- 0.80 MUg.mL(-1) (95 % CI, 1.82-3.17 MUg.mL(-1); p <
0.0001). CONCLUSIONS: The propofol requirement for smooth insertion of the LMA
SupremeTM was 60 % less when remifentanil (5 ng.mL(-1)) was co-administered.
CLINICAL TRIAL REGISTRATION: Identified as NCT01974648 at www.clinicaltrials.gov
.
PMID- 26438180
TI - Role of glial 14-3-3 gamma protein in autoimmune demyelination.
AB - BACKGROUND: The family of 14-3-3 proteins plays an important role in the
regulation of cell survival and death. Here, we investigate the role of the 14-3
3 gamma (14-3-3 gamma) subunit for glial responses in autoimmune demyelination.
METHODS: Expression of 14-3-3 gamma in glial cell culture was investigated by
reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry.
14-3-3 gamma knockout mice were subjected to murine myelin oligodendrocyte
induced experimental autoimmune encephalomyelitis (MOG-EAE), an animal model
mimicking inflammatory features and neurodegenerative aspects of multiple
sclerosis (MS). RESULTS: Expression studies in cell culture confined expression
of 14-3-3 gamma to both, oligodendrocytes (OL) and astrocytes. RT-PCR analysis
revealed an increased expression of 14-3-3 gamma mRNA in the spinal cord during
the late chronic phase of MOG-EAE. At that stage, EAE was more severe in 14-3-3
gamma knockout mice as compared to age- and gender-matched controls.
Histopathological analyses on day 56 post immunization (p.i.) revealed
significantly enhanced myelin damage as well as OL injury and secondary, an
increase in axonal injury and gliosis in 14-3-3 gamma -/- mice. At the same time,
deficiency in 14-3-3 gamma protein did not influence the immune response. Further
histological studies revealed an increased susceptibility towards apoptosis in 14
3-3 gamma-deficient OL in the inflamed spinal cord. CONCLUSION: These data argue
for a pivotal role of 14-3-3 gamma-mediated signalling pathways for OL protection
in neuroinflammation.
PMID- 26438181
TI - Folate-Conjugated pH-Responsive Nanocarrier Designed for Active Tumor Targeting
and Controlled Release of Gemcitabine.
AB - PURPOSE: The prime end of this study was to design a novel pH-sensitive as well
as a PEGylated dendritic nanocarrier for both controllable and traceable
gemcitabine delivery to cancerous cells. To accomplish this goal, we took
advantage of a hybrid of nanoparticles including: mesoporous silica, graphene
oxide and magnetite. METHODS: The nanocarrier was prepared in a multi-step
synthesis route. First, magnetite mesoporous silica was deposited on the graphene
oxide matrix. Then, polyamidoamine dendrimers (up to generation 1.5) with
pentaethylene hexamine end groups were grafted on the surface of the
nanoparticles. In order to enhance the biostability, and as the next step, the
nanocarrier was modified by polyethylene glycol. Finally, these particles were
functionalized by folic acid as tumor targeting agents. RESULTS: According to the
dynamic light scattering results, the hydrodynamic diameter of magnetic
mesoporous silica graphene oxide hybrid nanoparticle was 152 +/- 3 nm, while for
the supramolecular hybrid nanoparticles it was about 324 +/- 12 nm. Attained
through the adsorption branch, the average pore diameter of these nanoparticles
was 7.6 nm. Zeta potential test indicated -27.1 mV value for hybrid nanoparticles
and +7.35 mV for supramolecular hybrid nanoparticles. Besides, cytotoxicity assay
showed enhanced cytotoxicity of epidermoid carcinoma cell line A431 in the
presence of folate conjugated carriers. The maximum release occurred at the pH
5.5, because the dendritic structure was in the open state rather than compact
state. CONCLUSIONS: The enhanced cytotoxicity of the epidermoid carcinoma cell
line A431 in the presence of folate conjugated carriers, confirmed the improved
cancerous cells uptake. Also, the positive surface potential would be a good
property for the biological applications because the inherent negative-charged
surface of cell membranes facilitates the uptake of positive particles by
electrostatic interactions.
PMID- 26438182
TI - Comment on Roessler et al.: Short-term follow up after implantation of a cell
free collagen type I matrix for the treatment of large cartilage defects of the
knee.
PMID- 26438183
TI - "Fatigue meniscal tears": a description of the lesion and the results of
arthroscopic partial meniscectomy.
AB - PURPOSE: The purpose of this study was to describe the clinical outcomes of
partial meniscectomy in patients with "fatigue meniscal tear", which presents as
a non-traumatic tear with abrupt onset of symptoms of a radial tear in the
transition between the middle and posterior thirds of the meniscus. METHODS: We
prospectively followed 71 patients with "fatigue meniscal tear" (41 women and 30
men, mean age of 63 years, SD 6.9 years) recruited among 497 patients with
isolated medial meniscal lesions treated between January 2006 and June 2011.
Inclusion criteria were spontaneous abrupt onset knee pain, minor or no trauma,
no radiographic or MRI osteoarthritis, no bone oedema, pre-operative magnetic
resonance image of medial meniscus tear, and arthroscopic evaluation
demonstrating radial or vertical flap tear in the body to posterior horn junction
of the medial meniscus. We followed all patients for a minimum of two years and
reviewed their clinical symptoms, physical exam, functional outcome, and patient
satisfaction at last follow-up. RESULTS: The average follow-up was 4.2 years,
with a minimum follow-up of two years. Among the 71 patients, there were 59 (83.1
%) good or excellent results and 12 (16.9 %) poor results. These 12 patients
demanded further treatment because of persistent pain, with three of the patients
developing subchondral bone fracture. All patient complaints and poor outcomes
could be identified in the initial six months after surgery. There was no gender
difference in the subgroup analysis. CONCLUSION: Our findings indicate that
patients with "fatigue meniscal tear" benefit from arthroscopic partial
meniscectomy, with only 16.9 % reporting unfavourable results. LEVEL OF EVIDENCE:
IV, Cohort study or case series.
PMID- 26438185
TI - Attitudes and practice patterns for maintaining relative dose intensity of
chemotherapy in outpatient clinics: results of a Japanese web-based survey.
AB - BACKGROUND: This analysis was undertaken to evaluate the practice patterns of
Japanese physicians regarding curative-intent chemotherapy, especially in
outpatient settings, and to define factors negatively affecting the maintenance
of relative dose intensity (RDI). METHODS: We performed a web-based questionnaire
survey of Japanese physicians involved in malignant lymphoma chemotherapy (Group
ML) or in breast cancer chemotherapy (Group BC). The questionnaire inquired how
they manage low-risk febrile neutropenia (FN) caused by initial chemotherapy for
diffuse large B-cell lymphoma(DLBCL) or by adjuvant chemotherapy for breast
cancer in an outpatient setting. RESULTS: Valid responses were obtained from 185
physicians in Group ML and 160 in Group BC. In Group ML, 76 % (n = 141) of the
physicians were board-certified hematologists, while 82 % (n = 131) of the
physicians in Group BC were board-certified surgeons. A significantly higher
proportion of physicians in Group ML responded that "dose reduction is not
required for the subsequent course of chemotherapy after the first episode of FN"
than in Group BC (ML versus BC; 77 % versus 31 %; P < 0.001). Significantly
higher proportions of physicians in Group ML were more likely to prophylactically
administer antibiotics or granulocyte-colony stimulating factor (G-CSF; ML versus
BC; antibiotics: 36 % versus 26 %, P = 0.049; G-CSF: 25 % versus 16 %, P =
0.047). Eighty six percent (n = 159) of Group ML and 70 % (n = 112) of Group BC
responded that "emergency outpatient unit is open at all hours". CONCLUSIONS:
Japanese physicians are more likely to administer reduced doses of chemotherapy
to patients with breast cancer than to patients with malignant lymphoma.
Supportive infrastructures should be improved to ensure the provision of adequate
chemotherapy to all cancer patients.
PMID- 26438184
TI - Effects of Intermittent Fasting, Caloric Restriction, and Ramadan Intermittent
Fasting on Cognitive Performance at Rest and During Exercise in Adults.
AB - The aim of this review was to highlight the potent effects of intermittent
fasting on the cognitive performance of athletes at rest and during exercise.
Exercise interacts with dietary factors and has a positive effect on brain
functioning. Furthermore, physical activity and exercise can favorably influence
brain plasticity. Mounting evidence indicates that exercise, in combination with
diet, affects the management of energy metabolism and synaptic plasticity by
affecting molecular mechanisms through brain-derived neurotrophic factor, an
essential neurotrophin that acts at the interface of metabolism and plasticity.
The literature has also shown that certain aspects of physical performance and
mental health, such as coping and decision-making strategies, can be negatively
affected by daylight fasting. However, there are several types of intermittent
fasting. These include caloric restriction, which is distinct from fasting and
allows subjects to drink water ad libitum while consuming a very low-calorie food
intake. Another type is Ramadan intermittent fasting, which is a religious
practice of Islam, where healthy adult Muslims do not eat or drink during
daylight hours for 1 month. Other religious practices in Islam (Sunna) also
encourage Muslims to practice intermittent fasting outside the month of Ramadan.
Several cross-sectional and longitudinal studies have shown that intermittent
fasting has crucial effects on physical and intellectual performance by affecting
various aspects of bodily physiology and biochemistry that could be important for
athletic success. Moreover, recent findings revealed that immunological variables
are also involved in cognitive functioning and that intermittent fasting might
impact the relationship between cytokine expression in the brain and cognitive
deficits, including memory deficits.
PMID- 26438186
TI - A Mechanistic Neural Field Theory of How Anesthesia Suppresses Consciousness:
Synaptic Drive Dynamics, Bifurcations, Attractors, and Partial State
Equipartitioning.
AB - With the advances in biochemistry, molecular biology, and neurochemistry there
has been impressive progress in understanding the molecular properties of
anesthetic agents. However, there has been little focus on how the molecular
properties of anesthetic agents lead to the observed macroscopic property that
defines the anesthetic state, that is, lack of responsiveness to noxious stimuli.
In this paper, we use dynamical system theory to develop a mechanistic mean field
model for neural activity to study the abrupt transition from consciousness to
unconsciousness as the concentration of the anesthetic agent increases. The
proposed synaptic drive firing-rate model predicts the conscious-unconscious
transition as the applied anesthetic concentration increases, where excitatory
neural activity is characterized by a Poincare-Andronov-Hopf bifurcation with the
awake state transitioning to a stable limit cycle and then subsequently to an
asymptotically stable unconscious equilibrium state. Furthermore, we address the
more general question of synchronization and partial state equipartitioning of
neural activity without mean field assumptions. This is done by focusing on a
postulated subset of inhibitory neurons that are not themselves connected to
other inhibitory neurons. Finally, several numerical experiments are presented to
illustrate the different aspects of the proposed theory.
PMID- 26438187
TI - Spatial spillover effects of a community action programme targeting on-licensed
premises on violent assaults: evidence from a natural experiment.
AB - BACKGROUND: Spatial dependencies may influence the success of community action
strategies to prevent and reduce harmful alcohol use. This study examined the
effectiveness of a multicomponent Responsible Beverage Service (RBS) programme
targeting on-licensed premises on police-recorded assaults in Swedish
municipalities. It was expected that the implementation of the programme within
any given municipality had an indirect effect by reducing violent assaults in
adjacent municipalities. METHODS: This study was a natural experiment exploiting
the temporal and spatial variation in the implementation of the RBS programme to
predict change in the rate of violent assaults in all Swedish municipalities
during 1996-2009 (n=288; T=14; N=4 032). Yearly police-recorded violent assaults
per 100,000 inhabitants aged 15 and above committed on weekend nights were used
as a dependent variable. Programme fidelity was identified by means of survey
data. A semilogarithmic fixed-effects spatial panel regression model was used to
estimate the direct, indirect and total effects of the programme. RESULTS: The
direct, indirect and total effects were -1.8% (95% CI -4.4% to 0.8%), -5.8% (95%
CI -11.5% to -0.1%) and -7.6% (95% CI -13.2% to -2.2%), respectively. Averaged
over time and across all municipalities, implementing one additional programme
component in all municipalities will thus reduce violent assaults in one typical
municipality by nearly 8%. CONCLUSIONS: The indirect effect of the programme was
three times larger than its direct effect. Failing to account for such local
spillover effects can result in a considerable underestimation of the programme's
total impact and may lead to erroneous policy recommendations.
PMID- 26438188
TI - Ebola, jobs and economic activity in Liberia.
AB - BACKGROUND: The 2014 Ebola virus disease (EVD) outbreak in the neighbouring West
African countries of Guinea, Liberia and Sierra Leone represents the most
significant setback to the region's development in over a decade. This study
provides evidence on the extent to which economic activity declined and jobs
disappeared in Liberia during the outbreak. METHODS: To estimate how the level of
activity and number of jobs in a given set of firms changed during the outbreak,
we use a unique panel data set of registered firms surveyed by the business
development non-profit organisation, Building Markets. We also compare the change
in economic activity during the outbreak, across regions of the country that had
more versus fewer Ebola cases in a difference-in-differences approach. FINDINGS:
We find a large decrease in economic activity and jobs in all of Liberia during
the Ebola outbreak, and an especially large decline in Monrovia. Outside of
Monrovia, the restaurants, and food and beverages sectors have suffered the most
among the surveyed sectors, and in Monrovia, the construction and restaurant
sectors have shed the most employees, while the food and beverages sectors
experienced the largest drop in new contracts. We find little association between
the incidence of Ebola cases and declines in economic activity outside of
Monrovia. CONCLUSIONS: If the large decline in economic activity that occurred
during the Ebola outbreak persists, a focus on economic recovery may need to be
added to the efforts to rebuild and support the healthcare system in order for
Liberia to regain its footing.
PMID- 26438189
TI - The Candida albicans agglutinin-like sequence family of adhesins: functional
insights gained from structural analysis.
AB - Candida albicans colonizes many host sites suggesting its interaction with
diverse ligands. Candida albicans adhesion is mediated by a number of proteins
including those in the Als (agglutinin-like sequence) family, which have been
studied intensively. The recent solution of the Als binding domain structure
ended years of speculation regarding the molecular mechanism for Als adhesive
function. Als adhesins bind flexible C termini from a broad collection of
proteins, providing the basis for adhesion to various cell types and perhaps for
C. albicans broad tissue tropism. Understanding adhesive functions at the
molecular level will reveal the sequence of events in C. albicans pathogenesis,
from host recognition to complex interactions such as development of
polymicrobial biofilms or disseminated disease.
PMID- 26438190
TI - T-wave Right Slope Provides a New Angle in the Prediction of Drug-Induced
Ventricular Arrhythmias : Editorial to: "Electrocardiographic Predictors of
Torsadogenic Risk During Dofetilide or Sotalol Initiation: Utility of a Novel T
Wave Analysis Program" by Sugrue A. et al.
PMID- 26438191
TI - Cellular volume regulation by anoctamin 6: Ca2+, phospholipase A2 and
osmosensing.
AB - During cell swelling, Cl(-) channels are activated to lower intracellular Cl(-)
concentrations and to reduce cell volume, a process termed regulatory volume
decrease (RVD). We show that anoctamin 6 (ANO6; TMEM16F) produces volume
regulated anion currents and controls cell volume in four unrelated cell types.
Volume regulation is compromised in freshly isolated intestinal epithelial cells
from Ano6-/- mice and also in lymphocytes from a patient lacking expression of
ANO6. Ca(2+) influx is activated and thus ANO6 is stimulated during cell swelling
by local Ca(2+) increase probably in functional nanodomains near the plasma
membrane. This leads to stimulation of phospholipase A2 (PLA2) and generation of
plasma membrane lysophospholipids, which activates ANO6. Direct application of
lysophospholipids also activates an anion current that is inhibited by typical
ANO6 blocker. An increase in intracellular Ca(2+) supports activation of ANO6,
but is not required when PLA2 is fully activated, while re-addition of
arachidonic acid completely blocked ANO6. Moreover, ANO6 is activated by low
intracellular Cl(-) concentrations and may therefore operate as a cellular
osmosensor. High intracellular Cl(-) concentration inhibits ANO6 and activation
by PLA2. Taken together, ANO6 supports volume regulation and volume activation of
anion currents by action as a Cl(-) channel or by scrambling membrane
phospholipids. Thereby, it may support the function of LRRC8 proteins.
PMID- 26438192
TI - Unexpected dependence of RyR1 splice variant expression in human lower limb
muscles on fiber-type composition.
AB - The skeletal muscle ryanodine receptor Ca(2+) release channel (RyR1), essential
for excitation-contraction (EC) coupling, demonstrates a known developmentally
regulated alternative splicing in the ASI region. We now find unexpectedly that
the expression of the splice variants is closely related to fiber type in adult
human lower limb muscles. We examined the distribution of myosin heavy chain
isoforms and ASI splice variants in gluteus minimus, gluteus medius and vastus
medialis from patients aged 45 to 85 years. There was a strong positive
correlation between ASI(+)RyR1 and the percentage of type 2 fibers in the muscles
(r = 0.725), and a correspondingly strong negative correlation between the
percentages of ASI(+)RyR1 and percentage of type 1 fibers. When the type 2 fiber
data were separated into type 2X and type 2A, the correlation with ASI(+)RyR1 was
stronger in type 2X fibers (r = 0.781) than in type 2A fibers (r = 0.461). There
was no significant correlation between age and either fiber-type composition or
ASI(+)RyR1/ASI(-)RyR1 ratio. The results suggest that the reduced expression of
ASI(-)RyR1 during development may reflect a reduction in type 1 fibers during
development. Preferential expression of ASI(-) RyR1, having a higher gain of in
Ca(2+) release during EC coupling than ASI(+)RyR1, may compensate for the reduced
terminal cisternae volume, fewer junctional contacts and reduced charge movement
in type 1 fibers.
PMID- 26438193
TI - Parapatric distribution and sexual competition between two tick species,
Amblyomma variegatum and A. hebraeum (Acari, Ixodidae), in Mozambique.
AB - BACKGROUND: Amblyomma variegatum and A. hebraeum are two ticks of veterinary and
human health importance in south-east Africa. In Zimbabwe they occupy parapatric
(marginally overlapping and juxtaposed) distributions. Understanding the
mechanisms behind this parapatry is essential for predicting the spatio-temporal
dynamics of Amblyomma spp. and the impacts of associated diseases. It has been
hypothesized that exclusive competition between these species results from
competition at the levels of male signal reception (attraction-aggregation
attachment pheromones) or sexual competition for mates. This hypothesis predicts
that the parapatry described in Zimbabwe could also be present in other countries
in the region. METHODS: To explore this competitive exclusion hypothesis we
conducted field surveys at the two species' range limits in Mozambique to
identify areas of sympatry (overlapping areas) and to study potential
interactions (communicative and reproductive interference effects) in those
areas. At sympatric sites, hetero-specific mating pairs were collected and inter
specific attractiveness/repellent effects acting at long and short distances were
assessed by analyzing species co-occurrences on co-infested herds and co-infested
hosts. RESULTS: Co-occurrences of both species at sampling sites were infrequent
and localized in areas where both tick and host densities were low. At sympatric
sites, high percentages of individuals of both species shared attachment sites on
hosts and inter-specific mating rates were high. Although cross-mating rates were
not significantly different for A. variegatum and A. hebraeum females, attraction
towards hetero-specific males was greater for A. hebraeum females than for A.
variegatum females and we observed small asymmetrical repellent effects between
males at attachment sites. CONCLUSIONS: Our observations suggest near-symmetrical
reproductive interference between A. variegatum and A. hebraeum, despite between
species differences in the strength of reproductive isolation barriers acting at
the aggregation, fixation and partner contact levels. Theoretical models predict
that sexual competition coupled with hybrid inviability, greatly reduces the
probability of one species becoming established in an otherwise suitable location
when the other species is already established. This mechanism can explain why the
parapatric boundary in Mozambique has formed within an area of low tick densities
and relatively infrequent host-mediated dispersal events.
PMID- 26438194
TI - Cost of illness of the prostate cancer in Japan--a time-trend analysis and future
projections.
AB - BACKGROUND: The majority of patients with prostate cancer (International
Classification of Diseases, 10th edition, code C61) are elderly. With Japan's
rapidly society aging, both the prevalence and mortality of prostate cancer are
expected to increase in the future. The objective of this study was to estimate
and predict the cost of illness (COI) associated with prostate cancer in Japan.
METHODS: Using a COI method based on available data from government office
statistics, we estimated the COI for 2002, 2005, 2008, and 2011. We then
predicted the COI for 2014, 2017, and 2020 using fixed model estimation and
variable model estimation. With fixed model estimation, only estimated future
population was used as a variable. Variable model estimation considered the time
trend of health-related indicators in the past 15 years. We derived the COI from
the sum of direct and indirect costs (morbidity and mortality). RESULTS: We found
the predicted future COI of prostate cancer to be 354.7-378.3 billion yen in
2014, 370.8-421.0 billion yen in 2017, and 385.3-474.1 billion yen in 2020.
Regardless of the estimation model, we found that COI would increase compared
with the baseline year 2011 (307.3 billion yen). The direct costs for inpatient
and outpatient treatment, laboratory tests, and drugs accounted for 60-75% of the
COI of prostate cancer. CONCLUSIONS: The results of this study suggest that the
COI of prostate cancer in Japan has steadily increased and is expected to rise in
the future. Direct costs comprised the largest proportion of the COI and are
anticipated to continue expanding; this will result in increased burden on public
funds in Japan, where a universal public insurance system operates. These trends
differ from those with other forms of cancer.
PMID- 26438195
TI - Opportunities for involving men and families in chronic disease management: a
qualitative study from Chiapas, Mexico.
AB - BACKGROUND: A healthy lifestyle intervention was implemented in primary care
health centers in urban parts of Tuxtla Gutierrez, Chiapas, Mexico with an aim of
reducing cardiovascular disease risk for patients with type 2 diabetes and/or
hypertension. During implementation, research questions emerged. Considerably
fewer men participated in the intervention than women, and an opportunity was
identified to increase the reach of activities aimed at improving disease self
management through strategies involving family members. A qualitative study was
conducted to identify strategies to involve men and engage family members in
disease management and risk reduction. METHODS: Nine men with hypertension and/or
type 2 diabetes with limited to no participation in disease self-management and
health promotion activities, six families in which at least one family member had
a diagnosis of one or both conditions, and nine health care providers from four
different government health centers were recruited for the study. Participants
took part in semi-structured interviews. During interviews with families,
genograms and eco-maps were used to diagram family composition and structure, and
capture the nature of patients' relationships to the extended family and
community resources. Transcripts were coded and a general inductive analytic
approach was used to identify themes related to men's limited participation in
health promotion activities, family support and barriers to disease management,
and health care providers' recommendations. RESULTS: Participants reported
barriers to men's participation in chronic disease management and healthy
lifestyle education activities that can be grouped into two categories: internal
and external factors. Internal factors are those for which they are able to make
the decision on their own and external factors are those that are not related
solely to their decision to take part or not. Four primary aspects were
identified related to families' relationships with disease: different roles
within the family, types of support provided to patients, the opportunity to
prevent disease among family members without a diagnosis, and - in some cases -
lack of family support or stress-induced by other family members. There was an
overlap in recommended strategies for engaging men and family members in chronic
disease management activities. CONCLUSIONS: There is an opportunity to increase
the reach of interventions aimed at improving disease self-management by engaging
men and family members. The proposed strategies presented by patients, family
members, and providers have implications for health education and service
provision at primary care health centers and for future research.
PMID- 26438196
TI - [Should metal alloy discs be used for patch testing in suspected metal implant
intolerance reaction?].
AB - Intolerance reactions to metal implants may be caused by metal allergy. However,
prior to implantation, patch testing should not be done in a prophylactic
prophetic approach. Pre-implant patch testing should only be performed to verify
or exclude metal allergy in patients with a reported respective history. In the
case of implant-in particular arthroplasty-related complications like, for
example, pain, effusion, skin changes, reduced range of motion, or loosening,
orthopedic-surgical differential diagnostics should be performed first.
Allergological workup of suspected metal implant allergy should be done with the
DKG baseline series which contains nickel-, cobalt- and chromium-preparations.
Various studies assessing the usefulness of metal alloy discs for patch testing
proved that this approach does not give reliable information about metal allergy.
Positive patch test reactions to the discs cannot be assigned to a specific metal
within the disc alloy components. Furthermore, availability of such metal discs
might be an invitation to uncritical testing. Accordingly, due to lack of benefit
in comparison to patch testing with standardized metal salt preparations, we do
not recommend patch testing with metal alloy discs.
PMID- 26438197
TI - Frontotemporal epi- and subdural approach to a cavernous sinus tumor for
sphenobasal vein preservation--technical case report.
AB - In cavernous sinus (CS) surgery, venous complication may occur in some types of
venous drainage. The sphenobasal vein (SBV) drains from the superficial middle
cerebral vein (SMCV) to the pterygoid venous plexus at the temporal skull base. A
frontotemporal epi- and interdural approach (Dolenc approach), which is one of
the CS approaches, may damage the SBV's route. We report a case of intracavernous
trigeminal schwannoma that contained the SBV and discuss our modified surgical
procedure that combined epi- and subdural approaches to preserve the SBV. A 64
year-old man complained of right progressive oculomotor palsy and was referred to
our hospital for surgery. MR images revealed a hemorrhagic tumor in the right CS.
Three-dimensional venography revealed that the SMCV drained into the pterygoid
venous plexus via the SBV. After identifying the first branch of the trigeminal
nerve epidurally, we incised the dura linearly along the sylvian fissure and
entered the subdural space to visualize the SBV. The incision was continued to
the meningeal dura of the lateral wall of the CS along the superior margin of the
first branch of the trigeminal nerve, and the Parkinson's triangle was opened
from the subdural side. The tumor was grossly totally removed, and the SBV was
preserved. In conclusion, a frontotemporal epi- and subdural approach to the
intracavernous trigeminal schwannoma can effectively preserve the SBV.
PMID- 26438198
TI - Endoscopic submucosal dissection for early gastric cancer in elderly patients: a
meta-analysis.
AB - BACKGROUND: The effectiveness of endoscopic submucosal dissection (ESD) has been
increasingly reported. However, studies addressing the safety and application
value of ESD in elderly patients with early gastric cancer (EGC) were still
lacking. This meta-analysis was intended to evaluate the feasibility and safety
of ESD in elderly patients with EGC. METHODS: A systematic search was conducted
in PubMed, EBSCO, Cochrane Library, EMBASE, and Web of Science. Studies were
screened out if data of elderly and non-elderly gastric cancer patients were
reported separately. The qualities of included studies were assessed using
Newcastle-Ottawa Quality Assessment Scale. The pooled odd ratios (ORs) with 95 %
confidence intervals (CIs) were calculated. Statistical analysis was conducted
using the Review Manager 5.2 (Cochrane Collaboration, Oxford, UK). RESULTS: Nine
studies (eight in Japan, one in China), including a total of 30,100 lesions, met
the inclusion criteria. The "en bloc" and histological complete resection rates
of the elderly and non-elderly groups were similar [OR, 0.98, 95 % CI, 0.56 to
1.71; P = 0.93 and OR, 0.79, 95 % CI, 0.58 to 1.07; P = 0.13, respectively]. As
for procedure-related complications, similar perforation rates [OR, 1.19, 95 %
CI, 0.94 to 1.51; P = 0.15], and bleeding rates [OR, 1.13, 95 % CI, 0.83 to
1.56); P = 0.43] between the elderly and non-elderly groups were observed.
Whereas, the elderly patients had a higher procedure-related pneumonia rate
compared with non-elderly ones [OR, 2.18, 95 % CI, 1.55 to 3.08; P < 0.01].
CONCLUSIONS: The ESD procedure appears to be a safe technique in elderly patients
with EGC while appropriate approach should be taken to avoid procedure-related
pneumonia.
PMID- 26438200
TI - Influence of nutritional status on the therapeutic effect of infliximab in
patients with Crohn's disease.
AB - PURPOSE: Crohn's disease (CD) is a refractory inflammatory bowel disease of
unknown etiology, frequently complicated by malnutrition. It is thought that the
delayed wound healing associated with this malnutrition in CD patients might
adversely affect the therapeutic benefits of infliximab (IFX). Therefore, we
investigated the effects of nutritional status on IFX treatment. METHODS: We
assessed nutritional status and CD activity when IFX therapy was initiated and
following the third dose, 6 weeks later. Nutritional status was assessed using
the body mass index (BMI) and nutritional risk index (NRI), whereas CD activity
was assessed using the CD activity index (CDAI). RESULTS: All patients with a BMI
>= 18.5 kg/m(2) at the time of IFX therapy met the effective criteria for the
CDAI, and IFX treatment was considered responsive in these patients. Furthermore,
IFX treatment was responsive, with a high level of effectiveness, in all five
subjects (31.3 %) with NRI scores of 97.5 and above with no risk of malnutrition
(p = 0.037). CONCLUSIONS: Our results suggest that nutritional status does
influence the therapeutic effect of IFX in CD patients. The response rate to IFX
treatment thus could be improved by optimizing the nutritional status. We
recommend comprehensive nutritional assessment and intervention prior to IFX
treatment schedules.
PMID- 26438201
TI - Clinical implications of carotid artery intima media thickness assessment on
cardiovascular risk stratification in hyperlipidemic Korean adults with diabetes:
the ALTO study.
AB - BACKGROUND: The primary objective was to investigate prevalence of subclinical
atherosclerosis in Korean individuals with diabetes and hyperlipidemia.
Association of subclinical atherosclerosis with cardiovascular risk was assessed.
METHODS: Assessments of carotid artery intima media thickness (cIMT) and
atheromatous plaque were done using B-mode ultrasonography. Subclinical
atherosclerosis was diagnosed based on presence of plaque, and/or increased cIMT
versus mean cIMT reference values for Korean healthy controls. Atherosclerosis
risk factors were analyzed using United Kingdom Prospective Diabetes Study
(UKPDS) risk engine and Framingham Risk Score. RESULTS: In total, 355 patients
were included; increased mean cIMT was observed in 15.3 % of patients, 69 % had
>1 carotid artery plaque, and 72.7 % were diagnosed with subclinical
atherosclerosis. In total, 60 % of subjects were taking statins, with low-density
lipoprotein cholesterol level maintained ~80 mg/dL at enrollment. Carotid artery
measures were well correlated with UKPDS and Framingham risk scores. Prevalence
of subclinical atherosclerosis in the low risk group (<15 % 10-year UKPDS
predicted coronary heart disease risk) was 64.7 %; higher than predicted in
previous studies. In multivariate analysis, advanced age was a significant risk
factor for subclinical atherosclerosis in men and women, while increased waist
circumference and longer diabetes duration were independent predictors only in
women. CONCLUSION: Subclinical atherosclerosis is more prevalent among
individuals with both diabetes and hyperlipidemia than in diabetic patients
without additional cardiovascular risk factors. As conventional risk engines,
based on modifiable risk factors may underestimate cardiovascular risk, early non
invasive carotid artery imaging screening may be warranted for patients with
diabetes and hyperlipidemia, especially if they are elderly, have central obesity
or have long duration of diabetes. TRIAL REGISTRATION: www.clinicaltrials.gov
NCT01264263.
PMID- 26438202
TI - [Full thickness resection device (FTRD). Experience and outcome for benign
neoplasms of the rectum and colon].
AB - BACKGROUND: The diagnostic validity of a full-thickness resection is higher
compared to endoscopic mucosal resection (EMR) or endoscopic mucosal dissection
(ESD). Whereas transanal endoscopic microsurgery techniques (TEM, TAMIS) are
established therapeutic procedures in the rectum no established and safe
minimally invasive or endoscopic procedure exists in the colon. AIM: In this
study the novel endoscopic full thickness resection device (FTRD, Ovesco,
Germany) was investigated concerning success rates with histologically proven
full thickness resections, R0 status as well as patient and device safety for the
rectum and colon. METHOD: In the period from November 2014 to June 2015 full
thickness resections in the rectum and colon were performed with the FTRD in 20
patients. Data on technical success, R0 resection rate and histologically
confirmed full thickness resections were retrospectively analyzed. RESULTS: The
following indications were treated in the rectum (n = 11) and colon (n = 9): T1
carcinoma (n = 6) and neuroendocrine tumors (n = 2), untreated and nonlifting
adenomas (n = 3) and incomplete resection of adenomas with low and high grade
dysplasia (n = 9). The technical success rate was 75 %, 3 technical failures made
a conventional polypectomy necessary in 2 patients and in 1 patient an operative
resection of the duplicated intestinal wall had to be performed. The median
endoscopic follow-up time was 61.5 days (n = 10) and in 7 patients the clip had
dislodged at the first follow-up. A thermal perforation in one case of
conventional polypectomy gave rise to indications for a partial resection of the
colon. In one patient the lesion in the cecum could be reached but not treated
for technical reasons. The histological R0 rate was 80 %, whereas the full
thickness resection rate was 60 % (85.7 % in the colon and 54.6 % in the rectum).
In two patients with carcinoma and incomplete FTRD, surgical treatment was
performed. The median size of the resection specimen was 5 cm(2) (range 1.6-12.9
cm(2)). CONCLUSION: The results show that FTRD is a safe and effective
instrument for use in the lower gastrointestinal tract. Limitations of the FTRD
system concerning full thickness resection are scarring, fibrosis and thickness
of the intestinal wall, especially in the lower rectum; therefore, it is
suggested that a simulation with a tube similar in size to the FTRD should be
performed during the screening colonoscopy in order to establish whether an
endoscopic resection with FTRD is possible.
PMID- 26438204
TI - Special Issue on Pan American Biofuel and Bioenergy Sustainability.
PMID- 26438203
TI - Microglia processes associate with diffusely injured axons following mild
traumatic brain injury in the micro pig.
AB - BACKGROUND: Mild traumatic brain injury (mTBI) is an all too common occurrence
that exacts significant personal and societal costs. The pathophysiology of mTBI
is complex, with reports routinely correlating diffuse axonal injury (DAI) with
prolonged morbidity. Progressive chronic neuroinflammation has also recently been
correlated to morbidity, however, the potential association between
neuroinflammatory microglia and DAI is not well understood. The majority of
studies exploring neuroinflammatory responses to TBI have focused on more chronic
phases of injury involving phagocytosis associated with Wallerian change. Little,
however, is known regarding the neuroinflammatory response seen acutely following
diffuse mTBI and its potential relationship to early DAI. Additionally, while
inflammation is drastically different in rodents compared to humans, pigs and
humans share very similar inflammatory profiles and responses. METHODS: In the
current study, we employed a modified central fluid percussion model in micro
pigs. Using this model of diffuse mTBI, paired with various immunohistological
endpoints, we assessed the potential association between acute thalamic DAI and
neuroinflammation 6 h following injury. RESULTS: Injured micro pigs displayed
substantial axonal damage reflected in the presence of APP+ proximal axonal
swellings, which were particularly prominent in the thalamus. In companion, the
same thalamic sites displayed extensive neuroinflammation, which was observed
using Iba-1 immunohistochemistry. The physical relationship between microglia and
DAI, assessed via confocal 3D analysis, revealed a dramatic increase in the
number of Iba-1+ microglial processes that contacted APP+ proximal axonal
swellings compared to uninjured myelinated thalamic axons in sham animals.
CONCLUSIONS: In aggregate, these studies reveal acute microglial process
convergence on proximal axonal swellings undergoing DAI, an interaction not
previously recognized in the literature. These findings transform our
understanding of acute neuroinflammation following mTBI and may suggest its
potential as a diagnostic and/or a therapeutic target.
PMID- 26438205
TI - The impact of an unpredictable context and intolerance of uncertainty on the
electrocortical response to monetary gains and losses.
AB - There is growing evidence that unpredictability and uncertainty can alter reward
system functioning. The present study examined the impact of (1) a task
irrelevant unpredictable relative to predictable context and (2) individual
differences in intolerance of uncertainty (IU) on the reward-related positivity
(RewP), an event-related potential (ERP) response to monetary gains relative to
losses. Specifically, 64 participants listened to predictable and unpredictable
tone sequences while electroencephalography was recorded during a monetary
gambling task. Participants also completed the Intolerance of Uncertainty Scale,
which measures both cognitive distress (prospective IU) and behavioral inhibition
(inhibitory IU) elicited by uncertainty, in addition to the Depression Anxiety
Stress Scale-21 and Penn State Worry Questionnaire. Results indicated that the
RewP was reduced during the unpredictable relative to the predictable context.
Greater self-reported anxiety elicited by the unpredictable context was
associated with a decreased RewP, and a decreased RewP was associated with poorer
lose-shift behavioral adjustment. Furthermore, the RewP mediated the relationship
between self-reported anxiety elicited by the unpredictable context and lose
shift behavioral adjustment. The IU subscales demonstrated the opposite
relationship with the RewP across both contexts-inhibitory IU was associated with
an attenuated RewP and prospective IU was associated with an enhanced RewP. In
contrast, anxiety, depression, stress, and worry symptomatology were not
associated with the RewP. This is the first study to demonstrate that an
unpredictable context and individual differences in the degree to which people
cannot tolerate uncertainty impact an ERP measure of reward system functioning.
PMID- 26438206
TI - Assessing the utility of ICU admission for octogenarians.
AB - BACKGROUND: Advanced age is associated with increased severity of acute critical
illnesses and admission to ICU. Despite advances in the support for older
critically ill patients, the short- and long-term mortality rates remain
substantial. The purpose of this study is to analyze the factors influencing the
outcome of a geriatric population admitted to the ICU. METHODS: A single-center,
prospective, observational study was conducted among all geriatric patients, 80
years or older, admitted to ICU during a 6-month study period. RESULTS: Fifty-two
patients were admitted. Mean age was 85.1 years (range 80-96), mean APACHE-II
score was 24.7 (range 11-40), and mean frailty score was 5.8 (range 3-8). Thirty
nine (75 %) patients received mechanical ventilation, and 31 (59.7 %) were on
vasoactive therapy. Twenty-four (46.3 %) patients died during their hospital
admission, and 13 (25 %) of them expired in ICU. DISCUSSION: Advanced age, needs
for vasopressor therapy, and mechanical ventilation are independent predictive
factors of adverse outcome. Pre-admission functional status was not independently
associated with unfavorable outcome.
PMID- 26438207
TI - Serum gamma-glutamyltranspeptidase and oxidative stress in subjectively healthy
women: an association with menopausal stages.
AB - BACKGROUND: Gamma-glutamyltransferase (gamma-GT) is used as a marker of alcohol
related pathology, while gamma-GT is recently considered to be an oxidative
stress marker. AIM: The present study aimed to investigate the correlation
between the oxidative status and gamma-GT levels, in association with menopausal
stages. METHODS: In total, 252 women, who were subjectively healthy, were divided
into three groups: premenopausal, perimenopausal, and postmenopausal. The
circulating oxidative status was evaluated by the diacron-reactive oxygen
metabolite (d-ROM) test. In addition to serum gamma-GT, routine blood
investigations, including lipid, glucose, and inflammatory parameters, were
performed. RESULTS: The median gamma-GT level was 17 U/L and the mean d-ROM level
was 335 Carr U in all subjects. On multiple regression analysis, independent
significant positive correlations were observed between d-ROM and high
sensitivity CRP levels in three groups, while there was a significant positive
correlation between d-ROM and gamma-GT levels only in the premenopausal group but
not in the perimenopausal and postmenopausal groups. DISCUSSION: The significant
relationship between d-ROM and gamma-GT at active estrogen stage may indicate a
different oxidative stress condition by memopausal stage. The reasons of this
relationship should be further explored. CONCLUSION: A positive relationship
between d-ROM and gamma-GT levels, both as known as oxidative stress-related
markers, could exist in premenopausal women.
PMID- 26438208
TI - Response to Letter to the Editor, "Impact of Overloading on Temporomandibular
Joint Osteoarthritis".
PMID- 26438209
TI - Letter to the Editor: Impact of Overloading on Temporomandibular Joint
Osteoarthritis.
PMID- 26438210
TI - Preventing Childhood Caries: A Review of Recent Behavioral Research.
AB - The etiology of dental caries reflects a complex interplay of biochemical,
microbial, genetic, social and physical environmental, and health-influencing
behavioral factors. This review updates the literature on the efficacy of
behavioral approaches to caries prevention for children up to 18 y of age.
Included were studies of behavioral interventions implemented at individual,
family, and community levels that assessed results in terms of reductions in
caries increments. Only those reports published since 2011 were considered.
Outcomes were variable, although motivational interviewing, which involves
individuals in decisions about oral health within the context of their respective
life circumstances, proved effective in 3 of 4 reported studies, and more
definitive trials are underway. Recommendations for future research include
examinations of the cost-effectiveness of interventions, as well as work focused
on understanding the mechanisms underlying oral health behavior change and
variables that may mediate or moderate responses to interventions.
PMID- 26438212
TI - Molecular Basis for Differential Sensitivity of alpha-Conotoxin RegIIA at Rat and
Human Neuronal Nicotinic Acetylcholine Receptors.
AB - alpha-Conotoxins, as nicotinic acetylcholine receptor (nAChR) antagonists, are
powerful tools for dissecting biologic processes and guiding drug development.
The alpha3beta2 and alpha3beta4 nAChR subtypes are expressed in the central and
peripheral nervous systems and play a critical role in various pathophysiological
conditions ranging from nicotine addiction to the development and progression of
lung cancer. Here we used the alpha4/7-conotoxin RegIIA, a disulfide-bonded
peptide from the venom of Conus regius, and its analog [N11A,N12A]RegIIA to probe
the specific pharmacological properties of rat and human nAChR subtypes. nAChR
subtypes were heterologously expressed in Xenopus oocytes and two-electrode
voltage clamp recordings used to investigate the effects of the peptides on nAChR
activity. RegIIA potently inhibited currents evoked by acetylcholine (ACh) at rat
alpha3beta2 (IC50 = 10.7 nM), whereas a 70-fold lower potency was observed at
human alpha3beta2 nAChR (IC50 = 704.1 nM). Conversely, there were no species
specific differences in sensitivity to RegIIA at the alpha3beta4 nAChR. Receptor
mutagenesis and molecular dynamics studies revealed that this difference can be
attributed primarily to a single amino acid change: Glu198 on the rat alpha3
subunit corresponding to a proline on the human subunit. These findings reveal a
novel species- and subunit-specific receptor-antagonist interaction.
PMID- 26438211
TI - Microbial Nucleic Acid Sensing in Oral and Systemic Diseases.
AB - One challenge in studying chronic infectious and inflammatory disorders is
understanding how host pattern recognition receptors (PRRs), specifically toll
like receptors (TLRs), sense and respond to pathogen- or damage-associated
molecular patterns, their communication with each other and different components
of the immune system, and their role in propagating inflammatory stages of
disease. The discovery of innate immune activation through nucleic acid
recognition by intracellular PRRs such as endosomal TLRs (TLR3, TLR7, TLR8, and
TLR9) and cytoplasmic proteins (absent in melanoma 2 and DNA-dependent activator
of interferon regulatory factor) opened a new paradigm: Nucleic acid sensing is
now implicated in multiple immune and inflammatory conditions (e.g.,
atherosclerosis, cancer), viral (e.g., human papillomavirus, herpes virus) and
bacterial (e.g., Helicobacter pylori, pneumonia) diseases, and autoimmune
disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis). Clinical
investigations reveal the overexpression of specific nucleic acid sensors in
diseased tissues. In vivo animal models show enhanced disease progression
associated with receptor activation. The involvement of nucleic acid sensors in
various systemic conditions is further supported by studies reporting receptor
knockout mice being either protected from or prone to disease. TLR9-mediated
inflammation is also implicated in periodontal diseases. Considering that
persistent inflammation in the oral cavity is associated with systemic diseases
and that oral microbial DNA is isolated at distal sites, nucleic acid sensing may
potentially be a link between oral and systemic diseases. In this review, we
discuss recent advances in how intracellular PRRs respond to microbial nucleic
acids and emerging views on the role of nucleic acid sensors in various systemic
diseases. We also highlight new information on the role of intracellular PRRs in
the pathogenesis of oral diseases including periodontitis and oral cavity cancer,
which might offer future possibilities for disease prevention and therapy.
PMID- 26438213
TI - Long-Range Inhibitor-Induced Conformational Regulation of Human IRE1alpha
Endoribonuclease Activity.
AB - Activation of the inositol-requiring enzyme-1 alpha (IRE1alpha) protein caused by
endoplasmic reticulum stress results in the homodimerization of the N-terminal
endoplasmic reticulum luminal domains, autophosphorylation of the cytoplasmic
kinase domains, and conformational changes to the cytoplasmic endoribonuclease
(RNase) domains, which render them functional and can lead to the splicing of X
box binding protein 1 (XBP 1) mRNA. Herein, we report the first crystal
structures of the cytoplasmic portion of a human phosphorylated IRE1alpha dimer
in complex with (R)-2-(3,4-dichlorobenzyl)-N-(4-methylbenzyl)-2,7
diazaspiro(4.5)decane-7-carboxamide, a novel, IRE1alpha-selective kinase
inhibitor, and staurosporine, a broad spectrum kinase inhibitor. (R)-2-(3,4
dichlorobenzyl)-N-(4-methylbenzyl)-2,7-diazaspiro(4.5)decane-7-carboxamide
inhibits both the kinase and RNase activities of IRE1alpha. The inhibitor
interacts with the catalytic residues Lys599 and Glu612 and displaces the kinase
activation loop to the DFG-out conformation. Inactivation of IRE1alpha RNase
activity appears to be caused by a conformational change, whereby the alphaC
helix is displaced, resulting in the rearrangement of the kinase domain-dimer
interface and a rotation of the RNase domains away from each other. In contrast,
staurosporine binds at the ATP-binding site of IRE1alpha, resulting in a dimer
consistent with RNase active yeast Ire1 dimers. Activation of IRE1alpha RNase
activity appears to be promoted by a network of hydrogen bond interactions
between highly conserved residues across the RNase dimer interface that place key
catalytic residues poised for reaction. These data implicate that the
intermolecular interactions between conserved residues in the RNase domain are
required for activity, and that the disruption of these interactions can be
achieved pharmacologically by small molecule kinase domain inhibitors.
PMID- 26438214
TI - Elevated Serum Levels of SCUBE1, a Marker for Coagulation, in Patients with
Breast Cancer.
AB - Breast cancer (BC) is the most common cancer among women and a major cause of
death. Signal Peptide-Cub-Epidermal growth factor domain-containing protein-1
(SCUBE1) is secreted under hypoxia and inflammatory conditions from platelet
alpha granules. Its biological function is uncertain, although it may be a
procoagulant substance in cancer patients. SCUBE1 is useful for identifying
thrombotic diseases, including cancers and acute coronary syndromes. D-dimer
reflects the relationship between coagulation activation and fibrinolysis;
namely, thrombosis and D-dimer levels are closely linked. This is the first
investigation of the potential diagnostic and prognostic value of SCUBE1 levels
in patients with BC. Fifty patients and 33 age-matched and body mass index
matched healthy controls were enrolled. Blood samples were collected before
chemotherapy regimens commenced. Serum SCUBE1 and D-dimer levels were measured
before adjuvant chemotherapy and were compared to the healthy controls. SCUBE1
levels were determined using an enzyme-linked immunosorbent assay (ELISA) method.
SCUBE1 and D-dimer levels were significantly higher in patients than in the
controls (p = 0.03 and p < 0.001, respectively). A cut-off value of 1.55 ng/mL
for SCUBE1 was associated with 62% sensitivity and 72.7% specificity and with
positive predictive value of 77.5% and negative predictive value of 55.8%. Two
patients with high SCUBE1 and D-dimer levels also developed pulmonary embolism.
SCUBE1 may indicate hypercoagulability in patients with BC and thus help identify
patients at greater risk of thrombosis and requiring anti-thrombosis treatment.
SCUBE1 may also be used as an assistant test for identifying patients at risk of
BC.
PMID- 26438215
TI - Intragel photoreduction of aryl halides by green-to-blue upconversion under
aerobic conditions.
AB - The first proof of concept for the application of intragel green-to-blue photon
upconversion to a chemical reaction is reported. The developed method allows the
photoreduction of aryl halides at room temperature under aerobic conditions.
PMID- 26438216
TI - Label-free blood serum detection by using surface-enhanced Raman spectroscopy and
support vector machine for the preoperative diagnosis of parotid gland tumors.
AB - BACKGROUND: It is difficult for the parotid gland neoplasms to make an accurate
preoperative diagnosis due to the restriction of biopsy in the parotid gland
neoplasms. The aim of this study is to apply the surface-enhanced Raman
spectroscopy (SERS) method for the blood serum biochemical detection and use the
support vector machine for the analysis in order to develop a simple but accurate
blood serum detection for preoperative diagnosis of the parotid gland neoplasms.
METHODS: The blood serums were collected from four groups: the patients with
pleomorphic adenoma, the patients with Warthin's tumor, the patients with
mucoepidermoid carcinoma and the volunteers without parotid gland neoplasms. Au
nanoparticles (Au NPs) were mixed with the blood serum as the SERS active
nanosensor to enhance the Raman scattering signals produced by the various
biochemical materials and high quality SERS spectrum were obtained by using the
Raman microscope system. Then the support vector machine was utilized to analyze
the differences of the SERS spectrum from the blood serum of different groups and
established a diagnostic model to discriminate the different groups. RESULTS: It
was demonstrated that there were different intensities of SERS peaks assigned to
various biochemical changes in the blood serum between the parotid gland tumor
groups and normal control group. Compared with the SERS spectra of the normal
serums, the intensities of peaks assigned to nucleic acids and proteins increased
in the SERS spectra of the parotid gland tumor serums, which manifested the
differences of the biochemical metabolites in the serum from the patients with
parotid gland tumors. When the leave-one-sample-out method was used, support
vector machine (SVM) played an outstanding performance in the classification of
the SERS spectra with the high accuracy (84.1 % ~ 88.3 %), sensitivity (82.2 % ~
97.4 %) and specificity (73.7 % ~ 86.7 %). Though the accuracy, sensitivity and
specificity decreased in the leave-one-patient-out cross validation, the
mucoepidermoid carcinoma was still easier to diagnose than other tumors.
DISCUSSION: The specific molecular differences of parotid gland tumors and normal
serums were significantly demonstrated through the comparison between the various
SERS spectra.But compared with the serum SERS spectra reported in the other
studies, some differences exist between the spectra in this study and the ones
reported in the lietratures. These differences may result from the various nano
particles, the different preparation of serum and equipment parameters, and we
could need a further research to find an exact explanation.Based on the SERS
spectra of the serum samples, SVM have shown a giant potential to diagnose the
parotid gland tumors in our preliminary study. However, different cross
validaiton methods could effect the accuracy and a further study involing a great
number of samples should be needed. CONCLUSIONS: This exploratory research
demonstrated the great potential of SERS combined with SVM into a non-invasive
clinical diagnostic method for preoperative diagnosis of parotid gland tumors.
And the internal relation between the spectra and patients should be established
in the further study.
PMID- 26438217
TI - Treatment Concerns and Functional Impairment in Pediatric Anxiety.
AB - Although there are efficacious, evidence-based treatments for anxiety disorders,
youth often experience delays in seeking therapy. Myriad reasons may contribute
to this lag in treatment initiation, with some youth possessing concerns about
therapy. Treatment concerns are broadly characterized by worries/ambivalence
about seeking treatment, including concerns about the negative reactions,
consequences, and inconvenience of treatment. As no studies exist for youth with
anxiety disorders, this study examined the phenomenology of treatment concerns in
119 treatment-seeking, anxious youth and utilized a structural equation model to
examine the relationship between child anxiety, depressive symptoms, treatment
concerns, and anxiety-related functional impairment. Over 90 % of the children
positively endorsed some type of treatment-related fear, with the most frequently
expressed concern being that therapy would take too much time (50.4 %). Based on
the model, both child anxiety and depressive symptoms predicted functional
impairment, and treatment concerns mediated the relationship between child
anxiety and functional impairment.
PMID- 26438218
TI - Relationship between endodormancy, FLOWERING LOCUS T and cell cycle genes in
Vitis vinifera.
AB - MAIN CONCLUSION: In grapevines, the increased expression of VvFT , genes involved
in the photoperiodic control of seasonal growth ( VvAP1, VvAIL2 ) and cell cycle
genes ( VvCDKA, VvCDKB2, VvCYCA1, VvCYCB, VvCYCD3.2 ) in the shoot apex relative
to the latent bud, suggests a high mitotic activity of the apex which could
prevent them to enter into endodormancy. Additionally, the up-regulation of these
genes by the dormancy-breaking compound hydrogen cyanamide (H 2 CN 2 ) strongly
suggests that VvFT plays a key role in regulating transcriptionally cell cycle
genes. At the end of the growing season, short-day (SD) photoperiod induces the
transition of latent grapevine buds (Vitis vinifera L) from paradormancy (PD) to
endodormancy (ED), which allows them to survive the cold temperatures of winter.
Meanwhile, the shoot apex gradually decreases its growth without entering into
ED, and as a result of the fall of temperatures at the beginning of autumn, dies.
To understand developmental differences and contrasting responses to
environmental cues between both organs, the expression of cell cycle genes, and
of genes involved in photoperiodic control of seasonal growth in trees, such as
FLOWERING LOCUS T (FT), APETALA1 (AP1) and AINTEGUMENTA-like (AIL) was analyzed
at the shoot apex and latent buds of vines during the transition from PD to ED.
After shift to SD photoperiod, increased expression of cell cycle genes in the
shoot apex suggests a high mitotic activity in this organ which could prevent
them from entering into ED. Additionally, the increased expression of VvFT,
VvAP1and VvAIL2 in the shoot apex, and the up-regulation of VvFT, VvAP1and cell
cycle genes VvCDKA, VvCDKB2, VvCYCA.1, by the dormancy-breaking compound hydrogen
cyanamide (H2CN2), strongly suggests that VvFT plays a key role in regulating
transcriptionally cell cycle genes, giving thus, more support to the model for
photoperiodic control of seasonal growth in trees. Furthermore, downregulation of
VvFT by the SD photoperiod detected in leaves and buds of grapevines highlights
the importance of VvFT in the induction of growth cessation and in ED
development, probably by regulating the expression of cell cycle genes.
PMID- 26438219
TI - Limited transpiration under high vapor pressure deficits of creeping bentgrass by
application of Daconil-Action.
AB - MAIN CONCLUSION: First observation that chemical spray can induce limited
transpiration rate under high vapor pressure deficit. It appears that acibenzolar
may be key in inducing this water conservation trait. Irrigation and water use
have become major issues in management of turfgrasses. Plant health products that
have been introduced into the turfgrass market have been observed to improve
plant performance in water stress conditions. In this study, we evaluated whether
a selection of common plant health products alter the ability of creeping
bentgrass (Agrostis stolonifera L.) to control transpiration under high vapor
pressure deficit (VPD). The plant health treatments--Daconil Action, Insignia,
and Signature--were applied to plots on golf course putting greens located in
Raleigh NC and in Scottsdale, AZ. Using intact cores removed from the putting
greens, transpiration rates were measured over a range of VPDs in controlled
conditions. In all cases stretching over a 3-year period, bentgrass cores from
field plots treated with Daconil-Action limited transpiration under high VPD
conditions, while check treatments with water, and others treated with Insignia
or Signature did not. Transpiration control became engaged when VPDs reached
values ranging from 1.39 to 2.50 kPa, and was not strongly influenced by the
field temperature at which the bentgrass was growing. Because all plots in NC had
been treated with chlorothalonil-the key ingredient in Daconil Action to control
diseases-it was concluded that the likely chemical ingredient in Daconil Action
triggering the transpiration control response was acibenzolar. This is the first
evidence that the limited-transpiration trait can be induced by a chemical
application, and it implies significant potential for ameliorating drought
vulnerability in cool-season turfgrasses, and likely other plant species.
PMID- 26438220
TI - The Impact of Medical and Surgical Treatment for Benign Prostatic Hypertrophy on
Erectile Function.
AB - There is a well-known link between treatment for lower urinary tract symptoms
(LUTS) and erectile dysfunction. Surgical and medical management of LUTS all have
side effect profiles which may affect erectile dysfunction, ejaculatory
dysfunction, or libido. These should be taken into consideration during patient
counseling. This article reviews the common side effects of the medical and
surgical treatments of LUTS.
PMID- 26438221
TI - Clocks do not tick in unison: isolation of Clock and vrille shed new light on the
clockwork model of the sand fly Lutzomyia longipalpis.
AB - BACKGROUND: Behavior rhythms of insect vectors directly interfere with the
dynamics of pathogen transmission to humans. The sand fly Lutzomyia longipalpis
is the main vector of visceral leishmaniasis in America and concentrates its
activity around dusk. Despite the accumulation of behavioral data, very little is
known about the molecular bases of the clock mechanism in this species. This
study aims to characterize, within an evolutionary perspective, two important
circadian clock genes, Clock and vrille. FINDINGS: We have cloned and isolated
the coding sequence of L. longipalpis' genes Clock and vrille. The former is
structured in eight exons and encodes a protein of 696 amino acids, and the
latter comprises three exons and translates to a protein of 469 amino acids. When
compared to other insects' orthologues, L. longipalpis CLOCK shows a high degree
of conservation in the functional domains bHLH and PAS, but a much shorter
glutamine-rich (poly-Q) C-terminal region. As for L. longipalpis VRILLE, a high
degree of conservation was found in the bZIP domain. To support these
observations and provide an elegant view of the evolution of both genes in
insects, phylogenetic analyses based on maximum-likelihood and Bayesian
inferences were performed, corroborating the previously known insect systematics.
CONCLUSIONS: The isolation and phylogenetic analyses of Clock and vrille
orthologues in L. longipalpis bring novel and important data to characterize this
species' circadian clock. Interestingly, the poly-Q shortening observed in CLOCK
suggests that its transcription activity might be impaired and we speculate if
this effect could be compensated by other clock factors such as CYCLE.
PMID- 26438222
TI - Did studies on HFOV fail to improve ARDS survival because they did not decrease
VILI? On the potential validity of a physiological concept enounced several
decades ago.
AB - High frequency oscillatory ventilation (HFOV) has been the subject of extensive
physiological research for 30 years and even more so of an intense debate on its
potential usefulness in the treatment of acute respiratory distress syndrome
(ARDS). This technique has been enthusiastically promoted by some teams until two
high-quality randomized clinical trials in adults with ARDS showed that HFOV did
not decrease and might have even increased mortality. As a consequence of these
results, physiological concepts such as atelectrauma and biotrauma on which ARDS
management with HFOV were based should be reexamined. In contrast, the concept of
volutrauma, i.e., end-inspiratory overdistension, as the cause for ventilator
induced lung injury might help explain excess mortality during mechanical
ventilation of ARDS when inspiratory volumes are too high. This is what might
have happened during one of the recent studies on HFOV. Failure of this complex
technique must be put in perspective with the dramatic improvement of ARDS
prognosis with very simple interventions such as tidal volume reduction, early
pharmacological paralysis, and prone positioning which all limited end
inspiratory volume.
PMID- 26438223
TI - Effects of packed red blood cell storage duration on post-transfusion clinical
outcomes: a meta-analysis and systematic review.
AB - PURPOSE: There is substantial conjecture regarding the clinical significance of
packed red blood cell (PRBC) changes that occur during in vitro storage. Here, we
present a meta- and systematic analysis of adult studies published between 1994
and 2015 with the aim of updating existing quantitative reviews and providing a
comprehensive cover of the six most commonly studied outcomes-mortality,
infection, renal dysfunction, multiple organ dysfunction syndrome (MODS),
thrombotic complications and prolonged hospital length of stay. METHODS:
Computerised searches of Pubmed and EMBASE identified publications that reported
target outcomes and PRBC storage duration prior to transfusion. Bibliographies of
relevant literature were manually searched to incorporate missed studies.
Randomised controlled trial (RCT) data was meta-analysed using a random effects
model with Cochrane Collaboration Review Manager (RevMan) version 5.1 software.
Observational investigations were systematically reviewed. RESULTS: Sixty-four
papers were selected covering 462,581 patients with the majority of studies being
observational in nature. Meta-analysis of eight RCTs demonstrated a trend towards
decreased mortality with stored PRBC transfusion; albeit this effect was not
statistically significant (OR 0.91, 95 % CI 0.78-1.05, p = 0.20). In a small
subset of intensive care unit (ICU), cardiac surgery and trauma patients;
observational studies suggested that prolonged storage may be correlated with
increased mortality. Trauma and cardiac surgery patients appeared to be most
susceptible to the potential infectious complications of stored PRBCs. Stored
PRBCs were unlikely to affect thrombotic complications or hospital length of
stay. There were inadequate data to determine whether stored PRBCs had clinically
relevant effects on renal dysfunction and MODS. CONCLUSION: Although literature
presents a concerning picture of potential storage complications, current
findings are too inconsistent to drive changes in clinical practice. Results from
current RCTs will likely play a role in PRBC age guidelines for cardiac surgery
and ICU patients. However, these studies may be less efficacious at detecting
small effects that are limited to specific subpopulations.
PMID- 26438225
TI - TaylorActive--Examining the effectiveness of web-based personally-tailored videos
to increase physical activity: a randomised controlled trial protocol.
AB - BACKGROUND: Physical inactivity levels are unacceptably high and effective
interventions that can increase physical activity in large populations at low
cost are urgently needed. Web-based interventions that use computer-tailoring
have shown to be effective, though people tend to 'skim' and 'scan' text on the
Internet rather than thoroughly read it. The use of online videos is, however,
popular and engaging. Therefore, the aim of this 3-group randomised controlled
trial is to examine whether a web-based physical activity intervention that
provides personally-tailored videos is more effective when compared with
traditional personally-tailored text-based intervention and a control group.
METHODS/DESIGN: In total 510 Australians will be recruited through social media
advertisements, e-mail and third party databases. Participants will be randomised
to one of three groups: text-tailored, video-tailored, or control. All groups
will gain access to the same web-based platform and a library containing brief
physical activity articles. The text-tailored group will additionally have access
to 8 sessions of personalised physical activity advice that is instantaneously
generated based on responses to brief online surveys. The theory-based advice
will be provided over a period of 3 months and address constructs such as self
efficacy, motivation, goal setting, intentions, social support, attitudes,
barriers, outcome expectancies, relapse prevention and feedback on performance.
Text-tailored participants will also be able to complete 7 action plans to help
them plan what, when, where, who with, and how they will become more active.
Participants in the video-tailored group will gain access to the same
intervention content as those in the text-tailored group, however all sessions
will be provided as personalised videos rather than text on a webpage. The
control group will only gain access to the library with generic physical activity
articles. The primary outcome is objectively measured physical activity.
Secondary outcomes include website engagement and retention, quality of life,
depression, anxiety, stress, sitting time, sleep and psychosocial correlates of
physical activity. Outcomes will be measured at baseline, 3, and 9 months.
DISCUSSION: This study presents an ideal opportunity to study the effectiveness
of an isolated feature within a web-based physical activity intervention and the
knowledge generated from this study will help to increase intervention
effectiveness. TRIAL REGISTRATION: Australian New-Zealand Clinical Trial
Registry: ACTRN12615000057583 . Registered 22 January 2015. CQUniversity Ethics
Project Number: H14/07-163.
PMID- 26438226
TI - The impacts of withdrawal and replacement of general practitioner services on
aeromedical service trends: a 13-year interrupted time-series study in Tennant
Creek, Northern Territory.
AB - BACKGROUND: The Royal Flying Doctor Service (RFDS) provides aeromedical care to
patients during fixed-wing transport over vast distances to healthcare
unavailable in rural or remote communities. This study examined the relationship
between changes in local accessibility to primary healthcare services and rates
of aeromedical service use over time. METHODS: This was a 13-year interrupted
time-series study (1999-2012) in Tennant Creek, Northern Territory. Quarterly
aeromedical service use for primary care sensitive conditions were calculated and
exposure to general practice (GP) services was characterised over time with
events modelled as intervention variables: (a) GP service withdrawal (Nov-2004);
and (b) GP service replacement (Dec-2006). Intervention effects were estimated
using PROC ARIMA in SAS after examination of the time-series structure. RESULTS:
GP withdrawal resulted in an immediate and sustained doubling in quarterly
aeromedical service use (+11.8 services per quarter) and GP service replacement
had no significant effect. DISCUSSION: Large and immediate increases in
aeromedical service use result from the loss of local GPservices yet, in this
case, replacement with a new GP service, 2-years hence, did not ameliorate that
effect after six years. CONCLUSIONS: These findings demonstrate the immediate
impact of GP-service loss on the rates ofaeromedical transfer of patients from
this remote community and lend caution to expectations about thetimeline over
which newly implemented primary health care services in such contexts can
mitigate the impact of such a loss.
PMID- 26438227
TI - Deep brain stimulation of the subthalamic nucleus: histological verification and
9.4-T MRI correlation.
AB - BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) using
an MRI-guided and MRI-verified technique without microelectrode recording is an
effective and safe surgical treatment for patients with Parkinson's disease (PD).
OBJECTIVES: To assess the anatomical accuracy of lead placement after MRI-guided,
MRI-verified STN DBS using post-mortem histology and high-field MRI at 9.4 T.
METHODS: We conducted post-mortem analysis of a patient's brain who had had MRI
guided, MRI-verified STN DBS for PD, using 9.4-T MRI and histology. After death,
the brain was retrieved and a block including the electrode tracks down to the
mesencephalon was examined with high-field MRI at 9.4 T and histological
analysis. RESULTS: High-field MRI images and corresponding histological
examination showed that each electrode track ended within the intended target
area, and that DBS did not cause significant neuroparenchymal tissue damage.
CONCLUSIONS: This study supports the anatomical accuracy of the MRI-guided and
MRI-verified method of STN DBS.
PMID- 26438224
TI - Task force on management and prevention of Acinetobacter baumannii infections in
the ICU.
AB - INTRODUCTION: Acinetobacter baumannii constitutes a dreadful problem in many ICUs
worldwide. The very limited therapeutic options available for these organisms are
a matter of great concern. No specific guidelines exist addressing the prevention
and management of A. baumannii infections in the critical care setting. METHODS:
Clinical microbiologists, infectious disease specialists and intensive care
physicians were invited by the Chair of the Infection Section of the ESICM to
participate in a multidisciplinary expert panel. After the selection of
clinically relevant questions, this document provides recommendations about the
use of microbiological techniques for identification of A. baumannii in clinical
laboratories, antibiotic therapy for severe infections and recommendations to
control this pathogen in outbreaks and endemic situations. Evidence supporting
each statement was graded according to the European Society of Clinical
Microbiology and Infection Diseases (ESCMID) grading system. RESULTS: Empirical
coverage of A. baumannii is recommended in severe infections (severe sepsis or
septic shock) occurring during an A. baumannii outbreak, in an endemic setting,
or in a previously colonized patient. For these cases, a polymyxin is suggested
as part of the empirical treatment in cases of a high suspicion of a carbapenem
resistant (CR) A. baumannii strain. An institutional program including staff
education, promotion of hand hygiene, strict contact and isolation precautions,
environmental cleaning, targeted active surveillance, and antimicrobial
stewardship should be instituted and maintained to combat outbreaks and endemic
situations. CONCLUSIONS: Specific recommendations about prevention and management
of A. baumannii infections in the ICU were elaborated by this multidisciplinary
panel. The paucity of randomized controlled trials is noteworthy, so these
recommendations are mainly based on observational studies and pharmacodynamics
modeling.
PMID- 26438228
TI - Transdiscal C6-C7 contralateral C7 nerve root transfer in the surgical repair of
brachial plexus avulsion injuries.
AB - BACKGROUND: Repair of complete brachial plexus avulsion injuries may require
contralateral C7 nerve root transfer. The available techniques might allow direct
neuroraphy in about 50 % of cases but the others require interposing nerve grafts
or humeral shaft shortening. We aimed to see if transdiscal C6-C7 contralateral
C7 nerve root transfer is technically feasible and if it allows direct coaptation
with the contralateral nerve roots in 100 % of cases. METHODS: In ten fresh
frozen adult cadavers, the C7 nerve root was sectioned just before it connects
with other brachial plexus branches and re-routed though the C6-C7 disc space to
the contralateral side. A complete C6-C7 discectomy was performed and the disc
space kept open with the aid of an autologous iliac crest bone graft. RESULTS:
Transdiscal C6-C7 contralateral C7 nerve root transfer is technically feasible.
In our cadavers, it provided 5.3 +/- 1.2 SDcm of extra length that allowed direct
coaptation with the contralateral nerve roots, mainly C8 and T1. CONCLUSIONS:
Transdiscal C6-C7 contralateral C7 nerve root transfer is technically feasible.
In our dissections it lengthens the available C7 nerve root stump by 5.3 +/-
1.2SDcm. The increase was 4 cm versus the retropharyngeal route making direct
coaptation with the contralateral C8 and T1 nerve roots possible.
PMID- 26438229
TI - Metastasis of an occult pulmonary carcinoma into meningioma: a case report.
AB - Tumour-to-tumour metastasis is an infrequent pathological phenomenon. Meningioma
is the most common intracranial tumour where metastatic deposits may be found,
the majority of which arise from breast and lung cancers. We describe an unusual
case of occult pulmonary carcinoma metastasis into the intracranial meningioma. A
77-year old lady presented with acutely deteriorating hemiparesis. Her previous
medical history was unremarkable. Radiological imaging revealed an expansive
lesion, classified as meningioma, which was located parasagittally in the right
premotor area. A well-capsulated tumour attached to the dura was removed
surgically. The pathological examination demonstrated a mixture of angiomatous
meningioma and pulmonary adenocarcinoma. Possible explanations for the
development of a composite tumour and pathophysiology are described.
PMID- 26438230
TI - Radical hysterectomy with or without para-aortic lymphadenectomy for patients
with stage IB2, IIA2, and IIB cervical cancer: outcomes for a series of 308
patients.
AB - BACKGROUND: Although many studies have already shown that lymph node metastasis
is one of the major prognostic factors for cervical cancer, the therapeutic
significance of para-aortic lymphadenectomy for the surgical treatment of
cervical cancer remains controversial. METHODS: A total of 308 patients diagnosed
with stage IB2, IIA2, or IIB cervical cancer and treated with radical
hysterectomy were retrospectively investigated to assess the incidence of para
aortic lymph node metastasis and the clinicopathological factors linked to
cervical cancer prognosis. RESULTS: Para-aortic lymph node metastases were
pathologically confirmed in 13 of the 136 patients (9.6 %) who underwent para
aortic lymphadenectomy. The incidence of para-aortic lymph node metastasis was
significantly higher in the patients who had common iliac lymph node metastases
(odds ratio 31.5, p < 0.001) according to logistic regression analysis. Common
iliac lymph node metastasis was related to risk of recurrence (hazard ratio 2.43,
p = 0.003) and death (hazard ratio 2.62, p = 0.007) in Cox regression analysis.
Kaplan-Meier analysis and Cox regression analysis showed that para-aortic
lymphadenectomy did not have a positive impact on survival in 308 patients or 140
pN1 patients, but para-aortic lymphadenectomy was related to better overall
survival with a marginal trend toward significance (p = 0.053) in 30 patients
with common iliac lymph node metastasis. CONCLUSIONS: Indication for para-aortic
lymphadenectomy in the surgical treatment of stage IB2, IIA2, or IIB cervical
cancer needs to be individualized. Patients with common iliac lymph node
metastasis are possible candidates, and a prospective study is needed to clarify
this issue.
PMID- 26438232
TI - Prophage recombinases-mediated genome engineering in Lactobacillus plantarum.
AB - BACKGROUND: Lactobacillus plantarum is a food-grade microorganism with industrial
and medical relevance belonging to the group of lactic acid bacteria (LAB).
Traditional strategies for obtaining gene deletion variants in this organism are
mainly vector-based double-crossover methods, which are inefficient and
laborious. A feasible possibility to solve this problem is the recombineering,
which greatly expands the possibilities for engineering DNA molecules in vivo in
various organisms. RESULTS: In this work, a double-stranded DNA (dsDNA)
recombineering system was established in L. plantarum. An exonuclease encoded by
lp_0642 and a potential host-nuclease inhibitor encoded by lp_0640 involved in
dsDNA recombination were identified from a prophage P1 locus in L. plantarum
WCFS1. These two proteins, combined with the previously characterized single
strand annealing protein encoded by lp_0641, can perform homologous recombination
between a heterologous dsDNA substrate and host genomic DNA. Based on this, we
developed a method for marker-free genetic manipulation of the chromosome in L.
plantarum. CONCLUSIONS: This Lp_0640-41-42-mediated recombination allowed easy
screening of mutants and could serve as an alternative to other genetic
manipulation methods. We expect that this method can help for understanding the
probiotic functionality and physiology of LAB.
PMID- 26438231
TI - Protein repair L-isoaspartyl methyltransferase 1 (PIMT1) in rice improves seed
longevity by preserving embryo vigor and viability.
AB - Damaged proteins containing abnormal isoaspartyl (isoAsp) accumulate as seeds age
and the abnormality is thought to undermine seed vigor. Protein-L-isoaspartyl
methyltransferase (PIMT) is involved in isoAsp-containing protein repair. Two
PIMT genes from rice (Oryza sativa L.), designated as OsPIMT1 and OsPIMT2, were
isolated and investigated for their roles. The results indicated that OsPIMT2 was
mainly present in green tissues, but OsPIMT1 largely accumulated in embryos.
Confocal visualization of the transient expression of OsPIMTs showed that OsPIMT2
was localized in the chloroplast and nucleus, whereas OsPIMT1 was predominately
found in the cytosol. Artificial aging results highlighted the sensitivity of the
seeds of OsPIMT1 mutant line when subjected to accelerated aging. Overexpression
of OsPIMT1 in transgenic seeds reduced the accumulation of isoAsp-containing
protein in embryos, and increased embryo viability. The germination percentage of
transgenic seeds overexpressing OsPIMT1 increased 9-15% compared to the WT seeds
after 21-day of artificial aging, whereas seeds from the OsPIMT1 RNAi lines
overaccumulated isoAsp in embryos and experienced rapid loss of seed
germinability. Taken together, these data strongly indicated that OsPIMT1-related
seed longevity improvement is probably due to the repair of detrimental isoAsp
containing proteins that over accumulate in embryos when subjected to accelerated
aging.
PMID- 26438233
TI - Unskilled but subjectively aware: Metacognitive monitoring ability and respective
awareness in low-performing students.
AB - Two studies were conducted to further examine the unskilled-and-unaware effect
and to test whether low-performing students are indeed unaware of their
(expected) lower metacognitive monitoring abilities. Postdicted judgments of
performance and second-order judgments (SOJs) were solicited to test students'
metacognitive awareness. Given that global and local judgments tend to differ
(the confidence-frequency effect), we investigated whether students'
(un)awareness pertains to both types of judgments. A first study focusing on
global judgments was conducted in a regular exam setting with 196 undergraduate
education students. A second study with 115 undergraduate education students
examined both global and local judgments. Local judgments were analyzed on an
average level and according to different signal detection theory categories
(hits, correct rejections, misses, and false alarms). In both studies, students
were grouped in four performance quartiles. The results showed that low
performing students highly overestimated their performance (they were
functionally overconfident). However, their SOJs indicated that they were less
confident in their judgments than the other students, and thus seemed to be aware
of their low ability to estimate their own performance (they were not
subjectively overconfident). This was observed for global as well as for averaged
local SOJs. Moreover, an analysis of the local judgments revealed that students'
SOJs varied depending not only on whether their judgments were accurate but also
on whether or not they thought they knew the answer to an item. In sum, SOJs
provide valuable information about students' metacognitive awareness.
PMID- 26438234
TI - Activation and selection of arithmetic facts: The role of numerical format.
AB - We examined the role of numerical format in the activation and selection of
arithmetic facts. We also explored the inhibitory nature of this mechanism. To
this end, in two experiments we manipulated the format of the operations (digit
format and word format) while participants decided whether simple additions were
correct or not. In Experiment 1, when an addition was incorrect but the result
was that of multiplying the operands (e.g., 2 + 4 = 8), participants took more
time to respond relative to a control condition where the addition's result was
incorrect but unrelated. Afterward, participants took more time to respond when
the result of multiplying the operands was presented again in a correct addition
problem (e.g., 2 + 6 = 8), suggesting that the related multiplication result in
the previous trial (e.g., 8) was inhibited to select the correct response (e.g.,
6); thus, when it was presented again in the next problem, additional time was
necessary to reactivate it. These effects were found in the digit format but not
in the word format. In Experiment 2, we considered the degree to which
participants used memory retrieval to perform the task. In participants with high
retrieval usage, the interference effects in the first and second trials were
larger for the digit format than for the word format. However, the participants
with low retrieval usage showed interference effects only for problems with
digits. These findings are discussed in terms of automaticity in retrieving
arithmetic facts to perform simple arithmetic.
PMID- 26438236
TI - The Problem with Education in Global Mental Health.
PMID- 26438235
TI - Sample selection, recruitment and participation rates in health examination
surveys in Europe--experience from seven national surveys.
AB - BACKGROUND: Health examination surveys (HESs), carried out in Europe since the
1950's, provide valuable information about the general population's health for
health monitoring, policy making, and research. Survey participation rates,
important for representativeness, have been falling. International comparisons
are hampered by differing exclusion criteria and definitions for non-response.
METHOD: Information was collected about seven national HESs in Europe conducted
in 2007-2012. These surveys can be classified into household and individual-based
surveys, depending on the sampling frames used. Participation rates of randomly
selected adult samples were calculated for four survey modules using standardised
definitions and compared by sex, age-group, geographical areas within countries,
and over time, where possible. RESULTS: All surveys covered residents not just
citizens; three countries excluded those in institutions. In two surveys,
physical examinations and blood sample collection were conducted at the
participants' home; the others occurred at examination clinics. Recruitment
processes varied considerably between surveys. Monetary incentives were used in
four surveys. Initial participation rates aged 35-64 were 45% in the Netherlands
(phase II), 54% in Germany (new and previous participants combined), 55% in
Italy, and 65% in Finland. In Ireland, England and Scotland, household
participation rates were 66%, 66% and 63% respectively. Participation rates were
generally higher in women and increased with age. Almost all participants
attending an examination centre agreed to all modules but surveys conducted in
the participants' home had falling responses to each stage. Participation rates
in most primate cities were substantially lower than the national average. Age
standardized response rates to blood pressure measurement among those aged 35-64
in Finland, Germany and England fell by 0.7-1.5 percentage points p.a. between
1998-2002 and 2010-2012. Longer trends in some countries show a more marked fall.
CONCLUSIONS: The coverage of the general population in these seven national HESs
was good, based on the sampling frames used and the sample sizes. Pre
notification and reminders were used effectively in those with highest
participation rates. Participation rates varied by age, sex, geographical area,
and survey design. They have fallen in most countries; the Netherlands data shows
that they can be maintained at higher levels but at much higher cost.
PMID- 26438237
TI - The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in
HER2-negative breast cancer patients: a randomized pilot study.
AB - BACKGROUND: Preclinical evidence shows that short-term fasting (STF) protects
healthy cells against side effects of chemotherapy and makes cancer cells more
vulnerable to it. This pilot study examines the feasibility of STF and its
effects on tolerance of chemotherapy in a homogeneous patient group with early
breast cancer (BC). METHODS: Eligible patients had HER2-negative, stage II/III
BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide)
were randomized to fast 24 h before and after commencing chemotherapy, or to eat
according to the guidelines for healthy nutrition. Toxicity in the two groups was
compared. Chemotherapy-induced DNA damage in peripheral blood mononuclear cells
(PBMCs) was quantified by the level of gamma-H2AX analyzed by flow cytometry.
RESULTS: Thirteen patients were included of whom seven were randomized to the STF
arm. STF was well tolerated. Mean erythrocyte- and thrombocyte counts 7 days post
chemotherapy were significantly higher (P = 0.007, 95 % CI 0.106-0.638 and P =
0.00007, 95 % CI 38.7-104, respectively) in the STF group compared to the non-STF
group. Non-hematological toxicity did not differ between the groups. Levels of
gamma-H2AX were significantly increased 30 min post-chemotherapy in CD45 + CD3-
cells in non-STF, but not in STF patients. CONCLUSIONS: STF during chemotherapy
was well tolerated and reduced hematological toxicity of TAC in HER2-negative BC
patients. Moreover, STF may reduce a transient increase in, and/or induce a
faster recovery of DNA damage in PBMCs after chemotherapy. Larger studies,
investigating a longer fasting period, are required to generate more insight into
the possible benefits of STF during chemotherapy. TRIAL REGISTRATION:
ClinicalTrials.gov: NCT01304251 , March 2011.
PMID- 26438238
TI - Cost of illness of breast cancer in Japan: trends and future projections.
AB - BACKGROUND: Breast cancer is a major cause of death for women in Japan. The
objectives of this study were to estimate and project the economic burden
associated with breast cancer in Japan and identify the key factors that drive
the change of the economic burden of breast cancer. METHODS: We calculated the
cost of illness (COI) every 3 years from 1996 to 2020 using governmental
statistics. COI was calculated by summing the direct costs, morbidity costs, and
mortality costs. RESULTS: From 1996 to 2011 COI was trending upward. COI in 2011
(697 billion yen) was 1.7-times greater than that in 1996 (407 billion yen). The
mortality costs accounted for approximately 65-70% of the total COI and were a
major contributing factor to increase in COI. It was predicted that COI would
continue to trend upwards until 2020 (699.4-743.8 billion yen depending on the
model), but the rate of increase would decline. CONCLUSIONS: COI of breast cancer
has been steadily increasing since 1996. While the rate of increase is expected
to plateau, the average age at death from breast cancer is still less than that
from other cancers, and the relative economic burden of breast cancer will
continue to increase in the foreseeable future.
PMID- 26438239
TI - Diffuse cortical calcification of failed kidney allograft.
PMID- 26438240
TI - Social inequalities in a population based colorectal cancer screening programme
in the Basque Country.
AB - BACKGROUND: While it is known that a variety of factors (biological, behavioural
and interventional) play a major role in the health of individuals and
populations, the importance of the role of social determinants is less clear. The
effect of social inequality on population-based screening for colorectal cancer
(CRC) could limit the value of such programmes. The present study aims to
determine whether such inequalities exist. METHODS: Data was obtained from the
population-based screening programme administered in the Autonomous Community of
the Basque Country, Spain, with a target population aged 50 to 69, first invited
to participate between 2009 and 2011. The magnitude of inequality was analysed
using the odds ratio (taking the least disadvantaged socioeconomic quintile as
the reference population), the population attributable risk and the relative
index of inequality, based on the regression, which is the ratio of the rates in
the most and least disadvantaged socioeconomic groups. RESULTS: The target
population comprised 242,394 people, with the test kit successfully sent to 95.1
% (230,510). The overall response rate was 64.3 % (67.1 in women and 61.4 % men).
Among women, the highest participation was in the third quintile (71.5 %) and the
lowest in the first - the least disadvantaged (65.7 %). The lowest and highest
rates of people with identified lesions were in the second and fourth quintiles
(14.7/1000 and 17.0/1000 respectively). Among men, the response rate was lowest
in the fifth - most disadvantaged - quintile (60.2 %). The highest rate of
identified lesions was in the fifth quintile; 38 % higher than the first
(55.7/1000 compared to 41.0/1000). CONCLUSIONS: Sex and socioeconomic group
influence the rate of participation in the CRC programme and the rate of lesions
found in the participants. Any public health programme is morally and ethically
obliged to strive for equity and effectiveness. Improving participation of men
and socially disadvantaged groups should be taken in account.
PMID- 26438241
TI - The Overwhelming Majority but not All Motor Fibers of the Bifid Recurrent
Laryngeal Nerve are Located in the Anterior Extralaryngeal Branch.
AB - BACKGROUND: Few small studies reported that motor fibers are located exclusively
in the anterior branch of the bifid recurrent laryngeal nerve (RLN). The aim of
this study was to investigate the location of the motor fibers to the intrinsic
muscles of the larynx among the bifid RLNs, and assess the prevalence of RLN
injury with respect to nerve branching in a pragmatic trial. METHODS: This was a
prospective cohort study of 1250 patients who underwent total thyroidectomy with
intraoperative neural monitoring. The primary outcome was the position of the
motor fibers in the bifid nerves. Adduction of the vocal folds was detected by
the endotracheal tube electromyography and abduction by finger palpation of
muscle contraction in the posterior cricoarytenoid. The secondary outcomes were
the prevalence of the RLN branching and the prevalence of RLN injury in bifid
versus non-bifid nerves. RESULTS: The bifid RLNs were identified in 613/2500
(24.5%) nerves at risk, including 92 (7.4%) patients with bilateral bifurcations.
The motor fibers were present exclusively in the anterior branch in 605/613
(98.7%) bifid nerves, and in both the RLN branches in 8/613 (1.3%) bifid nerves.
Prevalence of RLN injury was 5.2 versus 1.6% for the bifid versus non-bifid
nerves (p < 0.001), odds ratio 2.98 (95% confidence interval 1.79-4.95; p <
0.001). CONCLUSIONS: The motor fibers of the RLN are located in the anterior
extralaryngeal branch in the vast majority of but not in all patients. In rare
cases, the motor fibers for adduction or abduction are located in the posterior
branch of the RLN. As the bifid nerves are more prone to injury than non-branched
nerves, meticulous dissection is recommended to assure preservation of all the
branches of the RLN during thyroidectomy.
PMID- 26438242
TI - Genotype-Phenotype Correlation in Indian Patients with MEN2-Associated
Pheochromocytoma and Comparison of Clinico-Pathological Attributes with
Apparently Sporadic Adrenal Pheochromocytoma.
AB - INTRODUCTION: Pheochromocytoma (PCC) manifests in up to 50% of MEN2 patients. We
correlated the clinico-pathological features of MEN2-associated PCC (MEN-PCC)
with RET mutations and compared them with non-MEN adrenal-PCCs. METHODS: In this
retrospective single institution study on a large PCC database (n = 208, 1997
2014) 24 MEN-PCC patients with known RET mutations were reviewed. Excluding 7
with incomplete data, the study cohort of 17 MEN-PCC patients from 11 kindreds
(M:F::7:10) was identified. Clinical, biochemical, pathological attributes, and
outcomes in the MEN-PCC group were correlated with the genotype, and further
compared with non-MEN, apparently sporadic adrenal-PCCs (n = 132, excluding 37
extra-adrenal and 15 VHL/NF1/SDH-associated PCC). RESULTS: Components of MEN2
encountered included MTC in 13(76.5%), Marfanoid habitus in 2, and PHPT,
cutaneous lichen amyloidosis and mucosal neuromas in 1 patient each. In
11(64.7%), PCC was the first detected MEN2 component (Symptomatic:8,
Incidentaloma:3). Four (23.5%) were normotensive; 8(47.1%) had bilateral PCC (7
synchronous, 1 metachronous). Surgery for PCC included laparoscopic adrenalectomy
in 12; and cortical-sparing adrenalectomy in 2 of 8 bilateral PCC patients. Mean
MEN-PCC tumor size was 6.9 +/- 3.9 cm, and 6(35%) had additional adrenal
medullary hyperplasia. Four different genotypes were encountered, commonest
involving codon 634, others being 804 and 918. Mean age in MEN-PCC (27.7 +/- 12.2
years) was lower than non-MEN PCC (39.4 +/- 15.7, p = 0.018). Proportion of
pediatric patients (35.3% in MEN-PCC vs. 12.9% in non-MEN-PCC, p = 0.007),
bilateral tumors (47.1% in MEN-PCC, 4.5% in non-MEN-PCC, p < 0.001), and adrenal
medullary hyperplasia (35.2% in MEN-PCC, 0.7% in non-MEN-PCC, p < 0.001) were
different. Median 24-hour urinary metanephrines was significantly higher in index
MEN-PCC patients, than non-MEN-PCC (634 vs. 214 mcg/24 h, p value = 0.006), but
was non-significantly higher in non-index MEN-PCC patients. Mean tumor sizes were
comparable in the two groups. None of MEN-PCC patients had malignant PCC,
compared to 7(5.3%) in non-MEN-PCC. CONCLUSIONS: In this cohort of MEN-PCC from
India, the commonest causative RET mutations for MEN-PCC involved codon 634. MEN
PCC patients were younger, and more frequently had bilateral PCC than non-MEN
disease. MEN-PCC patients in India are diagnosed with large tumors and extremely
high catecholamine/metanephrine levels.
PMID- 26438243
TI - A particular silent codon exchange in a recombinant gene greatly influences host
cell metabolic activity.
AB - BACKGROUND: Recombinant protein production using Escherichia coli as expression
host is highly efficient, however, it also induces strong host cell metabolic
burden. Energy and biomass precursors are withdrawn from the host's metabolism as
they are required for plasmid replication, heterologous gene expression and
protein production. Rare codons in a heterologous gene may be a further drawback.
This study aims to investigate the influence of particular silent codon exchanges
within a heterologous gene on host cell metabolic activity. Silent mutations were
introduced into the coding sequence of a model protein to introduce all
synonymous arginine or leucine codons at two randomly defined positions, as well
as substitutions leading to identical amino acid exchanges with different
synonymous codons. The respective E. coli clones were compared during cultivation
in a mineral autoinduction medium using specialized online and offline measuring
techniques to quantitatively analyze effects on respiration, biomass and protein
production, as well as on carbon source consumption, plasmid copy number,
intracellular nucleobases and mRNA content of each clone. RESULTS: Host stain
metabolic burden correlates with recombinant protein production. Upon
heterologous gene expression, tremendous differences in respiration, biomass and
protein production were observed. According to their different respiration
activity the E. coli clones could be classified into two groups, Type A and Type
B. Type A clones tended to higher product formation, Type B clones showed
stronger biomass formation. Whereas codon usage and intracellular nucleobases had
no influence on the Type-A-Type-B-behavior, plasmid copy number, mRNA content and
carbon source consumption strongly differed between the two groups. CONCLUSIONS:
Particular silent codon exchanges in a heterologous gene sequence led to
differences in initial growth of Type A and Type B clones. Thus, the biomass
concentration at the time point of induction varied. In consequence, not only
plasmid copy number and expression levels differed between the two groups, but
also the kinetics of lactose and glycerol consumption. Even though the underlying
molecular mechanisms are not yet identified we observed the astonishing
phenomenon that particular silent codon exchanges within a heterologous gene
tremendously affect host cell metabolism and recombinant protein production. This
could have great impact on codon optimization of heterologous genes, screening
procedures for improved variants, and biotechnological protein production
processes.
PMID- 26438244
TI - Unraveling the evolution and regulation of the alternative oxidase gene family in
plants.
AB - Alternative oxidase (AOX) is a diiron carboxylate protein present in all plants
examined to date that couples the oxidation of ubiquinol with the reduction of
oxygen to water. The predominant structure of AOX genes is four exons interrupted
by three introns. In this study, by analyzing the genomic sequences of genes from
different plant species, we deduced that intron/exon loss/gain and deletion of
fragments are the major mechanisms responsible for the generation and evolution
of AOX paralogous genes. Integrating gene duplication and structural information
with expression profiles for various AOXs revealed that tandem duplication/block
duplication contributed greatly to the generation and maintenance of the AOX gene
family. Notably, the expression profiles based on public microarray database
showed highly diverse expression patterns among AOX members in different
developmental stages and tissues and that both orthologous and paralogous genes
did not have the same expression profiles due to their divergence in regulatory
regions. Comparative analysis of genes in six plant species under various
perturbations indicated a large number of protein kinases, transcription factors
and antioxidant enzymes are co-expressed with AOX. Of these, four sets of
transcription factors--WRKY, NAC, bZIP and MYB--are likely involved in the
regulating the differential responses of AOX1 genes to specific stresses.
Furthermore, divergence of AOX1 and AOX2 subfamilies in regulation might be the
main reason for their differential stress responses.
PMID- 26438245
TI - Osteotomy configuration of the proximal wedge and analysis of the affecting
factors in the medial open-wedge high tibial osteotomy.
AB - PURPOSE: The purposes of this study were (1) to confirm the disparity of the
measured thickness at the lateral hinge between anterior-posterior (AP)
radiograph and 3D CT image, (2) to evaluate the affecting factors, and (3) to
evaluate the differences between uniplanar and biplanar osteotomies. METHODS:
From 2012 to 2014, a prospective comparative study was performed with 30 patients
who received uniplanar osteotomy (group I) and 35 patients who received biplanar
osteotomy (group II). For measurement of the proximal wedge, postoperative AP
radiograph and 3D CT images were used. In the AP radiograph, medial and lateral
bony bridge thicknesses were measured. In the 3D CT, the anterior and posterior
images parallel to the coronal plane were selected for the evaluation. Coronal
osteotomy slope was measured with the anterior image of the 3D CT scan. Sagittal
osteotomy slope was measured with the sagittal section of the CT scan. RESULTS:
Differences between the lateral bony bridge thicknesses measured in AP radiograph
and the posterolateral posterolateral bony bridge thicknesses measured in 3D CT
were statistically significant in both groups. Negative correlation was observed
in the biplanar osteotomy group. Differences of the sagittal osteotomy slope from
the native tibial slope showed negative correlation in the biplanar osteotomy
group. CONCLUSION: Thickness of the posterolateral bony bridge was smaller
compared to the observed thickness on the AP radiograph image that is routinely
used for the follow-up. The thickness would be getting smaller if osteotomy is
performed with an abrupt angle on the coronal plane and reverse slope on the
sagittal plane. Therefore, osteotomy with abrupt angle on the coronal plane and
reverse slope on the sagittal plane should be avoided for the proper thickness of
the posterolateral bony bridge. LEVEL OF EVIDENCE: III.
PMID- 26438246
TI - Changes in the orientation of knee functional flexion axis during passive flexion
and extension movements in navigated total knee arthroplasty.
AB - PURPOSE: Recently, the functional flexion axis has been considered to provide a
proper rotational alignment of the femoral component in total knee arthroplasty.
Several factors could influence the identification of the functional flexion
axis. The purpose of this study was to analyse the estimation of the functional
flexion axis by separately focusing on passive flexion and extension movements
and specifically assessing its orientation compared to the transepicondylar axis,
in both the axial plane and the frontal plane. METHODS: Anatomical and kinematic
acquisitions were performed using a commercial navigation system on 79 patients
undergoing total knee arthroplasty with cruciate substituting prosthesis design.
The functional flexion axis was estimated from passive movements, between 0
degrees and 120 degrees of flexion and back. Intra-observer agreement and
reliability, internal-external rotation and the angle with the surgical
transepicondylar axis, in axial and frontal planes, were separately analysed for
flexion and extension, in pre- and post-implant conditions. RESULTS: The analysis
of reliability and agreement showed good results. The identification of the
functional flexion axis showed statistically significant differences both in
relation to flexion and extension and to pre- and post-implant conditions, both
in frontal plane and in axial plane. The analysis of internal-external rotation
confirmed these differences in kinematics (p < 0.05, between 25 degrees and 35
degrees of flexion). CONCLUSIONS: The identification of the functional flexion
axis changed in relation to passive flexion and extension movements, above all in
frontal plane, while it resulted more stable and reliable in axial plane. These
findings supported the possible clinical application of the functional flexion
axis in the surgical practice by implementing navigated procedures. However,
further analyses are required to better understand the factors affecting the
identification of the functional flexion axis. LEVEL OF EVIDENCE: IV.
PMID- 26438247
TI - Return to sport following acute lateral ligament repair of the ankle in
professional athletes.
AB - PURPOSE: Recent literature supports early reconstruction of severe acute lateral
ligament injuries in professional athletes, suggesting earlier rehabilitation and
reduced recurrent instability incidence. Not previously reported, predicting the
time to return to training and play is important to both athlete and club. We
evaluate the effectiveness and complications of lateral ligament reconstruction
in professional athletes. We aim to estimate the time to return to training and
sports in both isolated injuries and patients with additional injuries. METHODS:
A consecutive series of 42 athletes underwent modified Brostrom repair for
clinically and radiologically confirmed acute grade III lateral ligament injury.
Of 42, 30 had isolated complete rupture of ATFL and CFL. Of 42, 12 had additional
injuries (osteochondral lesions, deltoid ligament injuries). All patients
received minimum of 2 years post-operative assessment. RESULTS: The median return
to training and sports for isolated injuries was 63 days (49-110) and 77 days (56
127), respectively. However, for concomitant injury results were 86 days (63-152)
and 105 days (82-178). This delay was significant (p < 0.001). Despite no
difference in pre- and post-op VAS scores between the groups, those with combined
injuries had significantly lower FAOS pain and symptoms sub-scores post
operatively (p = 0.027, p < 0.001). Two superficial infections responded to oral
antibiotics. No patient developed recurrent instability. All returned to their
pre-injury level of professional sports. CONCLUSION: Lateral ligament
reconstruction is a safe and effective treatment for acute severe ruptures
providing a stable ankle and expected return to sports at approximately 10 weeks.
Despite return to the same level of competition, club and player should be aware
that associated injuries may delay return and symptoms may continue. These
results may act as a guide to predict the expected time to return to training and
to sport after surgical repair of acute injuries and also the influence of
associated injuries in prolonging rehabilitation. LEVEL OF EVIDENCE: III.
PMID- 26438248
TI - Engineering Nanomedicines to Overcome Multidrug Resistance in Cancer Therapy.
AB - Drug resistance to conventional antitumor drugs represents one of the major
causes of treatment failure in patients affected by tumors. Two main types of
drug resistance to anticancer drugs are found in tumors, namely intrinsic
resistance, in which tumor cells are inherently resistant to chemotherapy, and
acquired resistance, which results from previous drug exposure. Tumor cells
resistant to a chemotherapeutic agent become cross-resistant to both similar and
structurally unrelated classes of antitumor drugs, a biological mechanism known
as multi drug resistance (MDR). Among the strategies considered to overcome MDR,
nanovector-mediated drug administration represents an innovative and promising
alternative. In this review, we report a number of nanovectors including polymer
drug conjugates, polymeric micelles, nanotubes, LbL nanocapsules, and silica and
gold nanoparticles. These systems are designed for the efficient delivery of
anthracyclines, vinca alkaloids, taxanes, and others drugs. The development of
these nanovectos to specifically overcome MDR and their mechanisms of action are
covered and discussed. Finally, we discuss challenges and opportunities for
further development of nanodevices-based chemotherapies to circumvent MDR through
the design of nanovectors for the delivery of multiple cargoes.
PMID- 26438249
TI - A Review of Bisindolylmethane as an Important Scaffold for Drug Discovery.
AB - Bisindolylmethane and its derivatives are pharmacologically active and applicable
in the field of pharmaceutical chemistry. Bisindolylmethanes have a variety of
biological activities such as antihyperglycemic, antiinflammatory, antibacterial,
anticancer, and antileishmanial activities, including enzyme inhibition activity.
They play a crucial role in many diseases especially anticancer activity.
Modifying their structure had proven to be useful in the search of new
therapeutic agents. Extensive research carried out on bisindolylmethane and its
derivatives shows that they are pharmacologically significant. The present review
focuses on the pharmacological profile of bisindolylmethane derivatives. This
review includes the current literature with an update of research findings as
well as the perspectives that they hold for future research.
PMID- 26438250
TI - Biological and chemical diversity of coral-derived microorganisms.
AB - Coral-derived microorganisms have been a major focus of many research efforts on
marine ecology in recent decades. Importantly, research on bioactive compounds
from these diverse microorganisms, which include fungi and bacteria, has
experienced an explosive growth during the past five years. This has unveiled the
ecological roles of these microorganisms, which prevent antifouling, inhibit
pathogenic bacteria, and deter predators in ocean ecosystems. Moreover, the
structural diversity and pharmacological activity of the compounds produced by
these microorganisms have also been studied extensively, leading not only to an
understanding their roles within ecosystems, but also the potential value of
their use in human health. In this review, 258 marine natural products, including
polyketides, terpenoids, meroterpenoids, alkaloids, peptides, shikimates and
lipids, all discovered in the past 24 years, are presented. 146 references are
cited.
PMID- 26438251
TI - ROS1 Kinase Inhibitors for Molecular-Targeted Therapies.
AB - ROS1 is a pivotal transmembrane receptor protein tyrosine kinase which regulates
several cellular processes like apoptosis, survival, differentiation,
proliferation, cell migration, and transformation. There is increasing evidence
supporting that ROS1 plays an important role in different malignancies including
glioblastoma, colorectal cancer, gastric adenocarcinoma, inflammatory
myofibroblastic tumor, ovarian cancer, angiosarcoma, and non small cell lung
cancer; thus, ROS1 has become a potential drug discovery target. ROS1 shares
about 49% sequence homology with ALK primary structure; therefore, wide range of
ALK kinase inhibitors have shown in vitro inhibitory activity against ROS1
kinase. After Crizotinib approval by FDA for the management of ALK-rearranged
lung cancer, ROS1-positive tumors have been focused. Although significant
advancements have been achieved in understanding ROS1 function and its signaling
pathways plus recent discovery of small molecules modulating ROS1 protein, a
vital need of medicinal chemistry efforts is still required to produce selective
and potent ROS1 inhibitors as an important therapeutic strategy for different
human malignancies. This review focuses on the current knowledge about different
scaffolds targeting ROS1 rearrangements, methods to synthesis, and some
biological data about the most potent compounds that have delivered various
scaffold structures.
PMID- 26438252
TI - Diagnostic accuracy of WHO verbal autopsy tool for ascertaining causes of
neonatal deaths in the urban setting of Pakistan: a hospital-based prospective
study.
AB - BACKGROUND: Globally, clinical certification of the cause of neonatal death is
not commonly available in developing countries. Under such circumstances it is
imperative to use available WHO verbal autopsy tool to ascertain causes of death
for strategic health planning in countries where resources are limited and the
burden of neonatal death is high. The study explores the diagnostic accuracy of
WHO revised verbal autopsy tool for ascertaining the causes of neonatal deaths
against reference standard diagnosis obtained from standardized clinical and
supportive hospital data. METHODS: All neonatal deaths were recruited between
August 2006 -February 2008 from two tertiary teaching hospitals in Province
Sindh, Pakistan. The reference standard cause of death was established by two
senior pediatricians within 2 days of occurrence of death using the International
Cause of Death coding system. For verbal autopsy, trained female community health
worker interviewed mother or care taker of the deceased within 2-6 weeks of death
using a modified WHO verbal autopsy tool. Cause of death was assigned by 2
trained pediatricians. The performance was assessed in terms of sensitivity and
specificity. RESULTS: Out of 626 neonatal deaths, cause-specific mortality
fractions for neonatal deaths were almost similar in both verbal autopsy and
reference standard diagnosis. Sensitivity of verbal autopsy was more than 93% for
diagnosing prematurity and 83.5% for birth asphyxia. However the verbal autopsy
didn't have acceptable accuracy for diagnosing the congenital malformation 57%.
The specificity for all five major causes of neonatal deaths was greater than
90%. CONCLUSION: The WHO revised verbal autopsy tool had reasonable validity in
determining causes of neonatal deaths. The tool can be used in resource limited
community-based settings where neonatal mortality rate is high and death
certificates from hospitals are not available.
PMID- 26438253
TI - Turn of the screw--helicases everywhere.
PMID- 26438254
TI - Does learning to read shape verbal working memory?
AB - Many experimental studies have investigated the relationship between the
acquisition of reading and working memory in a unidirectional way, attempting to
determine to what extent individual differences in working memory can predict
reading achievement. In contrast, very little attention has been dedicated to the
converse possibility that learning to read shapes the development of verbal
memory processes. In this paper, we present available evidence that advocates a
more prominent role for reading acquisition on verbal working memory and then
discuss the potential mechanisms of such literacy effects. First, the early
decoding activities might bolster the development of subvocal rehearsal, which,
in turn, would enhance serial order performance in immediate memory tasks. In
addition, learning to read and write in an alphabetical system allows the
emergence of phonemic awareness and finely tuned phonological representations, as
well as of orthographic representations. This could improve the quality,
strength, and precision of lexical representations, and hence offer better
support for the temporary encoding of memory items and/or for their retrieval.
PMID- 26438256
TI - Erratum to: Symptom attributions in patients with colorectal cancer.
PMID- 26438255
TI - Re-examining selective adaptation: Fatiguing feature detectors, or distributional
learning?
AB - When a listener hears many good examples of a /b/ in a row, they are less likely
to classify other sounds on, e.g., a /b/-to-/d/ continuum as /b/. This phenomenon
is known as selective adaptation and is a well-studied property of speech
perception. Traditionally, selective adaptation is seen as a mechanistic property
of the speech perception system, and attributed to fatigue in acoustic-phonetic
feature detectors. However, recent developments in our understanding of non
linguistic sensory adaptation and higher-level adaptive plasticity in speech
perception and language comprehension suggest that it is time to re-visit the
phenomenon of selective adaptation. We argue that selective adaptation is better
thought of as a computational property of the speech perception system. Drawing
on a common thread in recent work on both non-linguistic sensory adaptation and
plasticity in language comprehension, we furthermore propose that selective
adaptation can be seen as a consequence of distributional learning across
multiple levels of representation. This proposal opens up new questions for
research on selective adaptation itself, and also suggests that selective
adaptation can be an important bridge between work on adaptation in low-level
sensory systems and the complicated plasticity of the adult language
comprehension system.
PMID- 26438257
TI - Circulating concentration of markers of angiogenic activity in patients with
sarcoidosis and idiopathic pulmonary fibrosis.
AB - BACKGROUND: Angiogenesis is an important process involved in the pathogenesis of
diffuse parenchymal lung diseases. The aim of the study was to compare the
angiogenic profile of patients with sarcoidosis and idiopathic pulmonary fibrosis
(IPF) based on analysis of circulating factors. METHODS: Serum concentrations of
angiopoietin-2 (Ang-2), follistatin, granulocyte-macrophage-colony stimulating
factor (GM-CSF), interleukin-8 (IL-8), platelet derived growth factor-BB (PDGF
BB), platelet endothelial cellular adhesion molecule-1 (PECAM-1) and vascular
endothelial growth factors (VEGF) were measured in the patients and the healthy
subjects. RESULTS: Serum concentrations of G-CSF, follistatin, PECAM-1 and IL-8
were significantly higher in the IPF patients in comparison with the control
group and the sarcoid patients. PDGF-BB concentrations were also significantly
higher in serum of IPF patients than in sarcoid patients, but not than in the
controls. In contrast, Ang-2 and VEGF concentrations did not differ significantly
between the three groups. In the sarcoid patients, irrespective of the disease
activity or the radiological stage, serum concentrations of these cytokines were
similar to the control group. CONCLUSIONS: These results indicate that
differences may exist in angiogenic activity between patients with parenchymal
lung diseases. In contrast to sarcoidosis, IPF is characterized by a higher serum
concentration of different molecules involved in the angiogenic processes .
PMID- 26438258
TI - The pla gene, encoding plasminogen activator, is not specific to Yersinia pestis.
AB - Here we present evidence to show that the pla gene, previously thought to be
specific to Yersinia pestis, occurs in some strains of Citrobacter koseri and
Escherichia coli. This means that detection of this gene on its own can no longer
be taken as evidence of detection of Y. pestis.
PMID- 26438259
TI - Membrane Hydration: A Hint to a New Model for Biomembranes.
AB - The classical view of a biological membrane is based on the Singer-Nicholson
mosaic fluid model in which the lipid bilayer is the structural backbone. Under
this paradigm, many studies of biological processes such as, permeability, active
transport, enzyme activity and adhesion and fusion processes have been
rationalized considering the lipid membrane as a low dielectric slab of
hydrocarbon chains with polar head groups exposed to water at each side in which
oil/water partition prevails. In spite of several analyses and evidence available
in relation to membrane hydration, water is not taken into account as a
functional component. For this purpose, new insights in the water organization in
restricted environments and the thermodynamical and mechanical properties
emerging from them are specifically analysed and correlated.This chapter
summarizes the progress of the studies of water in membranes along the book in
order to give a more realistic structural and dynamical picture accounting for
the membrane functional properties.
PMID- 26438260
TI - Use of X-Ray and Neutron Scattering Methods with Volume Measurements to Determine
Lipid Bilayer Structure and Number of Water Molecules/Lipid.
AB - In this chapter I begin with a historical perspective of membrane models,
starting in the early twentieth century. As these membrane models evolved, so did
experiments to characterize the structure and water content of purified lipid
bilayers. The wide-spread use of the X-ray gravimetric, or Luzzati method, is
critically discussed. The main motivation of the gravimetric technique is to
determine the number of water molecules/lipid, n(W), and then derive other
important structural quantities, such as area/lipid, A(L). Subsequent experiments
from the Nagle/Tristram-Nagle laboratory using X-ray and neutron scattering,
first determine A(L) and then calculate n(W), using molecular lipid V(L) and
water V(W) volumes. This chapter describes the details of our volume experiments
to carefully measure V(L). Our results also determine n(W)', the steric water
associated with the lipid headgroup, and how our calculated value compares to
many literature values of tightly-associated headgroup water.
PMID- 26438261
TI - Water and Lipid Bilayers.
AB - Water is crucial to the structure and function of biological membranes. In fact,
the membrane's basic structural unit, i.e. the lipid bilayer, is self-assembled
and stabilized by the so-called hydrophobic effect, whereby lipid molecules
unable to hydrogen bond with water aggregate in order to prevent their
hydrophobic portions from being exposed to water. However, this is just the
beginning of the lipid-bilayer-water relationship. This mutual interaction
defines vesicle stability in solution, controls small molecule permeation, and
defines the spacing between lamella in multi-lamellar systems, to name a few
examples. This chapter will describe the structural and dynamical properties
central to these, and other water- lipid bilayer interactions.
PMID- 26438262
TI - Hydration Forces Between Lipid Bilayers: A Theoretical Overview and a Look on
Methods Exploring Dehydration.
AB - Although, many biological systems fulfil their functions under the condition of
excess hydration, the behaviour of bound water as well as the processes
accompanying dehydration are nevertheless important to investigate. Dehydration
can be a result of applied mechanical pressure, lowered humidity or cryogenic
conditions. The effort required to dehydrate a lipid membrane at relatively low
degree of hydration can be described by a disjoining pressure which is called
hydration pressure or hydration force. This force is short-ranging (a few nm) and
is usually considered to be independent of other surface forces, such as ionic or
undulation forces. Different theories were developed to explain hydration forces
that are usually not consistent with each other and which are also partially in
conflict with experimental or numerical data.Over the last decades it has been
more and more realised that one experimental method alone is not capable of
providing much new insight into the world of such hydration forces. Therefore,
research requires the comparison of results obtained from the different methods.
This chapter thus deals with an overview on the theory of hydration forces,
ranging from polarisation theory to protrusion forces, and presents a selection
of experimental techniques appropriate for their characterisation, such as X-ray
diffraction, atomic force microscopy and even calorimetry.
PMID- 26438263
TI - Monitoring Membrane Hydration with 2-(Dimethylamino)-6-Acylnaphtalenes
Fluorescent Probes.
AB - A family of polarity sensitive fluorescent probes (2-(dimethylamino)-6
acylnaphtalenes, i.e. LAURDAN, PRODAN, ACDAN) was introduced by Gregorio Weber in
1979, with the aim to monitor solvent relaxation phenomena on protein matrices.
In the following years, however, PRODAN and particularly LAURDAN, were used to
study membrane lateral structure and associated dynamics. Once incorporated into
membranes, the (nanosecond) fluorescent decay of these probes is strongly
affected by changes in the local polarity and relaxation dynamics of restricted
water molecules existing at the membrane/water interface. For instance, when
glycerophospholipid containing membranes undertake a solid ordered (gel) to
liquid disordered phase transition the fluorescence emission maximum of these
probes shift ~ 50 nm with a significant change in their fluorescence lifetime.
Furthermore, the fluorescence parameters of LAURDAN and PRODAN are exquisitely
sensitive to cholesterol effects, allowing interpretations that correlate changes
in membrane packing with membrane hydration. Different membrane model systems as
well as innate biological membranes have been studied with this family of probes
allowing interesting comparative studies. This chapter presents a short
historical overview about these fluorescent reporters, discusses on different
models proposed to explain their sensitivity to membrane hydration, and includes
relevant examples from experiments performed in artificial and biological
membranes.
PMID- 26438264
TI - Long-Range Lipid-Water Interaction as Observed by ATR-FTIR Spectroscopy.
AB - It is commonly assumed that the structure of water at a lipid-water interface is
influenced mostly in the first hydration layer. However, recent results from
different experimental methods show that perturbation extends through several
hydration layers. Due to its low light penetration depth, attenuated total
reflection Fourier transform infrared (ATR-FTIR) spectroscopy is specifically
suited to study interlamellar water structure in multibilayers. Results obtained
by this technique confirm the long-range water structure disturbance.
Consequently, in confined membrane environments nearly all water molecules can be
perturbed. It is important to note that the behavior of confined water molecules
differs significantly in samples prepared in excess water and in partially
hydrated samples. We show in what manner the interlamellar water perturbation is
influenced by the hydration level and how it is sequentially modified with a step
by-step dehydration of samples either by water evaporation or by osmotic
pressure. Our results also indicate that besides different levels of hydration
the lipid-water interaction is modulated by different lipid headgroups and
different lipid phases as well. Therefore, modification of interlamellar water
properties may clarify the role of water-mediated effects in biological
processes.
PMID- 26438265
TI - Hydration and Nanoconfined Water: Insights from Computer Simulations.
AB - The comprehension of the structure and behavior of water at interfaces and under
nanoconfinement represents an issue of major concern in several central research
areas like hydration, reaction dynamics and biology. From one side, water is
known to play a dominant role in the structuring, the dynamics and the
functionality of biological molecules, governing main processes like protein
folding, protein binding and biological function. In turn, the same principles
that rule biological organization at the molecular level are also operative for
materials science processes that take place within a water environment, being
responsible for the self-assembly of molecular structures to create synthetic
supramolecular nanometrically-sized materials. Thus, the understanding of the
principles of water hydration, including the development of a theory of
hydrophobicity at the nanoscale, is imperative both from a fundamental and an
applied standpoint. In this work we present some molecular dynamics studies of
the structure and dynamics of water at different interfaces or confinement
conditions, ranging from simple model hydrophobic interfaces with different
geometrical constraints (in order to single out curvature effects), to self
assembled monolayers, proteins and phospholipid membranes. The tendency of the
water molecules to sacrifice the lowest hydrogen bond (HB) coordination as
possible at extended interfaces is revealed. This fact makes the first hydration
layers to be highly oriented, in some situations even resembling the structure of
hexagonal ice. A similar trend to maximize the number of HBs is shown to hold in
cavity filling, with small subnanometric hydrophobic cavities remaining empty
while larger cavities display an alternation of filled and dry states with a
significant inner HB network. We also study interfaces with complex chemical and
geometrical nature in order to determine how different conditions affect the
local hydration properties. Thus, we show some results for protein hydration and,
particularly, some preliminary studies on membrane hydration. Finally,
calculations of a local hydrophobicity measure of relevance for binding and self
assembly are also presented. We then conclude with a few words of further
emphasis on the relevance of this kind of knowledge to biology and to the design
of new materials by highlighting the context-dependent and non-additive nature of
different non-covalent interactions in an aqueous nanoenvironment, an issue that
is usually greatly overlooked.
PMID- 26438266
TI - Aquaphotomics: Near Infrared Spectroscopy and Water States in Biological Systems.
AB - Aquaphotomics is a new discipline that provides a framework for understanding
changes in water molecular system presented as a water spectral pattern, to
mirror the rest of the solution and to give a holistic description related to
system functionality. One of its main purposes is to identify water bands as main
coordinates of future absorbance patterns to be used as a system biomarker. This
chapter presents the Aquaphotomics methodology and illustrates a way to identify
specific water bands using temperature change and addition of solutions of
different ionic strength as perturbations. Rapid and precise measurement of low
concentration solutes has been given as a strong evidence of the vast information
that "the water spectral pattern as molecular mirror" approach provides. Few
applications using near infrared spectroscopy and multivariate analysis as main
tools of Aquaphotomics have been presented.
PMID- 26438267
TI - Hydration in Lipid Monolayers: Correlation of Water Activity and Surface
Pressure.
AB - In order to give a physical meaning to each region of the membrane we define the
interphase as the region in a lipid membrane corresponding to the polar head
groups imbibed in water with net different properties than the hydrocarbon region
and the water phase. The interphase region is analyzed under the scope of
thermodynamics of surface and solutions based on the definition of Defay
Prigogine of an interphase and the derivation that it has in the understanding of
membrane processeses in the context of biological response. In the view of this
approach, the complete monolayer is considered as the lipid layer one molecule
thick plus the bidimensional solution of the polar head groups inherent to it
(the interphase region). Surface water activity appears as a common factor for
the interaction of several aqueous soluble and surface active proteins with lipid
membranes of different composition. Protein perturbation can be measured by
changes in the surface pressure of lipid monolayers at different initial water
surface activities. As predicted by solution chemistry, the increase of surface
pressure is independent of the particle nature that dissolves. Therefore,
membranes give a similar response in terms of the determined surface states given
by water activity independent of the protein or peptide.
PMID- 26438268
TI - Water at Biological Phase Boundaries: Its Role in Interfacial Activation of
Enzymes and Metabolic Pathways.
AB - Many life-sustaining activities in living cells occur at the membrane-water
interface. The pertinent questions that we need to ask are, what are the
evolutionary reasons in biology for choosing the membrane-water interface as the
site for performing and/or controlling crucial biological reactions, and what is
the key physical principle that is very singular to the membrane-water interface
that biology exploits for regulating metabolic processes in cells? In this
chapter, a hypothesis is developed, which espouses that cells control activities
of membrane-bound enzymes through manipulation of the thermodynamic activity of
water in the lipid-water interfacial region. The hypothesis is based on the fact
that the surface pressure of a lipid monolayer is a direct measure of the
thermodynamic activity of water at the lipid-water interface. Accordingly, the
surface pressure-dependent activation or inactivation of interfacial enzymes is
directly related to changes in the thermodynamic activity of interfacial water.
Extension of this argument suggests that cells may manipulate conformations (and
activities) of membrane-bound enzymes by manipulating the (re)activity of
interfacial water at various locations in the membrane by localized compression
or expansion of the interface. In this respect, cells may use the membrane-bound
hormone receptors, lipid phase transition, and local variations in membrane lipid
composition as effectors of local compression and/or expansion of membrane, and
thereby local water activity. Several experimental data in the literature will be
reexamined in the light of this hypothesis.
PMID- 26438269
TI - Anhydrobiosis: An Unsolved Problem with Applications in Human Welfare.
AB - Anhydrobiosis (Life Without Water) has been known for millennia, but the
underlying mechanisms have not been understood until recent decades, and we have
achieved only a partial understanding. One of the chief sites of damage from
dehydration is membranes, and we and others have provided evidence that this
damage may be obviated by the production of certain sugars, particularly
trehalose. The sugar stabilizes membranes by preventing fusion and fluidizing the
dry bilayers. The mechanism by which this is accomplished has been controversial,
and I review that controversy here. In the past decade evidence is accumulating
for a role of stress proteins in addition to or as a substitute for trehalose.
Genomic studies on anhydrobiotes are yielding rapid progress. Also in the past
decade, numerous uses for trehalose in treating human diseases have been
proposed, some of which are in clinical testing. I conclude that the mechanisms
underlying anhydrobiosis are more complex than we thought 20 years ago, but
progress is being made towards elucidating those mechanisms.
PMID- 26438270
TI - Up-regulated S100 calcium binding protein A8 in Plasmodium-infected patients
correlates with CD4(+)CD25(+)Foxp3 regulatory T cell generation.
AB - BACKGROUND: The pro-inflammatory S100 calcium binding protein A8 (S100A8) is
elevated in the serum of patients with Plasmodium falciparum malaria, but its
function in Plasmodium vivax malaria is not yet clear. This function was
investigated in P. vivax-infected patients in this study. METHODS: The level of
S100A8 in the serum was measured with ELISA. Full amino acids of S100A8 were
synthesized to verify the functions for maturation of immature dendritic cell
(iDC) and evaluation of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) generation by
mature DC (mDC). RESULTS: A higher amount of S100A8 was detected in vivax
infected patients (141.2 +/- 61.849 ng/ml, n = 40) compared with normal control
group (48.1 +/- 27.384 ng/ml, n = 40). The level of S100A8 did not coincide with
that of anti-malarial antibody measured by indirect fluorescent antibody test
(IFAT) using parasite-infected red blood cells as antigen. Programmed death
ligand 1 (PD-L1) was up-regulated on the surface of iDCs following treatment with
synthetic S100A8, not with synthetic MSP-1, AMA-1 and CSP, as compared to the
expression seen for non-treated iDCs. The addition of red blood cells of infected
patients to iDCs also elevated their surface expression of CD86. However, the
serum levels of S100A8 decreased with increase in parasitaemia. DCs matured by
sera containing S100A8 generated Treg cells from naive T cells. The ratio of Treg
cells generated was inversely proportional to the concentration of S100A8 in
sera. CONCLUSIONS: Treg cells suppress the activity of cytotoxic T cells, which
kill malaria parasites; therefore, the up-regulation of S100A8 in malaria
patients may contribute to pathogen immune escape or tolerance.
PMID- 26438272
TI - Marked lateral deviation of the phrenic nerve due to variant origin and course of
the thyrocervical trunk: a cadaveric study.
AB - Phrenic nerve impairment can often lead to serious respiratory disorders under
various pathological conditions. During routine dissection of an 88-year-old
Japanese male cadaver, a victim of heart failure, we recognized an extremely rare
variation of the right thyrocervical trunk arising from the subclavian artery
laterally to the anterior scalene muscle. In addition to that, the ipsilateral
phrenic nerve was drawn and displaced remarkably laterad by this vessel. We
examined all of the branches arising from subclavian arteries, phrenic nerves and
diaphragm muscles. The embryological background of this arterial variation is
considered. The marked displacement with prolonged strain had a potential to
cause phrenic nerve impairment with an atrophic change of the diaphragm muscle.
Recently many image diagnostic technologies have been developed and are often
used. However, it is still possible that rare variations like this case may be
overlooked and can only be recognized by intimate regional examination while
keeping these rare variations in mind.
PMID- 26438271
TI - Loss of Afferent Vestibular Input Produces Central Adaptation and Increased Gain
of Vestibular Prosthetic Stimulation.
AB - Implanted vestibular neurostimulators are effective in driving slow phase eye
movements in monkeys and humans. Furthermore, increases in slow phase velocity
and electrically evoked compound action potential (vECAP) amplitudes occur with
increasing current amplitude of electrical stimulation. In intact monkeys,
protracted intermittent stimulation continues to produce robust behavioral
responses and preserved vECAPs. In lesioned monkeys, shorter duration studies
show preserved but with somewhat lower or higher velocity behavioral responses.
It has been proposed that such changes are due to central adaptive changes in the
electrically elicited vestibulo-ocular reflex (VOR). It is equally possible that
these differences are due to changes in the vestibular periphery in response to
activation of the vestibular efferent system. In order to investigate the site of
adaptive change in response to electrical stimulation, we performed transtympanic
gentamicin perfusions to induce rapid changes in vestibular input in monkeys with
long-standing stably functioning vestibular neurostimulators, disambiguating the
effects of implantation from the effects of ototoxic lesion. Gentamicin injection
was effective in producing a large reduction in natural VOR only when it was
performed in the non-implanted ear, suggesting that the implanted ear contributed
little to the natural rotational response before injection. Injection of the
implanted ear produced a reduction in the vECAP responses in that ear, suggesting
that the intact hair cells in the non-functional ipsilateral ear were
successfully lesioned by gentamicin, reducing the efficacy of stimulation in that
ear. Despite this, injection of both ears produced central plastic changes that
resulted in a dramatically increased slow phase velocity nystagmus elicited by
electrical stimulation. These results suggest that loss of vestibular afferent
activity, and a concurrent loss of electrically elicited vestibular input,
produces an increase in the efficacy of a vestibular neurostimulator by eliciting
centrally adapted behavioral responses without concurrent adaptive increase of
galvanic afferent activation in the periphery.
PMID- 26438273
TI - Extension of the frontal sinus into the roof of the optic canal: a cadaveric case
report.
AB - This case reports a bilateral asymmetrical posterior extension of the frontal
sinuses into the orbital roof with an unusual expansion into the roof of the
optic canal in a 55-year-old male cadaver. The posterior extensions of the sinus
were lined by mucoperiosteum and were separated from the underlying orbital
contents and optic nerve by a thin plate of bone. This knowledge of an unusual
anatomic variation of the frontal sinus may help understand better the ocular and
intracranial complications associated with frontal sinus pathologies.
PMID- 26438274
TI - Influence of the renal lower pole anatomy and mid-renal-zone classification in
successful approach to the calices during flexible ureteroscopy.
AB - PURPOSE: The aim of this paper is to analyze if the anatomy type of the collector
system (CS) limits the accessibility of flexible ureteroscopy (FUR) in the lower
pole. METHODS: We analyzed the pyelographies of 51 patients submitted to FUR and
divided the CS into four groups: A1-kidney midzone (KM) drained by minor calices
(Mc) that are dependent on the superior or on the inferior caliceal groups; A2-KM
drained by crossed calices; B1-KM drained by a major caliceal group independent
both of the superior and inferior groups, and B2-KM drained by Mc entering
directly into the renal pelvis. We studied the number of calices, the angle
between the lower infundibulum and renal pelvis, and the angle between the lower
infundibulum and the inferior Mc. With the use of a flexible ureteroscope, the
access attempt was made to all of lower pole calices. Averages were statistically
compared using the ANOVA and Unpaired T test (p < 0.05). RESULTS: We found 14
kidneys of A1 (27.45 %); 4 of A2 (7.84 %); 17 of B1 (33.33 %); and 16 of B2
(31.37 %). The LIP was >90 degrees in 31 kidneys (60.78 %) and between 61
degrees and 90 degrees in 20 kidneys (39.22 %). We did not find angles smaller
than 60 degrees . The group A1 presented 48 Mc and the UF was able to access 42
(87.5 %); the group A2 had 11 Mc and the UF was able to access 7 (63.64 %); the
group B1 had 48 Mc and the UF was able to access 41 (85.42 %) and in group B2 we
observed 41 Mc and the UF could access 35 (85.36 %). There was no statistical
difference in the accessibility between the groups (p = 0.2610). CONCLUSIONS:
Collecting system with kidney midzone drained by crossed calices presented the
lower accessibility rate during FUR.
PMID- 26438275
TI - Plasma copeptin for short term risk stratification in acute pulmonary embolism.
AB - Copeptin (COP) was reported to have prognostic value in various cardiovascular
diseases. We hypothesized that COP levels reflect the severity of acute pulmonary
embolism (PE) and may be useful in prognostic assessment. Plasma COP
concentrations were measured on the Kryptor Compact Plus platform (BRAHMS,
Hennigsdorf, Germany). The study included 107 consecutive patients with diagnosed
acute PE (47 males, 60 females), with median age of 65 years (range 20-88). High
risk PE was diagnosed in 3 patients (2.8 %), intermediate risk in 69 (64.5 %),
and low risk PE in 35 (32.7 %) patients. Control group included 64 subjects (25
males, 39 females; median age 52.5 year, range 17-87). Four patients (3.7 %) died
during 30-day observation. Complicated clinical course (CCC) was experienced by
10 (9.3 %) patients. COP level was higher in PE patients than in controls [11.55
pmol/L (5.16-87.97), and 19.00 pmol/L (5.51-351.90), respectively, p < 0.0001],
and reflected PE severity. COP plasma concentration in low risk PE was 14.67
nmol/L (5.51-59.61) and in intermediate/high risk PE 19.84 mol/L (5.64-351.90) p
< 0.05. Median COP levels in nonsurvivors was higher than in survivors, 84.6
(28.48-351.9) pmol/L and 18.68 (5.512-210.1) pmol/L, respectively, p = 0.009.
Subjects with CCC presented higher COP levels than patients with benign clinical
course 53.1 (17.95-351.9) pmol/L and 18.16 (5.51-210.1) pmol/L, respectively, p =
0.001. Log-transformed plasma COP was the significant predictor of CCC, OR 16.5
95 % CI 23.2-111.9, p < 0.001. AUC-for prediction of CCC using plasma COP was
0.811 (95 % CI 0.676-0.927). The COP cut off value of 17.95 nmol/l had
sensitivity of 100 %, specificity 49.5 %, positive predictive value of 16.9 % and
negative predictive value of 100 %. We conclude that plasma COP levels can be
regarded for promising marker of severity of acute PE and show potential in risk
stratification of these patients.
PMID- 26438277
TI - Feedbacks on climate in the Earth system: introduction.
PMID- 26438276
TI - A simplified, data-constrained approach to estimate the permafrost carbon-climate
feedback.
AB - We present an approach to estimate the feedback from large-scale thawing of
permafrost soils using a simplified, data-constrained model that combines three
elements: soil carbon (C) maps and profiles to identify the distribution and type
of C in permafrost soils; incubation experiments to quantify the rates of C lost
after thaw; and models of soil thermal dynamics in response to climate warming.
We call the approach the Permafrost Carbon Network Incubation-Panarctic Thermal
scaling approach (PInc-PanTher). The approach assumes that C stocks do not
decompose at all when frozen, but once thawed follow set decomposition
trajectories as a function of soil temperature. The trajectories are determined
according to a three-pool decomposition model fitted to incubation data using
parameters specific to soil horizon types. We calculate litterfall C inputs
required to maintain steady-state C balance for the current climate, and hold
those inputs constant. Soil temperatures are taken from the soil thermal modules
of ecosystem model simulations forced by a common set of future climate change
anomalies under two warming scenarios over the period 2010 to 2100. Under a
medium warming scenario (RCP4.5), the approach projects permafrost soil C losses
of 12.2-33.4 Pg C; under a high warming scenario (RCP8.5), the approach projects
C losses of 27.9-112.6 Pg C. Projected C losses are roughly linearly proportional
to global temperature changes across the two scenarios. These results indicate a
global sensitivity of frozen soil C to climate change (gamma sensitivity) of -14
to -19 Pg C degrees C(-1) on a 100 year time scale. For CH4 emissions, our
approach assumes a fixed saturated area and that increases in CH4 emissions are
related to increased heterotrophic respiration in anoxic soil, yielding CH4
emission increases of 7% and 35% for the RCP4.5 and RCP8.5 scenarios,
respectively, which add an additional greenhouse gas forcing of approximately 10
18%. The simplified approach presented here neglects many important processes
that may amplify or mitigate C release from permafrost soils, but serves as a
data-constrained estimate on the forced, large-scale permafrost C response to
warming.
PMID- 26438279
TI - The inconstancy of the transient climate response parameter under increasing CO2.
AB - In the Coupled Model Intercomparison Project Phase 5 (CMIP5), the model-mean
increase in global mean surface air temperature T under the 1pctCO2 scenario
(atmospheric CO(2) increasing at 1% yr(-1)) during the second doubling of CO(2)
is 40% larger than the transient climate response (TCR), i.e. the increase in T
during the first doubling. We identify four possible contributory effects. First,
the surface climate system loses heat less readily into the ocean beneath as the
latter warms. The model spread in the thermal coupling between the upper and deep
ocean largely explains the model spread in ocean heat uptake efficiency. Second,
CO(2) radiative forcing may rise more rapidly than logarithmically with CO(2)
concentration. Third, the climate feedback parameter may decline as the CO(2)
concentration rises. With CMIP5 data, we cannot distinguish the second and third
possibilities. Fourth, the climate feedback parameter declines as time passes or
T rises; in 1pctCO2, this effect is less important than the others. We find that
T projected for the end of the twenty-first century correlates more highly with T
at the time of quadrupled CO(2) in 1pctCO2 than with the TCR, and we suggest that
the TCR may be underestimated from observed climate change.
PMID- 26438278
TI - The impact of parametrized convection on cloud feedback.
AB - We investigate the sensitivity of cloud feedbacks to the use of convective
parametrizations by repeating the CMIP5/CFMIP-2 AMIP/AMIP + 4K uniform sea
surface temperature perturbation experiments with 10 climate models which have
had their convective parametrizations turned off. Previous studies have suggested
that differences between parametrized convection schemes are a leading source of
inter-model spread in cloud feedbacks. We find however that 'ConvOff' models with
convection switched off have a similar overall range of cloud feedbacks compared
with the standard configurations. Furthermore, applying a simple bias correction
method to allow for differences in present-day global cloud radiative effects
substantially reduces the differences between the cloud feedbacks with and
without parametrized convection in the individual models. We conclude that, while
parametrized convection influences the strength of the cloud feedbacks
substantially in some models, other processes must also contribute substantially
to the overall inter-model spread. The positive shortwave cloud feedbacks seen in
the models in subtropical regimes associated with shallow clouds are still
present in the ConvOff experiments. Inter-model spread in shortwave cloud
feedback increases slightly in regimes associated with trade cumulus in the
ConvOff experiments but is quite similar in the most stable subtropical regimes
associated with stratocumulus clouds. Inter-model spread in longwave cloud
feedbacks in strongly precipitating regions of the tropics is substantially
reduced in the ConvOff experiments however, indicating a considerable local
contribution from differences in the details of convective parametrizations. In
both standard and ConvOff experiments, models with less mid-level cloud and less
moist static energy near the top of the boundary layer tend to have more positive
tropical cloud feedbacks. The role of non-convective processes in contributing to
inter-model spread in cloud feedback is discussed.
PMID- 26438280
TI - Insights into low-latitude cloud feedbacks from high-resolution models.
AB - Cloud feedbacks are a leading source of uncertainty in the climate sensitivity
simulated by global climate models (GCMs). Low-latitude boundary-layer and
cumulus cloud regimes are particularly problematic, because they are sustained by
tight interactions between clouds and unresolved turbulent circulations.
Turbulence-resolving models better simulate such cloud regimes and support the
GCM consensus that they contribute to positive global cloud feedbacks. Large-eddy
simulations using sub-100 m grid spacings over small computational domains
elucidate marine boundary-layer cloud response to greenhouse warming. Four
observationally supported mechanisms contribute: 'thermodynamic' cloudiness
reduction from warming of the atmosphere-ocean column, 'radiative' cloudiness
reduction from CO2- and H2O-induced increase in atmospheric emissivity aloft,
'stability-induced' cloud increase from increased lower tropospheric
stratification, and 'dynamical' cloudiness increase from reduced subsidence. The
cloudiness reduction mechanisms typically dominate, giving positive shortwave
cloud feedback. Cloud-resolving models with horizontal grid spacings of a few
kilometres illuminate how cumulonimbus cloud systems affect climate feedbacks.
Limited-area simulations and superparameterized GCMs show upward shift and slight
reduction of cloud cover in a warmer climate, implying positive cloud feedbacks.
A global cloud-resolving model suggests tropical cirrus increases in a warmer
climate, producing positive longwave cloud feedback, but results are sensitive to
subgrid turbulence and ice microphysics schemes.
PMID- 26438281
TI - Shortwave forcing and feedbacks in Last Glacial Maximum and Mid-Holocene PMIP3
simulations.
AB - Simulations of the climates of the Last Glacial Maximum (LGM), 21 000 years ago,
and of the Mid-Holocene (MH), 6000 years ago, allow an analysis of climate
feedbacks in climate states that are radically different from today. The analyses
of cloud and surface albedo feedbacks show that the shortwave cloud feedback is a
major driver of differences between model results. Similar behaviours appear when
comparing the LGM and MH simulated changes, highlighting the fingerprint of model
physics. Even though the different feedbacks show similarities between the
different climate periods, the fact that their relative strength differs from one
climate to the other prevents a direct comparison of past and future climate
sensitivity. The land-surface feedback also shows large disparities among models
even though they all produce positive sea-ice and snow feedbacks. Models have
very different sensitivities when considering the vegetation feedback. This
feedback has a regional pattern that differs significantly between models and
depends on their level of complexity and model biases. Analyses of the MH climate
in two versions of the IPSL model provide further indication on the possibilities
to assess the role of model biases and model physics on simulated climate changes
using past climates for which observations can be used to assess the model
results.
PMID- 26438282
TI - What does global mean temperature tell us about local climate?
AB - The subject of climate feedbacks focuses attention on global mean surface air
temperature (GMST) as the key metric of climate change. But what does knowledge
of past and future GMST tell us about the climate of specific regions? In the
context of the ongoing UNFCCC process, this is an important question for policy
makers as well as for scientists. The answer depends on many factors, including
the mechanisms causing changes, the timescale of the changes, and the variables
and regions of interest. This paper provides a review and analysis of the
relationship between changes in GMST and changes in local climate, first in
observational records and then in a range of climate model simulations, which are
used to interpret the observations. The focus is on decadal timescales, which are
of particular interest in relation to recent and near-future anthropogenic
climate change. It is shown that GMST primarily provides information about forced
responses, but that understanding and quantifying internal variability is
essential to projecting climate and climate impacts on regional-to-local scales.
The relationship between local forced responses and GMST is often linear but may
be nonlinear, and can be greatly complicated by competition between different
forcing factors. Climate projections are limited not only by uncertainties in the
signal of climate change but also by uncertainties in the characteristics of real
world internal variability. Finally, it is shown that the relationship between
GMST and local climate provides a simple approach to climate change detection,
and a useful guide to attribution studies.
PMID- 26438283
TI - Weighting climate model projections using observational constraints.
AB - Projected climate change integrates the net response to multiple climate
feedbacks. Whereas existing long-term climate change projections are typically
based on unweighted individual climate model simulations, as observed climate
change intensifies it is increasingly becoming possible to constrain the net
response to feedbacks and hence projected warming directly from observed climate
change. One approach scales simulated future warming based on a fit to
observations over the historical period, but this approach is only accurate for
near-term projections and for scenarios of continuously increasing radiative
forcing. For this reason, the recent Fifth Assessment Report of the
Intergovernmental Panel on Climate Change (IPCC AR5) included such
observationally constrained projections in its assessment of warming to 2035, but
used raw model projections of longer term warming to 2100. Here a simple approach
to weighting model projections based on an observational constraint is proposed
which does not assume a linear relationship between past and future changes. This
approach is used to weight model projections of warming in 2081-2100 relative to
1986-2005 under the Representative Concentration Pathway 4.5 forcing scenario,
based on an observationally constrained estimate of the Transient Climate
Response derived from a detection and attribution analysis. The resulting
observationally constrained 5-95% warming range of 0.8-2.5 K is somewhat lower
than the unweighted range of 1.1-2.6 K reported in the IPCC AR5.
PMID- 26438284
TI - Carbon cycle feedbacks and future climate change.
AB - Climate and carbon cycle are tightly coupled on many timescales, from interannual
to multi-millennial timescales. Observations always evidence a positive feedback,
warming leading to release of carbon to the atmosphere; however, the processes at
play differ depending on the timescales. State-of-the-art Earth System Models now
represent these climate-carbon cycle feedbacks, always simulating a positive
feedback over the twentieth and twenty-first centuries, although with substantial
uncertainty. Recent studies now help to reduce this uncertainty. First, on short
timescales, El Nino years record larger than average atmospheric CO2 growth rate,
with tropical land ecosystems being the main drivers. These climate-carbon cycle
anomalies can be used as emerging constraint on the tropical land carbon response
to future climate change. Second, centennial variability found in last millennium
records can be used to constrain the overall global carbon cycle response to
climatic excursions. These independent methods point to climate-carbon cycle
feedback at the low-end of the Earth System Models range, indicating that these
models overestimate the carbon cycle sensitivity to climate change. These new
findings also help to attribute the historical land and ocean carbon sinks to
increase in atmospheric CO2 and climate change.
PMID- 26438285
TI - Atmospheric and oceanic impacts of Antarctic glaciation across the Eocene
Oligocene transition.
AB - The glaciation of Antarctica at the Eocene-Oligocene transition (approx. 34
million years ago) was a major shift in the Earth's climate system, but the
mechanisms that caused the glaciation, and its effects, remain highly debated. A
number of recent studies have used coupled atmosphere-ocean climate models to
assess the climatic effects of Antarctic glacial inception, with often
contrasting results. Here, using the HadCM3L model, we show that the global
atmosphere and ocean response to growth of the Antarctic ice sheet is sensitive
to subtle variations in palaeogeography, using two reconstructions representing
Eocene and Oligocene geological stages. The earlier stage (Eocene; Priabonian),
which has a relatively constricted Tasman Seaway, shows a major increase in sea
surface temperature over the Pacific sector of the Southern Ocean in response to
the ice sheet. This response does not occur for the later stage (Oligocene;
Rupelian), which has a more open Tasman Seaway. This difference in temperature
response is attributed to reorganization of ocean currents between the stages.
Following ice sheet expansion in the earlier stage, the large Ross Sea gyre
circulation decreases in size. Stronger zonal flow through the Tasman Seaway
allows salinities to increase in the Ross Sea, deep-water formation initiates and
multiple feedbacks then occur amplifying the temperature response. This is
potentially a model-dependent result, but it highlights the sensitive nature of
model simulations to subtle variations in palaeogeography, and highlights the
need for coupled ice sheet-climate simulations to properly represent and
investigate feedback processes acting on these time scales.
PMID- 26438286
TI - The $10 trillion value of better information about the transient climate
response.
AB - How much is better information about climate change worth? Here, I use PAGE09, a
probabilistic integrated assessment model, to find the optimal paths of CO(2)
emissions over time and to calculate the value of better information about one
aspect of climate change, the transient climate response (TCR). Approximately
halving the uncertainty range for TCR has a net present value of about $10.3
trillion (year 2005 US$) if accomplished in time for emissions to be adjusted in
2020, falling to $9.7 trillion if accomplished by 2030. Probabilistic integrated
assessment modelling is the only method we have for making estimates like these
for the value of better information about the science and impacts of climate
change.
PMID- 26438287
TI - Feedbacks, climate sensitivity and the limits of linear models.
AB - The term 'feedback' is used ubiquitously in climate research, but implies varied
meanings in different contexts. From a specific process that locally affects a
quantity, to a formal framework that attempts to determine a global response to a
forcing, researchers use this term to separate, simplify and quantify parts of
the complex Earth system. We combine new model results with a historical and
educational perspective to organize existing ideas around feedbacks and linear
models. Our results suggest that the state- and forcing-dependency of feedbacks
are probably not appreciated enough, and not considered appropriately in many
studies. A non-constant feedback parameter likely explains some of the
differences in estimates of equilibrium climate sensitivity from different
methods and types of data. Clarifying the value and applicability of the linear
forcing feedback framework and a better quantification of feedbacks on various
timescales and spatial scales remains a high priority in order to better
understand past and predict future changes in the climate system.
PMID- 26438288
TI - Implementation and Outcomes of Forensic Housing First Programs.
AB - This mixed-method study used administrative data from 68 supportive housing
programs and evaluative and qualitative site visit data from a subset of four
forensic programs to (a) compare fidelity to the Housing First model and
residential client outcomes between forensic and nonforensic programs and (b)
investigate whether and how providers working in forensic programs can navigate
competing Housing First principles and criminal justice mandates. Quantitative
findings suggested that forensic programs were less likely to follow a harm
reduction approach to substance use and clients in those programs were more
likely to live in congregate settings. Qualitative findings suggested that an
interplay of court involvement, limited resources, and risk environments
influenced staff decisions regarding housing and treatment. Existing mental
health and criminal justice collaborations necessitate adaptation to the Housing
First model to accommodate client needs.
PMID- 26438289
TI - Estimation of Additive, Dominance, and Imprinting Genetic Variance Using Genomic
Data.
AB - Traditionally, exploration of genetic variance in humans, plants, and livestock
species has been limited mostly to the use of additive effects estimated using
pedigree data. However, with the development of dense panels of single-nucleotide
polymorphisms (SNPs), the exploration of genetic variation of complex traits is
moving from quantifying the resemblance between family members to the dissection
of genetic variation at individual loci. With SNPs, we were able to quantify the
contribution of additive, dominance, and imprinting variance to the total genetic
variance by using a SNP regression method. The method was validated in simulated
data and applied to three traits (number of teats, backfat, and lifetime daily
gain) in three purebred pig populations. In simulated data, the estimates of
additive, dominance, and imprinting variance were very close to the simulated
values. In real data, dominance effects account for a substantial proportion of
the total genetic variance (up to 44%) for these traits in these populations. The
contribution of imprinting to the total phenotypic variance of the evaluated
traits was relatively small (1-3%). Our results indicate a strong relationship
between additive variance explained per chromosome and chromosome length, which
has been described previously for other traits in other species. We also show
that a similar linear relationship exists for dominance and imprinting variance.
These novel results improve our understanding of the genetic architecture of the
evaluated traits and shows promise to apply the SNP regression method to other
traits and species, including human diseases.
PMID- 26438290
TI - Reassignment of Drosophila willistoni Genome Scaffolds to Chromosome II Arms.
AB - Drosophila willistoni is a geographically widespread Neotropical species. The
genome of strain Gd-H4-1 from Guadeloupe Island (Caribbean) was sequenced in 2007
as part of the 12 Drosophila Genomes Project. The assembled scaffolds were joined
based on conserved linkage and assigned to polytene chromosomes based on a
handful of genetic and physical markers. This paucity of markers was particularly
striking in the metacentric chromosome II, comprised two similarly sized arms,
IIL and IIR, traditionally considered homologous to Muller elements C and B,
respectively. In this paper we present the cytological mapping of 22 new gene
markers to increase the number of markers mapped by in situ hybridization and to
test the assignment of scaffolds to the polytene chromosome II arms. For this
purpose, we generated, by polymerase chain reaction amplification, one or two
gene probes from each scaffold assigned to the chromosome II arms and mapped
these probes to the Gd-H4-1 strain's polytene chromosomes by nonfluorescent in
situ hybridization. Our findings show that chromosome arms IIL and IIR correspond
to Muller elements B and C, respectively, directly contrasting the current
homology assignments in D. willistoni and constituting a major reassignment of
the scaffolds to chromosome II arms.
PMID- 26438291
TI - Joint Transcriptomic and Metabolomic Analyses Reveal Changes in the Primary
Metabolism and Imbalances in the Subgenome Orchestration in the Bread Wheat
Molecular Response to Fusarium graminearum.
AB - Fusarium head blight is a prevalent disease of bread wheat (Triticum aestivum
L.), which leads to considerable losses in yield and quality. Quantitative
resistance to the causative fungus Fusarium graminearum is poorly understood. We
integrated transcriptomics and metabolomics data to dissect the molecular
response to the fungus and its main virulence factor, the toxin deoxynivalenol in
near-isogenic lines segregating for two resistance quantitative trait loci, Fhb1
and Qfhs.ifa-5A. The data sets portrait rearrangements in the primary metabolism
and the translational machinery to counter the fungus and the effects of the
toxin and highlight distinct changes in the metabolism of glutamate in lines
carrying Qfhs.ifa-5A. These observations are possibly due to the activity of two
amino acid permeases located in the quantitative trait locus confidence interval,
which may contribute to increased pathogen endurance. Mapping to the highly
resolved region of Fhb1 reduced the list of candidates to few genes that are
specifically expressed in presence of the quantitative trait loci and in response
to the pathogen, which include a receptor-like protein kinase, a protein kinase,
and an E3 ubiquitin-protein ligase. On a genome-scale level, the individual
subgenomes of hexaploid wheat contribute differentially to defense. In
particular, the D subgenome exhibited a pronounced response to the pathogen and
contributed significantly to the overall defense response.
PMID- 26438292
TI - The Role of Mms22p in DNA Damage Response in Candida albicans.
AB - To ensure correct DNA replication, eukaryotes have signaling pathways that
respond to replication-associated DNA damage and trigger repair. In both
Saccharomyces cerevisiae and Schizosaccharomyces pombe, a complex of proteins,
including the cullin protein Rtt101p and two adapter proteins Mms22p and Mms1p,
is important for proper response to replication stress. We have investigated this
system in Candida albicans. In this pathogen, Mms22p is important for recovery
from DNA replication damage induced by agents including methylmethane sulfonate,
camptothecin, and ionizing radiation. Although no clear ortholog of Mms1p has
been identified in C. albicans, loss of either Mms22p or Rtt101p generates
similar damage sensitivity, consistent with a common function. In S. cerevisiae,
the Mrc1p-Csm3p-Tof1p complex stabilizes stalled replication forks and activates
a replication checkpoint and interacts with Mms22p. A similar complex in S.
pombe, consisting of the Tof1p and Csm3p orthologs Swi1p and Swi3p, along with
the fission yeast Mrc1p, genetically also interacts with Mms22p. Intriguingly in
C. albicans only Mrc1p and Csm3p appear involved in damage repair, and Mms22p is
required for responding to DNA damage agents in MRC1 or CSM3 conditional mutants.
In C. albicans, although the loss of RAD57 greatly impairs response in the
pathogen to many DNA-damaging agents, lethality due to camptothecin damage
requires concomitant loss of Rad57p and Mms22p, suggesting that Mms22p is only
essential for homologous recombination induced by camptothecin. These results
establish that although C. albicans uses conserved cellular modules to respond to
DNA damage and replication blocks, the specific details of these modules differ
significantly from the S. cerevisiae model.
PMID- 26438294
TI - Drosophila melanogaster Natural Variation Affects Growth Dynamics of Infecting
Listeria monocytogenes.
AB - We find that in a Listeria monocytogenes/Drosophila melanogaster infection model,
L. monocytogenes grows according to logistic kinetics, which means we can measure
both a maximal growth rate and growth plateau for the microbe. Genetic variation
of the host affects both of the pathogen growth parameters, and they can vary
independently. Because growth rates and ceilings both correlate with host
survival, both properties could drive evolution of the host. We find that growth
rates and ceilings are sensitive to the initial infectious dose in a host
genotype-dependent manner, implying that experimental results differ as we change
the original challenge dose within a single strain of host.
PMID- 26438293
TI - Markerless Escherichia coli rrn Deletion Strains for Genetic Determination of
Ribosomal Binding Sites.
AB - Single-copy rrn strains facilitate genetic ribosomal studies in Escherichia coli.
Consecutive markerless deletion of rrn operons resulted in slower growth upon
inactivation of the fourth copy, which was reversed by supplying transfer RNA
genes encoded in rrn operons in trans. Removal of the sixth, penultimate rrn copy
led to a reduced growth rate due to limited rrn gene dosage. Whole-genome
sequencing of variants of single-copy rrn strains revealed duplications of large
stretches of genomic DNA. The combination of selective pressure, resulting from
the decreased growth rate, and the six identical remaining scar sequences,
facilitating homologous recombination events, presumably leads to elevated
genomic instability.
PMID- 26438295
TI - Estimating Trait Heritability in Highly Fecund Species.
AB - Increasingly, researchers are interested in estimating the heritability of traits
for nonmodel organisms. However, estimating the heritability of these traits
presents both experimental and statistical challenges, which typically arise from
logistical difficulties associated with rearing large numbers of families
independently in the field, a lack of known pedigree, the need to account for
group or batch effects, etc. Here we develop both an empirical and computational
methodology for estimating the narrow-sense heritability of traits for highly
fecund species. Our experimental approach controls for undesirable culturing
effects while minimizing culture numbers, increasing feasibility in the field.
Our statistical approach accounts for known issues with model-selection by using
a permutation test to calculate significance values and includes both fitting and
power calculation methods. We further demonstrate that even with moderately high
sample-sizes, the p-values derived from asymptotic properties of the likelihood
ratio test are overly conservative, thus reducing statistical power. We
illustrate our methodology by estimating the narrow-sense heritability for larval
settlement, a key life-history trait, in the reef-building coral Orbicella
faveolata. The experimental, statistical, and computational methods, along with
all of the data from this study, are available in the R package multiDimBio.
PMID- 26438297
TI - A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy.
AB - A novel canine muscular dystrophy in Landseer dogs was observed. We had access to
five affected dogs from two litters. The clinical signs started at a few weeks of
age, and the severe progressive muscle weakness led to euthanasia between 5 and
15 months of age. The pedigrees of the affected dogs suggested a monogenic
autosomal-recessive inheritance of the trait. Linkage and homozygosity mapping
indicated two potential genome segments for the causative variant on chromosomes
10 and 31 harboring a total of 4.8 Mb of DNA or 0.2% of the canine genome. Using
the Illumina sequencing technology, we obtained a whole-genome sequence from one
affected Landseer. Variants were called with respect to the dog reference genome
and compared with the genetic variants of 170 control dogs from other breeds. The
affected Landseer dog was homozygous for a single, private nonsynonymous variant
in the critical intervals, a nonsense variant in the COL6A1 gene
(Chr31:39,303,964G>T; COL6A1:c.289G>T; p.E97*). Genotypes at this variant showed
perfect concordance with the muscular dystrophy phenotype in all five cases and
more than 1000 control dogs. Variants in the human COL6A1 gene cause Bethlem
myopathy or Ullrich congenital muscular dystrophy. We therefore conclude that the
identified canine COL6A1 variant is most likely causative for the observed
muscular dystrophy in Landseer dogs. On the basis of the nature of the genetic
variant in Landseer dogs and their severe clinical phenotype these dogs represent
a model for human Ullrich congenital muscular dystrophy.
PMID- 26438296
TI - Sleeping Beauty Transposon Mutagenesis as a Tool for Gene Discovery in the NOD
Mouse Model of Type 1 Diabetes.
AB - A number of different strategies have been used to identify genes for which
genetic variation contributes to type 1 diabetes (T1D) pathogenesis. Genetic
studies in humans have identified >40 loci that affect the risk for developing
T1D, but the underlying causative alleles are often difficult to pinpoint or have
subtle biological effects. A complementary strategy to identifying "natural"
alleles in the human population is to engineer "artificial" alleles within inbred
mouse strains and determine their effect on T1D incidence. We describe the use of
the Sleeping Beauty (SB) transposon mutagenesis system in the nonobese diabetic
(NOD) mouse strain, which harbors a genetic background predisposed to developing
T1D. Mutagenesis in this system is random, but a green fluorescent protein (GFP)
polyA gene trap within the SB transposon enables early detection of mice
harboring transposon-disrupted genes. The SB transposon also acts as a molecular
tag to, without additional breeding, efficiently identify mutated genes and
prioritize mutant mice for further characterization. We show here that the SB
transposon is functional in NOD mice and can produce a null allele in a novel
candidate gene that increases diabetes incidence. We propose that SB transposon
mutagenesis could be used as a complementary strategy to traditional methods to
help identify genes that, when disrupted, affect T1D pathogenesis.
PMID- 26438298
TI - Tc1-like Transposase Thm3 of Silver Carp (Hypophthalmichthys molitrix) Can
Mediate Gene Transposition in the Genome of Blunt Snout Bream (Megalobrama
amblycephala).
AB - Tc1-like transposons consist of an inverted repeat sequence flanking a
transposase gene that exhibits similarity to the mobile DNA element, Tc1, of the
nematode, Caenorhabditis elegans. They are widely distributed within vertebrate
genomes including teleost fish; however, few active Tc1-like transposases have
been discovered. In this study, 17 Tc1-like transposon sequences were isolated
from 10 freshwater fish species belonging to the families Cyprinidae,
Adrianichthyidae, Cichlidae, and Salmonidae. We conducted phylogenetic analyses
of these sequences using previously isolated Tc1-like transposases and report
that 16 of these elements comprise a new subfamily of Tc1-like transposons. In
particular, we show that one transposon, Thm3 from silver carp
(Hypophthalmichthys molitrix; Cyprinidae), can encode a 335-aa transposase with
apparently intact domains, containing three to five copies in its genome. We then
coinjected donor plasmids harboring 367 bp of the left end and 230 bp of the
right end of the nonautonomous silver carp Thm1 cis-element along with capped
Thm3 transposase RNA into the embryos of blunt snout bream (Megalobrama
amblycephala; one- to two-cell embryos). This experiment revealed that the
average integration rate could reach 50.6% in adult fish. Within the blunt snout
bream genome, the TA dinucleotide direct repeat, which is the signature of Tc1
like family of transposons, was created adjacent to both ends of Thm1 at the
integration sites. Our results indicate that the silver carp Thm3 transposase can
mediate gene insertion by transposition within the genome of blunt snout bream
genome, and that this occurs with a TA position preference.
PMID- 26438300
TI - Unlike in clear cell renal cell carcinoma, KRAS is not mutated in multilocular
cystic clear cell renal cell neoplasm of low potential.
AB - The recent International Society Urological Pathology (ISUP) Vancouver
classification of renal neoplasia distinguishes between clear cell renal cell
carcinoma (CCRCC) and multilocular cystic clear cell renal cell neoplasm of low
malignant potential (mcCCRCNLMP). Current data supports the latter being a low
aggressive neoplasm which does not recur or metastasize after definitive surgical
treatment. Therefore, differentiating mcCCRCNLMP from low-grade CCRCC with cystic
changes is important for patient management. The role of the pathologist is
crucial in distinguishing between both entities. Since these tumors have
overlapping molecular features, including 3p deletion and VHL mutations, it would
be potentially clinically relevant to identify other molecular differences which
might help to differentiate between these entities. We studied six different
codons of KRAS and six codons of NRAS in mcCCRCNLMP and CCRCC of low grade and
stage. All cases of CCRCC had a mutation in one of the studied KRAS codons. In
contrast, no mutations were found in mcCCRCNLMP. We provide preliminary data to
support that CCRCC and mcCCRCNLMP, in spite of their histologic similarity, show
a different pattern of KRAS gene mutation, which is consistent with the observed
differences in disease progression between these tumors.
PMID- 26438299
TI - HES-Mediated Repression of Pten in Caenorhabditis elegans.
AB - The hairy/enhancer-of-split (HES) group of transcription factors controls
embryonic development, often by acting downstream of the Notch signaling pathway;
however, little is known about postembryonic roles of these proteins. In
Caenorhabditis elegans, the six proteins that make up the REF-1 family are
considered to be HES orthologs that act in both Notch-dependent and Notch
independent pathways to regulate embryonic events. To further our understanding
of how the REF-1 family works to coordinate postembryonic cellular events, we
performed a functional characterization of the REF-1 family member, HLH-25. We
show that, after embryogenesis, hlh-25 expression persists throughout every
developmental stage, including dauer, into adulthood. Like animals that carry
loss-of-function alleles in genes required for normal cell-cycle progression, the
phenotypes of hlh-25 animals include reduced brood size, unfertilized oocytes,
and abnormal gonad morphology. Using gene expression microarray, we show that the
HLH-25 transcriptional network correlates with the phenotypes of hlh-25 animals
and that the C. elegans Pten ortholog, daf-18, is one major hub in the network.
Finally, we show that HLH-25 regulates C. elegans lifespan and dauer recovery,
which correlates with a role in the transcriptional repression of daf-18
activity. Collectively, these data provide the first genetic evidence that HLH-25
may be a functional ortholog of mammalian HES1, which represses PTEN activity in
mice and human cells.
PMID- 26438301
TI - Deconvolution of the vestibular evoked myogenic potential using the power
spectrum of the electromyogram.
AB - BACKGROUND: The vestibular evoked myogenic potential (VEMP) can be modelled
reasonably well by convolving two functions: one representing an average motor
unit action potential (MUAP), the other representing the temporal modulation of
the MUAP rate (rate modulation). It is the latter which contains the information
of interest, and so it would be desirable to be able to estimate this function
from a combination of the VEMP with some other data. As the VEMP is simply a
stimulus-triggered average of the electromyogram (EMG), a supplementary, easily
accessible source of information is the EMG power spectrum, which can be shown to
be roughly proportional to the squared modulus of the Fourier transform of the
MUAP. But no phase information is available for the MUAP so that a
straightforward deconvolution is not possible. METHODS: To get around the problem
of incomplete information, the rate modulation is described by a thoughtfully
chosen function with just a few adjustable parameters. The convolution model is
then used to make predictions as to the energy spectral density of the VEMP, and
the parameters are optimized using a cost function that quantifies the difference
between model prediction and data. RESULTS: The workability of the proposed
approach is demonstrated by analysing Monte Carlo simulated data and exemplary
data from patients who underwent VEMP testing as part of a clinical evaluation of
their dizziness symptoms. CONCLUSIONS: The approach is suited, for example, to
estimate the duration of the inhibition causing the VEMP or to disentangle a VEMP
consisting of more than one component.
PMID- 26438302
TI - Sharing data from MS clinical trials: Opportunities, challenges, and future
directions.
AB - The treatment of people affected by multiple sclerosis, particularly the
relapsing forms of the disease, has been transformed by the availability of
various therapeutic agents. This landmark progress is due to an enormous
foundation of clinical research and, particularly, numerous phase II and III
clinical trials. Although the research community has many reasons to take pride
in this progress, a fundamental question remains about whether opportunities for
additional research are being lost due to inadequate clinical trial data sharing.
PMID- 26438303
TI - Multiple sclerosis relapse phenotype is an important, neglected, determinant of
disease outcome - YES.
PMID- 26438304
TI - Multiple sclerosis relapse phenotype is an important, neglected, determinant of
disease outcome - NO.
PMID- 26438305
TI - Multiple sclerosis relapse phenotype is an important, neglected determinant of
disease-outcome: Commentary.
PMID- 26438306
TI - The burden of multiple sclerosis variants in continental Italians and Sardinians.
AB - BACKGROUND: Recent studies identified > 100 non-HLA (human leukocyte antigen)
multiple sclerosis (MS) susceptibility variants in Northern European populations,
but their role in Southern Europeans is largely unexplored. OBJECTIVE: We aimed
to investigate the cumulative impact of those variants in two Mediterranean
populations: Continental Italians and Sardinians. METHODS: We calculated four
weighted Genetic Risk Scores (wGRS), using up to 102 non-HLA MS risk variants and
5 HLA MS susceptibility markers in 1691 patients and 2194 controls from
continental Italy; and 2861 patients and 3034 controls from Sardinia. We then
assessed the differences between populations using Nagelkerke's R(2) and the area
under the Receiver Operating Characteristic (ROC) curves. RESULTS: As expected,
the genetic burden (mean wGRS value) was significantly higher in MS patients than
in controls, in both populations. Of note, the burden was significantly higher in
Sardinians. Conversely, the proportion of variability explained and the
predictive power were significantly higher in continental Italians. Notably,
within the Sardinian patients, we also observed a significantly higher burden of
non-HLA variants in individuals who do not carry HLA risk alleles. CONCLUSIONS:
The observed differences in MS genetic burden between the two Mediterranean
populations highlight the need for more genetic studies in South Europeans, to
further expand the knowledge of MS genetics.
PMID- 26438307
TI - Treatment of osteoporosis after alendronate or risedronate.
AB - Alendronate (ALN) and risedronate (RIS) are ideal as first-choice therapy options
in the treatment of postmenopausal osteoporosis. What to do for patients who do
not respond adequately to bisphosphonates has not been conclusively determined,
but transitioning to other therapies should be considered. The aim of this
article is to describe potential alternatives for patients switching from ALN or
RIS to other therapies for osteoporosis. A systematic search of PubMed was
conducted to find papers that evaluate the effects of switching therapies on
fractures, bone mineral density (BMD), or bone turnover markers. Results from 11
studies that prospectively assessed treatment after ALN or RIS in women with
postmenopausal osteoporosis were reviewed. All studies are of short duration (all
24 months or less) and assess the topic of transitioning therapy from ALN or RIS.
None of the studies had the statistical power to assess fracture-reduction
efficacy. Transitioning from ALN to zoledronic acid maintains therapeutic effects
for 12 months. Switching to strontium ranelate, denosumab, or teriparatide causes
further increases in BMD. Specifically, transitioning to teriparatide could be
used for a limited time for select patients but needs to be followed up with anti
resorptive treatment to prevent a loss of the bone gained. There are only few
studies-of short duration-that assess the topic of transitioning therapy from ALN
or RIS, although this is a very frequent occurrence in clinical practice. This is
especially true if the patient has not reached his/her therapy goal. Further long
term studies are needed.
PMID- 26438308
TI - Does salmon calcitonin cause cancer? A review and meta-analysis.
AB - Recently an association between the use of calcitonin and cancer has been
postulated. We reviewed the biological rationale and performed an additional
analysis of historical data with respect to the possibility. An association
cannot be excluded, but the relationship is weak and causality is unlikely. The
purpose of the present study is to review the strength of association and
likelihood of a causal relationship between use of calcitonin and cancer. We
reviewed the evidence for this association, including the molecular signaling
mechanisms of calcitonin, preclinical data, an "experiment of nature," and the
results of a previous meta-analysis which showed a weak association. We performed
an additional meta-analysis to incorporate the data from a novel investigational
oral formulation of salmon calcitonin. Review of the literature did not identify
a cellular signaling mechanism of action which might account for a causal
relationship or toxicologic or postmarketing data to support the thesis.
Additional clinical results incorporated into previous meta-analyses weakened but
did not completely negate the possibility of association. A causal association
between calcitonin use and malignancy is unlikely, as there is little biological
plausibility. The preponderance of nonclinical and clinical evidence also does
not favor a causal relationship.
PMID- 26438309
TI - Non-hip and non-vertebral fractures: the neglected fracture sites.
AB - SUMMARY: Non-hip, non-vertebral fractures (NHNVF) were compared with hip,
vertebral and controls. NHNVF were younger and heavier than controls and
hip/vertebral fractures in both men and women, respectively. Falls and prior
fractures were less common in NHNVF than hip fractures. Glucocorticoid use was
lower in NHNVF compared to vertebral fracture (VF) in men. INTRODUCTION: Although
hip fracture (HF) and vertebral fractures (VF) receive the most attention in the
literature and are the targeted sites for fracture prevention, non-hip, non
vertebral fracture (NHNVF) sites account for a greater proportion of fractures
than the hip or vertebrae. This study aimed to assess risk factors for NHNVF and
compare them with those for HF, VF and controls. METHODS: Incident fractures
during 2005-2007 for men and 1994-1996 for women were identified using
computerised keyword searches of radiological reports, and controls were selected
at random from electoral rolls for participation in the Geelong Osteoporosis
Study. Participants aged 60+ years were included in this study. RESULTS: Compared
to controls, men and women with NHNVF were younger (ORs, 0.90, 95% CI 0.86-0.94;
and 0.96, 0.93-0.98, respectively) and had a lower femoral neck bone mineral
density (BMD) T-score (age-adjusted; difference [men] 0.383, P = 0.002; [women]
0.287, P = 0.001). Compared to HF, men and women with NHNVF were heavier
(difference [men] 9.0 kg, P = 0.01; [women] 7.6 kg, P < 0.001). Heavier weight
was also a risk factor for women with NHNVF compared to VF (1.03, 1.01-1.06). In
men with NHNVF, falls (0.37, 0.14-0.97) and prior fractures (0.38, 0.15-0.98)
were less common compared to HF; and glucocorticoid use was less common for NHNVF
(0.30, 0.11-0.85) compared to VF. CONCLUSIONS: Given the high numbers of NHNVF
sustained by men and women in this study, fracture prevention strategies should
focus on individuals with high risk of sustaining these types of fractures, as
well as on individuals who are more likely to sustain a HF or VF.
PMID- 26438310
TI - The effects of visceral obesity and androgens on bone: trenbolone protects
against loss of femoral bone mineral density and structural strength in
viscerally obese and testosterone-deficient male rats.
AB - SUMMARY: In males, visceral obesity and androgen deficiency often present
together and result in harmful effects on bone. Our findings show that both
factors are independently associated with adverse effects on femoral bone
structure and strength, and trenbolone protects rats from diet-induced visceral
obesity and consequently normalises femoral bone structural strength.
INTRODUCTION: In light of the rapidly increasing incidence of obesity and
osteoporosis globally, and recent conjecture regarding the effects of visceral
adiposity and testosterone deficiency on bone health, we investigated the effects
of increased visceral adipose tissue (VAT) mass on femoral bone mineral density
(BMD), structure and strength in normal weight rats with testosterone deficiency.
METHODS: Male Wistar rats (n = 50) were fed either standard rat chow (CTRL, n =
10) or a high-fat/high-sugar diet (HF/HS, n = 40). Following 8 weeks of feeding,
rats underwent sham surgery (CTRL, n = 10; HF/HS, n = 10) or orchiectomy (HF/HS +
ORX, n = 30). Following a 4-week recovery period, mini-osmotic pumps containing
either vehicle (CTRL, n = 10; HF/HS, n = 10; HF/HS + ORX, n = 10), 2.0 mg kg day(
1), testosterone (HF/HS + ORX + TEST, n = 10) or 2.0 mg kg day(-1) trenbolone
(HF/HS + ORX + TREN, n = 10) were implanted for 8 weeks of treatment. Dual-energy
X-ray absorptiometry and three-point bending tests were used to assess bone mass,
structure and strength of femora. RESULTS: Diet-induced visceral obesity resulted
in decreased bone mineral area (BMA) and content (BMC) and impaired femoral
stiffness and strength. Orchiectomy further impaired BMA, BMC and BMD and reduced
energy to failure in viscerally obese animals. Both TEST and TREN treatment
restored BMA, BMC, BMD and energy to failure. Only TREN reduced visceral
adiposity and improved femoral stiffness and strength. CONCLUSIONS: Findings
support a role for both visceral adiposity and testosterone deficiency as
independent risk factors for femoral osteoporosis, adverse bone geometry and
impaired bone strength in male rats. Trenbolone may be a more effective candidate
for androgen replacement therapy than testosterone in viscerally obese
testosterone-deficient males.
PMID- 26438311
TI - Development of a generic Ehrlichia FRET-qPCR and investigation of ehrlichioses in
domestic ruminants on five Caribbean islands.
AB - BACKGROUND: The Ehrlichia are obligate intracellular Gram-negative tick-borne
bacteria that are important human and animal pathogens. There is a need for
assays to rapidly and reliably detect and differentiate the five generally
recognized species into groups in a single reaction: E. canis, E. chaffeensis, E.
ewingii, E. muris and E. ruminantium. METHODS: We developed primers and probes
against the 16S rRNA gene to enable us to reliably detect the five major
Ehrlichia spp. in a single FRET-qPCR. We tested the Ehrlichia FRET-qPCR on
reference strains and on DNA from the blood of domestic ruminants from five
Caribbean islands. The Ehrlichia present were determined using melting point
analysis and by sequencing the Ehrlichia FRET-qPCR products as well as those of a
nested PCR against the citrate synthase gene (gltA). RESULTS: Our Ehrlichia FRET
qPCR was negative for the closely related Anaplasma marginale and A.
phagocytophilum but gave positive reactions with reference strains of the most
generally recognized species and with other less characterized Ehrlichia of
domestic ruminants, mainly E. ovina, the Panola Mountain Ehrlichia, and Ehrlichia
sp. BOV2010. Melting point analysis revealed 4 distinct groups: E. ruminantium (T
m ~55.8 degrees C); E. chaffeensis and E. ewingii (T m ~57.7 degrees C); E.
canis, E. muris, E. ovina and Ehrlichia sp. BOV 2010 (T m ~62.0 degrees C); and
the Panola Mountain Ehrlichia (T m ~65.5 degrees C). The detection limit of the
FRET-qPCR was ~ 5 gene copies in a reaction and the sequences of the FRET-qPCR
products were as expected. With DNA from domestic ruminants from the Caribbean we
found 12.2 % (134/1,101) positive: cattle (76/385; 19.7 %), sheep (45/340; 13.2
%) and goats (13/376; 3.5 %). Melting point analysis and sequencing of the FRET
qPCR and nested PCR gltA products showed the Ehrlichia we detected were E. canis
or very closely related organisms. CONCLUSIONS: In a single reaction, our
Ehrlichia FRET-qPCR can detect the Ehrlichia spp. we studied and differentiate
them into four groups. Domestic ruminants in the Caribbean are not uncommonly
exposed to Ehrlichia, possibly E. canis or very closely related organisms.
PMID- 26438313
TI - Exploration of Peptide Inhibitors of Human Squalene Synthase through Molecular
Modeling and Phage Display Technique.
AB - Many studies have demonstrated the role of elevated levels of serum cholesterol
in the pathogenesis of atherosclerosis and coronary heart disease. Various drugs
targeting the key enzymes involved in the cholesterol biosynthesis pathway have
been investigated for the treatment of hypercholesterolemia. Human squalene
synthase has been one of the most important targets for therapeutic intervention.
In the present study, we used the recombinant human squalene synthase as the lure
for screening the peptide inhibitors from phage-displayed random peptide library.
The tightly bound phages and their derived peptides were further evaluated based
on their potential binding capabilities, molecular modeling characteristics and
predicted absorption, distribution, metabolism, excretion, toxicity (ADMET)
properties. Several hexa-peptides and tetra-peptides were finally synthesized to
assay their inhibitory effects toward the recombinant human squalene synthase.
The results demonstrated that the hexa-peptide FTACNW and tetra-peptide VACL can
inhibit human squalene synthase effectively (with IC50 values near 100 MUM) and
may have potential to develop further as future hypocholesterolemia agents.
PMID- 26438314
TI - Efficient Cadmium Bioaccumulation by Displayed Hybrid CS3 Pili: Effect of Heavy
Metal Binding Motif Insertion Site on Adsorption Capacity and Selectivity.
AB - The objective of this study was to evaluate the influence of insertion site of
the metal binding motif on the bioaccumulation capacity of the hybrid CS3 pili
displayed on the surface of Escherichia coli using both computational and
experimental methods. Two metal binding motifs (cadmium binding motif (cbm) and
cadmium binding beta motif (cbbetam)), identified by searching against the
PROSITE database, were inserted into five putative permissive sites of CstH
protein (CS3 pili subunit) by using SOEing PCR technique. The expression and
surface display of the hybrid pili were evaluated using dot and Western blotting
methods and also immunofluorescence microscopy. The cadmium binding affinity and
selectivity of the recombinant bacteria displaying various hybrid pili were
evaluated using atomic absorption procedure. The results showed that the cadmium
binding motifs enabled the cells to sequester cadmium 8- to 16-fold higher than
the E.coli expressing native pili. The location of the metal binding motifs in
the pili subunit had also a significant effect on the metal-binding properties of
the hybrid pili. The insertion at positions 107-108 and 92-93 of the mature CstH
showed the highest adsorption in comparison to other positions.
PMID- 26438312
TI - Genome analyses of the sunflower pathogen Plasmopara halstedii provide insights
into effector evolution in downy mildews and Phytophthora.
AB - BACKGROUND: Downy mildews are the most speciose group of oomycetes and affect
crops of great economic importance. So far, there is only a single deeply
sequenced downy mildew genome available, from Hyaloperonospora arabidopsidis.
Further genomic resources for downy mildews are required to study their
evolution, including pathogenicity effector proteins, such as RxLR effectors.
Plasmopara halstedii is a devastating pathogen of sunflower and a potential
pathosystem model to study downy mildews, as several Avr-genes and R-genes have
been predicted and unlike Arabidopsis downy mildew, large quantities of almost
contamination-free material can be obtained easily. RESULTS: Here a high-quality
draft genome of Plasmopara halstedii is reported and analysed with respect to
various aspects, including genome organisation, secondary metabolism, effector
proteins and comparative genomics with other sequenced oomycetes. Interestingly,
the present analyses revealed further variation of the RxLR motif, suggesting an
important role of the conservation of the dEER-motif. Orthology analyses revealed
the conservation of 28 RxLR-like core effectors among Phytophthora species. Only
six putative RxLR-like effectors were shared by the two sequenced downy mildews,
highlighting the fast and largely independent evolution of two of the three major
downy mildew lineages. This is seemingly supported by phylogenomic results, in
which downy mildews did not appear to be monophyletic. CONCLUSIONS: The genome
resource will be useful for developing markers for monitoring the pathogen
population and might provide the basis for new approaches to fight Phytophthora
and downy mildew pathogens by targeting core pathogenicity effectors.
PMID- 26438315
TI - Cloning, Expression, and Purification of Xylanase Gene from Bacillus
licheniformis for Use in Saccharification of Plant Biomass.
AB - The xylanase gene (xynA) of Bacillus licheniformis 9945A was cloned and expressed
in Escherichia coli BL21(DE3) using pET-22b(+) as an expression vector. The
recombinant xylanase enzyme was purified by ammonium sulfate precipitation,
followed by single-step immobilized metal ion affinity chromatography with a
57.58-fold purification having 138.2 U/mg specific activity and recovery of 70.08
%. Molecular weight of the purified xylanase, 23 kDa, was determined by sodium
dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme was
stable for up to 70 degrees C with a broad pH range of 4-9 pH units. The enzyme
activity was increased in the presence of metal ions especially Ca(+2) and
decreased in the presence of EDTA, indicating that the xylanase was a
metalloenzyme. However, an addition of 1-4 % Tween 80, beta-mercaptoethanol, and
DTT resulted in the increase of enzyme activity by 51, 52, and 5 %, respectively.
Organic solvents with a concentration of 10-40 % slightly decreased the enzyme
activity. The xylanase enzyme possesses the ability of bioconversion of plant
biomasses like wheat straw, rice straw, and sugarcane bagasse. Among the
different tested biomasses, the highest saccharification percentage was observed
with 1 % sugarcane bagasse after 72 h of incubation at 50 degrees C with 20
units of enzyme. The results suggest that recombinant xylanase can be used in the
bioconversion of natural biomasses into simple sugars which could be further used
for the production of biofuel.
PMID- 26438316
TI - GLP-1 Receptor Agonists and Type 1 Diabetes - Where Do We Stand?
AB - Type 1 diabetes (T1DM) is a disease characterized by autoimmune mediated
destruction of the insulin producing beta cells of endocrine pancreas. Beside
insulin deficiency, T1DM is also characterized by abnormal suppression of
glucagon secretion in response to hyperglycemia. All these abnormalities are
likely to leave patients dependent upon exogenous insulin administration for
survival. GLP-1 is a hormone secreted by L-cells of distal small intestine and
colon. GLP-1 exerts its effects through the interaction with GLP-1 receptor
expressed in the pancreatic islets, lung, hypothalamus, stomach, heart and
kidney. It belongs to the group of incretin peptides and it stimulates insulin
and inhibits glucagon secretion. Actions of GLP-1 also include delaying of
gastric emptying, reduction of appetite and induction of satiety. On the other
hand, evidences mainly collected from animal models, have indicated the role of
GLP-1 in increasing beta cell proliferation and differentiation and in decreasing
the rate of beta cell apoptosis. GLP-1 receptor agonists are approved for the
treatment of type 2 diabetes where they have established very important position.
However, they are still not approved for use in T1DM, although they could have
beneficial effects in both new onset and longstanding T1DM patients, mainly as an
adjunctive therapy to insulin in order to improve glycemic control and body
weight management in longstanding disease or to reduce insulin requirements or
even to delay the absolute dependence upon insulin administration in new onset
T1DM. Randomized, long-term, placebo controlled clinical trials are warranted
before the official implementation of GLP-1 receptor agonists in the treatment of
T1DM.
PMID- 26438317
TI - Integrating care for individuals with FASD: results from a multi-stakeholder
symposium.
AB - BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) has a significant impact on
communities and systems such as health, education, justice and social services.
FASD is a complex neurodevelopmental disorder that results in permanent
disabilities and associated service needs that change across affected
individuals' lifespans. There is a degree of interdependency among medical and
non-medical providers across these systems that do not frequently meet or plan a
coordinated continuum of care. Improving overall care integration will increase
provider-specific and system capacity, satisfaction, quality of life and
outcomes. METHODS: We conducted a consensus generating symposium comprised of 60
experts from different stakeholder groups: Allied & Mental Health, Education,
First Nations & Metis Health, Advocates, Primary Care, Government Health Policy,
Regional FASD Coordinators, Social Services, and Youth Justice. Research
questions addressed barriers and solutions to integration across systems and
group-specific and system-wide research priorities. Solutions and consensus on
prioritized lists were generated by combining the Electronic Meeting System
approach with a modified 'Nominal Group Technique'. RESULTS: FASD capacity (e.g.,
training, education, awareness) needs to be increased in both medical and non
medical providers. Outcomes and integration will be improved by implementing:
multidisciplinary primary care group practice models, FASD system
navigators/advocates, and patient centred medical homes. Electronic medical
records that are accessible to multiple medical and non-medical providers are a
key tool to enhancing integration and quality. Eligibility criteria for services
are a main barrier to integration across systems. There is a need for culturally
and community-specific approaches for First Nations communities. CONCLUSIONS:
There is a need to better integrate care for individuals and families living with
FASD. Primary Care is well positioned to play a central and important role in
facilitating and supporting increased integration. Research is needed to better
address best practices (e.g., interventions, supports and programs) and long-term
individual and family outcomes following a diagnosis of FASD.
PMID- 26438318
TI - Do Targeted Stipend Programs Reduce Gender and Socioeconomic Inequalities in
Schooling Attainment? Insights From Rural Bangladesh.
AB - Social investment in schooling in low-income countries has increased greatly in
the 1990s and 2000s because of the robust associations among schooling and
demographic, economic, and health outcomes. This analysis investigates whether
targeted school-attendance stipend programs succeeded in reducing gender and
socioeconomic inequalities in school attainment among a sample of the rural poor
in Bangladesh. Multivariate analyses find that targeted stipend programs helped
to reduce the gender attainment gap. Females had an increased probability of
participating in stipend programs, and returns to stipend participation were
significantly higher for females. However, stipend programs failed to reduce the
relative achievement gap between children of different socioeconomic backgrounds:
low socioeconomic status (SES) was associated with a decreased probability of
stipend participation, and stipend-related schooling gains for lower-SES females
were matched by comparable gains for higher-SES females. Meanwhile, there was no
significant association between stipend participation and schooling attainment
for males.
PMID- 26438319
TI - An Environmental Cause Common to Sex Determination and Infant Mortality.
PMID- 26438320
TI - The role of serum osteoprotegerin and receptor-activator of nuclear factor-kappaB
ligand in metabolic bone disease of women after obesity surgery.
AB - Metabolic bone disease may appear as a complication of obesity surgery. Because
an imbalance in the osteoprotegerin and receptor-activator of nuclear factor
kappaB ligand system may underlie osteoporosis, we aimed to study this system in
humans in the metabolic bone disease occurring after obesity surgery. In this
study we included sixty women with a mean age of 47 +/- 10 years studied 7 +/- 2
years after bariatric surgery. The variables studied were bone mineral density,
beta-isomer of C-terminal telopeptide of type I collagen cross-links (a bone
resorption marker), the bone formation markers osteocalcin and N-terminal
propeptide of procollagen 1, serum osteoprotegerin and receptor-activator of
nuclear factor-kappaB ligand. Serum osteoprotegerin inversely correlated with the
bone remodeling markers osteocalcin, beta-isomer of C-terminal telopeptide of
type I collagen cross-links and N-terminal propeptide of procollagen 1. The
osteoprotegerin and receptor-activator of nuclear factor-kappaB ligand ratio also
correlated inversely with serum parathormone and osteocalcin. Bone mineral
density at the lumbar spine was associated with age (beta = -0.235, P = 0.046),
percentage of weight loss (beta = 0.421, P = 0.001) and osteoprotegerin and
receptor-activator of nuclear factor-kappaB ligand ratio (beta = 0.259, P =
0.029) in stepwise multivariate analysis (R 2 = 0.29, F = 7.49, P < 0.001). Bone
mineral density at the hip site was associated only with percentage of weight
loss (beta = 0.464, P < 0.001) in stepwise multivariate regression (R 2 = 0.21, F
= 15.1, P < 0.001). These data show that the osteoprotegerin and receptor
activator of nuclear factor-kappaB ligand system is associated with bone markers
and bone mineral density at the lumbar spine after obesity surgery.
PMID- 26438322
TI - Identification of patients with suboptimal results after hip arthroplasty:
development of a preliminary prediction algorithm.
AB - BACKGROUND: The ability to predict preoperatively the identity of patients
undergoing hip arthroplasty at risk of suboptimal outcomes could help implement
interventions targeted at improving surgical results. The objective was to
develop a preliminary prediction algorithm (PA) allowing the identification of
patients at risk of unsatisfactory outcomes one to two years following hip
arthroplasty. METHODS: Retrospective data on a cohort of 265 patients having
undergone primary unilateral hip replacement (188 total arthroplasties and 77
resurfacing arthroplasties) from 2004 to 2010 were collected from our
arthroplasty database. Hip pain and function, as measured by the Western Ontario
and McMaster Universities Osteoarthritis Index (WOMAC) were collected, as well as
self-reported hip joint perception after surgery. Demographic and clinical
variables recorded at the time of the surgery were considered as potential
predictors. Patients were considered as having a suboptimal surgical outcome if
they were in the worst quartile of the postoperative total WOMAC score and
perceived their operated hip as artificial with minimal or major limitations. The
PA was developed using recursive partitioning. RESULTS: Mean postoperative
surgical follow-up was 446 +/- 171 days. Forty patients (15.1 %) had a
postoperative total WOMAC score in the worst quartile (>11.5/100) and perceived
their joint as artificial with minimal or major restrictions. A PA consisting of
the following variables achieved the most acceptable level of prediction: gender,
age at the time of surgery, body mass index (BMI), and three items of the
preoperative WOMAC (degree of pain with walking on a flat surface and during the
night as well as degree of difficulty with putting socks or stockings). The rule
had a sensitivity of 75.0 % (95 % CI: 59.8-85.8), a specificity of 77.8 % (95 %
CI: 71.9-82.7), a positive predictive value of 37.5 % (95 % CI: 27.7-48.5), a
negative predictive value of 94.6 % (95 % CI: 90.3-97.0) and positive and
negative likelihood ratios of 3.38 (95 % CI: 2.49-4.57) and 0.34 (95 % CI: 0.19
0.55) respectively. CONCLUSIONS: The preliminary PA shows promising results at
identifying patients at risk of significant functional limitations, increased
pain and inadequate joint perception after hip arthroplasty. Clinical use should
not be implemented before additional validation and refining.
PMID- 26438321
TI - Factors associated with growth disturbance at celiac disease diagnosis in
children: a retrospective cohort study.
AB - BACKGROUND: Impaired growth is a well-known complication in celiac disease, but
factors associated with it are poorly known. We investigated this issue in a
large cohort of children. METHODS: 530 children with biopsy-proven celiac disease
were included. The participants were divided into two groups on the basis of the
presence (n = 182) or absence (n = 348) of growth disturbance at diagnosis.
Histological, serological and clinical characteristics were compared between
children with growth failure and those with normal growth. Further, patients with
growth failure as the sole clinical presentation were compared to those with poor
growth and concomitant other symptoms. RESULTS: Children with growth failure were
younger (p < 0.001) and had lower hemoglobin (p = 0.016) and higher celiac
antibody (p < 0.001), alanine aminotransferase (p = 0.035) and thyroid
stimulating hormone values (p = 0.013) than those with normal growth.
Significantly associated with growth failure at diagnosis were age <3 years (OR
4.3 (95 % CI 2.5-7.5) vs older age), diagnosis before the year 2000 and in 2000
09 (OR 3.1 (1.8-5.4) and OR 1.8 (1.1-2.8) vs diagnosis in 2010-2013), presence of
total and subtotal villous atrophy (OR 4.2 (2.5-7.0) and OR 2.0 (1.3-3.2) vs
partial atrophy), severe symptoms (OR 3.4 (1.8-6.7) vs mild symptoms) and
vomiting (OR 3.1 (1.5-6.3). The presence of abdominal pain reduced the risk (OR
0.5 (0.3-0.7)), while there was no effect of gender, diarrhea, constipation,
other chronic diseases and celiac disease in the family. Children evincing poor
growth as the sole clinical presentation were older (p < 0.001) and had higher
hemoglobin (P < 0.001) and total iron (p = 0.010) values and lower TG2ab values
(p = 0.009) than those with growth disturbance and other symptoms. CONCLUSIONS:
In particular young age and severe clinical and histological presentation were
associated with growth disturbance at celiac disease diagnosis. Children with
only poor growth are markedly different from those with other concomitant
symptoms, suggesting different pathogenic mechanisms.
PMID- 26438323
TI - Australian GP management of osteoarthritis following the release of the RACGP
guideline for the non-surgical management of hip and knee osteoarthritis.
AB - BACKGROUND: Osteoarthritis (OA) is a highly disabling and costly condition with
an escalating prevalence in Australia due to the ageing and increasing obesity of
the population. The general practitioner (GP) plays a central role in the
management of this condition. The aim of this study was to examine opinions about
the management of OA by Australian GPs following the release of the Royal
Australian College of General Practitioners Guideline for the non-surgical
management of hip and knee OA (RACGP OA CPG), and to compare the results with an
earlier survey administered by the National Prescribing Service. METHODS: In
January 2013, a self-administered questionnaire was sent to 228 GPs to determine
their treatment approaches to OA management using a clinical vignette of a
patient with OA. This was compared with results from a similar survey undertaken
in 2006. RESULTS: Seventy-nine GPs returned questionnaires (response rate 35%).
GP recommendations for paracetamol, a paracetamol/codeine compound, and oral non
steroidal anti-inflammatory drugs (NSAIDs) were consistent with recommendations
in the RACGP OA CPG, and varied little from the previous survey. Notably, there
was a marked increase between surveys in GP recommendations for tramadol (p =
0.004) and more potent opioids (p < 0.001). Advice about the adverse effects of
NSAIDs and codeine and how to manage them increased between surveys (p = 0.038
and 0.005, respectively). For all non-pharmacological treatments, there were only
minor changes in the percentage of GP recommendations when compared with the
previous survey, however they remain underutilised. CONCLUSIONS: GPs generally
demonstrated a conservative approach to the treatment of OA, however, the
increased recommendations for more potent opioids warrants further investigation.
Patients should be made aware of the risks of medications through the use of
decision aids, which can provide structured guidance to treatment. Non
pharmacological interventions were not given the importance that is suggested by
clinical practice guidelines.
PMID- 26438325
TI - Direct inhibition of plasmatic renin activity with aliskiren: a promising but
under-investigated therapeutic option for non-diabetic glomerulonephritis.
AB - Non-diabetic glomerulonephritis is a frequent cause of end-stage renal disease.
The use of renin-angiotensin-aldosterone system blockers is a fundamental
therapeutic approach. However, converting enzyme inhibitors (ACE-is) and
angiotensin receptor blockers do not always achieve the desired target of
proteinuria. The induction of the prorenin and renin up-regulation is a possible
explanation. Aliskiren is the first drug acting as direct inhibitor of plasmatic
renin activity, also able to interfere with the prorenin and renin profibrotic
escape. We aimed at reviewing the literature for the assessment of potential
efficacy and safety of aliskiren in the treatment of non-diabetic
glomerulonephritis. The data on this topic are limited; however, we concluded for
a possible usefulness of aliskiren. The renal safety profile appears potentially
acceptable in non-diabetic patients although extreme carefulness, particularly
with respect to long-term renal and cardiovascular tolerability, is recommended.
PMID- 26438326
TI - Comparing the efficacy and safety of 365- and 550-MUm laser fibers in semirigid
ureteroscopic Ho:YAG lithotripsy.
AB - PURPOSE: To compare the efficacy and safety of 365- and 550-MUm Ho:YAG laser
fiber in semirigid ureteroscopic lithotripsy and to identify parameters that may
affect laser energy and time during the procedure. METHODS: A database of 111
patients who undergone a semirigid ureteroscopy (SRURS) for ureteral stone
lithotripsy was analyzed. A 365-MUm core fiber was used in 56 cases, and a
multiple-uses 550-MUm laser fiber was used in 55 cases. A standard 6.4 W protocol
(8 Hz, 0.8 J/pulse) was used in all cases. The association between laser fiber
diameter and several preoperative, intraoperative and postoperative parameters
was evaluated. RESULTS: Mean stone burden was 54.1 +/- 39.1 mm(2), and
postoperative stone-free and complication rate was 100.0 and 16.2 %,
respectively. The 550-MUm laser fiber diameter was significantly associated with
lower laser energy (p = 0.01), energy/mm(3) (p = 0.031), number of pulses (p =
0.012), laser time (p = 0.012) and laser time/mm(3) (p = 0.043), while it did not
affect postoperative outcomes. The multivariate analysis showed that shorter
procedure duration, smaller stone burden and the 550-MUm laser fiber were all
significant independent predictors for decreased laser energy consumption.
CONCLUSION: The 550-MUm laser fiber may decrease laser energy and time during
SRURS lithotripsy with Ho:YAG laser compared to the 365 MUm. Given its lower
cost, it may represent the optimal choice for semirigid procedures.
PMID- 26438324
TI - Pathology and immune reactivity: understanding multidimensionality in pulmonary
tuberculosis.
AB - Heightened morbidity and mortality in pulmonary tuberculosis (TB) are
consequences of complex disease processes triggered by the causative agent,
Mycobacterium tuberculosis (Mtb). Mtb modulates inflammation at distinct stages
of its intracellular life. Recognition and phagocytosis, replication in
phagosomes and cytosol escape induce tightly regulated release of cytokines
[including interleukin (IL)-1, tumor necrosis factor (TNF), IL-10], chemokines,
lipid mediators, and type I interferons (IFN-I). Mtb occupies various lung
lesions at sites of pathology. Bacteria are barely detectable at foci of lipid
pneumonia or in perivascular/bronchiolar cuffs. However, abundant organisms are
evident in caseating granulomas and at the cavity wall. Such lesions follow polar
trajectories towards fibrosis, encapsulation and mineralization or liquefaction,
extensive matrix destruction, and tissue injury. The outcome is determined by
immune factors acting in concert. Gradients of cytokines and chemokines (CCR2,
CXCR2, CXCR3/CXCR5 agonists; TNF/IL-10, IL-1/IFN-I), expression of
activation/death markers on immune cells (TNF receptor 1, PD-1, IL-27 receptor)
or abundance of enzymes [arginase-1, matrix metalloprotease (MMP)-1, MMP-8, MMP
9] drive genesis and progression of lesions. Distinct lesions coexist such that
inflammation in TB encompasses a spectrum of tissue changes. A better
understanding of the multidimensionality of immunopathology in TB will inform
novel therapies against this pulmonary disease.
PMID- 26438327
TI - Open partial nephrectomy: ancient art or currently available technique?
AB - Renal cell carcinoma (RCC) accounts for 3 % of adult solid tumors, with the
highest incidence between 50 and 70 years of age. Nephron-sparing surgery was
initially reserved to patients with small renal masses detected in anatomically
or functionally solitary kidney or in the presence of multiple bilateral tumors
or hereditary forms of RCC, which posed a high risk of developing a tumor in the
contralateral kidney. Nowadays, partial nephrectomy (PN) has grown up to an
established approach for the treatment of small renal masses. In patients with
T1a-staged RCCs, PN has proven to be associated with better survival, long-term
renal function preservation with lower dialysis need or renal transplantation.
Currently, most of the kidney masses are incidentally detected, up to 40 %, with
smaller size due to the widespread use of imaging modalities such as ultrasound,
computed tomography and magnetic resonance. Here we review the role of open PN in
the management of small renal masses particularly focusing on indications,
oncological outcomes and comparison with laparoscopic and robotic PN. Recent
studies demonstrate that PN confers better survival, oncologic equivalence and
lower risk of severe chronic kidney disease compared to radical nephrectomy
becoming then the gold-standard surgical technique, even if increasingly
challenged by laparoscopic and/or robot-assisted partial nephrectomy which in the
hands of experts seems to achieve comparable outcome results albeit with slightly
higher complication rate.
PMID- 26438329
TI - Prevalence of primary headache disorders in Fayoum Governorate, Egypt.
AB - BACKGROUND: There is abundance of epidemiological studies of headache in
developed and western countries; however, data in developing countries and in
Egypt are still lacking. This study aims to detect the prevalence of primary
headache disorders in both urban and rural sectors in Fayoum governorate, Egypt.
METHODS: A total of 2600 subjects were included using multi-stage stratified
systematic random sampling, with respondent rate of 91.3 %. A pre-designed Arabic
version, interviewer-administered, pilot tested structured questionnaire was
developed according to The International Classification of Headache Disorders,
3rd edition (beta version), and this questionnaire was validated and the strength
of agreement in headache diagnosis was good. RESULTS: The 1-year headache
prevalence was 51.4 %, which was more prevalent in urban dwellers. The most
common primary headache type was episodic tension type headache (prevalence; 24.5
%), followed by episodic migraine (prevalence; 17.3 %), both types peaked in
midlife. Headache disorders were more common in females with exception of cluster
headache that showed the expected male dominance. The risk of chronic headache
increased more than one fold and half when the participants were females,
married, and in those with high education. More than 60 % of our participants did
not seek medical advice for their headaches problem; this percentage was higher
in rural areas. CONCLUSIONS: Primary headache disorders are common in Egypt;
prevalence rate was comparable with western countries with exception of episodic
tension headache. Still headache is under-estimated and under-recognized in Egypt
and this problem should be targeted by health care providers.
PMID- 26438328
TI - Diabetic nephropathy: What does the future hold?
AB - The consensus management of diabetic nephropathy (DN) in 2015 involves good
control of glycaemia, dyslipidaemia and blood pressure (BP). Blockade of the
renin-angiotensin-aldosterone system using angiotensin-converting enzyme
inhibitors, angiotensin-2 receptor blockers or mineralocorticoid inhibitors are
key therapeutic approaches, shown to be beneficial once overt nephropathy is
manifest, as either, or both, of albuminuria and loss of glomerular filtration
rate. Some significant additional clinical benefits in slowing the progression of
DN was reported from the Remission clinic experience, where simultaneous
intensive control of BP, tight glycaemic control, weight loss, exercise and
smoking cessation were prioritised in the management of DN. This has not proved
possible to translate to more conventional clinical settings. This review briefly
looks over the history and limitations of current therapy from landmark papers
and expert reviews, and following an extensive PubMed search identifies the most
promising clinical biomarkers (both established and proposed). Many challenges
need to be addressed urgently as in order to obtain novel therapies in the
clinic; we also need to examine what we mean by remission, stability and
progression of DN in the modern era.
PMID- 26438330
TI - Elevated blood pressure and headache disorders in China--associations, under
treatment and implications for public health.
AB - BACKGROUND: Both hypertension (HTN) and headache disorders are highly prevalent
worldwide. Our purpose, in a nationwide study of the Chinese general population,
was to evaluate any association between primary headache disorders and elevated
blood pressure (eBP). We could not collect data on antihypertensive therapy, but
took the view that, whatever such therapy might be taken, eBP was a sign that it
was failing to meet treatment needs. Therefore, as a secondary purpose, important
from the public-health perspective, we would present the prevalence of eBP
(treated or not) as indicative of unmet health-care need in China. METHODS: This
was a questionnaire-based nationwide cross-sectional door-to-door survey using
cluster random-sampling, selecting one adult (18-65 years) per household.
Headache was diagnosed by ICHD-II criteria and eBP as systolic blood pressure
>=140 mmHg and/or diastolic blood pressure >=90 mmHg. Chi-squared test and
multivariate logistic regression analysis were used to assess the strength and
significance of associations. We set significance at P <= 0.05. RESULTS: Of 5,041
survey participants (participation rate 94.1 %), 154 were excluded because of
missing BP data, leaving 4,987 for analysis [mean age: 43.6 +/- 12.8 years; male
2,532 (mean age: 43.4 +/- 12.9 years); female 2,455 (mean age 43.9 +/- 12.8
years)]. There were 466 participants with migraine, 535 with tension type
headache (TTH) and 48 with all causes of headache on >=15 days/month. The
prevalence of eBP was 22.1 % (males 22.9 %, females 21.3 %). No associations of
eBP with any of the headache disorders survived multivariate adjusted analysis.
The demographic and anthropometric variables most strongly associated with eBP
were higher age (AOR 3.7) and being overweight (AOR 2.4), seen in both genders.
Less strong were male gender, lower educational level and urban habitation.
CONCLUSIONS: We found no clear-cut associations between eBP and any headache
disorder. The associations with demographic and anthropometric variables may have
acted as confounders in past reports to the contrary. We did find an alarmingly
high prevalence of eBP, recognizing that this signals substantial under-treatment
in China of a serious condition, and therefore a major public-health concern.
PMID- 26438331
TI - Astrocyte/neuron ratio and its importance on glutamate toxicity: an in vitro
voltammetric study.
AB - The purpose of this study was to clarify the relationship between neuron cells
and astrocyte cells in regulating glutamate toxicity on the 10th and 20th day in
vitro. A mixed primary culture system from newborn rats that contain cerebral
cortex neurons cells was employed to investigate the glutamate toxicity. All
cultures were incubated with various glutamate concentrations, then viability
tests and histological analyses were performed. The activities of glutamate
transporters were determined by using in vitro voltammetry technique. Viable cell
number was decreased significantly on the 10th day at 10(-7) M and at 10(-6) M
glutamate applications, however, viable cell number was not decreased at 20th
day. Astrocyte number was increased nearly six times on the 20th day as compared
to the 10th day. The peak point of glutamate reuptake capacity was about 2 * 10(
4) M on the 10th day and 10(-3) M on the 20th day. According to our results, we
suggested that astrocyte age was important to maintain neuronal survival against
glutamate toxicity. Thus, we revealed activation or a trigger point of glutamate
transporters on astrocytes due to time since more glutamate was taken up by
astrocytes when glutamate transporters on the astrocyte were triggered with high
exogenous glutamate concentrations. In conclusion, the present investigation is
the first voltammetric study on the reuptake parameters of glutamate in vitro.
PMID- 26438332
TI - Growth and refinement of excitatory synapses in the human auditory cortex.
AB - We had earlier demonstrated a neurofilament-rich plexus of axons in the
presumptive human auditory cortex during fetal development which became adult
like during infancy. To elucidate the origin of these axons, we studied the
expression of the vesicular glutamate transporters (VGLUT) 1 and 2 in the human
auditory cortex at different stages of development. While VGLUT-1 expression
predominates in intrinsic and cortico-cortical synapses, VGLUT-2 expression
predominates in thalamocortical synapses. Levels of VGLUT-2 mRNA were higher in
the auditory cortex before birth compared to postnatal development. In contrast,
levels of VGLUT-1 mRNA were low before birth and increased during postnatal
development to peak during childhood and then began to decrease in adolescence.
Both VGLUT-1 and VGLUT-2 proteins were present in the human auditory cortex as
early as 15GW. Further, immunohistochemistry revealed that the supra- and
infragranular layers were more immunoreactive for VGLUT-1 compared to that in
Layer IV at 34GW and this pattern was maintained until adulthood. As for VGLUT-1
mRNA, VGLUT-1 synapses increased in density between prenatal development and
childhood in the human auditory cortex after which they appeared to undergo
attrition or pruning. The adult pattern of VGLUT-2 immunoreactivity (a dense band
of VGLUT-2-positive terminals in Layer IV) also began to appear in the
presumptive Heschl's gyrus at 34GW. The density of VGLUT-2-positive puncta in
Layer IV increased between prenatal development and adolescence, followed by a
decrease in adulthood, suggesting that thalamic axons which innervate the human
auditory cortex undergo pruning comparatively late in development.
PMID- 26438333
TI - Dentatorubrothalamic tract localization with postmortem MR diffusion tractography
compared to histological 3D reconstruction.
AB - Diffusion-weighted imaging (DWI) tractography is a technique with great potential
to characterize the in vivo anatomical position and integrity of white matter
tracts. Tractography, however, remains an estimation of white matter tracts, and
false-positive and false-negative rates are not available. The goal of the
present study was to compare postmortem tractography of the dentatorubrothalamic
tract (DRTT) by its 3D histological reconstruction, to estimate the reliability
of the tractography algorithm in this specific tract. Recent studies have shown
that the cerebellum is involved in cognitive, language and emotional functions
besides its role in motor control. However, the exact working mechanism of the
cerebellum is still to be elucidated. As the DRTT is the main output tract it is
of special interest for the neuroscience and clinical community. A postmortem
human brain specimen was scanned on a 7T MRI scanner using a diffusion-weighted
steady-state free precession sequence. Tractography was performed with
PROBTRACKX. The specimen was subsequently serially sectioned and stained for
myelin using a modified Heidenhain-Woelke staining. Image registration permitted
the 3D reconstruction of the histological sections and comparison with MRI. The
spatial concordance between the two modalities was evaluated using ROC analysis
and a similarity index (SI). ROC curves showed a high sensitivity and specificity
in general. Highest measures were observed in the superior cerebellar peduncle
with an SI of 0.72. Less overlap was found in the decussation of the DRTT at the
level of the mesencephalon. The study demonstrates high spatial accuracy of
postmortem probabilistic tractography of the DRTT when compared to a 3D
histological reconstruction. This gives hopeful prospect for studying structure
function correlations in patients with cerebellar disorders using tractography of
the DRTT.
PMID- 26438334
TI - Long, intrinsic horizontal axons radiating through and beyond rat barrel cortex
have spatial distributions similar to horizontal spreads of activity evoked by
whisker stimulation.
AB - Stimulation of a single whisker evokes a peak of activity that is centered over
the associated barrel in rat primary somatosensory cortex, and yet the evoked
local field potential and the intrinsic signal optical imaging response spread
symmetrically away from this barrel for over 3.5 mm to cross cytoarchitectonic
borders into other "unimodal" sensory cortical areas. To determine whether long
horizontal axons have the spatial distribution necessary to underlie this
activity spread, we injected adeno-associated viral vectors into barrel cortex
and characterized labeled axons extending from the injection site in transverse
sections of flattened cortex. Combined qualitative and quantitative analyses
revealed labeled axons radiating diffusely in all directions for over 3.5 mm from
supragranular injection sites, with density declining over distance. The
projection pattern was similar at four different cortical depths, including
infragranular laminae. Infragranular vector injections produced patterns similar
to the supragranular injections. Long horizontal axons were detected both using a
vector with a permissive cytomegalovirus promoter to label all neuronal subtypes
and using a calcium/calmodulin-dependent protein kinase II alpha vector to
restrict labeling to excitatory cortical pyramidal neurons. Individual axons were
successfully reconstructed from series of supragranular sections, indicating that
they traversed gray matter only. Reconstructed axons extended from the injection
site, left the barrel field, branched, and sometimes crossed into other sensory
cortices identified by cytochrome oxidase staining. Thus, radiations of long
horizontal axons indeed have the spatial characteristics necessary to explain
horizontal activity spreads. These axons may contribute to multimodal cortical
responses and various forms of cortical neural plasticity.
PMID- 26438335
TI - The KT Jeang Retrovirology prize 2015: Paul Bieniasz.
PMID- 26438337
TI - Erratum to: A Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis in
Patients with Suspected Type 3 Sphincter of Oddi Dysfunction.
PMID- 26438336
TI - The relationship between parenting stress and parent-child interaction with
health outcomes in the youngest patients with type 1 diabetes (0-7 years).
AB - To test whether parenting stress and the quality of parent-child interaction were
associated with glycemic control and quality of life (QoL) in young children (0-7
years) with type 1 diabetes (T1DM), we videotaped 77 families with a young child
with T1DM during mealtime (including glucose monitoring and insulin
administration). Parent-child interactions were scored with a specifically
designed instrument. Questionnaires assessed general and disease-related
parenting stress and (diabetes-specific (DS)) QoL. HbA(1c) (glycemic control) was
extracted from the medical records. Both general and disease-related parenting
stress were associated with a lower (DS)QoL (r ranged from -0.39 to -0.70, p <
0.05), but not with HbA(1c) levels. Furthermore, with regard to the parent-child
interaction, emotional involvement of parents (r = 0.23, p < 0.05) and expressed
discomfort of the child (r = 0.23, p < 0.05) were related to suboptimal HbA(1c)
levels. There was no clear pattern in the correlations between parent-child
interaction and (DS)QoL. CONCLUSION: The results support the notion that diabetes
does not only affect the child with T1DM: T1DM is a family disease, as parenting
factors (like stress and parent-child interactions) are associated with important
child outcomes. Therefore, it is important for health-care providers to not only
focus on the child with T1DM, but also on the family system.
PMID- 26438338
TI - Plasma pharmacokinetic profile of fluralaner (BravectoTM) and ivermectin
following concurrent administration to dogs.
AB - BACKGROUND: Fluralaner is a novel systemic ectoparasiticide for dogs providing
immediate and persistent flea, tick and mite control after a single oral dose.
Ivermectin has been used in dogs for heartworm prevention and at off label doses
for mite and worm infestations. Ivermectin pharmacokinetics can be influenced by
substances affecting the p-glycoprotein transporter, potentially increasing the
risk of ivermectin neurotoxicity. This study investigated ivermectin blood plasma
pharmacokinetics following concurrent administration with fluralaner. FINDINGS:
Ten Beagle dogs each received a single oral administration of either 56 mg
fluralaner (BravectoTM), 0.3 mg ivermectin or 56 mg fluralaner plus 0.3 mg
ivermectin/kg body weight. Blood plasma samples were collected at multiple post
treatment time points over a 12-week period for fluralaner and ivermectin plasma
concentration analysis. Ivermectin blood plasma concentration profile and
pharmacokinetic parameters Cmax, tmax, AUCinfinity and t1/2 were similar in dogs
administered ivermectin only and in dogs administered ivermectin concurrently
with fluralaner, and the same was true for fluralaner pharmacokinetic parameters.
CONCLUSIONS: Concurrent administration of fluralaner and ivermectin does not
alter the pharmacokinetics of either compound. Based on the plasma
pharmacokinetic profile and the clinical observations, there is no evident
interaction between fluralaner and ivermectin, and co-administration does not
increase the risk of ivermectin associated neurotoxicity.
PMID- 26438339
TI - Gene loss, adaptive evolution and the co-evolution of plumage coloration genes
with opsins in birds.
AB - BACKGROUND: The wide range of complex photic systems observed in birds
exemplifies one of their key evolutionary adaptions, a well-developed visual
system. However, genomic approaches have yet to be used to disentangle the
evolutionary mechanisms that govern evolution of avian visual systems. RESULTS:
We performed comparative genomic analyses across 48 avian genomes that span
extant bird phylogenetic diversity to assess evolutionary changes in the 17
representatives of the opsin gene family and five plumage coloration genes. Our
analyses suggest modern birds have maintained a repertoire of up to 15 opsins.
Synteny analyses indicate that PARA and PARIE pineal opsins were lost, probably
in conjunction with the degeneration of the parietal organ. Eleven of the 15
avian opsins evolved in a non-neutral pattern, confirming the adaptive importance
of vision in birds. Visual conopsins sw1, sw2 and lw evolved under negative
selection, while the dim-light RH1 photopigment diversified. The evolutionary
patterns of sw1 and of violet/ultraviolet sensitivity in birds suggest that avian
ancestors had violet-sensitive vision. Additionally, we demonstrate an adaptive
association between the RH2 opsin and the MC1R plumage color gene, suggesting
that plumage coloration has been photic mediated. At the intra-avian level we
observed some unique adaptive patterns. For example, barn owl showed early signs
of pseudogenization in RH2, perhaps in response to nocturnal behavior, and
penguins had amino acid deletions in RH2 sites responsible for the red shift and
retinal binding. These patterns in the barn owl and penguins were convergent with
adaptive strategies in nocturnal and aquatic mammals, respectively. CONCLUSIONS:
We conclude that birds have evolved diverse opsin adaptations through gene loss,
adaptive selection and coevolution with plumage coloration, and that
differentiated selective patterns at the species level suggest novel photic
pressures to influence evolutionary patterns of more-recent lineages.
PMID- 26438340
TI - NF-kappaB Blockade in Hypothalamic Paraventricular Nucleus Inhibits High-Salt
Induced Hypertension Through NLRP3 and Caspase-1.
AB - High-salt-induced inflammation and oxidative stress in the hypothalamic
paraventricular nucleus (PVN) contribute to the pathogenesis of salt-sensitive
hypertension. In this study, we hypothesized that chronic inhibition of nuclear
factor-kappaB (NF-kappaB) activity in the PVN delays the progression of
hypertension by upregulating anti-inflammatory cytokines, reducing NLRP3 (NOD
like receptor family pyrin domain containing 3) and IL-1beta and attenuating p
IKKbeta, NF-kappaB p65 activity and NAD(P)H oxidase in the PVN of salt-sensitive
hypertensive rats. Dahl salt-sensitive rats received a high-salt diet (HS, 8 %
NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks and were treated with
bilateral PVN infusion with either vehicle or pyrrolidine dithiocarbamate (PDTC,
5 MUg/h), a NF-kappaB inhibitor via osmotic minipump. The mean arterial pressure
and plasma levels of norepinephrine (NE) and epinephrine (EPI) were significantly
increased in high-salt-fed rats. In addition, rats with high-salt diet had higher
levels of p-IKKbeta, NF-kappaB p65 activity, Fra-like (Fra-LI) activity (an
indicator of chronic neuronal activation), NOX-4 (subunits of NAD(P)H oxidase),
NLRP3 and IL-1beta, and lower levels of IL-10 in the PVN than normal diet rats.
Bilateral PVN infusions of PDTC attenuated these high-salt-induced changes. These
findings suggest that high-salt-induced NF-kappaB activation in the PVN caused
hypertension via sympathoexcitation, which are associated with the increases of
NLRP3, IL-1beta and oxidative stress in the PVN; PVN inhibition of NF-kappaB
activity attenuates NLRP3, IL-1beta and oxidative stress in the PVN and thereby
attenuates hypertension.
PMID- 26438341
TI - Erratum to: Synchronization in the Heart Rate and the Vasomotion in Rat Aorta:
Effect of Arsenic Trioxide.
PMID- 26438342
TI - Diagnostics barriers and innovations in rural areas: insights from junior medical
doctors on the frontlines of rural care in Peru.
AB - BACKGROUND: Worldwide, rural communities face barriers when accessing health
services. In response, numerous initiatives have focused on fostering
technological innovations, new management approaches and health policies.
Research suggests that the most successful innovations are those involving
stakeholders at all levels. However, there is little evidence exploring the
opinions of local health providers that could contribute with further innovation
development and research. The aims of this study were to explore the perspectives
of medical doctors (MDs) working in rural areas of Peru, regarding the barriers
impacting the diagnostic process, and ideas for diagnostic innovations that could
assist them. METHODS: Data gathered through three focus group discussions (FGG)
and 18 individual semi-structured interviews (SSI) with MDs who had completed
their medical service in rural areas of Peru in the last two years were analyzed
using thematic analysis. RESULTS: Three types of barriers emerged. The first
barrier was the limited access to point of care (POC) diagnostic tools. Tests
were needed for: i) the differential diagnosis of malaria vs. pneumonia, ii)
dengue vs. leptospirosis, iii) tuberculosis, iv) vaginal infections and cervical
cancer, v) neurocysticercosis, and vi) heavy metal toxicity. Ultrasound was
needed for the diagnosis of obstetric and intra-abdominal conditions. There were
also health system-related barriers such as limited funding for diagnostic
services, shortage of specialists, limited laboratory services and access to
telecommunications, and lack of institutional support. Finally, the third type of
barriers included patient related-barriers to follow through with diagnostic
referrals. Ideas for innovations proposed included POC equipment and tests, and
telemedicine. CONCLUSIONS: MDs at primary health facilities in rural Peru face
diagnostic challenges that are difficult to overcome due to a limited access to
diagnostic tools. Referrals to specialized facilities are constrained by
deficiencies in the organization of health services and by barriers that impede
the patients' travel to distant health facilities. Technological innovations
suggested by the participants such as POC diagnostic tools and mobile-health (m
health) applications could help address part of the problem. However, other types
of innovation to address social, adaptation and policy issues should not be
dismissed.
PMID- 26438344
TI - Multifractal spectrum and lacunarity as measures of complexity of
osseointegration.
AB - OBJECTIVES: The goal of this study is to contribute to a better quantitative
description of the early stages of osseointegration, by application of fractal,
multifractal, and lacunarity analysis. MATERIALS AND METHODS: Fractal,
multifractal, and lacunarity analysis are performed on scanning electron
microscopy (SEM) images of titanium implants that were first subjected to
different treatment combinations of i) sand blasting, ii) acid etching, and iii)
exposition to calcium phosphate, and were then submersed in a simulated body
fluid (SBF) for 30 days. All the three numerical techniques are applied to the
implant SEM images before and after SBF immersion, in order to provide a
comprehensive set of common quantitative descriptors. RESULTS: It is found that
implants subjected to different physicochemical treatments before submersion in
SBF exhibit a rather similar level of complexity, while the great variety of
crystal forms after SBF submersion reveals rather different quantitative measures
(reflecting complexity), for different treatments. In particular, it is found
that acid treatment, in most combinations with the other considered treatments,
leads to a higher fractal dimension (more uniform distribution of crystals),
lower lacunarity (lesser variation in gap sizes), and narrowing of the
multifractal spectrum (smaller fluctuations on different scales). CONCLUSION: The
current quantitative description has shown the capacity to capture the main
features of complex images of implant surfaces, for several different treatments.
Such quantitative description should provide a fundamental tool for future large
scale systematic studies, considering the large variety of possible implant
treatments and their combinations. CLINICAL RELEVANCE: Quantitative description
of early stages of osseointegration on titanium implants with different
treatments should help develop a better understanding of this phenomenon, in
general, and provide basis for further systematic experimental studies. Clinical
practice should benefit from such studies in the long term, by more ready access
to implants of higher quality.
PMID- 26438343
TI - Longevity of resin-bonded fixed partial dental prostheses made with metal alloys.
AB - OBJECTIVES: The purpose of this study was to evaluate the clinical performance of
resin-bonded fixed partial dental prostheses (RBFPDPs) made with metal alloys.
MATERIALS AND METHODS: The retention of 311 RBFPDPs from 226 patients fabricated
from 1983 to 2013 using an adhesive resin was clinically evaluated. Partial or
complete debonding of the RBFPDP or framework fracture was considered a treatment
failure. All data were obtained from clinical examinations, and missing data were
censored at the date of the last available information. The effect of the
following factors on survival rate were investigated: patient gender, location
(maxilla/mandible and anterior/posterior), number of missing teeth, number of
abutment teeth, framework structure, type of metal alloy, patient age at the
point of cementation, cement type, and distinction of the treating dentist. Data
were analyzed with the Kaplan-Meier survival tests, log-rank tests, and Cox
regression analyses (alpha = 0.05). RESULTS: The Kaplan-Meier survival rate was
41.2 % +/- 6.5 % (standard error) at 28.8 years (last outcome event). Significant
differences were found for patient age and treating dentist (p < 0.05). The risk
of failure in younger patients was 1.7 times greater than that in older patients
and that of inexperienced dentists was 2.0 times greater than that of dentist
experienced and specialized in adhesive dentistry. CONCLUSIONS: When fabricating
RBFPDPs for younger patients, mechanical preparation for bonding may be necessary
in consideration of the risk for debonding. Experienced dentists may achieve
better results. CLINICAL RELEVANCE: Mastery of skills is necessary to ensure
excellent prognoses for RBFPDPs.
PMID- 26438345
TI - Mortality in Rheumatoid Arthritis (RA): factors associated with recording RA on
death certificates.
AB - BACKGROUND: Death certificates can be used to assess disease prevalence and
incidence; however, rheumatoid arthritis (RA) often remains unreported in death
certificates. We sought to determine to what extent RA is underreported and what
demographic and clinical characteristics could predict mention of RA in the death
certificate. METHODS: We recruited 1328 patients with RA from private, public and
military rheumatology practices and followed them prospectively for yearly
evaluations. A rheumatologist assessed clinical characteristics of RA and
comorbidities at each evaluation. Deaths were identified through family members,
other physicians, obituaries and public death databases. All were confirmed with
state-issued death certificates. Patients with and without RA in death
certificate were compared using bivariate and multivariate analyses. RESULTS: By
December 2013, 326 deaths had occurred. We received and reviewed death
certificates for all confirmed deaths, of which 58 (17.7 %) mentioned RA on the
death certificate. Bivariate analysis revealed that younger age, a greater number
of deformities, higher Sharp score and lower socioeconomic status were each
associated with recording RA. Multivariable analyses revealed that comorbidity
[OR (95 % CI) = 0.84 (0.73, 0.97); P = 0.022] was inversely associated with
listing RA on the death certificate, while the number of deformities [OR (95 %
CI) = 1.04 (1.00, 1.07); P = 0.033] and a certified physician's signature on the
death certificate [OR (95 % CI) = 4.79 (1.35, 16.9); P = 0.015] increased
likelihood of reporting RA. CONCLUSION: In this cohort, RA was not listed in over
80 % of death certificates. Younger patients with fewer comorbidities and more
joint deformities were more likely to have RA reported. DISCUSSION: RA is often
not included in death certificates. The findings of this study suggest that older
patients may have a greater number of comorbidities, thus decreasing the
likelihood that RA be included when completing the death certificate.
PMID- 26438346
TI - "Short term surgical complications after subthalamic deep brain stimulation for
Parkinson's disease: does old age matter?".
AB - BACKGROUND: Patients aged 65 years and older are not traditionally considered
optimal candidates for subthalamic deep brain stimulation (STN-DBS), mainly for
their presumed increased incidence of surgical complications. The aim of this
study was to assess STN-DBS surgery safety in relation to age. METHODS: A total
of 107 consecutive patients undergoing bilateral STN-DBS at our institution
between 2002 and 2014 were retrospectively stratified according to age in two
groups (Young group < 65 years old; Elderly group >= 65 years old;). Rate of
short-term surgical complications (within 90 days) was reviewed and compared
between the two groups. RESULTS: Pre-operative baseline data were comparable
between the two groups. The 90-days post-operative mortality rate was 0%. Overall
incidence of complications related to surgery was 6,54%. In the Elderly group we
observed 3 post-operative intra-cerebral haematomas (7,89%), 1 requiring urgent
surgical evacuation. In the Young group we observed 2 post-operative asymptomatic
intra-cerebral haematomas (2,89%) and 2 wound infections (2,89%), 1 requiring
system removal. No others surgical complications were noticed in both groups.
CONCLUSIONS: Chronological age >= 65 years old should not be considered alone as
exclusion criteria to STN-DBS surgery.
PMID- 26438347
TI - Inhomogeneous myocardial stress perfusion in SPECT studies predicts future
allograft dysfunction in heart transplant recipients.
AB - BACKGROUND: Myocardial perfusion gated single photon emission computed tomography
(SPECT) can be used for non-invasive detection of coronary artery stenosis and
cardiac allograft vasculopathy (CAV), which is a crucial factor for the long-term
survival of heart transplant (HTx) recipients. A frequently observed finding in
myocardial perfusion imaging of patients after HTx is inhomogeneous myocardial
perfusion. This finding is not associated with epicardial CAV, but its prognostic
relevance is unclear so far. We therefore evaluated the prognosis of patients
with homogeneous versus inhomogeneous myocardial stress perfusion. METHODS: One
hundred four HTx patients (mean 3.6 +/- 2.9 years after HTx) without significant
stress-induced ischemia (summed stress score <=3) in gated SPECT and without CAV
were included. Myocardial stress perfusion was visually assessed as homogeneous,
moderately, or severely inhomogeneous. The mean follow-up period after SPECT was
9.4 +/- 3.1 years. End points were the diagnosis of CAV, major cardiac events
(MACE) or death, and the development of allograft dysfunction (left ventricular
ejection fraction, LVEF <45 %). RESULTS: Of all HTx patients, 24 % enrolled in
this study (n = 25) presented with inhomogeneous myocardial perfusion. Compared
to the patients with homogeneous perfusion, these patients were at higher risk
for developing allograft dysfunction (multivariate hazard ratio, HR = 5.59). As
to the development of CAV, the occurrence of MACE, or death, no statistical
differences were observed between patients with homogenous and inhomogeneous
perfusion. There was no correlation between myocardial perfusion pattern and
prior cardiac allograft rejections. CONCLUSIONS: Inhomogeneous myocardial stress
perfusion in SPECT studies predicts a higher risk for future development of
allograft dysfunction in HTx patients (LVEF <45 %) but is not associated with
future CAV, MACE, or overall survival.
PMID- 26438348
TI - A longitudinal daily diary analysis of condom use during bleeding-associated
vaginal sex among adolescent females.
AB - OBJECTIVE: Sex during bleeding is a risk factor for sexually transmitted
infection (STI) and other bloodborne viruses, including HIV. We examined daily
predictors of adolescent women's male condom use during bleeding-associated
vaginal sex. METHODS: Adolescent females (N=387; 14-17 years) were recruited from
primary care clinics for a longitudinal cohort study of STIs and sexual
behaviour. Data were daily partner-specific sexual diaries; generalised
estimating equation logistic regression assessed the likelihood of condom use
during bleeding-associated vaginal sex. RESULTS: Less than 30% of bleeding
associated vaginal sex events were condom protected. Condom use during these
events was less likely with younger age, higher partner support, higher partner
negativity or past week bleeding-associated sex with a given partner; condom use
was more likely with high individual mood and past week condom use during
bleeding-associated vaginal sex with a given partner. CONCLUSIONS: Low condom
rates during bleeding-associated vaginal sex can increase STI and bloodborne
virus risk. Providers should consider integrating partner-specific and
behavioural factors when they deliver sexual health messages to young women.
PMID- 26438349
TI - Does integration of HIV and SRH services achieve economies of scale and scope in
practice? A cost function analysis of the Integra Initiative.
AB - OBJECTIVE: Policy-makers have long argued about the potential efficiency gains
and cost savings from integrating HIV and sexual reproductive health (SRH)
services, particularly in resource-constrained settings with generalised HIV
epidemics. However, until now, little empirical evidence exists on whether the
hypothesised efficiency gains associated with such integration can be achieved in
practice. METHODS: We estimated a quadratic cost function using data obtained
from 40 health facilities, over a 2-year-period, in Kenya and Swaziland. The
quadratic specification enables us to determine the existence of economies of
scale and scope. FINDINGS: The empirical results reveal that at the current
output levels, only HIV counselling and testing services are characterised by
service-specific economies of scale. However, no overall economies of scale exist
as all outputs are increased. The results also indicate cost complementarities
between cervical cancer screening and HIV care; post-natal care and HIV care and
family planning and sexually transmitted infection treatment combinations only.
CONCLUSIONS: The results from this analysis reveal that contrary to expectation,
efficiency gains from the integration of HIV and SRH services, if any, are likely
to be modest. Efficiency gains are likely to be most achievable in settings that
are currently delivering HIV and SRH services at a low scale with high levels of
fixed costs. The presence of cost complementarities for only three service
combinations implies that careful consideration of setting-specific clinical
practices and the extent to which they can be combined should be made when
deciding which services to integrate. TRIAL REGISTRATION NUMBER: NCT01694862.
PMID- 26438350
TI - Common Iliac Artery Aneurysm Repair Using a Sac-Anchoring Endograft to Preserve
the Internal Iliac Artery.
AB - PURPOSE: To report the application of the Nellix endovascular aneurysm sealing
system to successfully treat a unilateral common iliac aneurysm and preserve the
internal iliac artery. CASE REPORT: An 85-year-old man presented with right-sided
necrosis of the third and fourth toe. Computed tomography angiography (CTA)
showed a right 40-mm popliteal aneurysm and a 38-mm left fusiform common iliac
artery aneurysm. After endovascular exclusion of the popliteal aneurysm, the
Nellix device was positioned to exclude the common iliac artery aneurysm while
preserving the internal iliac artery. Postoperative CTA showed no endoleak and a
patent internal iliac artery. At 1 year, duplex ultrasound documented a common
iliac aneurysm diameter of 32 mm without complications. CONCLUSION: Endovascular
sealing using the Nellix device can be applied to exclude selected common iliac
artery aneurysms with an adequate length and a minimal distal neck, with
preservation of the internal iliac artery. The endobag can be positioned such
that the aneurysm is completely excluded while the orifice of the side branch is
not endangered.
PMID- 26438351
TI - Five-Year Outcome of Self-Expanding Covered Stents for Superficial Femoral Artery
Occlusive Disease and an Analysis of Factors Predicting Failure.
AB - PURPOSE: To investigate the 5-year outcome of patients treated with self
expanding covered stents for superficial femoral artery (SFA) occlusive disease
and identify parameters that could predict loss of primary patency. METHODS: In a
dual-center study, 315 consecutive patients (mean age 69.0+/-10.1 years; 232 men)
treated for SFA occlusive disease in 334 limbs with Viabahn self-expanding
covered stents between 2001 and 2014 were retrospectively analyzed. Mean lesion
length was 11.7+/-8.8 cm, and half of the lesions were classified as TASC II C/D.
Five-year patency rates were calculated, and Cox regression analyses were
performed to assess potential factors affecting patency. RESULTS: All-cause
mortality at 5 years was 14.1%. Primary patency rates at 1, 3, and 5 years were
72.2%, 51.8%, and 47.6%, respectively, with secondary patency rates of 86.2%,
78.7%, and 77.5%. Parameters predicting loss of primary patency in a univariate
analysis were covered stent diameter (p=0.001), the number of covered stents per
lesion (p=0.015), and TASC II D classification (p=0.007). Covered stent diameter
was the only parameter predicting loss of primary patency in the multivariate
regression analysis (p=0.001), with 7-mm covered stents having superior
performance. CONCLUSION: Five-year patency rates of self-expanding covered stents
inserted for SFA occlusive disease are within an acceptable range. Covered stent
diameter is the most relevant factor in predicting loss of primary patency, and
thus, an adequate diameter of the distal landing site seems to be among the most
important factors in the decision-making process. In smaller vessels, one should
not use covered stents but venous conduits, as oversizing may be detrimental.
PMID- 26438352
TI - Relationship Between Primary Patency and Lesion Length Following Bare Nitinol
Stent Placement for Femoropopliteal Disease.
AB - PURPOSE: To evaluate the relationship between 1-year primary patency and lesion
length in patients with femoropopliteal disease treated with bare nitinol stents.
METHODS: The study was a retrospective analysis of a prospectively maintained
multicenter database. Between January 2004 and December 2011, 1047 consecutive
patients (mean age 72 years; 765 men) underwent femoropopliteal stenting with
nitinol stents in 1373 limbs. The mean vessel diameter was 5.3+/-0.7 mm and the
mean lesion length was 142+/-75 mm. One-year follow-up data were collected and
analyzed to ascertain which lesion length would be expected to demonstrate a 1
year primary patency above the established 66% objective performance goal (OPG).
RESULTS: The lower limit of the 95% confidence interval (CI) for the unadjusted 1
year primary patency was >66% when the lesion length was <=243 mm. After
adjustment of the covariates to match those of the OPG-derived population, the 1
year primary patency decreased linearly with longer lesion length. The 1-year
primary patency was 83.2% (95% CI 79.8% to 86.1%) for a 100-mm lesion length,
76.4% (95% CI 71.7% to 80.5%) for a 200-mm lesion length, and 70.7% (95% CI 62.4%
to 77.7%) for a 300-mm lesion length. The maximum lesion length providing a 1
year primary patency significantly greater than 66% was calculated to be 263 mm.
CONCLUSION: The 1-year primary patency of femoropopliteal lesions treated with
bare nitinol stents decreased linearly with longer lesion length. The maximum
lesion length providing a higher patency rate than the OPG of 66% was ~25 cm.
PMID- 26438353
TI - Malignant teratoma in Klippel-Feil syndrome: a case report and review of the
literature.
AB - INTRODUCTION: Klippel-Feil syndrome is characterized by a congenital fusion of
cervical vertebrae. Intracranial teratomas are nongerminomatous germ cell tumors
and they account for 0.3 to 0.9% of all intracranial tumors. Teratomas with
malignant transformation refer to lesions which give rise to malignant cancer of
somatic type. The association between tumors of dermoid origin and Klippel-Feil
malformation is extremely rare. Only 23 other cases have so far been reported,
and only one case of dermoid tumor with areas of dedifferentiation on squamous
cell carcinoma has been described. CASE PRESENTATION: We report the case of a 72
year-old white man with a 2-year history of gait and balance disturbances. A
brain magnetic resonance imaging revealed a fourth ventricle neoplastic process
with infiltrative features. He was operated through a suboccipital craniectomy
with a C1 laminotomy and bilateral vertebral artery transposition. At 6-months
follow-up, magnetic resonance imaging showed an early regrowth of the fourth
ventricle tumor, with the same radiological features. CONCLUSIONS: Patients with
Klippel-Feil malformation could develop posterior fossa dermoid tumors. The
malignant potential of such tumors must be considered and surgery is recommended.
Particular attention must be focused on the histopathological analysis in order
to identify possible foci of malignant transformation.
PMID- 26438354
TI - Uptake of risk-reducing salpingo-oophorectomy among female BRCA mutation
carriers: experience at the National Cancer Center of Korea.
AB - PURPOSE: The aim of this study was to identify the uptake rate of risk-reducing
salpingo-oophorectomy (RRSO) and the factors affecting this rate among female
BRCA1 or BRCA2 mutation carriers at the National Cancer Center of Korea. METHODS:
Between April 2007 and December 2014, 450 women underwent BRCA gene testing, and
97 women were found to have BRCA1/2 mutations. Through the review of medical
records, 42 candidates for RRSO were identified. Of these, 22 underwent RRSO.
Demographic, clinical, and consultation-related factors were compared between the
RRSO and non-RRSO groups. RESULTS: The uptake rate of RRSO was 52.4 %. The mean
time interval between genetic testing and surgery in the RRSO group was 7.3
months (range 0.6-33.9). The prevalence of amenorrhea was greater in the RRSO
group than in the non-RRSO group (59.1 % vs. 20.0 %; P = 0.010). More women in
the RRSO group were consulted with gynecologic oncologists (95.5 % vs. 60.0 %; P
= 0.008). In multivariate analyses, amenorrhea at the time of genetic counseling
(OR 16.44; 95 % CI 1.16-232.82; P = 0.038) and consultation with gynecologic
oncologists (OR 30.78; 95 % CI 1.34-707.21; P = 0.032) were identified as factors
affecting the carrier's decision to undergo RRSO. One patient in the non-RRSO
group (5.0 %) developed primary peritoneal carcinoma, which was diagnosed 4.6
years after genetic testing. CONCLUSIONS: The uptake rate of RRSO among BRCA1/2
mutation carriers was affected by the presence of amenorrhea and consultation
with gynecologic oncologists. Gynecologic oncologists with clinical experience
with ovarian cancer should play a major role in aiding carriers' decision-making
concerning RRSO.
PMID- 26438355
TI - Does acute lead (Pb) contamination influence membrane fatty acid composition and
freeze tolerance in intertidal blue mussels in arctic Greenland?
AB - In their natural habitats, organisms are exposed to multiple stressors. Heavy
metal contamination stresses the cell membrane due to increased peroxidation of
lipids. Likewise, sub-zero air temperatures potentially reduce membrane
functionality in ectothermal animals. We tested if acute lead (Pb) exposure for 7
days would influence survival in intertidal blue mussels (Mytilus edulis) after
exposure to realistic sub-zero air temperatures. A full factorial experiment with
five tissue Pb concentrations between 0 and 3500 MUg Pb/g and six sub-zero
temperatures from 0 to -17 degrees C were used to test the hypothesis that sub
lethal effects of Pb may increase the lethality caused by freezing in blue
mussels exposed to temperatures simulating Greenland winter conditions. We found
a significant effect of temperature on mortality. However, the short-term
exposure to Pb did not result in any effects of Pb, nor did we find interactions
between Pb and temperature. We analysed the relative abundance of major
phospholipid fatty acids (PLFAs) in the gill tissue, but we found no significant
effect of Pb tissue concentration on PLFA composition. Results suggest that Pb
accumulation has limited effects on freeze tolerance and does not induce membrane
damage in terms of persistent lipid peroxidation.
PMID- 26438356
TI - DNA oxidation and DNA repair in gills of zebra mussels exposed to cadmium and
benzo(a)pyrene.
AB - Freshwater bivalve molluscs are considered as effective indicators of
environmental pollution. The comet assay allows the detection of DNA damage such
as DNA strand breaks and alkali-labile sites. The main oxidative lesion, 8-oxo
7,8-dihydro-2'-deoxyguanosine (8-oxodG), which is a pre-mutagenic lesion, can be
detected by the comet assay coupled with the hOGG1 DNA repair enzyme. With this
modified assay we recently observed that BaP induced 8-oxodG lesions and with the
modified comet-Fpg assay we observed that Cd induced oxidative DNA damage. The
aim of this study was to determine the stability of DNA lesions in Cd and BaP
exposed zebra mussels using the comet-hOGG1 assay. Mussels were exposed for 24 h
to these two chemicals and then placed in clean water for 6 days. We observed
that BaP (7, 12 and 18 ug/L) induced an increase of DNA strand break levels as
soon as 6 h of exposure and that the two highest concentrations of BaP induced a
low level of hOGG1-sensitive sites. After 2 days of depuration, BaP induced DNA
lesions returned to the basal level, indicating an effective DNA repair. Cd (3,
32 and 81 ug/L) induced an increase of the DNA strand break levels and a low
level of hOGG1-sensitive sites. This study revealed that BaP-induced DNA lesions
are repaired more efficiently than Cd-induced DNA lesions. As the level of hOGG1
sensitive sites was increased in Cd and BaP exposed mussels, it seems that these
chemicals induce 8-oxo-dG.
PMID- 26438357
TI - [Small cell structured cell nests of endometrial stroma].
AB - Tissue from endometrial diagnostic curettage material may show small clumps of
stromal cells, which are pushed together (stromal collapse) and present a picture
of glandular and stromal breakdown. This can be misinterpreted as small cell
structured carcinoma, possibly of neuroendocrine or basal cell origin.
Immunohistochemical investigations (e.g. estrogen receptor, epithelial and
neuroendocrine markers and proliferation markers) are helpful in identifying the
correct differential diagnosis.
PMID- 26438359
TI - Cohesin loss alters adult hematopoietic stem cell homeostasis, leading to
myeloproliferative neoplasms.
AB - The cohesin complex (consisting of Rad21, Smc1a, Smc3, and Stag2 proteins) is
critically important for proper sister chromatid separation during mitosis.
Mutations in the cohesin complex were recently identified in a variety of human
malignancies including acute myeloid leukemia (AML). To address the potential
tumor-suppressive function of cohesin in vivo, we generated a series of shRNA
mouse models in which endogenous cohesin can be silenced inducibly. Notably,
silencing of cohesin complex members did not have a deleterious effect on cell
viability. Furthermore, knockdown of cohesin led to gain of replating capacity of
mouse hematopoietic progenitor cells. However, cohesin silencing in vivo rapidly
altered stem cells homeostasis and myelopoiesis. Likewise, we found widespread
changes in chromatin accessibility and expression of genes involved in
myelomonocytic maturation and differentiation. Finally, aged cohesin knockdown
mice developed a clinical picture closely resembling myeloproliferative
disorders/neoplasms (MPNs), including varying degrees of extramedullary
hematopoiesis (myeloid metaplasia) and splenomegaly. Our results represent the
first successful demonstration of a tumor suppressor function for the cohesin
complex, while also confirming that cohesin mutations occur as an early event in
leukemogenesis, facilitating the potential development of a myeloid malignancy.
PMID- 26438360
TI - Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and
regulate bone mass homeostasis.
AB - Bone surfaces attract hematopoietic and nonhematopoietic cells, such as
osteoclasts (OCs) and osteoblasts (OBs), and are targeted by bone metastatic
cancers. However, the mechanisms guiding cells toward bone surfaces are
essentially unknown. Here, we show that the Galphai protein-coupled receptor
(GPCR) EBI2 is expressed in mouse monocyte/OC precursors (OCPs) and its oxysterol
ligand 7alpha,25-dihydroxycholesterol (7alpha,25-OHC) is secreted abundantly by
OBs. Using in vitro time-lapse microscopy and intravital two-photon microscopy,
we show that EBI2 enhances the development of large OCs by promoting OCP
motility, thus facilitating cell-cell interactions and fusion in vitro and in
vivo. EBI2 is also necessary and sufficient for guiding OCPs toward bone
surfaces. Interestingly, OCPs also secrete 7alpha,25-OHC, which promotes
autocrine EBI2 signaling and reduces OCP migration toward bone surfaces in vivo.
Defective EBI2 signaling led to increased bone mass in male mice and protected
female mice from age- and estrogen deficiency-induced osteoporosis. This study
identifies a novel pathway involved in OCP homing to the bone surface that may
have significant therapeutic potential.
PMID- 26438361
TI - Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis.
AB - Cohesin complex members have recently been identified as putative tumor
suppressors in hematologic and epithelial malignancies. The cohesin complex
guides chromosome segregation; however, cohesin mutant leukemias do not show
genomic instability. We hypothesized that reduced cohesin function alters
chromatin structure and disrupts cis-regulatory architecture of hematopoietic
progenitors. We investigated the consequences of Smc3 deletion in normal and
malignant hematopoiesis. Biallelic Smc3 loss induced bone marrow aplasia with
premature sister chromatid separation and revealed an absolute requirement for
cohesin in hematopoietic stem cell (HSC) function. In contrast, Smc3
haploinsufficiency increased self-renewal in vitro and in vivo, including
competitive transplantation. Smc3 haploinsufficiency reduced coordinated
transcriptional output, including reduced expression of transcription factors and
other genes associated with lineage commitment. Smc3 haploinsufficiency
cooperated with Flt3-ITD to induce acute leukemia in vivo, with potentiated Stat5
signaling and altered nucleolar topology. These data establish a dose dependency
for cohesin in regulating chromatin structure and HSC function.
PMID- 26438362
TI - The role of group IIF-secreted phospholipase A2 in epidermal homeostasis and
hyperplasia.
AB - Epidermal lipids are important for skin homeostasis. However, the entire picture
of the roles of lipids, particularly nonceramide lipid species, in epidermal
biology still remains obscure. Here, we report that PLA2G2F, a functionally
orphan-secreted phospholipase A2 expressed in the suprabasal epidermis, regulates
skin homeostasis and hyperplasic disorders. Pla2g2f(-/-) mice had a fragile
stratum corneum and were strikingly protected from psoriasis, contact dermatitis,
and skin cancer. Conversely, Pla2g2f-overexpressing transgenic mice displayed
psoriasis-like epidermal hyperplasia. Primary keratinocytes from Pla2g2f(-) (/-)
mice showed defective differentiation and activation. PLA2G2F was induced by
calcium or IL-22 in keratinocytes and preferentially hydrolyzed ethanolamine
plasmalogen-bearing docosahexaenoic acid secreted from keratinocytes to give rise
to unique bioactive lipids (i.e., protectin D1 and 9S-hydroxyoctadecadienoic
acid) that were distinct from canonical arachidonate metabolites (prostaglandins
and leukotrienes). Ethanolamine lysoplasmalogen, a PLA2G2F-derived marker
product, rescued defective activation of Pla2g2f(-/-) keratinocytes both in vitro
and in vivo. Our results highlight PLA2G2F as a previously unrecognized regulator
of skin pathophysiology and point to this enzyme as a novel drug target for
epidermal-hyperplasic diseases.
PMID- 26438363
TI - Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact
hypersensitivity responses.
AB - Resolvin E1 (RvE1) is a lipid mediator derived from omega3 polyunsaturated fatty
acids that exerts potent antiinflammatory roles in several murine models. The
antiinflammatory mechanism of RvE1 in acquired immune responses has been
attributed to attenuation of cytokine production by dendritic cells (DCs). In
this study, we newly investigated the effect of RvE1 on DC motility using two
photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1
impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in
the draining lymph nodes and effector T cell activation in the skin, which led to
the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced
actin filament reorganization in DCs and increased DC motility by activating
Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results
suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting
cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade.
PMID- 26438364
TI - Influence of phosphate on toxicity and bioaccumulation of arsenic in a soil
isolate of microalga Chlorella sp.
AB - In this study, the toxicity, biotransformation and bioaccumulation of arsenite
and arsenate in a soil microalga, Chlorella sp., were investigated using
different phosphate levels. The results indicated that arsenate was highly toxic
than arsenite to the alga, and the phosphate limitation in growth media greatly
enhanced arsenate toxicity. The uptake of arsenate in algal cells was more than
that of arsenite, and the predominant species in the growth media was arsenate
after 8 days of exposure to arsenite or arsenate, indicating arsenite oxidation
by this microalga. Arsenate reduction was also observed when the alga was
incubated in a phosphate-limiting growth medium. Similar to the process of
biotransformation, the alga accumulated more arsenic when it was exposed to
arsenate and preferably more in a phosphate-limiting condition. Although
phosphate significantly influences the biotransformation and bioaccumulation of
arsenic, the oxidizing ability and higher accumulation capacity of this alga have
great potential for its application in arsenic bioremediation.
PMID- 26438365
TI - Accumulation patterns of Cr in Callitriche organs--qualitative and quantitative
analysis.
AB - The aims of this study were both the qualitative and quantitative analysis of
chromium accumulation in the shoots of Callitriche cophocarpa. This globally
distributed, submersed macrophyte exhibits outstanding Cr phytoremediation
capacity in an aquatic environment. Cr was applied separately for 7 days at two
stable forms as Cr(VI) and Cr(III), known from their diverse physicochemical
properties and toxicities. The maps of Cr depositions in young leaves, mature
leaves, and stems were obtained by micro X-ray fluorescence spectroscopy (MUXRF).
The detailed analysis of XRF maps was done based on Image-Pro PLUS (Media
Cybernetics) software. Cr was accumulated either in trichomes or vascular bundles
in respect to the element speciation and the plant organ. The concentration of Cr
significantly increased in the following order: Cr(VI) mature leaves < Cr(VI)
young leaves = Cr(VI) stems < Cr(III) young leaves <= Cr(III) mature leaves <=
Cr(III) stems. The observed differences in distribution and accumulation of Cr
were correlated with the different reduction potential of Cr(VI) by particular
plant organs. The reduction of Cr(VI) is considered the main detoxification
mechanism of the highly toxic Cr(VI) form. The unique L-band electron resonance
spectrometer (L-band EPR) was applied to follow the reduction of Cr(VI) to
Cr(III) in the studied material.
PMID- 26438366
TI - Temporal variation of nitrogen balance within constructed wetlands treating
slightly polluted water using a stable nitrogen isotope experiment.
AB - Slightly polluted water has become one of the main sources of nitrogen
contaminants in recent years, for which constructed wetlands (CW) is a typical
and efficient treatment. However, the knowledge about contribution of individual
nitrogen removal pathways and nitrogen balance in constructed wetlands is still
limited. In this study, a stable-isotope-addition experiment was performed in
laboratory-scale constructed wetlands treating slightly polluted water to
determine quantitative contribution of different pathways and temporal variation
of nitrogen balance using Na(15)NO3 as tracer. Microbial conversion and substrate
retention were found to be the dominant pathways in nitrogen removal contributing
24.4-79.9 and 8.9-70.7 %, respectively, while plant contributed only 4.6-11.1 %
through direct assimilation but promoted the efficiency of other pathways. In
addition, microbial conversion became the major way to remove N whereas nitrogen
retained in substrate at first was gradually released to be utilized by microbes
and plants over time. The findings indicated that N2 emission representing
microbial conversion was not only the major but also permanent nitrogen removal
process, thus keeping a high efficiency of microbial conversion is important for
stable and efficient nitrogen removal in constructed wetlands.
PMID- 26438367
TI - Removal of Cd, Cu, Pb, and Zn from aqueous solutions by biochars.
AB - Sorption and desorption of heavy metals (Cd, Cu, Pb, and Zn) was evaluated in
biochars derived from sugarcane bagasse (SB), eucalyptus forest residues (CE),
castor meal (CM), green coconut pericarp (PC), and water hyacinth (WH) as
candidate materials for the treatment of contaminated waters and soils. Solid
liquid distribution coefficients depended strongly on the initial metal
concentration, with K d,max values mostly within the range 10(3)-10(4) L kg(-1).
For all biochars, up to 95 % removal of all the target metals from water was
achieved. The WH biochar showed the highest K d,max values for all the metals,
especially Cd and Zn, followed by CE (for Cd and Pb) and PC (for Cd, Pb, and Zn).
Sorption data were fitted satisfactorily with Freundlich and linear models (in
the latter case, for the low concentration range). The sorption appeared to be
controlled by cationic exchange, together with specific surface complexation at
low metal concentrations. The low desorption yields, generally less than 5 %,
confirmed that the sorption process was largely irreversible and that the
biochars could potentially be used in decontamination applications.
PMID- 26438368
TI - A comparative study of the grain-size distribution of surface dust and stormwater
runoff quality on typical urban roads and roofs in Beijing, China.
AB - The deposition of pollutants on impervious surfaces is a serious problem
associated with rapid urbanization, which results in non-point-source pollution.
Characterizing the build-up and wash-off processes of pollutants in urban
catchments is essential for urban planners. In this paper, the spatial variation
and particle-size distributions of five heavy metals and two nutrients in surface
dust were analyzed, and the runoff water first-flush effect (FF30) and event-mean
concentrations (EMCs) of 10 common constituents were characterized. The
relationships between runoff variables and stormwater characteristics were
examined from three typical urban impervious surfaces in Beijing, China. Dust on
road surfaces with smaller grain sizes had higher pollutant concentrations,
whereas concentrations of Mn, Zn, Fe, and TP in roof surface dust increased with
grain size. Particles with grain sizes of 38-74 and 125-300 MUm contributed most
to the total pollutant load in roads, while particles with the smallest grain
sizes (<38 MUm) contributed most on roofs (23.46-41.71 %). Event-mean
concentrations (EMCs) and FF30 values for most runoff pollutants tended to be
higher on roofs than on roads. The maximum intensity (I max) and the antecedent
dry days (ADD) were critical parameters for EMCs in roads, while ADD was the only
dominant parameter for EMCs on our studied roof. The rainfall intensity (RI) and
maximum intensity (I max) were found to be the parameters with the strongest
correlation to the first-flush effect on both roads and roofs. Significant
correlations of total suspended solids (TSS) concentration in runoff with grain
size fractions of surface dust indicated that coarser particles (74-300 MUm) are
most likely to contribute to the solid-phase pollutants, and finer particles (<38
MUm) are likely the main source of dissolved pollutants.
PMID- 26438369
TI - GC-MS analysis of bioactive components and biosynthesis of silver nanoparticles
using Hybanthus enneaspermus at room temperature evaluation of their stability
and its larvicidal activity.
AB - Green synthesis of silver nanoparticles (AgNPs) using Hybanthus enneaspermus
extract at room temperature that act as a reducing agent as well as capping agent
has been investigated. The synthesized AgNPs were characterized by UV-visible
spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR), zeta
potential, and dynamic light scattering (DLS) transmission electron microscopy
(TEM) and energy-dispersive X-ray (EDX). The silver surface plasmon resonance was
observed at 420 nm in the UV-visible spectrum. XRD peaks were observed at 2theta
values in 38.20 degrees , 44.40 degrees , 64.60 degrees , and 77.50 degrees
which are indexed as (111), (200), (220), and (311) bands of face-centered cubic
(fcc) structures of silver. FTIR revealed the AgNPs were capped with plant
compounds of alcohol, phenols, carbonyl, amines, and amide functional groups. TEM
image shows that the particles were of spherical, hexagonal, and triangular in
shape, and the size range was 16-26 nm. Further, DLS exhibits the average size of
25.2 nm and the zeta values were measured (-27.1 mV) which proves the stability
of the AgNPs. The conversion of Ag(+) ions into Ag(0) was calculated using
inductively coupled plasma atomic emission spectroscopy (ICP-MS) and was found to
be 96 %. The biosynthesized AgNPs showed the larvicidal activity with the LC50
values of 17.24 and 13.12 mg/L against the fourth-instar larvae of Anopheles
subpictus and Culex quinquefasciatus, respectively. The GC-MS analysis of the
plant extract showed that 39 bioactive phytochemical compounds have been found to
possess a wide range of activities, which may help in the protection against
incurable diseases.
PMID- 26438370
TI - Growth and efficiency of nutrient removal by Salix jiangsuensis J172 for
phytoremediation of urban wastewater.
AB - Willows are a group of versatile tree species that may have multiple
environmental applications. In the present study, Salix jiangsuensis J172 plants
were grown in the fixed mats as an economic plant-based treatment system to
evaluate its potential for removing nutrients in wastewater. Plants grew normally
in wastewater compared with those in Hoagland solution. However, wastewater
containing a high concentration of chlorine ions was toxic to S. jiangsuensis
J172 plants. The plants accumulated large amounts of nitrogen and phosphorus in
aboveground tissues under conditions of abundant supply. The removal efficiency
for raw wastewater was 82.18-87.78 % for nitrogen, 57.35-65.58 % for phosphorus,
and 58.24-59.90 % for chemical oxygen demand. Nutrient removal efficiency was
positively correlated with the initial nutrient supply. The results show that S.
jiangsuensis J172 grown in the fixed mat economic plant-based treatment system
with nutrient-rich, eutrophic water may be an effective, low-cost
phytoremediation technology to treat water containing undesirable levels of
wastewater.
PMID- 26438371
TI - Mobilization of trace metals and PCBs from contaminated marine sediments of the
Mar Piccolo in Taranto during simulated resuspension experiment.
AB - The effects of sediment resuspension on the fate of metals and polychlorinated
biphenyls (PCBs) were studied by using a short-term small reactor. Sediments and
water were collected nearby the most contaminated site of the Mar Piccolo of
Taranto. Contaminant partitioning was calculated between the solid and water
phases and, in the latter, between the dissolved and particulate phases and
related to physical-chemical variables. Before and after resuspension, metal
concentrations in sediments did not vary remarkably. Except for Cd, all the
analyzed metals exceeded by many folds both threshold effect level (TEL) and
probable effect level (PEL) SQGs. Igeo index values for Hg designated the
sediment quality as extremely polluted for Pb, Cu and moderately polluted for Zn.
In the dissolved phase, Mn increased of about 70 times, Fe of about 7 times and
Hg and Zn of 4 and 3 times, respectively. PCBs in sediments before and after
resuspension did not vary for more than 15 %. PCB concentrations exceeded for
more than ten times PEL values. After resuspension, PCBs increased from 0.82 to
4.82 ng L(-1) in the dissolved phase and from 0.22 to 202.21 ng L(-1) in the
particulate one. The dissolved phase was initially enriched in light- to mid
weight compounds. After resuspension, the particulate phase was enriched in
heavier congeners. In particular, hexachlorobiphenyl-153, 149 and 138 together
with heptachlorobiphenyl-180 and 187 accounted for 57 % of total PCBs. The
dissolved organic carbon (DOC) that increased from 1.31 to 8.55 mg L(-1) likely
influenced the fate of metals and PCBs in the dissolved and particulate phases.
Despite that the residence time of the contaminated resuspended sediments in the
water column is limited, they are still highly toxic for the pelagic trophic web.
PMID- 26438372
TI - Sorption and degradation of carbaryl in soils amended with biochars: influence of
biochar type and content.
AB - Biochars that were produced from three different biomass materials were amended
to a soil to elucidate their influence on the fate of carbaryl. Sorption and
degradation of carbaryl in soils amended with the biochars were investigated. The
results showed that the amendment of biochars to soil enhanced the sorption of
carbaryl. The nonlinearity of sorption isotherm and sorption affinity of carbaryl
increased with the content and pyrolytic temperature of the biochars. Both
chemical and biological degradation of carbaryl were influenced by biochars. The
biochars enhanced the chemical hydrolysis of carbaryl in soil, with biochars
produced at 700 degrees C (BC700) exhibiting greater impact, due to their strong
liming effect. In contrast, BC350 (produced at 350 degrees C) promoted the
biodegradation of carbaryl in soil by different extents, while BC700 obviously
reduced the biodegradation of carbaryl. The enhanced activities of natural
microorganisms in the soil and the lowered bioavailability of carbaryl acted
together to determine the biodegradation.
PMID- 26438373
TI - Estimation of aerosol optical depth at different wavelengths by multiple
regression method.
AB - This study aims to investigate and establish a suitable model that can help to
estimate aerosol optical depth (AOD) in order to monitor aerosol variations
especially during non-retrieval time. The relationship between actual ground
measurements (such as air pollution index, visibility, relative humidity,
temperature, and pressure) and AOD obtained with a CIMEL sun photometer was
determined through a series of statistical procedures to produce an AOD
prediction model with reasonable accuracy. The AOD prediction model calibrated
for each wavelength has a set of coefficients. The model was validated using a
set of statistical tests. The validated model was then employed to calculate AOD
at different wavelengths. The results show that the proposed model successfully
predicted AOD at each studied wavelength ranging from 340 nm to 1020 nm. To
illustrate the application of the model, the aerosol size determined using
measure AOD data for Penang was compared with that determined using the model.
This was done by examining the curvature in the ln [AOD]-ln [wavelength] plot.
Consistency was obtained when it was concluded that Penang was dominated by fine
mode aerosol in 2012 and 2013 using both measured and predicted AOD data. These
results indicate that the proposed AOD prediction model using routine
measurements as input is a promising tool for the regular monitoring of aerosol
variation during non-retrieval time.
PMID- 26438374
TI - Targeted deletion of Atg5 in chondrocytes promotes age-related osteoarthritis.
AB - OBJECTIVES: It has been suggested that the lysosomal recycling process called
macro-autophagy plays a role in osteoarthritis development. We thus decided to
genetically ablate the autophagy-indispensable Atg5 gene specifically in
chondrocytes and analyse the development of osteoarthritis upon aging and in a
post-traumatic model. METHODS: Mice lacking the Atg5 gene in their chondrocytes
(Atg5cKO) were generated by crossing Atg5-floxed mice with transgenic mice that
expressed cre recombinase driven by the collagen type 2 promoter. Animals were
analysed at the age of 2, 6 and 12 months for age-related osteoarthritis or
underwent mini-open partial medial meniscectomy at 2 months of age and were
analysed 1 or 2 months after surgery. We evaluated osteoarthritis using the
Osteoarthritis Research Society International (OARSI) scoring on safranin-O
stained samples. Cell death was evaluated by terminal deoxy-nucleotidyl
transferase-mediated deoxy-UTP nick end labelling (TUNEL) and by immunostaining
of cleaved caspases. RESULTS: We observed the development of osteoarthritis in
Atg5cKO mice with aging including fibrillation and loss of proteoglycans, which
was particularly severe in males. The ablation of Atg5 was associated with an
increased cell death as assessed by TUNEL, cleaved caspase 3 and cleaved caspase
9. Surprisingly, no difference in the development of post-traumatic
osteoarthritis was observed between Atg5cKO and control mice. CONCLUSIONS:
Autophagy protects from age-related osteoarthritis by facilitating chondrocyte
survival.
PMID- 26438375
TI - Pathogen-regulated genes in wheat isogenic lines differing in resistance to brown
rust Puccinia triticina.
AB - BACKGROUND: Inoculation of wheat plants with Puccinia triticina (Pt) spores
activates a wide range of host responses. Compatible Pt interaction with
susceptible Thatcher plants supports all stages of the pathogen life cycle.
Incompatible interaction with TcLr9 activates defense responses including
oxidative burst and micronecrotic reactions associated with the pathogen's
infection structures and leads to complete termination of pathogen development.
These two contrasting host-pathogen interactions were a foundation for
transcriptome analysis of incompatible wheat-Pt interaction. METHODS: A
suppression subtractive hybridization (SSH) library was constructed using cDNA
from pathogen-inoculated susceptible Thatcher and resistant TcLr9 isogenic lines.
cDNA represented steps of wheat-brown rust interactions: spore germination,
haustorium mother cell (HMC) formation and micronecrotic reactions. All ESTs were
clustered and validated by similarity search to wheat genome using BLASTn and
sim4db tools. qRT-PCR was used to determine transcript levels of selected ESTs
after inoculation in both lines. RESULTS AND DISCUSSION: Out of 793 isolated cDNA
clones, 183 were classified into 152 contigs. 89 cDNA clones and encoded proteins
were functionally annotated and assigned to 5 Gene Ontology categories: catalytic
activity 48 clones (54 %), binding 32 clones (36 %), transporter activity 6
clones (7 %), structural molecule activity 2 clones (2 %) and molecular
transducer activity 1 clone (1 %). Detailed expression profiles of 8 selected
clones were analyzed using the same plant-pathogen system. The strongest
induction after pathogen infection and the biggest differences between resistant
and susceptible interactions were detected for clones encoding wall-associated
kinase (GenBank accession number JG969003), receptor with leucine-rich repeat
domain (JG968955), putative serine/threonine protein kinase (JG968944), calcium
mediated signaling protein (JG968925) and 14-3-3 protein (JG968969). CONCLUSIONS:
The SSH library represents transcripts regulated by pathogen infection during
compatible and incompatible interactions of wheat with P. triticina. Annotation
of selected clones confirms their putative roles in successive steps of plant
pathogen interactions. The transcripts can be categorized as defense-related due
to their involvement in either basal defense or resistance through an R-gene
mediated reaction. The possible involvement of selected clones in pathogen
recognition and pathogen-induced signaling as well as resistance mechanisms such
as cell wall enforcement, oxidative burst and micronecrotic reactions is
discussed.
PMID- 26438377
TI - Efficacy of a referral center for patient-centered care in multiple myeloma: a
cohort study.
AB - BACKGROUND: Within the Brazilian Unified Health System (SUS), Referral Centers
(RCs) are care facilities that provide specialized services. The objective of
this study was to evaluate the efficacy of care provided to patients with
multiple myeloma (MM) at a specialized RC (Hospital de Clinicas de Porto Alegre
Referral Center for Multiple Myeloma, CRMM-HCPA) and to compare quality of life
between patients with MM treated at CRMM-HCPA and those treated at non-RC
facilities. METHODS: A 6-month cohort study was conducted in patients with MM
receiving thalidomide from the Rio Grande do Sul State Health Department and
treated at CRMM-HCPA and patients receiving treatment at other, non-RC care
facilities. Thirty-two patients were included in the study, 19 from CRMM-HCPA and
13 from other institutions. To analyze the efficacy of care provided at CRMM
HCPA, the main outcome measure was the time from diagnosis to referral for
autologous hematopoietic stem cell transplantation (HSCT). This outcome measure
was assessed using questionnaires specifically designed for this study. Quality
of life was also assessed, using the SF-36 questionnaire. RESULTS: Time from MM
diagnosis to referral for autologous HSCT in each group was measured only in
patients aged <= 65 years (n = 25); of these, 15 were recruited from CRMM-HCPA
and 10 from other institutions. In this analysis, there was a significant
difference (p = 0.036) in time elapsed between diagnosis and referral for
autologous HSCT, which was significantly shorter for patients treated at CRMM
HCPA (median, 9 months; IQR, 8.5-14.5) than for those treated elsewhere (median,
24 months; IQR, 16-24). On quality of life analysis, there was a significant
difference in the Social Functioning domain of the SF-36 questionnaire, which
relates to performance of social activities (p = 0.02). CONCLUSIONS: The Referral
Center model provided seems to be a more efficient treatment strategy as compared
with other health care facilities, as it enabled a reduction in time to
transplantation. Patients treated at CRMM-HCPA demonstrated greater ease in
performing social activities, with less interference from physical or emotional
problems.
PMID- 26438376
TI - Comparison of Human Primary with Human iPS Cell-Derived Dopaminergic Neuron
Grafts in the Rat Model for Parkinson's Disease.
AB - Neuronal degeneration within the substantia nigra and the loss of the
dopaminergic nigro-striatal pathway are the major hallmarks of Parkinson's
disease (PD). Grafts of foetal ventral mesencephalic (VM) dopaminergic (DA)
neurons into the striatum have been shown to be able to restore striatal dopamine
levels and to improve overall PD symptoms. However, human foetus-derived cell
grafts are not feasible for clinical application. Autologous induced pluripotent
stem cell (iPS cell)-derived DA neurons are emerging as an unprecedented
alternative. In this review, we summarize and compare the efficacy of human iPS
cell-derived DA neuron grafts to restore normal behaviour in a rat model for PD
with that of human foetal primary DA neurons. The differences we observed in the
efficacy to restore normal function between the 2 types of DA neuron grafts could
be ascribed to intrinsic properties of the iPS cell-derived DA neurons that
critically affected survival and proper neurite extension in the striatum after
implantation.
PMID- 26438378
TI - Halorubrum rutilum sp. nov. isolated from a marine solar saltern.
AB - A halophilic archaeal strain, YJ-18-S1(T), was isolated from Yangjiang marine
solar saltern, Guangxi Province, China. Cells were pleomorphic, stained Gram
negative and formed red-pigmented colonies on agar plates. Strain YJ-18-S1(T) was
able to grow at 20-55 degrees C (optimum 37 degrees C), at 0.9-4.8 M NaCl
(optimum 2.6 M NaCl), at 0.005-1.0 M MgCl2 (optimum 0.3 MgCl2) and at pH 5.5-8.5
(optimum pH 7.0). The cells were lysed in distilled water, and the minimal NaCl
concentration to prevent cell lysis was found to be 5 % (w/v). The major polar
lipids of the strain were phosphatidic acid, phosphatidylglycerol,
phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and
sulfated mannosyl glucosyl diether. The 16S rRNA gene and rpoB' gene of strain YJ
18-S1(T) were phylogenetically related to the corresponding genes of Halorubrum
members (94.3-98.0 and 86.7-96.1 % similarities, respectively). The DNA G+C
content of strain YJ-18-S1(T) was 66.2 mol%. The phenotypic, chemotaxonomic and
phylogenetic properties suggested that strain YJ-18-S1(T) (=CGMCC 1.12554(T) =
JCM 30030(T)) represents a new species of Halorubrum, for which the name
Halorubrum rutilum sp. nov. is proposed.
PMID- 26438379
TI - Comparative study of serum proteomes in Legg-Calve-Perthes disease.
AB - BACKGROUND: Legg-Calve-Perthes Disease (LCPD) is an idiopathic osteonecrosis of
the developing femoral head complicated by pain and disability of the hip joint.
To date, the pathological mechanisms of LCPD are not well-known. This study
screened the changes in serum protein expression in patients with LCPD. METHODS:
Age- and sex-matched serum samples from 10 control subjects and 10 patients with
LCPD were compared using the isobaric tags for relative and absolute
quantification (iTRAQ) technique. Gene ontology analyses, KEGG pathway and
functional network analyses were performed. Proteins of interest with large
differences in expression, S100-A8, alpha-1-acid glycoprotein 1, haptoglobin and
apolipoprotein E, were compared by western blotting. RESULTS: The disease/control
ratios showed 26 proteins were significantly differentially expressed (all p <
0.05). Including higher abundances of complement factor H (1.44), complement C4-B
(1.45), isocitrate dehydrogenase [NAD] subunit alpha (2.7) alpha-1-acid
glycoprotein 1 (1.87), heptoglobin (1.53) and Ig lambda-2 chain C regions (1.46),
and lower levels of apolipoprotein E (0.50), apolipoprotein F (0.60),
apolipoprotein C-III (0.69), S100-A8 (0.73), S100-A9 (0.75) and prothrombin
(0.77) in LCPD than in controls. The alpha-1-acid glycoprotein 1 and haptoglobin
increases, and apolipoprotein E and S100-A8 decreases were confirmed by western
blot. KEGG pathway analysis revealed these proteins were related to the
complement and coagulation cascades, Staphylococcus aureus infection, PPAR
signaling, fat digestion and absorption, and vitamin digestion and absorption.
Functional network analysis suggested that the proteins were involved in lipid
regulation. CONCLUSIONS: The complement and coagulation cascades, and abnormal
lipid metabolism may be involved in the pathogenesis of LCPD.
PMID- 26438380
TI - Reported co-infection deaths are more common in early adulthood and among similar
infections.
AB - BACKGROUND: Many people have multiple infections at the same time, but the
combined contribution of those infections to disease-related mortality is
unknown. Registered causes of death offer a unique opportunity to study
associations between multiple infections. METHODS: We analysed over 900,000 death
certificates that reported infectious causes of death. We tested whether reports
of multiple infections (i.e., co-infections) differed across individuals' age or
sex. We also tested whether each pair of infections were reported together more
or less often than expected by chance, and whether this co-reporting was
associated with the number of biological characteristics they had in common.
RESULTS: In England and Wales, and the USA, 10 and 6 % respectively of infection
related deaths involved co-infection. Co-infection was reported reported most
often in young adults; 30 % of infection-related deaths among those aged 25-44
from the USA, and 20 % of infection-related deaths among those aged 30-39 from
England and Wales, reported multiple infections. The proportion of infection
related deaths involving co-infection declined with age more slowly in males than
females, to less than 10 % among those aged >65. Most associated pairs of
infections co-occurred more often than expected from their frequency of being
reported alone (488/683 [71 %] in the USA, 129/233 [55 %] in England and Wales),
and tended to share biological characteristics (taxonomy, transmission mode,
tropism or timescale). CONCLUSIONS: Age, sex, and biologically similar infections
are associated with death from co-infection, and may help indicate patients at
risk of severe co-infection.
PMID- 26438381
TI - Randomized Questionnaire Based Case-Control Research Study on Evaluation of
Sexual Function in Indian Patients Taking Oral Finasteride for Androgenetic
Alopecia.
AB - INTRODUCTION: Finasteride is one of the most common drugs used in androgenetic
alopecia. The literature discusses the sexual side effects of the drug; however,
in practice there is little evidence to support this. The aim of the present
study was to investigate the sexual dysfunction in patients taking finasteride 1
mg for androgenetic alopecia. METHODS: A questionnaire, based on the
International Index of Erectile Function, was given to approximately 586 patients
with androgenetic alopecia who were being treated with finasteride 1 mg for an
average of 16 weeks. These patients were compared to an age-related control group
who were attending the Dermatology Out Patients Department for various other skin
ailments not related to hair disorders. RESULTS: Statistical analysis of the
results showed no significant difference in the scores between patients taking
finasteride and the control group. CONCLUSION: Analysis showed no significant
difference in sex-related problems with that of patients taking finasteride and
age matched controls, suggesting that sex-related issues are not a side effect of
finasteride.
PMID- 26438383
TI - Metastasized pancreatic neuroendocrine tumor in a teenage girl: a case report.
AB - INTRODUCTION: Metastasized pancreatic neuroendocrine tumors are extremely rare
malignancies, especially in children. Therefore, therapeutic options are limited,
and few standardized therapy regimens exist. CASE PRESENTATION: We report a case
of a 14-year-old white girl. In 2011 she was diagnosed with a metastasized, well
differentiated pancreatic neuroendocrine tumor with expression of synaptophysin
and chromogranin A. We describe her clinical course with special attention to her
individual therapeutic regimens while bringing together several disciplines of
medicine. CONCLUSIONS: In patients such as ours, surgical intervention may be the
only therapy that will lead to long-term survival.
PMID- 26438382
TI - Cognitive flexibility and performance in children and adolescents with threshold
and sub-threshold bipolar disorder.
AB - Greater understanding of cognitive function in children and adolescents with
bipolar disorder (BD) is of critical importance to improve our ability to design
targeted treatments to help with real-world impairment, including academic
performance. We sought to evaluate cognitive performance among children with
either BD type I, II, or "not otherwise specified" (NOS) participating in multi
site Course and Outcome of Bipolar Youth study compared to typically developing
controls (TDC) without psychopathology. In particular, we sought to test the
hypothesis that BD-I and BD-II youths with full threshold episodes of mania or
hypomania would have cognitive deficits, including in reversal learning, vs.
those BD-NOS participants with sub-threshold episodes and TDCs. N = 175
participants (BD-I = 81, BD-II = 11, BD-NOS = 28, TDC = 55) completed Cambridge
Neuropsychological Automated Testing Battery (CANTAB) tasks. A priori analyses of
the simple reversal stage of the CANTAB intra-/extra-dimensional shift task
showed that aggregated BD-I/II participants required significantly more trials to
complete the task than either BD-NOS participants with sub-syndromal
manic/hypomanic symptoms or than TDCs. BD participants across sub-types had
impairments in sustained attention and information processing for emotionally
valenced words. Our results align with prior findings showing that BD-I/II youths
with distinct episodes have specific alterations in reversal learning. More
broadly, our study suggests that further work is necessary to see the interaction
between neurocognitive performance and longitudinal illness course. Additional
work is required to identify the neural underpinnings of these differences as
targets for potential novel treatments, such as cognitive remediation.
PMID- 26438384
TI - Subretinal heterotopic respiratory epithelium: a case report and literature
review.
AB - A 51-year-old female underwent vitrectomy surgery to remove a group of spherical
subretinal tumors beneath the detached retina. Hematoxylin and eosin staining and
immunohistochemical findings showed that the characteristics of the tumor were
consistent with a subretinal heterotopic respiratory epithelium. This is the
first report of a respiratory epithelial heterotopia located in the subretinal
space.
PMID- 26438385
TI - A proposed clinical and biological interpretation of mediated interaction.
AB - Understanding of causal pathways in epidemiology involves the concepts of direct
and indirect effects. Recently, causal mediation analysis has been formalized to
quantify these direct and indirect effects in the presence of exposure-mediator
interaction and even allows for four-way decomposition of the total effect:
controlled direct effect, reference interaction, mediated interaction, pure
indirect effect. Whereas the other three effects can be intuitively
conceptualized, mediated interaction is often considered a nuisance in
statistical analysis. In this paper, we focus on mediated interaction and
contrast it against pure mediation. We also propose a clinical and biological
interpretation of mediated interaction using three hypothetical examples. With
these examples we aim to make researchers aware that mediated interaction can
actually provide important clinical and biological information.
PMID- 26438386
TI - Levels of interleukin-1 beta can predict response to tocilizumab therapy in
rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab
therapy) study.
AB - Predicting the responses of patients with rheumatoid arthritis (RA) to
tocilizumab is difficult, because inflammatory markers such as C-reactive protein
rapidly normalize regardless of clinical efficacy. We aimed to identify factors
that could predict response to tocilizumab. Sixty-five patients completed 52
weeks of tocilizumab therapy. Serum fibrinogen, D-dimer and interleukin (IL)
1beta levels were measured at baseline and after 4 weeks of therapy. Clinical
responses to tocilizumab were assessed using disease activity score 28
erythrocyte sedimentation rate and the clinical disease activity index at
baseline and after 52 weeks of therapy (UMIN Clinical Trials Registry No.
UMIN000002246). Mean age was 60.5 years (range 22-85 years). Mean disease
duration was 11.2 years (range 0-45 years). All patients had moderate-to-severe
disease activity and were resistant to disease-modifying anti-rheumatic drugs
and/or other biologics. Baseline IL-1beta levels were significantly lower in
responders than in non-responders (p = 0.045), but multiple logistic regression
analysis found no significant difference (adjusted odds ratio 2.74; 95 %
confidence interval 0.84-8.95; p = 0.096). Low D-dimer and IL-1beta levels at 4
weeks predicted greater decrease in disease activity after 52 weeks of treatment
(p = 0.005 and p < 0.001, respectively). Effects of tocilizumab at 52 weeks could
be predicted from D-dimer and IL-1beta levels after 4 weeks of tocilizumab
treatment. These markers might be more useful than current inflammatory markers
for early-stage prediction of response to tocilizumab in RA.
PMID- 26438387
TI - WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density
lipoprotein levels in Tibetan gout patients.
AB - Current evidence suggests heredity and metabolic syndrome contributes to gout
progression. Specifically, the WDR1 and CLNK genes may play a role in gout
progression in European ancestry populations. However, no studies have focused on
Chinese populations, especially Tibetan individuals. This study aims to determine
whether variations in these two genes correlate with gout-related indices in
Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1
and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318
controls. We used one-way analysis of variance to evaluate the polymorphisms'
effects on gout based on mean serum levels of metabolism indicators, such as
albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins
(HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p
values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes
affected multiple risk factors for gout development. Significant differences in
serum GLU levels were detected between different genotypic groups with WDRI
polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition,
significant differences in serum HDL-C levels were detected between different
genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms
of CLNK also affected levels of albumin, triglycerides, and creatinine. This
study is the first to investigate and identify positive correlations between WDR1
and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide
significant evidence for the effect of genetic polymorphisms on gout-related
factors in Chinese-Tibetan populations.
PMID- 26438388
TI - Multidisciplinary dermatology-rheumatology management for patients with moderate
to-severe psoriasis and psoriatic arthritis: a systematic review.
AB - The aim of the study was to analyze the efficacy and satisfaction of
multidisciplinary dermatology-rheumatology management for patients with moderate
to-severe psoriasis and psoriatic arthritis (PsA). We conducted a systematic
literature search in MEDLINE, EMBASE, and Cochrane Library up to September 2015.
Selection criteria include (1) adult patients with moderate-to-severe psoriasis
and PsA, (2) assessed in a multidisciplinary consultation, (3) comparison with
routine separate consultations, and (4) outcome measures to evaluate efficacy
and/or satisfaction. Meta-analyses, systematic reviews, clinical trials, cohort
studies, and case series were included. The quality of the studies included was
graded according to the Oxford Level of Evidence scale. Of 195 articles, three
studies complied with the inclusion criteria: two case series and one descriptive
study in which 506 patients were evaluated. Patients were referred to the
multidisciplinary consultation from dermatology and rheumatology consultations in
all but one study, in which primary care was also involved. The reason for the
referral was to confirm the diagnosis and/or treatment. Patients were evaluated
on a weekly and monthly basis in two and one study, respectively. The evidence
obtained is scarce but suggests the efficacy of multidisciplinary consultations
in terms of improved skin and joint symptoms after changing treatment (82-56 %),
showing higher scores for this type of consultation compared to the usual [4.91
vs. 2.85 (0-5)] and a high level of satisfaction among patients (94 % "very
satisfied"). However, waiting times were higher. With the limited evidence found,
multidisciplinary management seems to be more effective and more satisfactory for
patients with moderate-to-severe psoriasis and PsA than conventional
consultations, though this could not be conclusively demonstrated. The results of
this review support the benefit of implementing this type of consultation.
PMID- 26438389
TI - On the computational implementation of forward and back-projection operations for
cone-beam computed tomography.
AB - Forward- and back-projection operations are the main computational burden in
iterative image reconstruction in computed tomography. In addition, their
implementation has to be accurate to ensure stable convergence to a high-quality
image. This paper reviews and compares some of the variations in the
implementation of these operations in cone-beam computed tomography. We compare
four algorithms for computing the system matrix, including a distance-driven
algorithm, an algorithm based on cubic basis functions, another based on
spherically symmetric basis functions, and a voxel-driven algorithm. The focus of
our study is on understanding how the choice of the implementation of the system
matrix will influence the performance of iterative image reconstruction
algorithms, including such factors as the noise strength and spatial resolution
in the reconstructed image. Our experiments with simulated and real cone-beam
data reveal the significance of the speed-accuracy trade-off in the
implementation of the system matrix. Our results suggest that fast convergence of
iterative image reconstruction methods requires accurate implementation of
forward- and back-projection operations, involving a direct estimation of the
convolution of the footprint of the voxel basis function with the surface of the
detectors. The required accuracy decreases by increasing the resolution of the
projection measurements beyond the resolution of the reconstructed image.
Moreover, reconstruction of low-contrast objects needs more accurate
implementation of these operations. Our results also show that, compared with
regularized reconstruction methods, the behavior of iterative reconstruction
algorithms that do not use a proper regularization is influenced more
significantly by the implementation of the forward- and back-projection
operations.
PMID- 26438390
TI - Hybrid stent device of flow-diverting effect and stent-assisted coil embolization
formed by fractal structure.
AB - This paper presents a novel hybrid medical stent device. This hybrid stent device
formed by fractal mesh structures provides a flow-diverting effect and stent
assisted coil embolization. Flow-diverter stents decrease blood flow into an
aneurysm to prevent its rupture. In general, the mesh size of a flow-diverter
stent needs to be small enough to prevent blood flow into the aneurysm.
Conventional flow-diverter stents are not available for stent-assisted coil
embolization, which is an effective method for aneurysm occlusion, because the
mesh size is too small to insert a micro-catheter for coil embolization. The
proposed hybrid stent device is capable of stent-assisted coil embolization while
simultaneously providing a flow-diverting effect. The fractal stent device is
composed of mesh structures with fine and rough mesh areas. The rough mesh area
can be used to insert a micro-catheter for stent-assisted coil embolization. Flow
diverting effects of two fractal stent designs were composed to three
commercially available stent designs. Flow-diverting effects were analyzed using
computational fluid dynamics (CFD) analysis and particle image velocimetry (PIV)
experiment. Based on the CFD and PIV results, the fractal stent devices reduce
the flow velocity inside an aneurism just as much as the commercially available
flow-diverting stents while allowing stent-assisted coil embolization.
PMID- 26438391
TI - Morphologic variations of lip-print patterns in a Central Indian population: A
preliminary study.
AB - Lip prints can provide vital information that may be useful for the purposes of
forensic investigations. The current study was undertaken with the aims of
determining the distribution and predominant lip-print patterns in a Central
Indian (Marathi) population and evaluating whether any sex differences exist. The
study subjects were 400 healthy consenting volunteers - 200 males and 200 females
- aged 18-25 years, from the Marathi community. A simpler and more convenient
method of data collection - digital photography - was used. The central (most
motile) 1 cm(2) portion of both upper and lower lips was analysed digitally. As
per Suzuki and Tsuchihashi's classification, overall, Type IV (27.5%) and Type
III (6.25%) were found to be the most and least prevalent patterns, respectively.
The Type II (32%) lip-print pattern was found to be most predominant in males,
while Type IV (32.5%) was found to be most commonly occurring in females.
Statistically significant differences (p < .01) were observed between lip-print
pattern types in males and females.
PMID- 26438392
TI - Adult porcine genome-wide DNA methylation patterns support pigs as a biomedical
model.
AB - BACKGROUND: Pigs (Sus scrofa) provide relevant biomedical models to dissect
complex diseases due to their anatomical, genetic, and physiological similarities
with humans. Aberrant DNA methylation has been linked to many of these diseases
and is associated with gene expression; however, the functional similarities and
differences between porcine and human DNA methylation patterns are largely
unknown. METHODS: DNA and RNA was isolated from eight tissue samples (fat, heart,
kidney, liver, lung, lymph node, muscle, and spleen) from the adult female Duroc
utilized for the pig genome sequencing project. Reduced representation bisulfite
sequencing (RRBS) and RNA-seq were performed on an Illumina HiSeq2000. RRBS reads
were aligned using BSseeker2, and only sites with a minimum depth of 10 reads
were used for methylation analysis. RNA-seq reads were aligned using Tophat, and
expression analysis was performed using Cufflinks. In addition, SNP calling was
performed using GATK for targeted control and whole genome sequencing reads for
CpG site validation and allelic expression analysis, respectively. RESULTS:
Analysis on the influence of DNA variation in methylation calling revealed a
reduced effectiveness of WGS datasets in covering CpG rich regions, as well as
the usefulness of a targeted control library for SNP detection. Analysis of over
500,000 CpG sites demonstrated genome wide methylation patterns similar to those
observed in humans, including reduced methylation within CpG islands and at
transcription start sites (TSS), X chromosome inactivation, and anticorrelation
of TSS CpG methylation with gene expression. In addition, a positive correlation
between TSS CpG density and expression, and a negative correlation between TSS
TpG density and expression were demonstrated. Low but non-random non-CpG
methylation (<1%) was also detected in all non-neuronal somatic tissues, with
differences in tissue clustering observed based on CpG and non-CpG methylation
patterns. Finally, allele specific expression analysis revealed enrichment of
genes involved in metabolic and regulatory processes. DISCUSSION: These results
provide transcriptional and DNA methylation datasets for the biomedical community
that are directly relatable to current genomic resources. In addition, the
correlation between TSS CpG density and expression suggests increased mutation
rates at CpG sites play a significant role in adaptive evolution by reducing CpG
density at TSS over time, resulting in higher methylation levels in these regions
and more permanent changes to lower gene expression. This is proposed to occur
predominantly through deamination of 5-methylcytosine to thymidine, resulting in
the replacement of CpG with TpG sites in these regions, as indicated by the
increased TSS TpG density observed in non-expressed genes, resulting in a
negative correlation between expression and TSS TpG density. CONCLUSIONS: This
study provides baseline methylation and gene transcription profiles for a healthy
adult pig, reports similar patterns to those observed in humans, and supports
future porcine studies related to human disease and development. Additionally,
the observed reduced CpG and increased TpG density at TSS of lowly expressed
genes suggests DNA methylation plays a significant role in adaptive evolution
through more permanent changes to lower gene expression.
PMID- 26438393
TI - Temporal transcriptional response to latency reversing agents identifies specific
factors regulating HIV-1 viral transcriptional switch.
AB - BACKGROUND: Latent HIV-1 reservoirs are identified as one of the major challenges
to achieve HIV-1 cure. Currently available strategies are associated with wide
variability in outcomes both in patients and CD4(+) T cell models. This
underlines the critical need to develop innovative strategies to predict and
recognize ways that could result in better reactivation and eventual elimination
of latent HIV-1 reservoirs. RESULTS AND DISCUSSION: In this study, we combined
genome wide transcriptome datasets post activation with Systems Biology approach
(Signaling and Dynamic Regulatory Events Miner, SDREM analyses) to reconstruct a
dynamic signaling and regulatory network involved in reactivation mediated by
specific activators using a latent cell line. This approach identified several
critical regulators for each treatment, which were confirmed in follow-up
validation studies using small molecule inhibitors. Results indicate that
signaling pathways involving JNK and related factors as predicted by SDREM are
essential for virus reactivation by suberoylanilide hydroxamic acid. ERK1/2 and
NF-kappaB pathways have the foremost role in reactivation with prostratin and TNF
alpha, respectively. JAK-STAT pathway has a central role in HIV-1 transcription.
Additional evaluation, using other latent J-Lat cell clones and primary T cell
model, also confirmed that many of the cellular factors associated with latency
reversing agents are similar, though minor differences are identified. JAK-STAT
and NF-kappaB related pathways are critical for reversal of HIV-1 latency in
primary resting T cells. CONCLUSION: These results validate our combinatorial
approach to predict the regulatory cellular factors and pathways responsible for
HIV-1 reactivation in latent HIV-1 harboring cell line models. JAK-STAT have a
role in reversal of latency in all the HIV-1 latency models tested, including
primary CD4(+) T cells, with additional cellular pathways such as NF-kappaB, JNK
and ERK 1/2 that may have complementary role in reversal of HIV-1 latency.
PMID- 26438394
TI - Relationship between myostatin and irisin in type 2 diabetes mellitus: a
compensatory mechanism to an unfavourable metabolic state?
AB - Myostatin and irisin are two myokines related to energy metabolism, acting on
skeletal muscle and recently suggested on adipose tissue in mice. However, the
exact role of these myokines in humans has not been fully established. Our aim
was to evaluate the relationship between serum levels of myostatin and irisin in
type 2 diabetes mellitus patients and non-diabetic controls and to explore its
links with metabolic parameters. Case-control study including 73 type 2 diabetes
mellitus patients and 55 non-diabetic subjects as control group. Circulating
myostatin and irisin levels were measured by enzyme-linked immunosorbent assays.
Type 2 diabetes mellitus patients showed significantly lower myostatin levels (p
= 0.001) and higher irisin levels (p = 0.036) than controls. An inverse
relationship was observed between myostatin and irisin levels (p = 0.002).
Moreover, in type 2 diabetes mellitus patients, after adjusting by confounder
factors, myostatin was negatively related to fasting plasma glucose (p = 0.005)
and to triglyceride levels (p = 0.028) while irisin showed a positive association
with these variables (p = 0.017 and p = 0.006 respectively). A linear regression
analysis showed that irisin and fasting plasma glucose levels were independently
associated to myostatin levels and that myostatin and triglyceride levels were
independently associated to irisin concentrations in type 2 diabetes mellitus
patients. Our results suggest that serum levels of myostatin and irisin are
related in patients with type 2 diabetes. Triglyceride and glucose levels could
modulate myostatin and irisin concentrations as a compensatory mechanism to
improve the metabolic state in these patients although further studies are needed
to elucidate whether the action of these myokines represents an adaptative
response.
PMID- 26438395
TI - The activity of 11beta-hydroxysteroid dehydrogenase type 2 enzyme and cortisol
secretion in patients with adrenal incidentalomas.
AB - In adrenal incidentaloma (AI) patients, beside the cortisol secretion, a
different 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) activity,
measurable by 24-h urinary cortisol/cortisone ratio (R-UFF/UFE) (the higher R
UFF/UFE the lower HSD11B2 activity), could influence the occurrence of the
subclinical hypercortisolism (SH)-related complications (hypertension, type 2
diabetes, obesity). We evaluated whether in AI patients, UFF levels are
associated to UFE levels, and the HSD11B2 activity to the complications presence.
In 156 AI patients (93F, age 65.2 +/- 9.5 years), the following were measured:
serum cortisol after 1 mg-dexamethasone test (1 mg-DST), ACTH, UFF, UFE levels,
and R-UFF/UFE (by liquid chromatography-tandem mass spectrometry), the latter was
also evaluated in 63 matched-controls. We diagnosed SH (n = 22) in the presence
of >=2 among ACTH <2.2 pmol/L, increased UFF levels, and 1 mg-DST >83 nmol/L.
Patients showed higher UFF levels and R-UFF/UFE than controls (75.9 +/- 43.1 vs
54.4 +/- 22.9 nmol/24 h and 0.26 +/- 0.12 vs 0.20 +/- 0.07, p < 0.005,
respectively) but comparable UFE levels (291 +/- 91.1 vs 268 +/- 61.5, p =
0.069). The R-UFF/UFE was higher in patients with high (h-UFF, n = 28, 0.41 +/-
0.20) than in those with normal (n-UFF, 0.22 +/- 0.10, p < 0.005) UFF levels and
in patients with SH than in those without SH (0.30 +/- 0.12 vs 0.25 +/- 0.12, p =
0.04). UFF levels were associated with R-UFF/UFE (r = 0.849, p < 0.001) in n-UFF,
but not in h-UFF patients. Among h-UFF patients, the complications prevalence was
not associated with R-UFF/UFE values. In AI patients, the UFF increase is not
associated with a UFE increase. The HSD11B2 activity is inversely associated with
UFF levels in n-UFF patients but not in h-UFF patients, and it is not associated
with the SH complications.
PMID- 26438396
TI - Increased thyroid cancer incidence in a basaltic volcanic area is associated with
non-anthropogenic pollution and biocontamination.
AB - The increased thyroid cancer incidence in volcanic areas suggests an
environmental effect of volcanic-originated carcinogens. To address this problem,
we evaluated environmental pollution and biocontamination in a volcanic area of
Sicily with increased thyroid cancer incidence. Thyroid cancer epidemiology was
obtained from the Sicilian Regional Registry for Thyroid Cancer. Twenty-seven
trace elements were measured by quadrupole mass spectrometry in the drinking
water and lichens (to characterize environmental pollution) and in the urine of
residents (to identify biocontamination) in the Mt. Etna volcanic area and in
adjacent control areas. Thyroid cancer incidence was 18.5 and 9.6/10(5)
inhabitants in the volcanic and the control areas, respectively. The increase was
exclusively due to the papillary histotype. Compared with control areas, in the
volcanic area many trace elements were increased in both drinking water and
lichens, indicating both water and atmospheric pollution. Differences were
greater for water. Additionally, in the urine of the residents of the volcanic
area, the average levels of many trace elements were significantly increased,
with values higher two-fold or more than in residents of the control area:
cadmium (*2.1), mercury (*2.6), manganese (*3.0), palladium (*9.0), thallium
(*2.0), uranium (*2.0), vanadium (*8.0), and tungsten (*2.4). Urine
concentrations were significantly correlated with values in water but not in
lichens. Our findings reveal a complex non-anthropogenic biocontamination with
many trace elements in residents of an active volcanic area where thyroid cancer
incidence is increased. The possible carcinogenic effect of these chemicals on
the thyroid and other tissues cannot be excluded and should be investigated.
PMID- 26438397
TI - Statin reduces orbitopathy risk in patients with Graves' disease by modulating
apoptosis and autophagy activities.
AB - Statins use has been associated with reduced risk for developing orbitopathy
among patients with Graves' disease. We hypothesize that statin reduces
orbitopathy risk mainly by modulating both apoptosis and autophagy activities in
patients with Graves' disease.
PMID- 26438398
TI - "You cannot eat rights": a qualitative study of views by Zambian HIV-vulnerable
women, youth and MSM on human rights as public health tools.
AB - BACKGROUND: Human rights approaches now dominate the HIV prevention landscape
across sub-Saharan Africa, yet little is known about how they are viewed by the
populations they are designed to serve. Health interventions are most effective
when they resonate with the worldviews and interests of target groups. This study
examined local Zambian understandings of human rights approaches to HIV
prevention among three highly HIV-vulnerable groups: women, youth, and men-who
have-sex-with-men (MSM). METHODS: Focus groups included 23 women, youth, and MSM
who had participated in activities organized by local non-governmental
organizations (NGOs) using rights-based approaches, and interviews included 10
Zambian employees of these NGOs. Topics included participants' experiences and
views of the utility of these activities. Thematic analysis mapped out diverse
ways participants viewed the concept of human rights in relation to HIV
prevention. RESULTS: Whilst NGO workers noted the need for human rights programs
to address the complex drivers of the HIV epidemic, they struggled to tailor them
to the Zambian context due to donor stipulations. Women program beneficiaries
noted that the concept of human rights helped challenge harmful sexual practices
and domestic abuse, and youth described rights-based approaches as more
participatory than previous HIV-prevention efforts. However, they criticized the
approach for conflicting with traditional values such as respect for elders and
'harmonious' marital relationships. They also critiqued it for threatening the
social structures and relationships that they relied on for material survival,
and for failing to address issues like poverty and unemployment. In contrast, MSM
embraced the rights approach, despite being critical of its overly
confrontational implementation. CONCLUSIONS: A rights-based approach seeks to
tackle the symbolic drivers of HIV-its undeniable roots in cultural and religious
systems of discrimination. Yet, it fails to resonate with youth and women's own
understandings of their needs and priorities due to its neglect of material
drivers of HIV such as poverty and unemployment. MSM, who suffer extreme stigma
and discrimination, have less to lose and much to gain from an approach that
challenges inequitable social systems. Developing effective HIV-prevention
strategies requires careful dialogue with vulnerable groups and greater
flexibility for context-specific implementation rather than a one-size-fits-all
conceptualization of human rights.
PMID- 26438399
TI - Multiple sclerosis: relapses, resource use, and costs.
AB - BACKGROUND: Relapses can have a major impact on the lives of people with multiple
sclerosis (MS), and yet relapse-related healthcare costs have received little
attention. This has limited cost-effectiveness analyses of treatments for MS and
hampered decision-making regarding the funding of MS healthcare services.
OBJECTIVE: To describe health/social care resource use and costs according to the
frequency, severity, and endurance of MS relapses. METHODS: Data from the
prospective, longitudinal UK South West Impact of Multiple Sclerosis cohort were
used. A total of 11,800 questionnaires from 1441 people with MS were available,
including data on relapses, contacts with health/social care professionals, and
other MS-related resource use. RESULTS: The mean (SD) 6-monthly MS-related
health/social care cost for individuals who reported a relapse was L519 (L949),
compared to L229 (L366) for those who had not did report a relapse. Care costs
varied widely dependent on the characteristics of the relapse. The mean (SD) cost
when a relapse was not treated with steroids was L381 (L780), whilst the
equivalent cost was L3579 (L1727) when a relapse resulted in hospitalization.
CONCLUSIONS: The impact of relapses on health and social care resources and costs
differs according to their frequency, length, and severity. The data provided
here can be used in cost-effectiveness analyses and to inform decision-making
regarding healthcare provision for people with this condition.
PMID- 26438401
TI - Blockade of KCa3.1 potassium channels protects against cisplatin-induced acute
kidney injury.
AB - Tubular cell apoptosis significantly contributes to cisplatin-induced acute
kidney injury (AKI) pathogenesis. Although KCa3.1, a calcium-activated potassium
channel, participates in apoptosis, its involvement in cisplatin-induced AKI is
unknown. Here, we found that cisplatin treatment triggered an early induction of
KCa3.1 expression associated with HK-2 cell apoptosis, the development of renal
tubular damage, and apoptosis in mice. Treatment with the highly selective KCa3.1
blocker TRAM-34 suppressed cisplatin-induced HK-2 cell apoptosis. We further
assessed whether KCa3.1 mediated cisplatin-induced AKI in genetic knockout and
pharmacological blockade mouse models. KCa3.1 deficiency reduced renal function
loss, renal tubular damage, and the induction of the apoptotic marker caspase-3
in the kidneys of cisplatin-treated KCa3.1 (-/-) mice. Pharmacological blockade
of KCa3.1 by TRAM-34 similarly attenuated cisplatin-induced AKI in mice.
Furthermore, we dissected the mechanisms underlying cisplatin-induced apoptosis
reduction via KCa3.1 blockade. We found that KCa3.1 blockade attenuated
cytochrome c release and the increase in the intrinsic apoptotic mediators Bax,
Bak, and caspase-9 after cisplatin treatment. KCa3.1 blocking inhibited the
cisplatin-induced activation of the endoplasmic reticulum (ER) stress mediator
caspase-12, which is independent of calcium-dependent protease m-calpain
activation. Taken together, KCa3.1 blockade protects against cisplatin-induced
AKI through the attenuation of apoptosis by interference with intrinsic apoptotic
and ER stress-related mediators, providing a potential target for the prevention
of cisplatin-induced AKI.
PMID- 26438402
TI - Oxidative DNA damage enhances the carcinogenic potential of in vitro chronic
arsenic exposures.
AB - Chronic exposure to arsenic is known to increase the incidence of cancer in
humans. Our previous work demonstrated that environmentally relevant arsenic
exposures generate an accelerated accumulation of pre-carcinogen 8-OH-dG DNA
lesions under Ogg1-deficient backgrounds, but it remains unproved whether this
observed arsenic-induced oxidative DNA damage (ODD) is certainly important in
terms of cancer. Here, isogenic MEF Ogg1 (+/+) cells and MEF Ogg1 (-/-) cells
unable to properly eliminate 8-OH-dG from DNA-were exposed to 0.5, 1 and 2 uM of
sodium arsenite for 40 weeks. The acquisition of an in vitro cancer-like
phenotype was assessed throughout the exposure; matrix metalloproteinase (MMP)
activities were measured by zymography, colony formation and promotion were
evaluated by soft agar assay, and cellular invasiveness was measured by the
transwell assay. Alterations in cellular morphology, growth and differentiation
status were also included as complementary measures of transformation. MEF Ogg1 (
/-) cells showed a cancer-associated phenotype after 30 weeks of exposure, as
indicated by morphological changes, increased proliferation, deregulated
differentiation status, increased MMPs secretion, anchorage-independent cell
growth and enhancement of tumor growth and invasiveness. Conversely, MEF Ogg1
(+/+) cells did not present changes in morphology or proliferation, exhibited a
milder degree of gene deregulation and needed 10 weeks of additional exposure to
the highest arsenite doses to show tumor enhancing effects. Thus, Ogg1 genetic
background and arsenic-induced 8-OH-dG proved relevant for arsenic-mediated
carcinogenic effects. To our knowledge, this is the first study directly linking
ODD with arsenic carcinogenesis.
PMID- 26438403
TI - Boxplots for grouped and clustered data in toxicology.
AB - The vast majority of toxicological papers summarize experimental data as bar
charts of means with error bars. While these graphics are easy to generate, they
often obscure essential features of the data, such as outliers or subgroups of
individuals reacting differently to a treatment. In particular, raw values are of
prime importance in toxicology; therefore, we argue they should not be hidden in
messy supplementary tables but rather unveiled in neat graphics in the results
section. We propose jittered boxplots as a very compact yet comprehensive and
intuitively accessible way of visualizing grouped and clustered data from
toxicological studies together with individual raw values and indications of
statistical significance. A web application to create these plots is available
online.
PMID- 26438400
TI - Inflammation-associated extracellular beta-glucuronidase alters cellular
responses to the chemical carcinogen benzo[a]pyrene.
AB - Neutrophils infiltrate tissues during inflammation, and when activated, they
release beta-glucuronidase. Since inflammation is associated with carcinogenesis,
we investigated how extracellular beta-glucuronidase changed the in vitro
cellular response to the chemical carcinogen benzo(a)pyrene (B[a]P). For this we
exposed human liver (HepG2) and lung (A549) cells to B[a]P in the presence or
absence of beta-glucuronidase. beta-Glucuronidase reduced B[a]P-induced
expression of CYP1A1 and CYP1B1 at 6 h after exposure, which did not depend on
beta-glucuronidase activity, because the inhibitor D-saccharic acid 1,4-lactone
monohydrate did not antagonize the effect of beta-glucuronidase. On the other
hand, the inhibitory effect of beta-glucuronidase on CYP expression was dependent
on signalling via the insulin-like growth factor receptor (IGF2R, a known
receptor for beta-glucuronidase), because co-incubation with the IGF2R inhibitor
mannose-6-phosphate completely abolished the effect of beta-glucuronidase.
Extracellular beta-glucuronidase also reduced the formation of several B[a]P
metabolites and B[a]P-DNA adducts. Interestingly, at 24 h of exposure, beta
glucuronidase significantly enhanced CYP expression, probably because beta
glucuronidase de-glucuronidated B[a]P metabolites, which continued to trigger the
aryl hydrocarbon receptor (Ah receptor) and induced expression of CYP1A1 (in both
cell lines) and CYP1B1 (in A549 only). Consequently, significantly higher
concentrations of B[a]P metabolites and DNA adducts were found in beta
glucuronidase-treated cells at 24 h. DNA adduct levels peaked at 48 h in cells
that were exposed to B[a]P and treated with beta-glucuronidase. Overall, these
data show that beta-glucuronidase alters the cellular response to B[a]P and
ultimately enhances B[a]P-induced DNA adduct levels.
PMID- 26438404
TI - Effects of copper toxicity on response inhibition processes: a study in Wilson's
disease.
AB - Wilson's disease (WD) is a rare genetic disease causing copper deposits in
various tissues. Given the specificity of the underlying pathology, it is a good
model to investigate the effects of copper toxicity on cognitive functions in
humans. If left untreated, WD results in neurodegeneration and organ failure, but
irrespective of potential brain damage, the medication might reduce cortical
norepinephrine (NE) levels. In line with this, dysexecutive symptoms including
increased impulsivity have been reported for WD patients, but the underlying
mechanisms have remained elusive. We investigated inhibition and the associated
neurophysiological correlates in n = 26 WD patients with mild-to-moderate
clinical symptoms and matched healthy controls who completed a Go/Nogo task,
while an EEG was recorded. Although the behavioral data do not show increased
impulsivity in WD, the neurophysiological data show that evaluative processing of
successful inhibition (as reflected by the P3 component) was strongly
compromised. This was reflected by a decrease in ACC activity which was
positively correlated with the severity of WD symptoms, stressing the importance
of copper (toxicity) for neurocognitive functioning and impulsivity. These
changes are most likely due to a combination of NE deficiency induced by WD
medication as well as WD-induced brain damage. The fact that changes were still
evident on a neurophysiological level suggests that neurophysiological correlates
of cognitive processes and functions provide a more sensitive index of toxicity
and/or treatment efficiency than purely behavioral measures.
PMID- 26438405
TI - Optimality in the zonation of ammonia detoxification in rodent liver.
AB - The rodent liver eliminates toxic ammonia. In mammals, three enzymes (or enzyme
systems) are involved in this process: glutaminase, glutamine synthetase and the
urea cycle enzymes, represented by carbamoyl phosphate synthetase. The
distribution of these enzymes for optimal ammonia detoxification was determined
by numerical optimization. This in silico approach predicted that the enzymes
have to be zonated in order to achieve maximal removal of toxic ammonia and
minimal changes in glutamine concentration. Using 13 compartments, representing
hepatocytes, the following predictions were generated: glutamine synthetase is
active only within a narrow pericentral zone. Glutaminase and carbamoyl phosphate
synthetase are located in the periportal zone in a non-homogeneous distribution.
This correlates well with the paradoxical observation that in a first step
glutamine-bound ammonia is released (by glutaminase) although one of the
functions of the liver is detoxification by ammonia fixation. The in silico
approach correctly predicted the in vivo enzyme distributions also for non
physiological conditions (e.g. starvation) and during regeneration after
tetrachloromethane (CCl4) intoxication. Metabolite concentrations of glutamine,
ammonia and urea in each compartment, representing individual hepatocytes, were
predicted. Finally, a sensitivity analysis showed a striking robustness of the
results. These bioinformatics predictions were validated experimentally by
immunohistochemistry and are supported by the literature. In summary,
optimization approaches like the one applied can provide valuable explanations
and high-quality predictions for in vivo enzyme and metabolite distributions in
tissues and can reveal unknown metabolic functions.
PMID- 26438406
TI - Infarction of the lingula following left upper lobe trisegmentectomy.
AB - Anatomical segmentectomy has emerged as the procedure of choice for early-stage
non-small-cell lung cancer, especially in the presence of poor cardiopulmonary
reserve. The most common postoperative complications are pneumonia, persistent
air leak, and rarely, vascular compromise of the remaining lobe. We report the
case of a 74-year-old woman who underwent thoracotomy and left upper lobe
trisegmentectomy for T1bN0Mo squamous cell carcinoma and subsequently developed
infarction and hepatization of the remaining lingula. A completion left upper
lobectomy was performed and the patient made a full recovery.
PMID- 26438407
TI - Hypertension in pregnancy: An unresectable mediastinal pheochromocytoma.
AB - Hypertension is a relatively common occurrence during pregnancy, which usually
has a benign course with an excellent prognosis. However, physicians caring for
pregnant women should have a high index of suspicion for underlying medical
conditions that could lead to a more perilous outcome. Herein, we present the
case of a pregnant woman who was found to have uncontrollable hypertension late
in her pregnancy, secondary to a mediastinal pheochromocytoma, which was deemed
unresectable at the time of exploration after her delivery.
PMID- 26438408
TI - Combined 3D-QSAR, molecular docking, and molecular dynamics study of tacrine
derivatives as potential acetylcholinesterase (AChE) inhibitors of Alzheimer's
disease.
AB - Acetylcholinesterase (AChE) is one of the key targets of drugs for treating
Alzheimer's disease (AD). Tacrine is an approved drug with AChE-inhibitory
activity. In this paper, 3D-QSAR, molecular docking, and molecular dynamics were
carried out in order to study 60 tacrine derivatives and their AChE-inhibitory
activities. 3D-QSAR modeling resulted in an optimal CoMFA model with q(2) = 0.552
and r(2) = 0.983 and an optimal CoMSIA model with q(2) = 0.581 and r(2) = 0.989.
These QSAR models also showed that the steric and H-bond fields of these
compounds are important influences on their activities. The interactions between
these inhibitors and AChE were further explored through molecular docking and
molecular dynamics simulation. A few key residues (Tyr70, Trp84, Tyr121, Trp279,
and Phe330) at the binding site of AChE were identified. The results of this
study improve our understanding of the mechanisms of AChE inhibitors and afford
valuable information that should aid the design of novel potential AChE
inhibitors. Graphical Abstract Superposition of backbone atoms of the lowest
energy structure obtained from MD simulation (magenta) onto those of the
structure of the initial molecular docking model (green).
PMID- 26438409
TI - Specific Diversity of Metarhizium Isolates Infecting Aeneolamia spp. (Hemiptera:
Cercopidae) in Sugarcane Plantations.
AB - Spittlebugs from the genus Aeneolamia are important pests of sugarcane. Although
the use of the entomopathogenic fungus Metarhizum anisopliae s.l. for control of
this pest is becoming more common in Mexico, fundamental information regarding M.
anisopliae in sugarcane plantations is practically non-existent. Using
phylogenetic analysis, we determined the specific diversity of Metarhizium spp.
infecting adult spittlebugs in sugarcane plantations from four Mexican states. We
obtained 29 isolates of M. anisopliae s.str. Haplotype network analysis revealed
the existence of eight haplotypes. Eight selected isolates, representing the four
Mexican states, were grown at different temperatures in vitro; isolates from
Oaxaca achieved the greatest growth followed by isolates from Veracruz, San Luis
Potosi and Tabasco. No relationship was found between in vitro growth and
haplotype diversity. Our results represent a significant contribution to the
better understanding of the ecology of Metarhizum spp. in the sugarcane
agroecosystem.
PMID- 26438410
TI - Pharyngo-jugular fistula after "salvage" total laryngectomy: a case report.
AB - INTRODUCTION: We present a rare case of pharyngo-jugular fistula in a patient who
underwent salvage total laryngectomy after organ-sparing radiochemotherapy. CASE
PRESENTATION: A 77-year-old Caucasian man underwent total laryngectomy and
bilateral neck dissection as salvage surgery after the failure of
radiochemotherapy at another hospital. Thirty-five days after surgery, he was
admitted to our emergency room for fever and massive oral bleeding during meals.
Videopanendoscopy showed the presence of a large clot at the base of his tongue,
while a neck computed tomography scan showed a pharyngo-jugular fistula with the
presence of air in the left internal jugular vein. Cervicotomy was performed: the
internal jugular vein was ligated and sectioned, and the pharyngeal defect was
repaired with a pectoralis major myocutaneous flap. The postoperative period was
uneventful. Twenty-five days post surgery, videofluorography showed the fistula
had disappeared. Our patient then began oral feeding without complications and
was discharged. At present, 5 years after the operation, our patient is alive and
shows no evidence of disease. CONCLUSIONS: Pharyngo-jugular fistula is an
uncommon complication after total laryngectomy, especially in the chemoradiation
era, which is potentially fatal if not promptly treated.
PMID- 26438411
TI - Plant species introduced by foreigners according to folk tradition in Norway and
some other European countries: xenophobic tales or not?
AB - BACKGROUND: In their quest to understand and interpret nature, people have
frequently sought religious or divine origins for plant species and their
characteristics. Less often, historical events or persons are involved. This
study comprises eleven cases of the latter kind, all claiming that plant species
have been introduced by foreigners or at least from foreign lands. METHODS: Based
on literature data and a few cases recorded during my own ethnobotanical field
work, eleven European examples of pseudo-historical plant origins are presented
here, including Cakile maritima, Cicuta virosa, Lathyrus japonicus, Leymus
arenarius, Primula vulgaris, and Scopolia carniolica in Norway, Heracleum
mantegazzianum and/or H. persicum in Denmark, Phoenix dactylifera and P.
theophrastii in Greece, and Jacobaea vulgaris in Scotland. RESULTS: The only
common trait in these stories is that foreigner or at least foreign lands are
claimed as sources of the plant species. In most cases, the "historical"
explanations given in folk tradition are demonstrably at odds with reality. In
those cases that involve poisonous or potentially harmful species (Cicuta virosa,
Heracleum mantegazzianum and/or H. persicum, Jacobaea vulgaris), or the "useless"
Phoenix theophrastii, with its inedible fruits, the stories may be interpreted as
xenophobic, blaming foreigners for introducing dangerous or worthless species.
The remaining examples merely suggest a search for exotic and seemingly rational,
if erroneous, origins for plant species and stands that people considered strange
and unusual. CONCLUSION: The spreading vectors assumed in folk tradition are
correct and well documented, e.g. ship cargos (including goods and packing
materials), which are responsible for introducing ballast plants and other
anthropochores, and wartime activities, introducing a broad range of species
(polemochores). They do not, however, apply to the species included in this
study, which are either indigenous plants or introduced ornamentals. The
foreigners appearing in the folk tales serve mostly as suitably exotic
explanations for what is perceived "alien" plants.
PMID- 26438412
TI - Plant resistance against the parasitic nematode Heterodera schachtii is mediated
by MPK3 and MPK6 kinases, which are controlled by the MAPK phosphatase AP2C1 in
Arabidopsis.
AB - Plant-parasitic cyst nematodes infect plants and form highly sophisticated
feeding sites in roots. It is not known which plant cell signalling mechanisms
trigger plant defence during the early stages of nematode parasitism. Mitogen
activated protein kinases (MAPKs) are central components of protein
phosphorylation cascades transducing extracellular signals to plant defence
responses. MAPK phosphatases control kinase activities and the signalling
outcome. The involvement and the role of MPK3 and MPK6, as well as the MAPK
phosphatase AP2C1, is demonstrated during parasitism of the beet cyst nematode
Heterodera schachtii in Arabidopsis. Our data reveal notable activation patterns
of plant MAPKs and the induction of AP2C1 suggesting the attenuation of defence
signalling in plant cells during early nematode infection. It is demonstrated
that the ap2c1 mutant that is lacking AP2C1 is more attractive but less
susceptible to nematodes compared with the AP2C1-overexpressing line. This
implies that the function of AP2C1 is a negative regulator of nematode-induced
defence. By contrast, the enhanced susceptibility of mpk3 and mpk6 plants
indicates a positive role of stress-activated MAPKs in plant immunity against
nematodes. Evidence is provided that phosphatase AP2C1, as well as AP2C1-targeted
MPK3 and MPK6, are important regulators of plant-nematode interaction, where the
co-ordinated action of these signalling components ensures the timely activation
of plant defence.
PMID- 26438413
TI - Transgenic rice seed expressing flavonoid biosynthetic genes accumulate
glycosylated and/or acylated flavonoids in protein bodies.
AB - Plant-specialized (or secondary) metabolites represent an important source of
high-value chemicals. In order to generate a new production platform for these
metabolites, an attempt was made to produce flavonoids in rice seeds. Metabolome
analysis of these transgenic rice seeds using liquid chromatography-photodiode
array-quadrupole time-of-flight mass spectrometry was performed. A total of 4392
peaks were detected in both transgenic and non-transgenic rice, 20-40% of which
were only detected in transgenic rice. Among these, 82 flavonoids, including 37
flavonols, 11 isoflavones, and 34 flavones, were chemically assigned. Most of the
flavonols and isoflavones were O-glycosylated, while many flavones were O
glycosylated and/or C-glycosylated. Several flavonoids were acylated with
malonyl, feruloyl, acetyl, and coumaroyl groups. These glycosylated/acylated
flavonoids are thought to have been biosynthesized by endogenous rice enzymes
using newly synthesized flavonoids whose biosynthesis was catalysed by exogenous
enzymes. The subcellular localization of the flavonoids differed depending on the
class of aglycone and the glycosylation/acylation pattern. Therefore, flavonoids
with the intended aglycones were efficiently produced in rice seeds via the
exogenous enzymes introduced, while the flavonoids were variously
glycosylated/acylated by endogenous enzymes. The results suggest that rice seeds
are useful not only as a production platform for plant-specialized metabolites
such as flavonoids but also as a tool for expanding the diversity of flavonoid
structures, providing novel, physiologically active substances.
PMID- 26438414
TI - Impact of endobronchial coiling on segmental bronchial lumen in treated and
untreated lung lobes: Correlation with changes in lung volume, clinical and
pulmonary function tests.
AB - OBJECTIVES: To assess the impact of endobronchial coiling on the segment bronchus
cross-sectional area and volumes in patients with lung emphysema using
quantitative chest-CT measurements. MATERIALS AND METHODS: Thirty patients
(female = 15; median age = 65.36 years) received chest-CT before and after
endobronchial coiling for lung volume reduction (LVR) between January 2010 and
December 2014. Thin-slice (0.6 mm) non-enhanced image data sets were acquired
both at end-inspiration and end-expiration using helical technique and 120 kV/100
150 mAs. Clinical response was defined as an increase in the walking distance
(Six-minute walk test; 6MWT) after LVR-therapy. Additionally, pulmonary function
test (PFT) measurements were used for clinical correlation. RESULTS: In the
treated segmental bronchia, the cross-sectional lumen area showed significant
reduction (p < 0.05) in inspiration and tendency towards enlargement in
expiration (p > 0.05). In the ipsilateral lobes, the lumina showed no significant
changes. In the contralateral lung, we found tendency towards increased cross
sectional area in inspiration (p = 0.06). Volumes of the treated segments
correlated with the treated segmental bronchial lumina in expiration (r = 0.80, p
< 0.001). Clinical correlation with changes in 6MWT/PFT showed a significant
decrease of the inspiratory volume of the treated lobe in responders only.
CONCLUSION: Endobronchial coiling causes significant decrease in the cross
sectional area of treated segment bronchi in inspiration and a slight increase in
expiration accompanied by a volume reduction. KEY POINTS: * Endobronchial coiling
has indirect impact on cross-sectional area of treated segment bronchi * Volume
changes of treated lobes correlate with changes in bronchial cross-sectional area
* Coil-induced effects reflect their stabilizing and stiffening impact on lung
parenchyma * Endobronchial coiling reduces bronchial collapsing compensating the
loss of elasticity.
PMID- 26438415
TI - The Predictive Syndemic Effect of Multiple Psychosocial Problems on Health Care
Costs and Utilization among Sexual Minority Women.
AB - Previous studies documenting sexual minority women's disproportionate risk for a
range of medical, mental health, and substance use disorders have not provided a
predictive framework for understanding their interrelations and outcomes. The
present study aimed to address this gap by testing the syndemic effect of co
occurring psychosocial problems on 7-year health care costs and utilization among
sexual minority women. The sample was comprised of sexual minority women (N =
341) who were seen at an urban LGBT-affirmative community health center. Medical
and mental health care utilization and cost data were extracted from electronic
medical records. Demographically adjusted regression models revealed that co
occurring psychosocial problems (i.e., childhood sexual abuse, partner violence,
substance use, and mental health distress [history of suicide attempt]) were all
strongly interrelated. The presence of these indicators had a syndemic (additive)
effect on medical costs and utilization and mental health utilization over 7-year
follow-up, but no effect on 7-year mental health costs. These results suggest
that the presence and additive effect of these syndemic conditions may, in part,
explain increased medical costs and utilization (and higher medical morbidity)
among sexual minority women.
PMID- 26438417
TI - Acute Respiratory Distress Syndrome: Mortality in a Single Center According to
Different Definitions.
AB - BACKGROUND: Mortality in acute lung injury (ALI) remains high, with outcome data
arising mostly from multicenter studies. We undertook this investigation to
determine hospital mortality in patients with ALI in a single center. METHODS: We
studied patients admitted between 2005 and 2012 with ALI and acute respiratory
distress syndrome (ARDS) according to the American European Consensus Conference
(AECC) criteria and recorded clinical variables. Thereafter, patients were
classified as subgroups according to the AECC and Berlin definition in order to
compare the clinical characteristics and outcomes. RESULTS: In the 93 patients
comprising the study, hospital mortality was 38%. Mortality at 28 days was 36%.
Multivariate analysis associated hospital mortality with age and Pao2/Fio2 on day
1 ( P < .001). Differences resulted between the subgroups of AECC (ALI vs ARDS)
and Berlin (mild vs moderate vs severe ARDS) in the lung injury score, Pao2/Fio2,
Pao2/PAo2, PaCo2 on day 1, and hospital mortality. CONCLUSION: The overall
hospital mortality (38%) was similar to that of other studies and according to
the presence of ARDS (Pao2/Fio2 <= 200), we found significant differences between
ALI and ARDS (AECC) and between mild and moderate or severe ARDS (Berlin) in
baseline respiratory variables and mortality.
PMID- 26438416
TI - Substantial genome synteny preservation among woody angiosperm species:
comparative genomics of Chinese chestnut (Castanea mollissima) and plant
reference genomes.
AB - BACKGROUND: Chinese chestnut (Castanea mollissima) has emerged as a model species
for the Fagaceae family with extensive genomic resources including a physical
map, a dense genetic map and quantitative trait loci (QTLs) for chestnut blight
resistance. These resources enable comparative genomics analyses relative to
model plants. We assessed the degree of conservation between the chestnut genome
and other well annotated and assembled plant genomic sequences, focusing on the
QTL regions of most interest to the chestnut breeding community. RESULTS: The
integrated physical and genetic map of Chinese chestnut has been improved to now
include 858 shared sequence-based markers. The utility of the integrated map has
also been improved through the addition of 42,970 BAC (bacterial artificial
chromosome) end sequences spanning over 26 million bases of the estimated 800 Mb
chestnut genome. Synteny between chestnut and ten model plant species was
conducted on a macro-syntenic scale using sequences from both individual probes
and BAC end sequences across the chestnut physical map. Blocks of synteny with
chestnut were found in all ten reference species, with the percent of the
chestnut physical map that could be aligned ranging from 10 to 39 %. The
integrated genetic and physical map was utilized to identify BACs that spanned
the three previously identified QTL regions conferring blight resistance. The
clones were pooled and sequenced, yielding 396 sequence scaffolds covering 13.9
Mbp. Comparative genomic analysis on a microsytenic scale, using the QTL
associated genomic sequence, identified synteny from chestnut to other plant
genomes ranging from 5.4 to 12.9 % of the genome sequences aligning. CONCLUSIONS:
On both the macro- and micro-synteny levels, the peach, grape and poplar genomes
were found to be the most structurally conserved with chestnut. Interestingly,
these results did not strictly follow the expectation that decreased phylogenetic
distance would correspond to increased levels of genome preservation, but rather
suggest the additional influence of life-history traits on preservation of
synteny. The regions of synteny that were detected provide an important tool for
defining and cataloging genes in the QTL regions for advancing chestnut blight
resistance research.
PMID- 26438418
TI - Discretization of gene expression data revised.
AB - Gene expression measurements represent the most important source of biological
data used to unveil the interaction and functionality of genes. In this regard,
several data mining and machine learning algorithms have been proposed that
require, in a number of cases, some kind of data discretization to perform the
inference. Selection of an appropriate discretization process has a major impact
on the design and outcome of the inference algorithms, as there are a number of
relevant issues that need to be considered. This study presents a revision of the
current state-of-the-art discretization techniques, together with the key
subjects that need to be considered when designing or selecting a discretization
approach for gene expression data.
PMID- 26438419
TI - Computational modelling of atherosclerosis.
AB - Atherosclerosis is one of the principle pathologies of cardiovascular disease
with blood cholesterol a significant risk factor. The World Health Organization
estimates that approximately 2.5 million deaths occur annually because of the
risk from elevated cholesterol, with 39% of adults worldwide at future risk.
Atherosclerosis emerges from the combination of many dynamical factors, including
haemodynamics, endothelial damage, innate immunity and sterol biochemistry.
Despite its significance to public health, the dynamics that drive
atherosclerosis remain poorly understood. As a disease that depends on multiple
factors operating on different length scales, the natural framework to apply to
atherosclerosis is mathematical and computational modelling. A computational
model provides an integrated description of the disease and serves as an in
silico experimental system from which we can learn about the disease and develop
therapeutic hypotheses. Although the work completed in this area to date has been
limited, there are clear signs that interest is growing and that a nascent field
is establishing itself. This article discusses the current state of modelling in
this area, bringing together many recent results for the first time. We review
the work that has been done, discuss its scope and highlight the gaps in our
understanding that could yield future opportunities.
PMID- 26438420
TI - Vitamin D deficiency versus non-accidental trauma: comment on "Rickets or abuse?
A histologic comparison of rickets and child abuse-related fractures".
PMID- 26438421
TI - Drawing the line.
AB - The pea aphid Acyrthosiphon pisum is an agriculturally important pest of
leguminous plants including peas and broad beans. The widespread use of chemical
pesticides impacts heavily on the environment, and increases pesticide-resistant
pea aphid populations, so alternative strategies are being actively sought.
Pseudomonas syringae bacteria are known to infect and kill the pea aphid, and
offer a possible control strategy. In this study, the authors measured the
effects of injecting P. syringae on the survival of pea aphid populations at 24
and 48 hours. The pea aphid population was killed more rapidly (98 % after 24
hours) with a higher concentration of injected bacteria than in the control or
with lower concentrations, indicating that a P. syringae-based control strategy
may be a useful alternative to conventional pesticides.
PMID- 26438422
TI - Glycoside hydrolase family 32 is present in Bacillus subtilis phages.
AB - BACKGROUND: Glycoside hydrolase family 32 (GH32) enzymes cleave the glycosidic
bond between two monosaccharides or between a carbohydrate and an aglycone
moiety. GH32 enzymes have been studied in prokaryotes and in eukaryotes but not
in viruses. FINDINGS: This is the first analysis of GH32 enzymes in Bacillus
subtilis phage SP10, phiNIT1 and SPG24. Phylogenetic analysis, molecular docking
and secretability predictions suggest that phage GH32 enzymes function as levan
(fructose homopolysaccharide) fructotransferase. CONCLUSIONS: We showed that
viruses also contain GH32 enzymes and that our analyses in silico strongly
suggest that these enzymes function as levan fructotransferase.
PMID- 26438423
TI - Mobile Image Interpretation: Diagnostic Performance of CT Exams Displayed on a
Tablet Computer in Detecting Abdominopelvic Hemorrhage.
AB - To investigate whether abdominopelvic hemorrhage shown on computed tomography
(CT) images can be diagnosed with the same accuracy on a tablet computer as on a
dedicated reading display. One hundred patients with a clinical suspicion of
abdominopelvic hemorrhage that underwent biphasic CT imaging were retrospectively
read by two readers on a dedicated reading display (reference standard) and on a
tablet computer (iPad Air). Reading was performed in a dedicated reading room
with ambient light conditions. Image evaluation included signs of an active
hemorrhage (extravasation of contrast media) and different signs indicating a
condition after abdominopelvic hemorrhage (hematoma, intestinal clots, vessel
stump, free abdominopelvic fluid with a mean Hounsfield unit value >20, and
asymmetric muscle volume indicating intramuscular hemorrhage). Sensitivity,
specificity, and positive and negative predictive values (PPV/NPV) were
calculated for the tablet-based reading. Active abdominopelvic hemorrhage (n =
72) was diagnosed with the tablet computer with a sensitivity of 0.96, a
specificity of 0.93, a PPV of 0.97, and an NPV of 0.90. The results for the
detection of the signs indicating a condition after abdominopelvic hemorrhage
range from 0.83 to 1.00 in the case of sensitivity, from 0.95 to 1.00 in the case
of specificity, from 0.94 to 1.00 in the case of the PPV, and from 0.96 to 1.00
in the case of the NPV. Abdominopelvic hemorrhage shown on CT images can be
diagnosed on a tablet computer with a high diagnostic accuracy allowing mobile on
call diagnoses. This may be helpful because an early and reliable diagnosis at
any time is crucial for an adequate treatment strategy.
PMID- 26438424
TI - An Evaluation of Performance Characteristics of Primary Display Devices.
AB - The aim of this study was to complete a full evaluation of the new EIZO RX850
liquid crystal display and compare it to two currently used medical displays in
Australia (EIZO GS510 and Barco MDCG 5121). The American Association of
Physicists in Medicine (AAPM) Task Group 18 Quality Control test pattern was used
to assess the performance of three high-resolution primary medical displays: EIZO
RX850, EIZO GS510, and Barco MDCG 5121. A Konica Minolta spectroradiometer (CS
2000) was used to assess luminance response, non-uniformity, veiling glare, and
color uniformity. Qualitative evaluation of noise was also performed. Seven
breast lesions were displayed on each monitor and photographed with a calibrated
5.5-MP Olympus E-1 digital SLR camera. ImageJ software was used to sample pixel
information from each lesion and surrounding background to calculate their
conspicuity index on each of the displays. All monitor fulfilled all AAPM
acceptance criteria. The performance characteristics for EIZO RX850, Barco MDCG
5121, and EIZO GS510 respectively were as follows: maximum luminance (490, 500.5,
and 413 cd/m(2)), minimum luminance (0.724, 1.170, and 0.92 cd/m(2)), contrast
ratio (675:1, 428:1, 449:1), just-noticeable difference index (635, 622, 609),
non-uniformity (20, 5.92, and 8.5 %), veiling glare (GR = 2465.6, 720.4, 1249.8),
and color uniformity (Deltau'v' = +0.003, +0.002, +0.002). All monitors
demonstrated low noise levels. The conspicuity index (chi) of the lesions was
slightly higher in the EIZO RX850 display. All medical displays fulfilled AAPM
performance criteria, and performance characteristics of EIZO RX850 are equal to
or better than those of the Barco MDCG 5121 and EIZO GS510 displays.
PMID- 26438425
TI - Phenomenologically distinct psychotomimetic effects of ketamine are associated
with cerebral blood flow changes in functionally relevant cerebral foci: a
continuous arterial spin labelling study.
AB - RATIONALE: The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine provides
a pragmatic approach to address the link between glutamate-mediated changes in
brain function and psychosis-like experiences. Most studies using PET or BOLD
fMRI have assessed these symptoms broadly, which may limit inference about
specific mechanisms. OBJECTIVES: The objective of this study is to identify the
cerebral blood flow (CBF) correlates of ketamine-induced psychopathology,
focusing on individual psychotomimetic symptom dimensions, which may have
separable neurobiological substrates. METHODS: We measured validated
psychotomimetic symptom factors following intravenous ketamine administration in
23 healthy male volunteers (10 given a lower dose and 13 a higher dose) and
correlated ketamine-induced changes in symptoms with regional changes in CBF,
measured non-invasively using arterial spin labelling (ASL). RESULTS: The main
effect of ketamine paralleled previous studies, with increases in CBF in anterior
and subgenual cingulate cortex and decreases in superior and medial temporal
cortex. Subjective effects were greater in the high-dose group. For this group,
ketamine-induced anhedonia inversely related to orbitofrontal cortex CBF changes
and cognitive disorganisation was positively correlated with CBF changes in
posterior thalamus and the left inferior and middle temporal gyrus. Perceptual
distortion was correlated with different regional CBF changes in the low- and
high-dose groups. CONCLUSIONS: Here, we provide evidence for the sensitivity of
ASL to the effects of ketamine and the strength of subjective experience,
suggesting plausible neural mechanisms for ketamine-induced anhedonia and
cognitive disorganisation.
PMID- 26438426
TI - Rapid and high-efficiency generation of mature functional hepatocyte-like cells
from adipose-derived stem cells by a three-step protocol.
AB - The generation of functional hepatocytes is a major challenge for regenerative
medicine and drug discovery. Here we show a method that facilitates generation of
induced functional hepatocytes (iHeps) from adipose-derived stem cells (ADSCs)
within 9 days. iHeps express hepatocytic gene programs and display functions
characteristic of mature hepatocytes, including cytochrome P450 enzyme activity.
Upon transplantation into mice with carbon tetrachloride (CCl4)-induced acute
fulminant liver failure, iHeps restore the liver function and prolong survival.
The work could contribute to the development of alternative strategies to obtain
nonhepatic cell-derived mature hepatocytes with potential for biomedical and
pharmaceutical applications.
PMID- 26438427
TI - A computer simulation model of Wolbachia invasion for disease vector population
modification.
AB - BACKGROUND: Wolbachia invasion has been proved to be a promising alternative for
controlling vector-borne diseases, particularly Dengue fever. Creating computer
models that can provide insight into how vector population modification can be
achieved under different conditions would be most valuable for assessing the
efficacy of control strategies for this disease. METHODS: In this paper, we
present a computer model that simulates the behavior of native mosquito
populations after the introduction of mosquitoes infected with the Wolbachia
bacteria. We studied how different factors such as fecundity, fitness cost of
infection, migration rates, number of populations, population size, and number of
introduced infected mosquitoes affect the spread of the Wolbachia bacteria among
native mosquito populations. RESULTS: Two main scenarios of the island model are
presented in this paper, with infected mosquitoes introduced into the largest
source population and peripheral populations. Overall, the results are promising;
Wolbachia infection spreads among native populations and the computer model is
capable of reproducing the results obtained by mathematical models and field
experiments. CONCLUSIONS: Computer models can be very useful for gaining insight
into how Wolbachia invasion works and are a promising alternative for
complementing experimental and mathematical approaches for vector-borne disease
control.
PMID- 26438428
TI - Identifying binary protein-protein interactions from affinity purification mass
spectrometry data.
AB - BACKGROUND: The identification of protein-protein interactions contributes
greatly to the understanding of functional organization within cells. With the
development of affinity purification-mass spectrometry (AP-MS) techniques,
several computational scoring methods have been proposed to detect protein
interactions from AP-MS data. However, most of the current methods focus on the
detection of co-complex interactions and do not discriminate between direct
physical interactions and indirect interactions. Consequently, less is known
about the precise physical wiring diagram within cells. RESULTS: In this paper,
we develop a Binary Interaction Network Model (BINM) to computationally identify
direct physical interactions from co-complex interactions which can be inferred
from purification data using previous scoring methods. This model provides a
mathematical framework for capturing topological relationships between direct
physical interactions and observed co-complex interactions. It reassigns a
confidence score to each observed interaction to indicate its propensity to be a
direct physical interaction. Then observed interactions with high confidence
scores are predicted as direct physical interactions. We run our model on two
yeast co-complex interaction networks which are constructed by two different
scoring methods on a same combined AP-MS data. The direct physical interactions
identified by various methods are comprehensively benchmarked against different
reference sets that provide both direct and indirect evidence for physical
contacts. Experiment results show that our model has a competitive performance
over the state-of-the-art methods. CONCLUSIONS: According to the results obtained
in this study, BINM is a powerful scoring method that can solely use network
topology to predict direct physical interactions from AP-MS data. This study
provides us an alternative approach to explore the information inherent in AP-MS
data. The software can be downloaded from https://github.com/Zhangxf-ccnu/BINM.
PMID- 26438429
TI - Are brief interventions to increase physical activity cost-effective? A
systematic review.
AB - OBJECTIVE: To determine whether brief interventions promoting physical activity
are cost-effective in primary care or community settings. DESIGN: Systematic
review of economic evaluations. METHODS AND DATA SOURCES: We searched MEDLINE,
EMBASE, PsycINFO, CINAHL, EconLit, SPORTDiscus, PEDro, the Cochrane library,
National Health Service Economic Evaluation Database and the Cost-Effectiveness
Analysis Registry up to 20 August 2014. Web of Knowledge was used for cross
reference search. We included studies investigating the cost-effectiveness of
brief interventions, as defined by National Institute for Health and Care
Excellence, promoting physical activity in primary care or the community.
Methodological quality was assessed using Drummond's checklist for economic
evaluations. Data were extracted from individual studies fulfilling selection
criteria using a standardised pro forma. Comparisons of cost-effectiveness and
cost-utility ratios were made between studies. RESULTS: Of 1840 identified
publications, 13 studies fulfilled the inclusion criteria describing 14 brief
interventions. Studies varied widely in the methods used, such as the perspective
of economic analysis, intervention effects and outcome measures. The incremental
cost of moving an inactive person to an active state, estimated for eight
studies, ranged from L96 to L986. The cost-utility was estimated in nine studies
compared with usual care and varied from L57 to L14 002 per quality-adjusted life
year; dominant to L6500 per disability-adjusted life year; and L15 873 per life
years gained. CONCLUSIONS: Brief interventions promoting physical activity in
primary care and the community are likely to be inexpensive compared with usual
care. Given the commonly accepted thresholds, they appear to be cost-effective on
the whole, although there is notable variation between studies.
PMID- 26438430
TI - Increased ethanol production by deletion of HAP4 in recombinant xylose
assimilating Saccharomyces cerevisiae.
AB - The Saccharomyces cerevisiae HAP4 gene encodes a transcription activator that
plays a key role in controlling the expression of genes involved in mitochondrial
respiration and reductive pathways. This work examines the effect of knockout of
the HAP4 gene on aerobic ethanol production in a xylose-utilizing S. cerevisiae
strain. A hap4-deleted recombinant yeast strain (B42-DHAP4) showed increased
maximum concentration, production rate, and yield of ethanol compared with the
reference strain MA-B42, irrespective of cultivation medium (glucose, xylose, or
glucose/xylose mixtures). Notably, B42-DHAP4 was capable of producing ethanol
from xylose as the sole carbon source under aerobic conditions, whereas no
ethanol was produced by MA-B42. Moreover, the rate of ethanol production and
ethanol yield (0.44 g/g) from the detoxified hydrolysate of wood chips was
markedly improved in B42-DHAP4 compared to MA-B42. Thus, the results of this
study support the view that deleting HAP4 in xylose-utilizing S. cerevisiae
strains represents a useful strategy in ethanol production processes.
PMID- 26438431
TI - Natural products as probes in pharmaceutical research.
AB - From the start of the pharmaceutical research natural products played a key role
in drug discovery and development. Over time many discoveries of fundamental new
biology were triggered by the unique biological activity of natural products.
Unprecedented chemical structures, novel chemotypes, often pave the way to
investigate new biology and to explore new pathways and targets. This review
summarizes the recent results in the area with a focus on research done in the
laboratories of Novartis Institutes for BioMedical Research. We aim to put the
technological advances in target identification techniques in the context to the
current revival of phenotypic screening and the increasingly complex biological
questions related to drug discovery.
PMID- 26438433
TI - [Erratum to: Abstract-Band DOG 2015].
PMID- 26438432
TI - Rapid assay of stem cell functionality and potency using electric cell-substrate
impedance sensing.
AB - Regenerative medicine studies using autologous bone marrow mononuclear cells (BM
MNCs) have shown improved clinical outcomes that correlate to in vitro BM-MNC
invasive capacity. The current Boyden-chamber assay for testing invasive capacity
is labor-intensive, provides only a single time point, and takes 36 hours to
collect data and results, which is not practical from a clinical cell delivery
perspective. To develop a rapid, sensitive and reproducible invasion assay, we
employed Electric Cell-substrate Impedance Sensing (ECIS) technology. Chemokine
directed BM-MNC cell invasion across a Matrigel-coated Transwell filter was
measurable within minutes using the ECIS system we developed. This ECIS-Transwell
chamber system provides a rapid and sensitive test of stem and progenitor cell
invasive capacity for evaluation of stem cell functionality to provide timely
clinical data for selection of patients likely to realize clinical benefit in
regenerative medicine treatments. This device could also supply robust
unambiguous, reproducible and cost effective data as a potency assay for cell
product release and regulatory strategies.
PMID- 26438434
TI - [Evaluation of the German version of the caregiver reaction assessment
questionnaire for informal caregivers of patients with neovascular age-related
macular degeneration].
AB - BACKGROUND: Informal caregivers of patients with loss of vision often have to
give physical and emotional support because of the high level of dependence
induced. Although it is known that these informal caregivers suffer a higher risk
of being affected by burn-out syndrome or depression, the various dimensions of
burden, especially of informal caregivers of patients with neovascular age
related macular degeneration (nv-AMD) have not yet been investigated. OBJECTIVE:
The objective of this study was the evaluation of the German version of the
caregiver reaction assessment (CRA) questionnaire in a collective of informal
caregivers of patients with nv-AMD. In this context the positive and negative
influences on the informal caregivers were assessed. MATERIAL AND METHODS:
Between January 2013 and July 2014 a total of 150 informal caregivers of patients
with nv-AMD filled out the CRA independently using a questionnaire survey which
had been translated into German. Based on this collective, the psychometric
characteristics of the translated questionnaire were evaluated. RESULTS: The
informal caregivers of the current collective reported a lower burden in the five
subgroups disrupted schedule, lack of family support, self-esteem, health
problems and financial problems, compared to the previous CRA studies with
caregivers of patients with other diseases. The informal caregivers saw the
greatest burden as the disruption of their schedule. Through a principal
component analysis the five subgroups could be identified as five factors. It was
shown that 19 out of the 24 items could be assigned to the same factors as in the
original English version. The internal consistency of the five subgroups was
acceptable except for the subscale on self-esteem. CONCLUSION: In this study the
CRA has been confirmed as a suitable instrument to assess both positive and
negative reactions of informal caregivers related to caregiving of patients with
nv-AMD. The results provide support for a five subscale structure of the CRA in
the original English version but five items of the questionnaire could be
assigned to another subscale.
PMID- 26438436
TI - Cost Analysis of Intraoperative Subareolar Frozen Section During Nipple-Sparing
Mastectomy.
AB - BACKGROUND: Permanent paraffin subareolar biopsy during nipple-sparing mastectomy
(NSM) tests for occult cancer at the nipple-areolar complex. Intraoperative
subareolar frozen section can provide earlier detection intraoperatively. Cost
analysis for intraoperative subareolar frozen section has never been performed.
METHODS: NSM cases from 2006-2013 were reviewed. Patient records including
financial charges were analyzed. RESULTS: Of 480 subareolar biopsies for NSM from
2006-2013, 21 were abnormal (4.4 %). A total of 307 of the subareolar biopsies
included intraoperative frozen section. Of the 307, 12 (3.9 %) were abnormal with
7 of 12 detected on intraoperative frozen section. The median baseline charge for
an intraoperative subareolar frozen section was $309 for an estimated total cost
of $94,863 in 307 breasts. The median baseline charge for interval operative
resection of a nipple-areolar complex following an abnormal subareolar pathology
result was $11,021. Intraoperative subareolar biopsy avoided an estimated six
return trips to the operating room for savings of $66,126. At our institution,
routine use of intraoperative frozen section resulted in an additional $28,737 in
healthcare charges or $95 per breast. CONCLUSIONS: We present the first cost
analysis to evaluate intraoperative subareolar frozen section in NSM. This
practice obviated an estimated six return trips to the operating room. With our
institutional frequency of abnormal subareolar pathology, intraoperative frozen
sections resulted in a marginal increased charge per mastectomy.
PMID- 26438437
TI - Single-Port Extra- and Transperitoneal Approach for Paraaortic Lymphadenectomy in
Gynecologic Cancers: A Propensity-Adjusted Analysis.
AB - BACKGROUND: Endoscopic paraaortic lymphadenectomy (PALN), an important step in
the management of gynecologic cancers, is associated with low morbidity. However,
some concerns exist about the completeness of PALN according to the route
(transperitoneal vs. single-port extraperitoneal). METHODS: This study
retrospectively reviewed the records of patients who had undergone an endoscopic
PALN for a gynecologic cancer from May 2010 to August 2014 at the authors'
center. The findings showed that 44 patients had a single-port extraperitoneal
PALN and 56 had a transperitoneal PALN. The factors independently related to
technical performances were tested with a multivariate model adjusted for a
propensity score. RESULTS: A median of 16 lymph nodes were removed by the
transperitoneal route and 12 by the extraperitoneal route (p = 0.04). No
difference in the number of lymph nodes removed was observed after adjustment for
the propensity score of patients who underwent the extraperitoneal approach (p =
0.9). The transperitoneal route was associated with more lymphocysts (20 vs. 2%
for the extraperitoneal approach) (p = 0.008). The success rate for the
extraperitoneal PALN was 91% (n = 40), with the three remaining patients
requiring conversion to the transperitoneal route due to a peritoneal breach.
CONCLUSION: This propensity-score-adjusted study supports the conclusion that the
efficacy of the single-port extraperitoneal route is similar to that of the
transperitoneal route for PALN.
PMID- 26438438
TI - The Added Value of SPECT/CT in Sentinel Lymph Nodes Mapping for Endometrial
Carcinoma.
AB - OBJECTIVES: This study was designed to evaluate the detection rate (DR) and
sensitivity of sentinel lymph node (SLN) mapping in patients with endometrial
cancer using TC99m colloid and blue dye and to evaluate the contribution of
preoperative planar lymphoscintigraphy (PLSG) and SPECT/CT. METHODS: A
retrospective analysis of patients who underwent SLN mapping as part of their
primary surgery for endometrial cancer. Patients underwent preoperative PLSG and
later with additional SPECT/CT. Intraoperative detection was performed using
TC99m colloid and blue dye by cervical injections. SLNs were sent separately for
pathologic evaluation with ultrastaging. RESULTS: Fifty-three patients were
included in this study. Successful preoperative mapping was achieved in 31 of 37
patients (84 %) who underwent SPECT/CT compared with only 30 of 45 patients (67
%) who underwent PLSG. SPECT/CT localizations of SLNs were anatomically accurate
in 91 % of cases. Intraoperative DR of at least one SLN was 77 %, whilst the
bilateral DR was 49 %. DR was significantly better using combined blue dye and
TC99m colloid injections compared with blue dye alone: 81 versus 57 % for
unilateral and 54 versus 28 % for bilateral mapping (P = 0.01, 0.009,
respectively). Six cases of nodal metastasis were diagnosed: four by positive
SLNs, and two cases were diagnosed using side-specific full dissection according
to the SLN algorithm when SLN detection failed. There were no cases of false
negative results. CONCLUSIONS: SLN detection using cervical injections of TC99m
colloid and blue dye is feasible and sensitive for patients with endometrial
cancer. SPECT/CT aids to accurate locating of the SLN.
PMID- 26438435
TI - Genome-wide association study dissects genetic architecture underlying
longitudinal egg weights in chickens.
AB - BACKGROUND: As a major economic trait in chickens, egg weight (EW) receives
widespread interests in breeding, production and consumption. However, limited
information is available for underlying genetic architecture of longitudinal
trend in EW. Herein, we measured EWs at nine time points from onset of laying to
60 week of age, and conducted comprehensive genome-wide association studies
(GWAS) in 1,534 F2 hens derived from reciprocal crosses between White Leghorn and
Dongxiang chickens. RESULTS: Egg weights at all ages except the first egg weight
(FEW) exhibited high SNP-based heritability estimates (0.47~0.60). Strong pair
wise genetic correlations (0.77~1.00) were found among all EWs. Nine separate
univariate genome-wide screens suggested 73 signals showing significant
associations with longitudinal EWs. After multivariate and conditional analyses,
four variants on three chromosomes remained independent contributions. The minor
alleles at two loci exerted consistent and positive substitution effects on EWs,
and other two were negative. The four loci together accounted for 3.84 % of the
phenotypic variance for FEW and 7.29~11.06 % for EWs from 32 to 60 week of age.
We obtained five candidate genes, of which NCAPG harbors a non-synonymous SNP
(rs14491030) causing a valine-to-alanine amino-acid substitution. Genome
partitioning analysis indicated a strong linear correlation between the variance
explained by each chromosome and its length, which provided evidence that EW
follows a highly polygenic nature of inheritance. CONCLUSIONS: Identification of
significant genetic causes that together implicate EWs at different ages will
greatly advance our understanding of the genetic basis behind longitudinal EWs,
and would be helpful to illuminate the future breeding direction on how to select
desired egg size.
PMID- 26438439
TI - Updated Evidence of Acellular Dermal Matrix Use for Implant-Based Breast
Reconstruction: A Meta-analysis.
AB - BACKGROUND: Although the use of acellular dermal matrix (ADM) has increased
exponentially, debates regarding its safety are still ongoing. There have been
several meta-analyses; however, potential learning curve effects of using ADM
might affect their outcomes. The present meta-analysis reappraised the potential
benefits and risks of ADM on the outcome of implant-based breast reconstruction
using recent publications. METHODS: Electronic databases were searched to
identify relevant studies comparing the outcome of ADM use with traditional
submuscular technique, which were published from 2011 to 2014. The relative risks
of postoperative complications and mean difference of expander dynamics between
the two groups were computed. RESULTS: A total of 23 studies representing 6199
cases were analyzed. There was one randomized controlled study and three
prospective cohort studies. The use of ADM significantly elevated the risks of
infection, seroma, and mastectomy flap necrosis, but did not affect the risks of
implant loss, unplanned reoperation, and total complications. The risks of
capsular contracture and implant malposition were significantly reduced by the
application of ADM. The ADM allows for significantly greater intraoperative
expansion and reduced frequency of injection to complete expansion. CONCLUSIONS:
According to this meta-analysis, the increasing risks for serious complication
and overall morbidity related to ADM use might not be remarkable, while its
benefits for preventing late complications and improving expander dynamics might
be appreciable. Although future well-controlled studies would be required, the
implant-based breast reconstruction using ADM may be reliable and advantageous.
PMID- 26438440
TI - OSNA-Assisted Molecular Staging in Colorectal Cancer: A Prospective Multicenter
Trial in Japan.
AB - BACKGROUND: We previously reported that the one-step nucleic acid amplification
(OSNA) assay provided a judgment performance for colorectal cancer equivalent to
a 2-mm-interval histopathological examination of lymph nodes (concordance 97.1 %,
n = 385 lymph nodes). In this prospective multicenter study, we uncovered an OSNA
assisted pathology to detect lymph node metastasis. METHODS: A total of 204 (50
stage I, 74 stage II, and 80 stage III) colorectal cancer patients. All 4324
lymph nodes were examined by the standard histology (one-slice H&E staining) and
1925 lymph nodes (44.5 %) of them were also subject to the OSNA analysis.
RESULTS: The concordance rate between 1 slice hematoxylin/eosin and OSNA assay
was 95.7 % (1,842/1925 lymph nodes). The sensitivity and specificity of the OSNA
assay were 86.2 % (125/145) and 96.5 % (1717/1780), respectively. Among 124 node
negative patients (pN0), the respective upstaging rates of pStages I, IIA, IIB,
and IIC were 2.0 % (1/50), 17.7 % (11/62), 12.5 % (1/8), and 25 % (1/4). OSNA
positive patients had deeper invasion to the colonic wall and severe lymphatic
invasion (P = 0.048 and P = 0.004, respectively). The sum of the quantitative
results of OSNA and total tumor load increased as the number of metastasized
lymph nodes increased: 1550 copies/MUL in pN0, 24,050 copies/MUL in pN1, and
90,600 copies/MUL in pN2. CONCLUSIONS: The present study on colorectal cancer
provided fundamental data regarding OSNA-assisted pathology of lymph node
metastasis in Japan.
PMID- 26438441
TI - Complications and Postoperative Mortality Rate After Surgery for Pathological
Femur Fracture Related to Bone Metastasis: Analysis of a Nationwide Database.
AB - BACKGROUND: Currently, there are few reports regarding predictors of
postoperative complications and short-term mortality after surgery for
pathological femur fracture related to bone metastasis. METHODS: Using data from
the Japanese Diagnosis Procedure Combination Database from 2007 to 2012, we
retrospectively identified 1497 patients who underwent internal fixation (n =
1073) or proximal femur resection and endoprosthetic reconstruction of the
proximal femur (n = 424) for pathological femur fracture related to bone
metastasis. Multivariable logistic regression analysis was performed to examine
the relationship of various factors with postoperative complications and 30-day
mortality. RESULTS: The overall 30-day mortality after surgery was 2.6%, and the
proportion of postoperative complications was 12.1%. Multivariable logistic
regression analysis showed that postoperative complications overall were
significantly associated with older age [odds ratio (OR), 2.15; 95% confidence
interval (CI) 1.23-3.74 for age >=80 vs. <=59 years]; lung carcinoma (OR 2.05;
95% CI 1.47-2.86); esophageal carcinoma (OR 4.41; 95% CI 1.57-12.43); higher
Charlson Comorbidity Index (OR 1.50; 95% CI 1.03-2.18 for >=9 vs. 8); and blood
transfusion (OR 1.57; 95% CI 1.14-2.15). Thirty-day mortality also was
significantly higher in patients with rapid-growth tumors, visceral metastasis,
internal fixation, and no postoperative chemotherapy in the univariate analysis.
CONCLUSIONS: Older age, type of primary tumor, higher Charlson Comorbidity Index,
and blood transfusion were associated with higher morbidity. These findings can
provide important information to assess perioperative risk in patients with
pathological femur fracture related to bone metastasis.
PMID- 26438442
TI - Enhanced Neurobehavioral Outcomes of Action Observation Prosthesis Training.
AB - Background Previous studies have demonstrated improved neurobehavioral outcomes
when prosthesis users learn task-specific behaviors by imitating movements of
prosthesis users (matched limb) compared with intact limbs (mismatched limb).
Objective This study is the first to use a unique combination of
neurophysiological and task performance methods to investigate prosthetic device
training strategies from a cognitive motor control perspective. Intact
nonamputated prosthesis users (NAPUs) donned specially adapted prosthetic devices
to simulate the wrist and forearm movement that persons with transradial limb
loss experience. The hypothesis is that NAPUs trained with matched limb imitation
would show greater engagement of parietofrontal regions and reduced movement
variability compared with their counterparts trained with a mismatched limb.
Methods Training elapsed over 3 days comprised alternating periods of video
demonstration observation followed by action imitation. At the beginning and end
of the training protocol, participants performed a cued movement paradigm while
electroencephalography and electrogoniometry data were collected to track changes
in cortical activity and movement variability, respectively. Results Matched limb
participants showed greater engagement of motor-related areas while mismatched
limb participants showed greater engagement of the parietooccipital system.
Matched limb participants also showed lower movement variability. Conclusions
These results indicate that the type of limb imitated influences neural and
behavioral strategies for novel prosthetic device usage. This finding is
important, as customary prosthetic rehabilitation with intact therapists involves
mismatched limb imitation that may exacerbate challenges in adapting to new motor
patterns demanded by prosthesis use.
PMID- 26438443
TI - Innate Lymphoid Cells in Cancer.
AB - The world of lymphocytes has recently expanded. A group of cells, innate lymphoid
cells (ILC), has been defined. It includes lymphoid cells that have been known
for decades, such as natural killer (NK) cells and lymphoid tissue-inducer (LTi)
cells. NK cells recognize a vast array of tumor cells, which they help to
eliminate through cytotoxicity and the production of cytokines, such as IFNgamma.
Advances in our understanding of NK-cell biology have led to a growing interest
in the clinical manipulation of these cells in cancer. The other ILCs are found
mostly in the mucosae and mucosal-associated lymphoid tissues, where they rapidly
initiate immune responses to pathogens without the need for specific
sensitization. Here, we outline the basic features of ILCs and review the role of
ILCs other than NK cells in cancer. Much of the role of these ILCs in cancer
remains unknown, but several findings should lead to further efforts to dissect
the contribution of different ILC subsets to the promotion, maintenance, or
elimination of tumors at various anatomic sites. This will require the
development of standardized reagents and protocols for monitoring the presence
and function of ILCs in human blood and tissue samples.
PMID- 26438444
TI - T-cell-based Immunotherapy: Adoptive Cell Transfer and Checkpoint Inhibition.
AB - Tumor immunotherapy has had demonstrable efficacy in patients with cancer. The
most promising results have been with T-cell-based therapies. These include
adoptive cell transfer of tumor-infiltrating lymphocytes, genetically engineered
T cells, and immune checkpoint inhibitor antibodies. In this review, we describe
the different T-cell-based strategies currently in clinical trials and put their
applications, present and future, into perspective.
PMID- 26438445
TI - Theoretical and experimental studies on three new coordination complexes of
Co(II), Ni(II), and Cu(II) with 2,4-dichloro-6-{(E)-[(5-chloro-2
sulfanylphenyl)imino]methyl}phenol Schiff base ligand.
AB - Three mononuclear coordination complexes of Co(II), Ni(II), and Cu(II) have been
synthesized from 2,4-dichloro-6-{(E)-[(5-chloro-2
sulfanylphenyl)imino]methyl}phenol ligand (H 2 L) obtained by simple condensation
reaction of 3,5-dichloro-2-hydroxybenzaldehyde and 2-amino-4-chlorobenzenethiol
and characterized by elemental analysis, spectral (FT-IR, electronic, and (1)H
NMR), molar conductance, thermal, SEM, PXRD, and fluorescence studies. The PXRD
analysis and SEM-EDX micrographs show the crystalline nature of complexes. The
domain size and the lattice strain of synthesized compounds have been determined
according to Williamson-Hall plot. TG of the synthesized complexes illustrates
the general decomposition pattern of the complexes. The ligand exhibits an
interesting fluorescence property which is suppressed after complex formation.
The Co(II) complex adopted a distorted octahedral configuration while Ni(II) and
Cu(II) complexes showed square planar geometry around metal center. The geometry
optimization, HOMO-LUMO, molecular electrostatic potential map (MEP), and spin
density of synthesized compounds have been performed by density functional theory
(DFT) method using B3LYP/6-31G and B3LYP/LANL2DZ as basis set. Graphical abstract
Three new coordination complexes of Co(II), Ni(II) and Cu(II) with 2,4-dichloro-6
{(E)-[(5-chloro-2 sulfanylphenyl)imino]methyl}phenol Schiff base ligand.
PMID- 26438446
TI - The CO oxidation mechanism on small Pd clusters. A theoretical study.
AB - CO is a pollutant that is removed by oxidation using Pd, Pt or Rh as catalysts in
the exhaust pipes of vehicles. Here, a quantum chemistry study on the CO + O2
reaction catalyzed by small Pdn clusters (n <= 5) using the PBE/TZ2P/ZORA method
is performed. The limiting step in this reaction at low temperature and coverage
is the O2 dissociation. Pdn clusters catalyze the O=O bond breaking, reducing the
energy barrier from 119 kcal mol(-1) without catalyst to ~35 kcal mol(-1). The
charge transfer from Pd to the O2,ad antibonding orbital weakens, and finally
breaks the O?O bond. The CO oxidation takes place by the Eley-Rideal (ER)
mechanism or the Langmuir-Hinshelwood (LH) mechanism. The ER mechanism presents
an energy barrier of 4.10-7.05 kcal mol(-1) and the formed CO2 is released after
the reaction. The LH mechanism also shows barrier energies to produce CO2 (7-15
kcal mol(-1)) but it remains adsorbed on Pd clusters. An additional energy (7-25
kcal mol(-1)) is necessary to desorb CO2 and release the metal site. The triplet
multiplicity is the ground states of studied Pdn clusters, with the following
order of stability: triplet > singlet > quintet state. Graphical Abstract CO
oxidation mechanism on small Pd clusters.
PMID- 26438447
TI - Patchy Invasion of Stage-Structured Alien Species with Short-Distance and Long
Distance Dispersal.
AB - Understanding of spatiotemporal patterns arising in invasive species spread is
necessary for successful management and control of harmful species, and
mathematical modeling is widely recognized as a powerful research tool to achieve
this goal. The conventional view of the typical invasion pattern as a continuous
population traveling front has been recently challenged by both empirical and
theoretical results revealing more complicated, alternative scenarios. In
particular, the so-called patchy invasion has been a focus of considerable
interest; however, its theoretical study was restricted to the case where the
invasive species spreads by predominantly short-distance dispersal. Meanwhile,
there is considerable evidence that the long-distance dispersal is not an exotic
phenomenon but a strategy that is used by many species. In this paper, we
consider how the patchy invasion can be modified by the effect of the long
distance dispersal and the effect of the fat tails of the dispersal kernels.
PMID- 26438448
TI - Non-invasive Characterization of Immune Responses to Biomedical Implants.
AB - Biomedical implants play an important role in today's clinical practice.
Unfortunately, biomedical implant-mediated host responses may lead to implant
failure. Thus, all implants are tested for tissue compatibility prior to clinical
trials. For that, after implantation in animals for different periods of time,
the implants and surrounding tissues are isolated for histological analyses.
Unfortunately, histological evaluation methods are labor intensive, time
consuming, expensive and do not produce quantitative outcomes. With the advent of
in vivo imaging technology, many imaging methods have been developed for
evaluating biomedical implant-associated immune responses. In this review, we
summarize the recent progress in the use of in vivo real-time imaging techniques
for assessing acute phase foreign body reactions, including fibrin deposition,
inflammatory cell recruitment and responses surrounding biomaterial implants.
These new technologies may serve as powerful tools to characterize tissue
compatibility of medical implants.
PMID- 26438449
TI - Shrinking the Supply Chain for Implantable Coronary Stent Devices.
AB - Stenting treatments for the management of disease in the heart, arterial and
venous systems, biliary ducts, urethras, ureters, oesophageal tract and prostate
have made enormous technical advances since their introduction into clinical use.
The progression from metallic to polymer based bio-absorbable stents, coupled
with the advances in additive manufacturing techniques, present a unique
opportunity to completely re-envision the design, manufacture, and supply chain
of stents. This paper looks at current stenting trends and proposes a future
where the stent supply chain is condensed from ~150 days to ~20 min. The
Cardiologist therefore has the opportunity to become a designer, manufacturer and
user with patients receiving custom stents specific to their unique pathology
that will be generated, delivered and deployed in the Cath-lab. The paper will
outline this potentially revolutionary development and consider the technical
challenges that will need to be overcome in order to achieve these ambitious
goals. A high level overview of the generating eluting stents in situ program
GENESIS-is outlined including some early experimental work.
PMID- 26438450
TI - Fatigue of Metallic Stents: From Clinical Evidence to Computational Analysis.
AB - The great success of stents in treating cardiovascular disease is actually
undermined by their long-term fatigue failure. The high variability of stent
failure incidence suggests that it is due to several correlated aspects, such as
loading conditions, material properties, component design, surgical procedure,
and patient functional anatomy. Numerical and experimental non-clinical
assessments are included in the recommendations and requirements of several
regulatory bodies and they are thus exploited in the analysis of stent fatigue
performance. Optimization-based simulation methodologies have been developed as
well, to improve the fatigue endurance of novel designs. This paper presents a
review on the fatigue issue in metallic stents, starting from a description of
clinical evidence about stent fracture up to the analysis of computational
approaches available from the literature. The reported discussion on both the
experimental and numerical framework aims at providing a general insight into
stent lifetime prediction as well as at understanding the factors which affect
stent fatigue performance for the design of novel components.
PMID- 26438451
TI - Evaluation of the Early In Vivo Response of a Functionally Graded Macroporous
Scaffold in an Osteochondral Defect in a Rabbit Model.
AB - Cartilage tissue engineering is a multifactorial problem requiring a wide range
of material property requirements from provision of biological cues to
facilitation of mechanical support in load-bearing diarthrodial joints. The study
aim was to design, fabricate and characterize a template to promote endogenous
cell recruitment for enhanced cartilage repair. A polylactic acid poly-epsilon
caprolactone (PLCL) support structure was fabricated using laser micromachining
technology and thermal crimping to create a functionally-graded open pore network
scaffold with a compressive modulus of 9.98 +/- 1.41 MPa and a compressive stress
at 50% strain of 8.59 +/- 1.35 MPa. In parallel, rabbit mesenchymal stem cells
were isolated and their growth characteristics, morphology and multipotency
confirmed. Sterilization had no effect on construct chemical structure and
cellular compatibility was confirmed. After four weeks implantation in an
osteochondral defect in a rabbit model to assess biocompatibility, there was no
evidence of inflammation or giant cells. Moreover, acellular constructs performed
better than cell-seeded constructs with endogenous progenitor cells homing
through microtunnels, differentiating to form neo-cartilage and strengthening
integration with native tissue. These results suggest, albeit at an early stage
of repair, that by modulating the architecture of a macroporous scaffold, pre
seeding with MSCs is not necessary for hyaline cartilage repair.
PMID- 26438452
TI - Emergency Neurologic Life Support (ENLS): Evolution of Management in the First
Hour of a Neurological Emergency.
AB - Emergency neurological life support (ENLS) is an educational program designed to
provide users advisory instruction regarding management for the first few hours
of a neurological emergency. The content of the course is divided into 14
modules, each addressing a distinct category of neurological injury. The course
is appropriate for practitioners and providers from various backgrounds who work
in environments of variable medical complexity. The focus of ENLS is centered on
a standardized treatment algorithm, checklists to guide early patient care, and a
structured format for communication of findings and concerns to other healthcare
professionals. Certification and training in ENLS is hosted by the Neurocritical
Care Society. This document introduces the concept of ENLS and describes the
revisions that constitute this second version.
PMID- 26438453
TI - Emergency Neurological Life Support: Acute Ischemic Stroke.
AB - Acute ischemic stroke is a neurological emergency that can be treated with time
sensitive interventions, including intravenous thrombolysis and endovascular
approaches. Extensive study has demonstrated that rapid assessment and treatment
are essential for improving neurological outcome. For this reason, acute ischemic
stroke was chosen as an Emergency Neurological Life Support protocol. The
protocol focuses on the first hour following the onset of neurological deficit.
PMID- 26438454
TI - Emergency Neurological Life Support: Pharmacotherapy.
AB - The appropriate use of medications during Emergency Neurological Life Support
(ENLS) is essential to optimize patient care. Important considerations when
choosing the appropriate agent include the patient's organ function and
medication allergies, potential adverse drug effects, drug interactions, and
critical illness and aging pathophysiologic changes. Critical medications used
during ENLS include hyperosmolar therapy, anticonvulsants, antithrombotics,
anticoagulant reversal and hemostatic agents, anti-shivering agents,
neuromuscular blockers, antihypertensive agents, sedatives, vasopressors and
inotropes, and antimicrobials. This article focuses on the important
pharmacokinetic and pharmacodynamics characteristics, advantages and
disadvantages, and clinical pearls of these therapies, providing practitioners
with essential drug information to optimize pharmacotherapy in acutely ill
neurocritical care patients.
PMID- 26438455
TI - Emergency Neurological Life Support: Acute Non-traumatic Weakness.
AB - Acute non-traumatic weakness may be life threatening if it involves the
respiratory muscles or is associated with autonomic dysfunction. Most patients
presenting with acute muscle weakness have a worsening neurological disorder that
requires a rapid, systematic evaluation, and detailed neurological exam to
localize the disorder. Urgent laboratory tests and neuroimaging are needed in
many patients to make the diagnosis. Because acute weakness is a common
presenting sign of neurological emergencies, it was chosen as an Emergency
Neurological Life Support protocol. Causes of acute non-traumatic weakness are
discussed by both presenting clinical signs and anatomical location. For each
diagnosis, key features of the history, examination, investigations, and
treatment are outlined in the included tables.
PMID- 26438456
TI - Emergency Neurologic Life Support: Meningitis and Encephalitis.
AB - Bacterial meningitis and viral encephalitis, particularly herpes simplex
encephalitis, are severe neurological infections that, if not treated promptly
and effectively, lead to poor neurological outcome or death. Because treatment is
more effective if given early, the topic of meningitis and encephalitis was
chosen as an Emergency Neurological Life Support protocol. This protocol provides
a practical approach to recognition and urgent treatment of bacterial meningitis
and encephalitis. Appropriate imaging, spinal fluid analysis, and early empiric
treatment is discussed. Though uncommon in its full form, the typical clinical
triad of headache, fever, and neck stiffness should alert the clinical
practitioner to the possibility of a central nervous system infection. Early
attention to the airway and maintaining normotension is crucial in treatment of
these patients, as is rapid treatment with anti-infectives and, in some cases,
corticosteroids.
PMID- 26438458
TI - Emergency Neurologic Life Support: Spinal Cord Compression.
AB - There are many causes of acute myelopathy including multiple sclerosis, systemic
disease (SD), and acute spinal cord compression (SCC). SCC should be among the
first potential causes considered given the significant permanent loss of
neurologic function commonly associated with SCC. This impairment can occur over
a short period of time, and may be avoided through rapid and acute surgical
intervention. Patients with SCC typically present with a combination of motor and
sensory dysfunction that has a distribution referable to a spinal level. Bowel
and bladder dysfunction and neck or back pain may also be part of the clinical
presentation, but are not uniformly present. Because interventions are critically
time-sensitive, the recognition and treatment of SCC was chosen as an ENLS
protocol.
PMID- 26438457
TI - Emergency Neurological Life Support: Airway, Ventilation, and Sedation.
AB - Airway management and ventilation are central to the resuscitation of the
neurologically ill. These patients often have evolving processes that threaten
the airway and adequate ventilation. Furthermore, intubation, ventilation, and
sedative choices directly affect brain perfusion. Therefore, airway, ventilation,
and sedation was chosen as an emergency neurological life support protocol.
Topics include airway management, when and how to intubate with special attention
to hemodynamics and preservation of cerebral blood flow, mechanical ventilation
settings, and the use of sedative agents based on the patient's neurological
status.
PMID- 26438459
TI - Emergency Neurological Life Support: Intracranial Hypertension and Herniation.
AB - Sustained intracranial hypertension and acute brain herniation are "brain codes,"
signifying catastrophic neurological events that require immediate recognition
and treatment to prevent irreversible injury and death. As in cardiac arrest, a
brain code mandates the organized implementation of a stepwise management
algorithm. The goal of this emergency neurological life support protocol is to
implement an evidence-based, standardized approach to the evaluation and
management of patients with intracranial hypertension and/or herniation.
PMID- 26438460
TI - Emergency Neurological Life Support: Traumatic Spine Injury.
AB - Traumatic spine injuries (TSIs) carry significantly high risks of morbidity,
mortality, and exorbitant health care costs from associated medical needs
following injury. For these reasons, TSI was chosen as an ENLS protocol. This
article offers a comprehensive review on the management of spinal column injuries
using the best available evidence. Alhough the review focuses primarily on
cervical spinal column injuries, thoracolumbar injuries are briefly discussed as
well. The initial emergency department clinical evaluation of possible spinal
fractures and cord injuries, along with the definitive early management of
confirmed injuries, is also covered.
PMID- 26438461
TI - Emergency Neurological Life Support: Intracerebral Hemorrhage.
AB - Intracerebral hemorrhage (ICH) is a subset of stroke due to bleeding within the
parenchyma of the brain. It is potentially lethal, and survival depends on
ensuring an adequate airway, reversal of coagulopathy, and proper diagnosis. ICH
was chosen as an Emergency Neurological Life Support protocol because
intervention within the first critical hour may improve outcome, and it is
critical to have site-specific protocols to drive care quickly and efficiently.
PMID- 26438462
TI - Emergency Neurological Life Support: Status Epilepticus.
AB - Patients with prolonged or rapidly recurring convulsions lasting more than 5 min
are in status epilepticus (SE) and require immediate resuscitation. Although
there are relatively few randomized clinical trials, available evidence and
experience suggest that early and aggressive treatment of SE improves patient
outcomes, for which reason this was chosen as an Emergency Neurological Life
Support protocol. The current approach to the emergency treatment of SE
emphasizes rapid initiation of adequate doses of first-line therapy, as well as
accelerated second-line anticonvulsant drugs and induced coma when these fail,
coupled with admission to a unit capable of neurological critical care and
electroencephalography monitoring. This protocol will focus on the initial
treatment of SE but also review subsequent steps in the protocol once the patient
is hospitalized.
PMID- 26438464
TI - Emergency Neurological Life Support: Approach to the Patient with Coma.
AB - Coma is an acute failure of neuronal systems governing arousal and awareness and
represents a medical emergency. When encountering a comatose patient, the
clinician must have an organized approach to detect easily remediable causes,
prevent ongoing neurologic injury, and determine a hierarchical plan for
diagnostic tests, treatments, and neuromonitoring. Coma was chosen as an
Emergency Neurological Life Support protocol because timely medical and surgical
interventions can be life-saving, and the initial work-up of such patients is
critical to establishing a correct diagnosis.
PMID- 26438463
TI - Emergency Neurological Life Support: Resuscitation Following Cardiac Arrest.
AB - Cardiac arrest is the most common cause of death in North America. Neurocritical
care interventions, including targeted temperature management (TTM), have
significantly improved neurological outcomes in patients successfully
resuscitated from cardiac arrest. Therefore, resuscitation following cardiac
arrest was chosen as an emergency neurological life support protocol. Patients
remaining comatose following resuscitation from cardiac arrest should be
considered for TTM. This protocol will review induction, maintenance, and re
warming phases of TTM, along with management of TTM side effects. Aggressive
shivering suppression is necessary with this treatment to ensure the maintenance
of a target temperature. Ancillary testing, including electrocardiography,
computed tomography and/or magnetic resonance imaging of the brain, continuous
electroencephalography monitoring, and correction of electrolyte, blood gas, and
hematocrit changes, are also necessary to optimize outcomes.
PMID- 26438465
TI - Emergency Neurological Life Support: Subarachnoid Hemorrhage.
AB - Subarachnoid hemorrhage (SAH) is a neurological emergency because it may lead to
sudden neurological decline and death and, depending on the cause, has treatment
options that can return a patient to normal. Because there are interventions that
can be life-saving in the first hour of onset, SAH was chosen as an Emergency
Neurological Life Support protocol.
PMID- 26438466
TI - Emergency Neurological Life Support: Traumatic Brain Injury.
AB - Traumatic Brain Injury (TBI) was chosen as an Emergency Neurological Life Support
topic due to its frequency, the impact of early intervention on outcomes for
patients with TBI, and the need for an organized approach to the care of such
patients within the emergency setting. This protocol was designed to enumerate
the practice steps that should be considered within the first critical hour of
neurological injury.
PMID- 26438467
TI - CSF Volumetric Analysis for Quantification of Cerebral Edema After Hemispheric
Infarction.
AB - BACKGROUND: Malignant cerebral edema (CED) complicates at least 20 % of large
hemispheric infarcts (LHI) and may result in neurological deterioration or death.
Midline shift (MLS) is a standard but crude measure of edema severity. We propose
that volumetric analysis of shifts in cerebrospinal fluid (CSF) over time
provides a reliable means of quantifying the spectrum of edema severity after
LHI. METHODS: We identified 38 patients from 2008 to 2014 with NIHSS >=8,
baseline CT <6 h after stroke onset, at least 1 follow-up (FU) CT, and no
parenchymal hematoma. The volumes of CSF (sulci, ventricles, and cisterns)
ipsilateral (IL) and contralateral (CL) to infarct on baseline and FU CTs were
quantified by manually assisted outlining with MIPAV image analysis software, as
was infarct volume and MLS on FU CTs. Percentage change in CSF volumes (?CSF)
from baseline to FU scans was correlated with MLS and compared in those with vs.
without malignant edema (defined as hemicraniectomy, osmotic therapy, or
death/neurological deterioration with MLS >=5 mm). RESULTS: 11 of 38 subjects (29
%) developed malignant edema. Neither baseline NIHSS nor CSF volume differed
between those with and without edema (median NIHSS 18 vs. 13, p = 0.12, CSF
volume 102 vs. 124 ml, p = 0.16). Inter-rater reliability for CSF measurements
was excellent (intraclass correlation coefficient 0.97). ?CSF correlated strongly
with MLS at peak edema (r = -0.75), even adjusting for infarct volume (p =
0.009). ?CSF was also greater in those with malignant edema [-55 % (IQR -49 to
62) vs. -36 % (-27 to -45), p = 0.004]. ?CSF was the greatest within IL sulci [
97 % (-86 to -99) vs. -71 % (-41 to -79), p = 0.002] but also significantly
greater within CL sulci in those with malignant edema [-50 % (-29 to -65) vs. -25
% (0 to -31), p = 0.014]. More than half this CSF volume reduction occurred by
the time of first FU CT around 24 h after stroke, while MLS rose later.
CONCLUSIONS: Volumetric CSF analysis reliably quantifies CED and distinguishes
those with malignant edema and MLS from those with a more benign course after
LHI. ?CSF may provide an earlier and more sensitive indicator of edema severity
across a broader dynamic range than MLS.
PMID- 26438468
TI - Changes in Depression Subtypes Among Men in STAR*D: A Latent Transition Analysis.
AB - The burden of depression in men is high. Current diagnostic criteria may not
fully capture men's experience with depression. Descriptions of the heterogeneity
in depression among men are lacking. The purpose of the study was to characterize
latent subtypes of major depression and changes in these subtypes among men
receiving citalopram in Level 1 of the Sequenced Treatment Alternatives to
Relieve Depression (STAR*D) trial. Latent transition analysis was applied to data
from 387 men who completed baseline and Week 12 study visits in Level 1 of
STAR*D. Items from the self-report version of the Quick Inventory of Depressive
Symptomatology were used as indicators of latent depression subtypes. Four
statuses were identified at baseline and Week 12. Baseline statuses were Mild
(10% of men), Moderate (53%), Severe with Psychomotor Slowing (20%), and Severe
with Psychomotor Agitation (17%). At Week 12, the statuses were Symptom
Resolution (41%), Mild (36%), Moderate (18%), and Severe with Psychomotor Slowing
(5%). Men in the Mild status were most likely to transition to Symptom Resolution
(probability = 69%). Men in the Severe with Agitation status were least likely to
transition to Symptom Resolution (probability = 0%). This work highlights the
need to not focus solely on summary rating scores but to also consider patterns
of symptoms when treating depression.
PMID- 26438469
TI - Falls and Depression in Men: A Population-Based Study.
AB - The link between falls and depression has been researched in the elderly;
however, little information is available on this association in younger adults,
particularly men. This study sought to investigate the link between major
depressive disorder (MDD) and falls in a population-based sample of 952 men (24
97 years). MDD was diagnosed utilizing the Structured Clinical Interview for DSM
IV-TR Research Version, Non-Patient edition, and categorized as 12
month/past/never. Body mass index and gait were measured; falls, smoking status,
psychotropic medication use, and alcohol intake were self-reported as part of the
Geelong Osteoporosis Study 5-year follow-up assessment. Thirty-four (3.6%) men
met criteria for 12-month MDD, and 110 (11.6%) for past MDD. Of the 952 men, 175
(18.4%) reported falling at least once during the past 12 months. Fallers were
older (66 [interquartile range: 48-79] vs. 59 [45-72] years, p = .001) and more
likely to have uneven gait ( n = 16, 10% vs. n = 31, 4%, p = .003) than
nonfallers. Participants with 12-month MDD had more than twice the odds of
falling (age-adjusted odds ratio: 2.22, 95% confidence interval [1.03, 4.80]).
The odds of falling were not associated with past depression ( p = .4). Further
adjustments for psychotropic drug use, gait, body mass index, smoking status,
blood pressure, and alcohol did not explain these associations. Given the 2.2
fold greater likelihood of falling associated with depression was not explained
by age or psychotropic drug use, further research is warranted.
PMID- 26438471
TI - The Effect of Testosterone Topical Solution in Hypogonadal Men With Suboptimal
Response to a Topical Testosterone Gel.
AB - This study evaluated the effect of axillary administration of a 2% testosterone
solution (Axiron(r)) in hypogonadal (HGN) men who had had a suboptimal response
to treatment with a commercially available topical testosterone gel. HGN men
averaging 57 years old, with a mean body mass index of 31.9 kg/m2 and median
baseline testosterone level (T-level) of 185.2 ng/dL, who had failed to reach
normal T-levels with a topical testosterone gel (Androgel 1.62%, Androgel,
Testim, or Fortesta) were treated with a 2% testosterone solution until T-levels
reached a normal range (from >=300 to <=1,050 ng/dL) or for up to 9 weeks.
Outcomes included the cumulative percentage of men with a serum T-level in the
normal range during treatment with Axiron and improvement in symptoms of low
energy level and low sexual drive. During the study, 95% of HGN men (72/78)
attained a T-level in the normal range. The median T-level at endpoint was 495.7
ng/dL, a threefold increase over baseline, p < .001, 70% achieving normal T
levels within the first 2 weeks of treatment. In a post hoc analysis, all
subjects with baseline body mass indexes >35 kg/m2 ( n = 19) achieved T-levels in
the normal range. Prior to treatment, over 61% of subjects (48/78) reported
impairment in either energy level or sexual drive. After treatment (or
testosterone normalization), energy level improved in 75% of subjects and sexual
drive improved in 70%. Topical 2% testosterone solution is a safe and effective
treatment for HGN men who have had a suboptimal response to previous treatment
with topical testosterone gels.
PMID- 26438470
TI - Transactional Sex With Regular and Casual Partners Among Young Men Who Have Sex
With Men in the Detroit Metro Area.
AB - Transactional sex refers to the commodification of the body in exchange for
shelter, food, and other goods and needs. Transactional sex has been associated
with negative health outcomes including HIV infection, psychological distress,
and substance use and abuse. Compared with the body of research examining
transactional sex among women, less is known about the prevalence and correlates
of transactional sex among men. Using data from a cross-sectional survey of young
men who have sex with men (ages 18-29) living in the Detroit Metro Area ( N =
357; 9% HIV infected; 49% Black, 26% White, 16% Latino, 9% Other race),
multivariate logistic regression analyses examined the association between
transactional sex with regular and casual partners and key psychosocial factors
(e.g., race/ethnicity, education, poverty, relationship status, HIV status, prior
sexually transmitted infections [STIs], mental health, substance use, and
residential instability) previously identified in the transactional sex
literature. Forty-four percent of the current sample reported engaging in
transactional sex. Transactional sex was associated with age, employment status,
relationship status, and anxiety symptoms. When stratified, transactional sex
with a regular partner was associated with age, educational attainment,
employment status, relationship status, anxiety, and alcohol use. Transactional
sex with a casual partner was associated with homelessness, race/ethnicity,
employment status, and hard drug use. The implications of these findings for
HIV/STI prevention are discussed, including the notion that efforts to address
HIV/STIs among young men who have sex with men may require interventions to
consider experiences of transactional sex and the psychosocial contexts that may
increase its likelihood.
PMID- 26438472
TI - Comparative study of 13C composition in ethanol and bulk dry wine using isotope
ratio monitoring by mass spectrometry and by nuclear magnetic resonance as an
indicator of vine water status.
AB - The potential of wine (13)C isotope composition (delta(13)C) is presented to
assess vine water status during grape ripening. Measurements of delta(13)C have
been performed on a set of 32 authentic wines and their ethanol recovered after
distillation. The data, obtained by isotope ratio monitoring by mass spectrometry
coupled to an elemental analyser (irm-EA/MS), show a high correlation between
delta(13)C of the bulk wine and its ethanol, indicating that the distillation
step is not necessary when the wine has not been submitted to any oenological
treatment. Therefore, the ethanol/wine delta(13)C correlation can be used as an
indicator of possible enrichment of the grape must or the wine with exogenous
organic compounds. Wine ethanol delta(13)C is correlated to predawn leaf water
potential (R(2) = 0.69), indicating that this parameter can be used as an
indicator of vine water status. Position-specific (13)C analysis (PSIA) of
ethanol extracted from wine, performed by isotope ratio monitoring by nuclear
magnetic resonance (irm-(13)C NMR), confirmed the non-homogenous repartition of
(13)C on ethanol skeleton. It is the delta(13)C of the methylene group of
ethanol, compared to the methyl moiety, which is the most correlated to predawn
leaf water potential, indicating that a phase of photorespiration of the vine
during water stress period is most probably occurring due to stomata closure.
However, position-specific (13)C analysis by irm-(13)C NMR does not offer a
greater precision in the assessment of vine water status compared to direct
measurement of delta(13)C on bulk wine by irm-EA/MS.
PMID- 26438473
TI - Accelerated separation of GC-amenable lipid classes in plant oils by
countercurrent chromatography in the co-current mode.
AB - Triacylglycerols represent the major part (>90%) in most plant oils and have to
be eliminated, when the minor compounds such as phytosterols or tocopherols
should be analyzed. Here, we used an all liquid-liquid chromatographic technique,
countercurrent chromatography (CCC), to fractionate the minor lipids before gas
chromatography (GC) analysis. To cover the wide range of polarity of the minor
compounds, we used the co-current mode, in which both mobile and stationary phase
are pumped through the system. This allowed to elute substances which partitioned
almost exclusively in the stationary phase within 90 min. After testing with
standard compounds, the method was applied to the separation of sesame oil and
sunflower oil samples. The abundant triacylglycerols could be effectively
separated from tocopherols, phytosterols, diacylglycerols, and free fatty acids
in the samples, and these compounds could be analyzed (after trimethylsilylation)
by GC coupled with mass spectrometry. After the enrichment caused by the CCC
fractionation, we were also able to identify the tocopherol derivative alpha
tocomonoenol, which had not been described in sunflower oil before. Also,
separation of sesame oil yielded a mixture of the polar compounds sesamin and
sesamolin without further impurities.
PMID- 26438475
TI - Introduction of regulations for arsenic in feed and food with emphasis on
inorganic arsenic, and implications for analytical chemistry.
PMID- 26438476
TI - Nanospectroscopy.
PMID- 26438477
TI - MC ICP-MS delta(34)S(VCDT) measurement of dissolved sulfate in environmental
aqueous samples after matrix separation by means of an anion exchange membrane.
AB - Analysis of (34)S/(32)S of sulfate in rainwater and soil solutions can be seen as
a powerful tool for the study of the sulfur cycle. Therefore, it is considered as
a useful means, e.g., for amelioration and calibration of ecological or
biogeochemical models. Due to several analytical limitations, mainly caused by
low sulfate concentration in rainwater, complex matrix of soil solutions, limited
sample volume, and high number of samples in ecosystem studies, a straightforward
analytical protocol is required to provide accurate S isotopic data on a large
set of diverse samples. Therefore, sulfate separation by anion exchange membrane
was combined with precise isotopic measurement by multicollector inductively
coupled plasma mass spectrometry (MC ICP-MS). The separation method proved to be
able to remove quantitatively sulfate from matrix cations (Ca, K, Na, or Li)
which is a precondition in order to avoid a matrix-induced analytical bias in the
mass spectrometer. Moreover, sulfate exchange on the resin is capable of
preconcentrating sulfate from low concentrated solutions (to factor 3 in our
protocol). No significant sulfur isotope fractionation was observed during
separation and preconcentration. MC ICP-MS operated at edge mass resolution has
enabled the direct (34)S/(32)S analysis of sulfate eluted from the membrane, with
an expanded uncertainty U (k = 2) down to 0.3 0/00 (a single measurement). The
protocol was optimized and validated using different sulfate solutions and
different matrix compositions. The optimized method was applied in a study on
solute samples retrieved in a beech (Fagus sylvatica) forest in the Vienna Woods.
Both rainwater (precipitation and tree throughfall) and soil solution delta
(34)SVCDT ranged between 4 and 6 0/00, the ratio in soil solution being slightly
lower. The lower ratio indicates that a considerable portion of the
atmospherically deposited sulfate is cycled through the organic S pool before
being released to the soil solution. Nearly the same trends and variations were
observed in soil solution and rainwater delta (34)SVCDT values showing that
sulfate adsorption/desorption are not important processes in the studied soil.
PMID- 26438478
TI - Real-time cdPCR opens a window into events occurring in the first few PCR
amplification cycles.
AB - Polymerase chain reaction (PCR) end-point limiting dilution techniques,
collectively termed "digital PCR (dPCR)", have been proposed as providing a
potentially primary method for DNA quantification. We are evaluating several
commercially available dPCR systems for use in certifying mass concentration in
human genomic DNA reference materials. To better understand observed anomalies
among results from chamber- and droplet-dPCR (cdPCR and ddPCR) systems, we have
developed a graphical tool for evaluating and documenting the performance of PCR
assays in real-time cdPCR systems: the ogive plot, the cumulative distribution of
crossing threshold values. The ogive structure appears to embed information about
early amplification events. We have successfully simulated ogives observed with
different assays and reaction conditions using a four-stage amplification model
parameterized by the probability of creating an intact 1) first generation "long"
amplicon of indeterminate length from an original DNA target, 2) second
generation defined-length amplicon from a long amplicon, and 3) defined-length
amplicon from another defined-length amplicon. We are using insights from this
model to optimize dPCR assay design and reaction conditions and to help validate
assays proposed for use in value-assigning DNA reference materials.
PMID- 26438479
TI - IL-1beta promotes ADAMTS enzyme-mediated aggrecan degradation through NF-kappaB
in human intervertebral disc.
AB - BACKGROUND: The purpose of this study is to investigate IL-1beta regulation of a
disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4 and ADAMTS
5) expression through nuclear factor kappa B (NF-kappaB) in human nucleus
pulposus (NP) cells. METHODS: qRT-PCR and Western blot were used to measure
ADAMTS expression. Transfections and gene silencing were used to determine the
role of NF-kappaB on cytokine-mediated ADAMTS expression and its role in aggrecan
degradation. RESULTS: IL-1beta increased ADAMTS expression in NP cells. Treatment
with NF-kappaB inhibitors abolished the inductive effect of the cytokines on
ADAMTS expression. Silencing of p65 confirmed their role in IL-1beta-dependent
ADAMTS-4 and ADAMTS-5 expression and aggrecan degradation. CONCLUSIONS: By
controlling the activation of NF-kappaB signaling, IL-1beta modulates the
expression of ADAMTS in NP cells. To our knowledge, this is the first study that
shows the contribution of both ADAMTS-4 and ADAMTS-5 to aggrecan degradation in
human NP cells.
PMID- 26438480
TI - Minimally Invasive Resection of Colorectal Cancer Liver Metastases Leads to an
Earlier Initiation of Chemotherapy Compared to Open Surgery.
AB - INTRODUCTION: Previous studies have shown benefit not only from postoperative
chemotherapy but also from a short interval to initiation of treatment after
resection of primary colorectal cancer. The aim of this study was to determine
difference in timing to postoperative chemotherapy for minimally invasive
resection (MIR) vs. open resection (OR) of colorectal cancer liver metastases
(CRCLM). METHODS: This is a retrospective review of 1:1 matched patients
undergoing MIR (n = 66) and OR (n = 66) for CRCLM at a single institution.
RESULTS: Patients undergoing MIR of CRCLM had significantly shorter length of
hospital stay, fewer major complications, and shorter interval to postoperative
chemotherapy (median 42 vs. 63 days, p < 0.001). Univariable analysis showed that
surgical approach, postoperative complications, blood loss, number of lesions,
and length of stay were associated with timing to chemotherapy. On multivariable
analysis, surgical approach was still associated with timing to chemotherapy, and
postoperative complications resulted in a delay of chemotherapy among patients
who underwent OR but not among those who underwent MIR. In addition, worse
disease-free survival was seen among patients who received postoperative
chemotherapy more than 60 days after surgery. CONCLUSION: By modifying the
deleterious effects of postoperative complications on timing of postoperative
chemotherapy, patients undergoing MIR for CRCLM are treated with chemotherapy
sooner after surgery compared to those undergoing OR.
PMID- 26438481
TI - Intra-gastric Ectopic Splenic Tissue.
AB - A 40-year-old man presented with a 3-year duration of intermittent upper
abdominal pain. Gastroscopy and endoscopic ultrasonography revealed a tumor in
the bottom of the stomach with a homogenous low echogenicity that originated from
the gastric serosa. An abdominal contrast-enhanced computed tomography (CT) scan
showed that a well-marginated ovoid mass was obviously enhanced homogenously in
the arterial period and weakened slightly in the venous period. The diagnosis of
a gastric stromal tumor was made. Laparoscopic resection of the gastric tumor was
subsequently performed. Surprisingly, postoperative pathological examination of
the mass showed the typical structure of a normal splenic tissue. To our
knowledge, ectopic splenic tissue originating from the gastric serosa is reported
for the first time, showing important clinical significance for the
identification of gastric malignant tumors.
PMID- 26438482
TI - Prevention of Postoperative Bile Leak in Partial Cystectomy for Hydatid Liver
Disease: Tricks of the Trade.
AB - BACKGROUND: The presence of postoperative bile leak is the major outcome measure
for the assessment of operative success in partial cystectomy for hydatid liver
disease. However, the optimal operative strategy to reduce the postoperative bile
leak rate is yet to be defined. METHODS: Medical records of patients who
underwent partial cystectomy for hydatid liver disease between January 2013 and
January 2015 were reviewed in this retrospective analysis. All patients were
managed with a specific operative protocol. The primary outcome measure was the
rate of persistent postoperative bile leak. The secondary outcome measures were
the morbidity and mortality rate, and the length of hospital stay. RESULTS:
Twenty-eight patients were included in the study. Only one patient (3.6 %)
developed persistent postoperative bile leak. The overall morbidity and mortality
rate was 17.8 and 0 %, respectively. The median length of hospital stay was 5
days. CONCLUSION: Aggressive preventative surgical measures have led to low
persistent bile leak rates with low morbidity and mortality.
PMID- 26438483
TI - Reply to the Letter to the Editor Regarding Manuscript Entitled: "Feasibility of
Fast-Track Surgery in Gastrectomy for Elderly Patients with Gastric Cancer".
PMID- 26438484
TI - Outcomes Improvement Is Not Continuous Along the Learning Curve for
Pancreaticoduodenectomy at the Hospital Level.
AB - BACKGROUND: Most studies on learning curves for pancreaticoduodenectomy have been
based on single-surgeon series at tertiary academic centers or are inferred
indirectly from volume-outcome relationships. Our aim is to describe mortality
rates associated with cumulative surgical experience among non-teaching
hospitals. STUDY DESIGN: Observational study of a statewide inpatient database.
Analysis included hospitals that began performing pancreaticoduodenectomy between
1996 and 2010, as captured by the California Office of Statewide Health Planning
and Development database. Cases were numbered sequentially within each hospital.
The same sequential series (e.g., first 10 cases, 11th through 20th cases) were
identified across hospitals. The outcome measure was in-hospital mortality.
RESULTS: A total of 1210 cases from 143 non-teaching hospitals were analyzed. The
average age was 63 years old, and the majority of patients were non-Hispanic
white. The median overall mortality rate was 9.75 %. The mortality rate for the
first 10 aggregated cases was 11.3 %. This improved for subsequent cases,
reaching 7.1 % for the 21st-30th cases. However, the mortality rate then
increased, reaching 16.7 % by the 41st-50th cases before falling to 0.0 % by the
61st-70th cases. CONCLUSIONS: Initial improvement in surgical outcomes relative
to cumulative surgical experience is not sustained. It is likely that factors
other than surgical experience affect outcomes, such as less rigorous assessment
of comorbidities or changes in support services. Vigilance regarding outcomes
should be maintained even after initial improvements.
PMID- 26438485
TI - Hepatic Resection Improved the Long-Term Survival of Patients with BCLC Stage B
Hepatocellular Carcinoma: a Letter to Response.
PMID- 26438486
TI - Pain and Mortality Risk in a Cohort of HIV-Infected Persons with Alcohol Use
Disorders.
AB - Pain has been associated with increased risk for mortality in some studies. We
analyzed data from a cohort study [HIV-longitudinal interrelationships of viruses
and ethanol (HIV-LIVE)] of HIV-infected persons with alcohol use disorders
enrolled 2001-2003 to explore whether reporting moderate or greater pain
interference was associated with mortality. The main independent variable was
pain that at least moderately interfered with work based on a single question
from the SF-12. Primary analyses dichotomized at "moderately" or above. Cox
proportional hazards models assessed the association between pain interference
and death adjusting for demographics, substance use, CD4 count, HIV viral load
and co-morbidities. Although significant in unadjusted models (HR = 1.58 (95 % CI
1.03-2.41; p value = 0.04)), after adjusting for confounders, >=moderate pain
interference was not associated with an increased risk of death [aHR = 1.30 (95 %
CI 0.81-2.11, p value = 0.28)]. Among HIV-infected persons with alcohol use
disorders, we did not detect a statistically significant independent association
between pain interference and risk of death after adjustment for potential
confounders.
PMID- 26438487
TI - Accuracy and Acceptability of Oral Fluid HIV Self-Testing in a General Adult
Population in Kenya.
AB - We evaluated performance, accuracy, and acceptability parameters of unsupervised
oral fluid (OF) HIV self-testing (HIVST) in a general population in western
Kenya. In a prospective validation design, we enrolled 240 adults to perform
rapid OF HIVST and compared results to staff administered OF and rapid
fingerstick tests. All reactive, discrepant, and a proportion of negative results
were confirmed with lab ELISA. Twenty participants were video-recorded conducting
self-testing. All participants completed a staff administered survey before and
after HIVST to assess attitudes towards OF HIVST acceptability. HIV prevalence
was 14.6 %. Thirty-six of the 239 HIVSTs were invalid (15.1 %; 95 % CI 11.1-20.1
%), with males twice as likely to have invalid results as females. HIVST
sensitivity was 89.7 % (95 % CI 73-98 %) and specificity was 98 % (95 % CI 89-99
%). Although sensitivity was somewhat lower than expected, there is clear
interest in, and high acceptability (94 %) of OF HIV self-testing.
PMID- 26438488
TI - Molecular Cloning and Biochemical Characterization of the Iron Superoxide
Dismutase from the Cyanobacterium Nostoc punctiforme ATCC 29133 and Its Response
to Methyl Viologen-Induced Oxidative Stress.
AB - Superoxide dismutase (SOD) detoxifies cell-toxic superoxide radicals and
constitutes an important component of antioxidant machinery in aerobic organisms,
including cyanobacteria. The iron-containing SOD (SodB) is one of the most
abundant soluble proteins in the cytosol of the nitrogen-fixing cyanobacterium
Nostoc punctiforme ATCC 29133, and therefore, we investigated its biochemical
properties and response to oxidative stress. The putative SodB-encoding open
reading frame Npun_R6491 was cloned and overexpressed in Escherichia coli as a C
terminally hexahistidine-tagged protein. The purified recombinant protein had a
SodB specific activity of 2560 +/- 48 U/mg protein at pH 7.8 and was highly
thermostable. The presence of a characteristic iron absorption peak at 350 nm,
and its sensitivity to H2O2 and azide, confirmed that the SodB is an iron
containing SOD. Transcript level of SodB in nitrogen-fixing cultures of N.
punctiforme decreased considerably (threefold) after exposure to an oxidative
stress-generating herbicide methyl viologen for 4 h. Furthermore, in-gel SOD
activity analysis of such cultures grown at increasing concentrations of methyl
viologen also showed a loss of SodB activity. These results suggest that SodB is
not the primary scavenger of superoxide radicals induced by methyl viologen in N.
punctiforme.
PMID- 26438489
TI - Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing
Isavuconazole, Posaconazole, and Amphotericin B against Molecularly Identified
Mucorales Species.
AB - We compared EUCAST and CLSI antifungal susceptibility testing (AFST) methods for
triazoles and amphotericin B against 124 clinical Mucorales isolates. The EUCAST
method yielded MIC values 1- to 3-fold dilutions higher than those of the CLSI
method for amphotericin B. The essential agreements between the two methods for
triazoles were high, i.e., 99.1% (voriconazole), 98.3% (isavuconazole), and 87%
(posaconazole), whereas it was significantly lower for amphotericin B (66.1%).
Strategies for harmonization of the two methods for Mucorales AFST are warranted.
PMID- 26438490
TI - Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy.
AB - Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan
synthase encoded by FKS genes is the target of echinocandins. A few missense
mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We
report here the rapid emergence of antifungal resistance in C. lusitaniae
isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles
for treatment of persistent candidemia in an immunocompromised child with severe
enterocolitis and visceral adenoviral disease. As documented from restriction
fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD)
analysis, the five C. lusitaniae isolates examined were related to each other.
From antifungal susceptibility and molecular analyses, 5 different profiles (P)
were obtained. These profiles included the following: profile 1 (P1) (CAS MIC
[MUg/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was
being treated with liposomal AMB for 3 months; P2 (FLC MIC [MUg/ml], 0.25; CAS
MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC
[MUg/ml], 0.5; FLC MIC, 32), while the patient was being treated with azoles and
CAS initially followed by azoles alone for a week; P4 (CAS MIC [MUg/ml], 8; FLC
MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5
(AMB MIC [MUg/ml], 0.125; CAS MIC, 8), while the patient was being treated with
AMB and FLC for 2 weeks. CAS resistance was associated with resistance not only
to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance
revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y in P2; S631Y in
P4; S638P in P5). While S638Y and -P are within HS1, S631Y is in close proximity
to this domain but was confirmed to confer candin resistance using a site
directed mutagenesis approach. FLC resistance could be linked with overexpression
of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated
with resistance to 5-flurocytosine. This clinical report describes resistance of
C. lusitaniae to all common antifungals. While candins or azole resistance
followed monotherapy, multidrug antifungal resistance emerged during combined
therapy.
PMID- 26438491
TI - Roflumilast, a Type 4 Phosphodiesterase Inhibitor, Shows Promising Adjunctive,
Host-Directed Therapeutic Activity in a Mouse Model of Tuberculosis.
AB - With phosphodiesterase inhibitors (PDE-Is) showing significant promise in
shortening tuberculosis treatment, we assessed the effect of roflumilast, an FDA
approved type 4 PDE-I, in both acute and chronic murine models of tuberculosis.
Alone, roflumilast had no effect on lung bacillary burden and mortality. However,
when roflumilast was used in combination with isoniazid, a reduction in lung
bacillary burden was observed. These data suggest that roflumilast may be a good
candidate for tuberculosis host-directed therapy (HDT).
PMID- 26438492
TI - Clonal Dissemination of Enterobacter cloacae Harboring blaKPC-3 in the Upper
Midwestern United States.
AB - Carbapenemase-producing, carbapenem-resistant Enterobacteriaceae, or CP-CRE, are
an emerging threat to human and animal health, because they are resistant to many
of the last-line antimicrobials available for disease treatment. Carbapenemase
producing Enterobacter cloacae harboring blaKPC-3 recently was reported in the
upper midwestern United States and implicated in a hospital outbreak in Fargo,
North Dakota (L. M. Kiedrowski, D. M. Guerrero, F. Perez, R. A. Viau, L. J.
Rojas, M. F. Mojica, S. D. Rudin, A. M. Hujer, S. H. Marshall, and R. A. Bonomo,
Emerg Infect Dis 20:1583-1585, 2014, http://dx.doi.org/10.3201/eid2009.140344).
In early 2009, the Minnesota Department of Health began collecting and screening
CP-CRE from patients throughout Minnesota. Here, we analyzed a retrospective
group of CP-E. cloacae isolates (n = 34) collected between 2009 and 2013. Whole
genome sequencing and analysis revealed that 32 of the strains were clonal,
belonging to the ST171 clonal complex and differing collectively by 211 single
nucleotide polymorphisms, and it revealed a dynamic clone under positive
selection. The phylogeography of these strains suggests that this clone existed
in eastern North Dakota and western Minnesota prior to 2009 and subsequently was
identified in the Minneapolis and St. Paul metropolitan area. All strains
harbored identical IncFIA-like plasmids conferring a CP-CRE phenotype and an
additional IncX3 plasmid. In a single patient with multiple isolates submitted
over several months, we found evidence that these plasmids had transferred from
the E. cloacae clone to an Escherichia coli ST131 bacterium, rendering it as a CP
CRE. The spread of this clone throughout the upper midwestern United States is
unprecedented for E. cloacae and highlights the importance of continued
surveillance to identify such threats to human health.
PMID- 26438493
TI - Esters of Pyrazinoic Acid Are Active against Pyrazinamide-Resistant Strains of
Mycobacterium tuberculosis and Other Naturally Resistant Mycobacteria In Vitro
and Ex Vivo within Macrophages.
AB - Pyrazinamide (PZA) is active against major Mycobacterium tuberculosis species (M.
tuberculosis, M. africanum, and M. microti) but not against M. bovis and M.
avium. The latter two are mycobacterial species involved in human and cattle
tuberculosis and in HIV coinfections, respectively. PZA is a first-line agent for
the treatment of human tuberculosis and requires activation by a mycobacterial
pyrazinamidase to form the active metabolite pyrazinoic acid (POA). As a result
of this mechanism, resistance to PZA, as is often found in tuberculosis patients,
is caused by point mutations in pyrazinamidase. In previous work, we have shown
that POA esters and amides synthesized in our laboratory were stable in plasma
(M. F. Simoes, E. Valente, M. J. Gomez, E. Anes, and L. Constantino, Eur J Pharm
Sci 37:257-263, 2009, http://dx.doi.org/10.1016/j.ejps.2009.02.012). Although the
amides did not present significant activity, the esters were active against
sensitive mycobacteria at concentrations 5- to 10-fold lower than those of PZA.
Here, we report that these POA derivatives possess antibacterial efficacy in
vitro and ex vivo against several species and strains of Mycobacterium with
natural or acquired resistance to PZA, including M. bovis and M. avium. Our
results indicate that the resistance probably was overcome by cleavage of the
prodrugs into POA and a long-chain alcohol. Although it is not possible to rule
out that the esters have intrinsic activity per se, we bring evidence here that
long-chain fatty alcohols possess a significant antimycobacterial effect against
PZA-resistant species and strains and are not mere inactive promoieties. These
findings may lead to candidate dual drugs having enhanced activity against both
PZA-susceptible and PZA-resistant isolates and being suitable for clinical
development.
PMID- 26438494
TI - In Vitro Activity of Isavuconazole and Comparators against Clinical Isolates of
the Mucorales Order.
AB - The in vitro activity of isavuconazole against Mucorales isolates measured by
EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison
with those of amphotericin B, posaconazole, and voriconazole. Seventy-two
isolates were included: 12 of Lichtheimia corymbifera, 5 of Lichtheimia ramosa, 5
of group I and 9 of group II of Mucor circinelloides, 9 of Rhizomucor pusillus,
26 of Rhizopus microsporus, and 6 of Rhizopus oryzae. Species identification was
confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read
on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2
(CLSI-d2). Isavuconazole MIC50s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and
EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively,
across all isolates. The similar values for comparator drugs were as follows:
posaconazole, 0.25 (<= 0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16);
amphotericin, 0.06 (<= 0.03 to 0.5), 0.06 (<= 0.03 to 0.25), and 0.125 (<= 0.03
to 1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16),
respectively. Isavuconazole activity varied by species: Lichtheimia corymbifera,
1 (0.5 to 2), 1 (1 to 2), and 2 (1 to 4); Lichtheimia ramosa, 0.25 (0.125 to
0.5), 1 (0.5 to 2), and 2 (0.5 to 4); Rhizomucor pusillus, 0.5 (0.5 to 1), 1
(0.125 to 1), and 2 (1 to 2); Rhizopus microsporus, 1 (0.5 to 4), 0.5 (0.125 to
1), and 4 (1 to 8); and Rhizopus oryzae, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5
to 8), respectively, were more susceptible than Mucor circinelloides: group I, 8
(4 to 8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16),
8 (1 to 8), and 16 (4 to >16), respectively. This was also observed for
posaconazole. The essential agreement was best between EUCAST-d1 and CLSI-d2 (75%
to 83%). Isavuconazole displayed in vitro activity against Mucorales isolates
with the exception of Mucor circinelloides. The MICs were in general 1 to 3 steps
higher than those for posaconazole. However, in the clinical setting this may be
compensated for by the higher exposure at standard dosing.
PMID- 26438496
TI - 3-Halo Chloroquine Derivatives Overcome Plasmodium falciparum Chloroquine
Resistance Transporter-Mediated Drug Resistance in P. falciparum.
AB - Polymorphism in the Plasmodium falciparum chloroquine resistance transporter
(PfCRT) was shown to cause chloroquine resistance. In this report, we examined
the antimalarial potential of novel 3-halo chloroquine derivatives (3-chloro, 3
bromo, and 3-iodo) against chloroquine-susceptible and -resistant P. falciparum.
All three derivatives inhibited the proliferation of P. falciparum; with 3-iodo
chloroquine being most effective. Moreover, 3-iodo chloroquine was highly
effective at potentiating and reversing chloroquine toxicity of drug-susceptible
and -resistant P. falciparum.
PMID- 26438495
TI - Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody
for the Treatment of Respiratory Syncytial Virus Infection.
AB - Respiratory syncytial virus (RSV) is an important causative agent of lower
respiratory tract infections in infants and elderly individuals. Its fusion (F)
protein is critical for virus infection. It is targeted by several
investigational antivirals and by palivizumab, a humanized monoclonal antibody
used prophylactically in infants considered at high risk of severe RSV disease.
ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F protein
with subnanomolar affinity. ALX-0171 demonstrated in vitro neutralization
superior to that of palivizumab against prototypic RSV subtype A and B strains.
Moreover, ALX-0171 completely blocked replication to below the limit of detection
for 87% of the viruses tested, whereas palivizumab did so for 18% of the viruses
tested at a fixed concentration. Importantly, ALX-0171 was highly effective in
reducing both nasal and lung RSV titers when delivered prophylactically or
therapeutically directly to the lungs of cotton rats. ALX-0171 represents a
potent novel antiviral compound with significant potential to treat RSV-mediated
disease.
PMID- 26438497
TI - Susceptibility Pattern of Microorganisms Isolated by Percutaneous Needle Biopsy
in Nonbacteremic Pyogenic Vertebral Osteomyelitis.
AB - Pyogenic vertebral osteomyelitis (VO) is diagnosed according to several lines of
evidence: clinical, biological, radiological, and histological. Definitive
diagnosis requires the isolation of a causative pathogen or histological
confirmation. The aim of our study was to describe the microorganisms isolated by
percutaneous needle biopsy (PNB) and to analyze their susceptibility patterns, in
order to assess the possibility of empirical combination therapy for the
treatment of nonbacteremic patients without resorting to PNB. Based on a French
prospective multicenter study of 351 patients with VO, we compiled clinical,
biological, and radiological findings for 101 patients with microbiologically
confirmed VO. Based on antibiotic susceptibility testing of PNB isolated
pathogens, the suitabilities of four antibiotic combinations were analyzed:
ofloxacin plus rifampin, levofloxacin plus rifampin, ciprofloxacin plus
clindamycin, and ciprofloxacin plus amoxicillin-clavulanate. The main causative
pathogens identified were coagulase-negative Staphylococcus spp. (26% of
isolates), followed by Staphylococcus aureus (21%), Streptoccocus spp. (13%), and
enterobacteria (21%). Empirical antibiotic combination therapy was effective in
nearly 75% of cases, and the different combinations gave similar results, except
for ofloxacin-rifampin, which was effective in only 58% of cases. A "perfect"
empirical antibiotic therapy does not exist. If PNB is not possible, a
combination of a fluoroquinolone with clindamycin or rifampin can be used, but
the high risk of microbiological failure does not allow the exclusion of PNB.
(This study has been registered with EudraCT, number 2006-000951-18, and
ClinicalTrials.gov, number NCT00764114.).
PMID- 26438498
TI - Complex Regulation Pathways of AmpC-Mediated beta-Lactam Resistance in
Enterobacter cloacae Complex.
AB - Enterobacter cloacae complex (ECC), an opportunistic pathogen causing numerous
infections in hospitalized patients worldwide, is able to resist beta-lactams
mainly by producing the AmpC beta-lactamase enzyme. AmpC expression is highly
inducible in the presence of some beta-lactams, but the underlying genetic
regulation, which is intricately linked to peptidoglycan recycling, is still
poorly understood. In this study, we constructed different mutant strains that
were affected in genes encoding enzymes suspected to be involved in this pathway.
As expected, the inactivation of ampC, ampR (which encodes the regulator protein
of ampC), and ampG (encoding a permease) abolished beta-lactam resistance.
Reverse transcription-quantitative PCR (qRT-PCR) experiments combined with
phenotypic studies showed that cefotaxime (at high concentrations) and cefoxitin
induced the expression of ampC in different ways: one involving NagZ (a N-acetyl
beta-D-glucosaminidase) and another independent of NagZ. Unlike the model
established for Pseudomonas aeruginosa, inactivation of DacB (also known as PBP4)
was not responsible for a constitutive ampC overexpression in ECC, whereas it
caused AmpC-mediated high-level beta-lactam resistance, suggesting a post
transcriptional regulation mechanism. Global transcriptomic analysis by
transcriptome sequencing (RNA-seq) of a dacB deletion mutant confirmed these
results. Lastly, analysis of 37 ECC clinical isolates showed that amino acid
changes in the AmpD sequence were likely the most crucial event involved in the
development of high-level beta-lactam resistance in vivo as opposed to P.
aeruginosa where dacB mutations have been commonly found. These findings bring
new elements for a better understanding of beta-lactam resistance in ECC, which
is essential for the identification of novel potential drug targets.
PMID- 26438499
TI - Increased Hydrolysis of Oximino-beta-Lactams by CMY-107, a Tyr199Cys Mutant Form
of CMY-2 Produced by Escherichia coli.
AB - The cephalosporinase CMY-107, a Tyr199Cys mutant form of CMY-2 encoded by an IncI
self-transferable plasmid carried by an Escherichia coli clinical strain, was
characterized. The enzyme hydrolyzed oximino-cephalosporins and aztreonam more
efficiently than CMY-2 did.
PMID- 26438500
TI - Multiple Genetic Mutations Associated with Polymyxin Resistance in Acinetobacter
baumannii.
AB - We studied polymyxin B resistance in 10 pairs of clinical Acinetobacter baumannii
isolates, two of which had developed polymyxin B resistance in vivo. All
polymyxin B-resistant isolates had lower growth rates than and substitution
mutations in the lpx or pmrB gene compared to their parent isolates. There were
significant differences in terms of antibiotic susceptibility and genetic
determinants of resistance in A. baumannii isolates that had developed polymyxin
B resistance in vivo compared to isolates that had developed polymyxin B
resistance in vitro.
PMID- 26438501
TI - Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in
Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse
Transcriptase.
AB - Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in
reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but
adherence to the PrEP regimen is needed. To improve adherence, a long-acting
injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor
rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP
may select for drug-resistant mutations during preexisting or breakthrough
infections, which could promote the spread of drug resistance and limit options
for antiretroviral therapy. To address this concern, we administered RPV LA to
macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT
SHIV). Peak plasma RPV levels were equivalent to those reported in human trials
and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma
viremia, and the therapeutic effect was maintained for 15 weeks, until plasma
drug concentrations dropped below 25 ng/ml. RT mutations E138G and E138Q were
detected in single clones from plasma virus in separate animals only at one time
point, and no resistance mutations were detected in viral RNA isolated from
tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in
vitro, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of
RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged
exposure to slowly decreasing RPV concentrations following injection of RPV LA.
PMID- 26438502
TI - Pharmacodynamic Profiling of a Siderophore-Conjugated Monocarbam in Pseudomonas
aeruginosa: Assessing the Risk for Resistance and Attenuated Efficacy.
AB - The objective of this study was to investigate the risk of attenuated efficacy
due to adaptive resistance for the siderophore-conjugated monocarbam SMC-3176 in
Pseudomonas aeruginosa by using a pharmacokinetic/pharmacodynamic (PK/PD)
approach. MICs were determined in cation-adjusted Mueller-Hinton broth (MHB) and
in Chelex-treated, dialyzed MHB (CDMHB). Spontaneous resistance was assessed at
2* to 16* the MIC and the resulting mutants sequenced. Efficacy was evaluated in
a neutropenic mouse thigh model at 3.13 to 400 mg/kg of body weight every 3 h for
24 h and analyzed for association with free time above the MIC (fT>MIC). To
closer emulate the conditions of the in vivo model, we developed a novel assay
testing activity mouse whole blood (WB). All mutations were found in genes
related to iron uptake: piuA, piuC, pirR, fecI, and pvdS. Against four P.
aeruginosa isolates, SMC-3176 displayed predictable efficacy corresponding to the
fT>MIC using the MIC in CDMHB (R(2) = 0.968 to 0.985), with stasis to 2-log kill
achieved at 59.4 to 81.1%. Efficacy did not translate for P. aeruginosa isolate
JJ 4-36, as the in vivo responses were inconsistent with fT>MIC exposures and
implied a threshold concentration that was greater than the MIC. The results of
the mouse WB assay indicated that efficacy was not predictable using the MIC for
JJ 4-36 and four additional isolates, against which in vivo failures of another
siderophore-conjugated beta-lactam were previously reported. SMC-3176 carries a
risk of attenuated efficacy in P. aeruginosa due to rapid adaptive resistance
preventing entry via the siderophore-mediated iron uptake systems. Substantial in
vivo testing is warranted for compounds using the siderophore approach to
thoroughly screen for this in vitro-in vivo disconnect in P. aeruginosa.
PMID- 26438503
TI - Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2
Diabetes Mellitus: Association with Biochemical and Immunological Parameters.
AB - Tuberculosis (TB) remains a major public health issue due to the increasing
incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical
course of TB and increases the risk of poor long-term outcomes. The aim of this
study was to characterize the pharmacokinetics of rifampin (RIF) and its
relationship with biochemical and immunological parameters in patients with TB
and T2DM. The biochemical and immunological parameters were assessed on the same
day that the pharmacokinetic evaluation of RIF was performed. Factors related to
the metabolic syndrome that is characteristic of T2DM patients were not detected
in the TB-T2DM group (where predominant malnutrition was present) or in the TB
group. Percentages of CD8(+) T lymphocytes and NK cells were diminished in the TB
and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-alpha) and
low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF
absorption was observed in the TB and TB-T2DM patients; absorption was poor and
slower in the latter group due to poor glycemic control. RIF clearance was also
slower in the diabetic patients, thereby prolonging the mean residence time of
RIF. There was a significant association between glycemic control, increased TNF
alpha serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients.
These altered metabolic and immune conditions may be factors to be considered in
anti-TB therapy management when TB and T2DM are concurrently present.
PMID- 26438504
TI - Raltegravir Pharmacokinetics in Patients on Asunaprevir-Daclatasvir.
AB - Raltegravir pharmacokinetics was studied in 20 patients included in the ANRS HC30
QUADRIH Study before and after addition of anti-hepatitis C virus (anti-HCV)
quadritherapy, including pegylated-interferon-ribavirin and asunaprevir plus
daclatasvir. Raltegravir pharmacokinetic parameters remained unchanged whether
administered on or off anti-HCV therapy. In addition, concentrations of
raltegravir, asunaprevir, and daclatasvir were not affected by liver cirrhosis.
These data suggest that in human immunodeficiency virus (HIV)-HCV-coinfected
patients, whether cirrhotic or not, asunaprevir and daclatasvir could be
administered safely with raltegravir.
PMID- 26438505
TI - Validation and Application of a Dried Blood Spot Ceftriaxone Assay.
AB - Dried blood spot (DBS) antibiotic assays can facilitate
pharmacokinetic/pharmacodynamic (PK/PD) studies in situations where venous blood
sampling is logistically and/or ethically problematic. In this study, we aimed to
develop, validate, and apply a DBS ceftriaxone assay. A liquid chromatography
tandem mass spectroscopy (LC-MS/MS) DBS ceftriaxone assay was assessed for matrix
effects, process efficiency, recovery, variability, and limits of quantification
(LOQ) and detection (LOD). The effects of hematocrit, protein binding, red cell
partitioning, and chad positioning were evaluated, and thermal stability was
assessed. Plasma, DBS, and cell pellet ceftriaxone concentrations in 10 healthy
adults were compared, and plasma concentration-time profiles of DBS and plasma
ceftriaxone were incorporated into population PK models. The LOQ and LOD for
ceftriaxone in DBS were 0.14 mg/liter and 0.05 mg/liter, respectively. Adjusting
for hematocrit, red cell partitioning, and relative recovery, DBS-predicted
plasma concentrations were comparable to measured plasma concentrations (r >
0.95, P < 0.0001), and Bland-Altman plots showed no significant bias. The final
population PK estimates of clearance, volume of distribution, and time above
threshold MICs for measured and DBS-predicted plasma concentrations were similar.
At 35 degrees C, 21 degrees C, 4 degrees C, -20 degrees C, and -80 degrees C,
ceftriaxone retained >95% initial concentrations in DBS for 14 h, 35 h, 30 days,
21 weeks, and >11 months, respectively. The present DBS ceftriaxone assay is
robust and can be used as a surrogate for plasma concentrations to provide valid
PK and PK/PD data in a variety of clinical situations, including in studies of
young children and of those in remote or resource-poor settings.
PMID- 26438506
TI - Parenteral Administration of Capsule Depolymerase EnvD Prevents Lethal Inhalation
Anthrax Infection.
AB - Left untreated, inhalation anthrax is usually fatal. Vegetative forms of Bacillus
anthracis survive in blood and tissues during infection due to elaboration of a
protective poly-gamma-D-glutamic acid (PDGA) capsule that permits uncontrolled
bacterial growth in vivo, eventually leading to overwhelming bacillosis and
death. As a measure to counter threats from multidrug-resistant strains, we are
evaluating the prophylactic and therapeutic potential of the PDGA depolymerase
EnvD, a stable and potent enzyme which rapidly and selectively removes the
capsule from the surface of vegetative cells. Repeated intravenous administration
of 10 mg/kg recombinant EnvD (rEnvD) to mice infected with lethal doses of B.
anthracis Ames spores by inhalation prevented the emergence of symptoms of
anthrax and death; all animals survived the 5-day treatment period, and 70%
survived to the end of the 14-day observation period. In contrast to results in
sham-treated animals, the lungs and spleen of rEnvD-dosed animals were free of
gross pathological changes. We conclude that rEnvD has potential as an agent to
prevent the emergence of inhalation anthrax in infected animals and is likely to
be effective against drug-resistant forms of the pathogen.
PMID- 26438507
TI - Effect of temporal stimulus properties on the nociceptive detection probability
using intra-epidermal electrical stimulation.
AB - Chronic pain disorders can be initiated and maintained by malfunctioning of one
or several mechanisms underlying the nociceptive function. Although several
quantitative sensory testing methods exist to characterize the nociceptive
function, it remains difficult to distinguish the contributions of individual
mechanisms. Intra-epidermal electrical stimulation of nociceptive fibers allows
defining stimuli with temporal properties within the timescale of these
mechanisms. Here, we studied the effect of stimulus properties on the
psychophysical detection probability. A psychophysical detection experiment was
conducted including 30 healthy human participants. Participants were presented
with electrical stimuli having various temporal properties. The pulse-width was
varied for single pulse stimuli (either 420 or 840 MUs), and the inter-pulse
interval for double pulse stimuli (10, 50, or 100 ms). Generalized linear mixed
models were used to obtain estimates of thresholds and slopes of the
psychophysical function. The 840-MUs single pulse resulted in a lower threshold
and steeper slope of the psychophysical function than the 420-MUs single pulse.
Moreover, a double-pulse stimulus resulted in a lower threshold and steeper slope
than single pulse stimuli. The slopes were similar between the double pulse
stimuli, but thresholds slightly increased with increasing inter-pulse intervals.
In the present study, it was demonstrated that varying the temporal properties of
intra-epidermal electrical stimuli results in variations in nociceptive
processing. The estimated thresholds and slopes corresponding to the selection of
temporal properties suggest that contributions of peripheral and central
nociceptive mechanisms can be reflected in psychophysical functions.
PMID- 26438508
TI - Testing the concurrent validity of a naturalistic upper extremity reaching task.
AB - Point-to-point reaching has been widely used to study upper extremity motor
control. We have been developing a naturalistic reaching task that adds tool
manipulation and object transport to this established paradigm. The purpose of
this study was to determine the concurrent validity of a naturalistic reaching
task in a sample of healthy adults. This task was compared to the criterion
measure of standard point-to-point reaching. Twenty-eight adults performed
unconstrained out-and-back movements in three different directions relative to
constant start location along midline using their nondominant arm. In the
naturalistic task, participants manipulated a tool to transport objects
sequentially between physical targets anchored to the planar workspace. In the
standard task, participants moved a digital cursor sequentially between virtual
targets, veridical to the planar workspace. In both tasks, the primary measure of
performance was trial time, which indicated the time to complete 15 reaches (five
cycles of three reaches/target). Two other comparator tasks were also designed to
test concurrent validity when components of the naturalistic task were added to
the standard task. Spearman's rank correlation coefficients indicated minimal
relationship between the naturalistic and standard tasks due to differences in
progressive task difficulty. Accounting for this yielded a moderate linear
relationship, indicating concurrent validity. The comparator tasks were also
related to both the standard and naturalistic task. Thus, the principles of motor
control and learning that have been established by the wealth of point-to-point
reaching studies can still be applied to the naturalistic task to a certain
extent.
PMID- 26438510
TI - Concerning the publication: "Histological difference between pulsed wave laser
and continuous wave laser in endovenous laser ablation" by Kansaku R, Sakakibara
N, Amano A, Endo H, Shimabukuro T, Sueishi M. Phlebology 2015; 30: 429-434.
PMID- 26438509
TI - Single-cell coding of sensory, spatial and numerical magnitudes in primate
prefrontal, premotor and cingulate motor cortices.
AB - The representation of magnitude information enables humans and animal species
alike to successfully interact with the external environment. However, how
various types of magnitudes are processed by single neurons to guide goal
directed behavior remains elusive. Here, we recorded single-cell activity from
the dorsolateral prefrontal (PFC), dorsal premotor (PMd) and cingulate motor
(CMA) cortices in monkeys discriminating discrete numerical (numerosity),
continuous spatial (line length) and basic sensory (spatial frequency) stimuli.
We found that almost exclusively PFC neurons represented the different magnitude
types during sample presentation and working memory periods. The frequency of
magnitude-selective cells in PMd and CMA did not exceed chance level. The
proportion of PFC neurons selectively tuned to each of the three magnitude types
were comparable. Magnitude coding was mainly dissociated at the single-neuron
level, with individual neurons representing only one of the three tested
magnitude types. Neuronal magnitude discriminability, coding strength and
temporal evolution were comparable between magnitude types encoded by PFC neuron
populations. Our data highlight the importance of PFC neurons in representing
various magnitude categories. Such magnitude representations are based on largely
distributed coding by single neurons that are anatomically intermingled within
the same cortical area.
PMID- 26438512
TI - Minimal amounts of kindlin-3 suffice for basal platelet and leukocyte functions
in mice.
AB - Hematopoietic cells depend on integrin-mediated adhesion and signaling, which is
induced by kindlin-3 and talin-1. To determine whether platelet and
polymorphonuclear neutrophil (PMN) functions require specific thresholds of
kindlin-3, we generated mouse strains expressing 50%, 10%, or 5% of normal
kindlin-3 levels. We report that in contrast to kindlin-3-null mice, which die
perinatally of severe bleeding and leukocyte adhesion deficiency, mice expressing
as little as 5% of kindlin-3 were viable and protected from spontaneous bleeding
and infections. However, platelet adhesion and aggregation were reduced in vitro
and bleeding times extended. Similarly, leukocyte adhesion, extravasation, and
bacterial clearance were diminished. Quantification of protein copy numbers
revealed stoichiometric quantities of kindlin-3 and talin-1 in platelets and
neutrophils, indicating that reduction of kindlin-3 in our mouse strains
progressively impairs the cooperation with talin-1. Our findings show that very
low levels of kindlin-3 enable basal platelet and neutrophil functions, whereas
in stress situations such as injury and infection, platelets and neutrophils
require a maximum of functional integrins that is achieved with high and
stoichiometric quantities of kindlin-3 and talin-1.
PMID- 26438513
TI - ETV3-NCOA2 in indeterminate cell histiocytosis: clonal translocation supports sui
generis.
PMID- 26438511
TI - Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at
diagnosis and relapse.
AB - Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD)
mutation is an aggressive hematologic malignancy with a grave prognosis. To
identify the mutational spectrum associated with relapse, whole-exome sequencing
was performed on 13 matched diagnosis, relapse, and remission trios followed by
targeted sequencing of 299 genes in 67 FLT3-ITD patients. The FLT3-ITD genome has
an average of 13 mutations per sample, similar to other AML subtypes, which is a
low mutation rate compared with that in solid tumors. Recurrent mutations occur
in genes related to DNA methylation, chromatin, histone methylation, myeloid
transcription factors, signaling, adhesion, cohesin complex, and the spliceosome.
Their pattern of mutual exclusivity and cooperation among mutated genes suggests
that these genes have a strong biological relationship. In addition, we
identified mutations in previously unappreciated genes such as MLL3, NSD1, FAT1,
FAT4, and IDH3B. Mutations in 9 genes were observed in the relapse-specific
phase. DNMT3A mutations are the most stable mutations, and this DNMT3A
transformed clone can be present even in morphologic complete remissions. Of
note, all AML matched trio samples shared at least 1 genomic alteration at
diagnosis and relapse, suggesting common ancestral clones. Two types of clonal
evolution occur at relapse: either the founder clone recurs or a subclone of the
founder clone escapes from induction chemotherapy and expands at relapse by
acquiring new mutations. Relapse-specific mutations displayed an increase in
transversions. Functional assays demonstrated that both MLL3 and FAT1 exert tumor
suppressor activity in the FLT3-ITD subtype. An inhibitor of XPO1 synergized with
standard AML induction chemotherapy to inhibit FLT3-ITD growth. This study
clearly shows that FLT3-ITD AML requires additional driver genetic alterations in
addition to FLT3-ITD alone.
PMID- 26438514
TI - The novel mechanism of lenalidomide activity.
AB - Lenalidomide acts by a novel drug mechanism-modulation of the substrate
specificity of the CRL4(CRBN) E3 ubiquitin ligase. In multiple myeloma,
lenalidomide induces the ubiquitination of IKZF1 and IKZF3 by CRL4(CRBN).
Subsequent proteasomal degradation of these transcription factors kills multiple
myeloma cells. In del(5q) myelodysplastic syndrome, lenalidomide induces the
degradation of CK1alpha, which preferentially affects del(5q) cells because they
express this gene at haploinsufficient levels. In the future, modulation of
ubiquitin ligase function may enable us to target previously "undruggable"
proteins.
PMID- 26438515
TI - The role of iatrogenic foraminal stenosis from lordotic correction in the
development of C5 palsy after posterior laminectomy and fusion.
AB - BACKGROUND: Post-operative C5 nerve root palsy is a known complication following
cervical spine surgery. Although several theories have been proposed, there
remains no consensus as to the etiology of the palsies. Multiple pre-operative
radiographic measures have been assessed for utility in predicting palsy. The
purpose of this study is to evaluate published radiographic parameters as well as
specifically evaluate the effect of cervical lordosis in the development of C5
palsy to establish thresholds that reliably predict the incidence. METHODS: This
study is a retrospective review of 54 consecutive multilevel cervical laminectomy
and fusion surgeries performed by a single spine surgeon between June 2007 and
February 2014. Pre-operative MRI and pre- and post-operative plain films were
assessed to measure anteroposterior diameter (APD) of the spinal cord, cervical
laminar angles, anteroposterior foraminal diameters (FD), cervical curvature
index (Ishihara), cervical spine angle (C2-7), and C4-5 angle. Univariate
analysis through independent t tests was used to compare differences between
groups. Stepwise logistic regression was performed to identify pre-operative
variables associated with C5 palsy. Receiver operating characteristic curves were
created for significant variables to assess predictive accuracy through
determining the area under the curve. RESULTS: There were 13 (24%) palsies in the
54 patients in the study. All palsies completely resolved within 6 months. Among
pre-operative measures, FD and APD were significantly different between the palsy
and non-palsy groups. The average post-operative C4-5 angle was significantly
different between the groups, though the cervical spine angle and curvature
index, as well as the change in these measures from pre-operative measurements,
did not differ significantly between groups. CONCLUSIONS: Post-operative palsy is
likely a result of iatrogenic nerve root compression from a decreased in cross
sectional area of the neuroforamen in a patient with pre-operative narrowing of
the foramen. However, spinal cord drift back may also play a role from the
combined effect of posterior decompression from laminectomy and relative slack
afforded by increased lordosis. Accordingly, increased post-operative lordosis
would increase the likelihood of effect from both of these mechanisms. We
recommended limited conservative lordotic correction in patients with pre
operative foraminal narrowing.
PMID- 26438516
TI - The Unbefriended Patient: An Exercise in Ethical Clinical Reasoning.
PMID- 26438517
TI - Pharmacological identification of cholinergic receptor subtypes on Drosophila
melanogaster larval heart.
AB - The Drosophila melanogaster heart is a popular model in which to study cardiac
physiology and development. Progress has been made in understanding the role of
endogenous compounds in regulating cardiac function in this model. It is well
characterized that common neurotransmitters act on many peripheral and non
neuronal tissues as they flow through the hemolymph of insects. Many of these
neuromodulators, including acetylcholine (ACh), have been shown to act directly
on the D. melanogaster larval heart. ACh is a primary neurotransmitter in the
central nervous system (CNS) of vertebrates and at the neuromuscular junctions on
skeletal and cardiac tissue. In insects, ACh is the primary excitatory
neurotransmitter of sensory neurons and is also prominent in the CNS. A full
understanding regarding the regulation of the Drosophila cardiac physiology by
the cholinergic system remains poorly understood. Here we use semi-intact D.
melanogaster larvae to study the pharmacological profile of cholinergic receptor
subtypes, nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine
receptors (mAChRs), in modulating heart rate (HR). Cholinergic receptor agonists,
nicotine and muscarine both increase HR, while nAChR agonist clothianidin
exhibits no significant effect when exposed to an open preparation at
concentrations as low as 100 nM. In addition, both nAChR and mAChR antagonists
increase HR as well but also display capabilities of blocking agonist actions.
These results provide evidence that both of these receptor subtypes display
functional significance in regulating the larval heart's pacemaker activity.
PMID- 26438518
TI - Effect of Milk Powder Supplementation with Different Calcium Contents on Bone
Mineral Density of Postmenopausal Women in Northern China: A Randomized
Controlled Double-Blind Trial.
AB - The objective of this study is to examine the effect of milk powder
supplementation with different calcium contents on bone mineral density (BMD) in
postmenopausal Chinese women, and to determine a more appropriate dose of calcium
supplementation. A 2-year, randomized controlled double-blind trial.
Postmenopausal women (n = 210) aged 50-65 years were recruited and assigned
randomly into three calcium supplementation groups. All participants received
milk powder supplementation with different calcium contents (300, 600, and 900 mg
per day for groups A, B, and C, respectively) and all groups received 800 IU of
vitamin D per day. During the follow-up period, BMD of the left hip and lumbar
spine (as the main indicator) was measured using dual-energy X-ray absorptiometry
at the baseline, 1 and 2 years. Both three BMD measures and the changes of BMD
over 2 years were used to analyze. Before adjusting for covariates, BMD in group
A of the lumbar spine and groups A and B of greater trochanter decreased
significantly from the baseline over time but increased significantly in the rest
groups of the lumbar spine and greater trochanter and in three groups of Ward's
triangle. There were significant differences across the three groups for changes
of BMD in the greater trochanter and Ward's triangle. When adjusting for
covariates, there were significant decreases with time in group A of the spine (P
= 0.001), groups A and B of greater trochanter (P = 0.0002 and P = 0.04,
respectively) and increases in groups B and C of Ward's triangle (P = 0.03 and P
= 0.004, respectively). BMD change in the greater trochanter was significantly
different among three groups. For healthy postmenopausal women, high calcium milk
powder supplementation was better in retarding bone loss than medium and low
calcium in the greater trochanter. Considering the dietary calcium intake of
postmenopausal women in north of China, a dose of 900 mg/day is considered as the
most appropriate calcium supplementation for greater trochanter but not for other
sites.
PMID- 26438519
TI - NICE referral guidelines for suspected cancer: colorectal cancer and faecal
occult blood testing.
PMID- 26438520
TI - Serum and plasma 5-hydroxyindoleacetic acid as an alternative to 24-h urine 5
hydroxyindoleacetic acid measurement.
AB - BACKGROUND: Neuroendocrine tumours are slow growing tumours known to secrete a
variety of vasoactive peptides which give rise to symptoms of the carcinoid
syndrome. The diagnosis and monitoring of patients with neuroendocrine tumours is
undertaken in many centres using 24 h urinary measurement of 5
hydroxyindoleacetic acid. However, 5-hydroxyindoleacetic acid can also be
quantified in plasma and serum. METHODS: We measured 5-hydroxyindoleacetic acid
concentration in 134 paired EDTA plasma and urine samples from 108 patients with
known neuroendocrine tumours and 26 healthy volunteers. We also compared 5
hydroxyindoleacetic acid concentrations in paired serum and plasma samples (n =
63), then analysed paired urine and serum samples (n = 97). Furthermore, we
examined the impact of renal impairment on serum 5-hydroxyindoleacetic acid by
analysing 5-hydroxyindoleacetic acid in patients without neuroendocrine tumours
in different stages of chronic kidney disease, as indicated by the estimated
glomerular filtration rate. RESULTS: Plasma and urine 5-hydroxyindoleacetic acid
had very similar diagnostic sensitivities and specificities, with areas under the
curve on ROC analysis of 0.917 and 0.920, respectively. Serum and plasma 5
hydroxyindoleacetic acid values showed good correlation but serum results
demonstrated a positive bias, indicating the necessity for different serum and
plasma reference intervals. There was an inverse correlation between estimated
glomerular filtration rate and serum 5-hydroxyindoleacetic acid concentration,
with 5-hydroxyindoleacetic acid increasing once the estimated glomerular
filtration rate falls below 60 mL/min/1.73 m(2). CONCLUSION: The measurement of
both serum and plasma 5-hydroxyindoleacetic acid can be used for the diagnosis
and monitoring of patients with neuroendocrine tumours. Provided renal function
is taken into consideration, either of these tests should be incorporated into
standard practice as an alternative assay to urinary 5-hydroxyindoleacetic acid.
PMID- 26438521
TI - A nicer approach to the use of 'faecal occult blood tests' in assessment of the
symptomatic.
PMID- 26438522
TI - Estimating age-specific trends in circulating testosterone and sex hormone
binding globulin in males and females across the lifespan.
AB - BACKGROUND: Age-specific trends of serum testosterone and sex hormone-binding
globulin across the full lifespan have not been reported. METHODS: We deduced age
specific trends in serum testosterone and sex hormone-binding globulin in males
and females between ages 10 and 90 from a large sample of consecutive results
from a single large pathology laboratory. Coded results of 110,712 consecutive
blood samples requesting serum testosterone over seven years (2007-2013)
comprising blood testosterone, sex hormone-binding globulin and calculated free
testosterone together with gender and age were analysed create smoothed age
specific centiles (2.5%, 5%, 25%, 50%, 75%, 95%, 97.5%) for males and females.
RESULTS: These identified the pubertal increases in serum testosterone in males
peaking at 20 years of age and remaining stable thereafter until the eighth
decade. In females, circulating testosterone peaked in late adolescence and
declined gradually over the next two decades but remained stable across menopause
and beyond. After early childhood, serum sex hormone-binding globulin declines to
a nadir in males at the age of 20 years and remains stable till the sixth decade
with a gradual, progressive rise thereafter. In females, the sex hormone-binding
globulin nadir is reached earlier with levels rising gradually and progressively
with age thereafter and accelerating after the age of 70 years. Females also
exhibit a second sex hormone-binding globulin peak during reproductive ages
reflected only in upper centiles due to effects of pregnancy and oral
contraceptive use in a significant minority of females. CONCLUSIONS: This large
sample of clinical data provides a comprehensive profile of androgen status
across the lifespan from early adolescence to late old age.
PMID- 26438523
TI - Cellular Dynamics of Memory B Cell Populations: IgM+ and IgG+ Memory B Cells
Persist Indefinitely as Quiescent Cells.
AB - Despite their critical role in long-term immunity, the life span of individual
memory B cells remains poorly defined. Using a tetracycline-regulated pulse-chase
system, we measured population turnover rates and individual t1/2 of pre
established Ag-induced Ig class-switched and IgM-positive memory B cells over 402
d. Our results indicate that, once established, both IgG-positive and less
frequent IgM-positive memory populations are exceptionally stable, with little
evidence of attrition or cellular turnover. Indeed, the vast majority of cells in
both pools exhibited t1/2 that appear to exceed the life span of the mouse,
contrasting dramatically with mature naive B cells. These results indicate that
recall Ab responses are mediated by stable pools of extremely long-lived cells,
and suggest that Ag-experienced B cells employ remarkably efficient survival
mechanisms.
PMID- 26438524
TI - UNC-45A Is a Nonmuscle Myosin IIA Chaperone Required for NK Cell Cytotoxicity via
Control of Lytic Granule Secretion.
AB - NK cell's killing is a tightly regulated process under the control of specific
cytoskeletal proteins. This includes Wiskott-Aldrich syndrome protein, Wiskott
Aldrich syndrome protein-interacting protein, cofilin, Munc13-4, and nonmuscle
myosin IIA (NMIIA). These proteins play a key role in controlling NK-mediated
cytotoxicity either via regulating the attachment of lytic granules to the actin
based cytoskeleton or via promoting the cytoskeletal reorganization that is
requisite for lytic granule release. UNC-45A is a highly conserved member of the
UNC-45/CRO1/She4p family of proteins that act as chaperones for both conventional
and nonconventional myosin. Although we and others have shown that in lower
organisms and in mammalian cells NMIIA-associated functions, such as cytokinesis,
cell motility, and organelle trafficking, are dependent upon the presence of UNC
45A, its role in NK-mediated functions is largely unknown. In this article, we
describe UNC-45A as a key regulator of NK-mediated cell toxicity. Specifically we
show that, in human NK cells, UNC-45A localize at the NK cell immunological
synapse of activated NK cells and is part of the multiprotein complex formed
during NK cell activation. Furthermore, we show that UNC-45A is disposable for NK
cell immunological synapse formation and lytic granules reorientation but crucial
for lytic granule exocytosis. Lastly, loss of UNC-45A leads to reduced NMIIA
binding to actin, suggesting that UNC-45A is a crucial component in regulating
human NK cell cytoskeletal dynamics via promoting the formation of actomyosin
complexes.
PMID- 26438526
TI - NK Cell Functional Impairment after Allogeneic Hematopoietic Stem Cell
Transplantation Is Associated with Reduced Levels of T-bet and Eomesodermin.
AB - NK cells play a major role in protection against tumor recurrence and infection
after allogeneic hematopoietic stem cell transplantation (HSCT). It has been
shown that NK cell function after HSCT is impaired, but underlying molecular
mechanisms are not well-known. In this report we show that the level of T-bet and
Eomesodermin (Eomes), two T-box transcription factors regulating lymphocyte
effector functions, is strongly reduced in NK cells from HSCT recipients compared
with healthy control subjects. Reduction of T-bet and Eomes expression appeared
early and persisted for years after HSCT, affecting all peripheral blood NK cells
independently of their differentiation status. Reduced T-bet levels in NK cells
from allogeneic HSCT recipients significantly correlated with reduced perforin
expression. Acute, but not chronic, graft-versus-host disease, as well as CMV
reactivation, was associated with further downregulation of T-bet expression in
NK cells. Lower levels of T-bet expression in NK cells were associated with less
favorable outcome after HSCT as a result of increased nonrelapse mortality.
Collectively, our results provide a possible molecular explanation for the
previously reported functional exhaustion of NK cells after allogeneic HSCT and
suggest an impact of the NK transcriptional machinery status on HSCT outcome.
PMID- 26438527
TI - Short-term and longer-term survival after veno-arterial extracorporeal membrane
oxygenation in an adult patient population: does older age matter?
AB - BACKGROUND: Veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) is
increasingly being used for patients with refractory cardiopulmonary failure.
This study evaluates the short-term (to discharge) and longer-term (1 year)
survival among older (?65 years) versus younger (<65 years) adults, adjusted for
comorbidities, in a diverse cohort of V-A ECMO patients. METHODS: This was a
retrospective cohort analysis of 131 adult patients (28% ?65 years old) who
received V-A ECMO at an academic medical center from 2004-2013. Demographics,
comorbidities and surgical characteristics were abstracted from the medical
records and verified. Mortality status at discharge and at one year post-ECMO
were determined by the hospital clinical information system, updated monthly with
Social Security Death Index data. Cox proportional hazard analyses were conducted
to evaluate associations between age strata and mortality at discharge and at one
year post ECMO initiation, adjusted for covariates. RESULTS: The survival rate
following V-A ECMO was 48% (n=68/131) to discharge and 44% (n=58/131) to one
year. Age ?65 versus <65 was significantly associated with increased mortality
during hospitalization (HR:2.03; 95%CI=1.23-3.33) and at one year (HR:1.81; 95%
CI=1.12-2.93); these associations were attenuated and did not retain statistical
significance after adjustment for comorbidities (HR:1.61; 95%CI=0.90-2.88 and
HR:1.42; 95% CI=0.81-2.50, respectively). Statistically significant predictors of
mortality at discharge and one year included history of coronary artery bypass
graft, peripheral vascular disease and renal failure/dialysis (p<0.05).
CONCLUSIONS: Older age was not independently associated with short-term or longer
term survival among V-A ECMO patients, but may reflect greater comorbidity,
suggesting that age alone may not disqualify patients from V-A ECMO therapy.
PMID- 26438525
TI - Ptpn22 and Cd2 Variations Are Associated with Altered Protein Expression and
Susceptibility to Type 1 Diabetes in Nonobese Diabetic Mice.
AB - By congenic strain mapping using autoimmune NOD.C57BL/6J congenic mice, we
demonstrated previously that the type 1 diabetes (T1D) protection associated with
the insulin-dependent diabetes (Idd)10 locus on chromosome 3, originally
identified by linkage analysis, was in fact due to three closely linked Idd loci:
Idd10, Idd18.1, and Idd18.3. In this study, we define two additional Idd loci-
Idd18.2 and Idd18.4--within the boundaries of this cluster of disease-associated
genes. Idd18.2 is 1.31 Mb and contains 18 genes, including Ptpn22, which encodes
a phosphatase that negatively regulates T and B cell signaling. The human
ortholog of Ptpn22, PTPN22, is associated with numerous autoimmune diseases,
including T1D. We, therefore, assessed Ptpn22 as a candidate for Idd18.2;
resequencing of the NOD Ptpn22 allele revealed 183 single nucleotide
polymorphisms with the C57BL/6J (B6) allele--6 exonic and 177 intronic.
Functional studies showed higher expression of full-length Ptpn22 RNA and
protein, and decreased TCR signaling in congenic strains with B6-derived Idd18.2
susceptibility alleles. The 953-kb Idd18.4 locus contains eight genes, including
the candidate Cd2. The CD2 pathway is associated with the human autoimmune
disease, multiple sclerosis, and mice with NOD-derived susceptibility alleles at
Idd18.4 have lower CD2 expression on B cells. Furthermore, we observed that
susceptibility alleles at Idd18.2 can mask the protection provided by Idd10/Cd101
or Idd18.1/Vav3 and Idd18.3. In summary, we describe two new T1D loci, Idd18.2
and Idd18.4, candidate genes within each region, and demonstrate the complex
nature of genetic interactions underlying the development of T1D in the NOD mouse
model.
PMID- 26438528
TI - Campaigners demand right to generic version of breast cancer drug.
PMID- 26438530
TI - Higher visit-to-visit intra-dialytic blood pressure is associated with the
progression of aortic valve stenosis in chronic hemodialysis patients.
AB - Aortic valve stenosis (AS) is a frequent complication contributing to poor
prognosis in chronic hemodialysis (CHD) patients. High blood pressure (BP) is
known to be associated with AS progression in the general population. In CHD
patients, however, BP varies during and between hemodialysis sessions with
ultrafiltration volume or inter-dialytic weight gain; therefore it is difficult
to characterize the BP status with a conventional single measurement. Our purpose
was to clarify the BP variables affecting AS progression in CHD patients. We
retrospectively enrolled 32 consecutive CHD patients with AS [aortic valve area
(AVA), 1.3 +/- 0.3 cm(2); mean age 69 +/- 8 years] who had serial transthoracic
echocardiographic studies at least 6 months apart (mean 23 +/- 9 months). AS
progression was evaluated using absolute reduction in AVA per year. Pre-dialytic
and intra-dialytic (every hour during sessions) BPs throughout the 3 consecutive
visits were used to determine each patient's BP status. We calculated the mean
values of pre-dialytic and intra-dialytic BPs and their variability. In
univariate analysis, mean visit-to-visit pre-dialytic and intra-dialytic BP were
associated with AS progression, whereas all variables of BP variability were not.
Multiple regression analysis indicated that only mean visit-to-visit intra
dialytic systolic and diastolic BP remained independently associated with AS
progression after adjustment for age, sex, hypertension, hypercholesterolemia,
diabetes mellitus, and serum parathyroid hormone (p < 0.05). Although BP
regulation in CHD patients is complex and multifactorial, mean visit-to-visit
intra-dialytic BP was independently associated with AS progression. Prospective
studies are necessary before considering intra-dialytic BP as a potential target
for therapy.
PMID- 26438529
TI - Genetics ignite focus on microglial inflammation in Alzheimer's disease.
AB - In the past five years, a series of large-scale genetic studies have revealed
novel risk factors for Alzheimer's disease (AD). Analyses of these risk factors
have focused attention upon the role of immune processes in AD, specifically
microglial function. In this review, we discuss interpretation of genetic
studies. We then focus upon six genes implicated by AD genetics that impact
microglial function: TREM2, CD33, CR1, ABCA7, SHIP1, and APOE. We review the
literature regarding the biological functions of these six proteins and their
putative role in AD pathogenesis. We then present a model for how these factors
may interact to modulate microglial function in AD.
PMID- 26438531
TI - Increased IL18 mRNA levels in peripheral artery disease and its association with
triglyceride and LDL cholesterol levels: a pilot study.
AB - Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia
caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a
pleiotropic pro-inflammatory cytokine reported to function as an inflammatory
biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity
naturally occurring IL18-binding protein (IL18BP). This study aimed to determine
whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was
previously associated with IL18 gene transcriptional activity, were associated
with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear
cells and -137 G/C (rs187238) polymorphism were determined by quantitative real
time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD
patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18
mRNA levels were increased in PAD patients compared with healthy controls (p =
0.09); however, did not reach a statistical significant level, also did not
significantly differ between aorta-iliac and femoro-popliteal occlusive PAD
subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in
PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238
polymorphism did not significantly differ between PAD patients and controls (p =
0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL
cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL
cholesterol levels were negatively correlated with IL18 mRNA levels in controls
(p = 0.05). This report is a preliminary study to show an association between
IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a
significant relationship with triglyceride and LDL cholesterol levels in PAD
patients.
PMID- 26438532
TI - Use and outcome of thrombus aspiration in patients with primary PCI for acute ST
elevation myocardial infarction: results from the multinational Euro Heart Survey
PCI Registry.
AB - The clinical benefit of thrombus aspiration (TA) in patients presenting with
acute ST-elevation myocardial infarction (STEMI) and treated with primary
percutaneous coronary intervention (PCI) is not well defined. Furthermore, there
is a large variation in the use of TA in real-world registries. Between 2005 and
2008, a total of 7146 consecutive patients with acute STEMI undergoing primary
PCI were prospectively enrolled into the PCI Registry of the Euro Heart Survey
Programme. For the present analysis, patients treated additionally with TA (n =
897, 12.6 %) were compared with those without TA (n = 6249, 87.4 %). Patients
with hemodynamic instability at initial presentation (15.1 vs. 11.0 %; p < 0.001)
and resuscitation prior to PCI (10.4 vs. 7.4 %; p = 0.002) were more frequently
treated with TA. TIMI flow grade 0/1 before PCI was more often found among those
with TA (73.5 vs. 58.6 %; p < 0.001). After adjustment for confounding factors in
the propensity score analysis, TA was not associated with improved in-hospital
survival (risk difference -1.1 %, 95 % confidence interval -2.7 to 0.6 %). In
this European real-world registry, the rate of TA use was low. Hemodynamically
unstable patients were more likely to be treated with TA. Consistent with the
results of the TASTE study and the TOTAL trial, TA was not associated with a
significant reduction in short-term mortality.
PMID- 26438533
TI - Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in
humans.
AB - PURPOSE: The purpose of this study is to investigate the pharmacokinetics and
deep tissue penetration capability of the newly developed S-flurbiprofen plaster
(SFPP) in humans. METHODS: Study 1: SFPP tape-type patch (2-60 mg) was applied to
the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma
concentration was measured over time to examine SFP pharmacokinetics. Study 2:
SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA)
patients who were scheduled for total knee arthroplasty. Deep tissues (synovial
tissue and synovial fluid) were collected during surgery to compare SFP
concentrations after application of SFPP or a commercially available flurbiprofen
(FP) gel-type patch. RESULTS: Study 1: The plasma concentration of SFP was
sustained during 24-h topical application of the SFPP, showing a high
percutaneous absorption ratio of 51.4-72.2 %. Cmax and AUC0-infinity were dose
proportional. Study 2: After application of the SFPP for 12 h, SFP concentrations
in the synovial tissue and synovial fluid were 14.8-fold (p = 0.002) and 32.7
fold (p < 0.001) higher, respectively, than those achieved by the FP patch.
CONCLUSIONS: Sustained plasma concentration of SFP and high percutaneous
absorption ratio was observed after 24-h topical application of the SFPP.
Compared to the FP patch, the SFPP showed superior percutaneous absorption and
greater tissue penetration of SFP into the synovial tissue. Greater tissue
penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP
is expected to show higher efficacy for the treatment of knee OA.
PMID- 26438534
TI - Insights into molecular plasticity in protein complexes from Trm9-Trm112 tRNA
modifying enzyme crystal structure.
AB - Most of the factors involved in translation (tRNA, rRNA and proteins) are subject
to post-transcriptional and post-translational modifications, which participate
in the fine-tuning and tight control of ribosome and protein synthesis processes.
In eukaryotes, Trm112 acts as an obligate activating platform for at least four
methyltransferases (MTase) involved in the modification of 18S rRNA (Bud23), tRNA
(Trm9 and Trm11) and translation termination factor eRF1 (Mtq2). Trm112 is then
at a nexus between ribosome synthesis and function. Here, we present a structure
function analysis of the Trm9-Trm112 complex, which is involved in the 5
methoxycarbonylmethyluridine (mcm(5)U) modification of the tRNA anticodon wobble
position and hence promotes translational fidelity. We also compare the known
crystal structures of various Trm112-MTase complexes, highlighting the structural
plasticity allowing Trm112 to interact through a very similar mode with its MTase
partners, although those share less than 20% sequence identity.
PMID- 26438535
TI - Influence of 5-N-carboxamide modifications on the thermodynamic stability of
oligonucleotides.
AB - We have recently shown that the incorporation of modified nucleotides such as 5-N
carboxamide-deoxyuridines into random nucleic acid libraries improves success
rates in SELEX experiments and facilitates the identification of ligands with
slow off-rates. Here we report the impact of these modifications on the
thermodynamic stability of both duplexes and intramolecular 'single-stranded'
structures. Within duplexes, large, hydrophobic naphthyl groups were
destabilizing relative to the all natural DNA duplex, while the hydrophilic
groups exhibited somewhat improved duplex stability. All of the significant
changes in stability were driven by opposing contributions from the enthalpic and
entropic terms. In contrast, both benzyl and naphthyl modifications stabilized
intramolecular single-stranded structures relative to their natural DNA analogs,
consistent with the notion that intramolecular folding allows formation of novel,
stabilizing hydrophobic interactions. Imino proton NMR data provided evidence
that elements of the folded structure form at temperatures well below the Tm,
with a melting transition that is distinctly less cooperative when compared to
duplex DNA. Although there are no data to suggest that the unmodified DNA
sequences fold into structures similar to their modified analogs, this still
represents clear evidence that these modifications impart thermodynamic stability
to the folded structure not achievable with unmodified DNA.
PMID- 26438536
TI - Attomole quantification and global profile of RNA modifications: Epitranscriptome
of human neural stem cells.
AB - Exploration of the epitranscriptome requires the development of highly sensitive
and accurate technologies in order to elucidate the contributions of the more
than 100 RNA modifications to cell processes. A highly sensitive and accurate
ultra-high performance liquid chromatography-tandem mass spectrometry method was
developed to simultaneously detect and quantify 28 modified and four major
nucleosides in less than 20 min. Absolute concentrations were calculated using
extinction coefficients of each of the RNA modifications studied. A comprehensive
RNA modifications database of UV profiles and extinction coefficient is reported
within a 2.3-5.2 % relative standard deviation. Excellent linearity was observed
0.99227-0.99999 and limit of detection values ranged from 63.75 attomoles to 1.21
femtomoles. The analytical performance was evaluated by analyzing RNA
modifications from 100 ng of RNA from human pluripotent stem cell-derived neural
cells. Modifications were detected at concentrations four orders of magnitude
lower than the corresponding parental nucleosides, and as low as 23.01
femtograms, 64.09 attomoles. Direct and global quantitative analysis of RNA
modifications are among the advantages of this new approach.
PMID- 26438537
TI - A novel transcriptional regulator of L-arabinose utilization in human gut
bacteria.
AB - Carbohydrate metabolism plays a crucial role in the ecophysiology of human gut
microbiota. Mechanisms of transcriptional regulation of sugar catabolism in
commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron
remain mostly unknown. By a combination of bioinformatics and experimental
approaches, we have identified an NrtR family transcription factor (BT0354 in B.
thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose
utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR.
We have solved the crystal structures of the apo and L-arabinose-bound BtAraR
proteins, as well as the complex of apo-protein with a specific DNA operator.
BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix
hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain.
We have identified the residues involved in binding of L-arabinose and
recognition of DNA. The majority of these residues are well conserved in the AraR
orthologs in Bacteroidetes. In the structure of the BtAraR-DNA complex, we found
the unique interaction of arginine intercalating its guanidinum moiety into the
base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH
domains, resulting in a conformation unsuitable for DNA binding. Our analysis
facilitates reconstruction of the metabolic and regulatory networks involved in
carbohydrate utilization in human gut Bacteroides.
PMID- 26438538
TI - dbSUPER: a database of super-enhancers in mouse and human genome.
AB - Super-enhancers are clusters of transcriptional enhancers that drive cell-type
specific gene expression and are crucial to cell identity. Many disease
associated sequence variations are enriched in super-enhancer regions of disease
relevant cell types. Thus, super-enhancers can be used as potential biomarkers
for disease diagnosis and therapeutics. Current studies have identified super
enhancers in more than 100 cell types and demonstrated their functional
importance. However, a centralized resource to integrate all these findings is
not currently available. We developed dbSUPER
(http://bioinfo.au.tsinghua.edu.cn/dbsuper/), the first integrated and
interactive database of super-enhancers, with the primary goal of providing a
resource for assistance in further studies related to transcriptional control of
cell identity and disease. dbSUPER provides a responsive and user-friendly web
interface to facilitate efficient and comprehensive search and browsing. The data
can be easily sent to Galaxy instances, GREAT and Cistrome web-servers for
downstream analysis, and can also be visualized in the UCSC genome browser where
custom tracks can be added automatically. The data can be downloaded and exported
in variety of formats. Furthermore, dbSUPER lists genes associated with super
enhancers and also links to external databases such as GeneCards, UniProt and
Entrez. dbSUPER also provides an overlap analysis tool to annotate user-defined
regions. We believe dbSUPER is a valuable resource for the biology and genetic
research communities.
PMID- 26438539
TI - CRISPRz: a database of zebrafish validated sgRNAs.
AB - CRISPRz (http://research.nhgri.nih.gov/CRISPRz/) is a database of CRISPR/Cas9
target sequences that have been experimentally validated in zebrafish.
Programmable RNA-guided CRISPR/Cas9 has recently emerged as a simple and
efficient genome editing method in various cell types and organisms, including
zebrafish. Because the technique is so easy and efficient in zebrafish, the most
valuable asset is no longer a mutated fish (which has distribution challenges),
but rather a CRISPR/Cas9 target sequence to the gene confirmed to have high
mutagenic efficiency. With a highly active CRISPR target, a mutant fish can be
quickly replicated in any genetic background anywhere in the world. However,
sgRNA's vary widely in their activity and models for predicting target activity
are imperfect. Thus, it is very useful to collect in one place validated CRISPR
target sequences with their relative mutagenic activities. A researcher could
then select a target of interest in the database with an expected activity. Here,
we report the development of CRISPRz, a database of validated zebrafish CRISPR
target sites collected from published sources, as well as from our own in-house
large-scale mutagenesis project. CRISPRz can be searched using multiple inputs
such as ZFIN IDs, accession number, UniGene ID, or gene symbols from zebrafish,
human and mouse.
PMID- 26438540
TI - Second primary osteosarcomas in patients with retinoblastoma.
AB - OBJECTIVE: Second primary malignancies have become the leading cause of death in
retinoblastoma survivors. Although osteosarcoma is the most common second
malignancy, little is known about its clinical and therapeutic features. METHODS:
We retrospectively reviewed a database of patients with retinoblastoma and
osteosarcoma occurring as a second malignancy between 1964 and 2010 at the
National Cancer Center Hospital of Japan. RESULTS: Among 857 patients with
retinoblastoma registered in the database, 10 (1.1%) developed osteosarcoma as a
second malignancy. The median age at the onset of retinoblastoma was 3 months,
being bilateral in nine patients and unilateral in one. Systemic chemoreduction
was performed in three patients and intra-arterial chemotherapy in six; all
patients received external beam radiotherapy. The median age at the onset of
second primary osteosarcoma was 11.2 years; four were radiation-related and six
were located in an extremity. Among five patients treated at our institute, four
patients with tumors on an extremity were treated by wide resection with
neoadjuvant and adjuvant chemotherapy. Three of these four patients (75%) were
good responders to high-dose methotrexate-based multi-agent chemotherapy and
survived with no evidence of disease (median follow-up period, 17.3 years). One
patient whose temporal bone was affected underwent radiotherapy with chemotherapy
but died after local recurrence. CONCLUSIONS: The clinical outcomes of second
primary osteosarcoma in an extremity occurring in retinoblastoma survivors may be
more favorable than those of conventional osteosarcoma. Early diagnosis of
radiation-related osteosarcoma arising in the craniofacial region should be made
at a stage where complete resection is possible.
PMID- 26438541
TI - Gait analysis in dogs with pelvic fractures treated conservatively using a
pressure-sensing walkway.
AB - BACKGROUND: This study aimed to evaluate dogs with pelvic fractures and treated
conservatively during locomotion on a pressure-sensing walkway. The hypothesis
was that dogs may present changes in kinetic and temporospatial parameters
because of the fractures, which may interfere with the symmetry index. Thirty
dogs were selected and divided into two groups: Group 1-healthy group (n = 15)
and Group 2-conservatively treated group (n = 15). The dogs were of similar body
size. The body weight distribution percentages and symmetry indices of the peak
vertical force, vertical impulse, stance time, swing time, percentage of stance
time, and percentage of swing time of the hind limbs were evaluated. RESULTS: In
Group 2, the time interval between fracture occurrence and patient evaluation was
between 4 and 87 months (mean of 20 months). Four dogs had lower percentage of
body weight distribution on one of the hind limbs while three dogs had greater
weight distributed toward both hind limbs. Four of these dogs had alterations in
the temporospatial and/or kinetic symmetry indices. CONCLUSIONS: Dogs with pelvic
fractures treated conservatively may present changes in percentage of body weight
distribution and symmetry indices of the kinetic and temporospatial parameters.
The conservative treatment can cause persistent abnormal gait.
PMID- 26438542
TI - America and the age of genocide: labeling a third-party conflict "genocide"
decreases support for intervention among ingroup-glorifying Americans because
they down-regulate guilt and perceived responsibility to intervene.
AB - Drawing on research on the collapse of compassion and group processes and
interrelations, four experiments investigated how labeling a conflict "genocide"
affects distant bystanders' support for intervention. The genocide label
(compared with no label or the label "not a genocide") weakened Americans'
support for intervention in a crisis analogous to Darfur. Ingroup glorification
moderated this effect such that the genocide label decreased support at high
levels of glorification (Studies 1-3). Ingroup attachment, if anything, moderated
such that the genocide label increased support at high levels of attachment
(Studies 1 and 3). Importantly, the effects occurred even when controlling for
conservatism (Studies 1 and 3), gender, religion, military affiliation, and level
of education (Study 2). Decreases in anticipated guilt over possible
nonintervention (Studies 1 and 3) among high glorifiers, and a subsequent
decrease in perceived obligation to intervene (Study 3), mediated the effect of
the genocide label on support for intervention.
PMID- 26438543
TI - Urologist is investigated by GMC after review by Royal College of Surgeons.
PMID- 26438544
TI - Embryonal tumors with multilayered rosettes in children: the SFCE experience.
AB - PURPOSES: The purpose of this study was to retrospectively study embryonal tumors
with multilayered rosettes (ETMR), a rare new entity that gathers ETAN-TR
(embryonal tumor with abundant neuropil and true rosettes), ependymoblastomas,
and medulloepitheliomas, in order to improve their descriptions and try to better
define therapeutic modalities. METHODS: Patients with ETMR, ETAN-TR,
ependymoblastoma, and medulloepithelioma treated in SFCE centres (Societe
Francaise de lutte contre les Cancers et les leucemies de l'Enfant et de
l'adolescent) since 2000 were collected. Data were retrieved from clinical
charts. RESULTS: Thirty-eight patients were included in the analysis. Seventeen
had an ETAN-TR, 13 had a medulloepithelioma, and 8 had an ETMR. No
ependymoblastoma was included. The median age at diagnosis was 31 months (range,
2.8-141 months). The predominant tumor location was supratentorial (66%); 18.4%
patients had metastatic lesion. LIN28A expression was positive in 11/11 patients.
Amplification of the locus 19q13.42 was positive in 10/12 patients. Thirty
patients were treated according to the primitive neuroectodermal tumors of high
risk (PNET-HR) protocol. The median time of follow-up was 0.9 years (range 0.1 to
15.3 years). The 1-year event-free survival (EFS) and overall survival (OS) were,
respectively, 36% CI 95% (23-55) and 45% CI 95% (31-64). On multivariate
analysis, complete surgical resection, radiotherapy, and high-dose chemotherapy
were associated with a better overall survival with a relative risk of,
respectively, 7.9 CI 95% (2.6-23.5) p < 0.0002, 41.8 CI 95% (9.4-186) p < 0.0001,
and 3.5 CI 95% (1.3-9.5) p = 0.012. CONCLUSION: Prognosis of ETMR remains dismal
despite multimodal therapy. LIN28A immunostaining and 19q13.42 amplification
should be systematically done to secure the diagnosis. Complete surgical
resection, radiotherapy, and high-dose chemotherapy are associated with better
outcome.
PMID- 26438546
TI - Posture and movement in very preterm infants at term age in and outside the nest.
AB - OBJECTIVE: The objective of this study is to evaluate the use of nests on general
movements (GM) and posture in very preterm infants at term age. METHOD: Seventeen
high-risk preterm infants-less than 30 weeks of gestation (GA)-underwent a video
recording, lying in supine position, with or without nest. Posture, GM quality,
and movements made around the child's midline, as well as abrupt movements and
frozen postures-in extension or flexion of the four limbs-were analyzed. RESULTS:
Nest did not modify quality of GM. Children significantly adopted a curled-up
position. The nest system was associated with an increase in movements toward or
across the midline, as well as reduction of the hyperextension posture and head
rotation movements. Frozen postures in flexion or extension, as well as abrupt
movements of the four limbs, were reduced but not significantly. CONCLUSIONS:
Nest helps very preterm infants to adopt semi-flexed posture and facilitates
movements across the midline and reduces movements of spine hyperextension,
without GM global quality modifications.
PMID- 26438545
TI - Bilateral occlusion of the foramina of Monro after endoscopic third
ventriculostomy for aqueductal stenosis--a case report.
AB - CASE REPORT: Bilateral occlusion of the foramina of Monro is an extremely rare
clinical condition. We present the case of a 10-year-old girl who complained of
frequent headaches. METHODS: Magnetic resonance imaging showed triventricular
hydrocephalus due to aqueductal stenosis, so endoscopic third ventriculostomy was
performed successfully. The headaches subsequently disappeared, but the patient
presented with exacerbation of headaches 32 months postoperatively. Magnetic
resonance imaging demonstrated bilateral hydrocephalus of the lateral ventricles,
implying bilateral occlusion of the foramina of Monro. We again performed
endoscopic surgery, confirming bilateral occlusion of the foramina of Monro.
RESULTS: The foramina of Monro were apparently obstructed by normal ependyma, and
no tumor masses or other structures were detected around the foramina, so we
diagnosed the occlusion of the foramina as secondary after endoscopic third
ventriculostomy. We fenestrated the septum pellucidum using a monopolar micro
endoscopic electrode, and a ventriculoperitoneal shunt was placed for the
management of hydrocephalus. The postoperative course was uneventful, and the
headaches were completely resolved.
PMID- 26438548
TI - Pediatric gliosarcoma treated with adjuvant radiotherapy and temozolomide.
AB - PURPOSE: Primary pediatric gliosarcoma (pPGS) is an extremely rare entity with
only 25 cases reported in the English literature. The value of concurrent and
adjuvant temozolomide is not known in this group of patient. METHODS: Five
patients of pPGS treated from 2006 to 2011 were included in this retrospective
analysis. All patients underwent maximal safe surgical resection. Adjuvant
therapy included conformal radiation 60 Gy in 30 fractions (2 Gy daily for 5 days
in a week) with concurrent temozolomide 75 mg/m(2) daily followed by six cycles
of maintenance temozolomide 150-200 mg/m(2) (day 1 to day 5) every 4 weeks. We
combined the survival data of 25 patients (already published) and five of our
patients and analyzed them in terms of progression free survival (PFS) and
overall survival (OS) using Kaplan-Meier method. RESULTS: Male to female ratio
was 1:4 and median age was 12 years (range, 7-19 years). All but one patient
underwent gross total resection and four patients completed adjuvant radiotherapy
as well as concurrent and adjuvant temozolomide. At a median follow up of 22.6
months (range, 0 to 45.3 months), two patients were dead and two were alive
without disease while one was lost to follow up. For the pooled data, estimated
median PFS and OS of all 30 patients reported in literature were 12 and 43
months, respectively. Two years PFS and OS rate for all patients was 44.2 and
62.9%, respectively. CONCLUSION: Adjuvant radiotherapy and temozolomide is well
tolerated and show an encouraging survival in pPGS.
PMID- 26438550
TI - First trimester diagnosis of cervico-thoracic diastematomyelia and diplomyelia
using three-dimensional ultrasound.
AB - BACKGROUND: Diastematomyelia and diplomyelia are rare form of spinal cord
malformations (SCM) characterized by sagittal cleft in the spinal cord, conus
medullaris, and/or filum terminale with splaying of the posterior vertebral
elements and duplication of the spinal cord into two twin cords. Prenatal
diagnosis of these diseases by two-dimensional ultrasound has been reported
usually late in pregnancy and only recently in the first trimester. OBJECTIVE: We
describe the first case of cervico-thoracic diastematomyelia and diplomyelia
diagnosed early in pregnancy using three-dimensional ultrasound.
PMID- 26438547
TI - The role of simulation in neurosurgery.
AB - PURPOSE: In an era of residency duty-hour restrictions, there has been a recent
effort to implement simulation-based training methods in neurosurgery teaching
institutions. Several surgical simulators have been developed, ranging from
physical models to sophisticated virtual reality systems. To date, there is a
paucity of information describing the clinical benefits of existing simulators
and the assessment strategies to help implement them into neurosurgical
curricula. Here, we present a systematic review of the current models of
simulation and discuss the state-of-the-art and future directions for simulation
in neurosurgery. METHODS: Retrospective literature review. RESULTS: Multiple
simulators have been developed for neurosurgical training, including those for
minimally invasive procedures, vascular, skull base, pediatric, tumor resection,
functional neurosurgery, and spine surgery. The pros and cons of existing systems
are reviewed. CONCLUSION: Advances in imaging and computer technology have led to
the development of different simulation models to complement traditional surgical
training. Sophisticated virtual reality (VR) simulators with haptic feedback and
impressive imaging technology have provided novel options for training in
neurosurgery. Breakthrough training simulation using 3D printing technology holds
promise for future simulation practice, proving high-fidelity patient-specific
models to complement residency surgical learning.
PMID- 26438549
TI - Tonsillar contusion associated with benign tonsillar ectopia following minor head
trauma.
AB - PURPOSE: The relationship between tonsil position and symptomatic cerebellar
contusion is unclear. To date, there are no reports of symptomatic traumatic
brain injury associated with benign tonsillar ectopia. Reported cases are limited
to prominent cerebellar tonsillar displacement by >=5 mm (i.e., Chiari
malformations). METHODS: The authors describe a case of symptomatic concussion in
a toddler with unusual computerized tomography (CT) presentation and incidental
finding of benign tonsillar ectopia, hemorrhagic contusion of the tonsils, blood
brain barrier (BBB) disruption and delayed atrophy shown using magnetic resonance
imaging (MRI) studies. The radiological presentation and the clinical challenges
are discussed through a review of the literature. CONCLUSION: This case suggests
that damage to cerebellar structures is not limited only to overt tonsillar
herniation. Benign tonsillar ectopia may predispose to cerebellar contusion even
after minor concussion and thus has a clinical significance. The current paradigm
viewing only noticeable tonsillar herniation as a risk factor for hindbrain
injury should be revisited.
PMID- 26438551
TI - Embolization of a giant hypervascularized choroid plexus papilloma with onyx by
direct puncture: a case report.
AB - BACKGROUND: Choroid plexus papilloma is a rare intracranial neoplasm derived from
choroid plexus epithelium accounting for less than 1 % of all brain tumors. These
tumors are highly vascularized, and tumor resection is difficult, especially in
small children, due to severe intraoperative bleeding. Preoperative embolization
is helpful to reduce intraoperative bleeding, but it may not be possible in small
children or if the tumor has no suitable feeding vessels for embolization.
METHODS: We present the case of a 2-year-old girl with a giant choroid plexus
papilloma. An attempt of tumor resection was previously performed in another
clinic, but the surgery was aborted due to massive intraoperative bleeding and
only a biopsy was done. Angiography showed no suitable vessels for embolization.
A new attempt of tumor removal was carried out, but again, severe intraoperative
bleeding occurred and only a partial resection was possible. Intratumoral
embolization with onyx through direct percutaneous puncture was performed.
RESULTS: Radical tumor removal was possible after two additional surgeries.
Intraoperative blood loss was 345 ml (first surgery = only partial removal), 250
ml (second procedure = 1/3 of tumor volume resected), and 250 ml (third surgery =
total removal). The patient presented no additional deficits. CONCLUSIONS:
Intratumoral percutaneous embolization with onyx was very helpful in reducing
intraoperative bleeding in this case. Safe radical tumor resection was possible.
This technique may be useful for those surgeons dealing with highly vascularized
tumors, especially in small children. No report of intratumoral embolization with
onyx in cases of intracerebral tumors could be found in the literature.
PMID- 26438552
TI - Rosette-forming glioneuronal tumor outside the fourth ventricle: a case-based
update.
AB - INTRODUCTION: Rosette-forming glioneuronal tumors (RGNTs) that do not involve the
fourth ventricle are rare. RGNTs were originally thought to be exclusively
localized into the fourth ventricle but were found in various anatomical
localizations. MATERIAL AND METHODS: We review the literature and found 32 cases
of this particular RGNT. The outcome was excellent with no mortality reported
after surgical treatment. Only two patients had received adjuvant therapy for
progression. We added one case of a RGNT located in the cerebellar hemisphere.
CASE AND CONCLUSION: She underwent a subtotal removal with no evidence of
progression after. This WHO grade I tumor with a specific biphasic histopathology
is of a good oncological outcome after surgical treatment. A long follow-up is
needed as recurrence or metastatic progressions exist.
PMID- 26438553
TI - No Evidence for Spontaneous Lipid Transfer at ER-PM Membrane Contact Sites.
AB - Non-vesicular lipid transport steps play a crucial role in lipid trafficking and
potentially include spontaneous exchange. Since membrane contact facilitates this
lipid transfer, it is most likely to occur at membrane contact sites (MCS).
However, to date it is unknown whether closely attached biological membranes
exchange lipids spontaneously. We have set up a system for studying the exchange
of lipids at MCS formed between the endoplasmic reticulum (ER) and the plasma
membrane. Contact sites were stably anchored and the lipids cholesterol and
phosphatidylcholine (PC) were not capable of transferring spontaneously into the
opposed bilayer. We conclude that physical contact between two associated
biological membranes is not sufficient for transfer of the lipids PC and
cholesterol.
PMID- 26438554
TI - Validation of the Modified Raymond-Roy classification for intracranial aneurysms
treated with coil embolization.
AB - BACKGROUND: The Raymond-Roy Occlusion Classification (RROC) qualitatively
assesses intracranial aneurysm occlusion following endovascular coil
embolization. The Modified Raymond-Roy Classification (MRRC) was developed as a
refinement of this classification scheme, and dichotomizes RROC III occlusions
into IIIa (opacification within the interstices of the coil mass) and IIIb
(opacification between the coil mass and aneurysm wall) closures. METHODS: To
demonstrate in an external cohort the predictive accuracy of the MRRC, the
records of 326 patients with 345 intracranial aneurysms treated with endovascular
coil embolization from January 2007 to December 2013 were retrospectively
analyzed. RESULTS: Within this cohort, 84 (24.3%) and 83 aneurysms (24.1%) had
MRRC IIIa and IIIb closures, respectively, during initial coil embolization.
Progression to complete occlusion was more likely with IIIa than IIIb closures
(53.6% vs 19.2%, p<=0.01), while recanalization was more likely with IIIb than
IIIa closures (65.1% vs 27.4%, p<0.01). Kaplan-Meier estimates demonstrated a
significant difference in the test of equality for progression to complete
occlusion (p=0.02) and recurrence (p<0.01) between class IIIa and IIIb
distributions. For the entire cohort, male gender (p<0.01), ruptured aneurysm
(p=0.04), intraluminal thrombus (p<0.01), and MRRC IIIb closure (p<0.01) were
identified as predictors of recanalization. For aneurysms with an initial RROC
III occlusion, MRRC IIIa closure was found to be an independent predictor of
progression to complete occlusion (p=0.02). CONCLUSIONS: This study confirms that
the MRRC enhances the predictive accuracy of the RROC.
PMID- 26438555
TI - Effect of electroacupuncture pretreatment at GB20 on behaviour and the descending
pain modulatory system in a rat model of migraine.
AB - BACKGROUND: While electroacupuncture (EA) pretreatment has been found to
ameliorate migraine-like symptoms, the underlying mechanisms remain poorly
understood. Emerging evidence suggests that the brainstem descending pain
modulatory system, comprising the periaqueductal grey (PAG), raphe magnus nucleus
(RMg), and trigeminal nucleus caudalis (TNC), may be involved in migraine
pathophysiology. We hypothesised that EA would ameliorate migraine-like symptoms
via modulation of this descending system. METHODS: We used a conscious rat model
of migraine induced by repeated electrical stimulation of the dura. Forty male
Sprague-Dawley rats were randomly assigned to one of four groups: an EA group,
which received EA at GB20 following dural stimulation; a sham acupuncture (SA)
group, which received manual acupuncture at a non-acupuncture point following
dural stimulation; a Model group, which received dural stimulation but no
acupuncture; and a Control group, which received neither dural stimulation nor
acupuncture (electrode implantation only). HomeCageScan was used to measure
effects on behaviour, and immunofluorescence staining was used to examine neural
activation (c-Fos immunoreactivity) in the PAG, RMg, and TNC. RESULTS: Compared
to the Model group, rats in the EA group showed a significant increase in
exploratory, locomotor and eating/drinking behaviour (p<0.01) and a significant
decrease in freezing-like resting and grooming behaviour (p<0.05). There was a
significant increase in the mean number of c-Fos neurons in the PAG, RMg, and TNC
in Model versus Control groups (p<0.001); however, this was significantly
attenuated by EA treatment (p<0.001). There were no significant differences
between the SA and Model groups in behaviour or c-Fos immunoreactivity.
CONCLUSIONS: EA pretreatment ameliorates behavioural changes in a rat model of
recurrent migraine, possibly via modulation of the brainstem descending pathways.
PMID- 26438556
TI - Laser acupuncture before heel lancing for pain management in healthy term
newborns: a randomised controlled trial.
AB - BACKGROUND: Healthy term newborns commonly undergo painful procedures during
routine follow-up visits. Non-pharmacological strategies have currently become
more important than pharmacological analgesic agents in neonatal pain management.
Acupuncture is a new non-pharmacological method for preventing pain in newborns.
OBJECTIVE: We aimed to investigate the effect of laser acupuncture (LA) at the
Yintang point before heel lancing as a non-pharmacological intervention for
procedural pain management in infants. METHODS: Forty-two term newborns, who were
undergoing heel lancing between postnatal days 3 to 8 as part of routine neonatal
screening, were randomly assigned to the LA group or the oral sucrose group. In
the LA group, 2 min before the heel lancing, 0.3 J of energy was applied to the
Yintang point using a Laser PREMIO-30 unit for 30 s. In the sucrose group, each
infant received 0.5 mL of 24% sucrose orally via syringe 2 min before the heel
lancing. Each baby's behaviour was scored using the Neonatal Infant Pain Scale
(NIPS), assessed blinded to group. RESULTS: There were no significant differences
between the LA and oral sucrose groups with respect to means for gestational week
of age at birth, birth weight, actual weight, or Apgar score. Mean procedure time
was significantly shorter in the LA group; however, mean crying time was longer
and NIPS score was lower compared to the oral sucrose group. CONCLUSIONS: Our
results indicate that 0.3 J of LA at the Yintang point before heel lancing is
less effective than oral sucrose for reducing the discomfort of this procedure.
TRIAL REGISTRATION NUMBER: KA14/09.
PMID- 26438557
TI - Auricular acupuncture for pre-exam anxiety in medical students: a prospective
observational pilot investigation.
AB - OBJECTIVE: Auricular acupuncture (AA) is effective for the treatment of
preoperative anxiety. We aimed to study the feasibility and effects of AA on exam
anxiety in a prospective observational pilot study. METHODS: Healthy medical
students received bilateral AA using indwelling fixed needles at points MA-IC1,
MA-TF1, MA-SC, MA-AH7, and MA-T on the day before an anatomy exam. The needles
were removed after the exam. Anxiety levels were measured using the State-Trait
Anxiety Inventory (STAI) and a 100 mm visual analogue scale (VAS-100) before and
after the AA intervention and once again immediately before the exam. The
duration of sleep on the night before the exam was recorded and compared to that
over the preceding 1 week and 6 months (all through students' recollection). In
addition, blood pressure, heart rate and the acceptability of AA to the students
were recorded. RESULTS: Ten students (all female) were included in the final
analysis. All tolerated the needles well and stated they would wish to receive AA
again for exam anxiety in the future. Exam anxiety measured using both STAI and
VAS-100 decreased by almost 20% after AA. CONCLUSIONS: AA was well accepted, the
outcome measurement was feasible, and the results have facilitated the
calculation of the sample size for a subsequent randomised controlled trial.
PMID- 26438558
TI - Backbone chemical shift assignments for Xanthomonas campestris peroxiredoxin Q in
the reduced and oxidized states: a dramatic change in backbone dynamics.
AB - Peroxiredoxins (Prx) are ubiquitous enzymes that reduce peroxides as part of
antioxidant defenses and redox signaling. While Prx catalytic activity and
sensitivity to hyperoxidative inactivation depend on their dynamic properties,
there are few examples where their dynamics has been characterized by NMR
spectroscopy. Here, we provide a foundation for studies of the solution
properties of peroxiredoxin Q from the plant pathogen Xanthomonas campestris
(XcPrxQ) by assigning the observable (1)H(N), (15)N, (13)C(alpha), (13)C(beta),
and (13)C' chemical shifts for both the reduced (dithiol) and oxidized
(disulfide) states. In the reduced state, most of the backbone amide resonances
(149/152, 98 %) can be assigned in the XcPrxQ (1)H-(15)N HSQC spectrum. In
contrast, a remarkable 51 % (77) of these amide resonances are not visible in the
(1)H-(15)N HSQC spectrum of the disulfide state of the enzyme, indicating a
substantial change in backbone dynamics associated with the formation of an
intramolecular C48-C84 disulfide bond.
PMID- 26438559
TI - Endothelin-1 induces LIMK2-mediated programmed necrotic neuronal death
independent of NOS activity.
AB - BACKGROUND: Recently, we have reported that LIM kinase 2 (LIMK2) involves
programmed necrotic neuronal deaths induced by aberrant cyclin D1 expression
following status epilepticus (SE). Up-regulation of LIMK2 expression induces
neuronal necrosis by impairment of dynamin-related protein 1 (DRP1)-mediated
mitochondrial fission. However, we could not elucidate the upstream effecter for
LIMK2-mediated neuronal death. Thus, we investigated the role of endothelin-1 (ET
1) in LIMK2-mediated neuronal necrosis, since ET-1 involves neuronal death via
various pathways. RESULTS: Following SE, ET-1 concentration and its mRNA were
significantly increased in the hippocampus with up-regulation of ETB receptor
expression. BQ788 (an ETB receptor antagonist) effectively attenuated SE-induced
neuronal damage as well as reduction in LIMK2 mRNA/protein expression. In
addition, BQ788 alleviated up-regulation of Rho kinase 1 (ROCK1) expression and
impairment of DRP1-mediated mitochondrial fission in CA1 neurons following SE.
BQ788 also attenuated neuronal death and up-regulation of LIMK2 expression
induced by exogenous ET-1 injection. CONCLUSION: These findings suggest that ET-1
may be one of the upstream effectors for programmed neuronal necrosis through
abnormal LIMK2 over-expression by ROCK1.
PMID- 26438560
TI - High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma:
tumor-associated neovascularization as a biomarker for patient survival. A
preliminary study.
AB - INTRODUCTION: The objective of the study was to determine whether tumor
associated neovascularization on high-resolution gadofosveset-enhanced magnetic
resonance angiography (MRA) is a useful biomarker for predicting survival in
patients with newly diagnosed glioblastomas. METHODS: Before treatment, 35
patients (25 men; mean age, 64 +/- 14 years) with glioblastoma underwent MRI
including first-pass dynamic susceptibility contrast (DSC) perfusion and post
contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high
resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast
enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter
were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic
factors were assessed by Kaplan-Meier survival and Cox proportional hazards
model. RESULTS: Eighteen (51.42 %) glioblastomas were hypervascular on high
resolution MRA. Hypervascular glioblastomas were associated with higher CEL
volume and lower Karnofsky score. Median survival rates for patients with
hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy,
and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor
associated neovascularization was the best predictor of survival at 5.25 months
(AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive
value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P
< 0.001). CONCLUSIONS: Tumor-associated neovascularization detected on high
resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems
to be a useful biomarker that correlates with worse survival.
PMID- 26438562
TI - Frequent Dilatation of the Descending Aorta in Children With Hypoplastic Left
Heart Syndrome Relates to Decreased Aortic Arch Elasticity.
AB - BACKGROUND: Patients with hypoplastic left heart syndrome after a Norwood
operation show dilatation and reduced distensibility of the reconstructed
proximal aorta. Cardiac magnetic resonance imaging (CMR) and angiographic
examinations indicate that the native descending aorta (DAo) is also dilated, but
this has not been studied in detail. METHODS AND RESULTS: Seventy-nine children
with hypoplastic left heart syndrome in Fontan circulation (aged 6.3+/-3.2 years)
and 18 control participants (aged 6.8+/-2.4 years) underwent 3.0-tesla CMR.
Gradient-echo cine and phase-contrast imaging was applied to measure cross
sectional areas (CSAs), distensibility, pulse wave velocity, and the incremental
elastic modulus of the thoracic aorta. CSA of the DAo in patients was also
compared with published percentiles for aortic CSA. Patients had significantly
larger CSA of the DAo at the level of pulmonary artery bifurcation (229.1+/-97.2
versus 175.7+/-24.3 mm/m(2), P=0.04) and the diaphragm (196.2+/-66.0 versus
142.6+/-16.7 mm/m(2), P<0.01). In 41 patients (52%), CSA of the DAo was >95th
percentile level for control participants, and the incremental elastic modulus of
the aortic arch and the DAo was higher than in patients with normal CSAs (arch:
90.1+/-64.3 versus 45.6+/-38.9 m/s; DAo: 86.3+/-53.7 versus 47.1+/-47.6 m/s;
P<0.01). Incremental elastic modulus of the aortic arch and the DAo correlated
with the CSA of the DAo (arch: r=0.5; DAo: r=0.49; P<0.01). CONCLUSIONS: Children
with hypoplastic left heart syndrome frequently show dilatation of their DAo
associated with increased stiffness of the aortic arch. Higher aortic impedance
increases the afterload of the systemic circulation and likely contributes to the
burden of the systemic right ventricle.
PMID- 26438561
TI - PGC-1alpha-mediated changes in phospholipid profiles of exercise-trained skeletal
muscle.
AB - Exercise training influences phospholipid fatty acid composition in skeletal
muscle and these changes are associated with physiological phenotypes; however,
the molecular mechanism of this influence on compositional changes is poorly
understood. Peroxisome proliferator-activated receptor gamma coactivator 1alpha
(PGC-1alpha), a nuclear receptor coactivator, promotes mitochondrial biogenesis,
the fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle.
Because exercise training induces these adaptations, together with increased PGC
1alpha, PGC-1alpha may contribute to the exercise-mediated change in phospholipid
fatty acid composition. To determine the role of PGC-1alpha, we performed
lipidomic analyses of skeletal muscle from genetically modified mice that
overexpress PGC-1alpha in skeletal muscle or that carry KO alleles of PGC-1alpha.
We found that PGC-1alpha affected lipid profiles in skeletal muscle and increased
several phospholipid species in glycolytic muscle, namely phosphatidylcholine
(PC) (18:0/22:6) and phosphatidylethanolamine (PE) (18:0/22:6). We also found
that exercise training increased PC (18:0/22:6) and PE (18:0/22:6) in glycolytic
muscle and that PGC-1alpha was required for these alterations. Because
phospholipid fatty acid composition influences cell permeability and receptor
stability at the cell membrane, these phospholipids may contribute to exercise
training-mediated functional changes in the skeletal muscle.
PMID- 26438563
TI - Comparison between whole-body inhalation and nose-only inhalation on the
deposition and health effects of nanoparticles.
AB - OBJECTIVES: We performed the two inhalation exposures, whole-body inhalation and
nose-only inhalation, to investigate the pulmonary deposition and health effects
of the two inhalation methods. METHODS: In both methods, we exposed rats to the
same TiO2 nanoparticles at almost the same exposure concentration for 6 h and
compared the deposited amounts of nanoparticles and histopathological changes in
the lungs. Rats were exposed to rutile-type TiO2 nanoparticles generated by the
spray-dry method for 6 h. The exposure concentration in the whole-body chamber
was 4.10 +/- 1.07 mg/m(3), and that in nose-only chamber was 4.01 +/- 1.11
mg/m(3). The particle sizes were 230 and 180 nm, respectively. A control group
was exposed to fresh air. RESULTS: The amounts of TiO2 deposited in the lungs as
measured by ICP-AES after acid digestion just after the exposure were: 42.6 +/-
3.5 MUg in the whole-body exposure and 46.0 +/- 7.7 MUg in the nose-only exposure
groups. The histopathological evaluation was the same in both exposure groups: no
infiltration of inflammatory cells in the alveolar space and interstitium, and no
fibrosis. CONCLUSION: The two inhalation methods using the same material under
the same exposure conditions resulted in the same particle deposition and
histopathology in the lung.
PMID- 26438566
TI - Evaluation of a ring enhancing lesion.
PMID- 26438565
TI - Signet-ring cell carcinoma of the rectum and synchronous renal cell carcinoma in
a young man.
PMID- 26438564
TI - Indomethacin induced gene regulation in the rat hippocampus.
AB - BACKGROUND: Non-steroidal anti-inflammatory drugs such as indomethacin are widely
used to treat inflammatory diseases and manage pain, fever and inflammation in
several conditions, including neuropsychiatric disorders. Although they
predominantly function by inhibiting cyclooxygenase (COX) activity, important COX
independent actions also occur. These actions could be responsible for the
adverse side effects associated with chronic and/or high dose usage of this
popular drug class. RESULTS: We examined gene regulation in the hippocampus after
peripheral administration of indomethacin by employing a microarray approach.
Secondary confirmation and the brain expression pattern of regulated genes was
examined by in situ hybridization and immunohistochemistry. Transglutaminase 2,
serum glucocorticoid inducible kinase, Inhibitor of NF-kappa B and vascular
endothelial growth factor were among genes that were prominently upregulated,
while G-protein coupled receptor 56 and neuropeptide Y were among genes that were
downregulated by indomethacin. Co-localization studies using blood vessel markers
revealed that transglutaminase 2 was induced specifically in brain vasculature.
CONCLUSIONS: The data demonstrate that COX-inhibitors can differentially regulate
gene transcription in multiple, functionally distinctly cell types in the brain.
The results provide additional insight into the molecular actions of COX
inhibitors and indicate that their effects on vasculature could influence
cerebral blood flow mechanisms.
PMID- 26438567
TI - Celebrating 75 years of oestradiol.
AB - Oestrogens exert important effects on the reproductive as well as many other
organ systems in both men and women. The history of the discovery of oestrogens,
the mechanisms of their synthesis, and their therapeutic applications are very
important components of the fabric of endocrinology. These aspects provide the
rationale for highlighting several key components of this story. Two
investigators, Edward Doisy and Alfred Butenandt, purified and crystalized
oestrone nearly simultaneously in 1929, and Doisy later discovered oestriol and
oestradiol. Butenandt won the Nobel Prize for this work and Doisy's had to await
his purification of vitamin K. Early investigators quickly recognized that
oestrogens must be synthesized from androgens and later investigators called this
process aromatization. The aromatase enzyme was then characterized, its mechanism
determined, and its structure identified after successful crystallization. With
the development of knock-out methodology, the precise effects of oestrogen in
males and females were defined and clinical syndromes of deficiency and excess
described. Their discovery ultimately led to the development of oral
contraceptives, treatment of menopausal symptoms, therapies for breast cancer,
and induction of fertility, among others. The history of the use of oestrogens
for postmenopausal women to relieve symptoms has been characterized by cyclic
periods of enthusiasm and concern. The individuals involved in these studies, the
innovative thinking required, and the detailed understanding made possible by
evolving biologic and molecular techniques provide many lessons for current
endocrinologists.
PMID- 26438568
TI - Non-coding genome functions in diabetes.
AB - Most of the genetic variation associated with diabetes, through genome-wide
association studies, does not reside in protein-coding regions, making the
identification of functional variants and their eventual translation to the
clinic challenging. In recent years, high-throughput sequencing-based methods
have enabled genome-scale high-resolution epigenomic profiling in a variety of
human tissues, allowing the exploration of the human genome outside of the well
studied coding regions. These experiments unmasked tens of thousands of
regulatory elements across several cell types, including diabetes-relevant
tissues, providing new insights into their mechanisms of gene regulation.
Regulatory landscapes are highly dynamic and cell-type specific and, being
sensitive to DNA sequence variation, can vary with individual genomes. The
scientific community is now in place to exploit the regulatory maps of tissues
central to diabetes etiology, such as pancreatic progenitors and adult islets.
This giant leap forward in the understanding of pancreatic gene regulation is
revolutionizing our capacity to discriminate between functional and non
functional non-coding variants, opening opportunities to uncover regulatory links
between sequence variation and diabetes susceptibility. In this review, we focus
on the non-coding regulatory landscape of the pancreatic endocrine cells and
provide an overview of the recent developments in this field.
PMID- 26438569
TI - Rhetorical functions of a 'language of uncertainty' in the mass media.
AB - As linguists, we are interested in the way uncertainty, understood as a range of
epistemic qualities related to not knowing, is dealt with linguistically in
communicative contexts involving scientists, the mass media and the public. One
of our central theses is that uncertainty in journalistic texts is not only
reflected at different linguistic levels but that it also has various rhetorical
functions. Through close analysis of a German newspaper article about geo
engineering, we show which specific linguistic forms, categories and structures
are used when dealing with uncertainty, and which rhetorical functions of
uncertainty are identifiable in the text. We conclude from our analysis that a
'language of (un-)certainty' is always highly context sensitive, meaning that the
linguistic resources used to express uncertainty are both multifaceted and
multifunctional.
PMID- 26438570
TI - Discourse over a contested technology on Twitter: A case study of hydraulic
fracturing.
AB - High-volume hydraulic fracturing, a drilling simulation technique commonly
referred to as "fracking," is a contested technology. In this article, we explore
discourse over hydraulic fracturing and the shale industry on the social media
platform Twitter during a period of heightened public contention regarding the
application of the technology. We study the relative prominence of negative
messaging about shale development in relation to pro-shale messaging on Twitter
across five hashtags (#fracking, #globalfrackdown, #natgas, #shale, and
#shalegas). We analyze the top actors tweeting using the #fracking hashtag and
receiving @mentions with the hashtag. Results show statistically significant
differences in the sentiment about hydraulic fracturing and shale development
across the five hashtags. In addition, results show that the discourse on the
main contested hashtag #fracking is dominated by activists, both individual
activists and organizations. The highest proportion of tweeters, those posting
messages using the hashtag #fracking, were individual activists, while the
highest proportion of @mention references went to activist organizations.
PMID- 26438571
TI - Former Tory health minister attacks new junior doctor contract.
PMID- 26438572
TI - A Checklist of Chigger Mites (Acari: Trombiculidae and Leeuwenhokiidae) From
Taiwan, With Descriptions of Three New Species.
AB - Scrub typhus is a lethal human disease transmitted by larval trombiculid mites
(i.e., chiggers) that have been infected with the rickettsia Orientia
tsutsugamushi. In total, 21 chigger species are known from Taiwan. We update the
checklist of chiggers of Taiwan based on an intensive survey of shrew and rodent
hosts in grasslands and agricultural fields in lowland Taiwan, coupled with
surveys of forests in one mountainous site and an opportunistic examination of
submitted host specimens. Three new species of chiggers, Gahrliepia (Gateria)
lieni sp. n., Gahrliepia (Gateria) minuta sp. n., and Gahrliepia (Gateria)
yilanensis sp. n., as well as 23 newly recorded chigger species, were discovered.
Accordingly, recorded chigger species of Taiwan more than doubled from 21 to 47
species. Two new species and nine newly recorded chigger species were discovered
in forests in one mountainous site in northeastern Taiwan, suggesting that many
more chigger species may be uncovered, particularly in mountainous Taiwan.
Further studies should also investigate O. tsutsugamushi infection in different
chigger species to assess its risks to human health.
PMID- 26438573
TI - NHS must reform to avoid "busting" public finances, says health secretary.
PMID- 26438574
TI - Health and Economic Impact of Switching from a 4-Valent to a 9-Valent HPV
Vaccination Program in the United States.
AB - BACKGROUND: Randomized clinical trials have shown the 9-valent human
papillomavirus (HPV) vaccine to be highly effective against types 31/33/45/52/58
compared with the 4-valent. Evidence on the added health and economic benefit of
the 9-valent is required for policy decisions. We compare population-level
effectiveness and cost-effectiveness of 9- and 4-valent HPV vaccination in the
United States. METHODS: We used a multitype individual-based transmission-dynamic
model of HPV infection and disease (anogenital warts and cervical, anogenital,
and oropharyngeal cancers), 3% discount rate, and societal perspective. The model
was calibrated to sexual behavior and epidemiologic data from the United States.
In our base-case, we assumed 95% vaccine-type efficacy, lifelong protection, and
a cost/dose of $145 and $158 for the 4- and 9-valent vaccine, respectively.
Predictions are presented using the mean (80% uncertainty interval [UI] = 10(th)
90(th) percentiles) of simulations. RESULTS: Under base-case assumptions, the 4
valent gender-neutral vaccination program is estimated to cost $5500 (80% UI =
2400-9400) and $7300 (80% UI = 4300-11 000)/quality-adjusted life-year (QALY)
gained with and without cross-protection, respectively. Switching to a 9-valent
gender-neutral program is estimated to be cost-saving irrespective of cross
protection assumptions. Finally, the incremental cost/QALY gained of switching to
a 9-valent gender-neutral program (vs 9-valent girls/4-valent boys) is estimated
to be $140 200 (80% UI = 4200->1 million) and $31 100 (80% UI = 2100->1 million)
with and without cross-protection, respectively. Results are robust to
assumptions about HPV natural history, screening methods, duration of protection,
and healthcare costs. CONCLUSIONS: Switching to a 9-valent gender-neutral HPV
vaccination program is likely to be cost-saving if the additional cost/dose of
the 9-valent is less than $13. Giving females the 9-valent vaccine provides the
majority of benefits of a gender-neutral strategy.
PMID- 26438575
TI - Hospice Use Among Patients With Lymphoma: Impact of Disease Aggressiveness and
Curability.
AB - BACKGROUND: Little is known about factors that influence hospice use for patients
with blood cancers. We aimed to characterize hospice enrollment in a large
population of patients with B-cell non-Hodgkin lymphoma (NHL) and assess the
impact of disease characteristics such as aggressiveness and curability. METHODS:
Using the Surveillance, Epidemiology, and End Results-Medicare database, we
identified patients age 65 years and older who were diagnosed with indolent NHL,
aggressive NHL, or mantle cell lymphoma (MCL, which is aggressive and incurable)
and died between 1999 and 2009. We determined the prevalence of hospice use and
predictors thereof, using multivariable logistic regression. All statistical
tests were two-sided. RESULTS: Of 18 777 patients, 9645 had indolent NHL, 8226
had aggressive NHL, and 906 had MCL. Of the total cohort, 41.6% enrolled in
hospice, and 34.3% enrolled three or more days before death. Compared with
patients with indolent NHL, those with MCL were more likely to enroll (adjusted
odds ratio [AOR] = 1.72, 95% confidence interval [CI] = 1.49 to 1.98), followed
by patients with aggressive NHL (AOR = 1.41, 95% CI = 1.32 to 1.50). Other
factors statistically significantly associated with hospice use included older
age, female sex, white race, high socioeconomic status, and later year of death.
CONCLUSIONS: In this large cohort of patients with lymphoma, hospice use was
substantially lower than the national average for all cancers, suggesting either
the need for improvement in enrollment or that the current hospice model is not
meeting this population's end-of-life needs. Moreover, the fact that patients
with MCL were most likely to enroll suggests that the end-of-life phase may be
more easily determined in the context of cancers that are both aggressive and
incurable.
PMID- 26438576
TI - Margaret McCartney: Honesty, placebos, and pain care.
PMID- 26438577
TI - Are neurofilaments heading for the ALS clinic?
PMID- 26438578
TI - Does a popular documentary about a "life saving" heart scan promote
overtreatment?
PMID- 26438579
TI - Care Coordination and Transition of Men's Health Management.
PMID- 26438580
TI - Training for contingency operations; a potential role for regional training days?
PMID- 26438581
TI - Medical and DNBI admissions to the Role 3 field hospital at Camp Bastion during
Operation Herrick.
PMID- 26438582
TI - Angiotensin receptor blockers use and the risk of lung cancer: A meta-analysis.
AB - BACKGROUND: Several reports suggest that the use of angiotensin receptor blockers
(ARBs) is associated with lung cancer (LC) reduction. However, the results were
contradictory. METHODS: Four online databases were searched. The strength of the
association between ARB and the risk of LC was measured by odds ratio (OR) and
95% confidence interval (CI). OR was analyzed by random-effects model. RESULTS:
Eight studies with 298000 subjects were included in this meta-analysis. Using of
ARB was significantly associated with decreased LC risk (OR = 0.81; 95% CI 0.69
0.94; p = 0.005). In the subgroup analysis by race, Asians treated with ARB
showed decreased LC risk (OR = 0.60; 95% CI 0.54-0.67; p < 0.00001). However,
Caucasians treated with ARB did not show significantly decreased LC risk (OR =
0.90; 95% CI 0.79-1.02; p = 0.11). Subgroup analysis by duration of follow-up was
conducted. The studies with less than 5 years showed significant result (OR =
0.79; 95% CI 0.64-0.97;p = 0.02). However, the studies with more than 5 years did
not show significantly decreased LC risk (OR = 0.84; 95% CI 0.61-1.16; p = 0.29).
CONCLUSIONS: This meta-analysis indicated that ARBs may be associated with
decreased risk of LC.
PMID- 26438583
TI - Experts call for snakebite to be re-established as a neglected tropical disease.
PMID- 26438585
TI - PUS has gone global in documenting the local culture of science.
PMID- 26438587
TI - Aspergillosis spores and medical marijuana.
PMID- 26438584
TI - Celiac disease and non-celiac gluten sensitivity.
AB - Celiac disease is a multisystem immune based disorder that is triggered by the
ingestion of gluten in genetically susceptible individuals. The prevalence of
celiac disease has risen in recent decades and is currently about 1% in most
Western populations. The reason for this rise is unknown, although environmental
factors related to the hygiene hypothesis are suspected. The pathophysiology of
celiac disease involves both the innate and adaptive immune response to dietary
gluten. Clinical features are diverse and include gastrointestinal symptoms,
metabolic bone disease, infertility, and many other manifestations. Although a
gluten-free diet is effective in most patients, this diet can be burdensome and
can limit quality of life; consequently, non-dietary therapies are at various
stages of development. This review also covers non-celiac gluten sensitivity. The
pathophysiology of this clinical phenotype is poorly understood, but it is a
cause of increasing interest in gluten-free diets in the general population.
PMID- 26438588
TI - Clinical trial transparency.
PMID- 26438589
TI - An epidemiological paradox.
PMID- 26438590
TI - The art of medicine.
PMID- 26438591
TI - Long-term use of diphenhydramine.
PMID- 26438593
TI - What next for environmental health?
AB - AIMS: The aim of the wider research was to explore Health and Wellbeing Boards
(HWBs) during their early development stages, with a focus on health inequalities
and the role of environmental health (EH). This article presents empirical
findings relating to challenges facing the EH profession in the new English
public health (PH) system and offers new practical suggestions as to how they
might be overcome in relation to educating and training the new generation of EH
practitioners (EHPs). METHODS: Four case study HWBs in the Midlands and North of
England were followed for 18 months from early 2012. In addition, EHPs and
managers from each English region were interviewed. In total, 50 semi-structured
interviews were carried out, around 55 h of HWB meetings were observed, and
documents associated with HWBs such as strategies and minutes of meetings were
collected. Data were analysed thematically, both inductively and deductively,
using Atlas.ti. RESULTS: EH is largely invisible in the new PH system due to a
variety of internal and external factors, including existing skill sets and
practices. There is a new imperative to move away from reliance on statutory
functions for funding and to engage with wider PH issues and colleagues,
requiring new skills of evaluation and a change in perception from being 'doers'
to include a greater role as 'thinkers'. This is being recognised by EHPs and
managers, who are seeking ways to adapt to these new expectations. CONCLUSION:
Recent changes to the English PH system have led to a period of reflection and
the beginnings of adaptation in EH to overcome new challenges. Linked to this is
a need for graduate training to prepare new practitioners to think critically, to
thrive and become high-level managers of the future, while being technically
competent. We suggest a new, enhanced role for Chartered Institute of
Environmental Health (CIEH)-accredited universities in securing the future of the
profession by supporting new graduates. Specifically, a mentoring scheme could be
introduced for the practical training element for new practitioners. This would
help to embed criticality and evaluation in practice, provide consistency in
training, and overcome the disconnect between academia and practice.
PMID- 26438592
TI - Modulation of Breast Cancer Risk Biomarkers by High-Dose Omega-3 Fatty Acids:
Phase II Pilot Study in Premenopausal Women.
AB - Higher intakes of the omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA) relative to the omega-6 arachidonic acid (AA) have been variably
associated with reduced risk of premenopausal breast cancer. The purpose of this
pilot trial was to assess feasibility and explore the effects of high-dose EPA
and DHA on blood and benign breast tissue risk biomarkers before design of a
placebo-controlled phase IIB trial. Premenopausal women with evidence of
hyperplasia +/- atypia by baseline random periareolar fine needle aspiration were
given 1860 mg of EPA + 1500 mg of DHA ethyl esters daily for 6 months. Blood and
benign breast tissue were sampled during the same menstrual cycle phase prestudy
and a median of 3 weeks after last dose. Additional blood was obtained within 24
hours of last dose. Feasibility, which was predefined as 50% uptake, 85%
retention, and 70% compliance, was demonstrated with 46% uptake, 94% completion,
and 85% compliance. Cytologic atypia decreased from 77% to 38% (P = 0.002), and
Ki-67 from a median of 2.1% to 1.0% (P = 0.021) with an increase in the ratio of
EPA + DHA to AA in erythrocyte phospholipids but no change in blood hormones,
adipokines, or cytokines. Exploratory breast proteomics assessment showed
decreases in several proteins involved in hormone and cytokine signaling with
mixed effects on those in the AKT/mTOR pathways. Further investigation of EPA
plus DHA for breast cancer prevention in a placebo-controlled trial in
premenopausal women is warranted.
PMID- 26438594
TI - Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer
Cells by Altering the Chemokine Microenvironment.
AB - Natural killer (NK) cells are key innate immune effectors against multiple
myeloma, their activity declining in multiple myeloma patients with disease
progression. To identify the mechanisms underlying NK cell functional impairment,
we characterized the distribution of functionally distinct NK cell subsets in the
bone marrow of multiple myeloma-bearing mice. Herein we report that the number of
KLRG1(-) NK cells endowed with potent effector function rapidly and selectively
decreases in bone marrow during multiple myeloma growth, this correlating with
decreased bone marrow NK cell degranulation in vivo. Altered NK cell subset
distribution was dependent on skewed chemokine/chemokine receptor axes in the
multiple myeloma microenvironment, with rapid downmodulation of the chemokine
receptor CXCR3 on NK cells, increased CXCL9 and CXCL10, and decreased CXCL12
expression in bone marrow. Similar alterations in chemokine receptor/chemokine
axes were observed in patients with multiple myeloma. Adoptive transfer
experiments demonstrated that KLRG1(-) NK cell migration to the bone marrow was
more efficient in healthy than multiple myeloma-bearing mice. Furthermore, bone
marrow localization of transferred CXCR3-deficient NK cells with respect to wild
type was enhanced in healthy and multiple myeloma-bearing mice, suggesting that
CXCR3 restrains bone marrow NK cell trafficking. Our results indicate that
multiple myeloma-promoted CXCR3 ligand upregulation together with CXCL12
downmodulation act as exit signals driving effector NK cells outside the bone
marrow, thus weakening the antitumor immune response at the primary site of tumor
growth.
PMID- 26438595
TI - In Vitro Models for Neurogenesis.
AB - The process of generating new neurons of different phenotype and function from
undifferentiated stem and progenitor cells starts at very early stages of
development and continues in discrete regions of the mammalian nervous system
throughout life. Understanding mechanisms underlying neuronal cell development,
biology, function, and interaction with other cells, especially in the neurogenic
niche of fully developed adults, is important in defining and developing new
therapeutic regimes in regenerative neuroscience. Studying these complex and
dynamic processes in vivo is challenging because of the complexity of the nervous
system and the presence of many known and unknown confounding variables. However,
the challenges could be overcome with simple and robust in vitro models that more
or less recapitulate the in vivo events. In this work, we will present an
overview of present available in vitro cell-based models of neurogenesis.
PMID- 26438597
TI - Matrix Metalloproteinase 1 Causes Vasoconstriction and Enhances Vessel Reactivity
to Angiotensin II via Protease-Activated Receptor 1.
AB - Matrix metalloproteinase 1 (MMP-1) is an activator of protease-activated receptor
1 (PAR-1), which is known to mediate the release of endothelin 1 (ET-1) in
endothelial cells and activate the RhoA kinase (ROCK) pathway. Recently, we
reported increased serum and vascular MMP-1 in women with preeclampsia and
hypothesized that the action of MMP-1 on PAR-1 might have vasoconstrictive
effects. Resistance-sized omental arteries obtained from normal pregnant women
were mounted on a myograph system and perfused with MMP-1 in a dose range of
0.025 to 25 ng/mL or with angiotensin II (Ang II) in a dose range of 0.001 to 10
umol/L in the presence of intraluminal MMP-1 (2.5 ng/mL) perfusion. Angiotensin
II dose response was also performed with omental arteries from women with
preeclampsia. Matrix metalloproteinase 1 caused dose-dependent vasoconstriction
in endothelium-intact, but not in endothelium-denuded, vessels from normal
pregnant women, which was blocked by inhibitors of PAR-1 and ET-1 type A receptor
blocker. Intraluminal perfusion with a constant amount of MMP-1 enhanced vessel
reactivity to Ang II, which was blocked by inhibitors of PAR-1, ROCK, and ET-1.
Enhanced vascular reactivity to Ang II was observed in endothelium-intact, but
not in endothelium-denuded, arteries of women with preeclampsia. Inhibitors of
PAR-1, ROCK, and ET-1 blocked enhanced vascular reactivity to Ang II in
endothelium-intact preeclamptic arteries. These data demonstrate that MMP-1 has
potent vasoconstrictor effects and the ability to enhance vascular reactivity to
vasoconstrictor hormones, which are mediated by an endothelial PAR-1, ROCK, and
ET-1 pathway. Increased circulating levels of MMP-1 and its increased expression
in systemic vessels of women with preeclampsia may contribute to the development
of maternal hypertension.
PMID- 26438598
TI - Posttranscriptional Regulation of the Inflammatory Marker C-Reactive Protein by
the RNA-Binding Protein HuR and MicroRNA 637.
AB - C-reactive protein (CRP), an acute-phase plasma protein, is a major component of
inflammatory reactions functioning as a mediator of innate immunity. It has been
widely used as a validated clinical biomarker of the inflammatory state in
trauma, infection, and age-associated chronic diseases, including cancer and
cardiovascular disease (CVD). Despite this, the molecular mechanisms that
regulate CRP expression are not well understood. Given that the CRP 3'
untranslated region (UTR) is long and AU rich, we hypothesized that CRP may be
regulated posttranscriptionally by RNA-binding proteins (RBPs) and by microRNAs.
Here, we found that the RBP HuR bound directly to the CRP 3' UTR and affected CRP
mRNA levels. Through this interaction, HuR selectively increased CRP mRNA
stability and promoted CRP translation. Interestingly, treatment with the age
associated inflammatory cytokine interleukin-6 (IL-6) increased binding of HuR to
CRP mRNA, and conversely, HuR was required for IL-6-mediated upregulation of CRP
expression. In addition, we identified microRNA 637 (miR-637) as a microRNA that
potently inhibited CRP expression in competition with HuR. Taken together, we
have uncovered an important posttranscriptional mechanism that modulates the
expression of the inflammatory marker CRP, which may be utilized in the
development of treatments for inflammatory processes that cause CVD and age
related diseases.
PMID- 26438596
TI - Memory Retrieval in Mice and Men.
AB - Retrieval, the use of learned information, was until recently mostly terra
incognita in the neurobiology of memory, owing to shortage of research methods
with the spatiotemporal resolution required to identify and dissect fast
reactivation or reconstruction of complex memories in the mammalian brain. The
development of novel paradigms, model systems, and new tools in molecular
genetics, electrophysiology, optogenetics, in situ microscopy, and functional
imaging, have contributed markedly in recent years to our ability to investigate
brain mechanisms of retrieval. We review selected developments in the study of
explicit retrieval in the rodent and human brain. The picture that emerges is
that retrieval involves coordinated fast interplay of sparse and distributed
corticohippocampal and neocortical networks that may permit permutational binding
of representational elements to yield specific representations. These
representations are driven largely by the activity patterns shaped during
encoding, but are malleable, subject to the influence of time and interaction of
the existing memory with novel information.
PMID- 26438599
TI - Cotargeting Polo-Like Kinase 1 and the Wnt/beta-Catenin Signaling Pathway in
Castration-Resistant Prostate Cancer.
AB - The Wnt/beta-catenin signaling pathway has been identified as one of the
predominantly upregulated pathways in castration-resistant prostate cancer
(CRPC). However, whether targeting the beta-catenin pathway will prove effective
as a CRPC treatment remains unknown. Polo-like kinase 1 (Plk1) is a critical
regulator in many cell cycle events, and its level is significantly elevated upon
castration of mice carrying xenograft prostate tumors. Indeed, inhibition of Plk1
has been shown to inhibit tumor growth in several in vivo studies. Here, we show
that Plk1 is a negative regulator of Wnt/beta-catenin signaling. Plk1 inhibition
or depletion enhances the level of cytosolic and nuclear beta-catenin in human
prostate cancer cells. Furthermore, inhibition of Wnt/beta-catenin signaling
significantly potentiates the antineoplastic activity of the Plk1 inhibitor
BI2536 in both cultured prostate cancer cells and CRPC xenograft tumors.
Mechanistically, axin2, a negative regulator of the beta-catenin pathway, serves
as a substrate of Plk1, and Plk1 phosphorylation of axin2 facilitates the
degradation of beta-catenin by enhancing binding between glycogen synthase kinase
3beta (GSK3beta) and beta-catenin. Plk1-phosphorylated axin2 also exhibits
resistance to Cdc20-mediated degradation. Overall, this study identifies a novel
Plk1-Wnt signaling axis in prostate cancer, offering a promising new therapeutic
option to treat CRPC.
PMID- 26438600
TI - Lysine Acetylation of CREBH Regulates Fasting-Induced Hepatic Lipid Metabolism.
AB - Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific
(CREBH), is a hepatic transcription factor that functions as a key regulator of
energy homeostasis. Here, we defined a regulatory CREBH posttranslational
modification process, namely, lysine-specific acetylation, and its functional
involvement in fasting-induced hepatic lipid metabolism. Fasting induces CREBH
acetylation in mouse livers in a time-dependent manner, and this event is
critical for CREBH transcriptional activity in regulating hepatic lipid
homeostasis. The histone acetyltransferase PCAF-mediated acetylation and the
deacetylase sirtuin-1-mediated deacetylation coexist to maintain CREBH
acetylation states under fasting conditions. Site-directed mutagenesis and
functional analyses revealed that the lysine (K) residue at position 294 (K294)
within the bZIP domain of the CREBH protein is the site where fasting-induced
acetylation/deacetylation occurs. Introduction of the acetylation-deficient
(K294R) or acetylation-mimicking (K294Q) mutation inhibited or enhanced CREBH
transcriptional activity, respectively. Importantly, CREBH acetylation at lysine
294 was required for the interaction and synergy between CREBH and peroxisome
proliferator-activated receptor alpha (PPARalpha) in activating their target
genes upon fasting or glucagon stimulation. Introduction of the CREBH lysine 294
mutation in the liver leads to hepatic steatosis and hyperlipidemia in animals
under prolonged fasting. In summary, our study reveals a molecular mechanism by
which fasting or glucagon stimulation modulates lipid homeostasis through
acetylation of CREBH.
PMID- 26438601
TI - The LSD1 Family of Histone Demethylases and the Pumilio Posttranscriptional
Repressor Function in a Complex Regulatory Feedback Loop.
AB - The lysine (K)-specific demethylase (LSD1) family of histone demethylases
regulates chromatin structure and the transcriptional potential of genes. LSD1 is
frequently deregulated in tumors, and depletion of LSD1 family members causes
developmental defects. Here, we report that reductions in the expression of the
Pumilio (PUM) translational repressor complex enhanced phenotypes due to dLsd1
depletion in Drosophila. We show that the PUM complex is a target of LSD1
regulation in fly and mammalian cells and that its expression is inversely
correlated with LSD1 levels in human bladder carcinoma. Unexpectedly, we find
that PUM posttranscriptionally regulates LSD1 family protein levels in flies and
human cells, indicating the existence of feedback loops between the LSD1 family
and the PUM complex. Our results highlight a new posttranscriptional mechanism
regulating LSD1 activity and suggest that the feedback loop between the LSD1
family and the PUM complex may be functionally important during development and
in human malignancies.
PMID- 26438603
TI - Ablation of osteopontin suppresses N-methyl-N-nitrosourea and Helicobacter pylori
induced gastric cancer development in mice.
AB - Several clinical studies have reported increased expression of osteopontin (OPN)
in various types of human cancer, including gastric cancer. However, the precise
mechanisms underlying tumor development remain unclear. In the present study, we
investigated the pathogenic roles of OPN in Helicobacter pylori-induced gastric
cancer development. Wild-type (WT) and OPN knockout (KO) mice were treated with N
methyl-N-nitrosourea (MNU) and infected with H.pylori. Mice were killed 50 weeks
after treatment, and stomach tissues were assessed by histopathological
examination, immunohistochemistry, quantitative real-time RT-PCR and western
blotting. To clarify the carcinogenic effects of OPN, we also conducted an in
vitro study using AGS human gastric cancer cell line and THP-1 human monocytic
cell line. The overall incidence of gastric tumors was significantly decreased in
OPN KO mice compared with WT mice. Apoptotic cell death was significantly
enhanced in OPN KO mice and was accompanied by upregulation of signal transducer
and activator of transcription 1 (STAT1) and inducible nitric oxide synthase
(iNOS). In vitro study, OPN suppression also caused STAT1 upregulation and iNOS
overexpression in AGS and THP-1 cells, which resulted in apoptosis of AGS cells.
In addition, a negative correlation was clearly identified between expression of
OPN and iNOS in human gastric cancer tissues. Our data demonstrate that loss of
OPN decreases H.pylori-induced gastric carcinogenesis by suppressing
proinflammatory immune response and augmenting STAT1 and iNOS-mediated apoptosis
of gastric epithelial cells. An important implication of these findings is that
OPN actually contributes to the development of gastric cancer.
PMID- 26438604
TI - Trichomonas vaginalis infection in Nigerian pregnant women and risk factors
associated with sexually transmitted infections.
AB - Trichomoniasis poses a public health threat to pregnant women and neonatal
health. This study evaluated Trichomonas vaginalis and other common sexually
transmitted infections (STIs) status in pregnant women, and risk factors
associated with them. The study was cross-sectional and descriptive and a total
of 198 pregnant women were recruited for T. vaginalis screening by microscopic
examination. Questionnaires were also administered to 108 pregnant women to
access information related to socio-demography and other factors associated with
STI transmission. The overall prevalence of T. vaginalis was 18.7%. While
prevalence of T. vaginalis was neither age nor parity dependent (p > 0.05), women
in their first trimester showed significantly higher prevalence of trichomoniasis
compared to women in their second and third trimesters (p < 0.05). The frequency
of STIs was lowest (18.2%) and highest (71.4%) in age groups >= 39 and 15-20
years, respectively. Low levels of education, multiple sexual partners, lack of
knowledge on partners' STI history, and having sex under the influence of alcohol
or drugs were risk factors of for STIs (p < 0.05). We found a high prevalence of
T. vaginalis in pregnant women, with those at an early gestational age at greater
risk. The improved education of women on safe sex and the need to know partners'
STI status are advocated.
PMID- 26438602
TI - Acetylation of Histone H2AX at Lys 5 by the TIP60 Histone Acetyltransferase
Complex Is Essential for the Dynamic Binding of NBS1 to Damaged Chromatin.
AB - The association and dissociation of DNA damage response (DDR) factors with
damaged chromatin occurs dynamically, which is crucial for the activation of DDR
signaling in a spatiotemporal manner. We previously showed that the TIP60 histone
acetyltransferase complex acetylates histone H2AX, to facilitate H2AX exchange at
sites of DNA damage. However, it remained unclear how the acetylation of histone
H2AX by TIP60 is related to the DDR signaling. We found that the acetylation but
not the phosphorylation of H2AX is essential for the turnover of NBS1 on damaged
chromatin. The loss of H2AX acetylation at Lys 5 by TIP60 in cells disturbed the
accumulation of NBS1 at sites of DNA damage. Although the phosphorylation of H2AX
is also reportedly required for the retention of NBS1 at damage sites, our data
indicated that the acetylation-dependent NBS1 turnover by TIP60 on damaged
chromatin restricts the dispersal of NBS1 foci from the sites of DNA damage.
These findings indicate the importance of the acetylation-dependent dynamic
binding of NBS1 to damaged chromatin, created by histone H2AX exchange, for the
proper accumulation of NBS1 at DNA damage sites.
PMID- 26438605
TI - Potential Uses and Inherent Challenges of Using Genome-Scale Sequencing to
Augment Current Newborn Screening.
AB - Since newborn screening (NBS) began in the 1960s, technological advances have
enabled its expansion to include an increasing number of disorders. Recent
developments now make it possible to sequence an infant's genome relatively
quickly and economically. Clinical application of whole-exome and whole-genome
sequencing is expanding at a rapid pace but presents many challenges. Its utility
in NBS has yet to be demonstrated and its application in the pediatric population
requires examination, not only for potential clinical benefits, but also for the
unique ethical challenges it presents.
PMID- 26438608
TI - Corrigendum.
PMID- 26438607
TI - Aquaporins: New Targets for Cancer Therapy.
AB - Aquaporins are a family of integral membrane proteins that are expressed in all
living organisms and play vital roles in transcellular and transepithelial water
movement. Cell viability and motility are critical for progression of cancer.
Cell survival requires the suitable concentration of water and solutes. The
balance is largely maintained by aquaporins whose major function is the transport
of water and small solutes across the plasma membrane. The important role of
aquaporins has received more and more attention in the recent years. A number of
recent studies have revealed that aquaporins may be involved in cell migration
and angiogenesis. This review will highlight the expression of aquaporins in
different malignant neoplasms. Remarkably, we will summarize the influence of
drugs on aquaporins, not only the traditional Chinese medicine but also the
Western medicine. Therapeutic targeting of aquaporins may thus be advantageous
for blocking the mechanism common for a number of key cancer phenotypes.
PMID- 26438606
TI - Epigenetics and Epilepsy.
AB - Epigenetic processes in the brain involve the transfer of information arising
from short-lived cellular signals and changes in neuronal activity into lasting
effects on gene expression. Key molecular mediators of epigenetics include
methylation of DNA, histone modifications, and noncoding RNAs. Emerging findings
in animal models and human brain tissue reveal that epilepsy and epileptogenesis
are associated with changes to each of these contributors to the epigenome.
Understanding and influencing the molecular mechanisms controlling epigenetic
change could open new avenues for treatment. DNA methylation, particularly
hypermethylation, has been found to increase within gene body regions and
interference with DNA methylation in epilepsy can change gene expression profiles
and influence epileptogenesis. Posttranscriptional modification of histones,
including transient as well as sustained changes to phosphorylation and
acetylation, have been reported, which appear to influence gene expression.
Finally, roles have emerged for noncoding RNAs in brain excitability and seizure
thresholds, including microRNA and long noncoding RNA. Together, research
supports strong effects of epigenetics influencing gene expression in epilepsy,
suggesting future therapeutic approaches to manipulate epigenetic processes to
treat or prevent epilepsy.
PMID- 26438609
TI - Asna1/TRC40 Controls beta-Cell Function and Endoplasmic Reticulum Homeostasis by
Ensuring Retrograde Transport.
AB - Type 2 diabetes (T2D) is characterized by insulin resistance and beta-cell
failure. Insulin resistance per se, however, does not provoke overt diabetes as
long as compensatory beta-cell function is maintained. The increased demand for
insulin stresses the beta-cell endoplasmic reticulum (ER) and secretory pathway,
and ER stress is associated with beta-cell failure in T2D. The tail recognition
complex (TRC) pathway, including Asna1/TRC40, is implicated in the maintenance of
endomembrane trafficking and ER homeostasis. To gain insight into the role of
Asna1/TRC40 in maintaining endomembrane homeostasis and beta-cell function, we
inactivated Asna1 in beta-cells of mice. We show that Asna1(beta-/-) mice develop
hypoinsulinemia, impaired insulin secretion, and glucose intolerance that rapidly
progresses to overt diabetes. Loss of Asna1 function leads to perturbed plasma
membrane-to-trans Golgi network and Golgi-to-ER retrograde transport as well as
to ER stress in beta-cells. Of note, pharmacological inhibition of retrograde
transport in isolated islets and insulinoma cells mimicked the phenotype of
Asna1(beta-/-) beta-cells and resulted in reduced insulin content and ER stress.
These data support a model where Asna1 ensures retrograde transport and, hence,
ER and insulin homeostasis in beta-cells.
PMID- 26438610
TI - Baroreflex Sensitivity Impairment During Hypoglycemia: Implications for
Cardiovascular Control.
AB - Studies have shown associations between exposure to hypoglycemia and increased
mortality, raising the possibility that hypoglycemia has adverse cardiovascular
effects. In this study, we determined the acute effects of hypoglycemia on
cardiovascular autonomic control. Seventeen healthy volunteers were exposed to
experimental hypoglycemia (2.8 mmol/L) for 120 min. Cardiac vagal baroreflex
function was assessed using the modified Oxford method before the initiation of
the hypoglycemic-hyperinsulinemic clamp protocol and during the last 30 min of
hypoglycemia. During hypoglycemia, compared with baseline euglycemic conditions,
1) baroreflex sensitivity decreases significantly (19.2 +/- 7.5 vs. 32.9 +/- 16.6
ms/mmHg, P < 0.005), 2) the systolic blood pressure threshold for baroreflex
activation increases significantly (the baroreflex function shifts to the right;
120 +/- 14 vs. 112 +/- 12 mmHg, P < 0.005), and 3) the maximum R-R interval
response (1,088 +/- 132 vs. 1,496 +/- 194 ms, P < 0.001) and maximal range of the
R-R interval response (414 +/- 128 vs. 817 +/- 183 ms, P < 0.001) decrease
significantly. These findings indicate reduced vagal control and impaired
cardiovascular homeostasis during hypoglycemia.
PMID- 26438612
TI - RETRACTED: Simple versus branched pedal bypass in the treatment of critical limb
ischemia.
PMID- 26438611
TI - Relationship Between Left Ventricular Structural and Metabolic Remodeling in Type
2 Diabetes.
AB - Concentric left ventricular (LV) remodeling is associated with adverse
cardiovascular events and is frequently observed in patients with type 2 diabetes
mellitus (T2DM). Despite this, the cause of concentric remodeling in diabetes per
se is unclear, but it may be related to cardiac steatosis and impaired myocardial
energetics. Thus, we investigated the relationship between myocardial metabolic
changes and LV remodeling in T2DM. Forty-six nonhypertensive patients with T2DM
and 20 matched control subjects underwent cardiovascular magnetic resonance to
assess LV remodeling (LV mass-to-LV end diastolic volume ratio), function, tissue
characterization before and after contrast using T1 mapping, and (1)H and (31)P
magnetic resonance spectroscopy for myocardial triglyceride content (MTG) and
phosphocreatine-to-ATP ratio, respectively. When compared with BMI- and blood
pressure-matched control subjects, subjects with diabetes were associated with
concentric LV remodeling, higher MTG, impaired myocardial energetics, and
impaired systolic strain indicating a subtle contractile dysfunction.
Importantly, cardiac steatosis independently predicted concentric remodeling and
systolic strain. Extracellular volume fraction was unchanged, indicating the
absence of fibrosis. In conclusion, cardiac steatosis may contribute to
concentric remodeling and contractile dysfunction of the LV in diabetes. Because
cardiac steatosis is modifiable, strategies aimed at reducing MTG may be
beneficial in reversing concentric remodeling and improving contractile function
in the hearts of patients with diabetes.
PMID- 26438613
TI - Endovascular treatment of occluded and stenotic visceral vessels in patients with
chronic mesenteric ischemia.
AB - Objective Current evidence in the literature about endovascular treatment (ET) of
visceral vessels in patients with chronic mesenterial ischemia (CMI) based on
morphological characteristics is limited. The aim of this study was the
evaluation of ET in occluded and stenotic visceral vessels. Methods Patients
undergoing ET for CMI between November 2000 and November 2012 were included in
this retrospective study. Primary measure outcome was the symptom-free survival
(SFS). Secondary outcomes were primary (PPR), secondary patency (SPR) rates and
technical success rate (TSR). A Cox-regression analysis identified risk factors
for the primary and secondary measure outcomes. Results Forty patients were
included in the present study (men: 21, mean age: 68). The overall number of
vessels with intention-to-treat was 62. Fifty-two visceral arteries (18
occlusions and 34 stenoses) were successfully treated by endovascular means. The
overall TSR was 84%. Visceral vessel occlusions and atherosclerotic disease of
the superior mesenteric artery (SMA) were identified as independent risk factors
for poorer TSR ( p < 0.05). The 12-month SFS was 60%. The overall 12-month PPR
and SPR were 71% and 94%, respectively. No significant differences were observed
between occluded and stenotic vessels ( p > 0.05) concerning the PPR. On the
other hand, the subgroup analysis revealed higher SPR among occluded visceral
vessels ( p < 0.001) and coeliac axis lesions ( p < 0.001). Conclusions ET was
associated with high incidence of symptoms recurrence despite the satisfying
patency rates in both occluded and stenotic vessels. Additionally, visceral
vessel occlusion and presence of atherosclerotic lesions in the SMA were
associated with poorer TSR.
PMID- 26438617
TI - Does Type of Child Risk Affect Whether Mothers Seek Assistance for Intimate
Partner Violence From Civil or Criminal Court?
AB - We examined whether risks to children of intimate partner violence survivors
affected the type of legal assistance accessed. We hypothesized that the level
and type of perceived child risk would be associated with whether women sought a
protection order in civil court or filed charges against a current or former
intimate partner in criminal court. Using data from a sample of predominantly
African American women (N=293), we found that some forms of child risk were
positively associated with seeking a civil order of protection but negatively
associated with pressing criminal charges. Implications for practice, policy, and
future research are presented.
PMID- 26438615
TI - Storytelling in the context of vaccine refusal: a strategy to improve
communication and immunisation.
AB - The December 2014 outbreak of measles in California impacted over 100 children
and served as a reminder that this disease still plagues the USA, even 50 years
following the first licensed vaccine. Refusal of vaccination is a complicated and
multifaceted issue, one that clearly demands a closer look by paediatricians and
public health officials alike. While medical doctors and scientists are trained
to practice 'evidence-based medicine', and studies of vaccine safety and efficacy
speak the language of statistics, there is reason to believe that this is not the
most effective strategy for communicating with all groups of parents. Herein, we
consider other methods such as narrative practices that employ stories and appeal
more directly to parents. We also examine how doctors are trained to disseminate
information and whether there are reasonable supplementary methods that could be
used to improve vaccine communication and ultimately immunisation rates.
PMID- 26438614
TI - Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients
With Neonatal Diabetes Owing to Potassium Channel Mutations.
AB - OBJECTIVE: Neonatal diabetes secondary to mutations in potassium-channel subunits
is a rare disease but constitutes a paradigm for personalized genetics-based
medicine, as replacing the historical treatment with insulin injections with oral
sulfonylurea (SU) therapy has been proven beneficial. SU receptors are widely
expressed in the brain, and we therefore evaluated potential effects of SU on
neurodevelopmental parameters, which are known to be unresponsive to insulin.
RESEARCH DESIGN AND METHODS: We conducted a prospective single-center study.
Nineteen patients (15 boys aged 0.1-18.5 years) were switched from insulin to SU
therapy. MRI was performed at baseline. Before and 6 or 12 months after the
switch, patients underwent quantitative neurological and developmental
assessments and electrophysiological nerve and muscle testing. RESULTS: At
baseline, hypotonia, deficiencies in gesture conception or realization, and
attention disorders were common. SU improved HbA1c levels (median change -1.55%
[range -3.8 to 0.1]; P < 0.0001), intelligence scores, hypotonia (in 12 of 15
patients), visual attention deficits (in 10 of 13 patients), gross and fine motor
skills (in all patients younger than 4 years old), and gesture conception and
realization (in 5 of 8 older patients). Electrophysiological muscle and nerve
tests were normal. Cerebral MRI at baseline showed lesions in 12 patients,
suggesting that the impairments were central in origin. CONCLUSIONS: SU therapy
in neonatal diabetes secondary to mutations in potassium-channel subunits
produces measurable improvements in neuropsychomotor impairments, which are
greater in younger patients. An early genetic diagnosis should always be made,
allowing for a rapid switch to SU.
PMID- 26438618
TI - Neurology Resident & Fellow Section: The second decade begins.
PMID- 26438619
TI - Motor evoked potential polyphasia: A novel endophenotype of idiopathic
generalized epilepsy.
PMID- 26438621
TI - Pseudo-Foster-Kennedy syndrome with optic nerve compression by the gyrus rectus.
PMID- 26438620
TI - Anti-MOG antibodies with longitudinally extensive transverse myelitis preceded by
CLIPPERS.
PMID- 26438622
TI - Clinical Reasoning: A 68-year-old man with a history of lung cancer presenting
with right-sided weakness and aphasia.
PMID- 26438623
TI - Teaching NeuroImages: Subacute encephalopathy in a young woman with THTR2 gene
mutation.
PMID- 26438624
TI - Implantation technique of the 50-cm3 SynCardia Total Artificial Heart: does size
make a difference?
AB - Despite downsizing, implantation technique of the 50-cm(3) SynCardia Total
Artificial Heart and settings of the Companion driver remain unchanged. Owing to
the absence of de-airing nipples, de-airing procedure is even more crucial and
has to be performed carefully.
PMID- 26438625
TI - Using data envelopment analysis for assessing the performance of pediatric
emergency department physicians.
AB - In attempting to measure the performance of providers in a service industry such
as health care, it is crucial that the measurement tool recognize both the
efficiency and quality of service provided. We develop a Data Envelopment
Analysis (DEA) model to help assess the performance of emergency department (ED)
physicians at a partner hospital. The model incorporates efficiency measures as
inputs and quality measures as outputs. We demonstrate the importance of a
nuanced approach that recognizes the heterogeneity of patients that an ED
physician encounters and the important role s/he plays as a mentor for physicians
in training. In the study, patients were grouped according to their presenting
complaint and ED physicians were assessed on each group separately. Performance
variations were evident between physicians within each complaint group as well as
between groups. A secondary grouping divided patients based on whether the
attending physician was assisted by a trainee. Almost all ED physicians showed
better performance scores when not assisted by trainees or ED fellows.
PMID- 26438627
TI - Elucidating the Mechanisms of Formation for Two Unusual Cytochrome P450-Mediated
Fused Ring Metabolites of GDC-0623, a MAPK/ERK Kinase Inhibitor.
AB - Two isomeric metabolites of GDC-0623 [5-((2-fluoro-4-iodophenyl)amino)-N-(2
hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide], a mitogen-activated protein
kinase/extracellular signal-regulated kinase (MAPK/ERK) kinase inhibitor, were
identified in radiolabeled mass balance studies in rats and dogs (approximately
5% in excreta) and were also observed in human circulation (nonradiolabeled).
Mass spectrometric data indicated that both metabolites had formed a new ring
structure fused to the imidazopyridine core. Given their unusual structures, we
conducted experiments to elucidate their chemical structures and understand the
mechanisms for their formation. For the first metabolite, M14, a pyrazol-3-ol
ring was generated by N-N bond formation between the aniline and hydroxamate. For
the second metabolite, M13, an imidazol-2-one was generated by a Hofmann-type
rearrangement that involved C-C bond cleavage and C-N bond formation. Both
reactions were catalyzed by CYP2C9 and CYP2C19. M14 was generated directly from
GDC-0623 and we speculate that its formation was via oxidative activation of the
hydroxamic ester by cytochrome P450 (P450) and intramolecular nucleophilic
displacement of the ester side chain. M13 (the rearranged metabolite) formed from
the N-reduced hydroxamate (amide) and not from GDC-0623 directly. We propose for
M13 that a P450-mediated reaction formed a cationic amide intermediate, which
enabled the molecular rearrangement of the imidazopyridine core migrating from
the amide carbon to the nitrogen and subsequent cyclization reaction. Each of
these metabolic pathways constitutes a novel biotransformation mediated by P450
enzymes.
PMID- 26438626
TI - Pharmacokinetic Interactions between Drugs and Botanical Dietary Supplements.
AB - The use of botanical dietary supplements has grown steadily over the last 20
years despite incomplete information regarding active constituents, mechanisms of
action, efficacy, and safety. An important but underinvestigated safety concern
is the potential for popular botanical dietary supplements to interfere with the
absorption, transport, and/or metabolism of pharmaceutical agents. Clinical
trials of drug-botanical interactions are the gold standard and are usually
carried out only when indicated by unexpected consumer side effects or,
preferably, by predictive preclinical studies. For example, phase 1 clinical
trials have confirmed preclinical studies and clinical case reports that St.
John's wort (Hypericum perforatum) induces CYP3A4/CYP3A5. However, clinical
studies of most botanicals that were predicted to interact with drugs have shown
no clinically significant effects. For example, clinical trials did not
substantiate preclinical predictions that milk thistle (Silybum marianum) would
inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight
discrepancies between preclinical and clinical data concerning drug-botanical
interactions and critically evaluate why some preclinical models perform better
than others in predicting the potential for drug-botanical interactions. Gaps in
knowledge are also highlighted for the potential of some popular botanical
dietary supplements to interact with therapeutic agents with respect to
absorption, transport, and metabolism.
PMID- 26438628
TI - In Vitro and In Vivo Mechanistic Studies toward Understanding the Role of 1
Aminobenzotriazole in Rat Drug-Drug Interactions.
AB - 1-Aminobenzotriazole (ABT) is regularly used in vivo as a nonspecific and
irreversible cytochrome P450 inhibitor to elucidate the role of metabolism on the
pharmacokinetic profile of xenobiotics. However, few reports have considered the
recent findings that ABT can alter drug absorption or have investigated the
possible differential inhibition of ABT on intestinal and hepatic metabolism. To
address these uncertainties, pharmacokinetic studies under well controlled and
defined ABT pretreatment conditions (50 mg/kg, 1 hour ABT i.v. and 16 hours ABT
p.o.) were conducted prior to the oral administration of metoprolol, a permeable
P450 probe that undergoes extensive intestinal and hepatic metabolism. The
pharmacokinetic profile of metoprolol was affected differently by the two ABT
pretreatments. An increase in area under the curve of 16-fold with ABT p.o. and
6.5-fold with ABT i.v. was observed compared with control. Based on in vitro
studies, this difference could not be attributed to a differential inhibition of
intestinal and hepatic metabolism. In the ABT i.v. pretreatment group, the
increase in area under the curve was also associated with a prolonged time at
maximal concentration (24-fold versus control), suggesting a delay in absorption.
This was further confirmed by the administration of a charcoal meal, which
resulted in a 7-fold increase in stomach weights in the 1-hour ABT pretreated
groups compared with the untreated or 16-hour ABT pretreated rats. Based on these
results, we recommend pretreating rats with ABT p.o. 16 hours before the
administration of a test compound to preserve the inhibitory effect on intestinal
and hepatic metabolism and avoid the confounding effect on drug absorption.
PMID- 26438629
TI - The RNA-binding protein Sam68 regulates tumor cell viability and hepatic
carcinogenesis by inhibiting the transcriptional activity of FOXOs.
AB - Src associated in mitosis (Sam68; 68 kDa) is a KH domain RNA-binding protein that
belongs to the signal transduction and activation of RNA family, and has been
implicated in the oncogenesis and progression of several human cancers. Our study
aimed to investigated the clinicopathologic significance of Sam68 expression and
its role in cell proliferation and the underlying molecular mechanism in
hepatocellular carcinoma (HCC). We demonstrated that Sam68 expression was
significantly increased in HCC and high expression of Sam68 was significantly
associated with Edmondson grade, tumor size, tumor nodule number, HBsAg status
and Ki-67 expression. The Kaplan-Meier survival curves showed that increased
expression of Sam68 was correlated with poor prognosis in HCC patients and served
as an independent prognostic marker of overall survival in a multivariable
analysis. In addition, through serum starvation and refeeding assay, we
demonstrated that Sam68 was lowly expressed in serum-starved HCC cells, and was
progressively increased after serum-additioning. Furthermore, siRNA knockdown of
endogenous Sam68 inhibited cell proliferation and tumourigenicity of HCC cells in
vitro, through blocking the G1 to S phase transition. Moreover, we reported that
the anti-proliferative effect of silencing Sam68 was accompanied with up
regulated expression of cyclin-dependent kinase inhibitors, p21(Cip1) and
p27(Kip1), enhanced transactivation of FOXO factors (FOXO4), and dysreuglation of
Akt/GSK-3beta signaling. Taken together, these findings provide a rational
framework for the progression of HCC and thereby indicated that Sam68 might be a
novel and useful prognostic marker and a potential target for human HCC
treatment.
PMID- 26438630
TI - Definition, epidemiology and registries of pulmonary hypertension.
AB - Pulmonary arterial hypertension (PAH) is a subcategory of pulmonary hypertension
(PH) that comprises a group of disorders with similar pulmonary vascular
pathology. Though PH is common, the estimated incidence of IPAH is 1-3 cases per
million, making it a rare disease. The hemodynamic definition of PAH is a mean
pulmonary artery pressure at rest >OR = 25 mm Hg in the presence of a pulmonary
capillary wedge pressure =2 seizure diagnoses before age 12 months and who were also prescribed
anticonvulsants at 24 months. A child neurologist reviewed records to identify
infants who met 4 of 5 criteria for clinical Dravet syndrome: normal development
before seizure onset; >=2 seizures before age 12 months; myoclonic, hemiclonic,
or generalized tonic-clonic seizures; >=2 seizures lasting >10 minutes; and
refractory seizures after age 2 years. SCN1A gene sequencing was performed as
part of routine clinical care. RESULTS: Eight infants met the study criteria for
clinical Dravet syndrome, yielding an incidence of 1 per 15 700. Six of these
infants (incidence of 1 per 20 900) had a de novo SCN1A missense mutation that is
likely to be pathogenic. One infant had an inherited SCN1A variant that is
unlikely to be pathogenic. All 8 experienced febrile seizures, and 6 had
prolonged seizures lasting >10 minutes by age 1 year. CONCLUSIONS: Dravet
syndrome due to an SCN1A mutation is twice as common in the United States as
previously thought. Genetic testing should be considered in children with >=2
prolonged febrile seizures by 1 year of age.
PMID- 26438701
TI - Hospital Variation in Health Care Utilization by Children With Medical
Complexity.
AB - BACKGROUND: Although children with medical complexity have high health care
needs, little is known about the variation in care provided between centers. This
information may be particularly useful in identifying opportunities to improve
quality and reduce costs. METHODS: We conducted a retrospective population-based
observational cohort study using all payer claims databases for children aged 30
days to <18 years residing in Maine, New Hampshire, and Vermont from 2007 to
2010. We identified hospital-affiliated cohorts (n = 6) of patients (n = 8216)
with medical complexity by using diagnostic codes from both inpatient and
outpatient claims. Children were assigned to the hospital where they received the
most inpatient days, or their outpatient visits if no hospitalization occurred.
Outcomes of interest included patient encounters, medical imaging, and diagnostic
testing. Adjusted relative rates were calculated with overdispersed Poisson
regression models. RESULTS: Adjusting for patient characteristics, the number of
inpatient (relative rate 0.84 vs 2.28) and intensive care days (relative rate
0.45 vs 1.28) varied by more than twofold, whereas office (relative rate 0.77 vs
1.12) and emergency department visits (relative rate 0.71 vs 1.37) varied to a
lesser extent. There was also marked variation in the use of imaging, and other
diagnostic tests, with particularly high variation in electrocardiography
(relative rate 0.35 vs 2.81) and head MRI (relative rate 0.72 vs 2.12).
CONCLUSIONS: Depending on where they receive care, children with medical
complexity experience widely different patterns of utilization. These findings
indicate the need for identifying best practices for this growing patient
population.
PMID- 26438702
TI - Early Substance Use and Subsequent DUI in Adolescents.
AB - OBJECTIVE: Little is known about risk factors in early adolescence that lead to
driving under the influence (DUI) and riding with a drinking driver (RWDD). In a
diverse group of adolescents, we longitudinally explored the influence of alcohol
and marijuana (AM) use, AM beliefs, and peer and family factors (including
familism) on DUI/RWDD in high school. METHODS: We conducted 3 surveys 2 years
apart of 1189 students recruited from 16 middle schools in Southern California.
We used multivariable models to evaluate the effects of AM use, AM beliefs, and
peer and family factors at ages 12 and 14 on DUI/RWDD at age 16. RESULTS: At age
12, adolescents with more positive beliefs about marijuana (odds ratio [OR] =
1.63, 95% confidence interval [CI]: 1.20-2.20) and more ability to resist
marijuana offers (OR = 1.89, 95% CI: 1.22-2.92) had significantly higher risk of
DUI/RWDD 4 years later. At age 14, youth with more past month alcohol use (OR =
2.10, 95% CI: 1.07-4.11), positive beliefs about marijuana (OR = 1.67, 95% CI:
1.31-2.13), exposure to peer AM use (alcohol: OR = 1.01, 95% CI: 1.00-1.02;
marijuana: OR = 2.41, 95% CI: 1.28-4.53), and family marijuana use (OR = 1.54,
95% CI: 1.12-2.11) had higher risk of DUI/RWDD at age 16. CONCLUSIONS: Findings
indicate a need to target adolescents as young as sixth grade at multiple levels
to help prevent DUI/RWDD in high school. Given recent changes in legislation in
several states, research should begin to focus on the distinction between
DUI/RWDD of AM.
PMID- 26438703
TI - Effectiveness and Cost of Bidirectional Text Messaging for Adolescent Vaccines
and Well Care.
AB - OBJECTIVE: To evaluate the effectiveness and cost of bidirectional short
messaging service in increasing rates of vaccination and well child care (WCC)
among adolescents. METHODS: We included all adolescents needing a recommended
adolescent vaccine (n = 4587) whose parents had a cell-phone number in 5 private
and 2 safety-net pediatric practices. Adolescents were randomized to intervention
(n = 2228) or control (n = 2359). Parents in the intervention group received up
to 3 personalized short messaging services with response options 1 (clinic will
call to schedule), 2 (parent will call clinic), or STOP (no further short
messaging service). Primary outcomes included completion of all needed services,
WCC only, all needed vaccinations, any vaccination, and missed opportunity for
vaccination. RESULTS: Intervention patients were more likely to complete all
needed services (risk ratio [RR] 1.31, 95% confidence interval [CI] 1.12-1.53),
all needed vaccinations (RR 1.29, 95% CI 1.12-1.50), and any vaccination (RR
1.36, 95% CI 1.20-1.54). Seventy-five percent of control patients had a missed
opportunity versus 69% of intervention (P = .002). There was not a significant
difference for WCC visits. Responding that the clinic should call to schedule
("1") was associated with the highest effect size for completion of all needed
services (RR 1.89, 95% CI 1.41-2.54). Net cost ranged from $855 to $3394 per
practice. CONCLUSIONS: Bidirectional short messaging service to parents was
effective at improving rates for all adolescent vaccinations and for all needed
services, especially among parents who responded they desired a call from the
practice.
PMID- 26438705
TI - Testing for Abuse in Children With Sentinel Injuries.
AB - OBJECTIVE: Child physical abuse is commonly missed, putting abused children at
risk for repeated injury and death. Several so-called sentinel injuries have been
suggested to be associated with high rates of abuse, and to imply the need for
routine testing for other, occult traumatic injuries. Our objective was to
determine rates of abuse evaluation and diagnosis among children evaluated at
leading children's hospitals with these putative sentinel injuries. METHODS: This
is a retrospective secondary analysis of the Pediatric Health Information System
database. We identified 30 355 children with putative sentinel injuries. We
measured rates of abuse diagnosis and rates of testing commonly used to identify
occult injuries. RESULTS: Among all visits for children <24 months old to
Pediatric Health Information System hospitals, the rate of abuse diagnosis was
0.17%. Rates of abuse diagnosis for children with at least 1 putative sentinel
injury ranged from 3.5% for children <12 months old with burns to 56.1% for
children <24 months with rib fractures. Rates of skeletal survey and other
testing that can identify occult traumatic injury were highly variable between
centers and for different injuries. CONCLUSIONS: Several putative sentinel
injuries are associated with high rates of physical abuse. Among eligible
children with rib fracture(s), abdominal trauma, or intracranial hemorrhage,
rates of abuse were more than 20%. Future work is warranted to test whether
routine testing for abuse in these children can improve early recognition of
abuse.
PMID- 26438704
TI - Stigma and Parenting Children Conceived From Sexual Violence.
AB - BACKGROUND AND OBJECTIVES: Since armed conflict began in 1996, widespread sexual
violence in eastern Democratic Republic of Congo has resulted in many sexual
violence-related pregnancies (SVRPs). However, there are limited data on the
relationships between mothers and their children from sexual violence. This study
aimed to evaluate the nature and determinants of these maternal-child
relationships. METHODS: Using respondent-driven sampling, 757 women raising
children from SVRPs in South Kivu Province, Democratic Republic of Congo were
interviewed. A parenting index was created from questions assessing the maternal
child relationship. The influences of social stigma, family and community
acceptance, and maternal mental health on the parenting index were assessed in
univariate and multivariable analyses. RESULTS: The majority of mothers reported
positive attitudes toward their children from SVRPs. Prevalence of perceived
family or community stigma toward the women or their children ranged from 31.8%
to 42.9%, and prevalence of perceived family or community acceptance ranged from
45.2% to 73.5%. In multivariable analyses, stigma toward the child, as well as
maternal anxiety and depression, were associated with lower parenting indexes,
whereas acceptance of the mother or child and presence of a spouse were
associated with higher parenting indexes (all P <= .01). CONCLUSIONS: In this
study with a large sample size, stigma and mental health disorders negatively
influenced parenting attitudes, whereas family and community acceptance were
associated with adaptive parenting attitudes. Interventions to reduce
stigmatization, augment acceptance, and improve maternal mental health may
improve the long-term well-being of mothers and children from SVRPs.
PMID- 26438706
TI - Interpreting Variability in the Health Care Utilization of Children With Medical
Complexity.
PMID- 26438707
TI - Hospital Use in the Last Year of Life for Children With Life-Threatening Complex
Chronic Conditions.
AB - BACKGROUND AND OBJECTIVES: Although many adults experience resource-intensive and
costly health care in the last year of life, less is known about these health
care experiences in children with life-threatening complex chronic conditions (LT
CCCs). We assessed hospital resource use in children by type and number of LT
CCCs. METHODS: A retrospective analysis of 1252 children with LT-CCCs, ages 1 to
18 years, who died in 2012 within 40 US children's hospitals of the Pediatric
Health Information System database. LT-CCCs were identified with International
Classification of Diseases, 9th Revision, Clinical Modification codes. Using
generalized linear models, we assessed hospital admissions, days, costs, and
interventions (mechanical ventilation and surgeries) in the last year of life by
type and number of LT-CCCs. RESULTS: In the last year of life, children with LT
CCCs experienced a median of 2 admissions (interquartile range [IQR] 1-5), 27
hospital days (IQR 7-84), and $142 562 (IQR $45 270-$410 087) in hospital costs.
During the terminal admission, 76% (n = 946) were mechanically ventilated; 36% (n
= 453) underwent surgery. Hospital use was greatest (P < .001) among children
with hematologic/immunologic conditions (99 hospital days [IQR 51-146]; cost =
$504 145 [IQR $250 147-$879 331]) and children with >=3 LT-CCCs (75 hospital days
[IQR 28-132]; cost = $341 222 [IQR $146 698-$686 585]). CONCLUSIONS: Hospital use
for children with LT-CCCs in the last year of life varies significantly across
the type and number of conditions. Children with hematologic/immunologic or
multiple conditions have the greatest hospital use. This information may be
useful for clinicians striving to improve care for children with LT-CCCs nearing
the end of life.
PMID- 26438708
TI - Antenatal Three-Dimensional Printing of Aberrant Facial Anatomy.
AB - Congenital airway obstruction poses a life-threatening challenge to the newborn.
We present the first case of three-dimensional (3D) modeling and 3D printing of
complex fetal maxillofacial anatomy after prenatal ultrasound indicated potential
upper airway obstruction from a midline mass of the maxilla. Using fetal MRI and
patient-specific computer-aided modeling, the craniofacial anatomy of the fetus
was manufactured using a 3D printer. This model demonstrated the mass to be
isolated to the upper lip and maxilla, suggesting the oral airway to be patent.
The decision was made to deliver the infant without a planned ex utero
intrapartum treatment procedure. The neonate was born with a protuberant cleft
lip and palate deformity, without airway obstruction, as predicted by the patient
specific model. The delivery was uneventful, and the child was discharged without
need for airway intervention. This case demonstrates that 3D modeling may improve
prenatal evaluation of complex patient-specific fetal anatomy and facilitate the
multidisciplinary approach to perinatal management of complex airway anomalies.
PMID- 26438709
TI - Surgical Site Infection Reduction by the Solutions for Patient Safety Hospital
Engagement Network.
AB - OBJECTIVE: Surgical site infections (SSIs) negatively affect patients and the
health care system. National standards for SSI prevention do not exist in
pediatric settings. We sought to reduce SSI-related harm by implementing a
prevention bundle through the Solutions for Patient Safety (SPS) national
hospital engagement network. METHODS: Our study period was January 2011 to
December 2013. We formed a national workgroup of content and quality improvement
experts. We focused on 3 procedure types at high risk for SSIs: cardiothoracic,
neurosurgical shunt, and spinal fusion surgeries. We used the Model for
Improvement methodology and the Centers for Disease Control and Prevention SSI
definition. After literature review and consultation with experts, we distributed
a recommended bundle among network partners. Institutions were permitted to adopt
all or part of the bundle and reported local bundle adherence and SSI rates
monthly. Our learning network used webinars, discussion boards, targeted leader
messaging, and in-person learning sessions. RESULTS: Recommended bundle elements
encompassed proper preoperative bathing, intraoperative skin antisepsis, and
antibiotic delivery. Within 6 months, the network achieved 96.7% reliability
among institutions reporting adherence data. A 21% reduction in SSI rate was
reported across network hospitals, from a mean baseline rate of 2.5 SSIs per 100
procedures to a mean rate of 1.8 SSIs per 100 procedures. The reduced rate was
sustained for 15 months. CONCLUSIONS: Adoption of a SSI prevention bundle with
concomitant reliability measurement reduced the network SSI rate. Linking
reliability measurement to standardization at an institutional level may lead to
safer care.
PMID- 26438710
TI - Case Report: When an Induced Illness Looks Like a Rare Disease.
AB - The recognition of fabricated illness (FI) in a child represents a diagnostic
challenge. The suspicion of FI often arises from the discrepancy between
laboratory tests and clinical history. For instance, (unnecessary) insulin
injections by caregivers has been widely described as a common cause of
factitious hypoglycemia that may be inferred from discrepancies between plasma
insulin and c-peptide. However, contemporary administration of insulin with an
insulin secretagogue (glyburide), and of additional drugs, can make the
diagnostic pathway problematic. We report the case of a child 4 years and 11
months old, admitted for alternance of hypo- and hyperglycemia associated with
hirsutism, hypokalemia, nephrocalcinosis, and neurodevelopmental delay. All these
features were compatible with Rabson-Mendenhall syndrome, a rare disorder of
severe insulin resistance linked to mutations of insulin receptor. At admission,
plasma insulin levels were high during hypoglycemic episodes, but c-peptide was
repeatedly in the normal range. The genetic analysis of insulin receptor was
negative. The story of previous hospital admissions, inconsistency between
insulin and c-peptide values, and association between hypoglycemic episodes in
the child with the presence of the mother, raised the suspicion of FI. This
hypothesis was confirmed by a video recording that revealed the administration by
the mother of multiple drugs (insulin, glyburide, progesterone, and furosemide)
that mimicked most of the features of Rabson-Mendenhall syndrome, including
hirsutism and hypoglycemia with coincident, inappropriately normal c-peptide
values due to the administration of the insulin secretagogue. Our case indicates
that inconsistency among consecutive diagnostic tests should be regarded as a
clue of FI.
PMID- 26438711
TI - Deferred Consent for Randomized Controlled Trials in Emergency Care Settings.
AB - BACKGROUND: There is limited experience in using deferred consent for studies
involving children, which was legalized in the United Kingdom in 2008. We aimed
to inform future studies by evaluating consent rates and reasons for nonconsent
in a large randomized controlled trial in pediatric intensive care. METHODS: In
the CATCH trial, eligible children from 14 PICUs in England and Wales were
randomly assigned to 3 types of central venous catheters. To avoid delay in
treatment, children admitted on an emergency basis were first randomly assigned
to a trial central venous catheter, and we deferred seeking consent to use
already collected data and blood samples until after stabilization. RESULTS:
Consent was obtained for 984/1358 (72%) of children admitted on an emergency
basis. Failure to obtain consent resulted mainly from a lack of opportunity
(early discharge or transfer) for survivors and difficulties in seeking consent
for children who died. For admissions where there was an opportunity to approach
(n = 1298), inclusion rates differed according to survival status: 93/984 (9%) of
consented patients died, compared with 58/314 (18%) of nonconsented patients. For
children admitted on an emergency basis whose families were approached, 984/1178
(84%) provided deferred consent (n = 15 sites), compared with 441/641 (69%) of
children admitted on an elective basis who were approached for prospective
consent (n = 9 sites). CONCLUSIONS: Design of emergency randomized controlled
trials should balance the potential burden that seeking consent in difficult
situations may cause against risk of bias by disproportionately excluding
children who die or are transferred. Ethics committees could consider approving
the use of already collected data when best efforts to obtain deferred consent
are unsuccessful.
PMID- 26438712
TI - Risk Factors for Central Nervous System Tuberculosis.
AB - OBJECTIVES: To describe the epidemiology and factors associated with pediatric
central nervous system (CNS) tuberculosis (TB) in California from 1993 to 2011.
METHODS: We analyzed California TB registry data for persons aged <=18 years,
comparing CNS TB cases versus non-CNS TB cases reported from 1993 to 2011.
Factors associated with CNS TB and TB deaths were identified by using
multivariate logistic regression. RESULTS: A total of 200 CNS TB cases were
reported. Compared with non-CNS TB case patients, CNS TB case patients were more
likely to be aged <5 years (72.0% vs 43.6%; odds ratio [OR]: 3.8 [95% confidence
interval (CI): 2.4-5.9]), US-born (82.0% vs 58.2%; OR: 3.3 [CI: 2.3-4.7]), and
Hispanic (75.0% vs 63.2%; OR: 1.7 [CI: 1.3-2.4]). Among US-born CNS TB case
patients (during 2010-2011), 76.5% had a foreign-born parent. Tuberculin skin
test results were negative in 38.2% of 170 CNS TB cases tested. In multivariate
analysis, age <5 years (adjusted odds ratio [aOR]: 3.3 [CI: 2.0-5.4]), US birth
(aOR: 1.8 [CI 1.2-2.7]), and Hispanic ethnicity (aOR: 1.5 [CI: 1.1-2.1]) were
associated with an increased risk of developing CNS TB. For deaths, CNS TB (aOR:
3.8 [CI: 1.4-9.9]) and culture positivity (aOR: 6.2 [CI: 2.2-17.3]) were
associated with increased risk of death, whereas tuberculin skin test positivity
(aOR: 0.1 [CI: 0.04-0.2]) was associated with decreased risk. CONCLUSIONS:
Subsets of children are at increased risk for CNS TB in California and may
benefit from additional prevention efforts.
PMID- 26438713
TI - Taking Humanism Back to the Bedside.
PMID- 26438714
TI - Mucosal Healing in Ulcerative Colitis--When Zero is Better.
AB - BACKGROUND AND AIMS: Extensive evidence has underlined the importance of mucosal
healing as a treatment aim for ulcerative colitis (UC). We aimed to assess
differences in the incidence of clinical relapse at 12 months between UC patients
with Mayo endoscopic scores (MES) 0 and 1. METHODS: This retrospective study
included consecutive patients in corticosteroid-free remission between 2008 and
2013 and with follow-up of at least 1 year, with MES 0 or 1 in complete
colonoscopy. Clinical relapse was defined as need for induction treatment,
treatment escalation, hospitalization or surgery. A p value <0.05 was considered
statistically significant. RESULTS: The study included 138 patients, 72 (52.2%)
female, with mean age of 49 (+/-14) years. Inflammatory activity was classified
as MES 0 in 61 (44.2%) patients and MES 1 in 77 (55.8%) patients. Clinical
relapse during follow-up was significantly more frequent in patients with MES 1
than MES 0 (27.3 vs 11.5%, p = 0.022), and in the multivariate analysis MES 1 was
the only factor significantly associated with an increased risk of relapse (odds
ratio 2.89, 95% confidence interval 1.14-7.36, p = 0.026). This association was
encountered in the subgroup of patients with left-sided/extensive colitis (29.7
vs 11.1%, p = 0.049), but not proctitis (25.0 vs 12.0%, p = 0.202). CONCLUSIONS:
In patients with UC in corticosteroid-free remission, particularly those with
left-sided colitis or extensive colitis, MES 1 was significantly associated with
a 3-fold increased risk of relapse compared with endoscopic MES 0. Our results
support the use of endoscopic MES 0 as the most suitable treatment endpoint to
define mucosal healing in patients with UC.
PMID- 26438715
TI - Variability in the detection of macro TSH in different immunoassay systems.
AB - DESIGN: Macro TSH is a large molecular-sized TSH that is mostly a complex of TSH
and IgG. Patients with macro TSH have elevated serum TSH and normal free
thyroxine levels, mimicking subclinical hypothyroidism. The aim of this study was
to clarify the degree of cross-reactivity of macro TSH to different commercial
immunoassay systems. METHODS: Screening for macro TSH was done using a
polyethylene glycol (PEG) method and confirmed with gel filtration chromatography
in serum samples from 1901 patients with subclinical hypothyroidism. Interference
due to human anti-mouse antibodies (HAMA) was examined using HAMA blockers. TSH
was measured with an enzyme immunoassay for the analysis of macro TSH. Serum TSH
values in patients with macro TSH were also determined with the widely used
commercial immunoassay platforms Elecsys, Centaur and Architect, and the
detectability of macro TSH was compared among them. RESULTS: Gel filtration
chromatography was performed with 174 serum samples with PEG-precipitable TSH
ratios >75%. Twenty serum samples were found to contain large molecular-sized
TSH, five of which were due to interference by HAMA. The prevalence of macro TSH
was eventually 0.79% (15/1901). Commercial immunoassay systems variably
recognized macro TSH. The Architect TSH immunoassay platform was the least
reactive to macro TSH, but still recognized it in 60% of macro TSH-containing
serum samples. CONCLUSIONS: There were no commercial TSH immunoassay platforms
that did not cross-react with macro TSH. Screening for macro TSH should be
performed before hormone replacement therapy is initiated for subclinical
hypothyroidism.
PMID- 26438716
TI - Antioxidative Properties and Effect of Quercetin and Its Glycosylated Form
(Rutin) on Acetylcholinesterase and Butyrylcholinesterase Activities.
AB - This study sought to investigate the anticholinesterase and antioxidative
properties of quercetin and its glycosylated conjugate, rutin. The in vitro
inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)
activities, inhibition of Fe(2+)-induced lipid peroxidation in rat's brain
homogenates, radicals scavenging, and Fe(2+)-chelating abilities of the
flavonoids were investigated in vitro with concentrations of the samples ranging
from 0.06 to 0.6 mM. Quercetin had significantly higher AChE and BChE inhibitory
abilities than rutin. Quercetin also had stronger inhibition of Fe(2+)-induced
lipid peroxidation in rat's brain homogenates. Similarly, quercetin had higher
radical scavenging abilities than rutin. Quercetin also had stronger Fe(2+)
chelating ability than rutin. The inhibition of cholinesterases and antioxidative
properties are possible mechanisms by which the flavonoids can be used in the
management of oxidative stress-induced neurodegeneration.
PMID- 26438717
TI - Spread of Traditional Medicines in India: Results of National Sample Survey
Organization's Perception Survey on Use of AYUSH.
AB - For the first time, we have a comprehensive database on usage of AYUSH (acronym
for Ayurveda, naturopathy and Yoga, Unani, Siddha, and Homeopathy) in India at
the household level. This article aims at exploring the spread of the traditional
medical systems in India and the perceptions of people on the access and
effectiveness of these medical systems using this database. The article uses the
unit level data purchased from the National Sample Survey Organization, New
Delhi. Household is the basic unit of survey and the data are the collective
opinion of the household. This survey shows that less than 30% of Indian
households use the traditional medical systems. There is also a regional pattern
in the usage of particular type of traditional medicine, reflecting the regional
aspects of the development of such medical systems. The strong faith in AYUSH is
the main reason for its usage; lack of need for AYUSH and lack of awareness about
AYUSH are the main reasons for not using it. With regard to source of medicines
in the traditional medical systems, home is the main source in the Indian medical
system and private sector is the main source in Homeopathy. This shows that there
is need for creating awareness and improving access to traditional medical
systems in India. By and large, the users of AYUSH are also convinced about the
effectiveness of these traditional medicines.
PMID- 26438718
TI - The Role of Date Palm (Phoenix dactylifera L) Pollen in Fertility: A
Comprehensive Review of Current Evidence.
AB - Date palm pollen (DPP) is the male reproductive dust of palm flowers used as
dietary supplement especially as aphrodisiac and fertility enhancer in both women
and men from ancient times. Although there are few clinical trials evaluating the
beneficial effects of DPP in humans, various experimental studies have been
conducted on the reproductive effects of DPP. Among the compounds isolated from
DPP are amino acids, fatty acids, flavonoids, saponins, and estroles. The present
review summarizes comprehensive information concerning the phytochemistry and
pharmacological activities of DPP and its application in fertility disorders.
PMID- 26438719
TI - Barriers to Implementing a Reporting and Learning Patient Safety System:
Pediatric Chiropractic Perspective.
AB - A reporting and learning system is a method of monitoring the occurrence of
incidents that affect patient safety. This cross-sectional survey asked pediatric
chiropractors about factors that may limit their participation in such a system.
The list of potential barriers for participation was developed using a systematic
approach. All members of the 2 pediatric councils associated with US national
chiropractic organizations were invited to complete the survey (N = 400). The
cross-sectional survey was created using an online survey tool (REDCap) and sent
directly to member emails addressed by the respective executive committees. Of
the 400 potential respondents, 81 responded (20.3%). The most common limitations
to participating were identified as time pressure (96%) and patient concerns
(81%). Reporting and learning systems have been utilized to increase safety
awareness in many high-risk industries. To be successful, future patient safety
studies with pediatric chiropractors need to ensure these barriers are understood
and addressed.
PMID- 26438720
TI - Incorporating an Exercise Detection, Grading, and Hormone Dosing Algorithm Into
the Artificial Pancreas Using Accelerometry and Heart Rate.
AB - In this article, we present several important contributions necessary for
enabling an artificial endocrine pancreas (AP) system to better respond to
exercise events. First, we show how exercise can be automatically detected using
body-worn accelerometer and heart rate sensors. During a 22 hour overnight
inpatient study, 13 subjects with type 1 diabetes wearing a Zephyr accelerometer
and heart rate monitor underwent 45 minutes of mild aerobic treadmill exercise
while controlling their glucose levels using sensor-augmented pump therapy. We
used the accelerometer and heart rate as inputs into a validated regression
model. Using this model, we were able to detect the exercise event with a
sensitivity of 97.2% and a specificity of 99.5%. Second, from this same study, we
show how patients' glucose declined during the exercise event and we present
results from in silico modeling that demonstrate how including an exercise model
in the glucoregulatory model improves the estimation of the drop in glucose
during exercise. Last, we present an exercise dosing adjustment algorithm and
describe parameter tuning and performance using an in silico glucoregulatory
model during an exercise event.
PMID- 26438721
TI - Inhibiting myostatin signaling prevents femoral trabecular bone loss and
microarchitecture deterioration in diet-induced obese rats.
AB - Besides resulting in a dramatic increase in skeletal muscle mass, myostatin
(MSTN) deficiency has a positive effect on bone formation. However, the issue
about whether blocking MSTN can inhibit obesity-induced bone loss has not been
previously investigated. In the present study, we have evaluated the effects of
MSTN blocking on bone quality in high-fat (HF), diet-induced obese rats using a
prepared polyclonal antibody for MSTN (MsAb). Twenty-four rats were randomly
assigned to the Control, HF and HF + MsAb groups. Rats in the HF + MsAb group
were injected once a week with purified MsAb for eight weeks. The results showed
that MsAb significantly reduced body and fat weight, and increased muscle mass
and strength in the HF group. MicroCT analysis demonstrated that obesity-induced
bone loss and architecture deterioration were significantly mitigated by MsAb
treatment, as evidenced by increased bone mineral density, bone volume over total
volume, trabecular number and thickness, and decreased trabecular separation and
structure model index. However, neither HF diet nor MsAb treatment had an impact
on femoral biomechanical properties including maximum load, stiffness, energy
absorption and elastic modulus. Moreover, MsAb significantly increased
adiponectin concentrations, and decreased TNF-alpha and IL-6 levels in diet
induced obese rats. Taken together, blocking MSTN by MsAb improves bone quality
in diet-induced obese rats through a mechanotransduction pathway from skeletal
muscle, and the accompanying changes occurring in the levels of circulating
adipokines and pro-inflammatory cytokines may also be involved in this process.
It indicates that the administration of MSTN antagonists may be a promising
therapy for treating obesity and obesity-induced bone loss.
PMID- 26438722
TI - Phospholipid methylation controls Atg32-mediated mitophagy and Atg8 recycling.
AB - Degradation of mitochondria via selective autophagy, termed mitophagy,
contributes to mitochondrial quality and quantity control whose defects have been
implicated in oxidative phosphorylation deficiency, aberrant cell
differentiation, and neurodegeneration. How mitophagy is regulated in response to
cellular physiology remains obscure. Here, we show that mitophagy in yeast is
linked to the phospholipid biosynthesis pathway for conversion of
phosphatidylethanolamine to phosphatidylcholine by the two methyltransferases
Cho2 and Opi3. Under mitophagy-inducing conditions, cells lacking Opi3 exhibit
retardation of Cho2 repression that causes an anomalous increase in glutathione
levels, leading to suppression of Atg32, a mitochondria-anchored protein
essential for mitophagy. In addition, loss of Opi3 results in accumulation of
phosphatidylmonomethylethanolamine (PMME) and, surprisingly, generation of Atg8
PMME, a mitophagy-incompetent lipid conjugate of the autophagy-related ubiquitin
like modifier. Amelioration of Atg32 expression and attenuation of Atg8-PMME
conjugation markedly rescue mitophagy in opi3-null cells. We propose that proper
regulation of phospholipid methylation is crucial for Atg32-mediated mitophagy.
PMID- 26438723
TI - Alzheimer's disease-causing proline substitutions lead to presenilin 1
aggregation and malfunction.
AB - Do different neurodegenerative maladies emanate from the failure of a mutual
protein folding mechanism? We have addressed this question by comparing
mutational patterns that are linked to the manifestation of distinct
neurodegenerative disorders and identified similar neurodegeneration-linked
proline substitutions in the prion protein and in presenilin 1 that underlie the
development of a prion disorder and of familial Alzheimer's disease (fAD),
respectively. These substitutions were found to prevent the endoplasmic reticulum
(ER)-resident chaperone, cyclophilin B, from assisting presenilin 1 to fold
properly, leading to its aggregation, deposition in the ER, reduction of gamma
secretase activity, and impaired mitochondrial distribution and function.
Similarly, reduced quantities of the processed, active presenilin 1 were observed
in brains of cyclophilin B knockout mice. These discoveries imply that reduced
cyclophilin activity contributes to the development of distinct neurodegenerative
disorders, propose a novel mechanism for the development of certain fAD cases,
and support the emerging theme that this disorder can stem from aberrant
presenilin 1 function. This study also points at ER chaperones as targets for the
development of counter-neurodegeneration therapies.
PMID- 26438724
TI - H3K9 methylation extends across natural boundaries of heterochromatin in the
absence of an HP1 protein.
AB - Proteins of the conserved HP1 family are elementary components of heterochromatin
and are generally assumed to play a central role in the creation of a rigid,
densely packed heterochromatic network that is inaccessible to the transcription
machinery. Here, we demonstrate that the fission yeast HP1 protein Swi6 exists as
a single highly dynamic population that rapidly exchanges in cis and in trans
between different heterochromatic regions. Binding to methylated H3K9 or to
heterochromatic RNA decelerates Swi6 mobility. We further show that Swi6 is
largely dispensable to the maintenance of heterochromatin domains. In the absence
of Swi6, H3K9 methylation levels are maintained by a mechanism that depends on
polymeric self-association properties of Tas3, a subunit of the RNA-induced
transcriptional silencing complex. Our results disclose a surprising role for
Swi6 dimerization in demarcating constitutive heterochromatin from neighboring
euchromatin. Thus, rather than promoting maintenance and spreading of
heterochromatin, Swi6 appears to limit these processes and appropriately confine
heterochromatin.
PMID- 26438725
TI - MED23: a new Mediator of H2B monoubiquitylation.
AB - The Mediator multiprotein complex physically links transcription factors to RNA
polymerase II and the basal transcription machinery. While the Mediator complex
has been shown to be required for transcriptional initiation and elongation, the
understanding of its interplay with histone modifying enzymes and post
translational modifications remains elusive. In this issue of The EMBO Journal,
Yao et al (2015) report that the MED23 subunit of the Mediator complex physically
associates with the heterodimeric RNF20/40 E3-ligase complex to facilitate the
monoubiquitylation of histone H2B on gene bodies of actively transcribed genes.
PMID- 26438727
TI - Finding the fifth intercostal space for chest drain insertion: guidelines and
ultrasound.
AB - OBJECTIVES: International guidelines exist for chest drain insertion and
recommend identifying the fifth intercostal space or above, around the
midaxillary line. In a recent study, applying these guidelines in cadavers risked
insertion in the 6th intercostal space or below in 80% of cases. However, there
are limitations of cadaveric studies and this investigation uses ultrasound to
determine the intercostal space identified when applying these guidelines in
healthy adult volunteers. METHODS: On each side of the chest wall in 31
volunteers, the position for drain insertion was identified using the European
Trauma Course method, Advanced Trauma Life Support (ATLS) method, British
Thoracic Society's 'safe triangle' and the 'traditional' method of palpation.
Ultrasound imaging was used to determine the relationship of the skin marks with
the underlying intercostal spaces. RESULTS: Five methods were assessed on 60
sides. In contrast to the cadaveric study, 94% of skin marks lay over a safe
intercostal space. However, the range of intercostal spaces found spanned the
second to the seventh space. In 44% of women, the inferior boundary of the 'safe
triangle' and the ATLS guidelines located the sixth intercostal space or below.
CONCLUSIONS: Current guidelines often identify a safe site for chest drain
insertion, although the same site is not reproducibly found. In addition, women
appear to be at risk of subdiaphragmatic drain insertion when the nipple is used
to identify the fifth intercostal space. Real-time ultrasonography can be used to
confirm the intercostal space during this procedure, although a safe guideline is
still needed for circumstances in which ultrasound is not possible.
PMID- 26438726
TI - The balance of Id3 and E47 determines neural stem/precursor cell differentiation
into astrocytes.
AB - Adult neural stem/precursor cells (NSPCs) of the subventricular zone (SVZ) are an
endogenous source for neuronal replacement in CNS disease. However, adult
neurogenesis is compromised after brain injury in favor of a glial cell fate,
which is mainly attributed to changes in the NSPC environment. Yet, it is unknown
how this unfavorable extracellular environment translates into a transcriptional
program altering NSPC differentiation. Here, we show that genetic depletion of
the transcriptional regulator Id3 decreased the number of astrocytes generated
from SVZ-derived adult NSPCs in the cortical lesion area after traumatic brain
injury. Cortical brain injury resulted in rapid BMP-2 and Id3 up-regulation in
the SVZ stem cell niche. Id3(-/-) adult NSPCs failed to differentiate into BMP-2
induced astrocytes, while NSPCs deficient for the Id3-controlled transcription
factor E47 readily differentiated into astrocytes in the absence of BMP-2.
Mechanistically, E47 repressed the expression of several astrocyte-specific genes
in adult NSPCs. These results identify Id3 as the BMP-2-induced transcriptional
regulator, promoting adult NSPC differentiation into astrocytes upon CNS injury
and reveal a molecular link between environmental changes and NSPC
differentiation in the CNS after injury.
PMID- 26438728
TI - Celecoxib reduces glucocorticoids in vitro and in a mouse model with
adrenocortical hyperplasia.
AB - Primary pigmented nodular adrenocortical disease (PPNAD), whether in the context
of Carney complex (CNC) or isolated, leads to ACTH-independent Cushing's syndrome
(CS). CNC and PPNAD are caused typically by inactivating mutations of PRKAR1A, a
gene coding for the type 1a regulatory subunit (R1alpha) of cAMP-dependent
protein kinase (PKA). Mice lacking Prkar1a, specifically in the adrenal cortex
(AdKO) developed CS caused by bilateral adrenal hyperplasia (BAH), which is
formed from the abnormal proliferation of fetal-like adrenocortical cells.
Celecoxib is a cyclooxygenase 2 (COX2) inhibitor. In bone, Prkar1a inhibition is
associated with COX2 activation and prostaglandin E2 (PGE2) production that, in
turn, activates proliferation of bone stromal cells. We hypothesized that COX2
inhibition may have an effect in PPNAD. In vitro treatment of human cell lines,
including one from a patient with PPNAD, with celecoxib resulted in decreased
cell viability. We then treated AdKO and control mice with 1500 mg/kg celecoxib
or vehicle. Celecoxib treatment led to decreased PGE2 and corticosterone levels,
reduced proliferation and increased apoptosis of adrenocortical cells, and
decreased steroidogenic gene expression. We conclude that, in vitro and in vivo,
celecoxib led to decreased steroidogenesis. In a mouse model of PPNAD, celecoxib
caused histological changes that, at least in part, reversed BAH and this was
associated with a reduction of corticosterone levels.
PMID- 26438730
TI - Subtle modulation of ongoing calcium dynamics in astrocytic microdomains by
sensory inputs.
AB - Astrocytes communicate with neurons through their processes. In vitro experiments
have demonstrated that astrocytic processes exhibit calcium activity both
spontaneously and in response to external stimuli; however, it has not been fully
determined whether and how astrocytic subcellular domains respond to sensory
input in vivo. We visualized the calcium signals in astrocytes in the primary
visual cortex of awake, head-fixed mice. Bias-free analyses of two-photon imaging
data revealed that calcium activity prevailed in astrocytic subcellular domains,
was coordinated with variable spot-like patterns, and was dominantly spontaneous.
Indeed, visual stimuli did not affect the frequency of calcium domain activity,
but it increased the domain size, whereas tetrodotoxin reduced the sizes of
spontaneous calcium domains and abolished their visual responses. The "evoked"
domain activity exhibited no apparent orientation tuning and was distributed
unevenly within the cell, constituting multiple active hotspots that were often
also recruited in spontaneous activity. The hotspots existed dominantly in the
somata and endfeet of astrocytes. Thus, the patterns of astrocytic calcium
dynamics are intrinsically constrained and are subject to minor but significant
modulation by sensory input.
PMID- 26438731
TI - Renal stromal miRNAs are required for normal nephrogenesis and glomerular
mesangial survival.
AB - MicroRNAs are small noncoding RNAs that post-transcriptionally regulate mRNA
levels. While previous studies have demonstrated that miRNAs are indispensable in
the nephron progenitor and ureteric bud lineage, little is understood about
stromal miRNAs during kidney development. The renal stroma (marked by expression
of FoxD1) gives rise to the renal interstitium, a subset of peritubular
capillaries, and multiple supportive vascular cell types including pericytes and
the glomerular mesangium. In this study, we generated FoxD1(GC);Dicer(fl/fl)
transgenic mice that lack miRNA biogenesis in the FoxD1 lineage. Loss of Dicer
activity resulted in multifaceted renal anomalies including perturbed
nephrogenesis, expansion of nephron progenitors, decreased renin-expressing
cells, fewer smooth muscle afferent arterioles, and progressive mesangial cell
loss in mature glomeruli. Although the initial lineage specification of FoxD1(+)
stroma was not perturbed, both the glomerular mesangium and renal interstitium
exhibited ectopic apoptosis, which was associated with increased expression of
Bcl2l11 (Bim) and p53 effector genes (Bax, Trp53inp1, Jun, Cdkn1a, Mmp2, and
Arid3a). Using a combination of high-throughput miRNA profiling of the FoxD1(+)
derived cells and mRNA profiling of differentially expressed transcripts in
FoxD1(GC);Dicer(fl/fl) kidneys, at least 72 miRNA:mRNA target interactions were
identified to be suppressive of the apoptotic program. Together, the results
support an indispensable role for stromal miRNAs in the regulation of apoptosis
during kidney development.
PMID- 26438729
TI - Immunity and immune modulation in Trypanosoma cruzi infection.
AB - Chagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches
the secondary lymphoid organs, the heart, skeletal muscles, neurons in the
intestine and esophagus among other tissues. The disease is characterized by mega
syndromes, which may affect the esophagus, the colon and the heart, in about 30%
of infected people. The clinical manifestations associated with T. cruzi
infection during the chronic phase of the disease are dependent on complex
interactions between the parasite and the host tissues, particularly the lymphoid
system that may either result in a balanced relationship with no disease or in an
unbalanced relationship that follows an inflammatory response to parasite
antigens and associated tissues in some of the host organs and/or by an
autoimmune response to host antigens. This review discusses the findings that
support the notion of an integrated immune response, considering the innate and
adaptive arms of the immune system in the control of parasite numbers and also
the mechanisms proposed to regulate the immune response in order to tolerate the
remaining parasite load, during the chronic phase of infection. This knowledge is
fundamental to the understanding of the disease progression and is essential for
the development of novel therapies and vaccine strategies.
PMID- 26438734
TI - Erratum.
PMID- 26438732
TI - The effects of intragastric infusion of umami solutions on amygdalar and lateral
hypothalamic neurons in rats.
AB - Previous behavioral studies have suggested that l-glutamate, an umami substance,
is detected in the gut, and that this information regarding glutamate is conveyed
from the gut to the amygdala and the lateral hypothalamus (LH) through the vagus
nerve to establish glutamate preference. In this study, we investigated the roles
of the amygdala and LH in the information processing of gut glutamate. We
recorded the activity of amygdalar and LH neurons during the intragastric
administration of five test solutions (monosodium l-glutamate [MSG, 60 mmol/L];
inosine monophosphate [IMP, 60 mmol/L]; a mixture of MSG and IMP; NaCl [60
mmol/L]; or physiological saline) in intact and subdiaphragmatic vagotomized
awake rats. In intact rats, 349 and 189 neurons were recorded from the amygdala
and LH, respectively, while in vagotomized rats, 104 and 90 neurons were recorded
from the amygdala and LH, respectively. In intact rats, similar percentages of
neurons (30-60%) in the amygdala and LH responded to the intragastric infusion of
the solutions. Vagotomy significantly altered responses to the MSG and NaCl
solutions. In particular, vagotomy suppressed the inhibitory responses to the
NaCl solution. Furthermore, vagotomy increased the response similarity between
the MSG and NaCl solutions, suggesting that vagotomy impaired the coding of the
postingestive consequences of the MSG solution in the amygdala and LH, which are
unique for glutamate. The present results provide the first neurophysiological
evidence that amygdalar and LH neurons process glutamate signals from the gut.
PMID- 26438735
TI - The Interplay Between Health And Social Supports.
PMID- 26438733
TI - PGC-1 isoforms and their target genes are expressed differently in human skeletal
muscle following resistance and endurance exercise.
AB - The primary aim of the present study was to investigate the acute gene expression
responses of PGC-1 isoforms and PGC-1alpha target genes related to mitochondrial
biogenesis (cytochrome C), angiogenesis (VEGF-A), and muscle hypertrophy
(myostatin), after a resistance or endurance exercise bout. In addition, the
study aimed to elucidate whether the expression changes of studied transcripts
were linked to phosphorylation of AMPK and MAPK p38. Nineteen physically active
men were divided into resistance exercise (RE, n = 11) and endurance exercise
(EE, n = 8) groups. RE group performed leg press exercise (10 * 10 RM, 50 min)
and EE walked on a treadmill (~80% HRmax, 50 min). Muscle biopsies were obtained
from the vastus lateralis muscle before, 30 min, and 180 min after exercise. EE
and RE significantly increased the gene expression of alternative promoter
originated PGC-1alpha exon 1b- and 1bxs'-derived isoforms, whereas the proximal
promoter originated exon 1a-derived transcripts were less inducible and were
upregulated only after EE. Truncated PGC-1alpha transcripts were upregulated both
after EE and RE. Neither RE nor EE affected the expression of PGC-1beta. EE
upregulated the expression of cytochrome C and VEGF-A, whereas RE upregulated
VEGF-A and downregulated myostatin. Both EE and RE increased the levels of p-AMPK
and p-MAPK p38, but these changes were not linked to the gene expression
responses of PGC-1 isoforms. The present study comprehensively assayed PGC-1
transcripts in human skeletal muscle and showed exercise mode-specific responses
thus improving the understanding of early signaling events in exercise-induced
muscle adaptations.
PMID- 26438736
TI - An Overdose Antidote Goes Mainstream.
PMID- 26438737
TI - Connecticut's 'Money Follows The Person' Yields Positive Results For
Transitioning People Out Of Institutions.
AB - A centerpiece of federal and state efforts to rebalance long-term services and
supports to enhance consumer choice and contain costs, the federal Money Follows
the Person Rebalancing Demonstration helps qualified individuals living in
institutions make the transition to life in the community. The Connecticut Money
Follows the Person program is an unusually rich source of data, with information
on the 2,262 people who transitioned to the community under that state's program
during 2008-14. Responses to participant surveys completed before and six,
twelve, and twenty-four months after transition indicate that, for the majority
of respondents who remained in the community, quality of life and life
satisfaction improved significantly after transition, and they stayed high. About
half of the participants visited hospitals or emergency departments after
transition; however, only 14 percent had returned to an institution one year
after transition. Predictors of reinstitutionalization included some not
previously observed: mental health disability, difficulties with family members
before transition, and not exercising choice and control in daily life. These and
other findings suggest multiple ways in which policy makers can target efforts to
strengthen transition programs that can meaningfully improve people's lives while
containing costs.
PMID- 26438738
TI - US Prevalence And Predictors Of Informal Caregiving For Dementia.
PMID- 26438739
TI - The Disproportionate Impact Of Dementia On Family And Unpaid Caregiving To Older
Adults.
AB - The number of US adults ages sixty-five and older who are living with dementia is
substantial and expected to grow, raising concerns about the demands that will be
placed on family members and other unpaid caregivers. We used data from the 2011
National Health and Aging Trends Study and its companion study, the National
Study of Caregiving, to investigate the role of dementia in caregiving. We found
that among family and unpaid caregivers to older noninstitutionalized adults, one
third of caregivers, and 41 percent of the hours of help they provide, help
people with dementia, who account for about 10 percent of older
noninstitutionalized adults. Among older adults who receive help, the vast
majority in both community and residential care settings other than nursing homes
rely on family or unpaid caregivers (more than 90 percent and more than 80
percent, respectively), regardless of their dementia status. Caregiving is most
intense, however, to older adults with dementia in community settings and from
caregivers who are spouses or daughters or who live with the care recipient.
PMID- 26438740
TI - Integrated Payment And Delivery Models Offer Opportunities And Challenges For
Residential Care Facilities.
AB - Under health care reform, new financing and delivery models are being piloted to
integrate health and long-term care services for older adults. Programs using
these models generally have not included residential care facilities. Instead,
most of them have focused on long-term care recipients in the community or the
nursing home. Our analyses indicate that individuals living in residential care
facilities have similarly high rates of chronic illness and Medicare utilization
when compared with matched individuals in the community and nursing home, and
rates of functional dependency that fall between those of their counterparts in
the other two settings. These results suggest that the residential care facility
population could benefit greatly from models that coordinated health and long
term care services. However, few providers have invested in the infrastructure
needed to support integrated delivery models. Challenges to greater care
integration include the private-pay basis for residential care facility services,
which precludes shared savings from reduced Medicare costs, and residents'
preference for living in a home-like, noninstitutional environment.
PMID- 26438741
TI - Nearly Half Of US Adults Living With HIV Received Federal Disability Benefits In
2009.
AB - The effects of HIV infection on national labor-force participation have not been
rigorously evaluated. Using data from the Medical Monitoring Project and the
National Health Interview Survey, we present nationally representative estimates
of the receipt of disability benefits by adults living with HIV receiving care
compared with the general US adult population. We found that in 2009, adults
living with HIV were nine times more likely than adults in the general population
to receive disability benefits. The risk of being on disability is also greater
for younger and more educated adults living with HIV compared to the general
population, which suggests that productivity losses can result from HIV
infection. To prevent disability, early diagnosis and treatment of HIV are
essential. This study offers a baseline against which to measure the impacts of
recently proposed or enacted changes to Medicaid and private insurance markets,
including the Affordable Care Act and proposed revisions to the Social Security
Administration's HIV Infection Listings.
PMID- 26438742
TI - Broad Hepatitis C Treatment Scenarios Return Substantial Health Gains, But
Capacity Is A Concern.
AB - Treatment of hepatitis C virus, the most common chronic viral infection in the
United States, has historically suffered from challenges including serious side
effects, low efficacy, and ongoing transmission and reinfection. Recent
innovations have produced breakthrough therapies that are effective in more than
90 percent of patients. These treatments could dramatically reduce the virus's
prevalence but are costly. To quantify the benefit of these treatments to
society, including the value of reduced transmission, we estimated the effects of
several hepatitis C treatment strategies on cost and population health. Treating
patients at all disease stages could generate $610-$1,221 billion in additional
quality-adjusted life-years, plus an additional $139 billion in saved medical
expenditures over fifty years, and minimize the disease burden, but up-front
treatment costs would exceed $150 billion. An intermediate scenario--treating 5
percent of the infected population annually, regardless of patients' disease
stages--would also return substantial benefits and would be much more affordable
under current financing schemes.
PMID- 26438744
TI - Medicare's Part D Drug Benefit At 10 Years: Firmly Established But Still
Evolving.
PMID- 26438743
TI - High-Cost Patients Had Substantial Rates Of Leaving Medicare Advantage And
Joining Traditional Medicare.
AB - Medicare Advantage payment regulations include risk-adjusted capitated
reimbursement, which was implemented to discourage favorable risk selection and
encourage the retention of members who incur high costs. However, the extent to
which risk-adjusted capitation has succeeded is not clear, especially for members
using high-cost services not previously considered in assessments of risk
selection. We examined the rates at which participants who used three high-cost
services switched between Medicare Advantage and traditional Medicare. We found
that the switching rate from 2010 to 2011 away from Medicare Advantage and to
traditional Medicare exceeded the switching rate in the opposite direction for
participants who used long-term nursing home care (17 percent versus 3 percent),
short-term nursing home care (9 percent versus 4 percent), and home health care
(8 percent versus 3 percent). These results were magnified among people who were
enrolled in both Medicare and Medicaid. Our findings raise questions about the
role of Medicare Advantage plans in serving high-cost patients with complex care
needs, who account for a disproportionately high amount of total health care
spending.
PMID- 26438745
TI - California's Early ACA Expansion Increased Coverage And Reduced Out-Of-Pocket
Spending For The State's Low-Income Population.
AB - The Affordable Care Act (ACA) expanded eligibility for Medicaid to millions of
low-income adults. While many expanding states implemented their expansion in
2014, five states and the District of Columbia expanded eligibility as early as
2010 by taking advantage of provisions in the ACA and Medicaid waivers. We used
restricted data from the National Health Interview Survey to examine the impact
of California's Low Income Health Program, an early expansion program that began
in 2011. Our study demonstrates that the county-by-county rollout of expanded
public insurance coverage in California significantly increased coverage, by 7
percentage points, and significantly reduced the likelihood of any family out-of
pocket medical spending in the previous year, by 10 percentage points, among low
income adults.
PMID- 26438746
TI - Out-Of-Pocket Prescription Costs Under A Typical Silver Plan Are Twice As High As
They Are In The Average Employer Plan.
AB - The health insurance Marketplaces created under the Affordable Care Act have
attracted nearly ten million enrollees, including many people who were previously
insured by an employer-sponsored plan. The most popular Marketplace plan--the
silver plan--has significantly higher cost sharing than does a typical employer
sponsored plan, which may cause patients to reduce the use of cost-saving
services that are essential for managing chronic conditions. We estimated the
impact of higher cost sharing on drug and medical spending among patients with
chronic conditions. Using national data, we compared cost sharing and
prescription and medical spending for patients covered by employer-sponsored
plans to the spending for those in a typical silver plan in the Marketplaces. Our
results show that out-of-pocket expenses for medications in a typical silver plan
are twice as high as they are in the average employer-sponsored plan, resulting
in fewer prescriptions filled and refilled and in higher spending on other
medical services. Maintaining the use of cost-effective prescription medications
might require lower cost sharing for patients with chronic conditions than is
currently found in the Marketplaces.
PMID- 26438747
TI - Assessing Latin America's Progress Toward Achieving Universal Health Coverage.
AB - Two commonly used metrics for assessing progress toward universal health coverage
involve assessing citizens' rights to health care and counting the number of
people who are in a financial protection scheme that safeguards them from high
health care payments. On these metrics most countries in Latin America have
already "reached" universal health coverage. Neither metric indicates, however,
whether a country has achieved universal health coverage in the now commonly
accepted sense of the term: that everyone--irrespective of their ability to pay-
gets the health services they need without suffering undue financial hardship. We
operationalized a framework proposed by the World Bank and the World Health
Organization to monitor progress under this definition and then constructed an
overall index of universal health coverage achievement. We applied the approach
using data from 112 household surveys from 1990 to 2013 for all twenty Latin
American countries. No country has achieved a perfect universal health coverage
score, but some countries (including those with more integrated health systems)
fare better than others. All countries except one improved in overall universal
health coverage over the time period analyzed.
PMID- 26438748
TI - Risk Selection Threatens Quality Of Care For Certain Patients: Lessons From
Europe's Health Insurance Exchanges.
AB - Experience in European health insurance exchanges indicates that even with the
best risk-adjustment formulas, insurers have substantial incentives to engage in
risk selection. The potentially most worrisome form of risk selection is skimping
on the quality of care for underpriced high-cost patients--that is, patients for
whom insurers are compensated at a rate lower than the predicted health care
expenses of these patients. In this article we draw lessons for the United States
from twenty years of experience with health insurance exchanges in Europe, where
risk selection is a serious problem. Mistakes by European legislators and
inadequate evaluation criteria for risk selection incentives are discussed, as
well as strategies to reduce risk selection and the complex trade-off among
selection (through quality skimping), efficiency, and affordability. Recommended
improvements to the risk-adjustment process in the United States include
considering the adoption of risk adjusters used in Europe, investing in the
collection of data, using a permanent form of risk sharing, and replacing the
current premium "band" restrictions with more flexible restrictions. Policy
makers need to understand the complexities of regulating competitive health
insurance markets and to prevent risk selection that threatens the provision of
good-quality care for underpriced high-cost patients.
PMID- 26438749
TI - Uncompensated Care Burden May Mean Financial Vulnerability For Rural Hospitals In
States That Did Not Expand Medicaid.
AB - The implementation of the Affordable Care Act has led to a large decrease in the
number of uninsured people. Yet uncompensated care will still occur, particularly
in states where eligibility for Medicaid is not expanded. We compared rural
hospitals in Medicaid expansion and nonexpansion states in terms of the amount of
uncompensated care they provided and their profitability and market
characteristics in 2013. We found that rural hospitals in expansion states
provided more dollars of uncompensated care than those in nonexpansion states and
that the difference was at least partly driven by greater uncompensated costs
associated with public programs such as Medicaid. We found higher dollar values
of unrecoverable debt and charity care among non-critical access rural hospitals
in nonexpansion states than among those in expansion states. Compared to
hospitals in expansion states, those in nonexpansion states provided greater
amounts of uncompensated care as a percentage of revenues and appeared to be more
financially vulnerable; thus, these hospitals may be more likely to experience
financial pressure or losses. Policy makers need to formulate strategies for
maintaining access to care for rural populations residing in nonexpansion states.
PMID- 26438750
TI - Observation Rates At Veterans' Hospitals More Than Doubled During 2005-13,
Similar To Medicare Trends.
AB - When neither inpatient admission nor prompt discharge is clearly indicated for a
patient in the emergency department, physicians place the patient under
observation in a hospital for diagnosis and treatment. The increasing prevalence
of observation stays at hospitals reimbursed by Medicare is receiving
considerable attention, but the prevalence remains unexplored in Veterans Health
Administration (VHA) hospitals, which are subject to different payment policies.
Using VHA data for fiscal years 2005-13, we identified trends and variations in
observation rates across twenty-one Veteran Integrated Service Networks and 128
VHA hospitals nationwide. We found that observation rates across VHA hospitals
more than doubled, from 6.5 percent to 13.8 percent, and that there was
substantial variation across both Veteran Integrated Service Networks and
hospitals. The most prevalent diagnoses accounted for an increasing share of
observation stays over time. Despite different incentives within the VHA and
Medicare, rates of observation have increased over time for both populations.
PMID- 26438751
TI - Price Increases Were Much Lower In Ambulatory Surgery Centers Than Hospital
Outpatient Departments In 2007-12.
AB - Ambulatory surgery centers (ASCs) are freestanding facilities that provide
services to patients who do not require an overnight stay. The number of ASCs has
grown rapidly over the past fifteen years, as have the number of surgical
procedures performed at them. ASCs now compete with hospital outpatient
departments. This study examined the revenue side of ASC growth by using a large
national claims database that contains information on actual prices paid. For six
common outpatient surgical procedures, prices paid to ASCs on the whole grew in
line with general medical care prices, while overall prices paid to hospital
outpatient departments for the same procedures climbed sharply. This provides no
evidence that ASCs are successfully pressuring hospital outpatient departments to
lower their prices. Not unexpectedly, private insurers paid ASCs considerably
more than Medicare paid ASCs for the same procedures. Medicare currently pays
ASCs a legislated percentage of what it pays hospital outpatient departments for
the same services, but there is a considerable discrepancy between this ratio and
the ratio of payments by private insurers across provider types and procedures.
This finding questions the wisdom of using a single ratio for ASC payments to
hospital outpatient department payments.
PMID- 26438752
TI - Payment Reform Pilot In Beijing Hospitals Reduced Expenditures And Out-Of-Pocket
Payments Per Admission.
AB - In 2009 China announced plans to reform provider payment methods at public
hospitals by moving from fee-for-service (FFS) to prospective and aggregated
payment methods that included the use of diagnosis-related groups (DRGs) to
control health expenditures. In October 2011 health policy makers selected six
Beijing hospitals to pioneer the first DRG payment system in China. We used
hospital discharge data from the six pilot hospitals and eight other hospitals,
which continued to use FFS and served as controls, from the period 2010-12 to
evaluate the pilot's impact on cost containment through a difference-in
differences methods design. Our study found that DRG payment led to reductions of
6.2 percent and 10.5 percent, respectively, in health expenditures and out-of
pocket payments by patients per hospital admission. We did not find evidence of
any increase in hospital readmission rates or cost shifting from cases eligible
for DRG payment to ineligible cases. However, hospitals continued to use FFS
payments for patients who were older and had more complications than other
patients, which reduced the effectiveness of payment reform. Continuous evidence
based monitoring and evaluation linked with adequate management systems are
necessary to enable China and other low- and middle-income countries to broadly
implement DRGs and refine payment systems.
PMID- 26438753
TI - Less Physician Practice Competition Is Associated With Higher Prices Paid For
Common Procedures.
AB - Concentration among physician groups has been steadily increasing, which may
affect prices for physician services. We assessed the relationship in 2010
between physician competition and prices paid by private preferred provider
organizations for fifteen common, high-cost procedures to understand whether
higher concentration of physician practices and accompanying increased market
power were associated with higher prices for services. Using county-level
measures of the concentration of physician practices and county average prices,
and statistically controlling for a range of other regional characteristics, we
found that physician practice concentration and prices were significantly
associated for twelve of the fifteen procedures we studied. For these procedures,
counties with the highest average physician concentrations had prices 8-26
percent higher than prices in the lowest counties. We concluded that physician
competition is frequently associated with prices. Policies that would influence
physician practice organization should take this into consideration.
PMID- 26438754
TI - Exposure To Harmful Workplace Practices Could Account For Inequality In Life
Spans Across Different Demographic Groups.
AB - The existence of important socioeconomic disparities in health and mortality is a
well-established fact. Many pathways have been adduced to explain inequality in
life spans. In this article we examine one factor that has been somewhat
neglected: People with different levels of education get sorted into jobs with
different degrees of exposure to workplace attributes that contribute to poor
health. We used General Social Survey data to estimate differential exposures to
workplace conditions, results from a meta-analysis that estimated the effect of
workplace conditions on mortality, and a model that permitted us to estimate the
overall effects of workplace practices on health. We conclude that 10-38 percent
of the difference in life expectancy across demographic groups can be explained
by the different job conditions their members experience.
PMID- 26438755
TI - Lesbian, Gay, And Bisexual Adults Making Gains In Health Insurance And Access To
Care.
PMID- 26438759
TI - The Safety Net: How Foundations Are Supporting It.
PMID- 26438762
TI - Negative Ads: The Authors Reply.
PMID- 26438761
TI - Negative Ads And Smoking Prevalence.
PMID- 26438763
TI - Left Ventricular Assist Devices.
PMID- 26438764
TI - Left Ventricular Assist Devices: The Authors Reply.
PMID- 26438765
TI - Hospitals' Charity Care.
PMID- 26438766
TI - Hospitals' Charity Care: The Authors Reply.
PMID- 26438767
TI - Tax Exemptions For Nonprofit Hospitals.
PMID- 26438768
TI - Cardiovascular Management in Pregnancy: Antithrombotic Agents and Antiplatelet
Agents.
PMID- 26438769
TI - ECG Response: October 6, 2015.
PMID- 26438770
TI - Image Fusion Guided Device Closure of Left Ventricle to Right Atrium Shunt.
PMID- 26438771
TI - Right Ventricular Hypertrophy Along With Malignant Ventricular Arrhythmias: An
Uncommon Case of Sarcoidosis at Cardiac Magnetic Resonance Imaging.
PMID- 26438772
TI - Cardiology Patient Page. Magnetic Resonance Imaging in Patients With Cardiac
Implantable Electronic Devices.
PMID- 26438773
TI - Letter by Lavine Regarding Article, "Cardiovascular, Bleeding, and Mortality
Risks in Elderly Medicare Patients Treated With Dabigatran or Warfarin for
Nonvalvular Atrial Fibrillation".
PMID- 26438774
TI - Letter by Wheeler et al Regarding Article, "Recognition and Significance of
Pathological T-Wave Inversions in Athletes".
PMID- 26438775
TI - Response to Letter Regarding Article, "Recognition and Significance of
Pathological T-Wave Inversions in Athletes".
PMID- 26438776
TI - Letter by Almendro-Delia et al Regarding Article, "Association Between Surgical
Indications, Operative Risk, and Clinical Outcome in Infective Endocarditis: A
Prospective Study From the International Collaboration on Endocarditis".
PMID- 26438777
TI - Response to Letter Regarding Article, "Association Between Surgical Indications,
Operative Risk, and Clinical Outcome in Infective Endocarditis: A Prospective
Study From the International Collaboration on Endocarditis".
PMID- 26438778
TI - Letter by Barison et al Regarding Article, "Familial Clustering of Mitral Valve
Prolapse in the Community".
PMID- 26438779
TI - Response to Letter Regarding Article, "Familial Clustering of Mitral Valve
Prolapse in the Community".
PMID- 26438780
TI - Pneumonia's second wind? A case study of the global health network for childhood
pneumonia.
AB - Advocacy, policy, research and intervention efforts against childhood pneumonia
have lagged behind other health issues, including malaria, measles and
tuberculosis. Accelerating progress on the issue began in 2008, following decades
of efforts by individuals and organizations to address the leading cause of
childhood mortality and establish a global health network. This article traces
the history of this network's formation and evolution to identify lessons for
other global health issues. Through document review and interviews with current,
former and potential network members, this case study identifies five distinct
eras of activity against childhood pneumonia: a period of isolation (post WWII to
1984), the duration of WHO's Acute Respiratory Infections (ARI) Programme (1984
1995), Integrated Management of Childhood illness's (IMCI) early years (1995
2003), a brief period of network re-emergence (2003-2008) and recent accelerating
progress (2008 on). Analysis of these eras reveals the critical importance of
building a shared identity in order to form an effective network and take
advantage of emerging opportunities. During the ARI era, an initial network
formed around a relatively narrow shared identity focused on community-level
care. The shift to IMCI led to the partial dissolution of this network, stalled
progress on addressing pneumonia in communities and missed opportunities.
Frustrated with lack of progress on the issue, actors began forming a network and
shared identity that included a broad spectrum of those whose interests overlap
with pneumonia. As the network coalesced and expanded, its members coordinated
and collaborated on conducting and sharing research on severity and tractability,
crafting comprehensive strategies and conducting advocacy. These network
activities exerted indirect influence leading to increased attention, funding,
policies and some implementation.
PMID- 26438781
TI - Dose-Response Relationship Between Physical Activity and Risk of Heart Failure: A
Meta-Analysis.
AB - BACKGROUND: Prior studies have reported an inverse association between physical
activity (PA) and risk of heart failure (HF). However, a comprehensive assessment
of the quantitative dose-response association between PA and HF risk has not been
reported previously. METHODS AND RESULTS: Prospective cohort studies with
participants >18 years of age that reported association of baseline PA levels and
incident HF were included. Categorical dose-response relationships between PA and
HF risk were assessed with random-effects models. Generalized least-squares
regression models were used to assess the quantitative relationship between PA
(metabolic equivalent [MET]-min/wk) and HF risk across studies reporting
quantitative PA estimates. Twelve prospective cohort studies with 20 203 HF
events among 370 460 participants (53.5% women; median follow-up, 13 years) were
included. The highest levels of PA were associated with significantly reduced
risk of HF (pooled hazard ratio for highest versus lowest PA, 0.70; 95%
confidence interval, 0.67-0.73). Compared with participants reporting no leisure
time PA, those who engaged in guideline-recommended minimum levels of PA (500 MET
min/wk; 2008 US federal guidelines) had modest reductions in HF risk (pooled
hazard ratio, 0.90; 95% confidence interval, 0.87-0.92). In contrast, a
substantial risk reduction was observed among individuals who engaged in PA at
twice (hazard ratio for 1000 MET-min/wk, 0.81; 95% confidence interval, 0.77
0.86) and 4 times (hazard ratio for 2000 MET-min/wk, 0.65; 95% confidence
interval, 0.58-0.73) the minimum guideline-recommended levels. CONCLUSIONS: There
is an inverse dose-response relationship between PA and HF risk. Doses of PA in
excess of the guideline-recommended minimum PA levels may be required for more
substantial reductions in HF risk.
PMID- 26438782
TI - Physical Activity in the Prevention of Heart Failure: Another Step Forward.
PMID- 26438783
TI - Crizotinib Synergizes with Chemotherapy in Preclinical Models of Neuroblastoma.
AB - PURPOSE: The presence of an ALK aberration correlates with inferior survival for
patients with high-risk neuroblastoma. The emergence of ALK inhibitors such as
crizotinib has provided novel treatment opportunities. However, certain ALK
mutations result in de novo crizotinib resistance, and a phase I trial of
crizotinib showed a lack of response in patients harboring those ALK mutations.
Thus, understanding mechanisms of resistance and defining circumvention
strategies for the clinic is critical. EXPERIMENTAL DESIGN: The sensitivity of
human neuroblastoma-derived cell lines, cell line-derived, and patient-derived
xenograft (PDX) models with varying ALK statuses to crizotinib combined with
topotecan and cyclophosphamide (topo/cyclo) was examined. Cultured cells and
xenografts were evaluated for effects of these drugs on proliferation, signaling,
and cell death, and assessment of synergy. RESULTS: In neuroblastoma murine
xenografts harboring the most common ALK mutations, including those mutations
associated with resistance to crizotinib (but not in those with wild-type ALK),
crizotinib combined with topo/cyclo enhanced tumor responses and mouse event-free
survival. Crizotinib + topo/cyclo showed synergistic cytotoxicity and higher
caspase-dependent apoptosis than crizotinib or topo/cyclo alone in neuroblastoma
cell lines with ALK aberrations (mutation or amplification). CONCLUSIONS:
Combining crizotinib with chemotherapeutic agents commonly used in treating newly
diagnosed patients with high-risk neuroblastoma restores sensitivity in
preclinical models harboring both sensitive ALK aberrations and de novo-resistant
ALK mutations. These data support clinical testing of crizotinib and conventional
chemotherapy with the goal of integrating ALK inhibition into multiagent therapy
for ALK-aberrant neuroblastoma patients.
PMID- 26438784
TI - Handheld echocardiographic screening for rheumatic heart disease by non-experts.
AB - OBJECTIVES: Handheld echocardiography (HAND) has good sensitivity and specificity
for rheumatic heart disease (RHD) when performed by cardiologists. However,
physician shortages in RHD-endemic areas demand less-skilled users to make RHD
screening practical. We examine nurse performance and interpretation of HAND
using a simplified approach for RHD screening. METHODS: Two nurses received
training on HAND and a simplified screening approach. Consented students at two
schools in Uganda were eligible for participation. A simplified approach (HAND
performed and interpreted by a non-expert) was compared with the reference
standard (standard portable echocardiography, performed and interpreted by
experts according to the 2012 World Heart Federation guidelines). Reasons for
false-positive and false-negative HAND studies were identified. RESULTS: A total
of 1002 children were consented, with 956 (11.1 years, 41.8% male) having
complete data for review. Diagnoses included: 913 (95.5%) children were
classified normal, 32 (3.3%) borderline RHD and 11 (1.2%) definite RHD. The
simplified approach had a sensitivity of 74.4% (58.8% to 86.5%) and a specificity
of 78.8% (76.0% to 81.4%) for any RHD (borderline and definite). Sensitivity
improved to 90.9% (58.7% to 98.5%) for definite RHD. Identification and
measurement of erroneous colour jets was the most common reason for false
positive studies (n=164/194), while missed mitral regurgitation and shorter
regurgitant jet lengths with HAND were the most common reasons for false-negative
studies (n=10/11). CONCLUSIONS: Non-expert-led HAND screening programmes offer a
potential solution to financial and workforce barriers that limit widespread RHD
screening. Nurses trained on HAND using a simplified approach had reasonable
sensitivity and specificity for RHD screening. Information on reasons for false
negative and false-positive screening studies should be used to inform future
training protocols, which could lead to improved screening performance.
PMID- 26438785
TI - Adding point of care ultrasound to assess volume status in heart failure patients
in a nurse-led outpatient clinic. A randomised study.
AB - OBJECTIVES: Medical history, physical examination and laboratory testing are not
optimal for the assessment of volume status in heart failure (HF) patients. We
aimed to study the clinical influence of focused ultrasound of the pleural
cavities and inferior vena cava (IVC) performed by specialised nurses to assess
volume status in HF patients at an outpatient clinic. METHODS: HF outpatients
were prospectively included and underwent laboratory testing, history recording
and clinical examination by two nurses with and without an ultrasound examination
of the pleural cavities and IVC using a pocket-size imaging device, in random
order. Each nurse worked in a team with a cardiologist. The influence of the
different diagnostic tests on diuretic dosing was assessed descriptively and in
linear regression analyses. RESULTS: Sixty-two patients were included and 119
examinations were performed. Mean+/-SD age was 74+/-12 years, EF was 34+/-14%,
and N-terminal pro-brain natriuretic peptide (NT-proBNP) value was 3761+/-3072
ng/L. Dosing of diuretics differed between the teams in 31 out of 119
consultations. Weight change and volume status assessed clinically with and
without ultrasound predicted dose adjustment of diuretics at follow-up (p<0.05).
Change of oedema, NT-proBNP, creatinine, and symptoms did not (p>=0.10). In
adjusted analyses, only volume status based on ultrasound predicted dose
adjustments of diuretics at first visit and follow-up (all ultrasound p<=0.01,
all other p>=0.2). CONCLUSIONS: Ultrasound examinations of the pleural cavities
and IVC by nurses may improve diagnostics and patient care in HF patients at an
outpatient clinic, but more studies are needed to determine whether these
examinations have an impact on clinical outcomes. TRIAL REGISTRATION NUMBER:
NCT01794715.
PMID- 26438786
TI - A Conserved Core of Programmed Cell Death Indicator Genes Discriminates
Developmentally and Environmentally Induced Programmed Cell Death in Plants.
AB - A plethora of diverse programmed cell death (PCD) processes has been described in
living organisms. In animals and plants, different forms of PCD play crucial
roles in development, immunity, and responses to the environment. While the
molecular control of some animal PCD forms such as apoptosis is known in great
detail, we still know comparatively little about the regulation of the diverse
types of plant PCD. In part, this deficiency in molecular understanding is caused
by the lack of reliable reporters to detect PCD processes. Here, we addressed
this issue by using a combination of bioinformatics approaches to identify
commonly regulated genes during diverse plant PCD processes in Arabidopsis
(Arabidopsis thaliana). Our results indicate that the transcriptional signatures
of developmentally controlled cell death are largely distinct from the ones
associated with environmentally induced cell death. Moreover, different cases of
developmental PCD share a set of cell death-associated genes. Most of these genes
are evolutionary conserved within the green plant lineage, arguing for an
evolutionary conserved core machinery of developmental PCD. Based on this
information, we established an array of specific promoter-reporter lines for
developmental PCD in Arabidopsis. These PCD indicators represent a powerful
resource that can be used in addition to established morphological and
biochemical methods to detect and analyze PCD processes in vivo and in planta.
PMID- 26438787
TI - The Interplay between Sulfur and Iron Nutrition in Tomato.
AB - Plant response mechanisms to deficiency of a single nutrient, such as sulfur (S)
or iron (Fe), have been described at agronomic, physiological, biochemical,
metabolomics, and transcriptomic levels. However, agroecosystems are often
characterized by different scenarios, in which combined nutrient deficiencies are
likely to occur. Soils are becoming depleted for S, whereas Fe, although highly
abundant in the soil, is poorly available for uptake because of its insolubility
in the soil matrix. To this end, earlier reports showed that a limited S
availability reduces Fe uptake and that Fe deficiency results in the modulation
of sulfate uptake and assimilation. However, the mechanistic basis of this
interaction remains largely unknown. Metabolite profiling of tomato (Solanum
lycopersicum) shoots and roots from plants exposed to Fe, S, and combined Fe and
S deficiency was performed to improve the understanding of the S-Fe interaction
through the identification of the main players in the considered pathways.
Distinct changes were revealed under the different nutritional conditions.
Furthermore, we investigated the development of the Fe deficiency response
through the analysis of expression of ferric chelate reductase, iron-regulated
transporter, and putative transcription factor genes and plant sulfate uptake and
mobilization capacity by analyzing the expression of genes encoding sulfate
transporters (STs) of groups 1, 2, and 4 (SlST1.1, SlST1.2, SlST2.1, SlST2.2, and
SlST4.1). We identified a high degree of common and even synergistic response
patterns as well as nutrient-specific responses. The results are discussed in the
context of current models of nutrient deficiency responses in crop plants.
PMID- 26438788
TI - Comparative Transcriptomics Unravel Biochemical Specialization of Leaf Tissues of
Stevia for Diterpenoid Production.
AB - Stevia (Stevia rebaudiana) produces not only a group of diterpenoid glycosides
known as steviol glycosides (SGs), but also other labdane-type diterpenoids that
may be spatially separated from SGs. However, their biosynthetic routes and
spatial distribution in leaf tissues have not yet been elucidated. Here, we
integrate metabolome and transcriptome analyses of Stevia to explore the
biosynthetic capacity of leaf tissues for diterpenoid metabolism. Tissue-specific
chemical analyses confirmed that SGs were accumulated in leaf cells but not in
trichomes. On the other hand, Stevia leaf trichomes stored other labdane-type
diterpenoids such as oxomanoyl oxide and agatholic acid. RNA sequencing analyses
from two different tissues of Stevia provided a comprehensive overview of dynamic
metabolic activities in trichomes and leaf without trichomes. These metabolite
guided transcriptomics and phylogenetic and gene expression analyses clearly
identified specific gene members encoding enzymes involved in the 2-C-methyl-d
erythritol 4-phosphate pathway and the biosynthesis of steviol or other labdane
type diterpenoids. Additionally, our RNA sequencing analysis uncovered copalyl
diphosphate synthase (SrCPS) and kaurene synthase1 (SrKS1) homologs, SrCPS2 and
KS-like (SrKSL), which were specifically expressed in trichomes. In vitro and in
planta assays showed that unlike SrCPS and SrKS1, SrCPS2 synthesized labda-13-en
8-ol diphosphate and successively catalyzed the formation of manoyl oxide and epi
manoyl oxide in combination with SrKSL. Our findings suggest that Stevia may have
evolved to use distinct metabolic pathways to avoid metabolic interferences in
leaf tissues for efficient production of diverse secondary metabolites.
PMID- 26438789
TI - Phosphorylation of the Light-Harvesting Complex II Isoform Lhcb2 Is Central to
State Transitions.
AB - Light-harvesting complex II (LHCII) is a crucial component of the photosynthetic
machinery, with central roles in light capture and acclimation to changing light.
The association of an LHCII trimer with PSI in the PSI-LHCII supercomplex is
strictly dependent on LHCII phosphorylation mediated by the kinase STATE
TRANSITION7, and is directly related to the light acclimation process called
state transitions. In Arabidopsis (Arabidopsis thaliana), the LHCII trimers
contain isoforms that belong to three classes: Lhcb1, Lhcb2, and Lhcb3. Only
Lhcb1 and Lhcb2 can be phosphorylated in the N-terminal region. Here, we present
an improved Phos-tag-based method to determine the absolute extent of
phosphorylation of Lhcb1 and Lhcb2. Both classes show very similar
phosphorylation kinetics during state transition. Nevertheless, only Lhcb2 is
extensively phosphorylated (>98%) in PSI-LHCII, whereas phosphorylated Lhcb1 is
largely excluded from this supercomplex. Both isoforms are phosphorylated to
different extents in other photosystem supercomplexes and in different domains of
the thylakoid membranes. The data imply that, despite their high sequence
similarity, differential phosphorylation of Lhcb1 and Lhcb2 plays contrasting
roles in light acclimation of photosynthesis.
PMID- 26438790
TI - Long-term survival of Borrelia burgdorferi lacking the hibernation promotion
factor homolog in the unfed tick vector.
AB - Borrelia burgdorferi, a causative agent of Lyme borreliosis, is a zoonotic
pathogen that survives in nutrient-limited environments within a tick, prior to
transmission to its mammalian host. Survival under these prolonged nutrient
limited conditions is thought to be similar to survival during stationary phase,
which is characterized by growth cessation and decreased protein production.
Multiple ribosome-associated proteins are implicated in stationary-phase survival
of Escherichia coli. These proteins include hibernation-promoting factor (HPF),
which dimerizes ribosomes and prevents translation of mRNA. Bioinformatic
analyses indicate that B. burgdorferi harbors an hpf homolog, the bb0449 gene.
BB0449 protein secondary structure modeling also predicted HPF-like structure and
function. However, BB0449 protein was not localized in the ribosome-associated
protein fraction of in vitro-grown B. burgdorferi. In wild-type B. burgdorferi,
bb0449 transcript and BB0449 protein levels are low during various growth phases.
These results are inconsistent with patterns of synthesis of HPF-like proteins in
other bacterial species. In addition, two independently derived bb0449 mutants
successfully completed the mouse-tick infectious cycle, indicating that bb0449 is
not required for prolonged survival in the nutrient-limited environment in the
unfed tick or any other stage of infection by B. burgdorferi. We suggest either
that BB0449 is associated with ribosomes under specific conditions not yet
identified or that BB0449 of B. burgdorferi has a function other than ribosome
conformation modulation.
PMID- 26438791
TI - Global metabolomic analysis of a mammalian host infected with Bacillus anthracis.
AB - Whereas DNA provides the information to design life and proteins provide the
materials to construct it, the metabolome can be viewed as the physiology that
powers it. As such, metabolomics, the field charged with the study of the dynamic
small-molecule fluctuations that occur in response to changing biology, is now
being used to study the basis of disease. Here, we describe a comprehensive
metabolomic analysis of a systemic bacterial infection using Bacillus anthracis,
the etiological agent of anthrax disease, as the model pathogen. An organ and
blood analysis identified approximately 400 metabolites, including several key
classes of lipids involved in inflammation, as being suppressed by B. anthracis.
Metabolite changes were detected as early as 1 day postinfection, well before the
onset of disease or the spread of bacteria to organs, which testifies to the
sensitivity of this methodology. Functional studies using pharmacologic
inhibition of host phospholipases support the idea of a role of these key enzymes
and lipid mediators in host survival during anthrax disease. Finally, the results
are integrated to provide a comprehensive picture of how B. anthracis alters host
physiology. Collectively, the results of this study provide a blueprint for using
metabolomics as a platform to identify and study novel host-pathogen interactions
that shape the outcome of an infection.
PMID- 26438792
TI - Role of B cells in host defense against primary Coxiella burnetii infection.
AB - Despite Coxiella burnetii being an obligate intracellular bacterial pathogen, our
recent study demonstrated that B cells play a critical role in vaccine-induced
immunity to C. burnetii infection by producing protective antibodies. However,
the role of B cells in host defense against primary C. burnetii infection remains
unclear. In this study, we investigated whether B cells play an important role in
host defense against primary C. burnetii infection. The results showed that
peritoneal B cells were able to phagocytose virulent C. burnetii bacteria and
form Coxiella-containing vacuoles (CCVs) and that C. burnetii can infect and
replicate in peritoneal B1a subset B cells in vitro, demonstrating a potential
role for peritoneal B cells in host defense against C. burnetii infection in
vivo. In addition, the results showing that B1a cells secreted a high level of
interleukin-10 (IL-10) in response to C. burnetii infection in vitro suggest that
B1a cells may play an important role in inhibiting the C. burnetii infection
induced inflammatory response. The observation that adoptive transfer of
peritoneal B cells did not significantly affect the severity of C. burnetii
infection-induced diseases in both severe combined immunity-deficient (SCID) and
MUMT mice indicates that peritoneal B cells alone may not be able to control C.
burnetii infection. In contrast, our finding that C. burnetii infection induced
more-severe splenomegaly and a higher bacterial burden in the spleens of B1a cell
deficient Bruton's tyrosine kinase x-linked immunity-deficient (BTK(xid)) mice
than in their wild-type counterparts further suggests that B1a cells play an
important role in host defense against primary C. burnetii infection.
PMID- 26438794
TI - Impact of the Pla protease substrate alpha2-antiplasmin on the progression of
primary pneumonic plague.
AB - Many pathogens usurp the host hemostatic system during infection to promote
pathogenesis. Yersinia pestis, the causative agent of plague, expresses the
plasminogen activator protease Pla, which has been shown in vitro to target and
cleave multiple proteins within the fibrinolytic pathway, including the plasmin
inhibitor alpha2-antiplasmin (A2AP). It is not known, however, if Pla inactivates
A2AP in vivo; the role of A2AP during respiratory Y. pestis infection is not
known either. Here, we show that Y. pestis does not appreciably cleave A2AP in a
Pla-dependent manner in the lungs during experimental pneumonic plague.
Furthermore, following intranasal infection with Y. pestis, A2AP-deficient mice
exhibit no difference in survival time, bacterial burden in the lungs, or
dissemination from wild-type mice. Instead, we found that in the absence of Pla,
A2AP contributes to the control of the pulmonary inflammatory response during
infection by reducing neutrophil recruitment and cytokine production, resulting
in altered immunopathology of the lungs compared to A2AP-deficient mice. Thus,
our data demonstrate that A2AP is not significantly affected by the Pla protease
during pneumonic plague, and although A2AP participates in immune modulation in
the lungs, it has limited impact on the course or ultimate outcome of the
infection.
PMID- 26438793
TI - Outer surface protein OspC is an antiphagocytic factor that protects Borrelia
burgdorferi from phagocytosis by macrophages.
AB - Outer surface protein C (OspC) is one of the major lipoproteins expressed on the
surface of Borrelia burgdorferi during tick feeding and the early phase of
mammalian infection. OspC is required for B. burgdorferi to establish infection
in both immunocompetent and SCID mice and has been proposed to facilitate evasion
of innate immune defenses. However, the exact biological function of OspC remains
elusive. In this study, we showed that the ospC-deficient spirochete could not
establish infection in NOD-scid IL2rgamma(null) mice that lack B cells, T cells,
NK cells, and lytic complement. The ospC mutant also could not establish
infection in anti-Ly6G-treated SCID and C3H/HeN mice (depletion of neutrophils).
However, depletion of mononuclear phagocytes at the skin site of inoculation in
SCID and C3H/HeN mice allowed the ospC mutant to establish infection in vivo. In
phagocyte-depleted mice, the ospC mutant was able to colonize the joints and
triggered neutrophilia during dissemination. Furthermore, we found that
phagocytosis of green fluorescent protein (GFP)-expressing ospC mutant
spirochetes by murine peritoneal macrophages and human THP-1 macrophage-like
cells, but not in PMN-HL60, was significantly higher than parental wild-type B.
burgdorferi strains, suggesting that OspC has an antiphagocytic property. In
addition, overproduction of OspC in spirochetes also decreased the uptake of
spirochetes by murine peritoneal macrophages. Together, our findings provide
evidence that mononuclear phagocytes play a key role in clearance of the ospC
mutant and that OspC promotes spirochetes' evasion of macrophages during early
Lyme borreliosis.
PMID- 26438795
TI - Helicobacter pylori adaptation in vivo in response to a high-salt diet.
AB - Helicobacter pylori exhibits a high level of intraspecies genetic diversity. In
this study, we investigated whether the diversification of H. pylori is
influenced by the composition of the diet. Specifically, we investigated the
effect of a high-salt diet (a known risk factor for gastric adenocarcinoma) on H.
pylori diversification within a host. We analyzed H. pylori strains isolated from
Mongolian gerbils fed either a high-salt diet or a regular diet for 4 months by
proteomic and whole-genome sequencing methods. Compared to the input strain and
output strains from animals fed a regular diet, the output strains from animals
fed a high-salt diet produced higher levels of proteins involved in iron
acquisition and oxidative-stress resistance. Several of these changes were
attributable to a nonsynonymous mutation in fur (fur-R88H). Further experiments
indicated that this mutation conferred increased resistance to high-salt
conditions and oxidative stress. We propose a model in which a high-salt diet
leads to high levels of gastric inflammation and associated oxidative stress in
H. pylori-infected animals and that these conditions, along with the high
intraluminal concentrations of sodium chloride, lead to selection of H. pylori
strains that are most fit for growth in this environment.
PMID- 26438796
TI - Brucella canis is an intracellular pathogen that induces a lower proinflammatory
response than smooth zoonotic counterparts.
AB - Canine brucellosis caused by Brucella canis is a disease of dogs and a zoonotic
risk. B. canis harbors most of the virulence determinants defined for the genus,
but its pathogenic strategy remains unclear since it has not been demonstrated
that this natural rough bacterium is an intracellular pathogen. Studies of B.
canis outbreaks in kennel facilities indicated that infected dogs displaying
clinical signs did not present hematological alterations. A virulent B. canis
strain isolated from those outbreaks readily replicated in different organs of
mice for a protracted period. However, the levels of tumor necrosis factor alpha,
interleukin-6 (IL-6), and IL-12 in serum were close to background levels.
Furthermore, B. canis induced lower levels of gamma interferon, less inflammation
of the spleen, and a reduced number of granulomas in the liver in mice than did
B. abortus. When the interaction of B. canis with cells was studied ex vivo, two
patterns were observed, a predominant scattered cell-associated pattern of
nonviable bacteria and an infrequent intracellular replicative pattern of viable
bacteria in a perinuclear location. The second pattern, responsible for the
increase in intracellular multiplication, was dependent on the type IV secretion
system VirB and was seen only if the inoculum used for cell infections was in
early exponential phase. Intracellular replicative B. canis followed an
intracellular trafficking route undistinguishable from that of B. abortus.
Although B. canis induces a lower proinflammatory response and has a stealthier
replication cycle, it still displays the pathogenic properties of the genus and
the ability to persist in infected organs based on the ability to multiply
intracellularly.
PMID- 26438797
TI - Pathophysiological changes induced by Pseudomonas aeruginosa infection are
involved in MMP-12 and MMP-13 upregulation in human carcinoma epithelial cells
and a pneumonia mouse model.
AB - Pseudomonas aeruginosa infections persist in patients with cystic fibrosis (CF)
and drive lung disease progression. P. aeruginosa potently activates the innate
immune system mostly through the recognition of pathogen-associated molecular
patterns, such as flagellin. Matrix metalloproteinases 12 and 13 (MMP-12 and MMP
13, respectively) exacerbate chronic lung infection and inflammation by promoting
uncontrolled tissue rearrangements and fibrosis, yet the underlying molecular
mechanisms by which this occurs remain largely unknown. In this study, we used
quantitative bacteriology, histological examination, and proinflammatory cytokine
levels to evaluate the effects of MMP-12 and MMP-13 on P. aeruginosa strain K
induced infection and pneumonia in H292 epithelial cells and mice, respectively.
Under inflammatory stimulation, mRNA and protein expression levels of
proinflammatory mediators were higher in strain K-infected mice and cells than in
uninfected counterparts, in which MMP-12 and MMP-13 expression reached levels
similar to those observed in epithelial cells. Moreover, we also found that the
NF-kappaB pathway might be involved in the induction of cytokines in response to
strain K infection. Taken together, these data suggest that MMP-12 and MMP-13
alter strain K infection in mice and play a role in inflammatory regulation by
modulating cytokine levels.
PMID- 26438798
TI - Pancreatic amylase is an environmental signal for regulation of biofilm formation
and host interaction in Campylobacter jejuni.
AB - Campylobacter jejuni is a commensal bacterium in the intestines of animals and
birds and a major cause of food-borne gastroenteritis in humans worldwide. Here
we show that exposure to pancreatic amylase leads to secretion of an alpha
dextran by C. jejuni and that a secreted protease, Cj0511, is required. Exposure
of C. jejuni to pancreatic amylase promotes biofilm formation in vitro, increases
interaction with human epithelial cell lines, increases virulence in the Galleria
mellonella infection model, and promotes colonization of the chicken ileum. We
also show that exposure to pancreatic amylase protects C. jejuni from stress
conditions in vitro, suggesting that the induced alpha-dextran may be important
during transmission between hosts. This is the first evidence that pancreatic
amylase functions as an interkingdom signal in an enteric microorganism.
PMID- 26438801
TI - "Power and Greed and the Corruptible Seed": Mental Disability, Prosecutorial
Misconduct, and the Death Penalty.
PMID- 26438800
TI - Gut Microbiota and Brain Function: An Evolving Field in Neuroscience.
AB - There is a growing appreciation of the importance of gut microbiota to health and
disease. This has been driven by advances in sequencing technology and recent
findings demonstrating the important role of microbiota in common health
disorders such as obesity. Moreover, the potential role of gut microbiota in
influencing brain function, behavior, and mental health has attracted the
attention of neuroscientists and psychiatrists. At the 29(th) International
College of Neuropsychopharmacology (CINP) World Congress held in Vancouver,
Canada, in June 2014, a group of experts presented the symposium, "Gut microbiota
and brain function: Relevance to psychiatric disorders" to review the latest
findings in how gut microbiota may play a role in brain function, behavior, and
disease. The symposium covered a broad range of topics, including gut microbiota
and neuroendocrine function, the influence of gut microbiota on behavior,
probiotics as regulators of brain and behavior, and imaging the gut-brain axis in
humans. This report provides an overview of these presentations.
PMID- 26438799
TI - Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors.
AB - BACKGROUND: Leptin, an adipose-derived hormone, has been implicated in emotional
regulation. We have previously shown that systemic administration of leptin
produces anxiolytic-like effects and deletion of the leptin receptor, LepRb, in
midbrain dopamine neurons leads to an anxiogenic phenotype. This study
investigated whether activation or deletion of LepRb in the ventral tegmental
area of adult mice is capable of inducing anxiolytic and anxiogenic effects,
respectively. METHODS: Mice were cannulated in the ventral tegmental area and
received bilateral intra-ventral tegmental area infusions of leptin or the
JAK2/STAT3 inhibitor AG490. Anxiety-like behaviors were assessed using the
elevated plus-maze, light-dark box, and novelty suppressed feeding tests.
Deletion of LepRb in the ventral tegmental area was achieved by bilateral
injection of AAV-Cre into the ventral tegmental area of adult Lepr(flox/flox)
mice. Anxiety-related behaviors were evaluated 3 weeks after viral injection.
RESULTS: Intra-ventral tegmental area infusions of leptin reduced anxiety-like
behaviors, as indicated by increased percent open-arm time and open-arm entries
in the elevated plus-maze test, increased time spent in the light side and
decreased latency to enter the light side of the light-dark box, and decreased
latency to feed in the novelty suppressed feeding test. Blockade of JAK2/STAT3
signaling in the ventral tegmental area by AG490 attenuated the anxiolytic effect
produced by systemic administration of leptin. Lepr(flox/flox) mice injected with
AAV-Cre into the ventral tegmental area showed decreased leptin-induced STAT3
phosphorylation and enhanced anxiety-like behaviors in the elevated plus-maze
test and the novelty suppressed feeding test. CONCLUSIONS: These findings suggest
that leptin-LepRb signaling in the ventral tegmental area plays an important role
in the regulation of anxiety-related behaviors.
PMID- 26438802
TI - Realistic Consideration of Women and Violence is Critical.
PMID- 26438803
TI - Mental Health and Immigrant Detainees in the United States: Competency and Self
Representation.
AB - Most immigrant detainees held in U.S. Immigration and Customs Enforcement (ICE)
facilities do not have legal representation, because immigration proceedings are
a matter of civil, not criminal, law. In 2005, Mr. Franco, an immigrant from
Mexico with an IQ between 35 and 55, was found incompetent to stand trial, but
was not appointed an attorney for his immigration proceedings. This failure led
to a class action lawsuit, known as the Franco litigation, and in April 2013, a
federal judge ordered the U. S. government to provide legal representation for
immigrant detainees in California, Arizona, and Washington who are incompetent to
represent themselves due to a mental disorder or defect. This development has
implications for forensic evaluators, because there is likely to be an increase
in the number of competency examinations requested by courts for immigrant
detainees. Furthermore, forensic evaluators must understand that an evaluation
for competency of an immigrant detainee includes both the Dusky criteria and
capacity for self-representation. In this article, we explore the legal context
and ethics concerns related to the Franco litigation.
PMID- 26438804
TI - Commentary: Mental Health and Immigrant Detainees in the United States.
AB - In this commentary, we reflect on Korngold and colleagues' comprehensive review
of the legal challenges encountered by mentally ill immigrant detainees in the
United States. Specifically, we further review the competency question as it
relates to detainees, as well as recent developments in the legal system. We
expand the discussion to general treatment and care of mentally ill detainees in
United States Immigration and Customs Enforcement (ICE) facilities. In addition,
we provide an allegory to the juvenile justice system and discuss cultural
considerations. We conclude by highlighting the significant implications changes
in the immigration justice system may have for forensic examiners and competency
evaluations.
PMID- 26438805
TI - Cognitive Fluctuations and the Lucid Interval in Dementia: Implications for
Testamentary Capacity.
AB - The lucid interval is a long-held legal concept widely accepted in case law as a
possible means of countering a challenge to testamentary and related capacities.
In parallel, the clinical phenomenon of cognitive fluctuations has been
considered a common element of several neurodegenerative disorders (dementias),
including Alzheimer Disease, but is especially prevalent in vascular dementia and
dementia with Lewy bodies. In this article, we review the objective evidence for
cognitive fluctuations in dementia and the implications for the validity of the
legal notion of the lucid interval cited in recent case law. The literature on
cognitive fluctuations in dementia shows that such fluctuations largely affect
attention and alertness, rather than memory or the higher level executive
functions that are essential components of testamentary capacity. Moreover, these
fluctuations are small in magnitude and very short in duration. These findings
cast doubt on the validity of the lucid interval and invite a critical rethinking
of this legal concept as applied to will challenges involving testators with
dementia.
PMID- 26438806
TI - Commentary: Contested Wills and Will Contests.
AB - When disinherited heirs challenge a will drafted by a person suspected of having
dementia, a legal battle may ensue. The "lucid interval," a brief return to
competence from a state of dementia, has been invoked in years past to establish
the validity of contested wills. Shulman et al., having reviewed the medical and
legal literature, make a convincing argument that no such period of competence
occurs in the course of dementia. A neuropsychiatric autopsy is outlined in this
commentary to provide a method of determining the validity of a last will and
testament, by applying the clinical method described when witness statements do
not provide accurate guidance.
PMID- 26438807
TI - Commentary: The Lucid Interval-Coping with Unscientific Terminology.
AB - The authors agree with Shulman et al. in their assertion that the term "lucid
interval" does not describe what is now known to occur in the fluctuating mental
status of some demented individuals. Therefore, its use by the courts to
determine competency in such persons can result in an unjust outcome. However, we
believe such criticism as Shulman and his coauthors levied at the legal
profession should be broadened to consider antiquated and nonscientific
terminology in our own field of psychiatry.
PMID- 26438808
TI - Male Perpetrators of Intimate Partner Homicide: A Review and Proposed Typology.
AB - Nearly one in seven homicides worldwide involve killing of an intimate partner,
and men are four times more likely to be the perpetrators of these offenses. This
article is a review of the literature on male perpetrators of intimate partner
homicide (IPH) with an emphasis on the demographic, psychiatric, situational, and
motivational characteristics consistently identified across diverse posthomicide
samples. The existing literature supports the heterogeneity among male
perpetrators of IPH. Based on patterns that emerge in the literature, a
preliminary typology is described that includes four generally distinct subtypes
of male IPH perpetrators: the mentally ill, the undercontrolled/dysregulated,
chronic batterer, and overcontrolled/catathymic subtypes. Forensic implications
related to risk assessment, risk management, and criminal intent are considered,
and suggestions for future targeted research aimed at validating the proposed
typology are offered.
PMID- 26438809
TI - Nature and Utilization of Civil Commitment for Substance Abuse in the United
States.
AB - Substance abuse is a leading cause of morbidity and mortality in the United
States. Although civil commitment has been used to address substance abuse for
more than a century, little is known today about the nature and use of substance
related commitment laws in the United States. We examined statutes between July
2010 and October 2012 from all 50 states and the District of Columbia for
provisions authorizing civil commitment of adults for substance abuse and
recorded the criteria and evidentiary standard for commitment and the location
and the maximum duration of commitment orders. High-level state representatives
evaluated these data and provided information on the use of commitment. Thirty
three states have statutory provisions for the civil commitment of persons
because of substance abuse. The application of these statutes ranged from a few
commitment cases to thousands annually. Although dangerousness was the most
common basis for commitment, many states permitted it in other contexts. The
maximum duration of treatment ranged from less than 1 month to more than 1 year
for both initial and subsequent civil commitment orders. These findings show wide
variability in the nature and application of civil commitment statutes for
substance abuse in the United States. Such diversity reflects a lack of consensus
on the role that civil commitment should play in managing substance abuse and the
problems associated with it.
PMID- 26438810
TI - The Defense of Involuntary Intoxication by Prescribed Medications: An Appellate
Case Review.
AB - The defense of involuntary intoxication has long been an exception to the general
notion that intoxication is not a defense to criminal liability. The consumption
of medications prescribed by a physician can form the basis of an involuntary
intoxication defense. In this article, I review cases where defendants relied on
the use of prescribed medications for an involuntary-intoxication defense. The
medications most frequently implicated by defendants are listed by name and by
class. From the case law, I provide a summary of the defense and a review of the
pitfalls of the defense to serve as practice pointers for forensic evaluators.
PMID- 26438811
TI - Correlates of Competency to Stand Trial Among Youths Admitted to a Juvenile
Mental Health Court.
AB - Competency to stand trial (CST) assessment of juvenile offenders is a relatively
recent phenomenon, as are juvenile mental health courts. Factors associated with
youths' ability to participate in legal proceedings are not well understood,
regardless of the court venue. Using a sample of 324 juveniles participating in
the Los Angeles County Juvenile Mental Health Court (LAJMHC), we sought to
explore the relationships of age, mental health diagnosis, and history of mental
health treatment to CST status. Results suggest youths under the age of 15 were
significantly more likely to have been found incompetent to stand trial (IST)
when compared with older youths (p = .007). Youths with a diagnosis of a
pervasive developmental disorder or intellectual disability were also more likely
to be found IST than those without these diagnoses (p = .02 and p = .0001,
respectively). Conversely, participants aged 16 or 17 years and diagnosed with a
mood, substance abuse, or psychotic disorder were more likely to be found CST
than those without these diagnoses (p < .0001, p = .035, and p = .0064,
respectively). Participants with a history of psychotherapy or psychotropic
medication were more likely to be found CST than were those without any treatment
history (p < .0001). Further research on factors that affect CST status in
juveniles who participate in mental health courts may be particularly salient to
improve understanding of specific treatment and rehabilitative needs of youthful
offenders, and to inform approaches to competency attainment and recidivism
prevention services, both within these specialty courts and in juvenile
proceedings in general.
PMID- 26438812
TI - Treatment of Mentally Ill Offenders in Nine Developing Latin American Countries.
AB - The prevalence of psychiatric conditions among prisoners in Latin America is
greatly underestimated, and because of the lack of awareness about mental illness
among service providers in Latin American prisons, oftentimes these conditions go
unrecognized or are not treated properly. In the worst-case scenarios, human
rights violations occur. Despite the high levels of need, many prisoners have not
received adequate or timely treatment. The sparse existing literature documents
prison conditions throughout Latin American countries, ranging from poor to
extremely harsh, overcrowded, and life threatening. Most prison systems do not
meet international prison standards. The information on forensic mental health
services and the treatment of offenders with mental illness have been less
extensively studied and compared with forensic practices in developed American
nations. This study analyzes the existing literature on forensic psychiatry,
focusing on nine socioeconomically developing nations in Latin America, to
improve understanding of treatment approaches for offenders with mental illness
and identify emerging themes. A review was conducted and data were included in
regression analyses to investigate information relative to the treatment of
offenders with mental illness and its interaction with the mental health system.
PMID- 26438813
TI - Implications of the 2014 Senate Select Committee on Intelligence Report for
Forensic Mental Health in the War on Terror.
AB - In December 2014, the Senate Select Committee on Intelligence released a
declassified executive summary on the use by the Central Intelligence Agency
(CIA) of enhanced interrogation techniques against suspected terrorist detainees
in the War on Terror. The report relies on 6 million pages of documents that
describe the CIA's Detention and Interrogation Program, providing a systematic
and comprehensive investigation into covert military and intelligence practices
after the attacks on September 11, 2001. This article presents an analysis of key
findings related to forensic mental health. I explore their implications for the
ethics of mental health professionals who work with military and intelligence
agencies and for facts disputed within the Guantanamo military commission system.
Opportunities for further study and theoretical development are outlined.
PMID- 26438814
TI - Pregnant Women and the Use of Corrections Restraints and Substance Use
Commitment.
AB - Recent evolving trends in the United States legal system regarding how policies
and laws are applied to pregnant women include concerns over the use of
restraints or shackles in pregnant inmates and forced treatment or commitment of
pregnant women for substance abuse. These topics raise many questions, such as:
how violent are women, particularly pregnant women; what are the informed consent
and treatment implications; and who is at risk of harm? In addition, questions
have been raised regarding maternal versus fetal rights, especially when the
mother uses substances during a pregnancy. We review legal decisions and
organizational position statements and highlight ethics-related concerns.
PMID- 26438815
TI - Expanding Slayer Statutes to Elder Abuse.
AB - Common law has a dictum that people must not benefit from their crimes. In years
past, states have enacted slayer rules to prevent killers from inheriting from
their victims. The specific criteria and applicability of slayer rules vary by
jurisdiction. Recently, several states, including Washington, have expanded their
slayer rules to disqualify persons from inheriting if they have been involved in
abuse or financial exploitation of the deceased. Reviewed herein are the abuse
disinheritance laws, the relationship of the laws to concepts of testamentary
capacity and undue influence, and the relevance to forensic psychiatric
evaluations.
PMID- 26438816
TI - A lambda Cro-Like Repressor Is Essential for the Induction of Conjugative
Transfer of SXT/R391 Elements in Response to DNA Damage.
AB - Integrative and conjugative elements (ICEs) of the SXT/R391 family are the main
contributors to acquired multidrug resistance in the seventh pandemic lineage of
Vibrio cholerae, the etiological agent of the diarrheal disease cholera.
Conjugative transfer of SXT/R391 ICEs is triggered by antibiotics and agents
promoting DNA damage through RecA-dependent autoproteolysis of SetR, an ICE
encoded lambda CI-like repressor. Here, we describe the role of CroS, a distant
lambda Cro homolog, as a key component contributing to the regulation of
expression of the activator SetCD that orchestrates the expression of the
conjugative transfer genes. We show that deletion of croS abolishes the SOS
response-dependent induction of SXT despite the presence of a functional setR
gene. Using quantitative reverse transcription-PCR and lacZ reporter assays, we
also show that CroS represses setR and setCD expression by binding to operator
sites shared with SetR. Furthermore, we provide evidence of an additional
operator site bound by SetR and CroS. Finally, we show that SetCD expression
generates a positive feedback loop due to SXT excision and replication in a
fraction of the cell population. Together, these results refine our understanding
of the genetic regulation governing the propagation of major vectors of multidrug
resistance. IMPORTANCE: Healthcare systems worldwide are challenged by an
alarming drug resistance crisis caused by the massive and rapid propagation of
antibiotic resistance genes and the associated emergence of multidrug-resistant
pathogenic bacteria. SXT/R391 ICEs contribute to this phenomenon not only in
clinical and environmental vibrios but also in several members of the family
Enterobacteriaceae. We have identified and characterized here the regulator CroS
as a key factor in the stimulation of conjugative transfer of these ICEs in
response to DNA-damaging agents. We have also untangled conflicting evidence
regarding autoactivation of transfer by the master activator of SXT/R391 ICEs,
SetCD. Discovery of CroS provides a clearer and more complete understanding of
the regulatory network that governs the dissemination of SXT/R391 ICEs in
bacterial populations.
PMID- 26438817
TI - Airpnp: Auto- and Integrated Regulation of Polynucleotide Phosphorylase.
AB - The properties and expression of polynucleotide phosphorylase (PNPase), capable
of both RNA degradation and polymerization, have been studied for 60 years. In
this issue of the Journal of Bacteriology, Park et al. (H. Park, H. Yakhnin, M.
Connolly, T. Romeo, and P. Babitzke, J Bacteriol 197:3751-3759, 2015,
http://dx.doi.org/10.1128/JB.00721-15) write the latest chapter on the complex
regulation of pnp gene expression involving CsrA. I describe how this new piece
of the puzzle fits into the global scheme of PNPase autoregulation and how this
is influenced by central carbon metabolism at both the posttranscriptional level
and that of enzyme activity.
PMID- 26438818
TI - CsrA Participates in a PNPase Autoregulatory Mechanism by Selectively Repressing
Translation of pnp Transcripts That Have Been Previously Processed by RNase III
and PNPase.
AB - Csr is a conserved global regulatory system that represses or activates gene
expression posttranscriptionally. CsrA of Escherichia coli is a homodimeric RNA
binding protein that regulates transcription elongation, translation initiation,
and mRNA stability by binding to the 5' untranslated leader or initial coding
sequence of target transcripts. pnp mRNA, encoding the 3' to 5' exoribonuclease
polynucleotide phosphorylase (PNPase), was previously identified as a CsrA target
by transcriptome sequencing (RNA-seq). Previous studies also showed that RNase
III and PNPase participate in a pnp autoregulatory mechanism in which RNase III
cleavage of the untranslated leader, followed by PNPase degradation of the
resulting 5' fragment, leads to pnp repression by an undefined translational
repression mechanism. Here we demonstrate that CsrA binds to two sites in pnp
leader RNA but only after the transcript is fully processed by RNase III and
PNPase. In the absence of processing, both of the binding sites are sequestered
in an RNA secondary structure, which prevents CsrA binding. The CsrA dimer
bridges the upstream high-affinity site to the downstream site that overlaps the
pnp Shine-Dalgarno sequence such that bound CsrA causes strong repression of pnp
translation. CsrA-mediated translational repression also leads to a small
increase in the pnp mRNA decay rate. Although CsrA has been shown to regulate
translation and mRNA stability of numerous genes in a variety of organisms, this
is the first example in which prior mRNA processing is required for CsrA-mediated
regulation. IMPORTANCE: CsrA protein represses translation of numerous mRNA
targets, typically by binding to multiple sites in the untranslated leader region
preceding the coding sequence. We found that CsrA represses translation of pnp by
binding to two sites in the pnp leader transcript but only after it is processed
by RNase III and PNPase. Processing by these two ribonucleases alters the mRNA
secondary structure such that it becomes accessible to the ribosome for
translation as well as to CsrA. As one of the CsrA binding sites overlaps the pnp
ribosome binding site, bound CsrA prevents ribosome binding. This is the first
example in which regulation by CsrA requires prior mRNA processing and should
link pnp expression to conditions affecting CsrA activity.
PMID- 26438819
TI - p21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to
Initiate Feedback Inhibition of Rac1 GTPase.
AB - Phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 2 (PREX2)
is a guanine nucleotide exchange factor (GEF) for the Ras-related C3 botulinum
toxin substrate 1 (Rac1) GTPase, facilitating the exchange of GDP for GTP on
Rac1. GTP-bound Rac1 then activates its downstream effectors, including p21
activated kinases (PAKs). PREX2 and Rac1 are frequently mutated in cancer and
have key roles within the insulin-signaling pathway. Rac1 can be inactivated by
multiple mechanisms; however, negative regulation by insulin is not well
understood. Here, we show that in response to being activated after insulin
stimulation, Rac1 initiates its own inactivation by decreasing PREX2 GEF
activity. Following PREX2-mediated activation of Rac1 by the second messengers
PIP3 or Gbetagamma, we found that PREX2 was phosphorylated through a PAK
dependent mechanism. PAK-mediated phosphorylation of PREX2 reduced GEF activity
toward Rac1 by inhibiting PREX2 binding to PIP3 and Gbetagamma. Cell
fractionation experiments also revealed that phosphorylation prevented PREX2 from
localizing to the cellular membrane. Furthermore, the onset of insulin-induced
phosphorylation of PREX2 was delayed compared with AKT. Altogether, we propose
that second messengers activate the Rac1 signal, which sets in motion a cascade
whereby PAKs phosphorylate and negatively regulate PREX2 to decrease Rac1
activation. This type of regulation would allow for transient activation of the
PREX2-Rac1 signal and may be relevant in multiple physiological processes,
including diseases such as diabetes and cancer when insulin signaling is
chronically activated.
PMID- 26438820
TI - Structural Insights into the High-efficiency Catalytic Mechanism of the Sterile
alpha-Motif/Histidine-Aspartate Domain-containing Protein.
AB - Sterile alpha-motif/histidine-aspartate domain-containing protein (SAMHD1), a
homo-tetrameric GTP/dGTP-dependent dNTP triphosphohydrolase, catalyzes the
conversion of dNTP into deoxynucleoside and triphosphate. As the only
characterized dNTP triphosphohydrolase in human cells, SAMHD1 plays an important
role in human innate immunity, autoimmunity, and cell cycle control. Previous
biochemical studies and crystal structures have revealed that SAMHD1
interconverts between an inactive monomeric or dimeric form and a dGTP/GTP
induced active tetrameric form. Here, we describe a novel state of SAMHD1 (109
626 amino acids, SAMHD1C) that is characterized by a rapid initial hydrolysis
rate. Interestingly, the crystal structure showed that this novel SAMHD1 tetramer
contains only GTP and has structural features distinct from the GTP/dNTP-bound
SAMHD1 tetramer. Our work thus reveals structural features of SAMHD1 that may
represent one of its biological assembly states in cells. The biochemical and
structural information generated by the present study not only provides an
ordered pathway for the assembly and activation of SAMHD1 but also provides
insights into the potential mechanisms of the high-efficiency catalytic activity
of this enzyme family in vivo.
PMID- 26438821
TI - Macrophage-specific de Novo Synthesis of Ceramide Is Dispensable for Inflammasome
driven Inflammation and Insulin Resistance in Obesity.
AB - Dietary lipid overload and calorie excess during obesity is a low grade chronic
inflammatory state with diminished ability to appropriately metabolize glucose or
lipids. Macrophages are critical in maintaining adipose tissue homeostasis, in
part by regulating lipid metabolism, energy homeostasis, and tissue remodeling.
During high fat diet-induced obesity, macrophages are activated by lipid derived
"danger signals" such as ceramides and palmitate and promote the adipose tissue
inflammation in an Nlrp3 inflammasome-dependent manner. Given that the metabolic
fate of fatty acids in macrophages is not entirely elucidated, we have
hypothesized that de novo synthesis of ceramide, through the rate-limiting enzyme
serine palmitoyltransferase long chain (Sptlc)-2, is required for saturated fatty
acid-driven Nlrp3 inflammasome activation in macrophages. Here we report that
mitochondrial targeted overexpression of catalase, which is established to
mitigate oxidative stress, controls ceramide-induced Nlrp3 inflammasome
activation but does not affect the ATP-mediated caspase-1 cleavage. Surprisingly,
myeloid cell-specific deletion of Sptlc2 is not required for palmitate-driven
Nlrp3 inflammasome activation. Furthermore, the ablation of Sptlc2 in macrophages
did not impact macrophage polarization or obesity-induced adipose tissue
leukocytosis. Consistent with these data, investigation of insulin resistance
using hyperinsulinemic-euglycemic clamps revealed no significant differences in
obese mice lacking ceramide de novo synthesis machinery in macrophages. These
data suggest that alternate metabolic pathways control fatty acid-derived
ceramide synthesis in macrophage and the Nlrp3 inflammasome activation in
obesity.
PMID- 26438822
TI - An Integrated Approach for Analysis of the DNA Damage Response in Mammalian
Cells: NUCLEOTIDE EXCISION REPAIR, DNA DAMAGE CHECKPOINT, AND APOPTOSIS.
AB - DNA damage by UV and UV-mimetic agents elicits a set of inter-related responses
in mammalian cells, including DNA repair, DNA damage checkpoints, and apoptosis.
Conventionally, these responses are analyzed separately using different
methodologies. Here we describe a unified approach that is capable of quantifying
all three responses in parallel using lysates from the same population of cells.
We show that a highly sensitive in vivo excision repair assay is capable of
detecting nucleotide excision repair of a wide spectrum of DNA lesions (UV
damage, chemical carcinogens, and chemotherapeutic drugs) within minutes of
damage induction. This method therefore allows for a real-time measure of
nucleotide excision repair activity that can be monitored in conjunction with
other components of the DNA damage response, including DNA damage checkpoint and
apoptotic signaling. This approach therefore provides a convenient and reliable
platform for simultaneously examining multiple aspects of the DNA damage response
in a single population of cells that can be applied for a diverse array of
carcinogenic and chemotherapeutic agents.
PMID- 26438823
TI - Proton Matrix ENDOR Studies on Ca2+-depleted and Sr2+-substituted Manganese
Cluster in Photosystem II.
AB - Proton matrix ENDOR spectra were measured for Ca(2+)-depleted and Sr(2+)
substituted photosystem II (PSII) membrane samples from spinach and core
complexes from Thermosynechococcus vulcanus in the S2 state. The ENDOR spectra
obtained were similar for untreated PSII from T. vulcanus and spinach, as well as
for Ca(2+)-containing and Sr(2+)-substituted PSII, indicating that the proton
arrangements around the manganese cluster in cyanobacterial and higher plant PSII
and Ca(2+)-containing and Sr(2+)-substituted PSII are similar in the S2 state, in
agreement with the similarity of the crystal structure of both Ca(2+)-containing
and Sr(2+)-substituted PSII in the S1 state. Nevertheless, slightly different
hyperfine separations were found between Ca(2+)-containing and Sr(2+)-substituted
PSII because of modifications of the water protons ligating to the Sr(2+) ion.
Importantly, Ca(2+) depletion caused the loss of ENDOR signals with a 1.36-MHz
separation because of the loss of the water proton W4 connecting Ca(2+) and YZ
directly. With respect to the crystal structure and the functions of Ca(2+) in
oxygen evolution, it was concluded that the roles of Ca(2+) and Sr(2+) involve
the maintenance of the hydrogen bond network near the Ca(2+) site and electron
transfer pathway to the manganese cluster.
PMID- 26438824
TI - Multipart Chaperone-Effector Recognition in the Type III Secretion System of
Chlamydia trachomatis.
AB - Secretion of effector proteins into the eukaryotic host cell is required for
Chlamydia trachomatis virulence. In the infection process, Scc1 and Scc4, two
chaperones of the type III secretion (T3S) system, facilitate secretion of the
important effector and plug protein, CopN, but little is known about the details
of this event. Here we use biochemistry, mass spectrometry, nuclear magnetic
resonance spectroscopy, and genetic analyses to characterize this trimolecular
event. We find that Scc4 complexes with Scc1 and CopN in situ at the late
developmental cycle of C. trachomatis. We show that Scc4 and Scc1 undergo dynamic
interactions as part of the unique bacterial developmental cycle. Using alanine
substitutions, we identify several amino acid residues in Scc4 that are critical
for the Scc4-Scc1 interaction, which is required for forming the Scc4.Scc1.CopN
ternary complex. These results, combined with our previous findings that Scc4
plays a role in transcription (Rao, X., Deighan, P., Hua, Z., Hu, X., Wang, J.,
Luo, M., Wang, J., Liang, Y., Zhong, G., Hochschild, A., and Shen, L. (2009)
Genes Dev. 23, 1818-1829), reveal that the T3S process is linked to bacterial
transcriptional events, all of which are mediated by Scc4 and its interacting
proteins. A model describing how the T3S process may affect gene expression is
proposed.
PMID- 26438825
TI - Two-pore Channels (TPC2s) and Nicotinic Acid Adenine Dinucleotide Phosphate
(NAADP) at Lysosomal-Sarcoplasmic Reticular Junctions Contribute to Acute and
Chronic beta-Adrenoceptor Signaling in the Heart.
AB - Ca(2+)-permeable type 2 two-pore channels (TPC2) are lysosomal proteins required
for nicotinic acid adenine dinucleotide phosphate (NAADP)-evoked Ca(2+) release
in many diverse cell types. Here, we investigate the importance of TPC2 proteins
for the physiology and pathophysiology of the heart. NAADP-AM failed to enhance
Ca(2+) responses in cardiac myocytes from Tpcn2(-/-) mice, unlike myocytes from
wild-type (WT) mice. Ca(2+)/calmodulin-dependent protein kinase II inhibitors
suppressed actions of NAADP in myocytes. Ca(2+) transients and contractions
accompanying action potentials were increased by isoproterenol in myocytes from
WT mice, but these effects of beta-adrenoreceptor stimulation were reduced in
myocytes from Tpcn2(-/-) mice. Increases in amplitude of L-type Ca(2+) currents
evoked by isoproterenol remained unchanged in myocytes from Tpcn2(-/-) mice
showing no loss of beta-adrenoceptors or coupling mechanisms. Whole hearts from
Tpcn2(-/-) mice also showed reduced inotropic effects of isoproterenol and a
reduced tendency for arrhythmias following acute beta-adrenoreceptor stimulation.
Hearts from Tpcn2(-/-) mice chronically exposed to isoproterenol showed less
cardiac hypertrophy and increased threshold for arrhythmogenesis compared with WT
controls. Electron microscopy showed that lysosomes form close contacts with the
sarcoplasmic reticulum (separation ~ 25 nm). We propose that Ca(2+)-signaling
nanodomains between lysosomes and sarcoplasmic reticulum dependent on NAADP and
TPC2 comprise an important element in beta-adrenoreceptor signal transduction in
cardiac myocytes. In summary, our observations define a role for NAADP and TPC2
at lysosomal/sarcoplasmic reticulum junctions as unexpected but major
contributors in the acute actions of beta-adrenergic signaling in the heart and
also in stress pathways linking chronic stimulation of beta-adrenoceptors to
hypertrophy and associated arrhythmias.
PMID- 26438826
TI - High Glucose-induced Retinal Pericyte Apoptosis Depends on Association of GAPDH
and Siah1.
AB - Diabetic retinopathy (DR) is a leading cause of blindness worldwide, and its
prevalence is growing. Current therapies for DR address only the later stages of
the disease, are invasive, and have limited effectiveness. Retinal pericyte death
is an early pathologic feature of DR. Although it has been observed in diabetic
patients and in animal models of DR, the cause of pericyte death remains unknown.
A novel pro-apoptotic pathway initiated by the interaction between glyceraldehyde
3-phosphate dehydrogenase (GAPDH) and the E3 ubiquitin ligase, seven in absentia
homolog 1 (Siah1), was recently identified in ocular tissues. In this article we
examined the involvement of the GAPDH/Siah1 interaction in human retinal pericyte
(hRP) apoptosis. HRP were cultured in 5 mm normal glucose, 25 mm l- or d-glucose
for 48 h (osmotic control and high glucose treatments, respectively). Siah1 siRNA
was used to down-regulate Siah1 expression. TAT-FLAG GAPDH and/or Siah1-directed
peptides were used to block GAPDH and Siah1 interaction. Co-immunoprecipitation
assays were conducted to analyze the effect of high glucose on the association of
GAPDH and Siah1. Apoptosis was measured by Annexin V staining and caspase-3
enzymatic activity assay. High glucose increased Siah1 total protein levels,
induced the association between GAPDH and Siah1, and led to GAPDH nuclear
translocation. Our findings demonstrate that dissociation of the GAPDH/Siah1 pro
apoptotic complex can block high glucose-induced pericyte apoptosis, widely
considered a hallmark feature of DR. Thus, the work presented in this article can
provide a foundation to identify novel targets for early treatment of DR.
PMID- 26438827
TI - Prion aggregate structure in yeast cells is determined by the Hsp104-Hsp110
disaggregase machinery.
AB - Prions consist of misfolded proteins that have adopted an infectious amyloid
conformation. In vivo, prion biogenesis is intimately associated with the protein
quality control machinery. Using electron tomography, we probed the effects of
the heat shock protein Hsp70 chaperone system on the structure of a model yeast
[PSI+] prion in situ. Individual Hsp70 deletions shift the balance between fibril
assembly and disassembly, resulting in a variable shell of nonfibrillar, but
still immobile, aggregates at the surface of the [PSI+] prion deposits. Both
Hsp104 (an Hsp100 disaggregase) and Sse1 (the major yeast form of Hsp110) were
localized to this surface shell of [PSI+] deposits in the deletion mutants.
Elevation of Hsp104 expression promoted the appearance of this novel,
nonfibrillar form of the prion aggregate. Moreover, Sse1 was found to regulate
prion fibril length. Our studies reveal a key role for Sse1 (Hsp110), in
cooperation with Hsp104, in regulating the length and assembly state of [PSI+]
prion fibrils in vivo.
PMID- 26438828
TI - SAM68 is a physiological regulator of SMN2 splicing in spinal muscular atrophy.
AB - Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by loss of
motor neurons in patients with null mutations in the SMN1 gene. The almost
identical SMN2 gene is unable to compensate for this deficiency because of the
skipping of exon 7 during pre-messenger RNA (mRNA) processing. Although several
splicing factors can modulate SMN2 splicing in vitro, the physiological
regulators of this disease-causing event are unknown. We found that knockout of
the splicing factor SAM68 partially rescued body weight and viability of
SMADelta7 mice. Ablation of SAM68 function promoted SMN2 splicing and expression
in SMADelta7 mice, correlating with amelioration of SMA-related defects in motor
neurons and skeletal muscles. Mechanistically, SAM68 binds to SMN2 pre-mRNA,
favoring recruitment of the splicing repressor hnRNP A1 and interfering with that
of U2AF65 at the 3' splice site of exon 7. These findings identify SAM68 as the
first physiological regulator of SMN2 splicing in an SMA mouse model.
PMID- 26438829
TI - RanGTP aids anaphase entry through Ubr5-mediated protein turnover.
AB - RanGTP is known to regulate the spindle assembly checkpoint (SAC), but the
underlying molecular mechanism is unclear. BuGZ stabilizes SAC protein Bub3
through direct interaction and facilitates its mitotic function. Here we show
that RanGTP promotes the turnover of BuGZ and Bub3 in metaphase, which in turn
facilitates metaphase-to-anaphase transition. BuGZ and Bub3 interact with either
importin-beta or an E3 ubiquitin ligase, Ubr5. RanGTP promotes the dissociation
of importin-beta from BuGZ and Bub3 in metaphase. This results in increased
binding of BuGZ and Bub3 to Ubr5, leading to ubiquitination and subsequent
turnover of both proteins. We propose that elevated metaphase RanGTP levels use
Ubr5 to couple overall chromosome congression to SAC silencing.
PMID- 26438830
TI - Growth factor signaling to mTORC1 by amino acid-laden macropinosomes.
AB - The rapid activation of the mechanistic target of rapamycin complex-1 (mTORC1) by
growth factors is increased by extracellular amino acids through yet-undefined
mechanisms of amino acid transfer into endolysosomes. Because the endocytic
process of macropinocytosis concentrates extracellular solutes into endolysosomes
and is increased in cells stimulated by growth factors or tumor-promoting phorbol
esters, we analyzed its role in amino acid-dependent activation of mTORC1. Here,
we show that growth factor-dependent activation of mTORC1 by amino acids, but not
glucose, requires macropinocytosis. In murine bone marrow-derived macrophages and
murine embryonic fibroblasts stimulated with their cognate growth factors or with
phorbol myristate acetate, activation of mTORC1 required an Akt-independent
vesicular pathway of amino acid delivery into endolysosomes, mediated by the
actin cytoskeleton. Macropinocytosis delivered small, fluorescent fluid-phase
solutes into endolysosomes sufficiently fast to explain growth factor-mediated
signaling by amino acids. Therefore, the amino acid-laden macropinosome is an
essential and discrete unit of growth factor receptor signaling to mTORC1.
PMID- 26438831
TI - Resistance to ketolide antibiotics by coordinated expression of rRNA
methyltransferases in a bacterial producer of natural ketolides.
AB - Ketolides are promising new antimicrobials effective against a broad range of
Gram-positive pathogens, in part because of the low propensity of these drugs to
trigger the expression of resistance genes. A natural ketolide pikromycin and a
related compound methymycin are produced by Streptomyces venezuelae strain ATCC
15439. The producer avoids the inhibitory effects of its own antibiotics by
expressing two paralogous rRNA methylase genes pikR1 and pikR2 with seemingly
redundant functions. We show here that the PikR1 and PikR2 enzymes mono- and
dimethylate, respectively, the N6 amino group in 23S rRNA nucleotide A2058. PikR1
monomethylase is constitutively expressed; it confers low resistance at low
fitness cost and is required for ketolide-induced activation of pikR2 to attain
high-level resistance. The regulatory mechanism controlling pikR2 expression has
been evolutionary optimized for preferential activation by ketolide antibiotics.
The resistance genes and the induction mechanism remain fully functional when
transferred to heterologous bacterial hosts. The anticipated wide use of ketolide
antibiotics could promote horizontal transfer of these highly efficient
resistance genes to pathogens. Taken together, these findings emphasized the need
for surveillance of pikR1/pikR2-based bacterial resistance and the preemptive
development of drugs that can remain effective against the ketolide-specific
resistance mechanism.
PMID- 26438832
TI - Discovery of progenitor cell signatures by time-series synexpression analysis
during Drosophila embryonic cell immortalization.
AB - The use of time series profiling to identify groups of functionally related genes
(synexpression groups) is a powerful approach for the discovery of gene function.
Here we apply this strategy during Ras(V12) immortalization of Drosophila
embryonic cells, a phenomenon not well characterized. Using high-resolution
transcriptional time-series datasets, we generated a gene network based on
temporal expression profile similarities. This analysis revealed that common
immortalized cells are related to adult muscle precursors (AMPs), a stem cell
like population contributing to adult muscles and sharing properties with
vertebrate satellite cells. Remarkably, the immortalized cells retained the
capacity for myogenic differentiation when treated with the steroid hormone
ecdysone. Further, we validated in vivo the transcription factor CG9650, the
ortholog of mammalian Bcl11a/b, as a regulator of AMP proliferation predicted by
our analysis. Our study demonstrates the power of time series synexpression
analysis to characterize Drosophila embryonic progenitor lines and identify
stem/progenitor cell regulators.
PMID- 26438833
TI - pH homeostasis during coral calcification in a free ocean CO2 enrichment (FOCE)
experiment, Heron Island reef flat, Great Barrier Reef.
AB - Geochemical analyses (delta(11)B and Sr/Ca) are reported for the coral Porites
cylindrica grown within a free ocean carbon enrichment (FOCE) experiment,
conducted on the Heron Island reef flat (Great Barrier Reef) for a 6-mo period
from June to early December 2010. The FOCE experiment was designed to simulate
the effects of CO2-driven acidification predicted to occur by the end of this
century (scenario RCP4.5) while simultaneously maintaining the exposure of corals
to natural variations in their environment under in situ conditions. Analyses of
skeletal growth (measured from extension rates and skeletal density) showed no
systematic differences between low-pH FOCE treatments (DeltapH = ~-0.05 to -0.25
units below ambient) and present day controls (DeltapH = 0) for calcification
rates or the pH of the calcifying fluid (pHcf); the latter was derived from boron
isotopic compositions (delta(11)B) of the coral skeleton. Furthermore, individual
nubbins exhibited near constant delta(11)B compositions along their primary
apical growth axes (+/-0.02 pHcf units) regardless of the season or treatment.
Thus, under the highly dynamic conditions of the Heron Island reef flat, P.
cylindrica up-regulated the pH of its calcifying fluid (pHcf ~8.4-8.6), with each
nubbin having near-constant pHcf values independent of the large natural seasonal
fluctuations of the reef flat waters (pH ~7.7 to ~8.3) or the superimposed FOCE
treatments. This newly discovered phenomenon of pH homeostasis during
calcification indicates that coral living in highly dynamic environments exert
strong physiological controls on the carbonate chemistry of their calcifying
fluid, implying a high degree of resilience to ocean acidification within the
investigated ranges.
PMID- 26438834
TI - Medieval warming initiated exceptionally large wildfire outbreaks in the Rocky
Mountains.
AB - Many of the largest wildfires in US history burned in recent decades, and climate
change explains much of the increase in area burned. The frequency of extreme
wildfire weather will increase with continued warming, but many uncertainties
still exist about future fire regimes, including how the risk of large fires will
persist as vegetation changes. Past fire-climate relationships provide an
opportunity to constrain the related uncertainties, and reveal widespread burning
across large regions of western North America during past warm intervals. Whether
such episodes also burned large portions of individual landscapes has been
difficult to determine, however, because uncertainties with the ages of past
fires and limited spatial resolution often prohibit specific estimates of past
area burned. Accounting for these challenges in a subalpine landscape in
Colorado, we estimated century-scale fire synchroneity across 12 lake-sediment
charcoal records spanning the past 2,000 y. The percentage of sites burned only
deviated from the historic range of variability during the Medieval Climate
Anomaly (MCA) between 1,200 and 850 y B.P., when temperatures were similar to
recent decades. Between 1,130 and 1,030 y B.P., 83% (median estimate) of our
sites burned when temperatures increased ~0.5 degrees C relative to the
preceding centuries. Lake-based fire rotation during the MCA decreased to an
estimated 120 y, representing a 260% higher rate of burning than during the
period of dendroecological sampling (360 to -60 y B.P.). Increased burning,
however, did not persist throughout the MCA. Burning declined abruptly before
temperatures cooled, indicating possible fuel limitations to continued burning.
PMID- 26438835
TI - Photon gating in four-dimensional ultrafast electron microscopy.
AB - Ultrafast electron microscopy (UEM) is a pivotal tool for imaging of nanoscale
structural dynamics with subparticle resolution on the time scale of atomic
motion. Photon-induced near-field electron microscopy (PINEM), a key UEM
technique, involves the detection of electrons that have gained energy from a
femtosecond optical pulse via photon-electron coupling on nanostructures. PINEM
has been applied in various fields of study, from materials science to biological
imaging, exploiting the unique spatial, energy, and temporal characteristics of
the PINEM electrons gained by interaction with a "single" light pulse. The
further potential of photon-gated PINEM electrons in probing ultrafast dynamics
of matter and the optical gating of electrons by invoking a "second" optical
pulse has previously been proposed and examined theoretically in our group. Here,
we experimentally demonstrate this photon-gating technique, and, through
diffraction, visualize the phase transition dynamics in vanadium dioxide
nanoparticles. With optical gating of PINEM electrons, imaging temporal
resolution was improved by a factor of 3 or better, being limited only by the
optical pulse widths. This work enables the combination of the high spatial
resolution of electron microscopy and the ultrafast temporal response of the
optical pulses, which provides a promising approach to attain the resolution of
few femtoseconds and attoseconds in UEM.
PMID- 26438836
TI - Mutation of the ER retention receptor KDELR1 leads to cell-intrinsic lymphopenia
and a failure to control chronic viral infection.
AB - Endoplasmic reticulum (ER)-resident proteins are continually retrieved from the
Golgi and returned to the ER by Lys-Asp-Glu-Leu (KDEL) receptors, which bind to
an eponymous tetrapeptide motif at their substrate's C terminus. Mice and humans
possess three paralogous KDEL receptors, but little is known about their
functional redundancy, or if their mutation can be physiologically tolerated.
Here, we present a recessive mouse missense allele of the prototypical mammalian
KDEL receptor, KDEL ER protein retention receptor 1 (KDELR1). Kdelr1 homozygous
mutants were mildly lymphopenic, as were mice with a CRISPR/Cas9-engineered
frameshift allele. Lymphopenia was cell intrinsic and, in the case of T cells,
was associated with reduced expression of the T-cell receptor (TCR) and increased
expression of CD44, and could be partially corrected by an MHC class I-restricted
TCR transgene. Antiviral immunity was also compromised, with Kdelr1 mutant mice
unable to clear an otherwise self-limiting viral infection. These data reveal a
nonredundant cellular function for KDELR1, upon which lymphocytes distinctly
depend.
PMID- 26438837
TI - Indoleamine 2,3-dioxygenase-1 is protective in atherosclerosis and its
metabolites provide new opportunities for drug development.
AB - Atherosclerosis is the major cause of cardiovascular disease (CVD), the leading
cause of death worldwide. Despite much focus on lipid abnormalities in
atherosclerosis, it is clear that the immune system also has important pro- and
antiatherogenic functions. The enzyme indoleamine-2,3-dioxygenase (IDO) catalyses
degradation of the essential amino acid tryptophan into immunomodulatory
metabolites. How IDO deficiency affects immune responses during atherogenesis is
unknown and we explored potential mechanisms in models of murine and human
atherosclerosis. IDO deficiency in hypercholesterolemic ApoE(-/-) mice caused a
significant increase in lesion size and surrogate markers of plaque
vulnerability. No significant changes in cholesterol levels were observed but
decreases in IL-10 production were found in the peripheral blood, spleen and
lymph node B cells of IDO-deficient compared with IDO-competent ApoE(-/-) mice.
3,4,-Dimethoxycinnamoyl anthranilic acid (3,4-DAA), an orally active synthetic
derivative of the tryptophan metabolite anthranilic acid, but not l-kynurenine,
enhanced production of IL-10 in cultured splenic B cells. Finally, 3,4-DAA
treatment reduced lesion formation and inflammation after collar-induced arterial
injury in ApoE(-/-) mice, and reduced cytokine and chemokine production in ex
vivo human atheroma cell cultures. Our data demonstrate that endogenous
production of tryptophan metabolites via IDO is an essential feedback loop that
controls atherogenesis and athero-inflammation. We show that the IDO pathway
induces production of IL-10 in B cells in vivo and in vitro, suggesting that IDO
may induce immunoregulatory functions of B cells in atherosclerosis. The
favorable effects of anthranilic acid derivatives in atherosclerosis indicate a
novel approach toward therapy of CVD.
PMID- 26438838
TI - Epithelial estrogen receptor 1 intrinsically mediates squamous differentiation in
the mouse vagina.
AB - Estrogen-mediated actions in female reproductive organs are tightly regulated,
mainly through estrogen receptor 1 (ESR1). The mouse vaginal epithelium
cyclically exhibits cell proliferation and differentiation in response to
estrogen and provides a unique model for analyzing the homeostasis of stratified
squamous epithelia. To address the role of ESR1-mediated tissue events during
homeostasis, we analyzed mice with a vaginal epithelium-specific knockout of Esr1
driven by keratin 5-Cre (K5-Esr1KO). We show here that loss of epithelial ESR1 in
the vagina resulted in aberrant epithelial cell proliferation in the suprabasal
cell layers and led to failure of keratinized differentiation. Gene expression
analysis showed that several known estrogen target genes, including erbB growth
factor ligands, were not induced by estrogen in the K5-Esr1KO mouse vagina. Organ
culture experiments revealed that the addition of erbB growth factor ligands,
such as amphiregulin, could activate keratinized differentiation in the absence
of epithelial ESR1. Thus, epithelial ESR1 integrates estrogen and growth factor
signaling to mediate regulation of cell proliferation in squamous
differentiation, and our results provide new insights into estrogen-mediated
homeostasis in female reproductive organs.
PMID- 26438839
TI - Coexistence of both gyroid chiralities in individual butterfly wing scales of
Callophrys rubi.
AB - The wing scales of the Green Hairstreak butterfly Callophrys rubi consist of
crystalline domains with sizes of a few micrometers, which exhibit a congenitally
handed porous chitin microstructure identified as the chiral triply periodic
single-gyroid structure. Here, the chirality and crystallographic texture of
these domains are investigated by means of electron tomography. The tomograms
unambiguously reveal the coexistence of the two enantiomeric forms of opposite
handedness: the left- and right-handed gyroids. These two enantiomers appear with
nonequal probabilities, implying that molecularly chiral constituents of the
biological formation process presumably invoke a chiral symmetry break, resulting
in a preferred enantiomeric form of the gyroid structure. Assuming validity of
the formation model proposed by Ghiradella H (1989) J Morphol 202(1):69-88 and
Saranathan V, et al. (2010) Proc Natl Acad Sci USA 107(26):11676-11681, where the
two enantiomeric labyrinthine domains of the gyroid are connected to the
extracellular and intra-SER spaces, our findings imply that the structural
chirality of the single gyroid is, however, not caused by the molecular chirality
of chitin. Furthermore, the wing scales are found to be highly textured, with a
substantial fraction of domains exhibiting the <001> directions of the gyroid
crystal aligned parallel to the scale surface normal. Both findings are needed to
completely understand the photonic purpose of the single gyroid in gyroid-forming
butterflies. More importantly, they show the level of control that morphogenesis
exerts over secondary features of biological nanostructures, such as chirality or
crystallographic texture, providing inspiration for biomimetic replication
strategies for synthetic self-assembly mechanisms.
PMID- 26438840
TI - Optofluidic wavelength division multiplexing for single-virus detection.
AB - Optical waveguides simultaneously transport light at different colors, forming
the basis of fiber-optic telecommunication networks that shuttle data in dozens
of spectrally separated channels. Here, we reimagine this wavelength division
multiplexing (WDM) paradigm in a novel context--the differentiated detection and
identification of single influenza viruses on a chip. We use a single multimode
interference (MMI) waveguide to create wavelength-dependent spot patterns across
the entire visible spectrum and enable multiplexed single biomolecule detection
on an optofluidic chip. Each target is identified by its time-dependent
fluorescence signal without the need for spectral demultiplexing upon detection.
We demonstrate detection of individual fluorescently labeled virus particles of
three influenza A subtypes in two implementations: labeling of each virus using
three different colors and two-color combinatorial labeling. By extending
combinatorial multiplexing to three or more colors, MMI-based WDM provides the
multiplexing power required for differentiated clinical tests and the growing
field of personalized medicine.
PMID- 26438841
TI - Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual
chromatin organization amenable to epigenetic manipulation.
AB - Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide
and is a major risk factor for liver failure and hepatocellular carcinoma.
Current antiviral therapy inhibits cytoplasmic HBV genomic replication, but is
not curative because it does not directly affect nuclear HBV closed circular DNA
(cccDNA), the genomic form that templates viral transcription and sustains viral
persistence. Novel approaches that directly target cccDNA regulation would
therefore be highly desirable. cccDNA is assembled with cellular histone proteins
into chromatin, but little is known about the regulation of HBV chromatin by
histone posttranslational modifications (PTMs). Here, using a new cccDNA ChIP-Seq
approach, we report, to our knowledge, the first genome-wide maps of PTMs in
cccDNA-containing chromatin from de novo infected HepG2 cells, primary human
hepatocytes, and from HBV-infected liver tissue. We find high levels of PTMs
associated with active transcription enriched at specific sites within the HBV
genome and, surprisingly, very low levels of PTMs linked to transcriptional
repression even at silent HBV promoters. We show that transcription and active
PTMs in HBV chromatin are reduced by the activation of an innate immunity
pathway, and that this effect can be recapitulated with a small molecule
epigenetic modifying agent, opening the possibility that chromatin-based
regulation of cccDNA transcription could be a new therapeutic approach to chronic
HBV infection.
PMID- 26438842
TI - NO binding kinetics in myoglobin investigated by picosecond Fe K-edge absorption
spectroscopy.
AB - Diatomic ligands in hemoproteins and the way they bind to the active center are
central to the protein's function. Using picosecond Fe K-edge X-ray absorption
spectroscopy, we probe the NO-heme recombination kinetics with direct sensitivity
to the Fe-NO binding after 532-nm photoexcitation of nitrosylmyoglobin (MbNO) in
physiological solutions. The transients at 70 and 300 ps are identical, but they
deviate from the difference between the static spectra of deoxymyoglobin and
MbNO, showing the formation of an intermediate species. We propose the latter to
be a six-coordinated domed species that is populated on a timescale of ~ 200 ps
by recombination with NO ligands. This work shows the feasibility of ultrafast
pump-probe X-ray spectroscopic studies of proteins in physiological media,
delivering insight into the electronic and geometric structure of the active
center.
PMID- 26438843
TI - cKit+ cardiac progenitors of neural crest origin.
AB - The degree to which cKit-expressing progenitors generate cardiomyocytes in the
heart is controversial. Genetic fate-mapping studies suggest minimal
contribution; however, whether or not minimal contribution reflects minimal
cardiomyogenic capacity is unclear because the embryonic origin and role in
cardiogenesis of these progenitors remain elusive. Using high-resolution genetic
fate-mapping approaches with cKit(CreERT2/+) and Wnt1::Flpe mouse lines, we show
that cKit delineates cardiac neural crest progenitors (CNC(kit)). CNC(kit)
possess full cardiomyogenic capacity and contribute to all CNC derivatives,
including cardiac conduction system cells. Furthermore, by modeling cardiogenesis
in cKit(CreERT2)-induced pluripotent stem cells, we show that, paradoxically, the
cardiogenic fate of CNC(kit) is regulated by bone morphogenetic protein
antagonism, a signaling pathway activated transiently during establishment of the
cardiac crescent, and extinguished from the heart before CNC invasion. Together,
these findings elucidate the origin of cKit(+) cardiac progenitors and suggest
that a nonpermissive cardiac milieu, rather than minimal cardiomyogenic capacity,
controls the degree of CNC(kit) contribution to myocardium.
PMID- 26438844
TI - Genome-wide modeling of transcription kinetics reveals patterns of RNA production
delays.
AB - Genes with similar transcriptional activation kinetics can display very different
temporal mRNA profiles because of differences in transcription time, degradation
rate, and RNA-processing kinetics. Recent studies have shown that a splicing
associated RNA production delay can be significant. To investigate this issue
more generally, it is useful to develop methods applicable to genome-wide
datasets. We introduce a joint model of transcriptional activation and mRNA
accumulation that can be used for inference of transcription rate, RNA production
delay, and degradation rate given data from high-throughput sequencing time
course experiments. We combine a mechanistic differential equation model with a
nonparametric statistical modeling approach allowing us to capture a broad range
of activation kinetics, and we use Bayesian parameter estimation to quantify the
uncertainty in estimates of the kinetic parameters. We apply the model to data
from estrogen receptor alpha activation in the MCF-7 breast cancer cell line. We
use RNA polymerase II ChIP-Seq time course data to characterize transcriptional
activation and mRNA-Seq time course data to quantify mature transcripts. We find
that 11% of genes with a good signal in the data display a delay of more than 20
min between completing transcription and mature mRNA production. The genes
displaying these long delays are significantly more likely to be short. We also
find a statistical association between high delay and late intron retention in
pre-mRNA data, indicating significant splicing-associated production delays in
many genes.
PMID- 26438845
TI - Psychological and neural correlates of the emergence of morality in toddlers.
PMID- 26438846
TI - Targeting glutamine metabolism rescues mice from late-stage cerebral malaria.
AB - The most deadly complication of Plasmodium falciparum infection is cerebral
malaria (CM) with a case fatality rate of 15-25% in African children despite
effective antimalarial chemotherapy. There are no adjunctive treatments for CM,
so there is an urgent need to identify new targets for therapy. Here we show that
the glutamine analog 6-diazo-5-oxo-L-norleucine (DON) rescues mice from CM when
administered late in the infection a time at which mice already are suffering
blood-brain barrier dysfunction, brain swelling, and hemorrhaging accompanied by
accumulation of parasite-specific CD8(+) effector T cells and infected red blood
cells in the brain. Remarkably, within hours of DON treatment mice showed blood
brain barrier integrity, reduced brain swelling, decreased function of activated
effector CD8(+) T cells in the brain, and levels of brain metabolites that
resembled those in uninfected mice. These results suggest DON as a strong
candidate for an effective adjunctive therapy for CM in African children.
PMID- 26438847
TI - Relation between rainfall intensity and savanna tree abundance explained by water
use strategies.
AB - Tree abundance in tropical savannas exhibits large and unexplained spatial
variability. Here, we propose that differentiated tree and grass water use
strategies can explain the observed negative relation between maximum tree
abundance and rainfall intensity (defined as the characteristic rainfall depth on
rainy days), and we present a biophysical tree-grass competition model to test
this idea. The model is founded on a premise that has been well established in
empirical studies, namely, that the relative growth rate of grasses is much
higher compared with trees in wet conditions but that grasses are more
susceptible to water stress and lose biomass more quickly in dry conditions. The
model is coupled with a stochastic rainfall generator and then calibrated and
tested using field observations from several African savanna sites. We show that
the observed negative relation between maximum tree abundance and rainfall
intensity can be explained only when differentiated water use strategies are
accounted for. Numerical experiments reveal that this effect is more significant
than the effect of root niche separation. Our results emphasize the importance of
vegetation physiology in determining the responses of tree abundance to climate
variations in tropical savannas and suggest that projected increases in rainfall
intensity may lead to an increase in grass in this biome.
PMID- 26438849
TI - Elevation of 20-carbon long chain bases due to a mutation in serine
palmitoyltransferase small subunit b results in neurodegeneration.
AB - Sphingolipids typically have an 18-carbon (C18) sphingoid long chain base (LCB)
backbone. Although sphingolipids with LCBs of other chain lengths have been
identified, the functional significance of these low-abundance sphingolipids is
unknown. The LCB chain length is determined by serine palmitoyltransferase (SPT)
isoenzymes, which are trimeric proteins composed of two large subunits (SPTLC1
and SPTLC2 or SPTLC3) and a small subunit (SPTssa or SPTssb). Here we report the
identification of an Sptssb mutation, Stellar (Stl), which increased the SPT
affinity toward the C18 fatty acyl-CoA substrate by twofold and significantly
elevated 20-carbon (C20) LCB production in the mutant mouse brain and eye,
resulting in surprising neurodegenerative effects including aberrant membrane
structures, accumulation of ubiquitinated proteins on membranes, and axon
degeneration. Our work demonstrates that SPT small subunits play a major role in
controlling SPT activity and substrate affinity, and in specifying sphingolipid
LCB chain length in vivo. Moreover, our studies also suggest that excessive C20
LCBs or C20 LCB-containing sphingolipids impair protein homeostasis and neural
functions.
PMID- 26438848
TI - A respiratory chain controlled signal transduction cascade in the mitochondrial
intermembrane space mediates hydrogen peroxide signaling.
AB - Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) govern cellular
homeostasis by inducing signaling. H2O2 modulates the activity of phosphatases
and many other signaling molecules through oxidation of critical cysteine
residues, which led to the notion that initiation of ROS signaling is broad and
nonspecific, and thus fundamentally distinct from other signaling pathways. Here,
we report that H2O2 signaling bears hallmarks of a regular signal transduction
cascade. It is controlled by hierarchical signaling events resulting in a focused
response as the results place the mitochondrial respiratory chain upstream of
tyrosine-protein kinase Lyn, Lyn upstream of tyrosine-protein kinase SYK (Syk),
and Syk upstream of numerous targets involved in signaling, transcription,
translation, metabolism, and cell cycle regulation. The active mediators of H2O2
signaling colocalize as H2O2 induces mitochondria-associated Lyn and Syk
phosphorylation, and a pool of Lyn and Syk reside in the mitochondrial
intermembrane space. Finally, the same intermediaries control the signaling
response in tissues and species responsive to H2O2 as the respiratory chain, Lyn,
and Syk were similarly required for H2O2 signaling in mouse B cells, fibroblasts,
and chicken DT40 B cells. Consistent with a broad role, the Syk pathway is
coexpressed across tissues, is of early metazoan origin, and displays evidence of
evolutionary constraint in the human. These results suggest that H2O2 signaling
is under control of a signal transduction pathway that links the respiratory
chain to the mitochondrial intermembrane space-localized, ubiquitous, and ancient
Syk pathway in hematopoietic and nonhematopoietic cells.
PMID- 26438850
TI - Dissecting pigment architecture of individual photosynthetic antenna complexes in
solution.
AB - Oligomerization plays a critical role in shaping the light-harvesting properties
of many photosynthetic pigment-protein complexes, but a detailed understanding of
this process at the level of individual pigments is still lacking. To study the
effects of oligomerization, we designed a single-molecule approach to probe the
photophysical properties of individual pigment sites as a function of protein
assembly state. Our method, based on the principles of anti-Brownian
electrokinetic trapping of single fluorescent proteins, step-wise photobleaching,
and multiparameter spectroscopy, allows pigment-specific spectroscopic
information on single multipigment antennae to be recorded in a nonperturbative
aqueous environment with unprecedented detail. We focus on the monomer-to-trimer
transformation of allophycocyanin (APC), an important antenna protein in
cyanobacteria. Our data reveal that the two chemically identical pigments in APC
have different roles. One (alpha) is the functional pigment that red-shifts its
spectral properties upon trimer formation, whereas the other (beta) is a
"protective" pigment that persistently quenches the excited state of alpha in the
prefunctional, monomer state of the protein. These results show how subtleties in
pigment organization give rise to functionally important aspects of energy
transfer and photoprotection in antenna complexes. The method developed here
should find immediate application in understanding the emergent properties of
other natural and artificial light-harvesting systems.
PMID- 26438851
TI - Region-wide synchrony and traveling waves of dengue across eight countries in
Southeast Asia.
AB - Dengue is a mosquito-transmitted virus infection that causes epidemics of febrile
illness and hemorrhagic fever across the tropics and subtropics worldwide. Annual
epidemics are commonly observed, but there is substantial spatiotemporal
heterogeneity in intensity. A better understanding of this heterogeneity in
dengue transmission could lead to improved epidemic prediction and disease
control. Time series decomposition methods enable the isolation and study of
temporal epidemic dynamics with a specific periodicity (e.g., annual cycles
related to climatic drivers and multiannual cycles caused by dynamics in
population immunity). We collected and analyzed up to 18 y of monthly dengue
surveillance reports on a total of 3.5 million reported dengue cases from 273
provinces in eight countries in Southeast Asia, covering ~ 10(7) km(2). We
detected strong patterns of synchronous dengue transmission across the entire
region, most markedly during a period of high incidence in 1997-1998, which was
followed by a period of extremely low incidence in 2001-2002. This synchrony in
dengue incidence coincided with elevated temperatures throughout the region in
1997-1998 and the strongest El Nino episode of the century. Multiannual dengue
cycles (2-5 y) were highly coherent with the Oceanic Nino Index, and synchrony of
these cycles increased with temperature. We also detected localized traveling
waves of multiannual dengue epidemic cycles in Thailand, Laos, and the
Philippines that were dependent on temperature. This study reveals forcing
mechanisms that drive synchronization of dengue epidemics on a continental scale
across Southeast Asia.
PMID- 26438852
TI - Remodeling nuclear architecture allows efficient transport of herpesvirus capsids
by diffusion.
AB - The nuclear chromatin structure confines the movement of large macromolecular
complexes to interchromatin corrals. Herpesvirus capsids of approximately 125 nm
assemble in the nucleoplasm and must reach the nuclear membranes for egress.
Previous studies concluded that nuclear herpesvirus capsid motility is active,
directed, and based on nuclear filamentous actin, suggesting that large nuclear
complexes need metabolic energy to escape nuclear entrapment. However, this
hypothesis has recently been challenged. Commonly used microscopy techniques do
not allow the imaging of rapid nuclear particle motility with sufficient
spatiotemporal resolution. Here, we use a rotating, oblique light sheet, which we
dubbed a ring-sheet, to image and track viral capsids with high temporal and
spatial resolution. We do not find any evidence for directed transport. Instead,
infection with different herpesviruses induced an enlargement of interchromatin
domains and allowed particles to diffuse unrestricted over longer distances,
thereby facilitating nuclear egress for a larger fraction of capsids.
PMID- 26438853
TI - A holistic picture of Austronesian migrations revealed by phylogeography of
Pacific paper mulberry.
AB - The peopling of Remote Oceanic islands by Austronesian speakers is a fascinating
and yet contentious part of human prehistory. Linguistic, archaeological, and
genetic studies have shown the complex nature of the process in which different
components that helped to shape Lapita culture in Near Oceania each have their
own unique history. Important evidence points to Taiwan as an Austronesian
ancestral homeland with a more distant origin in South China, whereas alternative
models favor South China to North Vietnam or a Southeast Asian origin. We test
these propositions by studying phylogeography of paper mulberry, a common East
Asian tree species introduced and clonally propagated since prehistoric times
across the Pacific for making barkcloth, a practical and symbolic component of
Austronesian cultures. Using the hypervariable chloroplast ndhF-rpl32 sequences
of 604 samples collected from East Asia, Southeast Asia, and Oceanic islands
(including 19 historical herbarium specimens from Near and Remote Oceania), 48
haplotypes are detected and haplotype cp-17 is predominant in both Near and
Remote Oceania. Because cp-17 has an unambiguous Taiwanese origin and cp-17
carrying Oceanic paper mulberries are clonally propagated, our data concur with
expectations of Taiwan as the Austronesian homeland, providing circumstantial
support for the "out of Taiwan" hypothesis. Our data also provide insights into
the dispersal of paper mulberry from South China "into North Taiwan," the "out of
South China-Indochina" expansion to New Guinea, and the geographic origins of
post-European introductions of paper mulberry into Oceania.
PMID- 26438854
TI - Contribution of cyanobacterial alkane production to the ocean hydrocarbon cycle.
AB - Hydrocarbons are ubiquitous in the ocean, where alkanes such as pentadecane and
heptadecane can be found even in waters minimally polluted with crude oil.
Populations of hydrocarbon-degrading bacteria, which are responsible for the
turnover of these compounds, are also found throughout marine systems, including
in unpolluted waters. These observations suggest the existence of an unknown and
widespread source of hydrocarbons in the oceans. Here, we report that strains of
the two most abundant marine cyanobacteria, Prochlorococcus and Synechococcus,
produce and accumulate hydrocarbons, predominantly C15 and C17 alkanes, between
0.022 and 0.368% of dry cell weight. Based on global population sizes and
turnover rates, we estimate that these species have the capacity to produce 2-540
pg alkanes per mL per day, which translates into a global ocean yield of ~ 308
771 million tons of hydrocarbons annually. We also demonstrate that both obligate
and facultative marine hydrocarbon-degrading bacteria can consume cyanobacterial
alkanes, which likely prevents these hydrocarbons from accumulating in the
environment. Our findings implicate cyanobacteria and hydrocarbon degraders as
key players in a notable internal hydrocarbon cycle within the upper ocean, where
alkanes are continually produced and subsequently consumed within days.
Furthermore we show that cyanobacterial alkane production is likely sufficient to
sustain populations of hydrocarbon-degrading bacteria, whose abundances can
rapidly expand upon localized release of crude oil from natural seepage and human
activities.
PMID- 26438855
TI - Current extinction rates of reptiles and amphibians.
AB - There is broad concern that a mass extinction of amphibians and reptiles is now
underway. Here I apply an extremely conservative Bayesian method to estimate the
number of recent amphibian and squamate extinctions in nine important tropical
and subtropical regions. The data stem from a combination of museum collection
databases and published site surveys. The method computes an extinction
probability for each species by considering its sighting frequency and last
sighting date. It infers hardly any extinction when collection dates are
randomized and it provides underestimates when artificial extinction events are
imposed. The method also appears to be insensitive to trends in sampling;
therefore, the counts it provides are absolute minimums. Extinctions or severe
population crashes have accumulated steadily since the 1970s and 1980s, and at
least 3.1% of frog species have already disappeared. Based on these data and this
conservative method, the best estimate of the global grand total is roughly 200
extinctions. Consistent with previous results, frog losses are heavy in Latin
America, which has been greatly affected by the pathogenic chytrid fungus
Batrachochytrium dendrobatidis. Extinction rates are now four orders-of-magnitude
higher than background, and at least another 6.9% of all frog species may be lost
within the next century, even if there is no acceleration in the growth of
environmental threats.
PMID- 26438856
TI - Resource colimitation governs plant community responses to altered precipitation.
AB - Ecological theory and evidence suggest that plant community biomass and
composition may often be jointly controlled by climatic water availability and
soil nutrient supply. To the extent that such colimitation operates, alterations
in water availability caused by climatic change may have relatively little effect
on plant communities on nutrient-poor soils. We tested this prediction with a 5-y
rainfall and nutrient manipulation in a semiarid annual grassland system with
highly heterogeneous soil nutrient supplies. On nutrient-poor soils, rainfall
addition alone had little impact, but rainfall and nutrient addition synergized
to cause large increases in biomass, declines in diversity, and near-complete
species turnover. Plant species with resource-conservative functional traits (low
specific leaf area, short stature) were replaced by species with resource
acquisitive functional traits (high specific leaf area, tall stature). On
nutrient-rich soils, in contrast, rainfall addition alone caused substantial
increases in biomass, whereas fertilization had little effect. Our results
highlight that multiple resource limitation is a critical aspect when predicting
the relative vulnerability of natural communities to climatically induced
compositional change and diversity loss.
PMID- 26438857
TI - Allowing variance may enlarge the safe operating space for exploited ecosystems.
AB - Variable flows of food, water, or other ecosystem services complicate planning.
Management strategies that decrease variability and increase predictability may
therefore be preferred. However, actions to decrease variance over short
timescales (2-4 y), when applied continuously, may lead to long-term ecosystem
changes with adverse consequences. We investigated the effects of managing short
term variance in three well-understood models of ecosystem services: lake
eutrophication, harvest of a wild population, and yield of domestic herbivores on
a rangeland. In all cases, actions to decrease variance can increase the risk of
crossing critical ecosystem thresholds, resulting in less desirable ecosystem
states. Managing to decrease short-term variance creates ecosystem fragility by
changing the boundaries of safe operating spaces, suppressing information needed
for adaptive management, cancelling signals of declining resilience, and removing
pressures that may build tolerance of stress. Thus, the management of variance
interacts strongly and inseparably with the management of resilience. By allowing
for variation, learning, and flexibility while observing change, managers can
detect opportunities and problems as they develop while sustaining the capacity
to deal with them.
PMID- 26438858
TI - Kin discrimination between sympatric Bacillus subtilis isolates.
AB - Kin discrimination, broadly defined as differential treatment of conspecifics
according to their relatedness, could help biological systems direct cooperative
behavior toward their relatives. Here we investigated the ability of the soil
bacterium Bacillus subtilis to discriminate kin from nonkin in the context of
swarming, a cooperative multicellular behavior. We tested a collection of
sympatric conspecifics from soil in pairwise combinations and found that despite
their history of coexistence, the vast majority formed distinct boundaries when
the swarms met. Some swarms did merge, and most interestingly, this behavior was
only seen in the most highly related strain pairs. Overall the swarm interaction
phenotype strongly correlated with phylogenetic relatedness, indicative of kin
discrimination. Using a subset of strains, we examined cocolonization patterns on
plant roots. Pairs of kin strains were able to cocolonize roots and formed a
mixed-strain biofilm. In contrast, inoculating roots with pairs of nonkin strains
resulted in biofilms consisting primarily of one strain, suggestive of an
antagonistic interaction among nonkin strains. This study firmly establishes kin
discrimination in a bacterial multicellular setting and suggests its potential
effect on ecological interactions.
PMID- 26438859
TI - Consequences of zygote injection and germline transfer of mutant human
mitochondrial DNA in mice.
AB - Considerable evidence supports mutations in mitochondrial genes as the cause of
maternally inherited diseases affecting tissues that rely primarily on oxidative
energy metabolism, usually the nervous system, the heart, and skeletal muscles.
Mitochondrial diseases are diverse, and animal models currently are limited. Here
we introduced a mutant human mitochondrial gene responsible for Leber hereditary
optic neuropathy (LHON) into the mouse germ line using fluorescence imaging for
tissue-specific enrichment in the target retinal ganglion cells. A mitochondria
targeted adeno-associated virus (MTS-AAV) containing the mutant human NADH
ubiquinone oxidoreductase subunit 4 (ND4) gene followed by mitochondrial-encoded
mCherry was microinjected into zygotes. Female founders with mCherry fluorescence
on ophthalmoscopy were backcrossed with normal males for eight generations.
Mutant human ND4 DNA was 20% of mouse ND4 and did not integrate into the host
genome. Translated human ND4 protein assembled into host respiratory complexes,
decreasing respiratory chain function and increasing oxidative stress. Swelling
of the optic nerve head was followed by progressive demise of ganglion cells and
their axons, the hallmarks of human LHON. Early visual loss that began at 3 mo
and progressed to blindness 8 mo after birth was reversed by intraocular
injection of MTS-AAV expressing wild-type human ND4. The technology of
introducing human mitochondrial genes into the mouse germ line has never been
described, to our knowledge, and has implications not only for creating animal
models recapitulating the counterpart human disorder but more importantly for
reversing the adverse effects of the mutant gene using gene therapy to deliver
the wild-type allele.
PMID- 26438860
TI - Variable genetic architectures produce virtually identical molecules in bacterial
symbionts of fungus-growing ants.
AB - Small molecules produced by Actinobacteria have played a prominent role in both
drug discovery and organic chemistry. As part of a larger study of the
actinobacterial symbionts of fungus-growing ants, we discovered a small family of
three previously unreported piperazic acid-containing cyclic depsipeptides,
gerumycins A-C. The gerumycins are slightly smaller versions of dentigerumycin, a
cyclic depsipeptide that selectively inhibits a common fungal pathogen,
Escovopsis. We had previously identified this molecule from a Pseudonocardia
associated with Apterostigma dentigerum, and now we report the molecule from an
associate of the more highly derived ant Trachymyrmex cornetzi. The three
previously unidentified compounds, gerumycins A-C, have essentially identical
structures and were produced by two different symbiotic Pseudonocardia spp. from
ants in the genus Apterostigma found in both Panama and Costa Rica. To understand
the similarities and differences in the biosynthetic pathways that produced these
closely related molecules, the genomes of the three producing Pseudonocardia were
sequenced and the biosynthetic gene clusters identified. This analysis revealed
that dramatically different biosynthetic architectures, including genomic
islands, a plasmid, and the use of spatially separated genetic loci, can lead to
molecules with virtually identical core structures. A plausible evolutionary
model that unifies these disparate architectures is presented.
PMID- 26438861
TI - Longitudinal spread of mechanical excitation through tectorial membrane traveling
waves.
AB - The mammalian inner ear separates sounds by their frequency content, and this
separation underlies important properties of human hearing, including our ability
to understand speech in noisy environments. Studies of genetic disorders of
hearing have demonstrated a link between frequency selectivity and wave
properties of the tectorial membrane (TM). To understand these wave properties
better, we developed chemical manipulations that systematically and reversibly
alter TM stiffness and viscosity. Using microfabricated shear probes, we show
that (i) reducing pH reduces TM stiffness with little change in TM viscosity and
(ii) adding PEG increases TM viscosity with little change in TM stiffness. By
applying these manipulations in measurements of TM waves, we show that TM wave
speed is determined primarily by stiffness at low frequencies and by viscosity at
high frequencies. Both TM viscosity and stiffness affect the longitudinal spread
of mechanical excitation through the TM over a broad range of frequencies.
Increasing TM viscosity or decreasing stiffness reduces longitudinal spread of
mechanical excitation, thereby coupling a smaller range of best frequencies and
sharpening tuning. In contrast, increasing viscous loss or decreasing stiffness
would tend to broaden tuning in resonance-based TM models. Thus, TM wave and
resonance mechanisms are fundamentally different in the way they control
frequency selectivity.
PMID- 26438862
TI - Effects of lymphocyte profile on development of EBV-induced lymphoma subtypes in
humanized mice.
AB - Epstein-Barr virus (EBV) infection causes both Hodgkin's lymphoma (HL) and non
Hodgkin's lymphoma (NHL). The present study reveals that EBV-induced HL and NHL
are intriguingly associated with a repopulated immune cell profile in humanized
mice. Newborn immunodeficient NSG mice were engrafted with human cord blood
CD34(+) hematopoietic stem cells (HSCs) for a 8- or 15-wk reconstitution period
(denoted (8w)hN and (15w)hN, respectively), resulting in human B-cell and T-cell
predominance in peripheral blood cells, respectively. Further, novel humanized
mice were established via engraftment of hCD34(+) HSCs together with
nonautologous fetal liver-derived mesenchymal stem cells (MSCs) or MSCs
expressing an active notch ligand DLK1, resulting in mice skewed with human B or
T cells, respectively. After EBV infection, whereas NHL developed more frequently
in B-cell-predominant humanized mice, HL was seen in T-cell-predominant mice (P =
0.0013). Whereas human splenocytes from NHL-bearing mice were positive for EBV
associated NHL markers (hBCL2(+), hCD20(+), hKi67(+), hCD20(+)/EBNA1(+), and
EBER(+)) but negative for HL markers (LMP1(-), EBNA2(-), and hCD30(-)), most HL
like tumors were characterized by the presence of malignant Hodgkin's Reed
Sternberg (HRS)-like cells, lacunar RS (hCD30(+), hCD15(+), IgJ(-),
EBER(+)/hCD30(+), EBNA1(+)/hCD30(+), LMP(+)/EBNA2(-), hCD68(+), hBCL2(-), hCD20(
/weak,) Phospho STAT6(+)), and mummified RS cells. This study reveals that immune
cell composition plays an important role in the development of EBV-induced B-cell
lymphoma.
PMID- 26438863
TI - Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum
fungicide.
AB - The unexpected resistance of psoriasis lesions to fungal infections suggests
local production of an antifungal factor. We purified Trichophyton rubrum
inhibiting activity from lesional psoriasis scale extracts and identified the Cys
reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor.
redS100A7 inhibits various filamentous fungi, including the mold Aspergillus
fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn(2+),
suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7
mutants lacking a single cysteine are no longer antifungals, we hypothesized that
redS100A7 is acting as a Zn(2+)-chelator. Immunogold electron microscopy studies
revealed that it penetrates fungal cells, implicating possible intracellular
actions. In support with our hypothesis, the cell-penetrating Zn(2+)-chelator
TPEN was found to function as a broad-spectrum antifungal. Ultrastructural
analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis,
suggesting that its mode of action is induction of programmed cell death. TUNEL,
SYTOX-green analyses, and caspase-inhibition studies supported this for both T.
rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7
by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin
infection indicate induction of both S100A7 and its reducing agent in vivo. To
investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea
pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus
infection model for lung infection and found antifungal activity in both in vivo
animal systems. Thus, selective fungal cell-penetrating Zn(2+)-chelators could be
useful as an urgently needed novel antifungal therapeutic, which induces
programmed cell death in numerous fungi.
PMID- 26438864
TI - Bubble nucleation and migration in a lead-iron hydr(oxide) core-shell
nanoparticle.
AB - Iron hydroxide is found in a wide range of contexts ranging from biominerals to
steel corrosion, and it can transform to anhydrous oxide via releasing O2 gas and
H2O. However, it is not well understood how gases transport through a crystal
lattice. Here, we present in situ observation of the nucleation and migration of
gas bubbles in iron (hydr)oxide using transmission electron microscopy. We create
Pb-FeOOH model core-shell nanoparticles in a liquid cell. Under electron
irradiation, iron hydroxide transforms to iron oxide, during which bubbles are
generated, and they migrate through the shell to the nanoparticle surface.
Geometric phase analysis of the shell lattice shows an inhomogeneous stain field
at the bubbles. Our modeling suggests that the elastic interaction between the
core and the bubble provides a driving force for bubble migration.
PMID- 26438865
TI - Melanopsin-driven increases in maintained activity enhance thalamic visual
response reliability across a simulated dawn.
AB - Twice a day, at dawn and dusk, we experience gradual but very high amplitude
changes in background light intensity (irradiance). Although we perceive the
associated change in environmental brightness, the representation of such very
slow alterations in irradiance by the early visual system has been little
studied. Here, we addressed this deficit by recording electrophysiological
activity in the mouse dorsal lateral geniculate nucleus under exposure to a
simulated dawn. As irradiance increased we found a widespread enhancement in
baseline firing that extended to units with ON as well as OFF responses to fast
luminance increments. This change in baseline firing was equally apparent when
the slow irradiance ramp appeared alone or when a variety of higher-frequency
artificial or natural visual stimuli were superimposed upon it. Using a
combination of conventional knockout, chemogenetic, and receptor-silent
substitution manipulations, we continued to show that, over higher irradiances,
this increase in firing originates with inner-retinal melanopsin photoreception.
At the single-unit level, irradiance-dependent increases in baseline firing were
strongly correlated with improvements in the amplitude of responses to higher
frequency visual stimuli. This in turn results in an up to threefold increase in
single-trial reliability of fast visual responses. In this way, our data indicate
that melanopsin drives a generalized increase in dorsal lateral geniculate
nucleus excitability as dawn progresses that both conveys information about
changing background light intensity and increases the signal:noise for fast
visual responses.
PMID- 26438866
TI - 90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of
patients with relapsed Hodgkin's lymphoma.
AB - Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a
significant proportion of patients will not respond or will subsequently relapse.
We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for
systemic radioimmunotherapy of HL. The scientific basis for the clinical trial
was that, although most normal cells with exception of Treg cells do not express
CD25, it is expressed by a minority of Reed-Sternberg cells and by most
polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with
refractory and relapsed HL were evaluated with up to seven i.v. infusions of the
radiolabeled anti-CD25 antibody (90)Y-daclizumab. (90)Y provides strong beta
emissions that kill tumor cells at a distance by a crossfire effect. In 46
evaluable HL patients treated with (90)Y-daclizumab there were 14 complete
responses and nine partial responses; 14 patients had stable disease, and nine
progressed. Responses were observed both in patients whose Reed-Sternberg cells
expressed CD25 and in those whose neoplastic cells were CD25(-) provided that
associated rosetting T cells expressed CD25. As assessed using phosphorylated
H2AX (gamma-H2AX) as a bioindicator of the effects of radiation exposure,
predominantly nonmalignant cells in the tumor microenvironment manifested DNA
damage, as reflected by increased expression of gamma-H2AX. Toxicities were
transient bone-marrow suppression and myelodysplastic syndrome in six patients
who had not been evaluated with bone-marrow karyotype analyses before therapy. In
conclusion, repeated (90)Y-daclizumab infusions directed predominantly toward
nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful
therapy for select HL patients.
PMID- 26438867
TI - Peptidoglycan synthesis in Mycobacterium tuberculosis is organized into networks
with varying drug susceptibility.
AB - Peptidoglycan (PG), a complex polymer composed of saccharide chains cross-linked
by short peptides, is a critical component of the bacterial cell wall. PG
synthesis has been extensively studied in model organisms but remains poorly
understood in mycobacteria, a genus that includes the important human pathogen
Mycobacterium tuberculosis (Mtb). The principle PG synthetic enzymes have similar
and, at times, overlapping functions. To determine how these are functionally
organized, we carried out whole-genome transposon mutagenesis screens in Mtb
strains deleted for ponA1, ponA2, and ldtB, major PG synthetic enzymes. We
identified distinct factors required to sustain bacterial growth in the absence
of each of these enzymes. We find that even the homologs PonA1 and PonA2 have
unique sets of genetic interactions, suggesting there are distinct PG synthesis
pathways in Mtb. Either PonA1 or PonA2 is required for growth of Mtb, but both
genetically interact with LdtB, which has its own distinct genetic network. We
further provide evidence that each interaction network is differentially
susceptible to antibiotics. Thus, Mtb uses alternative pathways to produce PG,
each with its own biochemical characteristics and vulnerabilities.
PMID- 26438868
TI - Glycoprotein B7-H3 overexpression and aberrant glycosylation in oral cancer and
immune response.
AB - The incidence and mortality rate of oral cancer continue to rise, partly due to
the lack of effective early diagnosis and increasing environmental exposure to
cancer-causing agents. To identify new markers for oral cancer, we used a
sialylation probe to investigate the glycoproteins differentially expressed on
oral cancer cells. Of the glycoproteins identified, B7 Homolog 3 (B7-H3) was
significantly overexpressed in oral squamous cell carcinoma (OSCC), and its
overexpression correlated with larger tumor size, advanced clinical stage, and
low survival rate in OSCC patients. In addition, knockdown of B7-H3 suppressed
tumor cell proliferation, and restoration of B7-H3 expression enhanced tumor
growth. It was also found that the N-glycans of B7-H3 from Ca9-22 oral cancer
cells contain the terminal alpha-galactose and are more diverse with higher
fucosylation and better interaction with DC-SIGN [DC-specific intercellular
adhesion molecule-3 (ICAM-3)-grabbing nonintegrin] and Langerin on immune cells
than that from normal cells, suggesting that the glycans on B7-H3 may also play
an important role in the disease.
PMID- 26438869
TI - Power decreases trust in social exchange.
AB - How does lacking vs. possessing power in a social exchange affect people's trust
in their exchange partner? An answer to this question has broad implications for
a number of exchange settings in which dependence plays an important role. Here,
we report on a series of experiments in which we manipulated participants' power
position in terms of structural dependence and observed their trust perceptions
and behaviors. Over a variety of different experimental paradigms and measures,
we find that more powerful actors place less trust in others than less powerful
actors do. Our results contradict predictions by rational actor models, which
assume that low-power individuals are able to anticipate that a more powerful
exchange partner will place little value on the relationship with them, thus
tends to behave opportunistically, and consequently cannot be trusted.
Conversely, our results support predictions by motivated cognition theory, which
posits that low-power individuals want their exchange partner to be trustworthy
and then act according to that desire. Mediation analyses show that, consistent
with the motivated cognition account, having low power increases individuals'
hope and, in turn, their perceptions of their exchange partners' benevolence,
which ultimately leads them to trust.
PMID- 26438870
TI - Algal ancestor of land plants was preadapted for symbiosis.
AB - Colonization of land by plants was a major transition on Earth, but the
developmental and genetic innovations required for this transition remain
unknown. Physiological studies and the fossil record strongly suggest that the
ability of the first land plants to form symbiotic associations with beneficial
fungi was one of these critical innovations. In angiosperms, genes required for
the perception and transduction of diffusible fungal signals for root
colonization and for nutrient exchange have been characterized. However, the
origin of these genes and their potential correlation with land colonization
remain elusive. A comprehensive phylogenetic analysis of 259 transcriptomes and
10 green algal and basal land plant genomes, coupled with the characterization of
the evolutionary path leading to the appearance of a key regulator, a calcium-
and calmodulin-dependent protein kinase, showed that the symbiotic signaling
pathway predated the first land plants. In contrast, downstream genes required
for root colonization and their specific expression pattern probably appeared
subsequent to the colonization of land. We conclude that the most recent common
ancestor of extant land plants and green algae was preadapted for symbiotic
associations. Subsequent improvement of this precursor stage in early land plants
through rounds of gene duplication led to the acquisition of additional pathways
and the ability to form a fully functional arbuscular mycorrhizal symbiosis.
PMID- 26438871
TI - Population genomic structure and adaptation in the zoonotic malaria parasite
Plasmodium knowlesi.
AB - Malaria cases caused by the zoonotic parasite Plasmodium knowlesi are being
increasingly reported throughout Southeast Asia and in travelers returning from
the region. To test for evidence of signatures of selection or unusual population
structure in this parasite, we surveyed genome sequence diversity in 48 clinical
isolates recently sampled from Malaysian Borneo and in five lines maintained in
laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia
and the Philippines. Overall genomewide nucleotide diversity (pi = 6.03 * 10(-3))
was much higher than has been seen in worldwide samples of either of the major
endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A
remarkable substructure is revealed within P. knowlesi, consisting of two major
sympatric clusters of the clinical isolates and a third cluster comprising the
laboratory isolates. There was deep differentiation between the two clusters of
clinical isolates [mean genomewide fixation index (FST) = 0.21, with 9,293 SNPs
having fixed differences of FST = 1.0]. This differentiation showed marked
heterogeneity across the genome, with mean FST values of different chromosomes
ranging from 0.08 to 0.34 and with further significant variation across regions
within several chromosomes. Analysis of the largest cluster (cluster 1, 38
isolates) indicated long-term population growth, with negatively skewed allele
frequency distributions (genomewide average Tajima's D = -1.35). Against this
background there was evidence of balancing selection on particular genes,
including the circumsporozoite protein (csp) gene, which had the top Tajima's D
value (1.57), and scans of haplotype homozygosity implicate several genomic
regions as being under recent positive selection.
PMID- 26438872
TI - Rapid Y degeneration and dosage compensation in plant sex chromosomes.
AB - The nonrecombining regions of animal Y chromosomes are known to undergo genetic
degeneration, but previous work has failed to reveal large-scale gene
degeneration on plant Y chromosomes. Here, we uncover rapid and extensive
degeneration of Y-linked genes in a plant species, Silene latifolia, that evolved
sex chromosomes de novo in the last 10 million years. Previous transcriptome
based studies of this species missed unexpressed, degenerate Y-linked genes. To
identify sex-linked genes, regardless of their expression, we sequenced male and
female genomes of S. latifolia and integrated the genomic contigs with a high
density genetic map. This revealed that 45% of Y-linked genes are not expressed,
and 23% are interrupted by premature stop codons. This contrasts with X-linked
genes, in which only 1.3% of genes contained stop codons and 4.3% of genes were
not expressed in males. Loss of functional Y-linked genes is partly compensated
for by gene-specific up-regulation of X-linked genes. Our results demonstrate
that the rate of genetic degeneration of Y-linked genes in S. latifolia is as
fast as in animals, and that the evolutionary trajectories of sex chromosomes are
similar in the two kingdoms.
PMID- 26438873
TI - Expected time-invariant effects of biological traits on mammal species duration.
AB - Determining which biological traits influence differences in extinction risk is
vital for understanding the differential diversification of life and for making
predictions about species' vulnerability to anthropogenic impacts. Here I present
a hierarchical Bayesian survival model of North American Cenozoic mammal species
durations in relation to species-level ecological factors, time of origination,
and phylogenetic relationships. I find support for the survival of the
unspecialized as a time-invariant generalization of trait-based extinction risk.
Furthermore, I find that phylogenetic and temporal effects are both substantial
factors associated with differences in species durations. Finally, I find that
the estimated effects of these factors are partially incongruous with how these
factors are correlated with extinction risk of the extant species. These findings
parallel previous observations that background extinction is a poor predictor of
mass extinction events and suggest that attention should be focused on mass
extinctions to gain insight into modern species loss.
PMID- 26438874
TI - Mechanism for rapid passive-dynamic prey capture in a pitcher plant.
AB - Plants use rapid movements to disperse seed, spores, or pollen and catch animal
prey. Most rapid-release mechanisms only work once and, if repeatable, regaining
the prerelease state is a slow and costly process. We present an encompassing
mechanism for a rapid, repeatable, passive-dynamic motion used by a carnivorous
pitcher plant to catch prey. Nepenthes gracilis uses the impact of rain drops to
catapult insects from the underside of the canopy-like pitcher lid into the fluid
filled trap below. High-speed video and laser vibrometry revealed that the lid
acts as a torsional spring system, driven by rain drops. During the initial
downstroke, the tip of the lid reached peak velocities similar to fast animal
motions and an order of magnitude faster than the snap traps of Venus flytraps
and catapulting tentacles of the sundew Drosera glanduligera. In contrast to
these active movements, the N. gracilis lid oscillation requires neither
mechanical preloading nor metabolic energy, and its repeatability is only limited
by the intensity and duration of rainfall. The underside of the lid is coated
with friction-reducing wax crystals, making insects more vulnerable to
perturbations. We show that the trapping success of N. gracilis relies on the
combination of material stiffness adapted for momentum transfer and the
antiadhesive properties of the wax crystal surface. The impact-driven oscillation
of the N. gracilis lid represents a new kind of rapid plant movement with
adaptive function. Our findings establish the existence of a continuum between
active and passive trapping mechanisms in carnivorous plants.
PMID- 26438875
TI - A runner's high depends on cannabinoid receptors in mice.
AB - Exercise is rewarding, and long-distance runners have described a runner's high
as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A
popular belief has been that endogenous endorphins mediate these beneficial
effects. However, running exercise increases blood levels of both beta-endorphin
(an opioid) and anandamide (an endocannabinoid). Using a combination of
pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate
that cannabinoid receptors mediate acute anxiolysis and analgesia after running.
We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors
on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1
and CB2 receptors. We thus demonstrate that the endocannabinoid system is crucial
for two main aspects of a runner's high. Sedation, in contrast, was not
influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be
studied in mouse models.
PMID- 26438876
TI - Direct link between metabolic regulation and the heat-shock response through the
transcriptional regulator PGC-1alpha.
AB - In recent years an extensive effort has been made to elucidate the molecular
pathways involved in metabolic signaling in health and disease. Here we show,
surprisingly, that metabolic regulation and the heat-shock/stress response are
directly linked. Peroxisome proliferator-activated receptor gamma coactivator
1alpha (PGC-1alpha), a critical transcriptional coactivator of metabolic genes,
acts as a direct transcriptional repressor of heat-shock factor 1 (HSF1), a key
regulator of the heat-shock/stress response. Our findings reveal that heat-shock
protein (HSP) gene expression is suppressed during fasting in mouse liver and in
primary hepatocytes dependent on PGC-1alpha. HSF1 and PGC-1alpha associate
physically and are colocalized on several HSP promoters. These observations are
extended to several cancer cell lines in which PGC-1alpha is shown to repress the
ability of HSF1 to activate gene-expression programs necessary for cancer
survival. Our study reveals a surprising direct link between two major cellular
transcriptional networks, highlighting a previously unrecognized facet of the
activity of the central metabolic regulator PGC-1alpha beyond its well
established ability to boost metabolic genes via its interactions with nuclear
hormone receptors and nuclear respiratory factors. Our data point to PGC-1alpha
as a critical repressor of HSF1-mediated transcriptional programs, a finding with
possible implications both for our understanding of the full scope of
metabolically regulated target genes in vivo and, conceivably, for therapeutics.
PMID- 26438877
TI - Brain palpation from physiological vibrations using MRI.
AB - We present a magnetic resonance elastography approach for tissue characterization
that is inspired by seismic noise correlation and time reversal. The idea
consists of extracting the elasticity from the natural shear waves in living
tissues that are caused by cardiac motion, blood pulsatility, and any muscle
activity. In contrast to other magnetic resonance elastography techniques, this
noise-based approach is, thus, passive and broadband and does not need any
synchronization with sources. The experimental demonstration is conducted in a
calibrated phantom and in vivo in the brain of two healthy volunteers. Potential
applications of this "brain palpation" approach for characterizing brain
anomalies and diseases are foreseen.
PMID- 26438878
TI - Structure and function of Caulobacter crescentus aldose-aldose oxidoreductase.
AB - Aldose-aldose oxidoreductase (Cc AAOR) is a recently characterized enzyme from
the bacterial strain Caulobacter crescentus CB15 belonging to the glucose
fructose oxidoreductase/inositol dehydrogenase/rhizopine catabolism protein
(Gfo/Idh/MocA) family. Cc AAOR catalyses the oxidation and reduction of a panel
of aldose monosaccharides using a tightly bound NADP(H) cofactor that is
regenerated in the catalytic cycle. Furthermore, Cc AAOR can also oxidize 1,4
linked oligosaccharides. In the present study, we present novel crystal
structures of the dimeric Cc AAOR in complex with the cofactor and glycerol, D
xylose, D-glucose, maltotriose and D-sorbitol determined to resolutions of 2.0,
1.8, 1.7, 1.9 and 1.8 A (1 A=0.1 nm), respectively. These complex structures
allowed for a detailed analysis of the ligand-binding interactions. The
structures showed that the C1 carbon of a substrate, which is either reduced or
oxidized, is close to the reactive C4 carbon of the nicotinamide ring of NADP(H).
In addition, the O1 hydroxy group of the substrate, which is either protonated or
deprotonated, is unexpectedly close to both Lys(104) and Tyr(189), which may both
act as a proton donor or acceptor. This led us to hypothesize that this
intriguing feature could be beneficial for Cc AAOR to catalyse the reduction of a
linear form of a monosaccharide substrate and the oxidation of a pyranose form of
the same substrate in a reaction cycle, during which the bound cofactor is
regenerated.
PMID- 26438879
TI - Biophysical and physiological characterization of ZraP from Escherichia coli, the
periplasmic accessory protein of the atypical ZraSR two-component system.
AB - The ZraSR system belongs to the family of TCSs (two-component signal transduction
systems). In Escherichia coli, it was proposed to participate in zinc balance and
to protect cytoplasmic zinc overload by sequestering this metal ion into the
periplasm. This system controls the expression of the accessory protein ZraP that
would be a periplasmic zinc scavenger. ZraPSR is functionally homologous with
CpxPAR that integrates signals of envelope perturbation, including misfolded
periplasmic proteins. The auxiliary periplasmic regulator CpxP inhibits the Cpx
pathway by interacting with CpxA. Upon envelope stress sensing, the inhibitory
function of CpxP is relieved, resulting in CpxR activation. Similarly to CpxPAR,
ZraPSR probably plays a role in envelope stress response as a zinc-dependent
chaperone activity was demonstrated for ZraP in Salmonella. We have purified ZraP
from E. coli and shown that it is an octamer containing four interfacial metal
binding sites contributing to dimer stability. These sites are located close to
the N-terminus, whereas the C-terminus is involved in polymerization of the
protein to form a tetramer of dimers. In vitro, ZraP binds copper with a higher
affinity than zinc and displays chaperone properties partially dependent on zinc
binding. In vivo, zinc-bound ZraP is a repressor of the expression of the zraPSR
operon. However, we have demonstrated that none of the Zra proteins are involved
in zinc or copper resistance. We propose an integrated mechanism in which zinc is
a marker of envelope stress perturbation and ZraPSR TCS is a sentinel sensing and
responding to zinc entry into the periplasm.
PMID- 26438882
TI - Holocord syrinx associated with haemangioblastoma.
PMID- 26438880
TI - Adipocyte-derived PAMM suppresses macrophage inflammation by inhibiting MAPK
signalling.
AB - Macrophages within adipose tissue play a key role in mediating inflammatory
responses in adipose tissue that are associated with obesity-related metabolic
complications. In an effort to identify novel proteins secreted from adipocytes
that may negatively regulate macrophage inflammation, we found that peroxiredoxin
(PRX)-like 2 activated in M-CSF stimulated monocytes (PAMM), a CXXC-type PRX-like
2 domain-containing redox regulatory protein, is a novel secreted protein with
potent anti-inflammatory properties. PAMM is secreted from mature human
adipocytes but not preadipocytes. Overexpression of PAMM significantly attenuated
lipopolysaccharide (LPS)-induced macrophage inflammation. Incubation of
macrophages with adipocyte-conditional medium treated with anti-PAMM antibody
significantly enhanced LPS-induced interleukin-12 (IL-12) expression in Raw264.7
cells. In addition, incubation of Raw264.7 cells with purified PAMM protein had a
similar anti-inflammatory effect. Moreover, forced expression of PAMM in Raw264.7
cells resulted in decreased LPS-induced ERK1/2, p38 and c-Jun N-terminal kinase
(JNK) phosphorylation, suggesting that PAMM exerted the anti-inflammatory
function probably by suppressing the mitogen-activated protein kinase (MAPK)
signalling pathway. Mutations in the CXXC motif of PAMM that suppressed its anti
redox activity were still able to suppress production of inflammatory cytokines
in LPS-stimulated macrophages, suggesting that PAMM's anti-inflammatory
properties may be independent of its antioxidant properties. Finally, PAMM was
highly expressed in both white (WAT) and brown adipose tissues (BAT) and further
increased in obesity status. Our results suggest that adipocyte-derived PAMM may
suppress macrophage activation by inhibiting MAPK signalling pathway.
PMID- 26438881
TI - Consequences of postnatal vascular smooth muscle EGFR deletion on acute
angiotensin II action.
AB - Epi dermal growth factor (EGF) receptor (EGFR) is activated by its canonical
ligands and transactivated by various vasoactive substances, e.g. angiotensin II
(Ang II). Vascular EGFR has been proposed to be involved in vascular tissue
homoeostasis and remodelling. Thus, most studies have focused on its role during
long-term vascular changes whereas the relevance for acute regulation of vascular
function in vivo and ex vivo is insufficiently understood. To investigate the
postnatal role of VSMCs (vascular smooth muscle cells) EGFR in vivo and ex vivo,
we generated a mouse model with cell-specific and inducible deletion of VSMC EGFR
and studied the effect on basal blood pressure, acute pressure response to, among
others, Ang II in vivo as well as ex vivo, cardiovascular tissue homoeostasis and
vessel morphometry in male mice. In knockout (KO) animals, systolic, diastolic
and mean blood pressures were reduced compared with wild-type (WT). Furthermore,
Ang II-induced pressure load was lower in KO animals, as was Ang II-induced force
development and extracellular-signal-regulated kinase 1 and 2 (ERK1/2)
phosphorylation in aortic rings from KO animals. By contrast, we observed no
difference in force development during application of serotonin, KCl, endothelin
1 or endothelin-1-induced pressure load in KO animals. In addition, nitric oxide
(NO)-mediated vasodilation was not affected. Heart weight (HW) increase and up
regulation of aortic and cardiac expression of Ccl2 (chemoattractant protein-2)
and serpinE1 (plasminogen activator inhibitor 1) during the transition from 4- to
10-months of age were prevented by VSMC EGFR KO. We conclude that VSMC EGFR is
involved in basal blood pressure homoeostasis and acute pressure response to Ang
II, and thereby contributes to maturation-related remodelling.
PMID- 26438883
TI - Neurological letter from Italy.
PMID- 26438884
TI - Role of emotional competence in residents' simulated emergency care performance:
a mixed-methods study.
AB - OBJECTIVE: Emergency situations can generate negative affect in medical
personnel, which can negatively impact on the quality of care. Several studies
have demonstrated a positive influence of emotional competence (EC) on negative
affect. The goal of this study was to test the effect of EC level on simulated
emergency care situation in medical residents. METHODS: The sample included 21
medical residents caring for a simulated seriously wounded person whose condition
suddenly deteriorated. Medical performance was scored by expert medical doctors
(MDs). EC level and affective states were evaluated with self-assessment
questionnaires. Finally, the origin of the negative affect experienced by the
residents was identified through individual interviews. RESULTS: Higher EC levels
were found to be associated with better medical performance and a lower intensity
of negative affect. The latter two variables were found to correlate negatively.
The main source of negative affect for residents was the inability to establish a
diagnosis, regardless of their EC level and their medical performance.
CONCLUSIONS: The results suggest that residents who have a high EC level are
better able to manage negative affect, so that they are better able to put their
medical knowledge to work and explore alternative diagnoses. Emotional-management
training for residents who, as new MDs, have limited experience may be beneficial
to complement simulation exercises. Additional studies should be considered to
better define the links between the affect experienced by MDs and their thought
processes during establishment of a diagnosis.
PMID- 26438890
TI - Gold nanodome-patterned microchips for intracellular surface-enhanced Raman
spectroscopy.
AB - While top-down substrates for surface-enhanced Raman spectroscopy (SERS) offer
outstanding control and reproducibility of the gold nanopatterns and their
related localized surface plasmon resonance, intracellular SERS experiments
heavily rely on gold nanoparticles. These nanoparticles often result in varying
and uncontrollable enhancement factors. Here we demonstrate the use of top-down
gold-nanostructured microchips for intracellular sensing. We develop a tunable
and reproducible fabrication scheme for these microchips. Furthermore we observe
the intracellular uptake of these structures, and find no immediate influence on
cell viability. Finally, we perform a proof-of-concept intracellular SERS
experiment by the label-free detection of extraneous molecules. By bringing top
down SERS substrates to the intracellular world, we set an important step towards
time-dependent and quantitative intracellular SERS.
PMID- 26438891
TI - Dual acid-responsive supramolecular nanoparticles as new anticancer drug delivery
systems.
AB - Considering the specific pH gradients of tumour microenvironments, a dual acid
responsive drug delivery system, which can respond to the tumor extracellular and
intercellular pH stimuli, has been fabricated via simple host-guest recognition.
Firstly, we synthesise 2,4,6-trimethoxybenzaldehyde modified dextran (Dex-TMBA)
and mPEG-imine-beta-cyclodextrin (PIC), respectively. And then, through the host
guest recognition between the cyclodextrin (CD) of PIC and the benzene ring of
Dex-TMBA, a kind of dual acid-responsive supramolecular drug delivery system can
be fabricated. Under neutral pH conditions, anticancer drugs can be loaded by
forming supramolecular nanoparticles via the host-guest recognition. While, at
tumor extracellular pH (~6.8), the acid-labile benzoic-imine of PIC cleaves and
the nanoparticles are amino positively charged to facilitate cell
internalization. Subsequently, due to the hydrolysis of acetal bonds in Dex-TMBA
under significantly increased acidity in subcellular compartments such as the
endosomes (~5.3), the loaded doxorubicin releases from the endocytosed drug
delivery. This dual acid-responsive nanoparticles can efficiently load and
release drugs, acting as drug delivery systems for enhancing anticancer
efficiency.
PMID- 26438893
TI - Mark Gorney, M.D., 1924 to 2014.
PMID- 26438894
TI - The Seventh Annual Meeting of the European Plastic Surgery Research Council.
PMID- 26438892
TI - Single-molecule observations of RNA-RNA kissing interactions in a DNA
nanostructure.
AB - RNA molecules uniquely form a complex through specific hairpin loops, called a
kissing complex. The kissing complex is widely investigated and used for the
construction of RNA nanostructures. Molecular switches have also been created by
combining a kissing loop and a ligand-binding aptamer to control the interactions
of RNA molecules. In this study, we incorporated two kinds of RNA molecules into
a DNA origami structure and used atomic force microscopy to observe their ligand
responsive interactions at the single-molecule level. We used a designed RNA
aptamer called GTPswitch, which has a guanosine triphosphate (GTP) responsive
domain and can bind to the target RNA hairpin named Aptakiss in the presence of
GTP. We observed shape changes of the DNA/RNA strands in the DNA origami, which
are induced by the GTPswitch, into two different shapes in the absence and
presence of GTP, respectively. We also found that the switching function in the
nanospace could be improved by using a cover strand over the kissing loop of the
GTPswitch or by deleting one base from this kissing loop. These newly designed
ligand-responsive aptamers can be used for the controlled assembly of the various
DNA and RNA nanostructures.
PMID- 26438895
TI - Welcome from the Captain.
PMID- 26438896
TI - Obituary: Dr. Yoshihito Otsuji.
PMID- 26438897
TI - [Cognitive impairments in psychoactive drug addicts].
AB - This short literature review addresses common features of the pathogenesis and
treatment of cognitive impairment in people with drug addiction (cocaine,
opioids, hashish, amphetamine, benzodiazepines). A role of cholinergic deficit in
the development of cognitive impairment and possibilities of its treatment with
acetylcholineesterase inhibitions are analyzed.
PMID- 26438898
TI - [Molecular aspects of the pathogenesis and current approaches to pharmacological
correction of Alzheimer's disease].
AB - This review addresses the current hypotheses of the pathogenesis of Alzheimer's
disease (AD) and methods of its pharmacological corrections. The following topics
are reviewed: a role of beta-amyloid in the pathogenesis of AD, a role of tau
protein in the pathogenesis of AD, main hypotheses of the pathogenesis, the
relationship between beta-amyloid and tau-protein, the dysfunction of synapses in
AD, a neuroimmune hypothesis, treatment approaches.
PMID- 26438902
TI - Redefining acute care surgery: Surgical rescue.
PMID- 26438903
TI - [Molecular-genetic and electroencephalographic markers of neurocognitive
processes in depressive disorders].
AB - Perspectives of molecular-genetic approaches to the establishment of mechanisms
of development and causes of heterogeneity of neurocognitive impairment are
discussed. The current results indicate that candidate genes for depression can
contribute to the variance of memory and regulatory functions in patients. At the
same time, these genes are closely related to affective information processing
and .cortisol level. By that fact, it can't be excluded that affective processes
moderate the association between cognition and genes. EEG parameters could be
useful phenotypes in the search for and understanding of genetic mechanisms of
cognitive deficit in depression. Parameters of resting EEG and its reactive
changes are known to reflect the certain cognitive processes. They are influenced
by genetic factors and are sensitive indicators of mechanisms that might underlie
cognitive impairment in depressive patients. Accumulating data on molecular
genetic correlates of normal electric brain activity may be a source of choosing
new candidate genes for cognitive impairment in depression.
PMID- 26438904
TI - [Central and peripheral vestibular vertigo in neurological practice].
AB - This literature review is devoted to the differential diagnosis of central and
peripheral vestibular vertigo from the point of view of modern otoneurology. In
addition, an own case is given.
PMID- 26438905
TI - [New possibilities of monotherapy of symptomatic and cryptogenic partial
epilepsy].
AB - This literature review is devoted to the use of the antiepileptic drug zonisamide
in the initial monotherapy of symptomatic and cryptogenic partial epilepsy. The
review is based on the results of the trials, level of evidence A, that
demonstrate the efficacy and tolerability of zonisamide comparable to those of
carbamazepine. The possible advantages of zonisamide in different clinical
situations and characteristics of its use related to molecule structure,
pharmacokinetics, mechanisms of drug action are discussed.
PMID- 26438906
TI - [By 120-th anniversary of Orel regional psychiatric hospital].
PMID- 26438908
TI - Retraction notice to "Identifying halophilic proteins based on random forests
with preprocessing of the pseudo-amino acid composition" [J. Theor. Biol. 361
(2014) 175-181].
AB - This article has been retracted: please see Elsevier Policy on Article Withdrawal
(http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted
at the request of the authors. When using the resampling method to preprocess the
raw data of the paper used, some of the types of the proteins (i.e., the HI, HO
and NP) were changed; thus, the predicting accuracy cannot reflect the real
results. This means the effectiveness of resampling methods in this article gives
false results. The Publisher apologizes for any inconvenience this may cause.
PMID- 26438907
TI - [Stenosis of the vertebral canal in the lower spine].
AB - The article reviews modern literature on the pathophysiology and clinical signs
of degenerative stenosis of the lower spine. Possibilities of modern instrumental
diagnosis and the differential clinical diagnosis of lumbar stenosis are
presented. A modern treatment tactics and indications for surgical treatment are
described. A brief and schematic description of the methods of surgical treatment
of tenosis is presented. The efficacy of surgical treatment, including remote and
results in early patients, is discussed.
PMID- 26438909
TI - Reply from the Author.
PMID- 26438910
TI - Tough choices: the challenge of being a vet in an earthquake-stricken country.
PMID- 26438912
TI - NEW REPORT SHOWS THAT 400 MILLION DO NOT HAVE ACCESS TO ESSENTIAL HEALTH
SERVICES.
PMID- 26438911
TI - WHO VALIDATES ELIMINATION OF MOTHER-TO-CHILD TRANSMISSION OF HIV AND SYPHILIS IN
CUBA.
PMID- 26438913
TI - Breaking down barriers in India.
PMID- 26438915
TI - Practical management of strangles outbreaks in horses.
PMID- 26438914
TI - Happy 90th birthday AVJ.
PMID- 26438916
TI - Re: The Animal Protection Index.
PMID- 26438917
TI - Announcement of 2016 Special Issue: The behavioural pharmacology of oxytocin.
PMID- 26438918
TI - A morphology-based phylogeny of the Liolaemus alticolor-bibronii group (Iguania:
Liolaemidae).
AB - The genus Liolaemus was split in two subgenera, Liolaenus sensu stricto and
Eulaemus. Inside the Liolaemus sensu stricto subgenus, many groups have been
proposed. One of them is the L. alticolor-bibronii group. Here, I studied 184
morpho- logical characters of more than one thousand specimens that of the L.
alticolor-bibronii group. Many of these characters are original from this study,
especially the characters related to color pattern. Also, I include eight
population without tax- onomic status. Using those characters and terminal taxa,
I performed phylogenetic analyses using parsimony as optimality criterion, under
implied weight. Two different topologies were found. The results show that the L.
alticolor-bibronii group is monophyletic, and that it is sister to the L.
gravenhorsti group. This finding is congruent with previous morphological and
molecular phylogenies. Also, nested within the L. alticolor-bibronii group the L.
lemniscatus and the L. robertmen- tensi groups are found. In contrast to previous
hypotheses, Liolaemus tacnae is never recovered as a member of the L. alticolor
bibronii group.
PMID- 26438919
TI - A new species of Leptolalax (Anura: Megophryidae) from Gunung Mulu National Park,
Sarawak, East Malaysia (Borneo).
AB - We describe a new species of Leptolalax from Gunung Mulu National Park in eastern
Sarawak, Malaysian Borneo. The new species had been assigned to Leptolalax dringi
and Leptolalax gracilis in the past. It is shown to differ from both these
species and from all other species of the genus by a unique combination of
morphological characters including large body size, rounded snout, interorbital
distance being smaller than width of upper eyelid, bipartite subgular vocal sac
in males, basal toe webbing, shagreened skin with tiny tubercles on dorsum and
dorsal side of head, angled supratympanic fold, small pectoral glands, absence of
supraaxillary glands and ventrolateral glandular ridges, spotted venter,
advertisement call consisting of long series of 8-289 notes, each composed of
three or four pulses, and dominant frequency at 7225-9190 Hz, with prominent
frequency modulation.
PMID- 26438920
TI - New occurrences of lithodid crabs (Crustacea: Decapoda: Lithodidae) from the
coasts of Africa, with the description of a new species of Paralomis White, 1856.
AB - The Collection of Decapod and Stomatopod Crustaceans from the Cadiz Oceanographic
Centre (CCDE-IEOCD) comprises a number of lithodid crabs from Spanish surveys
carried out in African waters. The revision of this material allowed the
confirmation of new records of Lithodesferox Filhol, 1885 in Guinea-Bissau and
Mauritania, Lithodes mamillifer Macpherson, 1988 in Mozambique, Neolithodes
asperrimus Barnard, 1947, Neolithodes grimaldii (A. Milne Edwards & Bouvier,
1894) and Paralomis erinacea Macpherson, 1988 in Mauritania, Paralomis africana
Macpherson, 1982 in Namibia and Paralomis cristulata Macpherson, 1988 in Guinea
Bissau. Some of these records contribute to extent the geographical and/or
bathymetrical range of the species. One new species of the genus Paralomis from
Namibia is described and illustrated. This species shows close affinity with its
congener Paralomis pectinata Macpherson, 1988, from Venezuela. The morphological
differences between the two species are included.
PMID- 26438921
TI - A long-lost relic from the Eastern Ghats: Morphology, distribution and habitat of
Sepsophis punctatus Beddome, 1870 (Squamata: Scincidae).
AB - Sepsophis punctatus Beddome 1870, the only species of a monotypic genus, was
described based on a single specimen from the Eastern Ghats of India. We
rediscovered the species based on specimens from Odisha and Andhra Pradesh state,
India, after a gap of 137 years, including four specimens from close to the type
locality. The holotype was studied in detail, and we present additional
morphological characters of the species with details on natural history, habitat
and diet. The morphological characters of the holotype along with two additional
specimens collected by Beddome are compared with the specimens collected by us.
We also briefly discuss the distribution of other members of the subfamily
Scincinae and their evolutionary affinities.
PMID- 26438922
TI - Two new species of Psephenops Grouvelle from Belize (Coleoptera: Byrrhoidea:
Psephenidae), with a key to the known species from Mexico and Central America.
AB - Two new species, Psephenops spiniparameri sp. nov. and P. shepardi sp. nov. are
described, based on specimens collected from Cayo and Toledo Districts in Belize,
bringing the total number of described species assigned to the genus to ten.
PMID- 26438923
TI - Sarcophaga (Hoa)flexuosa Ho (Diptera: Sarcophagidae): association of sexes using
morphological and molecular approaches, and a redefinition of Hoa Rohdendorf.
AB - Sarcophaga flexuosa Ho, 1934 is the type species of the currently monotypic genus
group taxon Hoa Rohdendorf, 1937, which here is considered a subgenus of
Sarcophaga Meigen, 1826. Using DNA sequences of mitochondrial genes (cytochrome
oxidase I and cytochrome b), we positively identify, for the first time, the
female of S. (H.)flexuosa. The female is described, the male is redescribed, and
both sexes are illustrated using a combination of line drawings, photographs and
scanning electron microscopy images. It is argued from the morphology of the male
terminalia that Sarcophagaflexuosa is the sister taxon of Sarcophaga basiseta
Baranov, 1931, and the subgenus Hoa is redefined to include both of these
species.
PMID- 26438924
TI - Five new species of Baeus Haliday, 1833 (Hymenoptera: Platygastroidea:
Scelioninae) from Brazil with an updated key to Neotropical species.
AB - The species of the genus Baeus are small endoparasitoids wasps that attack
spiders' egg sacs. Although there are data of occurrence in several
biogeographical regions, their distribution records are scarce, especially due to
their small size, mak- ing difficult to collect them in natural environments. In
this paper, five new species of Baeus are described as results of collections
made in southeastern Brazil: Baeus fluminensis new species, B. itatiaiaensis new
species, B. leucophthalmus new species, B. melanocephalus new species and B.
morenus new species. An updated key to the known Neotropical spe- cies of the
genus is also provided.
PMID- 26438925
TI - Prodasineura yulan (Odonata: Zygoptera: Platycnemididae), a new species from
Sarawak.
AB - Prodasineura yulan is described from a male from Maludam National Park, Betong
Division, Sarawak, Malaysian Borneo. It is allied to Prodasineura interrupta.
PMID- 26438926
TI - Ctenus monaghani spec. nov., a nocturnal hunter from the forest floor in Laos
(Araneae: Ctenidae).
PMID- 26438927
TI - A new species of Margotrema (Digenea, Allocreadiidae) from the leopard splitfin
Xenotaenia resolanae (Cyprinodontiformes, Goodeidae) from west-central Mexico.
PMID- 26438928
TI - Ptilopachinae: a new subfamily of the Odontophoridae (Aves: Galliformes).
PMID- 26438929
TI - A nomenclatorial confusion in Tanymastigidae (Crustacea: Branchiopoda:
Anostraca).
PMID- 26438930
TI - Casey's conundrum, a review of the genus Semanotus Mulsant (Coleoptera:
Cerambycidae: Cerambycinae: Callidiini) in North America.
AB - The North American species of Semanotus Mulsant, 1839 are reviewed. Semanotus
ligneus (Fabricius, 1787), Semanotus amplus amplus (Casey, 1912) new status, S.
amplus basalis (Casey, 1924) new status, Semanotus amplus sequoiae Van Dyke, 1923
new status, Semanotus conformis Casey, 1924 new status, Semanotus terminatus
Casey, 1912 new status, Semanotus amethystinus (LeConte, 1853), Semanotus
juniperi (Fisher, 1915), and Semanotus litigiosus (Casey, 1891) are recognized as
valid. A key to the North American fauna, as well as to Semanotus japonicus
Lacordaire, 1869 and Semanotus australis Giesbert, 1993 is included. A
morphometric study was conducted using 37 measured characters from adults of S.
litigiosus. Data were examined using stepwise discriminant analysis to determine
which characters aid in the diagnosis of taxa, and their amounts of resolving
power using canonical variates analysis. Morphometrics revealed significant
sexual dimorphism among taxa and suggested that three taxa were present, however,
only two taxa could be reasonably separated using observable characters.
Phylogenetic analysis using a hypothetical ancestor as out-group returned a
single most parsimonious tree for North American Semanotus.
PMID- 26438931
TI - Description and Ecology of A New Cavernicolous, Arachnophilous Thread- legged Bug
(Hemiptera: Reduviidae: Emesini) from Kartchner Caverns, Cochise County, Arizona.
AB - A new cavernicolous, arachnophilous thread-legged bug (Phasmatocoris
labyrinthicus sp. nov.; Reduviidae: Emesini) is described from Kartchner Caverns,
a limestone cavern in Kartchner Caverns State Park near Benson, Arizona, USA.
Cavernicolous emesines are recorded from caves in many parts of the world and are
distributed across several genera, but are generally uncommon. P. labyrinthicus
shows no obvious troglomorphy but ecological evidence suggests it is, at minimum,
a cave-limited troglophile. The species seems to be low-humidity intolerant, due
to its occurrence in a cave within a desert region, effectively confines the
population to the cave, and the species may thus actually be troglobitic by
default. Arachnophily in emesines is more common, including in Phasmatocoris
Breddin, but has been previously documented in only a single cavernicolous
species, Bagauda cavernicola Paiva, reported from India, Malaysia and Sri Lanka.
However, unlike P. labyrinthicus, B. cavernicola is apparently not
morphologically adapted for its arachnophilous association. P. labyrinthicus is
the only known troglophilic emesine that is also a morphologically adapted and
behaviorally functional arachnophile. The only other known cavernicolous
Phasmatocoris (P. xavieri Gil-Santana, Alves, Barrett and Costa) is recorded from
a sandstone cave in Brazil. P. xavieri exhibits morphological features indicative
of a potentially arachnophilous habit, but its ecology has not been studied.
Adults of P. labyrinthicus share characteristics with the species Phasmatocoris
praecellens Bergroth, P. minor McAtee and Malloch, P. xavieri, P. spectrum
Breddin, and P. rapax McAtee and Malloch. Phasmatocoris is primarily a
Neotropical genus and the discovery of P. labyrinthicus represents a significant
range extension for the genus, being the first Nearctic species identified, with
its geographically nearest relative an undescribed species from Mazatlan, Mexico,
over 1,000 km to the south.
PMID- 26438932
TI - The type specimens of Tachinidae (Diptera) housed in the Museo Argentino de
Ciencias Naturales "Bernardino Rivadavia", Buenos Aires.
AB - The type material of species of Tachinidae (Diptera) housed in the collection of
the Entomology Division of the Museo Argentino de Ciencias Naturales "Bernardino
Rivadavia" were examined and are herein documented. The collection contains 202
type specimens consisting of 54 species described by E.E. Blanchard and 12
described by J. Brethes. Comparison of their original descriptions with the label
information reveals the existence of 24 holotypes, 1 lectotype, 141 syntypes and
36 paratypes. Complete information is given for each type, including reference to
the original description, label data, and preservation condition.
PMID- 26438933
TI - A new barbeled goby from south China (Teleostei: Gobiidae).
AB - A new goby species Tridentiger radiatus sp. nov. is described from Zhuhai,
Guangdong Province of China. The new species, found in sympatry with a widely
distributed barbeled congener Tridentiger barbatus (Gunther, 1861), is one of the
only two Tridentiger species known to possess mandibular and cheek barbels.
Tridentiger radiatus is diagnosed by having higher longitudinal and transverse
scale counts, less developed barbels, unmottled colouration compared to T
barbatus, and 3 dusky radiating infraorbital bands. Partial 12s rDNA sequence
data obtained from 5 individuals of T radiatus and 2 individuals of T. barbatus,
together with published sequence data of other congeners confirmed validity of
the new species. The divergence between T. radiatus and T. barbatus well exceeds
the divergence of other sister taxa in the same genus. Monophyly of the two
barbeled species is supported.
PMID- 26438934
TI - Anserobilharzia gen. n. (Digenea, Schistosomatidae) and redescription of A.
brantae (Farr & Blankemeyer, 1956) comb. n. (syn. Trichobilharzia brantae), a
parasite of geese (Anseriformes).
AB - A new genus, Anserobilharzia, is proposed to accommodate Anserobilharzia brantae
n. comb. (syn. Trichobilharzia bran- tae Farr & Blankemeyer, 1956), a species of
avian schistosome thus far found exclusively in anserini geese (Anser, Branta,
Chen) from Europe and North America, and Gyraulus snails. Recent collections and
subsequent molecular analyses showed that A. brantae was distinct from
Allobilharzia and Trichobilharzia and grouped basal to Trichobilharzia. Using
nuclear 28S, ITS and mitochondrial cox1 as genetic yardsticks, samples of A.
brantae from North America and Europe were each other's closest relative and
distinct from Allobilharzia and Trichobilharzia. Anserobilharzia brantae was also
distinct when compared morphologically with other species of closely related
avian schistosomes. The following descrip- tion is based on males, females, eggs,
and cercariae. The new genus is characterized by a) ovoid egg (72-145um x 44- 89
um) with spine, b) male with > 500 testes and caecal reunion anteriad to seminal
vesicle, c) cercariae with 5+1 flame cells, and d) intermediate hosts are
planorbid snails. The only confirmed species of snail host is Gyraulus parvus in
North America. Based on presented data, we propose a new genus and new
combination for A. brantae justified by morpholog- ical, host use, and molecular
characteristics.
PMID- 26438935
TI - Putative type specimens of Satyrichthys (Scorpaeniformes: Peristediidae) in the
Bleeker collection of the Naturalis Biodiversity Center, Leiden, The Netherlands.
AB - The presumed type status of the two remaining specimens of Peristedion moluccense
Bleeker 1850 in the collection the Naturalis Biodiversity Center was examined by
comparing them to descriptions in two Bleeker papers and an unpublished
manuscript by Bleeker written for the Atlas Ichthyologique. Latin, French and
Dutch parts of these papers were translated into English. The Dutch description
of P. laticeps Schlegel 1852 was also translated. In the course of this study it
became clear why Bleeker considered P. laticeps, a as a synonym of P. moluccense.
PMID- 26438936
TI - A review of Neotropical species in Thienemanniella Kieffer (Diptera,
Chironomidae).
AB - Three species previously described from the neotropical region are revised and
four new species are described: Thienemanniella biobio sp. n. and T. manihuales
sp. n. as males and pupae from Chile, T. sancticaroli sp. n. and T ubatuba sp. n.
as males, females and immature stages from Brazil. The new Thienemanniella spreta
species group is delimited consisting of T. spreta (Roback) sensu Sublette &
Sasa, T. sanctivincenta Saether, T. liae Paggi, T. sancticaroli sp. n. and T.
ubatuba sp. n. Keys to the known Neotropical males, pupae and larvae are
presented.
PMID- 26438937
TI - Complex phylogeography in Rhinoclemmys melanosterna: conflicting mitochondrial
and nuclear evidence suggests past hybridization (Testudines: Geoemydidae).
AB - We examined differentiation within the Colombian wood turtle Rhinoclemmys
melanosterna, and among R. melanosterna and the closely allied species R.
diademata, R.funerea and R. punctularia, based on 1060 base pairs of the
mitochondrial cyt b gene. We also assessed the phylogenetic relationships among
these species using 2050 bp of mtDNA (partial cyt b, 12S and 16S genes) and 3620
bp of nuclear DNA (partial Rag 1, Rag 2, C-mos, R35 and ODC genes). There is
considerable phylogeographic structuring within R. melanosterna, with seven
distinct clades distributed across the species' range. These clades correlate to
some extent with previously described differences in the dorsal pattern of head
coloration. Individual and combined analyses of mitochondrial and nuclear DNA
indicated contradictory relationships among R. melanosterna, R. diademata, R.
funerea and R. punctularia. Mitochondrial DNA sequences revealed R. melanosterna
to be non-monophyletic with respect to R. diademata, R. funerea and R.
punctularia. In contrast, R. melanosterna constituted a well-supported
monophyletic clade using nuclear DNA. This conflict between mitochondrial and
nuclear data suggests past gene flow among the allopatrically and parapatrically
distributed species R. melanosterna, R. diademata, R. funerea and R. punctularia.
Compared to the other Rhinoclemmys species, the taxa under study are weakly
differentiated. To assess their taxonomic status, further research is warranted
using additional nuclear markers and additional samples of R. diademata, R.
funerea and R. punctularia. For the time being, a continued classification of R.
melanosterna, R. diademata, R. funerea and R. punctularia as distinct species is
justified owing to their allopatric and parapatric distributions, and to conserve
the established usage of names that is based on morphological and karyotypic
differentiation.
PMID- 26438938
TI - Redescription of Anomala eucoma Bates, 1888 and a description of three new
species from Costa Rica (Coleoptera: Scarabaeidae: Rutelinae).
AB - Anomala eucoma Bates, 1888 is redescribed and a lectotype from Guatemala is
designated. Three new species from Costa Rica, A. flavacoma new species, A.
megaparamera new species, and A. pseudoeucoma new species, are described, and a
distribution map is given. The internal sac (endophallus) of the species covered
is illustrated, and its use in separating closely related species in this region
is discussed. An identification key for morphologically similar species from the
Neotropical region is provided.
PMID- 26438939
TI - Additional records of the pagurid hermit crab genus Trichopagurus de Saint
Laurent, 1968 (Crustacea: Decapoda: Anomura), with description of a new species
from the Philippines.
AB - The pagurid hermit crab genus Trichopagurus de Saint Laurent, 1968 is currently
represented by three shallow water spe- cies from the tropical Indo-West Pacific
region. In this paper, three species of the genus, including one new species, are
reported. Trichopagurus tenuidactylus n. sp. is described on the basis of a
single ovigerous female from the Bohol Sea, the Philippines, and compared with
two close relatives, T. asper Komai & Poupin, 2012 and T. macrochela Komai & Os-
awa, 2005. New locality records are provided for T. macrochela (the Philippines)
and T. trichophthalinus (Forest, 1954) (Taiwan and Marianas). An identification
key to the four species of the genus is presented.
PMID- 26438940
TI - On hypogean Roncocreagris (Arachnida: Pseudoscorpiones: Neobisiidae) from
Portugal, with descriptions of three new species.
AB - Three new hypogean species of the Iberian genus Roncocreagris Mahnert, 1974 are
described from mainland Portugal: R. borgesi sp. nov. and R. gepesi sp. nov. from
caves in the Sico massif, and R. occidentalis sp. nov. from caves in the
Montejunto and Cesaredas karst plateau. This brings to nine the number of known
hypogean species of the mostly Iberian genus Roncocreagris: five from Portugal
and four from Spain. Ecological comments and new localities for some of the
previously known species are also included.
PMID- 26438941
TI - First records of the genus Hishimonus Ishihara from Thailand (Hemiptera:
Cicadellidae: Deltocephalinae: Opsiini) including description of three new
species.
AB - Seven species of Hishimonus Ishihara are recorded in Thailand, four of which were
previously recorded from neighbouring countries and three new species described
herein: Hishimonus pallidus sp. nov., H. diffractus sp. nov. and H. gillespiei
sp. nov. The other four species are H. concavus Knight, previously known from the
Philippines, H. subtilis Knight recorded from Singapore, H. aberrans Knight
recorded from Taiwan and H. phycitis (Distant), which is widespread in Asia from
the Middle East to China. These species are all newly recorded from Thailand and
represent the first records of the genus Hishimonus in that country.
PMID- 26438942
TI - A new species of the putatively myrmecophilous genus Plaumanniola Costa Lima,
with notes on the systematic position of Plaumanniolini (Coleoptera:
Staphylinidae: Scydmaeninae).
AB - The enigmatic Neotropical genus Plaumanniola Costa Lima is revised. Plaumanniola
sanctaecatharinae is redescribed and P. regina sp. n. is described (both from
Brazil). Morphological structures of Plaumanniola are illustrated and the
systematic position of the tribe Plaumanniolini is discussed. A previously
postulated myrmecophily of this morphologically highly unusual genus is found to
be weakly supported by biological observations and should be treated as a
supposition that needs further study.
PMID- 26438943
TI - A new subtidal species of the genus Petrolisthes Stimpson, 1858 (Crustacea:
Decapoda: Porcellanidae) from Okinawa, with an account of species of the genus
known from the Ryukyu Islands, southwestern Japan.
AB - A new porcellanid crab, Petrolisthes uruma sp. nov., is described based on a
single specimen collected from Okinawajima Island in the Ryukyus, southwestern
Japan. The unique holotype was collected from a subtidal depth of 10 m, though
vast majority of the genus occur in intertidal to shallow subtidal zone. The new
species is morphologically closest to P. noluccensis (De Man, 1888), but is
distinguished by the weaker striation on the carapace, the proportionally longer
carpus of the cheliped, the number of the anterior marginal teeth of the carpus
of the cheliped, and the meri of the second and third pereopods each with a much
stronger spine at the lateroventral distal angle. A brief note on species of
Petrolisthes presently known from the Ryukyu Islands is given.
PMID- 26438944
TI - Fissarcturus walteri sp. nov. from the Ross Sea of the Southern Ocean (Isopoda,
Antarcturidae).
AB - During the Victoria-Land Transect project two specimens of a new species,
Fissarcturus walteri sp. nov., were found in the Ross Sea along the Victoria Land
Coast, Antarctica, during the 19th Italica expedition in February 2004. This is
the second species of Fissarcturus from the Ross Sea after F. rossi Brandt, 2007.
F. walteri sp. nov. is most similar to Fissarcturus granulosus (Nordenstam, 1933)
from South Georgia but can be distinguished by the blunt short, anteriorly
directed supraocular spines and elevations and some other characters as described
herewith.
PMID- 26438945
TI - A new fairy shrimp Phallocryptus tserensodnomi (Branchiopoda: Anostraca) from
Mongolia.
AB - A new species of Phallocryptus Biraben 1951 (Branchiopoda, Anostraca) from
Mongolia is described. Phallocryptus tserensodnomi sp. nov. is close to P.
spinosa (Milne-Edwards 1840), but both morphological and molecular analyses
(Cytochrome Oxidase I, COI) indicate that they represent separate species. Most
relevant differential features of the new species include: (1) frontal appendage
provided with small ventral conical outgrowths; (2) second antennamere evenly
curved, sickle-shaped; (3) distal fleshy process on labrum evenly curved forwards
and tapering; (4) short stout acute spine-like projections present at each side
of basal portion of gonopods; (5) female second antennae shorter and wider than
in P. spinosa, tapering. Based on morphological comparisons the new species
appears to be a Mongolian endemic, although some genotypes of presumed P spinosa
from Africa are similar to the new species, suggesting P. tserensodnomi might
have a wider distribution.
PMID- 26438947
TI - Taxonomic notes and description of the male of Xenochlora nigrofemorata (Smith,
1879) (Hymenoptera: Apidae: Halictinae).
AB - The present work describes for the first time the male of the bee genus
Xenochlora Engel, Brooks & Yanega, 1997. The male of X. nigrofemorata (Smith,
1879) is described and illustrated. Additionally, Megalopta opacicollis Friese,
1926 is placed as a junior synonym of X. nigrofemorata (Smith, 1879).
PMID- 26438946
TI - A new leafhopper genus and two new species of the tribe Scaphytopiini (Hemiptera:
Cicadellidae: Deltocephalinae) from China.
AB - New leafhopper taxa in the deltocephaline tribe Scaphytopiini Oman are described:
Xenovarta lui sp. n., and a new genus and species Aparaphysis lushuiiensis, gen.
n., sp. n. from China. Detailed morphological descriptions and illustrations of
the new genus and species are given. A checklist to genera of Scaphytopiini is
provided.
PMID- 26438948
TI - New Phlugidia species (Orthoptera: Tettigoniidae: Meconematinae, Phlugidini) from
the Eastern Arc Mountains of Tanzania, Africa.
AB - Two new species of Phlugidia (Orthoptera: Tettigoniidae: Meconematinae) are
described from the Eastern Arc Mountains of Tanzania. P. planicercus Hemp n. sp.
occurs in lowland forest at the foothills of the Uluguru Mountains, while P. ob-
tusicercus Hemp n. sp. was collected in the Nguru Mountains. A key to Phlugidia
species is provided.
PMID- 26438949
TI - Two new quill mite species (Prostigmata: Syringophilidae) parasitizing Australian
birds.
AB - Two new quill mite species (Prostigmata: Cheyletoidea: Syringophilidae),
Syringophilopsis philemonis sp. nov. from Philemon citreogularis (Gould)
(Passeriformes: Meliphagidae) and Megasyringophilus cacatua sp. nov. from Cacatua
galerita (Latham) (Psittaciformes: Psittacidae) are described from Australia.
PMID- 26438950
TI - First Report of Sabella spallanzanii (Gmelin, 1791) (Annelida: Polychaeta) from
Botany Bay, New South Wales, a northern range extension for the invasive species
within Australia.
PMID- 26438951
TI - The tadpole of the Melville Range Treefrog Litoria andiirrmalin (Anura: Hylidae).
PMID- 26438952
TI - Nomenclatural changes for the genus name Perinetia, with a new replacement name
for Perinetia Barnard, 1959 (Crustacea: Isopoda: Oniscidea: Philosciidae).
PMID- 26438953
TI - Taxonomy and redescription of the Atherton Antechinus, Antechinus godmani
(Thomas) (Marsupialia: Dasyuridae).
AB - We provide a taxonomic redescription of the dasyurid marsupial Atherton
Antechinus, Antechinus godmani (Thomas). A. godmani is only rarely encountered
and limited to wet tropical rainforests of north-east Queensland, Australia,
between the towns of Cardwell and Cairns (a distribution spanning 135 kilometres
from north to south). The distinctive species occurs at altitudes of over 600
meters asl, in all major rainforest types, and can be found with both the
northern subspecies of the Yellow-footed Antechinus, A. flavipes rubeculus Van
Dyck and the Rusty Antechinus, A. adustus (Thomas). A. godmani is clearly
separated from all congeners on the basis of both morphometrics and genetics. A.
godmani can be distinguished from all extant congeners based on external
morphology by a combination of large size, naked-looking tail and reddish fur on
the face and head. A. godmani skulls are characteristically large, with a suite
of long features: basicranium, palate, upper premolar tooth row, inter-palatal
vacuity distance and dentary. Phylogenies generated from mt- and nDNA data
position Antechinus godmani as monophyletic with respect to other members of the
genus; A. godmani is strongly supported as the sister-group to a clade containing
all other antechinus, but excluding the south-east Australian Dusky Antechinus,
A. swainsonii (Waterhouse) and Swamp Antechinus, A. minimus (Geoffroy).
Antechinus godmani are genetically very divergent compared to all congeners
(mtDNA: range 12.9-16.3%).
PMID- 26438954
TI - Review of the earthworm fauna of Iran with emphasis on Kohgiluyeh & Boyer-Ahmad
Province.
AB - Earthworms were collected in forests, damp habitats, springs, orchards and
agricultural fields of the Kohgiluyeh & Boyer Ahmad Province, Iran, from April
2009 to April 2010. Specimens were collected at 20 established stations by
digging and by diluted formalin methods. Ten species belonging to family
Lumbricidae were identified based on morphology: Aporrectodea caliginosa
(Savigny, 1826), Ap. rosea (Savigny, 1826), Ap. jassyensis (Michaelsen, 1891),
Dendrobaena veneta (Rosa, 1886), D. byblica (Rosa, 1893) complex, D. orientalis
orientalis Cernosvitov 1940, Eisenia fetida (Savigny, 1826), Eiseniella tetraedra
(Savigny, 1826), Octolasion lacteum (Orley, 1881), Perelia kaznakovi (Michaelsen,
1910). Ap. caliginosa was the dominant species in this province and D. orientalis
orientalis is a new record for Iran. A checklist of all earthworms species form
Iran is presented, containing 19 species. Then, in order to show earthworm
geographical affinities, hierarchical analysis were applied to available data on
earthworm of Iran.
PMID- 26438955
TI - Five new minute orb-weaving spiders of the family Mysmenidae from China
(Araneae).
AB - Five new mysmenid species are described from Southwest China including Mosu dayan
n. sp. (male and female), Mosu tanjia n. sp. (male and female), Mysmena
baoxingensis n. sp. (male and female), Mysimenella yinae n. sp. (male and
female), Trogloneta uncata n. sp. (male). Males of the genus Mosu are described
for the first time. All new species are from caves or leaf litter. Morphological
illustrations and photos of all new species are given.
PMID- 26438956
TI - Three new species of Oppioidea (Acari: Oribatida) from India.
AB - Three new oribatid mite species of the superfamily Oppioidea--Cycloppia asetosa
sp. nov., C. spindleformis sp. nov. and Hammerella (Hammerella) excisa sp. nov.-
are described from India. The genus Cycloppia and subgenus Hammerella
(Hammerella) are for the first time recorded in India. Cycloppia asetosa sp. nov.
differs from all species of Cycloppia by the rostrum with indentation and the
absence of interlamellar setae and their alveoli. Cycloppia spindleformis sp.
nov. dif- fers from all species of Cycloppia by the presence of interlamellar
alveoli only. Hammerella (H.) excisa sp. nov. differs from all species of
Hammerella (Hammerella) by the rostrum with indentation and the presence of
notogastral setae c. The identification keys to all known species of Cycloppia
and Hammerella (Hammerella) are provided.
PMID- 26438957
TI - Revision of the species of the bee genus Caenohalictus (Hymenoptera: Halictidae)
occurring in Argentinean Patagonia.
AB - The species of the halictid bee genus Caenohalictus Cameron occurring in
Argentinean Patagonia are revised. Eight species are recognized, one of them here
described as new: Caenohalictus flammeus n. sp. The female of C. turquesa Rojas &
Toro 2000 is described for the first time. Pseudagapostemon babuarus Jorgensen
1912, based on the male holotype, is synonymized under Augochlora
(Pseudaugochloropsis) thamyris Jorgensen 1912, based on the female lectotype.
Lectotypes are designated for Augochlora (Pseudaugochloropsis) thamyris Jorgensen
1912 and Halictomorpha autumnalis Jorgensen 1912. Caenohalictus cyanopygus Rojas
& Toro 2000, C. galletue Rojas & Toro 2000, C. iodurus (Vachal 1903), C.
opaciceps (Friese 1916), and C. turquesa Rojas & Toro 2000, all known from Chile,
are cited for Argentina for the first time. Notes on the variation observed
within species, images of diagnostic structures, a key to the species and
distributional data are provided. In addition, DNA barcoding results for four
species are briefly discussed.
PMID- 26438958
TI - Aphyosemion pamaense, a new killifish species (Cyprinodontiformes:
Nothobranchiidae) from Cameroon.
AB - Aphyosemion panaense sp. nov. is described from the Pama River, a small tributary
of the Nyong, in the surroundings of Pama, Cameroon. It belongs to the subgenus
Chromaphyosenion Radda, 1971 and is distinguished from its relatives by a
unique/diagnostic combination of characters: orange unpaired fins, an anal fin
without spots, an orange throat and purple to blue-grey flanks. The new species
is also genetically differentiated from all the other Chromaphyosemion species as
revealed by mtDNA (cytochrome b) analysis and characterised by a unique karyotype
showing tentative sex chromosomes with 2n=35 chromosomes in males versus 2n=36 in
females.
PMID- 26438959
TI - New species of Aleurodamaeus Grandjean, 1954 (Oribatida: Aleurodamaeidae) from
South Africa.
AB - Seven new species of Aleurodamaeus (Oribatida: Aleurodamaeidae) from South Africa
are described: A. salvadordalii sp. nov., A. vicinus sp. nov., A. angelae sp.
nov., A. niedbalai sp. nov., A. minutus sp. nov., A. woasi sp. nov. and A.
prominens sp. nov. Their distribution in South Africa is discussed. Aleurodamaeus
deswardti (Hugo, 2010) comb. nov. is proposed. A key to all South African species
of Aleurodamaeus is provided.
PMID- 26438960
TI - Oribatid mite fossils from pre-Quaternary sediments in Slovenian caves II.
Amiracarus pliocennatus n.gen., n.sp. (Microzetidae) from Pliocene, with comments
on the other species of the genus.
AB - Amiracarus pliocennatus n. gen., n. sp. is described based on fossils found in
Pliocene and Pleistocene clastic sediments in caves of the Slovenian Classical
Karst (Kras). Diagnosis and relationships of the new genus are given and
relationships within the extant species of the genus are discussed as well as
variability and reliability of some characters, used for species differentiation.
Amiracarus senensis (Bernini 1975) n. comb. is proposed as a type species of the
new genus, and other four extant species are newly placed in Amiracarus n. gen.:
A. abeloosi (Lions 1978) n. comb., A. discrepans (Mahunka 1966) n. comb., A.
grootaerti (Wauthy &Ducarme 2011) n. comb. and A. similis (Subias &
Iturrondobeitia 1978) n. comb. Finding of a fossil individual of M. senensis
Bernini 1975 in Ponicova Cave of South-West Carpathians in Romania is reported
and a description of this individual is given. Relationships with the genus
Miracarus Kunst 1959 are discussed and a new diagnosis of this genus is also
given, along with the redescription of its type species, M. hurkai Kunst 1959.
PMID- 26438961
TI - Description of a new species of Microhyla from Bali, Indonesia (Amphibia, Anura).
AB - We describe a microhylid frog from Bali, Indonesia as a new species, Microhyla
orientalis sp. nov. It belongs to the M. achatina group and is close to M.
mantheyi, M. malang, and M. borneensis. It is distinguished from its congeners by
a combination of the following characters: small size (adult males about 16-17 mm
in SVL); a faint vertebral stripe present; a black lateral stripe from behind eye
to half length of trunk; snout rounded in profile; eyelid without supraciliary
spines; first finger less than one-fifth of third; tips of three outer fingers
weakly dilated, forming weak disks, dorsally with median longitudinal groove;
outer palmar tubercle single; tibiotarsal articulation reaching up to center of
eye; tips of toes distinctly dilated into disks, dorsally with median
longitudinal groove; inner and outer metatarsal tubercles present; four or more
phalanges on inner and outer sides of fourth toe, and three phalanges on inner
side of fifth toe free of web; and tail of larva with a black marking at middle.
The male advertisement call of the new species consists of a series of notes each
lasts for 0.01-0.08 s and composed of 3-5 pulses with a dominant frequency of 3.2
3.6 kHz. Uncorrected sequence divergences between M. orientalis and all
homologous 16S rRNA sequences available were > 6.6%. At present, the new species
is known from rice fields between 435-815 m elevation in Wongaya Gede and
Batukaru.
PMID- 26438962
TI - Two new species of Halacarus (Acari, Prostigmata) from Brazil.
AB - The genus Halacarus is recorded from the Brazilian littoral for the first time.
Two new species are described. Halacarus omului sp. nov., obtained from algae on
the intertidal or immediate subtidal, is a member of the actenos species group
and can be distinguished from most congeners by having fifth and sixth pairs of
dorsal setae immediately adjacent to fourth and fifth pairs of gland pores, on
same minute sclerite. Halacarus todaroi sp. nov. was obtained from sublittoral
coarse sand and shell debris and can be distinguished from most congeners by
lacking sexually dimorphic dorsal plates, the presence of the posterior dorsal
plate, although it does not bear the fourth pair of gland pores, and the presence
of ocular plates as a small platelet bearing the pore canaliculi. Further
diagnoses are provided along with the species descriptions.
PMID- 26438963
TI - Metabolomics-Driven Discovery of a Prenylated Isatin Antibiotic Produced by
Streptomyces Species MBT28.
AB - Actinomycetes are a major source of antimicrobials, anticancer compounds, and
other medically important products, and their genomes harbor extensive
biosynthetic potential. Major challenges in the screening of these microorganisms
are to activate the expression of cryptic biosynthetic gene clusters and the
development of technologies for efficient dereplication of known molecules. Here
we report the identification of a previously unidentified isatin-type antibiotic
produced by Streptomyces sp. MBT28, following a strategy based on NMR-based
metabolomics combined with the introduction of streptomycin resistance in the
producer strain. NMR-guided isolation by tracking the target proton signal
resulted in the characterization of 7-prenylisatin (1) with antimicrobial
activity against Bacillus subtilis. The metabolite-guided genome mining of
Streptomyces sp. MBT28 combined with proteomics identified a gene cluster with an
indole prenyltransferase that catalyzes the conversion of tryptophan into 7
prenylisatin. This study underlines the applicability of NMR-based metabolomics
in facilitating the discovery of novel antibiotics.
PMID- 26438964
TI - Fast, Ultrasensitive Detection of Reactive Oxygen Species Using a Carbon Nanotube
Based-Electrocatalytic Intracellular Sensor.
AB - Herein, we report a highly sensitive electrocatalytic sensor-cell construct that
can electrochemically communicate with the internal environment of immune cells
(e.g., macrophages) via the selective monitoring of a particular reactive oxygen
species (ROS), hydrogen peroxide. The sensor, which is based on vertically
aligned single-walled carbon nanotubes functionalized with an osmium
electrocatalyst, enabled the unprecedented detection of a local intracellular
"pulse" of ROS on a short second time scale in response to bacterial endotoxin
(lipopolysaccharide-LPS) stimulation. Our studies have shown that this initial
pulse of ROS is dependent on NADPH oxidase (NOX) and toll like receptor 4 (TLR4).
The results suggest that bacteria can induce a rapid intracellular pulse of ROS
in macrophages that initiates the classical innate immune response of these cells
to infection.
PMID- 26438968
TI - Predictors of health of pre-registration nursing and midwifery students: Findings
from a cross-sectional survey.
AB - BACKGROUND: Student nurses/midwives evidence less than exemplary lifestyle habits
and poor emotional health, despite exposure to health education/promotion during
their educational preparation. Knowledge of the factors that predict
nursing/midwifery students' health could inform strategies to enhance their
health and increase their credibility as future health promoters/educators.
OBJECTIVE: To establish the predictors of nursing/midwifery student emotional
health. DESIGN: Cross-sectional survey. SETTING: The research took place at a
university in Ireland. PARTICIPANTS: We involved a total sample (n=473) student
nurses/midwives. METHODS: Participants completed the General Health
Questionnaire, Lifestyle Behaviour Questionnaire and Ways of Coping Questionnaire
to determine their self-reported emotional health, lifestyle behaviour and coping
processes. Multivariate regression was performed to identify the predictors of
student emotional health (dependent variable). The independent variables were
demographics, coping, lifestyle behaviour and students' perceptions of
determinants of their health. RESULTS: Many respondents reported significant
emotional distress (48.71%) and unhealthy lifestyle behaviours including smoking
(27.94%), physical inactivity (34.29%), alcohol consumption (91.7%) and unhealthy
diet (28.05%). Multivariate regressions indicated that the predictors of
emotional distress included gender, year of study, smoking, passive coping and
beliefs that their student life was stressful or/and that worry stress and
boredom adversely impacted their diet. CONCLUSIONS: Targeting student's beliefs
regarding influences upon their health, promotion of positive lifestyles and
adaptive coping is necessary to facilitate health gain of future health
professionals.
PMID- 26438970
TI - Letter from the President of the Argentinian Society of Pharmacology.
PMID- 26438969
TI - Assessing the efficacy of melatonin to curtail benzodiazepine/Z drug abuse.
AB - The abuse of benzodiazepine (BZP) and Z drugs has become, due to the tolerance
and dependence they produce, a serious public health problem. Thirty years ago,
we demonstrated in experimental animals the interaction of melatonin with central
BZD receptors, and in 1997 we published the first series of elderly patients who
reduced BZP consumption after melatonin treatment. Almost every single neuron in
the hypothalamic suprachiasmatic nuclei (SCN), the central pacemaker of the
circadian system, contains gamma-aminobutyric acid (GABA) and many results in
animals point out to a melatonin interaction with GABA-containing neurons. In
addition, central-type BZD antagonism, that obliterates GABAA receptor function,
blunted most behavioral effects of melatonin including sleep. Melatonin is
involved in the regulation of human sleep. This is supported by the temporal
relationship between the rise of plasma melatonin levels and sleep propensity as
well as by the sleep-promoting effects of exogenously administered melatonin.
Both meta-analyses and consensus agreements give support to the therapeutic use
of melatonin in sleep disorders. This action is attributed to MT1 and MT2
melatoninergic receptors localized in the SCN, as well as in other brain areas.
This review discusses available data on the efficacy of melatonin to curtail
chronic BZD/Z drug use in insomnia patients. A major advantage is that melatonin
has a very safe profile, it is usually remarkably well tolerated and, in some
studies, it has been administered to patients at very large doses and for long
periods of time, without any potentiality of abuse. Further studies on this
application of melatonin are warranted.
PMID- 26438971
TI - Co-targeting cancer drug escape pathways confers clinical advantage for multi
target anticancer drugs.
AB - Recent investigations have suggested that anticancer therapeutics may be enhanced
by co-targeting the primary anticancer target and the corresponding drug escape
pathways. Whether this strategy confers statistically significant clinical
advantage has not been systematically investigated. This question was probed by
the evaluation of the clinical status and the multiple targets of 23 approved and
136 clinical trial multi-target anticancer drugs with particular focus on those
co-targeting EGFR, HER2, Abl, VEGFR2, mTOR, PI3K, Alk, MEK, KIT, and DNA
topoisomerase, and some of the 14, 7, 13, 20, 6, 5, 7, 2, 4 and 10 cancer drug
escape pathways respectively. Most of the approved (73.9%) and phase III (75.0%),
the majority of the Phase II (62.8%) and I (53.6%), and the minority of the
discontinued (35.3%) multi-target drugs were found to co-target cancer drug
escape pathways. This suggests that co-targeting anticancer targets and drug
escape pathways confer significant clinical advantage and such strategy can be
more extensively explored.
PMID- 26438972
TI - MRI-guided single fraction ablative radiotherapy for early-stage breast cancer: a
brachytherapy versus volumetric modulated arc therapy dosimetry study.
AB - BACKGROUND AND PURPOSE: A radiosurgical treatment approach for early-stage breast
cancer has the potential to minimize the patient's treatment burden. The
dosimetric feasibility for single fraction ablative radiotherapy was evaluated by
comparing volumetric modulated arc therapy (VMAT) with an interstitial
multicatheter brachytherapy (IMB) approach. METHODS AND MATERIALS: The tumors of
20 patients with early-stage breast cancer were delineated on a preoperative
contrast-enhanced planning CT-scan, co-registered with a contrast-enhanced
magnetic resonance imaging (MRI), both in radiotherapy supine position. A dose of
15 Gy was prescribed to the planned target volume of the clinical target volume
(PTVCTV), and 20 Gy integrated boost to the PTV of the gross tumor volume
(PTVGTV). Treatment plans for IMB and VMAT were optimized for adequate target
volume coverage and minimal organs at risk (OAR) dose. RESULTS: The median
PTVGTV/CTV receiving at least 95% of the prescribed dose was ?99% with both
techniques. The median PTVCTV unintentionally receiving 95% of the prescribed
PTVGTV dose was 65.4% and 4.3% with IMB and VMAT, respectively. OAR doses were
comparable with both techniques. CONCLUSION: MRI-guided single fraction
radiotherapy with an integrated ablative boost to the GTV is dosimetrically
feasible with both techniques. We perceive IMB less suitable for clinical
implementation due to PTVCTV overdosage. Future studies have to confirm the
clinical feasibility of the single fraction ablative approach.
PMID- 26438973
TI - Growth and development after oesophageal atresia surgery: Need for long-term
multidisciplinary follow-up.
AB - Survival rates in oesophageal atresia patients have reached over 90%. In long
term follow-up studies the focus has shifted from purely surgical or
gastrointestinal evaluation to a multidisciplinary approach. We reviewed the
literature on the long-term morbidity of these patients and discuss mainly issues
of physical growth and neurodevelopment. We conclude that growth problems - both
stunting and wasting - are frequently seen, but that sufficient longitudinal data
are lacking. Therefore, it is unclear whether catch-up growth into adolescence
and adulthood occurs. Data on determinants of growth retardation are also lacking
in current literature. Studies on neurodevelopment beyond preschool age are
scarce but oesophageal atresia patients seem at risk for academic problems and
motor function delay. Many factors contribute to the susceptibility to growth and
development problems and we propose a multidisciplinary follow-up schedule into
adulthood future care which may help improve quality of life.
PMID- 26438974
TI - Predictors of Survival in Hepatocellular Carcinoma Patients.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common tumor
worldwide, with an incidence equal to the death rate. MATERIAL AND METHODS: We
aimed to detect the prognostic factors for HCC patients. We retrospectively
analyzed 12 years data of 115 patients who have biopsy-proven HCC. Clinical and
demographic characteristics of patients with treatment modalities, survival
rates, and prognostic factors were analyzed. RESULTS: There were 93 male
patients, and the mean age was 63.5+/-11.8 years. Most patients had cirrhosis due
to hepatitis virus infection. Median follow-up time was 17 months (1 month-9.5
years) after the diagnosis of HCC. The nodule was single in 43 (37.4%) patients,
there were 2-3 nodules in 30 (26.1%), and >3 or diffuse nodules in 42 (36.5%)
patients. Distribution of treatment modalities was as follows: 23 (20%) patients
had liver transplantation, 15 (13%) had HCC resection, 12 patients (10.4%) had
radiofrequency ablation (RFA), 26 patients (22.6%) had transarterial
chemoembolization (TACE), 2 (1.7%) had alcohol ablation, and 37 patients (32.2%)
had no treatment. Tumor sizes of 9 patients (39.1%) in the transplanted group
exceeded the Milan criteria. Mean survival was 72+/-6.9, 78.8 +/-12.5, 19.5+/
2.8, 20.6+/-4.2, 16.0+/-5.9 months in those that received transplantation,
resection, RFA, TACE, and no treatment, respectively (p<0.001). Survival was
significantly poorer in patients >63 years old (p=0.001), with serum albumin
level <=3.4 g/dL (p=0.01), and with diffuse HCC (p<0.001). CONCLUSIONS: Survival
was significantly better in patients who underwent liver transplantation or
surgical resection. Tumor number, age, and serum albumin level were the most
important prognostic factors related to overall survival.
PMID- 26438975
TI - Persistence and variation in microstructural design during the evolution of
spider silk.
AB - The extraordinary mechanical performance of spider dragline silk is explained by
its highly ordered microstructure and results from the sequences of its
constituent proteins. This optimized microstructural organization simultaneously
achieves high tensile strength and strain at breaking by taking advantage of weak
molecular interactions. However, elucidating how the original design evolved over
the 400 million year history of spider silk, and identifying the basic
relationships between microstructural details and performance have proven
difficult tasks. Here we show that the analysis of maximum supercontracted single
spider silk fibers using X ray diffraction shows a complex picture of silk
evolution where some key microstructural features are conserved phylogenetically
while others show substantial variation even among closely related species. This
new understanding helps elucidate which microstructural features need to be
copied in order to produce the next generation of biomimetic silk fibers.
PMID- 26438976
TI - Vertical eruption patterns of impacted mandibular third molars after the
mesialization of second molars using miniscrews.
AB - OBJECTIVE: To investigate (1) whether vertical eruption of impacted third molars
improves after mesialization of second molars and (2) what factors affect the
vertical eruption of impacted third molars when space caused by missing molars is
successfully closed by mesialization of the second molar using miniscrews.
MATERIALS AND METHODS: The treatment group (Group 1) included 52 patients who had
(1) missing mandibular first molars (ML-6) or missing deciduous mandibular second
molars (ML-E), (2) initially impacted mandibular third molars, and (3) successful
space closure of the edentulous area with orthodontics. Panoramic radiographs at
start of treatment (T1) and at time of space closure (T2) were collected. The
control group (Group 2) included 46 nonedentulous patients with impacted
mandibular third molars without molar protraction treatment. Panoramic
radiographs with similar T1/T2 treatment times were selected. Nine measurements
were obtained regarding horizontal available space, vertical eruption, and third
molar angulation. RESULTS: Third molars erupted vertically an average of 2.54 mm
in Group 1 compared with 0.41 mm in Group 2. Age, gender, Nolla stage, and angle
of the third molars did not show significant correlations with the vertical
change of the impacted third molars, whereas the depth of third molar impaction
and available space showed significant correlations. CONCLUSIONS: Impacted
mandibular third molars vertically erupt as a result of uprighting with
mesialization of the second molar, and vertical eruption is affected by the
initial vertical location of impacted third molars and available space.
PMID- 26438977
TI - Conformation-Dependent Photostability among and within Single Conjugated
Polymers.
AB - The relationship between photostability and conformation of 2-methoxy-5-(2'
ethylhexyloxy)-1,4-phenylenevinylene (MEH-PPV) conjugated polymers was studied
via excitation polarization modulation depth (M) measurements. Upon partial
photobleaching, M distributions of collapsed, highly ordered MEH-PPV molecules
shifted toward lower values. Conversely, M distributions of MEH-PPV molecules
with random coil conformations moved toward higher values after partial
photobleaching. Monte Carlo simulations of randomly distributed dipole moments
along polymer chains subjected to partial photobleaching revealed that a
statistical effect leads to an increase in peak M value. Decreases in M values
seen experimentally in the population of MEH-PPV molecules with high M values,
however, are due to conformation-dependent photostability within single MEH-PPV
polymers. We show that, while folded MEH-PPV molecules are relatively more
photostable than extended MEH-PPV molecules in an ensemble, extended portions of
particular molecules are more photostable than folded domains within single MEH
PPV molecules.
PMID- 26438978
TI - ACC/AHA/STS Statement on the Future of Registries and the Performance Measurement
Enterprise: A Report of the American College of Cardiology/American Heart
Association Task Force on Performance Measures and The Society of Thoracic
Surgeons.
PMID- 26438979
TI - Reference range for the pulsatility index ductus venosus Doppler measurement
between 11 and 13 + 6 weeks of gestation in a Brazilian population.
AB - OBJECTIVE: To establish reference range for the pulsatility index (PI) ductus
venosus (DV) Doppler measurement between 11 and 13 + 6 weeks of gestation in a
Brazilian population. METHODS: A retrospective cross-sectional study was
performed with 430 singleton pregnancies. The PI DV Doppler measurement was
performed as routine during the first trimester screening. DV was identified by
color Doppler and the pulsed Doppler gate was placed in the distal portion of the
umbilical sinus. When at least three typical DV waveforms were obtained, PI DV
was measured manually in one waveform. Polynomial regression was used to obtain
the best fit using PI DV Doppler measurement and crown-rump length (CRL) with
adjustments by the determination coefficient (R(2)). 5th, 50th and 95th
percentiles for the PI DV Doppler measurements at each gestational were
determined. RESULTS: The mean of PI DV Doppler measurement was 1.1 +/- 0.2 (range
0.8-3.7). The linear regression was the best fit: PI DV measurement = 1.288
0.0034*CRL (R(2 )= 0.03). CONCLUSIONS: Reference range for the PI DV Doppler
measurement between 11 and 13 + 6 weeks of gestation in a Brazilian population
was established.
PMID- 26438980
TI - Bioactive-glass in periodontal surgery and implant dentistry.
AB - Bioactive-glass (B-G) is a material known for its favorable biological response
when in contact with surrounding fibro-osseous tissues, due not only to an
osteoconductive property, but also to an osteostimulatory capacity, and superior
biocompatibility for use in human body. The objectives of this paper are to
review recent studies on B-G in periodontal and implant therapy, describing its
basic properties and mechanism of activity as well as discoursing about state of
art and future perspective of utilization. From a demonstrated clinical benefit
as bone graft for the elimination of osseous defects due to periodontal disease
(intrabony/furcation defects) and surgeries (alveolar ridge preservation,
maxillary sinus augmentation), to a potential use for manufacturing bioactive
dental implants, possibly allowing wider case selection criteria together with
improved integration rates even in the more challenging osteoporotic and
medically compromised patients, this biomaterial represents an important field of
study with high academic, clinical and industrial importance.
PMID- 26438981
TI - The influence of surface roughness and surface dynamics on the attachment of
Methicillin-Resistant Staphylococcus aureus onto orthodontic retainer materials.
AB - Staphylococci species have been isolated from removable orthodontic retainers.
The aims of this study were to determine the most suitable device to analyze
surface roughness of autopolymerized acrylic and thermoplastic materials and
whether the surface dynamics of these materials influences the attachment of
Methicillin-Resistant Staphylococcus aureus (MRSA). Clinically simulated samples
of autopolymerized acrylic and thermoplastic material were first evaluated using
laser non-contact, stylus mechanical profilometries and atomic force microscopy
(AFM) followed by contact angle measurement to characterize their surface
dynamics. Finally, an in vitro biofilm assay was carried out using a constant
depth film fermentor to assess biofilm attachment. The results showed a
significant difference between the roughness values obtained from the tested
profilometers with the AFM exhibiting the most consistent roughness values. MRSA
tended to accumulate initially within the microscopic irregularities of
autopolymerized acrylic samples whereas acid-base and electron donor interactions
influenced the bacterial attachment onto the thermoplastic samples.
PMID- 26438983
TI - The effect of staining and vacuum sintering on optical and mechanical properties
of partially and fully stabilized monolithic zirconia.
AB - The effect of staining and vacuum sintering on optical properties and the bi
axial flexural strength of partially and fully stabilized monolithic zirconia
(PSZ, FSZ) were evaluated. Disc-shaped specimens divided into three subgroups
(n=15): non-stained, stained and non-stained with vacuum sintering. After
staining and sintering, optical properties were evaluated using a reflection
spectrophotometer and bi-axial flexural strength was tested using the piston-on
three balls technique. Statistical analysis was performed using multivariate
analysis of variance (MANOVA) followed by post-hoc Tukey's tests (p<0.05).
Staining decreased translucency parameter (TP) values of FSZ (p<0.05). Sintering
under vacuum enhanced TP values for PSZ (p<0.05). Staining enhanced surface gloss
for both types of zirconia (p<0.05). Staining increased bi-axial flexural
strength of FSZ (p<0.05), while it decreased the strength of PSZ (p<0.05).
Sintering under vacuum provided minimal benefits with either type of zirconia.
PMID- 26438982
TI - Impact of surface treatment of different reinforced glass-ceramic anterior crowns
on load bearing capacity.
AB - This study investigated the influence of different surface treatments on fracture
load (FL) of canine crowns fabricated from two different pressable lithium
disilicate ceramics: A (HS10PC, estetic ceram, n=180) and B (IPS e.max Press,
IvoclarVivadent, n=120). The standardized specimens were divided into groups of
six different surface treatments and two glazing temperatures. A-group specimens
were additionally assigned two glazing pastes with various thermal expansion
coefficients (TEC). FL was measured and TECs were determined. Data were analyzed
using three/one-way ANOVA followed by post-hoc Scheffe's test. B showed
comparable or higher FL than A (B: 503-876 N; A: 375-734 N). Lithium-disilicate
crowns show higher FL when not grinded but only polished or glazed. Glazing
pastes affected FL depending on their TECs, firing temperature and crown
treatment. TEC of A and B was 10 ppm/K, glazing pastes for A presented TECs of
7.5 ppm/K and 10 ppm/K and for B of 9 ppm/K.
PMID- 26438984
TI - Influence of light intensity on surface-free energy and dentin bond strength of
single-step self-etch adhesives.
AB - In this study, we investigated the influence of light intensity on the surface
free energy and dentin bond strength of single-step selfetch adhesives. The
adhesives were applied to the dentin surfaces of bovine mandibular incisors and
cured with light intensities of 0 (no irradiation), 200, 400, and 600 mW/cm(2).
Surface-free energies were determined by measuring the contact angles of three
test liquids placed on the cured adhesives. Dentin bond strengths of the
specimens were also measured. Polymerization with a higher light intensity
resulted in a lower surface-free energy of the cured adhesives. The greatest bond
strength was achieved when a light intensity of 400 mW/cm(2) or greater was used.
Our data suggest that the surface-free energy and dentin bond strength of single
step self-etch adhesives are affected by light intensity of the curing unit.
PMID- 26438985
TI - Effect of novel restoration techniques on the fracture resistance of teeth
treated endodontically: An in vitro study.
AB - The aim was to evaluate the effects of fiber-reinforced composite restorations
and a bulk-fill resin composite on the fracture strength of mandibular premolars
treated endodontically. Standard mesio-occluso-distal (MOD) cavities were
prepared in 48 mandibular premolars. Following root canal treatment, teeth were
assigned to four groups: Group 1, nano-hybrid resin composite; Group 2,
polyethylene woven fiber plus nano-hybrid resin composite; Group 3, short fiber
reinforced resin composite plus nano-hybrid resin composite; and Group 4, bulk
fill resin composite plus nano-hybrid resin composite. Then, the teeth were
subjected to the fracture toughness test. The data were analyzed statistically
using one-way ANOVA, followed by Tukey's post-hoc test. The fiber-reinforced
groups had better results than the nano-hybrid and bulk-fill composites (p<0.05),
while the bulk-fill and nano-hybrid composite restorations gave similar results
(p>0.05). Fiber-reinforcement improved the fracture strength of teeth with large
MOD cavities treated endodontically. Bulk-fill composites can be used reliably as
well as nano-hybrid composites.
PMID- 26438987
TI - The effect of zirconia thickness on the biaxial flexural strength of
zirconiaceramic bilayered discs.
AB - The aim of this study was to assess the effect of zirconia core thickness on the
biaxial flexural strength values of zirconia-porcelain bilayered discs. A total
of 60 discs with 0.3, 0.4, and 0.5 mm thickness were obtained from a fully
sintered zirconia block. A 1.5-mm thick layer of veneer porcelain was fired on
the zirconia specimens and biaxial flexural strength tests were performed on the
bilayered discs. In each group, the loading surface was the veneer porcelain in
half of the specimens (core in tension) and the zirconia core surface in the
other half (core in compression). The zirconia core thickness had no effect on
the biaxial flexural strength of zirconiaporcelain bilayered discs when the core
was in tension (p>0.05). Whereas, when the core was in compression, an increase
in the zirconia core thickness resulted in an increase in the biaxial flexural
strength (p<0.05).
PMID- 26438986
TI - Effect of conventional water-bath and experimental microwave polymerization
cycles on the flexural properties of denture base acrylic resins.
AB - The effect of polymerization cycles on flexural properties of conventional (Vipi
Cril((r))-VC) or microwave-processed (Vipi Wave((r))-VW) denture base acrylic
resins was evaluated. Specimens (n=10) were submitted to the cycles: WB=65oC for
1 h+1 h boiling water (VC cycle); M630/25=10 min at 270 W+5 min at 0 W+10 min at
360 W (VW cycle); M650/5=5 min at 650 W; M700/4=4 min at 700 W; and M550/3=3 min
at 550 W. Specimens were submitted to a three-point bending test at 5 mm/min
until fracture. Flexural strength (MPa) and elastic modulus (GPa) data were
analyzed by 2-way ANOVA/Tukey HSD (alpha=0.05). Overall, VC showed higher values
than VW. The results obtained with microwave polymerization did not differ from
those obtained with water-bath for both acrylic resins. The results observed when
polymerization cycles using medium power and shorter time were used did not
differ from those when manufacturer's recommended microwave cycle was applied.
Conventional VC might be microwave-processed without compromising its flexural
properties.
PMID- 26438988
TI - Static and kinetic friction force and surface roughness of different archwire
bracket sliding contacts.
AB - The aim of this study was to determine the static and kinetic friction forces of
the contact bracket-archwire with different dental material compositions in order
to select those materials with lower resistance to sliding. We carried out
sliding friction tests by means of a universal testing machine following an
experimental procedure as described in ASTM D1894 standard. We determined the
static and kinetic friction forces under dry and lubricating conditions using an
artificial saliva solution at 36.5oC. The bracket-archwire pairs studied were:
stainless steel-stainless steel; stainless steel-glass fiber composite; stainless
steel-Nitinol 60; sapphire-stainless steel; sapphire-glass fiber composite; and
sapphire-Nitinol 60. The best performance is obtained for Nitinol 60 archwire
sliding against a stainless steel bracket, both under dry and lubricated
conditions. These results are in agreement with the low surface roughness of
Nitinol 60 with respect to the glass fiber composite archwire. The results
described here contribute to establishing selection criteria for materials for
dental archwire-brackets.
PMID- 26438989
TI - Nanoleakage evaluation at adhesive-dentin interfaces by different observation
methods.
AB - The purpose of this study was to evaluate the capability and characteristics of
different nanoleakage observation methods, including light microscope (LM), field
emission scanning electron microscope (FESEM), transmission electron microscope
(TEM), and confocal laser scanning microscope (CLSM). Dentin specimens were
bonded with either an etch-and-rinse adhesive (SBMP) or a self-etch adhesive
(GB), and prepared for nanoleakge evaluation according to different observation
methods. LM, FESEM and CLSM results demonstrated that the SBMP group showed more
interfacial nanoleakage than the GB group (p<0.05); by contrast, no significant
difference was found in TEM results (p>0.05), however, TEM illustrated concrete
nanoleakage forms or patterns. The results suggested that different observation
methods might exhibit distinct images and a certain degree of variations in
nanoleakage statistical results. Researchers should carefully design and
calculate the optimum assembly in combination with qualitative and quantitative
approaches to obtain objective and accurate nanoleakage evaluation.
PMID- 26438990
TI - Initial and long-term bond strengths of one-step self-etch adhesives with silane
coupling agent to enamel-dentin-composite in combined situation.
AB - This study evaluated the effect of adding silane coupling agent on initial and
long-term bond strengths of one-step self-etch adhesives to enamel-dentin
composite in combined situation. Cervical cavities were prepared on extracted
molars and filled with Clearfil AP-X. After water-storage for one-week, the
filled teeth were sectioned in halves to expose enamel, dentin and composite
surfaces and then enamel-dentin-composite surface was totally applied with one of
adhesive treatments (Clearfil SE One, Clearfil SE One with Clearfil Porcelain
Bond Activator, Beautibond Multi, Beautibond Multi with Beautibond Multi PR Plus
and Scotchbond Universal). After designed period, micro-shear bond strengths
(uSBSs) to each substrate were determined. For each period of water-storage,
additive silane treatments significantly increased uSBS to composite (p<0.001).
On the other hand, they significantly decreased uSBS to dentin (p<0.001),
although did not have adverse effect on uSBS to enamel (p>0.05). Moreover, the
stability of uSBS was depended on materials and substrates used.
PMID- 26438991
TI - Suppression effects of dental glass-ceramics with polarization-induced highly
dense surface charges against bacterial adhesion.
AB - This study investigated the surface characteristics and antibacterial ability
capacity of surface-improved dental glass-ceramics by an electrical polarization
process. Commercially available dental glass-ceramic materials were electrically
polarized to induce surface charges in a direct current field by heating. The
surface morphology, chemical composition, crystal structure, and surface free
energy (SFE) were evaluated using scanning electron microscopy, energy dispersive
X-ray spectrometry, X-ray diffraction, and water droplet methods, respectively.
The antibacterial capacity was assessed by a bacterial adhesion test using
Streptococcus mutans. Although the surface morphology, chemical composition, and
crystal structure were not affected by electrical polarization, the polar
component and total SFE were enhanced. After 24 h incubation at 37oC, bacterial
adhesion to the polarized samples was inhibited. The electrical polarization
method may confer antibacterial properties on prosthetic devices, such as
porcelain fused to metal crowns or all ceramic restorations, without any
additional bactericidal agents.
PMID- 26438992
TI - Machinability of an experimental Ti-Ag alloy in terms of tool life in a dental
CAD/CAM system.
AB - Titanium is difficult to machine because of its intrinsic properties. In a
previous study, the machinability of titanium was improved by alloying with
silver. This study aimed to evaluate the durability of tungsten carbide burs
after the fabrication of frameworks using a Ti-20%Ag alloy and titanium with a
computer-aided design and computer-aided manufacturing system. There was a
significant difference in attrition area ratio between the two metals. Compared
with titanium, the ratio of the area of attrition of machining burs was
significantly lower for the experimental Ti-20%Ag alloy. The difference in the
area of attrition for titanium and Ti-20%Ag became remarkable with increasing
number of machining operations. The results show that the same burs can be used
for a longer time with Ti-20%Ag than with pure titanium. Therefore, in terms of
tool life, the machinability of the Ti-20%Ag alloy is superior to that of
titanium.
PMID- 26438993
TI - Three-dimensional evaluation of the repeatability of scans of stone models and
impressions using a blue LED scanner.
AB - In this study, we evaluated the repeatability of scans of stone models and
impressions of abutment teeth using a blue LED scanner and compared the findings
between different abutment teeth types. For the stone models as well as
impression of the canines, premolars, and molars, we generated 10 color
difference-maps and reports for each tooth type (n=10 per tooth type). One-way
analysis of variance (ANOVA) and independent t-tests were performed to evaluate
the repeatability of scans of the stone models and impressions obtained from a
blue LED scanner. Our results indicate a high repeatability of scans of stone
models and impressions of abutment teeth using the blue LED scanner and suggest a
possible clinical advantage for scanning impressions of different abutment teeth
types.
PMID- 26438994
TI - Hard and soft tissue responses to three different implant materials in a dog
model.
AB - The aim of this study was to assess hard and soft tissue responses using three
dental implants made of different materials. Implants made of titanium (Ti),
yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) and ceria partially
stabilized zirconia/alumina nanocomposite (Ce-TZP/Al2O3) were used in a dog
model. Five male beagles were sacrificed at three months after implantation, and
harvested mandible were observed and analyzed. Histological observations were
similar in all groups. There were no significant differences in any
histomorphometric parameters. Our results suggested the possibility of Ce
TZP/Al2O3 as a dental implant material, similar to Ti and Y-TZP.
PMID- 26438995
TI - Effect of preheating on the viscoelastic properties of dental composite under
different deformation conditions.
AB - Preheating of dental composites improves their flowability, facilitating
successful restorations. However, the flowability of dental composites is
affected not only by temperature but also by the deformation conditions. In the
present work, the effects of various deformation conditions upon the viscoelastic
properties of a preheated dental composite were studied. The rheological
properties of Z350 dental composites at 25, 45, and 60 degrees C were measured by
a strain-controlled rheometer. When a low strain (0.03%) was applied, the
preheated composite exhibited greater shear storage modulus (G') and complex
viscosity (eta*) than a room-temperature composite. Oppositely, when a high
strain (50%) was applied, G' and eta* of a preheated composite were lower than
those of a room-temperature composite. Preheating of dental composites might be
helpful in clinical practice both to increase the slumping resistance when
minimal manipulation is used (e.g., during the build-up of a missing cusp tip)
and to increase flowability when manipulation entailing high shear strain is
applied (e.g., when uncured composite resin is spread on a dentin surface).
PMID- 26438996
TI - Bioactive Co-Cr alloy for biomedical applications prepared by surface
modification using self-assembled monolayers and poly-gamma-glutamic acid.
AB - Cobalt-chromium (Co-Cr) alloys are used in clinical practice for the hard tissue
reconstruction because of their favorable biocompatibility and mechanical
properties. However, their applications have been limited because of their poor
bioactivity, making them poor at bone-bonding. In this study, the bioactivity of
a Co-Cr alloy was evaluated following the immobilization of cross-linked poly
gamma-glutamic acid (gamma-PGA) onto its surface via the formation of 11
aminoundecylphosphonic acid self-assembled monolayers (SAMs). Results of X-ray
photoelectron spectroscopy revealed the presence of a new P2p peak, which
confirms SAMs formation. Furthermore, the surface became highly hydrophobic
following the immobilization with gamma-PGA. Subsequent treatment with CaCl2 at
0.5 M or more and soaking in a simulated body fluid led to the formation of a low
crystalline apatite. The present results show that chemical modification can be
used to induce the formation of an apatite layer on the surface of a Co-Cr alloy
in simulated body fluid.
PMID- 26438997
TI - Calcification of MC3T3-E1 cells on titanium and zirconium.
AB - To confirm similarity of hard tissue compatibility between titanium and
zirconium, calcification of MC3T3-E1 cells on titanium and zirconium was
evaluated in this study. Mirror-polished titanium (Ti) and zirconium (Zr) disks
and zirconium-sputter deposited titanium (Zr/Ti) were employed in this study. The
surface of specimens were characterized using scanning electron microscopy and X
ray diffraction. Then, the cellular proliferation, differentiation and
calcification of MC3T3-E1 cells on specimens were investigated. The surface of
Zr/Ti was much smoother and cleaner than those of Ti and Zr. The proliferation of
the cell was the same among three specimens, while the differentiation and
calcification on Zr/Ti were faster than those on Ti and Zr. Therefore, Ti and Zr
showed the identical hard tissue compatibility according to the evaluation with
MC3T3-E1 cells. Sputter deposition may improve cytocompatibility.
PMID- 26438998
TI - Halloysite Clay Nanotubes for Loading and Sustained Release of Functional
Compounds.
AB - Halloysite is an alumosilicate tubular clay with a diameter of 50 nm, an inner
lumen of 15 nm and a length of 600-900 nm. It is a natural biocompatible
nanomaterial available in thousands of tons at low price, which makes it a good
candidate for nanoarchitectural composites. The inner lumen of halloysite may be
adjusted by etching to 20-30% of the tube volume and loading with functional
agents (antioxidants, anticorrosion agents, flame-retardant agents, drugs, or
proteins) allowing for formulations with sustained release tuned by the tube end
stoppers for hours and days. Clogging the tube ends in polymeric composites
allows further extension of the release time. Thus, antioxidant-loaded halloysite
doped into rubber enhances anti-aging properties for at least 12 months. The
addition of 3-5 wt% of halloysite increases the strength of polymeric materials,
and the possibility of the tube's orientation promises a gradient of properties.
Halloysite nanotubes are a promising mesoporous media for catalytic nanoparticles
that may be seeded on the tube surface or synthesized exclusively in the lumens,
providing enhanced catalytic properties, especially at high temperatures. In
vitro and in vivo studies on biological cells and worms indicate the safety of
halloysite, and tests for efficient adsorption of mycotoxins in animals' stomachs
are also carried out.
PMID- 26438999
TI - Process Analytical Utility of Raman Microspectroscopy in the Directed
Differentiation of Human Pancreatic Insulin-Positive Cells.
AB - Continued advances toward cell-based therapies for human disease generate a
growing need for unbiased and label-free monitoring of cellular characteristics.
We used Raman microspectroscopy to characterize four important stages in the 26
day directed differentiation of human embryonic stem cells (hESCs) to insulin
positive cells. The extent to which the cells retained spectroscopic features of
pluripotent cells or developed spectroscopic features suggestive of pancreatic
endocrine cells, as well as assessing the homogeneity of the cell populations at
these developmental stages, were of particular interest. Such information could
have implications for the utility of Raman microspectroscopy process analysis for
the generation of insulin-positive cells from hESCs. Because hESC seeding density
influences the subsequent pancreatic development, three different seeding density
cultures were analyzed. Transcription factor and other marker analyses assessed
the progress of the cells through the relevant developmental stages. Increases in
the Raman protein-to-nucleic acid band ratios were observed at the final
endocrine stage analyzed, but this increase was less than expected. Also, high
glycogen band intensities, somewhat unexpected in pancreatic endocrine cells,
suggested the presence of a substantial number of glycogen containing cells. We
discuss the potential process analytical technology application of these findings
and their importance for cell manufacturing.
PMID- 26439000
TI - Novel microsatellite marker development from the unassembled genome sequence data
of the marbled flounder Pseudopleuronectes yokohamae.
AB - Various genome-scale data have been increasingly published in diverged species,
but they can be reused for other purposes by re-analyzing in other ways. As a
case study to utilize the published genome data, we developed microsatellite
markers from the genome sequence data (assembled contigs and unassembled reads)
of the marbled flounder Pseudopleuronectes yokohamae. No microsatellites were
identified in the contig sequences, whereas the computer software found 781,773
sequences containing microsatellites with di- to hexa-nucleotide motif in the
unassembled reads. For 86,732 unique sequences among them, a total of 331,368
primer pairs were designed. Screening based on PCR amplification, polymorphisms
and accurate genotyping resulted in sixteen primer sets, which were later
characterized using 45 samples collected in Onagawa Bay, Miyagi, Japan. The
presence of null alleles was suggested at four loci in the studied population but
no evidence of allelic dropout was found. The observed number of alleles and
heterozygosity was 2-20 and 0-0.88889, respectively, indicating polymorphisms and
usefulness for population genetic analyses of this species. In addition, a large
number of the microsatellite primers developed in this study are potentially
applicable also for kinship estimation, individual fingerprint and linkage map
construction.
PMID- 26439001
TI - MIFEPRISTONE AND CUSHING SYNDROME: A COMMENTARY.
PMID- 26439002
TI - DRIVING UP THE DOSE: IMPLICATIONS FOR HIGH-DOSE VITAMIN D THERAPY.
PMID- 26439003
TI - PANCREATIC KETOACIDOSIS (KABADI SYNDROME) MIMICKING DIABETIC KETOACIDOSIS.
PMID- 26439004
TI - A PHYSICAL EXAMINATION MANEUVER THAT FACILITATES PALPATION OF CERVICAL
LYMPHADENOPATHY.
PMID- 26439005
TI - Correction.
PMID- 26439006
TI - Delivery of human mesenchymal adipose-derived stem cells restores multiple
urological dysfunctions in a rat model mimicking radical prostatectomy damages
through tissue-specific paracrine mechanisms.
AB - Urinary incontinence (UI) and erectile dysfunction (ED) are the most common
functional urological disorders and the main sequels of radical prostatectomy
(RP) for prostate cancer. Mesenchymal stem cell (MSC) therapy holds promise for
repairing tissue damage due to RP. Because animal studies accurately replicating
post-RP clinical UI and ED are lacking, little is known about the mechanisms
underlying the urological benefits of MSC in this setting. To determine whether
and by which mechanisms MSC can repair damages to both striated urethral
sphincter (SUS) and penis in the same animal, we delivered human multipotent
adipose stem cells, used as MSC model, in an immunocompetent rat model
replicating post-RP UI and ED. In this model, we demonstrated by using
noninvasive methods in the same animal from day 7 to day 90 post-RP injury that
MSC administration into both the SUS and the penis significantly improved urinary
continence and erectile function. The regenerative effects of MSC therapy were
not due to transdifferentiation and robust engraftment at injection sites.
Rather, our results suggest that MSC benefits in both target organs may involve a
paracrine process with not only soluble factor release by the MSC but also
activation of the recipient's secretome. These two effects of MSC varied across
target tissues and damaged-cell types. In conclusion, our work provides new
insights into the regenerative properties of MSC and supports the ability of MSC
from a single source to repair multiple types of damage, such as those seen after
RP, in the same individual.
PMID- 26439007
TI - Impact of a decade of successful antiretroviral therapy initiated at HIV-1
seroconversion on blood and rectal reservoirs.
AB - Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure.
Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs
and allow for virological control after ART discontinuation. We compared HIV-1
reservoirs in a cross-sectional study using polymerase chain reaction-based
techniques in blood and tissue of early-treated seroconverters, late-treated
patients, ART-naive seroconverters, and long-term non-progressors (LTNPs) who
have spontaneous virological control without treatment. A decade of early ART
reduced the total and integrated HIV-1 DNA levels compared with later treatment
initiation, but not reaching the low levels found in LTNPs. Total HIV-1 DNA in
rectal biopsies did not differ between cohorts. Importantly, lower viral
transcription (HIV-1 unspliced RNA) and enhanced immune preservation (CD4/CD8),
reminiscent of LTNPs, were found in early compared to late-treated patients. This
suggests that early treatment is associated with some immunovirological features
of LTNPs that may improve the outcome of future interventions aimed at a
functional cure.
PMID- 26439008
TI - Structure and conformational states of the bovine mitochondrial ATP synthase by
cryo-EM.
AB - Adenosine triphosphate (ATP), the chemical energy currency of biology, is
synthesized in eukaryotic cells primarily by the mitochondrial ATP synthase. ATP
synthases operate by a rotary catalytic mechanism where proton translocation
through the membrane-inserted FO region is coupled to ATP synthesis in the
catalytic F1 region via rotation of a central rotor subcomplex. We report here
single particle electron cryomicroscopy (cryo-EM) analysis of the bovine
mitochondrial ATP synthase. Combining cryo-EM data with bioinformatic analysis
allowed us to determine the fold of the a subunit, suggesting a proton
translocation path through the FO region that involves both the a and b subunits.
3D classification of images revealed seven distinct states of the enzyme that
show different modes of bending and twisting in the intact ATP synthase.
Rotational fluctuations of the c8-ring within the FO region support a Brownian
ratchet mechanism for proton-translocation-driven rotation in ATP synthases.
PMID- 26439009
TI - A mutation uncouples the tubulin conformational and GTPase cycles, revealing
allosteric control of microtubule dynamics.
AB - Microtubule dynamic instability depends on the GTPase activity of the
polymerizing alphabeta-tubulin subunits, which cycle through at least three
distinct conformations as they move into and out of microtubules. How this
conformational cycle contributes to microtubule growing, shrinking, and switching
remains unknown. Here, we report that a buried mutation in alphabeta-tubulin
yields microtubules with dramatically reduced shrinking rate and catastrophe
frequency. The mutation causes these effects by suppressing a conformational
change that normally occurs in response to GTP hydrolysis in the lattice, without
detectably changing the conformation of unpolymerized alphabeta-tubulin. Thus,
the mutation weakens the coupling between the conformational and GTPase cycles of
alphabeta-tubulin. By showing that the mutation predominantly affects post-GTPase
conformational and dynamic properties of microtubules, our data reveal that the
strength of the allosteric response to GDP in the lattice dictates the frequency
of catastrophe and the severity of rapid shrinking.
PMID- 26439010
TI - TAPBPR alters MHC class I peptide presentation by functioning as a peptide
exchange catalyst.
AB - Our understanding of the antigen presentation pathway has recently been enhanced
with the identification that the tapasin-related protein TAPBPR is a second major
histocompatibility complex (MHC) class I-specific chaperone. We sought to
determine whether, like tapasin, TAPBPR can also influence MHC class I peptide
selection by functioning as a peptide exchange catalyst. We show that TAPBPR can
catalyse the dissociation of peptides from peptide-MHC I complexes, enhance the
loading of peptide-receptive MHC I molecules, and discriminate between peptides
based on affinity in vitro. In cells, the depletion of TAPBPR increased the
diversity of peptides presented on MHC I molecules, suggesting that TAPBPR is
involved in restricting peptide presentation. Our results suggest TAPBPR binds to
MHC I in a peptide-receptive state and, like tapasin, works to enhance peptide
optimisation. It is now clear there are two MHC class I specific peptide editors,
tapasin and TAPBPR, intimately involved in controlling peptide presentation to
the immune system.
PMID- 26439011
TI - Odor-identity dependent motor programs underlie behavioral responses to odors.
AB - All animals use olfactory information to perform tasks essential to their
survival. Odors typically activate multiple olfactory receptor neuron (ORN)
classes and are therefore represented by the patterns of active ORNs. How the
patterns of active ORN classes are decoded to drive behavior is under intense
investigation. In this study, using Drosophila as a model system, we investigate
the logic by which odors modulate locomotion. We designed a novel behavioral
arena in which we could examine a fly's locomotion under precisely controlled
stimulus condition. In this arena, in response to similarly attractive odors,
flies modulate their locomotion differently implying that odors have a more
diverse effect on locomotion than was anticipated. Three features underlie odor
guided locomotion: First, in response to odors, flies modulate a surprisingly
large number of motor parameters. Second, similarly attractive odors elicit
changes in different motor programs. Third, different ORN classes modulate
different subset of motor parameters.
PMID- 26439012
TI - Snf1/AMPK promotes the formation of Kog1/Raptor-bodies to increase the activation
threshold of TORC1 in budding yeast.
AB - The target of rapamycin complex I (TORC1) regulates cell growth and metabolism in
eukaryotes. Previous studies have shown that nitrogen and amino acid signals
activate TORC1 via the small GTPases, Gtr1/2. However, little is known about the
way that other nutrient signals are transmitted to TORC1. Here we report that
glucose starvation triggers disassembly of TORC1, and movement of the key TORC1
component Kog1/Raptor to a single body near the edge of the vacuole. These events
are driven by Snf1/AMPK-dependent phosphorylation of Kog1 at Ser 491/494 and two
nearby prion-like motifs. Kog1-bodies then serve to increase the threshold for
TORC1 activation in cells that have been starved for a significant period of
time. Together, our data show that Kog1-bodies create hysteresis (memory) in the
TORC1 pathway and help ensure that cells remain committed to a quiescent state
under suboptimal conditions. We suggest that other protein bodies formed in
starvation conditions have a similar function.
PMID- 26439013
TI - It takes two.
AB - Two forms of an unconventional myosin motor protein have separate functions in
the growth and maintenance of hair bundles in auditory hair cells.
PMID- 26439014
TI - Fistula of the Stump: A Novel Approach With a "Stapled" Stent.
AB - Postoperative bronchopleural fistulas are serious and uncommon complications
after pneumonectomy. Available therapeutic approaches are medical, endoscopic,
and/or surgical. A 42-year-old man underwent left pneumonectomy. Three years
later he was admitted to an intensive care unit with pneumonia of the remaining
lung, severe respiratory insufficiency, and a bronchopleural fistula with an air
fluid level filling in the pneumonectomy cavity. A left chest drain was placed,
and broad-spectrum antibiotics and mechanical ventilation were administered.
Because of the unstable clinical condition, a blind end endobronchial stent
closed by a stapler was placed in the left bronchial stump. He improved in a
couple of months and underwent definitive surgical sealing of the
fistula.Endoscopic interventions are usually safe and free from associated
complications. They are an excellent option, when patient's clinical condition is
contraindication to immediate surgery.
PMID- 26439015
TI - Pulmonary Varices in an Adult.
PMID- 26439016
TI - Safety and Clinical Utility of Flexible Bronchoscopic Cryoextraction in Patients
With Non-neoplasm Tracheobronchial Obstruction: A Retrospective Chart Review.
AB - BACKGROUND: Airway obstruction from blood clots, airway secretions, and foreign
bodies is a potentially life-threatening condition. Optimal management of this
problem, whether by rigid or flexible bronchoscopy, has not been well studied. We
report our single-center experience on the safety and clinical utility of
cryoprobe extraction for this indication. METHODS: We performed a retrospective
chart review from January 2006 to November 2014 of all subjects aged 18 and older
who underwent flexible bronchoscopic cryoprobe extraction. Subjects with
obstruction due to benign or malignant neoplasm or airway stenosis were excluded.
RESULTS: A total of 38 cryotherapy sessions performed on 30 subjects were
identified for inclusion. Cryoprobe extraction was successful in reestablishing
airway patency in 32/38 (84%) sessions overall and in 24/26 (92%) for blood
clots, 4/6 (67%) for mucous plugging, 2/4 (50%) for foreign bodies, and 2/2
(100%) for plastic bronchitis. Twenty-one of 31 (68%) sessions resulted in
improvement in oxygenation or ventilation. There was 1 complication related to
sedation. CONCLUSIONS: We conclude that flexible bronchoscopic cryoprobe
extraction of blood clots, mucous secretions, plastic bronchitis, and foreign
bodies is a safe and effective option. It can be safely performed at the bedside
and in many cases eliminates the need for rigid bronchoscopy.
PMID- 26439017
TI - Coupling hybridization chain reaction with catalytic hairpin assembly enables non
enzymatic and sensitive fluorescent detection of microRNA cancer biomarkers.
AB - The identification and quantification of sequence-specific microRNAs (miRNAs)
plays an important role in early diagnosis of different diseases. In this work,
by integrating two independent signal amplification approaches, hybridization
chain reaction and catalytic hairpin assembly, we report an enzyme-free and dual
amplified approach for highly sensitive detection of a human prostate cancer
biomarker, miR-141. The presence of miR-141 triggers the self-assembly of two
hairpin DNAs into dsDNA polymers, which co-localize two split segments of ssDNA
into proximity. Subsequently, these co-localized ssDNA sequences further act as
triggers to initiate catalytic assembly of two fluorescently quenched hairpin
DNAs to form numerous dsDNA strands, resulting in the recovery of the fluorescent
emissions and remarkably amplified signals for highly sensitive detection of miR
141 down to 0.3 fM. In addition, this method is also selective for the target
miRNA against other control sequences. With the advantages of high sensitivity
and nanomaterial/enzyme-free detection format, the developed method can be a
general sensing platform for the detection of trace amounts of sequence-specific
nucleic acid targets.
PMID- 26439018
TI - Mitochondrial enzyme dysfunction in autism spectrum disorders; a novel biomarker
revealed from buccal swab analysis.
AB - AIM: Mitochondrial function studies in autism spectrum disorders (ASD) have
detected skeletal muscle mitochondrial enzyme deficiencies in respiratory complex
(RC) activities. As a muscle biopsy is expensive and invasive, we assessed RC-I
and RC-IV activities in buccal swabs. METHODS: 92 children with ASD and 68
controls were studied with immunocapture for RC-I and microspectrophotometry for
RC-IV. RESULTS: Significant RC activity deficiencies were found in 39 (42%) ASD
patients (p < 0.01) and more prevalent in more severe cases. Aberrant RC
overactivity was seen in 9 children. RC-I/RC-IV activity ratio was significantly
increased in 64% of the entire ASD cohort including 76% of those more severely
affected (p < 0.05). CONCLUSION: Buccal swab analysis revealed extensive RC
abnormalities in ASD providing a noninvasive biomarker to assess mitochondrial
function in ASD patients.
PMID- 26439019
TI - The pursuit of excellence in a climate of cost containment.
PMID- 26439020
TI - Evaluation of cytotoxicity of some common ophthalmic drugs.
AB - The article "Evaluation of cytotoxicity of some common ophthalmic drugs" by M.
Li, X.-M. Chen, J.-J. Liu, D.-M. Wang, L. Gan, X. Lv, Y. Qiao, published in Eur
Rev Med Pharmacol Sci 2015; 19 (11): 1945-1950 has been withdrawn.
PMID- 26439021
TI - Respiratory cancers and pollution.
PMID- 26439022
TI - Plasma rich in growth factors (PRGF) technology: simple facts that turn on the
lights.
PMID- 26439023
TI - What is the actual prevalence and clinical characteristics of mitral valve
prolapse?
PMID- 26439024
TI - Low prevalence of mitral valve prolapse in a population-based epidemiologic
study.
PMID- 26439025
TI - Bioinformatic analysis of the microarray gene expression profile in degenerative
intervertebral disc cells exposed to TNF-alpha.
AB - OBJECTIVE: We performed a bioinformatic analysis of the microarray data on the
gene expression profiles of degenerative intervertebral disc cells after exposure
to tumor necrosis factor-alpha (TNF-alpha) to uncover the key genes that were
differentially expressed between cells with and without exposure, and to explore
the related signaling pathways and interaction networks, providing clues for
future investigations on the molecular mechanisms of disc degeneration. MATERIALS
AND METHODS: The microarray data for degenerative intervertebral disc cells after
stimulation with TNF-alpha were downloaded from a public database, the GEO (Gene
Expression Omnibus), in order to identify the genes that were differentially
expressed between untreated degenerative disc cells and those stimulated with TNF
alpha, and then analyses of the gene ontology, signaling pathways and interaction
networks for the differentially expressed genes were conducted using the DAVID,
STRING and other online tools. RESULTS: A total of 753 differentially expressed
genes were found in the degenerative annulus fibrosus disci intervertebralis
cells after stimulation with TNF-alpha, including 458 upregulated genes and 295
downregulated genes. The Gene Ontology annotation analysis showed that these
differentially expressed genes were mainly associated with the extracellular
matrix, damage reactions, inflammatory reactions, and the regulation of
apoptosis. A signaling pathway analysis showed that these differentially
expressed genes were mainly involved in the interactions of cytokines, apoptosis,
NOD-like receptors, chemokines, and other signal transduction pathways. The
interaction network analysis indicated that JUN, CCL3, ANHK and other genes may
play key roles in intervertebral disc degeneration. CONCLUSIONS: The
bioinformatic analysis of the gene expression profiles of degenerative
intervertebral disc cells stimulated with TNF-alpha showed that CCL3 and other
genes may play a role in the development of the disc degeneration induced by
inflammatory reactions. This suggests that bioinformatics methods can be used to
identify potential therapeutic target genes, and to provide new insight into
intervertebral disc degeneration.
PMID- 26439026
TI - Current trends in spinal cord injury repair.
AB - One of the rapidly prevailing neurological disorders affecting thousands of
people per year is spinal cord injury (SCI). Though, great research has been made
in recent past to understand thoroughly the molecular bases of the diseases, no
fully restorative treatments for SCI are available. However, various
rehabilitative, cellular and molecular therapies are being tested in animal
models. Some of them have shown promising results. So, the present review shall
enlighten all these latest developments in the field of spinal cord injury
repair. The review shall discuss latest upcoming areas being focused for the
management of SCI patients like stem cell therapy approach, cell-based
approaches, combination therapeutic approaches, neuronal plasticity and possible
use of omega-3 fatty acids in SCI repair.
PMID- 26439027
TI - Preliminary study of IVIM-DWI and DCE-MRI in early diagnosis of esophageal
cancer.
AB - OBJECTIVE: To investigate the application value of double exponential model
diffusion weighted imaging (IVIM-DWI) and dynamic contrast enhanced magnetic
resonance imaging (DCE-MRI) in the diagnosis of early esophageal cancer. PATIENTS
AND METHODS: 30 cases of patients with early esophageal cancer confirmed by
pathology were collected. They were performed MRI plain scan, IVIM-DWI and DCE
MRI scan. The normal esophageal tissue, SlowADC value in tumor focus, FastADC
value, F value, Ktrans, Kep and Ve values were measured. The difference between
cancer tissue and normal tissue was compared using two independent sample t test.
The prediction parameters and diagnostic threshold were compared by drawing
receiver operating characteristic curve (ROC). RESULTS: The average F, Ktrans and
Kep values in esophageal cancer and normal esophageal tissue were: (0.48 +/-
0.19), (0.64 +/- 0.08); (0.45 +/- 0.19)/min, (0.14 +/- 0.04)/min and (1.14 +/-
0.42)/min, (0.56 +/- 0.25)/min respectively. Compared with normal esophageal
tissue, esophageal cancer F value decreased, Ktrans value increased, Kep value
increased, and the difference was statistically significant (p < 0.05); There was
no difference in SlowADC, FastADC, Ve values of esophageal cancer and those in
normal esophageal tissues (p > 0.05). The areas under ROC curve F, Ktrans and Kep
values were 0.90, 0.98 and 0.92 respectively. They had the higher diagnostic
efficiency. CONCLUSIONS: IVIM-DWI and DCE-MRI can be used as the imaging method
to diagnose esophageal malignant tumor, which has the higher diagnostic value.
PMID- 26439028
TI - Effect of personalized dietary intervention on nutritional, metabolic and
vascular indices in patients with chronic kidney disease.
AB - OBJECTIVE: Patients with chronic kidney disease (CKD) present a markedly
increased cardiovascular (CV) morbidity and mortality since the early stages of
the disease and a high prevalence of malnutrition, inflammation, and accelerated
atherosclerosis. Personalized nutritional intervention, with of a low-protein
diet (LPD), since the early stages of CKD should be able to achieve significant
metabolic improvements. In our study we have verified the effects of a
personalized dietary intervention in patients in the CKD stages 3/4 KDOQI on
nutritional, metabolic and vascular indices. PATIENTS AND METHODS: We have
evaluated renal function, lipid profile, mineral metabolism, inflammatory
indices, and acid-base balance of 16 patients with CKD (stages 3/4 KDOQI).
Assessment of nutritional status, body composition, bone mineral density and
muscle mass, using body mass index (BMI), handgrip strength, bioelectrical
impedance analysis (BIA), and dual energy X-ray absorptiometry (DEXA) was
performed. Vascular indices and endothelial dysfunction such as carotid intima
media thickness (cIMT) and the brachial artery flow-mediated dilation (baFMD)
were also analyzed. RESULTS: After dietary interventions, we observed a
significant increase in plasma bicarbonate (p = 0.004) and vitamin D levels (p =
0.03) and a concomitant significant reduction of phosphorus concentration (p =
0.001) and C-reactive protein (CRP) (p = 0.01). CONCLUSIONS: Nutritional
intervention potentially plays a major role in reducing the progression of CKD
and systemic complications of predialysis patients. A low-protein diet (LPD)
ensuring vegetable protein intake and a reduced amount of specific micronutrients
should be recommended to stage 3/4 CKD patients in order to ameliorate metabolic
profile, renal outcome, and reduce cardiovascular risk factors.
PMID- 26439029
TI - Prognostic significance of flow cytometry findings in Turkish adult acute
leukemia patients.
AB - OBJECTIVE: Several factors are known to affect prognosis of acute leukemia such
as age, high leukocyte count, cytogenetic abnormality, performance status and
recurrent leukemia. We aimed to investigate the association between cell surface
markers and prognostic determinants such as recurrence at 6 and 12 months and
survival at 6, 12 and 18 months in acute leukemia patients. PATIENTS AND METHODS:
A total of 142 patients, 101 with acute myeloid leukemia (AML) and 41 with B-cell
acute lymphoblastic leukemia (B-ALL) were included. The effects of surface
markers on survival and recurrence rates were evaluated retrospectively. RESULTS:
In AML patients, CD5+ and CD34+ immunophenotypes and in ALL patients cCD22+,
CD34+ and CD49f + CD19+ immunophenotypes were positive prognostic indicators. In
AML patients CD7 expression, and in ALL patients CD5+, CD7+ and CD117+
immunophenotypes and >90% CD45 expression were negative prognostic indicators.
CONCLUSIONS: This study demonstrates that flow cytometry, a common diagnostic
tool in acute leukemia, may also have prognostic value in acute leukemia in the
future.
PMID- 26439030
TI - Microarray based analysis of gene expression patterns in pancreatic
neuroendocrine tumors.
AB - OBJECTIVE: Pancreatic neuroendocrine tumors (PanNETs) are a small subgroup of
tumors with a variety of biological behaviors. MATERIALS AND METHODS: We sought
to identify the specially expressed genes and characterize significant pathways
in PanNETs compared with non-neoplastic samples. Gene expression profile GSE43795
was obtained from Gene Expression Omnibus database, which included 6 PanNETs and
5 non-neoplastic samples. The differentially expressed genes (DEGs) were
identified using Limma package. Gene Ontology (GO) and Kyoto Encyclopedia of
Genes and Genomes (KEGG) enrichment analyses were used to enrich the functions
and pathways of DEGs. Transcription factors (TFs) and tumor-associated genes
(TAGs) were also identified. Finally, a protein-protein interaction (PPI) network
was constructed, and hub proteins and functional module were screened out.
RESULTS: Total of 821 DEGs (421 down-regulated, 400 up-regulated) were selected.
GO and KEGG enrichment analyses showed that up-regulated DEGs were related to
several pathways, including type 2 diabetes mellitus, Ca2+ signaling pathway,
long-term potentiation, and long-term depression pathways. Down-regulated DEGs
were enriched in several pathways, such as pancreatic secretion, protein
digestion and absorption, and metabolic pathway. Interferon-stimulated gene
protein 15 (ISG15), somatostatin (SST), and synaptosomal-associated protein 25
kDa (SNAP25) were identified as hub proteins. CONCLUSIONS: The genes involved in
type 2 diabetes mellitus pathway may play important roles in the development of
PanNETs. SNAP25, SST, and ISG15 may be used as potential targets for treatment of
PanNETs.
PMID- 26439031
TI - Identification of potential therapeutic target genes and mechanisms in non-small
cell lung carcinoma in non-smoking women based on bioinformatics analysis.
AB - OBJECTIVE: The study was aimed to explore the underlying mechanisms and identify
the potential target genes by bioinformatics analysis for non-small-cell lung
carcinoma (NSCLC) treatment in non-smoking women. MATERIALS AND METHODS: The
microarray data of GSE19804 was downloaded from Gene Expression Omnibus (GEO)
database. Paired samples (from the same patient) of tumor and normal lung tissues
from 60 non-smoking female NSCLC patients were used to identify differentially
expressed genes (DEGs). The functional enrichment analysis was performed.
Furthermore, the protein-protein interaction (PPI) network of the DEGs was
constructed by Cytoscape software. The module analysis was performed. RESULTS:
Totally, 817 DEGs including 273 up- and 544 down-regulated genes were identified.
The up-regulated genes were mainly enriched in extracellular matrix (ECM)
receptor interaction, focal adhesion and cell cycle functions, while down
regulated genes were mainly enriched in the cytokine-cytokine receptor
interaction pathway. DEGs including hyaluronan-mediated motility receptor (HMMR),
collagen, type I alpha 2 (COL1A2), cyclin A2 (CCNA2), MAD2 mitotic arrest
deficient-like 1 (MAD2L1), interleukin 6 (IL6) and interleukin 1, beta (IL1B)
were identified in these functions. These genes were hub nodes in PPI networks.
Besides, there were 3 up-regulated modules and 1 down-regulated module. The
significant pathways were ECM-receptor interaction and focal adhesion in up
regulated modules, while in down-regulated module, the significant pathway was
mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: The ECM
receptor interaction, focal adhesion, cell cycle and cytokine-cytokine receptor
interaction functions may be associated with NSCLC development. Genes such as
HMMR, COL1A2, CCNA2, MAD2L1, IL6 and IL1B may be potential therapeutic target
genes for NSCLC.
PMID- 26439032
TI - Serum nerve growth factor level indicates therapeutic efficacy of 125I seed
implantation in advanced pancreatic adenocarcinoma.
AB - OBJECTIVE: To evaluate serum nerve growth factor (NGF) as a marker in predicting
effectiveness of 125I seed implantation in advanced pancreatic carcinoma.
PATIENTS AND METHODS: A total of 45 patients (30 males/15 females with mean age
of 52.07+/-8.43 years) diagnosed with advanced pancreatic adenocarcinoma (PCa)
between January 2011 to May 2014 were enrolled as PCa group in this study. Tumors
were categorized as at least stage III with unresectionable condition by the TNM
standard. The average tumour shortest diameter was 37.54+/-13.84 mm (18.50-71.20
mm). NGF level in serum before 125I seed implantation and in tumor tissue
resected during surgery was measured by ELISA. After treatment, CT Scan was used
to serially monitor the diameters of the tumour monthly for 6-month follow-up.
RECIST was applied to evaluate the efficacy. Predictive value of serum and tumour
derived NGF was evaluated based on ROC curve chart. RESULTS: We found that the
serum NGF level was significantly increased in PCa patients (775.60 +/- 250.97
pg/ml) compared to the healthy control group (35.03 +/- 25.36 pg/ml), after age
and gender adjustment. In the PCa group, the serum NGF level positively
correlated with that from loci tumor tissue (r=0.487). The serum NGF level was
compared between the effective group (537.42 +/- 122.61 pg/ml) and noneffective
group (883.17 +/- 217.79 pg/ml), and significant difference was detected
(p<0.0001). Patients with lower serum NGF level had good response to the 125I
seeds implantation. Taking cut-off at 649.59 pg/ml, 85.70% specificity and 90.30%
sensitivity were achieved by ROC. Area under the Curve of serum NGF was 0.945,
standard deviation was 0.032, 95% confidence interval was 0.882-1.000.
CONCLUSIONS: The level of serum NGF could be a referential index to predict the
therapeutic efficacy of 125I seed implantation treatments in advanced pancreatic
adenocarcinoma.
PMID- 26439033
TI - Tegafur gimeracil oter combined with oxaliplatin for advanced colorectal cancer.
AB - OBJECTIVE: To analyze the therapeutic actions of tegafur gimeracil oteracil
combined with oxaliplatin for treating patients with advanced colorectal cancer,
and its effects on the K-ras gene mutation and the CK20 mRNA. PATIENTS AND
METHODS: Forty-one patients with advanced colorectal cancer from our hospital,
from October 2013 to October 2014, were enrolled in this study. After obtaining
consent from the hospital Ethics Committee and the patients as well as their
relatives, all 41 patients were divided into two groups. The control group, which
consisted of 20 cases, were treated with capecitabine combined with oxaliplatin.
The study group, which comprised of 21 cases, were treated with tegafur gimeracil
oteracil combined with oxaliplatin. Both groups were followed-up after six months
to evaluate the treatment outcomes. RESULTS: The survival rate in the observation
group was higher than that in the control group. The progression-free survival
time (PFS) in the observation group was longer than that in the control group.
The objective response rate (ORR) and disease control rate (DCR) were higher for
the observation group. The differences had statistical significance (p < 0.05).
The proportion of K-ras gene mutation in the observation group was substantially
superior to that in the control group. The positive expression rate of CK 20 mRNA
in the observation group was significantly lower than that in the control group.
The differences had statistical significance (p < 0.05). The incidence of adverse
reaction in the observation group was lower than that of the control group, and
the differences had statistical significance (p < 0.05). CONCLUSIONS:
Tegafur/gimeracil/oteracil combined with oxaliplatin therapy had better treatment
outcomes than capecitabine combined oxaliplatin for advanced colorectal cancer.
This maybe related to K-ras gene mutation and the reduction of CK20 mRNA
expression.
PMID- 26439034
TI - Overexpression of microRNA-21 in peripheral blood mononuclear cells of patients
with B-cell non-Hodgkin's lymphoma is associated with disease stage and treatment
outcome.
AB - OBJECTIVE: We wished to assess the association between microRNA-21 (miR-21) and
disease stage and treatment outcome in patients with B-cell non-Hodgkin's
Lymphoma (B-NHL). PATIENTS AND METHODS: A total of consecutive 128 patients with
B-NHL were enrolled; 30 healthy individuals served as controls. qPCR assay was
utilized to quantify expression levels of miR-21 in peripheral blood mononuclear
cells (PBMC; Ficoll isolation protocol). Expression of the miR-21 target,
phosphatase and tensin homolog (PTEN), was assessed by Western blot analysis.
RESULTS: miR-21 was overexpressed in PBMC of patients with B-NHL (p < 0.05 vs.
healthy individuals). Furthermore, miR-21 expression levels were significantly
higher in patients with the stage III/IV B-NHL (p < 0.05 vs. stage I/II B-NHL).
After chemotherapy, miR-21 expression levels were significantly decreased in
patients in complete remission and became comparable to those of healthy
individuals. Also, miR-21 expression levels were lower in patients treated with
chemotherapy combined with rituximab. There was a negative association between
miR-21 overexpression and post-chemotherapy survival rates of the patients.
Expression of PTEN was significantly lower in patients with B-NHL (p < 0.05 vs.
healthy individuals). CONCLUSIONS: Overexpression of miR-21 is associated with
disease stage and treatment outcome of B-NHL. This potentially involves negative
modulation of PTEN.
PMID- 26439035
TI - Long noncoding RNA UCA1 modulates breast cancer cell growth and apoptosis through
decreasing tumor suppressive miR-143.
AB - OBJECTIVE: Long non coding RNA (LncRNA) urothelial carcinoma-associated 1 (UCA1)
is an oncogene in breast cancer. However, the detailed mechanism has not been
fully revealed. This study explored whether UCA1 can directly interact with miR
143, a tumor suppressor in breast cancer and whether the UCA1-miR-143 axis is
involved in regulation of cancer cell growth and apoptosis. PATIENTS AND METHODS:
miRNA microarray was performed to identify the most dysregulated miRNAs between
tumor and adjacent normal tissues of breast cancer. QRT-PCR analysis was
performed to assess the expression of UCA1 and miR-143. The binding between UCA1
and miR-143 was verified using dual luciferase and RNA binding protein
immunoprecipitation (RIP) assay. MTT assay and flow cytometry analysis were
performed to study the role of UCA1-miR-143 axis in cell proliferation, cell
cycle and apoptosis. RESULTS: UC1 was significantly upregulated, while miR-143
was significantly downregulated in the tumor tissues than in the adjacent normal
tissues. There are direct interactions between miR-143 and the miRNA recognition
sites of UCA1. UCA1 is present in Ago2-containing RNA-induced silencing complex
(RISC), through association with miR-143. Through downregulating miR-143, UCA1
can modulate breast cancer cell growth and apoptosis. CONCLUSIONS: UCA1 can
directly interact with miR-143, lower its expression and affect its downstream
regulation. Therefore, the UCA1-miR-143 axis constitutes a part of the oncogenic
role of UCA1 in breast cancer.
PMID- 26439036
TI - microRNA-106a induces the proliferation and apoptosis of glioma cells through
regulating JNK/MAPK pathway.
AB - OBJECTIVE: To investigate the expression of microRNA-106a (miRNA-106a) in the
brain tissue and the plasma of glioma patients, and explore the mechanism
underlying the effect of miRNA-106a on the proliferation and apoptosis of glioma
cells. PATIENTS AND METHODS: Brain tissues from 42 glioma patients admitted in
our institution were included in study group, whereas normal brain tissues
collected from 10 patients undergoing brain tissue resection due to decompression
or exposure during cerebral surgery. Quantitative fluorescent RT-PCR (QF RT-PCR)
was performed to measure miRNA-106a mRNA levels in the brain tissue and
peripheral blood of patients in two groups. Human M059K glioma cells were
transfected with miRNA-106a mimic and inhibitor, and the proliferation and
apoptosis of glioma cells were analyzed. In addition, JNK/MAPK in glioma cells
was examined at mRNA and protein levels. RESULTS: Compared with the normal
population, miRNA-106a expression was significantly increased in the brain tissue
of glioma patients (p < 0.05). Besides, miRNA-106a expression level was
significantly elevated in the plasma of peripheral blood of glioma patients (p <
0.05). After the interference of miRNA-106a in M059K glioma cells, the
proliferation of glioma cells was significantly reduced. However, the apoptotic
regulatory factor, Bcl-2, was significantly increased, and JNK/MAPK protein level
was significantly decreased. Overexpression of miRNA-106a in glioma cells
resulted in significant increase in the proliferation of glioma cells and
JNK/MAPK protein level, but obvious suppression in Bcl-2 protein level.
CONCLUSIONS: Elevated expression of miRNA-106a plays a crucial role in the
development and progression of glioma, probably by promoting the proliferation
and suppressing the apoptosis of glioma cells through the JNK/MAPK signaling
pathway.
PMID- 26439037
TI - Ovarian transposition in young women and fertility sparing.
AB - OBJECTIVE: Ovarian transposition is a highly effective surgical procedure used to
preserve ovarian function in premenopausal patients with cancers requiring
postoperative or primary pelvic radiotherapy. Pelvic irradiation determines
severe damage of ovarian DNA and iatrogenic ovarian failure with premature
menopause, necessity of long-term hormone replacement therapy and infertility.
MATERIALS AND METHODS: We conducted an extensive research of the literature in
Medline between January 2000 and April 2015 using the key-words "ovarian
transposition radiotherapy", "radiotherapy gonadal function", radiotherapy
fertility sparing". The population included young women with normal ovarian
function affected by cancers that required pelvic radiotherapy. We have examined
32 articles reporting on 1189 women undergoing ovarian transposition. Median age
was 32.5 years, follow up was median 48 months. The procedure has been performed
in patients less than 40 years of age. Surgery has been achieved by laparotomy or
laparoscoy. We have analyzed effects of radiotherapy on ovarian function.
RESULTS: The proportion of women treated by ovarian transposition preserved
ovarian function was 70%. About 86% of patients did not develop ovarian cysts and
in 98-99% of cases did not occur any metastatic disease. CONCLUSIONS: Ovarian
transposition is associated with significant preservation of ovarian function and
a low frequency of complications as cysts and metastasis. In 31% of cases the
procedure can fail. Further studies are needed to evaluate the efficacy of
ovarian transposition and the follow up. Ovarian transposition should be
discussed at the time of cancer diagnosis in every premenopausal woman requiring
pelvic radiotherapy.
PMID- 26439038
TI - Alpha Lipoic Acid (ALA) effects on subchorionic hematoma: preliminary clinical
results.
AB - OBJECTIVE: The clinic use of alpha Lipoic Acid (ALA) is linked to its capability
to exert antioxidant effects and, more interestingly, to counteract the
pathologic changes of complex networks of cytokines, chemokines and growth
factors, restoring their physiological state. The aim of this randomized
controlled clinical trial was to test the contribution of oral supplementation of
ALA to the standard treatment with Progesterone vaginal suppositories, in healing
subchorionic hematomas in patients with threatened miscarriage. Controls were
administered only Progesterone suppositories. PATIENTS AND METHODS: Nineteen
pregnant women in the first trimester of gestation, with threatened miscarriage
and ultrasound evidence of subchorionic hematoma, were included in the trial and
randomly divided in two groups: controls, treated with 400 mg Progesterone (200
mg 2 times per day), given by vaginal suppositories, and case study treated with
the same Progesterone dosage, plus ALA, given orally at the dose of 600 mg (300
mg 2 times per day, DAV(r), Lo.Li. Pharma srl, Italy). Sixteen patients completed
the trial. Treatment was performed until complete resolution of the clinical
picture. RESULTS: In both groups, the subjects improved significantly but, in
general, a better and faster evolution in the major signs of threatened
miscarriage was observed in the subjects treated with ALA and Progesterone. In
these patients, the speed of resorption of subchorionic hematoma was
significantly (p <= 0.05) superior compared to controls. The ALA and Progesterone
group showed a faster decrease or disappearance of all symptoms than that
observed in the control group, however the difference was not significant.
CONCLUSIONS: These preliminary results suggest that ALA supplementation
significantly contributes to speed up the process of restoration of physiological
conditions in threatened miscarriage and ameliorates the medical conditions of
both the mothers and the foetus, probably modulating the networks of cytokines,
growth factors and other molecules.
PMID- 26439039
TI - Serum chitotriosidase levels in cancer patients undergoing high dose chemotherapy
and stem cell transplantation.
AB - OBJECTIVE: Human chitotriosidase (ChT) is an active chitinase expressed by
activated phagocytes. Increased ChT activity has been reported in systemic
Candida albicans infections and in Gram-negative and Gram-positive bacterial
infections, indicating that an increase in ChT activity reflects phagocyte
activation. The aim of this study was to determine the changes in serum ChT
activity in patients who underwent high dose chemotherapy (HDC) and stem cell
transplantation (SCT), who are at an increased risk for fungal and bacterial
infections due to depression of the immune system during the neutropenic period.
PATIENTS AND METHODS: A total of 55 SCT patients were included in the study.
Serum ChT activity was determined before the initiation of HDC and during the
neutropenic period after hematopoietic stem cell reinfusion on post-transplant
first, fifth and tenth days. RESULTS: Chitotriosidase levels before
transplantation were significantly lower than the results at first, fifth and
tenth days post-hematopoietic stem cell reinfusion. CONCLUSIONS: Although the
number of neutrophils was low, ChT enzyme activity was high in newly produced
granules of neutrophils. Chitotriosidase may be supplemented as a drug for
preventing and treating infections in the near future.
PMID- 26439040
TI - Effects of oleic acid on SP-B expression and release in A549 cells.
AB - OBJECTIVE: Pulmonary surfactant-associated protein B (SP-B), which is synthesized
and secreted by alveolar epithelial type II cells, is crucial for normal
functioning of pulmonary surfactant. Degeneration of pulmonary surfactant is the
essential cause of acute lung injury (ALI). ALI is often studied in animal models
using oleic acid, and the effects of oleic acid on pulmonary surfactant and SP-B
are not clear. In this study, we examined the effects of oleic acid on the A549
cell line which resembles the alveolar epithelial type II cells. MATERIALS AND
METHODS: A549 cells were exposed for 24 hours to 300, 400, 500 or 600 uM of oleic
acid. Cell morphological changes were observed using an inverted microscope, and
cell proliferation was quantified with the Cell Counting Kit-8. Extracellular SP
B levels were assessed by ELISA, whereas intracellular SP-B expression by Western
blot. RESULTS: Oleic acid caused dose-dependent changes in cell morphology of
A549 cells and decreased their proliferation. This was accompanied by release of
SP-B into extracellular supernatants and corresponding decrease of intracellular
levels of this protein. CONCLUSIONS: Oleic acid causes a dose-dependent injury to
A549 cells, release of SP-B into extracellular compartment, and decrease of
intracellular SP-B expression. Our findings provide mechanistic insights into
animal modeling of ALI with oleic acid.
PMID- 26439041
TI - The study of prevalence rate, and clinical characteristics of high altitude
deterioration.
AB - OBJECTIVE: This study was aimed to investigate the prevalence rate and clinical
characteristics of high altitude deterioration (HADT), which would provide a
scientific basis for the diagnosis and prevention of HADT. SUBJECTS AND METHODS:
A total of 175 subjects, who had migrated to a high altitude (4516 m) for more
than 1 year, were investigated. A questionnaire survey based on the symptoms of
HADT was conducted, and 117 subjects were determined to have HADT according to
the diagnostic criteria of HADT. To explore the clinical characteristics of HADT,
117 HADT patients and 31 healthy individuals were assigned to HADT patient group
and healthy control group, respectively. Their body mass indexes (BMIs), blood
rheology, full blood count (including hemoglobin concentration, leukocyte count,
neutrophil count, lymphocyte count and platelet count), blood pressure, heart
rate, oxygen saturation as well as left ventricular ejection fraction (LVEF) and
fraction shortening (LVFS) were assessed. RESULTS: The prevalence rate of HADT
was 66.9% at a high altitude of 4516 m. Compared with those in healthy people at
high altitude, some health indicators such as BMI, leukocyte count, neutrophil
count, lymphocyte count, platelet count, systolic blood pressure, oxygen
saturation, LVEF value and LVFS value were lower but other indicators including
the blood viscosity, hematocrit, hemoglobin concentration and heart rate were
higher in patients with HADT. CONCLUSIONS: The prevalence rate of HADT (66.9%)
was high among people moving to a high altitude of 4516 m. Clinical
characteristics of HADT were: (1) Impairment of left ventricular systolic
function; (2) Immune depression; (3) Microcirculation disturbance; and (4)
Decline of hemostasis and coagulation function.
PMID- 26439042
TI - Insulin sensitivity indices: fasting versus glucose-stimulated indices in
pediatric non-alcoholic fatty liver disease.
AB - OBJECTIVE: We aimed to compare insulin sensitivity indices, fasting vs glucose
stimulated, in children and adolescents with non-alcoholic fatty liver disease.
PATIENTS AND METHODS: Two hundred-eleven obese children with median age of 11.24
+/- 2.65 years were evaluated. After initial clinical and anthropometric
examination, B-mode ultrasonography (USG) was performed and all subjects
underwent Oral Glucose Tolerance Test (OGTT). Quantitative insulin sensitivity
check index (QUICKI), homeostatic model assessment for insulin resistance (Homa
IR), the insulinogenic index (IGI), the Matsuda index, and the oral glucose
insulin sensitivity (OGIS) model were used to determine peripheral insulin
sensitivity. RESULTS: 59.24% (68 boys, 57 girls) of obese children had NALFD. The
prevalence of FLD in obese adolescents was significantly higher than in
prepubertal children (65.8% vs. 51.5%). Fasting glucose, insulin, Homa-IR,
QUICKI, and OGIS and Matsuda were significantly different between subjects with
and without NALFD. Insulin and glucose indices were not found to be significantly
different in the prepubertal group, whereas Homa-IR, QUICKI, Matsuda, and OGIS
were significantly different in the pubertal group. Age, waist circumference, and
OUICKI were found to be risk factors associated with the presence of NALFD in the
logistic-regression analysis. CONCLUSIONS: Age, waist circumference, and OUICKI
were found to be risk factors associated with NALFD. As the value of QUICKI
decreases, the probability of having steatosis increases. Although OGTT results
gave the information about the glucose tolerance of a subject, indices derived
from OGTT were not found to be superior to the traditional surrogates such as
Homa-IR or QUICKI.
PMID- 26439043
TI - Correlation research on the protein expression (p75NTR, bax, bcl-2, and caspase
3) and cortical neuron apoptosis following mechanical injury in rat.
AB - OBJECTIVE: In this study, we aimed to survey the role of p75NTR, bax, bcl-2, and
caspase-3 in the progress of traumatic brain injury (TBI). MATERIALS AND METHODS:
A mechanical trauma model of vital neurons was established by putting external
pressure, contusion and centrifugal acceleration on neurons. Morphological
change, survival rate, assay of LDH activity, and apoptosis rate were evaluated
for mild, medium and severe injury models. The expression of bax, bcl-2, caspase
3, p75NTR, p75NTR mRNA was determined by immunohistochemistry,
immunofluorescence, Western blotting and RT-PCR. RESULTS: There was a transient
high level Bcl-2 protein within 2 h after injury to increase neuronal tolerance
and avoid apoptosis. Subsequently p75NTR, Bax/Bcl-2, and Caspase-3 reached their
peaks from 48 to 72 h accompanied with the maximum apoptosis rate. CONCLUSIONS:
Our results suggest that apoptosis ratio in varying degree injury groups are
correlated with the expression level of p75NTRmRNA, p75NTR, Caspase-3, Bax/Bcl-2
ratio.
PMID- 26439044
TI - A study on the protective role of doxycycline upon dopaminergic neuron of LPS-PD
rat model rat.
AB - OBJECTIVE: To investigate the protective role of doxycycline upon the
dopaminergic neuron of the lipopolysaccharide-Parkinson disease (LPS-PD) model
rat and its mechanism. MATERIALS AND METHODS: Animals were randomly divided into
three groups: normal control group, LPS group and doxycycline intervention.
Group; establishing The PD model was created by injecting LPS stereo-tactically
into the substantia nigra; observing the changes in the dopaminergic neurons and
the major histocompatibility complex II (MHC II) positive microglia before and
after the intervention of doxycycline with immunohistochemical staining. Using
the HPLC-ED (high performance liquid chromatography-electrochemical detector) to
test the changes in the striatal dopamine (DA), and DOPAC (dihydroxy phenyl
acetic acid) content; adopting Western blotting was adopted to test the
expression of the substantia nigra microglia MHC II (major histocompatibility
complex II) protein. RESULTS: After the intervention of doxycycline, in the LPS
group, the surviving dopamine neurons in the substantia nigra rose from 38% +/-
5% to 79% +/- 4% (p < 0.01); striatal DA and DOPAC content of the LPS group
increased from 4.89 +/- 0.27 and 0.70 +/- 0.07 to 7.00 +/- 0.34 and 1.10 +/- o.
10 respectively (p < 0.01). The average number of rotation induced
intraperitoneal injection of apomorphine of the animals in the LPS group reduced
from (208 +/- 14); time/30 min to (80 +/- 12) times/30 min (p < 0.01); while the
number of the MHC II positive cells in the substantia nigra pars compacta in the
LPS group reduced from 835 +/- 82 to 354 +/- 59 (p < 0.01); Western blotting of
the MHC II protein expression showed a significant reduction. CONCLUSIONS:
Doxycycline can inhibit degeneration of LPS-induced dopaminergic neurons. Its
neuroprotective function is achieved by downregulating the microglia MHC II
expression.
PMID- 26439045
TI - Evaluation of aqueductal CSF flow dynamics with phase contrast cine MR imaging in
idiopathic intracranial hypertension patients: preliminary results.
AB - OBJECTIVE: We aimed to evaluate dynamic cerebrospinal fluid (CSF) flow in
idiopathic intracranial hypertension (IIH) patients with new MRI technology phase
contrast cine (PCC) MRI. PATIENTS AND METHODS: Nineteen patients diagnosed with
idiopathic intracranial hypertension and 11 healthy volunteers were included in
this study. Nine of the IIH cases had been previously diagnosed and had been on
drug treatment and 10 cases were diagnosed with IIH recently and had not been put
on drug treatment yet. All CSF flow datas were evaluated by phase contrast-MRI
using a 1,5 T MRI. The CSF flow was calculated in the equidistant MRI sequence
which was taken through a cardiac cycle. RESULTS: Mean aqueduct area in the IIH
group was 3.04 +/- 1.14 mm2, mean peak rate was 3.29 +/- 1.77 cm/sec, mean
average rate was 0.35 +/- 0.33 cm/sec and mean flow was 0.67 +/- 0.95 ml/min. In
the control group mean aqueduct area was 2.87 +/- 1.01 mm2, mean peak rate was
4.20 +/- 1.40 cm/sec, mean average rate was 0.37 +/- 0.18 cm/sec and mean flow
was 0.64 +/- 0.40 ml/min. A statistically significant difference was found for
the PCC MRI parameter of mean rate value (p: 0.007) between the control group and
IIH patients. A statistically insignificant (p: 0.058) but marked difference was
found for mean flow value. CONCLUSIONS: To our knowledge this study is the first
CSF flow study in the idiopathic intracranial hypertension patients. We found a
difference between the IIH groups and controls in mean rate and flow parameters.
It was interesting that the mean rate and flow values of the untreated group that
were higher than the controls. CSF flow analysis may be a marker to follow up IIH
patients.
PMID- 26439046
TI - Study on the carotid atherosclerotic plaque of patients suffering from ischemic
cerebrovascular disease by 64 slices CT.
AB - OBJECTIVE: To explore the correlation between the features of a carotid plaque of
patients suffering from carotid atherosclerosis and ischemic cerebrovascular
disease by 64 slices computed tomography (CT). PATIENTS AND METHODS: One hundred
patients with carotid atherosclerosis were divided into the ischemic event group
(n=48) and non-ischemic event group (n=52). The features of the carotid plaque
were detected by 64 slices CT. RESULTS: One hundred and thirteen plaques were
found in the ischemic event group. The proportions of fatty, calcified, and mixed
plaque were 35.4%, 30.1%, and 34.5%. There are 78 plaques found in the non
ischemic event group. The proportions of fatty, calcified, and mixed plaque were
21.8%, 51.3%, and 26.9%. The distribution difference between the three types of
plaques was statistically significant (p<0.05). The proportions of mixed plaque
composed mainly of fatty plaque were 64.1% and 23.8%. These two constituent
ratios are significantly different from those of statistical processing (p<0.01).
There are 10 cases of plaque ulceration out of the 100 cases, among which eight
are from the ischemic event group and two cases from the other group. After
statistical processing, the incidence rates of plaque ulceration from these two
groups are significantly different (p<0.05). CONCLUSIONS: The 64 slices CT can
accurately present the morphological features of the carotid plaque. It indicates
that the fatty plaque, mixed plaque composed mainly of fatty plaque and
ulcerative plaque can cause ischemic cerebrovascular events.
PMID- 26439047
TI - A study on the susceptibility of allogeneic human hepatocytes to porcine
endogenous retrovirus.
AB - OBJECTIVE: Porcine endogenous retrovirus (PERV) is a virus that can be integrated
into porcine genome. It has been proved that PERV can infect the cells of a
variety of species. However, little is known about the infectivity of PERV to
human hepatocytes. The present study focused on the susceptibility of primary
human hepatocytes to PERV. MATERIALS AND METHODS: Cell culture supernatant
containing PERV was used to infect primary allogeneic hepatocytes and human
embryonic kidney cell line HEK-293. The integration of PERV into the genome and
PERV expression were detected by using PCR and RT-PCR. RESULTS: Gene and mRNA
sequences of PERV were detected in HEK-293 cells; however, viral gene expression
was not detected in 3 groups of primary allogeneic hepatocytes. CONCLUSIONS: HEK
293 cells can be infected by PERV, but 3 groups of primary allogeneic hepatocytes
were not sensitive to PERV, indicating PERV had no infectivity to primary human
hepatocytes.
PMID- 26439048
TI - Key factors of therapeutic effects for surgery in patients with cirrhotic portal
hypertension.
AB - OBJECTIVE: In the clinical management of cirrhotic portal hypertension, surgery
is often necessary; however, the operative mortality rate is high. PATIENTS AND
METHODS: Data from 161 patients, who underwent surgery for cirrhotic portal
hypertension, were analyzed, and 24 potential predictors of surgical outcome were
assessed. A Kruskal-Wallis rank sum test was used for single-factor comparisons,
and multivariate logistic regression for multifactor comparisons to identify key
factors for poor surgical outcomes and calculate their scores. RESULTS: Six
predictors of poor surgical outcomes were identified: postoperative bleeding
within 30 h of > 2 L, with a score of 3; severe liver atrophy (an anteroposterior
diameter of the left lobe of <= 55 mm and an oblique diameter of the right lobe
<= 110 mm), with a score of 3; a base excess of <-3 mmol/L, with a score of 3; a
platelet count of <3 T/L, with a score of 2; an amount of intraoperative bleeding
of > 2 L, with a score of 2; and a red blood cell count of < 3 G/L, with a score
of 1. For patients with good outcome (n = 147), all patients had a score of <= 3,
except one patient who had a score of 4. With respect to patients who died (n =
14), all had a score of >= 5, except one patient who had a score of 4. A
significant difference was observed between the two groups (p < 0.05). The
mortality was 100% in patients with a score of >= 7. CONCLUSIONS: Six key factors
for poor surgical outcomes were identified in this study. Operative mortality
appears to be significantly increased in patients with a score of 5-6. Surgery
should be contraindicated in patients with a score of >= 7. To reduce mortality,
close attention should be paid to preoperative and intraoperative treatment and
prevention to achieve a score of < 4.
PMID- 26439049
TI - A role of pre-mir-10a coding region variant in host susceptibility to coxsackie
virus-induced myocarditis.
AB - OBJECTIVE: Acute viral myocarditis (VM) is an important cause of sudden cardiac
death and heart failure in healthy young person. Direct virus-mediated injury and
secondary immune reactions, including inflammatory and autoimmune responses, have
been reported both in animal models and in humans. Recently, genetic variation
has been confirmed related to myocarditis process and susceptibility to VM. In
this study, we scanned 339bp of pri-miR-10a coding region in CVB3 VM patients,
want to found genetic relations between miR-10a and VM susceptibility. PATIENTS
AND METHODS: The secondary structure of two genotype 220 bp pri-miR-10a sequences
was predicted using RNAfold web server. In vitro biological functional study
concluded dual luciferase assay and Western blotting. RESULTS: We found the rare
allele T of rs3809783 was accumulated in VM patients and related to VM
significantly. Subsequently, we confirmed that ITCH, a NK-kappaB signaling
suppressor, is a direct target of miR-10a. In vitro biological functional study
indicated that this site variation reduced mature miR-10a expression and induced
a down-regulated cytokine secretion in the cell culture supernatant. CONCLUSIONS:
The results suggest that the rare allele T in pri-miR-10a coding region should be
involved in the CVB3 caused VM pathogenesis through weakening host anti-virus
immune response. This site may be used for clinical genetic evaluation for VM
susceptibility.
PMID- 26439050
TI - Two markers in predicting the cardiovascular events in patients with polycystic
ovary syndrome: increased P-wave and QT dispersion.
AB - OBJECTIVE: Polycystic ovary syndrome (PCOS) is a prevalent disease with many
potential long-term cardiovascular risks. P-wave dispersion (Pdis) and QT
dispersion (QTdis) have been shown to be noninvasive electrocardiographic
predictors for development of cardiac arrhythmias. In this study we aimed to
search Pdis and QTdis parameters in patients with PCOS. PATIENTS AND METHODS: The
study included 82 patients with PCOS and 74 age- and sex-matched healthy
controls. Baseline 12-lead electrocardiographic and transthoracic
echocardiographic measurements were evaluated. P-wave maximum duration (Pmax), P
wave minimum duration (Pmin), Pdis, QT interval, heart rate-corrected QT
dispersion and QTdis were calculated by two cardiologists. RESULTS: Patients wirh
PCOS had significantly higher QT dispersion (49.5 +/- 14.1 vs. 37.9 +/- 12.6 ms,
p < 0.001), and P wave dispersion (54.2 +/- 11.4 vs. 45.9 +/- 10.1 ms, p < 0.001)
than the controls. Serum testosterone and estradiol levels was correlated with
the Pdis (r = 0.677, p < 0.001 and r = 0.415, p < 0.001 respectively) and QTdis
(r = 0.326, p < 0.001 and r = 0.321, p < 0.001 respectively). CONCLUSIONS: Pdis
and QTdis are simple and useful electrocardiographic markers which may be used in
the prediction of the risk of adverse cardiovascular events in PCOS patients.
PMID- 26439051
TI - TRAM-34 attenuates hypoxia induced pulmonary artery smooth muscle cell
proliferation.
AB - OBJECTIVE: Hypoxia is an important risk factor for pulmonary arterial remodeling
in pulmonary arterial hypertension (PAH). Pulmonary artery smooth muscle cell
(PASMC) proliferation is a major contributor to pulmonary vascular remodeling.
The intermediate-conductance Ca2+-activated K+ channel (Kca3.1) has been
implicated in disease states characterized by excessive cell proliferation, but
its role in hypoxia-induced PASMC proliferation is unknown. In the present study,
we sought to investigate the effect of TRAM-34 (triarylmethane-34), a selective
blocker of Kca3.1, on hypoxia-induced PASMC proliferation and underlying
mechanisms. METHODS: PASMC was exposed to hypoxia (2% O2) for 24 hours, cell
proliferation and cell cycle analysis were measured by cell counting kit (CCK-8)
and flow cytometry. Cell signaling were examined using Quantitative real-time PCR
and Western blotting. RESULTS: CCK8 results showed that TRAM-34 reduced PASMC
proliferation under hypoxia. Flow cytometry revealed that TRAM-34 inhibited PASMC
proliferation by G0/G1 arrest. Quantitative real-time PCR and western blotting
results showed that Kca3.1 mRNA and protein levels were greater in PASMC after
hypoxia exposure for 24 hours. Elevated BMP2 (bone morphogenetic protein 2)
levels and decreased BMPR2/Smad1 signaling activation were also observed under
hypoxia, which were significantly attenuated by TRAM-34 intervention.
CONCLUSIONS: These results suggest that Kca3.1 inhibition with TRAM-34 inhibited
hypoxia-induced PASMC proliferation in the G0/G1 phase. The capability of TRAM-34
to increase BMPR2/p-Smad1 signaling may be part of the mechanisms for hypoxia
induced cell proliferation. Thus, our study implies that blockade of kca3.1 might
provide benefits to attenuating PAH vascular remodeling.
PMID- 26439052
TI - Comparison of propofol-remifentanil and propofol-ketamine combination for
dilatation and currettage: a randomized double blind prospective trial.
AB - OBJECTIVE: The purpose of this study was to compare the propofol-remifentanil
combination and propofol-ketamine combination for Dilatation and Curettage (DC)
procedure. PATIENTS AND METHODS: This prospective, double blind, and randomized
study comprised 81 female patients undergoing diagnostic DC. Patients were
randomly allocated to one of two groups; propofol-remifentanil (Group PR, n= 44)
or propofol-ketamine (Group PK, n= 37). The level of sedation was assessed with
the Ramsay Sedation Score (RSS). The patients' RSS scores were maintained at 4-5
with an additional 0.5 mg/kg bolus dose of propofol. Heart rate (HR), mean blood
pressure (MBP), peripheral oxygen saturation (SpO2), and RSS were recorded. The
Modify Aldrete Score (MAS) was used for postoperative recovery evaluation, and
the time to reach MAS score of 10 was recorded. Total dose of propofol, procedure
time, side effects, and satisfaction scores of patient and surgeon were also
recorded. RESULTS: The mean HR and MBP values of Group PR were lower than those
of Group PK, at all recording times. Sedation levels were significantly higher in
Group PK. The total dose of propofol consumed was significantly higher in Group
PR. The recovery time of Group PK was significantly longer than that of Group PF
(p<0.05). Nausea-vomiting and bradycardia were more frequent in the Group PR.
There was no difference in patient and surgeon satisfaction between the two
groups. CONCLUSIONS: Ketamine-propofol combination provides better hemodynamic
stability and better quality of sedation than propofol-remifentanil combination.
Ketamine still seems as an advantageous and safe drug for such procedure.
PMID- 26439053
TI - Oral misoprostol does not protect the kidneys from diclofenac induced toxicity:
data from an unilateral ureteral obstructive rat model.
AB - OBJECTIVE: Ureteral obstruction leads to permanent changes in the structure of
the kidney by several mechanisms. In this study, it was hypothesized that there
would be a protective effect of misoprostol against diclofenac in rats with
unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: Twenty-two female
rats were randomized into 5 groups of 4 and 2 rats for the control group. The
right ureter was sutured. The rats were grouped as control, contrast agent,
contrast agent +N-acetylcysteine (NAC), diclofenac and diclofenac + misoprostol
groups.Radiographic contrast agent was given iv on the 3rd day and other agents
were administered orally for 1 week. The rats were sacrified after 1 week and
histopathological and biochemical oxidative stress markers were evaluated.
RESULTS: The contrast agent and NAC group had lower rates of hemorrhage,
inflammation, obstructive dilatation and fatty degeneration compared to the
contrast agent only group (p < 0.05). No differences were seen in the normal
kidneys. Between all the groups, there was no difference for tubule epithelium
damage (p > 0.05). The contrast agent and NAC group had higher rates of
antioxidant SH level compared to the contrast agent only group (p < 0.05) and
lower rates of oxidative end product carbonyl groups (p < 0.05). For normal
kidneys no difference was seen. No statistical difference was seen in MDA levels
(p > 0.05). Statistically no difference was seen between the diclofenac group and
the diclofenac and misoprostol group neither pathologically nor chemically (p >
0.05). CONCLUSIONS: These results showed that NAC is protective against
radiographic contrast agent toxicity when given before and after administration
in obstructed kidneys as in previous data. Misoprostol was not observed to have
any protective effect against diclofenac in obstructed kidneys.
PMID- 26439054
TI - Three patients treated with daclatasvir and asunaprevir for recurrent hepatitis C
after liver transplantation: Case report.
AB - We previously reported our data on telaprevir or simeprevir used in combination
with pegylated interferon (PEG IFN) and ribavirin (RBV) for the treatment of
recurrent hepatitis C virus (HCV) genotype 1 infection after liver
transplantation (LT). Here, we report three patients who achieved viral responses
with no effect on the blood concentrations of immunosuppressive agents following
daclatasvir and asunaprevir treatment. The first patient was a 57-year-old man
with HCV-related liver cirrhosis who failed to respond to PEG IFN/RBV after
living donor LT. He had been treated with 1 mg/day of tacrolimus. The second was
a 63-year-old man with HCV-related liver cirrhosis and hepatocellular carcinoma
who failed to respond to PEG IFN/RBV after living donor LT. He had been treated
with 1 mg/day of tacrolimus. The third was a 61-year-old man with HCV-related
liver cirrhosis. He had been treated with mycophenolate mofetil (MMF). Serum HCV
RNA became undetectable by TaqMan polymerase chain reaction test after 4 weeks of
daclatasvir and asunaprevir treatment in all patients, and no remarkable
fluctuations in blood concentration were observed either in tacrolimus or in MMF
during 24 weeks of therapy. No adverse events were observed, and all patients
received the full dose of daclatasvir and asunaprevir over 24 weeks. Serum HCV
RNA remained negative at 12 weeks after the end of treatment in all patients. The
daclatasvir and asunaprevir treatment showed a remarkable viral response with
little effect on blood levels of immunosuppressive agents for recurrent HCV
genotype 1 infection after LT.
PMID- 26439055
TI - The influential child: How children affect their environment and influence their
own risk and resilience.
AB - Views regarding children's influence on their environment and their own
development have undergone considerable changes over the years. Following Bell's
(1968) seminal paper, the notion of children's influence and the view of
socialization as a bidirectional process have gradually gained wide acceptance.
However, empirical research implementing this theoretical advancement has lagged
behind. This Special Section compiles a collection of new empirical works
addressing multiple forms of influential child processes, with special attention
to their consequences for children's and others' positive functioning, risk and
resilience. By addressing a wide variety of child influences, this Special
Section seeks to advance integration of influential child processes into myriad
future studies on development and psychopathology and to promote the translation
of such work into preventive interventions.
PMID- 26439056
TI - Externalizing symptoms, effortful control, and intrusive parenting: A test of
bidirectional longitudinal relations during early childhood.
AB - At approximately 30, 42, and 54 months of age (N = 231), the relations among
children's externalizing symptoms, intrusive maternal parenting, and children's
effortful control (EC) were examined. Both intrusive parenting and low EC have
been related to psychopathology, but children's externalizing problems and low EC
might affect the quality of parenting and one another. Mothers' intrusive
behavior with their children was assessed with observations, children's EC was
measured with mothers' and caregivers' reports, and children's externalizing
symptoms were assessed with mothers', fathers', and caregivers' reports. In a
structural equation panel model, bidirectional relations between intrusive
parenting and EC were found: EC at 30 and 42 months predicted low levels of
intrusive parenting a year later, controlling for prior levels of parenting and
vice versa. Moreover, high levels of children's externalizing problems at both 30
and 42 months negatively predicted EC a year later, controlling for prior levels
of EC. Although externalizing problems positively predicted high EC over time,
this appeared to be a suppression effect because these variables had a strong
negative pattern in the zero-order correlations. Moreover, when controlling for
the stability of intrusive parenting, EC, and externalizing (all exhibited
significant stability across time) and the aforementioned cross-lagged predictive
paths, EC and externalizing problems were still negatively related within the 54
month assessment. The findings are consistent with the view that children's
externalizing behavior undermines their EC and contributes to intrusive mothering
and that relations between intrusive parenting and EC are bidirectional across
time. Thus, interventions that focus on modifying children's externalizing
problems (as well as the quality of parenting) might affect the quality of
parenting they receive and, hence, subsequent problems with adjustment.
PMID- 26439057
TI - The impact of children's internalizing and externalizing problems on parenting:
Transactional processes and reciprocal change over time.
AB - Most theoretical models of developmental psychopathology involve a transactional,
bidirectional relation between parenting and children's behavior problems. The
present study utilized a cross-lagged panel, multiple interval design to model
change in bidirectional relations between child and parent behavior across
successive developmental periods. Two major categories of child behavior
problems, internalizing and externalizing, and two aspects of parenting, positive
(use of support and structure) and harsh discipline (use of physical punishment),
were modeled across three time points spaced 3 years apart. Two successive
developmental intervals, from approximately age 7.5 to 10.5 and from 10.5 to
13.5, were included. Mother-child dyads (N = 138; 65 boys) from a lower income
longitudinal sample of families participated, with standardized measures of
mothers rating their own parenting behavior and teachers reporting on child's
behavior. Results revealed different types of reciprocal relations between
specific aspects of child and parent behavior, with internalizing problems
predicting an increase in positive parenting over time, which subsequently led to
a reduction in internalizing problems across the successive 3-year interval. In
contrast, externalizing predicted reduced levels of positive parenting in a
reciprocal sequence that extended across two successive intervals and predicted
increased levels of externalizing over time. Implications for prevention and
early intervention are discussed.
PMID- 26439059
TI - Mutual influences between child emotion regulation and parent-child reciprocity
support development across the first 10 years of life: Implications for
developmental psychopathology.
AB - Elucidating the mechanisms by which infant birth conditions shape development
across lengthy periods is critical for understanding typical and pathological
development and for targeted early interventions. This study examined how
newborns' regulatory capacities impact 10-year outcomes via the bidirectional
influences of child emotion regulation (ER) and reciprocal parenting across early
development. Guided by dynamic systems theory, 125 infants were tested at seven
time points: birth, 3, 6, 12, and 24 months and 5 and 10 years. Initial
regulatory conditions were measured by respiratory sinus arrhythmia (RSA; vagal
tone) and neurobehavioral regulation (Brazelton, 1973) at birth. At each
assessment between 3 months and 5 years, infant ER was microcoded from age
appropriate paradigms and mother-child reciprocity observed during social
interactions. Four regulation-related outcomes were measured at 10 years: child
RSA, empathy measured by mother-child conflict discussion and a lab paradigm,
accident proneness, and behavior problems. An autoregressive cross-lagged
structural model indicated that infant birth conditions impacted 10-year outcomes
via three mechanisms. First, child ER and reciprocal parenting were individually
stable across development and were each predicted by regulatory birth conditions,
describing gradual maturation of ER and reciprocity over time. Second, better ER
skills at one time point were related to greater reciprocity at the next time
point and vice versa, and these cross-time effects defined a field of individual
context mutual influences that mediated the links between neonatal RSA and 10
year outcomes. Third, direct associations emerged between neonatal regulation and
outcome, suggesting that birth conditions may establish a neurobiological milieu
that promotes a more mature and resilient system. These mechanisms describe
distinct "attractor" states that constrain the system's future options, emphasize
the importance of defining behavior-based phenotypes of heterotypic continuity,
and suggest that infants may shape their development by initiating unique
cascades of individual-context bidirectional effects.
PMID- 26439058
TI - (Positive) power to the child: The role of children's willing stance toward
parents in developmental cascades from toddler age to early preadolescence.
AB - In a change from the once-dominant view of children as passive in the parent-led
process of socialization, children are now seen as active agents who can
considerably influence that process. However, these newer perspectives typically
focus on the child's antagonistic influence, due either to a difficult
temperament or aversive, resistant, negative behaviors that elicit adversarial
responses from the parent and lead to future coercive cascades in the
relationship. Children's capacity to act as receptive, willing, even
enthusiastic, active socialization agents is largely overlooked. Informed by
attachment theory and other relational perspectives, we depict children as able
to adopt an active willing stance and to exert robust positive influence in the
mutually cooperative socialization enterprise. A longitudinal study of 100
community families (mothers, fathers, and children) demonstrates that willing
stance (a) is a latent construct, observable in diverse parent-child contexts,
parallel at 38, 52, and 67 months and longitudinally stable; (b) originates
within an early secure parent-child relationship at 25 months; and (c) promotes a
positive future cascade toward adaptive outcomes at age 10. The outcomes include
the parent's observed and child-reported positive, responsive behavior, as well
as child-reported internal obligation to obey the parent and parent-reported low
level of child behavior problems. The construct of willing stance has
implications for basic research in typical socialization and in developmental
psychopathology as well as for prevention and intervention.
PMID- 26439061
TI - Stability and change in resolution of diagnosis among parents of children with
autism spectrum disorder: Child and parental contributions.
AB - The contribution of change over time in parent and child characteristics to
parents' resolution of child's diagnosis was examined among 78 mothers and
fathers of children with autism spectrum disorder. Children's characteristics
(e.g., mental age and severity of symptoms), parental characteristics (e.g.,
attachment-related anxiety and stress level), and parents' resolution of their
child's diagnosis (resolved vs. unresolved) were examined at Time 1, and
reassessed 3 years later at Time 2. Results indicated a deferential contribution
of change in parent and child characteristics among mothers and fathers. An
increase in child symptom severity and in maternal attachment-related anxiety, as
well as longer durations of time since receiving the diagnosis, significantly
predicted maternal resolved status at Time 2. Conversely, none of the changes in
children's or paternal characteristics predicted paternal resolved status at Time
2. Results are discussed in relation to child and parental contributions to
resolution, the differences in the adjustment and well-being of mothers and
fathers of children with autism spectrum disorder, parental growth following
receiving the diagnosis, and the need for intervention components specific to
parental resolution and attachment-related anxiety.
PMID- 26439062
TI - Child effects and child care: Implications for risk and adjustment.
AB - Evocative effects of child characteristics on the quality and quantity of child
care were assessed in two studies using longitudinal data from the NICHD Study of
Early Child Care. We focus on the influence of child characteristics on two
important aspects of the child care experience: language stimulation provided by
caregivers and quantity of care. In Study 1, associations between the
developmental status of children aged 15 to 54 months and the language
stimulation provided by their caregivers were examined using path models, and
longitudinal child effects were detected across the earliest time points of the
study. In Study 2, the associations among child behavior, temperament,
development, and time in care were examined. Little evidence was found for such
child effects on time in care. The results are discussed in terms of the effects
of child care on child development and implications for developmental processes,
particularly for children at greatest risk for developmental delay or
psychopathology.
PMID- 26439063
TI - Violent peer influence: The roles of self-esteem and psychopathic traits.
AB - Evidence for the risks of psychopathic personality traits for adolescent
antisocial behavior are well documented in the literature. Little is known,
however, about who the peers of adolescents with these traits are and to what
extent they influence one another. In the current study, three dimensions of
psychopathic traits were distinguished: grandiose-manipulative traits, callous
unemotional traits, and impulsive-irresponsible traits. A dynamic social network
approach was used with three waves of longitudinal data from 1,772 adolescents
(51.1% girls, M age = 13.03 at first measurement). Results showed that
adolescents with grandiose-manipulative and callous-unemotional traits formed
peer relationships with adolescents who had low self-esteem. Furthermore, peers'
violence predicted stronger increases in violence for adolescents with low self
esteem than for other adolescents, and peers' violence predicted stronger
increases in adolescent violence for peers with high psychopathic traits than for
other peers. Thus, findings indicate that adolescents with low self-esteem are
vulnerable to deviant peer influence from peers with psychopathic traits.
PMID- 26439060
TI - Adolescents', mothers', and fathers' gendered coping strategies during conflict:
Youth and parent influences on conflict resolution and psychopathology.
AB - We observed gendered coping strategies and conflict resolution outcomes used by
adolescents and parents during a conflict discussion task to evaluate
associations with current and later adolescent psychopathology. We studied 137
middle- to upper-middle-class, predominantly Caucasian families of adolescents
(aged 11-16 years, 65 males) who represented a range of psychological
functioning, including normative, subclinical, and clinical levels of problems.
Adolescent coping strategies played key roles both in the extent to which parent
adolescent dyads resolved conflict and in the trajectory of psychopathology
symptom severity over a 2-year period. Gender-prototypic adaptive coping
strategies were observed in parents but not youth, (i.e., more problem solving by
fathers than mothers and more regulated emotion-focused coping by mothers than
fathers). Youth-mother dyads more often achieved full resolution of conflict than
youth-father dyads. There were generally not bidirectional effects among youth
and parents' coping across the discussion except boys' initial use of
angry/hostile coping predicted fathers' angry/hostile coping. The child was more
influential than the parent on conflict resolution. This extended to
exacerbation/alleviation of psychopathology over 2 years: higher conflict
resolution mediated the association of adolescents' use of problem-focused coping
with decreases in symptom severity over time. Lower conflict resolution mediated
the association of adolescents' use of angry/hostile emotion coping with
increases in symptom severity over time. Implications of findings are considered
within a broadened context of the nature of coping and conflict resolution in
youth-parent interactions, as well as on how these processes impact youth well
being and dysfunction over time.
PMID- 26439064
TI - Temperament and peer problems from early to middle childhood: Gene-environment
correlations with negative emotionality and sociability.
AB - Based in a transactional framework in which children's own characteristics and
the social environment influence each other to produce individual differences in
social adjustment, we investigated relationships between children's peer problems
and their temperamental characteristics, using a longitudinal and genetically
informed study of 939 pairs of Israeli twins followed from early to middle
childhood (ages 3, 5, and 6.5). Peer problems were moderately stable within
children over time, such that children who appeared to have more peer problems at
age 3 tended to have also more peer problems at age 6.5. Children's temperament
accounted for 10%-22% of the variance in their peer problems measured at the same
age and for 2%-7% of the variance longitudinally. It is important that genetic
factors accounted for the association between temperament and peer problems and
were in line with a gene-environment correlation process, providing support for
the proposal that biologically predisposed characteristics, particularly negative
emotionality and sociability, have an influence on children's early experiences
of peer problems. The results highlight the need for early and continuous
interventions that are specifically tailored to address the interpersonal
difficulties of children with particular temperamental profiles.
PMID- 26439065
TI - Social and economic antecedents and consequences of adolescent aggressive
personality: Predictions from the interactionist model.
AB - The present study examined the development of a cohort of 279 early adolescents
(52% female) from 1990 to 2005. Guided by the interactionist model of
socioeconomic status and human development, we proposed that parent aggressive
personality, economic circumstances, interparental conflict, and parenting
characteristics would affect the development of adolescent aggressive personality
traits. In turn, we hypothesized that adolescent aggressiveness would have a
negative influence on adolescent functioning as an adult in terms of economic
success, personality development, and close relationships 11 years later.
Findings were generally supportive of the interactionist model proposition that
social and economic difficulties in the family of origin intensify risk for
adolescent aggressive personality (the social causation hypothesis) and that this
personality trait impairs successful transition to adult roles (the social
selection hypothesis) in a transactional process over time and generations. These
results underscore how early development leads to child influences that appear to
directly hamper the successful transition to adult roles (statistical main
effects) and also amplify the negative impact of dysfunctional family systems on
the transition to adulthood (statistical interaction effects). The findings
suggest several possible points of intervention that might help to disrupt this
negative developmental sequence of events.
PMID- 26439066
TI - Take your mind off it: Coping style, serotonin transporter linked polymorphic
region genotype (5-HTTLPR), and children's internalizing and externalizing
problems.
AB - Individuals with the short variant of the serotonin transporter linked
polymorphic region gene are more susceptible than individuals homozygous for the
long allele to the effects of stressful life events on risk for internalizing and
externalizing problems. We tested whether individual differences in coping style
explained this increased risk for problem behavior among youth who were at both
genetic and environmental risk. Participants included 279 children, ages 8-11,
from the Children's Experiences and Development Study. Caregivers and teachers
reported on children's internalizing and externalizing symptoms, and caregivers
and children on children's exposure to harsh parenting and parental warmth in
middle childhood, and traumatic events. Children reported how frequently they
used various coping strategies. Results revealed that short/short homozygotes had
higher levels of internalizing problems compared with long allele carriers and
that short allele carriers had higher levels of externalizing problems compared
with long/long homozygotes under conditions of high cumulative risk. Moreover,
among children who were homozygous for the short allele, those who had more
cumulative risk indicators less frequently used distraction coping strategies,
which partly explained why they had higher levels of internalizing problems.
Coping strategies did not significantly mediate Gene * Environment effects on
externalizing symptoms.
PMID- 26439068
TI - Emergent patterns of risk for psychopathology: The influence of infant avoidance
and maternal caregiving on trajectories of social reticence.
AB - The current study investigated the influential role of infant avoidance on links
between maternal caregiving behavior and trajectories at risk for
psychopathology. A sample of 153 children, selected for temperamental reactivity
to novelty, was followed from infancy through early childhood. At 9 months,
infant avoidance of fear-eliciting stimuli in the laboratory and maternal
sensitivity at home were assessed. At 36 months, maternal gentle discipline was
assessed at home. Children were repeatedly observed in the lab with an unfamiliar
peer across early childhood. A latent class growth analysis yielded three
longitudinal risk trajectories of social reticence behavior: a high-stable
trajectory, a high-decreasing trajectory, and a low-increasing trajectory. For
infants displaying greater avoidance, 9-month maternal sensitivity and 36-month
maternal gentle discipline were both positively associated with membership in the
high-stable social reticence trajectory, compared to the high-decreasing social
reticence trajectory. For infants displaying lower avoidance, maternal
sensitivity was positively associated with membership in the high-decreasing
social reticence trajectory, compared to the low-increasing trajectory. Maternal
sensitivity was positively associated with the high-stable social reticence
trajectory when maternal gentle discipline was lower. These results illustrate
the complex interplay of infant and maternal behavior in early childhood
trajectories at risk for emerging psychopathology.
PMID- 26439069
TI - Child fear reactivity and sex as moderators of links between parenting and
preschool behavior problems.
AB - Reduced supportive parenting and elevated negative parenting behaviors increase
risks for maladaptive social adjustment during early childhood (e.g., Campbell,
Shaw, & Gilliom, 2000). However, the magnitude of these risks may vary according
to children's individual characteristics, such as sex and temperament. The
current study examines whether children's sex and fear reactivity moderate the
associations between mothers' observed parenting and children's behavior problems
1 year later. The sample consists of 151 predominantly African American, low
income families with one sibling who is approximately 2 years old and the closest
aged older sibling who is approximately 4 years old. Results from fixed-effects
within-family models indicate that fear distress (i.e., fearfulness) moderated
associations between mothers' observed negative parenting and children's
increased behavior problems, such that only those children with mean or higher
observed fear distress scores showed increased behavior problems when exposed to
mother's negative parenting. Child sex moderated associations between fear
approach reactivity (i.e., fearlessness) and mothers' observed supportive
parenting. Specifically, low fear approach combined with supportive parenting was
associated with fewer behavior problems for boys only. Implications of these
findings for preventive intervention are discussed.
PMID- 26439070
TI - Infant negative reactivity defines the effects of parent-child synchrony on
physiological and behavioral regulation of social stress.
AB - How infants shape their own development has puzzled developmentalists for
decades. Recent models suggest that infant dispositions, particularly negative
reactivity and regulation, affect outcome by determining the extent of parental
effects. Here, we used a microanalytic experimental approach and proposed that
infants with varying levels of negative reactivity will be differentially
impacted by parent-infant synchrony in predicting physiological and behavioral
regulation of increasing social stress during an experimental paradigm. One
hundred and twenty-two mother-infant dyads (4-6 months) were observed in the face
to-face still face (SF) paradigm and randomly assigned to three experimental
conditions: SF with touch, standard SF, and SF with arms' restraint. Mother
infant synchrony and infant negative reactivity were observed at baseline, and
three mechanisms of behavior regulation were microcoded; distress, disengagement,
and social regulation. Respiratory sinus arrhythmia baseline, reactivity, and
recovery were quantified. Structural equation modeling provided support for our
hypothesis. For physiological regulation, infants high in negative reactivity
receiving high mother-infant synchrony showed greater vagal withdrawal, which in
turn predicted comparable levels of vagal recovery to that of nonreactive
infants. In behavioral regulation, only infants low in negative reactivity who
received high synchrony were able to regulate stress by employing social
engagement cues during the SF phase. Distress was reduced only among calm infants
to highly synchronous mothers, and disengagement was lowest among highly reactive
infants experiencing high mother-infant synchrony. Findings chart two pathways by
which synchrony may bolster regulation in infants of high and low reactivity.
Among low reactive infants, synchrony builds a social repertoire for handling
interpersonal stress, whereas in highly reactive infants, it constructs a
platform for repeated reparation of momentary interactive "failures" and reduces
the natural tendency of stressed infants to disengage from source of distress.
Implications for the construction of synchrony-focused interventions targeting
infants of varying dispositions are discussed.
PMID- 26439067
TI - The interplay of birth weight, dopamine receptor D4 gene (DRD4), and early
maternal care in the prediction of disorganized attachment at 36 months of age.
AB - Disorganized attachment is an important early risk factor for socioemotional
problems throughout childhood and into adulthood. Prevailing models of the
etiology of disorganized attachment emphasize the role of highly dysfunctional
parenting, to the exclusion of complex models examining the interplay of child
and parental factors. Decades of research have established that extreme child
birth weight may have long-term effects on developmental processes. These effects
are typically negative, but this is not always the case. Recent studies have also
identified the dopamine D4 receptor (DRD4) as a moderator of childrearing effects
on the development of disorganized attachment. However, there are inconsistent
findings concerning which variant of the polymorphism (seven-repeat long-form
allele or non-seven-repeat short-form allele) is most likely to interact with
caregiving in predicting disorganized versus organized attachment. In this study,
we examined possible two- and three-way interactions and child DRD4 polymorphisms
and birth weight and maternal caregiving at age 6 months in longitudinally
predicting attachment disorganization at 36 months. Our sample is from the
Maternal Adversity, Vulnerability and Neurodevelopment project, a sample of 650
mother-child dyads. Birth weight was cross-referenced with normative data to
calculate birth weight percentile. Infant DRD4 was obtained with buccal swabs and
categorized according to the presence of the putative allele seven repeat.
Macroanalytic and microanalytic measures of maternal behavior were extracted from
a videotaped session of 20 min of nonfeeding interaction followed by a 10-min
divided attention maternal task at 6 months. Attachment was assessed at 36 months
using the Strange Situation procedure, and categorized into disorganized
attachment and others. The results indicated that a main effect for DRD4 and a
two-way interaction of birth weight and 6-month maternal attention (frequency of
maternal looking away behavior) and sensitivity predicted disorganized attachment
in robust logistic regression models adjusted for social demographic covariates.
Specifically, children in the midrange of birth weight were more likely to
develop a disorganized attachment when exposed to less attentive maternal care.
However, the association reversed with extreme birth weight (low and high). The
DRD4 seven-repeat allele was associated with less disorganized attachment
(protective), while non-seven-repeat children were more likely to be classified
as disorganized attachment. The implications for understanding inconsistencies in
the literature about which DRD4 genotype is the risk direction are also
considered. Suggestions for intervention with families with infants at different
levels of biological risk and caregiving risk are also discussed.
PMID- 26439071
TI - The association of temperament and maternal empathy with individual differences
in infants' neural responses to emotional body expressions.
AB - We examined the role of infant temperament and maternal dispositional empathy in
the neural processing of happy and fearful emotional body expressions in 8-month
old infants by measuring event-related brain potentials. Our results revealed
that infants' tendency to approach novel objects and people was positively
correlated with the neural sensitivity (attention allocation) to fearful
expressions, while infant fearfulness was negatively correlated to the neural
sensitivity to fearful expressions. Maternal empathic concern was associated with
infants' neural discrimination between happy and fearful expression, with infants
of more empathetically concerned mothers showing greater neural sensitivity
(attention allocation) to fearful compared to happy expressions. It is critical
that our results also revealed that individual differences in the sensitivity to
emotional information are explained by an interaction between infant temperament
and maternal empathic concern. Specifically, maternal empathy appears to impact
infants' neural responses to emotional body expressions, depending on infant
fearfulness. These findings support the notion that the way in which infants
respond to emotional signals in the environment is fundamentally linked to their
temperament and maternal empathic traits. This adds an early developmental
neuroscience dimension to existing accounts of social-emotional functioning,
suggesting a complex and integrative picture of why and how infants' emotional
sensitivity varies.
PMID- 26439072
TI - Emerging psychopathology moderates upward social mobility: The intergenerational
(dis)continuity of socioeconomic status.
AB - Socioeconomic status (SES) is relatively stable across generations, but social
policies may create opportunities for upward social mobility among disadvantaged
populations during periods of economic growth. With respect to expanded
educational opportunities that occurred in Quebec (Canada) during the 1960s, we
hypothesized that children's social and academic competence would promote upward
mobility, whereas aggression and social withdrawal would have the opposite
effect. Out of 4,109 children attending low-SES schools in 1976-1978, a
representative subsample of 503 participants were followed until midadulthood.
Path analyses revealed that parents' SES predicted offspring's SES through
associations with offspring's likeability, academic competence, and educational
attainment. Interaction effects revealed individual risk factors that moderated
children's ability to take advantage of intrafamilial or extrafamilial
opportunities that could enhance their educational attainment. Highly aggressive
participants and those presenting low academic achievement were unable to gain
advantage from having highly educated parents. They reached lower educational
attainment than their less aggressive or higher achieving peers who came from a
similarly advantaged family background. Growing up with parents occupying low
prestige jobs put withdrawn boys and outgoing girls at risk for low educational
attainment. In conclusion, social policies can raise SES across generations, with
great benefits for the most disadvantaged segments of the population. However,
children presenting with emerging psychopathology or academic weaknesses do not
benefit from these policies as much as others, and should receive additional,
targeted services.
PMID- 26439073
TI - The effects of violence exposure on the development of impulse control and future
orientation across adolescence and early adulthood: Time-specific and generalized
effects in a sample of juvenile offenders.
AB - Impulse control and future orientation increase across adolescence, but little is
known about how contextual factors shape the development of these capacities. The
present study investigates how stress exposure, operationalized as exposure to
violence, alters the developmental pattern of impulse control and future
orientation across adolescence and early adulthood. In a sample of 1,354 serious
juvenile offenders, higher exposure to violence was associated with lower levels
of future orientation at age 15 and suppressed development of future orientation
from ages 15 to 25. Increases in witnessing violence or victimization were linked
to declines in impulse control 1 year later, but only during adolescence. Thus,
beyond previous experiences of exposure to violence, witnessing violence and
victimization during adolescence conveys unique risk for suppressed development
of self-regulation.
PMID- 26439074
TI - The stability of the feedback negativity and its relationship with depression
during childhood and adolescence.
AB - Feedback negativity (FN) is an event-related potential elicited by monetary
reward and loss; it is thought to relate to reward-related neural activity and
has been linked to depression in children and adults. In the current study, we
examined the stability of FN, and its relationship with depression in
adolescents, over 2 years in 45 8- to 13-year-old children. From Time 1 to Time
2, FN in response to monetary loss and in response to monetary gain showed
moderate to strong reliability (rs = .64 and .67, respectively); these
relationships remained significant even when accounting for related variables. FN
also demonstrated high within-session reliability. Moreover, the relationship
between a blunted FN and greater depression observed at Time 1 was reproduced at
Time 2, and the magnitude of FN at Time 1 predicted depressive symptomatology at
Time 2. These findings are consistent with the hypothesis that FN and its
relationship with depression remain consistent over the course of development,
and that FN may prospectively predict later depressive symptomatology. The
current results suggest that FN may be suitable as a biomarker of depressive
symptoms during adolescence.
PMID- 26439075
TI - Identifying early pathways of risk and resilience: The codevelopment of
internalizing and externalizing symptoms and the role of harsh parenting.
AB - Psychological disorders co-occur often in children, but little has been done to
document the types of conjoint pathways internalizing and externalizing symptoms
may take from the crucial early period of toddlerhood or how harsh parenting may
overlap with early symptom codevelopment. To examine symptom codevelopment
trajectories, we identified latent classes of individuals based on internalizing
and externalizing symptoms across ages 3-9 and found three symptom codevelopment
classes: normative symptoms (low), severe-decreasing symptoms (initially high but
rapidly declining), and severe symptoms (high) trajectories. Next, joint models
examined how parenting trajectories overlapped with internalizing and
externalizing symptom trajectories. These trajectory classes demonstrated that,
normatively, harsh parenting increased after toddlerhood, but the severe symptoms
class was characterized by a higher level and a steeper increase in harsh
parenting and the severe-decreasing class by high, stable harsh parenting. In
addition, a transactional model examined the bidirectional relationships among
internalizing and externalizing symptoms and harsh parenting because they may
cascade over time in this early period. Harsh parenting uniquely contributed to
externalizing symptoms, controlling for internalizing symptoms, but not vice
versa. In addition, internalizing symptoms appeared to be a mechanism by which
externalizing symptoms increase. Results highlight the importance of accounting
for both internalizing and externalizing symptoms from an early age to understand
risk for developing psychopathology and the role harsh parenting plays in
influencing these trajectories.
PMID- 26439076
TI - Genetic covariance between psychopathic traits and anticipatory skin conductance
responses to threat: Evidence for a potential endophenotype.
AB - The genetic architecture of the association between psychopathic traits and
reduced skin conductance responses (SCRs) is poorly understood. By using 752
twins aged 9-10 years, this study investigated the heritability of two SCR
measures (anticipatory SCRs to impending aversive stimuli and unconditioned SCRs
to the aversive stimuli themselves) in a countdown task. The study also
investigated the genetic and environmental sources of the covariance between
these SCR measures and two psychopathic personality traits:
impulsive/disinhibited (reflecting impulsive-antisocial tendencies) and
manipulative/deceitful (reflecting the affective-interpersonal features). For
anticipatory SCRs, 27%, 14%, and 59% of the variation was due to genetic, shared
environmental, and nonshared environmental effects, respectively, while the
percentages for unconditioned SCRs were 44%, 2%, and 54%. The
manipulative/deceitful (not impulsive/disinhibited) traits were negatively
associated with both anticipatory SCRs (r = -.14, p < .05) and unconditioned SCRs
(r = -.17, p < .05) in males only, with the former association significantly
accounted for by genetic influences (r g = -.72). Reduced anticipatory SCRs
represent a candidate endophenotype for the affective-interpersonal facets of
psychopathic traits in males.
PMID- 26439078
TI - Pubertal maturation and affective symptoms in adolescence and adulthood: Evidence
from a prospective birth cohort.
AB - The higher prevalence of affective symptoms among women compared to men emerges
in adolescence, and it has been associated with pubertal maturation. However, it
remains unclear whether pubertal timing has long-term influences on affective
symptoms. Using data from the British 1946 birth cohort, we investigated whether
pubertal timing was associated with affective symptoms over the life course,
distinguishing those with symptoms in adolescence only, symptoms in adulthood
only, and symptoms in both adolescence and adulthood. In females, there was no
evidence that early pubertal maturation was a risk factor for affective symptoms.
However, those with particularly late menarche (>=15 years) showed a lower risk
of adult-onset affective symptoms (odds ratio = 0.54, 95% confidence interval =
0.31, 0.95). This effect of late pubertal timing was not explained by a range of
sociobehavioral factors. In contrast, in males, late pubertal timing was
associated with increased risk of adolescent-onset affective symptoms that
tracked into adulthood (odds ratio = 2.10, 95% confidence interval = 1.44, 3.06).
This effect was partly explained by low prepubertal body mass index. Sex-specific
effects of pubertal timing on the long-term risk of affective symptoms might be
due to different effects of gonadal hormonal on the central nervous system, as
well as different social experiences during puberty.
PMID- 26439077
TI - Childhood dyspraxia predicts adult-onset nonaffective-psychosis-spectrum
disorder.
AB - Several neurological variables have been investigated as premorbid biomarkers of
vulnerability for schizophrenia and other related disorders. The current study
examined whether childhood dyspraxia predicted later adult nonaffective-psychosis
spectrum disorders. From a standardized neurological examination performed with
children (aged 10-13) at genetic high risk of schizophrenia and controls, several
measures of dyspraxia were used to create a scale composed of face/head
dyspraxia, oral articulation, ideomotor dyspraxia (clumsiness), and dressing
dyspraxia (n = 244). Multinomial logistic regression showed higher scores on the
dyspraxia scale predict nonaffective-psychosis-spectrum disorders relative to
other psychiatric disorders and no mental illness outcomes, even after
controlling for genetic risk, chi2 (4, 244) = 18.61, p < .001. Findings that
symptoms of dyspraxia in childhood (reflecting abnormalities spanning
functionally distinct brain networks) specifically predict adult nonaffective
psychosis-spectrum disorders are consistent with a theory of abnormal
connectivity, and they highlight a marked early-stage vulnerability in the
pathophysiology of nonaffective-psychosis-spectrum disorders.
PMID- 26439079
TI - Variability in diurnal testosterone, exposure to violence, and antisocial
behavior in young adolescents.
AB - The purpose of this report is to provide evidence of an association between
within-person variability in diurnal testosterone over 1 year, lifetime exposure
to violence, and the manifestation of antisocial behavior in 135 pubertal-aged
adolescents across 1 year. Adolescents' sex and lifetime history of violence
exposure moderated the association between within-person variability in diurnal
testosterone and antisocial behavior. Furthermore, sex-stratified analyses
revealed that lifetime history of exposure to violence moderated the association
between within-person variability in diurnal testosterone and antisocial behavior
in females only. This report is unique in that it illuminates sex differences in
within-person associations among exposure to violence, individual variability in
diurnal testosterone, and antisocial behavior.
PMID- 26439081
TI - The emergence of co-occurring adolescent polysubstance use and depressive
symptoms: A latent growth modeling approach.
AB - This study tests competing models of the relation between depression and
polysubstance use over the course of adolescence. Participants included a
nationwide sample of adolescents (N = 3,604), ages 12 to 17 at study Wave 1,
assessed annually for 3 years. Models were tested using cohort-sequential latent
growth curve modeling to determine whether depressive symptoms at baseline
predicted concurrent and age-related changes in drug use, whether drug use at
baseline predicted concurrent and age-related changes in depressive symptoms, and
whether initial levels of depression predicted changes in substance use
significantly better than vice versa. The results suggest a transactional model
such that early polysubstance use promotes early depressive symptoms, which in
turn convey elevated risk for increasing polysubstance use over time, which in
turn conveys additional risk for future depressive symptoms, even after
accounting for gender, ethnicity, and household income. In contrast, early drug
use did not portend risk for future depressive symptoms. These findings suggest a
complicated pattern of interrelations over time and indicate that many current
models of co-occurring polysubstance use and depressive symptoms may not fully
account for these associations. Instead, the results suggest a developmental
cascade, in which symptoms of one disorder promote symptoms of the other across
intrapersonal domains.
PMID- 26439082
TI - Synthesis and O2 Reactivity of a Titanium(III) Metal-Organic Framework.
AB - Metal-organic frameworks featuring pores lined with exposed metal cations have
received attention for a wide range of adsorption-related applications. While
many frameworks with coordinatively unsaturated M(II) centers have been reported,
there are relatively few examples of porous materials with coordinatively
unsaturated M(III) centers. Here, we report the synthesis and characterization of
Ti3O(OEt)(bdc)3(solv)2 (Ti-MIL-101; bdc(2-) = 1,4-benzenedicarboxylate; solv =
N,N-dimethylformamide, tetrahydrofuran), the first metal-organic framework
containing exclusively Ti(III) centers. Through a combination of gas adsorption,
X-ray diffraction, magnetic susceptibility, and electronic and vibrational
spectroscopy measurements, this high-surface-area framework is shown to contain
five-coordinate Ti(III) centers upon desolvation, which irreversibly bind O2 to
form titanium(IV) superoxo and peroxo species. Electronic absorption spectra
suggest that the five-coordinate Ti(III) sites adopt a distorted trigonal
bipyramidal geometry that effectively shields nuclear charge and inhibits strong
adsorption of nonredox-active gases.
PMID- 26439080
TI - Emotion-based preventive intervention: Effectively promoting emotion knowledge
and adaptive behavior among at-risk preschoolers.
AB - Effectiveness studies of preschool social-emotional programs are needed in low
income, diverse populations to help promote the well-being of at-risk children.
Following an initial program efficacy study 2 years prior, 248 culturally diverse
Head Start preschool children participated in the current effectiveness trial and
received either the Emotion-Based Prevention Program (EBP) or the I Can Problem
Solve (ICPS) intervention. Pre- and postdata collection included direct child
assessment, teacher report, parent interview, and independent observations.
Teachers implementing the EBP intervention demonstrated good and consistent
fidelity to the program. Overall, children in EBP classrooms gained more emotion
knowledge and displayed greater decreases in negative emotion expressions and
internalizing behaviors across the implementation period as compared to children
in ICPS classrooms. In addition, cumulative risk, parental depressive symptoms,
and classroom climate significantly moderated treatment effects. For children
experiencing more stress or less support, EBP produced more successful outcomes
than did ICPS. These results provide evidence of EBP sustainability and program
effectiveness, as did previous findings that demonstrated EBP improvements in
emotion knowledge, regulation skills, and behavior problems replicated under
unsupervised program conditions.
PMID- 26439083
TI - Multiple glacial refugia for cool-temperate deciduous trees in northern East
Asia: the Mongolian oak as a case study.
AB - In East Asia, temperate forests are predicted to have retracted southward to c.
30 degrees N during the last glacial maximum (LGM) based on fossil pollen data,
whereas phylogeographic studies have often suggested glacial in situ survival of
cool-temperate deciduous trees in their modern northern ranges. Here we report a
study of the genetic diversity and structure of 29 natural Mongolian oak (Quercus
mongolica) populations using 19 nuclear simple sequence repeat (nSSR) loci and
four chloroplast DNA fragments. Bayesian clustering analysis with nSSRs revealed
five groups, which were inferred by approximate Bayesian computation (ABC) to
have diverged in multiple refugia through multiple glacial-interglacial cycles.
Analysis of chloroplast DNA variation revealed four lineages that were largely
but incompletely geographically disjunct. Ecological niche modelling (ENMs)
indicated a southward range shift of the oak's distribution at the LGM, although
high suitability scores were also evident in the Changbai Mts. (Northeast China),
the Korean Peninsula, areas surrounding the Bohai Sea, and along the coast of the
Russian Far East. In addition, endemic chloroplast DNA haplotypes and nuclear
lineages occurred in high-latitude northern areas where the ENM predicted no
suitable habitat. The combined evidence from nuclear and chloroplast DNA, and the
results of the ENM clearly demonstrate that multiple northern refugia, including
cryptic ones, were maintained across the current distributional range of the
Mongolian oak during the LGM or earlier glacial periods. Though spatially
limited, postglacial expansions from these refugia have led to a pattern of
decreased genetic diversity with increasing latitude.
PMID- 26439084
TI - Drug-induced liver injury associated with Stevens-Johnson syndrome/toxic
epidermal necrolysis: Patient characteristics, causes, and outcome in 36 cases.
AB - The liver and skin are the organs most commonly involved in serious adverse drug
reactions. Rarely a drug reaction can affect both organs concurrently. The
association of drug-induced liver injury (DILI) and Stevens-Johnson syndrome
(SJS) or toxic epidermal necrosis (TEN) is even rarer and not well studied. We
describe our experience of DILI occurring in association with SJS/TEN including
the etiologic agents, clinical and biochemical characteristics, and outcome. We
identified patients who developed DILI in association with SJS/TEN from a
registry of DILI patients from a single center. Causality assessment for DILI and
SJS/TEN was carried out with the Roussel Uclaf Causality Assessment Method and
the Algorithm for Drug Causality for Epidermal Necrolysis, respectively. Among
748 consecutive patients with DILI from 1997 to March 2015, 36 (4.8%) had
associated features of SJS/TEN. The mean age was 32 years (females 19). Children
and patients with human immunodeficiency virus constituted 25% (n = 9) and 22% (n
= 8), respectively. Only a small number of "high-risk" drugs such as
antiepileptic agents, sulfonamides, and antiretroviral drugs accounted for the
majority of cases. Overall mortality was 36% (n = 13), which rose to 45.5% in the
presence of jaundice. Mortality was less in children 11% (n = 1) and human
immunodeficiency virus patients 12.5% (n = 1). CONCLUSIONS: DILI associated with
SJS/TEN is rare and associated with a high death rate, particularly in those with
jaundice; however, children and human immunodeficiency virus-infected individuals
have a favorable outcome; a small group of drugs contributed to a
disproportionate number of cases, and causality with Roussel Uclaf Causality
Assessment Method and the Algorithm for Drug Causality for Epidermal Necrolysis
was highly probable or probable in all cases.
PMID- 26439086
TI - True Blood: dengue virus evolution.
AB - This month's Genome Watch highlights insights into different selection pressures
in dengue virus evolution.
PMID- 26439087
TI - Possible Role of Phthalate in the Pathogenesis of Endometriosis: In Vitro,
Animal, and Human Data.
AB - CONTEXT: Although phthalates were shown to have several negative effects on
reproductive function in animals, its role in the pathogenesis of endometriosis
remains to be elucidated. OBJECTIVE: We aimed to investigate the in vitro and in
vivo effects of di-(2-ethylhexyl)-phthalate (DEHP) and to compare the urinary
levels of several phthalate metabolites between women with and without
endometriosis. DESIGN: For experimental studies, we used endometrial cell culture
and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse models.
We also performed a prospective case-control study for human sample analyses.
SETTING: The study was conducted at an academic center. MAIN OUTCOME MEASURES:
The activities of matrix metalloproteinase (MMP)-2 and 9, cellular invasiveness,
phosphorylation of extracellular signal-regulated kinase (Erk), and expression of
p21-activated kinase 4 were analyzed in endometrial cells treated with DEHP. The
implant size was compared between NOD/SCID mice fed with and without DEHP.
Urinary concentrations of several phthalate metabolites were compared between
women with and without endometriosis. RESULTS: In vitro treatment of endometrial
cells with DEHP led to significant increases of MMP-2 and 9 activities, cellular
invasiveness, Erk phosphorylation, and p21-activated kinase 4 expression. The
size of the endometrial implant was significantly larger in the NOD/SCID mice fed
with DEHP compared with those fed with vehicle. The urinary concentration of mono
(2-ethyl-5-hydroxyhexyl) phthalate, mono (2-ethyl-5-oxohexyl) phthalate, and mono
(2-ethyl-5-carboxyphentyl) phthalate were significantly higher in women with
endometriosis compared with controls. CONCLUSION: These findings strongly suggest
that exposure to phthalate may lead to establishment of endometriosis by
enhancing invasive and proliferative activities of endometrial cells.
PMID- 26439089
TI - Strong quantum confinement effect and reduced Frohlich exciton-phonon coupling in
ZnO quantum dots embedded inside a SiO2 matrix.
AB - ZnO quantum dots (QDs) embedded in an amorphous SiO2 matrix were examined in
depth by using variable-temperature photoluminescence (PL) and optical
reflectance spectroscopies. Compared with ZnO bulk crystals, ZnO quantum dots
with an average size of 4 nm exhibit a strong quantum confinement effect,
evidenced by a large blue shift in both PL and reflectance peaks of excitons.
More interestingly, a remarkably reduced long-range Frohlich interaction was
revealed in ZnO QDs. These fascinating effects may make ZnO QDs a very appealing
system in the fields of optoelectronics and others.
PMID- 26439088
TI - The Genetic Variant I148M in PNPLA3 Is Associated With Increased Hepatic Retinyl
Palmitate Storage in Humans.
AB - CONTEXT: Previous studies revealed that the common sequence variant I148M in
patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated
with liver fat content and liver diseases, but not with insulin resistance.
Recent data suggest that the PNPLA3 I148M variant has reduced retinyl-palmitate
lipase activity in hepatic stellate cells. OBJECTIVE: We hypothesized that the
PNPLA3 I148M variant is associated with elevated retinyl-palmitate storage in
human liver as a potential link to the clinical pathology. Design/Setting and
Participants: Using HPLC, we quantified the retinoid metabolites in liver tissue
extracts obtained from 42 human subjects, including 13 heterozygous and six
homozygous carriers of the minor PNPLA3 I148M variant. MAIN OUTCOME MEASURE:
Retinyl-palmitate is elevated in human livers of homozygous PNPLA3 I148M allele
carriers Results: The PNPLA3 I148M variant was associated with a significant
increase (1.4-fold) in liver fat. The content of retinyl-palmitate was elevated
and the ratio of retinol/retinyl-palmitate was reduced in liver extracts obtained
from homozygous PNPLA3 I148M minor allele carriers. In a multivariate model
including liver fat content, these differences remained significant independent
of liver fat content. The content of the minor retinyl-fatty acid esters was
similarly increased in homozygous PNPLA3 I148M carriers. CONCLUSIONS: The
increased content of hepatic retinyl-palmitate and the reduced ratio of
retinol/retinyl-palmitate in PNPLA3 I148M minor allele carriers support in vitro
findings of an altered retinyl-palmitate lipase activity. Our results indicate
that the PNPLA3 I148M variant is relevant for the retinyl-palmitate content in
human liver, providing a possible link to chronic liver disease.
PMID- 26439085
TI - Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg
virus.
AB - Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic
pathogens that cause severe disease in people, as highlighted by the latest Ebola
virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled
virus replication and the activation of host responses that contribute to
pathogenesis. Underlying these phenomena is the potent suppression of host innate
antiviral responses, particularly the type I interferon response, by viral
proteins, which allows high levels of viral replication. In this Review, we
describe the mechanisms used by filoviruses to block host innate immunity and
discuss the links between immune evasion and filovirus pathogenesis.
PMID- 26439090
TI - Late-onset arterial hemorrhage mimicking pseudoaneurysm after living donor liver
transplantation.
PMID- 26439091
TI - Helical Polybissilsesquioxane Bundles Prepared Using a Self-Templating Approach.
AB - Polybissilsesquioxanes with single-handed helical morphologies attracted much
attention during the last decade, which could be applied as asymmetric catalysts
and chiral stationary phases. Herein, a pair of chiral biphenylene-bridged
bissilsesquioxanes were synthesized. They self-assembled into helical bundles in
ethanol, behavior that was confirmed in field emission scanning electron
microscopy images. Circular dichroism analysis indicated that the biphenylene
groups twisted in a single-handed fashion. Single-handed helical
polybissilsesquioxane bundles were prepared via polycondensation of the
bissilsesquioxanes, using a self-templating approach. Because of the shrinkage
that occurred during polycondensation, the helical pitches of the bundles were
shorter than those of their corresponding organic self-assemblies. The wide-angle
X-ray diffraction pattern indicated that there were no pi-pi interactions among
the diphenylene groups. The circular dichroism spectra indicated that the
chirality was successfully transferred from the bissilsesquioxane self-assemblies
to the polybissilsesquioxane. The polybissilsesquioxanes displayed a capacity for
the adsorption of nitrobenzene and had potential application for
enantioseparation.
PMID- 26439092
TI - Myocyte-specific enhancer binding factor 2A expression is downregulated during
temporal lobe epilepsy.
AB - Myocyte-specific enhancer binding factor 2A (MEF2A) is a multifunctional nuclear
protein that regulates synaptogenesis, dendritic morphogenesis, and neuronal
survival. This study aimed to investigate the expression pattern of MEF2A in
epileptogenic processes. MEF2A expression was detected in 20 temporal neocortex
tissue samples from patients with temporal lobe epilepsy (TLE) and 20 samples
from trauma patients without epilepsy by real-time quantitative polymerase chain
reaction, immunohistochemistry, double-label immunofluorescent staining, and
western blot analysis. In addition, the expression patterns of MEF2A in the
hippocampus and adjacent cortex of a lithium-pilocarpine-induced TLE rat model
and control rats were examined. MEF2A was found to be expressed in the nuclei of
neurons but not in the dendrites of neurons and astrocytes. MEF2A expression was
significantly downregulated in temporal neocortex of humans and rats with TLE
compared to the control groups. In addition, in the lithium-pilocarpine-induced
TLE model, MEF2A expression dynamically decreased within 2 months. Taken
together, these data suggest that MEF2A is involved in the pathogenesis of TLE.
PMID- 26439093
TI - Superior mesenteric artery thrombosis after abrupt discontinuation of
rivaroxaban.
AB - We report a case of superior mesenteric artery thrombosis after the abrupt
discontinuation of rivaroxaban in a 59-year-old male patient. The initial
presentation was of sudden onset abdominal pain, nausea, vomiting, diarrhea, and
hematochezia in the setting of recently holding rivaroxaban anticoagulation for
an atrial flutter ablative procedure. Imaging revealed thrombosis of the superior
mesenteric artery and acute mesenteric ischemia requiring emergent surgical
intervention for embolectomy. Upon exploratory laparotomy, the bowel was found to
be viable, and an embolectomy with patch angioplasty was successful without
complication. This case illustrates the need for emergency medicine clinician
familiarity with this possible medication adverse event with rivaroxaban.
PMID- 26439094
TI - What do we miss without contrast in patients with flank pain?
AB - Flank pain is a common complaint in the emergency department, and the most
frequent cause of flank pain is urolithiasis. Spontaneous renal artery dissection
and renal artery thrombosis are rare causes of abdominal pain which can result in
renal parenchymal injury. They are mostly difficult to diagnose and treat in the
emergency setting. The present report describes 2 patients admitted to the
emergency department because of acute flank pain who were diagnosed with renal
infarction.
PMID- 26439095
TI - Impact of the emergency department streaming decision on patients' outcomes.
AB - BACKGROUND: Streaming occurs in emergency department (ED) to reduce crowding, but
misallocation of patients may impact patients' outcome. AIM: The study aims to
determine the outcomes of patients misallocated by the ED process of streaming
into likely admission or discharge. METHODS: This is a retrospective cohort
study, at an Australian, urban, tertiary referral hospital's ED between January
2010 and March 2012, using propensity score matching for comparison. Total and
partitioned ED lengths of stay, inpatient length of stay, in-hospital mortality
and 7- and 28-day unplanned readmission rate were compared between patients who
were streamed to be admitted against those streamed to be discharged. RESULTS:
Total ED length of stay did not differ significantly for admitted patients if
allocated to the wrong stream (median 7.6 h, interquartile range 5.7-10.6, cf.
7.5 h, 5.3-11.2; P = 0.34). The median inpatient length of stay was shorter for
those initially misallocated to the discharge stream (1.8 days, 1.1-3.0, cf. 2.4
days, 1.4-3.9; P < 0.001). In-hospital mortality and 7- and 28-day readmission
rates were not adversely affected by misallocation. When considering patients
eventually discharged from the ED, those allocated to the wrong stream stayed in
the ED longer than those appropriately allocated (5.2 h, 3.7-7.3, cf. 4.6 h, 3.3
6.4; P < 0.001). CONCLUSION: There were no significant adverse consequences for
an admitted patient initially misallocated by an ED admission/discharge streaming
process. Patients' discharge from the ED was slower if they had been allocated to
the admission stream. Streaming carries few risks for patients misallocated by
such a process.
PMID- 26439096
TI - Skin Lamellar Bodies are not Discrete Vesicles but Part of a Tubuloreticular
Network.
AB - Improved knowledge of the topology of lamellar bodies is a prerequisite for a
molecular-level understanding of skin barrier formation, which in turn may
provide clues as to the underlying causes of barrier-deficient skin disease. The
aim of this study was to examine the key question of continuity vs. discreteness
of the lamellar body system using 3 highly specialized and complementary 3
dimensional (3D) electron microscopy methodologies; tomography of vitreous
sections (TOVIS), freeze-substitution serial section electron tomography (FS
SET), and focused ion beam scanning electron microscopy (FIB-SEM) tomography. We
present here direct evidence that lamellar bodies are not discrete vesicles, but
are part of a tubuloreticular membrane network filling out the cytoplasm and
being continuous with the plasma membrane of stratum granulosum cells. This
implies that skin barrier formation could be regarded as a membrane
folding/unfolding process, but not as a lamellar body fusion process.
PMID- 26439097
TI - Hydrogen adsorption on nitrogen and boron doped graphene.
AB - Hydrogen adsorption on boron and nitrogen doped graphene is investigated in
detail by means of first-principles calculations. A comprehensive study is
performed of the structural, electronic, and magnetic properties of chemisorbed
hydrogen atoms and atom pairs near the dopant sites. The main effect of the
substitutional atoms is charge doping which is found to greatly affect the
adsorption process by increasing the binding energy at the sites closest to the
substitutional species. It is also found that doping does not induce magnetism
despite the odd number of electrons per atom introduced by the foreign species,
and that it quenches the paramagnetic response of chemisorbed H atoms on
graphene. Overall, the effects are similar for B and N doping, with only minor
differences in the adsorption energetics due to different sizes of the dopant
atoms and the accompanying lattice distortions.
PMID- 26439098
TI - Investigation of Humidity Dependent Surface Morphology and Proton Conduction in
Multi-Acid Side Chain Membranes by Conductive Probe Atomic Force Microscopy.
AB - In this report, we employ phase-contrast tapping mode and conductive probe atomic
force microscopy (cp-AFM) as tools to investigate the nanoscale morphology and
proton conductance of a 3M perfluoro-imide acid (PFIA) membrane (625 EW) over a
large range of relative humidity (3-95% RH). As a point of comparison, we also
investigate 3M perfluorosulfonic acid (PFSA) (825 EW) and Nafion 212. With AFM,
we assess the membrane's water retention and mechanical stability at low RH and
high RH, respectively. Cp-AFM allows us to spatially resolve the hydrophilic and
electrochemically active domains under a similar set of conditions and observe
directly the ties between membrane morphology and proton conductance. From our
data, we are able to correlate the improved water retention indicated by the size
of the hydrophilic domains with the proton conductance in the PFIA membrane at
elevated temperature and compare the result with that observed for the PFSA and
Nafion. At high RH conditions, we see evidence of a nearly continuous hydrophilic
phase, which indicates a high degree of swelling.
PMID- 26439100
TI - Microneedles for Transdermal Biosensing: Current Picture and Future Direction.
AB - A novel trend is rapidly emerging in the use of microneedles, which are a
miniaturized replica of hypodermic needles with length-scales of hundreds of
micrometers, aimed at the transdermal biosensing of analytes of clinical
interest, e.g., glucose, biomarkers, and others. Transdermal biosensing via
microneedles offers remarkable opportunities for moving biosensing technologies
and biochips from research laboratories to real-field applications, and envisages
easy-to-use point-of-care microdevices with pain-free, minimally invasive, and
minimal-training features that are very attractive for both developed and
emerging countries. In addition to this, microneedles for transdermal biosensing
offer a unique possibility for the development of biochips provided with end
effectors for their interaction with the biological system under investigation.
Direct and efficient collection of the biological sample to be analyzed will then
become feasible in situ at the same length-scale of the other biochip components
by minimally trained personnel and in a minimally invasive fashion. This would
eliminate the need for blood extraction using hypodermic needles and reduce, in
turn, related problems, such as patient infections, sample contaminations,
analysis artifacts, etc. The aim here is to provide a thorough and critical
analysis of state-of-the-art developments in this novel research trend, and to
bridge the gap between microneedles and biosensors.
PMID- 26439099
TI - Persistent behavioral effects following early life exposure to retinoic acid or
valproic acid in zebrafish.
AB - BACKGROUND: Moderate to severe dysregulation in retinoid signaling during early
development is associated with a constellation of physical malformations and/or
neural tube defects, including spina bifida. It is thought that more subtle
dysregulation of this system, which might be achievable via dietary (i.e.
hypervitaminosis A) or pharmacological (i.e. valproic acid) exposure in humans,
will manifest on behavioral domains including sociability, without overt physical
abnormalities. METHODS: During early life, zebrafish were exposed to low doses of
two chemicals that disrupt retinoid signaling. From 0 to 5dpf, larvae were reared
in aqueous solutions containing retinoic acid (0, 0.02, 0.2 or 2nM) or valproic
acid (0, 0.5, 5.0 or 50MUM). One cohort of zebrafish was assessed using a
locomotor activity screen at 6-dpf; another was reared to adulthood and assessed
using a neurobehavioral test battery (startle habituation, novel tank
exploration, shoaling, and predator escape/avoidance). RESULTS: There was no
significant increase in the incidence of physical malformation among exposed fish
compared to controls. Both retinoic acid and valproic acid exposures during
development disrupted larval activity with persisting behavioral alterations
later in life, primarily manifesting as decreased social affiliation.
CONCLUSIONS: Social behavior and some aspects of motor function were altered in
exposed fish; the importance of examining emotional or psychological consequences
of early life exposure to retinoid acting chemicals is discussed.
PMID- 26439101
TI - The foot of Homo naledi.
AB - Modern humans are characterized by a highly specialized foot that reflects our
obligate bipedalism. Our understanding of hominin foot evolution is, although,
hindered by a paucity of well-associated remains. Here we describe the foot of
Homo naledi from Dinaledi Chamber, South Africa, using 107 pedal elements,
including one nearly-complete adult foot. The H. naledi foot is predominantly
modern human-like in morphology and inferred function, with an adducted hallux,
an elongated tarsus, and derived ankle and calcaneocuboid joints. In combination,
these features indicate a foot well adapted for striding bipedalism. However, the
H. naledi foot differs from modern humans in having more curved proximal pedal
phalanges, and features suggestive of a reduced medial longitudinal arch. Within
the context of primitive features found elsewhere in the skeleton, these findings
suggest a unique locomotor repertoire for H. naledi, thus providing further
evidence of locomotor diversity within both the hominin clade and the genus Homo.
PMID- 26439102
TI - Three-Dimensional (3D) Bicontinuous Hierarchically Porous Mn2O3 Single Crystals
for High Performance Lithium-Ion Batteries.
AB - Bicontinuous hierarchically porous Mn2O3 single crystals (BHP-Mn2O3-SCs) with
uniform parallelepiped geometry and tunable sizes have been synthesized and used
as anode materials for lithium-ion batteries (LIBs). The monodispersed BHP-Mn2O3
SCs exhibit high specific surface area and three dimensional interconnected
bimodal mesoporosity throughout the entire crystal. Such hierarchical
interpenetrating porous framework can not only provide a large number of active
sites for Li ion insertion, but also good conductivity and short diffusion length
for Li ions, leading to a high lithium storage capacity and enhanced rate
capability. Furthermore, owing to their specific porosity, these BHP-Mn2O3-SCs as
anode materials can accommodate the volume expansion/contraction that occurs with
lithium insertion/extraction during discharge/charge processes, resulting in
their good cycling performance. Our synthesized BHP-Mn2O3-SCs with a size of ~700
nm display the best electrochemical performance, with a large reversible capacity
(845 mA h g(-1) at 100 mA g(-1) after 50 cycles), high coulombic efficiency
(>95%), excellent cycling stability and superior rate capability (410 mA h g(-1)
at 1 Ag(-1)). These values are among the highest reported for Mn2O3-based bulk
solids and nanostructures. Also, electrochemical impedance spectroscopy study
demonstrates that the BHP-Mn2O3-SCs are suitable for charge transfer at the
electrode/electrolyte interface.
PMID- 26439103
TI - Hand function assessment in the first years of life in unilateral cerebral palsy:
Correlation with neuroimaging and cortico-spinal reorganization.
AB - AIM: The purpose of the present study was to correlate early hand function
assessment during the first years of life with neuroimaging findings and the
different patterns of cortico-motor reorganization in children with unilateral
cerebral palsy (UCP). METHODS: We conducted a long prospective observational
study, in which 17 children with UCP (8 left-sided hemiplegia; Manual Ability
Classification System level 1-3) were first assessed at a mean age of 24 months
(range 18-28), and followed up by means of the Besta Scale, a new standardized
protocol assessing both unimanual and bimanual hand function. They also underwent
Melbourne Assessment of Unilateral Upper Limb Function (MUUL) and single-pulse
Transcranial Magnetic Stimulation (TMS) at a mean age of 10 years 5 months (range
9 y 1 m-12 y 8 m). Brain MRIs of all the 17 children were independently assessed
and scored by two blinded observers, according to a defined protocol. Possible
correlations between hand function at first assessment, neuroimaging and TMS data
were analyzed. RESULTS: Early hand function impairment significantly correlated
with the extension of brain damage (rho = -0.531, p = 0.028), number of involved
areas (rho = -0.608, p = 0.010), presence of radiological signs of cortico-spinal
degeneration (rho = -0.628, p = 0.007), and basal ganglia involvement (rho =
0.485, p = 0.049). Additionally, higher hand function scores (i.e. better hand
function) at first assessment significantly correlated with contralateral cortico
spinal projections, while lower scores significantly correlated with either mixed
or ipsilateral cortico-spinal projections to the affected hand (chi(2)(2) =
11.418, p = 0.003; post-hoc tests: contralateral TMS group versus ipsilateral: Z
= -2.943, p = 0.002 and contralateral TMS group versus mixed: Z = -2.775, p =
0.006). CONCLUSIONS: To our knowledge, this is the first study correlating hand
function assessment in the first years of life, and its evolution over time, with
neuroimaging and cortico-spinal projection patterns in children with UCP. These
findings could contribute to an improved prediction of prognosis and a better
delineation of therapeutic interventions in young children with UCP.
PMID- 26439104
TI - Analysis of T2 signal intensity helps in the differentiation between high and low
grade brain tumours in paediatric patients.
AB - PURPOSE: Previous studies hypothesized that the analysis of magnetic resonance
intensity of the solid portion in paediatric tumours can provide pre-surgical
information about the histopathology. Classically, high signal-intensity in
T2weighted (T2w) images identifies low-grade tumours, while anaplasia is
characterized by T2 hypointensity. We aimed to investigate if T2w signal
intensities can pre-operatively distinguish between low-grade and high-grade
brain tumours in paediatric patients. METHODS: Two raters, blinded to the
histological diagnosis, rated the signal intensity of MR images (T2w) from 36
children with newly diagnosed brain tumours, 17 children with low-grade brain
tumours and 19 children with high-grade brain tumours were included in this
study. Relative T2 values were obtained by dividing the T2w values of the solid
portion of the tumour by the T2w values of the vitreous humour. RESULTS: The best
cut-off point to distinguish low and high-grade paediatric brain tumours was 0.8.
If the signal intensity was less than or equal to 0.8 the tumour was expected to
be a high-grade tumour with a sensitivity of 100%. Prediction of a low-grade
tumour was more uncertain with a sensitivity of 70.5%. Overall, 86% of the
tumours would have been predicted correctly. CONCLUSION: Our data suggest that
T2w signal intensities of the solid portion of brain tumours in paediatrics can
pre-operatively differentiate between low-grade and high-grade tumours. In
addition, T2 hypointensity may be helpful in targeting stereotactic biopsy.
PMID- 26439105
TI - Continuous intra-arterial nimodipine infusion in patients with severe refractory
cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a feasibility study
and outcome results.
AB - BACKGROUND: Severe cerebral vasospasm is a major cause of death and disability in
patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet
available and hypertensive hypervolemic therapy (HHT) is often insufficient to
avoid delayed cerebral ischemia and neurological deficits. We compared patients
receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine
with a historical group treated with HHT and oral nimodipine alone. METHODS:
Between 0.5 and 1.2 mg/h of nimodipine were continuously administered by intra
arterial infusion via microcatheters either into the internal carotid or
vertebral artery or both, depending on the areas of vasospasm. The effect was
controlled via multimodal neuromonitoring and transcranial Doppler sonography.
Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6
months after the hemorrhage and compared to a historical control group. RESULTS:
Twenty-one patients received 28 intra-arterial nimodipine infusions. Six months
after discharge, the occurrence of cerebral infarctions was significantly lower
(42.6 %) in the nimodipine group than in the control group (75.0 %). This result
was reflected by a significantly higher proportion (76.0 %) of patients with good
outcome in the nimodipine-treated group, when compared to 10.0 % good outcome in
the control group. Median GOS was 4 in the nimodipine group and 2 in the control
group (p = 0.001). CONCLUSIONS: Continuous intra-arterial nimodipine infusion is
an effective treatment for patients with severe cerebral vasospasm who fail to
respond to HHT and oral nimodipine alone. Key to the effective administration of
continuous intra-arterial nimodipine is multimodal neuromonitoring and the
individual adaptation of dosage and time of infusion for each patient.
PMID- 26439106
TI - Photosensitized degradation kinetics of trace halogenated contaminants in natural
waters using membrane introduction mass spectrometry as an in situ reaction
monitor.
AB - The photochemically mediated dechlorination of polyhalogenated compounds
represents a potential decontamination strategy and a relevant environmental
process in chemically reducing media. We report the UV irradiation of natural and
artificial waters containing natural dissolved organic matter to effect the photo
sensitized degradation of chlorinated organic compounds, including
tetrachloromethane, 1,1,1-tricloroethane, perchloroethene, 1,2-dibromo-3
chloropropane and chlorobenzene at trace (ppb) levels in aqueous solution. The
degradation kinetics are followed in situ using membrane introduction mass
spectrometry. By re-circulating the reaction mixture in a closed loop
configuration over a semi-permeable hollow fiber polydimethylsiloxane membrane in
a flow cell interface, volatile and semi-volatile compounds are continuously
monitored using a quadrupole ion trap mass spectrometer. The time resolved
quantitative information provides useful mechanistic insights, including kinetic
data. Pseudo first-order rate constants for the degradation of contaminant
mixtures in natural waters are reported.
PMID- 26439107
TI - Asymptotically robust variance estimation for person-time incidence rates.
AB - Person-time incidence rates are frequently used in medical research. However,
standard estimation theory for this measure of event occurrence is based on the
assumption of independent and identically distributed (iid) exponential event
times, which implies that the hazard function remains constant over time. Under
this assumption and assuming independent censoring, observed person-time
incidence rate is the maximum-likelihood estimator of the constant hazard, and
asymptotic variance of the log rate can be estimated consistently by the inverse
of the number of events. However, in many practical applications, the assumption
of constant hazard is not very plausible. In the present paper, an average rate
parameter is defined as the ratio of expected event count to the expected total
time at risk. This rate parameter is equal to the hazard function under constant
hazard. For inference about the average rate parameter, an asymptotically robust
variance estimator of the log rate is proposed. Given some very general
conditions, the robust variance estimator is consistent under arbitrary iid event
times, and is also consistent or asymptotically conservative when event times are
independent but nonidentically distributed. In contrast, the standard maximum
likelihood estimator may become anticonservative under nonconstant hazard,
producing confidence intervals with less-than-nominal asymptotic coverage. These
results are derived analytically and illustrated with simulations. The two
estimators are also compared in five datasets from oncology studies.
PMID- 26439108
TI - A review of the changes to the licensing of influenza vaccines in Europe.
AB - In 2014, the European Committee for Medicinal Products for Human Use (CHMP)
published a draft regulatory guideline for the evaluation of influenza vaccines.
Following a public consultation round, the final guidance will be published in
the near future. Here, we highlight the main changes in the clinical section in
this guideline and discuss the background to these changes and whether the new
consolidated guidance document can be expected to achieve a better understanding
of the performance of seasonal, zoonotic and pandemic influenza vaccines during
the regulatory licensing process. The new influenza guideline reflects a changed
approach to the regulatory assessment of influenza vaccines, resulting in the
abolition of serological criteria, known as the CHMP criteria, which have been
the mainstay for evaluating the influenza vaccine immunogenicity for several
decades. The new guideline adopts a more diversified approach to the measurement
and reporting of the immune response to influenza vaccines and sets a requirement
to conduct clinical outcome trials in young children. Importantly, more emphasis
is placed on the post-licensure monitoring of the benefit risk of influenza
vaccines, including a request for continuous monitoring of efficacy and enhanced
safety surveillance. Despite the improvements these new requirements will
expectedly bring to the regulatory assessment of influenza vaccines, major
challenges remain which cannot be overcome by new guidance alone. Ongoing
initiatives in which academia, manufacturers, public health institutes and
regulators work together to address these challenges are central to the
development of robust tools to evaluate and monitor performance of influenza
vaccines in the future.
PMID- 26439109
TI - Preparation, characterisation and use for antioxidant oligosaccharides of a
cellulase from abalone (Haliotis discus hannai) viscera.
AB - BACKGROUND: In China, abalone (Haliotis discus hannai) production is growing
annually. During industrial processing, the viscera, which are abundant of
cellulase, are usually discarded or processed into low-value feedstuff. Thus, it
is of interest to obtain cellulase from abalone viscera and investigate its
application for preparation of functional oligosaccharides. RESULTS: A cellulase
was purified from the hepatopancreas of abalone by ammonium sulfate precipitation
and two-steps column chromatography. The molecular weight of the cellulase was 45
kDa on SDS-PAGE. Peptide mass fingerprinting analysis yielded 103 amino acid
residues, which were identical to cellulases from other species of abalone.
Substrate specificity analysis indicated that the cellulase is an endo-1,4-beta
glucanase. Hydrolysis of seaweed Porphyra haitanensis polysaccharides by the
enzyme produced oligosaccharides with degree of polymerisation of two to four,
whose monosaccharide composition was 58% galactose, 4% glucose and 38% xylose.
The oligosaccharides revealed 2,2'-diphenyl-1-picrylhydrazyl free radical as well
as hydrogen peroxide scavenging activity. CONCLUSION: It is feasible and
meaningful to utilise cellulase from the viscera of abalone for preparation of
functional oligosaccharides. (c) 2015 Society of Chemical Industry.
PMID- 26439110
TI - Language bias and self-rated health status among the Latino population: evidence
of the influence of translation in a wording experiment.
AB - PURPOSE: This research uses a translation experiment to assess the Spanish
translation of the "fair" response in the self-rated health measure among a
representative study of the Latino population in the USA. METHODS: Using a unique
Latino-specific survey (n = 1200), researchers built in a split sample approach
in the self-rated health status measure where half of the Spanish-speaking
respondents (n = 600) were randomly given "regular" and the other half were given
"Mas o Menos" in translating the English "fair" response. We first estimate a
logistic regression model to estimate differences across language categories on
the probability of reporting poor and fair health and then estimate a multinomial
logistic regression to test whether respondents who took the survey in Spanish
and given "regular" are more likely to rate their health as fair compared to
English speakers and Spanish-speaking respondents who are given the "Mas o Menos"
version. RESULTS: From our logistic regression model, we find that Spanish
speaking respondents given the "regular" response are more likely to report poor
health relative to English-speaking respondents and Spanish-speaking respondents
who were randomly given "Mas o Menos." The results from our multinomial logistic
models suggest that Spanish respondents provided with "Mas o Menos" are more
likely to rate their health as good relative to the base category of fair and
relative to both English and Spanish speakers given "regular." CONCLUSION: This
research informs the study of racial and ethnic disparities by providing a
detailed explanation for mixed findings in the Latino health disparities
literature. Researchers interested in self-rated health should translate the
general self-rated health option "fair" to "Mas o Menos" as our wording
experiment suggests that the current wording "regular" overinflates the reporting
of poor health.
PMID- 26439111
TI - Erratum to: An EQ-5D-5L value set based on Uruguayan population preferences.
PMID- 26439112
TI - Effects of Auditory Attention Training with the Dichotic Listening Task:
Behavioural and Neurophysiological Evidence.
AB - Facilitation of general cognitive capacities such as executive functions through
training has stirred considerable research interest during the last decade.
Recently we demonstrated that training of auditory attention with forced
attention dichotic listening not only facilitated that performance but also
generalized to an untrained attentional task. In the present study, 13
participants underwent a 4-week dichotic listening training programme with
instructions to report syllables presented to the left ear (FL training group).
Another group (n = 13) was trained using the non-forced instruction, asked to
report whichever syllable they heard the best (NF training group). The study
aimed to replicate our previous behavioural results, and to explore the
neurophysiological correlates of training through event-related brain potentials
(ERPs). We partially replicated our previous behavioural training effects, as the
FL training group tended to show more allocation of auditory spatial attention to
the left ear in a standard dichotic listening task. ERP measures showed
diminished N1 and enhanced P2 responses to dichotic stimuli after training in
both groups, interpreted as improvement in early perceptual processing of the
stimuli. Additionally, enhanced anterior N2 amplitudes were found after training,
with relatively larger changes in the FL training group in the forced-left
condition, suggesting improved top-down control on the trained task. These
results show that top-down cognitive training can modulate the left-right
allocation of auditory spatial attention, accompanied by a change in an evoked
brain potential related to cognitive control.
PMID- 26439113
TI - Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral
Hemorrhage: Potential Diagnostic Value?
AB - Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity
in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently
high uptake in healthy aged subjects. By detecting perfusion-like abnormalities,
early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1-6min) 11C-PiB
PET was obtained in 11 non-demented patients with probable CAA-related
symptomatic lobar intracerebral haemorrhage (70+/-7yrs), 9 age-matched healthy
controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase
atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the
CAA vs age-matched HC group. None of the age-matched controls fell below the
lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients
did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase
11C-PiB data did not change the sensitivity and specificity of late-phase PiB,
but combined early- and late-phase positivity entails a very high suspicion of
underlying Abeta-related clinical disorder, i.e., CAA or Alzheimer disease (AD).
In order to clarify this ambiguity, we then show that the occipital/posterior
cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data
suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with
respect to the unclear situation of late-phase positivity, but also help
differentiate CAA from AD.
PMID- 26439116
TI - Asymmetric bromine-lithium exchange: on the importance of both the diamine ligand
and the organolithium reagent.
AB - The asymmetric bromine-lithium exchange on a series of prochiral biphenyls was
investigated. As in many asymmetric organolithium reactions, the chiral ligand
(here a diamine) was considered to be the enantiocontrolling element. We show
here that the organolithium reagent also plays an important role.
PMID- 26439114
TI - Lifestyle advice with or without pelvic floor muscle training for pelvic organ
prolapse: a randomized controlled trial.
AB - INTRODUCTION AND HYPOTHESIS: We evaluated the effect of adding pelvic floor
muscle training (PFMT) to a structured lifestyle advice program. METHODS: This
was a single-blinded randomized trial of women with symptomatic pelvic organ
prolapse (POP) stage >= II. Participants were randomized to a structured
lifestyle advice program with or without PFMT. Both groups received similar
lifestyle advice in six separate group sessions. The combined group performed
group PFMT after an individual assessment. Primary outcome was a global
improvement scale at six-month follow-up. Secondary outcomes were the global
scale and objective POP at three-month follow-up, symptoms and quality of life
including sexuality, at three and six-month follow-up. A clinically relevant
change of symptoms was defined as >= 15 %. RESULTS: We included 109 women. Eighty
nine women (82 %) completed three months follow-up; 85 (78 %) completed six-month
follow-up. At both follow-ups, significantly more women in the combined group
reported improvement in the global scale. At the three-month follow-up, the
combined group only had significant improvement of POP symptoms while only the
lifestyle advice group had significant improvement of quality of life. Change in
objective POP and sexuality was nonsignificant. The symptom score improved 17 %
in the combined group and 14 % in the lifestyle advice group (P = 0.57).
Significantly more women in the lifestyle advice group had sought further
treatment at the six-month follow-up. CONCLUSION: Adding PFMT to a structured
lifestyle advice program gave superior results in a global scale and for POP
symptoms. Overall effect of either intervention barely reached clinical
relevance.
PMID- 26439115
TI - Detecting Horizontal Gene Transfer between Closely Related Taxa.
AB - Horizontal gene transfer (HGT), the transfer of genetic material between
organisms, is crucial for genetic innovation and the evolution of genome
architecture. Existing HGT detection algorithms rely on a strong phylogenetic
signal distinguishing the transferred sequence from ancestral (vertically
derived) genes in its recipient genome. Detecting HGT between closely related
species or strains is challenging, as the phylogenetic signal is usually weak and
the nucleotide composition is normally nearly identical. Nevertheless, there is a
great importance in detecting HGT between congeneric species or strains,
especially in clinical microbiology, where understanding the emergence of new
virulent and drug-resistant strains is crucial, and often time-sensitive. We
developed a novel, self-contained technique named Near HGT, based on the synteny
index, to measure the divergence of a gene from its native genomic environment
and used it to identify candidate HGT events between closely related strains. The
method confirms candidate transferred genes based on the constant relative
mutability (CRM). Using CRM, the algorithm assigns a confidence score based on
"unusual" sequence divergence. A gene exhibiting exceptional deviations according
to both synteny and mutability criteria, is considered a validated HGT product.
We first employed the technique to a set of three E. coli strains and detected
several highly probable horizontally acquired genes. We then compared the method
to existing HGT detection tools using a larger strain data set. When combined
with additional approaches our new algorithm provides richer picture and brings
us closer to the goal of detecting all newly acquired genes in a particular
strain.
PMID- 26439118
TI - Study of the activated macrophage transcriptome.
AB - Transcriptome analysis is a powerful modern tool to study possible alterations of
gene expression associated with human diseases. It turns out to be especially
promising for evaluation of gene expression changes in immunopathology, as immune
cells have flexible gene expression patterns that can be switched in response to
infection, inflammatory stimuli and exposure to various cytokines. In particular,
macrophage polarization towards pro-inflammatory (M1) and anti-inflammatory (M2)
phenotypes can be successfully studied using the modern transcriptome analysis
approaches. The two mostly used techniques for transcriptome analysis are
microarray and next generation sequencing. In this review we will provide an
overview of known gene expression changes associated with immunopathology and
discuss the advantage and limitations of different methods of transcriptome
analysis.
PMID- 26439117
TI - Dorsal Anterior Cingulate Thickness Is Related to Alexithymia in Childhood Trauma
Related PTSD.
AB - Alexithymia, or "no words for feelings", is highly prevalent in samples with
childhood maltreatment and posttraumatic stress disorder (PTSD). The dorsal
anterior cingulate cortex (dACC) has been identified as a key region involved in
alexithymia, early life trauma, and PTSD. Functional alterations in the dACC also
have been associated with alexithymia in PTSD. This study examined whether dACC
morphology is a neural correlate of alexithymia in child maltreatment-related
PTSD. Sixteen adults with PTSD and a history of childhood sexual abuse, physical
abuse, or exposure to domestic violence, and 24 healthy controls (HC) completed
the Toronto Alexithymia Scale 20 (TAS-20) and underwent magnetic resonance
imaging. Cortical thickness of the dACC was measured using FreeSurfer, and values
were correlated with TAS-20 scores, controlling for sex and age, in both groups.
Average TAS-20 score was significantly higher in the PTSD than the HC group. TAS
20 scores were significantly positively associated with dACC thickness only in
the PTSD group. This association was strongest in the left hemisphere and for TAS
20 subscales that assess difficulty identifying and describing feelings. We found
that increasing dACC gray matter thickness is a neural correlate of greater
alexithymia in the context of PTSD with childhood maltreatment. While findings
are correlational, they motivate further inquiry into the relationships between
childhood adversity, emotional awareness and expression, and dACC morphologic
development in trauma-related psychopathology.
PMID- 26439119
TI - Recurrence of endometriosis: risk factors, mechanisms and biomarkers.
AB - While the incidence of endometriosis is up to 40-60% in women with severe
dysmenorrhea/chronic pelvic pain, patients with subfertility carries a risk up to
20-30%. In symptomatic patients, although medical therapy is preferred in women
with endometriosis, surgery might be needed in nonresponders or patients with an
endometrioma. Following the surgery, recurrence of the disease and/or symptoms
might be still noticed which will progressively increase as times goes by.
Nevertheless, some risk factors have been identified for the risk of recurrence
that decreases the success of the procedure. Those risk factors might be
classified as patient-disease related and surgery-associated variables. Herein,
we will address about the management of endometriosis regarding the risk factors
for relapse, mechanisms of recurrence and potential biomarkers to predict the
event.
PMID- 26439120
TI - Perceptions of credibility of sexual abuse victims across generations.
AB - The success of prosecutions of perpetrators of sexual abuse often depends
substantially upon the perceived credibility of the victim witness. However,
perceptions of credibility may vary by generation of the observer, and the
constitution of juries may therefore lead to bias. In this study we examined
whether perceptions of credibility of female victims of sexual abuse varied
across generation Y, generation X, "baby boomers", and "builders". One hundred
and twenty-eight jury-eligible members of the community from each generation
(N=512) responded to ten questions assessing the perceived believability,
competence, trustworthiness, demeanour and sexual naivete of females providing
testimony related to alleged sexual abuse. Although consistent between-generation
differences were not found for all questions, or all four groups of generational
cohorts, in instances where significant differences were found, it was
consistently the older generation groups (builders and baby boomers) that
attributed less credibility to the victim than the younger generation groups
(generation Y and generation X). The implications of these findings are
discussed.
PMID- 26439121
TI - Cyanotoxin bioaccumulation in freshwater fish, Washington State, USA.
AB - Until recently, exposure pathways of concern for cyanotoxins have focused on
recreational exposure, drinking water, and dermal contact. Exposure to
cyanotoxins through fish consumption is a relatively new area of investigation.
To address this concern, microcystins and other cyanotoxins were analyzed in fish
collected from nine Washington lakes with recurrent toxic blooms using two types
of enzyme-linked immunosorbent assays (ELISAs) and liquid chromatography/mass
spectrometry/mass spectrometry (LC-MS/MS). Microcystins or microcystin-like
compounds were elevated in fish liver relative to muscle and other tissues
(liver>gut>muscle). Microcystin concentrations in fish fillet samples using anti
Adda ELISA (range 6.3-11 MUg/kg wet weight) were consistently higher in all fish
species than concentrations using anti-microcystin (MC)-leucine-arginine (LR)
ELISA (range 0.25-2.4 MUg/kg wet weight). MC-leucine-alanine (LA) was the only
variant detected in fish (2.5-12 MUg/kg in four livers) among the nine variants
analyzed by LC-MS/MS. Fish fillets showed no accumulation of the MCs targeted by
LC-MS/MS. Other cyanotoxins analyzed (anatoxin-a, saxitoxin, domoic acid, and
okadaic acid) were not detected in fish. Based on this and evidence from other
studies, we believe that people can safely consume two 8-oz fish fillet meals per
week from lakes with blooms producing MCs (clean the fish and discard viscera).
PMID- 26439122
TI - Occurrence and seasonal loads of pesticides in surface water and suspended
particulate matter from a wetland of worldwide interest--the Ria Formosa Lagoon,
Portugal.
AB - Two novel methods were developed to extract and quantify 56 pesticides in surface
waters, considering their content in both dissolved aqueous phase (DAP) and
suspended particulate matter (SPM) fractions. These procedures were applied to
coastal samples taken seasonally during 2012-2013, from three strategic sampling
sites along the Ria Formosa Lagoon (south of Portugal). Briefly, 500 mL of water
samples were filtrated, separating both fractions. The DAP fraction was extracted
and pre-concentrated by solid-phase extraction (SPE), while the SPM was extracted
using ultrasonic extraction technique (USE). Both fractions were then analyzed,
and the pesticides were quantified and identified, within 35 min, by gas
chromatography (GC) coupled to mass spectrometry (GC-MS and GC-MS/MS),
respectively. The extraction of pesticides from the SPM fraction showed average
recoveries of 102%, detection limits below 2.2 ng/L, and quantification limits
ranging from 0.3 to 6.6 ng/L. Considering the real water samples, 73% of the
selected pesticides were quantified in both DAP and SPM fractions (SigmaDAP+SPM
2.3 MUg/L) and their maximum levels were measured in autumn and winter. By
category, the global loads of fungicides, herbicides, and insecticides were ~407,
~323, and ~1.6 MUg/L, respectively. Thirty-one percent of the quantified
pesticides exceeded the European directives levels (2008/105/EC and 98/83/EC).
From the total loads, the SPM fraction contribution was 32%, showing the
importance of measuring pesticides in that fraction. The water physicochemical
parameters revealed that the total nitrogen amounts were very high relatively to
the legal required values, mainly close to the city of Faro (2.6 mg/L). In light
of the above, measures are in need to meet European directives and protect both
fauna and humans that use this area for leisure.
PMID- 26439123
TI - Comparative study of humic acid removal and floc characteristics by
electrocoagulation and chemical coagulation.
AB - The current study aims at investigating the efficiency of electrocoagulation for
the removal of humic acid from contaminated waters. In parallel, conventional
chemical coagulation was conducted to asses humic acid removal patterns. The
effect of varying contributing parameters (matrix pH, humic acid concentration,
type of electrode (aluminum vs. iron), current density, solution conductivity,
and distance between electrodes) was considered to optimize the
electrocoagulation process for the best attainable humic acid removal
efficiencies. Optimum removals were recorded at pH of 5.0-5.5, an electrical
conductivity of 3000 MUS/cm at 25 degrees C, and an electrode distance of 1 cm
for both electrode types. With aluminum electrodes, a current density of 0.05
mA/cm2 outperformed 0.1 mA/cm2 yet not higher densities, whereas a current
density of 0.8 mA/cm2 was needed for iron electrodes to exhibit comparable
performance. With both electrode types, higher initial humic acid concentrations
were removed at a slower rate but ultimately attained almost complete removals.
On the other hand, the best humic acid removals (~90%) by chemical coagulation
were achieved at 4 mg/L for both coagulants. Also, higher removals were attained
at elevated initial humic acid concentrations. Humic acid removals of 90% or
higher at an initial HA concentration of 40 mg/L were exhibited, yet alum
performed better at the highest experimented concentration. It was evident that
iron flocs were larger, denser, and more geometrical in shape compared to
aluminum flocs.
PMID- 26439124
TI - A review of the ecohydrology of the Sakumo wetland in Ghana.
AB - The Sakumo wetland is an internationally recognized Ramsar site located in a
largely urban area and provides essential ecological and social services to
wetland community dwellers. Despite its importance, the wetland has over the
years been subjected to human interference resulting in considerable risks of
deteriorating water quality, biodiversity loss, and drying up of most parts of
the wetland. The conversion of land for residential and agricultural uses has
significantly altered the hydrological characteristics of the land surface and
modified pathways and flow of water into the wetland. Other drivers identified
included drainage (mainly as runoff from agricultural farms), anthropogenic
pressure (waste discharge) due to infrastructure development associated with
urbanization, chemical contamination as a result of industrial and household
pollution, and unsustainable fishing practices (overfishing). The purpose of the
study was to review some of the physical and chemical properties of the Sakumo
wetland on the changing wetland resources with emphasis on water quality. Rapid
urbanization, industrialization, and overexploitation of wetland resources were
identified as key causative factors affecting the wetland functions. Their
effects on the wetland among others include increased nutrient and toxic chemical
load which has resulted in reduced wetland surface water quality and decrease in
species diversity. pH of the wetland waters was generally alkaline which is
characteristic of water bodies influenced by seawater under oxygenated
conditions. The increasing trends of electrical conductivity, phosphates,
ammonia, nitrate, and nitrite, though small, point to deteriorating water quality
in the wetland. The lagoon water was observed to be heavily polluted with
nutrients particularly phosphate. The sequence of nutrient in the wetland was
found to be in the order of PO4-P>NH3-N>NO3-N>NO2-N. These, if not checked, will
result in further deterioration of the wetland function. In order to protect the
wetland structure and function, it is recommended that a determination for both
surface water and groundwater (quality and quantity) components of the ecological
reserve (aquatic ecosystem) as well as the basic human need should be undertaken.
In addition, a complete hydrological study of the wetland must be done. This will
enable a well-balanced water allocation scheme to all users while still ensuring
long-term survival and sustainability of the wetland.
PMID- 26439125
TI - Holding-time and method comparisons for the analysis of fecal-indicator bacteria
in groundwater.
AB - As part of the US Geological Survey National Water-Quality Assessment Program,
groundwater samples from domestic- and public-supply wells were collected and
analyzed for fecal-indicator bacteria. A holding time comparison for total
coliforms, Escherichia coli, and enterococci was done by analyzing samples within
8 h using presence/absence methods and within 18-30 h using quantitative methods.
The data indicate that results obtained within 18-30 h were not significantly
different from those obtained within 8 h for total coliforms and enterococci, by
Colilert(r) and Enterolert(r) methods (IDEXX Laboratories Inc., Westbrook, ME),
respectively. Quantitative laboratory methods for samples analyzed within 18-30 h
showed a statistically significant higher detection frequency when compared to
presence/absence methods done within 8 h for the following methods, E. coli by
Colilert and enterococci by membrane filtration on mEI agar. Additionally, a
comparison of methods for the enumeration of enterococci was done. Using non
parametric statistical analyses, results from the two methods were statistically
different. In this study, the membrane filtration method on mEI agar was more
sensitive, resulted in more detections of enterococci, and results were easier to
interpret than with the quantitative Enterolert method. The quantitative
Enterolert method produced varying levels of fluorescence, which required
additional verification steps to eliminate false-positive results. It may be more
advantageous to analyze untreated groundwater for enterococci using the membrane
filtration method on mEI agar.
PMID- 26439126
TI - Microbiological quality of water from the rivers of Curitiba, Parana State,
Brazil, and the susceptibility to antimicrobial drugs and pathogenicity of
Escherichia coli.
AB - Water safety is determined by several markers, and Escherichia coli is one of the
most important indicators of water quality. The objective of this study was to
evaluate the microbiological parameters in environmental samples of fresh water
from rivers of Curitiba and its metropolitan area in Parana State, Brazil. In
addition, we evaluated the pathogenicity and susceptibility to antimicrobial
drugs in E. coli. These evaluations were performed by quantitative and
qualitative methods employing selective media for isolating thermotolerant
coliforms and biochemical tests for identifying E. coli. Pathogenic strains of E.
coli were detected by PCR multiplex using specific primers. From the water
samples, 494 thermotolerant coliforms were obtained, of which 96 (19.43%)
isolates were characterized as E. coli. Three isolates were identified as
enteroaggregative E. coli, one as enterotoxigenic E. coli, one as
enteropathogenic E. coli, and two carried the Eae virulence gene. E. coli
susceptibility to commonly employed antimicrobial drugs was analyzed by the disc
diffusion method. The results showed 49 (51.04%) isolates resistant to all the
drugs assayed, 16 (16.67%) with an intermediate resistance to all drugs, and 31
(32.29%) intermediately or fully resistant to one or more drugs tested. The
highest rate of resistance was observed for tetracycline 30 MUg, streptomycin 10
MUg, and ceftazidime 30 MUg. Detection of E. coli is associated with water
contamination by fecal material from humans and warm-blooded animals. The
occurrence of resistant strains can be the result of the indiscriminate use of
antimicrobial drugs and poor sanitation in the areas assayed.
PMID- 26439127
TI - Temperature-dependence of L-type Ca(2+) current in ventricular cardiomyocytes of
the Alaska blackfish (Dallia pectoralis).
AB - To lend insight into the overwintering strategy of the Alaska blackfish (Dallia
pectoralis), we acclimated fish to 15 or 5 degrees C and then utilized whole
cell patch clamp to characterize the effects of thermal acclimation and acute
temperature change on the density and kinetics of ventricular L-type Ca(2+)
current (I Ca). Peak I Ca density at 5 degrees C (-1.1 +/- 0.1 pA pF(-1)) was
1/8th that at 15 degrees C (-8.8 +/- 0.6 pA pF(-1)). However, alterations of the
Ca(2+)- and voltage-dependent inactivation properties of L-type Ca(2+) channels
partially compensated against the decrease. The time constant tau (tau) for the
kinetics of inactivation of I Ca was ~4.5 times greater at 5 degrees C than at
15 degrees C, and the voltage for half-maximal inactivation was shifted from
23.3 +/- 1.0 mV at 15 degrees C to -19.8 +/- 1.2 mV at 5 degrees C. These
modifications increase the open probability of the channel and culminate in an
approximate doubling of the L-type Ca(2+) window current, which contributes to
approximately 15% of the maximal Ca(2+) conductance at 5 degrees C.
Consequently, the charge density of I Ca (Q Ca) and the total Ca(2+) transferred
through the L-type Ca(2+) channels (Delta[Ca(2+)]) were not as severely reduced
at 5 degrees C as compared to peak I Ca density. In combination, the results
suggest that while the Alaska blackfish substantially down-regulates I Ca with
acclimation to low temperature, there is sufficient compensation in the kinetics
of the L-type Ca(2+) channel to support the level of cardiac performance required
for the fish to remain active throughout the winter.
PMID- 26439128
TI - Circadian Clock Genes Are Essential for Normal Adult Neurogenesis,
Differentiation, and Fate Determination.
AB - Adult neurogenesis creates new neurons and glia from stem cells in the human
brain throughout life. It is best understood in the dentate gyrus (DG) of the
hippocampus and the subventricular zone (SVZ). Circadian rhythms have been
identified in the hippocampus, but the role of any endogenous circadian
oscillator cells in hippocampal neurogenesis and their importance in learning or
memory remains unclear. Any study of stem cell regulation by intrinsic circadian
timing within the DG is complicated by modulation from circadian clocks elsewhere
in the brain. To examine circadian oscillators in greater isolation, neurosphere
cultures were prepared from the DG of two knockout mouse lines that lack a
functional circadian clock and from mPer1::luc mice to identify circadian
oscillations in gene expression. Circadian mPer1 gene activity rhythms were
recorded in neurospheres maintained in a culture medium that induces neurogenesis
but not in one that maintains the stem cell state. Although the differentiating
neural stem progenitor cells of spheres were rhythmic, evidence of any mature
neurons was extremely sparse. The circadian timing signal originated in
undifferentiated cells within the neurosphere. This conclusion was supported by
immunocytochemistry for mPER1 protein that was localized to the inner, more stem
cell-like neurosphere core. To test for effects of the circadian clock on
neurogenesis, media conditions were altered to induce neurospheres from BMAL1
knockout mice to differentiate. These cultures displayed unusually high
differentiation into glia rather than neurons according to GFAP and NeuN
expression, respectively, and very few BetaIII tubulin-positive, immature neurons
were observed. The knockout neurospheres also displayed areas visibly devoid of
cells and had overall higher cell death. Neurospheres from arrhythmic mice
lacking two other core clock genes, Cry1 and Cry2, showed significantly reduced
growth and increased astrocyte proliferation during differentiation, but they
generated normal percentages of neuronal cells. Neuronal fate commitment
therefore appears to be controlled through a non-clock function of BMAL1. This
study provides insight into how cell autonomous circadian clocks and clock genes
regulate adult neural stem cells with implications for treating neurodegenerative
disorders and impaired brain functions by manipulating neurogenesis.
PMID- 26439130
TI - Phytochemical Indicaxanthin Inhibits Colon Cancer Cell Growth and Affects the DNA
Methylation Status by Influencing Epigenetically Modifying Enzyme Expression and
Activity.
AB - BACKGROUND: Recently, we have shown anti-proliferative and pro-apoptotic effects
of indicaxanthin associated with epigenetic modulation of the onco-suppressor
p16INK4a in the human colon cancer cell line CACO2. In the present study, the
epigenetic activity of indicaxanthin and the mechanisms involved were further
investigated in other colorectal cancer cell lines. METHODS: LOVO1, CACO2, HT29,
HCT116, and DLD1 cells were used to evaluate the potential influence of
consistent dietary concentrations of indicaxanthin on DNA methylation, and the
epigenetic mechanisms involved were researched. RESULTS: Indicaxanthin exhibited
anti-proliferative activity in all cell lines but HT29, induced demethylation in
the promoters of some methylation-silenced onco-suppressor genes involved in
colorectal carcinogenesis (p16INK4a, GATA4, and ESR1), and left unchanged others
which were basally hypermethylated (SFRP1 and HPP1). In apparent contrast, cell
exposure to indicaxanthin increased DNMT gene expression, although indicaxanthin
appeared to be an inhibitor of DNMT activity. Indicaxanthin also increased the
expression of genes involved in DNA demethylation. Finally, an in silico
molecular modelling approach suggested stable binding of indicaxanthin at the
DNMT1 catalytic site. CONCLUSIONS: Our findings contribute to new knowledge in
the field of phytochemicals and specifically suggest dietary indicaxanthin as a
potential epigenetic agent to protect colon cells against tumoral alterations.
PMID- 26439129
TI - A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and
Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18-40 Year Old Subjects with
Diagnosed Atopic Dermatitis.
AB - BACKGROUND: Replicating smallpox vaccines can cause severe complications in
individuals with atopic dermatitis (AD). Prior studies evaluating Modified
Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a
favorable safety and immunogenicity profile in healthy volunteers. OBJECTIVE:
This Phase II study compared the safety and immunogenicity of MVA enrolling
groups of 350 subjects with AD (SCORAD <= 30) and 282 healthy subjects. METHODS:
Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks
apart. Adverse events, cardiac parameters, and the development of vaccinia virus
humoral immune responses were monitored. RESULTS: The overall safety of the
vaccine was similar in both groups. Adverse events affecting skin were
experienced significantly more often in subjects with AD, but the majority of
these events were mild to moderate in intensity. Seroconversion rates and
geometric mean titers for total and neutralizing vaccinia-specific antibodies in
the AD group were non-inferior compared to the healthy subjects. LIMITATIONS: The
size of the study population limited the detection of serious adverse events
occurring at a frequency less than 1%. CONCLUSION: MVA has a favorable safety
profile and the ability to elicit vaccinia-specific immune responses in subjects
with AD. TRIAL REGISTRATION: ClinicalTrials.gov NCT00316602.
PMID- 26439131
TI - Triple Antithrombotic Therapy after Percutaneous Coronary Intervention (PCI) in
Patients with Indication for Oral Anticoagulation: Data from a Single Center
Registry.
AB - Antithrombotic therapy consisting of a dual anti-platelet therapy (DAPT) and oral
anti-coagulation (OAC) with a vitamin k antagonist is often referred to as triple
therapy. This combined anticoagulation is applied in patients undergoing coronary
artery stent implantation while also having an indication for OAC. Triple therapy
increases the risk for bleeding events compared to either DAPT or OAC alone and
thereby might be associated with adverse outcomes. Clinical data on the frequency
of bleeding events in patients on triple therapy from clinical trials derives
from pre-selected patients and may differ from the real world patients. We report
data on patient characteristics and bleeding incidence of patients dismissed on
triple therapy from a single university hospital. Within the time span from
January 2000 to December 2012, we identified a total of 213 patients undergoing
PCI who were prescribed a triple therapy for at least 4 weeks (representing 0.86%
of all patients treated). The usage of triple therapy significantly increased
over the observed time period. The average CHA2DS2-VASc Score was 3.1 +/- 1.1
with an average HAS-BLED score of 2.5 +/- 0.86 representing a high-risk group for
thromboembolic events as well as considerable risk for bleeding events. An on
treatment bleeding incidence of 9.4% was detected, with gastrointestinal and
airway bleeding being the most frequent (5.1% and 1.4%, respectively). This is
consistent with data from clinical trials and confirms the high risk of bleeding
in patients on DAPT plus OAC. 29.0% of all patients receiving triple therapy had
an indication for OAC other than non-valvular atrial fibrillation. This
substantial patient group is underrepresented by clinical trials and needs
further attention.
PMID- 26439132
TI - BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and
primary peritoneal cancer.
AB - BACKGROUND: The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese
patients is still unclear. This study investigated the frequency of germline
mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian
tube cancer, regardless of their family histories, which were suggestive of
hereditary breast and ovarian cancer. METHODS: Ninety-five unselected women with
ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central
Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with
next-generation sequencing. RESULTS: Twelve of the 95 patients (12.6%), including
5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among
the 36 cases with a family history, 6 (16.7%) were found to carry mutations in
BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also
had BRCA1/2 germline mutations. There was no statistical difference between the 2
groups (P = .36). The presence of mutations and their clinical relevance were
studied. Mutation carriers were diagnosed at advanced stages (100% of positive
cases among stage III or IV cases) and had poor prognostic histological subtypes
(100% of positive cases had high-grade serous adenocarcinomas). CONCLUSIONS: In
this unselected Japanese population, approximately 13% of the cases with ovarian
cancer appeared to be associated with an inherited risk, regardless of a family
history. This finding indicates that BRCA1/2 genetic testing should be performed
for all patients with ovarian cancers.
PMID- 26439133
TI - Fecal Fistula Communicating with a Femur Shaft Fracture Secondary to a
Malpositioned Suprapubic Catheter: A Case Report.
AB - BACKGROUND: Suprapubic catheter (SPC) insertion is a common urological procedure.
Though considered a simple and safe procedure, complications are bound to occur
if proper precautions are not taken during the procedure. The reported
complications include gross hematuria, post-obstruction diuresis, insertion site
skin-related complications, and intra-abdominal visceral injuries. Iatrogenic
bowel injuries have been reported to occur as a complication in around 2.5% of
cases. CASE REPORT: We report a very rare case of a bowel injury due to improper
insertion of a SPC leading to fecal matter tracking along the muscle planes to
reach the fracture site of the femur shaft and formation of an external fecal
fistula along the lateral aspect of thigh, which according to us is the first
reported case in the literature. CONCLUSIONS: This case report shows the
devastating complication of a technically simple procedure done in an improper
manner and successful management of a rare case of femur fracture with
communicating fecal fistula. The purpose of this case report is to highlight the
importance of taking proper precautions before the procedure.
PMID- 26439134
TI - Molecular and Thermodynamic Factors Explain the Passivation Properties of
Poly(ethylene glycol)-Coated Substrate Surfaces against Fluorophore-Labeled DNA
Oligonucleotides.
AB - Poly(ethylene glycol) (PEG) nanofilms are used to avert the nonspecific binding
of biomolecules on substrate surfaces in biomedicine and bioanalysis including
modern fluorescence-based DNA sensing and sequencing chips. A fundamental and
coherent understanding of the interactions between fluorophore-tagged DNA, PEG
films, and substrates in terms of molecular and energetic factors is, however,
missing. Here we explore a large parameter space to elucidate how PEG layers
passivate metal oxide surfaces against Cy3-labeled DNA probes. The driving force
for probe adsorption is found to be the affinity of the fluorophore to the
substrate, while the high-quality PEG films prevent adsorption to bare ITO
surfaces. The amount of nonrepelled, surface-bound DNA strongly depends on
oligonucleotide size, PEG chain length, and incubation temperature. To explain
these observations, we develop an experimentally validated theory to provide a
microscopic picture of the PEG layer and show that adsorbed DNA molecules reside
within the film by end-tethering the fluorophore to the ITO surface. To
compensate for the local accumulation of negatively charged DNA, counterions
condense on the adsorbed probes within the layer. The model furthermore explains
that surface passivation is governed by the interdependence of molecular size,
conformation, charge, ion condensation, and environmental conditions. We finally
report for the first time on the detailed thermodynamic values that show how
adsorption results from a balance between large opposing energetic factors. The
insight of our study can be applied to rationally engineer PEG nanolayers for
improved functional performance in DNA analysis schemes and may be expanded to
other polymeric thin films.
PMID- 26439135
TI - High-Speed Intrinsic Dissolution Rate in One Minute Using the Single-Particle
Intrinsic Dissolution Rate Method.
AB - Intrinsic dissolution rate (IDR) has traditionally been determined from a
constant surface area of a substance. Here we present an optofluidic single
particle intrinsic dissolution rate (SIDR) method, by means of which real-time
determination of IDR from continuously changing effective surface areas of
dissolving individual microparticles, is possible. The changing surface area of
the individual microparticles is characterized through continuous random
orientation 3D particle morphology characterization during the dissolution
process. Using noninvasive optical monitoring and nonspecific image analysis, we
determined IDRs of a diverse set of substances from individual pure-substance
microparticles (14-747 MUg) with an average relative standard deviation of 9.4%.
A linear fit between SIDR and literature equilibrium solubility values (R(2) =
0.999) was achieved and kinetic solubility equivalent SIDRs were obtained, for
all substances, in as little as 1 min. Such miniaturized methods could become
valuable tools in drug discovery, by providing resource sparing higher quality
data acquisition means to replace current high-throughput solubility methods.
PMID- 26439137
TI - Looking for blood.
AB - In vivo imaging has revealed new details about how the malaria parasite enters
the bloodstream.
PMID- 26439136
TI - Outcome of VATS Lobectomy for Elderly Non-Small Cell Lung Cancer: A Propensity
Score-Matched Study.
AB - PURPOSE: To analyze the short-term and long-term outcome of video-assisted
thoracic surgery (VATS) lobectomy for elderly patients with non-small cell lung
cancer. METHODS: 105 patients aged >=75 years with resected non-small cell lung
cancer were matched with 105 younger patients by propensity score. Survival rates
were calculated by the Kaplan-Meier method. The cumulative incidence functions of
conditional survival rate according to the age of the patients were calculated by
competing risk analysis. RESULTS: patients >=75 years was associated with higher
postoperative complication rate (p <0.001), but similar perioperative death rate
(p = 0.006). Patients >=75 years were less likely to receive adjuvant
chemotherapy (p <0.001). The 5-year overall survival rates were 54.6% for
patients >=75 years and 74.1% for patients <75 years (p = 0.001). No difference
was seen in disease-free survival rate (59.5% vs. 71.9% respectively = 0.117).
The cumulative incidence functions of 5-year cancer-specific death were similar
between the two groups (28.7% vs. 24.6% respectively, p = 0.106). The cumulative
incidence functions of 5-year non-cancer-specific death was significantly higher
in the elderly group (18.7% vs. 1.0%, p <0.001). CONCLUSIONS: VATS lobectomy for
non-small-cell lung cancer in patients >=75 years were feasible with increased
morbidity but similar mortality. The resected elderly patients were more
frequently associated with non-cancer-specific death.
PMID- 26439138
TI - Maximal, Not Habitual, Walking Velocity is More Highly Correlated to Functional
Fitness of Community-Dwelling Older Adults.
AB - The aim of this investigation was to determine the relationship between usual and
maximal walking velocities with measures of functional fitness (FF). Fifty-seven
older adults (78.2 +/- 6.6 years) were recruited from a local retirement
community. All participants completed the following assessments: 10-m usual and
maximal walk, Short Physical Performance Battery (SPPB), 6-min walk (6MW), 8-foot
up-and-go (UPGO), and 30-s chair stand. Based on their SPPB performance, low (<=
9) and high (>= 10) FF groups were formed. Among all participants, maximal
walking velocity, not usual walking velocity, was significantly correlated with
SPPB (r = .35; p < .05 and r = .19; p > .05, respectively). In the high
functioning group, both maximal and usual walking velocities were correlated, but
correlation coefficients were stronger for all variables for maximal walking
velocity. These results suggest different walking conditions may be necessary to
use for high and low functioning older adults; specifically, maximal walking
velocity may be a preferred measure among high functioning older adults.
PMID- 26439139
TI - Abstracts of the 2015 CSEP General Meeting / Resumes de la 2015 Congres annuelle
de la SCPE.
PMID- 26439144
TI - Thickness and Microdomain Orientation of Asymmetric PS-b-PMMA Block Copolymer
Films Inside Periodic Gratings.
AB - The ordering process of asymmetric PS-b-PMMA block copolymers (BCPs) is
investigated on flat SiO2 surfaces and on topographically patterned substrates.
The topographic patterns consist of periodic gratings of 10 trenches defined by
conventional top-down approaches and subsequently neutralized using a P(S-r-MMA)
random copolymer (RCP). When the ordering process is accomplished on a flat
surface at a temperature ranging between 180 and 230 degrees C, cylindrical
microdomains perpendicularly oriented with respect to the substrate are observed
irrespective of annealing temperature. In contrast, when the ordering process
occurs on topographically patterned substrates, different phenomena have to be
considered. The simultaneous effect of the flow around the gratings and the BCP
flux from the zone located between adjacent trenches (mesa) into the inner part
of the trenches results in significant thickness variations of the confined BCP
film. Therefore, the amount of BCP inside the trenches depends on the width of
the mesa region, which acts as a BCP reservoir. Moreover, within each trench
group, the BCP thickness progressively decreases from the external to the central
trenches composing the periodic grating. The thickness variation of the BCP film
within the trenches strongly affects the ordering process, ultimately leading to
different orientations of the microdomains within the trenches. In particular,
when the annealing temperature is 190 degrees C a precise confinement of the BCP
within the trenches featuring a perpendicular cylinder morphology is observed. At
higher temperatures, mixed or parallel orientations of the microdomains are
obtained depending on the width of the trenches in the periodic grating.
PMID- 26439145
TI - Induced Production of Halogenated Epidithiodiketopiperazines by a Marine-Derived
Trichoderma cf. brevicompactum with Sodium Halides.
AB - Marine-derived Trichoderma sp. TPU199 (cf. T. brevicompactum) produced gliovirin
(1), pretrichodermamide A (2), and trichodermamide A (3) in a freshwater medium.
Compounds 1 and 2 are rare epidithiodiketopiperazines possessing an unusual
disulfide linkage. In the seawater medium, the strain biosynthesized the 5-chloro
5-deoxy derivatives (4 and 5) of 3 and 2. The production of 5 was proportional to
the concentration of seawater (NaCl). Therefore, 5-bromo-5-deoxy (6) and 5-deoxy
5-iodo (7) derivatives were biosynthesized in the freshwater media supplemented
with NaBr and NaI, respectively. The structure of a new iodo derivative (7) was
elucidated on the basis of its spectroscopic data.
PMID- 26439146
TI - Modeling C-reactive protein kinetic profiles for use as a clinical prediction
tool in patients with Staphylococcus aureus bacteremia.
AB - AIM: We hypothesized that C-reactive protein (CRP) kinetics can be accurately
modeled and might have clinical utility in a cohort of patients with
Staphylococcus aureus bacteremia. MATERIALS & METHODS: We constructed and
validated a nonlinear mixed effects model using CRP values obtained during the
first week of illness. RESULTS: Hematological malignancy, prosthetic heart valves
and metastatic seeding were identified as major covariates that influenced CRP
kinetics. When considering the presence of metastatic infection as an 'unknown',
the model could predict its presence through analysis of the observed CRP profile
with an Area-under-the-Receiver-Operator-Characteristic curve of 0.81, indicating
some diagnostic accuracy. CONCLUSION: We conclude that early CRP kinetics can be
accurately modeled and can help identify patients with metastatic seeding in S.
aureus bacteremia. Further validation is required.
PMID- 26439148
TI - Umbilical artery blood flows among pregnancies with single umbilical artery.
PMID- 26439147
TI - Colloidal Quantum Dot Photovoltaics Enhanced by Perovskite Shelling.
AB - Solution-processed quantum dots are a promising material for large-scale, low
cost solar cell applications. New device architectures and improved passivation
have been instrumental in increasing the performance of quantum dot photovoltaic
devices. Here we report photovoltaic devices based on inks of quantum dot on
which we grow thin perovskite shells in solid-state films. Passivation using the
perovskite was achieved using a facile solution ligand exchange followed by
postannealing. The resulting hybrid nanostructure created a more intrinsic CQD
film, which, when incorporated into a photovoltaic device with graded
bandstructure, achieved a record solar cell performance for single-step-deposited
CQD films, exhibiting an AM1.5 solar power conversion efficiency of 8.95%.
PMID- 26439149
TI - Stereotactic body radiotherapy of bone metastases in oligometastatic disease:
prognostic factors of oncologic outcomes.
AB - BACKGROUND: To evaluate the safety of stereotactic body radiotherapy (SBRT) of
bone metastases in oligometastatic disease and to investigate prognostic factors
of local control (LC), progression/disease-free survival (PDFS), and overall
survival (OS). METHODS: Eligibility criteria were number of metastates <=5,
controlled primary tumor without evidence of progression under systemic therapy,
exclusion of surgery, and no previous radiotherapy of the lesion of interest.
Oligometastatic status was classified into only bone (BOD) and outside bone
disease (OBOD), whereas SBRT was delivered to bone lesions using 2 different
schedules: 24 Gy/1 fraction or 27 Gy/3 fractions. A positron emission tomography
study of the lesion of interest was performed at baseline and at 3 months after
SBRT to evaluate metabolic response according to European Organization for
Research and Treatment of Cancer (EORTC) criteria. A Cox regression model was
used for univariate and multivariate analysis. RESULTS: Between January 2010 and
December 2013, 40 patients were enrolled. Only 1 patient experienced severe late
toxicity (radiation-related fracture). Local control was longer among responders'
than nonresponders' lesions (94.2% and 91.2% versus 63% and 35% at 1 and 2 years,
respectively) (p = 0.004; hazard ratio = 9.958). The multivariate analysis of
PDFS showed a significant correlation with planning target volume (PTV) size (p =
0.003) and oligometastatic status (p = 0.002). The multivariate analysis of OS
confirmed a statistically significant value of the oligometastatic status (p =
0.002) and a significant trend for PTV size (p = 0.065). CONCLUSIONS:
Stereotactic body radiotherapy is safe with a low incidence of severe toxicity.
Positron emission tomography response was a strong prognostic factor of LC
whereas BOD status and small PTV size could identify a subset of oligometastatic
patients at better prognosis.
PMID- 26439150
TI - Psychological screening of onco-hematologic inpatients: Distress Thermometer
administration.
AB - PURPOSE: The screening of psychological distress is a milestone in psycho
oncology. The National Comprehensive Cancer Network has established clinical
guidelines for detecting and managing it and the Distress Thermometer (DT) was
the recommended tool for the screening. Although its utility for oncologic
patients has been reported frequently in the literature, less is known about
hematologic patients. The present study involves a sample of onco-hematologic
adult patients. METHODS: In the current study, we proposed the Distress
Thermometer and the Problem List in a sample of hematologic inpatients at Ca'
Foncello Hospital, Treviso, Italy. We evaluated 102 patients, 61% male and 39%
female, median age 59 years (range 18-78). Enrolled patients had acute leukemia
(31%), multiple myeloma (31%), or lymphoma (31%). RESULTS: A total of 41.6% of
the patients presented psychological distress, and the DT score was associated
with neither sex nor diagnosis. The psychological distress was mild in 21.8%,
moderate in 13.8%, and severe in 12.9% of the patients. CONCLUSIONS: Our results
were consistent with previous results regarding the validation process of DT in a
large sample of Italian cancer patients.
PMID- 26439151
TI - Conventional Therapy in Adults With XLH Improves Dental Manifestations, But Not
Enthesopathy.
PMID- 26439154
TI - Letter to the Editor: Comments on Hormone Changes in Peripubertal Girls.
PMID- 26439155
TI - Letter to the Editor: Comment on "FGF21 Response to Critical Illness: Effect of
Blood Glucose Control and Relation With Cellular Stress and Survival" by Thiessen
S.E., et al.
PMID- 26439156
TI - Letter to the Editor: Possible Mechanisms of Hyponatremia-Induced Osteoporosis.
PMID- 26439157
TI - Response to the Letter to the Editor.
PMID- 26439158
TI - Letter to the Editor: "GLP-1 Receptor Agonist Treatment Increases Bone Formation
and Prevents Bone Loss in Weight-Reduced Obese Women" by Iepsen E.W., et al.
PMID- 26439159
TI - Response to the Letter by Napoli N., et al.
PMID- 26439160
TI - Letter to the Editor: Comment on Therapeutic Effectiveness of Screening for
Multiple Endocrine Neoplasia Type 2A by Machens A. and Dralle H.
PMID- 26439161
TI - Response to the Letter by Linane H.E. and Egan A.O.
PMID- 26439162
TI - Letter to the Editor: Parathyroidectomy Halts the Deterioration of Renal Function
in Primary Hyperparathyroidism.
PMID- 26439163
TI - Response to the Letter by Molitch M.E.
PMID- 26439164
TI - Microfluidic White Organic Light-Emitting Diode Based on Integrated Patterns of
Greenish-Blue and Yellow Solvent-Free Liquid Emitters.
AB - We demonstrated a novel microfluidic white organic light-emitting diode
(microfluidic WOLED) based on integrated sub-100-MUm-wide microchannels. Single
MUm-thick SU-8-based microchannels, which were sandwiched between indium tin
oxide (ITO) anode and cathode pairs, were fabricated by photolithography and
heterogeneous bonding technologies. 1-Pyrenebutyric acid 2-ethylhexyl ester (PLQ)
was used as a solvent-free greenish-blue liquid emitter, while 2,8-di-tert-butyl
5,11-bis(4-tert-butylphenyl)-6,12-diphenyltetracene (TBRb)-doped PLQ was applied
as a yellow liquid emitter. In order to form the liquid white light-emitting
layer, the greenish-blue and yellow liquid emitters were alternately injected
into the integrated microchannels. The fabricated electro-microfluidic device
successfully exhibited white electroluminescence (EL) emission via simultaneous
greenish-blue and yellow emissions under an applied voltage of 100 V. A white
emission with Commission Internationale de l'Declairage (CIE) color coordinates
of (0.40, 0.42) was also obtained; the emission corresponds to warm-white light.
The proposed device has potential applications in subpixels of liquid-based
microdisplays and for lighting.
PMID- 26439165
TI - DNA Structural Correlation in Short and Long Ranges.
AB - Recent single-molecule measurements have revealed the DNA allostery in
protein/DNA binding. MD simulations showed that this allosteric effect is
associated with the deformation properties of DNA. In this study, we used MD
simulations to further investigate the mechanism of DNA structural correlation,
its dependence on DNA sequence, and the chemical modification of the bases.
Besides a random sequence, poly d(AT) and poly d(GC) are also used as simpler
model systems, which show the different bending and twisting flexibilities. The
base-stacking interactions and the methyl group on the 5-carbon site of thymine
causes local structures and flexibility to be very different for the two model
systems, which further lead to obviously different tendencies of the
conformational deformations, including the long-range allosteric effects.
PMID- 26439166
TI - Ab initio molecular dynamics investigations of low-energy recoil events in Ni and
NiCo.
AB - Low-energy recoil events in pure Ni and the equiatomic NiCo alloy are studied
using ab initio molecular dynamics simulations. We found that the threshold
displacement energies are strongly dependent on orientation and weakly dependent
on composition. The minimum threshold displacement energies are along the [1 1 0]
direction in both pure Ni and the NiCo alloy. Compared to pure Ni, the threshold
displacement energies increase slightly in the NiCo alloy due to the stronger
bonds in the alloy, irrespective of the element type of the PKA. A single Ni
interstitial occupying the center of a tetrahedron formed by four Ni atoms and a
<1 0 0> split interstitial is produced in pure Ni by the recoils, while only the
<1 0 0> split interstitial is formed in the NiCo alloy. Compared to the
replacement sequences in pure Ni, anti-site defect sequences are observed in the
alloy, which have high efficiency for both producing defects and transporting
energy outside of the cascade core. These results provide insights into energy
transfer processes occurring in equiatomic alloys under irradiation.
PMID- 26439167
TI - Cryoglobulinaemia (IgG-kappa-type and IgM-gamma-type) with Occluding
Leukocytoclastic Vasculitis in a Patient with Vitiligo and Demyelinating
Polyneuropathy.
PMID- 26439169
TI - Direct Growth and Controlled Coalescence of Thick AlN Template on Micro-circle
Patterned Si Substrate.
AB - High-density micro-circle patterned Si substrates were successfully fabricated
for the direct overgrowth of thick AlN templates by using NH3 pulsed-flow
multilayer AlN growth and epitaxial lateral overgrowth techniques. The
experimental results show that an 8-MUm-thick AlN template was grown at a very
high growth rate on the substrates. The AlN template had full widths at half
maximum of 0.23 degrees and 0.37 degrees for the (002) and (102) reflection
planes in X-ray diffraction rocking curves. Atomic force microscopy and
transmission electron microscopy confirmed that the roughness of the surface was
low (3.5 nm) and the dislocation density was very low (1.5 * 10(8) cm(-2)
(screw), 3.7 * 10(8) (edge) cm(-2)).
PMID- 26439171
TI - Probing dispersion and re-agglomeration phenomena upon melt-mixing of polymer
functionalized graphite nanoplates.
AB - A one-step melt-mixing method is proposed to study dispersion and re
agglomeration phenomena of the as-received and functionalized graphite nanoplates
in polypropylene melts. Graphite nanoplates were chemically modified via 1,3
dipolar cycloaddition of an azomethine ylide and then grafted with polypropylene
graft-maleic anhydride. The effect of surface functionalization on the dispersion
kinetics, nanoparticle re-agglomeration and interface bonding with the polymer is
investigated. Nanocomposites with 2 or 10 wt% of as-received and functionalized
graphite nanoplates were prepared in a small-scale prototype mixer coupled to a
capillary rheometer. Samples were collected along the flow axis and characterized
by optical microscopy, scanning electron microscopy and electrical conductivity
measurements. The as-received graphite nanoplates tend to re-agglomerate upon
stress relaxation of the polymer melt. The covalent attachment of a polymer to
the nanoparticle surface enhances the stability of dispersion, delaying the re
agglomeration. Surface modification also improves interfacial interactions and
the resulting composites presented improved electrical conductivity.
PMID- 26439168
TI - Loss of KLF14 triggers centrosome amplification and tumorigenesis.
AB - Centrosome amplification is frequent in cancer, but the underlying mechanisms
remain unclear. Here we report that disruption of the Kruppel-like factor 14
(KLF14) gene in mice causes centrosome amplification, aneuploidy and spontaneous
tumorigenesis. Molecularly, KLF14 functions as a transcriptional repressor of
Plk4, a polo-like kinase whose overexpression induces centrosome overduplication.
Transient knockdown of KLF14 is sufficient to induce Plk4-directed centrosome
amplification. Clinically, KLF14 transcription is significantly downregulated,
whereas Plk4 transcription is upregulated in multiple types of cancers, and there
exists an inverse correlation between KLF14 and Plk4 protein expression in human
breast and colon cancers. Moreover, KLF14 depletion promotes AOM/DSS-induced
colon tumorigenesis. Our findings reveal that KLF14 reduction serves as a
mechanism leading to centrosome amplification and tumorigenesis. On the other
hand, forced expression of KLF14 leads to mitotic catastrophe. Collectively, our
findings identify KLF14 as a tumour suppressor and highlight its potential as
biomarker and therapeutic target for cancer.
PMID- 26439172
TI - Comparison of the Ramirez technique for the closure of large open
myelomeningocele defects with alternative methods.
AB - BACKGROUND: To compare the Ramirez technique for the operative closure of large
open myelomeningocele defects with conventional closure techniques in newborns.
We hypothesized that the immediate surgical treatment with the Ramirez technique
is superior to prior used operative techniques. METHODS: From 2003 to 2010, 23
children (8 female, 15 male) underwent closure of large open myelomeningocele
defects using the Ramirez technique (group A), while from 1993 to 2002, 23
children (6 female, 17 male) underwent conventional closure techniques (group B).
All children were included in the retrospective analysis with a mean follow-up
period of 3.4 years. RESULTS: Perioperative variables were similar in both groups
(P = ns). There were no hospital deaths in both groups. The operation time was
significantly higher in group A (228.7 +/- 76.8 versus 157.8 +/- 70.3 min, P =
0.003). Mean length of hospital stay was significantly lower in group A (30.7 +/-
16.4 days versus 52.0 +/- 38.5; P = 0.02). Postoperative complication rate was
significantly lower in group A (P = 0.01). Beyond postoperative day 10, liquor
fluid leakage was significantly lower in group A (P = 0.05). During follow-up,
there were no complications in group A. In group B, 2 children developed liquor
fistulas. CONCLUSIONS: The Ramirez technique allows efficient and safe closure of
large open myelomeningocele defects and reduces incidence of postoperative liquor
fistulae. The increased operation time and surgical efforts seem to be justified.
Treatment of large myelomeningocele defects requires an interdisciplinary team
including paediatrician-neonatologists, neurosurgeons and plastic surgeons.
PMID- 26439173
TI - Pectoralis major tear at its sternal origin after a seat-belt trauma.
PMID- 26439174
TI - Directed differentiation of definitive hemogenic endothelium and hematopoietic
progenitors from human pluripotent stem cells.
AB - The generation of hematopoietic stem cells (HSCs) from human pluripotent stem
cells (hPSCs) remains a major goal for regenerative medicine and disease
modeling. However, hPSC differentiation cultures produce mostly hematopoietic
progenitors belonging to the embryonic HSC-independent hematopoietic program,
which may not be relevant or accurate for modeling normal and disease-state adult
hematopoietic processes. Through a stage-specific directed differentiation
approach, it is now possible to generate exclusively definitive hematopoietic
progenitors from hPSCs showing characteristics of the more developmentally
advanced fetal hematopoiesis. Here, we summarize recent efforts at generating
hPSC-derived definitive hematopoiesis through embryoid body differentiation under
defined conditions. Embryoid bodies are generated through enzymatic dissociation
of hPSCs from matrigel-coated plasticware, followed by recombinant BMP4, driving
mesoderm specification. Definitive hematopoiesis is specified by a GSK3beta
inhibitor, followed by recombinant VEGF and supportive hematopoietic cytokines.
The CD34+ cells obtained using this method are then suitable for hematopoietic
assays for definitive hematopoietic potential.
PMID- 26439175
TI - Generating and characterizing the mechanical properties of cell-derived matrices
using atomic force microscopy.
AB - Mechanical interaction between cells and their surrounding extracellular matrix
(ECM) controls key processes such as proliferation, differentiation and motility.
For many years, two-dimensional (2D) models were used to better understand the
interactions between cells and their surrounding ECM. More recently, variation of
the mechanical properties of tissues has been reported to play a major role in
physiological and pathological scenarios such as cancer progression. The 3D
architecture of the ECM finely tunes cellular behavior to perform physiologically
relevant tasks. Technical limitations prevented scientists from obtaining
accurate assessment of the mechanical properties of physiologically realistic
matrices. There is therefore a need for combining the production of high-quality
cell-derived 3D matrices (CDMs) and the characterization of their topographical
and mechanical properties. Here, we describe methods that allow to accurately
measure the young modulus of matrices produced by various cellular types. In the
first part, we will describe and review several protocols for generating CDMs
matrices from endothelial, epithelial, fibroblastic, muscle and mesenchymal stem
cells. We will discuss tools allowing the characterization of the topographical
details as well as of the protein content of such CDMs. In a second part, we will
report the methodologies that can be used, based on atomic force microscopy, to
accurately evaluate the stiffness properties of the CDMs through the
quantification of their young modulus. Altogether, such methodologies allow
characterizing the stiffness and topography of matrices deposited by the cells,
which is key for the understanding of cellular behavior in physiological
conditions.
PMID- 26439177
TI - New developments in inhaler devices within pharmaceutical companies: A systematic
review of the impact on clinical outcomes and patient preferences.
AB - BACKGROUND: Pharmaceutical companies offer an increasing number of inhaler
devices, whether or not together with new substances, for maintenance treatment
of patients with COPD or asthma. However, well-designed studies to support these
developments are scarce. OBJECTIVES: The aim of this research was to evaluate how
far new developments of inhaler devices are scientifically supported and
translate into improvements of patient preferences and/or clinical outcomes.
METHODS: A systematic literature review was performed to retrieve randomised
controlled trials in patients with COPD or asthma that studied the in-company
evolution of inhaler devices. Results were tabulated and discussed. RESULTS: A
total of 30 studies were found comparing Respimat((r)) vs. HandiHaler((r)),
Diskus((r))(Accuhaler((r))) vs. Diskhaler((r))(Rotadisk((r))) or pMDI,
Ellipta((r)) vs. Diskus((r))(Accuhaler((r))), Nexthaler((r)) vs. pMDI, or
Breezhaler((r)) vs. Aerolizer((r)). These studies show that developments of
inhaler devices may improve patient satisfaction but do not lead to demonstrable
improvements in clinical efficacy. Current changes of devices are most commonly
parallelled by changes in administration frequency towards once daily treatment.
The only well-documented effect was found for the Respimat((r)) Soft MistTM
Inhaler, which realises a more than 3-fold lowering of the once-daily tiotropium
dose through increased performance of the inhaler device. There are however, no
data on clinical efficacy or safety comparing the two devices at the same dosage.
CONCLUSIONS: Future developments of inhaler devices should all require well
designed studies to demonstrate patient benefit.
PMID- 26439176
TI - Efficient cleavage of single and clustered AP site lesions within mono-nucleosome
templates by CHO-K1 nuclear extract contrasts with retardation of incision by
purified APE1.
AB - Clustered DNA damage is a unique characteristic of radiation-induced DNA damage
and the formation of these sites poses a serious challenge to the cell's repair
machinery. Within a cell DNA is compacted, with nucleosomes being the first order
of higher level structure. However, few data are reported on the efficiency of
clustered-lesion processing within nucleosomal DNA templates. Here, we show
retardation of cleavage of a single AP site by purified APE1 when contained in
nucleosomal DNA, compared to cleavage of an AP site in non-nucleosomal DNA. This
retardation seen in nucleosomal DNA was alleviated by incubation with CHO-K1
nuclear extract. When clustered DNA damage sites containing bistranded AP sites
were present in nucleosomal DNA, efficient cleavage of the AP sites was observed
after treatment with nuclear extract. The resultant DSB formation led to DNA
dissociating from the histone core and nucleosomal dispersion. Clustered damaged
sites containing bistranded AP site/8-oxoG residues showed no retardation of
cleavage of the AP site but retardation of 8-oxoG excision, compared to isolated
lesions, thus DSB formation was not seen. An increased understanding of
processing of clustered DNA damage in a nucleosomal environment may lead to new
strategies to enhance the cytotoxic effects of radiotherapeutics.
PMID- 26439179
TI - How Should We Follow-Up Asymptomatic Metal-on-Metal Hip Resurfacing Patients? A
Prospective Longitudinal Cohort Study.
AB - Current surveillance for metal-on-metal hip resurfacing (MoMHR) patients is not
evidence based. This study established changes that occurred in 152 asymptomatic
MoMHRs using repeat ultrasound and patient-reported outcomes. Factors associated
with (1) ultrasound progression and (2) developing new pseudotumors were
analyzed. Patients underwent repeat assessments 4.3 years later. Ultrasound
progression was observed in 19% (n = 29), with 10% (n = 15) developing new
pseudotumors. Key predictors of ultrasound progression included high blood cobalt
(P = .00013) and chromium (P = .00065), and high initial ultrasound grade (P =
.003) and volume (P = .036). No asymptomatic MoMHRs with initially normal metal
ions (<2 MUg/L) and normal ultrasounds (33% of cohort) developed new
pseudotumors. This patient subgroup does not require repeat follow-up within 5
years.
PMID- 26439178
TI - Combined effects of mild-to-moderate obesity and asthma on physiological and
sensory responses to exercise.
AB - Despite the close link between asthma and obesity, there are no studies that have
evaluated the sensory and physiological responses to exercise in obese
asthmatics. We recently demonstrated that normal weight asthmatics with well
controlled disease have preserved cardiorespiratory and sensory responses to
exercise relative to non-asthmatic controls. However, these similarities may not
hold true in patients with combined obesity and asthma. Accordingly, we sought to
determine if combined asthma and obesity was associated with deleterious effects
on cardiorespiratory fitness, exercise performance, dyspnoea, and physiological
responses to exercise. Fourteen well-controlled obese asthmatics and fourteen age
matched normal weight asthmatics performed routine spirometry and underwent an
incremental cardiopulmonary cycle test to assess the ventilatory, pulmonary gas
exchange, cardiovascular, and sensory responses to exercise. Groups were well
matched for age, height, spirometry, and asthma control. Obese asthmatics had a
significantly greater body mass index (33 +/- 3 vs. 23 +/- 1 kg/m(2), p < 0.001)
and lower self-reported activity levels by 47 % relative to normal weight
asthmatics (p < 0.05). Obese asthmatics had a significantly lower maximal oxygen
uptake (VO(2)) (82 +/- 14 vs. 92 +/- 10 %predicted) and work rate (75 +/- 8 vs.
89 +/- 13 %predicted) relative to normal weight asthmatics (p < 0.05). The
anaerobic threshold occurred at a lower VO(2) in obese asthmatics vs. normal
weight asthmatics (54 +/- 15 vs. 66 +/- 16 %predicted, p < 0.05). Ventilatory
responses were superimposed throughout exercise with no evidence of a ventilatory
limitation in either group. Cardiovascular responses were normal in both groups.
Dyspnoea responses were similar but the obese asthmatics experienced greater leg
fatigue ratings at submaximal work rates. In conclusion, obese individuals with
well controlled asthma have reduced cardiorespiratory fitness and greater leg
fatigue ratings relative to normal weight asthmatics. The relatively reduced
cardiorespiratory fitness and exercise performance in obese compared to normal
weight asthmatics is most likely driven by their more sedentary lifestyle and
resultant deconditioning rather than due to respiratory factors.
PMID- 26439180
TI - Comments on "Meta-analysis of randomised controlled trials of oral mandibular
advancement devices and continuous positive airway pressure for obstructive sleep
apnoea-hypopnoea" by Sharples et al.
PMID- 26439181
TI - Assessment of two multilocus sequence typing (MLST) schemes available for
Streptococcus mutans.
AB - OBJECTIVE: Two multilocus sequencing typing (MLST) schemes are currently
available for Streptococcus mutans. The first, introduced by Nakano et al. in
2007, consists of 8 conserved housekeeping genes. The second, introduced in 2010
by Do et al., includes 6 housekeeping genes and 2 putative virulence genes. The
purpose of the current study was to compare the two MLST schemes for use in
validating repetitive extragenic palindromic polymerase chain reaction (rep-PCR)
genotypes. DESIGN: Thirty-three S. mutans isolates, representing the 11 most
commonly occurring rep-PCR genotype groups, were selected for MLST. MLST was
performed with SYBR GreenTM PCR with published primers for both MLST schemes.
Amplicons were purified, sequenced, and data checked against the www.PubMLST.org
database for allelic and sequence type (ST) assignment. Discriminatory power,
congruence, and convenience criteria were evaluated. Concatenated sequences for
each scheme were analyzed using MEGA to generate phylogenetic trees using minimum
evolution with bootstrap. RESULTS: No significant difference in discriminatory
power was observed between the two MLST schemes for S. mutans. Clonal clusters
were consistent for both schemes. Overall, MLST demonstrated marginally greater
discriminatory power than rep-PCR; however all methods were found to be
congruent. New alleles and ST are reported for each scheme and added to the
PubMLST database. CONCLUSIONS: Clonality, supported by both methods and rep-PCR,
indicates S. mutans genotypes are shared between unrelated subjects. Both Nakano
and Do schemes demonstrates similar genotype discrimination for S. mutans
isolates suggesting each are well designed and may be used to verify rep-PCR
genotypes.
PMID- 26439182
TI - Utilization and Costs of Severe Uncontrolled Asthma in a Managed-Care Setting.
AB - BACKGROUND: Clinical and economic burden of patients with severe uncontrolled
asthma (SUA) in a real-world managed-care setting required further documentation.
OBJECTIVE: The objective of this study was to determine the characteristics,
clinical, and economic burden of SUA in a managed-care setting. METHODS: This
observational study identified patients with persistent asthma aged 12 years or
more (N = 25,935) using the International Classification of Diseases, 9th
Revision asthma codes and Healthcare Effectiveness Data and Information Set
administrative criteria. An SUA subgroup was identified when all of the following
3 criteria were met in 2012: (1) 2 or more asthma exacerbations; (2) 6 or more
medium- or high-dose dispensed canisters of inhaled corticosteroid (ICS) as
monotherapy or with long-acting beta2-agonist; and (3) 3 or more dispensed non
ICS controllers. Health care utilization and direct costs (all-cause and asthma
related) in 2013 were compared between SUA and non-SUA subgroups using
multivariable regression. RESULTS: Compared with the non-SUA subgroup (N =
25,350, 97.7%), the SUA subgroup (N = 585, 2.3%) at baseline was significantly
older and had more comorbidities, asthma specialist care, controller medication
dispensed, and asthma exacerbations. During follow-up, patients with SUA
exhibited significantly more asthma exacerbations and short-acting beta2-agonist
use, and higher all-cause and asthma-related costs than patients with non-SUA.
The adjusted asthma-related average direct cost per patient at follow-up was
significantly higher for SUA (mean +/- SE) ($2325 +/- $75) than non-SUA ($1261 +/
$9) with an incremental cost of $1056 (95% CI, $907-$1205). Asthma drugs
accounted for the major difference (incremental cost of $848/patient; 95% CI,
$737-$959). CONCLUSION: Increases and disparities in health care utilization and
direct cost by SUA status suggest that patients with SUA require more intensive
therapy, greater attention to adherence and comorbidities, more specialist care,
and, possibly, personalized treatment approaches including novel biologic
treatments.
PMID- 26439184
TI - Prospective multicentre study of the U-SENS test method for skin sensitization
testing.
AB - The U-SENSTM is a test method based on the human myeloid U937 cell line to assess
the skin sensitisation potential of substances. To demonstrate its robustness, a
multicentre validation study with four laboratories testing 24 coded substances
has been conducted according to internationally agreed principles. The primary
objective of the study was to enlarge the U-SENSTM's reproducibility database.
Secondary objectives were to provide additional evidence on its transferability
and its predictive capability. Reproducibility within laboratories was
approximately 92%, while the reproducibility between laboratories was 87.5%.
Predictivity for the 24 validation substances was high, with sensitivity,
specificity and accuracy being on average at least 93.8%. Similar performances
are obtained for 38 substances when combining the study results with those of an
earlier multicentre study, as well as with an automated version of the U-SENSTM.
With reliability and relevance similar to comparable non-animal skin
sensitisation test methods, which have achieved regulatory acceptance, it is
concluded that the U-SENSTM is a well reproducible and predictive test method.
This profiles the U-SENSTM as a valuable addition to the suite of non-animal
testing methods for skin sensitisation with the potential to significantly
contribute to the development of integrated testing strategies.
PMID- 26439183
TI - Gait parameters associated with balance in healthy 2- to 4-year-old children.
AB - The use of validated measurements of gait and balance are crucial to establish
baseline function and assess effectiveness of therapeutic interventions. Gait in
children changes with motor development requiring frequent observations to
effectively track progress. Standardized baseline spatiotemporal measurements and
a greater understanding of the relationship between gait and balance would
provide important feedback to clinicians regarding the effectiveness of
rehabilitation and guide treatment modifications. 84 subjects (2.0-4.9 years)
walked along the GAITRite((r)), a walkway that records spatiotemporal parameters.
The Pediatric Balance Scale (PBS) was administered to assess balance. Comparison
of spatiotemporal parameter means between age groups showed trends associated
with motor development similar to the ones described in the literature such as
decreased cadence and increased step/stride length with increasing age. However,
no significant differences in normalized spatiotemporal parameters were found
between age groups. Age, leg length, cadence, step/stride length, step/stance
time, and single/double support time showed significant correlation with balance
scores. When the parameters were grouped into spatial, temporal, and age-related
components using principal components analysis and included in a multiple
regression model, they significantly predicted 51% of the balance score variance.
Age-related components most strongly predicted balance outcomes. We suggest that
balance can potentially be evaluated by assessment of spatial, temporal, and age
related characteristics of gait such as step length, cadence, and leg length.
This suggests the possibility of developing new gait measurement technology that
could provide functional assessment and track improvements during rehabilitation
regimens. If the same model can be applied to monitor treatment efficacy in
children with gait abnormalities remains to be addressed.
PMID- 26439185
TI - Conditioned place preferences in humans using secondary reinforcers.
AB - The goal of this experiment was to examine whether a conditioned place preference
could be established in humans using a secondary reinforcer that provided little
obvious reward to the participants. Two experiments were conducted to answer this
question. In Experiment 1, 244 undergraduates were placed into a VR environment
consisting of two visually distinct rooms connected by a door. Throughout the
experiment, one room was randomly paired with occasional point rewards while the
other unique room was never paired with rewards. Participants received thee
pairings in each room. After a short break, a test session was administered, and
participants were given free access to the entire VR environment and no point
rewards were administered. On the test day, we observe that participants
displayed a significant CPP for the room paired with points, as evidenced by
significant differences in rating each of the rooms in terms of enjoyment. In
Experiment 2, 77 undergraduates were tested using a biased conditioning approach
in which an initial test session was conducted to obtain the participant's
preferred room bias, and then the least-preferred room was designated as the
points reward room for each participant. Using this biased conditioning approach,
participants spent a significantly greater amount of time in the points-paired
room. In this case, participants showed preferences based on explicit and
implicit measures. These results suggest new approaches to examine the role of
secondary reinforcers in nontraditional addictions such as internet, gaming, and
gambling dependencies.
PMID- 26439186
TI - Clinical Management of Vertebral Compression Fractures.
AB - Vertebral compression fractures (VCF's) are the most common form of osteoporotic
fractures. Whether symptomatic or asymptomatic, they both represent a high risk
for not only vertebral but also nonvertebral fractures in untreated populations.
This high risk of future fracture after a VCF is independent of the T-score
because bone strength is a combination of bone mineral density and bone quality.
VCFs are the single greatest risk for future fractures at all other skeletal
sites in untreated populations, including hip fractures. They are often
unrecognized despite their exceptionally high prevalence in all genders and most
ethnic groups as age increases. This article highlights some of the key messages
about VCF's, and how assessment for their presence and then management will
reduce the risk of all osteoporotic fractures.
PMID- 26439187
TI - Palladium Nanoribbon Array for Fast Hydrogen Gas Sensing with Ultrahigh
Sensitivity.
AB - A lithographically aligned palladium nano-ribbon (Pd-NRB) array with gaps of less
than 40 nm is fabricated on a poly(ethylene terephthalate) substrate using the
direct metal transfer method. The 200 MUm Pd-NRB hydrogen gas sensor exhibits an
unprecedented sensitivity of 10(9) % after bending treatment, along with fast
sensing behavior (80% response time of 3.6 s and 80% recovery time of 8.7 s) at
room temperature.
PMID- 26439188
TI - Brief Report: Immune Microenvironment Determines the Immunogenicity of Induced
Pluripotent Stem Cell Derivatives.
AB - The breakthrough of induced pluripotent stem cells (iPSCs) has raised the
possibility that patient-specific iPSCs can provide autologous cells for cell
therapy without the concern for immune rejection. However, the immunogenicity of
iPSC-derived cells remains controversial. Using syngeneic C57BL/6 (B6) mouse
transplantation model, several studies indicate that B6 iPSC-derived cells
exhibit some levels of immunogenicity when transplanted into B6 mice
subcutaneously. In contrast, one recent study has concluded that various lineages
of B6 iPSC-derived cells exhibit no immunogenicity when transplanted under the
kidney capsule of B6 mice. To resolve the controversy concerning this critical
issue of iPSC biology, we used the same B6 transplantation model to demonstrate
that the immune response toward antigens is dependent on the immune environment
of the transplantation site. Immunogenic antigen-expressing B6 embryonic stem
cells (ESCs) as well as B6 iPSCs and their terminally differentiated cells
survived under the kidney capsule but are immune rejected when transplanted
subcutaneously or intramuscularly. The cotransplantation of mature B6 dendritic
cells under the kidney capsule leads to immune rejection of B6 iPSC-derived
grafts but not B6 ESC-derived grafts, indicating that the lack of detectable
immune response to iPSC-derived grafts under the kidney capsule is due to the
lack of functional antigen presenting cells.
PMID- 26439189
TI - Citrus and melanoma risk: better to consume with dinner?
PMID- 26439190
TI - Novel strategy to decrease reperfusion injuries and improve function of cold
preserved livers using normothermic ex vivo liver perfusion machine.
AB - Normothermic extracorporeal liver perfusion (NELP) can decrease
ischemia/reperfusion injury to the greatest degree when cold ischemia time is
minimized. Warm perfusion of cold-stored livers results in hepatocellular damage,
sinusoidal endothelial cell (SEC) dysfunction, and Kupffer cell activation.
However, the logistics of organ procurement mandates a period of cold
preservation before NELP. The aim of this study was to determine the beneficial
effects of gradual rewarming of cold-stored livers by placement on NELP. Three
female porcine livers were used for each group. In the immediate NELP group,
procured livers were immediately placed on NELP for 8 hours. In the cold NELP
group, livers were cold-stored for 4 hours followed by NELP for 4 hours. In
rewarming groups, livers were cold-stored for 4 hours, then gradually rewarmed in
different durations to 38 degrees C and kept on NELP for an additional 4 hours.
For comparison purposes, the last 4 hours of NELP runs were considered to be the
evaluation phase. Immediate NELP livers had significantly lower concentrations of
liver transaminases, hyaluronic acid, and beta-galactosidase and had higher bile
production compared to the other groups. Rewarming livers had significantly lower
concentrations of hyaluronic acid and beta-galactosidase compared to the cold
NELP livers. In addition, there was a significant decline in international
normalized ratio values, improved bile production, reduced biliary epithelial
cell damage, and improved cholangiocyte function. Thus, if a NELP machine is not
available at the procurement site and livers will need to undergo a period of
cold preservation, a gradual rewarming protocol before NELP may greatly reduce
damages that are associated with reperfusion. In conclusion, gradual rewarming of
cold-preserved livers upon NELP can minimize the hepatocellular damage, Kupffer
cell activation, and SEC dysfunction.
PMID- 26439192
TI - Mapping the potential beverage quality of coffee produced in the Zona da Mata,
Minas Gerais, Brazil.
AB - BACKGROUND: Detailed knowledge of coffee production systems enables optimization
of crop management, harvesting and post-harvest techniques. In this study, coffee
quality is mapped as a function of coffee variety, altitude and terrain aspect
attributes. The work was performed in the Zona da Mata, Minas Gerais, Brazil.
RESULTS: A large range of coffee quality grades was observed for the Red Catuai
variety. For the Yellow Catuai variety, no quality grades lower than 70 were
observed. Regarding the terrain aspect, samples from the southeast-facing slope
(SEFS) and the northwest-facing slope (NWFS) exhibited distinct behaviors. The
SEFS samples had a greater range of quality grades than did the NWFS samples. The
highest grade was obtained from an NWFS point. The lowest quality values and the
largest range of grades were observed at lower altitudes. The extracts from the
highest-altitude samples did not produce any low-quality coffee. CONCLUSIONS: The
production site's position and altitude are the primary variables that influenced
the coffee quality. The study area has micro-regions with grades ranging from 80
to 94. These areas have the potential for producing specialty coffees. (c) 2015
Society of Chemical Industry.
PMID- 26439191
TI - Microbiota and host immune responses: a love-hate relationship.
AB - A complex relationship between the microbiota and the host emerges early at birth
and continues throughout life. The microbiota includes the prokaryotes, viruses
and eukaryotes living among us, all of which interact to different extents with
various organs and tissues in the body, including the immune system. Although the
microbiota is most dense in the lower intestine, its influence on host immunity
extends beyond the gastrointestinal tract. These interactions with the immune
system operate through the actions of various microbial structures and
metabolites, with outcomes ranging from beneficial to deleterious for the host.
These differential outcomes are dictated by host factors, environment, and the
type of microbes or products present in a specific ecosystem. It is also becoming
clear that the microbes are in turn affected and respond to the host immune
system. Disruption of this complex dialogue between host and microbiota can lead
to immune pathologies such as inflammatory bowel diseases, diabetes and obesity.
This review will discuss recent advances regarding the ways in which the host
immune system and microbiota interact and communicate with one another.
PMID- 26439193
TI - Improving discharge planning communication between hospitals and patients.
AB - BACKGROUND: A potential barrier to patient discharge from hospital is
communication problems between the treating team and the patient or family
regarding discharge planning. AIM: To determine if a bedside 'Leaving Hospital
Information Sheet' increases patient and family's knowledge of discharge date and
destination and the name of the key clinician primarily responsible for team
patient communication. METHODS: This article is a 'before-after' study of
patients, their families and the interdisciplinary ward-based clinical team.
Outcomes assessed pre-implementation and post-implementation of a bedside
'Leaving Hospital Information Sheet' containing discharge information for
patients and families. Patients and families were asked if they knew the key
clinician for team-patient communication and the proposed discharge date and
discharge destination. Responses were compared with those set by the team. Staff
were surveyed regarding their perceptions of patient awareness of discharge plans
and the benefit of the 'Leaving Hospital Information Sheet'. RESULTS: Significant
improvement occurred regarding patients' knowledge of their key clinician for
team-patient communication (31% vs 75%; P = 0.0001), correctly identifying who
they were (47% vs 79%; P = 0.02), and correctly reporting their anticipated
discharge date (54% vs 86%; P = 0.004). There was significant improvement in the
family's knowledge of the anticipated discharge date (78% vs 96%; P = 0.04).
Staff reported the 'Leaving Hospital Information Sheet' assisted with
communication regarding anticipated discharge date and destination (very helpful
n = 11, 39%; a little bit helpful n = 11, 39%). CONCLUSIONS: A bedside 'Leaving
Hospital Information Sheet' can potentially improve communication between
patients, families and their treating team.
PMID- 26439194
TI - Megakaryocytic differentiation of mouse embryonic stem cells via coculture with
immortalized OP9 stromal cells.
AB - Established from the calvaria of newborn macrophage colony-stimulating factor (M
CSF)-deficient mice, OP9 is a stromal cell line that used as a feeder layer to
support the in vitro differentiation of pluripotent stem cells into various
hematopoietic lineage cells, including granulocytes, erythrocytes, lymphocytes,
and megakaryocytes. However, as a primary culture cell line, OP9 can be used as
stromal cells for only 1 month. Therefore, to obtain functional OP9 cells,
numerous M-CSF-deficient newborn mice must be sacrificed. These limitations in
some ways restrict the application of OP9 cells in longterm and largescale
experiments. In this study, we used human papillomavirus 16 E6 and E7 genes to
generate immortalized OP9 stromal cells, designated I-OP9 cells, and then tested
their ability to support the megakaryocytic differentiation of pluripotent stem
cells in vitro. I-OP9 cells have similar morphology and properties as do parental
OP9 cells, and, as expected, have an extended lifespan and can support
megakaryocytic differentiation. Our data suggest that the method used in this
study, including establishing I-OP9 cells, enables the possibility to enlarge and
lengthen the scale of the experiment and, more critically, provides a humanistic
approach for preparing stromal cells that support the hematopoietic
differentiation of pluripotent stem cells in vitro.
PMID- 26439196
TI - A Meta-Analysis of Association Between Pesticides Exposure and Glioma Risk in
Adults.
PMID- 26439195
TI - Ectopic AP4 expression induces cellular senescence via activation of p53 in long
term confluent retinal pigment epithelial cells.
AB - When cells are grown to confluence, cell-cell contact inhibition occurs and
drives the cells to enter reversible quiescence rather than senescence. Confluent
retinal pigment epithelial (RPE) cells exhibiting contact inhibition was used as
a model in this study to examine the role of overexpression of transcription
factor AP4, a highly expressed transcription factor in many types of cancer, in
these cells during long-term culture. We generated stable inducible RPE cell
clones expressing AP4 or AP4 without the DNA binding domain (DN-AP4) and observed
that, when cultured for 24 days, RPE cells with a high level of AP4 exhibit a
large, flattened morphology and even cease proliferating; these changes were not
observed in DN-AP4-expressing cells or non-induced cells. In addition, AP4
expressing cells exhibited senescence-associated beta-galactosidase activity and
the senescence-associated secretory phenotype. We demonstrated that the induced
cellular senescence was mediated by enhanced p53 expression and that AP4
regulates the p53 gene by binding directly to two of the three E-boxes present on
the promoter of the p53 gene. Moreover, we showed that serum is essential for AP4
in inducing p53-associated cellular senescence. Collectively, we showed that
overexpression of AP4 mediates cellular senescence involving in activation of p53
in long-term post-confluent RPE cells.
PMID- 26439197
TI - Choroid Plexus Carcinoma in the External Ventricle of an Adult.
PMID- 26439198
TI - An Unusual Deadly Craniofacial Trauma Case Due To Hot Liquid Plastic Infusion.
PMID- 26439199
TI - Molluscum Contagiosum on the Lip.
PMID- 26439200
TI - Conventional Panoramic Radiograph Cannot Identify the Bifid Mandibular Canal.
PMID- 26439201
TI - Antibacterial Effects of Platelet-Rich Plasma in Promoting Facial Scars Healing
in Combination With Adipose-Derived Stromal Vascular Fraction Cells.
PMID- 26439202
TI - Pediatric Nevus Sebaceous of the Scalp: A Reconstructive Challenge.
PMID- 26439203
TI - Intradiploic Epidermoid Cyst in the Skull.
PMID- 26439204
TI - Fish Bone Induced Sialolith in Warthon Duct.
PMID- 26439205
TI - Surgical Treatment and Immediate Reconstruction of Keratocystic Odontogenic
Tumor.
PMID- 26439206
TI - Malignant Transformation of Facial Epidermoid Cyst With Distant Metastasis.
PMID- 26439207
TI - Age as a Risk Factor for Flap Failure in Free Tissue Transfer.
PMID- 26439208
TI - The Prolonged Double Vision Is not Only Caused by Adhesion of Orbital Contents
After Blowout Fractures: Important Role of the Orbital Proprioception.
PMID- 26439209
TI - Impure Blow-in Orbital Fracture With Severe Proptosis.
PMID- 26439210
TI - Hede: Postoperative Low-Flow Cerebrospinal Fluid Leak of Endoscopic Endonasal
Transsphenoidal Surgery for Pituitary Adenoma: Wait and See, or Lumbar Drain?
PMID- 26439211
TI - Clinical relevance of corrosion patterns attributed to inflammatory cell-induced
corrosion: A retrieval study.
AB - In vitro studies have shown that human osteoclasts can corrode stainless steel
and titanium leading to the production of metal ions responsible for inflammatory
reactions. Moreover, traces of cellular activities on metal orthopaedic explants
have recently been reported as inflammatory cell-induced (ICI) corrosion being
the result of the cells sealing on the metal surfaces and releasing reactive
oxygen species (ROS) through Fenton-like reactions. The extent and clinical
relevance of this phenomenon has yet to be understood. We analysed a cohort of
100 CoCr alloy hips collected at our retrieval centre; we performed macroscopic
and microscopic screening and used statistical analysis to correlate our findings
with implant and clinical variables. We found that 59% of our implants had
evidence of surface damage consistent with what has previously been described as
cell-induced corrosion. There was a significant association between the patterns
and aseptic loosening for the ASR modular (r = -0.488, p = 0.016) and the Durom
modular (r = 0.454, p = 0.026). This is the largest implant retrieval study to
examine the phenomena of so-called ICI corrosion and is the first to investigate
its clinical relevance. We recommend further work to determine the role of cells
in the damage patterns observed. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater
Res Part B: Appl Biomater, 105B: 155-164, 2017.
PMID- 26439212
TI - Osteomyelitis in adult patients on long-term parenteral nutrition: 2745 patient
years of experience in a national referral centre.
AB - BACKGROUND & AIMS: Osteomyelitis (OM) is a rare complication of catheter related
sepsis after central venous catheter (CVC) use. The prevalence, characteristics
and diagnosis of OM in patients with intestinal failure (IF) receiving long term
parenteral nutrition (PN) through CVCs have not previously been described.
METHODS: This was a retrospective study from a prospectively maintained database
of patients referred to a National IF centre. Age, IF aetiology, past medical
history, time on PN, OM site and organism(s) cultured were recorded. Patients
were divided into 2 groups: OM occurring in the setting of acute (Type 2) IF
(AIF) or chronic (Type 3) IF (CIF). Diagnosis of OM was made clinically and
supported by radiological and/or microbial evidence. RESULTS: 21 cases of OM
occurred in 17 patients (7 male (41%)) between 1994 and 2014. 0 cases were
observed between 1994 and 1999, 1 case between 2000 and 2004, 6 cases between
2005 and 2009 and 14 cases between 2010 and 2014. There were 11 cases in 7
patients with CIF managed at the IFU between 1994 and 2014; the latter yielded a
period prevalence for OM of 0.9% when compared to the 794 HPN patients managed by
the IFU over this period. There were 10 cases of OM in 10 patients with AIF;
patients with AIF had spent less time on PN before developing OM, compared to
patients with CIF; despite this, the rate of preceding CVC infections was higher
in the AIF (5.6/1000 catheter days) than in the CIF (0.3/1000 catheter days)
group, as a result of patients with AIF contracting CVC infections prior to
specialist referral. Patients with AIF had more severe OM compared to those with
CIF, according to the Cierny Mader classification. All patients received at least
6 weeks antimicrobial chemotherapy. 4/10 (40%) AIF cases and 2/11 (18%) CIF cases
required surgical intervention. No patient died from OM or its treatment.
CONCLUSION: OM is a rare complication of IF and its treatment, but is being
diagnosed more frequently than before and should be noted as a potential focus of
sepsis in patients with IF, because it may lead to considerable morbidity.
PMID- 26439213
TI - Combining mechanistic and data-driven approaches to gain process knowledge on the
control of the metabolic shift to lactate uptake in a fed-batch CHO process.
AB - A growing body of knowledge is available on the cellular regulation of overflow
metabolism in mammalian hosts of recombinant protein production. However, to
develop strategies to control the regulation of overflow metabolism in cell
culture processes, the effect of process parameters on metabolism has to be well
understood. In this study, we investigated the effect of pH and temperature shift
timing on lactate metabolism in a fed-batch Chinese hamster ovary (CHO) process
by using a Design of Experiments (DoE) approach. The metabolic switch to lactate
consumption was controlled in a broad range by the proper timing of pH and
temperature shifts. To extract process knowledge from the large experimental
dataset, we proposed a novel methodological concept and demonstrated its
usefulness with the analysis of lactate metabolism. Time-resolved metabolic flux
analysis and PLS-R VIP were combined to assess the correlation of lactate
metabolism and the activity of the major intracellular pathways. Whereas the
switch to lactate uptake was mainly triggered by the decrease in the glycolytic
flux, lactate uptake was correlated to TCA activity in the last days of the
cultivation. These metabolic interactions were visualized on simple mechanistic
plots to facilitate the interpretation of the results. Taken together, the
combination of knowledge-based mechanistic modeling and data-driven multivariate
analysis delivered valuable insights into the metabolic control of lactate
production and has proven to be a powerful tool for the analysis of large
metabolic datasets.
PMID- 26439214
TI - Home Invasion Homicide Offenders: An Analysis of Subsequent Prison Rule
Violations.
AB - This study adds to the small body of research on home invasion by describing the
circumstances surrounding home invasions that resulted in the death of a
resident. The 2 most common types of home invasion homicides (HIHs) involved
"drug ripoffs" and robberies of older adults for money and property. The study
also examined subsequent rule-violating behavior of 132 HIH inmates while
incarcerated. The rate of rule violations among HIH inmates was similar to a
broader cohort of incarcerated homicide offenders. A logistic regression model
identified variation in assaultive prison behavior based on some routine
predictors (age, education, race, and prior imprisonment) and 2 associated with
the crime (method of killing and age by gender of victims).
PMID- 26439215
TI - The S-stamp in Descemet Membrane Endothelial Keratoplasty Safely Eliminates
Upside-down Graft Implantation.
AB - PURPOSE: To present 6-month clinical outcomes from a series of 165 consecutive
Descemet membrane endothelial keratoplasty (DMEK) procedures before and after the
introduction of a novel stromal-sided S-stamp preparation technique that has
decreased the incidence of iatrogenic primary graft failure by eliminating upside
down grafts. DESIGN: Retrospective nonrandomized comparative case series.
PARTICIPANTS: We included 165 consecutive eyes that had undergone DMEK surgery
for Fuchs' or pseudophakic bullous keratopathy. These cases were divided into 2
cohorts: the first cohort comprised 31 cases that used unstamped tissue before
the S-stamp was introduced, and the second cohort comprised 133 cases after the S
stamp was incorporated into the standardized technique. A single unstamped DMEK
case was performed after the introduction of the S-stamp for a total of 32
unstamped cases. METHODS: Donor materials were prepared at a single eye bank
using a standardized technique, which subsequently incorporated the addition of a
dry ink gentian violet S-stamp to the stromal side of Descemet membrane. All
surgeries were performed at a single clinical site by 5 surgeons (2 attending
surgeons and 3 fellows). Two of the 165 DMEK cases were performed for
pseudophakic bullous keratopathy (2 cases, 1 in each cohort), and the remaining
cases were for Fuchs' endothelial dystrophy. Primary outcome measures were
assessed at 6 months and maintained in a prospective institutional review board
approved study. MAIN OUTCOME MEASURES: We analyzed the 6-month endothelial cell
density, incidence of iatrogenic primary graft failure, upside-down graft
implantation, and rebubble events. RESULTS: The S-stamp eliminated upside-down
graft implantations (0/133 S-stamped vs 3/32 unstamped) and did not significantly
alter 6-month endothelial cell loss (31+/-17% S-stamped vs 29+/-14% unstamped; P
= 0.62) or frequency of rebubble (17/133 S-stamped vs 1/32 unstamped; P = 0.20).
CONCLUSION: The incorporation of a stromal-sided S-stamp eliminates iatrogenic
primary graft failure owing to upside-down implantation of DMEK grafts, without
adversely affecting early postoperative complications or 6-month endothelial cell
loss.
PMID- 26439216
TI - Julian Robert Frayne (1935-2015).
PMID- 26439217
TI - Missed diagnosis of brilliance in a colleague.
PMID- 26439218
TI - Using PET and CT imaging to define the radiotherapy target for tumours that move
with respiration.
PMID- 26439220
TI - Instantaneous Click Chemistry by a Copper-Containing Polymeric-Membrane-Installed
Microflow Catalytic Reactor.
AB - The copper(I)-catalyzed Huisgen cycloaddition (azide-alkyne cycloaddition) is an
important reaction in click chemistry that ideally proceeds instantaneously. An
instantaneous Huisgen cycloaddition has been developed that uses a novel
catalytic dinuclear copper complex-containing polymeric membrane-installed
microflow device. A polymeric membranous copper catalyst was prepared from poly(4
vinylpyridine), copper(II) sulfate, sodium chloride, and sodium ascorbate at the
interface of two laminar flows inside microchannels. Elucidation of the structure
by XANES, EXAFS, and elemental analysis, as well as second-order Moller-Plesset
perturbation theory (MP2) calculations and density functional theory (DFT)
calculations assigned the local structure near Cu as a MU-chloro dinuclear Cu(I)
complex. The microflow device promotes the instantaneous click reaction of a
variety of alkynes and organic azides to afford the corresponding triazoles in
quantitative yield.
PMID- 26439221
TI - Reply.
PMID- 26439222
TI - The more you look, the more you will find.
PMID- 26439223
TI - Possible influence of AMPD1 on cholinergic neurotransmission and sleep.
AB - It is known that adenosine excess due to monophosphate deaminase deficiency
(AMPD1) can be linked to muscle problems. Recently, Perumal et al., 2014 reported
a first case of possible impact of AMPD1 on sleep, REM sleep and cholinergic
neurotransmission. We report a second patient with similar sleep complaints: long
sleep duration with residual daytime sleepiness and a need to sleep after
exercise. On polysomnography we observed a long sleep duration, with high sleep
efficiency and a SOREMP; on MSLT a shortened sleep latency and 4 SOREMPS were
observed. Frequency power spectral heart rate analysis during slow wave sleep,
REM sleep and wakefulness revealed an increased parasympathetic tone. In
conclusion, AMPD1 could have a profound influence on cholinergic
neurotransmission and sleep; further studies are mandatory.
PMID- 26439224
TI - Expression of TP53, BCL-2, and VEGFA Genes in Esophagus Carcinoma and its
Biological Significance.
AB - BACKGROUND: The pathogenesis of esophagus carcinoma involves a cascade process
consisting of multiple factors and accumulation of gene mutations. It is known
that vascular endothelial growth factor (VEGF) mainly regulates de novo vascular
formation while B-cell lymphoma-2 (BCL-2) gene exerts a tumor-suppressing effect.
The prominent expression of VEGFA and BCL-2 genes, along with the most famous
tumor-suppressor gene, TP53, raise the possibly of gene interaction. This study
therefore investigated the effect and correlation of TP53, BCL-2, and VEGFA genes
on cell proliferation and apoptosis of esophagus carcinoma. MATERIAL AND METHODS:
A total of 30 male rats were prepared by subcutaneous injection of methyl-benzyl
nitrosamine (MBNA) to induce esophagus cancer, along with 30 controlled rats
which received saline instead. After 4, 10, 20, or 30 weeks, rats were sacrificed
to observe the morphological changes of esophageal mucosa. Cell apoptosis was
quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick-end
labeling (TUNEL) assay. Immunohistochemical (IHC) staining was employed to
examine the expression of TP53, BCL-2 and VEGFA genes. RESULTS: With the
progression of cancer, pathological damages of esophageal tissue aggravated while
the cancer cell apoptosis gradually decreased compared to controlled animals.
Protein levels of p53, Bcl-2, and VEGF in the model group were significantly
elevated at each time point. Positive correlations existed between p53 and Bcl-2
or VEGF. CONCLUSIONS: Abnormally elevated expression of TP53, BCL-2, and VEGFA
genes may participate in the proliferation of esophagus cancer cells in a
synergistic manner.
PMID- 26439225
TI - Fast Liquid Transfer between Surfaces: Breakup of Stretched Liquid Bridges.
AB - In this work, a systematic experimental study was performed to understand the
fast liquid transfer process between two surfaces. According to the value of the
Reynolds number (Re), the fast transfer is divided into two different scenarios,
one with negligible inertia effects (Re ? 1) and the other with significant
inertia effects (Re > 1). For Re ? 1, the influences of the capillary number (Ca)
and the dimensionless minimum separation (H(min)* = H(min)/V(1/3), where H(min)
is the minimum separation between two surfaces and V is the volume of liquid) on
the transfer ratio (alpha, the volume of liquid transferred to the acceptor
surface over the total liquid volume) are discussed. On the basis of the roles of
each physical parameter, an empirical equation is presented to predict the
transfer ratio, alpha = f(Ca). This equation involves two coefficients which are
affected only by the surface contact angles and H(min)* but not by the liquid
viscosity or surface tension. When Re > 1, it is shown for the first time that
the transfer ratio does not converge to 0.5 with the increase in the stretching
speed.
PMID- 26439226
TI - Capture and Direct Amplification of DNA on Chitosan Microparticles in a Single
PCR-Optimal Solution.
AB - While nucleic acid amplification tests have great potential as tools for rapid
diagnostics, complicated sample preparation requirements inhibit their use in
near-patient diagnostics and low-resource-setting applications. Recent
advancements in nucleic acid purification have leveraged pH-modulated charge
switching polymers to reduce the number of steps required for sample preparation.
The polycation chitosan (pKa 6.4) has been used to efficiently purify DNA by
binding nucleic acids in acidic buffers and then eluting them at a pH higher than
8.0. Though it is an improvement over conventional methods, this multistep
procedure has not transformed the application of nucleic acid amplification
assays. Here we describe a simpler approach using magnetic chitosan
microparticles that interact with DNA in a manner that has not been reported
before. The microparticles capture DNA at a pH optimal for PCR (8.5) just as
efficiently as at low pH. Importantly, the captured DNA is still accessible by
polymerase, enabling direct amplification from the microparticles. We demonstrate
quantitative PCR from DNA captured on the microparticles, thus eliminating nearly
all of the sample preparation steps. We anticipate that this new streamlined
method for preparing DNA for amplification will greatly expand the diagnostic
applications of nucleic acid amplification tests.
PMID- 26439233
TI - Nutritional management of patients with diabetic peripheral neuropathy with L
methylfolate-methylcobalamin-pyridoxal-5-phosphate: results of a real-world
patient experience trial.
AB - OBJECTIVE: Current therapies for diabetic peripheral neuropathy with pain mask
the painful symptoms while the underlying pathology continues to progress. This
study assessed changes in symptoms and quality of life in patients taking a novel
prescription medical food, L-methylfolate-methylcobalamin-pyridoxal-5-phosphate
(LMF-MC-PP, Metanx ), intended to address the underlying metabolic needs of
patients with diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS:
Between November 2010 and April 2012, patients rated their experiences before and
after using LMF-MC-PP through an automated telephone system that included
symptomatic items from the Neuropathy Total Symptom Score-6 (NTSS-6)
questionnaire and questions related to quality of life and medication
satisfaction. RESULTS: A total of 544 patients participated in the study.
Patients reported a mean reduction of 35% in NTSS-6 scores from after 12 weeks on
LMF-MC-PP. Mean (standard deviation) score was reduced by 1.5 (1.8) at 12 weeks
from a baseline of 4.3 (1.5) (p < 0.05). Patients achieved significant reductions
in self-reported disruptions in work/school activities, social life, and family
life, respectively. Overall pain rating decreased by 32% (p < 0.05). Patients
previously treated with medications reported a 52% improvement in medication
satisfaction (p < 0.05). CONCLUSIONS: In a real-world clinical setting, patients
with diabetic peripheral neuropathy treated with LMF-MC-PP achieved significant
improvements in total symptom score (NTSS-6) and in quality of life and
functioning, together with greater medication satisfaction. A limitation of this
study was the use of a survey instrument to collect data on patient outcomes.
PMID- 26439234
TI - A Pilot Study to Assess the Feasibility of Group Exercise and Animal-Assisted
Therapy in Older Adults.
AB - This pilot study assessed the feasibility of incorporating animal-assisted
therapy teams (ATT) into a 6-week group exercise program for older adults (77 +/-
6 years). Fifteen participants were randomly assigned to an exercise with ATT
(E+ATT; n = 8) or exercise only (E; n = 7) group. Groups exercised 3x/week for 45
min. Feasibility was assessed by three objectives: (1) ATT will not need
extensive preparation beyond their original therapy training; (2) the study will
require minimal cost; and (3) ATT must not impair the effectiveness of the
exercise program. By the study conclusion, all objectives were met. Time and cost
were minimal for ATT, and adherence was 93% and 90% for E+ATT and E,
respectively. There were significant improvements in both groups (p <= .05) for
arm curls, get-up and go, and 6-min walk. The results of this pilot study suggest
that it is feasible to incorporate ATT into group exercise programming for older
adults.
PMID- 26439239
TI - Surface Decoration on Polymeric Gate Dielectrics for Flexible Organic Field
Effect Transistors via Hydroxylation and Subsequent Monolayer Self-Assembly.
AB - A simple photochemical reaction based on confined photocatalytic oxidation (CPO)
treatment and hydrolysis was employed to efficiently convert C-H bonds into C-OH
groups on polymeric material surfaces, followed by investigation of monolayer
self-assembly decoration on polymeric dielectrics via chemical bonding for the
organic field-effect transistors (OFETs) applications. This method is a low
temperature process and has negligible etching effect on polymeric dielectric
layers. Various types of self-assembled monolayers have been tested and
successfully attached onto the hydroxylated polymeric dielectric surfaces through
chemical bonding, ensuring the stability of decorated functional films during the
subsequent device fabrication consisting of solution processing of the polymer
active layer. With the surface decoration of functional groups, both n-type and p
type polymers exhibit enhanced carrier mobilities in the unipolar OFETs. In
addition, enhanced and balanced mobilities are obtained in the ambipolar OFETs
with the blend of polymer semiconductors. The anchored self-assembled monolayers
on the dielectric surfaces dramatically preclude the solvent effect, thus
enabling an improvement of carrier mobility up to 2 orders of magnitude. Our
study opens a way of targeted modifications of polymeric surfaces and related
applications in organic electronics.
PMID- 26439240
TI - Clonidine increases bone resorption in humans.
AB - SUMMARY: Inhibition of sympathetic signaling to bone reduces bone resorption in
rodents. In contrast, we show that pharmacological reduction of the sympathetic
tone increases bone resorption in humans in vivo. This effect does not appear to
be mediated via a direct pharmacological effect on the osteoclast. INTRODUCTION:
Inhibition of sympathetic signaling to bone reduces bone resorption in rodents.
It is uncertain whether a similar role for the sympathetic nervous system exists
in humans. The sympathetic tone can be reduced by clonidine, which acts via alpha
2-adrenergic receptors in the brainstem. Our objective was to determine the
effect of clonidine on bone turnover in humans. METHODS: The acute effect of a
single oral dose of 0.3 mg clonidine on serum bone turnover markers (C-terminal
cross-linking telopeptides of collagen type I (CTx), a marker for bone
resorption, and procollagen type 1 N propeptide (P1NP), a marker for bone
formation) was determined in a randomized crossover design in 12 healthy
volunteers, aged 18-70 years. In addition, we assessed the effect of clonidine on
the number of tartrate-resistant acid phosphatase-positive multinucleated cells
(TRAcP(+) MNCs) and bone resorption. RESULTS: CTx concentrations increased after
clonidine treatment compared to the control condition (p = 0.035). P1NP
concentrations were not affected by clonidine (p = 0.520). In vitro, clonidine
had no effect on the number of TRAcP(+) MNCs (p = 0.513) or on bone resorption (p
= 0.996). CONCLUSIONS: We demonstrated that clonidine increases bone resorption
in humans in vivo. This effect does not appear to be mediated via a direct effect
on the osteoclast.
PMID- 26439241
TI - Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by
regulating skeletal renin-angiotensin system and kallikrein-kinin system in
ovariectomized mice.
AB - SUMMARY: The skeletal renin-angiotensin system contributes to the development of
osteoporosis. The renin inhibitor aliskiren exhibited beneficial effects on
trabecular bone of osteoporotic mice, and this action might be mediated through
angiotensin and bradykinin receptor pathways. This study implies the potential
application of renin inhibitor in the management for postmenopausal osteoporosis.
INTRODUCTION: The skeletal renin-angiotensin system plays key role in the
pathological process of osteoporosis. The present study is designed to elucidate
the effect of renin inhibitor aliskiren on trabecular bone and its potential
action mechanism in ovariectomized (OVX) mice. METHODS: The OVX mice were treated
with low dose (5 mg/kg) or high dose (25 mg/kg) of aliskiren or its vehicle for 8
weeks. The bone turnover markers were measured by ELISA. The structural
parameters of trabecular bone at lumbar vertebra (LV) and distal femoral
metaphysis were measured by micro-CT. The expression of messenger RNA (mRNA) and
protein was studied by RT-PCR and immunoblotting, respectively. RESULTS:
Aliskiren treatment reduced urinary excretion of calcium and serum level of
tartrate-resistant acid phosphatase in OVX mice. The treatment with aliskiren
significantly increased bone volume (BV/TV) and connectivity density (Conn.D) of
trabecular bone at LV-2 and LV-5 as well as dramatically enhanced BV/TV, Conn.D,
bone mineral density (BMD/BV) and decreased bone surface (BS/BV) at the distal
femoral end. Aliskiren significantly down-regulated the expression of
angiotensinogen, angiotensin II (Ang II), Ang II type 1 receptor, bradykinin
receptor (BR)-1, and osteocytic-specific gene sclerostin as well as the
osteoclast-specific genes, including carbonic anhydrase II, matrix
metalloproteinase-9, and cathepsin K. CONCLUSIONS: This study revealed that renin
inhibitor aliskiren exhibited the beneficial effects on trabecular bone of
ovariectomy-induced osteoporotic mice, and the underlying mechanism for this
action might be mediated through Ang II and BR signaling pathways in bone.
PMID- 26439242
TI - Parity and osteoporotic fracture risk in postmenopausal women: a dose-response
meta-analysis of prospective studies.
AB - The present dose-response meta-analysis shows linearly decreased hip fracture
(HF) risk and nonlinearly decreased osteoporotic fracture (OF) risk associated
with increasing number of parity of up to five live births among postmenopausal
women. INTRODUCTION: Epidemiological reports suggest that parity is associated
with reduced OF risk among women. However, these findings are controversial.
Here, we present a meta-analysis of prospective studies of parity in relation to
OF risk. METHODS: We performed systematic searches using Medline and Embase from
January 1, 1966, to December 31, 2014, with limits of language in English and
prospective study design. Relative risks (RRs) and confidence intervals (CIs)
were derived mainly using random-effects models. Categorical, dose-response,
heterogeneity, publication bias, and subgroup analyses were conducted. RESULTS:
We analyzed 10 articles of 19 independent reports from 1966 to 2014, comprising a
total of 217,295 participants and 26,525 cases of OF. Compared to nulliparous
women, the OF and HF risks of parous women with at least one live birth were
reduced by 11 % (95 % confidence interval (CI) 3-19 %; I (2) = 77.1 %, p < 0.001)
and 26 % (95 % CI 17-35 %; I (2) = 19.5 %, p = 0.287), respectively.
Representative nonlinearly and linearly inverse dose-response associations were
found between parity (range of 0-6) and OF risk (p nonlinearity = 0.0163; I (2) =
79.7 %, p < 0.001), and between parity (range of 0-5) and HF risk (p nonlinearity
= 0.054; I (2) = 76.5 %, p < 0.001), respectively. The lowest risk reduction for
OF of 25 % (95 % CI 16-33 %) was observed for five live births. And, the summary
risk reduction for HF was 12 % (95 % CI 9-15 %) for each one increased live
birth. CONCLUSIONS: We found that increasing number of parity is associated with
linearly reduced HF risks among women. The association between parity of six or
more live births and HF risks should be studied further in future.
PMID- 26439243
TI - Effect of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in
patients with coronary artery disease.
AB - Both postprandial hyperlipidemia and hyperinsulinemia have been thought to play
an important role in the development of atherosclerosis, and to be a potent risk
factor for cardiovascular event. To examine effects of glycemic state on
postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery
disease (CAD), a total of 112 consecutive male pati ents with angiographically
confirmed CAD were loaded with a high-fat and high-glucose test meal. CAD
patients were divided into three groups as "non-diabetic", "prediabetic", and
"diabetic" CAD groups. The serum triglyceride (TG) and remnant-like particle
cholesterol (RLP-C) levels at the 6th hour in diabetic CAD group showed
significantly higher than non-diabetic CAD group, and the incremental area under
the curves (iAUCs) of these levels in diabetic CAD group were significantly
greater than non-diabetic CAD group (TG, P = 0.0194; RLP-C, P = 0.0219). There
were no significant differences in the iAUCs of TG or RLP-C between prediabetic
and non-diabetic CAD group. The AUCs of plasma insulin levels or insulin
resistance index (IRI): (AUCs of insulin) * (AUCs of glucose) as the insulin
resistance marker were greater in diabetic CAD group than non-diabetic CAD group
(insulin, P = 0.0373; IRI, P = 0.0228). The AUCs of serum TG or RLP-C levels
showed a correlation with the AUCs of plasma insulin (AUC-TG, r = 0.5437, P <
0.0001; AUC-RLP-C, r = 0.6847, P < 0.0001), and they correlated well with the
insulin resistance index (AUC-TG, r = 0.7724, P < 0.0001; AUC-RLP-C, r = 0.7645,
P < 0.0001). We found that the insulin resistance showed a close relationship
with postprandial hyperlipidemia in CAD patients. Diabetic, but not prediabetic
state, may be a risk for postprandial impaired lipid metabolism in CAD patients.
PMID- 26439245
TI - Erratum to: Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte
Interactions: a Pilot Study in Healthy Subjects.
PMID- 26439244
TI - Estrus response and fertility of Menz and crossbred ewes to single prostaglandin
injection protocol.
AB - Natural lambing in sheep in Ethiopia occurs throughout the year in a scattered
manner negatively affecting survival and growth rates of the lambs born during
the unfavorable season of the year. Thus, controlling the time of mating
artificially using exogenous source of hormones is considered as one of the ways
to mitigated problems related to haphazard lambing. To this end, an experiment
was conducted to evaluate efficacy of prostaglandin-based estrus synchronization
protocol in local and crossbred ewes. A total of 160 ewes (80 local and 80
crossbreds) which lambed at least once and aged 3-5 years were used. Lutalyse(r)
(dinoprost tromethamine sterile solution equivalent to 5 mg dinoprost per ml) and
its analog, Synchromate(r) (cloprostenol sodium equivalent to 0.250 mg
cloprostenol per ml), were tested at different doses. The treatments used were
intramuscular injection of (1) 2.50 ml of Lutalyse(r) (12.5 mg dinoprost
tromethamine), (2) 2 ml of Lutalyse(r) (10.0 mg dinoprost tromethamine), (3) 1 ml
of Synchromate(r) (0.25 mg of cloprostenol Sodium), and (4) 0.8 ml of
Synchromate(r) (0.20 mg of cloprostenol Sodium). Forty ewes (20 local and 20
crossbreds) were allocated per treatment. Following injection of the respective
hormones, rams of known fertility were introduced into the flock for the duration
of 96 h at the ratio of one ram to 10 ewes. All estrus synchronization protocols
except treatment 4 (0.8 ml of Synchromate(r)) induced estrus (heat) in majority
(55-65%) of local and crossbred ewes within 96 h post-hormone injection. The time
interval from hormone administration to onset of estrus was also more or less
similar for all treatment groups except for treatment group 4 which showed heat
quicker. The highest lambing rate was recorded in local ewes (84.62% (11/13)
treated with 2.5 ml of Lutalyse(r), whereas the least was obtained in crossbreds
(33.33% (3/9) treated with 0.8 ml Synchromate(r). In conclusion, even though 2.5
ml and 2 ml of Lutalyse(r) or 1 ml of Synchromate(r) were able to induce heat in
majority of local and crossbred ewes, the highest lambing percentage was obtained
from ewes treated with 2.5 ml of Lutalyse(r). Therefore, the use of 2.5 ml
Lutalyse(r) is recommended to synchronize estrus in local and crossbred ewes
under Ethiopian smallholder sheep production system for the benefit of improved
lambing rate.
PMID- 26439246
TI - Raloxifene Inhibits NF-kB Pathway and Potentiates Anti-Tumour Activity of
Cisplatin with Simultaneous Reduction in its Nephrotoxictiy.
AB - Cisplatin induced nephrotoxicity is the chief obstacle in the use of cisplatin as
chemotherapeutic agent. However, it remains as most widely employed anticancer
agent to treat various solid tumours like head-neck, testicular, ovarian and
mammary gland cancer. Raloxifene is claimed to be potent anti-inflammatory as
well as anti-cancer agent. The present study was carried out to explore the
effect of pre-treatment of raloxifene on cisplatin induced nephrotoxicity and its
anti-tumour activity in 7, 12 dimethyl benz [a] anthracene induced mammary tumour
in animal model. Renal damage was accessed by measuring serum level of
creatinine, blood urea nitrogen and albumin whereas systemic inflammation was
accessed by measuring level of pro-inflammatory cytokines like tumour necrosis
factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 10 (IL-10) and
nuclear factor kappa B (NFkappaB). Moreover, assessment of tumour reduction was
done by measuring tumour volume and percentage tumour reduction. A single dose of
cisplatin (7.5 mg/kg) resulted in significant increase in serum creatinine, blood
urea nitrogen, NF-kB, TNF-alpha and IL-6 levels along with decrease in albumin
and IL-10 levels. However, there were no significant changes in raloxifene (8
mg/kg) treated group. Pre-treatment of raloxifene (8 mg/kg) caused marked
decrease in serum creatinine, blood urea nitrogen, TNF-alpha and IL-6 levels
whereas increase in albumin and IL-10 levels. However, pre-treatment of
raloxifene showed maximum tumour reduction as compared to cisplatin and
raloxifene treated groups. The present study demonstrates that raloxifene
potentiates anti-tumour activity of cisplatin with simultaneous reduction in its
nephrotoxicity, and this effect is attributed to its direct anti-inflammatory
activity.
PMID- 26439247
TI - Entransia and Hormidiella, sister lineages of Klebsormidium (Streptophyta),
respond differently to light, temperature, and desiccation stress.
AB - The green-algal class Klebsormidiophyceae (Streptophyta), which occurs worldwide,
comprises the genera Klebsormidium, Interfilum, Entransia, and Hormidiella.
Ecophysiological research has so far focused on the first two genera because they
are abundant in biological soil crust communities. The present study investigated
the photosynthetic performances of Hormidiella attenuata and two strains of
Entransia fimbriata under light, temperature, and desiccation stress. Their
ultrastructure was compared using transmission electron microscopy. The two
Entransia strains showed similar physiological responses. They used light more
efficiently than Hormidiella, as indicated by higher oxygen production and
relative electron transport rate under low light conditions, lower light
saturation and compensation points, and higher maximum oxygen production during
light saturation. Their requirement for low light levels explains the restriction
of Entransia to dim limnetic habitats. In contrast, Hormidiella, which prefers
drier soil habitats, responded to light gradients similarly to other aero
terrestrial green algae. Compared to Entransia, Hormidiella was less affected by
short-term desiccation, and rehydration allowed full recovery of the
photosynthetic performance. Nevertheless, both strains of Entransia coped with
low water availability better than other freshwater algae. Photosynthetic oxygen
production in relation to respiratory consumption was higher in low temperatures
(Entransia: 5 degrees C, Hormidiella: 10 degrees C) and the ratio decreased
with increasing temperatures. Hormidiella exhibited conspicuous triangular spaces
in the cell wall corners, which were filled either with undulating cell wall
material or with various inclusions. These structures are commonly seen in
various members of Klebsormidiophyceae. The data revealed significant differences
between Hormidiella and Entransia, but appropriate adaptations to their
respective habitats.
PMID- 26439248
TI - Monocyte/HDL-cholesterol ratio predicts the definite stent thrombosis after
primary percutaneous coronary intervention for ST-segment elevation myocardial
infarction.
AB - AIM: We investigated the predictive value of monocyte count to HDL ratio (M/H
ratio) for stent thrombosis (ST) in ST elevation myocardial infarction (STEMI).
PATIENTS & METHODS: 1170 STEMI patients treated with primary PCI were followed-up
for a median of 37.2 months. RESULTS: During follow-up, 112 patients were
diagnosed as 'definite' ST. The rate of ST was significantly highest in the third
M/H ratio tertile. In Cox regression analysis, adjusted for other factors, having
an M/H ratio in third tertile had a 2.2-fold increased risk of ST. Kaplan-Meier
analysis revealed the higher occurrence of ST in the third tertile compared with
others (p <0.001). CONCLUSION: M/H ratio as a novel marker of inflammation seemed
to be an independent predictor of ST in STEMI patients.
PMID- 26439249
TI - Dynamic Kinetic Resolution of Phthalides via Asymmetric Transfer Hydrogenation: A
Strategy Constructs 1,3-Distereocentered 3-(2-Hydroxy-2-arylethyl)isobenzofuran
1(3H)-one.
AB - Dynamic kinetic resolution of phthalides through asymmetric transfer
hydrogenation for the construction of 3-(2-hydroxy-2-arylethyl)isobenzofuran
1(3H)-one with 1,3-distereocenters has been developed. This procedure is carried
out under a mild condition at 40 degrees C catalyzed with RuCl[(S,S)
TsDPEN](mesitylene) using HCOOH/Et3N (5:2) as a hydrogen source. A variety of
phthalides are smoothly transferred to provide optically pure phthalides with
high yields, excellent enantioselectivities, and acceptable diastereomeric
ratios.
PMID- 26439250
TI - Adolescents' perception of the severity of binge eating disorder: a population
based study.
AB - BACKGROUND: Binge eating disorder (BED) is relatively common in young people and
is associated with marked impairment in physical and mental health. AIMS: We
examined perceptions of the severity of BED in a population-based sample of
adolescents. METHODS: Male (n = 531) and female (n = 1135) adolescents recruited
from 12 Australian schools completed a survey that featured a vignette of a
fictional female school student suffering from BED followed by a series of
questions addressing perceptions of severity. RESULTS: Approximately half of
participants agreed or strongly agreed that BED is a serious problem (male:
52.0%; female: 63.2%) requiring professional treatment (male: 48.2%; female:
54.5%). Approximately one-third of boys (30.7%) believed that BED is primarily a
problem of "lack of will power/self-control", whereas one in five girls (19.3%)
held this view. Less than half of participants (male: 42.7%; female: 44.1%)
believed that someone with BED would be deserving of sympathy. CONCLUSION: The
findings suggest that many adolescents, boys in particular, do not consider BED
to be a serious mental health problem and believe that individuals with BED lack
will-power and/or are undeserving of sympathy. Awareness and understanding of BED
may need to be addressed in school-based mental health promotion programs.
PMID- 26439251
TI - Platinum-Catalyzed, Terminal-Selective C(sp(3))-H Oxidation of Aliphatic Amines.
AB - This Communication describes the terminal-selective, Pt-catalyzed C(sp(3))-H
oxidation of aliphatic amines without the requirement for directing groups. CuCl2
is employed as a stoichiometric oxidant, and the reactions proceed in high yield
at Pt loadings as low as 1 mol%. These transformations are conducted in the
presence of sulfuric acid, which reacts with the amine substrates in situ to form
ammonium salts. We propose that protonation of the amine serves at least three
important roles: (i) it renders the substrates soluble in the aqueous reaction
medium; (ii) it limits binding of the amine nitrogen to Pt or Cu; and (iii) it
electronically deactivates the C-H bonds proximal to the nitrogen center. We
demonstrate that this strategy is effective for the terminal-selective C(sp(3))-H
oxidation of a variety of primary, secondary, and tertiary amines.
PMID- 26439258
TI - A Generative Statistical Algorithm for Automatic Detection of Complex Postures.
AB - This paper presents a method for automated detection of complex (non-self
avoiding) postures of the nematode Caenorhabditis elegans and its application to
analyses of locomotion defects. Our approach is based on progressively detailed
statistical models that enable detection of the head and the body even in cases
of severe coilers, where data from traditional trackers is limited. We restrict
the input available to the algorithm to a single digitized frame, such that
manual initialization is not required and the detection problem becomes
embarrassingly parallel. Consequently, the proposed algorithm does not propagate
detection errors and naturally integrates in a "big data" workflow used for large
scale analyses. Using this framework, we analyzed the dynamics of postures and
locomotion of wild-type animals and mutants that exhibit severe coiling
phenotypes. Our approach can readily be extended to additional automated tracking
tasks such as tracking pairs of animals (e.g., for mating assays) or different
species.
PMID- 26439259
TI - Concurrent Visualization of Acoustic Radiation Force Displacement and Shear Wave
Propagation with 7T MRI.
AB - Manual palpation is a common and very informative diagnostic tool based on
estimation of changes in the stiffness of tissues that result from pathology. In
the case of a small lesion or a lesion that is located deep within the body, it
is difficult for changes in mechanical properties of tissue to be detected or
evaluated via palpation. Furthermore, palpation is non-quantitative and cannot be
used to localize the lesion. Magnetic Resonance-guided Focused Ultrasound
(MRgFUS) can also be used to evaluate the properties of biological tissues non
invasively. In this study, an MRgFUS system combines high field (7T) MR and 3 MHz
focused ultrasound to provide high resolution MR imaging and a small ultrasonic
interrogation region (~0.5 x 0.5 x 2 mm), as compared with current clinical
systems. MR-Acoustic Radiation Force Imaging (MR-ARFI) provides a reliable and
efficient method for beam localization by detecting micron-scale displacements
induced by ultrasound mechanical forces. The first aim of this study is to
develop a sequence that can concurrently quantify acoustic radiation force
displacements and image the resulting transient shear wave. Our motivation in
combining these two measurements is to develop a technique that can rapidly
provide both ARFI and shear wave velocity estimation data, making it suitable for
use in interventional radiology. Secondly, we validate this sequence in vivo by
estimating the displacement before and after high intensity focused ultrasound
(HIFU) ablation, and we validate the shear wave velocity in vitro using tissue
mimicking gelatin and tofu phantoms. Such rapid acquisitions are especially
useful in interventional radiology applications where minimizing scan time is
highly desirable.
PMID- 26439260
TI - Analyses of Twelve New Whole Genome Sequences of Cassava Brown Streak Viruses and
Ugandan Cassava Brown Streak Viruses from East Africa: Diversity, Supercomputing
and Evidence for Further Speciation.
AB - Cassava brown streak disease is caused by two devastating viruses, Cassava brown
streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV) which are
frequently found infecting cassava, one of sub-Saharan Africa's most important
staple food crops. Each year these viruses cause losses of up to $100 million USD
and can leave entire families without their primary food source, for an entire
year. Twelve new whole genomes, including seven of CBSV and five of UCBSV were
uncovered in this research, doubling the genomic sequences available in the
public domain for these viruses. These new sequences disprove the assumption that
the viruses are limited by agro-ecological zones, show that current diagnostic
primers are insufficient to provide confident diagnosis of these viruses and give
rise to the possibility that there may be as many as four distinct species of
virus. Utilizing NGS sequencing technologies and proper phylogenetic practices
will rapidly increase the solution to sustainable cassava production.
PMID- 26439262
TI - New Insights into Polychaete Traces and Fecal Pellets: Another Complex
Ichnotaxon?
AB - Neoichnological observations help refine paleoichnological records. The present
study reports extensive observations on the distribution, morphology, occurrence
and association of burrows and fecal pellets of the polychaete Nereis
diversicolor in the Kundalika Estuary on the west coast of India. Our holistic
study of these modern-day traces suggests it to be a complex trace arising from
domichnial, fodinichnial and possibly pascichnial behavior of polychaetes. The
study for the first time reports extensive fecal pellet production, distribution
and their preservation as thick stacks in modern estuarine environment. These
observations testify the fossilization potential of pellets and provide an
explanation to their origin in the geological record. Their occurrence as strings
associated with mounds not only suggests pascichnial behaviour of polychaetes but
also allows the assignment of post-Paleozoic Tomaculum to the activity of
polychaete worms. The production of fecal pellets in such large quantities plays
a major role in increasing the average grain size of the substrate of these
estuarine tidal flats, thereby improving aeration within the substrate.
PMID- 26439261
TI - The Magnitude of Peripheral Muscle Fatigue Induced by High and Low Intensity
Single-Joint Exercise Does Not Lead to Central Motor Output Reductions in
Resistance Trained Men.
AB - PURPOSE: To examine quadriceps muscle fatigue and central motor output during
fatiguing single joint exercise at 40% and 80% maximal torque output in
resistance trained men. METHOD: Ten resistance trained men performed fatiguing
isometric knee extensor exercise at 40% and 80% of maximal torque output. Maximal
torque, rate of torque development, and measures of central motor output and
peripheral muscle fatigue were recorded at two matched volumes of exercise, and
after a final contraction performed to exhaustion. Central motor output was
quantified from changes in voluntary activation, normalized surface
electromyograms (EMG), and V-waves. Quadriceps muscle fatigue was assessed from
changes in the size and shape of the resting potentiated twitch (Q.(pot.tw)).
Central motor output during the exercise protocols was estimated from EMG and
interpolated twitches applied during the task (VA(sub)). RESULTS: Greater
reductions in maximal torque and rate of torque development were observed during
the 40% protocol (p<0.05). Maximal central motor output did not change for either
protocol. For the 40% protocol reductions from pre-exercise in rate and amplitude
variables calculated from the Q.(pot.tw) between 66.2 to 70.8% (p<0.001) exceeded
those observed during the 80% protocol (p<0.01). V-waves only declined during the
80% protocol between 56.8 +/- 35.8% to 53.6 +/- 37.4% (p<0.05). At the end of the
final 80% contraction VA(sub) had increased from 91.2 +/- 6.2% to 94.9 +/- 4.7%
(p = 0.005), but a greater increase was observed during the 40% contraction where
VA(sub) had increased from 67.1 +/- 6.1% to 88.9 +/- 9.6% (p<0.001). CONCLUSION:
Maximal central motor output in resistance trained men is well preserved despite
varying levels of peripheral muscle fatigue. Upregulated central motor output
during the 40% contraction protocol appeared to elicit greater peripheral
fatigue. V-waves declines during the 80% protocol suggest intensity dependent
modulation of the Ia afferent pathway.
PMID- 26439263
TI - Seventy Years of Asthma in Italy: Age, Period and Cohort Effects on Incidence and
Remission of Self-Reported Asthma from 1940 to 2010.
AB - BACKGROUND: It is well known that asthma prevalence has been increasing all over
the world in the last decades. However, few data are available on temporal trends
of incidence and remission of asthma. OBJECTIVE: To evaluate the rates of asthma
incidence and remission in Italy from 1940 to 2010. METHODS: The subjects were
randomly sampled from the general Italian population between 1991 and 2010 in the
three population-based multicentre studies: ECRHS, ISAYA, and GEIRD. Individual
information on the history of asthma (age at onset, age at the last attack, use
of drugs for asthma control, co-presence of hay-fever) was collected on 35,495
subjects aged 20-84 and born between 1925-1989. Temporal changes in rates of
asthma incidence and remission in relation to age, birth cohort and calendar
period (APC) were modelled using Poisson regression and APC models. RESULTS: The
average yearly rate of asthma incidence was 2.6/1000 (3,297 new cases among
1,263,885 person-years). The incidence rates have been linearly increasing, with
a percentage increase of +3.9% (95%CI: 3.1-4.5), from 1940 up to the year 1995,
when the rates begun to level off. The stabilization of asthma incidence was
mainly due to a decrease in the rates of atopic asthma after 1995, while non
atopic asthma has continued to increase. The overall rate of remission was
43.2/1000person-years, and it did not vary significantly across generations, but
was associated with atopy, age at asthma onset and duration of the disease.
CONCLUSIONS: After 50 years of a continuous upward trend, the rates of asthma
incidence underwent a substantial stabilization in the late 90s. Despite
remarkable improvements in the treatment of asthma, the rate of remission did not
change significantly in the last seventy years. Some caveats are required in
interpreting our results, given that our estimates are based on self-reported
events that could be affected by the recall bias.
PMID- 26439265
TI - The Value of Being Wrong: Intermittent Feedback Delivery Alters the Striatal
Response to Negative Feedback.
AB - Whereas positive feedback is both rewarding and informative, negative feedback
can be construed as either punishing (because it is indicative of poor
performance) or informative (because it may lead to goal attainment). In this
neuroimaging experiment, we highlighted the informational value of negative
feedback by intermixing trials with and without feedback. When performance
feedback is expected, positive feedback triggers an increase in striatal
activity, whereas negative feedback elicits a decrease in striatal activity. We
predicted that, in contrast, when feedback receipt is unpredictable, the striatal
response to negative feedback would increase. Participants performed a paired
associate learning task during fMRI scanning. In one condition ("blocked
feedback"), the receipt of feedback was predictable--participants knew whether or
not they would receive feedback for their responses. In another condition ("mixed
feedback"), the receipt of feedback was unpredictable--on a random 50% of trials,
participants received feedback, and they otherwise received no feedback. Negative
feedback in the mixed feedback condition elicited more striatal activity than
negative feedback in the blocked feedback condition. In contrast, feedback
omission evoked more striatal activity when feedback delivery was expected,
compared to when it was unpredictable. This pattern emerged from an increase in
caudate activity in response to negative feedback in the mixed feedback condition
and a decrease in ventral striatal activity in response to no feedback in this
condition. These results suggest that, by emphasizing the informational value of
negative feedback, an unpredictable feedback context alters the striatal response
to negative feedback and to the omission of feedback.
PMID- 26439264
TI - Contrasting Effects of the Cytotoxic Anticancer Drug Gemcitabine and the EGFR
Tyrosine Kinase Inhibitor Gefitinib on NK Cell-Mediated Cytotoxicity via
Regulation of NKG2D Ligand in Non-Small-Cell Lung Cancer Cells.
AB - INTRODUCTION: Several cytotoxic anticancer drugs inhibit DNA replication and/or
mitosis, while EGFR tyrosine kinase inhibitors inactivate EGFR signalling in
cancer cell. Both types of anticancer drugs improve the overall survival of the
patients with non-small-cell lung cancer (NSCLC), although tumors often become
refractory to this treatment. Despite several mechanisms by which the tumors
become resistant having been described the effect of these compounds on anti
tumor immunity remains largely unknown. METHODS: This study examines the effect
of the cytotoxic drug Gemcitabine and the EGFR tyrosine kinase inhibitor
Gefitinib on the expression of NK group 2 member D (NKG2D) ligands as well as the
sensitivity of NSCLC cells to the NK-mediated lysis. RESULTS: We demonstrate that
Gemcitabine treatment leads to an enhanced expression, while Gefitinib
downregulated the expression of molecules that act as key ligands for the
activating receptor NKG2D and promote NK cell-mediated recognition and cytolysis.
Gemcitabine activated ATM and ATM- and Rad-3-related protein kinase (ATR)
pathways. The Gemcitabine-induced phosphorylation of ATM as well as the
upregulation of the NKG2D ligand expression could be blocked by an ATM-ATR
inhibitor. In contrast, Gefitinib attenuated NKG2D ligand expression. Silencing
EGFR using siRNA or addition of the PI3K inhibitor resulted in downregulation of
NKG2D ligands. The observations suggest that the EGFR/PI3K pathway also regulates
the expression of NKG2D ligands. Additionally, we showed that both ATM-ATR and
EGFR regulate MICA/B via miR20a. CONCLUSION: In keeping with the effect on NKG2D
expression, Gemcitabine enhanced NK cell-mediated cytotoxicity while Gefitinib
attenuated NK cell killing in NSCLC cells.
PMID- 26439266
TI - The Processing of Attended and Predicted Sounds in Time.
AB - Neural responses to an attended event are typically enhanced relative to those
from an unattended one (attention enhancement). Conversely, neural responses to a
predicted event are typically reduced relative to those from an unpredicted one
(prediction suppression). What remains to be established is what happens with
attended and predicted events. To examine the interaction between attention and
prediction, we combined two robust paradigms developed for studying attention and
prediction effects on ERPs into an orthogonal design. Participants were presented
with sounds in attended or unattended intervals with onsets that were either
predicted by a moving visual cue or unpredicted (no cue was provided). We
demonstrated an N1 enhancement effect for attended sounds and an N1 suppression
effect for predicted sounds; furthermore, an interaction between these effects
was found that emerged early in the N1 (50-95 msec), indicating that attention
enhancement only occurred when the sound was unpredicted. This pattern of results
can be explained by the precision of the predictive cue that reduces the need for
attention selection in the attended and predicted condition.
PMID- 26439267
TI - Prefrontal Goal Codes Emerge as Latent States in Probabilistic Value Learning.
AB - The prefrontal cortex (PFC) supports goal-directed actions and exerts cognitive
control over behavior, but the underlying coding and mechanism are heavily
debated. We present evidence for the role of goal coding in PFC from two
converging perspectives: computational modeling and neuronal-level analysis of
monkey data. We show that neural representations of prospective goals emerge by
combining a categorization process that extracts relevant behavioral abstractions
from the input data and a reward-driven process that selects candidate categories
depending on their adaptive value; both forms of learning have a plausible neural
implementation in PFC. Our analyses demonstrate a fundamental principle: goal
coding represents an efficient solution to cognitive control problems, analogous
to efficient coding principles in other (e.g., visual) brain areas. The novel
analytical-computational approach is of general interest because it applies to a
variety of neurophysiological studies.
PMID- 26439268
TI - Asymmetric Processing of Numerical and Nonnumerical Magnitudes in the Brain: An
fMRI Study.
AB - It is well established that, when comparing nonsymbolic magnitudes (e.g., dot
arrays), adults can use both numerical (i.e., the number of items) and
nonnumerical (density, total surface areas, etc.) magnitudes. It is less clear
which of these magnitudes is more salient or processed more automatically. In
this fMRI study, we used a nonsymbolic comparison task to ask if different brain
areas are responsible for the automatic processing of numerical and nonnumerical
magnitudes, when participants were instructed to attend to either the numerical
or the nonnumerical magnitudes of the same stimuli. An interaction of task
(numerical vs. nonnumerical) and congruity (congruent vs. incongruent) was found
in the right TPJ. Specifically, this brain region was more strongly activated
during numerical processing when the nonnumerical magnitudes were negatively
correlated with numerosity (incongruent trials). In contrast, such an
interference effect was not evident during nonnumerical processing when the task
irrelevant numerical magnitude was incongruent. In view of the role of the right
TPJ in the control of stimulus-driven attention, we argue that these data
demonstrate that the processing of nonnumerical magnitudes is more automatic than
that of numerical magnitudes and that, therefore, the influence of numerical and
nonnumerical variables on each other is asymmetrical.
PMID- 26439269
TI - The Role of the Frontal and Parietal Cortex in Proactive and Reactive Inhibitory
Control: A Transcranial Direct Current Stimulation Study.
AB - Mounting evidence suggests that response inhibition involves both proactive and
reactive inhibitory control, yet its underlying neural mechanisms remain elusive.
In particular, the roles of the right inferior frontal gyrus (IFG) and inferior
parietal lobe (IPL) in proactive and reactive inhibitory control are still under
debate. This study aimed at examining the causal role of the right IFG and IPL in
proactive and reactive inhibitory control, using transcranial direct current
stimulation (tDCS) and the stop signal task. Twenty-two participants completed
three sessions of the stop signal task, under anodal tDCS in the right IFG, the
right IPL, or the primary visual cortex (VC; 1.5 mA for 15 min), respectively.
The VC stimulation served as the active control condition. The tDCS effect for
each condition was calculated as the difference between pre- and post-tDCS
performance. Proactive control was indexed by the RT increase for go trials (or
preparatory cost), and reactive control by the stop signal RT. Compared to the VC
stimulation, anodal stimulation of the right IFG, but not that of the IPL,
facilitated both proactive and reactive control. However, the facilitation of
reactive control was not mediated by the facilitation of proactive control.
Furthermore, tDCS did not affect the intraindividual variability in go RT. These
results suggest a causal role of the right IFG, but not the right IPL, in both
reactive and proactive inhibitory control.
PMID- 26439271
TI - Timing Matters? Learning of Complex Spatiotemporal Sequences in Left-hemisphere
Stroke Patients.
AB - During rehabilitation after stroke motor sequence learning is of particular
importance because considerable effort is devoted to (re)acquiring lost motor
skills. Previous studies suggest that implicit motor sequence learning is
preserved in stroke patients but were restricted to the spatial dimension,
although the timing of single action components is as important as their spatial
order. As the left parietal cortex is known to play a critical role in implicit
timing and spatiotemporal integration, in this study we applied an adapted
version of the SRT task designed to assess both spatial (different stimulus
locations) and temporal (different response-stimulus intervals) aspects of motor
learning to 24 right-handed patients with a single left-hemisphere (LH) stroke
and 24 age-matched healthy controls. Implicit retrieval of sequence knowledge was
tested both at Day 1 and after 24 hr (Day 2). Additionally, voxel-based lesion
symptom mapping was used to investigate the neurobiological substrates of the
behavioral effects. Although LH stroke patients showed a combined spatiotemporal
learning effect that was comparable to that observed in controls, LH stroke
patients did not show learning effects for the learning probes in which only one
type of sequence information was maintained whereas the other one was randomized.
Particularly on Day 2, patients showed significantly smaller learning scores for
these two learning probes than controls. Voxel-based lesion symptom mapping
analyses revealed for all learning probes that diminished learning scores on Day
2 were associated with lesions of the striatum. This might be attributed to its
role in motor chunking and offline consolidation as group differences occurred on
Day 2 only. The current results suggest that LH stroke patients rely on
multimodal information (here: temporal and spatial information) when retrieving
motor sequence knowledge and are very sensitive to any disruption of the learnt
sequence information as they seem to build very rigid chunks preventing them from
forming independent spatial and temporal sequence representations.
PMID- 26439270
TI - Biased Competition during Long-term Memory Formation.
AB - A key task for the brain is to determine which pieces of information are worth
storing in memory. To build a more complete representation of the environment,
memory systems may prioritize new information that has not already been stored.
Here, we propose a mechanism that supports this preferential encoding of new
information, whereby prior experience attenuates neural activity for old
information that is competing for processing. We evaluated this hypothesis with
fMRI by presenting a series of novel stimuli concurrently with repeated stimuli
at different spatial locations in Experiment 1 and from different visual
categories (i.e., faces and scenes) in Experiment 2. Subsequent memory for the
novel stimuli could be predicted from the reduction in activity in ventral
temporal cortex for the accompanying repeated stimuli. This relationship was
eliminated in control conditions where the competition during encoding came from
another novel stimulus. These findings reveal how prior experience adaptively
guides learning toward new aspects of the environment.
PMID- 26439272
TI - Cortical Thickness in Fusiform Face Area Predicts Face and Object Recognition
Performance.
AB - The fusiform face area (FFA) is defined by its selectivity for faces. Several
studies have shown that the response of FFA to nonface objects can predict
behavioral performance for these objects. However, one possible account is that
experts pay more attention to objects in their domain of expertise, driving
signals up. Here, we show an effect of expertise with nonface objects in FFA that
cannot be explained by differential attention to objects of expertise. We explore
the relationship between cortical thickness of FFA and face and object
recognition using the Cambridge Face Memory Test and Vanderbilt Expertise Test,
respectively. We measured cortical thickness in functionally defined regions in a
group of men who evidenced functional expertise effects for cars in FFA.
Performance with faces and objects together accounted for approximately 40% of
the variance in cortical thickness of several FFA patches. Whereas participants
with a thicker FFA cortex performed better with vehicles, those with a thinner
FFA cortex performed better with faces and living objects. The results point to a
domain-general role of FFA in object perception and reveal an interesting double
dissociation that does not contrast faces and objects but rather living and
nonliving objects.
PMID- 26439274
TI - Restricted antibody response to Bordetella pertussis filamentous hemagglutinin
induced by whole-cell and acellular pertussis vaccines.
AB - BACKGROUND: Filamentous hemagglutinin (FHA) is a principal virulence factor, an
important immunogenic antigen of Bordetella pertussis, and a major component of
many acellular pertussis vaccines. In the present study, the human antibody
response to different regions of FHA was determined in healthy children and
adults vaccinated with either whole-cell or acellular pertussis vaccines.
METHODS: To define the immunodominant regions of FHA, four overlapping
recombinant fragments were expressed and produced in Escherichia coli and then
purified by His-tagged based affinity chromatography. Two groups comprising
healthy preschool children (n = 50) and adults (n = 26) were vaccinated with a
single dose of commercial whole-cell and acellular DTaP vaccines, respectively.
An antigen-based ELISA was applied to measure serum levels of anti-FHA antibody
to both native and recombinant proteins in vaccinated volunteers. RESULTS: In
both groups of vaccinated individuals, the anti-FHA antibody response was mainly
directed against epitopes located within a fragment of FHA spanning amino acid
residues 1877-2250 of the mature FHA molecule (p < 0.001). No or little antibody
was detected against the other recombinant segments of FHA. CONCLUSION: Our
results suggest that the human antibody response to FHA is directed to an
immunodominant region located within residues 1877-2250 of the FHA molecule.
Characterization and epitope mapping of the major components of acellular
pertussis vaccine and future modifications in vaccine formulation may improve its
efficacy and protectivity.
PMID- 26439275
TI - Ultrasound-Guided Versus Wire-Guided Breast-Conserving Surgery for Nonpalpable
Breast Cancer.
AB - PURPOSE: To determine the efficacy of ultrasound (US)-guided excision of
nonpalpable breast cancer and compare it to standard wire-guided breast
conserving surgery (BCS). METHODS: One hundred fifty-eight women with nonpalpable
breast cancer who underwent BCS were retrospectively studied. Positive surgical
margins and reexcision rates were investigated. RESULTS: Of the total cohort, 68
patients were treated with wire-guided and 90 with US-guided tumor excision. The
tumor and patient characteristics were similar in the 2 groups; 13.2% and 12.2%
of patients in the wire-guided and US-guided groups, respectively, had positive
margins. Patient age, menopausal status, tumor size, histologic type, and
histologic grade were associated with increased risk of positive margins. The
shave margins were reexcised at the time of original operation more often by wire
guided localization (26.5%) than in the US-guided group (10.0%) (P = .010). The
surgeon was able to identify correctly the problematic margin in 100% via
intraoperative US and in only 27.8% when the wire-guided surgery was used (P <
.001). The reexcision rate by a second operation was similar in 2 groups (P =
.798). Eight (11.8%) of 68 patients in the wire-guided group and 9 (10.0%) of 90
patients in the US-guided underwent a second operation. CONCLUSION: US-guided BCS
is as effective and safe as standard wire-guided excision of nonpalpable breast
tumors.
PMID- 26439276
TI - Ultra-high voltage electron microscopy of primitive algae illuminates 3D
ultrastructures of the first photosynthetic eukaryote.
AB - A heterotrophic organism 1-2 billion years ago enslaved a cyanobacterium to
become the first photosynthetic eukaryote, and has diverged globally. The primary
phototrophs, glaucophytes, are thought to retain ancestral features of the first
photosynthetic eukaryote, but examining the protoplast ultrastructure has
previously been problematic in the coccoid glaucophyte Glaucocystis due to its
thick cell wall. Here, we examined the three-dimensional (3D) ultrastructure in
two divergent species of Glaucocystis using ultra-high voltage electron
microscopy. Three-dimensional modelling of Glaucocystis cells using electron
tomography clearly showed that numerous, leaflet-like flattened vesicles are
distributed throughout the protoplast periphery just underneath a single-layered
plasma membrane. This 3D feature is essentially identical to that of another
glaucophyte genus Cyanophora, as well as the secondary phototrophs in Alveolata.
Thus, the common ancestor of glaucophytes and/or the first photosynthetic
eukaryote may have shown similar 3D structures.
PMID- 26439277
TI - Decade in review-dementia: a decade of discovery and disappointment in dementia
research.
PMID- 26439279
TI - Borderline Lepromatous Leprosy: Cutaneous Manifestation and Type 1 Reversal
Reaction.
PMID- 26439278
TI - Aberrant intra- and inter-network connectivity architectures in Alzheimer's
disease and mild cognitive impairment.
AB - Alzheimer's disease (AD) patients and those with high-risk mild cognitive
impairment are increasingly considered to have dysfunction syndromes. Large-scale
network studies based on neuroimaging techniques may provide additional insight
into AD pathophysiology. The aim of the present study is to evaluate the impaired
network functional connectivity with the disease progression. For this purpose,
we explored altered functional connectivities based on previously well-defined
brain areas that comprise the five key functional systems [the default mode
network (DMN), dorsal attention network (DAN), control network (CON), salience
network (SAL), sensorimotor network (SMN)] in 35 with AD and 27 with mild
cognitive impairment (MCI) subjects, compared with 27 normal cognitive subjects.
Based on three levels of analysis, we found that intra- and inter-network
connectivity were impaired in AD. Importantly, the interaction between the
sensorimotor and attention functions was first attacked at the MCI stage and then
extended to the key functional systems in the AD individuals. Lower cognitive
ability (lower MMSE scores) was significantly associated with greater reductions
in intra- and inter-network connectivity across all patient groups. These
profiles indicate that aberrant intra- and inter-network dysfunctions might be
potential biomarkers or predictors of AD progression and provide new insight into
AD pathophysiology.
PMID- 26439280
TI - Mechanically activated switching of Si-based single-molecule junction as imaged
with three-dimensional dynamic probe.
AB - Understanding and extracting the full functions of single-molecule
characteristics are key factors in the development of future device technologies,
as well as in basic research on molecular electronics. Here we report a new
methodology for realizing a three-dimensional (3D) dynamic probe of single
molecule conductance, which enables the elaborate 3D analysis of the
conformational effect on molecular electronics, by the formation of a Si/single
molecule/Si structure using scanning tunnelling microscopy (STM). The formation
of robust covalent bonds between a molecule and Si electrodes, together with STM
related techniques, enables the stable and repeated control of the conformational
modulation of the molecule. By 3D imaging of the conformational effect on a 1,4
diethynylbenzene molecule, a binary change in conductance with hysteresis is
observed for the first time, which is considered to originate from a mechanically
activated conformational change.
PMID- 26439282
TI - Carbon nanotubes-gold nanohybrid as potent electrocatalyst for oxygen reduction
in alkaline media.
AB - A carbon nanotube-gold nanohybrid was used as catalyst for the reduction of
molecular oxygen in acidic and alkaline media, the relevant cathode reaction in
fuel cells. In alkaline medium, the nanohybrid exhibits excellent activity with a
dominant 4e(-) reduction of O2 and low overpotential requirement compared to
previously reported nano-gold materials. This property is linked to its
capability to efficiently mediate HO2(-) dismutation.
PMID- 26439281
TI - Mechanism of C-Terminal Fragments of Amyloid beta-Protein as Abeta Inhibitors: Do
C-Terminal Interactions Play a Key Role in Their Inhibitory Activity?
AB - Targeting the early oligomerization of amyloid beta protein (Abeta) is a
promising therapeutic strategy for Alzheimer's disease (AD). Recently, certain C
terminal fragments (CTFs) derived from Abeta42 were shown to be potent inhibitors
of Abeta-induced toxicity. The shortest peptide studied, Abeta(39-42), has been
shown to modulate Abeta oligomerization and inhibit Abeta toxicity. Understanding
the mechanism of these CTFs, especially Abeta(39-42), is of significance for
future therapeutic development of AD and peptidomimetic-based drug development.
Here we used ion mobility spectrometry-mass spectrometry to investigate the
interactions between two modified Abeta(39-42) derivatives, VVIA-NH2 and Ac-VVIA,
and full-length Abeta42. VVIA-NH2 was previously shown to inhibit Abeta toxicity,
whereas Ac-VVIA did not. Our mass spectrometry analysis revealed that VVIA-NH2
binds directly to Abeta42 monomer and small oligomers while Ac-VVIA binds only to
Abeta42 monomer. Ion mobility studies showed that VVIA-NH2 modulates Abeta42
oligomerization by not only inhibiting the dodecamer formation but also
disaggregating preformed Abeta42 dodecamer. Ac-VVIA also inhibits and removes
preformed Abeta42 dodecamer. However, the Abeta42 sample with the addition of Ac
VVIA clogged the nanospray tip easily, indicating that larger aggregates are
formed in the solution in the presence of Ac-VVIA. Molecular dynamics simulations
suggested that VVIA-NH2 binds specifically to the C-terminal region of Abeta42
while Ac-VVIA binds dispersedly to multiple regions of Abeta42. This work implies
that C-terminal interactions and binding to Abeta oligomers are important for C
terminal fragment inhibitors.
PMID- 26439284
TI - Swimming in a crystal.
AB - We study catalytic Janus particles and Escherichia coli bacteria swimming in a
two-dimensional colloidal crystal. The Janus particles orbit individual colloids
and hop between colloids stochastically, with a hopping rate that varies
inversely with fuel (hydrogen peroxide) concentration. At high fuel
concentration, these orbits are stable for 100s of revolutions, and the orbital
speed oscillates periodically as a result of hydrodynamic, and possibly also
phoretic, interactions between the swimmer and the six neighbouring colloids.
Motile E. coli bacteria behave very differently in the same colloidal crystal:
their circular orbits on plain glass are rectified into long, straight runs,
because the bacteria are unable to turn corners inside the crystal.
PMID- 26439286
TI - Characterization of miRNAs from hydrothermal vent shrimp Rimicaris exoculata.
AB - Deep-sea hydrothermal vent shrimp Rimicaris exoculata is a dominant species
aggregating in vent fields along the Mid-Atlantic Ocean Ridge. MicroRNAs play
important roles in life cycles of eukaryotes. However, little is known about
miRNAs of vent animals. In the present study, a small RNA cDNA library from the
muscle of R. exoculata was constructed and the miRNA sequencing was performed.
The results indicated that a total of 7,983,331 raw reads were obtained,
representing 569,354 unique sequences. Based on sequence analysis, R. exoculata
contained 159 conserved miRNAs and 34 novel miRNAs. The conserved miRNAs included
54 families belonging to three different taxonomic units (bilaterian, protostomes
and arthropods). The results also showed that miR-2001, a lost miRNA in
crustaceans, existed in R. exoculata. Among the conserved miRNAs, iso-miRs were
detected. Therefore, this study presented the first insight into the miRNAs of
deep-sea hydrothermal vent animals.
PMID- 26439287
TI - St.Gallen-2015 in Vienna: News from a successful breast cancer conference
transposition!
PMID- 26439285
TI - Reassessment of MxiH subunit orientation and fold within native Shigella T3SS
needles using surface labelling and solid-state NMR.
AB - T3SSs are essential virulence determinants of many Gram-negative bacteria, used
to inject bacterial effectors of virulence into eukaryotic host cells. Their
major extracellular portion, a ~50 nm hollow, needle-like structure, is essential
to host cell sensing and the conduit for effector secretion. It is formed of a
small, conserved subunit arranged as a helical polymer. The structure of the
subunit has been studied by electron cryomicroscopy within native polymers and by
solid-state NMR in recombinant polymers, yielding two incompatible atomic models.
To resolve this controversy, we re-examined the native polymer used for electron
cryomicroscopy via surface labelling and solid-state NMR. Our data show the
orientation and overall fold of the subunit within this polymer is as established
by solid-state NMR for recombinant polymers.
PMID- 26439288
TI - Brownian dynamics simulation of amphiphilic block copolymers with different tail
lengths, comparison with theory and comicelles.
AB - Study on the effect of amphiphilic copolymers structure on their self assembly is
an interesting subject, with important applications in the area of drug delivery
and biological system treatments. Brownian dynamics simulations were performed to
study self-assembly of the linear amphiphilic block copolymers with the same
hydrophilic head, but hydrophobic tails of different lengths. Critical micelle
concentration (CMC), gyration radius distribution, micelle size distribution,
density profiles of micelles, shape anisotropy, and dynamics of micellization
were investigated as a function of tail length. Simulation results were compared
with predictions from theory and simulation for mixed systems of block copolymers
with long and short hydrophobic tail, reported in our previous work.
Interestingly, the equilibrium structural and dynamic parameters of pure and
mixed block copolymers were similarly dependant on the intrinsic/apparent
hydrophobic block length. Log (CMC) was, however; proportional to the tail length
and had a different behavior compared to the mixed system. The power law scaling
relation of equilibrium structural parameters for amphiphilic block copolymers
predicts the same dependence for similar hydrophobic tail lengths, but the power
law prediction of CMC is different, which is due to its simplifying assumptions
as discussed here.
PMID- 26439289
TI - Comparative study on the interfacial electron transfer of zinc porphyrins with
meso-pi-extension at a 2(n) pattern.
AB - Three zinc-tetraarylporphyrins were prepared in order to investigate the effects
of systematic meso-pi-extension on the redox behaviors and interfacial electron
transfer kinetics. The meso-pi-extension increased at a 2(n) pattern, where 2(n)
was the benzene ring number in an aryl group and the aryl group represented
phenyl, naphthyl and pyrenyl group, respectively. The structures of zinc
tetraarylporphyrins and hydroquinone were optimized by using density functional
theory. The bimolecular reactions between zinc-tetraarylporphyrins and
hydroquinone at the liquid-liquid interface were studied by using scanning
electrochemical microscopy. There was an inverse electron transfer rate-overall
driving force dependence by comparison of three bimolecular reactions. It was
suggested that the formation of a precursor between zinc-tetraarylporphyrin
cation and hydroquinone was deeply influenced by the increasing steric hindrance
from phenyl group to pyrenyl group. The electron transfer rate constant depended
strongly on the overall driving force for each bimolecular reaction, with
transfer coefficients of 0.41, 0.37 and 0.39.
PMID- 26439290
TI - Rapid sphere sizing using a Bayesian analysis of reciprocal space imaging data.
AB - Dispersed systems are important in many applications in a wide range of
industries such as the petroleum, pharmaceutical and food industries. Therefore
the ability to control and non-invasively measure the physical properties of
these systems, such as the dispersed phase size distribution, is of significant
interest, in particular for concentrated systems, where microscopy or scattering
techniques may not apply or with very limited output quality. In this paper we
show how reciprocal space data acquired using both 1D magnetic resonance imaging
(MRI) and 2D X-ray micro-tomographic (X-ray MUCT) data can be analysed, using a
Bayesian statistical model, to extract the sphere size distribution (SSD) from
model sphere systems and dispersed food foam samples. Glass spheres-in-xanthan
gels were used as model samples with sphere diameters (D) in the range of
45MUm?D?850MUm. The results show that the SSD was successfully estimated from
both the NMR and X-ray MUCT with a good degree of accuracy for the entire range
of glass spheres in times as short as two seconds. After validating the technique
using model samples, the Bayesian sphere sizing method was successfully applied
to air/water foam samples generated using a microfluidics apparatus with
160MUm?D?400MUm. The effect of different experimental parameters such as the
standard deviation of the bubble size distribution and the volume fraction of the
dispersed phase is discussed.
PMID- 26439291
TI - One of these is not like the others.
AB - A Mycobacterium tuberculosis metA mutant that is auxotrophic for methionine is
unlike other auxotrophic mutants of this important species as methionine
starvation results in rapid death instead of cessation of growth. Evidence
suggests that this phenotype results from starvation affecting essential pathways
that utilize S-adenosylmethionine in addition to methionine.
PMID- 26439292
TI - Biofilm recruitment of Vibrio cholerae by matrix proteolysis.
AB - The appearance of bacterial biofilms involves secretion of polysaccharides and
proteins that form an extracellular matrix embedding the bacteria. Proteases have
also been observed, but their role has remained unclear. Smith and co-workers
have now found that proteolysis can contribute to further recruitment of bacteria
to Vibrio cholerae biofilms.
PMID- 26439294
TI - Roles of indole as an interspecies and interkingdom signaling molecule.
AB - A number of bacteria, and some plants, produce large quantities of indole, which
is widespread in animal intestinal tracts and in the rhizosphere. Indole, as an
interspecies and interkingdom signaling molecule, plays important roles in
bacterial pathogenesis and eukaryotic immunity. Furthermore, indole and its
derivatives are viewed as potential antivirulence compounds against antibiotic
resistant pathogens because of their ability to inhibit quorum sensing and
virulence factor production. Indole modulates oxidative stress, intestinal
inflammation, and hormone secretion in animals, and it controls plant defense
systems and growth. Insects and nematodes can recognize indole, which controls
some of their behavior. This review presents current knowledge regarding indole
and its derivatives, their biotechnological applications and their role in
prokaryotic and eukaryotic systems.
PMID- 26439295
TI - Microbial malaise: how can we classify the microbiome?
AB - The names and lineages of microorganisms are critical to our understanding of the
microbiome. However, microbial taxonomy and phylogeny are in perpetual flux, with
emerging criteria being used to rename and reshape our views of the microbial
world. Different candidate molecular and nonmolecular criteria are often broadly
consistent with one another, which underpins the pluralistic approach to
taxonomy. However, the taxonomic picture is clouded when underlying criteria are
not in agreement, or when reference datasets contain erroneously named organisms.
How does the shifting taxonomic landscape impact our interpretation of microbial
communities, especially in the face of inconsistencies and errors? How can
taxonomy be applied in a consistent way when different users have different
requirements of the classifications that emerge? The key path forward involves
finding ways to integrate conflicting taxonomic criteria, choosing the right
units of analysis for microbiomic studies, and making molecular taxonomy
transparent and accessible in a way that complements current genomic resources.
PMID- 26439293
TI - Bacterial amyloid formation: structural insights into curli biogensis.
AB - Curli are functional amyloid fibers assembled by many Gram-negative bacteria as
part of an extracellular matrix that encapsulates the bacteria within a biofilm.
A multicomponent secretion system ensures the safe transport of the aggregation
prone curli subunits across the periplasm and outer membrane, and coordinates
subunit self-assembly into surface-attached fibers. To avoid the build-up of
potentially toxic intracellular protein aggregates, the timing and location of
the interactions of the different curli proteins are of paramount importance.
Here we review the structural and molecular biology of curli biogenesis, with a
focus on the recent breakthroughs in our understanding of subunit chaperoning and
secretion. The mechanistic insight into the curli assembly pathway will provide
tools for new biotechnological applications and inform the design of targeted
inhibitors of amyloid polymerization and biofilm formation.
PMID- 26439296
TI - Microbial invasions: the process, patterns, and mechanisms.
AB - There has recently been a surge of literature examining microbial invasions into
a variety of environments. These studies often include a component of biological
diversity as a major factor determining an invader's fate, yet common results are
rarely cross-compared. Since many studies only present a snapshot of the entire
invasion process, a bird's eye view is required to piece together the entire
continuum, which we find consists of introduction, establishment, spread, and
impact phases. We further examine the patterns and mechanisms associated with
invasion resistance and create a mechanistic synthesis governed by the species
richness, species evenness, and resource availability of resident communities. We
conclude by exploring the advantages of using a theoretical invasion framework
across different fields.
PMID- 26439297
TI - SAMHD1: at the crossroads of cell proliferation, immune responses, and virus
restriction.
AB - SAMHD1 is a triphosphohydrolase enzyme that controls the intracellular level of
deoxyribonucleoside triphosphates (dNTPs) and plays a role in innate immune
sensing and autoimmune disease. SAMHD1 has also been identified as an intrinsic
virus restriction factor, inactivated through degradation by HIV-2 Vpx or through
a post-transcriptional regulatory mechanism. Phosphorylation of SAMHD1 by cyclin
dependent kinases has been strongly associated with inactivation of the virus
restriction mechanism, providing an association between virus replication and
cell proliferation. Tight regulation of cell proliferation suggests that viruses,
particularly HIV-1 replication, latency, and reactivation, may be similarly
controlled by multiple checkpoint mechanisms that, in turn, regulate dNTP levels.
In this review, we discuss how SAMHD1 is a viral restriction factor, the
mechanism associated with viral restriction, the pathway leading to its
inactivation in proliferating cells, and how strategies aimed at controlling
virus restriction could lead to a functional cure for HIV.
PMID- 26439299
TI - Ten years of maintaining and expanding a microbial genome and metagenome analysis
system.
AB - Launched in March 2005, the Integrated Microbial Genomes (IMG) system is a
comprehensive data management system that supports multidimensional comparative
analysis of genomic data. At the core of the IMG system is a data warehouse that
contains genome and metagenome datasets sequenced at the Joint Genome Institute
or provided by scientific users, as well as public genome datasets available at
the National Center for Biotechnology Information Genbank sequence data archive.
Genomes and metagenome datasets are processed using IMG's microbial genome and
metagenome sequence data processing pipelines and are integrated into the data
warehouse using IMG's data integration toolkits. Microbial genome and metagenome
application specific data marts and user interfaces provide access to different
subsets of IMG's data and analysis toolkits. This review article revisits IMG's
original aims, highlights key milestones reached by the system during the past 10
years, and discusses the main challenges faced by a rapidly expanding system, in
particular the complexity of maintaining such a system in an academic setting
with limited budgets and computing and data management infrastructure.
PMID- 26439298
TI - Stealing the Keys to the Kitchen: Viral Manipulation of the Host Cell Metabolic
Network.
AB - Host cells possess the metabolic assets required for viral infection. Recent
studies indicate that control of the host's metabolic resources is a core host
pathogen interaction. Viruses have evolved mechanisms to usurp the host's
metabolic resources, funneling them towards the production of virion components
as well as the organization of specialized compartments for replication,
maturation, and dissemination. Consequently, hosts have developed a variety of
metabolic countermeasures to sense and resist these viral changes. The complex
interplay between virus and host over metabolic control has only just begun to be
deconvoluted. However, it is clear that virally induced metabolic reprogramming
can substantially impact infectious outcomes, highlighting the promise of
targeting these processes for antiviral therapeutic development.
PMID- 26439300
TI - Rtt107 Is a Multi-functional Scaffold Supporting Replication Progression with
Partner SUMO and Ubiquitin Ligases.
AB - Elucidating the individual and collaborative functions of genome maintenance
factors is critical for understanding how genome duplication is achieved. Here,
we investigate a conserved scaffold in budding yeast, Rtt107, and its three
partners: a SUMO E3 complex, a ubiquitin E3 complex, and Slx4. Biochemical and
genetic findings show that Rtt107 interacts separately with these partners and
contributes to their individual functions, including a role in replisome
sumoylation. We also provide evidence that Rtt107 associates with replisome
components, and both itself and its associated E3s are important for replicating
regions far from initiation sites. Corroborating these results, replication
defects due to Rtt107 loss and genotoxic sensitivities in mutants of Rtt107 and
its associated E3s are rescued by increasing replication initiation events
through mutating two master repressors of late origins, Mrc1 and Mec1. These
findings suggest that Rtt107 functions as a multi-functional platform to support
replication progression with its partner E3 enzymes.
PMID- 26439303
TI - Proteomic analysis of Eimeria acervulina sporozoite proteins interaction with
duodenal epithelial cells by shotgun LC-MS/MS.
AB - Although it has been known for many years that Eimeria acervulina (E. acervulina)
initiates infection by invading the duodenal epithelial cells of chicken, the key
protein molecules and the mechanisms of the parasite in invading are unknow. In
this study, we found that 85 proteins of E. acervulina could bind with the
chicken duodenal epithelial cells from Eimeria protein database. Among them,
sixteen were identified only in Eimeria spp. correlation with invasion and
evasion and 69 proteins were found in Eimeria spp. with more than 2 unique pep
count. Nine out of the 16 proteins and 41 out of the 69 proteins were annotated
according to Gene Ontology Annotation in terms of molecular function, biological
process, and cellular localization. Most of the 9 annotated proteins occurred in
binding, catalytic activity and cellular process whereas, 29 (70.73%) out of the
41 proteins had binding activity and 20 proteins (48.78%) had catalytic activity.
The findings provided an insight into the interactive relationship between E.
acervulina and host cells and will shed new lights on the understanding of
molecular mechanisms of E. acervulina invasion and pathogenesis.
PMID- 26439302
TI - The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated
Methylation of H3K79.
AB - AF10, a DOT1L cofactor, is required for H3K79 methylation and cooperates with
DOT1L in leukemogenesis. However, the molecular mechanism by which AF10 regulates
DOT1L-mediated H3K79 methylation is not clear. Here we report that AF10 contains
a "reader" domain that couples unmodified H3K27 recognition to H3K79 methylation.
An AF10 region consisting of a PHD finger-Zn knuckle-PHD finger (PZP) folds into
a single module that recognizes amino acids 22-27 of H3, and this interaction is
abrogated by H3K27 modification. Structural studies reveal that H3 binding
triggers rearrangement of the PZP module to form an H3(22-27)-accommodating
channel and that the unmodified H3K27 side chain is encased in a compact hydrogen
bond acceptor-lined cage. In cells, PZP recognition of H3 is required for H3K79
dimethylation, expression of DOT1L-target genes, and proliferation of DOT1L
addicted leukemic cells. Together, our results uncover a pivotal role for H3K27
via readout by the AF10 PZP domain-in regulating the cancer-associated enzyme
DOT1L.
PMID- 26439304
TI - Independent amino acid residues in the S2 pocket of falcipain-3 determine its
specificity for P2 residues in substrates.
AB - Falcipain-3 (FP3) is an essential and drug target cysteine protease of the most
lethal human malaria parasite Plasmodium falciparum. FP3 and its majority of
homologs in malaria parasites prefer Leu at the P2 position in substrates and
inhibitors, whereas its major host homolog cathepsin L prefers Phe. However, FP3
is much less active on peptide substrates and has negligible activity against a
P2 Arg-containing substrate (Z-RR-AMC) compared to its paralog falcipain-2A
(FP2A). To identify the specificity determinants, the S2/3 pocket residues of FP3
were substituted with the corresponding residues in FP2 or cathepsin L, and the
wild type and mutant proteases were assessed for hydrolysis of peptide and
protein substrates. Our results indicate that the S2 pocket residues I94 and P181
of FP3 are chiefly responsible for its P2 Leu preference and negligible activity
for Z-RR-AMC, respectively. E243 in FP3 and the corresponding residue D234 in FP2
have a key role in Z-RR-AMC hydrolysing activity, possibly through stabilization
of side chain interactions, as their substitution with Ala abolished the
activity. Several FP3 mutants, which retained P2 Leu preference and showed
similar or more activity than wild type FP3 on peptide substrates, degraded
haemoglobin less efficiently than wild type FP3, suggesting that multiple
residues contribute to haemoglobinase activity. Furthermore, P181 and E243 appear
to contribute to the optimum activity of FP3 in the food vacuole milieu (~pH
5.5). The identification of residues determining specificity of FP3 could aid in
developing specific inhibitors of FP3 and its homologs in malaria parasites.
PMID- 26439301
TI - YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic
Enhancers.
AB - The Hippo/YAP signaling pathway is a crucial regulator of tissue growth, stem
cell activity, and tumorigenesis. However, the mechanism by which YAP controls
transcription remains to be fully elucidated. Here, we utilize global chromatin
occupancy analyses to demonstrate that robust YAP binding is restricted to a
relatively small number of distal regulatory elements in the genome. YAP
occupancy defines a subset of enhancers and superenhancers with the highest
transcriptional outputs. YAP modulates transcription from these elements
predominantly by regulating promoter-proximal polymerase II (Pol II) pause
release. Mechanistically, YAP interacts and recruits the Mediator complex to
enhancers, allowing the recruitment of the CDK9 elongating kinase. Genetic and
chemical perturbation experiments demonstrate the requirement for Mediator and
CDK9 in YAP-driven phenotypes of overgrowth and tumorigenesis. Our results here
uncover the molecular mechanisms employed by YAP to exert its growth and
oncogenic functions, and suggest strategies for intervention.
PMID- 26439306
TI - All-Printed, Foldable Organic Thin-Film Transistors on Glassine Paper.
AB - All-printed, foldable organic thin-film transistors are demonstrated on glassine
paper with a combination of advanced materials and processing techniques.
Glassine paper provides a suitable surface for high-performance printing methods,
while graphene electrodes and an ion-gel gate dielectric enable robust stability
over 100 folding cycles. Altogether, this study features a practical platform for
low-cost, large-area, and foldable electronics.
PMID- 26439305
TI - P-Selectin Sustains Extramedullary Hematopoiesis in the Gata1 low Model of
Myelofibrosis.
AB - Splenomegaly is a major manifestation of primary myelofibrosis (PMF) contributing
to clinical symptoms and hematologic abnormalities. The spleen from PMF patients
contains increased numbers of hematopoietic stem cells (HSC) and megakaryocytes
(MK). These MK express high levels of P-selectin (P-sel) that, by triggering
neutrophil emperipolesis, may cause TGF-beta release and disease progression.
This hypothesis was tested by deleting the P-sel gene in the myelofibrosis mouse
model carrying the hypomorphic Gata1(low) mutation that induces megakaryocyte
abnormalities that recapitulate those observed in PMF. P-sel(null) Gata1(low)
mice survived splenectomy and lived 3 months longer than P-sel(WT) Gata1(low)
littermates and expressed limited fibrosis and osteosclerosis in the marrow or
splenomegaly. Furthermore, deletion of P-sel disrupted megakaryocyte/neutrophil
interactions in spleen, reduced TGF-beta content, and corrected the HSC
distribution that in Gata1(low) mice, as in PMF patients, is abnormally expanded
in spleen. Conversely, pharmacological inhibition of TGF-beta reduced P-sel
expression in MK and corrected HSC distribution. Spleens, but not marrow, of
Gata1(low) mice contained numerous cKIT(pos) activated fibrocytes, probably of
dendritic cell origin, whose membrane protrusions interacted with MK establishing
niches hosting immature cKIT(pos) hematopoietic cells. These activated fibrocytes
were not detected in spleens from P-sel(null) Gata1(low) or TGF-beta-inhibited
Gata1(low) littermates and were observed in spleen, but not in marrow, from PMF
patients. Therefore, in Gata1(low) mice, and possibly in PMF, abnormal P-sel
expression in MK may mediate the pathological cell interactions that increase TGF
beta content in MK and favor establishment of a microenvironment that supports
myelofibrosis-related HSC in spleen.
PMID- 26439307
TI - Lichenoid drug eruption induced by colchicine.
PMID- 26439308
TI - Paritaprevir/ritonavir, ombitasvir, and dasabuvir for treatment of recurrent
hepatitis C virus infection in the human immunodeficiency virus coinfected liver
transplant recipient.
PMID- 26439310
TI - Determining the arsenic, cadmium, lead, copper and chromium contents by atomic
absorption spectrometry in Pangasius fillets from Vietnam.
AB - BACKGROUND: Pangasius is a fish produced on a large scale in Vietnam and exported
to many countries. Since river contamination from human activities can affect the
safety of this food, fish consumption can cause exposure to potentially toxic
elements for humans. The aim of this study, therefore, was to assess arsenic,
cadmium, lead, copper and chromium contents by atomic absorption spectrometry in
Pangasius fillet produced in the provinces of Dong Thap and Can Tho (Vietnam) and
exported to Brazil. RESULTS: The limits of detection were: arsenic 0.5443 ug kg(
1) , cadmium 0.0040 mg kg(-1) , chromium 0.0004 mg kg(-1) , copper 0.0037 mg kg(
1) and lead 0.0284 mg kg(-1) . Analysis of 20 samples showed results below the
limit of detection for arsenic, chromium and lead, while copper average
concentration was 0.0234 mg kg(-1) . Cadmium average concentration was 0.0547 mg
kg(-1) , with no significant difference between the two regions studied.
CONCLUSION: The samples of Pangasius had no detectable concentrations of arsenic,
chromium, copper and lead, and do not represent a hazard to public health.
However, cadmium analysis revealed non-compliant samples, demonstrating the
importance of monitoring the quality of imported Pangasius fish. (c) 2015 Society
of Chemical Industry.
PMID- 26439311
TI - From species distributions to meta-communities.
AB - The extent that biotic interactions and dispersal influence species ranges and
diversity patterns across scales remains an open question. Answering this
question requires framing an analysis on the frontier between species
distribution modelling (SDM), which ignores biotic interactions and dispersal
limitation, and community ecology, which provides specific predictions on
community and meta-community structure and resulting diversity patterns such as
species richness and functional diversity. Using both empirical and simulated
datasets, we tested whether predicted occurrences from fine-resolution SDMs
provide good estimates of community structure and diversity patterns at
resolutions ranging from a resolution typical of studies within reserves (250 m)
to that typical of a regional biodiversity study (5 km). For both datasets, we
show that the imprint of biotic interactions and dispersal limitation quickly
vanishes when spatial resolution is reduced, which demonstrates the value of SDMs
for tracking the imprint of community assembly processes across scales.
PMID- 26439309
TI - Comparative analysis of mediastinal fat-associated lymphoid cluster development
and lung cellular infiltration in murine autoimmune disease models and the
corresponding normal control strains.
AB - We previously discovered mediastinal fat-associated lymphoid clusters (MFALCs) as
novel lymphoid clusters associated with mediastinal fat tissue in healthy mice.
However, no data about their morphology in immune-associated disease conditions,
and their relationship with lung infiltration, is available to date. In the
present study, we compared the morphological features of MFALCs in 4-month-old
male murine autoimmune disease models (MRL/MpJ-lpr mice and BXSB/MpJ-Yaa mice)
with those of the corresponding control strains (MRL/MpJ and BXSB/MpJ,
respectively). In addition, we analysed their correlation with lung infiltration.
Furthermore, immunohistochemistry for CD3, B220, Iba1, Gr1 and BrdU was performed
to detect T cells and B cells, macrophages, granulocytes and proliferating cells,
respectively. The spleen weight to body weight ratios and anti-double-stranded
DNA autoantibody titres were found to be significantly higher in the autoimmune
models than in the control strains. Furthermore, the autoimmune model presented
prominent MFALCs, with a significantly greater ratio of lymphoid cluster area to
total mediastinal fat tissue area, and more apparent diffused cellular
infiltration into the lung lobes than the other studied strains. Higher numbers
of T and B cells, macrophages and proliferating cells, but fewer granulocytes,
were observed in the autoimmune models than in the control strains.
Interestingly, a significant positive Pearson's correlation between the size of
the MFALCs and the density of CD3-, B220- and Iba1-positive cells in the lung was
observed. Therefore, our data suggest a potentially important role for MFALCs in
the progression of lung disease. However, further investigation is required to
clarify the pathological role of MFALCs in lung disease, especially in
inflammatory disorders.
PMID- 26439312
TI - The transition from naive to primed nociceptive state: A novel wind-up protocol
in mice.
AB - Wind-up (WU) is a progressive, frequency-dependent facilitation of spinal cord
neurons in response to repetitive nociceptive stimulation of constant intensity.
We identified a new WU-associated phenomenon in naive mice (not exposed to
noxious stimulation immediately prior to WU stimulation), which were subjected to
a novel experimental protocol composed of three consecutive trains of WU
stimulation. The 1st train produced a typical linear 'wind-up' curve as expected
following a repeating series of stimuli; in addition, this 1st train sensitized
('primed') the nociceptive system so that the responses to two subsequent trains
(inter-train interval of 10 min) were significantly amplified compared with the
response to the 1st train. We named this augmented response potentiation-of
windup, or "PoW". The PoW phenomenon appears to be centrally mediated, as the
augmented response was suppressed by administration of an NMDA receptor
antagonist (MK-801) and by cutting the spinal cord. Furthermore, the PoW protocol
is accompanied by enhanced pain behavior. The 'priming' effect of the 1st train
could be mimicked by exposure to natural noxious stimuli prior to the PoW
protocol. Presumably, the PoW phenomenon has not been previously reported due to
a procedural reason: typically, WU protocols have been executed in 'primed'
rather than naive animals, i.e., animals exposed to nociceptive stimulation prior
to the actual WU recording. Our findings indicate that the PoW paradigm can
distinguish between 'naive' and 'primed' states, suggesting its use as a tool for
the assessment of central sensitization.
PMID- 26439314
TI - Accordion-like swelling of layered perovskite crystals via massive permeation of
aqueous solutions into 2D oxide galleries.
AB - Platelet crystals of a layered perovskite showed massive accordion-like swelling
in a tetrabutylammonium hydroxide solution. The permeation of the solution
induced the huge expansion of the interlayer spacing as well as the crystal
thickness up to 50-fold, leading to a very high water content of >90 wt%.
PMID- 26439315
TI - A Unique Case of JOAG With Lamellar Ichthyosis With Rickets: A Case Report and
Review of the Literature.
AB - PURPOSE: Ichthyosis is known to have ocular associations such as blepharitis,
hypertrophic conjunctivitis, corneal vascularization, ectropion, lagophthalmos,
etc. However, no reports of its association with glaucoma are there, to the best
of our knowledge. We report a unique case of juvenile open-angle glaucoma (JOAG)
with lamellar ichthyosis. METHOD: A 16-year-old male child presented with a
gradual, painless progressive diminution of vision in both eyes over a period of
3 years. Systemic examination revealed stunted body growth with knock-knees,
suggestive of late-onset rickets. Generalized dry scaly lesions with erythema,
along with hyperkeratosis of the palms and the soles, suggestive of lamellar
ichthyosis were present. On ocular examination, the intraocular pressure was 36
mm Hg; optic nerve head examination revealed a horizontally oval disc with near
total cupping in the right eye and total cupping in the left eye, with extensive
neuroretinal rim thinning and pallor. Gonioscopy showed wide open angles with
prominent iris processes. Screening of JOAG-associated genes (MYOC, NTF4, WDR36,
and CYP1B1) and ichthyosis-associated gene (TGM1) was performed by the direct PCR
sequencing method. RESULTS: A diagnosis of JOAG with advanced glaucomatous optic
neuropathy with lamellar ichthyosis and rickets was made. The patient underwent
right followed by left eye trabeculectomy with 0.2 mg/dL MMC (for 1 min).
Postoperatively, the intraocular pressure was 8 mm Hg at 1 week, and 12 to 14 mm
Hg at the 6-week, the 3-month, and the 6-month follow-up, and the visual acuity
was maintained in the right eye. No mutations in MYOC, NTF4, WDR36, CYP1B1, and
TGM1 were observed in the patient and his family. CONCLUSIONS: An association of
glaucoma with ichthyosis should be kept in mind. Therefore, a detailed baseline
ocular examination in children with ichthyosis is required, as early detection of
glaucoma could prevent irreversible blindness.
PMID- 26439316
TI - Answer to the authors.
PMID- 26439313
TI - Ziram, a pesticide associated with increased risk for Parkinson's disease,
differentially affects the presynaptic function of aminergic and glutamatergic
nerve terminals at the Drosophila neuromuscular junction.
AB - Multiple populations of aminergic neurons are affected in Parkinson's disease
(PD), with serotonergic and noradrenergic loci responsible for some non-motor
symptoms. Environmental toxins, such as the dithiocarbamate fungicide ziram,
significantly increase the risk of developing PD and the attendant spectrum of
both motor and non-motor symptoms. The mechanisms by which ziram and other
environmental toxins increase the risk of PD, and the potential effects of these
toxins on aminergic neurons, remain unclear. To determine the relative effects of
ziram on the synaptic function of aminergic versus non-aminergic neurons, we used
live-imaging at the Drosophila melanogaster larval neuromuscular junction (NMJ).
In contrast to nearly all other studies of this model synapse, we imaged
presynaptic function at both glutamatergic Type Ib and aminergic Type II boutons,
the latter responsible for storage and release of octopamine, the invertebrate
equivalent of noradrenalin. To quantify the kinetics of exo- and endo-cytosis, we
employed an acid-sensitive form of GFP fused to the Drosophila vesicular
monoamine transporter (DVMAT-pHluorin). Additional genetic probes were used to
visualize intracellular calcium flux (GCaMP) and voltage changes (ArcLight). We
find that at glutamatergic Type Ib terminals, exposure to ziram increases
exocytosis and inhibits endocytosis. By contrast, at octopaminergic Type II
terminals, ziram has no detectable effect on exocytosis and dramatically inhibits
endocytosis. In contrast to other reports on the neuronal effects of ziram, these
effects do not appear to result from perturbation of the Ubiquitin Proteasome
System (UPS) or calcium homeostasis. Unexpectedly, ziram also caused spontaneous
and synchronized bursts of calcium influx (measured by GCaMP) and electrical
activity (measured by ArcLight) at aminergic Type II, but not glutamatergic Type
Ib, nerve terminals. These events are sensitive to both tetrodotoxin and cadmium
chloride, and thus appear to represent spontaneous depolarizations followed by
calcium influx into Type II terminals. We speculate that the differential effects
of ziram on Type II versus Type Ib terminals may be relevant to the specific
sensitivity of aminergic neurons in PD, and suggest that changes in neuronal
excitability could contribute to the increased risk for PD caused by exposure to
ziram. We also suggest that the fly NMJ will be useful to explore the synaptic
effects of other pesticides associated with an increased risk of PD.
PMID- 26439317
TI - To editor, orthodontics and craniofacial research.
PMID- 26439318
TI - Metabolic engineering of a laboratory-evolved Thermobifida fusca muC strain for
malic acid production on cellulose and minimal treated lignocellulosic biomass.
AB - Malic acid is mainly used as an acidulant and taste enhancer in the beverage and
food industry. Previously, a mutant strain Thermobifida fusca muC, obtained by
adaptive evolution was found to accumulate malic acid on cellulose with low
yield. In this study, the malic acid synthesis pathway in T. fusca muC was
confirmed to be from phosphoenolpyruvate to oxaloacetate, followed by reduction
of oxaloacetate to malate. To increase the yield of malic acid by the muC strain
significantly, the carbon flux from pyruvate was redirected to oxaloacetate by
expressing an exogenous pyruvate carboxylase (PCx) gene from Corynebacterium
glutamicum ATCC 13032 in the chromosome of T. fusca muC-16. The yield of malic
acid in the engineered strain muC-16 was increased by 47.9% compared to the
parent strain muC. The muC-16 strain was then grown on ~100 g/L cellulose and the
highest titer of malic acid was 62.76 g/L by batch fermentation. T. fusca muC-16
strain converted milled corn stover to malic acid with the highest titer of 21.47
g/L with minimal treatment.
PMID- 26439320
TI - Anxiety and depression in long-term testicular germ cell tumor survivors.
AB - OBJECTIVE: Despite a good prognosis, the typically young age at diagnosis and
physical sequelae may cause psychological distress in germ cell tumor survivors.
We aimed to determine the frequency of anxiety and depression and analyze the
impact of demographic and disease-related factors. METHOD: We enrolled N=164
testicular germ cell tumor survivors receiving routine follow-up care at the
University Cancer Center Hamburg and a specialized private practice (mean, 11.6
years after diagnosis). Patients completed the Generalized Anxiety Disorder
Screener-7, the Patient Health Questionnaire-9 and the Memorial Symptom
Assessment Scale-Short Form. RESULTS: We found clinically significant anxiety
present in 6.1% and depression present in 7.9% of survivors. A higher number of
physical symptoms and having children were significantly associated with higher
levels of both anxiety and depression in multivariate regression analyses
controlling for age at diagnosis, cohabitation, socioeconomic status, time since
diagnosis, metastatic disease and relapse. Younger age at diagnosis and shorter
time since diagnosis were significantly associated with higher anxiety.
CONCLUSION: Although rates of clinically relevant anxiety and depression were
comparably low, attention toward persisting physical symptoms and psychosocial
needs related to a young age at diagnosis and having children will contribute to
address potential long-term psychological distress in germ cell tumor survivors.
PMID- 26439321
TI - Gouty arthropathy: Review of clinico-pathologic and imaging features.
AB - Gout is a common inflammatory arthropathy in adults, with the prevalence
increasing in males of older age. It occurs when monosodium urate (MSU) crystals
are deposited in joints and connective tissue causing inflammation. The gold
standard for the diagnosis of gout is the demonstration of negatively
birefringent, needle-shaped MSU crystals through synovial fluid aspiration.
However, this is an invasive technique and may not always be conclusive or
feasible. Imaging techniques have been developed to aid in diagnosis of gout non
invasively. Radiography has a low utility in the early diagnosis of gout and
demonstrates erosions in late stages. Ultrasound (US) has a high overall
sensitivity in diagnosing gout with the 'double contour' sign having a high
specificity. Magnetic resonance imaging is good at detecting tophi, bone marrow
oedema and erosions, but has a limited role in diagnosis because of its high cost
and limited availability. Conventional computed tomography (CT) has no role in
the routine diagnosis of gout before development of erosions and tophi. A newer
technology, dual-energy CT (DECT) has been shown to be able to detect MSU
crystals burden with high accuracy. It has a higher specificity and lower
sensitivity that US in gout diagnosis. However, because of radiation exposure and
cost, it has a better utility in diagnosing clinically suspected gout complicated
by other concurrent rheumatologic conditions or if radiography, US and synovial
aspiration are inconclusive or not feasible. This paper will review the clinico
pathologic and imaging features of gouty arthropathy.
PMID- 26439319
TI - Epidemiological, clinical, virological features of hepatitis B newly diagnosed in
2011 in Marseille University hospitals, southeastern France.
AB - Hepatitis B virus (HBV) infection is a public health problem. In France, 0.68% of
adults are chronically infected. We aimed to describe the epidemiological,
virological and clinical characteristics of HBV infections newly diagnosed in
2011 in University hospitals of Marseille, the second largest French city. HBV
serology was performed for 18,130 sera from 15,744 patients. A total of 167
patients were newly-diagnosed with HBV based upon the detection of hepatitis B
surface antigen and anti-hepatitis B core antibodies. Clinico-epidemiological
features were analyzed for 78 patients. Patients included a majority of men
(59%), women being significantly younger with a mean age of 36 +/- 17 versus 43.5
+/- 16.2 years (P = 0.009). Country of birth was available for 52 patients and
35% of them originated from sub-Saharan Africa. Levels of the liver biological
parameters were significantly lower in women compared to men, in whom mean
alanine aminotransferase and gammaglutamyl transferase levels were 24 +/- 39
versus 37 +/- 36 IU/l (P = 0.0001) and 20 +/- 20 versus 51 +/- 53 IU/l (P =
0.0001), respectively. Co-infections with hepatitis C and human immunodeficiency
viruses were found in 5% and 6% of the patients, respectively. HBV DNA was
detectable in 90% of the HBeAg-negative patients. In addition, there was a
positive correlation between the HBsAg titer and the HBV DNA level (P = 0.001).
Genotype D was the most common HBV genotype and was found in 53% of the patients
tested, followed by genotype E (21%). HBV remains a major concern with a slightly
greater number of new diagnoses than in 2004. HBV genetic diversity was
substantial in the present cohort.
PMID- 26439322
TI - Catalytic Asymmetric Michael Reaction of 5H-Oxazol-4-Ones with alpha,beta
Unsaturated Acyl Imidazoles.
AB - The asymmetric Michael reaction between 5H-oxazol-4-ones and alpha,beta
unsaturated acyl imidazoles is reported. A novel 2-benzo[b]thiophenyl-modified
chiral ProPhenol species is synthesized and used as a ligand, leading to good
enantioselectivities in this asymmetric conjugate addition reaction. Furthermore,
the introduction of phenol additives as achiral co-ligands is found to improve
the reaction's chemical yields, diastereoselectivities, and enantioselectivities.
PMID- 26439323
TI - Measurement of Anti-Factor Xa Activity in Patients on Apixaban for Non-Valvular
Atrial Fibrillation.
AB - BACKGROUND: Chromogenic anti-factor Xa activity (AXA) assay is reported to be the
most appropriate method to measure the pharmacodynamics of apixaban, but the
distribution of AXA in non-valvular atrial fibrillation (NVAF) patients on
apixaban therapy has not been fully elucidated. METHODS AND RESULTS: Steady-state
trough and peak AXA were measured in 124 NVAF patients taking apixaban. In 25
patients, baseline, first peak, and trough AXA were also examined, and were
0.01+/-0.02 IU/ml, 0.83+/-0.43 IU/ml, and 0.34+/-0.17 IU/ml, respectively. First
trough AXA was significantly lower than steady-state trough AXA, although it was
significantly higher than baseline (P<0.0001). Similarly, first peak AXA was
significantly lower than steady-state peak AXA (P<0.0001). In 124 patients,
steady-state peak AXA was significantly higher in the 5-mg b.i.d. group than in
the 2.5-mg b.i.d. group (2.05+/-0.73 IU/ml vs. 1.51+/-0.65 IU/ml, respectively;
P<0.001), although there was no significant difference in trough AXA. Other than
dose, age and serum creatinine were significantly related to both trough and peak
AXA. CONCLUSIONS: The distribution of AXA in Japanese NVAF patients on apixaban
therapy in daily clinical practice both in the acute and steady-state phase was
measured. In patients taking apixaban, measurement of AXA clearly showed the
pharmacodynamic profile of this drug.
PMID- 26439324
TI - Carotid Intima-Media Thickness in Patients With a History of Kawasaki Disease.
AB - BACKGROUND: Kawasaki disease (KD) is an acute pediatric vasculitis with coronary
artery aneurysms (CAA) as its main complication. Concerns have been raised
regarding the possibility of a predisposition of KD to premature cardiovascular
disease (CVD) risk later in life. Our aim was to assess carotid intima-media
thickness (cIMT), as a surrogate marker of CVD risk, in patients with a history
of KD compared with unaffected controls. METHODS AND RESULTS: B-mode ultrasound
cIMT measurements were performed in 168 patients with a history of KD, and 82
controls; 7 patients were excluded because of incomplete cIMT assessments. Mean
cIMT (+/-SD) was increased in patients with KD compared with controls (0.378+/
0.030 mm vs. 0.360+/-0.027 mm, respectively; P adjusted <0.0001). If the cIMTs of
CAA-negative patients and controls were plotted against age, increased cIMT was
only apparent at young age. In patients with CAA, increased cIMT was observed
over the entire age range. CONCLUSIONS: Our findings show that arterial wall
thickening is more apparent in patients with a history of KD as compared with
controls. In CAA-negative patients, cIMT is indistinguishable from controls at
older age, whereas an increased cIMT is observed at any age in patients with CAA,
suggesting a more general and severe effect of KD on the arterial wall.
PMID- 26439326
TI - A meta-analysis of adjusted observational studies and randomized controlled
trials of endovascular versus open surgical repair for ruptured abdominal aortic
aneurysm.
AB - INTRODUCTION: The aim of the present meta-analysis was to determine whether
endovascular aneurysm repair (EVAR) reduces perioperative mortality and improves
overall survival compared with open surgical repair (OSR) in patients with
ruptured abdominal aortic aneurysm (RAAA). EVIDENCE ACQUISITION: Eligible studies
were observational studies with adjusted risk estimates or randomized controlled
trials (RCTs) of EVAR versus OSR enrolling individuals with RAAA and reporting
perioperative (30-day or in-hospital) or overall (>=3-month) all-cause mortality.
EVIDENCE SYNTHESIS: Twenty-four adjusted observational studies and 4 RCTs
enrolling a total of 56,826 patients with RAAA were identified and included. For
perioperative all-cause mortality, pooled analyses of 22 adjusted observational
studies and 4 RCTs respectively demonstrated a statistically significant 49%
reduction with EVAR relative to OSR (odds ratio [OR]=0.51; 95% confidence
interval [CI]: 0.44 to 0.59; P<0.00001) and no statistically significant
difference between EVAR and OSR (OR=0.91; 95% CI: 0.68 to 1.22; P=0.53) (P for
subgroup differences = 0.0006). For overall (3 months to 8 years) all-cause
mortality, a pooled analysis of 7 adjusted observational studies (hazard ratio
[HR]=0.92; 95% CI: 0.77 to 1.10; P=0.37) and 3 RCTs (HR=0.89; 95% CI: 0.69 to
1.14; P=0.34) demonstrated no statistically significant difference between EVAR
and OSR (P for subgroup differences = 0.81). CONCLUSIONS: In patients with RAAA,
EVAR is likely effective in prevention of perioperative overall (3 months to 8
years), not all-cause mortality.
PMID- 26439327
TI - Hypomethylation and hypohydroxymethylation of DNA in hepatocellular carcinoma and
cholangiocarcinoma.
PMID- 26439325
TI - Patient-reported physical functioning predicts the success of hematopoietic cell
transplantation (BMT CTN 0902).
AB - BACKGROUND: In hematopoietic cell transplantation (HCT), current risk adjustment
strategies are based on clinical and disease-related variables. Although patient
reported outcomes (PROs) predict mortality in multiple cancers, they have been
less well studied within HCT. Improvements in risk adjustment strategies in HCT
would inform patient selection, patient counseling, and quality reporting. The
objective of the current study was to determine whether pre-HCT PROs, in
particular physical health, predict survival among patients undergoing autologous
or allogeneic transplantation. METHODS: In this secondary analysis, the authors
studied pre-HCT PROs that were reported by 336 allogeneic and 310 autologous HCT
recipients enrolled in the Blood and Marrow Transplant Clinical Trials Network
(BMT CTN) 0902 protocol, a study with broad representation of patients who
underwent transplantation in the United States. RESULTS: Among allogeneic HCT
recipients, the pre-HCT Medical Outcomes Study Short Form-36 Health Survey (SF
36) physical component summary (PCS) scale independently predicted overall
mortality (hazards ratio, 1.40 per 10-point decrease; P<.001) and performed at
least as well as currently used, non-PRO risk indices. Survival probability
estimates at 1 year for the first, second, third, and fourth quartiles of the
baseline PCS were 50%, 65%, 75%, and 83%, respectively. Early post-HCT decreases
in PCS were associated with higher overall and treatment-related mortality. When
adjusted for patient variables included in the US Stem Cell Therapeutic Outcomes
Database model for transplant center-specific reporting, the SF-36 PCS retained
independent prognostic value. CONCLUSIONS: PROs have the potential to improve
prognostication in HCT. The authors recommend the routine collection of PROs
before HCT, and consideration of the incorporation of PROs into risk adjustment
for quality reporting.
PMID- 26439328
TI - Combined Effects of Sedentary Behavior and Moderate-to-Vigorous Physical Activity
on Cardiovascular Health in Older, Community-Dwelling Latinos.
AB - This study examined the combined effects of sedentary behavior and moderate-to
vigorous physical activity (MVPA) on cardiovascular health in older Latinos. In a
cross-sectional sample of 147 older, community-dwelling Latinos, time spent in
sedentary behavior and MVPA were obtained using accelerometers. Analyses examined
the effects of a measure of physical activity that combined levels of sedentary
behavior (+/- 10 daily hours) and MVPA (< 30, 30-150, or > 150 weekly minutes) on
cardiovascular health outcomes (blood pressure, BMI, waist circumference,
cardiorespiratory fitness). Results suggest that cardiovascular health benefits
of MVPA on BMI (p = .005), waist circumference (p = .002), and cardiorespiratory
fitness (p = .012) may depend on a participant's level of sedentary behavior. For
all three, health benefits of 30-150 weekly minutes of MVPA were found only for
those without excessive sedentary behavior (>= 10 hr). Sedentary behavior may
negatively impact cardiovascular health despite moderate participation in MVPA.
Health guidelines should suggest reducing sedentary behavior while increasing
MVPA.
PMID- 26439330
TI - Equilibrium Shape of Colloidal Crystals.
AB - Assembling colloidal particles into highly ordered configurations, such as
photonic crystals, has significant potential for enabling a broad range of new
technologies. Facilitating the nucleation of colloidal crystals and developing
successful crystal growth strategies require a fundamental understanding of the
equilibrium structure and morphology of small colloidal assemblies. Here, we
report the results of a novel computational approach to determine the equilibrium
shape of assemblies of colloidal particles that interact via an experimentally
validated pair potential. While the well-known Wulff construction can accurately
capture the equilibrium shape of large colloidal assemblies, containing O(10(4))
or more particles, determining the equilibrium shape of small colloidal
assemblies of O(10) particles requires a generalized Wulff construction technique
which we have developed for a proper description of equilibrium structure and
morphology of small crystals. We identify and characterize fully several "magic"
clusters which are significantly more stable than other similarly sized clusters.
PMID- 26439329
TI - The value of short- and long-acting glucagon-like peptide-1 agonists in the
management of type 2 diabetes mellitus: experience with exenatide.
AB - BACKGROUND: Only about half of patients with type 2 diabetes treated with
antihyperglycemic drugs achieve glycemic control (HbA1c <7%), most commonly due
to poor treatment adherence. Glucagon-like peptide-1 (GLP-1) receptor agonists
act on multiple targets involved in glucose homeostasis and have a low risk of
causing hypoglycemia. While GLP-1 receptor (GLP-1R) agonists share the same
mechanism of action, clinical profiles of individual agents differ, particularly
between short- and long-acting agents. In this article, recent findings regarding
the pharmacology of GLP-1 agonists are reviewed, and the clinical effects of
short- versus long-acting agents are compared. DATA SOURCES: Relevant articles
were identified through a search of PubMed using the keywords glucagon-like
peptide-1, GLP-1, glucagon-like peptide-1 receptor agonist, GLP-1R agonist, and
exenatide for publications up to 22 May 2015. Supporting data were obtained from
additional searches for albiglutide, dulaglutide, liraglutide and lixisenatide as
well as from the bibliographies of key articles. FINDINGS: Short-acting GLP-1R
agonists produce greater reductions in postprandial glucose levels by slowing
gastric emptying, whereas long-acting GLP-1R agonists produce greater reductions
in fasting blood glucose by stimulating insulin secretion from the pancreas.
These characteristics can be exploited to provide individualized treatment to
patients. A large body of evidence supports the benefits of short- and long
acting exenatide as add-on therapy in patients with inadequate glycemic control
despite maximum tolerated doses of metformin and/or sulfonylurea. Exenatide is
generally well tolerated and no new safety concerns were identified during long
term follow-up of up to 5 years. A limitation of this review of short-and long
acting GLP-1 receptor agonists is that it focuses on exenatide rather than all
the drugs in this class. However, the focus on a single molecule helps to avoid
any confusion that may be introduced as a result of differences in molecular
structure and size. CONCLUSIONS: Short-acting GLP-1R agonists including exenatide
are well suited to patients with type 2 diabetes with exaggerated postprandial
glucose excursions and for co-administration with basal insulin therapy. Long
acting GLP-1R agonists including once weekly exenatide offer greater convenience
and are well suited to patients who require specific control of fasting
hyperglycemia.
PMID- 26439331
TI - Zoomusicology.
PMID- 26439332
TI - Vectored antibody gene delivery mediates long-term contraception.
AB - Development of non-surgical methods of long-term or permanent contraception
remains a challenge. Towards this objective, we show that intramuscular injection
of a replication-incompetent, recombinant adeno-associated virus (rAAV) designed
to express an antibody that binds gonadotropin-releasing hormone (GnRH), a master
regulator of reproduction in vertebrates, results in long-term infertility in
male and female mice. Female mice are also rendered infertile through rAAV
dependent expression of an antibody that binds to the zona pellucida (ZP), a
glycoprotein matrix that surrounds the egg and functions as a sperm-binding site.
Many proteins known or suspected to be important for reproduction can be
targeted, potentially reversibly, using this approach, which we refer to as
vectored contraception (VC).
PMID- 26439333
TI - Eurasian reed warblers compensate for virtual magnetic displacement.
PMID- 26439334
TI - Long-term census data reveal abundant wildlife populations at Chernobyl.
PMID- 26439335
TI - Spatial Cognition: Grid Cell Firing Depends on Self-Motion Cues.
AB - A recent study has found that the periodic spatial activity of grid cells is
completely degraded when animals are moved passively around an enclosure,
strengthening the view that grid-firing is generated on the basis of self-motion
information.
PMID- 26439336
TI - Animal Memory: Chimpanzees Anticipate What Comes Next in Short Movies.
AB - A recent study shows that chimpanzees remember a movie they viewed one day
earlier, and their eye movements show that they anticipate certain actions in
that movie before those actions occur by looking to parts of the scene that are
about to become relevant to the storyline.
PMID- 26439337
TI - Visual Neuroscience: Dissociating Perceptual and Occulomotor Localization of
Moving Objects.
AB - A new experiment shows that the perceived motion path of a textured object is
affected both by the path of the object and by the motion of texture within it,
but that eye movements attempting to intercept the object are unaffected by the
texture movement.
PMID- 26439339
TI - Animal Navigation: Birds Have Magnetic Maps.
AB - New 'virtual displacement' experiments demonstrate that migrating reed warblers
know the magnetic coordinates of their destination, and can set a novel course to
their goal with only magnetic-field parameters as a guide.
PMID- 26439338
TI - Sensory Biology: Novel Peripheral Organization for Better Smell.
AB - Sensory systems have adopted various ways to enhance detection and
discrimination. A recent study shows a novel spatial organization of sensory
cells in the peripheral olfactory system in mice for better odor detection.
PMID- 26439340
TI - Stomatal Patterning: SERKs Put the Mouths in Their Right Place.
AB - Plants have stomata, mouth-like pores on their surface, to adjust to
environmental changes such as temperature and humidity to ensure optimum
physiology and metabolism. A new study adds a key player, SERK, to the signal
sensing apparatus to inform where stomata are to be formed on the leaf.
PMID- 26439341
TI - Neural Evolution: Costing the Benefits of Eye Loss.
AB - What selective forces contribute to eye loss in cave animals? A new study shows
the eye and optic tectum of a cave fish consumes ~5-17% of the total energy
consumption, emphasising that selection to reduce energy consumption may drive
eye loss.
PMID- 26439342
TI - Circadian Clocks: Unexpected Biochemical Cogs.
AB - A circadian oscillation can be reconstituted in vitro from three proteins that
cycles with a period of ~ 24 h. Two recent studies provide surprising biochemical
answers to why this remarkable oscillator has such a long time constant and how
it can switch effortlessly between alternating enzymatic modes.
PMID- 26439343
TI - The tree view of life.
PMID- 26439344
TI - History of life on Earth.
PMID- 26439345
TI - Archaea.
AB - A headline on the front page of the New York Times for November 3, 1977, read
"Scientists Discover a Way of Life That Predates Higher Organisms". The
accompanying article described a spectacular claim by Carl Woese and George Fox
to have discovered a third form of life, a new 'domain' that we now call Archaea.
It's not that these microbes were unknown before, nor was it the case that their
peculiarities had gone completely unnoticed. Indeed, Ralph Wolfe, in the same
department at the University of Illinois as Woese, had already discovered how it
was that methanogens (uniquely on the planet) make methane, and the bizarre
adaptations that allow extremely halophilic archaea (then called halobacteria)
and thermoacidophiles to live in the extreme environments where they do were
already under investigation in many labs. But what Woese and Fox had found was
that these organisms were related to each other not just in their 'extremophily'
but also phylogenetically. And, most surprisingly, they were only remotely
related to the rest of the prokaryotes, which we now call the domain Bacteria
(Figure 1).
PMID- 26439346
TI - Photosynthesis and early Earth.
AB - Life has been built on the evolution and innovation of microbial metabolisms.
Even with our scant understanding of the full diversity of microbial life, it is
clear that microbes have become integral components of the biogeochemical cycles
that drive our planet. The antiquity of life further suggests that various
microbial metabolisms have been core and essential to global elemental cycling
for a majority of Earth's history.
PMID- 26439347
TI - The Neoproterozoic.
AB - The Neoproterozoic era was arguably the most revolutionary in Earth history.
Extending from 1000 to 541 million years ago, it stands at the intersection of
the two great tracts of evolutionary time: on the one side, some three billion
years of pervasively microbial 'Precambrian' life, and on the other the modern
'Phanerozoic' biosphere with its extraordinary diversity of large multicellular
organisms. The disturbance doesn't stop here, however: over this same stretch of
time the planet itself was in the throes of change. Tectonically, it saw major
super-continental reconfigurations, climatically its deepest ever glacial freeze,
and geochemically some of the most anomalous perturbations on record. What lies
behind this dramatic convergence of biological and geological phenomena, and how
exactly did it give rise to the curiously complex world that we now inhabit?
PMID- 26439348
TI - The Cambrian explosion.
AB - The sudden appearance of fossils that marks the so-called 'Cambrian explosion'
has intrigued and exercised biologists since Darwin's time. In On the Origin of
Species, Darwin made it clear that he believed that ancestral forms 'lived long
before' their first fossil representatives. While he considered such an invisible
record necessary to explain the level of complexity already seen in the fossils
of early trilobites, Darwin was at a loss to explain why there were no
corresponding fossils of these earlier forms. In chapter 9 of the Origin,
entitled 'On the imperfection of the geological record', he emphasized the
'poorness of our palaeontological collections' and stated categorically that 'no
organism wholly soft can be preserved'. Fortunately much has been discovered in
the last 150 years, not least multiple examples of Cambrian and Precambrian soft
bodied fossils. We now know that the sudden appearance of fossils in the Cambrian
(541-485 million years ago) is real and not an artefact of an imperfect fossil
record: rapid diversification of animals coincided with the evolution of
biomineralized shells. And although fossils in earlier rocks are rare, they are
not absent: their rarity reflects the low diversity of life at this time, as well
as the low preservation potential of Precambrian organisms (see Primer by
Butterfield, in this issue).
PMID- 26439349
TI - Insect evolution.
AB - It goes without saying that insects epitomize diversity, and with over a million
documented species they stand out as one of the most remarkable lineages in the
3.5-billion-year history of life on earth (Figure 1). This reality is passe to
even the layperson and is taken for granted in the same way none of us think much
of our breathing as we go about our day, and yet insects are just as vital to our
existence. Insects are simultaneously familiar and foreign to us, and while a
small fraction are beloved or reviled, most are simply ignored. These inexorable
evolutionary overachievers outnumber us all, their segmented body plan is
remarkably labile, they combine a capacity for high rates of speciation with low
levels of natural extinction, and their history of successes eclipses those of
the more familiar ages of dinosaurs and mammals alike. It is their evolution -
persisting over vast expanses of geological time and inextricably implicated in
the diversification of other lineages - that stands as one of the most expansive
subjects in biology.
PMID- 26439350
TI - Lobopodians.
PMID- 26439351
TI - Phylogenomic Insights into Animal Evolution.
AB - Animals make up only a small fraction of the eukaryotic tree of life, yet, from
our vantage point as members of the animal kingdom, the evolution of the
bewildering diversity of animal forms is endlessly fascinating. In the century
following the publication of Darwin's Origin of Species, hypotheses regarding the
evolution of the major branches of the animal kingdom - their relationships to
each other and the evolution of their body plans - was based on a consideration
of the morphological and developmental characteristics of the different animal
groups. This morphology-based approach had many successes but important aspects
of the evolutionary tree remained disputed. In the past three decades, molecular
data, most obviously primary sequences of DNA and proteins, have provided an
estimate of animal phylogeny largely independent of the morphological evolution
we would ultimately like to understand. The molecular tree that has evolved over
the past three decades has drastically altered our view of animal phylogeny and
many aspects of the tree are no longer contentious. The focus of molecular
studies on relationships between animal groups means, however, that the
discipline has become somewhat divorced from the underlying biology and from the
morphological characteristics whose evolution we aim to understand. Here, we
consider what we currently know of animal phylogeny; what aspects we are still
uncertain about and what our improved understanding of animal phylogeny can tell
us about the evolution of the great diversity of animal life.
PMID- 26439352
TI - The Origin and Diversification of Birds.
AB - Birds are one of the most recognizable and diverse groups of modern vertebrates.
Over the past two decades, a wealth of new fossil discoveries and phylogenetic
and macroevolutionary studies has transformed our understanding of how birds
originated and became so successful. Birds evolved from theropod dinosaurs during
the Jurassic (around 165-150 million years ago) and their classic small,
lightweight, feathered, and winged body plan was pieced together gradually over
tens of millions of years of evolution rather than in one burst of innovation.
Early birds diversified throughout the Jurassic and Cretaceous, becoming capable
fliers with supercharged growth rates, but were decimated at the end-Cretaceous
extinction alongside their close dinosaurian relatives. After the mass
extinction, modern birds (members of the avian crown group) explosively
diversified, culminating in more than 10,000 species distributed worldwide today.
PMID- 26439353
TI - The Evolutionary Origin of a Terrestrial Flora.
AB - Life on Earth as we know it would not be possible without the evolution of
plants, and without the transition of plants to live on land. Land plants (also
known as embryophytes) are a monophyletic lineage embedded within the green
algae. Green algae as a whole are among the oldest eukaryotic lineages documented
in the fossil record, and are well over a billion years old, while land plants
are about 450-500 million years old. Much of green algal diversification took
place before the origin of land plants, and the land plants are unambiguously
members of a strictly freshwater lineage, the charophyte green algae. Contrary to
single-gene and morphological analyses, genome-scale phylogenetic analyses
indicate the sister taxon of land plants to be the Zygnematophyceae, a group of
mostly unbranched filamentous or single-celled organisms. Indeed, several
charophyte green algae have historically been used as model systems for certain
problems, but often without a recognition of the specific phylogenetic
relationships among land plants and (other) charophyte green algae. Insight into
the phylogenetic and genomic properties of charophyte green algae opens up new
opportunities to study key properties of land plants in closely related model.
This review will outline the transition from single-celled algae to modern-day
land plants, and will highlight the bright promise studying the charophyte green
algae holds for better understanding plant evolution.
PMID- 26439354
TI - Endosymbiosis and Eukaryotic Cell Evolution.
AB - Understanding the evolution of eukaryotic cellular complexity is one of the grand
challenges of modern biology. It has now been firmly established that
mitochondria and plastids, the classical membrane-bound organelles of eukaryotic
cells, evolved from bacteria by endosymbiosis. In the case of mitochondria,
evidence points very clearly to an endosymbiont of alpha-proteobacterial
ancestry. The precise nature of the host cell that partnered with this
endosymbiont is, however, very much an open question. And while the host for the
cyanobacterial progenitor of the plastid was undoubtedly a fully-fledged
eukaryote, how - and how often - plastids moved from one eukaryote to another
during algal diversification is vigorously debated. In this article I frame
modern views on endosymbiotic theory in a historical context, highlighting the
transformative role DNA sequencing played in solving early problems in eukaryotic
cell evolution, and posing key unanswered questions emerging from the age of
comparative genomics.
PMID- 26439355
TI - Morphological Phylogenetics in the Genomic Age.
AB - Evolutionary trees underpin virtually all of biology, and the wealth of new
genomic data has enabled us to reconstruct them with increasing detail and
confidence. While phenotypic (typically morphological) traits are becoming less
important in reconstructing evolutionary trees, they still serve vital and unique
roles in phylogenetics, even for living taxa for which vast amounts of genetic
information are available. Morphology remains a powerful independent source of
evidence for testing molecular clades, and - through fossil phenotypes - the
primary means for time-scaling phylogenies. Morphological phylogenetics is
therefore vital for transforming undated molecular topologies into dated
evolutionary trees. However, if morphology is to be employed to its full
potential, biologists need to start scrutinising phenotypes in a more objective
fashion, models of phenotypic evolution need to be improved, and approaches for
analysing phenotypic traits and fossils together with genomic data need to be
refined.
PMID- 26439356
TI - Novelty and Innovation in the History of Life.
AB - The history of life as documented by the fossil record encompasses evolutionary
diversifications at scales ranging from the Ediacaran-Cambrian explosion of
animal life and the invasion of land by vascular plants, insects and vertebrates
to the diversification of flowering plants over the past 100 million years and
the radiation of horses. Morphological novelty and innovation has been a
recurrent theme. The architects of the modern synthesis of evolutionary theory
made three claims about evolutionary novelty and innovation: first, that all
diversifications in the history of life represent adaptive radiations; second,
that adaptive radiations are driven principally by ecological opportunity rather
than by the supply of new morphological novelties, thus the primary questions
about novelty and innovation focus on their ecological and evolutionary success;
and third, that the rate of morphological divergence between taxa was more rapid
early in the history of a clade but slowed over time as ecological opportunities
declined. These claims have strongly influenced subsequent generations of
evolutionary biologists, yet over the past two decades each has been challenged
by data from the fossil record, by the results of comparative phylogenetic
analyses and through insights from evolutionary developmental biology.
Consequently a broader view of novelty and innovation is required. An outstanding
issue for future work is identifying the circumstances associated with different
styles of diversification and whether their frequency has changed through the
history of life.
PMID- 26439357
TI - Life in the Aftermath of Mass Extinctions.
AB - The vast majority of species that have ever lived went extinct sometime other
than during one of the great mass extinction events. In spite of this, mass
extinctions are thought to have outsized effects on the evolutionary history of
life. While part of this effect is certainly due to the extinction itself, I here
consider how the aftermaths of mass extinctions might contribute to the
evolutionary importance of such events. Following the mass loss of taxa from the
fossil record are prolonged intervals of ecological upheaval that create a
selective regime unique to those times. The pacing and duration of ecosystem
change during extinction aftermaths suggests strong ties between the biosphere
and geosphere, and a previously undescribed macroevolutionary driver - earth
system succession. Earth system succession occurs when global environmental or
biotic change, as occurs across extinction boundaries, pushes the biosphere and
geosphere out of equilibrium. As species and ecosystems re-evolve in the
aftermath, they change global biogeochemical cycles - and in turn, species and
ecosystems - over timescales typical of the geosphere, often many thousands to
millions of years. Earth system succession provides a general explanation for the
pattern and timing of ecological and evolutionary change in the fossil record.
Importantly, it also suggests that a speed limit might exist for the pace of
global biotic change after massive disturbance - a limit set by geosphere
biosphere interactions. For mass extinctions, earth system succession may drive
the ever-changing ecological stage on which species evolve, restructuring
ecosystems and setting long-term evolutionary trajectories as they do.
PMID- 26439358
TI - The RNA World as a Model System to Study the Origin of Life.
AB - Understanding how life arose is a fundamental problem of biology. Much progress
has been made by adopting a synthetic and mechanistic perspective on originating
life. We present a current view of the biochemistry of the origin of life,
focusing on issues surrounding the emergence of an RNA World in which RNA
dominated informational and functional roles. There is cause for optimism on this
difficult problem: the prebiotic chemical inventory may not have been as
nightmarishly complex as previously thought; the catalytic repertoire of
ribozymes continues to expand, approaching the goal of self-replicating RNA;
encapsulation in protocells provides evolutionary and biophysical advantages.
Nevertheless, major issues remain unsolved, such as the origin of a genetic code.
Attention to this field is particularly timely given the accelerating discovery
and characterization of exoplanets.
PMID- 26439364
TI - Hierarchical CdS Nanowires Based Rigid and Flexible Photodetectors with Ultrahigh
Sensitivity.
AB - Hierarchical CdS nanowires were synthesized via a facile vapor transport method,
which were used to fabricate both rigid and flexible visible-light
photodetectors. Studies found that the rigid photodetectors on SiO2/Si substrate
showed ultrahigh photo-dark current ratio up to 1.96 * 10(4), several orders of
magnitude higher than previously reported CdS nanostructures, as well as high
specific detectivity (4.27 * 10(12) Jones), fast response speed and excellent
environmental stability. Highly flexible photodetectors were also fabricated on
polyimide substrate, which exhibited comparable photoresponse performance as the
rigid one. In addition, the as-prepared flexible devices displayed excellent
mechanical flexibility, electrical stability and folding endurance. The results
indicate that the hierarchical CdS nanowires may be good candidates for nanoscale
optoelectronic devices such as high-efficiency photoswitches and highly
photosensitive detectors.
PMID- 26439359
TI - Pineal hypoplasia, reduced melatonin and sleep disturbance in patients with PAX6
haploinsufficiency.
AB - In rodent studies, paired box 6 (PAX6) appears to play an important role in the
development of the pineal, the primary source of the circadian regulating
hormone, melatonin. Pineal hypoplasia has been previously reported in patients
with PAX6 haploinsufficiency (+/-); however, pineal measurement, melatonin
concentrations and sleep quality have not been reported. This cross-sectional
descriptive study examined pineal volume, melatonin secretion and sleep
disturbance in 37 patients with PAX6+/- (age 15.3 +/- 9.9 years) and 17 healthy
controls (16.0 +/- 7.2 years), within an inpatient setting at the Clinical
Research Center of the National Institutes of Health, Bethesda, Maryland, USA.
Pineal volume was evaluated by magnetic resonance imaging. Diurnal serum
cortisol, serum melatonin and urine 6-sulphatoxymelatonin concentrations were
measured by enzyme-linked immunosorbent assay. The Child Sleep Habits
Questionnaire was administered for patients <13 years old. Pineal volume was
fivefold lower in PAX6+/- versus controls (mean +/- SD: 25 +/- 15 versus 129 +/-
50 MUL, P < 0.001). Midnight serum cortisol was similar in PAX6+/- versus
controls (P = 0.14). Midnight serum melatonin was > twofold lower in PAX6+/-
versus controls [median (25th-75 th): 28 (22-42) versus 71 (46-88) pg mL-(1), P <
0.001]. First morning void urinary 6-sulphatoxymelatonin was fourfold lower in
PAX6+/- versus controls [11 (6-26) versus 45 (34-61) ng mg(-1) Cr, P = 0.001].
Child Sleep Habits Questionnaire score was higher in PAX6+/- versus controls (48
+/- 6 versus 41 +/- 5, P = 0.03). The current findings suggest that PAX6+/- is
associated with smaller pineal size, lower melatonin secretion and greater
parental report of sleep disturbances in children. Further studies are needed to
explore the potential use of melatonin replacement for improving sleep quality in
patients with PAX6+/-.
PMID- 26439365
TI - Exploration of Excited State Deactivation Pathways of Adenine Monohydrates.
AB - Binding of a single water molecule has a dramatic effect on the excited state
lifetime of adenine. Here we report a joint nonadiabatic dynamics and reaction
paths study aimed at understanding the sub-100 fs lifetime of adenine in the
monohydrates. Our nonadiabatic dynamics simulations, performed using the ADC(2)
electronic structure method, show a shortening of the excited state lifetime in
the monohydrates with respect to bare adenine. However, the computed lifetimes
were found to be significantly longer that the observed one. By comparing the
reaction pathways of several excited state deactivation processes in adenine and
adenine monohydrates, we show that electron-driven proton transfer from water to
nitrogen atom N3 of the adenine ring may be the process responsible for the
observed ultrafast decay. The inaccessibility of the electron-driven proton
transfer pathway to trajectory-based nonadiabatic dynamics simulation is
discussed.
PMID- 26439366
TI - Pseudomonas aeruginosa: arsenal of resistance mechanisms, decades of changing
resistance profiles, and future antimicrobial therapies.
AB - Antimicrobial resistance is one of the most serious public health issues facing
humans since the discovery of antimicrobial agents. The frequent, prolonged, and
uncontrolled use of antimicrobial agents are major factors in the emergence of
antimicrobial-resistant bacterial strains, including multidrug-resistant
variants. Pseudomonas aeruginosa is a leading cause of nosocomial infections. The
abundant data on the increased resistance to antipseudomonal agents support the
need for global action. There is a paucity of new classes of antibiotics active
against P. aeruginosa. Here, we discuss recent antibacterial resistance profiles
and mechanisms of resistance by P. aeruginosa. We also review future potential
methods for controlling antibiotic-resistant bacteria, such as phage therapy,
nanotechnology and antipseudomonal vaccines.
PMID- 26439367
TI - Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a
phytocannabinoid with therapeutic potential for anticipatory nausea.
AB - RATIONALE: Anticipatory nausea (AN) is a poorly controlled side effect
experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to
benzodiazepine anxiolytics, which have limited efficacy, have significant
sedative effects and induce dependency. The non-psychoactive phytocannabinoid,
cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN
models, however determination of its neuromotor tolerability profile is crucial
to justify clinical investigation. Provisional evidence for appetite-stimulating
properties also requires detailed investigation. OBJECTIVES: This study aims to
assess the tolerability of CBDA in locomotor activity, motor coordination and
muscular strength tests, and additionally for ability to modulate feeding
behaviours. METHODS: Male Lister Hooded rats administered CBDA (0.05-5 mg/kg;
p.o.) were assessed in habituated open field (for locomotor activity), static
beam and grip strength tests. A further study investigated whether these CBDA
doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like
effects in the habituated open field prompted testing of 5 mg/kg CBDA for
anxiolytic-like activity in unhabituated open field, light/dark box and novelty
suppressed feeding (NSF) tests. RESULTS: CBDA had no adverse effects upon
performance in any neuromotor tolerability test, however anxiolytic-like
behaviour was observed in the habituated open field. Normal feeding behaviours
were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding
latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635,
indicative of anxiolytic-like effects, but had no effect on anxiety-like
behaviour in the novel open field or light/dark box. CONCLUSIONS: CBDA is very
well tolerated and devoid of the sedative side effect profile of benzodiazepines,
justifying its clinical investigation as a novel AN treatment.
PMID- 26439368
TI - New development in a blood-based diagnostic test for early-stage arthritis.
PMID- 26439369
TI - Silver(I)-Ferrophox Catalyzed Enantioselective Desymmetrization of
Cyclopentenedione: Synthesis of Highly Substituted Bicyclic Pyrrolidines.
AB - A highly enantioselective desymmetrization of prochiral cyclopentene-1,3-dione
via [3 + 2] cycloaddition of azomethine ylide using a silver(I)-ferrophox complex
has been demonstrated. The method has been utilized in the synthesis of highly
functionalized enantioenriched 5,5-fused bicyclic pyrrolidine derivatives under
mild reaction conditions.
PMID- 26439370
TI - Near-infrared fluorescence cholangiography with indocyanine green for biliary
atresia. Real-time imaging during the Kasai procedure: a pilot study.
AB - INTRODUCTION: Hepatoportoenterostomy (HPE) with the Kasai procedure is the
treatment of choice for biliary atresia (BA) as the initial surgery. However, the
appropriate level of dissection level of the fibrous cone (FC) of the porta
hepatis (PH) is frequently unclear, and the procedure sometimes results in
unsuccessful outcomes. Recently, indocyanine green near-infrared fluorescence
imaging (ICG-FCG) has been developed as a form of real-time cholangiography.
METHODS: We applied this technique in five patients with BA to visualize the
biliary flow at the PH intraoperatively. ICG was injected intravenously the day
before surgery as the liver function test, and the liver was observed with a near
infrared camera system during the operation while the patient's feces was also
observed. RESULTS: In all patients, the whole liver fluoresced diffusely with ICG
containing stagnant bile, whereas no extrahepatic structures fluoresced. The
findings of the ICG fluorescence pattern of the PH after dissection of the FC
were classified into three types: spotty fluorescence, one patient; diffuse weak
fluorescence, three patients; and diffuse strong fluorescence, one patient. In
all five patients, the feces evacuated after HPE showed distinct fluorescent
spots, although that obtained before surgery showed no fluorescence. One patient
with diffuse strong fluorescence who did not achieve JF underwent living related
liver transplantation six months after the initial HPE procedure. Four patients,
including three cases involving diffuse weak fluorescence and one case involving
spotty fluorescence showed weak fluorescence compared to that of the surrounding
liver surface. CONCLUSION: We were able to detect the presence of bile excretion
at the time of HPE intraoperatively and successfully evaluated the extent of bile
excretion using this new technique. Furthermore, the ICG-FCG findings may provide
information leading to a new classification and potentially function as an
indicator predicting the clinical outcomes after HPE.
PMID- 26439371
TI - Laparoscopic modified bypass pyeloplasty: a simple procedure for straightforward
ureteral spatulation and intracorporeal suturing.
AB - PURPOSE: Bypass pyeloplasty (BP) is a simple, non-dismembered procedure that is a
side-to-side anastomosis without dividing the ureteropelvic junction (UPJ). BP
has been considered more suitable especially for novice surgeons than dismembered
pyeloplasty via the laparoscopic approach, but not reported. However, the
disadvantage of laparoscopic BP is that it is difficult to suture the side of the
anastomosis that is far from the camera. To overcome this disadvantage, a
modified technique was developed. This procedure and its initial results are
reported. METHODS: Twenty-six consecutive patients underwent laparoscopic
modified BP. The patients' median age at surgery was 10.5 years. Ten patients
were adults and 16 were children. The key step of modified BP involves dividing
the UPJ after ureteral spatulation and suture of the dependent portion. This
provides both better visualization of the anastomosis portion and easy
anastomosis. RESULTS: All procedures were completed by laparoscopic modified BP.
The median operative time was 246 (range 170-357) min. The median time for
ureteropelvic anastomosis was 205 (range 145-311) min. There were no significant
differences in mean operative time and ureteropelvic anastomotic time between
adults and children (adults/children = 243 +/- 49 min:252 +/- 58 min, p = 0.66,
192 +/- 33 min:214 +/- 48 min, p = 0.21, respectively). Successful resolution of
UPJO was observed in 96 % of cases. CONCLUSIONS: Laparoscopic modified BP
combines the advantages of non-dismembered and dismembered pyeloplasty. Because
there were no differences in mean operative and anastomotic times between adults
and children, laparoscopic modified BP might be an efficient procedure for all
ages, especially children.
PMID- 26439372
TI - A safe method of ciliary sulcus fixation of foldable intraocular lens using a
ciliary sulcus guide.
AB - To describe a novel technique for implantation of intraocular lens in the absence
of capsular support using a ciliary sulcus guide. Based on the anatomic knowledge
of the ciliary sulcus and the sclera, a new instrument was developed to pierce
the needle safely through the ciliary sulcus and sclera. While the foldable lens
is stored inside the cartridge, the leading haptic is sutured with a cow-hitch
knot. The needle is then inserted into the ciliary sulcus guide. The tip of the
guide is inserted from the corneal incision and proceeded under the iris to touch
and fit the ciliary sulcus. The needle is pushed from back side. The needle comes
out at precise point at the sclera. Implantation of the lens was performed
through a 2.8 mm clear cornea incision using the injector. The trailing haptic is
tied after implantation, and then the same procedure is performed at the opposite
side. We performed this technique to 15 aphakic eyes without sufficient capsular
support. There was no bleeding or other intraoperative complication. All the
points coming out the sclera were between 2 and 2.5 mm from the limbus. The ab
interno technique for scleral fixation of IOL is quicker, easier and less
traumatic then ab externo techniques. A new ciliary sulcus guide which is usable
with both straight and curved needles eliminates the blind maneuvers of ab
interno technique and makes this technique more safe and precise.
PMID- 26439374
TI - Non-pharmacological interventions for sleep promotion in the intensive care unit.
AB - BACKGROUND: Adults in intensive care units (ICUs) often suffer from a lack of
sleep or frequent sleep disruptions. Non-pharmacological interventions can
improve the duration and quality of sleep and decrease the risk of sleep
disturbance, delirium, post-traumatic stress disorder (PTSD), and the length of
stay in the ICU. However, there is no clear evidence of the effectiveness and
harms of different non-pharmacological interventions for sleep promotion in
adults admitted to the ICU. OBJECTIVES: To assess the efficacy of non
pharmacological interventions for sleep promotion in critically ill adults in the
ICU.To establish whether non-pharmacological interventions are safe and
clinically effective in improving sleep quality and reducing length of ICU stay
in critically ill adults.To establish whether non-pharmacological interventions
are cost effective. SEARCH METHODS: We searched the Cochrane Central Register of
Controlled Trials (CENTRAL, 2014, Issue 6), MEDLINE (OVID, 1950 to June 2014),
EMBASE (1966 to June 2014), CINAHL (Cumulative Index to Nursing and Allied Health
Literature, 1982 to June 2014), Institute for Scientific Information (ISI) Web of
Science (1956 to June 2014), CAM on PubMed (1966 to June 2014), Alt HealthWatch
(1997 to June 2014), PsycINFO (1967 to June 2014), the China Biological Medicine
Database (CBM-disc, 1979 to June 2014), and China National Knowledge
Infrastructure (CNKI Database, 1999 to June 2014). We also searched the following
repositories and registries to June 2014: ProQuest Dissertations & Theses Global,
the US National Institutes of Health Ongoing Trials Register
(www.clinicaltrials.gov), the metaRegister of Controlled Trials (ISRCTN Register)
(www.controlled-trials.com), the Chinese Clinical Trial Registry
(www.chictr.org.cn), the Clinical Trials Registry-India (www.ctri.nic.in), the
Grey Literature Report from the New York Academy of Medicine Library
(www.greylit.org), OpenGrey (www.opengrey.eu), and the World Health Organization
International Clinical Trials Registry platform (www.who.int/trialsearch). We
handsearched critical care journals and reference lists and contacted relevant
experts to identify relevant unpublished data. SELECTION CRITERIA: We included
all randomized controlled trials (RCT) and quasi-RCTs that evaluated the effects
of non-pharmacological interventions for sleep promotion in critically ill adults
(aged 18 years and older) during admission to critical care units or ICUs. DATA
COLLECTION AND ANALYSIS: Two authors independently screened the search results
and assessed the risk of bias in selected trials. One author extracted the data
and a second checked the data for accuracy and completeness. Where possible, we
combined results in meta-analyses using mean differences and standardized mean
differences for continuous outcomes and risk ratios for dichotomous outcomes. We
used post-test scores in this review. MAIN RESULTS: We included 30 trials, with a
total of 1569 participants, in this review. We included trials of ventilator mode
or type, earplugs or eye masks or both, massage, relaxation interventions, foot
baths, music interventions, nursing interventions, valerian acupressure,
aromatherapy, and sound masking. Outcomes included objective sleep outcomes,
subjective sleep quality and quantity, risk of delirium, participant
satisfaction, length of ICU stay, and adverse events. Clinical heterogeneity
(e.g., participant population, outcomes measured) and research design limited
quantitative synthesis, and only a small number of studies were available for
most interventions. The quality of the evidence for an effect of non
pharmacological interventions on any of the outcomes examined was generally low
or very low. Only three trials, all of earplugs or eye masks or both, provided
data suitable for two separate meta-analyses. These meta-analyses, each of two
studies, showed a lower incidence of delirium during ICU stay (risk ratio 0.55,
95% confidence interval (CI) 0.38 to 0.80, P value = 0.002, two studies, 177
participants) and a positive effect of earplugs or eye masks or both on total
sleep time (mean difference 2.19 hours, 95% CI 0.41 to 3.96, P value = 0.02, two
studies, 116 participants); we rated the quality of the evidence for both of
these results as low.There was also some low quality evidence that music (350
participants; four studies) may improve subjective sleep quality and quantity,
but we could not pool the data. Similarly, there was some evidence that
relaxation techniques, foot massage, acupressure, nursing or social intervention,
and sound masking can provide small improvements in various subjective measures
of sleep quality and quantity, but the quality of the evidence was low. The
effects of non-pharmacological interventions on objective sleep outcomes were
inconsistent across 16 studies (we rated the quality of the evidence as very
low): the majority of studies relating to the use of earplugs and eye masks found
no benefit; results from six trials of ventilator modes suggested that certain
ventilator settings might offer benefits over others, although the results of the
individual trials did not always agree with each other. Only one study measured
length of stay in the ICU and found no significant effect of earplugs plus eye
masks. No studies examined the effect of any non-pharmacological intervention on
mortality, risk of post-traumatic stress disorder, or cost-effectiveness; the
included studies did not clearly report adverse effects, although there was very
low quality evidence that ventilator mode influenced the incidence of central
apnoeas and patient-ventilator asynchronies. AUTHORS' CONCLUSIONS: The quality of
existing evidence relating to the use of non-pharmacological interventions for
promoting sleep in adults in the ICU was low or very low. We found some evidence
that the use of earplugs or eye masks or both may have beneficial effects on
sleep and the incidence of delirium in this population, although the quality of
the evidence was low. Further high-quality research is needed to strengthen the
evidence base.
PMID- 26439376
TI - Disability and Violent Victimization in a National Sample of Adolescents: A
Longitudinal Study.
AB - In the victimization literature, a significant association has been consistently
observed between disability and the victimization of children and adolescents. It
is largely unknown, however, whether individuals with disabilities continue to
suffer from a heightened risk of violent victimization when they reach young
adulthood and adulthood. In addition, despite the close nexus between
victimization and perpetration, prior studies have generally failed to control
for violent acts perpetrated by individuals with disabilities. This study
addresses these issues by drawing on the panel design nature of the National
Longitudinal Study of Adolescent Health. The results show that although physical
disability is not linked to victimization risk, learning disability is
significantly associated with an elevated risk of violent victimization.
PMID- 26439377
TI - In vitro and in vivo insulinotropic properties of the multifunctional frog skin
peptide hymenochirin-1B: a structure-activity study.
AB - Hymenochirin-1b (Hym-1B; IKLSPETKDNLKKVLKGAIKGAIAVAKMV.NH2) is a cationic, alpha
helical amphibian host-defense peptide with antimicrobial, anticancer, and
immunomodulatory properties. This study investigates the abilities of the peptide
and nine analogues containing substitutions of Pro(5), Glu(6), and Asp(9) by
either L-lysine or D-lysine to stimulate insulin release in vitro using BRIN-BD11
clonal beta cells or isolated mouse islets and in vivo using mice fed a high-fat
diet to produce obesity and insulin resistance. Hym-1B produced a significant and
concentration-dependent increase in the rate of insulin release from BRIN-BD11
cells without cytotoxicity at concentrations up to 1 uM with a threshold
concentration of 1 nM. The threshold concentrations for the analogues were:
[P5K], [E6K], [D9K], [P5K, E6K] and [E6K, D9k] 0.003 nM, [E6K, D9K] and [D9k]
0.01 nM, [P5K, D9K] 0.1 nM and [E6k] 0.3 nM. All peptides displayed cytotoxicity
at concentrations >=1 uM except the [P5K] and [D9k] analogues which were non
toxic at 3 uM. The potency and maximum rate of insulin release from mouse islets
produced by the [P5K] peptide were significantly greater than produced by Hym-1B.
Neither Hym-1B nor the [P5K] analogue at 1 uM concentration had an effect on
membrane depolarization or intracellular Ca(2+). The [P5K] analogue (1 uM)
produced a significant increase in cAMP concentration in BRIN-BD11 cells and
stimulated GLP-1 secretion from GLUTag cells. Down-regulation of the protein
kinase A pathway by overnight incubation with forskolin completely abolished the
insulin-releasing effects of [P5K]hym-1B. Intraperitoneal administration of the
[P5K] and [D9k] analogues (75 nmol/kg body weight) to high-fat-fed mice with
insulin resistance significantly enhanced glucose tolerance with a concomitant
increase in insulin secretion. We conclude that [P5K]hym-1B and [D9k]hym-1B show
potential for development into anti-diabetic agents.
PMID- 26439378
TI - Drug response to HER2 gatekeeper T798M mutation in HER2-positive breast cancer.
AB - The gatekeeper T798M mutation in HER2 kinase domain has been observed to
considerably shift drug sensitivity to HER2 in breast cancer therapy. Here, drug
response of clinical tyrosine kinase inhibitors (TKIs) to the mutation was
profiled using a synthetic biology protocol. It was found that TKIs can be
grouped into three classes in terms of their response behavior to T798M mutation:
class I inhibitors exhibit drug resistance upon the mutation, such as lapatinib,
TAK-285 and AEE788; class II inhibitors are insensitive to the mutation, such as
erlotinib and gefitinib; and class III inhibitors can be sensitized by the
mutation, such as staurosporine. However, kinetic study indicated that the
mutation has only a modest effect on the binding of substrate ATP to HER2.
Binding free energy analysis revealed that the drug response is primarily
determined by direct interaction between the kinase and inhibitors, but not by
indirect kinase interaction with competitive ATP. This is different to the
molecular mechanism of "generic" drug resistance conferring from EGFR gatekeeper
T790M mutation, which is caused by increased ATP affinity upon the mutation.
Structural analysis of kinase-inhibitor complexes unraveled that HER2 T798M
mutation induces significant steric hindrance to class I inhibitors, but can
establish additional nonbonded interactions for class III inhibitors.
PMID- 26439380
TI - Breast cancer prevention with anti-estrogens: review of the current evidence and
future directions.
AB - There is a potential for reducing the incidence of breast cancer by modifying or
changing the reversible risk factors like dietary modifications, modifications in
the sedentary life habits, etc. One of such methods which has gained popularity
now is chemoprevention. Many agents have been evaluated in the chemoprevention
setting in females with increased risk of breast cancers. Metformin, NSAIDS,
Bisphosphonates, and statins were evaluated by various investigators with
variable results. One of the agents that have been proven to be beneficial in
this setting is the anti-estrogens. A major disadvantage of chemoprevention is
that unlike prophylactic mastectomy it can never reduce the risk to near zero
although it reduces the risk significantly. Another issue is the compliance as
chemoprevention with anti-estrogens will need to be continued for 5 years while
surgery is a one-time procedure. Another disadvantage is the possible side
effects peculiar to each drug used which may not be a significant concern in
prophylactic mastectomy group. All these factors must also be kept in mind and
properly explained to the patient before starting chemoprevention using anti
estrogens. Here in this review we intend to look into the large randomized
controlled trials to quantify the present status of chemoprevention with anti
estrogens.
PMID- 26439379
TI - The influence of familial factors on the choice of the place of death for
terminally ill breast cancer patients: a retrospective single-center study.
AB - BACKGROUND: The social or familial factors influencing the location chosen for
end-of-life (EOL) care for terminally ill breast cancer patients are unknown.
METHODS: We retrospectively analyzed 195 patients with recurrent or progressive
breast cancer who received anticancer treatment at the National Cancer Center
Hospital between January 2008 and May 2012. Detailed data concerning the
patients' demographic, familial, and clinical characteristics were collected, and
multivariate and Cox logistic regression analyses were performed to evaluate the
impact of these characteristics on the place of EOL care and on survival,
respectively. RESULTS: Sixty-eight patients (34.9 %) died in a hospital, 26
patients (13.3 %) at home, and 101 patients (51.8 %) in hospice. Most of the
patients having caregivers received EOL care at palliative care facilities
(hospice or home) [odds ratio (OR) 2.57; 95 % confidence interval (CI) 1-6.6; p =
0.05]. In contrast, patients with factors suggesting a clinically severe status
(performance status >=2, use of opioids, delirium, and ascites) more often
received EOL care in a hospital. Among patients who received EOL care at hospice
or home, patients with minor children received EOL care at home (OR 0.08; 95 % CI
0.02-0.38; p = 0.001). Patients with brain metastases chose hospice (OR 12.37; 95
% CI 2.25-68.13; p = 0.004). Furthermore, having a caregiver was associated with
prolonged survival (hazard ratio 0.62; 95 % CI 0.39-0.97; p = 0.035). CONCLUSION:
Familial factors such as having children and caregivers significantly influenced
the place of EOL care for terminally ill breast cancer patients.
PMID- 26439381
TI - National Trend and Characteristics of Acute Hepatitis C among HIV-Infected
Individuals: A Matched Case-Control Study-Taiwan, 2001-2014.
AB - BACKGROUND: Hepatitis C virus (HCV) infection has been increasingly recognized
among HIV-infected men who have sex with men (MSM) worldwide. We investigated the
trend of and factors associated with acute hepatitis C (AHC) among HIV-infected
individuals in Taiwan. METHODS: The National Disease Surveillance System collects
characteristics of AHC, HIV, syphilis, and gonorrhea cases through mandatory
reports and patient interviews. Reported AHC patients in 2014 were interviewed
additionally on sexual and parenteral exposures. Information on HCV genotypes
were collected from the largest medical center serving HIV-infected Taiwanese. We
defined an HIV/AHC case as a documented negative HCV antibody test result
followed within 12 months by a positive test in a previously reported HIV
infected individual. Each case was matched to two HIV-infected, non-AHC controls
for age, age of HIV diagnosis, sex, transmission route, HIV diagnosis date, and
county/city. Conditional logistic regression was used to identify associated
characteristics. RESULTS: During 2001-2014, 93 of 6,624 AHC reports were HIV/AHC
cases; the annual case count increased from one in 2009 to 34 in 2014. All were
males (81 [87%] MSM) aged 21-49 years with AHC diagnosed 2-5,923 days after HIV
diagnoses. Sixty-eight (73%) lived in the Taipei metropolitan area. Detected HCV
genotypes were 2a (n = 6), 1b (n = 5), 1b + 2a (n = 1) and 2b (n = 1). Among 28
HIV/AHC patients interviewed in 2014, 13 (46%) reported engaging in unprotected
sex <=3 months before AHC diagnosis. Seventy-nine HIV/AHC cases were matched to
158 controls. HIV/AHC was associated with recent syphilis (adjusted odds ratio
[aOR], 10.9; 95% confidence interval [CI], 4.2-28.6) and last syphilis >6 months
(aOR, 2.9; 95% CI, 1.2-6.9). CONCLUSIONS: HIV/AHC cases continued to increase
particularly among sexually active HIV-infected MSM with a syphilis diagnosis in
northern Taiwan. We recommend surveillance of associated behavioral and virologic
characteristics and HCV counseling and testing for HIV-infected men in Taiwan.
PMID- 26439382
TI - Analyzing and Quantifying the Gain-of-Function Enhancement of IP3 Receptor Gating
by Familial Alzheimer's Disease-Causing Mutants in Presenilins.
AB - Familial Alzheimer's disease (FAD)-causing mutant presenilins (PS) interact with
inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) Ca(2+) release channels
resulting in enhanced IP3R channel gating in an amyloid beta (Abeta) production
independent manner. This gain-of-function enhancement of IP3R activity is
considered to be the main reason behind the upregulation of intracellular Ca(2+)
signaling in the presence of optimal and suboptimal stimuli and spontaneous
Ca(2+) signals observed in cells expressing mutant PS. In this paper, we employed
computational modeling of single IP3R channel activity records obtained under
optimal Ca(2+) and multiple IP3 concentrations to gain deeper insights into the
enhancement of IP3R function. We found that in addition to the high occupancy of
the high-activity (H) mode and the low occupancy of the low-activity (L) mode,
IP3R in FAD-causing mutant PS-expressing cells exhibits significantly longer mean
life-time for the H mode and shorter life-time for the L mode, leading to shorter
mean close-time and hence high open probability of the channel in comparison to
IP3R in cells expressing wild-type PS. The model is then used to extrapolate the
behavior of the channel to a wide range of IP3 and Ca(2+) concentrations and
quantify the sensitivity of IP3R to its two ligands. We show that the gain-of
function enhancement is sensitive to both IP3 and Ca(2+) and that very small
amount of IP3 is required to stimulate IP3R channels in the presence of FAD
causing mutant PS to the same level of activity as channels in control cells
stimulated by significantly higher IP3 concentrations. We further demonstrate
with simulations that the relatively longer time spent by IP3R in the H mode
leads to the observed higher frequency of local Ca(2+) signals, which can account
for the more frequent global Ca(2+) signals observed, while the enhanced activity
of the channel at extremely low ligand concentrations will lead to spontaneous
Ca(2+) signals in cells expressing FAD-causing mutant PS.
PMID- 26439383
TI - Intracerebroventricular Injection of Alarin Increased Glucose Uptake in Skeletal
Muscle of Diabetic Rats.
AB - In order to investigate the central effect of alarin on glucose uptake, we
administered alarin and/ or its inhibitor, ala6-25Cys into the cerebral
ventricles of the type 2 diabetic rats. Then the relative parameters about
glucose uptake in skeletal muscles were measured. We found that central treatment
with alarin significantly increased the food intake, body weight and glucose
infusion rates in hyperinsulinemic euglycemic clamp tests of the animals.
Besides, the treatment also enhanced 2-deoxy-[3H]-D-glucose uptake, vesicle
associated membrane protein 2 contents, glucose transporter 4 protein and mRNA
expression, as well as pAktThr308, pAktSer473 and total Akt levels in muscle
cells, but reduced plasma glucose and insulin levels of the rats. All of the
alarin-inducing events may be antagonised by central injection of ala6-25Cys.
These results suggest that central administration of alarin stimulates glucose
uptake mediated by activation of Akt signal pathway in type 2 diabetic animals.
PMID- 26439384
TI - Use of oral combination therapy for type 2 diabetes in primary care: Meeting
individualized patient goals.
AB - The management of type 2 diabetes mellitus (T2DM) by primary care physicians
(PCPs) has become increasingly complex due to limitations on consultation time,
an increasing array of drug treatment options, and issues of comorbidities and
polypharmacy. Diabetes is a progressive condition and treatment with a single
glucose-lowering agent can only address limited pathophysiologic targets and does
not provide adequate glycemic control in many cases. Consequently, most patients
with T2DM will eventually require treatment with multiple glucose-lowering
medications. Oral combination therapy in T2DM may be given as multiple-pills, or
as single-pill, fixed-dose combinations (FDCs), the latter of which offer
convenience, ease of administration, and a reduction in the medication burden.
Therefore, FDCs can potentially improve patients' treatment adherence and
optimize achievement and maintenance of glycemic targets. However, cost factors
also need to be considered. An understanding of the issues associated with the
use of combination therapy in T2DM will help PCPs to guide patient-centered
decision making and promote the effective management of T2DM.
PMID- 26439385
TI - Precritical State Transition Dynamics in the Attractor Landscape of a Molecular
Interaction Network Underlying Colorectal Tumorigenesis.
AB - From the perspective of systems science, tumorigenesis can be hypothesized as a
critical transition (an abrupt shift from one state to another) between
proliferative and apoptotic attractors on the state space of a molecular
interaction network, for which an attractor is defined as a stable state to which
all initial states ultimately converge, and the region of convergence is called
the basin of attraction. Before the critical transition, a cellular state might
transit between the basin of attraction for an apoptotic attractor and that for a
proliferative attractor due to the noise induced by the inherent stochasticity in
molecular interactions. Such a flickering state transition (state transition
between the basins of attraction for alternative attractors from the impact of
noise) would become more frequent as the cellular state approaches near the
boundary of the basin of attraction, which can increase the variation in the
estimate of the respective basin size. To investigate this for colorectal
tumorigenesis, we have constructed a stochastic Boolean network model of the
molecular interaction network that contains an important set of proteins known to
be involved in cancer. In particular, we considered 100 representative sequences
of 20 gene mutations that drive colorectal tumorigenesis. We investigated the
appearance of cancerous cells by examining the basin size of apoptotic,
quiescent, and proliferative attractors along with the sequential accumulation of
gene mutations during colorectal tumorigenesis. We introduced a measure to detect
the flickering state transition as the variation in the estimate of the basin
sizes for three-phenotype attractors from the impact of noise. Interestingly, we
found that this measure abruptly increases before a cell becomes cancerous during
colorectal tumorigenesis in most of the gene mutation sequences under a certain
level of stochastic noise. This suggests that a frequent flickering state
transition can be a precritical phenomenon of colorectal tumorigenesis.
PMID- 26439386
TI - Rosuvastatin 1.2 mg In Situ Gel Combined With 1:1 Mixture of Autologous Platelet
Rich Fibrin and Porous Hydroxyapatite Bone Graft in Surgical Treatment of
Mandibular Class II Furcation Defects: A Randomized Clinical Control Trial.
AB - BACKGROUND: A wide range of regenerative materials have been tried and tested in
the treatment of furcation defects. Rosuvastatin (RSV) is a new synthetic, second
generation, sulfur-containing, hydrophilic statin with potent anti-inflammatory
and osseodifferentiation mechanisms of action. Platelet-rich fibrin (PRF) is a
platelet concentrate having sustained release of various growth factors with
regenerative potential to treat periodontal defects. Porous hydroxyapatite (HA)
bone grafting material has a clinically satisfactory response when used to fill
periodontal intrabony defects. This double-masked randomized study is designed to
evaluate the potency of a combination of 1.2 mg RSV in situ gel with a 1:1
mixture of autologous PRF and HA bone graft in the surgical treatment of
mandibular Class II furcation defects compared with autologous PRF and HA bone
graft placed after open-flap debridement (OFD). METHODS: One hundred five
mandibular furcation defects were treated with OFD + placebo gel (group 1), PRF +
HA with OFD (group 2), or 1.2 mg RSV gel + PRF + HA with OFD (group 3). Clinical
and radiologic parameters (i.e., probing depth [PD], relative vertical and
relative horizontal clinical attachment level [rvCAL and rhCAL], intrabony defect
depth, and percentage of defect fill) were recorded at baseline and 9 months
postoperatively. RESULTS: Mean PD reduction was greater in group 2 (3.68 +/- 1.07
mm) and group 3 (4.62 +/- 1.03 mm) than group 1 (2.11 +/- 1.25 mm), and mean
rvCAL and rhCAL gain were greater in group 2 (3.31 +/- 0.52 and 2.97 +/- 0.56 mm,
respectively) and group 3 (4.17 +/- 0.70 and 4.05 +/- 0.76 mm) compared with
group 1 (1.82 +/- 0.78 and 1.62 +/- 0.64 mm). A significantly greater percentage
of mean bone fill was found in group 2 (54.69% +/- 1.93%) and group 3 (61.94% +/-
3.54%) compared with group 1 (10.09% +/- 4.28%). CONCLUSIONS: Treatment of
furcation defects with 1.2 mg RSV in situ gel combined with autologous PRF and
porous HA bone graft results in significant improvements of clinical and
radiographic parameters compared with OFD alone. These results imply that the
combination of RSV, PRF, and HA has synergistic effects, explaining their role as
a regenerative material in the treatment of furcation defects.
PMID- 26439388
TI - Colonization of C57BL/6 Mice by a Potential Probiotic Bifidobacterium bifidum
Strain under Germ-Free and Specific Pathogen-Free Conditions and during
Experimental Colitis.
AB - The effects of at least some probiotics are restricted to live, metabolically
active bacteria at their site of action. Colonization of and persistence in the
gastrointestinal tract is thus contributing to the beneficial effects of these
strains. In the present study, colonization of an anti-inflammatory
Bifidobacterium bifidum strain was studied in C57BL/6J mice under germ-free (GF)
and specific pathogen-free (SPF) conditions as well as during dextran sulfate
sodium (DSS)-induced colitis. B. bifidum S17/pMGC was unable to stably colonize
C57BL/6J mice under SPF conditions. Mono-association of GF mice by three doses on
consecutive days led to long-term, stable detection of up to 109 colony forming
units (CFU) of B. bifidum S17/pMGC per g feces. This stable population was
rapidly outcompeted upon transfer of mono-associated animals to SPF conditions. A
B. animalis strain was isolated from the microbiota of these re-conventionalized
mice. This B. animalis strain displayed significantly higher adhesion to murine
CMT-93 intestinal epithelial cells (IECs) than to human Caco-2 IECs (p = 0.018).
Conversely, B. bifidum S17/pMGC, i.e., a strain of human origin, adhered at
significantly higher levels to human compared to murine IECs (p < 0.001).
Disturbance of the gut ecology and induction of colitis by DSS-treatment did not
promote colonization of the murine gastrointestinal tract (GIT) by B. bifidum
S17/pMGC. Despite its poor colonization of the mouse GIT, B. bifidum S17/pMGC
displayed a protective effect on DSS-induced colitis when administered as viable
bacteria but not as UV-inactivated preparation. Collectively, these results
suggest a selective disadvantage of B. bifidum S17/pMGC in the competition with
the normal murine microbiota and an anti-inflammatory effect that requires live,
metabolically active bacteria.
PMID- 26439389
TI - Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.
AB - BACKGROUND: Carnosine is a naturally present dipeptide abundant in skeletal
muscle and an over-the counter food additive. Animal data suggest a role of
carnosine supplementation in the prevention and treatment of obesity, insulin
resistance, type 2 diabetes and cardiovascular disease but only limited human
data exists. METHODS AND RESULTS: Samples of vastus lateralis muscle were
obtained by needle biopsy. We measured muscle carnosine levels (high-performance
liquid chromatography), % body fat (bioimpedance), abdominal subcutaneous and
visceral adiposity (magnetic resonance imaging), insulin sensitivity (euglycaemic
hyperinsulinemic clamp), resting energy expenditure (REE, indirect calorimetry),
free-living ambulatory physical activity (accelerometers) and lipid profile in 36
sedentary non-vegetarian middle aged men (45+/-7 years) with varying degrees of
adiposity and glucose tolerance. Muscle carnosine content was positively related
to % body fat (r = 0.35, p = 0.04) and subcutaneous (r = 0.38, p = 0.02) but not
visceral fat (r = 0.17, p = 0.33). Muscle carnosine content was inversely
associated with insulin sensitivity (r = -0.44, p = 0.008), REE (r = -0.58,
p<0.001) and HDL-cholesterol levels (r = -0.34, p = 0.048). Insulin sensitivity
and physical activity were the best predictors of muscle carnosine content after
adjustment for adiposity. CONCLUSION: Our data shows that higher carnosine
content in human skeletal muscle is positively associated with insulin resistance
and fasting metabolic preference for glucose. Moreover, it is negatively
associated with HDL-cholesterol and basal energy expenditure. Intervention
studies targeting insulin resistance, metabolic and cardiovascular disease risk
factors are necessary to evaluate its putative role in the prevention and
management of type 2 diabetes and cardiovascular disease.
PMID- 26439390
TI - Evaluation of nonuniform field exposures with coupling factors.
AB - In this study, the safety compliance for nonuniform field exposures is discussed
using coupling factor concepts. The coupling factor, which is defined in the
International Electrotechnical Commission 62311 standard, is extended to consider
the effects of harmonics and also to apply to the specific absorption rate (for
frequencies up to 30 MHz). The proposed compliance procedure is applied to and
demonstrated for a prototype wireless power transfer (WPT) system with induction
coupling operating at the fundamental frequency in 140 kHz band. First,
measurements confirm that the perturbation of the external magnetic field
strength and S11 parameter of a one-loop antenna by a human-equivalent phantom
are sufficiently small, suggesting the applicability of the magneto-quasi-static
approximation to frequencies up to 30 MHz. Then, the frequency characteristics of
the coupling factor are derived for the WPT system. For the prototype system that
is not optimized for commercial usage, the maximum allowable transmitting power
is relaxed by a factor of 23 with the proposed procedure. The contribution of the
harmonics decreased the allowable transmitting power by 39%, indicating their
importance for safety compliance.
PMID- 26439392
TI - Acute Coronary Syndrome: Foreword.
PMID- 26439393
TI - Acute Coronary Syndrome: Out-of-Hospital Evaluation and Management.
AB - Identifying acute coronary syndrome (ACS) in family medicine settings can be
challenging, partly because it is uncommon in office practice and partly because
symptoms can be atypical. Initial evaluation includes review of the patient's
symptoms, an assessment of risk factors, and an electrocardiogram (ECG). When
symptoms are typical, such as chest pain and diaphoresis, patients should be
transported rapidly by emergency medical services (EMS) to the nearest emergency
department. If not contraindicated, aspirin and nitroglycerin should be
administered before transport. Oxygen should be administered if hypoxemia is
present. Patients with atypical symptoms and ECG results consistent with ACS also
should be transported by EMS. When patients have atypical symptoms and
nondiagnostic ECG results, consider risk factors for ACS. These include older
age; female sex; nonwhite race; and history of heart failure, stroke, diabetes,
or hypertension. If any of these risk factors is present and there is concern
about ACS, the patient should be transported to an emergency department. Family
practices in remote or rural areas are not always able to easily transport
patients to emergency departments. These remote or rural practices should have
ECG capabilities and consider acquiring the ability to obtain point-of-care
troponin assays.
PMID- 26439391
TI - Antioxidant Capacity of Melatonin on Preimplantation Development of Fresh and
Vitrified Rabbit Embryos: Morphological and Molecular Aspects.
AB - Embryo cryopreservation remains an important technique to enhance the
reconstitution and distribution of animal populations with high genetic merit.
One of the major detrimental factors to this technique is the damage caused by
oxidative stress. Melatonin is widely known as an antioxidant with multi-faceted
ways to counteract the oxidative stress. In this paper, we investigated the role
of melatonin in protecting rabbit embryos during preimplantation development from
the potential harmful effects of oxidative stress induced by in vitro culture or
vitrification. Rabbit embryos at morula stages were cultured for 2 hr with 0 or
10-3 M melatonin (C or M groups). Embryos of each group were either transferred
to fresh culture media (CF and MF groups) or vitrified/devitrified (CV and MV
groups), then cultured in vitro for 48 hr until the blastocyst stage. The culture
media were used to measure the activity of antioxidant enzymes: glutathione-s
transferase (GST) and superoxide dismutase (SOD), as well as the levels of two
oxidative substrates: lipid peroxidation (LPO) and nitric oxide (NO). The
blastocysts from each group were used to measure the expression of developmental
related genes (GJA1, POU5F1 and Nanog) and oxidative-stress-response-related
genes (NFE2L2, SOD1 and GPX1). The data showed that melatonin promoted
significantly (P<0.05) the blastocyst rate by 17% and 12% in MF and MV groups
compared to their controls (CF and CV groups). The GST and SOD activity
significantly increased by the treatment of melatonin in fresh or vitrified
embryos, while the levels of LPO and NO decreased (P<0.05). Additionally,
melatonin considerably stimulated the relative expression of GJA1, NFE2L2 and
SOD1 genes in MF and MV embryos compared to CF group. Furthermore, melatonin
significantly ameliorated the reduction of POU5F1 and GPX1 expression induced by
vitrification. The results obtained from the current investigation provide new
and clear molecular aspects regarding the mechanisms by which melatonin promotes
development of both fresh and vitrified rabbit embryos.
PMID- 26439394
TI - Acute Coronary Syndrome: Emergency Department Evaluation and Management.
AB - Patients with chest pain who present to emergency departments have a
significantly higher incidence of acute coronary syndrome (ACS) than patients
with chest pain presenting to outpatient settings, so emergency department
clinicians should have a lower threshold for considering ACS as an etiology.
Evaluating patients with suspected ACS in the emergency department involves
obtaining a history, physical examination, electrocardiograms (ECGs), and cardiac
troponin measurements in conjunction with risk calculators. These parameters
cannot be used individually because, for example, a normal ECG result does not
exclude ACS and troponin levels can be elevated in many conditions. All patients
with suspected ACS should receive aspirin, if not contraindicated, as soon as
possible. Those with an ST-segment elevation myocardial infarction (STEMI) or
those without STEMI who are in unstable condition should be triaged to undergo
reperfusion therapy, typically via percutaneous coronary intervention (PCI),
within 120 minutes of first medical contact. If that time limit cannot be met
because the patient must be transferred to a PCI-capable facility, fibrinolytic
therapy should be initiated within 30 minutes of presentation if STEMI is
present. (Fibrinolytic therapy is contraindicated for myocardial infarction
without STEMI.) Patients also should receive nitroglycerin to relieve angina and
beta blockers if not contraindicated.
PMID- 26439395
TI - Acute Coronary Syndrome: Inpatient Management.
AB - The first step in inpatient management of acute coronary syndrome (ACS) is
determining whether the patient has ST-segment elevation myocardial infarction
(STEMI). For STEMI, the initial approach to management is cardiac catheterization
with percutaneous coronary intervention (PCI) to reperfuse the blocked artery;
PCI should take place within 120 minutes of first medical contact. However, if no
contraindications are present, fibrinolytic therapy is preferred if PCI will take
more than 120 minutes. In ACS without STEMI, cardiac catheterization with PCI is
the recommended approach for patients who are unstable, and for stable patients
with high risk assessment scores, diabetes or renal insufficiency, stent
placement within the past 6 months, or prior bypass surgery. Treatment of
patients with ACS who do not meet the previously discussed criteria can be
noninvasive when troponin levels are not elevated, no ST-segment elevations or
depressions are present on electrocardiogram, and risk assessment scores are low.
Assuming no contraindications exist, all patients with or without STEMI should
receive medical therapy that includes nitroglycerin, antiplatelet agents,
anticoagulants, angiotensin-converting enzyme inhibitors or angiotensin II
receptor blockers, aldosterone blockade if left ventricular function is impaired,
beta blockers, and statins.
PMID- 26439396
TI - Acute Coronary Syndrome: Posthospital Outpatient Management.
AB - When providing care for patients who are discharged from the hospital after
experiencing acute coronary syndrome (ACS), several issues should be addressed.
Drug regimens should be reviewed to ensure that patients are taking appropriate
drugs, including antiplatelet agents, angiotensin-converting enzyme
inhibitors/angiotensin II receptor blockers, aldosterone antagonists, beta
blockers/calcium channel blockers, cholesterol-lowering drugs, and nitroglycerin.
The review also should confirm that patients understand when and how to take
their drugs, and that there are no obstacles (eg, cost) that might result in
nonadherence to drug regimens. Lifestyle modifications, including improvements in
diet and exercise regimens, along with participation in a cardiac rehabilitation
program, should be encouraged. Risk factor reduction measures include smoking
cessation for smokers, weight management for patients who are overweight, and
optimal control of blood pressure and blood glucose levels. Appropriate
vaccinations should be administered; influenza and pneumococcal vaccines are
indicated for all patients with ACS in the absence of contraindications. Patients
requiring pain control should avoid use of nonsteroidal anti-inflammatory drugs
because they increase the risk of cardiovascular events; acetaminophen or other
drugs should be used. Finally, depression is common among patients with ACS.
Screening for and management of depression are significant components of care.
PMID- 26439397
TI - Diacylglycerol Guides the Hopping of Clathrin-Coated Pits along Microtubules for
Exo-Endocytosis Coupling.
AB - Many receptor-mediated endocytic processes are mediated by constitutive budding
of clathrin-coated pits (CCPs) at spatially randomized sites before slowly
pinching off from the plasma membrane (60-100 s). In contrast, clathrin-mediated
endocytosis (CME) coupled with regulated exocytosis in excitable cells occurs at
peri-exocytic sites shortly after vesicle fusion (~10 s). The molecular mechanism
underlying this spatiotemporal coupling remains elusive. We show that coupled
endocytosis makes use of pre-formed CCPs, which hop to nascent fusion sites
nearby following vesicle exocytosis. A dynamic cortical microtubular network,
anchored at the cell surface by the cytoplasmic linker-associated protein on
microtubules and the LL5beta/ELKS complex on the plasma membrane, provides the
track for CCP hopping. Local diacylglycerol gradients generated upon exocytosis
guide the direction of hopping. Overall, the CCP-cytoskeleton-lipid interaction
demonstrated here mediates exocytosis-coupled fast recycling of both plasma
membrane and vesicular proteins, and it is required for the sustained exocytosis
during repetitive stimulations.
PMID- 26439398
TI - LRP2 Acts as SHH Clearance Receptor to Protect the Retinal Margin from Mitogenic
Stimuli.
AB - During forebrain development, LRP2 promotes morphogen signaling as an auxiliary
SHH receptor. However, in the developing retina, LRP2 assumes the opposing
function, mediating endocytic clearance of SHH and antagonizing morphogen action.
LRP2-mediated clearance prevents spread of SHH activity from the central retina
into the retinal margin to protect quiescent progenitor cells in this niche from
mitogenic stimuli. Loss of LRP2 in mice increases the sensitivity of the retinal
margin for SHH, causing expansion of the retinal progenitor cell pool and
hyperproliferation of this tissue. Our findings document the ability of LRP2 to
act, in a context-dependent manner, as activator or inhibitor of the SHH pathway.
Our current findings uncovered LRP2 activity as the molecular mechanism imposing
quiescence of the retinal margin in the mammalian eye and suggest SHH-induced
proliferation of the retinal margin as cause of the large eye phenotype observed
in mouse models and patients with LRP2 defects.
PMID- 26439400
TI - SrGAP2-Dependent Integration of Membrane Geometry and Slit-Robo-Repulsive Cues
Regulates Fibroblast Contact Inhibition of Locomotion.
AB - Migrating fibroblasts undergo contact inhibition of locomotion (CIL), a process
that was discovered five decades ago and still is not fully understood at the
molecular level. We identify the Slit2-Robo4-srGAP2 signaling network as a key
regulator of CIL in fibroblasts. CIL involves highly dynamic contact protrusions
with a specialized actin cytoskeleton that stochastically explore cell-cell
overlaps between colliding fibroblasts. A membrane curvature-sensing F-BAR domain
pre-localizes srGAP2 to protruding edges and terminates their extension phase in
response to cell collision. A FRET-based biosensor reveals that Rac1 activity is
focused in a band at the tip of contact protrusions, in contrast to the broad
activation gradient in contact-free protrusions. SrGAP2 specifically controls the
duration of Rac1 activity in contact protrusions, but not in contact-free
protrusions. We propose that srGAP2 integrates cell edge curvature and Slit-Robo
mediated repulsive cues to fine-tune Rac1 activation dynamics in contact
protrusions to spatiotemporally coordinate CIL.
PMID- 26439401
TI - Investigation of field effects in a solid-state nanopore transistor.
AB - In order to calculate ion currents through solid-state nanopore transistors
realistically, we propose a computational model based on the Poisson-Nernst-Plank
equation. In the present model, we determine the surface charge density locally
on the nanopore by imposing consistency between the ion distribution and the
chemical reaction at the surface. The model can consider a non-uniform influence
by the gate voltage on the inner surface of the nanopore membrane, which enables
us to investigate ion currents depending on the gate geometry such as the
thickness and vertical position within the nanopore. We verify the validity of
the model by comparing the pH dependence of simulation results with the extant
experimental results. We also investigate the transistor behaviour depending on
the surface material, pore geometry and gate position. In particular, we propose
an optimized system to enhance the on/off ratio of the nanopore transistor.
PMID- 26439399
TI - Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a
Limb-Genital cis-Regulatory Element in Snakes.
AB - The amniote phallus and limbs differ dramatically in their morphologies but share
patterns of signaling and gene expression in early development. Thus far, the
extent to which genital and limb transcriptional networks also share cis
regulatory elements has remained unexplored. We show that many limb enhancers are
retained in snake genomes, suggesting that these elements may function in non
limb tissues. Consistent with this, our analysis of cis-regulatory activity in
mice and Anolis lizards reveals that patterns of enhancer activity in embryonic
limbs and genitalia overlap heavily. In mice, deletion of HLEB, an enhancer of
Tbx4, produces defects in hindlimbs and genitalia, establishing the importance of
this limb-genital enhancer for development of these different appendages. Further
analyses demonstrate that the HLEB of snakes has lost hindlimb enhancer function
while retaining genital activity. Our findings identify roles for Tbx4 in genital
development and highlight deep similarities in cis-regulatory activity between
limbs and genitalia.
PMID- 26439402
TI - Facile Carbon Fixation to Performic Acids by Water-Sealed Dielectric Barrier
Discharge.
AB - Carbon fixation refers to the conversion of carbon dioxide (CO2) to organic
materials, as commonly performed in nature through photosynthesis by plants and
other autotrophic organisms. The creation of artificial carbon fixation processes
is one of the greatest challenges for chemistry to solve the critical
environmental issue concerning the reduction of CO2 emissions. We have developed
an electricity-driven facile CO2 fixation process that yields performic acid,
HCO2OH, from CO2 and water at neutral pH by dielectric barrier discharge with an
input electric power conversion efficiency of currently 0.2-0.4%. This method
offers a promising future technology for artificial carbon fixation on its own,
and may also be scaled up in combination with e.g., the post-combustion CO2
capture and storage technology.
PMID- 26439404
TI - Decade in review-technology: Technological advances transforming rheumatology.
PMID- 26439403
TI - Molecular investigation of coexistent chronic myeloid leukaemia and peripheral T
cell lymphoma - a case report.
AB - Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm underlain by the
formation of BCR-ABL1 - an aberrant tyrosine kinase - in the leukaemic blasts.
Long-term survival rates in CML prior to the advent of tyrosine kinase inhibitors
(TKIs) were dismal, albeit the incidence of secondary malignancies was higher
than that of age-matched population. Current figures confirm the safety of TKIs
with conflicting data concerning the increased risk of secondary tumours. We
postulate that care has to be taken when distinguishing between coexisting,
secondary-to-treatment and second in sequence, but independent tumourigenic
events, in order to achieve an unbiased picture of the adverse effects of novel
treatments. To illustrate this point, we present a case of a patient in which CML
and peripheral T-cell lymphoma (PTCL) coexisted, although the clinical
presentation of the latter followed the achievement of major molecular response
of CML to TKIs.
PMID- 26439407
TI - Rheumatoid arthritis: C5orf30 regulates severity of tissue destruction in RA.
PMID- 26439405
TI - Genetics of ankylosing spondylitis--insights into pathogenesis.
AB - Ankylosing spondylitis (AS), an immune-mediated arthritis, is the prototypic
member of a group of conditions known as spondyloarthropathies that also includes
reactive arthritis, psoriatic arthritis and enteropathic arthritis. Patients with
these conditions share a clinical predisposition for spinal and pelvic joint
dysfunction, as well as genetic associations, notably with HLA-B(*)27.
Spondyloarthropathies are characterized by histopathological inflammation in
entheses (regions of high mechanical stress where tendons and ligaments insert
into bone) and in the subchondral bone marrow, and by abnormal osteoproliferation
at involved sites. The association of AS with HLA-B(*)27, first described >40
years ago, led to hope that the cause of the disease would be rapidly
established. However, even though many theories have been advanced to explain how
HLA-B(*)27 is involved in AS, no consensus about the answers to this question has
been reached, and no successful treatments have yet been developed that target
HLA-B27 or its functional pathways. Over the past decade, rapid progress has been
made in discovering further genetic associations with AS that have shed new light
on the aetiopathogenesis of the disease. Some of these discoveries have driven
translational ideas, such as the repurposing of therapeutics targeting the
cytokines IL-12 and IL-23 and other factors downstream of this pathway. AS
provides an excellent example of how hypothesis-free research can lead to major
advances in understanding pathogenesis and to the development of innovative
therapeutic strategies.
PMID- 26439406
TI - Strategies for the prevention of knee osteoarthritis.
AB - Osteoarthritis (OA) has been thought of as a disease of cartilage that can be
effectively treated surgically at severe stages with joint arthroplasty. Today,
OA is considered a whole-organ disease that is amenable to prevention and
treatment at early stages. OA develops slowly over 10-15 years, interfering with
activities of daily living and the ability to work. Many patients tolerate pain,
and many health-care providers accept pain and disability as inevitable
corollaries of OA and ageing. Too often, health-care providers passively await
final 'joint death', necessitating knee and hip replacements. Instead, OA should
be viewed as a chronic condition, where prevention and early comprehensive-care
models are the accepted norm, as is the case with other chronic diseases. Joint
injury, obesity and impaired muscle function are modifiable risk factors amenable
to primary and secondary prevention strategies. The strategies that are most
appropriate for each patient should be identified, by selecting interventions to
correct--or at least attenuate--OA risk factors. We must also choose the
interventions that are most likely to be acceptable to patients, to maximize
adherence to--and persistence with--the regimes. Now is the time to begin the era
of personalized prevention for knee OA.
PMID- 26439408
TI - Acute Edema Blisters on a Skin Swelling: An Unusual Manifestation of Hereditary
Angioedema.
PMID- 26439409
TI - Combination of MD Simulations with Two-State Kinetic Rate Modeling Elucidates the
Chain Melting Transition of Phospholipid Bilayers for Different Hydration Levels.
AB - The phase behavior of membrane lipids plays an important role in the formation of
functional domains in biological membranes and crucially affects molecular
transport through lipid layers, for instance, in the skin. We investigate the
thermotropic chain melting transition from the ordered Lbeta phase to the
disordered Lalpha phase in membranes composed of dipalmitoylphosphatidylcholine
(DPPC) by atomistic molecular dynamics simulations in which the membranes are
subject to variable heating rates. We find that the transition is initiated by a
localized nucleus and followed by the propagation of the phase boundary. A two
state kinetic rate model allows characterizing the transition state in terms of
thermodynamic quantities such as transition state enthalpy and entropy. The
extrapolated equilibrium melting temperature increases with reduced membrane
hydration and thus in tendency reproduces the experimentally observed dependence
on dehydrating osmotic stress.
PMID- 26439411
TI - Porous mixed metal oxides: design, formation mechanism, and application in
lithium-ion batteries.
AB - The relentless pursuit of new electrode materials for lithium ion batteries
(LIBs) has been conducted for decades. Structures with either porous or
nanostructure configurations have been confirmed as advantageous candidates for
energy storage/conversion applications. The integration of the two features into
one structure can provide another chance to improve the electroactivities.
Recently, single-phased mixed metal oxides (MMOs) containing different metal
cations, in particular, have confirmed high electrochemical activities because of
their complex chemical composition, interfacial effects, and the synergic effects
of the multiple metal species. In this review, we will focus on recent research
advances of MMOs with porous architectures as anode materials in the matter of
structural arrangement and compositional manipulation. Moreover, the application
of self-supported MMO-based porous structures as LIB anodes is also explained
herein. More importantly, investigations on the synthetic system and formation
mechanism of porous MMOs will be highlighted. Some future trends for the
innovative design of new electrode materials are also discussed in this review.
The challenges and prospects will draw many researchers' attention.
PMID- 26439410
TI - Terahertz-driven linear electron acceleration.
AB - The cost, size and availability of electron accelerators are dominated by the
achievable accelerating gradient. Conventional high-brightness radio-frequency
accelerating structures operate with 30-50 MeV m(-1) gradients. Electron
accelerators driven with optical or infrared sources have demonstrated
accelerating gradients orders of magnitude above that achievable with
conventional radio-frequency structures. However, laser-driven wakefield
accelerators require intense femtosecond sources and direct laser-driven
accelerators suffer from low bunch charge, sub-micron tolerances and sub
femtosecond timing requirements due to the short wavelength of operation. Here we
demonstrate linear acceleration of electrons with keV energy gain using optically
generated terahertz pulses. Terahertz-driven accelerating structures enable high
gradient electron/proton accelerators with simple accelerating structures, high
repetition rates and significant charge per bunch. These ultra-compact terahertz
accelerators with extremely short electron bunches hold great potential to have a
transformative impact for free electron lasers, linear colliders, ultrafast
electron diffraction, X-ray science and medical therapy with X-rays and electron
beams.
PMID- 26439413
TI - Identification and expression analysis of a novel stylicin antimicrobial peptide
from Kuruma shrimp (Marsupenaeus japonicus).
AB - Antimicrobial peptides (AMPs) are important components of the innate immune
system and function as the first line of defense against invading pathogens. In
current study we identified, cloned and characterized a novel stylicin AMP from
Kuruma shrimp Marsupenaeus japonicus (Mj-sty). The full-length cDNA of Mj-sty was
428 bp with an open reading frame of 315 bp that encoded 104 amino acids. The
theoretical molecular mass of mature Mj-sty was 8.693 kDa with an isoelectric
point (pI) of 4.79. A proline-rich N-terminal region and a C-terminal region
contained 13 cysteine residues were identified. Genomic sequence analysis with
respect to its cDNA showed that Mj-sty was organized into two exons interrupted
by one intron. Tissue-specific expression revealed that Mj-sty was mainly
transcribed in gills and hemocytes. Expression of Mj-sty in early developmental
stages demonstrated that Mj-sty mRNA were present from fertilized eggs to post
larvae of 17 days (PL17), and the expression levels showed a significant
variation in different developmental stages. After challenge of white spot
syndrome virus (WSSV), the time-dependent expression pattern of Mj-sty in both
gills and hepatopancrease showed down-regulation at the early hours of infection,
subsequently up-regulation and down-regulation, and then up-regulation at the end
hours to almost the half of the controls. The results indicate that Mj-sty is
potentially involved in the ontogenesis and immune responses against WSSV.
PMID- 26439414
TI - Identification and characterization of the TLR18 gene in grass carp
(Ctenopharyngodon idella).
AB - Toll-like receptors (TLRs) play a critical role in the innate immune system.
Although TLR18 is an important member of this family of receptors in fish, the
role of the tlr18 gene in responses to pathogen infection is still unclear. In
this study, we identified and characterized the grass carp tlr18 gene (gctlr18)
to further clarify the function of TLR18 in teleost fish. Gctlr18 spans over 3600
bp and encodes a polypeptide of 852 amino acids. Analysis of the deduced amino
acid sequence showed that gctlr18 encodes structures typical of the TLR family,
including a signal peptide, seven leucine-rich repeats (LRRs), a transmembrane
region, and a (Toll-interleukin-1 receptor) TIR domain. Quantitative RT-PCR
analysis showed that gctlr18 was constitutively expressed in all investigated
tissues, with abundant expression in spleen, gill, heart, intestine, kidney and
fin and low expression in skin, liver and brain. Following grass carp reovirus
challenge and Aeromonas hydrophila inoculation, gctlr18 transcripts were
upregulated significantly in immune-relevant tissues. Stimulation of
Ctenopharyngodon idella kidney (CIK) cells with purified flagellin from Salmo
typhimurium, lipopolysaccharide and polyinosinic-polycytidylic acid stimulation
in vitro resulted in significantly increased gctlr18 expression, reaching a peak
followed by restoration of normal levels. Overexpression of gctlr18 reduced A.
hydrophila invasion by 83.4%. In CIK cells, gctlr18 induced the expression of
proinflammatory cytokines, including il-8, inf-1 and tnf-alpha. Our results
indicate that gctlr18 plays a key role in innate immune responses in teleost
fish.
PMID- 26439415
TI - The effects of feeding beta-glucan to Pangasianodon hypophthalmus on immune gene
expression and resistance to Edwardsiella ictaluri.
AB - Pangasianodon hypophthalmus (striped catfish) is an important aquaculture species
and intensification of farming has increased disease problems, particularly
Edwardsiella ictaluri. The effects of feeding beta-glucans on immune gene
expression and resistance to E. ictaluri in P. hypophthalmus were explored. Fish
were fed 0.1% fungal-derived beta-glucan or 0.1% commercial yeast-derived beta
glucan or a basal control diet without glucan. After 14 days of feeding, the mRNA
expression of immune genes (transferrin, C-reactive protein, precerebellin-like
protein, Complement C3 and factor B, 2a MHC class II and interleukin-1 beta) in
liver, kidney and spleen were determined. Following this fish from each of the
three diet treatment groups were infected with E. ictaluri and further gene
expression measured 24 h post-infection (h.p.i.), while the remaining fish were
monitored over 2 weeks for mortalities. Cumulative percentage mortality at 14
days post-infection (d.p.i.) was less in beta-glucan fed fish compared to
controls. There was no difference in gene expression between dietary groups after
feeding for 14 days, but there was a clear difference between infected and
uninfected fish at 24 h.p.i., and based on principal component analysis beta
glucans stimulated the overall expression of immune genes in the liver, kidney
and spleen at 24 h.p.i.
PMID- 26439416
TI - Carbohydrate-binding motifs in a novel type lectin from the sea mussel
Crenomytilus grayanus: Homology modeling study and site-specific mutagenesis.
AB - The GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus (CGL)
was shown to represent a novel family of lectins and to be characterized by three
amino acid tandem repeats with high (up to 73%) sequence similarities to each
other. We have used homology modeling approach to predict CGL sugar-binding
sites. In silico analysis of CGL-GalNAc complexes showed that CGL contained three
binding sites, each of which included conserved HPY(K)G motif. In silico
substitutions of histidine, proline and glycine residues by alanine in the
HPY(K)G motifs of the Sites 1-3 was shown to lead to loss of hydrogen bonds
between His and GalNAc and to the increasing the calculated CGL-GalNAc binding
energies. We have obtained recombinant CGL and used site-specific mutagenesis to
experimentally examine the role of HPK(Y)G motifs in hemagglutinating and
carbohydrate binding activities of CGL. Substitutions of histidine, proline and
glycine residues by alanine in the HPYG motif of Site 1 and Site 2 was found to
led to complete loss of CGL hemagglutinating and mucin-binding activities. The
same mutations in HPKG motif of the Site 3 resulted in decreasing the mucin
binding activity in 6-folds in comparison with the wild type lectin. The
mutagenesis and in silico analysis indicates the importance of the all three
HPY(K)G motifs in the carbohydrate-binding and hemagglutinating activities of
CGL.
PMID- 26439418
TI - The open retrograde approach as an alternative for failed percutaneous access for
difficult below the knee chronic total occlusions-A case series.
AB - Retrograde puncture via patent pedal vessels can be attempted in failed antegrade
approach for infrapopliteal long chronic total occlusion. However in cases where
the pedal vessels are unable to be visualized via duplex ultrasonography or
fluoroscopy an open approach offers an additional option to a vascular surgeon
for successful recanalization. Our case report highlights 3 cases where
successful hybrid open retrograde approach was able to achieve recanalization of
long chronic total occlusion. PRESENTATION OF CASES: The three cases in our
series presented with critical limb ischaemia. All three cases had undergone
duplex imaging of the affected arterial system. As the antegrade approach to
cross the lesion failed a retrograde approach was attempted in all 3 cases.
However when the usual modality of retrograde puncture via the use of ultrasound
or fluoroscopy failed we proceeded with an open approach. DISCUSSION: Retrograde
approach usually offers a better chance of successfully crossing a chronic total
occlusion lesion. However puncturing a distal vessel successfully and traversing
a catheter or guidewire across proves to be a challenge. An open approach offers
an additional pathway for puncturing the target vessel when duplex imaging or
fluoroscopic guidance fails. CONCLUSION: Open approach is usually attempted as a
last resort by many endovascular surgeons. However procedural time, contrast and
radiation usage could have been cut short in cases where the distal target
vessels pose a technical challenge for approach via a percutaneous method.
PMID- 26439417
TI - Effects of date palm fruit extracts on skin mucosal immunity, immune related
genes expression and growth performance of common carp (Cyprinus carpio) fry.
AB - The aim of this study was to investigate the effects of date palm fruit extracts
(DPFE) on skin mucosal immunity, immune related genes expression and growth
performance of fry common carp (Cyprinus carpio). One hundred and twenty
specimens (4.06 +/- 0.13 g) were supplied and allocated into six aquaria;
specimens in three aquaria were fed non-supplemented diet (control) while the
fish in the other 3 aquaria were fed with DPFE at 200 ml kg(-1). At the end of
feeding trial (8 weeks) skin mucus immune parameters (total immunoglobulins,
lysozyme, protease and alkaline phosphatase activity) and immune related gene
expression (tumor necrosis factor alpha [tnfa], lysozyme [ly] and interleukin-1
beta, [il1b]) in the head-kidney were studied. The results revealed that feeding
carp fry with 200 ml kg(-1) DPFE remarkably elevated the three skin mucus immune
parameters tested (P < 0.05). However, evaluation of immune related gene
expression demonstrated that the expression of tnfa and il1b was considerably
decreased (P < 0.05) in fish fed DPFE diet, while the expression of ly remained
similar (P > 0.05) compared to control fish (fed control diet). Furthermore,
growth performance parameters were significantly improved in fry fed DPFE (P <
0.05). More studies are needed to understand different aspects of DPFE
administration in fry mucosal immunity.
PMID- 26439419
TI - Scalp actinomycosis presenting as soft tissue tumour: A case report with
literature review.
AB - INTRODUCTION: Actinomycosis is a rare subacute or chronic bacterial infection
caused by Gram positive, anaerobic or microaerophilic bacilli. It is
characterized by suppuration, abscess formation, tissue fibrosis, draining
sinuses & rarely as a soft tissue mass mimicking a tumor. CASE REPORT: A 16 year
old boy sustained a trauma over right forehead & wound after which patient
presented with swelling over right forehead which was excised and was
histopathologically reported as angiomatous lesion. Patient presented with
recurrent swelling with ulceration over the same site. CT scan showed soft tissue
mass with periosteal reaction of right frontal bone. Wide local excision with
removal of periosteum was carried out. Raw area was covered with rotational scalp
flap. Histopathology of the excised specimen showed features of actinomycosis.
DISCUSSION: Cutaneous actinomycosis presenting as pseudocarcinomatous or
sarcomatous mass is rare. Trauma is a common preceding event which was observed
in present case. Histopathological confirmation is mandatory with visualization
of sulfur granules. It is managed by high dose IV antibiotics. Surgical resection
is a useful adjuvant therapy specially in large, disfiguring masses not
responding to medical treatment and where excisional biopsy is helpful in
establishing the diagnosis surgical excision alone is not curative, post
operative long term antibiotics are adjuvant therapy to avoid recurrence.
CONCLUSION: Actinomycosis of scalp skin is a rare entity and tumor like
presentation is still uncommon. Lesions not resolving with routine antibiotics
therapy should be suspected clinically as actinomycosis and treated with high
dose antibiotics as histopathology from small biopsy is unreliable.
PMID- 26439420
TI - Cation Exchange Resins and colonic perforation. What surgeons need to know.
AB - INTRODUCTION: Since 1961 the use of Cation Exchange Resins has been the
mainstream treatment for chronic hyperkalemia. For the past 25 years different
kind of complications derived from its clinical use have been recognized, being
the colonic necrosis the most feared and lethal of all. PRESENTATION OF CASE: We
report a case of a 72-year-old patient with chronic kidney disease, treated with
calcium polystyrene sulfonate for hyperkalemia treatment who presented in the
emergency department with constipation treated with hypertonic cathartics. With
clinical deterioration 48h later progressed with colonic necrosis requiring
urgent laparotomy, sigmoidectomy and open abdomen management with subsequent
rectal stump perforation and dead. The histopathology finding: calcium
polystyrene sulfonate embedded in the mucosa, consistent with the cause of
perforation. DISCUSSION: Lillemoe reported the first case series of five uremic
patients with colonic perforation associated with the use of SPS in sorbitol in
1987 and in 2009 the FDA removed from the market the SPS containing 70% of
sorbitol. The pathophysiologic change of CER goes from mucosal edema, ulcers,
pseudomembranes, and the most severe case transmural necrosis. Up to present day,
some authors have questioned the use of CER in the setting of lowering serum
potassium. Despite its worldwide use in hyperkalemia settings, multiple studies
have not demonstrated a significant potassium excretion by CER. CONCLUSION:
Despite the low incidence of colonic complication and lethal colonic necrosis
associated with the CER clinical use, the general surgeon needs a high index of
suspicion when dealing with patients treated with CER and abdominal pain.
PMID- 26439422
TI - Lactic acid bacterium and yeast microbiotas of sixteen French traditional
sourdoughs.
AB - Sixteen sourdoughs (FS1-FS16) used for the manufacture of traditional French
breads were characterized by strongly acid conditions (median value of pH 3.5).
The concentration of free amino acids (FAA) was highly variable, due to different
proteolytic activity of flour used for back slopping and of dominant
microorganisms. Median value of cell density of lactic acid bacteria (LAB) was
9.2 log CFU/g. The ratio between LAB and yeasts ranged from 10,000:1 to 10:1.
According to the culture-dependent method and 16S metagenetics, Lactobacillus
sanfranciscensis was the dominant species in French sourdoughs. FS5 and FS15,
propagated according to protocols including one back slopping step at 14 degrees
C, were the only exceptions. High positive correlations were found between L.
sanfranciscensis, temperature of back slopping and FAA. The results of this study
highlighted the broad adaptability of L. sanfranciscensis to very acid sourdough.
Besides species frequently encountered (e.g., Lactobacillus
parabrevis/Lactobacillus hammesii, Lactobacillus plantarum and Leuconostoc
mesenteroides), first Lactobacillus xiangfangensis (FS5) and Lactobacillus
diolivorans (FS15) were found in sourdough. As determined by RAPD-PCR analyses,
the sourdough samples showed a different number of strains, ranging from 5 (FS9,
FS11 and FS15) to 12 (FS1 and FS13), meaning a highly variable bacterial
diversity. Cluster analysis showed that different sourdoughs, especially when
propagated in the same bakery, may harbor similar strains. Except for L.
plantarum (FS5) and Ln. mesenteroides (FS3), all the dominant species were
detected by both 16S metagenetics and culture-dependent method. Yeast diversity
was lower than LAB. Except for FS4 (solely dominated by Kazachstania servazzii),
yeast microbiota of French sourdoughs was dominated by Saccharomyces cerevisiae.
Strains isolated in this study could be a useful base for developing new basic
researches on physiology, metabolism, and intraspecific diversity of L.
sanfranciscensis, as well as for standardizing the quality of traditional French
breads.
PMID- 26439421
TI - Meniscectomy versus meniscal repair: 10 years radiological and clinical results
in vertical lesions in stable knee.
AB - INTRODUCTION: Surgical management of meniscal lesion consists of either a
meniscectomy or meniscal repair. Although repair offers immediate recovery after
surgery, it is also associated with higher rates of revision. A meniscectomy, on
the other hand is known to be associated with an early onset of osteoarthritis.
The present study compared clinical and radiological results at 10 years between
meniscectomy and meniscal repair in isolated vertical lesion in an otherwise
stable knee. The hypothesis was that repair shows functional and radiological
benefit over meniscectomy. PATIENTS AND METHOD: A multi-centric retrospective
comparative study of 32 patients (24 male, 8 female). Mean follow-up was 10.6
years (range, 10-13 years). There were 10 meniscal repairs (group R) and 22
meniscectomies (group M), in 17 right and 15 left knees. Mean age at surgery was
33.45+/-12.3 years (range, 9-47 years). There were 28 medial and 4 lateral
meniscal lesions; 26 were in the red-red zone and 6 in red-white zone. RESULTS:
Functional score: KOOS score was significantly higher in group R than M on almost
all parameters: 98+/-4.69 versus 77.38+/-21.97 for symptoms (P=0.0043), 96.89+/
7.20 versus 78.57+/-18.9 for pain (P=0.0052), 99.89+/-0.33 versus 80.88+/-19.6
for daily life activities (P=0.0002), 96.11+/-9.83 versus 54.05+/-32.85 for sport
and leisure (P=0.0005), but 91+/-16.87 versus 68.15+/-37.7 for quality of life
(P=0.1048). Radiology score: in group R, 7 patients had no features of
osteoarthritis, and 2 had grade 1 osteoarthritis. In group M, 5 patients had
grade 1 osteoarthritis, 10 grade 2, 3 grade 3 and 3 grade 4. Mean quantitative
score was 0 (mean, 0.22+/-0.44) in-group R and 2 (mean, 2.19+/-0.98) in group M
(P<0.0001). DISCUSSION: At more than 10year's follow-up, functional scores were
significantly better with meniscal repair than meniscectomy on all parameters of
the KOOS scale except quality of life. Functional and radiological scores
correlated closely. These results show that meniscal repair for vertical lesions
in stable knees protects against osteoarthritis and is therefore strongly
recommended. LEVEL OF EVIDENCE: IV; retrospective study.
PMID- 26439423
TI - Modelling the effect of essential oil of betel leaf (Piper betle L.) on
germination, growth, and apparent lag time of Penicillium expansum on semi
synthetic media.
AB - The current study aimed at characterizing the chemical components of betel leaf
(Piper betle L. var. Tamluk Mitha) essential oil (BLEO) and modelling its effect
on growth of Penicillium expansum on semi-synthetic medium. Gas chromatography
mass spectrophotometry (GC-MS) analysis of BLEO revealed the presence of
different bioactive phenolic compounds in significant amounts. Among 46 different
components identified, chavibetol (22.0%), estragole (15.8%), beta-cubebene
(13.6%), chavicol (11.8%), and caryophyllene (11.3%) were found to be the major
compounds of BLEO. A disc diffusion and disc volatilization method were used to
evaluate antifungal activity of the oil against a selected food spoilage mould.
The logistic model was used to study the kinetics of spore germination.
Prediction and validation of antifungal effect of BLEO was performed on semi
synthetic medium (apple juice agar) using predictive microbiological tools. The
Baranyi and Roberts model was used to estimate maximum growth rate (MUmax in
mm/day) and apparent lag time (lambda in days) of the mould. Secondary modelling
was performed using a re-parameterized Monod-type equation based on cardinal
values to study the effect of different BLEO concentration on estimated growth
parameters. Emax (minimum concentration of oil at which mould growth was
inhibited) and MIC (minimum inhibitory concentration of BLEO at which lag time is
infinite) value of BLEO against P. expansum was estimated to be 0.56 and 0.74
MUl/ml, respectively, which was found to be similar on potato dextrose agar (PDA)
as well as apple juice agar (AJA) medium. The correlation between estimated
growth parameters of the mould on both the media was obtained with satisfactory
statistical indices (R(2) and RMSE). This study revealed inhibitory efficacy of
BLEO on spore germination, mycelial growth and apparent lag time of P. expansum
in a dose-dependent manner. Hence, BLEO has potential to be used as a natural
food preservative.
PMID- 26439424
TI - The association between aerobic fitness and cognitive function in older men
mediated by frontal lateralization.
AB - Previous studies have shown that higher aerobic fitness is related to higher
cognitive function and higher task-related prefrontal activation in older adults.
However, a holistic picture of these factors has yet to be presented. As a
typical age-related change of brain activation, less lateralized activity in the
prefrontal cortex during cognitive tasks has been observed in various
neuroimaging studies. Thus, this study aimed to reveal the relationship between
aerobic fitness, cognitive function, and frontal lateralization. Sixty male older
adults each performed a submaximal incremental exercise test to determine their
oxygen intake (V.O2) at ventilatory threshold (VT) in order to index their
aerobic fitness. They performed a color-word Stroop task while prefrontal
activation was monitored using functional near infrared spectroscopy. As an index
of cognitive function, Stroop interference time was analyzed. Partial correlation
analyses revealed significant correlations among higher VT, shorter Stroop
interference time and greater left-lateralized dorsolateral prefrontal cortex
(DLPFC) activation when adjusting for education. Moreover, mediation analyses
showed that left-lateralized DLPFC activation significantly mediated the
association between VT and Stroop interference time. These results suggest that
higher aerobic fitness is associated with cognitive function via lateralized
frontal activation in older adults.
PMID- 26439426
TI - [First report of invasive fungal disease by Candida fabianii in a non-neonatal
paediatric patient].
AB - BACKGROUND: Invasive fungal diseases have increased in recent years. Candida
species are the most common aetiology. Candida albicans, Candida parapsilosis,
Candida tropicalis, Candida glabrata and Candida krusei are the cause of most of
them. The aim of this work is to describe the first isolation of Candida fabianii
in the blood of a non-neonatal paediatric patient. CASE REPORT: A 2 year-old male
with short bowel syndrome, severe malnutrition, and hypophosphataemic rickets
deficiency was admitted to paediatric intensive care due to a respiratory tract
infection and suspicion of an intestinal pseudo-obstruction. He received several
cycles of broad-spectrum antibiotics for several infections due to Pseudomonas
aeruginosa and Escherichia coli. After the surgical correction of the intestinal
disorder he suffered a new episode of sepsis where yeasts were isolated by
culture. The species identification was performed by means of mass spectrometry
(MALDI-TOF system, Bruker Daltonic). The identity of the isolate was C.fabianii
(anamorph)/Pichia fabianii (teleomorph) with a score of 2.149. Antifungal
treatment with caspofungin was prescribed, with good progress of the patient.
CONCLUSIONS: Molecular techniques are important for the identification of these
species, although mass spectrometry offered a reliable and rapid diagnosis.
Treatment with caspofungin was effective.
PMID- 26439425
TI - Fragile X-associated tremor/ataxia syndrome: An under-recognised cause of tremor
and ataxia.
AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive degenerative
movement disorder resulting from a fragile X "premutation", defined as 55-200 CGG
repeats in the 5'-untranslated region of the FMR1 gene. The FMR1 premutation
occurs in 1/800 males and 1/250 females, with FXTAS affecting 40-45% of male and
8-16% of female premutation carriers over the age of 50. FXTAS typically presents
with kinetic tremor and cerebellar ataxia. FXTAS has a classical imaging profile
which, in concert with clinical manifestations and genetic testing, participates
vitally in its diagnosis. The revised FXTAS diagnostic criteria include two major
radiological features. The "MCP sign", referring to T2 hyperintensity in the
middle cerebellar peduncle, has long been considered the radiological hallmark of
FXTAS. Recently included as a major radiological criterion in the diagnosis of
FXTAS is T2 hyperintensity in the splenium of the corpus callosum. Other imaging
features of FXTAS include T2 hyperintensities in the pons, insula and
periventricular white matter as well as generalised brain and cerebellar atrophy.
FXTAS is an under-recognised and misdiagnosed entity. In patients with
unexplained tremor, ataxia and cognitive decline, the presence of middle
cerebellar peduncle and/or corpus callosum splenium hyperintensity should raise
suspicion of FXTAS. Diagnosis of FXTAS has important implications not only for
the patient but also, through genetic counselling and testing, for future
generations.
PMID- 26439427
TI - Complete genome sequence of Bifidobacterium longum KCTC 12200BP, a probiotic
strain promoting the intestinal health.
AB - Bifidobacteria constitute a major group of beneficial intestinal bacteria, and
are therefore often used to formulate probiotic products in combination with
lactic acid bacteria. The availability of bifidobacterial genome sequences has
broadened our knowledge on health-promoting factors as well as their safety
assessments. Here, we present the complete genome sequence of Bifidobacterium
longum CBT BG7 that consists of a 2.45-Mb chromosome and a plasmid.
PMID- 26439428
TI - Complete genome sequence of Lactobacillus plantarum ZS2058, a probiotic strain
with high conjugated linoleic acid production ability.
AB - Lactobacillus plantarum ZS2058 was isolated from sauerkraut and identified to
synthesize the beneficial metabolite conjugated linoleic acid. The genome
contains a 319,7363-bp chromosome and three plasmids. The sequence will
facilitate identification and characterization of the genetic determinants for
its putative biological benefits.
PMID- 26439429
TI - Complete genome sequence of the probiotic bacterium Bifidobacterium breve KCTC
12201BP isolated from a healthy infant.
AB - We present the completely sequenced genome of Bifidobacterium breve CBT BR3,
which was isolated from the feces of a healthy infant. The 2.43-Mb genome
contains several kinds of genetic factors associated with health promotion of the
human host such as oligosaccharide-degrading genes and vitamin-biosynthetic
genes.
PMID- 26439431
TI - Treatment of dystrophic epidermolysis bullosa with bone marrow non-hematopoeitic
stem cells: a randomized controlled trial.
AB - Patients with dystrophic epidermolysis bullosa (DEB) have mutations in type VII
collagen gene. Type VII collagen is synthesized by keratinocytes and fibroblasts.
Based on the ability of bone marrow non-hematopoeitic stem cells (NHBMSC) to
develop into fibroblasts, we decided to investigate the use of NHBMSC in the
treatment of recessive DEB (RDEB). This study included fourteen patients with
RDEB; the first seven of them were given cyclosporine after the infusion of
NHBMSC. As cyclosporine has been used for the treatment of RDEB we decided not to
use cyclosporine for the second group of seven patients. Skin biopsies from the
lesions were studied by electron microscopy before and after treatment. The
number of new blisters decreased significantly after treatment in both groups (p
= 0.003 and 0.004 respectively) and the rate of healing of new blisters became
significantly faster after treatment in both groups (p < 0.001) with no
significant difference between the two groups. Electron microscopic examination
revealed increased number of anchoring fibrils after treatment in both groups. No
major side effects were reported during the 1-year follow-up period. Our findings
highlight the efficacy as well as the safety of NHBMSC in the treatment of RDEB.
PMID- 26439430
TI - EXPLORING PERSONALITY DIAGNOSIS STABILITY FOLLOWING ACUTE PSYCHOTHERAPY FOR
CHRONIC POSTTRAUMATIC STRESS DISORDER.
AB - BACKGROUND: Axis I comorbidity complicates diagnosing axis II personality
disorders (PDs). PDs might influence Axis I outcome. No research has examined
psychotherapy effects on PDs of treating Axis I comorbidity. Secondary analysis
of a randomized controlled trial examined PD diagnostic stability after brief
psychotherapy of chronic posttraumatic stress disorder (PTSD). METHODS: Patients
with chronic PTSD were randomly assigned to 14 weeks of prolonged exposure,
interpersonal psychotherapy, or relaxation therapy. Assessments included the
Structured Clinical Interview for DSM-IV, Patient Version (SCID-P) and Structured
Clinical Interview for DSM-IV Axis II Disorders (SCID-II) at baseline, week 14,
and for treatment responders (>=30% clinician-administered PTSD scale
improvement, defined a priori) at week 26 follow-up. We hypothesized patients
whose PTSD improved would retain fewer baseline PD diagnoses posttreatment,
particularly with personality traits PTSD mimics, e.g. paranoid and avoidant.
RESULTS: Forty-seven (47%) of 99 SCID-II patients evaluated at baseline received
a SCID-II diagnosis: paranoid (28%), obsessive-compulsive (27%), and avoidant
(23%) PDs were most prevalent. Among 78 patients who repeated SCID-II evaluations
posttreatment, 45% (N = 35) had baseline PD diagnoses, of which 43% (N = 15/35)
lost at week 14. Three (7%) patients without baseline PDs acquired diagnoses at
week 14; 10 others shifted diagnoses. Treatment modality and PTSD response were
unrelated to PD improvement. Of treatment responders reevaluated at follow-up (N
= 44), 56% with any baseline Axis II diagnosis had none at week 26. CONCLUSION:
This first evaluation of Axis I psychotherapy effects on personality disorder
stability found that acutely treating a chronic state decreased apparent trait
across most PDs observed. These exploratory findings suggest personality
diagnoses may have limited prognostic meaning in treating chronic PTSD.
PMID- 26439432
TI - Reply.
PMID- 26439433
TI - Shame, hatred, and pornography: Variations on an aspect of current times.
AB - Drawing on a number of clinical vignettes, the author seeks to highlight the
relations between shame, hatred and pornography in contemporary clinical
practice, and to explore certain metapsychological avenues that can help us
understand how these relations are established.
PMID- 26439434
TI - Photorespiration participates in the assimilation of acetate in Chlorella
sorokiniana under high light.
AB - The development of microalgae on an industrial scale largely depends on the
economic feasibility of mass production. High light induces productive
suspensions during cultivation in a tubular photobioreactor. Herein, we report
that high light, which inhibited the growth of Chlorella sorokiniana under
autotrophic conditions, enhanced the growth of this alga in the presence of
acetate. We compared pigments, proteomics and the metabolic flux ratio in C.
sorokiniana cultivated under high light (HL) and under low light (LL) in the
presence of acetate. Our results showed that high light induced the synthesis of
xanthophyll and suppressed the synthesis of chlorophylls. Acetate in the medium
was exhausted much more rapidly in HL than in LL. The data obtained from LC-MS/MS
indicated that high light enhanced photorespiration, the Calvin cycle and the
glyoxylate cycle of mixotrophic C. sorokiniana. The results of metabolic flux
ratio analysis showed that the majority of the assimilated carbon derived from
supplemented acetate, and photorespiratory glyoxylate could enter the glyoxylate
cycle. Based on these data, we conclude that photorespiration provides glyoxylate
to speed up the glyoxylate cycle, and releases acetate-derived CO2 for the Calvin
cycle. Thus, photorespiration connects the glyoxylate cycle and the Calvin cycle,
and participates in the assimilation of supplemented acetate in C. sorokiniana
under high light.
PMID- 26439435
TI - Functional trait diversity across trophic levels determines herbivore impact on
plant community biomass.
AB - Understanding the consequences of trophic interactions for ecosystem functioning
is challenging, as contrasting effects of species and functional diversity can be
expected across trophic levels. We experimentally manipulated functional identity
and diversity of grassland insect herbivores and tested their impact on plant
community biomass. Herbivore resource acquisition traits, i.e. mandible strength
and the diversity of mandibular traits, had more important effects on plant
biomass than body size. Higher herbivore functional diversity increased overall
impact on plant biomass due to feeding niche complementarity. Higher plant
functional diversity limited biomass pre-emption by herbivores. The functional
diversity within and across trophic levels therefore regulates the impact of
functionally contrasting consumers on primary producers. By experimentally
manipulating the functional diversity across trophic levels, our study
illustrates how trait-based approaches constitute a promising way to tackle
existing links between trophic interactions and ecosystem functioning.
PMID- 26439437
TI - Butyrylcholinesterase Atypical Mutation in a Patient Undergoing Electroconvulsive
Therapy.
PMID- 26439436
TI - Quantification of Adequate Bowel Preparation for Screening or Surveillance
Colonoscopy in Men.
AB - BACKGROUND & AIMS: Bowel preparation is defined as adequate if it is sufficient
for identification of polyps greater than 5 mm. However, adequate preparation has
not been quantified. We performed a prospective observational study to provide an
objective definition of adequate preparation, based on the Boston Bowel Prep
Scale (BBPS, which consists of 0-3 points for each of 3 colon segments). METHODS:
We collected data from 438 men who underwent screening or surveillance
colonoscopies and then repeat colonoscopy examinations within 60 days by a
different blinded endoscopist (1161 colon segments total) at the West Haven
Veterans Affairs Medical Center from January 2014 to February 2015. Missed polyps
were defined as those detected on the second examination of patients with the
best possible bowel preparation (colon segment BBPS score of 3) on the second
examination. The primary outcome was the proportion of colon segments with
adenomas larger than 5 mm that were missed in the first examination. We
postulated that the miss rate was noninferior for segments with BBPS scores of 2
vs those with BBPS scores of 3 (noninferiority margin, <5%). Our secondary
hypotheses were that miss rates were higher in segments with BBPS scores of 1 vs
those with scores of 3 or of 2. RESULTS: The adjusted proportion with missed
adenomas greater than 5 mm was noninferior for segments with BBPS scores of 2
(5.2%) vs those with BBPS scores of 3 (5.6%) (a difference of -0.4%; 95%
confidence interval [CI], -2.9% to 2.2%). Of study subjects, 347 (79.2%) had BBPS
scores of 2 or greater in all segments on the initial examination. A higher
proportion of segments with BBPS scores of 1 had missed adenomas larger than 5 mm
(15.9%) than segments with BBPS scores of 3 (5.6%) (a difference of 10.3%; 95%
CI, 2.7%-17.9%) or 2 (5.2%) (a difference of 10.7%; 95% CI, 3.2%-18.1%).
Screening and surveillance intervals based solely on the findings at the first
examination would have been incorrect for 16.3% of patients with BBPS scores of 3
in all segments, for 15.3% with BBPS scores of 2 or 3 in all segments, and for
43.5% of patients with a BBPS score of 1 in 1 or more segments. CONCLUSIONS:
Patients with BBPS scores of 2 or 3 for all colon segments have adequate bowel
preparation for the detection of adenomas larger than 5 mm and should return for
screening or surveillance colonoscopy at standard guideline-recommended
intervals. Colon segments with a BBPS score of 1 have a significantly higher rate
of missed adenomas larger than 5 mm than segments with scores of 2 or 3. This
finding supports a recommendation for early repeat colonoscopic evaluation in
patients with a BBPS score of 0 or 1 in any colon segment.
PMID- 26439438
TI - Inhaled Loxapine for ECT Pretreatment for Agitation.
PMID- 26439439
TI - A Tool for Assuring Continuity of Care During a Series of ECT Treatments.
PMID- 26439441
TI - Arbitrary and Parallel Nanofabrication of 3D Metal Structures with Polymer Brush
Resists.
AB - 3D polymer brushes are reported for the first time as ideal resists for the
alignment-free nanofabrication of complex 3D metal structures with sub-100 nm
lateral resolution and sub-10 nm vertical resolution. Since 3D polymer brushes
can be serially fabricated in parallel, this method is effective to generate
arbitrary 3D metal structures over a large area at a high throughput.
PMID- 26439440
TI - Genetic and epigenetic transgenerational implications related to omega-3 fatty
acids. Part I: maternal FADS2 genotype and DNA methylation correlate with
polyunsaturated fatty acid status in toddlers: an exploratory analysis.
AB - Polyunsaturated fatty acid metabolism in toddlers is regulated by a complex
network of interacting factors. The contribution of maternal genetic and
epigenetic makeup to this milieu is not well understood. In a cohort of mothers
and toddlers 16 months of age (n = 65 mother-child pairs), we investigated the
association between maternal genetic and epigenetic fatty acid desaturase 2
(FADS2) profiles and toddlers' n-6 and n-3 fatty acid metabolism. FADS2 rs174575
variation and DNA methylation status were interrogated in mothers and toddlers,
as well as food intake and plasma fatty acid concentrations in toddlers. A
multivariate fit model indicated that maternal rs174575 genotype, combined with
DNA methylation, can predict alpha-linolenic acid plasma concentration in all
toddlers and arachidonic acid concentrations in boys. Arachidonic acid intake was
predictive for its plasma concentration in girls, whereas intake of 3 major n-3
species (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) were
predictive for their plasma concentrations in boys. FADS2 genotype and DNA
methylation in toddlers were not related to plasma concentrations or food
intakes, except for CpG8 methylation. Maternal FADS2 methylation was a predictor
for the boys' alpha-linolenic acid intakes. This exploratory study suggests that
maternal FADS2 genetic and epigenetic status could be related to toddlers'
polyunsaturated fatty acid metabolism.
PMID- 26439442
TI - An approach for the improved immobilization of penicillin G acylase onto
macroporous poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) as a
potential industrial biocatalyst.
AB - The use of penicillin G acylase (PGA) covalently linked to insoluble carrier is
expected to produce major advances in pharmaceutical processing industry and the
enzyme stability enhancement is still a significant challenge. The objective of
this study was to improve catalytic performance of the covalently immobilized PGA
on a potential industrial carrier, macroporous poly(glycidyl methacrylate-co
ethylene glycol dimethacrylate) [poly(GMA-co-EGDMA)], by optimizing the
copolymerization process and the enzyme attachment procedure. This synthetic
copolymer could be a very promising alternative for the development of low-cost,
easy-to-prepare, and stable biocatalyst compared to expensive commercially
available epoxy carriers such as Eupergit or Sepabeads. The PGA immobilized on
poly(GMA-co-EGDMA) in the shape of microbeads obtained by suspension
copolymerization appeared to have higher activity yield compared to
copolymerization in a cast. Optimal conditions for the immobilization of PGA on
poly(GMA-co-EGDMA) microbeads were 1 mg/mL of PGA in 0.75 mol/L phosphate buffer
pH 6.0 at 25 degrees C for 24 h, leading to the active biocatalyst with the
specific activity of 252.7 U/g dry beads. Chemical amination of the immobilized
PGA could contribute to the enhanced stability of the biocatalyst by inducing
secondary interactions between the enzyme and the carrier, ensuring multipoint
attachment. The best balance between the activity yield (51.5%), enzyme loading
(25.6 mg/g), and stability (stabilization factor 22.2) was achieved for the
partially modified PGA.
PMID- 26439443
TI - Exercise Pills: At the Starting Line.
AB - Sedentary lifestyles, limited physical exercise, and prolonged inactivity
undoubtedly increase chronic diseases, including obesity, type 2 diabetes, and
cardiovascular diseases. It is widely acknowledged that exercise induces a number
of physiological adaptations that have beneficial effects in the prevention and
treatment of these chronic metabolic diseases. Unfortunately, exercise compliance
is extremely low and often not possible. The development of exercise science and
molecular techniques has increased our understanding of the molecular pathways
responsive to exercise. Knowledge of these molecular targets has led to the
development of chemical interventions that can mimic the beneficial effects of
exercise without requiring actual muscle activity. This review focuses on the
concept of 'exercise pills' and how they mimic the effects produced by physical
exercise including oxidative fiber-type transformation, mitochondrial biogenesis,
increased fat oxidation, angiogenesis, and improvement of exercise capacity. We
also review candidate exercise pills, and contrast the beneficial effects and
molecular mechanisms between physical exercise and exercise pills.
PMID- 26439449
TI - Role of radiation in the treatment of non-metastatic osseous Ewing sarcoma.
AB - INTRODUCTION: Local control, either with surgery, radiation (RT) or both, is
essential in the management of localised Ewing sarcoma; however, the relative
role of RT remains controversial. METHODS: Using the Surveillance, Epidemiology,
and End Results database, 612 patients treated for non-metastatic skeletal Ewing
sarcoma between the years 1988 and 2010 were identified. RESULTS: Median age and
follow-up were 13 years (range: 0-21) and 56 months (range: 0-287), respectively.
Five-year overall survival (OS) for the cohort was 74.4 +/- 2.0%. Patients
received surgery alone (51.3%), RT alone (21.6%) or both (27.1%). Patients with
skeletal Ewing sarcoma had improved OS with surgery alone compared with other
treatments. However, in subset analyses, RT was not inferior to surgery alone for
appendicular (5-year OS: 80.0% vs. 79.3%), non-pelvic (84.3% vs. 79.9%) or
localised disease (confined to cortex or periosteum; 79.7% vs. 80.6%). After
controlling for stage and site, no increase in mortality was observed with RT
versus surgery alone (hazard ratio = 0.77 (95% confidence interval: 0.49-1.19)).
CONCLUSIONS: In regard to survival, RT did not appear to be inferior to surgery
alone for most patients, particularly those with disease at favourable sites
(localised, appendicular, non-pelvic). In select patients with Ewing sarcoma, RT
may be an appropriate strategy for local control that does not necessarily
compromise survival outcomes.
PMID- 26439450
TI - Nonstoichiometric, Protic Azolium Azolate Ionic Liquids Provide Unique
Environments for N-Donor Coordination Chemistry.
AB - Here we demonstrate that neat reactions of amphoteric azoles with more basic
azoles give a family of finely tunable, nonstoichiometric liquids which are
useful for N-donor coordination chemistry. Reacting 4,5-dicyanoimidazole (4,5
DCNIm) with 1-methylimidazole (1-mim) gives new compounds with composition
dependent speciation. Two crystalline compounds, a 1:1 protic salt, [H(1
mim)][4,5-DCNIm], and a 1:2 salt co-crystal, [H(1-mim)][4,5-DCNIm]?4,5-DCNIm,
were isolated and structurally characterized, while differential scanning
calorimetry revealed both suppression of crystallization and the presence of
neutral and anionic species in the melt. Reactions of Cu(NO3 )2 ?2.5 H2 O, CuO,
and ZnO with the neat 2:1 1-mim/4,5-DCNIm melt resulted in the isolation of
entirely N-donor ligated complexes of the formula M(4,5-DCNIm)2 (1-mim)4 (M=Cu,
Zn).
PMID- 26439451
TI - Cardiovascular toxicity after antiangiogenic therapy in persons older than 65
years with advanced renal cell carcinoma.
AB - BACKGROUND: Sorafenib and sunitinib are oral vascular endothelial growth factor
receptor (VEGFR) tyrosine kinase inhibitors (TKIs) approved in 2005 and 2006,
respectively, for the treatment of patients with renal cell carcinoma (RCC). A
population-based, observational cohort study of the cardiovascular risk of VEGFR
TKI therapy in elderly RCC patients was conducted. METHODS: Using the
Surveillance, Epidemiology, and End Results-Medicare database, this study
analyzed patients who were 66 years old or older and were diagnosed with RCC from
2000 to 2009. The incidence of cardiovascular adverse events, including
congestive heart failure and cardiomyopathy (CHF/CM), acute myocardial infarction
(AMI), stroke, and cardiovascular deaths, was examined through December 2010. A
Cox proportional hazards model was created to calculate the hazard ratio (HR),
and adjustments were made for age, sex, comorbidity, and the use of other
systemic therapy. RESULTS: A total of 171 of 670 patients who received sunitinib
or sorafenib had cardiovascular events. The incidence rates for CHF/CM, AMI, and
stroke were 0.87, 0.14, and 0.14 per 1000 person-days, respectively. Sunitinib or
sorafenib use was associated with an increased risk of cardiovascular events (HR,
1.38; 95% confidence interval [CI], 1.02-1.87) and especially stroke (HR, 2.84;
95% CI, 1.52-5.31) in comparison with 788 patients diagnosed with advanced RCC
from 2007 to 2009 who were eligible for Part D but did not receive either agent.
In subgroup analyses, patients who were 66 to 74 years old at diagnosis had the
highest increased risk of stroke associated with the use of either or both drugs.
CONCLUSIONS: Sunitinib and sorafenib might be associated with an increased risk
of cardiovascular events and particularly stroke.
PMID- 26439452
TI - Long-segment percutaneous screw fixation for thoraco-lumbar spine metastases: a
single center's experience.
AB - BACKGROUND: The management of spine metastases is an increasing concern for spine
surgeons. Their treatment is mainly palliative with the goal to preserve or
restore the patients' quality of life. Many minimally invasive techniques have
been introduced with the aim to reduce the morbidity associated with more
traditional open approaches. We aimed to evaluate the efficiency of long segment
percutaneous pedicle screw stabilization for the treatment of instability
associated with symptomatic thoracolumbar spine metastases. METHODS: In this
prospective study, we included all patients who underwent the percutaneous
placement of pedicle screws in our institution between January 2008 and June
2014, for the palliative treatment of a symptomatic thoracolumbar spine
metastasis. All patients had a normal examination. Postoperative radiation
therapy was planned within 2 weeks following the stabilization. A clinical and
radiological follow-up were planned at 3 months, 6 months and 1 year. Pain was
measured using VAS and functional status was assessed using the Frankel Grading
system. CT scan was performed before discharge and at each office evaluation.
RESULTS: Forty-four patients have been included. There were 26 men and 18 women,
with a mean age of 57.3 years (range 36-79 years). The mean operative time was 85
minutes (range 47-124 min), and the estimated blood loss was inferior to 100 mL
in all cases. The mean length of hospital stay was 5.2 days (range 3-18 days).
All patients underwent postoperative radiation therapy within 2 weeks. Pain was
significantly improved from the early postoperative period (P<0.001). Visual
Analogic Scale scores decreased from 6.3 (2-10) to 3.0 (0-6) at discharge. No
patient worsened his neurological condition postoperatively. One patient required
a revision surgery at 3 months due to an important tumor progression at the
treated level. Radiological follow-up demonstrated no case of misplacement,
hardware breakage or loosening. CONCLUSIONS: As the treatment of spine metastases
is largely palliative, minimally invasive techniques should be discussed first to
limit the impact of surgery in critical patients. Long-segment percutaneous screw
fixation followed by early radiation therapy, appears to be a safe and effective
treatment option to ensure solid and durable stability, as well as a good local
tumor control.
PMID- 26439453
TI - Neuroprotective effects of hemicraniectomy in malign middle cerebral artery
infarctions: experimental study.
AB - INTRODUCTION: Despite optimal medical therapy the mortality rate approaches 50%
in MCA infarctions. Although recent studies have been showed life-saving effect
of hemicraniectomy; there are a few data available in regard to neuroprotection
effect of decompressive craniectomy (DC). We induced a malign cerebral ischemia
model by intraluminal permanent middle cerebral artery occlusion (MCAo) in male
rats for defining the neuroprotective effects of early DC on brain-blood barrier
(BBB) molecular changes, infarct size and cerebral edema. MATERIAL-METHOD: 48
male Spraque Dawley rats were allocated to 4 groups; sham (n = 9), control (n =
9), experiment 1 (n = 15), experiment 2 (n = 15). DC was performed by creating a
bone flap, after MCAo at 4th and 24th hours. After 28 hours of survival, all
animals were sacrificed. Infarction volumes were calculated from TTC
(2,3,5,triphenyltetrozolium chloride)- stained brain sections. In all groups,
cerebral edema was quantified as a change in the percentage (%) of brain water
content. Western Blot was used to analyze the expression of tight junction
protein claudin-5 and occludin. RESULTS: Brain water content was calculated
75,18+/-0,75 % in the early DC group and 77,76 +/- 0,71 % in the late DC group.
No significant difference was found between experiment groups (p= .178). In the
early DC group; occludin and claudin-5 were significantly expressed at higher
levels compared to late DC group (for occludin p = .013; for claudin-5 p = .034).
At early DC group (73,38+/-23,11 mm3) the final infarct volumes (in terms of
cubic millimeters; mm3) were significantly smaller than in the late DC group
(377,18+/-39,23 mm3) (p = .013). CONCLUSION: The study results supported the
neuroprotective effects of early DC in malign MCA infarcts.
PMID- 26439454
TI - Developmental venous anomaly as a rare cause of obstructive hydrocephalus:
literature review and a case report.
AB - OBJECT: Developmental venous anomalies (DVA), previously known as cerebral venous
malformations or Venous Angiomas, are common benign entities often incidentally
discovered at MRI examinations. They are non-pathologic variants of normal deep
parenchymal veins that are usually asymptomatic, but they can rarely cause some
complications. In this paper we described a rare case of obstructive
hydrocephalus caused by a DVA located within the cerebral aqueduct and we also
reviewed the previous literature on this topic. CASE REPORT AND METHODS FOR
LITERATURE REVIEW: A 37-year-old man was diagnosed with symptomatic tri
ventricular hydrocephalus that during the last year caused episodes of ictal
headaches accompanied by vertigo, diaphoresis and lipothimic events. The MRI and
the angiography showed the presence of a large collector vein coursing within the
aqueduct, which was part of a complex DVA in the posterior fossa, responsible for
the aqueductal stenosis and obstructive hydrocephalus. The patient was submitted
to endoscopic third ventriculostomy (ETV) and then he had a complete resolution
of symptoms. A literature review was performed through Medline Pubmed
(http://www.ncbi.nlm.nih.gov/pubmed) on papers published in English from 1937 to
2015 with the following key words: DVA, obstructive hydrocephalus, acqueductal
stenosis, venous angioma, venous malformation, medullary malformation. RESULTS:
Including our case, the literature research identified 16 reports in the Medline
database for 18 patients presenting with obstructive hydrocephalus caused by a
DVA including our case. In approximately 60% (10/17) of cases, the stenosis
causing obstructive hydrocephalus was present in the cerebral aqueduct .. The
floor of the IV ventricle and the third ventricle were the second most common
locations and DVAs were identified in 20% of cases (3/17) for each of these
regions. In the remaining case the venous malformation was found in the Foramen
of Monro. Clinical presentation before diagnosis lasted on average 23 months
ranging from 1 month to 7 years. The mean age at diagnosis was 27 (range 3 days-
58 years). The most common presenting symptom was persistent headache,
representing a major complaint in 80% of cases (12/15). In 78% (14/18) of cases
MRI was crucial in the diagnosis. ETV was performed in 47% (8/17) of patients,
whereas no treatment or clinical follow-up was required in 18% (3/17) and VP
Shunt in 12% (2/17) of cases. Instead, VA Shunt, Transcallosal approach and
acqueductal stenting were performed in one patient each, corresponding singularly
to 6% (1/17) of all cases. CONCLUSION: Despite the fact that DVAs are
asymptomatic, they may rarely cause obstructive hydrocephalus because of
impairment in the CSF flow. They should be considered in the differential
diagnosis of any patient presenting with obstructive hydrocephalus. ETV has been
demonstrated as an effective treatment option in the management of obstructive
hydrocephalus due to a DVA.
PMID- 26439455
TI - A Cross-Sectional Study of the Relationship of Physical Activity with Depression
and Cognitive Deficit in Older Adults.
AB - The aim of this study was to examine the association of physical activity with
depression and cognition deficit, separately and combined, in Brazilian older
adults. We analyzed data from 622 older adults. Physical activity was assessed
using the International Physical Activity Questionnaire. Depressive symptoms were
assessed using the Geriatric Depression Scale, while cognitive deficit was
assessed using the Mini-Mental State Examination. Multinomial logistic
regressions were used to assess associations of depression and cognitive deficit
with sociodemographic, health, and behavioral variables. Prevalence of physical
inactivity (< 150 min of moderate-to-vigorous physical activity/ week),
depression, and cognitive deficit were 35.7%, 37.4%, and 16.7%. Physical
inactivity was associated with depression (OR: 1.83, 95% CI: 1.14-2.94) and with
depression and cognitive deficit combined (OR: 4.23, 95% CI: 2.01-8.91).
Physically inactive participants were also more likely to present limitations in
orientation and language functions. Physical inactivity was associated with
depression and also with depression and cognitive deficit combined in older
adults.
PMID- 26439456
TI - Modeling the Assembly of Polymer-Grafted Nanoparticles at Oil-Water Interfaces.
AB - Using dissipative particle dynamics (DPD), I model the interfacial adsorption and
self-assembly of polymer-grafted nanoparticles at a planar oil-water interface.
The amphiphilic core-shell nanoparticles irreversibly adsorb to the interface and
create a monolayer covering the interface. The polymer chains of the adsorbed
nanoparticles are significantly deformed by surface tension to conform to the
interface. I quantitatively characterize the properties of the particle-laden
interface and the structure of the monolayer in detail at different surface
coverages. I observe that the monolayer of particles grafted with long polymer
chains undergoes an intriguing liquid-crystalline-amorphous phase transition in
which the relationship between the monolayer structure and the surface
tension/pressure of the interface is elucidated. Moreover, my results indicate
that the amorphous state at high surface coverage is induced by the anisotropic
distribution of the randomly grafted chains on each particle core, which leads to
noncircular in-plane morphology formed under excluded volume effects. These
studies provide a fundamental understanding of the interfacial behavior of
polymer-grafted nanoparticles for achieving complete control of the adsorption
and subsequent self-assembly.
PMID- 26439458
TI - The tumor microenvironment: the connective tissue/tumor cell/host organ system
that modulates tumor progression.
PMID- 26439457
TI - Cysteine as a Monothiol Reducing Agent to Prevent Copper-Mediated Oxidation of
Interferon Beta During PEGylation by CuAAC.
AB - Bioconjugation by copper-catalyzed azide-alkyne cycloaddition (CuAAC) provides a
powerful means to produce site-specifically modified proteins. However, the use
of a copper catalyst brings about the possible generation of reactive oxygen
species that could cause degradation of vulnerable amino acid residues. We
investigated whether PEGylation by CuAAC caused any modifications to the
therapeutic protein interferon beta-1b, which was produced via global amino acid
substitution with azidohomo-alanine at the N-terminus and contains no methionine
residues. Using previously reported reaction conditions, LC-MS peptide mapping
detected +32 Da and +48 Da oxidation modifications of tryptic peptides 28-33
(LEYCLK) and 137-147 (EYSHCAWTIVR) in the protein post-PEGylation. The oxidative
degradation increased with reaction time, whereas reducing the copper
concentration slowed the PEGylation rate as well as the oxidation rate. Replacing
dithiothreitol (DTT) with any of five different monothiol reducing agents in
anaerobic conditions allowed efficient PEGylation in 2-4 h and abrogated
oxidative degradation. Free cysteine provided reproducible reaction results as a
reducing agent in this system and has been successfully applied to other protein
conjugations. Monothiol reducing agents, such as cysteine, may be useful tools as
protective reducing agents for CuAAC in some bioconjugation systems.
PMID- 26439459
TI - Developing hospital accreditation standards in Uganda.
AB - BACKGROUND: Whereas accreditation is widely used as a tool to improve quality of
healthcare in the developed world, it is a concept not well adapted in most
developing countries for a host of reasons, including insufficient incentives,
insufficient training and a shortage of human and material resources. The purpose
of this paper is to describe refining use and outcomes of a self-assessment
hospital accreditation tool developed for a resource-limited context. METHODS: We
invited 60 stakeholders to review a set of standards (from which a self
assessment tool was developed), and subsequently refined them to include 485
standards in 7 domains. We then invited 60 hospitals to test them. A study team
traveled to each of the 40 hospitals that agreed to participate providing
training and debrief the self-assessment. The study was completed in 8 weeks.
RESULTS: Hospital self-assessments revealed hospitals were remarkably open to
frank rating of their performance and willing to rank all 485 measures. Good
performance was measured in outreach programs, availability of some types of
equipment and running water, 24-h staff calls systems, clinical guidelines and
waste segregation. Poor performance was measured in care for the vulnerable,
staff living quarters, physician performance reviews, patient satisfaction
surveys and sterilizing equipment. CONCLUSION: We have demonstrated the
feasibility of a self-assessment approach to hospital standards in low-income
country setting. This low-cost approach may be used as a good precursor to
establishing a national accreditation body, as indicated by the Ministry's
efforts to take the next steps. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26439467
TI - Anisotropic Effective Mass, Optical Property, and Enhanced Band Gap in
BN/Phosphorene/BN Heterostructures.
AB - Phosphorene is receiving great research interests because of its peculiar
physical properties. Nonetheless, the phosphorus has a trouble of degradation due
to oxidation. Hereby, we propose that the electrical and optical anisotropic
properties can be preserved by encapsulating into hexagonal boron nitride (h-BN).
We found that the h-BN contributed to enhancing the band gap of the phosphorene
layer. Comparing the band gap of the pristine phosphorene layer, the band gap of
the phosphorene/BN(1ML) system was enhanced by 0.15 eV. It was further enhanced
by 0.31 eV in the BN(1ML)/phosphorene/BN(1ML) trilayer structure. However, the
band gap was not further enhanced when we increased the thickness of the h-BN
layers even up to 4 MLs. Interestingly, the anisotropic effective mass and
optical property were still preserved in BN/phosphorene/BN heterostructures.
Overall, we predict that the capping of phosphorene by the h-BN layers can be an
excellent solution to protect the intrinsic properties of the phosphorene.
PMID- 26439460
TI - Room for one more? A review of the literature on 'inappropriate' admissions to
hospital for older people in the English NHS.
AB - This paper reports the findings of a review of the literature on emergency
admissions to hospital for older people in the UK, undertaken between May and
June 2014 at the Health Services Management Centre, University of Birmingham.
This review sought to explore: the rate of in/appropriate emergency admissions of
older people in the UK; the way this is defined in the literature; solutions
proposed to reduce the rate of inappropriate admissions; and the methodological
issues which particular definitions of 'inappropriateness' raise. The extent to
which a patient perspective is included in these definitions of inappropriateness
was also noted, given patient involvement is such a key policy priority in other
areas of health policy. Despite long-standing policy debates, relatively little
research has been published on formal rates of 'inappropriate' emergency hospital
admissions for older people in the UK NHS in recent years. What has been produced
indicates varying rates of in/appropriateness, inconsistent ways of defining
appropriateness and a lack of focus on the possible solutions to address the
problem. Significantly, patient perspectives are lacking, and we would suggest
that this is a key factor in fully understanding how to prevent avoidable
admissions. With an ageing population, significant financial challenges and a
potentially fragmented health and social care system, the issue of the
appropriateness of emergency admission is a pressing one which requires further
research, greater focus on the experiences of older people and their families,
and more nuanced contextual and evidence-based responses.
PMID- 26439468
TI - Approach to Modeling, Therapy Evaluation, Drug Selection, and Biomarker
Assessments for a Multicenter Pre-Clinical Drug Screening Consortium for Acute
Therapies in Severe Traumatic Brain Injury: Operation Brain Trauma Therapy.
AB - Traumatic brain injury (TBI) was the signature injury in both the Iraq and Afghan
wars and the magnitude of its importance in the civilian setting is finally being
recognized. Given the scope of the problem, new therapies are needed across the
continuum of care. Few therapies have been shown to be successful. In severe TBI,
current guidelines-based acute therapies are focused on the reduction of
intracranial hypertension and optimization of cerebral perfusion. One factor
considered important to the failure of drug development and translation in TBI
relates to the recognition that TBI is extremely heterogeneous and presents with
multiple phenotypes even within the category of severe injury. To address this
possibility and attempt to bring the most promising therapies to clinical trials,
we developed Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical
drug screening consortium for acute therapies in severe TBI. OBTT was developed
to include a spectrum of established TBI models at experienced centers and assess
the effect of promising therapies on both conventional outcomes and serum
biomarker levels. In this review, we outline the approach to TBI modeling,
evaluation of therapies, drug selection, and biomarker assessments for OBTT, and
provide a framework for reports in this issue on the first five therapies
evaluated by the consortium.
PMID- 26439469
TI - Atmospheric Chemistry of (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3.
AB - Smog chambers with in situ FTIR detection were used to measure rate coefficients
in 700 Torr of air and 296 +/- 2 K of: k(Cl+(CF3)2CHOCH3) = (5.41 +/- 1.63) * 10(
12), k(Cl+(CF3)2CHOCHO) = (9.44 +/- 1.81) * 10(-15), k(Cl+CF3C(O)OCH3) = (6.28 +/
0.98) * 10(-14), k(OH+(CF3)2CHOCH3) = (1.86 +/- 0.41) * 10(-13), and
k(OH+(CF3)2CHOCHO) = (2.08 +/- 0.63) * 10(-14) cm(3) molecule(-1) s(-1). The Cl
atom initiated oxidation of (CF3)2CHOCH3 gives (CF3)2CHOCHO in a yield
indistinguishable from 100%. The OH radical initiated oxidation of (CF3)2CHOCH3
gives the following products (molar yields): (CF3)2CHOCHO (76 +/- 8)%,
CF3C(O)OCH3 (16 +/- 2)%, CF3C(O)CF3 (4 +/- 1)%, and C(O)F2 (45 +/- 5)%. The
primary oxidation product (CF3)2CHOCHO reacts with Cl atoms to give secondary
products (molar yields): CF3C(O)CF3 (67 +/- 7)%, CF3C(O)OCHO (28 +/- 3)%, and
C(O)F2 (118 +/- 12)%. CF3C(O)OCH3 reacts with Cl atoms to give: CF3C(O)OCHO (80
+/- 8)% and C(O)F2 (6 +/- 1)%. Atmospheric lifetimes of (CF3)2CHOCH3,
(CF3)2CHOCHO, and CF3C(O)OCH3 were estimated to be 62 days, 1.5 years, and 220
days, respectively. The 100-year global warming potentials (GWPs) for
(CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3 are estimated to be 6, 121, and 46,
respectively. A comprehensive description of the atmospheric fate of (CF3)2CHOCH3
is presented.
PMID- 26439470
TI - Direct and indirect effects of the 13-valent pneumococcal conjugate vaccine
administered to infants and young children.
AB - This paper analyzes the most recent reports regarding the direct and indirect
effects of the 13-valent pneumococcal conjugate vaccine (PCV13) when administered
to infants and young children. PCV13 extends the protective effects reported for
the 7-valent pneumococcal conjugate vaccine (PCV7). A further reduction in the
incidence of invasive pneumococcal disease, community-acquired pneumonia, acute
otitis media, rhinosinusitis and carriage of PCV13 serotypes in vaccinated and
unvaccinated subjects was found with PCV13 compared with PCV7. However, further
studies are required to establish the effectiveness of PCV13 against serotypes 1,
5 and 3, the role of cross-protective antibodies evoked by serotype 6A on
serotype 6C and the importance of the serotype replacement phenomenon following
the extension of PCV13 use.
PMID- 26439471
TI - Genetic polymorphisms of matrix metalloproteinases and protein levels in chronic
obstructive pulmonary disease in a Mexican population.
AB - AIM: To evaluate association of single nucleotide polymorphisms (SNPs) in the
MMP1, MMP2, MMP9 and MMP12 genes and serum MMP-2 and MMP-9 levels in smoking
chronic obstructive pulmonary disease (COPD) patients. MATERIALS & METHODS:
Genotyping using real-time PCR in 330 smokers with COPD (COPD), 658 smokers
without COPD (SNC) and 150 nonsmokers (NCNS), the analysis of samples used was
chi(2) test. Using ELISA, the proteins were evaluated. Multiple comparisons were
made by ANOVA. RESULTS: rs243864 (OR: 7.44; 95% CI: 3.62-15.26) and rs11646643
(OR: 1.58; 95% CI: 1.07-2.34) of the MMP-2 gene and rs3918253 (OR: 1.72; 95% CI:
1.08-2.71) of the MMP-9 gene, were associated with the risk of COPD. Serum MMP-2
level in the COPD group was lower compared with SNC (p < 0.05). Serum MMP-9 level
was elevated in the COPD group compared with SNC (p < 0.05). CONCLUSION:
Polymorphisms in MMP2 and MMP9 but not in MMP1 and MMP12 are associated with the
risk of COPD in the Mexican mestizo population.
PMID- 26439472
TI - Synthesis of Polyheteroaromatic Compounds via Rhodium-Catalyzed Multiple C-H Bond
Activation and Oxidative Annulation.
AB - Polyheteroaromatic compounds are potential optoelectronic conjugated materials
due to their electro- and photochemical properties. Transition-metal-catalyzed
multiple C-H activation and sequential oxidative annulation allows rapidly
assembling of those compounds from readily available starting materials. A
rhodium-catalyzed cascade oxidative annulation of beta-enamino esters or 4
aminocoumarins with internal alkynes is described to access those compounds,
featuring multiple C-H/N-H bond cleavages and sequential C-C/C-N bond formations
in one pot.
PMID- 26439473
TI - Comparative effects of group metacognitive therapy versus behavioural activation
in moderately depressed students.
AB - BACKGROUND: The high incidence and prevalence rates of depression among students
identify them as a vulnerable population and make the case for the development of
cost-effective treatments. AIMS: We aimed to examine the comparative effects of
brief group metacognitive therapy (MCT) versus behavioural activation (BA)
treatments for depression, anxiety, and emotion regulation in university
students. METHOD: All participants (25 women, 16 men; age range: 18-30 years)
fulfilled criteria for major depression and were randomly assigned to MCT (n =
15), BA (n = 15), or a wait-list control group (n = 15). The treatment groups
received 8 weekly MCT or BA sessions. Scores on the Beck Depression Inventory,
Beck Anxiety Inventory, and Cognitive Emotion Regulation Questionnaire were used
as outcome measures. RESULTS: This pilot study showed that both treatments were
equally effective for depressive and anxiety symptoms. However, therapeutic
techniques differed with regards to their effects on specific facets of emotion
regulation, such as Positive Reappraisal and Catastrophizing, with MCT being more
effective compared to BA. BA also showed a stronger relapse at follow-up with
regards to Acceptance and Refocus on Planning. CONCLUSIONS: Results suggest that
groups MCT and BA may be implemented as cost-effective treatments for students
with moderate depression.
PMID- 26439474
TI - Rapid analysis of diclofenac in freshwater and wastewater by a monoclonal
antibody-based highly sensitive ELISA.
AB - The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is found
worldwide in the aqueous environment. Therefore, it has raised increased public
concern on potential long-term impact on human health and wildlife. The
importance of DCF has been emphasized by the European Union recently by including
this pharmaceutical in the first watch list of priority hazardous substances in
order to gather Union-wide monitoring data. Rapid and cheap methods of analysis
are therefore required for fresh and wastewater monitoring with high sample load.
Here, for the first time, well-characterized monoclonal antibodies (mAbs) against
DCF were generated and a highly sensitive ELISA developed. The best antibody (mAb
12G5) is highly affine (KD = 1.5 * 10(-10) M), stable to potential matrix
interferences such as pH value (pH range 5.2-9.2), calcium ion concentration (up
to 75 mg/L), and humic acid content (up to 20 mg/L). The limit of detection (LOD,
S/N = 3) and IC50 of the ELISA calibration curve were 7.8 and 44 ng/L,
respectively. The working range was defined between 11 and 180 ng/L. On average,
about 10 % cross-reactivity (CR) was found for DCF metabolites 5-OH-DCF, 4'-OH
DCF, and DCF-acyl glucuronide, but other structurally related NSAIDs showed
binding <1 % compared to the parent compound. While DCF concentrations at the low
ppt range were measured in river and lake water, higher values of 2.9 and 2.1
MUg/L were found in wastewater influents and effluents, respectively. These
results could be confirmed by solid phase extraction combined with LC-MS.
PMID- 26439476
TI - Correction to "Oxidatively Initiated NHC-Catalyzed Enantioselective Synthesis of
3,4-Disubstituted Cyclopentanones from Enals".
PMID- 26439475
TI - Citrate salts for preventing and treating calcium containing kidney stones in
adults.
AB - BACKGROUND: Kidney stones affect people worldwide and have a high rate of
recurrence even with treatment. Recurrences are particularly prevalent in people
with low urinary citrate levels. These people have a higher incidence of calcium
phosphate and calcium oxalate stones. Oral citrate therapy increases the urinary
citrate levels, which in turn binds with calcium and inhibits the crystallisation
thus reduces stone formation. Despite the widespread use of oral citrate therapy
for prevention and treatment of calcium oxalate stones, the evidence to support
its clinical efficacy remains uncertain. OBJECTIVES: The objective of this review
was to determine the efficacy and adverse events associated with citrate salts
for the treatment and prevention of calcium containing kidney stones. SEARCH
METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to
29 July 2015 through contact with the Trials' Search Co-ordinator using search
terms relevant to this review. SELECTION CRITERIA: We included randomised
controlled trials (RCTs) that assessed the efficacy and adverse events associated
with citrate salts for the treatment and prevention of calcium containing kidney
stones in adults treated for a minimum of six months. DATA COLLECTION AND
ANALYSIS: Two authors assessed studies for inclusion in this review. Data were
extracted according to predetermined criteria. 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: We included
seven studies that included a total of 477 participants, most of whom had oxalate
stones. Of these, three studies (247 participants) compared potassium citrate
with placebo or no intervention; three (166 participants) compared potassium
sodium citrate with no intervention; and one (64 participants) compared potassium
magnesium citrate with placebo. Overall, quality of the reporting of the included
studies was considered moderate to poor, and there was a high risk of attrition
bias in two studies.Compared with placebo or no intervention, citrate therapy
significantly reduced the stone size (4 studies, 160 participants: RR 2.35, 95%
CI 1.36 to 4.05). New stone formation was significantly lower with citrate
therapy compared to control (7 studies, 324 participants: RR 0.26, 95% CI 0.10 to
0.68). The beneficial effect on stone size stability was also evident (4 studies,
160 participants: RR 1.97, 95% CI 1.19 to 3.26). Adverse events were reported in
four studies, with the main side effects being upper gastrointestinal disturbance
and one patient reported a rash. There were more gastrointestinal adverse events
in the citrate group; however this was not significant (4 studies, 271
participants: RR 2.55, 95% CI 0.71 to 9.16). There were significantly more
dropouts due to adverse events with citrate therapy compared to control (4
studies, 271 participants: RR 4.45, 95% CI 1.28 to 15.50). The need for
retreatment was significantly less with citrate therapy compared to control (2
studies, 157 participants: RR 0.22, 95% CI 0.06 to 0.89). AUTHORS' CONCLUSIONS:
Citrate salts prevent new stone formation and reduce further stone growth in
patients with residual stones that predominantly contain oxalate. The quality of
reported literature remains moderate to poor; hence a well-designed statistically
powered multi-centre RCT is needed in order to answer relevant questions
concerning the efficacy of citrate salts.
PMID- 26439477
TI - Protective activity of crocin against indomethacin-induced gastric lesions in
rats.
AB - The present study was designed to elucidate the mechanism(s) of the gastro
protective effect of crocin against indomethacin-induced gastric lesions. Crocin
or pantoprazole was administered to rats 30 min before indomethacin. Five hours
later, the animals were killed and their stomachs were removed and examined
macroscopically. Samples of gastric mucosa were collected for microscopic
evaluation, mRNA expression of caspase-3, inducible nitric oxide synthase (iNOS)
and cyclooxygenase (COX)-2 was quantified by RT-PCR, and protein levels of COX-1,
COX-2, iNOS and caspase-3 were assessed by Western blotting. The pH, volume of
gastric effluent and antioxidant activity were measured in 5 separate groups of
rats following pylorus ligation. Indomethacin induced significant increases in
mRNA and protein expression of iNOS and caspase-3 and increased MDA levels, and
reduced the pH of the gastric effluent and protein and mRNA expression of COX-2
and protein expression of COX-1 and mucus content associated with gastric
ulceration. Crocin and pantoprazole significantly inhibited mRNA and protein
expression of iNOS, caspase-3 and MDA, and reduced mucus content induced by
indomethacin. However, unlike pantoprazole, crocin failed to increase COX-1 and
pH, but had variable increasing effects on mRNA and protein expression of COX-2.
Macroscopic and microscopic observations showed that mucosal erosions induced by
indomethacin were significantly inhibited by pantoprazole and crocin. These
findings suggest that crocin exerts its gastro-protective effects mainly by
inhibition of MDA, reduction in iNOS and caspase-3, and inhibition of the
reduction in mucus content induced by indomethacin. Crocin is a novel agent that
has potential in the prevention of ulceration induced by NSAIDs.
PMID- 26439478
TI - LC-MS-based quantification method for Achyranthes root saponins.
AB - A liquid chromatography mass spectrometry (LC-MS) method was developed for
simultaneous quantitative analysis of Achyranthes root saponins:
chikusetsusaponins IVa (1) and V (2), achyranthosides B (3), C (4), D (5), E (6),
and G (7), sulfachyranthosides B (8) and D (9), and betavulgarosides II (10) and
IV (11). Satisfactory separation of the saponins was achieved with the use of a
volatile ion-pair reagent (dihexyl ammonium acetate) on a phenyl-hexylated silica
gel column, and the amounts of saponins extracted under three different
conditions were determined. When Achyranthes root was extracted with water at
room temperature, achyranthosides B (3) and D (5) were the major saponins, and
smaller amounts of other saponins (4, 6-11) were present. However, the amounts of
chikusetsusaponins (1 and 2) were negligible. Under the condition to make a
standard decoction of a Kampo formula, the major saponins were achyranthosides B
(3), C (4), and D (5), and small amounts of chikusetsusaponins IVa (1) and V (2)
appeared, whereas prolonged heating largely increased the amounts of
chikusetsusaponins. This method can be used for quality control of Achyranthes
root.
PMID- 26439480
TI - Emotion Perception or Social Cognitive Complexity: What Drives Face Processing
Deficits in Autism Spectrum Disorder?
AB - Some, but not all, relevant studies have revealed face processing deficits among
those with autism spectrum disorder (ASD). In particular, deficits are revealed
in face processing tasks that involve emotion perception. The current study
examined whether either deficits in processing emotional expression or deficits
in processing social cognitive complexity drive face processing deficits in ASD.
We tested adults with and without ASD on a battery of face processing tasks that
varied with respect to emotional expression processing and social cognitive
complexity. Results revealed significant group differences on tasks involving
emotional expression processing, but typical performance on a non-emotional but
socially complex task. These results support an emotion processing rather than a
social complexity explanation for face processing deficits in ASD.
PMID- 26439479
TI - Antiviral effects of Yinhuapinggan granule against influenza virus infection in
the ICR mice model.
AB - Yinhuapinggan granule (YHPG), a Chinese medicine granule based on Ma-Huang-Tang
(Ephedra Decoction) and the clinical experience of Professor Wan Haitong, is used
in traditional Chinese medicine (TCM) for the treatment of colds, influenza,
fever, inflammation and cough. This study investigated the antiviral effects of
YHPG on the production of inflammatory cytokines in influenza virus (IFV)
infected mice and evaluated the effect of YHPG on the expression of NF-kappaB p65
and the level of key signaling molecules in the TLR4 signaling pathway. ICR mice
were orally administrated YHPG at doses of 7.5, 15 and 30 g kg(-1) day(-1) for 2
or 6 days after IFV infection. On days 3 and 7 after infection, YHPG (15 g/kg and
30 g/kg) significantly increased levels of interleukin (IL)-2 and interferon
gamma and decreased levels of IL-4, IL-5 and tumor necrosis factor (TNF) in serum
compared with the IFV control group. Furthermore, the expression of TLR4, MyD88,
TRAF6 and NF-kappaB p65 at the mRNA and protein level was significantly lower in
the YHPG (15 and 30 g/kg) treatment groups than in the IFV control group. These
results suggest that YHPG has antiviral effects in IFV-infected mice, which is
associated with the inhibition of the TLR4-MyD88-TRAF6 signaling pathway and the
expression of NF-kappaB p65.
PMID- 26439482
TI - Celiac disease and dental enamel defects: what is the link?
PMID- 26439481
TI - Are Non-intellectually Disabled Black Youth with ASD Less Impaired on Parent
Report than Their White Peers?
AB - There is a lack of research examining differences in functioning in autism
spectrum disorder (ASD) across ethnicity, particularly among those without
intellectual disability (ID). This study investigated ethnic differences in
parent-reported impairment in executive function, adaptive behavior, and social
emotional functioning. White and Black youth (n = 64; ages 6-17) with ASD without
ID were compared on each of these domains. Black youth had significantly lower
levels of impairment on all three domains. Findings may reflect better daily
functioning among Black youth with ASD and/or cultural differences in parent
response to questionnaires. Regardless, these findings raise concern about the
sensitivity of commonly used measures for Black children with ASD and the impact
of culture on daily functioning and symptom manifestation.
PMID- 26439483
TI - A case of a strangulated umbilical hernia causing gangrenous appendicitis.
PMID- 26439484
TI - A 10-year history of perinatal care at the Brockington Mother and Baby Unit
Stafford.
AB - Perinatal mother and baby units are an essential service for women suffering from
perinatal mental illness by allowing the baby to stay with the mother whilst
receiving inpatient mental health care. Such units enable the mother to develop a
relationship with her baby in a safe and supportive environment whilst caring for
her mental health needs and allow her to gain confidence in her role as a mother.
This article presents the development of the Brockington Mother and Baby unit and
its progressive advancement towards an exemplary service for women suffering from
perinatal mental illness. The Brockington Mother and Baby unit (MBU) at South
Staffordshire and Shropshire Healthcare Foundation Trust (SSSFT) is celebrating
its 10th anniversary and is one of six MBUs accredited as excellent by the Royal
College of Psychiatry (RCPsych). The unit is a member of the Royal College of
Psychiatrists' Quality Care Network and thereby adheres to their national
standard of care. This article describes the journey from a single lone worker in
perinatal mental health to an exemplary service caring for women with perinatal
mental illness during the first 12 months following the birth of their child.
PMID- 26439485
TI - Cerebellar Contribution to Pattern Separation of Human Hippocampal Memory
Circuits.
AB - The cerebellum is a crucial structure for cognitive function as well as motor
control. Benign brain tumors such as schwannomas, meningiomas, and epidermoids
tend to occur in the cerebellopontine angle cisterns and may cause compression of
the posterior lateral cerebellum near the superior posterior fissure, where the
eloquent area for cognitive function was recently identified. The present study
examined cognitive impairment in patients with benign cerebellar tumors before
and after surgical intervention in order to clarify the functional implications
of this region in humans. Patients with cerebellar tumors showed deficits in
psychomotor speed and working memory compared with healthy controls. Moreover,
these impairments were more pronounced in patients with right cerebellar tumors.
Functional magnetic resonance imaging during performance of a lure task also
demonstrated that cerebellar tumors affected pattern separation or the ability to
distinguish similar experiences of episodic memory or events with discrete, non
overlapping representations, which is one of the important cognitive functions
related to the hippocampus. The present findings indicate that compression of the
human posterior lateral cerebellum affects hippocampal memory function.
PMID- 26439487
TI - Cytotoxicity of alkaloids isolated from Argemone mexicana on SW480 human colon
cancer cell line.
AB - CONTEXT: Argemone mexicana Linn. (Papaveraceae) has been used as traditional
medicine in India and Taiwan for the treatment of skin diseases, inflammations,
bilious, fever, etc. Some alkaloids of A. mexicana have been screened for their
cytotoxicity on different cancer cell lines. OBJECTIVE: The study investigates
potential cytotoxic effects of alkaloids isolated from aerial part of A. mexicana
on SW480 human colon cancer cell line. MATERIALS AND METHODS: Six alkaloids, 13
oxoprotopine, protomexicine, 8-methoxydihydrosanguinarine, dehydrocorydalmine,
jatrorrhizine, and 8-oxyberberine were isolated from the methanol extract of A.
mexicana. Cytotoxicity of these alkaloids was studied on SW480 human colon cancer
cell line at 1, 25, 50, 75, 100, 125, 150, and 200 ug/mL for 24 and 48 h. Cells
were seeded in a 96-well micro-plate at a concentration of 2 * 10(4) cells per
well and MTS assay was performed to assess cytotoxicity in terms of cell
viability. RESULTS: At 200 ug/mL, protomexicine and 13-oxoprotopine showed mild
cytotoxicity (~24-28%) whereas dehydrocorydalmine exhibited moderate cytotoxicity
(~48%). 8-Oxyberberine was mildly cytotoxic (~27%) at 24 h but was more potent
(~76%) at 48 h. Jatrorrhizine and 8-methoxydihydrosanguinarine were most potent
(~95-100%) in inhibiting the human colon cancer cell proliferation showing
complete reduction in cell viability. DISCUSSION AND CONCLUSION: This is the
first study on the effect of these alkaloids on SW480 human colon cancer cell
line. This study indicates that some alkaloids of A. mexicana strongly inhibit
the cell proliferation in human colon cancer cells, and it might be a basis for
future development of a potent chemotherapeutic drug.
PMID- 26439488
TI - Child-to-Parent Violence: An Exploratory Study of the Roles of Family Violence
and Parental Discipline Through the Stories Told by Spanish Children and Their
Parents.
AB - The aim of this study was to identify the role of exposure to family violence and
parental discipline in the development of child-to-parent violence (CPV). A
qualitative in-depth interview design was used. Fifteen adolescents (10 boys) who
have perpetrated CPV (Mage=16 years; SDage=1.33 years) and their parents or
foster parents took part in the study. Individually, they answered questions
about exposure to violence and parenting practices. Results suggest that
adolescents were frequently direct victims and also witnesses of violence.
Furthermore, emotional neglect in the parent-child relationship was frequent and
families were characterized by rules that are not consistently implemented.
Different forms of violence seem to coexist in these families, and CPV should
also be a target in the interventions.
PMID- 26439491
TI - Combined Use of GPS and Accelerometry Reveals Fine Scale Three-Dimensional
Foraging Behaviour in the Short-Tailed Shearwater.
AB - Determining the foraging behaviour of free-ranging marine animals is fundamental
for assessing their habitat use and how they may respond to changes in the
environment. However, despite recent advances in bio-logging technology,
collecting information on both at-sea movement patterns and activity budgets
still remains difficult in small pelagic seabird species due to the constraints
of instrument size. The short-tailed shearwater, the most abundant seabird
species in Australia (ca 23 million individuals), is a highly pelagic
procellariiform. Despite its ecological importance to the region, almost nothing
is known about its at-sea behaviour, in particular, its foraging activity. Using
a combination of GPS and tri-axial accelerometer data-loggers, the fine scale
three-dimensional foraging behaviour of 10 breeding individuals from two colonies
was investigated. Five at-sea behaviours were identified: (1) resting on water,
(2) flapping flight, (3) gliding flight, (4) foraging (i.e., surface foraging and
diving events), and (5) taking-off. There were substantial intra- and inter-
individual variations in activity patterns, with individuals spending on average
45.8% (range: 17.1-70.0%) of time at sea resting on water and 18.2% (range: 2.3
49.6%) foraging. Individuals made 76.4 +/- 65.3 dives (range: 8-237) per foraging
trip (mean duration 9.0 +/- 1.9 s), with dives also recorded during night-time.
With the continued miniaturisation of recording devices, the use of combined data
loggers could provide us with further insights into the foraging behaviour of
small procellariiforms, helping to better understand interactions with their
prey.
PMID- 26439493
TI - Improving 4D plan quality for PBS-based liver tumour treatments by combining
online image guided beam gating with rescanning.
AB - Pencil beam scanned (PBS) proton therapy has many advantages over conventional
radiotherapy, but its effectiveness for treating mobile tumours remains
questionable. Gating dose delivery to the breathing pattern is a well-developed
method in conventional radiotherapy for mitigating tumour-motion, but its
clinical efficiency for PBS proton therapy is not yet well documented. In this
study, the dosimetric benefits and the treatment efficiency of beam gating for
PBS proton therapy has been comprehensively evaluated. A series of dedicated 4D
dose calculations (4DDC) have been performed on 9 different 4DCT(MRI) liver data
sets, which give realistic 4DCT extracting motion information from 4DMRI. The
value of 4DCT(MRI) is its capability of providing not only patient geometries and
deformable breathing characteristics, but also includes variations in the
breathing patterns between breathing cycles. In order to monitor target motion
and derive a gating signal, we simulate time-resolved beams' eye view (BEV) x-ray
images as an online motion surrogate. 4DDCs have been performed using three
amplitude-based gating window sizes (10/5/3 mm) with motion surrogates derived
from either pre-implanted fiducial markers or the diaphragm. In addition, gating
has also been simulated in combination with up to 19 times rescanning using
either volumetric or layered approaches. The quality of the resulting 4DDC plans
has been quantified in terms of the plan homogeneity index (HI), total treatment
time and duty cycle. Results show that neither beam gating nor rescanning alone
can fully retrieve the plan homogeneity of the static reference plan. Especially
for variable breathing patterns, reductions of the effective duty cycle to as low
as 10% have been observed with the smallest gating rescanning window (3 mm),
implying that gating on its own for such cases would result in much longer
treatment times. In addition, when rescanning is applied on its own, large
differences between volumetric and layered rescanning have been observed as a
function of increasing number of re-scans. However, once gating and rescanning is
combined, HI to within 2% of the static plan could be achieved in the clinical
target volume, with only moderately prolonged treatment times, irrespective of
the rescanning strategy used. Moreover, these results are independent of the
motion surrogate used. In conclusion, our results suggest image guided beam
gating, combined with rescanning, is a feasible, effective and efficient motion
mitigation approach for PBS-based liver tumour treatments.
PMID- 26439489
TI - The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key
Features of the Human Disease.
AB - The development of effective neuroprotective therapies for Parkinson's disease
(PD) has been severely hindered by the notable lack of an appropriate animal
model for preclinical screening. Indeed, most models currently available are
either acute in nature or fail to recapitulate all characteristic features of the
disease. Here, we present a novel progressive model of PD, with behavioural and
cellular features that closely approximate those observed in patients. Chronic
exposure to dietary phytosterol glucosides has been found to be neurotoxic. When
fed to rats, beta-sitosterol beta-d-glucoside (BSSG) triggers the progressive
development of parkinsonism, with clinical signs and histopathology beginning to
appear following cessation of exposure to the neurotoxic insult and continuing to
develop over several months. Here, we characterize the progressive nature of this
model, its non-motor features, the anatomical spread of synucleinopathy, and
response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding
for 4 months triggered the progressive development of a parkinsonian phenotype
and pathological events that evolved slowly over time, with neuronal loss
beginning only after toxin exposure was terminated. At approximately 3 months
following initiation of BSSG exposure, animals displayed the early emergence of
an olfactory deficit, in the absence of significant dopaminergic nigral cell loss
or locomotor deficits. Locomotor deficits developed gradually over time,
initially appearing as locomotor asymmetry and developing into
akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage
cognitive impairment was observed in the form of spatial working memory deficits,
as assessed by the radial arm maze. In addition to the progressive loss of TH+
cells in the substantia nigra, the appearance of proteinase K-resistant
intracellular alpha-synuclein aggregates was also observed to develop
progressively, appearing first in the olfactory bulb, then the striatum, the
substantia nigra and, finally, hippocampal and cortical regions. The slowly
progressive nature of this model, together with its construct, face and
predictive validity, make it ideal for the screening of potential neuroprotective
therapies for the treatment of PD.
PMID- 26439490
TI - The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and
Close Relative Emmonsia.
AB - Three closely related thermally dimorphic pathogens are causal agents of major
fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis
and paracoccidioidomycosis. Here we report the genome sequence and analysis of
four strains of the etiological agent of blastomycosis, Blastomyces, and two
species of the related genus Emmonsia, typically pathogens of small mammals.
Compared to related species, Blastomyces genomes are highly expanded, with long,
often sharply demarcated tracts of low GC-content sequence. These GC-poor
isochore-like regions are enriched for gypsy elements, are variable in total size
between isolates, and are least expanded in the avirulent B. dermatitidis strain
ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of
similar regions in related species suggests these isochore-like regions
originated recently in the ancestor of the Blastomyces lineage. While gene
content is highly conserved between Blastomyces and related fungi, we identified
changes in copy number of genes potentially involved in host interaction,
including proteases and characterized antigens. In addition, we studied gene
expression changes of B. dermatitidis during the interaction of the infectious
yeast form with macrophages and in a mouse model. Both experiments highlight a
strong antioxidant defense response in Blastomyces, and upregulation of
dioxygenases in vivo suggests that dioxide produced by antioxidants may be
further utilized for amino acid metabolism. We identify a number of functional
categories upregulated exclusively in vivo, such as secreted proteins, zinc
acquisition proteins, and cysteine and tryptophan metabolism, which may include
critical virulence factors missed before in in vitro studies. Across the
dimorphic fungi, loss of certain zinc acquisition genes and differences in amino
acid metabolism suggest unique adaptations of Blastomyces to its host
environment. These results reveal the dynamics of genome evolution and of factors
contributing to virulence in Blastomyces.
PMID- 26439494
TI - What's in the Gift? Towards a Molecular Dissection of Nuptial Feeding in a
Cricket.
AB - Nuptial gifts produced by males and transferred to females during copulation are
common in insects. Yet, their precise composition and subsequent physiological
effects on the female recipient remain unresolved. Male decorated crickets
Gryllodes sigillatus transfer a spermatophore to the female during copulation
that is composed of an edible gift, the spermatophylax, and the ampulla that
contains the ejaculate. After transfer of the spermatophore, the female detaches
the spermatophylax and starts to eat it while sperm from the ampulla are
evacuated into the female reproductive tract. When the female has finished
consuming the spermatophylax, she detaches the ampulla and terminates sperm
transfer. Hence, one simple function of the spermatophylax is to ensure complete
sperm transfer by distracting the female from prematurely removing the ampulla.
However, the majority of orally active components of the spermatophylax itself
and their subsequent effects on female behavior have not been identified. Here,
we report the first analysis of the proteome of the G. sigillatus spermatophylax
and the transcriptome of the male accessory glands that make these proteins. The
accessory gland transcriptome was assembled into 17,691 transcripts whilst about
30 proteins were detected within the mature spermatophylax itself. Of these 30
proteins, 18 were encoded by accessory gland encoded messages. Most
spermatophylax proteins show no similarity to proteins with known biological
functions and are therefore largely novel. A spermatophylax protein shows
similarity to protease inhibitors suggesting that it may protect the biologically
active components from digestion within the gut of the female recipient. Another
protein shares similarity with previously characterized insect polypeptide growth
factors suggesting that it may play a role in altering female reproductive
physiology concurrent with fertilization. Characterization of the spermatophylax
proteome provides the first step in identifying the genes encoding these proteins
in males and in understanding their biological functions in the female recipient.
PMID- 26439486
TI - Consensus Paper: Cerebellar Development.
AB - The development of the mammalian cerebellum is orchestrated by both cell
autonomous programs and inductive environmental influences. Here, we describe the
main processes of cerebellar ontogenesis, highlighting the neurogenic strategies
used by developing progenitors, the genetic programs involved in cell fate
specification, the progressive changes of structural organization, and some of
the better-known abnormalities associated with developmental disorders of the
cerebellum.
PMID- 26439495
TI - Transcriptomic Analysis of Trout Gill Ionocytes in Fresh Water and Sea Water
Using Laser Capture Microdissection Combined with Microarray Analysis.
AB - Fish gills represent a complex organ composed of several cell types that perform
multiple physiological functions. Among these cells, ionocytes are implicated in
the maintenance of ion homeostasis. However, because the ionocyte represents only
a small percent of whole gill tissue, its specific transcriptome can be
overlooked among the numerous cell types included in the gill. The objective of
this study is to better understand ionocyte functions by comparing the RNA
expression of this cell type in freshwater and seawater acclimated rainbow trout.
To realize this objective, ionocytes were captured from gill cryosections using
laser capture microdissection after immunohistochemistry. Then, transcriptome
analyses were performed on an Agilent trout oligonucleotide microarray. Gene
expression analysis identified 108 unique annotated genes differentially
expressed between freshwater and seawater ionocytes, with a fold change higher
than 3. Most of these genes were up-regulated in freshwater cells. Interestingly,
several genes implicated in ion transport, extracellular matrix and structural
cellular proteins appeared up-regulated in freshwater ionocytes. Among them,
several ion transporters, such as CIC2, SLC26A6, and NBC, were validated by qPCR
and/or in situ hybridization. The latter technique allowed us to localize the
transcripts of these ion transporters in only ionocytes and more particularly in
the freshwater cells. Genes involved in metabolism and also several genes
implicated in transcriptional regulation, cell signaling and the cell cycle were
also enhanced in freshwater ionocytes. In conclusion, laser capture
microdissection combined with microarray analysis allowed for the determination
of the transcriptional signature of scarce cells in fish gills, such as
ionocytes, and aided characterization of the transcriptome of these cells in
freshwater and seawater acclimated trout.
PMID- 26439497
TI - Molecular dynamics simulation study of distribution and dynamics of aqueous
solutions of uranyl ions: the effect of varying temperature and concentration.
AB - Investigating the characteristics of actinyl ions has been of great interest due
to their direct relevance in the nuclear fuel cycle. All-atom molecular dynamics
simulations have been employed to study the orientational structure and dynamics
of aqueous solutions of uranyl ions of various concentrations. The orientational
structure of water around a uranyl ion has been thoroughly investigated by
calculating different orientational probability distributions corresponding to
different molecular axes of water. The orientational distribution of water
molecules in the first coordination shell of a uranyl ion is found to be markedly
different from that in bulk water. Analysis of counterion distribution around the
uranyl ion reveals the presence of nitrate ions along with water molecules in the
first solvation shell. From the comparison of the number of coordinated water and
nitrate ions at various uranyl nitrate concentrations, it is evident that these
two species compete for occupying the first solvation shell of the uranyl ion.
Orientational dynamics of water molecules about different molecular axes of water
in the vicinity of uranyl ions have also been investigated and decreasing
orientational mobility of water with increasing uranyl concentration has been
found. However, it is observed that the orientational dynamics remains more or
less the same whether we consider all the water molecules in the aqueous solution
or only the solvation shell water molecules. The effect of temperature on the
translational and orientational characteristics of the aqueous uranyl solutions
has also been studied in detail.
PMID- 26439496
TI - The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human
Cancers.
AB - Adenosine-to-inosine (A-to-I) RNA editing is a widespread post-transcriptional
mechanism, but its genomic landscape and clinical relevance in cancer have not
been investigated systematically. We characterized the global A-to-I RNA editing
profiles of 6,236 patient samples of 17 cancer types from The Cancer Genome Atlas
and revealed a striking diversity of altered RNA-editing patterns in tumors
relative to normal tissues. We identified an appreciable number of clinically
relevant editing events, many of which are in noncoding regions. We
experimentally demonstrated the effects of several cross-tumor nonsynonymous RNA
editing events on cell viability and provide the evidence that RNA editing could
selectively affect drug sensitivity. These results highlight RNA editing as an
exciting theme for investigating cancer mechanisms, biomarkers, and treatments.
PMID- 26439498
TI - Host Transcriptional Profiles and Immunopathologic Response following
Mycobacterium avium subsp. paratuberculosis Infection in Mice.
AB - Paratuberculosis or Johne's disease is a chronic granulomatous enteropathy in
ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection.
In the present study, we examined the host response to MAP infection in spleens
of mice in order to investigate the host immunopathology accompanying host
pathogen interaction. Transcriptional profiles of the MAP-infected mice at 3 and
6 weeks p.i. showed severe histopathological changes, whereas those at 12 weeks
p.i. displayed reduced lesion severity in the spleen and liver. MAP-infected mice
at 3 and 6 weeks p.i. showed up-regulation of interferon-related genes, scavenger
receptor, and complement components, suggesting an initial innate immune
reaction, such as macrophage activation, bactericidal activity, and macrophage
invasion of MAP. Concurrently, MAP-infected mice at 3 and 6 weeks p.i. were also
suggested to express M2 macrophage phenotype with up-regulation of Mrc1, and
Marco and down-regulation of MHC class II, Ccr7, and Irf5, and canonical pathways
related to the T cell response including ICOS-ICOSL signaling in T helper cells,
calcium-induced T lymphocyte apoptosis, and CD28 signaling in T helper cell.
These results provide information which furthers the understanding of the
immunopathologic response to MAP infection in mice, thereby providing insights
valuable for research into the pathogenesis for MAP infection.
PMID- 26439499
TI - Comparison of intra-ocular pressure changes with liquid or flat applanation
interfaces in a femtosecond laser platform.
AB - Cataract surgery is the most common surgical procedure and femtosecond laser
assisted cataract surgery (FLACS) has gained increased popularity. FLACS requires
the application of a suction device to stabilize the laser head and focus the
laser beam accurately. This may cause a significant escalation in intra-ocular
pressure (IOP), which poses potential risks for patients undergoing cataract
surgery. In this study we aimed to assess the effect of the Ziemer LDV Z8
femtosecond cataract machine on IOP. We demonstrated through a porcine model that
IOP was significantly higher with a flat interface but could be abrogated by
reducing surgical compression and vacuum. Pressure was lower with a liquid
interface, and further altering angulation of the laser arm could reduce the IOP
to 36 mmHg. A pilot series in patients showed comparable pressure rises with the
porcine model (30 mmHg). These strategies may improve the safety profile in
patients vulnerable to high pressure when employing FLACS with the Ziemer LDV Z8.
PMID- 26439501
TI - Genetic Tailors: CTCF and Cohesin Shape the Genome During Evolution.
AB - Research into chromosome structure and organization is an old field that has seen
some fascinating progress in recent years. Modern molecular methods that can
describe the shape of chromosomes have begun to revolutionize our understanding
of genome organization and the mechanisms that regulate gene activity. A picture
is beginning to emerge of chromatin loops representing a widespread organizing
principle of the chromatin fiber and the proteins cohesin and CCCTC-binding
factor (CTCF) as key players anchoring such chromatin loops. Here we review our
current understanding of the features of CTCF- and cohesin-mediated genome
organization and how their evolution may have helped to shape genome structure.
PMID- 26439502
TI - Dating Tips for Divergence-Time Estimation.
AB - The molecular clock is the only viable means of establishing an accurate
timescale for Life on Earth, but it remains reliant on a capricious fossil record
for calibration. 'Tip-dating' promises a conceptual advance, integrating fossil
species among their living relatives using molecular/morphological datasets and
evolutionary models. Fossil species of known age establish calibration directly,
and their phylogenetic uncertainty is accommodated through the co-estimation of
time and topology. However, challenges remain, including a dearth of effective
models of morphological evolution, rate correlation, the non-random nature of
missing characters in fossil data, and, most importantly, accommodating
uncertainty in fossil age. We show uncertainty in fossil-dating propagates to
divergence-time estimates, yielding estimates that are older and less precise
than those based on traditional node calibration. Ultimately, node and tip
calibrations are not mutually incompatible and may be integrated to achieve more
accurate and precise evolutionary timescales.
PMID- 26439500
TI - The Brain Activity in Brodmann Area 17: A Potential Bio-Marker to Predict Patient
Responses to Antiepileptic Drugs.
AB - In this study, we aimed to predict newly diagnosed patient responses to
antiepileptic drugs (AEDs) using resting-state functional magnetic resonance
imaging tools to explore changes in spontaneous brain activity. We recruited 21
newly diagnosed epileptic patients, 8 drug-resistant (DR) patients, 11 well
healed (WH) patients, and 13 healthy controls. After a 12-month follow-up, 11
newly diagnosed epileptic patients who showed a poor response to AEDs were placed
into the seizures uncontrolled (SUC) group, while 10 patients were enrolled in
the seizure-controlled (SC) group. By calculating the amplitude of fractional low
frequency fluctuations (fALFF) of blood oxygen level-dependent signals to measure
brain activity during rest, we found that the SUC patients showed increased
activity in the bilateral occipital lobe, particularly in the cuneus and lingual
gyrus compared with the SC group and healthy controls. Interestingly, DR patients
also showed increased activity in the identical cuneus and lingual gyrus regions,
which comprise Brodmann's area 17 (BA17), compared with the SUC patients;
however, these abnormalities were not observed in SC and WH patients. The
receiver operating characteristic (ROC) curves indicated that the fALFF value of
BA17 could differentiate SUC patients from SC patients and healthy controls with
sufficient sensitivity and specificity prior to the administration of medication.
Functional connectivity analysis was subsequently performed to evaluate the
difference in connectivity between BA17 and other brain regions in the SUC, SC
and control groups. Regions nearby the cuneus and lingual gyrus were found
positive connectivity increased changes or positive connectivity changes with
BA17 in the SUC patients, while remarkably negative connectivity increased
changes or positive connectivity decreased changes were found in the SC patients.
Additionally, default mode network (DMN) regions showed negative connectivity
increased changes or negative changes with BA17 in the SUC patients. The abnormal
increased in BA17 activity may be a key point that plays a substantial role in
facilitating seizure onset.
PMID- 26439503
TI - Reaching Consensus by Allowing Moments of Indecision.
AB - Group decision-making processes often turn into a drawn out and costly battle
between two opposing subgroups. Using analytical arguments based on a master
equation description of the opinion dynamics occurring in a three-state model of
cooperatively interacting units, we show how the capability of a social group to
reach consensus can be enhanced when there is an intermediate state for
indecisive individuals to pass through. The time spent in the intermediate state
must be relatively short compared to that of the two polar states in order to
create the beneficial effect. Furthermore, the cooperation between individuals
must not be too low, as the benefit to consensus is possible only when the
cooperation level exceeds a specific threshold. We also discuss how zealots,
agents that remain in one state forever, can affect the consensus among the rest
of the population by counteracting the benefit of the intermediate state or
making it virtually impossible for an opposition to form.
PMID- 26439504
TI - Clinical Implication of Serine Metabolism-Associated Enzymes in Colon Cancer.
AB - PURPOSE: Recently, enzymes of the serine synthetic pathway (SSP) have been
suggested as key player in the metabolic adaptation of oncogenesis. We assessed
the expression of enzymes of the SSP in colonic tumor tissue (TT) and paired
normal tissue (pNT) and the prognostic implications. METHODS: From 2006 to 2010,
we included 486 patients with colon cancer who underwent curative surgery at
Kyungpook National University Hospital. Phosphoglycerate dehydrogenase (PHGDH),
pyruvate dehydrogenase kinase (PDK) 1, PDK2, pyruvate kinase M2 (PKM2), and
phosphoserine aminotransferase (PSAT) expression were investigated by
immunohistochemical staining (IHC) in TT and pNT. The IHC values were calculated
by multiplying intensity by proportion. The final score was classified as
follows: 0-2 as negative and 3-12 as positive. RESULTS: During the median follow
up duration of 55.5 months (37.4-90.6), 78 patients experienced recurrence. The
expression of PHGDH, PDK1, and PSAT was significantly higher in TT than pNT (p <
0.001 for each). The univariate analysis for relapse-free survival revealed that
TT PDK2 positivity was the only positive prognostic factor (p = 0.023). However,
the expression of TT PDK2 did not represent a prognostic value in multivariate
analysis. CONCLUSIONS: In conclusion, PHGDH, PDK1, and PSAT were significantly
increased in colonic TT compared with pNT. The prognostic implication of these
enzymes needs to be further investigated.
PMID- 26439505
TI - Prostate cancer: Wnt signalling induces resistance.
PMID- 26439506
TI - Infection: PrEParation to be PROUD of.
PMID- 26439507
TI - Prostate cancer: How to differenti-8 Gleason scores?
PMID- 26439508
TI - Self-reported Occupational Skin Exposure and Risk of Physician-certified Long
term Sick Leave: A Prospective Study of the General Working Population of Norway.
AB - Little is known about the contribution of occupational skin exposure as a risk
factor for physician-certified long-term sick leave in the general working
population of Norway. This study drew a cohort (n = 12,255; response at baseline
69.9%) randomly from the general population of Norway. Occupational skin exposure
(in 2009) was measured based on 5 items. The outcome of interest was physician
certified long-term sick leave >= 16 days during 2010. Statistical adjustment for
psychosocial and mechanical occupational exposures was performed. Long-term sick
leave was predicted by occupational skin exposure to cleaning products (odds
ratio (OR) 1.7; 95% confidence interval (95% CI) 1.1-2.5) and waste (OR 2.1; 95%
CI 1.1-3.7) among men, and occupational skin exposure to water (OR 1.3; 95% CI
1.0-1.6) among women. The estimated population attributable risk for occupational
skin exposure was 14.5%, which emphasizes its contribution as an important risk
factor for long-term sick leave.
PMID- 26439509
TI - Hydrodynamic schooling of flapping swimmers.
AB - Fish schools and bird flocks are fascinating examples of collective behaviours in
which many individuals generate and interact with complex flows. Motivated by
animal groups on the move, here we explore how the locomotion of many bodies
emerges from their flow-mediated interactions. Through experiments and
simulations of arrays of flapping wings that propel within a collective wake, we
discover distinct modes characterized by the group swimming speed and the spatial
phase shift between trajectories of neighbouring wings. For identical flapping
motions, slow and fast modes coexist and correspond to constructive and
destructive wing-wake interactions. Simulations show that swimming in a group can
enhance speed and save power, and we capture the key phenomena in a mathematical
model based on memory or the storage and recollection of information in the flow
field. These results also show that fluid dynamic interactions alone are
sufficient to generate coherent collective locomotion, and thus might suggest new
ways to characterize the role of flows in animal groups.
PMID- 26439510
TI - Optical antennas with multiple plasmonic nanoparticles for tip-enhanced Raman
microscopy.
AB - Tip-enhanced Raman spectroscopy (TERS) has recently become one of the most
important tools for analyzing advanced nano-devices and nano-materials, because
it allows strong enhancement of weak Raman signal from the nanometric volume of a
sample. However, consistent enhancement in TERS is still an issue and scientists
have been struggling to fabricate good tips for reliable, strong and reproducible
enhancement. There is a strong need to study the morphology and the arrangement
of metal nanostructures near the tip apex for efficient plasmonic enhancement in
TERS. Here, we present a study on the metal grains attached to the tip surface
for producing higher and much consistent enhancement in TERS. Our study shows
that the plasmonic enhancement strongly depends on the number of grains and on
the their separations. We found through simulations that multiple grains arranged
closely but discretely on a dielectric probe act as an efficient plasmonic
antenna and that enhancement in TERS is maximum for an optimized number of
grains. The number of grains and the nano-gap between them are crucial for
reproducible enhancement. This promising result, which we also demonstrate and
prove by experiments, will bring TERS to a new level, where it can be utilized
with more confidence of large reproducible enhancement for those nano-sized
samples that have extremely weak Raman scattering.
PMID- 26439511
TI - Carbon dioxide capture and utilization: using dinuclear catalysts to prepare
polycarbonates.
AB - The copolymerization of epoxides, including cyclohexene oxide and vinyl
cyclohexene oxide with carbon dioxide are presented. These processes are
catalyzed using a homogeneous di-zinc complex that shows good activity and very
high selectivities for polycarbonate polyol formation. The polymerizations are
investigated in the presence of different amounts of exogenous reagents,
including water, diols and diamines, as models for common contaminants in any
carbon dioxide capture and utilization scenario.
PMID- 26439512
TI - Coalescence of drops in a 2D microchannel: critical transitions to autocatalytic
behaviour.
AB - A single coalescence event in a 2D concentrated emulsion in a microchannel can
trigger an avalanche of similar events that can destabilize the entire assembly
of drops. The sensitive dependence of the process on numerous parameters makes
the propagation dynamics appear probabilistic. In this article, a stochastic
simulation framework is proposed to understand this collective behavior in a
system employing a large number of drops. We discover that the coalescence
propagation dynamics exhibit a critical behavior where two outcomes are favored:
no avalanche and large avalanches. Our analysis reveals that this behavior is a
result of the inherent autocatalytic nature of the process. The effect of the
aspect ratio of the drop assembly on the propagation dynamics is studied. We
generate a parametric plot that shows the region of the parameter space where the
propagation, averaged over the ensemble, is autocatalytic: where the possibility
of near destabilization of the drop assembly appears.
PMID- 26439514
TI - The Washington University Central Neuroimaging Data Archive.
AB - Since the early 2000's, much of the neuroimaging work at Washington University
(WU) has been facilitated by the Central Neuroimaging Data Archive (CNDA), an
XNAT-based imaging informatics system. The CNDA is uniquely related to XNAT, as
it served as the original codebase for the XNAT open source platform. The CNDA
hosts data acquired in over 1000 research studies, encompassing 36,000 subjects
and more than 60,000 imaging sessions. Most imaging modalities used in modern
human research are represented in the CNDA, including magnetic resonance (MR),
positron emission tomography (PET), computed tomography (CT), nuclear medicine
(NM), computed radiography (CR), digital radiography (DX), and ultrasound (US).
However, the majority of the imaging data in the CNDA are MR and PET of the human
brain. Currently, about 20% of the total imaging data in the CNDA is available by
request to external researchers. CNDA's available data includes large sets of
imaging sessions and in some cases clinical, psychometric, tissue, or genetic
data acquired in the study of Alzheimer's disease, brain metabolism, cancer, HIV,
sickle cell anemia, and Tourette syndrome.
PMID- 26439515
TI - Mechanisms of hemispheric lateralization: Asymmetric interhemispheric recruitment
in the face perception network.
AB - Perceiving human faces constitutes a fundamental ability of the human mind,
integrating a wealth of information essential for social interactions in everyday
life. Neuroimaging studies have unveiled a distributed neural network consisting
of multiple brain regions in both hemispheres. Whereas the individual regions in
the face perception network and the right-hemispheric dominance for face
processing have been subject to intensive research, the functional integration
among these regions and hemispheres has received considerably less attention.
Using dynamic causal modeling (DCM) for fMRI, we analyzed the effective
connectivity between the core regions in the face perception network of healthy
humans to unveil the mechanisms underlying both intra- and interhemispheric
integration. Our results suggest that the right-hemispheric lateralization of the
network is due to an asymmetric face-specific interhemispheric recruitment at an
early processing stage - that is, at the level of the occipital face area (OFA)
but not the fusiform face area (FFA). As a structural correlate, we found that
OFA gray matter volume was correlated with this asymmetric interhemispheric
recruitment. Furthermore, exploratory analyses revealed that interhemispheric
connection asymmetries were correlated with the strength of pupil constriction in
response to faces, a measure with potential sensitivity to holistic (as opposed
to feature-based) processing of faces. Overall, our findings thus provide a
mechanistic description for lateralized processes in the core face perception
network, point to a decisive role of interhemispheric integration at an early
stage of face processing among bilateral OFA, and tentatively indicate a relation
to individual variability in processing strategies for faces. These findings
provide a promising avenue for systematic investigations of the potential role of
interhemispheric integration in future studies.
PMID- 26439513
TI - White matter microstructure mediates the relationship between cardiorespiratory
fitness and spatial working memory in older adults.
AB - White matter structure declines with advancing age and has been associated with a
decline in memory and executive processes in older adulthood. Yet, recent
research suggests that higher physical activity and fitness levels may be
associated with less white matter degeneration in late life, although the tract
specificity of this relationship is not well understood. In addition, these prior
studies infrequently associate measures of white matter microstructure to
cognitive outcomes, so the behavioral importance of higher levels of white matter
microstructural organization with greater fitness levels remains a matter of
speculation. Here we tested whether cardiorespiratory fitness (VO2max) levels
were associated with white matter microstructure and whether this relationship
constituted an indirect pathway between cardiorespiratory fitness and spatial
working memory in two large, cognitively and neurologically healthy older adult
samples. Diffusion tensor imaging was used to determine white matter
microstructure in two separate groups: Experiment 1, N=113 (mean age=66.61) and
Experiment 2, N=154 (mean age=65.66). Using a voxel-based regression approach, we
found that higher VO2max was associated with higher fractional anisotropy (FA), a
measure of white matter microstructure, in a diverse network of white matter
tracts, including the anterior corona radiata, anterior internal capsule, fornix,
cingulum, and corpus callosum (PFDR-corrected<.05). This effect was consistent
across both samples even after controlling for age, gender, and education.
Further, a statistical mediation analysis revealed that white matter
microstructure within these regions, among others, constituted a significant
indirect path between VO2max and spatial working memory performance. These
results suggest that greater aerobic fitness levels are associated with higher
levels of white matter microstructural organization, which may, in turn, preserve
spatial memory performance in older adulthood.
PMID- 26439516
TI - QSAR model for predicting cell viability of human embryonic kidney cells exposed
to SiO2 nanoparticles.
AB - A predictive model for the viability (%) of cultured human embryonic kidney cells
(HEK293) exposed to 20 and 50 nm silica nanoparticles was built using 'optimal
descriptors' as mathematical functions of size, concentration and exposure time.
The calculation was carried out with CORAL software
(http://www.insilico.eu/coral/) on five random splits of combined systems
(particle size-particle concentration-cell exposure time) into training,
calibration, and validation sets. The R(2) values of the best models were above
0.68. The average statistical quality of the model for the viability (%) of
HEK293 exposed to different concentrations of silica nanoparticles measured by
MTT assay is satisfactory.
PMID- 26439517
TI - Source apportionment and health risk assessment of trace metals in surface soils
of Beijing metropolitan, China.
AB - Understanding the exposure risks of trace metals in contamination soils and
apportioning their sources are the basic preconditions for soil pollution
prevention and control. In this study, a detailed investigation was conducted to
assess the health risks of trace metals in surface soils of Beijing which is one
of the most populated cities in the world and to apportion their potential
sources. The data set of metals for 12 elements in 240 soil samples was
collected. Pollution index and enrichment factor were used to identify the
general contamination characteristic of soil metals. The probabilistic risk model
was employed for health risk assessment, and a chemometrics technique,
multivariate curve resolution-weighted alternating least squares (MCR-WALS), was
applied to apportion sources. Results suggested that the soils in Beijing
metropolitan region were contaminated by Hg, Cd, Cu, As, and Pb in varying
degree, lying in the moderate pollution level. As a whole, the health risks posed
by soil metals were acceptable or close to tolerable. Comparatively speaking,
children and adult females were the relatively vulnerable populations for the non
carcinogenic and carcinogenic risks, respectively. Atmospheric deposition,
fertilizers and agrochemicals, and natural source were apportioned as the
potential sources determining the contents of trace metals in soils of Beijing
area with contributions of 15.5%-16.4%, 5.9%-7.7% and 76.0%-78.6%, respectively.
PMID- 26439518
TI - Fluoride decreased the sperm ATP of mice through inhabiting mitochondrial
respiration.
AB - Fluoride-induced low sperm motility was observed in accumulated investigations.
However, the effect of fluoride exposure on ATP generation which is essential to
sperm motility remains to be elucidated. In this study, 120 healthy male mice
were orally administrated with 0, 25, 50, and 100 mg L(-1) NaF for 90 d. Results
showed that compared with controls, fluoride ingestion significantly reduced
sperm count, survival, as well as mobility and total ATP level in sperm untreated
with carbonyl cyanide m-chlorophenylhydrazone (CCCP) or pyruvate, which was used
to establish glycolysis or mitochondrial respiration model, respectively. Data
further revealed that sperm mobility and ATP level under mitochondrial
respiration condition were significantly suppressed, while no statistical
difference occurred in the model of glycolysis, indicating ATP derived from
mitochondria was affected. Moreover, mRNA expressions of mitochondrial cytochrome
b (mt-Cytb) and cytochrome c oxidase subunit 2 (mt-COX2), two important molecules
in mitochondrial electron transport chain (ETC), were down-regulated in all
fluoride treatment groups. Mitochondria in sperm of mice exposed to 100 mg L(-1)
NaF appeared to be irregular and vacuolated. These findings suggested that
decreased sperm motility induced by fluoride may result from low ATP generation
due to the disturbed ETC in sperm mitochondrial.
PMID- 26439519
TI - Influence of nitrite accumulation on "Candidatus Accumulibacter" population
structure and enhanced biological phosphorus removal from municipal wastewater.
AB - A modified University of Cape Town (MUCT) process was used to treat real
municipal wastewater with low carbon to nitrogen ratio (C/N). To our knowledge,
this is the first study where the influence of nitrite accumulation on
"Candidatus Accumulibacter" clade-level population structure was investigated
during nitritation establishment and destruction. Real time quantitative PCR
assays were conducted using the polyphosphate kinase 1 gene (ppk1) as a genetic
marker. Abundances of total "Candidatus Accumulibacter", the relative
distributions and population structure of the five "Candidatus Accumulibacter"
clades were characterized. Under complete nitrification, clade I using nitrate as
electron acceptor was below 5% of total "Candidatus Accumulibacter". When the
reactor was transformed into nitritation, clade I gradually disappeared. Clade
IID using nitrite as electron acceptor for denitrifying phosphorus (P) removal
was always the dominant "Candidatus Accumulibacter" throughout the operational
period. This clade was above 90% on average in total "Candidatus Accumulibacter",
even up to nearly 100%, which was associated with good performance of
denitrifying P removal via nitrite pathway. The nitrite concentrations affected
the abundance of clade IID. The P removal was mainly completed by anoxic P uptake
of about 88%. The P removal efficiency clearly had a positive correlation with
the nitrite accumulation ratio. Under nitritation, the P removal efficiency was
30% higher than that under complete nitrification, suggesting that nitrite was
appropriate as electron acceptor for denitrifying P removal when treating carbon
limited wastewater.
PMID- 26439520
TI - The key to accuracy of zygoma repositioning: Suitability of the SynpliciTi
customized guide-plates.
AB - This study aimed at assessing the suitability and accuracy for secondary zygoma
repositioning of custom-made drilling guides and plates designed from a computer
assisted reversed planning. Mini-plates and pre-drilling guides were designed
starting from the virtual planning of the repositioned zygoma. The pilot holes
were drilled first during surgery. The zygoma was repositioned by inserting the
screws in the pilot holes using the custom-made plates. Surgical planning and
postoperative CT-scan were superimposed. The distances between each point of the
planned and final zygoma positions indicated the accuracy of repositioning. We
included 11 zygoma repositioning procedures in 10 consecutive patients. The
medians of the distances between the planned and final zygoma positions in this
cohort ranged from 0.05 mm to 0.38 mm (0.20 mm on average). 93%, 81%, and 57% of
the points of the planned and final zygoma were less than 2 mm, 1 mm, and 0.5 mm
away, respectively. The SynpliciTi customized guide-plate system allowed
achieving highly accurate zygoma repositioning in short operative times in this
series, without the need for expensive equipment with difficult implementation.
Larger cohorts are needed to assess the overall benefit and cost-effectiveness of
the SynpliciTi.
PMID- 26439521
TI - Changes in anteroposterior position and inclination of the maxillary incisors
after surgical-orthodontic treatment of skeletal class III malocclusions.
AB - PURPOSE: The purpose of this study was to evaluate and compare the
anteroposterior (AP) position and inclination of the maxillary incisors in
subjects with class I normal occlusion and a harmonious profile with patients
with skeletal class III malocclusions, and to investigate the changes in
maxillary incisor inclination and AP position after surgical-orthodontic
treatment in class III patients. MATERIAL AND METHODS: Sixty-five subjects (35
female and 30 male; mean age: 21.8 +/- 3.89 years) with normal profiles and class
I skeletal and dental patterns were selected as a control sample. Sixty-seven
patients (38 female and 29 male; mean age: 21.3 +/- 3.31 years) with skeletal and
dental class III malocclusions who sought surgical-orthodontic treatment were
used as the study sample. Subjects were asked to smile and profile photographs
were taken with the head in a natural position and the maxillary central incisors
and the forehead in full view; cephalograms were taken and superimposed on the
profile pictures according to the outline of the forehead and nose. Forehead
inclination, maxillary incisor facial inclination and the AP position of the
maxillary central incisor relative to the forehead (FAFFA) were measured on the
integrated images and statistical analyses were performed. RESULTS: In both
groups, there were no significant male/female differences in either the maxillary
central incisor inclination or AP position. Female subjects had a significantly
steeper forehead inclination compared with males (P < 0.001) in both groups.
After combined surgical-orthodontic treatment, the significant labial inclination
(P < 0.001) and posterior positioning (P < 0.001) of the maxillary central
incisors had been corrected to close to normal range (P > 0.05). In the control
group, 84.6% had the facial axial point (FA) of their maxillary central incisors
positioned between lines through the forehead facial axis (FFA) point and the
glabella. In the study group, however, 79.1% had the maxillary central incisors
positioned posterior to the line through the FFA point and the difference with
the control group was statistically significant (P < 0.001). The position of the
maxillary central incisors was strongly correlated with forehead inclination in
the control sample (r(2) = 0.456; P < 0.01), but only a poor correlation was
detected in the class III group (r(2) = 0.177; P > 0.05). CONCLUSIONS: With the
integrated radiograph-photograph method, the lateral cephalogram was reoriented,
which makes it possible to accurately measure the variables on profile
photographs. The AP position and inclination of the maxillary central incisors
relative to the forehead plays an important role in the esthetics of the profile
during smiling and could be an important variable to be considered during
diagnosis and treatment planning.
PMID- 26439522
TI - Walking with eyes closed is easier than walking with eyes open without visual
cues: The Romberg task versus the goggle task.
AB - BACKGROUND: The Romberg test, with the subject standing and with eyes closed,
gives diagnostic arguments for a proprioceptive disorder. Closing the eyes is
also used in balance rehabilitation as a main way to stimulate neural plasticity
with proprioceptive, vestibular and even cerebellar disorders. Nevertheless,
standing and walking with eyes closed or with eyes open in the dark are certainly
2 different tasks. We aimed to compare walking with eyes open, closed and wearing
black or white goggles in healthy subjects. METHODS: A total of 50 healthy
participants were randomly divided into 2 protocols and asked to walk on a 5-m
pressure-sensitive mat, under 3 conditions: (1) eyes open (EO), eyes closed (EC)
and eyes open with black goggles (BG) and (2) EO, EO with BG and with white
goggles (WG). Gait was described by velocity (m.s(-1)), double support (% gait
cycle), gait variability index (GVI/100) and exit from the mat (%). Analysis
involved repeated measures Anova, Holm-Sidak's multiple comparisons test for
parametric parameters (GVI) and Dunn's multiple comparisons test for non
parametric parameters. RESULTS: As compared with walking with EC, walking with BG
produced lower median velocity, by 6% (EO 1.26; BG 1.01 vs EC 1.07 m.s(-1),
P=0.0328), and lower mean GVI, by 8% (EO 91.8; BG 66.8 vs EC 72.24, P=0.009).
Parameters did not differ between walking under the BG and WG conditions.
CONCLUSION: The goggle task increases the difficulty in walking with visual
deprivation compared to the Romberg task, so the goggle task can be proposed to
gradually increase the difficulty in walking with visual deprivation (from eyes
closed to eyes open in black goggles).
PMID- 26439523
TI - Analysis of Chuanxiong Rhizoma and its active components by Fourier transform
infrared spectroscopy combined with two-dimensional correlation infrared
spectroscopy.
AB - As complicated mixture systems, active components of Chuanxiong Rhizoma are very
difficult to identify and discriminate. In this paper, the macroscopic IR
fingerprint method including Fourier transform infrared spectroscopy (FT-IR), the
second derivative infrared spectroscopy (SD-IR) and two-dimensional correlation
infrared spectroscopy (2DCOS-IR), was applied to study and identify Chuanxiong
raw materials and its different segmented production of HPD-100 macroporous
resin. Chuanxiong Rhizoma is rich in sucrose. In the FT-IR spectra, water eluate
is more similar to sucrose than the powder and the decoction. Their second
derivative spectra amplified the differences and revealed the potentially
characteristic IR absorption bands and combined with the correlation coefficient,
concluding that 50% ethanol eluate had more ligustilide than other eluates.
Finally, it can be found from 2DCOS-IR spectra that proteins were extracted by
ethanol from Chuanxiong decoction by HPD-100 macroporous resin. It was
demonstrated that the above three-step infrared spectroscopy could be applicable
for quick, non-destructive and effective analysis and identification of very
complicated and similar mixture systems of traditional Chinese medicines.
PMID- 26439524
TI - SERS substrates fabricated using ceramic filters for the detection of bacteria.
AB - SERS substrates were fabricated by filtering either Ag or Au colloidal particles
onto rigid, ceramic filters - onto which suspensions of bacteria were then
filtered. SERS spectra of the bacteria were obtained using a Raman spectrometer
that has an 'orbital raster scan' capability. It was shown that bacteria samples
prepared in this manner were uniformly distributed onto the surface of the SERS
substrate. The effect of common buffer systems on the SERS spectra was
investigated and the utility of using the SERS technique for speciation of
bacteria was explored.
PMID- 26439525
TI - Mixed hemimicelles solid-phase extraction based on sodium dodecyl sulfate (SDS)
coated nano-magnets for the spectrophotometric determination of Fingolomid in
biological fluids.
AB - In this study, mixed hemimicelles solid-phase extraction (SPE) based on sodium
dodecyl sulfate (SDS)-coated nano-magnets Fe3O4 was investigated as a novel
method for the separation and determination of Fingolimod (FLM) in water, urine
and plasma samples prior to spectrophotometeric determination. Due to the high
surface area of these new sorbents and the excellent adsorption capacity after
surface modification by SDS, satisfactory extraction recoveries can be produced.
The main factors affecting the adsolubilization of analysts, such as pH,
surfactant and adsorbent amounts, ionic strength, extraction time and desorption
conditions were studied and optimized. Under the selected conditions, FLM has
been quantitatively extracted. The accuracy of the method was evaluated by
recovery measurements on spiked samples, and good recoveries of 96%, 95% and 88%
were observed for water, urine and plasma respectively. Proper linear behaviors
over the investigated concentration ranges of 2-26, 2-17 and 2-13 mg/L with good
coefficients of determination, 0.998, 0.997 and 0.995 were achieved for water,
urine and plasma samples, respectively. To the best of our knowledge, this is the
first time that a mixed hemimicelles SPE method based on magnetic separation and
nanoparticles has been used as a simple and sensitive method for monitoring of
FLM in water and biological samples.
PMID- 26439526
TI - Validated derivative and ratio derivative spectrophotometric methods for the
simultaneous determination of levocetirizine dihydrochloride and ambroxol
hydrochloride in pharmaceutical dosage form.
AB - Three simple, precise, accurate and validated derivative spectrophotometric
methods have been developed for the simultaneous determination of levocetirizine
dihydrochloride (LCD) and ambroxol hydrochloride (ABH) in bulk powder and in
pharmaceutical formulations. The first method is a first derivative
spectrophotometric method ((1)D) using a zero-crossing technique of measurement
at 210.4 nm for LCD and at 220.0 nm for ABH. The second method employs a second
derivative spectrophotometry ((2)D) where the measurements were carried out at
242.0 and 224.4 nm for LCD and ABH, respectively. In the third method, the first
derivative of the ratio spectra was calculated and the first derivative of the
ratio amplitudes at 222.8 and 247.2 nm was selected for the determination of LCD
and ABH, respectively. Calibration graphs were established in the ranges of 1.0
20.0 MUg mL(-1) for LCD and 4.0-20.0 MUg mL(-1) for ABH using derivative and
ratio first derivative spectrophotometric methods with good correlation
coefficients. The developed methods have been successfully applied to the
simultaneous determination of both drugs in commercial tablet dosage form.
PMID- 26439527
TI - Cell-Type-Specific Sensorimotor Processing in Striatal Projection Neurons during
Goal-Directed Behavior.
AB - Goal-directed sensorimotor transformation drives important aspects of mammalian
behavior. The striatum is thought to play a key role in reward-based learning and
action selection, receiving glutamatergic sensorimotor signals and dopaminergic
reward signals. Here, we obtain whole-cell membrane potential recordings from the
dorsolateral striatum of mice trained to lick a reward spout after a whisker
deflection. Striatal projection neurons showed strong task-related modulation,
with more depolarization and action potential firing on hit trials compared to
misses. Direct pathway striatonigral neurons, but not indirect pathway
striatopallidal neurons, exhibited a prominent early sensory response.
Optogenetic stimulation of direct pathway striatonigral neurons, but not indirect
pathway striatopallidal neurons, readily substituted for whisker stimulation
evoking a licking response. Our data are consistent with direct pathway
striatonigral neurons contributing a "go" signal for goal-directed sensorimotor
transformation leading to action initiation. VIDEO ABSTRACT.
PMID- 26439528
TI - Even-Skipped(+) Interneurons Are Core Components of a Sensorimotor Circuit that
Maintains Left-Right Symmetric Muscle Contraction Amplitude.
AB - Bilaterally symmetric motor patterns--those in which left-right pairs of muscles
contract synchronously and with equal amplitude (such as breathing, smiling,
whisking, and locomotion)--are widespread throughout the animal kingdom. Yet,
surprisingly little is known about the underlying neural circuits. We performed a
thermogenetic screen to identify neurons required for bilaterally symmetric
locomotion in Drosophila larvae and identified the evolutionarily conserved Even
skipped(+) interneurons (Eve/Evx). Activation or ablation of Eve(+) interneurons
disrupted bilaterally symmetric muscle contraction amplitude, without affecting
the timing of motor output. Eve(+) interneurons are not rhythmically active and
thus function independently of the locomotor CPG. GCaMP6 calcium imaging of
Eve(+) interneurons in freely moving larvae showed left-right asymmetric
activation that correlated with larval behavior. TEM reconstruction of Eve(+)
interneuron inputs and outputs showed that the Eve(+) interneurons are at the
core of a sensorimotor circuit capable of detecting and modifying body wall
muscle contraction.
PMID- 26439529
TI - Cortical and Subcortical Contributions to Short-Term Memory for Orienting
Movements.
AB - Neural activity in frontal cortical areas has been causally linked to short-term
memory (STM), but whether this activity is necessary for forming, maintaining, or
reading out STM remains unclear. In rats performing a memory-guided orienting
task, the frontal orienting fields in cortex (FOF) are considered critical for
STM maintenance, and during each trial display a monotonically increasing neural
encoding for STM. Here, we transiently inactivated either the FOF or the superior
colliculus and found that the resulting impairments in memory-guided orienting
performance followed a monotonically decreasing time course, surprisingly
opposite to the neural encoding. A dynamical attractor model in which STM relies
equally on cortical and subcortical regions reconciled the encoding and
inactivation data. We confirmed key predictions of the model, including a time
dependent relationship between trial difficulty and perturbability, and
substantial, supralinear, impairment following simultaneous inactivation of the
FOF and superior colliculus during memory maintenance.
PMID- 26439530
TI - A Large-Scale Circuit Mechanism for Hierarchical Dynamical Processing in the
Primate Cortex.
AB - We developed a large-scale dynamical model of the macaque neocortex, which is
based on recently acquired directed- and weighted-connectivity data from tract
tracing experiments, and which incorporates heterogeneity across areas. A
hierarchy of timescales naturally emerges from this system: sensory areas show
brief, transient responses to input (appropriate for sensory processing), whereas
association areas integrate inputs over time and exhibit persistent activity
(suitable for decision-making and working memory). The model displays multiple
temporal hierarchies, as evidenced by contrasting responses to visual versus
somatosensory stimulation. Moreover, slower prefrontal and temporal areas have a
disproportionate impact on global brain dynamics. These findings establish a
circuit mechanism for "temporal receptive windows" that are progressively
enlarged along the cortical hierarchy, suggest an extension of time integration
in decision making from local to large circuits, and should prompt a re
evaluation of the analysis of functional connectivity (measured by fMRI or
electroencephalography/magnetoencephalography) by taking into account inter-areal
heterogeneity.
PMID- 26439532
TI - Many Light Touches Convey the Message.
AB - Our attraction to precision and symmetry in everyday life must be put aside to
appreciate how natural selection favors networks governed by weak interactions,
multivalency, and proteins described as low complexity (LC) and/or intrinsically
disordered (ID). Phosphorylation, ubiquitination, and glycosylation of proteins
often act as weak docking sites for multivalent adaptor proteins in the formation
of membrane-associated and soluble complexes that mediate information flow in
cells. Multiple post-translational modification (PTM) sites together with LC and
ID regions in proteins can mediate phase transition from soluble complexes to
liquid droplets in the cytoplasm or tethering to the membrane. Although
compositionally complex and highly dynamic, these systems display remarkable
control of specificity, timing, and switch-like behavior in signaling pathways.
PMID- 26439531
TI - Microhomology-Mediated End Joining: A Back-up Survival Mechanism or Dedicated
Pathway?
AB - DNA double-strand breaks (DSBs) disrupt the continuity of chromosomes and their
repair by error-free mechanisms is essential to preserve genome integrity.
Microhomology-mediated end joining (MMEJ) is an error-prone repair mechanism that
involves alignment of microhomologous sequences internal to the broken ends
before joining, and is associated with deletions and insertions that mark the
original break site, as well as chromosome translocations. Whether MMEJ has a
physiological role or is simply a back-up repair mechanism is a matter of debate.
Here we review recent findings pertaining to the mechanism of MMEJ and discuss
its role in normal and cancer cells.
PMID- 26439533
TI - Alexander Rich: In Memoriam.
PMID- 26439535
TI - Molecular epidemiological analyses of Cryptosporidium parvum virus 1 (CSpV1), a
symbiotic virus of Cryptosporidium parvum, in Japan.
AB - We show that Cryptosporidium parvum virus 1 (CSpV1), a member of the family
Partitiviridae, genus Cryspovirus that can infect Cryptosporidium parvum, is a
new candidate for high-resolution tool for tracing C. parvum. CSpV1 was detected
in all C. parvum-positive samples tested. Phylogenetic analysis of dsRNA1
sequence from CSpV1 can distinguish infected areas of C. parvum on the national
level. Sequences detected in samples from Iwate prefecture and other islands
(Tanegashima, and Okinawa) belonged to a single clade. This system can
differentiate the samples from Hokkaido and south part of Japan as well as from
other countries. Samples from Iwate, Tanegashima, and Okinawa belonged to a
single subclade, respectively. Therefore, the CSpV1 dsRNA sequences reflect the
regional distribution of their host and have potential as a high-resolution tool
to trace C. parvum IIaA15G2R1 subtype.
PMID- 26439536
TI - Sequential solvent induced phase transition extraction for profiling of
endogenous phytohormones in plants by liquid chromatography-mass spectrometry.
AB - In the current study, a novel method for high-throughput and sensitive
determination of 12 phytohormones in plants was developed by using sequential
solvent induced phase transition extraction (SIPTE) coupled with ultra
performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In
sequential SIPTE, 0.1% formic acid (v/v) and 50mM NaHCO3 aqueous solution were
used for enrichment and purification of alkaline and acidic phytohormones from
the acetonitrile extract of plant tissues in sequence, in which hydrophobic
solvent (toluene) was added to the acetonitrile aqueous mixture for driving the
phase separation. Under optimized sequential SIPTE conditions, the phytohormones
in acetonitrile extract of plant tissues could be effectively enriched and
purified, which was in favor of the following UPLC-MS/MS analysis with less
matrix effect. The phytohormones could be detected using the developed sequential
SIPTE-UPLC-MS/MS method with the limits of the detection (LODs) ranging from 0.56
to 438.60pgmL(-1) and linear range over 2 orders of magnitude with correlation
coefficients (r)>0.9970. The relative recoveries of the detected phytohormones
were in the range of 85.1-114.6%. Finally, the proposed method was applied to
simultaneous determination of endogenous phytohormones in different tissues of
model plants (Oryza sativa and Arabidopsis thaliana) with small amount of sample
size (5mg, fresh weight). The proposed method may be suitable for studying the
distribution of phytohormones in model plants.
PMID- 26439537
TI - Impact of anaemia treatment for left ventricular remodelling prior to initiation
of dialysis in chronic kidney disease patients: Efficacy and stability of long
acting erythropoietin stimulating agents.
AB - AIM: Anaemia is a common complication in patients with chronic kidney disease
(CKD), which may initiate or accelerate left ventricular (LV) hypertrophy (LVH).
The present study is a retrospective analysis to assess whether anaemia treatment
is independently associated with LV remodelling prior to initiation of dialysis
in CKD patients. METHODS: Biochemical and physical values were collected over a
period of more than 120 days prior to the initiation of dialysis in 27 patients
with CKD. The left ventricular mass index (LVMI) was evaluated by
echocardiography twice (at the baseline and the follow-up at the initiation of
the dialysis period). RESULTS: Patients using long-acting erythropoietin
stimulating agents (L-ESA) had the tendency of maintaining higher levels of
haemoglobin (Hb) than those using short-acting ESA (S-ESA). Patients using L-ESA
showed a more significant improvement in the erythropoietin resistance index
(ERI) than those of using S-ESA. In a multivariate regression analysis, the
average Hb level for the observational period, the level of Hb at the initiation
of dialysis and the use of L-ESA were independently associated factors for the
LVMI at the initiation of dialysis. A lower LVMI at the initiation of dialysis
and an improvement of the LVMI during the observational period were detected in
the highest tertile of average Hb (10.4 g/dL). CONCLUSION: Long-acting ESA was
effective and stable when treating anaemia until the start of dialysis. It is
important to treat anaemia for the prevention of LV remodelling in CKD patients.
These findings have some therapeutic implications for treatment strategies for
pre-dialysis patients.
PMID- 26439534
TI - H2S: A Novel Gasotransmitter that Signals by Sulfhydration.
AB - Hydrogen sulfide (H2S) is a member of the growing family of gasotransmitters.
Once regarded as a noxious molecule predominantly present in the atmosphere, H2S
is now known to be synthesized endogenously in mammals. H2S participates in a
myriad of physiological processes ranging from regulation of blood pressure to
neuroprotection. Its chemical nature precludes H2S from being stored in vesicles
and acting on receptor proteins in the fashion of other chemical messengers.
Thus, novel cellular mechanisms have evolved to mediate its effects. This review
focuses on sulfhydration (or persulfidation), which appears to be the principal
post-translational modification elicited by H2S.
PMID- 26439538
TI - Luminescent (N^C^C) Gold(III) Complexes: Stabilized Gold(III) Fluorides.
AB - We report the design, synthesis, and application of a (N^C^C)-ligand framework
able to stabilize highly electron-deprived gold(III) species. This novel platform
enabled the preparation of C(sp(2))-gold(III) fluorides for the first time in
monomeric, easy-to-handle, bench-stable form by a Cl/F ligand-exchange reaction.
Devoid of oxidative conditions or stoichiometric use of toxic Hg salts, this
method was applied to the preparation of multiple [C(sp(2))-Au(III)-F] complexes,
which were used as mechanistic probes for the study of the unique properties and
intrinsic reactivity of Au-F bonds. The improved photophysical properties of
[(N^C^C)Au(III)] complexes compared to classical pincer (C^N^C)-Au systems paves
the way for the design of new late-transition-metal-based OLEDs.
PMID- 26439539
TI - Introduction: The role of shame in psychoanalytic theory and practice.
AB - Introducing three papers by Leon Wurmser, Claude Janin and John Steiner the
author gives an overview of the development of the concept of shame in
psychoanalytic theory and practice. Different aspects of the phenomenon of shame
are being discussed including its relation to guilt, object relations and
identity as well as the role of gaze when emerging from a psychic retreat.
PMID- 26439540
TI - Silencing Nicotiana attenuata LHY and ZTL alters circadian rhythms in flowers.
AB - The rhythmic opening/closing and volatile emissions of flowers are known to
attract pollinators at specific times. That these rhythms are maintained under
constant light or dark conditions suggests a circadian clock involvement.
Although a forward and reverse genetic approach has led to the identification of
core circadian clock components in Arabidopsis thaliana, the involvement of these
clock components in floral rhythms has remained untested, probably because of the
weak diurnal rhythms in A. thaliana flowers. Here, we addressed the role of these
core clock components in the flowers of the wild tobacco Nicotiana attenuata,
whose flowers open at night, emit benzyl acetone (BA) scents and move vertically
through a 140 degrees arc. We first measured N. attenuata floral rhythms under
constant light conditions. The results suggest that the circadian clock controls
flower opening, BA emission and pedicel movement, but not flower closing. We
generated transgenic N. attenuata lines silenced in the homologous genes of
Arabidopsis LATE ELONGATED HYPOCOTYL (LHY) and ZEITLUPE (ZTL), which are known to
be core clock components. Silencing NaLHY and NaZTL strongly altered floral
rhythms in different ways, indicating that conserved clock components in N.
attenuata coordinate these floral rhythms.
PMID- 26439584
TI - Graphene-oxide-supported ultrathin Au nanowires: efficient electrocatalysts for
borohydride oxidation.
AB - We report stable ultrathin Au nanowires supported on reduced graphene oxide with
outstanding electrocatalytic activity for borohydride oxidation. Electrochemical
impedance spectroscopy measurements showed abnormal inductive behavior,
indicative of surface reactivation. DFT calculations indicate that the origin of
the high activity stems from the position of the Au d-band center.
PMID- 26439541
TI - Algorithm for the management of ERCP-related perforations.
AB - BACKGROUND AND AIMS: Perforation is a rare but serious adverse event of ERCP.
There is no consensus to guide the clinician on the management of ERCP-related
perforations, with particular controversy surrounding the immediate surgical
management of postprocedurally detected duodenal perforation because of
overextension of a sphincterotomy. Our aim was to assess patient outcomes using a
predetermined algorithm based on managing ERCP-related duodenal perforations
according to the mechanism of injury. METHODS: A retrospective single-center
study of all consecutive patients with Stapfer type I and II perforations between
2000 and 2014 were included. Our institutional algorithm since 2000 dictated that
Stapfer type I perforations (duodenal wall perforation, endoscope related) should
be managed surgically unless prohibited by underlying comorbidities and Stapfer
type II perforations (periampullary, sphincterotomy related) managed
nonsurgically unless a deterioration in clinical status necessitated surgery.
RESULTS: Sixty-one patients (mean age, 51 years; 80% women) were analyzed with
Stapfer type I perforations diagnosed in 7 (11%) and type II in 54 (89%). A
postprocedural diagnosis of perforation was made in 55 patients (90%). Four
patients (7%) had Stapfer type II perforations that failed medical management and
required surgery. The mean length of stay (LOS) in the entire cohort was 9.6 days
with a low mortality rate of 3%. Systemic inflammatory response syndrome was
observed in 18 patients (33%) with Stapfer type II perforations and was not
associated with the need for surgery. Concurrent post-ERCP pancreatitis was
diagnosed in 26 patients (43%) and was associated with an increased LOS.
CONCLUSIONS: Stapfer type II perforations have excellent outcomes when managed
medically. We validate an algorithm for the management of ERCP-related
perforations and propose that it should function as a guide.
PMID- 26439585
TI - Blood Volume Monitoring to Assist Fluid Management in Hemodialysis Patients.
PMID- 26439586
TI - Fabrication of 2D Heterojunction in Graphene via Low Energy N2(+) Irradiation.
AB - Substitutional doping in graphene is locally induced with very low energy
nitrogen ions. Irradiated and nonirradiated areas exhibit different charge
carrier densities and are separated by a sharp boundary, stable up to 750
degrees C. The way towards lithographic control of the electronic properties of
graphene by ion irradiation is paved, providing a proof of principle for the
fabrication of 2D graphene-based heterojunctions.
PMID- 26439587
TI - Endoneurial edema in sural nerve may indicate recent onset inflammatory
neuropathy.
AB - INTRODUCTION: Sural nerve biopsy is an important means of establishing the
diagnosis of inflammatory neuropathies. We investigated the diagnostic value of
endoneurial edema. METHODS: Diagnostic sural nerve biopsies from 42 patients with
inflammatory and 28 patients with noninflammatory neuropathies were re-evaluated
for the presence of endoneurial edema. Edema was assessed on hematoxylin-eosin
stained paraffin and frozen sections and on azure II-methylene blue stained
semithin sections. We determined the area of endoneurial edema on digitized
images in relation to the entire endoneurial area of each fascicle. RESULTS:
Edema was more extensive in neuropathies with short disease duration (<=12
months) as compared to long duration (>12 months; P < 0.01). Edema in
inflammatory neuropathies of <=12 months duration covered a larger area than in
noninflammatory neuropathies (P < 0.01), and the extent of edema correlated
negatively with disease duration (P < 0.05). CONCLUSIONS: Endoneurial edema may
be a useful additional disease marker in inflammatory neuropathies of recent
onset.
PMID- 26439588
TI - Testing the Assessment of New Radiation Oncology Technology and Treatments
framework using the evaluation of post-prostatectomy radiotherapy techniques.
AB - INTRODUCTION: We tested the ability of the Assessment of New Radiation Oncology
Technology and Treatments framework to determine the clinical efficacy and safety
of intensity-modulated radiation therapy (IMRT) compared with 3-dimensional
radiation therapy (3DCRT) for post-prostatectomy radiation therapy (PPRT) to
support its timely health economic evaluation. METHODS: Treatment plans produced
using FROGG guidelines provided dosimetry parameters for both techniques at 64 Gy
and 70 Gy and were also used to model early and late outcome probabilities.
Clinical parameters were derived from early toxicity and quality of life patient
data, systematic literature review and expert opinion. Dosimetry parameters were
correlated with the measures of clinical efficacy and safety. RESULTS: Data from
two patient cohorts (29 and 27 respectively) were collected within the project
timeframe, providing evidence for acute toxicity and quality of life, and
dosimetric comparisons. Relative rates of tumour control probability (TCP) and
normal tissue control probability (NTCP) modelling were readily derived from the
planning exercise and demonstrated advantages in uncomplicated TCP for IMRT over
3DCRT, predominantly due to normal tissue sparing. The safety of IMRT delivery
was demonstrated with TCP uncompromised by IMRT protocol violations, which
achieved rectal sparing only by reducing minimum target dose and coverage.
CONCLUSION: Sources of desk-top and patient-based evidence were successfully used
to demonstrate potential improved clinical efficacy and safety of applying dose
escalation using IMRT instead of 3DCRT in PPRT.
PMID- 26439589
TI - Direct Catalytic Asymmetric Mannich-Type Reaction of alpha-N3 Amide.
AB - An alpha-N3 7-azaindoline amide serves as a latent enolate to directly engage in
an asymmetric Mannich-type reaction with N-thiophosphinoyl imines by the action
of a cooperative catalyst. The thus-obtained highly enantioenriched anti-adduct
was transformed into beta-amino-alpha-azido acid in high yield by simple acidic
treatment.
PMID- 26439590
TI - Temperature and time variations during osteotomies performed with different
piezosurgical devices: an in vitro study.
AB - AIM: The aim of this experimental in vitro study was to evaluate the effects of
the piezoelectric device in temperature and time variations in standardized
osteotomies performed with similar tip inserts in bovine bone blocks. METHODS:
Two different piezosurgical devices were used the OE-F15((r)) (Osada Inc., Los
Angeles, California, USA) and the Surgybone((r)) (Silfradent Inc., Sofia, Forli
Cesena, Italy). Serrated inserts with similar geometry were coupled with each
device (ST94 insert/test A and P0700 insert/test B). Osteotomies 10 mm long and 3
mm deep were performed in bone blocks resembling type II (dense) and type IV
(soft) bone densities with and without irrigation. Thermal changes and time
variations were recorded. The effects of bone density, irrigation, and device on
temperature changes and time necessary to accomplish the osteotomies were
analyzed. RESULTS: Thermal analysis showed significant higher temperatures during
piezosurgery osteotomies in hard bone without irrigation (P < 0.05). The type of
piezosurgical device did not influence thermal variations (P > 0.05). Time
analysis showed that the mean time values necessary to perform osteotomies were
shorter in soft bone than in dense bone (P < 0.05). CONCLUSIONS: Within the
limitations of this in vitro study, it may be concluded that the temperature
increases more in piezosurgery osteotomies in dense bone without irrigation; the
time to perform the osteotomy with piezosurgery is shorter in soft bone compared
to hard bone; and the piezosurgical device have a minimal influence in the
temperature and time variations when a similar tip design is used during
piezosurgery osteotomies.
PMID- 26439591
TI - Clinical experience of imiquimod 3.75% for actinic keratosis: results from a case
series.
AB - BACKGROUND: In clinical studies, imiquimod 3.75% was shown to detect and treat
actinic keratosis (AK) lesions across an entire sun-exposed field such as the
full face or balding scalp. The aim of this study was to evaluate imiquimod 3.75%
in a real-life clinical setting. METHODS: Ten AK patients applied imiquimod 3.75%
to the full face or scalp once-daily in two 2-week treatment cycles separated by
a two-week treatment-free interval and were followed-up eight weeks later. Seven
patients rated imiquimod 3.75% versus prior treatments (cryotherapy, photodynamic
therapy, diclofenac sodium 3%, imiquimod 5%, ingenol mebutate). RESULTS: The
median clinical lesion count at baseline was 12.5. This increased to a median
Lmax (maximum lesion count during treatment) of 22.5 as imiquimod 3.75% unmasked
previously invisible subclinical lesions. At final follow-up, the median lesion
count was 0. Local skin reactions such as erythema, scabbing and erosion occurred
during each treatment cycle and were easy to manage. All patients considered
imiquimod 3.75% easier to apply than prior treatments and 5 reported fewer or
similar side effects. CONCLUSIONS: In this cohort, imiquimod 3.75% effectively
cleared clinical and subclinical lesions across the entire affected field and was
well tolerated.
PMID- 26439592
TI - Paraneoplastic skin disorders: a review.
AB - Paraneoplastic disorders are manifestations of internal malignancies without the
direct action of the tumor. Its pathogenesis involves production of substances
that interfere with cellular activity of distant tissues. Paraneoplasias may be
the first sign of cancer, and clinicians should be familiarized with its
manifestations in order to perform an early diagnosis of the underlying neoplasm.
The aim of this review was to describe most common paraneoplastic skin diseases.
PMID- 26439593
TI - A new test and graphical tool to assess the goodness of fit of logistic
regression models.
AB - A prognostic model is well calibrated when it accurately predicts event rates.
This is first determined by testing for goodness of fit with the development
dataset. All existing tests and graphic tools designed for the purpose suffer
several drawbacks, related mainly to the subgrouping of observations or to heavy
dependence on arbitrary parameters. We propose a statistical test and a graphical
method to assess the goodness of fit of logistic regression models, obtained
through an extension of similar techniques developed for external validation. We
analytically computed and numerically verified the distribution of the underlying
statistic. Simulations on a set of realistic scenarios show that this test and
the well-known Hosmer-Lemeshow approach have similar type I error rates. The main
advantage of this new approach is that the relationship between model predictions
and outcome rates across the range of probabilities can be represented in the
calibration belt plot, together with its statistical confidence. By readily
spotting any deviations from the perfect fit, this new graphical tool is designed
to identify, during the process of model development, poorly modeled variables
that call for further investigation. This is illustrated through an example based
on real data.
PMID- 26439594
TI - Biomedical applications of high gradient magnetic separation: progress towards
therapeutic haeomofiltration.
AB - High gradient magnetic separation is a well-established technology in the mineral
processing industry, and has been used for decades in the bioprocessing industry.
Less well known is the increasing role that high gradient magnetic separation is
playing in biomedical applications, for both diagnostic and therapeutic purposes.
We review here the state of the art in this emerging field, with a focus on
therapeutic haemofiltration, the key enabling technologies relating to the
functionalisation of magnetic nanoparticles with target-specific binding agents,
and the development of extra-corporeal circuits to enable the in situ filtering
of human blood.
PMID- 26439595
TI - Magnetorelaxometry procedures for quantitative imaging and characterization of
magnetic nanoparticles in biomedical applications.
AB - BACKGROUND: Quantitative knowledge about the spatial distribution and local
environment of magnetic nanoparticles (MNPs) inside an organism is essential for
guidance and improvement of biomedical applications such as magnetic hyperthermia
and magnetic drug targeting. Magnetorelaxometry (MRX) provides such quantitative
information by detecting the magnetic response of MNPs following a fast change in
the applied magnetic field. METHODS: In this article, we review our MRX based
procedures that enable both the characterization and the quantitative imaging of
MNPs in a biomedical environment. RESULTS: MRX characterization supported the
selection of an MNP system with colloidal stability and suitable cellular MNP
uptake. Spatially resolved MRX, a procedure employing multi-channel MRX
measurements allowed for in-vivo monitoring of the MNP distribution in a pre
clinical carcinoma animal model. Extending spatially resolved MRX by consecutive
magnetization of distinct parts of the sample led to a demonstration of MRX
tomography. With this tomography, we reconstructed the three dimensional MNP
distribution inside animal sized phantoms with a sensitivity of milligrams of
MNPs per cm3. In addition, the targeting efficiency of MNPs in whole blood was
assessed using a flow phantom and MRX quantification. CONCLUSION: These MRX based
measurement and analysis procedures have substantially supported the development
of MNP based biomedical applications.
PMID- 26439596
TI - Protective effect of telmisartan treatment against arsenic-induced testicular
toxicity in rats.
AB - Oxidative/nitrosative stress, inflammation, and apoptosis play a crucial role in
the pathogenesis of arsenic-induced testicular injury. Telmisartan, the
angiotensin II-receptor antagonist, possesses antioxidant and anti-inflammatory
activities. The protective effect of telmisartan against arsenic-induced
testicular damage was investigated in rats. Testicular damage was induced by
sodium arsenite (10 mg kg-1/day, p.o., for 2 consecutive days). Telmisartan (10
mg kg-1/day, i.p.) was given for 3 consecutive days, starting 1 day before sodium
arsenite administration. Telmisartan significantly attenuated the arsenic-induced
decrease in the levels of serum testosterone and testicular reduced glutathione,
and significantly decreased the elevation of the levels of testicular
malondialdehyde, nitric oxide, and arsenic levels, as well as myeloperoxidase
activity resulting from sodium arsenite administration. Histopathological and
immunohistochemical examination revealed that telmisartan markedly attenuated
testicular tissue changes, and decreased the arsenic-induced expression of
vascular endothelial growth factor, inducible nitric oxide synthase, tumor
necrosis factor-alpha, cyclooxygenase-2, nuclear factor-kappaB, and caspase-3.
Telmisartan, via its antioxidant and/or anti-inflammatory effects, may represent
a potential candidate to protect against the deleterious effects of arsenic on
testicular tissue.
PMID- 26439597
TI - Inhibition of AKT signaling by supercritical CO2 extract of mango ginger (Curcuma
amada Roxb.) in human glioblastoma cells.
AB - BACKGROUND: Mango ginger (Curcuma amada Roxb.) is a less-investigated herb for
anticancer properties than other related Curcuma species. AKT (a serine/threonine
protein kinase B, originally identified as an oncogene in the transforming
retrovirus AKT8) plays a central role in the development and promotion of cancer.
In this investigation, we have analyzed the effect of supercritical CO2 extract
of mango ginger (CA) on the genetic pathways associated with AKT signaling in
human glioblastoma cells. METHODS: The inhibitory effect of supercritical CO2
extract of mango ginger (Curcuma amada) on AKT signaling was investigated in U
87MG glioblastoma cells. RESULTS: CA was highly cytotoxic to glioblastoma cell
line (IC50=4.92+/-0.81 ug/mL) compared to mHypoE-N1 normal mouse hypothalamus
cell line (IC50=40.57+/-0.06 ug/mL). CA inhibits AKT (protein Kinase B) and
adenosine monophophate -activated protein kinase alpha (AMPKalpha)
phosphorylation significantly in a dose-dependent manner. The cell migration
which is necessary for invasion and metastasis was also inhibited by CA
treatment, with about 43% reduction at 20 ug/mL concentration. Analysis of mRNA
and protein expression of genes associated with apoptosis, cell proliferation and
angiogenesis showed that CA modulates expression of genes associated with
apoptosis (Bax, Bcl-2, Bcl-X, BNIP3, caspase-3, mutant p53 and p21), cell
proliferation (Ki67) and angiogenesis vascular endothelial growth factor (VEGF).
Additionally, heat shock protein 90 (HSP90) and AMPKalpha genes interacting with
the AKT signaling pathway were also downregulated by CA treatment. CONCLUSIONS:
These results indicate the molecular targets and mechanisms underlying the
anticancer effect of CA in human glioblastoma cells.
PMID- 26439598
TI - Investigation of Mixed Surfactant Films at Water Surface Using Molecular Dynamics
Simulations.
AB - Multicomponent Langmuir monolayers are important models of organic coatings of
naturally occurring water-vapor interfaces such as the surfaces of oceans or
aerosol particles. We investigated mixed monolayers comprised of palmitic acid,
C15H31COOH (PA) and 1-bromoalkanes of different chain length (C5, C10, and C16)
at the air-water interface employing classical molecular dynamics simulations.
Different composition ratios and lateral compression of the monolayers were
considered. The structural parameters, such as density profiles, and deuterium
order parameter, evaluated as functions of composition and the lateral film
packing, provide microscopic information about organization and dynamics of the
mixed monolayers. Simulations demonstrate that stable and well mixed monolayers
are formed by the mixtures of PA and BrC16H33 (BrCl6), whereas the two considered
shorter bromoalkanes, BrC5H11 (BrC5) and BrC10H21 (BrC10), do not form stable
films. This is in accord with earlier experimental studies. Under high lateral
pressures, in PA/BrC10 mixed systems molecules of the bromoalkane readily flip in
the monolayer and subsequently leave the film, while the molecules of the longer
BrC16 are expelled from the PA film but no flipping occurs. These results suggest
that the film collapse under pressure is preceded by squeezing-out of
bromoalkanes from the PA monolayer.
PMID- 26439599
TI - Pharmacotherapeutic options for treating brain metastases in non-small cell lung
cancer.
AB - INTRODUCTION: Central nervous system (CNS) metastases represent an important
cause of morbidity and mortality in non-small cell lung cancer (NSCLC) patients.
Local approaches of neurosurgery (usually for single brain lesions), whole brain
radiotherapy, and stereotactic radiosurgery are often withheld for the treatment
of NSCLC-derived brain metastases (BMs). However, systemic treatment is
consistently emerging as an option for patients with asymptomatic BMs, which
could allow for delaying cranial radiotherapy at symptomatic/radiological
progression. AREAS COVERED: Chemotherapy, monoclonal antibodies, tyrosine-kinase
inhibitors (TKIs) for molecularly selected NSCLCs, such as epidermal growth
factor receptor (EGFR)-mutant and anaplastic lymphoma kinase (ALK)-rearranged
diseases, and immune checkpoint inhibitors are all systemic treatments that have
shown activity against NSCLC-derived CNS metastases. Among these, EGFR- and ALK
TKIs will be discussed more in detail owing to their superior efficacy in this
context. EXPERT OPINION: Up-front systemic treatment should be considered for
patients with asymptomatic, multiple BMs, as recently acknowledged by the
European Society of Medical Oncology guidelines. Nevertheless, it must be
emphasized that the best treatment strategy for NSCLC-derived BMs has to be
defined within a multidisciplinary team.
PMID- 26439600
TI - Novel POSS-PCU Nanocomposite Material as a Biocompatible Coating for Quantum
Dots.
AB - Quantum dots (QDs) are fluorescent nanoparticles with unique photophysical
properties that enable them to potentially replace traditional organic dyes and
fluorescent proteins in various bioimaging applications. However, the inherent
toxicity of their cores based on cadmium salts limits their widespread biomedical
use. We have developed a novel nanocomposite polymer emulsion based on polyhedral
oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) that can be
used to coat quantum dots to nullify their toxicity and enhance photostability.
Here we report the synthesis and characterization of a novel POSS-PCU
nanocomposite polymer emulsion and describe its application for coating QDs for
biological application. The polymer was synthesized by a process of emulsion
polymerization and formed stable micelles of ~33 nm in diameter. CdTe/CdS/ZnS QDs
were efficiently stabilized by the polymer emulsion through encapsulation within
the polymer micelles. Characterization studies showed no significant change in
the unique photophysical properties of QDs after coating. The polymer was
biocompatible to HepG2, HUVECs, and mouse skeletal muscle cells at 2.5% after 24
h exposure on in vitro testing. Polymer encapsulated QDs showed enhanced
photostability on exposure to high degrees of UV irradiation and air as well as
significantly reduced cytotoxicity on exposure to HepG2 cells at 30 MUg/mL for 24
h. We have therefore concluded that the POSS-PCU polymer emulsion has the
potential to make a biocompatible and photostable coating for QDs enabling a host
of biomedical applications to take this technology to the next level.
PMID- 26439601
TI - Engaging communities to improve mental health in African and African Caribbean
groups: a qualitative study evaluating the role of community well-being
champions.
AB - Over the last decade, Britain has undergone reforms to promote engagement in
local structures of governance. These reforms have encouraged the promotion of
active citizenship and have been central to the government's public service
modernisation agenda. This article presents the findings from a study evaluating
a pilot outreach intervention which adopted a community engagement model to
address the mental health needs of African and African Caribbean groups, which
entailed a partnership between faith-based organisations, local public services
and community organisations to co-produce the pilot project. Lay people were
trained to raise awareness about mental health among these communities in South
London. Between 2012 and 2013, a qualitative participatory approach was used to
evaluate the pilot project, which enabled a researcher to take part in the
engagement phase of the pilot project, and the project co-ordinators to be
involved in the research process. Semi-structured, one-to-one interviews were
carried out with 13 community and well-being champions (CWBCs) recruited from
African and African Caribbean communities (seven male and six female). This study
examines the impact of the relationship between the intervention and community
through the participants' engagement in the pilot outreach project and the action
undertaken as champions. We found that although CWBCs used circles of influence
to share ideas about mental health and well-being and to encourage change, they
encountered resistance on the part of the people they engaged with, which
resulted from a lack of knowledge about mental health, taboos and ascribed
stigma. We argue that CWBCs acted as healthy examples to communicate mental
health knowledge to those approached, but that they needed to be equipped with
bespoke communication skills to be able to talk about such sensitive issues as
mental health.
PMID- 26439602
TI - "When we are together I feel at home." Types and sources of social support among
youth newly diagnosed with HIV in Kenya: implications for intervention.
AB - Social support helps youth manage psychosocial stress. Though many studies have
investigated the role of social support in helping youth in developed countries
cope with their HIV status, such research is lacking among youth living in sub
Saharan African countries, including Kenya. The importance of research on youth
living with HIV in Kenya is enhanced given young people's unique developmental
stages and the HIV prevalence rate of 8.8% among Kenyans aged 25 to 29 years. To
gain further insight, qualitative focus group interviews were conducted with 53
youth aged 18 to 27 years who lived in the informal urban settlement of Kibera in
Nairobi, Kenya. A phenomenological approach was used to analyse the data from
which four major types of social support were identified: 1) emotional; 2)
informational; 3) appraisal; and 4) instrumental. Within each of these
overarching themes more specific sub-themes were identified. The youth also
reported receiving social support from eight main sources: 1) family; 2) friends;
3) clinicians and clinical services; 4) counsellors; 5) support groups; 6)
religious sources; 7) partners; and 8) other. These findings suggest that various
forms of social support, provided by diverse sources, which may fall outside of
those commonly involved in interventions, can help youth living with HIV cope
with their diagnosis and promote healthy lifestyles. Future research should
investigate the roles and interactions of different types and sources of support,
specifically as they relate to interventions aiming to ameliorate the experiences
of youth newly diagnosed with HIV.
PMID- 26439603
TI - HIV-related disabilities: an extra burden to HIV and AIDS healthcare workers?
AB - BACKGROUND: Healthcare workers have been at the forefront of dealing with the
impact of HIV and AIDS at all stages of the pandemic. This brings new challenges
to include disability into HIV care. However, the implications for healthcare
workers in an already fragile health system along with HIV-related disabilities
in persons living with HIV are little understood. This study examined the
healthcare workers' perspective on disability in HIV care. METHOD: This article
describes a qualitative study using in-depth interviews with 10 healthcare
workers in a semi-urban hospital setting in KwaZulu-Natal, South Africa. The
study aimed to understand healthcare workers' experiences with disability in the
context of HIV. The International Classification of Functioning Disability and
Health (ICF) was used as a guiding framework to understand disability. RESULTS:
Healthcare workers described HIV-related disabilities on all three levels of
disability, namely impairments/ body function, activity limitations and
participation restrictions, as affecting the livelihood of their patients and
household members. Issues also arose from disability and stigma that were
perceived as affecting adherence to antiretroviral treatment. In addition,
healthcare workers encounter challenges in dealing with the increased needs of
care and support for those people living with HIV who experience HIV-related
disabilities. They indicated a limited ability to cope and respond to these
needs. Primarily they arrange additional referrals to manage complex or episodic
disabilities. Participants also identified issues such as excessive work load,
lack of resources and training and emotional challenges in dealing with
disability. CONCLUSION: Healthcare workers need support to respond to the
increased needs of people living with HIV who have HIV-related disabilities.
Responses need to reflect: 1) increase in rehabilitative staff including in
community outreach programmes; 2) skills training in HIV-related disability; and
3) psychosocial support for healthcare workers.
PMID- 26439604
TI - Vanadium Nitride Nanowire Supported SnS2 Nanosheets with High Reversible Capacity
as Anode Material for Lithium Ion Batteries.
AB - The vulnerable restacking problem of tin disulfide (SnS2) usually leads to poor
initial reversible capacity and poor cyclic stability, which hinders its
practical application as lithium ion battery anode (LIB). In this work, we
demonstrated an effective strategy to improve the first reversible capacity and
lithium storage properties of SnS2 by growing SnS2 nanosheets on porous flexible
vanadium nitride (VN) substrates. When evaluating lithium-storage properties, the
three-dimensional (3D) porous VN coated SnS2 nanosheets (denoted as CC-VN@SnS2)
yield a high reversible capacity of 75% with high specific capacity of about 819
mAh g(-1) at a current density of 0.65 A g(-1). Remarkable cyclic stability
capacity of 791 mAh g(-1) after 100 cycles with excellent capacity retention of
97% was also achieved. Furthermore, discharge capacity as high as 349 mAh g(-1)
is still retained after 70 cycles even at a elevated current density of 13 A g(
1). The excellent performance was due to the conductive flexible VN substrate
support, which provides short Li-ion and electron pathways, accommodates large
volume variation, contributes to the capacity, and provides mechanical stability,
which allows the electrode to maintain its structural stability.
PMID- 26439605
TI - Extending the reservoir of bla IMP-5: the emerging pathogen Acinetobacter
bereziniae.
AB - AIM: Acinetobacter bereziniae clinical relevance is starting to be recognized;
however, very few descriptions of its carbapenem resistance currently exist. Here
we characterize two carbapenem-resistant A. bereziniae isolates. MATERIALS &
METHODS: Isolates were obtained from environmental and clinical samples.
Carbapenemases were searched by phenotypic, biochemical and PCR assays. Clonality
was studied by ApaI-PFGE and genetic location for carbapenemase genes were
assessed by I-CeuI and S1 hybridizations. RESULTS: Isolates were not clonally
related but both produced the 'exclusively Portuguese' IMP-5, with the clinical
isolate also producing an OXA-58. The carbapenemase genes were plasmid located.
CONCLUSION: Our results emphasize the role of non-baumannii Acinetobacter species
as important reservoirs of clinically relevant resistance genes that could also
contribute to their emergence as nosocomial pathogens.
PMID- 26439606
TI - Interplay between Open-Shell Character, Aromaticity, and Second
Hyperpolarizabilities in Indenofluorenes.
AB - Focusing on the original and extended indenofluorene frameworks, we theoretically
investigate the interplay between the open-shell character, the aromaticity, and
the second hyperpolarizabilities gamma. Interestingly, the odd-electron density
distribution, which illustrates the spatial contribution of the open-shell
character, is found to well correlate with the magnetic shielding tensor
distribution, which indicates the magnetic criteria of the aromaticity. This can
be explained with the partial destruction of the pi-delocalization due to the
emergence of odd (unpaired) electrons. Further investigation on the gamma values,
which are third-order nonlinear optical (NLO) properties at the molecular scale,
reveals the correlation of strong enhancement of gamma and its density
distribution to the intermediate open-shell character and its odd-electron
density distribution. These results will contribute not only to the detailed
understanding of the structure-NLO property relationships in the indenofluorene
frameworks but also to building new design guidelines for highly efficient NLO
molecules based on the open-shell character-aromaticity correlation.
PMID- 26439607
TI - Utility of checklist to describe experimental methods for investigating molecular
biomarkers.
AB - INTRODUCTION: In research articles, detailed description of experimental methods
and reagents is fundamental for correct reproducibility of the published data.
This becomes even more important when such data contribute to identify molecular
targets and toxicity biomarkers whose role is crucial in the physiology and
pathology of human health. Methods & Objectives: To achieve good reproducibility
of data we took advantage of others' experiences and analyzed molecular biology
and immunodetection techniques in 32 journal articles investigating the human
NRF2 and Keap1 genes involved in the cell response to oxidative stress. RESULTS &
CONCLUSIONS: In conclusion of the analysis, we assessed deficiency of information
in the published methods, making it difficult to select appropriate protocols.
Underlining the importance of assay reproducibility, this paper proposes the
utility of a minimum information checklist of methods for biomarker detection.
PMID- 26439608
TI - N-Heterocyclic Carbene-Catalyzed Activation of Esters of N-Hydroxyphthalimide: A
Highly Enantioselective Route to Chiral Dihydropyridinones Bearing an All Carbon
Quaternary Stereogenic Center.
AB - An N-heterocyclic carbene-catalyzed highly enantioselective [3 + 3] annulation
reaction of N-hydroxyphthalimide (NHPI) 3,3-disubstituted acrylates and N-Ts
ketimines was developed. In most cases, the desired chiral dihydropyridinone
products bearing an all carbon quaternary stereogenic center could be obtained in
good yields with excellent enantioselectivities (>99% ee's), which demonstrated
the NHPI acrylates as a kind of excellent substrate in NHC-catalysis.
PMID- 26439609
TI - A systematic examination of the nature and content of vignettes in schizophrenia
research.
AB - BACKGROUND: Vignettes are often used in psychiatric research, yet there are few
systematic studies on their content, creation, and use. AIMS: This article
describes a study of: (a) how researchers create vignettes in research on
schizophrenia and (b) how these vignettes portray individuals with schizophrenia.
METHOD: We conducted a systematic search of the PubMed database for articles
between 2008 and 2012 that used vignettes to measure attitudes about
schizophrenia. We analyzed the identified vignettes using a tool developed in
reference to DSM criteria. RESULTS: Within the vignettes, 98% of individuals
portrayed demonstrated delusions, 91% demonstrated hallucinations and 29%
demonstrated disorganized speech. The majority of vignettes portrayed individuals
under 25 years and when both genders were not depicted, researchers chose to
depict men much more frequently than women (41% vs. 8%). A majority of articles
did not use original vignettes (55%), and many of the articles (53%) contained
vignettes created by one team of researchers. Most vignettes did not include
positive language or recovery-oriented information. CONCLUSIONS: This study
highlights a need for critical thought on vignette development and utilization,
especially as psychiatry is now moving towards a recovery-based understanding of
mental illness.
PMID- 26439610
TI - Percutaneous central venous catheters versus peripheral cannulae for delivery of
parenteral nutrition in neonates.
AB - BACKGROUND: Neonatal parenteral nutrition may be delivered via peripheral
cannulas or central venous catheters (umbilical or percutaneous). As the result
of complications associated with umbilical catheters, many neonatal units prefer
to use percutaneous catheters after initial stabilisation. Although they can be
difficult to place, these catheters may be more stable than peripheral cannulae
and require less frequent replacement. These delivery methods may be associated
with different risks of adverse events, including acquired invasive infection and
extravasation injury. OBJECTIVES: To determine the effects of infusion of
parenteral nutrition via percutaneous central venous catheters versus peripheral
cannulae on nutrient input, growth and development and complications among
hospitalised neonates receiving parenteral nutrition in terms of adverse
consequences such as bacteraemia or invasive fungal infection, cardiac tamponade
or other extravasation injuries. SEARCH METHODS: We searched the Cochrane Central
Register of Controlled Trials (CENTRAL; 2015, Issue 5), MEDLINE (1966 to June
2015) and EMBASE (1980 to June 2015), as well as conference proceedings and
previous reviews. SELECTION CRITERIA: Randomised controlled trials that compared
delivery of intravenous fluids (primarily parenteral nutrition) via percutaneous
central venous catheters versus peripheral cannulae in hospitalised neonates.
DATA COLLECTION AND ANALYSIS: We extracted data using standard methods of the
Cochrane Neonatal Group, with separate evaluation of trial quality and data
extraction by two review authors. MAIN RESULTS: We found six trials recruiting a
total of 549 infants. One trial showed that use of a percutaneous central venous
catheter was associated with a smaller deficit between prescribed and actual
nutrient intake during the trial period (mean difference (MD) -7.1%, 95%
confidence interval (CI) -11.02 to -3.2). Infants in the percutaneous central
venous catheter group needed significantly fewer catheters/cannulae (MD -4.3, 95%
CI -5.24, -3.43). Meta-analysis of data from all trials revealed no evidence of
an effect on the incidence of invasive infection (typical risk ratio (RR) 0.95,
95% CI 0.72 to 1.25; typical risk difference (RD) -0.01, 95% CI -0.08 to 0.06).
AUTHORS' CONCLUSIONS: Data from one small trial suggest that use of percutaneous
central venous catheters to deliver parenteral nutrition increases nutrient
input. The significance of this in relation to long-term growth and developmental
outcomes is unclear. Three trials suggest that use of percutaneous central venous
catheters decreases the number of catheters/cannulae needed to deliver nutrition.
No evidence suggests that percutaneous central venous catheter use increases
risks of adverse events, particularly invasive infection, although none of the
included trials was large enough to rule out an effect on uncommon severe adverse
events such as pericardial effusion.
PMID- 26439611
TI - Preclinical antitoxic properties of Spirulina (Arthrospira).
AB - CONTEXT: Spirulina (Arthrospira) exerts a wide spectrum of pharmacological
activities which are mainly attributed to its antioxidant effect. However,
Spirulina has also been reported (both in preclinical and in clinical scenarios)
to exhibit other bioactive effects, including an antitoxic potential. OBJECTIVE:
We performed a systematic review of the literature, conducted in TOXNET,
PubMed/MEDLINE, and Science Direct-Scopus; all available years were included.
Searching criteria included the effects of Spirulina on experimental poisonings
from arsenic, cadmium, carbon tetrachloride, deltamethrin, fluoride,
hexachlorocyclohexane, iron, lead, lindane, and mercury. RESULTS: In all cases,
it was established that the blue-green alga, and its isolated compounds,
effectively counteracted these pollutants toxic effects on the exposed organisms.
Some molecular mechanisms are proposed, although they have not been fully
elucidated yet. CONCLUSION: Spirulina could be a useful coadjuvant agent within
clinical practice for treatment of these or other pollutants poisonings.
PMID- 26439612
TI - Sexual Assault Experienced by Deaf Female Undergraduates: Prevalence and
Characteristics.
AB - Approximately 25% of hearing women in the United States experience rape in their
life-time, whereas deaf women have been found to experience increased rates of
assault consistent with other marginalized populations. This study explored
sexual assault prevalence and characteristics of assault in deaf female
undergraduate students. Results revealed that more than two-thirds of the
participants (69%) endorsed experiencing at least one assault and more than half
(56%) experienced multiple types of assault. Most assaults were committed by a
man known to the survivor. Characteristics (e.g., hearing status, primary
language, and ethnicity) of the survivors and the assailants are explored. The
implications of this data are discussed as well as the development of culturally
and linguistically sensitive outreach and educational programs.
PMID- 26439613
TI - Paternal history of diabetes mellitus and hypertension affects the prevalence and
phenotype of PCOS.
AB - PURPOSE: The purpose of the present study is to determine if paternal or maternal
history of diabetes mellitus (DM) and hypertension (HT) contributes to the
prevalence and phenotype of polycystic ovary syndrome (PCOS). METHODS: We
performed an epidemiologic study about PCOS from four districts in Beijing,
China, between 2008 and 2009. Parental histories of DM and HT were collected, and
the basic characteristics and serum indices of 123 PCOS patients and 718 non-PCOS
controls were tested. RESULTS: The prevalence of a parental history of DM and HT
was significantly higher in PCOS patients than non-PCOS women (17.1 % vs. 9.2 %
and 42.3 % vs. 26.0 %, P < 0.05, respectively). When paternal history was
separated from maternal history, only a paternal history of DM and HT reached
statistical significance between PCOS and non-PCOS patients (odds ratio (OR) =
3.42, 95 % confidence interval (CI) = 1.69-6.91; OR = 2.50, 95 % CI = 1.58-3.93,
respectively). A paternal history of both DM and HT was significantly associated
with sex hormone-binding globulin, fasting plasma glucose, and fasting insulin
levels, the free androgen index, and the homeostatic model assessment-insulin
resistance in PCOS patients (P < 0.05 for all). There was no independent
association between maternal history and the clinical or biochemical phenotype of
PCOS. CONCLUSIONS: PCOS patients with a positive paternal history of both DM and
HT have an adverse endocrine and metabolic profile. A paternal history of DM and
HT poses a risk to PCOS.
PMID- 26439616
TI - Generation of remote adaptive torsional shear waves with an octagonal phased
array to enhance displacements and reduce variability of shear wave speeds:
comparison with quasi-plane shear wavefronts.
AB - A method based on adaptive torsional shear waves (ATSW) is proposed to overcome
the strong attenuation of shear waves generated by a radiation force in dynamic
elastography. During the inward propagation of ATSW, the magnitude of
displacements is enhanced due to the convergence of shear waves and constructive
interferences. The proposed method consists in generating ATSW fields from the
combination of quasi-plane shear wavefronts by considering a linear superposition
of displacement maps. Adaptive torsional shear waves were experimentally
generated in homogeneous and heterogeneous tissue mimicking phantoms, and
compared to quasi-plane shear wave propagations. Results demonstrated that
displacement magnitudes by ATSW could be up to 3 times higher than those obtained
with quasi-plane shear waves, that the variability of shear wave speeds was
reduced, and that the signal-to-noise ratio of displacements was improved. It was
also observed that ATSW could cause mechanical inclusions to resonate in
heterogeneous phantoms, which further increased the displacement contrast between
the inclusion and the surrounding medium. This method opens a way for the
development of new noninvasive tissue characterization strategies based on ATSW
in the framework of our previously reported shear wave induced resonance
elastography (SWIRE) method proposed for breast cancer diagnosis.
PMID- 26439615
TI - Structural characterization of amphiphilic siderophores produced by a soda lake
isolate, Halomonas sp. SL01, reveals cysteine-, phenylalanine- and proline
containing head groups.
AB - Soap Lake, located in Washington State, is a naturally occurring saline and
alkaline lake. Several organisms inhabiting this lake have been identified as
producers of siderophores that are unique in structure. Bacterial isolates,
enriched from Soap Lake sediment and water samples, were screened for siderophore
production using both the chrome azurol S (CAS) agar plate and liquid methods.
Bacterial isolate Halomonas sp. SL01 was found to produce relatively high
concentrations of siderophores in liquid medium (up to 40 uM). Siderophores from
the isolate were separated from the culture supernatant using solid phase
extraction and purified by high-performance liquid chromatography (HPLC).
Siderophore structure was determined using LC/MS/MS (liquid chromatography/mass
spectrometry/mass spectrometry) and fatty acid methyl ester (FAME) GC. Two
distinct new families of amphiphilic siderophores were produced by isolate SL01.
All siderophores ranged in size from 989 to 1096 atomic mass units and consisted
of a conserved peptidic head group (per family), which coordinates iron, coupled
to fatty acid moieties. The fatty acyl moieties were C10-C14 in length and some
with hydroxyl substitutions at the third alpha position. These siderophores
resembled amphiphilic aquachelin siderophores produced by Halomonas aquamarina
strain DS40M3, a marine bacterium as well as siderophores from isolate Halomonas
sp. SL28 that was found to produce amphiphilic siderophores. Bacteria thriving
under saline and alkaline conditions are capable of producing unique siderophores
resembling those produced by microbes inhabiting marine environments.
PMID- 26439617
TI - Large-Area Growth of Uniform Single-Layer MoS2 Thin Films by Chemical Vapor
Deposition.
AB - We report the largest-size thin films of uniform single-layer MoS2 on sapphire
substrates grown by chemical vapor deposition based on the reaction of gaseous
MoO3 and S evaporated from solid sources. The as-grown thin films of single-layer
MoS2 were continuous and uniform in thickness for more than 4 cm without the
existence of triangular-shaped MoS2 clusters. Compared to mechanically exfoliated
crystals, the as-grown single-layer MoS2 thin films possessed consistent chemical
valence states and crystal structure along with strong photoluminescence emission
and optical absorbance at high energy. These results demonstrate that it is
possible to scale up the growth of uniform single-layer MoS2 thin films,
providing potentially important implications on realizing high-performance MoS2
devices.
PMID- 26439618
TI - Analysis of Critical Dimensions for Nanowire Core-Multishell Heterostructures.
AB - Critical dimensions for nanowire core-multishell heterostructures are analyzed by
using finite-element method based on the energy equilibrium criteria. Results
show that the nanowire core-shell heterostructure can sufficiently reduce the
strain in the shell and increase the critical shell thickness. The critical
dimensions for the nanowire core-multishell heterostructure are determined by the
stress fields generated at two heterointerfaces. For thin barrier, the critical
dimensions decrease as the core radius increases, while when the barrier is thick
enough, the critical dimensions show an increase with the increase of core radius
conversely. This can be attributed to a competition between the lattice mismatch
and strain distribution, which dominate the critical dimensions alternatively.
Two critical quantum well thicknesses are obtained in the nanowire core
multishell heterostructure. Below the dislocation-free critical thickness, the
structure will be coherent regardless of the barrier thickness. While above the
dislocation-unavoidable thickness, dislocations are always energetically favored.
In the dislocation-controllable region between the two critical thicknesses,
coherent structure can be obtained via controlling the well and barrier
thicknesses. The results are in good agreement with the experimental data and may
serve as guidance for the design of coherent nanowire core-multishell quantum
well structures and devices.
PMID- 26439619
TI - Electromagnetic Enhancement of Graphene Raman Spectroscopy by Ordered and Size
Tunable Au Nanostructures.
AB - The size-controllable and ordered Au nanostructures were achieved by applying the
self-assembled monolayer of polystyrene microspheres. Few-layer graphene was
transferred directly on top of Au nanostructures, and the coupling between
graphene and the localized surface plasmons (LSPs) of Au was investigated. We
found that the LSP resonance spectra of ordered Au exhibited a redshift of ~20 nm
and broadening simultaneously by the presence of graphene. Meanwhile, the surface
enhanced Raman spectroscopy (SERS) of graphene was distinctly observed; both the
graphene G and 2D peaks increased induced by local electric fields of plasmonic
Au nanostructures, and the enhancement factor of graphene increased with the
particle size, which can be ascribed to the plasmonic coupling between the
ordered Au LSPs and graphene.
PMID- 26439620
TI - Neuroendocrine tumor G3: a pancreatic well-differentiated neuroendocrine tumor
with a high proliferative rate.
AB - A 68-year-old man was referred to our hospital because of left upper quadrant
pain. Contrast enhanced computed tomography showed a low density mass with
delayed contrast effects as well as para-aortic node swelling with homogenous
contrast effects. Histological examination of specimens obtained by endoscopic
ultrasound fine needle aspiration revealed a pancreatic neuroendocrine tumor
(NET) G2, according to the World Health Organization 2010 classification, and
lymph node metastasis. Distal pancreatectomy and lymph node dissection were
performed. On histological examination, the tumor showed well-differentiated
morphology with an organoid pattern. The Ki67 labeling index was 21.6 %, and the
mitotic count was 25/10 high power fields. As mentioned above, we made a final
diagnosis of the lesion as "NET G3," because the tumor presented with well
differentiated morphology. Chemotherapy with Everolimus was administered. Liver
metastasis occurred 11 months after the first operation, and a partial
hepatectomy was performed. Histological findings were similar to those of the
first operation. Herein we present a case of pancreatic well-differentiated
neuroendocrine tumor with a high proliferative rate referred to as "NET G3," and
review the relevant literature.
PMID- 26439621
TI - FLCN and AMPK Confer Resistance to Hyperosmotic Stress via Remodeling of Glycogen
Stores.
AB - Mechanisms of adaptation to environmental changes in osmolarity are fundamental
for cellular and organismal survival. Here we identify a novel osmotic stress
resistance pathway in Caenorhabditis elegans (C. elegans), which is dependent on
the metabolic master regulator 5'-AMP-activated protein kinase (AMPK) and its
negative regulator Folliculin (FLCN). FLCN-1 is the nematode ortholog of the
tumor suppressor FLCN, responsible for the Birt-Hogg-Dube (BHD) tumor syndrome.
We show that flcn-1 mutants exhibit increased resistance to hyperosmotic stress
via constitutive AMPK-dependent accumulation of glycogen reserves. Upon
hyperosmotic stress exposure, glycogen stores are rapidly degraded, leading to a
significant accumulation of the organic osmolyte glycerol through transcriptional
upregulation of glycerol-3-phosphate dehydrogenase enzymes (gpdh-1 and gpdh-2).
Importantly, the hyperosmotic stress resistance in flcn-1 mutant and wild-type
animals is strongly suppressed by loss of AMPK, glycogen synthase, glycogen
phosphorylase, or simultaneous loss of gpdh-1 and gpdh-2 enzymes. Our studies
show for the first time that animals normally exhibit AMPK-dependent glycogen
stores, which can be utilized for rapid adaptation to either energy stress or
hyperosmotic stress. Importantly, we show that glycogen accumulates in kidneys
from mice lacking FLCN and in renal tumors from a BHD patient. Our findings
suggest a dual role for glycogen, acting as a reservoir for energy supply and
osmolyte production, and both processes might be supporting tumorigenesis.
PMID- 26439622
TI - Combined Treatment with Exendin-4 and Metformin Attenuates Prostate Cancer
Growth.
AB - INTRODUCTION: Recently, the pleiotropic benefits of incretin-based therapy have
been reported. We have previously reported that Exendin-4, a glucagon-like
peptide-1 (GLP-1) receptor agonist, attenuates prostate cancer growth. Metformin
is known for its anti-cancer effect. Here, we examined the anti-cancer effect of
Exendin-4 and metformin using a prostate cancer model. METHODS: Prostate cancer
cells were treated with Exendin-4 and/or metformin. Cell proliferation was
quantified by growth curves and 5-bromo-2'-deoxyuridine (BrdU) assay. TUNEL assay
and AMP-activated protein kinase (AMPK) phosphorylation were examined in LNCaP
cells. For in vivo experiments, LNCaP cells were transplanted subcutaneously into
the flank region of athymic mice, which were then treated with Exendin-4 and/or
metformin. TUNEL assay and immunohistochemistry were performed on tumors.
RESULTS: Exendin-4 and metformin additively decreased the growth curve, but not
the migration, of prostate cancer cells. The BrdU assay revealed that both
Exendin-4 and metformin significantly decreased prostate cancer cell
proliferation. Furthermore, metformin, but not Exendin-4, activated AMPK and
induced apoptosis in LNCaP cells. The anti-proliferative effect of metformin was
abolished by inhibition or knock down of AMPK. In vivo, Exendin-4 and metformin
significantly decreased tumor size, and further significant tumor size reduction
was observed after combined treatment. Immunohistochemistry on tumors revealed
that the P504S and Ki67 expression decreased by Exendin-4 and/or metformin, and
that metformin increased phospho-AMPK expression and the apoptotic cell number.
CONCLUSION: These data suggest that Exendin-4 and metformin attenuated prostate
cancer growth by inhibiting proliferation, and that metformin inhibited
proliferation by inducing apoptosis. Combined treatment with Exendin-4 and
metformin attenuated prostate cancer growth more than separate treatments.
PMID- 26439623
TI - Development of a brachytherapy audit checklist tool.
AB - PURPOSE: To develop a brachytherapy audit checklist that could be used to prepare
for Nuclear Regulatory Commission or agreement state inspections, to aid in
readiness for a practice accreditation visit, or to be used as an annual internal
audit tool. METHODS AND MATERIALS: Six board-certified medical physicists and one
radiation oncologist conducted a thorough review of brachytherapy-related
literature and practice guidelines published by professional organizations and
federal regulations. The team members worked at two facilities that are part of a
large, academic health care center. Checklist items were given a score based on
their judged importance. Four clinical sites performed an audit of their program
using the checklist. The sites were asked to score each item based on a defined
severity scale for their noncompliance, and final audit scores were tallied by
summing the products of importance score and severity score for each item.
RESULTS: The final audit checklist, which is available online, contains 83 items.
The audit scores from the beta sites ranged from 17 to 71 (out of 690) and
identified a total of 7-16 noncompliance items. The total time to conduct the
audit ranged from 1.5 to 5 hours. CONCLUSIONS: A comprehensive audit checklist
was developed which can be implemented by any facility that wishes to perform a
program audit in support of their own brachytherapy program. The checklist is
designed to allow users to identify areas of noncompliance and to prioritize how
these items are addressed to minimize deviations from nationally-recognized
standards.
PMID- 26439624
TI - Structure study of a microemulsion system with an ionic liquid.
AB - We found that an ionic liquid (IL) with a long alkyl chain moiety, 1-tetradecyl-3
methylimidazolium chloride (C14MIM.Cl), forms a single crystal after the addition
of octanol in an alkane solvent. But the solution exhibits a structural change
after adding a small amount of water. An optically clear solution is found within
limits, and it is stable for several months. Since the IL molecule has an
amphiphilic property, it behaves as a surfactant in the microemulsion system. But
the IL formed a single crystal rather than a lyotropic liquid crystalline
structure, unlike a typical surfactant. Therefore, it is important to understand
the structure of the microemulsion system. We used the small angle neutron
scattering (SANS) technique to investigate the structure. The scattering
intensity was analyzed using a spherical core-shell model with the Schultz size
distribution, and a contrast matching method was used to study the internal
structure. The structure of the solution is confirmed to be a water-in-oil
microemulsion system, and the swelling law is obeyed in the microemulsion system.
PMID- 26439625
TI - Whole Blood Gene Expression Profiles of Patients with a Past Aneurysmal
Subarachnoid Hemorrhage.
AB - BACKGROUND: The pathogenesis of development and rupture of intracranial aneurysms
(IA) is largely unknown. Also, screening for IA to prevent aneurysmal
subarachnoid hemorrhage (aSAH) is inefficient, as disease markers are lacking. We
investigated gene expression profiles in blood of previous aSAH patients, who are
still at risk for future IA, aiming to gain insight into the pathogenesis of IA
and aSAH, and to make a first step towards improvement of aSAH risk prediction.
METHODS AND RESULTS: We collected peripheral blood of 119 patients with aSAH at
least two years prior, and 118 controls. We determined gene expression profiles
using Illumina HumanHT-12v4 BeadChips. After quality control, we divided the
dataset in a discovery (2/3) and replication set (1/3), identified differentially
expressed genes, and applied (co-)differential co-expression to identify disease
related gene networks. No genes with a significant (false-discovery rate <5%)
differential expression were observed. We detected one gene network with
significant differential co-expression, but did not find biologically meaningful
gene networks related to a history of aSAH. Next, we applied prediction analysis
of microarrays to find a gene set that optimally predicts absence or presence of
a history of aSAH. We found no gene sets with a correct disease state prediction
higher than 40%. CONCLUSIONS: No gene expression differences were present in
blood of previous aSAH patients compared to controls, besides one differentially
co-expressed gene network without a clear relevant biological function. Our
findings suggest that gene expression profiles, as detected in blood of previous
aSAH patients, do not reveal the pathogenesis of IA and aSAH, and cannot be used
for aSAH risk prediction.
PMID- 26439626
TI - Size effects in the magnetic anisotropy of embedded cobalt nanoparticles: from
shape to surface.
AB - Strong size-dependent variations of the magnetic anisotropy of embedded cobalt
clusters are evidenced quantitatively by combining magnetic experiments and
advanced data treatment. The obtained values are discussed in the frame of two
theoretical models that demonstrate the decisive role of the shape in larger
nanoparticles and the predominant role of the surface anisotropy in clusters
below 3 nm diameter.
PMID- 26439627
TI - Comparison of the Five Danish Regions Regarding Demographic Characteristics,
Healthcare Utilization, and Medication Use--A Descriptive Cross-Sectional Study.
AB - BACKGROUND: While Denmark is well known for its plethora of registers. Many
studies are conducted on research databases that only cover parts of Denmark, and
regional differences could potentially threaten these studies' external validity.
The aim of this study was to assess sociodemographic and health related
homogeneity of the five Danish regions. METHODS: We obtained descriptive data for
the five Danish regions, using publicly available data sources: Statbank Denmark,
the Danish Ministry of Economic Affairs, and Medstat.dk. These data sources
comprise aggregate data from four different nationwide registers: The Danish
National Patient Register, The Danish Civil Registration System, The Danish
Register of Medicinal Product Statistics, and The Danish National Health Service
Register for Primary Care. We compared the Danish regions regarding demographic
and socioeconomic characteristics, health care utilization, and use of
medication. For each characteristic, one-year prevalence was obtained and
analyses were performed for 2013 and 2008 to account for possible change over
time. RESULTS: In 2013, 5,602,628 persons were living in Denmark. The mean age
was 40.7 years in the entire Danish population and ranged between 39.6 to 42.4
years in the five regions (coefficient of variation between regions [CV] =
0.028). The proportion of women in Denmark was 50.4% (CV = 0.009). The proportion
of residents with low education level was 28.7% (CV = 0.051). The annual number
of GP contacts was 7.1 (range: 6.7-7.4, CV = 0.040), and 114 per 1,000 residents
were admitted to the hospital (range: 101-131, CV = 0.107). The annual number of
persons redeeming a prescription of any medication was 723 per 1,000 residents
(range: 718-743, CV = 0.016). Analyses for 2008 showed comparable levels of
homogeneity as for 2013. CONCLUSIONS: We found substantial homogeneity between
all of the five Danish regions with regard to sociodemographic and health related
characteristics. Epidemiologic studies conducted on regional subsets of Danish
citizens have a high degree of generalizability.
PMID- 26439628
TI - Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and
Localized Disease Pattern in the Early Stage.
AB - BACKGROUND: Non-eosinophilic nasal polyps (NPs) show less inflammatory changes
and are less commonly associated with lower airway inflammatory disorders such as
asthma, compared with eosinophilic NPs. However, the development of non
eosinophilic NPs which is a predominant subtype in Asian population still remains
unclear. METHODS: A total of 81 patients (45 with non-eosinophilic NPs and 36
with eosinophilic NPs) were enrolled. Clinical information and computed
tomography (CT), endoscopic, and histological findings were investigated. Tissue
samples were analyzed for total IgE levels and for mRNA expression levels of
interleukin (IL)-4, IL-5, IL-13, interferon (IFN)-gamma, tumor necrosis factor
(TNF)-alpha, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF)-beta1, TGF
beta2, TGF-beta3, and periostin. Immunostaining assessment of Ki-67 as a
proliferation marker was performed. RESULTS: We found that epithelial in-growing
patterns such as pseudocysts were more frequently observed in histological and
endoscopic evaluations of non-eosinophilic NPs, which was linked to increase
epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were
characterized by high infiltration of inflammatory cells, compared with non
eosinophilic NPs. To investigate the developmental course of each subtype, CT was
analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more
localized pattern and maxillary sinus involvement, but lesser olfactory
involvement in early stage whereas eosinophilic NPs were characterized by diffuse
ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M)
CT scores, indicating ethmoidal dominant involvement, were one of surrogate
markers for eosinophilic NP. E/M CT scores was positively correlated with levels
of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and
total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- gamma were
inversely correlated. Moreover, if the combinatorial algorithm meet the three of
the four markers, including IL-5 (<2.379), periostin (<3.889), IFN-gamma
(>0.316), and E/M ratio (<2.167), non-eosinophilic CRSwNP are diagnosed with a
sensitivity of 84.4% and a specificity of 84.8%. CONCLUSION: Histologic,
immunologic and clinical data suggest that non-eosinophilic NPs showed enhanced
epithelial alteration and more localized maxillary involvement. Combination of
cutoff value on IL-5, periostin, IFN-gamma, and E/M scores may be one of
surrogate markers for non-eosinophil NP subtype.
PMID- 26439629
TI - Unusual spin dynamics in topological insulators.
AB - The dynamic spin susceptibility (DSS) has a ubiquitous Lorentzian form around the
Zeeman energy in conventional materials with weak spin orbit coupling, whose
spectral width characterizes the spin relaxation rate. We show that DSS has an
unusual non-Lorentzian form in topological insulators, which are characterized by
strong SOC, and the anisotropy of the DSS reveals the orientation of the
underlying spin texture of topological states. At zero temperature, the high
frequency part of DSS is universal and increases in certain directions as omega(d
1) with d = 2 and 3 for surface states and Weyl semimetals, respectively, while
for helical edge states, the interactions renormalize the exponent as d = 2K - 1
with K the Luttinger-liquid parameter. As a result, spin relaxation rate cannot
be deduced from the DSS in contrast to the case of usual metals, which follows
from the strongly entangled spin and charge degrees of freedom in these systems.
PMID- 26439631
TI - Decomposition characteristics of humic-like matters with the hollow ellipsoid
structure sludge inoculated from decayed soil in mature landfill leachate.
AB - The organics in mature leachate are mainly humic-like matters, which account for
over 80% weight of the total organics. In this work, the microorganisms in
decayed soil were found to be capable of decomposing the humic-like matters
evidently using an anaerobic-aerobic/anoxic bioprocess in two sequencing bio
reactors. The 3D excitation-emission matrix and Fourier transform infrared (FT
IR) were applied to characterize the variation of dissolved organic matters in
mature leachate while sludge morphology was characterized by scanning electron
microscopy. The intensities of fluorescence peaks A and C of leachate effluents
were 71.66% and 48.75% lower than those of influents, respectively, which
indicated the extraordinary degradation ability of microorganisms inoculated from
the decayed soil. Meanwhile a kind of distinctive hollow ellipsoid structure
sludge organized by tiny soil particles was observed, which might favour the
humic-like matters' decomposition and has never been reported before as we know.
The formation mechanisms of hollow ellipsoid structure sludge will need further
study.
PMID- 26439630
TI - Lactobacillus rhamnosus CNCMI-4317 Modulates Fiaf/Angptl4 in Intestinal
Epithelial Cells and Circulating Level in Mice.
AB - BACKGROUND AND OBJECTIVES: Identification of new targets for metabolic diseases
treatment or prevention is required. In this context, FIAF/ANGPTL4 appears as a
crucial regulator of energy homeostasis. Lactobacilli are often considered to
display beneficial effect for their hosts, acting on different regulatory
pathways. The aim of the present work was to study the effect of several
lactobacilli strains on Fiaf gene expression in human intestinal epithelial cells
(IECs) and on mice tissues to decipher the underlying mechanisms. SUBJECTS AND
METHODS: Nineteen lactobacilli strains have been tested on HT-29 human intestinal
epithelial cells for their ability to regulate Fiaf gene expression by RT-qPCR.
In order to determine regulated pathways, we analysed the whole genome
transcriptome of IECs. We then validated in vivo bacterial effects using C57BL/6
mono-colonized mice fed with normal chow. RESULTS: We identified one strain
(Lactobacillus rhamnosus CNCMI-4317) that modulated Fiaf expression in IECs. This
regulation relied potentially on bacterial surface-exposed molecules and seemed
to be PPAR-gamma independent but PPAR-alpha dependent. Transcriptome functional
analysis revealed that multiple pathways including cellular function and
maintenance, lymphoid tissue structure and development, as well as lipid
metabolism were regulated by this strain. The regulation of immune system and
lipid and carbohydrate metabolism was also confirmed by overrepresentation of
Gene Ontology terms analysis. In vivo, circulating FIAF protein was increased by
the strain but this phenomenon was not correlated with modulation Fiaf expression
in tissues (except a trend in distal small intestine). CONCLUSION: We showed that
Lactobacillus rhamnosus CNCMI-4317 induced Fiaf expression in human IECs, and
increased circulating FIAF protein level in mice. Moreover, this effect was
accompanied by transcriptome modulation of several pathways including immune
response and metabolism in vitro.
PMID- 26439633
TI - Erythematous Variety of Bullous Pemphigoid: Case Report and Literature Review.
PMID- 26439632
TI - Endovascular Management of Post-Irradiated Carotid Blowout Syndrome.
AB - PURPOSE: To retrospectively evaluate the clinical and technical factors related
to the outcomes of endovascular management in patients with head-and-neck cancers
associated with post-irradiated carotid blowout syndrome (PCBS). MATERIALS AND
METHODS: Between 2000 and 2013, 96 patients with PCBS underwent endovascular
management. The 40 patients with the pathological lesions located in the external
carotid artery were classified as group 1 and were treated with embolization. The
other 56 patients with the pathological lesions located in the trunk of the
carotid artery were divided into 2 groups as follows: group 2A comprised the 38
patients treated with embolization, and group 2B comprised the 18 patients
treated with stent-graft placement. Fisher's exact test was used to examine
endovascular methods, clinical severities, and postprocedural clinical diseases
as predictors of outcomes. RESULTS: Technical success and immediate hemostasis
were achieved in all patients. The results according to endovascular methods
(group 1 vs 2A vs 2B) were as follows: technical complication (1/40[2.5%] vs
9/38[23.7%] vs 9/18[50.0%], P = 0.0001); rebleeding (14/40[35.0%] vs 5/38[13.2%]
vs 7/18[38.9%]), P = 0.0435). The results according to clinical severity (acute
vs ongoing PCBS) were as follows: technical complication (15/47[31.9%] vs
4/49[8.2%], P = 0.0035); rebleeding (18/47[38.3%] vs 8/49[16.3%], P = 0.0155).
The results according to post-procedural clinical disease (regressive vs
progressive change) were as follows: alive (14/21[66.7%] vs 8/75[10.7%],
P<0.0001); survival time (34.1+/-30.6[0.3-110] vs 3.6+/-4.0[0.07-22] months,
P<0.0001). CONCLUSION: The outcomes of endovascular management of PCBS can be
improved by taking embolization as a prior way of treatment, performing
endovascular intervention in slight clinical severity and aggressive management
of the post-procedural clinical disease.
PMID- 26439634
TI - Source-ful science.
PMID- 26439635
TI - Solute carriers keep on rockin'.
PMID- 26439636
TI - Molecular prejudice: RNA discrimination against purines allows response to a
cellular alarm.
PMID- 26439637
TI - SEC-uring membrane fusion: a sneak peek at SNARE-complex assembly driven by Sec1
Munc18 proteins.
PMID- 26439638
TI - Reversible aggregation after heat shock.
PMID- 26439640
TI - DNA nano-carrier for repeatable capture and release of biomolecules.
AB - DNA can be manipulated to design nano-machines through specific sequence
recognition. We report a switchable DNA carrier for repeatable capture and
release of a single stranded DNA. The activity of the carrier was regulated by
the interactions among a double-stranded actuator, single stranded target, fuel,
and anti-fuel DNA strands. Inosine was used to maintain a stable triple-stranded
complex when the actuator's conformation was switched between open (capture) and
closed (release) configurations. Time lapse fluorescence measurements show
repeatable capture and release of target strands. TEM images also show visible
capture of target DNA strands when gold nanoparticles were attached to the DNA
carrier and the target DNA strand. The carrier activity was controlled by length
of toeholds, number of mismatches, and inosine substitutions. Significantly,
unlike in previously published work that reported the devices functioned only
when there is a perfect match between the interacting DNA strands, the present
device works only when there are mismatches in the fuel strand and the best
performance is achieved for 1-3 mismatches. The device was used to successfully
capture and release gold nanoparticles when linked to the target single-stranded
DNA. In general, this type of devices can be used for transport and delivery of
theranostic molecules.
PMID- 26439639
TI - Neuronal activity regulates remyelination via glutamate signalling to
oligodendrocyte progenitors.
AB - Myelin regeneration can occur spontaneously in demyelinating diseases such as
multiple sclerosis (MS). However, the underlying mechanisms and causes of its
frequent failure remain incompletely understood. Here we show, using an in-vivo
remyelination model, that demyelinated axons are electrically active and generate
de novo synapses with recruited oligodendrocyte progenitor cells (OPCs), which,
early after lesion induction, sense neuronal activity by expressing AMPA (alpha
amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptors. Blocking
neuronal activity, axonal vesicular release or AMPA receptors in demyelinated
lesions results in reduced remyelination. In the absence of neuronal activity
there is a ~6-fold increase in OPC number within the lesions and a reduced
proportion of differentiated oligodendrocytes. These findings reveal that
neuronal activity and release of glutamate instruct OPCs to differentiate into
new myelinating oligodendrocytes that recover lost function. Co-localization of
OPCs with the presynaptic protein VGluT2 in MS lesions implies that this
mechanism may provide novel targets to therapeutically enhance remyelination.
PMID- 26439641
TI - Pharmacogenetic Effect of Complement Factor H Gene Polymorphism in Response to
the Initial Intravitreal Injection of Bevacizumab for Wet Age-Related Macular
Degeneration.
AB - PURPOSE: To compare the functional and morphological response to the initial
intravitreal (IVT) injection of bevacizumab in exudative age-related macular
degeneration (AMD) patients with the complement factor H (CFH) gene polymorphism
T1277C in the Brazilian population. METHODS: Twenty-five unrelated patients with
treatment-naive exudative AMD underwent an IVT injection of 1.25 mg bevacizumab
at the initial presentation (D0) and were reexamined 7 days (D7) and 28 days
(D28) later. The time and extent of visual acuity (VA) and central retinal
thickness (CRT) changes were evaluated according to the presence of the T1277C
polymorphism. RESULTS: In the homozygous risk group (CC), VA improvement was
detected mostly from D7 to D28, while in the heterozygous (CT) and homozygous for
the wild-type allele (TT) groups, functional response occurred earlier, from D0
to D7. Morphological response to the first IVT injection of bevacizumab was
significant in the CT and TT groups, while the CC group presented no significant
change in CRT up to D28. CONCLUSION: The CC variant of the CFH gene polymorphism
T1277C is related to delayed functional and limited morphological response to the
initial IVT injection of bevacizumab in exudative AMD patients in a sample of the
Brazilian population.
PMID- 26439642
TI - Bile sequestration potential of an edible mineral (clinoptilolite) under
simulated digestion of a high-fat meal: an in vitro investigation.
AB - Bile, important for cholesterol homeostasis, is a potential target of
hypercholesterolemia management. Bile sequestration by orally administered
resins, while mostly effective in reducing blood cholesterol, presents several
side effects and disadvantages. Thus, widely available natural edible minerals
such as clinoptilolite with adsorptive properties offer an alternative for bile
sequestration. In an experimental setting mimicking the physiological conditions
of digestion/absorption (pH, temperature, and retention times) with a series of
assessment methods, scanning electron microscopy-energy dispersion X-ray analysis
(SEM-EDX), X-ray diffraction (XRD), Fourier transform infrared analysis (FT-IR),
thermogravimetric differential thermal analysis (TG-DTA), and molecular docking
modeling, the ability of natural unmodified clinoptilolite to retain bile, while
mixed with a simulated high-fat meal, was investigated. Our results demonstrate
that clinoptilolite sequesters bile via adsorption of macromicelles at 75.4%
efficiency, when the former is administered at a reasonable dose of 4% (w/w) of a
meal's weight. This work provides the possibility of clinoptilolite utilization
as a bile-sequestering/cholesterol-reducing agent.
PMID- 26439643
TI - Measurement of molecular mixing at a conjugated polymer interface by specular and
off-specular neutron scattering.
AB - Measurements have been performed on thermally equilibrated conjugated
polymer/insulating-polymer bilayers, using specular and off-specular neutron
reflectivity. While specular reflectivity is only sensitive to the structure
normal to the sample, off-specular measurements can probe the structure of the
buried polymer/polymer interface in the plane of the sample. Systematic analysis
of the scattering from a set of samples with varying insulating-polymer
thickness, using the distorted-wave Born approximation (DWBA), has allowed a
robust determination of the intrinsic width at the buried polymer/polymer
interface. The quantification of this width (12 A +/- 4 A) allows us to examine
aspects of the conjugated polymer conformation at the interface, by appealing to
self-consistent field theory (SCFT) predictions for equilibrium polymer/polymer
interfaces in the cases of flexible and semi-flexible chains. This analysis
enables us to infer that mixing at this particular interface cannot be described
in terms of polymer chain segments that adopt conformations similar to a random
walk. Instead, a more plausible explanation is that the conjugated polymer chain
segments become significantly oriented in the plane of the interface. It is
important to point out that we are only able to reach this conclusion following
the extensive analysis of reflectivity data, followed by comparison with SCFT
predictions. It is not simply the case that conjugated polymers would be expected
to adopt this kind of oriented conformation at the interface, because of their
relatively high chain stiffness. It is the combination of a high stiffness and a
relatively narrow intrinsic interfacial width that results in a deviation from
flexible chain behaviour.
PMID- 26439644
TI - Improvement of the butanol production selectivity and butanol to acetone ratio
(B:A) by addition of electron carriers in the batch culture of a new local
isolate of Clostridium acetobutylicum YM1.
AB - Improvement in the butanol production selectivity or enhanced butanol:acetone
ratio (B:A) is desirable in acetone-butanol-ethanol (ABE) fermentation by
Clostridium strains. In this study, artificial electron carriers were added to
the fermentation medium of a new isolate of Clostridium acetobutylicum YM1 in
order to improve the butanol yield and B:A ratio. The results revealed that
medium supplementation with electron carriers changed the metabolism flux of
electron and carbon in ABE fermentation by YM1. A decrease in acetone production,
which subsequently improved the B:A ratio, was observed. Further improvement in
the butanol production and B:A ratios were obtained when the fermentation medium
was supplemented with butyric acid. The maximum butanol production (18.20 +/-
1.38 g/L) was gained when a combination of methyl red and butyric acid was added.
Although the addition of benzyl viologen (0.1 mM) and butyric acid resulted in
high a B:A ratio of 16:1 (800% increment compared with the conventional 2:1
ratio), the addition of benzyl viologen to the culture after 4 h resulted in the
production of 18.05 g/L butanol. Manipulating the metabolic flux to butanol
through the addition of electron carriers could become an alternative strategy to
achieve higher butanol productivity and improve the B:A ratio.
PMID- 26439645
TI - Effect of application rate on fumigant degradation in five agricultural soils.
AB - Soil fumigation is an important pest management tool for many high value crops.
To address the knowledge gap of how fumigant concentration in soil impacts
dissipation, and thereby efficacy, this research determined the degradation
characteristics of four fumigants as affected by application rate. Laboratory
incubation experiments were conducted to determine degradation rates of 1,3
dichloropropene (both cis- and trans isomers), chloropicrin (CP), dimethyl
disulfide (DMDS), and methyl iodide (MeI) in five agricultural soils. Fitted to
pseudo first-order kinetics, the degradation rate constant (k) of CP, DMDS, and
MeI decreased significantly as application rate increased while the 1,3-D isomers
were the least affected by rate. Half-lives increased 12, 17, and 6-fold for CP,
DMDS, and MeI, respectively, from the lowest to the highest application rate. At
low application rates, the degradation rate of all fumigants in the Hueneme sandy
loam soil was reduced by 50-95% in sterilized soil compared to the biologically
active controls. However, this difference became much smaller or disappeared at
high application rates indicating that biodegradation dominates at low
concentrations but chemical degradation is more important at high concentrations.
When co-applied, CP degradation was enhanced with biodegradation remained above
50%, while 1,3-D degradation was either reduced or not changed. Among the
fumigants tested, the relative importance of biodegradation was DMDS>CP>MeI>1,3
D. These results are useful for determining effective fumigation rates and for
informing regulatory decisions on emission controls under different fumigation
scenarios.
PMID- 26439646
TI - Commuter exposure to inhalable, thoracic and alveolic particles in various
transportation modes in Delhi.
AB - A public health concern is to understand the linkages between specific pollution
sources and adverse health impacts. Commuting can be viewed as one of the
significant-exposure activity in high-vehicle density areas. This paper
investigates the commuter exposure to inhalable, thoracic and alveolic particles
in various transportation modes in Delhi, India. Air pollution levels are
significantly contributed by automobile exhaust and also in-vehicle exposure can
be higher sometime than ambient levels. Motorcycle, auto rickshaw, car and bus
were selected to study particles concentration along two routes in Delhi between
Kashmere Gate and Dwarka. The bus and auto rickshaw were running on compressed
natural gas (CNG) while the car and motorcycle were operated on gasoline fuel.
Aerosol spectrometer was employed to measure inhalable, thoracic and alveolic
particles during morning and evening rush hours for five weekdays. From the
study, we observed that the concentration levels of these particles were greatly
influenced by transportation modes. Concentrations of inhalable particles were
found higher during morning in auto rickshaw (332.81 +/- 90.97 MUg/m(3)) while
the commuter of bus exhibited higher exposure of thoracic particles (292.23 +/-
110.45 MUg/m(3)) and car commuters were exposed to maximum concentrations of
alveolic particles (222.37 +/- 26.56 MUg/m(3)). We observed that in evening car
commuters experienced maximum concentrations of all sizes of particles among the
four commuting modes. Interestingly, motorcycle commuters were exposed to lower
levels of inhalable and thoracic particles during morning and evening hours as
compared to other modes of transport. The mean values were found greater than the
median values for all the modes of transport suggesting that positive skewed
distributions are characteristics of naturally occurring phenomenon.
PMID- 26439647
TI - Environmental fate of the insecticide cypermethrin applied as microgranular and
emulsifiable concentrate formulations in sunflower cultivated field plots.
AB - A field dissipation and transport study of the insecticide cypermethrin applied
as microgranular (MG) and emulsifiable concentrate (EC) formulations has been
conducted in field sunflower cultivations and bare soil plots with two different
slopes (1% and 5%). The dissipation of insecticide in soil (on planting rows) was
monitored for a period of 193 days. Cypermethrin residual concentrations in the
upper soil layer (0-10 cm), 2 days after soil application (DASA), ranged from
0.53 to 0.73 MUg g(- 1) when the maximum values were observed 7 DASA, ranged from
1.06 to 1.23 MUg g(-1). The dissipation rate was better described by first-order
kinetics. The average half-life in cultivated (tilled and planted) plots was
23.07 and 24.24 days for soil slopes 5% and 1%, respectively. In uncultivated
(tilled but not planted) plots the respective values were 22.01 and 22.37 days.
The insecticide was found below the 10 cm soil layer occasionally in few samples
at low concentrations (< 0.02 MUg g(- 1)). In runoff water it was detected once
(7 days after foliar application, at levels below LOQ), when in sediment it was
detectable for seven samplings. The maximum values were observed 7 days after
foliar application, when they reached 0.097 and 0.143 MUg g(-1) in cultivated
plots with soil slopes 1% and 5%; and 0.394 and 0.500 MUg g(-1) in uncultivated
plots, respectively. The amount of cypermethrin which was transferred by the
sediment remained at low levels (less than 0.01% of the totally applied active
ingredient), even in plots with 5% inclination. The insecticide was detected in
leaves and stems of the sunflower plants after the foliar application up to the
day of harvest. On the contrary, in roots it was detectable during the whole
cultivation period. No residues were detected in flowers or seeds.
PMID- 26439648
TI - Temporal-spatial loss of diffuse pesticide and potential risks for water quality
in China.
AB - Increasing amount of pesticide has been used in Chinese agricultural system with
effects on environmental quality and human health. The comprehensive inventory of
pesticide use in six main crop categories over the period from 1990 to 2011 in
China was conducted. The national average pesticide use intensity was estimated
1.74k g . ha(-1) for grain crops in paddy land, 1.31 kg . ha(-1) for grain crops
in dry land, 1.38 kg . ha(-1) for economic crops, 3.82 kg . ha(-1) for
vegetables, 1.54 kg . ha(-1) for tea plantations, and 3.49 kg . ha(-1) for
orchards. The pesticide use was estimated to be approximately 5.24 * 10(4)t for
grain crops in paddy land, 1.05 * 10(5)t for grain crops in dry land, 3.08 *
10(4)t for economic crops, 7.51 * 10(4)t for vegetables, 3.26 * 10(3)t for tea
plantations, and 4.13 * 10(4)t for orchards. Based on the pesticide use and loss
coefficients for each category, the distribution of pesticide loss in China was
calculated. Total pesticide loss in China was estimated about 4.39 * 10(3)t in
2011. The pesticide loss from six main crop categories was about 14.84% for grain
crops in paddy land of total pesticide loss, 33.31% for grain crops in dry land,
10.47% for economic crops, 26.37% for vegetables, 1.08% for tea plantations and
13.93% for orchards. The results indicated that the highest pesticide use
intensity and highest pesticide loss rate occurred in China's eastern and central
provinces. The Monte Carlo simulation was used to quantify the uncertainties
associated with estimation of pesticide use and loss rate for the six types of
crops. The potential risk to national water quality was assessed and the water in
the provinces of Henan, Shandong, Hebei, Beijing and Shanghai was at high risk
for pesticide pollution. The implication for the future agricultural and
environmental policies on reducing the risk to environmental quality was also
summarized.
PMID- 26439649
TI - A methodological framework to assess the socio-economic impact of underground
quarries: A case study from Belgian Limburg.
AB - This study developed a methodology to assess the socio-economic impact of the
presence and collapse of underground limestone quarries. For this we rely on case
study evidence from Riemst, a village located in Eastern Belgium and use both
secondary and primary data sources. A sinkhole inventory as well as data about
the prevention costs provided by the municipality was used. To estimate the
recreational values of the quarries, visitor data was obtained from the tourist
office of Riemst. Next, two surveys were conducted among inhabitants and four
real estate agents and one notary. The direct and indirect damages were assessed
using respectively the repair cost and production and real estate value losses.
The total yearly direct and indirect damage equals ?415000 (+/-?85000) and more
than half of it can be attributed to the depreciation of real estate (?230000).
The quarries have recreational, cultural-historical and ecological values and
thus generate societal benefits. The yearly recreational value was at least
?613000 in 2012 values. The ecological and cultural-historical values augment to
?180000 per year (in 2012 values). Further, our study indicates that the gains
from filling up the quarries below the houses located above an underground
limestone quarry outweigh the costs in the case study area. The net gain from
filling up the underground quarry ranges ?38700 to ?101700 per house. This is
only the lower bound of the net gain from filling up these underground quarries
since preventive filling makes future collapses less likely so that future direct
repair costs will be most likely smaller.
PMID- 26439650
TI - Stability of nTiO2 particles and their attachment to sand: Effects of humic acid
at different pH.
AB - The fate and transport of nano-scale or micro-scale titanium dioxide particles
(nTiO2) in subsurface environments are strongly influenced by the stability of
nTiO2 and their attachment to sediment grains. nTiO2 may carry either positive or
negative charges in natural water, therefore, environmental factors such as pH,
humic substances, and Fe oxyhydroxide coatings on sediment grains, which are
known to control the stability and transport of negatively-charged colloids, may
influence nTiO2 in different manners. The objective of this study is to
investigate the effects of pH and humic acid (HA) on the stability and attachment
of nTiO2 to sand at HA concentrations that are relevant to typical groundwater
conditions, so that mechanisms that control nTiO2 immobilization and transport in
natural systems can be elucidated. Stability and attachment of nTiO2 to quartz
sand and Fe oxyhydroxide coated quartz sand are experimentally measured under a
range of HA concentrations at pH5 and 9. Results show that at pH5, negatively
charged HA strongly adsorbs to positively-charged nTiO2 and Fe oxyhydroxide,
which, at low HA concentrations, partially neutralizes the positive charges on
nTiO2 and Fe oxyhydroxide, and therefore decreases the repulsive electrostatic
forces between the surfaces, resulting in nTiO2 aggregation and attachment. At
high HA concentrations, adsorbed HA reverses the surface charges of nTiO2 and Fe
oxyhydroxide, and makes nTiO2 and Fe oxyhydroxide strongly negatively charged,
resulting in stable nTiO2 suspension and low nTiO2 attachment. At pH9, HA, nTiO2,
and Fe oxyhydroxide are all negatively charged, and HA adsorption is low and does
not have a strong impact on the stability and attachment of nTiO2. Overall, this
study shows that changes in surface charges of nTiO2 and Fe oxyhydroxide coating
caused by HA adsorption is a key factor that influences the stability and
attachment of nTiO2.
PMID- 26439651
TI - Lipophilicity of PCBs and fatty acids determines their mobilisation from blubber
of weaned northern elephant seal pups.
AB - Polychlorinated biphenyls (PCBs) exhibit lipophilic properties that lead to their
bioaccumulation in adipose tissue. Following PCB exposition, northern elephant
seals (Mirounga angustirostris) concentrate high amounts of these pollutants in
their large adipose tissue stores. During lipolytic periods such as the post
weaning fast, fatty acids (FAs), which form triglycerides, and PCBs are both
mobilised from adipose tissue. Our results showed that the degree of
lipophilicity of FAs and PCBs impacted their release: the more lipophilic FAs and
PCBs tended to be more conserved in blubber over the fast than the less
lipophilic ones. This led to an enrichment of more lipophilic compounds within
adipocytes with the progression of the fast. Life history patterns that include
fasting may thus influence the profile of blubber lipids and contaminants.
PMID- 26439652
TI - Estimation of alcohol consumption during "Fallas" festivity in the wastewater of
Valencia city (Spain) using ethyl sulfate as a biomarker.
AB - Alcohol consumption has been increasing in the last years and it has become a
sociological problem due its derived health and safety problems. Ethyl sulfate is
a secondary metabolite of the alcohol degradation that is excreted through the
urine (0.010-0.016%) after alcohol ingestion and it is quite stable in water. In
this study, a new methodology to determine ethyl sulfate by ion-pair liquid
chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Different ion
pairs and additives were tested directly in the sample extracts or in the mobile
phase. The best ion-pair was set up adding 0.5M of tributylamine and 0.1% of
formic acid to the sample. The limit of quantification was 0.3 MUg L(-1) and the
intra-day and inter-day precision of the method were <= 2.8 and <= 3.0%,
respectively. Good linearity (r(2)<0.999) and low matrix effect (<30% corrected
by using internal isotopically labelled internal standard) were achieved. The
sampling campaign was from 4th to 20th March of 2014 covering the festivity of
Fallas (15th to 19th March). Ethyl sulfate was determined in all influents of the
3 wastewater treatment plants (Pinedo I, Pinedo II and Quart-Benager) belonging
to Valencia and surrounding area. Ethyl sulfate concentrations ranged from 1.46
to 19.85 MUg L(-1) and alcohol consumption ranged from 1.07 to 56.11 mL day(-1)
inhab(-1), being the highest value of alcohol consumption determined during
Fallas. This study presents a reliable and alternative method to traditional ones
to determine alcohol consumption by population that provides real-time
information of alcohol consumption.
PMID- 26439653
TI - Effects of legume species introduction on vegetation and soil nutrient
development on abandoned croplands in a semi-arid environment on the Loess
Plateau, China.
AB - Revegetation facilitated by legume species introduction has been used for soil
erosion control on the Loess Plateau, China. However, it is still unclear how
vegetation and soil resources develop during this restoration process, especially
over the longer term. In this study, we investigated the changes of plant
aboveground biomass, vegetation cover, species richness and density of all
individuals, and soil total nitrogen, mineral nitrogen, total phosphorus and
available phosphorus over 11 years from 2003 to 2013 in three treatments (natural
revegetation, Medicago sativa L. introduction and Melilotus suaveolens L.
introduction) on the semi-arid Loess Plateau. Medicago significantly increased
aboveground biomass and vegetation cover, and soil total nitrogen and mineral
nitrogen contents. The Medicago treatment had lower species richness and density
of all individuals, lower soil moisture in the deep soil (i.e., 1.4-5m), and
lower soil available phosphorus. Melilotus introduction significantly increased
aboveground biomass in only the first two years, and it was not an effective
approach to improve vegetation biomass and cover, and soil nutrients, especially
in later stages of revegetation. Overall, our study suggests that M. sativa can
be the preferred plant species for revegetation of degraded ecosystems on the
Loess Plateau, although phosphorus fertilizer should be applied for the
sustainability of the revegetation.
PMID- 26439654
TI - European Code against Cancer 4th Edition: Process of reviewing the scientific
evidence and revising the recommendations.
AB - The European Code Against Cancer is a set of recommendations to give advice on
cancer prevention. Its 4th edition is an update of the 3rd edition, from 2003.
Working Groups of independent experts from different fields of cancer prevention
were appointed to review the recommendations, supported by a Literature Group to
provide scientific and technical support in the assessment of the scientific
evidence, through systematic reviews of the literature. Common procedures were
developed to guide the experts in identifying, retrieving, assessing,
interpreting and summarizing the scientific evidence in order to revise the
recommendations. The Code strictly followed the concept of providing advice to
European Union citizens based on the current best available science. The advice,
if followed, would be expected to reduce cancer risk, referring both to avoiding
or reducing exposure to carcinogenic agents or changing behaviour related to
cancer risk and to participating in medical interventions able to avert specific
cancers or their consequences. The information sources and procedures for the
review of the scientific evidence are described here in detail. The 12
recommendations of the 4th edition of the European Code Against Cancer were
ultimately approved by a Scientific Committee of leading European cancer and
public health experts.
PMID- 26439655
TI - Benzodiazepines induce sequelae in immature mice with inflammation-induced status
epilepticus.
AB - OBJECTIVE: Since benzodiazepines (BZPs) became clinically available for the
treatment of status epilepticus (SE) in children, the incidence of neurological
sequelae has increased. However, the cause-effect relationship is poorly
understood. In this paper, we examined the effect of BZPs on an inflammation
induced SE (iSE) animal model. METHOD: Inflammation was induced by injecting
poly(I:C) (pIC 10 mg/kg, postnatal day 12-14), seizure was induced by injecting
pilocarpine hydrochloride (PILO 200 mg/kg, postnatal day 15) into C57BL/6J mice,
and the pIC+PILO mice were used as the iSE model (miSE). The GABA-A receptor
agonist midazolam (MDL 0.5 mg/kg) was used to inhibit seizures. Sequelae were
evaluated by performing behavior and immunohistochemical analyses in the chronic
phase. RESULT: The exploratory activity of mice in the miSE plus MDL group
increased significantly, indicating that hyperactivity was newly induced by MDL
in miSE mice. The contextual fear memory of the miSE mice was also significantly
increased and that of miSE treated with MDL returned to the normal level. The
parvalbumin-positive GABA neurons were decreased in number by pIC+PILO which was
rescued by MDL. Apoptosis marker ssDNA-positive cells were increased by pIC+PILO
which could not be rescued by MDL. Therefore, we propose that BZP-dependent
therapy for SE needs to be rethought from the perspective of using other
treatment approaches.
PMID- 26439656
TI - Seizure detection approach using S-transform and singular value decomposition.
AB - Automatic seizure detection plays a significant role in the diagnosis of
epilepsy. This paper presents a novel method based on S-transform and singular
value decomposition (SVD) for seizure detection. Primarily, S-transform is
performed on EEG signals, and the obtained time-frequency matrix is divided into
submatrices. Then, the singular values of each submatrix are extracted using
singular value decomposition (SVD). Effective features are constructed by adding
the largest singular values in the same frequency band together and fed into
Bayesian linear discriminant analysis (BLDA) classifier for decision. Finally,
postprocessing is applied to obtain higher sensitivity and lower false detection
rate. A total of 183.07 hours of intracranial EEG recordings containing 82
seizure events from 20 patients were used to evaluate the system. The proposed
method had a sensitivity of 96.40% and a specificity of 99.01%, with a false
detection rate of 0.16/h.
PMID- 26439657
TI - Evaluate the efficacy of minimum attenuation value in differentiation of adrenal
adenomas from nonadenomas on unenhanced CT.
AB - Most adrenal masses are adenomas which contain a large amount of intracytoplasmic
lipid and have lower attenuation values on unenhanced computed tomography (CT)
examinations. Mean atrioventricular and CT histogram analysis is commonly used
for the diagnosis of adenomas; however, the former disregards tissue
heterogeneities of the mass and diagnostic efficiency is decreased, and the
latter demands specific post-processing workstation for analyzing the data. The
purpose of our study is to develop a simple and sensitive method for the
diagnosis of adenomas on unenhanced CT.
PMID- 26439659
TI - Priming of pathogenesis related-proteins and enzymes related to oxidative stress
by plant growth promoting rhizobacteria on rice plants upon abiotic and biotic
stress challenge.
AB - Two plant growth promoting rhizobacteria (PGPR) were tested to evaluate their
capacity to prime rice seedlings against stress challenge (salt and Xanthomonas
campestris infection). As is accepted that plants respond to biotic and abiotic
stresses by generation of reactive oxygen species (ROS), enzyme activities
related to oxidative stress (ascorbate peroxidase (APX, EC 1.11.1.11), guaiacol
peroxidase (GPX, EC 1.11.1.7), glutathione reductase (GR, EC 1.6.4.2) and
superoxide dismutase (SOD, EC 1.15.1.1)) as well as the pathogenesis-related
proteins (PRs) beta-1,3-glucanase (PR2, EC 3.2.1.6) and chitinase (PR3, EC
3.2.1.14) were measured at 3 time points after stress challenge. In addition,
photosynthetic parameters related with fluorescence emission of photosystem II
(F0, Fv/Fm, PhiPSII and NPQ) were also measured although they were barely
affected. Both strains were able to protect rice seedlings against salt stress.
AMG272 reduced the salt symptoms over 47% with regard to control, and L81 over
90%. Upon pathogen challenge, 90% protection was achieved by both strains. All
enzyme activities related to oxidative stress were modified by the two PGPR,
especially APX and SOD upon salinity stress challenge, and APX and GR upon
pathogen presence. Both bacteria induced chitinase activity 24 and 48 h after
pathogen inoculation, and L81 induced beta-1,3-Glucanase activity 48 h after
pathogen inoculation, evidencing the priming effect. These results indicate that
these strains could be used as bio-fortifying agents in biotechnological
inoculants in order to reduce the effects of different stresses, and indirectly
reduce the use of agrochemicals.
PMID- 26439658
TI - The effect of gender on outcomes of aortoiliac artery interventions for
claudication.
AB - OBJECTIVE: To explore the relationship between gender, native artery diameters,
and outcomes of stent revascularization (ST) in the "Claudication: Exercise
versus Endoluminal Revascularization" trial. METHODS: A comparative analysis was
performed of the impact of gender, age, weight, height, body mass index, and body
surface area on revascularization outcomes at baseline and 6months in 55 arterial
segments of aorta, common iliac artery, and external iliac artery (EIA). RESULTS:
Women demonstrated smaller diameter of the EIA. However, the clinical outcomes of
revascularization were not negatively affected by the gender-based differences.
CONCLUSION: Gender-based differences are unlikely to significantly impact outcome
of ST.
PMID- 26439660
TI - Exogenous administration of chronic corticosterone affects hepatic cholesterol
metabolism in broiler chickens showing long or short tonic immobility.
AB - Tonic immobility (TI) is an innate characteristic of animals related to fear or
stress response. Animals can be classified into long TI (LTI) and short TI (STI)
phenotypes based on TI test duration. In this study, effect of TI phenotype,
chronic corticosterone administration (CORT), and their interaction on
cholesterol metabolism in liver was evaluated in broilers. LTI broilers showed
higher level of cholesterol in liver compared to STI chickens (p<0.05), and CORT
significantly increased hepatic cholesterol content (p<0.01). Real-time PCR
results showed that both TI and CORT potentially altered ABCA1 and CYP7A1 gene
expressions (0.0527 years,
of the Tehran Lipid and Glucose Study with complete data on serum creatinine,
cardio-metabolic risk factors, and diet were included for cross-sectional
analysis. After 3 years, 1690 subjects, free of baseline CKD and with complete
follow-up data, were included for longitudinal analysis. Estimated glomerular
filtration rate (eGFR) was calculated using the Modification of Diet in Renal
Disease Study equation and CKD was defined as eGFR < 60 mL/min per 1.73 m(2) .
Dietary intake was collected using a food-frequency questionnaire and SSSDs and
all kinds of fruit juice drinks were combined to estimate the intake of SSBs. To
assess the association of SSBs and CKD, logistic regression adjusted for age,
sex, energy intake, smoking, physical activity, body mass index, sodium,
diabetes, and hypertension were used. RESULTS: The mean age of participants and
serving of SSBs/week were 45.0 years and 2.3, respectively. Compared to
participants taking <0.5 serving/week, consumption of more than four servings of
SSBs and SSSDs per week was associated with increased odds ratio (OR) of
prevalent CKD (1.77 and 2.14, respectively). In longitudinal analyses, the risk
of incident CKD increased by consumption of four servings/week, compared to less
than 0.5 serving/week of SSBs (OR: 1.96; 95% confidence interval (CI):1.23-3.15)
and SSSDs (OR: 2.45; 95% CI:1.55-3.89). CONCLUSION: Consumption of over four
servings per week of SSBs and SSSDs was associated with higher prevalence and
incidence of CKD.
PMID- 26439669
TI - Stable Encapsulated Air Nanobubbles in Water.
AB - The dispersion into water of nanocapsules bearing a highly hydrophobic
fluorinated internal lining yielded encapsulated air nanobubbles. These bubbles,
like their micrometer-sized counterparts (microbubbles), effectively reflected
ultrasound. More importantly, the nanobubbles survived under ultrasonication 100
times longer than a commercial microbubble sample that is currently in clinical
use. We justify this unprecedented stability theoretically. These nanobubbles,
owing to their small size and potential ability to permeate the capillary
networks of tissues, may expand the applications of microbubbles in diagnostic
ultrasonography and find new applications in ultrasound-regulated drug delivery.
PMID- 26439670
TI - International Society on Thrombosis and Haemostasis core curriculum project: core
competencies in clinical thrombosis and hemostasis.
AB - Essentials The priority of ISTH was to establish a global core curriculum in
thrombosis and hemostasis. International survey to determine competencies
required for clinical specialists was carried out in the field. Competency
framework provides a reference point for mapping and developing regional
curricula. Core curriculum informs and links to a variety of ISTH educational
materials. SUMMARY: Background The International Society on Thrombosis and
Haemostasis (ISTH) identified the need for an international core curriculum on
thrombosis and hemostasis for its society members and the larger thrombosis and
hemostasis community. Aims The current research sought consensus on the core
competencies required by medical doctors who are ready to practise as independent
clinical specialists in thrombosis and hemostasis with the aim of developing a
core clinical curriculum for specialists in the field. Method A draft list of
competencies was developed by the Working Group and formed the basis of an online
survey. ISTH members and the larger thrombosis and hemostasis community were
asked to rate the importance of each competency, on a Likert scale, for clinical
specialists in thrombosis and hemostasis. Results There were a total of 644
responses to the online survey with broad geographical representation. There was
general agreement on what level of competency would be required for clinical
specialists in thrombosis and hemostasis at the specified level of training.
Conclusions Using the survey to gain consensus on the level of competency
required by clinical specialists in the field of thrombosis and hemostasis
enabled the development of a core clinical curriculum that has been endorsed by
the ISTH Council. The curriculum will offer a framework and international
reference that will be used by the society, by national and regional
organizations, and for further research.
PMID- 26439671
TI - Assessing the structure and temporal dynamics of seabird communities: the
challenge of capturing marine ecosystem complexity.
AB - Understanding interspecific interactions, and the influences of anthropogenic
disturbance and environmental change on communities, are key challenges in
ecology. Despite the pressing need to understand these fundamental drivers of
community structure and dynamics, only 17% of ecological studies conducted over
the past three decades have been at the community level. Here, we assess the
trophic structure of the procellariiform community breeding at South Georgia, to
identify the factors that determine foraging niches and possible temporal
changes. We collected conventional diet data from 13 sympatric species between
1974 and 2002, and quantified intra- and inter-guild, and annual variation in
diet between and within foraging habits. In addition, we tested the reliability
of stable isotope analysis (SIA) of seabird feathers collected over a 13-year
period, in relation to those of their potential prey, as a tool to assess
community structure when diets are diverse and there is high spatial
heterogeneity in environmental baselines. Our results using conventional diet
data identified a four-guild community structure, distinguishing species that
mainly feed on crustaceans; large fish and squid; a mixture of crustaceans, small
fish and squid; or carrion. In total, Antarctic krill Euphausia superba
represented 32%, and 14 other species a further 46% of the combined diet of all
13 predators, underlining the reliance of this community on relatively few types
of prey. Annual variation in trophic segregation depended on relative prey
availability; however, our data did not provide evidence of changes in guild
structure associated with a suggested decline in Antarctic krill abundance over
the past 40 years. Reflecting the differences in delta(15) N of potential prey
(crustaceans vs. squid vs. fish and carrion), analysis of delta(15) N in chick
feathers identified a three-guild community structure that was constant over a 13
year period, but lacked the trophic cluster representing giant petrels which was
identified using conventional diet data. Our study is the first in recent decades
to examine dietary changes in seabird communities over time. Conventional dietary
analysis provided better resolution of community structure than SIA. However,
delta(15) N in chick feathers, which reflected trophic (level) specialization,
was nevertheless an effective and less time-consuming means of monitoring
temporal changes.
PMID- 26439665
TI - Non-viral therapeutic approaches to ocular diseases: An overview and future
directions.
AB - Currently there are no viable treatment options for patients with debilitating
inherited retinal degeneration. The vast variability in disease-inducing
mutations and resulting phenotypes has hampered the development of therapeutic
interventions. Gene therapy is a logical approach, and recent work has focused on
ways to optimize vector design and packaging to promote optimized expression and
phenotypic rescue after intraocular delivery. In this review, we discuss ongoing
ocular clinical trials, which currently use viral gene delivery, but focus
primarily on new advancements in optimizing the efficacy of non-viral gene
delivery for ocular diseases. Non-viral delivery systems are highly customizable,
allowing functionalization to improve cellular and nuclear uptake, bypassing
cellular degradative machinery, and improving gene expression in the nucleus. Non
viral vectors often yield transgene expression levels lower than viral
counterparts, however their favorable safety/immune profiles and large DNA
capacity (critical for the delivery of large ocular disease genes) make their
further development a research priority. Recent work on particle coating and
vector engineering presents exciting ways to overcome limitations of
transient/low gene expression levels, but also highlights the fact that further
refinements are needed before use in the clinic.
PMID- 26439672
TI - Chondral fracture of the lateral femoral condyle in children with different
treatment methods.
AB - Adolescents are predisposed to chondral injuries of the knee; however, the
incidence of traumatic chondral and osteochondral fractures and their role in the
development of joint degeneration are not fully elucidated. Several methods are
described for the treatment of chondral or osteochondral fractures of the knee.
In our literature review, we could not find any report on the management of
chondral fractures with autologous bone pegs or headless screws. We report three
cases of traumatic cartilage fractures of the lateral femoral condyle in
adolescents who were treated with three different methods. We also present their
follow-up outcomes.
PMID- 26439673
TI - Two follistatin-like 1 homologs are differentially expressed in adult tissues and
during embryogenesis in grass carp (Ctenopharyngodon idellus).
AB - Follistatin-like 1 (Fstl1) peptides play important roles in inhibiting myoblast
proliferation and differentiation. Here, we characterized and examined the
expression patterns of fstl1a and -b in grass carp (Ctenopharyngodon idellus).
These genes encode 314 aa and 310 aa peptides, respectively, sharing a sequence
identity of 83%. Except for the existence of the follistatin-N-terminal (FOLN)
and Kazal-type 2 serine protease inhibitor (Kazal 2) domains, grass carp Fstl1a
and -b do not share amino acid sequence similarity with Fst1 and -b. Both fstl1a
and -b mRNAs were widely expressed in adult tissues. During embryogenesis, grass
carp fstl1a and -b mRNA was detected in the presomitic mesoderm and somites at
12h post fertilization (hpf). At 24hpf, fstl1a mRNA was expressed in the
hindbrain, somites, notochord and tailbud, while fstl1b mRNA was only detected in
the tailbud. At 36hpf, fstl1a mRNA was detected in the hindbrain and notochord,
and fstl1b was also expressed in the notochord. Furthermore, fstl1a and -b were
downregulated in brain and liver tissue following injection with 10 or 50MUg hGH,
while fstl1b was significantly up-regulated in muscle tissue after 10MUg hGH
treatment. Both fstl1a and -b were significantly up-regulated at 2, 4 or 6days of
nutrient restriction, and fstl1a was still highly expressed in the liver and
muscle after 3days of refeeding, as was fstl1b in the brain and muscle. The
expression of these genes returned to near control levels following 6days of
refeeding. Our findings suggest that the two fstls play important but divergent
roles in embryonic development and tissue growth regulation in grass carp.
PMID- 26439674
TI - Cognitive-behavioral therapy for sleep disturbances in treating posttraumatic
stress disorder symptoms: A meta-analysis of randomized controlled trials.
AB - Sleep disturbances are frequently reported in patients with posttraumatic stress
disorder (PTSD). There is evidence that sleep disturbance is not only a secondary
symptom but also a risk factor for PTSD. Sleep-specific psychological treatments
provide an alternative to conventional trauma-focused psychological treatments.
The current meta-analysis evaluated the efficacy of sleep-specific cognitive
behavioral therapy (CBT) in mitigating PTSD, sleep, and depressive symptoms. A
total of 11 randomized controlled trials were included in the meta-analytic
comparisons between sleep-specific CBT and waiting-list control groups at
posttreatment. Random effects models showed significant reduction in self-report
PTSD and depressive symptoms and insomnia severity in the sleep-specific CBT
group. The corresponding effect sizes, measured in Hedges' g, were 0.58, 0.44,
and 1.15, respectively. The effect sizes for sleep diary-derived sleep onset
latency, wake after sleep onset, and sleep efficiency were 0.83, 1.02 and 1.15,
respectively. The average study attrition rate of sleep-specific CBT was
relatively low (12.8%), with no significant difference from the control group
(9.4%). In conclusion, sleep-specific CBT appears to be efficacious and feasible
in treating PTSD symptoms. Due to the relatively small number of randomized
controlled trials available, further research is warranted to confirm its
efficacy and acceptability, especially in comparison to trauma-specific
psychological treatments.
PMID- 26439675
TI - Temperate phages promote colicin-dependent fitness of Salmonella enterica serovar
Typhimurium.
AB - Bacteria employ bacteriocins for interference competition in microbial
ecosystems. Colicin Ib (ColIb), a pore-forming bacteriocin, confers a significant
fitness benefit to Salmonella enterica serovar Typhimurium (S. Tm) in competition
against commensal Escherichia coli in the gut. ColIb is released from S. Tm into
the environment, where it kills susceptible competitors. However, colicin
specific release proteins, as they are known for other colicins, have not been
identified in case of ColIb. Thus, its release mechanism has remained unclear. In
the current study, we have established a new link between ColIb release and lysis
activity of temperate, lambdoid phages. By the use of phage-cured S. Tm mutant
strains, we show that the presence of temperate phages and their lysis genes is
necessary and sufficient for release of active ColIb into the culture
supernatant. Furthermore, phage-mediated lysis significantly enhanced S. Tm
fitness in competition against a ColIb-susceptible competitor. Finally,
transduction with the lambdoid phage 933W rescued the defect of E. coli strain
MG1655 with respect to ColIb release. In conclusion, ColIb is released from
bacteria in the course of phage lysis. Our data reveal a new mechanism for
colicin release and point out a novel function of temperate phages in enhancing
colicin-dependent bacterial fitness.
PMID- 26439676
TI - A Survey of the Impact of Deyolking on Biological Processes Covered by Shotgun
Proteomic Analyses of Zebrafish Embryos.
AB - Deyolking, the removal of the most abundant protein from the zebrafish (Danio
rerio) embryo, is a common technique for in-depth exploration of proteome-level
changes in vivo due to various environmental stressors or pharmacological impacts
during embryonic stage of development. However, the effect of this procedure on
the remaining proteome has not been fully studied. Here, we report a label-free
shotgun proteomics survey on proteome coverage and biological processes that are
enriched and depleted as a result of deyolking. Enriched proteins are involved in
cellular energetics and development pathways, specifically implicating enrichment
related to mitochondrial function. Although few proteins were removed completely
by deyolking, depleted molecular pathways were associated with calcium signaling
and signaling events implicating immune system response.
PMID- 26439677
TI - Hexagonal Boron Nitride-Graphene Heterostructures: Synthesis and Interfacial
Properties.
AB - Research on in-plane and vertically-stacked heterostructures of graphene and
hexagonal boron nitride (h-BN) have attracted intense attentions for energy band
engineering and device performance optimization of graphene. In this review
article, recent advances in the controlled syntheses, interfacial structures, and
electronic properties, as well as novel device constructions of h-BN and graphene
heterostructures are highlighted. Firstly, diverse synthesis approaches for in
plane h-BN and graphene (h-BN-G) heterostructures are reviewed, and their
applications in nanoelectronics are briefly introduced. Moreover, the interfacial
structures and electronic properties of h-BN-G heterojunctions are discussed, and
a zigzag type interface is found to preferentially evolve at the linking edge of
the two structural analogues. Secondly, several synthetic routes for the
vertically-stacked graphene/h-BN (G/h-BN) heterostructures are also reviewed. The
role of h-BN as perfect dielectric layers in promoting the device performance of
graphene is presented. Finally, future research directions in the synthesis and
application of such heterostructures are discussed.
PMID- 26439678
TI - How will the semi-natural vegetation of the UK have changed by 2030 given likely
changes in nitrogen deposition?
AB - Nitrogen deposition is known to have major impacts on contemporary ecosystems but
few studies have addressed how these impacts will develop over coming decades. We
consider likely changes to British semi-natural vegetation up to the year 2030
both qualitatively, based on knowledge of species responses from experimental and
gradient studies, and quantitatively, based on modelling of species relationships
in national monitoring data. We used historical N deposition trends and national
predictions of changing deposition to calculate cumulative deposition from 1900
to 2030. Data from the Countryside Survey (1978, 1990 and 1998) was used to
parameterise models relating cumulative N deposition to Ellenberg N which were
then applied to expected future deposition trends. Changes to habitat suitability
for key species of grassland, heathland and bog, and broadleaved woodland to 2030
were predicted using the MultiMOVE model. In UK woodlands by 2030 there is likely
to be reduced occurrence of lichens, increased grass cover and a shift towards
more nitrophilic vascular plant species. In grasslands we expect changing species
composition with reduced occurrence of terricolous lichens and, at least in acid
grasslands, reduced species richness. In heaths and bogs we project overall
reductions in species richness with decreased occurrence of terricolous lichens
and some bryophytes, reduced cover of dwarf shrubs and small increases in
grasses. Our study clearly suggests that changes in vegetation due to nitrogen
deposition are likely to continue through coming decades.
PMID- 26439679
TI - Correlation between electromyography and quantitative ultrasonography of facial
muscles in patients with facial palsy.
AB - INTRODUCTION: In this study we correlated results of ultrasonographic muscle
thickness and contractility with facial electromyography (EMG) in patients with
unilateral peripheral acute or chronic facial palsy. METHODS: Two hundred twenty
measurements of 4 facial muscles (frontalis, orbicularis oculi, zygomaticus, and
orbicularis oris) were performed in 44 patients. RESULTS: Facial muscle thickness
at rest and during muscle contraction correlated best with EMG insertional
activity, and facial muscle contractility correlated with EMG voluntary activity.
The correlation was much higher at >14 days after onset of facial palsy. The
orbicularis oris, followed by the frontalis muscle, showed the best correlation
between ultrasound and EMG. CONCLUSIONS: Quantitative ultrasound of facial
muscles helps confirm the results of facial EMG and is of particular additional
value in the first 14 days after onset when the reliability of EMG is low.
PMID- 26439680
TI - Development and preliminary evaluation of a genomewide single nucleotide
polymorphisms resource generated by RAD-seq for the small yellow croaker
(Larimichthys polyactis).
AB - Recent advances in high-throughput sequencing technologies have offered the
possibility to generate genomewide sequence data to delineate previously
unidentified genetic structure, obtain more accurate estimates of demographic
parameters and to evaluate potential adaptive divergence. Here, we identified 27
556 single nucleotide polymorphisms for the small yellow croaker (Larimichthys
polyactis) using restriction-site-associated DNA (RAD) sequencing of 24
individuals from two populations. Significant sources of genetic variation were
identified, with an average nucleotide diversity (pi) of 0.00105 +/- 0.000425
across individuals, and long-term effective population size was thus estimated to
range between 26 172 and 261 716. According to the results, no differentiation
between the two populations was detected based on the SNP data set of top quality
score per contig or neutral loci. However, the two analysed populations were
highly differentiated based on SNP data set of both top FST value per contig and
the outlier SNPs. Moreover, local adaptation was highlighted by an FST -based
outlier tests implemented in LOSITAN and a total of 538 potentially locally
selected SNPs were identified. blast2go annotation of contigs containing the
outlier SNPs yielded hits for 37 (66%) of 56 significant blastx matches.
Candidate genes for local adaptation constituted a wide array of biological
functions, including cellular response to oxidative stress, actin filament
binding, ion transmembrane transport and synapse assembly. The generated SNP
resources in this study provided a valuable tool for future population genetics
and genomics studies of L. polyactis.
PMID- 26439681
TI - Flavonoids of Korean Citrus aurantium L. Induce Apoptosis via Intrinsic Pathway
in Human Hepatoblastoma HepG2 Cells.
AB - Korean Citrus aurantium L. has long been used as a medicinal herb for its anti
inflammatory, antioxidant, and anticancer properties. The present study
investigates the anticancer role of flavonoids extracted from C. aurantium on
human hepatoblastoma cell, HepG2. The Citrus flavonoids inhibit the proliferation
of HepG2 cells in a dose-dependent manner. This result was consistent with the in
vivo xenograft results. Apoptosis was detected by cell morphology, cell cycle
analysis, and immunoblot. Flavonoids decreased the level of pAkt and other
downstream targets of phosphoinositide-3-kinase/Akt pathway - P-4EBP1 and P
p70S6K. The expressions of cleaved caspase 3, Bax, and Bak were increased, while
those of Bcl-2 and Bcl-xL were decreased with an increase in the expression of
Bax/Bcl-xL ratio in treated cells. Loss of mitochondrial membrane potential was
also observed in flavonoid-treated HepG2 cells. It was also observed that the P
p38 protein level was increased both dose and time dependently in flavonoid
treated cells. Collectively, these results suggest that flavonoid extracted from
Citrus inhibits HepG2 cell proliferation by inducing apoptosis via an intrinsic
pathway. These findings suggest that flavonoids extracted from C. aurantium L.
are potential chemotherapeutic agents against liver cancer.
PMID- 26439682
TI - p21 upregulation in hair follicle stem cells is associated with telogen retention
in aged mice.
PMID- 26439683
TI - Automated prognostic pattern detection shows favourable diffuse pattern of
FOXP3(+) Tregs in follicular lymphoma.
AB - BACKGROUND: Histopathological prognostication relies on morphological pattern
recognition, but as numbers of biomarkers increase, human prognostic pattern
recognition ability decreases. Follicular lymphoma (FL) has a variable outcome,
partly determined by FOXP3 Tregs. We have developed an automated method,
hypothesised interaction distribution (HID) analysis, to analyse spatial patterns
of multiple biomarkers which we have applied to tumour-infiltrating lymphocytes
in FL. METHODS: A tissue microarray of 40 patient samples was used in triplex
immunohistochemistry for FOXP3, CD3 and CD69, and multispectral imaging used to
determine the numbers and locations of CD3(+), FOXP3/CD3(+) and CD69/CD3(+) T
cells. HID analysis was used to identify associations between cellular pattern
and outcome. RESULTS: Higher numbers of CD3(+) (P=0.0001), FOXP3/CD3(+)
(P=0.0031) and CD69/CD3(+) (P=0.0006) cells were favourable. Cross-validated HID
analysis of cell pattern identified patient subgroups with statistically
significantly different survival (35.5 vs 142 months, P=0.00255), a more diffuse
pattern associated with favourable outcome and an aggregated pattern with
unfavourable outcome. CONCLUSIONS: A diffuse pattern of FOXP3 and CD69 positivity
was favourable, demonstrating ability of HID analysis to automatically identify
prognostic cellular patterns. It is applicable to large numbers of biomarkers,
representing an unsupervised, automated method for identification of undiscovered
prognostic cellular patterns in cancer tissue samples.
PMID- 26439684
TI - HIF2alpha is involved in the expansion of CXCR4-positive cancer stem-like cells
in renal cell carcinoma.
AB - BACKGROUND: Hypoxia and the subsequent activation of hypoxia-inducible factor
2alpha (HIF2alpha) contribute to the progression of a variety of cancers.
However, their role in the generation of renal cell carcinoma-derived stem cells
has not been fully addressed. METHODS: A sphere formation assay, cell
proliferation, RT-PCR, western blot, FACS, immunohistochemistry and tumour
xenograft were used to study the role of HIF2alpha. RESULTS: Propagation of four
renal cell carcinoma (RCC) cell lines (Caki-1, Caki-2, 786-O, 769-P) in anchorage
independent floating spheres led to the expansion of cells bearing the CXCR4
(CD184) surface marker. Inhibition of the CXCR4 pathway reduced sphere expansion.
The enhanced self-renewal activity of the CXCR4-positive spheres was preceded by
the upregulation of HIF2alpha. Knockdown of HIF2alpha abrogated CXCR4 expression
and sphere formation. Finally, RCC-derived spheres showed an undifferentiated
phenotype in vivo and formed subcutaneous tumours that highly expressed HIF2alpha
and CXCR4. Inhibition of HIF2alpha abolished tumour growth in animal models.
CONCLUSIONS: These results suggest that the generation of RCC-derived CSCs
involves the activation of HIF2alpha and may provide a foundation for the
development of new strategies to prevent the induction of CSCs in RCC.
PMID- 26439685
TI - Prediction of coronary artery disease risk based on multiple longitudinal
biomarkers.
AB - In the last decade, few topics in the area of cardiovascular disease (CVD)
research have received as much attention as risk prediction. One of the well
documented risk factors for CVD is high blood pressure (BP). Traditional CVD risk
prediction models consider BP levels measured at a single time and such models
form the basis for current clinical guidelines for CVD prevention. However, in
clinical practice, BP levels are often observed and recorded in a longitudinal
fashion. Information on BP trajectories can be powerful predictors for CVD
events. We consider joint modeling of time to coronary artery disease and
individual longitudinal measures of systolic and diastolic BPs in a primary care
cohort with up to 20 years of follow-up. We applied novel prediction metrics to
assess the predictive performance of joint models. Predictive performances of
proposed joint models and other models were assessed via simulations and
illustrated using the primary care cohort.
PMID- 26439686
TI - Characterization of adipose-derived stem cells from subcutaneous and visceral
adipose tissues and their function in breast cancer cells.
AB - Adipose-derived stem cells are capable of differentiating into multiple cell
types and thus considered useful for regenerative medicine. However, this
differentiation feature seems to be associated with tumor initiation and
metastasis raising safety concerns, which requires further investigation. In this
study, we isolated adipose-derived stem cells from subcutaneous as well as from
visceral adipose tissues of the same donor and systematically compared their
features. Although being characteristic of mesenchymal stem cells, subcutaneous
adipose-derived stem cells tend to be spindle form-like and are more able to home
to cancer cells, whereas visceral adipose-derived stem cells incline to be
"epithelial"-like and more competent to differentiate. Moreover, compared to
subcutaneous adipose-derived stem cells, visceral adipose-derived stem cells are
more capable of promoting proliferation, inducing the epithelial-to-mesenchymal
transition, enhancing migration and invasion of breast cancer cells by cell-cell
contact and by secreting interleukins such as IL-6 and IL-8. Importantly, ASCs
affect the low malignant breast cancer cells MCF-7 more than the highly
metastatic MDA-MB-231 cells. Induction of the epithelial-to-mesenchymal
transition is mediated by the activation of multiple pathways especially the
PI3K/AKT signaling in breast cancer cells. BCL6, an important player in B-cell
lymphoma and breast cancer progression, is crucial for this transition. Finally,
this transition fuels malignant properties of breast cancer cells and render them
resistant to ATP competitive Polo-like kinase 1 inhibitors BI 2535 and BI 6727.
PMID- 26439687
TI - RASSF8 downregulation promotes lymphangiogenesis and metastasis in esophageal
squamous cell carcinoma.
AB - Lymphatic vessels are the major routes of human esophageal squamous cell
carcinoma (ESCC) metastasis. Tumor cells secrete pro-lymphangiogenic factors to
induce new lymphatic vessels, promoting lymph node metastasis. In this study, we
show that RAS association domain family 8 (RASSF8) expression in ESCC clinical
samples was inversely correlated with lymph node metastasis and patients
survival. Tumor cells with low RASSF8 expression had higher apparent migratory
ability, and promoted and lymphangiogenesis both in vitro and in vivo. RASSF8
downregulation enhanced VEGF-C expression and caused subcellular redistribution
of p65 in ESCC. Our results show that RASSF8 acts as a tumor suppressor in ESCC
and is a potential therapeutic target for preventing lymph node metastasis.
PMID- 26439688
TI - miRNA interventions serve as 'magic bullets' in the reversal of glioblastoma
hallmarks.
AB - microRNAs (miRNAs) are no longer deemed small pieces of RNA "trash" in the human
transcriptome but are considered to be master regulators of gene expression that
are critical in maintaining cellular homeostasis post-transcriptionally. The
concept triggers great interest in studying miRNA dysregulations in human
diseases, especially in cancers. Glioblastoma (GBM) has long been the leading
cause of the high mortality and morbidity of CNS tumors in adults, which is a
consequence of the lack of strategies to reverse the hallmark features of GBM
(e.g., borderless expansion and diffuse infiltration). In the past decade,
dissecting the molecular architecture of GBM has led to a better understanding of
the molecular basis of the hallmarks, generating many promising pharmacological
protein targets. However, few clinical responses have been highlighted,
suggesting the demand for new therapeutic strategies and targets. In this review,
we systemically summarize the context-dependently validated miRNAs with one or
more functional targets in the development of GBM hallmarks and review the
current miRNA-targeting strategies. We note that only a few miRNA-based
therapeutics are trialed for clinical significance, and none of them is tailored
to GBM, thereby urging us to bring miRNA therapeutics to the front line either
alone or in combination.
PMID- 26439689
TI - Vascular heterogeneity and targeting: the role of YKL-40 in glioblastoma
vascularization.
AB - Malignant glioblastomas (GBM) are highly malignant brain tumors that have
extensive and aberrant tumor vasculature, including multiple types of vessels.
This review focuses on recent discoveries that the angiogenic factor YKL-40
(CHI3L1) acts on glioblastoma-stem like cells (GSCs) to drive the formation of
two major forms of tumor vascularization: angiogenesis and vasculogenic mimicry
(VM). GSCs possess multipotent cells able to transdifferentiate into vascular
pericytes or smooth muscle cells (PC/SMCs) that either coordinate with
endothelial cells (ECs) to facilitate angiogenesis or assemble in the absence of
ECs to form blood-perfused channels via VM. GBMs express high levels of YKL-40
that drives the divergent signaling cascades to mediate the formation of these
distinct microvascular circulations. Although a variety of anti-tumor agents that
target angiogenesis have demonstrated transient benefits for patients, they often
fail to restrict tumor growth, which underscores the need for additional
therapeutic tools. We propose that targeting YKL-40 may compliment conventional
anti-angiogenic therapies to provide a substantial clinical benefit to patients
with GBM and several other types of solid tumors.
PMID- 26439690
TI - Genetic variations of body weight and GCRV resistance in a random mating
population of grass carp.
AB - The grass carp (Ctenopharyngodon idellus) is an important species in freshwater
aquaculture both in China and on a global scale. Variety degeneration and
frequent diseases have limited the further development of grass carp aquaculture.
Thus, new and improved varieties are required. Here, we identified and assessed
the body weight and disease resistance in a random mating population of 19 a?? *
22 a?? grass carp, which were derived from different water systems. In both the
growth experimental group of 10,245 fish and grass carp reovirus (GCRV)-infected
group with 10,000 fish, 78 full-sib families were statistically analyzed for body
weight and GCRV resistance. The findings showed that body weight traits had low
heritability (0.11 +/- 0.04, 0.10 +/- 0.03 and 0.12 +/- 0.05), GCRV resistance
traits had high heritability (0.63 +/- 0.11); body weight was higher in 3
families, whereas GCRV resistance was significantly greater in 11 families. Our
results confirmed that the natural germplasm resources of wild grass carp were
genetically diverse. Breeding of GCRV resistant varieties of grass carp have
better genetic basis. This study provides the basis for constructing basal
populations for grass carp selective breeding, quantitative trait loci (QTL) and
genome-wide association studies (GWAS) analysis.
PMID- 26439691
TI - Aging with ING: a comparative study of different forms of stress induced
premature senescence.
AB - Cell senescence contributes to organismal aging and is induced by telomere
erosion and an ensuing DNA damage signal as cells reach the end of their
replicative lifespan in vitro or in vivo. Stresses induced by oncogene or tumor
suppressor hyperactivation, oxidative stress, ionizing radiation and other DNA
damaging agents result in forms of stress induced premature senescence (SIPS)
that show similarities to replicative senescence. Since replicative senescence
and SIPS occur over many days and many population doublings of the mass cultures
of primary cells used to study senescence, the sequence of events that occur
downstream of senescence signaling can be challenging to define. Here we compare
a new model of ING1a-induced senescence with several other forms of senescence.
The ING1a epigenetic regulator synchronously induces senescence in mass cultures
several-fold faster than all other agents, taking 24 and 36 hours to activate the
Rb/ p16INK4a, but not the p53 tumor suppressor axis to efficiently induce
senescence. ING1a induces expression of intersectin 2, a scaffold protein
necessary for endocytosis, altering the stoichiometry of endocytosis proteins,
subsequently blocking growth factor uptake leading to activation of Rb signaling
to block cell growth. ING1a acts as a novel link in the activation of the Rb
pathway that can impose senescence in the absence of activating p53-mediated DNA
damage signaling, and should prove useful in defining the molecular events
contributing to Rb-induced senescence.
PMID- 26439692
TI - Characterisation of inflammatory processes in Helicobacter pylori-induced gastric
lymphomagenesis in a mouse model.
AB - Gastric MALT lymphoma (GML) can be induced by Helicobacter pylori infection in
BALB/c mice thymectomised at day 3 post-birth (d3Tx). This represented a unique
opportunity to investigate the inflammatory process involved in the recruitment,
proliferation and structuration of lymphoid infiltrates in the gastric mucosa of
mice developing GML. Complementary molecular and proteomic approaches
demonstrated that Th1 and Th2 cytokines were upregulated, along with
activators/regulators of the lymphoid response and numerous chemokines.
Interleukin-4, interferon gamma, lymphotoxin-alpha and -beta were significantly
upregulated and correlated with the inflammatory scores for all the d3Tx mice.
GML lesions in d3Tx mice infected with H. pylori were associated with the
presence of the inflammatory response. The dysregulation of numerous members of
the tumour necrosis factor superfamily was also evident and suggests that they
could play an important role in GML pathology, especially in light of their
ability to promote and control lymphocyte proliferation.
PMID- 26439693
TI - Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer
cell lines and patient derived xenografts.
AB - BACKGROUND: CRC is a significant cause of cancer mortality, and new therapies are
needed for patients with advanced disease. TAK-733 is a highly potent and
selective investigational novel MEK allosteric site inhibitor. MATERIALS AND
METHODS: In a preclinical study of TAK-733, a panel of CRC cell lines were
exposed to varying concentrations of the agent for 72 hours followed by a
sulforhodamine B assay. Twenty patient-derived colorectal cancer xenografts were
then treated with TAK-733 in vivo. Tumor growth inhibition index (TGII) was
assessed to evaluate the sensitivity of the CRC explants to TAK-733 while linear
regression was utilized to investigate the predictive effects of genotype on the
TGII of explants. RESULTS: Fifty-four CRC cell lines were exposed to TAK-733,
while 42 cell lines were deemed sensitive across a broad range of mutations.
Eighty-two percent of the cell lines within the sensitive subset were BRAF or
KRAS/NRAS mutant, whereas 80% of the cell lines within the sensitive subset were
PIK3CA WT. Twenty patient-derived human tumor CRC explants were then treated with
TAK-733. In total, 15 primary human tumor explants were found to be sensitive to
TAK-733 (TGII <= 20%), including 9 primary human tumor explants that exhibited
tumor regression (TGII > 100%). Explants with a BRAF/KRAS/NRAS mutant and PIK3CA
wild-type genotype demonstrated increased sensitivity to TAK-733 with a median
TGII of -6%. MEK-response gene signatures also correlated with responsiveness to
TAK-733 in KRAS-mutant CRC. CONCLUSIONS: The MEK inhibitor TAK-733 demonstrated
robust antitumor activity against CRC cell lines and patient-derived tumor
explants. While the preclinical activity observed in this study was considerable,
single-agent efficacy in the clinic has been limited in CRC, supporting the use
of these models in an iterative manner to elucidate resistance mechanisms that
can guide rational combination strategies.
PMID- 26439694
TI - Comprehensive cancer-gene panels can be used to estimate mutational load and
predict clinical benefit to PD-1 blockade in clinical practice.
AB - Cancer gene panels (CGPs) are already used in clinical practice to match tumor's
genetic profile with available targeted therapies. We aimed to determine if CGPs
could also be applied to estimate tumor mutational load and predict clinical
benefit to PD-1 and CTLA-4 checkpoint blockade therapy. Whole-exome sequencing
(WES) mutation data obtained from melanoma and non-small cell lung cancer (NSCLC)
patients published by Snyder et al. 2014 and Rizvi et al. 2015, respectively,
were used to select nonsynonymous somatic mutations occurring in genes included
in the Foundation Medicine Panel (FM-CGP) and in our own Institutional Panel (HSL
CGP). CGP-mutational load was calculated for each patient using both panels and
was associated with clinical outcomes as defined and reported in the original
articles. Higher CGP-mutational load was observed in NSCLC patients presenting
durable clinical benefit (DCB) to PD-1 blockade (FM-CGP P=0.03, HSL-CGP P=0.01).
We also observed that 69% of patients with high CGP-mutational load experienced
DCB to PD-1 blockade, as compared to 20% of patients with low CGP-mutational load
(FM-CGP and HSL-CGP P=0.01). Noteworthy, predictive accuracy of CGP-mutational
load for DCB was not statistically different from that estimated by WES
sequencing (P=0.73). Moreover, a high CGP-mutational load was significantly
associated with progression-free survival (PFS) in patients treated with PD-1
blockade (FM-CGP P=0.005, HR 0.27, 95% IC 0.105 to 0.669; HSL-CGP P=0.008, HR
0.29, 95% IC 0.116 to 0.719). Similar associations between CGP-mutational load
and clinical benefit to CTLA-4 blockade were not observed. In summary, our data
reveals that CGPs can be used to estimate mutational load and to predict clinical
benefit to PD-1 blockade, with similar accuracy to that reported using WES.
PMID- 26439695
TI - Remarkable similarities of chromosomal rearrangements between primary human
breast cancers and matched distant metastases as revealed by whole-genome
sequencing.
AB - To better understand and characterize chromosomal structural variation during
breast cancer progression, we enumerated chromosomal rearrangements for 11
patients by performing low-coverage whole-genome sequencing of 11 primary breast
tumors and their 13 matched distant metastases. The tumor genomes harbored a
median of 85 (range 18-404) rearrangements per tumor, with a median of 82 (26
310) in primaries compared to 87 (18-404) in distant metastases. Concordance
between paired tumors from the same patient was high with a median of 89% of
rearrangements shared (range 61-100%), whereas little overlap was found when
comparing all possible pairings of tumors from different patients (median 3%).
The tumors exhibited diverse genomic patterns of rearrangements: some carried
events distributed throughout the genome while others had events mostly within
densely clustered chromothripsis-like foci at a few chromosomal locations.
Irrespectively, the patterns were highly conserved between the primary tumor and
metastases from the same patient. Rearrangements occurred more frequently in
genic areas than expected by chance and among the genes affected there was
significant enrichment for cancer-associated genes including disruption of TP53,
RB1, PTEN, and ESR1, likely contributing to tumor development. Our findings are
most consistent with chromosomal rearrangements being early events in breast
cancer progression that remain stable during the development from primary tumor
to distant metastasis.
PMID- 26439696
TI - Cx26 knockout predisposes the mammary gland to primary mammary tumors in a DMBA
induced mouse model of breast cancer.
AB - Down-regulation of the gap junction protein connexin26 (Cx26) is an early event
following breast cancer onset and has led to Cx26 being classically described as
a tumor suppressor. Interestingly, mutations in theCx26 gene (GJB2) reduce or
ablate Cx26 gap junction channel function and are the most common cause of
genetic deafness. It is unknown if patients with loss-of-function GJB2 mutations
have a greater susceptibility to breast tumorigenesis or aggressive breast cancer
progression. To investigate these possibilities, 7, 12
dimethylbenz[alpha]anthracene (DMBA)-induced tumor development was evaluated in
BLG-Cre; Cx26fl/fl mice expressing Cre under the beta-Lactoglobulin promoter
(Cre+) compared to Cx26fl/fl controlmice (Cre-) following pituitary isograft
driven Cx26 knockout. A significantly increased number of DMBA-treated Cre+ mice
developed primary mammary tumors, as well as developed multiple tumors, compared
to Cre- mice. Primary tumors of Cre+ mice were of multiple histological subtypes
and had similar palpable tumour onset and growth rate compared to tumors from Cre
mice. Lungs were evaluated for evidence of metastases revealing a similar
percentage of lung metastases in Cre+ and Cre- mice. Together, our results
suggest that loss of Cx26 predisposes the mammary gland to chemically induced
mammary tumour formation which may have important implications to patients with
GJB2 mutations.
PMID- 26439697
TI - Characterization of a mantle cell lymphoma cell line resistant to the Chk1
inhibitor PF-00477736.
AB - Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by the
chromosomal translocation t(11;14) that leads to constitutive expression of
cyclin D1, a master regulator of the G1-S phase. Chk1 inhibitors have been
recently shown to be strongly effective as single agents in MCL. To investigate
molecular mechanisms at the basis of Chk1 inhibitor activity, a MCL cell line
resistant to the Chk1 inhibitor PF-00477736 (JEKO-1 R) was obtained and
characterized. The JEKO-1 R cell line was cross resistant to another Chk1
inhibitor (AZD-7762) and to the Wee1 inhibitor MK-1775. It displayed a shorter
doubling time than parental cell line, likely due to a faster S phase. Cyclin D1
expression levels were decreased in resistant cell line and its re-overexpression
partially re-established PF-00477736 sensitivity. Gene expression profiling
showed an enrichment in gene sets involved in pro-survival pathways in JEKO-1 R.
Dasatinib treatment partly restored PF-00477736 sensitivity in resistant cells
suggesting that the pharmacological interference of pro-survival pathways can
overcome the resistance to Chk1 inhibitors. These data further corroborate the
involvement of the t(11;14) in cellular sensitivity to Chk1 inhibitors, fostering
the clinical testing of Chk1 inhibitors as single agents in MCL.
PMID- 26439698
TI - PPE26 induces TLR2-dependent activation of macrophages and drives Th1-type T-cell
immunity by triggering the cross-talk of multiple pathways involved in the host
response.
AB - The pathophysiological functions and the underlying molecular basis of PE /PPE
proteins of M. tuberculosis remain largely unknown. In this study, we focused on
the link between PPE26 and host response. We demonstrated that PPE26 can induce
extensive inflammatory responses in macrophages through triggering the cross-talk
of multiple pathways involved in the host response, as revealed by iTRAQ-based
subcellular quantitative proteomics. We observed that PPE26 is able to
specifically bind to TLR2 leading to the subsequent activation of MAPKs and NF
kappaB signaling. PPE26 functionally stimulates macrophage activation by
augmenting pro-inflammatory cytokine production (TNF-alpha, IL-6 and IL-12 p40)
and the expression of cell surface markers (CD80, CD86, MHC class I and II). We
observed that PPE26-treated macrophages effectively polarizes naive CD4(+) T
cells to up-regulate CXCR3 expression, and to secrete IFN-gamma and IL-2,
indicating PPE26 contributes to the Th1 polarization during the immune response.
Importantly, rBCG::PPE26 induces stronger antigen-specific TNF-alpha and IFN
gamma activity, and higher levels of the Th1 cytokines TNF-alpha and IFN-gamma
comparable to BCG. Moreover, PPE26 effectively induces the reciprocal expansion
of effector/memory CD4(+)/CD8(+) CD44(high)CD62L(low) T cells in the spleens of
mice immunized with this strain. These results suggest that PPE26 may be a TLR2
agonist that stimulates innate immunity and adaptive immunity, indicating that
PPE26 is a potential antigen for the rational design of an efficient vaccine
against M. tuberculosis.
PMID- 26439701
TI - Switchable Opening and Closing of a Liquid Marble via Ultrasonic Levitation.
AB - Liquid marbles have promising applications in the field of microreactors, where
the opening and closing of their surfaces plays a central role. We have levitated
liquid water marbles using an acoustic levitator and, thereby, achieved the
manipulation of the particle shell in a controlled manner. Upon increasing the
sound intensity, the stable levitated liquid marble changes from a quasi-sphere
to a flattened ellipsoid. Interestingly, a cavity on the particle shell can be
produced on the polar areas, which can be completely healed when decreasing the
sound intensity, allowing it to serve as a microreactor. The integral of the
acoustic radiation pressure on the part of the particle surface protruding into
air is responsible for particle migration from the center of the liquid marble to
the edge. Our results demonstrate that the opening and closing of the liquid
marble particle shell can be conveniently achieved via acoustic levitation,
opening up a new possibility to manipulate liquid marbles coated with non
ferromagnetic particles.
PMID- 26439699
TI - Piperine metabolically regulates peritoneal resident macrophages to potentiate
their functions against bacterial infection.
AB - Pepper, a daily-used seasoning for promoting appetite, is widely used in folk
medicine for treating gastrointestinal diseases. Piperine is the major alkaloid
in pepper and possesses a wide range of pharmacological activities. However, the
mechanism for linking metabolic and medicinal activities of piperine remains
unknown. Here we report that piperine robustly boosts mTORC1 activity by
recruiting more system L1 amino acid transporter (SLC7A5/SLC3A2) to the cell
membrane, thus promoting amino acid metabolism. Piperine-induced increase of
mTORC1 activity in resident peritoneal macrophages (pMPhis) is correlated with
enhanced production of IL-6 and TNF-alpha upon LPS stimulation. Such an
enhancement of cytokine production could be abrogated by inhibitors of the mTOR
signaling pathway, indicating mTOR's action in this process. Moreover, piperine
treatment protected resident pMPhis from bacterium-induced apoptosis and
disappearance, and increased their bacterial phagocytic ability. Consequently,
piperine administration conferred mice resistance against bacterial infection and
even sepsis. Our data highlight that piperine has the capacity to metabolically
reprogram peritoneal resident macrophages to fortify their innate functions
against bacterial infection.
PMID- 26439700
TI - S-1 plus cisplatin versus fluorouracil plus cisplatin in advanced gastric or
gastro-esophageal junction adenocarcinoma patients: a pilot study.
AB - The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer
patients in first line setting is unknown. In this pilot study, patients with
advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and
randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU
plus cisplatin (CF group). The primary endpoint was time to progression (TTP).
Secondary end points included overall survival (OS) and safety. This study was
registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients
were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months
in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394,
p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR
1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse
events in both groups were anemia, leukopenia, neutropenia, nausea,
thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus
cisplatin is an effective and tolerable option for advanced gastric or gastro
esophageal junction adenocarcinoma patients in China.
PMID- 26439703
TI - Visible-Light-Induced Activity Control of Peroxidase Bound to Fe-Doped Titanate
Nanosheets with Nanometric Lateral Dimensions.
AB - Catalytic performance of horseradish peroxidase (HRP) electrostatically adsorbed
on nanometric and semiconducting Fe-doped titanate (FT) nanosheets was
successfully manipulated by visible light illumination. A colloidal solution of
FT with a narrow band gap corresponding to a visible light region was fabricated
through a hydrolysis reaction of metals sources. HRP could be easily bound to the
FT at pH = 4 through an electrostatic interaction between them, and the formed
HRP-FT was utilized for the visible-light-driven enzymatic reaction. Under
exposure to visible light with enough energy for band gap excitation of the FT,
catalytic activity of HRP-FT was dramatically enhanced as compared with free
(unbound) HRP and was simply adjusted by light intensity. In addition, wavelength
dependence of an enzymatic reaction rate was analogous to an optical absorption
spectrum of the FT. These results substantiated an expected reaction mechanism in
which the photoenzymatic reaction was initiated by band gap excitation of FT
followed by transferring holes generated in the valence band of irradiated FT to
HRP. The excited HRP oxidized substrates (amplex ultrared: AUR) accompanied by
two-electron reduction to regenerate the resting state. In addition, the
catalytic activity was clearly switched by turning on and off the light source.
PMID- 26439704
TI - The Relationship Between Development of Neuronal and Astrocytic Tau Pathologies
in Subcortical Nuclei and Progression of Argyrophilic Grain Disease.
AB - Progressive supranuclear palsy (PSP) cases frequently have argyrophilic grain
disease (AGD). However, the PSP-like tau pathology in AGD cases has not been
fully clarified. To address this, we examined tau pathologies in the subcortical
nuclei and frontal cortex in 19 AGD cases that did not meet the pathological
criteria of PSP or corticobasal degeneration, nine PSP cases and 20 Braak NFT
stage-matched controls. Of the 19 AGD cases, five (26.3%) had a few Gallyas
positive tau-positive tufted astrocytes (TAs) and Gallyas-negative tau-positive
TA-like astrocytic inclusions (TAIs), and six (31.6%) had only TAIs in the
striatum and/or frontal cortex. Subcortical tau pathology was sequentially and
significantly greater in AGD cases lacking these tau-positive astrocytic lesions,
AGD cases having them, and PSP cases than in controls. There was a significant
correlation between three histologic factors, including the AGD stage and the
quantities of subcortical neuronal and astrocytic tau pathologies. Tau
immunoblotting demonstrated 68- and 64-kDa bands and 33-kDa low-molecular mass
tau fragments in PSP cases, and although with lesser intensity, in AGD cases with
and without TAs and TAIs also. Given these findings, the progression of AGD may
be associated with development of the neuronal and astrocytic tau pathologies
characteristic of PSP.
PMID- 26439706
TI - Amorphous and Crystalline Sodium Tantalate Composites for Photocatalytic Water
Splitting.
AB - A facile hydrothermal synthesis protocol for the fabrication of sodium tantalates
for photocatalytic water splitting is presented. Mixtures of tantalum and sodium
ethoxide precursors were dispersed in ethanol, and ammonium hydroxide solution
was used as mineralizer. By adjusting the amount of mineralizer, a variety of
sodium tantalates with various morphologies, textural parameters, band gaps,
crystal phases, and degrees of crystallinity were fabricated. The reaction was
carefully monitored with a pressure sensor inside the autoclave reactor, and the
obtained samples were characterized using X-ray diffraction, transmission
electron microscopy, N2-physisorption, and ultraviolet-visible light
spectroscopy. Among the series, the amorphous sample and the composite sample
that consists of amorphous and crystalline phases showed superior activity toward
photocatalytic hydrogen production than highly crystalline samples. Particularly,
an amorphous sodium tantalate with a small fraction of crystalline nanoparticles
with perovskite structure was found to be the most active sample, reaching a
hydrogen rate of 3.6 mmol h(-1) from water/methanol without the use of any
cocatalyst. Despite its amorphous nature, this photocatalyst gave an apparent
photocatalyst activity of 1200 MUmol g(-1) L(-1) h(-1) W(1-), which is 4.5-fold
higher than highly crystalline NaTaO3. In addition, the most active sample gave
promising activity for overall water splitting with a hydrogen production rate of
94 MUmol h(-1), which is superior to highly crystalline NaTaO3 prepared by
conventional solid-solid state route.
PMID- 26439705
TI - Effect of Age on Working Memory Performance and Cerebral Activation after Mild
Traumatic Brain Injury: A Functional MR Imaging Study.
AB - PURPOSE: To evaluate the age effect on working memory (WM) performance and
functional activation after mild traumatic brain injury (MTBI). MATERIALS AND
METHODS: This study was approved by the local research ethics committee. All
participants provided written informed consent. N-back WM cerebral activation was
assessed with functional magnetic resonance (MR) imaging in 13 younger (mean age,
26.2 years +/- 2.9; range, 21-30 years) and 13 older (mean age, 57.8 years +/-
6.6; range, 51-68 years) patients with MTBI and 26 age- and sex-matched control
subjects. Two functional MR images were obtained within 1 month after injury and
6 weeks after the initial study. Group comparison and regression analysis were
performed among postconcussion symptoms, neuropsychologic tests, and WM activity
in both groups. RESULTS: In younger patients, initial hyperactivation was seen in
the right precuneus and right inferior parietal gyrus (P = .047 and P = .025,
respectively) in two-back greater than one-back conditions compared with younger
control subjects, whereas in older patients, hypoactivation was seen in the right
precuneus and right inferior frontal gyrus (P = .013 and P =.019, respectively)
compared with older control subjects. Increased WM activity was associated with
increased postconcussion symptoms in the right precuneus (r = 0.57; P = .026) and
right inferior frontal gyrus (r = 0.60; P = .019) and poor WM performance in the
right precuneus (r = -0.55; P = .027) in younger patients at initial studies but
not in older patients. At follow-up examinations, partial recovery of activation
pattern and decreased postconcussion symptoms (P = .04) were observed in younger
patients but not in older patients. CONCLUSION: The different manifestations of
postconcussion symptoms at functional MR imaging between younger and older
patients confirmed the important role of age in the activation, modulation, and
allocation of WM processing resources after MTBI. These findings also supported
that younger patients have better neural plasticity and clinical recovery than do
older patients.
PMID- 26439702
TI - Molecular signature of pancreatic adenocarcinoma: an insight from genotype to
phenotype and challenges for targeted therapy.
AB - INTRODUCTION: Pancreatic adenocarcinoma remains one of the most clinically
challenging cancers despite an in-depth characterization of the molecular
underpinnings and biology of this disease. Recent whole-genome-wide studies have
elucidated the diverse and complex genetic alterations which generate a unique
oncogenic signature for an individual pancreatic cancer patient and which may
explain diverse disease behavior in a clinical setting. AREAS COVERED: In this
review article, we discuss the key oncogenic pathways of pancreatic cancer
including RAS-MAPK, PI3KCA and TGF-beta signaling, as well as the impact of these
pathways on the disease behavior and their potential targetability. The role of
tumor suppressors particularly BRCA1 and BRCA2 genes and their role in pancreatic
cancer treatment are elaborated upon. We further review recent genomic studies
and their impact on future pancreatic cancer treatment. EXPERT OPINION: Targeted
therapies inhibiting pro-survival pathways have limited impact on pancreatic
cancer outcomes. Activation of pro-apoptotic pathways along with suppression of
cancer-stem-related pathways may reverse treatment resistance in pancreatic
cancer. While targeted therapy or a 'precision medicine' approach in pancreatic
adenocarcinoma remains an elusive challenge for the majority of patients, there
is a real sense of optimism that the strides made in understanding the molecular
underpinnings of this disease will translate into improved outcomes.
PMID- 26439707
TI - Host Phenology and Leaf Effects on Susceptibility of California Bay Laurel to
Phytophthora ramorum.
AB - Spread of the plant pathogen Phytophthora ramorum, causal agent of the forest
disease sudden oak death, is driven by a few competent hosts that support spore
production from foliar lesions. The relationship between traits of a principal
foliar host, California bay laurel (Umbellularia californica), and susceptibility
to P. ramorum infection were investigated with multiple P. ramorum isolates and
leaves collected from multiple trees in leaf-droplet assays. We examined whether
susceptibility varies with season, leaf age, or inoculum position. Bay laurel
susceptibility was highest during spring and summer and lowest in winter. Older
leaves (>1 year) were more susceptible than younger ones (8 to 11 months).
Susceptibility was greater at leaf tips and edges than the middle of the leaf.
Leaf surfaces wiped with 70% ethanol were more susceptible to P. ramorum
infection than untreated leaf surfaces. Our results indicate that seasonal
changes in susceptibility of U. californica significantly influence P. ramorum
infection levels. Thus, in addition to environmental variables such as
temperature and moisture, variability in host plant susceptibility contributes to
disease establishment of P. ramorum.
PMID- 26439709
TI - A Hybrid Program for Fitting Rotationally Resolved Spectra of Floppy Molecules
with One Large-Amplitude Rotatory Motion and One Large-Amplitude Oscillatory
Motion.
AB - A new hybrid-model fitting program for methylamine-like molecules has been
developed, on the basis of an effective Hamiltonian in which the ammonia-like
inversion motion is treated using a tunneling formalism, whereas the internal
rotation motion is treated using an explicit kinetic energy operator and
potential energy function. The Hamiltonian in the computer program is set up as a
2 * 2 partitioned matrix, where each diagonal block contains a traditional
torsion-rotation Hamiltonian (as in the earlier program BELGI), and the two off
diagonal blocks contain tunneling terms. This hybrid formulation permits the use
of the permutation-inversion group G6 (isomorphic to C(3v)) for terms in the two
diagonal blocks but requires G12 for terms in the off-diagonal blocks. The first
application of the new program is to 2-methylmalonaldehyde. Microwave data for
this molecule were previously fit using an all-tunneling Hamiltonian formalism to
treat both large-amplitude motions. For 2-methylmalonaldehyde, the hybrid program
achieves the same quality of fit as was obtained with the all-tunneling program,
but fits with the hybrid program eliminate a large discrepancy between internal
rotation barriers in the OH and OD isotopologs of 2-methylmalonaldehyde that
arose in fits with the all-tunneling program. This large isotopic shift in
internal rotation barrier is thus almost certainly an artifact of the all
tunneling model. Other molecules for application of the hybrid program are
mentioned.
PMID- 26439710
TI - Versatile Multicomponent Reaction Macrocycle Synthesis Using alpha-Isocyano-omega
carboxylic Acids.
AB - The direct macrocycle synthesis of alpha-isocyano-omega-carboxylic acids via an
Ugi multicomponent reaction is introduced. This multicomponent reaction (MCR)
protocol differs by being especially short, convergent, and versatile, giving
access to 12-22 membered rings.
PMID- 26439708
TI - Contaminated water delivery as a simple and effective method of experimental
Salmonella infection.
AB - AIM: In most infectious disease models, it is assumed that gavage needle
infection is the most reliable means of pathogen delivery to the GI tract.
However, this methodology can cause esophageal tearing and induces stress in
experimental animals, both of which have the potential to impact early infection
and the subsequent immune response. MATERIALS & METHODS: C57BL/6 mice were orally
infected with virulent Salmonella Typhimurium SL1344 either by intragastric
gavage preceded by sodium bicarbonate, or by contamination of drinking water.
RESULTS: We demonstrate that water contamination delivery of Salmonella is
equivalent to gavage inoculation in providing a consistent model of infection.
Furthermore, exposure of mice to contaminated drinking water for as little as 4 h
allowed maximal mucosal and systemic infection, suggesting an abbreviated window
exists for natural intestinal entry. CONCLUSION: Together, these data question
the need for gavage delivery for infection with oral pathogens.
PMID- 26439712
TI - Trends in Anemia Management in Hemodialysis Patients with Cancer.
AB - BACKGROUND: Erythropoiesis-stimulating agents (ESAs), intravenous iron, and blood
transfusion are used to treat anemia in both end-stage renal disease (ESRD) and
cancer. However, anemia treatment patterns have not been described among ESRD
patients undergoing hemodialysis with concurrent cancer, especially in the recent
era of ESA-related safety concerns. METHODS: We analyzed Medicare data from a
cohort of hemodialysis patients diagnosed with incident cancer. We used
multivariable generalized linear models to estimate trends and patterns in ESA
use, iron use, transfusion use, epoetin alfa (EPO) dose, iron dose, and resulting
hemoglobin levels (2000-2011). RESULTS: Of 43,760 eligible patients, quarterly
ESA use declined slightly from a peak of 94.1 to 90.0%. Quarterly EPO dose
increased from 2000 to 2004, then declined; quarterly hemoglobin levels followed
a similar pattern. Iron use increased rapidly from 46.9 to 79.3%. Iron dose
increased until 2010 and then declined. There was an increase in the quarterly
transfusion use (6.3-11.7%) and in the mean number of transfusion days per year
(1.4-1.8). Anemia treatment patterns varied by demographic/clinical subgroups,
especially among patients receiving chemotherapy, who required higher ESA use,
EPO dose, and frequency of transfusions. CONCLUSIONS: Despite safety concerns
about ESAs in both the ESRD and cancer populations, the proportion of
hemodialysis patients with cancer who used ESAs between 2000 and 2011 remained
extremely high. EPO dose and hemoglobin levels increased and then decreased. Iron
use, iron dose, and transfusions increased substantially. Future research
examining the risk-benefit profile of different anemia management strategies in
the dialysis population with cancer is needed.
PMID- 26439713
TI - Alternative Splicing Signatures in RNA-seq Data: Percent Spliced in (PSI).
AB - Thousands of alternative exons are spliced out of messenger RNA to increase
protein diversity. High-throughput sequencing of short cDNA fragments (RNA-seq)
generates a genome-wide snapshot of these post-transcriptional processes. RNA-seq
reads yield insights into the regulation of alternative splicing by revealing the
usage of known or unknown splice sites as well as the expression level of exons.
Constitutive exons are never covered by split alignments, whereas alternative
exonic parts are located within highly expressed splicing junctions. The ratio
between reads including or excluding exons, also known as percent spliced in
index (PSI), indicates how efficiently sequences of interest are spliced into
transcripts. This protocol describes a method to calculate the PSI without prior
knowledge of splicing patterns. It provides a quantitative, global assessment of
exon usage that can be integrated with other tools that identify differential
isoform processing. Novel, complex splicing events along a genetic locus can be
visualized in an exon-centric manner and compared across conditions.
PMID- 26439714
TI - Practical Integration-Free Episomal Methods for Generating Human Induced
Pluripotent Stem Cells.
AB - The advent of induced pluripotent stem (iPS) cell technology has revolutionized
biomedicine and basic research by yielding cells with embryonic stem (ES) cell
like properties. The use of iPS-derived cells for cell-based therapies and
modeling of human disease holds great potential. While the initial description of
iPS cells involved overexpression of four transcription factors via viral vectors
that integrated within genomic DNA, advances in recent years by our group and
others have led to safer and higher quality iPS cells with greater efficiency.
Here, we describe commonly practiced methods for non-integrating induced
pluripotent stem cell generation using nucleofection of episomal reprogramming
plasmids. These methods are adapted from recent studies that demonstrate
increased hiPS cell reprogramming efficacy with the application of three powerful
episomal hiPS cell reprogramming factor vectors and the inclusion of an accessory
vector expressing EBNA1.
PMID- 26439715
TI - Chemically Defined Culture and Cardiomyocyte Differentiation of Human Pluripotent
Stem Cells.
AB - Since the first discovery that human pluripotent stem cells (hPS cells) can
differentiate to cardiomyocytes, efforts have been made to optimize the
conditions under which this process occurs. One of the most effective
methodologies to optimize this process is reductionist simplification of the
medium formula, which eliminates complex animal-derived components to help reveal
the precise underlying mechanisms. Here we describe our latest, cost-effective
and efficient methodology for the culture of hPS cells in the pluripotent state
using a modified variant of chemically defined E8 medium. We provide exact
guidelines for cell handling under these conditions, including non-enzymatic EDTA
passaging, which have been optimized for subsequent cardiomyocyte
differentiation. We describe in depth the latest version of our monolayer
chemically defined small molecule differentiation protocol, including metabolic
selection-based cardiomyocyte purification and the addition of triiodothyronine
to enhance cardiomyocyte maturation. Finally, we describe a method for the
dissociation of hPS cell-derived cardiomyocytes, cryopreservation, and thawing.
PMID- 26439716
TI - Interpreting de novo Variation in Human Disease Using denovolyzeR.
AB - Spontaneously arising (de novo) genetic variants are important in human disease,
yet every individual carries many such variants, with a median of 1 de novo
variant affecting the protein-coding portion of the genome. A recently described
mutational model provides a powerful framework for the robust statistical
evaluation of such coding variants, enabling the interpretation of de novo
variation in human disease. Here we describe a new open-source software package,
denovolyzeR, that implements this model and provides tools for the analysis of de
novo coding sequence variants.
PMID- 26439717
TI - Management of Incidental Findings in Clinical Genomic Sequencing.
AB - Genomic sequencing is becoming accurate, fast, and increasingly inexpensive, and
is rapidly being incorporated into clinical practice. Incidental or secondary
findings, which can occur in large numbers from genomic sequencing, are a
potential barrier to the utility of this new technology due to their relatively
high prevalence and the lack of evidence or guidelines available to guide their
clinical interpretation. This unit reviews the definition, classification, and
management of incidental findings from genomic sequencing. The unit focuses on
the clinical aspects of handling incidental findings, with an emphasis on the key
role of clinical context in defining incidental findings and determining their
clinical relevance and utility.
PMID- 26439718
TI - Huntington Disease: Molecular Diagnostics Approach.
AB - Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in
the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington
disease for diagnostic confirmation and disease prediction requires detection of
the CAG repeat expansion. There are three main types of HD genetic testing: (1)
diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to
determine whether an at-risk individual inherited the expanded allele, and (3)
prenatal testing to determine whether the fetus has inherited the expanded
allele. This unit includes protocols that describe the complementary use of
polymerase chain reactions (PCR) and Southern blot hybridization to accurately
measure the CAG trinucleotide repeat size and interpret the test results. In
addition, an indirect linkage analysis that does not reveal the unwanted parental
HD status in a prenatal testing will also be discussed.
PMID- 26439719
TI - Essential oil of Zygophyllum album inhibits key-digestive enzymes related to
diabetes and hypertension and attenuates symptoms of diarrhea in alloxan-induced
diabetic rats.
AB - CONTEXT: Zygophyllum album L. (Zygophyllaceae), commonly known as Bougriba, is
widely used to treat diabetes, digestive tract spasm, and hypertension in folk
medicine, in Tunisia. OBJECTIVE: This study investigates the antidiabetic,
antidiarrheal, and antihypertensive activities of the leaves of the essential oil
from Zygophyllum album (OZA) in alloxan-induced diabetic rats. MATERIALS AND
METHODS: The oil was obtained by hydrodistillation and analyzed by GC-MS. Males
rats were divided into four groups: control, diabetic-untreated group, diabetic
treated group with acarbose (10 mg/kg), and diabetic-treated rats with OZA (200
mg/kg) for 30 d. RESULTS: At the end of the experimental period, the OZA
significantly decreased the activity of alpha-amylase in pancreas and serum of
the diabetic rats by 43% and 38%, respectively, which led to reduce the serum
glucose level by 60% and lower of glycated hemoglobin (HbA1c) rate by 17% as
compared with untreated diabetic animals. Moreover, the OZA treatment attenuated
symptoms of diarrhea, improved lipid disorders, and hypertension through
inhibiting the pancreatic lipase and angiotensin-converting enzyme (ACE)
activities by 47% and 25%, respectively, in serum of diabetic rats. CONCLUSION:
OZA showed a good effect in the management of diabetes mellitus and exerted
preventive action from related hypertension.
PMID- 26439720
TI - Exploring Risk and Protective Factors for Recent and Past Intimate Partner
Violence Against New Zealand Women.
AB - The purpose of this investigation was to identify risk and protective factors
associated with intimate partner violence (IPV) in a high-income country (New
Zealand) and to identify those factors that distinguish between current versus
previous exposure to IPV. Data were drawn from the New Zealand replication of the
World Health Organization's Multi-Country Study on Women's Health and Domestic
Violence. Logistic regression was conducted to identify those variables
associated with experience of IPV. Problem drinking, a partner who has concurrent
sexual relationships, and a partner who is violent outside the home were
associated with increased likelihood of current as opposed to previous experience
of IPV. Increased household income and both the respondent and her partner being
employed were associated with reduced likelihood that women would experience
current as opposed to prior IPV. The findings point toward the need for
comprehensive approaches to reduce all forms of violence and to contribute to the
primary prevention of IPV. Strategies that address early exposure to violence,
problematic alcohol consumption, gender transformative approaches to working with
boys and men, and economic empowerment for women may all hold promise.
PMID- 26439721
TI - Impact of Growth Hormone on Adult Bone Quality in Turner Syndrome: A HR-pQCT
Study.
AB - Women with Turner syndrome (TS) are known to be at risk of osteoporosis. While
childhood growth hormone (GH) treatment is common in TS, the impact of this
therapy on bone health has been poorly understood. The objective of this study
was to determine the influence of childhood GH treatment on adult bone quality in
women with TS. 28 women aged 17-45 with confirmed TS (12 GH-treated) agreed to
participate in this cross-sectional study. Dual X-ray absorptiometry (DXA) of
lumbar spine, hip, and radius and high-resolution peripheral quantitative
computed tomography (HR-pQCT) scans of the radius and tibia were used to
determine standard morphological and micro-architectural parameters of bone
health. Finite element (FE) analysis and polar moment of inertia (pMOI) were used
to estimate bone strength. GH-treated subjects were +7.4 cm taller (95% CI 2.5
12.3 cm, p = 0.005). DXA-determined areal BMD of hip, spine, and radius was
similar between treatment groups. Both tibial and radial total bone areas were
greater among GH-treated subjects (+20.4 and +21.2% respectively, p < 0.05),
while other micro-architectural results were not different between groups. pMOI
was significantly greater among GH-treated subjects (radius +35.0%, tibia +34.0%,
p < 0.05). Childhood GH treatment compared to no treatment in TS was associated
with an increased height, larger bones, and greater pMOI, while no significant
difference in DXA-derived BMD, HR-pQCT micro-architectural parameters, or FE
estimated bone strength was detected. The higher pMOI and greater bone size may
confer benefit for fracture reduction in these GH-treated patients.
PMID- 26439722
TI - Impact of preloading either dairy or soy milk on postprandial glycemia,
insulinemia and gastric emptying in healthy adults.
AB - PURPOSE: Milk protein ingestion reduces post-meal glycemia when consumed either
before or together with carbohydrate foods. The aim of this study was to compare
the effects of dairy and soy milk consumed either before (preload) or together
with (co-ingestion) a carbohydrate (bread), on postprandial blood glucose,
insulin and gastric emptying in healthy participants. METHODS: Twelve healthy
Chinese male participants were studied on five separate occasions using a
randomized crossover design. White wheat bread consumed with water was used as a
reference meal. Capillary and venous bloods were sampled pretest and 3.5 h post
test meal for glucose and insulin measurement. Gastric emptying was measured
using real-time ultrasonography. RESULTS: Co-ingestion of dairy milk or soy milk
with bread lowered postprandial blood glucose response and glycemic index. Co
ingesting soy milk with bread increased insulin response and insulinemic index
significantly compared to co-ingestion of dairy milk and preload treatments.
Preloads (30 min prior to bread) significantly lowered postprandial glycemia and
insulinemia compared to co-ingestion. Gastric emptying was slower after co
ingesting dairy milk with bread than after reference meal. CONCLUSIONS:
Preloading either soy milk or dairy milk results in greater reduction in glycemic
response compared to co-ingestion alone. This dietary practice may have
therapeutic advantage in communities consuming high GI diets. Optimal glucose
control may have the potential for increasing the time of transition from
prediabetes to type 2 diabetes in Asian communities. CLINICAL TRIAL REGISTRATION:
This trial was registered at clinicaltrials.gov as NCT 02151188.
PMID- 26439724
TI - Breakdown of Bragg-Gray behaviour for low-density detectors under electronic
disequilibrium conditions in small megavoltage photon fields.
AB - In small photon fields ionisation chambers can exhibit large deviations from
Bragg-Gray behaviour; the EGSnrc Monte Carlo (MC) code system has been employed
to investigate this 'Bragg-Gray breakdown'. The total electron (+positron)
fluence in small water and air cavities in a water phantom has been computed for
a full linac beam model as well as for a point source spectrum for 6 MV and 15 MV
qualities for field sizes from 0.25 * 0.25 cm(2) to 10 * 10 cm(2). A water-to
air perturbation factor has been derived as the ratio of total electron
(+positron) fluence, integrated over all energies, in a tiny water volume to that
in a 'PinPoint 3D-chamber-like' air cavity; for the 0.25 * 0.25 cm(2) field
size the perturbation factors are 1.323 and 2.139 for 6 MV and 15 MV full linac
geometries respectively. For the 15 MV full linac geometry for field sizes of 1
* 1 cm(2) and smaller not only the absolute magnitude but also the 'shape' of
the total electron fluence spectrum in the air cavity is significantly different
to that in the water 'cavity'. The physics of this 'Bragg-Gray breakdown' is
fully explained, making reference to the Fano theorem. For the 15 MV full linac
geometry in the 0.25 * 0.25 cm(2) field the directly computed MC dose ratio,
water-to-air, differs by 5% from the product of the Spencer-Attix stopping-power
ratio (SPR) and the perturbation factor; this 'difference' is explained by the
difference in the shapes of the fluence spectra and is also formulated
theoretically. We show that the dimensions of an air-cavity with a perturbation
factor within 5% of unity would have to be impractically small in these highly
non-equilibrium photon fields. In contrast the dose to water in a 0.25 * 0.25
cm(2) field derived by multiplying the dose in the single-crystal diamond
dosimeter (SCDDo) by the Spencer-Attix ratio is within 2.9% of the dose computed
directly in the water voxel for full linac geometry at both 6 and 15 MV, thereby
demonstrating that this detector exhibits quasi Bragg-Gray behaviour over a wide
range of field sizes and beam qualities.
PMID- 26439723
TI - Gastrointestinal stability of urolithins: an in vitro approach.
AB - PURPOSE: Urolithins are bioactive ellagitannin-derived metabolites showing a wide
phenotypic variation in their production by the gut microbiota. This work
represents a first in vitro step toward the development of new strategies focused
on the oral supplementation of urolithins with the aim of overcoming their
selective production and making their putative health benefits available for the
whole population. METHODS: In order to study their gastrointestinal stability,
urolithin A, urolithin B, and urolithin B-glucuronide, as well as ellagic acid,
were subjected to a simulated gastrointestinal digestion model consisting of
oral, gastric, and pancreatic steps followed by a 24-h fecal fermentation. The
effect of the entero-hepatic recirculation on urolithin B-glucuronide, a phase II
metabolite, was also investigated. RESULTS: Urolithin B was the molecule able to
resist to a greater extent the conditions of the gastrointestinal tract, while
urolithin A and ellagic acid were drastically unstable during the colonic step.
Conjugation with glucuronic acid, ideally occurring in the liver, conferred to
urolithin B an increased stability, which may be interesting in the framework of
entero-hepatic recirculation. CONCLUSION: This set of experiments lets
hypothesize that orally supplemented urolithins may come into contact with the
colonic epithelium and become accessible for uptake or exert local anti
inflammatory activity, overcoming the limitations of enterotypes unable to
convert ellagitannins into these putatively beneficial metabolites.
PMID- 26439727
TI - VA Palliative Care: The Filling and Relaxing of Diastole.
PMID- 26439725
TI - Quantitative analysis of nuclear shape in oral squamous cell carcinoma is useful
for predicting the chemotherapeutic response.
AB - The number of people afflicted with oral carcinoma in Japan has increased in
recent years. Although preoperative neoadjuvant therapy with cisplatin and 5
fluorouracil are performed, chemotherapeutic response varies widely among the
patients. With the aim of establishing novel indices to predict the therapeutic
response to chemotherapy, we investigated the relationship between morphological
features of pre-treatment oral carcinoma nuclei and the chemotherapeutic response
using quantifying morphology of cell nuclei in pathological specimen images. We
measured 4 morphological features of the nucleus of oral squamous cell carcinoma
cases classified by the response to chemotherapy: No Change (NC) group, Partial
Response (PR) group and Complete Response (CR) group. Furthermore, we performed
immunohistochemical staining for p53 and Ki67 and calculated their positive rates
in cancer tissues. Compactness and symmetry of the nucleus were significantly
higher and nuclear edge response was significantly lower in cancer cells with
lower chemotherapeutic responses compared high chemotherapeutic responders. As
for positive rates of p53 and Ki67, there were no significant differences between
any of the response groups. Morphological features of cancer cell nuclei in
pathological specimens are sensitive predictive factors for the chemotherapeutic
response to oral squamous cell carcinoma.
PMID- 26439728
TI - Opioid-Induced Constipation Part 2: Newer Therapies #295.
PMID- 26439729
TI - Camera-based single-molecule FRET detection with improved time resolution.
AB - The achievable time resolution of camera-based single-molecule detection is often
limited by the frame rate of the camera. Especially in experiments utilizing
single-molecule Forster resonance energy transfer (smFRET) to probe
conformational dynamics of biomolecules, increasing the frame rate by either
pixel-binning or cropping the field of view decreases the number of molecules
that can be monitored simultaneously. Here, we present a generalised excitation
scheme termed stroboscopic alternating-laser excitation (sALEX) that
significantly improves the time resolution without sacrificing highly
parallelised detection in total internal reflection fluorescence (TIRF)
microscopy. In addition, we adapt a technique known from diffusion-based confocal
microscopy to analyse the complex shape of FRET efficiency histograms. We apply
both sALEX and dynamic probability distribution analysis (dPDA) to resolve
conformational dynamics of interconverting DNA hairpins in the millisecond time
range.
PMID- 26439730
TI - A multitude of variations in the configuration of the circle of Willis: an
autopsy study.
AB - The circle of Willis (CW) is an anastomotic system of arteries located at the
base of the brain. The aim of the study was to evaluate the anatomic
configuration of the CW in the Polish population and to compare results with
previously conducted research. Brains were obtained from 100 recently deceased
human adults, and the diameters of cerebral vessels were measured using a slide
caliper. Cerebral vessels were observed, paying attention to their origin,
diameter, typical configuration and variations. Twenty-seven percent of cases
presented the typical literature pattern. The remaining 73 % of all cases were
atypical; in 16 % the CW was incomplete and in 57 % complete. Atypical findings
involved the posterior communicating artery (PcomA), 62 %; anterior communicating
artery (AcomA), 22 %; anterior cerebral artery (ACA), 14 %; posterior cerebral
artery (PCA), 8 %. The most common variations were bilateral hypoplastic PcomAs
(27 % of cases) and unilateral hypoplastic PcomAs (19 % of cases). Only 9 of the
22 types of CW variations classified previously in the literature were observed,
and 26 variations (36 cases) in our study were labeled as 'other' type. Mean
diameter values for typical CW patterns were internal carotid artery = 3.6 mm,
ACA = 2.3 mm, AcomA = 1.9 mm, PCA = 2.2 mm and PcomA = 1.4 mm. Circle of Willis
variations have a large impact on clinical practice. This study shows many rare
variations that should be taken into consideration to avoid any unexpected
complications during surgical procedures involving cerebral vessels.
PMID- 26439731
TI - Molecular and anatomical evidence for the input pathway- and target cell type
dependent regulation of glutamatergic synapses.
AB - Glutamate mediates most fast excitatory transmission in the central nervous
system by activating primarily two types of ionotropic glutamate receptors: alpha
amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D
aspartate (NMDA) receptors. Differential subunit combinations generate great
functional diversity in both categories of receptors, making them highly suitable
for meeting complex functional requirements. Converging evidence has indicated
that distinct AMPA and NMDA receptor subtypes are selectively targeted to
functionally different synapses according to different factors, including
presynaptic inputs, postsynaptic cell types, and synaptic configurations. This
article provides an overview of recent progress in understanding the basic
principles governing the synaptic allocation of AMPA and NMDA receptors, and
discusses the underlying mechanisms and functional implications.
PMID- 26439732
TI - Anomalous course of the external carotid artery.
AB - The course and the branching patterns of the external carotid artery were
investigated macroscopically in a total of 550 bodies or 1100 head sides of
Japanese subjects, donated for student dissection at Kumamoto University from
1994 to 2014. With the exception of 14 head sides, the external carotid arteries
running between the posterior belly of the digastric and stylohyoid muscles were
found in 42 (3.87 %) out of 1086 head sides. Strictly speaking, they passed
between the stylohyoid muscle and the stylohyoid branch of the facial nerve in 23
out of these 42 head sides. In the remaining 19 instances, the stylohyoid branch
of the facial nerve was cut and its relationship to the external carotid artery
was not clear. The external carotid artery running lateral to the intact
stylohyoid branch of the facial nerve, medial to the digastric muscle was not
found. The external carotid arteries running lateral to the digastric muscle were
found in 4 (0.37 %) out of 1086 head sides. As a result, it is proposed that
plural, potential courses of the external carotid artery originally exist and
that some parts of such potential courses remain as branches of the external
carotid artery in the usual instance, while the anomalous courses of the external
carotid artery are induced mainly by anastomosis between the muscular branches
supplying the wall of the head and neck in contrast to the usual external carotid
artery induced mainly by the branches originally supplying the pharynx.
PMID- 26439733
TI - Sleeve Gastrectomy Decreases Body Weight, Whole-Body Adiposity, and Blood
Pressure Even in Aged Diet-Induced Obese Rats.
AB - BACKGROUND: Aging and obesity are two conditions associated with increased risk
of cardiovascular disease. Our aim was to analyze whether an advanced age affects
the beneficial effects of sleeve gastrectomy on weight loss and blood pressure in
an experimental model of diet-induced obesity (DIO). METHODS: Young (6-month-old)
and old (18-month-old) male Wistar DIO rats (n = 101) were subjected to surgical
(sham operation and sleeve gastrectomy) or dietary interventions (pair-fed to the
amount of food eaten by sleeve gastrectomized animals). Systolic (SBP), diastolic
(DBP), and mean (MBP) blood pressure values and heart rate (HR) were recorded in
conscious, resting animals by non-invasive tail-cuff plethysmography before and 4
weeks after surgical or dietary interventions. RESULTS: Aging was associated with
higher (P < 0.05) body weight and subcutaneous and perirenal fat mass as well as
mild cardiac hypertrophy. Sleeve gastrectomy induced a reduction in body weight,
whole-body adiposity, and serum total ghrelin in both young and old DIO rats. The
younger group achieved a higher excess weight loss than the older group (164 +/-
60 vs. 82 +/- 17 %, P < 0.05). A significant (P < 0.05) decrease in insulin
resistance, SBP, DBP, MBP, and HR without changes in heart weight was observed
after sleeve gastrectomy independently of age. CONCLUSION: Our results provide
evidence for the effectiveness of sleeve gastrectomy without increased operative
risk in body weight and blood pressure reduction even in aged animals via
endocrine changes that go beyond the mere caloric restriction.
PMID- 26439736
TI - Racial and geographic disparities in the patterns of care and costs at the end of
life for patients with lung cancer in 2007-2010 after the 2006 introduction of
bevacizumab.
AB - OBJECTIVES: To examine racial/ethnic and geographical disparities in cancer care
and costs during the last 6 months of life for lung cancer decedents after the
Food and Drug Administration's approval of expensive bevacizumab in October 2006.
METHODS: We identified 37,393 cases from the Surveillance, Epidemiology and End
Results (SEER) cancer registries and Medicare linked databases who were diagnosed
with non-small cell lung cancer of all stages in 1991-2009 and died between July
2007 and December 2010. RESULTS: Overall, the proportion of patients receiving
chemotherapy/targeted therapy (31.0%), bevacizumab (4.6%), growth factors
(16.0%), surgery (2.8%), and hospice care (60.9) in the last 6 months of life was
higher in whites than in other ethnic populations. Hospitalization rate was
higher in blacks (83.2%) than in whites (76.0%) and others (78.0%). Those from
metro areas had slightly higher percentages of receiving chemotherapy/targeted
therapy, bevacizumab, growth factors, and hospice care, but had a higher
hospitalization rate and lower emergency care visit. Mean total health care cost
was $42,749 for the last 6 months of life in patients with lung cancer. Adjusted
mean health care cost in the last 6 months of life was significantly higher in
blacks or other ethnic population as compared to whites. CONCLUSION: There were
substantial racial/ethnic and geographic disparities in the types of cancer care
and costs in the last 6 months of life among lung cancer decedents, regardless of
the length of survival times and hospice care status. A clinical guideline may
help the appropriate use of costly treatment modalities and minimize
racial/geographic disparities.
PMID- 26439737
TI - Use of a Referring Physician Survey to Direct and Evaluate Department-Wide
Radiology Quality Improvement Efforts.
PMID- 26439734
TI - Kinetic characterization of trans-proteolytic activity of Chikungunya virus
capsid protease and development of a FRET-based HTS assay.
AB - Chikungunya virus (CHIKV) capsid protein (CVCP) is a serine protease that
possesses cis-proteolytic activity essential for the structural polyprotein
processing and plays a key role in the virus life cycle. CHIKV being an emerging
arthropod-borne pathogenic virus, is a public health concern worldwide. No
vaccines or specific antiviral treatment is currently available for chikungunya
disease. Thus, it is important to develop inhibitors against CHIKV enzymes to
block key steps in viral reproduction. In view of this, CVCP was produced
recombinantly and purified to homogeneity. A fluorescence resonance energy
transfer (FRET)-based proteolytic assay was developed for high throughput
screening (HTS). A FRET peptide substrate (DABCYL-GAEEWSLAIE-EDANS) derived from
the cleavage site present in the structural polyprotein of CVCP was used. The
assay with a Z' factor of 0.64 and coefficient of variation (CV) is 8.68% can be
adapted to high throughput format for automated screening of chemical libraries
to identify CVCP specific protease inhibitors. Kinetic parameters Km and kcat/Km
estimated using FRET assay were 1.26 +/- 0.34 MUM and 1.11 * 10(3) M(-1) sec(-1)
respectively. The availability of active recombinant CVCP and cost effective
fluorogenic peptide based in vitro FRET assay may serve as the basis for
therapeutics development against CHIKV.
PMID- 26439735
TI - KIF7 Controls the Proliferation of Cells of the Respiratory Airway through
Distinct Microtubule Dependent Mechanisms.
AB - The cell cycle must be tightly coordinated for proper control of embryonic
development and for the long-term maintenance of organs such as the lung. There
is emerging evidence that Kinesin family member 7 (Kif7) promotes Hedgehog (Hh)
signaling during embryonic development, and its misregulation contributes to
diseases such as ciliopathies and cancer. Kif7 encodes a microtubule interacting
protein that controls Hh signaling through regulation of microtubule dynamics
within the primary cilium. However, whether Kif7 has a function in nonciliated
cells remains largely unknown. The role Kif7 plays in basic cell biological
processes like cell proliferation or cell cycle progression also remains to be
elucidated. Here, we show that Kif7 is required for coordination of the cell
cycle, and inactivation of this gene leads to increased cell proliferation in
vivo and in vitro. Immunostaining and transmission electron microscopy
experiments show that Kif7dda/dda mutant lungs are hyperproliferative and exhibit
reduced alveolar epithelial cell differentiation. KIF7 depleted C3H10T1/2
fibroblasts and Kif7dda/dda mutant mouse embryonic fibroblasts have increased
growth rates at high cellular densities, suggesting that Kif7 may function as a
general regulator of cellular proliferation. We ascertained that in G1, Kif7 and
microtubule dynamics regulate the expression and activity of several components
of the cell cycle machinery known to control entry into S phase. Our data suggest
that Kif7 may function to regulate the maintenance of the respiratory airway
architecture by controlling cellular density, cell proliferation, and cycle exit
through its role as a microtubule associated protein.
PMID- 26439738
TI - Radiology Residency Spots Should Be Drastically and Immediately Reduced.
PMID- 26439739
TI - Rapid Proliferation and Differentiation of a Subset of Circulating IgM Memory B
Cells to a CpG/Cytokine Stimulus In Vitro.
AB - Circulating human IgM expressing memory B cells have been incompletely
characterized. Here, we compared the phenotype and in vitro functional response
(capacity to proliferate and differentiate to antibody secreting cells) in
response to CpG and a cytokine cocktail (IL-2, IL-6, and IL-10) of sorted naive B
cells, IgM memory B cells and isotype-switched circulating memory B cells.
Compared to naive B cells, IgM memory B cells had lower integrated mean
fluorescence intensity (iMFI) of BAFF-R, CD38, CD73, and IL-21R, but higher iMFI
of CD95, CD11c, TLR9, PD-1, and CD122. Compared to switched memory B cells, IgM
memory B cells had higher iMFI of BAFF-R, PD-1, IL-21R, TLR9, and CD122, but
lower iMFI of CD38, CD95, and CD73. Four days after receiving the CpG/cytokine
cocktail, higher frequencies of IgM than switched memory B cells-and these in
turn greater than naive cells-proliferated and differentiated to antibody
secreting cells. At this time point, a small percentage (median of 7.6%) of
stimulated IgM memory B cells changed isotype to IgG. Thus, among the
heterogeneous population of human circulating IgM memory B cells a subset is
capable of a rapid functional response to a CpG/cytokine stimulus in vitro.
PMID- 26439741
TI - Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based
Nested Case-Control Study.
AB - BACKGROUND: A cross-sectional study has reported that nickel allergy is
associated with endometriosis. However, causal studies of this association are
limited. OBJECTIVE: The objective of this study was to compare the prevalence of
nickel allergy in women with and without endometriosis. METHODS: We used a
National Health Insurance Service (NHIS) sample cohort dataset that included
approximately 1 million individuals from South Korea; the data were obtained
between January 01, 2002, and December 31, 2013. We selected the endometriosis
group according to diagnosis code (N80.X), surgery codes, and drug codes during
the years 2009~2013. The controls were randomly matched to the endometriosis
patients at a ratio of 4:1 by age and socioeconomic status. Patients with nickel
allergy were defined in the cohort dataset as those with a simultaneous diagnosis
code (L23.0) and patch test code during 2002~2008. RESULTS: In total, 4,985 women
were selected from the NHIS cohort database and divided into an endometriosis
group (997 women) and a control group (3,988 women). The number of patients with
nickel allergy in the endometriosis group was eight (0.8%), and that in the
control group was thirteen (0.3%). After adjustment for age and socioeconomic
status, the rate of nickel allergy in was higher in the endometriosis group than
in the control group [odds ratio: 2.474; 95% confidence interval: 1.023~5.988; p
= 0.044]. CONCLUSIONS: We found that nickel allergy is a risk factor for
endometriosis.
PMID- 26439740
TI - Construction of a High-Density Genetic Map and Quantitative Trait Locus Mapping
in the Sea Cucumber Apostichopus japonicus.
AB - Genetic linkage maps are critical and indispensable tools in a wide range of
genetic and genomic research. With the advancement of genotyping-by-sequencing
(GBS) methods, the construction of a high-density and high-resolution linkage
maps has become achievable in marine organisms lacking sufficient genomic
resources, such as echinoderms. In this study, high-density, high-resolution
genetic map was constructed for a sea cucumber species, Apostichopus japonicus,
utilizing the 2b-restriction site-associated DNA (2b-RAD) method. A total of 7839
markers were anchored to the linkage map with the map coverage of 99.57%, to our
knowledge, this is the highest marker density among echinoderm species. QTL
mapping and association analysis consistently captured one growth-related QTL
located in a 5 cM region of linkage group (LG) 5. An annotated candidate gene,
retinoblastoma-binding protein 5 (RbBP5), which has been reported to be an
important regulator of cell proliferation, was recognized in the QTL region. This
linkage map represents a powerful tool for research involving both fine-scale QTL
mapping and marker assisted selection (MAS), and will facilitate chromosome
assignment and improve the whole-genome assembly of sea cucumber in the future.
PMID- 26439742
TI - Correction: Pirfenidone for Idiopathic Pulmonary Fibrosis: A Systematic Review
and Meta-Analysis.
PMID- 26439743
TI - Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context.
AB - Bile acids have recently been demonstrated as molecules with endocrine activities
controlling several physiological functions such as immunity and glucose
homeostases. They act mainly through two receptors, the nuclear receptor Farnesol
X-Receptor alpha (FXRalpha) and the G-protein coupled receptor (TGR5). These
recent studies have led to the idea that molecules derived from bile acids (BAs)
and targeting their receptors must be good targets for treatment of metabolic
diseases such as obesity or diabetes. Thus it might be important to decipher the
potential long term impact of such treatment on different physiological
functions. Indeed, BAs have recently been demonstrated to alter male fertility.
Here we demonstrate that in mice with overweight induced by high fat diet, BA
exposure leads to increased rate of male infertility. This is associated with the
altered germ cell proliferation, default of testicular endocrine function and
abnormalities in cell-cell interaction within the seminiferous epithelium. Even
if the identification of the exact molecular mechanisms will need more studies,
the present results suggest that both FXRalpha and TGR5 might be involved. We
believed that this work is of particular interest regarding the potential
consequences on future approaches for the treatment of metabolic diseases.
PMID- 26439745
TI - Up-regulation of Activation Markers on Basophils in Patients with
Papuloerythroderma.
PMID- 26439744
TI - Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are
Associated with Non-Alcoholic Fatty Liver Disease.
AB - BACKGROUND: Fatty liver is a major cause of obesity-related morbidity and
mortality. The aim of this study was to identify early metabolic alterations
associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and
women (n = 52) with and without NAFLD. METHODS: Hepatic fat content was measured
using proton magnetic resonance spectroscopy (1H MRS). Serum samples were
analyzed using a nuclear magnetic resonance (NMR) metabolomics platform. Global
gene expression profiles of adipose tissues and skeletal muscle were analyzed
using Affymetrix microarrays and quantitative PCR. Muscle protein expression was
analyzed by Western blot. RESULTS: Increased branched-chain amino acid (BCAA),
aromatic amino acid (AAA) and orosomucoid were associated with liver fat
accumulation already in its early stage, independent of sex, obesity or insulin
resistance (p<0.05 for all). Significant down-regulation of BCAA catabolism and
fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD
group (p<0.001for all), whereas no aberrant gene expression in the skeletal
muscle was found. Reduced BCAA catabolic activity was inversely associated with
serum BCAA and liver fat content (p<0.05 for all). CONCLUSIONS: Liver fat
accumulation, already in its early stage, is associated with increased serum
branched-chain and aromatic amino acids. The observed associations of decreased
BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA
concentration with liver fat content suggest that adipose tissue dysfunction may
have a key role in the systemic nature of NAFLD pathogenesis.
PMID- 26439746
TI - Metabolic abnormalities linked to an increased cardiovascular risk are associated
with high-grade prostate cancer: a single biopsy cohort analysis.
AB - BACKGROUND: Smoking, hypertension, abdominal obesity and metabolic abnormalities
have been considered individual factors involved in prostate cancer (PCa)
pathogenesis. All of these factors are used to define the individual
cardiovascular risk (CVR). The aim of our study was to evaluate the association
between CVR and PCa diagnosis and grade among a consecutive series of men
undergoing prostate biopsy. METHODS: From 2010 onwards, consecutive patients
undergoing 12-core prostate biopsy were enrolled. Body mass index was measured
before the biopsy. Blood samples were collected and tested for: PSA, fasting
glucose, triglycerides and high-density lipoproteins. Blood pressure was also
recorded. Metabolic syndrome was defined according to the Adult Treatment Panel
III and CVR according to the European Association of Cardiologist Guidelines. We
evaluated the association between CVR and PCa biopsy Gleason score using logistic
regression analyses. RESULTS: Five hundred and eighty-four patients were
enrolled. Four hundred and six patients (70%) presented a moderate/high CVR. Two
hundred and thirty-seven (40.6%) patients had cancer on biopsy; 157 with
moderate/high CVR and 80 with low/no CVR (P=0.11). Out of the 237 patients with
PCa, 113 had a Gleason score 6 and 124 a Gleason score ?7. Out of them, 92/124
(75%) presented a moderate/high CVR (P=0.004). Moderate/high CVR was not
associated with an increased risk of PCa (odds ratio (OR): 0.741, confidence
interval (CI): 0.474-1.156; P=0.186) but with an increased risk of Gleason score
?7 (OR: 2.154, CI: 1.076-4.314; P=0.030). CONCLUSIONS: In our study, a
moderate/high CVR is associated with an increased risk of a high-grade Gleason
score when PCa is diagnosed on biopsy. Although these results should be confirmed
in multicentre studies, patients with moderate/high CVR should be carefully
evaluated for PCa diagnosis.
PMID- 26439747
TI - Preoperative low serum testosterone is associated with high-grade prostate cancer
and an increased Gleason score upgrading.
AB - BACKGROUND: To compare histological feature of prostate cancer (PCa) according
androgenic status in patients who underwent radical prostatectomy (RP). METHODS:
Between March 2007 and September 2013, we prospectively analysed 937 patients who
were referred to our centre for RP. Clinical, pathological and biological data
have been prospectively collected. Preoperative total testosterone (TT) and
bioavailable testosterone (BT) serum determinations were carried out. The
threshold for low serum testosterone was set at TT<3 ng/ml. Preoperative PSA
value was registered. Gleason score (GS) and predominant Gleason pattern were
determined in prostate biopsies and in prostate tissue specimens, crosschecked by
two uro-pathologists. RESULTS: Nine hundred and thirty-seven consecutive patients
were included. In all, 14.9% patients had low TT in the population. An exact
match between biopsy and prostate specimens in GS grading was observed for 50.6%
patients (n=474). Also, 40.9% of all patients were upgraded (n=383): 45.3% (n=63)
in low serum testosterone patients and 40.1% (n=320) in normal serum testosterone
patients. For prostate specimens, the proportion of patients with predominant
Gleason pattern 4 was higher in patients with low TT compared with normal TT
(41.7% vs 29.1%, P=0.0029). In all, 20.1% were upgraded from predominant Gleason
pattern 3 on biopsies specimen to predominant Gleason 4 pattern on the prostate
specimen in patients with low TT, whereas 11.6% were upgraded for normal TT
patients (P=0.002). CONCLUSIONS: Low serum testosterone is an independent risk
factor for predominant Gleason pattern 4 on prostate specimen after RP and for
upgrading from low- to high-grade cancer between prostate needle biopsies and RP
specimen. This observation should be taken into account in localised PCa
management, especially for active surveillance or when a nerve-sparing approach
is considered.
PMID- 26439748
TI - A higher order visual neuron tuned to the spatial amplitude spectra of natural
scenes.
AB - Animal sensory systems are optimally adapted to those features typically
encountered in natural surrounds, thus allowing neurons with limited bandwidth to
encode challengingly large input ranges. Natural scenes are not random, and
peripheral visual systems in vertebrates and insects have evolved to respond
efficiently to their typical spatial statistics. The mammalian visual cortex is
also tuned to natural spatial statistics, but less is known about coding in
higher order neurons in insects. To redress this we here record intracellularly
from a higher order visual neuron in the hoverfly. We show that the cSIFE neuron,
which is inhibited by stationary images, is maximally inhibited when the slope
constant of the amplitude spectrum is close to the mean in natural scenes. The
behavioural optomotor response is also strongest to images with naturalistic
image statistics. Our results thus reveal a close coupling between the inherent
statistics of natural scenes and higher order visual processing in insects.
PMID- 26439750
TI - Structure, viscoelasticity, and interfacial dynamics of a model polymeric
bicontinuous microemulsion.
AB - We have systematically studied the equilibrium structure and dynamics of a
polymeric bicontinuous microemulsion (BMUE) composed of poly(cyclohexylethylene)
(PCHE), poly(ethylene) (PE), and a volumetrically symmetric PCHE-PE diblock
copolymer, using dynamic mechanical spectroscopy, small angle X-ray and neutron
scattering, and transmission electron microscopy. The BMUE was investigated over
an 80 degrees C temperature range, revealing a structural evolution and a
rheological response not previously recognized in such systems. As the
temperature is reduced below the point associated with the lamellar-disorder
transition at compositions adjacent to the microemulsion channel, the interfacial
area per chain of the BMUE approaches that of the neat (undiluted) lamellar
diblock copolymer. With increasing temperature, the diblock-rich interface swells
through homopolymer infiltration. Time-temperature-superposed linear dynamic data
obtained as a function of frequency show that the viscoelastic response of the
BMUE is strikingly similar to that of the fluctuating pure diblock copolymer in
the disordered state, which we associate with membrane undulations and the
breaking and reforming of interfaces. This work provides new insights into the
structure and dynamics that characterize thermodynamically stable BMUEs in the
limits of relatively weak and strong segregation.
PMID- 26439749
TI - A Group of ent-Kaurane Diterpenoids Inhibit Hedgehog Signaling and Induce Cilia
Elongation.
AB - The Hedgehog (Hh) signaling pathway plays important roles in the tumorigenesis of
multiple cancers and is a key target for drug discovery. In a screen of natural
products extracted from Chinese herbs, we identified eight ent-Kaurane
diterpenoids and two triterpene dilactones as novel Hh pathway antagonists.
Epistatic analyses suggest that these compounds likely act at the level or
downstream of Smoothened (Smo) and upstream of Suppressor of Fused (Sufu). The
ent-Kauranoid-treated cells showed elongated cilia, suppressed Smo trafficking to
cilia, and mitotic defects, while the triterpene dilactones had no effect on the
cilia and ciliary Smo. These ent-Kaurane diterpenoids provide new prototypes of
Hh inhibitors, and are valuable probes for deciphering the mechanisms of Smo
ciliary transport and ciliogenesis.
PMID- 26439751
TI - Promising wet chemical strategies to synthesize Cu nanowires for emerging
electronic applications.
AB - Copper nanowires (Cu NWs) are of particular interest for application as
transparent and flexible conducting electrodes in 'see-through' and/or
'deformable' future electronics due to their excellent electrical, optical, and
mechanical properties. It is necessary to develop reliable and facile methods to
produce well-defined Cu NWs prior to their full exploitation. Among the wide
variety of methods available to generate Cu NWs, solution-based synthesis routes
are considered to be a promising strategy because of several advantages including
fewer constraints on the selection of precursors, the solvent and reaction
conditions, and the feasibility of large-scale low-cost production. Here, we
provide a thorough review of various recently developed synthetic methodologies
to obtain Cu NWs, with particular emphasis on wet chemical synthesis approaches
including a hydrothermal route, reduction of metal precursors, and catalytic
synthesis. The emerging applications of Cu NWs including transparent electrodes
and flexible/stretchable electronics are also discussed, followed by brief
comments on the remaining challenges and future research perspectives.
PMID- 26439752
TI - The composition and function of the striatin-interacting phosphatases and kinases
(STRIPAK) complex in fungi.
AB - The striatin-interacting phosphatases and kinases (STRIPAK) complex is a highly
conserved eukaryotic protein complex that was recently described for diverse
animal and fungal species. Here, we summarize our current knowledge about the
composition and function of the STRIPAK complex from the ascomycete Sordaria
macrospora, which we discovered by investigating sexually sterile mutants (pro),
having a defect in fruiting body development. Mass spectrometry and yeast two
hybrid analysis defined core subunits of the STRIPAK complex, which have
structural homologs in animal and other fungal organisms. These subunits (and
their mammalian homologs) are PRO11 (striatin), PRO22 (STRIP1/2), SmMOB3 (Mob3),
PRO45 (SLMAP), and PP2AA, the structural, and PP2Ac, the catalytic subunits of
protein phosphatase 2A (PP2A). Beside fruiting body formation, the STRIPAK
complex controls vegetative growth and hyphal fusion in S. macrospora. Although
the contribution of single subunits to diverse cellular and developmental
processes is not yet fully understood, functional analysis has already shown that
mammalian homologs are able to substitute the function of distinct fungal STRIPAK
subunits. This underscores the view that fungal model organisms serve as useful
tools to get a molecular insight into cellular and developmental processes of
eukaryotes in general. Future work will unravel the precise localization of
single subunits within the cell and decipher their STRIPAK-related and STRIPAK
independent functions. Finally, evidence is accumulating that there is a
crosstalk between STRIPAK and various signaling pathways, suggesting that
eukaryotic development is dependent on STRIPAK signaling.
PMID- 26439753
TI - Quantifying the Ototoxicity of Mitomycin: Before versus after Myringotomy.
AB - OBJECTIVES: Recent research has focused on mitomycin C (MMC) application as a
means to circumvent complications that arise when using ventilation tubes during
myringotomy. This study has two aims: (1) to synergize the current literature to
create a standardized clinical approach for using MMC, and (2) to determine at
which point during the myringotomy the application of MMC proves the safest
(i.e., before or after incision). METHODS: We measured the auditory brainstem
response (ABR) and distortion product otoacoustic emissions (DPOAE) in 9 female
chinchillas to determine whether applying MMC before or after incision was also
the safest. The tests were then repeated on days 3, 10 and 17. RESULTS: The
change in the ABR thresholds from baseline was greater in the experimental than
in the control group; however, after stratification, the 'after' group
experienced a statistically significant change (19.38 +/- 8.26) on day 17,
whereas the 'before' group did not (2.00 +/- 3.26; p = 0.003). No such changes
were seen with DPOAE testing. CONCLUSIONS: Mitomycin is less ototoxic to the
middle ear when applied before myringotomy is done. We recommend future studies
to apply the clinical approach we have designed to standardize its use in
selected cases.
PMID- 26439754
TI - Fear of hypoglycemia in adults with type 1 diabetes: impact of therapeutic
advances and strategies for prevention - a review.
AB - PURPOSE: This review summarizes the current state of the science related to fear
of hypoglycemia (FOH) in adults with type 1 diabetes. Fear of hypoglycemia is a
critical deterrent to diabetes self-management, psychological well-being, and
quality of life. We examine the influence of contemporary treatment regimens,
technology, and interventions to identify gaps in knowledge and opportunities for
research and practice. BASIC PROCEDURES: A literature search was conducted of
MEDLINE, PsycINFO, and EMBASE. Fifty-three studies that examined fear of
hypoglycemia were included. MAIN FINDINGS: Fear of hypoglycemia influences
diabetes management and quality of life. Gender and age differences exist in
experiences and responses. Responses vary from increased vigilance to potentially
immobilizing distress. Fear of hypoglycemia is greater at night and may
contribute to poor sleep quality. Strategies to reduce fear of hypoglycemia have
had varying success. Newer technologies hold promise but require further
examination. CONCLUSIONS: Fear of hypoglycemia remains a problem, despite
advances in technology, insulin analogs, and evidence-based diabetes management.
Clinical care should consistently include assessment for its influence on
diabetes self-management and psychological health. Further research is needed
regarding the influence of newer technologies and individualized strategies to
reduce fear of hypoglycemia while maintaining optimal glucose control.
PMID- 26439755
TI - Applicability of modified Glasgow Prognostic Score in the assessment of elderly
patients with cancer: A pilot study.
AB - OBJECTIVES: To evaluate the relationship between inflammatory parameters through
the modified Glasgow Prognostic Score (mGPS) and other clinical characteristics
of elderly patients with cancer, including frailty evaluated by the Edmonton
Frailty Scale (EFS). MATERIALS AND METHODS: We included patients from the
oncology service at Faculdade de Medicina do ABC with a confirmed diagnosis of
solid tumor aged 65 years or more at diagnosis. Patients were assessed by
applying the translated and validated to Portuguese version of the EFS and also
had blood sample collection for the evaluation of C-reactive protein (CRP) and
albumin for calculation of the mGPS. RESULTS: We included 52 patients of both
sexes, with median age of 72.5 years, of these 67.3% had localized disease and
32.7% metastatic disease. The mGPS presented 17.3% of high-risk patients. The
frailty evaluated by EFS occurred in 57.6% of patients. Patients with both
abnormal parameters (CRP and albumin) in the mGPS had significantly higher scores
on EFS when compared to those with no change (6 vs. 9.56 points, p=0.021). The
mGPS correlated also with clinical staging (p=0.019) and performance status
(p=0.039). CONCLUSIONS: Inflammatory parameters correlate significantly with
frailty, more advanced clinical stage and poor functional status.
PMID- 26439756
TI - Early intervention and child physical health: Evidence from a Dublin-based
randomized controlled trial.
AB - This article investigates the impact of an early intervention program, which
experimentally modifies the parenting and home environment of disadvantaged
families, on child physical health in the first 3 years of life. We recruited and
randomized 233 (115 intervention, 118 control) pregnant women from a
socioeconomically disadvantaged community in Dublin, Ireland into an intervention
or control group. The treatment includes regular home visits commencing
antenatally and an additional parenting course commencing at 2 years. Maternal
reports of child health are assessed at 6, 12, 18, 24, and 36 months. Treatment
effects are estimated using permutation testing to account for small sample size,
inverse probability weighting to account for differential attrition, and both the
stepdown procedure and an indices approach to account for multiple hypothesis
testing. Following adjustment for multiple testing and attrition, we observe a
positive and statistically significant main treatment effect for wheezing/asthma.
The intervention group are 15.5 percentage points (pp) less likely to require
medical attention for wheezing/asthma compared to the control group. Subgroup
analysis reveals more statistically significant adjusted treatment effects for
boys than girls regarding fewer health problems (d=0.63), accidents (23.9pp), and
chest infections (22.8-37.9pp). Our results suggest that a community-based home
visiting program may have favorable impacts on early health conditions.
PMID- 26439757
TI - Overweight trends among Polish schoolchildren before and after the transition
from communism to capitalism.
AB - This study aims to reveal the secular trends in body mass index (BMI) and the
prevalence of overweight and obesity among Polish schoolchildren between the
years 1966-2012, during which intense socio-political changes took place. Four
surveys were conducted in several districts of Poland looking at 69,746
schoolchildren aged 7-18. Significant increase in mean BMI as well as in the
prevalence of overweight and obesity was observed. During this time the highest
increase in both mean BMI and excess weight was observed between 1988 and 2012,
i.e. after the political transformation, resulting in the improvement of living
conditions. However, with respect to girls in late adolescence, between these
years, the mean BMI as well as the prevalence of overweight were leveling off,
while the percentage of boys with excess body fat in the same developmental
category significantly increased in 2012. In the years 1966-1978 and 1978-1988
the pattern of changes in the prevalence of overweight and obesity reflected the
social and economic circumstances, i.e. temporary economic improvements, or
deepening political crises and food shortage. In conclusion, the weight status of
schoolchildren strongly reflects socio-political changes that took place in
Poland, as well as in most of the Central European countries in the last half
century.
PMID- 26439758
TI - Paraumbilical fat graft for the correction of contour deformity following
parotidectomy and prevention of Frey syndrome.
AB - Following parotidectomy, patients develop retromandibular hollowing. A case
series of patients for whom a free paraumbilical graft was used to reconstruct
the parotid bed defect is presented here. This graft is harvested through a
supra/sub-umbilical or suprapubic incision. Over-correction of approximately 50%
is required due to atrophy and resorption with time. The graft is harvested with
the overlying dermis and the graft should not be filleted, as this can cause
necrosis. An antibiotic membrane is placed between the graft and the underlying
bed and the graft is secured with Vicryl sutures. Since 1997, 130 patients have
been treated successfully with this method. Regarding complications, nine
patients developed a seroma, four developed a haematoma, two suffered graft
liquefaction, and one suffered an infection with frank suppuration and loss of
the graft. However, no complications have been noted in the most recent 70
patients. The incidence of Frey syndrome also appeared to be reduced. The
paraumbilical fat graft appears to be a successful and reliable method of
correcting facial defects after a superficial or total parotidectomy. The graft
can also be used to correct temporal defects and has the added advantage of
reducing Frey syndrome.
PMID- 26439759
TI - Evaluation of the level of progression of extracapsular spread for cervical lymph
node metastasis in oral squamous cell carcinoma.
AB - Only a few reports on the level of progression of extracapsular spread (ECS) have
been published. The aim of this study was to evaluate the efficacy of the level
of progression of ECS in identifying those patients with oral squamous cell
carcinoma (OSCC) at a high risk of recurrence who would benefit most from the
intensification of adjuvant therapy. The level of progression of ECS for cervical
lymph node metastasis in OSCC was divided into three types (A-C), and their
relationships with patient prognosis were examined. ECS was observed in 87 of 441
patients with OSCC. The recurrence rate in patients with type C, which was
defined as macroscopic tumour invasion into perinodal fat or muscle tissue, was
high (69.8%), with 13 cases of death due to distant metastasis. The 3-year
disease-specific survival rate for patients with type C was 49.0% and these
patients also had a significantly poorer prognosis (P<0.01). The results of the
multivariate analysis suggested that the prognosis of ECS in OSCC patients was
associated with the level of progression of ECS, especially type C (P<0.01).
Overall, the results of this study suggest that the level of progression of ECS
is a useful prognostic factor in OSCC patients.
PMID- 26439760
TI - Ultramicro-trauma in the endometrial-myometrial junctional zone and pale cell
migration in adenomyosis.
AB - OBJECTIVE: To determine if ultrastructural tissue trauma occurs in the junctional
zone in uteri in adenomyosis. DESIGN: A case-control experimental study. SETTING:
Endometriosis research center. PATIENT(S): Twelve uteri with adenomyosis, and 9
uteri without adenomyosis, were gained during laparoscopy-assisted vaginal
hysterectomy. INTERVENTION(S): Transmission electron microscopic study of the
junctional zone, as well as immunohistochemical staining for epithelial cadherin,
and van Gieson staining and immunofluorescence for CD45 and CD68. MAIN OUTCOME
MEASURE(S): Analysis of the electron microscopy photos and the immunoreactive
scores of the staining. RESULT(S): The inner myometrial muscle fibers were
diversely arranged in adenomyosis; they were parallel to the basal endometrial
glands in nonadenomyosis. Nuclear membrane infolding of the basal glandular
epithelium and the disruption of the interface between basal endometrium and
inner myometrium in adenomyosis (but not in nonadenomyosis) were evident.
Intraepithelial pale cells were seen in the basal endometrial glands in both
groups, but they lacked CD45 and CD68 expression. They were seen actively
migrating into the stroma in adenomyosis only. CONCLUSION(S): The myofiber
disarray in the inner myometrium, and the nuclear membrane irregularities in
adenomyosis, are evidence for ultramicro-trauma in adenomyosis. The migrating
nonleukocytic pale cells may be involved in pathogenesis of adenomyosis.
PMID- 26439761
TI - The conversation.
PMID- 26439762
TI - Delayed orgasm and anorgasmia.
AB - Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty,
delay in, or absence of attaining orgasm after sufficient sexual stimulation,
which causes personal distress. Delayed orgasm and anorgasmia are associated with
significant sexual dissatisfaction. A focused medical history can shed light on
the potential etiologies, which include medications, penile sensation loss,
endocrinopathies, penile hyperstimulation, and psychological etiologies.
Unfortunately, there are no excellent pharmacotherapies for delayed
orgasm/anorgasmia, and treatment revolves largely around addressing potential
causative factors and psychotherapy.
PMID- 26439763
TI - Longitudinal associations of neighborhood socioeconomic characteristics and
alcohol availability on drinking: Results from the Multi-Ethnic Study of
Atherosclerosis (MESA).
AB - Neighborhood socioeconomic characteristics and alcohol availability may affect
alcohol consumption, but adequate longitudinal research to support these
hypotheses does not exist. We used data from the Multi-Ethnic Study of
Atherosclerosis (MESA) (N = 6163) to examine associations of changes in
neighborhood socioeconomic status (SES) and alcohol outlet density, with current,
weekly, and heavy daily alcohol consumption in hybrid effects models. We also
examined whether these associations were moderated by gender, race/ethnicity, and
income. Increases in neighborhood SES were associated with decreases in the
probability of current alcohol use after adjustment for age, gender,
race/ethnicity, individual SES, marital status and time since baseline
[probability ratio (PR) per SD increase in neighborhood SES = 0.96, 95%
confidence interval (CI) (0.96.0.99)]. Increases in liquor store densities were
associated with increases in weekly alcohol consumption [ratio of weekly drinks
per SD increase in outlet density = 1.07, 95% CI (1.01.1.05) for men, PR = 1.11,
95% CI (1.01.1.21) for women]. Relationships between current alcohol use and
neighborhood SES and between weekly beer consumption and neighborhood SES were
generally stronger among those with higher incomes. Neighborhood socioeconomic
context and the availability of alcohol may be important for understanding
patterns of alcohol use over time, and for targeting interventions and policies
to reduce harmful alcohol use.
PMID- 26439764
TI - The downside of tobacco control? Smoking and self-stigma: A systematic review.
AB - OBJECTIVE: Little is known about the consequences of tobacco smoking stigma on
smokers and how smokers may internalize smoking-related stigma. This review
summarizes existing literature on tobacco smoking self-stigma, investigating to
what extent smokers are aware of negative stereotypes, agree with them and apply
them to themselves. METHODS: We carried out a systematic search of Pubmed/Web of
Science/PsycInfo databases for articles related to smoking self-stigma through
June 2013. Reference lists and citations of included studies were also checked
and experts were contacted. After screening articles for inclusion/exclusion
criteria we performed a quality assessment and summarized findings according to
the stages of self-stigma as conceptualized in Corrigan's progressive model of
self-stigma (aware, agree, apply and harm). Initial searches yielded 570
articles. RESULTS: Thirty of these articles (18 qualitative and 12 quantitative
studies) met criteria for our review. Awareness of smoking stigma was virtually
universal across studies. Coping strategies for smoking stigma and the degree to
which individuals who smoke internalized this stigma varied both within and
across studies. There was considerable variation in positive, negative, and non
significant consequences associated with smoking self-stigma. Limited evidence
was found for subgroup differences in smoking-related stigma. CONCLUSION: While
there is some evidence that smoking self-stigma leads to reductions in smoking,
this review also identified significant negative consequences of smoking self
stigma. Future research should assess the factors related to differences in how
individuals respond to smoking stigma. Public health strategies which limit the
stigmatization of smokers may be warranted.
PMID- 26439765
TI - A Naturally Occurring Repeat Protein with High Internal Sequence Identity Defines
a New Class of TPR-like Proteins.
AB - Linear repeat proteins often have high structural similarity and low (~25%)
pairwise sequence identities (PSI) among modules. We identified a unique P.
anserina (Pa) sequence with tetratricopeptide repeat (TPR) homology, which
contains longer (42 residue) repeats (42PRs) with an average PSI >91%. We
determined the crystal structure of five tandem Pa 42PRs to 1.6 A, and examined
the stability and solution properties of constructs containing three to six Pa
42PRs. Compared with 34-residue TPRs (34PRs), Pa 42PRs have a one-turn extension
of each helix, and bury more surface area. Unfolding transitions shift to higher
denaturant concentration and become sharper as repeats are added. Fitted Ising
models show Pa 42PRs to be more cooperative than consensus 34PRs, with increased
magnitudes of intrinsic and interfacial free energies. These results demonstrate
the tolerance of the TPR motif to length variation, and provide a basis to
understand the effects of helix length on intrinsic/interfacial stability.
PMID- 26439766
TI - Active-State Structures of a Small Heat-Shock Protein Revealed a Molecular Switch
for Chaperone Function.
AB - Small heat-shock proteins (sHsps) maintain cellular homeostasis by binding to
denatured client proteins to prevent aggregation. Numerous studies indicate that
the N-terminal domain (NTD) of sHsps is responsible for binding to client
proteins, but the binding mechanism and chaperone activity regulation remain
elusive. Here, we report the crystal structures of the wild-type and mutants of
an sHsp from Sulfolobus solfataricus representing the inactive and active state
of this protein, respectively. All three structures reveal well-defined NTD, but
their conformations are remarkably different. The mutant NTDs show disrupted
helices presenting a reformed hydrophobic surface compatible with recognizing
client proteins. Our functional data show that mutating key hydrophobic residues
in this region drastically altered the chaperone activity of this sHsp. These
data suggest a new model in which a molecular switch located in NTD facilitates
conformational changes for client protein binding.
PMID- 26439767
TI - Charge-Triggered Membrane Insertion of Matrix Metalloproteinase-7, Supporter of
Innate Immunity and Tumors.
AB - Matrix metalloproteinase-7 (MMP-7) sheds signaling proteins from cell surfaces to
activate bacterial killing, wound healing, and tumorigenesis. The mechanism
targeting soluble MMP-7 to membranes has been investigated. Nuclear magnetic
resonance structures of the zymogen, free and bound to membrane mimics without
and with anionic lipid, reveal peripheral binding to bilayers through
paramagnetic relaxation enhancements. Addition of cholesterol sulfate partially
embeds the protease in the bilayer, restricts its diffusion, and tips the active
site away from the bilayer. Its insertion of hydrophobic residues organizes the
lipids, pushing the head groups and sterol sulfate outward toward the enzyme's
positive charge on the periphery of the enlarged interface. Fluorescence probing
demonstrates a similar mode of binding to plasma membranes and internalized
vesicles of colon cancer cells. Binding of bilayered micelles induces allosteric
activation and conformational change in the auto-inhibitory peptide and the
adjacent scissile site, illustrating a potential intermediate in the activation
of the zymogen.
PMID- 26439769
TI - A morphometric study on flexor carpi radialis muscle of the forearm: A cadaveric
study.
AB - BACKGROUND: Flexor carpi radialis (FCR) is frequently used in reconstruction
procedures involving the hand and wrist regions. Despite having tremendous
clinical significance, very few studies have been conducted on the heterogeneity
of the FCR. Its surgical importance in grafting techniques and tendon transfers
prompted us to study the morphometry of FCR. MATERIALS AND METHODS: In this
study, we used 37 upper limbs (25 right and 12 left sides) of formalin embalmed
cadavers. FCR was neatly dissected in all upper limbs to measure its total
length, muscle belly length, tendon length, width of muscle belly at proximal and
distal ends, width of tendon at proximal and distal ends. RESULTS: Average total
length of the muscle, muscle belly length, tendon length, width of muscle belly
at the proximal end, width of muscle belly at the distal end, width of tendon at
the proximal end, width of tendon at the distal end were 27.1 +/- 2.13, 12.38 +/-
2.23, 14.99 +/- 2.36, 1.99 +/- 0.72, 1.59 +/- 0.48, 1.59 +/- 0.48 and 0.42 +/-
0.12 cm, respectively. Ratio of mean muscle length and tendon length, ratio of
mean tendon length and total length were found to be 0.45 +/- 0.07 and 0.55 +/-
0.07, respectively. No noted variations were observed in the proximal and distal
attachments of the FCR muscle. CONCLUSION: Morphometric data of FCR reported
increases the existing knowledge on the heterogeneity of FCR morphology, and
further forms an anatomic basis while designing/elevating the graft in certain
surgical procedures in hand and wrist regions.
PMID- 26439768
TI - Structure of AcrH-AopB Chaperone-Translocator Complex Reveals a Role for Membrane
Hairpins in Type III Secretion System Translocon Assembly.
AB - Type III secretion systems (T3SSs) are adopted by pathogenic bacteria for the
transport of effector proteins into host cells through the translocon pore
composed of major and minor translocator proteins. Both translocators require a
dedicated chaperone for solubility. Despite tremendous efforts in the past,
structural information regarding the chaperone-translocator complex and the
topology of the translocon pore have remained elusive. Here, we report the
crystal structure of the major translocator, AopB, from Aeromonas hydrophila AH-1
in complex with its chaperone, AcrH. Overall, the structure revealed unique
interactions between the various interfaces of AopB and AcrH, with the N-terminal
"molecular anchor" of AopB crossing into the "N-terminal arm" of AcrH. AopB
adopts a novel fold, and its transmembrane regions form two pairs of helical
hairpins. From these structural studies and associated cellular assays, we
deduced the topology of the assembled T3SS translocon; both termini remain
extracellular after membrane insertion.
PMID- 26439770
TI - In vitro evaluation of gammadelta T cells regulatory function in Behcet's disease
patients and healthy controls.
AB - CD8-positive gammadelta T lymphocytes (GDCD8(+)) are specifically increased in
peripheral blood of Behcet's disease (BD) patients. GDCD8(+) have shown a T
regulatory (Treg) function in autoimmune experimental models, human tumor
infiltrates and intestinal intraepithelial lymphocytes from celiac patients. The
aim of this study was to evaluate the Treg function of GDCD8(+) and GDCD8(-),
freshly isolated from peripheral blood, in comparison to CD4(+)CD25(high)
naturally occurring Treg cells (nTreg) in BD and healthy controls (HC). We tested
their suppressive activity on CD4(+)CD25(-) T effector cells (Teff) proliferation
by a CFSE dilution protocol, after suboptimal activation with anti-CD3, in the
absence or presence of IL-2. Furthermore, secreted cytokines and suppressive
latency associated peptide (LAP)-TGFbeta surface upregulation were determined
after GD activation. We found that Vdelta1 chains contribution to GDCD8(+) was
higher in BD than in HC, but neither GDCD8(+) nor GDCD8(-); (i) suppressed Teff
proliferation, (ii) expressed LAP-TGFbeta (iii) nor secreted IL-10, in either
group. Moreover, GD presented a proinflammatory cytokine profile, mainly
producing IFNgamma and TNFalpha, in contrast to nTregs. In conclusion, peripheral
GD could contribute more to the dysregulation of TH1 type of cytokines than to
exerting a Treg function in BD.
PMID- 26439771
TI - Electrical Conductivity and Strong Luminescence in Copper Iodide Double Chains
with Isonicotinato Derivatives.
AB - Direct reactions between CuI and isonicotinic acid (HIN) or the corresponding
esters, ethyl isonicotinate (EtIN) or methyl isonicotinate (MeIN), give rise to
the formation of the coordination polymers [CuI(L)]n with L=EtIN (1), MeIN (2)
and HIN (3). Polymers 1-3 show similar structures based on a CuI double chain in
which ethyl-, methyl isonicotinate or isonicotinic acid are coordinated as
terminal ligands. Albeit, their supramolecular architecture differs considerably,
affecting the distances and angles of the central CuI double chains and thereby
their physical properties. Hence, the photoluminescence shows remarkable
differences; 1 and 2 show a strong yellow emission, whereas 3 displays a weak
emission; and 1 and 2 are semiconductors with moderate room temperature
conductivities, whereas 3 has increased electrical conductivity up to 3*10(-3) S
cm(-1) . Additionally, 1 and 2 present an irreversible transition to a highly
conducting phase with a conductivity almost 4 orders of magnitude higher and a
quasi-metallic behaviour. Thermogravimetric analysis (TGA) coupled to a mass
spectrometer and magnetic measurements point to a partial thermally induced
oxidation of the carboxylate groups of the ligands with Cu(I) to Cu(0) reduction.
DFT calculations have been carried out to rationalise these observations.
PMID- 26439772
TI - Re: Dijkstra-Eshuis J, Van den Bos TW, Splinter R, Bevers RF, Zonneveld WC,
Putter H, Pelger RC, Voorham-van der Zalm PJ. Effect of preoperative pelvic floor
muscle therapy with biofeedback versus standard care on stress urinary
incontinence and quality of life in men undergoing laparoscopic radical
prostatectomy: A randomised control trial. Neurourol Urodyn. 2015 Feb;34(2):144
50.
PMID- 26439773
TI - Retracted: A new contemporary prostate cancer grading system.
PMID- 26439774
TI - Polymer Cages as Universal Tools for the Precise Bottom-Up Synthesis of Metal
Nanoparticles.
AB - A template synthesis allows the preparation of monodisperse nanoparticles with
high reproducibility and independent from self-assembly requirements. Tailor-made
polymer cages were used for the preparation of nanoparticles, which were made of
cross-linked macromolecules with pendant thiol groups. Gold nanoparticles (AuNPs)
were prepared in the polymer cages in situ, by using different amounts of cages
versus gold. The polymer cages exhibited a certain capacity, below which the
AuNPs could be grown with excellent control over the size and shape. Control
experiments with a linear diblock copolymer showed a continuous increase in the
AuNP size as the gold feed increased. This completely different behavior
regarding the AuNP size evolution was attributed to the flexibility of the
polymer chain depending on cross-linking. Moreover, the polymer cages were
suitable for the encapsulation of AgNPs, PdNPs, and PtNPs by the in situ method.
PMID- 26439776
TI - The Validity and Reliability of Global Positioning Systems in Team Sport: A Brief
Review.
AB - The use of global positioning systems (GPS) has increased dramatically over the
last decade. Using signals from orbiting satellites, the GPS receiver calculates
the exact position of the device and the speed at which the device is moving.
Within team sports GPS devices are used to quantify the external load experienced
by an athlete, allowing coaches to better manage trainings loads and potentially
identify athletes who are overreaching or overtraining. This review aims to
collate all studies that have tested either (or both) the validity or reliability
of GPS devices in a team sport setting, with a particular focus on (a)
measurements of distance, speed, velocities, and accelerations across all
sampling rates and (b) accelerometers, player/body load and impacts in
accelerometer-integrated GPS devices. A comprehensive search of the online
libraries identified 22 articles that fit search criteria. The literature
suggests that all GPS units, regardless of sampling rate, are capable of tracking
athlete's distance during team sport movements with adequate intraunit
reliability. One Hertz and 5Hz GPS units have limitations in their reporting of
distance during high-intensity running, velocity measures, and short linear
running (particularly those involving changes of direction), although these
limitations seem to be overcome during measures recorded during team sport
movements. Ten Hertz GPS devices seem the most valid and reliable to date across
linear and team sport simulated running, overcoming many limitations of earlier
models, whereas the increase to 15Hz GPS devices have had no additional benefit.
PMID- 26439777
TI - Relative Intensity Influences the Degree of Correspondence of Jump Squats and
Push Jerks to Countermovement Jumps.
AB - The aim of this study was to determine the mechanical similarity between push
jerk (PJ) and jump squat (JS) to countermovement jump (CMJ) and further
understand the effect increasing external load may have on this relationship.
Eight physically trained men (age 22 +/- 3; height 176 +/- 7 kg; weight 83 +/- 8
kg) performed an unloaded CMJ followed by JS under a range of loads (10, 25, 35,
and 50% 1RM back squat) and PJ (30, 50, 65, and 75% 1RM push jerk). A portable
force platform and high-speed camera both collecting at 250 Hz were used to
establish joint moments and impulse during the propulsive phase of the movements.
A standard inverse dynamics model was used to determine joint moment and impulse
at the hip, knee, and ankle. Significant correlations (p <= 0.05) were shown
between CMJ knee joint moment and JS knee joint moment at 25% load and PJ knee
joint moment at 30 and 50% load. Significant correlations were also observed
between CMJ knee joint impulse and JS knee joint impulse at 10% load and PJ knee
joint moment at 30 and 65% load. Significant correlation was also observed
between CMJ hip joint impulse and PJ hip joint impulse at 30% load. No
significant joint * load interaction was shown as load increased for either PJ or
JS. Results from the study suggest partial correspondence between PJ and JS to
CMJ, where a greater mechanical similarity was observed between the PJ and CMJ.
This interaction is load and joint dependent where lower relative loads showed
greatest mechanical similarity. Therefore using lower relative loads when
programming may provide a greater transfer of training effect.
PMID- 26439775
TI - Effect of Age, Duration of Exposure, and Dose of Atrazine on Sexual Maturation
and the Luteinizing Hormone Surge in the Female Sprague-Dawley Rat.
AB - Atrazine (ATZ) was administered daily by gavage to pregnant female Sprague Dawley
rats at doses of 0, 6.25, 25 or 50 mg/kg/day, either during gestation, lactation
and post-weaning (G/L/PW cohort) to F1 generation female offspring or only from
postnatal day (PND 21) until five days after sexual maturation (vaginal opening)
when the estrogen-primed, luteinizing hormone (LH) surge was evaluated (PW
cohort). Additional subgroups of F1 females received the vehicle or ATZ from PND
21-133 or from PND 120-133. Slight reductions in fertility and the percentage of
F1 generation pups surviving to PND 21 in the gestationally exposed 50 mg/kg dose
group were accompanied by decreased food intake and body weight of dams and F1
generation offspring. The onset of puberty was delayed in of the F1 generation
G/L/PW females at doses of 25 and 50 mg/kg/day. F1 generation females in the PW
high-dose ATZ group also experienced a delay in the onset of puberty. ATZ had no
effect on peak LH or LH AUC in ovariectomized rats 5 days after sexual
maturation, irrespective of whether the F1 generation females were treated from
gestation onward or only peripubertally. There was no effect of ATZ treatment on
the estrous cycle, peak LH or LH AUC of F1 generation females exposed from
gestation through to PND 133 or only for two weeks from PND 120-133. These
results indicate that developing females exposed to ATZ are not more sensitive
compared to animals exposed to ATZ as young adults.
PMID- 26439778
TI - Acute Physiological Responses to Strongman Training Compared to Traditional
Strength Training.
AB - Strongman training (ST) has become an increasingly popular modality, but data on
physiological responses are limited. This study sought to determine physiological
responses to an ST session compared to a traditional strength exercise training
(RST) session. Ten healthy men (23.6 +/- 27.5 years, 85.8 +/- 10.3 kg)
volunteered in a crossover design, where all participants performed an ST
session, an RST session, and a resting session within 7 days apart. The ST
consisted of sled drag, farmer's walk, 1 arm dumbbell clean and press, and tire
flip at loads eliciting approximately 30 seconds of near maximal effort per set.
The RST consisted of squat, deadlift, bench press, and power clean, progressing
to 75% of 1 repetition maximum. Sessions were equated for approximate total set
duration. Blood lactate and salivary testosterone were recorded immediately
before and after training sessions. Heart rate, caloric expenditure, and
substrate utilization were measured throughout the resting session, both training
protocols and for 80 minutes after training sessions. Analyses were conducted to
determine differences in physiological responses within and between protocols. No
significant changes in testosterone occurred at any time point for either
session. Lactate increased significantly immediately after both sessions. Heart
rate, caloric expenditure, and substrate utilization were all elevated
significantly during ST and RST. Heart rate and fat expenditure were
significantly elevated compared to resting in both sessions' recovery periods;
calorie and carbohydrate expenditures were not. Compared to RST, ST represents an
equivalent physiological stimulus on key parameters indicative of potential
training-induced adaptive responses. Such adaptations could conceivably include
cardiovascular conditioning.
PMID- 26439780
TI - Comparative Effects of Vigorous-Intensity and Low-Intensity Blood Flow Restricted
Cycle Training and Detraining on Muscle Mass, Strength, and Aerobic Capacity.
AB - Traditional high-intensity aerobic training has been shown to improve muscle
protein synthesis and aerobic capacity; however, recent research indicates that
low-intensity aerobic training with blood flow restriction (BFR) may have similar
effects. The purpose of this study was to compare the effects of vigorous
intensity (VI) cycling vs. low-intensity cycling with BFR (LI-BFR) on muscle
mass, strength, and aerobic capacity after training and subsequent detraining.
Thirty-one physically active subjects were assigned to one of 3 groups: VI (n =
10, 60-70% heart rate reserve [HRR]), LI-BFR (n = 11, 30% HRR with BFR at 160-180
mm Hg), and no exercise control (n = 10, no exercise). Subjects in VI and LI-BFR
cycled 3 times per week for 6 weeks (total 18 sessions). Body composition, muscle
mass, strength, and aerobic capacity were measured pre, post, and after 3 weeks
of detraining. A group * time interaction (p = 0.019) effect for both knee
flexion and leg lean mass was found. For both VI and LI-BFR groups, knee flexion
strength was significantly increased between pre and post (p = 0.024, p = 0.01)
and between pre and 3 week-post (p = 0.039, p = 0.003), respectively. For the LI
BFR group, leg lean mass was significantly increased between pre and 3 week-post
(p = 0.024) and between post and 3 week-post (p = 0.013). However, there were no
significant differences between groups for any variables. The LI-BFR elicits an
increase in the knee flexion muscle strength over time similar to the VI. An
increase in the leg lean mass over time was seen in the LI-BFR, but not in VI and
CON.
PMID- 26439781
TI - Time Course of Improvements in Power Characteristics in Elite Development Netball
Players Entering a Full-Time Training Program.
AB - We describe the time course of adaptation to structured resistance training on
entering a full-time high-performance sport program. Twelve international caliber
female netballers (aged 19.9 +/- 0.4 years) were monitored for 18 weeks with
countermovement (CMJ: performed with body weight and 15 kg) and drop jumps (0.35
m box at body weight) at the start of each training week. Performance did not
improve linearly or concurrently with loaded CMJ power improving 11% by Week 5
(effect size [ES] 0.93 +/- 0.72) in contrast, substantial positive changes were
observed for unloaded CMJ power (12%; ES 0.78 +/- 0.39), and CMJ velocity
(unloaded: 7.1%; ES 0.66 +/- 0.34; loaded: 7.5%; ES 0.90 +/- 0.41) by week 7.
Over the investigation duration, large improvements were observed in unloaded CMJ
power (24%; ES 1.45 +/- 1.11) and velocity (12%; ES 1.13 +/- 0.76). Loaded CMJ
power also showed a large improvement (19%; ES 1.49 +/- 0.97) but only moderate
changes were observed for loaded CMJ velocity (8.4%; ES 1.01 +/- 0.67). Jump
height changes in either unloaded or loaded CMJ were unclear over the 18-week
period. Drop jump performance improved throughout the investigation period with
moderate positive changes in reactive strength index observed (35%; ES 0.97 +/-
0.69). The adaptation response to a structured resistance training program does
not occur linearly in young female athletes. Caution should be taken if assessing
jump height only, as this will provide a biased observation to a training
response. Frequently assessing CMJ performance can aid program design coaching
decisions to ensure improvements are seen past the initial neuromuscular learning
phase in performance training.
PMID- 26439782
TI - The Impact of Back Squat and Leg-Press Exercises on Maximal Strength and Speed
Strength Parameters.
AB - Strength training-induced increases in speed strength seem indisputable. For
trainers and athletes, the most efficient exercise selection in the phase of
preparation is of interest. Therefore, this study determined how the selection of
training exercise influences the development of speed strength and maximal
strength during an 8-week training intervention. Seventy-eight students
participated in this study (39 in the training group and 39 as controls). Both
groups were divided into 2 subgroups. The first training group (squat training
group [SQ]) completed an 8-week strength training protocol using the parallel
squat. The second training group (leg-press training group [LP]) used the same
training protocol using the leg press (45 degrees leg press). The control group
was divided in 2 subgroups as controls for the SQ or the LP. Two-factorial
analyses of variance were performed using a repeated measures model for all group
comparisons and comparisons between pretest and posttest results. The SQ
exhibited a statistically significant (p <= 0.05) increase in jump performance in
squat jump (SJ, 12.4%) and countermovement jump (CMJ, 12.0%). Whereas, the
changes in the LP did not reach statistical significance and amounted to
improvements in SJ of 3.5% and CMJ 0.5%. The differences between groups were
statistically significant (p <= 0.05). There are also indications that the squat
exercise is more effective to increase drop jump performance. Therefore, the
squat exercise increased the performance in SJ, CMJ, and reactive strength index
more effectively compared with the leg-press in a short-term intervention.
Consequently, if the strength training aims at improving jump performance, the
squat should be preferred because of the better transfer effects.
PMID- 26439783
TI - Basketball Performance Is Related to Maturity and Relative Age in Elite
Adolescent Players.
AB - During a national championship, the anthropometric, physiological, and maturation
characteristics of 13- to 14-year-old players of elite basketball teams and their
association with sport performance were analyzed. Body parameters (weight,
height, skinfold thicknesses, and lengths) were measured and physiological
capacities assessed by sprint (20 m) and jump tests (i.e., countermovement jump
with arm swing). Chronological age (CA) and maturity offset (years from age at
peak height velocity; YAPHV) were calculated, and then predicted age at peak
height velocity, as the difference between CA and YAPHV. Game performance was
assessed with point averages and the performance index rating (PIR). The birth
date distribution of players was biased, those born early in the selection year
outnumbering those born later. Anthropometric analysis indicated that players who
performed better had longer body lengths. Physiological testing showed that semi
finalists had better sprint performance than quarter-finalists and those players
with greater jump capacity scored more points. Early maturation and advanced
maturity status were also associated with better PIR and scored points per game.
Multiple blockwise regression analysis showed that, among the factors analyzed,
YAPHV was the best predictor of basketball performance. In conclusion, around
puberty, physical and physiological parameters associated with maturity and CA
are important in determining the success of elite basketball players.
Consequently, boys who are born in the second half of the year and/or late
maturing tend to be marginalized or totally excluded, and not given the chance to
play under equal conditions; their careers may then be held back by the relative
disadvantage associated with inexperience.
PMID- 26439784
TI - Physical Qualities of International Female Rugby League Players by Playing
Position.
AB - The purpose of this study was to investigate the anthropometric, body
composition, and fitness characteristics of female rugby league players by
playing position. Data were collected on 27 players who were part of the English
elite women's rugby league squad. Player assessments comprised anthropometric
(stature and body mass), body composition (dual-energy X-ray absorptiometry) and
fitness {lower-body power (countermovement jump [CMJ], 20 kg jump squat [JS], and
30 cm drop jump), 5, 10, 20, 30, and 40 m sprint, 505 agility, Yo-Yo intermittent
recovery test level 1} measures. Players were classified into playing position
(i.e., forwards and backs) before analysis. A multivariate analysis of variance
demonstrated significant (p <= 0.05) differences for body mass, stature, total
fat, lean mass, and percentage body fat between forwards and backs. Positional
differences were also observed for speed, agility, and lower-body power.
Significant relationships were observed between total body fat and all fitness
variables, and total lean mass was related to CMJ and JS peak power. This study
provides comparative data for female rugby league forwards and backs. Body fat
was strongly associated with performance and should therefore be considered in
developing fitness characteristics. The relationship to match performance and
trainability of these characteristics warrants further investigation.
PMID- 26439785
TI - Effects of Coffee and Caffeine Anhydrous Intake During Creatine Loading.
AB - The purpose of this study was to determine the effect of 5 days of creatine (CRE)
loading alone or in combination with caffeine anhydrous (CAF) or coffee (COF) on
upper-body and lower-body strength and sprint performance. Physically active
males (n = 54; mean +/- SD; age = 20.1 +/- 2.1 years; weight = 78.8 +/- 8.8 kg)
completed baseline testing, consisting of 1 repetition maximum (1RM) and
repetitions to fatigue with 80% 1RM for bench press and leg press, followed by a
repeated sprint test of five, 10-second sprints separated by 60-second rest on a
cycle ergometer to determine peak power (PP) and total power (TP). At least 72
hours later, subjects were randomly assigned to supplement with CRE (5 g of CRE
monohydrate, 4 times per day; n = 14), CRE + CAF (CRE +300 mg.d of CAF; n = 13),
CRE + COF (CRE +8.9 g of COF, yielding 303 mg of CAF; n = 13), or placebo (PLA; n
= 14) for 5 days. Serum creatinine (CRN) was measured before and after
supplementation, and on day 6, participants repeated pretesting procedures.
Strength measures were improved in all groups (p <= 0.05), with no significant
time * treatment interactions. No significant interaction or main effects were
observed for PP. For TP, a time * sprint interaction was observed (p <= 0.05),
with no significant interactions among treatment groups. A time * treatment
interaction was observed for serum CRN values (p <= 0.05) that showed increases
in all groups except PLA. Four subjects reported mild gastrointestinal discomfort
with CRE + CAF, with no side effects reported in other groups. These findings
suggest that neither CRE alone nor in combination with CAF or COF significantly
affected performance compared with PLA.
PMID- 26439786
TI - The Acute Potentiating Effects of Heavy Sled Pulls on Sprint Performance.
AB - This study examined the acute potentiating effects of heavy sprint-style sled
pulls on sprint performance. Twenty-two experienced resistance-trained rugby
athletes performed 2 heavy sprint-style sled pull training protocols on separate
occasions using a randomized, crossover, and counterbalanced design. The
protocols consisted of 2-baseline 15 m sprints followed by 15 m sprints at 4, 8,
and 12 minutes after completing 15 and 7.5 m heavy sled pulls with loads of 75
and 150% body mass (respectively). A significantly faster (p <= 0.05) 15 m sprint
time was observed at 12 minutes for the 75% body mass load. Small nonsignificant
improvements (effect size [ES] = 0.22-0.33) in 5, 10, and 15 m sprint times were
observed at 8 and 12 minutes after the 75% body mass sled pull. No significant
changes were observed for any sprint time after the 150% body mass sled pull.
Significant differences in the percentage of change in sprint times between the 2
sled pull conditions were observed at 4 (ES = 0.44-0.52), 8 (ES = 0.59), and 12
minutes (ES = 0.64). It would seem that the 75% body mass sled pull can be an
effective preload stimulus for improving subsequent sprint performance provided
that adequate recovery (8-12 minutes) is allowed. Practitioners should be advised
that prescription of training load based on decrement in sprint velocity may be
the best approach to determine loading for athletes.
PMID- 26439787
TI - Reactive Strength Index Modified Is a Valid Measure of Explosiveness in
Collegiate Female Volleyball Players.
AB - The purpose of this study was to investigate the validity of the reactive
strength index modified (RSImod) as a measure of lower body explosiveness.
Fifteen female, National Collegiate Athletic Association Division I volleyball
players performed vertical countermovement jumps (CMJs) while standing on a force
plate. Each player performed 3 CMJs. The vertical ground reaction forces
collected during each jump were used to calculate jump height, time to take-off,
time to peak force, peak force, peak rate of force development, and peak power;
the latter 3 variables were all normalized to body mass. Reactive strength index
modified was calculated as the ratio between jump height and time to take-off.
All variables, except for jump height, were then entered a factor analysis, which
reduced the input data into 2 factors: a force factor and a speed factor.
Although RSImod loaded more strongly onto the force factor, further analysis
showed that RSImod loaded positively onto both force and speed factors. Visual
analysis of the Cartesian coordinates also showed that RSImod loaded into the
quadrant of greater force and speed abilities. These results indicate that the
construct of RSImod, as derived from CMJ force-time data, captures a combination
of speed-force factors that can be interpreted as lower body explosiveness during
the CMJ. Reactive strength index modified therefore seems to be a valid measure
to study lower body explosiveness.
PMID- 26439788
TI - Sport-Specific Conditioning Variables Predict Offensive and Defensive Performance
in High-Level Youth Water Polo Athletes.
AB - Specific-conditioning capacities (SCC) are known to be generally important in
water polo (WP), yet the independent associations to offensive and defensive
performance is unknown. This study aimed to determine whether offense and defense
abilities in WP were independently associated with SCC and anthropometrics. The
participants were 82 high-level male youth WP players (all 17-19 years of age;
body height, 186.3 +/- 6.07 cm; body mass, 84.8 +/- 9.6 kg). The independent
variables were body height and body mass, and 5 sport-specific fitness tests:
sprint swimming over 15 meters; 4 * 50-meter anaerobic-endurance test; vertical
in-water-jump; maximum intensity isometric force in upright swimming using an
eggbeater kick; and test of throwing velocity. The 6 dependent variables
comprised parameters of defensive and offensive performance, such as polyvalence,
i.e., ability to play on different positions in defensive tasks (PD) and
offensive tasks (PO), efficacy in primary playing position in defensive (ED) and
offensive (EO) tasks, and agility in defensive (AD) and offensive (AO) tasks.
Analyses showed appropriate reliability for independent (intraclass coefficient
of 0.82-0.91) and dependent variables (Cronbach alpha of 0.81-0.95). Multiple
regressions were significant for ED (R = 0.25; p < 0.01), EO (R = 0.21; p <
0.01), AD (R = 0.40; p < 0.01), and AO (R = 0.35; p < 0.01). Anaerobic-swimming
performance was positively related to AD (beta = -0.26; p <= 0.05), whereas
advanced sprint swimming was related to better AO (beta = -0.38; p <= 0.05). In
water-jumping performance held the significant positive relationship to EO (beta
= 0.31; p <= 0.05), ED (beta = 0.33; p <= 0.05), and AD (beta = 0.37; p <= 0.05).
Strength and conditioning professionals working in WP should be aware of
established importance of SCC in performing unique duties in WP. The SCC should
be specifically developed to meet the needs of offensive and defensive
performance in young WP athletes.
PMID- 26439789
TI - The Effects of Breakdown Set Resistance Training on Muscular Performance and Body
Composition in Young Men and Women.
AB - Breakdown (BD) training has been advocated by multiple commercial and academic
publications and authors, seemingly as a result of the acute hormonal and muscle
activation responses it produces. However, there is a relative dearth of research
that has empirically considered this advanced method of resistance training (RT)
over a chronic intervention while appropriately controlling other RT variables.
The present study considered 36 male and female participants divided into 3
groups: BD (n = 11), heavy-load breakdown (n = 14), and traditional (n = 11),
performing full-body RT programs 2 times per week for 12 weeks. No significant
between-group differences were identified for change in absolute muscular
endurance for chest press, leg press, or pull-down exercises or for body
composition changes. Effect sizes for absolute muscular endurance changes were
large for all groups and exercises (0.86-2.74). The present study supports
previous research that the use of advanced training techniques stimulates no
greater muscular adaptations when compared with performing more simplified RT
protocols to momentary muscular failure.
PMID- 26439790
TI - A Comparison of the Effect of Kettlebell Swings and Isolated Lumbar Extension
Training on Acute Torque Production of the Lumbar Extensors.
AB - The aim of this study was to use a fatigue response test to measure the muscular
fatigue (defined as a reduction in torque production) sustained by the lumbar
extensors after a single set of kettlebell swings (KBS) in comparison with
isolated lumbar extensions (ILEX) and a control condition (CON). The purpose of
which is to measure the physiological response of KBS against an already
established modality. Subsequent data provide insight of the efficacy of
kettlebells swings in strengthening the lumbar muscles and lower back pain
treatment. Eight physically active males participated in a repeated measures
design where participants completed all conditions. There were statistically
significant reductions in maximal torque, reported as strength index (SI), after
both KBS and ILEX exercise. A statistically significant difference was found for
reductions in maximal torque between CON and both KBS (p = 0.005) and ILEX (p =
0.001) and between KBS and ILEX (p = 0.039). Mean reduction and effect sizes were
-1824 +/- 1127.12 (SI) and -1.62 for KBS and -4775.6 +/- 1593.41 (SI) and -3.00
for ILEX. In addition, a statistically significant difference was found between
KBS and ILEX for rate of perceived exertion (p = 0.012). Data suggest that both
KBS and ILEX were able to fatigue the lumbar extensors. Isolated lumbar extension
was able to generate a greater level of fatigue. However, contrary to previous
research, the KBS was able to elicit a physiological response, despite the lack
of pelvic restraint supporting the potential to strengthen the lumbar extensors.
PMID- 26439791
TI - Avirulence gene mapping in the Hessian fly (Mayetiola destructor) reveals a
protein phosphatase 2C effector gene family.
AB - The genetic tractability of the Hessian fly (HF, Mayetiola destructor) provides
an opportunity to investigate the mechanisms insects use to induce plant gall
formation. Here we demonstrate that capacity using the newly sequenced HF genome
by identifying the gene (vH24) that elicits effector-triggered immunity in wheat
(Triticum spp.) seedlings carrying HF resistance gene H24. vH24 was mapped within
a 230-kb genomic fragment near the telomere of HF chromosome X1. That fragment
contains only 21 putative genes. The best candidate vH24 gene in this region
encodes a protein containing a secretion signal and a type-2 serine/threonine
protein phosphatase (PP2C) domain. This gene has an H24-virulence associated
insertion in its promoter that appears to silence transcription of the gene in
H24-virulent larvae. Candidate vH24 is a member of a small family of genes that
encode secretion signals and PP2C domains. It belongs to the fraction of genes in
the HF genome previously predicted to encode effector proteins. Because PP2C
proteins are not normally secreted, our results suggest that these are PP2C
effectors that HF larvae inject into wheat cells to redirect, or interfere, with
wheat signal transduction pathways.
PMID- 26439793
TI - Association of food consumption with total volumes of visceral and subcutaneous
abdominal adipose tissue in a Northern German population.
AB - Excess accumulation of visceral adipose tissue (VAT) is a known risk factor for
cardiometabolic diseases; further, subcutaneous abdominal adipose tissue (SAAT)
and the ratio of both (VAT:SAAT ratio) have been discussed as potentially
detrimental. Information about the association between diet and adipose tissue is
scarce. This study aimed to identify food group intake associated with VAT and
SAAT and the VAT:SAAT ratio in a Northern German population. A cross-sectional
analysis was conducted in 344 men and 241 women who underwent an MRI to quantify
total volumes of VAT and SAAT. Intake of fourteen food groups was assessed with a
self-administered 112-item FFQ. Linear regression models adjusted for age, sex,
energy intake, physical activity, intake of other food groups and mutual
adjustment for VAT and SAAT were calculated to analyse the associations between
standardised food group intake and VAT and SAAT, or the VAT:SAAT ratio. Intakes
of potatoes (P=0.043) and cakes (P=0.003) were positively and inversely,
respectively, associated with both VAT and SAAT. By contrast, intake of cereals
was negatively associated with VAT (P=0.045) only, whereas intakes of eggs
(P=0.006) and non-alcoholic beverages (P=0.042) were positively associated with
SAAT only. The association between eggs and non-alcoholic beverages with SAAT
remained significant after further consideration of VAT. Intake of non-alcoholic
beverages was also inversely associated with the VAT:SAAT ratio (P=0.001). Our
analysis adds to the evidence that intake of foods is independently associated
with VAT or SAAT volumes.
PMID- 26439794
TI - Membrane glycoproteomics of fetal lung fibroblasts using LC/MS.
AB - Some aberrant N-glycosylations are being used as tumor markers, and
glycoproteomics is expected to provide novel diagnosis markers and targets of
drug developments. However, one has trouble in mass spectrometric glycoproteomics
of membrane fraction because of lower intensity of glycopeptides in the existence
of surfactants. Previously, we developed a glycopeptide enrichment method by
acetone precipitation, and it was successfully applied to human serum
glycoproteomics. In this study, we confirmed that this method is useful to remove
the surfactants and applicable to membrane glycoproteomics. The glycoproteomic
approach to the human fetal lung fibroblasts membrane fraction resulted in the
identification of over 272 glycoforms on 63 sites of the 44 glycoproteins.
According to the existing databases, the structural features on 41 sites are
previously unreported. The most frequently occurring forms at N-glycosylation
site were high-mannose type containing nine mannose residues (M9) and monosialo
fucosylated biantennary oligosaccharides. Several unexpected N-glycans, such as
fucosylated complex-type and fucosylated high-mannose and/or fucosylated pauci
mannose types were found in ER and lysosome proteins. Our method provides new
insights into transport, biosynthesis, and degradation of glycoproteins.
PMID- 26439796
TI - RNA-based regulation of transposon expression.
AB - Throughout the domains of life, transposon activity represents a serious threat
to genome integrity and evolution has realized different molecular mechanisms
that aim to inhibit the transposition of mobile DNA. Small noncoding RNAs that
function as guides for Argonaute effector proteins represent a key feature of so
called RNA interference (RNAi) pathways and specialized RNAi pathways exist to
repress transposon activity on the transcriptional and posttranscriptional level.
Transposon transcription can be diminished by targeted DNA methylation or
chromatin remodeling via repressive Histone modifications. Posttranscriptional
transposon silencing bases on degradation of transposon transcripts to prevent
either reverse transcription followed by genomic reintegration or translation
into proteins that mediate the transposition process. In plants, Argonaute-like
proteins guided by short interfering RNAs (siRNAs) are essential for transposon
repression on the epigenetic and posttranscriptional level. In the germline of
animals, these tasks are often assumed by a second subclass of Argonaute proteins
referred to as Piwi-like proteins, which bind a distinct class of small noncoding
RNAs named piwi-interacting RNAs (piRNAs). Though the principals of RNAi pathways
are essentially the same in all eukaryotic organisms, remarkable differences can
be observed even in closely related species reflecting the astonishing plasticity
and diversity of these pathways.
PMID- 26439795
TI - Esculetin induces apoptosis in human colon cancer cells by inducing endoplasmic
reticulum stress.
AB - Colorectal cancer has become more common in many regions of the world. Recently,
we showed that esculetin, a natural coumarin, induces apoptosis in HT-29 colon
cancer cells via the reactive oxygen species-mediated mitochondrial pathway. The
present study examined whether esculetin induces apoptosis in HT-29 colon cancer
cells by inducing endoplasmic reticulum (ER) stress. We found that esculetin
induced characteristic signs of ER stress, confirmed by ER staining,
mitochondrial calcium overload and expression of ER stress-related proteins (i.e.
glucose regulated protein 78, phosphorylated ribonucleic acid-dependent protein
kinase-like ER kinase, phosphorylated inositol requiring enzyme 1, phosphorylated
eukaryotic initiation factor-2alpha, spliced X-box binding protein 1 and cleaved
activating transcription factor 6). Esculetin also induced the expression of the
CCAAT/enhancer-binding protein-homologous protein (CHOP) and pro-apoptotic
factors caspase-12. Moreover, transfection of colon cancer cells with a small
interfering ribonucleic acid targeting CHOP attenuated esculetin-induced
apoptosis. Taken together, these results suggest that the ER stress response
plays an important role in esculetin-induced apoptosis in human colon cancer
cells.
PMID- 26439798
TI - Secukinumab distributes into dermal interstitial fluid of psoriasis patients as
demonstrated by open flow microperfusion.
PMID- 26439797
TI - Sequential therapy with cyclophosphamide and mycophenolic acid in patients with
progressive immunoglobulin A nephropathy: a long-term follow-up.
AB - In progressive immunoglobulin (Ig)A nephropathy (IgAN), cyclophosphamide pulse
therapy (CyP), high-dose intravenous immunoglobulins (IVIg) and mycophenolic acid
(MPA) have been used to stop progressive loss of renal function, but disease
progression may occur after the end of the initial treatment. Here, we report the
long-term follow-up of patients with progressive IgAN with MPA as maintenance
therapy after CyP (CyP-MPA). In a median observation time of 6.2 years, we
analysed the slopes of the loss of renal function of 47 patients with biopsy
proven IgAN and treated with CyP. Thirty-one patients with further progression
were treated with MPA maintenance for a median time of 5.2 years. Follow-up was
compared with symptomatic therapy and IVIg as historically matched control
groups. Median loss of renal function was reduced significantly from 0.9 ml/min
to 0.1 ml/min per month with CyP (P < 0.05), and with MPA in patients with a
relapse from -0.4 ml/min to -0.1 ml/min per month (P < 0.05) until the end of the
study. Proteinuria decreased significantly from 1.6 g/l to 1.0 g/l after CyP, and
during MPA treatment to 0.6 g/l (P = 0.001 Friedman test). Median renal survival
time was in patients with CyP 10.5 years (range = 3.2-17.8), with CyP-MPA 10.7
years (range = 8.3-13.1), with IVIg 4.7 years (range = 2.6-6.6), and in untreated
patients 1.2 years (range = 0.8-1.6; log-rank test P < 0.01). In patients with
progressive IgAN, our long-term follow-up observation indicates that sequential
CyP-MPA therapy maintains renal survival significantly.
PMID- 26439799
TI - Role of mitochondrial calcium uptake homeostasis in resting state fMRI brain
networks.
AB - Mitochondrial Ca(2+) uptake influences both brain energy metabolism and neural
signaling. Given that brain mitochondrial organelles are distributed in relation
to vascular density, which varies considerably across brain regions, we
hypothesized different physiological impacts of mitochondrial Ca(2+) uptake
across brain regions. We tested the hypothesis by monitoring brain "intrinsic
activity" derived from the resting state functional MRI (fMRI) blood oxygen level
dependent (BOLD) fluctuations in different functional networks spanning the
somatosensory cortex, caudate putamen, hippocampus and thalamus, in normal and
perturbed mitochondrial Ca(2+) uptake states. In anesthetized rats at 11.7 T,
mitochondrial Ca(2+) uptake was inhibited or enhanced respectively by treatments
with Ru360 or kaempferol. Surprisingly, mitochondrial Ca(2+) uptake inhibition by
Ru360 and enhancement by kaempferol led to similar dose-dependent decreases in
brain-wide intrinsic activities in both the frequency domain (spectral amplitude)
and temporal domain (resting state functional connectivity; RSFC). The fact that
there were similar dose-dependent decreases in the frequency and temporal domains
of the resting state fMRI-BOLD fluctuations during mitochondrial Ca(2+) uptake
inhibition or enhancement indicated that mitochondrial Ca(2+) uptake and its
homeostasis may strongly influence the brain's functional organization at rest.
Interestingly, the resting state fMRI-derived intrinsic activities in the caudate
putamen and thalamic regions saturated much faster with increasing dosage of
either drug treatment than the drug-induced trends observed in cortical and
hippocampal regions. Regional differences in how the spectral amplitude and RSFC
changed with treatment indicate distinct mitochondrion-mediated spontaneous
neuronal activity coupling within the various RSFC networks determined by resting
state fMRI.
PMID- 26439800
TI - Sustained Epigenetic Drug Delivery Depletes Cholesterol-Sphingomyelin Rafts from
Resistant Breast Cancer Cells, Influencing Biophysical Characteristics of
Membrane Lipids.
AB - Cell-membrane lipid composition can greatly influence biophysical properties of
cell membranes, affecting various cellular functions. We previously showed that
lipid synthesis becomes altered in the membranes of resistant breast cancer cells
(MCF-7/ADR); they form a more rigid, hydrophobic lipid monolayer than do
sensitive cell membranes (MCF-7). These changes in membrane lipids of resistant
cells, attributed to epigenetic aberration, significantly affected drug transport
and endocytic function, thus impacting the efficacy of anticancer drugs. The
present study's objective was to determine the effects of the epigenetic drug, 5
aza-2'-deoxycytidine (DAC), delivered in sustained-release nanogels (DAC-NGs), on
the composition and biophysical properties of membrane lipids of resistant cells.
Resistant and sensitive cells were treated with DAC in solution (DAC-sol) or DAC
NGs, and cell-membrane lipids were isolated and analyzed for lipid composition
and biophysical properties. In resistant cells, we found increased formation of
cholesterol-sphingomyelin (CHOL-SM) rafts with culturing time, whereas DAC
treatment reduced their formation. In general, the effect of DAC-NGs was greater
in changing the lipid composition than with DAC-sol. DAC treatment also caused a
rise in levels of certain phospholipids and neutral lipids known to increase
membrane fluidity, while reducing the levels of certain lipids known to increase
membrane rigidity. Isotherm data showed increased lipid membrane fluidity
following DAC treatment, attributed to decrease levels of CHOL-SM rafts (lamellar
beta [Lbeta] structures or ordered gel) and a corresponding increase in lipids
that form lamellar alpha-structures (Lalpha, liquid crystalline phase). Sensitive
cells showed marginal or insignificant changes in lipid profile following DAC
treatment, suggesting that epigenetic changes affecting lipid biosynthesis are
more specific to resistant cells. Since membrane fluidity plays a major role in
drug transport and endocytic function, treatment of resistant cells with
epigenetic drugs with altered lipid profile could facilitate anticancer drug
transport to overcome acquired drug resistance in a combination therapy.
PMID- 26439801
TI - Hydrogen peroxide mediates hyperglycemia-induced invasive activity via ERK and
p38 MAPK in human pancreatic cancer.
AB - Diabetes mellitus and pancreatic cancer are intimately related, as approximately
85% of pancreatic cancer patients suffer from glucose intolerance or even
diabetes. In this study, we evaluate the underlying mechanism by which
hyperglycemia modulates the invasive potential of cancer cells and contributes to
their enhanced metastatic behavior. Here we show that hyperglycemia increases the
hydrogen peroxide (H2O2) concentration through up-regulation of manganese
superoxide dismutase (SOD2) expression, which further activates the ERK and p38
MAPK pathways, as well as the transcription factors NF-kappaB and AP-1, in a time
dependent manner. The invasion of pancreatic cancer cells resulting from the
activation of the H2O2/MAPK axis under high glucose conditions is effectively
inhibited by PD 98059 (ERK inhibitor), SB 203580 (p38 MAPK inhibitor),
polyethylene glycol-conjugated catalase (PEG-CAT), or the siRNA specific to SOD2.
In addition, streptozotocin-treated diabetic nude mice exhibit a stronger tumor
invasive ability in renal capsule xenografts which could be suppressed by PEG-CAT
treatment. Furthermore, the integrated optical density (IOD) of SOD2 and uPA
stainings is higher in the tumor tissues of pancreatic cancer patients with
diabetes compared with pancreatic cancer patients with euglycemia. Taken
together, our results demonstrate that hyperglycemia enhances cell invasive
ability through the SOD2/H2O2/MAPK axis in human pancreatic cancer. Thus,
SOD2/H2O2/MAPK axis may represent a promising therapeutic target for pancreatic
cancer patients combined with diabetes mellitus.
PMID- 26439802
TI - Down-regulation of the Lamin A/C in neuroblastoma triggers the expansion of tumor
initiating cells.
AB - Tumor-initiating cells constitute a population within a tumor mass that shares
properties with normal stem cells and is considered responsible for therapy
failure in many cancers. We have previously demonstrated that knockdown of the
nuclear envelope component Lamin A/C in human neuroblastoma cells inhibits
retinoic acid-mediated differentiation and results in a more aggressive
phenotype. In addition, Lamin A/C is often lost in advanced tumors and changes in
the nuclear envelope composition occur during tumor progression. Based on our
previous data and considering that Lamin A/C is expressed in differentiated
tissues, we hypothesize that the lack of Lamin A/C could predispose cells toward
a stem-like phenotype, thus influencing the development of tumor-initiating cells
in neuroblastoma. This paper demonstrates that knockdown of Lamin A/C triggers
the development of a tumor-initiating cell population with self-renewing features
in human neuroblastoma cells. We also demonstrates that the development of TICs
is due to an increased expression of MYCN gene and that in neuroblastoma exists
an inverse relationship between LMNA and MYCN expression.
PMID- 26439803
TI - Low EGFR/MET ratio is associated with resistance to EGFR inhibitors in non-small
cell lung cancer.
AB - PURPOSE: Although activating mutations in the epidermal growth factor receptor
(EGFR) gene are predictive markers for response to EGFR inhibitors, 30-40% of
EGFR-mutant non-small cell lung cancer (NSCLC) patients are de novo non
responders. Hence, we sought to explore additional biomarkers of response.
METHODS: We conducted a prospective pilot study to characterize the expression
and/or activation of key receptor tyrosine kinases (RTKs) in stage IIIB-IV NSCLC
tumors. A total of 37 patients were enrolled and 34 underwent EGFR inhibitor
treatment. RESULTS: As expected, patients bearing activating EGFR mutations
showed increased progression free survival (PFS) compared to patients with wild
type EGFR status (9.3 vs 1.4 months, p = 0.0629). Analysis of baseline tumor RTK
profiles revealed that, regardless of EGFR mutation status, higher levels of EGFR
relative to MET correlated with longer PFS. At multiple EGFR/MET ratio cut-offs,
including 1, 2 and 3, median PFS according to below vs. above cut-offs were 0.4
vs. 6.1 (p = 0.0001), 0.5 vs. 9.3 (p = 0.0006) and 1.0 vs. 11.2 months (p =
0.0008), respectively. CONCLUSION: The EGFR/MET ratio measured in tumors at
baseline may help identify NSCLC patients most likely to benefit from prolonged
PFS when treated with EGFR inhibitors.
PMID- 26439805
TI - Targeting the Wnt signaling pathway in colorectal cancer.
AB - INTRODUCTION: The treatment of patients with advanced colorectal cancer still
remains challenging, and identification of new target molecules and therapeutic
avenues remains a priority. The great majority of colorectal cancers have
mutations in one of two genes involved in the Wnt signaling pathway: the
adenomatous polyposis coli (APC) and beta-catenin (CTNNB1) genes. Up to now,
however, no therapeutics for targeting this pathway have been established. AREAS
COVERED: This review article begins with a brief summary of Wnt signaling from
the viewpoints of genetics, cancer stem cell biology, and drug development. We
then overview current attempts to develop drugs directed at various components of
the Wnt signaling pathway. EXPERT OPINION: APC is a tumor suppressor, and
therefore only downstream signal transducers of the APC protein can be considered
as targets for pharmaceutical intervention. TRAF2 and NCK-interacting protein
kinase (TNIK) was identified as the most downstream regulator of Wnt signaling by
two independent research groups, and several classes of small-molecule inhibitors
targeting this protein kinase have been developed. TNIK is a multifunctional
protein with actions that extend beyond Wnt signaling regulation. Such TNIK
inhibitors are expected to have a large variety of clinical applications.
PMID- 26439804
TI - Inhibition of glutamine metabolism counteracts pancreatic cancer stem cell
features and sensitizes cells to radiotherapy.
AB - Pancreatic ductal adenocarcinoma (PDAC) cells utilize a novel non-canonical
pathway of glutamine metabolism that is essential for tumor growth and redox
balance. Inhibition of this metabolic pathway in PDAC can potentially synergize
with therapies that increase intracellular reactive oxygen species (ROS) such as
radiation. Here, we evaluated the dependence of pancreatic cancer stem cells
(PCSCs) on this non-canonical glutamine metabolism pathway and researched whether
inhibiting this pathway can enhance radiosensitivity of PCSCs. We showed that
glutamine deprivation significantly inhibited self-renewal, decreased expression
of stemness-related genes, increased intracellular ROS, and induced apoptosis in
PCSCs. These effects were countered by oxaloacetate, but not alpha-ketoglutarate.
Knockdown of glutamic-oxaloacetic transaminase dramatically impaired PCSCs
properties, while glutamate dehydrogenase knockdown had a limited effect,
suggesting a dependence of PCSCs on non-canonical glutamine metabolism.
Additionally, glutamine deprivation significantly increased radiation-induced ROS
and sensitized PCSCs to fractionated radiation. Moreover, transaminase inhibitors
effectively enhanced ROS generation, promoted radiation sensitivity, and
attenuated tumor growth in nude mice following radiation exposure. Our findings
reveal that inhibiting the non-canonical pathway of glutamine metabolism enhances
the PCSC radiosensitivity and may be an effective adjunct in cancer radiotherapy.
PMID- 26439806
TI - Peptide pi-Electron Conjugates: Organic Electronics for Biology?
AB - Highly ordered arrays of pi-conjugated molecules are often viewed as a
prerequisite for effective charge-transporting materials. Studies involving these
materials have traditionally focused on organic electronic devices, with more
recent emphasis on biological systems. In order to facilitate the transition to
biological environments, biomolecules that can promote hierarchical ordering and
water solubility are often covalently appended to the pi-electron unit. This
review highlights recent work on pi-conjugated systems bound to peptide moieties
that exhibit self-assembly and aims to provide an overview on the development and
emerging applications of peptide-based supramolecular pi-electron systems.
PMID- 26439807
TI - The development of lung biochemical monitoring can play a key role in the early
prediction of bronchopulmonary dysplasia.
AB - AIM: Despite advances in perinatal management, there is a flat trend in
incidences of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia
(BPD) in preterm infants. The main feature of BPD development in preterm infants
is an imbalance between increased exposure to free radicals and inadequate
antioxidant defences. We investigated the associations between BPD and lipid
hydro-peroxide (LOOH) and glutathione (GSH) concentrations in bronchoalveolar
lavage fluid (BALF). METHODS: In this prospective study, BALF samples were
collected from 44 preterm infants with RDS and oxidative stress markers were
measured in 11 with BPD and 33 controls without BPD. RESULTS: LOOH levels were
significantly higher (p < 0.01) in the BPD group (median 16.35; 25th-75th centile
13.75-17.05 nmol/mL) than in the no BPD group (median 13.18; 25th-75th centile
12.92-13.63 nmol/mL). Conversely, GSH levels were significantly lower in the BPD
group (p < 0.01) (median 11.52; 25th-75th centile 6.95-13.85 MUmol/mg) than the
no BPD group (median: 18.69; 25th-75th centile: 13.89-23.64 MUmol/mg). Multiple
regression analysis showed significant correlations between BPD and mechanical
ventilation time (p < 0.01) and LOOH levels (p < 0.05). CONCLUSION: Early LOOH
level increases in preterm infants developing BPD suggest that lung biochemical
monitoring of sick infants might be possible and BPD could be predicted early by
evaluating biomarkers.
PMID- 26439808
TI - Photoactive Self-Shaping Hydrogels as Noncontact 3D Macro/Microscopic
Photoprinting Platforms.
AB - A photocleavable terpolymer hydrogel cross-linked with o-nitrobenzyl derivative
cross-linker is shown to be capable of self-shaping without losing its physical
integrity and robustness due to spontaneous asymmetric swelling of network caused
by UV-light-induced gradient cleavage of chemical cross-linkages. The continuum
model and finite element method are used to elucidate the curling mechanism
underlying. Remarkably, based on the self-changing principle, the photosensitive
hydrogels can be developed as photoprinting soft and wet platforms onto which
specific 3D characters and images are faithfully duplicated in macro/microscale
without contact by UV light irradiation under the cover of customized photomasks.
Importantly, a quick response (QR) code is accurately printed on the photoactive
hydrogel for the first time. Scanning QR code with a smartphone can quickly
connect to a web page. This photoactive hydrogel is promising to be a new
printing or recording material.
PMID- 26439811
TI - Does Staphylococcus aureus have a role in the development of Type 2 diabetes
mellitus?
PMID- 26439810
TI - Studies on Bacterial Proteins Corona Interaction with Saponin Imprinted ZnO
Nanohoneycombs and Their Toxic Responses.
AB - Molecular imprinting generates robust, efficient, and highly mesoporous surfaces
for biointeractions. Mechanistic interfacial interaction between the surface of
core substrate and protein corona is crucial to understand the substantial
microbial toxic responses at a nanoscale. In this study, we have focused on the
mechanistic interactions between synthesized saponin imprinted zinc oxide
nanohoneycombs (SIZnO NHs), average size 80-125 nm, surface area 20.27 m(2)/g,
average pore density 0.23 pore/nm and number-average pore size 3.74 nm and
proteins corona of bacteria. The produced SIZnO NHs as potential antifungal and
antibacterial agents have been studied on Sclerotium rolfsii (S. rolfsii),
Pythium debarynum (P. debarynum) and Escherichia coli (E. coli), Staphylococcus
aureus (S. aureus), respectively. SIZnO NHs exhibited the highest antibacterial
(~50%) and antifungal (~40%) activity against Gram-negative bacteria (E. coli)
and fungus (P. debarynum), respectively at concentration of 0.1 mol. Scanning
electron spectroscopy (SEM) observation showed that the ZnO NHs ruptured the cell
wall of bacteria and internalized into the cell. The molecular docking studies
were carried out using binding proteins present in the gram negative bacteria
(lipopolysaccharide and lipocalin Blc) and gram positive bacteria (Staphylococcal
Protein A, SpA). It was envisaged that the proteins present in the bacterial cell
wall were found to interact and adsorb on the surface of SIZnO NHs thereby
blocking the active sites of the proteins used for cell wall synthesis. The
binding affinity and interaction energies were higher in the case of binding
proteins present in gram negative bacteria as compared to that of gram positive
bacteria. In addition, a kinetic mathematical model (KMM) was developed in MATLAB
to predict the internalization in the bacterial cellular uptake of the ZnO NHs
for better understanding of their controlled toxicity. The results obtained from
KMM exhibited a good agreement with the experimental data. Exploration of
mechanistic interactions, as well as the formation of bioconjugate of proteins
and ZnO NHs would play a key role to interpret more complex biological systems in
nature.
PMID- 26439809
TI - Induced pluripotent stem cells for cardiovascular disease: from product-focused
disease modeling to process-focused disease discovery.
AB - Induced pluripotent stem (iPS) cell technology offers an unprecedented
opportunity to study patient-specific disease. This biotechnology platform
enables recapitulation of individualized disease signatures in a dish through
differentiation of patient-derived iPS cells. Beyond disease modeling, the in
vitro process of differentiation toward genuine patient tissue offers a blueprint
to inform disease etiology and molecular pathogenesis. Here, we highlight recent
advances in patient-specific cardiac disease modeling and outline the future
promise of iPS cell-based disease discovery applications.
PMID- 26439812
TI - Comparison between Free and Immobilized Ion Effects on Hydrophobic Interactions:
A Molecular Dynamics Study.
AB - Fundamental studies of the effect of specific ions on hydrophobic interactions
are driven by the need to understand phenomena such as hydrophobically driven
self-assembly or protein folding. Using beta-peptide-inspired nanorods, we
investigate the effects of both free ions (dissolved salts) and proximally
immobilized ions on hydrophobic interactions. We find that the free ion effect is
correlated with the water density fluctuation near a nonpolar molecular surface,
showing that such fluctuation can be an indicator of hydrophobic interactions in
the case of solution additives. In the case of immobilized ion, our results
demonstrate that hydrophobic interactions can be switched on and off by choosing
different spatial arrangements of proximal ions on a nanorod. For globally
amphiphilic nanorods, we find that the magnitude of the interaction can be
further tuned using proximal ions with varying ionic sizes. In general, univalent
proximal anions are found to weaken hydrophobic interactions. This is in contrast
to the effect of free ions, which according to our simulations strengthen
hydrophobic interactions. In addition, immobilized anions of increasing ionic
size do not follow the same ordering (Hofmeister-like ranking) as free ions when
it comes to their impact on hydrophobic interactions. The immobilized ion effect
is not simply correlated with the water density fluctuation near the nonpolar
side of the amphiphilic nanorod. We propose a molecular picture that explains the
contrasting effects of immobilized versus free ions.
PMID- 26439813
TI - Crystal-Templated Colloidal Clusters Exhibit Directional DNA Interactions.
AB - Spherical colloids covered with grafted DNA have been used in the directed self
assembly of a number of distinct crystal and gel structures. Simulation suggests
that the use of anisotropic building blocks greatly augments the variety of
potential colloidal assemblies that can be formed. Here, we form five distinct
symmetries of colloidal clusters from DNA-functionalized spheres using a single
type of colloidal crystal as a template. The crystals are formed by simple
sedimentation of a binary mixture containing a majority "host" species that forms
close-packed crystals with the minority "impurity" species occupying
substitutional or interstitial defect sites. After the DNA strands between the
two species are hybridized and enzymatically ligated, the results are colloidal
clusters, one for each impurity particle, with a symmetry determined by the
nearest neighbors in the original crystal template. By adjusting the size ratio
of the two spheres and the timing of the ligation, we are able to generate
clusters having the symmetry of tetrahedra, octahedra, cuboctahedra, triangular
orthobicupola, and icosahedra, which can be readily separated from defective
clusters and leftover spheres by centrifugation. We further demonstrate that
these clusters, which are uniformly covered in DNA strands, display directional
binding with spheres bearing complementary DNA strands, acting in a manner
similar to patchy particles or proteins having multiple binding sites. The
scalable nature of the fabrication process, along with the reprogrammability and
directional nature of their resulting DNA interactions, makes these clusters
suitable building blocks for use in further rounds of directed self-assembly.
PMID- 26439814
TI - Lewis Basic Sulfide Catalyzed Electrophilic Bromocyclization of Cyclopropylmethyl
Amide.
AB - A Lewis basic sulfide catalyzed electrophilic bromocyclization of
cyclopropylmethyl amide has been developed. The catalytic protocol is applicable
to both 1,1- and 1,2-substituted cyclopropylmethyl amides, giving oxazolines and
oxazines in good yields and excellent diastereoselectivity.
PMID- 26439815
TI - Factors influencing Chinese college students' preferences for mental health
professionals.
AB - BACKGROUND: Transition from high school to college can be particularly difficult
and stressful for Chinese college students because of parent expectations. AIMS:
The purpose of this study was to examine therapist variables influencing Chinese
college students' preferences for mental health professionals using conjoint
analysis. METHOD: Two hundred fifty-eight community college students in Hong Kong
were asked to rate the profile of 55 mental health professionals representing a
combination of therapist characteristics (i.e., gender, age, race/ethnicity,
professional background, and training institutions) from the most to least
preferred therapist from whom to seek psychological counselling. FINDINGS:
Results indicated that students' preference formation was based largely on
professional background and training institution of the mental health
professionals. Clinical psychologists and clinical social workers were preferred
over educational psychologists (school psychologists), counsellors, and
psychiatrists. Mental health professionals who received training from more
prestigious schools were preferred over those trained at less prestigious
schools. CONCLUSIONS: Understanding clients' preference formation for choosing
mental health professionals could be the first step to gain insights for
developing effective educational and outreach strategies to promote help seeking
behavior and mental health service utilization among Chinese college students.
PMID- 26439816
TI - The effects of metformin treatment of gestational diabetes on maternal weight and
glucose tolerance postpartum--a prospective follow-up study.
AB - INTRODUCTION: Metformin seems to reduce gestational weight gain compared with
insulin in women with gestational diabetes (GDM). Women with GDM requiring
insulin are more likely to develop abnormal glucose tolerance postpartum than
women treated with diet only. In this prospective follow-up study of a randomized
clinical trial, we investigated the effect of metformin treatment in women with
GDM on weight gain and glucose tolerance postpartum. MATERIALS AND METHODS: Women
with GDM with two or more pathologic glucose values at 2-h 75-g oral glucose
tolerance test (OGTT) were recruited. Those needing medication to achieve
sufficient glycemic control were randomized at 22-34 weeks of gestation to either
metformin (n = 110) or insulin (n = 107) treatment until delivery. A third GDM
group (n = 128) requiring no medication had only diet treatment. Weight, OGTT and
glycosylated hemoglobin (HbA1c) were determined at 6-8 weeks and 1 year
postpartum. RESULTS: At least one postpartum visit was attended by 104, 101 and
120 women in the metformin, insulin and diet-only groups, respectively. No
significant differences were found in the change of weight, HbA1c or OGTT glucose
values between the groups during the study (p >= 0.121 in all comparisons). One
year postpartum the diet-only group had less impaired glucose tolerance compared
with the metformin and insulin groups (7.1%, 19.1% and 15.6%, respectively;
overall p = 0.039) and a lower incidence of diabetes (p = 0.027). CONCLUSIONS:
Short-term metformin therapy does not affect weight, HbA1c or OGTT glucose values
postpartum compared with insulin or diet-only treatments. Women with GDM
requiring no medication are least likely to develop impaired glucose tolerance or
diabetes postpartum.
PMID- 26439817
TI - Variability, toxicity, and antioxidant activity of Eupatorium cannabinum (hemp
agrimony) essential oils.
AB - CONTENT: Eupatorium cannabinum L. (Asteraceae) is as a potential source of
biologically active compounds. The plant is used in traditional medicine for the
treatment of diarrhea and livers diseases. OBJECTIVE: The present study provides
investigation on pharmacological properties (antioxidant and toxic activities) of
essential oils of E. cannabinum, collected from 11 wild populations in Lithuania.
MATERIALS AND METHODS: Twenty-two hemp agrimony essential oil samples were
prepared by hydrodistillation according to the European Pharmacopoeia, and their
chemical composition was determined by GC-FID and GC-MS. Compositional data were
subjected to principal components analysis (PCA). Instead of conventional
spectrophotometric methods, cyclic voltammetry (CV) and square wave voltammetry
(SWV) techniques were applied to determine antioxidant activity of hemp agrimony
essential oils. Meanwhile, toxicity of the oils was determined using brine shrimp
(Artemia sp.) assay. RESULTS: Chemical profiles of E. cannabinum oils were
described according to the first predominant components: germacrene D (<=22.0%),
neryl acetate (<=20.0%), spathulenol (<=27.2%), and alpha-terpinene (11.5%). For
the first time, alpha-zingiberene (<=7.8%) was found to be among three major
constituents (as the second one) for hemp agrimony oils. SWV measurements
revealed that oxidation potentials of compounds present in the oils are lower
(below 0.1 V) compared with that of well-known antioxidant quercetin (0.15 V).
Toxicity tests evaluated that hemp agrimony oils containing predominant amounts
of germacrene D and neryl acetate were notably toxic (LC50 value 16.3-22.0
MUg/mL). CONCLUSION: The study provided some new data concerning chemical
composition and pharmaceutical properties of E. cannabinum essential oils.
PMID- 26439820
TI - Married Women's Justification of Intimate Partner Violence in Bangladesh:
Examining Community Norm and Individual-Level Risk Factors.
AB - One-third of the women worldwide experience intimate partner violence (IPV) that
increases their vulnerability to both short- and long-term physical, sexual,
reproductive, and mental health problems. Surprisingly, IPV is justified by many
women globally. Although the IPV literature to date is mostly focused on risk
factors associated with actual occurrences, little is known on attitudinal
acceptance of such violence. Also, despite the growing scholarship of community
influence and health link, IPV research has relatively overlooked the effects of
norms at the community level. Using a representative national sample of 13,611
married women in Bangladesh, this study examined the association of community
attitudes and women's individual attitudes toward wife beating. The results
revealed that women living in communities with permissive attitudes toward wife
beating were more likely to justify husbands' beating (OR=4.5). Women married at
a younger age, who had less than primary-level education, lived in households
categorized as poor or middle class, and did not consume media appeared to be at
higher risk for justifying wife beating. This research adds to a growing research
body on community influences on health by examining IPV attitudes and community
norms link.
PMID- 26439818
TI - Catalytic Olefin Hydroamidation Enabled by Proton-Coupled Electron Transfer.
AB - Here we report a ternary catalyst system for the intramolecular hydroamidation of
unactivated olefins using simple N-aryl amide derivatives. Amide activation in
these reactions occurs via concerted proton-coupled electron transfer (PCET)
mediated by an excited state iridium complex and weak phosphate base to furnish a
reactive amidyl radical that readily adds to pendant alkenes. A series of H-atom,
electron, and proton transfer events with a thiophenol cocatalyst furnish the
product and regenerate the active forms of the photocatalyst and base.
Mechanistic studies indicate that the amide substrate can be selectively
homolyzed via PCET in the presence of the thiophenol, despite a large difference
in bond dissociation free energies between these functional groups.
PMID- 26439821
TI - The Effect of Iron Deficiency on Osmotic Sensitivity of Red Blood Cells from
Neonatal Rats and Their Mothers.
AB - Iron deficiency during pregnancy has many effects on both the mother and her
developing foetus. These can be both short and long term. One effect is an
alteration in fatty acid metabolism and we hypothesised that these changes may
result in alterations in membrane function and structure. In order to test this
hypothesis, we measured osmotic sensitivity in red blood cells isolated from
neonates and their mothers at different times following birth. We fed female rats
control or iron-deficient diets for 4 weeks prior to mating and kept them on the
same diet until term. At that time, we returned one group of deficient dams to
the control diet. The others were kept on the same diet. We showed that iron
deficiency results in a decrease in osmotic sensitivity in the mothers but not in
their neonates. Returning the dams to the control diet resulted in a return of
their red cell osmotic sensitivity to control levels. In the neonates, there was
no recovery in haematocrit or in any other parameter, though they did not get any
worse, in contrast to the pups being suckled by deficient mothers. The data show
two things. The first is that following birth, the mother restores her own iron
stores at the expense of the pups, and secondly, there are differences in
properties and sensitivities between red cells from mothers and their neonates.
This latter observation cannot be explained by differences in the membrane fatty
acid profiles, which were not significantly different.
PMID- 26439822
TI - An expected increase in the efficiency of antiproton cancer therapy with the use
of gold nanoparticles.
AB - The use of gold nanoparticles in antiproton cancer therapy is proposed. The
energy transferred to gold by particles bombarding a tumor and arising in it is
considered as one of the parameters determining the biological effect of gold in
proton and antiproton cancer therapies. An example corresponding to the
assumption about the importance of this parameter is analyzed. It is shown that
the energy transferred to gold by products of annihilation of stopped antiprotons
in soft biological tissues can exceed that transferred by antiprotons before
their annihilation.
PMID- 26439823
TI - On-site semi-automatic calibration and registration of a projector-camera system
using arbitrary objects with known geometry.
AB - In the Shader Lamps concept, a projector-camera system augments physical objects
with projected virtual textures, provided that a precise intrinsic and extrinsic
calibration of the system is available. Calibrating such systems has been an
elaborate and lengthy task in the past and required a special calibration
apparatus. Self-calibration methods in turn are able to estimate calibration
parameters automatically with no effort. However they inherently lack global
scale and are fairly sensitive to input data. We propose a new semi-automatic
calibration approach for projector-camera systems that - unlike existing auto
calibration approaches - additionally recovers the necessary global scale by
projecting on an arbitrary object of known geometry. To this end our method
combines surface registration with bundle adjustment optimization on points
reconstructed from structured light projections to refine a solution that is
computed from the decomposition of the fundamental matrix. In simulations on
virtual data and experiments with real data we demonstrate that our approach
estimates the global scale robustly and is furthermore able to improve
incorrectly guessed intrinsic and extrinsic calibration parameters thus
outperforming comparable metric rectification algorithms.
PMID- 26439824
TI - Radiometric compensation for cooperative distributed multi-projection system
through 2-DOF distributed control.
AB - This paper proposes a novel radiometric compensation technique for cooperative
projection system based-on distributed optimization. To achieve high scalability
and robustness, we assume cooperative projection environments such that 1. each
projector does not have information about other projectors as well as target
images, 2. the camera does not have information about the projectors either,
while having the target images, and 3. only a broadcast communication from the
camera to the projectors is allowed to suppress the data transfer bandwidth. To
this end, we first investigate a distributed optimization based feedback
mechanism that is suitable for the required decentralized information processing
environment. Next, we show that this mechanism works well for still image
projection, however not necessary for moving images due to the lack of dynamic
responsiveness. To overcome this issue, we propose to implement an additional
feedforward mechanism. Such a 2 Degree Of Freedom (2-DOF) control structure is
well-known in control engineering community as a typical method to enhance not
only disturbance rejection but also reference tracking capability,
simultaneously. We theoretically guarantee and experimentally demonstrate that
this 2-DOF structure yields the moving image projection accuracy that is
overwhelming the best achievable performance only by the distributed optimization
mechanisms.
PMID- 26439825
TI - Very high frame rate volumetric integration of depth images on mobile devices.
AB - Volumetric methods provide efficient, flexible and simple ways of integrating
multiple depth images into a full 3D model. They provide dense and photorealistic
3D reconstructions, and parallelised implementations on GPUs achieve real-time
performance on modern graphics hardware. To run such methods on mobile devices,
providing users with freedom of movement and instantaneous reconstruction
feedback, remains challenging however. In this paper we present a range of
modifications to existing volumetric integration methods based on voxel block
hashing, considerably improving their performance and making them applicable to
tablet computer applications. We present (i) optimisations for the basic data
structure, and its allocation and integration; (ii) a highly optimised raycasting
pipeline; and (iii) extensions to the camera tracker to incorporate IMU data. In
total, our system thus achieves frame rates up 47 Hz on a Nvidia Shield Tablet
and 910 Hz on a Nvidia GTX Titan XGPU, or even beyond 1.1 kHz without
visualisation.
PMID- 26439826
TI - MobileFusion: real-time volumetric surface reconstruction and dense tracking on
mobile phones.
AB - We present the first pipeline for real-time volumetric surface reconstruction and
dense 6DoF camera tracking running purely on standard, off-the-shelf mobile
phones. Using only the embedded RGB camera, our system allows users to scan
objects of varying shape, size, and appearance in seconds, with real-time
feedback during the capture process. Unlike existing state of the art methods,
which produce only point-based 3D models on the phone, or require cloud-based
processing, our hybrid GPU/CPU pipeline is unique in that it creates a connected
3D surface model directly on the device at 25Hz. In each frame, we perform dense
6DoF tracking, which continuously registers the RGB input to the incrementally
built 3D model, minimizing a noise aware photoconsistency error metric. This is
followed by efficient key-frame selection, and dense per-frame stereo matching.
These depth maps are fused volumetrically using a method akin to KinectFusion,
producing compelling surface models. For each frame, the implicit surface is
extracted for live user feedback and pose estimation. We demonstrate scans of a
variety of objects, and compare to a Kinect-based baseline, showing on average ~
1.5cm error. We qualitatively compare to a state of the art point-based mobile
phone method, demonstrating an order of magnitude faster scanning times, and
fully connected surface models.
PMID- 26439827
TI - ModulAR: eye-controlled vision augmentations for head mounted displays.
AB - In the last few years, the advancement of head mounted display technology and
optics has opened up many new possibilities for the field of Augmented Reality.
However, many commercial and prototype systems often have a single display
modality, fixed field of view, or inflexible form factor. In this paper, we
introduce Modular Augmented Reality (ModulAR), a hardware and software framework
designed to improve flexibility and hands-free control of video see-through
augmented reality displays and augmentative functionality. To accomplish this
goal, we introduce the use of integrated eye tracking for on-demand control of
vision augmentations such as optical zoom or field of view expansion. Physical
modification of the device's configuration can be accomplished on the fly using
interchangeable camera-lens modules that provide different types of vision
enhancements. We implement and test functionality for several primary
configurations using telescopic and fisheye camera-lens systems, though many
other customizations are possible. We also implement a number of eye-based
interactions in order to engage and control the vision augmentations in real
time, and explore different methods for merging streams of augmented vision into
the user's normal field of view. In a series of experiments, we conduct an in
depth analysis of visual acuity and head and eye movement during search and
recognition tasks. Results show that methods with larger field of view that
utilize binary on/off and gradual zoom mechanisms outperform snapshot and sub
windowed methods and that type of eye engagement has little effect on
performance.
PMID- 26439828
TI - Semi-parametric color reproduction method for optical see-through head-mounted
displays.
AB - The fundamental issues in Augmented Reality (AR) are on how to naturally mediate
the reality with virtual content as seen by users. In AR applications with
Optical See-Through Head-Mounted Displays (OST-HMD), the issues often raise the
problem of rendering color on the OST-HMD consistently to input colors. However,
due to various display constraints and eye properties, it is still a challenging
task to indistinguishably reproduce the colors on OST-HMDs. An approach to solve
this problem is to pre-process the input color so that a user perceives the
output color on the display to be the same as the input. We propose a color
calibration method for OST-HMDs. We start from modeling the physical optics in
the rendering and perception process between the HMD and the eye. We treat the
color distortion as a semi-parametric model which separates the non-linear color
distortion and the linear color shift. We demonstrate that calibrated images
regain their original appearance on two OST-HMD setups with both synthetic and
real datasets. Furthermore, we analyze the limitations of the proposed method and
remaining problems of the color reproduction in OST-HMDs. We then discuss how to
realize more practical color reproduction methods for future HMD-eye system.
PMID- 26439829
TI - Changes in intraocular pressure during surgery in the lateral decubitus position
under sevoflurane and propofol anesthesia.
AB - Intraocular pressure (IOP) has been shown to change with body position. Several
studies have shown that the lateral decubitus position (LDP) is associated with a
significant increase in IOP in the dependent eye. However, whether anesthetic
agents alter IOP in the LDP remains unclear. This study investigated the effect
of sevoflurane and propofol anesthesia on IOP in the LDP. A total of 28 patients
undergoing surgery in the LDP were included. Patients were randomly allocated to
sevoflurane or propofol groups. IOP in both eyes was recorded and compared
between groups at five time points: after anesthesia induction, after
endotracheal intubation, at 5 min and 1 h after a positional change to the LDP,
and 5 min after returning to the supine position. In the sevoflurane group, IOP
was significantly increased in both dependent and non-dependent eyes 1 h after
changing to the LDP. In the propofol group, IOP decreased in both dependent and
non-dependent eyes after tracheal intubation, but did not increase after changing
to the LDP. The number of patients in whom IOP increased to >=28 mmHg was greater
in the sevoflurane group than in the propofol group. Propofol may be better than
sevoflurane for the maintenance of anesthesia in the LDP. Monitoring of IOP in
the LDP might help avoid ophthalmic complications.
PMID- 26439830
TI - Multi-parameter vital sign database to assist in alarm optimization for general
care units.
AB - Continual vital sign assessment on the general care, medical-surgical floor is
expected to provide early indication of patient deterioration and increase the
effectiveness of rapid response teams. However, there is concern that continual,
multi-parameter vital sign monitoring will produce alarm fatigue. The objective
of this study was the development of a methodology to help care teams optimize
alarm settings. An on-body wireless monitoring system was used to continually
assess heart rate, respiratory rate, SpO2 and noninvasive blood pressure in the
general ward of ten hospitals between April 1, 2014 and January 19, 2015. These
data, 94,575 h for 3430 patients are contained in a large database, accessible
with cloud computing tools. Simulation scenarios assessed the total alarm rate as
a function of threshold and annunciation delay (s). The total alarm rate of ten
alarms/patient/day predicted from the cloud-hosted database was the same as the
total alarm rate for a 10 day evaluation (1550 h for 36 patients) in an
independent hospital. Plots of vital sign distributions in the cloud-hosted
database were similar to other large databases published by different authors.
The cloud-hosted database can be used to run simulations for various alarm
thresholds and annunciation delays to predict the total alarm burden experienced
by nursing staff. This methodology might, in the future, be used to help reduce
alarm fatigue without sacrificing the ability to continually monitor all vital
signs.
PMID- 26439831
TI - Sensor fusion methods for reducing false alarms in heart rate monitoring.
AB - Automatic patient monitoring is an essential resource in hospitals for good
health care management. While alarms caused by abnormal physiological conditions
are important for the delivery of fast treatment, they can be also a source of
unnecessary noise because of false alarms caused by electromagnetic interference
or motion artifacts. One significant source of false alarms is related to heart
rate, which is triggered when the heart rhythm of the patient is too fast or too
slow. In this work, the fusion of different physiological sensors is explored in
order to create a robust heart rate estimation. A set of algorithms using heart
rate variability index, Bayesian inference, neural networks, fuzzy logic and
majority voting is proposed to fuse the information from the electrocardiogram,
arterial blood pressure and photoplethysmogram. Three kinds of information are
extracted from each source, namely, heart rate variability, the heart rate
difference between sensors and the spectral analysis of low and high noise of
each sensor. This information is used as input to the algorithms. Twenty
recordings selected from the MIMIC database were used to validate the system. The
results showed that neural networks fusion had the best false alarm reduction of
92.5 %, while the Bayesian technique had a reduction of 84.3 %, fuzzy logic 80.6
%, majority voter 72.5 % and the heart rate variability index 67.5 %. Therefore,
the proposed algorithms showed good performance and could be useful in bedside
monitors.
PMID- 26439819
TI - Protective Effect of Salvia Przewalskii Extract on Puromycin-Induced Podocyte
Injury.
AB - BACKGROUND: To determine the effect of Salvia przewalskii extract (SPE) from
total phenolic acids on puromycin aminonucleoside (PAN)-induced rat podocyte
injury. METHODS: The rats were divided into groups that were treated with either
PAN only or PAN followed by tacrolimus or SPE. We evaluated the effects of SPE on
podocyte injury 5, 10, 15 and 21 days following treatment. RESULTS: (1)
Proteinuria was observed starting on day 5 in all groups. The peak levels of
proteinuria differed among the groups with tacrolimus and high-dose SPE, which
significantly decreased proteinuria relative to the PAN and low- and medium-dose
SPE groups. The proteinuria in each group decreased by day 15 and returned to a
normal level by day 21. (2) H&E and PAS staining revealed no abnormality in
glomerular morphology. With electron microscopy, we observed foot process
effacement in the rats of all groups starting on day 5, but rats in the
tacrolimus and high-dose SPE groups exhibited a lower degree. (3) IHC staining of
nephrin and podocin revealed unaffected expression and better linear
distributions in the high-dose SPE and tacrolimus groups. Western blot analysis
confirmed that SPE could improve the expression of proteins. (4) The mRNA levels
of nephrin and podocin in the tacrolimus and high-dose SPE groups were
significantly higher than that in the others. CONCLUSION: In our study, we first
demonstrated the ability of SPE to reduce proteinuria, preserve the morphology
and structure of podocytes and retain the levels of slit diaphragm proteins on
PAN-induced rat podocytes injury.
PMID- 26439833
TI - Increase in the photoreactivity of uracil derivatives by doubling thionation.
AB - The ability of 4-thiouracil to strongly absorb UVA radiation and to populate a
reactive triplet state in high yield has enabled its use as a versatile
photocrosslinker for nearly 50 years. In this contribution, we present a detailed
spectroscopic and photochemical investigation of the 2-thiouracil, 4-thiouracil,
and 2,4-dithiouracil series in an effort to further advance this chemistry and to
scrutinize the photoreactivity of 2,4-dithiouracil. Our results reveal that
excitation of 2,4-dithiouracil leads to intersystem crossing to the triplet
manifold in 220 +/- 40 fs, which enables the population of the reactive triplet
state with near unity yield (PhiT = 0.90 +/- 0.15) and ultimately leads to a ca.
50% singlet oxygen generation (PhiDelta = 0.49 +/- 0.02)-one of the highest
singlet oxygen yields reported to date for a photoexcited thiobase. In addition,
the long-lived triplet state of 2,4-dithiouracil reacts efficiently with the
nucleic acid base adenine 5'-monophosphate through a direct, oxygen-independent
photocycloaddition mechanism and at a rate that is at least 3-fold faster than
that of 4-thiouracil under equal conditions. The new physico-chemical insights
reported for these RNA-thiobase derivatives are compared to those of the DNA and
RNA bases and the DNA-thiobase derivatives. Furthermore, the strong near-visible
absorption and increased photoreactivity measured for 2,4-dithiouracil lays a
solid foundation for developing RNA-targeted photocrosslinking and
phototherapeutic agents that are more effective than those currently available.
PMID- 26439834
TI - Association between the functional MHC2TA -168 A/G polymorphism and
susceptibility to rheumatoid arthritis: a meta-analysis.
AB - The aim of this study was to determine whether the functional major
histocompatibility complex II transactivator (MHC2TA) -168 A/G polymorphism is
associated with susceptibility to rheumatoid arthritis (RA). A meta-analysis was
conducted to estimate the association between the MHC2TA-168 A/G polymorphism and
RA. A total of 15 comparative studies, which included 14,158 patients and 13,642
controls, were included in the meta-analysis. Based on the meta-analysis, there
was no association between RA and the MHC2TA -168 G allele in the study subjects
(OR = 1.046, 95 % CI = 0.987-1.108, p = 0.130) or Caucasians (OR = 1.027, 95 % CI
= 0.986-1.070, p = 0.193). However, the country-specific meta-analysis revealed
an association between the MHC2TA -168 G allele and RA in the Swedish population
(OR = 1.131, 95 % CI = 1.023-1.250, p = 0.016). A direct comparison between
rheumatoid factor (RF)-positive and RF-negative patients revealed that the
frequency of the G allele was significantly lower in RF-positive patients (OR =
0.783, 95 % CI = 0.628-0.975, p = 0.029) than in RF-negative patients. This meta
analysis demonstrated that the MHC2TA -168 A/G polymorphism is not associated
with susceptibility to RA in Caucasians.
PMID- 26439835
TI - Dynamics of murine B lymphocytes is modulated by in vivo treatment with steroid
ouabain.
AB - Ouabain (OUA) is a steroid hormone capable of inhibiting the protein Na+K+ATPase
present in the plasma membrane of cells. Ouabain was initially extracted from the
roots of African trees such as Acocanthera ouabaio and Strophantus gratus seeds
and later described as an endogenous component found in higher mammals. The
adrenal gland is the main site of synthesis of ouabain and it is released in
stressful situations, conditions similar to those where there is secretion of
corticosteroids. Immunological functions have been shown to be regulated by
ouabain. In order to understand the effects of ouabain on B lymphocyte
populations in different lymphoid organs, mice received intraperitoneal
injections of ouabain for 3 consecutive days. Twenty-four hours after the last
injection, cells were analyzed by flow cytometry. In the spleen, ouabain
modulated especially follicular B cells, inducing a significant decrease in the
percentage and absolute numbers of those cells. Ouabain also reduced the absolute
number of marginal zone B lymphocytes. No difference in the percentage or
absolute number of B lymphocytes in the spleen forty-eight hours after the last
injection was observed. An increase in the number of B cells was seen in
mesenteric lymph nodes and this retention appears to be directly related to
increased expression of CXCR5 chemokine receptor and reduction of CD62L, which
also explains the observed reduction of B cells in the spleen. Our results
indicate that ouabain regulates the dynamics of B lymphocytes in peripheral
organs but production of total IgM and IgG in the serum of animals treated in
vivo with ouabain was not affected.
PMID- 26439832
TI - Reducing tau aggregates with anle138b delays disease progression in a mouse model
of tauopathies.
AB - Pathological tau aggregation leads to filamentous tau inclusions and
characterizes neurodegenerative tauopathies such as Alzheimer's disease and
frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregation
coincides with clinical symptoms and is thought to mediate neurodegeneration.
Transgenic mice overexpressing mutant human P301S tau exhibit many
neuropathological features of human tauopathies including behavioral deficits and
increased mortality. Here, we show that the di-phenyl-pyrazole anle138b binds to
aggregated tau and inhibits tau aggregation in vitro and in vivo. Furthermore,
anle138b treatment effectively ameliorates disease symptoms, increases survival
time and improves cognition of tau transgenic PS19 mice. In addition, we found
decreased synapse and neuron loss accompanied by a decreased gliosis in the
hippocampus. Our results suggest that reducing tau aggregates with anle138b may
represent an effective and promising approach for the treatment of human
tauopathies.
PMID- 26439836
TI - Accurate and Efficient Resolution of Overlapping Isotopic Envelopes in Protein
Tandem Mass Spectra.
AB - It has long been an analytical challenge to accurately and efficiently resolve
extremely dense overlapping isotopic envelopes (OIEs) in protein tandem mass
spectra to confidently identify proteins. Here, we report a computationally
efficient method, called OIE_CARE, to resolve OIEs by calculating the relative
deviation between the ideal and observed experimental abundance. In the OIE_CARE
method, the ideal experimental abundance of a particular overlapping isotopic
peak (OIP) is first calculated for all the OIEs sharing this OIP. The relative
deviation (RD) of the overall observed experimental abundance of this OIP
relative to the summed ideal value is then calculated. The final individual
abundance of the OIP for each OIE is the individual ideal experimental abundance
multiplied by 1 + RD. Initial studies were performed using higher-energy
collisional dissociation tandem mass spectra on myoglobin (with direct infusion)
and the intact E. coli proteome (with liquid chromatographic separation).
Comprehensive data at the protein and proteome levels, high confidence and good
reproducibility were achieved. The resolving method reported here can, in
principle, be extended to resolve any envelope-type overlapping data for which
the corresponding theoretical reference values are available.
PMID- 26439837
TI - Generation of Bioactive Oxylipins from Exogenously Added Arachidonic,
Eicosapentaenoic and Docosahexaenoic Acid in Primary Human Brain Microvessel
Endothelial Cells.
AB - The human blood-brain barrier (BBB) is the restrictive barrier between the brain
parenchyma and the circulating blood and is formed in part by microvessel
endothelial cells. The brain contains significant amounts of arachidonic acid
(ARA), and docosahexaenoic acid (DHA), which potentially give rise to the
generation of bioactive oxylipins. Oxylipins are oxygenated fatty acid
metabolites that are involved in an assortment of biological functions regulating
neurological health and disease. Since it is not known which oxylipins are
generated by human brain microvessel endothelial cells (HBMECs), they were
incubated for up to 30 min in the absence or presence of 0.1-mM ARA,
eicosapentaenoic acid (EPA) or DHA bound to albumin (1:1 molar ratio), and the
oxylipins generated were examined using high performance liquid chromatography
tandem mass spectrometry (HPLC/MS/MS). Of 135 oxylipins screened in the media, 63
were present at >0.1 ng/mL at baseline, and 95 were present after incubation with
fatty acid. Oxylipins were rapidly generated and reached maximum levels by 2-5
min. While ARA, EPA and DHA each stimulated the production of oxylipins derived
from these fatty acids themselves, ARA also stimulated the production of
oxylipins from endogenous 18- and 20-carbon fatty acids, including alpha
linolenic acid. Oxylipins generated by the lipoxygenase pathway predominated both
in resting and stimulated states. Oxylipins formed via the cytochrome P450
pathway were formed primarily from DHA and EPA, but not ARA. These data indicate
that HBMECs are capable of generating a plethora of bioactive lipids that have
the potential to modulate BBB endothelial cell function.
PMID- 26439839
TI - Nanowire CdS-CdTe Solar Cells with Molybdenum Oxide as Contact.
AB - Using a 10 nm thick molybdenum oxide (MoO3-x) layer as a transparent and low
barrier contact to p-CdTe, we demonstrate nanowire CdS-CdTe solar cells with a
power conversion efficiency of 11% under front side illumination. Annealing the
as-deposited MoO3 film in N2 resulted in a reduction of the cell's series
resistance, from 9.97 Omega/cm(2) to 7.69 Omega/cm(2), and increase in efficiency
from 9.9% to 11%. Under illumination from the back, the MoO3-x/Au side, the
nanowire solar cells yielded Jsc of 21 mA/cm(2) and efficiency of 8.67%. Our
results demonstrate use of a thin layer transition metal oxide as a potential way
for a transparent back contact to nanowire CdS-CdTe solar cells. This work has
implications toward enabling a novel superstrate structure nanowire CdS-CdTe
solar cell on Al foil substrate by a low cost roll-to roll fabrication process.
PMID- 26439838
TI - Dietary Linseed Oil Reduces Growth While Differentially Impacting LC-PUFA
Synthesis and Accretion into Tissues in Eurasian Perch (Perca fluviatilis).
AB - The aim of this study was to evaluate the impact of replacing dietary fish oil
(FO) with linseed oil (LO) on growth, fatty acid composition and regulation of
lipid metabolism in Eurasian perch (Perca fluviatilis) juveniles. Fish (17.5 g
initial body weight) were fed isoproteic and isoenergetic diets containing 116
g/kg of lipid for 10 weeks. Fish fed the LO diet displayed lower growth rates and
lower levels of DHA in the liver and muscle than fish fed the FO diet, while
mortality was not affected by dietary treatment. However, DHA content recorded in
the liver and muscle of fish fed the LO diet remained relatively high, despite a
weight gain of 134 % and a reduced dietary level of long-chain polyunsaturated
fatty acids (LC-PUFA), suggesting endogenous LC-PUFA biosynthesis. This was
supported by the higher amounts of pathway intermediates, including 18:4n-3,
20:3n-3, 20:4n-3, 18:3n-6 and 20:3n-6, recorded in the liver of fish fed the LO
diet in comparison with those fed the FO diet. However, fads2 and elovl5 gene
expression and FADS2 enzyme activity were comparable between the two groups.
Similarly, the expression of genes involved in eicosanoid synthesis was not
modulated by dietary LO. Thus, the present study demonstrated that in fish fed LO
for 10 weeks, growth was reduced but DHA levels in tissues were largely
maintained compared to fish fed FO, suggesting a physiologically relevant rate of
endogenous LC-PUFA biosynthesis capacity.
PMID- 26439840
TI - Assessment of pouch and stoma size in weight loss failure after Roux-en-Y gastric
bypass.
PMID- 26439841
TI - EP4 Receptor-Associated Protein in Macrophages Ameliorates Colitis and Colitis
Associated Tumorigenesis.
AB - Prostaglandin E2 plays important roles in the maintenance of colonic homeostasis.
The recently identified prostaglandin E receptor (EP) 4-associated protein
(EPRAP) is essential for an anti-inflammatory function of EP4 signaling in
macrophages in vitro. To investigate the in vivo roles of EPRAP, we examined the
effects of EPRAP on colitis and colitis-associated tumorigenesis. In mice, EPRAP
deficiency exacerbated colitis induced by dextran sodium sulfate (DSS) treatment.
Wild-type (WT) or EPRAP-deficient recipients transplanted with EPRAP-deficient
bone marrow developed more severe DSS-induced colitis than WT or EPRAP-deficient
recipients of WT bone marrow. In the context of colitis-associated tumorigenesis,
both systemic EPRAP null mutation and EPRAP-deficiency in the bone marrow
enhanced intestinal polyp formation induced by azoxymethane (AOM)/DSS treatment.
Administration of an EP4-selective agonist, ONO-AE1-329, ameliorated DSS-induced
colitis in WT, but not in EPRAP-deficient mice. EPRAP deficiency increased the
levels of the phosphorylated forms of p105, MEK, and ERK, resulting in activation
of stromal macrophages in DSS-induced colitis. Macrophages of DSS-treated EPRAP
deficient mice exhibited a marked increase in the expression of pro-inflammatory
genes, relative to WT mice. By contrast, forced expression of EPRAP in
macrophages ameliorated DSS-induced colitis and AOM/DSS-induced intestinal polyp
formation. These data suggest that EPRAP in macrophages functions crucially in
suppressing colonic inflammation. Consistently, EPRAP-positive macrophages were
also accumulated in the colonic stroma of ulcerative colitis patients. Thus,
EPRAP may be a potential therapeutic target for inflammatory bowel disease and
associated intestinal tumorigenesis.
PMID- 26439844
TI - The association between chronological age, age at injury and employment: Is there
a mediating effect of secondary health conditions?
AB - STUDY DESIGN: Cross-sectional observational study with data from the 2012
community-based survey of the Swiss Spinal Cord Injury Cohort Study. OBJECTIVES:
To examine the relationships between chronological age, age at injury, secondary
health conditions (SHCs) and paid employment. SETTING: Community setting in
Switzerland. METHODS: A total of 1159 individuals of working age (16-63 years for
women and 64 years for men) with traumatic or non-traumatic spinal cord injury
(SCI) were included in the study. Direct and indirect (via SHCs) effects of
chronological age and age at injury on paid employment were tested using a
decomposition method for logistic regression models. RESULTS: Both chronological
age groups (age 35-49 and 50-63/64 years) and the group with age at injury beyond
40 years showed negative direct effects on employment status. A partial indirect
effect (mediation) via chronic pain was found in the group with the highest
chronological age (>50 years). Furthermore, pressure ulcer, pain and urinary
tract infection were negatively related with employment in both models, that is,
chronological age and employment and age at injury and employment. CONCLUSION:
Being older and having a higher age at injury directly affects whether an
individual is employed. Pain is mediating the relation between chronological age
and employment. Furthermore, pressure ulcer, chronic pain and urinary tract
infection directly reduce the likelihood to be employed and, therefore, represent
important intervention targets in efforts to maintain or engage in employment of
individuals with SCI.
PMID- 26439842
TI - Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.
AB - Proteins form large macromolecular assemblies with RNA that govern essential
molecular processes. RNA-binding proteins have often been associated with
conformational flexibility, yet the extent and functional implications of their
intrinsic disorder have never been fully assessed. Here, through large-scale
analysis of comprehensive protein sequence and structure datasets we demonstrate
the prevalence of intrinsic structural disorder in RNA-binding proteins and
domains. We addressed their functionality through a quantitative description of
the evolutionary conservation of disordered segments involved in binding, and
investigated the structural implications of flexibility in terms of
conformational stability and interface formation. We conclude that the functional
role of intrinsically disordered protein segments in RNA-binding is two-fold:
first, these regions establish extended, conserved electrostatic interfaces with
RNAs via induced fit. Second, conformational flexibility enables them to target
different RNA partners, providing multi-functionality, while also ensuring
specificity. These findings emphasize the functional importance of intrinsically
disordered regions in RNA-binding proteins.
PMID- 26439846
TI - Crystallization-driven one-dimensional self-assembly of polyethylene-b-poly(tert
butylacrylate) diblock copolymers in DMF: effects of crystallization temperature
and the corona-forming block.
AB - Crystallization-driven self-assembly of polyethylene-b-poly(tert-butylacrylate)
(PE-b-PtBA) block copolymers (BCPs) in N,N-dimethyl formamide (DMF) was studied.
It is found that all three PE-b-PtBA BCPs used in this work can self-assemble
into one-dimensional crystalline cylindrical micelles. When the BCP solution is
cooled to crystallization temperature (Tc) from 130 degrees C, the seed micelles
may be produced via two competitive processes in the initial period: stepwise
micellization/crystallization and simultaneous crystallization/micellization.
Subsequently, the seed micelles can undergo growth driven by the epitaxial
crystallization of the unimers. The lengths of both the seed micelles and the
grown micelles are longer for the BCP with a longer PtBA block at a higher Tc.
Quasi-living growth of the PE-b-PtBA crystalline cylindrical micelles is achieved
at a higher Tc. A longer PtBA block evidently retards the attachment of unimers
to the crystalline micelles, leading to a slower growth rate.
PMID- 26439849
TI - Correction: Comparative Incidence of Conformational, Neurodegenerative Disorders.
PMID- 26439847
TI - Prehypertension Tsunami: A Decade Follow-Up of an Iranian Adult Population.
AB - OBJECTIVE: Prehypertension is associated with cardiovascular disease (CVD). There
is no study to examine the incidence and risk factors of prehypertension in a sex
stratified setting. The aim of this study was to examine the effect modification
of sex for different risk factors which predicts the progression from
normotension to prehypertension in a Middle East population-based cohort, during
a median follow-up of 9.2 years. METHODS: A multivariate Cox analysis was
performed among 1466 and 2131 Iranian men and women, respectively, who were free
of prehypertension, hypertension, CVD and diabetes at baseline and free of
incident hypertension without preceding prehypertension at follow-up. Incident
prehypertension at follow-up was defined as systolic blood pressure (SBP) of 120
139 mmHg and/or diastolic blood pressure (DBP) of 80-89 mmHg. RESULTS: Overall,
1440 new cases of prehypertension were identified resulting in an incidence rate
of 593/10000 person-years; the corresponding values for women and men were
489/10000 and 764/10000person-years, respectively. There were significant
interactions between gender with age, DBP, waist-to-hip-ratio (WHpR) and
estimated glomerular filtration rate (eGFR) (all P-values <0.05) in multivariate
analysis. Strong associations were found between age, body mass index (BMI) and
SBP with incident prehypertension in both genders. However, the effect of DBP and
WHpR was significant among women and 2-hour post challenge plasma glucose (2h
PCPG)was an independent risk factor for men. In the sex-adjusted analysis,
glomerular hyperfiltration [Hazard ratio (HR) and 95%CI: 1.01 (1.00-1.01), P
value = 0.02], age, BMI, WHpR, SBP and DBP had higher risks while being female
[HR (95%CI): 0.81(0.69-0.94), P-value = 0.01] had a lower risk for incident
prehypertension. CONCLUSION: According to this study results, among Iranian
population with high incidence of prehypertension, general adiposity and
glomerular hyperfiltration in total, 2h-PCPG in men and central adiposity in
women should be emphasized as risk factors for prehypertension.
PMID- 26439850
TI - Extremely Low-Frequency Electromagnetic Fields Affect the miRNA-Mediated
Regulation of Signaling Pathways in the GC-2 Cell Line.
AB - Extremely low-frequency electromagnetic fields (ELF-EMFs) can affect male
reproductive function, but the underlying mechanism of this effect remains
unknown. miRNA-mediated regulation has been implicated as an important epigenetic
mechanism for regulatory pathways. Herein, we profiled miRNA expression in
response to ELF-EMFs in vitro. Mouse spermatocyte-derived GC-2 cells were
intermittently exposed to a 50 Hz ELF-EMF for 72 h (5 min on/10 min off) at
magnetic field intensities of 1 mT, 2 mT and 3 mT. Cell viability was assessed
using the CCK-8 assay. Apoptosis and the cell cycle were analyzed with flow
cytometry. miRNA expression was profiled using Affymetrix Mouse Genechip miRNA
3.0 arrays. Our data showed that the growth, apoptosis or cell cycle arrest of GC
2 cells exposed to the 50 Hz ELF-EMF did not significantly change. However, we
identified a total of 55 miRNAs whose expression significantly changed compared
with the sham group, including 19 differentially expressed miRNAs (7 miRNAs were
upregulated, and 12 were downregulated) in the 1 mT exposure group and 36 (9
miRNAs were upregulated, and 27 were downregulated) in the 3 mT exposure group.
The changes in the expression of 15 selected miRNAs measured by real-time PCR
were consistent with the microarray results. A network analysis was used to
predict core miRNAs and target genes, including miR-30e-5p, miR-210-5p, miR-196b
5p, miR-504-3p, miR-669c-5p and miR-455-3p. We found that these miRNAs were
differentially expressed in response to different magnetic field intensities of
ELF-EMFs. GO term and KEGG pathway annotation based on the miRNA expression
profiling results showed that miRNAs may regulate circadian rhythms, cytokine
cytokine receptor interactions and the p53 signaling pathway. These results
suggested that miRNAs could serve as potential biomarkers, and the miRNA-mediated
regulation of signaling pathways might play significant roles in the biological
effects of ELF-EMFs.
PMID- 26439843
TI - Construction of recombinant adenovirus containing picorna-viral 2A-peptide
sequence for the co-expression of neuro-protective growth factors in human
umbilical cord blood cells.
AB - STUDY DESIGN: Experimental study. OBJECTIVE: Several neuro-degenerative disorders
such as Alzheimer's dementia, Parkinson's disease and amyotrophic lateral
sclerosis (ALS) are associated with genetic mutations, and replacing or
disrupting defective sequences might offer therapeutic benefits. Single gene
delivery has so far failed to achieve significant clinical improvements in
humans, leading to the advent of co-expression of multiple therapeutic genes. Co
transfection using two or more individual constructs might inadvertently result
in disproportionate delivery of the products into the cells. To prevent this, and
in order to rule out interference among the many promoters with varying strength,
expressing multiple proteins in equimolar amounts can be achieved by linking open
reading frames under the control of only one promoter. SETTING: Kazan, Russian
Federation. METHODS: Here we describe a strategy for adeno-viral co-expression of
vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2)
interconnected through picorna-viral 2A-amino-acid sequence in transfected human
umbilical cord blood mono-nuclear cells (hUCB-MCs). RESULTS: Presence of both
growth factors, as well as absence of immune response to 2A-antigen, was
demonstrated after 28-52 days. Following injection of hUCB-MCs into ALS
transgenic mice, co-expression of VEGF and FGF2, as well as viable xeno
transplanted cells, were observed in the spinal cord after 1 month. CONCLUSION:
These results suggest that recombinant adeno-virus containing 2A-sequences could
serve as a promising alternative in regenerative medicine for the delivery of
therapeutic molecules to treat neurodegenerative diseases, such as ALS.
PMID- 26439845
TI - Two-photon fluorescence lifetime imaging of primed SNARE complexes in presynaptic
terminals and beta cells.
AB - It remains unclear how readiness for Ca(2+)-dependent exocytosis depends on
varying degrees of SNARE complex assembly. Here we directly investigate the SNARE
assembly using two-photon fluorescence lifetime imaging (FLIM) of Forster
resonance energy transfer (FRET) between three pairs of neuronal SNAREs in
presynaptic boutons and pancreatic beta cells in the islets of Langerhans. These
FRET probes functionally rescue their endogenous counterparts, supporting
ultrafast exocytosis. We show that trans-SNARE complexes accumulated in the
active zone, and estimate the number of complexes associated with each docked
vesicle. In contrast, SNAREs were unassembled in resting state, and assembled
only shortly prior to insulin exocytosis, which proceeds slowly. We thus
demonstrate that distinct states of fusion readiness are associated with SNARE
complex formation. Our FRET/FLIM approaches enable optical imaging of fusion
readiness in both live and chemically fixed tissues.
PMID- 26439848
TI - Studies on Immunogenicity and Antigenicity of Baculovirus-Expressed Binding
Region of Plasmodium falciparum EBA-140 Merozoite Ligand.
AB - The erythrocyte binding ligand 140 (EBA-140) is a member of the Plasmodium
falciparum erythrocyte binding antigens (EBA) family, which are considered as
prospective candidates for malaria vaccine development. EBA proteins were
identified as important targets for naturally acquired inhibitory antibodies.
Natural antibody response against EBA-140 ligand was found in individuals living
in malaria-endemic areas. The EBA-140 ligand is a paralogue of the well
characterized P. falciparum EBA-175 protein. They both share homology of domain
structure, including the binding region (Region II), which consists of two
homologous F1 and F2 domains and is responsible for ligand-erythrocyte receptor
interaction during merozoite invasion. It was shown that the erythrocyte receptor
for EBA-140 ligand is glycophorin C-a minor human erythrocyte sialoglycoprotein.
In studies on the immunogenicity of P. falciparum EBA ligands, the recombinant
proteins are of great importance. In this report, we have demonstrated that the
recombinant baculovirus-obtained EBA-140 Region II is immunogenic and antigenic.
It can raise specific antibodies in rabbits, and it is recognized by natural
antibodies present in sera of patients with malaria, and thus, it may be
considered for inclusion in multicomponent blood-stage vaccines.
PMID- 26439851
TI - Variable-Selection Emerges on Top in Empirical Comparison of Whole-Genome Complex
Trait Prediction Methods.
AB - Accurate prediction of complex traits based on whole-genome data is a
computational problem of paramount importance, particularly to plant and animal
breeders. However, the number of genetic markers is typically orders of magnitude
larger than the number of samples (p >> n), amongst other challenges. We assessed
the effectiveness of a diverse set of state-of-the-art methods on publicly
accessible real data. The most surprising finding was that approaches with
feature selection performed better than others on average, in contrast to the
expectation in the community that variable selection is mostly ineffective, i.e.
that it does not improve accuracy of prediction, in spite of p >> n. We observed
superior performance despite a somewhat simplistic approach to variable
selection, possibly suggesting an inherent robustness. This bodes well in general
since the variable selection methods usually improve interpretability without
loss of prediction power. Apart from identifying a set of benchmark data sets
(including one simulated data), we also discuss the performance analysis for each
data set in terms of the input characteristics.
PMID- 26439853
TI - Monolayer-by-monolayer stacked pyramid-like MoS2 nanodots on monolayered MoS2
flakes with enhanced photoluminescence.
AB - The precise control of the morphology and crystal shape of MoS2 nanostructures is
of particular importance for their application in nanoelectronic and
optoelectronic devices. Here, we describe a single step route for the synthesis
of monolayer-by-monolayer stacked pyramid-like MoS2 nanodots on monolayered MoS2
flakes using a chemical vapor deposition method. First-principles calculations
demonstrated that the bandgap of the pyramid-like MoS2 nanodot is a direct
bandgap. Enhanced local photoluminescence emission was observed in the pyramid
like MoS2 nanodot, in comparison with monolayered MoS2 flakes. The findings
presented here provide new opportunities to tailor the physical properties of
MoS2via morphology-controlled synthesis.
PMID- 26439855
TI - Pneumatically-actuated artificial cilia array for biomimetic fluid propulsion.
AB - Arrays of beating cilia emerged in nature as one of the most efficient propulsion
mechanisms at a small scale, and are omnipresent in microorganisms. Previous
attempts at mimicking these systems have foundered against the complexity of
fabricating small-scale cilia exhibiting complex beating motions. In this paper,
we propose for the first time arrays of pneumatically-actuated artificial cilia
that are able to address some of these issues. These artificial cilia arrays
consist of six highly flexible silicone rubber actuators with a diameter of 1 mm
and a length of 8 mm that can be actuated independently from each other. In an
experimental setup, the effects of the driving frequency, phase difference and
duty cycle on the net flow in a closed-loop channel have been studied. Net fluid
speeds of up to 19 mm s(-1) have been measured. Further, it is possible to invert
the flow direction by simply changing the driving frequency or by changing the
duty cycle of the driving block pulse pressure wave without changing the bending
direction of the cilia. Using PIV measurements, we corroborate for the first time
existing mathematical models of cilia arrays to measurements on prototypes.
PMID- 26439852
TI - Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro
and In Vivo Evaluations.
AB - In recent years, the diagnostic and therapeutic uses of radioisotopes have shown
significant progress. Immunoglobulin (Ig) appears to be a promising tracer,
particularly due to its ability to target selected antigens. The main objective
of this study is to optimize and assess an Ig radiolabeling method with
Technetium 99m (99mTc), an attractive radioelement used widely for diagnostic
imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo
radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was
radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling
stability was evaluated over 24h by thin-layer chromatography. IgG integrity was
checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with
Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was
assessed in vitro by a radioimmunoassay method and binding experiments with cells
(EL4-hCD20 and EL4-WT). Biodistribution studies were performed in normal BALB/c
mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous
xenografts. With optimized method, high radiolabeling yields were obtained (95.9
+/- 3.5%). 99mTc-IgG-SH was stable in phosphate-buffered saline (4 degrees C and
25 degrees C) and in serum (37 degrees C), even if important sensitivity to
transchelation was observed. IgG was not degraded by derivatization and
radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti
CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo
biodistribution studies for 48h showed significant accumulation of radioactivity
in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing
tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor
versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was
effective, stable and required few antibody amounts. This attractive
radiolabeling method is "antibody safe" and preserves Ig affinity for antigen, as
shown by both in vitro and in vivo experiments. This method could easily be used
with noncommercial IgG or other antibody isotypes.
PMID- 26439854
TI - Maternal Telomere Length and Risk of Down Syndrome: Epidemiological Impact of
Smokeless Chewing Tobacco and Oral Contraceptive on Segregation of Chromosome 21.
AB - BACKGROUND: We have previously demonstrated a relationship between children born
with Down syndrome and maternal telomere length. Similarly, exposure to tobacco
and oral contraceptives has been explored in one of our earlier studies as a risk
factor for Down syndrome. OBJECTIVE: In the present study, we consider the
interactions among these risk factors associated with Down syndrome in a
population from Kolkata, India, using analyses stratified by maternal age.
METHODS: We estimated the telomere length of women with children with Down
syndrome by restriction enzyme/Southern blot methods. Linear regression was
employed to estimate telomere shortening as an indicator of the maternal age of
conception. Interactions among the various factors were analyzed by logistic
regression. RESULT: We found an association between the use of smokeless chewing
tobacco and shorter telomere length among women who experienced meiosis I
nondisjunction at gametogenesis; the effect is seen across all maternal age
groups. In contrast, oral contraceptive use alone did not exhibit a statistically
significant association with maternal telomere length, but there was an
interaction with the use of smokeless chewing tobacco in the older mothers who
experienced meiotic II nondisjunction. CONCLUSION: Environmental/habitual factors
interact with molecular components of the oocyte, which ultimately increases the
risk of chromosome 21 nondisjunction and subsequently of giving birth to a child
with Down syndrome.
PMID- 26439856
TI - Barriers to early prenatal care in South Africa.
AB - OBJECTIVE: To understand the barriers delaying early prenatal care for women in
South Africa. METHODS: A mixed-methods study was conducted at a center in
Pretoria. RESULTS: Following interviews with 21 women at a prenatal clinic in
Pretoria, a quantitative survey was completed by 204 postpartum women. During
interviews, women described presenting late owing to contemplating induced
abortion, fear of HIV testing, and fear of jealousy and bewitching. The survey
results demonstrated that a majority of women (133 [65.2%]) reported knowledge of
recommendations to present before 12weeks; however, the average gestational age
at initial presentation was 19.1+/-7.7weeks. Women were more likely to present
earlier if the pregnancy was planned (P=0.013) and were less likely to if they
had at any point contemplated induced abortion (P=0.021). Fears of bewitching and
harmful psychological stress owing to a positive HIV test result prevailed in
both the interviews and the surveys. CONCLUSION: Significant efforts should be
devoted to improving access to contraception and prepregnancy counseling in order
to improve early prenatal care attendance. Similarly, addressing cultural
concerns and fears regarding pregnancy is imperative in promoting early
attendance.
PMID- 26439857
TI - Glucosensing in liver and Brockmann bodies of rainbow trout through glucokinase
independent mechanisms.
AB - We hypothesize that glucosensor mechanisms other than that mediated by
glucokinase (GK) are present in the liver and Brockmann bodies (BB) of rainbow
trout, and are affected by stress. We evaluated in these tissues changes in
parameters related to putative glucosensor mechanisms based on liver X receptor
(LXR), mitochondrial activity, sweet taste receptor, and SGLT-1 6h after
intraperitoneal injection of saline solution alone (normoglycaemic treatment) or
containing insulin (hypoglycaemic treatment), or d-glucose (hyperglycaemic
treatment). Half of tanks were kept at normal stocking density (NSD;
10kgfishmass.m(-3)) whereas the remaining tanks were kept at high stocking
density (HSD; 70kgfishmass.m(-3)). The results provide for the first time in fish
evidence for the presence of putative glucosensor systems based on mitochondrial
activity and sweet taste receptor in liver whereas in BB systems based on LXR,
mitochondrial activity, sweet taste receptor, and SGLT-1 could be operative. We
also obtained for the first time in fish evidence for the functioning of
integrative metabolic sensors in response to changes in nutrient levels since
changes in the mRNA abundance of sirtuin 1 (SIRT-1) were observed in response to
increased glucose levels. The stress conditions elicited by HSD altered the
response of the glucosensor systems based on mitochondrial activity, sweet taste
receptor, and SGLT-1 in the liver, and LXR and SGLT-1 in the BB.
PMID- 26439859
TI - A Monte Carlo simulation for the estimation of patient dose in rest and stress
cardiac computed tomography with a 320-detector row CT scanner.
AB - PURPOSE: To estimate organ dose and effective dose for patients for cardiac CT as
applied in an international multicenter study (CORE320) with a 320-Detector row
CT scanner using Monte Carlo (MC) simulations and voxelized phantoms. The effect
of positioning of the arms, off-centering the patient and heart rate on patient
dose was analyzed. METHODS: A MC code was tailored to simulate the geometry and
characteristics of the CT scanner. The phantoms representing the adult reference
male and female were implemented according to ICRP 110. Effective dose and organ
doses were obtained for CT acquisition protocols for calcium scoring, coronary
angiography and myocardial perfusion. RESULTS: For low heart rate, the normalized
effective dose (E) for cardiac CT was higher for female (5.6 mSv/100 mAs)
compared to male (2.2 mSv/100 mAs) due to the contribution of female breast
tissue. Averaged E for female and male was 11.3 mSv for the comprehensive cardiac
protocol consisting of calcium scoring (1.9 mSv); coronary angiography including
rest cardiac perfusion (5.1 mSv) and stress cardiac perfusion (4.3 mSv). These
values almost doubled at higher heart rates (20.1 mSv). Excluding the arms
increased effective dose by 6-8%, centering the patient showed no significant
effect. The k-factor (0.028 mSv/mGy.cm) derived from this study leads to
effective doses up to 2-3 times higher than the values obtained using now
outdated methodologies. CONCLUSION: MC modeling of cardiac CT examinations on
realistic voxelized phantoms allowed us to assess patient doses accurately and we
derived k-factors that are well above those published previously.
PMID- 26439862
TI - Impacts of management and climate change on nitrate leaching in a forested karst
area.
AB - Forest management and climate change, directly or indirectly, affect drinking
water resources, both in terms of quality and quantity. In this study in the
Northern Limestone Alps in Austria we have chosen model calculations
(LandscapeDNDC) in order to resolve the complex long-term interactions of
management and climate change and their effect on nitrogen dynamics, and the
consequences for nitrate leaching from forest soils into the karst groundwater.
Our study highlights the dominant role of forest management in controlling
nitrate leaching. Both clear-cut and shelterwood-cut disrupt the nitrogen cycle
to an extent that causes peak concentrations and high fluxes into the seepage
water. While this effect is well known, our modelling approach has revealed
additional positive as well as negative impacts of the expected climatic changes
on nitrate leaching. First, we show that peak nitrate concentrations during post
cutting periods were elevated under all climate scenarios. The maximal effects of
climatic changes on nitrate concentration peaks were 20-24 mg L(-1) in 2090 with
shelterwood or clear-cut management. Second, climate change significantly
decreased the cumulative nitrate losses over full forest rotation periods (by 10
20%). The stronger the expected temperature increase and precipitation decrease
(in summer), the lesser were the observed nitrate losses. However, mean annual
seepage water nitrate concentrations and cumulative nitrate leaching were higher
under continuous forest cover management than with shelterwood-cut and clear-cut
systems. Watershed management can thus be adapted to climate change by either
reducing peak concentrations or long-term loads of nitrate in the karst
groundwater.
PMID- 26439861
TI - Simulation and optimization of a coking wastewater biological treatment process
by activated sludge models (ASM).
AB - Applications of activated sludge models (ASM) in simulating industrial biological
wastewater treatment plants (WWTPs) are still difficult due to refractory and
complex components in influents as well as diversity in activated sludges. In
this study, an ASM3 modeling study was conducted to simulate and optimize a
practical coking wastewater treatment plant (CWTP). First, respirometric
characterizations of the coking wastewater and CWTP biomasses were conducted to
determine the specific kinetic and stoichiometric model parameters for the
consecutive aeration-anoxic-aeration (O-A/O) biological process. All ASM3
parameters have been further estimated and calibrated, through cross validation
by the model dynamic simulation procedure. Consequently, an ASM3 model was
successfully established to accurately simulate the CWTP performances in removing
COD and NH4-N. An optimized CWTP operation condition could be proposed reducing
the operation cost from 6.2 to 5.5 ?/m(3) wastewater. This study is expected to
provide a useful reference for mathematic simulations of practical industrial
WWTPs.
PMID- 26439858
TI - Characterisation of grids of point detectors in maximum skin dose measurement in
fluoroscopically-guided interventional procedures.
AB - PURPOSE: Point detectors are frequently used to measure patient's maximum skin
dose (MSD) in fluoroscopically-guided interventional procedures (IP). However,
their performance and ability to detect the actual MSD are rarely evaluated. The
present study investigates the sampling uncertainty associated with the use of
grids of point detectors to measure MSD in IP. METHOD: Chemoembolisation of the
liver (CE), percutaneous coronary intervention (PCI) and neuroembolisation (NE)
procedures were studied. Spatial dose distributions were measured with XR-RV3
Gafchromic((r)) films for 176 procedures. These distributions were used to
simulate measurements performed using grids of detectors such as
thermoluminescence detectors, with detector spacing from 1.4 up to 10 cm.
RESULTS: The sampling uncertainty was the highest in PCI and NE procedures. With
40 detectors covering the film area (36 cm * 44 cm), the maximum dose would be on
average 86% and 63% of the MSD measured with Gafchromic((r)) films in CE and PCI
procedures, respectively. In NE procedures, with 27 detectors covering the film
area (14 cm * 35 cm), the maximum dose measured would be on average 82% of the
MSD obtained with the Gafchromic((r)) films. CONCLUSION: Thermoluminescence
detectors show good energy and dose response in clinical beam qualities. However
the poor spatial resolution of such point-like dosimeters may far outweigh their
good dosimetric properties. The uncertainty from the sampling procedure should be
estimated when point detectors are used in IP because it may lead to strong
underestimation of the MSD.
PMID- 26439860
TI - Rapid enhanced photocatalytic degradation of dyes using novel N-doped ZrO2.
AB - A novel N-doped ZrO2 (N-ZrO2) photocatalyst is synthesized through thermal
decomposition of zirconium hydroxide-urea complex and is characterized using
various techniques, including XRD, FTIR, TGA, SEM, TEM, UV-DRS, XPS, XANES, and
BET. The N-ZrO2 possesses pure monoclinic structure with high crystallinity. By
using the proposed facile route of synthesis, both interstitial and
substitutional N doping with high dopant stability can be realized. The optical
properties of the catalyst are significantly altered after N doping, giving an
optical response in the visible and near infrared regions and an additional
strong absorption peak in the UVA region. The N-ZrO2 showed a higher
photocatalytic activity than pristine ZrO2 for the degradation of amaranth (AM)
and methylene blue (MB) under visible or UV light irradiation, which could be
attributed to the band gap narrowing, higher specific area, smaller crystalline
size, and higher availability of surface hydroxyl groups. Due to its molecular
structure and light absorption characteristics, MB is easier to degrade than AM.
Overall removal efficiencies, including adsorption and photolysis, for AM and MB
by N-ZrO2 at pH 7 with initial dye concentration of 10 mg/L, catalyst
concentration of 1 g/L, and visible light irradiation of 144.7 W/m(2) are 67.2
and 96%, respectively. Using UVA light of only 3.5 W/m(2) under identical
experimental conditions, complete removal of MB and AM is obtained. The
photocatalytically treated solution of either AM or MB is nontoxic against
Bacillus cereus, an agriculturally important soil microorganism.
PMID- 26439864
TI - Quantitative Imaging of Gut Microbiota Spatial Organization.
AB - Genomic technologies have significantly advanced our understanding of the
composition and diversity of host-associated microbial populations. However,
their spatial organization and functional interactions relative to the host have
been more challenging to study. Here we present a pipeline for the assessment of
intestinal microbiota localization within immunofluorescence images of fixed gut
cross-sections that includes a flexible software package, BacSpace, for high
throughput quantification of microbial organization. Applying this pipeline to
gnotobiotic and human microbiota-colonized mice, we demonstrate that elimination
of microbiota-accessible carbohydrates (MACs) from the diet results in thinner
mucus in the distal colon, increased proximity of microbes to the epithelium, and
heightened expression of the inflammatory marker REG3beta. Measurements of
microbe-microbe proximity reveal that a MAC-deficient diet alters monophyletic
spatial clustering. Furthermore, we quantify the invasion of Helicobacter pylori
into the glands of the mouse stomach relative to host mitotic progenitor cells,
illustrating the generalizability of this approach.
PMID- 26439865
TI - Pathogen Virulence Impedes Mutualist-Mediated Enhancement of Host Juvenile Growth
via Inhibition of Protein Digestion.
AB - The microbial environment impacts many aspects of metazoan physiology through
largely undefined molecular mechanisms. The commensal strain Lactobacillus
plantarum(WJL) (Lp(WJL)) sustains Drosophila hormonal signals that coordinate
systemic growth and maturation of the fly. Here we examine the underlying
mechanisms driving these processes and show that Lp(WJL) promotes intestinal
peptidase expression, leading to increased intestinal proteolytic activity,
enhanced dietary protein digestion, and increased host amino acid levels. Lp(WJL)
mediated peptidase upregulation is partly driven by the peptidoglycan recognition
and signaling cascade PGRP-LE/Imd/Relish. Additionally, this mutualist-mediated
physiological benefit is antagonized upon pathogen infection. Pathogen virulence
selectively impedes Lp(WJL)-mediated intestinal peptidase activity enhancement
and juvenile growth promotion but does not alter growth of germ-free animals. Our
study reveals the adaptability of host physiology to the microbial environment,
whereby upon acute infection the host switches to pathogen-mediated host immune
defense at the expense of mutualist-mediated growth promotion.
PMID- 26439863
TI - Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid
Metabolism by Vpu and Nef.
AB - Critical cell surface immunoreceptors downregulated during HIV infection have
previously been identified using non-systematic, candidate approaches. To gain a
comprehensive, unbiased overview of how HIV infection remodels the T cell
surface, we took a distinct, systems-level, quantitative proteomic approach. >100
plasma membrane proteins, many without characterized immune functions, were
downregulated during HIV infection. Host factors targeted by the viral accessory
proteins Vpu or Nef included the amino acid transporter SNAT1 and the serine
carriers SERINC3/5. We focused on SNAT1, a beta-TrCP-dependent Vpu substrate.
SNAT1 antagonism was acquired by Vpu variants from the lineage of SIVcpz/HIV-1
viruses responsible for pandemic AIDS. We found marked SNAT1 induction in
activated primary human CD4+ T cells, and used Consumption and Release (CoRe)
metabolomics to identify alanine as an endogenous SNAT1 substrate required for T
cell mitogenesis. Downregulation of SNAT1 therefore defines a unique paradigm of
HIV interference with immunometabolism.
PMID- 26439867
TI - Adolescent vulnerability and the distress of rejection: Associations of
adjustment problems and gender with control, emotions, and coping.
AB - We examined adjustment problems as risks for patterns of emotions, appraisals,
and coping with rejection, and explored whether these processes could account for
sex (boy/girl) differences in coping. Young adolescents (N = 669, grades 6-8)
completed questionnaires, which assessed responses to peer rejection threat with
two short scenarios. Using structural equation modeling to test a multivariate
process model, adolescents with heightened social anxiety had the most
maladaptive responses to rejection threat, including elevated emotional
reactions, more self-blame, and coping using more social isolation, rumination
and opposition. Adolescents reporting more depressive symptoms felt less control
and anticipated using less adaptive coping (less support seeking, distraction,
and negotiation), whereas aggressive adolescents responded with more anger and
coped via opposition. Moreover, as anticipated, sex differences in coping,
symptoms, emotions, and appraisals were found. However, coping differences
between boys and girls were mostly nonsignificant after accounting for symptoms,
aggression, emotional reactions, and appraisals.
PMID- 26439868
TI - The effects of pubertal timing on externalizing behaviors in adolescence and
early adulthood: A meta-analytic review.
AB - Using a meta-analytic approach, this investigation examines the association
between early pubertal timing and externalizing behaviors in adolescence and
early adulthood. The findings showed that the effect size of early pubertal
maturation on externalizing behaviors was r = 0.180. This small, yet significant
effect size is consistent with the models of early pubertal maturation in that
early maturation is associated with higher levels of externalizing behaviors.
Using contrast analyses, we examined three potential moderators of this
association: sex, the concurrent versus long-term effect of early puberty, and
types of puberty assessments. Neither sex nor type of pubertal timing assessment
moderated the effect significantly. However, results indicated that the effect
was stronger for studies that measured pubertal timing and externalizing
behaviors concurrently rather than longitudinally (i.e., examining prospective
effect of pubertal timing on later externalizing behaviors). The findings are
discussed in terms of implications for future research.
PMID- 26439866
TI - School-related social support and subjective well-being in school among
adolescents: The role of self-system factors.
AB - This 6-week longitudinal study aimed to examine a moderated mediation model that
may explain the link between school-related social support (i.e., teacher support
and classmate support) and optimal subjective well-being in school among
adolescents (n = 1316). Analyses confirmed the hypothesized model that scholastic
competence partially mediated the relations between school-related social support
and subjective well-being in school, and social acceptance moderated the
mediation process in the school-related social support--> subjective well-being
in school path and in the scholastic competence--> subjective well-being in
school path. The findings suggested that both social contextual factors (e.g.,
school-related social support) and self-system factors (e.g., scholastic
competence and social acceptance) are crucial for adolescents' optimal subjective
well-being in school. Limitations and practical applications of the study were
discussed.
PMID- 26439869
TI - Age estimation of decomposed bodies based on a combined arteriosclerotic index.
AB - Several methods exist for the estimation of the age at the time of death, ranging
from mere visual inspection to costly laboratory examinations. The "combined
arteriosclerotic index (CAI)" is considered to be a suitable low-budget tool for
undecayed corpses. It defines the ratio between diameter and longitudinal pre
strain of the abdominal aorta. Its applicability in cases of decomposed corpses
has not been studied yet. We examined whether it is a valid parameter in
putrefied bodies as well and whether there is a correlation between CAI and the
stage of decomposition. In conclusion the CAI becomes less accurate with
increasing putrefaction. Nonetheless, even in case of high-grade putrefaction it
remains a useful tool for instant age estimation which should be followed by the
application of methods with higher accuracy.
PMID- 26439870
TI - Characteristics of methadone-related fatalities in Norway.
AB - There are currently over 7000 patients enrolled in opioid maintenance treatment
(OMT) programs in Norway. A rise in methadone-related deaths proportional to
increasing methadone sales over the period 2000-2006 has been observed, but the
causative factors for these fatalities have been elusive. In the present study,
individual characteristics, methadone concentrations and additional toxicological
findings were analyzed. Methadone intoxication deaths (n = 264) were divided into
3 groups according to toxicological findings in whole blood: group 1 - methadone
detected alone, or together with one additional drug at low or therapeutic
levels, or a low concentration of ethanol (<1 g/L) (n = 21); group 2 - multiple
additional drugs/substances detected below lethal levels (n = 175); group 3 - one
or more additional drugs/substances detected at lethal levels, or ethanol >3 g/L
(n = 55). Methadone blood concentrations in decedents who had been enrolled in
OMT were higher than for decedents not in treatment, in all groups. Blood
methadone concentrations around 1 mg/L were present in fatal multi-drug
intoxications in OMT patients. Results suggest that some patients may be at risk
of dying when combining therapeutic concentrations of methadone with other
psychoactive substances. Somatic disease was a common finding among deceased OMT
patients. Concentrations in methadone users not enrolled in OMT were
predominantly between 0.3 and 0.4 mg/L and were not related to the presence of
other drugs. However, methadone concentrations below 0.1 mg/L may be associated
with intoxication following methadone use, both alone and in combination with
other drugs. Younger male users (mean age 34 years) seemed to have a higher
susceptibility to methadone intoxication.
PMID- 26439871
TI - [An update on adenomyosis and implantation].
AB - Adenomyosis is an enigmatic disease whose impact on implantation and fertility
outcome is still controversial. A negative effect on IVF outcome was already
observed, but it is mainly explained by an increase in early spontaneous
miscarriages. We reviewed scientific data in order to bring relevant information
about adenomyosis and endometrial receptivity for patient counselling and to
precise if screening of adenomyosis is indicated before IVF treatment.
PMID- 26439872
TI - [Assessment of a multidisciplinary care for 169 excised women with an initial
reconstructive surgery project].
AB - OBJECTIVE: To assess the benefits of a multidisciplinary care among excised women
with an initial surgery project and identify the reasons for discarding surgery.
METHODS: Descriptive and retrospective study performed between the 1st of January
2006 and the 31st of December 2011 at the Armand Trousseau Hospital, Paris. All
excised patients went through consultations with a mid-wife, a sexologist, a
psychologist, a gynaecologist-obstetrician and, for some of them, underwent a
clitoral reconstructive surgery. RESULTS: One hundred and sixty-nine patients
were included: among them, 61 patients (36%) were operated and 108 patients (64%)
have given spontaneously to surgery, 32% being reinforced by consultation. Ninety
one on 111 patients (82%) respondents were satisfied with their care pathway. The
main motivation was to support identity for 39 patients operated (64%) while
improving sex prevailed for 56 non-operated patients (52%). The study evidenced
an improvement of the functional and sexual life quality after surgery: 17%
experienced an orgasm versus 2% before surgery, 56% reported an increase in their
libido and 41% a decrease in dyspareunia. CONCLUSION: Clitoral reconstructive
surgery with multidisciplinary care tends to improve the functional and sexual
life quality of excised patients, though it is not always necessary. Some of the
patients discard their initial project of reconstructive surgery as in some of
the cases, a multidisciplinary care only seems sufficient.
PMID- 26439873
TI - Transcranial direct current stimulation in treatment-resistant obsessive
compulsive disorder: An open-label pilot study.
AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is a severe mental illness. OCD
symptoms are often resistant to available treatments. Abnormalities within the
orbitofronto-striato-pallido-thalamic circuitry, especially orbitofrontal cortex
(OFC) hyperactivity and cerebellar hypoactivity have been observed in patients.
Non-invasive brain stimulation studies have indicated that transcranial direct
current stimulation (tDCS) may be a useful alternative to alleviate treatment
resistant symptoms in various neuropsychiatric conditions. METHODS: In an open
label pilot study, 8 patients with treatment-resistant OCD received 10 sessions
(twice a day) of 2mA tDCS applied with the cathode over the left OFC and the
anode over the right cerebellum. OCD (Y-BOCS and OCD-VAS) as well as depressive
(MADRS) symptoms were measured 4 times: one time before tDCS and 3 times after
(immediately after, 1 and 3months after the 10th tDCS session). RESULTS: We
reported a significant 26.4% (+/-15.8) decrease of Y-BOCS score (p=0.002). The
beneficial effect lasted during the 3month follow-up. No effect of tDCS was
observed on depressive symptoms. At end point, 5 out of 8 patients had a decrease
of >=25%; and 3 out of 8 patients had a decrease of >=35% in Y-BOCS score. tDCS
was well tolerated. CONCLUSION: tDCS with the cathode placed over the left OFC
combined with the anode placed over the right cerebellum is a suitable and safe
approach to decrease OCD symptoms in patients with treatment-resistant OCD. Large
scale randomized controlled studies are needed to confirm this promising result.
PMID- 26439874
TI - Synthesis and Analysis of the Structure, Diffusion and Cytotoxicity of
Heterocyclic Platinum(IV) Complexes.
AB - We have developed six dihydroxidoplatinum(IV) compounds with cytotoxic potential.
Each derived from active platinum(II) species, these complexes consist of a
heterocyclic ligand (HL) and ancillary ligand (AL) in the form
[Pt(HL)(AL)(OH)2](2+), where HL is a methyl-functionalised variant of 1,10
phenanthroline and AL is the S,S or R,R isomer of 1,2-diaminocyclohexane. NMR
characterisation and X-ray diffraction studies clearly confirmed the coordination
geometry of the octahedral platinum(IV) complexes. The self-stacking of these
complexes was determined using pulsed gradient stimulated echo nuclear magnetic
resonance. The self-association behaviour of square planar platinum(II) complexes
is largely dependent on concentration, whereas platinum(IV) complexes do not
aggregate under the same conditions, possibly due to the presence of axial
ligands. The cytotoxicity of the most active complex, exhibited in several cell
lines, has been retained in the platinum(IV) form.
PMID- 26439875
TI - Catalytic C-H bond functionalisation chemistry: the case for quasi-heterogeneous
catalysis.
AB - This feature article examines the potential of heterogeneous Pd species to
mediate catalytic C-H bond functionalisation processes employing suitable
substrates (e.g. aromatic/heteroaromatic compounds). A focus is placed on the
reactivity of supported and non-supported Pd nanoparticle (PdNPs) catalysts, in
addition to the re-appropriation of well-established heterogeneous Pd catalysts
such as Pd/C. Where possible, reasonable comparisons are made between PdNPs and
traditional 'homogeneous' Pd precatalyst sources (which form PdNPs). The
involvement of higher order Pd species in traditional cross-coupling processes,
such as Mizoroki-Heck, Sonogashira and Suzuki-Miyaura reactions, allows the
exemplification of potential future topics for study in the area of catalytic C-H
bond functionalisation processes.
PMID- 26439877
TI - The favourable effects of long-term selenium supplementation on regression of
cervical tissues and metabolic profiles of patients with cervical intraepithelial
neoplasia: a randomised, double-blind, placebo-controlled trial.
AB - This study was conducted to assess the effects of long-term Se administration on
the regression and metabolic status of patients with cervical intraepithelial
neoplasia grade 1 (CIN1). This randomised, double-blind, placebo-controlled trial
was carried out among fifty-eight women diagnosed with CIN1. To diagnose CIN1, we
used specific diagnostic procedures of biopsy, pathological diagnosis and
colposcopy. Patients were randomly assigned to two groups to receive 200 MUg Se
supplements as Se yeast (n 28) or placebo (n 28) daily for 6 months. After 6
months of taking Se supplements, a greater percentage of women in the Se group
had regressed CIN1 (88.0 v. 56.0 %; P=0.01) compared with those in the placebo
group. Long-term Se supplementation, compared with the placebo, resulted in
significant decreases in fasting plasma glucose levels (-0.37 (sd 0.32) v. +0.07
(sd 0.63) mmol/l; P=0.002), serum insulin levels (-28.8 (sd 31.2) v. +13.2 (sd
40.2) pmol/l; P<0.001), homeostatic model assessment of insulin resistance values
(-1.3 (se 1.3) v. +0.5 (se 1.4); P<0.001) and a significant elevation in
quantitative insulin sensitivity check index (+0.03 (sd 0.03) v. -0.01 (sd 0.01);
P<0.001). In addition, patients who received Se supplements had significantly
decreased serum TAG (-0.14 (sd 0.55) v. +0.15 (sd 0.38) mmol/l; P=0.02) and
increased HDL-cholesterol levels (+0.13 (sd 0.21) v. -0.01 (sd 0.15) mmol/l;
P=0.003). In addition, compared with the placebo group, there were significant
rises in plasma total antioxidant capacity (+186.1 (sd 274.6) v. +42.8 (sd 180.4)
mmol/l; P=0.02) and GSH levels (+65.0 (sd 359.8) v. -294.2 (sd 581.8) MUmol/l;
P=0.007) and a significant decrease in malondialdehyde levels (-1.5 (sd 2.1) v.
+0.1 (sd 1.4) MUmol/l; P=0.001) among those who took Se supplements. Overall,
taking Se supplements among patients with CIN1 led to its regression and had
beneficial effects on their metabolic profiles.
PMID- 26439876
TI - The IP3 R Binding Protein Released With Inositol 1,4,5-Trisphosphate Is Expressed
in Rodent Reproductive Tissue and Spermatozoa.
AB - Besides its capacity to inhibit the 1,4,5-trisphosphate (IP3) receptor, the
regulatory protein IRBIT (IP3 receptor binding protein released with IP3) is also
able to control the activity of numerous ion channels and electrolyte
transporters and thereby creates an optimal electrolyte composition of various
biological fluids. Since a reliable execution of spermatogenesis and sperm
maturation critically depends on the establishment of an adequate
microenvironment, the expression of IRBIT in male reproductive tissue was
examined using immunohistochemical approaches combined with biochemical
fractionation methods. The present study documents that IRBIT is expressed in
Leydig and Sertoli cells. In addition, pronounced IRBIT expression was detected
in sperm precursors during early stages of spermatogenesis as well as in
spermatozoa. Analyzing tissue sections of rodent epididymides, IRBIT was found to
co-localize with the proton pumping V-ATPase and the cystic fibrosis
transmembrane conductance regulator (CFTR) at the apical surface of narrow and
clear cells. A similar co-localization of IRBIT with CFTR was also observed for
Sertoli cells and developing germ cells. Remarkably, assaying caudal sperm in
immunogold electron microscopy, IRBIT was found to localize to the acrosomal cap
and the flagellum as well as to the sperm nucleus; moreover, a prominent
oligomerization was observed for spermatozoa. The pronounced occurrence of IRBIT
in the male reproductive system and mature spermatozoa indicates a potential role
for IRBIT in establishing the essential luminal environment for a faithful
execution of spermatogenesis and epididymal sperm maturation, and suggest a
participation of IRBIT during maturation steps after ejaculation and/or the final
fertilization process.
PMID- 26439878
TI - Tumor-derived microvesicles in the tumor microenvironment: How vesicle
heterogeneity can shape the future of a rapidly expanding field.
AB - Information transmission from tumor cells to non-tumor cells in the surrounding
microenvironment via microvesicles is a more recently studied form of
intercellular signaling that can have a marked impact on the tumor
microenvironment. Tumor-derived microvesicles (TMVs) are packed with information
including signaling proteins and nucleic acids, and can be taken up by target
cells, enabling paracrine signaling. While previous research has focused on how
vesicles released from pathologic cells differ from normal cells, the
heterogeneity that exists within the TMV population itself is not fully
characterized, and only beginning to be appreciated. In this review, we summarize
current understanding of the biogenesis and roles of shed TMVs in the tumor
microenvironment, and speculate on the consequences for tumor cell signaling in
light of the hypothesis that there exists variance within the TMV population. The
analysis of differential signaling upon cell-TMV interactions provides insights
into potential mechanisms of intercellular communication.
PMID- 26439879
TI - On the relative abundance of autopolyploids and allopolyploids.
PMID- 26439880
TI - Serum club cell protein 16 is associated with asymptomatic airway responsiveness
in adults: Findings from the French epidemiological study on the genetics and
environment of asthma.
AB - BACKGROUND AND OBJECTIVE: Club cell secretory protein (CC-16) is a sensitive
biomarker of airways epithelium integrity. It has gained interest as a biological
marker in chronic lung diseases because of its presumed relationship to
inflammation. Little is known about the association between CC-16 serum level and
asthma, lung function and airway responsiveness (AR). METHODS: Serum CC-16 level
was determined by latex immunoassay in 1298 participants from the French
Epidemiological case-control and family-based study on Genetics and Environment
of Asthma (EGEA) (mean age 43 years; 49% men, 38% with asthma). Pre
bronchodilator lung function (forced expiratory volume in 1 s (FEV1 ), forced
vital capacity (FVC) and FEV1 /FVC) and degree of AR, expressed as a function of
the dose-response slope to methacholine test were measured. Standardized
residuals CC-16 z-scores were obtained by regressing CC-16 level on the
glomerular filtration rate. CC-16 z-scores were correlated with asthma, lung
function and AR in participants with and without asthma. RESULTS: CC-16 geometric
mean level was 12.4 MUg/L (range: 2.2-70.6 MUg/L). In participants without
asthma, lower CC-16 z-scores was associated with impaired FEV1 /FVC% (beta = 0.50
(95% CI: 0.06, 0.95) and with higher degree of AR (beta = 0.24 (95% CI: 0.09,
0.39)). CC-16 was not associated with impaired lung function or AR in
participants with asthma. CONCLUSIONS: Lower CC-16 serum level was associated
with impaired lung function and AR, suggesting that serum CC-16 level may reflect
early damages to the lung epithelium in adults without asthma.
PMID- 26439881
TI - Novel viral genomes identified from six metagenomes reveal wide distribution of
archaeal viruses and high viral diversity in terrestrial hot springs.
AB - Limited by culture-dependent methods the number of viruses identified from
thermophilic Archaea and Bacteria is still very small. In this study we retrieved
viral sequences from six hot spring metagenomes isolated worldwide, revealing a
wide distribution of four archaeal viral families, Ampullaviridae,
Bicaudaviridae, Lipothrixviridae and Rudiviridae. Importantly, we identified 10
complete or near complete viral genomes allowing, for the first time, an
assessment of genome conservation and evolution of the Ampullaviridae family as
well as Sulfolobus Monocaudavirus 1 (SMV1)-related viruses. Among the novel
genomes, one belongs to a putative thermophilic virus infecting the bacterium
Hydrogenobaculum, for which no virus has been reported in the literature.
Moreover, a high viral diversity was observed in the metagenomes, especially
among the Lipothrixviridae, as indicated by the large number of unique contigs
and the lack of a completely assembled genome for this family. This is further
supported by the large number of novel genes in the complete and partial genomes
showing no sequence similarities to public databases. CRISPR analysis revealed
hundreds of novel CRISPR loci and thousands of novel CRISPR spacers from each
metagenome, reinforcing the notion of high viral diversity in the thermal
environment.
PMID- 26439882
TI - Tailored Fringed Platforms Produced by Laser Interference for Aligned Neural Cell
Growth.
AB - Ordering neural cells is of interest for the development of neural interfaces.
The aim of this work is to demonstrate an easy-to-use, versatile, and cost/time
effective laser-based approach for producing platforms that promote oriented
neural growth. We use laser interferometry to generate fringed channels with
topography on partially reduced graphene oxide layers as a proof-of-concept
substrate. We study cell adhesion, morphology, viability, and differentiation in
cultures of embryonic neural progenitor cells on platforms with a 9.4 MUm period.
Results evidence that fringed platforms significantly promote neurite alignment
(~50% at 6 d), while preserving viability and neural differentiation.
PMID- 26439883
TI - Effect of Co-solutes on Template-Directed Nonenzymatic Replication of Nucleic
Acids.
AB - The widely acknowledged 'RNA world' theory pertains to how life might have
chemically originated on early Earth. It presumes the existence of catalytic
RNAs, which were also capable of storing and propagating genetic information.
Substantial research has gone into understanding how enzyme-free reactions of
nucleic acids might have led to the formation of such catalytic RNA polymers.
However, most of these studies involved reactions that were performed in aqueous
systems devoid of any "background" molecules. This scenario is not a true
representation of the complex chemical environment that might have been prevalent
on prebiotic Earth. In the present study, we analyzed the effect of co-solutes
("background" molecules) on the rate and accuracy of template-directed
nonenzymatic replication of RNA, in a putative RNA world. Our results suggest
that presence of co-solutes in the reaction affects the addition of purine
monomers across their cognate template base. Reduction in the rate of these
'fast' cognate addition reactions resulted in an apparent increase in the
frequency of mismatches in the presence of co-solutes. However, reactions that
involved the addition of a mismatched base were not notably affected. Such a
scenario could have led to an accrual of mutations during the propagation of
functional sequences on early Earth, unless the relevant sequences were separated
from the bulk reaction milieu by some limiting boundary structure (e.g., a
membrane). In general, our results suggest that the presence of co-solutes could
have affected certain prebiotic reaction rates to a larger extent than others.
Even modest changes in nonenzymatic replication reaction rates could have
eventually resulted in the accumulation of greater variation in RNA sequences
over prolonged time periods. It, therefore, is pertinent to account for the
chemical complexity intrinsic to prebiotic environments while studying relevant
nonenzymatic reactions.
PMID- 26439888
TI - Calcium-Catalyzed Dynamic Multicomponent Reaction.
AB - The reversible formation of covalent bonds enabled by the remarkably high Lewis
acidity of our calcium-based catalyst system was used for the development of a
new type of multicomponent reaction. Accordingly, a pharmacologically interesting
bicyclic amine was amplified from a highly efficient dynamic equilibrium. The
product is formed with full diastereoselectivity, and as typical for our calcium
catalyzed reactions, precautions for the exclusion of air and moisture are
unnecessary.
PMID- 26439887
TI - Antibiotic Stewardship: What's Not To Like?
PMID- 26439884
TI - Unusual Aggregation-Induced Emission of a Coumarin Derivative as a Result of the
Restriction of an Intramolecular Twisting Motion.
AB - Aggregation-induced emission (AIE) is commonly observed for propeller-like
luminogens with aromatic rotors and stators. Herein, we report that a coumarin
derivative containing a seven-membered aliphatic ring (CD-7) but no rotors showed
typical AIE characteristics, whereas its analogue with a five-membered aliphatic
ring (CD-5) exhibited an opposite aggregation-caused quenching (ACQ) effect.
Experimental and theoretical results revealed that a large aliphatic ring in CD-7
weakens structural rigidity and promotes out-of-plane twisting of the molecular
backbone to drastically accelerate nonradiative excited-state decay, thus
resulting in poor emission in solution. The restriction of twisting motion in
aggregates blocks the nonradiative decay channels and enables CD-7 to fluoresce
strongly. The results also show that AIE is a general phenomenon and not peculiar
to propeller-like molecules. The AIE and ACQ effects can be switched readily by
the modulation of molecular rigidity.
PMID- 26439885
TI - Role of atmospheric pressure plasma (APP) in wound healing: APP-induced
antifibrotic process in human dermal fibroblasts.
PMID- 26439886
TI - Safety of Intracavernous Bone Marrow-Mononuclear Cells for Postradical
Prostatectomy Erectile Dysfunction: An Open Dose-Escalation Pilot Study.
AB - Evidence from animal models replicating postradical prostatectomy erectile
dysfunction (pRP-ED) suggests intracavernous injection of bone marrow-mononuclear
cells (BM-MNCs) as a promising treatment approach for pRP-ED. We conducted a
phase 1/2 pilot clinical trial of intracavernous autologous BM-MNC injection to
treat pRP-ED (NCT01089387). Twelve patients with localized prostate cancer and
vasculogenic pRP-ED refractory to maximal medical treatment were divided into
four equal groups treated with escalating BM-MNC doses (2*10(7), 2*10(8),
1*10(9), 2*10(9)). Tolerance was the primary endpoint. Secondary endpoints were
the effects on erectile function and penile vascularization at 6 mo, as assessed
using the International Index of Erectile Function-15 and Erection Hardness Scale
questionnaires, and color duplex Doppler ultrasound. We measured the peak
systolic velocity in cavernous arteries and assessed endothelial function using
the penile nitric oxide release test. No serious side effects occurred. At 6 mo
versus baseline, significant improvements of intercourse satisfaction (6.8+/-3.6,
3.9+/-2.5, p=0.044) and erectile function (17.4+/-8.9, 7.3+/-4.5, p=0.006)
domains of the International Index of Erectile Function-15 and Erection Hardness
Scale (2.6+/-1.1, 1.3+/-0.8, p=0.008) were observed in the total population.
Spontaneous erections showed significantly greater improvement with the higher
doses. Clinical benefits were associated with improvement of peak systolic
velocity and of % penile nitric oxide release test and sustained after 1 yr. Our
results need to be confirmed by phase 2 clinical trials. PATIENT SUMMARY: We
report a phase 1/2 pilot clinical trial investigating cell therapy with injection
of bone marrow mononucleated cells to treat postradical prostatectomy erectile
dysfunction. No serious side effects occurred. Improvements of erectile function
and penile vascularization were noted. Further studies are required to confirm
these preliminary results.
PMID- 26439889
TI - Selective remote C-H sulfonylation of aminoquinolines with arylsulfonyl chlorides
via copper catalysis.
AB - Copper-catalysed direct C-H bond sulfonylation of aminoquinolines using
commercially available and inexpensive arylsulfonyl chlorides as the
sulfonylation reagents is described. The reactions took place exclusively at the
C5-H position of the quinoline rings and tolerated a wide spectrum of functional
groups. Moreover, synthetic transformations of the sulfonylated products led to
useful compounds.
PMID- 26439890
TI - ACR Appropriateness Criteria(r) Intensive Care Unit Patients.
AB - Portable chest radiography is a fundamental and frequently utilized examination
in the critically ill patient population. The chest radiograph often represents a
timely investigation of new or rapidly evolving clinical findings and an
evaluation of proper positioning of support tubes and catheters. Thoughtful
consideration of the use of this simple yet valuable resource is crucial as
medical cost containment becomes even more mandatory. This review addresses the
role of chest radiography in the intensive care unit on the basis of the existing
literature and as formed by a consensus of an expert panel on thoracic imaging
through the American College of Radiology. The American College of Radiology
Appropriateness Criteria are evidence-based guidelines for specific clinical
conditions that are reviewed every 3 years by a multidisciplinary expert panel.
The guideline development and review include an extensive analysis of current
medical literature from peer-reviewed journals and the application of a well
established consensus methodology (modified Delphi) to rate the appropriateness
of imaging and treatment procedures by the panel. In those instances in which
evidence is lacking or not definitive, expert opinion may be used to recommend
imaging or treatment.
PMID- 26439891
TI - Treatment Failure of Active Vitamin D Therapy in Chronic Kidney Disease:
Predictive Factors.
AB - BACKGROUND: In patients with chronic kidney disease (CKD), impaired renal
function leads to decreased vitamin D levels, which causes an increase in
parathyroid hormone (PTH) production and contributes to the development of
secondary hyperparathyroidism (SHPT). This may result in adverse clinical effects
such as bone disorders, vascular calcification, cardiovascular disease, and
increased mortality. Current treatment practices and associated outcomes with
active vitamin D treatment in patients with CKD were reviewed with the objective
to assess parameters (such as PTH and serum calcium levels) that may be used to
define the failure of vitamin D treatment. SUMMARY: Reports based on
observational data have noted improved outcomes with active vitamin D treatment
(calcitriol, paricalcitol, alfacalcidol, or doxercalciferol) in patients with
CKD. Criteria for the identification of active vitamin D treatment failure are
unclear from current guidelines, although up to 50% of patients may experience
treatment failure eventually because of development of hypercalcemia or resistant
SHPT, characterized by an elevated intact PTH (iPTH) level despite treatment. We
propose a definition of vitamin D treatment failure as iPTH >600 pg/ml after 6
months of intravenous active vitamin D treatment and corrected total calcium
serum levels >10.2 mg/dl, and review factors that may predict the response to
vitamin D treatment. Key Message: Active vitamin D treatment failure is an
important challenge in clinical practice. The aim of the proposed definition is
to suggest a possible framework for hypothesis generation and to encourage
further research into this common problem.
PMID- 26439892
TI - An Electrochromic Tristable Molecular Switch.
AB - A tristable [2]catenane, composed of a macrocyclic polyether incorporating 1,5
dioxynaphthalene (DNP) and tetrathiafulvalene (TTF) units along with a 4,4'
bipyridinium (BIPY(*+)) radical cation as three very different potential
recognition sites, interlocked mechanically with the tetracationic cyclophane,
cyclobis(paraquat-p-phenylene) (CBPQT(4+)), was synthesized by donor-acceptor
templation, employing a "threading-followed-by-cyclization" approach. In this
catenane, movement of the CBPQT(4+) ring in its different redox states among
these three potential recognition sites, with corresponding color changes, is
achieved by tuning external redox potentials. In the starting state, where no
external potential is applied, the ring encircles the TTF unit and displays a
green color. Upon oxidation of the TTF unit, the CBPQT(4+) ring moves to the DNP
unit, producing a red color. Finally, if all the BIPY(2+) units are reduced to
BIPY(*+) radical cations, the resulting CBPQT(2(*+)) diradical dication will
migrate to the BIPY(*+) unit, resulting in a purple color. These readily
switchable electrochromic properties render the [2]catenane attractive for use in
electro-optical devices.
PMID- 26439894
TI - Nanoprecipitation and Spectroscopic Characterization of Curcumin-Encapsulated
Polyester Nanoparticles.
AB - Curcumin-encapsulated polyester nanoparticles (Cur-polyester NPs) of
approximately 100 nm diameter with a negatively charged surface were prepared
using a one-step nanoprecipitation method. The Cur-polyester NPs were prepared
using polylactic acid, poly(D,L-lactic-co-glycolic acid) and poly(epsilon
caprolactone) without any emulsifier or surfactant. The encapsulation of curcumin
in these polyester NPs greatly suppresses curcumin degradation in the aqueous
environment due to its segregation from water. In addition, the fluorescence of
curcumin in polyester NPs has a quantum yield of 4 to 5%, which is higher than
that of curcumin in micellar systems and comparable to those in organic solvents,
further supporting the idea that the polyester NPs are capable of excluding water
from curcumin. Furthermore, the results from femtosecond fluorescence
upconversion spectroscopy reveal that there is a decrease in the signal amplitude
corresponding to solvent reorganization of excited state curcumin in the
polyester NPs compared with curcumin in micellar systems. The Cur-polyester NPs
also show a lack of deuterium isotope effect in the fluorescence lifetime. These
results indicate that the interaction between curcumin and water in the polyester
NPs is significantly weaker than that in micelles. Therefore, the aqueous
stability of curcumin is greatly improved due to highly effective segregation
from water. The overall outcome suggests that the polyester NPs prepared using
the method reported herein are an attractive system for encapsulating and
stabilizing curcumin in the aqueous environment.
PMID- 26439895
TI - Toward a Molecular Lego Approach for the Diversity-Oriented Synthesis of
Cyclodextrin Analogues Designed as Scaffolds for Multivalent Systems.
AB - A modular strategy has been developed to access a diversity of cyclic and acyclic
oligosaccharide analogues designed as prefunctionalized scaffolds for the
synthesis of multivalent ligands. This convergent approach is based on
bifunctional sugar building blocks with two temporarily masked functionalities
that can be orthogonally activated to perform Cu(I)-catalyzed azide-alkyne
cycloaddition reactions (CuAAC). The reducing end is activated as a glycosyl
azide and masked as a 1,6-anhydro sugar, while the nonreducing end is activated
as a free alkyne and masked as a triethylsilyl-alkyne. Following a
cyclooligomerization approach, the first examples of close analogues of
cyclodextrins composed of d-glucose residues and triazole units bound together
through alpha-(1,4) linkages were obtained. The cycloglucopyranoside analogue
containing four sugar units was used as a template to prepare multivalent systems
displaying a protected d-mannose derivative or an iminosugar by way of CuAAC. On
the other hand, the modular approach led to acyclic alkyne-functionalized
scaffolds of a controlled size that were used to synthesize multivalent
iminosugars.
PMID- 26439893
TI - Micronutrient status and neurodevelopment in internationally adopted children.
AB - AIM: To assess the status of nutrients relevant for brain development in
internationally adoptees from disparate global regions and determine whether
identified deficiencies are associated with neurodevelopment. METHODS:
Participants included children adopted from Post-Soviet States (n = 15), Ethiopia
(n = 26) or China (n = 17), ages 8-18 months. A comprehensive nutritional battery
and a neurodevelopmental assessment were completed at baseline (within one month
of arrival) and follow-up (six months later). RESULTS: At baseline, 35% were
stunted, and 68% had at least one abnormal nutritional biochemical marker. The
most common were low retinol-binding protein (33%), zinc deficiency (29%),
vitamin D insufficiency/deficiency (21%), and iron deficiency (15%). There was
significant catch-up growth in height and weight at follow-up, but little
improvement in micronutrient deficiencies. Iron deficiency was associated with
lower cognitive scores on the Bayley Scales of Infant Development-III, p = 0.027,
and slower speed of processing, p = 0.012. Zinc deficiency was associated with
compromised memory functioning, p = 0.001. CONCLUSION: Nutrient deficiencies were
common during the early adoption period in internationally adoptees from three
global regions, and iron and zinc deficiencies were associated with poorer
neurodevelopmental outcomes. Results emphasise the importance of monitoring
micronutrient status at arrival and during the early adoption period,
irrespective of country of origin.
PMID- 26439896
TI - Reduction of Foxp3+ T cell subsets involved in incidence of chronic graft-versus
host disease after allogeneic hematopoietic stem cell transplantation.
AB - Foxp3+ T cells (CD4+ Tregs and CD8+ Treg) have been demonstrated to play roles in
the maintenance of tolerance after allogeneic hematopoietic stem cell
transplantation (Allo-HSCT). We have found that Foxp3+ gammadeltaTCR+ Treg cells
(gammadeltaTregs) exerted regulatory functions. In the current study, patients
were recruited and divided as non-cGVHD, limited cGVHD and extensive cGVHD
groups. Healthy volunteers were recruited as healthy group. Treg cells were
evaluated by flow cytometry. Serum cytokine levels of IL-2, tumour necrosis
factor-alpha, interferon-gamma and transforming growth factor-beta1 (TGF-beta1)
were evaluated by ELISA. The results showed that percentages of CD4+ Tregs, CD8+
Tregs and gammadeltaTregs were all significantly increased in non-cGVHD group
compared with those in healthy group, limited cGVHD group and extensive cGVHD
group. Moreover, compared with extensive cGVHD group, percentages of these three
types of Tregs were significantly increased in limited cGVHD group. The levels of
TGF-beta1 increased dramatically in non-cGVHD group compared with other groups.
Spearman's correlation analysis revealed that the increased levels of TGF-beta1
and IL-2 were positively associated with increased Treg subsets, indicating that
TGF-beta1 and IL-2 participated in the expansion process of Foxp3+ Tregs in vivo.
Our findings support that increasing the number of Tregs following allo-HSCT
would be a preferential strategy for controlling cGVHD. Copyright (c) 2015 John
Wiley & Sons, Ltd.
PMID- 26439897
TI - Multifunctional Fluorescent-Magnetic Polymeric Colloidal Particles: Preparations
and Bioanalytical Applications.
AB - Fluorescent-magnetic particles (FMPs) play important roles in modern materials,
especially as nanoscale devices in the biomedical field. The interesting features
of FMPs are attributed to their dual detection ability, i.e., fluorescent and
magnetic modes. Functionalization of FMPs can be performed using several types of
polymers, allowing their use in various applications. The synergistic potentials
for unique multifunctional, multilevel targeting nanoscale devices as well as
combination therapies make them particularly attractive for biomedical
applications. However, the synthesis of FMPs is challenging and must be further
developed. In this review article, we summarized the most recent representative
works on polymer-based FMP systems that have been applied particularly in the
bioanalytical field.
PMID- 26439900
TI - An automated, fast and accurate registration method to link stranded seeds in
permanent prostate implants.
AB - The geometry of a permanent prostate implant varies over time. Seeds can migrate
and edema of the prostate affects the position of seeds. Seed movements directly
influence dosimetry which relates to treatment quality. We present a method that
tracks all individual seeds over time allowing quantification of seed movements.
This linking procedure was tested on transrectal ultrasound (TRUS) and cone-beam
CT (CBCT) datasets of 699 patients. These datasets were acquired intraoperatively
during a dynamic implantation procedure, that combines both imaging modalities.
The procedure was subdivided in four automatic linking steps. (I) The Hungarian
Algorithm was applied to initially link seeds in CBCT and the corresponding TRUS
datasets. (II) Strands were identified and optimized based on curvature and
linefits: non optimal links were removed. (III) The positions of unlinked seeds
were reviewed and were linked to incomplete strands if within curvature- and
distance-thresholds. (IV) Finally, seeds close to strands were linked, also if
the curvature-threshold was violated. After linking the seeds an affine
transformation was applied. The procedure was repeated until the results were
stable or the 6th iteration ended. All results were visually reviewed for
mismatches and uncertainties. Eleven implants showed a mismatch and in 12 cases
an uncertainty was identified. On average the linking procedure took 42 ms per
case. This accurate and fast method has the potential to be used for other time
spans, like Day 30, and other imaging modalities. It can potentially be used
during a dynamic implantation procedure to faster and better evaluate the quality
of the permanent prostate implant.
PMID- 26439899
TI - Performance of interferon-gamma release assay for tuberculosis screening in
inflammatory bowel disease patients: Disease activity as an influencing factor.
PMID- 26439898
TI - Supramolecular Guest-Host Interactions for the Preparation of Biomedical
Materials.
AB - Supramolecular chemistry has emerged as an important technique for the formation
of biomaterials, including nano- and microparticles and hydrogels. One specific
class of supramolecular chemistry is the direct association of guest-host pairs,
which involves host macrocycles such as cyclodextrins and cucurbit[n]urils and a
wide range of guest molecules, where association is typically driven by molecule
size and hydrophobicity. These systems are of particular interest in the
biomedical field due to their dynamic nature, chemical diversity, relative ease
of synthesis, and ability to interact with biological or synthetic molecules. In
this review, we discuss aspects of polymeric material assembly mediated by guest
host interactions, including the fundamentals of assembly into functional
biomedical materials. Additionally, applications of biomaterials that utilize
guest-host interactions are discussed with a focus on injectable material
formulations, the sequestration and delivery of encapsulated cargo (i.e., drugs,
biomolecules), and the investigation of cell-material interactions (i.e.,
adhesion, differentiation, and delivery). While methodologies for guest-host
mediated assembly and biological interaction have rapidly evolved in recent
years, they remain far from realizing their full potential in the biomaterials
field.
PMID- 26439901
TI - Untreated maternal hyperthyroidism responsible of early neonatal demise.
PMID- 26439903
TI - Laterality, sex, and everyday spatial behaviours: an exploratory analysis.
AB - Exploratory analyses of a 126-item self-report assessment of difficulty of
spatial behaviours (revision of the Everyday Spatial Behavioral Questionnaire,
ESBQ) were used to examine principal components and the underlying root structure
of perceived spatial competencies. We also examined laterality measures
(handedness, footedness, and earedness), sex, and age as predictors of spatial
behaviour component scores. 12 principal components were identified that
represented facets of spatial behaviour and perception. Canonical analysis
revealed 2 underlying dimensions of perceived difficulty in performing spatial
behaviours: difficulty with spatial relations in the context of movement and
difficulty with judging how things relate to each other or to a larger surround.
Sex was more closely related to the former dimension; laterality measures and age
were more closely related to the latter. With respect to specific components,
women tended to report more difficulty with making judgements in relation to
earth-fixed axes but less difficulty in judging relations to nearby objects and
how objects fit together or within a surround. Right-handedness was associated
with more perceived difficulty in judging spatial relations while driving,
overlaying surfaces, and moving in relation to other objects in nearby space.
Future confirmatory analyses will be needed to establish subscales of the ESBQ
and their usefulness for practical applications.
PMID- 26439904
TI - Rebuilding the infarcted heart with noncellular material.
PMID- 26439902
TI - IL-1alpha is a DNA damage sensor linking genotoxic stress signaling to sterile
inflammation and innate immunity.
AB - Environmental signals can be translated into chromatin changes, which alter gene
expression. Here we report a novel concept that cells can signal chromatin damage
from the nucleus back to the surrounding tissue through the cytokine interleukin
1alpha (IL-1alpha). Thus, in addition to its role as a danger signal, which
occurs when the cytokine is passively released by cell necrosis, IL-1alpha could
directly sense DNA damage and act as signal for genotoxic stress without loss of
cell integrity. Here we demonstrate localization of the cytokine to DNA-damage
sites and its subsequent secretion. Interestingly, its nucleo-cytosolic shuttling
after DNA damage sensing is regulated by histone deacetylases (HDAC) and IL
1alpha acetylation. To demonstrate the physiological significance of this newly
discovered mechanism, we used IL-1alpha knockout mice and show that IL-1alpha
signaling after UV skin irradiation and DNA damage is important for triggering a
sterile inflammatory cascade in vivo that contributes to efficient tissue repair
and wound healing.
PMID- 26439905
TI - Antitussive, expectorant, and anti-inflammatory activities of four caffeoylquinic
acids isolated from Tussilago farfara.
AB - CONTEXT: The flower bud of Tussilago farfara L. (Compositae) (FTF) is one of the
traditional Chinese medicinal herbs used to treat cough, phlegm, bronchitic, and
asthmatic conditions. OBJECTIVE: The objective of this study is to isolate four
caffeoylquinic acids from the ethyl acetate extract (EtE) of FTF and to evaluate
their antitussive, expectorant, and anti-inflammatory activities. MATERIALS AND
METHODS: The structures of compounds 1-4 isolated from EtE were determined by
spectral analysis. Mice were orally treated with these compounds and their
mixture (in a ratio of 5:28:41:26 as in EtE) at doses of 10 and 20 mg/kg once
daily for 3 d. The antitussive and expectorant activities were evaluated
separately with the ammonia liquor-induced model and the phenol red secretion
model. The anti-inflammation activity was evaluated using leukocyte count in the
bronchoalveolar lavage fluid after ammonia liquor-induced acute airway
inflammation. RESULTS: The four compounds were identified as chlorogenic acid
(1), 3,5-dicaffeoylquinic acid (2), 3,4-dicaffeoylquinic acid (3), and 4,5
dicaffeoylquinic acid (4). All compounds, especially compound 4 (58.0% inhibition
in cough frequency), showed a significant antitussive effect. However, the
mixture was the most effective to inhibit the cough frequency by 61.7%. All
compounds also showed a significant expectorant effect, while compound 2 was the
most potent to enhance the phenol red secretion by 35.7%. All compounds
significantly alleviated inflammation, but compound 4 showed the strongest effect
to inhibit the leukocytosis by 49.7%. DISCUSSION AND CONCLUSION: The
caffeoylquinic acids and their mixture, exhibiting significant antitussive,
expectorant, and anti-inflammatory effects, could be considered as the main
effective ingredients of FTF, and they may act in a collective and synergistic
way.
PMID- 26439906
TI - Self-Assembly of Silver Metal Clusters of Small Atomicity on Cyclic Peptide
Nanotubes.
AB - Subnanometric noble metal clusters, composed by only a few atoms, behave like
molecular entities and display magnetic, luminescent and catalytic activities.
However, noncovalent interactions of molecular metal clusters, lacking of any
ligand or surfactant, have not been seen at work. Theoretically attractive and
experimentally discernible, van der Waals forces and noncovalent interactions at
the metal/organic interfaces will be crucial to understand and develop the next
generation of hybrid nanomaterials. Here, we present experimental and theoretical
evidence of noncovalent interactions between subnanometric metal (0) silver
clusters and aromatic rings and their application in the preparation of 1D self
assembled hybrid architectures with ditopic peptide nanotubes. Atomic force
microscopy, fluorescence experiments, circular dichroism and computational
simulations verified the occurrence of these interactions in the clean and mild
formation of a novel peptide nanotube and metal cluster hybrid material. The
findings reported here confirmed the sensitivity of silver metal clusters of
small atomicity toward noncovalent interactions, a concept that could find
multiple applications in nanotechnology. We conclude that induced supramolecular
forces are optimal candidates for the precise spatial positioning and properties
modulation of molecular metal clusters. The reported results herein outline and
generalize the possibilities that noncovalent interactions will have in this
emerging field.
PMID- 26439908
TI - Association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism
with preterm delivery and placental abruption: a systematic review and meta
analysis.
AB - INTRODUCTION: The aim of this study was to summarize evidence on the association
between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and odds
of preterm delivery and placental abruption. MATERIAL AND METHODS: PubMed,
EMBASE, CBM (Chinese Biomedical Database) and CNKI (Chinese National Knowledge
Infrastructure) were searched to identify eligible studies published in English
or Chinese before 12 August 2014. The pooled odds ratios (ORs) with 95%
confidence intervals were estimated for the association of MTHFR C677T
polymorphism with preterm delivery and placental abruption using random effects
models. RESULTS: A total of 22 studies that met inclusion and exclusion criteria
were included in this meta-analysis. Regardless of the genetic model tested we
found no statistically significant association of MTHFR C677T polymorphism with
preterm delivery or placental abruption. Funnel plots inspections, Begg's test
and Egger's test did not show evidence of publication bias. CONCLUSIONS: This
meta-analysis demonstrated that overall there was no association of MTHFR C677T
polymorphism with preterm delivery or placental abruption.
PMID- 26439907
TI - Clostridium difficile recurrent infection: possible implication of TA systems.
AB - Clostridium difficile is an important nosocomial pathogen associated with
antibiotic treatments. C. difficile's ability to survive antimicrobial therapy
and transition from inert colonization to active infection is one of the most
perplexing aspects of C. difficile infections and suggests that additional
mechanisms are involved in persistence. In this regard, novel mechanisms linked
with pathogenesis and persistence of C. difficile such as toxin-antitoxin systems
might significantly contribute to biofilm formation and persistent infection.
This review will focus on advances of toxin-antitoxin systems in C. difficile and
their putative roles will be discussed.
PMID- 26439911
TI - A brief review of the application and pharmacology of ethnomedicines of
Indigenous Australians.
AB - OBJECTIVE: Indigenous Australians suffer higher mortality and have statistically
worse outcomes for many chronic disease states than the non-Indigenous
population. Although many of these people are prescribed pharmaceutical drugs for
their illnesses, some still use medicines that were traditional to their culture.
This report reviews some of the traditional medicines used for ailments seen in
Indigenous Australian communities. DESIGN: A literature search was conducted,
with the period between the publication of an 'Aboriginal Pharmacopoeia' in 1988
and 'current' our target interval for searching. The ethics of publishing
knowledge belonging to Aboriginal people is briefly discussed in this context.
RESULTS: Ailments were grouped into communicable diseases, pain and inflammation,
skin disorders and gastrointestinal disorders. Although cancer is regarded as a
disease of the 'white man', it is briefly discussed in the context that several
traditional medicines and foods may have provided some protective effects. Where
known, the ethnopharmacology of these medicines is discussed, as well as a brief
description of their preparation and application. CONCLUSION: Some Indigenous
Australians continue to use traditional medicines. We have tabulated these
according to ailment, and have listed pharmacological actions where known. What
is not known, however, is their potential to interact with pharmaceutical drugs.
Further study in this area is needed to optimise health outcomes for Indigenous
Australians, especially those in remote communities.
PMID- 26439910
TI - [Quality of life as a function of treatment in black patients with primary open
angle glaucoma].
PMID- 26439912
TI - Corrigendum.
PMID- 26439913
TI - Mechanism for the stabilization of protein clusters above the solubility curve.
AB - Pan, Vekilov and Lubchenko [J. Phys. Chem. B, 2010, 114, 7620] have proposed that
dense stable protein clusters appearing in weak protein solutions above the
solubility curve are composed of protein oligomers. The hypothesis is that a weak
solution of oligomer species is unstable with respect to condensation causing the
formation of dense, oligomer-rich droplets which are stabilized against growth by
the monomer-oligomer reaction. Here, we show that such a combination of processes
can be understood using a simple capillary model yielding analytic expressions
for the cluster properties which can be used to interpret experimental data. We
also construct a microscopic Dynamic Density Functional Theory model and show
that it is consistent with the predictions of the capillary model. The viability
of the mechanism is thus confirmed and it is shown how the radius of the stable
clusters is related to physically interesting quantities such as the monomer
oligomer rate constants.
PMID- 26439916
TI - Thermal surface free energy and stress of iron.
AB - Absolute values of surface energy and surface stress of solids are hardly
accessible by experiment. Here, we investigate the temperature dependence of both
parameters for the (001) and (110) surface facets of body-centered cubic Fe from
first-principles modeling taking into account vibrational, electronic, and
magnetic degrees of freedom. The monotonic decrease of the surface energies of
both facets with increasing temperature is mostly due to lattice vibrations and
magnetic disorder. The surface stresses exhibit nonmonotonic behaviors resulting
in a strongly temperature dependent excess surface stress and surface stress
anisotropy.
PMID- 26439909
TI - Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor
KIR3DL1 on natural killer cells.
AB - Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen
(HLA) class I ligands and play a key role in the regulation and activation of NK
cells. The functional importance of KIR-HLA interactions has been demonstrated
for a number of chronic viral infections, but to date only a few studies have
been performed in the context of acute self-limited viral infections. During our
investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted
epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we
observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes
in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort
in Thailand. We confirmed binding of the NS1 tetramer to CD56(dim) NK cells,
which are known to express KIRs. Using depletion studies and KIR-transfected cell
lines, we demonstrated further that the NS1 tetramer bound the inhibitory
receptor KIR3DL1. Phenotypical analysis of PBMC from HLA-B57(+) subjects with
acute DENV infection revealed marked activation of NS1 tetramer-binding natural
killer (NK) cells around the time of defervescence in subjects with severe dengue
disease. Collectively, our findings indicate that subsets of NK cells are
activated relatively late in the course of acute DENV illness and reveal a
possible role for specific KIR-HLA interactions in the modulation of disease
outcomes.
PMID- 26439914
TI - Nanometer-size hard magnetic ferrite exhibiting high optical-transparency and
nonlinear optical-magnetoelectric effect.
AB - Development of nanometer-sized magnetic particles exhibiting a large coercive
field (Hc) is in high demand for densification of magnetic recording. Herein, we
report a single-nanosize (i.e., less than ten nanometers across) hard magnetic
ferrite. This magnetic ferrite is composed of epsilon-Fe2O3, with a sufficiently
high Hc value for magnetic recording systems and a remarkably high magnetic
anisotropy constant of 7.7 * 10(6) erg cm(-3). For example, 8.2-nm nanoparticles
have an Hc value of 5.2 kOe at room temperature. A colloidal solution of these
nanoparticles possesses a light orange color due to a wide band gap of 2.9 eV
(430 nm), indicating a possibility of transparent magnetic pigments.
Additionally, we have observed magnetization-induced second harmonic generation
(MSHG). The nonlinear optical-magnetoelectric effect of the present polar
magnetic nanocrystal was quite strong. These findings have been demonstrated in a
simple iron oxide, which is highly significant from the viewpoints of economic
cost and mass production.
PMID- 26439918
TI - Prevalence of peripheral nervous system complications after major heart surgery.
AB - We evaluated 374 consecutive patients from May 2013 to April 2014 who underwent
major cardiac surgery. Each patient had an interview and a neurological clinical
examination during the rehabilitation period. Patients with possible peripheral
nervous system (PNS) complications underwent further electrodiagnostic tests.
Among 374 patients undergoing major heart surgery (coronary artery bypass
grafting, valvular heart surgery, ascending aortic aneurysm repair) 23 (6.1 %)
developed 34 new PNS complications. We found four brachial plexopathies; four
carpal tunnel syndromes; five critical illness neuropathies; three worsening of
pre-existing neuropathies; two involvement of X, one of IX and one of XII cranial
nerves; three peroneal (at knee), one saphenous, two median (at Struthers
ligament), six ulnar (at elbow) mononeuropathies; two meralgia parestheticas.
Diabetes is a strong risk factor for PNS complications (p = 0.002); we could not
find any other relationship of PNS complications with clinical conditions,
demographic data (gender, age) or type of surgical intervention. The
mononeuropathies of right arms can be related to ipsilateral vein cannulation;
position of body and stretching from chest wall retraction may be the cause of
mononeuropathies of left arms (more frequent); the use of saphenous vein and
position of the limbs may be the cause of mononeuropathies of the legs; surgical
and anesthetical procedures can injure cranial nerves; respiratory failure and
infection during the first days after surgery can cause critical illness
neuropathies. Careful preoperative assessment and intraoperative management may
reduce the risk of long-term PNS complications after cardiac surgery.
PMID- 26439919
TI - The management of multiple sclerosis by reference centers in south of Italy: a
2011 survey on health demands and needs in Campania region.
AB - This cross-sectional study has investigated the diagnostic and therapeutic
management of patients suffering from multiple sclerosis (MS) in the Campania
Region (Italy). A survey involving all the reference centers for MS in Campania
Region was conducted from March to August 2011. Centers responded to a web
administered questionnaire on management and clinical characteristics of MS
patients. In the study period, 3263 patients (mean age 37 years, 66 % females)
accessed the centers. Patients received a first diagnosis of MS in 161 cases (4.9
%). About 37 % of the subjects without a previous diagnosis came to the centers
on their own initiative. All patients underwent a complete neurological
examination and expanded disability status scale. The other most common
investigations were magnetic resonance imaging (44.0 %) and evoked potentials
(22.1 %). The number of treated patients was 2797 (87.1 %). The most used drugs
were interferon beta and glatiramer acetate. The time between diagnosis and
initiation of therapy exceeded 6 months in 32 % of cases. Second-line drugs were
under-used: 16 % of patients who might benefit from them show high clinical and
radiological disease activity despite treatment with immunomodulant drugs. The MS
care management of the surveyed centers showed consistent margins for improvement
in 2011. Even though these data do not represent the current situation, they can
be used to monitor improvements in MS care.
PMID- 26439917
TI - Cell Phone-Based and Adherence Device Technologies for HIV Care and Treatment in
Resource-Limited Settings: Recent Advances.
AB - Numerous cell phone-based and adherence monitoring technologies have been
developed to address barriers to effective HIV prevention, testing, and
treatment. Because most people living with HIV and AIDS reside in resource
limited settings (RLS), it is important to understand the development and use of
these technologies in RLS. Recent research on cell phone-based technologies has
focused on HIV education, linkage to and retention in care, disease tracking, and
antiretroviral therapy adherence reminders. Advances in adherence devices have
focused on real-time adherence monitors, which have been used for both
antiretroviral therapy and pre-exposure prophylaxis. Real-time monitoring has
recently been combined with cell phone-based technologies to create real-time
adherence interventions using short message service (SMS). New developments in
adherence technologies are exploring ingestion monitoring and metabolite
detection to confirm adherence. This article provides an overview of recent
advances in these two families of technologies and includes research on their
acceptability and cost-effectiveness when available. It additionally outlines key
challenges and needed research as use of these technologies continues to expand
and evolve.
PMID- 26439915
TI - Neonicotinoid Residues in Wildflowers, a Potential Route of Chronic Exposure for
Bees.
AB - In recent years, an intense debate about the environmental risks posed by
neonicotinoids, a group of widely used, neurotoxic insecticides, has been joined.
When these systemic compounds are applied to seeds, low concentrations are
subsequently found in the nectar and pollen of the crop, which are then collected
and consumed by bees. Here we demonstrate that the current focus on exposure to
pesticides via the crop overlooks an important factor: throughout spring and
summer, mixtures of neonicotinoids are also found in the pollen and nectar of
wildflowers growing in arable field margins, at concentrations that are sometimes
even higher than those found in the crop. Indeed, the large majority (97%) of
neonicotinoids brought back in pollen to honey bee hives in arable landscapes was
from wildflowers, not crops. Both previous and ongoing field studies have been
based on the premise that exposure to neonicotinoids would occur only during the
blooming period of flowering crops and that it may be diluted by bees also
foraging on untreated wildflowers. Here, we show that exposure is likely to be
higher and more prolonged than currently recognized because of widespread
contamination of wild plants growing near treated crops.
PMID- 26439920
TI - The Mini Report: a Practical Tool to Address Lung Cancer Disparities in Rural
Communities.
AB - Community-based participatory research (CBPR) is an effective way to address
cancer disparities in medically underserved populations. Our research
demonstrates how CBPR principles were used to develop lung cancer and risk factor
mini reports for a network of community coalitions in the Illinois Delta Region,
a predominately rural region with high lung cancer disparities in southern
Illinois. An academic-community partnership, including a community-based medical
school, state public health department, and a healthcare system, used CBPR
principles to translate epidemiological, behavioral, and demographic data into
understandable, comprehensive, yet concise mini reports for each coalition. A
cyclical and iterative process was used to draft, revise, and optimize these mini
reports to raise awareness about lung cancer disparities in the community and to
provide information to help guide the development of interventions that address
these disparities. The use of CBPR principles was a successful way to create mini
reports about local lung cancer disparities and risk factors that were usable in
individual communities. Local coalitions used the mini reports to educate
community members at local meetings, to guide strategic planning, and to
disseminate information through their respective websites. Additionally, the
process of creating these reports built trust among academic-community partners
and provided additional avenues of engagement, such as the involvement of an
academic partner in the strategic planning process of a local coalition. Using
CBPR processes is an effective way to translate epidemiological data into a
community-friendly format to address cancer disparities.
PMID- 26439922
TI - Effects of Physical and Emotional Child Abuse and Its Chronicity on Crime Into
Adulthood.
AB - Analyses tested hypotheses that pertain to direct and indirect effects of parent
reported physical and emotional abuse on later self-reported criminal behavior in
a sample of 356 adults of a longitudinal study of more than 30 years. Childhood
antisocial behavior was included in analyses as a potential mediator. Physical
abuse only predicted adult crime indirectly through childhood antisocial
behavior, whereas emotional abuse predicted adult outcome both directly and
indirectly. Chronicity of physical abuse was indirectly related to later crime in
a subsample test for those who had been physically abused (n=318), whereas
chronicity of emotional abuse was neither directly nor indirectly related to
adult crime in a test of those who had been emotionally abused (n=225).
Implications for future research and practice are discussed.
PMID- 26439924
TI - Correction: Derivation of Soil Ecological Criteria for Copper in Chinese Soils.
PMID- 26439923
TI - Targeted Next-Generation Sequencing Revealed Novel Mutations in Chinese Ataxia
Telangiectasia Patients: A Precision Medicine Perspective.
AB - Ataxia telangiectasia (AT) is an autosomal recessive disease characterized by
progressive cerebellar ataxia, oculocutaneous telangiectasia and immunodeficiency
due to mutations in the ATM gene. We performed targeted next-generation
sequencing (NGS) on three unrelated patients and identified five disease-causing
variants in three probands, including two pairs of heterozygous variants (FAT
1:c.4396C>T/p.R1466X, c.1608-2A>G; FAT-2:c.4412_4413insT/p.L1472Ffs*19,
c.8824C>T/p.Q2942X) and one pair of homozygous variants (FAT-3:
c.8110T>G/p.C2704G, Hom). With regard to precision medicine for rare genetic
diseases, targeted NGS currently enables the rapid and cost-effective
identification of causative mutations and is an updated molecular diagnostic tool
that merits further optimization. This high-throughput data-based strategy would
propel the development of precision diagnostic methods and establish a foundation
for precision medicine.
PMID- 26439921
TI - Uncovering Hidden Layers of Cell Cycle Regulation through Integrative Multi-omic
Analysis.
AB - Studying the complex relationship between transcription, translation and protein
degradation is essential to our understanding of biological processes in health
and disease. The limited correlations observed between mRNA and protein abundance
suggest pervasive regulation of post-transcriptional steps and support the
importance of profiling mRNA levels in parallel to protein synthesis and
degradation rates. In this work, we applied an integrative multi-omic approach to
study gene expression along the mammalian cell cycle through side-by-side
analysis of mRNA, translation and protein levels. Our analysis sheds new light on
the significant contribution of both protein synthesis and degradation to the
variance in protein expression. Furthermore, we find that translation regulation
plays an important role at S-phase, while progression through mitosis is
predominantly controlled by changes in either mRNA levels or protein stability.
Specific molecular functions are found to be co-regulated and share similar
patterns of mRNA, translation and protein expression along the cell cycle.
Notably, these include genes and entire pathways not previously implicated in
cell cycle progression, demonstrating the potential of this approach to identify
novel regulatory mechanisms beyond those revealed by traditional expression
profiling. Through this three-level analysis, we characterize different
mechanisms of gene expression, discover new cycling gene products and highlight
the importance and utility of combining datasets generated using different
techniques that monitor distinct steps of gene expression.
PMID- 26439927
TI - Probing local pH-based precipitation processes in self-assembled silica-carbonate
hybrid materials.
AB - Crystallisation of barium carbonate in the presence of silica can lead to the
spontaneous assembly of highly complex superstructures, consisting of uniform and
largely co-oriented BaCO3 nanocrystals that are interspersed by a matrix of
amorphous silica. The formation of these biomimetic architectures (so-called
silica biomorphs) is thought to be driven by a dynamic interplay between the
components, in which subtle changes of conditions trigger ordered mineralisation
at the nanoscale. In particular, it has been proposed that local pH gradients at
growing fronts play a crucial role in the process of morphogenesis. In the
present work, we have used a special pH-sensitive fluorescent dye to directly
trace these presumed local fluctuations by means of confocal laser scanning
microscopy. Our data demonstrate the existence of an active region near the
growth front, where the pH is locally decreased with respect to the alkaline bulk
solution on a length scale of few microns. This observation provides fundamental
and, for the first time, direct experimental support for the current picture of
the mechanism underlying the formation of these peculiar materials. On the other
hand, the absence of any temporal oscillations in the local pH - another key
feature of the envisaged mechanism - challenges the notion of autocatalytic
phenomena in such systems and raises new questions about the actual role of
silica as an additive in the crystallisation process.
PMID- 26439925
TI - Retracted article: In vitro derivation of mammalian germ cells from stem cells
and their potential therapeutic application.
AB - Pluripotent stem cells (PSCs) are a unique type of cells because they exhibit the
characteristics of self-renewal and pluripotency. PSCs may be induced to
differentiate into any cell type, even male and female germ cells, suggesting
their potential as novel cell-based therapeutic treatment for infertility
problems. Spermatogenesis is an intricate biological process that starts from
self-renewal of spermatogonial stem cells (SSCs) and leads to differentiated
haploid spermatozoa. Errors at any stage in spermatogenesis may result in male
infertility. During the past decade, much progress has been made in the
derivation of male germ cells from various types of progenitor stem cells.
Currently, there are two main approaches for the derivation of functional germ
cells from PSCs, either the induction of in vitro differentiation to produce
haploid cell products, or combination of in vitro differentiation and in vivo
transplantation. The production of mature and fertile spermatozoa from stem cells
might provide an unlimited source of autologous gametes for treatment of male
infertility. Here, we discuss the current state of the art regarding the
differentiation potential of SSCs, embryonic stem cells, and induced pluripotent
stem cells to produce functional male germ cells. We also discuss the possible
use of livestock-derived PSCs as a novel option for animal reproduction and
infertility treatment.
PMID- 26439926
TI - Anchors as Semantic Primes in Value Construction: An EEG Study of the Anchoring
Effect.
AB - Previous research regarding anchoring effects has demonstrated that human
judgments are often assimilated to irrelevant information. Studies have
demonstrated that anchors influence the economic valuation of various products
and experiences; however, the cognitive explanations of this effect remain
controversial, and its neural mechanisms have rarely been explored. In the
current study, we conducted an electroencephalography (EEG) experiment to
investigate the anchoring effect on willingness to accept (WTA) for an aversive
hedonic experience and the role of anchors in this judgment heuristic. The
behavioral results demonstrated that random numbers affect participants' WTA for
listening to pieces of noise. The participants asked for higher pay after
comparing their WTA with higher numbers. The EEG results indicated that anchors
also influenced the neural underpinnings of the valuation process. Specifically,
when a higher anchor number was drawn, larger P2 and late positive potential
amplitudes were elicited, reflecting the anticipation of more intensive pain from
the subsequent noise. Moreover, higher anchors induced a stronger theta band
power increase compared with lower anchors when subjects listened to the noises,
indicating that the participants felt more unpleasant during the actual
experience of the noise. The levels of unpleasantness during both anticipation
and experience were consistent with the semantic information implied by the
anchors. Therefore, these data suggest that a semantic priming process underlies
the anchoring effect in WTA. This study provides proof for the robustness of the
anchoring effect and neural evidence of the semantic priming model. Our findings
indicate that activated contextual information, even seemingly irrelevant, can be
embedded in the construction of economic value in the brain.
PMID- 26439928
TI - Simulating Crop Evapotranspiration Response under Different Planting Scenarios by
Modified SWAT Model in an Irrigation District, Northwest China.
AB - Modelling crop evapotranspiration (ET) response to different planting scenarios
in an irrigation district plays a significant role in optimizing crop planting
patterns, resolving agricultural water scarcity and facilitating the sustainable
use of water resources. In this study, the SWAT model was improved by
transforming the evapotranspiration module. Then, the improved model was applied
in Qingyuan Irrigation District of northwest China as a case study. Land use,
soil, meteorology, irrigation scheduling and crop coefficient were considered as
input data, and the irrigation district was divided into subdivisions based on
the DEM and local canal systems. On the basis of model calibration and
verification, the improved model showed better simulation efficiency than did the
original model. Therefore, the improved model was used to simulate the crop
evapotranspiration response under different planting scenarios in the irrigation
district. Results indicated that crop evapotranspiration decreased by 2.94% and
6.01% under the scenarios of reducing the planting proportion of spring wheat
(scenario 1) and summer maize (scenario 2) by keeping the total cultivated area
unchanged. However, the total net output values presented an opposite trend under
different scenarios. The values decreased by 3.28% under scenario 1, while it
increased by 7.79% under scenario 2, compared with the current situation. This
study presents a novel method to estimate crop evapotranspiration response under
different planting scenarios using the SWAT model, and makes recommendations for
strategic agricultural water management planning for the rational utilization of
water resources and development of local economy by studying the impact of
planting scenario changes on crop evapotranspiration and output values in the
irrigation district of northwest China.
PMID- 26439929
TI - PSMB4 expression associates with epithelial ovarian cancer growth and poor
prognosis.
AB - PURPOSE: In this study, we investigated the expression and role of PSMB4 in human
epithelial ovarian cancer(EOC). METHODS: Western blot was used to evaluate the
expression of PSMB4 in EOC tissues, and immunohistochemical analysis was
performed on 115 cases of ovarian cancers. Then, we used Fisher exact test to
analyze the correlation between PSMB4 and clinicopathological parameters.
Starvation and re-feeding assay was used to assess cell cycle. CCK-8 assay and
plate colony formation assay showed the influence of PSMB4 on proliferation of
EOC cells. RESULTS: The expression of PSMB4 in EOC tissues was higher than normal
ovary tissues and was significantly associated with clinical pathologic
variables. Kaplan-Meier curve showed that high expression of PSMB4 was related to
poor prognosis of EOC patients. Starvation and re-feeding assay suggested that
PSMB4 played a critical role in EOC cell proliferation. CCK-8 assay and plate
colony formation assay showed that EOC cells treated with PSMB4-siRNA reduced
cell proliferation of EOC cells. Additionally, PSMB4 knockdown decreased NF
kappaB activity. PSMB4 also regulated the expression of NF-kappaB mediated
proteins, including cyclin D1, and cyclin E which involved in cell proliferation.
CONCLUSIONS: Our findings implied that PSMB4 is involved in the progression of
EOC and could serve as potential therapeutical target of EOC. These data
suggested that PSMB4 may promote cell proliferation via the NF-kappaB-target gene
in EOC.
PMID- 26439931
TI - Influence of Solvation and Structural Contributions on Fluorescence of Dipyrrine
Dyes.
AB - The results of quantum-chemical and spectral researches of zinc((II)) complexes
with alkylated dipyrrine and 3,3'-, 2,3'- and 2,2'-bis(dipyrrine)s in non-polar
and polar solvents and their binary mixtures are presented. It was investigated
the efficiency of the fluorescence quenching of fluorophores depending on of the
solvation and structural contributions. Found that 3,3'
bis(dipyrrinato)zinc((II)) demonstrates the highest sensitivity of the
fluorescence to the presence of the electron-donor component compared with the
studied complexes. The obtained results allow to offer dipyrrine and
bis(dipyrrine) zinc((II)) complexes as new, highly sensitive and selective
fluorescent sensors of the N- and O-containing toxicants. Graphical Abstract
Influence of solvation and structural contributions on fluorescence of dipyrrine
dyes.
PMID- 26439930
TI - Determination of Some Non-sedating Antihistamines via Their Native Fluorescence
and Derivation of Some Quantitative Fluorescence Intensity - Structure
Relationships.
AB - A validated simple, novel, and rapid spectrofluorimetric method was developed for
the determination of some non-sedating antihistamines (NSAs); namely cetirizine
(CTZ), ebastine (EBS), fexofenadine (FXD), and loratadine (LOR). The method is
based on measuring the native fluorescence of the cited drugs after protonation
in acidic media and studying their quantitative fluorescence intensity -
structure relationships. There was a linear relationship between the relative
fluorescence intensity and the concentration of the investigated drug. Under the
optimal conditions, the linear ranges of calibration curves for the determination
of the studied NSAs were 0.10-2.0, 0.20-6.0, and 0.02-1.0 [Formula: see text] for
(CTZ, FXD), (EBS), and (LOR); respectively. The factors affecting the protonation
of the studied drugs were carefully studied and optimized. The method was
validated according to ICH guidelines. The suggested method is applicable for the
determination of the four investigated drugs in bulk and pharmaceutical dosage
forms with excellent recoveries (97.67-103.80%). Quantitative relationships were
found between the relative fluorescence intensities of the protonated drugs and
their physicochemical parameters namely: the pKa, log P, connectivity indexes
(chi(v)) and their squares. Regression equations (76) were obtained and not
previously reported. Six of these equations were highly significant and used for
the prediction of RFI of the studied NSAs.
PMID- 26439932
TI - The Chiropractic Care of Infants with Breastfeeding Difficulties.
AB - OBJECTIVE: Chiropractors have long advocated on the benefits of breastfeeding and
given the realized and potential role of chiropractors in the care of infants
with breastfeeding difficulties, we performed this review of the literature on
the subject to inform clinical practice. METHODS: For this article, we searched
Pubmed [1966-2013], Manual, Alternative and Natural Therapy Index System (MANTIS)
[1964-2013] and Index to Chiropractic Literature [1984-2013] for the relevant
literature. The search terms utilized "breastfeeding", "breast feeding",
"breastfeeding difficulties", "breastfeeding difficulty", "TMJ dysfunction",
"temporomandibular joint", "birth trauma" and "infants", in the appropriate
Boolean combinations. We also examined non-peer-reviewed articles as revealed by
Index to Chiropractic Literature and secondary analysis of references. Inclusion
criteria for review included breastfeeding difficulties regardless of peer-review
and written in the English language. RESULTS: A total of 24 articles met our
inclusion criteria. These consisted of 8 case reports, 2 case series, and 3
cohort studies. We were also able to identify 6 manuscripts (5 case reports and a
case series) that involved breastfeeding difficulties as a secondary complaint.
Our findings reveal a theoretical and clinical framework based on the detection
of spinal and extraspinal subluxations involving the cervico-cranio-mandibular
complex and assessment of the infant while breastfeeding. CONCLUSIONS:
Chiropractors care of infants with breastfeeding difficulties by addressing
spinal and extraspinal subluxations involving the cervico-cranio-mandibular
complex.
PMID- 26439933
TI - Spin-dependent recombination probed through the dielectric polarizability.
AB - Despite residing in an energetically and structurally disordered landscape, the
spin degree of freedom remains a robust quantity in organic semiconductor
materials due to the weak coupling of spin and orbital states. This enforces spin
selectivity in recombination processes which plays a crucial role in
optoelectronic devices, for example, in the spin-dependent recombination of
weakly bound electron-hole pairs, or charge-transfer states, which form in a
photovoltaic blend. Here, we implement a detection scheme to probe the spin
selective recombination of these states through changes in their dielectric
polarizability under magnetic resonance. Using this technique, we access a regime
in which the usual mixing of spin-singlet and spin-triplet states due to
hyperfine fields is suppressed by microwave driving. We present a quantitative
model for this behaviour which allows us to estimate the spin-dependent
recombination rate, and draw parallels with the Majorana-Brossel resonances
observed in atomic physics experiments.
PMID- 26439934
TI - Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum
Triglyceride Levels.
AB - Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding
protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1
levels are associated with an increased risk of cardiovascular disease (CVD) and
metabolic syndromes. In this study, we examine the association of FABP1 gene
promoter variants with serum FABP1 and lipid levels in a Chinese population. Four
promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a
cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of
China. Results showed that only the rs2919872 G>A variant was significantly
associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G
allele, rs2919872 A allele contributed significantly to reduced serum TG
concentration, and this allele dramatically decreased the FABP1 promoter
activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum
FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear
regression analysis, the rs2919872 A allele was negatively associated with serum
FABP1 levels (beta = -0.320, P = 0.003), while serum TG levels were positively
associated with serum FABP1 levels (beta = 0.487, P = 0.014). Our data suggest
that compared with the rs2919872 G allele, the rs2919872 A allele reduces the
transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene
variation to TG level in humans.
PMID- 26439937
TI - Recasting the Callaway and von Baeyer thermal conductivity model on defective
oxide materials: the ZnO-In2O3 system as an example.
AB - Point defects and nanoscale interfaces effectively scatter short and mid-to-long
wavelength phonons, respectively, thereby considerably reducing the thermal
conductivity. In this paper, a classical physical model of phonon transport and
scattering, the Callaway and von Bayer method, is recast with the introduction of
the phonon mean free path cut-off, or equivalently, the minimum phonon relaxation
time. To illustrate the method, we compute the thermal conductivity for the ZnO
In2O3 binary system in which the compositionally dependent structure is
available, including solid solutions consisting of point defects and natural
superlattices. The calculated thermal conductivity is in good agreement with the
experimental measurements, and suggests a threshold value of about 50 nm for the
interface spacing, above which the thermal conductivity becomes less sensitive to
the interfaces with increasing temperature. A useful design clue is implied for
the nanostructural engineering of high temperature thermoelectrics and thermal
barrier coatings.
PMID- 26439935
TI - Accuracy of QuantiFERON-TB Gold Test for Tuberculosis Diagnosis in Children.
AB - OBJECTIVES: To evaluate the accuracy of the QuantiFERON-TB Gold assay (QFT-IT) in
children with suspected active or latent TB infection (LTBI). METHODS: A
retrospective study was conducted on 621 children (0-14 years old) evaluated for
TB infection or disease. Following clinical assessment, children were tested with
the QFT-IT assay. RESULTS: Among the 140 active TB suspects, we identified 19
cases of active disease. The overall sensitivity for active TB was 87.5%, ranging
from 62.5% in children 25-36 months old to 100% in children older than 49 months.
The overall specificity for active TB was 93.6%. Among the 481 children tested
for LTBI screening, 38 scored positive and all but 2 had at least one risk factor
for TB infection. Among the 26 children with indeterminate results, bacterial,
viral or fungal pneumonia were later diagnosed in 11 (42.3%) cases and non-TB
related extra-pulmonary infections in 12 (46.1%). CONCLUSIONS: Our results
indicate that the children's response to QFT-IT associates to active TB and risk
factors for LTBI. Moreover, we show that mitogen response is also found in
children of 1 year of age, providing support for QFT-IT use also in young
children.
PMID- 26439936
TI - Safety Profile of the Use of Iodopovidone for Pleurodesis in Patients with
Malignant Pleural Effusion.
AB - BACKGROUND: Iodopovidone is an alternative agent used to promote pleurodesis in
patients with malignant pleural effusion (MPE). However, safety is a concern, and
many authors still reject its use. OBJECTIVES: Our main objective is to describe
the occurrence of common and severe adverse events after pleurodesis with two
different doses of iodopovidone in patients with MPE. Our secondary objective is
to evaluate dose dependency, efficacy, quality of life, and systemic
inflammation. METHODS: We conducted a double-blind, randomized clinical trial
including patients with recurrent MPE. Patients underwent chest tube insertion
and were randomized into two groups according to the doses of iodopovidone: group
1 received 1% iodopovidone, and group 2 received 2% iodopovidone. During follow
up, adverse events, inflammatory markers, quality of life, and imaging exams were
systematically evaluated and registered. RESULTS: Sixty patients were analyzed
(55 females, 5 males, median age 55.9 years). Overall, 227 adverse events
possibly related to pleurodesis were registered, including 47 serious adverse
events (in 34 patients). Pleuritic pain and hypertensive peaks were the most
frequently observed serious adverse events (11 and 10 episodes, respectively).
Grade 3/4 metabolic events such as hyponatremia and an increase in alkaline
phosphatase, AST and ALT levels were also common. C-reactive protein (CRP) levels
increased substantially and peaked 48 h after pleurodesis. No difference was
observed between groups with regard to adverse events, CRP levels, efficacy, or
quality of life. CONCLUSIONS: Adverse events after iodopovidone pleurodesis in
patients with MPE are common and similar in the two doses studied.
PMID- 26439938
TI - Locally-constrained boundary regression for segmentation of prostate and rectum
in the planning CT images.
AB - Automatic and accurate segmentation of the prostate and rectum in planning CT
images is a challenging task due to low image contrast, unpredictable organ
(relative) position, and uncertain existence of bowel gas across different
patients. Recently, regression forest was adopted for organ deformable
segmentation on 2D medical images by training one landmark detector for each
point on the shape model. However, it seems impractical for regression forest to
guide 3D deformable segmentation as a landmark detector, due to large number of
vertices in the 3D shape model as well as the difficulty in building accurate 3D
vertex correspondence for each landmark detector. In this paper, we propose a
novel boundary detection method by exploiting the power of regression forest for
prostate and rectum segmentation. The contributions of this paper are as follows:
(1) we introduce regression forest as a local boundary regressor to vote the
entire boundary of a target organ, which avoids training a large number of
landmark detectors and building an accurate 3D vertex correspondence for each
landmark detector; (2) an auto-context model is integrated with regression forest
to improve the accuracy of the boundary regression; (3) we further combine a
deformable segmentation method with the proposed local boundary regressor for the
final organ segmentation by integrating organ shape priors. Our method is
evaluated on a planning CT image dataset with 70 images from 70 different
patients. The experimental results show that our proposed boundary regression
method outperforms the conventional boundary classification method in guiding the
deformable model for prostate and rectum segmentations. Compared with other state
of-the-art methods, our method also shows a competitive performance.
PMID- 26439939
TI - Tamarind seed coat ameliorates fluoride induced cytotoxicity, oxidative stress,
mitochondrial dysfunction and apoptosis in A549 cells.
AB - Fluoride (F) is an environmental contaminant and industrial pollutant. Molecular
mechanisms remain unclear in F induced pulmonary toxicity even after numerous
studies. Tamarind fruits act as defluoridating agents, but no study was conducted
in in vitro systems. Hence, we aimed to assess the ameliorative impact of the
tamarind seed coat extract (TSCE) against F toxicity utilizing lung epithelial
cells, A549. Cells were exposed to sodium fluoride (NaF-5 mM) alone and in
combination with TSCE (750 ng/ml) or Vitamin C (positive control) for 24 h and
analyzed for F content, intracellular calcium ([Ca(2+)]i) level, oxidative
stress, mitochondrial integrity and apoptotic markers. TSCE treatment prevented
the F induced alterations in [Ca(2+)]i overload, F content, oxidant (reactive
oxygen species generation, lipid peroxidation, protein carbonyl content and
nitric oxide) and antioxidant (superoxide dismutase, catalase, glutathione
peroxidase and glutathione) parameters. Further, TSCE modulates F activated
changes in mitochondrial membrane potential, permeability transition pore
opening, cytochrome-C release, Bax/Bcl-2 ratio, caspase-3 and PARP-1 expressions.
In conclusion, our study demonstrated that TSCE as a potential protective agent
against F toxicity, which can be utilized as a neutraceutical.
PMID- 26439940
TI - Highly efficient single cell arraying by integrating acoustophoretic cell pre
concentration and dielectrophoretic cell trapping.
AB - To array rare cells at the single-cell level, the volumetric throughput may
become a bottleneck in the cell trapping and the subsequent single-cell analysis,
since the target cells per definition commonly exist in a large sample volume
after purification from the original sample. Here, we present a novel approach
for high throughput single cell arraying by integrating two original microfluidic
devices: an acoustofluidic chip and an electroactive microwell array. The
velocity of the cells is geared down in the acoustofluidic chip while maintaining
a high volume flow rate at the inlet of the microsystem, and the cells are
subsequently trapped one by one into the microwell array using dielectrophoresis.
The integrated system exhibited a 10 times improved sample throughput compared to
trapping with the electroactive microwell array chip alone, while maintaining a
highly efficient cell recovery above 90%. The results indicate that the serial
integration of the acoustophoretic pre-concentration with the dielectrophoretic
cell trapping drastically improves the performance of the electroactive microwell
array for highly efficient single cell analysis. This simple and effective system
for high throughput single cell arraying with further possible integration of
additional functions, including cell sorting and downstream analysis after cell
trapping, has potential for development to a highly integrated and automated
platform for single-cell analysis of rare cells.
PMID- 26439941
TI - Lower Hydrogen Sulfide Is Associated with Cardiovascular Mortality, Which
Involves cPKCbetaII/Akt Pathway in Chronic Hemodialysis Patients.
AB - BACKGROUND/AIMS: To evaluate the relationship between plasma hydrogen sulfide
(H2S) and cardiovascular risk markers, including pulse pressure (PP), left
ventricular mass index (LVMI) and intima-media thickness (IMT), and mortality in
chronic hemodialysis (CHD) patients and further investigate the underlying
cardiovascular protection mechanism of H2S. METHODS: CHD patients, 113 of them,
were studied. Plasma H2S was measured through zinc acetate reaction. cPKCbetaII
membrane translocation and phosphorylation of Akt were detected by western blot.
RESULTS: Lower plasma H2S level in CHD patients was predictor of an increased PP,
LVMI and IMT. Patients with lower H2S had a lower survival at the end of the
study. H2S was an independent predictor of all-cause and cardiovascular mortality
when adjusted for other risk factors. CHD patients with lower H2S showed an
increase of cPKCbetaII activation, but phosphorylation of Akt decreased. The
level of VCAM-1 and ICAM-1 increased significantly. CONCLUSIONS: Lower plasma H2S
in CHD patients is associated with cardiovascular risk factors and mortality,
which may be mediated by the cPKCbetaII/Akt pathway and further VCAM-1/ICAM-1
upregulation.
PMID- 26439942
TI - Longitudinal Assessment of Blood Pressure in School-Aged Children: A 3-Year
Follow-Up Study.
AB - The purpose of this study was to assess the prevalence of abnormal blood pressure
in a population of school children during a 3-year follow-up period and its
relationship with obesity. Anthropometric and blood pressure data were collected
from a population of Italian school children during three consecutive years.
During each year blood pressure measurements were repeated three times, at
intervals of 1 week. A total of 564 school-children [311 boys; mean (SD) age 8.8
+/- 1.4 years] were recruited. During each year, systolic and diastolic blood
pressure decreased from visit 1 to visit 3 (p < 0.001). This was associated with
a decline in the percentage of prehypertension/hypertension from visit 1 to visit
3. An abnormal blood pressure value in at least one study visit was found in 8.8
17 % of children, whereas the prevalence of hypertension at all three study
visits was between 5.2 and 7.8 %, and that of prehypertension at all three visits
was between 2.8 and 3.8 %. High blood pressure was more frequent in obese
children. In this population of school children the percentage of
prehypertension/hypertension remarkably varied when based on one versus three
annual assessments, thus emphasizing the importance of repeated measurement
before making a diagnosis of abnormal blood pressure. Adiposity was confirmed to
be a determinant of high blood pressure.
PMID- 26439943
TI - Exercise Performance in Patients with D-Loop Transposition of the Great Arteries
After Arterial Switch Operation: Long-Term Outcomes and Longitudinal Assessment.
AB - The first patients to undergo a successful arterial switch operation (ASO) for d
transposition of the great arteries (D-TGA) are now entering their fourth decade
of life. Past studies of ASO survivors' exercise function have yielded
conflicting results. We therefore undertook this study to describe the current
function of ASO survivors, to identify factors related to inferior exercise
performance and to determine whether their exercise function tends to deteriorate
over time. A retrospective cohort study was designed examining all patients with
D-TGA after the ASO who underwent comprehensive cardiopulmonary exercise testing
(CPET). Patients with palliative surgery prior to ASO, ventricular hypoplasia or
severe valvar dysfunction were excluded from the study. Data from CPETs in which
the peak respiratory exchange ratio was <1.09 were also excluded. We identified
113 patients who met entry criteria and had 186 CPX at our institution between
1/2002 and 1/2013; 41 patients had at least 2 qualifying CPX. Mean age at the
time of the initial test was 17 +/- 1 year. Peak oxygen consumption (VO2)
averaged 84 +/- 2 % predicted. Peak VO2 was lower among patients with repaired
ventricular septal defects (82 +/- 4 vs. 86 +/- 3 % predicted; p < 0.05) and
among patients with >= moderate right-sided obstructive lesions (77 +/- 5 vs. 87
+/- 3 % predicted; p < 0.05). Surgery prior to 1991 was also associated with a
lower peak VO2 (81 +/- 3 vs. 87 +/- 3 % predicted; p < 0.01). The mean %
predicted peak heart rate was 92 +/- 1 %, with no significant difference between
any of the subgroups. Non-diagnostic exercise-induced STT changes developed in 10
patients (12 studies). In the subgroup with at least 2 exercise tests, the annual
decline in % predicted peak VO2 was quite slow (-0.3 % points/year; p < 0.01 vs.
expected normal age-related decline). The exercise capacity of ASO survivors is
well preserved and is only mildly reduced compared to normal subjects. Moreover,
there is only a slight deterioration in exercise capacity over time. VSD repair,
residual right-sided obstructive lesions, and earlier surgical era are associated
with worse exercise performance. Peak heart rate was preserved with no
significant change in follow up testing.
PMID- 26439944
TI - What is a clinically important change in the Unified Dyskinesia Rating Scale in
Parkinson's disease?
AB - INTRODUCTION: Dyskinesia remain a significant problem in Parkinson Disease (PD).
The translation process of novel drug targets for dyskinesia has proven difficult
with several failures at phase III level. Determining the 'clinically important
change' (CIC) for dyskinesia rating scales in phase II clinical trials may assist
in optimizing drug development of new anti-dyskinetic treatments. We used a
standard phase IIa acute levodopa infusion paradigm to determine for the first
time the CIC for dyskinesia using the new UDysRS. METHODS: We performed a
randomized, double-blind, placebo-controlled crossover study with eleven PD
patients with stable bothersome dyskinesia. We used the following patient
reported clinically important events as CIC anchors: onset, maximum intensity,
remission of dyskinesia. Objective dyskinesia scores using the UDysRS part III
Impairment were determined at these same events by blinded video-rating. The CIC
was determined using the 'within-patient' score change and a sensitivity- and
specificity-based approach. RESULTS: Patients were most aware of 'onset of
dyskinesia', followed by 'remission of dyskinesia'. An 11.1-point median change
(UDysRS Part III Impairment, p < 0.0001) was the CIC for patient-reported
remission of dyskinesia from a practically defined-OFF state. A 2.32-point change
(UDysRS Part III Impairment) had the best specificity and sensitivity to
distinguish between patient-reported remission and perception of dyskinesia.
CONCLUSIONS: In this study, we provide the first report of a CIC for the UDysRS
Part III Impairment. Early knowledge of a CIC may help inform the decision to
advance into phase III trials and contribute for a higher yield of success in
finding new anti-dyskinetic treatments.
PMID- 26439945
TI - Exercise-induced neuroplasticity in human Parkinson's disease: What is the
evidence telling us?
AB - INTRODUCTION: While animal models of exercise and PD have pushed the field
forward, few studies have addressed exercise-induced neuroplasticity in human PD.
METHOD: As a first step toward promoting greater international collaboration on
exercise-induced neuroplasticity in human PD, we present data on 8 human PD
studies (published between 2008 and 2015) with 144 adults with PD of varying
disease severity (Hoehn and Yahr stage 1 to stage 3), using various experimental
(e.g., randomized controlled trial) and quasi-experimental designs on the effects
of cognitive and physical activity on brain structure or function in PD. We focus
on plasticity mechanisms of intervention-induced increases in maximal
corticomotor excitability, exercise-induced changes in voxel-based gray matter
volume changes and increases in exercise-induced serum levels of brain derived
neurotrophic factor (BDNF). Finally, we provide a future perspective for
promoting international, collaborative research on exercise-induced
neuroplasticity in human PD. CONCLUSION: An emerging body of evidence suggests
exercise triggers several plasticity related events in the human PD brain
including corticomotor excitation, increases and decreases in gray matter volume
and changes in BDNF levels.
PMID- 26439947
TI - Optimizing diagnosis in Parkinson's disease: Radionuclide imaging.
AB - Parkinson's disease (PD) and other disorders characterized by basal ganglia
dysfunction are often associated with limited structural imaging changes that
might assist in the clinical or research setting. Radionuclide imaging has been
used to assess characteristic functional changes. Presynaptic dopaminergic
dysfunction in PD can be revealed through the imaging of different steps in the
process of dopamine synthesis and storage: L-aromatic amino acid decarboxylase
(AADC) activity, Vesicular Monoamine Transporter type 2 (VMAT2) binding or its
reuptake via the dopamine transporter (DAT). Postsynaptic dopamine dysfunction
can also be studied with a variety of different tracers that primarily assess D2
like dopamine receptor availability. The function of other neurotransmitters such
as norepinephrine, serotonin and acetylcholine can be imaged as well, giving
important information about the underlying pathophysiologic process of PD and its
complications. The imaging of metabolic activity and pathologic changes has also
provided great advances in the field. Together, these techniques have allowed for
a better understanding of PD, may be of aid for differentiating PD from other
forms of parkinsonism and will undoubtedly be useful for the establishment of new
therapeutic targets.
PMID- 26439946
TI - Biomarkers in Parkinson's disease: Advances and strategies.
AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
progressive motor disturbances and affects more than 1% of the worldwide
population. Despite considerable progress in understanding PD pathophysiology,
including genetic and biochemical causes, diagnostic approaches lack accuracy and
interventions are restricted to symptomatic treatments. PD is a complex syndrome
with different clinical subtypes and a wide variability in disorder course. In
order to deliver better clinical management of PD patients and discovery of novel
therapies, there is an urgent need to find sensitive, specific, and reliable
biomarkers. The development of biomarkers will not only help the scientific
community to identify populations at risk, but also facilitate clinical
diagnosis. Furthermore, these tools could monitor progression, which could
ultimately deliver personalized therapeutic strategies. The field of biomarker
discovery in PD has attracted significant attention and there have been numerous
contributions in recent years. Although none of the parameters have been
validated for clinical practice, some candidates hold promise. This review
summarizes recent advances in the development of PD biomarkers and discusses new
strategies for their utilization.
PMID- 26439948
TI - Stiffness of Hydrogels Regulates Cellular Reprogramming Efficiency Through
Mesenchymal-to-Epithelial Transition and Stemness Markers.
AB - The stiffness of hydrogels has been reported to direct cell fate. Here, we found
that the stiffness of hydrogels promotes the reprogramming of mouse embryonic
fibroblasts into induced pluripotent stem cells (iPSCs). We prepared cell culture
substrates of various stiffnesses (0.1, 1, 4, 10, and 20 kPa) using a
polyacrylamide hydrogel. We found that culture on a soft hydrogel plays an
important role in inducing cellular reprogramming into iPSCs via activation of
mesenchymal-to-epithelial transition and enhancement of stemness marker
expression. These results suggest that physical signals at the interface between
cell and substrate can be used as a potent regulator to promote cell fate changes
associated with reprogramming into iPSCs, which may lead to effective and
reproducible iPSC-production.
PMID- 26439950
TI - The functional organization of motor nerve terminals.
AB - Neuromuscular junctions (NMJs) have long been studied as particularly accessible
examples of chemical synapses. Nonetheless, some important features of
neuromuscular transmission are still poorly understood. One of these is the low
statistical variability of the number of transmitter quanta released from motor
nerve terminals by successive nerve impulses. This variability is well-described
by a binomial distribution, suggesting that the quanta released are drawn, at
high probability, from a small subset of those in the terminals. However, the
nature of that subset remains unclear. In an effort to clarify what is
understood, and what is not, about quantal release at NMJs, this review addresses
the relationship between NMJ structure and function. After setting the biological
context in which NMJs operate, key aspects of the variability of release and the
structure of the motor nerve terminals are described. These descriptions are then
used to explore the functional logic of motor nerve terminal organization and the
structural basis of the low variability of release. This analysis supports the
suggestion that the probability of release differs significantly at the different
'active zones' from which quanta are released. Finally, after a brief
consideration of how release is maintained in the long term, a comparison is made
of the features of NMJs with those of some well-studied neuronal synapses. An
important conclusion is that NMJs share some important features with neuronal
synapses, so continuing efforts to understand how motor nerve terminals work are
likely to have much more general implications.
PMID- 26439949
TI - Tumor-induced solid stress activates beta-catenin signaling to drive malignant
behavior in normal, tumor-adjacent cells.
AB - Recent work by Fernandez-Sanchez and coworkers examining the impact of applied
pressure on the malignant phenotype of murine colon tissue in vivo revealed that
mechanical perturbations can drive malignant behavior in genetically normal
cells. Their findings build upon an existing understanding of how the mechanical
cues experienced by cells within a tissue become progressively modified as the
tissue transforms. Using magnetically stimulated ultra-magnetic liposomes to
mimic tumor growth -induced solid stress, Fernandez-Sanchez and coworkers were
able to stimulate beta-catenin to promote the cancerous behavior of both a normal
and genetically modified colon epithelium. In this perspective, we discuss their
findings in the context of what is currently known regarding the role of the
mechanical landscape in cancer progression and beta-catenin as a
mechanotransducer. We review data that suggest that mechanically regulated
activation of beta-catenin fosters development of a malignant phenotype in tissue
and predict that mechanical cues may contribute to tumor heterogeneity.
PMID- 26439951
TI - Serum insulin-like growth factor-I and amyloid beta protein in Alzheimer's
disease: relationship with cognitive function.
AB - AIMS: Previous studies have suggested that insulin-like growth factor-I (IGF-I)
deficiency may lead to cognitive deficits in neurodegenerative diseases such as
Alzheimer's disease. The present study aimed to investigate the possible
relationship between cognitive function and concentration of IGF-I or amyloid
beta protein (Abeta) in serum in Alzheimer's patients. METHODS: A total of 81
Japanese patients were enrolled in this study. Concentrations of IGF-I, Abeta42,
and Abeta40 in serum were measured. Two neuropsychological tests, Mini-Mental
State Examination and Hasegawa's Dementia Scale-Revised (HDS-R), were also
performed. Linear correlations among the age, serum IGF-I, serum Abeta42 or
Abeta40, Abeta42/Abeta40 ratio, Mini-Mental State Examination or HDS-R total
score, and the scores for six HDS-R subscales were analyzed by regression
analysis. RESULTS: IGF-I showed a significant negative correlation with age (beta
= -0.357, P = 0.002) and a positive correlation with Abeta42/Abeta40 ratio (beta
= 0.318, P = 0.007). Serum IGF-I and both the Mini-Mental State Examination and
the HDS-R total score also correlated (beta = 0.505, beta = 0.524, P < 0.01).
Among the HDS-R subscales, 'Recall' (rho = 0.379, P < 0.01), 'Verbal fluency'
(rho = 0.360, P < 0.01), and 'Attention and calculation' (rho = 0.389, P < 0.01)
showed significant positive correlations with serum IGF-I. CONCLUSION: The
results, specifically that lower serum IGF-I was associated with cognitive
impairment, suggest that metabolism of IGF-I may be involved in the pathogenesis
of cognitive deficits in Alzheimer's disease.
PMID- 26439952
TI - Trajectories of subcortical volume change in schizophrenia: A 5-year follow-up.
PMID- 26439953
TI - Catalytic autoantibodies against myelin basic protein (MBP) isolated from serum
of autistic children impair in vitro models of synaptic plasticity in rat
hippocampus.
AB - Autoantibodies from autistic spectrum disorder (ASD) patients react with multiple
proteins expressed in the brain. One such autoantibody targets myelin basic
protein (MBP). ASD patients have autoantibodies to MBP of both the IgG and IgA
classes in high titers, but no autoantibodies of the IgM class. IgA
autoantibodies act as serine proteinases and degrade MBP in vitro. They also
induce a decrease in long-term potentiation in the hippocampi of rats either
perfused with or previously inoculated with this IgA. Because this class of
autoantibody causes myelin sheath destruction in multiple sclerosis (MS), we
hypothesized a similar pathological role for them in ASD.
PMID- 26439954
TI - Autoantibodies against vinculin in patients with chronic inflammatory
demyelinating polyneuropathy.
AB - To identify the target molecules of chronic inflammatory demyelinating
polyneuropathy (CIDP), we used proteomic-based approach in the extracted proteins
from porcine cauda equina. Two of 31 CIDP patients had markedly elevated serum
autoantibodies against vinculin, a cell adhesion protein. Both of the patients
with anti-vinculin antibodies had similar clinical manifestation, which are
compatible with those of "typical" CIDP. Immunocytochemistry showed that vinculin
was stained at the myelin sheath of the sciatic nerves by serum samples. Our
results suggest that vinculin is a possible immunological target molecule in a
subpopulation of typical CIDP patients.
PMID- 26439955
TI - Increased serum peroxiredoxin 5 levels in myasthenia gravis.
AB - Extracellular peroxiredoxin 5 (PRX5) is known to be an inflammatory mediator. The
serum PRX5 levels of 40 patients with anti-acetylcholine receptor antibody
positive MG and those of 40 controls were measured. PRX5 levels in patients with
MG were higher than those in the controls (P=0.045). Thymoma-associated MG
patients showed higher PRX5 levels than late-onset MG patients and controls
(P<0.05). There were significant associations between the serum PRX5 levels and
high mobility group box 1 levels. PRX5 elevation in MG could be related to the
neuromuscular junction breakdown and plays a pivotal role in the pathogenic
inflammation of MG.
PMID- 26439956
TI - Heat shock protein 70 (Hsp70) interacts with the Notch1 intracellular domain and
contributes to the activity of Notch signaling in myelin-reactive CD4 T cells.
AB - Notch receptors (Notch1-4) are involved in the differentiation of CD4 T cells and
the development of autoimmunity. Mechanisms regulating Notch signaling in CD4 T
cells are not fully elucidated. In this study we investigated potential crosstalk
between Notch pathway molecules and heat shock protein 70 (Hsp70), the major
intracellular chaperone involved in the protein transport during immune responses
and other stress conditions. Using Hsp70(-/-) mice we found that Hsp70 is
critical for up-regulation of NICD1 and induction of Notch target genes in
Jagged1- and Delta-like1-stimulated CD4 T cells. Co-immunoprecipitation analysis
of wild-type CD4 T cells stimulated with either Jagged1 or Delta-like1 showed a
direct interaction between NICD1 and Hsp70. Both molecules co-localized within
the nucleus of CD4 T cells stimulated with Notch ligands. Molecular interaction
and nuclear colocalization of NICD1 and Hsp70 were also detected in CD4 T cells
reactive against myelin oligodendrocyte glycoprotein (MOG)35-55, which showed
Hsp70-dependent up-regulation of both NICD1 and Notch target genes. In
conclusion, we demonstrate for the first time that Hsp70 interacts with NICD1 and
contributes to the activity of Notch signaling in CD4 T cells. Interaction
between Hsp70 and NICD1 may represent a novel mechanism regulating Notch
signaling in activated CD4 T cells.
PMID- 26439957
TI - Hypertrophic pachymeningitis accompanying neuromyelitis optica spectrum disorder:
A case report.
AB - We report a case of idiopathic cerebral hypertrophic pachymeningitis accompanying
neuromyelitis optica spectrum disorder. No other identifiable cause of
pachymeningitis was detected. Corticosteroid therapy was effective for both
diseases. Hypertrophic pachymeningitis is closely related to autoimmune
inflammatory disease of the central nervous system. This case supports the
hypothesis that hypertrophic pachymeningitis can be a rare comorbidity of
neuromyelitis optica spectrum disorder.
PMID- 26439958
TI - Favorable outcome of granulocyte colony-stimulating factor use in neuromyelitis
optica patients presenting with agranulocytosis in the setting of rituximab.
AB - Neuromyelitis optica is a severe autoimmune condition affecting the central
nervous system characterized by a relapsing disease course. Rituximab is a
chimeric monoclonal antibody against the protein CD20, and is one of the most
utilized medications for management of this disease. A known complication of
rituximab use is neutropenia. We report on two patients who developed symptomatic
early-onset rituximab-induced agranulocytosis who safely received granulocyte
colony-stimulating factor. Neutrophil counts recovered quickly and both patients
continue to receive rituximab without further incident.
PMID- 26439959
TI - Clinico-pathological correlation in adenylate kinase 5 autoimmune limbic
encephalitis.
AB - Autoantibodies associated with autoimmune limbic encephalitis (ALE) have been
well-characterized, with intracellular neuronal antibodies being less responsive
to immunotherapy than antibodies to cell surface antigens. Adenylate kinase 5
(AK5) is a nucleoside monophosphate kinase vital for neuronal-specific metabolism
and is located intracellularly in the cytosol and expressed exclusively in the
brain. Antibodies to AK5 had been previously identified but were not known to be
associated with human disease prior to the report of two patients with AK5
related ALE (Tuzun et al., 2007). We present the complete clinical picture for
one of these patients and the first reported neuropathology for AK5 ALE.
PMID- 26439961
TI - Experimental autoimmune encephalomyelitis and age-related correlations of NADPH
oxidase, MMP-9, and cell adhesion molecules: The increased disease severity and
blood-brain barrier permeability in middle-aged mice.
AB - The aim of the present study was to investigate effect of two different ages (6
weeks [6 W] vs. 6 months [6 M]) on blood-brain barrier (BBB) disruption in EAE
and evaluate the expression and correlations of NADPH oxidase, MMP-9, ICAM-1, and
VCAM-1 following increased age and EAE induction. Higher disease severity was
observed in 6 M-EAE than 6 W-EAE. The four factors were significantly elevated
and correlated in 6 M-EAE. BBB permeability increased with statistically
significant interaction between age and EAE effects. We suggest strong
correlations between NADPH oxidase and the other factors play important roles in
increased BBB disruption and EAE susceptibility in middle-aged mice.
PMID- 26439962
TI - Alzheimer's disease vaccine development: A new strategy focusing on immune
modulation.
AB - Despite significant advances in the development of Alzheimer's disease (AD)
vaccines effective in animal models, these prototypes have been clinically
unsuccessful; apparently the result of using immunogens modified to prevent
inflammation. Hence, a new paradigm is needed that uses entire AD-associated
immunogens, a notion supported by recent successful passive immunotherapy
results, with adjuvants that induce Th2-only while inhibiting without abrogating
Th1 immunity. Here, we discuss the obstacles to AD vaccine development and Th2
adjuvants that by acting on dendritic and T cells, would elicit regardless of the
antigen a safe and effective antibody response, while preventing damaging
neuroinflammation and ameliorating immunosenescence.
PMID- 26439960
TI - Gelsolin decreases actin toxicity and inflammation in murine multiple sclerosis.
AB - Gelsolin is the fourth most abundant protein in the body and its depletion in the
blood has been found in multiple sclerosis (MS) patients. How gelsolin affects
the MS brain has not been studied. We found that while the secreted form of
gelsolin (pGSN) decreased in the blood of experimental autoimmune
encephalomyelitis (EAE) mice, pGSN concentration increased in the EAE brain.
Recombinant human pGSN (rhp-GSN) decreased extracellular actin and
myeloperoxidase activity in the brain, resulting in reduced disease activity and
less severe clinical disease, suggesting that gelsolin could be a potential
therapeutic target for MS.
PMID- 26439963
TI - Higher expression of IL-12Rbeta2 is associated with lower risk of relapse in
relapsing-remitting multiple sclerosis patients on interferon-beta1b therapy
during 3-year follow-up.
AB - Cytokines produced by helper T (Th)1 cells, Th17 and regulatory T cells (Treg)
are involved in multiple sclerosis (MS) immunopathogenesis. Interferon (IFN)-beta
alters the numerous genes' expression, but how this alteration affects the
treatment response is still elusive. We assessed relative gene expression of
nineteen Th1/Th17/Treg-associated mediators in peripheral blood mononuclear cells
and plasma levels of GM-CSF, IL-17A and IL-17F, in relapsing-remitting MS (RRMS)
patients before IFN-beta1b treatment initiation and at 6, 12, 24 and 36 months of
therapy. All mRNA levels changed significantly during the IFN-beta1b therapy.
Higher IL-12Rbeta2 mRNA levels were associated with lower risk of relapse.
Despite recent reports regarding role of GM-CSF in MS, our study failed to
demonstrate its significance as therapy response biomarker, both on the mRNA and
protein level.
PMID- 26439964
TI - Recombinant adenovirus encoding NLRP3 RNAi attenuate inflammation and brain
injury after intracerebral hemorrhage.
AB - Numerous evidence have shown that microglia mediated inflammation plays a pivotal
role in the development of brain injury after intracerebral hemorrhage (ICH).
Therefore anti-inflammation therapy represents a potentially promising approach
to ICH. Recently, NLRP3 inflammasome was discovered to facilitate the
inflammatory response. However, the effect of NLRP3 inflammasome after ICH has
not been fully studied. To explore the potential of NLRP3 inflammasome, we
detected NLRP3 expression, inflammation, brain edema and neurological functions
in vitro and in vivo. We found that ICH activated the NLRP3 inflammasome and
inflammation. However, NLRP3 RNAi could attenuate inflammation and brain injury
after ICH. Therefore, the findings suggested that recombinant adenovirus encoding
NLRP3 RNAi might be valuable as a potential strategy for anti-inflammation
therapy in ICH.
PMID- 26439965
TI - Upregulation of integrin expression on monocytes in multiple sclerosis patients
treated with natalizumab.
AB - Natalizumab is a humanized monoclonal antibody against the alpha4 subunit of VLA
4 integrin that is used to treat conditions such as multiple sclerosis (MS).
Although its effects on lymphocytes have been widely described, little is known
about its effects on monocytes. Here we described the effects of natalizumab
treatment on peripheral blood monocytes from a small cohort of MS patients in
terms of relative frequencies and surface integrin (CD49d and CD18) expression.
We showed that natalizumab treatment altered the surface integrin expression on
monocyte subsets in the peripheral compartment, suggesting a role for them as
mediators of natalizumab effects.
PMID- 26439966
TI - Role of inflammation and apoptosis in multiple sclerosis: Comparative analysis
between the periphery and the central nervous system.
AB - Multiple sclerosis (MS) is a complex, multifactorial disease associated with
damage to the axonal myelin sheaths and neuronal degeneration. The pathognomonic
event in MS is oligodendrocyte loss accompanied by axonal damage, blood-brain
barrier leakage, inflammation and infiltration of immune cells. The
etiopathogenesis of MS is far from being elucidated. However, increasing evidence
suggests that the inflammatory and apoptotic responses, occurring in patients
either at the peripheral level or the central nervous system (CNS), can play a
role. In this review, we give a comprehensive picture of general aspects of
inflammation and apoptosis in MS, with special emphasis on the until now not well
highlighted possible links between phenomena relevant to these aspects occurring
in either the periphery or in the CNS during MS.
PMID- 26439967
TI - Neurocognitive function, brain-derived neurotrophic factor (BDNF) and IL-6 levels
in cancer patients with depression.
AB - BACKGROUND: Increased IL-6 and decreased brain-derived neurotrophic factor (BDNF)
levels have been implicated in the pathophysiology of depression. The objective
was to assess the influence of BDNF and IL-6 on cognitive function and depression
in patients with cancer. METHODS: Serum BDNF and plasma IL-6 were measured in
patients with metastatic cancer. Diagnosis of depression was established
according to DSM-IV criteria. Cognitive function was assessed by the Verbal
Learning and Memory Test (VLMT). RESULTS: A total of 59 patients were recruited
in this study. Only IL-6 levels were significantly elevated in patients with
clinical depression (35.7 vs. 6.9 pg/ml; p<0.001). There were no differences in
hemoglobin levels (p=0.3) or BDNF levels (p=0.16). Patients with clinical
depression showed significant impairment of short-term memory (STM) (24.4 vs.
37.5; p=0.01), but not of long-term memory (LTM) (3.9 vs. 2.8; p=0.3). STM was
dependent on the level of BDNF and younger age (b=0.60; p=0.001; b= -0.63;
p=0.003, respectively). IL-6 was not only strongly associated with depression,
but was an independent predictor of BDNF level as well (b= -0.50; p=0.01). LTM
was associated only with a good KPS (b=0.47; p=0.037). Hemoglobin levels and the
prior number of chemotherapy lines were not predictive of memory performance.
CONCLUSIONS: Low BDNF is associated with cognitive impairment, STM, in patients
with cancer, however no influence on depression could be found. IL-6 is strongly
associated with depression and an independent predictor of BDNF levels.
PMID- 26439968
TI - The spectrum of autoimmune encephalopathies.
AB - Despite being a potentially reversible neurological condition, no clear
guidelines for diagnosis or management of autoimmune encephalitis exist. In this
study we analyzed clinical presentation, laboratory and imaging characteristics,
and outcome of autoimmune encephalitis from three teaching hospitals. Non
paraneoplastic autoimmune encephalitis associated with antibodies against
membrane antigens was the most common syndrome, especially in the pediatric
population. Clinical outcome was better for patients with shorter latency from
symptom onset to diagnosis and initiation of immunomodulation. Patients with
underlying malignancy were less likely to respond well to immunomodulatory
therapy. The clinical spectrum of autoimmune encephalitis is fairly broad, but
prompt recognition and treatment often leads to excellent outcome.
PMID- 26439969
TI - Impact of glatiramer acetate on paraclinical markers of neuroprotection in
multiple sclerosis: A prospective observational clinical trial.
AB - Data from in vitro and animal studies support a neuroprotective role of
glatiramer acetate (GA) in multiple sclerosis (MS). We investigated prospectively
whether treatment with GA leads to clinical and paraclinical changes associated
with neuroprotection in patients with relapsing-remitting (RR) MS. Primary aim of
this clinical study was to determine serum BDNF levels in RR-MS patients who were
started on GA as compared to patients who remained therapy-naive throughout 24
months. Secondary outcomes included relapses and EDSS, cognition, quality of
life, fatigue and depression, BDNF expression levels on peripheral immune cells
(FACS, RT-PCR), serum anti-myelin basic peptide (MBP) antibody status, evoked
potential and cerebral MRI studies. While GA treatment did not alter serum levels
or expression levels on peripheral immune cells of BDNF over time it resulted in
a transient increase of serum IgG antibody response to MBP, mainly due to subtype
IgG1 (p<0.05), after 3 months. However, no significant differences were found
between GA treated and therapy-naive patients with regard to serum BDNF and
intracellular BDNF expression levels, nerve conduction (including median and
tibial nerve somatosensory, pattern-shift visual and upper and lower limb motor
evoked potentials) or MRI (including volume of hyperintense lesions, volume of
hypointense lesions after CE, mean diffusivity and fractional anisotropy) outcome
parameters. In conclusion, our findings do not support a major impact of GA
treatment on paraclinical markers of neuroprotection in human RR-MS.
PMID- 26439970
TI - Early culture conversion and cure for extensively drug-resistant tuberculosis is
possible with appropriate treatment: lessons learnt from a case study in South
Africa.
AB - Despite the relevance of extensively drug-resistant tuberculosis (XDR-TB) to
global TB control efforts, case reports on patients achieving cure are scarce.
The case of a patient who was treated for more than 3 years as a multidrug
resistant TB (MDR-TB) case, and who was diagnosed retrospectively with XDR-TB, is
presented herein. Soon after the initiation of a capreomycin and para
aminosalicylic acid-based regimen, the patient converted and treatment was
completed successfully.
PMID- 26439971
TI - Dynamics of immune parameters during the treatment of active tuberculosis showing
negative interferon gamma response at the time of diagnosis.
AB - OBJECTIVES: In the performance of interferon gamma release assays (IGRA) for the
diagnosis of tuberculosis (TB) infection, false-negative results are a major
obstacle. In active TB patients, treatment-dependent changes of the negative test
results remain unknown. METHODS: The treatment course of 19 smear
positive/culture-confirmed TB patients who had IGRA-negative results by
QuantiFERON-TB in-tube (QFT-IT) method at the time of diagnosis (month 0) in a
previous study, were monitored in the present study. Blood was further collected
at months 2 and 7, and the concentrations of 27 immune molecules were measured in
the plasma supernatants remaining after performing the IGRA, using a suspension
array system. RESULTS: After initiating treatment, eight of the 19 QFT-IT
negative patients showed positive conversion, whereas the remaining 11 (58%) did
not; the interferon gamma (IFN-gamma) response was restored to levels higher than
1 IU/ml in only three of the eight patients with positive conversion. Plasma
concentrations of interleukin 1 receptor antagonist, interleukin 2, and
interferon gamma-induced protein 10 remained low after Mycobacterium tuberculosis
specific antigen stimulation at months 2 and 7 in the continuously QFT-IT
negative group, whereas the parameters were elevated only in the transiently QFT
IT-negative group. CONCLUSIONS: It was demonstrated that a majority of active TB
patients showing negative IGRA results did not regain sufficient levels of immune
responsiveness despite successful treatment.
PMID- 26439972
TI - The role of a scientific journal in psychiatric research.
PMID- 26439973
TI - Authors' response re: Valentini P, Nelson P. Letter to the Editor Re: Awada HK,
Fletter PC, Zaszczurynski PJ, Cooper MA, Damaser MS. Conversion of urodynamic
pressures measured simultaneously by air-charged and water-filled catheter
systems. Neurourol Urodyn. 2015;34:507-12.
PMID- 26439974
TI - Enantiodivergent Synthesis of Bis-Spiropyrrolidines via Sequential Interrupted
and Completed (3 + 2) Cycloadditions.
AB - Both (5R)- and (5S)-1,7-diazaspiro[4.4]nonan-6-ones are obtained via a sequence
of interrupted and completed stepwise (3 + 2) cycloadditions between azomethine
ylides and pi-deficient alkenes. The only source of chirality along the whole
process is an enantiopure ferrocenyl pyrrolidine catalytic ligand. When the
starting imine incorporates two aryl groups or one aryl group with one electron
releasing substituent, the reaction between the azomethine ylide and the alkene
stops at the first step, leading to the corresponding Michael adduct. When imines
derived from p-methoxybenzaldehyde are used, the corresponding syn-alpha-amino
gamma-nitro ester is obtained with almost complete enantiocontrol. In contrast,
imines derived from benzophenone lead to the corresponding anti analogue. From
this interrupted (3 + 2) cycloaddition, cis- and trans-alpha-amino-gamma-lactams
can be obtained via hydrogenation of the nitro group followed by in situ
cyclization. Imines derived from these latter compounds are the precursors of N
metalated azomethine ylides from which up to four new chiral centers can be
generated via completed (3 + 2) cycloaddition reactions with full regio- and
diastereocontrol. Cis- and trans-gamma-lactams lead to opposite bis
spiropyrrolidine enantiomers. Therefore, both enantiomeric series of spiro
compounds can be obtained by means of the same catalytic system. The potential of
these rigid, densely substituted homochiral compounds in medicinal chemistry is
briefly described.
PMID- 26439975
TI - Impact of nutritional labelling on 10-d energy intake, appetite perceptions and
attitudes towards food.
AB - The purpose of this study was to investigate the impact of nutritional labelling
on energy intake, appetite perceptions and attitudes towards food. During a 10-d
period, seventy normal-weight (BMI<25 kg/m2) and seventy-one obese women (BMI>=30
kg/m2) were given three meals per d under ad libitum conditions. Participants
were randomly assigned to one of three experimental labelling groups in which the
only difference was the label posted on lunch meal entree: (1) low-fat label, (2)
energy label (energy content of the entree and average daily needs) and (3) no
label (control). Average energy intake was calculated by weighing all foods
before v. after daily consumption. Hunger and fullness perceptions were rated on
visual analogue scales immediately before and after each meal. Satiety efficiency
was assessed through the calculation of the satiety quotient (SQ). The
appreciation and perceived healthiness of the lunch entrees were rated on eight
point Likert scales. There was no difference in energy intake, SQ and attitudes
towards food between the three labelling groups. Fasting hunger perception was
higher in the low-fat label group compared with the two others groups (P=0.0037).
No interactions between labelling groups and BMI categories were observed. In
conclusion, although labelling does not seem to influence energy intake, a low
fat label may increase women's fasting hunger perceptions compared with an energy
label or no label.
PMID- 26439976
TI - Lipid Profiles and Signals for Long Life.
AB - Historically, fat was considered detrimental to health and lifespan. However,
lipidomics, the quantification of all lipid molecules in a biological sample, and
genetic studies in model organisms are revealing specific fats that may promote
longevity. These emerging findings provide insight into the complex relationship
between lipids and longevity.
PMID- 26439978
TI - Analytical Lipidomics in Metabolic and Clinical Research.
AB - Lipidomic analysis, which enables comprehensive characterization of molecular
lipids in biological systems, is rapidly becoming an essential tool in biomedical
research. While lipidomics already have contributed to several conceptual
advances in metabolic research and led to new, validated disease biomarkers, its
translation into the clinic remains a challenge.
PMID- 26439977
TI - The Genetics of Pediatric Obesity.
AB - Obesity among children and adults has notably escalated over recent decades and
represents a global major health problem. We now know that both genetic and
environmental factors contribute to its complex etiology. Genome-wide association
studies (GWAS) have revealed compelling genetic signals influencing obesity risk
in adults. Recent reports for childhood obesity revealed that many adult loci
also play a role in the pediatric setting. Childhood GWAS have uncovered novel
loci below the detection range in adult studies, suggesting that obesity genes
may be more easily uncovered in the pediatric setting. Shedding light on the
genetic architecture of childhood obesity will facilitate the prevention and
treatment of pediatric cases, and will have fundamental implications for diseases
that present later in life.
PMID- 26439979
TI - Emerging Hubs in Plant Light and Temperature Signaling.
AB - Due to their nature as sessile organisms, plants must accurately sense their
surroundings and then translate this information into efficient acclimation
responses to maximize development. Light and temperature are two major stimuli
that provide immediate cues regarding energy availability, daylength, proximity
of other species and seasonal changes. Both cues are sensed by complex systems
and the integration of these signals is of very high value to properly respond to
environmental changes without being disguised by random changes. For instance a
cold day has a different significance if it occurs during the illuminated phase
of the day or during the night, or when days are shortening during the fall
instead of a long-day in spring. Here, we summarize recent advances in the nature
of signaling components that operate as connectors of light and temperature
signaling, with emphasis on the emerging hubs. Despite the nature of the
thermosensors is still in its infancy compared to an important body of knowledge
about plant sensory photoreceptors, the interaction of both types of signaling
will not only bring clues of how plants integrate environmental information, but
also will help in leading research in the nature of the thermosensors themselves.
PMID- 26439980
TI - Preparation, Structural Determination, and Characterization of Electronic
Properties of Bis-silylated and Bis-germylated Lu3 N@Ih -C80.
AB - Bis-silylated and bis-germylated derivatives of Lu3 N@Ih -C80 (3, 4, 5) were
successfully synthesized by the photochemical addition of disiliranes 1 a, 1 b or
digermirane 2, and fully characterized by spectroscopic, electrochemical, and
theoretical studies. Interestingly, digermirane 2 reacts more efficiently than
disiliranes 1 a and 1 b because of its good electron-donor properties and lower
steric hindrance around the Ge-Ge bond. The 1,4-adduct structures of 3, 4, 5 were
unequivocally established by single-crystal X-ray crystallographic analyses. The
electrochemical and theoretical studies reveal that the energy gaps between the
highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular
orbital (LUMO) of the 1,4-adducts are remarkably smaller than those of Lu3 N@Ih
C80 , because the electron-donating groups effectively raise the HOMO levels. It
is also observed that germyl groups are slightly more electron-donating than the
silyl groups on the basis of the redox properties and the HOMO-LUMO energies of 4
and 5. Bis-silylation and bis-germylation are effective and versatile methods for
tuning the electronic characteristics of endohedral metallofullerenes.
PMID- 26439981
TI - Submolecular Plasticization Induced by Photons in Azobenzene Materials.
AB - We demonstrate experimentally for the first time that the illumination of
azobenzene derivatives leads to changes in molecular environment similar to those
observed on heating but that are highly heterogeneous at the submolecular scale.
This localized photoplasticization, which can be associated with a free volume
gradient, helps to understand the puzzling phenomenon of photoinduced macroscopic
material flow and photoexpansion upon illumination far below the glass transition
temperature (T(g)). The findings stem from the correlation of infrared (IR)
spectral band shifts measured upon illumination with those measured at controlled
temperatures for two amorphous DR1-functionalized azo derivatives, a polymer,
pDR1A, and a molecular glass, gDR1. This new approach reveals that IR
spectroscopy can be used as an efficient label-free molecular-scale thermometer
that allows the assignment of an effective temperature (T(eff)) to each moiety in
these compounds when irradiated. While no band shift is observed upon
illumination for the vibrational modes assigned to backbone moieties of pDR1A and
gDR1 and a small band shift is found for the spacer moiety, dramatic band shifts
are recorded for the azo moiety, corresponding to an increase in T(eff) of up to
nearly 200 degrees C and a molecular environment that is equivalent to thermal
heating well above the bulk T(g) of the material. An irradiated azo-containing
material thus combines characteristic properties of amorphous materials both
below and above its bulk T(g). The direct measurement of T(eff) is a powerful
probe of the local environment at the submolecular scale, paving the way toward
better rationalization of photoexpansion and the athermal malleability of azo
containing materials upon illumination below their T(g).
PMID- 26439982
TI - Cortical evolution 2015: Discussion of neural progenitor cell nomenclature.
PMID- 26439983
TI - Childhood trauma and suicide risk in the population living in Zonguldak Province.
AB - INTRODUCTION: No previous study has investigated the association between early
trauma and suicidal behavior in Zonguldak. The aim of this study was to
investigate the incidence of childhood abuse and neglect in the general
population living in Zonguldak province and the relationship between childhood
trauma and suicidal ideations and attempts. METHODS: The present study was
carried out with 897 people in the general population, as assessed in a
representative sample from Zonguldak province. The cluster sampling method was
used. After obtaining written consent from the people who agreed to participate
in the study, the Socio-demographic Information Form, Suicide Probability Scale,
Childhood Trauma Questionnaire, Beck Depression Inventory, and Beck Anxiety
Inventory were administered. RESULTS: The lifetime prevalence of suicidal
ideations was 18.3% among those who experienced at least one type of early
trauma, and it was 9.6% among those without a history of childhood trauma (P <
0.001). Only emotional abuse exhibited a significantly high odds ratio for
lifetime suicidal ideations (odds ratio [OR] = 3.168, 95% confidence interval
[CI] = 1.731-5.798) and attempts (OR = 3.467, 95% CI = 1.343-8.952). Emotional
neglect showed a high odds ratio only for lifetime suicidal attempts (OR = 3.282,
95% CI = 1.287-8.371). There were significant correlations among the Beck
Depression Inventory, Beck Anxiety Inventory, and Suicidal Probability Scale sub
scores and all six Childhood Trauma Questionnaire scores. DISCUSSION: Emotional
abuse and neglect in childhood are significantly associated with lifetime
suicidal ideations and attempts in the general population living in Zonguldak
province. Therefore, clinicians should be aware of the importance of the
childhood trauma in the patients with suicidal ideations and attempts.
PMID- 26439984
TI - Accelerating SNARE-Mediated Membrane Fusion by DNA-Lipid Tethers.
AB - SNARE proteins are the core machinery to drive fusion of a vesicle with its
target membrane. Inspired by the tethering proteins that bridge the membranes and
thus prepare SNAREs for docking and fusion, we developed a lipid-conjugated ssDNA
mimic that is capable of regulating SNARE function, in situ. The DNA-lipid
tethers consist of a 21 base pairs binding segment at the membrane distal end
that can bridge two liposomes via specific base-pair hybridization. A linker at
the membrane proximal end is used to control the separation distance between the
liposomes. In the presence of these artificial tethers, SNARE-mediated lipid
mixing is significantly accelerated, and the maximum fusion rate is obtained with
the linker shorter than 40 nucleotides. As a programmable tool orthogonal to any
native proteins, the DNA-lipid tethers can be further applied to regulate other
biological processes where capturing and bridging of two membranes are the
prerequisites for the subsequent protein function.
PMID- 26439986
TI - Estradiol induces apoptosis via activation of miRNA-23a and p53: implication for
gender difference in liver cancer development.
AB - Estrogen (E2) has been suggested to have a protective role in attenuating
hepatocellular carcinoma (HCC) development. miRNAs have great potential as
biomarkers and therapeutic agents owing to their ability to control gene
expression. However, little is known about the mechanism underlying the
protective role of E2 in hepatocarcinogenesis and the effects of E2 on apoptotic
miRNAs expression. Using miRNA PCR array, we found more than 2-fold alteration
was observed in 25 upregulated and 10 downregulated apoptotic miRNAs in E2
treated cells. Among these miRNAs, we found expression of miR-23a was related to
p53 functional status in the male-derived liver cell-lines. We demonstrated that
E2 via ERalpha transcriptionally activated miR-23a and p53 expression, and thus
enhanced p53 activation of miR-23a expression. Moreover, miR-23a expression
correlated inversely with the expression of target gene X-linked inhibitor of
apoptosis protein (XIAP), but positively with the caspase-3/7 activity.
Decreasing of XIAP might contribute to caspase-3 activity and cell apoptosis.
Taken together, our findings reveal a novel E2-signaling mechanism in regulating
miRNAs expression for controlling apoptosis in liver cells. Delineating the role
of E2 in regulating the activation of p53 and miR-23a, expression in HCC is
crucial to the understanding of the sex difference observed in HCC.
PMID- 26439985
TI - B5, a thioredoxin reductase inhibitor, induces apoptosis in human cervical cancer
cells by suppressing the thioredoxin system, disrupting mitochondrion-dependent
pathways and triggering autophagy.
AB - The synthetic curcumin analog B5 is a potent inhibitor of thioredoxin reductase
(TrxR) that has potential anticancer effects. The molecular mechanism underlying
B5 as an anticancer agent is not yet fully understood. In this study, we report
that B5 induces apoptosis in two human cervical cancer cell lines, CaSki and
SiHa, as evidenced by the downregulation of XIAP, activation of caspases and
cleavage of PARP. The involvement of the mitochondrial pathway in B5-induced
apoptosis was suggested by the dissipation of mitochondrial membrane potential
and increased expression of pro-apoptotic Bcl-2 family proteins. In B5-treated
cells, TrxR activity was markedly inhibited with concomitant accumulation of
oxidized thioredoxin, increased formation of reactive oxygen species (ROS), and
activation of ASK1 and its downstream regulatory target p38/JNK. B5-induced
apoptosis was significantly inhibited in the presence of N-acetyl-l-cysteine.
Microscopic examination of B5-treated cells revealed increased presence of
cytoplasmic vacuoles. The ability of B5 to activate autophagy in cells was
subsequently confirmed by cell staining with acridine orange, accumulation of LC3
II, and measurement of autophagic flux. Unlike B5-induced apoptosis, autophagy
induced by B5 is not ROS-mediated but a role for the AKT and AMPK signaling
pathways is implied. In SiHa cells but not CaSki cells, B5-induced apoptosis was
promoted by autophagy. These data suggest that the anticarcinogenic effects of B5
is mediated by complex interplay between cellular mechanisms governing redox
homeostasis, apoptosis and autophagy.
PMID- 26439987
TI - MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer
cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular
senescence.
AB - Among a number of non-coding RNAs, role of microRNAs (miRNAs) in cancer cell
proliferation, cancer initiation, development and metastasis have been
extensively studied and miRNA based therapeutic approaches are being pursued.
Prostate cancer (PCa) is a major health concern and several deregulated miRNAs
have been described in PCa. miR-212 is differentially modulated in multiple
cancers however its function remains elusive. In this study, we found that miR
212 is downregulated in PCa tissues when compared with benign adjacent regions (n
= 40). Also, we observed reduced levels of circulatory miR-212 in serum from PCa
patients (n = 40) when compared with healthy controls (n = 32). Elucidating the
functional role of miR-212, we demonstrate that miR-212 negatively modulates
starvation induced autophagy in PCa cells by targeting sirtuin 1 (SIRT1).
Overexpression of miR-212 also leads to inhibition of angiogenesis and cellular
senescence. In conclusion, our study indicates a functional role of miR-212 in
PCa and suggests the development of miR-212 based therapies.
PMID- 26439990
TI - Unilateral ventral strabismus in an aquarium Silver Arowana (Osteoglossum
bicirrhosum).
AB - An adult silver arowana (Osteoglossum bicirrhosum) presented with a 2-month
history of acute onset ventral strabismus of the right eye associated with a
cystic structure overlying the dorsal aspect of the globe. Aspiration of the
cyst, removal of redundant conjunctival tissue, and apposition of the surgical
edges of the conjunctiva did not correct the strabismus. Magnetic resonance
imaging of the head and histopathology of the eye did not reveal significant
differences between affected and unaffected eyes except for a more posterior
dorsal rectus muscle insertion site in the affected eye. This case report
documents and describes a syndrome well known among arowana hobbyists as 'drop
eye'.
PMID- 26439988
TI - OX40 expression enhances the prognostic significance of CD8 positive lymphocyte
infiltration in colorectal cancer.
AB - BACKGROUND: OX40 is a TNF receptor family member expressed by activated T cells.
Its triggering by OX40 ligand promotes lymphocyte survival and memory generation.
Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in
cancer immunotherapy. We explored the prognostic significance of tumor
infiltration by OX40+ cells in a large colorectal cancer (CRC) collective.
METHODS: OX40 gene expression was analyzed in 50 freshly excised CRC and
corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657
clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3
mAbs by standard immunohistochemistry. The CRC cohort was randomly split into
training and validation sets. Correlations between CRC infiltration by OX40+
cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical
pathological data and overall survival were comparatively evaluated. RESULTS:
OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene
expression. High CRC infiltration by OX40+ cells was significantly associated
with favorable prognosis in training and validation sets in univariate, but not
multivariate, Cox regression analysis. CRC with OX40(high)/CD8(high) infiltration
were characterized by significantly prolonged overall survival, as compared to
tumors with OX40(low)/CD8(high), OX40(high)/CD8(low) or OX40(low)/CD8(low)
infiltration in both uni- and multivariate analysis. In contrast, prognostic
significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined
evaluation. Irrespective of TNM stage, CRC with OX40(high)/CD8(high) density
infiltrates showed an overall survival similar to that of all stage I CRC
included in the study. CONCLUSIONS: OX40(high)/CD8(high) density tumor
infiltration represents an independent, favorable, prognostic marker in CRC with
an overall survival similar to stage I cancers.
PMID- 26439989
TI - Antitumoral activity of the mithralog EC-8042 in triple negative breast cancer
linked to cell cycle arrest in G2.
AB - Triple negative breast cancer (TNBC) is an aggressive form of breast cancer.
Despite response to chemotherapy, relapses are frequent and resistance to
available treatments is often observed in the metastatic setting. Therefore,
identification of new therapeutic strategies is required. Here we have
investigated the effect of the mithramycin analog EC-8042 (demycarosil-3D-beta-D
digitoxosyl mithramycin SK) on TNBC. The drug caused a dose-dependent inhibition
of proliferation of a set of TNBC cell lines in vitro, and decreased tumor growth
in mice xenografted with TNBC cells. Mechanistically, EC-8042 caused an arrest in
the G2 phase of the cell cycle, coincident with an increase in pCDK1 and Wee1
levels in cells treated with the drug. In addition, prolonged treatment with the
drug also causes apoptosis, mainly through caspase-independent routes.
Importantly, EC-8042 synergized with drugs commonly used in the therapy of TNBC
in vitro, and potentiated the antitumoral effect of docetaxel in vivo. Together,
these data suggest that the mithralog EC-8042 exerts an antitumoral action on
TNBC cells and reinforces the action of standard of care drugs used in the
therapy of this disease. These characteristics, together with a better toxicology
profile of EC-8042 with respect to mithramycin, open the possibility of its
clinical evaluation.
PMID- 26439992
TI - HORSE SPECIES SYMPOSIUM: Developmental programming: Applications in the horse.
PMID- 26439991
TI - Chemopreventive effect of leflunomide against Ehrlich's solid tumor grown in
mice: Effect on EGF and EGFR expression and tumor proliferation.
AB - i) AIMS: The current study aimed to examine the effect of leflunomide on tumoral
expression of epidermal growth factor and its receptor (EGFR) in Ehrlich's
ascites carcinoma (EAC) grown in mice. ii) MATERIALS AND METHODS: Mice were
injected subcutaneously with EAC cells and allocated into four groups; Group i:
EAC control group. Groups ii-iv: mice treated with leflunomide (3, 10 or
30mg/kg/day, p.o.), respectively. Pharmacologic treatments were initiated at day
8 and continued for 14days. iii) KEY FINDINGS: Treatment with leflunomide evoked
antitumor properties as indicated by reduction in tumor mass, histopathological
score, number of intratumoral PCNA immunopositive nuclei. Leflunomide (3, 10 or
30mg/kg) exerted an anti-inflammatory effect as indicated by the reduction in
serum tumor necrosis factor-alpha. Furthermore, leflunomide demonstrated anti
angiogenic activity which was expressed as a decline in serum vascular
endothelial growth factor and down-regulation of intratumoral EGF protein and
mRNA expression as well as EGFR expression in addition to suppression of
immunostaining for the endothelial marker, CD31. iv) SIGNIFICANCE: Taken
together, the present results demonstrated that leflunomide possessed anti
angiogenic and anti-proliferative activity against EAC solid tumors that might be
correlated to down regulation of EGF and EGFR. Further, the current data
indicated that leflunomide may have utility in the management of human cancer.
PMID- 26439993
TI - HORSE SPECIES SYMPOSIUM: Glucocorticoid programming of hypothalamic-pituitary
adrenal axis and metabolic function: Animal studies from mouse to horse.
AB - Adrenal glucocorticoids, such as cortisol, are essential for normal fetal
development and for maintaining homeostasis in adults. Developmental studies in
humans and other animals have shown that exposure to excess glucocorticoids
during critical windows of perinatal development can program permanent changes in
hypothalamic-pituitary-adrenal (HPA) axis function and metabolic function, with
adverse implications for the long-term health of the exposed offspring. The
current review compares the programming of postnatal HPA axis function and
glucose homeostasis among different species overexposed perinatally to
glucocorticoids, with emphasis on the horse. The potential role of epigenetic
modification of genes involved in the regulation of HPA axis and metabolic
function at cellular and molecular levels is also discussed.
PMID- 26439994
TI - HORSE SPECIES SYMPOSIUM: Nutritional programming and the impact on mare and foal
performance.
AB - Many environmental factors can alter the phenotype of offspring when applied
during critical periods of early development. In most domestic species, maternal
nutrition influences fetal development and the fetus is sensitive to the
nutrition of the dam during pregnancy. Many experimental models have been
explored including both under- and overnutrition of the dam. Both nutritional
strategies have yielded potential consequences including altered glucose
tolerance, pancreatic endocrine function, insulin sensitivity, body composition,
and colostrum quality. Although the impact of maternal nutrition on fetal
development in the equine has not been thoroughly investigated, overnutrition is
a common occurrence in the industry. Work in our laboratory has focused on
effects of maternal overnutrition on mare and foal performance, mare DMI, foaling
parameters, colostrum quality and passive transfer of immunity, and glucose and
insulin dynamics. Over several trials, mares were fed either 100 or 140% of NRC
requirements for DE, and supplemental Se and arginine were added to diets in an
attempt to mitigate potential intrauterine growth retardation resulting from dams
overfed during the last third of pregnancy. As expected, when mares were overfed,
BW, BCS, and rump fat values increased. Foal growth over 150 d was also not
influenced. Maternal nutrition did not alter colostrum volume but influenced
colostrum quality. Maternal overnutrition resulted in lower colostrum IgG
concentrations but did not cause failure of passive transfer in foals.
Supplemental Se and arginine were unable to mitigate this reduction in colostrum
IgG. Additionally, mare and foal glucose and insulin dynamics were influenced by
maternal nutrition. Mare glucose and insulin area under the curve (AUC) increased
with increased concentrate supplementation. Foal insulin AUC and peak insulin
concentrations were increased when mares were fed concentrate and, in a later
trial, foal peak glucose values were reduced with arginine supplementation of the
mare. This influence of maternal nutrition on glucose and insulin dynamics
warrants further investigation because it may be related to athletic performance
and metabolic disease in the adult. Further studies will be necessary to fully
elucidate the influence of mare nutrition during pregnancy on development of the
fetus as well as long-term consequences of developmental programming.
PMID- 26439995
TI - Genetic analysis and genomic selection of stayability and productive life in New
Zealand ewes.
AB - Genetic parameters for ewes were estimated for stayability (STAY) and productive
life (Prodlife). Records from 658,871 animals from 241 seed stock or ram breeder
flocks and one research flock were used to estimate parameters for ram breeder
flock STAY and Prodlife. These flocks would have a culling policy based on
criteria typical of a commercial enterprise, but including culls based on
knowledge such as estimated breeding values. A subset of 35,688 of these animals
from 4 ram breeder and one research flock was used to infer the animals that
might be culled based on the perspective of a commercial flock as these flocks
recorded reasons for culling. These data were used to estimate parameters for
commercial flock STAY and Prodlife. Heritability for ram breeder flock STAY until
age 3 to 6 yr ranged from 0.07 to 0.09. The heritability of commercial flock STAY
was similar in yr 5 and 6, but lower at 0.05 (age 3) and 0.07 (age 4).
Heritability of Prodlife for ram breeder flock and commercial flock was
respectively 0.10 and 0.13. The genetic correlations between ram breeder flock
STAY and commercial flock STAY ranged from 0.20 to 0.99. Both STAY and Prodlife
were most correlated genetically with the trait number of lambs born, at about
0.4, and to a lesser degree, live weight up to the age of 12 mo for the traits
analyzed with lower genetic correlations estimated for the commercial flocks.
Live weight at 18 mo and fleece weight had little or no correlation with STAY and
Prodlife. From the data set used to estimate genetic parameters from a ram
breeder flock, 4,330 animals were genotyped with the Illumina OvineSNP50 BeadChip
and the genotypes used to develop genomic predictions via genomic best linear
unbiased prediction. The animals used in the training data set were multibreed,
but were heavily Romney breed based. The genomic prediction accuracy for ram
breeder flock STAY, according to breed, was dependent on sample size and ranged
from 0.4 to 0.44 for Romney and 0.26 to 0.4 for Coopworth. Accuracies for
Perendale and Composites, for which sample sizes were less, were more variable.
This study has derived genetic parameters for STAY and Prodlife and investigated
genomic predictions for these traits. As these traits are of low heritability,
sex limited and expressed late in life genomic selection will be useful.
PMID- 26439996
TI - Comparison of serum biochemical parameters between two broiler chicken lines
divergently selected for abdominal fat content.
AB - In humans, obesity is associated with increased or decreased levels of serum
biochemical indicators. However, the relationship is not as well understood in
chickens. Due to long-term intense selection for fast growth rate, modern
broilers have the problem of excessive fat deposition, exhibiting biochemical or
metabolic changes. In the current study, the Northeast Agricultural University
broiler lines divergently selected for abdominal fat content (NEAUHLF) were used
to identify differences in serum biochemical parameters between the 2 lines. A
total of 18 serum biochemical indicators were investigated in the 16th, 17th, and
18th generation populations of NEAUHLF, and the genetic parameters of these serum
biochemical indicators were estimated. After analyzing the data from these 3
generations together, the results showed that the levels of 16 of the tested
serum biochemical parameters were significantly different between the lean and
fat birds. In the fat birds, serum concentrations of high-density lipoprotein
cholesterol (HDL-C), HDL-C:low-density lipoprotein cholesterol (LDL-C), total
bile acid, total protein, albumin, globulin, aspartate transaminase (AST):alanine
transaminase (ALT), gamma-glutamyl transpeptidase (GGT), uric acid, and
creatinine were very significantly higher (P < 0.01), whereas LDL-C,
albumin:globulin, glucose, AST, ALT, and free fatty acids concentrations in serum
were very significantly lower than those in the lean birds (P < 0.01). Of these
16 serum biochemical parameters, 5 (LDL-C, HDL-C:LDL-C, total bile acid, albumin,
and albumin:globulin) had high heritabilities (0.58 <= h2 <= 0.89), 6 (HDL-C,
total protein, globulin, AST:ALT, GGT, and creatinine) had moderate
heritabilities (0.29 <= h2 <= 0.48), and the remaining 5 had low heritabilities
(h2 < 0.20). Serum HDL-C, HDL-C:LDL-C, and glucose had higher positive genetic
correlation coefficients (rg) with abdominal fat traits (0.30 <= rg <= 0.80),
whereas serum globulin, AST, and uric acid showed higher negative genetic
correlations with abdominal fat traits (-0.62 <= rg <= -0.30). The remaining 10
serum biochemical parameters had lower genetic correlations with abdominal fat
traits (-0.30 < rg < 0.30). In conclusion, we identified serum HDL-C and HDL
C:LDL-C levels as potential biomarkers for selection of lean birds. These
findings will also be useful in future studies for investigating obesity and
lipid metabolism in humans as well as in other animal species.
PMID- 26439997
TI - Estimates of genetic parameters for reproductive traits in Brahman cattle breed.
AB - This study was designed to estimate genetic parameters for the following traits
of Brahman cattle in Brazil: age at first calving (AFC), calving interval (CI),
rebreeding (REB), and stayability (STAY). For REB, the value 1 was assigned to
heifers that rebred and calved after first calving and the value 0 was assigned
to heifers that failed to rebreed after first calving. Likewise, for STAY, the
value 1 was assigned to cows that calved at least 3 times by the time they reach
6 yr of age; otherwise, the value 0 was assigned. A bivariate analysis was used
to estimate covariances components by using linear animal model for CI and AFC
and threshold animal model for REB and STAY. The mean h(2) were 0.10, 0.02, 0.22,
and 0.10 for AFC, CI, REB, and STAY, respectively. The genetic correlations were
0.13 between AFC and CI, -0.35 between AFC and REB, -0.57 between AFC and STAY,
and 0.32 between REB and STAY, which reveal that cows that remain productive for
longer periods in the herd also start breeding younger and present greater
chances to REB. The selection of Brahman cattle for reproductive traits, such as
AFC, CI, REB, and STAY, will render low magnitude and long-term responses.
PMID- 26439998
TI - Identification of signatures of selection for intramuscular fat and backfat
thickness in two Duroc populations.
AB - Intramuscular fat (IMF) content is an important trait affecting the quality of
pork. Two Duroc populations, one under positive selection for IMF and the other
selected for decreased backfat but under stabilizing selection for IMF, were used
to identify signatures of selection associated with IMF using 60,000 single
nucleotide polymorphism data. The effects of selection were analyzed between 2
lines or groups representing selected and control animals within each population
using a discriminant analysis of principal components and Wright's fixation index
(FST). Moreover, extended haplotype homozygosity-based approaches were used to
examine the changes in haplotype frequency due to recent selection. Each
statistical method identified 10-20 selection signatures. A few haplotype-based
signatures of selection agreed with results from a genome-wide association study
(GWAS), while FST measures showed a better agreement with GWAS results. Agreement
of marker-trait associations and signatures of selection was limited, and further
examination will be necessary to understand the effect of selection on IMF and
why some regions identified by GWAS did not appear to respond to the selection
practiced. The genes in 21 consensus selection signatures were examined. Several
genes with an effect on overall fatness were identified, but further research is
needed to assess whether or not some of them could have a specific effect on IMF.
PMID- 26439999
TI - Genetic associations of short- and long-term aggressiveness identified by skin
lesion with growth, feed efficiency, and carcass characteristics in growing pigs.
AB - The objective of this study was to investigate the genetic relationships between
skin lesion traits in group housed growing pigs as a measure of short- (in a
newly mixed group) and long- (in a socially stable group) term aggression and
commonly used commercial performance measures: growth, feed intake, feed
efficiency, and carcass traits. Data on 2,413 growing pigs (138 groups) were
available. Pigs were mixed into new social groups of 18 animals, and skin lesions
were counted 24 h (SL24h) and 5 wk (SL5wk) postmixing. The animal model was used
to estimate genetic parameters for skin lesion traits, test daily gain, lifetime
daily gain, daily feed intake, feed efficiency (calculated as test daily gain
divided by daily feed intake), loin depth, back fat, and HCW. Skin lesions had a
heritable component, ranging from 0.08 for anterior SL24h to 0.22 for central
SL5wk and would, therefore, be suitable as a method of phenotyping aggression for
selection purposes. Significant positive genetic correlations were found between
SL24h and SL5wk (0.46 to 0.81). Positive genetic correlations were also found
between SL24h (central and posterior body regions) or SL5wk (all body regions)
and the production traits lifetime daily gain, test daily gain, and HCW (0.29 to
0.54). Central SL24h, anterior SL5wk, and posterior SL5wk were found to correlate
positively with feed efficiency (0.39 to 0.50), suggesting that pigs with more
lesions convert feed more efficiently. Where significant, the magnitude of
phenotypic correlations was low but positive (0.07 to 0.10). These results
suggest that, genetically, animals that receive many lesions show improved
performance compared to those with few lesions, except for anterior SL24h, which
had previously been shown to be genetically positively correlated with the
initiation of nonreciprocal attacks. It may, therefore, be possible, via
selection against anterior skin lesions at mixing, to reduce this form of 1-sided
aggression without adversely affecting production traits.
PMID- 26440000
TI - Accuracy of genomic prediction using deregressed breeding values estimated from
purebred and crossbred offspring phenotypes in pigs.
AB - Genomic selection is applied to dairy cattle breeding to improve the genetic
progress of purebred (PB) animals, whereas in pigs and poultry the target is a
crossbred (CB) animal for which a different strategy appears to be needed. The
source of information used to estimate the breeding values, i.e., using
phenotypes of CB or PB animals, may affect the accuracy of prediction. The
objective of our study was to assess the direct genomic value (DGV) accuracy of
CB and PB pigs using different sources of phenotypic information. Data used were
from 3 populations: 2,078 Dutch Landrace-based, 2,301 Large White-based, and 497
crossbreds from an F1 cross between the 2 lines. Two female reproduction traits
were analyzed: gestation length (GLE) and total number of piglets born (TNB).
Phenotypes used in the analyses originated from offspring of genotyped
individuals. Phenotypes collected on CB and PB animals were analyzed as separate
traits using a single-trait model. Breeding values were estimated separately for
each trait in a pedigree BLUP analysis and subsequently deregressed. Deregressed
EBV for each trait originating from different sources (CB or PB offspring) were
used to study the accuracy of genomic prediction. Accuracy of prediction was
computed as the correlation between DGV and the DEBV of the validation
population. Accuracy of prediction within PB populations ranged from 0.43 to 0.62
across GLE and TNB. Accuracies to predict genetic merit of CB animals with one PB
population in the training set ranged from 0.12 to 0.28, with the exception of
using the CB offspring phenotype of the Dutch Landrace that resulted in an
accuracy estimate around 0 for both traits. Accuracies to predict genetic merit
of CB animals with both parental PB populations in the training set ranged from
0.17 to 0.30. We conclude that prediction within population and trait had good
predictive ability regardless of the trait being the PB or CB performance,
whereas using PB population(s) to predict genetic merit of CB animals had zero to
moderate predictive ability. We observed that the DGV accuracy of CB animals when
training on PB data was greater than or equal to training on CB data. However,
when results are corrected for the different levels of reliabilities in the PB
and CB training data, we showed that training on CB data does outperform PB data
for the prediction of CB genetic merit, indicating that more CB animals should be
phenotyped to increase the reliability and, consequently, accuracy of DGV for CB
genetic merit.
PMID- 26440001
TI - Strong connectedness within Norwegian Cheviot and Fur Sheep ram circles allows
reliable estimation of breeding values.
AB - Breeding programs for sheep in Norway are based on cooperatives of ram circles
(RC). The key features of RC are selection of rams across member flocks and their
rotation among RC flocks during the mating season. Genetic gains are disseminated
to flocks outside RC (ORC). In both groups, natural service and AI are practiced.
The objectives were to investigate 1) connectedness within and across RC and
across RC and ORC, which impacts bias in genetic comparisons across flocks, and
2) opportunities to improve accuracy by including data from ORC flocks in genetic
evaluation of RC flocks. Weaning weights in Cheviot and Fur Sheep from 1990 to
2010 were used. In Cheviot, in the last year of data (2010), there were 4 RC with
49 flocks and 1,824 ewes. Seventy-seven ORC flocks, with 1,246 ewes, also were
recorded that year. In total, 214,391 pedigree and 131,012 performance records in
Cheviot were available. For Fur Sheep, there was 1 RC with 8 flocks and 468 ewes
in 2010 and 134 ORC flocks with 1,932 ewes. In total, 198,339 pedigree and
110,955 performance records in Fur Sheep were available. Unbiased comparison of
EBV requires that genetic means of flock founders are similar or that flocks are
genetically connected. The latter requires that rams sire enough progeny across
flocks. In RC in both breeds and in 28.6% of Cheviot and 20% of Fur Sheep ORC
flocks, the average prediction error correlation of flock mean EBV (flock rij)
exceeded a threshold (0.10) for strong connectedness. These flocks also had
similar genetic means: the variance between means of flock founders (genetic
groups) was 1.05 (Cheviot) and 0.51 (Fur Sheep) times that of the additive
variance for weaning weight. With less connected flocks included (flock rij <=
0.10), the between genetic group variance increased to 1.6 times the additive
variance. When weaning weights from connected ORC flocks were included in the
genetic evaluation of RC flocks, the size of the data increased by 1.07 times in
Cheviot and by 3.6 times in Fur Sheep. However, the increase in accuracy of EBV
of animals in RC flocks was trivial. Because founder animals of RC flocks had
similar genetic means and were strongly connected, flock owners can comfortably
focus on other aspects of their breeding program. Opportunities for closer
cooperation between RC and connected ORC flocks exist and could be explored to
accelerate genetic improvement within the Norwegian Cheviot and Fur Sheep breeds.
PMID- 26440002
TI - Transcriptomic analysis by RNA sequencing reveals that hepatic interferon-induced
genes may be associated with feed efficiency in beef heifers.
AB - In beef cattle, production feedstuffs are the largest variable input cost. Beef
cattle also have a large carbon footprint, raising concern about their
environmental impact. Unfortunately, only a small proportion of dietary energy is
directed toward protein deposition and muscle growth whereas the majority
supports body maintenance. Improving feed efficiency would, therefore, have
important consequences on productivity, profitability, and sustainability of the
beef industry. Various measures of feed efficiency have been proposed to improve
feed utilization, and currently, residual feed intake (RFI) is gaining
popularity. However, the cost associated with measuring RFI and the limited
knowledge of the biology underlying improved feed efficiency make its adoption
prohibitive. Identifying molecular mechanisms explaining divergence in RFI in
beef cattle would lead to the development of early detection methods for the
selection of more efficient breeding stock. The objective of this study was to
identify hepatic markers of metabolic feed efficiency in replacement beef
heifers. A group of 87 heifers were tested for RFI adjusted for off-test backfat
thickness (RFIfat). Preprandial liver biopsies were collected from 10 high- and
10 low-RFIfat heifers (7 Hereford-Aberdeen Angus and 3 Charolais-Red Angus-Main
Anjou per group) and gene expression analysis was performed using RNA sequencing
and quantitative real-time PCR. The heifers used in this study differed in RFIfat
averaging 0.438 vs. -0.584 kg DM/d in high- and low-RFIfat groups, respectively.
As expected, DMI was correlated with RFIfat and ADG did not differ between high-
and low-RFIfat heifers. Through a combination of whole transcriptome and
candidate gene analyses, we identified differentially expressed genes involved in
inflammatory processes including hemoglobin beta (HBB), myxovirus resistance 1
interferon-inducible protein p78 (MX1), ISG15 ubiquitin-like modifier (ISG15),
hect domain and RLD 6 (HERC6), and interferon-induced protein 44 (IFI44) whose
mRNA abundance was lower (HBB) or higher (MX1, ISG15, HERC6, and IFI44) in low
RFIfat heifers. These genes have been shown to be directly or indirectly
modulated by interferon signaling and involved with innate immunity. Our results
suggest that more efficient heifers respond differently to hepatic
proinflammatory stimulus, potentially expending less energy toward combating
systemic inflammation and redirecting nutrients toward growth and protein
accretion.
PMID- 26440003
TI - High dietary selenium and vitamin E supplementation ameliorates the impacts of
heat load on oxidative status and acid-base balance in sheep.
AB - The objective of this study was to determine the efficacy of supranutritional
dietary selenium and vitamin E (Vit E) to ameliorate the effect of heat stress
(HS) on oxidative status and acid-base balance in sheep. Thirty-two Merino * Poll
Dorset ewes were acclimated to indoor individual pen feeding of a pelleted
control diet (0.24 g Se and 10 IU of Vit E/kg DM) for 1 wk. Sheep were then moved
to metabolism cages in climatic chambers and randomly allocated to a 2 * 2 * 2
factorial design with the respective factors being dietary Se (0.24 and 1.20
mg/kg DM as Sel-Plex; Alltech, Australia), Vit E (10 and 100 IU/kg DM), and
temperature for 2 wk. After 1 wk of acclimation in metabolic cages, 1 climatic
chamber continued on thermoneutral (TN) conditions (18 degrees C to 21 degrees C
and 40% to 50% relative humidity [RH]), and the other one was set to HS
conditions (28 degrees C to 40 degrees C and 30% to 40% RH) for 1 wk. The sheep
were then returned to individual pens and fed the control diet for 1 wk before
being returned to the same diet as in the first period but a reversed thermal
treatment for a further 2 wk. Physiological parameters were recorded 3 times
daily, and blood samples were collected on d 1 and 7 of thermal treatment.
Average respiration rate and rectal temperature of sheep were increased (P <
0.001) during HS; however, combined supranutritional supplementation of Se and
Vit E reversed the effects of HS. Sheep given the high Se and high Vit E diet had
a lower respiration rate (191 vs. 232 breaths/min; P = 0.012) and rectal
temperature (40.33 degrees C vs. 40.58 degrees C; P = 0.039) under peak HS (1700
h) compared with those fed the low Se and low Vit E diet. Plasma reactive oxygen
metabolites concentrations were reduced (P = 0.048) by 20%, whereas biological
antioxidant potential was increased (P = 0.17) by 10% in sheep fed the high Se
and high Vit E diet compared with those fed the low Se and low Vit E diet. Blood
pH was elevated (P = 0.007) and bicarbonate was reduced (P = 0.049) under HS, and
again, these effects were ameliorated by the high Se and high Vit E diet. Both
white blood cell glutathione peroxidase gene expression and red blood cell lysate
glutathione peroxidase activity were increased in sheep fed the high Se and high
Vit E diet. These data suggest that supranutritional dietary Se or Vit E can
reduce some of the negative effects of HS. However, the synergism between the 2
antioxidants improves their potential to ameliorate the impacts of HS in sheep.
PMID- 26440004
TI - Dietary chromium methionine supplementation could alleviate immunosuppressive
effects of heat stress in broiler chicks.
AB - The present study was conducted to investigate the effects of dietary
supplementation of chromium methionine (CrMet) on performance, immune responses,
and stress status of broiler chicks subjected to heat-stress conditions. A total
of 450 day-old Ross 308 broiler chicks were randomly distributed between 5
replicate pens (15 birds each) of 6 experimental treatments according to a 2 * 3
factorial arrangement of treatments including 2 temperature conditions
(thermoneutral and heat stress) and 3 supplemental Cr levels (0, 500, and 1,000
MUg/kg as CrMet). For induction of heat stress, the house temperature was set at
35 +/- 2 degrees C from 15 to 42 d of age. Results showed that the chicks
subjected to heat-stress condition had lower (P < 0.01) feed intake, BW gain, and
deteriorated (P < 0.05) feed conversion values compared with those kept in the
thermoneutral house. Dietary supplementation with CrMet increased (P < 0.01) feed
intake and improved (P < 0.01) weight gain and feed efficiency. There were
significant Cr level * temperature interactions, so that inclusion of CrMet into
the diets was more effective in heat-stressed chicks. Exposure to heat stress
suppressed (P < 0.01) cutaneous hypersensivity response to phytohemagglutinin-P
injection at 30 d of age, and dietary supplementation of 500 MUg Cr/kg induced (P
< 0.05) this response, with the greater impacts in heat-stressed chicks,
resulting in a significant (P < 0.01) Cr * temperature interaction. Antibody
responses against Newcastle and infectious bronchitis disease viruses were
diminished (P < 0.01) in heat-stressed chicks. Dietary inclusion of CrMet
improved (P < 0.05) antibody responses to different immunostimulants, and this
effect was more pronounced in heat-stressed chicks. Exposure to heat stress
caused a significant (P < 0.05) decrease in the proportion of helper (CD4+) T
lymphocytes and increased cytotoxic (CD8+) T lymphocytes, resulting in a
decreased (P < 0.01) CD4+ to CD8+ ratio in peripheral blood circulation.
Supplementation of CrMet to heat-stressed chicks modulated (P < 0.01) plasma
corticosterone level. The present findings indicate that dietary CrMet
supplementation could alleviate heat-stress-induced growth retardation in broiler
chicks. Moreover, supplemental CrMet modulated suppressive effects of heat stress
on cellular and humoral immune responses.
PMID- 26440005
TI - Equine endometrial gene expression changes during and after maternal recognition
of pregnancy.
AB - The mechanism for maternal recognition of pregnancy (MRP) in horses is unknown.
To maintain a pregnancy, a mobile conceptus must be recognized by the uterus
before d 14 postovulation (PO). This recognition prevents endometrial secretion
of PGF2alpha on d14 through 16, which would otherwise initiate luteolysis. The
objective of this study was to evaluate gene expression in the endometrium of
pregnant and nonpregnant mares during and after MRP to identify possible genes
involved during this time. Twelve normally cycling mares were used in a crossover
design and randomly assigned to a specific collection day. Endometrial samples
were collected from a pregnant and nonpregnant (nonmated) mare on cycle d 12, 14,
16, and 18 (n = 3/d) PO. Microarray analysis comparing the endometrial gene
expression in pregnant and nonpregnant mares revealed no differences at d 12. Ten
genes were identified to have consistently higher or lower expression levels in
the endometrium from pregnant versus nonpregnant mares on d 14, 16, and 18 (P <
0.001). The expression of these 10 genes was further analyzed with real-time PCR.
d 14, 16, and 18 gene expression patterns were consistent with the microarray
analysis, but on d 12, 4 of the 10 were identified as differentially expressed.
Endometrial samples were then collected on d 13 PO (n = 3) and processed for
western blot and immunohistochemical analysis of 2 proteins due to their
reproductive significance. SPLA2 and DKK1 antibody specificity were confirmed via
western blot analysis but were not different in samples from pregnant and
nonpregnant mares (P = 0.114 and P = 0.514, respectively) and cellular
localization was examined by immunohistochemical analysis. This is the first
study to describe gene expression and cellular localization in the endometrium at
the time of MRP for these genes and suggests that the uterus does not prepare to
support a pregnancy until d 14. The function of these genes may be critical in
the process of MRP.
PMID- 26440006
TI - Postprandial glucose, insulin, and glucagon-like peptide-1 responses of different
equine breeds adapted to meals containing micronized maize.
AB - The enteroinsular axis is a complex system that includes the release of incretin
hormones from the gut to promote the absorption and utilization of glucose after
a meal. The insulinogenic effect of incretin hormones such as glucagon-like
peptide-1 (GLP-1) remains poorly characterized in the horse. The aim of this
study was to compare postprandial glucose, insulin, and GLP-1 responses of
different equine breeds adapted to twice-daily meals containing micronized maize.
Four Standardbred horses, 4 mixed-breed ponies, and 4 Andalusian cross horses in
moderate BCS (5.5 +/- 0.2 out of 9) were fed meals at 0800 and 1600 h each day.
The meals contained micronized maize (mixed with soaked soybean hulls and lucerne
chaff), with the amount of maize gradually increased over 12 wk to reach a final
quantity of 1.7 g/kg BW (1.1 g/kg BW starch) in each meal. Animals had ad libitum
access to the same hay throughout. After 12 wk of acclimation, serial blood
samples were collected from all animals over a 14-h period to measure
concentrations of glucose, insulin, and GLP-1, with meals fed immediately after
the 0 and 8 h samples. Glucose area under the curve (AUC) values were similar
between breed groups (P = 0.41); however, ponies and Andalusian horses exhibited
significantly higher insulin AUC values after both meals compared with
Standardbred horses (both P < 0.005). Postprandial GLP-1 AUC values were also
significantly higher in ponies and Andalusian horses compared with Standardbred
horses (breed * time interaction; P < 0.001). Correlation analysis demonstrated a
strong positive association between concentrations of insulin and GLP-1 over time
(rs = 0.752; P < 0.001). The increased insulin concentrations in ponies and
Andalusian horses may partly reflect lower insulin sensitivity but could also be
attributed to increased GLP-1 release. Given that hyperinsulinemia is a
recognized risk factor for the development of laminitis in domestic equids, this
study provides evidence that the enteroinsular axis warrants further
investigation.
PMID- 26440007
TI - The effect of Bacillus coagulans-fermented and nonfermented Ginkgo biloba on the
immunity status of broiler chickens.
AB - To evaluate and compare the effects of Bacillus coagulans-fermented Ginkgo biloba
(FG) and nonfermented Ginkgo biloba (NFG) on the immunity status of broiler
chickens, 180 1-d-old female Arbor Acres chicks were divided into 3 groups and
fed either a basal diet, a basal diet supplemented with 0.3% NFG, or a basal diet
supplemented with 0.3% FG. Blood samples were taken on the seventh (before
vaccination), 14th, 21st, 28th and 35th day for the assessment of serum IL-18 and
interferon gamma (IFN-gamma) levels by ELISA. In addition, Newcastle disease
antibody titer analysis was made via hemagglutination and hemagglutination
inhibition test methods. On d 35, 6 chickens from each group were sacrificed and
the thymus, liver, spleen, small intestine (jejunum segment), cecum, and bursa of
Fabricius from each chicken were removed for analysis. RNA was isolated for
defensin expression detection by real-time PCR (q-PCR). The results showed that
serum IL-18 and IFN-gamma levels decreased after treatment with NFG and FG
compared with untreated control chickens. The ND antibody titers did not differ
significantly between the 3 groups on the seventh, 14th, 21st and 28th day;
however, on the 35th day, the ND antibody titers of the NFG and FG chickens were
both significantly higher than those of control group chickens. Defensin RNA
expression levels were inhibited by NFG; however, they were induced by FG. In
conclusion, fermentation of Ginkgo biloba with Bacillus coagulans can promote the
beneficial effect of Gingko biloba on the immunity status of broiler chickens.
PMID- 26440008
TI - Cortisol secretion in response to metabolic and inflammatory challenges in dairy
cows.
AB - Cortisol in dairy cows is released in an episodic manner underlying a circadian
rhythm. The involvement of cortisol in numerous adaptive processes to cope with
adverse conditions such as pain and inflammation is well characterized. Recent
studies described contradictory effects of nutrition and metabolism on the
secretory pattern of cortisol. However, up to now, the direct effects of single
metabolites during various metabolic conditions without the profound endocrine
changes around parturition on the glucocorticoid secretion in dairy cows have not
been described. The objective of this study was to investigate the effects of
long-term (56-h) manipulated metabolic states, that is, manipulated plasma
concentrations of glucose and beta-hydroxybutyrate (BHBA), on the release of
cortisol in midlactation dairy cows. Besides the concentration of cortisol at
defined time points, its pulsatile secretory pattern was studied in combination
with an acute immune challenge through an intramammary lipopolysaccharide (LPS)
challenge. Twenty-five midlactation dairy cows were randomly assigned to 1 of 4
treatments (hyperinsulinemic hypoglycemic clamp [HypoG], hyperinsulinemic
euglycemic clamp [EuG], continuous infusion of BHBA [HyperB], or infusion of
saline solution for the control group [Control). Different metabolic states
induced by infusion treatments affected the characteristics of cortisol secretion
(elevation of baseline [the HypoG and HyperB treatments] and decreased peak
length [the HypoG treatment]; P < 0.05), whereas amplitude, peak interval,
height, peak area, area under the curve (AUC) above the baseline cortisol
concentration (AUCb), and the total AUC (AUCt) were not different between
infusion treatments. The induced inflammatory response due to the intramammary
LPS challenge at simultaneously maintained infusion treatments diminished the
pulsatile nature of cortisol release, whereas AUCb (and AUCt, respectively) was
lowest for the HypoG treatment compared with the HyperB and Control treatments (P
< 0.05). This study indicates that single metabolites (glucose and BHBA) and
their availability or turnover (in case of glucose) have a different impact on
the regulation of cortisol secretion resulting in changes of its pulsatile
release. Furthermore, cortisol release during intramammary inflammation was found
to be greater in the HyperB, EuG, and Control treatments compared with the HypoG
treatment (P < 0.05). This finding emphasizes the regulatory role of the current
metabolic status on the cortisol release during inflammation.
PMID- 26440009
TI - Net energy content of dry extruded-expelled soybean meal fed with or without
enzyme supplementation to growing pigs as determined by indirect calorimetry.
AB - Two experiments were conducted to determine the NE content of dry extruded
expelled soybean (DESBM) and the effect of a multienzyme carbohydrase (MC)
mixture on the NE content of DESBM and to determine the effect of diet design on
NE values in growing pigs using indirect calorimetry (IC). In Exp. 1, 24 barrows
(19.6 +/- 0.51 kg BW) were allotted in a completely randomized design to 4
dietary treatments: a corn-soybean meal basal diet (Diet A), a diet containing
Diet A and DESBM in an 80:20 ratio with a constant CP (Diet B), a diet with an
80:20 ratio of Diet A and DESBM with a constant corn:soybean meal ratio (Diet C),
and a diet with simple substitution of Diet A with DESBM in an 80:20 ratio (Diet
D). Pigs were fed in metabolism crates for a period of 16 d to determine the DE
and ME and thereafter were moved into an indirect calorimeter where O2
consumption and CO2 production were measured to determine heat production and
fasting heat production. The NE content of DESBM was calculated (difference
method) to be 2,632, 2,548 and 2,540 kcal/kg DM in diets B, C, and D,
respectively. Respective values obtained with published prediction equations were
2,624, 2,530 and 2,436 kcal/kg. In Exp. 2, 24 barrows (16.9 +/- 0.76 kg BW) were
randomly allotted to 1 of 4 treatments. The diets were a corn-soybean meal basal
diet and a diet containing the basal diet and DESBM in an 80:20 ratio with a
constant corn:soybean meal ratio with or without 2 levels (0.05% and 0.1%) of MC.
The experimental procedures were similar to those described in Exp. 1. Enzyme
supplementation improved (P < 0.0001) the DE, ME, and NE content of the DESBM.
Multienzyme carbohydrase at 0.05% and 0.1% of the diet improved NE values of
DESBM by 4.9% and 3.7%, respectively. In conclusion, the NE values of DESBM
obtained with the IC method were higher than the values obtained with prediction
equations; the disparity was least when diets were formulated with a constant CP
level. However, as the difference method was used to determine the NE of
ingredient, it is more appropriate to maintain a constant ratio between the
ingredients. Also, the NE value of DESBM obtained for diets C and D were not
different. Hence, the average NE value of DESBM evaluated was 2,544 kcal/kg DM.
Enzyme supplementation improved the NE content of DESBM fed to growing pigs.
PMID- 26440010
TI - Effects of feed additives on ileal mucosa-associated microbiota composition of
broiler chickens.
AB - The effects of dietary supplementation with 2 recently developed feed additives
on the composition of the mucosa-associated microbiota of the ileum were studied
in growing broiler chickens. A total of 48 male 1-d-old broiler chickens of the
Cobb 500 strain were distributed in 4 treatments with 2 replicates of 6 birds
each. The 2 additives tested were a di-d-fructose dianhydride-enriched caramel
(FC) and the garlic derivative propyl propane thiosulfonate (PTS-O). Dietary
treatments were a control (commercial diet with no additive), INU (20 g inulin/kg
diet), CAR (20 g FC/kg diet), and GAR (90 mgPTS-O/kg diet). As a result of this
study, inulin supplementation resulted in lower (P < 0.05) and FC feeding
resulted in higher (P < 0.05) Blautia coccoides/Eubacterium rectale log10 number
of copies respect to controls. Higher (P < 0.05) bifidobacteria log10 number of
copies with respect to the controls was determined in the ileal mucosa of birds
fed the PTS-O-supplemented diet. Denaturing gradient gel electrophoresis and PCR
analysis on Bifidobacterium spp. revealed the presence of Bifidobacterium longum,
Bifidobacterium pseudolongum, and Bifidobacterium pseudocatenulatum in samples
from chickens fed the control and the PTS-O-supplemented diet. Bifidobacterium
longum was exclusively found in poultry fed the control diet, whereas B.
pseudocatenulatum was found only in poultry fed the PTS-O-supplemented diet. This
study showed that both PTS-O and FC were able to modulate the composition of the
ileal mucosa-associated microbiota of growing broiler chickens. Finally, in
addition to B. pseudolongum, the presence of B. longum and B. pseudocatenulatum,
species not previously described in intestinal samples of broilers, was also
demonstrated.
PMID- 26440011
TI - Effects of zinc sulfate pretreatment on heat tolerance of Bama miniature pig
under high ambient temperature.
AB - The aim of this study was to evaluate the heat tolerance of Bama miniature pigs
under high ambient temperature (40 degrees C) and Zn interactive functions during
heat treatment (HT). Bama miniature pigs (male; n = 24; 6-mo old; BW = 10.79 +/-
0.06 kg) were randomly allotted to 4 groups and were fed a basal diet or the
basal diet supplemented with 1,500 mg of Zn (ZnSO4.H2O)/kg diet for 38 d. At 7 mo
of age (d 30), the thermal neutral (TN) groups remained at 25 degrees C, whereas
the HT groups were exposed to ambient temperature at 40 degrees C for 5 h daily
for 8 consecutive days. Pigs in 4 groups were sacrificed on d 38. Individual
rectal temperatures, skin temperatures, and breathing rates were recorded at 3 h
after the onset of HT and the blood samples were collected immediately after HT
on d 30, 34, and 38. Pigs fed diets with or without Zn doubled their breathing
rates (P < 0.05) and increased body surface, scrotal, and rectal temperatures
during HT on d 30, 34, and 38, respectively. Zinc supplementation increased BW
gain (BWG; P < 0.05) during 38-d experiment period, and HT decreased BWG only
from d 30 to 34 (P < 0.05). Heat treatment increased serum testosterone on d 30
(P < 0.05). Zinc supplementation decreased the heat-induced increase of
testosterone in HT on d 30 and 34 (P < 0.05). The relative weight of liver
increased in HT groups (P < 0.05). Zinc supplementation decreased the relative
weights of spleen (P < 0.05) and testis (P < 0.01). The values of abnormal
lymphocyte count and large unstained cell count declined approximately 5 times in
groups of Zn supplementation, whereas Zn supplementation increased the values of
red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, and mean
corpuscular hemoglobin. Zinc concentrations increased in serum, liver, kidney,
epididymis, longissimus, hair, and feces in groups fed with Zn (P < 0.01).
However, additional Zn decreased Zn concentrations in lung, spleen, and testis (P
< 0.01). Moreover, HT decreased serum Zn concentrations (P < 0.01). In
conclusion, Zn supplementation could be used to alleviate the decline of serum Zn
during periods of high ambient temperatures. However, pretreated supplementation
with pharmacological Zn did not promote heat tolerance but impacted the
erythropoiesis, immunity, and reproductive organ development in Bama miniature
pigs.
PMID- 26440013
TI - Effects of microbial phytase on the apparent and standardized total tract
digestibility of phosphorus in rice coproducts fed to growing pigs.
AB - The objectives of this experiment were to determine the apparent total tract
digestibility (ATTD) and the standardized total tract digestibility (STTD) of P
and the effect of microbial phytase on ATTD and STTD of P in full-fat rice bran
(FFRB), defatted rice bran (DFRB), brown rice, broken rice, and rice mill feed
when fed to pigs. Ninety-six barrows (initial BW of 19.4 +/- 1.4 kg) were
allotted to 12 diets with 8 replicate pigs per diet in a randomized complete
block design. A basal diet based on corn and soybean meal was formulated. Five
additional diets containing corn, soybean meal, and each rice coproduct were also
formulated, and the ratio between corn and soybean meal in these diets was
similar to that in the basal diet. Six additional diets that were similar to the
initial 6 diets with the exception that 1,000 units of microbial phytase were
added to the diets were also formulated. The ATTD and STTD of P were calculated
for each diet using the direct procedure, and the ATTD and STTD of P in each rice
coproduct were calculated using the difference procedure. Results of the
experiment indicated that the concentration of P in feces was reduced (P < 0.05)
from pigs fed diets with microbial phytase compared with pigs fed diets without
phytase. No differences were observed between the basal diet and the broken rice
diet, but the ATTD and the STTD of P in those diets was greater (P < 0.05) than
in all other diets both without and with phytase. Among the rice coproducts, the
greatest (P < 0.05) ATTD and STTD of P were observed for broken rice regardless
of inclusion of phytase. If no microbial phytase was used, the values for STTD of
P in brown rice, FFRB, DFRB, and rice mill feed were not different, but if
microbial phytase was included in the diet, ATTD and STTD of P in brown rice was
greater (P < 0.05) than in FFRB, DFRB, and rice mill feed. The STTD of P in brown
rice, FFRB, and rice mill feed was greater (P < 0.05) if microbial phytase was
used than if no microbial phytase was used. Addition of microbial phytase to the
diets also increased (P < 0.05) the ATTD of Ca regardless of the rice coproducts
used. In conclusion, the STTD of P is greater in broken rice than in all other
rice coproducts. The STTD of P in brown rice, FFRB, DFRB, and rice mill feed is
relatively low due to the high concentration of phytate in these ingredients, but
addition of microbial phytase will increase the STTD of P in most rice
coproducts.
PMID- 26440012
TI - Effects of environmental temperature and dietary manganese on egg production
performance, egg quality, and some plasma biochemical traits of broiler breeders.
AB - An experiment was conducted to investigate the effects of environmental
temperature and dietary Mn on egg production performance, egg quality, and some
plasma biochemical traits of broiler breeders. A completely randomized factorial
design involved 2 environmental temperatures (a normal temperature, 21 +/- 1
degrees C, and a high temperature, 32 +/- 1 degrees C) * 3 dietary Mn treatments
(a Mn-unsupplemented corn-soybean meal basal diet or the basal diet supplemented
with 120 mg of Mn/kg of diet as either MnSO4.H2O or manganese proteinate). There
were 6 treatments with 6 replicates (4 birds per replicate). High temperature
decreased egg weight (P < 0.0001), laying rate (P < 0.0001), egg yield (P <
0.0001), feed intake (P < 0.0001), egg:feed ratio (P < 0.0001), eggshell strength
(P < 0.05) and thickness (P < 0.0001), plasma triiodothyronine level (P < 0.05),
and alkaline phosphatase activity (P < 0.04) whereas it increased rectal
temperature (P < 0.0001); plasma malondialdehyde level (P < 0.02); and activities
(P < 0.002) of lactic dehydrogenase, aspartate aminotransferase, and creatine
kinase. Broiler breeders fed the diets supplemented with Mn regardless of source
had greater (P < 0.05) eggshell strength and lower (P <= 0.05) plasma
triiodothyronine level and protein carbonyl content than those fed the control
diet. The broiler breeders fed the diet supplemented with the organic Mn had
greater (P < 0.01) eggshell thickness than those fed the control diet. There were
interactions (P < 0.05) between environmental temperature and dietary Mn in
laying rate, egg yield, feed intake, and egg:feed ratio. Under normal
temperature, dietary Mn did not affect the above 4 parameters; however, under
high temperature, broiler breeders fed the diet supplemented with the organic Mn
showed greater (P < 0.03) improvements in these 4 parameters than those fed the
control diet. The results from this study indicated that high temperature
significantly impaired egg production performance and eggshell quality and
induced lipid peroxidation and tissue damage whereas dietary supplementation of
either organic or inorganic Mn improved eggshell strength and thermotolerance and
reduced protein oxidation and that the organic Mn could alleviate the negative
effect of high temperature on egg production performance of broiler breeders at
the period of 32 to 45 wk of age.
PMID- 26440014
TI - Effects of dietary supplementation with lysine-yielding Bacillus subtilis on gut
morphology, cecal microflora, and intestinal immune response of Linwu ducks.
AB - The effects of dietary supplementation with lysine-yielding Bacillus subtilis on
gut morphology, cecal microflora, and expression of intestinal cytokine mRNA of
Linwu ducks (a Chinese local domesticated duck) were investigated after a 63-d
feeding trial. Two hundred forty 1-d-old female ducklings were randomly assigned
to 1 of 4 dietary treatments, and there were 60 birds per treatment replicated 6
times with 10 birds each. The experimental diets consisted of a basal diet
containing no antibiotic or growth promoters, the basal diet supplemented with
150 mg Aureomycin per kg feed, and 2 others supplemented with 5.0 * 108 and 5.0 *
1010 cfu B. subtilis/kg feed, respectively. Birds fed the diets supplemented with
B. subtilis had increased (P < 0.001) villi height in the jejunum and ileum and
reduced (P < 0.001) crypt depth in the jejunum compared with birds fed the
control diet. Greatest (P < 0.01) villus height:crypt depth ratio was obtained
with the jejunum and ileum of birds fed the diet supplemented with 5.0 * 1010 cfu
B. subtilis/kg feed. Dietary supplementation with B. subtilis resulted in
increased (P < 0.05) cecal counts of Megasphaera elsdenii. Greater cecal
Lactobacillus counts were obtained in ducks fed the diets supplemented with
Aureomycin and B. subtilis. Ducks fed the diets supplemented with B. subtilis
showed suppressed (P < 0.001) expression of interleukin (IL)-1beta, IL-2, and IL
10 in their jejunum. When compared with the control, the expression of interferon
(IFN)-gamma in the jejunum of ducks fed the diet supplemented with 5.0 * 108 cfu
B. subtilis/kg feed was significantly increased (P < 0.05). Dietary
supplementation with B. subtilis or Aureomycin reduced (P < 0.001) ileal
expression of IL-10. When compared with the control, the expression of IL-2 and
IL-8 in the ileum of ducks fed the diet supplemented with 5.0 * 1010 cfu B.
subtilis/kg feed showed a significant decrease (P < 0.05). In conclusion, dietary
supplementation with lysine-yielding B. subtilis improved gut morphology,
increased the population of beneficial gut microflora, and stimulated increased
intestinal immune response of Linwu ducks.
PMID- 26440015
TI - Determination and prediction of energy values in corn distillers dried grains
with solubles sources with varying oil content for growing pigs.
AB - This study was conducted to determine the DE and ME content of 25 samples of corn
distillers dried grains with solubles (DDGS) fed to growing pigs and to generate
prediction equations for DE and ME based on chemical analysis. The 25 samples
included 15 full-oil (no oil extracted; ether extract [EE] > 8%) DDGS and 10
reduced-oil (oil extracted; EE < 8%) DDGS collected from 17 ethanol plants in
China. A corn-soybean meal diet constituted the basal diet and the other 25 diets
replaced a portion of the corn, soybean meal, and lysine of the basal diet with
28.8% of 1 of the 25 corn DDGS sources. Seventy-eight barrows (initial BW = 42.6
+/- 6.2 kg) were used in the experiment conducted over 2 consecutive periods (n =
6 per treatment) using a completely randomized design. For each period, pigs were
placed in metabolism cages for a 5-d total collection of feces and urine
following a 7-d adaptation to the diets. Among the 25 corn DDGS samples, EE, NDF,
DE, and ME content (DM basis) ranged from 2.8 to 14.2%, 31.0 to 46.6%, 3,255 to
4,103 kcal/kg, and 2,955 to 3,899 kcal/kg, respectively. Using a stepwise
regression analysis, a series of DE and ME prediction equations were developed
not only among all 25 DDGS but also only within 15 full-oil DDGS and 10 reduced
oil DDGS samples. The best fit equations of DE (kcal/kg DM) for the complete set
of 25 DDGS, 15 full-oil DDGS, and 10 reduced-oil DDGS were 2,064 - (38.51 * %
NDF) + (0.64 * % GE) - (39.70 * % ash), -(87.53 * % ADF) + (1.02 * % GE) - (22.99
* % hemicellulose), and 3,491 - (40.25 * % NDF) + (46.95 * % CP), respectively.
The best fit equations for ME (kcal/kg DM) for the complete set of 25 DDGS, 15
full-oil DDGS, and 10 reduced-oil DDGS were 1,554 - (44.11 * % NDF) + (0.77 * %
GE) - (68.51 * % ash), 7,898 - (42.08 * % NDF) - (136.17 * % ash) + (101.19 * %
EE) (103.83 * % CP), and 4,066 - (46.30 * % NDF) + (45.80 * % CP) - (106.19 * %
ash), respectively. Using the sum of squared residuals to compare the accuracy of
the 3 groups of prediction equations revealed that separate equations for full
oil DDGS and reduced-oil DDGS each provided a better fit than a single equation
for the entire set of DDGS sources. These results indicated that the DE and ME
values in corn DDGS are related to the chemical composition, primarily the EE and
fiber concentrations. Specific prediction equations derived from full-oil and
reduced-oil DDGS are better than equations derived from the entire set of DDGS.
PMID- 26440016
TI - Effects of protein intake on rate of growth, protein deposition, and carcass
traits of heavy Iberian pigs.
AB - A feeding, digestibility, and balance trial was performed to determine the effect
of the incorporation of increasing amounts of soybean protein concentrate (SPC)
to a basal acorn diet at a fixed energy intake on the rate of growth, protein
deposition (PD), and carcass traits of heavy Iberian (IB) pigs. Sixteen purebred
IB barrows (103.9 +/- 0.9 kg initial BW) were used. The pigs were individually
confined and allocated to 4 groups of 4 pigs each. Whole acorns were provided
with slight restriction to minimize acorn kernel (AK) remains. Water was freely
available. The incorporation of SPC raised the available CP from 49.1 g/kg DM
(1.91 g total Lys/kg DM) in AK up to 135 g/kg DM (7.24 g total Lys/kg DM). After
72 d of trial, the pigs achieved 134.4 +/- 1.3 kg BW and were then slaughtered.
Average daily BW gain increased with increasing dietary CP (linear, P < 0.001;
quadratic, P < 0.01), with a plateau at dietary CP concentrations (provided by AK
and SPC) beyond 72.2 and 100 g/kg DM, respectively, for which an ADG of 449 g was
achieved. There was a linear and quadratic effect of dietary CP and Lys level on
the apparent digestibility of CP (linear, P < 0.001; quadratic, P < 0.05) and on
the efficiencies of utilization of total N (retained N/N intake; linear, P <
0.001; quadratic, P < 0.001) and N apparently absorbed (retained N/apparent
digestible N; linear, P < 0.05; quadratic, P = 0.067). Protein deposition ranged
between -4.59 g/d in pigs not provided with SPC to 61.4 g/d in pigs fed the
greatest level of SPC inclusion. The lowest daily intake of total Lys resulting
in maximum PD (69.5 g/d) at the fixed level of energy intake observed (2.36 * ME
maintenance requirements) was 21.0 g. Hot carcass and cold carcass weights, but
not carcass yield, increased when feeding the daily ration containing 100 g SPC
and leveled off thereafter (linear, P < 0.01; quadratic, P < 0.01). An average
increase of 8.3% and 8.7% was obtained, respectively. The provision of SPC had no
effect on back fat thickness. Primal cuts, but not yield (except for loin),
increased (sirloin: linear, P < 0.05; loin: linear, P < 0.001; quadratic, P <
0.05; ham: linear, P < 0.05) or showed a tendency to increase (butt lean: linear,
P = 0.068; quadratic, P = 0.077; ribs: quadratic, P = 0.067; shoulder: quadratic,
P = 0.064) with the provision of dietary protein. No effect of the level of
incorporation of SPC to the diet was observed on CP, total fat, total ash, and
energy contents or on relative fatty acid profile of loin and sirloin.
PMID- 26440017
TI - Effect of supplementing a fibrous diet with a xylanase and beta-glucanase blend
on growth performance, intestinal glucose uptake, and transport-associated gene
expression in growing pigs.
AB - The present study evaluated supplemental carbohydrase effect on performance,
intestinal nutrient uptake, and transporter mRNA expressions in growing pigs
offered a high-fiber diet manufactured with distillers dried grains with solubles
(DDGS). Twenty-four pigs (22.4 +/- 0.7 kg BW) were randomly assigned to 1of 3
nutritionally adequate diets (8 pigs per diet) based on corn and soybean meal
(SBM) with either 0 (control) or 30% DDGS (high fiber [HF]). The third diet was
supplemented with a xylanase and beta-glucanase blend (XB) in addition to the 30%
DDGS (HF+XB). Parameters determined were ADFI, ADG, G:F, plasma glucose and
plasma urea nitrogen (PUN) concentrations, jejunal tissue electrophysiological
properties, and mRNA expressions of the sodium-dependent glucose transport 1
(SGLT1) and cationic AA transporter, bo,+AT, in the jejunal and ileal tissues. In
addition, mRNA expressions of the short-chain fatty acid transporters,
monocarboxylate transporter 1 (MCT1) and sodium-coupled monocarboxylate
transporter, and mucin genes were quantified in the ileum. Feed intake, plasma
glucose, and jejunal tissue electrophysiological properties were not affected (P
> 0.05) by diet. However, control-fed pigs had superior growth rate and feed
efficiency and higher PUN (P < 0.05) than HF- and HF+XB-fed pigs. The HF diet
increased (P < 0.05) SGLT1 mRNA expression in the jejunum and decreased (P <
0.05) bo,+ mRNA expression in the ileum. The XB supplementation also increased
bo,+ mRNA expression in the ileum relative to HF-fed pigs. Additionally, MCT1
mRNA expression was greater (P < 0.05) in the ileum of the HF- and HF+XB-fed
pigs. In the present study, XB supplementation influenced nutrient transporter
mRNA expression, although it was not accompanied by improved pig performance.
PMID- 26440018
TI - Apparent and standardized total tract digestibility by growing pigs of phosphorus
in canola meal from North America and 00-rapeseed meal and 00-rapeseed expellers
from Europe without and with microbial phytase.
AB - An experiment was conducted to determine apparent total tract digestibility
(ATTD) and standardized total tract digestibility (STTD) by growing pigs of P in
canola meal, 00-rapeseed meal, and 00-rapeseed expellers. Canola meal and 00
rapeseed meal are the coproducts produced after the residual oil has been solvent
extracted from the prepressed canola seeds and 00-rapeseeds, respectively,
whereas 00-rapeseeed expellers is the coproduct from 00-rapeseeds that have been
only expeller pressed. Two hundred sixteen barrows (18.0 +/- 1.5 kg initial BW)
were allotted to 36 diets and 6 replicate pigs per diet. Five samples of canola
meal from solvent-extraction crushing plants in North America, 8 samples of 00
rapeseed meal from solvent-extraction crushing plants in Europe, and 5 samples of
00-rapeseed expellers from mechanical-press crushing plants in Europe were used
in the experiment. Eighteen diets were prepared by including 40% of each source
of canola meal, 00-rapeseed meal, or 00-rapeseed expellers in 1 diet. Eighteen
additional diets were formulated by adding 1,500 units of microbial phytase to
the diets. The only source of P in the diets was canola meal, 00-rapeseed meal,
or 00-rapeseed expellers. Pigs were placed in metabolism crates that allowed for
total fecal collection. Pigs were fed at 2.5 times their estimated energy
requirement for maintenance. Ingredients, diets, and feces were analyzed for P,
and the ATTD and STTD of each source of canola meal, 00-rapeseed meal, and 00
rapeseed expellers were calculated. A value for endogenous P loss of 190 mg/kg
DMI was used to calculate the STTD of P. Results indicated that the ATTD and STTD
of P for canola meal were not different from values obtained in 00-rapeseed meal,
and the ATTD and STTD of P in 00-rapeseed meal were not different from values for
00-rapeseed expellers. The ATTD and STTD of P increased (P < 0.001) from 44.99
and 48.82% to 64.08 and 67.97% for canola meal, from 46.77 and 50.36% to 63.53
and 67.29% for 00-rapeseed meal, and from 44.83 and 48.60% to 69.18 and 72.99%,
respectively, for 00-rapeseed expellers by adding microbial phytase to the diets.
In conclusion, although the concentration of ether extract is much greater in 00
rapeseed expellers than in 00-rapeseed meal and canola meal, the ATTD and STTD of
P for these ingredients are not different, and addition of microbial phytase
results in improved digestibility of P in canola meal, 00-rapeseed meal, and 00
rapeseed expellers.
PMID- 26440019
TI - Developmental changes in polyamines and autophagic marker levels in normal and
growth-restricted fetal pigs.
AB - Polyamines are essential for embryonic and fetal survival, growth, and
development. Additionally, polyamines may induce autophagy in mammalian cells.
However, little is known about the availability of polyamines or autophagy in the
porcine conceptus with intrauterine growth restriction (IUGR). The present study
was performed to evaluate the developmental changes of polyamine concentrations
in IUGR and normal porcine fetuses as well as autophagic marker levels in the
fetal intestinal mucosa during the second half of gestation when most fetal
growth occurs. Allantoic fluid (ALF), amniotic fluid (AMF), umbilical vein, and
the small-intestinal mucosa were obtained from both IUGR and normal fetal pigs at
d 60, 90, and 110 of gestation. Concentrations of polyamines in fetal fluids as
well as protein abundances of microtubule-associated protein light chain 3B
(LC3B), an autophagic marker, in the fetal small-intestinal mucosa were
determined. Concentrations of polyamines varied greatly in different fetal
compartments and changed substantially with advancing gestation. Concentrations
of polyamines in IUGR fetal fluids and the small-intestinal mucosa were markedly
different from those in their normal counterparts at d 60 and 90 of gestation,
whereas most of the differences were not detected by late (d 110) gestation.
Specifically, polyamine levels were lower in the umbilical vein plasma but higher
in ALF and AMF from IUGR fetuses. Furthermore, enhanced levels of an autophagic
marker were observed in the small-intestinal mucosa of IUGR fetuses throughout
mid and late gestation in association with abnormal spermidine levels in fetal
plasma. These findings support the notion that enhanced autophagy may be an
important survival mechanism in IUGR fetuses. Collectively, our findings provide
a new framework for future studies to define the roles for polyamines in the
prevention and treatment of IUGR in both human medicine and animal production.
PMID- 26440020
TI - In vitro and in vivo digestibility of corn starch for weaned pigs: Effects of
amylose:amylopectin ratio, extrusion, storage duration, and enzyme
supplementation.
AB - The objective of this study was to investigate the effects of amylose
(AM):amylopectin (AP) ratio, extrusion, storage duration, and enzyme
supplementation on starch digestibility of corn. Three corn varieties with high
(0.60; HA), medium (0.44; MA), and low (0.39; LA) AM:AP ratios, respectively,
were selected from 74 corn samples to evaluate the in vitro and in vivo
digestibility of starch. In Exp. 1, during wk 4 after extrusion, resistant starch
(RS) content of the 3 selected corn varieties (LA, MA, and HA) increased (P <
0.05) each week and starch digestibility in vitro decreased as storage time
increased (P < 0.05). The AM:AP ratio affected the formation of RS (P < 0.01).
The RS content of the 3 corn varieties was ranked as LA < MA < HA in each week (P
< 0.05). Correlation analysis showed that AM:AP ratio and storage duration were
both positively correlated with RS content (P < 0.01). Furthermore, a significant
quadratic relation was found between storage duration and RS content in each corn
variety as well as storage duration and digestibility. Starch digestibility was
negatively correlated with RS content (P < 0.001). In Exp. 2, digestion trials
were performed on cannulated pigs with BW of 13.20 +/- 0.94 kg. Extrusion
increased ileal digestibility of GE and starch of either HA or LA compared with
the enzyme-supplemented diets (P < 0.001). Enzyme supplementation did not improve
ileal energy and starch digestibility. The ileal digestibility of starch and GE
of LA varieties was greater than HA samples (P < 0.05). The results implied that
AM:AP ratio and storage duration after extrusion may be important determinants of
RS formation and digestibility of starch for corn. In addition, RS content could
be an important indicator of digestibility of starch in extruded corn. Using a
lower AM:AP ratio corn or reducing the storage duration of extruded corn would
help to reduce the formation of RS and improve the starch bioavailability of corn
for piglets.
PMID- 26440021
TI - Age at puberty, ovulation rate, and uterine length of developing gilts fed two
lysine and three metabolizable energy concentrations from 100 to 260 d of age.
AB - The objective of this study was to determine the effect of ad libitum feeding
diets differing in standard ileal digestible (SID) lysine and ME concentrations
that bracket those fed to developing gilts in U.S. commercial settings. Average
SID lysine and ME concentrations in diets currently fed to developing gilts were
obtained from a poll of the U.S. commercial swine industry. Crossbred Large White
* Landrace gilts (n = 1,221), housed in groups, were randomly allotted to 6 corn
soybean diets in a 2 * 3 factorial arrangement formulated to provided 2 SID
lysine and 3 ME concentrations. Gilts received grower diets formulated to provide
1.02% (control = survey average) or 0.86% (control minus 15%) SID lysine and
2.94, 3.25, or 3.57 (survey average ME +/- 10%) Mcal of ME/kg from 100 d of age
until approximately 90 kg BW. Then, gilts were fed finisher diet containing 0.85%
(control = survey average) or 0.73% (control minus 15%) SID lysine and 2.94,
3.26, or 3.59 (control +/- 10%) Mcal of ME/kg until 260 d of age. Gilts were
weighed, and backfat thickness and loin muscle area were recorded at the
beginning of the trial and then every 28 d. Starting at 160 d of age, gilts were
exposed daily to vasectomized boars and observed for behavioral estrus. At
approximately 260 d of age, gilts were slaughtered and their reproductive tract
was collected. Each reproductive tract was examined to determine whether the gilt
was cyclic, the stage of estrus cycle, ovulation rate, and uterine length. Data
were evaluated for normality and analyzed using mixed model methods. Average age
at puberty was 193 d of age with a range from 160 to 265 d. When all gilts on
trial at 160 d of age were included in the analysis, 91.0% reached puberty as
determine by observation of standing estrus. Differences between dietary
treatments on age at puberty or measurements of the reproductive tract were not
detected. Growth rates to 160 d were not limiting for attainment of puberty in
response to daily boar stimulation from 160 d.
PMID- 26440022
TI - Postnatal bacterial succession and functional establishment of hindgut in
supplemental feeding and grazing goats.
AB - The objectives of this study were 1) to investigate the age-related changes in
functional achievement (establishment of fermentation capacity and enzyme
activities) and bacterial succession (selected functional bacterial species) in
the cecum and colon and 2) to assess the effect of feeding system (supplemental
vs. grazing, Sup vs. G) on hindgut development in small ruminants. A total of 44
Liuyang black goat kids were randomly slaughtered at 0, 7, and 14 d of age
(nonrumination period), 28 and 42 d of age (transition period), and 56 and 70 d
of age (rumination period). Intestinal contents were sampled to determine VFA,
activities of amylase, carboxymethylcellulase (CMCase), and xylanase, as well as
abundances of total bacteria and selected functional bacterial species (genus
Prevotella, cellulolytic and amylolytic bacteria) with quantitative PCR targeting
the 16S rRNA subunit genes. Total VFA concentration (P < 0.01) and enzyme
activities (P < 0.05) in hindgut contents were greater and total bacterial 16S
rRNA gene copy numbers (P = 0.003) in the cecum were lower for Sup vs. G.
Furthermore, irrespective of feeding system, hindgut total VFA concentrations and
total bacterial 16S rRNA gene copy numbers increased with age (P < 0.01), with
the greatest increase rate observed from 14 to 28 d. Amylase fluctuated with age,
whereas CMCase and xylanase activities in Sup kids increased (P < 0.05) as age
increased. The proportions of 16S rRNA copy numbers associated with the genus
Prevotella and P. ruminicola increased (P < 0.05) with age, but those of
cellulolytic bacteria and Ruminobacter amylophilus were detected only after 28 d
of birth. The bacterial succession, fermentation capacity, and starch-degrading
capacity in the hindgut of both groups were achieved at 1 mo, whereas fiber
degrading capacity in Sup kids was established at 2 mo of age; and supplemental
feeding surpassed the grazing system in shaping hindgut development.
PMID- 26440023
TI - Effects of chitosan on nutrient digestibility, methane emissions, and in vitro
fermentation in beef cattle.
AB - Chitosan was evaluated as a feed additive to mitigate in vivo CH4 emissions in
beef cattle. Twenty-four crossbred heifers (BW = 318 +/- 35 kg) were used in a
randomized block design replicated in 2 periods. The design included a 2 * 3
factorial arrangement of treatments, which included diet (high concentrate [HC]
or low concentrate [LC]) and 0.0, 0.5, or 1.0% of chitosan inclusion (DM basis).
Diets were offered ad libitum and individual intake was recorded. An in vitro
experiment to analyze chitosan's effect on fermentation parameters and gas
production kinetics was performed. A diet effect (P < 0.01) was observed for CH4
emissions expressed as grams/day, grams/kilogram of BW0.75, and grams/kilogram of
DMI. Heifers consuming the LC diet produced 130 g of CH4/d vs. 45 g of CH4/d in
those consuming the HC diet. Incubation fluid pH increased linearly (P < 0.05)
when chitosan was included in HC substrates. In vitro CH4 production was not
affected (P > 0.10) by chitosan in HC substrate; however, when incubated with the
LC substrate, CH4 production increased quadratically (P < 0.01) as chitosan
inclusion increased. A digestibility marker * diet interaction occurred (P <
0.05) for DM, OM, CP, NDF, and ADF digestibility. Diet * chitosan interactions (P
< 0.05) occurred for DM, OM, NDF, and ADF digestibility when Cr2O3 was used. When
TiO2 was used, diet * chitosan interactions (P < 0.05) were observed for NDF and
ADF. However, using indigestible NDF as an internal marker, DM and OM
digestibility were improved (P < 0.05) by 21 and 19%, respectively, when chitosan
was included in LC diets. In conclusion, feeding up to 1% of chitosan (DM basis)
to heifers consuming a LC diet increased apparent total tract digestibility of
nutrients. Enteric CH4 emissions were not affected by chitosan feeding,
regardless of type of diet, and heifers consuming a 36% concentrate diet produced
2.6 times more methane per day than those consuming an 85% concentrate diet.
PMID- 26440024
TI - A modified version of the Molly rumen model to quantify methane emissions from
sheep.
AB - We modified the rumen submodel of the Molly dairy cow model to simulate the rumen
of a sheep and predict its methane emissions. We introduced a rumen hydrogen (H2)
pool as a dynamic variable, which (together with the microbial pool in Molly) was
used to predict methane production, to facilitate future consideration of
thermodynamic control of methanogenesis. The new model corrected a
misspecification of the equation of microbial H2 utilization in Molly95, which
could potentially give rise to unrealistic predictions under conditions of low
intake rates. The new model included a function to correct biases in the
estimation of net H2 production based on the default stoichiometric relationships
in Molly95, with this function specified in terms of level of intake. Model
parameters for H2 and methane production were fitted to experimental data that
included fresh temperate forages offered to sheep at a wide range of intake
levels and then tested against independent data. The new model provided
reasonable estimates relative to the calibration data set, but a different
parameterization was needed to improve its predicted ability relative to the
validation data set. Our results indicate that, although feedback inhibition on
H2 production and methanogen activity increased with feeding level, other
feedback effects that vary with diet composition need to be considered in future
work on modeling rumen digestion in Molly.
PMID- 26440025
TI - Additive methane-mitigating effect between linseed oil and nitrate fed to cattle.
AB - The objective of this study was to test the effect of linseed oil and nitrate fed
alone or in combination on methane (CH4) emissions and diet digestibility in
cows. The experiment was conducted as a 2 * 2 factorial design using 4
multiparous nonlactating Holstein cows (initial BW 656 +/- 31 kg). Each
experimental period lasted 5 wk, with measures performed in the final 3 wk (wk 3
to 5). Diets given on a DM basis were 1) control (CON; 50% natural grassland hay
and 50% concentrate), 2) CON with 4% linseed oil (LIN), 3) CON with 3% calcium
nitrate (NIT), and 4) CON with 4% linseed oil plus 3% calcium nitrate (LIN+NIT).
Diets were offered twice daily and were formulated to deliver similar amounts (DM
basis) of CP (12.2%), starch (25.5%), and NDF (39.5%). Feed offer was restricted
to 90% of voluntary intake (12.4 kg DMI/d). Total tract digestibility and N
balance were determined from total feces and urine collected separately for 6 d
during wk 4. Daily CH4 emissions were quantified using open chambers for 4 d
during wk 5. Rumen fermentation and microbial parameters were analyzed from
samples taken before and 3 h after the morning feeding. Rumen concentrations of
dissolved hydrogen (H2) were measured continuously up to 6 h after feeding using
a H2 sensor. Compared with the CON diet linseed oil and nitrate decreased (P <
0.01) CH4 emissions (g/kg DMI) by 17 and 22%, respectively, when fed alone and by
32% when combined. The LIN diet reduced CH4 production throughout the day,
increased (P = 0.02) propionate proportion, and decreased (P = 0.03) ruminal
protozoa concentration compared with CON diet. The NIT diet strongly reduced CH4
production 3 h after feeding, with a simultaneous increase in rumen dissolved H2
concentration, suggesting that nitrate does not act only as an electron acceptor.
As a combined effect, linseed plus nitrate also increased H2 concentrations in
the rumen. Diets had no effect (P > 0.05) on total tract digestibility of
nutrients, except linseed oil, which tended to reduce (P < 0.10) fiber
digestibility. Nitrogen balance (% of N intake) was positive for all diets but
retention was less (P = 0.03) with linseed oil. This study demonstrates an
additive effect between nitrate and linseed oil for reducing methanogenesis in
cows without altering diet digestibility.
PMID- 26440026
TI - Feed restriction and subsequent realimentation in Holstein Friesian bulls: I.
Effect on animal performance; muscle, fat, and linear body measurements; and
slaughter characteristics.
AB - Holstein Friesian bulls (n = 75) were used to evaluate the effect of restricted
and subsequent compensatory growth on muscular and skeletal growth as well as the
recovery of carcass and noncarcass components. Fifteen bulls were slaughtered on
Day 0 to provide baseline parameters for carcass and noncarcass measurements. Of
the remaining 60 bulls, 30 were fed ad libitum (ADLIB) and 30 were fed a
restricted (RES) diet to grow at 0.6 kg/d for 125 d, denoted as Period 1. After
125 d of differential feeding, 15 bulls from each group were slaughtered. The
remaining bulls in both treatment groups were then offered ad libitum access to
feed for a further 55 d (realimentation), denoted as Period 2, after which they
were also slaughtered. All animals received the same diet composed of 70%
concentrate and 30% grass silage throughout the experimental trial. As planned,
feed intake was greater for ADLIB bulls in Period 1 (P < 0.001); however, there
was no difference in feed intake during realimentation (P > 0.05). During Period
1, RES bulls gained 0.6 kg/d whereas ADLIB bulls grew at 1.9 kg/d. During
realimentation in Period 2, RES bulls displayed accelerated growth, gaining 2.5
kg/d compared with 1.4 kg/d for ADLIB bulls (P < 0.001). This amounted to a live
weight difference between treatment groups of 161 kg at the end of Period 1 after
restricted feeding, which was then reduced to 84 kg at the end of Period 2 (P <
0.001). Restricted animals achieved a compensatory growth (or recovery) index of
48% within 55 d of realimentation. During Period 2, RES bulls displayed a better
feed conversion ratio (P < 0.001) than ADLIB bulls, indicating better feed
efficiency. Ultrasonically measured longissmus dorsi growth was greater for ADLIB
bulls compared with RES bulls during Period 1; however, this was reversed during
Period 2 (P < 0.001). Metabolically active organs such as the liver and
components of the gastrointestinal tract were lighter in RES bulls at the end of
Period 1, with no difference in the weights of these components after
realimentation (P < 0.01). The improved feed efficiency and muscle growth
observed during feed restriction induced compensatory growth may be as a
consequence of latent effects of reduced requirements of energetically demanding
tissues into realimentation.
PMID- 26440027
TI - Feed restriction and realimentation in Holstein-Friesian bulls: II. Effect on
blood pressure and systemic concentrations of metabolites and metabolic hormones.
AB - The objective of this study was to evaluate the endocrine response and metabolic
rate in Holstein-Friesian bulls during restricted feeding and realimentation.
Sixty bulls were allocated to 1 of 2 feeding regimes: 1) restricted feed
allowance (RES; n = 30) or 2) ad libitum feeding (ADLIB; n = 30) for 125 d
(Period 1). The bulls in both treatment groups were then offered ad libitum
access to feed for a further 55 d (Period 2). Five and 4 blood samples were
collected during periods 1 (n = 60) and 2 (n = 30), respectively. Plasma samples
were assayed for hormones and metabolites including insulin, IGF-1, leptin,
thyroid hormones, albumin, beta-hydroxy butyrate (BHB), creatinine, glucose,
NEFA, total protein, triglycerides, and urea. Blood pressure measurements were
determined on all animals at the beginning and end of each period as an indicator
of metabolic rate. During Period 1, RES bulls gained 0.6 kg/d whereas ADLIB bulls
grew at 1.9 kg/d. Following realimentation in Period 2, RES bulls displayed
accelerated growth, gaining 2.5 kg/d compared with 1.4 kg/d for ADLIB bulls (P <
0.001). Treatment * period interactions (P < 0.05) were evident for all plasma
analytes assayed. During Period 1, RES bulls had lower concentrations of glucose
and insulin, reflecting their lower feed intake. Adipose and protein tissue
mobilization was evident through greater concentrations of triglycerides, NEFA,
BHB, creatinine, albumin, and total protein in RES animals in Period 1.
Additionally, the effect of restricted feeding on growth was apparent through
lower concentrations of IGF-1. A lower metabolic rate was also apparent through
lower concentrations of thyroid hormones and fewer beats per minute in RES bulls
during Period 1. During the initial stage of realimentation in Period 2, IGF-1,
insulin, thyroid hormones, creatinine, glucose, total protein, and triglycerides
followed the same pattern as per Period 1 with divergence maintained between RES
and ADLIB bulls (P < 0.05), whereas concentrations of all of these hormones and
metabolites had converged between the treatment groups by the end of Period 2.
During realimentation, the number of heart beats per minute was greater in RES
bulls, indicating greater metabolic rate in these animals (P < 0.001). Results
from the current study clearly show that feed restriction followed by
realimentation affects key indices of metabolic status as well as tissue
catabolism and provides an insight into the metabolic control of compensatory
growth in cattle.
PMID- 26440028
TI - Effects of residual feed intake and dam body weight on replacement heifer intake,
efficiency, performance, and metabolic response.
AB - Thirty-eight Angus-based, crossbred, nulliparous beef heifers (BW = 280 +/- 26.3
kg) sired by 2 Angus sires were used to determine if dam BW affected heifer
performance, DMI, residual feed intake (RFI), and endocrine markers. Heifers were
housed in individual pens (2.2 by 9.1 m) equipped with 2.2 m of bunk space and
fed a diet (90.4% DM, 13.7% CP, 67.2% NDF, and 56.2% TDN) consisting of 87.2%
bermudagrass hay and 12.8% liquid protein supplement for a 14-d adaption period
and a 70-d feeding period. Individual daily feed intake was used to calculate RFI
for each heifer, and heifer was the experimental unit. Two-day beginning and end
BW were recorded and hip height was used to calculate frame score (FS). Heifer
dams were assigned to a light (LIT; 544 +/- 21.3 kg) or heavy (HEV; 621 +/- 34.8
kg) BW group on the basis of mean BW at the beginning of their lactation period
the previous year to determine differences in heifer offspring DMI and RFI. Based
on heifer RFI ranking, heifers were classified as positive (POS; 0.34) or
negative (NEG; -0.31) RFI and low (LOW; -0.45), medium (MED; 0.00), or high (HI;
0.49) RFI for analysis of BW, FS, BW gain, and DMI. There were no dam BW group *
sire interactions (P > 0.10) for all independent variables. Beginning and end BW
was greater (P < 0.05) for heifers out of HEV compared with LIT BW dams. Body
weight gain, ADG, FS, DMI, and RFI were not significant (P > 0.10) for heifers
out of HEV compared with LIT BW dams; however, a sire effect existed (P < 0.01)
for BW gain, ADG, FS, and DMI. Among RFI classifications, beginning and end BW,
BW gain, ADG, and FS were not different (P > 0.10) whereas DMI was greater (P =
0.03) among heifers in the POS compared with the NEG RFI group and greater (P =
0.01) among heifers in the MED and HI compared with LOW RFI group, respectively.
Plasma insulin levels were greater (P = 0.03) in the NEG compared with the POS
RFI heifers, and thyroxine (T4) levels were greater (P = 0.02) in the POS
compared with the NEG RFI heifers. A positive relationship existed (P <= 0.05)
between dam BW and heifer DMI (r = 0.42), beginning and end BW (r = 0.45 and 54),
and FS (r = 0.58) and between RFI and d 70 triiodothyronine (r = 0.34), d 70 T4
(r = 0.35), and d 0 and 70 combined T4 (r = 0.32), respectively. Heifers out of
dams from the HEV BW group were heavier and a positive correlation existed
between dam BW and heifer BW, gain, DMI, and FS, which can impact selection goals
for replacement heifers.
PMID- 26440029
TI - Effects of grind size when alkaline treating corn residue and impact of ratio of
alkaline-treated residue and distillers grains on performance of finishing
cattle.
AB - Two studies were conducted to optimize use of alkaline-treated corn stover and
wheat straw and distillers grains as partial corn replacements. In Exp. 1, a
finishing experiment used 30 pens (12 steers/pen) of calf-fed steers (initial BW
= 374 +/- 23.9 kg) with a 2 * 2 + 1 factorial arrangement of treatments with 6
replications per treatment. Factors were grind size, where corn stover was
processed through a 2.54- or 7.62-cm screen, and chemical treatment (corn stover
either fed in native, non-treated form [NT; 93.4% DM] or alkaline treated [AT; 5%
CaO hydrated to 50% DM]). No interactions (P >= 0.38) were noted between grind
size and chemical treatment. Feeding AT compared with NT improved (P <= 0.02)
final BW, ADG, and G:F. Reducing grind size improved (P <= 0.01) ADG and G:F, and
no interaction with chemical treatment was observed. Steers fed AT had similar
DMI, ADG, G:F, and carcass characteristics compared with a 5% roughage control
that contained 15 percentage units (DM basis) more corn. In Exp. 2, 60
individually fed steers (initial BW = 402 +/- 61.4 kg) were randomly assigned to
10 diets. Six treatments evaluated 10, 25, or 40% dry-rolled corn (DRC), which
was replaced with either a 2:1 or 3:1 ratio (DM basis) of modified distillers
grains plus solubles (MDGS) and treated corn stover analyzed as a 2 * 3
factorial. An additional 3 treatments were added where a 3:1 ratio of MDGS:straw
were compared with a 3:1 ratio of MDGS:stover. As DRC increased, G:F (P = 0.06)
quadratically increased for 3:1 MDGS:stover diets. Increasing DRC increased (P =
0.07) G:F in treated stover diets, regardless of ratio. Increasing DRC increased
(P = 0.10) ADG for 3:1 ratios for both straw and stover. Reducing grind size,
feeding a maximum of 20% treated crop residue, and maintaining at least 25% corn
in the diet are strategies for optimizing cattle performance when replacing dry
rolled and high-moisture corn with treated crop residues and distillers grains.
PMID- 26440030
TI - Trailer temperature and humidity during winter transport of cattle in Canada and
evaluation of indicators used to assess the welfare of cull beef cows before and
after transport.
AB - The current study evaluated 17 loads of cull beef cows transported in Canadian
winter conditions to assess in-transit temperature and humidity, evaluation of
events during loading and unloading, and animal condition and bruising.
Regardless of the use of boards to block ventilation holes in trailers,
temperatures were higher within trailers than at ambient locations during both
travel and stationary periods (P < 0.01). Boarding was associated with smaller
differences in trailer temperature, compared with ambient conditions, while the
trailer was traveling at highway speeds versus when trailers were stationary (P <
0.01). Moisture levels within trailers were not different from ambient conditions
when loads using boarding were traveling (P < 0.01), whereas loads without
boarding had a larger difference (P < 0.01). The moisture within trailers
relative to ambient conditions increased when trailers were stationary compared
with traveling when boarding was used (P < 0.01). The majority of cattle
transported were in good body condition (97.4% within BCS of 2 to 3.5) and had
calm temperaments (96.7%). Although all comparisons were made, only the doghouse
compartment had an increased risk of severe bruising compared with all other
compartments (odds ratio [95% confidence interval]: 3.0 [1.6-5.5], 3.7 [2.1-6.4],
2.2 [1.3-3.7] and 3.8 [1.5-9.6] in comparison with the back, belly, deck, and
nose compartments, respectively; P < 0.05). Increasing the duration of waiting to
unload 30 min relative to a 1 h duration increased the odds of severe bruising by
1.18 times (95% confidence interval: 1.09-1.29; P < 0.01). Scoring systems that
have been developed for auditing unloading of cattle had limited variation across
loads at both loading and unloading. Pretransport assessment of animal condition
using the American Meat Institute's compromised animal score was the only scoring
system that was consistent with posttransport scores. We inferred from the
temperature and humidity data in the current study that under commercial
conditions, boarding may increase ventilation within trailers during travel and
decrease ventilation during stationary periods. The current study provides the
first indication that issues in Canadian cull cow transport may be related to
pretransport animal condition and management of unloading.
PMID- 26440031
TI - Technical note: Digital quantification of eye pigmentation of cattle with white
faces.
AB - Cancer of the eye in cattle with white faces occurs less frequently in cattle
with pigmented eyelids. Corneoscleral pigmentation is related to eyelid
pigmentation and occurrence of lesions that may precede cancer. Objectives of
this study were to assess 1) variation in the proportion of eyelid and
corneoscleral pigmentation in Hereford, Bos taurus, and Bos indicus crossbreds
and 2) the occurrence of lesions with the presence of pigmentation in those
areas. Hereford and Bos indicus crosses (Brahman or Nellore with Angus and
Hereford and straightbred Brafords) and Bos taurus crosses (Angus-Hereford) were
included in the study (n = 1,083). Eyelid pigmentation proportions were estimated
by pixel quantification and were evaluated as total proportions and for upper and
lower eyelids distinctly for each eye. Fixed effects included breed type, age
categories, and sex of the animal. Lesion presence (1) or absence (0) was
obtained by visual appraisal of image and was assumed to be binomially
distributed. Eyelid pigmentation proportions (overall, upper, and lower eyelids)
for Hereford ranged from 0.65 +/- 0.03 to 0.68 +/- 0.03 and were significantly
lower than Bos indicus (range from 0.93 +/- 0.02 to 0.95 +/- 0.02) or Bos taurus
(ranged from 0.88 +/- 0.02 to 0.92 +/- 0.02) crosses. Corneoscleral pigmentation
in Hereford cows (0.17 +/- 0.06) did not differ (P = 0.91) from Hereford calves
and yearlings (0.16 +/- 0.07). Bos indicus and Bos taurus crossbred cows had
larger corneoscleral pigmentation (0.38 +/- 0.05 and 0.48 +/- 0.04 for left eyes
and 0.37 +/- 0.05 and 0.53 +/- 0.04 for right eyes, respectively) than all calves
(P < 0.001), and their corneoscleral pigmentations were greater than that of
Hereford cows (P < 0.003). Bos indicus and Bos taurus cows had greater
proportions of left eye corneoscleral pigmentation (0.38 +/- 0.05 and 0.48 +/-
0.04, respectively) than Hereford cows (0.17 +/- 0.06) and all young animal breed
types (P < 0.05). Right eye proportions differed for all cow groups (P < 0.05;
0.53 +/- 0.04, 0.37 +/- 0.05, and 0.17 +/- 0.06). Among calves and yearlings,
Hereford had a lower right eye corneoscleral pigmentation proportion (0.16 +/-
0.07) than Bos taurus (P = 0.02). The lesion proportion for Hereford (0.08 +/-
0.03) was significantly greater than that of either Bos indicus (0.01 +/- 0.005)
or Bos taurus (0.01 +/- 0.003). Crossbreeding with Bos taurus or Bos indicus
animals appears to increase eye pigmentation, which may help reduce the
occurrence of cancer in eyes of cattle with white faces.
PMID- 26440032
TI - Evaluation of multiple ancillary therapies used in combination with an
antimicrobial in newly received high-risk calves treated for bovine respiratory
disease.
AB - Ancillary therapy (ANC) is commonly provided in conjunction with an antimicrobial
when treating calves for suspected bovine respiratory disease (BRD) in an attempt
to improve the response to a suspected BRD challenge. The first experiment
evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk
calves treated for BRD during a 56-d receiving period. Newly received crossbred
steers (n = 516; initial BW = 217 +/- 20 kg) were monitored by trained personnel
for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n =
320) were then randomly assigned to experimental ANC treatment (80
steers/experimental ANC treatment): intravenous flunixin meglumine injection
(NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection
(VITC), or no ANC (NOAC). Animal served as the experimental unit for all
variables except DMI and G:F (pen served as the experimental unit for DMI and
G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P <
0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis
of observed clinical signs and severity) and heavier (P = 0.01) BW than those
receiving NSAID, VACC, or VITC at the time of third treatment. Between the second
and third BRD treatments, calves receiving NOAC had decreased (P < 0.01) daily BW
loss (-0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (-1.30,
1.90, and -1.41 kg ADG, respectively). There were no differences in rectal
temperature, combined mortalities and removals, or overall performance among the
experimental ANC treatments. Overall, morbidity and mortality attributed to BRD
across treatments were 66.5% and 13.2%, respectively. After the receiving period,
a subset of calves (n = 126) were allocated to finishing pens to evaluate the
effects ANC administration on finishing performance, carcass characteristics, and
lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used
to target a common physiological end point for each pen of calves. There were no
differences among the experimental ANC observed during the finishing period (P >=
0.11). In summary, the use of NSAID, VACC, and VITC do not appear to positively
impact clinical health and could potentially be detrimental to performance during
the receiving period in high-risk calves receiving antimicrobial treatment for
suspected BRD.
PMID- 26440033
TI - Evaluation of the effect of alternative measurements of body weight gain and dry
matter intake for the calculation of residual feed intake in growing purebred
Charolais and Red Angus cattle.
AB - The objective of this study was to determine the effects of alternative
measurements of body weight and DMI used to evaluate residual feed intake (RFI).
Weaning weight (WW), ADG, and DMI were recorded on 970 growing purebred Charolais
bulls (n = 519) and heifers (n = 451) and 153 Red Angus growing steers (n = 69)
and heifers (n = 84) using a GrowSafe (GrowSafe, Airdrie, Alberta, Canada)
system. Averages of individual DMI were calculated in 10-d increments and
compared to the overall DMI to identify the magnitude of the errors associated
with measuring DMI. These incremental measurements were also used in calculation
of RFI, computed from the linear regression of DMI on ADG and midtest body
weight0.75 (MMWT). RFI_Regress was calculated using ADG_Regress (ADG calculated
as the response of BW gain and DOF) and MMWT_PWG (metabolic midweight calculated
throughout the postweaning gain test), considered the control in Red Angus. A
similar calculation served as control for Charolais; RFI was calculated using 2-d
consecutive start and finish weights (RFI_Calc). The RFI weaning weight (RFI_WW)
was calculated using ADG_WW (ADG from weaning till the final out weight of the
postweaning gain test) and MMWT_WW, calculated similarly. Overall average
estimated DMI was highly correlated to the measurements derived over shorter
periods, with 10 d being the least correlated and 60 d being the most correlated.
The ADG_Calc (calculated using 2-d consecutive start and finish weight/DOF) and
ADG_WW were highly correlated in Charolais. The ADG_Regress and ADG_Calc were
highly correlated, and ADG_Regress and ADG_WW were moderately correlated in Red
Angus. The control measures of RFI were highly correlated with the RFI_WW in
Charolais and Red Angus. The outcomes of including abbreviated period DMI in the
model with the weaning weight gain measurements showed that the model using 10 d
of intake (RFI WW_10) was the least correlated with the control measures. The
model with 60 d of intake had the largest correlation with the control measures.
The fewest measured intake days coupled with the weaning weight values providing
acceptable predictive value was RFI_WW_40, being highly correlated with the
control measures. As established in the literature, at least 70 d is required to
accurately measure ADG. However, we conclude that a shorter period, possibly as
few as 40 d is needed to accurately estimate DMI for a reliable calculation of
RFI.
PMID- 26440034
TI - Stocking rate and monensin supplemental level effects on growth performance of
beef cattle consuming warm-season grasses.
AB - The objective of this study was to evaluate the effects of monensin
supplementation on animals receiving warm-season grass with limited
supplementation. In Exp. 1, treatments were a factorial combination of 2 stocking
rates (1.2 and 1.7 animal unit [AU] [500 kg BW]/ha) and supplementation with
monensin (200 mg/d) or control (no monensin) distributed in a complete randomized
design with 3 replicates. Thirty Angus * Brahman crossbred heifers (Bos taurus *
Bos indicus) with initial BW of 343 +/- 8 kg were randomly allocated into 12
bahiagrass (Paspalum notatum) pastures and supplemented with 0.4 kg DM of
concentrate (14% CP and 78% TDN) daily for 86 d. Herbage mass (HM) and nutritive
value evaluations were conducted every 14 d, and heifers were weighed every 28 d.
There was no effect (P >= 0.97) of monensin on HM, herbage allowance (HA), and
ADG; however, animals receiving monensin had greater (P = 0.03) plasma urea
nitrogen (PUN) concentrations. The stocking rate treatments had similar HM in
June (P = 0.20) and July (P = 0.18), but the higher stocking rate decreased (P <
0.01) HM and HA during August and September. Average daily gain was greater (P <
0.01) for the pastures with the lower stocking rate in August but not different
in July and September (P >= 0.15). Gain per hectare tended to be greater on
pastures with the higher stocking rate (P <= 0.06). In Exp. 2, treatments were 3
levels of monensin (125, 250, and 375 mg/animal per day) and control (no
monensin) tested in a 4 * 4 Latin square with a 10-d adaptation period followed
by 5 d of rumen fluid collection and total DMI evaluation. Blood samples were
collected on d 4 and 5 of the collection period. Ground stargrass (Cynodon
nlemfuensis) hay (11.0% CP and 52% in vitro digestible organic matter) was
offered daily. The steers received the same supplementation regimen as in Exp. 1.
Total DMI was not different among treatments (P = 0.64). There was a linear
increase (P <= 0.01) in propionate and a tendency for decreased acetate (P <=
0.09) concentrations in the rumen with increasing levels of monensin; however,
there was no effect (P >= 0.19) of monensin levels on ruminal pH and ruminal
concentrations of butyrate and ammonia. In addition, there was no effect (P >=
0.73) of monensin levels on plasma concentrations of glucose, insulin, IGF-1, and
PUN. In summary, monensin supplementation effects were not detected at either
stocking rate and may not be effective in increasing performance of beef cattle
grazing low-quality warm-season grasses with limited supplementation.
PMID- 26440035
TI - Elk (Cervus Canadensis) preference for feeds varying in selenium concentration.
AB - Selenium-accumulator plants are reputed to be unpalatable to large ungulates. Elk
(Cervus canadensis) populations in southeastern Idaho overlap with populations of
Se-rich plants, but there is no information on the influence of plant Se
concentration on elk dietary preferences. The objective of this study was to
determine, under controlled conditions, the preference of elk for feeds varying
in Se concentrations. Seven yearling female elk (128 +/- 5 kg) were purchased
from a commercial elk farm in southeastern Idaho and adapted to low-Se alfalfa
pellets. Three feeding trials using pellets with predetermined Se concentrations
were conducted. Alfalfa pellets were commercially made with the addition of
Symphyotrichum ascendens (western aster) so that the pellets contained 0.4, 5,
20, 50, or 100 mg/kg (DM basis) Se. In trial 1, 5 Se-containing alfalfa pellets
(0.4, 5, 20, 50, and 100 mg/kg Se) were offered for 10 d; trial 2 used 4 Se
containing alfalfa pellet choices (0.4, 20, 50, and 100 mg/kg), and trial 3 used
3 pellet choices (0.4, 50, and 100 mg/kg) for 6 d. In trial 1, consumption of the
control pellets by elk was greater than each of the other pellet choices (P <
0.001). Similarly, consumption of the 5-mg/kg Se pellet differed from control
pellet and all other Se-containing pellets (P < 0.0001). There were no
differences (P > 0.50) in consumption of the 20-, 50-, or 100-mg/kg Se pellets.
In trial 2, elk consumed more (P < 0.0001) of the control pellet than the 20-, 50
, and 100-mg/kg Se pellets. Similarly, elk consumed more (P < 0.0001) of the 20
mg/kg Se pellet than the 50- and 100-mg/kg Se pellets. There were no differences
(P > 0.99) in elk consumption of the 50- and 100-mg/kg Se pellets. In trial 3,
elk consumption of the control and 50- and 100-mg/kg Se pellets differed (P <=
0.03) from one another each day except that on d 1 and 2, where elk consumption
of the 50- and 100-mg/kg Se pellets did not differ (P >= 0.32). Elk clearly
discriminated against pellets with the highest Se concentrations when they were
given pellets with differing Se concentrations. These results suggest that elk
are not likely to select forages with high Se concentrations, particularly when
high-Se plants are present in a rangeland situation with numerous other forage
choices.
PMID- 26440036
TI - Effects of glycerin concentration in steam-flaked corn-based diets with
supplemental yellow grease on performance and carcass characteristics of
finishing beef steers.
AB - Forty-eight individually fed crossbred steers (initial BW = 381 +/- 7.61 kg) were
used to determine the effects of glycerin (GLY) concentration in steam-flaked
corn (SFC)-based diets with added yellow grease on animal performance and carcass
characteristics. Glycerin was included at 0, 2.5, 5, and 10% dietary DM replacing
SFC. A completely randomized design was used with steers as the experimental
unit, and the model included the fixed effects of diet. Contrast statements were
used to determine linear and quadratic effects of GLY inclusion. Final BW and DMI
were not affected (P > 0.27) by GLY concentration. Average daily gain and G:F
based on live BW did not differ as GLY level increased in the diet from 0 to 10%
of DM (P > 0.33). Carcass-adjusted final BW and carcass-adjusted G:F were also
not affected by GLY concentration (P > 0.22); however, carcass-adjusted ADG
tended to respond quadratically by decreasing from 2.5 to 5% GLY inclusion and
increasing thereafter (P = 0.10). Calculated dietary NEm and NEg did not differ
as GLY increased in the diet (P > 0.37). Hot carcass weight tended to respond
quadratically, decreasing from 2.5 to 5% GLY and increasing thereafter (P =
0.10). Likewise, dressing percentage tended to respond quadratically by
decreasing from 2.5 to 5% GLY inclusion and increasing to 10% GLY inclusion (P =
0.09). Fat thickness decreased linearly as GLY inclusion increased in the diet (P
< 0.01); however, no differences were detected in marbling score and LM area (P >
0.21). Calculated yield grade (YG) decreased linearly as GLY increased in the
diet from 0 to 10% of DM (P = 0.04). Based on our results, there was no animal
performance benefit for replacing SFC with GLY in diets containing yellow grease,
and the only change in carcass merit was a slight improvement in YG.
PMID- 26440037
TI - Assessing adaptive immune response phenotypes in Australian Holstein-Friesian
heifers in a pasture-based production system.
AB - The objective of this study was to determine the repeatability of ranking
Holstein-Friesian heifers reared in an Australian pasture-based production system
for immune responses (IR) when ranking was based on secondary versus tertiary IR.
Further objectives were to investigate associations between IR and stress
responsiveness, ADG and resistance to internal parasites. A total of 100 heifers
were IR phenotyped at 5 to 6 mo of age and again at 12 to 13 mo of age using
commercial vaccine antigens to induce measurable IR. Antibody production to
tetanus toxoid (TT) was used to assess antibody-mediated IR (AMIR), and delayed
type hypersensitivity reactions to vaccine antigens were used to assess cell
mediated IR (CMIR). Changes in serum cortisol and haptoglobin were used to assess
stress responsiveness and fecal egg counts used as a measure of resistance to
internal parasites. Based on testing, animals were categorized as either average
to above-average (High) or low responders for IR. Secondary and tertiary AMIR
were well correlated (r = 0.651, adjusted R(2) = 0.418, P < 0.0001), whereas
correlations between secondary and tertiary CMIR were poor (r = 0.078, R(2) =
0.004, P = 0.450). A Cohen kappa (kappa) test of agreement was used to test the
consistency of ranking of individual animal for IR and, therefore, the ability to
consistently identify low immune responder animals within the herd across test
periods. The consistency of ranking (High versus low) was moderately high for
AMIR (kappa = 0.445), poor for CMIR (kappa = -0.055), and fair to moderate for
combined IR (kappa = 0.395). High AMIR phenotype animals had significantly higher
serum cortisol concentrations than their low immune responder counterparts (P =
0.045). A similar relationship was observed in heifers categorized for CMIR, with
High CMIR responders having higher serum cortisol concentrations than their low
responder counterparts (P = 0.008). High AMIR calves had a higher ADG compared
with low AMIR calves (0.72 +/- 0.02 versus 0.66 +/- 0.06 kg/d; P = 0.009). Serum
haptoglobin concentrations and worm egg counts were very low and could not be
used to investigate associations with immune responsiveness. It is concluded that
secondary and tertiary antibody responses to TT were well correlated in the
Holstein-Friesian heifers in this study and that by using the testing procedure
described here, low antibody responders were able to be consistently identified
in the herd.
PMID- 26440038
TI - The flipped classroom stimulates greater learning and is a modern 21st century
approach to teaching today's undergraduates.
AB - Many classrooms in higher education still rely on a transformative approach to
teaching where students attend lectures and earn course grades through
examination. In the modern age, traditional lectures are argued by some as
obsolete and do not address the learning needs of today's students. An emerging
pedagogical approach is the concept of the flipped classroom. The flipped
classroom can simply be described as students viewing asynchronous video lectures
on their own and then engaging in active learning during scheduled class times.
In this study, we examined the flipped classroom teaching environment on student
learning gains in an Introduction to Equine Science course. Students (n = 130)
were asked to view 7.5 h of recorded lectures divided into 8 learning modules,
take online quizzes to enforce lecture viewing, take 3 in-class exams, and
prepare to participate in active learning during scheduled class times. Active
learning approaches included individual activities, paired activities, informal
small groups, and large group activities. When compared to students in the
traditional lecture format in earlier years, students in the flipped format
scored higher on all 3 exams (P < 0.05), with both formats taught by the same
instructor. Analysis of ACT scores demonstrated no intellectual capacity
differences between the student populations. To evaluate any gains in critical
thinking, flipped format students were asked to take the Cornell Critical
Thinking Exam (version X). Scores improved from the pretest (50.8 +/- 0.57) to
the posttest (54.4 +/- 0.58; P < 0.01). In the flipped course, no correlations
were found with student performance and interactions with online content.
Students were asked in class to evaluate their experiences based on a 5-point
Likert scale: 1 (strongly disagree) to 5 (strongly agree). The flipped classroom
was ranked as an enjoyable learning experience with a mean of 4.4 +/- 0.10, while
students responded positively to other pointed questions. In formal course
evaluations, flipped format students ranked the following higher (P < 0.05):
instructor availability to assist students; encouragement of independent,
creative, and critical thinking; and amount learned. Overall, the flipped
classroom proved to be a positive learning experience for students. As the
classroom continues to modernize, pedagogical approaches such as the flipped
classroom should be considered for many lecture-style courses taught in the
animal sciences.
PMID- 26440039
TI - Low efficacy of tobramycin in experimental Staphylococcus aureus endocarditis.
AB - The empiric treatment of infective endocarditis (IE) varies widely and, in some
places, a regimen of penicillin in combination with an aminoglycoside is
administered. The increasing incidence of Staphylococcus aureus IE, poor tissue
penetration by aminoglycosides and low frequency of penicillin-susceptible S.
aureus may potentially lead to functional tobramycin monotherapy. Therefore, this
study aimed to evaluate tobramycin monotherapy in an experimental S. aureus IE
rat model. Catheter-induced IE at the aortic valves were established with S.
aureus (NCTC 8325-4) and rats were randomised into untreated (n = 22) or
tobramycin-treated (n = 13) groups. The treatment group received tobramycin once
daily. Animals were evaluated at 1 day post infection (DPI), 2 DPI or 3 DPI.
Quantitative bacteriology and cytokine expression were measured for valves,
myocardium and serum. A decrease of bacterial load was observed in valves and the
spleens of the treated (n = 6) compared to the untreated group at 2 DPI (n = 8)
(p <= 0.02 and p <= 0.01, respectively), but not at 3 DPI (n = 7). Quantitative
bacteriology in the myocardium was not different between the groups. Keratinocyte
derived chemokine (KC) in the aortic valves was significantly reduced at 2 DPI in
the tobramycin-treated group (p <= 0.03). However, the expression of interleukin
(IL)-1b, IL-6 and granulocyte-colony stimulating factor (G-CSF) in the valves was
not different between the two groups. In the myocardium, a significant reduction
in IL-1b was observed at 2 DPI (p <= 0.001) but not at 3 DPI. Tobramycin as
functional monotherapy only reduced bacterial load and inflammation transiently,
and was insufficient in most cases of S. aureus IE.
PMID- 26440040
TI - Molecular seasonal, age and gender distributions of Cryptosporidium in diarrhoeic
Egyptians: distinct endemicity.
AB - Cryptosporidiosis is a worldwide gastrointestinal disease caused by the protozoan
Cryptosporidium parasite. It has a broad range of seasonal and age-related
prevalence. We aimed to study the molecular prevalence and seasonality of
Cryptosporidium over a period of 1 year in a cohort of Egyptian diarrhoeic
patients. Stool samples were collected from 865 diarrhoeic patients attending
outpatient clinics of Cairo University hospitals, from all age groups over a 12
month period, examined microscopically for faecal Cryptosporidium oocysts by the
acid-fast staining method and for copro-DNA detection using nested polymerase
chain reaction (nPCR) assays. PCR-positive samples were characterised molecularly
by nPCR-restriction fragment length polymorphism (RFLP) to determine
Cryptosporidium genotypes. Cryptosporidium copro-DNA was detected in 19.5% of the
collected samples throughout the year, with a major peak in summer (August) and a
small rise in spring (April). Infection was mainly C. hominis (95.8%) followed by
C. parvum (3.0%), affecting all age groups, with predominance in the pre-school
age group, and decrease with age. There were statistically significant
associations between the detection of Cryptosporidium and season, diarrhoea,
patient age and drinking water, while gender, contact with animals and presence
of mucus in stool showed no association. Cryptosporidium in diarrhoeic Egyptians
was of distinct endemicity, with the bi-model mostly influenced by population
dynamics, with a clear high prevalence in pre-school children and predominating
anthroponotic (C. hominis) transmission throughout the year. The obtained results
highlight Cryptosporidium as a water contaminant and an important cause of health
problems in Egypt, necessitating further studies of the risk factors.
PMID- 26440042
TI - Insulin-like growth factor I and risk of incident cancer in elderly men - results
from MrOS (Osteoporotic Fractures in Men) in Sweden.
AB - OBJECTIVE: Studies of the association between circulating IGF-I and cancer risk
have shown conflicting results. We have previously observed a U-shaped
association between IGF-I and cancer mortality. This study test the hypotheses of
a U-shaped association between IGF-I and incident cancer. DESIGN: Elderly men
(2368), randomly recruited from the general community. METHODS: IGF-I was
measured in a cohort of elderly men. Complete data for incident cancer were
obtained from the Swedish Cancer Registry. Statistical analyses included Cox
proportional hazards regressions with or without a spline approach. RESULTS:
Three hundred and sixty-nine participants had incident cancer after baseline.
Prostate cancer was most frequent (n = 140). There was no association between
serum IGF-I and all cancer or prostate cancer incidence. However, there was a
nonlinear association between IGF-I and nonprostate cancer incidence (P = <0.05).
Exploratory analyses were performed for low and high serum IGF-I (quintiles 1 and
5) vs intermediate (quintiles 2-4, referent). There was a tendency of increased
nonprostate cancer risk in men with high IGF-I (HR = 1.26, 95% confidence
interval (CI): 0.92-1.71, P = 0.15). After excluding participants with follow-up
of less than 2.6 years (half median follow-up time), to control for potential
diagnostic delay, the association was statistically significant (HR = 1.55, CI:
1.03-2.35). CONCLUSION: There was a significant nonlinear association between IGF
I and nonprostate cancer. No association between IGF-I and prostate cancer was
observed. Future studies are warranted to further investigate this nonlinear
association, including whether IGF-I concentration is a reproducible, and useful,
risk marker of nonprostate cancer.
PMID- 26440041
TI - Clostridium difficile infection in patients with liver disease: a review.
AB - Over the past two decades, there has been a dramatic worldwide increase in both
the incidence and severity of Clostridium difficile infection (CDI). Paralleling
the increased incidence of CDI in the general population, there has been
increased interest in CDI among patients with liver disease, particularly in
those with liver cirrhosis and post liver transplantation. MEDLINE and several
other electronic databases from January 1995 to December 2014 were searched in
order to identify potentially relevant literature. Patients with cirrhosis and
liver transplant recipients are at high risk for the development CDI because of
antibiotics and proton pump inhibitors use, frequent and prolonged
hospitalization, immunosuppressant therapy, and multiple comorbidities. Enzyme
immunoassay to detect C. difficile toxins A and B in stool remains the most
widely used test for CDI diagnosis, although, more recently, polymerase chain
reaction (PCR)-based assays have become the preferred diagnostic test in many
laboratories. Metronidazole and vancomycin, given orally, have proved to be
effective in the treatment of CDI. Both cirrhotic patients and liver transplant
recipients with CDI have longer length of hospital stay, increased mortality, and
higher healthcare costs than those without CDI. A rapid diagnosis and adequate
therapy of CDI are of paramount importance to improve liver disease patients'
outcome. The aim of this review is to provide up-to-date information on the
epidemiology, risk factors, pathogenesis, treatment, and outcomes in liver
disease patients with CDI.
PMID- 26440043
TI - Poly(ADP-ribosyl)ation is involved in pro-survival autophagy in porcine
blastocysts.
AB - Poly(ADP-ribosyl)ation (PARylation) prevents apoptosis through its involvement in
pro-survival autophagy in cultured cells; whether or not the same is true for pre
implantation embryos has not yet been documented. In this study, we investigated
the participation of PARylation and autophagy in in vitro porcine pre
implantation embryo development. The transcript levels of autophagy-related genes
and poly(ADP-ribose) polymerase 1 (PARP1), an enzyme required for PARylation,
were transiently up-regulated by fertilization, decreased at the late 1-cell
stage, and maintained until the blastocyst stage. LC3, a marker of
autophagosomes, and poly(ADP-ribose) (PAR) polymer were present in all stages of
pre-implantation development. Exposure of embryos to 3-methyladenine, an
autophagy inhibitor, or 3-aminobenzamide, a PARP inhibitor, suppressed the
development of blastocysts. Pharmacological inhibition of PARylation further
suppressed pro-survival autophagy by decreasing the expression of autophagy
related genes (ATG5, BECLIN1, and LC3) and decreasing LC3 protein abundance while
increasing the rate of apoptosis in blastocysts. Deficiency in autophagy also
induced abnormal accumulation of SQSTM1/p62 aggregates in porcine blastocysts.
Collectively, these data suggest that PARylation is involved in selective
autophagic degradation of ubiquitinated proteins, functioning in a pro-survival
role, in porcine in vitro-produced embryos. These pro-survival regulatory
mechanisms may be important for the control of embryo quality.
PMID- 26440044
TI - Predictors of successful weight reduction and maintenance in obese children and
adolescents.
PMID- 26440046
TI - Chondroitin Sulfate Glycosaminoglycan Hydrogels Create Endogenous Niches for
Neural Stem Cells.
AB - Neural stem cells (NSCs) possess great potential for neural tissue repair after
traumatic injuries to the central nervous system (CNS). However, poor survival
and self-renewal of NSCs after injury severely limits its therapeutic potential.
Sulfated chondroitin sulfate glycosaminoglycans (CS-GAGs) linked to CS
proteoglycans (CSPGs) in the brain extracellular matrix (ECM) have the ability to
bind and potentiate trophic factor efficacy, and promote NSC self-renewal in
vivo. In this study, we investigated the potential of CS-GAG hydrogels composed
of monosulfated CS-4 (CS-A), CS-6 (CS-C), and disulfated CS-4,6 (CS-E) CS-GAGs as
NSC carriers, and their ability to create endogenous niches by enriching specific
trophic factors to support NSC self-renewal. We demonstrate that CS-GAG hydrogel
scaffolds showed minimal swelling and degradation over a period of 15 days in
vitro, absorbing only 6.5 +/- 0.019% of their initial weight, and showing no
significant loss of mass during this period. Trophic factors FGF-2, BDNF, and
IL10 bound with high affinity to CS-GAGs, and were significantly (p < 0.05)
enriched in CS-GAG hydrogels when compared to unsulfated hyaluronic acid (HA)
hydrogels. Dissociated rat subventricular zone (SVZ) NSCs when encapsulated in CS
GAG hydrogels demonstrated ~88.5 +/- 6.1% cell viability in vitro. Finally, rat
neurospheres in CS-GAG hydrogels conditioned with the mitogen FGF-2 demonstrated
significantly (p < 0.05) higher self-renewal when compared to neurospheres
cultured in unconditioned hydrogels. Taken together, these findings demonstrate
the ability of CS-GAG based hydrogels to regulate NSC self-renewal, and
facilitate growth factor enrichment locally.
PMID- 26440045
TI - Self-Assembled DNA Immunonanoflowers as Multivalent CpG Nanoagents.
AB - Synthetic unmethylated cytosine-guanine (CpG) oligodeoxynucleotides are
immunostimulatory motifs that have shown promise as vaccines or adjuvants for
diseases such as cancers and infectious diseases. In the present work, novel
immuno-nanoflowers (NFs), self-assembled from long DNA integrated with tandem CpG
through rolling circle replication, were developed for efficient CpG delivery and
protection from nuclease degradation. In a model of macrophage-like cells, the
CpG NFs proved to be potent immunostimulators by triggering the proliferation of
these immune cells, which, in turn, secreted immunostimulatory cytokines,
including tumor necrosis factor alpha, interleukin-6, and interleukin-10. These
results demonstrate the ability of CpG NFs to induce cancer cell apoptosis and
necrosis.
PMID- 26440047
TI - Engineered Adhesion Peptides for Improved Silicon Adsorption.
AB - Engineering peptides that present selective recognition and high affinity for a
material is a major challenge for assembly-driven elaboration of complex systems
with wide applications in the field of biomaterials, hard-tissue regeneration,
and functional materials for therapeutics. Peptide-material interactions are of
vital importance in natural processes but less exploited for the design of novel
systems for practical applications because of our poor understanding of
mechanisms underlying these interactions. Here, we present an approach based on
the synthesis of several truncated peptides issued from a silicon-specific
peptide recovered via phage display technology. We use the photonic response
provided by porous silicon microcavities to evaluate the binding efficiency of 14
different peptide derivatives. We identify and engineer a short peptide sequence
(SLVSHMQT), revealing the highest affinity for p(+)-Si. The molecular recognition
behavior of the obtained peptide fragment can be revealed through mutations
allowing identification of the preferential affinity of certain amino acids
toward silicon. These results constitute an advance in both the engineering of
peptides that reveal recognition properties for silicon and the understanding of
biomolecule-material interactions.
PMID- 26440048
TI - Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult
Melanocyte Stem Cells.
AB - MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and
melanoma physiology. We show that MITF associates the NURF chromatin-remodelling
factor in melanoma cells. ShRNA-mediated silencing of the NURF subunit BPTF
revealed its essential role in several melanoma cell lines and in untransformed
melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate
overlapping gene expression programs in cell lines in vitro. Somatic and specific
inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf
regulates their proliferation, migration and morphology. Once born, Bptf-mutant
mice display premature greying where the second post-natal coat is white. This
second coat is normally pigmented by differentiated melanocytes derived from the
adult melanocyte stem cell (MSC) population that is stimulated to proliferate and
differentiate at anagen. An MSC population is established and maintained
throughout the life of the Bptf-mutant mice, but these MSCs are abnormal and at
anagen, give rise to reduced numbers of transient amplifying cells (TACs) that do
not express melanocyte markers and fail to differentiate into mature melanin
producing melanocytes. MSCs display a transcriptionally repressed chromatin state
and Bptf is essential for reactivation of the melanocyte gene expression program
at anagen, the subsequent normal proliferation of TACs and their differentiation
into mature melanocytes.
PMID- 26440049
TI - Alpha-linolenic acid regulates Cox2/VEGF/MAP kinase pathway and decreases the
expression of HPV oncoproteins E6/E7 through restoration of p53 and Rb expression
in human cervical cancer cell lines.
AB - Cervical cancer represents the largest cause of mortality in women worldwide. In
our previous report, we have shown how alpha-linolenic acid (ALA), an omega-3
fatty acid, regulated the growth of cervical cancer cells. The present study
aimed to explore mechanistic details for the anticancer activity of ALA in
cervical cancer cell lines, SiHa and HeLa. ALA significantly modulated the growth
kinetics of the cells and reduced cell migration with concomitant decrease in the
expression of VEGF, MMP-2, and MMP-9 proteins. Besides this, ALA significantly
decreased the expression of phosphorylated p38, pERK1/2, c-JUN, NFkappaB, and
COX2, proteins. Most importantly, ALA reduced the expression of HPV onco-proteins
E6 and E7, resulting into restoration of expression of tumor suppressor proteins,
p53 and Rb. These results suggested that ALA could be explored for its
therapeutic potential in cervical cancer.
PMID- 26440050
TI - Differential function and regulation of orphan nuclear receptor TR3 isoforms in
endothelial cells.
AB - TR3 has been reported to be an excellent target for angiogenesis therapies. We
reported three TR3 transcript variant messenger RNAs (mRNAs) are expressed in
human umbilical vein endothelial cell (HUVEC) and are differentially regulated by
vascular endothelial growth factor (VEGF). TR3 transcript variant 1 (TR3-TV1) and
variant 2 (TR3-TV2) encoding the same TR3 isoform 1 protein (TR3-iso1) that was
named TR3 has been extensively studied. However, the function of TR3 isoform 2
protein (TR3-iso2) encoded by TR3 transcript variant 3 (TR3-TV3) is still not
known. Here, we clone and express the novel TR3-iso2 protein and find that
expression of TR3-iso2, in contrast to TR3-iso1, inhibits endothelial cell
proliferation induced by VEGF-A, histamine, and phorbol-12-myristate-13-acetate
(PMA). The differential function of TR3-iso2 correlates with the down-regulation
of cyclin D1. However, TR3-iso2 plays similar roles in endothelial cell migration
and monolayer permeability as TR3-iso1. We further demonstrate that several
intracellular signaling pathways are involved in histamine-induced TR3 transcript
variants, including histamine receptor H1-mediated phospholipase C (PLC)/calcium
/calcineurin/protein kinase C (PKC)/protein kinase D (PKD) pathway and ERK
pathway, as well as histamine receptor H3-mediated PKC-ERK pathway. Further,
expressions of TR3-TV1, TR3-TV2, and TR3-TV3 by VEGF and histamine are regulated
by different promoters, but not by their mRNA stability.
PMID- 26440051
TI - HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent
mechanism.
AB - The monocyte-macrophage lineage shows a high degree of diversity and plasticity.
Once they infiltrate tissues, they may acquire two main functional phenotypes,
being known as the classically activated type 1 macrophages (M1) and the
alternative activated type 2 macrophages (M2). The M1 phenotype can be induced by
bacterial products and interferon-gamma and exerts a cytotoxic effect on cancer
cells. Conversely, the alternatively activated M2 phenotype is induced by Il
4/IL13 and promotes tumor cell growth and vascularization. Although receptor for
advanced glycation end-products (RAGE) engagement in M1 macrophages has been
reported by several groups to promote inflammation, nothing is known about the
functionality of RAGE in M2 macrophages. In the current study, we demonstrate
that RAGE is equally expressed in both macrophage phenotypes and that RAGE
activation by high-mobility group protein box1 (HMGB1) promotes protumoral
activities of M2 macrophages. MKN45 cells co-cultured with M2 macrophages treated
with HMGB1 at different times displayed higher invasive abilities. Additionally,
conditioned medium from HMGB1-treated M2 macrophages promotes angiogenesis in
vitro. RAGE-targeting knockdown abrogates these activities. Overall, the present
findings suggest that HMGB1 may contribute, by a RAGE-dependent mechanism, to the
protumoral activities of the M2 phenotype.
PMID- 26440053
TI - Thermodynamic Analysis of Allosteric and Chelate Cooperativity in Di- and
Trivalent Ammonium/Crown-Ether Pseudorotaxanes.
AB - A detailed thermodynamic analysis of the axle-wheel binding in di- and trivalent
secondary ammonium/[24]crown-8 pseudorotaxanes is presented. Isothermal titration
calorimetry (ITC) data and double mutant cycle analyses reveal an interesting
interplay of positive as well as negative allosteric and positive chelate
cooperativity thus providing profound insight into the effects governing
multivalent binding in these pseudorotaxanes.
PMID- 26440054
TI - Polymorphism of MDM2 promoter 309 (rs 2279744) and the risk of PCOS.
AB - This study aimed at evaluating possible association between MDM2 SNP309
polymorphism (rs 2279744) and polycystic ovary syndrome (PCOS). One hundred and
twenty-five women with PCOS and two hundred and fifty women without PCOS were
collected from the department of reproductive medicine of college hospital in
this case-control study. Peripheral blood samples were collected from all
participants and DNA was extracted, MDM2 SNP309 polymorphism (rs 2279744) was
determined from the 125 cases and 250 controls. Women were grouped into PCOS (n =
125) group and control group (n = 250). Odds ratios (OR) and 95% confidence
intervals (CI) were used to evaluate the association between MDM2 SNP309
polymorphism (rs 2279744) and PCOS. The distribution of T allele was significant
higher in PCOS cases than controls. MDM2 SNP 309 T allele is associated with
PCOS.
PMID- 26440052
TI - miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1.
AB - Astrocytoma is one of the most common primary central nervous system tumors and
has both high mortality and a poor 5-year survival rate. MicroRNAs (miRNAs) play
important roles in carcinogenesis by acting on multiple signaling pathways.
Although we have demonstrated that miR-137 is downregulated in astrocytoma
tissues, the role of miR-137 in astrocytoma still remains unknown. In the present
study, we aimed to investigate the function of miR-137 and its possible target
genes in astrocytoma. miR-137 was significantly downregulated in astrocytoma
tissues, and its expression level was inversely correlated with the clinical
stage. Restoring miR-137 was able to dramatically inhibit cell proliferation,
migration, and invasion and enhance apoptosis in vitro, whereas silencing its
expression inhibited these processes. By overexpressing or inhibiting miR-137 in
cancer cells, we experimentally confirmed that miR-137 directly recognized the 3'
UTR (3'-untranslated region) of the RASGRF1 (Ras protein-specific guanine
nucleotide-releasing factor 1) transcript and regulated RASGRF1 expression.
Furthermore, an inverse correlation was observed between miR-137 levels and
RASGRF1 protein levels, but not mRNA levels, in astrocytoma samples. The
silencing of RASGRF1 resulted in similar effects to miR-137 restoration in cancer
cells. Finally, overexpression of RASGRF1 rescued the inhibitory effects of miR
137. Taken together, our results indicate that miR-137 acts as a tumor suppressor
in astrocytoma by targeting RASGRF1. These findings suggest that miR-137 may
serve as a novel therapeutic target in astrocytoma treatment.
PMID- 26440055
TI - Durability of direct immunofluorescence (DIF) slides stored at room temperature.
AB - BACKGROUND: Prior studies suggested that direct immunofluorescence (DIF) slides
can be stored at room temperature. OBJECTIVES: We sought to determine the
durability of DIF slides stored at room temperature for 5 years. METHODS: This
was a retrospective study of 83 DIF slides archived at room temperature during
2010. The pattern of immunoreactants was compared with those noted in the
original report. RESULTS: Loss of reactivity was limited to cases with weak
fluorescence at original diagnosis. Loss of IgG was noted in 12.5% of cases, IgA
in 12%, C3 in 10%, and IgM in 9.75%. Fibrin showed no loss of reactivity.
Preservation of immunofluorescence was not related to site of deposition.
Overall, a reliable diagnosis could be made in 75 of 79 archived cases (94.9%).
LIMITATIONS: Cases had been archived for periods varying from 4.5 to 5 years.
Variations in processing and fluorochromes could affect durability. We have no
way of knowing how long slides had been exposed to ultraviolet light at the time
of initial examination. CONCLUSION: DIF showed excellent durability in slides
kept at room temperature for 5 years.
PMID- 26440057
TI - Docking-based classification models for exploratory toxicology studies on high
quality estrogenic experimental data.
AB - BACKGROUND: The ethical and practical limitation of animal testing has recently
promoted computational methods for the fast screening of huge collections of
chemicals. RESULTS: The authors derived 24 reliable docking-based classification
models able to predict the estrogenic potential of a large collection of
chemicals provided by the US Environmental Protection Agency. Model performances
were challenged by considering AUC, EF1% (EFmax = 7.1), -LR (at sensitivity =
0.75); +LR (at sensitivity = 0.25) and 37 reference compounds comprised within
the training set. Moreover, external predictions were made successfully on ten
representative known estrogenic chemicals and on a set consisting of >32,000
chemicals. CONCLUSION: The authors demonstrate that structure-based methods,
widely applied to drug discovery programs, can be fairly adapted to exploratory
toxicology studies.
PMID- 26440056
TI - Local and systemic responses following intravitreous injection of AAV2-encoded
modified Volvox channelrhodopsin-1 in a genetically blind rat model.
AB - We previously designed a modified channelrhodopsin-1 (mVChR1) protein chimera
with a broader action than that of Chlamydomonas channelrhodopsin-2 and reported
that its transduction into retinal ganglion cells can restore visual function in
genetically blind, dystrophic Royal College of Surgeons (RCS) rats, with
photostimuli ranging from 486 to 640 nm. In the current study, we sought to
investigate the safety and influence of mVChR1 transgene expression. Adeno
associated virus type 2 encoding mVChR1 was administered by intravitreous
injection into dystrophic RCS rats. Reverse-transcription PCR was used to monitor
virus and transgene dissemination and the results demonstrated that their
expression was restricted specifically within the eye tissues, and not in non
target organs. Moreover, examination of the blood, plasma and serum revealed that
no excess immunoreactivity was present, as determined using standard clinical
hematological parameters. Serum antibodies targeting the recombinant adeno
associated virus (rAAV) capsid increased after the injection; however, no
increase in mVChR1 antibody was detected during the observation period. In
addition, retinal histological examination showed no signs of inflammation in
rAAV-injected rats. In conclusion, our results demonstrate that mVChR1 can be
exogenously expressed without harmful immunological reactions in vivo. These
findings will aid in studies of AAV gene transfer to restore vision in late-stage
retinitis pigmentosa.
PMID- 26440058
TI - A three-dimensional skin equivalent reflecting some aspects of in vivo aged skin.
AB - Human skin undergoes morphological, biochemical and functional modifications
during the ageing process. This study was designed to produce a 3-dimensional
(3D) skin equivalent in vitro reflecting some aspects of in vivo aged skin.
Reconstructed skin was generated by co-culturing skin fibroblasts and
keratinocytes on a collagen-glycosaminoglycan-chitosan scaffold, and ageing was
induced by the exposition of fibroblasts to Mitomycin-C (MMC). Recently published
data showed that MMC treatment resulted in a drug-induced accelerated senescence
(DIAS) in human dermal fibroblast cultures. Next to established ageing markers,
histological changes were analysed in comparison with in vivo aged skin. In aged
epidermis, the filaggrin expression is reduced in vivo and in vitro. Furthermore,
in dermal tissue, the amount of elastin and collagen is lowered in aged skin in
vivo as well as after the treatment of 3D skin equivalents with MMC in vitro. Our
results show histological signs and some aspects of ageing in a 3D skin
equivalent in vitro, which mimics aged skin in vivo.
PMID- 26440059
TI - Molecular Magnetic Resonance Imaging of Tumor Response to Therapy.
AB - Personalized cancer medicine requires measurement of therapeutic efficacy as
early as possible, which is optimally achieved by three-dimensional imaging given
the heterogeneity of cancer. Magnetic resonance imaging (MRI) can obtain images
of both anatomy and cellular responses, if acquired with a molecular imaging
contrast agent. The poor sensitivity of MRI has limited the development of
activatable molecular MR contrast agents. To overcome this limitation of
molecular MRI, a novel implementation of our caspase-3-sensitive nanoaggregation
MRI (C-SNAM) contrast agent is reported. C-SNAM is triggered to self-assemble
into nanoparticles in apoptotic tumor cells, and effectively amplifies molecular
level changes through nanoaggregation, enhancing tissue retention and spin
lattice relaxivity. At one-tenth the current clinical dose of contrast agent, and
following a single imaging session, C-SNAM MRI accurately measured the response
of tumors to either metronomic chemotherapy or radiation therapy, where the
degree of signal enhancement is prognostic of long-term therapeutic efficacy.
Importantly, C-SNAM is inert to immune activation, permitting radiation therapy
monitoring.
PMID- 26440060
TI - DC-SIGN expression on podocytes and its role in inflammatory immune response of
lupus nephritis.
AB - Podocytes, the main target of immune complex, participate actively in the
development of glomerular injury as immune cells. Dendritic cell-specific
intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is an innate
immune molecular that has an immune recognition function, and is involved in
mediation of cell adhesion and immunoregulation. Here we explored the expression
of DC-SIGN on podocytes and its role in immune and inflammatory responses in
lupus nephritis (LN). Expression of DC-SIGN and immunoglobulin (Ig)G1 was
observed in glomeruli of LN patients. DC-SIGN was co-expressed with nephrin on
podocytes. Accompanied by increased proteinuria of LN mice, DC-SIGN and IgG1
expressions were observed in the glomeruli from 20 weeks, and the renal function
deteriorated up to 24 weeks. Mice with anti-DC-SIGN antibody showed reduced
proteinuria and remission of renal function. After the podocytes were stimulated
by serum of LN mice in vitro, the expression of DC-SIGN, major histocompatibility
complex (MHC) class II and CD80 was up-regulated, stimulation of T cell
proliferation was enhanced and the interferon (IFN)-gamma/interleukin (IL)-4
ratio increased. However, anti-DC-SIGN antibody treatment reversed these events.
These results suggested that podocytes in LN can exert DC-like function through
their expression of DC-SIGN, which may be involved in immune and inflammatory
responses of renal tissues. However, blockage of DC-SIGN can inhibit immune
functions of podocytes, which may have preventive and therapeutic effects.
PMID- 26440061
TI - Micronized cellular adipose matrix as a therapeutic injectable for diabetic
ulcer.
AB - BACKGROUND: Despite the clinical potential of adipose-derived stem/stromal cells
(ASCs), there are some clinical difficulties due to the regulation of cell
therapies. MATERIALS & METHODS: Micronized cellular adipose matrix (MCAM)
injectable was prepared through selective extraction of connective tissue
fractions in fat tissue only through mechanical minimal manipulation procedures.
RESULTS: It retained some capillaries and ASCs, but most adipocytes were removed.
The presence of viable ASCs, vascular endothelial cells was confirmed and ASCs of
MCAM kept intact mesenchymal differentiation capacity. In diabetic mice, skin
wounds treated with MCAM showed significantly accelerated healing compared with
phosphate-buffered saline-treated ones. CONCLUSION: The proven potential of MCAM
to accelerate healing in ischemic diabetic ulcers may offer a simple, safe and
minimally invasive means for tissue repair and revitalization.
PMID- 26440062
TI - Development and Implementation of Team-Based Panel Management Tools: Filling the
Gap between Patient and Population Information Systems.
AB - Effective team-based models of care, such as the Patient-Centered Medical Home,
require electronic tools to support proactive population management strategies
that emphasize care coordination and quality improvement. Despite the spread of
electronic health records (EHRs) and vendors marketing population health tools,
clinical practices still may lack the ability to have: (1) local control over
types of data collected/reports generated, (2) timely data (eg, up-to-date data,
not several months old), and accordingly (3) the ability to efficiently monitor
and improve patient outcomes. This article describes a quality improvement
project at the hospital system level to develop and implement a flexible panel
management (PM) tool to improve care of subpopulations of patients (eg, panels of
patients with diabetes) by clinical teams. An in-depth case analysis approach is
used to explore barriers and facilitators in building a PM registry tool for team
based management needs using standard data elements (eg, laboratory values,
pharmacy records) found in EHRs. Also described are factors that may contribute
to sustainability; to date the tool has been adapted to 6 disease-focused
subpopulations encompassing more than 200,000 patients. Two key lessons emerged
from this initiative: (1) though challenging, team-based clinical end users and
information technology needed to work together consistently to refine the
product, and (2) locally developed population management tools can provide
efficient data tracking for frontline clinical teams and leadership. The
preliminary work identified critical gaps that were successfully addressed by
building local PM registry tools from EHR-derived data and offers lessons learned
for others engaged in similar work. (Population Health Management 2016;19:232
239).
PMID- 26440063
TI - Phosphorylation Alters Oestrogen Receptor beta-Mediated Transcription in
Neurones.
AB - Nuclear steroid hormone receptors are ubiquitously expressed transcription
factors whose activity can be altered by post-translational modifications, such
as phosphorylation. The consequences of post-translational modifications have
been described for several members of the nuclear steroid hormone receptor
superfamily; however, little is known about the effects of oestrogen receptor
(ER)beta phosphorylation in the brain. Moreover, to our knowledge, the presence
of phosphorylated ERbeta has not been detected in the brain of any species to
date. Oestrogen receptor beta is highly expressed in several regions of the brain
and in vitro studies have demonstrated that it can be phosphorylated at two
serine residues (S87 and S105) in the N-terminal AF-1 region. The present study
aimed to determine whether phosphorylated ERbeta is detectable in the hippocampus
of aged female rats, as well as the functional consequences of ERbeta S87 and
S105 phosphorylation on transcriptional activity in neuronal cells. First, we
used a novel PhosTag(TM) approach to detect phosphorylated forms of ERbeta in the
dorsal hippocampus of aged female rats. The data obtained demonstrated abundant
forms of phosphorylated ERbeta in the dorsal hippocampus, suggesting that this
post-translational modification might be an important regulator of ERbeta
function. To assess the functional consequences of ERbeta phosphorylation in
neuronal cells, we created phospho-mimetic (S87E, S105E) and phospho-null (S87A,
S105A) ERbeta receptors that were transiently transfected in a hippocampal
derived cell line. Collectively, our results showed that phosphorylation of S87
and S105 altered both ligand-independent and ligand-dependent ERbeta
transcriptional regulation. Overall, these data demonstrate that phosphorylated
forms of ERbeta are present in the brain of aged female rats and that
phosphorylation of ERbeta could differentially alter ERbeta-mediated gene
expression.
PMID- 26440064
TI - Identification of functional networks associated with cell death in the retina of
OXYS rats during the development of retinopathy.
AB - Age-related macular degeneration (AMD) is a major cause of blindness in developed
countries, and the molecular pathogenesis of early events in AMD is poorly
understood. Senescence-accelerated OXYS rats develop AMD-like retinopathy. The
aim of this study was to explore the differences in retinal gene expression
between OXYS and Wistar (control) rats at age 20 d and to identify the pathways
of retinal cell death involved in the OXYS retinopathy initiation and
progression. Retinal mRNA profiles of 20-day-old OXYS and Wistar rats were
generated at the sequencing read depth 40 mln, in triplicate, using Illumina
GAIIx. A terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
nick end labeling (TUNEL) assay was performed to measure the apoptosis level.
GeneMANIA was used to construct interaction networks for differentially expressed
(DE) apoptosis-related genes at ages 20 d and 3 and 18 months. Functional
analysis was suggestive of a developmental process, signal transduction, and cell
differentiation as the most enriched biological processes among 245 DE genes at
age 20 d An increased level of apoptosis was observed in OXYS rats at age 20 d
but not at advanced stages. We identified functional clusters in the constructed
interaction networks and possible hub genes (Rasa1, cFLAR, Birc3, Cdk1, Hspa1b,
Erbb3, and Ntf3). We also demonstrated the significance of the extrinsic
apoptotic pathway at preclinical, early, and advanced stages of retinopathy
development. Besides the cell death signaling pathways, immune system-related
processes and lipid-metabolic processes showed overrepresentation in the clusters
of all networks. These characteristics of the expression profile of the genes
functionally associated with apoptosis may contribute to the pathogenesis of AMD
like retinopathy in senescence-accelerated OXYS rats.
PMID- 26440065
TI - Biobanking of patient and patient-derived xenograft ovarian tumour tissue:
efficient preservation with low and high fetal calf serum based methods.
AB - Using patient-derived xenografts (PDXs) for preclinical cancer research demands
proper storage of tumour material to facilitate logistics and to reduce the
number of animals needed. We successfully established 45 subcutaneous ovarian
cancer PDXs, reflecting all histological subtypes, with an overall take rate of
68%. Corresponding cells from mouse replaced human tumour stromal and endothelial
cells in second generation PDXs as demonstrated with mouse-specific vimentin and
CD31 immunohistochemical staining. For biobanking purposes two cryopreservation
methods, a fetal calf serum (FCS)-based (95%v/v) "FCS/DMSO" protocol and a low
serum-based (10%v/v) "vitrification" protocol were tested. After primary
cryopreservation, tumour take rates were 38% and 67% using either the
vitrification or FCS/DMSO-based cryopreservation protocol, respectively.
Cryopreserved tumour tissue of established PDXs achieved take rates of 67% and
94%, respectively compared to 91% using fresh PDX tumour tissue. Genotyping
analysis showed that no changes in copy number alterations were introduced by any
of the biobanking methods. Our results indicate that both protocols can be used
for biobanking of ovarian tumour and PDX tissues. However, FCS/DMSO-based
cryopreservation is more successful. Moreover, primary engraftment of fresh
patient-derived tumours in mice followed by freezing tissue of successfully
established PDXs is the preferred way of efficient ovarian cancer PDX biobanking.
PMID- 26440066
TI - RNA-seq is a valuable complement of conventional diagnostic tools in newly
diagnosed AML patients.
PMID- 26440067
TI - Genetic changes correlate with histopathology in a benign, borderline and
malignant mucinous ovarian tumour.
PMID- 26440068
TI - Effects of Exposure to WwTW Effluents over Two Generations on Sexual Development
and Breeding in Roach Rutilus rutilus.
AB - Exposure to environmental estrogens in wastewater treatment works (WwTW)
effluents induces feminized responses in male fish, including the development of
eggs in male testes. However, the impacts on the offspring of exposed fish are
not well understood. In this study, we examined whether roach (Rutilus rutilus)
from mothers that had been exposed to an undiluted WwTW effluent from early life
to sexual maturity had altered susceptibility to gonadal feminization and an
impaired capacity to reproduce. For males from both WwTW effluent exposed mothers
and dilution water exposed mothers, effluent exposure for up to 3 years and 9
months induced feminized male gonads, although the intersex condition was
relatively mild. There was no difference in the severity of gonadal feminization
in roach derived from either WwTW effluent exposed or dilution water exposed
mothers. Furthermore, a breeding study revealed that roach with effluent-exposed
mothers reproduced with an equal success as roach with mothers exposed to clean
water. Roach exposed to the effluent for 3 years in this study were able to
reproduce successfully. Our findings provide no evidence for impacts of WwTW
effluent exposure on reproduction or gonadal disruption in roach down the female
germ line and add to existing evidence that male roach with a mild intersex
condition are able to breed competitively.
PMID- 26440069
TI - Efficient mass transport by optical advection.
AB - Advection is critical for efficient mass transport. For instance, bare diffusion
cannot explain the spatial and temporal scales of some of the cellular processes.
The regulation of intracellular functions is strongly influenced by the transport
of mass at low Reynolds numbers where viscous drag dominates inertia. Mimicking
the efficacy and specificity of the cellular machinery has been a long time
pursuit and, due to inherent flexibility, optical manipulation is of particular
interest. However, optical forces are relatively small and cannot significantly
modify diffusion properties. Here we show that the effectiveness of microparticle
transport can be dramatically enhanced by recycling the optical energy through an
effective optical advection process. We demonstrate theoretically and
experimentally that this new advection mechanism permits an efficient control of
collective and directional mass transport in colloidal systems. The cooperative
long-range interaction between large numbers of particles can be optically
manipulated to create complex flow patterns, enabling efficient and tunable
transport in microfluidic lab-on-chip platforms.
PMID- 26440070
TI - Biosignatures across Space and Time-Special Collection.
PMID- 26440072
TI - Strain-tuned optoelectronic properties of hollow gallium sulphide microspheres.
AB - Sulfide semiconductors have attracted considerable attention. The main challenge
is to prepare materials with a designable morphology, a controllable band
structure and optoelectronic properties. Herein, we report a facile chemical
transportation reaction for the synthesis of Ga2S3 microspheres with novel hollow
morphologies and partially filled volumes. Even without any extrinsic dopant,
photoluminescence (PL) emission wavelength could be facilely tuned from 635 to
665 nm, depending on its intrinsic inhomogeneous strain distribution. Geometric
phase analysis (GPA) based on high-resolution transmission electron microscopy
(HRTEM) imaging reveals that the strain distribution and the associated PL
properties can be accurately controlled by changing the growth temperature
gradient, which depends on the distance between the boats used for raw material
evaporation and microsphere deposition. The stacking-fault density, lattice
distortion degree and strain distribution at the shell interfacial region of the
Ga2S3 microspheres could be readily adjusted. Ab initio first-principles
calculations confirm that the lowest conductive band (LCB) is dominated by S-3s
and Ga-4p states, which shift to the low-energy band as a result of the
introduction of tensile strain, well in accordance with the observed PL
evolution. Therefore, based on our strain driving strategy, novel guidelines
toward the reasonable design of sulfide semiconductors with tunable
photoluminescence properties are proposed.
PMID- 26440071
TI - Community centrality and social science research.
AB - Community centrality is a growing requirement of social science. The field's
research practices are increasingly expected to conform to prescribed
relationships with the people studied. Expectations about community centrality
influence scholarly activities. These expectations can pressure social scientists
to adhere to models of community involvement that are immediate and that include
community-based co-investigators, advisory boards, and liaisons. In this context,
disregarding community centrality can be interpreted as failure. This paper
considers evolving norms about the centrality of community in social science. It
problematises community inclusion and discusses concerns about the impact of
community centrality on incremental theory development, academic integrity,
freedom of speech, and the value of liberal versus communitarian knowledge.
Through the application of a constructivist approach, this paper argues that
social science in which community is omitted or on the periphery is not failed
science, because not all social science requires a community base to make a
genuine and valuable contribution. The utility of community centrality is not
necessarily universal across all social science pursuits. The practices of
knowing within social science disciplines may be difficult to transfer to a
community. These practices of knowing require degrees of specialisation and
interest that not all communities may want or have.
PMID- 26440073
TI - GM1-Modified Lipoprotein-like Nanoparticle: Multifunctional Nanoplatform for the
Combination Therapy of Alzheimer's Disease.
AB - Alzheimer's disease (AD) exerts a heavy health burden for modern society and has
a complicated pathological background. The accumulation of extracellular beta
amyloid (Abeta) is crucial in AD pathogenesis, and Abeta-initiated secondary
pathological processes could independently lead to neuronal degeneration and
pathogenesis in AD. Thus, the development of combination therapeutics that can
not only accelerate Abeta clearance but also simultaneously protect neurons or
inhibit other subsequent pathological cascade represents a promising strategy for
AD intervention. Here, we designed a nanostructure,
monosialotetrahexosylganglioside (GM1)-modified reconstituted high density
lipoprotein (GM1-rHDL), that possesses antibody-like high binding affinity to
Abeta, facilitates Abeta degradation by microglia, and Abeta efflux across the
blood-brain barrier (BBB), displays high brain biodistribution efficiency
following intranasal administration, and simultaneously allows the efficient
loading of a neuroprotective peptide, NAP, as a nanoparticulate drug delivery
system for the combination therapy of AD. The resulting multifunctional
nanostructure, alphaNAP-GM1-rHDL, was found to be able to protect neurons from
Abeta(1-42) oligomer/glutamic acid-induced cell toxicity better than GM1-rHDL in
vitro and reduced Abeta deposition, ameliorated neurologic changes, and rescued
memory loss more efficiently than both alphaNAP solution and GM1-rHDL in AD model
mice following intranasal administration with no observable cytotoxicity noted.
Taken together, this work presents direct experimental evidence of the rational
design of a biomimetic nanostructure to serve as a safe and efficient
multifunctional nanoplatform for the combination therapy of AD.
PMID- 26440074
TI - Evaluation of Pistacia lentiscus seed oil and phenolic compounds for in vitro
antiproliferative effects against BHK21 cells.
AB - CONTEXT: Within the global context of increasing cancer diseases, natural
products are important in devising new drugs and providing unique ideas in cancer
therapy. In Tunisian folk medicine, Pistacia lentiscus L. (Anacardiaceae) fixed
oil is used for cancer treatment. OBJECTIVE: This investigation studied, for the
first time, the antiproliferative effect of Pistacia lentiscus fixed oil and its
phenolic extract on BHK21 cancer cells. MATERIALS AND METHODS: Oil was extracted
from fruits harvested in northwest Tunisia and the phenolic fraction was obtained
by mixing with methanol. The anti-proliferative activity of the two tested
substances on BHK 21 cells were investigated in vitro using trypan blue assays.
Cells were treated with different concentrations of P. lentiscus oil (0.009,
0.018, 0.036, and 0.09 g/mL) and the phenolic extract (0.007, 0.014, 0.03, and
0.07 g/mL) for 24, 48, and 72 h. RESULTS: The inhibitory effect of Pistacia
lentiscus fixed oil increases with the increase in dose. The IC50 value was
estimated at 0.029 g/mL. The percentage of cell viability was 42.46 +/- 3.4% at a
dose of 0.09 g/mL and was significantly lower than that of the untreated control
(96.24 +/- 2.5%, p<0.01). The phenolic extract demonstrated a dose- and time
dependent inhibitory effect on BHK21 cell growth. After 48 h of incubation, the
IC50 value was estimated at 0.15 g/mL. DISCUSSION AND CONCLUSION: The results
demonstrated the potential of Pistacia lentiscus fixed oil in treating cancer, as
it is used in traditional medicine.
PMID- 26440075
TI - Rethinking inheritance, yet again: inheritomes, contextomes and dynamic
phenotypes.
AB - In recent years, there have been many calls for an extended evolutionary
synthesis, based in part upon growing evidence for nongenetic mechanisms of
inheritance, i.e., similarities in phenotype between parents and offspring that
are not due to shared genes. While there has been an impressive marshalling of
evidence for diverse forms of nongenetic inheritance (epigenetic, ecological,
behavioural and symbolic), there have been relatively few studies trying to
integrate the different forms of inheritance into a common conceptual structure,
a development that would be important to formalize elements of the extended
evolutionary synthesis. Here, we propose a framework for an extended view of
inheritance and introduce some conceptual distinctions that we believe, are
important to this issue. In this framework, the phenotype is conceived of as a
dynamic entity, its state, at any point in time resulting from intertwined
effects of previous phenotypic state, and of hereditary materials (DNA and
otherwise) and environment. We contrast our framework with the standard gene
based view of inheritance, and also discuss our framework in the specific context
of recent attempts to accommodate nongenetic inheritance within the framework of
classical quantitative genetics and the Price equation. In particular, we believe
that the extended view of inheritance and effects on the phenotype developed here
is particularly well-suited to individual-based simulation studies of
evolutionary dynamics. The results of such simulations, in turn, could be useful
for assessing, how well extended models based on quantitative genetics or the
Price equation perform at capturing complex evolutionary dynamics.
PMID- 26440076
TI - Genomewide identification, classification and analysis of NAC type gene family in
maize.
AB - NAC transcription factors comprise a large plant-specific gene family. Increasing
evidence suggests that members of this family have diverse functions in plant
growth and development. In this study, we performed a genomewide survey of NAC
type genes in maize (Zea mays L.). A complete set of 148 nonredundant NAC genes
(ZmNAC1-ZmNAC148) were identifiedin the maize genome using Blast search tools,
and divided into 12 groups (a-l) based on phylogeny. Chromosomal location of
these genes revealed that they are distributed unevenly across all 10
chromosomes. Segmental and tandem duplication contributed largely to the
expansion of the maize NAC gene family. The Ka/Ks ratio suggested that the
duplicated genes of maize NAC family mainly experienced purifying selection, with
limited functional divergence after duplication events.Microarray analysis
indicated most of the maize NAC genes were expressed across different
developmental stages. Moreover,19 maize NAC genes grouped with published stress
responsive genes from other plants were found to contain putative stress
responsive cis-elements in their promoter regions. All these stress-responsive
genes belonged to the group d (stress-related).Further, these genes showed
differential expression patterns over time in response to drought treatments by
quantitative real-time PCR analysis. Our results reveal a comprehensive overview
of the maize NAC, and form the foundation for future functional research to
uncover their roles in maize growth and development.
PMID- 26440077
TI - Biallelic expression of Tssc4, Nap1l4, Phlda2 and Osbpl5 in adult cattle.
AB - Genomic imprinting of the Cdkn1c/Kcnq1ot1 region shows lack of conservation
between human and mouse. This region has been reported to be associated with
Beckwith-Wiedemann syndrome (BWS) and cancer. To increase our understanding of
imprinted genes in bovine Cdkn1c/Kcnq1ot1 imprinting cluster, we assessed the
imprinting status of four cattle genes (Tssc4,Nap1l4, Phlda2 and Osbpl5) in seven
types of tissues: heart, liver, spleen, lung, kidney, skeletal muscle and
subcutaneous fat using polymorphism-based sequencing approach. It was found that
all the four genes showed biallelic expression in tissues in which transcripts
were detected. Nap1l4 and Tssc4 were detected in all examined tissues, while the
expression of Phlda2 and Osbpl5 was tissue-specific. Phlda2 was not detected in
heart and subcutaneous fat, and Osbpl5 was not detected in spleen and skeletal
muscle. In addition, identification of species-specific imprinted genes is
necessary to understand the evolution of genomic imprinting and to elucidate
mechanisms leading to allele-specific expression.
PMID- 26440078
TI - Transcriptome analysis reveals dynamic changes in the gene expression of tobacco
seedlings under low potassium stress.
AB - Potassium plays a key role in plant development and reproduction. In agricultural
practice, potassium deficiency is common worldwide, and leads to crop growth
inhibition and output reduction. In this study, we analysed the transcriptome of
tobacco seedlings under low potassium stress. Tobacco seedlings with or without
decreased potassium treatment were harvested after 0 (control), 6, 12, or 24 h
and were submitted for microarray analysis. The results showed that up to 3790
genes were upregulated or downregulated more than 2-fold as a result of the
decreased potassium treatment. Gene ontology analysis revealed significantly
differentially expressed genes that were categorized as cation binding,
transcription regulation, metabolic processes, transporter activity and enzyme
regulation. Some potassium, nitrogen and phosphorus transporters; transcription
factors; and plant signal molecules, such as CPKs were also significantly
differentially expressed under potassium deficiency. Our results indicate that
the expression profiles of a large number of genes involved in various plant
physiological processes are significantly altered in response to potassium
deficiency, which can result in physiological and morphological changes in
tobacco plants.
PMID- 26440079
TI - The commonly used eye-specific sev-GAL4 and GMR-GAL4 drivers in Drosophila
melanogaster are expressed in tissues other than eyes also.
AB - The binary GAL4-UAS system of conditional gene expression is widely used by
Drosophila geneticists to target expression of the desired transgene in tissue of
interest. In many studies, a preferred target tissue is the Drosophila eye, for
which the sev-GAL4 and GMR-GAL4 drivers are most widely used since they are
believed to be expressed exclusively in the developing eye cells. However,
several reports have noted lethality following expression of certain transgenes
under these GAL4 drivers notwithstanding the fact that eye is not essential for
survival of the fly. Therefore, to explore the possibility that these drivers may
also be active in tissues other than eye, we examined the expression of UAS-GFP
reporter driven by the sev-GAL4 or GMR-GAL4 drivers. We found that both these
drivers are indeed expressed in additional tissues, including a common set of
specific neuronal cells in larval and pupal ventral and cerebral ganglia. Neither
sev nor glass gene has so far been reported to be expressed in these neuronal
cells. Expression pattern of sev-GAL4 driver parallels that of the endogenous
Sevenless protein. In addition to cells in which sev-GAL4 is expressed, the GMR
GAL4 is expressed in several other larval cell types also. Further, two different
GMR-GAL4 lines also show some specific differences in their expression domains
outside the eye discs. These findings emphasize the need for a careful
confirmation of the expression domains of a GAL4 driver being used in a given
study, rather than relying only on the empirically claimed expression domains.
PMID- 26440080
TI - Molecular characterization of zeta class glutathione S-transferases from Pinus
brutia Ten.
AB - Glutathione transferases (GSTs; EC 2.5.1.18) play important roles in stress
tolerance and metabolic detoxification in plants.In higher plants, studies on
GSTs have focussed largely on agricultural plants. There is restricted
information about molecular characterization of GSTs in gymnosperms. To date,
only tau class GST enzymes have been characterized from some pinus species. For
the first time, the present study reports cloning and molecular characterization
of two zeta class GST genes, namely PbGSTZ1 and PbGSTZ2 from Pinus brutia Ten.,
which is an economically important pine native to the eastern Mediterranean
region and have to cope with several environmental stress conditions. The PbGSTZ1
gene was isolated from cDNA, whereas PbGSTZ2 was isolated from genomic DNA.
Sequence analysis of PbGSTZ1 and PbGSTZ2 revealed the presence of an open reading
frame of 226 amino acids with typical consensus sequences of the zeta class plant
GSTs. Protein and secondary structure prediction analysis of two zeta class
PbGSTZs have shared common features of other plant zeta class GSTs. Genomic
clone, PbGSTZ2 gene, is unexpectedly intronless. Extensive sequence analysis of
PbGSTZ2, with cDNA clone, PbGSTZ1, revealed 87% identity at nucleotide and 81%
identity at amino acid levels with 41 amino acids differences suggesting that
genomic PbGSTZ2 gene might be an allelic or a paralogue version of PbGSTZ1.
PMID- 26440082
TI - Generation and characterization of Brassica rapa ssp. pekinensis - B. oleracea
var. capitata monosomic and disomic alien addition lines.
AB - Five monosomic alien addition lines (MAALs) of Brassica rapa ssp. pekinensis - B.
oleracea var. capitata were obtained by hybridization and backcrossing between B.
rapa ssp. pekinensis (female parent) and B. oleracea var. capitata. The alien
linkage groups were identified using 42 B. oleracea var. capitata linkage group
specific markers as B. oleracea linkage groups C2, C3, C6, C7 and C8. Based on
the chromosomal karyotype of root tip cells, these five MAALs added individual
chromosomes from B. oleracea var. capitata: chr 1 (the longest), chr 2 or 3, chr
5 (small locus of 25S rDNA), chr 7 (satellite-carrying) and chr 9 (the shortest).
Five disomic alien addition lines were then generated by selfing their
corresponding MAALs.
PMID- 26440081
TI - In planta transformation of sorghum (Sorghum bicolor (L.) Moench) using TPS1 gene
for enhancing tolerance to abiotic stresses.
AB - An in planta transformation protocol for sorghum (Sorghum bicolor (L.) Moench)
using shoot apical meristem of germinating seedlings is reported in this study.
Agrobacterium tumefaciens strain, LBA4404 with pCAMBIA1303 vector and construct
pCAMBIA1303TPS1 were individually used for transformation. Since, the transgene
is integrated into the cells of already differentiated tissues, the T 0 plants
were chimeric and stable integration was observed in T1 generation. beta
Glucuronidase (GUS) expression in the seedlings and spikelets of emerging cob was
the first indication of transformability in T0 generation which was further
confirmed by PCR analysis using hpt and TPS1 gene-specific primers. Screening on
25 mg/L hygromycin combined with PCR analysis was used for selection of
transformants in the T1 generation. Transformation efficiencies ranged between 34
38% and 26-34% using pCAMBIA1303 vector and construct pCAMBIA1303TPS1,
respectively. Molecular characterization of the T2 transgenics using PCR, RT-PCR
and Southern blot analyses further revealed the integration, expression and
inheritance of the transgene. These results indicate the feasibility of the
method to generate transgenics with pCAM-BIA1303 vector and construct
pCAMBIA1303TPS1. The abiotic stress tolerance of TPS1 transgenics developed in
the present study was evident by the ability of the transformants to tolerate 200
mM NaCl as well as higher root growth and biomass.
PMID- 26440083
TI - Map-based cloning and expression analysis of BMR-6 in sorghum.
AB - Brown midrib mutants in sorghum are associated with reduced lignin content and
increased cell wall digestibility. In this study, we characterized a bmr-6
sorghum mutant, which shows reddish pigment in the midrib and stem after the
fifth-leaf stage. Compared to wild type, Kalson lignin content of bmr-6 is
decreased significantly. We used histological analysis to determine that the
mutant exhibited a modified pattern of lignin staining and found an increased
polysaccharide content. We cloned BMR-6 gene, a gene encoded a cinnamyl alcohol
dehydrogenase (CAD), using a map-based cloning approach. Genetic complementation
confirmed that CAD is responsible for the BMR-6 phenotype. BMR-6 gene was
expressed in all tested sorghum tissues, with the highest being in midrib and
stem. Transient expression assays in Nicotiana benthamiana leaves demonstrated
cytomplasmic localization of BMR-6. We found that the expression level of bmr-6
was significantly decreased in the mutant but expression of SbCAD3 and SbCAD5
were significantly increased. Our results indicate that BMR-6 not only affects
the distribution of lignin but also the biosynthesis of lignin in sorghum.
PMID- 26440084
TI - Molecular survey of Tamyb10-1 genes and their association with grain colour and
germinability in Chinese wheat and Aegilops tauschii.
AB - To investigate allelic variation of Myb10-1 genes in Chinese wheat and to examine
its association with germination level in wheat, a total of 582 Chinese bread
wheat cultivars and 110 Aegilops tauschii accessions were used to identify
allelic variations of three Myb10-1 genes. Identification results indicated that
there is a novel Tamyb10-B1 allele, designated Tamyb10-B1c, in the five Chinese
landraces. The Tamyb10-B1c possibly has a large deletion including Tamyb10-B1
gene. There are three novel Tamyb10-D1 alleles (Aetmyb10-D1c, Aetmyb10-D1d and
Aetmyb10-D1e) that were discovered in Aegilops tauschii. Of them, Aetmyb10-D1c
allele possessed a 104-bp deletion and this resulted in a frame shift in the open
reading frame of the Aetmyb10-D1 gene. AETMYB10-D1d and AETMYB10-D1e proteins
possessed three and two different amino acids when compared with TAMYB10-D1b
protein, respectively. Association of Tamyb10-1 allelic variation with grain
germination level indicated that all five allelic combinations with red grains
showed a significantly higher GP (germination percentage) and GI (germination
index) values than those of white-grained Tamyb10-A1a/Tamyb10-B1a/Tamyb10-D1a
genotype after storing it for one year. Moreover, the Tamyb10-A1b/Tamyb10
B1c/Tamyb10-D1b genotype possesses the significantly highest GP and GI among the
six different Tamyb10-1 combinations. This study could provide useful information
for wheat breeding programme in terms of grain colour and germination level.
PMID- 26440086
TI - Association between vitamin D receptor gene polymorphism (TaqI) and obesity in
Chinese population.
PMID- 26440087
TI - A simple route to maximum-likelihood estimates of two-locus recombination
fractions under inequality restrictions.
PMID- 26440085
TI - Gene structure, phylogeny and expression profile of the sucrose synthase gene
family in cacao (Theobroma cacao L.).
AB - In higher plants, sucrose synthase (Sus, EC 2.4.1.13) is widely considered as a
key enzyme involved in sucrose metabolism. Although, several paralogous genes
encoding different isozymes of Sus have been identified and characterized in
multiple plant genomes, to date detailed information about the Sus genes is
lacking for cacao. This study reports the identification of six novel Sus genes
from economically important cacao tree. Analyses of the gene structure and
phylogeny of the Sus genes demonstrated evolutionary conservation in the Sus
family across cacao and other plant species. The expression of cacao Sus genes
was investigated via real-time PCR in various tissues, different developmental
phases of leaf, flower bud and pod. The Sus genes exhibited distinct but
partially redundant expression profiles in cacao, with TcSus1, TcSus5 and TcSus6,
being the predominant genes in the bark with phloem, TcSus2 predominantly
expressing in the seed during the stereotype stage. TcSus3 and TcSus4 were
significantly detected more in the pod husk and seed coat along the pod
development, and showed development dependent expression profiles in the cacao
pod. These results provide new insights into the evolution, and basic information
that will assist in elucidating the functions of cacao Sus gene family.
PMID- 26440088
TI - Two novel mutations in ILDR1 gene cause autosomal recessive nonsyndromic hearing
loss in consanguineous Iranian families.
PMID- 26440089
TI - Novel compound heterozygous frameshift mutations of C2orf37 in a familial Indian
case of Woodhouse-Sakati syndrome.
PMID- 26440090
TI - Sex-specific asymmetry in eye development in interspecific hybrids in the
Drosophila bipectinata species complex.
PMID- 26440091
TI - Characterization of low-molecular-weight glutenin subunit genes of Aegilops
section Sitopsis and comparative analysis with those of wheat (Triticum aestivum
L.) and some Aegilops species.
PMID- 26440092
TI - Genetic variants of retinol-binding protein 4 in adolescents are associated with
liver function and inflammatory markers but not with obesity and insulin
resistance.
PMID- 26440093
TI - Genetic portrait of Lisboa immigrant population from Cabo Verde with
mitochondrial DNA analysis.
PMID- 26440094
TI - Characterization and fine mapping of NGP4c(t), a novel gene controlling the
number of grains per panicle in rice.
PMID- 26440095
TI - Upgrade of Castanea sativa (Mill.) genetic resources by sequencing of barcode
markers.
PMID- 26440096
TI - Plant transcriptomics and responses to environmental stress: an overview.
AB - Different stresses include nutrient deficiency, pathogen attack, exposure to
toxic chemicals etc. Transcriptomic studies have been mainly applied to only a
few plant species including the model plant, Arabidopsis thaliana. These studies
have provided valuable insights into the genetic networks of plant stress
responses. Transcriptomics applied to cash crops including barley, rice,
sugarcane, wheat and maize have further helped in understanding physiological and
molecular responses in terms of genome sequence, gene regulation, gene
differentiation, posttranscriptional modifications and gene splicing. On the
other hand, comparative transcriptomics has provided more information about
plant's response to diverse stresses. Thus, transcriptomics, together with other
biotechnological approaches helps in development of stress tolerance in crops
against the climate change.
PMID- 26440098
TI - Expansion of polyalanine tracts in the QA domain may play a critical role in the
clavicular development of cleidocranial dysplasia.
PMID- 26440097
TI - Genetic epidemiology of coronary artery disease: an Asian Indian perspective.
AB - Coronary artery disease (CAD) has emerged as a major cause of morbidity and
mortality worldwide. Recent findings on the role of genetic factors in the
aetiopathology of CAD have implicated novel genes and variants in addition to
those involved in lipid and lipoprotein metabolism. However, our present
knowledge is limited due to lack of clarity on their exact identity and the
quantum of impact on disease susceptibility, and incident risk. It is a matter of
great interest to understand the role of genetic factors in ethnic populations
that have a strong underlying predisposition to CAD such as the South Asian
populations, particularly among Asian Indians living in India and abroad.
Although, a number of isolated studies do implicate certain gene polymorphisms
towards enhanced disease susceptibility, the available data remains scanty and
inconclusive as they have not been validated in large, prospective cohorts. The
present review aims to consolidate the available literature on the genetics of
CAD in Asian Indians and seeks to provide insights on the concerns that need to
be addressed in future studies to generate information having clinical value.
PMID- 26440100
TI - [Acute dyspnea 8 days after Cesarean section].
PMID- 26440099
TI - [Cardiogenic shock after drug therapy for atrial fibrillation with tachycardia :
Case report of an 89-year-old woman].
AB - beta-Blockers and calcium channel blockers are commonly used drugs in the
treatment of atrial fibrillation with tachycardia. However, in patients with high
myocardial susceptibility and vulnerability, combination therapy with beta
blockers and non-dihydropyridine calcium channel blockers (verapamil or
diltiazem) but also individual administration can cause drug-induced cardiogenic
shock. Thus, the simultaneous administration of beta-blockers and non
dihydropyridine calcium channel blockers is absolutely contraindicated. In case
of acute heart failure, isolated application is also contraindicated. In the
treatment of a cardiogenic shock induced by beta-blockers and/or non
dihydropyridine calcium channel blockers, administration of intravenous calcium,
glucagon or high-dose insulin is recommended.
PMID- 26440101
TI - Correction: Multilevel Approach of a 1-Year Program of Dietary and Exercise
Interventions on Bone Mineral Content and Density in Metabolic Syndrome - the
RESOLVE Randomized Controlled Trial.
PMID- 26440102
TI - A Comparison of Free-Standing versus Co-Located Long-Term Acute Care Hospitals.
AB - BACKGROUND: Long-term acute care hospitals (LTACs) provide specialized treatment
for patients with chronic critical illness. Increasingly LTACs are co-located
within traditional short-stay hospitals rather than operated as free-standing
facilities, which may affect LTAC utilization patterns and outcomes. METHODS: We
compared free-standing and co-located LTACs using 2005 data from the United
States Centers for Medicare & Medicaid Services. We used bivariate analyses to
examine patient characteristics and timing of LTAC transfer, and used propensity
matching and multivariable regression to examine mortality, readmissions, and
costs after transfer. RESULTS: Of 379 LTACs in our sample, 192 (50.7%) were free
standing and 187 (49.3%) were co-located in a short-stay hospital. Co-located
LTACs were smaller (median bed size: 34 vs. 66, p <0.001) and more likely to be
for-profit (72.2% v. 68.8%, p = 0.001) than freestanding LTACs. Co-located LTACs
admitted patients later in their hospital course (average time prior to transfer:
15.5 days vs. 14.0 days) and were more likely to admit patients for ventilator
weaning (15.9% vs. 12.4%). In the multivariate propensity-matched analysis,
patients in co-located LTACs experienced higher 180-day mortality (adjusted
relative risk: 1.05, 95% CI: 1.00-1.11, p = 0.04) but lower readmission rates
(adjusted relative risk: 0.86, 95% CI: 0.75-0.98, p = 0.02). Costs were similar
between the two hospital types (mean difference in costs within 180 days of
transfer: -$3,580, 95% CI: -$8,720 -$1,550, p = 0.17). CONCLUSIONS: Compared to
patients in free-standing LTACs, patients in co-located LTACs experience slightly
higher mortality but lower readmission rates, with no change in overall resource
use as measured by 180 day costs.
PMID- 26440103
TI - Assessing Antigenic Drift of Seasonal Influenza A(H3N2) and A(H1N1)pdm09 Viruses.
AB - Under selective pressure from the host immune system, antigenic epitopes of
influenza virus hemagglutinin (HA) have continually evolved to escape antibody
recognition, termed antigenic drift. We analyzed the genomes of influenza A(H3N2)
and A(H1N1)pdm09 virus strains circulating in Thailand between 2010 and 2014 and
assessed how well the yearly vaccine strains recommended for the southern
hemisphere matched them. We amplified and sequenced the HA gene of 120 A(H3N2)
and 81 A(H1N1)pdm09 influenza virus samples obtained from respiratory specimens
and calculated the perfect-match vaccine efficacy using the pepitope model, which
quantitated the antigenic drift in the dominant epitope of HA. Phylogenetic
analysis of the A(H3N2) HA1 genes classified most strains into genetic clades 1,
3A, 3B, and 3C. The A(H3N2) strains from the 2013 and 2014 seasons showed very
low to moderate vaccine efficacy and demonstrated antigenic drift from epitopes C
and A to epitope B. Meanwhile, most A(H1N1)pdm09 strains from the 2012-2014
seasons belonged to genetic clades 6A, 6B, and 6C and displayed the dominant
epitope mutations at epitopes B and E. Finally, the vaccine efficacy for
A(H1N1)pdm09 (79.6-93.4%) was generally higher than that of A(H3N2). These
findings further confirmed the accelerating antigenic drift of the circulating
influenza A(H3N2) in recent years.
PMID- 26440104
TI - Systematic Characteristic Exploration of the Chimeras Generated in Multiple
Displacement Amplification through Next Generation Sequencing Data Reanalysis.
AB - BACKGROUND: The chimeric sequences produced by phi29 DNA polymerase, which are
named as chimeras, influence the performance of the multiple displacement
amplification (MDA) and also increase the difficulty of sequence data process.
Despite several articles have reported the existence of chimeric sequence, there
was only one research focusing on the structure and generation mechanism of
chimeras, and it was merely based on hundreds of chimeras found in the sequence
data of E. coli genome. METHOD: We finished data mining towards a series of Next
Generation Sequencing (NGS) reads which were used for whole genome haplotype
assembling in a primary study. We established a bioinformatics pipeline based on
subsection alignment strategy to discover all the chimeras inside and achieve
their structural visualization. Then, we artificially defined two statistical
indexes (the chimeric distance and the overlap length), and their regular
abundance distribution helped illustrate of the structural characteristics of the
chimeras. Finally we analyzed the relationship between the chimera type and the
average insertion size, so that illustrate a method to decrease the proportion of
wasted data in the procedure of DNA library construction. RESULTS/CONCLUSION:
131.4 Gb pair-end (PE) sequence data was reanalyzed for the chimeras. Totally,
40,259,438 read pairs (6.19%) with chimerism were discovered among 650,430,811
read pairs. The chimeric sequences are consisted of two or more parts which
locate inconsecutively but adjacently on the chromosome. The chimeric distance
between the locations of adjacent parts on the chromosome followed an approximate
bimodal distribution ranging from 0 to over 5,000 nt, whose peak was at about 250
to 300 nt. The overlap length of adjacent parts followed an approximate Poisson
distribution and revealed a peak at 6 nt. Moreover, unmapped chimeras, which were
classified as the wasted data, could be reduced by properly increasing the length
of the insertion segment size through a linear correlation analysis.
SIGNIFICANCE: This study exhibited the profile of the phi29MDA chimeras by tens
of millions of chimeric sequences, and helped understand the amplification
mechanism of the phi29 DNA polymerase. Our work also illustrated the importance
of NGS data reanalysis, not only for the improvement of data utilization
efficiency, but also for more potential genomic information.
PMID- 26440106
TI - Quantifying the stabilizing effects of protein-ligand interactions in the gas
phase.
AB - The effects of protein-ligand interactions on protein stability are typically
monitored by a number of established solution-phase assays. Few translate readily
to membrane proteins. We have developed an ion-mobility mass spectrometry
approach, which discerns ligand binding to both soluble and membrane proteins
directly via both changes in mass and ion mobility, and assesses the effects of
these interactions on protein stability through measuring resistance to
unfolding. Protein unfolding is induced through collisional activation, which
causes changes in protein structure and consequently gas-phase mobility. This
enables detailed characterization of the ligand-binding effects on the protein
with unprecedented sensitivity. Here we describe the method and software required
to extract from ion mobility data the parameters that enable a quantitative
analysis of individual binding events. This methodology holds great promise for
investigating biologically significant interactions between membrane proteins and
both drugs and lipids that are recalcitrant to characterization by other means.
PMID- 26440105
TI - Using the HISQUI29 to assess the sound quality levels of Spanish adults with
unilateral cochlear implants and no contralateral hearing.
AB - To evaluate cochlear implant (CI) users' self-reported level of sound quality and
quality of life (QoL). Sound quality was self-evaluated using the hearing implant
sound quality index (HISQUI29). HISQUI29 scores were further examined in three
subsets. QoL was self-evaluated using the glasgow benefit inventory (GBI). GBI
scores were further examined in three subsets. Possible correlations between the
HISQUI29 and GBI were explored. Additional possible correlations between these
scores and subjects' pure tone averages, speech perception scores, age at
implantation, duration of hearing loss, duration of CI use, gender, and implant
type were explored. Subjects derived a "moderate" sound quality level from their
CI. Television, radio, and telephone tasks were easier in quiet than in
background noise. 89 % of subjects reported their QoL benefited from having a CI.
Mean total HISQUI29 score significantly correlated with all subcategories of the
GBI. Age at implantation inversely correlated with the total HISQUI29 score and
with television and radio understanding. Sentence in noise scores significantly
correlated with all sound perception scores. Women had a better mean score in
music perception and in telephone use than did men. CI users' self-reported
levels of sound quality significantly correlated with their QoL. Cochlear
implantation had a beneficial impact on subjects' QoL. Understanding speech is
easier in quiet than in noise. Music perception remains a challenge for many CI
users. The HISQUI29 and the GBI can provide useful information about the everyday
effects of future treatment modalities, rehabilitation strategies, and technical
developments.
PMID- 26440107
TI - Violent Death Rates and Risk for Released Prisoners in North Carolina.
AB - Released prisoners face high risk of early mortality. The risk of violent death,
specifically homicide and suicide, are addressed in this study. Data on inmates
released from the North Carolina Division of Adult Corrections (N = 476) matched
to the Violent Death Reporting System are analyzed to estimate rates and
demographic and criminal justice-related predictors. Violent death rates for
persons released from prison were more than 7 times higher than for the general
adult population. Results from multinomial logistic regression indicate decreased
homicide risk for every year of age, whereas male gender and minority race
increased risk. For suicide, minority race, release without supervision, and
substance abuse treatment in prison decreased fatality risk. By contrast, a
history of mental illness increased suicide risk. Implications for practice and
research are discussed.
PMID- 26440108
TI - Consumer Perspectives on Gambling Harm Minimisation Measures in an Australian
Jurisdiction.
AB - This paper investigates consumer perspectives of implemented and proposed
gambling harm minimisation measures taken from a geographically stratified survey
of adult residents in Tasmania, Australia. Electronic gaming machine (EGM)
gamblers were asked whether current and proposed EGM harm minimisation measures
impacted on their actual or anticipated gambling expenditure and enjoyment.
Participants were analysed based on their endorsement of Problem Gambling
Severity Index criteria (scores 0-27), and categorised as non-problem gamblers
(score 0), low-risk gamblers (scores 1-2), and moderate/problem gamblers (scores
3+). Specifically, we wanted to identify harm minimisation policies that resulted
in the lowest decreases in enjoyment for non-problem gamblers and the highest
decreases in expenditure for moderate/problem gamblers. Regarding current
policies, the lowest decrease in enjoyment for non-problem gamblers was the ban
on Automatic Teller Machines (ATMs) in EGM venues (0.2 %) while the highest
decrease in expenditure for moderate/problem gamblers was the reduction in
maximum lines (46.9 %). For the proposed measures, the lowest decrease in
enjoyment for non-problem gamblers was visible clocks (1.2 %) while the highest
decrease in expenditure for moderate/problem gamblers was reducing cash
withdrawals (36.3 %). These results suggest universal EGM harm minimisation
measures can differentially target non-problem and moderate/problem gamblers.
PMID- 26440110
TI - Correction: Temperature-dependent energy levels and size-independent
thermodynamics.
AB - Correction for 'Temperature-dependent energy levels and size-independent
thermodynamics' by Rodrigo de Miguel, Phys. Chem. Chem. Phys., 2015, 17, 15691
15693.
PMID- 26440109
TI - Divergent Evolution of the Transcriptional Network Controlled by Snf1-Interacting
Protein Sip4 in Budding Yeasts.
AB - Cellular responses to starvation are of ancient origin since nutrient limitation
has always been a common challenge to the stability of living systems. Hence,
signaling molecules involved in sensing or transducing information about limiting
metabolites are highly conserved, whereas transcription factors and the genes
they regulate have diverged. In eukaryotes the AMP-activated protein kinase
(AMPK) functions as a central regulator of cellular energy homeostasis. The yeast
AMPK ortholog SNF1 controls the transcriptional network that counteracts carbon
starvation conditions by regulating a set of transcription factors. Among those
Cat8 and Sip4 have overlapping DNA-binding specificity for so-called carbon
source responsive elements and induce target genes upon SNF1 activation. To
analyze the evolution of the Cat8-Sip4 controlled transcriptional network we have
compared the response to carbon limitation of Saccharomyces cerevisiae to that of
Kluyveromyces lactis. In high glucose, S. cerevisiae displays tumor cell-like
aerobic fermentation and repression of respiration (Crabtree-positive) while K.
lactis has a respiratory-fermentative life-style, respiration being regulated by
oxygen availability (Crabtree-negative), which is typical for many yeasts and for
differentiated higher cells. We demonstrate divergent evolution of the Cat8-Sip4
network and present evidence that a role of Sip4 in controlling anabolic
metabolism has been lost in the Saccharomyces lineage. We find that in K. lactis,
but not in S. cerevisiae, the Sip4 protein plays an essential role in C2 carbon
assimilation including induction of the glyoxylate cycle and the carnitine
shuttle genes. Induction of KlSIP4 gene expression by KlCat8 is essential under
these growth conditions and a primary function of KlCat8. Both KlCat8 and KlSip4
are involved in the regulation of lactose metabolism in K. lactis. In chromatin
immunoprecipitation experiments we demonstrate binding of both, KlSip4 and
KlCat8, to selected CSREs and provide evidence that KlSip4 counteracts KlCat8
mediated transcription activation by competing for binding to some but not all
CSREs. The finding that the hierarchical relationship of these transcription
factors differs between K. lactis and S. cerevisiae and that the sets of target
genes have diverged contributes to explaining the phenotypic differences in
metabolic life-style.
PMID- 26440111
TI - A Culture-Behavior-Brain Loop Model of Human Development.
AB - Increasing evidence suggests that cultural influences on brain activity are
associated with multiple cognitive and affective processes. These findings prompt
an integrative framework to account for dynamic interactions between culture,
behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model
of human development that proposes that culture shapes the brain by
contextualizing behavior, and the brain fits and modifies culture via behavioral
influences. Genes provide a fundamental basis for, and interact with, the CBB
loop at both individual and population levels. The CBB loop model advances our
understanding of the dynamic relationships between culture, behavior, and the
brain, which are crucial for human phylogeny and ontogeny. Future brain changes
due to cultural influences are discussed based on the CBB loop model.
PMID- 26440112
TI - Metabolomic Profiling of 13 Diatom Cultures and Their Adaptation to Nitrate
Limited Growth Conditions.
AB - Diatoms are very efficient in their use of available nutrients. Changes in
nutrient availability influence the metabolism and the composition of the cell
constituents. Since diatoms are valuable candidates to search for oil producing
algae, measurements of diatom-produced compounds can be very useful for
biotechnology. In order to explore the diversity of lipophilic compounds produced
by diatoms, we describe the results from an analysis of 13 diatom strains. With
the help of a lipidomics platform, which combines an UPLC separation with a high
resolution/high mass accuracy mass spectrometer, we were able to measure and
annotate 142 lipid species. Out of these, 32 were present in all 13 cultures. The
annotated lipid features belong to six classes of glycerolipids. The data
obtained from the measurements were used to create lipidomic profiles. The
metabolomic overview of analysed cultures is amended by the measurement of 96
polar compounds. To further increase the lipid diversity and gain insight into
metabolomic adaptation to nitrogen limitation, diatoms were cultured in media
with high and low concentrations of nitrate. The growth in nitrogen-deplete or
nitrogen-replete conditions affects metabolite accumulation but has no major
influence on the species-specific metabolomic profile. Thus, the genetic
component is stronger in determining metabolic patterns than nitrogen levels.
Therefore, lipid profiling is powerful enough to be used as a molecular
fingerprint for diatom cultures. Furthermore, an increase of triacylglycerol
(TAG) accumulation was observed in low nitrogen samples, although this trend was
not consistent across all 13 diatom strains. Overall, our results expand the
current understanding of metabolomics diversity in diatoms and confirm their
potential value for producing lipids for either bioenergy or as feed stock.
PMID- 26440113
TI - Surgical Specialty Residents More Likely to Receive the Arnold P. Gold Humanism
and Excellence in Teaching Award.
AB - OBJECTIVE: The Arnold P. Gold Humanism and Excellence in Teaching Awards are
given by medical students to residents. The aim of this study is to evaluate the
distribution of this award based on residency specialty. The hypothesis is that
surgical residents more commonly receive this award. METHODS: This was a
retrospective study from 2004 to 2013. All award recipients were obtained from
the Arnold P. Gold Foundation website. The specialties of award recipients were
tabulated. The number of award winners per thousand specialty residents was
estimated using the Accreditation Council for Graduate Medical Education Data
Resource Book, adjusting for the number of awarding schools and resident
specialties. All statistics used an alpha = 0.05. RESULTS: There were 2489 awards
given during the study period, with 52.6% in medical specialties and 47.4% in
surgical specialties (p = 0.45). The specialties most commonly awarded were
General Surgery (22.3%), Internal Medicine (20.9%), and Obstetrics/Gynecology
(20.4%). Adjusting for the number of eligible residents, there were 59.9
awards/1000 Obstetrics/Gynecology residents, 43.1 awards/1000 General Surgery
residents, and 20.2 awards/1000 Internal Medicine residents (p < 0.001).
CONCLUSION: Controlling for the number of eligible residents, the Arnold P. Gold
Humanism and Excellence in Teaching Awards are more commonly given to surgical
specialty residents.
PMID- 26440114
TI - Interfacial ordering of thermotropic liquid crystals triggered by the secondary
structures of oligopeptides.
AB - We report that assemblies formed by eight oligopeptides at phospholipid-decorated
interfaces of thermotropic liquid crystals (LCs) trigger changes in ordering of
the LCs that are dependent on the secondary structures of the oligopeptides (as
characterized in situ using infrared-visible sum-frequency spectroscopy).
PMID- 26440116
TI - A Farewell to B-Lines: Ageing and Disappearance of Ultrasound Artifacts as a
Diagnostic Tool.
PMID- 26440117
TI - Production of Immunoabsorbent Nanoparticles by Displaying Single-Domain Protein A
on Potato Virus X.
AB - The combination of antibodies with nanoparticles provides wide-ranging
applications in biosensing. While several covalent presentation strategies have
been established, there is need for alternative, non-covalent methods to provide
a routine for scalable nanomanufacturing. We report the multivalent presentation
of the B domain of Staphylococcus aureus protein A (SpAB) on potato virus X (PVX)
nanoparticles. Three different synthetic strategies were used to obtain chimeric
PVX(SpAB) filaments. The protein A fragments displayed on the surface of all
three PVX chimeras remained fully functional as an immunoabsorbent for antibody
capture enabling biosensing. The new biomaterials presented could find
applications as diagnostic tools for biomedical or environmental monitoring.
PMID- 26440115
TI - Computational modeling of cytokine signaling in microglia.
AB - Neuroinflammation due to glial activation has been linked to many CNS diseases.
We developed a computational model of a microglial cytokine interaction network
to study the regulatory mechanisms of microglia-mediated neuroinflammation. We
established a literature-based cytokine network, including TNFalpha, TGFbeta, and
IL-10, and fitted a mathematical model to published data from LPS-treated
microglia. The addition of a previously unreported TGFbeta autoregulation loop to
our model was required to account for experimental data. Global sensitivity
analysis revealed that TGFbeta- and IL-10-mediated inhibition of TNFalpha was
critical for regulating network behavior. We assessed the sensitivity of the LPS
induced TNFalpha response profile to the initial TGFbeta and IL-10 levels. The
analysis showed two relatively shifted TNFalpha response profiles within separate
domains of initial condition space. Further analysis revealed that TNFalpha
exhibited adaptation to sustained LPS stimulation. We simulated the effects of
functionally inhibiting TGFbeta and IL-10 on TNFalpha adaptation. Our analysis
showed that TGFbeta and IL-10 knockouts (TGFbeta KO and IL-10 KO) exert divergent
effects on adaptation. TFGbeta KO attenuated TNFalpha adaptation whereas IL-10 KO
enhanced TNFalpha adaptation. We experimentally tested the hypothesis that IL-10
KO enhances TNFalpha adaptation in murine macrophages and found supporting
evidence. These opposing effects could be explained by differential kinetics of
negative feedback. Inhibition of IL-10 reduced early negative feedback that
results in enhanced TNFalpha-mediated TGFbeta expression. We propose that
differential kinetics in parallel negative feedback loops constitute a novel
mechanism underlying the complex and non-intuitive pro- versus anti-inflammatory
effects of individual cytokine perturbations.
PMID- 26440118
TI - Response to Majid: Neurocognitive and Cultural Approaches to Odor Naming are
Complementary.
PMID- 26440119
TI - Cultural Factors Shape Olfactory Language.
PMID- 26440120
TI - Inhibition, Disinhibition, and the Control of Action in Tourette Syndrome.
AB - Tourette syndrome (TS) is a neurological disorder characterized by vocal and
motor tics. TS is associated with impairments in behavioral inhibition,
dysfunctional signaling of the inhibitory neurotransmitter GABA, and alterations
in the balance of excitatory and inhibitory influences within brain networks
implicated in motor learning and the selection of actions. We review evidence
that increased control over motor outputs, including the suppression of tics, may
develop during adolescence in TS and be accompanied by compensatory,
neuromodulatory, alterations in brain structure and function. In particular, we
argue that increased control over motor outputs in TS is brought about by local
increases in 'tonic' inhibition that lead to a reduction in the 'gain' of motor
excitability.
PMID- 26440121
TI - Imitation and Innovation: The Dual Engines of Cultural Learning.
AB - Imitation and innovation work in tandem to support cultural learning in children
and facilitate our capacity for cumulative culture. Here we propose an integrated
theoretical account of how the unique demands of acquiring instrumental skills
and cultural conventions provide insight into when children imitate, when they
innovate, and to what degree. For instrumental learning, with an increase in
experience, high fidelity imitation decreases and innovation increases. By
contrast, for conventional learning, imitative fidelity stays high, regardless of
experience, and innovation stays low. We synthesize cutting edge research on the
development of imitative flexibility and innovation to provide insight into the
social learning mechanisms underpinning the uniquely human mind.
PMID- 26440122
TI - Decoding Rich Spatial Information with High Temporal Resolution.
AB - New research suggests that magnetoencephalography (MEG) contains rich spatial
information for decoding neural states. Even small differences in the angle of
neighbouring dipoles generate subtle, but statistically separable field patterns.
This implies MEG (and electroencephalography: EEG) is ideal for decoding neural
states with high-temporal resolution in the human brain.
PMID- 26440123
TI - Moral Perception.
AB - Based on emerging research, we propose that human perception is preferentially
attuned to moral content. We describe how moral concerns enhance detection of
morally relevant stimuli, and both command and direct attention. These perceptual
processes, in turn, have important consequences for moral judgment and behavior.
PMID- 26440124
TI - Understanding What We See: How We Derive Meaning From Vision.
AB - Recognising objects goes beyond vision, and requires models that incorporate
different aspects of meaning. Most models focus on superordinate categories
(e.g., animals, tools) which do not capture the richness of conceptual knowledge.
We argue that object recognition must be seen as a dynamic process of
transformation from low-level visual input through categorical organisation to
specific conceptual representations. Cognitive models based on large normative
datasets are well-suited to capture statistical regularities within and between
concepts, providing both category structure and basic-level individuation. We
highlight recent research showing how such models capture important properties of
the ventral visual pathway. This research demonstrates that significant advances
in understanding conceptual representations can be made by shifting the focus
from studying superordinate categories to basic-level concepts.
PMID- 26440125
TI - ER contact sites direct late endosome transport.
AB - Endosomes shuttle select cargoes between cellular compartments and, in doing so,
maintain intracellular homeostasis and enable interactions with the extracellular
space. Directionality of endosomal transport critically impinges on cargo fate,
as retrograde (microtubule minus-end directed) traffic delivers vesicle contents
to the lysosome for proteolysis, while the opposing anterograde (plus-end
directed) movement promotes recycling and secretion. Intriguingly, the
endoplasmic reticulum (ER) is emerging as a key player in spatiotemporal control
of late endosome and lysosome transport, through the establishment of physical
contacts with these organelles. Earlier studies have described how minus-end
directed motor proteins become discharged from vesicles engaged at such contact
sites. Now, Raiborg et al. implicate ER-mediated interactions, induced by
protrudin, in loading plus-end-directed motor kinesin-1 onto endosomes, thereby
stimulating their transport toward the cell's periphery. In this review, we
recast the prevailing concepts on bidirectional late endosome transport and
discuss the emerging paradigm of inter-compartmental regulation from the ER
endosome interface viewpoint.
PMID- 26440126
TI - Sex commonalities and differences in the relationship between resilient
personality and the intrinsic connectivity of the salience and default mode
networks.
AB - Increased resilience is associated with better health outcomes and reduced
morbidity in response to injury and homeostatic perturbations. Proper functioning
of the salience network (SN) and modulation of the default mode network (DMN) by
SN may play a role in adaptively responding to stress. Here, we demonstrate that
resilient personality in healthy subjects is associated with SN and DMN
connectivity patterns and that these patterns are influenced by sex. While
connectivity of SN with several brain regions including right anterior insula was
significantly associated with resilient personality in both men and women,
results suggest that increased functional integration of anterior DMN
preferentially benefits women while increased functional integration of posterior
DMN preferentially benefits men in terms of resilience. These findings may relate
to previous demonstrations that men and women engage different information
processing and behavioral strategies to achieve resilience and highlight the
importance of considering sex in resilience research.
PMID- 26440127
TI - Immune responses to human cancer stem-like cells/cancer-initiating cells.
AB - Cancer stem-like cells (CSC)/cancer-initiating cells (CIC) are defined as minor
subpopulations of cancer cells that are endowed with properties of higher tumor
initiating ability, self-renewal ability and differentiation ability.
Accumulating results of recent studies have revealed that CSC/CIC are resistant
to standard cancer therapies, including chemotherapy, radiotherapy and molecular
targeting therapy, and eradiation of CSC/CIC is, thus, critical to cure cancer.
Cancer immunotherapy is expected to become the "fourth" cancer therapy. Cytotoxic
T lymphocytes (CTL) play an essential role in immune responses to cancers, and
CTL can recognize CSC/CIC in an antigen-specific manner. CSC/CIC express several
tumor-associated antigens (TAA), and cancer testis (CT) antigens are reasonable
sources for CSC/CIC-targeting immunotherapy. In this review article, we discuss
CSC/CIC recognition by CTL, regulation of immune systems by CSC/CIC, TAA
expression in CSC/CIC, and the advantages of CSC/CIC-targeting immunotherapy.
PMID- 26440128
TI - Bowdler spur also found in camptomelic dysplasia.
PMID- 26440130
TI - (14)N NQR, relaxation and molecular dynamics of the explosive TNT.
AB - Multiple pulse sequences are widely used for signal enhancement in NQR detection
applications. Since the various (14)N NQR relaxation times, signal decay times
and frequency of each NQR line have a major influence on detection sequence
performance, it is important to characterise these parameters and their
temperature variation, as fully as possible. In this paper we discuss such
measurements for a number of the nu+ and nu- NQR lines of monoclinic and
orthorhombic TNT and relate the temperature variation results to molecular
dynamics. The temperature variation of the (14)N spin-lattice relaxation times T1
is interpreted as due to hindered rotation of the NO2 group about the C-NO2 bond
with an activation energy of 89 kJ mol(-1) for the ortho and para groups of
monoclinic TNT and 70 kJ mol(-1) for the para group of orthorhombic TNT.
PMID- 26440129
TI - Diagnostic accuracy of point-of-care ultrasound for catheter-related thrombosis
in children.
AB - BACKGROUND: Compared with consultative US performed by the radiology department,
point-of-care US performed by non-radiology physicians can accurately diagnose
deep venous thrombosis in adults. OBJECTIVE: In preparation for a multicenter
randomized controlled trial, we determined the accuracy of point-of-care US in
diagnosing central venous catheter-related thrombosis in critically ill children.
MATERIALS AND METHODS: Children <18 years old with a central venous catheter who
were admitted to the intensive care unit were enrolled. Consultative and point-of
care compression ultrasounds with Doppler were done on the vein where the
catheter was inserted within 24 h after insertion. Repeat US was obtained within
24 h of removal of the catheter. All images were centrally, blindly and
independently adjudicated for thrombosis by a team of pediatric radiologists.
Chance-corrected agreement between readings was calculated. RESULTS: From 84
children, 152 pairs of consultative and point-of-care ultrasounds were analyzed.
A total of 38 (25.0%) consultative and 17 (11.2%) point-of-care ultrasounds were
positive for thrombosis. The chance-corrected agreement between consultative and
point-of-care ultrasounds was 0.17 (standard error: 0.07; P = 0.008). With
consultative US as a reference, the sensitivity of point-of-care US was 28.1%
(95% confidence interval: 13.7%-46.7%) with a specificity of 91.8% (95%
confidence interval: 84.4%-96.4%). A catheter in the subclavian vein was
associated with discordant readings (adjusted odds ratio: 4.00; 95% confidence
interval: 1.45-13.94). CONCLUSION: Point-of-care US, when performed by non
radiology physicians and centrally adjudicated by pediatric radiologists in the
setting of a multicenter randomized controlled trial, may not accurately diagnose
catheter-related thrombosis in critically ill children.
PMID- 26440132
TI - Phenotypic screening: the future of antibody discovery.
AB - Most antibody therapeutics have been isolated from high throughput target-based
screening. However, as the number of validated targets diminishes and the target
space becomes increasingly competitive, alternative strategies, such as
phenotypic screening, are gaining momentum. Here, we review successful phenotypic
screens, including those used to isolate antibodies against cancer and infectious
agents. We also consider exciting advances in the expression and phenotypic
screening of antibody repertoires in single cell autocrine systems. As
technologies continue to develop, we believe that antibody phenotypic screening
will increase further in popularity and has the potential to provide the next
generation of therapeutic antibodies.
PMID- 26440131
TI - Aromatic spectral editing techniques for magic-angle-spinning solid-state NMR
spectroscopy of uniformly (13)C-labeled proteins.
AB - The four aromatic amino acids in proteins, namely histidine, phenylalanine,
tyrosine, and tryptophan, have strongly overlapping (13)C chemical shift ranges
between 100 and 160ppm, and have so far been largely neglected in solid-state NMR
determination of protein structures. Yet aromatic residues play important roles
in biology through pi-pi and cation-pi interactions. To better resolve and assign
aromatic residues' (13)C signals in magic-angle-spinning (MAS) solid-state NMR
spectra, we introduce two spectral editing techniques. The first method uses
gated (1)H decoupling in a proton-driven spin-diffusion (PDSD) experiment to
remove all protonated (13)C signals and retain only non-protonated carbon signals
in the aromatic region of the (13)C spectra. The second technique uses chemical
shift filters and (1)H-(13)C dipolar dephasing to selectively detect the Calpha,
Cbeta and CO cross peaks of aromatic residues while suppressing the signals of
all aliphatic residues. We demonstrate these two techniques on amino acids, a
model peptide, and the microcrystalline protein GB1, and show that they
significantly simplify the 2D NMR spectra and both reveal and permit the ready
assignment of the aromatic residues' signals.
PMID- 26440133
TI - Do Basketball Players Have a High Risk of Pulmonary Embolism? A Scoping Review.
AB - PURPOSE: Pulmonary embolism (PE) is a serious preventable disease that requires
urgent care. In recent years, there have been several reports in the media about
basketball players experiencing PE. The aim of the present study was to assess
whether there is a need for in-depth studies to determine whether basketball
players constitute a group particularly at risk of PE and to describe some
hypotheses to be investigated. METHODS: We reviewed original articles about PE
among professional and amateur basketball players in the scientific literature
(PubMed) and the Internet (Google search) for the seasons 2010-2011 to 2014-2015,
both of which were included. We used search strategies that included some
combination of PE-related terms. Rates of PE were calculated and were compared
with those obtained from other studies. RESULTS: Of the 15 cases detected, the
majority were men (66.7%), mean ages being 28.8 yr among males and 20.4 yr among
females. We focused on six cases which, were detected among National Basketball
Association and Asociacion de Clubes de Baloncesto basketball players, resulting
in an average incidence of 1.27 and 2.06 cases per 1000 players per year in the
National Basketball Association and Asociacion de Clubes de Baloncesto,
respectively. This incidence is much higher than that observed in general
population studies for the same age group. CONCLUSIONS: Basketball players seem
to have a higher risk of PE than their peers from the general population. More
studies are needed to confirm these findings and identify factors predisposing
them to PE to contribute to its prevention.
PMID- 26440134
TI - Comparison of Three Popular Exercise Modalities on VO2max in Overweight and
Obese.
AB - INTRODUCTION: In this prospective randomized trial, we examined the effect of
three popular exercise training modalities on maximal oxygen uptake (VO2max) in
overweight and obese individuals. In addition, we examined possible concomitant
adaptations in endurance exercise performance (time to exhaustion (TTE)), citrate
synthase (CS) activity, venous and arterial function, blood volume, and
calculated stroke volume (SV). METHODS: Thirty subjects were recruited (age, 41
+/- 9 yr; weight, 91 +/- 14 kg; height, 173 +/- 8 cm; body mass index, 30 +/- 4
kg.m(-2)) and randomized to either 6 wk of 4 * 4-min high-intensity interval
training (4HIIT) at 85%-95% of HRmax, 10 * 1-min HIIT (1HIIT) at VO2max load, or
45-min moderate-intensity continuous training (MICT) at 70% of HRmax. VO2max,
TTE, CS activity, venous and arterial function, as well as blood volume were
measured before and after the training period. O2 pulse was calculated and used
to estimate SV. Analysis was conducted per protocol. RESULTS: Only 4HIIT
increased VO2max (P < 0.01) and significantly more compared with 1HIIT (P = 0.04)
and MICT (P = 0.03) (4HIIT, 10%; 1HIIT, 3.3%; and MICT, 3.1%). All groups
increased TTE (4HIIT, 198%; 1HIIT, 116%; MICT, 52%), with a higher increase after
4HIIT compared with that after MICT (P = 0.02). Calculated SV increased only
after 4HIIT (14.4%). Plasma volume and hemoglobin mass increased after 1HIIT only
(5.6% and 6.5%); however, no group differences were found. All groups increased
CS activity (4HIIT, 35%; 1HIIT, 35%; MICT, 56%), with no group differences.
Arterial inflow (15.7%) and venous outflow (22.7%) decreased after MICT, but
there were no group differences. CONCLUSIONS: 4HIIT was superior to 1HIIT and
MICT in improving VO2max likely because of an increased SV.
PMID- 26440135
TI - 1,6-Conjugated Addition-Mediated [2+1] Annulation: Approach to Spiro[2.5]octa-4,7
dien-6-one.
AB - A formal 1,6-conjugated addition-mediated [2+1] annulation to synthesize
spiro[2.5]octa-4,7-dien-6-one with p-quinone methides and sulfur ylides has been
described. This domino-type process was highly diastereoselective and exhibited
good functional group tolerance and scalability without the use of metals and
bases.
PMID- 26440136
TI - Peroxidised dietary lipids impair intestinal function and morphology of the small
intestine villi of nursery pigs in a dose-dependent manner.
AB - The objective of this study was to investigate the effect of increasing degrees
of lipid peroxidation on structure and function of the small intestine of nursery
pigs. A total of 216 pigs (mean body weight was 6.5 kg) were randomly allotted
within weight blocks and sex and fed one of five experimental diets for 35 d
(eleven pens per treatment with three to four pigs per pen). Treatments included
a control diet without added lipid, and diets supplemented with 6 % soyabean oil
that was exposed to heat (80 degrees C) and constant oxygen flow (1 litre/min)
for 0, 6, 9 and 12 d. Increasing lipid peroxidation linearly reduced feed intake
(P<0.001) and weight gain (P=0.024). Apparent faecal digestibility of gross
energy (P=0.001) and fat (P<0.001) decreased linearly as the degree of
peroxidation increased. Absorption of mannitol (linear, P=0.097) and d-xylose
(linear, P=0.089), measured in serum 2 h post gavage with a solution containing
0.2 g/ml of d-xylose and 0.3 g/ml of mannitol, tended to decrease progressively
as the peroxidation level increased. Increasing peroxidation also resulted in
increased villi height (linear, P<0.001) and crypt depth (quadratic, P=0.005) in
the jejunum. Increasing peroxidation increased malondialdehyde concentrations
(quadratic, P=0.035) and reduced the total antioxidant capacity (linear, P=0.044)
in the jejunal mucosa. In conclusion, lipid peroxidation progressively diminished
animal performance and modified the function and morphology of the small
intestine of nursery pigs. Detrimental effects were related with the disruption
of redox environment of the intestinal mucosa.
PMID- 26440137
TI - Interleukin 4 inhibition as a potential therapeutic in pemphigus.
AB - Pemphigus is an autoimmune bullous skin disease that results from desmosomal
protein desmoglein 3 and 1 loss in pemphigus vulgaris and foliaceus,
respectively. It can be considered as a Th2-dominant disease over-expressed by
Th2 cell cytokines. Interleukin (IL)-4 is a key cytokine which can exacerbate Th2
over-expression in addition to isotype switching to immunoglobin (Ig)G1 and IgG4
that are responsible for desmoglein loss. Elevation of IL-4 level has also been
reported in various studies. Considering the important role of IL-4 in severe
phase of pemphigus and lack of effective and safeness therapy for this
potentially fatal disease, anti-IL-4 therapy was introduced as a potential
curative for pemphigus disease. This study reviewed all studies about any roles
of IL-4 that can directly and indirectly be played in the development of
pemphigus and IL-4 inhibition with interferons and dupilumab therapy were
introduced as a novel pemphigus treatment for patients who are in relapse phase
of the disease. Dupilumab was also introduced as a possible treatment for
patients with severe pemphigus. It can directly inhibit IL-4 by targeting IL-4
alpha-chain receptor. IL-4 inhibition can lead to the creation of Th1:Th2 balance
by various pathways, discussed in this study.
PMID- 26440138
TI - Emerging roles of the Th17/IL-17-axis in glomerulonephritis.
AB - Different T cell subsets have been implicated in the pathogenesis of
glomerulonephritis. Several lines of evidence indicate the recently identified
interleukin-17 (IL-17)-producing T cells (Th17 cells) to be involved in the renal
inflammatory cascade associated with glomerulonephritis. In this review we
outline different forms of glomerulonephritis and the contribution of the Th17/IL
17-axis in mediating the downstream effects and pathology associated with the
disease. Learning more about the Th17/IL-17-axis can help to develop promising
therapeutic strategy for the treatment of various forms of glomerulonephritis.
PMID- 26440139
TI - Psychometric evaluation of the adolescent and parent versions of the Gaming
Addiction Identification Test (GAIT).
AB - The objective of the study is to evaluate the psychometric properties of the
Gaming Addiction Identification Test (GAIT) and its parent version (GAIT-P), in a
representative community sample of adolescents and parents in Vastmanland,
Sweden. Self-rated and parent-rated gaming addictive symptoms identified by GAIT
and GAIT-P were analyzed for frequency of endorsement, internal consistency,
concordance, factor structure, prevalence of Internet gaming disorder (IGD),
concurrence with the Gaming Addiction Scale for Adolescents, 7-item version (GAS)
and the parent version of GAS (GAS-P), and for sex differences. The 12-month
prevalence of IGD was found to be 1.3% with GAIT and 2.4% with GAIT-P. Results
also indicate promising psychometric results within this population, with high
internal consistency, and high concurrent validity with GAS and GAS-P.
Concordance between adolescents and parents ratings was high, although moderate
in girls. Although exploratory factor analysis indicated poor model fit, it also
indicated unidimensionality and high factor loadings in all analyses. GAIT and
GAIT-P are suitable for continued use in measuring gaming addiction in
adolescents, and, with the additional two items, they now cover all nine IGD
criteria.
PMID- 26440140
TI - Synthesis of Upconverting Hydrogel Nanocomposites Using Thiol-Ene Click
Chemistry: Template for the Formation of Dendrimer-Like Gold Nanoparticle
Assemblies.
AB - The synthesis of upconverting hydrogel nanocomposites by base-catalyzed thiol-ene
click reaction between 10-undecenoic acid capped Yb(3+)/Er(3+)-doped NaYF4
nanoparticles and pentaerythritol tetrakis(3-mercaptopropionate) (PETMP) as
tetrathiol monomer is reported. This synthetic strategy for nanocomposite gels is
quite different from works where usually the preformed gels are mixed with the
nanoparticles. Developing nanocomposites by surface modification of capping
ligands would allow tuning and controlling of the separation of the nanoparticles
inside the gel network. The hydrogel nanocomposites prepared by thiol-ene click
reaction show strong enhancement in luminescence intensity compared to 10
undecenoic acid-capped Yb(3+)/Er(3+)-doped NaYF4 nanoparticles through the
upconversion process (under 980 nm laser excitation). The hydrogel nanocomposites
display strong swelling characteristics in water resulting in porous structures.
Interestingly, the resulting nanocomposite gels act as templates for the
synthesis of dendrimer-like Au nanostructures when HAuCl4 is reduced in the
presence of the nanocomposite gels.
PMID- 26440141
TI - Unique Electronic and Structural Effects in Vanadia/Ceria-Catalyzed Reactions.
AB - Vanadia/ceria supported catalysts exhibit ultrahigh catalytic activities in
oxidative dehydrogenation (ODH) reactions. Here, we performed systematic density
functional theory calculations to illustrate the underlying mechanisms. It is
found that unique electronic and structural effects are both crucial in the
catalytic processes. Calculations of the catalytic performance of different
oxygen species in oxidation of methanol to formaldehyde suggested that the oxygen
of the interface V-O-Ce group is catalytically more active, especially when H
adsorption energy is small, indicating the strong structural effect in the
vanadia/ceria supported catalyst. In addition, new empty localized states of O 2p
generated in a ceria-supported system through depositing VO3- and VO4-type
monomeric vanadia species are determined to participate in the whole ODH reaction
processes and help to reduce the barriers at various steps.
PMID- 26440142
TI - The neuropeptide SIFamide in the brain of three cockroach species.
AB - The sequence as well as the distribution pattern of SIFamide in the brain of
different insects is highly conserved. As a general rule, at least four prominent
SIFamide-immunoreactive somata occur in the pars intercerebralis. They arborize
throughout the brain and the ventral nerve cord. Whereas SIFamide is implicated
in mating and sleep regulation in Drosophila, other functions of this peptide
remain largely unknown. To determine whether SIFamide plays a role in the
circadian system of cockroaches, we studied SIFamide in Rhyparobia (= Leucophaea)
maderae (Blaberidae), Periplaneta americana (Blattidae), and Therea petiveriana
(Polyphagidae). Matrix-assisted laser desorption/ionization-time of flight (MALDI
TOF) mass spectrometry revealed identical SIFamide sequences (TYRKPPFNGSIFamide)
in the three species. In addition to four large immunoreactive cells in the pars
intercerebralis (group 1), smaller SIFamide-immunoreactive somata were detected
in the pars intercerebralis (group 2), in the superior median protocerebrum
(group 3), and in the lateral protocerebrum (group 4). Additional cells in the
optic lobe (group 5) and posterior protocerebrum (group 6) were stained only in
P. americana. Almost the entire protocerebrum was filled with a beaded network of
SIFamide-immunoreactive processes that especially strongly invaded the upper unit
of the central body. Double-label experiments did not confirm colocalizations
with gamma-aminobutyric acid (GABA) or the circadian coupling peptide pigment
dispersing factor (PDF). In contrast to locusts, colocalization of SIFamide and
histamine immunoreactivity occurred not in group 1, but in group 4 cells. Because
the accessory medulla displayed SIFamide immunoreactivity and injections of
SIFamide delayed locomotor activity rhythms circadian time-dependently, SIFamide
plays a role in the circadian system of cockroaches. J. Comp. Neurol. 524:1337
1360, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26440143
TI - Editorial Comment.
PMID- 26440145
TI - Chinese version of the Schizotypal Personality Questionnaire: Factor structure
replication and invariance across sex.
AB - INTRODUCTION: The Schizotypal Personality Questionnaire (SPQ) is a self-report
measure assessing symptoms of schizotypy. The SPQ has been used in both normative
and clinical samples and has much theoretical and empirical support. A three
factor structure of the SPQ, derived on the basis of work in schizophrenia,
consisting of Cognitive-Perceptual, Interpersonal, and Disorganized factors, has
been well replicated. The present study aimed to (i) validate this three-factor
structure in the Chinese version of the SPQ in a sample of individuals of Chinese
ethnicity, and (ii) test for invariance across sex. METHODS: A total of 209 (99
males) undergraduate university students (Mage = 19.5, SD = 1.6) were
administered the SPQ. RESULTS: Confirmatory factor analysis indicated a better
fit between the data and the three-factor model compared with a one-factor model.
Multigroup confirmatory factor analysis also found strong measurement invariance
across sex. DISCUSSION: The current results add to a growing body of literature
evidencing cross-cultural validity of the SPQ and its invariance across sex.
Research and clinical implications of the current results are discussed.
PMID- 26440146
TI - Environmental chemicals active as human antiandrogens do not activate a
stickleback androgen receptor but enhance a feminising effect of oestrogen in
roach.
AB - Sexual disruption is reported in wild fish populations living in freshwaters
receiving discharges of wastewater treatment works (WwTW) effluents and is
associated primarily with the feminisation of males by exposure to oestrogenic
chemicals. Antiandrogens could also contribute to the feminisation of male fish,
but there are far less data supporting this hypothesis and almost nothing is
known for the effects of oestrogens in combination with antiandrogens in fish. We
conducted a series of in vivo exposures in two fish species to investigate the
potency on reproductive-relevant endpoints of the antiandrogenic antimicrobials
triclosan (TCS), chlorophene (CP) and dichlorophene (DCP) and the resin, abietic
acid (AbA), all found widely in WwTW effluents. We also undertook exposures with
a mixture of antiandrogens and a mixture of antiandrogens in combination with the
oestrogen 17alpha-ethinyloestradiol (EE2). In stickleback (Gasterosteus
aculeatus), DCP showed a tendency to reduce spiggin induction in females
androgenised by dihydrotestosterone (DHT), but these findings were not
conclusive. In roach (Rutilus rutilus), exposures to DCP (178 days), or a mixture
of TCS, CP and AbA (185 days), or to the model antiandrogen flutamide (FL, 178
days) had no effect on gonadal sex ratio or on the development of the
reproductive ducts. Exposure to EE2 (1.5ng/L, 185 days) induced feminisation of
the ducts in 17% of the males and in the mixture of antiandrogens (TCS, CP, AbA)
in combination with EE2, almost all (96%) of the males had a feminised
reproductive ducts. In stickleback androgen receptor (ARalpha and ARbeta)
transactivation assays, the model antiandrogens, FL and procymidone inhibited 11
ketotestosterone (11-KT) induced receptor activation, but none of the human
antiandrogens, TCS, CP, DCP and AbA had an effect. These data indicate that
antimicrobial antiandrogens in combination can contribute to the feminisation
process in exposed males, but they do not appear to act through the androgen
receptor in fish.
PMID- 26440147
TI - Epigenetic silencing of miR-145-5p contributes to brain metastasis.
AB - Brain metastasis is a major cause of morbidity and mortality of lung cancer
patients. We assessed whether aberrant expression of specific microRNAs could
contribute to brain metastasis. Comparison of primary lung tumors and their
matched metastatic brain disseminations identified shared patterns of several
microRNAs, including common down-regulation of miR-145-5p. Down-regulation was
attributed to methylation of miR-145's promoter and affiliated elevation of
several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly,
tumor protein D52 (TPD52). In line with these observations, restored expression
of miR-145-5p and selective depletion of individual targets markedly reduced in
vitro and in vivo cancer cell migration. In aggregate, our results attribute to
miR-145-5p and its direct targets pivotal roles in malignancy progression and in
metastasis.
PMID- 26440148
TI - The timing of surgery after neoadjuvant radiotherapy influences tumor
dissemination in a preclinical model.
AB - Neoadjuvant radiotherapy (neoRT) used in cancer treatments aims at improving
local tumor control and patient overall survival. The neoRT schedule and the
timing of the surgical treatment (ST) are empirically based and influenced by the
clinician's experience. The current study examines how the sequencing of neoRT
and ST affects metastatic dissemination. In a breast carcinoma model, tumors were
exposed to different neoRT schedules (2x5Gy or 5x2Gy) followed by surgery at day
4 or 11 post-RT. The impact on the tumor microenvironment and lung metastases was
evaluated through immunohistochemical and flow cytometry analyses. After 2x5Gy,
early ST (at day 4 post-RT) led to increased size and number of lung metastases
as compared to ST performed at day 11. Inversely, after 5x2Gy neoRT, early ST
protected the mice against lung metastases. This intriguing relationship between
tumor aggressiveness and ST timing could not be explained by differences in
classical parameters studied such as hypoxia, vessel density and matrix
remodeling. The study of tumor-related inflammation and immunity reveals an
increased circulating NK cell percentage following neoRT as compared to non
irradiated mice. Then, radiation treatment and surgery were applied to tumor
bearing NOD/SCID mice. In the absence of NK cells, neoRT appears to increase lung
metastatic dissemination as compared to non irradiated tumor-bearing mice.
Altogether our data demonstrate that the neoRT schedule and the ST timing affect
metastasis formation in a pre-clinical model and points out the potential role of
NK cells. These findings highlight the importance to cautiously tailor the
optimal window for ST following RT.
PMID- 26440149
TI - Lack of intracellular replication of M. tuberculosis and M. bovis BCG caused by
delivering bacilli to lysosomes in murine brain microvascular endothelial cells.
AB - Invasion and traversal of the blood-brain barrier (BBB) by Mycobacterium
tuberculosis cause meningeal tuberculosis (TB) in the central nervous system
(CNS). Meningeal TB is a serious, often fatal disease that disproportionately
affects young children. The mechanisms involved in CNS invasion by M.
tuberculosis bacilli are poorly understood. In this study, we microscopically
examined endosomal trafficking and measured survival of M. tuberculosis and M.
bovis Bacille Calmette-Guerin (BCG) bacilli in murine brain microvascular
endothelial cells (BMECs). The results show that both species internalize but do
not replicate in BMECs in the absence of a cytotoxic response. Confocal
microscopy indicates that bacilli-containing vacuoles are associated with the
early endosomal marker, Rab5, late endosomal marker, Rab7, and lysosomal marker,
LAMP2, suggesting that bacilli-containing endosomes mature into endolysosomes in
BMECs. Our data also show that a subset of intracellular M. tuberculosis, but not
BCG bacilli, escape into the cytoplasm to avoid rapid lysosomal killing. However,
the intracellular mycobacteria examined cannot spread cell-to-cell in BMECs.
Taken together, these data show that with the exception of the small terminal
cytoplasmic population of bacilli, M. tuberculosis does not modulate
intracellular trafficking in BMECs as occurs in macrophages and lung epithelial
and endothelial cells.
PMID- 26440150
TI - Fendiline inhibits proliferation and invasion of pancreatic cancer cells by
interfering with ADAM10 activation and beta-catenin signaling.
AB - ADAM10 (A Disintegrin and Metalloprotease Domain 10) affects the pathophysiology
of various cancers, and we had shown that inhibition of ADAM10 sensitizes
pancreatic cancer cells to gemcitabine. ADAM10 is activated in response to
calcium influx, and here we examined if calcium channel blockers (CCB) would
impede ADAM10 activation and affect biology of pancreatic cancer cells. We find
that the CCB, fendiline, significantly reduces proliferation, migration,
invasion, and anchorage independent growth of pancreatic cancer cells. This was
associated with ADAM10 inhibition and its localization at the actin-rich membrane
protrusions. Further, fendiline-treated cells formed cadherin-catenin positive
tight adherens junctions and elicited defective protein trafficking and
recycling. Furthermore, the expression of beta-catenin target genes, cyclinD1, c
Myc and CD44, were significantly decreased, suggesting that fendiline might
prevent cell proliferation and migration by inhibiting ADAM10 function, cadherin
proteolysis and stabilization of cadherin-catenin interaction at the plasma
membrane. This will subsequently diminish beta-catenin intracellular signaling
and repress TCF/LEF target gene expression. Supporting this notion, RNAi-directed
downregulation of ADAM10 in cancer cells decreased the expression of cyclinD1, c
Myc and CD44. Furthermore, analysis of human pancreatic tumor tissue microarrays
and lysates showed elevated levels of ADAM10, suggesting that aberrant activation
of ADAM10 plays a fundamental role in growth and metastasis of PDACs and
inhibiting this pathway might be a viable strategy to combat PDACs.
PMID- 26440151
TI - Dietary NiCl2 causes G2/M cell cycle arrest in the broiler's kidney.
AB - Here we showed that dietary NiCl2 in excess of 300 mg/kg caused the G2/M cell
cycle arrest and the reduction of cell proportion at S phase. The G2/M cell cycle
arrest was accompanied by up-regulation of phosphorylated ataxia telangiectasia
mutated (p-ATM), p53, p-Chk1, p-Chk2, p21 protein expression and ATM, p53, p21,
Chk1, Chk2 mRNA expression, and down-regulation of p-cdc25C, cdc2, cyclinB and
proliferating cell nuclear antigen (PCNA) protein expression and the cdc25, cdc2,
cyclinB, PCNA mRNA expression.
PMID- 26440152
TI - Human anterior thalamic nuclei are involved in emotion-attention interaction.
AB - Patients treated with deep brain stimulation (DBS) provide an opportunity to
study affective processes in humans with "lesion on demand" at key nodes in the
limbic circuitries, such as at the anterior thalamic nuclei (ANT). ANT has been
suggested to play a role in emotional control with its connection to the
orbitofrontal cortex and the anterior cingulate cortex. However, direct evidence
for its role in emotional function in human subjects is lacking. Reported side
effects of ANT-DBS in the treatment of refractory epilepsy include depression
related symptoms. In line with these mood-related clinical side effects, we have
previously reported that stimulating the anterior thalamus increased emotional
interference in a visual attention task as indicated by prolonged reaction times
due to threat-related emotional distractors. We used event-related potentials to
investigate potential attentional mechanism behind this behavioural observation.
We hypothesized that ANT-DBS leads to greater attention capture by threat-related
distractors. We tested this hypothesis using centro-parietal N2-P3 peak-to-peak
amplitude as a measure of allocated attentional resources. Six epileptic patients
treated with deep brain stimulation at ANT participated in the study.
Electroencephalography was recorded while the patients performed a computer based
Executive-Reaction Time test with threat-related emotional distractors. During
the task, either ANT or a thalamic control location was stimulated, or the
stimulation was turned off. Stimulation of ANT was associated with increased
centro-parietal N2-P3 amplitude and increased reaction time in the context of
threat-related emotional distractors. We conclude that high frequency electric
stimulation of ANT leads to greater attentional capture by emotional stimuli.
This is the first study to provide direct evidence from human subjects with on
line electric manipulation of ANT for its role in emotion-attention interaction.
PMID- 26440154
TI - Technical note: Production of tetraploid sturgeons.
AB - Studies and practical application of androgenesis and gynogenesis in sturgeon are
significantly hindered by strong influence of ploidy restoration treatment on
survivability of progeny; therefore, developed method of production of tetraploid
broodstock and, consequently, use of their diploid gametes might help to avoid
ploidy restoration treatment. In the present study, for the first time was
developed a protocol for tetraploidy induction in 2 model sturgeon species,
sterlet () and Siberian sturgeon (). A high efficiency of treatment was achieved
by optimization of heat shock using a temperature of 37 degrees C for 2 min timed
between the end of female pronuclei formation and the beginning of pronuclei
migration, that is, 0.8 to 1.0 tau (duration of 1 mitotic cycle during the period
of synchronous cleavage division). Fertilized eggs developed in tetraploid
larvae, up to 31 (89.6% in control) and 34% (70.9% in control) in sterlet and
Siberian sturgeon, respectively. Most of the tetraploid larvae exhibited body
malformations; as a result, consequent large scale study revealed high larval
mortality, which drastically decreased after 2 mo of age. Consequent comparison
of BW, length, and malformation rate and mortality between diploid and tetraploid
progeny of sterlet did not reveal significant differences in fitness of diploid
and tetraploid juveniles at 9 and 11 mo of age. The present study can be
considered the first step towards improving the androgenesis methods of
conservation of endangered sturgeons as well as understanding the sturgeon sex
determination system through induction of mitotic gynogenesis.
PMID- 26440153
TI - Genetic relationships between measures of sexual development, boar taint, health,
and aggressiveness in pigs.
AB - Breeding intact boars is a promising alternative to surgical castration of
piglets. Genetic selection should enable farmers to solve problems due to boar
taint and aggressiveness while taking into account potential consequences on
other traits of interest. The aim of the study was to estimate genetic relations
between sexual development, boar taint, health, and aggressiveness. About 1,600
Pietrain (purebred) or Pietrain * Large White (crossbred) boars were raised in a
testing station. Blood samples were collected at about 105 kg BW for measuring
sex hormones (testosterone and estradiol) and indicators of the inflammatory
status (C-reactive protein [CRP], pig major acute-phase protein [pigMAP], and
blood formula). Animals were slaughtered 9 d later and measured for boar taint
compounds present in fat (androstenone and skatole) and skin lesions on carcass,
an indicator of aggressiveness. For both genetic types, heritability was moderate
for sex hormones (from 0.17 to 0.29) and skatole (0.24 for purebred and 0.37 for
crossbred) and high for androstenone (0.63 and 0.70 for purebred and crossbred,
respectively). Genetic correlations between sex hormones and boar taint compounds
were moderate to high (from 0.31 to 0.95). Heritability was moderate for CRP
(0.24 and 0.46 for purebred and crossbred, respectively) and very low for pigMAP
(0.06 and 0.05 for purebred and crossbred, respectively. Numbers of leukocytes
had moderate to high heritabilities according to the genetic type (from 0.21 to
0.52). Heritability of skin lesions was moderate for both genetic types (0.31).
Genetic correlations were negative between sex hormones and inflammatory measures
(from -0.46 to -0.05), positive between testosterone and number of lesions (0.43
and 0.53 for purebred and crossbred, respectively), and low between androstenone
and lesions (-0.06 and -0.17 for purebred and crossbred, respectively). Overall,
both breeds of pigs had very similar estimations of heritabilities, but estimates
of genetic correlations were different for some pairs of traits. It would be
possible to select boars based on their plasma concentration of sex hormones to
decrease boar taint and aggressiveness without important consequences on the
immune response. However, because of the strong links between boar taint and
reproductive function, the possible consequences on the reproductive performance
should be evaluated.
PMID- 26440155
TI - Derivation of a new lamb survival trait for the New Zealand sheep industry.
AB - Previous research identified that a review of the current industry New Zealand
lamb survival trait was necessary as its recording accuracy was reliant on
farmers notifying their Sheep Improvement Limited bureau of lamb deaths. This
paper reports the decision rules and genetic parameters for a new lamb survival
trait for the New Zealand sheep industry. These rules define the new lamb
survival trait (NEWSUR) using lamb birth fate (BFATE) codes and the
presence/absence of lamb weight measurements. Six univariate animal models were
tested and used to estimate variance or covariance components and the resulting
direct and maternal heritabilities for NEWSUR. The models differed in the way
they adjust for the effect of day of birth, the exclusion or inclusion of a
litter (dam/year of birth) random effect, and the application or not of a logit
transformation of the phenotypes. For both the linear and logistic methods,
models including the random effect of litter provided the best fit for NEWSUR
according to log-likelihood values. Log-likelihoods for the linear and logistic
models cannot be compared; therefore, a cross-validation method was used to
assess whether the logit transformation was appropriate by analyzing the
predictive ability of the models. The mean square errors were slightly lower for
the linear compared with the logistic model, and therefore, the linear model was
recommended for industry use. The heritability attributed to direct effects
ranged from 2 to 5.5%. A direct heritability of 5.5% resulted from a linear model
without litter effect and omitting the effect of day of birth on survival,
whereas a direct heritability of 2% resulted from the logistic model fitting a
random litter effect. The heritability attributed to maternal genetic effects
ranged from 1.9 to 7.7%. A maternal genetic heritability of 7.7% resulted from
the logistic model omitting the litter effect, whereas a maternal genetic
heritability of 1.9% resulted from the linear model fitting a random litter
effect. The addition of the litter random effect substantially decreased the
maternal heritabilities in all cases and was recommended for industry use to
avoid overestimation of the maternal genetic variance. Sheep Improvement Limited
has implemented NEWSUR and the associated genetic evaluation model based on
information described in this paper. Industry-wide implementation will enable
sheep breeders to produce more accurate genetic evaluations to their commercial
clients.
PMID- 26440156
TI - Population genetic structure in farm and feral American mink (Neovison vison)
inferred from RAD sequencing-generated single nucleotide polymorphisms.
AB - Feral American mink populations (), derived from mink farms, are widespread in
Europe. In this study we investigated genetic diversity and genetic
differentiation between feral and farm mink using a panel of genetic markers (194
SNP) generated from RAD sequencing data. Sampling included a total of 211
individuals from 14 populations, 4 feral and 10 from farms, the latter including
a total of 7 color types (Brown, Black, Mahogany, Sapphire, White, Pearl, and
Silver). Our study revealed similar low levels of genetic diversity in both farm
and feral mink. Results are consistent with small effective population size as a
consequence of line selection in the farms and founder effects of a few escapees
from the farms in feral populations. Moderately high genetic differentiation was
found between farm and feral animals, suggesting a scenario in which wild
populations were founded from farm escapes a few decades ago. Currently, escapes
and gene flow are probably limited. Genetic differentiation was higher among farm
color types than among farms, consistent with line selection using few
individuals to create the lines. Finally, no indications of inbreeding were found
in either farm or feral samples, with significant negative values found in most
farm samples, showing farms are successful in avoiding inbreeding.
PMID- 26440157
TI - Social genetic effects influence reproductive performance of group-housed sows.
AB - Group housing of gestating sows has implications for reproductive performance due
to detrimental interactions between sows within groups. Reproductive records ( =
10,748) were obtained for 8,444 pedigreed nucleus sows housed in a single
facility, formed into 1,827 static groups during gestation. Only data from
complete groups were used to estimate genetic parameters for total born (TB),
number born alive (NBA), and gestation length (GL) and to compare models extended
to account for group effects. Censored data for sows which did not farrow (0.8%
of records) were augmented with biologically meaningful values. Group sizes
ranged from 2 to 10, in pens designed to hold 4, 8, or 10 sows per pen. Sows were
grouped by parity, line, and mating date after d 35 of pregnancy. Heritability
estimates were generally constant across all model alternatives at 0.11 +/- 0.02
for TB and NBA and 0.32 +/- 0.03 for GL. However, models for all traits were
significantly ( < 0.05) improved through inclusion of terms for nongenetic group
and social genetic effects (SGE). Group effects were no longer significant in
models containing both terms. The proportional contributions of SGE () to
phenotypic variances were very low (<=0.002 across traits), but their
contributions to calculated total genetic variance (T) were significant. The
differences between h and T ranged between 3 and 5% under simple models,
increasing to 8 to 14% in models accounting for both covariances between additive
direct (A) and SGE and the effects of varying group size on the magnitude of
estimates for SGE. Estimates of covariance between A and SGE were sensitive to
the modeling of dilution factors for group size. The models of best fit for
litter size traits used a customized dilution based on sows/pen relative to the
maximum sows/pen. The best model supported a reduction in SGE with increased
space per sow, independent of maximum group size, and no significant correlation
between A and SGE. The latter is expected if A and SGE reflect different trait
complexes. It is suggested that the SGE estimated for reproductive traits
represented the expression of an unobserved phenotype, such as sow aggression, of
an individual on its pen mates. Further investigation into the use of competitive
effects models for genetic evaluation of reproductive traits for group-housed
sows could be considered a strategy to improve welfare and performance of group
housed sows.
PMID- 26440158
TI - Genetic variation in efficiency to deposit fat and lean meat in Norwegian
Landrace and Duroc pigs.
AB - Feed costs amount to approximately 70% of the total costs in pork production, and
feed efficiency is, therefore, an important trait for improving pork production
efficiency. Production efficiency is generally improved by selection for high
lean growth rate, reduced backfat, and low feed intake. These traits have given
an effective slaughter pig but may cause problems in piglet production due to
sows with limited body reserves. The aim of the present study was to develop a
measure for feed efficiency that expressed the feed requirements per 1 kg
deposited lean meat and fat, which is not improved by depositing less fat.
Norwegian Landrace ( = 8,161) and Duroc ( = 7,202) boars from Topigs Norsvin's
testing station were computed tomography scanned to determine their deposition of
lean meat and fat. The trait was analyzed in a univariate animal model, where
total feed intake in the test period was the dependent variable and fat and lean
meat were included as random regression cofactors. These cofactors were measures
for fat and lean meat efficiencies of individual boars. Estimation of fraction of
total genetic variance due to lean meat or fat efficiency was calculated by the
ratio between the genetic variance of the random regression cofactor and the
total genetic variance in total feed intake during the test period. Genetic
variance components suggested there was significant genetic variance among
Norwegian Landrace and Duroc boars in efficiency for deposition of lean meat
(0.23 +/- 0.04 and 0.38 +/- 0.06) and fat (0.26 +/- 0.03 and 0.17 +/- 0.03)
during the test period. The fraction of the total genetic variance in feed intake
explained by lean meat deposition was 12% for Norwegian Landrace and 15% for
Duroc. Genetic fractions explained by fat deposition were 20% for Norwegian
Landrace and 10% for Duroc. The results suggested a significant part of the total
genetic variance in feed intake in the test period was explained by fat and lean
meat efficiency. These new efficiency measures may give the breeders
opportunities to select for animals with a genetic potential to deposit lean meat
efficiently and at low feed costs in slaughter pigs rather than selecting for
reduced the feed intake and backfat.
PMID- 26440159
TI - Genetic principal components for reproductive and productive traits in dual
purpose buffaloes in Colombia.
AB - A multitrait model (MC) and 5 reduced-rank models with principal component
structure (components PC, PC, PC, PC, and PC) were compared. The objectives were
to determine the most appropriate model for estimating genetic parameters and to
evaluate the genetic progress of dual-purpose buffaloes in Colombia using that
model. The traits evaluated were weaning weight (WW), yearling weight (W12),
weight at 18 mo of age (W18), weight at 2 yr of age (W24), age at first calving
(AFC), and milk yield at 270 d of first lactation (MY270). Genealogy and
productive information from 34,326 buffaloes born in Colombia between 1997 and
2014 were used. Colombian Association of Buffalo Breeders (ACB) provided the
data. Direct additive genetic and residual random effects were included for all
the traits. In addition, the maternal additive genetic effect and permanent
environmental random effect were included for WW, while a maternal additive
genetic effect was included for W12. The fixed effects were contemporary group
(farm, year, and calving season: January to April, May to August, or September to
December; for all traits) and sex (for WW, W12, W18, and W24). Additionally,
parity was included as a fixed effect for WW and W12. Age at weighing was used as
a covariate for WW, W12, W18, and W24. Genetic progress of all traits was
analyzed using a generalized smooth model (GAM). According to the Akaike
information criteria (AIC), the best model was the one with reduced rank and
first 3 principal components (PC). This model maintained 100% of the original
variance. Genetic parameters estimated with this model were similar to those
estimated by MC, but with smaller standard errors. Heritability for weight
related traits ranged between 0.23 and 0.44. Heritabilities for AFC and MY270
were 0.14 and 0.24, respectively. The genetic correlations obtained between all
weights (WW, W12, W18, and W24) were positive and high. Correlations between all
weights with AFC were negative and moderate. Correlations between all weights
with MY270 were positive and moderate, and between MY270 with AFC were negative
and low.
PMID- 26440160
TI - Relationships among and variation within rare breeds of swine.
AB - Extinction of rare breeds of livestock threatens to reduce the total genetic
variation available for selection in the face of the changing environment and new
diseases. Swine breeds facing extinction typically share characteristics such as
small size, slow growth rate, and high fat percentage, which limit them from
contributing to commercial production. Compounding the risk of loss of variation
is the lack of pedigree information for many rare breeds due to inadequate herd
books, which increases the chance that producers are breeding closely related
individuals. By making genetic data available, producers can make more educated
breeding decisions to preserve genetic diversity in future generations, and
conservation organizations can prioritize investments in breed preservation. The
objective of this study was to characterize genetic variation within and among
breeds of swine and prioritize heritage breeds for preservation. Genotypes from
the Illumina PorcineSNP60 BeadChip (GeneSeek, Lincoln, NE) were obtained for
Guinea, Ossabaw Island, Red Wattle, American Saddleback, Mulefoot, British
Saddleback, Duroc, Landrace, Large White, Pietrain, and Tamworth pigs. A whole
genome analysis toolset was used to construct a genomic relationship matrix and
to calculate inbreeding coefficients for the animals within each breed.
Relatedness and average inbreeding coefficient differed among breeds, and pigs
from rare breeds were generally more closely related and more inbred ( < 0.05). A
multidimensional scaling diagram was constructed based on the SNP genotypes.
Animals within breeds clustered tightly together except for 2 Guinea pigs.
Tamworth, Duroc, and Mulefoot tended to not cluster with the other 7 breeds.
PMID- 26440161
TI - Estimates of genetic parameters for growth traits in Brahman cattle using random
regression and multitrait models.
AB - Random regression models (RRM) and multitrait models (MTM) were used to estimate
genetic parameters for growth traits in Brazilian Brahman cattle and to compare
the estimated breeding values obtained by these 2 methodologies. For RRM, 78,641
weight records taken between 60 and 550 d of age from 16,204 cattle were
analyzed, and for MTM, the analysis consisted of 17,385 weight records taken at
the same ages from 12,925 cattle. All models included the fixed effects of
contemporary group and the additive genetic, maternal genetic, and animal
permanent environmental effects and the quadratic effect of age at calving (AAC)
as covariate. For RRM, the AAC was nested in the animal's age class. The best RRM
considered cubic polynomials and the residual variance heterogeneity (5 levels).
For MTM, the weights were adjusted for standard ages. For RRM, additive
heritability estimates ranged from 0.42 to 0.75, and for MTM, the estimates
ranged from 0.44 to 0.72 for both models at 60, 120, 205, 365, and 550 d of age.
The maximum maternal heritability estimate (0.08) was at 140 d for RRM, but for
MTM, it was highest at weaning (0.09). The magnitude of the genetic correlations
was generally from moderate to high. The RRM adequately modeled changes in
variance or covariance with age, and provided there was sufficient number of
samples, increased accuracy in the estimation of the genetic parameters can be
expected. Correlation of bull classifications were different in both methods and
at all the ages evaluated, especially at high selection intensities, which could
affect the response to selection.
PMID- 26440162
TI - Effect of resveratrol and lipoic acid on sirtuin-regulated expression of
metabolic genes in bovine liver and muscle slice cultures.
AB - Sirtuins (Sirt) are NAD-dependent deacetylases that are activated by the
antioxidants resveratrol (RSV) and lipoic acid (LA). The objective of this study
was to determine in bovine liver and muscle slice cultures the effect of RSV and
LA treatment on the expresssion of Sirt1, Sirt3, peroxisome proliferator
activated receptor gamma coactivator 1alpha (PPARGC1A), and the forkhead box O
transcription factors FoxO1 and FoxO3 as well as other factors involved in
glucose and lipid metabolism and related to Sirt activity. Tissue slices from
crossbred bulls were treated during 60 min with 40 or 80 MU RSV and 30, 100, 300,
or 1,000 MU LA under restricted conditions (Krebs-Ringer buffer without
nutrients) and fed conditions (2.5 m propionate in combination with 1 n glucagon)
for liver slices or with 0.01 MU epinephrine for muscle slices. Quantitative real
time PCR was used to analyze the expression of the mRNA for the genes studied and
western blot analysis for the expression of the protein for Sirt1. Our results
show that the expression of the mRNA for Sirt1 was enhanced by RSV in liver under
restriction ( <= 0.0112) and by LA in muscle, more under restriction ( <= 0.0121)
than after epinephrine administration ( < 0.0001). Sirt3 is affected in a dose
dependent manner by both compounds in both tissues and under both metabolic
conditions ( <= 0.0452). The expression of the protein for Sirt1 was increased by
LA in both tissues under restricted conditions ( = 0.0026 and = 0.0201,
respectively) but in liver also in fed conditions ( = 0.0016). Genes involved in
the antioxidant response were upregulated in both tissues. These results indicate
that bovine Sirt respond differently to RSV and LA stimulation than monogastric
Sirt do and that gluconeogenesis in ruminants is not related to Sirt to the same
degree as in monogastric species. However, these results provide information
about the possible role of Sirt in ruminant metabolism.
PMID- 26440163
TI - Heat stress enhances adipogenic differentiation of subcutaneous fat depot-derived
porcine stromovascular cells.
AB - Heat stress (HS) results from excessive heat load on animals such that all
adaptive mechanisms used to dissipate the heat do not return the body to normal
body temperature. In pigs, HS results in increased fat deposition compared with
pair-fed animals in a thermoneutral environment. Although there is evidence that
HS increases activity of lipoprotein lipase (LPL) in adipose tissue of heat
stressed pigs, the fundamental causes of the increased adiposity are still
unknown. It remains unclear whether HS directly alters metabolism in adipocytes.
Therefore, to understand the mechanism of HS effects on porcine adipocytes, we
used an in vitro adipocyte differentiation model to characterize cellular
responses that occur during differentiation of pig adipocytes. Preadipocytes
(stromovascular cells) were differentiated for 9 d at a normal (37 degrees C) or
HS (41.5 degrees C) temperature under 5% CO. Expressions of HS genes such as heat
shock proteins (HSP; HSP27, HSP60, HSP70, and HSP90), adipogenic markers
peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT/enhancer
binding proteins alpha (C/EBPalpha), fatty acid synthase (FAS), adipocyte protein
2 (aP2), fatty acid translocase 36 (CD36), fatty acid transport protein 4
(FATP4), fatty acid transport protein 6 (FATP6), LPL, glucose transporter protein
type 4 (GLUT4), phosphoenolpyruvate carboxykinase 1 (PCK1 or PEPCK-C), and
glycerol kinase (GK) and adipokines (adiponectin and leptin) were determined by
real-time-PCR and immunoblotting or ELISA. Cellular triglyceride (TAG) and ATP
concentrations were also determined. As expected, HS increased ( < 0.05) the
expressions of HSP genes. There was no HS treatment effect on the level of
PPARgamma, although C/EBPalpha was induced ( < 0.05) in HS. So it remains unclear
whether HS affects adipocyte differentiation. However, HS leads to increased
expressions of genes involved in fatty acid uptake and TAG synthesis (FAS, aP2,
CD36, FATP4, FATP6, LPL, GLUT4, PCK1, and GK). This is supported by increased
cellular TAG under HS. Therefore, HS promotes increased adipocyte TAG storage,
perhaps through upregulation of genes involved in fatty acid uptake and TAG
synthesis.
PMID- 26440164
TI - The effect of the inclusion of recycled poultry bedding and the physical form of
diet on the performance, ruminal fermentation, and plasma metabolites of
fattening lambs.
AB - During a 125-d experimental period, 24 Afshari * Kurdish male lambs initially
weighing 25.2 +/- 1.2 kg were grouped by BW and randomly assigned to treatments
under a completely randomized design with a 2 * 2 factorial arrangement of
treatments to evaluate the effects of feeding recycled poultry bedding (RPB; 0
and 200 g/kg DM) and the physical form of the diet (mash and block) on nutrient
intake and digestibility, ruminal and plasma parameters, microbial N supply, N
balance, feeding behavior, and growth performance of the lambs. Two diets with
and without RPB in both mash and block form were prepared. Neither the inclusion
of RPB nor the physical form of the diet affected the concentration of VFA or the
total tract apparent digestibility of nutrients. Dietary RPB inclusion increased
DMI ( < 0.01), tended ( = 0.10) to reduce ADG, and decreased G:F ( = 0.05). The
physical form of the diet had no effect on DMI but decreased ADG ( = 0.01) and
G:F ( = 0.02) in lambs fed on the block diet compared with those fed on the mash
diet. Neither the inclusion of RPB nor the physical form of the diets had any
effect on microbial N supply (g/d) and N retention. Rate of eating ( = 0.07),
time spent eating ( = 0.87) and ruminating ( = 0.28), and total chewing activity
( = 0.65) were not affected by dietary RPB inclusion. Rate of eating decreased (
< 0.01) and time spent eating and total chewing activity increased ( = 0.01 and =
0.02, respectively) in lambs fed on the block diet compared with those fed on the
mash diet. Results of the current study showed that inclusion of RPB up to 200
g/kg DM in diets for fattening was possible without any effect on performance and
animal health. Processing of feed into the mash form gave higher livestock
productivity in comparison to the block form.
PMID- 26440165
TI - Mean pulmonary arterial pressures in Angus steers increase from cow-calf to
feedlot-finishing phases.
AB - Pulmonary arterial hypertension due to hypoxia-induced pulmonary vascular
remodeling is the predominant cause of right-sided congestive heart failure (CHF)
in cattle. Historically, heart failure was problematic only at altitudes over
2,134 m. However, anecdotal reports suggest that the incidence of heart failure
is increasing in feedlot cattle at moderate altitude (800 to 1,600 m), with late
fed, or fat, cattle at greatest risk. The goal of this study was to evaluate
pulmonary arterial pressures (PAP) in a cohort of male Angus calves from suckling
to finishing to better understand why heart failure is particularly problematic
in fat cattle. It was hypothesized that mean PAP would increase through the
feeding period and that the calves with the greatest pressures at high altitude
would have the greatest pressures as fat cattle. A total of 362 PAP measurements
were obtained from 153 calves. Calves were tested at altitudes of 2,170 (4 and 6
mo old), 1,560 (13 mo old), and 1,300 m (13 and 18 mo old). Mean PAP were greater
in 18-mo-old steers than any other age group (mean = 50.3 mm Hg; 95% confidence
interval 48.2 to 52.4; < 0.05). Calves that had the greatest mean pressure at 6
mo of age tended to have the greatest mean pressures at 18 mo of age ( = 0.45, <
0.001). The increase in mean PAP with increasing age and adiposity likely
predisposed the steers to an increased risk of CHF during the finishing phase.
PMID- 26440166
TI - A comparison of the physiological response to tolt and trot in the Icelandic
horse.
AB - This study compared the effect of ridden tolt and trot at 3 speeds on
physiological responses in trained adult (15.3 +/- 1.6 yr) Icelandic horses. The
experiment had a crossover design with 8 horses, 2 treatments (incremental
exercise test in tolt and trot), and 2 riders. Each horse performed 2 tests per
day (1 gait with 2 riders, minimum 4.5 h between) on 2 separate days, with 1 d of
rest in between. The exercise test consisted of three 642-m phases at 3.0 m/s
(Speed), 4.0 m/s (Speed), and 5.0 m/s (Speed) and was performed outdoors on a 300
m oval gravel riding track in northern Iceland in May 2012. Heart rate (HR) was
measured during warm-up, the exercise test, and after 5, 15, and 30 min of
recovery. Blood samples were taken at rest, after warm-up, after each phase of
the exercise test, and after 5, 15, and 30 min of recovery. Respiratory rate was
counted for at least 15 s at rest, at the end of the exercise test, and at the
end of the 30-min recovery, and rectal temperature was measured on these
occasions. There were no differences in HR between tolt and trot at any time
point ( > 0.05). At Speed, hematocrit and plasma lactate concentration were
greater ( < 0.05) in tolt (40% +/- 1%, 1.1 +/- 0.06 mmol/L) than in trot (39% +/-
1%; 0.9 +/- 0.06 mmol/L). There was a prolonged recovery of hematocrit and
respiratory rate, a slower decrease in rectal temperature, and a tendency of a
prolonged recovery of plasma lactate concentration ( = 0.0675) after tolt. In
conclusion, there were only minor differences in physiological responses to tolt
and trot in this selected group of experienced adult Icelandic horses and the
biological and practical significance of the slightly elevated physiological
responses to tolt and the slower recovery remains to be determined.
PMID- 26440167
TI - Metabolic, endocrine, and reproductive responses of beef heifers submitted to
different growth strategies during the lactation and rearing periods.
AB - The effects of different feeding strategies (0.7 kg/d target ADG [LO] and 1.0
kg/d target ADG [HI] during the lactation period (LACT; 0-6 mo) and the rearing
period (REAR; 6-15 mo; HI-HI, HI-LO, LO-HI, and LO-LO treatments) on the growth
and reproductive parameters of beef heifers bred by fixed-time AI at 15 mo were
analyzed. Animal weights were recorded weekly (from birth to 18 mo), and size
measures were recorded at 6 and 15 mo. Heifers were bled to determine the onset
of puberty and the metabolic and endocrine (IGF-I and leptin) status. During
lactation, calves in the high lactation treatment (LactHI) had greater weight ( <
0.001), weight gain ( < 0.001), and body size ( < 0.001) than calves in the low
lactation treatment (LactLO). The greater energy balance of LactHI heifers at
weaning was reflected in greater concentrations of plasma glucose ( < 0.001),
urea ( < 0.001), and IGF-I ( < 0.001); plasma levels of NEFA were lower ( <
0.001). During REAR, LactLO heifers had a greater growth rate than did LactHI
heifers ( < 0.001), partially overcoming the lower gains during lactation. The
differences in size measurements registered at weaning were also compensated,
with the exception of LO-LO heifers. The IGF-I profile was highly correlated with
animal performance traits and metabolic profiles, providing a useful indicator of
growth, nutritional, and metabolic status at key points in development. By
contrast, the function of leptin as an indicator of growth and reproductive
development of heifers was less clear. All treatments had similar weights at
puberty onset (55.9% mature BW), although LactLO ( < 0.01) and the low rearing
treatment (RearLO; < 0.001) heifers were older than the others. The animals with
greater glucose and IGF-I levels at weaning and greater cholesterol
concentrations during REAR reached puberty earlier. The fertility rate (86%) was
similar among treatments. The heifers in the high rearing treatment (RearHI)
required more AI services to become pregnant and were older at conception ( <
0.05). The age of conception was positively correlated with glucose ( = 0.57, <
0.01) and cholesterol ( = 0.68, < 0.001) at 9 mo. Our results show that a 0.7
kg/d gain from birth allowed the first breeding at 15 mo, 6 mo earlier than usual
for these conditions, without any negative effect on heifer reproductive
performance.
PMID- 26440168
TI - Impact of visual, olfactory, and auditory cues on circulating concentrations of
ghrelin in wethers.
AB - Ghrelin is a hormone that stimulates feed intake and regulates energy
homeostasis. A link has been observed in sheep, in which simulated feedings at
scheduled meal times resulted in an increase in ghrelin concentrations. The
present study sought to characterize the effect of feeding cues outside of
scheduled meal times on circulating ghrelin concentrations in sheep. Katahdin
wethers (age 201 +/- 4.9 d; weight 35 +/- 1.2 kg) were not offered feed (CONT; =
5), offered 275 g of feed (FED; = 5), or fitted with a muzzle and offered 275 g
of feed (SHAM; = 5) during the sampling period, which began 2.5 h after normally
scheduled daily feeding time. Blood samples were collected via jugular catheter
every 15 min for 2.5 h. Feed was offered for 15 min 0.5 h after the start of
blood sampling. The CONT samples were collected on d 1, and FED and SHAM samples
were collected on d 2. The active ghrelin present in the plasma was then analyzed
by RIA. After the Shapiro-Wilk W goodness of fit test demonstrated that 1 SHAM
wether was an outlier and it was removed, data were tested for effect of
treatment (FED, SHAM, or CONT), time, and treatment * time interaction using
procedures for repeated measures with JMP Software (SAS Inst. Inc., Cary, NC).
There was no treatment or time effect ( > 0.05); however, there was a treatment *
time interaction on plasma ghrelin concentrations ( = 0.0028) such that ghrelin
concentrations in SHAM wethers were greater than in CONT wethers 15, 60, and 90
min after feeding, whereas ghrelin concentrations in SHAM wethers were greater
than those in FED wethers 30, 60, 90, and 120 min after feeding ( < 0.05). Within
the SHAM treatment, ghrelin concentrations were greater at 15 min than at -30
min. Moreover, ghrelin concentrations within the FED treatment were greater at
30 min than at 30, 45, 60, 90, 105, and 120 min and at -15 min than at 15 through
120 min. The area under the curve representing circulating concentrations of
ghrelin in CONT, FED, and SHAM treatments, determined using the trapezoidal
method, yielded a treatment effect with a tendency toward significance ( =
0.0866). These results indicate plasma ghrelin concentrations in scheduled meal
fed wethers are elevated following visual, olfactory, and auditory feeding cues
outside of scheduled feeding times.
PMID- 26440169
TI - Pattern of gamma-glutamyl transferase activity in cow milk throughout lactation
and relationships with metabolic conditions and milk composition.
AB - The main objective of this experiment was to study the gamma-glutamyl transferase
(GGT) activity in milk during lactation and its relationship with metabolic
status of dairy cows, milk yield, milk composition, and cheesemaking properties.
The study was performed in a tied stall barn and involved 20 lactations from 12
healthy multiparous Italian Friesian dairy cows. During lactation starting at d
10, milk samples were collected weekly and analyzed for composition, somatic
cells count, titratable acidity, and milk coagulation properties. The GGT
activity was measured in defatted samples. Blood samples were collected weekly to
assess biochemical indicators related to energy, protein, and mineral metabolism,
markers of inflammation and some enzyme activities. The lactations of each cow
were retrospectively categorized into 2 groups according to their milk GGT
activity value through lactation. A median value of GGT activity in the milk of
all lactations was calculated (3,045 U/L), and 10 lactations with lower GGT
activity were classified as low while 10 lactations with greater GGT activity
were classified as high. The average value of milk GGT activity during lactation
was 3,863 and 3,024 U/L for high and low, respectively. The GGT activity
decreased in early lactation and reached minimum values in the second month
(3,289 and 2,355 U/L for high and low, respectively). Thereafter GGT activity
increased progressively, reaching values in late lactation of 4,511 and 3,540 U/L
in high and low, respectively. On average, milk yield was 40.81 and 42.76 kg/d in
high and low, respectively, and a negative partial correlation with milk GGT
activity was observed. A greater milk protein concentration was observed in high
(3.39%) compared with low (3.18%), and a positive partial correlation with milk
GGT activity was observed. Greater titratable acidity in high than that in low
(3.75 vs. 3.45 degrees Soxhlet-Henkel/50 mL, respectively) was also observed.
Plasma glucose was greater in cows of high than in low group, while plasma urea
was lower in the high than in the low group. No relationship between plasma GGT
and milk GGT activity was observed. Our results show an important effect of
lactation stage on milk GGT activity. The individual effect observed from
consecutive lactations and the relationship between milk GGT activity and milk
protein concentration in healthy cows could open prospects for GGT as a future
tool in improving milk protein content.
PMID- 26440170
TI - Blood parameters in fattening pigs fed whole-ear corn silage and housed in group
pens or in metabolic cages.
AB - The aim of this work was to evaluate the effects of the inclusion of whole-ear
corn silage (WECS) in diets for advanced fattening heavy pigs (substitution for
part of the dry corn and wheat bran) allocated or not in metabolic cages on the
main blood parameters. The high-moisture shelled corn is largely used in pig
feeding while WECS is less often used despite the fact that it increases the DM
crop yield. Three experimental diets were fed to 27 barrows (Italian Large White
* Italian Duroc), with an average BW of 98.2 (+/-5.6) kg at the start of the
trial, and randomly allotted to 3 experimental groups including a control diet
(CON) containing cereal meals (corn, barley, and wheat, 80.2% DM in total),
soybean meal (9% DM), wheat bran (8% DM), minerals and supplements (2.8% DM), and
2 diets containing WECS (15 or 30% DM referred to as 15WECS and 30WECS,
respectively) in partial or complete substitution for wheat bran and corn meal.
The pigs were randomly housed in 9 pens with 3 animals per pen and 3 pens per
dietary treatment. Six pigs per each of the 3 treatments were moved from the pens
to individual metabolic cages for 3 consecutive periods (2 pigs per treatment per
period). Each period lasted 14 d, and blood was collected at the start and at the
end of the periods. Blood was drawn from the jugular vein before feed
distribution in the morning, at 14 d intervals, and analyzed for hematological,
metabolic, and serum protein profiles. The effect of the metabolic cage housing
was included in the statistical model to compare the results obtained in the 2
different environments of restrained and group-housed barrows. The WECS affected
the neutrophil to lymphocyte ratio and mean corpuscular hemoglobin concentration.
The main diet effect on plasma metabolites was recorded for plasma NEFA, with
higher values in WECS diets compared with the CON. The metabolic cage housing
affected both hematological (red blood cell count, hemoglobin, hematocrit) and
metabolic (protein and its fractions) items, which can be markers of
hemodilution. These results indicate the possibility to use this feed in the diet
of heavy pigs without negative effects on physiology. The absolute values from
metabolic profile of pigs in metabolic cages must be considered with caution for
possible comparisons with values obtained on-field in group pens, particularly
because a different hemodilution may affect the results.
PMID- 26440171
TI - Effects of standardized ileal digestible tryptophan: lysine ratio on growth
performance of nursery pigs.
AB - Two experiments were conducted to estimate the standardized ileal digestible
(SID) Trp:Lys ratio requirement for growth performance of nursery pigs.
Experimental diets were formulated to ensure that lysine was the second limiting
AA throughout the experiments. In Exp. 1 (6 to 10 kg BW), 255 nursery pigs (PIC
327 * 1050, initially 6.3 +/- 0.15 kg, mean +/- SD) arranged in pens of 6 or 7
pigs were blocked by pen weight and assigned to experimental diets (7 pens/diet)
consisting of SID Trp:Lys ratios of 14.7%, 16.5%, 18.4%, 20.3%, 22.1%, and 24.0%
for 14 d with 1.30% SID Lys. In Exp. 2 (11 to 20 kg BW), 1,088 pigs (PIC 337 *
1050, initially 11.2 kg +/- 1.35 BW, mean +/- SD) arranged in pens of 24 to 27
pigs were blocked by average pig weight and assigned to experimental diets (6
pens/diet) consisting of SID Trp:Lys ratios of 14.5%, 16.5%, 18.0%, 19.5%, 21.0%,
22.5%, and 24.5% for 21 d with 30% dried distillers grains with solubles and
0.97% SID Lys. Each experiment was analyzed using general linear mixed models
with heterogeneous residual variances. Competing heteroskedastic models included
broken-line linear (BLL), broken-line quadratic (BLQ), and quadratic polynomial
(QP). For each response, the best-fitting model was selected using Bayesian
information criterion. In Exp. 1 (6 to 10 kg BW), increasing SID Trp:Lys ratio
linearly increased ( 0.05) ADG and G:F. For ADG, the best-fitting model was a QP
in which the maximum ADG was estimated at 23.9% (95% confidence interval [CI]:
[<14.7%, >24.0%]) SID Trp:Lys ratio. For G:F, the best-fitting model was a BLL in
which the maximum G:F was estimated at 20.4% (95% CI: [14.3%, 26.5%]) SID
Trp:Lys. In Exp. 2 (11 to 20 kg BW), increasing SID Trp:Lys ratio increased (
0.05) ADG and G:F in a quadratic manner. For ADG, the best-fitting model was a QP
in which the maximum ADG was estimated at 21.2% (95% CI: [20.5%, 21.9%]) SID
Trp:Lys. For G:F, BLL and BLQ models had comparable fit and estimated SID Trp:Lys
requirements at 16.6% (95% CI: [16.0%, 17.3%]) and 17.1% (95% CI: [16.6%,
17.7%]), respectively. In conclusion, the estimated SID Trp:Lys requirement in
Exp. 1 ranged from 20.4% for maximum G:F to 23.9% for maximum ADG, whereas in
Exp. 2 it ranged from 16.6% for maximum G:F to 21.2% for maximum ADG. These
results suggest that standard recommendations may underestimate the SID Trp:Lys
requirement for nursery pigs from 11 to 20 kg BW.
PMID- 26440172
TI - Effects of fiber inclusion on growth performance and nutrient digestibility of
piglets reared under optimal or poor hygienic conditions.
AB - Two experiments were conducted to study the effects of inclusion of additional
fiber in the Phase I diet on growth performance and nutrient digestibility in
piglets reared under "optimal" or "poor" hygienic conditions. In both
experiments, the design was completely randomized with a control diet that
contained 2.2% crude fiber and 8 additional isonutritive diets that included 2.5
or 5.0% of sugar beet pulp (SBP), straw, oat hulls (OH), or wheat middlings
(WHM). Preplanned polynomial contrasts were used to study the effects of 1) fiber
inclusion (control diet vs. average of the 8 fiber-containing diets), 2) source
of fiber, 3) level of fiber, and 4) interaction between source and level of
fiber. In Exp. 1 (clean barn), fiber inclusion increased ( < 0.01) the incidence
of postweaning diarrhea (PWD) and reduced ( < 0.05) feed efficiency and apparent
total tract digestibility (ATTD) of all nutrients except that of CP, which was
not affected. Piglet performance was not affected by source or level of dietary
fiber. The ATTD of all nutrients decreased ( < 0.05) as the level of fiber
increased and was lower in pigs fed straw or OH than in pigs fed SBP or WHM. The
apparent ileal digestibility of GE and DM decreased ( < 0.05) with fiber
inclusion, a reduction that was more pronounced ( < 0.05) with straw or SBP than
with OH inclusion, with WHM inclusion being intermediate. Fiber inclusion did not
affect villous height to crypt depth ratio of the ileum mucosa. The inclusion of
5% of a fiber source increased and counts in the cecum ( < 0.001) but the to
ratio was not affected. In Exp. 2 (dirty barn), fiber inclusion did not affect
piglet performance but tended to increase PWD ( = 0.07). Also, fiber inclusion
reduced ( < 0.05) the ATTD of all dietary components except that of CP, which was
not affected. Source and level of fiber did not affect ATTD of nutrients except
for DM, which was greater for pigs fed SBP than for pigs fed straw ( < 0.05). In
conclusion, in the current research, pigs reared under optimal hygienic
conditions had lower incidence of PWD, better growth performance, and greater DM
and GE digestibility than pigs reared under poor hygienic conditions. An excess
of dietary fiber was more detrimental for all these traits in piglets reared
under optimal hygienic conditions. The effects of the source and level of fiber
on piglet performance was limited in the 2 experiments.
PMID- 26440173
TI - Energy requirements for growth in male and female Saanen goats.
AB - The aim of this study was to investigate the energy requirements of female and
intact and castrated male Saanen goats. Animals were randomly assigned to 1 of 2
experiments designed to investigate the energy requirements for maintenance and
gain. To determine the maintenance requirements, 85 goats were used (26 intact
males, 30 castrated males, and 29 females) with an initial BW of 30.3 +/- 0.87
kg. Thirty goats (8 intact males, 9 castrated males, and 13 females) were
slaughtered to be used as the baseline group. The remaining goats were assigned
in a split-plot design using a 3 * 3 factorial arrangement (3 sexes-intact males,
castrated males, and females-and 3 DMI levels-ad libitum and restricted fed to 75
or 50% of the ad libitum intake). The NE was obtained using 65 goats (20 intact
males, 22 castrated males, and 23 females) fed ad libitum in a completely
randomized design. Eight intact males, 9 castrated males, and 13 females were
slaughtered at 30.5 +/- 1.53 kg BW. Seventeen goats (6 intact males, 6 castrated
males, and 5 females) were slaughtered at 38.1 +/- 0.49 kg BW. The remaining
goats were slaughtered at 44.0 +/- 0.50 kg BW. The NE did not differ between the
sexes ( = 0.59; 258.5 kJ/kg BW), resulting in a ME for maintenance of 412.4 kJ/kg
BW. The estimated energy use efficiency for maintenance was 0.627. During the
growth phase, NE differed between the sexes ( < 0.001); intact males, castrated
males, and females showed an average NE equal to 15.2, 18.6, and 22.7 MJ/kg of
empty weight gain, respectively. The energy requirements for growth differed
between the sexes. The difference was found to be due to distinct NE and partial
efficiency of ME utilization for growth in intact and castrated males and females
during the late growth phase. This study may contribute to adjustments in feeding
system energy recommendations regarding the NE and NE found for goats during the
late growth phase.
PMID- 26440174
TI - In vivo ruminal degradation characteristics and apparent digestibility of low
quality prairie hay for steers consuming monensin and Optimase.
AB - Seven ruminally cannulated crossbred steers (BW = 720 +/- 62 kg) were used in a
randomized crossover design (4 periods, each 18 d) to evaluate in vivo rumen
characteristics and apparent digestibility of steers consuming low-quality
prairie hay and 1 of 4 isonitrogenous protein supplements. Treatments included 1)
40% CP (DM basis) cottonseed meal and wheat middlings-based supplement (Control),
2) a cottonseed meal and wheat middlings-based supplement with slow-release urea
and a fibrolytic feed enzyme (Optimase; Alltech, Inc., Nicholasville, KY)
designed to replace 30% of plant-based CP provided in the Control (OPT), 3) the
Control plus 0.40 mg?kg BW?d monensin (Rumensin 90; Elanco Animal Health,
Greenfield, IN; MON), and 4) the OPT plus 0.40 mg?kg BW?d monensin (COMBO).
Steers were allowed ad libitum access to prairie hay (5.0% CP and 76% NDF) and
were provided each respective supplement at 0800 h daily at a rate of 1.0 g/kg of
BW. Steers were adapted to diets for 10 d before sample collection. Beginning on
d 11, DMI was measured and samples were collected to determine apparent
digestibility. On d 15 of the 18-d period, rumen fluid was collected 10 times
over a 24-h period. Forage DMI was greater ( <= 0.02) for steers consuming the
OPT compared with steers consuming the MON or COMBO, although forage DMI was not
different ( = 0.10) among steers consuming the Control compared with steers
consuming the OPT, MON, or COMBO. Steers fed the MON and COMBO had lower ( <=
0.05) passage rate compared with steers fed the Control and the OPT. The MON-fed
steers had lower ( = 0.01) ruminal pH and increased ( = 0.03) propionate as a
percentage of total VFA production. A time * treatment ( = 0.01) interaction was
observed for ruminal NH-N due to a rapid (0 to 1 h after feeding) increase
followed by a quick (1 to 4 h after feeding) decline in NH-N by steers consuming
the OPT and COMBO that was not observed for steers consuming all other
treatments. Apparent digestibility of DM ( = 0.01) and NDF ( = 0.03) were
improved for steers fed the COMBO supplement compared with steers consuming all
other experimental supplements. This work suggests that the OPT may be an
effective replacement for a portion of supplemental degradable intake protein in
low-quality forage. Further research is necessary to determine if the combination
of monensin and the Optimase consistently improves low-quality forage
utilization.
PMID- 26440175
TI - Using organic acids to control subacute ruminal acidosis and fermentation in
feedlot cattle fed a high-grain diet.
AB - The objective of this study was to determine whether supplementing organic acids
can prevent incidences of subacute ruminal acidosis (SARA) in beef heifers fed a
diet consisting of 8% barley silage and 92% barley grain-based concentrate (DM
basis). Ten ruminally cannulated Hereford crossbred heifers (484 +/- 25 kg BW)
were used in a replicated 5 * 5 Latin square design with 14-d periods including
10 d for dietary adaptation and 4 d for measurements. Dietary treatments included
no supplementation (Control), low fumaric acid (61 g/d), high fumaric acid (125
g/d), low malic acid (59 g/d), and high malic acid (134 g/d). Organic acid
supplementation had no effect on DMI ( = 0.77). Similarly, no effects were
observed on mean ( = 0.74), minimum ( = 0.64), and maximum ( = 0.27) ruminal pH
measured continuously for 48 h. Moreover, area under the curve for pH thresholds
6.2 ( = 0.97), 5.8 ( = 0.66), 5.5 ( = 0.55), and 5.2 ( = 0.93) was similar for
all treatments. However, malic acid supplementation lowered the amount of time
that ruminal pH was <6.2 compared with the Control ( = 0.02) and fumaric acid
treatments ( < 0.01). No effects were observed on total VFA concentrations with
organic acid supplementation ( = 0.98) compared with the Control, but greater
total VFA concentrations were observed with fumaric acid compared with the malic
acid treatments ( = 0.02). The population of total culturable bacteria 3 h after
feeding was reduced with supplemental malic acid compared with the Control ( =
0.03) and fumaric acid treatments ( = 0.03). However, no effects were observed
with organic acid supplementation on lactic acid-utilizing bacteria ( = 0.59). In
conclusion, under the conditions of the present study, organic acid
supplementation did not have any significant effects on ruminal fermentation
parameters compared with the Control and were not effective in preventing SARA in
beef cattle fed high-grain diets.
PMID- 26440176
TI - Effects of alternate day feeding of dried distiller's grains plus solubles in
forage-fed steers on intake, ruminal fermentation and passage rates, and serum
nonesterified fatty acid.
AB - Four ruminally and duodenally cannulated Holstein steers (BW = 449 +/- 7.3 kg)
were used to examine the effects of feeding either dried distiller's grains plus
solubles (DG) or grass hay on alternate days (every other day) on intake, ruminal
fermentation and passage rates, and serum NEFA in forage-fed steers. Steers were
assigned to 1 of 4 dietary treatments in a 4 * 4 Latin square: 1) only hay (CON),
2) hay and 0.4% of BW as DG DM daily (DG7), 3) hay daily and 0.8% BW DG every
other day (DG2), and 4) alternate day feeding of hay and 0.8% of BW as DG (DGA).
Treatment periods consisted of 13 d of adaptation and 8 d of collecting digesta
and blood. Over the entire collection period, DMI was decreased ( = 0.004) for
DGA compared with other treatments (13.0 +/- 0.8, 12.7 +/- 0.8, 13.3 +/- 0.8, and
10.9 +/- 0.8 kg/d for CON, DG7, DG2, and DGA, respectively). Immediately after
feeding on days supplement was fed to DG2 and DGA (supplemented days [SUP]),
ruminal pH of DGA was less than other treatments but by the end of the day was
greater than other treatments (treatment * time, < 0.001). At feeding time on
nonsupplemented days (NSUP), ruminal pH of DGA steers was greater than other
treatments but was similar (treatment * time, < 0.001) to DG2 and CON by 5 h
after feeding. Total concentrations of VFA were similar ( = 0.09) among
treatments on SUP; however, on NSUP, total VFA concentrations were least in DGA
from feeding until 4 h after feeding (treatment * time, = 0.02). No differences (
>= 0.06) were observed among treatments for apparent ruminal, total intestinal,
and total tract DM, OM, or CP digestibility. There were no differences ( = 0.36)
in serum NEFA among treatments on SUP; however, on NSUP, steers fed DGA (209.5 +/
12.7 m) had greater ( < 0.01) NEFA compared with other treatments (84.4 +/-
12.7, 88.0 +/- 12.7, and 77.7 +/- 12.7 m for CON, DG7, and DG2, respectively).
The DGA feeding strategy influenced DMI and ruminal kinetics and circulating NEFA
without impacting total tract digestibility.
PMID- 26440177
TI - Retention time of digesta in the gastrointestinal tract of growing Saanen goats.
AB - This study examined the effect of increased BW on mean retention time (MRT) of
both particulate and solute marker, gastrointestinal tract (GIT) development, and
fiber digestion in the whole tract of growing Saanen goats using the slaughter
technique. A total of 58 Saanen goats with initial BW of 15.7 +/- 0.9 kg were
allocated into 9 treatments with a 3 * 3 factorial arrangement consisting of 3
sexes (female, castrated males, and intact males) and 3 slaughter weights
(initial, intermediate, and final; target BW of 16, 23, and 30 kg at slaughter,
respectively). They were fed twice daily (0700 and 1600 h) with the identical
diets for ad libitum intake. Mean retention time of particulate matter was
estimated by in situ determination of indigestible NDF (iNDF), and the MRT of
solute marker was determined by Cr-EDTA. Treatment effects were evaluated in a
split-plot design, with sex as the main plot and slaughter weight as the subplot.
Orthogonal polynomial contrasts were used to determine linear and quadratic
effects of slaughter weight, whereas the effect of sex was compared using the
Tukey test. The effects of sex and sex * slaughter weight were not significant
for most of variables evaluated. The results showed that DMI (% BW) linearly
decreased as slaughter weight increased ( < 0.01). Generally wet weight of the
total GIT tissues (% BW) decreased and digesta pool sizes (g) linearly increased
with increasing slaughter weight ( <= 0.05). The ratio of iNDF:NDF for both
ingested diet and reticulorumen digesta linearly increased as slaughter weight
increased ( <= 0.05). The MRT of particles did not change with increasing
slaughter weight ( = 0.94). Mean retention time of particulate matter linearly
increased in the omasum but linearly decreased in the abomasum with increasing
slaughter weight ( < 0.01). Mean retention time of solute marker in the
forestomachs linearly increased with increasing slaughter weight ( < 0.01). The
results revealed a decreased selectivity with increasing BW, as supported by a
greater ratio of iNDF:NDF for ingested diet. Increasing BW led to neither a
longer particle MRT in the reticulorumen nor a digestive advantage. The results
also indicated that, on average, 91% of fiber digestion occurred in the
forestomachs of the goats.
PMID- 26440178
TI - The effect of restricted milk feeding through conventional or step-down methods
with or without forage provision in starter feed on performance of Holstein bull
calves.
AB - The objective of the current study was to examine whether step-down (STP) milk
feeding method together with forage provision would improve performance, rumen
fermentation, nutrient digestibility, blood metabolites, and structural growth of
calves. Holstein bull calves ( = 40) were randomly assigned to 1 of 4 treatments
in a completely randomized design with a 2 * 2 factorial arrangement. Treatments
were 1) conventional (COV) milk feeding without forage provision (COV-NF), 2) COV
milk feeding with forage provision, 3) STP milk feeding without forage provision,
and 4) STP milk feeding with forage provision. Calves in the COV method ( = 20)
received 5.5 L/d milk until d 56 of age followed by 2 L/d milk from d 56 to 59 of
age. Calves in the STP method ( = 20) received 7 L/d milk until d 35, 4 L/d milk
from d 35 to 48, and 2 L/d milk from d 50 to 59 of age. All the calves received
the starter ration from d 3 of the study until d 74 of age. Forage-supplemented
calves ( = 10/milk feeding method) received 15% alfalfa hay mixed with finely
ground starter as a total mixed ration. All calves were weaned on d 60 of age and
remained in the study until d 74. Regardless of the milk feeding method, the
final BW (92.54 vs. 83.14 kg/d), starter intake (0.90 vs. 0.65 kg/d), total DMI
(1.43 vs. 1.17 kg/d), and ADG (0.73 vs. 0.60 kg/d) were greater ( < 0.01) in
forage-supplemented calves than those that received no forage during the
preweaning, postweaning, and overall periods. Milk feeding method had no effect
on ruminal pH, total VFA, acetate, or acetate:propionate ratio as well as body
measurements. Ruminal pH and the molar proportions of acetate were greater ( <
0.05) in the forage-supplemented calves than those that received no forage during
the pre- and postweaning periods. Regardless of forage provision, STP methods
increased ( < 0.05) the postweaning numbers of monocytes and lymphocytes.
Overall, there was no interaction between milk feeding methods and forage
provision with respect to BW, DMI, G:F, apparent nutrient digestibility (DM, OM,
and CP), and body measurements. The interaction of milk feeding method and forage
provision was significant for the rumen concentration of butyrate ( < 0.05), with
the highest concentration for the COV-NF treatment on d 35 of the study. In
conclusion, independent of the milk feeding method, inclusion of 15% alfalfa hay
in starter diets enhances the performance of dairy calves.
PMID- 26440179
TI - Effect of dietary fat concentration from condensed corn distillers' solubles,
during the growing phase, on beef cattle performance, carcass traits,
digestibility, and ruminal metabolism.
AB - The objectives of this study were to determine the effect of fat concentration
from corn distillers' solubles (CDS), fed during the growing phase, on DMI, gain,
carcass traits, digestibility, ruminal metabolism, and methane emissions of
steers. In Exp. 1, 40 steers (age = 136 +/- 20 d; BW = 185 +/- 11 kg) were
randomly allotted to 1 of 5 dietary treatments: 1) a cosrn-based gro?wing diet
(CNT), 2) 0% CDS, 3) 10% CDS, 4) 19% CDS, or 5) 27% CDS. Diets 2 through 5
included coproducts (corn gluten feed and soybean hulls) and were formulated to
achieve fat concentrations of 3, 5, 7, and 9%, respectively. Diets were fed once
daily for 106 d (growing phase). All steers were fed a corn-based diet from d 107
to 196. Contrasts were used to examine 1) the difference between CNT and 10% CDS
and 2) linear and quadratic effects of CDS inclusion. During the growing phase,
steers fed CNT had increased ( < 0.01) ADG and G:F compared with steers fed 10%
CDS. Increasing CDS inclusion increased (linear, <= 0.02) ADG and G:F. Overall,
steers fed CNT had increased ( < 0.01) ADG compared with steers fed 10% CDS, but
increasing CDS inclusion had no effect ( = 0.19) on overall ADG. Overall DMI and
G:F were not different ( >= 0.16) in any contrast. There was a trend (Linear; =
0.08) for ultrasound marbling at d 196 to increase as CDS inclusion increased;
however, there were no effects ( >= 0.20) of treatment on carcass marbling or
quality grade. In Exp. 2, 5 steers (BW = 335 +/- 56 kg) were fed Exp. 1 diets for
ad libitum intakes in a 5 * 5 Latin square design. Apparent DM digestibility
increased (linear, = 0.02) with increasing dietary CDS inclusion. Steers fed CNT
had greater ( = 0.01) DM digestibility than those fed 10% CDS. Fat digestibility
increased (linear, < 0.01) in steers with increasing CDS, but NDF and ADF
digestibility were not affected ( >= 0.17) by treatment. Similarly, ruminal pH
and VFA concentrations were not affected ( >= 0.13). Also, there was no
difference ( >= 0.37) in ruminal methane emissions (g/h). In conclusion, feeding
corn during the growing phase increased overall ADG compared with 10% CDS
coproduct-based diet but did not affect carcass traits or methane production.
Increasing dietary fat inclusion from CDS in coproduct-based diets linearly
increased DM and fat digestibility and predicted marbling scores via ultrasound
but did not affect marbling at slaughter, NDF digestibility, propionate, or
methane production.
PMID- 26440180
TI - Effects of feeding processed corn stover and distillers grains on growth
performance and metabolism of beef cattle.
AB - Objectives were to evaluate the effects of replacing corn in feedlot finishing
diets with processed corn stover (CS), processed by various combinations of
chemical and physical methods, and modified wet distillers grain with solubles
(MWDGS) on growth performance, carcass characteristics, digestibility, and
ruminal metabolism of cattle. Corn stover was physically processed (ground or
extruded) and chemically processed with alkaline agents (CaO and NaOH) to reduce
the crystallinity of the lignocellulosic structure. In Exp. 1 steers ( = 18,
initial BW = 385 +/- 32 kg) and heifers ( = 41, initial BW = 381 +/- 27 kg) were
allotted to 1 of 5 dietary treatments: 1) 55% dry, cracked corn, 35% MWDGS, 5%
vitamin-mineral supplement, and 5% untreated ground CS (), 2) CS treated with 5%
CaO (DM basis) and stored in an Ag-Bag (BGCS), 3) CS treated with 5% CaO (DM
basis) and extruded (5 EXCS), 4) CS treated with 4% CaO and 1% NaOH (DM basis)
and extruded (4,1 EXCS), or 5) CS treated with 3% CaO and 2% NaOH (DM basis) and
extruded (3,2 EXCS). Extruded CS was hydrated to 34% moisture, then an additional
16% water was added, as a solution carrying CaO or NaOH or both, via a calibrated
pump during processing through a dual-shafted encased extruder (Readco Kurimoto
Continuous Processor, York, PA) with the desired exiting temperature of 76.7
degrees C +/- 2.8 degrees C. All treated CS diets contained 20% CS and 40% MWDGS
(DM basis) to replace 20% corn when compared to CON. There were no effects ( >=
0.20) of dietary treatment on ADG, G:F, 12th-rib back fat, marbling score, LM
area, or yield grade. However, cattle fed CON had increased ( = 0.02) DMI
compared to cattle fed the treated CS diets. In Exp. 2, using the same diets as
fed in Exp. 1, ruminally cannulated steers ( = 5; initial BW = 417 +/- 21 kg)
were fed for 90% of ad libitum intake in a 5 * 5 Latin square design. Apparent
digestibility of NDF and ADF increased ( < 0.01) when cattle were fed treated CS
diets compared with CON, regardless of the treatment applied. Ruminal pH was
reduced ( = 0.02) in cattle fed BGCS from 0 to 6 h postfeeding compared with
cattle fed all other diets. Cattle fed the treated CS diets had the greatest ( <
0.01) mean acetate concentrations, which increased ( = 0.01) total VFA
concentrations. Replacing a portion of the corn with treated CS in feedlot diets
containing MWDGS increased fiber digestibility without affecting feedlot cattle
gain, efficiency, marbling score, or LM area.
PMID- 26440181
TI - Changes in lipid metabolism and beta-adrenergic response of adipose tissues of
periparturient dairy cows affected by an energy-dense diet and nicotinic acid
supplementation.
AB - Dairy cattle will mobilize large amounts of body fat during early lactation as an
effect of decreased lipogenesis and increased lipolysis. Regulation of lipid
metabolism involves fatty acid synthesis from acetate and beta-adrenergic
stimulated phosphorylation of hormone-sensitive lipase (HSL) and perilipin in
adipocytes. Although basic mechanisms of mobilizing fat storage in transition
cows are understood, we lack a sufficiently detailed understanding to declare the
exact regulatory network of these in a broad range of dairy cattle. The objective
of the present study was to quantify 1) protein abundance of fatty acid synthase
(FAS), 2) extent of phosphorylation of HSL and perilipin in vivo, and 3) beta
adrenergic stimulated lipolytic response of adipose tissues in vitro at different
stages of the periparturient period. We fed 20 German Holstein cows an energy
dense or an energetically adequate diet prepartum and 0 or 24 g/d nicotinic acid
(NA) supplementation. Biopsy samples of subcutaneous and retroperitoneal adipose
tissue were obtained at d 42 prepartum (d -42) and at d 1, 21, and 100 postpartum
(d +1, d +21, d +100, respectively). To assess beta-adrenergic response, tissue
samples were incubated with 1 MU isoproterenol for 90 min at 37 degrees C. The
NEFA and glycerol release, as well as HSL and perilipin phosphorylation, was
measured as indicators of in vitro stimulated lipolysis. In addition, protein
expression of FAS and extent of HSL and perilipin phosphorylation were measured
in fresh, nonincubated samples. There was no effect of dietary energy density or
NA on the observed variables. The extent of HSL and perilipin phosphorylation
under isoproterenol stimulation was strongly correlated with the release of NEFA
and glycerol, consistent with the functional link between beta-adrenergic
stimulated protein phosphorylation and lipolysis. In the nonincubated samples,
FAS protein expression was decreased at d +1 and d +21, whereas HSL and perilipin
phosphorylation increased from d -42 to d +1 and remained at an increased level
throughout the first 100 d of lactation. In vitro lipolytic response was
significant in prepartum samples at times when in vivo lipolysis was only
minimally activated by phosphorylation. These data extend our understanding of
the complex nature of control of lipolysis and lipogenesis in dairy cows and
could be useful to the ongoing development of systems biology models of
metabolism to help improve our quantitative knowledge of the cow.
PMID- 26440182
TI - Effect of flint corn processing method and roughage level on finishing
performance of Nellore-based cattle.
AB - This study was conducted to evaluate the effects of flint corn processing method
(CPM) and level of NDF from roughage (rNDF) on performance, carcass
characteristics, and starch utilization by finishing Nellore-based cattle fed
high-concentrate, flint corn-based diets. In this study, 112 Nellore type bulls
(initial BW 384.07 +/- 29.53 kg and 24-36 mo of age) were individually fed using
Calan gates or individual pens. The animals were used in a randomized complete
block design in a 2 * 4 factorial arrangement with 2 CPM, high-moisture flint
corn (HMC) or finely ground dry flint corn (FGC), with 1 of 4 levels of rNDF, 3,
8, 13, and 18% (DM basis), using sugarcane silage (SS) as roughage. Bulls were
adapted to the finishing diet over a 21-d period and fed for a total of 81 d.
Fecal starch (FS) concentration was determined on d 46 and 74 of the feeding
period. There was a quadratic effect of rNDF on final BW ( < 0.01) and ADG ( =
0.01). Optimal concentrations of rNDF were estimated using the first derivative
of second order polynomials, indicating that final BW and ADG were maximized with
13.3 and 13.0% rNDF, respectively. An interaction was observed between CPM and
rNDF ( = 0.05) for DMI, with peak DMI occurring at 11.3 and 13.7% rNDF with FGC
and HMC, respectively. Cattle fed HMC had 13.9% greater G:F ( < 0.01) compared
with those fed FGC (0.172 vs. 0.151, respectively). There were quadratic effects
of rNDF on HCW ( = 0.04) and ME intake ( < 0.01); heaviest carcass weights were
estimated, in both cases, to be achieved with 12.8% rNDF. A quadratic effect of
rNDF for renal, pelvic, and inguinal fat weight ( = 0.04) was observed, with a
peak estimated to occur at 12.6% rNDF. An interaction between CPM and rNDF also
was observed for FS ( < 0.05). Bulls fed FGC with 3% rNDF had greater FS content,
and FS linearly decreased as concentration of rNDF increased. For bulls fed HMC,
FS was 3.0% of DM and was unaffected by rNDF in the diet. Lower FS from bulls fed
HMC suggests that availability of starch from flint corn was greater than that of
FGC. For Nellore-based cattle fed a flint corn-based diet containing SS and 8%
whole lint cottonseed, performance was optimized with 12.8% rNDF. In the absence
of cottonseed addition to diets, optimal performance would be expected with about
14.5% rNDF.
PMID- 26440183
TI - Effects of Juniperus species and stage of maturity on nutritional, in vitro
digestibility, and plant secondary compound characteristics.
AB - Rising feed costs and recurring feed shortages necessitate the investigation into
alternative and underutilized feed resources. Nutritional characteristics of
species are either unknown or limited to leaves and ground material from small
stems. Therefore, the objective was to quantify nutritional characteristics, 48-h
true IVDMD (tIVDMD), microbial gas production, and secondary compound
characteristics of entire woody plant material of 4 species-, , , and -at
immature and mature stages of growth. Immature plants had greater CP
concentrations and lower NDF concentrations ( < 0.001) than mature plants
regardless of species. Mature plants also had greater ( < 0.001) concentrations
of ADF compared with immature plants with the exception of . In general, immature
, , and had greater ( < 0.02) tIVDMD and total 48-h and asymptotic gas production
than mature plants. Immature and plants were more digested (tIVDMD; < 0.001) than
immature and , but tIVDMD did not differ in mature plant material across species.
Condensed tannins (CT) were greater ( < 0.001) in immature and than mature
plants; differences in CT concentrations among immature species were also
detected ( < 0.04). Volatile oil yields were similar across maturity and species
with 1 exception: immature yielded more ( < 0.02) volatile oil than mature
material. Volatile oil composition across species varied and contained a range of
65 to 70 terpene compounds. The dominant terpenes across species were generally
greater ( < 0.05) in immature vs. mature plant material with the exception of .
Labdane acids were negligible in , , and and greater in ( < 0.001). Ground
material from mature juniper species, although inferior in nutritional quality
compared with immature plants, is comparable to traditional low-quality roughage
ingredients. Given that has been successfully fed in lamb feedlot diets, the
similarities of , and suggest that all three species have potential to be
effective roughage ingredients.
PMID- 26440184
TI - Expression of alpha-tocopherol-associated genes and alpha-tocopherol accumulation
in Japanese Black (Wagyu) calves with and without alpha-tocopherol
supplementation.
AB - The aim of the study was to clarify 1) the distribution of 6 alpha-tocopherol
(alpha-Toc)-associated gene expressions in 20 major tissues, including metabolic,
reproductive, endocrine, immune, and digestive and absorptive tissues, in
relation to alpha-Toc status and 2) the change in expression patterns of the
genes induced when alpha-Toc was orally administered to Japanese Black (JB)
calves. This study examined weaned male JB calves ( = 10), of which 5 calves were
orally administered alpha-Toc for 2 wk (30 IU.kg BW.d; TOC group). The others did
not receive the alpha-Toc supplement and were the control (CONT) group. The 20
tissues and venous blood (serum) were sampled on the final day. In both groups,
the mean mRNA expression levels for alpha-Toc transfer protein, afamin (AFM), ATP
binding cassette transporter A1, and tocopherol-associated protein were greatest
in the liver ( < 0.05), whereas scavenger receptor class B, Type I (SR-BI) mRNA
was greatest in the adrenal gland ( < 0.05). The gene for cytochrome P450 family
4, subfamily F, polypeptide 2 was most highly expressed in the liver, testes, and
adrenal gland. The alpha-Toc content was greatest ( < 0.05) in the testes of the
20 sampled tissues in the CONT group. However, the levels in the testes and
jejunum were similar and greater ( < 0.05) than the levels in the other 18
tissues in the TOC group. The mean increase in alpha-Toc levels after oral alpha
Toc administration (mean alpha-Toc content for the TOC group divided by the CONT
group content) were greater ( < 0.05) in the jejunum (40.7-fold) and duodenum and
liver (26.3- and 23.1-fold) than in the serum (7.8-fold). In the liver, alpha-Toc
administration significantly increased ( < 0.05) the AFM and SR-BI mRNA
expression levels. The results show that the liver may play an important role in
the regulation of alpha-Toc disposition, but other peripheral tissues that
accumulate large amounts of alpha-Toc could moderate the local alpha-Toc status
and functions, as inferred from the high expressions of the alpha-Toc-associated
genes in JB calves.
PMID- 26440185
TI - Effect of slow-release urea inclusion in diets containing modified corn
distillers grains on total tract digestibility and ruminal fermentation in
feedlot cattle.
AB - Ruminal degradable intake protein (DIP) deficit may result when cattle are fed
diets containing a greater inclusion of processed corn grain and small to
moderate inclusion of corn distillers grains (DG). This deficit may arise from
greater proportions of rapidly fermentable carbohydrates and RUP in corn grain.
Urea-derived N is 100% DIP; however, rates of degradation of carbohydrates and
conventional urea (CU) may not match. Therefore, beneficial effects may result
from the use of slow-release urea (SRU) sources over CU when added to DIP
deficient diets. An experiment was conducted to evaluate the effect of increasing
DIP concentration through inclusion of 1 of 2 SRU sources or CU in DG-containing
feedlot diets on ruminal fermentation and total tract digestibility. In addition,
an in situ experiment was conducted to characterize N disappearance of urea
sources from polyester bags. Four ruminally cannulated steers (initial BW = 588
+/- 8 kg) were arranged in a 4 * 4 Latin square design and assigned randomly to 1
of 4 dietary treatments containing 0% (CON) or 0.6% urea in the form of CU (UREA)
or SRU as Optigen II (polymer-encapsulated urea; OPTI) or NitroShure (lipid
encapsulated urea; NITRO), and 30% corn earlage, 20% modified corn DG with
solubles, 7.8% corn silage, 4.3% dry supplement, and dry-rolled corn (DM basis).
Dietary DIP was estimated at 6.6% and 8.3% for CON and urea-containing dietary
treatments, respectively. Steers were fed ad libitum once daily. Differences in
purine derivatives-to-creatinine (PDC) index between treatments were used as
indicators of differences in microbial CP synthesis. Intake of OM, digestibility
of OM, NDF, CP, and starch, ruminal pH, total VFA ruminal concentration, and PDC
index were not affected by treatment ( >= 0.21). Concentration of ammonia-N
noticeably peaked at 4 h after feed delivery for cattle fed UREA (treatment *
time, = 0.06) and measured at least 5.5 mg/dL for any treatment and at any hour
after feed delivery. During the first 12 h after incubation, N disappearance was
greater for CU and NitroShure than Optigen II (urea source * time, < 0.01).
Supplementing DIP through inclusion of CU or SRU did not affect feed intake,
digestibility, or most of the ruminal fermentation parameters evaluated, which
may relate to the lack of need of urea supplementation in the present experiment.
More research is warranted to evaluate the use of SRU in DIP-deficient diets.
PMID- 26440186
TI - Impact of synthetic antioxidants on lipid peroxidation of distiller's dried
grains with solubles and distiller's corn oil stored under high temperature and
humidity conditions.
AB - This experiment evaluated the effect of antioxidants, oil content in distiller's
dried grains with solubles (DDGS), quality of distiller's corn oil, and storage
time on lipid peroxidation. A source of low-oil DDGS (LO-DDGS; 5.0% ether extract
[EE], as-fed basis), high-oil DDGS (HO-DDGS; 13.0% EE, as-fed basis), and 2
sources of distiller's corn oil (DCO; 1.20, 0.08, and 0.48% moisture, insoluble
impurities, and unsaponifiables [MIU], respectively [DCO-1], and 1.20, 0.01, and
0.10% MIU, respectively [DCO-2]) were obtained. Each of the 4 ingredients was
divided into 18 representative subsamples (approximately 908 g for DDGS or 2 kg
of DCO). Six subsamples of each ingredient were mixed with either no supplemental
antioxidants (CON), Rendox-CQ (REN; 1,000 mg/kg EE; Kemin, Industries, Des
Moines, IA), or Santoquin-Q4T (SAN; 1,500 mg/kg EE; Novus International, St.
Louis, MO). Each mixture ( = 72) was split into thirds, and 1 portion was
immediately frozen at -20 degrees C (d 0). Two portions were stored under hot
(38.6 +/- 0.1 degrees C) and humid conditions (94.0 +/- 0.3% relative humidity)
for 14 or 28 d. The MIXED procedure of SAS was used to evaluate the effects of
ingredient, antioxidant, storage time, and interactions, with d-0 values used as
a covariate. From d 14 to 28, peroxide value (PV), -anisidine value (AnV), and
thiobarbituric acid reactive substances (TBARS) of DCO and DDGS increased by 3-
to 4-fold ( < 0.05). Over the entire storage period, PV of DCO-1 and HO-DDGS
(12.3 +/- 0.3 and 12.6 +/- 0.3 mEq O/kg oil, respectively) exceeded ( < 0.05)
that of DCO-2 and LO-DDGS (9.6 +/- 0.3 and 9.3 +/- 0.3 mEq O/kg oil,
respectively). Adding REN or SAN ( < 0.05) reduced TBARS and AnV relative to CON
(TBARS = 11.0 +/- 0.2 mg malondialdehyde Eq/kg oil and AnV = 6.5 +/- 0.2) over
the entire period (mean of d 14 and 28), but TBARS and AnV did not differ ( >
0.05) between antioxidants (TBARS = 6.1 +/- 0.2 and 5.9 +/- 0.2 mg
malondialdehyde Eq/kg oil, respectively, and AnV = 1.9 +/- 0.2 and 1.8 +/- 0.2
for REN and SAN, respectively). The PV on d 14 and 28 and overall was less ( <
0.05) when either antioxidant was added relative to CON (16.0 mEq O/kg) and was
greater for ingredients treated with SAN ( < 0.05) compared with REN (8.8 +/- 0.2
and 8.0 +/- 0.2 mEq O/kg oil for SAN and REN, respectively). In summary,
antioxidants reduced peroxidation of DDGS and DCO by approximately 50% during 28
d of storage at 38.6 degrees C and 94.0% relative humidity, but neither
antioxidant completely stabilized the ingredients.
PMID- 26440187
TI - Temporary confinement of loose-housed hyperprolific sows reduces piglet
mortality.
AB - The objective of this study was to investigate piglet mortality in a commercial
setting where sows were accommodated in a loose-housed system with an option to
confine the sow for a few days around farrowing and during early lactation. The
study was conducted in a Danish piggery where records were obtained from 2,139
farrowings. Sows were randomly allocated to 1 of 3 treatments: loose-loose (LL),
loose-confined (LC), and confined-confined (CC). In LL, sows were loose housed
from the time they entered the farrowing pens to weaning. In LC, sows were loose
housed until farrowing was finished and then confined to d 4 after farrowing. In
CC, sows were confined at d 114 of gestation to d 4 after farrowing. All sows
were loose housed from d 5 to weaning. Total piglet mortality was analyzed at
batch level to include piglets fostered by nurse sows and at sow level to analyze
the effects of confinement during different time periods. Total piglet mortality
was greater in LL (26.0%) and LC (25.4%) compared with CC (22.1%; < 0.001). The
proportion of stillborn piglets was not different between treatments ( = 0.21)
but a larger proportion was crushed in LL (10.7%) compared with LC (9.7%; =
0.03), which again was greater than CC (7.8%; < 0.001). Piglet mortality before
equalization was lower in CC (3.7%) than in LL (7.5%) and LC (7.0%; < 0.001).
Confinement reduced mortality from litter equalization to d 4 (7.6% for LL vs.
6.7% for LC; = 0.01) but more so in CC (5.6%) than in LC ( < 0.001). From d 4 to
weaning, LL had lower mortality (5.6%) than LC (6.9%) and CC (6.6%; = 0.01). A
larger proportion of sows in CC were classified as "low mortality" compared with
LL and LC both before ( < 0.001) and after ( = 0.002) litter equalization. The
results in this study emphasize that the period of time from the birth of the
first piglet to litter equalization is important in relation to piglet mortality.
The results also suggest that confinement for 4 d after farrowing can reduce
mortality in this specific period, but only confinement from d 114 of gestation
to d 4 after farrowing reduced total piglet mortality.
PMID- 26440188
TI - Effect of growth implant regimen on health, performance, and immunity of high
risk, newly received stocker cattle.
AB - Growth implant efficacy may be affected when administered to nutritionally
stressed calves, whereas the procedure may alter health or the humoral immune
response to respiratory vaccination. The study objective was to determine the
effect of different administration times (d 0, 14, or 28) of a growth implant
containing 200 mg progesterone and 20 mg estradiol benzoate on health,
performance, and metabolic and immunologic variables in high-risk, newly received
beef calves used in a 120-d receiving/grazing stocker system. Crossbred bull and
steer calves ( = 203) were weighed (initial BW = 203 +/- 2.7 kg), stratified by
castrate status on arrival, and randomly assigned to experimental treatments
consisting of 1) negative control (no growth implant administered), 2) growth
implant administered on d 0, 3) growth implant administered on d 14, and 4)
growth implant administered on d 28. There were no differences ( >= 0.16) in BW
or ADG during the 42-d receiving period. However, ADG during the subsequent
grazing period and overall was greater ( <= 0.01) for implanted calves versus the
negative control. Growth implant timing did not affect the rate of clinical
bovine respiratory disease morbidity ( = 0.52; 94% morbidity overall) or bovine
viral diarrhea virus type 1a antibody titer concentration ( = 0.61). Indicative
of an overall negative energy balance on arrival, NEFA decreased sharply
subsequent to d 0 (day effect, < 0.001), but was not affected ( = 0.47) by the
timing of growth implantation. Blood urea N concentrations increased transiently
(day effect, < 0.001); however, no treatment effect was observed ( = 0.72).
Therefore, under conditions of this study, the timing of growth implant
administration did not affect growth implant efficacy, health, or metabolic or
immunologic variables in newly received, high-risk beef stocker calves. Overall,
our observations suggest that there is not a clear benefit to delaying growth
implantation and that a growth implant does not affect health or vaccine response
in newly received beef calves.
PMID- 26440189
TI - Toxicity of endophyte-infected ryegrass hay containing high ergovaline level in
lactating ewes.
AB - The symbiotic association of var. (formerly named ) with perennial ryegrass ()
leads to the production of ergovaline (EV) and lolitrem B (LB) that are toxic for
livestock. The objectives of this study were to determine the effects of feeding
endophyte-infected ryegrass (SE+) hay on 16 lactating ewes (BW 80 +/- 10 kg) in
comparison with endophyte-free ryegrass (SE-) hay to investigate the putative
mechanisms of action of EV and LB and to evaluate their persistence in milk and
animal tissues. The mean EV and LB concentrations in SE+ hay were 851 and 884
MUg/kg DM, respectively, whereas these alkaloids were below the limit of
detection in SE- hay. No effect of SE+ was observed on animal health and skin
temperature whereas prolactin decreased and significant differences between hays
were observed from d 7 to 28 of the study ( < 0.03) but had no effect on milk
production. Hematocrit and biochemical analyses of plasma revealed no significant
difference between SE+ and SE-, whereas cortisol concentration differed
significantly on d 28 ( = 0.001). Measurement of oxidative damage and antioxidant
enzyme activities in plasma, liver, and kidneys revealed a slight increase in
some enzyme activities involved in defense against oxidative damage in the SE+
fed ewes. Slight variations in the activities of hepatic and kidney flavin
monooxygenase enzymes were observed, whereas in the kidney, glutathione
transferase activity decreased significantly ( = 0.002) in the SE+ fed ewes,
whereas uridine diphosphate glucuronosyltransferase activity increased ( =
0.001). After 28 d of exposure of ewes to the SE+ hay, low EV and LB
concentrations were measured in tissues. The highest concentration of EV was
observed in the liver (0.68 MUg/kg) whereas fat contained the highest
concentration of LB (2.39 MUg/kg). Both toxins were also identified at the trace
level in milk.
PMID- 26440190
TI - Technical note: Evaluation of a system for monitoring individual feeding behavior
and activity in beef cattle.
AB - Behavioral observations are important to detect illness in beef cattle. However,
traditional observation techniques are time and labor intensive and may be
subjective. The objective was to validate a system for monitoring individual
feeding behavior and activity in beef cattle (Fedometer [FEDO]; ENGS, Rosh Pina,
Israel). Sixteen steers (initial BW +/- SD = 326 +/- 46 kg) were fitted with data
loggers (FEDO) on their left front leg and housed in a pen with a feedbunk
equipped with an antenna emitting an electromagnetic field that reached 30 +/- 2
cm in front of the feedbunk. Feedbunk attendance (duration of visit and frequency
of meals) measured by FEDO was compared with live observations (27 observational
periods lasting between 72 and 240 min; mean 126 min). Lying time and frequency
of lying bouts were compared with previously validated accelerometers fitted to
the hind leg (10 steers equipped for 10 to 12 d; HOBO Pendant G Acceleration Data
Logger [HOBO]; Onset Computer Corporation, Pocasset, MA). Step counts were
compared with video recordings (15 observations for 6-min intervals in 6 steers).
Concordance correlation coefficients (CCC), accounting for repeated measures, and
limits of agreement were computed. Comparison between FEDO and observed time at
the feedbunk yielded a CCC of 0.98 (95% confidence interval [CI] 0.97-0.99). All
68 meal events observed were recorded by FEDO. However, FEDO recorded 4 meal
events during the 27 observational periods that were not observed. Lying time
measured by HOBO and FEDO were highly correlated (CCC = 0.98; 95% CI 0.97-0.99).
However, frequency of lying bouts measured by FEDO was only moderately correlated
to HOBO (CCC = 0.71; 95% CI 0.63-0.77); FEDO underestimating the number of lying
bouts (on average, 0.4 fewer bouts per 6 h). Step count by FEDO was moderately
correlated to video observations (CCC = 0.75; 95% CI 0.49-0.89); FEDO
overestimating the number of steps (on average, 5 more steps per 6 min). In
conclusion, the FEDO system accurately measured duration of feedbunk attendance,
frequency of meals, and lying time. However, it overestimated the number of steps
and underestimated the frequency of lying bouts.
PMID- 26440191
TI - Determination of value of bovine respiratory disease control using a remote early
disease identification system compared with conventional methods of metaphylaxis
and visual observations.
AB - Mitigation of the deleterious effects of bovine respiratory disease (BRD) is an
important issue in the cattle industry. Conventional management of calves at high
risk for BRD often includes mass treatment with antimicrobials at arrival
followed by visual observation for individual clinical cases. These methods have
proven effective; however, control program efficacy is influenced by the accuracy
of visual observation. A remote early disease identification (REDI) system has
been described that monitors cattle behavior to identify potential BRD cases. The
objective of this research was to compare health and performance outcomes using
either traditional BRD control (visual observation and metaphylaxis) or REDI
during a 60-d postarrival phase in high-risk beef calves. The randomized
controlled clinical trial was performed in 8 replicates at 3 different facilities
over a 19-mo period. In each replicate, a single load of calves was randomly
allocated to receive either conventional management (CONV; total = 8) or REDI
(total = 8) as the method for BRD control. Cattle were monitored with each
diagnostic method for the first 30 d on feed and performance variables were
collected until approximately 60 d after arrival. Statistical differences ( <
0.10) were not identified in common performance (ADG) or health (morbidity, first
treatment success, and mortality risk) among the treatment groups. Calves in the
REDI pens had a lower ( < 0.01) average number of days on feed at first treatment
(9.1 +/- 1.2 d) compared with CONV pens (15.8 +/- 1.2 d). There were no
statistical differences ( > 0.10) in risk of BRD treatment and REDI calves were
not administered antimicrobials at arrival; therefore, REDI calves had a lower (
< 0.01) average number of doses of antimicrobials/calf (0.75 +/- 0.1 doses)
compared with CONV calves (1.67 +/- 0.1 doses). In this trial, the REDI system
was comparable to conventional management with the potential advantages of
earlier BRD diagnosis and decreased use of antimicrobials. Further research
should be performed to evaluate the longer-term impacts of the 2 systems.
PMID- 26440192
TI - Effect of surgical castration with or without oral meloxicam on the acute
inflammatory response in yearling beef bulls.
AB - Pain management and welfare are increasingly prevalent concerns within animal
agriculture. Analgesics may alleviate pain and inflammation associated with
castration of beef cattle. This study was conducted to elucidate the effects of
surgical castration on the acute inflammatory response and immunomodulation and
whether concurrent oral administration of meloxicam (1 mg/kg BW) would alter
these responses. On d -1, crossbred bull calves ( = 30; initial BW = 227.4 +/-
10.3 kg) were fitted with indwelling jugular catheters and rectal temperature
(RT) recording devices, placed into individual stanchions, and randomly assigned
to 1 of 3 treatments. Treatment application occurred at h 0 and consisted of 1)
intact bull calves treated with sham castration (CON), 2) bulls surgically
castrated without meloxicam administration (CAS), and 3) bulls surgically
castrated with oral meloxicam (1 mg/kg BW) administration (MEL). Blood samples
were collected at 0.5-h intervals from h -2 to 4, 1.0-h intervals from h 4 to 8,
and 12-h intervals from h 12 to 72. Serum was analyzed for cortisol and
haptoglobin (Hp) concentrations using ELISA. Whole blood was analyzed for
complete blood counts at -2, 0, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 h, and RT
was recorded in 5-min intervals. Postcastration RT was greatest for MEL (39.04),
intermediate for CAS (38.99), and least for CON (38.93 degrees C; <= 0.01). Serum
cortisol was increased ( < 0.001) for CAS (12.3) and MEL (11.3) compared with CON
(6.7 ng/mL) during the postcastration period. At 0.5 and 1.5 h, cortisol
concentration was greater in CAS and MEL than CON, whereas at 2 and 2.5 h,
cortisol concentration was greatest for CAS, intermediate for MEL, and least for
CON (treatment * time, < 0.001). Total white blood cell ( <= 0.04), lymphocyte (
<= 0.02), and monocyte ( <= 0.002) counts were greatest for CAS, intermediate for
MEL, and least for CON. Administration of MEL reduced ( <= 0.002) eosinophil
counts during the postcastration period when compared with CON and CAS. The
change in serum Hp, relative to baseline values, was reduced for MEL at 36 ( <
0.01) and 60 h ( <= 0.03), and the overall Hp concentration was least for MEL ( <
0.001). Oral administration of meloxicam at the time of castration reduced the
acute inflammatory response in castrates, as evidenced by a reduction in Hp and
certain leukocyte concentrations; it also caused a delayed increase in RT.
Further research is needed to determine if this reduced acute inflammatory
response would equate to improved health and/or performance after castration.
PMID- 26440193
TI - Postweaning substitution of grazed forage with a high-energy concentrate has
variable long-term effects on subcutaneous fat and marbling in Bos taurus
genotypes.
AB - The objective of this study was to quantify the effects and interactions of stage
of growth and genotype on commercial carcass traits and intramuscular fat (IMF)
content in 5 muscles of steers ( = 165) and to test the hypothesis that
substituting pasture with a high-energy concentrate during the immediate
postweaning period increases IMF. Cattle of 3 genotypes (Angus, Hereford, and
Wagyu * Angus; = 55/genotype) were selected at weaning from commercial herds,
targeting genotypic differences in marbling and subcutaneous fatness. Following
weaning, steers were fed for 168 d within 2 different improved, temperate pasture
based nutritional systems: a forage-only system (FS) and forage with high-energy
supplemented system (SS), with 2 replicates per system. The supplement was fed at
a level of 1% of average BW adjusted every 2 wk to provide an estimated 50% of
energy requirements for 168 d from weaning. Pasture on offer in both systems was
managed to match the BW of the FS and SS steers during the postweaning treatment
period to avoid confounding due to differences in growth rate during this period.
Steers were then regrouped into 2 replicates and backgrounded on improved,
temperate pasture for 158 d and then grain fed within 1 group for 105 d (short
fed) or 259 d (long fed). Groups were slaughtered at commencement (d 0) and end
of postweaning nutritional treatments (d 168), end of backgrounding (d 326), and
after short (d 431) or long feedlotting (d 585). Serial slaughter stage had an
effect on all traits assessed ( < 0.01). The FS steers had more rib fat ( < 0.01)
and higher Meat Standards Australia marbling score ( < 0.05) and a tendency ( <
0.10) to have greater eye muscle area than the SS steers throughout the study.
Genotypic differences were evident ( < 0.05) for all traits assessed except HCW,
dressing percentage, rib fat depth, ossification score, ultimate pH, and IMF in
the semitendinosus muscle. The results for marbling and IMF do not support the
use of a high-energy feed as a substitute for an equivalent amount of energy from
pasture during the immediate postweaning period to enhance development of
marbling.
PMID- 26440194
TI - The effect of a limit-fed diet and slow-feed hay nets on morphometric
measurements and postprandial metabolite and hormone patterns in adult horses.
AB - Modern horse management systems tend to limit a horse's opportunity to forage,
rely on meal feeding, and may contribute to the increase in equine obesity. The
use of slow-feed hay nets represents an opportunity to extend foraging time while
feeding a restricted diet. The objectives of this study were to determine if
limit feeding combined with a slow-feed hay net would affect morphometric
measurements and postprandial metabolite and hormone patterns in overweight adult
horses. Eight adult Quarter horses (BW 563 kg +/- 4.6 kg; BCS 7.2 +/- 0.3) were
used in a randomized complete block design, with 4 horses assigned to feeding hay
off the stall floor (FLOOR) and 4 horses assigned to feeding from a slow-feed hay
net (NET). Horses were fed in individual stalls at 1% BW each day, split evenly
between 2 meals at 0700 and 1600 h. Body weight, BCS, neck and girth
circumference, cresty neck score, and ultrasound measurements of average rump
fat, longissimus dorsi (LD) depth, and LD thickness were taken on d 0, 14, and
28. Three 24-h blood samplings were conducted on d 0, 14, and 28 and were
analyzed for glucose, insulin, cortisol, and leptin concentrations. Samplings
occurred every 30 min for 3 h postfeeding, with hourly samples occurring between
feedings. Horses feeding from the FLOOR took less time to consume their hay meal
compared with horses feeding from the NET ( < 0.001). All horses lost weight over
the 28-d period ( < 0.0001); however, no difference was observed between
treatments. There was no difference in BCS, neck and girth circumference, cresty
neck score, rump fat, or LD depth between days or treatments ( >= 0.25). There
was an effect of day on LD thickness in horses feeding from the NET. Longissimus
dorsi thickness was lower on d 28 compared with that on d 0 ( = 0.0257). Only
time to peak insulin and peak cortisol were affected by treatment ( <= 0.037),
with horses feeding from the NET having lower values than horses feeding from the
FLOOR. Average glucose, insulin, cortisol, and leptin were affected by day ( <=
0.0102). Glucose and insulin values increased, whereas cortisol and leptin levels
decreased throughout the 28-d study. The use of a slow-feed hay net coupled with
a limit-fed diet appears to be an effective method for decreasing BW and
maintaining more homeostatic levels of postprandial metabolites and hormones when
feeding overweight adult horses.
PMID- 26440195
TI - Effects of supplementation during late gestation on goat performance and behavior
under rangeland conditions.
AB - This study evaluated the effects of peripartum feed supplementation on doe and
kid BW and BCS, milk yield and composition, serum metabolites, and maternal
neonatal behavior under rangeland conditions in northern Mexico. Adult does ( =
23) were randomly assigned to 3 nutritional plane groups: 1) goats supplemented
(500 g of concentrate [18% CP/kg DM, 2.7 Mcal/kg DM, and 2% salt]) from 15 d
prepartum to 7 d postpartum (G15; = 8), 2) the same supplementation as G15 but
from 35 d before until 7 d after kidding (G35; = 8), and 3) nonsupplemented does
(GC; = 7). Supplemented goats differed from GC goats in BW (48 +/- 1.8, 46.1 +/-
2.5, and 44.9 +/- 2.3 kg; < 0.05), milk yield (1.8 +/- 0.1, 1.9 +/- 0.2, and 1.2
+/- 0.1 kg at d 15 postpartum; < 0.01), kid birth weights (3.8 +/- 0.2, 3.6 +/-
0.2, and 3.4 +/- 0.2 kg; < 0.05), and kid BW at 15 d after birth (6.9 +/- 0.2,
6.6 +/- 0.2, and 5.6 +/- 0.2 kg; < 0.05) for the G35, G15, and GC, respectively.
Serum concentrations for total protein, glucose, and cholesterol were not
affected ( > 0.05) by treatments. Milk of GC goats showed increased ( < 0.05)
percentages for fat, protein, lactose, and nonfat milk solids, whereas total
quantities of these variables where higher ( < 0.05) in the G15 and G35 groups.
Furthermore, GC dams spent more time seeking their offspring and emitted more low
pitched bleats 4 h postpartum ( < 0.05) in a 2-choice test compared with the G15
and G35 groups. In general, peripartum supplementation promoted a closer dam-kid
relationship at 8 h postpartum. Goat performance may be improved in this semiarid
region of Mexico with marginal production through supplementation in late
gestation.
PMID- 26440196
TI - The economic and environmental value of genetic improvements in fattening pigs:
An integrated dynamic model approach.
AB - The selection of animals for improved performance affects the profitability of
pig fattening and has environmental consequences. The goal of this paper was to
examine how changes in genetic and market parameters impact the biophysical
(feeding patterns, timing of slaughter, nitrogen excretion) and economic (return
per pig space unit) results describing pig fattening in a Finnish farm. The
analysis can be viewed as focusing on terminal line breeding goals. An integrated
model using recursive stochastic dynamic programming and a biological pig growth
model was used to estimate biophysical results and economic values. Combining
these models allowed us to provide more accurate estimates for the value of
genetic improvement and, thus, provide better feedback to animal breeding
programs than the traditional approach, which is based on fixed management
patterns. Besides the benchmark scenario, the results were simulated for 5 other
scenarios. In each scenario, genotype was improved regarding daily growth
potential, carcass lean meat content, or the parameters of the Gompertz growth
curve (maturing rate [], adult weight of protein [alpha], and adult weight of
lipid mass []). The change in each parameter was equal to approximately 1 SD
genetic improvement (ceteris paribus). Increasing , , daily growth potential, or
carcass lean meat content increased the return on pig space unit by ?12.60,
?7.60, ?4.10, or ?2.90 per year, respectively, whereas an increase in decreased
the return by ?3.10. The genetic improvement in and resulted in the highest
decrease in nitrogen excretion calculated in total or per kilogram of carcass
gain but only under the optimal feeding pattern. Simulated changes in the
Gompertz growth function parameters imply greater changes in ADG and lean meat
content than changes in scenarios focusing on improving ADG and lean meat content
directly. The economic value of genetic improvements as well as the quantity of
nitrogen excreted during the fattening period largely depends on feeding.
Improved genotypes can require changes in pig management pattern. Estimating the
influence of the genotype on the nitrogen excretion without considering changes
in the management pattern can result in flawed conclusions. To improve overall
economic performance and to decrease the environmental footprint of fattening pig
production, the pig producer can adjust the herd management pattern according to
the pigs' genetics.
PMID- 26440197
TI - Effects of diet form and feeder adjustment on growth performance of nursery and
finishing pigs.
AB - Three experiments were conducted to determine the effects of feeder adjustment
and diet form on growth performance of nursery (Exp. 1 and 2) and finishing (Exp.
3) pigs. Treatments were arranged as a 2 * 3 factorial with the main effects of
feeder adjustment and diet form. The 2 feeder adjustments were a narrow and wide
feeder adjustment (minimum gap opening of 1.27 and 2.54 cm, respectively). The 3
diet forms were meal, poor-quality pellets (70% pellets and 30% fines for Exp. 1
and 2 and 50% pellets and 50% fines for Exp. 3), and screened pellets with
minimal fines (3 to 10%). In Exp. 1, 210 pigs (initially 11.9 kg BW) were used in
a 21-d trial with 7 pigs per pen and 5 pens per treatment. No feeder adjustment *
diet form interactions were observed. There were no differences in ADG, ADFI, or
G:F due to feeder adjustment. Pigs fed the meal diet had increased ( < 0.05) ADG
and ADFI compared with pigs fed the poor-quality or screened pellets. Pigs fed
meal or poor-quality pellets had decreased ( < 0.05) G:F compared with pigs fed
screened pellets. In Exp. 2, 1,005 nursery pigs (initially 14.1 kg BW) were used
in a 28-d trial with 26 to 28 pigs per pen and 6 pens per treatment. Pigs fed
from the narrow feeder adjustment had decreased ( < 0.05) ADG and ADFI compared
with pigs fed from the wide adjustment with no differences in G:F. Pigs fed the
meal diet had decreased ( < 0.05) ADG compared with pigs fed poor-quality or
screened pellets. Pigs fed meal or poor-quality pellets had decreased ( < 0.05)
G:F compared with pigs fed screened pellets. In Exp. 3, 246 pigs (initially 56.8
kg BW) were used in a 69-d trial with 5 pens per treatment and 6 or 7 pigs per
pen. Overall, ADFI decreased ( < 0.05) and G:F increased ( < 0.05) for pigs fed
from the narrow adjusted feeders compared with the wide adjustment with no
differences in ADG. Overall, pigs fed meal diets tended to have decreased ( <
0.10) ADG and had decreased ( < 0.05) G:F compared with pigs fed screened
pellets; ADG and G:F in those fed poor-quality pellets were intermediate. Feeding
meal or poor-quality pellets increased ( < 0.05) ADFI compared with pigs fed
screened pellets. In conclusion, feeding nursery pigs from a wide feeder gap may
increase ADG and ADFI with no negative effects on G:F. For finishing pigs,
reducing feeder gap reduced feed disappearance and improved G:F. In all
experiments, the greatest G:F improvements from pelleting were observed when the
percentage of fines was minimized.
PMID- 26440198
TI - The effect of administering multiple doses of tall larkspur (Delphinium barbeyi)
to cattle.
AB - Larkspurs ( spp.) are one of the most serious toxic plant problems on foothill
and mountain rangelands in the western United States. A considerable amount of
research has been conducted over the years in both field and pen settings. The
results of these research efforts have significantly increased our understanding
of the poisoning of cattle by larkspurs. However, most of the pen studies
conducted thus far have used a dosing regimen of a single bolus dose, which does
not accurately mimic the manner by which cattle are poisoned by larkspur while
grazing. Consequently, the objective of this study was to evaluate the acute
toxicity of tall larkspur ( collected near Manti, UT) when administered in
multiple doses, with the intent to identify a no observable adverse effect level
(NOAEL). The adverse effect selected for this study was muscle weakness to the
point the cattle could no longer remain ambulatory as would be required in a
grazing environment, thus becoming sternally recumbent when exercised. Hereford
steers were administered various doses of tall larkspur at 12-h intervals for 4 d
or until they showed marked signs of muscle weakness. The results suggest that a
dose of 2 mg kg?d -(methylsuccinimido) anthranoyllycoctonine (MSAL)-type
alkaloids is the NOAEL for a tall larkspur population with a norditerpenoid
alkaloid profile containing 4 mg MSAL-type alkaloids/g plant material and 12 mg
non-MSAL-type alkaloids/g plant material. Additionally, a computer model was
generated to simulate multiple-dosing regimens at the various doses as well as
different dosing regimens. The results from this study suggest that a 500-kg
steer can consume a daily dose of 1.25 kg of fresh tall larkspur (with a similar
alkaloid profile) without becoming severely poisoned (suffering from muscle
weakness to the point of recumbency). Additionally, these results indicate that a
serum concentration of approximately 355 ng methyllycaconitine/mL may represent a
toxic threshold.
PMID- 26440199
TI - Carbon flux assessment in cow-calf grazing systems.
AB - Greenhouse gas (GHG) fluxes and soil organic carbon (SOC) accumulation in
grassland ecosystems are intimately linked to grazing management. This study
assessed the carbon equivalent flux (Ceq) from 1) an irrigated, heavily stocked,
low-density grazing system, 2) a nonirrigated, lightly stocked, high-density
grazing system, and 3) a grazing-exclusion pasture site on the basis of the GHG
emissions from pasture soils and enteric methane emissions from cows grazing
different pasture treatments. Soil organic carbon and total soil nitrogen stocks
were measured but not included in Ceq determination because of study duration and
time needed to observe a change in soil composition. Light- and heavy-stocking
systems had 36% and 43% greater Ceq than nongrazed pasture sites, respectively (
< 0.01). The largest contributor to increased Ceq from grazing systems was
enteric CH emissions, which represented 15% and 32% of the overall emissions for
lightly and heavily stocked grazing systems, respectively. Across years, grazing
systems also had increased nitrous oxide (N2O; < 0.01) and CH emissions from
pasture soils ( < 0.01) compared with nongrazed pasture sites but, overall,
minimally contributed to total emissions. Results indicate no clear difference in
Ceqflux between the grazing systems studied when SOC change is not incorporated (
= 0.11). A greater stocking rate potentially increased total SOC stock ( = 0.02),
the addition of SOC deeper into the soil horizon ( = 0.01), and soil OM content
to 30 cm ( < 0.01). The incorporation of long-term annual carbon sequestration
into the determination of Ceq could change results and possibly differentiate the
grazing systems studied.
PMID- 26440200
TI - Effect of different dietary energy on collagen accumulation in skeletal muscle of
ram lambs.
AB - Tenderness is one of the most appreciated characteristics of meat quality. The
objective of this trial was to investigate the effect of different energy diets
on collagen deposition and meat tenderness. Twelve one-half Dorper * one-half
small thin-tailed sheep crossed ram lambs (20 +/- 0.5 kg of BW) were randomly
selected and divided into 2 groups in a completely randomized design. Animals
were offered identical diets at 100 or 65% of ad libitum intake. Lambs were
euthanized when BW in the ad libitum group reached 35 kg, and the semitendinosus
(ST) muscle were sampled. The results showed that Warner-Bratzler shear force
(WBSF) was significantly increased when lambs were fed an energy-restricted diet
( < 0.05). Masson trichrome stain and hydroxyproline assay demonstrated increased
collagen content in ST muscle of feed restriction lambs. Both and mRNA contents
were significantly increased when lambs were fed an energy-restricted diet ( <
0.05), whereas no difference for mRNA expression was observed ( > 0.05).
Expression of alpha () was greater in the feed restriction group ( < 0.01), and
no differences were observed for both () and () mRNA contents ( > 0.05). In
addition, 1, 2, 9, and 13 (, , , and ) did not change with the feed restriction,
whereas both 1 and 2 ( and ) were increased. Feed restriction did not alter TGF
beta and SMAD protein contents, but phosphor-p38 protein content was elevated. In
summary, feed restriction enhanced collagen accumulation in ST muscle, which may
negatively affect the lamb tenderness, and was associated with the upregulated
p38 signaling pathway.
PMID- 26440201
TI - Titanium-zirconium narrow-diameter versus titanium regular-diameter implants for
anterior and premolar single crowns: 3-year results of a randomized controlled
clinical study.
AB - AIM: To test whether titanium-zirconium (Ti-Zr) 3.3 mm diameter implants perform
differently from titanium (Ti) 4.1 mm diameter implants with respect to marginal
bone level (MBL) and clinical parameters. MATERIAL AND METHODS: Forty patients in
need of a single-implant crown in the anterior or premolar regions were enrolled
in two centres. Following random allocation, either a Ti-Zr or a Ti implant was
inserted. Porcelain-fused-to-metal crowns were inserted 6 months after
implantation. Implant survival, change in MBL, clinical parameters, change in mid
facial mucosa and papilla levels, and the occurrence of biological and technical
complications were assessed at the 3-year follow-up. RESULTS: At 3 years, 32 of
the 40 included patients were examined (15 Ti and 17 Ti-Zr implants). There were
no implant failures. From the implant placement to 3 years, the median change in
mean MBL amounted to 0.21 mm (mean: -0.31) in the Ti group and 0.10 mm (mean:
0.40) in the Ti-Zr group. There were no significant differences between the
groups with respect to the change in MBL, the change in mucosa levels, and the
occurrence of complications. CONCLUSIONS: Ti-Zr implants with 3.3 mm diameter
used for the support of single crowns in the anterior and the premolar regions
did not differ from Ti implants with 4.1 mm diameter regarding the clinical
performance over a 3-year period.
PMID- 26440202
TI - Switchable Bioelectrocatalysis Controlled by Dual Stimuli-Responsive Polymeric
Interface.
AB - The engineering of bionanointerfaces using stimuli-responsive polymers offers a
new dimension in the design of novel bioelectronic interfaces. The integration of
electrode surfaces with stimuli-responsive molecular cues provides a direct
control and ability to switch and tune physical and chemical properties of
bioelectronic interfaces in various biodevices. Here, we report a dual-responsive
biointerface employing a positively responding dual-switchable polymer,
poly(NIPAAm-co-DEAEMA)-b-HEAAm, to control and regulate enzyme-based
bioelectrocatalysis. The design interface exhibits reversible activation
deactivation of bioelectrocatalytic reactions in response to change in
temperature and in pH, which allows manipulation of biomolecular interactions to
produce on/off switchable conditions. Using electrochemical measurements, we
demonstrate that interfacial bioelectrochemical properties can be tuned over a
modest range of temperature (i.e., 20-60 degrees C) and pH (i.e., pH 4-8) of the
medium. The resulting dual-switchable interface may have important implications
not only for the design of responsive biocatalysis and on-demand operation of
biosensors, but also as an aid to elucidating electron-transport pathways and
mechanisms in living organisms by mimicking the dynamic properties of complex
biological environments and processes.
PMID- 26440203
TI - Efficacy of metformin on pregnancy complications in women with polycystic ovary
syndrome: a meta-analysis.
AB - OBJECTIVE: To evaluate the efficacy of metformin administration throughout
pregnancy on pregnancy-related complications in women with polycystic ovary
syndrome (PCOS). STUDY DESIGN: MEDLINE and ScienceDirect were searched to
retrieve relevant trials. The endpoint was the incidence of complications of
pregnancy, gestational diabetes mellitus (GDM), pre-eclampsia (PE), miscarriage
and premature birth included. RESULTS: Five studies with 502 PCOS patients with
metformin administration throughout pregnancy and 427 controls who used metformin
just to get conception were included in our meta-analysis. In study group, a
significantly lower change of emerging miscarriage and premature birth was
observed, the pooled relative risk (RR) was 0.32 (95% confidence interval (CI):
0.19-0.56) for miscarriage and 0.40 (95%CI: 0.18-0.91) for premature birth. No
significant difference was demonstrated in emerging GDM and PE. CONCLUSIONS:
Metformin therapy throughout pregnancy can reduce the RR of miscarriage and
premature birth incidence in PCOS patients with no serious side effects.
PMID- 26440204
TI - Aminoketyl Radicals in Organic Synthesis: Stereoselective Cyclization of Five-
and Six-Membered Cyclic Imides to 2-Azabicycles Using SmI2-H2O.
AB - Synthetic application of aminoketyl radicals [R-C(*)(O(-))NR'R"] formed by a
direct electron capture into the amide bond is limited. Herein, we demonstrate
addition of aminoketyl radicals to unactivated alkenes using SmI2-H2O as a
crucial promoter based on the generic five- and six-membered imide template.
Notably, this method enables direct access to aminoketyl radicals with wide
ranging applications in synthesis for the formation of C-C bonds adjacent to
nitrogen via polarity reversal.
PMID- 26440205
TI - Advances in Urinary Tract Endoscopy.
AB - The use of endoscopy in veterinary medicine has become the mainstay of diagnosis
and treatment in the subspecialty of small animal urology over the past decade.
This subspecialty is termed endourology. With the common incidence of urinary
tract obstructions, stones disease, renal disease, and urothelial malignancies,
combined with the recognized invasiveness and morbidity associated with
traditional surgical techniques, the use of endoscopic-assisted alternatives
using interventional endoscopic techniques has become appealing to both owners
and clinicians. This article provides a brief overview of some of the most common
urologic procedures being performed in veterinary medicine.
PMID- 26440206
TI - Identification of a Single Strand Origin of Replication in the Integrative and
Conjugative Element ICEBs1 of Bacillus subtilis.
AB - We identified a functional single strand origin of replication (sso) in the
integrative and conjugative element ICEBs1 of Bacillus subtilis. Integrative and
conjugative elements (ICEs, also known as conjugative transposons) are DNA
elements typically found integrated into a bacterial chromosome where they are
transmitted to daughter cells by chromosomal replication and cell division. Under
certain conditions, ICEs become activated and excise from the host chromosome and
can transfer to neighboring cells via the element-encoded conjugation machinery.
Activated ICEBs1 undergoes autonomous rolling circle replication that is needed
for the maintenance of the excised element in growing and dividing cells. Rolling
circle replication, used by many plasmids and phages, generates single-stranded
DNA (ssDNA). In many cases, the presence of an sso enhances the conversion of the
ssDNA to double-stranded DNA (dsDNA) by enabling priming of synthesis of the
second DNA strand. We initially identified sso1 in ICEBs1 based on sequence
similarity to the sso of an RCR plasmid. Several functional assays confirmed Sso
activity. Genetic analyses indicated that ICEBs1 uses sso1 and at least one other
region for second strand DNA synthesis. We found that Sso activity was important
for two key aspects of the ICEBs1 lifecycle: 1) maintenance of the plasmid form
of ICEBs1 in cells after excision from the chromosome, and 2) stable acquisition
of ICEBs1 following transfer to a new host. We identified sequences similar to
known plasmid sso's in several other ICEs. Together, our results indicate that
many other ICEs contain at least one single strand origin of replication, that
these ICEs likely undergo autonomous replication, and that replication
contributes to the stability and spread of these elements.
PMID- 26440207
TI - Isolation and characterization of Clostridium difficile in farm animals from
slaughterhouse to retail stage in Isfahan, Iran.
AB - To determine the prevalence of Clostridium difficile in farm animals from
slaughterhouse through to retail stage, a total of 750 samples of feces,
posteviscerated and washed carcass were collected from cattle, camels, goats, and
sheep in Isfahan, Iran. The overall prevalence of C. difficile in feces,
posteviscerated and washed carcass were 20 (13.3%), 23 (15.3%), and 11 (7.3%),
respectively; while C. difficile was isolated from 79 (26.3%) retail samples.
Twenty-nine (3.8%) isolates were toxigenic, with most toxigenic isolates (n = 17,
5.6%) identified from the retail stage. All toxigenic isolates harbored tcdA and
tcdB; however, all were negative for cdtB. The 29 isolates were classified into
21 different ribotypes. This study revealed evidence of existence of toxigenic C.
difficile in farm animal feces and meat in Iran.
PMID- 26440208
TI - Dogs Can Be Successfully Trained to Alert to Hypoglycemia Samples from Patients
with Type 1 Diabetes.
AB - INTRODUCTION: Hypoglycemia (Hypo) is the most common side effect of insulin
therapy in people with type 1 diabetes (T1D). Over time, patients with T1D become
unaware of signs and symptoms of Hypo. Hypo unawareness leads to morbidity and
mortality. Diabetes alert dogs (DADs) represent a unique way to help patients
with Hypo unawareness. Our group has previously presented data in abstract form
which demonstrates the sensitivity and specificity of DADS. The purpose of our
current study is to expand evaluation of DAD sensitivity and specificity using a
method that reduces the possibility of trainer bias. METHODS: We evaluated 6 dogs
aging 1-10 years old who had received an average of 6 months of training for Hypo
alert using positive training methods. Perspiration samples were collected from
patients during Hypo (BG 46-65 mg/dL) and normoglycemia (BG 85-136 mg/dl) and
were used in training. These samples were placed in glass vials which were then
placed into 7 steel cans (1 Hypo, 2 normal, 4 blank) randomly placed by roll of a
dice. The dogs alerted by either sitting in front of, or pushing, the can
containing the Hypo sample. Dogs were rewarded for appropriate recognition of the
Hypo samples using a food treat via a remote control dispenser. The results were
videotaped and statistically evaluated for sensitivity (proportion of lows
correctly alerted, "true positive rate") and specificity (proportion of blanks +
normal samples not alerted, "true negative rate") calculated after pooling data
across all trials for all dogs. RESULTS: All DADs displayed statistically
significant (p value <0.05) greater sensitivity (min 50.0%-max 87.5%) to detect
the Hypo sample than the expected random correct alert of 14%. Specificity ranged
from a min of 89.6% to a max of 97.9% (expected rate is not defined in this
scenario). CONCLUSIONS: Our results suggest that properly trained DADs can
successfully recognize and alert to Hypo in an in vitro setting using smell
alone.
PMID- 26440209
TI - LC-MS/MS analysis reveals a broad functional spectrum of proteins in the
secretome of sebocytes.
PMID- 26440210
TI - Xenopus borealis as an alternative source of oocytes for biophysical and
pharmacological studies of neuronal ion channels.
AB - For the past 30 years, oocytes from Xenopus laevis have been extensively used to
express and characterise ion channels in an easily controlled environment. Here
we report the first use of oocytes from the closely related species Xenopus
borealis as an alternative expression system for neuronal ion channels. Using the
two-electrode voltage-clamp technique, we show that a wide variety of voltage-
and ligand-gated ion channels have the same channel properties and
pharmacological profiles when expressed in either X. laevis or X. borealis
oocytes. Potential advantages of the X. borealis oocytes include a smaller
endogenous chloride current and the ability to produce more intense fluorescence
signals when studied with voltage-clamp fluorometry. Scanning electron microscopy
revealed a difference in vitelline membrane structure between the two species,
which may be related to the discrepancy in fluorescence signals observed. We
demonstrate that X. borealis oocytes are a viable heterologous system for
expression of neuronal ion channels with some potential advantages over X. laevis
oocytes for certain applications.
PMID- 26440211
TI - Bilayered vascular graft derived from human induced pluripotent stem cells with
biomimetic structure and function.
AB - BACKGROUND: We developed an aligned bi-layered vascular graft derived from human
induced pluripotent stem cells (iPSCs) that recapitulates the cellular
composition, orientation, and anti-inflammatory function of blood vessels.
MATERIALS & METHODS: The luminal layer consisted of longitudinal-aligned
nanofibrillar collagen containing primary endothelial cells (ECs) or iPSC-derived
ECs (iPSC-ECs). The outer layer contained circumferentially oriented
nanofibrillar collagen with primary smooth muscle cells (SMCs) or iPSC-derived
SMCs(iPSC-SMCs). RESULTS: On the aligned scaffolds, cells organized F-actin
assembly within 8o from the direction of nanofibrils. When compared to randomly
oriented scaffolds, EC-seeded aligned scaffolds had significant reduced
inflammatory response, based on adhesivity to monocytes. CONCLUSION: This study
highlights the importance of anisotropic scaffolds in directing cell form and
function, and has therapeutic significance as physiologically relevant blood
vessels.
PMID- 26440213
TI - Adaptations of skeletal muscle mitochondria to exercise training.
AB - Mitochondrial volume density (Mito(VD)) is composed of two distinct mitochondrial
subpopulations--intermyofibrillar mitochondria (Mito(IMF)) and subsarcolemmal
mitochondria (Mito(SS)). With exercise training, Mito(VD) may increase by up to
40% and is, for the most part, related to an increase in Mito(IMF). Exercise
induced adaptations in mitochondrial function depend on the intensity of training
and appear to be explained predominately by an increased expression of
mitochondrial enzymes that facilitate aerobic metabolism. Although mitochondrial
content often increases with training, it seems that mitochondrial adaptations
are not needed to facilitate maximal oxygen uptake, whereas such adaptations are
of greater importance for endurance capacity.
PMID- 26440212
TI - Serum antibodies to human leucocyte antigen (HLA)-E, HLA-F and HLA-G in patients
with systemic lupus erythematosus (SLE) during disease flares: Clinical relevance
of HLA-F autoantibodies.
AB - T lymphocyte hyperactivity and progressive inflammation in systemic lupus
erythematosus (SLE) patients results in over-expression of human leucocyte
antigen (HLA)-Ib on the surface of lymphocytes. These are shed into the
circulation upon inflammation, and may augment production of antibodies promoting
pathogenicity of the disease. The objective was to evaluate the association of
HLA-Ib (HLA-E, HLA-F and HLA-G) antibodies to the disease activity of SLE. The
immunoglobulin (Ig)G/IgM reactivity to HLA-Ib and beta2m in the sera of 69
German, 29 Mexican female SLE patients and 17 German female controls was measured
by multiplex Luminex((r))-based flow cytometry. The values were expressed as mean
flourescence intensity (MFI). Only the German SLE cohort was analysed in relation
to the clinical disease activity. In the controls, anti-HLA-G IgG predominated
over other HLA-Ib antibodies, whereas SLE patients had a preponderance of anti
HLA-F IgG over the other HLA-Ib antibodies. The disease activity index, Systemic
Lupus Erythematosus Disease Activity Index (SLEDAI)-2000, was reflected only in
the levels of anti-HLA-F IgG. Anti-HLA-F IgG with MFI level of 500-1999 was
associated with active SLE, whereas inactive SLE revealed higher MFI (>2000).
When anti-HLA-F IgG were cross-reactive with other HLA-Ib alleles, their
reactivity was reflected in the levels of anti-HLA-E and -G IgG. The prevalence
of HLA-F-monospecific antibodies in SLE patients was also associated with the
clinical disease activity. Anti-HLA-F IgG is possibly involved in the clearance
of HLA-F shed from lymphocytes and inflamed tissues to lessen the disease's
severity, and thus emerges as a beneficial immune biomarker. Therefore, anti-HLA
Ib IgG should be considered as a biomarker in standard SLE diagnostics.
PMID- 26440214
TI - ACC/AHA/STS Statement on the Future of Registries and the Performance Measurement
Enterprise: A Report of the American College of Cardiology/American Heart
Association Task Force on Performance Measures and The Society of Thoracic
Surgeons.
PMID- 26440215
TI - Patient-Centered Medical Home Features and Health Care Expenditures of Medicare
Beneficiaries with Chronic Disease Dyads.
AB - Three out of 4 Medicare beneficiaries have multiple chronic conditions, and
managing the care of this growing population can be complex and costly because of
care coordination challenges. This study assesses how different elements of the
patient-centered medical home (PCMH) model may impact the health care
expenditures of Medicare beneficiaries with the most prevalent chronic disease
dyads (ie, co-occurring high cholesterol and high blood pressure, high
cholesterol and heart disease, high cholesterol and diabetes, high cholesterol
and arthritis, heart disease and high blood pressure). Data from the 2007-2011
Medical Expenditure Panel Survey suggest that increased access to PCMH features
may differentially impact the distribution of health care expenditures across
health care service categories depending on the combination of chronic conditions
experienced by each beneficiary. For example, having no difficulty contacting a
provider after regular hours was associated with significantly lower outpatient
expenditures for beneficiaries with high cholesterol and diabetes (n = 635; P =
0.038), but it was associated with significantly higher inpatient expenditures
for beneficiaries with high blood pressure and high cholesterol (n = 1599; P =
0.015), and no significant differences in expenditures in any category for
beneficiaries with high blood pressure and heart disease (n = 1018; P > 0.05 for
all categories). However, average total health care expenditures are largely
unaffected by implementing the PCMH features considered. Understanding how the
needs of Medicare beneficiaries with multiple chronic conditions can be met
through the adoption of the PCMH model is important not only to be able to
provide high-quality care but also to control costs. (Population Health
Management 2016;19:206-211).
PMID- 26440216
TI - Minimal role of base excision repair in TET-induced global DNA demethylation in
HEK293T cells.
AB - Oxidation of 5-methylcytosine by TET family proteins can induce DNA replication
dependent (passive) DNA demethylation and base excision repair (BER)-based
(active) DNA demethylation. The balance of active vs. passive TET-induced
demethylation remains incompletely determined. In the context of large scale DNA
demethylation, active demethylation may require massive induction of the DNA
repair machinery and thus compromise genome stability. To study this issue, we
constructed a tetracycline-controlled TET-induced global DNA demethylation system
in HEK293T cells. Upon TET overexpression, we observed induction of DNA damage
and activation of a DNA damage response; however, BER genes are not upregulated
to promote DNA repair. Depletion of TDG (thymine DNA glycosylase) or APEX1
(apurinic/apyrimidinic endonuclease 1), two key BER enzymes, enhances rather than
impairs global DNA demethylation, which can be explained by stimulated
proliferation. By contrast, growth arrest dramatically blocks TET-induced global
DNA demethylation. Thus, in the context of TET-induction in HEK293T cells, the
DNA replication-dependent passive mechanism functions as the predominant pathway
for global DNA demethylation. In the same context, BER-based active demethylation
is markedly restricted by limited BER upregulation, thus potentially preventing a
disastrous DNA damage response to extensive active DNA demethylation.
PMID- 26440217
TI - Characterization of aggregate/aggresome structures formed by polyhedrin of Bombyx
mori nucleopolyhedrovirus.
AB - Virus infections often lead to formation of aggregates and aggresomes in host
cells. In this study, production of aggregates and aggresomes by the highly
expressed protein polyhedrin of Bombyx mori nucleopolyhedrovirus (BmNPV) at 24 h
postinfection (p.i.) was detected with a fluorescent molecular dye, and verified
by colocalization of polyhedrin with aggresomal markers, GFP-250 and gamma
tubulin. Polyhedrin aggregates showed hallmark characteristics of aggresomes:
formation was microtubule-dependent; they colocalized with heat shock
cognates/proteins of the 70-kDa family (HSC/HSP70s), ubiquitinated proteins and
recruited the mitochondria. Aggregated polyhedrin protein gradually gained its
active conformation accompanying progress of BmNPV infection. At 48 h p.i.
recovered polyhedrin bound directly to Bombyx mori microtubule-associated protein
1-light chain 3 (BmLC3), an autophagosome marker, and was colocalized with BmLC3
to the isolation membrane of autophagosome, implying the involvement of
polyhedrin in cellular autophagy. Inhibition of autophagy by 3-methyladenine (3
MA) dramatically resulted in decrease of polyhedrin expression and polyhedra
particle production. These observations suggested that highly expressed
polyhedrin forms aggregate to get involved in cellular autophagy then play an
important role in polyhedra production.
PMID- 26440218
TI - Inhibition of phagocytic recognition of anti-D opsonized Rh D+ RBC by polymer
mediated immunocamouflage.
AB - The Rh D antigen posed both a significant clinical risk and inventory supply
issue in transfusion medicine. The successful development of the
immunocamouflaged RBC has the potential to address both the risk of acute anti-D
transfusion reactions and to improve D- blood inventory in geographic locations
where D- blood is rare (e.g., China). The immunocamouflage of RBC was mediated by
the covalent grafting of methoxy(polyethylene glycol) to the cell membrane
thereby obscuring the D protein from the immune system. To determine the
potential efficacy of mPEG-D+ RBC in D- recipients, anti-D alloantibodies from
previously alloimmunized individuals were utilized. The effects of polymer chain
size (2-30 kDa) and grafting concentration (0-4 mM) on antibody binding and
erythrophagocytosis were determined using the clinically validated monocyte
monolayer assay (MMA) and flow cytometry. The immunocamouflage of D was polymer
size and grafting concentration dependent as determined using human anti-D
alloantibodies (both pooled [RhoGAM] and single donors). Importantly, the 20 kDa
polymer provided excellent immunocamouflage of D and reached a clinically
significant level of protection, as measured by the MMA, at grafting
concentrations of >=1.5 mM. These findings further support the potential use of
immunocamouflaged RBC to reduce the risk of acute transfusion reactions following
administration of D+ blood to D- recipients in situations where D- units are
unavailable or supply is geographically constrained.
PMID- 26440219
TI - The application of soy isoflavones for subjective symptoms and objective signs of
vaginal atrophy in menopause: A systematic review of randomised controlled
trials.
AB - Vaginal atrophy is a common complaint among many women in their menopause,
presenting with a cluster of symptoms including dryness, itching,
burning/soreness, discharge, irritation and painful intercourse. We searched for
existing pertinent data in three chief registries. Specified time brackets
included 1996-2013 for Medline, 1990-2013 for Scopus and 2013 for Cochrane
Central Register of Controlled Trials (issue 1). Of 110 potentially relevant
publications, 17 and 9 trials (7 on maturation value and 2 on vaginal dryness)
were selected for qualitative and quantitative analysis, respectively. In
general, soy isoflavones seem to improve vaginal symptoms as opposed to control
arms. Soy isoflavones were also shown to be more efficacious in quantitative
analysis, though this was statistically non-significant. Standardised difference
in means of maturation value change was 0.072 (95% confidence interval [CI]: -
0.42 to 0.57), p = 0.777; heterogeneity P = 0.00; I(2) = 85.15%. Difference in
means of vaginal dryness was - 0.204 (95% CI: - 0.28 to - 0.126), p < 0.001;
heterogeneity P = 0.423; I(2) = 0.00. Soy isoflavones may relieve vaginal
symptoms during menopause; nevertheless beneficial effects still remain uncertain
due to possible publication bias or vast heterogeneity of the selected studies.
Further studies with consistency in design as well as statistics are warranted.
PMID- 26440220
TI - Global Gray Water Footprint and Water Pollution Levels Related to Anthropogenic
Nitrogen Loads to Fresh Water.
AB - This is the first global assessment of nitrogen-related water pollution in river
basins with a specification of the pollution by economic sector, and by crop for
the agricultural sector. At a spatial resolution of 5 by 5 arc minute, we
estimate anthropogenic nitrogen (N) loads to freshwater, calculate the resultant
gray water footprints (GWFs), and relate the GWFs per river basin to runoff to
calculate the N-related water pollution level (WPL) per catchment. The
accumulated global GWF related to anthropogenic N loads in the period 2002-2010
was 13*10(12) m3/y. China contributed about 45% to the global total. Three
quarters of the GWF related to N loads came from diffuse sources (agriculture),
23% from domestic point sources and 2% from industrial point sources. Among the
crops, production of cereals had the largest contribution to the N-related GWF
(18%), followed by vegetables (15%) and oil crops (11%). The river basins with
WPL>1 (where the N load exceeds the basin's assimilation capacity), cover about
17% of the global land area, contribute about 9% of the global river discharge,
and provide residence to 48% of the global population.
PMID- 26440221
TI - Soft-tissue and dermal arrangement in the wing of an Early Cretaceous bird:
Implications for the evolution of avian flight.
AB - Despite a wealth of fossils of Mesozoic birds revealing evidence of plumage and
other soft-tissue structures, the epidermal and dermal anatomy of their wing's
patagia remain largely unknown. We describe a distal forelimb of an
enantiornithine bird from the Lower Cretaceous limestones of Las Hoyas, Spain,
which reveals the overall morphology of the integument of the wing and other
connective structures associated with the insertion of flight feathers. The
integumentary anatomy, and myological and arthrological organization of the new
fossil is remarkably similar to that of modern birds, in which a system of small
muscles, tendons and ligaments attaches to the follicles of the remigial feathers
and maintains the functional integrity of the wing during flight. The new fossil
documents the oldest known occurrence of connective tissues in association with
the flight feathers of birds. Furthermore, the presence of an essentially modern
connective arrangement in the wing of enantiornithines supports the
interpretation of these primitive birds as competent fliers.
PMID- 26440222
TI - Gallic Acid: Review of the Methods of Determination and Quantification.
AB - Gallic acid (3,4,5 trihydroxybenzoic acid) is a secondary metabolite present in
most plants. This metabolite is known to exhibit a range of bioactivities
including antioxidant, antimicrobial, anti-inflammatory, and anticancer. There
are various methods to analyze gallic acid including spectrometry,
chromatography, and capillary electrophoresis, among others. They have been
developed to identify and quantify this active ingredient in most biological
matrices. The aim of this article is to review the available information on
analytical methods for gallic acid, as well as presenting the advantages and
limitations of each technique.
PMID- 26440223
TI - 'HIV has a woman's face': vaginal microbicides and a case of ambiguous failure.
AB - The case is a primary unit of knowledge production in the field of HIV research,
yet the work that is done to construct cases often goes unremarked. In this
paper, the case takes centre stage in an analysis of a set of apparent failures
in HIV prevention research, namely a series of clinical trials to test vaginal
microbicides. Returning to the genesis of the microbicide concept in the early
1990s, I examine how the discourse of women's empowerment was linked to HIV
prevention in a way that mobilized a particular vision of the case, which was
both politically and scientifically expedient. Drawing on an in-depth empirical
study of one particular trial, I show the success of the case in mobilizing funds
and interest in the research, as well its success in accounting for the failure
of the pharmaceutical technology. Drawing in alternative scientific accounts of
the failure of microbicides, however, a different version of events is indicated,
in which what can ultimately be said to have failed is not the technology itself,
but the act of casing upon which its testing was founded.
PMID- 26440224
TI - Chemo-, regio-, and stereo-selective perfluoroalkylations by a Grignard complex
with zirconocene.
AB - The synthesis of highly reactive perfluoroalkyl Grignard reagents with early
transition metal zirconocene complexes and their new types of highly chemo-,
regio-, and stereo-selective perfluoroalkylation reactions are reported with
epoxides in particular. The zirconocene complex is advantageous in activating the
perfluoroalkyl Grignard species. The zirconocene.Grignard complexes were
clarified by DOSY. Both (1)H and (19)F DOSY analyses show that the addition of
MAO and dioxane to the mixture of RFMgCl and Cp2ZrCl2 connects Cp2Zr and RFMg to
generate the zirconocene/perfluoroalkyl-Grignard/dioxane complex.
PMID- 26440225
TI - Tunable multiband metasurfaces by moire nanosphere lithography.
AB - Moire nanosphere lithography (MNSL), which features the relative in-plane
rotation between two layers of self-assembled monodisperse nanospheres as masks,
provides a cost-effective approach for creating moire patterns on generic
substrates. In this work, we experimentally and numerically investigate a series
of moire metasurfaces by MNSL. Due to the variety of gradient plasmonic
nanostructures in arrays, single moire metasurfaces can support multiple
localized surface plasmon (LSP) modes with a wide range of resonant wavelengths
from ~600 nm to ~4200 nm. We analyze the origin of the LSP modes based on the
optical spectra and near-field electromagnetic distributions. In addition, we
fabricate and analyze the metasurfaces with high-density nanogap structures.
These nanogap structures support plasmonic gap modes with significant field
enhancements. With their tunable multiband optical responses from visible to near
infrared to mid-infrared regimes, these moire metasurfaces are applicable for
ultrabroadband absorbers, multiband surface-enhanced infrared and Raman
spectroscopy, and broadband single-molecule spectroscopy.
PMID- 26440226
TI - Saponin-enriched sea cucumber extracts exhibit an antiobesity effect through
inhibition of pancreatic lipase activity and upregulation of LXR-beta signaling.
AB - CONTEXT: Sea cucumbers have been consumed as tonic, food, and nutrition
supplements for many years. OBJECTIVE: The objective of this study is to
investigate the antiobesity and lipid-lowering effects of sea cucumber extracts
in in vitro and in vivo models and elucidate the mechanism of action of the
extracts on obesity and dyslipidemia. MATERIALS AND METHODS: The 60% ethanol
extracts from the body walls of 10 different sea cucumbers were investigated for
the inhibition of pancreatic lipase (PL) activity in vitro. The optimal active
extract (SC-3) was further chemically analyzed by LC-MS and UV. And 0.1% and 0.2%
of SC-3 was mixed with a high-fat diet to treat C57/BL6 mice for 6 weeks or 2
weeks as preventive and therapeutic study. The body weight, serum, and liver
lipid profile in the mice were investigated. RESULTS: The crude extract of
Pearsonothuria graeffei Semper (Holothuriidae) inhibited the PL activity by
36.44% of control at 0.5 MUg/mL. SC-3 and echinoside A inhibited PL with an IC50
value at 2.86 MUg/mL and 0.76 MUM. 0.1% of SC-3 reduced the body weight (23.0 +/-
0.62 versus 26.3 +/- 0.76 g), the serum TC (2.46 +/- 0.04 versus 2.83 +/- 0.12
mmol/L), TG (0.19 +/- 0.08 versus 0.40 +/- 0.03 mmo/L), and LDL-c (0.48 +/- 0.02
versus 0.51 +/- 0.02 mmol/L), and liver TC (1.19 +/- 0.17 versus 1.85 +/- 0.13
mmol/mg) and TG (6.18 +/- 0.92 versus 10.87 +/- 0.97 mmol/mg) contents of the
obese C57BL/six mice on a high-fat diet. DISCUSSION AND CONCLUSION: Sea cucumber
may be used for developing antiobesity and antihyperlipidemia drugs.
PMID- 26440228
TI - Ardous journey from IACTA education and research cell to Indian College of
Cardiac Anaesthesia.
PMID- 26440227
TI - Platelet inhibition with ticagrelor versus clopidogrel in Hispanic patients with
stable coronary artery disease with or without diabetes mellitus.
AB - BACKGROUND/PURPOSE: Diabetes mellitus (DM) disproportionately affects Hispanic
patients. DM patients have enhanced platelet reactivity and reduced sensitivity
to clopidogrel. Ticagrelor demonstrated a more rapid onset and greater magnitude
of platelet inhibition than clopidogrel in Hispanic patients with stable coronary
artery disease (CAD). This subgroup analysis examined the onset and level of
platelet inhibition of ticagrelor and clopidogrel in Hispanic patients with DM.
METHODS/MATERIALS: This was a subgroup analysis of a randomized, open-label,
crossover study in which 40 Hispanic patients with stable CAD received ticagrelor
180 mg loading dose (LD)/90 mg twice-daily maintenance dose (MD) then clopidogrel
600 mg LD/75 mg once-daily MD, or vice versa. The primary end point was on
treatment platelet reactivity at 2 hours post-LD using the VerifyNowTM P2Y12
test. RESULTS: 21 patients had DM and 19 were non-diabetic. At 2 hours post-LD,
mean platelet reactivity in the diabetic group was 34.5 PRU with ticagrelor
versus 219.3 PRU with clopidogrel (P<0.001), and in the non-diabetic group was
33.7 PRU with ticagrelor versus 181.0 PRU with clopidogrel (P<0.001). In both
diabetic and non-diabetic subgroups, mean platelet reactivity declined to a
significantly greater extent with ticagrelor than clopidogrel at all time points
evaluated (0.5, 2, and 8 hours post LD and after 7-9 days of MD). Patients were
significantly more likely to have high on-treatment platelet reactivity (>=208
PRU) during treatment with clopidogrel compared with ticagrelor, regardless of
diabetic status. CONCLUSIONS: Among Hispanic patients with stable CAD, ticagrelor
achieves a faster onset and greater magnitude of platelet inhibition compared
with clopidogrel, irrespective of diabetic status.
PMID- 26440229
TI - Optimizing current blood utilization practices in perioperative patients using
the lean team approach.
PMID- 26440230
TI - The increasing importance of percutaneous mechanical circulatory assist device
therapy in heart failure management.
AB - INTRODUCTION: Advances in medical and surgical care have made it possible for an
increasing number of patients with Congenital Heart disease (CHD) to live into
adulthood. Transposition of the great vessels (TGV) is the most common cyanotic
congenital cardiac disease where the right ventricle serves as systemic
ventricle. It is not uncommon for these patients to have systemic ventricular
failure requiring transplantation. STUDY DESIGN: Hemodynamic decompensation in
these patients can be swift and difficult to manage. Increasingly percutaneous
LVAD's such as the Impella (Abiomed, Mass, USA) are gaining popularity in these
situations owing to their relative ease of placement, both in and outside of the
operating room. CONCLUSION: In this paper we demonstrate that Impella (IMP) CP
placement through the axillary artery approach shows to be suitable option for
short term cardiac support and improvement of end organ perfusion in anticipation
of cardiac transplantation.
PMID- 26440231
TI - An analysis of the factors influencing pulmonary artery catheter placement in
anesthetized patients.
AB - BACKGROUND: Pulmonary artery catheters are usually placed by resident
anesthesiologists with pressure wave monitoring from educational point of view.
In some cases, the placement needs longer time or is difficult only by observing
the pressure waves. AIMS: We sought to examine the time required for the catheter
placement in adult patients and determine factors influencing the placement.
SETTINGS AND DESIGNS: Prospective, observational, cohort study. METHODS: We
examined the time required for the catheter placement. If the catheter is placed
in longer than 5 min, this could be a difficult placement. We examined the effect
of the patient's age, body mass index, cardiothoracic ratio (CTR) and tricuspid
regurgitation, left ventricular ejection fraction (LVEF) and training duration of
a resident on the difficult catheter placement. Next, we excluded the difficult
cases from the analysis and examined the effect of these factors on the placement
time. STATISTICAL ANALYSIS: The data were analyzed by logistic regression
analysis to assess factors for the difficult catheter placement and multiple
linear regression analysis to evaluate the factors to increase the placement time
after univariate analyses. RESULTS: The difficult placement occurred in 6
patients (5.7%). The analysis showed that LVEF was a significant factor to hinder
the catheter placement (P = 0.02) while CTR was a significant factor to increase
the placement time (P = 0.002). CONCLUSION: LVEF and CTRs are significant factors
to be associated with the difficult catheter placement and to increase the
placement time, respectively.
PMID- 26440232
TI - Exertional-induced bronchoconstriction: comparison between cardiopulmonary
exercise test and methacholine challenging test.
AB - INTRODUCTION: Exertional-induced bronchoconstriction is a condition in which the
physical activity causes constriction of airways in patients with airway hyper-
responsiveness. In this study, we tried to study and evaluate any relationship
between the findings of cardiopulmonary exercise testing (CPET) and the response
to methacholine challenge test (MCT) in patients with dyspnea after activity.
MATERIALS AND METHODS: Thirty patients with complaints of dyspnea following
activity referred to "Lung Clinic" of Baqiyatallah Hospital but not suffering
from asthma were entered into the study. The subjects were excluded from the
study if: Suffering from any other pulmonary diseases, smoking more than 1
cigarette a week in the last year, having a history of smoking more than 10
packets of cigarettes/year, having respiratory infection in the past 4 weeks,
having abnormal chest X-ray or electrocardiogram, and cannot discontinue the use
of medicines interfering with bronchial provocation. Baseline spirometry was
performed for all the patients, and the values of forced expiratory volume in 1
second (FEV1), forced vital capacity (FVC), and FEV/FVC were recorded. The MCT
and then the CPET were performed on all patients. RESULTS: The mean VO 2 (volume
oxygen) in patients with positive methacholine test (20.45 mL/kg/min) was
significantly lower than patients with negative MCT (28.69 mL/kg/min) (P =
0.000). Respiratory rates per minute (RR) and minute ventilation in the group
with positive MCT (38.85 and 1.636 L) were significantly lower than the group
with negative methacholine test (46.78 and 2.114 L) (P < 0.05). Also, the O 2
pulse rate in the group with negative methacholine test (116.27 mL/beat) was
significantly higher than the group with positive methacholine test (84.26
mL/beat) (P < 0.001). CONCLUSION: Pulmonary response to exercise in patients with
positive methacholine test is insufficient. The dead space ventilation in these
patients has increased. Also, dynamic hyperinflation in patients with positive
methacholine test causes the reduced stroke volume and O 2 pulse in these
patients.
PMID- 26440233
TI - Impact comparison of ketamine and sodium thiopental on anesthesia during
electroconvulsive therapy in major depression patients with drug-resistant; a
double-blind randomized clinical trial.
AB - BACKGROUND: Electroconvulsive therapy (ECT) is one of the available and the most
effective therapies for the treatment of resistant depression. Considering the
crucial role of seizure duration on therapeutic response in patients treated with
ECT, this study aimed to compare the effect of ketamine and sodium thiopental
anesthesia during ECT for treatment of patients with drug-resistant major
depression (DRMD). MATERIALS AND METHODS: In a double-blind randomized clinical
trial, 160 patients with DRMD were selected consequently and were assigned
randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5
mg/kg. The seizure duration, recovery time, and the side effects of anesthesia
were evaluated after 1-h after anesthesia. Data of recovery time and complication
collected in 2 nd , 4 th , 6 th , and 8 th ECT. Depression was assessed by
Hamilton depression scale. RESULTS: The results indicated that ketamine and
sodium thiopental had a significant effect on the reduction of depression scores
in patients with DRMD (P < 0.05). Complications such as a headache, nausea, pain
at the injection site, short-term delirium, and long-term delirium were higher in
ketamine group (P > 0.05). But ketamine was more effective in improvement of
depression score and increasing systolic and diastolic blood pressure (P < 0.05).
The mean of seizure duration showed a decreasing trend and was significant
between two study groups (P < 0.05). CONCLUSION: Anesthesia induced by ketamine
during ECT therapy increased blood pressure and seizure duration. Therefore, due
to lower medical complication and attack rate of seizure, ketamine is an
appropriate option for anesthesia with ECT in patients with DRMD.
PMID- 26440234
TI - Where does the pulmonary artery catheter float: transesophageal echocardiography
evaluation.
AB - BACKGROUND: Pulmonary artery (PA) catheter provides a variety of cardiac and
hemodynamic parameters. In majority of the patients, the catheter tends to float
in the right pulmonary artery (RPA) than the left pulmonary artery (LPA). We
evaluated the location of PA catheter with the help of transesophageal
echocardiography (TEE) to know the incidence of its localization. Three views
were utilized for this purpose; midesophageal ascending aorta (AA) short-axis
view, modified mid esophageal aortic valve long-axis view, and modified bicaval
view. METHODS: We enrolled 135 patients undergoing elective cardiac surgery where
both the PA catheter and TEE were to be used; for this prospective observational
study. PA catheter was visualized by TEE in the above mentioned views and the
degree of clarity of visualization by three views was also noted. Position of the
PA catheter was further confirmed by a postoperative chest radiograph. RESULTS:
One patient was excluded from the data analysis. PA catheter was visualized in
RPA in 129 patients (96%) and in LPA in 4 patients (3%). In 1 patient, the
catheter was visualized in main PA in the chest radiograph. The midesophageal AA
short-axis, modified aortic valve long-axis, and modified bicaval view provided
good visualization in 51.45%, 57.4%, and 62.3% patients respectively. Taken
together, PA catheter visualization was good in 128 (95.5%) patients. CONCLUSION:
We conclude that the PA catheter has a high probability of entering the RPA as
compared to LPA (96% vs. 3%) and TEE provides good visualization of the catheter
in RPA.
PMID- 26440235
TI - Anti-inflammatory effects of propofol during cardiopulmonary bypass: a pilot
study.
AB - INTRODUCTION: Propofol has been suggested as a useful adjunct to cardiopulmonary
bypass (CPB) because of its potential protective effect on the heart mediated by
a decrease in ischemia-reperfusion injury and inflammation at clinically relevant
concentrations. In view of these potentially protective properties, which
modulate many of the deleterious mechanism of inflammation attributable to
reperfusion injury and CPB, we sought to determine whether starting a low dose of
propofol infusion at the beginning of CPB would decrease inflammation as measured
by pro-inflammatory markers. MATERIALS AND METHODS: We enrolled 24 patients
undergoing elective coronary artery bypass graft (CABG). The study group received
propofol at rate of 120 mcg/kg/min immediately after starting CPB and was
maintained throughout the surgery and for the following 6 hours in the intensive
care unit (ICU). The control group received propofol dose of 30-50 mcg/kg/min
which was started at the time of chest closure with wires and continued for the
next 6 hours in the ICU. Interleukins (IL) -6, -8 and -10 and tumor necrosis
factor alpha (TNFalpha) were assayed. RESULT: The most significant difference was
in the level of IL-6 which had a P value of less than 0.06. Starting a low dose
propofol early during the CPB was not associated with significant hemodynamic
instability in comparison with the control group. CONCLUSION: Our study shows
that propofol may be suitable as an anti-inflammatory adjunct for patients
undergoing CABG.
PMID- 26440236
TI - Comparison of the effects of inhalational anesthesia with desflurane and total
intravenous anesthesia on cardiac biomarkers after aortic valve replacement.
AB - OBJECTIVE (S): The aim of this study was to compare the effects of using
inhalational anesthesia with desflurane with that of a total intravenous (iv)
anesthetic technique using midazolam-fentanyl-propofol on the release of cardiac
biomarkers after aortic valve replacement (AVR) for aortic stenosis (AS). The
specific objectives included (a) determination of the levels of ischemia-modified
albumin (IMA) and cardiac troponin I (cTnI) as markers of myocardial injury, (b)
effect on mortality, morbidity, duration of mechanical ventilation, length of
Intensive Care Unit (ICU) and hospital stay, incidence of arrhythmias, pacing,
cardioversion, urine output, and serum creatinine. Methodology and Design:
Prospective randomized clinical study. SETTING: Operation room of a cardiac
surgery center of a tertiary teaching hospital. PARTICIPANTS: Seventy-six
patients in New York Heart Association classification II to III presenting
electively for AVR for severe symptomatic AS. INTERVENTIONS: Patients included in
the study were randomized into two groups and subjected to either a desflurane
fentanyl based technique or total IV anesthesia (TIVA). Blood samples were drawn
at preordained intervals to determine the levels of IMA, cTnI, and serum
creatinine. MEASUREMENTS AND MAIN RESULTS: The IMA and cTnI levels were not found
to be significantly different between both the study groups. Patients in the
desflurane group were found to had significantly lower ICU and hospital stays and
duration of postoperative mechanical ventilation as compared to those in the TIVA
group. There was no difference found in mean heart rate, urine output, serum
creatinine, incidence of arrhythmias, need for cardioversion, and 30-day
mortality between both groups. The patients in the TIVA group had higher mean
arterial pressures on weaning off cardiopulmonary bypass as well as
postoperatively in the ICU and recorded lower inotrope usage. CONCLUSION: The
result of our study remains ambiguous regarding the overall protective effect of
desflurane in patients undergoing AVR although some benefit in terms of shorter
duration of postoperative mechanical ventilation, ICU and hospital stays, as well
as cTnI, were seen. However, no difference in overall outcome could be clearly
established between patients who received desflurane and those that were managed
solely with IV anesthetic technique using propofol.
PMID- 26440237
TI - Does intravenous sildenafil clinically ameliorate pulmonary hypertension during
perioperative management of congenital heart diseases in children? - a
prospective randomized study.
AB - BACKGROUND: Pulmonary hypertension (PHT), if present, can be a significant cause
of increased morbidity and mortality in children undergoing surgery for
congenital heart diseases (CHD). Various techniques and drugs have been used
perioperatively to alleviate the effects of PHT. Intravenous (IV) sildenafil is
one of them and not many studies validate its clinical use. AIMS AND OBJECTIVES:
To compare perioperative PaO 2 - FiO 2 ratio peak filling rate (PFR), systolic
pulmonary artery pressure (PAP) - systolic aortic pressure (AoP) ratio,
extubation time, and Intensive Care Unit (ICU) stay between two groups of
children when one of them is administered IV sildenafil perioperatively during
surgery for CHDs. MATERIALS AND METHODS: Patients with ventricular septal defects
and proven PHT, <14 years of age, all American Society of Anesthesiologists
physical status III, undergoing cardiac surgery, were enrolled into two groups -
Group S (IV sildenafil) and Group C (control) - over a period of 14 months,
starting from October 2013. Independent t-test and Mann-Whitney U-test were used
to compare the various parameters between two groups. RESULTS: PFR was higher
throughout, perioperatively, in Group S. PAP/AoP was 0.3 and 0.4 in Group S and
Group C, respectively. In Group S, mean group extubation time was 7 +/- 7.34 h,
whereas in Group C it was 22.1 +/- 10.6. Postoperative ICU stay in Group S and
Group C were 42.3 +/- 8.8 h and 64.4 +/- 15.9 h, respectively. CONCLUSION: IV
sildenafil, when used perioperatively, in children with CHD having PHT undergoing
corrective surgery, improves not only PaO 2 - FiO 2 ratio and PAP - AoP ratio but
also reduces extubation time and postoperative ICU stay.
PMID- 26440238
TI - Perioperative venous thromboembolic disease and the emerging role of the novel
oral anticoagulants: an analysis of the implications for perioperative
management.
AB - Venous thromboembolism includes 2 inter-related conditions: Deep venous
thrombosis and pulmonary embolism. Heparin and low-molecular-weight heparin
followed by oral anticoagulation with vitamin K agonists is the first line and
current accepted standard therapy with good efficacy. However, this therapeutic
strategy has many limitations including the significant risk of bleeding and
drug, food and disease interactions that require frequent monitoring. Dabigatran,
rivaroxaban, apixaban, and edoxaban are the novel oral anticoagulants that are
available for use in stroke prevention in atrial fibrillation and for the
treatment and prevention of venous thromboembolism (HYPERLINK?l "1). Recent
prospective randomized trials comparing the NOACs with warfarin have shown
similar efficacy between the treatment strategies but fewer bleeding episodes
with the NOACs. This paper presents an evidence-based review describing the
efficacy and safety of the new anticoagulants compared to warfarin.
PMID- 26440239
TI - Percutaneous and minimally invasive approaches to mitral valve repair for severe
mitral regurgitation-new devices and emerging outcomes.
AB - Mitral valve disease is common in the United States and around the world, and if
left untreated, increases cardiovascular morbidity and mortality. Mitral valve
repair is technically more demanding than mitral valve replacement. Mitral valve
repair should be considered the first line of treatment for mitral regurgitation
in younger patients, mitral valve prolapse, annular dilatation, and with
structural damage to the valve. Several minimally invasive percutaneous treatment
options for mitral valve repair are available that are not restricted to
conventional surgical approaches, and may be better received by patients. A
useful classification system of these approaches proposed by Chiam and Ruiz is
based on anatomic targets and device action upon the leaflets, annulus, chordae,
and left ventricle. Future directions of minimally invasive techniques will
include improving the safety profile through patient selection and risk
stratification, improvement of current imaging and techniques, and
multidisciplinary education.
PMID- 26440240
TI - Intraoperative aortic dissection.
AB - Intraoperative aortic dissection is a rare but fatal complication of open heart
surgery. By recognizing the population at risk and by using a gentle operative
technique in such patients, the surgeon can usually avoid iatrogenic injury to
the aorta. Intraoperative transesophageal echocardiography and epiaortic scanning
are invaluable for prompt diagnosis and determination of the extent of the
injury. Prevention lies in the strict control of blood pressure during
cannulation/decannulation, construction of proximal anastomosis, or in avoiding
manipulation of the aorta in high-risk patients. Immediate repair using
interposition graft or Dacron patch graft is warranted to reduce the high
mortality associated with this complication.
PMID- 26440241
TI - Pharmacologic agents for acute hemodynamic instability: recent advances in the
management of perioperative shock- a systematic review.
AB - Despite the growing body of evidence evaluating the efficacy of vasoactive agents
in the management of hemodynamic instability and circulatory shock, it appears no
agent is superior. This is becoming increasingly accepted as current guidelines
are moving away from detailed algorithms for the management of shock, and instead
succinctly state that vasoactive agents should be individualized and guided by
invasive hemodynamic monitoring. This extends to the perioperative period, where
vasoactive agent selection and use may still be left to the discretion of the
treating physician with a goal-directed approach, consisting of close hemodynamic
monitoring and administration of the lowest effective dose to achieve the
hemodynamic goals. Successful therapy depends on the ability to rapidly diagnose
the etiology of circulatory shock and thoroughly understand its pathophysiology
as well as the pharmacology of vasoactive agents. This review focuses on the
physiology and resuscitation goals in perioperative shock, as well as the
pharmacology and recent advances in vasoactive agent use in its management.
PMID- 26440243
TI - Perioperative atrial fibrillation: a systematic review of evolving therapeutic
options in pharmacologic and procedural management.
AB - Given the high incidence of atrial fibrillation (AF) in the surgical population
and the associated morbidity, physicians managing these complicated patients in
the perioperative period need to be aware of the new and emerging trends in its
therapy. The cornerstones of AF management have always been rate/rhythm control
as well as anticoagulation. Restoration of sinus rhythm remains the fundamental
philosophy as it maintains the atrial contribution to cardiac output and improves
ventricular function. The recent years have seen a dramatic increase in the
number of randomized AF trials that have made significant advances to our
understanding of both pharmacologic and procedural management, from the
introduction of the new generation of oral anticoagulants (NOAC's) to catheter
approaches for AF ablation. This paper will summarize the newest data that will
affect the perioperative management of these patients.
PMID- 26440244
TI - Large left ventricular pseudoaneurysm and spontaneous recanalized coronaries.
AB - 35 year old with ruptured lateral wall of Left ventricle (LV) resulting in large
pseudo aneurysm contained within the pericardium [Figure 1]. There was free flow
of blood between the LV and pseudoaneurysm .He underwent endoventricular patch
plasty of the defect after opening the wall of aneurysm [Figure 2].
PMID- 26440245
TI - Capnothorax induced subclavian artery compression.
PMID- 26440246
TI - Noninvasive removal of a knotted pulmonary artery catheter.
PMID- 26440242
TI - Mechanisms of oxidative stress and myocardial protection during open-heart
surgery.
AB - Cold heart protection via cardioplegia administration, limits the amount of
oxygen demand. Systemic normothermia with warm cardioplegia was introduced due to
the abundance of detrimental effects of hypothermia. A temperature of 32-33
degrees C in combination with tepid blood cardioplegia of the same temperature
appears to be protective enough for both; heart and brain. Reduction of nitric
oxide (NO) concentration is in part responsible for myocardial injury after the
cardioplegic cardiac arrest. Restoration of NO balance with exogenous NO
supplementation has been shown useful to prevent inflammation and apoptosis. In
this article, we discuss the "deleterious" effects of the oxidative stress of the
extracorporeal circulation and the up-to-date theories of "ideal'' myocardial
protection.
PMID- 26440247
TI - Role of phenoxybenzamine in perioperative clinical practice.
PMID- 26440248
TI - Echocardiographic detection of free-floating thrombus in left ventricle during
coronary artery bypass grafting.
AB - We report an incident of detection of a free-floating thrombus in the left
ventricle (LV) using intraoperative two-dimensional (2D) and three-dimensional
(3D) transesophageal echocardiography (TEE) during proximal coronary artery
bypass graft anastomosis. A 58-year-old man presented to us with a 6-month
history of chest pain without any history suggestive of myocardial infarction or
transient ischemic attacks. His preoperative echocardiography revealed the
systolic dysfunction of LV, mild hypokinesia of basal and mid-anterior wall, and
the absence of an aneurysm. He was scheduled for on-pump coronary artery bypass
surgery. On intraoperative TEE before establishing cardiopulmonary bypass (CPB),
a small immobile mass was found attached to LV apical area. After completion of
distal coronary artery grafting, when the aortic cross-clamp was removed, the
heart was filled partially and beating spontaneously. TEE examination using 2D
mode revealed a free-floating mass in the LV, which was suspected to be a
thrombus. Additional navigation using biplane and 3D modes confirmed the presence
of the thrombus and distinguished it from papillary muscles and artifact. The
surgeon opened the left atrium after re-establishing electromechanical quiescence
and removed a thrombus measuring 1.5 cm Chi 1 cm from the LV. The LV mass in the
apical region was no longer seen after discontinuation of CPB. Accurate TEE
detection and timely removal of the thrombus averted disastrous embolic
complications. Intraoperative 2D and recent biplane and 3D echocardiography modes
are useful monitoring tools during the conduct of CPB.
PMID- 26440249
TI - Transvalvular mitral regurgitation following mitral valve replacement a
diagnostic dilemma.
AB - After mitral valve replacement with a prosthetic valve, the valve should be
competent and there should not be any residual prosthetic valve regurgitation.
Transvalvular residual prosthetic valve regurgitation are difficult to diagnose
and quantify. we are reporting interesting TEE images as a diagnostic dilemma in
a case of transvalvular mitral regurgitation following mitral valve replacement
secondary to entrapment of sub-valvular apparatus in a Chitra mechanical heart
valve.
PMID- 26440250
TI - Which valve is which?
AB - A 25-year-old man presented with a history of breathlessness for the past 2
years. He had a history of operation for Tetralogy of Fallot at the age of 5
years and history suggestive of Rheumatic fever at the age of 7 years. On
echocardiographic examination, all his heart valves were severely regurgitating.
Morphologically, all the valves were irreparable. The ejection fraction was 35%.
He underwent quadruple valve replacement. The aortic and mitral valves were
replaced by metallic valve and the tricuspid and pulmonary by tissue valve.
PMID- 26440251
TI - Case report of fatal complication of superior vena cava tear from balloon
dilatation of iatrogenic superior vena cava narrowing.
AB - The treatment options for superior vena cava (SVC) obstruction depends on the
cause and severity of SVC narrowing. It ranges from conservative medical
management to more elaborate endovascular and surgical repair of obstruction.
There has always been a concern regarding the possibility of rupture of SVC
during balloon dilatation, if the obstruction is secondary to the surgical cause.
Very few cases are reported in the literature. We report a case of fatal
complication of SVC tear in a 2-month-old child who had iatrogenic SVC narrowing.
PMID- 26440252
TI - Role of transesophageal echocardiography: a rare case of acute left atrial free
wall dissection.
AB - Transesophageal echocardiography (TEE) has been used routinely in the diagnosis
and follow-up of cardiac cases. Left atrial dissection (LAd), an exceedingly rare
complication of cardiac surgery, is most commonly associated with mitral valve
surgery. A case of LAd is presented, and the pathology was accurately defined and
immediately diagnosed using intraoperative TEE. This case highlights the
importance of prompt diagnosis of LAd using intraoperative TEE, and a second
cardiac surgery was avoided.
PMID- 26440253
TI - Airway compromise during central venous cannulation in an undiagnosed tubercular
retropharyngeal abscess: a case report.
AB - Central venous cannulation is often associated with complications during
insertion even by expert's hand and with the aid of ultrasound. We encountered a
patient for central line insertion through the right internal jugular vein having
a retropharyngeal abscess of tubercular origin. We accidentally punctured the
abscess cavity leading to increased respiratory distress and subsequent need of
intubation to the patient. This kind of complication during central line
insertion has never been reported before. We intend to report such a case to
alert everyone about the grave complications it can lead to and the methods to
minimize them in the times ahead.
PMID- 26440254
TI - Unusual cause of hypoxemia after automatic implantable cardioverter
defibrillatorleads extraction.
AB - The indication of pacemaker/AICD removal are numerous. Serious complication can
occur during their removal, severe tricuspid regurgitation is one of the
complication. The occurrence of PFO is not uncommon among adult population.
Shunting across PFO in most circumstance is negligible, but in some necessitates
closure due to hypoxemia. We report a case of 62 year old man, while undergoing
AICD removal, had an emergency sternotomy for cardiac tamponade. Postoperatively,
he experienced profound hypoxemia refractory to oxygen therapy. Transthoracic
Echocardiogram was performed to rule out intracardiac shunts at an early stage,
but it was difficult to obtain an good imaging windows poststernotomy. A small
pulmonary emboli was noted on CTPA, but was not sufficient to account for the
level of hypoxemia and did not resolve with anticoagulation. Transesophageal
echocardiogram showed flail septal tricuspid valve with severe TR and
bidirectional shunt through large PFO. Patient was posted for surgery, tricuspid
valve was replaced and PFO surgically closed. Subsequently, patient recovered
well ad was discharged to home. Cause of hypoxemia might be due to respiratory or
cardiac dysfunction. But for hypoxemia refractory to oxygen therapy,
transoesophageal echocardiogram should be always considered and performed early
as an diagnostic tool in post cardiac surgical patients.
PMID- 26440255
TI - Challenges of valve surgeries in post-renal transplant patients.
AB - Renal transplantation remains a mainstay of therapy for the end-stage renal
disease. Cardiac disease has a high prevalence in this patient population.
Cardiovascular disease remains the leading cause of death among kidney
transplantation patients. The cardiac disease accounts for 43% of all-cause
mortality among dialysis patients and for ~38% of all-cause mortality after
transplantation. In this article, we review the factors and outcomes associated
with valve surgeries in renal transplant recipients and evaluate the strategy for
open heart surgery after renal transplantation performed.
PMID- 26440256
TI - Selective use of superficial temporal artery cannulation in infants undergoing
cardiac surgery.
AB - Arterial cannulation is routinely performed in children undergoing cardiac
surgery to aid the intraoperative and intensive care management. Most commonly
cannulated peripheral site in children is radial artery, and alternatives include
posterior tibial, dorsalis pedis, and rarely superficial temporal artery (STA).
Two specific situations in cardiac surgery where STA cannulation and monitoring
was useful during the surgical procedure are reported. To our knowledge, such
selective use of STA pressure monitoring has not been reported in the literature
previously. Our experience suggests that STA monitoring can be useful and
reliable during repair of coarctation of aorta or administration of anterograde
cerebral perfusion in patients having associated aberrant origin of the right
subclavian artery.
PMID- 26440258
TI - An efficient algorithm for calculating the exact Hausdorff distance.
AB - The Hausdorff distance (HD) between two point sets is a commonly used
dissimilarity measure for comparing point sets and image segmentations.
Especially when very large point sets are compared using the HD, for example when
evaluating magnetic resonance volume segmentations, or when the underlying
applications are based on time critical tasks, like motion detection, then the
computational complexity of HD algorithms becomes an important issue. In this
paper we propose a novel efficient algorithm for computing the exact Hausdorff
distance. In a runtime analysis, the proposed algorithm is demonstrated to have
nearly-linear complexity. Furthermore, it has efficient performance for large
point set sizes as well as for large grid size; performs equally for sparse and
dense point sets; and finally it is general without restrictions on the
characteristics of the point set. The proposed algorithm is tested against the HD
algorithm of the widely used national library of medicine insight segmentation
and registration toolkit (ITK) using magnetic resonance volumes with extremely
large size. The proposed algorithm outperforms the ITK HD algorithm both in speed
and memory required. In an experiment using trajectories from a road network, the
proposed algorithm significantly outperforms an HD algorithm based on R-Trees.
PMID- 26440257
TI - Lipomatous hypertrophy of the interatrial septum and fibrosing mediastinal
lymphadenopathy causing superior vena cava obstruction.
AB - Lipomatous hypertrophy of the interatrial septum (LHIS) is an uncommon cause of
superior vena cava syndrome (SVCS). Fibrosing mediastinal lymphadenopathy is
another cause of SVCS. We present a 65-year-old female patient with a history of
tuberculosis (TB) and the coexistence of LHIS and fibrosing mediastinitis due to
TB of the lung. Fibrosing or sclerosing mediastinitis is a rare entity with few
cases published in the western literature. She presented with mild symptomatology
of SVCS and she underwent on transthoracic and transesophageal echocardiography,
computed tomography scan, magnetic resonance imaging, and venography. Due to the
development of an abundant collateral venous system seen on venography and her
negation for any treatment, she did not undergo yet on any intervention. To our
knowledge, this is the first case reported in the international bibliography in
which LHIS and sclerosing lymphadenopathy are simultaneously diagnosed in the
same patient.
PMID- 26440259
TI - Difference subspace and its generalization for subspace-based methods.
AB - Subspace-based methods are known to provide a practical solution for image set
based object recognition. Based on the insight that local shape differences
between objects offer a sensitive cue for recognition, this paper addresses the
problem of extracting a subspace representing the difference components between
class subspaces generated from each set of object images independently of each
other. We first introduce the difference subspace (DS), a novel geometric concept
between two subspaces as an extension of a difference vector between two vectors,
and describe its effectiveness in analyzing shape differences. We then generalize
it to the generalized difference subspace (GDS) for multi-class subspaces, and
show the benefit of applying this to subspace and mutual subspace methods, in
terms of recognition capability. Furthermore, we extend these methods to kernel
DS (KDS) and kernel GDS (KGDS) by a nonlinear kernel mapping to deal with cases
involving larger changes in viewing direction. In summary, the contributions of
this paper are as follows: 1) a DS/KDS between two class subspaces characterizes
shape differences between the two respectively corresponding objects, 2) the
projection of an input vector onto a DS/KDS realizes selective visualization of
shape differences between objects, and 3) the projection of an input vector or
subspace onto a GDS/KGDS is extremely effective at extracting differences between
multiple subspaces, and therefore improves object recognition performance. We
demonstrate validity through shape analysis on synthetic and real images of 3D
objects as well as extensive comparison of performance on classification tests
with several related methods; we study the performance in face image
classification on the Yale face database B+ and the CMU Multi-PIE database, and
hand shape classification of multi-view images.
PMID- 26440260
TI - Fusion of range and stereo data for high-resolution scene-modeling.
AB - This paper addresses the problem of range-stereo fusion, for the construction of
high-resolution depth maps. In particular, we combine low-resolution depth data
with high-resolution stereo data, in a maximum a posteriori (MAP) formulation.
Unlike existing schemes that build on MRF optimizers, we infer the disparity map
from a series of local energy minimization problems that are solved
hierarchically, by growing sparse initial disparities obtained from the depth
data. The accuracy of the method is not compromised, owing to three properties of
the data-term in the energy function. First, it incorporates a new correlation
function that is capable of providing refined correlations and disparities, via
subpixel correction. Second, the correlation scores rely on an adaptive cost
aggregation step, based on the depth data. Third, the stereo and depth
likelihoods are adaptively fused, based on the scene texture and camera geometry.
These properties lead to a more selective growing process which, unlike previous
seed-growing methods, avoids the tendency to propagate incorrect disparities. The
proposed method gives rise to an intrinsically efficient algorithm, which runs at
3FPS on 2.0 MP images on a standard desktop computer. The strong performance of
the new method is established both by quantitative comparisons with state-of-the
art methods, and by qualitative comparisons using real depth-stereo data-sets.
PMID- 26440261
TI - Geometric change detection in urban environments using images.
AB - We propose a method to detect changes in the geometry of a city using panoramic
images captured by a car driving around the city. The proposed method can be used
to significantly optimize the process of updating the 3D model of an urban
environment that is changing over time, by restricting this process to only those
areas where changes are detected. With this application in mind, we designed our
algorithm to specifically detect only structural changes in the environment,
ignoring any changes in its appearance, and ignoring also all the changes which
are not relevant for update purposes such as cars, people etc. The approach also
accounts for the challenges involved in a large scale application of change
detection, such as inaccuracies in the input geometry, errors in the geo-location
data of the images as well as the limited amount of information due to sparse
imagery. We evaluated our approach on a small scale setup using high resolution,
densely captured images and a large scale setup covering an entire city using
instead the more realistic scenario of low resolution, sparsely captured images.
A quantitative evaluation was also conducted for the large scale setup consisting
of 14,000 images.
PMID- 26440262
TI - Laplacian scale-space behavior of planar curve corners.
AB - Scale-space behavior of corners is important for developing an efficient corner
detection algorithm. In this paper, we analyze the scale-space behavior with the
Laplacian of Gaussian (LoG) operator on a planar curve which constructs Laplacian
Scale Space (LSS). The analytical expression of a Laplacian Scale-Space map (LSS
map) is obtained, demonstrating the Laplacian Scale-Space behavior of the planar
curve corners, based on a newly defined unified corner model. With this formula,
some Laplacian Scale-Space behavior is summarized. Although LSS demonstrates some
similarities to Curvature Scale Space (CSS), there are still some differences.
First, no new extreme points are generated in the LSS. Second, the behavior of
different cases of a corner model is consistent and simple. This makes it easy to
trace the corner in a scale space. At last, the behavior of LSS is verified in an
experiment on a digital curve.
PMID- 26440263
TI - Learning shared, discriminative, and compact representations for visual
recognition.
AB - Dictionary-based and part-based methods are among the most popular approaches to
visual recognition. In both methods, a mid-level representation is built on top
of low-level image descriptors and high-level classifiers are trained on top of
the mid-level representation. While earlier methods built the mid-level
representation without supervision, there is currently great interest in learning
both representations jointly to make the mid-level representation more
discriminative. In this work we propose a new approach to visual recognition that
jointly learns a shared, discriminative, and compact mid-level representation and
a compact high-level representation. By using a structured output learning
framework, our approach directly handles the multiclass case at both levels of
abstraction. Moreover, by using a group-sparse prior in the structured output
learning framework, our approach encourages sharing of visual words and thus
reduces the number of words used to represent each class. We test our proposed
method on several popular benchmarks. Our results show that, by jointly learning
mid- and high-level representations, and fostering the sharing of discriminative
visual words among target classes, we are able to achieve state-of-the-art
recognition performance using far less visual words than previous approaches.
PMID- 26440264
TI - Multi-view and 3D deformable part models.
AB - As objects are inherently 3D, they have been modeled in 3D in the early days of
computer vision. Due to the ambiguities arising from mapping 2D features to 3D
models, 3D object representations have been neglected and 2D feature-based models
are the predominant paradigm in object detection nowadays. While such models have
achieved outstanding bounding box detection performance, they come with limited
expressiveness, as they are clearly limited in their capability of reasoning
about 3D shape or viewpoints. In this work, we bring the worlds of 3D and 2D
object representations closer, by building an object detector which leverages the
expressive power of 3D object representations while at the same time can be
robustly matched to image evidence. To that end, we gradually extend the
successful deformable part model [1] to include viewpoint information and part
level 3D geometry information, resulting in several different models with
different level of expressiveness. We end up with a 3D object model, consisting
of multiple object parts represented in 3D and a continuous appearance model. We
experimentally verify that our models, while providing richer object hypotheses
than the 2D object models, provide consistently better joint object localization
and viewpoint estimation than the state-of-the-art multi-view and 3D object
detectors on various benchmarks (KITTI [2] , 3D object classes [3] , Pascal3D+
[4] , Pascal VOC 2007 [5] , EPFL multi-view cars[6] ).
PMID- 26440266
TI - Probabilistic ToF and stereo data fusion based on mixed pixels measurement
models.
AB - This paper proposes a method for fusing data acquired by a ToF camera and a
stereo pair based on a model for depth measurement by ToF cameras which accounts
also for depth discontinuity artifacts due to the mixed pixel effect. Such model
is exploited within both a ML and a MAP-MRF frameworks for ToF and stereo data
fusion. The proposed MAP-MRF framework is characterized by site-dependent range
values, a rather important feature since it can be used both to improve the
accuracy and to decrease the computational complexity of standard MAP-MRF
approaches. This paper, in order to optimize the site dependent global cost
function characteristic of the proposed MAP-MRF approach, also introduces an
extension to Loopy Belief Propagation which can be used in other contexts.
Experimental data validate the proposed ToF measurements model and the
effectiveness of the proposed fusion techniques.
PMID- 26440265
TI - Optimal mass transport for shape matching and comparison.
AB - Surface based 3D shape analysis plays a fundamental role in computer vision and
medical imaging. This work proposes to use optimal mass transport map for shape
matching and comparison, focusing on two important applications including surface
registration and shape space. The computation of the optimal mass transport map
is based on Monge-Brenier theory, in comparison to the conventional method based
on Monge-Kantorovich theory, this method significantly improves the efficiency by
reducing computational complexity from O(n(2)) to O(n) . For surface registration
problem, one commonly used approach is to use conformal map to convert the shapes
into some canonical space. Although conformal mappings have small angle
distortions, they may introduce large area distortions which are likely to cause
numerical instability thus resulting failures of shape analysis. This work
proposes to compose the conformal map with the optimal mass transport map to get
the unique area-preserving map, which is intrinsic to the Riemannian metric,
unique, and diffeomorphic. For shape space study, this work introduces a novel
Riemannian framework, Conformal Wasserstein Shape Space, by combing conformal
geometry and optimal mass transport theory. In our work, all metric surfaces with
the disk topology are mapped to the unit planar disk by a conformal mapping,
which pushes the area element on the surface to a probability measure on the
disk. The optimal mass transport provides a map from the shape space of all
topological disks with metrics to the Wasserstein space of the disk and the
pullback Wasserstein metric equips the shape space with a Riemannian metric. We
validate our work by numerous experiments and comparisons with prior approaches
and the experimental results demonstrate the efficiency and efficacy of our
proposed approach.
PMID- 26440267
TI - Robust estimation of unbalanced mixture models on samples with outliers.
AB - Mixture models are often used to compactly represent samples from heterogeneous
sources. However, in real world, the samples generally contain an unknown
fraction of outliers and the sources generate different or unbalanced numbers of
observations. Such unbalanced and contaminated samples may, for instance, be
obtained by high density data sensors such as imaging devices. Estimation of
unbalanced mixture models from samples with outliers requires robust estimation
methods. In this paper, we propose a novel robust mixture estimator incorporating
trimming of the outliers based on component-wise confidence level ordering of
observations. The proposed method is validated and compared to the state-of-the
art FAST-TLE method on two data sets, one consisting of synthetic samples with a
varying fraction of outliers and a varying balance between mixture weights, while
the other data set contained structural magnetic resonance images of the brain
with tumors of varying volumes. The results on both data sets clearly indicate
that the proposed method is capable to robustly estimate unbalanced mixtures over
a broad range of outlier fractions. As such, it is applicable to real-world
samples, in which the outlier fraction cannot be estimated in advance.
PMID- 26440268
TI - Semi-automatic segmentation of prostate in CT images via coupled feature
representation and spatial-constrained transductive lasso.
AB - Conventional learning-based methods for segmenting prostate in CT images ignore
the relations among the low-level features by assuming all these features are
independent. Also, their feature selection steps usually neglect the image
appearance changes in different local regions of CT images. To this end, we
present a novel semi-automatic learning-based prostate segmentation method in
this article. For segmenting the prostate in a certain treatment image, the
radiation oncologist will be first asked to take a few seconds to manually
specify the first and last slices of the prostate. Then, prostate is segmented
with the following two steps: (i) Estimation of 3D prostate-likelihood map to
predict the likelihood of each voxel being prostate by employing the coupled
feature representation, and the proposed Spatial-COnstrained Transductive LassO
(SCOTO); (ii) Multi-atlases based label fusion to generate the final segmentation
result by using the prostate shape information obtained from both planning and
previous treatment images. The major contribution of the proposed method mainly
includes: (i) incorporating radiation oncologist's manual specification to aid
segmentation, (ii) adopting coupled features to relax previous assumption of
feature independency for voxel representation, and (iii) developing SCOTO for
joint feature selection across different local regions. The experimental result
shows that the proposed method outperforms the state-of-the-art methods in a real
world prostate CT dataset, consisting of 24 patients with totally 330 images, all
of which were manually delineated by the radiation oncologist for performance
evaluation. Moreover, our method is also clinically feasible, since the
segmentation performance can be improved by just requiring the radiation
oncologist to spend only a few seconds for manual specification of ending slices
in the current treatment CT image.
PMID- 26440269
TI - Spherical hashing: binary code embedding with hyperspheres.
AB - Many binary code embedding schemes have been actively studied recently, since
they can provide efficient similarity search, and compact data representations
suitable for handling large scale image databases. Existing binary code embedding
techniques encode high-dimensional data by using hyperplane-based hashing
functions. In this paper we propose a novel hypersphere-based hashing function,
spherical hashing, to map more spatially coherent data points into a binary code
compared to hyperplane-based hashing functions. We also propose a new binary code
distance function, spherical Hamming distance, tailored for our hypersphere-based
binary coding scheme, and design an efficient iterative optimization process to
achieve both balanced partitioning for each hash function and independence
between hashing functions. Furthermore, we generalize spherical hashing to
support various similarity measures defined by kernel functions. Our extensive
experiments show that our spherical hashing technique significantly outperforms
state-of-the-art techniques based on hyperplanes across various benchmarks with
sizes ranging from one to 75 million of GIST, BoW and VLAD descriptors. The
performance gains are consistent and large, up to 100 percent improvements over
the second best method among tested methods. These results confirm the unique
merits of using hyperspheres to encode proximity regions in high-dimensional
spaces. Finally, our method is intuitive and easy to implement.
PMID- 26440270
TI - Supervised hashing using graph cuts and boosted decision trees.
AB - To build large-scale query-by-example image retrieval systems, embedding image
features into a binary Hamming space provides great benefits. Supervised hashing
aims to map the original features to compact binary codes that are able to
preserve label based similarity in the binary Hamming space. Most existing
approaches apply a single form of hash function, and an optimization process
which is typically deeply coupled to this specific form. This tight coupling
restricts the flexibility of those methods, and can result in complex
optimization problems that are difficult to solve. In this work we proffer a
flexible yet simple framework that is able to accommodate different types of loss
functions and hash functions. The proposed framework allows a number of existing
approaches to hashing to be placed in context, and simplifies the development of
new problem-specific hashing methods. Our framework decomposes the hashing
learning problem into two steps: binary code (hash bit) learning and hash
function learning. The first step can typically be formulated as binary quadratic
problems, and the second step can be accomplished by training a standard binary
classifier. For solving large-scale binary code inference, we show how it is
possible to ensure that the binary quadratic problems are submodular such that
efficient graph cut methods may be used. To achieve efficiency as well as
efficacy on large-scale high-dimensional data, we propose to use boosted decision
trees as the hash functions, which are nonlinear, highly descriptive, and are
very fast to train and evaluate. Experiments demonstrate that the proposed method
significantly outperforms most state-of-the-art methods, especially on high
dimensional data.
PMID- 26440271
TI - Transductive multi-view zero-shot learning.
AB - Most existing zero-shot learning approaches exploit transfer learning via an
intermediate semantic representation shared between an annotated auxiliary
dataset and a target dataset with different classes and no annotation. A
projection from a low-level feature space to the semantic representation space is
learned from the auxiliary dataset and applied without adaptation to the target
dataset. In this paper we identify two inherent limitations with these
approaches. First, due to having disjoint and potentially unrelated classes, the
projection functions learned from the auxiliary dataset/domain are biased when
applied directly to the target dataset/domain. We call this problem the
projection domain shift problem and propose a novel framework, transductive multi
view embedding, to solve it. The second limitation is the prototype sparsity
problem which refers to the fact that for each target class, only a single
prototype is available for zero-shot learning given a semantic representation. To
overcome this problem, a novel heterogeneous multi-view hypergraph label
propagation method is formulated for zero-shot learning in the transductive
embedding space. It effectively exploits the complementary information offered by
different semantic representations and takes advantage of the manifold structures
of multiple representation spaces in a coherent manner. We demonstrate through
extensive experiments that the proposed approach (1) rectifies the projection
shift between the auxiliary and target domains, (2) exploits the complementarity
of multiple semantic representations, (3) significantly outperforms existing
methods for both zero-shot and N-shot recognition on three image and video
benchmark datasets, and (4) enables novel cross-view annotation tasks.
PMID- 26440272
TI - Visual place recognition with repetitive structures.
AB - Repeated structures such as building facades, fences or road markings often
represent a significant challenge for place recognition. Repeated structures are
notoriously hard for establishing correspondences using multi-view geometry. They
violate the feature independence assumed in the bag-of-visual-words
representation which often leads to over-counting evidence and significant
degradation of retrieval performance. In this work we show that repeated
structures are not a nuisance but, when appropriately represented, they form an
important distinguishing feature for many places. We describe a representation of
repeated structures suitable for scalable retrieval and geometric verification.
The retrieval is based on robust detection of repeated image structures and a
suitable modification of weights in the bag-of-visual-word model. We also
demonstrate that the explicit detection of repeated patterns is beneficial for
robust visual word matching for geometric verification. Place recognition results
are shown on datasets of street-level imagery from Pittsburgh and San Francisco
demonstrating significant gains in recognition performance compared to the
standard bag-of-visual-words baseline as well as the more recently proposed
burstiness weighting and Fisher vector encoding.
PMID- 26440273
TI - Acidic phospholipids govern the enhanced activation of IgG-B cell receptor.
AB - B cells that express the isotype-switched IgG-B cell receptor (IgG-BCR) are one
of the driving forces for antibody memory. To allow for a rapid memory IgG
antibody response, IgG-BCR evolved into a highly effective signalling machine.
Here, we report that the positively charged cytoplasmic domain of mIgG (mIgG
tail) specifically interacts with negatively charged acidic phospholipids. The
key immunoglobulin tail tyrosine (ITT) in mIgG-tail is thus sequestered in the
membrane hydrophobic core in quiescent B cells. Pre-disruption of such
interaction leads to excessive recruitment of BCRs and inflated BCR signalling
upon antigen stimulation, resulting in hyperproliferation of primary B cells.
Physiologically, membrane-sequestered mIgG-tail can be released by antigen
engagement or Ca(2+) mobilization in the initiation of B cell activation. Our
studies suggest a novel regulatory mechanism for how dynamic association of mIgG
tail with acidic phospholipids governs the enhanced activation of IgG-BCR.
PMID- 26440274
TI - [Glomerulonephritides].
AB - Many forms of glomerulonephritis, even the more common types belong to the so
called rare diseases; however, they are very important, for example with respect
to health economics as they often affect young people. An example is
immunoglobulin A (IgA) nephropathy, which is the most common cause of end stage
renal disease in young adults. This review summarizes the current knowledge on
the pathogenesis, clinical presentation and therapy of the most common European
types of glomerulonephritis with a special focus on the most recently acquired
knowledge on IgA nephropathy, membranous glomerulonephritis, minimal change
nephropathy and focal segmental glomerulosclerosis (FSGS).
PMID- 26440275
TI - Correction: Observational study assessing demographic, economic and clinical
factors associated with access and utilization of health care services of
patients with multiple sclerosis under treatment with interferon beta-1b
(EXTAVIA).
PMID- 26440277
TI - Maintenance Therapy Improves Survival Outcomes in Patients with Advanced Non
small Cell Lung Cancer.
PMID- 26440276
TI - Brain Function and Upper Limb Outcome in Stroke: A Cross-Sectional fMRI Study.
AB - OBJECTIVE: The nature of changes in brain activation related to good recovery of
arm function after stroke is still unclear. While the notion that this is a
reflection of neuronal plasticity has gained much support, confounding by
compensatory strategies cannot be ruled out. We address this issue by comparing
brain activity in recovered patients 6 months after stroke with healthy controls.
METHODS: We included 20 patients with upper limb paresis due to ischemic stroke
and 15 controls. We measured brain activation during a finger flexion-extension
task with functional MRI, and the relationship between brain activation and hand
function. Patients exhibited various levels of recovery, but all were able to
perform the task. RESULTS: Comparison between patients and controls with voxel
wise whole-brain analysis failed to reveal significant differences in brain
activation. Equally, a region of interest analysis constrained to the motor
network to optimize statistical power, failed to yield any differences. Finally,
no significant relationship between brain activation and hand function was found
in patients. Patients and controls performed scanner task equally well.
CONCLUSION: Brain activation and behavioral performance during finger flexion
extensions in (moderately) well recovered patients seems normal. The absence of
significant differences in brain activity even in patients with a residual
impairment may suggest that infarcts do not necessarily induce reorganization of
motor function. While brain activity could be abnormal with higher task demands,
this may also introduce performance confounds. It is thus still uncertain to what
extent capacity for true neuronal repair after stroke exists.
PMID- 26440278
TI - Regulation of Connective Tissue Growth Factor and Cardiac Fibrosis by an
SRF/MicroRNA-133a Axis.
AB - Myocardial fibrosis contributes to the remodeling of heart and the loss of
cardiac function leading to heart failure. SRF is a transcription factor
implicated in the regulation of a large variety of genes involved in cardiac
structure and function. To investigate the impact of an SRF overexpression in
heart, we developed a new cardiac-specific and tamoxifen-inducible SRF
overexpression mouse model by the Cre/loxP strategy. Here, we report that a high
level overexpression of SRF leads to severe modifications of cardiac
cytoarchitecture affecting the balance between cardiomyocytes and cardiac
fibroblasts and also a profound alteration of cardiac gene expression program.
The drastic development of fibrosis was characterized by intense sirius red
staining and associated with an increased expression of genes encoding
extracellular matrix proteins such as fibronectin, procollagen type 1alpha1 and
type 3alpha1 and especially connective tissue growth factor (CTGF). Furthermore
miR-133a, one of the most predominant cardiac miRNAs, is strongly downregulated
when SRF is overexpressed. By comparison a low level overexpression of SRF has
minor impact on these different processes. Investigation with miR-133a, antimiR
133a and AdSRF-VP16 experiments in H9c2 cardiac cells demonstrated that: 1)-miR
133a acts as a repressor of SRF and CTGF expression; 2)-a simultaneous
overexpression of SRF by AdSRF-VP16 and inhibition of miR-133a by a specific
antimiR increase CTGF expression; 3)-miR-133a overexpression can block the
upregulation of CTGF induced by AdSRF-VP16. Taken together, these findings reveal
a key role of the SRF/CTGF/miR-133a axis in the regulation of cardiac fibrosis.
PMID- 26440279
TI - Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia:
A Retrospective Case Control Study.
AB - BACKGROUND: In developing countries, there is no published report on predicting
factors of severe sepsis in severely acute malnourished (SAM) children having
pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to
identify predicting factors for severe sepsis and assess the outcome of fluid
resuscitation of such children. METHODS: In this retrospective case-control study
SAM children aged 0-59 months, admitted to the Intensive Care Unit (ICU) of the
Dhaka Hospital of the International Centre for Diarrhoeal Disease Research,
Bangladesh from April 2011 through July 2012 with history of cough or difficult
breathing and radiologic pneumonia, who were assessed for severe sepsis at
admission constituted the study population. We compared the pneumonic SAM
children with severe sepsis (cases = 50) with those without severe sepsis
(controls = 354). Severe sepsis was defined with objective clinical criteria and
managed with fluid resuscitation, in addition to antibiotic and other supportive
therapy, following the standard hospital guideline, which is very similar to the
WHO guideline. RESULTS: The case-fatality-rate was significantly higher among the
cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis
after adjusting for potential confounders, lack of BCG vaccination, drowsiness,
abdominal distension, acute kidney injury, and metabolic acidosis at admission
remained as independent predicting factors for severe sepsis in pneumonic SAM
children (p<0.05 for all comparisons). CONCLUSION AND SIGNIFICANCE: We noted a
much higher case fatality among under-five SAM children with pneumonia and severe
sepsis who required fluid resuscitation in addition to standard antibiotic and
other supportive therapy compared to those without severe sepsis. Independent
risk factors and outcome of the management of severe sepsis in our study children
highlight the importance for defining optimal fluid resuscitation therapy aiming
at reducing the case fatality in such children.
PMID- 26440280
TI - Wistar audiogenic rats display abnormal behavioral traits associated with
artificial selection for seizure susceptibility.
AB - Accumulating evidence from different animal models has contributed to the
understanding of the bidirectional comorbidity associations between the epileptic
condition and behavioral abnormalities. A strain of animals inbred to enhance
seizure predisposition to high-intensity sound stimulation, the Wistar audiogenic
rat (WAR), underwent several behavioral tests: forced swim test (FST), open-field
test (OFT), sucrose preference test (SPT), elevated plus maze (EPM), social
preference (SP), marble burying test (MBT), inhibitory avoidance (IAT), and two
way active avoidance (TWAA). The choice of tests aimed to investigate the
correlation between underlying circuits believed to be participating in both
WAR's innate susceptibility to sound-triggered seizures and the neurobiological
substrates associated with test performance. Comparing WAR with its Wistar
counterpart (i.e., resistant to audiogenic seizures) showed that WARs present
behavioral despair traits (e.g., increased FST immobility) but no evidence of
anhedonic behavior (e.g., increased sucrose consumption in SPT) or social
impairment (e.g., no difference regarding juvenile exploration in SP). In
addition, tests suggested that WARs are unable to properly evaluate degrees of
aversiveness (e.g., performance on OFT, EPM, MBT, IAT, and TWAA). The
particularities of the WAR model opens new venues to further untangle the
neurobiology underlying the co-morbidity of behavioral disorders and epilepsy.
This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies,
Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
PMID- 26440281
TI - A Novel Method of Automatic Plant Species Identification Using Sparse
Representation of Leaf Tooth Features.
AB - Automatic species identification has many advantages over traditional species
identification. Currently, most plant automatic identification methods focus on
the features of leaf shape, venation and texture, which are promising for the
identification of some plant species. However, leaf tooth, a feature commonly
used in traditional species identification, is ignored. In this paper, a novel
automatic species identification method using sparse representation of leaf tooth
features is proposed. In this method, image corners are detected first, and the
abnormal image corner is removed by the PauTa criteria. Next, the top and bottom
leaf tooth edges are discriminated to effectively correspond to the extracted
image corners; then, four leaf tooth features (Leaf-num, Leaf-rate, Leaf
sharpness and Leaf-obliqueness) are extracted and concatenated into a feature
vector. Finally, a sparse representation-based classifier is used to identify a
plant species sample. Tests on a real-world leaf image dataset show that our
proposed method is feasible for species identification.
PMID- 26440282
TI - AMPK Protects Leukemia-Initiating Cells in Myeloid Leukemias from Metabolic
Stress in the Bone Marrow.
AB - How cancer cells adapt to metabolically adverse conditions in patients and strive
to proliferate is a fundamental question in cancer biology. Here we show that AMP
activated protein kinase (AMPK), a metabolic checkpoint kinase, confers metabolic
stress resistance to leukemia-initiating cells (LICs) and promotes
leukemogenesis. Upon dietary restriction, MLL-AF9-induced murine acute myeloid
leukemia (AML) activated AMPK and maintained leukemogenic potential. AMPK
deletion significantly delayed leukemogenesis and depleted LICs by reducing the
expression of glucose transporter 1 (Glut1), compromising glucose flux, and
increasing oxidative stress and DNA damage. LICs were particularly dependent on
AMPK to suppress oxidative stress in the hypoglycemic bone marrow environment.
Strikingly, AMPK inhibition synergized with physiological metabolic stress caused
by dietary restriction and profoundly suppressed leukemogenesis. Our results
indicate that AMPK protects LICs from metabolic stress and that combining AMPK
inhibition with physiological metabolic stress potently suppresses AML by
inducing oxidative stress and DNA damage.
PMID- 26440283
TI - Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and
Antitubercular Compounds.
AB - Tuberculosis (TB) remains a worldwide problem and the need for new drugs is
increasingly more urgent with the emergence of multidrug- and extensively-drug
resistant TB. Inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) from
Mycobacterium tuberculosis (Mtb) is an attractive drug target. The enzyme
catalyzes the conversion of inosine 5'-monophosphate into xanthosine 5'
monophosphate with the concomitant reduction of NAD+ to NADH. This reaction
controls flux into the guanine nucleotide pool. We report seventeen selective
IMPDH inhibitors with antitubercular activity. The crystal structures of a
deletion mutant of MtbIMPDH2 in the apo form and in complex with the product XMP
and substrate NAD+ are determined. We also report the structures of complexes
with IMP and three structurally distinct inhibitors, including two with
antitubercular activity. These structures will greatly facilitate the development
of MtbIMPDH2-targeted antibiotics.
PMID- 26440284
TI - Lipoteichoic acid modulates inflammatory response in macrophages after
phagocytosis of titanium particles through Toll-like receptor 2 cascade and
inflammasomes.
AB - Toll-like receptor 2 (TLR2) and nucleotide-binding and oligomerization domain
like receptors with a pyrin domain 3 (NLRP3) inflammasomes have been presumed to
participate in the pathogenesis of aseptic implant loosening. The aim of this
study is to analyze the cellular localization of TLR2 and NLRP3 inflammasomes in
the periprosthetic tissue from aseptically loose hip implants as well as the
expression of these molecules in macrophages stimulated in vitro with titanium
particles (Ti) coated with lipoteichoic acid (LTA). Using immunohistochemistry,
immunoreactivity of TLR2 and NLRP3 inflammasomes was found in macrophages within
the foreign body granulomatosis. Using RAW264.7 cells, stimulation with Ti
increased the messenger RNA (mRNA) levels of TLR2 and TNF-alpha. Stimulation with
LTA-coated Ti enhanced mRNA levels of NLRP3 and IL-1beta, whereas reinforced
secretion of IL-1beta was not detected in spite of marked release of TNF-alpha.
Finally, the same cells with silenced Irak2, an adaptor protein in the TLR2
cascade, suppressed this NLRP3 upregulation. This study suggests that TLR2 and
NLRP3 inflammasomes are factors involved in cross-talk mediating the foreign body
type response to wear particles. In addition, discrepant behavior in the release
between TNF-alpha and IL-1beta release may explain the variable pathomechanisms
of aseptic implant loosening without acute inflammatory reactions.
PMID- 26440285
TI - Rapid chiral separation of racemic cetirizine in human plasma using subcritical
fluid chromatography-tandem mass spectrometry.
AB - A method for fast chiral separation of cetirizine and quantitation of
levocetirizine in human plasma using subcritical fluid chromatography with tandem
mass spectrometry was developed and validated. The chromatographic separation was
performed using a Chiralpak IE column (2.1 mm*150 mm, 5 MUm) with an isocratic
elution of CO2/organic modifier (55/45, v/v) at a flow rate of 0.85 mL/min. The
organic modifier was composed of water/methanol (5/95, v/v). The makeup flow was
optimized at water/methanol (10/90, v/v) and 0.2 mL/min. The most influential
parameters on the separation of cetirizine affecting resolution, retention time
and sensitivity were selected by fractional factorial design. The 3 selected
factors were optimized by response surface methodology. Tandem mass spectrometry
was used at electrospray ionization, positive ion mode, and multiple-reaction
monitoring mode. Isotope-labeled cetirizine-d4 was used as the internal standard.
The sample preparation of human plasma was conducted by solid phase extraction of
hydrophilic-lipophilic balance (HLB) type. The developed method was validated for
selectivity, linearity, precision, accuracy, recovery, limit of quantitation
(LOQ), and limit of detection (LOD). The real human plasma samples were analyzed
and the pharmacokinetic results were compared with results of previous research.
The developed method was found to be reliable based on the similarity between the
results of the current and previous methods. The chiral separation for cetirizine
and economic feasibility were compared with those of previous studies using
normal phase-HPLC or reversed phase-HPLC. The established analytical method could
be successfully applied to pharmacokinetic study with reduction in the analysis
time and costs.
PMID- 26440286
TI - A novel LC-MS/MS assay for the simultaneous determination of melatonin and its
two major metabolites, 6-hydroxymelatonin and 6-sulfatoxymelatonin in dog plasma:
Application to a pharmacokinetic study.
AB - A convenient and specific liquid chromatography-tandem mass spectrometry method
was developed and validated for the simultaneous quantification of melatonin
(MEL) and its major metabolites, 6-hydroxymelatonin (6-O-MEL) and 6
sulfatoxymelationin (S-O-MEL) in dog plasma. After plasma samples were
deproteinized with acetonitrile, the post-treatment samples were analyzed on a
Phenomenex Kinetex C18 column (50*2.1 mm, 1.7 MUm) interfaced with a triple
quadrupole tandem mass spectrometer. Electrospray ionization mode (ESI) and
multiple reaction monitoring were used to assay MEL and its metabolites.
Acetonitrile and 5 mM ammonium acetate were used as the mobile phase with a
gradient elution at a flow rate of 0.2 mL/min. The analytical run time of 6.5 min
was divided into two periods according to ionization mode. S-O-MEL was monitored
in negative ionization mode (period 1), while MEL and 6-O-MEL were detected in
positive ionization mode (period 2). All calibration curves showed good linearity
(r>0.991) over the concentration range with a lower limit of quantification
(LLOQ) of 0.02 ng/mL for MEL, 0.04 ng/mL for 6-O-MEL and 0.50 ng/mL for S-O-MEL.
The intra- and inter-day precision was within 13.5% in terms of relative standard
deviation (RSD%) and the accuracy within 13.0% in terms of relative error. This
convenient and specific LC-MS/MS method was successfully applied to the
pharmacokinetic study of MEL and its metabolites in Beagle dogs after an oral
dose of 2.0mg MEL. After ingestion of MEL, S-O-MEL was the predominant component
circulating in blood. 6-O-MEL showed similar pharmacokinetic profile to that of
MEL.
PMID- 26440287
TI - Chiral separation of asenapine enantiomers by capillary electrophoresis and
characterization of cyclodextrin complexes by NMR spectroscopy, mass spectrometry
and molecular modeling.
AB - The enantiomers of asenapine maleate (ASN), a novel antipsychotic against
schizophrenia and mania with bipolar I disorder have been separated by
cyclodextrin (CD) modified capillary zone electrophoresis for the first time. 15
different CDs were screened as complexing agents and chiral selectors,
investigating the stability of the inclusion complexes and their
enantiodiscriminating capacities. Although initially, none of the applied chiral
selectors gave baseline separation, beta-CD proved to be the most effective
chiral selector. In order to improve resolution, an orthogonal experimental
design was employed, altering the concentration of background electrolyte,
organic modifier, pH, capillary temperature and applied voltage in a multivariate
manner. The developed method (160 mM TRIS-acetate buffer pH 3.5, 7 mM beta-CD, at
20 degrees C, applying 15 kV) was successful for baseline separation of ASN
enantiomers (R(s)=2.40+/-0.04). Our method was validated according to ICH
guidelines and proved to be sensitive, linear, accurate and precise for the
chiral separation of ASN. Properties of the inclusion complexes, such as
stoichiometry, atomic level intermolecular host-guest connections are proposed on
the basis of ROESY NMR measurement, ESI-MS spectrometry and molecular modeling
studies. It was found that the ASN-beta-CD complex is of 1:1 composition, and
either of the aromatic rings can be accommodated in the beta-CD cavity.
PMID- 26440289
TI - Police Officers' Attitudes and Challenges With Charging Stalking.
AB - This study examined 2 groups of police officers on perceived barriers and
attitudes related to charging stalking. Police officers who categorized into
groups based on if they had (n=73) or had not (n=90) previously charged stalking.
Results indicated that officers who had never charged stalking viewed stalking as
less dangerous, believed that officers do not file reports when called for
stalking, and perceived all barriers related to charging stalking as more
challenging than officers who had previously charged stalking. Officers who
charged stalking had greater comprehension of the stalking statute and identified
specific problems within the statute. The results have implications related to
improving specialized police training in an effort to better protect victims of
stalking and increase stalking charges.
PMID- 26440288
TI - Preclinical pharmacokinetic evaluation of praziquantel loaded in poly (methyl
methacrylate) nanoparticle using a HPLC-MS/MS.
AB - Praziquantel (PZQ) is the drug recommended by the World Health Organization for
treatment of schistosomiasis. However, the treatment of children with PZQ tablets
is complicated due to difficulties to adapt the dose and the extremely bitter
taste of PZQ. For this reason, poly (methyl methacrylate) nanoparticles loaded
with Praziquantel (PZQ-NP) were developed for preparation of a new formulation to
be used in the suspension form. For this reason, the main aim of the present
study was to evaluate the pharmacokinetic (PK) profile of PZQ-NP, through HPLC
MS/MS assays. Analyses were performed with an Omnisphere C18 column (5.0 MUm*4.6
mm*150.0 mm), using a mixture of an aqueous solution containing 0.1 wt% of formic
acid and methanol (15:85-v/v) as the mobile phase at a flow rate of 0.800mL/min.
Detection was performed with a hybrid linear ion-trap triple quadrupole mass
spectrometer with multiple reactions monitoring in positive ion mode via
electrospray ionization. The monitored transitions were m/z 313.18>203.10 for PZQ
and m/z 285.31>193.00 for the Internal Standard. The method was validated with
the quantification limit of 1.00 ng/mL, requiring samples of 25 MUL for analyses.
Analytic responses were calibrated with known concentration data, leading to
correlation coefficients (r) higher than 0.99. Validation performed with rat
plasma showed that PZQ was stable for at least 10 months when stored below -70
degrees C (long-term stability), for at least 17 h when stored at room
temperature (RT, 22 degrees C) (short-term stability), for at least 47 h when
stored at room temperature in auto-sampler vials (post-preparative stability) and
for at least 8 successive freeze/thaw cycles at -70 degrees C. For PK assays,
Wistar rats, weighing between 200 and 300 g were used. Blood samples were
collected from 0 to 24 h after oral administration of single doses of 60 mg/kg of
PZQ-NP or raw PZQ (for the control group). PZQ was extracted from plasma by
liquid-liquid extraction with terc-butyl methyl ether. The values obtained for
maximum concentration (C(max)) and area under curve (AUC) for the PZQ-NP group
were about 3 times smaller than the respective values obtained for the control
group. However, the time for achieving maximum concentration (T(max)), the
elimination constant (Ke) and the half-life time of elimination (T(1/2beta)) were
not statistically different. These results suggest that PZQ absorption is
probably the rate-limiting step for obtainment of better PK parameters for PZQ
NP. Thus, further studies are needed to understand both the PZQ-NP absorption
mechanisms and the drug diffusion process through the polymer matrix in vivo, in
order to improve the PZQ-NP release profile.
PMID- 26440290
TI - Synchrotron radiation based X-ray fluorescence shows changes in the elemental
composition of the human substantia nigra in aged brains.
AB - Human brain aging is considered to be the leading risk factor for a variety of
neurodegenerative alterations. In particular, it is thought that the human
substantia nigra might play a pivotal role in age-associated dopamine depletion
which could be responsible for neuronal demise and subsequent emergence of
different neurological alterations. A plethora of neurochemical redox- and non
redox-driven mechanisms is mainly associated with modifications in the elemental
composition of both neuromelanin-pigmented neurons and extraneuronal spaces in
the human substantia nigra pars compacta (SNpc). An age-associated variation in
the content of Fe, Cu, Zn and Ca has recently received great interest in
neurology, as these elements are implicated in different biochemical mechanisms
underlying malicious neurodegenerative disorders, including Parkinson's and
Alzheimer's diseases. Interestingly, to the best our knowledge, there is lack of
a comprehensive study on age-associated variation in the elemental composition of
the human SNpc. In that respect, the aim of the present study was to make a
preliminary attempt to unravel some of the age-associated mechanisms responsible
for the metabolism of some redox-active and redox-inactive elements in the
elderly. To do so, substantia nigra tissue specimens, drawn from 37 individuals
who deceased without any signs of neurodegeneration, were subjected to
spectroscopic studies using synchrotron radiation based X-ray fluorescence. Both
neuromelanin-pigmented neurons and extraneuronal areas were studied. It appears
that in the neurons, Fe tends to decrease, whilst Cu, Zn and Ca were found to
accumulate as an individual gets older.
PMID- 26440291
TI - Smartphone Assisted Slit Lamp Free Anterior Segment Imaging: A novel technique in
teleophthalmology.
PMID- 26440292
TI - Is the Post-Radical Prostatectomy Gleason Score a Valid Predictor of Mortality
after Neoadjuvant Hormonal Treatment?
AB - PURPOSE: To evaluate the validity of the Gleason score after neoadjuvant hormonal
treatment as predictor of disease-specific mortality after radical prostatectomy.
PATIENTS AND METHODS: A total of 2,880 patients with a complete data set and a
mean follow-up of 10.3 years were studied; 425 of them (15%) had a history of
hormonal treatment prior to surgery. The cumulative incidence of deaths from
prostate cancer was determined by univariate and multivariate competing risk
analysis. Cox proportional hazard models for competing risks were used to study
combined effects of the variables on prostate cancer-specific mortality. RESULTS:
A higher portion of specimens with a history of neoadjuvant hormonal treatment
were assigned Gleason scores of 8-10 (28 vs. 17%, p < 0.0001). The mortality
curves in the Gleason score strata <8 vs. 8-10 were at large congruent in
patients with and without neoadjuvant hormonal treatment. In patients with
neoadjuvant hormonal treatment, a Gleason score of 8-10 was an independent
predictor of prostate cancer-specific mortality; the hazard ratio was, however,
somewhat lower than in patients without neoadjuvant hormonal treatment.
CONCLUSION: This study suggests that the prognostic value of the post-radical
prostatectomy Gleason score is not meaningfully jeopardized by heterogeneous
neoadjuvant hormonal treatment in a routine clinical setting.
PMID- 26440293
TI - Making health care safer: What is the contribution of health psychology?
AB - While health care brings great benefits, all treatments, and many investigations,
carry some risk. As patients, we should be told of the risks of specific
treatments but we are also at risk from failings in the health care system
itself. We suggest that, while there are many examples of individual health
psychologists who have made important contributions, this has not yet translated
into a broader disciplinary engagement. Health psychologists have devoted much
more attention to patients and devoted much less attention to the potentially
huge impact of studying and intervening with staff, clinical practice, and
organizations. We believe that there are considerable opportunities for health
psychology to engage more closely with patient safety and, more importantly, that
this would be of great benefit to both patients and staff. Statement of
contribution What is already known on this subject? While health care brings
great benefits, all treatments, and many investigations, carry some risk.
Patients are also at risk from failings in the health care system itself. Studies
using review of medical records in many countries have found that between 8% and
12% of patients in hospital suffer an unintended harm due to health care. What
does this study add? There are many examples of individual psychologists who have
made important contributions, but this has not yet translated into a broader
disciplinary engagement. There are considerable opportunities for health
psychology to engage more closely with patient safety. These include health
behaviour change, teamwork, communication after medical error, diagnosis and
decision making, organisational culture, and improving compliance with rules and
standards. Psychologists providing a clinical service to specialist services in
any area could expand their remit from supporting patients to a more general
support and engagement with safety and quality initiatives. Health psychologists
have models to understand the behaviour of people, and recent developments in
changing behaviour should be applicable to health professionals in addition to
their patients.
PMID- 26440294
TI - Preoperative surgical simulation of laparoscopic adrenalectomy for neuroblastoma
using a three-dimensional printed model based on preoperative CT images.
AB - BACKGROUND: Three-dimensional (3D) printed models based on computed tomography
(CT) images facilitate the visualization of complex structures and are useful for
understanding the surgical anatomy preoperatively. We developed a preoperative
surgical simulation method using a 3D printed model based on CT images obtained
prior to laparoscopic adrenalectomy for adrenal neuroblastomas (NBs). MATERIALS
AND METHODS: The multi-detector CT images were transferred to a 3D workstation,
and 3D volume data were obtained by reconstructing the sections. A model was made
with a 3D printer using acrylic ultraviolet curable resin. The adrenal tumor,
kidney, renal vein and artery, inferior vena cava, aorta, and outer body were
fabricated. The pneumoperitoneum, insertion of trocars, and laparoscopic view
were all attainable in this model. We used this model for three cases with
adrenal NB. RESULTS: We used this model to discuss the port layout before the
operation and to simulate the laparoscopic view and range of forceps movement.
All three cases with NB were completely resected without any surgical
complications. CONCLUSIONS: The surgical simulation using 3D printed models based
on preoperative CT images for adrenal NB was very useful for understanding the
patient's surgical anatomy and for planning the surgical procedures, especially
for determining the optimal port layout.
PMID- 26440295
TI - A combined cumulative threshold spectra and digital reconstruction analysis
reveal structural alterations of microglia within the prefrontal cortex following
low-dose LPS administration.
AB - Sickness behaviors have become the focus of great interest in recent years as
they represent a clear case of how peripheral disturbances in immune signaling
can disrupt quite complex behaviors. In the current study, we were interested in
examining whether we could identify any significant morphological disturbances in
microglia associated with these sickness-like behaviors in adult male Sprague
Dawley rats. We chose lipopolysaccharide (LPS 100 MUg/kg/i.p.), to induce
sickness-like behaviors as it is the most well-validated approach to do so in
rodents and humans. We were particularly interested in examining changes in
microglia within the prefrontal cortex (PFC) as several recent neuroimaging
studies have highlighted significant functional changes in this region following
peripheral LPS administration. Paraformaldehyde-fixed tissue was collected from
animals 24h post LPS administration and labeled immunohistochemically with an
antibody directed to bind to Iba-1, a protein known to be involved in the
structural remodeling of microglia. To analyze changes, we have made use of two
recently described image analysis procedures. The first is known as cumulative
threshold spectra (CTS) analysis. The second involves the unsupervised digital
reconstruction of microglia. We undertook these complementary analysis of
microglial cells in the both the pre- and infralimbic divisions of the PFC. Our
results indicated that microglial soma size was significantly enlarged, while
cell processes had contracted slightly following LPS administration. To our
knowledge this study is to first to definitely demonstrate substantial microglial
disturbances within the PFC following LPS delivered at a dose that was sufficient
to induce significant sickness-like behavior.
PMID- 26440296
TI - Stereotaxic Magnetic Resonance Imaging Brain Atlases for Infants from 3 to 12
Months.
AB - BACKGROUND: Accurate labeling of brain structures within an individual or group
is a key issue in neuroimaging. Methods for labeling infant brains have depended
on the labels done on adult brains or average magnetic resonance imaging (MRI)
templates based on adult brains. However, the features of adult brains differ in
several ways from infant brains, so the creation of a labeled stereotaxic atlas
based on infants would be helpful. The current work builds on the recent creation
of age-appropriate average MRI templates during the first year (3, 4.5, 6, 7.5,
9, and 12 months) by creating anatomical label sets for each template. METHODS:
We created stereotaxic atlases for the age-specific average MRI templates. Manual
delineation of cortical and subcortical areas was done on the average templates
based on infants during the first year. We also applied a procedure for automatic
computation of macroanatomical atlases for individual infant participants using
two manually segmented adult atlases (Hammers, LONI Probabilistic Brain Atlas
LPBA40). To evaluate our methods, we did manual delineation of several cortical
areas on selected individuals from each age. Linear and nonlinear registration of
the individual and average template was used to transform the average atlas into
the individual participant's space, and the average-transformed atlas was
compared to the individual manually delineated brain areas. We also applied these
methods to an external data set - not used in the atlas creation - to test
generalizability of the atlases. RESULTS: Age-appropriate manual atlases were the
best fit to the individual manually delineated regions, with more error seen at
greater age discrepancy. There was a close fit between the manually delineated
and the automatically labeled regions for individual participants and for the age
appropriate template-based atlas transformed into participant space. There was
close correspondence between automatic labeling of individual brain regions and
those from the age-appropriate template. These relationships held even when
tested on an external set of images. CONCLUSION: We have created age-appropriate
labeled templates for use in the study of infant development at 6 ages (3, 4.5,
6, 7.5, 9, and 12 months). Comparison with manual methods was quite good. We
developed three stereotaxic atlases (one manual, two automatic) for each infant
age, which should allow more fine-grained analysis of brain structure for these
populations than was previously possible with existing tools. The template-based
atlases constructed in the current study are available online
(http://jerlab.psych.sc.edu/NeurodevelopmentalMRIDatabase).
PMID- 26440297
TI - The impact of altering filling pressures in diagnostic outpatient hysteroscopy on
the procedure completion rates and associated pain: a randomised double-blind
controlled trial.
AB - BACKGROUND: Several studies have compared different distension media and
analgesics to optimise the efficiency of outpatient hysteroscopy. However,
studies comparing different uterine filling pressures are scarce. AIM: The
objective of this study was to evaluate and compare different uterine filling
pressures during diagnostic outpatient hysteroscopy in an attempt to find the
optimal pressure allowing adequate visualisation while minimising pain and
increasing patient satisfaction. MATERIALS AND METHODS: This was a double-blind
randomised controlled trial. A total of 240 women who had diagnostic outpatient
hysteroscopy were randomly divided into three equal groups: the uterine filling
pressure was 30 mm Hg in group 1, 50 mm Hg in group 2 and 80 mm Hg in group 3.
The primary outcome was adequate visualisation, and secondary outcomes were the
proportion of completed procedures, pain perceived during the procedure,
immediately after the procedure and 30 min later. RESULTS: Adequate visualisation
was lower in group 1 (88.7% vs 97.5% and 98.7%; P = 0.009), but was not different
between groups 2 and 3 (P > 0.999). The proportion of completed procedures was
not different among the groups. There was a progressive increase in pain scores
from the lower to the higher pressure groups during the procedure, immediately
after the procedure and 30 min after completing the procedure. CONCLUSION:
Uterine filling pressure of 50 mm Hg was associated with better visualisation
than 30 mm Hg and lower pain scores than that of 80 mmHg with no difference in
the proportion of completed procedures.
PMID- 26440298
TI - The Bacterial and Fungal Diversity of an Aged PAH- and Heavy Metal-Contaminated
Soil is Affected by Plant Cover and Edaphic Parameters.
AB - Industrial wasteland soils with aged PAH and heavy metal contaminations are
environments where pollutant toxicity has been maintained for decades. Although
the communities may be well adapted to the presence of stressors, knowledge about
microbial diversity in such soils is scarce. Soil microbial community dynamics
can be driven by the presence of plants, but the impact of plant development on
selection or diversification of microorganisms in these soils has not been
established yet. To test these hypotheses, aged-contaminated soil samples from a
field trial were collected. Plots planted with alfalfa were compared to bare soil
plots, and bacterial and fungal diversity and abundance were assessed after 2 and
6 years. Using pyrosequencing of 16S rRNA gene and ITS amplicons, we showed that
the bacterial community was dominated by Proteobacteria, Actinobacteria, and
Bacteroidetes and was characterized by low Acidobacteria abundance, while the
fungal community was mainly represented by members of the Ascomycota. The short
term toxic impact of pollutants usually reduces the microbial diversity, yet in
our samples bacterial and fungal species richness and diversity was high
suggesting that the community structure and diversity adapted to the contaminated
soil over decades. The presence of plants induced higher bacterial and fungal
diversity than in bare soil. It also increased the relative abundance of
bacterial members of the Actinomycetales, Rhizobiales, and Xanthomonadales orders
and of most fungal orders. Multivariate analysis showed correlations between
microbial community structure and heavy metal and PAH concentrations over time,
but also with edaphic parameters (C/N, pH, phosphorus, and nitrogen
concentrations).
PMID- 26440300
TI - Cis-Trans Conformational Analysis of delta-Azaproline in Peptides.
AB - The cis-trans isomerization and conformer specificity of delta-azaproline and its
carbamate-protected form in linear and cyclic peptides were investigated using
NMR and alpha-chymotrypsin assay. Comparisons of the chemical shift value of the
alpha-hydrogen in each case of delta-azaproline-containing peptides with
conformer-specific locked diketopiperazines reveal the fact that an upfield
chemical shift value corresponds to cis conformer and a downfield value
corresponds to a trans conformer. delta-Azaproline adopts cis-conformation in
simple amides, dipeptides, and tripeptides whereas its carbamate-protected form
adopts trans-conformation. In the case of longer, linear or cyclic peptides, vice
versa results are obtained. Interestingly, in all these peptides exclusively one
conformer, either cis or trans, is stabilized. This cis-trans isomerization is
independent of both temperature and solvents; only the delta-nitrogen protecting
group plays key role in the isomerization. delta-Azaproline is conformer-specific
in either of its protected or deprotected forms, which is a unique property of
this proline. Unlike other covalently modified proline surrogates, this
isomerization of delta-azaproline can be tuned easily by a protecting group. The
mechanism of cis-trans isomerization of delta-azaproline during deprotection and
reprotection is supported by theoretical calculations.
PMID- 26440299
TI - Comparative cytotoxicity and genotoxicity of soluble and particulate hexavalent
chromium in human and hawksbill sea turtle (Eretmochelys imbricata) skin cells.
AB - Chromium is both a global marine pollutant and a known human health hazard. In
this study, we compare the cytotoxicity and genotoxicity of both soluble and
particulate chromate in human and hawksbill sea turtle (Eretmochelys imbricata)
skin fibroblasts. Our data show that both soluble and particulate Cr(VI) induce
concentration-dependent increases in cytotoxicity, genotoxicity, and
intracellular Cr ion concentrations in both human and hawksbill sea turtle
fibroblasts. Based on administered concentration, particulate and soluble Cr(VI)
were more cytotoxic and clastogenic to human cells than sea turtle cells. When
the analysis was based on the intracellular concentration of Cr, the data showed
that the response of both species was similar. The one exception was the
cytotoxicity of intracellular Cr ions from soluble Cr(VI), which caused more
cytotoxicity in sea turtle cells (LC50=271MUM) than that of human cells
(LC50=471MUM), but its clastogenicity was similar between the two species. Thus,
adjusting for differences in uptake indicated that the explanation for the
difference in potency was mostly due to uptake rather than differently affected
mechanisms. Overall these data indicate that sea turtles may be a useful sentinel
for human health responses to marine pollution.
PMID- 26440301
TI - Biological parameters of interbreeding subspecies of Meccus phyllosomus
(Hemiptera: Reduviidae: Triatominae) in western Mexico.
AB - Understanding the biological parameters of some triatomine subspecies of Meccus
phyllosomus (Burmeister) is a crucial first step in estimating the
epidemiological importance of this group. Biological parameters related to egg
eclosion, egg-to-adult development time, number of blood meals to moult,
percentage of females at the end of the cycle, number of laid eggs, and the
accumulative mortality for each instar of three M. phyllosomus subspecies [Meccus
phyllosomus pallidipennis (Stal), Meccus phyllosomus longipennis (Usinger), and
Meccus phyllosomus picturatus (Usinger)] as well as their laboratory hybrids were
evaluated and compared. No significant differences (P > 0.05) were recorded among
the experimental hybrids (M. p. longipennis * M. p. pallidipennis, M. p.
longipennis * M. p. picturatus, M. p. pallidipennis * M. p. picturatus) and
reciprocal cohorts. In five of the six studied parameters (egg eclosion, egg-to
adult development time, number of blood meals to moult, number of laid eggs and
accumulative mortality), with the exception of the non-significant percentage of
females obtained among all the studied cohorts, at least one of the parental
cohorts in each set of crosses exhibited better fitness results than by those of
their hybrid descendants. The lack of hybrid fitness in our study indicates the
maintenance of reproductive isolation of parental genotypes. Moreover, the
results lead us to propose that an incipient speciation process by distance is
currently developing among the three studied subspecies, increasing the
differences between them that modify the transmission efficiency of Trypanosoma
cruzi to human beings in Mexico.
PMID- 26440302
TI - Pharmacokinetic Characteristics and Clinical Outcomes of Vancomycin in Young
Children With Various Degrees of Renal Function.
AB - Although vancomycin pharmacokinetics are affected by age and renal function in
adults and older children, its pharmacokinetics in children aged 1 month to 2
years remained unclear. We investigated clinical outcome and nephrotoxicity in
younger children with renal insufficiency who were treated with vancomycin. One
hundred and ten children aged 1 month to 2 years were enrolled, and they were
divided into 3 groups: normal renal function (group A), mild renal insufficiency
(group B), and moderate renal insufficiency (group C). A population
pharmacokinetic model was established. Significant differences were observed for
trough concentration, AUC0-24 h , CL, and t1/2 in the 3 groups. When given at 40
mg/kg per day, 36.4%, 62.5%, and 85.0% of children achieved the target of AUC/MIC
>= 400, and 47.0%, 70.8%, and 95% of children obtained early good clinical
outcomes in groups A, B, and C (P < .05), respectively. One child in group A and
4 children in group C suffered from acute kidney injury. These results indicated
that children with renal insufficiency readily achieved the target AUC/MIC but
were at increased risk of nephrotoxicity. Vancomycin clearance and creatinine
clearance were not correlated with each other in children with renal
insufficiency, indicating that both renal function and serum concentration should
be monitored during vancomycin therapy.
PMID- 26440303
TI - A Straightforward Route to Potent Phenolic Chain-Breaking Antioxidants by Acid
Promoted Transposition of 1,4-Benzo[b]oxathiines to Dihydrobenzo[b]thiophenes.
AB - The transformation of simple phenols with limited antioxidant activity into
potent chain-breaking antioxidants was achieved by a three-step protocol,
consisting of the conversion of phenols into 1,4-benzo[b]oxathiines followed by
an unprecedented acid-promoted transposition to o
hydroxydihydrobenzo[b]thiophenes, or dihydrobenzo[de]thiochromenes, starting from
phenols or naphthols, respectively. These derivatives, bearing a benzo-fused
heterocycle with a sulfide sulfur ortho to the phenolic OH, have a rate constant
of reaction with alkylperoxyl radicals (kinh ) comparable to that of alpha
tocopherol. A solid rationale for the transposition mechanism as well as for the
structure-antioxidant activity relationship is presented.
PMID- 26440304
TI - Rational Design of Polynuclear Organometallic Assemblies from a Simple
Heteromultifunctional Ligand.
AB - In modern coordination chemistry, supramolecular coordination complexes take
advantage of ligand design to control the shapes and sizes of such architectures.
Here we describe how to utilize starting building blocks and a multifunctional
ligand to rationally design and synthesize different types of discrete
assemblies. Using a hydroxamate ligand featuring two pair of chelating sites
together with half-sandwich iridium and rhodium fragments, we were able to
construct a series multinuclear organometallic macrocycles and cages through
stepwise coordination-driven self-assembly. Experimental observations, supported
by computational work, show that selective coordination modes were ascribed to
the significant electronic density differences of the two chelating sites, (O,O')
and (N,N'). The results underline the advantages of the discrimination between
soft and hard binding sites, and suggest that hydroxamic acids can be used as a
versatile class of facile multifunctional scaffold for the construction of novel
two-dimensional and three-dimensional architectures.
PMID- 26440305
TI - Elevated serum uric acid after injury correlates with the early acute kidney in
severe burns.
AB - OBJECTIVE: Early acute kidney injury (AKI) is one of the most serious and common
complications in the early stage of severe burns, but the pathological mechanisms
still need to be elucidated. High uric acid (UA) has been found to be correlated
with renal dysfunction in some experimental and clinical studies; however, the
study of the dynamic correlation between AKI and UA in severe burns is still
lacking. METHODS: The diagnosis and classification of AKI were performed
according to RIFLE criteria, UA, serum creatinine (Scr), estimated glomerular
filtration rate (eGFR), C-reactive protein (CRP) and lactic acid (LA) were
dynamically monitored within 2 days after injury in 59 severely burned patients.
RESULTS: Within 2 days after injury, AKI occurred in 23 of 59 patients (risk in
12 cases, injury in seven cases and failure in four cases), UA level in AKI
patients was significantly higher than that in No-AKI patients, and referring to
the cutoff level of UA (375.5 MUmol/l) from ROC curve for predicting AKI, the
abnormal increase of UA levels was earlier than acute deterioration of renal
function in most of the AKI patients after injury. Among AKI patients, the
Scr/eGFR levels were closely related to UA levels for 2 days after injury.
Moreover, UA level in cases with severe grade of AKI was significantly higher
than that in those with less severe grade of AKI. Furthermore, there was a
positive correlation between UA and CRP for 2 days after injury in AKI patients,
and a significant correlation between CRP and Scr/eGFR was found 1 day after
injury. The positive correlation was also found between LA and UA after injury in
AKI patients. CONCLUSION: The results suggest that elevated serum UA after injury
due to hypoxia is closely correlated with early AKI after severe burns, and UA
related aberrant inflammation also appears to be one of the pathogenic factors,
providing the useful information for potential therapy.
PMID- 26440306
TI - Long term outcomes data for the Burns Registry of Australia and New Zealand: Is
it feasible?
AB - BACKGROUND: Incorporating routine and standardised collection of long term
outcomes following burn into burn registries would improve the capacity to
quantify burn burden and evaluate care. AIMS: To evaluate methods for collecting
the long term functional and quality of life outcomes of burns patients and
establish the feasibility of implementing these outcomes into a multi-centre
burns registry. METHODS: Five Burns Registry of Australia and New Zealand (BRANZ)
centres participated in this prospective, longitudinal study. Patients admitted
to the centres between November 2009 and November 2010 were followed-up at 1, 6,
12 and 24-months after injury using measures of burn specific health, health
status, fatigue, itch and return to work. Participants in the study were compared
to BRANZ registered patients at the centres over the study timeframe to identify
participation bias, predictors of successful follow-up were established using a
Generalised Estimating Equation model, and the completion rates by mode of
administration were assessed. RESULTS: 463 patients participated in the study,
representing 24% of all BRANZ admissions in the same timeframe. Compared to all
BRANZ patients in the same timeframe, the median %TBSA and hospital length of
stay was greater in the study participants. The follow-up rates were 63% at 1
month, 47% at 6-months; 40% at 12-months, and 21% at 24-months after injury, and
there was marked variation in follow-up rates between the centres. Increasing
age, greater %TBSA and opt-in centres were associated with greater follow-up.
Centres which predominantly used one mode of administration experienced better
follow-up rates. CONCLUSIONS: The low participation rates, high loss to follow-up
and responder bias observed indicate that greater consideration needs to be given
to alternative models for follow-up, including tailoring the follow-up protocol
to burn severity or type.
PMID- 26440307
TI - Warming alters the body shape of European perch Perca fluviatilis.
AB - The consequences of elevated temperature on body shape were investigated by
comparing European perch Perca fluviatilis from the Forsmark area of the Baltic
Sea to P. fluviatilis from a nearby Biotest enclosure. The Biotest is a man-made
enclosure within the Baltic Sea that has received warm water from a nuclear power
plant since 1980, resulting in temperatures that are elevated 5-10 degrees C
relative to the surrounding Baltic Sea. Sampled fish ranged from young-of-the
year to 14 years. Geometric morphometrics and multivariate statistical analysis
revealed significant morphological differences between individuals of P.
fluviatilis from these two habitats. Most importantly, relative shape changed
with size, with small individuals of P. fluviatilis from Biotest being
characterized by a deeper body shape and a larger caudal peduncle than the
smaller Baltic individuals. In large specimens, smaller differences were found
with Biotest individuals being more slender than Baltic individuals. These
results show that, in order to have a full understanding of the biological
effects of elevated temperatures, studies that cover the entire size range of
organisms will be important. Apart from the direct influence of temperature on
growth rate and body shape, other ecological factors affected by temperature are
discussed as possible contributors to the observed differences between the two
populations.
PMID- 26440308
TI - Direct Air Capture of CO2 by Physisorbent Materials.
AB - Sequestration of CO2, either from gas mixtures or directly from air (direct air
capture, DAC), could mitigate carbon emissions. Here five materials are
investigated for their ability to adsorb CO2 directly from air and other gas
mixtures. The sorbents studied are benchmark materials that encompass four types
of porous material, one chemisorbent, TEPA-SBA-15 (amine-modified mesoporous
silica) and four physisorbents: Zeolite 13X (inorganic); HKUST-1 and Mg-MOF-74/Mg
dobdc (metal-organic frameworks, MOFs); SIFSIX-3-Ni, (hybrid ultramicroporous
material). Temperature-programmed desorption (TPD) experiments afforded
information about the contents of each sorbent under equilibrium conditions and
their ease of recycling. Accelerated stability tests addressed projected shelf
life of the five sorbents. The four physisorbents were found to be capable of
carbon capture from CO2-rich gas mixtures, but competition and reaction with
atmospheric moisture significantly reduced their DAC performance.
PMID- 26440309
TI - Active YAP promotes pancreatic cancer cell motility, invasion and tumorigenesis
in a mitotic phosphorylation-dependent manner through LPAR3.
AB - The transcriptional co-activator Yes-associated protein, YAP, is a main effector
in the Hippo tumor suppressor pathway. We recently defined a mechanism for
positive regulation of YAP through CDK1-mediated mitotic phosphorylation. Here,
we show that active YAP promotes pancreatic cancer cell migration, invasion and
anchorage-independent growth in a mitotic phosphorylation-dependent manner.
Mitotic phosphorylation is essential for YAP-driven tumorigenesis in animals. YAP
reduction significantly impairs cell migration and invasion. Immunohistochemistry
shows significant upregulation and nuclear localization of YAP in metastases when
compared with primary tumors and normal tissue in human. Mitotic phosphorylation
of YAP controls a unique transcriptional program in pancreatic cells. Expression
profiles reveal LPAR3 (lysophosphatidic acid receptor 3) as a mediator for
mitotic phosphorylation-driven pancreatic cell motility and invasion. Together,
this work identifies YAP as a novel regulator of pancreatic cancer cell motility,
invasion and metastasis, and as a potential therapeutic target for invasive
pancreatic cancer.
PMID- 26440310
TI - Targeted massively parallel sequencing of angiosarcomas reveals frequent
activation of the mitogen activated protein kinase pathway.
AB - Angiosarcomas are rare malignant mesenchymal tumors of endothelial
differentiation. The clinical behavior is usually aggressive and the prognosis
for patients with advanced disease is poor with no effective therapies. The
genetic bases of these tumors have been partially revealed in recent studies
reporting genetic alterations such as amplifications of MYC (primarily in
radiation-associated angiosarcomas), inactivating mutations in PTPRB and R707Q
hotspot mutations of PLCG1. Here, we performed a comprehensive genomic analysis
of 34 angiosarcomas using a clinically-approved, hybridization-based targeted
next-generation sequencing assay for 341 well-established oncogenes and tumor
suppressor genes. Over half of the angiosarcomas (n = 18, 53%) harbored genetic
alterations affecting the MAPK pathway, involving mutations in KRAS, HRAS, NRAS,
BRAF, MAPK1 and NF1, or amplifications in MAPK1/CRKL, CRAF or BRAF. The most
frequently detected genetic aberrations were mutations in TP53 in 12 tumors(35%)
and losses of CDKN2A in9 tumors (26%). MYC amplifications were generally mutually
exclusive of TP53 alterations and CDKN2A loss and were identified in 8 tumors
(24%), most of which (n = 7, 88%) arose post-irradiation. Previously reported
mutations in PTPRB (n = 10, 29%) and one (3%) PLCG1 R707Q mutation were also
identified. Our results demonstrate that angiosarcomas are a genetically
heterogeneous group of tumors, harboring a wide range of genetic alterations. The
high frequency of genetic events affecting the MAPK pathway suggests that
targeted therapies inhibiting MAPK signaling may be promising therapeutic avenues
in patients with advanced angiosarcomas.
PMID- 26440311
TI - Molecular targeting of protein arginine deiminases to suppress colitis and
prevent colon cancer.
AB - Ulcerative colitis (UC) is a chronic disease, in which the lining of the colon
becomes inflamed and develops ulcers leading to abdominal pain, diarrhea, and
rectal bleeding. The extent of these symptoms depends on disease severity. The
protein arginine deiminase (PAD) family of enzymes converts peptidyl-Arginine to
peptidyl-Citrulline through citrullination. PADs are dysregulated, with abnormal
citrullination in many diseases, including UC and colorectal cancer (CRC). We
have developed the small molecule, pan-PAD inhibitor, Chlor-amidine (Cl-amidine),
with multiple goals, including treating UC and preventing CRC. Building off our
recent results showing that: 1) Cl-amidine suppresses colitis in vivo in a
dextran sulfate sodium (DSS) mouse model; and 2) Cl-amidine induces microRNA
(miR)-16 in vitro causing cell cycle arrest, we tested the hypothesis that Cl
amidine can prevent tumorigenesis and that miR-16 induction, by Cl-amidine, may
be involved in vivo. Consistent with our hypothesis, we present evidence that Cl
amidine, delivered in the drinking water, prevents colon tumorigenesis in our
mouse model of colitis-associated CRC where mice are given carcinogenic
azoxymethane (AOM), followed by multiple cycles of 2% DSS to induce colitis. To
begin identifying mechanisms, we examined the effects of Cl-amidine on miR-16.
Results show miR-16 suppression during the colitis-to-cancer sequence in colon
epithelial cells, which was rescued by drinking Cl-amidine. Likewise, Ki67 and
cellular proliferation targets of miR-16 (Cyclins D1 and E1) were suppressed by
Cl-amidine. The decrease in cell proliferation markers and increase in tumor
suppressor miRNA expression potentially define a mechanism of how Cl-amidine is
suppressing tumorigenesis in vivo.
PMID- 26440313
TI - Identification of the HrpS binding site in the hrpL promoter and effect of the
RpoN binding site of HrpS on the regulation of the type III secretion system in
Erwinia amylovora.
AB - The type III secretion system (T3SS) is a key pathogenicity factor in Erwinia
amylovora. Previous studies have demonstrated that the T3SS in E. amylovora is
transcriptionally regulated by an RpoN-HrpL sigma factor cascade, which is
activated by the bacterial alarmone (p)ppGpp. In this study, the binding site of
HrpS, an enhancer binding protein, was identified for the first time in plant
pathogenic bacteria. Complementation of the hrpL mutant with promoter deletion
constructs of the hrpL gene and promoter activity analyses using various lengths
of the hrpL promoter fused to a promoter-less green fluorescent protein (gfp)
reporter gene delineated the upstream region for HrpS binding. Sequence analysis
revealed a dyad symmetry sequence between -138 and -125 nucleotides (TGCAA-N4
TTGCA) as the potential HrpS binding site, which is conserved in the promoter of
the hrpL gene among plant enterobacterial pathogens. Results of quantitative real
time reverse transcription-polymerase chain reaction (qRT-PCR) and
electrophoresis mobility shift assay coupled with site-directed mutagenesis (SDM)
analysis showed that the intact dyad symmetry sequence was essential for HrpS
binding, full activation of T3SS gene expression and virulence. In addition, the
role of the GAYTGA motif (RpoN binding site) of HrpS in the regulation of T3SS
gene expression in E. amylovora was characterized by complementation of the hrpS
mutant using mutant variants generated by SDM. Results showed that a Y100F
substitution of HrpS complemented the hrpS mutant, whereas Y100A and Y101A
substitutions did not. These results suggest that tyrosine (Y) and phenylalanine
(F) function interchangeably in the conserved GAYTGA motif of HrpS in E.
amylovora.
PMID- 26440312
TI - Detection of cancer through exhaled breath: a systematic review.
AB - BACKGROUND: Timely diagnosis of cancer represents a challenging task; in
particular, there is a need for reliable non-invasive screening tools that could
achieve high levels of adherence at virtually no risk in population-based
screening. In this review, we summarize the current evidence of exhaled breath
analysis for cancer detection using standard analysis techniques and electronic
nose. METHODS: Relevant studies were identified searching Pubmed and Web of
Science databases until April 30, 2015. Information on breath test performance,
such as sensitivity and specificity, was extracted together with volatile
compounds that were used to discriminate cancer patients from controls.
Performance of different breath analysis techniques is provided for various
cancers together with information on methodological issues, such as breath
sampling protocol and validation of the results. RESULTS: Overall, 73 studies
were included, where two-thirds of the studies were conducted on lung cancer.
Good discrimination usually required a combination of multiple biomarkers, and
area under the receiver operating characteristic curve or accuracy reached levels
of 0.9 or higher in multiple studies. In 25% of the reported studies,
classification models were built and validated on the same datasets. Huge
variability was seen in different aspects among the studies. CONCLUSIONS:
Analyses of exhaled breath yielded promising results, although standardization of
breath collection, sample storage and data handling remain critical issues. In
order to foster breath analysis implementation into practice, larger studies
should be implemented in true screening settings, paying particular attention to
standardization in breath collection, consideration of covariates, and validation
in independent population samples.
PMID- 26440315
TI - Achieving crop stress tolerance and improvement--an overview of genomic
techniques.
AB - The inexorable exposure of plants to the combinations of abiotic stresses has
affected the worldwide food supply. The crop improvement against these abiotic
stresses has been captivating approach to increase the yield and enhance the
stress tolerance. By using traditional and modern breeding methods, the
characters that confer tolerance to these stresses were accomplished. No doubt
genetic engineering and molecular breeding have helped in comprehending the
intricate nature of stress response. Understanding of abiotic stress-involved
cellular pathways provides vital information on such responses. On the other
hand, genomic research for crop improvement has raised new assessments in
breeding new varieties against abiotic stresses. Interpretation of responses of
the crop plants under stress is of great significance by studying the main role
of crops in food and biofuel production. This review presents genomic-based
approaches revealing the complex networks controlling the mechanisms of abiotic
stress tolerance, and the possible modes of assimilating information attained by
genomic-based approaches due to the advancement in isolation and functional
analysis of genes controlling the yield and abiotic stress tolerance are
discussed.
PMID- 26440314
TI - Assessment of Antioxidant Enzyme Activity and Mineral Nutrients in Response to
NaCl Stress and its Amelioration Through Glutathione in Chickpea.
AB - Salinity stress has been reckoned as one of the major threat towards crop
productivity as it causes significant decline in the yield. The impact of NaCl
stress (0, 1, 10, 50, 100 and 200 mg L(-1)) as well as glutathione (10 mg L(-1))
either alone or in combination has been evaluated on the induction of multiple
shoots, antioxidant enzymes' activity, lipid peroxidation, relative permeability,
concentration of nutrients, photosynthetic pigments, protein and proline content
of nodal segments of chickpea after 14 days of culture. The antioxidant enzyme
activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase
(APX), guaiacol peroxidase (GPX) and glutathione reductase (GR) were found to be
increased under salt stress as well as glutathione-supplemented medium. A
significant decrease in the concentrations of chlorophylls a, b, total
chlorophyll and carotenoid was observed under salt stress. Concentrations of
nitrogen, phosphorus, potassium, calcium, carbon, magnesium and sulphur showed an
initial increase up to 10 mg L(-1) NaCl, but a decline was seen at higher NaCl
levels. Proline content and malondialdehyde concentration were found to be
increased under salt stress. Three isoforms of SOD, one of CAT and four of GPX
were expressed during native polyacrylamide gel electrophoresis (PAGE) analysis.
However, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of
the stressed nodal explants revealed the over-expression of several polypeptide
bands related to NaCl stress. These findings for the first time suggest that
glutathione (GSH) helps in ameliorating NaCl stress in nodal explants of chickpea
by manipulating various biochemical and physiological responses of plants.
PMID- 26440316
TI - Effect of predictability on the stress response to chasing in Atlantic salmon
(Salmo salar L.) parr.
AB - The possibility to prepare for and respond to challenges in a proper manner is
essential to cope with a changing environment, and learning allows fish to up or
downregulate the stress response based on experience. The regulation of the
response to predicted needs should be easier in more predictable environments. We
exposed salmon parr to chasing of either 15 s (weak stressor) or 5 min (strong
stressor) twice daily for a 7-day learning period, with chasing either announced
by a 30 s light signal (conditioned) or not announced (unconditioned). The
behavioural response to the light signal was different between the conditioned
and unconditioned groups, demonstrating that conditioned groups associated the
signal with chasing. We could, however, not demonstrate any effect on the stress
response of anticipation. The fish habituated to repeated stress exposures with a
similar decrease in oxygen hyperconsumption in all groups. Due to habituation,
possible effects of predictable announcement of a stressor on the physiological
stress response may not have been expressed in this study. Plasma cortisol
concentrations 1h after light signal and chasing the day after the training
period was moderate in all groups although higher after 5 min chasing (13 ng ml(
1)) than 15 s chasing (7 ng ml(-1)). There was no physiological stress response
after exposure to the light signal only after the learning period. We argue that
the benefit of predictability of stressors is limited when the fish have no way
to avoid the stressor.
PMID- 26440317
TI - Temporal discounting rates and their relation to exercise behavior in older
adults.
AB - As our nation's population ages, the rates of chronic illness and disability are
expected to increase significantly. Despite the knowledge that exercise may
prevent chronic disease and promote health among older adults, many still are
inactive. Factors related to exercise behaviors have been explored in recent
years. However, temporal discounting is a motivational concept that has not been
explored in regard to exercise in older adults. Temporal discounting is a
decision making process by which an individual chooses a smaller more immediate
reward over a larger delayed reward. The aim of this study was to determine if
temporal discounting rates vary between exercising and non-exercising older
adults. DESIGN: This study used cross-sectional survey of 137 older adults living
in the community. Older adults were recruited from 11 rural Arkansas churches.
The Kirby delay-discounting Monetary Choice Questionnaire was used to collect
discounting rates and then bivariate analysis was performed to compare temporal
discounting rate between the exercisers and non-exercisers. Finally, multivariate
analysis was used to compare discounting rate controlling for other covariates.
RESULTS: The results indicated that exercising older adults display lower
temporal discounting rates than non-exercising older adults. After controlling
for education, exercisers still have lower temporal discounting rates than non
exercisers (p<0.001). CONCLUSIONS AND IMPLICATIONS: These findings are important
as several chronic health conditions relate to lack of exercise especially in
older adults. This research suggests that if we can find appropriate incentives
for discounting individuals, some type of immediate reward, then potentially we
can design programs to engage and retain older adults in exercise.
PMID- 26440318
TI - Behavioral characterization of a model of differential susceptibility to obesity
induced by standard and personalized cafeteria diet feeding.
AB - Despite the increase in obesity prevalence over the last decades, humans show
large inter-individual variability for susceptibility to diet-induced obesity.
Understanding the biological basis of this susceptibility could identify new
therapeutic alternatives against obesity. We characterized behavioral changes
associated with propensity to obesity induced by cafeteria (CAF) diet consumption
in mice. We show that Balb/c mice fed a CAF diet display a large inter-individual
variability in susceptibility to diet-induced obesity, such that based on changes
in adiposity we can classify mice as obesity prone (OP) or obesity resistant
(OR). Both OP and OR were hyperphagic relative to control-fed mice but caloric
intake was similar between OP and OR mice. In contrast, OR had a larger increase
in locomotor activity following CAF diet compared to OP mice. Obesity resistant
and prone mice showed similar intake of sweet snacks, but OR ate more savory
snacks than OP mice. Two bottle sucrose preference tests showed that OP decreased
their sucrose preference compared to OR mice after CAF diet feeding. Finally, to
test the robustness of the OR phenotype in response to further increases in
caloric intake, we fed OR mice with a personalized CAF (CAF-P) diet based on
individual snack preferences. When fed a CAF-P diet, OR increased their calorie
intake compared to OP mice fed the standard CAF diet, but did not reach adiposity
levels observed in OP mice. Together, our data show the contribution of hedonic
intake, individual snack preference and physical activity to individual
susceptibility to obesity in Balb/c mice fed a standard and personalized
cafeteria-style diet.
PMID- 26440320
TI - BEEF SPECIES SYMPOSIUM: Making more but using less: The future of the U.S. beef
industry with a reduced cow herd and the challenge to feed the United States and
world.
PMID- 26440319
TI - Changes in jaw muscle activity and the physical properties of foods with
different textures during chewing behaviors.
AB - This study aimed to investigate how the activity of the masseter (Mas) and
suprahyoid (Hyoid) muscles is influenced by the physical properties of food, how
changes in the rheological properties of food differ between different foods
during the process of food reduction, and how different salivary flow rates
affect bolus-making capability during masticatory behavior in healthy humans. Ten
healthy adults participated in this study. Electromyographic (EMG) recordings
were obtained from the Mas and Hyoid muscles, and 15 g of steamed rice and rice
cake was prepared as test foods. In the ingestion test, the subjects were asked
to eat each food in their usual manner. The chewing duration, number of chewing
cycles before the first swallow, Mas and Hyoid EMG activity, and chewing cycle
time were compared between the foods. Total chewing duration was divided into
three substages: early, middle, and late; chewing cycle time and EMG activity per
chewing cycle of each substage were compared between the foods and among the
substages. In the spitting test, the rheological properties of the bolus at the
end of each substage were compared between the foods and among the substages.
Finally, stimulated salivary flow rates were measured and the relationships
between salivary flow rate and chewing duration, EMG activity, and changes in
physical food characteristics were investigated. There were significant
differences in total chewing duration and the number of chewing cycles, but not
in chewing cycle time, between the foods, which had similar hardness values. The
EMG activity levels of the Mas and Hyoid per chewing cycle for the rice cake were
significantly greater than for the steamed rice throughout the recording periods.
While Mas activity did not change among the substages during chewing, Hyoid EMG
activity decreased as chewing progressed. Chewing cycle time also gradually
decreased as chewing progressed. The hardness of both foods initially increased,
then gradually decreased back to baseline. The adhesiveness of the rice cake
initially increased, and did not fall throughout the recording period; the
adhesiveness of the steamed rice did not significantly change. Cohesiveness
barely changed in either of the two foods during chewing, but was significantly
greater for the rice cake than for the steamed rice. Finally, a correlation
between the stimulated salivary flow rate and chewing performance was evident
only in a change in Mas EMG activity. The current results demonstrate that the
activities of the Mas and Hyoid muscles changed as chewing progressed, and were
affected by hardness, adhesiveness, and cohesiveness. Salivary flow rate may
affect the changes in Mas activity during the process of bolus formation.
PMID- 26440321
TI - BEEF SPECIES SYMPOSIUM: Economic considerations related to U.S. beef herd
expansion.
AB - Significant attention perpetually surrounds possible changes in breeding herd
inventories in the U.S. beef cattle industry. This article outlines economic
considerations of U.S. herd expansion. Factors restricting expansion include land
availability, increasing production efficiency, operator demographics, capital
requirements, and commodity price volatility. Several offsetting factors support
herd expansion including unprecedented cow-calf returns, ongoing global beef
demand growth, and timing within the current cattle cycle. In addition to these
industry-wide factors, several important variations in individual ranch
considerations are outlined. The authors' expectations on future herd dynamics
are provided, highlighting broader implications for individual operations,
industry leaders, and the entire beef-cattle supply chain. The substantial
economic impact and importance of the cow-calf sector warrants broader
appreciation of these economic factors impacting herd expansion. The future size
of the U.S. cattle industry is determined by the individual decisions of over
70,000 cattle owners, making this issue worthy of review by all industry
stakeholders.
PMID- 26440322
TI - BEEF SPECIES SYMPOSIUM: Can we build the cowherd by increasing longevity of
females?
AB - Increasing longevity of beef cows by decreasing the proportion culled due to
reproductive failure provides an efficient process to rebuild a cow herd and can
reduce number of replacements needed to sustain a constant herd size. Rate of
reproductive failure varies due to cow age, where failure in cows 2 to 4 yr of
age is often greater than in cows 5 to 7 yr of age. In addition, BW of cow and
calf at weaning increase as cows advance from 2 to 5 yr of age. The cumulative
effect of increasing retention of young cows is improved production efficiency
through decreased replacement rate and changing age structure of the herd
resulting in a greater proportion of cows at maximal production potential for
calf BW at weaning and cow BW at time of culling. Calculations from cow age
specific culling and BW data from commercial and research herds indicated that
reducing replacement rate from 18% to 14% resulted in a 23% increase in calf BW
weaned and a 2% increase in cull cow BW per pregnant replacement heifer going
into the herd. Although improving longevity increases production efficiency,
genetic advancement in sustained reproductive function is challenging, as it is
the sequential culmination of the annual repetition of numerous discrete
physiological processes, each ending in a qualitative response. Successful
completion of one process is prerequisite to evaluating subsequent processes.
These physiological processes are subject to nutritional threshold requirements
that may vary due to genetic potential for other production traits such as milk,
growth, and mature size resulting in genetic-by-nutrition interactions. This is
in contrast to most traits for which EPD exist, where genetic-by-environment
interactions are not considered to be significant. Extensive research concerning
impact of limited nutrition on reproduction has led to recommendations that
heifers and cows be fed to a threshold BW or BCS to ensure reproductive success;
a process that masks nutritional interactions that might otherwise result in
reproductive failure. This management approach minimizes selection for animals
capable of sustained reproductive function under limited nutritional
environments. Rearing and managing cows under nutritionally limited environments
may lead to adaptations that result in relatively high levels of reproductive
success under lower input levels. Such adaptation may improve chances for longer
retention in their offspring in nutrient-limited environments.
PMID- 26440323
TI - BEEF SPECIES SYMPOSIUM: Beef production without mature cows.
AB - Nutrients in animal feed get partitioned to growth, lactation, pregnancy, fat
accretion, and/or maintenance. For mature beef cows, >80% of nutrients consumed
annually go to unproductive maintenance. Integrated over the entire U.S. beef
cattle production system, nearly one-half of the nutrients consumed go to
maintenance of cow herds. This accounts for much of the inefficiency of beef
production and can be minimized by the single-calf heifer system, in which
heifers are fattened and slaughtered after having their first calf. We propose a
modification, use of sexed semen, so that most heifers replace themselves with a
heifer calf. This greatly decreases the size of the inherently inefficient cow
herd required for beef production and greatly increases efficiency of beef
production in terms of nutrients consumed and waste produced, such as methane, by
increasing the ratio of nutrients used for growth to those used for maintenance.
Additional management is required including AI, early weaning, and the attention
required when calving 2-yr-old heifers. Low conception rates with sexed semen and
less efficient growth of females than males also must be considered. However,
these issues seem greatly outweighed by the benefits of increased efficiency from
decreasing cow herd size while eliminating the need for breeding back lactating
first-calf heifers, the need for castration, and health problems inherent in
older cows such as mastitis and lameness. Moreover, the decreased generation
interval can greatly accelerate genetic progress.
PMID- 26440324
TI - Sex impact on the quality of fatty liver and its genetic determinism in mule
ducks.
AB - Recent changes to French regulations now allow farmers to produce "foie gras"
from both male and female mule ducks. The aim of this study was to assess the
quality of female fatty liver and to compare, from a phenotypic and genetic point
of view, liver quality in males and females. A total of 914 mule ducks (591 males
and 323 females), hatched in a single pedigree batch, were reared until 86 d of
age and then force-fed for 12 d, before being slaughtered. Carcasses and livers
were weighed and liver quality was assessed by grading the extent of liver
veining and measuring the liver melting rate, either after sterilization of 60 g
of liver or pasteurization of 180 g of liver. Sexual dimorphism was observed in
favor of males, with a difference of approximately 10% in carcass and liver
weights and up to 54% for the liver melting rate. Moreover, one-third of female
livers showed moderate to high veining, whereas this was not the case for male
livers. The fatty livers of female mule ducks are, therefore, of poorer quality
and could not be transformed into a product with the appellation "100% fatty
liver." According to sex and parental line, heritability values ranged from 0.12
+/- 0.05 to 0.18 +/- 0.07 for fatty liver weight and from 0.09 +/- 0.05 to 0.18
+/- 0.05 for the 2 melting rate traits. The genetic correlations between the
fatty liver weight and both melting rates were high (greater than +0.80) in the
Muscovy population, whereas in the Pekin population, the liver weight and melting
rates were less strongly correlated (estimates ranging from +0.36 +/- 0.30 to
+0.45 +/- 0.28). Selection for lower liver melting rates without reducing the
liver weight would, therefore, be easier to achieve in the Pekin population.
Finally, as the 2 melting rate measurements are highly correlated (0.91 and over
0.95 for phenotypic and genetic correlations, respectively), we suggest using the
easiest method, that is, sterilization of 60 g of liver.
PMID- 26440325
TI - Characterization and functional analysis of porcine estrogen-related receptors
and their alternative splicing variants.
AB - Estrogen-related receptors (ESRR) are orphan nuclear hormone receptors with
unidentified ligands; they play important roles in tissue regulation and
development and maintenance of pluripotent cell identity. The splicer variant,
genomic organization, and physiological roles of ESRR have been elucidated in the
human and the mouse. However, in livestock, they remain elusive. In this study,
we cloned porcine ESRR family members , , and . Two alternative splicing
variants, and , and a novel were identified. To determine the domain function, we
constructed vectors with sequential deletions of the ESRRB coding sequence. The
functional analysis showed that the C domain of ESRR plays a core role in
promoting the activation of estrogen response elements that are found in all
kinds of ESRR-targeting genes, whereas the E domain is not essential for
transcription regulation of ESRR unless a specific and identified ligand is
applied.
PMID- 26440326
TI - Estimates of genetic parameters for content of boar taint compounds in adipose
tissue of intact males at 160 and 220 days of age.
AB - The aims of this study were to investigate variation in content of androstenone
(AND), skatole (SKA), and indole (IND), quantified in adipose tissue of intact
male pigs at 160 d of age (105 kg BW) and 220 d of age (155 kg BW), to estimate
genetic parameters and to investigate the genetic relationships for AND, SKA,
IND, and growth traits. A sample of adipose tissue was collected in vivo, using a
biopsy device, from the neck of 500 intact males at the 2 ages and at slaughter
from the ham of 100 of the investigated animals. Backfat depth was measured at
220 d of age, whereas BW was recorded at each sampling. Quantification of AND,
SKA, and IND was performed by HPLC with fluorescence detection. Estimates of
genetic parameters were obtained through Bayesian analyses after logarithmic
transformations of original measures. Contents of boar taint compounds (BTC)
measured at 220 d were higher than those at 160 d of age. Correlations between
contents of BTC in backfat and ham fat ranged from 0.7 (IND) to 0.88 (SKA).
Medium-high h were estimated for BTC at both ages, but estimates at 220 d (0.58,
0.60, and 0.69 for AND, SKA, and IND, respectively) were greater than those at
160 d. The genetic correlation between contents at 160 and 220 d of each BTC was
positive, but the probability that such estimates were greater than 0.8 was very
low, indicating that contents at 160 and 220 d were traits controlled by
different genetic backgrounds. Different rankings were observed when breeding
values for the content at 160 and 220 d of age were used to rank animals. As a
consequence, performance testing programs for BTC should be based preferably on
phenotypes measured at 220 d of age. Weak genetic correlations were observed
between content of BT compounds and growth traits (BW, backfat depth, and daily
gain from 160 to 220 d of age), indicating that selective breeding to reduce the
risk of tainted pork is expected to exert trivial effects on growth performance
and fat deposition. Results indicate that prevalence of BTC is high in mature and
heavy pigs relative to young and light pigs. High heritability; positive genetic
correlations between AND, SKA, and IND; and trivial effects on growth traits
suggest that reduction of BTC through selective breeding is feasible and
exploitable as an alternative to surgical castration also for pigs slaughtered at
heavy BW.
PMID- 26440327
TI - Genetic parameters for large-scale behavior traits and type traits in Charolais
beef cows.
AB - In the last decades, beef cattle breeding mainly focused on improving production
and reproduction traits. Nowadays, there is a growing interest to include
behavior and type traits in the breeding goal. There is an interest in behavior
as it is associated with human safety and workability and in type traits as they
might be associated with longevity of cows. The objective of the current study
was to estimate the heritability for behavior and type traits in Charolais and to
estimate the genetic correlations among these traits. Behavior traits, including
aggressiveness at parturition, aggressiveness during gestation period, and
maternal care, were scored by farmers using an on-farm recording system to enable
large-scale collection of phenotypes. Type traits, including udder traits ( = 3),
teat traits (3), feet and leg traits (5), and locomotion (1), were scored by 10
trained classifiers. Data was available on 6,649 cows in parity 1 to 12 and
located in 380 herds. Results showed that differences between herds explained up
to 23% of the total phenotypic variance in behavior traits. This might be due to
differences in management or to consistent differences in scoring between
farmers. Aggressiveness at parturition had higher heritability (0.19) and higher
genetic coefficient of variation (CV = 11%) than aggressiveness during gestation
( = 0.06 and CV = 4%) and maternal care ( = 0.02 and CV = 2%). Heritabilities for
udder traits (0.14 to 0.20) and teat traits (0.17 to 0.35) were higher than for
feet and leg traits (0.02 to 0.19). Genetic coefficients of variation for udder
and teat traits were also higher (up to 21%) than for feet and leg traits (up to
11%). Strong genetic correlations were found between behavior traits (with
absolute values from 0.71 to 0.98). The genetic correlations indicate that it is
difficulty to simultaneously improve maternal care and reduce aggressiveness. We
concluded that there are good opportunities to implement selection for improved
udder and teat traits and against aggressiveness at parturition using a simple on
farm recording system of behavior.
PMID- 26440328
TI - Description of the growth curve for Angus pasture-fed cows under extensive
systems.
AB - Growth curves are useful for describing the sigmoid shape of an animal's weight
pattern over time. The purpose of the present study was to describe, for the
first time, a complete growth curve for pasture-fed Angus cows in Uruguay and to
analyze the major fixed effects that affect the estimation of mature cow weight
(CW). A total of 22,743 records from 5,284 cows belonging to 73 herds were used
in the statistical analysis. Five nonlinear models (Brody, Gompertz, Von
Bertalanffy, logistic, and Richards) and a 3-knot cubic spline function were
fitted to model weight change across age. Body weights were recorded at birth,
weaning, and 18 mo and as an adult (at 2.3-3.6, 3.6-4.6, 4.6 to 5.6, 5.6 to 6.6,
and 6.6 to 8.1 yr). After preliminary analyses, the fixed effects included in the
model to estimate CW were BCS, herd, year and month of measurement, and age of
dam. The herd and BCS were the major significant sources of variation. The
Richards model had the lowest values for Akaike information criterion, Bayesian
information criterion, and -2 log likelihood, with the asymptotic weight being
542 kg. The spline function was the model that fitted the data most closely to
the observed weights followed by the Richards function. The Richards model gave
better predictions of weights from birth to maturity than the other 4 nonlinear
models, because these functions were shown to over- or underestimate weights at
different ages in this beef cattle data set. The predicted curve showed that cows
reach mature CW after 5 yr of age, which is the age commonly assumed as adult
weight in beef cattle. Results form this analysis allowed the estimation of CW
and rate of maturing and to take knowledge of the shape of growth curve for Angus
females in Uruguay under extensive conditions, helping breeders to take selection
decisions. In this way, breeders can optimize the management and efficiency for
each production system.
PMID- 26440329
TI - Role of G protein-coupled receptors (GPCR), matrix metalloproteinases 2 and 9
(MMP2 and MMP9), heparin-binding epidermal growth factor-like growth factor
(hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth
factor 1 receptor (IGF-1R) in trenbolone acetate-stimulated bovine satellite cell
proliferation.
AB - Implanting cattle with steroids significantly enhances feed efficiency, rate of
gain, and muscle growth. However, the mechanisms responsible for these
improvements in muscle growth have not been fully elucidated. Trenbolone acetate
(TBA), a testosterone analog, has been shown to increase proliferation rate in
bovine satellite cell (BSC) cultures. The classical genomic actions of
testosterone have been well characterized; however, our results indicate that TBA
may also initiate a quicker, nongenomic response that involves activation of G
protein-coupled receptors (GPCR) resulting in activation of matrix
metalloproteinases 2 and 9 (MMP2 and MMP9) that release membrane-bound heparin
binding epidermal growth factor-like growth factor (hbEGF), which then binds to
and activates the epidermal growth factor receptor (EGFR) and/or erbB2.
Furthermore, the EGFR has been shown to regulate expression of the IGF-1 receptor
(IGF-1R), which is well known for its role in modulating muscle growth. To
determine whether this nongenomic pathway is potentially involved in TBA
stimulated BSC proliferation, we analyzed the effects of treating BSC with
guanosine 5'-O-2-thiodiphosphate (GDPbetaS), an inhibitor of all GPCR; a MMP2 and
MMP9 inhibitor (MMPI); CRM19, a specific inhibitor of hbEGF; AG1478, a specific
EGFR tyrosine kinase inhibitor; AG879, a specific erbB2 kinase inhibitor; and
AG1024, an IGF-1R tyrosine kinase inhibitor on TBA-stimulated proliferation rate
(H-thymidine incorporation). Assays were replicated at least 9 times for each
inhibitor experiment using BSC cultures obtained from at least 3 different
animals. Bovine satellite cell cultures were obtained from yearling steers that
had no previous exposure to androgenic or estrogenic compounds. As expected, BSC
cultures treated with 10 n TBA showed ( < 0.05) increased proliferation rate when
compared with control cultures. Additionally, treatment with 5 ng hbEGF/mL
stimulated proliferation in BSC cultures ( < 0.05). Treatment with GDPbetaS,
MMPI, CRM197, AG1024, AG1478, and/or AG879 all suppressed ( < 0.05) TBA-induced
increases in proliferation. These data indicate that TBA likely initiates a
nongenomic response involving GPCR, MMP2 and MMP9, hbEGF, EGFR, erbB2, and IGF
1R, which may play a role in TBA-mediated increases in BSC proliferation.
PMID- 26440330
TI - Coordinated gene expression between skeletal muscle and intramuscular adipose
tissue in growing beef cattle.
AB - Previous research indicates that metabolism and fiber type of skeletal muscle is
related to intramuscular lipid content. It is hypothesized that changes in
skeletal muscle gene expression influence adipose tissue development. The
objective of this study was to determine differences in the metabolism and
intercellular signaling of skeletal muscle fibers within the same muscle group
that could be responsible for the initiation of intramuscular adipose tissue
development and differentiation. Longissimus dorsi muscle samples were collected
from steers ( = 12; 385 d of age; 378 kg BW) grazing wheat pasture. Longissimus
muscle samples were dissected under magnification and sorted into 3 categories
based on visual stage of adipose tissue development: immature intramuscular
adipose tissue (MM), intermediate intramuscular adipose tissue (ME), and mature
intramuscular adipose tissue (MA). Additionally, muscle fibers lying adjacent to
each intramuscular adipose tissue (IM) category and those not associated with IM
tissue were collected and stored separately. Quantitative real-time PCR was used
to determine relative fold change in genes involved in metabolism, angiogenesis,
formation of extracellular matrix, and intercellular signaling pathways in both
LM and IM samples. Gene expression data were analyzed using a GLM that included
the fixed effect of tissue. Pearson correlation coefficients were also computed
between gene expression in LM and IM tissue samples that were at the same stage
of development. and gamma mRNA expression were 3.56- and 1.97-fold greater ( <
0.05) in ME and MA IM compared with MM IM whereas mRNA expression was 1.43-fold
less ( < 0.01) in MA IM compared with MM IM, indicating successful separation
into different development categories. Genes associated with metabolism and
angiogenesis in LM tissue showed no differences among stages of development.
Myostatin expression did not change in LM tissue; however, expression of and mRNA
decreased ( < 0.01) as IM matured. and mRNA expression were 2.5- and 1.32-fold
greater in LM associated with MM IM than in LM associated with ME IM. Angiogenic
growth factors in MM IM tissue had a strong positive correlation ( >= 0.69) with
angiogenic growth factors in LM associated with MM IM; however, no correlation
was observed in ME or MA IM. These data indicate a coordinated effort between LM
and IM in early stages of IM development.
PMID- 26440331
TI - In utero heat stress increases postnatal core body temperature in pigs.
AB - In utero heat stress (IUHS) negatively impacts postnatal development, but how it
alters future body temperature parameters and energetic metabolism is not well
understood. Future body temperature indices and bioenergetic markers were
characterized in pigs from differing in utero thermal environments during
postnatal thermoneutral (TN) and cyclical heat stress (HS) exposure. First-parity
pregnant gilts ( = 13) were exposed to 1 of 4 ambient temperature (T) treatments
(HS [cyclic 28 degrees C to 34 degrees C] or TN [cyclic 18 degrees C to 22
degrees C]) applied for the entire gestation (HSHS, TNTN), HS for the first half
of gestation (HSTN), or HS for the second half of gestation (TNHS). Twenty-four
offspring (23.1 +/- 1.2 kg BW; = 6 HSHS, = 6 TNTN, = 6 HSTN, = 6 TNHS) were
housed in TN (21.7 degrees C +/- 0.7 degrees C) conditions and then exposed to 2
separate but similar HS periods (HS1 = 6 d; HS2 = 6 d; cycling 28 degrees C to 36
degrees C). Core body temperature (T) was assessed every 15 min with implanted
temperature recorders. Regardless of in utero treatment, T increased during both
HS periods ( = 0.01; 0.58 degrees C). During TN, HS1, and HS2, all IUHS pigs
combined had increased T ( = 0.01; 0.36 degrees C, 0.20 degrees C, and 0.16
degrees C, respectively) compared to TNTN controls. Although unaffected by in
utero environment, the total plasma thyroxine to triiodothyronine ratio was
reduced ( = 0.01) during HS1 and HS2 (39% and 29%, respectively) compared with
TN. In summary, pigs from IUHS maintained an increased T compared with TNTN
controls regardless of external T, and this thermal differential may have
practical implications to developmental biology and animal bioenergetics.
PMID- 26440332
TI - Effect of xylanases on ileal viscosity, intestinal fiber modification, and
apparent ileal fiber and nutrient digestibility of rye and wheat in growing pigs.
AB - Two experiments were performed to study the effect of xylanase on ileal extract
viscosity, in vivo fiber solubilization and degradation, and apparent ileal
digestibility (AID) of fiber constituents, OM, CP, starch, and crude fat in rye
and wheat in ileal-cannulated pigs. In Exp. 1, coarse rye without (NX) or with
addition of xylanase from Aspergillus niger (AN), (BS), or (TR) was fed to 8
ileal-cannulated barrows (initial BW 30.9 +/- 0.3 kg) for 1 wk each according to
a double 4 * 4 Latin square design. In Exp. 2, fine rye, fine wheat, and coarse
wheat with or without a combination of xylanase from and were fed to 6 ileal
cannulated barrows (initial BW 33.6 +/- 0.5 kg) for 1 wk according to a 6 * 6
Latin square design with a 2 * 3 factorial arrangement of enzyme and cereal
matrix. Chromic oxide (0.2%) was used as an inert marker. Ileal effluent was
collected for 8 h on d 5 and 7 and pooled for analysis. In Exp. 1, TR reduced
intestinal viscosity of pigs fed rye from 9.3 mPa.s in the control diet (NX) to
6.0 mPa.s ( < 0.001), whereas AN and BS had no effect. None of the enzymes
changed the concentration of total arabinoxylan, high-molecular-weight
arabinoxylan (HMW-AX), or arabinoxylan oligosaccharides (AXOS) in the liquid
phase of digesta. In Exp. 2, the enzyme combination reduced intestinal viscosity
for all 3 cereal matrices ( < 0.05), but the viscosity was much higher with fine
rye (7.6 mPa.s) than with fine and coarse wheat (<1.7 mPa.s). Simultaneously, the
total concentration of arabinoxylan in the liquid phase of digesta increased by
82.4% in fine wheat ( < 0.002) and by 45.9% in coarse wheat ( < 0.006), and AXOS
increased 16-fold with enzyme addition. Similar effects of enzyme were not seen
with rye. The concentration of xylooligosaccharides in the liquid phase of
digesta increased with enzyme addition, but for xylose, it was only significant
for wheat, for which it increased 3.9-fold ( < 0.001). None of the xylanases
affected AID of arabinoxylan of rye in Exp. 1. In Exp. 2, the enzyme combination
increased AID of arabinoxylan by 91% to 107% ( < 0.001) across cereal matrices.
Enzyme addition did not affect AID of nutrients in any of the experiments except
for a higher starch and crude fat digestibility of fine wheat with enzyme
addition ( < 0.012) in Exp. 2. Collectively, the results suggest that xylanase is
more efficient in degrading arabinoxylan from wheat than from rye.
PMID- 26440333
TI - Effects of a multi-strain Bacillus species-based direct-fed microbial on growth
performance, nutrient digestibility, blood profile, and gut health in nursery
pigs fed corn-soybean meal-based diets.
AB - This experiment was conducted to investigate the effect of a spp.-based direct
fed microbial (DFM) on growth performance, apparent total tract digestibility
(ATTD), blood profile, intestinal histomorphology, and fecal gas emission in
piglets fed corn and soybean meal-based diets. The DFM product was based on 1
strain of and 2 strains of and formulated to supply 1.5 * 10 cfu/g of feed. A
total of 128 piglets ([Yorkshire * Landrace] * Duroc; 6.8 +/- 0.6 kg BW; weaning
age: 24 d) were housed in groups (4 pigs/pen, 2 barrows and 2 gilts) and fed
diets ( = 16) without or with DFM in a 2-phase feeding program: d 0 to 14 (phase
I) and 15 to 42 (phase II). Feed intake and BW were measured weekly. At the end
of each phase, samples for blood urea nitrogen (BUN), blood creatinine, ATTD, and
fecal noxious gas emission were taken. At termination, 12 piglets per treatment
were killed to access intestinal tissues for histomorphology. Overall, pigs fed
DFM had a greater ( < 0.05) G:F than pigs fed the control diet. In phase I, pigs
fed DFM showed a greater ( < 0.05) ADG and lower ( < 0.05) concentration of BUN
and fecal ammonia emission than the control group. In phase II, a greater ( <
0.05) ATTD of nitrogen and longer ( < 0.05) duodenum and jejunum villi were
observed in pigs fed the DFM diet compared with the control group. In conclusion,
inclusion of DFM improved growth performance and villi length of the duodenum and
jejunum in nursery pigs. Furthermore, DFM enhanced protein utilization as
demonstrated by increased nitrogen digestibility, lower BUN, and lower fecal
ammonia release.
PMID- 26440334
TI - Effects of stocking rate on forage nutrient composition of Nebraska Sandhills
upland range when grazed in early summer.
AB - Twelve 2-ha, Nebraska Sandhills upland range paddocks were used in a 2-yr study
to determine effects of stocking rate on grazed forage nutrient value in early
summer. Paddocks contain a mixture of native cool- and warm-season grasses with
forbs as a minor component. Stocking rates were 0 (control), 0.57 (light), and
0.85 (heavy) animal unit months per ha, respectively. Three esophageally
fistulated cows collected diet samples on May 14 (d 0), May 21 (d 7), May 28 (d
14), and June 4 (d 21) in 2013 and 2014. Ten quadrats per paddock were clipped
and separated into current or previous year growth on each diet sampling date.
All samples were analyzed for CP, NDF, and in vitro OM disappearance, which was
adjusted to an in vivo OM basis (). For diet samples, treatment interacted ( <
0.001) with sampling date for CP, NDF, and IVOMD. However, treatment and date did
not interact ( >= 0.32) for clipped samples. Diets collected in control paddocks
had greater ( < 0.05) IVOMD and CP and lower NDF compared with light and heavy
stocking rate paddocks on d 7, 14, and 21 but light stocking rate paddocks did
not differ ( >= 0.26) from heavy stocking rate paddocks on any sampling day
except d 21 NDF ( = 0.03). In general, previous year growth IVOMD, CP, and NDF
were not affected ( >= 0.11) by treatment. Generally, current year growth IVOMD
and CP were not affected ( >= 0.22) by treatment. Current year growth NDF did not
differ ( = 0.23) among stocking rates on d 0, but control paddock had lower ( =
0.02) NDF than light and heavy on d 7, 14, and 21. In stocked paddocks, diet
samples had greater ( < 0.01) IVOMD and CP and lower NDF than current and
previous year growth except IVOMD on d 0 where diet and current year growth did
not differ ( = 0.34). Generally, in control paddocks, current year growth and
diet samples had greater ( < 0.01) IVOMD and CP than previous year growth.
Control paddocks had greater ( < 0.01) forage accumulation than stocked paddocks
on d 7, 14, and 21; however, light and heavy stocked paddocks did not differ ( >=
0.29). On d 0 it was estimated that 96% of the diet was current year growth and
only 4% previous year growth, whereas on d 21, 70% of the diet was current year
growth vs. 30% previous year growth. Stocking pastures decrease current year
growth forage mass and therefore diet nutritive value by forcing cattle to
consume diets containing previous year growth in early summer.
PMID- 26440335
TI - Finishing performance of feedlot cattle fed condensed distillers solubles.
AB - Two experiments evaluated the effects of condensed distillers solubles (CDS) on
performance and carcass characteristics of finishing beef cattle. In Exp. 1, 250
crossbred steers (initial BW = 355 +/- 18 kg) were fed 0, 9, 18, 27, or 36% CDS
(DM basis) which replaced a portion of urea and a 1:1 ratio of dry-rolled corn
(DRC) and high-moisture corn (HMC). Steers were divided into 3 BW blocks and were
assigned randomly to 25 pens. Dietary fat increased from 3.7 to 9.4% as CDS
inclusion increased from 0 to 36%. Intake decreased linearly ( < 0.01) as CDS
increased. A quadratic response was observed for ADG ( = 0.01) and G:F ( < 0.01)
with maximum gain calculated at 20.8% CDS and maximum G:F at 32.5% CDS inclusion,
which was 12% more efficient than those fed 0% CDS. Experiment 2 was designed as
a 2 * 4 factorial using 400 crossbred steers (initial BW = 339 +/- 15 kg)
evaluating 0, 7, 14, or 21% CDS (DM basis) in 2 base byproduct diets containing
either 20% modified distillers grains plus solubles (MDGS) or 20% Synergy (a
blend of wet corn gluten feed and MDGS). Steers were divided into 2 BW blocks and
were assigned randomly to 40 pens. A tendency for a base diet * CDS inclusion
interaction was observed for ADG, HCW, and final BW ( < 0.10). Gain increased
linearly ( = 0.01) and tended to increase quadratically ( = 0.09) in MDGS diets,
with maximum calculated ADG at 16% CDS inclusion. Inclusion of CDS had no effect
on ADG in Synergy-based diets. Increasing CDS resulted in a linear increase in
G:F ( < 0.01) regardless of basal diet. Condensed distillers solubles may be
included in the diet at greater than 30% (DM basis) without other byproducts and
improve animal performance. Likewise, CDS can be fed in combination with other
byproduct feeds but with less improvement in performance.
PMID- 26440336
TI - Effects of roughage source and inclusion in beef finishing diets containing corn
wet distillers' grains plus solubles.
AB - Two experiments were conducted to determine the effects of roughage source and
inclusion in diets containing wet distillers' grains plus solubles (WDGS) on
finishing cattle performance and ruminal metabolism. In Exp. 1, 385 crossbred
steer calves (initial BW = 346 kg [SD 29]) were used in a finishing trial. A
control diet with no roughage inclusion was compared with 6 diets containing
either alfalfa hay (ALF), corn silage (CSIL), or corn stalks (CSTK) at 2
inclusions as a 3 * 2 factorial. Alfalfa hay was included at 4 (low) or 8%
(standard) of diet DM. Diets containing CSIL or CSTK were formulated to provide
total dietary NDF equal to the low and standard ALF inclusion diets. The final
diets contained 6.13 and 12.26% CSIL or 3.04 and 6.08% CSTK (DM basis). All diets
contained 30% WDGS and a 1:1 mixture of dry-rolled and high-moisture corn (DM
basis). Cattle fed no roughage had reduced ( < 0.01) DMI and tended ( <= 0.10) to
have the lowest final BW and ADG compared with cattle fed roughage. There were no
differences ( >= 0.11) in DMI, ADG, or G:F due to roughage source. Cattle fed a
standard inclusion of roughage had greater ( <= 0.04) DMI and ADG compared with
cattle fed diets with low inclusion, regardless of roughage source. Feed
efficiency tended to be different among treatments ( = 0.09), with cattle fed no
roughage having greater G:F than all treatments ( <= 0.06) except cattle fed the
low level of CSTK, which had a similar G:F ( = 0.48). Feed efficiency was not
affected by source of roughage ( = 0.23) or inclusion of roughage ( = 0.49). In
Exp. 2, 6 ruminally fistulated steers (347 kg BW [SD 25]) were used in a 6 * 6
Latin square design. Treatments were arranged as a 2 * 3 factorial with ALF or
CSTK included at zero, low, or standard levels similar to Exp. 1. Apparent total
tract digestibility (%) of DM, OM, and NDF decreased linearly ( <= 0.07) due to
increasing roughage inclusion. Average, maximum, and minimum ruminal pH increased
linearly ( <= 0.09) as roughage inclusion was increased. Based on the results of
this study, low levels of CSTK improved cattle performance relative to low
inclusions of ALF or CSIL. Diets with standard inclusions of ALF, CSIL, or CSTK
had similar performance. Roughage sources can be exchanged to provide equal NDF
in finishing diets containing 30% WDGS without negatively impacting finishing
cattle. Based on ADG, eliminating roughages when 30% WDGS was included in
finishing diets was not beneficial.
PMID- 26440337
TI - Effects of flaxseed encapsulation on biohydrogenation of polyunsaturated fatty
acids by ruminal microorganisms: feedlot performance, carcass quality, and tissue
fatty acid composition.
AB - The objective of this study was to evaluate the efficacy of protecting PUFA
within ground flaxseed against ruminal biohydrogenation by encapsulating them in
a matrix consisting of a 1:1 blend of ground flaxseed and dolomitic lime hydrate
(L-Flaxseed). Crossbreed heifers ( = 462, 346 +/- 19 kg) were blocked by weight
and randomly assigned to pens. Pens were assigned to 1 of 6 dietary treatments in
a randomized complete block design. Treatment 1 consisted of a combination of
54.6% steam-flaked corn (SFC), 30.0% wet corn gluten feed, 8.0% roughage, and
supplement (0% flaxseed). In treatments 2 and 3, a proportion of SFC was replaced
with 3 and 6% flaxseed, respectively; in treatments 4, 5, and 6, SFC was replaced
with 2, 4, or 6% L-Flaxseed, respectively. Cattle were fed for 140 or 168 d and
then harvested in a commercial abattoir where carcass data were collected.
Approximately 24 h after harvest, carcasses were evaluated for 12th-rib fat
thickness, KPH, LM area, marbling score, and USDA yield and quality grades.
Samples of LM were also obtained for determination of long-chain fatty acid
profiles. Cattle that were fed diets with 4 and 6% L-Flaxseed consumed less feed
than other treatments ( < 0.05), which adversely affected ADG. Compared with
cattle fed 0% flaxseed, cattle in these treatments had lower final BW (18 and 45
kg less for the 4 and 6% L-Flaxseed treatments, respectively), less ADG (0.16 and
0.48 kg/day less for the 4 and 6% L-Flaxseed treatments, respectively), and lower
carcass weights, dressing percentages, LM areas, backfat thicknesses, and
marbling scores ( < 0.05). The addition of flaxseed or 2% L-Flaxseed did not
affect performance or carcass traits ( > 0.05). Supplementation with flaxseed
increased ( < 0.05) the concentration of alpha-linolenic acid (ALA) in meat
(0.173, 0.482, 0.743 mg/g for 0, 3, and 6% flaxseed, respectively). Furthermore,
proportionate increases in the ALA content of muscle tissue were 47% greater when
flaxseed was encapsulated within the dolomitic lime hydrate matrix (0.288, 0.433,
0.592 mg/g for 2, 4, and 6% L-Flaxseed, respectively). Both products showed a
linear response in ALA concentration ( > 99%; increases for Flaxseed and L
Flaxseed of 0.095 and 0.140 mg of ALA/g of tissue for each percentage of flaxseed
added). This study indicates that a matrix consisting of dolomitic lime hydrate
is an effective barrier to ruminal biohydrogenation of PUFA; however, adverse
effects on DMI limit the amounts that can be fed.
PMID- 26440338
TI - Chemical composition, silage fermentation characteristics, and in vitro ruminal
fermentation parameters of potato-wheat straw silage treated with molasses and
lactic acid bacteria and corn silage.
AB - The aim of this study was to determine the effect of molasses and lactic acid
bacteria (LAB) on the chemical composition, silage fermentation characteristics,
and in vitro ruminal fermentation parameters of an ensiled potato-wheat straw
mixture in a completely randomized design with 4 replicates. Wheat straw was
harvested at full maturity and potato tuber when the leaves turned yellowish. The
potato-wheat straw (57:43 ratio, DM basis) mixture was treated with molasses,
LAB, or a combination. Lalsil Fresh LB (Lallemand, France; containing NCIMB
40788) or Lalsil MS01 (Lallemand, France; containing MA18/5U and MA126/4U) were
each applied at a rate of 3 * 10 cfu/g of fresh material. Treatments were mixed
potato-wheat straw silage (PWSS) without additive, PWSS inoculated with Lalsil
Fresh LB, PWSS inoculated with Lalsil MS01, PWSS + 5% molasses, PWSS inoculated
with Lalsil Fresh LB + 5% molasses, PWSS inoculated with Lalsil MS01 + 5%
molasses, and corn silage (CS). The compaction densities of PWSS treatments and
CS were approximately 850 and 980 kg wet matter/m, respectively. After anaerobic
storage for 90 d, chemical composition, silage fermentation characteristics, in
vitro gas production (GP), estimated OM disappearance (OMD), ammonia-N, VFA,
microbial CP (MCP) production, and cellulolytic bacteria count were determined.
Compared to CS, PWSS had greater ( < 0.001) values of DM, ADL, water-soluble
carbohydrates, pH, and ammonia-N but lower ( < 0.05) values of CP, ash free-NDF
(NDFom), ash, nitrate, and lactic, acetic, propionic, and butyric acids
concentrations. When PWSS was treated with molasses, LAB, or both, the contents
of CP and lactic and acetic acids increased, whereas NDFom, ammonia-N, and
butyric acid decreased ( < 0.05). Based on in vitro ruminal experiments, PWSS had
greater ( < 0.05) values of GP, OMD, and MCP but lower ( < 0.05) VFA and acetic
acid compared to CS. With adding molasses alone or in combination with LAB
inoculants to PWSS, the values of GP, OMD, MCP, cellulolytic bacteria population,
VFA, and propionic acid increased ( < 0.05), whereas the acetic acid to propionic
acid ratio decreased ( < 0.05). Overall, ensiling potato with wheat straw at a
57:43 ratio DM basis was possible; nevertheless, the fermentation quality of PWSS
was lesser than that of CS. However, addition of molasses and molasses + LAB
improved fermentation quality of PWSS.
PMID- 26440339
TI - Effects of feeding a spray-dried multivalent polyclonal antibody preparation on
feedlot performance, feeding behavior, carcass characteristics, rumenitis, and
blood gas profile of Brangus and Nellore yearling bulls.
AB - The objective of this study was to evaluate the effects of replacing monensin
(MON) with a spray-dried multivalent polyclonal antibody preparation (PAP)
against several ruminal microorganisms on feedlot performance, carcass
characteristics, feeding behavior, blood gas profile, and the rumenitis incidence
of Brangus and Nellore yearling bulls. The study was designed as a completely
randomized design with a 2 * 2 factorial arrangement, replicated 6 times (4 bulls
per pen and a total of 24 pens), in which bulls ( = 48) of each biotype were fed
diets containing either MON fed at 300 mg/d or PAP fed at 3 g/d. No significant
feed additive main effects were observed for ADG ( = 0.27), G:F ( = 0.28), HCW (
= 0.99), or dressing percentage ( = 0.80). However, bulls receiving PAP had
greater DMI ( = 0.02) and larger ( = 0.02) final LM area as well as greater ( <
0.01) blood concentrations of bicarbonate and base excess in the extracellular
fluid than bulls receiving MON. Brangus bulls had greater ( < 0.01) ADG and DMI
expressed in kilograms, final BW, heavier HCW, and larger initial and final LM
area than Nellore bulls. However, Nellore bulls had greater daily DMI fluctuation
( < 0.01), expressed as a percentage, and greater incidence of rumenitis ( =
0.05) than Brangus bulls. In addition, Brangus bulls had greater ( < 0.01) DMI
per meal and also presented lower ( < 0.01) DM and NDF rumination rates when
compared with Nellore bulls. Significant interactions ( < 0.05) between biotype
and feed additive were observed for SFA, unsaturated fatty acids (UFA), MUFA, and
PUFA concentrations in adipose tissues. When Nellore bulls were fed PAP, fat had
greater ( < 0.05) SFA and PUFA contents but less ( < 0.01) UFA and MUFA than
Nellore bulls receiving MON. For Brangus bulls, MON led to greater ( < 0.05) SFA
and PUFA and less ( < 0.05) UFA and MUFA than Brangus bulls fed PAP. Feeding a
spray-dried PAP led to similar feedlot performance compared with that when
feeding MON. Spray-dried PAP might provide a new technology alternative to
ionophores.
PMID- 26440340
TI - Relationship of leptin concentrations with feed intake, growth, and efficiency in
finishing beef steers.
AB - The objective of this experiment was to determine the association of serum leptin
concentrations with production measures including DMI, ADG, and G:F as well as
carcass characteristics in genetically diverse finishing beef steers. Three
cohorts of steers ( = 473 total) were individually fed a finishing ration for 92,
64, and 84 d for cohort 1, 2, and 3, respectively. Serum was collected on d 42,
22, and 19 of the experiment for cohort 1, 2, and 3, respectively. Leptin
concentrations were positively correlated to DMI ( = 0.21, < 0.01) but negatively
correlated to grams DMI per kilogram initial BW ( = -0.21, < 0.01). Leptin
concentrations were also negatively correlated to ADG and G:F ( < 0.01). Leptin
concentrations were positively correlated to 12th-rib fat thickness, yield grade,
and marbling score ( < 0.01) and negatively correlated to LM area ( < 0.01).
Using a mixed model analysis (SAS 9.3; SAS Inst. Inc., Cary, NC) to account for
breed effects, leptin concentrations were positively associated with DMI ( =
0.01) and accounted for 1.10% of the variance. However, if initial BW and yield
grade were included as covariates to account for body size and fatness, leptin
was negatively associated with DMI ( = 0.02) and accounted for 0.54% of the
variance. Regardless of covariates included in the model, leptin was negatively
associated with ADG ( < 0.01) and G:F ( < 0.01) and accounted for 2.62 and 7.87%
of the variance for ADG and G:F, respectively. Leptin concentrations were also
positively associated with 12th-rib fat thickness, yield grade, and marbling
score ( < 0.01) and accounted for 14.74, 12.74, and 6.99% of the variance for
12th-rib fat, yield grade, and marbling score, respectively. Leptin
concentrations could be a useful physiological marker for growth and feed
efficiency of finishing beef cattle. Genetic influences on the biology of leptin
also need to be considered when using leptin as physiological marker for
production measures.
PMID- 26440341
TI - Effects of plant species, stage of maturity, and level of formic acid addition on
lipolysis, lipid content, and fatty acid composition during ensiling.
AB - Forage type and management influences the nutritional quality and fatty acid
composition of ruminant milk. Replacing grass silage with red clover (RC; L.)
silage increases milk fat 18:3-3 concentration. Red clover has a higher
polyphenol oxidase (PPO) activity compared with grasses, which has been suggested
to decrease lipolysis and . The present study characterized the abundance and
fatty acid composition of esterified lipid and NEFA before and after ensiling of
grass and RC to investigate the influence of forage species, growth stage, and
extent of fermentation on lipolysis. A randomized block design with a 2 * 3 * 4
factorial arrangement of treatments was used. Treatments comprised RC or a
mixture of timothy ( L.) and meadow fescue ( Huds.) harvested at 3 growth stages
and treated with 4 levels of formic acid (0, 2, 4, and 6 L/t). Lipid in silages
treated with 0 or 6 L/t formic acid were extracted and separated into 4 fractions
by TLC. Total PPO activity in fresh herbage and the content of soluble bound
phenols in all silages were determined. Concentrations of 18:3-3 and total fatty
acids (TFA) were higher ( < 0.001) for RC than for grass. For both forage
species, 18:3-3 and TFA content decreased linearly ( < 0.001) with advancing
growth stage, with the highest abundance at the vegetative stage. Most of lipid
in fresh RC and grass herbage (97%) was esterified, whereas NEFA accounted for
71% of TFA in both silages. Ensiling resulted in marginal increases in TFA
content and the amounts of individual fatty acids compared with fresh herbages.
Herbage total PPO activity was higher ( < 0.001) for RC than grass (11 vs. 0.11
MUkatal/g leaf fresh weight). Net lipolysis during ensiling was extensive for
both forage species (660 to 759 g/kg fatty acid for grass and 563 to 737 g/kg
fatty acid for RC). Formic acid application (0 vs. 6 L/t) resulted in a marked
decrease ( = 0.026) in net lipolysis during the ensiling of RC, whereas the
opposite was true ( = 0.026) for grass. In conclusion, results suggest that
formic acid addition during the ensilage of RC decreases lipolysis . For both
plant species, total PPO activity was not associated with the extent of lipolysis
. However, bound phenols formed via PPO activity appear to have a role in
protecting lipid and protein against degradation in grass and lowering
proteolysis of RC during ensiling.
PMID- 26440343
TI - Differential impact of birth weight and early growth on neonatal mortality in
puppies.
AB - Breeding kennels face a high rate of neonatal mortality, on which the impact of
nutrition remains to be determined. This study was designed to evaluate the
impact of birth weight (reflecting intrauterine growth) and early growth rate
(reflecting colostrum intake) on risk of neonatal mortality in puppies and to
determine the critical thresholds of both parameters. Puppies from various breeds
were weighed at birth ( = 514) and at 2 d of age, and the growth rate over that
period (early growth rate) was calculated for all survivors ( = 477). Linear
mixed models evaluated the effect of birth weight on mortality between birth and
2 d of age and the effect of both birth weight and early growth rate on mortality
between 2 and 21 d of age. Birth weight was influenced by litter size ( = 0.003),
with more low-birth-weight puppies (the lightest 25% within a breed size) in
large litters compared with smaller litters. Mortality over the first 2 d after
birth was associated with birth weight ( < 0.001), with 81.1% of dying puppies
characterized by a low birth weight. Mortality between 2 and 21 d of age was not
related to birth weight but was found to be associated with early growth rate ( <
0.001), with higher risk of death in puppies with growth rate at or below -4%
after the first 2 d of life. This study demonstrates the differential effect of
intrauterine nutrition impacting mortality during the first 2 d of life and that
of colostrum intake impacting mortality until 21 d of life. Birth weight and
early growth rate thresholds provided in this study allow identification of
puppies at risk, whereby provision can be made for adequate nursing to increase
their chances to survive.
PMID- 26440342
TI - Effects of porcine reproductive and respiratory syndrome virus on pig growth,
diet utilization efficiency, and gas release from stored manure.
AB - The objectives of this study were to examine the effects of porcine reproductive
and respiratory syndrome virus (PRRSV) infection and vaccination on pig growth,
dietary nutrient efficiency of utilization, manure output, and emissions of CO,
CH, HS, NO, and NH gases from stored manure. Forty-eight pigs, aged 21 d at the
start of the study, were subjected to 1 of 4 treatment combinations arranged in a
2 * 2 factorial design with main factors of PRRSV vaccination and PRRSV
infection. Body weight, ADFI, manure output, and nutrient efficiency of
utilization were assessed and gas emissions from stored manure were determined
daily from 50 to 78 d of age and for 24 d after completion of the animal phase.
Infection with PRRSV markedly reduced final BW, ADG, and ADFI ( < 0.01) and
reduced efficiencies of ADF and ether extract utilization ( = 0.05 and = 0.02,
respectively) regardless of vaccination status. No significant treatment effects
were found on manure output, manure pH, efficiencies of lignin utilization, and N
retention. Infecting pigs with PRRSV increased daily manure CO emission per pig (
= 0.01). There was an interaction between immunization and infection for NO per
pig with manure from uninfected, vaccinated pigs producing as much as the manure
from infected, vaccinated pigs whereas there was a difference by PRRSV infection
state for nonvaccinated pigs. There were also interactions between treatments for
HS and NO emissions per kilogram of manure volatile solids excreted ( = 0.01 and
= 0.0001, respectively) with the same pattern as for NO per pig; that is, the
vaccinated pigs had similar rates of emission regardless of infection state. Pigs
infected with PRRSV increased NO nitrogen per kilogram of total N excreted
compared with noninfected groups ( = 0.03). Collectively, these results indicated
that PRRSV infection caused decreased growth rates and nutrient utilization
efficiency and increased gas emissions from stored manure.
PMID- 26440344
TI - Effects of vaccination against respiratory pathogens on feed intake, metabolic,
and inflammatory responses in beef heifers.
AB - The objective of this study was to evaluate intake, metabolic, inflammatory, and
acute-phase responses in beef heifers vaccinated against pathogens that cause
bovine respiratory disease (BRD). Eighteen weaned Angus heifers (initial BW 257
+/- 3 kg; initial age 245 +/- 2 d) were ranked by BW and allocated to 2 groups,
which were assigned to 2 experiments of 7 d and the following treatments on d 1
of each experiment: 1) revaccinated against infectious bovine rhinotracheitis
virus, parainfluenza-3 virus, bovine respiratory syncytial virus, bovine viral
diarrhea Types 1 and 2 viruses, and (VAC; 2 mL [s.c.]) and 2) receiving a 2-mL
s.c. injection of 0.9% sterile saline (CON). The group receiving VAC in Exp. 1
was assigned to CON in Exp. 2 and vice versa. Heifers were weaned 21 d before
Exp. 1, when they all received the first dose of the aforementioned vaccine.
Heifers were maintained in individual pens and offered free-choice mixed alfalfa
grass hay and 3.5 kg/d (DM basis) of a corn-based supplement throughout the
study. During Exp. 1, hay and concentrate intake were evaluated daily. During
Exp. 2, blood samples were collected before (-2 and 0 h) and at 2, 4, 6, 8, 12,
16, 24, 36, 48, 60, 72, 96, 120, 144, and 168 h after treatment administration.
In Exp. 1, treatment * day interactions were detected ( < 0.01) for forage intake
and total DMI; these parameters were reduced ( <= 0.05) in VAC heifers compared
with CON heifers on d 1 and 2 by an average of 1.7 and 0.8 kg (DM basis),
respectively. In Exp. 2, mean serum tumor necrosis factor alpha (TNFalpha)
concentration was greater ( = 0.05) in VAC heifers compared with CON heifers and
treatment * hour interactions were detected for all plasma variables ( <= 0.02),
whereas a similar tendency was detected ( = 0.09) for blood alpha mRNA
expression. Haptoglobin concentrations were greater ( <= 0.05) in VAC heifers
compared with CON heifers from 16 to 120 h. Blood alpha mRNA expression was
greater ( = 0.05) in VAC heifers compared with CON heifers at 12 h. Cortisol
concentrations were greater ( <= 0.05) in VAC heifers compared with CON heifers
from 2 to 16 h. Insulin concentration was greater ( = 0.02) in VAC heifers
compared with CON heifers at 2 h. Leptin concentrations were greater ( <= 0.05)
in VAC heifers compared with CON heifers from 6 to 16 h. In conclusion,
vaccinating beef heifers against BRD pathogens decreased forage intake and total
DMI during the 2 d following vaccination in Exp. 1, which can be associated with
transient metabolic, inflammatory, and acute-phase responses elicited by
vaccination in Exp. 2.
PMID- 26440345
TI - The association between immunoglobulin G in sow colostrum and piglet plasma.
AB - Colostrum provides newborn piglets with energy and passive immunity and is
essential for survival of the piglets. The plasma concentration of immunoglobulin
G (IgG) in piglets is dependent on several factors, most importantly the
concentration of IgG in sow colostrum (colostrum IgG). The main aims of this
study were to investigate the variation in concentration of colostrum IgG between
herds and the individual sows within herd and to investigate factors associated
with plasma IgG concentrations in piglets (piglet IgG). From 4 herds (A to D),
876 piglets from 62 sows were included in the study. Colostrum was sampled from
sows immediately after expulsion of the first piglet and before the first
suckling (t1), midway through farrowing (just after the sixth piglet was born;
t2), and after the last piglet was born (t3). At d 1, 0.5 mL blood from piglets
was collected in tubes containing EDTA, and IgG concentrations were analyzed.
Mean colostrum IgG concentration across all herds was 53.9 g/L. Herd A had mean
colostrum IgG of 38.3 g/L, whereas the other 3 herds (B,C, and D) had mean
colostrum IgG of 47.4, 60.4, and 67.8 g/L, respectively. Colostrum IgG at t1, t2,
and t3 across all herds was 56.2, 53.7, and 42.5 g/L, respectively. Mean
concentration of piglet IgG across all samplings was 21.7 g/L. Multilevel linear
regression analysis was performed with piglet IgG (g/L) as outcome. In this
model, the herd effect accounted for 9% of the total variance and 34% of the
variance resided at sow level. Piglet IgG was associated with herd, birth order
(), body mass index (BMI) > 17 (kg/m), and colostrum IgG at t1 (g/L) with an
overall -value < 0.01. Herd D had the highest predicted mean level of piglet IgG.
The main model predicted that piglet IgG decreased linearly by 0.4 g/L with each
piglet born ( < 0.01). The model also predicted an increase by 0.1 g/L for each
gram per liter extra colostrum IgG in colostrum ( = 0.03). Piglets with a BMI
above 17 kg/m had a greater piglet IgG (+4.5 g/L) than those with a BMI at 17
kg/m or below ( < 0.01). Concentrations of colostrum IgG varied largely between
herds and between sows. The largest variation of piglet IgG was mainly on the
piglet level, supporting the complex nature of IgG production and uptake.
However, the strong association between colostrum IgG and piglet IgG shows that
increased IgG level in colostrum will improve the levels of IgG in piglets and
potentially increase survival of the piglets.
PMID- 26440346
TI - In vivo prediction of goat kids body composition from the deuterium oxide
dilution space determined by isotope-ratio mass spectrometry.
AB - Deuterium oxide dilution space (DOS) determination is one of the most accurate
methods for in vivo estimation of ruminant body composition. However, the time
consuming vacuum sublimation of blood preceding infrared spectroscopy analysis,
which is traditionally used to determine deuterium oxide (DO) concentration,
limits its current use. The use of isotope-ratio mass spectrometry (IRMS) to
determine the deuterium enrichment and thus quantify DO in plasma could
counteract this limitation by reducing the sample preparation for plasma
deproteinisation through centrifugal filters. The aim of this study was to
validate the DOS technique using IRMS in growing goat kids to establish in vivo
prediction equations of body composition. Seventeen weaned male Alpine goat kids
(8.6 wk old) received a hay-based diet supplemented with 2 types of concentrates
providing medium ( = 9) or high ( = 8) energy levels. Kids were slaughtered at
14.0 ( = 1, medium-energy diet), 17.2 ( = 4, medium-energy diet, and = 4, high
energy diet), or 21.2 wk of age ( = 4, medium-energy diet, and = 4, high-energy
diet). Two days before slaughter, DOS was determined after an intravenous
injection of 0.2 g DO/kg body mass (BM) and the resulting study of DO dilution
kinetics from 4 plasma samples (+5, +7, +29, and +31 h after injection). The
deuterium enrichment was analyzed by IRMS. After slaughter, the gut contents were
discarded, the empty body (EB) was minced, and EB water, lipid, protein, ash, and
energy contents were measured by chemical analyses. Prediction equations for body
components measured postmortem were computed from in vivo BM and DOS. The lack of
postmortem variation of fat-free EB composition was confirmed (mean of 75.3% [SD
0.6] of water), and the proportion of lipids in the EB tended ( = 0.06) to be
greater for the high-energy diet (13.1%) than for the medium-energy diet (11.1%).
There was a close negative relationship (residual CV [rCV] = 3.9%, = 0.957)
between EB water and lipid content, whereas DOS was closely related to total body
water (rCV = 2.9%, = 0.944) but DOS overestimated it by 5.8%. Adding DOS to BM
improved the in vivo predictions of EB lipid and energy content (rCV = 13.1% and
rCV = 7.9%, respectively) but not those of protein or ash. Accuracy of the
obtained prediction equations was similar to those reported in studies
determining DOS by infrared spectroscopy. Therefore, the use of IRMS to quantify
DOS provides a highly accurate measure of the in vivo body composition in goat
kids.
PMID- 26440347
TI - Increasing the metabolizable protein supply enhanced growth performance and led
to variable results on innate and humoral immune response of preconditioning beef
steers.
AB - We evaluated the effects of MP supply on growth performance before and after
preconditioning and measurements of innate and humoral immune response of beef
steers following vaccination. Angus steers ( = 36; BW = 231 +/- 21 kg; age = 184
+/- 18 d) were weaned on d -6, stratified by BW and age on d 0, and randomly
assigned to 1 of 18 drylot pens (2 steers/pen). Treatments were assigned to pens
(6 pens/treatment) and consisted of corn silage-based diets formulated to provide
85%, 100%, or 115% of the daily MP requirements of a beef steer gaining 1.1 kg/d
from d 0 to 42. Steers were vaccinated against infectious bovine rhinotracheitis
virus, bovine viral diarrhea (BVDV) types 1 and 2 viruses, and clostridium on d
14 and 28. Blood samples were collected on d 0, 14, 15, 17, 21, 28, 29, 30, 35,
and 42. Body weight did not differ ( >= 0.17) among treatments from d 0 to 28. On
d 42, 115% MP steers were heaviest, 100% MP steers were intermediate, and 85% MP
steers were lightest ( = 0.05; 297, 290, and 278 +/- 7 kg, respectively).
Overall, ADG and G:F did not differ ( >= 0.13) between 100% and 115% MP steers
and were least ( < 0.01) for 85% MP steers (1.2, 1.4, and 0.8 +/- 0.07 kg/d and
0.23, 0.24, and 0.19 +/- 0.008, respectively). Plasma haptoglobin (Hp)
concentrations did not differ among treatments ( >= 0.46), whereas plasma
ceruloplasmin (Cp) concentrations were greatest ( <= 0.04) for 85% MP steers,
intermediate for 100% MP steers, and least for 115% MP steers on d 30, 35, and
42. Plasma cortisol concentrations were greater ( <= 0.03) for 85% vs. 100% and
115% MP steers on d 14 and 28. Liver mRNA expression of Cp and Hp and muscle mRNA
expression of m-calpain, mammalian target of rapamycin, and ubiquitin did not
differ among treatments ( >= 0.17). Serum neutralization titers to BVDV-1b titers
were greater ( <= 0.02) for 115% vs. 85% and 100% MP steers on d 42 (5.8, 3.0,
and 3.7 +/- 0.60 log, respectively), whereas mean serum leukotoxin titers were
greater for 85% vs. 100% and 115% MP steers (3.1, 2.4, and 2.5 +/- 0.21 log,
respectively). Preconditioning MP supply did not affect ( >= 0.26) ubsequent
finishing growth performance and carcass characteristics. Thus, increasing MP
supply from 85% to 115% of daily requirement of preconditioning beef steers had
variable results on innate and humoral immune response and enhanced growth
performance during a 42-d preconditioning period without affecting carcass
characteristics at slaughter.
PMID- 26440348
TI - Effects of diet form and type on growth performance, carcass yield, and iodine
value of finishing pigs.
AB - Two experiments were conducted to determine the effects of pelleting, diet type
(fat and fiber level), and withdrawal of dietary fiber and fat before marketing
on growth performance, carcass yield, and carcass fat iodine value (IV) of
finishing pigs. Each experiment used 288 pigs (initially 49.6 and 48.5 kg BW,
respectively) with 6 dietary treatments arranged as 2 * 3 factorials. In Exp. 1,
main effects were diet form (meal vs. pellet) and diet regimen. Diet regimens
were 1) a low-fiber, low-fat (corn-soybean meal) diet from d 0 to 81, 2) a high
fiber, high-fat (30% dried distillers grains with solubles [DDGS] and 19% wheat
middlings [midds]) diet from d 0 to 64 followed by the low-fiber, low-fat diet
from d 64 to 81 (fiber and fat withdrawal), and 3) the high-fiber, high-fat diet
fed from d 0 to 81. Pigs fed pelleted diets had increased ( < 0.05) ADG and G:F
compared with those fed meal diets. Pigs fed pelleted diets had increased belly
fat IV (2.9 mg/g) compared with those fed meal diets, with a greater increase
when fed high-fiber, high-fat diets throughout the entire study (interaction, <
0.05). Pigs fed the low-fiber, low-fat diet throughout had increased ( < 0.001)
G:F compared with pigs fed the other 2 treatments. Pigs fed low-fiber, low-fat
diets throughout the study or pigs withdrawn from high-fiber, high-fat diets had
increased ( < 0.001) carcass yield compared with pigs fed high-fiber, high-fat
diets throughout. In Exp. 2, treatment main effects were diet form (meal vs.
pellet) and diet type (corn-soybean meal-based control, the control with 30% DDGS
and 19% midds, or the control diet with 3% corn oil). The diet containing corn
oil was calculated to produce carcass fat IV similar to diets containing DDGS and
midds. Overall, pigs fed pelleted diets had increased ( < 0.05) ADG, G:F, and
belly fat IV (1.3 mg/g) compared with those fed meal diets. Pigs fed the diets
containing DDGS and midds had decreased ( < 0.05) ADG, carcass yield, and HCW
compared with pigs fed the control or corn oil diets and decreased ( < 0.001) G:F
compared with pigs fed added corn oil. Belly IV was greatest ( < 0.001) for pigs
fed diets with DDGS and midds and lowest for pigs fed the control diet, with pigs
fed the corn oil diets intermediate. In conclusion, pelleting diets improves pig
ADG (approximately 3%) and G:F (approximately 6%); however, a novel finding of
this study is that pelleting diets fed to finishing pigs also increases belly fat
IV.
PMID- 26440349
TI - Glutamine synthetase and alanine transaminase expression are decreased in livers
of aged vs. young beef cows and GS can be upregulated by 17beta-estradiol
implants.
AB - Aged beef cows (>= 8 yr of age) produce calves with lower birth and weaning
weights. In mammals, aging is associated with reduced hepatic expression of
glutamine synthetase (GS) and alanine transaminase (ALT), thus impaired hepatic
Gln-Glu cycle function. To determine if the relative protein content of GS, ALT,
aspartate transaminase (AST), glutamate transporters (EAAC1, GLT-1), and their
regulating protein (GTRAP3-18) differed in biopsied liver tissue of (a) aged vs.
young (3 to 4 yr old) nonlactating, nongestating Angus cows (Exp. 1 and 2) and
(b) aged mixed-breed cows with and without COMPUDOSE (17beta-estradiol) ear
implants (Exp. 3), Western blot analyses were performed. In Exp. 1, 12 young
(3.62 +/- 0.01 yr) and 13 aged (10.08 +/- 0.42 yr) cows grazed the same mixed
forage for 42 d (August-October). In Exp. 2, 12 young (3.36 +/- 0.01 yr) and 12
aged (10.38 +/- 0.47 yr) cows were individually fed (1.03% of BW) a corn-silage
based diet to maintain BW for 20 d. For both Exp. 1 and 2, the effect of cow age
was assessed by ANOVA using the MIXED procedure of SAS. Cow BW did not change (
>= 0.17). Hepatic ALT (78% and 61%) and GS (52% and 71%) protein content (Exp. 1
and 2, respectively) was decreased ( <= 0.01), whereas GTRAP3-18 (an inhibitor of
EAAC1 activity) increased ( <= 0.01; 170% and 136%) and AST, GLT-1, and EAAC1
contents did not differ ( >= 0.17) in aged vs. young cows. In Exp. 2, free
concentrations (nmol/g) of Glu, Ala, Gln, Arg, and Orn in liver homogenates were
determined. Aged cows tended to have less ( = 0.10) free Gln (15.0%) than young
cows, whereas other AA concentrations did not differ ( 0.26). In Exp. 3, 14 aged
(> 10 yr) cows were randomly allotted ( = 7) to sham or COMPUDOSE (25.7 mg of
17beta-estradiol) implant treatment (TRT), and had ad libitum access to alfalfa
hay for 28 d. Blood and liver biopsies were collected 14 and 28 d after implant
treatment. Treatment, time after implant (DAY), and TRT * DAY effects were
assessed by ANOVA using the MIXED procedure of SAS. Cow BW was not affected ( >=
0.96). Implant increased ( <= 0.02) total plasma estradiol by 220% (5.07 vs. 1.58
pg/mL) and GS protein by 300%, whereas the relative content of other proteins was
not altered ( >= 0.16). We conclude that hepatic expression of ALT and GS are
reduced in aged vs. young cows, and administration of 17beta-estradiol to aged
cows increases plasma estradiol and hepatic GS, but not that of other proteins
that support hepatic Glu metabolism.
PMID- 26440350
TI - Characterization of protected designation of origin Italian meat products
obtained from heavy pigs fed barley-based diets.
AB - A study was conducted to evaluate the quality and sensory properties of protected
designation of origin (PDO) Parma ham and Piacentina neck obtained from heavy
pigs (Italian Duroc * Italian Large White) fed barley-based diets. Four diets
were tested: 1) a corn-based diet (control), 2) the control diet with 80% of a
normal-amylose hulled barley variety (Cometa), 3) the control diet with 80% of a
normal-amylose hulless barley variety (Astartis), and 4) the control diet with
80% of a low-amylose hulless barley variety (Alamo). All the meat products were
analyzed for physicochemical and color parameters. The dry-cured hams and necks
were also evaluated for sensory properties. The data of physicochemical, color,
and sensory parameters were separately analyzed by multivariate factor analysis,
and interpretation of each extracted factor was based on specific original
variables loading on each one. The meat products obtained from pigs fed the
barley-based diets differed from those obtained from the control pigs on the PUFA
factors characterized by C18:2-6 and omega-3:omega-6 ratio. In particular, the
meat products obtained from pigs fed the barley-based diets had a lower content
of C18:2-6 and a higher omega-3:omega-6 ratio ( < 0.05) than the control. In
fresh hams, iodine number and SFA (C16:0 and C18:0) in addition to PUFA and omega
3:omega-6 ratio loaded on the PUFA/SFA factor. The fresh hams produced from pigs
fed the barley-based diets had subcutaneous fat (SC) with a lower iodine number
and a higher SFA level compared with those produced from the control pigs ( <
0.05). A sex effect was measured for PUFA/SFA and oleic acid factors. In
particular, the barrow SC had a lower SFA content, higher PUFA and C18:1-9
levels, and a higher iodine number ( < 0.05) than the gilt SC. There were no
appreciable differences in the color and sensory properties of meat products
obtained from pigs fed the different diets. The hams from barrows differed from
those obtained from gilts on the lean properties factor describing properties
related to aspect and odor of dry-cured hams. Indeed, the hams from barrows were
depreciated compared with the hams from gilts for minor intensity, brightness,
and uniformity of the lean, pinkish intermuscular fat and cured odor. In
conclusion, barley could be used as a replacement for corn in heavy pig diets for
the production of PDO Italian products without negative effects on the
physicochemical, color, or sensory characteristics of meat products.
PMID- 26440351
TI - Impact of divergent selection for ultimate pH of pectoralis major muscle on
biochemical, histological, and sensorial attributes of broiler meat.
AB - The impact of divergent selection based on the ultimate pH (pHu) of pectoralis
major (P. major) muscle on the chemical, biochemical, and histological profiles
of the muscle and sensorial quality of meat was investigated in broiler chickens.
The protein, lipid, DM, glycogen and lactate content, glycolytic potential,
proteolysis, lipid and protein oxidation index, muscle fiber cross-sectional
area, capillary density, and collagen surface were determined on the breast P.
major muscle of 6-wk-old broilers issued from the high-pHu (pHu+) and low-pHu
(pHu-) lines. Sensory attributes were also evaluated on the breast (roasted or
grilled) and thigh (roasted) meat of the 2 lines. Protein, lipid, and DM content
of P. major muscle were not affected by selection ( > 0.05). However, the P.
major muscle of the pHu+ line was characterized by lower residual glycogen (-16%;
<= 0.001) and lactate (-14%; <= 0.001) content and lower glycolytic potential (
14%; <= 0.001) compared with the pHu- line. Although the average cross-sectional
area of muscle fibers and surface occupied by collagen were similar ( > 0.05) in
both lines, fewer capillaries per fiber (-15%; <= 0.05) were observed in the pHu+
line. The pHu+ line was also characterized by lower lipid oxidation
(thiobarbituric acid reactive substance index: -23%; <= 0.05) but protein
oxidation and proteolysis index were not different ( > 0.05) between the 2 lines.
At the sensory level, selection on breast muscle pHu mainly affected the texture
of grilled and roast breast meat, which was judged significantly more tender ( <=
0.001) in the pHu+ line, and the acid taste, which was less pronounced in the
roasted breast meat of the pHu+ line ( <= 0.002). This study highlighted that
selection based on pHu does not affect the chemical composition and structure of
breast meat. However, by modifying muscle blood supply and glycogen turnover, it
affects meat acidity and oxidant status, both of which are likely to contribute
to the large differences in texture observed between the 2 lines.
PMID- 26440352
TI - Effects of supplemental lysine and methionine with zilpaterol hydrochloride on
feedlot performance, carcass merit, and skeletal muscle fiber characteristics in
finishing feedlot cattle.
AB - Feeding zilpaterol hydrochloride (ZH) with ruminally protected AA was evaluated
in a small-pen feeding trial. Crossbred steers ( = 180; initial BW = 366 kg) were
blocked by weight and then randomly assigned to treatments (45 pens; 9
pens/treatment). Treatment groups consisted of no ZH and no AA (Cont-), ZH and no
AA (Cont+), ZH and a ruminally protected lysine supplement (Lys), ZH and a
ruminally protected methionine supplement (Met), and ZH and ruminally protected
lysine and methionine (Lys+Met). Zilpaterol hydrochloride (8.3 mg/kg DM) was fed
for the last 20 d of the finishing period with a 3-d withdrawal period. Lysine
and Met were top dressed daily for the 134-d feeding trial to provide 12 or 4
g.hd.d, respectively, to the small intestine. Carcass characteristics,
striploins, and prerigor muscle samples were collected following harvest at a
commercial facility. Steaks from each steer were aged for 7, 14, 21, and 28 d,
and Warner-Bratzler shear force (WBSF) was determined as an indicator of
tenderness. Prerigor muscle samples were used for immunohistological analysis.
Cattle treated with Met and Lys+Met had increased final BW ( < 0.3) and ADG ( <
0.05) compared to Cont- and Cont+. Supplementation of Lys, Met, and Lys+Met
improved G:F ( < 0.05) compared to Cont- during the ZH feeding period (d 111 to
134) as well as the entire feeding period ( < 0.05). Zilpaterol hydrochloride
increased carcass ADG ( < 0.05) when compared to non-ZH-fed steers. Methionine
and Lys+Met treatments had heavier HCW ( < 0.02) than that of Cont-. Yield grade
was decreased ( < 0.04) for Cont+ steers compared to steers treated with Lys,
Lys+Met, and Cont-. Tenderness was reduced ( < 0.05) with ZH regardless of AA
supplementation. Lysine, Met, Lys+Met, and Cont+ had less tender steaks ( < 0.05)
throughout all aging groups compared to Cont-. Steaks from Lys-treated steers
were less tender ( < 0.05) than those of Cont+ during the 7- and 14-d aging
periods. Nuclei density was the greatest with Cont- cattle compared to all other
treatments suggesting a dilution effect of the nuclei in the larger muscle fibers
with ZH feeding. Supplementation of Met in conjunction with ZH feeding increased
ADG and HCW although this may lead to decreased tenderness even after aging for
28 d. These findings indicated that steers fed ZH may require additional AA
absorbed from the small intestine to maximize performance.
PMID- 26440353
TI - Carcass traits and cutting yields of entire and immunocastrated pigs fed
increasing protein levels with and without ractopamine hydrochloride
supplementation.
AB - The objective of this study was to determine the effects of increasing balanced
protein, with and without ractopamine hydrochloride (RAC), in the finisher diets
of immunocastrates on their carcass cutting yields and respective muscle, fat,
and bone proportions. Carcass traits and yields of 120 individually housed entire
male pigs and immunocastrates were evaluated following a 2 * 2 * 3 factorial
design. Vaccination occurred at 16 and 20 wk of age and slaughtering at 24 wk. Up
until 20 wk of age, all pigs received a commercial grower diet. Low-, medium-,
and high-protein (7.50, 9.79, and 12.07 g standardized ileal digestible [SID]
lysine/kg, respectively) diets were then fed for the last 28 d with RAC
supplemented at 0 or 10 mg/kg. Immunocastration and RAC supplementation increased
( = 0.003 and = 0.017, respectively) the live weight at slaughter. The
interaction between sex and protein ( = 0.039) for caliper backfat depths showed
greater backfat depths in immunocastrates fed medium protein whereas RAC
decreased ( = 0.027) the caliper backfat depth. Feeding RAC increased the
trotters ( = 0.040), tenderloins (fillets; < 0.001), shoulder ( = 0.002),
hindquarter ( = 0.026), loin ( = 0.028), and belly ( = 0.044) percentages. The
shoulder ( < 0.001), hindquarter ( < 0.001), and loin ( = 0.005) muscle
percentages were increased and the hindquarter fat percentages were decreased ( =
0.032) with RAC supplementation. Immunocastration increased the belly cut ( =
0.006), loin fat ( < 0.001), and belly fat ( < 0.001) percentages. Therefore,
carcass cutting and lean yields can be improved by RAC supplementation while
decreasing the backfat depth, and the increase in backfat due to immunocastration
could be avoided with the correct dietary protein level.
PMID- 26440354
TI - Assessment of nonpenetrating captive bolt stunning followed by electrical
induction of cardiac arrest in veal calves.
AB - The purpose of this study was to evaluate the impact of nonpenetrating captive
bolt stunning followed by electrical induction of cardiac arrest on veal calf
welfare, veal quality, and blood yield. Ninety calves from the same farm were
randomly assigned to 1 of 2 treatment groups in a balanced unpaired comparison
design. The first treatment group (the "head-only" method-application of the
pneumatic nonpenetrating stun to the frontal plate of the skull at the
intersection of 2 imaginary lines extending from the lateral canthus to the
opposite poll [CONTROL]) was stunned with a nonpenetrating captive bolt gun ( =
45). The second group ( = 45) was stunned with a nonpenetrating captive bolt gun
followed by secondary electrical induction of cardiac arrest (the "head/heart"
method-initial application of the pneumatic nonpenetrating captive bolt stun
followed by 1 s application of an electrical stun to the ventral region of the
ribcage directly caudal to the junction of the humerus and scapula while the
stunned calf was in lateral recumbence [HEAD/HEART]). Stunning efficacy was the
indicator of animal welfare used in this study. All calves were instantly
rendered insensible by the initial stun and did not display common indicators of
return to consciousness. For meat quality evaluation, all samples were collected
from the 12th rib region of the longissimus thoracis. Meat samples were evaluated
for color, drip loss, ultimate pH, cook loss, and Warner-Bratzler shear force.
The L* values (measure of meat color lightness) were darker ( < 0.05) in the
HEAD/HEART group (45.08 +/- 0.72) than the CONTROL group (47.10 +/- 0.72). There
were no differences ( > 0.05) observed in a* (redness) and b* (yellowness) values
between treatments. No differences ( > 0.05) were observed in drip loss, ultimate
pH, cook loss, and Warner-Bratzler shear force. The blood yield from the CONTROL
group (7,217.9 +/- 143.5 g) was greater ( < 0.05) than that from the HEAD/HEART
group (6,656.4 +/- 143.5 g). Overall, the data indicated no difference between
the CONTROL and HEAD/HEART groups with regard to animal welfare because the
initial stun was effective in all calves. However, longissimus thoracis L* and
blood yield were negatively impacted by the HEAD/HEART method. The data in this
study suggest that secondary induction of cardiac arrest is not necessary with
effective nonpenetrating captive bolt stunning in veal calves.
PMID- 26440355
TI - A Nordic survey of management practices and owners' attitudes towards keeping
horses in groups.
AB - Keeping horses in groups is widely recommended but limited information is
available about how this is implemented in practice. The aim of this survey was
to describe how horses are kept in the Nordic countries in relation to sex, age,
breed, and equestrian discipline and to assess owners' attitudes toward keeping
horses in groups. Horse owners in Denmark, Finland, Norway, and Sweden were
approached using a web-based questionnaire, which was translated into 4 languages
and distributed online via equestrian forums, organizations, and social media.
The number of respondents was 3,229, taking care of 17,248 horses. Only 8% of
horses were never kept in groups, 47% were permanently grouped for 24 h/d, and
45% were stabled singly but grouped during turnout. Yearlings were most often
permanently kept in groups (75%), mares and geldings more commonly during parts
of the day (50 and 51%, respectively), and stallions were often kept alone (38%).
Icelandic horses were more likely to be permanently kept in groups (36%) than
warmbloods (16%) and ponies (15%). Twice as many competition horses (51%) were
never grouped compared with horses used for breeding (20%) or leisure purposes
(15%). The majority of respondents (86%) strongly agreed that group housing
benefits horse welfare and that it is important for horses to have the company of
conspecifics (92%). Nevertheless, not all horses were kept in groups, showing
that attitudes toward group housing may not necessarily reflect current
management. The risk of injury was a concern of many respondents (45%), as was
introducing unfamiliar horses into already established groups (40%) and
challenges in relation to feeding in groups (44%). Safety of people (23%) and
difficulties handling group-kept horses (19%) were regarded as less problematic.
Results suggest that the majority of horses have the possibility to freely
interact with other horses, either as fulltime members of a group during 24 h/d
or during turnout. Future research should address the extent to which being a
part-time member of a group affects horse welfare. For permanent group housing to
become more widespread, such as it is the case for most farm animals, future
research could focus on solving some of the reoccurring problems perceived with
keeping horses in groups. The dissemination of evidence-based information on all
aspects around keeping horses in groups can ultimately stimulate further positive
changes in the management of group-kept horses.
PMID- 26440356
TI - Technical note: A method for assigning animals to treatment groups with unequal
count per group that equalizes mean animal weight among groups.
AB - Pastures available for grazing studies may be of unequal size and may have
heterogeneous carrying capacity necessitating the assignment of unequal numbers
of animals per pasture. To reduce experimental error, it is often desirable that
the initial mean BW be similar among experimental units. The objective of this
note is to present and illustrate the use of a method for assignment of animals
to experimental units of different sizes such that the initial mean weight of
animals in each unit is approximately the same as the overall mean. Two
alternative models were developed and solved to assign each of 231 weaned steers
() to 1 of 12 pastures with carrying capacity ranging from 5 to 26 animals per
pasture. A solution to Model 1 was obtained in which the mean weights among
pastures were approximately the same but the variances among pastures were
heteroskedastic, meaning that weight variances across pens were different (-value
< 0.05). An alternative model was developed (Model 2) and used to derive
assignments with nearly equal mean weights and homoskedastic variances among
pastures.
PMID- 26440357
TI - Erratum.
PMID- 26440358
TI - Headache attributed to masticatory myofascial pain: impact on facial pain and
pressure pain threshold.
AB - There is no clear evidence on how a headache attributed to temporomandibular
disorder (TMD) can hinder the improvement of facial pain and masticatory muscle
pain. The aim of this study was to measure the impact of a TMD-attributed
headache on masticatory myofascial (MMF) pain management. The sample was
comprised of adults with MMF pain measured according to the revised research
diagnostic criteria for temporomandibular disorders (RDC/TMD) and additionally
diagnosed with (Group 1, n = 17) or without (Group 2, n = 20) a TMD-attributed
headache. Both groups received instructions on how to implement behavioural
changes and use a stabilisation appliance for 5 months. The reported facial pain
intensity (visual analogue scale--VAS) and pressure pain threshold (PPT--kgf cm(
2)) of the anterior temporalis, masseter and right forearm were measured at three
assessment time points. Two-way anova was applied to the data, considering a 5%
significance level. All groups had a reduction in their reported facial pain
intensity (P < 0.001). Mean and standard deviation (SD) PPT values, from 1.33
(0.54) to 1.96 (1.06) kgf cm(-2) for the anterior temporalis in Group 1 (P =
0.016), and from 1.27 (0.35) to 1.72 (0.60) kgf cm(-2) for the masseter in Group
2 (P = 0.013), had significant improvement considering baseline versus the 5th
month assessment. However, no differences between the groups were found (P >
0.100). A TMD-attributed headache in patients with MMF pain does not negatively
impact pain management, but does change the pattern for muscle pain improvement.
PMID- 26440359
TI - Trafficking of Gold Nanoparticles Coated with the 8D3 Anti-Transferrin Receptor
Antibody at the Mouse Blood-Brain Barrier.
AB - Receptor-mediated transcytosis has been widely studied as a possible strategy to
transport neurotherapeutics across the blood-brain barrier (BBB). Monoclonal
antibodies directed against the transferrin receptor (TfR) have been proposed as
potential carrier candidates. A better understanding of the mechanisms involved
in their cellular uptake and intracellular trafficking is required and could
critically contribute to the improvement of delivery methods. Accordingly, we
studied here the trafficking of gold nanoparticles (AuNPs) coated with the 8D3
anti-transferrin receptor antibody at the mouse BBB. 8D3-AuNPs were intravenously
administered to mice and allowed to recirculate for a range of times, from 10 min
to 24 h, before brain extraction and analysis by transmission electron microscope
techniques. Our results indicated a TfR-mediated and clathrin-dependent
internalization process by which 8D3-AuNPs internalize individually in vesicles.
These vesicles then follow at least two different routes. On one hand, most
vesicles enter intracellular processes of vesicular fusion and rearrangement in
which the AuNPs end up accumulating in late endosomes, multivesicular bodies or
lysosomes, which present a high AuNP content. On the other hand, a small
percentage of the vesicles follow a different route in which they fuse with the
abluminal membrane and open to the basal membrane. In these cases, the 8D3-AuNPs
remain attached to the abluminal membrane, which suggests an endosomal escape,
but not dissociation from TfR. Altogether, although receptor-mediated transport
continues to be one of the most promising strategies to overcome the BBB,
different optimization approaches need to be developed for efficient drug
delivery.
PMID- 26440360
TI - Stable Self-Assembly of Bovine alpha-Lactalbumin Exhibits Target-Specific
Antiproliferative Activity in Multiple Cancer Cells.
AB - Self-assembly of a protein is a natural phenomenon; however, the process can be
performed under a suitable condition in vitro. Since proteins are nontoxic,
biodegradable, and biocompatible in nature, they are used in various industrial
applications such as biocatalyst, therapeutic agent, and drug carriers. Moreover,
their flexible structural state and specific activity are being used as sensors
and immensely attract many new applications. However, the inherent potential of
protein self-assembly for various applications is yet to be explored in detail.
In this study, spherical self-assembly of bovine alpha-lactalbumin (nsBLA) was
synthesized using an optimized ethanol-mediated desolvation process with an
average diameter of approximately 300 nm. The self-assembly was found to be
highly stable against thermal, pH, and proteases stress. When nsBLA was
administered in various cancer cells, it demonstrated high cytotoxicity in three
different cancer cells via reactive oxygen species (ROS) generation, whereas it
exhibited negligible toxicity in normal human and murine cells. When nsBLA was
conjugated with folic acid, it improved the cytotoxicity and perhaps mediated
through enhanced cellular uptake in cancer cells through binding with folate
receptors. Further, experimental results confirmed that the cancer cell death
induced by nsBLA was not caused by apoptosis but a necrotic-like death mechanism.
When compared with a well-known protein-based anticancer agent BAMLET (bovine
alpha-lactalbumin made lethal against tumor cell), the self-assembled BLA clearly
exhibited higher cytotoxicity to cancer cells than BAMLET. While BAMLET exhibits
poor biocompatibility, our nsBLA demonstrated excellent biocompatibility to
normal cells. Therefore, in this study, we prepared self-assembled alpha
lactalbumin that exhibits strong inherent antiproliferative potential in multiple
cancer cells which can be used for efficient therapeutic approach in cancer.
PMID- 26440361
TI - Serum leptin concentration in women of reproductive age with euthyroid autoimmune
thyroiditis.
AB - INTRODUCTION: Autoimmune thyroid disease (AITD) with elevated anti-thyroid
peroxidase antibody (aTPO) levels appears in 12-25% of all women, apart from
thyroid dysfunction. High titers of aTPO are more common in women with polycystic
ovary syndrome and endometriosis. Elevated aTPO has been associated with
infertility and poorer quality of life among euthyroid women, and may be related
to other factors. OBJECTIVES: The aim of the study was to measure differences in
serum leptin concentration between AITD+ and AITD- patients. Setting, patients
and main outcome measures: The sample was comprised of 74 women who were
hospitalized in the Department of Gynecological Endocrinology, Medical University
of Warsaw. Data collected included age, body mass index (BMI), and serum aTPO,
serum thyroid stimulating hormone (TSH), serum fT4, serum follitropin (FSH),
serum estradiol and serum leptin. AITD positive status was defined as serum aTPO
greater than 5.6 mIU/ml. RESULTS: Serum leptin concentrations were significantly
higher in AITD+ patients compared to AITD- patients (17.13 ng/ml [SD 7.66] versus
12.78 ng/ml [SD 7.28]; p < 0.05). No differences by AITD status were found in
age, BMI, TSH, FSH, estradiol and fT4. CONCLUSIONS: Serum leptin concentrations
were higher in patients with AITD than in patients without AITD.
PMID- 26440362
TI - Polyoxomolybdate-Calix[4]arene Hybrid: A Catalyst for Sulfoxidation Reactions
with Hydrogen Peroxide.
AB - An easily accessible polyoxomolybdate-calix[4]arene hybrid 1 has been synthesized
and applied as a heterogeneous catalyst in the sulfoxidation of thioethers to
sulfoxides and to sulfones under strictly stoichiometric amounts of 30% H2O2 in
CH3CN as the solvent. This study represents the first promising example of
successful employment of calixarenes-polyoxometalate (POM) hybrid materials in
the area of catalytic oxidations.
PMID- 26440363
TI - DNA double-strand breaks induced intractable glomerular fibrosis in renal
allografts.
AB - BACKGROUNDS: The relationship between DNA damage and glomerular fibrosis in renal
allografts remains unclear. METHODS: We examined renal allograft specimens from
35 patients in which DNA double-strand breaks (DSBs) and glomerular fibrosis were
detected by phospho-histone H2A.X (gamma-H2AX) expression and collagen (COL)
types III, IV, and VI accumulation. We also examined the in vitro relationship
between DNA damage and COL accumulation by mitomycin C (MMc)-induced DNA damage
in human glomerular endothelial cells (HRGEc). RESULTS: The gamma-H2AX and COL
type VI, which mainly accumulated in the subendothelial and mesangial regions,
were positively correlated with the duration of the post-renal transplant (RT)
period. In multiple regression analysis, the duration of the post-RT period and
cg in the Banff '07 classification were identified as a significant predictor of
COL type VI accumulation and gamma-H2AX expression in the glomerular capillaries.
In addition, the gamma-H2AX-positive area was also identified as a predictor of
glomerular accumulation of COL type VI. COL type VI was detected in the cytoplasm
of the HRGEc, which was secreted into the supernatant after MMc stimulation with
gamma-H2AX expression. The number of gamma-H2AX (-)/COL type VI (+) cells was
inversely associated with the number of gamma-H2AX (+)/COL type VI (-) cells
during 24-h MMc treatment. CONCLUSIONS: Our findings suggest that the long-term
RT induces DSBs and HRGEc-secreted COL type VI accumulation in the glomerular
capillaries, which might progress to intractable glomerular fibrosis.
PMID- 26440365
TI - Serum long non-coding RNA, snoRNA host gene 5 level as a new tumor marker of
malignant melanoma.
PMID- 26440364
TI - PPP2R5C Couples Hepatic Glucose and Lipid Homeostasis.
AB - In mammals, the liver plays a central role in maintaining carbohydrate and lipid
homeostasis by acting both as a major source and a major sink of glucose and
lipids. In particular, when dietary carbohydrates are in excess, the liver
converts them to lipids via de novo lipogenesis. The molecular checkpoints
regulating the balance between carbohydrate and lipid homeostasis, however, are
not fully understood. Here we identify PPP2R5C, a regulatory subunit of PP2A, as
a novel modulator of liver metabolism in postprandial physiology. Inactivation of
PPP2R5C in isolated hepatocytes leads to increased glucose uptake and increased
de novo lipogenesis. These phenotypes are reiterated in vivo, where hepatocyte
specific PPP2R5C knockdown yields mice with improved systemic glucose tolerance
and insulin sensitivity, but elevated circulating triglyceride levels. We show
that modulation of PPP2R5C levels leads to alterations in AMPK and SREBP-1
activity. We find that hepatic levels of PPP2R5C are elevated in human diabetic
patients, and correlate with obesity and insulin resistance in these subjects. In
sum, our data suggest that hepatic PPP2R5C represents an important factor in the
functional wiring of energy metabolism and the maintenance of a metabolically
healthy state.
PMID- 26440366
TI - Follicular Thyroid Carcinoma: How Have Histologic Diagnoses Changed in the Last
Half-Century and What Are the Prognostic Implications?
AB - BACKGROUND: Follicular thyroid carcinoma (FTC) comprises 10% of differentiated
thyroid cancers. Diagnostic controversy and interobserver variability render the
practical diagnosis of FTC difficult. Overall survival rates vary (46-97%). The
aims of this study were to review FTC histologically at the authors' tertiary
care institution and to evaluate long-term survival and recurrence. METHODS:
Diagnostic slides from 66 FTC cases (1965-2007) were reviewed by three
pathologists from two institutions (blinded to clinical outcomes), and consensus
was obtained. Patient demographics, tumor characteristics, and treatment,
survival, and recurrence data were collected. Thyroid cancer-specific and
recurrence-free survival were calculated by original and reclassified diagnoses.
RESULTS: Forty-seven cases (71%) were reclassified: 24 (36%) to papillary thyroid
carcinoma (PTC), 18 (27%) to follicular adenoma (FA), and five (8%) to poorly
differentiated carcinoma (PDC). Nineteen (29%) maintained a diagnosis of FTC. The
extent of surgical resection and rates of radioiodine treatment did not differ by
reclassification diagnosis. Pre-review FTC-specific survival was 83.5% and 75.1%
at 10 and 20 years, respectively. Following contemporary reclassification, FTC
specific survival was 77% and 33.7% at 10 and 20 years, respectively. There were
no cancer-specific deaths in the FA or PTC groups. CONCLUSIONS: Over the past 50
years, changes in our understanding of the pathogenesis, histology, and behavior
of thyroid carcinoma may partially account for the changes in histologic
diagnosis. Elimination of PTC and FA "contaminants" led to decrease in survival
following reclassification. Variability in histologic interpretation contributes
to diagnostic challenges in follicular lesions. Histologic review of thyroid
tumors for research studies is crucial, especially given the ever-changing
diagnostic criteria.
PMID- 26440367
TI - Stem cell research in Latin America: update, challenges and opportunities in a
priority research area.
AB - Stem cell research is attracting wide attention as a promising and fast-growing
field in Latin America, as it is worldwide. Many countries in the region have
defined Regenerative Medicine as a research priority and a focus of investment.
This field generates not only opportunities but also regulatory, technical and
operative challenges. In this review, scientists from Uruguay, Mexico, Chile,
Brazil and Argentina provide their view on stem cell research in each of their
countries. Despite country-specific characteristics, all countries share several
issues such as regulatory challenges. Key initiatives of each country to promote
stem cell research are also discussed. As a conclusion, it is clear that regional
integration should be more emphasized and international collaboration, promoted.
PMID- 26440369
TI - Revisiting dysanapsis: sex-based differences in airways and the mechanics of
breathing during exercise.
AB - NEW FINDINGS: What is the topic of this review? This review focuses on sex-based
differences in the anatomy of the respiratory system, which manifest in
mechanical ventilatory constraints and potentially alter the integrative response
to exercise. What advances does it highlight? Recent evidence indicates that
women have smaller conducting airways than men, even when matched for lung size.
Consequently, women are more likely to experience mechanical ventilatory
constraints to exercise hyperpnoea. Furthermore, at a given ventilation, women
have a higher work and oxygen cost of breathing, both of which may lead to
differences in the whole-body integrative response to dynamic exercise. Our
understanding of the human ventilatory response to exercise is largely based on a
historical body of literature focused primarily on male rather than female
research subjects. In recent years, important sex-based differences in the
anatomy of the human respiratory system have been identified; for a given lung
size, women appear to have smaller-diameter conducting airways than men. The
presence of such inherent differences in the tracheobronchial tree greatly
affects the mechanics of airflow generation, especially during conditions of high
ventilation rates, such as exercise. Data from a growing number of studies
suggest that women may be more susceptible to respiratory system limitations
during exercise than their male counterparts. Specifically, women are more likely
to experience expiratory flow limitation and exercise-induced arterial hypoxaemia
and have a higher metabolic cost of breathing for a given ventilation.
Collectively, the available evidence suggests that sex differences in the
ventilatory response to exercise are present and may have important ramifications
for the integrated response to exercise; however, several fundamental questions
remain unanswered.
PMID- 26440368
TI - Induction of microglial toll-like receptor 4 by prothrombin kringle-2: a
potential pathogenic mechanism in Parkinson's disease.
AB - Microglia-mediated neuroinflammation may play an important role in the initiation
and progression of dopaminergic (DA) neurodegeneration in Parkinson's disease
(PD), and toll-like receptor 4 (TLR4) is essential for the activation of
microglia in the adult brain. However, it is still unclear whether patients with
PD exhibit an increase in TLR4 expression in the brain, and whether there is a
correlation between the levels of prothrombin kringle-2 (pKr-2) and microglial
TLR4. In the present study, we first observed that the levels of pKr-2 and
microglial TLR4 were increased in the substantia nigra (SN) of patients with PD.
In rat and mouse brains, intranigral injection of pKr-2, which is not directly
toxic to neurons, led to the disruption of nigrostriatal DA projections.
Moreover, microglial TLR4 was upregulated in the rat SN and in cultures of the BV
2 microglial cell line after pKr-2 treatment. In TLR4-deficient mice, pKr-2
induced microglial activation was suppressed compared with wild-type mice,
resulting in attenuated neurotoxicity. Therefore, our results suggest that pKr-2
may be a pathogenic factor in PD, and that the inhibition of pKr-2-induced
microglial TLR4 may be protective against degeneration of the nigrostriatal DA
system in vivo.
PMID- 26440370
TI - Community Health Needs Assessment: Potential for Population Health Improvement.
AB - Derived from various health care policies and initiatives, the concept of
population health has been newly adopted by health care and medicine. In
particular, it has been suggested that the Patient Protection and Affordable Care
Act provision that requires nonprofit hospitals to conduct a community health
needs assessment (CHNA) and implement strategies to address health priorities has
the potential to improve population health. A mixed methods study design was used
to examine the potential for population health improvements to occur through the
Internal Revenue Service (IRS)-mandated nonprofit hospital CHNA and planning
processes. Methods involved a 2-phased approach composed of (1) content analysis
of 95 CHNA/implementation strategies reports and (2) interviews with key
informants, consultants, and community stakeholders involved in CHNA and planning
processes. Although this is a great opportunity for the nonprofit hospital
assessment and planning processes to influence population health outcomes, the
findings from the first 3-year assessment and planning cycle (2011-2013) suggest
this is unlikely. As nonprofit hospitals begin the second 3-year assessment and
planning cycle, this article offers recommendations to increase the potential for
nonprofit hospitals to improve population health. These recommendations include
clarifying the purpose of IRS CHNA regulations, engaging community stakeholders
in collaborative assessment and planning, understanding disease etiology and
identifying and addressing broader determinants of health, adopting a public
health assessment and planning model, and emphasizing population health
improvement. (Population Health Management 2016;19:178-186).
PMID- 26440371
TI - Magnetic Resonance Imaging Currently Fails to Fully Evaluate the Biceps-Labrum
Complex and Bicipital Tunnel.
AB - PURPOSE: To determine the diagnostic accuracy of magnetic resonance imaging (MRI)
for biceps-labrum complex (BLC) lesions, including the extra-articular bicipital
tunnel. METHODS: A retrospective review of 277 shoulders with chronic refractory
BLC symptoms that underwent arthroscopic subdeltoid transfer of the long head of
the biceps tendon (LHBT) to the conjoint tendon was conducted. Intraoperative
lesions were categorized as "inside" (labral tears and dynamic LHBT
incarceration), "junctional" (LHBT partial tears, LHBT subluxation, and biceps
chondromalacia), or "bicipital tunnel" (extra-articular bicipital tunnel
scar/stenosis, loose bodies, LHBT instability, and LHBT partial tears) based on
anatomic location. Attending radiologist-generated MRI reports were graded
dichotomously as positive or negative for biceps and labral damage and then
compared with intraoperative findings. Sensitivity, specificity, positive
predictive value (PPV), and negative predictive value (NPV) were calculated for
MRI with respect to intraoperative findings. RESULTS: With regard to inside
lesions, MRI had an overall sensitivity, specificity, PPV, and NPV for labrum
lesions of 77.3%, 68.2%, 57.3%, and 84.5% respectively. The sensitivity,
specificity, PPV, and NPV of MRI for junctional lesions were 43.3%, 55.6%, 73.1%,
and 26.0%, respectively. For the bicipital tunnel, MRI had a sensitivity,
specificity, PPV, and NPV of 50.4%, 61.4%, 48.7%, and 63.0%, respectively.
CONCLUSIONS: MRI was unreliable for ruling out BLC lesions among chronically
symptomatic patients, including when the bicipital tunnel was affected.
PMID- 26440372
TI - A Systematic Review of Meta-analyses Published in Arthroscopy: The Journal of
Arthroscopic and Related Surgery.
AB - PURPOSE: To determine whether the number of meta-analyses published by
Arthroscopy: The Journal of Arthroscopic and Related Surgery has increased from
the inception of the Journal through 2014. METHODS: A literature search of the
Journal's Web site and Medline was carried out. All studies described as a "meta
analysis" as well as systematic reviews that pooled data were included. The
number of published meta-analyses was calculated and summarized by year of
publication, region, topic, and level of evidence. RESULTS: The Journal's Web
site search resulted in 517 citations for review, and the Medline search resulted
in 400. After the results of each search were combined and duplicates were
removed, a total of 60 studies were included in this review. The first published
meta-analysis appeared in 2001. Of the 60 meta-analyses, 36 (60%) were published
between 2013 and 2014. In light of the increase in the number of publications, a
review of the design and conduct of a meta-analysis is presented in a
straightforward question-and-answer format. CONCLUSIONS: The number of meta
analyses appearing in Arthroscopy has increased over the past 2 decades. This
increase highlights the importance of developing an understanding of the premise
and components of a meta-analysis to allow the reader to critically appraise
these studies. LEVEL OF EVIDENCE: Level IV, systematic review of Level I through
IV meta-analyses.
PMID- 26440373
TI - The Relationship Between Tibial Tuberosity-Trochlear Groove Distance and Abnormal
Patellar Tracking in Patients With Unilateral Patellar Instability.
AB - PURPOSE: To evaluate the role of tibial tuberosity-trochlear groove (TT-TG)
distance in patellofemoral kinematics by retrospectively reviewing the dynamic
computed tomography scans of patients with unilateral patellofemoral instability
and comparing unstable and contralateral asymptomatic knees. METHODS: We reviewed
all dynamic computed tomography scans obtained at one tertiary care hospital from
2008 through 2013 and identified 25 patients with a history of recurrent
unilateral patellofemoral instability. During the scans, subjects performed
active knee extension against gravity. Both knees were imaged simultaneously.
Lateral patellar tilt (LPT) and bisect offset (BO) were measured to assess
tracking. TT-TG distance was measured to assess alignment. Measurements were made
in full extension, maximum flexion, and approximately 10 degrees increments in
between. The significance level was set at P < .05. RESULTS: LPT, BO, and TT-TG
distance were highest in extension and decreased with flexion. Measurements were
higher in symptomatic than in asymptomatic knees, with significant differences
identified for LPT, BO, and TT-TG distance at 5 degrees and 15 degrees and for
TT-TG distance at 25 degrees and 35 degrees (P < .05). TT-TG distance was
associated with LPT and BO, with r(2) values in symptomatic knees of 0.55 for TT
TG distance and LPT and of 0.45 for TT-TG distance and BO. CONCLUSIONS: In
patients with unilateral patellar instability, LPT, BO, and TT-TG distance are
higher on the unstable side. An association exists between TT-TG distance and the
tracking parameters studied, suggesting that TT-TG distance relates to patellar
tracking, and a laterally positioned tibial tuberosity may predispose to
instability episodes. LEVEL OF EVIDENCE: Level IV, diagnostic study.
PMID- 26440374
TI - Coevolution of yeast mannan digestion: Convergence of the civilized human diet,
distal gut microbiome, and host immunity.
AB - The complex carbohydrates accessible to the distal gut microbiota (DGM) are key
drivers in determining the structure of this ecosystem. Typically, plant cell
wall polysaccharides and recalcitrant starch (i.e. dietary fiber), in addition to
host glycans are considered the primary nutrients for the DGM; however, we
recently demonstrated that alpha-mannans, highly branched polysaccharides that
decorate the surface of yeast, are also nutrients for several members of
Bacteroides spp. This relationship suggests that the advent of yeast in
contemporary food technologies and the colonization of the intestine by
endogenous fungi have roles in microbiome structure and function. Here we discuss
the process of yeast mannan metabolism, and the intersection between various
sources of intestinal fungi and their roles in recognition by the host innate
immune system.
PMID- 26440375
TI - Preliminary mutagenicity and genotoxicity evaluation of selected arylsulfonamide
derivatives of (aryloxy)alkylamines with potential psychotropic properties.
AB - Determination of the mutagenic and genotoxic liability of biologically active
compounds is of great concern for preliminary toxicity testing and drug
development. In this study, we focused on the evaluation of the mutagenic and
genotoxic effects of selected arylsulfonamide derivatives of aryloxyethyl
piperidines and pyrrolidines (1-8), classified as 5-HT7 receptor antagonist with
antidepressant and procognitive properties, using in silico and in vitro methods:
the Vibrio harveyi assay and the SOS/umu-test (umuC Easy CS test). Finally, the
antimutagenic potential of tested compounds was evaluated with the V. harveyi
assay. It was demonstrated that none of the examined compounds produced a
positive response in in vitro assays and these results were in line with in
silico prediction. Additionally, all the tested compounds demonstrated various
antimutagenic potential, with compound 1 (5-chloro-N-((1-(2
phenoxyethyl)piperidin-4-yl)methyl)thiophene-2-sulfonamide) being the most active
against NQNO-induced mutagenicity.
PMID- 26440376
TI - Time-scales of hydrological forcing on the geochemistry and bacterial community
structure of temperate peat soils.
AB - Peatlands are an important global carbon reservoir. The continued accumulation of
carbon in peatlands depends on the persistence of anoxic conditions, in part
induced by water saturation, which prevents oxidation of organic matter, and
slows down decomposition. Here we investigate how and over what time scales the
hydrological regime impacts the geochemistry and the bacterial community
structure of temperate peat soils. Peat cores from two sites having contrasting
groundwater budgets were subjected to four controlled drought-rewetting cycles.
Pore water geochemistry and metagenomic profiling of bacterial communities showed
that frequent water table drawdown induced lower concentrations of dissolved
carbon, higher concentrations of sulfate and iron and reduced bacterial richness
and diversity in the peat soil and water. Short-term drought cycles (3-9 day
frequency) resulted in different communities from continuously saturated
environments. Furthermore, the site that has more frequently experienced water
table drawdown during the last two decades presented the most striking shifts in
bacterial community structure, altering biogeochemical functioning of peat soils.
Our results suggest that the increase in frequency and duration of drought
conditions under changing climatic conditions or water resource use can induce
profound changes in bacterial communities, with potentially severe consequences
for carbon storage in temperate peatlands.
PMID- 26440377
TI - Dehydrated hereditary stomatocytosis.
PMID- 26440378
TI - Diagnostic utility of NLR or PLR in predicting moderate/severe ovarian
hyperstimulation syndrome: A biochemical aspect.
PMID- 26440380
TI - Chemical recognition of fruit ripeness in spider monkeys (Ateles geoffroyi).
AB - Primates are now known to possess well-developed olfactory sensitivity and
discrimination capacities that can play a substantial role in many aspects of
their interaction with conspecifics and the environment. Several studies have
demonstrated that olfactory cues may be useful in fruit selection. Here, using a
conditioning paradigm, we show that captive spider monkeys (Ateles geoffroyi)
display high olfactory discrimination performance between synthetic odor mixtures
mimicking ripe and unripe fruits of two wild, primate-consumed, Neotropical plant
species. Further, we show that spider monkeys are able to discriminate the odor
of ripe fruits from odors that simulate unripe fruits that become increasingly
similar to that of ripe ones. These results suggest that the ability of spider
monkeys to identify ripe fruits may not depend on the presence of any individual
compound that mark fruit ripeness. Further, the results demonstrate that spider
monkeys are able to identify ripe fruits even when the odor signal is accompanied
by a substantial degree of noise.
PMID- 26440379
TI - Inventory of PCBs in Chicago and Opportunities for Reduction in Airborne
Emissions and Human Exposure.
AB - Urban areas are important regional sources of airborne polychlorinated biphenyls
(PCBs) and population-scale airborne exposure, yet a comprehensive bottom-up
source inventory of PCB emissions has never been quantified at urban scales in
the United States. Here we report a comprehensive parcel level inventory of PCB
stocks and emissions for Chicago, Illinois, developed with a transferable method
from publicly available data. Chicago's legacy stocks hold 276 +/- 147 tonnes
?PCBs, with 0.2 tonnes added annually. Transformers and building sealants
represent the largest legacy categories at 250 and 20 tonnes, respectively. From
these stocks, annual emissions rates of 203 kg for ?PCBs and 3 kg for PCB 11
explain observed concentrations in Chicago air. Sewage sludge drying contributes
25% to emissions, soils 31%, and transformers 21%. Known contaminated sites
account for <1% of stocks and 17% of emissions to air. Paint is responsible for
0.00001% of stocks but up to 7% of ?PCBs emissions. Stocks and emissions are
highly concentrated and not correlated with population density or demographics at
the neighborhood scale. Results suggest that strategies to further reduce
exposure and ecosystem deposition must focus on the largest emissions sources
rather than the most contaminated sites or the largest closed source legacy
stocks.
PMID- 26440381
TI - An ex vivo potency assay to assess active drug levels of a GLP-1 agonistic
peptide during preclinical safety studies.
AB - BACKGROUND: During development of biologics, safety and efficacy assessments are
often hampered by immune responses to the treatment. To assess active exposure of
a drug peptide in a toxicology study, we developed an ex vivo potency assay which
complemented the total drug quantification assay. METHODOLOGY: Compound activity
was assessed in samples of treated monkeys by cell-based cAMP measurements. For
each animal, activity was compared with its predose sample to which the compound
has been added at the postdose concentration as determined by a total LC-MS/MS
assay. CONCLUSION: We were able to show that despite a high total test compound
level, activity was reduced tremendously in antidrug-antibody-positive monkeys.
Therefore, the applied ex vivo potency assay supplements drug quantification
methods to determine active exposures.
PMID- 26440382
TI - Inhibition profiles of mono- and polyvalent FimH antagonists against 10 different
Escherichia coli strains.
AB - Mono- and polyvalent ligands with strong affinities for the mannose-binding
adhesin FimH were synthesised, and their anti-adhesive properties against ten E.
coli strains were compared in two cell-based assays. The compounds were assessed
against the non-pathogenic E. coli K12 and nine strains isolated by coproculture
or from patients with osteoarticular infections (OIs), Crohn's disease (CD) and
urinary tract infections (UTIs). The results showed that the compounds could
inhibit the whole set of bacterial strains but with marked differences in terms
of effective concentrations. The relative inhibitory potency of the monovalent
compounds was also conserved for the ten strains and in the two assays. These
results clearly suggest that a potent monovalent anti-adhesive assessed on a
single E. coli strain will probably be effective on a broad range of strains and
may treat diverse E. coli infections (OIs, CD and UTIs). In contrast, the
polyvalent compounds showed a significant strain-dependancy in preventing E. coli
attachment to intestinal cells. The multivalent antiadhesive effect may therefore
vary depending on the E. coli strain tested.
PMID- 26440383
TI - Early Care and Education Settings Are Vital for Childhood Obesity Prevention.
PMID- 26440384
TI - Predictors of Weight Loss in Young Adults.
AB - BACKGROUND: Increased understanding of weight loss among healthy young people in
naturalistic settings could inform the development of effective weight control
programs. The aim of this study was to describe loss in BMI over 7 years in a
population-based sample of healthy young adolescents (mean age 17 years at
beginning of follow-up) and identify determinants of BMI loss. DESIGN AND METHOD:
Data were available for 681 participants in the Nicotine Dependence in Teens
Study (1999-2012), a longitudinal investigation of adolescents in Montreal
(Canada). Loss in BMI was assessed between age 17 and 24 years. Potential
predictors of BMI loss including age, sex, mother's education, worry about
weight, physical activity, screen time, and cigarette smoking were studied in
multivariable logistic regression. RESULTS: Males and females gained 2.0 and 1.4
BMI units, respectively, on average, between age 17 and 24 years. However, 9% of
males and 14% of females experienced a loss in BMI >=1.0 unit. Female sex and a
higher BMI at age 17 were associated with a higher probability of BMI loss, but
none of age, mother's education, physical activity, screen time, or cigarette
smoking were associated with BMI loss between ages 17 and 24. CONCLUSIONS:
Whereas BMI increased on average between age 17 and 24 years in a population
based sample of healthy young people, 12% of participants experienced a loss in
BMI >=1 unit. Weight loss was highest among the heaviest persons and did not
affect the prevalence of underweight. No single behavior at age 17 stands out as
associated with predicting BMI loss.
PMID- 26440385
TI - Body Mass Index Mediates the Effects of Low Income on Preschool Children's
Executive Control, with Implications for Behavior and Academics.
AB - BACKGROUND: Children from low-income backgrounds are more likely to have
cognitive impairments, academic problems, and obesity. Biological mechanisms for
the relationship between adiposity and neurocognitive functioning have been
suggested, but the direction of effects is unclear. METHODS: The relations among
income, BMI, and cognitive-behavioral functioning were modeled longitudinally.
Children (n = 306) were assessed at 36-39 months (Time 1; T1) and 63-67 months
(Time 4; T4) through anthropometry, measures of executive control (EC), delay
ability (DA), and questionnaires on academic readiness, social competence, and
behavioral adjustment. RESULTS: Income was positively related to T1 EC and DA and
negatively related to T1 BMI. T1 BMI was negatively related to T4 EC, after
controlling for T1 EC, but was unrelated to changes in DA. Neither T1 EC nor DA
was related to changes in BMI. T4 EC predicted greater academic readiness and
social competence and lower adjustment problems at T4. T4 BMI was related to
higher T4 adjustment problems. There was an indirect effect of income on T4 EC
through T1 BMI. There were indirect effects of T1 BMI on academic readiness,
social competence, and adjustment through T4 EC. Children who were obese at T1
had a 19% lower rate of growth of EC, compared to nonobese children. CONCLUSIONS:
BMI mediates the effect of income on children's EC and has negative implications
for academic readiness, social competence, and behavioral adjustment. The dual
impact of obesity and cognitive-behavioral problems underscores the importance of
early identification of and intervention for overweight children which could have
neurocognitive and social-emotional benefits. What's New: BMI mediates the effect
of income on preschoolers' executive control (EC) and has negative implications
for academic readiness and behavioral adjustment. EC and delay ability did not
predict changes in BMI. Early identification of, and intervention for, overweight
children may have neurocognitive and social-emotional benefits.
PMID- 26440387
TI - Characteristics of Youth Presenting for Weight Management: Retrospective National
Data from the POWER Study Group.
AB - BACKGROUND: There are no existing multisite national data on obese youth
presenting for pediatric weight management. The primary aim was to describe BMI
status and comorbidities among youth with obesity presenting for pediatric weight
management (PWM) at programs within the Pediatric Obesity Weight Evaluation
Registry (POWER). METHODS: Data were collected from 2009-2010 among 6737 obese
patients ages 2-17. Patients were classified in three groups by BMI (kg/m(2))
cutoffs and percent of the 95th percentile for BMI: (1) obesity; (2) severe
obesity class 2; and (3) severe obesity class 3. Weighted percentages are
presented for baseline laboratory tests, blood pressure, and demographics.
Generalized logistic regression with clustering was used to examine the
relationships between BMI status and comorbidities. RESULTS: Study youth were
11.6 +/- 3.4 years of age, 56% female, 31% black, 17% Hispanic, and 53% publicly
insured. Twenty-five percent of patients had obesity (n = 1674), 34% (2337) had
severe obesity class 2, and 41% (2726) had severe obesity class 3. Logistic
regression revealed that males (odds ratio [OR], 1.8; 95% confidence interval
[CI], 1.5-2.0), blacks (OR, 1.7; 95% CI, 1.5-2.0), age <6 years (OR, 2.0; 95% CI,
1.5-2.6), and public insurance (OR, 1.8; 95% CI, 1.5-2.0) had a higher odds of
severe obesity class 3. Severe obesity class 3 was associated with higher odds of
laboratory abnormalities for hemoglobin A1c (OR, 1.7; 95% CI, 1.3-2.2), alanine
aminotransferase >=40 U/L (OR, 1.9; 95% CI, 1.3-2.6), and elevated systolic blood
pressure (OR, 2.5; 95% CI, 2.0-3.0). CONCLUSIONS: Youth with obesity need earlier
access to PWM given that they are presenting when they have severe obesity with
significant comorbidities.
PMID- 26440386
TI - Healthier School Environment Leads to Decreases in Childhood Obesity: The Kearney
Nebraska Story.
AB - BACKGROUND: Schools play a role in addressing childhood obesity by implementing
healthy eating and physical activity strategies. The primary aim of this case
study was to describe prevalence of overweight and obesity among elementary
school students in a rural Mid-western community between 2006 and 2012. The
secondary aim was to use a novel approach called "population dose" to
retrospectively evaluate the impact dose of each strategy implemented and its
estimated potential population level impact on changes in overweight and obesity.
METHODS: Weight and height were directly measured annually beginning in January
2006 to assess weight status, using BMI (kg/m(2)), for all kindergarten to fifth
grade students (N ~ 2400 per year). Multiple evidence-based strategies were
implemented in nine schools to increase physical activity and healthy eating
behaviors. BMI reporting and revised school meal programs were implemented
districtwide. Comprehensive school physical activity programs, school food
environment, and supportive/promotional strategies were implemented at individual
schools. RESULTS: The absolute change in prevalence of obesity (BMI >=95th
percentile) decreased from 16.4% to 13.9%, indicating a 15.2% relative change in
prevalence of obesity in 6 years. There was an inverse relationship between the
number of strategies implemented and prevalence of overweight and obesity over
time. CONCLUSIONS: District and school-level approaches have the potential to
impact childhood obesity. Schools can successfully implement strategies to
address overweight and obesity, but the extent of implementation between schools
may vary. Population dose analysis can be used to estimate impact of clusters of
strategies to address overweight/obesity.
PMID- 26440388
TI - Hepatoprotective effect of cold-pressed Syzygium aromaticum oil against carbon
tetrachloride (CCl4)-induced hepatotoxicity in rats.
AB - Contexts: Exposure to environmental pollutants such as carbon tetrachloride
(CCl4) causes liver injuries. There are claims that extracts from Syzygium
aromaticum (Linn.) Merrill & L.M.Perry, (Myrtaceae) protects from such injuries.
OBJECTIVE: This study investigates the protective effects of cold-pressed S.
aromaticum oil (CO) against CCl4-induced liver toxicity in rats. MATERIALS AND
METHODS: CO was orally administered to rats in two doses (100 and 200 mg/kg)
along with CCl4 (1 mL/kg in olive oil) for 8 weeks. Indices of liver and kidney
functions, lipid profile, and peroxidation were evaluated in rats' serum and
tissues. Fatty acids and bioactive lipids of CO were analyzed. RESULTS: High
levels of monounsaturated fatty acids (39.7%) and polyunsaturated fatty acids
(42.1%) were detected in CO. The oil contained high amounts of tocols and
phenolics. The LD50 value at 24 h was approximately 5950 mg/kg. Treatment with
200 mg/kg CO resulted in a decrease of creatinine, urea, and uric acid levels to
0.86, 32.6, and 2.99 mg/dL, respectively. Levels of TL, TC, TAG, LDL-C, and VLDL
C were decreased to 167, 195.3, 584.5, 74.6, and 39.0 mg/L, respectively, after 8
weeks of treatment. Hepatic malondialdehyde levels were reduced and glutathione
levels were elevated in CO-treated rats. CO reduced the activities of AST, ALT,
and ALP as well as kidney function markers, protein, and lipid profiles,
respectively. Histopathological examination of liver indicated that CO treatment
reduced fatty degenerations, cytoplasmic vacuolization, and necrosis. CONCLUSION:
CO possessed a protective effect against CCl4-induced hepatotoxicity in rats,
mediated possibly by the antioxidant properties of the oil.
PMID- 26440389
TI - As I approach the end of my life....
PMID- 26440390
TI - Improving quality of informed consent in clinical research.
PMID- 26440391
TI - Utility of portable monitoring in the diagnosis of obstructive sleep apnea.
AB - Obstructive sleep apnea (OSA) is a common but underdiagnosed sleep disorder,
which is associated with systemic consequences such as hypertension, stroke,
metabolic syndrome, and ischemic heart disease. Nocturnal laboratory-based
polysomnography (PSG) is the gold standard test for diagnosis of OSA. PSG
consists of a simultaneous recording of multiple physiologic parameters related
to sleep and wakefulness including electroencephalography (EEG),
electrooculography (EOG), surface electromyography (EMG), airflow measurement
using thermistor and nasal pressure transducer, pulse oximetry and respiratory
effort (thoracic and abdominal). Multiple alternative and simpler methods that
record respiratory parameters alone for diagnosing OSA have been developed in the
past two decades. These devices are called portable monitors (PMs) and enable
performing sleep studies at a lower cost with shorter waiting times. It has been
observed and reported that comprehensive sleep evaluation coupled with the use of
PMs can fulfill the unmet need for diagnostic testing in various out-of-hospital
settings in patients with suspected OSA. This article reviews the available
medical literature on PMs in order to justify the utility of PMs in the diagnosis
of OSA, especially in resource-poor, high-disease burden settings. The published
practice parameters for the use of these devices have also been reviewed with
respect to their relevance in the Indian setting.
PMID- 26440392
TI - Prevalence of angiotensin converting enzyme (ACE) gene insertion/deletion
polymorphism in South Indian population with hypertension and chronic kidney
disease.
AB - CONTEXT: Chronic Kidney Disease (CKD) is associated with a high risk of
developing further severe complications such as, cardiovascular disease and
eventually End Stage Renal Disease (ESRD) leading to death. Hypertension plays a
key role in the progression of renal failure and is also a chief risk factor for
the occurrence of End Stage Renal Disease (ESRD). AIM: This study investigates
the possible association of insertion (I) and deletion (D) polymorphism of ACE
gene in patients of Chronic Kidney Disease (CKD) with and without hypertension
(HT). SETTINGS AND DESIGN: Total 120 participants with 30 members in each group
(Control, HT, CKD and CKD-HT) were chosen followed by informed consent. MATERIALS
AND METHODS: Blood samples were collected and subjected to biochemical analyses
and nested PCR amplification was performed to genotype the DNA, for ACE I/D using
specific primers. STATISTICAL ANALYSIS: Statistical analyses were performed using
SPSS version 13. Allele and genotypic frequency was calculated by direct gene
counting method. Comparison of the different genotypes was done by using Chi
square test. Odd's ratios were calculated with a 95% confidence interval limit.
RESULTS: The ACE genotype were distributed as II, 27 (90%); DD, 2 (6.67%) and ID,
1 (3.33%) in control, II, 1 (3.33%); DD, 5 (16.67%) and ID, 24 (80%) in HT, II, 4
(13.33%); DD, 24 (80%) and ID, 2 (6.67%) in CKD and II, 0 (0%); DD, 2 (6.67%) and
ID, 28 (93.33%) in CKD-HT group. CONCLUSIONS: D allele of ACE gene confers a
greater role in genetic variations underlying CKD and hypertension. This result
suggest that CKD patients should be offered analysis for defects in ACE I/D
polymorphisms, especially if they are hypertensive.
PMID- 26440393
TI - PIRO concept: staging of sepsis.
AB - INTRODUCTION: Sepsis is common presenting illness to the emergency services and
one of the leading causes of hospital mortality. Researchers and clinicians have
realized that the systemic inflammatory response syndrome concept for defining
sepsis is less useful and lacks specificity. The predisposition, infection (or
insult), response and organ dysfunction (PIRO) staging of sepsis similar to
malignant diseases (TNM staging) might give better information. MATERIALS AND
METHODS: A prospective observational study was conducted in emergency medical
services attached to medicine department of a tertiary care hospital in Northern
India. Patients with age 18 years or more with proven sepsis were included in the
first 24 hours of the diagnosis. Two hundred patients were recruited.
Multivariate logistic regression analysis was done to assess the factors that
predicted in-hospital mortality. RESULTS: Two hundred patients with proven
sepsis, admitted to the emergency medical services were analysed. Male
preponderance was noted (M: F ratio = 1.6:1). Mean age of study cohort was 50.50
+/- 16.30 years. Out of 200 patients, 116 (58%) had in-hospital mortality. In
multivariate logistic regression analysis, the factors independently associated
with in-hospital mortality for predisposition component of PIRO staging were age
>70 years, chronic obstructive pulmonary disease, chronic liver disease, cancer
and presence of foley's catheter; for infection/ insult were pneumonia, urinary
tract infection and meningitis/encephalitis; for response variable were tachypnea
(respiratory rate >20/minute) and bandemia (band >5%). Organ dysfunction
variables associated with hospital mortality were systolic blood pressure <90mm
Hg, prolonged activated partial thromboplastin time, raised serum creatinine,
partial pressure of oxygen in arterial blood/ fraction of inspired oxygen (PaO 2
/FiO 2 ) ratio <300, decreased urine output in first two hours of emergency
presentation and Glasgow coma scale <=9. Each of the components of PIRO had good
predictive capability for in-hospital mortality but the total score was more
accurate than the individual score and increasing PIRO score was associated with
higher in-hospital mortality. The area under receiver operating characteristic
curve for cumulative PIRO staging system as a predictor of in-hospital mortality
was 0.94. CONCLUSION: This study finds PIRO staging as an important tool to
stratify and prognosticate hospitalised patients with sepsis at a tertiary care
center. The simplicity of score makes it more practical to be used in busy
emergencies as it is based on four easily assessable components.
PMID- 26440394
TI - Prevalence of autism spectrum disorders among children (1-10 years of age) -
findings of a mid-term report from Northwest India.
AB - BACKGROUND: India is the second most populous country of the world. A large
portion of the population of this country is below 20 years of age but still
there is a paucity of information about the prevalence and incidence of many
developmental disorders. This study was planned to estimate the prevalence of
autism spectrum disorders (ASDs) in the selected areas (tribal, rural, and urban)
of a northern state of India, Himachal Pradesh. METHODS: A cross-sectional two
phase study was conducted covering all the children in the range of 1-10 years of
age. Phase one included screening of all the children in the age group of 1-10
years, with the help of an indigenous assessment tool for autism. The
sociodemographic profile of the participants was also recorded during phase one.
Phase two involved the clinical evaluation of individuals who were suspected of
autism on screening. RESULTS: The results show a prevalence rate of 0.9/1000. The
highest prevalence rate was observed in the rural area. CONCLUSIONS:
Socioeconomic status (SES) may be one of the fundamental indicators for ASDs in
India.
PMID- 26440395
TI - Intersecting pentagons as surrogate for identifying the use of mini mental state
examination in assessment of dementia in a largely illiterate population.
AB - BACKGROUND AND RATIONALE: The mini-mental state evaluation (MMSE) is often used
to identify patients with dementia. One component of the MMSE is the intersecting
pentagon copying (IPC) test, which may be difficult to be used in an illiterate
population. MATERIALS AND METHODS: A post hoc analysis on an elderly population
(60 years and above) from Himachal Pradesh was carried out. The data of only
1,513 elderly individuals out of a total of 2,000 participants with a score of
more than 26 (nondemented) out of a possible score of 30 on cognitive battery
available were used. The scores on the IPC were evaluated and their association
with some demographic variables was also assessed. RESULTS: Illiterate
participants, female participants, those with greater age, and the rural/tribal
population groups faced the most difficulty in drawing the intersecting pentagons
and even greater difficulty in drawing them correctly. DISCUSSION: The IPC
presents challenges for people who are illiterate and the scoring method needs to
be addressed and changed particularly when the test is used in largely illiterate
populations.
PMID- 26440396
TI - Incidence and factors associated with medication nonadherence in patients with
mental illness: a cross-sectional study.
AB - BACKGROUND: In spite of the progress made in the treatment of psychiatric
disorders during the last few decades, nonadherence continues to be a frequent
phenomenon, often associated with potentially severe clinical consequences and
increased health-care costs. There are numerous factors associated with
medication nonadherence in patients with mental illness. The aim of the study was
to determine the incidence and factors associated with medication nonadherence
among psychiatric outpatients. MATERIALS AND METHODS: A cross-sectional study was
carried out in the outpatient psychiatric department of an Indian tertiary care
private hospital over a period of 1 year. Patients aged 18 years and above who
presented with mental illness as diagnosed by the International Classification of
Diseases (ICD)-10 and who were receiving at least one psychotropic medication for
at least 1 month were included in the study. Medication adherence was assessed
using the Medication Adherence Rating Scale (MARS). RESULTS: Of the 400 patients,
172 (43%) were nonadherent to their prescribed medications. There is a
statistically significant association between the education (P = 0.001), number
of drugs (P = 0.002), family income (P = 0.013), and nonadherence. Among the 172
patients, 33.5 % were nonadherent to their therapy due to patient-related factors
followed by drug-related factors (32%) and disease-related factors (31%).
CONCLUSION: The overall incidence of medication nonadherence in patients with
mental illness was 43%. Numerous factors contributed to medication nonadherence.
Strategies need to be developed and implemented to enhance medication adherence,
and thereby achieve a better therapeutic outcome in patients with mental illness.
PMID- 26440397
TI - An audit of consent refusals in clinical research at a tertiary care center in
India.
AB - BACKGROUND AND RATIONALE: Ensuring research participants' autonomy is one of the
core ethical obligations of researchers. This fundamental principle confers on
every participant the right to refuse to take part in clinical research, and the
measure of the number of consent refusals could be an important metric to
evaluate the quality of the informed consent process. This audit examined consent
refusals among Indian participants in clinical studies done at our center.
MATERIALS AND METHODS: The number of consent refusals and their reasons in 10
studies done at our center over a 5-year period were assessed. The studies were
classified by the authors according to the type of participant (healthy vs
patients), type of sponsor (investigator-initiated vs pharmaceutical industry),
type of study (observational vs interventional), level of risk [based on the
Indian Council of Medical Research (ICMR) "Ethical Guidelines for Biomedical
Research on Human Participants"], available knowledge of the intervention being
studied, and each patient's disease condition. RESULTS: The overall consent
refusal rate was 21%. This rate was higher among patient participants [23.8% vs.
healthy people (14.9%); P = 0.002], in interventional studies [33.6% vs
observational studies (7.5%); P < 0.0001], in pharmaceutical industry-sponsored
studies [34.7% vs investigator-initiated studies (7.2%); P < 0.0001], and in
studies with greater risk (P < 0.0001). The most common reasons for consent
refusals were multiple blood collections (28%), inability to comply with the
study protocol (20%), and the risks involved (20%). CONCLUSION: Our audit
suggests the adequacy and reasonable quality of the informed consent process
using consent refusals as a metric.
PMID- 26440398
TI - Fish gall bladder consumption presenting as acute renal failure.
AB - A forty two year old male was admitted with history of anuria and breathlessness
following consumption of raw rohu fish gall bladder. He had azotemia and required
hemodialysis. His renal failure improved over a period of about four weeks.
Incidences have been reported from South East Asian countries associating
consumption of raw rohu fish gall bladder with acute renal failure.
PMID- 26440399
TI - Conducting evaluation in gestational diabetes.
PMID- 26440400
TI - A case of probable bemiparin-induced heparin-induced thrombocytopenia type II
managed with low-dose fondaparinux.
PMID- 26440401
TI - A novel coumarin derivative, 8-methoxy chromen-2-one alleviates collagen induced
arthritis by down regulating nitric oxide, NFkappaB and proinflammatory
cytokines.
AB - Ruta graveolens (Rue) is a well-known medicinal plant having anti-inflammatory
and other healing properties. This contains many active phytochemicals such as
coumarins which possess anti-inflammatory and anti-cancer activities. The present
study was carried out to evaluate the therapeutic potential of a newly isolated
coumarin derivative from rue plant, 8-methoxy-chromen-2-one (MCO) in the collagen
induced arthritic (CIA) rat model. MCO showed inhibition of cytokines and NF
kappaB in LPS stimulated J774 cells which prompted its possible use in animal. In
CIA, arthritic index and arthritic score reduced markedly within 15days of MCO
treatment at doses of 2mg and 20mg per kg body weight. Alleviation of joint
damage in CIA animals on treatment with MCO was evident from radiographic and
histological data. Behavioral studies by open field tests also showed
convalescence in the MCO treated CIA rats. Further, escalated plasma levels of
pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6, and also nitric oxide
reduced significantly with the treatment. All these results indicate the
therapeutic efficacy of MCO and its possible use as an anti-arthritic drug.
PMID- 26440402
TI - Estrogen upregulates inflammatory signals through NF-kappaB, IFN-gamma, and
nitric oxide via Akt/mTOR pathway in the lymph node lymphocytes of middle-aged
female rats.
AB - The alterations in the secretion of sex steroids, especially estrogen, in females
throughout reproductive life and its decline with age alters the functions of the
neuroendocrine-immune network and renders them susceptible to age-related
diseases and cancers. This study investigates the mechanisms of estrogen-induced
alterations in cell-mediated immune and inflammatory responses in the lymphocytes
from lymph nodes (axillary and inguinal) of ovariectomized (OVX) middle-aged
female rats. Ovariectomized middle-aged (MA) Sprague-Dawley female rats (n=8)
were implanted with 17beta-estradiol (E2) 30-day release pellets (0.6 and
300MUg). At the end of the treatment period, lymph nodes (axillary and inguinal)
were isolated and examined for serum 17beta-estradiol, lymphoproliferation,
cytokine production, expression of p-Akt, p-mTOR, p-IkappaB-alpha and p-NF-kappaB
(p50 and p65), extent of lipid peroxidation, nitric oxide (NO) production,
cytochrome c oxidase activity and reactive oxygen species (ROS) production. There
was an OVX-related decline in serum 17beta-estradiol level, Con A-induced
lymphoproliferation, p-Akt and p-mTOR expression, and cytochrome c oxidase (COX)
activity. E2 supplementation increased serum 17beta-estradiol level,
lymphoproliferation, expression of p-Akt, p-mTOR, p-IkappaB-alpha and p-NF-kappaB
(p50 and p65), lipid peroxidation, IFN-gamma, TNF-alpha, ROS and NO production,
while it decreased IL-6 production. E2 mediates inflammatory responses by
increasing the levels of NO and TNF-alpha by up regulating IFN-gamma and
simultaneously promotes aging through the generation of free radicals as
reflected by increased lipid peroxidation and ROS production in lymph nodes.
These findings may have wide implications to immunity and inflammatory disorders
including autoimmune diseases predominantly prevalent in females.
PMID- 26440403
TI - Charge-transfer crystallites as molecular electrical dopants.
AB - Ground-state integer charge transfer is commonly regarded as the basic mechanism
of molecular electrical doping in both, conjugated polymers and oligomers. Here,
we demonstrate that fundamentally different processes can occur in the two types
of organic semiconductors instead. Using complementary experimental techniques
supported by theory, we contrast a polythiophene, where molecular p-doping leads
to integer charge transfer reportedly localized to one quaterthiophene backbone
segment, to the quaterthiophene oligomer itself. Despite a comparable relative
increase in conductivity, we observe only partial charge transfer for the latter.
In contrast to the parent polymer, pronounced intermolecular frontier-orbital
hybridization of oligomer and dopant in 1:1 mixed-stack co-crystallites leads to
the emergence of empty electronic states within the energy gap of the surrounding
quaterthiophene matrix. It is their Fermi-Dirac occupation that yields mobile
charge carriers and, therefore, the co-crystallites-rather than individual
acceptor molecules-should be regarded as the dopants in such systems.
PMID- 26440405
TI - [Acute compartment syndrome after a bowling game].
AB - A 28-year-old male patient was initially conservatively treated by a general
physician for muscle strain of the right calf after a bowling game. Due to
increasing pain and swelling of the lower leg 5 days later, the differential
diagnosis of a deep vein thrombosis was considered. Furthermore, the onset of
neurological deficits and problems with raising the foot prompted inclusion of
compartment syndrome in the differential diagnosis for the first time. Admission
to hospital for surgical intervention was scheduled for the following day. At
this point in time the laboratory results showed a negative d-dimer value and
greatly increased C-reactive protein level. On day 6 a dermatofasciotomy was
performed which revealed extensive muscular necrosis with complete palsy of the
peroneal nerve. In the following lawsuit the patient accused the surgeon of
having misdiagnosed the slow-onset compartment syndrome and thus delaying correct
and mandatory treatment. The arbitration board ruled that the surgeon should have
performed fasciotomy immediately on day 5 at the patient's consultation. The
clinical presentation of progressive pain, swelling of the lower leg in
combination with peroneal palsy must lead to the differential diagnosis of
compartment syndrome resulting in adequate therapy. The delay of immediate
surgery, therefore, was assessed to be faulty as this knowledge is to be expected
of a surgeon.
PMID- 26440404
TI - Influenza Virus Reassortment Is Enhanced by Semi-infectious Particles but Can Be
Suppressed by Defective Interfering Particles.
AB - A high particle to infectivity ratio is a feature common to many RNA viruses,
with ~90-99% of particles unable to initiate a productive infection under low
multiplicity conditions. A recent publication by Brooke et al. revealed that, for
influenza A virus (IAV), a proportion of these seemingly non-infectious particles
are in fact semi-infectious. Semi-infectious (SI) particles deliver an incomplete
set of viral genes to the cell, and therefore cannot support a full cycle of
replication unless complemented through co-infection. In addition to SI
particles, IAV populations often contain defective-interfering (DI) particles,
which actively interfere with production of infectious progeny. With the aim of
understanding the significance to viral evolution of these incomplete particles,
we tested the hypothesis that SI and DI particles promote diversification through
reassortment. Our approach combined computational simulations with experimental
determination of infection, co-infection and reassortment levels following co
inoculation of cultured cells with two distinct influenza A/Panama/2007/99 (H3N2)
based viruses. Computational results predicted enhanced reassortment at a given %
infection or multiplicity of infection with increasing semi-infectious particle
content. Comparison of experimental data to the model indicated that the
likelihood that a given segment is missing varies among the segments and that
most particles fail to deliver >=1 segment. To verify the prediction that SI
particles augment reassortment, we performed co-infections using viruses exposed
to low dose UV. As expected, the introduction of semi-infectious particles with
UV-induced lesions enhanced reassortment. In contrast to SI particles, inclusion
of DI particles in modeled virus populations could not account for observed
reassortment outcomes. DI particles were furthermore found experimentally to
suppress detectable reassortment, relative to that seen with standard virus
stocks, most likely by interfering with production of infectious progeny from co
infected cells. These data indicate that semi-infectious particles increase the
rate of reassortment and may therefore accelerate adaptive evolution of IAV.
PMID- 26440406
TI - Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in
Treatment-resistant Depression: A Preliminary Study.
AB - BACKGROUND: Although current models of depression suggest that a sequential
modulation of limbic and prefrontal connectivity is needed for illness recovery,
neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing
functional connectivity (FC) before and after an ECT course, without
characterizing functional changes occurring at early treatment phases. OBJECTIVE:
To assess sequential changes in limbic and prefrontal FC during the course of ECT
and their impact on clinical response. METHODS: Longitudinal intralimbic and
limbic-prefrontal networks connectivity study. We assessed 15 patients with
treatment-resistant depression at four different time-points throughout the
entire course of an ECT protocol and 10 healthy participants at two functional
neuroimaging examinations. Furthermore, a path analysis to test direct and
indirect predictive effects of limbic and prefrontal FC changes on clinical
response measured with the Hamilton Rating Scale for Depression was also
performed. RESULTS: An early significant intralimbic FC decrease significantly
predicted a later increase in limbic-prefrontal FC, which in turn significantly
predicted clinical improvement at the end of an ECT course. CONCLUSIONS: Our data
support that treatment response involves sequential changes in FC within regions
of the intralimbic and limbic-prefrontal networks. This approach may help in
identifying potential early biomarkers of treatment response.
PMID- 26440407
TI - Identification of Novel and Conserved microRNAs in Homalodisca vitripennis, the
Glassy-Winged Sharpshooter by Expression Profiling.
AB - The glassy-winged sharpshooter (GWSS) Homalodisca vitripennis (Hemiptera:
Cicadellidae), is a xylem-feeding leafhopper and an important vector of the
bacterium Xylella fastidiosa; the causal agent of Pierce's disease of grapevines.
MicroRNAs are a class of small RNAs that play an important role in the functional
development of various organisms including insects. In H. vitripennis, we
identified microRNAs using high-throughput deep sequencing of adults followed by
computational and manual annotation. A total of 14 novel microRNAs that are not
found in the miRBase were identified from adult H. vitripennis. Conserved
microRNAs were also found in our datasets. By comparison to our previously
determined transcriptome sequence of H. vitripennis, we identified the potential
targets of the microRNAs in the transcriptome. This microRNA profile information
not only provides a more nuanced understanding of the biological and
physiological mechanisms that govern gene expression in H. vitripennis, but may
also lead to the identification of novel mechanisms for biorationally designed
management strategies through the use of microRNAs.
PMID- 26440408
TI - A biomechanical evaluation of CNT-grown bone.
AB - Beside their biochemical properties, the exceptional mechanical characteristics
of carbon nanotubes (CNTs) suggested growing a reinforced composite material very
similar to natural bone in structure and chemical composition, but significantly
stronger and stiffer. This is where biomechanical considerations portray
themselves to justify the need for further investigations, in order to verify the
applicability of CNTs as scaffolds that may ease bone regeneration and
simultaneously raise its mechanical strength and durability. This research, using
several modeling approaches, attempts to look at some of the mechanical changes
likely to take place in the promised artificial tissue, while considering the
relationships between mechanical and living functions of bone, particularly the
remodeling process. Results suggest that notwithstanding the significant
improvements induced to the mechanical behavior of the artificial tissue,
applications of such stiff inclusions as CNTs in reinforcing the material of bone
may detrimentally change the thresholds of mechanical stimuli that are essential
for the initiation and resumption of the bone remodeling process.
PMID- 26440409
TI - A surge of late-occurring meiotic double-strand breaks rescues synapsis
abnormalities in spermatocytes of mice with hypomorphic expression of SPO11.
AB - Meiosis is the biological process that, after a cycle of DNA replication, halves
the cellular chromosome complement, leading to the formation of haploid gametes.
Haploidization is achieved via two successive rounds of chromosome segregation,
meiosis I and II. In mammals, during prophase of meiosis I, homologous
chromosomes align and synapse through a recombination-mediated mechanism
initiated by the introduction of DNA double-strand breaks (DSBs) by the SPO11
protein. In male mice, if SPO11 expression and DSB number are reduced below
heterozygosity levels, chromosome synapsis is delayed, chromosome tangles form at
pachynema, and defective cells are eliminated by apoptosis at epithelial stage IV
at a spermatogenesis-specific endpoint. Whether DSB levels produced in Spo11 (+/
) spermatocytes represent, or approximate, the threshold level required to
guarantee successful homologous chromosome pairing is unknown. Using a mouse
model that expresses Spo11 from a bacterial artificial chromosome, within a Spo11
(-/-) background, we demonstrate that when SPO11 expression is reduced and DSBs
at zygonema are decreased (approximately 40 % below wild-type level), meiotic
chromosome pairing is normal. Conversely, DMC1 foci number is increased at
pachynema, suggesting that under these experimental conditions, DSBs are likely
made with delayed kinetics at zygonema. In addition, we provide evidences that
when zygotene-like cells receive enough DSBs before chromosome tangles develop,
chromosome synapsis can be completed in most cells, preventing their apoptotic
elimination.
PMID- 26440410
TI - Sex chromosome recombination failure, apoptosis, and fertility in male mice.
AB - Lack of crossing-over in meiosis can trigger an apoptotic response at metaphase I
by the spindle assembly checkpoint (SAC). In contrast to females, segregation of
sex chromosomes in males poses a particular challenge as recombination and
chiasma formation is restricted to the pseudoautosomal region, the small region
of homology between X and Y chromosomes. Existing data indicate that low levels
of crossover failure in male meiosis can be tolerated without compromising
fertility, while high levels of X-Y dissociation (in >=70 % of cells) result in
widespread apoptosis and subsequent infertility, demonstrated earlier, e.g., in
Spo11beta-only mice. Here, we explore the threshold of X-Y recombination failure
frequency that is compatible with fertility. We show that in Spo11beta-only(mb)
mice with a mixed genetic background, in contrast to Spo11beta-only mice with a
C57BL/6 background, X-Y pairing fails in ~50 % of cells but this still allows for
sperm production without any overt impact on fertility. We also review data on
apoptosis and fertility from other achiasmate mouse models and propose that the
incidence of homolog dissociation that can be tolerated in vivo without
compromising male fertility lies between 50 and 70 %.
PMID- 26440411
TI - Anti-IL-20 Monoclonal Antibody Suppresses Prostate Cancer Growth and Bone
Osteolysis in Murine Models.
AB - Interleukin (IL)-20 is a proinflammatory cytokine in the IL-10 family. IL-20 is
associated with tumor promotion in the pathogenesis of oral, bladder, and breast
cancer. However, little is known about the role of IL-20 in prostate cancer. We
hypothesize that IL-20 promotes the growth of prostate cancer cells.
Immunohistochemical staining showed that IL-20 and its receptors were expressed
in human PC-3 and LNCaP prostate cancer cell lines and in prostate tumor tissue
from 40 patients. In vitro, IL-20 upregulated N-cadherin, STAT3, vimentin,
fibronectin, RANKL, cathepsin G, and cathepsin K, and increased the migration and
colony formation of prostate cancer cells via activated p38, ERK1/2, AKT, and NF
kappaB signals in PC-3 cells. We investigated the effects of anti-IL-20
monoclonal antibody 7E on prostate tumor growth in vivo using SCID mouse
subcutaneous and intratibial xenograft tumor models. In vivo, 7E reduced tumor
growth, suppressed tumor-mediated osteolysis, and protected bone mineral density
after intratibial injection of prostate cancer cells. We conclude that IL-20 is
involved in the cell migration, colony formation, and tumor-induced osteolysis of
prostate cancer. Therefore, IL-20 might be a novel target for treating prostate
cancer.
PMID- 26440412
TI - Invasion and Colonisation of a Tropical Stream by an Exotic Loricariid Fish:
Indices of Gradual Displacement of the Native Common Pleco (Hypostomus punctatus)
by the Red Fin Dwarf Pleco (Parotocinclus maculicauda) over Fifteen Years.
AB - The introduction of invasive species represents a major threat to the integrity
of stream-dwelling fish populations worldwide, and this issue is receiving
increasing attention from scientists, in particular because of potential impact
on biodiversity. In this study, we analysed the dispersal of an exotic loricariid
fish the red fin dwarf pleco (Parotocinclus maculicauda) in a stream of the
Atlantic Forest biome in coastal south-eastern Brazil and evaluated the effects
of this invasion on the native loricariid common pleco (Hypostomus punctatus).
Specimens were collected at eight sites located along the course of the stream
over a 15-year period. The distribution and density of the two species were
determined by the Successive Removal Method. The introduction of P. maculicauda
occurred in the medium sector of the stream, and during the course of the study,
the species dispersed to new sites further upstream. By the end of the study, it
was found at all points upstream from the original site. Hypostomus punctatus was
registered at all sample sites both before and after the introduction of P.
maculicauda, but its density decreased at all upstream sites after the arrival of
the exotic species. Our analysis shows that colonisation by P. maculicauda seems
to have a negative effect on H. punctatus densities. The maintenance of H.
punctatus densities at the sites not colonised by P. maculicauda reinforces the
conclusion that the colonisation of the stream by the exotic species had
deleterious effects on the density of the resident H. punctatus populations,
either by direct or indirect action.
PMID- 26440414
TI - Fabrication of ultra-thin silicon nanowire arrays using ion beam assisted
chemical etching.
AB - Uniform dispersion of Au-Ag alloy nanoparticles underneath the surface of a Si
wafer is realized via Au film pre-deposition and Ag ion implantation. The Au-Ag
nanoparticles are used as catalysts in metal assisted chemical etching for
fabricating Si nanowire arrays with average diameters of less than 10 nm. We find
that the alloy catalysts introduced by ion implantation are the key to obtaining
thin nanowire arrays and we also demonstrate that SiNWAs with various diameters
could be simply produced by changing the thickness of the pre-deposited Au layer.
Compared with the traditional process, ion beam assisted chemical etching is
proven to be a convenient and efficient approach to fabricate ultra-thin SiNWAs
on a large scale.
PMID- 26440413
TI - Pollen Morphology and Boron Concentration in Floral Tissues as Factors Triggering
Natural and GA-Induced Parthenocarpic Fruit Development in Grapevine.
AB - Parthenocarpic fruit development (PFD) reduces fruit yield and quality in
grapevine. Parthenocarpic seedless berries arise from fruit set without effective
fertilization due to defective pollen germination. PFD has been associated to
micronutrient deficiency but the relation of this phenomenon with pollen
polymorphism has not been reported before. In this work, six grapevine cultivars
with different tendency for PFD and grown under micronutrient-sufficient
conditions were analyzed to determine pollen structure and germination capability
as well as PFD rates. Wide variation in non-germinative abnormal pollen was
detected either among cultivars as well as for the same cultivar in different
growing seasons. A straight correlation with PFD rates was found (R2 = 0.9896),
suggesting that natural parthenocarpy is related to defective pollen development.
Such relation was not observed when PFD was analyzed in grapevine plants exposed
to exogenous gibberellin (GA) or abscissic acid (ABA) applications at pre
anthesis. Increase (GA treatment) or reduction (ABA treatment) in PFD rates
without significative changes in abnormal pollen was determined. Although these
plants were maintained at sufficient boron (B) condition, a down-regulation of
the floral genes VvBOR3 and VvBOR4 together with a reduction of floral B content
in GA-treated plants was established. These results suggest that impairment in B
mobility to reproductive tissues and restriction of pollen tube growth could be
involved in the GA-induced parthenocarpy.
PMID- 26440415
TI - Efficiency of a New Mesh-Type Nebulizer (NE-SM1 NEPLUS) for Intrapulmonary
Delivery of Ipratropium Bromide in Surgical Patients.
AB - This study was aimed to evaluate the efficiency of a new mesh-type nebulizer for
the intrapulmonary delivery of ipratropium bromide in surgical patients under
mechanical ventilation. A total of 20 patients were randomly allocated to receive
0.5 mg ipratropium bromide using either a control (Pariboy SX, Pari, Co.,
Starnberg, Germany, n = 10) or test (NE-SM1 NEPLUS, KTMED INC., Seoul, Korea, n =
10) nebulizer during general anaesthesia. Ipratropium bromide was nebulized
continuously for 20 min. in each group. Plasma concentrations of ipratropium
bromide were obtained from blood samples at preset intervals. Non-compartmental
analysis of ipratropium bromide was performed to compare the efficiency of
pulmonary drug delivery in both nebulizers. Population pharmacokinetic analysis
of ipratropium bromide was performed. Additionally, the noise level during the
nebulizer operation and the aerosol particle size for each device were measured.
The dose-normalized AUC(last) was 0.10 min/L for both nebulizers. The
pharmacokinetics of nebulized ipratropium bromide can be described best by a one
compartment model with first-order absorption. The apparent volume of
distribution and metabolic clearance were 1340 L and 6.78 L/min, respectively.
Type of nebulizer was a significant covariate for absorption rate constant. The
equivalent sound level and median aerosol particle diameter were 35.0 dB and 4.52
MUm for the test nebulizer, and 60.2 dB and 3.85 MUm for the control nebulizer,
respectively. From the standpoint of the dose-normalized AUC(last) , a new
vibrating mesh-type nebulizer shows similar performance in the intrapulmonary
delivery of ipratropium bromide to that of a jet-type nebulizer in surgical
patients.
PMID- 26440417
TI - Current Use of Pain Scores in Dutch Intensive Care Units: A Postal Survey in the
Netherlands.
AB - BACKGROUND: Pain is a common problem for critically ill patients treated in the
intensive care unit (ICU) and can have serious consequences. For this reason, the
appropriate recognition and treatment of pain is of extreme importance. However,
pain assessment in critically ill patients can be challenging because these
patients are often unable to self-report. To identify attitudes and practices
regarding the assessment and management of pain in ICU patients unable to self
report, we surveyed all adult ICUs in the Netherlands. METHODS: A multicenter,
exploratory survey was sent by mail to all adult ICUs in the Netherlands.
RESULTS: Eighty-four of 107 ICUs returned the questionnaire for a response rate
of 79%. In patients able to self-report, 94% (n = 79; 95% confidence interval
[CI], 86.7%-98%) of the ICUs used a standardized pain score. Visual Analog Scale
and Numerical Rating Scale were used in 57% (n = 48; 99.3% CI, 41%-72%) and 48%
(n = 40; 99.3% CI, 33%-64%), respectively. Nonteaching hospitals used pain
assessment tools more often than teaching hospitals (P = 0.012). In patients not
able to self-report, pain assessment tools were used in 19% (n = 16) of the ICUs.
In the ICUs that used behaviorally based scoring systems, the Critical Care Pain
Observation Tool and Behavioral Pain Scale (BPS) were used in 6% (n = 5; 99.5%
CI, 1.1%-17%) and 5% (n = 4; 99.5% CI, 0.1%-15%), respectively. Among Dutch
nurses, nursing opinion was considered the gold standard assessment in 36% (n =
30; 98.8% CI, 23%-50%) of the respondents, even when a patient was able to self
report and pain scales were used. In patients unable to self-report, nurses
judged themselves to be more accurate than a behavioral pain assessment tool in
98% (n = 82; 98.8% CI, 89.7%-99.9%) of the patients. CONCLUSIONS: In the
Netherlands, most ICUs used a standardized pain score in patients able to self
report. Nonteaching hospitals used pain assessment tools more often than teaching
hospitals. In patients unable to self-report, pain is not routinely measured with
a validated behavioral pain assessment tool. Almost all nurses in our survey felt
that their assessment of patient pain was more accurate than behavioral pain
assessment tools in patients unable to self-report. More research is needed to
identify factors preventing more widespread acceptance of validated behavioral
pain scores in patients unable to self-report.
PMID- 26440419
TI - Regulation of the NR2B-CREB-CRTC1 Signaling Pathway Contributes to Circadian Pain
in Murine Model of Chronic Constriction Injury.
AB - BACKGROUND: Numerous clinical investigations have revealed the circadian rhythm
changes in the perception of chronic pain, and most clinical chronic pain types
peak in the night. However, it is still undiscovered whether circadian rhythm of
pain exists in rodents and the specific mechanism that may underlie it. Our study
was conducted to investigate the rhythmic changes of hyperalgesia behavior in a
chronic constrictive injury (CCI) model of rodents and to explore the role of the
N-methyl-d-aspartate receptor 2B (NR2B)-cAMP response element binding protein
(CREB)-CREB-regulated transcription coactivator 1 (CRTC1) signaling pathway in
this pain rhythm. METHODS: A CCI operation was performed to mimic clinical
chronic pain. Paw mechanical withdrawal threshold and paw withdrawal thermal
latency were used to test pain behavior in rats; a von Frey cilia test was used
to test mechanical hyperalgesia in mice at Zeitgeber time (ZT) 4, ZT10, ZT16, and
ZT22 for 14 contiguous days. The relative mRNA and protein expression of NR2B,
CREB and CRTC1 in the suprachiasmatic nuclei and the dorsal horn were measured by
real-time polymerase chain reaction and Western blot. CRTC1 and CREB interference
adenovirus vectors were injected intrathecally at 2 time points, respectively
(ZT12 and ZT0), to further explore the proper time point for pain treatment.
RESULTS: During the period of chronic pain state, the pain behavior of CCI
rodents showed a circadian rhythm with the peak at ZT4 or ZT10 daily. The pain
thresholds were significantly different between the activity period and the rest
period. The expressions of NR2B, CRTC1, and CREB at the spinal level were
consistent with the pain rhythm. The intrathecal treatment with CRTC1 or CREB
interference adenovirus from day 7 to day 9 after CCI surgery markedly improved
pain behaviors. Nevertheless, when given at ZT0, they were both more effective at
relieving peak pain than drugs given at ZT12. CONCLUSIONS: Pain behavior in the
chronic pain of CCI displayed circadian rhythm and was associated with circadian
secretion of pain-related receptors. The NR2B-CREB-CRTC1 signaling pathway may
play a crucial role in this rhythm. Moreover, our results suggest that measures
to relieve pain should be taken before pain reaches its peak.
PMID- 26440418
TI - The Effects of Temperature on Clot Microstructure and Strength in Healthy
Volunteers.
AB - BACKGROUND: Anesthesia, critical illness, and trauma are known to alter
thermoregulation, which can potentially affect coagulation and clinical outcome.
This in vitro preclinical study explores the relationship between temperature
change and hemostasis using a recently validated viscoelastic technique. We
hypothesize that temperature change will cause significant alterations in the
microstructural properties of clot. METHODS: We used a novel viscoelastic
technique to identify the gel point of the blood. The gel point identifies the
transition of the blood from a viscoelastic liquid to a viscoelastic solid state.
Furthermore, identification of the gel point provides 3 related biomarkers: the
elastic modulus at the gel point, which is a measure of clot elasticity; the time
to the gel point (TGP), which is a measure of the time required to form the clot;
and the fractal dimension of the clot at the gel point, df, which quantifies the
microstructure of the clot. The gel point measurements were performed in vitro on
whole blood samples from 136 healthy volunteers over a temperature range of 27
degrees C to 43 degrees C. RESULTS: There was a significant negative correlation
between increases in temperature, from 27 degrees C to 43 degrees C, and TGP (r =
-0.641, P < 0.0005). Conversely, significant positive correlations were observed
for both the elastic modulus at the gel point (r = 0.513, P = 0.0008) and df (r =
0.777, P < 0.0005) across the range of 27 degrees C to 43 degrees C. When
temperature was reduced below 37 degrees C, significant reductions in df and TGP
occurred at <=32 degrees C (Bonferroni-corrected P = 0.0093) and <=29 degrees C
(Bonferroni-corrected P = 0.0317), respectively. No significant changes were
observed when temperature was increased to >37 degrees C. CONCLUSIONS: This study
demonstrates that the gel point technique can identify alterations in clot
microstructure because of changes in temperature. This was demonstrated in slower
forming clots with less structural complexity as temperature is decreased. We
also found that significant changes in clot microstructure occurred when the
temperature was <=32 degrees C.
PMID- 26440416
TI - GIMAP5 Deficiency Is Associated with Increased AKT Activity in T Lymphocytes.
AB - Long-term survival of T lymphocytes in quiescent state is essential to maintain
their cell numbers in secondary lymphoid organs. In mice and in rats, the loss of
functional GTPase of the immune associated nucleotide binding protein 5 (GIMAP5)
causes peripheral T lymphopenia due to spontaneous death of T cells. The
underlying mechanism responsible for the disruption of quiescence in Gimap5
deficient T cells remains largely unknown. In this study, we show that loss of
functional Gimap5 results in increased basal activation of mammalian target of
rapamycin (mTOR), independent of protein phosphatase 2A (PP2A) or AMP-activated
protein kinase (AMPK). Our results suggest that the constitutive activation of
the phosphoinositide 3-kinase (PI3K) pathway may be one of the consequences of
the absence of functional GIMAP5.
PMID- 26440420
TI - The Code of the Street and Violent Versus Property Crime Victimization.
AB - Previous research has shown that individuals who adopt values in line with the
code of the street are more likely to experience violent victimization (e.g.,
Stewart, Schreck, & Simons, 2006). This study extends this literature by
examining the relationship between the street code and multiple types of violent
and property victimization. This research investigates the relationship between
street code-related values and 4 types of victimization (assault, breaking and
entering, theft, and vandalism) using Poisson-based multilevel regression models.
Belief in the street code was associated with higher risk of experiencing
assault, breaking and entering, and vandalism, whereas theft victimization was
not related to the street code. The results suggest that the code of the street
influences victimization broadly--beyond violence--by increasing behavior that
provokes retaliation from others in various forms.
PMID- 26440422
TI - Bilateral Striatopallidodentate Calcinosis associated with Systemic Lupus
Erythematosus: Case report and review of literature.
PMID- 26440423
TI - Neuromyelitis optica spectrum disorder and varicella-zoster infection.
PMID- 26440424
TI - Intermittent ascending muscle spasms and paraparesis associated with diffuse
extradural meningeal cysts.
PMID- 26440426
TI - Fear and time: Fear speeds up the internal clock.
AB - We tested time perception in a bisection task featuring a wide range of durations
(from 0.2 to about 8.0s) and highly arousing stimuli (delivery of an electric
shock). In addition, self-report questionnaire responses and skin conductance
responses were assessed to measure emotional reactivity. Results clearly
demonstrated emotion-related time distortion, as stimulus durations were judged
to be longer in the trials with an electric shock than in those without one. In
addition, this lengthening effect increased with the length of durations. These
findings are consistent with the hypothesis of an arousal-induced speeding up of
the internal clock system.
PMID- 26440427
TI - Trends Form Follows Function: New Ways to Inform and Inspire.
PMID- 26440425
TI - PERIOD3 polymorphism is associated with sleep quality recovery after a mild
traumatic brain injury.
AB - BACKGROUND AND AIM: Mild traumatic brain injury (mTBI) causes transient sleep
disorders and circadian dysrhythmia. One of the clock genes, PERIOD3 (PER3),
regulates the circadian rhythm and contains a genetic polymorphism, namely a
variable-number tandem repeat in the coding area with either four or five
repeats. PER3(5) carriers are inclined to have a morning preference and
associated with higher risk of bipolar disorder and diabetes. This study
investigated the effects of PER3 polymorphism on sleep quality changes after
mTBI. MATERIALS AND METHODS: From May 2012 to May 2014, a total of 96 mTBI
patients completed the baseline (1 week after mTBI) and follow-up (6 weeks after
mTBI) assessments, including the Pittsburgh Sleep Quality Index (PSQI) and
anxiety and depression questionnaires. Statistics were analyzed using the Mann
Whitney U test, Wilcox signed-rank test or chi-squared test. RESULTS: Among the
96 patients, 24 were heterozygous PER3(5) carriers (PER3(4/5)), and the rest of
72 were PER3(5) noncarriers (PER3(4/4)). The subscale of PSQI questionnaire
results indicated that the PER3(5) allele was associated with significant sleep
duration shortening, but improvement in overall sleep quality. Furthermore,
analyzing patients with sleep disturbance at the baseline (PSQI >5) revealed that
only the PER3(5) noncarriers exhibited a significant improvement in overall PSQI
scores. CONCLUSION: PER3(5) carriers exhibited sleep duration shortening and
improved daytime function 6 weeks after mTBI compared with the baseline values.
On the other hand, among poor sleepers, PER3(5) carriers did not embrace a
significant improvement of overall PSQI scores as noncarriers. The underlying
mechanisms and clinical significances must be investigated further.
PMID- 26440421
TI - Emerging immunopharmacological targets in multiple sclerosis.
AB - Inflammatory demyelination of the central nervous system (CNS) is the hallmark of
multiple sclerosis (MS), a chronic debilitating disease that affects more than
2.5 million individuals worldwide. It has been widely accepted, although not
proven, that the major pathogenic mechanism of MS involves myelin-reactive T cell
activation in the periphery and migration into the CNS, which subsequently
triggers an inflammatory cascade that leads to demyelination and axonal damage.
Virtually all MS medications now in use target the immune system and prevent
tissue damage by modulating neuroinflammatory processes. Although current
therapies such as commonly prescribed disease-modifying medications decrease the
relapse rate in relapsing-remitting MS (RRMS), the prevention of long-term
accumulation of deficits remains a challenge. Medications used for progressive
forms of MS also have limited efficacy. The need for therapies that are effective
against disease progression continues to drive the search for novel
pharmacological targets. In recent years, due to a better understanding of MS
immunopathogenesis, new approaches have been introduced that more specifically
target autoreactive immune cells and their products, thus increasing specificity
and efficacy, while reducing potential side effects such as global
immunosuppression. In this review we describe several immunopharmacological
targets that are currently being explored for MS therapy.
PMID- 26440428
TI - Urban Plantings: 'Living Laboratories' for Climate Change Response.
AB - Urban plantings are not only valuable resources for understanding 'urban plant
physiology' but are 'living laboratories' for understanding plant response to
climate change. Therefore, we encourage researchers who currently work in natural
ecosystems to consider how urban plantings could enhance their research into
plant physiological responses to a changing climate.
PMID- 26440429
TI - WOX5 is Shining in the Root Stem Cell Niche.
AB - The WUS-RELATED HOMEOBOX 5 (WOX5) gene is expressed in the quiescent center (QC)
to regulate the columella stem cell (CSC) identity. Three recent reports not only
show how WOX5 is controlled but also highlight the key role of WOX5 in root stem
cell niche maintenance.
PMID- 26440430
TI - Diversity in Plant Breeding: A New Conceptual Framework.
AB - Faced with an accelerating rate of environmental change and the associated need
for a more sustainable, low-input agriculture, the urgent new challenge for crop
science is to find ways to introduce greater diversity to cropping systems.
However, there is a dearth of generic formalism in programs seeking to diversify
crops. In this opinion, we propose a new framework, derived from ecological
theory, that should enable diversity targets to be incorporated into plant
breeding programs. While ecological theory provides criteria for maintaining
diversity and optimizing the production of mixtures, such criteria are rarely
fully realized in natural ecosystems. Conversely, crop breeding should optimize
both agronomic value and the ability of plants to perform and live alongside one
another. This framework represents an opportunity to develop more sustainable
crops and also a radical new way to apply ecological theory to cropping systems.
PMID- 26440431
TI - Histone Acetylation Enzymes Coordinate Metabolism and Gene Expression.
AB - Histone lysine acetylation is well known for being important in the epigenetic
regulation of gene expression in eukaryotic cells. Recent studies have uncovered
a plethora of acetylated proteins involved in important metabolic pathways, such
as photosynthesis and respiration in plants. Enzymes involved in histone
acetylation and deacetylation are being identified as regulators of acetylation
of metabolic enzymes. Importantly, key metabolites, such as acetyl-CoA and
NAD(+), are involved in protein acetylation and deacetylation processes, and
their cellular levels may regulate the activity of histone acetyltransferases
(HAT) and deacetylases (HDAC). Further research is required to determine whether
and how HATs and HDACs sense cellular metabolite signals to control gene
expression and metabolic enzyme activity through lysine acetylation and
deacetylation.
PMID- 26440433
TI - Illuminating Progress in Phytochrome-Mediated Light Signaling Pathways.
AB - Light signals regulate a plethora of plant responses throughout their life cycle,
especially the red and far-red regions of the light spectrum perceived by the
phytochrome family of photoreceptors. However, the mechanisms by which
phytochromes regulate gene expression and downstream responses remain elusive.
Several recent studies have unraveled the details on how phytochromes regulate
photomorphogenesis. These include the identification of E3 ligases that degrade
PHYTOCHROME INTERACTING FACTOR (PIF) proteins, key negative regulators, in
response to light, a better view of how phytochromes inhibit another key negative
regulator, CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), and an understanding of why
plants evolved multiple negative regulators to repress photomorphogenesis in
darkness. These advances will surely fuel future research on many unanswered
questions that have intrigued plant photobiologists for decades.
PMID- 26440432
TI - The Engineered Chloroplast Genome Just Got Smarter.
AB - Chloroplasts are known to sustain life on earth by providing food, fuel, and
oxygen through the process of photosynthesis. However, the chloroplast genome has
also been smartly engineered to confer valuable agronomic traits and/or serve as
bioreactors for the production of industrial enzymes, biopharmaceuticals,
bioproducts, or vaccines. The recent breakthrough in hyperexpression of
biopharmaceuticals in edible leaves has facilitated progression to clinical
studies by major pharmaceutical companies. This review critically evaluates
progress in developing new tools to enhance or simplify expression of targeted
genes in chloroplasts. These tools hold the promise to further the development of
novel fuels and products, enhance the photosynthetic process, and increase our
understanding of retrograde signaling and cellular processes.
PMID- 26440434
TI - Host to a Stranger: Arabidopsis and Fusarium Ear Blight.
AB - Fusarium ear blight (FEB) is a devastating fungal disease of cereal crops.
Outbreaks are sporadic and current control strategies are severely limited. This
review highlights the use of Arabidopsis to study plant-FEB interactions. Use of
this pathosystem has identified natural variation in Fusarium susceptibility in
Arabidopsis, and native plant genes and signalling processes modulating the
interaction. Recent breakthroughs include the identification of plant- and insect
derived small molecules which increase disease resistance, and the use of a host
induced gene silencing (HIGS) construct to silence an important Fusarium gene to
prevent infection. Arabidopsis has also been used to study other fungi that cause
cereal diseases. These findings offer the potential for translational research in
cereals which could yield much-needed novel control strategies.
PMID- 26440435
TI - Gene Networks in Plant Biology: Approaches in Reconstruction and Analysis.
AB - Even though vast amounts of genome-wide gene expression data have become
available in plants, it remains a challenge to effectively mine this information
for the discovery of genes and gene networks, for instance those that control
agronomically important traits. These networks reflect potential interactions
among genes and, therefore, can lead to a systematic understanding of the
molecular mechanisms underlying targeted biological processes. We discuss methods
to analyze gene networks using gene expression data, specifically focusing on
four common statistical approaches used to reconstruct networks: correlation,
feature selection in supervised learning, probabilistic graphical model, and meta
prediction. In addition, we discuss the effective use of these methods for
acquiring an in-depth understanding of biological systems in plants.
PMID- 26440436
TI - Plant-PET Scans: In Vivo Mapping of Xylem and Phloem Functioning.
AB - Medical imaging techniques are rapidly expanding in the field of plant sciences.
Positron emission tomography (PET) is advancing as a powerful functional imaging
technique to decipher in vivo the function of xylem water flow (with (15)O or
(18)F), phloem sugar flow (with (11)C or (18)F), and the importance of their
strong coupling. However, much remains to be learned about how water flow and
sugar distribution are coordinated in intact plants, both under present and
future climate regimes. We propose to use PET analysis of plants (plant-PET) to
visualize and generate these missing data about integrated xylem and phloem
transport. These insights are crucial to understanding how a given environment
will affect plant physiological processes and growth.
PMID- 26440437
TI - Tramadol wound infiltration is not different from intravenous tramadol in
children: a randomized controlled trial.
AB - STUDY OBJECTIVE: The purpose of this trial was to assess if tramadol wound
infiltration is superior to intravenous (IV) tramadol after minor surgical
procedures in children because tramadol seems to have local anesthetic-like
effect. DESIGN: Randomized double-blind controlled trial. SETTING: Postanesthesia
care unit. PATIENTS: Forty children, American Society of Anesthesiologists
physical status I or II, scheduled to elective inguinal hernia repair.
INTERVENTIONS: Children were randomly distributed in 1 of 2 groups: IV tramadol
(group 1) or subcutaneous infiltration with tramadol (group 2). At the end of the
surgery, group 1 received 2 mg/kg tramadol (3 mL) by IV route and 3-mL saline
into the surgical wound; group 2 received 2 mg/kg tramadol (3 mL) into the
surgical wound and 3-mL saline by IV route. MEASUREMENTS: In the postanesthesia
care unit, patients were evaluated for pain intensity, nausea and vomiting, time
to first rescue medication, and total rescue morphine and dipyrone consumption.
MAIN RESULTS: Pain scores measured during the postanesthesia recovery time were
similar between groups. Time to first rescue medication was shorter, but not
statistically significant in the IV group. The total dose of rescue morphine and
dipyrone was also similar between groups. CONCLUSIONS: We concluded that tramadol
was effective in reducing postoperative pain in children, and there was no
difference in pain intensity, nausea and vomiting, or somnolence regarding IV
route or wound infiltration.
PMID- 26440438
TI - Perioperative goal-directed hemodynamic therapy in noncardiac surgery: a
systematic review and meta-analysis.
AB - STUDY OBJECTIVE: Goal-directed fluid therapy (GDHT) has been proposed as a method
to reduce complications and mortality. DESIGN: Meta-analysis of the effects of
perioperative GDHT in adult noncardiac surgery on mortality and postoperative
complications was performed using the PRISMA methodology. A systematic search was
performed in MEDLINE, PubMed, EMBASE, and the Cochrane Library (last update,
October 2014). Inclusion criteria were as follows: randomized clinical trials
(RCTs) in which perioperative GDHT was compared with conventional fluid
management in noncardiac surgery. Exclusion criteria were as follows: trauma and
pediatric surgery studies. End points were mortality and number of patients with
complications. SETTING: District general hospital. PATIENTS: Thirty-nine RCTs
were initially identified, with 8 fulfilling the inclusion criteria. Two RCTs
were added by manual search, resulting in 10 RCTs in the final analysis,
including 1527 patients. MEASUREMENTS: Those studies that fulfilled the entry
criteria were examined in full and subjected to quantifiable analysis, predefined
subgroup analysis (stratified by supraphysiological or physiological hemodynamic
goal and by time the intervention was carried out, perioperative or
postoperative), and predefined sensitivity analysis. MAIN RESULTS: A significant
reduction was observed in mortality associated with GDHT compared with
conventional fluid therapy (risk ratio, 0.63; 95% confidence interval, 0.42-0.94;
P = .02). However, no differences were found in the number of patients with
complications (risk ratio, 0.75; 95% confidence interval, 0.50-1.17; P = .21),
and the sensitivity analysis did not confirm the results. CONCLUSIONS: This meta
analysis, with its limitations, shows that the use of perioperative GDHT may
reduce postoperative mortality, but it is unable to show a reduction in the
number of patients with complications.
PMID- 26440439
TI - Automated pulse pressure variation display in the operating room and in the
intensive care unit.
PMID- 26440440
TI - Modified jaw-thrust maneuver to insert laryngeal tube suction.
PMID- 26440441
TI - Analgesic effect and pharmacological mechanism of fentanyl and butorphanol in a
rat model of incisional pain.
AB - OBJECTIVES: To explore analgesic effects of fentanyl and butorphanol on
incisional pain in rats and to investigate the pharmacological mechanism of
combination. METHODS: Seventy rats were randomly divided into control group
(group N, n = 10), fentanyl group (group F, n = 30), and butorphanol group (group
B, n = 30), to determine median effective dose (ED50) in fentanyl and
butorphanol. Another 50 rats were treated with both fentanyl and butorphanol
(joint group) to quantitatively detect response rate of joint application. Ninety
rats were randomly divided into 1/4 ED50 fentanyl (group 1, n = 30), 1/2 ED50
fentanyl (group 2, n = 30), and 3/4 ED50 fentanyl (group 3, n = 30), to detect
the correlation between combined pharmacological effects of 2 drugs and their
dose proportionality. Statistical analysis was performed using SPSS 17.0.
RESULTS: Probit analysis revealed that ED50 of fentanyl was 4.1 MUg/kg, whereas
ED50 of butorphanol was 295 MUg/kg. The qualitative response rate of combination
(Po) was 0.84, and expected qualitative response rate (Pe) was 0.75, with no
statistical significance (P = 0.3). Furthermore, probit analysis showed that 155
MUg/kg butorphanol with 1/4 ED50 fentanyl could reach experimental ED50 of
combination of 2 drugs; 115 MUg/kg butorphanol with 1/2 ED50 fentanyl could reach
experimental combination ED50; and 88 MUg/kg butorphanol with 3/4 ED50 fentanyl
could reach experimental combination ED50. CONCLUSION: Both fentanyl and
butorphanol showed good analgesic effect on incisional pain in rats, but fentanyl
was superior to butorphanol. The pharmacological mechanism of combination with
ED50 of fentanyl and butorphanol showed independent joint action, and the
combination efficacy was related to the dosage.
PMID- 26440442
TI - Successful LMA-ProSeal insertion using a tracheal tube introducer in a patient
with severe rheumatoid arthritis.
PMID- 26440443
TI - Hepatocyte growth factor/c-met promotes proliferation, suppresses apoptosis, and
improves matrix metabolism in rabbit nucleus pulposus cells in vitro.
AB - The etiology of intervertebral disc (IVD) degeneration is closely related to
apoptosis and extracellular matrix degradation in nucleus pulposus (NP) cells.
These defects in NP cells are induced by excessive external stressors such as
reactive oxygen species (ROS) and inflammatory cytokines. Recently, hepatocyte
growth factor (HGF) has been shown to repair damage in various diseases through
anti-apoptotic and anti-inflammatory activity. In this study, we investigated the
effects of HGF on NP cell abnormality caused by ROS and inflammatory cytokines by
using primary NP cells isolated from rabbit IVD. HGF significantly enhanced the
proliferation of NP cells. Apoptosis of NP cells induced by H2 O2 or TNF-alpha
was significantly inhibited by HGF. Induction of mRNA expression of the
inflammation mediators cyclooxygenase-2 and matrix metalloproteinase-3 and -9 by
TNF-alpha was significantly suppressed by HGF treatment. Expression of c-Met, a
specific receptor for HGF, was confirmed in NP cells and was increased by TNF
alpha, suggesting that inflammatory cytokines increase sensitivity to HGF. These
findings demonstrate that activation of HGF/c-Met signaling suppresses damage
caused by ROS and inflammation in NP cells through multiple pathways. We further
suggest the clinical potential of HGF for counteracting IVD degradation involved
in NP cell abnormalities.
PMID- 26440444
TI - Cefcapene Pivoxil Hydrochloride Is a Potentially New Treatment for Palmoplantar
Pustulosis with Pustulotic Arthro-Osteitis.
AB - Pustulosis palmaris et plantaris or palmoplantar pustulosis (PPP) is a refractory
pustular eruption of the palms and soles with unknown etiology. In addition to
skin lesions, PPP patients may present with severe joint pain and pustulotic
arthro-osteitis (PAO), especially of the sternoclavicular joint. PAO is sometimes
regarded as a variant of synovitis, acne, pustulosis, hyperostosis and osteitis
(SAPHO) syndrome. Hence, macrolide and tetracycline antibiotics are used for the
treatment of PPP with PAO. We report 3 cases of PPP with PAO that did not improve
upon administration of macrolide antibiotics with NSAIDs. After administration of
cefcapene pivoxil hydrochloride (CFPN-PI), a third-generation cephalosporin, the
swelling and sternoclavicular joint pain were promptly reduced and dramatically
improved in all 3 cases. We review the conventional antibiotic treatments used
currently and propose CFPN-PI as a potentially new therapy for PPP or PPP + PAO.
PMID- 26440445
TI - Detecting glaucomatous change in visual fields: Analysis with an optimization
framework.
AB - Detecting glaucomatous progression is an important aspect of glaucoma management.
The assessment of longitudinal series of visual fields, measured using Standard
Automated Perimetry (SAP), is considered the reference standard for this effort.
We seek efficient techniques for determining progression from longitudinal visual
fields by formulating the problem as an optimization framework, learned from a
population of glaucoma data. The longitudinal data from each patient's eye were
used in a convex optimization framework to find a vector that is representative
of the progression direction of the sample population, as a whole. Post-hoc
analysis of longitudinal visual fields across the derived vector led to optimal
progression (change) detection. The proposed method was compared to recently
described progression detection methods and to linear regression of instrument
defined global indices, and showed slightly higher sensitivities at the highest
specificities than other methods (a clinically desirable result). The proposed
approach is simpler, faster, and more efficient for detecting glaucomatous
changes, compared to our previously proposed machine learning-based methods,
although it provides somewhat less information. This approach has potential
application in glaucoma clinics for patient monitoring and in research centers
for classification of study participants.
PMID- 26440446
TI - Synthesis, Theoretical Analysis, and Experimental pKa Determination of a
Fluorescent, Nonsymmetric, In-Out Proton Sponge.
AB - Herein, we report the synthesis and theoretical investigation of a nonsymmetric
bis(diisopropylamino)cyclopropenimine (DAC)-functionalized proton sponge
derivative, coined the "Janus" sponge. The reported sponge was isolated as a
monoprotonated salt, though no intramolecular hydrogen bond was observed.
Homodesmotic equations supported the absence of a N-HN intramolecular hydrogen
bond and a relatively low freebase strain, while DFT calculations and X-ray
crystallography revealed the presence of a hydrogen bond to the Cl(-) counterion.
Associated with this fact was the rare in-out geometry of the basic nitrogens,
which represents the first such instance in a proton sponge not having an ortho
substituent and/or being in a protonated state. Furthermore, NLP donation into
the cyclopropenium cation was found to stabilize this unprecedented in-out
geometry. The measured pKa was determined to be 23.8, in good agreement with the
computed value of 23.9. Lastly, the Janus sponge was found to have fluorescent
properties both in the solid state and in solution, which notably represents the
first example of a cyclopropenimine-based fluorescent organic compound.
PMID- 26440447
TI - Timing of Adjuvant Radiotherapy in Glioblastoma Patients: A Single-Institution
Experience With More Than 400 Patients.
AB - BACKGROUND: The standard of care for patients with newly diagnosed glioblastoma
(GBM) is maximal safe resection followed by adjuvant radiation therapy (RT) and
temozolomide (TMZ). OBJECTIVE: To investigate whether the timing of adjuvant RT
after surgery affected outcome in patients with GBM. METHODS: We retrospectively
reviewed all patients with a diagnosis of GBM at our institution. A total of 447
patients were included in our analysis. Patients were divided into 3 equal groups
based on the interval between surgery and RT. The primary outcome was overall
survival (OS). RESULTS: Patients who began RT less than 21 days after surgery
tended to be older, have a lower a Karnofsky Performance Status score, and higher
recursive partitioning analysis class. These patients were more likely to have
undergone biopsy only and received 3-dimensional conformal RT or 2-dimensional
RT. The median OS for patients who started RT less than 21 days after surgery,
between 21 and 32 days after surgery, and more than 32 days after surgery was
374, 465, and 478 days, respectively (P = .004). On multivariate Cox regression
analysis, Karnofsky Performance Status score lower than 70, undergoing biopsy
only, recursive partitioning analysis classes IV and V/VI, use of less than 36 Gy
RT, and lack of TMZ chemotherapy were predictors of worse OS. The interval
between surgery and RT was not significantly associated with OS on multivariate
analysis. CONCLUSION: Patients who begin RT less than 21 days after surgery tend
to have worse prognostic factors than those who begin RT later. When accounting
for significant covariates, the effect of timing between surgery and RT is not
significant.
PMID- 26440448
TI - Effects of dietary quercetin on performance and cytochrome P450 expression of the
cotton bollworm, Helicoverpa armigera.
AB - Quercetin is ubiquitous in terrestrial plants. The cotton bollworm Helicoverpa
armigera as a highly polyphagous insect has caused severe crop losses. Until now,
interactions between this pest and quercetin are poorly understood at the
biochemical and molecular levels. In this study, we investigated the in vivo
effects of quercetin on performance of cotton bollworm and on cytochrome P450
(P450) expression. Deleterious effects of quercetin on the performance of the
cotton bollworm, including growth, survival, pupation and adult emergence were
observed after oral administration of 3 and 10 mg g(-1) quercetin to larvae since
the third instar, whereas no significant toxic effect was found at 0.1 mg g(-1)
quercetin treatment. Piperonyl butoxide treatment enhanced the toxicity of
quercetin. In vitro metabolism studies showed that quercetin was rapidly
transformed by gut enzymes of fifth instar larvae of the cotton bollworm. qRT-PCR
results revealed that the effect of quercetin on P450 expression was tissue- and
dose-specific. Quercetin regulated P450 expression in a mild manner, and it could
serve as P450 inducer (CYP337B1, CYP6B6) or repressor (CYP337B1, CYP6B7, CYP6B27,
CYP9A14, CYP6AE11, and CYP4M7). These findings are important for advancing our
understanding of the biochemical and molecular response of insects to plant
toxins and have implications for a smart pest control.
PMID- 26440449
TI - An examination of the stability of interpersonal hostile-dominance and its
relationship with psychiatric symptomatology and post-discharge aggression.
AB - The relevance of interpersonal hostile-dominance (HD) to post-discharge
aggression in mental health patients is unclear. This study assessed whether (1)
HD is stable over time; (2) the relationship between HD and positive, negative,
disorganized, and excited symptoms is consistent over time; and (3) HD is related
to aggression post-discharge. Two hundred psychiatric inpatients were recruited
on admission to hospital; 41 were available for follow-up at 6 months post
discharge, including 29 men and 12 women, with an age range of 19-63 (M = 39.63
years, SD = 12.69 years). Psychiatric symptomatology and interpersonal style were
assessed at recruitment and follow-up; aggression in the community post-discharge
was measured at follow-up. Results showed that (1) HD was stable over time
despite an overall reduction in psychiatric symptoms, (2) HD was positively
correlated with symptom severity at both time points, and (3) higher HD, excited
symptoms, and positive symptoms measured in the community, and more severe
positive symptoms measured in hospital, were associated with aggressive behavior
post-discharge. These results suggest that HD is a risk factor for more severe
psychopathology. Furthermore, HD, positive symptoms, and excited symptoms
measured in the community act as risk factors for aggressive behavior post
discharge. As such, treatment planning and risk assessment should consider HD.
Aggr. Behav. 42:324-332, 2016. (c) 2015 Wiley Periodicals, Inc.
PMID- 26440451
TI - Experimental and Theoretical Study of an Intramolecular CF3-Group Shift in the
Reactions of alpha-Bromoenones with 1,2-Diamines.
AB - The reactions of trifluoromethylated 2-bromoenones and N,N'-dialkyl-1,2-diamines
have been studied. Depending on the structures of the starting compounds, the
formation of 2-trifluoroacetylpiperazine or 3-trifluoromethylpiperazine-2-ones
was observed. The mechanism of the reaction is discussed in terms of multistep
processes involving sequential substitution of bromine in the starting alpha
bromoenones and intramolecular cyclization of the captodative aminoenones as key
intermediates to form the target heterocycles. The results of theoretical
calculations are in perfect agreement with the experimental data. The unique role
of the trifluoromethyl group in this reaction is demonstrated.
PMID- 26440450
TI - Imaging beta-amyloid using [(18)F]flutemetamol positron emission tomography: from
dosimetry to clinical diagnosis.
AB - In Alzheimer's disease (AD), the deposition of beta-amyloid (Abeta) is
hypothesized to result in a series of secondary neurodegenerative processes,
leading ultimately to synaptic dysfunction and neuronal loss. Since the advent of
the first Abeta-specific positron emission tomography (PET) ligand, (11)C
Pittsburgh compound B ([(11)C]PIB), several (18)F ligands have been developed
that circumvent the limitations of [(11)C]PIB tied to its short half-life. To
date, three such compounds have been approved for clinical use by the US and
European regulatory bodies, including [(18)F]AV-45 ([(18)F]florbetapir;
AmyvidTM), [(18)F]-BAY94-9172 ([(18)F]florbetaben; NeuraceqTM) and [(18)F]3'-F
PIB ([(18)F]flutemetamol; VizamylTM). The present review aims to summarize and
discuss the currently available knowledge on [(18)F]flutemetamol PET. As the
(18)F analogue of [(11)C]PIB, [(18)F]flutemetamol may be of use in the
differentiation of AD from related neurodegenerative disorders and may help with
subject selection and measurement of target engagement in the context of clinical
trials testing anti-amyloid therapeutics. We will also discuss its potential use
in non-AD amyloidopathies.
PMID- 26440452
TI - Meta-Atom Behavior in Clusters Revealing Large Spin Ground States.
AB - The field of single molecule magnetism remains predicated on super- and double
exchange mechanisms to engender large spin ground states. An alternative approach
to achieving high-spin architectures involves synthesizing weak-field clusters
featuring close M-M interactions to produce a single valence orbital manifold.
Population of this orbital manifold in accordance with Hund's rules could
potentially yield thermally persistent high-spin ground states under which the
valence electrons remain coupled. We now demonstrate this effect with a reduced
hexanuclear iron cluster that achieves an S = 19/2 (chi(M)T ~ 53 cm(3) K/mol)
ground state that persists to 300 K, representing the largest spin ground state
persistent to room temperature reported to date. The reduced cluster displays
single molecule magnet behavior manifest in both variable-temperature zero-field
(57)Fe Mossbauer and magnetometry with a spin reversal barrier of 42.5(8) cm(-1)
and a magnetic blocking temperature of 2.9 K (0.059 K/min).
PMID- 26440453
TI - Microglial Janus kinase/signal transduction and activator of transcription 3
pathway activity directly impacts astrocyte and spinal neuron characteristics.
AB - After peripheral nerve injury microglial reactivity change in the spinal cord is
associated with an early activation of Janus kinase (JAK)/STAT3 transduction
pathway whose blockade attenuates local inflammation and pain hypersensitivity.
However, the consequences of microglial JAK/STAT3-mediated signaling on
neighboring cells are unknown. Using an in vitro paradigm we assessed the impact
of microglial JAK/STAT3 activity on functional characteristics of astrocytes and
spinal cord neurons. Purified rat primary microglia was stimulated with JAK/STAT3
classical activator interleukin-6 in the presence or absence of a selective STAT3
inhibitor and rat primary astrocytes or spinal cord neurons were exposed to
microglia conditioned media (CM). JAK/STAT3 activity-generated microglial CM
modulated both astrocyte and neuron characteristics. Beyond inducing mRNA
expression changes in various targets of interest in astrocytes and neurons,
microglia CM activated c-Jun N-terminal kinase, STAT3 and NF-kappaB intracellular
pathways in astrocytes and promoted their proliferation. Without modifying
neuronal excitability or survival, CM affected the nerve processes morphology and
distribution of the post-synaptic density protein 95, a marker of glutamatergic
synaptic contacts. These findings show that JAK/STAT3 activity in microglia
impacts the functional characteristics of astrocytes and neurons. This suggests
its participation in spinal cord tissue plasticity and remodeling occurring after
peripheral nerve injury. We show that the activity of JAK/STAT3 pathway in
microglial cells confers them a specific signaling modality toward neighboring
cells, promoting astrocyte proliferation and changes in neuronal morphology.
These in vitro data suggest that the early JAK/STAT3 activation in spinal cord
microglia, associated with peripheral nerve injury, participates in functional
alteration of various cell populations and in spinal tissue remodeling.
PMID- 26440454
TI - Wrinkled Graphene Monoliths as Superabsorbing Building Blocks for
Superhydrophobic and Superhydrophilic Surfaces.
AB - Superhydrophobic and superhydrophilic surfaces are of great interest because of a
large range of applications, for example, as antifogging and self-cleaning
coatings, as antibiofouling paints for boats, in metal refining, and for water
oil separation. An aqueous ink based on three-dimensional graphene monoliths (Gr)
can be used for constructing both superhydrophobic and superhydrophilic surfaces
on arbitrary substrates with different surficial structures from the meso- to the
macroscale. The surface wettability of a Gr-coated surface mainly depends on
which additional layers (air for a superhydrophobic surface and water for a
superhydrophilic surface) are adsorbed on the surface of the graphene sheets.
Switching a Gr-coated surface between being superhydrophobic and superhydrophilic
can thus be easily achieved by drying and prewetting with ethanol. The Gr-based
superhydrophobic membranes or films should have great potential as efficient
separators for fast and gravity-driven oil-water separation.
PMID- 26440456
TI - A patient with suspected non-ST elevation acute myocardial infarction and
remarkably high brain natriuretic peptide levels.
PMID- 26440455
TI - Sustained effect of health insurance and facility quality improvement on blood
pressure in adults with hypertension in Nigeria: A population-based study.
AB - BACKGROUND: Hypertension is a leading risk factor for death in sub-Saharan
Africa. Quality treatment is often not available nor affordable. We assessed the
effect of a voluntary health insurance program, including quality improvement of
healthcare facilities, on blood pressure (BP) in hypertensive adults in rural
Nigeria. METHODS: We compared changes in outcomes from baseline (2009) to midline
(2011) and endline (2013) between non-pregnant hypertensive adults in the
insurance program area (PA) and a control area (CA), through household surveys.
The primary outcome was the difference between the PA and CA in change in BP,
using difference-in-differences analysis. RESULTS: Of 1500 eligible households,
1450 (96.7%) participated, including 559 (20.8%) hypertensive individuals, of
which 332 (59.4%) had follow-up data. Insurance coverage increased from 0% at
baseline to 41.8% at endline in the PA and remained under 1% in the CA. The PA
showed a 4.97 mm Hg (95% CI: -0.76 to +10.71 mm Hg) greater decrease in systolic
BP and a 1.81 mm Hg (-1.06 to +4.68 mm Hg) greater decrease in diastolic BP from
baseline to endline compared to the CA. Respondents with stage 2 hypertension
showed an 11.43 mm Hg (95% CI: 1.62 to 21.23 mm Hg) greater reduction in systolic
BP and 3.15 mm Hg (-1.22 to +7.53 mm Hg) greater reduction in diastolic BP in the
PA compared to the CA. Attrition did not affect the results. CONCLUSION: Access
to improved quality healthcare through an insurance program in rural Nigeria was
associated with a significant longer-term reduction in systolic BP in subjects
with moderate or severe hypertension.
PMID- 26440457
TI - Stent collapse after guide extension catheter collision. Signature procedural
finding by optical coherence tomography.
PMID- 26440460
TI - Prioritized outcomes to evaluate the effectiveness of atrial fibrillation disease
management: A systematic review and Delphi study.
PMID- 26440459
TI - LASSBio-1425, an analog of thalidomide, decreases triglyceride and increases HDL
cholesterol levels by inhibition of TNF-alpha production.
PMID- 26440458
TI - HbA1c and all-cause mortality risk among patients with type 2 diabetes.
AB - BACKGROUND: Several prospective studies have evaluated the association between
glycosylated hemoglobin (HbA1c) and death risk among diabetic patients. However,
the results have been inconsistent. METHODS: We performed a prospective study
which included 13,334 men and 21,927 women with type 2 diabetes. Cox proportional
hazards regression models were used to estimate the association of different
levels of HbA1c with all-cause mortality. RESULTS: During a mean follow up of 8.7
years, 4199 (2082 men and 2117 women) patients died. The multivariable-adjusted
hazard ratios (HRs) of all-cause mortality associated with different levels of
HbA1c at baseline (<6.0%, 6.0-6.9% [reference], 7.0-7.9, 8.0-8.9%, 9.0-9.9%, 10.0
10.9%, and >=11.0%) were 1.06, 1.00, 1.10, 0.93, 1.26, 1.18 and 1.31 (Pnon
linear=0.008) for men, and 1.21, 1.00, 1.01, 1.08, 1.30, 1.30 and 1.74 (Pnon
linear<0.001) for women, respectively. The J-shaped association of HbA1c with all
cause mortality was confirmed among African American and white diabetic patients,
patients who were more than 50 years old, never smoked or used insulin. When we
used an updated mean value of HbA1c, the J-shaped association of HbA1c with the
risk of all-cause mortality did not change. CONCLUSIONS: Our study demonstrated a
J-shaped association between HbA1c and the risk of all-cause mortality among men
and women with type 2 diabetes. Both high and low levels of HbA1c were associated
with an increased risk of all-cause mortality.
PMID- 26440461
TI - The impact of dual antiplatelet therapy duration on primary composite endpoint
after drug-eluting stent implantation: A meta-analysis of 10 randomized trials.
PMID- 26440462
TI - HMGB1: A promising therapeutic approach for atherosclerosis.
PMID- 26440463
TI - Multisector-reconstruction in 1st generation 320-slice CT at high pulsation-rates
achieved accurate-evaluation of coronary-lumen patency after insertion of a
XIENCE stent. XIENCE Phantom Study Part 4.
PMID- 26440464
TI - The relationship of body mass index to blood pressure levels among children and
adolescents in 30 provinces in China.
PMID- 26440465
TI - Defined daily dose (DDD) and its potential use in clinical trials of resistant
hypertension.
PMID- 26440466
TI - Levosimendan as an adjunctive therapy to MitraClip implantation in patients with
severe mitral regurgitation and left ventricular dysfunction.
PMID- 26440467
TI - Preadmission treatment with sulfonylureas and infarct size after ST-elevation
myocardial infarction.
PMID- 26440468
TI - Intra-aortic balloon pump therapy for acute myocardial infarction: Trial
sequential analysis.
PMID- 26440469
TI - Interleukin-18 disruption suppresses hypoxia-induced pulmonary artery
hypertension in mice.
PMID- 26440470
TI - Comparison of endothelium-dependent and -independent vasomotor response after
abluminal biodegradable polymer biolimus-eluting stent and persistent polymer
everolimus-eluting stent implantation (COMPARE-IT).
AB - BACKGROUND: Drug-eluting stents (DES) have been associated with local endothelial
dysfunction in the segments proximal and distal to the stent (peristent segments)
and increased thrombotic risk in long term follow-up. Little data exists on
endothelial function post-implantation of new DES with biodegradable polymer. The
aim of our study was to compare the local endothelial function assessed by
exercise induced coronary vasomotion after implantation of a biolimus A9-eluting
stent with biodegradable polymer (BES) with an everolimus-eluting stent with
durable polymer (EES). METHODS: Coronary vasomotion was evaluated with
quantitative coronary angiography at rest and during supine bicycle exercise in
nine patients with EES and thirteen patients with BES, 16 months after stent
implantation. Mean luminal diameter of the stent, peristent segments, and of a
control vessel were determined at rest, during exercise, and after the
administration of nitroglycerine. RESULTS: The control vessel showed exercise
induced vasodilatation in both groups (EES: +6.4+/-5.5%, p=0.07; BES: +7.8+/
10.1%, p=0.07). Vasomotion in the stented vessel segment was abolished. There was
exercise-induced vasoconstriction in both groups in the segments proximal (EES:
9.6+/-4.5%; p=0.03; BES: -4.3+/-5.4%, p=0.02) and distal to the stent (EES:
3.2+/-9.3%; p=0.41, BES -8.6+/-8.0%, p<0.01). Sublingual nitroglycerin was
associated with maximal vasodilatation of the peristent segments in both groups.
CONCLUSION: Alike DES with durable polymer, stents with a biodegradable polymer
are associated with exercise-induced paradoxical coronary vasoconstriction of the
peristent segments. This data suggests that endothelial dysfunction after DES
implantation is not primarily caused by the durability of the polymer coating.
PMID- 26440471
TI - The safety and efficacy of ledipasvir/sofosbuvir for the treatment of a
nosocomial outbreak of HCV in patients with significant cardiovascular disease.
AB - BACKGROUND: There is an unmet need for interferon- and ribavirin-free treatment
for chronic HCV infection in patients with comorbidities including cardiovascular
disease (CVD). The aim of this study was to evaluate the rates of sustained
virological response (SVR) and adverse events in a cohort of patients with
nosocomially acquired HCV genotype-1b following 12 weeks of therapy with fixed
dose combination (FDC) ledipasvir/sofosbuvir (LDV/SOF). METHODS: This is a
prospective, single-centre, open-label study of five non-cirrhotic patients with
HCV genotype-1b and significant comorbid CVD, conducted at the Massachusetts
General Hospital. All patients were prescribed an FDC tablet (LDV 90 mg/SOF 400
mg) once daily for 12 weeks. Serial measurements of safety parameters, virology,
host immune correlates and adherence were performed. The primary outcome was the
proportion of patients with SVR (plasma HCV RNA level <25 IU/ml), 12 weeks after
treatment completion (SVR12). RESULTS: All five patients (100%) achieved SVR12,
with no episodes of on- or post-treatment relapse. The most commonly reported
adverse events were gastrointestinal illness and upper respiratory viral-type
illness. There were no serious adverse events or discontinuations of medication
attributable to the study drug. Deep sequencing analysis revealed no baseline
NS3, NS5A or NS5B resistance-associated variants. CONCLUSIONS: In this open
label, uncontrolled, pilot study enrolling patients with HCV genotype-1b and
significant CVD, administration of a fixed-dose, oral combination of LDV and SOF
for 12 weeks was associated with high rates of SVR and minimal adverse events.
Larger prospective studies that also include patients with cirrhosis and prior
treatment non-responders are necessary.
PMID- 26440472
TI - Childhood obesity as a predictor of morbidity in adulthood: a systematic review
and meta-analysis.
AB - Obese children are at higher risk of being obese as adults, and adult obesity is
associated with an increased risk of morbidity. This systematic review and meta
analysis investigates the ability of childhood body mass index (BMI) to predict
obesity-related morbidities in adulthood. Thirty-seven studies were included.
High childhood BMI was associated with an increased incidence of adult diabetes
(OR 1.70; 95% CI 1.30-2.22), coronary heart disease (CHD) (OR 1.20; 95% CI 1.10
1.31) and a range of cancers, but not stroke or breast cancer. The accuracy of
childhood BMI when predicting any adult morbidity was low. Only 31% of future
diabetes and 22% of future hypertension and CHD occurred in children aged 12 or
over classified as being overweight or obese. Only 20% of all adult cancers
occurred in children classified as being overweight or obese. Childhood obesity
is associated with moderately increased risks of adult obesity-related morbidity,
but the increase in risk is not large enough for childhood BMI to be a good
predictor of the incidence of adult morbidities. This is because the majority of
adult obesity-related morbidity occurs in adults who were of healthy weight in
childhood. Therefore, targeting obesity reduction solely at obese or overweight
children may not substantially reduce the overall burden of obesity-related
disease in adulthood.
PMID- 26440473
TI - Abeta-42 lowering agents from the marine-derived fungus Dichotomomyces cejpii.
AB - The ascomycete Dichotomomyces cejpii was isolated from the marine sponge
Callyspongia cf. C. flammea. Three new steroids (1-3), two of which are present
as glycosides, with an untypical pattern of carbon-carbon double bounds, were
obtained from fungal extracts, as well as the known xanthocillin X dimethyl ether
(4). Compounds 2 and 4 were evaluated in an Alzheimer's disease cellular assay
and found capable of preventing the enhanced production of amyloid beta-42 in
Aftin-5 treated cells. Abeta-42 lowering agents are considered as candidates for
the treatment of neurodegenerative Alzheimer's disease.
PMID- 26440474
TI - A simple and affordable membrane-feeding method for Aedes aegpyti and Anopheles
minimus (Diptera: Culicidae).
AB - This study developed an artificial feeding (AF) method to replace direct host
feeding (DHF) for the maintenance of Aedes aegypti and Anopheles minimus mosquito
colonies. The procedure can be adopted by all laboratories due to its simple and
affordable materials and design. The apparatus consists of heparinized cow blood
contained in a 5cm diameter glass petri dish with 5cm(2) Parafilm M (Bemis((r)))
stretched thinly over the top, with a pre-heated bag of vegetable oil placed
underneath to keep the blood warm. Both parts are contained within an insulated
StyrofoamTM box with a hole in the lid for mosquitoes to access the membrane.
Mosquitoes are fed by AF for 15min at a time. Feeding rate and fecundity of Ae.
aegypti mosquitoes feeding on the AF device were compared to those feeding on a
live rat (DHF(r)), and of Anopheles minimus mosquitoes feeding on the AF device
compared to those feeding on a human arm (DHF(h)). Aedes aegypti mosquitoes fed
by AF or DHF(r) had similar feeding rates (38.2+/-21.5% and 35.7+/-18.2%,
respectively) and overall egg production (1.5% difference). Anopheles minimus
mosquitoes fed by the AF method had a lower feeding rate (52.0+/-1.0% for AF
compared to 70.7+/-20.2% for DHF(h)) and overall egg production (40% reduction
compared to DHF(h)). However, the number of eggs produced by AF-fed mosquitoes
(1808 eggs per 100 mosquitoes) was still sufficient for colony maintenance, and
with increased feeding time both parameters are expected to increase. Reduced
feeding rate and overall egg production was observed when Ae. aegypti mosquitoes
were fed on blood refrigerated for over two weeks. In conclusion, an AF device
has been developed which can replace DHF for Ae. aegypti and An. minimus colony
maintenance when using blood refrigerated for a maximum of two weeks.
PMID- 26440475
TI - Factors Affecting Early Services for Children Who Are Hard of Hearing.
AB - PURPOSE: To describe factors affecting early intervention (EI) for children who
are hard of hearing, we analyzed (a) service setting(s) and the relationship of
setting to families' frequency of participation, and (b) provider preparation,
caseload composition, and experience in relation to comfort with skills that
support spoken language for children who are deaf and hard of hearing (CDHH).
METHOD: Participants included 122 EI professionals who completed an online
questionnaire annually and 131 parents who participated in annual telephone
interviews. RESULTS: Most families received EI in the home. Family participation
in this setting was significantly higher than in services provided elsewhere. EI
professionals were primarily teachers of CDHH or speech-language pathologists.
Caseload composition was correlated moderately to strongly with most provider
comfort levels. Level of preparation to support spoken language weakly to
moderately correlated with provider comfort with 18 specific skills. CONCLUSIONS:
Results suggest family involvement is highest when EI is home-based, which
supports the need for EI in the home whenever possible. Access to hands-on
experience with this population, reflected in a high percentage of CDHH on
providers' current caseloads, contributed to professional comfort. Specialized
preparation made a modest contribution to comfort level.
PMID- 26440476
TI - Shortcomings of prosthodontic rehabilitation of patients living in long-term care
facilities.
AB - Removable dentures are a non-invasive, cost-effective prosthodontic solution for
the reduced dentition. Their intended purpose is the rehabilitation of harmonious
oral function and aesthetics on a long-term basis. The prevalence of removable
dentures among patients of advanced age is high and the quality of the dentures
is often poor. The aim of this study was to find the most important shortcomings
of removable dentures and address the main targets for improving the quality of
prosthodontic rehabilitation. The records from dental check-ups in Austrian
residential homes were analysed retrospectively. Dental anamnesis questionnaires
and data from the clinical examinations of 105 denture wearers were analysed. The
functional condition and retention of 192 dentures had been assessed, as well as
the impact of the dentures on the intra-oral tissues. Insufficient denture
retention was very common, particularly in the lower jaw (56.0%). Problems with
the masticatory function were reported by 26.7% of the denture wearers, 11.4%
were dissatisfied with the denture aesthetics, and 4.8% had difficulties with
phonetics. Traumatic ulcers were found in 18.1%. Cracks, broken pieces (6.3%) or
missing denture teeth (2.1%) were rare. It may be assumed that the findings of
the present study also apply to a great percentage of community-dwelling seniors.
The most important issues in prosthodontic rehabilitation with removable dentures
are denture retention and masticatory function. Regular dental check-ups, denture
adjustment and, when necessary, relining can maintain the primary denture quality
and prevent damages of the oral tissues caused by ill-fitting dentures.
PMID- 26440477
TI - Effect of Selenium Deficiency on Nitric Oxide and Heat Shock Proteins in Chicken
Erythrocytes.
AB - Selenium (Se) deficiency induces various types of diseases, including hemolytic
anemia, which is one of the basic pathologies of erythrocyte damage. To
investigate the effect of Se deficiency on chicken erythrocytes, we detected the
effects of Se deficiency on the nitric oxide (NO) content and the levels of heat
shock proteins (Hsps) in chicken erythrocytes, including Hsp27, Hsp40, Hsp60,
Hsp70, and Hsp90. One-day-old chickens (180) were randomly divided into two
groups, a low-Se group (L group, fed with a 0.008 mg/kg Se diet) and a control
group (C group, fed with a 0.2 mg/kg Se diet). Next, erythrocytes were collected
at 35 days old, and the NO content, activity of inducible nitric oxide synthase
(iNOS), and levels of Hsps (27, 40, 60, 70, and 90) were examined. Compared with
the C group, the NO and iNOS levels were significantly higher (P < 0.05), and the
Hsps in the mRNA and protein levels were generally higher (P < 0.05) in the L
group. Meanwhile, the correlation analysis showed that there were positive
correlations between Hsps and NO. Thus, as typical damage biomarkers, NO and Hsps
may play special roles in chicken erythrocyte injury by Se deficiency.
PMID- 26440478
TI - Nickel Chloride (NiCl2) Induces Histopathological Lesions via Oxidative Damage in
the Broiler's Bursa of Fabricius.
AB - The purpose of this study was to investigate the histopathological lesions,
oxidative damage, changes of immunoglobulin G (IgG), immunoglobulin M (IgM), and
immunoglobulin A (IgA) contents in the bursa of Fabricius and serum
immunoglobulins (IgG, IgM, IgA) induced by dietary nickel chloride (NiCl2). Two
hundred and eighty-one-day-old broilers were randomly divided into four groups
and fed on a control diet and three experimental diets supplemented with 300,
600, and 900 mg/kg of NiCl2 for 42 days. Lesions were observed in the NiCl2
treated groups. Histopathologically, lymphocytes were decreased in lymphoid
follicles with thinner cortices and wider medullae. Concurrently, the activities
of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px),
and the ability to inhibit hydroxyl radical and glutathione (GSH) contents were
significantly (p < 0.05 or p < 0.01) decreased, while malondialdehyde (MDA)
contents were increased in the NiCl2-treated groups. The serum IgG, IgM, and
bursa IgG and IgM contents were significantly (p < 0.05 or p < 0.01) lower in the
NiCl2-treated groups than those in the control group. The above-mentioned results
show that dietary NiCl2 in excess of 300 mg/kg can cause histopathological
lesions via oxidative damage, which finally impairs the function of the bursa of
Fabricius and reduces IgG and IgM contents of the serum and the bursa of
Fabricius. The study is aimed to provide helpful materials for studies on Ni- or
Ni compounds-induced B cell toxicity in both human and other animals in the
future.
PMID- 26440479
TI - Functionalized Carbon Quantum Dots with Dopamine for Tyrosinase Activity
Monitoring and Inhibitor Screening: In Vitro and Intracellular Investigation.
AB - Sensitive assay of tyrosinase (TYR) activity is in urgent demand for both
fundamental research and practical application, but the exploration of functional
materials with good biocompatibility for its activity evaluation at the
intracellular level is still challenging until now. In this work, we develop a
convenient and real-time assay with high sensitivity for TYR activity/level
monitoring and its inhibitor screening based on biocompatible dopamine
functionalized carbon quantum dots (Dopa-CQDs). Dopamine with redox property was
functionalized on the surface of carbon quantum dots to construct a Dopa-CQDs
conjugate with strong bluish green fluorescence. When the dopamine moiety in Dopa
CQDs conjugate was oxidized to a dopaquinone derivative under specific catalysis
of TYR, an intraparticle photoinduced electron transfer (PET) process between
CQDs and dopaquinone moiety took place, and then the fluorescence of the
conjugate could be quenched simultaneously. Quantitative evaluation of TYR
activity was established in terms of the relationship between fluorescence
quenching efficiency and TYR activity. The assay covered a broad linear range of
up to 800 U/L with a low detection limit of 7.0 U/L. Arbutin, a typical inhibitor
of TYR, was chosen as an example to assess its function of inhibitor screening,
and positive results were observed that fluorescence quenching extent of the
probe was reduced in the presence of arbutin. It is also demonstrated that Dopa
CQD conjugate possesses excellent biocompatibility, and can sensitively monitor
intracellular tyrosinase level in melanoma cells and intracellular pH changes in
living cells, which provides great potential in application of TYR/pH-associated
disease monitoring and medical diagnostics.
PMID- 26440480
TI - LDA-Mediated Synthesis of Triarylmethanes by Arylation of Diarylmethanes with
Fluoroarenes at Room Temperature.
AB - A practical and convenient approach for the secondary C(sp(3))-H arylation of
diarylmethanes with various fluoroarenes is described. The reaction proceeds
smoothly in the presence of LDA (lithium diisopropylamide) at room temperature
and affords triarylmethanes in moderate to high yields.
PMID- 26440481
TI - Evaluating the impact of accreditation and external peer review.
AB - PURPOSE: Accreditation and external peer review play important roles in assessing
and improving healthcare quality worldwide. Evidence on the impact on the quality
of care remains indecisive because of programme features and methodological
research challenges. The purpose of this paper is to create a general
methodological research framework to design future studies in this field.
DESIGN/METHODOLOGY/APPROACH: A literature search on effects of external peer
review and accreditation was conducted using PubMed/Medline, Embase and Web of
Science. Three researchers independently screened the studies. Only original
research papers that studied the impact on the quality of care were included.
Studies were evaluated by their objectives and outcomes, study size and analysis
entity (hospitals vs patients), theoretical framework, focus of the studied
programme, heterogeneity of the study population and presence of a control group.
FINDINGS: After careful selection 50 articles were included out of an initial
2,025 retrieved references. Analysis showed a wide variation in methodological
characteristics. Most studies are performed cross-sectionally and results are not
linked to the programme by a theoretical framework. ORIGINALITY/VALUE: Based on
the methodological characteristics of previous studies the authors propose a
general research framework. This framework is intended to support the design of
future research to evaluate the effects of accreditation and external peer review
on the quality of care.
PMID- 26440482
TI - Service quality of hospital outpatient departments: patients' perspective.
AB - PURPOSE: Assessment of patient perceptions of health service quality as an
important element in quality assessments has attracted much attention in recent
years. The purpose of this paper is to assess the service quality of hospital
outpatient departments affiliated to Shahid Beheshti University of Medical
Sciences from the patients' perspective. DESIGN/METHODOLOGY/APPROACH: This cross
sectional study was conducted in 2014 in Tehran, Iran. The study samples included
500 patients who were selected by multi-stage random sampling from four
hospitals. The data collection instrument was a questionnaire consisting of 50
items, and the validity and reliability of the questionnaire were confirmed. For
data analysis, exploratory and confirmatory factor analysis, Friedman test, and
descriptive statistics were used through LISREL 8.54 and SPSS 18 applications.
FINDINGS: Eight significant factors were extracted for outpatient service
quality, which explained about 67 per cent of the total variance. Physician
consultation, information provided to the patient, and the physical environment
of the clinic were the three determining factors of the quality of outpatient
services. The highest and lowest perceptions were related to physician
consultation and perceived waiting time dimension, respectively. The mean score
of patients' perception of outpatient service quality was 3.89 (+/-0.60). About
59.5 per cent of patients assessed the quality of outpatient services as good,
38.2 per cent as moderate, and 2.3 per cent as poor. Practical implications - The
instrument developed for this study is valid and reliable, and it can help
hospital managers to identify the areas needing improvement and correction.
ORIGINALITY/VALUE: According to the findings of this study, the majority of
patients had a positive experience with outpatient departments of teaching
hospitals, and the services provided in these centres were of adequate quality,
based on patient assessments.
PMID- 26440483
TI - Investigating the connections between health lean management and clinical risk
management.
AB - PURPOSE: The purpose of this paper is to investigate connections and overlaps
between health lean management (HLM) and clinical risk management (CRM)
understanding whether and how these two approaches can be combined together to
pursue efficiency and patient safety improvements simultaneously.
DESIGN/METHODOLOGY/APPROACH: A systematic literature review has been carried out.
Searching in academic databases, papers that focus not only on HLM, but also on
clinical errors and risk reduction, were included. The general characteristics of
the selected papers were analysed and a content analysis was conducted. FINDINGS:
In most of the papers, pursing objectives of HLM and CRM and adopting tools and
practices of both approaches, results of quality and, particularly, of safety
improvements were obtained. A two-way arrow between HLM and CRM emerged but so
far, none of the studies has been focused on the relationship between HLM and
CRM. ORIGINALITY/VALUE: Results highlight an emerging research stream, with many
useful theoretical and practical implications and opportunities for further
research.
PMID- 26440484
TI - Comparing Choice and Partnership Approach assumptions to Child and Adolescent
Mental Health Services in NHS Greater Glasgow and Clyde.
AB - PURPOSE: The purpose of this paper is to compare NHS Greater Glasgow and Clyde
(NHSGGC) Child and Adolescent Mental Health Service (CAMHS) activity data over a
one-year period to the Choice and Partnership Approach (CAPA) demand and capacity
model assumptions, providing an evaluation of CAPA model implementation and its
effects on actual demand and capacity of the service.
DESIGN/METHODOLOGY/APPROACH: Three assumptions within the CAPA model are tested
against activity data extracted from the patient management system. Analysis by
patient record assesses the number of appointments the patients received and the
patients' journey from assessment to treatment. A combination of community CAMHS
data are combined to compare actual activity against assumed capacity required to
meet demand according to the CAPA model. FINDINGS: Tested against an audit of
2,896 patient records, CAMHS average 7.76 core appointments per patient compared
to the CAPA assumption of 7.5 appointments at a 0 per cent DNA rate. The second
CAPA assumption states that 66 per cent of assessments will result in treatment,
compared to 73.55 per cent in NHSGGC CAMHS. Finally, the workforce model in CAMHS
has clinical capacity to meet demand according to the CAPA assumption of weekly
accepted referral rates not exceeding the number of clinical whole time
equivalent. ORIGINALITY/VALUE: The data allow for identification of
inefficiencies within CAMHS and highlights how capacity can be increased, without
increasing budgets, to meet a rising clinical demand. The results allow managers
and clinicians to improve job planning to ensure more children and young people
have quick access to services.
PMID- 26440485
TI - Applying importance-performance analysis to patient safety culture.
AB - PURPOSE: The Sexton et al.'s (2006) safety attitudes questionnaire (SAQ) has been
widely used to assess staff's attitudes towards patient safety in healthcare
organizations. However, to date there have been few studies that discuss the
perceptions of patient safety both from hospital staff and upper management. The
purpose of this paper is to improve and to develop better strategies regarding
patient safety in healthcare organizations. DESIGN/METHODOLOGY/APPROACH: The
Chinese version of SAQ based on the Taiwan Joint Commission on Hospital
Accreditation is used to evaluate the perceptions of hospital staff. The current
study then lies in applying importance-performance analysis technique to identify
the major strengths and weaknesses of the safety culture. FINDINGS: The results
show that teamwork climate, safety climate, job satisfaction, stress recognition
and working conditions are major strengths and should be maintained in order to
provide a better patient safety culture. On the contrary, perceptions of
management and hospital handoffs and transitions are important weaknesses and
should be improved immediately. Research limitations/implications - The research
is restricted in generalizability. The assessment of hospital staff in patient
safety culture is physicians and registered nurses. It would be interesting to
further evaluate other staff's (e.g. technicians, pharmacists and others)
opinions regarding patient safety culture in the hospital. ORIGINALITY/VALUE: Few
studies have clearly evaluated the perceptions of healthcare organization
management regarding patient safety culture. Healthcare managers enable to take
more effective actions to improve the level of patient safety by investigating
key characteristics (either strengths or weaknesses) that healthcare
organizations should focus on.
PMID- 26440486
TI - Patient satisfaction constructs.
AB - PURPOSE: The purpose of this paper is to examine the five-factor structure of
patients' satisfaction constructs toward private healthcare service providers.
DESIGN/METHODOLOGY/APPROACH: This research is a cross-sectional study. A
questionnaire-based survey was conducted with previous and current Bangladeshi
patients. Exploratory factor analysis was employed to extract the underlying
constructs. FINDINGS: Five underlying dimensions that play a significant role in
structuring the satisfaction perceived by Bangladeshi private healthcare patients
are identified in this study. Practical implications - The main contribution of
this study is identifying the dimensions of satisfaction perceived by Bangladeshi
patients regarding private healthcare service providers. ORIGINALITY/VALUE:
Healthcare managers adopt the five identified underlying construct items in their
business practices to improve their respective healthcare efficiency while
ensuring overall customer satisfaction.
PMID- 26440487
TI - Lean Six Sigma implementation and organizational culture.
AB - PURPOSE: The purpose of this paper is to examine the relationship between four
organizational cultural types defined by the Competing Values Framework and three
Lean Six Sigma implementation components - management involvement, use of Lean
Six Sigma methods and Lean Six Sigma infrastructure. DESIGN/METHODOLOGY/APPROACH:
The study involved surveying 446 human resource and quality managers from 223
hospitals located in Maine, New Hampshire, Vermont, Massachusetts and Rhode
Island using the Organizational Culture Assessment Instrument. Findings - In
total, 104 completed responses were received and analyzed using multivariate
analysis of variance. Follow-up analysis of variances showed management support
was significant, F(3, 100)=4.89, p < 0.01, eta2=1.28; infrastructure was not
significant, F(3, 100)=1.55, p=0.21, eta2=0.05; and using Lean Six Sigma methods
was also not significant, F(3, 100)=1.34, p=0.26, eta2=0.04. Post hoc analysis
identified group and development cultures having significant interactions with
management support. PRACTICAL IMPLICATIONS: The relationship between
organizational culture and Lean Six Sigma in hospitals provides information on
how specific cultural characteristics impact the Lean Six Sigma initiative key
components. This information assists hospital staff who are considering
implementing quality initiatives by providing an understanding of what cultural
values correspond to effective Lean Six Sigma implementation. ORIGINALITY/VALUE:
Managers understanding the quality initiative cultural underpinnings, are
attentive to the culture-shared values and norm's influence can utilize
strategies to better implement Lean Six Sigma.
PMID- 26440488
TI - Do clinical incidents, complaints and medicolegal claims overlap?
AB - PURPOSE: Error reporting by healthcare staff, patient-derived complaints and
patient-derived medico-legal claims are three separate processes present in most
healthcare systems. It is generally assumed that all relate to the same cases.
Given the high costs associated with these processes and strong desire to
maximise quality and standards, the purpose of this paper is to see whether it
was indeed the case that most complaints and claims related to medical errors and
the relative resource allocation to each group. DESIGN/METHODOLOGY/APPROACH:
Electronic databases for clinical error recording, patient complaints and medico
legal claims in a large NHS healthcare provider organisation were reviewed and
case overlap analysed. FINDINGS: Most complaints and medico-legal claims do not
associate with a prior clinical error. Disproportionate resource is required for
a small number of complaints and the medico-legal claims process. Most complaints
and claims are not upheld. RESEARCH LIMITATIONS/IMPLICATIONS: The authors have
only looked at data from one healthcare provider and for one period. It would be
useful to analyse other healthcare organisations over a longer time period. The
authors were unable to access data on secondary staffing costs, which would have
been informative. As the medico-legal process can go on for many years, the
authors do not know the ultimate outcomes for all cases. The authors also do not
know how many medico-legal cases were settled out of court pragmatically to
minimise costs. Practical implications - Staff error reporting systems and
patient advisory services seem to be efficient and working well. However, the
broader complaints and claims process is costing considerable time and money, yet
may not be useful in driving up standards. System changes to maximise helpful
complaints and claims, from a quality and standards perspective, and minimise
unhelpful ones are recommended. ORIGINALITY/VALUE: This study provides important
data on the lack of overlap between errors, complaints and claims cases.
PMID- 26440489
TI - Early warning scores: unravelling detection and escalation.
AB - PURPOSE: The purpose of this paper is to increase understanding of how patient
deterioration is detected and how clinical care escalates when early warning
score (EWS) systems are used. DESIGN/METHODOLOGY/APPROACH: The authors critically
review a recent National Early Warning Score paper published in IJHCQA using
personal experience and EWS-related publications, and debate the difference
between detection and escalation. FINDINGS: Incorrect EWS choice or poorly
understood EWS escalation may result in unnecessary workloads forward and
responding staff. PRACTICAL IMPLICATIONS: EWS system implementers may need to
revisit their guidance materials; medical and nurse educators may need to expand
the curriculum to improve EWS system understanding and use. ORIGINALITY/VALUE:
The paper raises the EWS debate and alerts EWS users that scrutiny is required.
PMID- 26440490
TI - External Validation of the STONE Score, a Clinical Prediction Rule for Ureteral
Stone: An Observational Multi-institutional Study.
AB - STUDY OBJECTIVE: The STONE score is a clinical decision rule that classifies
patients with suspected nephrolithiasis into low-, moderate-, and high-score
groups, with corresponding probabilities of ureteral stone. We evaluate the STONE
score in a multi-institutional cohort compared with physician gestalt and
hypothesize that it has a sufficiently high specificity to allow clinicians to
defer computed tomography (CT) scan in patients with suspected nephrolithiasis.
METHODS: We assessed the STONE score with data from a randomized trial for
participants with suspected nephrolithiasis who enrolled at 9 emergency
departments between October 2011 and February 2013. In accordance with STONE
predictors, we categorized participants into low-, moderate-, or high-score
groups. We determined the performance of the STONE score and physician gestalt
for ureteral stone. RESULTS: Eight hundred forty-five participants were included
for analysis; 331 (39%) had a ureteral stone. The global performance of the STONE
score was superior to physician gestalt (area under the receiver operating
characteristic curve=0.78 [95% confidence interval {CI} 0.74 to 0.81] versus 0.68
[95% CI 0.64 to 0.71]). The prevalence of ureteral stone on CT scan ranged from
14% (95% CI 9% to 19%) to 73% (95% CI 67% to 78%) in the low-, moderate-, and
high-score groups. The sensitivity and specificity of a high score were 53% (95%
CI 48% to 59%) and 87% (95% CI 84% to 90%), respectively. CONCLUSION: The STONE
score can successfully aggregate patients into low-, medium-, and high-risk
groups and predicts ureteral stone with a higher specificity than physician
gestalt. However, in its present form, the STONE score lacks sufficient accuracy
to allow clinicians to defer CT scan for suspected ureteral stone.
PMID- 26440492
TI - Are New Oral Anticoagulants Safer Than Vitamin K Antagonists in the Treatment of
Venous Thromboembolism?
PMID- 26440491
TI - A Case of Acute Upper Airway Obstruction in a Pediatric Hemophilia A Patient
Because of Spontaneous Retropharyngeal Hemorrhage.
AB - We report a rare case of acute upper airway obstruction caused by spontaneous
retropharyngeal hemorrhage as a result of hemophilia A in a 16-year-old pediatric
patient who routinely received factor VIII replacement. Initial diagnosis was
delayed because the patient presented with symptoms, such as throat pain and
odynophagia, similar to those of common benign upper airway infections. Within 2
days of the initial presentation of symptoms, the patient went into respiratory
failure as a result of retropharyngeal hemorrhage. The possibility of spontaneous
retropharyngeal or epiglottic hemorrhage or hematoma should be considered as a
cause of rapidly progressing odynophagia and dyspnea by hemophilia patients.
PMID- 26440493
TI - A Universal Animal Welfare Framework for Zoos.
AB - The Detroit Zoological Society's (DZS) Center for Zoo Animal Welfare (CZAW) was
created to advance the science and policy of the welfare of exotic nonhuman
animals in captivity. This important part of the DZS mission is achieved through
assessments of, and research on, the welfare of animals in zoos; by recognizing
extraordinary achievement in the advancement of animal welfare; by widely sharing
knowledge through a bibliographic resource center; by conducting professional
training for animal care staff; and by convening important discussions in the
form of international symposia. This special issue of the Journal of Applied
Animal Welfare Science features selected papers from the most recent
international CZAW symposium held at the Detroit Zoo in November 2014, as well as
a universal framework for zoo animal welfare developed by the DZS.
PMID- 26440494
TI - Bird-Window Collisions: A Critical Animal Welfare and Conservation Issue.
AB - Sheet glass and plastic in the form of clear and reflective windows are
universally lethal to birds. Reasonable interpretation of available scientific
evidence describes windows as a principal human-associated avian mortality factor
that is an indiscriminant killer of common species as well as species of
conservation concern. A conservative toll estimates 1 billion or more annual
fatalities in the United States alone. The injury and death from birds striking
windows are foreseeable and preventable, but the most promising legal measures
and commercial products are not being applied or made available to protect
defenseless victims. Avian window casualties are important for birds and people,
and they have nonhuman animal welfare, biodiversity, sustainability, legal, and
ethical and moral value justifying responsible human action. Preventing this
unintended and unwanted lethal hazard for free-flying birds should be an
obligation. Short-term solutions include retrofitting existing panes with a
variety of proven measures that among others include applying various materials
to cover the outside surface of windows. Long-term solutions include current and
proposed bird-safe sheet glass and plastic for remodeling and new construction
that have patterns that transform windows into barriers that birds see and avoid.
PMID- 26440495
TI - A "How-To" Guide for Designing Judgment Bias Studies to Assess Captive Animal
Welfare.
AB - Robust methods to assess nonhuman animal emotion are essential for ensuring good
welfare in captivity. Cognitive bias measures such as the judgment bias task have
recently emerged as promising tools to assess animal emotion. The simple design
and objective response measures make judgment bias tasks suitable for use across
species and contexts. In reviewing 64 studies published to date, it emerged that
(a) judgment biases have been measured in a number of mammals and birds and an
invertebrate; (b) no study has tested judgment bias in any species of fish,
amphibian, or reptile; and (c) no study has yet investigated judgment bias in a
zoo or aquarium. This article proposes that judgment bias measures are highly
suitable for use with these understudied taxa and can provide new insight into
welfare in endangered species housed in zoos and aquariums, where poor welfare
impacts breeding success and, ultimately, species survival. The article includes
a "how-to" guide to designing judgment bias tests with recommendations for
working with currently neglected "exotics" including fishes, amphibians, and
reptiles.
PMID- 26440496
TI - A Multi-Institutional Assessment of Factors Influencing Locomotion and Pacing in
Captive Okapis (Okapia johnstoni).
AB - The okapi (Okapia johnstoni), native to the Democratic Republic of Congo, is a
large, solitary, and diurnal forest-dwelling ungulate highly sensitive to captive
conditions. The captive population demonstrates persistent health problems,
reproductive abnormalities, and several potentially abnormal repetitive
behaviors. This study reports on locomotion and pacing in adult male and female
okapis. Commonly, data on repetitive behavior have been derived from surveys.
Although insightful, the results are often highly generalized and provide little
information about the true preponderance and nature of such behavior in a
population. In this study, direct observations determining how often and when a
behavior of interest occurs are paired with information on factors (intrinsic and
extrinsic) that can impact a nonhuman animal's propensity to perform repetitive
behavior. More than half of the North American okapi population comprised the
study population. Each animal was studied for 2 summer and winter seasons.
Factors predictive of pacing in both males and females included 3 housing and
habitat factors and 4 management factors. Patterns of locomotion and the rate and
pattern of pacing in males when compared with females suggested different
mechanisms may be driving these behaviors in the different sexes and that a sex
specific management strategy would benefit this species.
PMID- 26440498
TI - Resistance to water and abrasion of a broad-spectrum sunscreen: a prospective,
open-label study.
PMID- 26440500
TI - Advancing Pharmacogenomics as a Component of Precision Medicine: How, Where, and
Who?
AB - Pharmacogenomics is an important element of precision medicine. Advances in
pharmacogenomics implementation have been made but significant barriers remain,
including evidence, reimbursement, and clinician knowledge, among others.
Widespread adoption of pharmacogenomics requires overcoming these barriers, a
clinician champion group, which we propose will be pharmacists, and an easily
accessible setting, which may be the community pharmacy. Whatever the path, it
must be evidence-driven and pharmacogenomics must improve drug-related outcomes
to become a standard of care.
PMID- 26440501
TI - Applied research of an emerging condition: Theileria associated bovine anaemia.
PMID- 26440502
TI - Karyotype characterization and evolution in South American species of Lathyrus
(Notolathyrus, Leguminosae) evidenced by heterochromatin and rDNA mapping.
AB - Notolathyrus is a section of South American endemic species of the genus
Lathyrus. The origin, phylogenetic relationship and delimitation of some species
are still controversial. The present study provides an exhaustive analysis of the
karyotypes of approximately half (10) of the species recognized for section
Notolathyrus and four outgroups (sections Lathyrus and Orobus) by cytogenetic
mapping of heterochromatic bands and 45S and 5S rDNA loci. The bulk of the
parameters analyzed here generated markers to identify most of the chromosomes in
the complements of the analyzed species. Chromosome banding showed interspecific
variation in the amount and distribution of heterochromatin, and together with
the distribution of rDNA loci, allowed the characterization of all the species
studied here. Additionally, some of the chromosome parameters described (st
chromosomes and the 45S rDNA loci) constitute the first diagnostic characters for
the Notolathyrus section. Evolutionary, chromosome data revealed that the South
American species are a homogeneous group supporting the monophyly of the section.
Variation in the amount of heterochromatin was not directly related to the
variation in DNA content of the Notolathyrus species. However, the correlation
observed between the amount of heterochromatin and some geographical and
bioclimatic variables suggest that the variation in the heterochromatic fraction
should have an adaptive value.
PMID- 26440504
TI - A Nanoparticle-based Sensor Platform for Cell Tracking and Status/Function
Assessment.
AB - Nanoparticles are increasingly popular choices for labeling and tracking cells in
biomedical applications such as cell therapy. However, all current types of
nanoparticles fail to provide real-time, noninvasive monitoring of cell status
and functions while often generating false positive signals. Herein, a nanosensor
platform to track the real-time expression of specific biomarkers that correlate
with cell status and functions is reported. Nanosensors are synthesized by
encapsulating various sensor molecules within biodegradable polymeric
nanoparticles. Upon intracellular entry, nanosensors reside within the cell
cytoplasm, serving as a depot to continuously release sensor molecules for up to
30 days. In the absence of the target biomarkers, the released sensor molecules
remain 'Off'. When the biomarker(s) is expressed, a detectable signal is
generated (On). As a proof-of-concept, three nanosensor formulations were
synthesized to monitor cell viability, secretion of nitric oxide, and beta-actin
mRNA expression.
PMID- 26440503
TI - The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase
Regulate Extracellular Matrix Organization and BMP Signaling in the Developing
Wing of Drosophila melanogaster.
AB - The developing crossveins of the wing of Drosophila melanogaster are specified by
long-range BMP signaling and are especially sensitive to loss of extracellular
modulators of BMP signaling such as the Chordin homolog Short gastrulation (Sog).
However, the role of the extracellular matrix in BMP signaling and Sog activity
in the crossveins has been poorly explored. Using a genetic mosaic screen for
mutations that disrupt BMP signaling and posterior crossvein development, we
identify Gyc76C, a member of the receptor guanylyl cyclase family that includes
mammalian natriuretic peptide receptors. We show that Gyc76C and the soluble cGMP
dependent kinase Foraging, likely linked by cGMP, are necessary for normal
refinement and maintenance of long-range BMP signaling in the posterior
crossvein. This does not occur through cell-autonomous crosstalk between cGMP and
BMP signal transduction, but likely through altered extracellular activity of
Sog. We identify a novel pathway leading from Gyc76C to the organization of the
wing extracellular matrix by matrix metalloproteinases, and show that both the
extracellular matrix and BMP signaling effects are largely mediated by changes in
the activity of matrix metalloproteinases. We discuss parallels and differences
between this pathway and other examples of cGMP activity in both Drosophila
melanogaster and mammalian cells and tissues.
PMID- 26440505
TI - Sex differences in fatigability of dynamic contractions.
AB - NEW FINDINGS: What is the topic of this review? Women are usually less fatigable
than men for isometric fatiguing contractions of similar intensity, but whether
this occurs for dynamic tasks is less clear. This review presents evidence that
the sex difference in muscle fatigue of repeated dynamic contractions is specific
to the task requirements, including the velocity of shortening and the muscle
group involved. What advances does it highlight? Contractile mechanisms are
responsible for the sex differences in muscle fatigue for slow-velocity and low
load dynamic tasks. The variability of the sex difference in fatigability among
dynamic tasks has implications for fatiguing contractions prescribed in training
and rehabilitation to men and women. Women are usually less fatigable than men
during single-limb isometric contractions, primarily because of sex-related
differences in contractile mechanisms. It is less clear whether these sex
differences in muscle fatigue occur for dynamic fatiguing tasks. This review
highlights new findings that the sex difference in fatigability for dynamic
shortening contractions with a single limb is dependent on the contraction
velocity and the muscle group involved. Recent studies demonstrate that women are
less fatigable than men for a dynamic task as follows: (i) the elbow-flexor
muscles at slow- but not high-velocity contractions; and (ii) the knee-extensor
muscles when muscle fatigue was quantified as a reduction in the maximal
voluntary isometric contraction force after the dynamic fatiguing task.
Contractile mechanisms are responsible for the sex difference in muscle fatigue
of the dynamic contractions, with no evidence for a sex difference in the
reduction in voluntary activation (i.e. central fatigue). Thus, these findings
indicate that the sex difference in muscle fatigue of dynamic contractions is
task specific. These data also challenge the assumption that men and women
respond in a similar manner to training and rehabilitation that involve fatiguing
contractions to overload the neuromuscular system. There is, however, a
tremendous opportunity for conducting high-impact studies to gain insight into
those factors that define the sex-based differences in muscle fatigue during
dynamic tasks. Such studies can define the boundaries to human performance in
both men and women during athletic endeavours, ergonomic tasks and
rehabilitation.
PMID- 26440506
TI - Big data are coming to psychiatry: a general introduction.
AB - Big data are coming to the study of bipolar disorder and all of psychiatry. Data
are coming from providers and payers (including EMR, imaging, insurance claims
and pharmacy data), from omics (genomic, proteomic, and metabolomic data), and
from patients and non-providers (data from smart phone and Internet activities,
sensors and monitoring tools). Analysis of the big data will provide
unprecedented opportunities for exploration, descriptive observation, hypothesis
generation, and prediction, and the results of big data studies will be
incorporated into clinical practice. Technical challenges remain in the quality,
analysis and management of big data. This paper discusses some of the fundamental
opportunities and challenges of big data for psychiatry.
PMID- 26440508
TI - Takotsubo Syndrome in Patients With Spontaneous Coronary Artery Dissection:
Misdiagnosis or a Reality?
PMID- 26440507
TI - Low self-recognition and awareness of past hypomanic and manic episodes in the
general population.
AB - BACKGROUND: Bipolar disorder is often underdiagnosed and undertreated. Its
detection and correct diagnosis highly relies on the report of past hypomanic or
manic episodes. We investigated the recognition and awareness of past hypomanic
and manic episodes in a sample of respondents with bipolar disorder selected from
a general population study. METHODS: In a reappraisal study from the Netherlands
Mental Health Survey and Incidence Study (NEMESIS), we further investigated 40
respondents with lifetime bipolar disorder confirmed by the structured clinical
interview for DSM-IV (SCID). Respondents were asked about awareness of past
depressive, manic and hypomanic episodes, illness characteristics and treatment
history. RESULTS: Most respondents (82.5 %) recognized that they had experienced
a depressive episode while 75 % had consulted a health professional for a
depressive episode. Only a minority (22.5 %) recognized that they had experienced
a (hypo)manic episode and only 17.5 % had consulted a health professional for a
(hypo)manic episode. Only 12.5 % of the respondents reported having received a
diagnosis of bipolar disorder. Recognition of previous (hypo)manic episodes was
not related to severity of bipolar disorder. CONCLUSIONS: In routine clinical
practice history-taking on a syndromal level, i.e., only inquiring whether a
patient presenting with depression ever experienced a hypomanic or manic episode
or received treatment for such an episode, is not sufficient to confirm or
exclude a diagnosis of bipolar disorder. Other efforts, such as an interview with
a significant other and the use of self report questionnaires or (semi
)structured interviews may be needed to recognize previous manic symptoms in
patients with depression.
PMID- 26440509
TI - Formation and Malformation of Cardiac Trabeculae: Biological Basis, Clinical
Significance, and Special Yield of Magnetic Resonance Imaging in Assessment.
AB - Adult and pediatric cardiologists are familiar with variation in cardiac
trabeculation. Abnormal trabeculation is a key feature of left ventricular
noncompaction, but it is also common in congenital heart diseases and in
cardiomyopathies (dilated and hypertrophied). Trabeculae might be a measurable
phenotypic marker that will allow insights into how cardiomyopathy and congenital
heart disease arise and develop. This will require the linking together of
clinical and preclinical information (such as embryology and genetics), with new
analysis methods for trabecular quantitation. In adult cardiology several
promising quantitative methods have been developed for echocardiography, computed
tomography, and cardiovascular magnetic resonance, and earlier cross-sectional
caliper approaches have now been refined to permit more advanced assessment.
Adaptation of these methods for use in developmental biology might inform on
better ways to measure and track trabecular morphology in model organisms.
PMID- 26440510
TI - Reply to Letters From Madias and Y-Hassan--With Regard to "Spontaneous Coronary
Artery Dissection Misdiagnosed as Takotsubo Cardiomyopathy: A Case Series".
PMID- 26440511
TI - Standing on the Shoulders of Giants: J.A.P. Pare and the Birth of Cardiovascular
Genetics.
AB - Sudden death and stroke afflicted a family from rural Quebec with such frequency
as to be called the Coaticook curse by the local community. In Montreal in the
late 1950s, a team of physicians led by J.A.P. Pare investigated this family for
inherited cardiovascular disease. Their efforts resulted in an extensive and now
classic description of familial hypertrophic cardiomyopathy. A quarter of a
century later, the same family was the subject of linkage analysis and direct
sequencing, culminating in the isolation of a mutation in the gene encoding the
beta myosin heavy chain. MYH7 was the first gene implicated in a cardiovascular
disease, which paved the way for identification of mutations in other heritable
disorders, mechanistic studies, and clinical applications, such as predictive
testing. The present era of cardiovascular genomics arguably had its inception in
the clinical observations of Dr Pare and his colleagues more than 50 years ago.
PMID- 26440512
TI - A Systematic Review of Phenotypic Features Associated With Cardiac Troponin I
Mutations in Hereditary Cardiomyopathies.
AB - BACKGROUND: Genetic investigations have established that mutations in proteins of
the contractile unit of the myocardium, known as the sarcomere, may be associated
with hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), and
dilated cardiomyopathy (DCM). It has become clinical practice to offer genetic
testing in affected individuals to identify causative mutations, which provides
the basis for presymptomatic testing of relatives who are at risk of disease
development. This ensures adequate clinical follow-up of mutation carriers,
whereas noncarriers can be discharged. However, before genetic testing can be
used for individual risk assessment and prediction of prognosis, it is important
to investigate if there is a relation between the clinical disease expression
(phenotype) of the condition and mutations in specific disease genes (genotype).
METHODS: We reviewed the literature in relation to phenotypic features reported
to be associated with mutations in cardiac troponin I (cTnI; TNNI3), which is a
recognized sarcomeric disease gene in all 3 cardiomyopathies. RESULTS: The
results of this review did not identify specific genotype-phenotype relations in
HCM or DCM, and cTnI appeared to be the most frequent disease gene in RCM.
CONCLUSIONS: To further explore if there is a genotype-phenotype relation, long
term follow-up studies are needed. It is essential to investigate the natural
history of the condition among affected individuals and to provide clinical
follow-up on disease development among healthy mutation carriers. Such
information is required to provide evidence-based counselling for affected
families and to elucidate if knowledge about specific genotypes can be used in
future risk prediction models.
PMID- 26440513
TI - The Impact of Comprehensive Pre-visit Preparation on Patient Engagement and
Quality of Care in a Population of Underserved Patients with Diabetes: Evidence
from the Care Management Medical Home Center Model.
AB - This study evaluated the impact of pre-visit preparation, a key component of
Patient-Centered Medical Home guidelines, on compliance with recommended tests
and screenings in a diabetic patient population receiving care in Federally
Qualified Health Centers in Miami-Dade County. The pre-visit preparation
consisted of a pre-visit phone call to review patient compliance with recommended
tests and screenings, provide encouragement for self-care goal setting, answer
patient questions, assure referrals and tests were scheduled, and notify an in
center patient care team about which services are required at the upcoming visit.
Aggregated data from 7 health centers and a cohort analysis of 7491 patients
showed significantly higher compliance among those who were successfully
contacted prior to the visit compared to those who were not successfully
contacted at 24 months for all compliance measures included in the study. These
results included a 28.8 percentage point difference in compliance with HbA1c
testing, a 14.6 percentage point difference in influenza immunization, a 27.7
percentage point difference in diabetic foot exam compliance, and a 33.2
percentage point difference in compliance with annual low-density lipoprotein
testing. After 24 months, the patient no-show rate decreased by 6.8 percentage
points (from 20.7% to 14.0%) among contacted patients and by 5.5 percentage
points (from 20.7% to 15.2%) among patients who were not contacted. Study results
suggest that proactive pre-visit preparation may be a key strategy for primary
care practices to improve areas critical for chronic disease management, such as
patient engagement, appointments kept, and compliance with recommended
screenings, tests, and services. (Population Health Management 2016;19:171-177).
PMID- 26440514
TI - The importance of age and menopausal status in endometrial complex hyperplasia
with atypia.
AB - The effects of menopausal status and age on the intra-operative and post
operative pathology results of patients operated on with a pre-operative
diagnosis of complex hyperplasia with atypia (CHA) were assessed. A hundred and
eleven patients diagnosed in our centre between January 1993 and March 2013 were
included. Cancer was detected in the paraffin blocks (PBs) of 52 (46.8%)
patients. Among these, 50 patients had stage-IA disease. In 31.1% of the pre
menopausal patients and 66% of the post-menopausal patients, PB revealed cancer
(p < 0.0001). The results of frozen section (FS) and PB were concordant in 51%
and 70% in the pre-menopausal and post-menopausal patients, respectively (p =
0.041). In the patients operated on with a pre-operative diagnosis of CHA, the
probability of detecting cancer in PB increases with increasing age and
menopause. The reliability of FS is limited in younger and pre-menopausal
patients.
PMID- 26440515
TI - Low Potassium Dialysate as a Protective Factor of Sudden Cardiac Death in
Hemodialysis Patients with Hyperkalemia.
AB - AIM: Hyperkalemia increases the risk of sudden cardiac death (SCD) in
hemodialysis patients. Our objective was to determine the association between
administering low potassium dialysate to hyperkalemic hemodialysis patients and
SCD. METHODS: We conducted a retrospective cohort study with patients undergoing
maintenance hemodialysis from May 1, 2006, through December 31, 2013. The
dialysate composition was adjusted over time according to monthly laboratory
results. A 1.0 mEq/L potassium dialysate was applied in patients with predialysis
hyperkalemia (>5.5 mEq/L) and was included as a time-dependent confounding
factor. The clinical characteristics of enrolled patients, the incidence and
timing of SCD and risk factors for all-cause mortality and SCD were analyzed.
RESULTS: There were 312 patients on maintenance hemodialysis during the study
period. One hundred and fifty-seven patients had been dialyzed against a 1.0
mEq/L potassium dialysate at least once. The rates of all-cause mortality and SCD
were 48.17 and 20.74 per 1000 patient-years, respectively. A 1.12-fold increase
in the risk of SCD in the 24-hour period starting with the hemodialysis procedure
and a 1.36-fold increase in the 24 hours preceding a weekly cycle were found (p =
0.017). Multivariate Cox proportional hazards models showed that age, diabetes
mellitus and predialysis hyperkalemia (>5.0 mEq/L) were significant predictors of
all-cause mortality and SCD. Exposure to 1.0 mEq/L potassium dialysate, Kt/V, and
serum albumin were independent protective factors against all-cause mortality.
Only exposure to 1.0 mEq/L potassium dialysate significantly prevented SCD
(hazard ratio = 0.33, 95% CI = 0.13-0.85). CONCLUSIONS: Using low potassium
dialysate in hyperkalemic hemodialysis patients may prevent SCD.
PMID- 26440516
TI - Concordance of Results from Randomized and Observational Analyses within the Same
Study: A Re-Analysis of the Women's Health Initiative Limited-Access Dataset.
AB - BACKGROUND: Observational studies (OS) and randomized controlled trials (RCTs)
often report discordant results. In the Women's Health Initiative Calcium and
Vitamin D (WHI CaD) RCT, women were randomly assigned to CaD or placebo, but were
permitted to use personal calcium and vitamin D supplements, creating a unique
opportunity to compare results from randomized and observational analyses within
the same study. METHODS: WHI CaD was a 7-year RCT of 1g calcium/400IU vitamin D
daily in 36,282 post-menopausal women. We assessed the effects of CaD on
cardiovascular events, death, cancer and fracture in a randomized design-
comparing CaD with placebo in 43% of women not using personal calcium or vitamin
D supplements- and in a observational design- comparing women in the placebo
group (44%) using personal calcium and vitamin D supplements with non-users.
Incidence was assessed using Cox proportional hazards models, and results from
the two study designs deemed concordant if the absolute difference in hazard
ratios was <=0.15. We also compared results from WHI CaD to those from the WHI
Observational Study(WHI OS), which used similar methodology for analyses and
recruited from the same population. RESULTS: In WHI CaD, for myocardial
infarction and stroke, results of unadjusted and 6/8 covariate-controlled
observational analyses (age-adjusted, multivariate-adjusted, propensity-adjusted,
propensity-matched) were not concordant with the randomized design results. For
death, hip and total fracture, colorectal and total cancer, unadjusted and
covariate-controlled observational results were concordant with randomized
results. For breast cancer, unadjusted and age-adjusted observational results
were concordant with randomized results, but only 1/3 other covariate-controlled
observational results were concordant with randomized results. Multivariate
adjusted results from WHI OS were concordant with randomized WHI CaD results for
only 4/8 endpoints. CONCLUSIONS: Results of randomized analyses in WHI CaD were
concordant with observational analyses for 5/8 endpoints in WHI CaD and 4/8
endpoints in WHI OS.
PMID- 26440517
TI - Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2
Activity.
AB - Epidemiologic studies show a correlation between the dietary intake of food
polyphenols and beneficial health effects. Several in vitro studies indicate that
the anti-inflammatory potential of polyphenols is, at least in part, mediated by
a modulation of the enzymes of the arachidonic acid cascade, such as the
prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action
can be transferred to the situation in vivo is scarce. This study characterized
effects of a subset of polyphenols on COX-2 expression and activity in vitro and
compared the potency with known drugs. Next, the in vivo relevance of the
observed in vitro effects was tested. Enzyme assays and incubations of
polyphenols with the cancer cell line HCA-7 and lipopolysaccharide (LPS)
stimulated primary monocytes support the hypothesis that polyphenols can effect
COX-2 expression and activity in vitro. The effects were most pronounced in the
monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values
of 1.5 MUM, 2.6 MUM, 2.8 MUM and 7.4 MUM. However, these values are 100- to 1000
fold higher in comparison to those of the known pharmaceuticals celecoxib,
indomethacin and dexamethasone. In an animal model of LPS induced sepsis,
pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased
plasma or tissue prostaglandin levels, whereas the positive control celecoxib
effectively attenuated LPS induced prostaglandin formation. These data suggest
that despite the moderate potency in vitro, an effect of polyphenols on COX-2
during acute inflammation is unlikely, even if a high dose of polyphenols is
ingested.
PMID- 26440519
TI - [Practice relevant research in biological psychiatry].
AB - The practice of psychiatry would be unthinkable without modern
psychopharmacology. Drug treatment, especially of severe psychiatric disorders,
is often a precondition of community participation, societal reintegration and
recovery. Seen in this context it is understandable that biological psychiatry
has long been primarily defined by its close interconnection with
psychopharmacology and has been perceived this way by practicing physicians. In
recent years, however, the concept of what is "biological" has markedly expanded
and so has the outreach of this approach into the practice of psychiatry. This
article discusses examples showing that biological research methods provide new
impulses for individualized medicine, psychotherapy and understanding
environmental risks and therefore provide the basis for a preemptive and
preventive approach that will be the key to master the challenges posed by the
severe burden of mental illness.
PMID- 26440518
TI - BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAMlow CD11bhigh
Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming.
AB - The transport of antigen from the periphery to the draining lymph node (DLN) is
critical for T-cell priming but remains poorly studied during infection with
Mycobacterium bovis Bacille Calmette-Guerin (BCG). To address this we employed a
mouse model to track the traffic of Dendritic cells (DCs) and mycobacteria from
the BCG inoculation site in the skin to the DLN. Detection of BCG in the DLN was
concomitant with the priming of antigen-specific CD4+ T cells at that site. We
found EpCAMlow CD11bhigh migratory skin DCs to be mobilized during the transport
of BCG to the DLN. Migratory skin DCs distributed to the T-cell area of the LN,
co-localized with BCG and were found in close apposition to antigen-specific CD4+
T cells. Consequently, blockade of skin DC traffic into DLN dramatically reduced
mycobacterial entry into DLN and muted T-cell priming. Interestingly, DC and
mycobacterial entry into the DLN was dependent on IL-1R-I, MyD88, TNFR-I and IL
12p40. In addition, we found using DC adoptive transfers that the requirement for
MyD88 in BCG-triggered migration was not restricted to the migrating DC itself
and that hematopoietic expression of MyD88 was needed in part for full-fledged
migration. Our observations thus identify a population of DCs that contribute
towards the priming of CD4+ T cells to BCG infection by transporting bacilli into
the DLN in an IL-1R-MyD88-dependent manner and reveal both DC-intrinsic and
extrinsic requirements for MyD88 in DC migration.
PMID- 26440521
TI - [Transcranial alternating current stimulation. Entrainment and function control
of neuronal networks].
AB - Transcranial alternating current stimulation (tACS) is a new technique for the
modulation of oscillatory brain activity as measured in the electroencephalogram
(EEG). In contrast to well-established stimulation techniques, such as
transcranial direct current stimulation and transcranial magnetic stimulation,
tACS applies a sinusoidal alternating current at a specific frequency. This
enables the modulation of the amplitude and frequency of endogenous brain
oscillations as well as related cognitive processes. Therefore, the use of tACS
has the possibility to evaluate well-known correlations between brain
oscillations and cognitive processes in terms of causality. Such causal
relationships have been documented in numerous neurocognitive studies on sensory,
motor and perceptual processes; however, the clinical application of tACS is
still in its infancy. In principle, any pathology that can reliably be connected
with brain oscillations of a defined frequency is treatable. A current main focus
of clinical research is on symptoms of Parkinson's disease and to a lesser
degree, tinnitus. For an effective application of tACS it is important to choose
the electrode positions as well as the frequency, intensity and duration of the
stimulation in a theory-based and symptom-related manner. A successful
therapeutic intervention requires the persistence of the tACS effect after
stimulation has ceased. A mechanism that offers not only an explanation to the
origin of persistent tACS effects but is also of high therapeutic benefit is
neural plasticity. Therefore, one current focus of research aims at a better
understanding of tACS after effects.
PMID- 26440520
TI - [Innovative patient-centered care systems: International perspectives].
AB - BACKGROUND: The "Psychiatrie-Enquete" (German Report on the State of Psychiatry)
is 40 years old this year. It has always been inspirational; also
internationally. OBJECTIVE: Which innovative elements of community mental health
services can be found in an international perspective? MATERIALS AND METHODS:
Narrative review. RESULTS: Community mental health care is a lively field with
much research and innovative practice. With assertive community treatment (ACT)
and home treatment (HT), internationally well-evaluated forms of community mental
health care are available. CONCLUSION: Recovery-based and peer-to-peer approaches
hold promise for the future. In terms of mid- and long-term perspectives, an
increase in patient-centering via individualization of mental health care and a
better implementation of community mental health interventions would be desirable
in Germany.
PMID- 26440522
TI - High-Throughput Development of SSR Markers from Pea (Pisum sativum L.) Based on
Next Generation Sequencing of a Purified Chinese Commercial Variety.
AB - Pea (Pisum sativum L.) is an important food legume globally, and is the plant
species that J.G. Mendel used to lay the foundation of modern genetics. However,
genomics resources of pea are limited comparing to other crop species.
Application of marker assisted selection (MAS) in pea breeding has lagged behind
many other crops. Development of a large number of novel and reliable SSR (simple
sequence repeat) or microsatellite markers will help both basic and applied
genomics research of this crop. The Illumina HiSeq 2500 System was used to
uncover 8,899 putative SSR containing sequences, and 3,275 non-redundant primers
were designed to amplify these SSRs. Among the 1,644 SSRs that were randomly
selected for primer validation, 841 yielded reliable amplifications of detectable
polymorphisms among 24 genotypes of cultivated pea (Pisum sativum L.) and wild
relatives (P. fulvum Sm.) originated from diverse geographical locations. The
dataset indicated that the allele number per locus ranged from 2 to 10, and that
the polymorphism information content (PIC) ranged from 0.08 to 0.82 with an
average of 0.38. These 1,644 novel SSR markers were also tested for polymorphism
between genotypes G0003973 and G0005527. Finally, 33 polymorphic SSR markers were
anchored on the genetic linkage map of G0003973 * G0005527 F2 population.
PMID- 26440523
TI - Cholesterol granuloma: a case series & review of literature.
AB - BACKGROUND: Cholesterol granuloma (CG) is a foreign body reaction to crystallized
cholesterol. Orbitofrontal CG is a rare entity with few cases reported in
literature. It is usually seen in young to middle-aged males with a history of
trauma. Computed tomography features include hypodense lesion-causing bone
erosion. CG has typical histopathological features with cholesterol clefts,
multinucleated giant cells, histiocytes, foamy macrophages, and altered blood
pigments. Management is by total excision of the lesion with curettage of the
underlying bone to prevent recurrence. MATERIAL & METHOD: We present an
interventional case series of five patients of orbitofrontal CG, two of them
females. RESULT: None of the patients gave a history of trauma. Management was by
excision of the lesion and curettage confirmed with a 30 degrees rigid
endoscope. CONCLUSION: Cholesterol granulomas can present as superior orbital
mass lesions in the absence of trauma.
PMID- 26440525
TI - Gonadotropin-releasing hormone is prerequisite for the constitutive expression of
pituitary annexin A5.
AB - Annexin A5 (ANXA5), a member of the structurally related family of annexin
proteins, is expressed in pituitary gonadotropes. We previously reported that
ANXA5 expression is stimulated by gonadotropin-releasing hormone (GnRH). In the
present study, we investigated ANXA5 expression in the anterior pituitary gland
of GnRH-deficient mutant hypogonadal (hpg) mice. RT-PCR demonstrated that
luteinizing hormone beta subunit (LHbeta) and ANXA5 mRNA levels were both lower
in the pituitary gland of hpg mice than in wild-type mice. Immunohistochemistry
showed that ANXA5 expression throughout the pituitary gland was very low in hpg
mice, suggesting that ANXA5 is diminished in gonadotropes and also in other cell
types. Subcutaneous administration of a GnRH analogue, des-gly10 (Pro9)-GnRH
ethylamide (1 MUg/day for 7 days), augmented the expression of LHbeta and ANXA5
in the pituitary gland in hpg mice. However, LHbeta- and ANXA5-positive cells did
not show exactly matched spatial distributions. These findings suggest that GnRH
is necessary for constitutive ANXA5 expression in the pituitary gland, not only
in gonadotropes but also in other pituitary gland cell types. A close
relationship between ANXA5 and LHbeta expression was confirmed. It is suggested
that a significant role of ANXA5 in the physiologic secretion of LH.
PMID- 26440524
TI - Scutellarin's Cardiovascular Endothelium Protective Mechanism: Important Role of
PKG-Ialpha.
AB - Scutellarin (SCU), a flavonoid glycoside compound, has been successfully used in
clinic for treatment of ischemic diseases in China. In this report, we checked
the effects of SCU on endothelium dysfunction (ED) of coronary artery (CA)
against myocardial ischemia reperfusion (MIR) injury in vivo. The involvement of
PKG-Ialpha was further studied using cultured endothelial cells subjected to
hypoxia reoxygenation (HR) injury in vitro. In rat MIR model, SCU (45 and 90
mg/kg, iv) significantly reduced ischemic size and restored the endothelium
dependent vasodilation of isolated CA rings. PKG inhibitor Rp-8-Br-cGMP (50
MUg/kg, iv) could ameliorate the protective effects of SCU. Increase in
phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a main substrate
of PKG, at Ser 239 was observed in both heart tissue and serum of SCU-treated
animals. In cultured human cardiac microvascular endothelial cells (HCMECs), SCU
(1 and 10 MUM) dose-dependently protected cell viability and increased the mRNA
and protein level of PKG-Ialpha against HR injury. The activity of PKG was also
increased by SCU treatment. The activation of PKG-1alpha was then studied using
targeted proteomic analysis (MRM-MS) checking the phosphorylation state of the
autophosphorylation domain (aa42-94). Significant decrease in phosphorylation of
PKG-Ialpha at Ser50, Ser72, Ser89 was induced by HR injury while SCU treatment
significantly increased the phosphorylation of PKG-Ialpha, not only at Ser50,
Ser72 and Ser89, but also at Ser44 and Thr58 (two novel phosphorylation domains).
Our results demonstrate PKG-Ialpha might play an important role in the protective
effects of SCU on ED against MIR injury.
PMID- 26440526
TI - Exponential increase of glutamic acid decarboxylase (GAD) antibody titer after
initiating and stopping insulin in a patient with slowly progressive type 1
diabetes.
AB - Few articles have described fluctuations in glutamic acid decarboxylase antibody
(GADAb) levels after a diagnosis of slowly progressive type 1 diabetes (SPIDDM).
Here, we present a case in which GADAb levels exponentially increased after
initiating and stopping insulin. A 64-year-old female patient newly diagnosed
with SPIDDM was admitted and started multiple daily insulin injections. The
patient's GADAb titer was 6.9 U/mL (normal: <1.4 U/mL) and the patient had a type
1 diabetes susceptible HLA class II haplotype known in the Japanese population
as: DRB1*04:05-DQB1*04:01. When the patient's "honeymoon period" set in,
hypoglycemia was observed and the dose of insulin was reduced. Two months after
the diagnosis, 1 unit of insulin glargine/day was being injected and the patient
demonstrated good glycemic control. Subsequently, the patient's home doctor
recommended that insulin injections be stopped. Three months after the diagnosis,
the patient's GADAb titer suddenly increased to 1600 U/mL. The patient's GADAb
titer decreased but was still positive (40 U/mL) 36 months after diagnosis. HbA1c
levels were maintained below 7%, and oral glucose tolerance tests at 10, 26, and
36 months after diagnosis suggested that the patient had preserved insulin
secretion. To the best of our knowledge, this is the first report that describes
exponential increases in GADAb after initiating and stopping insulin in a patient
with SPIDDM.
PMID- 26440527
TI - Endothelin ETA receptor antagonist reverses naloxone-precipitated opioid
withdrawal in mice.
AB - Long-term use of opioids for pain management results in rapid development of
tolerance and dependence leading to severe withdrawal symptoms. We have
previously demonstrated that endothelin-A (ETA) receptor antagonists potentiate
opioid analgesia and eliminate analgesic tolerance. This study was designed to
investigate the involvement of central ET mechanisms in opioid withdrawal. The
effect of intracerebroventricular administration of ETA receptor antagonist BQ123
on morphine and oxycodone withdrawal was determined in male Swiss Webster mice.
Opioid tolerance was induced and withdrawal was precipitated by the opioid
antagonist naloxone. Expression of ETA and ETB receptors, nerve growth factor
(NGF), and vascular endothelial growth factor was determined in the brain using
Western blotting. BQ123 pretreatment reversed hypothermia and weight loss during
withdrawal. BQ123 also reduced wet shakes, rearing behavior, and jumping
behavior. No changes in expression of vascular endothelial growth factor, ETA
receptors, and ETB receptors were observed during withdrawal. NGF expression was
unaffected in morphine withdrawal but significantly decreased during oxycodone
withdrawal. A decrease in NGF expression in oxycodone- but not in morphine
treated mice could be due to mechanistic differences in oxycodone and morphine.
It is concluded that ETA receptor antagonists attenuate opioid-induced withdrawal
symptoms.
PMID- 26440528
TI - Giant Dielectric Permittivity in Ferroelectric Thin Films: Domain Wall Ping Pong.
AB - The dielectric permittivity in ferroelectric thin films is generally orders of
magnitude smaller than in their bulk. Here, we discover a way of increasing
dielectric constants in ferroelectric thin films by ca. 500% by synchronizing the
pulsed switching fields with the intrinsic switching time (nucleation of domain
plus forward growth from cathode to anode). In a 170-nm lead zirconate titanate
thin film with an average grain size of 850 nm this produces a dielectric
constant of 8200 with the maximum nucleus density of 3.8 MUm(-2), which is one to
three orders of magnitude higher than in other dielectric thin films. This
permits smaller capacitors in memory devices and is a step forward in making
ferroelectric domain-engineered nano-electronics.
PMID- 26440529
TI - Quantifying Semantic Linguistic Maturity in Children.
AB - We propose a method to quantify semantic linguistic maturity (SELMA) based on a
high dimensional semantic representation of words created from the co-occurrence
of words in a large text corpus. The method was applied to oral narratives from
108 children aged 4;0-12;10. By comparing the SELMA measure with maturity ratings
made by human raters we found that SELMA predicted the rating of semantic
maturity made by human raters over and above the prediction made using a child's
age and number of words produced. We conclude that the semantic content of
narratives changes in a predictable pattern with children's age and argue that
SELMA is a measure quantifying semantic linguistic maturity. The study opens up
the possibility of using quantitative measures for studying the development of
semantic representation in children's narratives, and emphasizes the importance
of word co-occurrences for understanding the development of meaning.
PMID- 26440531
TI - Aryl Hydrocarbon Receptor Activation in Acne Vulgaris Skin: A Case Series from
the Region of Naples, Italy.
AB - BACKGROUND: Dioxins are persistent organic pollutants present in the environment.
They exert their biological effects by binding to an intracellular receptor, the
aryl hydrocarbon receptor (AhR). Activation of AhR leads to the induction of
cytochrome p450 1A1 (CYP1A1). Expression of CYP1A1 in human skin is a key marker
for AhR activation, and it may induce comedogenesis resulting in acne-like
lesions known as chloracne/metabolising acquired dioxin-induced skin hamartomas
(MADISH). The contribution of this pathway in patients seen in a busy acne clinic
is unknown. MATERIALS AND METHODS: We explored the expression of CYP1A1 by
immunohistochemistry in the acne lesions of 16 patients living in the region of
Naples, Italy, where epidemiological studies have suggested a possibly increased
exposure to environmental dioxins. A composite score to outline potential
components of the chloracne/MADISH histological pattern was used. RESULTS: CYP1A1
expression was observed in 11 lesions (69%) and was distributed in sebaceous
glands, follicular epithelium, cystic wall and endothelial cells. The
histological score for chloracne/MADISH was 'likely' in 3 cases and 'possible' in
11 cases. Compared to current data on CYP1A1 expression in the skin of 67
patients with proven exposure to AhR agonists, these data indicate a high
incidence of AhR activation in this series. CONCLUSION: This is the first study
analysing AhR activation in skin in a series of patients from a hospital-based
acne clinic. It provides information for future controlled prospective studies.
The significance of CYP1A1 expression in terms of AhR ligand exposure is
discussed.
PMID- 26440530
TI - A comparison of anti-HER2 IgA and IgG1 in vivo efficacy is facilitated by high N
glycan sialylation of the IgA.
AB - Monomeric IgA has been proposed as an alternative antibody format for cancer
therapy. Here, we present our studies on the production, purification and
functional evaluation of anti-HER2 IgA antibodies as anti-cancer agents in
comparison to the anti-HER2 IgG1 trastuzumab. MALDI-TOF MS analysis showed
profound differences in glycosylation traits across the IgA isotypes and cell
lines used for production, including sialylation and linkage thereof,
fucosylation (both core and antennary) and the abundance of high-mannose type
species. Increases in sialylation proved to positively correlate with in vivo
plasma half-lives. The polymerization propensity of anti-HER2 IgA2m2 could be
suppressed by an 18-aa deletion of the heavy chain tailpiece - coinciding with
the loss of high-mannose type N-glycan species - as well as by 2 cysteine to
serine mutations at positions 320 and 480. The HER2 F(ab')2-mediated anti
proliferative effect of the IgA2m1 and IgA2m2 subtypes was similar to IgG1,
whereas the IgA1 isotype displayed considerably lower potency and efficacy. The
Fc-mediated induction of antibody-dependent cell-mediated cytotoxicity (ADCC)
using human whole blood ADCC assays did not demonstrate such clear differences
between the IgA isotypes. However, the potency of the anti-HER2 IgA antibodies in
these ADCC assays was found to be significantly lower than that of trastuzumab.
In vivo anti-tumor activity of the anti-HER2 IgA antibodies was compared to that
of trastuzumab in a BT-474 breast cancer xenograft model. Multiple dosing and
sialylation of the IgA antibodies compensated for the short in vivo half-life of
native IgA antibodies in mice compared to a single dose of IgG1. In the case of
the IgA2m2 antibody, the resulting high plasma exposure levels were sufficient to
cause clear tumor stasis comparable to that observed for trastuzumab at much
lower plasma exposure levels.
PMID- 26440532
TI - Cardioprotection mechanism of mangiferin on doxorubicin-induced rats: Focus on
intracellular calcium regulation.
AB - CONTEXT: The molecular mechanism of doxorubicin (DOX) cardiotoxicity involves
overproduction of free radicals that leads to intracellular calcium dysregulation
and apoptosis. Mangiferin (MGR), a naturally occurring glucosylxanthone, has
antioxidant and cardioprotective properties. However, its cardioprotection
mechanism has yet to be revealed. OBJECTIVE: This study determines whether the
cardioprotective effect of MGR is caused by its effect on intracellular calcium
regulation. MATERIALS AND METHODS: Male Sprague-Dawley rats were induced by DOX
intraperitoneally with a total dose of 15 mg/kg bw. MGR was given orally at the
doses of 30 and 60 mg/kg bw/d for seven consecutive weeks. The parameters
examined were mRNA expression levels of proinflammatory cytokine gene (TNF
alpha), calcium regulatory gene (SERCA2a) and proapoptotic genes (caspase-9 and
caspase-12), as well as cytosolic and mitochondrial calcium levels. RESULTS:
Treatment with MGR at 60 mg/kg bw/d significantly decreased the mRNA expression
levels of TNF-alpha by 44.55% and caspase-9 by 52.79%, as well as the cytosolic
calcium level by 24.15% (p < 0.05). SERCA2a and caspase-12 expressions were only
slightly affected (27.27% increase and 24.85% decrease for SERCA2a and caspase
12, respectively, p > 0.05). Meanwhile, MGR 30 mg/kg bw/d gave insignificant
results in all parameters. DISCUSSION AND CONCLUSION: MGR protected against DOX
induced cardiac inflammation and apoptosis via down-regulation of proapoptotic
and proinflammatory gene expressions, upregulation of SERCA2a gene expression,
and normalization of cytosolic calcium level. Thus, the cardioprotective effect
of MGR is at least in part due to the regulation of intracellular calcium
homeostasis.
PMID- 26440533
TI - Feasibility and significance of preclinical diagnosis in hypertrophic
cardiomyopathy.
AB - Preclinical diagnosis in hypertrophic cardiomyopathy (HCM) refers to the
detection of functional or histopathological abnormalities in subjects who carry
any HCM-causing gene mutation, before or even without the development of left
ventricular hypertrophy [genotype(+)/phenotype(-)subjects]. The concept that HCM
pathology may exist in the absence of left ventricular hypertrophy is quite old
but the ability to recognize the presence of early myocardial changes is quite
new. Lessons from animal models have shown that in experimental human HCM,
myocardial cell mechanical dysfunction precedes histopathological changes, such
as myocyte disarray, fibrosis, and hypertrophy. Several clinical reports have
demonstrated that the majority of HCM genotype(+)/phenotype(-) subjects display
myocardial functional or histopathological changes, such as reduced tissue
Doppler imaging-derived systolic and diastolic velocities, abnormal
electrocardiogram, cardiac magnetic resonance-visualized myocardial crypts,
mitral leaflet elongation, and evidence of a fibrotic state, such as increased
type I procollagen synthesis, cardiac magnetic resonance-increased myocardial
extracellular volume, and late gadolinium myocardial enhancement. All these signs
have been proposed as preclinical markers of HCM. At present the separation of
such a group of subjects in the early phase of their disease provides the
opportunity to test new therapies to prevent the development of fibrosis,
hypertrophy, and dysfunction.
PMID- 26440534
TI - The heartbreak of psoriasis: a review of cardiovascular risk in patients with
psoriasis.
AB - Psoriasis is a common, chronic, autoimmune condition characterized by excessive
growth and differentiation of keratinocytes that affects approximately 1% to 3%
of the general population in the United States. Mounting evidence has led to an
increasing awareness that psoriasis as a disease is more than "skin deep" and
that it shares systemic manifestations with other chronic inflammatory diseases
such as Crohn's and diabetes mellitus. Recent studies have not only shown an
increased prevalence of cardiovascular risk factors in psoriasis but have also
identified psoriasis as an independent risk factor for developing cardiovascular
disease. This calls for an approach beyond managing traditional risk factors,
which remain the standard guidelines at present.
PMID- 26440535
TI - Microscopic identification of novel cell types in the integument of larval lake
sturgeon, Acipenser fulvescens.
AB - Osmoregulation, respiration, nutrient/mineral transport, and defense mechanisms
are all evident in the integument of fish. The role of the integument in these
physiological processes is particularly important during early life history in
larval fishes, as functional systems such as the gills and gastrointestinal tract
are not fully developed. Using a variety of microscopy techniques, we describe
the morphology of keratinocytes, mitochondria rich cells, ciliated cells and
mucous cells of the skin, yolk sac, and gills. The cytology we observed was
similar to previous studies describing the integument of larval fish, however, we
have also identified two novel cell types on the integument of larval Lake
Sturgeon, Acipenser fulvescens, between 9 and 34 days post fertilization. Our
detailed analysis included a multifaceted microscopy approach using scanning
electron, transmission electron, and light microscopy to elucidate the histology
of the tissue and cellular morphology in addition to quantification and
distribution of these novel cell types. The first cell type had a characteristic
ampullary shape with a central cavity and a pore opening at the surface. The
second, located on the free surface of the epidermis, had an uneven plasma
membrane surface. Based on the abundance of secretory vesicles, organelles
necessary for protein synthesis, and the lack of neural connection in both cell
types, we propose these cells to be involved in the release of semiochemicals
that may act as a pheromone, alarm substance, or chemical defense mechanism.
PMID- 26440536
TI - 4pi electrocyclisation in domino processes: contemporary trends and synthetic
applications towards natural products.
AB - Recent most instructive and reliable literature reports which deal with domino
processes involving conrotatory 4pi electrocyclic reactions, along with a precise
mechanistic insight and latest synthetic applications towards biologically active
natural products are concisely reviewed. To inspire further research in this
domain, a real insight into the overarching emerging themes and potential
imminent prospects is also provided.
PMID- 26440537
TI - Advancing the 3Rs in regulatory ecotoxicology: A pragmatic cross-sector approach.
AB - The ecotoxicity testing of chemicals for prospective environmental safety
assessment is an area in which a high number of vertebrates are used across a
variety of industry sectors. Refining, reducing, and replacing the use of animals
such as fish, birds, and amphibians for this purpose addresses the ethical
concerns and the increasing legislative requirements to consider alternative test
methods. Members of the UK-based National Centre for the Replacement, Refinement
and Reduction of Animals in Research (NC3Rs) Ecotoxicology Working Group,
consisting of representatives from academia, government organizations, and
industry, have worked together over the past 6 y to provide evidence bases to
support and advance the application of the 3Rs in regulatory ecotoxicity testing.
The group recently held a workshop to identify the areas of testing, demands, and
drivers that will have an impact on the future of animal use in regulatory
ecotoxicology. As a result of these discussions, we have developed a pragmatic
approach to prioritize and realistically address key opportunity areas, to enable
progress toward the vision of a reduced reliance on the use of animals in this
area of testing. This paper summarizes the findings of this exercise and proposes
a pragmatic strategy toward our key long-term goals-the incorporation of reliable
alternatives to whole-organism testing into regulations and guidance, and a
culture shift toward reduced reliance on vertebrate toxicity testing in routine
environmental safety assessment. Integr Environ Assess Manag 2016;12:417-421. (c)
2015 SETAC.
PMID- 26440538
TI - Differential levels of p75NTR ectodomain in CSF and blood in patients with
Alzheimer's disease: a novel diagnostic marker.
AB - Alzheimer's disease (AD) is the primary cause of dementia in the elderly. The
ectodomain of p75 neurotrophin receptor (p75NTR-ECD) has been suggested to play
important roles in regulating beta-amyloid (Abeta) deposition and in protecting
neurons from the toxicity of soluble Abeta. However, whether and how the serum
and cerebrospinal fluid (CSF) levels of p75NTR-ECD change in patients with AD are
not well documented. In the present study, we determined the concentrations of
serum p75NTR-ECD in an AD group, a Parkinson disease group and a stroke group, as
well as in a group of elderly controls without neurological disorders (EC). We
also determined the levels of CSF p75NTR-ECD in a subset of the AD and EC groups.
Our data showed that a distinct p75NTR-ECD profile characterized by a decreased
CSF level and an increased serum level was present concomitantly with AD patients
but not with other diseases. p75NTR-ECD levels in both the serum and CSF were
strongly correlated with Mini-Mental State Examination (MMSE) scores and showed
sound differential diagnostic value for AD. Moreover, when combining CSF Abeta42,
CSF Abeta42/40, CSF ptau181 or CSF ptau181/Abeta42 with CSF p75NTR-ECD, the area
under the receiver operating characteristic curve (AUC) and diagnostic accuracies
improved. These findings indicate that p75NTR-ECD can serve as a specific
biomarker for AD and the determination of serum and CSF p75NTR-ECD levels is
likely to be helpful in monitoring AD progression.
PMID- 26440540
TI - Use of the second-generation antipsychotic, risperidone, and secondary weight
gain are associated with an altered gut microbiota in children.
AB - The atypical antipsychotic risperidone (RSP) is often associated with weight gain
and cardiometabolic side effects. The mechanisms for these adverse events are
poorly understood and, undoubtedly, multifactorial in etiology. In light of
growing evidence implicating the gut microbiome in the host's energy regulation
and in xenobiotic metabolism, we hypothesized that RSP treatment would be
associated with changes in the gut microbiome in children and adolescents. Thus,
the impact of chronic (>12 months) and short-term use of RSP on the gut
microbiome of pediatric psychiatrically ill male participants was examined in a
cross-sectional and prospective (up to 10 months) design, respectively. Chronic
treatment with RSP was associated with an increase in body mass index (BMI) and a
significantly lower ratio of Bacteroidetes:Firmicutes as compared with
antipsychotic-naive psychiatric controls (ratio=0.15 vs 1.24, respectively;
P<0.05). Furthermore, a longitudinal observation, beginning shortly after onset
of RSP treatment, revealed a gradual decrease in the Bacteroidetes:Firmicutes
ratio over the ensuing months of treatment, in association with BMI gain. Lastly,
metagenomic analyses were performed based on extrapolation from 16S ribosomal RNA
data using the software package, Phylogenetic Investigation of Communities by
Reconstruction of Unobserved States (PICRUSt). Those data indicate that gut
microbiota dominating the RSP-treated participants are enriched for pathways that
have been implicated in weight gain, such as short-chain fatty acid production.
PMID- 26440539
TI - Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4
associated with nicotine dependence.
AB - We conducted a 1000 Genomes-imputed genome-wide association study (GWAS) meta
analysis for nicotine dependence, defined by the Fagerstrom Test for Nicotine
Dependence in 17 074 ever smokers from five European-ancestry samples. We
followed up novel variants in 7469 ever smokers from five independent European
ancestry samples. We identified genome-wide significant association in the alpha
4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P=8.0 *
10(-9) across all the samples for rs2273500-C (frequency=0.15; odds ratio=1.12
and 95% confidence interval=1.08-1.17 for severe vs mild dependence). rs2273500
C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript
predicted to be targeted for nonsense-mediated decay, was associated with
decreased CHRNA4 expression in physiologically normal human brains (lowest P=7.3
* 10(-4)). Importantly, rs2273500-C was associated with increased lung cancer
risk (N=28 998, odds ratio=1.06 and 95% confidence interval=1.00-1.12), likely
through its effect on smoking, as rs2273500-C was no longer associated with lung
cancer after adjustment for smoking. Using criteria for smoking behavior that
encompass more than the single 'cigarettes per day' item, we identified a common
CHRNA4 variant with important regulatory properties that contributes to nicotine
dependence and smoking-related consequences.
PMID- 26440542
TI - Reduced cortical expression of a newly identified splicing variant of the DLG1
gene in patients with early-onset schizophrenia.
AB - The human discs, large homolog 1 gene (DLG1) is mapped to the schizophrenia
susceptibility locus 3q29, and it encodes a scaffold protein that interacts with
the N-methyl-D-aspartate receptor presumably dysregulated in schizophrenia. In
the current study, we have newly identified a splicing variant of DLG1, which is
transcribed from an unreported 95-base-pair exon (exon 3b) and is labeled 3b(+).
We investigated the mRNA expression of 3b(+) in the post-mortem dorsolateral
prefrontal cortices of patients with psychiatric disorders, obtained from The
Stanley Medical Research Institute, and examined the potential association of the
expression with the genotype of the single-nucleotide polymorphism (SNP)
rs3915512 located within exon 3b. A real-time quantitative reverse transcriptase
polymerase chain reaction revealed that the mRNA levels of 3b(+) were
significantly reduced in patients with early-onset schizophrenia (onset at <18
years old, P=0.0003) but not in those with non-early-onset schizophrenia, early
onset or non-early-onset bipolar disorder or in the controls. Furthermore, the
genotype at the rs3915512 SNP was closely associated with the levels of 3b(+)
mRNA expression. It is inferred that the T allele fails to meet the exonic
splicing enhancer consensus, thus resulting in skipping of exon 3b, leading to
the expression of 3b(-) (the previously known DLG1 variant) but not 3b(+).
Because all the subjects with early-onset schizophrenia in the current study
possess the T/T genotype, the reduced level of the DLG1 3b(+) transcript may be
involved in the susceptibility and/or pathophysiology of early-onset
schizophrenia.
PMID- 26440541
TI - Right external globus pallidus changes are associated with altered causal
awareness in youth with depression.
AB - Cognitive impairment is a functionally disabling feature of depression
contributing to maladaptive decision-making, a loss of behavioral control and an
increased disease burden. The ability to calculate the causal efficacy of ones
actions in achieving specific goals is critical to normal decision-making and, in
this study, we combined voxel-based morphometry (VBM), shape analysis and
diffusion tensor tractography to investigate the relationship between cortical
basal ganglia structural integrity and such causal awareness in 43 young subjects
with depression and 21 demographically similar healthy controls. Volumetric
analysis determined a relationship between right pallidal size and sensitivity to
the causal status of specific actions. More specifically, shape analysis
identified dorsolateral surface vertices where an inward location was correlated
with reduced levels of causal awareness. Probabilistic tractography revealed that
affected parts of the pallidum were primarily connected with the striatum, dorsal
thalamus and hippocampus. VBM did not reveal any whole-brain gray matter regions
that correlated with causal awareness. We conclude that volumetric reduction
within the indirect pathway involving the right dorsolateral pallidum is
associated with reduced awareness of the causal efficacy of goal-directed actions
in young depressed individuals. This causal awareness task allows for the
identification of a functionally and biologically relevant subgroup to which more
targeted cognitive interventions could be applied, potentially enhancing the long
term outcomes for these individuals.
PMID- 26440543
TI - Histamine H4 receptor knockout mice display reduced inflammation in a chronic
model of atopic dermatitis.
AB - BACKGROUND: The histamine H4 receptor (H4R) was brought into focus as a new
therapeutic target for the treatment of allergic disorders such as atopic
dermatitis (AD). H4R antagonists have already been tested in several animal
models of AD, but these studies have yielded conflicting results. MATERIAL AND
METHODS: The development of ovalbumin-induced AD-like skin lesions was analysed
in H4R(-/-) mice and in H4R antagonist (JNJ28307474)-treated mice. RESULTS: H4R(
/-) mice showed a clear amelioration of the skin lesions, with a diminished
influx of inflammatory cells and a reduced epidermal hyperproliferation at
lesional skin sites. H4R(-/-) mice had a reduced amount of ovalbumin-specific
IgE, a reduced number of splenocytes and lymph node cells with a decreased number
of CD4+ T cells. The H4R modulated the cytokine secretion of CD4+ T cells and
splenocytes and altered the cellular profile in the lymph nodes. The anti
inflammatory effect could only partially be mimicked by JNJ28307474 and only when
the H4R antagonist was given during sensitization and challenge and not when
JNJ28307474 was only given during the provocation phase of the allergic reaction.
CONCLUSION: The H4R modulates inflammation in a chronic allergic dermatitis
setting. However, results of this study indicate that it is necessary to block
the H4R during ontogeny and development of the allergic inflammation.
PMID- 26440544
TI - What is the mechanism effect that links social support to coping and
psychological outcome within individuals affected by prostate cancer? Real time
data collection using mobile technology.
AB - PURPOSE: Unmet support needs are prevalent in men affected by prostate cancer.
Moreover, little is known about the optimal type of social support, or its
mechanism effect between coping and emotional outcome in men affected by this
disease to identify areas for clinical intervention. This study aimed to
empirically test the propositions of social support theory in "real time" within
individual men living with and beyond prostate cancer. METHODS: Purposeful sub
sample from a larger prospective longitudinal study of prostate cancer survivors,
took part in real time data collection using mobile technology. Self-reports were
collected for 31 days prompted by an audio alarm 3 times per day (a total of 93
data entries) for each of the 12 case studies. Electronic data were analysed
using time series analysis. RESULTS: Majority of response rates were >90%. Men
reported a lack of satisfaction with their support over time. Testing the
propositions of social support theory "within individuals" over time demonstrated
different results for main effect, moderation and mediation pathways that linked
coping and social support to emotional outcome. For two men, negative effects of
social support were identified. For six men the propositions of social support
theory did not hold considering their within-person data. CONCLUSION: This
innovative study is one of the first, to demonstrate the acceptability of e
health technology in an ageing population of men affected by prostate cancer.
Collectively, the case series provided mixed support for the propositions of
social support theory, and demonstrates that "one size does not fit all".
PMID- 26440545
TI - Variation in bioaccumulation of persistent organic pollutants based on octanol
air partitioning: Influence of respiratory elimination in marine species.
AB - Risk assessments of persistent organic pollutants (POPs) are often based on
octanol-water (KOW) partitioning dynamics and may not adequately reflect
bioaccumulation in air-breathing organisms. It has been suggested that compounds
with low KOW and high octanol-air partitioning (KOA) coefficients have the
potential to bioaccumulate in air-breathing organisms, including marine mammals.
Here we evaluate differences in concentrations of POPs for two trophically
matched Arctic species, spotted seal (Phoca largha) and sheefish (Stenodus
leucichthys). We compared concentrations of 108 POPs in matched tissues (liver
and muscle) across three ranges of KOW. We found a significant positive
correlation between POP concentration and log KOA in spotted seal tissues for low
log KOW compounds (log KOW <5.5, p<0.05). This provides further evidence for
empirical models and observed bioaccumulation patterns in air-breathing
organisms, and highlights the potential for bioaccumulation of these compounds in
Arctic marine mammals.
PMID- 26440546
TI - The combined transverse upper gracilis and profunda artery perforator (TUGPAP)
flap for breast reconstruction.
AB - BACKGROUND: Surgical options for breast reconstruction include alloplastic and
autogenous reconstructions. In autologous cases where the abdomen is not a
suitable primary donor site, secondary donor sites such as the thigh or buttock
are considered. The aim of this report is to describe a novel approach, the
combined transverse upper gracilis and profunda artery perforator (TUGPAP) flap,
aimed at medium to large volume breast reconstruction, with a single donor site
used per breast. METHODS: Between January 2011 and June 2013, 32 consecutive
unilateral immediate breast reconstruction cases were performed using free flaps.
In nine cases, patients had previously undergone abdominal surgery, therefore
abdominal flaps were excluded and TUGPAP flaps were performed. The TUGPAP flap
consisted of the combination of two well-described flaps: the transverse upper
gracilis (TUG) and the profunda artery perforator (PAP) flap. All TUGPAP flaps
were based on two pedicles: the ascending branch of the medial circumflex femoral
artery (MCFA) for the TUG component, and the profunda artery perforator itself
for the PAP component. RESULTS: The mean size of the harvested skin paddle was
28.6 * 8 cm2 (range, 27 * 7 cm2 to 30 * 9 cm2). The average length of the TUG
flap pedicle was 7 cm (range, 6-8 cm) and the PAP flap pedicle was 9 cm (range,
8.5-10 cm). The flap survival rate was 100% with no re-exploration, and no
partial flap loss. Post-operatively there was one case of persistent donor site
seroma, which was managed conservatively. CONCLUSION: With appropriate patient
selection and surgical technique the TUGPAP flap could be a valuable option as an
alternative method for autologous breast reconstruction. (c) 2015 Wiley
Periodicals, Inc. Microsurgery, 2015.
PMID- 26440547
TI - A unique alpha dosimetry technique using Gafchromic EBT3((r)) film and
feasibility study for an activity calibrator for alpha-emitting
radiopharmaceuticals.
AB - OBJECTIVE: To develop an alpha dosimetry technique for activity calibration of
alpha-emitting radiopharmaceuticals using the Gafchromic((r)) EBT3 (Gaf-EBT3)
radiochromic film (International Speciality product, Wayne, NJ). METHODS: The Gaf
EBT3 has a tissue equivalent radiosensitive layer (approximately 28 MUm)
sandwiched between two 100-MUm thick polyester sheaths, thereby making it
insensitive to alpha particles. We have split a Gaf-EBT3 sheet using a surgical
scalpel to remove one of the polyester protective layers and covered the
radiosensitive layer with thin Mylar((r)) foil (Goodfellow Cambridge Limited,
Huntingdon, UK) (2.5 MUm). Small pieces of modified film were exposed at contact
with a 560-Bq thin (241)Am source for 5, 10, 24 and 94 h. The optical density of
the films was evaluated using an optical densitometer. The alpha energy spectra
of the (241)Am source were recorded using a Si(Li) surface barrier detector.
RESULTS: Time-integrated specific alpha surface activity (kBq cm(-2) h) was
represented as a function of optical density. CONCLUSION: By removing one of the
100 MUm thick polyester protective layers, the authors have modified the Gaf-EBT3
film to a sensitive alpha dosemeter. The calibration function relevant to a
(241)Am reference source was evaluated from the optical densities of the
dosemeter foils. Furthermore, calibration functions for important alpha emitters
such as (223)Ra, (225)Ac or (210)Bi were parameterized from the (241)Am reference
data. ADVANCES IN KNOWLEDGE: The authors have developed and tested the principle
of a clinical alpha dosemeter using Gaf-EBT3 radiochromic films originally
developed for photon dosimetry. This novel, user-friendly technique could be
implemented in quality assurance and calibration procedures of important alpha
emitting radiopharmaceuticals prior to their clinical applications.
PMID- 26440548
TI - MRI and thallium features of pigmented villonodular synovitis and giant cell
tumours of tendon sheaths: a retrospective single centre study of imaging and
literature review.
AB - OBJECTIVE: The purpose of this study was to characterize the MRI and thallium-201
((201)TI) scintigraphy attributes of pigmented villonodular synovitis (PVNS) and
giant cell tumours of tendon sheaths (GCTTS). The epidemiology of these uncommon
lesions was also assessed and less commonly encountered pathology reported on
including multifocality, necrosis and concurrent malignancy. METHODS: A
retrospective single centre review of MRI and (201)TI scintigraphy findings for
83 surgically proven or biopsy-proven consecutive cases of PVNS was undertaken.
Radiological findings including lesion size, (201)TI uptake (as a marker of
metabolic activity), location, extent and patient demographics were correlated
with biopsy and surgical specimen histology. Typical appearances are described,
as well as less common imaging manifestations. The study period encompassed all
patients presenting or referred to a tertiary bone and soft-tissue tumour
referral centre with PVNS or GCTTS between 1 January 2007 and the 1 December
2013. RESULTS: Lesions occur most commonly around the knee joint in the fourth
decade of life, with younger patients showing a tendency to occur in the hip.
Features of PVNS and GTTS include bone erosion, ligamentous and cartilage
replacement, muscle infiltration and multifocality. MR signal characteristics
were variable but post-contrast enhancement was near-universal. 14 of 83 cases
showed no uptake of (201)TI and revealed a statistically significant smaller
average axial dimension of 19.8 mm than lesions displaying active (201)TI uptake
of 36.4 mm, p = 0.016. Four lesions demonstrated central necrosis on gross
histology, two of each from both the (201)TI-avid and (201)TI-non-avid groups.
CONCLUSION: MR is the imaging modality of choice when considering the diagnosis
of these uncommon tumours. (201)TI scintigraphy as a marker of metabolic activity
further adds minimal value although small lesions can appear to lack (201)TI
avidity. ADVANCES IN KNOWLEDGE: This article depicts typical imaging findings of
PVNS/GCTTS and also a subset of lesions that demonstrate no uptake on metabolic
functional imaging, namely smaller sized lesions irrespective of anatomical
location. This represents an important departure from previously documented
imaging manifestations, whereby an absence of isotope accumulation suggested
exclusion of these lesions from the differential diagnosis. These findings have
important implications when considering the diagnosis of these uncommon lesions
and may be important when interpreting post-treatment response. We suggest that
further investigation, for example, with MRI is valuable in order to clarify
potential post-treatment response, as well as the use of alternate functional
imaging modalities such as positron emission tomography (PET), to further
corroborate these findings.
PMID- 26440549
TI - Can PEP-3 Provide a Cognitive Profile in Children with ASD? A Comparison Between
the Developmental Ages of PEP-3 and IQ of Leiter-R.
AB - BACKGROUND: The assessment of the intelligence quotient (IQ) in children with
autism spectrum disorder (ASD) is important to plan a detailed therapeutic
educative programme. The aim of the study was to evaluate the usefulness of the
Psychoeducational Profile-third edition (PEP-3) to estimate the general cognitive
development of children with ASD. METHOD: We recruited 30 children with ASD
assessed with the Leiter International Performance Scale-Revised (Leiter-R) and
the PEP-3. We compared the IQ of the Leiter-R with the developmental level (DL)
of PEP-3. RESULTS: The findings showed a significant positive correlation between
IQ with DL of the cognitive verbal/pre-verbal (P = 0.0005), DL of the area of
expressive language (P = 0.0004), DL of the area of receptive language (P =
0.0001), DL of fine motor (P = 0.0066), DL of gross motor (P = 0.0217), DL of
visuo-motor imitation (P = 0.02), DL of communication (P = 0.0001) and DL of
motor (P = 0.0063). CONCLUSIONS: These findings show that the DLs could be
considered as indicators of cognitive functioning in ASD.
PMID- 26440550
TI - Neuromodulation for cardiac arrhythmia.
AB - The autonomic nervous system is known to play a significant role in the genesis
and maintenance of arrhythmias. Neuromodulation, mostly designed to increase the
parasympathetic tone and suppress the sympathetic tone, has become an emerging
therapeutic strategy for the treatment of arrhythmias. Emerging therapeutic
approaches include cervical vagal stimulation, transcutaneous auricular vagal
stimulation, baroreceptor activation therapy spinal cord stimulation,
ganglionated plexi ablation, renal sympathetic denervation, and left cardiac
sympathetic denervation.
PMID- 26440551
TI - Implantable devices in young patients: Hitting the reset button on risk versus
benefit.
PMID- 26440552
TI - Mechanical thrombectomy as an alternative to thrombolysis in embolic stroke.
PMID- 26440553
TI - Detecting association of rare and common variants by adaptive combination of P
values.
AB - Genome-wide association studies (GWAS) can detect common variants associated with
diseases. Next generation sequencing technology has made it possible to detect
rare variants. Most of association tests, including burden tests and nonburden
tests, mainly target rare variants by upweighting rare variant effects and
downweighting common variant effects. But there is increasing evidence that
complex diseases are caused by both common and rare variants. In this paper, we
extend the ADA method (adaptive combination of P-values; Lin et al., 2014) for
rare variants only and propose a RC-ADA method (common and rare variants by
adaptive combination of P-values). Our proposed method combines the per-site P
values with the weights based on minor allele frequencies (MAFs). The RC-ADA is
robust to directions of effects of causal variants and inclusion of a high
proportion of neutral variants. The performance of the RC-ADA method is compared
with several other association methods. Extensive simulation studies show that
the RC-ADA method is more powerful than other association methods over a wide
range of models.
PMID- 26440554
TI - Benzophenone 1 induced photogenotoxicity and apoptosis via release of cytochrome
c and Smac/DIABLO at environmental UV radiation.
AB - Solar UV radiation is main factor of photocarcinogenesis, photoageing, and
phototoxicity; thus, protection from UV radiation is major concern. Sunscreens
containing UV filters are suggested as sun safe practices, but safety of UV
filters remains in controversies. Benzophenone-1 (BP1) is commonly used in
sunscreens as UV blocker. We assessed the photogenotoxicity and apoptotic
parameters in human keratinocytes (HaCaT cells) by western blot,
immunocytochemistry, flowcytometry, comet assay and TEM imaging. Our results
exposed that BP1 photosensitized and generated intracellular ROS (2.02 folds)
under sunlight/UVR. Decrease in cell viability was recorded as 80.06%, 60.98% and
56.24% under sunlight, UVA and UVB, respectively. Genotoxic potential of BP1 was
confirmed through photomicronuclei and CPDs formation. BP1 enhanced lipid
peroxidation and leakage of LDH enzyme (61.7%). Apoptotic cells were detected by
AnnexinV/PI staining and sub G1 population of cell cycle. BP1 induced up
regulation of apoptotic proteins Bax/Bcl2 ratio, Apaf-1, cytochrome c,
Smac/DIABLO and cleaved caspase 3 was noticed. Down regulation of pro caspase 3
was inhibited by Z-VAD-fmk (inhibitor of caspase). Thus, study established the
involvement of BP1 in photogenotoxicity and apoptosis via release of cytochrome c
and Smac/DIABLO. These findings suggest sunscreen user to avoid BP1 in cosmetics
preparation for its topical application.
PMID- 26440555
TI - Transition and duration in disability: New evidence from administrative data.
AB - BACKGROUND: In recent decades demographic changes (low fertility rates, increased
life expectancy...) in most OECD countries, have brought profound changes in the
population pyramid, with several effects in the welfare of society. One of them
is the increase in the number of people with disabilities, since age is a
determining factor in the emergence of this dependency. OBJECTIVE/HYPOTHESIS:
This paper studies the probability to enter and transit in and from a disability
state, as well as its associated mortality, by attending to the distinction
between the initial disability level and the process that leads on from it, and
by addressing whether and how education, age and income affect this transition.
METHODS: Applying a Markov model and a survival analysis to new Spanish
administrative data set (Muestra Continua de Vida Laboral (MCVL)) we estimate the
probability that a person changes the state of disability and the duration of her
progression in each case. RESULTS: We find that people with an initial state of
disability have a higher propensity to change status and take less time to
transit amongst different stages than those who have no disability. Men do so
more frequently than women and income have negative effects on the transition.
CONCLUSIONS: These results may help to incorporate into welfare programs some
protection mechanisms for delaying transitions and target the most fragile
population groups.
PMID- 26440557
TI - Anion-specific aggregation induced phosphorescence emission (AIPE) in an ionic
iridium complex in aqueous media.
AB - Efficient aggregation induced phosphorescence emission (AIPE) of an ionic Ir(iii)
complex occurs when the counterion (PF6(-)) is exchanged specifically by ClO4(-)
in aqueous media. As a result, a rapid, highly selective "turn-on" phosphorescent
response to ClO4(-) is observed in aqueous media. These studies pave the way for
a new efficient phosphorescence-based detection strategy for anions.
PMID- 26440556
TI - Systematic overview of economic evaluations of health-related rehabilitation.
AB - BACKGROUND: Health related rehabilitation is instrumental in improving
functioning and promoting participation by people with disabilities. To make
clinical and policy decisions about health-related rehabilitation, resource
allocation and cost issues need to be considered. OBJECTIVES: To provide an
overview of systematic reviews (SRs) on economic evaluations of health-related
rehabilitation. METHODS: We searched multiple databases to identify relevant SRs
of economic evaluations of health-related rehabilitation. Review quality was
assessed by AMSTAR checklist. RESULTS: We included 64 SRs, most of which included
economic evaluations alongside randomized controlled trials (RCTs). The review
quality was low to moderate (AMSTAR score 5-8) in 35, and high (score 9-11) in 29
of the included SRs. The included SRs addressed various health conditions,
including spinal or other pain conditions (n = 14), age-related problems (11),
stroke (7), musculoskeletal disorders (6), heart diseases (4), pulmonary (3),
mental health problems (3), and injury (3). Physiotherapy was the most commonly
evaluated rehabilitation intervention in the included SRs (n = 24). Other
commonly evaluated interventions included multidisciplinary programmes (14);
behavioral, educational or psychological interventions (11); home-based
interventions (11); complementary therapy (6); self-management (6); and
occupational therapy (4). CONCLUSIONS: Although the available evidence is often
described as limited, inconsistent or inconclusive, some rehabilitation
interventions were cost-effective or showed cost-saving in a variety of
disability conditions. Available evidence comes predominantly from high income
countries, therefore economic evaluations of health-related rehabilitation are
urgently required in less resourced settings.
PMID- 26440558
TI - CARD9 mutation linked to Corynespora cassiicola infection in a Chinese patient.
AB - Corynespora cassiicola is a plant pathogen associated with leaf-spotting disease.
The fungus has been found on diverse substrates: leaves, stems and roots of
plants; nematode cysts and human skin. It rarely causes human infections. Here we
report one case of subcutaneous phaeohyphomycosis caused by C. cassiicola with
prominent tissue necrosis in a woman. All of her clinical features pointed
towards a genetic linkage. Hence, whole-exome sequencing and Sanger sequencing
were performed on this patient. One mutation of CARD9 was detected.
PMID- 26440559
TI - Editorial Comment on "The Effect of Vortioxetine vs. Escitalopram on Sexual
Functioning in Adults with Well-Treated Major Depressive Disorder Experiencing
SSRI-Induced Sexual Dysfunction".
PMID- 26440560
TI - Rhodium-Catalyzed C-H Alkylation of Indolines with Allylic Alcohols: Direct
Access to beta-Aryl Carbonyl Compounds.
AB - The rhodium(III)-catalyzed site-selective C-H alkylation of various N
heterocycles, such as indolines, carbazoles, and pyrroles with readily available
allylic alcohols is described. This protocol allows the generation of a
heterocyclic scaffold containing a beta-aryl carbonyl moiety, which is known to
be a crucial structural unit of biologically active compounds.
PMID- 26440561
TI - The use of PCR-DGGE to determine bacterial fingerprints for poultry and red meat
abattoir effluent.
AB - Strict legislation and chemical composition monitoring of effluent may be useful,
but the data generated do not allow for source tracking, and enforcing
legislation remains problematic in the South African setting. These difficulties
emphasize the necessity for effluent source traceability. Denaturing gradient gel
electrophoresis (DGGE) targeting the V3 region of the 16S rRNA gene was
considered as fingerprinting technique for effluent originating from abattoirs
slaughtering different animal species. The influence of treatment to remove
excess fat from effluent prior to molecular analyses and different PCR approaches
on the detection of bacterial diversity were considered. Use of a treatment
option to remove fat and a nested PCR approach resulted in up to 51% difference
in inter-sample diversity similarity. A robust approach with no pre-treatment to
remove PCR inhibitors, such as fat, and direct amplification from genomic DNA
yielded optimal/maximal bacterial diversity fingerprints. Repeatable fingerprints
were obtained for poultry abattoir effluent over a 4-month period, but profiles
for the red meat abattoir varied with maximum similarity detected only 33.2%.
Genetic material from faecal indicators Aeromona spp and Clostridium spp were
detected. Genera unique to each effluent were present; Anoxybacillus,
Patulibacter and Oleispira in poultry abattoir effluent and Porphyromonas and
Peptostreptococcus in red meat abattoir effluent. SIGNIFICANCE AND IMPACT OF THE
STUDY: This study was the first to demonstrate the application of denaturing
gradient gel electrophoresis (DGGE) to construct bacterial diversity fingerprints
for high-throughput abattoir effluents. Proved redundancy of fat removal as PCR
inhibitor and change in diversity similarity introduced by nested PCR approach.
The importance of limiting excessive handling/processing which could lead to
misrepresented diversity profiles was emphasized.
PMID- 26440562
TI - Exploratory Study on the RNA-Binding Structural Motifs by Library Screening
Targeting pre-miRNA-29 a.
AB - The metabolic stream of microRNA (miRNA) production, the so-called maturation
process of miRNAs, became one of important metabolic paths for drug-targeting to
modulate the expression of genes related to a number of diseases. We carried out
discovery studies on small molecules binding to the precursor of miR-29a (pre-miR
29a) from a chemical library containing 41,119 compounds (AQ library) by the
fluorescent indicator displacement (FID) assay using the xanthone derivative
X2SdiMe as a fluorescent indicator. The FID assay provided 1075 compounds, which
showed an increase of fluorescence. These compounds were subsequently submitted
to a binding analysis in a surface plasmon resonance (SPR) assay on a pre-miR-29a
immobilized surface. 21 hit compounds were identified with a good reproducibility
in the binding. These compounds have not been reported to bind to RNA until now
and can be classified into two groups on the basis of the kinetics in the
binding. To gain more information on the motif structures that could be necessary
for the binding to pre-miR-29a, 19 substructures were selected from the hit
compounds. The substructure library (SS library) which consisted of 362 compounds
was prepared from the AQ library. An SPR assay of the SS library on pre-miR-29a
immobilized surface suggested that five substructures could potentially be
important structural motifs to bind to pre-miR-29a. These studies demonstrate
that the combination of FID-based screening of chemical library and subsequent
SPR assay would be one way for obtaining practical solutions for the discovery of
molecules which bind to the target pre-miRNAs.
PMID- 26440563
TI - Nonparallel Stacks of Donor and Acceptor Chromophores Evade Geminate Charge
Recombination.
AB - We report a nonparallel stacked arrangement of donor-acceptor (D-A) pairs for
prolonging the lifetime of photoinduced charge-separated states. Hydrogen
hydrogen steric repulsion in naphthalimide-naphthalene (NIN) dyad destabilizes
the planar geometry between the constituent units in solution/ground state.
Sterically imposed nonplanar geometry of the dyad allows the access of
nonparallel arrangement of the donor and acceptor stacks having triclinic space
group in the crystalline state. Antiparallel trajectory of excitons in
nonparallel D-A stacks can result in lower probability of geminate charge
recombination, upon photoexcitation, thereby resulting in a long-lived charge
separated state. Upon photoexcitation of the NIN dyad, electron transfer from
naphthalene to the singlet excited state of naphthalimide moiety results in
radical ion pair intermediates that survive >10,000-fold longer in the aggregated
state (taucra > 1.2 ns) as compared to that of monomeric dyad (taucrm < 110 fs),
monitored using femtosecond transient absorption spectroscopy.
PMID- 26440564
TI - Liver metabolic activity changes over time with neoadjuvant therapy in locally
advanced rectal cancer.
AB - OBJECTIVE: The aim of this study was to evaluate, using PET/computed tomography
(CT), changes in liver metabolic activity in patients with locally advanced
rectal cancer (LARC) after neoadjuvant chemoradiotherapy (CRT). PATIENTS AND
METHODS: A total of 29 biopsy-proven LARC patients between 2009 and 2012 were
studied. Liver standardized uptake values (SUVs) and SUVs adjusted for lean body
mass (SULs) were obtained from PET/CT images obtained at 1 h (early) and 2 h
(late) after (18)F-fluorodeoxyglucose ((18)F-FDG) administration both before and
after neoadjuvant CRT. Age, sex, BMI, lean body mass, blood glucose level, and
(18)F-FDG dose, which can influence liver SUVs and SULs, were also analyzed.
RESULTS: Fourteen (48%) men and 15 (52%) women with a mean age of 62+/-11 years
(range 34-80 years) were included in the study. The mean SUVs and SULs were
significantly decreased in the late scans. Sex was significantly correlated with
the mean liver SUV in early and late scans. The mean SUV differed significantly
between male and female patients in early and late images (P<0.05). In a
multivariate stepwise regression analysis, only liver SUVs (maximum and mean)
were significantly associated with BMI before and after therapy. SUVs were
significantly higher in the high (>=25) BMI group after but not before therapy.
Mean SUL was not influenced by BMI. CONCLUSION: Liver (18)F-FDG uptake is
consistent before and after neoadjuvant CRT therapy in patients with LARC. When
assessing response to therapy and using liver metabolic activity to indicate
background activity, BMI should be considered as it can influence liver metabolic
activity.
PMID- 26440565
TI - Evaluation of scatter limitation correction: a new method of correcting
photopenic artifacts caused by patient motion during whole-body PET/CT imaging.
AB - OBJECTIVE: Overcorrection of scatter caused by patient motion during whole-body
PET/computed tomography (CT) imaging can induce the appearance of photopenic
artifacts in the PET images. The present study aimed to quantify the accuracy of
scatter limitation correction (SLC) for eliminating photopenic artifacts.
METHODS: This study analyzed photopenic artifacts in (18)F-fluorodeoxyglucose
((18)F-FDG) PET/CT images acquired from 12 patients and from a National
Electrical Manufacturers Association phantom with two peripheral plastic bottles
that simulated the human body and arms, respectively. The phantom comprised a
sphere (diameter, 10 or 37 mm) containing fluorine-18 solutions with target-to
background ratios of 2, 4, and 8. The plastic bottles were moved 10 cm
posteriorly between CT and PET acquisitions. All PET data were reconstructed
using model-based scatter correction (SC), no scatter correction (NSC), and SLC,
and the presence or absence of artifacts on the PET images was visually
evaluated. The SC and SLC images were also semiquantitatively evaluated using
standardized uptake values (SUVs). RESULTS: Photopenic artifacts were not
recognizable in any NSC and SLC image from all 12 patients in the clinical study.
The SUVmax of mismatched SLC PET/CT images were almost equal to those of matched
SC and SLC PET/CT images. Applying NSC and SLC substantially eliminated the
photopenic artifacts on SC PET images in the phantom study. SLC improved the
activity concentration of the sphere for all target-to-background ratios. The
highest %errors of the 10 and 37-mm spheres were 93.3 and 58.3%, respectively,
for mismatched SC, and 73.2 and 22.0%, respectively, for mismatched SLC.
CONCLUSION: Photopenic artifacts caused by SC error induced by CT and PET image
misalignment were corrected using SLC, indicating that this method is useful and
practical for clinical qualitative and quantitative PET/CT assessment.
PMID- 26440566
TI - Characterization of 'cold' vertebrae on 18F-FDG PET/CT.
AB - INTRODUCTION: A photon-deficient ('cold') vertebra on fluorine-18
fluorodeoxyglucose (F-FDG) PET is a known entity and can arise as a result of
varying etiologies. A proper interpretation of this observation is required to
make an accurate diagnosis for appropriate management. METHODS: Twelve cases with
'cold' vertebrae on F-FDG PET/computed tomography (CT) were selected and analyzed
from a population of 600 patients with a known malignancy who had undergone whole
body F-FDG PET/CT for staging, disease viability assessment, response to
treatment, or suspected recurrence purposes. The patterns were studied and
correlated with clinical history and the results of the low-dose CT performed
with the PET scan for attenuation correction and anatomical localization.
RESULTS: The most common cause for cold vertebrae was found to be postexternal
radiotherapy, causing photopenia involving multiple vertebrae corresponding to
the radiotherapy portals. Two other causes found in the study were the
destruction of the vertebral marrow cavity by metastatic tumor cells and
vertebral hemangioma. Characteristic features of 'cold' vertebrae have been
described in the study with illustrations. CONCLUSION: Pattern recognition
coupled with clinical history and CT correlation of 'cold' vertebrae on F-FDG
PET/CT can help in diagnosing the correct underlying etiology, which can help in
better management of the patients.
PMID- 26440567
TI - Variety in bone marrow 18F-FDG uptake in Hodgkin lymphoma patients without
lymphomatous bone marrow involvement: does it have an explanation?
AB - OBJECTIVE: To directly correlate fluorine-18 fluoro-2-deoxy-D-glucose (F-FDG)
uptake of the iliac crest, as determined with PET, with both spatially matched
histological bone marrow parameters and laboratory markers in Hodgkin lymphoma
patients without lymphomatous bone marrow involvement at bone marrow biopsy.
MATERIALS AND METHODS: This retrospective study included 21 patients with newly
diagnosed Hodgkin lymphoma who underwent F-FDG-PET and who had a lymphoma
negative bone marrow biopsy of the right posterior iliac crest. F-FDG-PET maximum
standardized uptake value (SUVmax) was measured in the right posterior iliac
crest and correlated to histological bone marrow parameters (cellularity,
myeloid/erythroid ratio, degree of fibrosis, and reactive T- and B-lymphocytes)
and laboratory markers (hemoglobin, C-reactive protein lactate dehydrogenase, and
leukocyte and thrombocyte counts) using Pearson's correlation coefficient (R) for
Gaussian data or Kendall's tau (tau) for non-Gaussian data. RESULTS: There was a
significant moderate correlation between F-FDG-PET SUVmax and cellularity of the
iliac crest (R=0.519, P=0.016). Furthermore, there was a significant strong
inverse correlation between F-FDG-PET SUVmax of the iliac crest and hemoglobin
level (R=-0.661, P=0.001) and there was a significant moderate correlation
between F-FDG-PET SUVmax of the iliac crest and C-reactive protein level
(tau=0.441, P=0.007). All other correlations, including F-FDG-PET SUVmax of the
right iliac crest versus reactive T- and B-lymphocytes in the bone marrow, were
not significant. CONCLUSION: The observations suggest increased bone marrow F-FDG
uptake to be caused by red marrow hyperplasia because of anemia in Hodgkin
lymphoma. Increased bone marrow F-FDG uptake is unlikely to be caused by
inflammatory bone marrow changes.
PMID- 26440568
TI - Comparison of WHO, RECIST 1.1, EORTC, and PERCIST criteria in the evaluation of
treatment response in malignant solid tumors.
AB - AIM: To compare response assessment according to the WHO, RECIST 1.1, EORTC, and
PERCIST criteria in patients diagnosed with malignant solid tumors and who had
received cytotoxic chemotherapy to establish the strength of agreement between
each criterion. MATERIALS AND METHODS: Sixty patients with malignant solid tumors
were included in this retrospective study. The baseline and the sequential follow
up fluorine-18-fluorodeoxyglucose PET/computed tomography (CT) of each patient
were evaluated according to the WHO, RECIST 1.1, EORTC, and PERCIST criteria.
PET/CT images were used for both metabolic and anatomic evaluation. The
concurrent diagnostic CT and MRI images (performed within 1 week of PET/CT) were
also utilized when needed. The results were compared using the kappa-statistics.
RESULTS: The response and progression rates according to the WHO criteria were 37
and 38%, respectively. The same ratios were also found for RECIST 1.1 (kappa=1).
The response and progression rates according to the EORTC criteria were 47 and
40%, respectively. When PERCIST criteria were used, one patient with progressive
disease was upgraded to stable disease (kappa=0.976). As we found the same
results with WHO and RECIST 1.1 criteria, we used WHO criteria to compare the
anatomic and metabolic criteria. When we compared the WHO and EORTC criteria,
there was an agreement in 80% of the patients (kappa=0.711). With WHO and PERCIST
criteria, there was an agreement in 81.6% of the patients (kappa=0.736).
CONCLUSION: Significant agreement was detected when the WHO, RECIST 1.1, EORTC,
and PERCIST criteria were compared both within as well as between each other.
PMID- 26440569
TI - Quantitative analysis of basal and interim PET/CT images for predicting tumor
recurrence in patients with Hodgkin's lymphoma.
AB - OBJECTIVES: The qualitative analysis of interim PET has been reported to be
useful for predicting the outcome of Hodgkin's lymphoma (HL) after chemotherapy.
As the next step, our study aims to present a quantitative analysis on the basis
of both a basal (PET/CT0) and an interim (PET/CT2) scan to improve the prognostic
value of imaging in HL patients. PATIENTS AND METHODS: A cohort of 68 patients
undergoing a basal and an interim scan with F-fluorodeoxyglucose after two cycles
of chemotherapy consisting of adriamycin, bleomycin, vinblastine, and dacarbazine
were examined. Two subsets of patients with a positive and a negative interim
scan were selected. RESULTS: In patients with a negative scan, a total of 108
lymph node lesions showing a good response to chemotherapy were contoured,
whereas in the remaining patients with positive scans, six responder and 12
relapsing lymph node lesions were contoured. Standardized uptake value (SUV) and
Hounsfield unit (HU) values were included in the volumes contoured on
coregistered basal and interim scans and included in a database. A linear
regression model was used to identify the predictor of relapse at the lesion
level. The support vector machine analysis and bootstrap approach were used to
determine the model capability. The predictive models were presented as nomograms
on the basis of basal or both basal and interim studies. SUV at the basal/interim
study and basal HU values were predictors of a poor prognosis. In particular, the
higher points were associated with lower values of SUV and HU at baseline and the
higher values of SUV at the interim study. Using the bootstrap and support vector
machine approach, the cut-off of the model increased up to 89%. CONCLUSION: The
novel tool enables estimation of the risk of tumor relapse after chemotherapy in
HL patients on the basis of basal and interim PET/CT scans including SUV and
densitometric information.
PMID- 26440570
TI - Evaluating the use of optimally respiratory gated 18F-FDG-PET in target volume
delineation and its influence on radiation doses to the organs at risk in non
small-cell lung cancer patients.
AB - OBJECTIVE: This radiotherapy planning study evaluated tumour delineation using
both optimally respiratory gated and nongated fluorine-18 fluorodeoxyglucose-PET
(F-FDG-PET). METHODS: For 22 non-small-cell lung tumours, both scans were used to
create the nongated and gated (g) gross tumour volumes (GTVg) together with the
accompanying clinical target volumes (CTV) and planning target volumes (PTV). The
size of the target volumes (TV) was evaluated and the accompanying radiotherapy
plans were created to study the radiation doses to the organs at risk (OAR).
RESULTS: The median volumes of GTVg, CTVg and PTVg were statistically
significantly smaller compared with the corresponding nongated volumes, resulting
in a median TV reduction of 0.5 cm (interquartile range 0.1-1.2), 1.5 cm (-0.2 to
7.0) and 2.3 cm (-0.5 to 11.3) for the GTVg, CTVg and PTVg, respectively. For the
OAR, only the percentage of lung (GTV included) receiving at least 35 Gy was
significantly smaller after gating, with a median difference in lung volume
receiving at least 35 Gy of 5.7 cm (interquartile range -0.8 to 30.50).
CONCLUSION: Compared with nongated F-FDG-PET, the TVs obtained with optimally
respiratory gated F-FDG-PET were significantly smaller, however, without a
clinically relevant difference in radiation dose to the OAR.
PMID- 26440572
TI - The potential value of volume-based quantitative PET parameters and increased
bone marrow uptake for the prediction of survival in patients with malignant
pleural mesothelioma.
AB - PURPOSE: The aim of this study was to investigate the relationship between volume
based quantitative PET parameters and survival in patients with malignant pleural
mesothelioma (MPM) and to evaluate the potential value of bone marrow (BM) uptake
in predicting prognosis. MATERIALS AND METHODS: We retrospectively reviewed the
data of 51 patients with MPM who underwent initial staging by fluorine-18
fluorodeoxyglucose (F-FDG) PET/computerized tomography (PET/CT). F-FDG-PET images
were visually and quantitatively re-evaluated and maximum standardized uptake
values (SUVmax), mean standardized uptake values (SUVmean), metabolic tumor
volume (MTV), total lesion glycolysis of primary tumors, and pleural thickening
were calculated. In addition, BM and liver uptakes were measured; also, the
degree of BM uptake was scored visually. BM/liver ratio and visual BM uptake
score were noted. The correlations between quantitative PET parameters, BM
uptake, and overall survival were analyzed. RESULTS: F-FDG-PET scans upstaged 6
(11.8%) of 51 patients because of detection of previously unknown distant
metastasis. On univariate analysis, advanced disease stage, high leukocyte count
(>=10*10/ml), pleural thickening greater than 13 mm, SUVmax, SUVmean, MTV, total
lesion glycolysis, BM/liver greater than 1.01, and visual score 1 and 2 were
negative prognostic factors (P<0.05). In multivariate analysis, SUVmax greater
than 8.6 [P=0.027, hazard ratio (HR): 2.961], MTV greater than 112 (P=0.001, HR:
4.861), and visual score 2 (P=0.035, HR: 3.827) were associated independently
with a poor prognosis. CONCLUSION: The presence of distant metastasis is more
predictive of survival than PET nodal status in MPM patients. PET/CT has the
potential to provide prognostic information in MPM patients and there was a good
correlation between overall survival and volume-based PET parameters.
Determination of BM uptake may contribute toward the prediction of patient
outcome with other quantitative PET parameters.
PMID- 26440571
TI - Correlation between early 18F-FDG PET/CT response to BRAF and MEK inhibition and
survival in patients with BRAF-mutant metastatic melanoma.
AB - PURPOSE: Metabolic response to treatment measured by fluorine-18
fluorodeoxyglucose ((18)F-FDG) PET has prognostic implications in many cancers.
This study investigated the association between survival and early changes on
(18)F-FDG PET/computed tomography (CT) for patients with BRAF-mutant melanoma
receiving combined BRAF and MEK inhibition therapy. MATERIALS AND METHODS:
Overall, 24 patients with advanced BRAF-mutant melanoma were included. Patients
were treated with a BRAF inhibitor (vemurafenib or dabrafenib) and a MEK
inhibitor (cobimetinib or trametinib), and were imaged at baseline and shortly
thereafter with (18)F-FDG PET/CT. Each scan yielded two values of maximum
standardized uptake value (SUVmax): one for the most metabolically active focus
and one for the least responsive focus. Short-term treatment response was
assessed by evaluating the target lesions using the EROTC criteria. A Cox
proportional hazards model was used to examine associations between overall
survival (OS) and progression-free survival (PFS) and changes in SUVmax. RESULTS:
The mean time to follow-up (18)F-FDG PET/CT was 26 days. At follow-up, two
patients achieved a complete response. For the most metabolically active focus,
22 patients showed a partial response. For the least responsive focus, 18
patients showed a partial response, two had stable disease, and two had
progressive disease.A total of 16 patients were alive at the end of the study.
For the most metabolically active tumor, no association was observed between
changes in SUVmax and OS (P=0.73) or PFS (P=0.17). For the least responsive
tumor, change in SUVmax was associated with PFS [hazard ratio (HR)=1.34, 95%
confidence interval (CI): 1.06-1.71, P=0.01], but not OS (P=0.52). The ECOG score
was associated with OS (HR=11.81, 95% CI: 1.42-97.60, P=0.02) and PFS (HR=24.72,
95% CI: 3.23-189.42, P=0.002). CONCLUSION: Change in SUVmax for the least
responsive tumor and baseline functional performance may be useful prognostic
indicators for PFS in patients with BRAF-mutant melanoma.
PMID- 26440573
TI - Abdominal aortic aneurysms and diabetes mellitus.
AB - There is accumulating evidence that risk profiles differ between coronary artery
disease and abdominal aortic aneurysms (AAAs). However, diabetes mellitus (DM)
appears to be negatively associated with AAA formation. The underlying mechanisms
for this negative relationship are far from defined, but may include: increased
arterial wall matrix formation via advanced glycation end products; suppression
of plasmin and reduction of levels and activity of matrix metalloproteinases
(MMP)-2 and 9; diminished aortic wall macrophage infiltration, elastolysis and
neovascularization. In addition, the effect of pharmacological agents used for
the treatment of patients with DM on AAA formation has been studied with rather
controversial results. Statins, angiotensin converting enzyme inhibitors,
angiotensin receptor blockers, fenofibrate, antibiotics and some hypoglycemic
agents are beginning to be appreciated for a potential modest protection from
AAAs, but further studies are needed.
PMID- 26440574
TI - Does Trauma Impair Self-Control? Differences in Delaying Gratification Between
Former Indentured Child Laborers and Nontraumatized Controls.
AB - Traumatic experiences may affect an individual's ability to exercise self
control, which is an essential characteristic for successfully managing life. As
a measure of self-control, we used the delay discounting paradigm, that is, the
extent to which a person devalues delayed gratification. The aim of this study
was to investigate the relationship between childhood trauma and delay
discounting using a control group design with elderly participants with a mean
age of 76.2 years. Swiss former indentured child laborers (n=103) who had been
exposed to trauma during their childhood were compared with nontraumatized
controls (n=50). The trauma exposure group showed a considerably higher
preference for immediate smaller rewards than the controls, indicating their
lower self-control. A hierarchical regression analysis revealed that a history of
abuse, current self-efficacy, and education were significantly associated with
delay discounting. Implications for future research are discussed.
PMID- 26440575
TI - Delineating the Role of Helical Intermediates in Natively Unfolded Polypeptide
Amyloid Assembly and Cytotoxicity.
AB - Amyloid deposition is a hallmark of many diseases, such as the Alzheimer's
disease. Numerous amyloidogenic proteins, including the islet amyloid polypeptide
(IAPP) associated with type II diabetes, are natively unfolded and need to
undergo conformational rearrangements allowing the formation of locally ordered
structure(s) to initiate self-assembly. Recent studies have indicated that the
formation of alpha-helical intermediates accelerates fibrillization, suggesting
that these species are on-pathway to amyloid assembly. By identifying an IAPP
derivative with a restricted conformational ensemble that co-assembles with IAPP,
we observed that helical species were off-pathway in homogenous environment and
in presence of lipid bilayers or glycosaminoglycans. Moreover, preventing helical
folding potentiated membrane perturbation and IAPP cytotoxicity, indicating that
stabilization of helical motif(s) is a promising strategy to prevent cell
degeneration associated with amyloidogenesis.
PMID- 26440576
TI - Progress in Synthesis of Highly Active and Stable Nickel-Based Catalysts for
Carbon Dioxide Reforming of Methane.
AB - In recent decades, rising anthropogenic greenhouse gas emissions (mainly CO2 and
CH4 ) have increased alarm due to escalating effects of global warming. The dry
carbon dioxide reforming of methane (DRM) reaction is a sustainable way to
utilize these notorious greenhouse gases. This paper presents a review of recent
progress in the development of nickel-based catalysts for the DRM reaction. The
enviable low cost and wide availability of nickel compared with noble metals is
the main reason for persistent research efforts in optimizing the synthesis of
nickel-based catalysts. Important catalyst features for the rational design of a
coke-resistant nickel-based nanocatalyst for the DRM reaction are also discussed.
In addition, several innovative developments based on salient features for the
stabilization of nickel nanocatalysts through various means (which include
functionalization with precursors, synthesis by plasma treatment,
stabilization/confinement on mesoporous/microporous/carbon supports, and the
formation of metal oxides) are highlighted. The final part of this review covers
major issues and proposed improvement strategies pertaining to the rational
design of nickel-based catalysts with high activity and stability for the DRM
reaction.
PMID- 26440577
TI - Characteristics and exacerbating factors of chronic low back pain in Parkinson's
disease.
AB - BACKGROUND: The aim of this study was to determine the exacerbating factors of
chronic low back pain (LBP) and strategic points against LBP in patients with
Parkinson's disease (PD). METHODS: Forty-four consecutive PD patients complaining
of LBP were included. Clinical characteristics of PD and LBP, spinal
musculoskeletal condition, and clinical health status were evaluated. RESULTS:
Patient age at PD and LBP onset was contiguous, and LBP time period was mainly
described as constant or upon waking up. Exacerbating factors of LBP included
modified Hoehn and Yahr stage and motor complications of PD, such as the wearing
off phenomenon and dyskinesia. Bone quality demonstrated osteopenia due to
elevated bone resorption, with vitamins K and D insufficiencies. Spinal alignment
demonstrated an increased sagittal vertical axis (120.2 +/- 65.4 mm) with
decreased lumbar lordosis (-24.0 +/- 20.6 degrees ) and lumbar range of motion
(28.7 +/- 10.2 degrees ), which were significantly related to severity of LBP and
quality of life assessments. CONCLUSIONS: This study demonstrated that
exacerbating factors of LBP include stage of motor function, motor complications
of PD and stooped posture with decreased lumbar lordosis and range of lumbar
movement. Therefore, control of PD, including motor complications, active
treatment for osteoporosis and therapeutic exercise, are important for treating
chronic LBP in patients with PD.
PMID- 26440578
TI - A minimum attention control law for ball catching.
AB - Digital implementations of control laws typically involve discretization with
respect to both time and space, and a control law that can achieve a task at
coarser levels of discretization can be said to require less control attention,
and also reduced implementation costs. One means of quantitatively capturing the
attention of a control law is to measure the rate of change of the control with
respect to changes in state and time. In this paper we present an attention
minimizing control law for ball catching and other target tracking tasks based on
Brockett's attention criterion. We first highlight the connections between this
attention criterion and some well-known principles from human motor control.
Under the assumption that the optimal control law is the sum of a linear time
varying feedback term and a time-varying feedforward term, we derive an LQR-based
minimum attention tracking control law that is stable, and obtained efficiently
via a finite-dimensional optimization over the symmetric positive-definite
matrices. Taking ball catching as our primary task, we perform numerical
experiments comparing the performance of the various control strategies examined
in the paper. Consistent with prevailing theories about human ball catching, our
results exhibit several familiar features, e.g., the transition from open-loop to
closed-loop control during the catching movement, and improved robustness to
spatiotemporal discretization. The presented control laws are applicable to more
general tracking problems that are subject to limited communication resources.
PMID- 26440579
TI - Driving mechanism and sources of groundwater nitrate contamination in the rapidly
urbanized region of south China.
AB - Nitrate contamination of groundwater has become an environmental problem of
widespread concern in China. We collected 899 groundwater samples from a rapidly
urbanized area, in order to identify the main sources and driving mechanisms of
groundwater nitrate contamination. The results showed that the land use has a
significant effect on groundwater nitrate concentration (P<0.001). Landfill
leakage was an important source of nitrate in groundwater in the PRD (Pearl River
Delta) region, since landfill yielded the highest nitrate concentration (38.14
mg/L) and the highest ratio of exceeded standard (42.50%). In this study, the
driving mechanism of groundwater nitrate contamination was determined to be urban
construction and the secondary and tertiary industrial development, and
population growth. This study revealed that domestic wastewater and industrial
wastewater were the main sources of groundwater nitrate pollution. Therefore, the
priority method for relieving groundwater nitrate contamination is to control the
random discharge of domestic and industrial wastewater in regions undergoing
rapid urbanization. Capsule abstract. The main driving mechanism of groundwater
nitrate contamination was determined to be urban construction and the secondary
and tertiary industrial development, and population growth.
PMID- 26440580
TI - The effects of gestational and chronic atrazine exposure on motor behaviors and
striatal dopamine in male Sprague-Dawley rats.
AB - This study sought to investigate the effects of environmentally relevant
gestational followed by continued chronic exposure to the herbicide, atrazine, on
motor function, cognition, and neurochemical indices of nigrostriatal dopamine
(DA) activity in male rats. Dams were treated with 100 MUg/kg atrazine, 10mg/kg
atrazine, or vehicle on gestational day 1 through postnatal day 21. Upon weaning,
male offspring continued daily vehicle or atrazine gavage treatments for an
additional six months. Subjects were tested in a series of behavioral assays, and
24h after the last treatment, tissue samples from the striatum were analyzed for
DA and 3,4-dihydroxyphenylacetic acid (DOPAC). At 10mg/kg, this herbicide was
found to produce modest disruptions in motor functioning, and at both dose levels
it significantly lowered striatal DA and DOPAC concentrations. These results
suggest that exposures to atrazine have the potential to disrupt nigrostriatal DA
neurons and behaviors associated with motor functioning.
PMID- 26440581
TI - Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke:
Potential roles of Akt activation and HO-1 induction.
AB - The natural product totarol, a phenolic diterpenoid and a major constituent
isolated from the sap of Podocarpus totara, has been reported to have a potent
antimicrobial activity. In this study, we determined whether totarol possessed an
additional neuroprotective activity in vitro and in vivo. We found that totarol
prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in
primary rat cerebellar granule neuronal cells and cerebral cortical neurons.
Totarol increased Akt and GSK-3beta phosphorylation, Nrf2 and heme oxygenase-1
(HO-1) protein expressions and suppressed oxidative stress by increasing GSH and
SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective
effect by suppressing the totarol-induced changes in HO-1 expression and the
activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol
increased GSH and SOD activities. In a model of acute cerebral ischemic injury in
Sprague-Dawley rats, produced by occlusion of the middle cerebral artery for 2h
followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct
volume and improved the neurological deficit. In this model, totarol increased HO
1 expression and the activities of GSH and SOD. These observations suggest that
totarol may be a novel activator of the Akt/HO-1 pathway protecting against
ischemic stroke through reduction of oxidative stress.
PMID- 26440582
TI - Ergonomics in hair restoration surgeons.
AB - BACKGROUND: Musculoskeletal disorders (MSDs) are potential sources of morbidity
in hair restoration surgeons (HRS). This is particularly true for those who
perform follicular unit extraction (FUE). OBJECTIVE: To describe the nature,
prevalence, and extent of ergonomic or work-related MSDs among HRS. METHODS &
MATERIALS: A survey regarding MSDs was e-mailed to 100 HRS. RESULTS: Thirty-eight
HRS completed the survey, the majority of which were male and between the ages of
50-69. Fifty percent of respondents reported musculoskeletal symptoms occurring
during or after hair restoration procedures. Reports of pain during and after
surgery were higher for FUE procedures than single strip excision procedures.
Pain/fatigue/discomfort persisted for longer following FUE procedures compared to
strip excision procedures. MSD symptoms also negatively impacted quality of life.
Although the majority of respondents felt that ergonomics was important, only 30%
use ergonomic support when performing FUE procedures. CONCLUSION: Hair
restoration surgeons should be aware of MSD symptoms and particularly when
performing FUE. Symptoms reported included pain, fatigue, and discomfort,
sometimes lasting several hours following surgery. More attention needs to be
paid to ergonomics during hair restoration procedures in order to improve the
quality of life of surgeons and ultimately prevent the development of MSDs.
PMID- 26440583
TI - Post-pacemaker T-wave Inversions: Cardiac Memory.
PMID- 26440584
TI - Survival rates of anterior composites in managing tooth wear: systematic review.
AB - The use of composite restorations for patients with tooth wear is considered as a
more conservative treatment option. The aim of this study was to systematically
review the literature investigating the survival rates of anterior composite
restorations when used in managing tooth wear in patients. PubMed and MEDLINE
(Ovid) databases were screened for studies from 1995 to 2015. Cross-referencing
was used to further identify articles. Article selection and data extraction were
performed in duplication. Languages were restricted to English. A quality
appraisal of included studies was carried out using the Strength of
Recommendation Taxonomy system. Six hundred and sixty-six articles were initially
identified from which eight articles were full-text reviewed. Six articles
involving five studies were selected for inclusion. Three studies were
prospective and two retrospective. Included studies involved placement of 772
direct and indirect anterior composite restorations in 100 patients with follow
up periods between 5 months and 10 years. The survival rates of anterior
composites were >90% and 50% at 2.5 and 5 years, respectively. Posterior
occlusion was re-established in 91% of patients within 18 months. Meta-analysis
could not be performed due to the heterogeneity of included studies. The
systematic review's overall strength of recommendation was graded B. There is
evidence to support the use of anterior composite restorations at an increased
vertical dimension of occlusion in the short/medium-term management of tooth
wear. Long-term reporting of outcomes remains limited. Further research is needed
with standardised study design, detailed reporting of outcomes and long-term
review.
PMID- 26440585
TI - Comparison of positron emission tomography diffusion-weighted imaging (PET/DWI)
registration quality in a PET/MR scanner: Zoomed DWI vs. Conventional DWI.
AB - PURPOSE: To compare zoomed diffusion-weighted imaging (z-DWI) with reduced field
of view (FOV) by spatially selective radiofrequency pulses and conventional echo
planar imaging (EPI) DWI (c-DWI) with regard to registration quality using
positron emission tomography / magnetic resonance (PET/MR) in patients with
malignant tumors. MATERIALS AND METHODS: Fludeoxyglucose (18(F) ) PET imaging, c
DWI, and z-DWI were conducted simultaneously in 21 patients with known or
suspected malignancy using a PET/MR system. A fusion image showing the largest
tumor area was generated for analysis. Registration accuracy between PET and DWI
was assessed based on the area of maximum overlap and central point displacement
of the tumor. EPI factor, echo time (TE), matching area, and displacement were
compared between c-DWI and z-DWI by paired t-test. Agreement of apparent
diffusion coefficient (ADC) acquired by the two sequences were also assessed with
linear regression s and Bland-Altman plot analysis. RESULTS: Thirty-two lesions
were detected on both PET and DWI (mean size 536.3 +/- 471.8 mm(2) ). At least
one lesion was found in all subjects. In all cases, EPI factor was smaller with z
DWI than c-DWI (43.1 +/- 15.6 vs. 62.0 +/- 10.0, P < 0.0001), and TE was also
shorter for z-DWI (53.6 +/- 3.6 msec vs. 65.2 +/- 3.6 msec, P < 0.0001).
Registration accuracy was better with z-DWI in 30 of 32 lesions (93.8%), and both
average matching area and central point displacement were significantly improved
(79.8 +/- 18.1% vs. 61.8 +/- 22.9%, P < 0.0001 and 3.92 +/- 2.69 mm vs. 7.51 +/-
4.07 mm, P < 0.0001). ADC values calculated with c-DWI and z-DWI showed good
agreement. CONCLUSION: Zoomed DWI reduces image distortion and provides better
registration accuracy with PET images.
PMID- 26440586
TI - Origin of Outstanding Stability in the Lithium Solid Electrolyte Materials:
Insights from Thermodynamic Analyses Based on First-Principles Calculations.
AB - First-principles calculations were performed to investigate the electrochemical
stability of lithium solid electrolyte materials in all-solid-state Li-ion
batteries. The common solid electrolytes were found to have a limited
electrochemical window. Our results suggest that the outstanding stability of the
solid electrolyte materials is not thermodynamically intrinsic but is originated
from kinetic stabilizations. The sluggish kinetics of the decomposition reactions
cause a high overpotential leading to a nominally wide electrochemical window
observed in many experiments. The decomposition products, similar to the solid
electrolyte-interphases, mitigate the extreme chemical potential from the
electrodes and protect the solid electrolyte from further decompositions. With
the aid of the first-principles calculations, we revealed the passivation
mechanism of these decomposition interphases and quantified the extensions of the
electrochemical window from the interphases. We also found that the artificial
coating layers applied at the solid electrolyte and electrode interfaces have a
similar effect of passivating the solid electrolyte. Our newly gained
understanding provided general principles for developing solid electrolyte
materials with enhanced stability and for engineering interfaces in all-solid
state Li-ion batteries.
PMID- 26440587
TI - Stereoretentive formylation of (S)-proline: new application of the self
regeneration of stereo-centres (SRS) principle via chelation to cobalt(III).
AB - In a Vilsmeier-Haack-type formylation reaction the alpha-(dihydroxymethyl)-(S)
prolinato complex (+)578-p-[Co(tren){(RC,SN)-Pro[CH(OH)2]O}]Cl2.2H2O (22) was
produced stereoselectively (85% ee) from the (S)-prolinato complex, (+)578-p
[Co(tren){(SC,SN)-ProO}]2(H3O)2(HOEt2)(O3SCF3)7 (18). Similar reaction of the (S)
alaninato complex, (-)578-p-[Co(tren)(S-AlaO)](H3O)(O3SCF3)3 (13), produced the
racemate, rac-p-[Co(tren)(Ala{CH(OH)2}O)]SO4.2H2O (17). The contrasting
stereochemical outcomes of the formylation reaction with 18versus13 were ascribed
to the stereogenic character of the coordinated sec. amine of the (S)-prolinate
chelate in 18, which serves to uphold a chiral environment during reaction,
whereas reaction intermediates derived from 13 lack this stereochemical feature.
The stereoselective formylation of (S)-proline, relying on coordination to an
inert metal centre, as conducted here, constitutes a novel application of the
concept of Self-Regeneration of Stereocentres (SRS). The alpha-(hydroxymethyl)
(S)-prolinato complex, (+)578-p-[Co(tren){(RC,SN)-Pro(CH2OH)O}]Cl2.2H2O (23)
resulted from borohydride reduction of 22. The molecular structures of (+)578-p
[Co(tren){(RC,SN)-Pro[CH(OH)2]O}]Cl2.2H2O (22), rac-p-[Co(tren)
(Ala{CH(OH)2}O)]I2.H2O (17) and (+)578-p-[Co(tren){(RC,SN)-Pro(CH2OH)O}]Cl2.2H2O
(23) were established by X-ray crystallography.
PMID- 26440588
TI - Lewis Acid Assisted Diels-Alder Reaction with Regio- and Stereoselectivity: Anti
1,4-Adducts with Rigid Scaffolds and Their Application in Explosives Sensing.
AB - Unusual anti-1,4-adducts of anthracene derivatives and anti-adducts of inert
arenes with rigid scaffolds have been obtained via AlCl3-assisted Diels-Alder
reaction in good to excellent yields under mild conditions. Further derivation of
1,4-adducts gave pi-conjugated polymers which could act as sensors of explosive
species. This highly efficient synthesis method provides versatile approaches to
solid-state emissive pi-conjugated polymers.
PMID- 26440589
TI - The brain at risk: the sepsis syndrome and lessons from preclinical experiments.
AB - There is a growing awareness of the chronic brain injury that results from the
sepsis syndrome. We review experiments in several animal models of sepsis and
show in one model, cecal ligation and puncture (CLP), that permanent structural
pathology matures after the initial event. Specifically, we observed after
exposure to CLP significant decreased spine density on the apical tree, but not
the basal tree, of dendrites in the CA1 region of the dorsal hippocampus that was
accompanied by a significantly diminished arbor of the apical dendrites, by 8
weeks, but not after 2 weeks. These novel data from dendritic arborizations
elaborate information about a cohort of mice that had behaved in spatial memory
tasks. These results raise questions about the relationship between long-term
behavioral consequences and intervention strategies.
PMID- 26440590
TI - Upregulation of long noncoding RNA TMEVPG1 enhances T helper type 1 cell response
in patients with Sjogren syndrome.
AB - Long noncoding RNAs (lncRNA) play key roles in regulating autoimmunity and
immunity balance. LncRNA TMEVPG1, which is encoded by a gene located near the Ifn
gene, contributes to interferon gamma expression. We investigated the expression
of TMEVPG1 in patients with Sjogren syndrome (SS) to determine its role in the
pathogenesis of SS. In this study, we detected the relative expression of TMEVPG1
in CD4(+) T cells of 25 SS patients and 25 healthy donors. Moreover, the
proportion of Th1 cells and T-bet levels was also analyzed. Furthermore, we
explored the correlation between the expression of TMEVPG1 and the level of
autoantibodies, erythrocyte sedimentation rate (ESR) and IgG in SS patients. Our
results indicated that the proportion of Th1 cells and the levels of TMEVPG1 and
T-bet were increased in SS patients. In addition, the level of expression of
TMEVPG1 was correlated with the level of SSA, ESR and IgG. Our data suggest that
upregulation of lncRNA TMEVPG1 may be involved in the pathogenesis of Sjogren
syndrome.
PMID- 26440591
TI - Circulating T cell subsets are altered in individuals with chronic spinal cord
injury.
AB - Traumatic spinal cord injury (SCI) induces changes in the immune system, both
acutely and chronically. To better understand changes in the chronic phase of
SCI, we performed a prospective, observational study in a research institute and
Department of Physical Medicine and Rehabilitation of an academic medical center
to examine immune system parameters, including peripheral immune cell
populations, in individuals with chronic SCI as compared to uninjured
individuals. Here, we describe the relative frequencies of T cell populations in
individuals with chronic SCI as compared to uninjured individuals. We show that
the frequency of CD3+ and CD3+ CD4+ T cells are decreased in individuals with
chronic SCI, although activated (HLA-DR+) CD4+ T cells are elevated in chronic
SCI. We also examined regulatory T cells (Tregs), defined as CD3+ CD4+ CD25+
CD127lo and CCR4+, HLA-DR+ or CCR4+ HLA-DR+. To our knowledge, we provide the
first evidence that CCR4+, HLA-DR+ or CCR4+ HLA-DR+ Tregs are expanded in
individuals with SCI. These data support additional functional studies of T cells
isolated from individuals with chronic SCI, where alterations in T cell
homeostasis may contribute to immune dysfunction, such as immunity against
infections or the persistence of chronic inflammation.
PMID- 26440594
TI - Pitfalls of cleaning controls in ultrasonic washers.
PMID- 26440592
TI - Exploratory study for identifying systemic biomarkers that correlate with pain
response in patients with intervertebral disc disorders.
AB - Molecular events that drive disc damage and low back pain (LBP) may precede
clinical manifestation of disease onset and can cause detrimental long-term
effects such as disability. Biomarkers serve as objective molecular indicators of
pathological processes. The goal of this study is to identify systemic
biochemical factors as predictors of response to treatment of LBP with epidural
steroid injection (ESI). Since inflammation plays a pivotal role in LBP, this
pilot study investigates the effect of ESI on systemic levels of 48 inflammatory
biochemical factors (cytokines, chemokines, and growth factors) and examines the
relationship between biochemical factor levels and pain or disability in patients
with disc herniation (DH), or other diagnoses (Other Dx) leading to low back
pain, which included spinal stenosis (SS) and degenerative disc disease (DDD).
Study participants (n = 16) were recruited from a back pain management practice.
Pain numerical rating score (NRS), Oswestry Disability Index (ODI), and blood
samples were collected pre- and at 7 to 10 days post-treatment. Blood samples
were assayed for inflammatory mediators using commercial multiplex assays.
Mediator levels were compared pre- and post-treatment to investigate the
potential correlations between clinical and biochemical outcomes. Our results
indicate that a single ESI significantly decreased systemic levels of SCGF-beta
and IL-2. Improvement in pain in all subjects was correlated with changes in
chemokines (MCP-1, MIG), hematopoietic progenitor factors (SCGF-beta), and
factors that participate in angiogenesis/fibrosis (HGF), nociception (SCF, IFN
alpha2), and inflammation (IL-6, IL-10, IL-18, TRAIL). Levels of biochemical
mediators varied based on diagnosis of LBP, and changes in pain responses and
systemic mediators from pre- to post-treatment were dependent on the diagnosis
cohort. In the DH cohort, levels of IL-17 and VEGF significantly decreased post
treatment. In the Other Dx cohort, levels of IL-2Ralpha, IL-3, and SCGF-beta
significantly decreased post-treatment. In order to determine whether mediator
changes were related to pain, correlations between change in pain scores and
change in mediator levels were performed. Subjects with DH demonstrated a profile
signature that implicated hematopoiesis factors (SCGF-beta, GM-CSF) in pain
response, while subjects with Other Dx demonstrated a biomarker profile that
implicated chemokines (MCP-1, MIG) and angiogenic factors (HGF, VEGF) in pain
response. Our findings provide evidence that systemic biochemical factors in
patients with LBP vary by diagnosis, and pain response to treatment is associated
with a unique profile of biochemical responses in each diagnosis group. Future
hypothesis-based studies with larger subject cohorts are warranted to confirm the
findings of this pilot exploratory study.
PMID- 26440593
TI - Impact of rapid screening for discontinuation of methicillin-resistant
Staphylococcus aureus contact precautions.
AB - BACKGROUND: A history of methicillin-resistant Staphylococcus aureus (MRSA) is a
determinant of inpatient bed assignment. METHODS: We assessed outcomes associated
with rapid testing and discontinuation of MRSA contact precautions (CP) in a
prospective cohort study of polymerase chain reaction (PCR)-based screening in
the Emergency Department (ED) of Massachusetts General Hospital. Eligible
patients had a history of MRSA and were assessed and enrolled if documented off
antibiotics with activity against MRSA and screened for nasal colonization
(subject visit). PCR-negative subjects had CP discontinued; the primary outcome
was CP discontinuation. We identified semiprivate rooms in which a bed was vacant
owing to the CP status of the study subject, calculated the hours of vacancy, and
compared idle bed-hours by PCR results. Program costs were compared with
predicted revenue. RESULTS: There were 2864 eligible patients, and 648 (22.6%)
subject visits were enrolled. Of these, 65.1% (422/648) were PCR-negative and had
CP discontinued. PCR-negative subjects had fewer idle bed-hours compared with PCR
positive subjects (28.6 +/- 25.2 vs 75.3 +/- 70.5; P < .001). The expected
revenues from occupied idle beds and averted CP costs ranged from $214,160 to
$268,340, and exceeded the program costs. CONCLUSION: A program of targeted PCR
based screening for clearance of MRSA colonization resulted in expected revenues
and decreased CP costs that outweighed programmatic costs.
PMID- 26440595
TI - Physical function and activity among older adults in Jodhpur, India.
AB - BACKGROUND: Physical activity impacts the ageing process; yet, few studies have
examined relationships among physical activity, functional abilities and health
among older adults in non-Western settings. AIM: This study tests for
associations among measures of physical activity, function and self-report health
conditions among 200 older adults (49--50 years old) in Jodhpur, Rajasthan,
India. METHODS: Seven consecutive days of accelerometry data were used in
measures of physical activity (Total Daily Energy Expenditure [TDEE], Physical
Activity Level [PAL], Daily Average Activity Count [AC] and Activity Energy
Expenditure [AEE]). Measures of physical function included grip strength, timed
walk and daily average sit time. Participants reported if they had been diagnosed
with diabetes, hypertension, arthritis and/or depression. RESULTS: All four
measures of physical activity were positively associated with grip strength (p <=
0.05). AC was negatively associated with timed walk (p <= 0.05), and both AC and
AEE were negatively associated with daily average sit time (p <= 0.05). Women who
reported diagnosis of hypertension had lower PAL and AC (p <= 0.05). CONCLUSION:
This study provides further evidence for a positive relationship between physical
activity and functional ability among older adults and between physical activity
and cardiovascular health among women in India.
PMID- 26440596
TI - Histology-guided protein digestion/extraction from formalin-fixed and paraffin
embedded pressure ulcer biopsies.
AB - Herein we present a simple, reproducible and versatile approach for in situ
protein digestion and identification on formalin-fixed and paraffin-embedded
(FFPE) tissues. This adaptation is based on the use of an enzyme delivery
platform (hydrogel discs) that can be positioned on the surface of a tissue
section. By simultaneous deposition of multiple hydrogels over select regions of
interest within the same tissue section, multiple peptide extracts can be
obtained from discrete histological areas. After enzymatic digestion, the
hydrogel extracts are submitted for LC-MS/MS analysis followed by database
inquiry for protein identification. Further, imaging mass spectrometry (IMS) is
used to reveal the spatial distribution of the identified peptides within a
serial tissue section. Optimization was achieved using cutaneous tissue from
surgically excised pressure ulcers that were subdivided into two prime regions of
interest: the wound bed and the adjacent dermal area. The robust display of
tryptic peptides within these spectral analyses of histologically defined tissue
regions suggests that LC-MS/MS in combination with IMS can serve as useful
exploratory tools.
PMID- 26440597
TI - Use of a Human Artificial Chromosome for Delivering Trophic Factors in a Rodent
Model of Amyotrophic Lateral Sclerosis.
AB - A human artificial chromosome (HAC) is maintained as an episome within a cell and
avoids random integration into the host genome. It can transfer multiple and/or
large transgenes along with their regulatory elements thereby resembling native
chromosomes. Using this HAC system, we established mesenchymal stem cells (MSCs)
that simultaneously expressed hepatocyte growth factor, glial cell line-derived
neurotrophic factor, and insulin-like growth factor 1, termed HAC-MSCs. This cell
line provides an opportunity for stable transplantation and thorough analyses. We
then introduced the cells for the treatment of a neurodegenerative disorder,
amyotrophic lateral sclerosis. The HAC-MSCs were transplanted via the fourth
cerebral ventricle (CV) or intravenous (i.v.) infusion at various ages of
recipient mice. Littermate- and sex-matched mice underwent a sham procedure.
Compared to the controls, there was an encouraging trend of increased life span
via CV transplantation and delayed onset in i.v. infusion 60 days after
transplantation. Further, we confirmed a statistically significant increase in
life span via CV transplantation at 100 days. This effect was not seen in mice
transplanted with MSCs lacking the HAC. We successfully enhanced the trophic
potential of the MSCs using the HAC. This strategy could be a promising direction
for the treatment of neurodegenerative disorders.
PMID- 26440598
TI - Pharmacokinetics of a Cholesterol-conjugated Aptamer Against the Hepatitis C
Virus (HCV) NS5B Protein.
AB - Hepatitis C virus (HCV) is the major cause of progressive liver disease such as
chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Previously, we
reported that a 29 nucleotide-long 2'-F pyrimidine modified RNA aptamer against
the HCV nonstructural protein 5B efficiently inhibited HCV replication and
suppressed HCV infectious virus particle formation in a cell culture system. In
this study, we modified this aptamer through conjugation of cholesterol for in
vivo availability. This cholesterol-conjugated aptamer (chol-aptamer) efficiently
entered the cell and inhibited HCV RNA replication, without any alteration in
gene expression profiling including innate immune response-related genes.
Moreover, systemic administration of the chol-aptamer was well tolerated without
any abnormalities in mice. To evaluate the pharmacokinetics of the chol-aptamer
in vivo, dose proportionality, bioavailability, and pharmacokinetic parameters
were evaluated by noncompartmental analyses in normal BALB/c mice. Population
analysis was performed using nonlinear mixed effects modeling. Moreover, the
pharmacokinetics of two different routes (intravenous, IV, versus
intraperitoneal, IP) were compared. Cholesterol conjugation showed dose
proportionality, extended the time that the aptamer was in the plasma, and
enhanced aptamer exposure to the body. Noticeably, the IV route was more suitable
than the IP route due to the chol-aptamer remaining in the plasma for a longer
period of time.
PMID- 26440599
TI - Peptide Nucleic Acid Promotes Systemic Dystrophin Expression and Functional
Rescue in Dystrophin-deficient mdx Mice.
AB - Antisense oligonucleotide (AO)-mediated exon-skipping therapeutics shows great
promise for Duchenne muscular dystrophy (DMD) patients. However, recent failure
with drisapersen, an AO candidate drug in phase 3 trial, highlights the
importance of exploring other effective AO chemistries for DMD. Previously, we
demonstrated the appreciable biological activity of peptide nucleic acid (PNA)
AOs in restoring dystrophin expression in dystrophin-deficient mdx mice
intramuscularly. Here, we further explore the systemic potential and feasibility
of PNA AOs in mediating exon skipping in mdx mice as a comprehensive systemic
evaluation remains lacking. Systemic delivery of PNA AOs resulted in therapeutic
level of dystrophin expression in body-wide peripheral muscles and improved
dystrophic pathology in mdx mice without any detectable toxicity. Up to 40% of
dystrophin restoration was achieved in gastrocnemius, to a less extent with other
skeletal muscles, with no dystrophin in heart. Notably, comparable systemic
activity was obtained between PNA AOs and phosphorodiamidate morpholino oligomer,
a DMD AO chemistry in phase 3 clinical trial, under an identical dosing regimen.
Overall, our data demonstrate that PNA is viable for DMD exon-skipping
therapeutics with 20 mer showing the best combination of activity, solubility,
and safety and further modifications to increase PNA aqueous solubility can
enable longer, more effective therapeutics without the associated toxicity.
PMID- 26440601
TI - Atom-economical synthesis of a high silica CHA zeolite using a solvent-free
route.
AB - A high silica CHA zeolite is successfully synthesized in the presence of a small
amount of N,N,N-dimethylethylcyclohexylammonium bromide under solvent-free
conditions. Catalytic tests for the selective catalytic reduction of NOx with NH3
(NH3-SCR) and methanol-to-olefins (MTO) show that the sample from the solvent
free route exhibits comparable catalytic properties to that from the conventional
route.
PMID- 26440600
TI - Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug
Targets for Alzheimer's Disease.
AB - Alzheimer's disease (AD) is a multifactorial, fatal neurodegenerative disorder
characterized by the abnormal accumulation of Abeta and Tau deposits in the
brain. There is no cure for AD, and failure at different clinical trials
emphasizes the need for new treatments. In recent years, significant progress has
been made toward the development of miRNA-based therapeutics for human disorders.
This study was designed to evaluate the efficiency and potential safety of miRNA
replacement therapy in AD, using miR-15/107 paralogues as candidate drug targets.
We identified miR-16 as a potent inhibitor of amyloid precursor protein (APP) and
BACE1 expression, Abeta peptide production, and Tau phosphorylation in cells.
Brain delivery of miR-16 mimics in mice resulted in a reduction of AD-related
genes APP, BACE1, and Tau in a region-dependent manner. We further identified
Nicastrin, a gamma-secretase component involved in Abeta generation, as a target
of miR-16. Proteomics analysis identified a number of additional putative miR-16
targets in vivo, including alpha-Synuclein and Transferrin receptor 1. Top
ranking biological networks associated with miR-16 delivery included AD and
oxidative stress. Collectively, our data suggest that miR-16 is a good candidate
for future drug development by targeting simultaneously endogenous regulators of
AD biomarkers (i.e., Abeta and Tau), inflammation, and oxidative stress.
PMID- 26440602
TI - Guidelines for Conducting a Victim-Sensitive Interview.
AB - Victim sensitive interviews allow the adult investigator to gather vital facts
from a child. Within these interviews, the investigator is provided with an
opportunity to elicit responses from the child regarding allegations that have
taken place. These allegations often have many origins and may involve sexual
impropriety, abuse, taunting, and torture of a physical nature, verbal nature, or
both. The purpose of this article is to provide standardized guidelines that can
assist individuals from various occupational fields in conducting victim
sensitive interviews. The standardized guidelines provided offer an assemblage of
general principles that have consistently appeared within literature as well as
in manuals provided by various jurisdictions. These guidelines refer to a
practice of conduct that is recommended; however, variance with implementation is
allowed. It is assumed that the reader brings a level of clinical experience to
the material provided in this article.
PMID- 26440603
TI - Drug-Induced Diabetes Mellitus: Evidence for Statins and Other Drugs Affecting
Glucose Metabolism.
AB - Abnormalities of glucose metabolism and glucose tolerance, either because of a
reduction in tissue sensitivity to insulin (e.g., in liver, skeletal muscle, and
adipose tissues) and/or a reduction in pancreatic insulin secretion, are
associated with a number of unwanted health outcomes. Even small increases in
circulating glucose levels (often described as dysglycemia or prediabetes) may
confer an increased risk of cardiovascular (CV) disease and progression to overt
type 2 diabetes. A number of drug therapies, many of them used long term in
chronic disease management, have adverse effects on glucose metabolism, diabetes
risk, and glycemic control among patients with preexisting diabetes. In this
study, we review the evidence, underlying mechanisms, and the clinical
significance of drug-related adverse effects on glucose metabolism.
PMID- 26440605
TI - Interactions Between the Prefrontal Cortex and Attentional Systems During
Volitional Affective Regulation: An Effective Connectivity Reappraisal Study.
AB - Reappraisal is an emotion regulation strategy used to change reactions to emotion
related stimuli by reinterpreting their meaning. During down-regulation of
negative emotions, wide areas of the prefrontal cortex (PFC) inhibit emotion
related brain areas such as the amygdala. Little is known, however, about how
this control activity influences the earliest stages of affective responses by
modulating perceptual and attentional areas. The aim of this study is to identify
the connectivity patterns between the PFC and the core regions of two well-known
attentional networks: the dorsal attentional network (which controls attention
volitionally) and the ventral attentional network (which controls attention
spontaneously) during reappraisal. We used a novel method to study emotional
control processes: the directed transfer function, an autoregressive effective
connectivity method based on Granger causality. It was applied to EEG recordings
to quantify the direction and intensity of information flow during passively
watching (control condition) or reappraising (experimental condition) negative
film clips. Reappraisal was mostly associated with increased top-down influences
from the right dorsolateral PFC over attentional and perceptual areas, reaching
areas including dorsal attentional regions. The left dorsolateral PFC was
associated with the activation of the ventral attentional network. Passively
watching clips (control condition) resulted in increased flow from attentional
areas to the left dorsolateral PFC, what is interpreted as a monitoring process.
Thus, reappraisal seems to be related to both volitional and automatic control of
attention, triggered by the right and left dorsolateral PFC respectively.
PMID- 26440604
TI - Transcranial magnetic stimulation facilitates neurorehabilitation after pediatric
traumatic brain injury.
AB - Traumatic brain injury (TBI) is the leading cause of death and disability among
children in the United States. Affected children will often suffer from
emotional, cognitive and neurological impairments throughout life. In the
controlled cortical impact (CCI) animal model of pediatric TBI (postnatal day 16
17) it was demonstrated that injury results in abnormal neuronal hypoactivity in
the non-injured primary somatosensory cortex (S1). It materializes that reshaping
the abnormal post-injury neuronal activity may provide a suitable strategy to
augment rehabilitation. We tested whether high-frequency, non-invasive
transcranial magnetic stimulation (TMS) delivered twice a week over a four-week
period can rescue the neuronal activity and improve the long-term functional
neurophysiological and behavioral outcome in the pediatric CCI model. The results
show that TBI rats subjected to TMS therapy showed significant increases in the
evoked-fMRI cortical responses (189%), evoked synaptic activity (46%), evoked
neuronal firing (200%) and increases expression of cellular markers of
neuroplasticity in the non-injured S1 compared to TBI rats that did not receive
therapy. Notably, these rats showed less hyperactivity in behavioral tests. These
results implicate TMS as a promising approach for reversing the adverse neuronal
mechanisms activated post-TBI. Importantly, this intervention could readily be
translated to human studies.
PMID- 26440606
TI - The Effect of Age Correction on Multivariate Classification in Alzheimer's
Disease, with a Focus on the Characteristics of Incorrectly and Correctly
Classified Subjects.
AB - The similarity of atrophy patterns in Alzheimer's disease (AD) and in normal
aging suggests age as a confounding factor in multivariate models that use
structural magnetic resonance imaging (MRI) data. To study the effect and compare
different age correction approaches on AD diagnosis and prediction of mild
cognitive impairment (MCI) progression as well as investigate the characteristics
of correctly and incorrectly classified subjects. Data from two multi-center
cohorts were included in the study [AD = 297, MCI = 445, controls (CTL) = 340].
34 cortical thickness and 21 subcortical volumetric measures were extracted from
MRI. The age correction approaches involved: using age as a covariate to MRI
derived measures and linear detrending of age-related changes based on CTL
measures. Orthogonal projections to latent structures was used to discriminate
between AD and CTL subjects, and to predict MCI progression to AD, up to 36
months follow-up. Both age correction approaches improved models' quality in
terms of goodness of fit and goodness of prediction, as well as classification
and prediction accuracies. The observed age associations in classification and
prediction results were effectively eliminated after age correction. A detailed
analysis of correctly and incorrectly classified subjects highlighted age
associations in other factors: ApoE genotype, global cognitive impairment and
gender. The two methods for age correction gave similar results and show that age
can partially masks the influence of other aspects such as cognitive impairment,
ApoE-e4 genotype and gender. Age-related brain atrophy may have a more important
association with these factors than previously believed.
PMID- 26440608
TI - Practice standards for emergency nursing: An international review.
AB - BACKGROUND: Presentations to emergency departments (EDs) and patient acuity
continue to increase. Whilst strategies to deliver safe patient care in the ED
are evolving, emergency nurses need to be well educated through specialist
qualifications to enable delivery of advanced patient care. This paper presents a
comparative analysis of available international practice and competency standards
for nurses graduating from emergency nursing courses in Australia, Canada, New
Zealand, the United Kingdom, and the United States. METHODS: CINAHL, Scopus, Ovid
MEDLINE, and Embase were searched for papers, published in English, using the
terms: 'emergency', 'accident and emergency', 'nursing', 'competency', 'practice
standards', 'scope of practice', 'regulation', and 'specialist standards'.
Secondary sources from relevant reference lists and professional websites were
also searched. RESULTS: The standards from the five countries were common across
five domains: clinical expertise, communication, teamwork, resources and
environment, and legal. None of the standards were specific to the emergency
nursing graduate, and there was variability in the level of expertise required
for which the standards apply. CONCLUSIONS: The available practice standards
demonstrated some commonality. Consideration of the utility of a universal
framework for informing the development of emergency nursing practice standards
and emergency nursing curriculum for nurses wishing to specialise is needed.
PMID- 26440607
TI - Derivation and validation of two decision instruments for selective chest CT in
blunt trauma: a multicenter prospective observational study (NEXUS Chest CT).
AB - BACKGROUND: Unnecessary diagnostic imaging leads to higher costs, longer
emergency department stays, and increased patient exposure to ionizing radiation.
We sought to prospectively derive and validate two decision instruments (DIs) for
selective chest computed tomography (CT) in adult blunt trauma patients. METHODS
AND FINDINGS: From September 2011 to May 2014, we prospectively enrolled blunt
trauma patients over 14 y of age presenting to eight US, urban level 1 trauma
centers in this observational study. During the derivation phase, physicians
recorded the presence or absence of 14 clinical criteria before viewing chest
imaging results. We determined injury outcomes by CT radiology readings and
categorized injuries as major or minor according to an expert-panel-derived
clinical classification scheme. We then employed recursive partitioning to derive
two DIs: Chest CT-All maximized sensitivity for all injuries, and Chest CT-Major
maximized sensitivity for only major thoracic injuries (while increasing
specificity). In the validation phase, we employed similar methodology to
prospectively test the performance of both DIs. We enrolled 11,477 patients-6,002
patients in the derivation phase and 5,475 patients in the validation phase. The
derived Chest CT-All DI consisted of (1) abnormal chest X-ray, (2) rapid
deceleration mechanism, (3) distracting injury, (4) chest wall tenderness, (5)
sternal tenderness, (6) thoracic spine tenderness, and (7) scapular tenderness.
The Chest CT-Major DI had the same criteria without rapid deceleration mechanism.
In the validation phase, Chest CT-All had a sensitivity of 99.2% (95% CI 95.4%
100%), a specificity of 20.8% (95% CI 19.2%-22.4%), and a negative predictive
value (NPV) of 99.8% (95% CI 98.9%-100%) for major injury, and a sensitivity of
95.4% (95% CI 93.6%-96.9%), a specificity of 25.5% (95% CI 23.5%-27.5%), and a
NPV of 93.9% (95% CI 91.5%-95.8%) for either major or minor injury. Chest CT
Major had a sensitivity of 99.2% (95% CI 95.4%-100%), a specificity of 31.7% (95%
CI 29.9%-33.5%), and a NPV of 99.9% (95% CI 99.3%-100%) for major injury and a
sensitivity of 90.7% (95% CI 88.3%-92.8%), a specificity of 37.9% (95% CI 35.8%
40.1%), and a NPV of 91.8% (95% CI 89.7%-93.6%) for either major or minor injury.
Regarding the limitations of our work, some clinicians may disagree with our
injury classification and sensitivity thresholds for injury detection.
CONCLUSIONS: We prospectively derived and validated two DIs (Chest CT-All and
Chest CT-Major) that identify blunt trauma patients with clinically significant
thoracic injuries with high sensitivity, allowing for a safe reduction of
approximately 25%-37% of unnecessary chest CTs. Trauma evaluation protocols that
incorporate these DIs may decrease unnecessary costs and radiation exposure in
the disproportionately young trauma population.
PMID- 26440609
TI - No evidence of risk-taking or impulsive behaviour in a person with episodic
amnesia: Implications for the role of the hippocampus in future-regarding
decision-making.
AB - Does advantageous decision-making require one to explicitly remember the outcome
of a series of past decisions or to imagine future personal consequences of one's
choices? Findings that amnesic people with hippocampal damage cannot form a clear
preference for advantageous decks over many learning trials on the Iowa Gambling
Task (IGT) have been taken to suggest that complex decision-making on the IGT
depends on declarative (episodic) memory and hippocampal integrity.
Alternatively, impaired IGT performance in amnesic individuals could be secondary
to risk-taking and/or impulsive behaviour resulting from impaired episodic future
thinking (i.e. prospection) known to accompany amnesia. We tested this
possibility in the amnesic individual K.C. using the IGT and the Toronto Gambling
Task (TGT), a novel task that dissociates impulsivity from risk-taking without
placing demands on declarative memory. K.C. did not develop a preference for
advantageous over disadvantageous decks on the IGT and, instead, showed a slight
preference for short-term gains and an inability to acquire a more adaptive
appreciation of longer-term losses. He also did not display impulsive or risk
taking behaviour on the TGT, despite a profound inability to imagine personal
future experiences. These findings suggest that impaired decision-making on the
IGT in amnesia is unlikely to reflect a predilection to act in the moment or
failure to take future consequences into account. Instead, some forms of future
regarding decision-making may be dissociable, with performance on tasks relying
on declarative learning or on episodic-constructive processes more likely to be
impaired.
PMID- 26440610
TI - Overt Social Support Behaviors: Associations With PTSD, Concurrent Depressive
Symptoms and Gender.
AB - Women are twice as likely as men to develop a posttraumatic stress disorder
(PTSD). Gender differences in social support after a traumatic event might
partially explain this disparity. However, the portrait of the links among PTSD,
depression, social support, and gender is still unclear. This study examined
behaviors of individuals with PTSD and their significant other in relation to
PTSD and concurrent depressive symptoms, and tested gender as a moderator of
these associations. Observed overt supportive and countersupportive behaviors of
68 dyads composed of an individual with PTSD and a significant other in a trauma
oriented discussion were coded with a support coding system and analyzed
according to gender. Gender was revealed to act as a moderator of the links
between interactional behaviors of individuals with PTSD and their concurrent
depressive symptoms. More specifically, women were less implicated and less
likely to propose positive solutions compared with men. On the other hand, men
were more implicated and less likely to criticize their significant other than
were women. PTSD and concurrent depressive symptoms were related to poorer
interpersonal communication in women. Hence, women and men with PTSD and
concurrent depressive symptoms might benefit from gender-tailored interventions
targeting symptoms and dyadic behaviors.
PMID- 26440611
TI - Association between depressive symptoms, weight and treatment outcome in a very
large anorexia nervosa sample.
PMID- 26440612
TI - Evaluating Written Patient Information for Eczema in German: Comparing the
Reliability of Two Instruments, DISCERN and EQIP.
AB - Patients actively seek information about how to cope with their health problems,
but the quality of the information available varies. A number of instruments have
been developed to assess the quality of patient information, primarily though in
English. Little is known about the reliability of these instruments when applied
to patient information in German. The objective of our study was to investigate
and compare the reliability of two validated instruments, DISCERN and EQIP, in
order to determine which of these instruments is better suited for a further
study pertaining to the quality of information available to German patients with
eczema. Two independent raters evaluated a random sample of 20 informational
brochures in German. All the brochures addressed eczema as a disorder and/or
therapy options and care. Intra-rater and inter-rater reliability were assessed
by calculating intra-class correlation coefficients, agreement was tested with
weighted kappas, and the correlation of the raters' scores for each instrument
was measured with Pearson's correlation coefficient. DISCERN demonstrated
substantial intra- and inter-rater reliability. It also showed slightly better
agreement than EQIP. There was a strong correlation of the raters' scores for
both instruments. The findings of this study support the reliability of both
DISCERN and EQIP. However, based on the results of the inter-rater reliability,
agreement and correlation analyses, we consider DISCERN to be the more precise
tool for our project on patient information concerning the treatment and care of
eczema.
PMID- 26440613
TI - The Adaptor Protein Myd88 Is a Key Signaling Molecule in the Pathogenesis of
Irinotecan-Induced Intestinal Mucositis.
AB - Intestinal mucositis is a common side effect of irinotecan-based anticancer
regimens. Mucositis causes cell damage, bacterial/endotoxin translocation and
production of cytokines including IL-1 and IL-18. These molecules and toll-like
receptors (TLRs) activate a common signaling pathway that involves the Myeloid
Differentiation adaptor protein, MyD88, whose role in intestinal mucositis is
unknown. Then, we evaluated the involvement of TLRs and MyD88 in the pathogenesis
of irinotecan-induced intestinal mucositis. MyD88-, TLR2- or TLR9-knockout mice
and C57BL/6 (WT) mice were given either saline or irinotecan (75 mg/kg, i.p. for
4 days). On day 7, animal survival, diarrhea and bacteremia were assessed, and
following euthanasia, samples of the ileum were obtained for morphometric
analysis, myeloperoxidase (MPO) assay and measurement of pro-inflammatory
markers. Irinotecan reduced the animal survival (50%) and induced a pronounced
diarrhea, increased bacteremia, neutrophil accumulation in the intestinal tissue,
intestinal damage and more than twofold increased expression of MyD88 (200%),
TLR9 (400%), TRAF6 (236%), IL-1beta (405%), IL-18 (365%), COX-2 (2,777%) and NF
kappaB (245%) in the WT animals when compared with saline-injected group
(P<0.05). Genetic deletion of MyD88, TLR2 or TLR9 effectively controlled the
signs of intestinal injury when compared with irinotecan-administered WT controls
(P<0.05). In contrast to the MyD88-/- and TLR2-/- mice, the irinotecan-injected
TLR9-/- mice showed a reduced survival, a marked diarrhea and an enhanced
expression of IL-18 versus irinotecan-injected WT controls. Additionally, the
expression of MyD88 was reduced in the TLR2-/- or TLR9-/- mice. This study shows
a critical role of the MyD88-mediated TLR2 and TLR9 signaling in the pathogenesis
of irinotecan-induced intestinal mucositis.
PMID- 26440614
TI - High Endogenous Expression of Chitinase 3-Like 1 and Excessive Epithelial
Proliferation with Colonic Tumor Formation in MOLF/EiJ Mice.
AB - Colorectal cancer (CRC) development is mediated by uncontrolled survival and
proliferation of tumor progenitor cells. Using animal models to identify and
study host-derived factors that underlie this process can aid interventions in
preventing tumor expansion and metastasis. In healthy steady states in humans and
mice (e.g. C57BL/6 strain), colonic Chitinase 3-like 1 (CHI3L1) gene expression
is undetectable. However, this expression can be induced during intestinal
inflammation and tumorigenesis where CHI3L1 plays an important role in tissue
restitution and cell proliferation. Here, we show that a wild-derived mouse
strain MOLF/EiJ expresses high levels of colonic epithelial CHI3L1 at the steady
state due to several nucleotide polymorphisms in the proximal promoter regions of
the CHI3L1 gene. Interestingly, these mice spontaneously developed polypoid
nodules in the colon with signs of immune cell infiltrations at steady state. The
CHI3L1 positive colonic epithelial cells were highly proliferative and exhibited
malignant transformation and expansion when exposed in vivo to azoxymethane, one
of the well-known colonic carcinogens.
PMID- 26440615
TI - Nonlinear approach to difference imaging in diffuse optical tomography.
AB - Difference imaging aims at recovery of the change in the optical properties of a
body based on measurements before and after the change. Conventionally, the image
reconstruction is based on using difference of the measurements and a linear
approximation of the observation model. One of the main benefits of the
linearized difference reconstruction is that the approach has a good tolerance to
modeling errors, which cancel out partially in the subtraction of the
measurements. However, a drawback of the approach is that the difference images
are usually only qualitative in nature and their spatial resolution can be weak
because they rely on the global linearization of the nonlinear observation model.
To overcome the limitations of the linear approach, we investigate a nonlinear
approach for difference imaging where the images of the optical parameters before
and after the change are reconstructed simultaneously based on the two datasets.
We tested the feasibility of the method with simulations and experimental data
from a phantom and studied how the approach tolerates modeling errors like domain
truncation, optode coupling errors, and domain shape errors.
PMID- 26440616
TI - Multispectral tissue characterization for intestinal anastomosis optimization.
AB - Intestinal anastomosis is a surgical procedure that restores bowel continuity
after surgical resection to treat intestinal malignancy, inflammation, or
obstruction. Despite the routine nature of intestinal anastomosis procedures, the
rate of complications is high. Standard visual inspection cannot distinguish the
tissue subsurface and small changes in spectral characteristics of the tissue, so
existing tissue anastomosis techniques that rely on human vision to guide
suturing could lead to problems such as bleeding and leakage from suturing sites.
We present a proof-of-concept study using a portable multispectral imaging (MSI)
platform for tissue characterization and preoperative surgical planning in
intestinal anastomosis. The platform is composed of a fiber ring light-guided MSI
system coupled with polarizers and image analysis software. The system is tested
on ex vivo porcine intestine tissue, and we demonstrate the feasibility of
identifying optimal regions for suture placement.
PMID- 26440617
TI - Nondestructive observation of teeth post core-space using optical coherence
tomography: comparison with microcomputed tomography and live images.
AB - No previous reports have observed inside the root canal using both optical
coherence tomography (OCT) and x-ray microcomputed tomography (MUCT) for the same
sample. The purpose of this study was to clarify both OCT and MUCT image
properties from observations of the same root canal after resin core build-up
treatment. As OCT allows real-time observation of samples, gap formation may be
able to be shown in real time. A dual-cure, one-step, self-etch adhesive system
bonding agent, and dual-cure resin composite core material were used in root
canals in accordance with instructions from the manufacturer. The resulting OCT
images were superior for identifying gap formation at the interface, while MUCT
images were better to grasp the tooth form. Continuous tomographic images from
real-time OCT observation allowed successful construction of a video of the resin
core build-up procedure. After 10 to 12 s of light curing, a gap with a clear new
signal occurred at the root-core material interface, proceeding from the coronal
side (6 mm from the cemento-enamel junction) to the apical side of the root.
PMID- 26440618
TI - Our empathic brain and suicidal individuals.
PMID- 26440620
TI - Fruits of trauma? Posttraumatic growth among suicide-bereaved parents.
AB - BACKGROUND: While there is evidence that suicide-bereaved individuals may be at
higher risk for trauma-related outcomes, such as posttraumatic stress disorder or
prolonged grief, positive psychology suggests that suicide bereavement may also
promote personal growth within the confines of distress characterized as
posttraumatic growth (PTG). AIMS: The aim of this study was to investigate PTG
and what variables, such as reflective rumination, resilience, personality
variables, and mood states, contribute to PTG among suicide-bereaved parents.
METHOD: Online survey methods were employed using a convenience sample of 154
parents bereaved by the suicide death of their child within 2 years. RESULTS:
Multiple regression analyses revealed that resilience inversely predicted PTG
scores, but reflective rumination did not predict PTG. PTG scores were in the low
moderate range and were lower than those of parents bereaved by other causes of
death. Items endorsed most strongly corresponded to the PTG factors Relating to
Others, Spiritual Change, and Appreciation of Life. CONCLUSION: In this study,
PTG manifests among suicide-bereaved parents, but may be complicated by the
proximity to the death and by concurrent brooding and reflective rumination
unique to answering the question of "why" in this population.
PMID- 26440621
TI - Moderating role of trait hope in the relation between painful and provocative
events and acquired capability for suicide.
AB - BACKGROUND: The interpersonal theory of suicide has gained empirical support as a
conceptualization of suicide risk; however, little research has examined the role
of individual traits, such as trait hope, within the interpersonal theory of
suicide. AIMS: The purpose of this study was to further investigate the role of
trait hope components (i.e., pathways and agency) in acquired capability for
suicide. METHOD: Participants were 711 college students who completed measures of
acquired capability for suicide, painful and provocative events, and trait hope
(i.e., pathways and agency). Linear regression was used to test the hypotheses.
RESULTS: As hypothesized, there was a positive relation between pathways and
acquired capability. Contrary to our hypotheses, after controlling for gender
there was a significant relation between agency and acquired capability. In
addition, after controlling for gender, pathways did not moderate the relation
between painful and provocative events and acquired capability, whereas agency
did moderate this relation. CONCLUSION: Painful and provocative events should be
assessed as a risk factor for acquired capability for suicide, and this may be
more salient for individuals higher in the agency component of trait hope. Future
research should consider examining the role of other traits within the
interpersonal theory of suicide.
PMID- 26440619
TI - Re-examination of classic risk factors for suicidal behavior in the psychiatric
population.
AB - BACKGROUND: For decades we have understood the risk factors for suicide in the
general population but have fallen short in understanding what distinguishes the
risk for suicide among patients with serious psychiatric conditions. AIMS: This
prompted us to investigate risk factors for suicidal behavior among psychiatric
inpatients. METHOD: We reviewed all psychiatric hospital admissions (2008-2011)
to a centralized psychiatric hospital in Ontario, Canada. Using multivariable
logistic regression we evaluated the association between potential risk factors
and lifetime history of suicidal behavior, and constructed a model and clinical
risk score to predict a history of this behavior. RESULTS: The final risk
prediction model for suicidal behavior among psychiatric patients (n = 2,597)
included age (in three categories: 60-69 [OR = 0.74, 95% CI = 0.73-0.76], 70-79
[OR = 0.45, 95% CI = 0.44-0.46], 80+ [OR = 0.31, 95% CI = 0.30-.31]), substance
use disorder (OR = 1.30, 95% CI = 1.27-1.32), mood disorder (OR = 1.49, 95% CI =
1.47-1.52), personality disorder (OR = 2.30, 95% CI = 2.25-2.36), psychiatric
disorders due to general medical condition (OR = 0.52, 95% CI = 0.50-0.55), and
schizophrenia (OR = 0.42, 95% CI = 0.41-0.43). The risk score constructed from
the risk prediction model ranges from -9 (lowest risk, 0% predicted probability
of suicidal behavior) to +5 (highest risk, 97% predicted probability).
CONCLUSION: Risk estimation may help guide intensive screening and treatment
efforts of psychiatric patients with high risk of suicidal behavior.
PMID- 26440622
TI - Ethnic differences in correlates of suicidal behavior among women seeking help
for intimate partner violence.
AB - BACKGROUND: Women abused by an intimate partner are at risk of engaging in
nonfatal suicidal behavior and suicidal communication (NSBSC). No studies have
examined ethnic differences in correlates of NSBSC among abused women. AIMS: This
secondary data analytic study examined whether correlates of NSBSC previously
reported among a mixed ethnic sample of women seeking help for abuse by a male
intimate partner differed for those who self-identified as Latina (N = 340),
African American (N = 184), or European American (N = 67). METHOD: Logistic
regression was used to examine correlates of NSBSC separately among Latina,
African American, and European American women. RESULTS: More severe violence by a
male intimate partner, having a chronic or disabling illness, being younger, and
being unemployed were positively associated with NSBSC in bivariate analyses
among Latina women, but unemployment did not remain significantly associated with
NSBSC in the multiple logistic regression. There were no significant correlates
of NSBSC for African American women. Having a chronic illness was significantly
associated with NSBSC among European American women. CONCLUSION: Findings suggest
the need for culturally tailored suicide prevention interventions and studies
that examine risk and protective factors for NSBSC among a diversity of women
abused by male intimate partners.
PMID- 26440623
TI - Suicide prevention through online gatekeeping using search advertising
techniques: a feasibility study.
AB - BACKGROUND: Nurturing gatekeepers is an effective suicide prevention strategy.
Internet-based methods to screen those at high risk of suicide have been
developed in recent years but have not been used for online gatekeeping. AIMS: A
preliminary study was conducted to examine the feasibility and effects of online
gatekeeping. METHOD: Advertisements to promote e-mail psychological consultation
service use among Internet users were placed on web pages identified by searches
using suicide-related keywords. We replied to all emails received between July
and December 2013 and analyzed their contents. RESULTS: A total of 139
consultation service users were analyzed. The mean age was 23.8 years (SD = 9.7),
and female users accounted for 80% of the sample. Suicidal ideation was present
in 74.1%, and 12.2% had a history of suicide attempts. After consultation,
positive changes in mood were observed in 10.8%, 16.5% showed intentions to seek
help from new supporters, and 10.1% of all 139 users actually took help-seeking
actions. CONCLUSION: Online gatekeeping to prevent suicide by placing
advertisements on web search pages to promote consultation service use among
Internet users with suicidal ideation may be feasible.
PMID- 26440624
TI - Revisiting the concept of knowledge: how much is learned by students
participating in suicide prevention gatekeeper training?
AB - BACKGROUND: Although gatekeeper training is effective at increasing knowledge,
some question the effectiveness of these programs due to high pretraining
knowledge levels. However, knowledge scores may be artificially inflated when
students guess answer options correctly but lack information needed to assist
suicidal peers. AIMS: To use free-recall questions to evaluate suicide prevention
knowledge and compare levels of knowledge using this methodology with established
assessment methods in the literature. METHOD: Free-recall knowledge questions
were examined before and after participation in a student gatekeeper training
program. Focus groups with students enriched interpretation of quantitative
results. RESULTS: Unlike in studies using forced-choice assessment, students'
baseline knowledge was markedly low using free-recall questions and, despite
making significant improvement from pretraining levels, posttraining knowledge
barely approached passable levels. Focus group findings suggest that training
sessions may need to be more engaging and interactive in order to improve
knowledge transfer. CONCLUSION: Free-recall questions may provide a less inflated
measure of accessible knowledge learned from school-based suicide prevention
curricula. Evaluators and programmatic partners should be cognizant of this
methodological issue and consider using a mix of assessment methodologies to
determine students' actual levels of knowledge after participation in gatekeeper
training.
PMID- 26440625
TI - Association between adolescent suicide and sociodemographic factors in Chile:
cross-sectional ecological study.
AB - BACKGROUND: Adolescent suicide rates (ASR) are a matter of concern worldwide.
Causes of this trend are not understood and could correspond to socioeconomic
factors such as inequality. AIM: To investigate sociodemographic variables
related to ASR, particularly the potential association with indicators of
socioeconomic inequality. METHOD: Cross-sectional ecological study analyzing data
from 29 health districts with univariate and multivariable multilevel Poisson
models. RESULTS: ASR were higher in male adolescents and at increasing age. No
association was found between ASR and inequality (Gini coefficient and 20/20
ratio). Analysis revealed that living in a single-parent family is associated
with ASR. CONCLUSIONS: The usual demographic patterns of adolescent suicide apply
in Chile. An emerging variable of interest is single-parent family. No cross
sectional association between social inequality and ASR was found based on
conflicting evidence. These results should be explored in future prospective
population studies to further understand associated social factors.
PMID- 26440626
TI - Trait gratitude and suicidal ideation and behavior: an exploratory study.
AB - BACKGROUND: Despite the progress of positive psychology, current knowledge
regarding suicide protective factors is limited. Trait gratitude (a tendency to
experience gratitude in daily life) may protect against suicidal ideation and
behavior. AIMS: The study tested a model of causal effects among gratitude,
religiosity, reasons for living, coping, and social support as predictors of
suicidal ideation, suicide threats, and suicide attempts after controlling for
depression and stressful life events. METHOD: A sample of 165 college students
were administered measures of gratitude, religiosity, reasons for living, social
support, coping skills, stress, and depression. The study assessed lifetime and
current suicidal ideation as well as lifetime suicide threat and attempt.
RESULTS: Both gratitude and religiosity, along with social support, coping
skills, and reasons for living, correlated negatively with prior suicidal
ideation, but not with prior attempted suicide. After controlling for risk factor
(depression and stress), the impact of gratitude and religiosity was no longer
statistically significant. CONCLUSION: Further research could help understand the
role of positive emotions and human strengths, such as gratitude, in preventing
and alleviating suicidal ideation and behavior.
PMID- 26440628
TI - Induction of Cytotoxicity through Photorelease of Aminoferrocene.
AB - Reactive oxygen species (ROS)-activated aminoferrocene-based anticancer prodrug
candidates successfully take advantage of intrinsically high amounts of ROS in
tumor tissues. Interestingly, the ROS-initiated activation of these prodrug
candidates leads to formation of unstable aminoferrocene (Fc-NH2) derivatives,
which decay to iron ions. The latter catalytically increases ROS concentration to
a lethal level. In this work, we prepared light-controlled aminoferrocene prodrug
candidates by derivatizing Fc-NH2 with an o-nitrophenyl and an o-nitrobiphenyl
photolabile protecting group (PLPG), respectively, and by further conjugation to
a mitochondria localization signal (MLS) peptide (Cys-D-Arg-Phe-Lys-NH2). The
resulting bioconjugates were found to be more stable and less cytotoxic, in the
dark, toward human promyelocytic leukemia cells (HL-60) compared to Fc-NH2. Upon
light irradiation at 355 nm, both conjugates released Fc-NH2, albeit with very
different photolysis quantum yields. The o-nitrobiphenyl photocage was in fact
several orders of magnitude more efficient than the o-nitrophenyl photocage in
releasing Fc-NH2. This difference was reflected by the light irradiation
experiments on the HL-60 cell line, in which aminoferrocene conjugated with the o
nitrobiphenyl cage and the MLS displayed the highest phototoxicity index (2.5 +/-
0.4) of all the compounds tested. The iron release assays confirmed the rise in
iron ion concentrations upon light irradiation of both caged aminoferrocene
derivatives. Together with the absence of phototoxicity on the nonmalignant hTERT
immortalized retinal pigment epithelial (hTERT RPE-1) cell line, these results
indicate catalytic generation of ROS as possible mode of action.
PMID- 26440629
TI - Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti
TNF Response in Patients with Rheumatoid Arthritis.
AB - OBJECTIVES: To determine whether genetic variation within genes related to the
Toll-like receptor, inflammasome and interferon-gamma pathways contributes to the
differences in treatment response to tumour necrosis factor inhibitors (anti-TNF)
in patients with rheumatoid arthritis (RA). METHODS: In a retrospective case-case
study, we assessed 23 functional single nucleotide polymorphisms (SNPs) in 15
genes. We included 538 anti-TNF naive Danish RA patients from the nationwide
DANBIO database. Multivariable logistic regression analyses were performed to
detect associations (p-value<0.05) between genotypes and European League Against
Rheumatism (EULAR) treatment responses. False Discovery Rate corrections for
multiple testing (q-value) and stratified analyses were performed to investigate
association with individual therapies and IgM-rheumatoid factor (RF) status.
RESULTS: Six of twenty successfully genotyped polymorphisms were nominally
associated with EULAR treatment response. Three of these were in weak to moderate
linkage disequilibrium with polymorphisms previously reported associated with
anti-TNF treatment response. TLR5(rs5744174) variant allele carriers (odds
ratio(OR) = 1.7(1.1-2.5),p = 0.010,q = 0.46) and TLR1(rs4833095) homozygous
variant carriers (OR = 2.8(1.1-7.4),p = 0.037,q = 0.46) had higher odds for a
positive treatment response. NLRP3(rs10754558) variant allele carriers (odds
ratio(OR) = 0.6(0.4-1.0),p = 0.045,q = 0.46) were more likely to have a negative
treatment response. The association in TLR5(rs5744174) remained significant after
correction for multiple comparisons among patients negative for RF (OR = 6.2(2.4
16.3),p = 0.0002,q = 0.024). No other association withstood correction for
multiple testing. Post hoc analyses showed that change in Patient Global score on
a visual analogue scale (VAS) and change in pain VAS were the main factors
responsible for the association. CONCLUSIONS: We reproduced previously reported
associations between genetic variation in the TLR10/1/6 gene cluster, TLR5, and
NLRP3 loci and response to anti-TNF treatment in RA. Changes in VAS pain and
patient global scores were the main contributors to the association found for
TLR5. Furthermore, we identified other candidate genes that require replication
in independent cohorts.
PMID- 26440630
TI - [Mechanical thrombectomy for acute ischemic stroke : current evidence and open
questions].
AB - OBJECTIVE: To determine the importance of mechanical thrombectomy (MT) in the
treatment of ischemic stroke. MATERIAL AND METHODS: Analysis and comparison of
randomized controlled trials (RCT) of MT versus i.v. thrombolysis (IVT)
considering pathophysiological and logistic aspects. RESULTS: The use of MT is
more effective than IVT for internal carotid artery terminus (ICAT), M1 segment
and tandem occlusions, i.e. proximal internal carotid artery (ICA) occlusion or
stenosis, even in patients older than 75-80 years of age. Due to the small sample
sizes this question cannot be answered for patients with M2 occlusions. It is
still uncertain whether MT is needed in patients with a low National Institutes
of Health stroke scale (NIHSS) score, whether IVT is needed before MT and what
type of imaging should be performed. Approximately one third of eligible patients
currently undergo MT in Germany. Results from RCTs with stent retrievers for
patients with vertebrobasilar artery occlusions are lacking. CONCLUSION: After
becoming established as a first-line therapy for patients with ICAT, M1 segment
and tandem occlusions, the effectiveness of MT with stent retrievers has to
proven in patients with more distal occlusions, low NIHSS scores and even
vertebrobasilar artery occlusions.
PMID- 26440631
TI - [Diagnosis and treatment options in vertigo syndromes].
AB - The key to diagnosing vertigo and balance disorders is systematic analysis of
case history with clinical examination of the vestibular, oculomotor, and
cerebral systems in particular. Important criteria for differentiating between
the various vertigo syndromes are 1) the time course of symptoms, 2) the type of
symptoms, 3) modulating factors, and 4) associated symptoms. For clinical
examination of the vestibular system, six important tests are available:
assessment of spontaneous nystagmus, head impulse test, dynamic visual acuity,
subjective visual verticality, positioning manoeuvre, and the Romberg test/gait
analysis with eyes open and closed. On the basis of five clinical signs (vertical
divergence, central fixation nystagmus, gaze-evoked nystagmus, saccades, normal
head impulse test), the clinical examination is able to differentiate between
acute central and peripheral vestibular syndromes with a sensitivity and
specificity of over 90%. The most relevant laboratory examinations are caloric
irrigation and the video head-impulse test for canal function and the vestibular
evoked myogenic potentials for otolith function. Finally, treatment is based upon
four therapeutic principles: physiotherapy, pharmacotherapy, psychotherapy, and
in rare cases, surgery.
PMID- 26440633
TI - [Not Available].
PMID- 26440634
TI - Carboxylic Derivatives of Vitamin K2 Inhibit Hepatocellular Carcinoma Cell Growth
through Caspase/Transglutaminase-Related Signaling Pathways.
AB - Chemoprevention of hepatocellular carcinoma (HCC) is one of the most challenging
aspects of medical research. Vitamin K2 (VK2) has been suggested for its
chemopreventive role in treatment of HCC, while inconsistent results in clinical
trials have been reported. The present study was initiated to add to our insight
into the anti-HCC cell proliferative effect of VK2 and its derivatives from a
viewpoint of chemical structure. No significant effect was observed with original
VK2, while VK2 derivatives bearing both isoprene units and a carboxyl-terminated
side chain dose-dependently inhibited the growth of HCC cells without affecting
normal liver cells. Loss-of-function analyses revealed that the anti-HCC cell
activity by the VK2 derivatives was not mediated by a VK2 binding protein Bcl-2
homologous antagonist/killer (Bak) but rather associated with
caspase/transglutaminase-related signaling pathways. Further studies on the
carboxylic derivatives of VK2 bearing isoprene structural units introduced in
this study might shed new light on the systemic treatment and prevention of HCC.
PMID- 26440635
TI - Serum Fatty Acid Binding Protein 4 Concentrations Are Positively and
Independently Associated with Blood Pressure and Abdominal Fat among Parameters
in Health Check-Ups in Ordinary Middle-Aged Japanese Males.
AB - We wished to examine potential associations among blood concentrations of fatty
acid-binding protein (FABP) 4 and parameters in health check-ups such as
abdominal fat area (AFA) and blood pressure (BP) in middle-aged Japanese males.
We conducted a cross-sectional study of males who participated in health check
ups in Japan. We excluded participants diagnosed with metabolic diseases by the
time of their check-up. A total of 305 subjects (30-64 [mean+/-standard
deviation, 47.3+/-8.5] y) were recruited. Areas of total-abdominal, visceral and
subcutaneous fat were measured using computed tomography. We compared the
association of serum concentrations of FABP4 with various clinical parameters by
Pearson product-moment correlation coefficient (PPMCC) analyses, and by step-wise
multivariate linear regression analyses (MLRA). PPMCC analyses showed that blood
concentrations of FABP4 were positively associated with: body mass index; areas
of fat (total abdominal, visceral, subcutaneous); systolic BP; diastolic BP;
total cholesterol; low-density lipoprotein-cholesterol; triacylglycerol;
activities of gamma-glutamyl transpeptidase, aspartate aminotransferase and
alanine aminotransferase; white blood cell count; and levels of creatinine. Step
wise MLRA showed that AFAs (visceral and subcutaneous) and diastolic BP were
positively and independently associated with serum concentrations of FABP4 among
the parameters tested. These data suggest that serum concentrations of FABP4 are
independently and positively associated with BP and AFA among parameters measured
in health check-ups in middle-aged Japanese males.
PMID- 26440636
TI - Effects of Aerobic Exercise on Postprandial Carbohydrate and Lipoprotein
Metabolism Following Cookie Ingestion in Healthy Young Women.
AB - We examined the acute effects of postprandial aerobic exercise on glucose and
lipid metabolism following cookie ingestion. Fifteen healthy young women with a
sedentary lifestyle, normal weight and apolipoprotein E3/3 participated. After a
12-h overnight fast, each subject ingested a cookie (1.53 g/kg, Meal Test C) and
then performed two trials, one with postprandial exercise (E trial) and one
without exercise (C trial), in a randomized crossover design. A single 30-min
bout of walking exercise was performed 20 min after the cookie intake. Venous
blood samples were drawn before (0 h) and 20 min and 1, 2, 4, and 6 h after
cookie ingestion. The Deltaglucose concentration was not significantly different
between the two trials, but the Deltainsulin concentration at 1 h and the
incremental area under the curve (IAUC) (0-2 h)-insulin in the E trial were
significantly lower than in the C trial. The ratio of glucose/insulin at 1 h was
significantly higher in the E trial than in the C trial. The DeltaTG, DeltaRLP
TG, DeltaapoB48 and DeltaRemL-C concentrations at 1 h in the E trial were
significantly higher than in the C trial. The IAUC (0-2 h)-apoB48 in the E trial
was significantly larger than in the C trial. Postprandial exercise showed an
insulin-sparing effect following the cookie ingestion by increasing insulin
sensitivity. However, postprandial exercise transiently stimulated the secretion
of exogenous apoB48-containing lipoprotein during the early period, and no
further effects were observed. These results suggest that postprandial aerobic
exercise is effective for the promotion of postprandial carbohydrate metabolism,
but not lipidemia.
PMID- 26440637
TI - Boysenberry Polyphenols Suppressed Elevation of Plasma Triglyceride Levels in
Rats.
AB - Boysenberry, a hybrid Rubus berry, is mainly cultivated in New Zealand. We
previously reported that consumption of boysenberry juice (BBJ) exhibited anti
obesity effects in high-fat feeding rats. In this study, we focused on the
suppressive effect of BBJ and its fraction on triglyceride absorption from the
gastrointestinal tract. BBJ effectively inhibited pancreatic lipase activity in
vitro, and was separated into four fractions (Fr1, Fr2, Fr3 and Fr4) by HP-20
column chromatography. Among all the fractions, Fr3, the ellagic acid-rich
fraction, showed the most potent inhibition against pancreatic lipase in vitro
with Fr2, the anthocyanin-rich fraction, second. Authentic ellagic acid
equivalent in Fr3 showed poor activity against pancreatic lipase. Then, each
fraction was orally administered with corn oil to rats fitted with a jugular
catheter to examine the effects of each fraction on plasma triglyceride levels.
Both Fr2 and Fr3 effectively suppressed the plasma triglyceride level elevation
at a dose of 1,000 mg/kg body weight. These findings demonstrated that BBJ
contains chemical components which inhibit triglyceride absorption from the
gastrointestinal tract.
PMID- 26440638
TI - Treatment with DPP-4I Anagliptin or alpha-GI Miglitol Reduces IGT Development and
the Expression of CVD Risk Factors in OLETF Rats.
AB - It has been reported that postprandial hyperglycemia from the pre-diabetic stage,
especially from the impaired glucose tolerance (IGT) stage, is positively
associated with subsequent incidences of cardiovascular diseases (CVD) and type 2
diabetes. In this study, we aimed to investigate whether treatment with a
dipeptidyl peptidase-4 inhibitor (DPP-4I) or an alpha-glucosidase inhibitor
(alpha-GI), either of which suppresses postprandial hyperglycemia, reduces the
expression of CVD risk factors in an IGT animal model. A DPP-4I, anagliptin
(1,200 ppm), or an alpha-GI, miglitol (600 ppm), in the diet was administered for
47 wk to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for
spontaneously-developed type 2 diabetes, at the IGT stage. We examined whether
each treatment reduced the expression of CVD risk factors such as inflammatory
cytokines/cytokine-like factors in peripheral leukocytes and adhesion molecules
in the aortic tissues and circulation. Treatment with either drug reduced IGT
development and repressed expression of the interleukin-1beta, tumor necrosis
factor-alpha, S100a9, and S100a11 genes in peripheral leukocytes in the fasting
state at weeks 25 and 39. The mRNA levels of E-selectin in aortic tissues and
protein levels of the soluble forms of E-selectin and ICAM-1 in arterial blood
were significantly lower in the anagliptin and miglitol groups than in the
control group. Our results suggest that long-term treatment with anagliptin or
miglitol in OLETF rats at the IGT stage suppresses the expression of inflammatory
cytokines in peripheral leukocytes and adhesion molecules in aortic tissues.
PMID- 26440640
TI - Efficacy and Safety of High Specific Volume Polysaccharide-A New Type of Dietary
Fiber for Treatment of Functional Constipation and IBS-C.
AB - We investigated the efficacy and safety of a new type of dietary fiber (high
specific volume polysaccharide) for use in treating constipation of different
etiologies. Functional constipation patients and irritable bowel syndrome
constipation (IBS-C) patients were administrated high specific volume
polysaccharide (HSVP) three times daily for a period of 2 wk to relieve their
symptoms. Scores on a stool form scale, and patient reports of straining during a
bowel movement, having sensations of an incomplete bowel movement or a blocked
anorectum, and abnormal defecation intervals were recorded, graded, and scored by
a functional constipation sample group. Similarly, a cohort of IBS-C patients
reported their occurrence of abdominal discomfort or pain, abnormal stool
formation, defecation frequency, and straining during a bowel movement.
Additionally, both groups reported any adverse reactions associated with taking
HSVP. All patients in both groups returned for follow-up visits, and no adverse
reactions to treatment with HSVP were reported. In the functional constipation
group, HSVP was effective for treating symptoms of constipation in 81.46% and
93.17% of patients after 7 and 14 d of dosing, respectively (both p<0.05). In the
IBS-C group, symptoms of constipation were relieved in 71.67% and 88.34% of
patients after 7 and 14 d of dosing, respectively (both p<0.05). High specific
volume polysaccharide was shown be effective for treatment of functional
constipation and IBS-C, without causing significant adverse events.
PMID- 26440639
TI - Selenium Intake in Hypertensive and Normotensive Post-Menopausal Indonesian
Women.
AB - The Indonesian Ministry of Health has predicted that the national prevalence of
hypertension in Indonesia may reach 26.5% in 2013. Increasing age, stress, lack
of physical activity, obesity and passive smoking are known to be risk factors of
hypertension. In women over 50 y, hormonal changes that occur post-menopause may
also increase the risk of hypertension and other vascular diseases. Antioxidant
precursors, such as selenium, however, are known to provide protection against
the development of several oxidative stress-related diseases, including
hypertension. To prove the hypothesis, we compared the levels of consumption of
selenium in hypertensive and normotensive post-menopausal women. An observational
comparative study with cross-sectional design was conducted in groups of post
menopausal women with hypertension and those who are normotensive. Structured
interviews and food recall of 2*24 h were used to determine the level of
consumption, and the Depression, Anxiety and Stress Scale (DASS) questionnaire
was used to measure the level of stress. The result suggests a significant
difference in the levels of selenium intake between the normotensive and
hypertensive groups (p=0.008). Furthermore, the passive smoking and stress levels
of the hypertensive group were significantly higher than those of the
normotensive group. These result support the hypothesis that selenium may play a
protective role in vascular disease.
PMID- 26440641
TI - Effect of Kiwifruit on Bone Resorption in Ovariectomized Mice.
AB - Kiwifruit is a good source of dietary components and has beneficial effects for
health. In this study, we investigated the effects of two types of kiwifruit,
green kiwifruit (GRK) and gold kiwifruit (GOK), on bone metabolism in
ovariectomized (OVX) mice. Seven-week-old female Balb/c-strain mice were divided
into four groups: sham-operated (sham) group, OVX group, and OVX mice that were
fed a GRK-supplemented diet or GOK-supplemented diet. Freeze-dried GRK and GOK
were prepared and added in the diet at a concentration of 3 g/100 g. After 9 wk,
the mice were sacrificed, and the serum, uterus, and femurs were obtained. Final
body weight did not differ significantly among the four groups. Compared to the
sham group, uterine weight was significantly lower and serum C-terminal
telopeptide of type I collagen (CTx) levels and receptor activator of NF-kappaB
ligand (RANKL) mRNA expression of the whole femur were significantly higher in
the OVX group. Compared to the OVX group, GRK, but not GOK, reduced serum CTx
concentrations and RANKL mRNA expression of the whole femur without changes in
uterine weight. These results suggest that the GRK inhibited bone resorption,
which might be due to a decrease in RANKL mRNA expression in OVX mice.
PMID- 26440642
TI - Polyphenol Intake from Beverages in Japan over an 18-Year Period (1996-2013):
Trends by Year, Age, Gender and Season.
AB - An association between the dietary intake of polyphenols and human health has
been shown in many epidemiological studies. Since beverages are rich sources of
polyphenols, we aimed to evaluate the polyphenol intake from beverages in
Japanese individuals with a focus on differences according to year, age, gender
and season. More than 10,000 Japanese male and female subjects aged 1-99 y old
participated in this survey every year from 1996 to 2013, and their beverage
consumption and amount of polyphenol intake were calculated. Polyphenol intake
from beverages in Japan showed no tendency to increase or decrease over the 18-y
period, and the major sources of polyphenols in Japanese daily life were coffee
and green tea. Polyphenol intake was larger in participants with higher age up to
59 y old in both male and female subjects. There was a slight difference in
polyphenol intake by gender, with adult males consuming more polyphenols than
adult females. Polyphenols were consumed slightly more in the winter than the
summer, although the seasonal difference in polyphenol intake was not large. Our
results suggest that polyphenol intake from beverages is influenced by age rather
than gender or season in Japan, and may not have changed over time, at least over
the 18-y period beginning in 1996 in Japan.
PMID- 26440643
TI - Effect of Polydextrose Intake on Constipation in Japanese Dialysis Patients: A
Triple-Blind, Randomized, Controlled Trial.
AB - The objective of the present study was to evaluate bowel habits induced by
ingestion of 10 g polydextrose (PDX) fed to Japanese hemodialysis (HD) patients.
This was a randomized, placebo-controlled, triple-blind, parallel-group
controlled, 8-wk study. A total of 50 HD outpatients capable of self-management
(51-79 y of age) were recruited at H Clinic, Japan. Inclusion criteria for
participation in the study were ingestion of one or more laxative tablets for
more than 3 mo and having received HD for more than 6 mo. The participants were
randomly assigned to 2 groups: A (0 g polydextrose/d; control), B (10 g
polydextrose/d; PDX). The primary outcome measure was stool frequency. Secondary
outcomes were stool consistency, abdominal pain, intestinal bloating and clinical
biochemistry indexes. PDX had no significant effect on blood biochemistry
indexes. The PDX group showed significant improvements in bowel function (stool
frequency increased from 3.0 times per week to 7.5 times per week) and reported
no laxation problems (abdominal distention, cramps, and diarrhea) (p<0.01).
Regular consumption of the PDX products increased dietary fiber intake to
recommended levels and improved bowel habits.
PMID- 26440644
TI - Feasibility of long-distance heart rate monitoring using transmittance
photoplethysmographic imaging (PPGI).
AB - Photoplethysmography (PPG) devices are widely used for monitoring cardiovascular
function. However, these devices require skin contact, which restricts their use
to at-rest short-term monitoring. Photoplethysmographic imaging (PPGI) has been
recently proposed as a non-contact monitoring alternative by measuring blood
pulse signals across a spatial region of interest. Existing systems operate in
reflectance mode, many of which are limited to short-distance monitoring and are
prone to temporal changes in ambient illumination. This paper is the first study
to investigate the feasibility of long-distance non-contact cardiovascular
monitoring at the supermeter level using transmittance PPGI. For this purpose, a
novel PPGI system was designed at the hardware and software level. Temporally
coded illumination (TCI) is proposed for ambient correction, and a signal
processing pipeline is proposed for PPGI signal extraction. Experimental results
show that the processing steps yielded a substantially more pulsatile PPGI signal
than the raw acquired signal, resulting in statistically significant increases in
correlation to ground-truth PPG in both short- and long-distance monitoring. The
results support the hypothesis that long-distance heart rate monitoring is
feasible using transmittance PPGI, allowing for new possibilities of monitoring
cardiovascular function in a non-contact manner.
PMID- 26440646
TI - High performance of PbSe/PbS core/shell quantum dot heterojunction solar cells:
short circuit current enhancement without the loss of open circuit voltage by
shell thickness control.
AB - We fabricated heterojunction solar cells with PbSe/PbS core shell quantum dots
and studied the precisely controlled PbS shell thickness dependency in terms of
optical properties, electronic structure, and solar cell performances. When the
PbS shell thickness increases, the short circuit current density (JSC) increases
from 6.4 to 11.8 mA cm(-2) and the fill factor (FF) enhances from 30 to 49% while
the open circuit voltage (VOC) remains unchanged at 0.46 V even with the
decreased effective band gap. We found that the Fermi level and the valence band
maximum level remain unchanged in both the PbSe core and PbSe/PbS core/shell with
a less than 1 nm thick PbS shell as probed via ultraviolet photoelectron
spectroscopy (UPS). The PbS shell reduces their surface trap density as confirmed
by relative quantum yield measurements. Consequently, PbS shell formation on the
PbSe core mitigates the trade-off relationship between the open circuit voltage
and the short circuit current density. Finally, under the optimized conditions,
the PbSe core with a 0.9 nm thick shell yielded a power conversion efficiency of
6.5% under AM 1.5.
PMID- 26440647
TI - A Systematic Review of Patients' Experiences in Communicating with Primary Care
Physicians: Intercultural Encounters and a Balance between Vulnerability and
Integrity.
AB - Communication difficulties persist between patients and physicians. In order to
improve care, patients' experiences of this communication must be understood. The
main objective of this study is to synthesize qualitative studies exploring
patients' experiences in communicating with a primary care physician. A secondary
objective is to explore specific factors pertaining to ethnic minority or
majority patients and their influence on patients' experiences of communication.
Pertinent health and social sciences electronic databases were searched
systematically (PubMed, Cinahl, PsychNet, and IBSS). Fifty-seven articles were
included in the review on the basis of being qualitative studies targeting
patients' experiences of communication with a primary care physician. The meta
ethnography method for qualitative studies was used to interpret data and the
COREQ checklist was used to evaluate the quality of included studies. Three
concepts emerged from analyses: negative experiences, positive experiences, and
outcomes of communication. Negative experiences related to being treated with
disrespect, experiencing pressure due to time constraints, and feeling helpless
due to the dominance of biomedical culture in the medical encounter. Positive
experiences are attributed to certain relational skills, technical skills, as
well as certain approaches to care privileged by the physician. Outcomes of
communication depend on patients' evaluation of the consultation. Four categories
of specific factors exerted mainly a negative influence on consultations for
ethnic minorities: language barriers, discrimination, differing values, and
acculturation. Ethnic majorities also raised specific factors influencing their
experience: differing values and discrimination. Findings of this review are
limited by the fact that more than half of the studies did not explore cultural
aspects relating to this experience. Future research should address these aspects
in more detail. In conclusion, all patients seemed to face additional cultural
challenges. Findings provide a foundation for the development of tailored
interventions to patients' preferences, thus ensuring more satisfactory
experiences. Health care providers should be sensitive to specific factors
(cultural and micro-cultural) during all medical encounters.
PMID- 26440648
TI - Expression of a kinase-dead form of CPK33 involved in florigen complex formation
causes delayed flowering.
AB - Regulation of flowering time is crucial for reproductive success of plants.
FLOWERING LOCUS T (FT) protein is a central component of florigen and forms a
ternary complex with 14-3-3 and FD, a basic leucine zipper transcription factor,
in the shoot apex and promotes flowering. This complex formation requires
phosphorylation of threonine residue at position 282 of FD. A calcium-dependent
protein kinase CPK33 is responsible for the phosphorylation. However, possibly
due to functional redundancy among calcium-dependent protein kinases, impact of
the loss of CPK33 reported in the previous study was rather limited. Here, we
report that expression of a kinase-dead form of CPK33 caused a clear delayed
flowering phenotype, supporting for an important role of CPK33 in florigen
function through FD phosphorylation.
PMID- 26440650
TI - Short QT Syndrome in Current Clinical Practice.
AB - Short QT syndrome is a rare inherited autosomal dominant cardiac channelopathy
associated with malignant ventricular and atrial arrhythmias. A shortened
corrected QT interval is a marker for risk of malignant arrhythmias, which are
secondary to increased transmural dispersion of repolarization. The underlying
gain of function mutations in the potassium channels are most common but genetic
testing remains low yield. This review discusses the cellular mechanisms, genetic
involvement, clinical presentation, and current recommended management of
patients with short QT syndrome relevant to current clinical practice.
PMID- 26440649
TI - Association between the angiotensin-converting enzyme gene insertion/deletion
polymorphism and susceptibility to systemic lupus erythematosus in an Indian
population.
PMID- 26440651
TI - Use of Extracorporeal Membrane Oxygenation in Refractory Cardiogenic Shock.
AB - Cardiogenic shock is a condition marked by low cardiac output and end-organ
hypoperfusion frequently requiring hemodynamic support, and it carries a high
mortality. Extracorporeal membrane oxygenation (ECMO) is an effective tool in
providing mechanical circulatory support in patients with cardiogenic shock
refractory to conventional medical therapies. ECMO can be an essential bridge to
recovery, ventricular assist device implantation or transplant. A
multidisciplinary team approach is needed in managing such patients and intensive
monitoring is required to avoid complications from ECMO. Nevertheless, randomized
clinic trials are warranted to prove a survival benefit.
PMID- 26440652
TI - The Relationship Between Trust-in-God, Positive and Negative Affect, and Hope.
AB - We aimed to test the relationships between Trust-in-God, positive and negative
affect, and feelings of hope. A sample of university students (N = 282, 50 %
female) completed the Positive and Negative Affect Schedule, the Adult
Dispositional Hope Scale, and a Persian measure of Trust-in-God for Muslims. The
results of a series of hierarchical regression analyses indicated that Trust-in
God was positively associated with participants' scores for hope and positive
affect but was negatively associated with their scores for negative affect. The
results support the relationship between Trust-in-God and indices of mental
health.
PMID- 26440653
TI - Muscle Strength, Function and Heart Autonomic Regulation System Recovery at the
Sub-Acute Stage Post Stroke.
AB - BACKGROUND: To compare the rate of recovery of motor and functional ability and
heart rate variability (HRV) parameters during the inpatient rehabilitation
period. SUMMARY: Twenty-three patients post first stroke at the sub-acute phase
underwent motor and functional ability and HRV assessments 20 and 50 days after
the event. A significant improvement was noted in motor and functional ability
performance during the follow-up period, while no such change was noted in the
HRV parameters. KEY MESSAGES: Patients post first-ever stroke exhibited a
significant motor and functional improvement during the sub-acute phase post
stroke, while no change was noted in their HRV parameters, which may imply that
no significant changes in the sympatho-vagal balance took place during this
period.
PMID- 26440654
TI - Myelination Is Associated with Processing Speed in Early Childhood: Preliminary
Insights.
AB - Processing speed is an important contributor to working memory performance and
fluid intelligence in young children. Myelinated white matter plays a central
role in brain messaging, and likely mediates processing speed, but little is
known about the relationship between myelination and processing speed in young
children. In the present study, processing speed was measured through inspection
times, and myelin volume fraction (VFM) was quantified using a multicomponent
magnetic resonance imaging (MRI) approach in 2- to 5-years of age. Both
inspection times and VFM were found to increase with age. Greater VFM in the
right and left occipital lobes, the body of the corpus callosum, and the right
cerebellum was significantly associated with shorter inspection times, after
controlling for age. A hierarchical regression showed that VFM in the left
occipital lobe predicted inspection times over and beyond the effects of age and
the VFM in the other brain regions. These findings are consistent with the
hypothesis that myelin supports processing speed in early childhood.
PMID- 26440655
TI - Characteristics of Hospitalized Cases of Pertussis in Catalonia and Navarra, Two
Regions in the North of Spain.
AB - Pertussis causes a large number of cases and hospitalizations in Catalonia and
Navarra. We made a study of household cases of pertussis during 2012 and 2013 in
order to identify risk factors for hospitalization in pertussis cases. Each
primary case reported triggered the study of their contacts. Close contacts at
home and people who were in contact for >2 hours during the transmission period
of cases were included. The adjusted OR and 95% confidence intervals (CI) was
calculated using logistic regression. A total of 1124 pertussis cases were
detected, of which 14.9% were hospitalized. Inspiratory whoop (aOR: 1.64; CI:
1.02-2.65), apnoea (aOR: 2.47; CI: 1.51-4.03) and cyanosis (aOR: 15.51; CI: 1.87
128.09) were more common in hospitalized than in outpatient cases.
Hospitalization occurred in 8.7% of correctly-vaccinated cases, 41.1% of non
vaccinated cases and 9.4% of partially-vaccinated cases. In conclusion,
inspiratory whoop, apnoea and cyanosis were associated factors to hospitalization
while vaccination reduced hospitalizations due to pertussis.
PMID- 26440656
TI - Sustainable Remediation of Legacy Mine Drainage: A Case Study of the Flight 93
National Memorial.
AB - Pollution from mining activities is a global environmental concern, not limited
to areas of current resource extraction, but including a broader geographic area
of historic (legacy) and abandoned mines. The pollution of surface waters from
acid mine drainage is a persistent problem and requires a holistic and
sustainable approach to addressing the spatial and temporal complexity of mining
specific problems. In this paper, we focus on the environmental, socio-economic,
and legal challenges associated with the concurrent activities to remediate a
coal mine site and to develop a national memorial following a catastrophic event.
We provide a conceptual construct of a socio-ecological system defined at several
spatial, temporal, and organizational scales and a critical synthesis of the
technical and social learning processes necessary to achieving sustainable
environmental remediation. Our case study is an example of a multi-disciplinary
management approach, whereby collaborative interaction of stakeholders, the
emergence of functional linkages for information exchange, and mediation led to
scientifically informed decision making, creative management solutions, and
ultimately environmental policy change.
PMID- 26440658
TI - [The silent revolution].
PMID- 26440657
TI - Intranasal Immunization with DOTAP Cationic Liposomes Combined with DC
Cholesterol Induces Potent Antigen-Specific Mucosal and Systemic Immune Responses
in Mice.
AB - Despite the progress made by modern medicine, infectious diseases remain one of
the most important threats to human health. Vaccination against pathogens is one
of the primary methods used to prevent and treat infectious diseases that cause
illness and death. Vaccines administered by the mucosal route are potentially a
promising strategy to combat infectious diseases since mucosal surfaces are a
major route of entry for most pathogens. However, this route of vaccination is
not widely used in the clinic due to the lack of a safe and effective mucosal
adjuvant. Therefore, the development of safe and effective mucosal adjuvants is
key to preventing infectious diseases by enabling the use of mucosal vaccines in
the clinic. In this study, we show that intranasal administration of a cationic
liposome composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 3beta
[N-(N',N'-dimethylaminoethane)-carbamoyl] (DC-chol) (DOTAP/DC-chol liposome) has
a potent mucosal adjuvant effect in mice. Intranasal vaccination with ovalbumin
(OVA) in combination with DOTAP/DC-chol liposomes induced the production of OVA
specific IgA in nasal tissues and increased serum IgG1 levels, suggesting that
the cationic DOTAP/DC-chol liposome leads to the induction of a Th2 immune
response. Additionally, nasal-associated lymphoid tissue and splenocytes from
mice treated with OVA plus DOTAP/DC-chol liposome showed high levels of IL-4
expression. DOTAP/DC-chol liposomes also enhanced OVA uptake by CD11c+ dendritic
cells in nasal-associated lymphoid tissue. These data demonstrate that DOTAP/DC
chol liposomes elicit immune responses via an antigen-specific Th2 reaction.
These results suggest that cationic liposomes merit further development as a
mucosal adjuvant for vaccination against infectious diseases.
PMID- 26440659
TI - The significance of aortic valve calcification in patients with bicuspid aortic
valve disease.
AB - Bicuspid aortic valve (BAV) is a common congenital heart disease. Our study was
to analyze clinical features of BAV and evaluate whether aortic valve calcium
score (AVCS) was a reliable marker for aortic stenosis (AS) in patients with BAV.
101 patients with BAV who both underwent echocardiology and cardiac computed
tomography (CT) scan in our institution were included. Basic clinical data,
haemodynamic feature, aortic valve and coronary calcium score were collected and
compared among patients with different valve function and different degree of AS.
Risk factors related to severe AS were evaluated by logistic regression, and a
receiver operative characteristic curve was used to determine the cutoff calcium
score greater than which the diagnosis of severe AS was optimized. Patients with
aortic regurgitation (AR) were younger and demonstrated larger aortic annulus and
sinus compared with patients with other valve dysfunction. Aortic valve calcium
score was higher in patients with AS than with AR. For patients with different
degree of AS, there were statistical significances in the value of age, aortic
valve calcium score and coronary calcium score. AVCS was positively related to
severe AS with an odd ratio of 1.286 (95% CI 1.099-1.504) by every 300 points
increase. AVCS was also a strong predictor for severe AS with area under the
curve 0.855 with a cutoff value of 897 (sensitivity 86.7%, specificity 72.2%).
Conclusively, aortic calcium score calculated by quantitative CT is a reliable
marker in evaluating severity of AS.
PMID- 26440660
TI - Validity of the size-specific dose estimate in adults undergoing coronary CT
angiography: comparison with the volume CT dose index.
AB - Size-specific dose estimate (SSDE) takes into account the patient size but
remains to be fully validated for adult coronary computed tomography angiography
(CCTA). We investigated the appropriateness of SSDE for accurate estimation of
patient dose by comparing the SSDE and the volume CT dose index (CTDIvol) in
adult CCTA. This prospective study received institutional review board approval,
and informed consent was obtained from each patient. We enrolled 37 adults who
underwent CCTA with a 320-row CT. High-sensitivity metal oxide semiconductor
field effect transistor dosimeters were placed on the anterior chest. CTDIvol
reported by the scanner based on a 32-cm phantom was recorded. We measured chest
diameter to convert CTDIvol to SSDE. Using linear regression, we then correlated
SSDE with the mean measured skin dose. We also performed linear regression
analyses between the skin dose/CTDIvol and the body mass index (BMI), and the
skin dose/SSDE and BMI. There was a strong linear correlation (r = 0.93, P <
0.001) between SSDE (mean 37 +/- 22 mGy) and mean skin dose (mean 17.7 +/- 10
mGy). There was a moderate negative correlation between the skin dose/CTDIvol and
BMI (r = 0.45, P < 0.01). The skin dose/SSDE was not affected by BMI (r = 0.06, P
> 0.76). SSDE yields a more accurate estimation of the radiation dose without
estimation errors attributable to the body size of adult patients undergoing
CCTA.
PMID- 26440661
TI - A new caring by the ground for severe stage of dementia.
AB - Patients with severe stage of dementia present several psycho-behavioral
disorders, caused by an altered perception of their environment and a feeling of
isolation. Most of them are bedridden because of the advanced stage of
Alzheimer's disease which causes cognitive dysfunctions and physical disorders,
including coordination movement problems. Consequently, their freedoms of
movement are limited as well as the quality of their communication. In this
study, a new care support using activities on the ground is proposed to
compensate for the massive cognitive and psychological losses and enhance their
communication skills. The results of this study show that ground activities seem
to be a promising way to reduce psycho-behavioral disorders and recreate
communication link of the patients presenting with a severe stage of dementia.
PMID- 26440662
TI - Functional decline and herpes zoster in older people: an interplay of multiple
factors.
AB - Herpes zoster is a frequent painful infectious disease whose incidence and
severity increase with age. In older people, there is a strong bidirectional link
between herpes zoster and functional decline, which refers to a decrement in
ability to perform activities of daily living due to ageing and disabilities.
However, the exact nature of such link remains poorly established. Based on the
opinion from a multidisciplinary group of experts, we here propose a new model to
account for the interplay between infection, somatic/psychiatric comorbidity,
coping skills, polypharmacy, and age, which may account for the functional
decline related to herpes zoster in older patients. This model integrates the
risk of decompensation of underlying disease; the risk of pain becoming chronic
(e.g. postherpetic neuralgia); the risk of herpes zoster non-pain complications;
the detrimental impact of herpes zoster on quality of life, functioning, and
mood; the therapeutic difficulties due to multimorbidity, polypharmacy, and
ageing; and the role of stressful life events in the infection itself and
comorbid depression. This model underlines the importance of early treatment,
strengthening coping, and vaccine prevention.
PMID- 26440663
TI - The N-silylation of sulfoximines.
AB - The copper-catalyzed N-silylation of sulfoximines was achieved in the presence of
di-tert-butyl peroxide. Notably, alkyl, phenyl and alkoxyl silanes were all
suitable reaction partners. Mechanistic studies revealed that N-silyl acetamide
serves as the intermediate.
PMID- 26440664
TI - A novel missense mutation in the gene EDARADD associated with an unusual
phenotype of hypohidrotic ectodermal dysplasia.
AB - Hypohidrotic ectodermal dysplasia (HED) is a rare disorder characterized by
deficient development of structures derived from the ectoderm including hair,
nails, eccrine glands, and teeth. HED forms that are caused by mutations in the
genes EDA, EDAR, or EDARADD may show almost identical phenotypes, explained by a
common signaling pathway. Proper interaction of the proteins encoded by these
three genes is important for the activation of the NF-kappaB signaling pathway
and subsequent transcription of the target genes. Mutations in the gene EDARADD
are most rarely implicated in HED. Here we describe a novel missense mutation,
c.367G>A (p.Asp123Asn), in this gene which did not appear to influence the
interaction between EDAR and EDARADD proteins, but led to an impaired ability to
activate NF-kappaB signaling. Female members of the affected family showed either
unilateral or bilateral amazia. In addition, an affected girl developed bilateral
ovarian teratomas, possibly associated with her genetic condition.
PMID- 26440665
TI - Neutralizing Antibody Response after Intramuscular Purified Vero Cell Rabies
Vaccination (PVRV) in Iranian Patients with Specific Medical Conditions.
AB - OBJECTIVE: Post exposure prophylaxis using one of the WHO-approved vaccines is
the method of choice for preventing rabies. Abnormal immune function in patients
with some specific medical conditions, such as pregnancy, chronic hepatitis B
virus infection, different types of cancers like lymphoma, diabetes I and II,
corticosteroid consumption by patients with rheumatoid arthritis and lupus
erythematosus, could impair the immunologic response to various vaccines. The
immune response to rabies vaccination has never been examined in patients with
any of these described medical conditions. This study purposed to evaluate the
neutralyzing antibody response after vaccination with purified Vero cell rabies
vaccine (PVRV) according to the WHO-recommended Post-Exposure Prophylaxis (PEP)
"ESSEN" regimen. METHODS: Thirty healthy volunteers and 50 volunteers with
different medical conditions who were exposed to a suspected rabid animal in the
2nd or 3rd category of exposure received 5 doses of PVRV under the ESSEN
protocol. Three blood samples were collected on days 0 (before the first dose),
14, and 35. The anti-rabies antibody titer was measured using the Rapid
Fluorescent Foci Inhibition Test (RFFIT) and an ELISA Bio-Rad, Platelia, Rabies
II kit. RESULTS: All subjects reached NAb titers above 0.5 IU/ml by day 14 after
vaccination. On day 35 (1 week after receiving the last rabies vaccine), anti
rabies antibodies were in the protective level (>0.5 IU/ml) in both groups. There
was no statistically significant difference in anti-rabies antibody response due
to the type of exposure (category 2 or 3), and successful seroconversion was
confirmed in both groups. CONCLUSION: In conclusion, the ESSEN protocol using the
PVRV vaccine is sufficient for rabies prophylaxis in patients with specific
medical conditions.
PMID- 26440666
TI - Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune
Encephalomyelitis Through AMPK and PPAR-gamma/ROR-gammat Signaling.
AB - Arctigenin is a herb compound extract from Arctium lappa and is reported to
exhibit pharmacological properties, including neuronal protection and
antidiabetic, antitumor, and antioxidant properties. However, the effects of
arctigenin on autoimmune inflammatory diseases of the CNS, multiple sclerosis
(MS), and its animal model experimental autoimmune encephalomyelitis (EAE) are
still unclear. In this study, we demonstrated that arctigenin-treated mice are
resistant to EAE; the clinical scores of arctigenin-treated mice are
significantly reduced. Histochemical assays of spinal cord sections also showed
that arctigenin reduces inflammation and demyelination in mice with EAE.
Furthermore, the Th1 and Th17 cells in peripheral immune organs are inhibited by
arctigenin in vivo. In addition, the Th1 cytokine IFN-gamma and transcription
factor T-bet, as well as the Th17 cytokines IL-17A, IL-17F, and transcription
factor ROR-gammat are significantly suppressed upon arctigenin treatment in vitro
and in vivo. Interestedly, Th17 cells are obviously inhibited in CNS of mice with
EAE, while Th1 cells do not significantly change. Besides, arctigenin
significantly restrains the differentiation of Th17 cells. We further demonstrate
that arctigenin activates AMPK and inhibits phosphorylated p38, in addition,
upregulates PPAR-gamma, and finally suppresses ROR-gammat. These findings suggest
that arctigenin may have anti-inflammatory and immunosuppressive properties via
inhibiting Th17 cells, indicating that it could be a potential therapeutic drug
for multiple sclerosis or other autoimmune inflammatory diseases.
PMID- 26440667
TI - Treatment of SMB-S15 Cells with Resveratrol Efficiently Removes the PrP(Sc)
Accumulation In Vitro and Prion Infectivity In Vivo.
AB - Prion diseases are transmissible and invariably fatal neurodegenerative
disorders, which still lack of efficacious prophylactic and therapeutic tools.
Our previous study has proposed that the natural phytoalexin, resveratrol, can
reduce the amounts of PrP(Sc) in a scrapie-infected cell line SMB-S15. To address
its anti-prion efficacy, the inhibitive activity of resveratrol on prion
accumulation in vitro and prion infectivity in vivo was analyzed in the present
study. Exposure of SMB-S15 cells to various concentrations of resveratrol (0.25
to 200 MUM) reduced and even removed cellular PrP(Sc) in a dose-dependent manner,
with EC50 0.61 MUM. Meanwhile, PrP(Sc) signals in SMB-S15 cells treated with 5
and 10 MUM resveratrol maintained undetectable after drug withdrawal, indicating
that the removal of PrP(Sc) in SMB-S15 cells by resveratrol is irreversible.
Furthermore, the lysates of SMB-S15 cells exposed to 10 MUM resveratrol for 2 and
7 days were intracerebrally inoculated into CD1 mice. All mice (n = 9) infected
with SMB-S15 cells without treatment of resveratrol appeared typical experimental
scrapie symptoms from 155 to 228 day post inoculation (dpi), while all mice (n =
9) inoculated with SMB-S15 cells treated with resveratrol for 7 days maintained
healthy by the end of observations (284 dpi). PrP-specific Western blots and
neuropathological tests did not identify PrP(Sc) or prion disease-associated
pathological abnormality in the brains of mice inoculated with 7-day resveratrol
treated SMB-S15 cells. It indicates that the prion infectivity of SMB-S15 onto
CD1 mice is eradicated by 1-week resveratrol treatment. Sensitivity of PrP(Sc) to
resveratrol highlights its potential role in prion therapeutics.
PMID- 26440669
TI - New clinical decision instruments can and should reduce radiation exposure.
AB - In this Perspective linked to Rodriguez and colleagues, Emmanuel Lagarde
discusses the importance of decision instruments that can help physicians avoid
subjecting patients to radiation exposure from unnecessary CT scans.
PMID- 26440668
TI - Inositol Hexakisphosphate Kinase 2 Promotes Cell Death in Cells with Cytoplasmic
TDP-43 Aggregation.
AB - TAR DNA-binding protein 43 (TDP-43) has been identified as a major component of
ubiquitin-positive inclusions in the brains and spinal cords of patients with
frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) or
amyotrophic lateral sclerosis (ALS). The phosphorylated C-terminal fragment of
TDP-43 forms aggregates in the neuronal cytoplasm, possibly resulting in neuronal
cell death in patients with FTLD-U or ALS. The inositol pyrophosphate known as
diphosphoinositol pentakisphosphate (InsP7) contains highly energetic
pyrophosphate bonds. We previously reported that inositol hexakisphosphate kinase
type 2 (InsP6K2), which converts inositol hexakisphosphate (InsP6) to InsP7,
mediates cell death in mammalian cells. Moreover, InsP6K2 is translocated from
the nucleus to the cytosol during apoptosis. In this study, we verified that
phosphorylated TDP-43 co-localized and co-bound with InsP6K2 in the cytoplasm of
anterior horn cells of the spinal cord. Furthermore, we verified that cell death
was augmented in the presence of cytoplasmic TDP-43 aggregations and activated
InsP6K2. However, cells with only cytoplasmic TDP-43 aggregation survived because
Akt activity increased. In the presence of both TDP-43 aggregation and activated
InsP6K2 in the cytoplasm of cells, the expression levels of HSP90 and casein
kinase 2 decreased, as the activity of Akt decreased. These conditions may
promote cell death. Thus, InsP6K2 could cause neuronal cell death in patients
with FTLD-U or ALS. Moreover, InsP6K2 plays an important role in a novel cell
death pathway present in FTLD-U and ALS.
PMID- 26440670
TI - Sudden onset unexplained encephalopathy in infants: think of cannabis
intoxication.
AB - The use of cannabis as both a therapeutic agent and recreational drug is common,
and its availability is increasing as a result of legalization in many countries.
Among older children, the manifestations of cannabis intoxication are numerous
and include both neurological and systemic manifestations that are frequently non
specific. There have been only a few reports detailing cannabis intoxication in
infants and toddlers. We describe three infants who presented to the emergency
department with encephalopathic signs without prominent systemic manifestations.
During the initial interview of caregivers, no history of exposure to neurotoxic
agents was obtained. All three patients were subsequently diagnosed with cannabis
intoxication based on urine toxic screens for delta-9-tetrahydrocannabinol (THC).
The infants recovered with supportive care that included fluids and monitoring.
The non-specific symptomatology of cannabis intoxication in infants together with
the wide differential for unexplained acute onset encephalopathy may delay
diagnosis and lead to inappropriate procedures and interventions such as
antimicrobial treatments and imaging studies. CONCLUSION: Healthcare personnel of
emergency rooms, urgent care centers, and general clinics should be aware of the
potential risk of cannabis ingestion in young infants. A thorough medical history
and toxic screen are warranted in all infants with unexplained decreased
sensorium.
PMID- 26440671
TI - Carbamoylphosphate synthetase 1 (CPS1) deficiency: clinical, biochemical, and
molecular characterization in Malaysian patients.
AB - Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare autosomal recessive
disorder of ureagenesis presenting as life-threatening hyperammonemia. In this
study, we present the main clinical features and biochemical and molecular data
of six Malaysian patients with CPS1 deficiency. All the patients have neonatal
onset symptoms, initially diagnosed as infections before hyperammonemia was
recognized. They have typical biochemical findings of hyperglutaminemia,
hypocitrullinemia, and low to normal urinary excretion of orotate. One neonate
succumbed to the first hyperammonemic decompensation. Five neonatal survivors
received long-term treatment consisting of dietary protein restriction and
ammonia-scavenging drugs. They have delayed neurocognitive development of varying
severity. Genetic analysis revealed eight mutations in CPS1 gene, five of which
were not previously reported. Five mutations were missense changes while another
three were predicted to create premature stop codons. In silico analyses showed
that these new mutations affected different CPS1 enzyme domains and were
predicted to interrupt interactions at enzyme active sites, disturb local enzyme
conformation, and destabilize assembly of intact enzyme complex. CONCLUSION: All
mutations are private except one mutation; p.Ile1254Phe was found in three
unrelated families. Identification of a recurrent p.Ile1254Phe mutation suggests
the presence of a common and unique mutation in our population. Our study also
expands the mutational spectrum of the CPS1 gene.
PMID- 26440672
TI - MUOrgano: A Lego(r)-Like Plug & Play System for Modular Multi-Organ-Chips.
AB - Human organ-on-a-chip systems for drug screening have evolved as feasible
alternatives to animal models, which are unreliable, expensive, and at times
erroneous. While chips featuring single organs can be of great use for both
pharmaceutical testing and basic organ-level studies, the huge potential of the
organ-on-a-chip technology is revealed by connecting multiple organs on one chip
to create a single integrated system for sophisticated fundamental biological
studies and devising therapies for disease. Furthermore, since most organ-on-a
chip systems require special protocols with organ-specific media for the
differentiation and maturation of the tissues, multi-organ systems will need to
be temporally customizable and flexible in terms of the time point of connection
of the individual organ units. We present a customizable Lego(r)-like plug & play
system, MUOrgano, which enables initial individual culture of single organ-on-a
chip systems and subsequent connection to create integrated multi-organ
microphysiological systems. As a proof of concept, the MUOrgano system was used
to connect multiple heart chips in series with excellent cell viability and
spontaneously physiological beat rates.
PMID- 26440673
TI - Nanofibrous microspheres via emulsion gelation and carbonization.
AB - Nanofibrous hydrogel microspheres are formed by pH gelation of perylene diimide
derivatives in emulsion droplets. These microspheres are freeze-dried and
subsequently carbonized to produce discrete N-doped nanofibrous carbon
microspheres. The carbon microspheres show high performance as electrode
materials for supercapacitors.
PMID- 26440674
TI - Hyperisampsins H-M, Cytotoxic Polycyclic Polyprenylated Acylphloroglucinols from
Hypericum sampsonii.
AB - Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), named
hyperisampsins H-M (1-6), were isolated from the aerial parts of Hypericum
sampsonii, together with five known analogs (7-11). The structures of 1-6 were
established by extensive spectroscopic analyses, including HRESIMS and NMR. In
addition, the absolute configurations of these new compounds were determined by
electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the
first examples of PPAPs possessing a unique gamma-lactone ring at C-23, while 3-6
differed from normal PPAPs with an unprecedented 1,2-dioxane ring. Compounds 1-7
were evaluated for their cytotoxic activities against a panel of human cancer
cell lines in vitro, of which 3, 4, and 6 exhibited significant cytotoxic
activities with IC50 values ranging from 0.56 to 3.00 MUM. Moreover, compound 3
induces leukemia cell apoptotic death, evidenced by activation of caspase-3,
degradation of PARP, up-regulation of Bax, and down-regulation of Bcl-2 and Bcl
xl.
PMID- 26440675
TI - Electronic nose analysis of exhaled breath to diagnose ventilator-associated
pneumonia.
AB - BACKGROUND: Exhaled breath analysis is an emerging technology in respiratory
disease and infection. Electronic nose devices (e-nose) are small and portable
with a potential for point of care application. Ventilator-associated pneumonia
(VAP) is a common nosocomial infection occurring in the intensive care unit
(ICU). The current best diagnostic approach is based on clinical criteria
combined with bronchoalveolar lavage (BAL) and subsequent bacterial culture
analysis. BAL is invasive, laborious and time consuming. Exhaled breath analysis
by e-nose is non-invasive, easy to perform and could reduce diagnostic time. Aim
of this study was to explore whether an e-nose can be used as a non-invasive in
vivo diagnostic tool for VAP. METHODS: Seventy-two patients met the clinical
diagnostic criteria of VAP and underwent BAL. In thirty-three patients BAL
analysis confirmed the diagnosis of VAP [BAL+(VAP+)], in thirty-nine patients the
diagnosis was rejected [BAL-]. Before BAL was performed, exhaled breath was
sampled from the expiratory limb of the ventilator into sterile Tedlar bags and
subsequently analysed by an e-nose with metal oxide sensors (DiagNose, C-it,
Zutphen, The Netherlands). From further fifty-three patients without clinical
suspicion of VAP or signs of respiratory disease exhaled breath was collected to
serve as a control group [control(VAP-]). The e-nose data from exhaled breath
were analysed using logistic regression. RESULTS: The ROC curve comparing
[BAL+(VAP+)] and [control(VAP-)] patients had an area under the curve (AUC) of
0.82 (95% CI 0.73-0.9). The sensitivity was 88% with a specificity of 66%. The
comparison of [BAL+(VAP+)] and [BAL-] patients revealed an AUC of 0.69; 95% CI
0.57-0.81) with a sensitivity of 76% with a specificity of 56%. CONCLUSION: E
nose lacked sensitivity and specificity in the diagnosis of VAP in the present
study for current clinical application. Further investigation into this field is
warranted to explore the diagnostic possibilities of this promising new
technique.
PMID- 26440676
TI - Prevalence and risk factors of COPD among never-smokers in two areas of Sweden -
Occupational exposure to gas, dust or fumes is an important risk factor.
AB - BACKGROUND: Although active tobacco smoking is the main risk factor for COPD,
COPD is not uncommon also among never-smokers. Different study locations along
with different spirometric definitions of COPD have historically yielded
different prevalence estimates of the disease. AIM: To study current prevalence
and risk factors of COPD among never-smokers in two areas of Sweden. METHODS:
Data collected in 2008-2012 within the West Sweden Asthma Study and Obstructive
Lung Disease in Northern Sweden Studies was pooled. The study population
consisted of 1839 subjects who participated in spirometry and interviews. COPD
was defined as post-bronchodilator a) FEV(1)/(F)VC < 0.7, b) FEV(1)/FVC < 0.7 and
c) FEV(1)/FVC < lower limit of normal. RESULTS: Of the 1839 subjects, 967 (52.6%)
were never-smokers. Among the never-smoking subjects, the prevalence of COPD
according to definitions a-c was 7.7%, 4.9% and 3.0%, respectively. The
corresponding prevalence of GOLD grade >=2 was 2.0%, 1.4% and 1.3%. No
significant difference in prevalence between the two study areas was observed. In
never-smokers, occupational exposure to gas, dust or fumes (GDF) was
significantly associated with both COPD (OR 1.85, 95% CI 1.03-3.33), and GOLD >=2
(OR 4.51, 1.72-11.9) according to definition a), after adjusting for age,
educational level and exposure to passive smoking at work. CONCLUSION: Depending
on definition, prevalence of COPD among never-smokers was 3.0-7.7%, whereas GOLD
>=2 was present in 1.3-2.0%. Occupational exposure to GDF remained independently
and significantly associated with COPD regardless of spirometric definition of
the disease.
PMID- 26440677
TI - Association of FTO and IRX3 genetic variants to obesity risk in north India.
AB - BACKGROUND: Obesity is an increasingly important health problem worldwide as well
as in developing countries like India. Recent genetic studies suggest that
obesity associated FTO and IRX3 are functionally linked and many effects due to
genetic variants in FTO gene act through IRX3. AIM: To evaluate the association
of FTO and IRX3 genetic variants towards obesity risk. SUBJECTS AND METHODS:
North Indian individuals categorised as non-obese (BMI < 30 kg/m(2)) and obese
(BMI >= 30 kg/m(2)) were selected. FTO rs8050136, rs1421085, rs9939609,
rs17817449 and IRX3 rs3751723 were genotyped by means of validated Taqman(r)
allelic discrimination to evaluate their association with obesity by means of
single locus logistic regression by SPSS ver. 19 and multi-locus linkage and
haplotype analysis by SNPStats and gene-gene interaction with Generalised
Multifactor Dimensionality Reduction (GMDR) ver.6. RESULTS: In single locus
analysis, FTO rs8050136 CA (p = 0.0001; OR (95% CI) = 2.4 (1.7-3.4) and AA (p =
0.0001; OR (95% CI) = 3.1 (1.9-5.2); FTO rs1421085 TA (p = 0.0001; OR (95% CI) =
2.1 (1.4-3.0) and AA (p = 0.0001; OR (95% CI) = 3.0 (1.8-5.0); FTO rs9939609 TC
(p = 0.0001; OR (95% CI) = 2.1 (1.5-3.1) and CC (p = 0.0001; OR (95% CI) = 4.2
(2.5-7.3) along with TG (p = 0.001; OR (95% CI) = 2.1 (1.3-3.2) and GG (p =
0.021; OR (95% CI) = 3.8 (1.2-11.8) genotypes of FTO rs17817449 with GT (p =
0.0001; OR (95% CI) = 2.1 (1.5-3.1) and TT (p = 0.012; OR (95% CI) = 3.3 (1.8
3.6) genotypes of IRX3 rs3751723 were significantly associated with obesity. In
multi-locus analysis, SNPs of FTO and IRX3 were in strong linkage disequilibrium
and in haplotype and GMDR analysis the SNPs were significantly associated with
obesity risk (p < 0.05). CONCLUSION: This is the first study to reveal that
genetic variants of both FTO and IRX3 genes are in high linkage disequilibrium
(LD) and are associated with obesity risk in North Indians.
PMID- 26440678
TI - Analysis of the Interobserver Variability in Penile Length Assessment.
AB - INTRODUCTION: Many men seek penile augmentation treatments-a standard tool for
their counseling is to inform them of what is "normal." Although some studies
suggest good correlation between stretched and erect penile length, those that
have measured stretched and erect length simultaneously have shown significant
variability. AIM: To assess the accuracy of differing penile measurements with
multiple observers. METHODS: We recruited 201 adult men (mean age 49.6 years) who
achieved full erection using intracavernosal injection. MAIN OUTCOME MEASURES:
Penile measurements were taken by one of seven andrology specialists in a
private, temperature-controlled (21 degrees C, 72 degrees F) environment.
Stretched flaccid and erect length and circumference were measured. We analyzed
the accuracy of each flaccid measurement using the erect measurements as a
reference, for the overall patient population and for each observer. RESULTS: The
mean underestimate of length from stretched flaccid to erect was 2.64 cm (21.4%)
and girth 2.27 cm (19.5%). Interobserver variability ranged from a mean
underestimate of 16-27% (length) and 15-27% (girth). CONCLUSIONS: In this large,
multicenter, multi-observer study of penis size, flaccid measurements
underestimated erect size. It also seems likely that there is significant
interobserver variability. We believe erect penis measurements should be used for
men being considered for treatment of small penis anxiety.
PMID- 26440679
TI - [Diagnosis and treatment of esophagogastric junction cancer].
PMID- 26440680
TI - [Endoscopic diagnosis and treatment for carcinoma of the esophagogastric
junction].
PMID- 26440681
TI - [Surgery for esophagogastric junction tumor].
PMID- 26440683
TI - [Not Available].
PMID- 26440682
TI - [Multidisciplinary therapy for esophagogastric junction cancer].
PMID- 26440684
TI - [Adherence to oral 5-aminosalicylic acid by patients with quiescent ulcerative
colitis: a questionnaire survey].
AB - For patients with ulcerative colitis, adherence to 5-aminosalicylic acid (5-ASA)
is generally expected to ensure better maintenance of remission. Over the past 2
years, we have conducted a questionnaire survey in our hospital of 120
outpatients with quiescent ulcerative colitis to assess their adherence to oral 5
ASA. Of them, 112 patients responded. The overall adherence rate was 57%;
however, the adherence rate for 5-ASA taken once a day was 95%, which was
significantly higher than that for 5-ASA taken twice or three times a day (50%;
P=0.00044). Univariate analysis revealed that the factors associated with high
adherence included the following: type of 5-ASA derivative, intake of fewer drugs
being at a time, and once-daily intake of 5-ASA. However, once-daily intake of 5
ASA was the only factor found to have a statistically significant effect using
multivariate analysis. The adherence rate improved from 23% to 100% when the
prescription for 5-ASA was changed from two or three times daily to once daily
(P=0.000054).
PMID- 26440685
TI - [Rupture of a gastroduodenal artery aneurysm caused by duodenal ulcer: a case
report].
AB - A 73-year-old man with a history of tarry stools was admitted to our hospital.
Gastroduodenoscopy on admission revealed an ulcer with an exposed vessel at the
duodenal bulb. During endoscopic clipping for prevention of re-bleeding, a large
amount of bleeding from the vessel was observed. Hemostasis was achieved after
the procedure. However, 7 days later, the patient passed a large amount of tarry
stools and experienced hypovolemic shock. Endoscopic re-examination revealed a
pulsatile aneurysmal vessel at the base of the duodenal ulcer. Abdominal contrast
enhanced computed tomography and abdominal angiography demonstrated an aneurysm
of the gastroduodenal artery, which was successfully treated with transcatheter
arterial embolization. Thus, here we report a rare case of an aneurysm of the
gastroduodenal artery caused by a duodenal ulcer.
PMID- 26440686
TI - [Endoscopic nasobiliary and nasopancreatic drainage contributing to healing of
duodenal ulcer perforation: a case report].
AB - A 75-year-old man with vomiting and right abdominal pain was admitted to the
Department of Surgery in our hospital. With a diagnosis of perforated duodenal
ulcer, he was treated conservatively. On the day 8 of hospitalization, his
general condition worsened and he underwent surgery. During operation, the
perforated duodenal ulcer and paraduodenal fluid collection was observed, and
percutaneous drainage was accordingly established. After this procedure, renal
dysfunction was exacerbated and he was transferred to our department for
endoscopic treatment. On day 28 of hospitalization, nasobiliary and
nasopancreatic drainage was administered. Renal dysfunction gradually improved,
and healing of the perforated duodenal ulcer was recognized on day 93. On day
112, the patient was discharged.
PMID- 26440687
TI - [A case of acquired immunodeficiency syndrome with ileocecal ulcer].
AB - We report a case of a patient with acquired immunodeficiency syndrome (AIDS) and
ileocecal ulcer. A 31-year-old man was admitted with chief complaints of
decreased body weight and abdominal pain. Colonoscopy revealed a round punched
out ulcer on the ileocecal valve. Initially, we suspected entero-Behcet's disease
and simple ulcer as the cause of the ileocecal ulcer. However, after histologic
examination of tissue biopsies obtained during colonoscopy, we diagnosed the
patient as having cytomegalovirus (CMV) enteritis. Based on the patient's white
blood cell depletion and CMV enteritis, we performed a human immunodeficiency
virus (HIV) antibody test. The test was positive, and the diagnosis of AIDS was
established. The number of patients with AIDS has been increasing in Japan; thus,
we should consider the possibility of CMV enteritis and AIDS in young adult
patients affected by ileocecal ulcer with no notable history.
PMID- 26440688
TI - [IgA vasculitis associated with anti-TNF-alpha inhibitors in a patient with
Crohn's disease].
AB - Anti-TNF-alpha inhibitors have been widely used in the treatment of inflammatory
bowel disease. Although they have good clinical efficacy and tolerance, they
remain a matter of concern because they cause drug-induced autoimmune disorders
as side effects. Here, we report a case of a patient with Crohn's disease who
developed IgA vasculitis after infliximab and adalimumab treatment. A 17-year-old
male with Crohn's disease who had received scheduled infliximab treatment for the
preceding 19 months complained of purpura on his lower limbs. He was diagnosed
with infliximab-induced IgA vasculitis. Switching infliximab to adalimumab
resulted in rapid improvement of the condition. However, 21 months after
switching to adalimumab, his purpura recurred. Drug-induced IgA vasculitis is a
rare complication caused by infliximab and adalimumab; however, diagnosis in the
early phase and appropriate management of patients receiving anti-TNF-alpha
inhibitors is critical to a successful patient outcome.
PMID- 26440689
TI - [A case of epidermoid cyst in an intrapancreatic accessory spleen showing cyst-in
cyst-like structure mimicking mucinous cystic neoplasm].
AB - In 2010, a 39-year-old woman presented with a cystic lesion, 16 mm in diameter,
in the tail of the pancreas. Regular follow-ups were conducted to monitor this
lesion; its diameter was found to increase to 45 mm in 2013. Thus, the patient
was admitted to our hospital for further examination and treatment. Abdominal US,
abdominal contrast-enhanced CT, and MRI showed a cystic lesion of 45 mm in
diameter in the tail of the pancreas, which had internal septae and mural nodules
inside. EUS revealed a cyst-in-cyst-like structure, with a thickened cystic wall
along the entire circumference. Thus, distal pancreatectomy and splenectomy were
performed on the basis of a diagnosis of mucinous cystic neoplasm.
Histopathological examination of a resected specimen showed that the lesion
comprised a substantial component of red-brown tone, with adjacent cystic
components. The final diagnosis was an epidermoid cyst in an intrapancreatic
accessory spleen.
PMID- 26440690
TI - A barrier retractor to reduce surgical site infections and wound disruptions in
obese patients undergoing cesarean delivery: a randomized controlled trial.
AB - BACKGROUND: Surgical site infections (SSIs) are an important cause of morbidity
following cesarean delivery, particularly in obese patients. Methods to reduce
SSIs after cesarean delivery would have an important impact in obese obstetric
patients. OBJECTIVE: The purpose of this study was to determine whether the
Alexis O cesarean delivery retractor, a barrier self-retaining retractor, reduces
SSIs and wound disruptions in obese patients undergoing cesarean delivery. STUDY
DESIGN: This was a randomized controlled trial of obese women (body mass index >=
30 kg/m(2)) undergoing nonemergent cesarean delivery. Patients were randomized to
the treatment group (using the Alexis O cesarean delivery retractor) or to the
control group (using conventional handheld retractors). The primary outcome was
SSI or wound disruption during the 30 day postoperative period. Secondary
outcomes included operative time, estimated blood loss, change in hemoglobin,
antiemetic use, length of postoperative hospital stay, hospital readmission, and
other postoperative complications. RESULTS: A total of 301 patients were enrolled
in the study. One hundred forty-four patients were randomized to the treatment
group and 157 to the control group. Baseline characteristics and indications for
cesarean delivery were similar between the 2 groups. Median body mass index was
40.1 kg/m(2). There were no significant differences between the treatment and the
control group in the primary outcome of SSI or wound disruption rates at the 30
day assessment (20.6% vs 17.6%, P = .62), during the postoperative inpatient
hospitalization or at the 1-2 week postoperative visit. There were also no
differences in the primary outcome when adjusting for obesity class or thickness
of the subcuticular layer. Patients in the treatment group had lower rates of
uterine exteriorization (54.3% vs 87.3%, P < .001), but there were no differences
in all other outcomes. CONCLUSION: Use of the Alexis retractor in cesarean
delivery deliveries did not decrease SSI or wound disruption rates in an obese
population. Its use as a retractor should be left to the discretion of the
surgeon and clinical circumstances.
PMID- 26440692
TI - Long-term neurofunctional outcome, executive functioning, and behavioral adaptive
skills following fetal myelomeningocele surgery.
AB - BACKGROUND: Myelomeningocele (MMC) represents the first nonlethal anomaly to be
treated by prenatal intervention. Case series and a prospective, randomized study
show that fetal surgery for MMC before 26 weeks' gestation may preserve
neurological function. Long-term follow-up is a fundamental component to evaluate
the overall efficacy of any new medical or surgical procedure. To further
delineate the long-term impact of fMMC surgery, we continued to follow children
treated in our institution before the Management of Myelomeningocele Study trial
by the means of parental questionnaires to assess changes in functional,
developmental, and cognitive status as these unique patients grow older.
OBJECTIVE: The objective of the study was to evaluate the long-term neurological
outcome, executive functioning (EF), and behavioral adaptive skills (BAS)
following fetal myelomeningocele (fMMC) surgery. STUDY DESIGN: Prior to the
Management of Myelomeningocele Study trial, 54 patients underwent fMMC surgery at
our institution. Parents of 42 children (78%) participated in structured
questionnaires focusing on neurofunctional outcome. EF and BAS were measured by
the Behavior Rating Inventory of Executive Function (BRIEF) and the Adaptive
Behavioral Assessment System II. The BRIEF is organized into 3 primary indices
including the following: Global Executive Composite, Metacognition Index, and
Behavioral Regulation Index. The Adaptive Behavioral Assessment System II results
in a general adaptive composite score. Based on SD intervals, EF and BAS were
categorized as being average, borderline, or impaired. RESULTS: At a median
follow-up age of 10 years (range, 8-14 years), 33 (79%) are community ambulators,
3 (9%) are household ambulators, and 6 (14%) are wheelchair dependent. Preschool
ambulation was predictive of long-term ambulation (P < .01), whereas the need for
tethered cord surgery was associated with persistent deterioration of ambulatory
status (P = .007). Normal bladder function was found in 26%. Although the
majority scored within the average range for the Behavioral Regulation Index,
Metacognition Index, and Global Executive Composite indices, significantly more
children who had fMMC surgery had deficits in EF in all 3 BRIEF indices compared
with the population norms. The general adaptive composite scores were also more
likely to fall below average following fMMC surgery. Normal early
neurodevelopmental outcomes were predictive of normal EF and BAS (P < .01). Need
for shunting was associated with a significant impairment of BAS (P = .02).
CONCLUSION: The present study suggests that fMMC surgery improves long-term
functional outcome. The majority of fMMC children can successfully complete
everyday tasks at home and at school. Abnormalities of BAS appear to be more
common than impairments in EF and therefore offer an area for early screening and
interventional therapy for these at-risk children. Non-shunted fMMC children with
normal early neurodevelopmental outcome are less likely to experience problems
with EF and BAS. fMMC surgery improves long-term ambulatory status. Symptomatic
spinal cord tethering with or without intradural inclusion cyst is associated
with functional loss. More than expected fMMC children are continent, but bowel
and bladder control continue to be an ongoing challenge for the fMMC children.
PMID- 26440691
TI - A risk of waiting: the weekly incidence of hypertensive disorders and associated
maternal and neonatal morbidity in low-risk term pregnancies.
AB - BACKGROUND: Elective induction of labor (eIOL) prior to 39 weeks' gestation is
discouraged because of presumed fetal benefits. However, few data exist on the
maternal risks of expectant management. To date, no study has evaluated the
maternal risk of developing a hypertensive disorder of pregnancy with expectant
management of a low-risk gravid at term. OBJECTIVE: We sought to evaluate the
development of hypertensive disorders in term low-risk expectantly managed
patients. STUDY DESIGN: This is a retrospective cross-sectional study from 19 US
hospitals, from 2002 to 2008 (Safe Labor Consortium) including all nonanomalous,
cephalic, singleton pregnancies at 37-41 weeks. Women with a history of
hypertension, diabetes mellitus, cardiovascular disease, or planned cesarean
delivery or from centers with incomplete hypertensive data were excluded. Women
with eIOL in each week were compared with women managed expectantly until the
next week of gestation or beyond. The primary outcome was the frequency of
hypertensive complications. RESULTS: Of 114,651 low-risk deliveries, 12,772
(11.1%) had eIOL. The cohort was 49.2% nulliparous, 51.1% white, and obese (mean
body mass index 30.2 kg/m(2)). The risk of developing any hypertension in
expectantly managed women was 4.1% after 37 weeks, 3.5% after 38 weeks, 3.2%
after 39 weeks, and 2.6% after 40 weeks. Compared with eIOL, women with
hypertensive disorders had significantly higher rates of cesarean delivery and
maternal morbidities (intensive care unit admission or death, third- or fourth
degree lacerations, maternal infections, and bleeding complications) at each week
of gestation and the composite neonatal morbidity at 38 and 39 weeks of
gestation. CONCLUSION: For women at low risk expectantly managed at term, there
is a risk of developing hypertensive complications for each additional week of
pregnancy, with associated increases in maternal and neonatal morbidities.
PMID- 26440693
TI - Genome-wide linkage and exome sequencing analyses identify an initiation codon
mutation of KRT5 in a unique Chinese family with generalized Dowling-Degos
disease.
PMID- 26440694
TI - Nitrene Insertion into C-C and C-H Bonds of Diamide Diimine Ligands Ligated to
Chromium and Iron.
AB - The impact of redox non-innocence (RNI) on chemical reactivity is a forefront
theme in coordination chemistry. A diamide diimine ligand, [{-CH=N(1,2
C6H4)NH(2,6-iPr2C6H3)}2](n) (n = 0 to -4), (dadi)(n), chelates Cr and Fe to give
[(dadi)M] ([1Cr(thf)] and [1Fe]). Calculations show [1Cr(thf)] (and [1Cr]) to
have a d(4) Cr configuration antiferromagnetically coupled to (dadi)(2-)*, and
[1Fe] to be S = 2. Treatment with RN3 provides products where RN is formally
inserted into the C-C bond of the diimine or into a C-H bond of the diimine.
Calculations on the process support a mechanism in which a transient imide
(imidyl) aziridinates the diimine, which subsequently ring opens.
PMID- 26440695
TI - Proximal humerus fragility fractures: recent trends in nonoperative and operative
treatment in the Medicare population.
AB - BACKGROUND: With an aging population, fragility fractures including injuries to
the proximal humerus continue to rise in the United States. The purpose of this
study was to investigate recent trends in the incidence and treatment of proximal
humerus fractures (PHFs) in a cross-sectional elderly population. METHODS:
Medicare data from 2005 to 2012 were queried to identify patients treated for
PHF. Associated patient demographics, hospitalization data, treatment, and
revision status were obtained. Statistical analyses were performed to identify
significant trends in treatment. RESULTS: There were 259,506 PHFs recorded, with
79% occurring in female patients. In all age groups, nonoperative treatment of
PHF was the most common method (67%). Within the surgical group, open reduction
with internal fixation was most frequently used, and total shoulder arthroplasty
(TSA) or reverse total shoulder arthroplasty (RTSA) was the least common (11%).
However, although the overall rate of surgical intervention remained constant,
there was a significant increase in treatment with TSA from 3% in 2005 to 17% in
2012. In particular, RTSA represented 89% of all TSAs for PHF in 2011. All
surgical treatment options demonstrated high 2-year survival rates without
revision surgery (97%). CONCLUSION: Recent trends show that in the elderly
population, nonoperative management remains the most common treatment for PHFs.
Within the surgically treated cohort, there has been an increase in treatment
with arthroplasty including RTSA, with a low rate of early revisions. There are
excellent survival rates in all surgically treated PHFs, but long-term data will
be required to fully evaluate the viability of these surgical options.
PMID- 26440696
TI - Computer algorithms for three-dimensional measurement of humeral anatomy:
analysis of 140 paired humeri.
AB - BACKGROUND: In the presence of severe osteoarthritis, osteonecrosis, or proximal
humeral fracture, the contralateral humerus may serve as a template for the 3
dimensional (3D) preoperative planning of reconstructive surgery. The purpose of
this study was to develop algorithms for performing 3D measurements of the
humeral anatomy and further to assess side-to-side (bilateral) differences in
humeral head retrotorsion, humeral head inclination, humeral length, and humeral
head radius and height. METHODS: The 3D models of 140 paired humeri (70 cadavers)
were extracted from computed tomographic data. Geometric characteristics
quantifying the humeral anatomy in 3D were determined in a semiautomatic fashion
using the developed computer algorithms. The results between the sides were
compared for evaluating bilateral differences. RESULTS: The mean bilateral
difference of the humeral retrotorsion angle was 6.7 degrees (standard deviation
[SD], 5.7 degrees ; range, -15.1 degrees to 24.0 degrees ; P = .063); the mean
side difference of the humeral head inclination angle was 2.3 degrees (SD, 1.8
degrees ; range, -5.1 degrees to 8.4 degrees ; P = .12). The side difference in
humeral length (mean, 2.9 mm; SD, 2.5 mm; range, -8.7 mm to 10.1 mm; P = .04) was
significant. The mean side difference in the head sphere radius was 0.5 mm (SD,
0.6 mm; range, -3.2 mm to 2.2 mm; P = .76), and the mean side difference in
humeral head height was 0.8 mm (SD, 0.6 mm; range, -2.4 mm to 2.4 mm; P = .44).
CONCLUSIONS: The contralateral anatomy may serve as a reliable reconstruction
template for humeral length, humeral head radius, and humeral head height if it
is analyzed with 3D algorithms. In contrast, determining humeral head
retrotorsion and humeral head inclination from the contralateral anatomy may be
more prone to error.
PMID- 26440697
TI - Application of neural network method to detect type of uranium contamination by
estimation of activity ratio in environmental alpha spectra.
AB - The discrimination of the composition of environmental and non-environmental
materials by the estimation of the (234)U/(238)U activity ratio in alpha-particle
spectrometry is important in many applications. If the interfering elements are
not completely separated from the uranium, they can interfere with the
determination of (234)U. Thickness as a result of the existence of iron in the
source preparation phase and their alpha lines can broaden the alpha line of
(234)U in alpha spectra. Therefore, the asymmetric broadening of the alpha line
of (234)U and overlapping of peaks make the analysis of the alpha particle
spectra and the interpretation of the results difficult. Applying Artificial
Neural Network (ANN) to a spectrometry system is a good idea because it
eliminates limitations of classical approaches by extracting the desired
information from the input data. In this work, the average of a partial uranium
raw spectrum, were considered. Each point that its slope was of the order of 0-1%
per 10 channels, was used as input to the multi-layer feed forward error-back
propagation network. The network was trained by an alpha spectrum library which
has been developed in the present work. The training data in this study was
actual spectral data with any reasonable thickness and interfering elements.
According to the results, the method applied to estimate the activity ratio in
this work, can examine the alpha spectrum for peaks which would not be expected
for a source of given element and provide the clues about composition of uranium
contamination in the environmental samples in a fast screening and classifying
procedures.
PMID- 26440698
TI - Radioiodine in the atmosphere after the Fukushima Dai-ichi nuclear accident.
AB - About 160 PBq of (131)I was released into the atmosphere during the accident at
the Fukushima Dai-ichi Nuclear Power Plant. The chemistry of radioiodine is
complicated, and it can be released in several different forms. In addition, the
different physical forms, like molecular iodine, aerosol-form iodine, or organic
iodine, would have all behaved differently once in the atmosphere, and would have
been removed at different rates. These releases were detected by monitoring
stations throughout Japan, and from these measurements, key insights can be made
about the different chemical forms that were released, as well as the persistence
of each in the environment.
PMID- 26440699
TI - Spatial trends on an ungrazed West Cumbrian saltmarsh of surface contamination by
selected radionuclides over a 25 year period.
AB - Long term spatial and temporal variations in radionuclide activity have been
measured in a contaminated ungrazed saltmarsh near Ravenglass, Cumbria. Over a
twenty-five year period there has been a decrease in activity concentration with
(106)Ru and (137)Cs showing the highest rate of change followed by Pu alpha and
(241)Am. A number of factors contribute to the reduction with time; including
radiological half lives, discharge and remobilisation. For (241)Am the lower
reduction rate is partially due to ingrowth from (241)Pu and partially as a
result of transport of sediment from the offshore Irish Sea mud patch.
Considerable spatial variation for the different radionuclides was observed,
which with time became less defined. The highest activity concentrations of long
lived radionuclides were in low energy areas, typically where higher rates of
sedimentation and vegetation occurred. The trend was reversed for the shorter
lived radionuclide, (106)Ru, with higher activity concentrations observed in high
energy areas where there was frequent tidal inundation. Surface scrape samples
provide a pragmatic, practical method of measuring sediment contamination over
large areas and is a sampling approach adopted by most routine environmental
monitoring programs, but it does not allow for interpretation of the effect of
variation in sedimentation rates. This paper proposes a method for calculating
indicative sedimentation rates across the saltmarsh using surface scrape data,
which produces results consistent with values experimentally obtained.
PMID- 26440700
TI - Topologically robust sound propagation in an angular-momentum-biased graphene
like resonator lattice.
AB - Topological insulators do not allow conduction in the bulk, yet they support edge
modes that travel along the boundary only in one direction, determined by the
carried electron spin, with inherent robustness to defects and disorder.
Topological insulators have inspired analogues in photonics and optics, in which
one-way edge propagation in topologically protected two-dimensional materials is
achieved breaking time-reversal symmetry with a magnetic bias. Here, we introduce
the concept of topological order in classical acoustics, realizing robust
topological protection and one-way edge propagation of sound in a suitably
designed resonator lattice biased with angular momentum, forming the acoustic
analogue of a magnetically biased graphene layer. Extending the concept of an
acoustic nonreciprocal circulator based on angular-momentum bias, time-reversal
symmetry is broken here using moderate rotational motion of air within each
element of the lattice, which takes the role of the electron spin in determining
the direction of modal edge propagation.
PMID- 26440701
TI - Beyond Genomics: Multidimensional Analysis of Cancer Therapy Resistance.
AB - Cancer resistance to therapy occurs through a selection process generally thought
to be driven by mutations. In a recent study, Hugo et al. use multidimensional
analysis of the dynamic genetic, transcriptional, epigenetic, and immune
landscape alterations in baseline and MAPK inhibitor-resistant melanoma tumors,
demonstrating a role for 'non-genomic' drivers in cancer evolution.
PMID- 26440702
TI - Efficient Gene Editing in Primary Human T Cells.
AB - Recent advances in T-cell therapy for cancer, viral infections, and autoimmune
diseases highlight the broad therapeutic potential of T-cell engineering.
However, site-specific genetic manipulation in primary human T cells remains
challenging. Two recent studies describe efficient genome editing in T cells
using CRISPR and TALEN approaches.
PMID- 26440703
TI - Gestational diabetes mellitus in women with multiple pregnancies: is the
metabolic abnormality milder?
AB - OBJECTIVE: We aimed to compare maternal characteristics and dysglycemia after
delivery in women with gestational diabetes mellitus (GDM) according to pregnancy
being multiple (MP) or singleton (SP). The hypothesis was that women with GDM and
MP would have a milder glycemic abnormality before and after pregnancy than those
with SP. METHODS: We performed a cohort study of 2908 women giving birth between
1986 and 2009. Logistic regression was performed to discriminate between MP and
SP after anamnestic pre-pregnancy characteristics. Kaplan-Meier and Cox
regression analyses were performed to assess if MP was independently associated
with both impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and
diabetes after delivery. RESULTS: Family history of diabetes was the only
independent anamnestic pre-pregnancy characteristic discriminating MP versus SP,
OR 2.04 (95% CI 1.12, 3.70, p 0.019). The median time to progress to IFG/IGT was
7.52 years in SP (95% CI 6.92, 8.13) and 7.41 in MP (95% CI 3.84, 10.98), ns and
the progression to DM did not differ. In addition, MP was not associated to
IFG/IGT or to DM in the Cox regression analysis. CONCLUSIONS: In this cohort of
women with GDM, those with MP did not demonstrate a lesser degree of dysglycemia
after controlling for other pregnancy characteristics and pregnancy-independent
factors.
PMID- 26440704
TI - Comprehending and Rehabilitating Roman Catholic Clergy Offenders of Child Sexual
Abuse.
AB - Many have studied Roman Catholic clergy who have sexually abused children, but
the range of investigations remains disconnected. This article brings together
various disciplinary perspectives to form a comprehensive view. A review of the
literature is first undertaken to comprehend how clergy offenders have been
conceptualized in psychosocial, sociocultural, and moral-religious studies. These
perspectives are then used as a foundation for examining how these clergy can be
rehabilitated. Three rehabilitative modalities--psychological treatment,
rehabilitation through restorative justice, and ritual healing--are explored. The
article concludes with a discussion of the insights gained from the literature
review and how the modalities can be advanced in an interdependent and considered
approach.
PMID- 26440705
TI - Gyroscopic sensing in the wings of the hawkmoth Manduca sexta: the role of sensor
location and directional sensitivity.
AB - The wings of the hawkmoth Manduca sexta are lined with mechanoreceptors called
campaniform sensilla that encode wing deformations. During flight, the wings
deform in response to a variety of stimuli, including inertial-elastic loads due
to the wing flapping motion, aerodynamic loads, and exogenous inertial loads
transmitted by disturbances. Because the wings are actuated, flexible structures,
the strain-sensitive campaniform sensilla are capable of detecting inertial
rotations and accelerations, allowing the wings to serve not only as a primary
actuator, but also as a gyroscopic sensor for flight control. We study the
gyroscopic sensing of the hawkmoth wings from a control theoretic perspective.
Through the development of a low-order model of flexible wing flapping dynamics,
and the use of nonlinear observability analysis, we show that the rotational
acceleration inherent in wing flapping enables the wings to serve as gyroscopic
sensors. We compute a measure of sensor fitness as a function of sensor location
and directional sensitivity by using the simulation-based empirical observability
Gramian. Our results indicate that gyroscopic information is encoded primarily
through shear strain due to wing twisting, where inertial rotations cause
detectable changes in pronation and supination timing and magnitude. We solve an
observability-based optimal sensor placement problem to find the optimal
configuration of strain sensor locations and directional sensitivities for
detecting inertial rotations. The optimal sensor configuration shows parallels to
the campaniform sensilla found on hawkmoth wings, with clusters of sensors near
the wing root and wing tip. The optimal spatial distribution of strain
directional sensitivity provides a hypothesis for how heterogeneity of
campaniform sensilla may be distributed.
PMID- 26440706
TI - p53-based strategy to reduce hematological toxicity of chemotherapy: A proof of
principle study.
AB - p53 activation is a primary mechanism underlying pathological responses to DNA
damaging agents such as chemotherapy and radiotherapy. Our recent animal studies
showed that low dose arsenic (LDA)-induced transient p53 inhibition selectively
protected normal tissues from chemotherapy-induced toxicity. Study objectives
were to: 1) define the lowest safe dose of arsenic trioxide that transiently
blocks p53 activation in patients and 2) assess the potential of LDA to decrease
hematological toxicity from chemotherapy. Patients scheduled to receive minimum 4
cycles of myelosuppressive chemotherapy were eligible. For objective 1, dose
escalation of LDA started at 0.005 mg/kg/day for 3 days. This dose satisfied
objective 1 and was administered before chemotherapy cycles 2, 4, and 6 for
objective 2. p53 level in peripheral lymphocytes was measured on day 1 of each
cycle by ELISA assay. Chemotherapy cycles 1, 3, and 5 served as the baseline for
the subsequent cycles of 2, 4, and 6 respectively. If p53 level for the
subsequent cycle was lower (or higher) than the baseline cycle, p53 was defined
as "suppressed" (or "activated") for the pair of cycles. Repeated measures linear
models of CBC in terms of day, cycle, p53 activity and interaction terms were
used. Twenty-six patients treated with 3 week cycle regimens form the base of
analyses. The mean white blood cell, hemoglobin and absolute neutrophil counts
were significantly higher in the "suppressed" relative to the "activated" group.
These data support the proof of principle that suppression of p53 could lead to
protection of bone marrow in patients receiving chemotherapy. This trial is
registered in ClinicalTrials.gov. Identifier: NCT01428128.
PMID- 26440712
TI - Synthesis and characterization of barium silicide (BaSi2) nanowire arrays for
potential solar applications.
AB - In order to utilize nanostructured materials for potential solar and other energy
harvesting applications, scalable synthetic techniques for these materials must
be developed. Herein we use a vapor phase conversion approach to synthesize
nanowire (NW) arrays of semiconducting barium silicide (BaSi2) in high yield for
the first time for potential solar applications. Dense arrays of silicon NWs
obtained by metal-assisted chemical etching were converted to single-crystalline
BaSi2 NW arrays by reacting with Ba vapor at about 930 degrees C. Structural
characterization by X-ray diffraction and high-resolution transmission electron
microscopy confirm that the converted NWs are single-crystalline BaSi2. The
optimal conversion reaction conditions allow the phase-pure synthesis of BaSi2
NWs that maintain the original NW morphology, and tuning the reaction parameters
led to a controllable synthesis of BaSi2 films on silicon substrates. The optical
bandgap and electrochemical measurements of these BaSi2 NWs reveal a bandgap and
carrier concentrations comparable to previously reported values for BaSi2 thin
films.
PMID- 26440707
TI - Sensitivity of plasma BRAFmutant and NRASmutant cell-free DNA assays to detect
metastatic melanoma in patients with low RECIST scores and non-RECIST disease
progression.
AB - Melanoma lacks a clinically useful blood-based biomarker of disease activity to
help guide patient management. To determine whether measurements of circulating,
cell-free, tumor-associated BRAF(mutant) and NRAS(mutant) DNA (ctDNA) have a
higher sensitivity than LDH to detect metastatic disease prior to treatment
initiation and upon disease progression we studied patients with unresectable
stage IIIC/IV metastatic melanoma receiving treatment with BRAF inhibitor therapy
or immune checkpoint blockade and at least 3 plasma samples obtained during their
treatment course. Levels of BRAF(mutant) and NRAS(mutant) ctDNA were determined
using droplet digital PCR (ddPCR) assays. Among patients with samples available
prior to treatment initiation ctDNA and LDH levels were elevated in 12/15 (80%)
and 6/20 (30%) (p = 0.006) patients respectively. In patients with RECIST scores
<5 cm prior to treatment initiation, ctDNA levels were elevated in 5/7 (71%)
patients compared to LDH which was elevated in 1/13 (8%) patients (p = 0.007).
Among all disease progression events the modified bootstrapped sensitivities for
ctDNA and LDH were 82% and 40% respectively, with a median difference in
sensitivity of 42% (95% confidence interval, 27%-58%; P < 0.001). In addition,
ctDNA levels were elevated in 13/16 (81%) instances of non-RECIST disease
progression, including 10/12 (83%) instances of new brain metastases. In
comparison LDH was elevated 8/16 (50%) instances of non-RECIST disease
progression, including 6/12 (50%) instances of new brain metastases. Overall,
ctDNA had a higher sensitivity than LDH to detect disease progression, including
non-RECIST progression events. ctDNA has the potential to be a useful biomarker
for monitoring melanoma disease activity.
PMID- 26440713
TI - Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of
melatonin on glucose tolerance in humans.
AB - AIMS: The common MTNR1B genetic variant rs10830963 is associated with an
increased risk of type 2 diabetes (T2D). To date, no experimental study has
tested the effect of the MTNR1B variant on glucose metabolism in humans during
exposure of the melatonin receptors to their ligand. The aim of this study was to
investigate whether this MTNR1B variant influenced the effect of melatonin (5mg)
on glucose tolerance assessed by an oral glucose tolerance test (OGTT; 75 g) at
different times of the day (morning and evening) as compared to a placebo.
METHODS: Seventeen normoglycemic women (24 +/- 6 years; BMI 23.0 +/- 3.3 kg/m(2))
completed the study (11 carriers of the risk allele [CG] and 6 noncarriers [CC]).
RESULTS: The effect of melatonin on glucose tolerance depended on the genotype.
In the morning, the effect of melatonin (melatonin-placebo) on the glucose area
under the curve (AUC) above baseline differed significantly (P=0.036) between the
carriers and noncarriers. This effect of melatonin in the carriers was six times
as large as that in the noncarriers. The MTNR1B SNP explained over one-quarter
(26%) of the inter-individual differences in the effect of melatonin on glucose
AUC. However, in the evening, the effect of melatonin on glucose AUC of the
carriers and noncarriers did not differ significantly (P>0.05). CONCLUSIONS:
MTNR1B rs10830963 risk variant worsens the effect of melatonin on glucose
tolerance, suggesting the importance of genotyping and personalized
recommendations, especially in people consuming food when melatonin levels are
elevated. Large-scale studies in vulnerable populations are necessary to
translate these results into real-world, clinically relevant recommendations.
PMID- 26440715
TI - Involvement of sinoaortic afferents in renal sympathoinhibition and vasodilation
induced by acute hypernatremia.
AB - Despite the abundance of evidence that supports the important role of aortic and
carotid afferents to short-term regulation of blood pressure and detection of
variation in the arterial PO2 , PCO2 and pH, relatively little is known regarding
the role of these afferents during changes in the volume and composition of
extracellular compartments. The present study sought to determine the involvement
of these afferents in the renal vasodilation and sympathoinhibition induced by
hypertonic saline (HS) infusion. Sinoaortic-denervated and sham male Wistar rats
were anaesthetised with intravenous (i.v.) urethane (1.2 g/kg body weight (bw))
prior to the measurement of the mean arterial pressure (MAP), renal vascular
conductance (RVC) and renal sympathetic nerve activity (RSNA). In the sham group,
the HS infusion (3 mol/L NaCl, 1.8 mL/kg bw, i.v.) induced transient hypertension
(12 +/- 4 mmHg from baseline, peak at 10 min; P < 0.05), an increase in RVC (127
+/- 9% and 150 +/- 13% from baseline, at 20 and 60 min respectively; P < 0.05)
and a decrease in RSNA (-34 +/- 10% and -29 +/- 5% from baseline, at 10 and 60
min respectively; P < 0.05). In sinoaortic-denervated rats, HS infusion promoted
a sustained pressor response (30 +/- 5 and 17 +/- 6 mmHg of baseline values, at
10 and 30 min respectively; P < 0.05) and abolished the increase in RVC (85 +/-
8% from baseline, at 10 min) and decrease in RSNA (-4 +/- 3% from baseline, at 10
min). These results suggest that aortic and carotid afferents are involved in
cardiovascular and renal sympathoinhibition responses induced by acute
hypernatremia.
PMID- 26440716
TI - Fifty years on.
PMID- 26440714
TI - Synthesis, cholinesterase inhibition and molecular modelling studies of coumarin
linked thiourea derivatives.
AB - Alzheimer's disease is among the most widespread neurodegenerative disorder.
Cholinesterases (ChEs) play an indispensable role in the control of cholinergic
transmission and thus the acetylcholine level in the brain is enhanced by
inhibition of ChEs. Coumarin linked thiourea derivatives were designed,
synthesized and evaluated biologically in order to determine their inhibitory
activity against acetylcholinesterases (AChE) and butyrylcholinesterases (BChE).
The synthesized derivatives of coumarin linked thiourea compounds showed
potential inhibitory activity against AChE and BChE. Among all the synthesized
compounds, 1-(2-Oxo-2H-chromene-3-carbonyl)-3-(3-chlorophenyl)thiourea (2e) was
the most potent inhibitor against AChE with an IC50 value of 0.04+/-0.01MUM,
while 1-(2-Oxo-2H-chromene-3-carbonyl)-3-(2-methoxyphenyl)thiourea (2b) showed
the most potent inhibitory activity with an IC50 value of 0.06+/-0.02MUM against
BChE. Molecular docking simulations were performed using the homology models of
both cholinesterases in order to explore the probable binding modes of
inhibitors. Results showed that the novel synthesized coumarin linked thiourea
derivatives are potential candidates to develop for potent and efficacious
acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors.
PMID- 26440717
TI - Technologies and religions.
PMID- 26440719
TI - DNA nanotechnology: Nanoscale cable tacking.
PMID- 26440720
TI - Matter-wave interference: Nanomechanical answer to Einstein.
PMID- 26440722
TI - No such thing as a bad result.
PMID- 26440723
TI - Structure and Dynamics of Solvation Shells of Copper(II) Complexes with N,O
Containing Ligands.
AB - EPR, NMR relaxation methods, and DFT calculations were jointly used to
investigate the structural and dynamical characteristics of solvation shells of
copper(II) complexes with iminodiacetic acid, glycylglycine, and
glycyglycylglycine in comparison with the copper(II) bis-glycinate studied
previously. A strong trans influence of deprotonated peptide nitrogen was
revealed in EPR spectra parameters of copper(II) complexes with oligopeptides.
With models of the experimental NMRD data and literature X-ray structural
information, it was suggested that only one water molecule coordinates in axial
position of copper(II) complexes with glycine and di- and triglycine (Cu(Gly)2,
Cu(GGH(-1)), and Cu(GGGH(-2))(-)), and the copper ion in these complexes is
pentacoordinated, while in the iminodiacetate complex, Cu(IDA), both apical
positions can be occupied by solute molecules. The obtained structural results
were confirmed by DFT calculations of structures of studied compounds using
different functionals and basis sets. It was shown that the donor ability of
equatorial ligands and trans influence have an effect on the characteristics of
the axial water bond. With increasing donor strength of equatorial ligands,
pentacoordination of copper(II) complexes in water solutions becomes more
preferable.
PMID- 26440724
TI - Fracture of the Manubrium of the Malleus.
PMID- 26440721
TI - Bridging the divide between human and environmental nanotoxicology.
AB - The need to assess the human and environmental risks of nanoscale materials has
prompted the development of new metrological tools for their detection,
quantification and characterization. Some of these methods have tremendous
potential for use in various scenarios of nanotoxicology. However, in some cases,
the limited dialogue between environmental scientists and human toxicologists has
hampered the full exploitation of these resources. Here we review recent progress
in the development of methods for nanomaterial analysis and discuss the use of
these methods in environmental and human toxicology. We highlight the
opportunities for collaboration between these two research areas.
PMID- 26440725
TI - Bilateral Vestibulopathy Documented by Video Head Impulse Tests in Superficial
Siderosis.
AB - OBJECTIVE: Superficial siderosis (SS) of the CNS is associated with cerebellar
ataxia, sensorineural hearing loss, and pyramidal symptoms, which result from
iron depositions on CNS surfaces. SS can produce bilateral vestibulopathy as the
vestibulo-cochlear nerve is particularly vulnerable. To our knowledge, however,
vestibular dysfunction in SS has not been reported thoroughly in the literature.
Here, we describe a case of bilateral vestibulopathy, documented quantitatively
by the video head impulse test (vHIT), in a patient with SS. PATIENT: A 60-year
old man presented with slowly progressing bilateral hearing loss, oscillopsia,
and a severe gait disturbance that worsened in the dark. INTERVENTION: After
noticing deficits in the bedside head impulse test in all six semicircular
canals, the patient underwent vHIT and brain MRI. MAIN OUTCOME MEASURE: MRI
demonstrated a rim of hypointensities and signal losses in T2-weighted and
gradient echo images around the cerebellum, brainstem, and vestibulo-cochlear
nerve, which were compatible with an SS diagnosis. In addition, vHIT revealed
reduced vestibule-ocular reflex (VOR) gains, and abnormal catch-up saccades (both
covert and overt saccades) in all semicircular canals. RESULTS: The vHIT showed
impaired VOR gains that were 0.55, 0.59, and 0.45 in the horizontal, anterior,
and posterior canals, respectively. CONCLUSION: SS may result in chronic
bilateral vestibulopathy with SNHL. Bilateral vestibulopathy originated
peripherally in our participant, without cerebellar dysfunctions such as those
reported in the literature. vHIT findings have not been previously reported in
patients with SS, and our study suggests that vHIT is a useful tool to document
vestibular dysfunction.
PMID- 26440726
TI - Successful Hearing Preservation After Reimplantation of a Failed Hybrid Cochlear
Implant.
AB - Objective: The purpose of this case study was to demonstrate hearing preservation
of a subject who was implanted with a 10-mm short electrode cochlear implant that
was determined to be malfunctioning at 6 months postimplantation and was
explanted and reimplanted with a 16-mm short electrode device.Study Design:
Single-subject case study.Setting: Research hospital.Patient: A 60-year old
female with a history of gradual progressive bilateral steeply sloping
sensorineural hearing loss.Intervention: Rehabilitative.Main Outcome Measure(s):
Audiometric data and speech perception in quiet and in noise were collected pre-
and postoperatively at 3 and 6 months with the 10-mm short electrode device and
pre-explantation and postoperatively at 3, 6, and 12 months with the 16-mm short
electrode device.Results: Functional hearing preservation was accomplished
following surgical implantation of both short electrode devices. Overall, the
subject had a 22 dB HL total shift in pure-tone-average (0.125-1 kHz) after two
cochlear implant surgeries. Speech perception growth was limited over the 6
months the subject was implanted with the 10-mm short electrode device. After 3
months of experience with the 16-mm short electrode device, the subject
experienced significant improvements in both speech perception in quiet and in
noise.Conclusions: The inner ear might be more robust than once thought, as was
determined through preservation of residual hearing after implantation of two
hearing preservation cochlear implants and one device explantation. Furthermore,
it is important that hearing professionals remain cognizant of unusual speech
perception patterns associated with the cochlear implant. Key Words: Hearing
preservation-Residual hearing-Short electode. [Corrected]
PMID- 26440727
TI - 5-N-Arylaminothiazoles as Highly Twisted Fluorescent Monocyclic Heterocycles:
Synthesis and Characterization.
AB - A series of 5-N-arylaminothiazoles was prepared by reacting thioamide dianions
derived from secondary thioamides with thioformamides, followed by sequential
oxidation with iodine. X-ray analyses demonstrated that they adopt structures
that are highly twisted from planar conformations. Their orientations were tuned
by the steric and/or electronic interactions of the substituents at their 2-, 4-,
and 5-positions. The 5-aminothiazoles exhibited a range of fluorescent emissions,
from blue to orange. Although the absorption spectra were independent of the
polarity of the solvent, fluorescent emissions were influenced by the polarity of
the solvent: in more polar solvents, the emissions were red-shifted. These
phenomena were examined in terms of Lippert-Mataga plots and the change in the
dipole moment between the ground and excited states. They also exhibited
emissions in the solid state, again from blue to orange. Cyclic voltammetry of
the 5-aminothiazoles showed reversible waves of one-electron oxidation. The half
potential of the oxidation was reduced by the introduction of electron-donating
groups to the phenyl groups on the nitrogen atom at the 5-position. DFT
calculations were carried out to determine the energy levels of the HOMO and
LUMO. Finally, the results of TG-DTA showed that they are thermally stable.
PMID- 26440728
TI - Validation of an early childhood caries risk assessment tool in a low-income
Hispanic population.
AB - OBJECTIVES: There is a recognized need for valid risk assessment tools for use by
both dental and nondental personnel to identify young children at risk for, or
with, precavitated stages of early childhood caries (i.e., early stage
decalcifications or white spot lesions).The aim of this study is to establish
concurrent criterion validity of "MySmileBuddy" (MSB), a novel technology
assisted ECC risk assessment and behavioral intervention tool against four
measures of ECC activity: semi-quantitative assays of salivary mutans
streptococci levels, visible quantity of dental plaque, visual evidence of enamel
decalcifications, and cavitation status (none, ECC, severe ECC). METHODS: One
hundred eight children 2-6 years of age presenting to a pediatric dental clinic
were recruited from a predominantly Spanish-speaking, low-income, urban
population. All children received a comprehensive oral examination and saliva
culture for assessment of ECC indicators. Their caregivers completed the iPad
based MSB assessment in its entirety (15-20 minutes). MSB calculated both diet
and comprehensive ECC risk scores. Associations between all variables were
determined using ordinal logistic regression. RESULTS: MSB diet risk scores were
significantly positively associated with salivary mutans (P < 0.05), and
approached significance with visible plaque levels (P < 0.1). MSB comprehensive
risk scores were significantly associated with both oral mutans and visible
plaque (P < 0.05). Neither was associated with visually evident decalcifications
or cavitations. CONCLUSIONS: Findings suggest that MSB may have clinical utility
as a valid risk assessment tool for identifying children with early precursors of
cavitations but does not add value in identifying children with extant lesions.
PMID- 26440729
TI - Antimicrobial susceptibility, virulence gene profiles and molecular subtypes of
Salmonella Newport isolated from humans and other sources.
AB - Salmonella Newport (S. Newport) is a major serotype associated with human
salmonellosis. A total of 79 S. Newport recovered from humans and other sources
in China were characterized for antimicrobial susceptibility, virulence gene
profiles and molecular subtypes using pulsed field gel electrophoresis (PFGE).
Approximately 63.3% of the isolates were susceptible to all of 16 antimicrobials
tested. Nearly one third of the isolates (31.6%) were resistant to sulfisoxazole,
20.3% to tetracycline and 13.9% to nalidixic acid. Twelve isolates (15.2%) were
resistant to three or more antimicrobials. Among 10 virulence genes detected,
Salmonella pathogenicity island genes avrA, ssaQ, mgtC, siiD, and sopB and
fimbrial gene bcfC were present in most of the isolates (93.7% to 100%). Overall,
we observed nine distinct virulence gene profiles, three of which (VP1, VP2 and
VP3) were most common (86.1%). A total of 56 PFGE patterns were identified and
mainly grouped into seven clusters (A to G) with 80% pattern similarity. Isolates
from aquatic product shared a high similarity with those from humans in several
clusters, highlighting a potential risk of aquatic product as a source of S.
Newport that infect humans. Furthermore, there was a strong association between
certain PFGE clusters and virulence gene profiles, suggesting virulence subtyping
can be a useful epidemiological tool to discriminate S. Newport isolates.
PMID- 26440730
TI - Analysis of the effects of depression associated polymorphisms on the activity of
the BICC1 promoter in amygdala neurones.
AB - The Bicaudal C Homolog 1 (BICC1) gene, which encodes an RNA binding protein, has
been identified by genome wide association studies (GWAS) as a candidate gene
associated with major depressive disorder (MDD). We explored the hypothesis that
MDD associated single-nucleotide polymorphisms (SNPs) affected the ability of cis
regulatory elements within intron 3 of the BICC1 gene to modulate the activity of
the BICC1 promoter region. We initially established that the BICC1 promoter drove
BICC1 mRNA expression in amygdala, hippocampus and hypothalamus. Intriguingly, we
provide evidence that MDD associated polymorphisms alter the ability of the BICC1
promoter to respond to PKA signalling within amygdala neurones. Considering the
known role of amygdala PKA pathways in fear learning and mood these observations
suggest a possible mechanism through which allelic changes in the regulation of
the BICC1 gene in amygdala neurones may contribute to mood disorders. Our
findings also suggest a novel direction for the identification of novel drug
targets and the design of future personalised therapeutics.The Pharmacogenomics
Journal advance online publication, 6 October 2015; doi:10.1038/tpj.2015.62.
PMID- 26440731
TI - Clinical pharmacology of tenofovir clearance: a pharmacokinetic/pharmacogenetic
study on plasma and urines.
AB - The HIV virus and hepatitis B virus nucleotide reverse transcriptase inhibitor
tenofovir has been associated with proximal tubular toxicity; the latter was
found to be predicted by plasma concentrations and with single-nucleotide
polymorphisms in transporters-encoding genes. A cross-sectional analysis in adult
HIV-positive patients with estimated creatinine clearance >60 ml min-1 was
performed. Twelve-hour plasma and urinary tenofovir concentrations and single
nucleotide polymorphisms in several transporter-encoding genes were analysed. In
289 patients 12-h tenofovir plasma, urinary and urinary to plasma ratios were 69
ng ml-1 (interquartile range 51.5-95), 24.3 mg ml-1 (14.3-37.7) and 384 (209
560). At multivariate analysis estimated creatinine clearance, protease
inhibitors co-administration and SLC28A2 CT/TT genotypes were independently
associated with plasma tenofovir exposure; ABCC10 GA/AA genotypes and protease
inhibitor co-administration were independently associated with the urinary to
plasma tenofovir ratio. Tenofovir clearance was associated with genetic
polymorphisms in host genes and with co-administered drugs: if confirmed by
ongoing studies these data may inform treatment tailoring and/or dose reductions.
PMID- 26440732
TI - A truncating mutation in Alzheimer's disease inactivates neuroligin-1 synaptic
function.
AB - Neuroligins (NLs) are cell-adhesion proteins that regulate synapse formation and
function. Neuroligin 1 (NL1) promotes the formation of glutamatergic synapses and
mediates long-term potentiation in mouse models. Thus, altered NL1 function could
mediate the synaptic and memory deficits associated with Alzheimer's disease
(AD). Here, we describe a frameshift mutation, c.875_876insTT, in the neuroligin
1 gene (NLGN1) in a patient with AD and familial history of AD. The insertion
generates a premature stop codon in the extracellular domain of NL1 (p.Thr271fs).
Expression of mutant NL1 shows accumulation of truncated NL1 proteins in the
endoplasmic reticulum. In hippocampal neurons, the p.Thr271fs mutation abolishes
the ability of NL1 to promote the formation of glutamatergic synapses. Our data
support a role for inactivating mutations in NLGN1 in AD. Previous studies have
reported rare mutations in X-linked NLGNL3 and NLGNL4 genes in patients with
autism, which result in the inactivation of the mutant alleles. Therefore,
together with a role in neurodevelopmental disorders, altered NL function could
underlie the molecular mechanisms associated with brain diseases in the elderly.
PMID- 26440733
TI - Altered transcription of inflammation-related genes in dental pulp of coeliac
children.
AB - BACKGROUND: Coeliac disease is a chronic small intestinal immune-mediated
enteropathy precipitated by exposure to dietary gluten, and possible
relationships between coeliac disease and dental pathogenic conditions during
childhood have been poorly investigated. AIM: The dental pulp plays a pivotal
role in the immune defence against possible entry of pathogens from teeth, and
the aim of this work was to investigate quantitative transcription levels of
selected genes (IL-9, IL-11, IL-15, IL-18, IL-21, IL-27, MICA, IFN-gamma) coding
for pro-inflammatory immune innate activities in the pulp of primary teeth from
healthy children and children with coeliac disease. DESIGN: The pulp from primary
teeth of 10 healthy children and 10 children with coeliac disease was used to
extract RNA and prepare cDNA for quantitative PCR transcription analysis
employing commercial nucleotide probes for selected genes. RESULTS: In children
with coeliac disease, the genes coding for pro-inflammatory cytokines IFN-gamma,
IL-11, IL-18, and IL-21 were significantly overexpressed, suggesting the possible
importance of these cytokines in the relationships between coeliac disease and
dental disorders. CONCLUSION: For the first time, we reported in dental pulp of
children possible relationships between coeliac disease and modulation in
transcription of cytokine-dependent inflammatory activities.
PMID- 26440734
TI - Mucoadhesion and mucosa-mimetic materials--A mini-review.
AB - Mucoadhesion describes an attractive interaction between dosage form and mucosal
membrane. The evaluation of mucoadhesive excipients often requires the use of ex
vivo mucosal tissues taken from laboratory animals. These can be difficult to
source, highly heterogeneous, and require the use of animal products. Thus, from
both a user-convenience and ethical point-of-view, it is desirable to produce a
synthetic alternative to these tissues-a mucosa-mimetic material. In this mini
review, the use of alternative materials to test the performance of mucoadhesives
is reviewed and discussed. There is a surprising prevalence of the use of mucosa
mimics in the literature, which hitherto has not been compiled and compared.
PMID- 26440735
TI - Inactivation of Cronobacter sakazakii in reconstituted infant formula by
combination of thymoquinone and mild heat.
AB - AIMS: The objective of this study was to determine the combined effect of
thymoquinone (TQ) and mild heat on Cronobacter sakazakii in reconstituted infant
formula. METHODS AND RESULTS: Reconstituted infant formula samples inoculated
with a mixture of four C. sakazakii strains (approx. 6.5 log CFU ml(-1) ) were
prepared with various concentrations of TQ (0, 5, 10, 20 and 30 mmol l(-1) ) and
were heated to 45, 50 and 55 degrees C for 0, 10, 20, 30, 60 and 120 min, and the
surviving populations of C. sakazakii at each sampling time were enumerated. To
elucidate the mode of action of TQ, membrane integrity and changes in cell
morphology were examined by LIVE/DEAD((r)) BacLight(TM) bacterial viability kit
and field emission scanning electron microscope respectively. TQ at 30 mmol l(-1)
reduced the pathogen to undetectable level in between 60 and 120 min at 45
degrees C, 60 min at 50 degrees C and 10 min at 55 degrees C respectively.
CONCLUSIONS: Our results demonstrated that the combined treatments significantly
reduced (P < 0.05) the population of C. sakazakii, compared to the control.
Cronobacter sakazakii numbers were reduced much more rapidly with higher
temperatures and increased concentrations of TQ. And combined treatment
inactivated pathogen partly by causing cell membrane disruption. SIGNIFICANCE AND
IMPACT OF THE STUDY: These findings suggested that TQ, together with mild heat,
may have potential application in infant formula to control C. sakazakii before
consumption and therefore is a possible way to prevent infections associated with
C. sakazakii in infant formula.
PMID- 26440736
TI - Added sugar in the nutrition facts label: Consumer needs and scientific
uncertainty.
PMID- 26440737
TI - Binding of Janus kinase inhibitor tofacitinib with human serum albumin: multi
technique approach.
AB - In this report, we have investigated the binding affinity of tofacitinib with
human serum albumin (HSA) under simulated physiological conditions by using UV
visible spectroscopy, fluorescence quenching measurements, dynamic light
scattering (DLS), differential scanning calorimetry (DSC) and molecular docking
methods. The obtained results demonstrate that fluorescence intensity of HSA gets
quenched by tofacitinib and quenching occurs in static manner. Binding parameters
calculated from modified Stern-Volmer equation shows that the drug binds to HSA
with a binding constant in the order of 10(5). Synchronous fluorescence data
deciphered the change in the microenvironment of tryptophan residue in HSA. UV
spectroscopy and DLS measurements deciphered complex formation and reduction in
hydrodynamic radii of the protein, respectively. Further DSC results show that
tofacitinib increases the thermo stability of HSA. Hydrogen bonding and
hydrophobic interaction are the main binding forces between HSA and tofacitinib
as revealed by docking results.
PMID- 26440738
TI - Is it time for flexibility in botulinum inter-injection intervals?
AB - Based largely on old retrospective reports, the recommendation of injecting BoNT
as infrequently as possible, with the lowest possible dose, was formed. While
BoNT is inherently immunogenic, with improved production, most patients no longer
develop immune resistance and poor response to BoNT is often due to other
factors. In a randomized controlled trial (RCT) using abobotulinumtoxinA for
cervical dystonia (CD) by the German Dystonia Study Group, half of the patients
treated with 250 and 500 U, and 39% in the 1000 U group required retreatment
after 8 weeks. In a RCT comparing onabotulinumtoxinA and incobotulinumtoxinA for
CD by Benecke et al., waning of effect was noted in 70 days for both toxins.
Finally, two long-term prospective trials employing flexible intervals, with
reinjections based on patient's request, have been performed using
incobotulinumtoxinA. In the CD study, 22.5% were re-injected in <10 weeks and
24.6% between 10 and 12 weeks. In the blepharospasm study, the median injection
interval was 6-10 weeks for 23.7% and 10-12 weeks for 32.3%) While long-term
studies utilizing flexible/shortened intervals, with vigilance over
immunogenicity are needed, the majority of current evidence no longer support the
very stringent adherence to strict 90-day BoNT injection intervals.
PMID- 26440739
TI - Cyclodextrin-Modified Porous Silicon Nanoparticles for Efficient Sustained Drug
Delivery and Proliferation Inhibition of Breast Cancer Cells.
AB - Over the past decade, the potential of polymeric structures has been investigated
to overcome many limitations related to nanosized drug carriers by modulating
their toxicity, cellular interactions, stability, and drug-release kinetics. In
this study, we have developed a successful nanocomposite consisting of
undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles
(UnTHCPSi NPs) loaded with an anticancer drug, sorafenib, and surface-conjugated
with heptakis(6-amino-6-deoxy)-beta-cyclodextrin (HABCD) to show the impact of
the surface polymeric functionalization on the physical and biological properties
of the drug-loaded nanoparticles. Cytocompatibility studies showed that the
UnTHCPSi-HABCD NPs were not toxic to breast cancer cells. HABCD also enhanced the
suspensibility and both the colloidal and plasma stabilities of the UnTHCPSi NPs.
UnTHCPSi-HABCD NPs showed a significantly increased interaction with breast
cancer cells compared to bare NPs and also sustained the drug release.
Furthermore, the sorafenib-loaded UnTHCPSi-HABCD NPs efficiently inhibited cell
proliferation of the breast cancer cells.
PMID- 26440740
TI - (4+1) vs (4+2): Catalytic Intramolecular Coupling between Cyclobutanones and
Trisubstituted Allenes via C-C Activation.
AB - Herein we describe a rhodium-catalyzed (4+1) cyclization between cyclobutanones
and allenes, which provides a distinct [4.2.1]-bicyclic skeleton containing two
quaternary carbon centers. The reaction involves C-C activation of cyclobutanones
and employs allenes as a one-carbon unit. A variety of functional groups can be
tolerated, and a diverse range of polycyclic scaffolds can be accessed. Excellent
enantioselectivity can be obtained, which is enabled by a TADDOL-derived
phosphoramidite ligand. The bridged bicyclic products can be further
functionalized or derivatized though simple transformations.
PMID- 26440741
TI - Preclinical combination of TP-0903, an AXL inhibitor and B-PAC-1, a procaspase
activating compound with ibrutinib in chronic lymphocytic leukemia.
PMID- 26440742
TI - Nonunion Following Trapeziometacarpal Arthrodesis With Plate and Screw Fixation.
PMID- 26440743
TI - Terrible Triad Injuries of the Elbow.
AB - The treatment of terrible triad injuries of the elbow continues to evolve. Radial
head fixation and arthroplasty, coronoid process fixation, and repair of the
lateral collateral ligament continue to be the mainstays of treatment. In the
elbow with persistent instability after repair of these elements, application of
a static external fixation, hinged external fixation, ulnohumeral joint pinning,
or an internal hinge may be needed. In patients who undergo treatment after the
acute injury period, the coronoid may require reconstruction using radial head
autograft, iliac crest autograft, olecranon autograft, or allograft.
PMID- 26440744
TI - Pediatric Trigger Digits.
AB - Pediatric trigger thumb presents not at birth but early in childhood. Most
evidence suggests that it is caused by a developmental size mismatch between the
flexor pollicis longus tendon and its sheath. Patients generally present with the
thumb interphalangeal joint locked in flexion. Surgical reviews report near
universally excellent outcomes after open release of the A1 pulley. However,
recent reports indicate that there may be a role for nonsurgical treatment for
families that are willing to wait several years for possible spontaneous
resolution of the deformity. Triggering in digits other than the thumb in
children is generally associated with an underlying diagnosis including anatomic
abnormalities of the tendons, and metabolic, inflammatory, and infectious
etiologies. Although some have advocated nonsurgical treatment, surgery is often
necessary to address the underlying anatomic etiology. More extensive surgery
beyond simple A1 pulley release is often required, including release of the A3
pulley and resection of a slip of the flexor digitorum superficialis tendon.
PMID- 26440745
TI - Exclusion of a Huge Left Ventricular Outflow Tract Pseudoaneurysm with Konno's
Procedure.
AB - We present the use of Konno's procedure for the reconstruction of a huge left
ventricular outflow tract pseudoaneurysm formed after aortic valve replacement.
PMID- 26440746
TI - From Arabidopsis to cereal crops: Conservation of chloroplast protein degradation
by autophagy indicates its fundamental role in plant productivity.
AB - Autophagy is an evolutionarily conserved process leading to the degradation of
intracellular components in eukaryotes, which is important for nutrient recycling
especially in response to starvation conditions. Nutrient recycling is an
essential process that underpins productivity in crop plants, such that
remobilized nitrogen derived from older organs supports the formation of new
organs or grain-filling within a plant. We extended our understanding of
autophagy in a model plant, Arabidopsis thaliana, to an important cereal, rice
(Oryza sativa). Through analysis of transgenic rice plants stably expressing
fluorescent marker proteins for autophagy or chloroplast stroma, we revealed that
chloroplast proteins are partially degraded in the vacuole via Rubisco-containing
bodies (RCBs), a type of autophagosomes containing stroma. We further reported
evidence that the RCB pathway functions during natural leaf senescence to
facilitate subsequent nitrogen remobilization into newly expanding leaves. Thus,
our recent studies establish the importance of autophagy in biomass production of
cereals.
PMID- 26440747
TI - Different effects of five depigmentary compounds, rhododendrol, raspberry ketone,
monobenzone, rucinol and AP736 on melanogenesis and viability of human epidermal
melanocytes.
AB - Numerous medications are used to treat hyperpigmentation. However, several
reports have indicated that repeated application of some agents, such as
rhododendrol (RD), raspberry ketone (RK) and monobenzone (MB), can be toxic to
melanocytes. Although these agents had severe side effects in human trials, no
current in vitro methods can predict the safety of such drugs. This study
assessed the in vitro effects of five depigmentary compounds including leukoderma
inducing agents. In particular, we determined the effects of different
concentrations and exposure times of different depigmentary agents on cell
viability and melanogenesis in the presence and absence of ultraviolet B (UVB)
radiation. Concentrations of RD, RK and MB that inhibit melanogenesis are similar
to concentrations that are cytotoxic; however, concentrations of rucinol (RC) and
AP736 that inhibit melanogenesis are much lower than concentrations that are
cytotoxic. Furthermore, the concentrations that cause toxic effects depend on
exposure duration, and prolonged exposure to RD, RK and MB had more cytotoxic
effects than prolonged exposure to RC and AP736. The cytotoxic effects of RD and
RK appear to be mediated by apoptosis due to increased expression of caspase-3
and caspase-8; UVB radiation increased the cytotoxicity of these agents and also
increased caspase activity. Our results indicate that different leukoderma
inducing compounds have different effects on the viability of normal epidermal
melanocytes and suggest that the in vitro assay used here can be used to predict
whether an investigational compound that induces leukoderma may lead to adverse
effects in human trials.
PMID- 26440748
TI - Symmetry analysis for monitoring safety of newly marketed drugs.
AB - INTRODUCTION: A postmarketing study without a comparator group has been
recognized as a problem as it provides no measure of association. Nevertheless,
the design is sometimes used in company postmarketing studies particularly when
the study involves the primary data collection. In this report, the "Symmetry
Analysis Cohort Design" without a comparator group but with a control period is
proposed. METHODS AND RESULTS: In the proposed design, the rate ratio is
estimated using the method of prescription sequence symmetry analysis with slight
modification so that the rate ratio can be estimated using data on subjects who
have started the drug during the study period but no data on other subjects.
DISCUSSION: The proposed design has an advantage that it can provide the measure
of association. Another advantage common to all self-controlled methods is that
the effect of the measured and unmeasured confounders is automatically canceled
out when the effect is stable over the study period. Compared with the standard
design with a comparator group, the proposed design also has weaknesses. For
example, adjustment of confounding by the indication may be difficult when the
indication is an acute condition. In addition, the rate ratio is not valid when
the probability of the prescription of the drug is dependent on the occurrence of
the outcome in the unexposed (pre-dose) period. The design may be used to
evaluate the need for further studies although its real usefulness is to be
determined in the future.
PMID- 26440749
TI - Lenalidomide Treatment for Lower Risk Nondeletion 5q Myelodysplastic Syndromes
Patients Yields Higher Response Rates When Used Before Azacitidine.
AB - BACKGROUND: Lenalidomide and azanucleosides are commonly used to treat anemic
patients with lower-risk myelodysplastic syndromes (LR-MDS) without chromosome 5q
deletion (non-del5q) after failure of treatment with erythropoiesis-stimulating
agents (ESAs). Nonetheless, response rates to lenalidomide after azanucleosides
treatment failure and their optimal sequencing after failure of treatment with
ESAs is unknown. PATIENTS AND METHODS: We identified patients with LR-MDS in the
Moffitt Cancer Center Clinical Database who received lenalidomide and azacitidine
after ESA treatment failure. Rates of erythroid hematologic improvement (HI-E) in
patients who received lenalidomide first followed by azacitidine (group 1) and
those who received lenalidomide after azacitidine (group 2) were examined
according to the International Working Group 2006 criteria. RESULTS: Sixty-three
patients (37 in group 1 and 26 in group 2) were identified. The HI-E rate with
lenalidomide as first-line therapy was 38% versus only 12% when lenalidomide was
used as second-line therapy (P = .04). There were no significant differences in
overall survival (OS; median OS, 104 vs. 87 months, respectively; P = .55), rates
of leukemic progression, or in HI-E rates after azacitidine use (38% when
azacitidine was used after lenalidomide vs. 35% when azacitidine was administered
before lenalidomide, P = .69). CONCLUSION: Lenalidomide appears to yield a higher
HI-E rate in non-del5q LR-MDS when used as first-line therapy after ESA
treatments failure. If validated in larger cohorts, lenalidomide rather than
azacitidine should be considered for first-line therapy after ESA treatment
failure.
PMID- 26440750
TI - Subtle Dynamic Changes Accompany Hck Activation by HIV-1 Nef and are Reversed by
an Antiretroviral Kinase Inhibitor.
AB - The HIV-1 virulence factor Nef interacts with the macrophage Src-family kinase
Hck, resulting in constitutive kinase activation that contributes to viral
replication and immune escape. Previous chemical library screens identified the
diphenylfuranopyrimdine kinase inhibitor DFP-4AB, which selectively inhibits Nef
dependent Hck activity in biochemical assays and potently blocks HIV replication
in vitro. In the present study, hydrogen exchange mass spectrometry (HX MS) was
used to study conformational changes in downregulated Hck that result from Nef
binding, as well as the impact of DFP-4AB on these changes. Remarkably,
interaction with Nef induced only subtle changes in deuterium uptake by Hck, with
the most significant changes in the N-lobe of the kinase domain adjacent to the
docking site for Nef on the SH3 domain. No changes in hydrogen exchange were
observed in the Hck SH2 domain or C-terminal tail, indicating that this
regulatory interaction is unaffected by Nef binding. When HX MS was performed in
the presence of DFP-4AB, the effect of Nef on Hck N-lobe dynamics was completely
reversed. These results show that constitutive activation of Hck by HIV-1 Nef
requires only modest changes to the conformational dynamics of the overall kinase
structure. DFP-4AB reverses these effects, consistent with its activity against
this Nef-induced signaling event in HIV-infected cells.
PMID- 26440752
TI - PROTEOMICS ANALYSIS OF OVEREXPRESSED PLASMA PROTEINS IN RESPONSE TO COLD
ACCLIMATION IN Ostrinia furnacalis.
AB - Many insects in temperate regions overwinter in diapause. In these insects, one
of the metabolic adaptations to cold stress is the synthesis of responsive
proteins. Using proteomic analysis, an investigation aimed to a better
understanding of the molecular adaptation mechanisms to cold stress was carried
out in Ostrinia furnacalis larva. Proteins were extracted from the larval
hemolymph collected from both control and overwintering larva. By polyethylene
glycol precipitation, approximately 560 protein spots were separated and
visualized on two-dimensional (2D) gels after silver staining. Eighteen protein
spots were found to be upregulated in overwinter larval plasma in different
patterns. As an initial work, 13 of these proteins were identified using MALDI
TOF/TOF MS. The differentially overexpressed proteins include heat shock 70 kDa
cognate protein, small heat shock protein (sHSP), putative aliphatic nitrilase,
arginine kinase, phosphoglyceromutase, triosephosphateisomerase, and glutathione
transferase. Alterations in the levels of these proteins were further confirmed
by qPCR. This study is the first analysis of differentially expressed plasma
proteins in O. furnacalis diapause larvae under extremely low temperature
conditions and gives new insights into the acclimation mechanisms responsive to
cold stress. Our results also support the idea that energy metabolism, alanine
and proline metabolism, and antioxidative reaction act in the cold acclimation of
O. furnacalis diapause larvae.
PMID- 26440751
TI - Rhodium-Catalyzed Stereoselective Intramolecular [5 + 2] Cycloaddition of 3
Acyloxy 1,4-Enyne and Alkene.
AB - The first rhodium-catalyzed intramolecular [5 + 2] cycloaddition of 3-acyloxy 1,4
enyne and alkene was developed. The cycloaddition is highly diastereoselective in
most cases. Various cis-fused bicyclo[5.3.0]decadienes were prepared
stereoselectively. The chirality in the propargylic ester starting materials
could be transferred to the bicyclic products with high efficiency. Electron
deficient phosphine ligand greatly facilitated the cycloaddition. Up to three new
stereogenic centers could be generated. The resulting diene in the products could
be hydrolyzed to enones, which allowed the introduction of more functional groups
to the seven-membered ring.
PMID- 26440753
TI - INCIDENCE OF, AND RISK FACTORS FOR, MALNUTRITION AMONG CHILDREN AGED 5-7 YEARS IN
SOUTH INDIA.
AB - Protein-energy malnutrition is a major health problem contributing to the burden
of disease in developing countries. The aim of this study was to assess the
incidence of, and risk factors for, malnutrition among school-going children in
south India. A total of 2496 children aged 5-7 years from rural and urban areas
of south India were recruited in 1982 and followed up for malnutrition over a
period of 9 years. Their body heights and weights were measured every six months
and socio-demographic factors such as mother's education and father's education
and relevant household characteristics and hygiene practices collected. Body mass
index and height-for-age z-scores were used to determine children's levels of
underweight and stunting, respectively, classified as normal, mild/moderate or
severe. Risk factor analysis was done for pre-pubertal ages only using
Generalized Estimating Equations with cumulative odds assumption. There was a
significant difference between male and female children in the incidence of
severe underweight and stunting (6.4% and 4.2% respectively). Children in
households with no separate kitchen had 1.3 (1.0-1.6) times higher odds of being
severely underweight (p=0.044) compared with those with a kitchen. Children
without a toilet facility had significantly higher odds of severe underweight
compared with those who did. Children with illiterate parents had higher odds of
severe stunting than those with literate parents. In conclusion, the prevalence
of malnutrition among these south Indian children has not changed over the years,
and the incidence of severe malnutrition was highest in children when they were
at pubertal age. The risk factors for stunting were mostly poverty-related, and
those for underweight were mostly hygiene-related. Adolescent children in south
India should be screened periodically at school for malnutrition and provided
with nutritional intervention if necessary.
PMID- 26440754
TI - Is Action Planning Helpful for Smoking Cessation? Assessing the Effects of Action
Planning in a Web-Based Computer-Tailored Intervention.
AB - BACKGROUND AND OBJECTIVES: The aim of this study was to examine the efficacy of a
web-assisted computer-tailored smoking cessation intervention, an action planning
(AP) intervention in which potential quitters were encouraged to form action
plans (e.g., plan a quit date) and execute them (e.g., remove ashtrays). We also
investigated whether the AP intervention resulted in more AP and plan execution
than a similar, control intervention without the supplementary AP component.
METHODS: In a randomized controlled trial, the AP intervention (N = 977) was
compared with the control intervention (N = 1,005) in terms of self-reported
continued abstinence (CA) and point prevalence abstinence (PPA) six months after
baseline. AP, plan execution, and opinion of the intervention were measured one
month after baseline. RESULTS: Complete-case logistic regression analysis showed
that the AP intervention had a significant effect on CA (OR = 2.01; CI 1.08-3.84,
p = .02), whereas intention-to-treat analysis showed a borderline significant
effect (OR = 1.68; CI .96-2.92, p = .07). Sixteen percent of the experimental
group achieved CA compared to 10% of the control group. The AP intervention had
no effect on PPA. The experimental group also showed significantly more AP and
plan execution at one month. Execution of plans was associated with smoking
cessation. CONCLUSIONS: The effects of the AP intervention on CA, AP, and
execution of plans were encouraging. The potential for widespread use of web
based interventions means that even small behavioral effects may have an impact
on public health. We recommend that the intervention be intensified and improved.
PMID- 26440755
TI - Epidemiology of tinea capitis in northeast Iran: a retrospective analysis from
1998 to 2012.
AB - BACKGROUND: Tinea capitis is a common disease of the pediatric population. This
disease typically follows one of several clinical patterns, i.e., scaling, hair
loss, and/or inflammatory lesions, which are usually caused predominantly by two
dermatophytic genera: Microsporum and Trichophyton. The aim of this study was to
investigate tinea capitis and its etiological agents in Sari city of Mazandaran
province, Iran. METHODS: We studied the spectrum of tinea capitis by means of a
retrospective analysis involving 1745 patients referred to both the Reference
Laboratory of Medical Mycology (RLMM) and Bo Ali Sina Hospital at Sari, Iran
(1998-2012). Specimens were assessed by standard mycological techniques based on
macroscopic and microscopic morphology. RESULTS: Among the patients, 480 (27.5%;
61 males and 39% females) were confirmed through a mycological examination. The
peak incidence was in the 5-14 years age group. Endothrix (263 cases; 54.8%) was
the most frequent clinical feature by direct exam. The predominant causative
agents of tinea capitis were T. tonsurans (186 cases; 38.8%) and T. violaceum
(119 cases; 24.8%), followed by T. mentagrophytes (46 cases; 9.6%), T.
schoenleinii (28; 5.8%), T. rubrum (20 cases; 4.2%), M. gypseum (15 cases; 3.1%),
T. verrucosum (14 cases; 2.9%), and Epidermophyton floccosum (1 cases; 0.2%).
CONCLUSION: The present study showed that tinea capitis is mainly due to the
anthropophilic species, and the most common species were T. tonsurans and T.
violaceum. Owing to the high frequency of anthropophilic species, future studies
may be useful in the development of preventive and educational strategies to
reduce healthcare expenditure.
PMID- 26440756
TI - Free DOX and chitosan-N-arginine conjugate stabilized indocyanine green
nanoparticles for combined chemophotothermal therapy.
AB - Indocyanine green (ICG) is a FDA-approved near-infrared (NIR) cyanine dye used in
medical diagnostics. However, the utility of ICG remains limited by its unstable
optical property, and concentration-dependent aggregation and precipitation. A
chitosan-arginine conjugate (CS-N-Arg) was developed to increase the stability of
ICG in physiological buffer saline via formation of strong electrostatic
interactions between ICG and CS-N-Arg. The CS-N-Arg/ICG complex prevented ICG
from aggregation and precipitation, thus it could serve as a theranostic
nanomaterial for image-guided photothermal cancer therapy. The CS-N-Arg/ICG NPs
showed excellent photostability, clear fluorescent images, and rapid temperature
rise under laser irradiation. Cell viability assay indicated that CS-N-Arg/ICG
NPs could efficiently suppress the growth of doxorubicin (DOX) resistant breast
cancer cell (MCF-7/ADR cells) under NIR photothermal treatments. In combination
of DOX with CS-N-Arg/ICG NPs, a combined effect was observed in MCF-7/ADR breast
cancer cells due to dual hyperthermia and chemical therapeutic effects. The
present observations suggest that CS-N-Arg/ICG NPs can effectively deliver ICG
molecules to MCF-7/ADR breast cancer cells and overcome DOX resistance in the
cells by hyperthermia.
PMID- 26440757
TI - Hyaluronic acid-conjugated polyamidoamine dendrimers for targeted delivery of 3,4
difluorobenzylidene curcumin to CD44 overexpressing pancreatic cancer cells.
AB - The current study was aimed to develop a targeted dendrimer formulation of 3, 4
difluorobenzylidene curcumin (CDF) and evaluate its potential in CD44 targeted
therapy for pancreatic cancer. Using amine terminated fourth generation
poly(amidoamine) (PAMAM) dendrimer nanocarrier and hyaluronic acid (HA) as a
targeting ligand, we engineered a CD44-targeted PAMAM dendrimer (HA-PAMAM)
formulation of CDF. The resulting dendrimer nanosystem (HA-PAMAM-CDF) had a
particle size and surface charge of 9.3 +/- 1.5 nm and -7.02 +/- 9.53 mV,
respectively. When CD44 receptor overexpressing MiaPaCa-2 and AsPC-1 human
pancreatic cancer cells were treated with HA-PAMAM-CDF, a dose-dependent
cytotoxicity was observed. Furthermore, blocking the CD44 receptors present on
the MiaPaCa-2 cells using free excess soluble HA prior to treatment with HA-PAMAM
CDF nano-formulation resulted in 1.71 fold increase in the IC50 value compared to
non-targeted formulation (PAMAM-CDF), confirming target specificity of HA-PAMAM
CDF. Additionally, HA-PAMAM-CDF formulation when compared to PAMAM-CDF, displayed
higher cellular uptake in MiaPaCa-2 cancer cell lines as shown by fluorescence
studies. In summary, the novel CD44 targeted dendrimer based nanocarriers appear
to be proficient in mediating site-specific delivery of CDF via CD44 receptors,
with an improved therapeutic margin and safety.
PMID- 26440758
TI - Immobilization of enzymes using non-ionic colloidal liquid aphrons (CLAs):
Surface and enzyme effects.
AB - The use of non-ionic colloidal liquid aphrons (CLAs) as a support for enzyme
immobilisation was investigated. Formulation required the mixing of an aqueous
surfactant solution with a relatively non-polar solvent-surfactant solution,
forming a solvent droplet surrounded by a thin stabilised aqueous film (soapy
shell). Studies utilising anionic surfactants have showed increased retention,
however, very little have been understood about the forces governing
immobilisation. This study seeks to determine the effects of enzyme properties on
CLA immobilisation by examining a non-ionic/non-polar solvent system comprised of
two non-ionic surfactants, Tween 20 and 80, mineral oil and the enzymes lipase,
aprotinin and alpha-chymotrypsin. From these results it was deduced that
hydrophobic interactions strongly governed immobilisation. Confocal Scanning
Laser Microscopy (CSLM) revealed that immobilisation was predominantly achieved
by surface adsorption attributed to hydrophobic interactions between the enzyme
and the CLA surface. Enzyme surface affinity was found to increase when added
directly to the formulation (pre-manufacture addition), as opposed to the bulk
continuous phase (post-manufacture addition), with alpha-chymotrypsin and
aprotinin being the most perturbed, while lipase was relatively unaffected. The
effect of zeta potential on immobilisation showed that enzymes adsorbed better
closer to their pI, indicating that charge minimisation was necessary for
immobilisation. Finally, the effect of increasing enzyme concentration in the
aqueous phase resulted in an increase in adsorption for all enzymes due to
cooperativity between protein molecules, with saturation occurring faster at
higher adsorption rates.
PMID- 26440759
TI - Effect of temperature on extracellular organic matter (EOM) of Chlorella
pyrenoidosa and effect of EOM on irreversible membrane fouling.
AB - Extracellular organic matter (EOM) can cause serious membrane fouling during the
algae harvesting process. In this study, the secretion of EOM, including bound
EOM (bEOM) and dissolved-EOM (dEOM), by Chlorella pyrenoidosa (C. pyrenoidosa) at
different culturing temperatures, and their influences on membrane filtration,
have been investigated. The secretion of EOM was markedly reduced at high
temperatures. The specific EOM secretion rate (SEOM) reached 831.1 +/- 55.3mg/g
at the lowest temperatures of 15 degrees C; in contrast, the SEOM decreased to
only 370-442 and 356-406 mg/g with temperature rising above 20-25 and 30-35
degrees C, respectively. Based on membrane filtration experiments, the influence
of EOM on irreversible membrane fouling was studied. In a critical flux
experiment, low critical flux (24 L/m(2)h) was observed in a system with a high
EOM concentration. The fouled membranes were rinsed by water and then used for
continuous filtration, scanning electron microscope (SEM) analysis and fourier
transform infrared spectroscopy (FTIR) analysis. The results revealed that there
was irreversible membrane fouling caused by EOM, and irreversible membrane
fouling can be more serious when an algae solution contains high EOM levels.
PMID- 26440761
TI - Non-alignment stagnation-point flow of a nanofluid past a permeable
stretching/shrinking sheet: Buongiorno's model.
AB - The paper deals with a stagnation-point boundary layer flow towards a permeable
stretching/shrinking sheet in a nanofluid where the flow and the sheet are not
aligned. We used the Buongiorno model that is based on the Brownian diffusion and
thermophoresis to describe the nanofluid in this problem. The main purpose of the
present paper is to examine whether the non-alignment function has the effect on
the problem considered when the fluid suction and injection are imposed. It is
interesting to note that the non-alignment function can ruin the symmetry of the
flows and prominent in the shrinking sheet. The fluid suction will reduce the
impact of the non-alignment function of the stagnation flow and the
stretching/shrinking sheet but at the same time increasing the velocity profiles
and the shear stress at the surface. Furthermore, the effects of the pertinent
parameters such as the Brownian motion, thermophoresis, Lewis number and the
suction/injection on the flow and heat transfer characteristics are also taken
into consideration. The numerical results are shown in the tables and the
figures. It is worth mentioning that dual solutions are found to exist for the
shrinking sheet.
PMID- 26440760
TI - Augmented microscopy: real-time overlay of bright-field and near-infrared
fluorescence images.
AB - Intraoperative applications of near-infrared (NIR) fluorescent contrast agents
can be aided by instrumentation capable of merging the view of surgical field
with that of NIR fluorescence. We demonstrate augmented microscopy, an
intraoperative imaging technique in which bright-field (real) and electronically
processed NIR fluorescence (synthetic) images are merged within the optical path
of a stereomicroscope. Under luminance of 100,000 lx, representing typical
illumination of the surgical field, the augmented microscope detects 189 nM
concentration of indocyanine green and produces a composite of the real and
synthetic images within the eyepiece of the microscope at 20 fps. Augmentation
described here can be implemented as an add-on module to visualize NIR contrast
agents, laser beams, or various types of electronic data within the surgical
microscopes commonly used in neurosurgical, cerebrovascular, otolaryngological,
and ophthalmic procedures.
PMID- 26440762
TI - Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular
Hemorrhage.
AB - We recently showed that intraventricular transplantation of human umbilical cord
blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuated
posthemorrhagic hydrocephalus (PHH) and brain injury after severe
intraventricular hemorrhage (IVH) in newborn rat pups. The purpose of this study
was to optimize the timing of MSC transplantation for severe IVH. Severe IVH was
induced by injecting 100 ul of blood into each ventricle of Sprague-Dawley rats
on postnatal day 4 (P4). Human UCB-derived MSCs (1 * 10(5) cells in 10 ul of
normal saline) were transplanted intraventricularly under stereotaxic guidance
either early at P6 or late at P11. Serial brain MRIs and behavioral function
tests, such as negative geotaxis and rotarod tests, were performed. At P32, brain
tissue samples were obtained for histological and biochemical analyses.
Intracerebroventricular transplantation of MSCs significantly attenuated the
development of PHH, behavioral impairment, increased apoptosis and astrogliosis,
reduced corpus callosum thickness and brain myelination, and upregulated
inflammatory cytokines including interleukin (IL)-1alpha, IL-1beta, IL-6, and
tumor necrosis factor-alpha (TNF-alpha) at P6 but not at P11 after induction of
severe IVH. Intracerebroventricular transplantation of human UCB-derived MSCs
attenuated PHH and brain injury after severe IVH in newborn rats in a time
dependent manner. Significant neuroprotection was only demonstrated when
administered early at 2 days after induction but not late at 7 days after
induction of severe IVH.
PMID- 26440763
TI - An anatomical study of the dorsal and ventral nasal conchal bullae in normal
horses: Computed tomographic anatomical and morphometric findings.
AB - REASONS FOR PERFORMING STUDY: Infection of the dorsal nasal conchal bulla and
ventral nasal conchal bulla has recently been shown to cause clinical disease in
horses, but the anatomy of these 2 structures is poorly documented. OBJECTIVES:
To describe the anatomical features, dimensions and relationships to adjacent
structures of the dorsal conchal bulla and ventra conchal bulla in normal horses
using computed tomography (CT). STUDY DESIGN: Descriptive imaging study using
cadavers. METHODS: Computed tomographic images acquired from 60 equine cadaver
heads that were shown to be free of sinonasal disease were categorised into 3 age
groups (0-5; 6-15; >16 years old). Linear and volumetric measurements and
descriptive anatomical assessments of the dorsal conchal bulla and ventral
conchal bulla were produced from these CT images and the anatomical relationships
between the dorsal conchal bulla and ventral conchal bulla and the adjacent
structures, particularly the maxillary cheek teeth, were examined. The
associations between bullae dimensions with horse ages and skull dimensions were
assessed using linear regression. RESULTS: Mean (range) dorsal conchal bulla
measurements were: length 7.5 cm (4.6-14), width 1.9 cm (1.3-2.5), height 2.8 cm
(1.8-4), volume 24 cm3 (5.9-50.5). Mean ventral conchal bulla measurements were:
length 5.7 cm (2.5-8.5), width 1.6 cm (0.7-2.9), height 2.4 cm (0.8-3.7), volume
15 cm3 (0.4-30). In both dorsal conchal bulla and ventral conchal bulla, there
were significant differences in sizes between the different age groups (smaller
in younger animals). In the ventral conchal bulla, this was probably related to
protrusion of the large dental alveoli of younger horses into the lateral nasal
cavity. Measures of bullae size and volume were significantly associated with
head size. The anatomical positions (rostro-caudal boundaries) of the dorsal
conchal bulla and ventral conchal bulla were closely associated with specific
maxillary cheek teeth. CONCLUSIONS: Computed tomography was a useful technique to
establish the linear and volumetric dimensions of the nasal conchal bullae in
normal horses. Both dorsal conchal bulla and ventral conchal bulla sizes
increased with animal age. Relatively consistent anatomical relationships were
shown between the rostral and caudal limits of the bullae and certain maxillary
cheek teeth, which would be of diagnostic value with conventional radiography and
act as landmarks in the surgical treatment of nasal bulla disease.
PMID- 26440764
TI - Dermochondrocorneal dystrophy (Francois syndrome) in a Mexican patient and
literature review.
AB - Dermochondrocorneal Dystrophy (OMIM 221800) is a very rare disease first
described by Francois in 1949. It is characterized by the appearance of skin
nodules, osteochondral deformities, and corneal opacities during childhood. Only
a few cases have been reported. There is uncertainty about the inheritance
pattern and no gene or genes have been associated to this disease. We report a
patient from Mexican mestizo origin with the classic manifestations of
Dermochondrocorneal Dystrophy. We perform a multidisciplinary assessment in order
to contribute to the knowledge of the clinical presentation of this uncommon
condition. Among the few documented patients, this is the third patient of
Mexican ancestry reported with this syndrome.
PMID- 26440765
TI - One-pot synthesis of benzoxaborole derivatives from the palladium-catalyzed cross
coupling reaction of alkoxydiboron with unprotected o-bromobenzylalcohols.
AB - Under very mild conditions, functionalized benzoxaborole derivatives were
prepared in good to excellent yields via a palladium-catalyzed Miyaura borylation
reaction of readily available unprotected o-bromobenzylalcohols, and
bis(pinacolato)diboron (B2pin2) without the assistance of an acid. Blue-light
emitting materials based on spiro benzoxaborole building blocks have been
obtained with potential applications in organic electronics and biomedicine.
PMID- 26440766
TI - Editorial Comment on "Adjuvant Maneuvers for Residual Curvature Correction during
Penile Prosthesis Implantation in Men with Peyronie's Disease".
PMID- 26440767
TI - Mid-term clinical outcomes of ABSORB bioresorbable vascular scaffold implantation
in a real-world population: A single-center experience.
AB - BACKGROUND: Available data on the use of the ABSORB bioresorbable vascular
scaffold (BVS) (Abbott Vascular, Santa Clara, CA) in real-world patients is
limited. The aim of this study was to assess the mid-term clinical outcomes in a
real-world population treated with ABSORB BVS. METHODS AND MATERIALS: We
retrospectively evaluated all patients treated with ABSORB at Papworth Hospital,
Papworth Everard, UK between July 2012 and July 2014. A total of 108 patients
(126 lesions) were identified. Clinical follow-up was performed on all subjects
by clinic visit or telephone interview. RESULTS: Most patients were male (91.7%)
with a relative high incidence of previous myocardial infarction (MI) (40.7%).
Clinical presentation was equally divided between stable angina and acute
coronary syndrome (ACS) (51.8% vs. 48.2%, p=0.59). Of the ACS patients, 26.9%
presented with ST-elevation myocardial MI. Intravascular imaging was used in all
cases. Predilatation (92.9%) and postdilatation (82.5%) were frequently
performed. Major adverse cardiac event (MACE) rates defined as the composite of
all-cause death, follow-up MI and target vessel revascularization were 2.5% at 6
month and 4.5% at 1-year. The 1-year target lesion failure rate, defined as the
composite of cardiac death, target-vessel MI and target lesion revascularization
was 1.9%. There was 1 case of subacute stent thrombosis. CONCLUSIONS: The use of
ABSORB BVS in real-world patients appears to be associated with good mid-term
clinical outcomes when guided by intravascular imaging. Larger studies are
required to evaluate further the role of BVS in routine clinical practice and
examine how this compares to metallic devices. SUMMARY: Available data on the use
of the ABSORB BVS in real-world patients is limited. We retrospectively evaluated
all patients treated with ABSORB BVS between July 2012 and July 2014. A total of
108 patients (126 lesions) were identified. Clinical presentation was equally
divided between stable angina and acute coronary syndrome (51.8% vs. 48.2%,
p=0.59). Predilatation (92.9%) and postdilatation (82.5%) were frequently
performed. Estimated MACE rates at 6-month and 1-year were 2.5% and 4.5%
respectively, with a 1-year TLF rate of 1.9%. These results suggest that the use
of ABSORB BVS use in the real-world is associated with good mid-term clinical
outcomes when guided by intravascular imaging.
PMID- 26440768
TI - Cost-effectiveness of transcatheter versus surgical management of structural
heart disease.
AB - Transcatheter management of valvular and structural heart disease is the most
growing aspect of interventional cardiology. While the early experience was
limited to patients who were not candidate for surgery, the continuous
improvement in the efficacy and safety expanded its use to different degree
depending on the procedure and the disease involved. The cost of these procedures
is a major concern for health care in developed world. Cost-effectiveness of
these transcatheter structural procedures varies depending on the procedure
itself, the burden of the underlying disease, the feasibility and cost of both
the Transcatheter and surgical procedures. In this review, we turn now to a
specific discussion of the medical economics of percutaneous valvular and
structural interventions.
PMID- 26440770
TI - Tuning the Ising-type anisotropy in trigonal bipyramidal Co(II) complexes.
AB - This paper demonstrates the engineering and tuning of Ising-type magnetic
anisotropy in trigonal bipyramidal Co(II) complexes. Here, we predict that
employing a ligand that forces a trigonal bipyramidal arrangement and has weak
equatorial sigma-donating atoms, increases (in absolute value) the negative zero
field splitting parameter D. With these considerations in mind, we used a sulfur
containing ligand (NS3(iPr)), which imposes a trigonal bipyramidal geometry to
the central Co(II) ion with long equatorial Co-S bonds. The resulting complex
exhibits a larger anisotropy barrier and a longer relaxation time in comparison
to the complex prepared with a nitrogen containing ligand (Me6tren).
PMID- 26440769
TI - The C-terminal amyloidogenic peptide contributes to self-assembly of
Avibirnavirus viral protease.
AB - Unlike other viral protease, Avibirnavirus infectious bursal disease virus (IBDV)
encoded viral protease VP4 forms unusual intracellular tubule-like structures
during viral infection. However, the formation mechanism and potential biological
functions of intracellular VP4 tubules remain largely elusive. Here, we show that
VP4 can assemble into tubules in diverse IBDV-infected cells. Dynamic analysis
show that VP4 initiates the assembly at early stage of IBDV infection, and
gradually assembles into larger size of fibrils within the cytoplasm and nucleus.
Intracellular assembly of VP4 doesn't involve the host cytoskeleton, other IBDV
encoded viral proteins or vital subcellular organelles. Interestingly, the last C
terminal hydrophobic and amyloidogenic stretch (238)YHLAMA(243) with two
"aggregation-prone" alanine residues was found to be essential for its
intracellular self-assembly. The assembled VP4 fibrils show significantly low
solubility, subsequently, the deposition of highly assembled VP4 structures
ultimately deformed the host cytoskeleton and nucleus, which was potentially
associated with IBDV lytic infection. Importantly, the assembly of VP4
significantly reduced the cytotoxicity of protease activity in host cells which
potentially prevent the premature cell death and facilitate viral replication.
This study provides novel insights into the formation mechanism and biological
functions of the Avibirnavirus protease-related fibrils.
PMID- 26440771
TI - Bosma arrhinia microphthalmia syndrome in a Mexican patient with a molecular
analysis of PAX6.
AB - The association of anophthalmia, arrhinia, and hypogonadism constitutes the major
clinical features for Bosma arrhinia microphthalmia syndrome. However, there is
variability in the presentation of this disease; arrhinia is the most constant
clinical feature, which is then combined with a spectrum of
anophthalmia/microphthalmia and/or hypogonadism. This rare entity is not
associated with any specific genes, but the genes that are related to arrhinia
and anophthalmia have been studied in an attempt to explain this phenomenon. We
analyzed the PAX6 gene in a Bosma arrhinia microphthalmia syndrome patient but
found no variation or mutation that could constitute or establish a causal
association in our patient.
PMID- 26440772
TI - Optimal blood pressure in patients with peripheral artery disease following
endovascular therapy.
AB - This study examined the associations between blood pressure (BP) and event
incidence to define optimal BP after endovascular therapy (EVT) in patients who
underwent EVT. BP was monitored every 6 months for 5 years, and the patients were
divided into two groups by average BP: >= 140/90 mmHg and < 140/90 mmHg. The
association of BP with several events was examined. Although no significant
differences in total mortality were observed between the groups, restenosis rates
were significantly higher among patients who did not achieve target BP (36.2%)
than among those who did (18.2%) (p < 0.01). The percentage of patients with
glycosylated haemoglobin > 7.0% was significantly higher among those who did not
achieve target BP in the restenosis group (42.9%) than in the other group (10.8%)
(p < 0.01). In the restenosis group, there was a significantly higher percentage
of patients taking metformin (p < 0.01) than in the other group. Metformin seemed
to be administered to patients with more severe diabetes mellitus. In conclusion,
it is important to manage hypertension and diabetes to prevent restenosis after
EVT.
PMID- 26440773
TI - Learning to drink: How Chinese adolescents make decisions about the consumption
(or not) of alcohol.
AB - BACKGROUND: The aim of the study was to provide in-depth understanding of how
Chinese adolescents learn to drink and how they make decisions about the
consumption (or not) of alcohol. This study explored the ways in which social and
cultural factors shape the drinking trajectories of Chinese underage young
people. METHODS: The study used a qualitative design to collect and analyse the
data. We recruited adolescents aged between 14 and 17 from a range of secondary
schools in Hong Kong. Focus group interviews were undertaken with 22 groups
encompassing 111 participants. A thematic analysis based upon grounded theory was
performed using NVivo 10. RESULTS: The traditional Chinese drinking culture,
characterised by the coming together of friends and relatives for celebrations,
signifies the Chinese adolescents' first alcohol experiment. The adolescents'
motivations for drinking essentially reflect the value placed upon alcohol within
the Chinese culture - promoting conviviality, sociability and camaraderie.
Whereas a sense of commonality encouraged alcohol use among them, there was
little indication that drinkers and non-drinkers separately clustered around
friendship networks. A high degree of self-regulation was exercised when drinking
and this emerged as an acceptable social norm amongst young drinkers within
social and cultural contexts. Most respondents saw underage drinking as an
entirely normal and accepted part of social lives provided that it is kept under
control. CONCLUSIONS: This study sheds light on the Chinese adolescents' own
understandings and interpretations of their drinking. Our findings suggest that
interventions aimed to curtail underage drinking need to reflect social and
cultural contexts within which alcohol comes into play and importantly, consider
social environments that are conducive to underage drinking.
PMID- 26440774
TI - Overlap in attitudes to policy measures on alcohol, tobacco and illegal drugs.
AB - BACKGROUND: Effective alcohol, tobacco and illegal drug policies reduce the harm
to users and third parties. Knowledge about determinants and interrelations
between attitudes held by the general public to different types of policy
measures can benefit policy-makers who aim to increase acceptance for effective
policy. The present study describes the level of support for various policy
measures held by the general public, and investigates the association between
attitudes to policy measures on alcohol, tobacco and illegal drug. METHODS: A
sample of the Norwegian general population aged 16-64 (N=1803) was interviewed by
telephone. Respondents reported demographic information, personal substance use
and attitudes to various policy measures. Associations between attitudes were
assessed with correlation and regression analysis. RESULTS: Associations between
attitudes were strongest for similar policy measures across substance groups
(e.g. tax increases on alcohol and tobacco). There was a weaker association
between attitudes to different policy measures aimed at the same substance (e.g.
tax increase on alcohol and campaigns on alcohol). CONCLUSION: The degree to
which people approve or disapprove of the use of particular types of policy
measures is irrespective of the targeted substance.
PMID- 26440775
TI - Body Mass Index Underestimates Adiposity in Persons With Multiple Sclerosis.
AB - OBJECTIVES: To examine the relation between body mass index (BMI) and adiposity
assessed by dual-energy x-ray absorptiometry in persons with multiple sclerosis
(MS) and non-MS controls as well as to determine the accuracy of standard and
alternate BMI thresholds for obesity. DESIGN: Cross-sectional. SETTING:
University research laboratory. PARTICIPANTS: The sample included persons with MS
(n=235) and controls (n=53) (N=288). INTERVENTIONS: Not applicable. MAIN OUTCOME
MEASURES: Main outcome measures included BMI, whole body soft tissue composition
(ie, percent body fat [%BF], fat mass, and lean soft tissue mass), bone mineral
content, and bone mineral density. RESULTS: We observed significant strong
associations between BMI and sex-specific %BF in persons with MS and non-MS
controls, and BMI explained ~40% of the variance in %BF in both MS and control
samples. Receiver operating characteristic curve analyses indicated that the
standard BMI threshold for obesity (ie, 30kg/m(2)) had excellent specificity (93%
100%) but poor sensitivity (37%-44%) in persons with MS and non-MS controls. The
BMI threshold that best identified %BF-defined obesity was 24.7kg/m(2) in the MS
sample and 25.1kg/m(2) in the control sample. CONCLUSIONS: We determined a strong
association between BMI and adiposity; however, the current BMI threshold for
classifying obesity underestimates true adiposity in persons with MS. A similar
relation was observed between BMI and obesity in non-MS controls. The non-MS
sample included primarily middle-aged women, and similar BMI-%BF
misclassifications have been reported in these samples.
PMID- 26440776
TI - Clinical Course and Prognostic Factors in Conservatively Managed Carpal Tunnel
Syndrome: A Systematic Review.
AB - OBJECTIVE: To summarize the available evidence regarding the course of symptoms
and prognostic factors in patients with diagnosed carpal tunnel syndrome (CTS)
who are treated conservatively. DATA SOURCES: Computerized databases, reference
checking, and experts in the field were used to identify studies for inclusion in
the review. STUDY SELECTION: Multiple reviewers were used to identify studies
which included adults (aged >=18y) diagnosed with CTS in either a clinical
setting or population setting. The study must have observed the course of CTS
over at least a 6-week period in patients receiving no treatment or usual care
that included conservative (nonsurgical) treatments. The design was of a
longitudinal cohort study with either prospective or retrospective data
collection. There were no language restrictions, and none of the research
identified was only reported in abstract form. DATA EXTRACTION: Methodological
bias was assessed using the Quality in Prognosis Studies tool. A high risk of
bias (predominantly relating to study attrition, confounding, and/or statistical
analysis and reporting) was judged to be present in 8 studies. Designs showed
wide variability with respect to characteristics of the included population,
definition of CTS, assessment of prognostic factors, types of interventions
provided, and types of outcome measures applied. This prevented pooled estimates
from being produced. DATA SYNTHESIS: A negative outcome at 3 years' follow-up of
conservatively treated participants ranged from 23% to 89%. Four included studies
observed the rate of surgical intervention after initial conservative management
and found this to be 57% to 66%. Evidence regarding factors predicting the
negative outcome of no treatment or conservative treatment was graded, taking
into account the number of studies evaluating the factor, the methodological
quality of these studies, and the consistency of the available evidence. There
was 100% agreement in at least 3 cohorts with a medium or high risk of bias that
symptom duration, a positive Phalen's test, and thenar wasting were associated
with a negative outcome of conservative management; however, not all results were
statistically significant, and hence the overall judgment remained inconclusive.
CONCLUSIONS: Results of this review should be treated with caution because of the
heterogeneity of studies and the risks of bias identified. However, the course of
CTS appears variable, and poor prognosis may be predicted by a longer symptom
duration, a positive Phalen's test, and thenar wasting.
PMID- 26440777
TI - Systematic Review and Meta-Analysis of the Effects of Exercise for Those With
Cancer-Related Lymphedema.
AB - OBJECTIVES: To evaluate the effects of exercise on cancer-related lymphedema and
related symptoms, and to determine the need for those with lymphedema to wear
compression during exercise. DATA SOURCES: CINAHL, Cochrane, EBSCOhost, MEDLINE,
PubMed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health
Source, ScienceDirect, and SPORTDiscus databases were searched for trials
published before January 1, 2015. STUDY SELECTION: Randomized and nonrandomized
controlled trials and single-group pre-post studies published in English were
included. Twenty-one (exercise) and 4 (compression and exercise) studies met
inclusion criteria. DATA EXTRACTION: Data were extracted into tabular format
using predefined data fields by 1 reviewer and assessed for accuracy by a second
reviewer. Study quality was evaluated using the Effective Public Health Practice
Project Quality Assessment Tool. DATA SYNTHESIS: Data were pooled using a random
effects model to assess the effects of acute and long-term exercise on lymphedema
and lymphedema-associated symptoms, with subgroup analyses for exercise mode and
intervention length. There was no effect of exercise (acute or intervention) on
lymphedema or associated symptoms, with standardized mean differences from all
analyses ranging between -0.2 and 0.1 (P values >=.22). Findings from subgroup
analyses for exercise mode (aerobic, resistance, mixed, other) and intervention
duration (>12wk or <=12wk) were consistent with these findings-that is, no effect
on lymphedema or associated symptoms. There were too few studies evaluating the
effect of compression during regular exercise to conduct a meta-analysis.
CONCLUSIONS: Individuals with secondary lymphedema can safely participate in
progressive, regular exercise without experiencing a worsening of lymphedema or
related symptoms. However, there is insufficient evidence to support or refute
the current clinical recommendation to wear compression garments during regular
exercise.
PMID- 26440778
TI - Immunohistochemical analysis for G protein in the olfactory organs of soft
shelled turtle, Pelodiscus sinensis.
AB - In turtles, the epithelia lining the upper and lower chambers of the nasal cavity
project axons to the ventral and dorsal parts of the olfactory bulbs,
respectively. In a semi-aquatic soft-shelled turtle, Pelodiscus sinensis, more
than 1,000 odorant receptor genes have been found, but it is not known where they
are expressed. In this study, we aimed to clarify the distribution of cells
expressing these genes in the olfactory organs of soft-shelled turtles.
Immunoreactions for the Galphaolf, the alpha subunit of G protein coupled to the
odorant receptors, were detected on the surface of epithelia lining both the
upper and lower chambers of the nasal cavity. The receptor cells in the
epithelium of both chambers possessed cilia on the tip of their dendrites,
whereas microvillous, non-ciliated, receptor cells were not found. These data
suggest that the odorant receptor genes are expressed by the ciliated receptor
cells in the upper and lower chamber epithelia. Precise location of the
vomeronasal epithelium is not known at present.
PMID- 26440779
TI - Disappearing Enantiomorphs: Single Handedness in Racemate Crystals.
AB - Although crystallization is the most important method for the separation of
enantiomers of chiral molecules in the chemical industry, the chiral recognition
involved in this process is poorly understood at the molecular level. We report
on the initial steps in the formation of layered racemate crystals from a racemic
mixture, as observed by STM at submolecular resolution. Grown on a copper single
crystal surface, the chiral hydrocarbon heptahelicene formed chiral racemic
lattice structures within the first layer. In the second layer, enantiomerically
pure domains were observed, underneath which the first layer contained
exclusively the other enantiomer. Hence, the system changed from a 2D racemate
into a 3D racemate with enantiomerically pure layers after exceeding monolayer
saturation coverage. A chiral bias in form of a small enantiomeric excess
suppressed the crystallization of one double-layer enantiomorph so that the pure
minor enantiomer crystallized only in the second layer.
PMID- 26440780
TI - Seizures, Takotsubo syndrome, and sudden unexpected death in epilepsy: A still
puzzling triangle.
PMID- 26440781
TI - A glycemia-structured population model.
AB - Structured models are population models in which the individuals are
characterized with respect to the value of some variable of interest, called the
structure variable. In the present paper, we propose a glycemia-structured
population model, based on a linear partial differential equation with variable
coefficients. The model is characterized by three rate functions: a new-adult
population glycemic profile, a glycemia-dependent mortality rate and a glycemia
dependent average worsening rate. First, we formally analyze some properties of
the solution, the transient behavior and the equilibrium distribution. Then, we
identify the key parameters and functions of the model from real-life data and we
hypothesize some plausible modifications of the rate functions to obtain a more
beneficial steady-state behavior. The interest of the model is that, while it
summarizes the evolution of diabetes in the population in a completely different
way with respect to previously published Monte Carlo aggregations of individual
based models, it does appear to offer a good approximation of observed reality
and of the features expected in the clinical setting. The model can offer
insights in pharmaceutical research and be used to assess possible public health
intervention strategies.
PMID- 26440782
TI - Chromatographic fingerprint similarity analysis for pollutant source
identification.
AB - In the present study, a similarity analysis method was proposed to evaluate the
source-sink relationships among environmental media for polybrominated diphenyl
ethers (PBDEs), which were taken as the representative contaminants.
Chromatographic fingerprint analysis has been widely used in the fields of
natural products chemistry and forensic chemistry, but its application to
environmental science has been limited. We established a library of various
sources of media containing contaminants (e.g., plastics), recognizing that the
establishment of a more comprehensive library allows for a better understanding
of the sources of contamination. We then compared an environmental complex
mixture (e.g., sediment, soil) with the profiles in the library. These
comparisons could be used as the first step in source tracking. The cosine
similarities between plastic and soil or sediment ranged from 0.53 to 0.68,
suggesting that plastic in electronic waste is an important source of PBDEs in
the environment, but it is not the only source. A similarity analysis between
soil and sediment indicated that they have a source-sink relationship. Generally,
the similarity analysis method can encompass more relevant information of complex
mixtures in the environment than a profile-based approach that only focuses on
target pollutants. There is an inherent advantage to creating a data matrix
containing all peaks and their relative levels after matching the peaks based on
retention times and peak areas. This data matrix can be used for source
identification via a similarity analysis without quantitative or qualitative
analysis of all chemicals in a sample.
PMID- 26440783
TI - Shadows of anyons and the entanglement structure of topological phases.
AB - The low-temperature dynamics of quantum systems are dominated by the low-energy
eigenstates. For two-dimensional systems in particular, exotic phenomena such as
topological order and anyon excitations can emerge. While a complete low-energy
description of strongly correlated systems is hard to obtain, essential
information about the elementary excitations is encoded in the eigenvalue
structure of the quantum transfer matrix. Here we study the transfer matrix of
topological quantum systems using the tensor network formalism and demonstrate
that topological quantum order requires a particular type of 'symmetry breaking'
for the fixed point subspace. We also relate physical anyon excitations to domain
wall excitations at the level of the transfer matrix. This formalism enables us
to determine the structure of the topological sectors in two-dimensional gapped
phases very efficiently, therefore opening novel avenues for studying fundamental
questions related to anyon condensation and confinement.
PMID- 26440784
TI - Host Manipulation by Parasites: A Look Back Before Moving Forward.
AB - The ability to manipulate host behaviour is among the most fascinating and best
studied adaptations of parasites. In this opinion article, we highlight trends
and biases in the study of this phenomenon that may cloud or limit our
understanding of its evolution. For instance, reviews and theoretical studies
have shown a disproportionately sharp increase in the past decade relative to
empirical studies. We also discuss taxonomic biases in the host-parasite systems
investigated, as well as recent declines in the use of experimental infections
and in the proportion of these systems in which fitness benefits for the
parasites have been confirmed. We finish this opinion article by offering
recommendations for the continued success of research in this area.
PMID- 26440785
TI - Parasite-Parasite Interactions in the Wild: How To Detect Them?
AB - Inter-specific interactions between parasites impact on parasite intra-host
dynamics, host health, and disease management. Identifying and understanding
interaction mechanisms in the wild is crucial for wildlife disease management. It
is however complex because several scales are interlaced. Parasite-parasite
interactions are likely to occur via mechanisms at the within-host level, but
also at upper levels (host population and community). Furthermore, interactions
occurring at one level of organization spread to upper levels through cascade
effects. Even if cascade effects are important confounding factors, we argue that
we can also benefit from them because upper scales often provide a way to survey
a wider range of parasites at lower cost. New protocols and theoretical studies
(especially across scales) are necessary to take advantage of this opportunity.
PMID- 26440786
TI - Induction, Propagation, and Activity of Host Nitric Oxide: Lessons from
Leishmania Infection.
AB - The production of nitric oxide (NO) by the inducible NO synthase (iNOS) is a key
defense mechanism against intracellular pathogens such as Leishmania. Numerous
studies have investigated the antimicrobial properties of this small molecule in
vitro but its precise mode of action during Leishmania infection in vivo is still
unclear. In this review, we discuss how iNOS is induced in infected tissues and
how NO acts to control the expansion of Leishmania parasites and limit tissue
damage resulting from the infection. We highlight recently described mechanisms
that result in widespread iNOS expression in infected tissues. We also discuss
how the collective production and subsequent diffusion of NO generates an
antimicrobial milieu that promotes parasite control at the tissue level.
PMID- 26440787
TI - Born to be Wild--Don't Forget the Invertebrates.
PMID- 26440789
TI - Life without a Host Cell: What is Cryptosporidium?
AB - Cryptosporidium is a parasite responsible for widespread disease in livestock and
humans. Recent phylogenetic reclassification of Cryptosporidium from a coccidian
to a gregarine dictates an urgent need to reconsider the biology and behavior of
this parasite. Overwhelming data now confirm that, like its close relatives,
Cryptosporidium is a facultatively epicellular apicomplexan that is able to
multiply in a host cell-free environment. We complement the latest phylogenetic
and taxonomic proposals with advances in our understanding of Cryptosporidium's
biology, with particular focus on in vitro studies that have characterized the
development of Cryptosporidium stages in the absence of host cells. Opportunities
to revisit in vivo infections are discussed and questions about the
Cryptosporidium host cell-free life cycle that remain unanswered highlighted.
PMID- 26440788
TI - Methods for Quantification of Soil-Transmitted Helminths in Environmental Media:
Current Techniques and Recent Advances.
AB - Limiting the environmental transmission of soil-transmitted helminths (STHs),
which infect 1.5 billion people worldwide, will require sensitive, reliable, and
cost-effective methods to detect and quantify STHs in the environment. We review
the state-of-the-art of STH quantification in soil, biosolids, water, produce,
and vegetation with regard to four major methodological issues: environmental
sampling; recovery of STHs from environmental matrices; quantification of
recovered STHs; and viability assessment of STH ova. We conclude that methods for
sampling and recovering STHs require substantial advances to provide reliable
measurements for STH control. Recent innovations in the use of automated image
identification and developments in molecular genetic assays offer considerable
promise for improving quantification and viability assessment.
PMID- 26440790
TI - Commit and Transmit: Molecular Players in Plasmodium Sexual Development and
Zygote Differentiation.
AB - During each cycle of asexual endomitotic division in erythrocytes, the malaria
parasite makes a fundamental and crucial decision: to continue to invade and
proliferate or to differentiate into gametocytes ready for continuation of sexual
development. The proteins and regulatory pathways involved in Plasmodium sexual
development have been of great interest in recent years as targets for blocking
malaria transmission. However, the 'Holy Grail', the master switch orchestrating
asexual-to-sexual commitment and further differentiation, has remained elusive -
until now. Here we highlight the recent studies identifying the epigenetic and
transcriptional master regulators of sexual commitment and discuss the key
players in reversible phosphorylation pathways involved in sexual and zygote
differentiation.
PMID- 26440791
TI - A Gamma-Knife-Enabled Mouse Model of Cerebral Single-Hemisphere Delayed Radiation
Necrosis.
AB - PURPOSE: To develop a Gamma Knife-based mouse model of late time-to-onset,
cerebral radiation necrosis (RN) with serial evaluation by magnetic resonance
imaging (MRI) and histology. METHODS AND MATERIALS: Mice were irradiated with the
Leksell Gamma Knife(r) (GK) PerfexionTM (Elekta AB; Stockholm, Sweden) with total
single-hemispheric radiation doses (TRD) of 45- to 60-Gy, delivered in one to
three fractions. RN was measured using T2-weighted MR images, while confirmation
of tissue damage was assessed histologically by hematoxylin & eosin, trichrome,
and PTAH staining. RESULTS: MRI measurements demonstrate that TRD is a more
important determinant of both time-to-onset and progression of RN than
fractionation. The development of RN is significantly slower in mice irradiated
with 45-Gy than 50- or 60-Gy, where RN development is similar. Irradiated mouse
brains demonstrate all of the pathologic features observed clinically in patients
with confirmed RN. A semi-quantitative (0 to 3) histologic grading system,
capturing both the extent and severity of injury, is described and illustrated.
Tissue damage, as assessed by a histologic score, correlates well with total
necrotic volume measured by MRI (correlation coefficient = 0.948, with p<0.0001),
and with post-irradiation time (correlation coefficient = 0.508, with p<0.0001).
CONCLUSIONS: Following GK irradiation, mice develop late time-to-onset cerebral
RN histology mirroring clinical observations. MR imaging provides reliable
quantification of the necrotic volume that correlates well with histologic score.
This mouse model of RN will provide a platform for mechanism of action studies,
the identification of imaging biomarkers of RN, and the development of clinical
studies for improved mitigation and neuroprotection.
PMID- 26440793
TI - Tumor DNA Index and alpha-Fetoprotein Level Define Outcome following Liver
Transplantation for Advanced Hepatocellular Carcinoma.
AB - BACKGROUND: Patients with hepatocellular carcinoma (HCC) beyond the Milan
criteria are expected to have inferior outcome after liver transplantation (LT)
and are therefore currently not considered for LT in many countries. The purpose
of this study was to identify predictive factors for overall survival following
LT for HCC that may support the Milan criteria in the selection of appropriate
transplant candidates. METHODS: Clinicopathological data on 364 patients with HCC
who underwent LT between 1989 and 2010 were retrospectively evaluated. Predictors
of overall survival in the entire cohort as well as in subsets of patients within
(n = 214) and beyond (n = 150) the Milan criteria were analyzed. RESULTS:
Multivariate analysis in the entire cohort identified DNA index >1.5 (p <
0.0001), alpha-fetoprotein level (AFP) >200 ng/ml (p = 0.005), and HCC beyond the
Milan criteria (p = 0.002) to be associated with worse overall survival. In
patients within the Milan criteria (median survival: 170 months), DNA index >1.5
(p < 0.0001) was the only predictor of worse overall survival in multivariate
analysis. In patients beyond the Milan criteria (median survival: 44 months), DNA
index >1.5, AFP >200 ng/ml, microvascular invasion, patient age >60 years, and
DNA index >1.5 concomitant with AFP >200 ng/ml were associated with worse overall
survival in univariate analysis. Multivariate analysis identified DNA index >1.5
concomitant with AFP >200 ng/ml (p < 0.0001) as the only independent predictor of
worse overall survival. Consequently, patients beyond the Milan criteria with a
combined favorable DNA index <=1.5 and AFP <=200 ng/ml had a median survival (147
months) comparable to that of patients within the Milan criteria. CONCLUSIONS:
DNA index and AFP level predict overall survival following LT in patients with
advanced HCC beyond the Milan criteria. A combined assessment of these markers
during the evaluation of transplant candidates can contribute to the selection of
patients with HCC who may benefit from LT independently of their tumor burden.
PMID- 26440792
TI - Preterm infants' behaviors and skin conductance responses to nurse handling in
the NICU.
AB - Stress response patterns are indicative of the neonate's unique ability to cope
with environmental demands and can be evaluated through autonomic and behavioral
response parameters. OBJECTIVE: To characterize stress responses during tactile
stimulation to standard nurse handling in the NICU, and their association with
severity of illness in preterm infants. METHODS: Thirty preterm neonates were
studied at postnatal day 4-5 during standard nurse caregiving. Heart rate (HR),
respiratory rate (RR), skin conductance responses per second (SCR/s), and
NIDCAP(r) stress behaviors were recorded before and during care. Non-parametric
tests were used to assess differences from before to during care. Pearson's
correlations were used to determine the association of biological and behavioral
variables to the score for neonatal acute physiology (SNAP), a severity of
illness index. RESULTS: HR, RR, SCR/s and NIDCAP(r) behaviors (motor and
attentional cues, and ability to self-console) increased from before to during
the care (p < 0.01). NIDCAP(r) behaviors showed a significant negative
association to the SNAP score (R = -0.45, p < 0.05). CONCLUSIONS: HR, RR, SCR/s
and NIDCAP(r) behaviors significantly increased during care. NIDCAP(r) stress
behaviors were influenced by the severity of illness of the infant, while SCR/s
was not influenced by severity of illness.
PMID- 26440794
TI - Passage-Based Bibliographic Coupling: An Inter-Article Similarity Measure for
Biomedical Articles.
AB - Biomedical literature is an essential source of biomedical evidence. To translate
the evidence for biomedicine study, researchers often need to carefully read
multiple articles about specific biomedical issues. These articles thus need to
be highly related to each other. They should share similar core contents,
including research goals, methods, and findings. However, given an article r, it
is challenging for search engines to retrieve highly related articles for r. In
this paper, we present a technique PBC (Passage-based Bibliographic Coupling)
that estimates inter-article similarity by seamlessly integrating bibliographic
coupling with the information collected from context passages around important
out-link citations (references) in each article. Empirical evaluation shows that
PBC can significantly improve the retrieval of those articles that biomedical
experts believe to be highly related to specific articles about gene-disease
associations. PBC can thus be used to improve search engines in retrieving the
highly related articles for any given article r, even when r is cited by very few
(or even no) articles. The contribution is essential for those researchers and
text mining systems that aim at cross-validating the evidence about specific gene
disease associations.
PMID- 26440795
TI - Delayed Wound Healing in Heat Stable Antigen (HSA/CD24)-Deficient Mice.
AB - BACKGROUND: Healthy individuals rarely have problems with wound healing. Most
skin lesions heal rapidly and efficiently within one to two weeks. However, many
medical and surgical complications can be attributed to deficiencies in wound
repair. Open wounds have lost the barrier that protects tissues from bacterial
invasion and allows the escape of vital fluids. Without expeditious healing,
infections become more frequent. The CD24 gene encodes a heavily-glycosylated
cell surface protein anchored to the membrane by phosphatidylinositol. CD24 plays
an important role in the adaptive immune response and controls an important
genetic checkpoint for homeostasis and autoimmune diseases in both mice and
humans. We have previously shown that overexpression of CD24 results in increased
proliferation and migration rates. AIM: To examine the role of CD24 in the wound
healing process. METHODS: An excisional model of wound healing was used and
delayed wound healing was studied in genetically modified heat stable antigen
(HSA/CD24)-deficient mice (HSA-/-) compared to wild-type (WT) mice. RESULTS:
Large full-thickness skin wounds, excised on the back of mice, exhibited a
significant delay in the formation of granulation tissue, and in wound closure
when compared to their WTHSA+/+ littermates. Wounds were histologically analyzed
and scored, based on the degree of cellular invasion, granulation tissue
formation, vascularity, and re-epithelialization. Additionally, in stitched
wounds, the HSA-/- mice failed to maintain their stitches; they did not hold and
fell already 24 hours, revealing erythematous wound fields. Re-expression of HSA,
delivered by lentivirus, restored the normal healing phenotype, within 24 hours
post-injury, and even improved the healing in WT, and in BalbC mice. CONCLUSIONS:
Delayed wound-healing in the absence of HSA/CD24 suggests that CD24 plays an
important role in this process. Increased expression of CD24, even in the normal
state, may be used to enhance wound repair.
PMID- 26440797
TI - Quality of life among former Soviet Union and Israeli origin methadone users.
AB - A common treatment intervention for heroin addiction is methadone maintenance. In
recent years a wider perspective has been adapted to understand and evaluate
addiction through quality of life. This article examines quality of life
conditions of 170 male former Soviet Union and Israeli origin drug users in
methadone maintenance and provides an understanding of conditions linked to the
World Health Organization Quality of Life project's best available techniques
reference document. Having a partner or spouse and less chronic illness are
positive factors affecting quality of life regardless of country of origin.
Israeli born drug users reported better quality of life based on their
psychological health and environment domain responses; no difference was found
for the physical health and social relationship domains of the Israeli and former
Soviet Union origin males. Because heroin addiction is a chronic and relapsing
illness, one of the goals of methadone maintenance is to address patients' health
status from a broad perspective. Based on clinical observations, the treatment of
special populations may be enhanced if their particular needs are considered and
met. Quality of life factors are relevant for assessing high risk groups,
including those from different ethnic origins, in poor physical and psychological
health, their treatment and personal adjustment, and their service personnel
training needs.
PMID- 26440796
TI - Development of Human-Like scFv-Fc Neutralizing Botulinum Neurotoxin E.
AB - BACKGROUND: Botulinum neurotoxins (BoNTs) are considered to be the most toxic
substances known on earth and are responsible for human botulism, a life
threatening disease characterized by flaccid muscle paralysis that occurs
naturally by food-poisoning or colonization of the gastrointestinal tract by BoNT
producing clostridia. BoNTs have been classified as category A agent by the
Centers of Disease Control and Prevention (CDC) and are listed among the six
agents with the highest risk to be used as bioweapons. Neutralizing antibodies
are required for the development of effective anti-botulism therapies to deal
with the potential risk of exposure. RESULTS: In this study, a macaque (Macaca
fascicularis) was immunized with recombinant light chain of BoNT/E3 and an immune
phage display library was constructed. After a multi-step panning, several
antibody fragments (scFv, single chain fragment variable) with nanomolar
affinities were isolated, that inhibited the endopeptidase activity of pure
BoNT/E3 in vitro by targeting its light chain. Furthermore, three scFv were
confirmed to neutralize BoNT/E3 induced paralysis in an ex vivo mouse phrenic
nerve-hemidiaphragm assay. The most effective neutralization (20LD50/mL, BoNT/E3)
was observed with scFv ELC18, with a minimum neutralizing concentration at 0.3
nM. Furthermore, ELC18 was highly effective in vivo when administered as an scFv
Fc construct. Complete protection of 1LD50 BoNT/E3 was observed with 1.6 ng/dose
in the mouse flaccid paralysis assay. CONCLUSION: These scFv-Fcs antibodies are
the first recombinant antibodies neutralizing BoNT/E by targeting its light
chain. The human-like nature of the isolated antibodies is predicting a good
tolerance for further clinical development.
PMID- 26440798
TI - Voluntary Exercise Prevents Oxidative Stress in the Brain of Phenylketonuria
Mice.
AB - BACKGROUND: High phenylalanine levels in phenylketonuria (PKU) have been
associated with brain oxidative stress and amino acid imbalance. Exercise has
been shown to improve brain function in hyperphenylalaninemia and
neurodegenerative diseases. This study aimed to verify the effects of exercise on
coordination and balance, plasma and brain amino acid levels, and brain oxidative
stress markers in PKU mice. METHODS: Twenty wild-type (WT) and 20 PAH(enu2) (PKU)
C57BL/6 mice were placed in cages with (exercise, Exe) or without (sedentary,
Sed) running wheels during 53 days. At day 43, a balance beam test was performed.
Plasma and brain were collected for analyses of amino acid levels and the
oxidative stress parameters superoxide dismutase (SOD) activity, sulfhydryl and
reduced glutathione (GSH) contents, total radical-trapping antioxidant potential
(TRAP), and total antioxidant reactivity (TAR). RESULTS: SedPKU showed poor
coordination (p < 0.001) and balance (p < 0.001), higher plasma and brain
phenylalanine (p < 0.001), and increased brain oxidative stress (p < 0.05) in
comparison to SedWT. ExePKU animals ran less than ExeWT (p = 0.018). Although no
improvement was seen in motor coordination and balance, exercise in PKU restored
SOD, sulfhydryl content, and TRAP levels to controls. TAR levels were increased
in ExePKU in comparison to SedPKU (p = 0.012). Exercise decreased plasma and
brain glucogenic amino acids in ExePKU, but did not change plasma and brain
phenylalanine in both WT and PKU. CONCLUSIONS: Exercise prevents oxidative stress
in the brain of PKU mice without modifying phenylalanine levels. Hence, exercise
positively affects the brain, demonstrating its value as an intervention to
improve brain quality in PKU.
PMID- 26440799
TI - Fine mapping of qhir8 affecting in vivo haploid induction in maize.
AB - KEY MESSAGE: The QTL qhir8 affecting in vivo haploid induction in maize was
mapped to a 789 kb region, embryo abortion rate and segregation ratios were
analyzed, linkage markers for MAS were developed. The doubled-haploid (DH)
technology has become an important tool for line development in modern maize
breeding. However, the genetic basis of haploid induction remains elusive. In
previous QTL mapping research, qhir8 besides qhir1 significantly affected haploid
induction rate (HIR). Our objective was to fine map qhir8 and assess its effect
on HIR, segregation distortion (SD) and embryo abortion (EmA). A total of 3989 F2
plants from the cross of inducers CAUHOI and UH400 were screened for recombinants
in the qhir8 region. F2 plants and F3 plants from selfing progenies of 34
recombinant F2 plants were evaluated for HIR, SD and EmA. In parallel, we
developed 31 new markers providing good coverage of the qhir8 region. We
confirmed that qhir8 has an increasing effect on HIR and EmA, but not on SD.
Moreover, we successfully narrowed down the qhir8 locus to a 789 kb region
flanked by markers 4292232 and umc1867.
PMID- 26440800
TI - What do metabolic rates tell us about thermal niches? Mechanisms driving crayfish
distributions along an altitudinal gradient.
AB - Humans are rapidly altering thermal landscapes, so a central challenge to
organismal ecologists is to better understand the thermal niches of ectotherms.
However, there is much disagreement over how we should go about this. Some
ecologists assume that a statistical model of abundance as a function of habitat
temperature provides a sufficient approximation of the thermal niche, but
ecophysiologists have shown that the relationship between fitness and temperature
can be complicated, and have stressed the need to elucidate the causal mechanisms
underlying the response of species to thermal change. Towards this end, we
studied the distribution of two crayfishes, Euastacus woiwuru and Euastacus
armatus, along an altitudinal gradient, and for both species conducted
experiments to determine the temperature-dependence of: (1) aerobic scope (the
difference between maximum and basal metabolic rate; purported to be a proxy of
the thermal niche); and (2) burst locomotor performance (primarily fuelled using
anaerobic pathways). E. woiwuru occupied cooler habitats than E. armatus, but we
found no difference in aerobic scope between these species. In contrast,
locomotor performance curves differed significantly and strongly between species,
with peak locomotor performances of E. woiwuru and E. armatus occurring at ~10
and ~18 degrees C, respectively. Crayfish from different thermal landscapes may
have similar aerobic thermal performance curves but different anaerobic thermal
performance curves. Our results support a growing body of literature implying
different components of ectotherm fitness have different thermal performance
curves, and further challenge our understanding of the ecology and evolution of
thermal niches.
PMID- 26440801
TI - Local adaptation to parasite selective pressure: comparing three congeneric co
occurring hosts.
AB - Local adaptation may optimize an organism's investment in defenses in response to
the risk of infection by spatially heterogeneous parasites and other natural
enemies. However, local adaptation may be constrained if recruitment is decoupled
from selective pressure experienced by the parent generation. We predicted that
the ability of three intertidal littorinid snail species to defend against
trematode parasites would depend on prior levels of population exposure to
parasites and on larval dispersal mode, a proxy for population openness. In a
common garden experiment, for two snail species with direct development and
localized recruitment (Littorina obtusata and Littorina saxatilis), hosts from
sites with high trematode infection risk were less susceptible to infection than
hosts from low-risk sites. However, this relationship was not apparent for a
third host species with broadcast larvae (Littorina littorea), suggesting that
broad larval dispersal can impede local adaptation; alternatively, the lack of
response in this species could owe to other factors that limited experimental
infection in this host. Our findings support that locally recruiting hosts can
adapt their defenses to scale with localized infection risk.
PMID- 26440802
TI - Intrinsic surface dipole in topological insulators.
AB - We calculate the local density of states of two prototypical topological
insulators (Bi2Se3 and Bi2Te2Se) as a function of distance from the surface
within density functional theory. We find that, in the absence of disorder or
doping, there is a 2 nm thick surface dipole the origin of which is the
occupation of the topological surface states above the Dirac point. As a
consequence, the bottom of the conduction band is bent upward by about 75 meV
near the surface, and there is a hump-like feature associated with the top of the
valence band. We expect that band bending will occur in all pristine topological
insulators as long as the Fermi level does not cross the Dirac point. Our results
show that topological insulators are intrinsic Schottky barrier solar cells.
PMID- 26440804
TI - Synchronous Ipsilateral Parotid Tumors with Cytologic-Histologic Correlation.
AB - Synchronous ipsilateral tumor formation within a major salivary gland is a very
rare event. In this case, a 54-year-old female tobacco smoker presented with a
slowly enlarging left parotid gland. Computed tomography of the neck demonstrated
a solid mass superficial to a cystic mass in the deep lobe of the gland.
Ultrasound-guided fine needle aspiration yielded oncocytic cells, lymphoid cells,
and granular debris along with rare cohesive groups of basaloid cells.
Parotidectomy was performed, and the resected gland was found to contain two
adjacent but distinct masses. One mass, a predominantly solid, well-circumscribed
lesion composed of ribbons of double-layered oncocytic cells and a lymphoid
stroma with germinal center formation, was a Warthin tumor. The other mass, a
predominantly cystic lesion composed of cords and nests of basaloid cells with
associated deposits of basement membrane-like material, was a basal cell adenoma
of the membranous type. To our knowledge, this is the first reported case of
synchronous Warthin tumor and basal cell adenoma of the parotid gland with
cytologic-histologic correlation attributable to each tumor.
PMID- 26440803
TI - The REporting of studies Conducted using Observational Routinely-collected health
Data (RECORD) statement.
AB - Routinely collected health data, obtained for administrative and clinical
purposes without specific a priori research goals, are increasingly used for
research. The rapid evolution and availability of these data have revealed issues
not addressed by existing reporting guidelines, such as Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE). The REporting of
studies Conducted using Observational Routinely collected health Data (RECORD)
statement was created to fill these gaps. RECORD was created as an extension to
the STROBE statement to address reporting items specific to observational studies
using routinely collected health data. RECORD consists of a checklist of 13 items
related to the title, abstract, introduction, methods, results, and discussion
section of articles, and other information required for inclusion in such
research reports. This document contains the checklist and explanatory and
elaboration information to enhance the use of the checklist. Examples of good
reporting for each RECORD checklist item are also included herein. This document,
as well as the accompanying website and message board (http://www.record
statement.org), will enhance the implementation and understanding of RECORD.
Through implementation of RECORD, authors, journals editors, and peer reviewers
can encourage transparency of research reporting.
PMID- 26440805
TI - Huperzine A Alleviates Oxidative Glutamate Toxicity in Hippocampal HT22 Cells via
Activating BDNF/TrkB-Dependent PI3K/Akt/mTOR Signaling Pathway.
AB - Oxidative glutamate toxicity is involved in diverse neurological disorders
including epilepsy and ischemic stroke. Our present work aimed to assess
protective effects of huperzine A (HupA) against oxidative glutamate toxicity in
a mouse-derived hippocampal HT22 cells and explore its potential mechanisms. Cell
survival and cell injury were analyzed by MTT method and LDH release assay,
respectively. The production of ROS was measured by detection kits. Protein
expressions of BDNF, phosphor-TrkB (p-TrkB), TrkB, phosphor-Akt (p-Akt), Akt,
phosphor-mTOR (p-mTOR), mTOR, phosphor-p70s6 (p-p70s6) kinase, p70s6 kinase, Bcl
2, Bax, and beta-actin were assayed via Western blot analysis. Enzyme-linked
immunosorbent assay was employed to measure the contents of nerve growth factor,
brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin
4 (NT-4). Our findings illustrated 10 MUM HupA for 24 h significantly protected
HT22 from cellular damage and suppressed the generation of ROS. Additionally,
after treating with LY294002 or wortmannin [the selective inhibitors of
phosphatidylinositol 3 kinase (PI3K)], HupA dramatically prevented the down
regulations of p-Akt, p-mTOR, and p-p70s6 kinase in HT22 cells under oxidative
toxicity. Furthermore, it was observed that the protein levels of BDNF and p-TrkB
were evidently enhanced after co-treatment with HupA and glutamate in HT22 cells.
The elevations of p-Akt and p-mTOR were abrogated under toxic conditions after
blockade of TrkB by TrkB IgG. Cellular apoptosis was significantly suppressed
(decreased caspase-3 activity and enhanced Bcl-2 protein level) after HupA
treatment. It was concluded that HupA attenuated oxidative glutamate toxicity in
murine hippocampal HT22 cells via activating BDNF/TrkB-dependent PI3K/Akt/mTOR
signaling pathway.
PMID- 26440806
TI - Role of the Outer Membrane Protein OprD2 in Carbapenem-Resistance Mechanisms of
Pseudomonas aeruginosa.
AB - We investigated the relationship between the outer membrane protein OprD2 and
carbapenem-resistance in 141 clinical isolates of Pseudomonas aeruginosa
collected between January and December 2013 from the First Affiliated Hospital of
Anhui Medical University in China. Agar dilution methods were employed to
determine the minimum inhibitory concentration of meropenem (MEM) and imipenem
(IMP) for P. aeruginosa. The gene encoding OprD2 was amplified from141 P.
aeruginosa isolates and analyzed by PCR and DNA sequencing. Differences between
the effects of IMPR and IMPS groups on the resistance of the P. aeruginosa were
observed by SDS-poly acrylamide gel electrophoresis (SDS-PAGE). Three resistance
types were classified in the 141 carbapenem-resistant P. aeruginosa (CRPA)
isolates tested, namely IMPRMEMR (66.7%), IMPRMEMS (32.6%), and IMPRMEMS (0.7%).
DNA sequencing revealed significant diverse gene mutations in the OprD2-encoding
gene in these strains. Thirty-four strains had large fragment deletions in the
OprD2gene, in 6 strains the gene contained fragment inserts, and in 96 resistant
strains, the gene featured small fragment deletions or multi-site mutations. Only
4 metallo-beta-lactamase strains and 1 imipenem-sensitive (meropenem-resistant)
strain showed a normal OprD2 gene. Using SDS-PAGE to detect the outer membrane
protein in 16 CRPA isolates, it was found that 10 IMPRMEMR strains and 5 IMPRMEMS
strains had lost the OprD2 protein, while the IMPSMEMR strain contained a normal
46-kDa protein. In conclusion, mutation or loss of the OprD2-encoding gene caused
the loss of OprD2, which further led to carbapenem-resistance of P. aeruginosa.
Our findings provide insights into the mechanism of carbapenem resistance in P.
aeruginosa.
PMID- 26440810
TI - Evaluation of Blood Glucose Meter Efficacy in an Antenatal Diabetes Clinic.
AB - BACKGROUND: The optimal treatment of diabetes in pregnancy requires accurate
measurement of blood glucose levels, in order to minimize adverse outcomes for
both mother and neonate. Self-monitoring of blood glucose is routinely used to
measure glycemic control and to assess whether treatment targets are being met;
however, the accuracy of blood glucose meters in pregnancy is unclear. MATERIALS
AND METHODS: Pregnant women with gestational, type 1, or type 2 diabetes mellitus
were eligible to participate. Nonfasting capillary blood glucose levels were
measured in duplicate using the BGStar((r)) (Sanofi, Sydney, Australia) and
FreeStyle Lite((r)) (Abbott, Sydney) blood glucose meters. Venous blood samples
were collected and analyzed for plasma glucose, hematocrit, and glycated
hemoglobin. Capillary blood glucose was compared with plasma glucose and further
assessed according to International Organization for Standardization (ISO)
15197:2013 standards. RESULTS: One hundred ten women were recruited, providing 96
samples suitable for analysis. The mean +/- SD laboratory plasma glucose level
was 4.6 +/- 1.4 mmol/L; the BGStar and FreeStyle Lite capillary blood glucose
values were 5.3 +/- 1.4 mmol/L and 5.0 +/- 1.3 mmol/L, respectively. Both meters
showed a positive bias (0.42 mmol/L for the FreeStyle Lite and 0.65 mmol/L for
the BGStar). Furthermore, neither meter fulfilled the ISO 15197:2013 standards,
and there was a nonsignificant improvement in meter performance at blood glucose
levels of <=4.2 mmol/L. Hematocrit did not affect the results of either blood
glucose meter. Clarke Error Grid analysis demonstrated that approximately 70% of
the results of both meters would lead to appropriate clinical action.
CONCLUSIONS: The BGStar and FreeStyle Lite blood glucose meters did not meet ISO
15197:2013 recommendations for blood glucose monitoring systems when assessed in
a population of women with diabetes in pregnancy. Clinicians should consider this
difference in blood glucose readings when making diabetes-related treatment
decisions.
PMID- 26440811
TI - Size- and shape-dependent phase diagram of In-Sb nano-alloys.
AB - Nano-scale alloy systems with at least one dimension below 100 nm have different
phase stabilities than those observed in the macro-scale systems due to a large
surface to volume ratio. We have used the semi-empirical thermodynamic modelling,
i.e. the CALPHAD method, to predict the phase equilibria of the In-Sb nano-scale
systems as a function of size and shape. To calculate the size- and shape
dependent phase diagram of the In-Sb system, we have added size-dependent surface
energy terms to the Gibbs energy expressions in the In-Sb thermodynamic database.
We estimated the surface energies of the solution phases and of the InSb
intermetallic phase using the Butler equation and DFT calculations, respectively.
A melting point and eutectic point depression were observed for both nanoparticle
and nanowire systems. The eutectic composition on the In-rich and Sb-rich sides
of the phase diagram shifted towards higher solubility. We believe that the phase
diagram of In-Sb nano-alloys is useful for an increased understanding of the
growth parameters and mechanisms of InSb nanostructures.
PMID- 26440812
TI - Tipping the Balance between Concerted versus Sequential Proton-Coupled Electron
Transfer.
AB - We use quantized molecular dynamics simulations to investigate the competition
between concerted and sequential proton-coupled electron-transfer (PCET) reaction
mechanisms in inorganic catalysts. By analyzing reactive nonadiabatic PCET
trajectories and computing both concerted and sequential rate constants, we
characterize various molecular features that govern inorganic PCET reactions,
including the solvent polarity, ligand-mediated electron-proton interactions, and
intrinsic proton-transfer (PT) energy barrier. Using atomistic simulations with
over 1200 atoms, we find that the symmetric iron biimidazoline system is
extremely biased toward the concerted mechanism because of the strong ligand
mediated electron-proton interaction and the short PT distance. However, by
investigating system-bath models in which electron-proton interactions are
shielded, which are representative of ruthenium terpyridylbenzoates and iron
(tetraphenylporphyrin)benzoates, we predict that a crossover between the
concerted and sequential PCET mechanisms may be possible either by increasing the
polarity of the solvent or by increasing the intrinsic PT energy barrier. In
addition, we predict the possibility of a crossover in the PCET mechanism by
directly varying the strength of the ligand-mediated electron-proton
interactions. The results presented here reveal new strategies for altering the
competition between the competing PCET mechanisms and design principles for
controlling PCET in catalytic systems.
PMID- 26440814
TI - Invasive Group A Streptococcal Infections in Children: A Nationwide Survey in
Finland.
AB - BACKGROUND: The incidence of invasive group A streptococcus (iGAS) infections
varies in time and geographically for unknown reasons. We performed a nationwide
survey to assess the population-based incidence rates and outcomes of children
with iGAS infections. METHODS: We collected data on patients from hospital
discharge registries and the electronic databases of microbiological laboratories
in Finland for the period 1996-2010. We then recorded the emm types or serotypes
of the strains. The study physician visited all university clinics and collected
the clinical data using the same data entry sheet. RESULTS: We identified 151
children with iGAS infection. Varicella preceded iGAS infection in 20% of cases
and fasciitis infection in 83% of cases. The annual incidence rate of iGAS
infection was 0.93 per 100,000 in 1996-2000, 1.80 in 2001-2005 and 2.50 in 2006
2010. The proportion of emm 1.0 or T1M1 strains peaked in 1996-2000 and again in
2006-2010, to 44% and 37% of all typed isolates. The main clinical diagnoses of
the patients were severe soft-tissue infection (46%), sepsis (28%), empyema
(10%), osteoarticular infection (9%) and primary peritonitis (5%). Severe pain
was the most typical symptom for soft-tissue infections. More than half of the
patients underwent surgery and received clindamycin. The readmission rate was 7%,
and the case fatality rate was 2%. CONCLUSIONS: The incidence rate of pediatric
iGAS infections tripled during our study. The increase was not, however, the
result of a change in the strain types causing iGAS. Varicella immunization would
likely have prevented a significant number of the cases.
PMID- 26440813
TI - Reductions in Cortico-Striatal Hyperconnectivity Accompany Successful Treatment
of Obsessive-Compulsive Disorder with Dorsomedial Prefrontal rTMS.
AB - Obsessive-compulsive disorder (OCD) is a disabling illness with high rates of
nonresponse to conventional treatments. OCD pathophysiology is believed to
involve abnormalities in cortico-striatal-thalamic-cortical circuits through
regions such as dorsomedial prefrontal cortex (dmPFC) and ventral striatum. These
regions may constitute therapeutic targets for neuromodulation treatments, such
as repetitive transcranial magnetic stimulation (rTMS). However, the
neurobiological predictors and correlates of successful rTMS treatment for OCD
are unclear. Here, we used resting-state functional magnetic resonance imaging
(fMRI) to identify neural predictors and correlates of response to 20-30 sessions
of bilateral 10 Hz dmPFC-rTMS in 20 treatment-resistant OCD patients, with 40
healthy controls as baseline comparators. A region of interest in the dmPFC was
used to generate whole-brain functional connectivity maps pre-treatment and post
treatment. Ten of 20 patients met the response criteria (?50% improvement on Yale
Brown Obsessive-Compulsive Scale, YBOCS); response to dmPFC-rTMS was sharply
bimodal. dmPFC-rTMS responders had higher dmPFC-ventral striatal connectivity at
baseline. The degree of reduction in this connectivity, from pre- to post
treatment, correlated to the degree of YBOCS symptomatic improvement. Baseline
clinical and psychometric data did not predict treatment response. In summary,
reductions in fronto-striatal hyperconnectivity were associated with treatment
response to dmPFC-rTMS in OCD. This finding is consistent with previous fMRI
studies of deep brain stimulation in OCD, but opposite to previous reports on
mechanisms of dmPFC-rTMS in major depression. fMRI could prove useful in
predicting the response to dmPFC-rTMS in OCD.
PMID- 26440815
TI - The Whole School, Whole Community, Whole Child model: a new approach for
improving educational attainment and healthy development for students.
AB - BACKGROUND: The Whole Child approach and the coordinated school health (CSH)
approach both address the physical and emotional needs of students. However, a
unified approach acceptable to both the health and education communities is
needed to assure that students are healthy and ready to learn. METHODS: During
spring 2013, the ASCD (formerly known as the Association for Supervision and
Curriculum Development) and the US Centers for Disease Control and Prevention
(CDC) convened experts from the field of education and health to discuss lessons
learned from implementation of the CSH and Whole Child approaches and to explore
the development of a new model that would incorporate the knowledge gained
through implementation to date. RESULTS: As a result of multiple discussions and
review, the Whole School, Whole Community, Whole Child (WSCC) approach was
developed. The WSCC approach builds upon the traditional CSH model and ASCD's
Whole Child approach to learning and promotes greater alignment between health
and educational outcomes. CONCLUSION: By focusing on children and youth as
students, addressing critical education and health outcomes, organizing
collaborative actions and initiatives that support students, and strongly
engaging community resources, the WSCC approach offers important opportunities
that will improve educational attainment and healthy development for students.
PMID- 26440817
TI - Lessons learned from the whole child and coordinated school health approaches.
AB - BACKGROUND: The new Whole School, Whole Community, Whole Child (WSCC) model,
designed to depict links between health and learning, is founded on concepts of
coordinated school health (CSH) and a whole child approach to education. METHODS:
The existing literature, including scientific articles and key publications from
national agencies and organizations, was reviewed and synthesized to describe (1)
the historical context for CSH and a whole child approach, and (2) lessons
learned from the implementation and evaluation of these approaches. RESULTS: The
literature revealed that interventions conducted in the context of CSH can
improve health-related and academic outcomes, as well as policies, programs, or
partnerships. Several structural elements and processes have proved useful for
implementing CSH and a whole child approach in schools, including use of school
health coordinators, school-level and district-level councils or teams;
systematic assessment and planning; strong leadership and administrative support,
particularly from school principals; integration of health-related goals into
school improvement plans; and strong community collaborations. CONCLUSIONS:
Lessons learned from years of experience with CSH and the whole child approaches
have applicability for developing a better understanding of the WSCC model as
well as maximizing and documenting its potential for impacting both health and
education outcomes.
PMID- 26440816
TI - Critical connections: health and academics.
AB - BACKGROUND: While it is a national priority to support the health and education
of students, these sectors must better align, integrate, and collaborate to
achieve this priority. This article summarizes the literature on the connection
between health and academic achievement using the Whole School, Whole Community,
and Whole Child (WSCC) framework as a way to address health-related barriers to
learning. METHODS: A literature review was conducted on the association between
student health and academic achievement. RESULTS: Most of the evidence examined
the association between student health behaviors and academic achievement, with
physical activity having the most published studies and consistent findings. The
evidence supports the need for school health services by demonstrating the
association between chronic conditions and decreased achievement. Safe and
positive school environments were associated with improved health behaviors and
achievement. Engaging families and community members in schools also had a
positive effect on students' health and achievement. CONCLUSIONS: Schools can
improve the health and learning of students by supporting opportunities to learn
about and practice healthy behaviors, providing school health services, creating
safe and positive school environments, and engaging families and community. This
evidence supports WSCC as a potential framework for achieving national
educational and health goals.
PMID- 26440818
TI - What have we learned from collaborative partnerships to concomitantly improve
both education and health?
AB - BACKGROUND: Collaborative partnerships are an essential means to concomitantly
improve both education outcomes and health outcomes among K-12 students. METHODS:
We describe examples of contemporaneous, interactive, and evolving partnerships
that have been implemented, respectively, by a national governmental health
organization, national nongovernmental education and health organizations, a
state governmental education organization, and a local nongovernmental health
organization that serves partner schools. RESULTS: Each of these partnerships
strategically built operational infrastructures that enabled partners to
efficiently combine their resources to improve student education and health.
CONCLUSIONS: To implement a Whole School, Whole Community, Whole Child Framework,
we need to purposefully strengthen, expand, and interconnect national, state, and
local collaborative partnerships and supporting infrastructures that
concomitantly can improve both education and health.
PMID- 26440819
TI - How the Whole School, Whole Community, Whole Child model works: creating greater
alignment, integration, and collaboration between health and education.
AB - BACKGROUND: The Whole School, Whole Community, Whole Child (WSCC) model calls for
greater collaboration across the community, school, and health sectors to meet
the needs and support the full potential of each child. This article reports on
how 3 states and 2 local school districts have implemented aspects of the WSCC
model through collaboration, leadership and policy creation, alignment, and
implementation. METHODS: We searched state health and education department
websites, local school district websites, state legislative databases, and
sources of peer-reviewed and gray literature to identify materials demonstrating
adoption and implementation of coordinated school health, the WSCC model, and
associated policies and practices in identified states and districts. We
conducted informal interviews in each state and district to reinforce the
document review. RESULTS: States and local school districts have been able to
strategically increase collaboration, integration, and alignment of health and
education through the adoption and implementation of policy and practice
supporting the WSCC model. Successful utilization of the WSCC model has led to
substantial positive changes in school health environments, policies, and
practices. CONCLUSIONS: Collaboration among health and education sectors to
integrate and align services may lead to improved efficiencies and better health
and education outcomes for students.
PMID- 26440820
TI - Placing students at the center: the Whole School, Whole Community, Whole Child
model.
AB - BACKGROUND: Students are the heart of the Whole School, Whole Community, Whole
Child (WSCC) model. Students are the recipients of programs and services to
ensure that they are healthy, safe, engaged, supported, and challenged and also
serve as partners in the implementation and dissemination of the WSCC model.
METHODS: A review of the number of students nationwide enjoying the 5 Whole Child
tenets reveals severe deficiencies while a review of student-centered approaches,
including student engagement and student voice, appears to be one way to remedy
these deficiencies. RESULTS: Research in both education and health reveals that
giving students a voice and engaging students as partners benefits them by
fostering development of skills, improvement in competence, and exertion of
control over their lives while simultaneously improving outcomes for their peers
and the entire school/organization. CONCLUSIONS: Creating meaningful roles for
students as allies, decision makers, planners, and consumers shows a commitment
to prepare them for the challenges of today and the possibilities of tomorrow.
PMID- 26440821
TI - Supporting the whole child through coordinated policies, processes, and
practices.
AB - BACKGROUND: The Whole School, Whole Community, Whole Child (WSCC) model provides
a framework for promoting greater alignment, integration, and collaboration
between health and education across the school setting and improving students'
cognitive, physical, social, and emotional development. By providing a learning
environment that ensures each student is emotionally and physically healthy,
safe, actively engaged, supported, and challenged, the WSCC model presents a
framework for school systems to evaluate, streamline, implement, and sustain
policies, processes, and practices. METHODS: This article examines the essential
roles of the school district and of schools in aligning, developing, and
implementing policy, processes, and practices to create optimal learning
environments that support the whole child. RESULTS: Three key factors advance
efforts to align policies, processes, and practices. These include hiring a
coordinator at the district and school levels, having collaborative teams address
health and learning at the district and school levels, and using data to make
decisions and build health outcomes into school and district accountability
systems. CONCLUSIONS: These key factors provide a road map for successfully
implementing WSCC. More research is needed to determine the extent that
coordinators, collaborative teams, and the inclusion of health indicators in
accountability systems impact student health and learning.
PMID- 26440822
TI - A whole school approach: collaborative development of school health policies,
processes, and practices.
AB - BACKGROUND: The Whole School, Whole Community, Whole Child (WSCC) model shows the
interrelationship between health and learning and the potential for improving
educational outcomes by improving health outcomes. However, current descriptions
do not explain how to implement the model. METHODS: The existing literature,
including scientific articles, programmatic guidance, and publications by
national agencies and organizations, was reviewed and synthesized to describe an
overview of interrelatedness of learning and health and the 10 components of the
WSCC model. RESULTS: The literature suggests potential benefits of applying the
WSCC model at the district and school level. But, the model lacks specific
guidance as to how this might be made actionable. A collaborative approach to
health and learning is suggested, including a 10-step systematic process to help
schools and districts develop an action plan for improving health and education
outcomes. Essential preliminary actions are suggested to minimize the impact of
the challenges that commonly derail systematic planning processes and program
implementation, such as lack of readiness, personnel shortages, insufficient
resources, and competing priorities. CONCLUSIONS: All new models require testing
and evidence to confirm their value. District and schools will need to test this
model and put plans into action to show that significant, substantial, and
sustainable health and academic outcomes can be achieved.
PMID- 26440823
TI - Building sustainable health and education partnerships: stories from local
communities.
AB - BACKGROUND: Growing health disparities have a negative impact on young people's
educational achievement. Community schools that involve deep relationships with
partners across multiple domains address these disparities by providing
opportunities and services that promote healthy development of young people, and
enable them to graduate from high school ready for college, technical school, on
the-job training, career, and citizenship. METHODS: Results from Milwaukie High
School, North Clackamas, OR; Oakland Unified School District, Oakland, CA; and
Cincinnati Community Learning Centers, Cincinnati, OH were based on a review of
local site documents, web-based information, interviews, and e-mail communication
with key local actors. RESULTS: The schools and districts with strong health
partnerships reflecting community schools strategy have shown improvements in
attendance, academic performance, and increased access to mental, dental, vision,
and health supports for their students. CONCLUSIONS: To build deep health
education partnerships and grow community schools, a working leadership and
management infrastructure must be in place that uses quality data, focuses on
results, and facilitates professional development across sectors. The leadership
infrastructure of community school initiatives offers a prototype on which others
can build. Moreover, as leaders build cross-sector relationships, a clear
definition of what scaling up means is essential for subsequent long-term
systemic change.
PMID- 26440824
TI - Using the Whole School, Whole Community, Whole Child model: implications for
practice.
AB - BACKGROUND: Schools, school districts, and communities seeking to implement the
Whole School, Whole Community, Whole Child (WSCC) model should carefully and
deliberately select planning, implementation, and evaluation strategies. METHODS:
In this article, we identify strategies, steps, and resources within each phase
that can be integrated into existing processes that help improve health outcomes
and academic achievement. Implementation practices may vary across districts
depending upon available resources and time commitments. RESULTS: Obtaining and
maintaining administrative support at the beginning of the planning phase is
imperative for identifying and implementing strategies and sustaining efforts to
improve student health and academic outcomes. Strategy selection hinges on
priority needs, community assets, and resources identified through the planning
process. Determining the results of implementing the WSCC is based upon a
comprehensive evaluation that begins during the planning phase. Evaluation guides
success in attaining goals and objectives, assesses strengths and weaknesses,
provides direction for program adjustment, revision, and future planning, and
informs stakeholders of the effect of WSCC, including the effect on academic
indicators. CONCLUSIONS: With careful planning, implementation, and evaluation
efforts, use of the WSCC model has the potential of focusing family, community,
and school education and health resources to increase the likelihood of better
health and academic success for students and improve school and community life in
the present and in the future.
PMID- 26440825
TI - Novel computer vision algorithm for the reliable analysis of organelle morphology
in whole cell 3D images--A pilot study for the quantitative evaluation of
mitochondrial fragmentation in amyotrophic lateral sclerosis.
AB - The function of intact organelles, whether mitochondria, Golgi apparatus or
endoplasmic reticulum (ER), relies on their proper morphological organization. It
is recognized that disturbances of organelle morphology are early events in
disease manifestation, but reliable and quantitative detection of organelle
morphology is difficult and time-consuming. Here we present a novel computer
vision algorithm for the assessment of organelle morphology in whole cell 3D
images. The algorithm allows the numerical and quantitative description of
organelle structures, including total number and length of segments, cell and
nucleus area/volume as well as novel texture parameters like lacunarity and
fractal dimension. Applying the algorithm we performed a pilot study in cultured
motor neurons from transgenic G93A hSOD1 mice, a model of human familial
amyotrophic lateral sclerosis. In the presence of the mutated SOD1 and upon
excitotoxic treatment with kainate we demonstrate a clear fragmentation of the
mitochondrial network, with an increase in the number of mitochondrial segments
and a reduction in the length of mitochondria. Histogram analyses show a reduced
number of tubular mitochondria and an increased number of small mitochondrial
segments. The computer vision algorithm for the evaluation of organelle
morphology allows an objective assessment of disease-related organelle phenotypes
with greatly reduced examiner bias and will aid the evaluation of novel
therapeutic strategies on a cellular level.
PMID- 26440827
TI - Rehabilitation lessons from the 2005 Pakistan earthquake and others since -
looking back and ahead?
PMID- 26440826
TI - GSK-3beta controls autophagy by modulating LKB1-AMPK pathway in prostate cancer
cells.
AB - BACKGROUND: Glycogen synthase kinase 3beta (GSK3B, GSK-3beta) is a multi
functional protein kinase involved in various cellular processes and its activity
elevates after serum deprivation. We have shown that inhibition of GSK-3beta
activity triggered a profound autophagic response and subsequent necrotic cell
death after serum deprivation in prostate cancer cells. In this study, we
dissected the mechanisms involved in GSK-3beta inhibition-triggered autophagy.
METHODS: Prostate cancer PC-3 and DU145 cells were used in the study. Multiple
GSK-3beta specific inhibitors were used including small chemicals TDZD8,
Tideglusib, TWS119, and peptide L803-mts. Western blot assay coupled with phospho
specific antibodies were used in detecting signal pathway activation. ATP levels
were assessed with ATPLite kit and HPLC methods. Autophagy response was
determined by evaluating Microtubule-associated proteins 1A/1B light chain 3B
(LC3B) processing and p62 protein stability in Western blot assays.
Immunofluorescent microscopy was used to detect LKB1 translocation. RESULTS:
Inhibition of GSK-3beta activity resulted in a significant decline of cellular
ATP production, leading to a significant increase of AMP/ATP ratio, a strong
trigger of AMP-activated protein kinase (AMPK) activation in prostate cancer PC-3
cells. In parallel with increased LC-3B biosynthesis and p62 protein reduction,
the classical sign of autophagy induction, AMPK was activated after inhibition of
GSK-3beta activity. Further analysis revealed that Liver kinase B1 (LKB1) but not
Calcium/calmodulin-dependent protein kinase kinase beta (CaMKKbeta) is involved
in AMPK activation and autophagy induction triggered by GSK-3beta inhibition.
Meanwhile, GSK-3beta inhibition promoted LKB1 translocation from nuclear to
cytoplasmic compartment and enhanced LKB1 interaction with its regulatory
partners Mouse protein-25 (MO25) and STE20-related adaptor (STRAD). CONCLUSIONS:
In conclusion, our data suggest that GSK-3beta plays an important role in
controlling autophagy induction by modulating the activation of LKB1-AMPK pathway
after serum deprivation.
PMID- 26440828
TI - Clinical practice guidelines and introduction of CME/CPD for all GPs and
specialist: A science of continuing medical education, should it be considered
mandatory?
PMID- 26440829
TI - The effect of home-based pulmonary rehabilitation on self-efficacy in chronic
obstructive pulmonary disease patients.
AB - OBJECTIVE: To investigate the effect of pulmonary rehabilitation on the self
efficacy of patients with chronic obstructive pulmonary disease. METHODS: The
randomised case-control trial was conducted from December 2010 to February 2011
at Masih-Daneshvari Hospital, Tehran, Iran, in an outpatient clinic and comprised
patients with mild to moderate chronic obstructive pulmonary disease. The
patients were randomly divided into experimental and control groups. The
pulmonary rehabilitation programme for the experimental group consisted of
education about the disease, diet therapy, stress reduction methods, effective
cough, breathing exercises, and muscle stretching exercises. The patients were
encouraged to practise the programme at home three times per week for 7 weeks.
They were followed up through weekly telephone contacts. The control group
received only routine visits and weekly telephone follow-up. Data were gathered
using the Persian version of chronic obstructive pulmonary disease self-efficacy
scale, which was filled out at baseline and 7 weeks post-intervention. SPSS 16
was used for statistical analysis. RESULTS: Of the 66 patients in the study,
34(51.5%) were in cases and 32(48.5%) were controls. The overall mean age was
56.65+/-8.83 years and 47(71.2%) were males. There was a significant difference
between the two groups in total score of self-efficacy (p<0.001) and so was the
case with all subscales of self-efficacy (p<0.001). CONCLUSIONS: Pulmonary
rehabilitation programme can be used by nurses during discharge planning for
patients in order to improve all subscales of self-efficacy of those suffering
from chronic obstructive pulmonary disease.
PMID- 26440830
TI - Premarital genetic screening for beta thalassemia carrier status of indexed
families using HbA2 electrophoresis.
AB - OBJECTIVE: To devise a strategy for prevention of beta thalassemia in newborns
through reliable screening of indexed families. METHODS: The cross-sectional
study was conducted over six months in 2011 and comprised blood samples collected
from subjects belonging to different ethnic groups from families of beta
thalassemia major children registered with the Abbottonian Medical Association
Blood Care Centre, Abbottabad, in Pakistan's Khyber Pakhtunkhwa province.
Electrophoretic separation of human haemoglobin like A, F, S and C was done and
then haemoglobin in the gel was immobilised in a fixative solution and the gel
was dried to a film. Haemoglobin pattern was visualised by staining the film with
a protein-specific stain. The pattern was quantified by densitometry. RESULTS: Of
the 98 samples, 57(58.2%) had b-thalassemia trait with elevated haemoglobin alpha
2 level, and 41(41.8%) had normal level. Out of the 57 carriers, 33(57.89%) were
males and 24(42.10%) were females. Mean age of carriers was 11.65+/-6.25 years
compared to 10.93+/-7.75 in normal patients. Mean haemoglobin alpha 2 level of
carriers was 5.2+/-0.56% compared to 2.34+/-0.57% in normal subjects.
CONCLUSIONS: Carrying out mass screening programmes throughout Pakistan for the
detection of thalassemia carriers and providing them the benefit of marriage
counselling may decrease the incidence of thalassemia Major.
PMID- 26440831
TI - Perceptions of undergraduate medical students regarding case based learning and
tutorial format.
AB - OBJECTIVE: To evaluate the perception of medical students regarding tutorial and
case-based learning formats. METHODS: The within stage mixed model research was
conducted at the Army Medical College, National University of Sciences and
Technology, Islamabad, Pakistan, from April 2012 to March 2013, and comprised
medical students of 4th year. Data-collection tool was a self-developed
questionnaire, and it was statistically analysed using SPSS 16. RESULTS: Of the
144 students, 86(60%) were males. The overall age range was 21.5-23.4 years. Case
based learning method had significantly higher scores compared to tutorial method
for learning process (p<0.001), for behavioural influence of facilitators
(p<0.001), for group dynamics (p<0.001), and for learning environment (p<0.001).
For open-ended questions regarding like or dislike of the two methods, majority
named some faculty members as their role models and appreciated their support in
better and in-depth learning through case-based learning format. CONCLUSIONS:
Case-based learning format was significantly more appreciated and favoured as a
learning strategy by students.
PMID- 26440832
TI - Frequency of corneal dystrophies on the basis of histopathology in surgically
removed corneas.
AB - OBJECTIVE: To assess the frequency of corneal dystrophies on the basis of
histopathology in surgically-removed corneas. METHODS: The descriptive study was
conducted at Foundation University Medical College, Islamabad, and Al Shifa Eye
Hospital, Rawalpindi, Pakistan, from May to October 2011, and comprised post
keratoplasty corneal specimen irrespective of age and gender. The surgically
removed corneas were processed according to the standard guidelines of
histopathological processing. The histopathological sections were examined for
various corneal dystrophies. Data was recorded on a proforma and was analysed
using SPSS 17. RESULTS: Of the 63 patients in the study, 12(19%) were diagnosed
as having corneal dystrophies. In these 12 patients, 6(50%)were diagnosed as
stromal corneal dystrophies and 5(42%)had posterior corneal dystrophies, and
1(8%)had anterior corneal dystrophy. CONCLUSIONS: Histopathological examination
of corneas is a reliable method to diagnose and classify corneal dystrophies.
PMID- 26440833
TI - Socio-demographic risk factors of mobility dysfunction and limitations in
physical functioning disability among the elderly in Iran: A nationwide cross
sectional survey.
AB - OBJECTIVE: To examine self-reported mobility and limitation in physical
functioning among the elderly and associated socio-demographic risk factors.
METHODS: The population-based cross-sectional study was conducted from January
2012 to January 2013 and comprised subjects from five provinces of Iran. The
variables were measured using a questionnaire. Self-reported mobility disability
and physical functioning disability were defined as having no problems in daily
activities and physical tasks. Logistic regression was used to calculate the odds
ratio for association of socio-demographic risk factors and outcomes. RESULTS: Of
the 1325 subjects, 636(48%) were men. The overall mean age was 69.14+/-7.37
years. Prevalence of mobility disability and limitation in physical functioning
was 401(63%) and 553(87%) in men, and 524(76%) and 641(93%) in women. There was a
significant association between mobility disability and family composition and
satisfaction with financial situation and housing tenure in both genders (p<0.05
each). Physical functioning had a significant relationship with family
composition, and satisfaction with financial situations and housing tenure in men
and women and population density in men and marital status in women (p<0.05
each). CONCLUSIONS: The elderly had a high risk of disability. Social factors had
more association with mobility disability and limitation in physical functioning
and required specific social support.
PMID- 26440834
TI - Short term outcome and predictors of response to neoadjuvant treatment in rectal
cancer.
AB - OBJECTIVE: To evaluate response to neoadjuvant chemoradiation in the treatment of
rectal cancer and to see if it can be predicted whether a particular patient will
benefit from such treatment. METHODS: The retrospective case series was done at
the Aga Khan University Hospital, Karachi, and comprised data related to period
from January 2005 to December 2014 of patients with rectal cancer who had
received neoadjuvant treatment. They were divided into responders and non
responders on the basis of imaging. Pre-treatment factors were compared to
identify differences in the two groups. SPSS 19 was used for statistical
analysis. RESULTS: The median age of 35 patients whose records were studied was
44 years (interquartile range: 33-54). Response to neoadjuvant treatment was seen
in 13(37%) patients with complete pathological response in 8(22.9%). There was no
statistically significant difference in age, gender, pre-treatment tumour stage,
tumour biology and distance from anal verge among the responders and the non
responders (p>0.05 each). CONCLUSIONS: Response to neoadjuvant treatment in
rectal cancer was low.
PMID- 26440835
TI - Challenges of providing timely feedback to residents: Faculty perspectives.
AB - OBJECTIVE: To explore faculty's perceptions of challenges in providing verbal
feedback to the Residents and suggest ways to overcome the barriers. METHODS: As
part of a larger study on feedback assessment, five focus group discussions were
conducted at the Department of Medicine, Aga Khan University Hospital, Karachi,
during faculty development workshops held from January to June 2010. Qualitative
grounded theory was used to explore faculty perceptions of challenges in
providing verbal feedback to the Residents. RESULTS: Of the 54 faculty members,
49(91%) participated. Four themes that emerged were 'time constraint' indicating
high patient load; 'faculty related issues' indicating faculty's apprehension
about its own evaluation by Residents; 'educational issues' indicating that the
importance of feedback was not emphasised; and 'system and logistic issues'
indicating that the assessment form used for assessing Residents was ambiguous.
CONCLUSIONS: Work load of the faculty and the expectations with respect to
patient care responsibilities may have an impact on the quality, timing, content
and delivery of the feedback provided to the Residents.
PMID- 26440836
TI - Knowledge, attitude and practices amongst the Pakistani females towards breast
cancer screening programme.
AB - OBJECTIVE: To assess the knowledge, attitude and practices amongst Pakistani
females towards breast screening programmes. METHODS: The descriptive cross
sectional study was conducted from June 2013 to July2014 at Mayo Hospital,
Lahore, and comprised attendants and patients who visited out-patients department
and/or were treated as in-patients. The questionnaire contained 25 open and close
ended questions regarding knowledge and attitude, along with 7 questions
regarding practices. Data was analysed using SPSS 17. RESULTS: There were 1184
women with a mean age of 32.7+/-8.6 years. The mean score was 12.7+/-4.9.
Positive family history of breast cancer was reported by 156(13.2%) women;
420(35.5%) believed advancing age was a risk factor; 1041(87.9%) never had breast
self-examination; 1106(93.4%) never had a clinical breast examination; and
1171(98.9%) never had screening mammogram. CONCLUSIONS: The knowledge and
practices regarding breast cancer screening, breast self-examination and
mammogram among women were not good. The knowledge about breast cancer risk
factors was very poor and showed an alarming attitude towards practices.
PMID- 26440837
TI - The effects of healthy lifestyle behaviors of mothers on obesity in preschool
children.
AB - OBJECTIVE: To determine the relationship between healthy lifestyle behaviours of
mothers and obesity in their pre-school children. METHODS: The cross-sectional
study was performed in a district of Istanbul, Turkey, between April and June
2011, and comprised children aged 4-6 years attending public pre-schools and
their mothers.. Data was obtained using a questionnaire and Healthy Lifestyle
Behaviours Scale-II. Number Cruncher Statistical System 2007 was used for
statistical analysis. RESULTS: Of the 531 children in the study, 246(46.3%) were
girls. Overall prevalence of overweight was 136(25.6%), obesity
77(14.5%)Overweight mothers were 126(23.7%), and obese mothers were 31(5.8%). The
mothers of obese children obtained lower scores in the physical activity (p<0.05)
and nutrition (p=0.001) subscales, and their total score was also lower
(p<0.05).. CONCLUSIONS: Lifestyle behaviours of mothers, especially with respect
to nutrition and physical activity, may influence obesity among preschool
children. Strategies should be developed to improve the physical activity and
eating habits of mothers.
PMID- 26440838
TI - Role of vitamin E in preventing arteriohyalinization in kidneys of streptozotocin
induced diabetic mice.
AB - OBJECTIVE: To evaluate the role of vitamin E on the arteriolar hyalinisation in
kidneys of diabetic mice. METHODS: The laboratory-based randomised control trial
was conducted at the Department of Anatomy, Army Medical College, Rawalpindi, in
collaboration with National Institute of Health, Islamabad, from November 2009 to
November 2010. Adult female BALB/C mice were randomly divided into three groups.
Group A served as control group. Group B was made diabetic by the intraperitoneal
injection of streptozotocin. Group C received streptozotocin injection and was
fed with vitamin E (alphatocopherol) supplemented diet. After 12 weeks,the
animals were sacrificed and their kidneys were removed for histomorphological
study. SPSS 16 was used for statistical analysis. RESULTS: Diabetes caused
significant histomorphological changes in arteriole of kidneys of Experimental
Group B compared to Control Group A (p>0.05), but these changes were prevented in
Group C. In experimental group B, 2(20%) animals had arteriolar hyalinisation of
score 1, while score 2 was revealed in 8(80%) animals. Experimental group C
showed no hyalinisation in any arteriole. CONCLUSIONS: Vitamin E prevents the
arteriohyalinization in kidneys of mice with STZ induced diabetes.
PMID- 26440839
TI - Root cause analysis of methicillin resistant Staphylococcus aureus bacteraemia.
AB - OBJECTIVE: To find the important risk factors and sources of bacteraemia in
patients suffering from methicillin-resistant staphylococcus aureus bacteraemia.
METHODS: The descriptive study was carried out at Shaikh Zayed Hospital, Lahore,
from October 2010 to August 2011. Blood cultures were processed to isolate
methicillin-resistant staphylococcus aureus. A questionnaire was completed by the
participating patients suffering from bacteraemia. Information about risk factors
present at the time and risk factors that served as the source of bacteraemia
were noted. RESULTS: Total 4058 blood cultures were processed and 669(16.5%) were
positive. Of them, 194(29%) cultures were found to be positive for staphylococci.
Out of these 194 blood cultures, coagulase-negative staphylococci were isolated
from 117(60%), and 77(40%) were positive for S. aureus. Out of these 77 samples,
26(34%) were found to be methicillin-sensitive staphylococcus aureus and 51(66%)
were methicillin-resistant staphylococcus aureus. The overall frequency of
methicillin-resistant staphylococcus aureus was 1.25%; 7.62% out of positive
blood culture; 26.28% out of total staphylococci; and 66% out of total S. aureus.
As for the source of infection, central venous pressure line 11(21.6%), post
influenza pneumonia 9(17.6%), peripheral intravenous line 8(15.7%) and dialysis
line 7(13.7%) were major reasons. CONCLUSIONS: Taking care of aseptic measures
while insertion, frequent change and early removal of the central venous and
dialysis lines is of critical significance.
PMID- 26440840
TI - Role of nicotine and camellia sinensis on the developing femur of chick.
AB - OBJECTIVE: To study the harmful effects of nicotine on the developing femur of
chick and to observe the role of antioxidant camellia sinensis in the prevention
of these effects. METHODS: The experimental study was conducted at Army Medical
College, Rawalpindi, from November 2, 2011, to November 1, 2012, and comprised
fresh fertilised eggs of Fayoumi species at zero hour of incubation of Fayoumi
species. The eggs were divided into four equal groups. Control group G1 was given
normal saline; G2 was given green tea extract; G3 was given 0.0001% nicotine
solution; and G4 was given both 0.0001% nicotine solution and green tea extract.
First exposure was at 48 hours of incubation and second at 48 hours of hatching
(post-natal dose).At the age of one month, the chicks were sacrifised. The length
of the femurs was measured with the help of measuring scale by keeping the ruler
between greater trochanter and the lateral condyle. SPSS 16 was used for
statistical analysis. RESULTS: The four groups had 10 eggs each. G3 and G4 showed
decreased growth compared to G1 and G2 (p<0.05). In G4, better growth was noticed
compared to G3 (p<0.05), but its growth was less in comparison with G1 and
G2(p>0.05). CONCLUSIONS: Camellia sinensis antioxidant property helped to
neutralise the oxidative injury by the use of nicotine, but was unable to recover
it fully.
PMID- 26440842
TI - Fresh garlic amelioration of high-fat-diet induced fatty liver in albino rats.
AB - OBJECTIVE: To observe the effect of fresh garlic on high-fat-diet-induced fatty
liver changes. METHODS: The experimental study was conducted at the Jinnah
Postgraduate Medical Centre, Karachi, from October to November 2008, and
comprised adult albino rats weighing 200-240g each. The rats were divided into 5
groups according to dietary regimen for eight weeks each. Group A received
control diet; Group B received high saturated fat diet; Group C received high
unsaturated fat diet; Group D received high saturated fat diet with fresh garlic;
and Group E received high unsaturated fat diet with garlic for 8 weeks. Liver
tissue slides were stained with Oil red-O and haematoxylin and Periodic acid
Schiff-haematoxylin. RESULTS: The 50 rats in the study were divided into five
groups of 10(20%) each. There was marked deposition of fat in hepatocyte along
with marked decrease in glycogen content in liver of rats in Groups B and C, with
Group B showing more marked changes. The changes in fat and glycogen content were
reversed and ameliorated close to Group A in rats belonging to Groups D and E.
CONCLUSIONS: Fresh garlic minimised the high-fat-diet-induced fatty liver changes
in rats.
PMID- 26440841
TI - Pregnancy of unknown location: Outcome in a tertiary care hospital.
AB - OBJECTIVE: To find out the outcome of a cohort of women with pregnancy of unknown
location presenting to a tertiary care hospital. METHODS: The prospective study
was conducted from January to December, 2011, at Early Pregnancy Assessment Unit,
King Faisal Military Hospital, Khamis Mushait, Saudi Arabia. Data was collected
for women with early pregnancy or with history of amenorrhoea, bleeding or pain.
These women were investigated with serum beta-human chorionic gonadotrophin
levels twice weekly and transvaginal ultrasonography weekly. Expectant management
was done for failing pregnancy of unknown location while medical or surgical
management was considered for persistent pregnancy of unknown location and
ectopic pregnancy. RESULTS: During study period, 7215 patients were admitted,
and, of them, 2212(30.6%) were patients with early pregnancy. Meeting the
inclusion criteria were 183(2.53%) patients who formed the study sample. There
were 131(71.6%) patients presenting with amenorrhoea, 90(49.2%) had bleeding and
93(50.8%) presented with pain. Outcome of 100(54.6%) patients was failing
pregnancy of unknown location, 58(31.7%) had intrauterine pregnancy, 14(7.7%)
converted to ectopic pregnancy, while 11(6%) had persistent pregnancy of unknown
location. All patients with persistent pregnancy of unknown location and 5(36%)
patients with ectopic pregnancy were medically treated. Five (36%) patients
having ectopic pregnancy were managed surgically. CONCLUSIONS: Management of
choice for asymptomatic patients having pregnancy of unknown location is
expectant management. Most of the patients suspected to have Most of the patients
with persistent pregnancy of unknown location and ectopic pregnancy can be
managed medically.
PMID- 26440843
TI - The awareness of experience innovation and an application in private hospitals.
AB - OBJECTIVE: To evaluate the perspective of private hospitals regarding experience
innovation. METHODS: The qualification-type study was conducted in Istanbul,
Turkey, in February 2015, and comprised 17 hospitals where patients and employees
were interviewed using a semi-structured consultation guide. The employees were
examined regarding the meaning of innovation, awareness of experience innovation
and its measurement. The patients were asked about the reason for choosing a
hospital, the actual reason for arrival at the hospital and the impressions while
leaving the hospital. Based on the obtained answers, experience innovation was
examined. RESULTS: Of the 87 subjects interviewed, 51(59%) were patients and
36(41%) were hospital employees. Overall, there were 61(70%) women and 26(30%)
men in the age range of 21-75 years. It was observed that the tendencies of
hospitals for innovation activities were high, but they confused it with novelty.
CONCLUSIONS: Investments made without taking experience innovation into account
do not convert into targeted results.
PMID- 26440844
TI - Saudi Arabia: A future regional hub for advanced education, research, science and
technology.
AB - Saudi Arabia is the largest country of the Arabian Peninsula, blessed with
significant natural resources, including oil, gas and minerals. Saudi Arabia has
recognised the importance of education in social and economic transformation, and
has established a large number of universities, research and advanced technical
institutes which have broken the metropolitan boundaries and have been extended
to the far-flung areas of the country. There are 68 universities and degree
awarding institutes. The educational budget reached its highest-ever level of
$56.56 billion for the year 2014. About 124,000 Saudi students are pursuing
higher education in about 500 universities around the world. Saudi Arabia
produced 177826 research papers in Institute for Scientific Information (ISI)
database and in the year 2014 alone, 26168 research papers were published in
indexed science journals with a rising h-index of 144. The country is turning
into a regional hub for advanced education, research, science and technology
while swiftly shifting from an oil-based to a knowledge-based economy.
PMID- 26440845
TI - Gender association of prayer for health - perspective from university students in
Islamabad and Rawalpindi.
AB - The role of religion and spirituality in coping with disease and promoting health
has been reported from many parts of the World. However, no scientific studies on
the use of prayers for health and wellbeing have been reported from Pakistan. A
cross-sectional survey, using a self-administered questionnaire, was conducted
among 1342 graduate and undergraduate students in the twin cities of Islamabad
and Rawalpindi. A huge majority of students had prayed for their own as well as
their family members' health in the preceding three months. There is a need to
better understand the role in Pakistan of prayers related to health.
PMID- 26440846
TI - A rare and unexpected case of retained foetal bone after an unsafe abortion.
AB - Unsafe abortion is one of the most neglected healthcare problems in developing
countries. One of the rare complications of unsafe abortion is retained foetal
bone. Prevalence of disease is around 0.15% among patients undergoing diagnostic
hysteroscopy. Patients have no specific symptoms. Case reports have focused on
subfertility, abnormal uterine bleeding, lower abdominal pain, abnormal vaginal
discharge, dyspareunia, dysmenorrhoea and spontaneous passage of bony fragments.
Retained foetal bone fragments may cause acute pelvic inflammatory disease in
rare cases regardless of the time interval after abortion. This condition can
also present as recurrent vagitinis or endometritis refractory to ampirical
antimicrobial treatment. In such cases, foreign body in uterine cavity should be
kept in mind. Such patients should primarily be evaluated by ultrasonography
which has substantial clinical importance in differential diagnosis of these
cases. We present a case of misdiagnosed retained foetal bone complicated with
recurrent vaginal discharge and acute pelvic inflammatory disease.
PMID- 26440847
TI - Cryptococcus neoformans and Streptococcus pneumoniae co-infection in post
traumatic meningitis in a patient with unknown HIV status.
AB - Meningitis is a serious disease associated with considerable morbidity and
mortality. Mixed meningeal infections due to bacteria and fungi are exceptionally
rare. Here we report a case of meningeal co-infection with cryptococcus
neoformans and streptococcus pneumoniae in a patient with unknown human
immunodeficiency virus status. Because of the rarity of such cases, stringent
screening of every cerebrospinal fluid specimen to exclude the presence of
multiple pathogens is imperative. Assessment of patients for immunodeficiencies
in case of isolation of an opportunistic organism like cryptococcus is also
needed.
PMID- 26440848
TI - Autoimmune pancreatitis with extraocular muscles involvement.
AB - Autoimmune pancreatitis is characterised by diffuse enlargement of pancreas,
narrowing of pancreatic duct, lymphoplasmacytic infiltrations and fibrosis. The
disease is responsive to corticosteroid. We report the case of a 32-year-old male
who presented with unilateral exophthalmos and obstructive jaundice secondary to
pancreatic head mass and biliary tract stricture. Serum immunoglobulin G level
was raised with a very high immunoglobulin G4 subclass. Ophthalmological imaging
revealed unilateral thickening of extraocular muscles. The patient responded well
to corticosteroid with resolution of biliary strictures, pancreatic head mass and
exophthalmos.
PMID- 26440849
TI - Hereditary Sensory Autonomic Neuropathy II, a rare disease in a large Pakistani
family.
AB - Hereditary Sensory Autonomic Neuropathy II (HSAN II) is a rare genetic disorder,
characterized by severe loss of pain, temperature and touch sensation. Injuries
in these patients can progress to necrosis and shedding of digits and limbs. Here
we report two cases of HSAN II belonging to a Pakistani family. Individual 1, a
forty five year old man, had complete loss of pain sensation since birth. Self
mutilation and complication of injuries resulted in the shedding of all the
digits and right foot and surgical amputation of left leg. Individual 2, a five
year old girl,had delay in healing of wounds and self-mutilation. Examination
showed a complete lack of pain sensation throughout her body and hyporeflexia. As
the genetic cause of HSAN II is unknown, identification of more patients will
allow further research on this disease and possibly develop a cure.
PMID- 26440850
TI - Isoniazid induced motor-dominant neuropathy.
AB - Isoniazid though a very effective treatment for tuberculosis can cause severe
motor-dominant neuropathy which can be reversible with pyridoxine
supplementation. A 45-year-old female diagnosed with psoas abscess, culture
positive for mycobacterium tuberculosis, was started on anti- tuberculous
treatment with four drugs, including isoniazid at a dose of 5 mg/kg/day. Three
months later she developed severe motor weakness of lower limbs with loss of
ankle and knee reflexes. She was treated with vitamin B6 injections and isoniazid
treatment was continued. Her motor weakness gradually improved in a few months,
but mild sensory impairment persisted even after two years. There is need for
vigilance regarding neurological effects of isoniazid in seemingly low-risk
individuals in whom development of symptoms should raise the suspicion about slow
acetylator status. Timely therapeutic intervention with high-dose vitamin B6 can
reduce the long-term morbidity associated with this easily reversible condition.
PMID- 26440851
TI - Breast feeding: preventive therapy for type 2 diabetes.
AB - Exclusive breastfeeding for six months, continued along with top feed up to the
age of 2 years and beyond, is strongly recommended by the World Health
Organization. Apart from the various benefits that it provides, breast feeding
may also serve to prevent the development of type 2 diabetes and metabolic
syndrome in mothers, and type 1 diabetes and overweight/ obesity in their
offspring. This review discusses the evidence related to breastfeeding and type 2
diabetes. It highlights pertinent aspects of breast feeding management, which can
help facilitate optimal use of this natural preventive intervention.
PMID- 26440852
TI - Psychiatric disorders in diabetes.
AB - Diabetes and psychiatric disorders share a bi-directional relationship, with both
affecting each other adversely. Just as achieving glycaemic control is important,
so is ensuring that the person enjoys a good quality of life. All individuals
with diabetes must be screened regularly for co-morbidity, especially depressive
and anxiety disorders. Multiple evidence based psychotropic pharmacological
interventions are available for management of these psychiatric disorders.
Additionally, non-pharmacological interventions play a key role in comprehensive
management of such patients.
PMID- 26440853
TI - Stepwise and simple guide to medical writing and research for beginners.
PMID- 26440854
TI - Life of medical professionals in Pakistan.
PMID- 26440855
TI - Effect of nutritional deficiency on the efficacy of the polio vaccines in
Pakistan.
PMID- 26440856
TI - Laparoscopic-assisted percutaneous endoscopic gastrostomy tube insertion in the
immediate post-partum period for head and neck cancer.
AB - Percutaneous endoscopic gastrostomy (PEG) tube placement serves as a well
tolerated and efficacious technique for long-term enteral access in patients with
medical conditions precluding oral food intake. The nutritional optimisation of
patients with oral cancer is mostly achieved via PEG tube placement. However,
certain special situations, such as pregnancy and the immediate post-partum
period, may render the placement of PEG tubes to be a challenge. A 28-year-old
pregnant female patient presented to us with the diagnosis of squamous cell
carcinoma of the tongue during her third trimester. Definitive surgical resection
was planned post-delivery along with simultaneous PEG tube placement. Immediately
following delivery via an elective Caesarean section, she successfully underwent
laparoscopic-assisted PEG tube placement. A gravid uterus or an immediately post
partum distended uterus poses significant difficulties whilst attempting PEG
insertion. However, laparoscopic-assisted PEG insertion in a controlled setting
may make the process safer to perform.
PMID- 26440857
TI - Ethnobotanical study of medicinal plants used by traditional healers in Mascara
(North West of Algeria).
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are considered as a rich source
of bioactive compounds. The present study aimed to document the local knowledge
of medicinal plants' use by traditional healers in Mascara, North-west Algeria.
MATERIALS AND METHODS: The present study was carried out in Mascara (North West
of Algeria). Ethnobotanical data were recorded from 43 traditional healers
practicing in Mascara. Data collected was analysed using quantitative indices
such as the use value (UV), fidelity level (FL) and Informant Consensus Factor
(FIC). RESULTS: Traditional healers reported 141 medicinal plant species
belonging to 54 families and 125 genera for the treatment of different ailments
grouped into 14 ailments categories. Lamiaceae were the most represented family
with 19 species (13.57%) followed by Asteracea, Apiaceae and Fabaceae. Thymus
vulgaris L. was the most frequently used by local informants, with the highest UV
of 0.883 (38 use reports). Our findings revealed that 39 species have not been
previously reported as medicinal plants in the region. Furthermore, we report for
the first time a total of 100 new therapeutic uses for 37 known plant species.
FIC values ranged from 0.125 to 0.658. Gastro-intestinal diseases had the highest
FIC (0.658) with 60 species and 261 use reports. CONCLUSION: The present study
revealed the important local knowledge as showed by the variety of species used
to treat several ailments. Recorded species with high UV should be subjects of
further pharmacological studies to validate their popular use and to isolate the
bioactive compounds.
PMID- 26440858
TI - Development and comparison of a generic multiple-locus variable-number tandem
repeat analysis with pulsed-field gel electrophoresis for typing of Salmonella
enterica subsp. enterica.
AB - AIMS: Salmonella enterica subsp. enterica causes salmonellosis in humans and
animals. Serovar-specific multiple-locus variable-number tandem repeat analysis
(MLVA) is widely used for Salmonella surveillance; however, isolates have to be
serotyped prior to MLVA typing and only the most common serovars can be typed. We
developed a MLVA scheme for high-discriminatory typing of Salmonella. METHODS AND
RESULTS: Sixty-six unique VNTRs were investigated and the polymorphisms of seven
promising VNTRs were evaluated with a panel 163 diverse isolates of 14 serotypes
of significance for human health. Five VNTRs were selected for MLVA analysis. The
discriminatory power was evaluated within serovars by 163 isolates and MLVA
yielded 79 genotypes (DI of 0.9790) and pulsed-field gel electrophoresis (PFGE)
revealed 87 genotypes (DI of 0.9989). MLVA divided each serotype into 2-8
different profiles and identified six pairs of outbreak-related strains.
CONCLUSIONS: The technique showed a high-discriminatory power within most
serotypes comparable with or better than that of PFGE. SIGNIFICANCE AND IMPACT OF
THE STUDY: This MLVA assay makes it possible to use a single typing method for
Salmonella surveillance and outbreak investigations. This allows inexpensive and
fast surveillance for laboratories without resources for both serotyping and
molecular typing, e.g. PFGE or sequence-based methods, and thereby improve the
effectiveness of epidemiological investigations of Salmonella infections
globally.
PMID- 26440859
TI - Mesenchymal stromal SB623 cell implantation mitigates nigrostriatal dopaminergic
damage in a mouse model of Parkinson's disease.
AB - Regenerative medicine for the treatment of motor features in Parkinson's disease
(PD) is a promising therapeutic option. Donor cells can simultaneously address
multiple pathological mechanisms while responding to the needs of the host
tissue. Previous studies have demonstrated that mesenchymal stromal cells (MSCs)
promote recovery using various animal models of PD. SanBio Inc. has developed a
novel cell type designated SB623, which are adult bone marrow-derived MSCs
transfected with Notch intracellular domain. In this preclinical study, SB623
cells protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
induced nigrostriatal injury when transplanted unilaterally into C57BL/6 mouse
striatum 3 days prior to toxin exposure. Specifically, mice with the SB623 cell
transplants revealed significantly higher levels of striatal dopamine, tyrosine
hydroxylase immunoreactivity and stereological nigral cell counts in the
ipsilateral hemisphere vs vehicle-treated mice following MPTP administration.
Interestingly, improvement in markers of striatal dopaminergic integrity was also
noted in the contralateral hemisphere. These data indicate that MSCs
transplantation, specifically SB623 cells, may represent a novel therapeutic
option to ameliorate damage related to PD, not only at the level of striatal
terminals (i.e. the site of implantation) but also at the level of the nigral
cell body. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26440860
TI - Investigation of binding mechanism of novel 8-substituted coumarin derivatives
with human serum albumin and alpha-1-glycoprotein.
AB - Coumarin molecules have biological activities possessing lipid-controlling
activity, anti-hepatitis C activity, anti-diabetic, anti-Parkinson activity, and
anti-cancer activity. Here, we have presented an inclusive study on the
interaction of 8-substituted-7-hydroxy coumarin derivatives (Umb-1/Umb-2) with
alpha-1-glycoprotein (AGP) and human serum albumin (HSA) which are the major
carrier proteins in the human blood plasma. Binding constants obtained from
fluorescence emission data were found to be KUmb-1=3.1 +/- .01 * 10(4) M(-1),
KUmb-2 = 7 +/- .01 * 10(4) M(-1), which corresponds to -6.1 and -6.5 kcal/mol of
free energy for Umb-1 and Umb-2, respectively, suggesting that these derivatives
bind strongly to HSA. Also these molecules bind to AGP with binding constants of
KUmb-1-AGP=3.1 +/- .01 * 10(3) M(-1) and KUmb-2-AGP = 4.6 +/- .01 * 10(3) M(-1).
Further, the distance, r between the donor (HSA) and acceptor (Umb-1/Umb-2) was
calculated based on the Forster's theory of non-radiation energy transfer and the
values were observed to be 1.14 and 1.29 nm in Umb-1-HSA and Umb-2-HSA system,
respectively. The protein secondary structure of HSA was partially unfolded upon
binding of Umb-1 and Umb-2. Furthermore, site displacement experiments with
lidocaine, phenylbutazone (IIA), and ibuprofen (IIIA) proves that Umb derivatives
significantly bind to subdomain IIIA of HSA which is further supported by docking
studies. Furthermore, Umb-1 binds to LYS402 with one hydrogen bond distance of
2.8 A and Umb-2 binds to GLU354 with one hydrogen bond at a distance of 2.0 A.
Moreover, these molecules are stabilized by hydrophobic interactions and hydrogen
bond between the hydroxyl groups of carbon-3 of coumarin derivatives.
PMID- 26440861
TI - Metabolically healthy obese individuals: Key protective factors.
AB - OBJECTIVES: Obesity is a significant quality of life-impairing health problem
affecting industrialized nations. However, despite carrying a large fat mass,
some very obese individuals exhibit normal metabolic profiles (metabolically
healthy obesity). The physiological factors underlying their protective and
favorable metabolic profiles remain poorly defined. METHODS: A search of the
National Library of Medicine PubMed database was performed using the following
keywords: Metabolically healthy obese, metabolically normal obese, insulin
resistance, metabolically unhealthy normal weight, and uncomplicated obesity.
RESULTS: This article reviewed factors associated with severe obesity that lacks
complications, and suggests putative activities by which these obese individuals
avoid developing the clinical features of metabolic syndrome, or the metabolic
complications associated with severe obesity. CONCLUSIONS: Despite the knowledge
that visceral fat deposition is the seminal factor that ultimately causes insulin
resistance (IR) and the detrimental inflammatory and hormonal profile that
contributes to increase risk for cardiovascular disease, it remains unknown
whether metabolically healthy obesity (MHO) has genetic predisposing factors, and
whether MHO ultimately succumbs to IR and the metabolic syndrome, indicating a
need for prophylatic bariatric surgery.
PMID- 26440862
TI - An empirical method to determine inadequacy of dietary water.
AB - OBJECTIVES: The physiological regulation of total body water and fluid
concentrations is complex and dynamic. The human daily water requirement varies
because of differences in body size, dietary solute load, exercise, and
activities. Although chronically concentrated urine increases the risk of renal
diseases, an empirical method to determine inadequate daily water consumption has
not been described for any demographic group; instead, statistical analyses are
applied to estimate nutritional guidelines (i.e., adequate intake). This
investigation describes a novel empirical method to determine the 24-h total
fluid intake (TFI; TFI = water + beverages + moisture in food) and 24-h urine
volume, which correspond to inadequate 24-h water intake (defined as urine
osmolality of 800 mOsm/kg; U800). METHODS: Healthy young women (mean +/- standard
deviation; age, 20 +/- 2 y, mass, 60.8 +/- 11.7 kg; n = 28) were observed for 7
consecutive days. A 24-h urine sample was analyzed for volume and osmolality.
Diet records were analyzed to determine 24-h TFI. RESULTS: For these 28 healthy
young women, the U800 corresponded to a TFI >=2.4 L/d (>=39 mL/kg/d) and a urine
volume >=1.3 L/d. CONCLUSIONS: The U800 method could be employed to empirically
determine 24-h TFI and 24-h urine volumes that correspond to inadequate water
intake in diverse demographic groups, residents of specific geographic regions,
and individuals who consume specialized diets or experience large daily water
turnover. Because laboratory expertise and instrumentation are required, this
technique provides greatest value in research and clinical settings.
PMID- 26440863
TI - Enzyme Substrate Specificity Conferred by Distinct Conformational Pathways.
AB - Substrate recognition is one of the hallmarks of enzyme catalysis. Enzyme
conformational changes have been linked to selectivity between substrates with
little direct evidence. Aldolase, a glycolytic enzyme, must distinguish between
two physiologically important substrates, fructose 1-phosphate and fructose 1,6
bisphosphate, and provides an excellent model system for the study of this
question. Previous work has shown that isozyme specific residues (ISRs) distant
from the active site are responsible for kinetic distinction between these
substrates. Notably, most of the ISRs reside in a cluster of five surface alpha
helices, and the carboxyl-terminal region (CTR), and cooperative interactions
among these helices have been demonstrated. To test the hypothesis that
conformational changes are at the root of these changes, single surface-cysteine
variants were created with the cysteine located on helices of the cluster and
CTR. This allowed for site-specific labeling with an environmentally sensitive
fluorophore, and subsequent monitoring of conformational changes by fluorescence
emission spectrophotometry. These labeled variants revealed different spectra in
the presence of saturating amounts of each substrate, which suggested the
occurrence of different conformations. Emission spectra collected at various
substrate concentrations showed a concentration dependence of the fluorescence
spectra, consistent with binding events. Lastly, stopped-flow fluorescence
spectrophotometry showed that the rate of these fluorescence changes was on the
same time-scale as catalysis, thus suggesting a link between the different
fluorescence changes and events during catalysis. On the basis of these results,
we propose that different conformational changes may be a common mechanism for
dictating substrate specificity in other enzymes with multiple substrates.
PMID- 26440864
TI - Comparing the fixational and functional preferred retinal location in a pointing
task.
AB - Patients with central vision loss (CVL) typically adopt eccentric viewing
strategies using a preferred retinal locus (PRL) in peripheral retina.
Clinically, the PRL is defined monocularly as the area of peripheral retina used
to fixate small stimuli. It is not clear if this fixational PRL describes the
same portion of peripheral retina used during dynamic binocular eye-hand
coordination tasks. We studied this question with four participants each with a
unique CVL history. Using a scanning laser ophthalmoscope, we measured
participants' monocular visual fields and the location and stability of their
fixational PRLs. Participants' monocular and binocular visual fields were also
evaluated using a computer monitor and eye tracker. Lastly, eye-hand coordination
was tested over several trials where participants pointed to and touched a small
target on a touchscreen monitor. Trials were blocked and carried out monocularly
and binocularly, with a target appearing at 5 degrees or 15 degrees from screen
center, in one of 8 locations. During pointing, our participants often exhibited
long movement durations, an increased number of eye movements and impaired
accuracy, especially in monocular conditions. However, these compensatory changes
in behavior did not consistently worsen when loci beyond the fixational PRL were
used. While fixational PRL size, location and fixation stability provide a
necessary description of behavior, they are not sufficient to capture the
pointing PRL used in this task. Generally, patients use a larger portion of
peripheral retina than one might expect from measures of the fixational PRL
alone, when pointing to a salient target without time constraints. While the
fixational and pointing PRLs often overlap, the fixational PRL does not predict
the large area of peripheral retina that can be used.
PMID- 26440866
TI - Improvement in All-Cause Mortality With Blood Pressure Control in a Group of US
Veterans With Drug-Resistant Hypertension.
AB - The current definition of drug-resistant hypertension includes patients with
uncontrolled (URH) (taking >=3 antihypertensive medications) and controlled
hypertension (CRH; blood pressure [BP] <=140/90 mm Hg) (taking >=4 medications).
The authors hypothesized that all-cause mortality is reduced when URH is
controlled. Qualified patients followed at the Washington DC VA Medical Center
were included. BPs were averaged for each year of follow-up. In 2006, among 2906
patients who met the criteria for drug-resistant hypertension, 628 had URH.
During follow-up, 234 patients were controlled (group 1) and 394 patients
remained uncontrolled (group 2). The mortality rate among patients with URH was
28% (110 of 394) and among patients with CRH was 13% (30 of 234), a 54% reduction
(P<.01). Multivariate analysis identified independent predictors of mortality as
uncontrolled HTN (hazard ratio, 2.5; 95% confidence interval, 1.67-3.75; P<.01),
age (hazard ratio, 1.03; 95% confidence interval, 1.01-1.04; P<.01), and diabetes
(hazard ratio, 1.46; 95% confidence interval, 1.04-2.05; P<.027). The authors
conclude that controlling drug-resistant hypertension markedly reduces all-cause
mortality.
PMID- 26440865
TI - Perceptual organization, visual attention, and objecthood.
AB - We have previously demonstrated that the mere organization of some elements in
the visual field into an object attracts attention automatically. Here, we
explored three different aspects of this automatic attentional capture: (a) Does
the attentional capture by an object involve a spatial component? (b) Which
Gestalt organization factors suffice for an object to capture attention? (c) Does
the strength of organization affect the object's ability to capture attention?
Participants viewed multi-elements displays and either identified the color of
one element or responded to a Vernier target. On some trials, a subset of the
elements grouped by Gestalt factors into an object that was irrelevant to the
task and not predictive of the target. An object effect - faster performance for
targets within the object than for targets outside the object - was found even
when the target appeared after the object offset, and was sensitive to target
object distance, suggesting that the capture of attention by an object is
accompanied by a deployment of attention to the object location. Object effects
of similar magnitude were found for objects grouped by a combination of factors
(collinearity, closure, and symmetry, or closure and symmetry) or by a single
factor when it was collinearity, but not symmetry, suggesting that collinearity,
or closure combined with symmetry, suffices for automatic capture of attention by
an object, but symmetry does not. Finally, the strength of grouping in modal
completion, manipulated by varying contrast polarity between and within elements,
affected the effectiveness of the attentional capture by the induced object.
PMID- 26440867
TI - Complexities emanating from legalization of marijuana.
PMID- 26440868
TI - Moral decision-making among assertive community treatment (ACT) case managers: a
focus group study.
AB - The context of care in assertive community treatment (ACT) can be precarious and
generate ethical issues involving the principles of autonomy and paternalism.
This focus group study examined case managers' situated accounts of moral
reasoning. Our findings show how they expressed strong moral obligation towards
helping the clients. Their moral reasoning reflected a paternalistic position
where, on different occasions, the potential benefits of their interventions
would be prioritised at the expense of protecting the clients' personal autonomy.
The case managers' reasoning emphasised situational awareness, but there was a
risk of supporting paternalistic interventions and denying the clients' right to
autonomy.
PMID- 26440869
TI - Exploring sexual risks in a forensic mental health hospital: perspectives from
patients and nurses.
AB - Patients utilising forensic mental health inpatient services experience a range
of sexual risks, including vulnerability to sexual exploitation and exposure to
sexually transmissible infections. However, there is a paucity of research
exploring the issue of sexual risks from the standpoint of patients and the
nurses who work closely with them in inpatient secure settings. This article
presents findings from a qualitative exploratory study, which investigated the
views of patients and nurses about sexual relationships in forensic mental health
settings. Risk was a major theme arising from the data and is the focus of this
article. Subthemes from nurse participants included sexual safety, sexual
vulnerability, unplanned pregnancies, and male sexuality issues. Subthemes from
patients included risks associated with sexual activity, access to information
and sexual health care, unplanned pregnancies, vulnerability, and male sexuality
issues. Knowledge about these sexual risks by patients and nurses were well
articulated, however information and assistance were considered by patients to be
less than satisfactory in improving their knowledge or in providing the support
they considered important to reduce sexual risks. The issue of risk needs to be
addressed, and nurses would be well placed to contribute; however they require
education to improve their ability to provide sexual health education to patients
along with strategies to ensure patients receive the support and services they
require to reduce their exposure to sexual risks.
PMID- 26440870
TI - Medical emergency team response processes for behavioral health inpatient units:
implications for nursing education.
AB - Following a literature review of nurses' attitudes and perceived barriers
regarding the utilization of medical emergency teams (METs) and completing key
informant interviews with psychiatric nurses, a questionnaire developed by the
researcher was administered to inpatient psychiatric nurses to further examine
their attitudes and perceived barriers about MET utilization. Using a 23-item
questionnaire, the psychiatric nurses were asked to rate each item using a 5
point Likert scale. Results indicated that nurses did not have a clear
understanding of the criteria for calling a MET and also tended to seek out other
staff personnel and/or a physician consultation prior to initiating a MET call.
Results of this descriptive, quality improvement project were then used to revise
and refine nursing education and practice regarding MET utilization.
PMID- 26440871
TI - Unmet physical and mental healthcare needs among stimulant-using gay and bisexual
homeless men.
AB - The aim of this study was to gain a greater understanding of predictors of the
unmet physical and mental healthcare needs of homeless, stimulant-using, gay and
bisexual (G/B) men. This study correlated baseline self-reported unmet physical
and mental healthcare needs among stimulant-using homeless G/B men (n = 422, 18
46 years of age). A structured questionnaire was administered at baseline and
data were collected from October 2009 to January 2013. The study was approved by
the University of California Human Subjects' Protection committee and the Friends
Research Institute Human Research Protection Committee. Logistic regression
revealed that those who self-reported ever being married, being in fair or poor
health and in moderate-to-very severe pain, were more likely to experience unmet
needs for physical health care. In terms of unmet mental health needs, those who
self-reported moderate-to-very severe pain and/or those reporting having sex
while high, were more likely to report unmet needs for mental health care. In
contrast, those reporting receiving social support from others were less likely
to have an unmet mental healthcare need. Research implications are discussed as
they relate to access to healthcare needs among this vulnerable population.
PMID- 26440872
TI - Apathy: who cares? A concept analysis.
AB - Apathy has been identified as an independent clinical syndrome. As prevalent and
problematic as it is in the field of neuropsychiatry, there is no fully accepted
definition of apathy. In this study, a concept analysis utilizing Rodgers'
evolutionary approach was performed. CINAHL Plus with Full Text was searched, and
altogether 36 publications were identified for the concept analysis. Our study
shows that psychometric scales may have resulted in an inappropriate diagnosis of
depression instead of apathy. As a whole, the literature showed that apathy was
defined in comparison to depression as well as altered motivation, emotionality,
activity, interest, and initiative. We discuss the advances in the development of
apathy as an evolutionary concept. Consistent with Rodgers' evolutionary method,
these findings are not an endpoint.
PMID- 26440873
TI - A synthesis of the literature on trauma-informed care.
AB - Patients with a history of traumatic life events can become distressed or re
traumatized as the result of healthcare experiences. These patients can benefit
from trauma-informed care that is sensitive to their unique needs. However,
despite the widespread prevalence of traumatic life experiences such as sexual
assault and intimate partner violence, trauma-informed care has not been widely
researched or implemented. The purpose of this synthesis of the literature is to
examine existing research on trauma-informed care for survivors of physical and
sexual abuse. The following themes are discussed: trauma screening and patient
disclosure, provider-patient relationships, minimizing distress and maximizing
autonomy, multidisciplinary collaboration and referrals, and trauma-informed care
in diverse settings. This synthesis also explores implications for trauma
informed care research, practice and policy. The themes identified here could be
used as a framework for creating provider and survivor educational interventions
and for implementing trauma-informed care across disciplines. The findings of
this synthesis support further research on patient and provider experiences of
trauma-informed care, and research to test the efficacy of trauma-informed care
interventions across healthcare settings. Universal implementation of trauma
informed care can ensure that the unique needs of trauma survivors as patients
are met, and mitigate barriers to care and health disparities experienced by this
vulnerable population.
PMID- 26440875
TI - The leadership role of nurse educators in mental health nursing.
AB - Leadership behaviors and actions influence others to act, and leadership in
clinical practice is an important mediator influencing patient outcomes and staff
satisfaction. Indeed, positive clinical leadership has been positioned as a
crucial element for transformation of health care services and has led to the
development of the Practice Doctorate Movement in the United States. Nurse
educators in health care have a vital leadership role as clinical experts, role
models, mentors, change agents, and supporters of quality projects. By enacting
these leadership attributes, nurse educators ensure a skilled and confident
workforce that is focused on optimizing opportunities for students and graduates
to integrate theory and practice in the workplace as well as developing more
holistic models of care for the consumer. Nurse educators need to be active in
supporting staff and students in health care environments and be visible leaders
who can drive policy and practice changes and engage in professional forums,
research, and scholarship. Although nurse educators have always been a feature of
the nursing workplace, there is a paucity of literature on the role of nurse
educators as clinical leaders. This discursive article describes the role and
attributes of nurse educators with a focus on their role as leaders in mental
health nursing. We argue that embracing the leadership role is fundamental to
nurse educators and to influencing consumer-focused care in mental health. We
also make recommendations for developing the leadership role of nurse educators
and provide considerations for further research such as examining the impact of
clinical leaders on client, staff, and organizational outcomes.
PMID- 26440874
TI - Whose stress is making me sick? Network-stress and emotional distress in African
American women.
AB - Research on stress-related health outcomes in African-American women often
neglects "network-stress": stress related to events that occur to family,
friends, or loved ones. Data from the African-American Women's Well-Being Study
were analyzed to examine self-stress and network-stress for occurrence, perceived
stressfulness, and association with symptoms of psychological distress. Women
reported a higher number of network-stress events compared with self-stress
events. Occurrences of network-stress were perceived as undesirable and
bothersome as self-stress. Both types of stress were significantly associated
with psychological distress symptoms. Including network-stress may provide a more
complete picture of the stress experiences of African-American women.
PMID- 26440876
TI - The factor structure of the internet addiction tool with university students in
Jordan.
AB - Internet addiction is a growing phenomenon affecting people in varying ways
around the globe. This study examined the factor structure and internal
reliability of the Internet Addiction Test (IAT) with a heterogeneous sample of
university students in Jordan. The study used a cross-sectional design, and all
the questionnaires were completed in classrooms. A sample of 587 students from
seven universities in Jordan was obtained. The exploratory and confirmatory
factor analyses of the 20-item IAT revealed that a four-factor solution offered
the most parsimonious explanation of the data. The IAT reliably assesses distinct
domains of Internet addiction. These domains are Excessive Use, Loss/Suffer,
Attached To, and Impaired Social Relations. Thus, it is recommended to use the
obtained four factors when assessing Internet addiction among a similar
population.
PMID- 26440877
TI - Expressions of happiness.
PMID- 26440878
TI - "Keeping the peace": relevance of the concept for mental health nursing.
PMID- 26440879
TI - Pharmacotherapy as prophylactic treatment of post-traumatic stress disorder: a
review of the literature.
AB - Post-traumatic stress disorder has a lifetime prevalence of almost 9% in the
United States. The diagnosis is associated with increased rates of comorbid
substance abuse and increased rates of depression. Providers are taught how to
diagnose and treat PTSD, but little discussion is devoted to how to prevent the
disorder. Behavioral research in animal studies has provided some evidence for
the use of medications in decreasing the fear response and the reconsolidation of
memories. A heightened fear response and the re-experience of traumatic memory
are key components for diagnosis. The purpose of this literature review is to
examine the evidence for pharmacotherapy as prophylactic treatment in acute
stress/trauma in order to prevent the development of post-traumatic stress
disorder. The body of the review includes discussions on medications, medications
as adjunct to script-driven imagery, and special considerations for military,
first responders, and women. This article concludes with implications for
practice and recommendations for future research. The key words used for the
literature search were "prophylactic treatment of PTSD," "pharmacotherapy and
trauma," "pharmacological prevention of PTSD," "beta blockers and the prevention
of PTSD," "acute stress and prevention of PTSD," "propranolol and PTSD,"
"secondary prevention of PTSD," and "medications used to prevent PTSD." Findings
were categorized by medications and medications as adjunct to script-driven
imagery. The literature suggests that hydrocortisone, propranolol, and morphine
may decrease symptoms and diagnosis of post-traumatic stress disorder.
PMID- 26440881
TI - Classical and non-classical metabolic transformation of vitamin D in dermal
fibroblasts.
PMID- 26440882
TI - Structural and Functional Evidence for Testosterone Activation of GPRC6A in
Peripheral Tissues.
AB - G protein-coupled receptor (GPCR) family C group 6 member A (GPRC6A) is a
multiligand GPCR that is activated by cations, L-amino acids, and osteocalcin.
GPRC6A plays an important role in the regulation of testosterone (T) production
and energy metabolism in mice. T has rapid, transcription-independent
(nongenomic) effects that are mediated by a putative GPCR. We previously found
that T can activate GPRC6A in vitro, but the possibility that T is a ligand for
GPRC6A remains controversial. Here, we demonstrate direct T binding to GPRC6A and
construct computational structural models of GPRC6A that are used to identify
potential binding poses of T. Mutations of the predicted binding site residues
were experimentally found to block T activation of GPRC6A, in agreement with the
modeling. Using Gpr6ca(-/-) mice, we confirmed that loss of GPRC6A resulted in
loss of T rapid signaling responses and elucidated several biological functions
regulated by GPRC6A-dependent T rapid signaling, including T stimulation of
insulin secretion in pancreatic islets and enzyme expression involved in the
biosynthesis of T in Leydig cells. Finally, we identified a stereo-specific
effect of an R-isomer of a selective androgen receptor modulator that is
predicted to bind to and shown to activate GPRC6A but not androgen receptor.
Together, our data show that GPRC6A directly mediates the rapid signaling
response to T and uncovers previously unrecognized endocrine networks.
PMID- 26440883
TI - The Membrane Mimetic Affects the Spatial Structure and Mobility of EGFR
Transmembrane and Juxtamembrane Domains.
AB - The epidermal growth factor receptor (EGFR) is one of the most extensively
studied receptor tyrosine kinases, as it is involved in a wide range of cellular
processes and severe diseases. Recent works reveal that the single-helix
transmembrane domains and cytoplasmic juxtamembrane regions play an important
role in the receptor activation process. Here we present the results of our
investigation of the spatial structure and mobility of the EGFR transmembrane
domain and juxtamembrane regions in various membranelike environments, which shed
light on the effects of the membrane physical properties and composition on the
behavior of the juxtamembrane domain.
PMID- 26440884
TI - PKA Phosphorylation of NCLX Reverses Mitochondrial Calcium Overload and
Depolarization, Promoting Survival of PINK1-Deficient Dopaminergic Neurons.
AB - Mitochondrial Ca(2+) overload is a critical, preceding event in neuronal damage
encountered during neurodegenerative and ischemic insults. We found that loss of
PTEN-induced putative kinase 1 (PINK1) function, implicated in Parkinson disease,
inhibits the mitochondrial Na(+)/Ca(2+) exchanger (NCLX), leading to impaired
mitochondrial Ca(2+) extrusion. NCLX activity was, however, fully rescued by
activation of the protein kinase A (PKA) pathway. We further show that PKA
rescues NCLX activity by phosphorylating serine 258, a putative regulatory NCLX
site. Remarkably, a constitutively active phosphomimetic mutant of NCLX
(NCLX(S258D)) prevents mitochondrial Ca(2+) overload and mitochondrial
depolarization in PINK1 knockout neurons, thereby enhancing neuronal survival.
Our results identify an mitochondrial Ca(2+) transport regulatory pathway that
protects against mitochondrial Ca(2+) overload. Because mitochondrial Ca(2+)
dyshomeostasis is a prominent feature of multiple disorders, the link between
NCLX and PKA may offer a therapeutic target.
PMID- 26440885
TI - Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription
Factor Sugarbabe.
AB - The ChREBP/Mondo-Mlx transcription factors are activated by sugars and are
essential for sugar tolerance. They promote the conversion of sugars to lipids,
but beyond this, their physiological roles are insufficiently understood. Here,
we demonstrate that in an organism-wide setting in Drosophila, Mondo-Mlx controls
the majority of sugar-regulated genes involved in nutrient digestion and
transport as well as carbohydrate, amino acid, and lipid metabolism. Furthermore,
human orthologs of the Mondo-Mlx targets display enrichment among gene variants
associated with high circulating triglycerides. In addition to direct regulation
of metabolic genes, Mondo-Mlx maintains metabolic homeostasis through downstream
effectors, including the Activin ligand Dawdle and the Gli-similar transcription
factor Sugarbabe. Sugarbabe controls a subset of Mondo-Mlx-dependent processes,
including de novo lipogenesis and fatty acid desaturation. In sum, Mondo-Mlx is a
master regulator of other sugar-responsive pathways essential for adaptation to a
high-sugar diet.
PMID- 26440886
TI - An Aminopeptidase in the Drosophila Testicular Niche Acts in Germline Stem Cell
Maintenance and Spermatogonial Dedifferentiation.
AB - Extrinsic cues from the niche are known to regulate adult stem cell self-renewal
versus differentiation. Here, we report that an aminopeptidase Slamdance (Sda)
acts in the Drosophila testicular niche to maintain germline stem cells (GSCs)
and regulate progenitor germ cell dedifferentiation. Mutations in sda lead to
dramatic testicular niche deterioration and stem cell loss. Recombinant Sda has
specific aminopeptidase activity in vitro, and the in vivo function of Sda
requires an intact aminopeptidase domain. Sda is required for accumulation of
mature DE-cadherin, and overexpression of DE-cadherin rescues most sda mutant
phenotypes, suggesting that DE-cadherin is an important target of Sda. Finally,
Sda is both necessary and sufficient to promote dedifferentiation during aging
and recovery from genetically manipulated depletion of GSCs. Together, our
results suggest that a niche factor promotes both stem cell maintenance and
progenitor cell dedifferentiation.
PMID- 26440887
TI - ASIC3 Mediates Itch Sensation in Response to Coincident Stimulation by Acid and
Nonproton Ligand.
AB - The regulation and mechanisms underlying itch sensation are complex. Here, we
report a role for acid-sensing ion channel 3 (ASIC3) in mediating itch evoked by
certain pruritogens during tissue acidosis. Co-administration of acid with Ser
Leu-Ile-Gly-Arg-Leu-NH2 (SL-NH2) increased scratching behavior in wild-type, but
not ASIC3-null, mice, implicating the channel in coincident detection of acidosis
and pruritogens. Mechanistically, SL-NH2 slowed desensitization of proton-evoked
currents by targeting the previously identified nonproton ligand-sensing domain
located in the extracellular region of ASIC3 channels in primary sensory neurons.
Ablation of the ASIC3 gene reduced dry-skin-induced scratching behavior and
pathological changes under conditions with concomitant inflammation. Taken
together, our data suggest that ASIC3 mediates itch sensation via coincident
detection of acidosis and nonproton ligands that act at the nonproton ligand
sensing domain of the channel.
PMID- 26440888
TI - Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway.
AB - Upon DNA stimulation, cyclic GMP-AMP synthase (cGAS) synthesizes the second
messenger cyclic GMP-AMP (cGAMP) that binds to the STING, triggering antiviral
interferon-beta (IFN-beta) production. However, it has remained undetermined how
hosts regulate cGAS enzymatic activity after the resolution of DNA immunogen.
Here, we show that Akt kinase plays a negative role in cGAS-mediated anti-viral
immune response. Akt phosphorylated the S291 or S305 residue of the enzymatic
domain of mouse or human cGAS, respectively, and this phosphorylation robustly
suppressed its enzymatic activity. Consequently, expression of activated Akt led
to the reduction of cGAMP and IFN-beta production and the increase of herpes
simplex virus 1 replication, whereas treatment with Akt inhibitor augmented cGAS
mediated IFN-beta production. Furthermore, expression of the phosphorylation
resistant cGAS S291A mutant enhanced IFN-beta production upon DNA stimulation,
HSV-1 infection, and vaccinia virus infection. Our study identifies an Akt kinase
mediated checkpoint to fine-tune hosts' immune responses to DNA stimulation.
PMID- 26440889
TI - Reversion of FMR1 Methylation and Silencing by Editing the Triplet Repeats in
Fragile X iPSC-Derived Neurons.
AB - Fragile X syndrome (FXS) is the most common form of inherited intellectual
disability, resulting from a CGG repeat expansion in the fragile X mental
retardation 1 (FMR1) gene. Here, we report a strategy for CGG repeat correction
using CRISPR/Cas9 for targeted deletion in both embryonic stem cells and induced
pluripotent stem cells derived from FXS patients. Following gene correction in
FXS induced pluripotent stem cells, FMR1 expression was restored and sustained in
neural precursor cells and mature neurons. Strikingly, after removal of the CGG
repeats, the upstream CpG island of the FMR1 promoter showed extensive
demethylation, an open chromatin state, and transcription initiation. These
results suggest a silencing maintenance mechanism for the FMR1 promoter that is
dependent on the existence of the CGG repeat expansion. Our strategy for deletion
of trinucleotide repeats provides further insights into the molecular mechanisms
of FXS and future therapies of trinucleotide repeat disorders.
PMID- 26440890
TI - A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression.
AB - Let-7 microRNAs (miRNAs) are critical regulators of animal development, stem cell
differentiation, glucose metabolism, and tumorigenesis. Mammalian genomes contain
12 let-7 isoforms that suppress expression of a common set of target mRNAs. LIN28
proteins selectively block let-7 biogenesis in undifferentiated cells and in
cancer. The current model for coordinate let-7 repression involves the LIN28 cold
shock domain (CSD) binding the terminal loop and the two CCHC-type zinc fingers
recognizing a GGAG sequence motif in precursor let-7 (pre-let-7) RNAs. Here, we
perform a systematic analysis of all let-7 miRNAs and find that a single let-7
family member, human let-7a-3 (and its murine ortholog let-7c-2), escapes LIN28
mediated regulation. Mechanistically, we find that the pre-let-7c-2 loop
precludes LIN28A binding and regulation. These findings refine the current model
of let-7 regulation by LIN28 proteins and have important implications for
understanding the LIN28/let-7 axis in development and disease.
PMID- 26440891
TI - Mammary Stem Cell Self-Renewal Is Regulated by Slit2/Robo1 Signaling through
SNAI1 and mINSC.
AB - Tissue homeostasis requires somatic stem cell maintenance; however, mechanisms
regulating this process during organogenesis are not well understood. Here, we
identify asymmetrically renewing basal and luminal stem cells in the mammary end
bud. We demonstrate that SLIT2/ROBO1 signaling regulates the choice between self
renewing asymmetric cell divisions (ACDs) and expansive symmetric cell divisions
(SCDs) by governing Inscuteable (mInsc), a key member of the spindle orientation
machinery, through the transcription factor Snail (SNAI1). Loss of SLIT2/ROBO1
signaling increases SNAI1 in the nucleus. Overexpression of SNAI1 increases mInsc
expression, an effect that is inhibited by SLIT2 treatment. Increased mInsc does
not change cell proliferation in the mammary gland (MG) but instead causes more
basal cap cells to divide via SCD, at the expense of ACD, leading to more stem
cells and larger outgrowths. Together, our studies provide insight into how the
number of mammary stem cells is regulated by the extracellular cue SLIT2.
PMID- 26440892
TI - Principles Governing A-to-I RNA Editing in the Breast Cancer Transcriptome.
AB - Little is known about how RNA editing operates in cancer. Transcriptome analysis
of 68 normal and cancerous breast tissues revealed that the editing enzyme ADAR
acts uniformly, on the same loci, across tissues. In controlled ADAR expression
experiments, the editing frequency increased at all loci with ADAR expression
levels according to the logistic model. Loci-specific "editabilities," i.e.,
propensities to be edited by ADAR, were quantifiable by fitting the logistic
function to dose-response data. The editing frequency was increased in tumor
cells in comparison to normal controls. Type I interferon response and ADAR DNA
copy number together explained 53% of ADAR expression variance in breast cancers.
ADAR silencing using small hairpin RNA lentivirus transduction in breast cancer
cell lines led to less cell proliferation and more apoptosis. A-to-I editing is a
pervasive, yet reproducible, source of variation that is globally controlled by
1q amplification and inflammation, both of which are highly prevalent among human
cancers.
PMID- 26440893
TI - Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the
Quiescent State and the Niche.
AB - Calcitonin receptor (Calcr) is expressed in adult muscle stem cells (muscle
satellite cells [MuSCs]). To elucidate the role of Calcr, we conditionally
depleted Calcr from adult MuSCs and found that impaired regeneration after muscle
injury correlated with the decreased number of MuSCs in Calcr-conditional
knockout (cKO) mice. Calcr signaling maintained MuSC dormancy via the cAMP-PKA
pathway but had no impact on myogenic differentiation of MuSCs in an
undifferentiated state. The abnormal quiescent state in Calcr-cKO mice resulted
in a reduction of the MuSC pool by apoptosis. Furthermore, MuSCs were found
outside their niche in Calcr-cKO mice, demonstrating cell relocation. This
emergence from the sublaminar niche was prevented by the Calcr-cAMP-PKA and Calcr
cAMP-Epac pathways downstream of Calcr. Altogether, the findings demonstrated
that Calcr exerts its effect specifically by keeping MuSCs in a quiescent state
and in their location, maintaining the MuSC pool.
PMID- 26440895
TI - Elevated RNA Editing Activity Is a Major Contributor to Transcriptomic Diversity
in Tumors.
AB - Genomic mutations in key genes are known to drive tumorigenesis and have been the
focus of much attention in recent years. However, genetic content also may change
farther downstream. RNA editing alters the mRNA sequence from its genomic
blueprint in a dynamic and flexible way. A few isolated cases of editing
alterations in cancer have been reported previously. Here, we provide a
transcriptome-wide characterization of RNA editing across hundreds of cancer
samples from multiple cancer tissues, and we show that A-to-I editing and the
enzymes mediating this modification are significantly altered, usually elevated,
in most cancer types. Increased editing activity is found to be associated with
patient survival. As is the case with somatic mutations in DNA, most of these
newly introduced RNA mutations are likely passengers, but a few may serve as
drivers that may be novel candidates for therapeutic and diagnostic purposes.
PMID- 26440896
TI - GDH-Dependent Glutamate Oxidation in the Brain Dictates Peripheral Energy
Substrate Distribution.
AB - Glucose, the main energy substrate used in the CNS, is continuously supplied by
the periphery. Glutamate, the major excitatory neurotransmitter, is foreseen as a
complementary energy contributor in the brain. In particular, astrocytes actively
take up glutamate and may use it through oxidative glutamate dehydrogenase (GDH)
activity. Here, we investigated the significance of glutamate as energy substrate
for the brain. Upon glutamate exposure, astrocytes generated ATP in a GDH
dependent way. The observed lack of glutamate oxidation in brain-specific GDH
null CnsGlud1(-/-) mice resulted in a central energy-deprivation state with
increased ADP/ATP ratios and phospho-AMPK in the hypothalamus. This induced
changes in the autonomous nervous system balance, with increased sympathetic
activity promoting hepatic glucose production and mobilization of substrates
reshaping peripheral energy stores. Our data reveal the importance of glutamate
as necessary energy substrate for the brain and the role of central GDH in the
regulation of whole-body energy homeostasis.
PMID- 26440894
TI - A Gene Regulatory Network Cooperatively Controlled by Pdx1 and Sox9 Governs
Lineage Allocation of Foregut Progenitor Cells.
AB - The generation of pancreas, liver, and intestine from a common pool of
progenitors in the foregut endoderm requires the establishment of organ
boundaries. How dorsal foregut progenitors activate pancreatic genes and evade
the intestinal lineage choice remains unclear. Here, we identify Pdx1 and Sox9 as
cooperative inducers of a gene regulatory network that distinguishes the
pancreatic from the intestinal lineage. Genetic studies demonstrate dual and
cooperative functions for Pdx1 and Sox9 in pancreatic lineage induction and
repression of the intestinal lineage choice. Pdx1 and Sox9 bind to regulatory
sequences near pancreatic and intestinal differentiation genes and jointly
regulate their expression, revealing direct cooperative roles for Pdx1 and Sox9
in gene activation and repression. Our study identifies Pdx1 and Sox9 as
important regulators of a transcription factor network that initiates pancreatic
fate and sheds light on the gene regulatory circuitry that governs the
development of distinct organs from multi-lineage-competent foregut progenitors.
PMID- 26440897
TI - Circulating Th1-Cell-type Tfh Cells that Exhibit Impaired B Cell Help Are
Preferentially Activated during Acute Malaria in Children.
AB - Malaria-specific antibody responses are short lived in children, leaving them
susceptible to repeated bouts of febrile malaria. The cellular and molecular
mechanisms underlying this apparent immune deficiency are poorly understood.
Recently, T follicular helper (Tfh) cells have been shown to play a critical role
in generating long-lived antibody responses. We show that Malian children have
resting PD-1(+)CXCR5(+)CD4(+) Tfh cells in circulation that resemble germinal
center Tfh cells phenotypically and functionally. Within this population, PD
1(+)CXCR5(+)CXCR3(-) Tfh cells are superior to Th1-polarized PD
1(+)CXCR5(+)CXCR3(+) Tfh cells in helping B cells. Longitudinally, we observed
that malaria drives Th1 cytokine responses, and accordingly, the less-functional
Th1-polarized Tfh subset was preferentially activated and its activation did not
correlate with antibody responses. These data provide insights into the Tfh cell
biology underlying suboptimal antibody responses to malaria in children and
suggest that vaccine strategies that promote CXCR3(-) Tfh cell responses may
improve malaria vaccine efficacy.
PMID- 26440898
TI - p62 Plays a Specific Role in Interferon-gamma-Induced Presentation of a
Toxoplasma Vacuolar Antigen.
AB - Also known as Sqstm1, p62 is a selective autophagy adaptor with a ubiquitin
binding domain. However, the role of p62 in the host defense against Toxoplasma
gondii infection is unclear. Here, we show that interferon gamma (IFN-gamma)
stimulates ubiquitin and p62 recruitment to T. gondii parasitophorous vacuoles
(PVs). Some essential autophagy-related proteins, but not all, are required for
this recruitment. Regardless of normal IFN-gamma-induced T. gondii clearance
activity and ubiquitination, p62 deficiency in antigen-presenting cells (APCs)
and mice diminishes the robust IFN-gamma-primed activation of CD8(+) T cells that
recognize the T. gondii-derived antigen secreted into PVs. Because the expression
of Atg3 and Irgm1/m3 in APCs is essential for PV disruption, ubiquitin and p62
recruitment, and vacuolar-antigen-specific CD8(+) T cell activation, IFN-gamma
mediated ubiquitination and the subsequent recruitment of p62 to T. gondii are
specifically required for the acquired immune response after PV disruption by IFN
gamma-inducible GTPases.
PMID- 26440900
TI - Anatomical and physiological basis for the allometric scaling of cisplatin
clearance in dogs.
AB - Cisplatin is a platinum-containing cytotoxic drug indicated for the treatment of
solid tumors in veterinary and human patients. Several of the algorithms used to
standardize the doses of cytotoxic drugs utilize allometry, or the
nonproportional relationships between anatomical and physiological variables, but
the underlying basis for these relationships is poorly understood. The objective
of this proof of concept study was to determine whether allometric equations
explain the relationships between body weight, kidney weight, renal physiology,
and clearance of a model, renally cleared anticancer agent in dogs. Postmortem
body, kidney, and heart weights were collected from 364 dogs (127 juveniles and
237 adults, including 51 dogs >= 8 years of age). Renal physiological and
cisplatin pharmacokinetic studies were conducted in ten intact male dogs
including two juvenile and eight adult dogs (4-55 kg). Glomerular filtration rate
(GFR), effective renal plasma flow, effective renal blood flow, renal cisplatin
clearance, and total cisplatin clearance were allometrically related to body
weight with powers of 0.75, 0.59, 0.61, 0.71, and 0.70, respectively. The similar
values of these diverse mass exponents suggest a common underlying basis for the
allometry of kidney size, renal physiology, and renal drug handling.
PMID- 26440899
TI - ATM Dependent Silencing Links Nucleolar Chromatin Reorganization to DNA Damage
Recognition.
AB - Resolution of DNA double-strand breaks (DSBs) is essential for the suppression of
genome instability. DSB repair in transcriptionally active genomic regions
represents a unique challenge that is associated with ataxia telangiectasia
mutated (ATM) kinase-mediated transcriptional silencing. Despite emerging
insights into the underlying mechanisms, how DSB silencing connects to DNA repair
remains undefined. We observe that silencing within the rDNA depends on
persistent DSBs. Non-homologous end-joining was the predominant mode of DSB
repair allowing transcription to resume. ATM-dependent rDNA silencing in the
presence of persistent DSBs led to the large-scale reorganization of nucleolar
architecture, with movement of damaged chromatin to nucleolar cap regions. These
findings identify ATM-dependent temporal and spatial control of DNA repair and
provide insights into how communication between DSB signaling and ongoing
transcription promotes genome integrity.
PMID- 26440901
TI - Transcatheter Treatment of Apicoaortic Conduit Dysfunction.
AB - We report a 77-year-old male patient with a history of aortic valve bypass with
an apicoaortic conduit 11 years ago for severe aortic stenosis, presenting with
acute decompensated congestive heart failure. Severe conduit valve regurgitation
and was successfully treated with transcatheter aortic valve replacement (TAVR)
of the native aortic valve using a self-expanding bioprosthesis followed by
transcatheter closure of the apicoaortic conduit.
PMID- 26440904
TI - 4th European Congrses of Immunology--Servus from Vienna!
PMID- 26440905
TI - Hobit and human effector T-cell differentiation: The beginning of a long journey.
AB - Besides growing plants, eating a lot, and drinking beer, Tolkien's Hobbits enjoy
maintaining a quiet state. Regarding the latter, the name chosen for a recently
discovered transcription factor seems to be unintentionally appropriate. The zinc
finger protein ZNF683 was originally named "Hobit" for Homolog of Blimp-1 in T
cells. In this issue of the European Journal of Immunology, Braga et al. [Eur. J.
Immunol. 2015. 45: 2945-2958] demonstrate that in humans, Hobit is almost
exclusively expressed in effector T cells, in particular in quiescent and long
lived effector-type CD8(+) T cells. Hobit may initially appear as another
"player" in the quest for transcription factors guiding T-cell differentiation;
the discoveries of T-bet, Eomes, Blimp-1, and others have significantly
contributed to our understanding of how this process is tightly regulated.
However, Hobit may be special--the currently available results suggest
substantial differences in Hobit's regulatory functions between mice and humans,
such as expression patterns and IFN-gamma regulation. And it may turn out that
Hobit's function in human T cells is highly adapted to lifelong, periodic
challenges with varying, physiological doses of pathogens. Thus, the new study
about Hobit in human T cells may be the beginning of a long journey.
PMID- 26440909
TI - Carbonylative Mizoroki-Heck Reaction of Alkyl Iodides with Arylalkenes Using a
Pd/Photoirradiation System.
AB - A carbonylative Mizoroki-Heck reaction using alkyl iodides was achieved with a
Pd/photoirradiation system using DBU as a base. In this reaction, alkyl radicals
were formed from alkyl iodides via single-electron transfer (SET) and then
underwent a sequential addition to CO and alkenes to give beta-keto radicals. It
is proposed that DBU would abstract a proton alpha to carbonyl to form radical
anions, giving alpha,beta-unsaturated ketones via SET.
PMID- 26440910
TI - CLONING AND EXPRESSING TRYPSIN MODULATING OOSTATIC FACTOR IN Chlorella desiccata
TO CONTROL MOSQUITO LARVAE.
AB - The insect peptide hormone trypsin modulating oostatic factor (TMOF), a
decapeptide that is synthesized by the mosquito ovary and controls the
translation of the gut's trypsin mRNA was cloned and expressed in the marine alga
Chlorella desiccata. To express Aedes aegypti TMOF gene (tmfA) in C. desiccata
cells, two plasmids (pYES2/TMOF and pYDB4-tmfA) were engineered with pKYLX71 DNA
(5 Kb) carrying the cauliflower mosaic virus (CaMV) promoter 35S(2) and the
kanamycin resistant gene (neo), as well as, a 8 Kb nitrate reductase gene (nit)
from Chlorella vulgaris. Transforming C. desiccata with pYES2/TMOF and pYDB4-tmfA
show that the engineered algal cells express TMOF (20 +/- 4 MUg +/- SEM and 17 +/
3 MUg +/- SEM, respectively in 3 * 10(8) cells) and feeding the cells to
mosquito larvae kill 75 and 60% of Ae. aegypti larvae in 4 days, respectively.
Southern and Northern blots analyses show that tmfA integrated into the genome of
C. desiccata by homologous recombination using the yeast 2 MU circle of
replication and the nit in pYES2/TMOF and pYDB4-tmfA, respectively, and the
transformed algal cells express tmfA transcript. Using these algal cells it will
be possible in the future to control mosquito larvae in the marsh.
PMID- 26440911
TI - Fasciola hepatica mucin-encoding gene: expression, variability and its potential
relevance in host-parasite relationship.
AB - Fasciola hepatica is the causative agent of fasciolosis, a zoonosis with
significant impact both in human and animal health. Understanding the basic
processes of parasite biology, especially those related to interactions with its
host, will contribute to control F. hepatica infections and hence liver
pathology. Mucins have been described as important mediators for parasite
establishment within its host, due to their key roles in immune evasion. In F.
hepatica, mucin expression is upregulated in the mammalian invasive newly
excysted juvenile (NEJ) stage in comparison with the adult stage. Here, we
performed sequencing of mucin cDNAs prepared from NEJ RNA, resulting in six
different cDNAs clusters. The differences are due to the presence of a tandem
repeated sequence of 66 bp encoded by different exons. Two groups of apomucins
one with three and the other with four repeats, with 459 and 393 bp respectively,
were identified. These cDNAs have open reading frames encoding Ser-Thr enriched
proteins with an N-terminal signal peptide, characteristic of apomucin backbone.
We cloned a 4470 bp gene comprising eight exons and seven introns that encodes
all the cDNA variants identified in NEJs. By real time polymerase chain reaction
and high-resolution melting approaches of individual flukes we infer that fhemuc
1 is a single-copy gene, with at least two different alleles. Our data suggest
that both gene polymorphism and alternative splicing might account for apomucin
variability in the fhemuc-1 gene that is upregulated in NEJ invasive stage. The
relevance of this variation in host-parasite interplay is discussed.
PMID- 26440912
TI - Significant Misuse of Sildenafil in London Nightclubs.
AB - BACKGROUND: There is anecdotal evidence of misuse of erectile dysfunction
medication, particularly to counteract some of the unwanted effects of
recreational drugs on erectile function. However, there is little data from the
United Kingdom (UK). AIM: To evaluate the prevalence of sildenafil misuse in a UK
population that has previously been shown to have high recreational drug use.
DESIGN: Questionnaire survey. METHODS: Individuals attending nightclubs catering
for the men who have sex with men (MSM) community in South London were asked
about lifetime and last year use of recreational drugs and sildenafil. RESULTS:
313 individuals were surveyed over four nights in 2013: 282 (90.1%) were males
and 248 (79.2%) were MSM. Last year use of recreational drugs was high:
mephedrone (74.1%), cocaine (61.3%), MDMA/Ecstasy (59.2%), GHB/GBL (52.8%),
cannabis (51.8%), and ketamine (50%). 136 (49.1%) MSM versus 6 (18.8%) non-MSM
clubbers had misused sildenafil in the last year (p < .001). Amongst the MSM
clubbers, 232 (93.5%) had heard of sildenafil, 161 (64.9%) reported misuse of
sildenafil in their lifetime and 133 (53.6%) had misused sildenafil in the last
year. CONCLUSION: This study demonstrates a high prevalence of sildenafil misuse
in a population who are heavy users of recreational drugs; it is not likely that
this young population have underlying erectile dysfunction as a reason for
legitimate sildenafil use. There is the potential for interaction with other
recreational drugs used including cocaine and volatile nitrites. Further work is
required in to determine the extent and reason for the misuse.
PMID- 26440914
TI - Broadband quantitative phase microscopy with extended field of view using off
axis interferometric multiplexing.
AB - We propose a new portable imaging configuration that can double the field of view
(FOV) of existing off-axis interferometric imaging setups, including broadband
off-axis interferometers. This configuration is attached at the output port of
the off-axis interferometer and optically creates a multiplexed interferogram on
the digital camera, which is composed of two off-axis interferograms with
straight fringes at orthogonal directions. Each of these interferograms contains
a different FOV of the imaged sample. Due to the separation of these two FOVs in
the spatial-frequency domain, they can be fully reconstructed separately, while
obtaining two complex wavefronts from the sample at once. Since the optically
multiplexed off-axis interferogram is recorded by the camera in a single
exposure, fast dynamics can be recorded with a doubled imaging area. We used this
technique for quantitative phase microscopy of biological samples with extended
FOV. We demonstrate attaching the proposed module to a diffractive phase
microscopy interferometer, illuminated by a broadband light source. The
biological samples used for the experimental demonstrations include microscopic
diatom shells, cancer cells, and flowing blood cells.
PMID- 26440915
TI - Strong Coupling between the Hydrogen Bonding Environment and Redox Chemistry
during the S2 to S3 Transition in the Oxygen-Evolving Complex of Photosystem II.
AB - We have studied the early phase of the S2 -> S3 transition in the oxygen-evolving
complex (OEC) of photosystem II using the hybrid density functional theory with a
quantum mechanical model composed of 338-341 atoms. Special attention is given to
the vital role of water molecules in the vicinity of the Mn4CaO5 core. Our
results demonstrate how important the dynamic behavior of surrounding water
molecules is in mediating critical chemical transformations such as binding and
deprotonation of substrates and hydration of the catalytic site and identify a
strong coupling of water-chain relocation near the redox-active tyrosine residue
Tyr161 (TyrZ) with oxidation of the Mn4CaO5 cluster by TyrZ(*+). The oxidation
reaction is further promoted when the catalytic site is more solvated by water.
These results indicate the importance of surrounding water molecules in
biological catalysts as they ultimately lead to effective catalytic function
and/or favorable electron-transfer dynamics.
PMID- 26440913
TI - Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses
identified during vaccine trial in Africa.
AB - RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic
backbone in vitro reassorted with human outer capsid genes. During clinical
trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year
follow-up was lower against the genotypes contained in the vaccine than against
the heterotypic G8P[6] and G8P[1] rotavirus strains of which the former is highly
prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes
collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa,
were conducted to gain insight into the high level of cross-protection afforded
by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the
presence of a high number of bovine rotavirus gene segments in these human G8
strains. In addition, we performed an in depth analysis on the individual amino
acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM
vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic
backbone, the high vaccine efficacy against G8 strains might be partially
explained by the fact that all these strains contain a complete or partial bovine
like backbone. Altogether, this study supports the hypothesis that gene segments
other than VP7 and VP4 play a role in vaccine-induced immunity.
PMID- 26440916
TI - Prevention of post operative complications following surgical treatment of equine
colic: Current evidence.
AB - Changes in management of the surgical colic patient over the last 30 years have
resulted in considerable improvement in post operative survival rates. However,
post operative complications remain common and these impact negatively on horse
welfare, probability of survival, return to previous use and the costs of
treatment. Multiple studies have investigated risk factors for post operative
complications following surgical management of colic and interventions that might
be effective in reducing the likelihood of these occurring. The findings from
these studies are frequently contradictory and the evidence for many
interventions is lacking or inconclusive. This review discusses the current
available evidence and identifies areas where further studies are necessary and
factors that should be taken into consideration in study design.
PMID- 26440918
TI - Design Model Parameter Analysis for Nitrifying Trickling Filters.
AB - Nitrifying trickling filters (NTFs) represent an effective technology for water
resource recovery facilities (WRRFs) to achieve compliance with ammonia-N
permits. However, while the potential benefits of NTFs are many, the design
methods and associated parameter databases are underdeveloped. Research herein
focused on analysis of pilot-scale NTF data to develop enhanced design guidance.
rn(max,0) values ranged from 1.19-3.38 gN m-2*d-1, and correlated with influent
ammonia-N concentration and loading. The transition concentration from rn(max,0)
ranged from 0.9-22.2 mgN/L, and correlated with ammonia-N loading. Zero-order
nitrification ranging from 0.24-1.58 gN m-2*d-1 was observed down-gradient of
rn(max,0). First-order nitrification was not observed, nor was there a strong
exponential correlation for decreasing nitrification rate. To translate results
to NTF media different from that utilized, a relationship between the NTF media
effectiveness parameter, E, and rn(max,0) was established. Collectively, the data
presented enhances the engineer's ability to model and design NTFs.
PMID- 26440917
TI - Genome-wide significant linkage of schizophrenia-related neuroanatomical trait to
12q24.
AB - The insula and medial prefrontal cortex (mPFC) share functional, histological,
transcriptional, and developmental characteristics, and they serve higher
cognitive functions of theoretical relevance to schizophrenia and related
disorders. Meta-analyses and multivariate analysis of structural magnetic
resonance imaging (MRI) scans indicate that gray matter density and volume
reductions in schizophrenia are the most consistent and pronounced in a network
primarily composed of the insula and mPFC. We used source-based morphometry, a
multivariate technique optimized for structural MRI, in a large sample of
randomly ascertained pedigrees (N = 887) to derive an insula-mPFC component and
to investigate its genetic determinants. Firstly, we replicated the insula-mPFC
gray matter component as an independent source of gray matter variation in the
general population, and verified its relevance to schizophrenia in an independent
case-control sample. Secondly, we showed that the neuroanatomical variation
defined by this component is largely determined by additive genetic variation
(h(2) = 0.59), and genome-wide linkage analysis resulted in a significant
linkage peak at 12q24 (LOD = 3.76). This region has been of significant interest
to psychiatric genetics as it contains the Darier's disease locus and other
proposed susceptibility genes (e.g., DAO, NOS1), and it has been linked to
affective disorders and schizophrenia in multiple populations. Thus, in
conjunction with previous clinical studies, our data imply that one or more
psychiatric risk variants at 12q24 are co-inherited with reductions in mPFC and
insula gray matter concentration. (c) 2015 Wiley Periodicals, Inc.
PMID- 26440919
TI - Synthesis of virtually enantiopure aminodiols with three adjacent stereogenic
centers by epoxidation and ring-opening.
AB - A virtually complete enantioselective synthesis of 3-amino-1,2-diols with three
consecutive stereocenters was accomplished by a sequential cascade of two kinetic
resolutions, which features a Sharpless or Hafnium-catalyzed asymmetric
epoxidation and a subsequent W-catalyzed aminolysis. Enantiopure products with up
to >99.9% ee and >99.9 : 0.1 dr were obtained and could serve as potential
building blocks for pharmaceutical or biological significant molecules.
PMID- 26440921
TI - Editorial Comment on "Bias in Evaluating Erectile Function in Lifelong Premature
Ejaculation Patients with the International Index of Erectile Function-5".
PMID- 26440920
TI - Changing of bloodstream infections in a medical center neonatal intensive care
unit.
AB - BACKGROUND/PURPOSE: Bloodstream infections (BSIs) are associated with high
mortality and morbidity in neonatal intensive care units (NICUs). The
epidemiology of these infections may change after the application of new
infection control policies. The aims of this study are to reveal the changing
epidemiology of BSIs in our NICU and inspect the effects of infection control
efforts. METHODS: We reviewed and analyzed the clinical characteristics of
culture-proven BSIs in our NICU from 2008 to 2013 and compared them with our two
previously reported data (1992-2001 and 2002-2007). RESULTS: The mortality rate
decreased from 16.3% in 1992-2001 to 5.6% in 2008-2013. In the recent study
period, Gram-positive infections became predominant (58.0%). Coagulase-negative
staphylococci remained the most commonly isolated organisms (26.0%). Group B
Streptococcus (GBS) BSIs had the highest mortality rate (30.0%). Most GBS
infected infants' mother did not perform prenatal GBS screening. There was a
decrease in the total fungal infection rate after fluconazole prophylaxis for
very-low-birth-weight (VLBW) neonates, but the infections of fluconazole
resistant Malassezia pachydermatis increased. The incidence of central line
associated BSI increased to 10.6% in 2011. After restricting the catheter
duration to <21 days, the incidence decreased to 4.2% in 2013. CONCLUSION:
Through the years, the overall mortality rate of BSIs in our NICU decreased.
Maternal GBS screening is an important issue for avoiding early onset GBS
mortality. Fungal infection rate decreased after antifungal prophylaxis policy
for VLBW infants, but we should be aware of resistant strains. Restriction of the
catheter duration may decrease the incidence of catheter-related BSI.
PMID- 26440922
TI - Mammalian Host-Versus-Phage immune response determines phage fate in vivo.
AB - Emerging bacterial antibiotic resistance draws attention to bacteriophages as a
therapeutic alternative to treat bacterial infection. Examples of phage that
combat bacteria abound. However, despite careful testing of antibacterial
activity in vitro, failures nevertheless commonly occur. We investigated
immunological response of phage antibacterial potency in vivo. Anti-phage
activity of phagocytes, antibodies, and serum complement were identified by
direct testing and by high-resolution fluorescent microscopy. We accommodated the
experimental data into a mathematical model. We propose a universal schema of
innate and adaptive immunity impact on phage pharmacokinetics, based on the
results of our numerical simulations. We found that the mammalian-host response
to infecting bacteria causes the concomitant removal of phage from the system. We
propose the notion that this effect as an indirect pathway of phage inhibition by
bacteria with significant relevance for the clinical outcome of phage therapy.
PMID- 26440923
TI - Effects of vitamin D supplementation as an adjuvant therapy in coronary artery
disease patients.
AB - OBJECTIVES: Low vitamin D status has been shown to be associated with coronary
artery disease. We planned to research the effects of vitamin D3 supplementation
on the severity of coronary artery disease. DESIGN: We investigated the effect of
0.5 MUg vitamin D3 per day in a randomized, placebo-controlled, double-blind
study in 90 stable coronary artery disease patients residing in Beijing. Coronary
angiography was performed before and after 6 months of treatment that took place
between January and June. 25-Hydroxyvitamin D was measured by chemiluminescence
assay. Coronary artery disease severity was assessed by using the SYNTAX scores.
RESULTS: In vitamin D supplementation group, there was a significant increase in
mean 25-hydroxyvitamin D levels from baseline (19.9 +/- 9.8 ng/ml) to 6 months
(35.8 +/- 12.1 ng/ml; p < 0.001). At 6 months, the primary end point, a
difference in the fall of SYNTAX score between the groups was -2.5 (95% CI -5.1
to -0.5; p < 0.001) under intention to treat analysis. Compared with the control
group, patients treated with vitamin D3 also had greater decreases in high
sensitivity C-reactive protein and renin-angiotensin system activity (p < 0.05).
CONCLUSIONS: Vitamin D supplementation has beneficial effects on coronary artery
disease; it can be an adjuvant therapy for patients with coronary artery disease.
PMID- 26440924
TI - Carriage of Haemophilus influenzae in the oropharynx of young children and
molecular epidemiology of the isolates after fifteen years of H. influenzae type
b vaccination in Italy.
AB - BACKGROUND: Haemophilus influenzae is an important pathogen able to cause a wide
spectrum of diseases in children. Colonization of the upper respiratory tract is
a risk factor for developing disease. This study aimed to investigate the
oropharyngeal carriage rate of H. influenzae in young children in two Italian
cities, 15 years after H. influenzae type b (Hib) vaccination was introduced.
Antibiotic resistant traits and genotypes of the colonizing H. influenzae
isolates were investigated. METHODS: Oropharyngeal swabs were obtained from 717
healthy children aged <6 years (June 2012-July 2013). Potential risk factors for
H. influenzae colonization were investigated. H. influenzae isolates from
carriage were characterized by PCR capsular typing, ampicillin susceptibility
testing, resistance-associated gene sequencing and multilocus sequence typing
(MLST). For comparison purposes, 38 non-typeable H. influenzae (NTHi) isolates
from invasive disease were genotyped by MLST. RESULTS: The overall H. influenzae
carriage rate was 14.1% (101/717). Age, study site, presence of young siblings,
and complete Hib vaccination status were independently associated with
colonization. Of 101 isolates, 98 were NTHi, 2 were type e and 1 was type f. The
overall ampicillin resistance rate was 15.8% (16/101). Resistance was mediated by
TEM-1 beta-lactamase production in half of isolates (n=8) or modifications in
penicillin-binding protein (PBP) 3 in the other half (n=8). Several substitutions
were discovered in PBP3 including the Asn526Lys change. Seventy-six different STs
were identified among 98 NTHi isolates from carriage, with only 4 STs (ST12,
ST57, ST238, ST1238) encompassing >= 3 isolates. Comparison of carriage and
disease isolates found that several STs were shared between the two sources,
although none of the major disease-associated STs were observed in carriage
isolates. CONCLUSIONS: NTHi is the predominant serotype in carriage. The
importance of monitoring both NTHi colonization rate and circulating genotypes
should be emphasized in the era of the Hib conjugate vaccines.
PMID- 26440925
TI - Unmasking in an observational vaccine safety study: Using type 2 diabetes
mellitus as an example.
AB - BACKGROUND: In observational vaccine safety studies, diagnosis codes assigned
prior to or on the day of vaccination (Day 0) are often excluded from analysis of
safety signals since they usually represent pre-existing conditions. The
limitations of this approach have been described for autoimmune conditions but
not for other chronic conditions. We draw on our experience in a post-licensure
quadrivalent human papillomavirus vaccine (HPV4) safety study to examine the
effectiveness of exclusion of pre-existing and Day 0 diagnoses of type 2 diabetes
mellitus (T2DM) in excluding prevalent T2DM. METHODS: Subjects included all
117,402 females ages 9-26 years who received HPV4 August 2006-March 2008 in
Kaiser Permanente Southern California. We identified potential incident T2DM
cases using ICD9 code 250.xx associated with inpatient and emergency room visits
during the 60 days following each HPV4 dose, excluding those with this code prior
to their first HPV4 dose. Electronic medical records were reviewed to determine
the dates of symptom onset, diagnostic labs, vaccine administration and T2DM
diagnosis. RESULTS: Of 33 potential incident T2DM cases identified using
automated data, 4 (12%) were confirmed to have new onset T2DM after medical
record review. Nineteen cases were excluded that did not have T2DM or had T2DM
diagnosed before Day 0; nine had an abnormal fasting blood sugar (FBS) ordered on
Day 0, prompting subsequent evaluation and diagnosis of T2DM; and one had
elevated FBS and glucosuria prior to the first dose of HPV4 but T2DM diagnosed at
a visit following vaccination. CONCLUSION: These results suggest that among
adolescents and young adults, the workup and subsequent diagnosis of pre-existing
conditions may result from a visit at which a vaccination is administered. This
"unmasking" phenomenon is not entirely eliminated by exclusion of pre-existing
and Day 0 diagnoses. Medical record review should be considered in the evaluation
of potential safety signals.
PMID- 26440926
TI - Comparison of different methods to include recycling in LCAs of aluminium cans
and disposable polystyrene cups.
AB - Many methods have been reported and used to include recycling in life cycle
assessments (LCAs). This paper evaluates six widely used methods: three
substitution methods (i.e. substitution based on equal quality, a correction
factor, and alternative material), allocation based on the number of recycling
loops, the recycled-content method, and the equal-share method. These six methods
were first compared, with an assumed hypothetical 100% recycling rate, for an
aluminium can and a disposable polystyrene (PS) cup. The substitution and
recycled-content method were next applied with actual rates for recycling,
incineration and landfilling for both product systems in selected countries. The
six methods differ in their approaches to credit recycling. The three
substitution methods stimulate the recyclability of the product and assign
credits for the obtained recycled material. The choice to either apply a
correction factor, or to account for alternative substituted material has a
considerable influence on the LCA results, and is debatable. Nevertheless, we
prefer incorporating quality reduction of the recycled material by either a
correction factor or an alternative substituted material over simply ignoring
quality loss. The allocation-on-number-of-recycling-loops method focusses on the
life expectancy of material itself, rather than on a specific separate product.
The recycled-content method stimulates the use of recycled material, i.e. credits
the use of recycled material in products and ignores the recyclability of the
products. The equal-share method is a compromise between the substitution methods
and the recycled-content method. The results for the aluminium can follow the
underlying philosophies of the methods. The results for the PS cup are
additionally influenced by the correction factor or credits for the alternative
material accounting for the drop in PS quality, the waste treatment management
(recycling rate, incineration rate, landfilling rate), and the source of avoided
electricity in case of waste incineration. The results for the PS cup, which are
less dominated by production of virgin material than aluminium can, furthermore
depend on the environmental impact categories. This stresses the importance to
consider other impact categories besides the most commonly used global warming
impact. The multitude of available methods complicates the choice of an
appropriate method for the LCA practitioner. New guidelines keep appearing and
industries also suggest their own preferred method. Unambiguous ISO guidelines,
particularly related to sensitivity analysis, would be a great step forward in
making more robust LCAs.
PMID- 26440927
TI - Erv14 cargo receptor participates in yeast salt tolerance via its interaction
with the plasma-membrane Nha1 cation/proton antiporter.
AB - The yeast Nha1p Na(+), K(+)/H(+) antiporter has a house-keeping role in pH and
cation homeostasis. It is also needed to alleviate excess Na(+) or K(+) from the
cytoplasm under high external concentrations of these cations. Erv14p, a putative
cargo receptor for transmembrane proteins is required for trafficking of Nha1p
from the endoplasmic reticulum to the plasma membrane. Sensitivity to high Na(+)
concentrations of the erv14 mutant associated to the intracellular
mislocalization of Nha1p-GFP, together with a lower Na(+) efflux, indicate the
involvement of this mutual association to accomplish the survival of the yeast
cell upon sodium stress. This observation is supported by the protein-protein
interaction between Erv14p and Nha1p detected by the mating-based Split Ubiquitin
System and co-immunoprecipitation assays. Our results indicate that even though
Erv14p interacts with Nha1p through the TMD, the C-terminal is important not only
for the efficient delivery of Nha1p to the plasma membrane but also for its
dimerization to accomplish its role in yeast salt tolerance.
PMID- 26440928
TI - Trace Element Content of Monovarietal and Commercial Portuguese Olive Oils.
AB - Olive (Olea europaea L.) represents one of the most important and ancient crops
in the Mediterranean countries, being widely known due to the optimal
organoleptic characteristics of its oil, besides the important health benefits
assigned to this product in the last few years. Since olive oil composition,
respecting specific trace elements, has a direct impact on the quality and safety
of this product, eleven monovarietal and twelve commercial olive oils were
analysed spectrometrically concerning their metal composition. Regarding quality
parameters, the monovarietal olive oils display larger quantities of Mg, Fe, Mn,
while the commercial samples are characterized by greater amounts of Na, Ca, Cu
and Zn. In which respects to safety parameters, the commercial samples present
higher values for Al and Pb, and lower quantities of Cd, respecting the
monovarietal ones. The assessment of the values observed for the trace elements,
resorting to multivariate statistical methods, allowed to clearly distinguish the
type of olive oil production-monovarietal or commercial blend. For this purpose,
besides Cluster analysis, the data have been subjected to Principal Component
Analysis-undertaken for either all the evaluated parameters simultaneously, or
the quality/safety parameters separately, both data sets allowing the
discrimination of the samples.
PMID- 26440930
TI - Development of a Dinitrosyl Iron Complex Molecular Catalyst into a Hydrogen
Evolution Cathode.
AB - Despite extensive efforts, the electrocatalytic reduction of water using
homogeneous/heterogeneous Fe, Co, Ni, Cu, W, and Mo complexes remains challenging
because of issues involving the development of efficient, recyclable, stable, and
aqueous-compatible catalysts. In this study, evolution of the de novo designed
dinitrosyl iron complex DNIC-PMDTA from a molecular catalyst into a solid-state
hydrogen evolution cathode, considering all the parameters to fulfill the
electronic and structural requirements of each step of the catalytic cycle, is
demonstrated. DNIC-PMDTA reveals electrocatalytic reduction of water at neutral
and basic media, whereas its deposit on electrode preserves exceptional
longevity, 139 h. This discovery will initiate a systematic study on the assembly
of [Fe(NO)2] motif into current collector for mass production of H2, whereas the
efficiency remains tailored by its molecular precursor [(L)Fe(NO)2].
PMID- 26440929
TI - Identification of germline genetic mutations in patients with pancreatic cancer.
AB - BACKGROUND: Pancreatic adenocarcinoma (PAC) is part of several cancer
predisposition syndromes; however, indications for genetic counseling/testing are
not well-defined. In the current study, the authors sought to determine mutation
prevalence and characteristics that are predictive of an inherited predisposition
for PAC. METHODS: A total of 175 consecutive patients with PAC who underwent
clinical genetics assessment at Memorial Sloan Kettering Cancer Center between
2011 and 2014 were identified. Clinical data, family history, and germline
results were evaluated. RESULTS: Among 159 patients with PAC who pursued genetic
testing, 24 pathogenic mutations were identified (15.1%; 95% confidence interval,
9.5%-20.7%), including BRCA2 (13 mutations), BRCA1 (4 mutations), p16 (2
mutations), PALB2 (1 mutation), and Lynch syndrome (4 mutations). BRCA1/BRCA2
prevalence was 13.7% in Ashkenazi Jewish (AJ) patients (95 patients) and 7.1% in
non-AJ patients (56 patients). In AJ patients with a strong, weak, or absent
family history of BRCA-associated cancers, the mutation prevalence was 16.7%,
15.8%, and 7.4%, respectively. The mean age at the time of diagnosis in all
mutation carriers was 58.5 years (range, 45-75 years) compared with 64 years
(range, 27-87 years) in those not carrying a mutation (P = .02). Although BRCA2
was the most common mutation identified, no patients with early-onset PAC
(diagnosed at age <= 50 years) harbored a BRCA2 mutation and the mean age at
diagnosis in BRCA2 carriers was equivalent to that of individuals who were not
mutation carriers (P = .34). Mutation prevalence in patients with early-onset
disease (21 patients) was 28.6%, including BRCA1 (2 mutations), p16 (2
mutations), MSH2 (1 mutation), and MLH1 (1 mutation). CONCLUSIONS: Mutations in
BRCA2 account for > 50% of patients with PAC with an identified susceptibility
syndrome. AJ patients were found to have high BRCA1/BRCA2 prevalence regardless
of personal/family history, suggesting that ancestry alone indicates a need for
genetic evaluation. With the exception of BRCA2-associated PAC, an inherited
predisposition for PAC is associated with an earlier age at PAC diagnosis,
suggesting that this subset of patients may also represent a population
warranting further evaluation.
PMID- 26440931
TI - A Rare Intermetatarsal Coalition With Rigid Fifth Metatarsal Deformity and
Symptomatic Plantar Lesion.
AB - Coalition or synostosis of the foot is a relatively uncommon abnormality. Some
cases of synostosis of the foot, primarily involving the midfoot and hindfoot,
have been reported. However, intermetatarsal coalition is extremely rare, with
only a small number of cases reported. We report a case of a unilateral,
congenital metatarsal coalition between the fourth and fifth metatarsal bones in
a 27-year-old female. She had initially been referred because of a symptomatic
plantar lesion under the fifth metatarsal head. Surgery consisted of separating
the affected metatarsals, combined with a proximal osteotomy, which proved
successful in establishing pain-free and more natural weightbearing.
PMID- 26440932
TI - Surgical Treatment of Calcaneal Avulsion Fracture in Elderly Patients Using
Cannulated Cancellous Screws and Titanium Wire.
AB - Avulsion fractures of the calcaneus are relatively uncommon and are seen most
frequently in elderly or osteoporotic patients. A surgical method that avoids
displacement of the avulsed fragment after fixation has not been developed. We
report the cases of 3 patients (a 73-year-old male, an 85-year-old male, and an
81-year-old female) treated by open reduction and internal fixation using
titanium wire and cannulated cancellous screws. The posterior approach was used
by way of a vertical midline incision. The fracture was fixed with 2 screws, and
then a titanium wire was passed through the holes of the cannulated screws. A
small incision on the lateral side of planter was added for the exit and return
of the wire. The wire knot was bent inside the proximal Achilles tendon bursa in
2 patients and was directed to the plantar side in 1 to avoid irritation. Bony
union was achieved without repeat displacement of the fragment in all 3 patients.
Normal ankle function was restored, and the patients recovered the activities of
daily living almost to the original level. Although an additional plantar
incision is required, this surgical technique provides strong internal fixation.
PMID- 26440933
TI - Pronounced polarization-induced energy level shifts at boundaries of organic
semiconductor nanostructures.
AB - Organic semiconductor devices rely on the movement of charge at and near
interfaces, making an understanding of energy level alignment at these boundaries
an essential element of optimizing materials for electronic and optoelectronic
applications. Here we employ low temperature scanning tunneling microscopy and
spectroscopy to investigate a model system: two-dimensional nanostructures of the
prototypical organic semiconductor, PTCDA (3,4,9,10-perylenetetracarboxylic
dianhydride) adsorbed on NaCl (2 ML)/Ag(111). Pixel-by-pixel scanning tunneling
spectroscopy allows mapping of occupied and unoccupied electronic states across
these nanoislands with sub-molecular spatial resolution, revealing strong
electronic differences between molecules at the edges and those in the centre,
with energy level shifts of up to 400 meV. We attribute this to the change in
electrostatic environment at the boundaries of clusters, namely via polarization
of neighbouring molecules. The observation of these strong shifts illustrates a
crucial issue: interfacial energy level alignment can differ substantially from
the bulk electronic structure in organic materials.
PMID- 26440934
TI - Empathy levels in undergraduate paramedic students: A three-year longitudinal
study.
AB - Empathetic behaviour is regarded as a positive trait amongst healthcare
professionals and has been attributed to increased patient compliance, greater
patient satisfaction, and greater diagnostic accuracy and reduced rates of
clinical errors. In particular, paramedic students have typically displayed lower
rates of empathy when compared to their healthcare counterparts. The objective of
this study is to assess both the level of empathy and changes in empathy in
undergraduate paramedic students over a 3-year period at a single tertiary
institution. A cross sectional study employing a convenience sample of first,
second and third year undergraduate paramedic students at Monash University.
Student empathy scores where measured with the Jefferson Scale of Empathy-Health
Profession Student version (JSE-HPS); a validated, self-reporting questionnaire.
552 students were enrolled in the study. The mean overall JSE-HPS score for the
cohort was 108.60 (SD = 12.50). Female students displayed significantly higher
empathy scores of 110.27 (SD = 11.62) compared to males at 105.36 (SD = 13.57).
There was also a significant difference (p = 0.03) noted between the 2008 JSE-HPS
score 106.32 (SD = 14.02), when compared to the 2009 cohort, 110.18 (SD = 12.91).
Results from this study suggest that paramedic students display lower empathy
than those reported by fellow healthcare students within the literature.
PMID- 26440935
TI - The prevalence of monosodium urate and calcium pyrophosphate crystals in synovial
fluid from wrist and finger joints.
AB - The aim of this study was to assess the frequency of monosodium urate (MSU) and
calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from
wrist and finger joints of patients with previously diagnosed joint diseases. We
reviewed the results of SF analysis of 1593 samples and identified 126 patients
with effusions in the small joints of the hands and wrists. We reported from
patients' medical files data about sex, age, diagnosis, disease duration and the
microscopic SF results. The prevalence of CPP crystals in SF was 85.71% in CPP
crystals arthritis (CPP-CA), 19.35% in rheumatoid arthritis (RA), 13.89% in
osteoarthritis (OA) and 0% in psoriatic arthritis (PsA), spondyloarthritis (SpA),
gout and miscellanea. The prevalence of MSU crystals in SF was 83.3% in gout, 10%
in PsA, 2.8% in OA and 0% in RA, SpA, miscellanea and CPP-CA. Consistent with
previously reported data concerning the big joints, microcrystals can be
frequently found also in the small joints of patients with previous diagnosis.
The finding underlines the importance of analyzing SF from the hand and wrist
joints in the attempt to identify comorbidities associated with the presence of
crystals and to develop targeted treatment strategies.
PMID- 26440936
TI - Serum IL-10 Predicts Worse Outcome in Cancer Patients: A Meta-Analysis.
AB - BACKGROUND: IL-10 is an important immunosuppressive cytokine which is frequently
elevated in tumor microenvironment. Some studies have reported that
overexpression of serous IL-10 is correlated with worse outcome in patients with
malignant tumor. Here, we conducted a meta-analysis to assess the prognostic
impact of serous IL-10 expression in cancer patients. METHODS: We searched PubMed
and EBSCO for studies in evaluating the association of IL-10 expression-in serum
and clinical outcome in cancer patients. Overall survival (OS) was the primary
prognostic indicator and disease-free survival (DFS) was the secondary indicator.
Extracted data were computed into odds ratios (ORs) and 95% confidence interval
(CI) or a P value for survival at 1, 3 and 5 years. Pooled data were weighted
using the Mantel-Haenszel Fixed-effect model. All statistical tests were two
sided. RESULTS: A total of 1788 patients with cancer from 21 published studies
were incorporated into this meta-analysis. High level of serum IL-10 was
significantly associated with worse OS at 1-year (OR = 3.70, 95% CI = 2.81 to
4.87, P < 0.00001), 3-year (OR = 3.33, 95% CI = 2.53 to 4.39, P < 0.0001) and 5
year (OR = 2.80, 95% CI = 1.90 to 4.10, P < 0.0001) of cancer. Subgroup analysis
showed that the correlation between serous IL-10 expression and outcome of
patients with solid tumors and hematological malignancies are consistent. The
association of IL-10 with worse DFS at 1-year (OR = 3.34, 95% CI = 1.40 to 7.94,
P = 0.006) and 2-year (OR = 3.91, 95% CI = 1.79 to 8.53, P = 0.0006) was also
identified. CONCLUSIONS: High expression of serous IL-10 leads to an adverse
survival in most types of cancer. IL-10 is a valuable biomarker for prognostic
prediction and targeting IL-10 treatment options for both solid tumors and
hematological malignancies.
PMID- 26440938
TI - Religiosity and youth substance use in a Muslim context.
AB - The literature shows that young people are more vulnerable than adults to
substance use. Religiosity is one of the factors that has been considered to
protect youth from substance use and has also been interpreted as contributing to
the substance abuse recovery process. Conceptualizing religiosity as a
multidimensional construct, this study aimed to investigate the influence of
religiosity on substance use among youth. Three dimensions of religiosity-belief
about religion, religious self-practice, and religious social environment-were
examined as predictors of substance use. The survey data collected in 2010 by the
Governance of Istanbul, Istanbul Department of Education, and Istanbul Police
Department were used. Participants were high school students (n = 31,272) between
14 and 18 years old. Structural equation modeling was used for statistical
analysis and hypothesis testing. The study found a negative relationship between
the three dimensions of religiosity and substance use. Religious social
environment was found to be the strongest of the three dimensions. The findings
suggest that religion has the potential to reduce the risk of substance use among
youth. Implications for future research and policymakers were also discussed.
PMID- 26440937
TI - Family Violence and Maltreatment of Women During the Perinatal Period:
Associations with Infant Morbidity in Indian Slum Communities.
AB - OBJECTIVES: To determine the prevalence of non-violent, gender-based forms of
maltreatment of women by husbands and in-laws [i.e., gender-based household
maltreatment (GBHM)] during pregnancy and postpartum; to clarify the role of GBHM
in compromising infant health, and whether this role extends beyond that
previously observed for intimate partner violence (IPV). METHODS: Cross
sectional, quantitative data were collected from women (ages 15-35) seeking
immunizations for their infants <6 months of age (N = 1061) in urban health
centers in Mumbai, India. Logistic regression models were constructed to assess
associations between maternal abuse (perinatal IPV, in-law violence and GBHM) and
recent infant morbidity (diarrhea, respiratory distress, fever, colic and
vomiting). RESULTS: More than one in four women (28.4%) reported IPV during their
recent pregnancy and/or during the postpartum period, 2.6% reported perinatal
violence from in-laws, and 49.0% reported one or more forms of perinatal GBHM. In
adjusted regression models that included all forms of family violence and
maltreatment, perinatal GBHM remained significantly associated with infant
morbidity (AORs 1.4-1.9); perinatal IPV and in-law violence ceased to predict
infant morbidity in models including GBHM. CONCLUSIONS: Findings indicate that
non-violent expressions of gender inequity (e.g., nutritional deprivation,
deprivation of sleep, blocking access to health care during pregnancy) are more
strongly associated with poor infant health than physical or sexual violence from
husbands or in-laws in urban India. These results strongly suggest the need to
expand the conception of gender inequities beyond IPV to include non-violent
forms of gendered mistreatment in considering their impact on infant health.
PMID- 26440939
TI - Increased Steroid Excretion in Children with Extremely Low Birth Weight at a
Median Age of 9.8 years.
AB - BACKGROUND: Events during foetal or early extrauterine life may affect bodily
structure and/or functions and even pave the way for adult diseases. AIMS: To
find whether extremely low birth weight (ELBW) infants differ from healthy
controls regarding the excretion of steroid metabolites. METHODS: The study
compared 17 female and 10 male ELBW infants, all prepubertal, aged 8-11 years,
birth weight <1,000 g, with 27 age- and sex-matched controls. All were healthy at
the time of the study. Height, weight and BMI did not differ between the groups.
Results were adjusted according to body surface area. 36 urinary steroid
metabolites were quantified by gas chromatography-mass spectrometry. RESULTS: In
the ELBW girls 33/36 steroid metabolites were higher (19 significantly) than in
the controls. All 36 steroid metabolites were higher in the ELBW boys (9
significantly) than in the controls. Sums of mineralocorticoid precursors,
metabolites descriptive for cortisol and parameters of adrenal androgen
production were significantly higher in ELBW infants (both sexes). Only the sum
of the metabolites known to be illustrative for adrenal 11beta-hydroxysteroid
dehydrogenase activity was not different. CONCLUSION: Prepubertal ELBW children
have an augmented urinary excretion of adrenal androgens, cortisol and
mineralocorticoid precursors. These findings corroborate and help to explain the
link between early-life adversity and subsequent adrenocortical function.
PMID- 26440940
TI - Fermi points and topological quantum phase transitions in a multi-band
superconductor.
AB - The importance of models with an exact solution for the study of materials with
non-trivial topological properties has been extensively demonstrated. The Kitaev
model plays a guiding role in the search for Majorana modes in condensed matter
systems. Also, the sp-chain with an anti-symmetric mixing among the s and p bands
is a paradigmatic example of a topological insulator with well understood
properties. Interestingly, these models share the same universality class for
their topological quantum phase transitions. In this work we study a two-band
model of spinless fermions with attractive inter-band interactions. We obtain its
zero temperature phase diagram, which presents a rich variety of phases including
a Weyl superconductor and a topological insulator. The transition from the
topological to the trivial superconducting phase has critical exponents different
from those of Kitaev's model.
PMID- 26440942
TI - A Hierarchical Bayesian Model to Predict Self-Thinning Line for Chinese Fir in
Southern China.
AB - Self-thinning is a dynamic equilibrium between forest growth and mortality at
full site occupancy. Parameters of the self-thinning lines are often confounded
by differences across various stand and site conditions. For overcoming the
problem of hierarchical and repeated measures, we used hierarchical Bayesian
method to estimate the self-thinning line. The results showed that the self
thinning line for Chinese fir (Cunninghamia lanceolata (Lamb.)Hook.) plantations
was not sensitive to the initial planting density. The uncertainty of model
predictions was mostly due to within-subject variability. The simulation
precision of hierarchical Bayesian method was better than that of stochastic
frontier function (SFF). Hierarchical Bayesian method provided a reasonable
explanation of the impact of other variables (site quality, soil type, aspect,
etc.) on self-thinning line, which gave us the posterior distribution of
parameters of self-thinning line. The research of self-thinning relationship
could be benefit from the use of hierarchical Bayesian method.
PMID- 26440941
TI - MDM2 Inhibitor, Nutlin 3a, Induces p53 Dependent Autophagy in Acute Leukemia by
AMP Kinase Activation.
AB - MDM2 (mouse double minute 2) inhibitors that activate p53 and induce apoptosis in
a non-genotoxic manner are in clinical development for treatment of leukemias.
P53 can modulate other programmed cell death pathways including autophagy both
transcriptionally and non-transcriptionally. We investigated autophagy induction
in acute leukemia by Nutlin 3a, a first-in-class MDM2 inhibitor. Nutlin 3a
induced autophagy in a p53 dependent manner and transcriptional activation of AMP
kinase (AMPK) is critical, as this effect is abrogated in AMPK -/- mouse
embryonic fibroblasts. Nutlin 3a induced autophagy appears to be pro-apoptotic as
pharmacological (bafilomycin) or genetic inhibition (BECLIN1 knockdown) of
autophagy impairs apoptosis induced by Nutlin 3a.
PMID- 26440943
TI - The Health Effects of Passive Smoking: An Overview of Systematic Reviews Based on
Observational Epidemiological Evidence.
AB - PURPOSE: We aim to systematically summarize the available epidemiological
evidence to identify the impact of environmental tobacco smoke on health.
METHODS: A systematic literature search of PubMed, Embase, Web of Science, and
Scopus for meta-analyses was conducted through January 2015. We included
systematic reviews that investigated the association between passive smoking and
certain diseases. Quantitative outcomes of association between passive smoking
and the risk of certain diseases were summarized. RESULTS: Sixteen meta-analyses
covering 130 cohort studies, 159 case-control studies, and 161 cross-sectional
studies and involving 25 diseases or health problems were reviewed. Passive
smoking appears not to be significantly associated with eight diseases or health
problems, but significantly elevates the risk for eleven specific diseases or
health problems, including invasive meningococcal disease in children (OR 2.18;
95% CI 1.63-2.92), cervical cancer (OR 1.73; 95% CI 1.35-2.21), Neisseria
meningitidis carriage (OR 1.68; 95% CI 1.19-2.36), Streptococcus pneumoniae
carriage (OR 1.66; 95% CI 1.33-2.07), lower respiratory infections in infancy (OR
1.42; 95% CI 1.33-1.51), food allergy (OR 1.43; 95% CI 1.12-1.83), and so on.
CONCLUSIONS: Our overview of systematic reviews of observational epidemiological
evidence suggests that passive smoking is significantly associated with an
increasing risk of many diseases or health problems, especially diseases in
children and cancers.
PMID- 26440944
TI - [A study of men born in 1913 show the art of becoming 100 years. Nonsmoking,
moderate coffee consumption and good income helps].
PMID- 26440945
TI - [Psychiatry and psychology integrated in somatics is a profit for the clinic.
Consultation liaison psychiatry important for the future of healthcare].
AB - The mental health needs of patients receiving physical health care often remain
undiagnosed and untreated, resulting in significant costs to the health care
system. However, some countries have recently seen fast progress with the
development of consultation liaison psychiatry. In Sweden, this service has
developed quite slowly, but a breakthrough may be imminent. There is evidence
that providing better support for co-morbid health problems may improve the
psychological quality of care and reduce physical health care costs in acute
hospitals. Consultation liaison psychiatry fits well with the current trends of
value-based health care, personalized care, and an emphasis on networking in
care.
PMID- 26440947
TI - [A unique collection of fetuses in jars. Tornbladinstitutet--living history of
medicine].
PMID- 26440946
TI - [Longer waiting time and higher mortality in older people with traumatic brain
injuries. Mapping of emergency prehospital management and hospital management in
Vasterbotten].
AB - The main purpose was to study the prehospital and early intrahospital treatment
of patients with traumatic brain injury (TBI) in the county of Vasterbotten 2011
2012. In total, 162 patients were included. The main finding was that a large
proportion of TBI patients were older men who fell in the same or from a
different level. Older patients had higher mortality and had to wait longer for
diagnostic imaging compared to younger patients. Furthermore, most patients were
initially relatively unaffected by the injury and around 1/5 of the patients were
transported to hospital by private transport. Finally, we observed that most
patients were admitted to hospital and computer tomography scan of the head was
performed within 4 hours.
PMID- 26440948
TI - [E-prescriptions should not govern physicians and pharmacists].
PMID- 26440949
TI - [Recent study shows iodine deficiency among pregnant women in Sweden].
PMID- 26440950
TI - [Wake up SALAR, the wheel is already invented!].
PMID- 26440951
TI - [Medical research and man broken into pieces].
PMID- 26440952
TI - [Higher mortality related to cannabis than to alcohol among young people].
PMID- 26440954
TI - [In Process Citation].
PMID- 26440953
TI - [In Process Citation].
PMID- 26440955
TI - [Despite the traffic barrier].
PMID- 26440956
TI - [The project has a wider purpose].
PMID- 26440957
TI - [2015 Nobel Prize in Physiology or Medicine. Better health for millions of people
thanks to drugs against parasites].
PMID- 26440958
TI - Balloon dilatation in patients with gastric outlet obstruction related to peptic
ulcer disease.
AB - BACKGROUND AND STUDY AIMS: Gastric outlet obstruction (GOO) is a rare
complication of peptic ulcer disease (PUD). The endoscopic balloon dilatation
(EBD) associated with medical treatment of Helicobacter pylori is a successful
method in the management of pyloric stenosis. The aim of this study was to
describe epidemiological, clinical, and endoscopic characteristics of GOO related
to PUD and to evaluate the effectiveness, safety, and outcome of EBD. PATIENTS
AND METHODS: In a retrospective study of patients seen between 1999 and 2009 with
symptoms of GOO secondary to PUD, pyloro-bulbar stenosis was confirmed by
endoscopic examination. Balloon dilatation was performed when obstruction
persisted after treatment with double-dose proton-pump inhibitor (PPI)
intravenously for 7-10days. The H. pylori status was assessed with histology, and
eradication therapy was prescribed for infection. RESULTS: A total of 45
consecutive patients (38 males, 7 females median age, 51.9years; range, 20
58years) with symptoms of GOO secondary to PUD underwent EBD. Median follow-up
time of the 45 patients was 32months (range, 4-126months). The immediate success
rate of the procedure was 95.5%. Clinical remission was noted in 84.4% of the
patients. Remission without relapse was observed in 55.8%, 30months after the
dilatation. Pyloric stenosis relapsed in 15 patients (39.5%) after a median
period of 22.9months. The dilatation was complicated in three patients (6.7%, two
perforations and one bleeding). A total of 13 patients (29%) underwent surgery.
H. pylori was found to be positive in 97.7% of the patients, and was eradicated
in 78.4% of them. Smoking and failure of H. pylori eradication were associated
with the relapse of the stenosis. CONCLUSION: EBD is a simple, effective, and
safe therapy for the GOO related to PUD, producing short- and long-term
remission.
PMID- 26440963
TI - Impact of a Serious Videogame Designed for Flexible Insulin Therapy on the
Knowledge and Behaviors of Children with Type 1 Diabetes: The LUDIDIAB Pilot
Study.
AB - BACKGROUND: Flexible (or functional) insulin therapy method is a self-management
education approach for intensive insulin therapy in patients with type 1
diabetes. The serious game (or applied game) "L'Affaire Birman" ("Mr. Birman's
File") (available at www.gluciweb.com ) was specifically designed as an
educational tool for the flexible insulin therapy method. Its educational impact
was evaluated in children with type 1 diabetes. MATERIALS AND METHODS: This
prospective multicenter pilot study evaluated the effect of this videogame on the
therapeutic knowledge and behavior of children with type 1 diabetes. PedCarbQuiz
(PCQ) and Diabetes Self-Management Profile (DSMP) questionnaires were used before
(T0), immediately after (T1), and 6 months after (T2) the unstructured use of the
videogame. RESULTS: The 38 children enrolled in the study were 42% boys and 58%
girls; they had a mean age of 13.7 +/- 2.1 years old, a diabetes duration of 6.0
+/- 3.8 years, and hemoglobin A1c (HbA1c) levels of 8.5 +/- 1.4% (69.4 +/- 9.4
mmol/mol). The children connected to the game 3.3 +/- 2.8 times during this 6
month study. Their PCQ score increased from 31.6 +/- 4.9 at T0 to 36.0 +/- 4.0 at
T2 (P < 0.05). Two PCQ subscores also increased significantly: the insulin
titration score at T1 and T2 and the carbohydrate quantification score at T2.
Conversely, the DSMP score was not different at T0, T1, and T2 (59.1 +/- 9.9,
60.2 +/- 9.8, and 60.0 +/- 10.0, respectively), and HbA1c levels also remained
stable throughout the study (8.4 +/- 1.3%, 8.4 +/- 1.2%, and 8.5 +/- 1.5% at T0,
T1, and T2, respectively). Subgroup analysis found a greater impact of the game
in children with poor glycemic control and low knowledge at baseline. Adherence
to the game was rather low (half of the children played less than 2.5 bouts), but
no criterion was found to be predictive of this low attractiveness. CONCLUSIONS:
Nonsupervised usage of the serious game "L'Affaire Birman" was able to improve
insulin titration and carbohydrate quantification in children with type 1
diabetes.
PMID- 26440964
TI - Effects of Hypoxia on the Physiology of Zebrafish (Danio rerio): Initial
Responses, Acclimation and Recovery.
AB - Hypoxia often occurs in aquatic environments as dissolved oxygen (DO)
concentration decrease to a level where it is detrimental to aquatic organisms.
To investigate the effects of hypoxia on the physiology of zebrafishes (Danio
rerio), the organisms were kept at normoxic conditions (DO: 8 +/- 0.3 mg L(-1):
control group) or were subjected to mild (DO: 3 +/- 0.3 mg L(-1)) or severe
hypoxia (DO: 1 +/- 0.2 mg L(-1)) for 48 h and a subsequent restoration of oxygen
concentrations (DO: 8 +/- 0.3 mg L(-1)) for another 96 h at 25 degrees C. We
found that the enzyme activities show different initial responses, acclimation
and recovery to severe hypoxia relative to normoxic conditions, but no
significant difference was observed between normoxic conditions and mild hypoxia.
The results suggest that zebrafishes can acclimate to the mild hypoxia (3 mg L(
1)) quickly but oxidative damage would occur when DO decreased below 1 mg L(-1).
Our findings could be useful for water resource managers to set protection limits
of DO for aquatic organisms.
PMID- 26440965
TI - High yield expression of novel glutaminase free L-asparaginase II of
Pectobacterium carotovorum MTCC 1428 in Bacillus subtilis WB800N.
AB - Gene encoding glutaminase-free L-asparaginase II (ans B2) from Pectobacterium
carotovorum MTCC 1428 was cloned into pHT43, transformed in Bacillus subtilis
WB800N and optimised the expression levels of recombinant enzyme. A three-fold
higher enzyme production was observed with an efficient transformant as compared
to native strain. Enzyme localization studies revealed that >90% of recombinant
enzyme is secreted extracellularly, a little fraction is attached to the membrane
(>6%) and localised intracellularly (3%). The expression of recombinant L
asparaginase II was confirmed by SDS-PAGE, IMAC (Immobilised metal ion affinity
chromatography) purification followed by Western blotting. Process parameter
optimization with OFAT (one factor at a time) revealed that rpm (120),
temperature (37 degrees C), Isopropyl beta-D-1-thiogalactopyranoside (IPTG)
concentration (1 mM) and time of induction (0.8 OD600nm) plays a vital role where
a maximum of 55 IU/ml was achieved. Further, consecutive induction by IPTG
improved the enzyme production up to 105 IU/ml with a specific activity of 101
IU/mg of protein. Molecular modelling analysis depicted that amino acids, GLY60,
GLY119 and ALA252 in the active site are responsible for the glutaminase free L
asparaginase II activity. This is the first report on enhanced expression of
recombinant glutaminase-free L-asparaginase II by intermediate addition of IPTG.
PMID- 26440966
TI - Impact of apoptosis on the on-line measured dielectric properties of CHO cells.
AB - Apoptosis is a common type of cell death in biopharmaceutical cell culture
processes which causes decrease in viable cell density and product yield. The
progression of apoptosis has been reported to influence the dielectric properties
of mammalian cells; however, the on-line detection of these effects has been
rarely described. This study provides a comprehensive analysis of the on-line
detectability of dielectric changes upon apoptosis induction in an industrial fed
batch process of CHO cells expressing a recombinant monoclonal antibody. Using
capacitance signals, measured at 25 frequencies, the impact of apoptosis on the
dielectric spectra was investigated in eight bioreactor cultivations in which
various process conditions were combined with two different apoptosis induction
strategies (camptothecin treatment and glucose starvation). To differentiate the
apoptosis-related information from the cell concentration-associated variance in
the multivariate capacitance datasets, principal component analysis (PCA) was
used. A second principal component, explaining an explicit proportion (>20%) of
the variance, was identified to be related to dielectric changes induced by
apoptosis. Furthermore, the analysis of caspase-3 and -7 activation and DNA
fragmentation showed that the detected dielectric change occurred in the early
phase of apoptosis. The presented results verify that apoptosis has a
considerable impact on the dielectric features of CHO cells and it can be
monitored on-line with the introduced tool-set combining capacitance measurement
with multivariate data analysis.
PMID- 26440968
TI - Hydrophobic pocket targeting probes for enteroviruses.
AB - Visualization and tracking of viruses without compromising their functionality is
crucial in order to understand virus targeting to cells and tissues, and to
understand the subsequent subcellular steps leading to virus uncoating and
replication. Enteroviruses are important human pathogens causing a vast number of
acute infections, and are also suggested to contribute to the development of
chronic diseases like type I diabetes. Here, we demonstrate a novel method to
target site-specifically the hydrophobic pocket of enteroviruses. A probe, a
derivative of Pleconaril, was developed and conjugated to various labels that
enabled the visualization of enteroviruses under light and electron microscopes.
The probe mildly stabilized the virus particle by increasing the melting
temperature by 1-3 degrees, and caused a delay in the uncoating of the virus in
the cellular endosomes, but could not however inhibit the receptor binding,
cellular entry or infectivity of the virus. The hydrophobic pocket binding moiety
of the probe was shown to bind to echovirus 1 particle by STD and tr-NOESY NMR
methods. Furthermore, binding to echovirus 1 and Coxsackievirus A9, and to a
lesser extent to Coxsackie virus B3 was verified by using a gold nanocluster
labeled probe by TEM analysis. Molecular modelling suggested that the probe fits
the hydrophobic pockets of EV1 and CVA9, but not of CVB3 as expected, correlating
well with the variations in the infectivity and stability of the virus particles.
EV1 conjugated to the fluorescent dye labeled probe was efficiently internalized
into the cells. The virus-fluorescent probe conjugate accumulated in the
cytoplasmic endosomes and caused infection starting from 6 hours onwards.
Remarkably, before and during the time of replication, the fluorescent probe was
seen to leak from the virus-positive endosomes and thus separate from the capsid
proteins that were left in the endosomes. These results suggest that, like the
physiological hydrophobic content, the probe may be released upon virus
uncoating. Our results collectively thus show that the gold and fluorescently
labeled probes may be used to track and visualize the studied enteroviruses
during the early phases of infection opening new avenues to follow virus
uncoating in cells.
PMID- 26440967
TI - Permethrin-Treated Clothing as Protection against the Dengue Vector, Aedes
aegypti: Extent and Duration of Protection.
AB - INTRODUCTION: Dengue transmission by the mosquito vector, Aedes aegypti, occurs
indoors and outdoors during the day. Personal protection of individuals,
particularly when outside, is challenging. Here we assess the efficacy and
durability of different types of insecticide-treated clothing on laboratory
reared Ae. aegypti. METHODS: Standardised World Health Organisation Pesticide
Evaluation Scheme (WHOPES) cone tests and arm-in-cage assays were used to assess
knockdown (KD) and mortality of Ae. aegypti tested against factory-treated
fabric, home-dipped fabric and microencapsulated fabric. Based on the testing of
these three different treatment types, the most protective was selected for
further analysis using arm-in cage assays with the effect of washing, ultra
violet light, and ironing investigated using high pressure liquid chromatography.
RESULTS: Efficacy varied between the microencapsulated and factory dipped fabrics
in cone testing. Factory-dipped clothing showed the greatest effect on KD (3 min
38.1%; 1 hour 96.5%) and mortality (97.1%) with no significant difference between
this and the factory dipped school uniforms. Factory-dipped clothing was
therefore selected for further testing. Factory dipped clothing provided 59% (95%
CI = 49.2%- 66.9%) reduction in landing and a 100% reduction in biting in arm-in
cage tests. Washing duration and technique had a significant effect, with
insecticidal longevity shown to be greater with machine washing (LW50 = 33.4)
compared to simulated hand washing (LW50 = 17.6). Ironing significantly reduced
permethrin content after 1 week of simulated use, with a 96.7% decrease after 3
months although UV exposure did not reduce permethrin content within clothing
significantly after 3 months simulated use. CONCLUSION: Permethrin-treated
clothing may be a promising intervention in reducing dengue transmission.
However, our findings also suggest that clothing may provide only short-term
protection due to the effect of washing and ironing, highlighting the need for
improved fabric treatment techniques.
PMID- 26440969
TI - Serial investigation of PTPN11 mutation in nonhematopoietic tissues in a patient
with juvenile myelomonocytic leukemia who was treated with unrelated cord blood
transplantation.
AB - After allogeneic stem-cell transplantation, nonhematopoietic tissues contain
donor-derived cells; however, whether cells from malignant hematological disease
can also be found in nonhematopoietic tissues is unclear. This report describes a
juvenile myelomonocytic leukemia (JMML) case with a typical PTPN11 mutation
(p.E76K) at different allele frequencies in the bone marrow mononuclear cells,
buccal smear cells, and fingernails at diagnosis, which was suggestive of PTPN11
somatic mosaicism; however, the PTPN11 mutation in the buccal smear cells and
fingernails was lost after unrelated cord blood transplantation. These results
suggest that JMML-derived cells may migrate into and reside in nonhematopoietic
tissues and furthermore that these cells can be eradicated by cord blood
transplantation.
PMID- 26440970
TI - Outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation
for multiple myeloma.
AB - We retrospectively evaluated single-institute outcomes of allogeneic
hematopoietic stem cell transplantation (allo-HSCT) with a reduced-intensity
conditioning regimen consisting of fludarabine (125 mg/m2) and melphalan (140
mg/m2) for multiple myeloma. Twenty-three patients (median age: 46 years) were
evaluated. Stem cell sources were bone marrow or peripheral blood stem cells from
siblings (n = 4) and bone marrow from unrelated donors (n = 19). For graft-versus
host disease prophylaxis, cyclosporine A or tacrolimus with short-term
methotrexate was given. Disease status at time of transplant was complete
response in four patients, very good partial or partial response in 13, and
stable or progressive disease in six. The median follow-up period of 7 survivors
at analysis was 73.2 months (range 46.0-158.9 months). During the follow-up,
disease recurrence or progression was observed in 21 patients, and was primary
causes of death in 88% of the patients. The 5-year overall survival and
progression-free survival rates were 38.6% (95% CI 19.3-57.7%) and 5.4% (95% CI
0.4-21.6%), respectively. Although allo-HSCT with this conditioning could be
safely performed, further refinement of this approach aiming at more effective
eradication of myeloma cells is clearly warranted.
PMID- 26440971
TI - Absolute lymphocyte count at the end of induction therapy is a prognostic factor
in childhood acute lymphoblastic leukemia.
AB - Recent studies have reported that the absolute lymphocyte count (ALC) during
induction therapy is predictive of treatment outcome in de novo acute
lymphoblastic leukemia (ALL); however, the significance of ALC on outcomes
remains controversial. In the present study, we assessed the significance of ALC
at day 29 (ALC-29), the end of induction therapy, on outcomes in our Japanese
cohort. The outcomes of 141 patients aged <=18 years with newly diagnosed ALL who
were enrolled on the JACLS ALL-02 at our hospitals were analyzed in terms of ALC
29. Patients with ALC-29 >=750/MUL (n = 81) had a superior 5-year EFS (95.2 +/-
2.7 vs 84.3 +/- 4.8 %, P = 0.016) and OS (100 vs 87.0 +/- 4.7 %, P = 0.0062). A
multivariate analysis identified ALC-29 >=750/MUL as a significant predictor of
improved EFS and OS after controlling for confounding factors. A multiple linear
regression model revealed a significant inverse relationship between the
percentage of blasts in bone marrow on day 15 and ALC-29 (P = 0.005). These
results indicate that ALC is a simple prognostic factor in childhood ALL, and,
thus, has the potential to refine current risk algorithms.
PMID- 26440972
TI - Aging, clonal hematopoiesis and preleukemia: not just bad luck?
AB - Chronological human aging is associated with a number of changes in the
hematopoietic system, occurring at many levels from stem to mature cells, and the
marrow microenvironment as well. This review will focus mainly on the aging of
hematopoietic stem and progenitor cells (HSPCs), and on the associated increases
in the incidence of hematological malignancies. HSPCs manifest reduced function
and acquire molecular changes with chronological aging. Furthermore, while for
many years it has been known that the human hematopoietic system becomes
increasingly clonal with chronological aging (clonal hematopoiesis), only in the
last few years has it become clear that clonal hematopoiesis may result from the
accumulation of preleukemic mutations in HSPCs. Such mutations confer a selective
advantage that leads to clonal hematopoiesis, and that may occasionally result in
the development of leukemia, and define the existence of both preleukemic stem
cells, and of 'preleukemia' as a clinical entity. While it is well appreciated
that clonal hematopoiesis is very common in the elderly, several questions remain
unanswered: why and how does clonal hematopoiesis develop? How is clonal
hematopoiesis related to the age-related changes observed in the hematopoietic
system? And why do only some individuals with clonal hematopoiesis develop
leukemia?
PMID- 26440973
TI - Bleeding complications in BCR-ABL negative myeloproliferative neoplasms:
prevalence, type, and risk factors in a single-center cohort.
AB - The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk
of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less
well defined than those for thrombosis. Because patients with CALR mutations have
higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates
may be increased in this group. Our aim was to retrospectively evaluate whether
acquired von Willebrand disease (AvWD), thrombocytosis, mutational status, or
treatment history are associated with bleeding in a cohort of MPN patients. Using
an electronic database, MPN patients seen between 2005 and 2013 were
retrospectively identified using ICD-9 codes and billing records. A bleeding
event was defined as one that was identified in the medical record and graded
based on the Common Terminology Criteria for Adverse Event (CTCAE) version 4.0.
Among 351 MPN patients, 15.6 % experienced 64 bleeding event types. There was no
association of bleeding with mutational status, gender, MPN subtype, aspirin use,
prior thrombosis, or platelet count at presentation. There was an association
between bleeding and older age at diagnosis. aVWD was identified in six patients.
In this single-center retrospective study, bleeding events were identified in 15
% of patients, and associated with older age at diagnosis. aVWD was rarely tested
for in this cohort.
PMID- 26440974
TI - Microarray CGH analysis of hematological patients with del(20q).
AB - Deletion of the long arm of chromosome 20 is a common abnormality underlying
hematological malignancy. We analyzed 21 patients with hematologic diseases
confirmed to carry the del(20q) by conventional cytogenetics and fluorescence in
situ hybridization using microarray comparative genomic hybridization (aCGH).
Seventeen patients were positive for del(20q), but this deletion was not detected
in four patients. All deletions detected were interstitial of which continuous
deletions were seen in 12 patients and discrete deletions in five. Three commonly
deleted regions (CDRs) and two commonly retained regions (CRRs) were defined:
CDR1 spanning 3.05Mb (34560497-37608229) within 20q11.23, CDR2 spanning 1.76Mb
(37851501-39615698) within 20q12, CDR3 spanning 116Kb (48120412-48236791) within
20q13.13, CRR1 spanning 1.1Mb (29374726-30428250) within 20q11.21, and CRR2
spanning 2.5Mb (60484668-62963548) within 20q13.33. Duplications of retained
regions (20q11.21) were found in five cases with similar erythroid hyperplasia (2
M6, 3 MDS). Moreover, duplication of 20p13-p11.21 was also found in two cases
with M6. Using the CDRs and CRRs, we identified the candidate genes we searched
for using the UCSC Genome Browser. Our data suggest that aCGH analysis is useful
for more precisely defining breakpoints on 20q. Further work is required to
identify candidate pathogenic genes within these CDRs and CRRs.
PMID- 26440975
TI - Impairment of hematopoietic stem cell niches in patients with aplastic anemia.
AB - Aplastic anemia (AA) is a serious hematological disorder characterized by
pancytopenia and defective bone marrow (BM) microenvironment. Previous
investigations have demonstrated that there is a defect of angiogenesis in the BM
of patients with AA. However, whether abnormalities of the BM microenvironment,
particularly the overall specialization of niches, which have been classified
into osteoblastic, vascular, and perivascular niches, are involved in the
pathogenesis of AA is unknown. In the present study, 46 patients with AA and 15
controls were selected. The cellular elements of the BM microenvironment,
including endosteal, vascular, and perivascular cells, were analyzed by
immunohistochemical staining in situ. Patients with AA showed markedly fewer
endosteal cells [0.33 vs 3.67 per high-power field (hpf); P < 0.05], vascular
cells (8.00 vs 12.67 per hpf; P < 0.05), and perivascular cells (7.17 vs 10.67
per hpf; P < 0.05) compared with controls. These data indicate that AA is
associated with impaired hematopoietic stem cell niches.
PMID- 26440976
TI - Bilateral psoas muscle lymphoma: an unusual presentation of EBV-positive diffuse
large B-cell lymphoma of the elderly.
PMID- 26440977
TI - Integrin beta-3 genetic variants and risk of venous thromboembolism in colorectal
cancer patients.
AB - BACKGROUND: Integrin beta3 is involved in tumor and endothelial cell biology as
well as in platelet aggregation. Herein, we evaluated the predictive potential of
three germline single nucleotide polymorphisms (SNPs) in the integrin beta3 gene
(rs3809865, rs5918 and rs4642) to predict the risk of venous thromboembolism
(VTE) in colorectal cancer (CRC) patients, which is one of the leading causes of
death among cancer patients. METHODS: 112 patients diagnosed with CRC enrolled in
the prospective Vienna Cancer and Thrombosis Study (CATS) were assessed with a
median follow-up of 46 months. DNA was isolated from venous blood samples and
SNPs were analyzed by the PCR-RFLP method. RESULTS: VTE occurred in 12% (n=13) of
all patients. The SNPs rs5918 and rs4642 were not associated with VTE risk. For
rs3809565, 23% (n=11) of patients had the A/A genotype, 4% (n=2) had the A/T
genotype, but none (0%) had the T/T genotype. In the univariate analysis,
patients with the A/A genotype had a significantly higher risk to develop VTE
compared to the other polymorphisms (P=0.0005 after Fine and Gray). In the
multivariable analysis, the predictive value remained significant. CONCLUSIONS:
This study identified the rs3809865 A/A genotype as an independent risk factor
for VTE in CRC patients. Our findings would help identify high risk patients and
would be essential for tailored anticoagulant prophylaxis.
PMID- 26440978
TI - The Impact of Tic Severity, Comorbidity and Peer Attachment on Quality of Life
Outcomes and Functioning in Tourette's Syndrome: Parental Perspectives.
AB - The aim of this controlled, community-based study based on data from parents of
youth (aged 7-16 years) with Tourette's syndrome (TS; n = 86) and parents of age
and gender matched peers (n = 108) was to test several hypotheses involving a
range of variables salient to the TS population, including peer attachment,
quality of life, severity of tics, comorbidity, and psychological, behavioural
and social dysfunction. Multivariate between-group analyses confirmed that TS
group youth experienced lower quality of life, increased emotional, behavioural
and social difficulties, and elevated rates of insecure peer attachment relative
to controls, as reported by their primary caregiver. Results also confirmed the
main hypothesis that security of peer attachment would be associated with
individual variability in outcomes for youth with TS. As predicted, multivariate
within-TS group analyses determined strong relationships among adverse quality of
life outcomes and insecure attachment to peers, increased tic severity, and the
presence of comorbid disorder. Findings suggest that youth with TS are at
increased risk for insecure peer attachment and that this might be an important
variable impacting the quality of life outcomes for those diagnosed.
PMID- 26440979
TI - "Vision for Action" in Young Children Aligning Multi-Featured Objects:
Development and Comparison with Nonhuman Primates.
AB - Effective vision for action and effective management of concurrent spatial
relations underlie skillful manipulation of objects, including hand tools, in
humans. Children's performance in object insertion tasks (fitting tasks) provides
one index of the striking changes in the development of vision for action in
early life. Fitting tasks also tap children's ability to work with more than one
feature of an object concurrently. We examine young children's performance on
fitting tasks in two and three dimensions and compare their performance with the
previously reported performance of adult individuals of two species of nonhuman
primates on similar tasks. Two, three, and four year-old children routinely
aligned a bar-shaped stick and a cross-shaped stick but had difficulty aligning a
tomahawk-shaped stick to a matching cut-out. Two year-olds were especially
challenged by the tomahawk. Three and four year-olds occasionally held the stick
several inches above the surface, comparing the stick to the surface visually,
while trying to align it. The findings suggest asynchronous development in the
ability to use vision to achieve alignment and to work with two and three spatial
features concurrently. Using vision to align objects precisely to other objects
and managing more than one spatial relation between an object and a surface are
already more elaborated in two year-old humans than in other primates. The human
advantage in using hand tools derives in part from this fundamental difference in
the relation between vision and action between humans and other primates.
PMID- 26440980
TI - Oxidation of Ni-ECp* Complexes: Stable Open-Shell Ni(I) Cations
[Ni(ECp*)n(PPh3)(4-n)](+) (n = 2, 4; E = Al, Ga).
AB - Uncommon Ni(I) cationic complexes were synthesized by treating [Ni(ECp*)2(PPh3)2]
(E = Al, Ga; Cp* = pentamethylcyclopentadienyl) with 1 equiv of [FeCp2][BAr4(F)].
All compounds have been prepared readily in high yield. The paramagnetic
compounds were characterized by single-crystal X-ray crystallography, mass
spectrometry, elemental analysis, magnetic susceptibility, and electron
paramagnetic resonance spectroscopy.
PMID- 26440982
TI - Hypertension: PATHWAY to improving the treatment of drug-resistant hypertension.
PMID- 26440981
TI - Biomarkers: Troponin testing--risk stratification to stratified medicine.
AB - Among patients with diabetes mellitus and ischaemic heart disease, high
sensitivity testing effectively identified 39.3% of patients with elevated
troponin levels who were at high 5-year risk of cardiovascular death, myocardial
infarction, or stroke. Compared with optimal medical therapy, revascularization
did not reduce ischaemic events among patients with elevated troponin levels.
PMID- 26440983
TI - Constrictive pericarditis--a curable diastolic heart failure.
PMID- 26440984
TI - Important role of myocardial tissue characterization by cardiac MRI in diagnosing
Takotsubo syndrome.
PMID- 26440985
TI - Valvular disease: Importance of balloon valvuloplasty before TAVI to prevent
embolization.
PMID- 26440986
TI - Use of cardiac MRI to diagnose Takotsubo syndrome.
PMID- 26440987
TI - Risk factors: Alcohol intake, MI, and income level.
PMID- 26440992
TI - Bronchoconstriction induced by inhaled methacholine delays desflurane uptake and
elimination in a piglet model.
AB - Bronchoconstriction is a hallmark of asthma and impairs gas exchange. We
hypothesized that pharmacokinetics of volatile anesthetics would be affected by
bronchoconstriction. Ventilation/perfusion (VA/Q) ratios and pharmacokinetics of
desflurane in both healthy state and during inhalational administration of
methacholine (MCh) to double peak airway pressure were studied in a piglet model.
In piglets, MCh administration by inhalation (100 MUg/ml, n=6) increased
respiratory resistance, impaired VA/Q distribution, increased shunt, and
decreased paO2 in all animals. The uptake and elimination of desflurane in
arterial blood was delayed by nebulization of MCh, as determined by Micropore
Membrane Inlet Mass Spectrometry (wash-in time to P50, healthy vs. inhalation:
0.5 min vs. 1.1 min, to P90: 4.0 min vs. 14.8 min). Volatile elimination was
accordingly delayed. Inhaled methacholine induced severe bronchoconstriction and
marked inhomogeneous VA/Q distribution in pigs, which is similar to findings in
human asthma exacerbation. Furthermore, MCh-induced bronchoconstriction delayed
both uptake and elimination of desflurane. These findings might be considered
when administering inhalational anesthesia to asthmatic patients.
PMID- 26440993
TI - Epidemiology of severe trauma in Spain. Registry of trauma in the ICU (RETRAUCI).
Pilot phase.
AB - OBJECTIVE: To describe the characteristics and management of severe trauma
disease in Spanish Intensive Care Units (ICUs). Registry of trauma in the ICU
(RETRAUCI). Pilot phase. DESIGN: A prospective, multicenter registry. SETTING:
Thirteen Spanish ICUs. PATIENTS: Patients with trauma disease admitted to the
ICU. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Epidemiology, out-of
hospital attention, registry of injuries, resources utilization, complications
and outcome were evaluated. RESULTS: Patients, n=2242. Mean age 47.1+/-19.02
years. Males 79%. Blunt trauma 93.9%. Injury Severity Score 22.2+/-12.1, Revised
Trauma Score 6.7+/-1.6. Non-intentional in 84.4% of the cases. The most common
causes of trauma were traffic accidents followed by pedestrian and high-energy
falls. Up to 12.4% were taking antiplatelet medication or anticoagulants. Almost
28% had a suspected or confirmed toxic influence in trauma. Up to 31.5% required
an out-of-hospital artificial airway. The time from trauma to ICU admission was
4.7+/-5.3hours. At ICU admission, 68.5% were hemodynamically stable. Brain and
chest injuries predominated. A large number of complications were documented.
Mechanical ventilation was used in 69.5% of the patients (mean 8.2+/-9.9 days),
of which 24.9% finally required a tracheostomy. The median duration of stay in
the ICU and in hospital was 5 (range 3-13) and 9 (5-19) days, respectively. The
ICU mortality rate was 12.3%, while the in-hospital mortality rate was 16.0%.
CONCLUSIONS: The pilot phase of the RETRAUCI offers a first impression of the
epidemiology and management of trauma disease in Spanish ICUs.
PMID- 26440994
TI - [Forty years since description of the Kirby index (PaO2/FiO2)].
PMID- 26440995
TI - Stereoselective [3+2] Carbocyclization of Indole-Derived Imines and Electron-Rich
Alkenes: A Divergent Synthesis of Cyclopenta[b]indole or Tetrahydroquinoline
Derivatives.
AB - An unprecedented stereoselective [3+2] carbocyclization reaction of indole-2
carboxaldehydes, anilines, and electron-rich alkenes to obtain
cyclopenta[b]indoles is disclosed. This pathway is different from the well
established Povarov reaction: the formal [4+2] cycloaddition involving the same
components, which affords tetrahydroquinolines. Moreover, by simply changing the
Bronsted acid catalyst, this multicomponent coupling process could be divergently
directed towards the conventional Povarov pathway to produce tetrahydroquinolines
or to the new pathway (anti-Povarov) to generate cyclopenta[b]indoles. Supported
by computational studies, a stepwise Mannich/Friedel-Crafts cascade is proposed
for the new anti-Povarov reaction, whereas a concerted [4+2] cycloaddition
mechanism is proposed for the Povarov reaction.
PMID- 26440996
TI - Crystal structure of quinone-dependent alcohol dehydrogenase from
Pseudogluconobacter saccharoketogenes. A versatile dehydrogenase oxidizing
alcohols and carbohydrates.
AB - The quinone-dependent alcohol dehydrogenase (PQQ-ADH, E.C. 1.1.5.2) from the Gram
negative bacterium Pseudogluconobacter saccharoketogenes IFO 14464 oxidizes
primary alcohols (e.g. ethanol, butanol), secondary alcohols (monosaccharides),
as well as aldehydes, polysaccharides, and cyclodextrins. The recombinant
protein, expressed in Pichia pastoris, was crystallized, and three-dimensional
(3D) structures of the native form, with PQQ and a Ca(2+) ion, and of the enzyme
in complex with a Zn(2+) ion and a bound substrate mimic were determined at 1.72
A and 1.84 A resolution, respectively. PQQ-ADH displays an eight-bladed beta
propeller fold, characteristic of Type I quinone-dependent methanol
dehydrogenases. However, three of the four ligands of the Ca(2+) ion differ from
those of related dehydrogenases and they come from different parts of the
polypeptide chain. These differences result in a more open, easily accessible
active site, which explains why PQQ-ADH can oxidize a broad range of substrates.
The bound substrate mimic suggests Asp333 as the catalytic base. Remarkably, no
vicinal disulfide bridge is present near the PQQ, which in other PQQ-dependent
alcohol dehydrogenases has been proposed to be necessary for electron transfer.
Instead an associated cytochrome c can approach the PQQ for direct electron
transfer.
PMID- 26440997
TI - Postnatal nicotine effects on the expression of nicotinic acetylcholine receptors
in the developing piglet hippocampus and brainstem.
AB - Postnatal exposure to cigarette smoke during infancy is associated with increased
number of respiratory illnesses, impaired pulmonary function, and the occurrence
of Sudden Infant Death Syndrome (SIDS). It is also associated with reduced
cognitive functioning and attention deficits in childhood. Nicotine, the major
neurotoxic component of cigarette smoke, induces its actions by binding to
nicotinic acetylcholine receptors (nAChR). Using a piglet model of postnatal
nicotine exposure, we studied the immunohistochemical expression of nAChR
subunits alpha2, alpha3, alpha4, alpha5, alpha7, alpha9, beta1 and beta2 in the
brainstem medulla and the hippocampus, given the role of these structures in
cardiorespiratory control and cognition, respectively. We compared piglets
exposed postnatally to 2mg/kg/day nicotine for 14 days (n=14: 7 males: 7 females)
to controls (n=14: 7 males: 7 females). In the hippocampus, decreased expression
was seen for alpha3 in CA1 (p=0.017), alpha9 in CA1 (p<0.001) and CA2 (p<0.001),
beta1 in CA1 (p=0.001) and CA2 (p=0.001) and beta2 in CA3 (p=0.036). In the
medulla, the nucleus of the spinal trigeminal tract had increased alpha2 and
alpha4; vestibular nucleus increased alpha2 and alpha3, and decreased alpha4;
hypoglossal decreased alpha3 and beta1; dorsal motor nucleus of the vagus
decreased alpha4 and beta1. This is the first demonstration that non-classical
nAChR subunits are affected by postnatal nicotine in the developing brain, and
the implications are discussed.
PMID- 26440999
TI - Estimating the cost-effectiveness of daclatasvir plus asunaprevir in difficult to
treat Japanese patients chronically infected with hepatitis C genotype 1b.
AB - AIM: Standard of care for chronic hepatitis C in Japan is currently a pegylated
interferon (IFN)-alpha + ribavirin (PR)-based regimen, notably associated with
efficacy and tolerability issues. The advent of novel direct-acting antivirals
(DAA) has provided more efficacious and better tolerated treatments. This study
investigated the cost-effectiveness of the daclatasvir + asunaprevir (DCV + ASV)
DAA regimen in patients infected with hepatitis C virus (HCV) genotype 1b who had
previously not responded to or were ineligible for IFN-containing regimens.
METHODS: A cost-utility analysis using an established Markov model compared DCV +
ASV with simeprevir + PR (SMV + PR), telaprevir + PR (TVR + PR) and no treatment
using Japanese-specific model inputs, with costs and utility values discounted at
2%. A cohort of patients was simulated until death and predicted quality-adjusted
life-years (QALY) and costs were estimated. A subgroup analysis of patients with
no DCV resistance was conducted. RESULTS: In all scenarios, DCV + ASV was
predicted to be dominant over the comparator; namely, DCV + ASV was associated
with increased QALY gains and decreased cost. In patients treated during the
chronic hepatitis C stage, cost reductions were Y1 057 288-2 619 206, and in
patients treated during the compensated cirrhosis (CC) stage, reductions were Y1
032 224-2 531 930. QALY gains were 0.749-2.609 and 0.874-3.043, respectively.
Results improved when considering the subgroup of patients without DCV
resistance. CONCLUSION: Cost-effectiveness conclusions are similar for patients
treated in the chronic hepatitis C and CC disease stages, with DCV + ASV expected
to be cost-saving versus standard of care in Japan for patients with HCV genotype
1b patients who have failed prior therapy or are IFN-ineligible/intolerant.
PMID- 26440998
TI - Suppression of Dendritic Cell-Derived IL-12 by Endogenous Glucocorticoids Is
Protective in LPS-Induced Sepsis.
AB - Sepsis, an exaggerated systemic inflammatory response, remains a major medical
challenge. Both hyperinflammation and immunosuppression are implicated as causes
of morbidity and mortality. Dendritic cell (DC) loss has been observed in septic
patients and in experimental sepsis models, but the role of DCs in sepsis, and
the mechanisms and significance of DC loss, are poorly understood. Here, we
report that mice with selective deletion of the glucocorticoid receptor (GR) in
DCs (GR(CD11c-cre)) were highly susceptible to LPS-induced septic shock,
evidenced by elevated inflammatory cytokine production, hypothermia, and
mortality. Neutralizing anti-IL-12 antibodies prevented hypothermia and death,
demonstrating that endogenous GC-mediated suppression of IL-12 is protective. In
LPS-challenged GR(CD11c-cre) mice, CD8(+) DCs were identified as the major source
of prolonged IL-12 production, which correlated with elevations of NK cell
derived IFN-gamma. In addition, the loss of GR in CD11c(+) cells rescued LPS
induced loss of CD8(+) DCs but not other DC subsets. Unlike wild-type animals,
exposure of GR(CD11c-cre) mice to low-dose LPS did not induce CD8(+) DC loss or
tolerance to subsequent challenge with high dose, but neutralization of IL-12
restored the ability of low-dose LPS to tolerize. Therefore, endogenous
glucocorticoids blunt LPS-induced inflammation and promote tolerance by
suppressing DC IL-12 production.
PMID- 26441000
TI - Remote histology learning from static versus dynamic microscopic images.
AB - Histology is the study of microscopic structures in normal tissue sections.
Curriculum redesign in medicine has led to a decrease in the use of optical
microscopes during practical classes. Other imaging solutions have been
implemented to facilitate remote learning. With advancements in imaging
technologies, learning material can now be digitized. Digitized microscopy images
can be presented in either a static or dynamic format. This study of remote
histology education identifies whether dynamic pictures are superior to static
images for the acquisition of histological knowledge. Test results of two cohorts
of second-year Bachelor in Medicine students at Ghent University were analyzed in
two consecutive academic years: Cohort 1 (n = 190) and Cohort 2 (n = 174).
Students in Cohort 1 worked with static images whereas students in Cohort 2 were
presented with dynamic images. ANCOVA was applied to study differences in
microscopy performance scores between the two cohorts, taking into account any
possible initial differences in prior knowledge. The results show that practical
histology scores are significantly higher with dynamic images as compared to
static images (F (1,361) = 15.14, P < 0.01), regardless of student's gender and
performance level. Several reasons for this finding can be explained in
accordance with cognitivist learning theory. Since the findings suggest that
knowledge construction with dynamic pictures is stronger as compared to static
images, dynamic images should be introduced in a remote setting for microscopy
education. Further implementation within a larger electronic learning management
system needs to be explored in future research. Anat Sci Educ 9: 222-230. (c)
2015 American Association of Anatomists.
PMID- 26441001
TI - Structural and dynamical correlations in PfHGXPRT oligomers: A molecular dynamics
simulation study.
AB - PfHGXPRT is a key enzyme involved in purine nucleotide salvage pathway of the
malarial parasite, Plasmodium falciparum. Atomistic molecular dynamics
simulations have been performed on two types of PfHGXPRT dimers (D1 and D3) and
its tetramer in their apo and ligand-bound states. A significant event in the
catalytic cycle is the dynamics of a gate that provides access for the ligand
molecules to the reaction center. The gate is formed by loops II and IV, the
former being the most flexible. Large amplitude conformational changes have been
observed in active site loop II. Upon complete occupancy of the active site, loop
II gets stabilized due to specific interactions between its residues and the
ligand molecules. Remote loop, X, is seen to be less fluxional in the D3 dimer
than in D1 which is rationalized as due to the greater number of inter-subunit
contacts in the former. The presence of ligand molecules in subunits of the
tetramer further reduces the flexibility of loop X epitomizing a communication
between this region and the active sites in the tetramer. These observations are
in accordance with the outcomes of several experimental investigations.
Participation of loop X in the oligomerization process has also been discerned.
Between the two types of dimers in solution, D1 tetramerizes readily and thus
would not be present as free dimers. We conjecture an equilibrium to exist
between D3 and the tetramer in solution; upon binding of the ligand molecules to
the D3 dimer, this equilibrium shifts toward the tetramer.
PMID- 26441003
TI - Integration of DNA sequence and DNA methylation changes in monozygotic twin pairs
discordant for schizophrenia.
AB - Schizophrenia is a complex mental disorder with high heritability (80%),
extensive genetic heterogeneity, environmental contributions and only 50%
concordance in discordant monozygotic (MZ) twins. Discordant MZ twins provide an
exceptional opportunity to assess patient specific genome-wide genetic and
epigenetic changes that may account for the disease phenotype. A combined
analysis of genetic and epigenetic changes on the same twin pairs is expected to
provide a more effective approach for two reasons. First, it is now possible to
generate relatively reliable complete genome sequences as well as promoter
methylation states on an individual level and second, the unaffected twin that
originated from the same zygote provides a near perfect genetic match for
contrast and comparison. This report deals with the combined analysis of DNA
sequence data and methylation data on two pairs of discordant MZ twins that have
been clinically followed for over 20 years. Results on Family 1 show that 58
genes differ in DNA sequence as well as promoter methylation in a schizophrenia
affected twin as compared to her healthy co-twin. The corresponding number for
family 2 was 13. The two lists are over represented by neuronal genes and include
a number of known schizophrenia candidate genes and drug targets. The results
argue that changes in multiple genes via co-localized genetic and epigenetic
alteration contribute to a liability threshold that is necessary for development
of schizophrenia. This novel hypothesis, although logical, remains to be
validated.
PMID- 26441002
TI - Iridium-Catalyzed Enantioselective Allylic Substitution of Enol Silanes from
Vinylogous Esters and Amides.
AB - The enol silanes of vinylogous esters and amides are classic dienes for Diels
Alder reactions. Here, we report their reactivity as nucleophiles in Ir
catalyzed, enantioselective allylic substitution reactions. A variety of allylic
carbonates react with these nucleophiles to give allylated products in good
yields with high enantioselectivities and excellent branched-to-linear ratios.
These reactions occur with KF or alkoxide as the additive, but mechanistic
studies suggest that these additives do not activate the enol silanes. Instead,
they serve as bases to promote the cyclometalation to generate the active Ir
catalyst. The carbonate anion, which was generated from the oxidative addition of
the allylic carbonate, likely activates the enol silanes to trigger their
activity as nucleophiles for reactions with the allyliridium electrophile. The
synthetic utility of this method was illustrated by the synthesis of the anti
muscarinic drug, fesoterodine.
PMID- 26441004
TI - Severity of thought disorder predicts psychosis in persons at clinical high-risk.
AB - BACKGROUND: Improving predictive accuracy is of paramount importance for early
detection and prevention of psychosis. We sought a symptom severity classifier
that would improve psychosis risk prediction. METHODS: Subjects were from two
cohorts of the North American Prodrome Longitudinal Study. All subjects met
Criteria of Psychosis-Risk States. In Cohort-1 (n=296) we developed a classifier
that included those items of the Scale of Psychosis-Risk Symptoms that best
distinguished subjects who converted to psychosis from nonconverters, with
performance initially validated by randomization tests in Cohort-1. Cohort-2
(n=592) served as an independent test set. RESULTS: We derived 2-Item and 4-Item
subscales. Both included unusual thought content and suspiciousness; the latter
added reduced ideational richness and difficulties with focus/concentration. The
Concordance Index (C-Index), a measure of discrimination, was similar for each
subscale across cohorts (4-Item subscale Cohort-2: 0.71, 95% CI=[0.64, 0.77],
Cohort-1: 0.74, 95% CI=[0.69, 0.80]; 2-Item subscale Cohort-2: 0.68, 95% CI=[0.3,
0.76], Cohort-1: 0.72, 95% CI=[0.66-0.79]). The 4-Item performed better than the
2-Item subscale in 742/1000 random selections of 80% subsets of Cohort-2 subjects
(p-value=1.3E-55). Subscale calibration between cohorts was proportional (higher
scores/lower survival), but absolute conversion risk predicted from Cohort-1 was
higher than that observed in Cohort-2, reflecting the cohorts' differences in 2
year conversion rates (Cohort-2: 0.16, 95% CI=[0.13, 0.19]; Cohort-1: 0.30, 95%
CI=[0.24, 0.36]). CONCLUSION: Severity of unusual thought content,
suspiciousness, reduced ideational richness, and difficulty with
focus/concentration informed psychosis risk prediction. Scales based on these
symptoms may have utility in research and, assuming further validation, eventual
clinical applications.
PMID- 26441005
TI - The MATRICS Consensus Cognitive Battery (MCCB): Co-norming and standardization in
China.
AB - MATRICS Consensus Cognitive Battery (MCCB), packaging 10 tests selected from more
than 90 nominated tests, is a method developed by the Measurement and Treatment
Research to Improve Cognition in Schizophrenia (MATRICS) group to evaluate the
efficacy of treatments targeting cognitive impairments in schizophrenia. MCCB had
been translated into a number of languages, but only the US and Spain had
normative data reported. Inconsistency in translation and cultural differences
make direct application of MCCB in China problematic. In this study, we
administered the battery to a representative community sample based on Chinese
population census in 2005 and obtained normative data. The effects of age,
gender, education level, and scale of residence area on test performance were
examined. The sample included 656 healthy volunteers from six sites in China. At
each site, sample was stratified according to age, gender, and educational level,
and scale of the area one was born in, grew up in and currently living in was
recorded. We found age, gender, and education had significant effects on the
normative data for MCCB in China, which are comparable to those found for the
original standardized English version in the U.S. and the Spanish version in
Spain. Remarkably, the residence scale effects on neuropsychological performance
were significant, which should be taking into account when calculating the
standardized T score for each subject. The practice effects were minor and test
retest reliability of MCCB was good, which suggests MCCB as an appropriate
measure for clinical and research usage in China.
PMID- 26441006
TI - Dorsal striatal volumes in never-treated patients with first-episode
schizophrenia before and during acute treatment.
AB - BACKGROUND: Studies of pre-and post-treatment striatal volume in schizophrenia
have reported conflicting results. MATERIALS AND METHODS: We assessed dorsal
striatal (caudate and putamen) volumes bilaterally in 22 never-treated, non
substance-abusing patients with first-episode schizophrenia or schizophreniform
disorder and 23 healthy controls matched for age, sex and educational status.
Patients received either risperidone or flupenthixol long acting injection and
were compared by structural MRI with controls at weeks 0, 4 and 13. T1-weighted
data on a 3T MRI scanner were obtained and images were reconstructed using
FreeSurfer. Treatment outcome was assessed by changes in psychopathology,
insight, functionality, cognitive performance and motor symptoms. RESULTS:
Caudate, but not putamen volumes was significantly larger in patients bilaterally
at baseline (P=0.01). Linear mixed effects repeated measures found no significant
group * time interactions for any of the regions. Caudate volume was not
significantly associated with improvements in psychotic symptoms. Also, the
findings of a regression model were inconsistent insofar as larger caudate volume
was associated with less improvement in depression scores, greater improvement in
functionality and greater improvement in verbal learning but less improvement in
reasoning and problem solving (left caudate) and composite cognitive score (right
caudate). CONCLUSIONS: The increased caudate volumes prior to treatment are
contrary to previous reports in never-treated patients with first-episode
schizophrenia, and together with our failure to demonstrate volume changes
related to acute treatment, call into question previous proposals that enlarged
caudate volume is a consequence of antipsychotic treatment.
PMID- 26441007
TI - Conceptual disorganization weakens links in cognitive pathways: Disentangling
neurocognition, social cognition, and metacognition in schizophrenia.
AB - Disentangling links between neurocognition, social cognition, and metacognition
offers the potential to improve interventions for these cognitive processes.
Disorganized symptoms have shown promise for explaining the limiting relationship
that neurocognition holds with both social cognition and metacognition. In this
study, primary aims included: 1) testing whether conceptual disorganization, a
specific disorganized symptom, moderated relationships between cognitive
processes, and 2) examining the level of conceptual disorganization necessary for
links between cognitive processes to break down. To accomplish these aims,
comprehensive assessments of conceptual disorganization, neurocognition, social
cognition, and metacognition were administered to 67 people with schizophrenia
spectrum disorders. We found that conceptual disorganization significantly
moderated the relationship between neurocognition and metacognition, with links
between cognitive processes weakening when conceptual disorganization is present
even at minimal levels of severity. There was no evidence that conceptual
disorganization-or any other specific disorganized symptom-drove the limiting
relationship of neurocognition on social cognition. Based on our findings,
conceptual disorganization appears to be a critical piece of the puzzle when
disentangling the relationship between neurocognition and metacognition. Roles of
specific disorganized symptoms in the neurocognition - social cognition
relationship were less clear. Findings from this study suggest that disorganized
symptoms are an important treatment consideration when aiming to improve
cognitive impairments.
PMID- 26441008
TI - The effect of lifestyle interventions on the quality of life of gynaecological
cancer survivors: A systematic review and meta-analysis.
AB - OBJECTIVE: We aimed to evaluate the effectiveness of lifestyle interventions in
improving the quality of life (QoL) of endometrial and ovarian cancer survivors.
METHODS: The review was performed according to Preferred Reporting Items for
Systematic reviews and Meta-Analyses (PRISMA) guidelines, and the Cochrane
Handbook for Systematic Reviews of Interventions. We performed a search of
MEDLINE (1946-2015), EMBASE (1980-2015), CINAHL (1981-2015), PsycINFO (1806-2015)
and the Cochrane Trial Register to identify studies evaluating the effect of
lifestyle interventions on the QoL of endometrial and ovarian cancer survivors.
RESULTS: Eight studies fulfilled the inclusion criteria and comprised a total of
413 patients. Three studies were randomised controlled trials (RCTs), which
showed that lifestyle interventions may improve physical functioning and
significantly reduce fatigue in endometrial cancer survivors. In addition,
lifestyle interventions in endometrial cancer survivors resulted in significant
weight loss and improved physical activity levels, but did not show improvements
in global QoL in the meta-analysis (P=0.75, P=0.49). Non-randomised trials in
ovarian cancer survivors support the feasibility of lifestyle interventions and
suggest they may result in QoL improvements. CONCLUSIONS: Lifestyle interventions
have the potential to improve the QoL of endometrial cancer and ovarian cancer
survivors, and may significantly reduce fatigue. However, the current evidence is
limited and there is a need for future studies to further evaluate lifestyle
interventions and their effect on QoL outcomes.
PMID- 26441010
TI - Cancer Recurrence and Regional Anesthesia: The Theories, the Data, and the Future
in Outcomes.
AB - OBJECTIVE: More than one million people each year in the United States are
diagnosed with cancer. Surgery is considered curative, but the perioperative
phase represents a vulnerable period for residual disease to spread. Regional
anesthesia has been proposed to reduce the incidence of recurrence by attenuating
the sympathetic nervous system's response during surgery, reducing opioid
requirements thus diminishing their immunosuppressant effects, and providing
antitumor and anti-inflammatory effects directly through systemic local
anesthetic action. In this article, we present a description of the perioperative
period, a summary of the proposed hypotheses and available literature on the
effects of regional anesthesia on cancer recurrence, and put regional anesthesia
in context in regard to its potential role in reducing cancer recurrence during
the perioperative period. METHODS: A literature review was conducted through
PubMed by examining the following topics: effects of surgery on tumor
progression, roles of multiple perioperative variables (analgesics, hypothermia,
blood transfusion, beta-blockade) in cancer recurrence, and available in vitro,
animal, and human studies regarding the effects of regional anesthesia on cancer
recurrence. RESULTS: in vitro, animal and human retrospective studies suppport
the hypothesis that in certain types of cancer, regional anesthesia may be
associated with lower recurrence rates. A few well-planned human randomized
clinical trials are currently under way that may provide more solid evidence to
substantiate or refute the benefits of regional anesthesia in reducing cancer
recurrence. CONCLUSIONS: The benefits of regional anesthesia in reducing cancer
recurrence have a sound theoretical basis and, in certain cancers, are supported
by the existing body of literature. This article outlines the current state of
our knowledge on the relationship between cancer progression and regional
analgesia.
PMID- 26441011
TI - Exogenous brain-derived neurotrophic factor relieves pain symptoms of diabetic
rats by reducing excitability of dorsal root ganglion neurons.
AB - Diabetic peripheral neuropathy (DPN) is a common complication of diabetes lacking
of effective treatments. Enhanced excitability of dorsal root ganglion (DRG)
neuron plays a crucial role in the progression of diabetic neuropathic
hyperalgesia. Brain-derived neurotrophic factor (BDNF) is known as a
neuromodulator of nociception, but whether and how BDNF modulates the
excitability of DRG neurons in the development of DPN remain to be clarified.
This study investigated the role of exogenous BDNF and its high-affinity
tropomyosin receptor kinase B (TrkB) in rats with streptozotocin-induced diabetic
neuropathic pain. The results showed that continued intrathecal administration of
BDNF to diabetic rats dramatically alleviated mechanical and thermal
hyperalgesia, as well as inhibited hyperexcitability of DRG neurons. These
effects were blocked by pretreatment with TrkB Fc (a synthetic fusion protein
consisting of the extracellular ligand-binding domain of the TrkB receptor). The
expression of BDNF and TrkB was upregulated in the DRG of diabetic rats.
Intrathecal administration of BDNF did not affect this upregulation. These data
provide novel information that exogenous BDNF relieved pain symptoms of diabetic
rats by reducing hyperexcitability of DRG neurons and might be the potential
treatment of painful diabetic neuropathy.
PMID- 26441009
TI - Disparate Mutations Confer Therapeutic Gain of Hsp104 Function.
AB - Hsp104, a protein disaggregase from yeast, can be engineered and potentiated to
counter TDP-43, FUS, or alpha-synuclein misfolding and toxicity implicated in
neurodegenerative disease. Here, we reveal that extraordinarily disparate
mutations potentiate Hsp104. Remarkably, diverse single missense mutations at 20
different positions interspersed throughout the middle domain (MD) and small
domain of nucleotide-binding domain 1 (NBD1) confer a therapeutic gain of Hsp104
function. Moreover, potentiation emerges from deletion of MD helix 3 or 4 or via
synergistic missense mutations in the MD distal loop and helix 4. We define the
most critical aspect of Hsp104 potentiation as enhanced disaggregase activity in
the absence of Hsp70 and Hsp40. We suggest that potentiation likely stems from a
loss of a fragilely constrained autoinhibited state that enables precise
spatiotemporal regulation of disaggregase activity.
PMID- 26441012
TI - Pathogenicity and tissue tropism of currently circulating highly pathogenic avian
influenza A virus (H5N1; clade 2.3.2) in tufted ducks (Aythya fuligula).
AB - Reports describing the isolation of highly pathogenic avian influenza (HPAI)
virus (H5N1) clade 2.3.2 in feces from apparently healthy wild birds and the
seemingly lower pathogenicity of this clade compared to clade 2.2 in several
experimentally infected species, caused concern that the new clade might be
maintained in the wild bird population. To investigate whether the pathogenicity
of a clade 2.3.2 virus was lower than that of clades previously occurring in free
living wild birds in Europe, four tufted ducks were inoculated with influenza
A/duck/HongKong/1091/2011 (H5N1) clade 2.3.2 virus. The ducks were monitored and
sampled for virus excretion daily during 4 days, followed by pathologic,
immunohistochemical, and virological investigations. The virus produced severe
disease as evidenced by clinical signs, presence of marked lesions and abundant
viral antigen in several tissues, especially the central nervous system. The
study shows that HPAI-H5N1 virus clade 2.3.2 is highly pathogenic for tufted
ducks and thus, they are unlikely to maintain this clade in the free-living
population or serve as long-distance vectors.
PMID- 26441013
TI - Schmallenberg disease in sheep or goats: Past, present and future.
AB - Schmallenberg disease has emerged in North-Western Europe in 2011 and has since
spread widely, even across the European borders. It has the potency to infect
many, mainly ruminant, species, but seems to lack zoonotic potential. Horizontal
transmission occurs through various Culicoides biting midges and subsequent trans
placental transmission causes teratogenic effects. In some small ruminants,
clinical signs, including fever, decreased milk production and diarrhea occur
during the viraemic phase, but infection is mostly asymptomatic. However, fetal
Schmallenberg virus infection in naive ewes and goats can result in stillborn
offspring, showing a congenital arthrogryposis-hydranencephaly syndrome. The
economic impact of infection depends on the number of malformed lambs, but is
generally limited. There is debate on whether Schmallenberg virus has newly
emerged or is re-emerging, since it is likely one of the ancestors of Shamonda
virus, both Orthobunyaviruses belonging to the species Sathuperi virus within the
Simbu serogroup viruses. Depending on the vector-borne transmission and the
serologic status, future outbreaks of Schmallenberg disease induced congenital
disease are expected.
PMID- 26441014
TI - Regional volumes in brain stem and cerebellum are associated with postural
impairments in young brain-injured patients.
AB - Many patients with traumatic brain injury (TBI) suffer from postural control
impairments that can profoundly affect daily life. The cerebellum and brain stem
are crucial for the neural control of posture and have been shown to be
vulnerable to primary and secondary structural consequences of TBI. The aim of
this study was to investigate whether morphometric differences in the brain stem
and cerebellum can account for impairments in static and dynamic postural control
in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three
challenging postural control tasks on the EquiTest(r) system (Neurocom).
Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with
cerebellum-optimized voxel-based morphometry using the spatially unbiased
infratentorial toolbox. Volume loss in TBI patients was revealed in global
cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and
midbrain. In the TBI group and across both groups, lower postural control
performance was associated with reduced GM volume in the vermal/paravermal
regions of lobules I-IV, V and VI. Moreover, across all participants, worse
postural control performance was associated with lower WM volume in the pons,
medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This
is the first study in TBI patients to demonstrate an association between postural
impairments and reduced volume in specific infratentorial brain areas. Volumetric
measures of the brain stem and cerebellum may be valuable prognostic markers of
the chronic neural pathology, which complicates rehabilitation of postural
control in TBI.
PMID- 26441015
TI - Cellular Signaling in Metabolic Syndrome.
PMID- 26441016
TI - The possible interaction between periostin expressed by cancer stroma and tumor
associated macrophages in developing mycosis fungoides.
AB - Mycosis fungoides (MF) starts as an indolent disease, progresses from a patch
stage to confluent plaques and ultimately develops skin tumors. Tumor-associated
macrophages (TAMs) play roles in maintaining the tumor microenvironment in MF.
The purpose of this study was to elucidate the involvement of TAMs in the
lesional skin of different stages of MF. First, we immunohistologically examined
the percentage of CD163+ macrophages and CD206+ cells, as well as the levels of
periostin and IL-4 in cancer stroma. The percentage of CD206+ cells increased in
parallel with tumor progression, while there was no significant difference in the
percentage of CD163+ cells. Periostin was prominent in the stromal area at the
patch and plaque stages but decreased at the tumor stage. In contrast, IL-4 was
prominently stained at both plaque and tumor stages. To further elucidate the
molecular mechanisms of the effects of these stromal factors on TAMs, we examined
their effects on mRNA expression in monocyte-derived macrophages in vitro. Based
on microarray analysis and gene ontology, we examined a series of chemokines and
MMPs whose expression was strongly connected with periostin stimulation. The DNA
microarray results were verified in M2 macrophages using real-time PCR. We
further examined the mRNA expression of these chemokines and MMPs in the presence
of periostin and IL-4 to simulate the advanced stages of MF and validated their
protein expression by ELISA. Our present report suggests possible roles of
periostin on TAMs in establishing the tumor microenvironment in MF.
PMID- 26441018
TI - Tonsillolithiasis.
PMID- 26441017
TI - Breast pain and imaging.
AB - Breast pain is a common reason for consultation and a source of anxiety for
patients. Cyclical breast pain can be distinguished from non-cyclical pain and
breast pain with other symptoms. Many causes, usually benign are possible and the
clinical enquiry and physical examination are essential to establish predisposing
factors. Although imaging is not always needed for isolated breast pain, it is
still useful for the diagnosis of specific causes such as tension cysts, giant
adenofibromas or Mondor's thrombophlebitis. Ultrasound is the first line
investigation before mammography, MRI or biopsy, which may be indicated for
suspicious abnormalities. Some cancers may be associated with pain, which implies
that radiologists and physicians should always take breast pain seriously.
PMID- 26441019
TI - Acute pelvic pain in females in septic and aseptic contexts.
AB - Acute pelvic pain in women is a common reason for emergency department admission.
There is a broad range of possible aetiological diagnoses, with gynaecological
and gastrointestinal causes being the most frequently encountered. Gynaecological
causes include upper genital tract infection and three types of surgical
emergency, namely ectopic pregnancy, adnexal torsion, and haemorrhagic ovarian
cyst rupture. The main gastrointestinal cause is acute appendicitis, which is the
primary differential diagnosis for acute pelvic pain of gynaecological origin.
The process of diagnosis will be guided by the clinical examination, laboratory
study results, and ultrasonography findings, with suprapubic transvaginal pelvic
ultrasonography as the first-line examination in this young population, and
potentially cross-sectional imaging findings (computed tomography and MR imaging)
if diagnosis remains uncertain.
PMID- 26441020
TI - Chronic pelvic pain: An imaging approach.
AB - Chronic pelvic pain is defined as disabling pain of at least six months duration.
Chronic pelvic pain has often multiple causative factors. Careful analysis of
clinical history and detailed clinical examination must be carried out to guide
further imaging investigations. Endometriosis is a common cause of chronic pelvic
pain, although there is no correlation between the severity of lesions and pain
intensity. Pelvic ultrasonography should be the first line imaging examination to
search for causative conditions that include endometriosis, adenomyosis, pelvic
varices and chronic infection. Magnetic resonance imaging (MRI) is useful for
making the positive diagnosis and assessing the spread of endometriosis. MRI is
more accurate than ultrasonography for the diagnosis of tubo-ovarian abscess when
an adnexal mass is identified. Duplex and color Doppler ultrasonography as well
as MR angiography are the best imaging technique for the diagnosis of pelvic
congestion syndrome. In patients with pudendal neuralgia, cross-sectional imaging
help exclude nerve compression.
PMID- 26441021
TI - Pharmacokinetics and pharmacodynamics of gamithromycin in pulmonary epithelial
lining fluid in naturally occurring bovine respiratory disease in multisource
commingled feedlot cattle.
AB - The objectives of this study were to determine (i) whether an association exists
between individual pharmacokinetic parameters and treatment outcome when feeder
cattle were diagnosed with bovine respiratory disease (BRD) and treated with
gamithromycin (Zactran((r)) ) at the label dose and (ii) whether there was a
stronger association between treatment outcome and gamithromycin concentration in
plasma or in the pulmonary epithelial lining fluid (PELF) effect compartment. The
study design was a prospective, blinded, randomized clinical trial utilizing
three groups of 60 (362-592 lb) steers/bulls randomly allocated within origin to
sham injection or gamithromycin mass medication. Cattle were evaluated daily for
signs of BRD by a veterinarian blinded to treatment. Animals meeting the BRD case
definition were enrolled and allocated to a sample collection scheme consisting
of samples for bacterial isolation (bronchoalveolar lavage fluid and
nasopharyngeal swabs) and gamithromycin concentration determination (PELF and
plasma). Gamithromycin susceptibility of M. haemolytica (n = 287) and P.
multocida (n = 257) were determined using broth microdilution with frozen panels
containing gamithromycin at concentrations from 0.03 to 16 MUg/mL. A two
compartment plasma pharmacokinetic model with an additional compartment for
gamithromycin in PELF was developed using rich data sets from published and
unpublished studies. The sparse data from our study were then fit to this model
using nonlinear mixed effects modeling to estimate individual parameter values.
The resulting parameter estimates were used to simulate full time-concentration
profiles for each animal in this study. These profiles were analyzed using
noncompartmental methods so that PK/PD indices (AUC24 /MIC, AUCinfinity /MIC,
CMAX /MIC) could be calculated for plasma and PELF (also T>MIC) for each
individual. The calculated PK/PD indices were indicative that for both M.
haemolytica and P. multocida a higher drug exposure in terms of concentration,
and duration of exposure relative to the MIC of the target pathogen, was
favorable to a successful case outcome. A significant association was found
between treatment success and PELF AUC0-24 /MIC for P. multocida. The calves in
this study demonstrated an increased clearance and volume of distribution in
plasma as compared to the healthy calves in two previously published reports.
Ultimately, the findings from this study indicate that higher PK/PD indices were
predictive of positive treatment outcomes.
PMID- 26441022
TI - Synthesis of Azulen-1-yl Ketones via Oxidative Cleavage of C-C Multiple Bonds in
N-Sulfonyl Enamides and 1-Alkynes under Air and Natural Sunlight.
AB - A synthetic method to prepare azulen-1-yl ketones was developed via oxidative
cleavage of the C-C double bond in the reaction of easily obtainable N-sulfonyl
enamides with Cs2CO3 under air and natural sunlight and in the absence of a
photosensitizer. Oxidative cleavage of C-C triple bonds was also demonstrated for
the synthesis of azulen-1-yl ketones via a tandem Cu-catalyzed [3 + 2]
cycloaddition, Rh-catalyzed arylation, photooxygenation, and ring-opening
reaction in one pot under air and natural sunlight.
PMID- 26441023
TI - Are Dimensions of Parenting Differentially Linked to Substance Use Across
Caucasian and Asian American College Students?
AB - BACKGROUND: Parental warmth and autonomy granting are commonly thought of as
protective factors against substance use among Caucasians. However, limited
research has examined whether associations between parenting dimensions and
substance use outcomes are the same or different among Asian Americans. METHOD: A
final analytic sample of 839 college students was used to test whether race
(Caucasian vs. Asian American) moderated the relations between parenting
dimensions and substance use outcomes across Caucasians and Asian Americans. We
utilized the Parental Bonding Instrument (Parker, Tupling, & Brown, 1979) to
measure maternal and paternal warmth, encouragement of behavioral freedom, and
denial of psychological autonomy. RESULTS: Multivariate regression models
controlling for covariates including age, gender, and paternal education
indicated four significant parenting by race interactions on alcohol problems
and/or marijuana use. Specifically, maternal warmth was inversely associated with
both alcohol problems and marijuana use among Caucasians but not among Asian
Americans. Both maternal and paternal denial of psychological autonomy were
positively associated with alcohol problems among Caucasians but not among Asian
Americans. CONCLUSIONS: Consistent with emerging cross-cultural research, the
associations between parenting dimensions and substance use behaviors observed in
Caucasian populations may not be readily generalized to Asian Americans. These
findings highlight the importance of considering different parenting dimensions
in understanding substance use etiology among Asian Americans. Future research
should use longitudinal data to replicate these findings across development and
seek to identify other parenting dimensions that may be more relevant for Asian
American youth.
PMID- 26441024
TI - Source investigation of two outbreaks of skin and soft tissue infection by
Mycobacterium abscessus subsp. abscessus in Venezuela.
AB - Outbreaks of soft tissue or skin infection due to non-tuberculous mycobacteria
are reported frequently in scientific journals but in general the infection
source in these outbreaks remains unknown. In Venezuela, in two distinct
outbreaks, one after breast augmentation surgery and another after hydrolipoclasy
therapy, 16 patients contracted a soft tissue infection due to Mycobacterium
abscessus subsp. abscessus. Searching for the possible environmental infection
sources in these outbreaks, initially the tap water (in the hydrolipoclasy
therapy outbreak) and a surgical skin marker (in the breast implant surgery
outbreak), were identified as the infection sources. Molecular typing of the
strains with a variable number tandem repeat typing assay confirmed the tap water
as the infection source but the molecular typing technique excluded the skin
marker. We discuss the results and make a call for the implementation of
stringent hygiene and disinfection guidelines for cosmetic procedures in
Venezuela.
PMID- 26441025
TI - Tunable Mechanics in Electrospun Composites via Hierarchical Organization.
AB - Design strategies from nature provide vital clues for the development of
synthetic materials with tunable mechanical properties. Employing the concept of
hierarchy and controlled percolation, a new class of polymer nanocomposites
containing a montmorillonite (MMT)-reinforced electrospun poly(vinyl alcohol)
(PVA) filler embedded within a polymeric matrix of either poly(vinyl acetate)
(PVAc) or ethylene oxide-epichlorohydrin copolymer (EO-EPI) were developed to
achieve a tunable mechanical response upon exposure to specific stimuli.
Mechanical response and switching times upon hydration were shown to be dependent
on the weight-fraction of MMT in the PVA electrospun fibers and type of composite
matrix. PVA/MMT.PVAc composite films retained excellent two-way switchability for
all MMT fractions; however, the switching time upon hydration was decreased
dramatically as the MMT content was increased due to the highly hydrophilic
nature of MMT. Additionally, for the first time, significant two-way
switchability of PVA/MMT.EO-EPI composites was achieved for higher weight
fractions (12 wt %) of MMT. An extensive investigation into the effects of fiber
diameter, crystallinity, and MMT content revealed that inherent rigidity of MMT
platelets plays an important role in controlling the mechanical response of these
hierarchical electrospun composites.
PMID- 26441026
TI - Biocatalysis conversion of methanol to methane in an upflow anaerobic sludge
blanket (UASB) reactor: Long-term performance and inherent deficiencies.
AB - Long-term performance of methanol biocatalysis conversion in a lab-scale UASB
reactor was evaluated. Properties of granules were traced to examine the impact
of methanol on granulation. Methanolic wastewater could be stably treated during
initial 240d with the highest biogas production rate of 18.6 +/- 5.7 L/Ld at OLR
48 g-COD/Ld. However, the reactor subsequently showed severe granule
disintegration, inducing granule washout and process upsets. Some steps (e.g.
increasing influent Ca(2+) concentration, etc.) were taken to prevent rising
dispersion, but no clear improvement was observed. Further characterizations in
granules revealed that several biotic/abiotic factors all caused the dispersion:
(1) depletion of extracellular polymeric substances (EPS) and imbalance of
protein/polysaccharide ratio in EPS; (2) restricted formation of hard core and
weak Ca-EPS bridge effect due to insufficient calcium supply; and (3)
simplification of species with the methanol acclimation. More efforts are
required to solve the technical deficiencies observed in methanolic wastewater
treatment.
PMID- 26441027
TI - Production of biohydrogen from crude glycerol in an upflow column bioreactor.
AB - A continuous attached growth process for the production of biohydrogen from crude
glycerol was developed. The process consisted of an anaerobic up-flow column
bioreactor (UFCB), packed with cylindrical ceramic beads, which constituted the
support matrix for the attachment of bacterial cells. The effect of crude
glycerol concentration, pH and hydraulic retention time on glycerol conversion,
hydrogen yield and metabolite distribution was investigated. It was shown that
the most critical parameter for the efficient bioconversion was the pH of the
influent, whereas the hydrogen yield increased with an increase in feed glycerol
concentration and a decrease in the hydraulic retention time. The main soluble
metabolite detected was 1,3-propanediol in all cases, followed by butyric and
hexanoic acids. The latter is reported to be produced from glycerol for the first
time. Acidification of the waste reached 38.5%, and the maximum H2 productivity
was 107.3 +/- 0.7 L/kg waste glycerol at optimal conditions.
PMID- 26441028
TI - Simultaneous conversion of glucose and xylose to 3-hydroxypropionic acid in
engineered Escherichia coli by modulation of sugar transport and glycerol
synthesis.
AB - Escherichia coli expressing the Lactobacillus brevis dhaB1B2B3 and dhaR1R2
clusters and Pseudomonas aeruginosa aldhH was engineered to produce 3-HP from
glucose and xylose via the glycerol biosynthetic pathway. Glycerol, a key
precursor for 3-HP biosynthesis was produced by overexpression of the GPD1 and
GPP2 genes from Saccharomyces cerevisiae. For relief of carbon catabolite
repression, deletion of the chromosomal ptsG gene and overexpression of the
endogenous xylR gene rendered engineered E. coli JHS01300/pCPaGGRm to utilize
glucose and xylose simultaneously and to produce glycerol at 0.48 g/g yield and
0.35 g/L-h productivity. Finally, engineered E. coli JHS01300/pELDRR+pCPaGGRm
produced 29.4 g/L of 3-HP with 0.54 g/L-h productivity and 0.36 g/g yield in a
sugar-limited fed-batch fermentation. It was concluded that dual modulation of
sugar transport and glycerol biosynthesis is a promising strategy for efficient
conversion of glucose and xylose to 3-HP.
PMID- 26441029
TI - Nuclease stability of boron-modified nucleic acids: application to label-free
mismatch detection.
AB - 5'-End boronic acid-modified oligonucleotides were evaluated against various
nucleases at single and double stranded levels. The results show that these
modifications induce a high resistance to degradation by calf-spleen and snake
venom phosphodiesterases. More importantly, this eventually led to the
development of a new label-free enzyme-assisted fluorescence-based method for
single mismatch detection.
PMID- 26441030
TI - Competitive SWIFT cluster templates enhance detection of aging changes.
AB - Clustering-based algorithms for automated analysis of flow cytometry datasets
have achieved more efficient and objective analysis than manual processing.
Clustering organizes flow cytometry data into subpopulations with substantially
homogenous characteristics but does not directly address the important problem of
identifying the salient differences in subpopulations between subjects and
groups. Here, we address this problem by augmenting SWIFT--a mixture model based
clustering algorithm reported previously. First, we show that SWIFT clustering
using a "template" mixture model, in which all subpopulations are represented,
identifies small differences in cell numbers per subpopulation between samples.
Second, we demonstrate that resolution of inter-sample differences is increased
by "competition" wherein a joint model is formed by combining the mixture model
templates obtained from different groups. In the joint model, clusters from
individual groups compete for the assignment of cells, sharpening differences
between samples, particularly differences representing subpopulation shifts that
are masked under clustering with a single template model. The benefit of
competition was demonstrated first with a semisynthetic dataset obtained by
deliberately shifting a known subpopulation within an actual flow cytometry
sample. Single templates correctly identified changes in the number of cells in
the subpopulation, but only the competition method detected small changes in
median fluorescence. In further validation studies, competition identified a
larger number of significantly altered subpopulations between young and elderly
subjects. This enrichment was specific, because competition between templates
from consensus male and female samples did not improve the detection of age
related differences. Several changes between the young and elderly identified by
SWIFT template competition were consistent with known alterations in the elderly,
and additional altered subpopulations were also identified. Alternative
algorithms detected far fewer significantly altered clusters. Thus SWIFT template
competition is a powerful approach to sharpen comparisons between selected groups
in flow cytometry datasets.
PMID- 26441032
TI - When has enough evidence accumulated to change neonatal practice?
AB - Randomized clinical trials are the best method to assess the safety and efficacy
of therapeutic interventions. However, it is not always clear how much evidence
from randomized trials is required to change clinical practice. Throughout the
history of neonatal medicine, some therapies were subject to excessive and
unnecessary testing through replication of clinical trials. Other therapies were
adopted into clinical practice with insufficient evidence. In only a few cases
was the right amount of evidence accumulated to drive a change in practice. Here
we present a case history for each of these three scenarios. Arising from these,
we suggest principles to identify when enough evidence exists for a therapy to
become standard practice.
PMID- 26441031
TI - Alleviation of skin inflammation after Lin(-) cell transplantation correlates
with their differentiation into myeloid-derived suppressor cells.
AB - To understand the cellular mechanism underlying the therapeutic effects exerted
by hematopoietic stem cell transplantation in the repair of tissue damage, we
investigated the in vivo dynamics of bone marrow (BM) lineage-negative (Lin(-))
cells transplanted into mice with hyper sensitivity dermatitis. Longitudinal in
vivo imaging and flow cytometry analyses revealed that Lin(-) cells home directly
to inflamed skin within 6 h, where they undergo extensive expansion with the peak
on day 14 post-transplantation, and preferential differentiation into
CD11b(+)Ly6G(int)Ly6C(+) cells by day 7. Cells with phenotypic profiles of
neutrophils, macrophages, and DCs appeared in inflamed skin on day 14. Progenies
of transplanted Lin(-) cells showed similar kinetics of expansion and myeloid
differentiation in BM. However, differentiation into CD11b(+)Ly6G(int)Ly6C(+)
cells in the inflamed skin on day 7 was more skewed toward CD115(+) cells (>=60%)
with immune suppressive function and higher expression levels of iNOS, arginase,
and IL-10, compared with those in the BM. Transplantation of Lin(-) cells reduced
the levels of Cd3 transcript and CD4(+)/CD8(+) cells in inflamed skin. These
results demonstrate differentiation of transplanted Lin(-) cells into myeloid
derived suppressor cells in inflamed skin to be the basis of the alleviation of
skin inflammation after Lin(-) cell transplantation.
PMID- 26441033
TI - Molecular characterization of T-cell immunoglobulin mucin domain-3 and Galectin-9
genes of swamp- and riverine-type water buffaloes.
AB - Molecular characterization of T-cell immunoglobulin mucin domain-3 (TIM-3) and
Galectin-9 (GAL-9) genes of swamp- and riverine-type water buffaloes was
conducted to compare these genes with other species; determine the unique
characteristic specific in water buffalo; and provide baseline information for
the assessment of disease progression in buffalo species. TIM-3 and GAL-9 genes
were amplified, purified, sequenced and characterized. The sequence result of TIM
3 in both types of water buffaloes contained 843 nucleotides encoding to 280
amino acids while GAL-9 of swamp-type and riverine-type water buffaloes contained
1023 and 972 nucleotides encoding to 340 and 323 amino acids, respectively.
Meanwhile, the nucleotide and amino sequence of TIM-3 in water buffalo were 83
98% and 94-97% identical with other artiodactyl species, respectively. On the
other hand, GAL-9 nucleotide and amino acid sequence in water buffalo were 85-98%
and 76-96% identical with other artiodactyl species. The tyrosine-kinase
phosphorylation motif and potential glycosylation sites were conserved within the
tribe Bovinae. It is imperative to have further studies in the assessment of the
role of these genes in disease progression in water buffalo during chronic
infection. The study is the first report that describes the genetic
characteristic of TIM-3 and GAL-9 genes in water buffalo.
PMID- 26441034
TI - Pulsed Near-IR Photoresponse in a Bi-metal Contacted Graphene Photodetector.
AB - We use an ultra-fast near-infrared pulse coincidence technique to study the time,
temperature, and power dependence of the photoresponse of a bi-metal contacted
graphene photodetector. We observe two components of the photovoltage signal. One
component is gate-voltage dependent, linear in power at room temperature and sub
linear at low temperature-consistent with the hot-electron photothermoelectric
effect due to absorption in the graphene. The power dependence is consistent with
supercollision-dominated cooling in graphene. The other component is gate-voltage
independent and linear in temperature and power, which we interpret as due to
thermoelectricity of the metal electrodes due to differential light absorption.
PMID- 26441035
TI - Stromal cell-derived factor 1alpha (SDF-1alpha): A marker of disease burden in
patients with atrial fibrillation.
AB - OBJECTIVES: Stromal cell-derived factor 1a (SDF-1alpha), is a chemokine and is
able to home hematopoietic progenitor cells to injured areas of heart tissue for
structural repair. Previous studies have found increased levels of SDF-1alpha in
several cardiac diseases, but only few studies have investigated SDF-1alpha in
patients with atrial fibrillation (AF). We aimed to test SDF-1alpha in a large
cohort of patients with AF and its role as a prognostic marker. DESIGN: Between
January 1st 2008 to December 1st 2012, 290 patients with ECG documented AF were
enrolled from the in- and outpatient clinics at the Department of Cardiology,
Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark. Plasma levels of
SDF-1alpha were measured using ELISA technique. Clinical data were registered and
patient follow-up was conducted. RESULTS: Patients with permanent AF had
significantly higher SDF-1alpha levels (2199.5 pg/ml) than the patients with
paroxysmal AF (1982.0 pg/ml) and persistent AF (1906.0 pg/ml), p < 0.0005. Higher
SDF-1alpha level was associated with longer time spent in the hospital per
readmission, p < 0.05. CONCLUSION: In AF patients, a higher SDF-1alpha level was
found in patients with a more progressive state of arrhythmia and was associated
with longer hospitalizations. These findings suggest that SDF-1alpha could prove
valuable in risk stratification and evaluating the disease burden in AF patients.
PMID- 26441036
TI - Letter to the Editor: Examination of Potential Sex Influences in . Auditory
Function in Normal-Hearing, Noise-Exposed Human Ears, Ear Hear, 36, 172-184.
PMID- 26441037
TI - The use of circulating biomarkers in early clinical trials in patients with
cancer.
AB - The development of targeted therapies has changed the approach to early
oncological clinical trial design. Identification of patient populations most
likely to derive benefit and the biologically effective dose are now as important
as determination of the maximum tolerated dose. Completion of the
'pharmacological audit trail' highlights drugs most likely to progress through to
license, so resources can be allocated appropriately. Key to the success of this
changing model is the validation/qualification of circulating biomarkers. These
might provide a readily accessible and dynamic picture of drug effect, tumor
response and toxicity with minimum risk to patients. This review article examines
circulating biomarkers currently used in early oncological clinical trials. It
considers the evidence for their employment, limitations and challenges for
future development.
PMID- 26441038
TI - Giant cell tumour 2nd metatarsal-Result with en-bloc excision and autologous
fibular grafting.
AB - Giant cell tumour (GCT) of the small bones is relatively uncommon tumour. It
occurs most commonly in the distal portions of femur and radius and proximal end
of tibia. GCT of small bones presents at advanced stages with major bony
destruction. These tumours represent more aggressive course; associated with
increased local recurrence rates (40%) and metastasis. Various treatment
modalities like en-bloc resection, cryosurgery, intralesional curettage with
burring/phenolization or bone cement are available. In our case en-bloc resection
with reconstruction using nonvascular autogenous fibular strut graft was used in
patient of 2nd metatarsal GCT and a favourable functional outcome was observed.
PMID- 26441039
TI - Vitamin D insufficiency and deficiency in patients with fractures of the fifth
metatarsal.
AB - INTRODUCTION: The fifth metatarsal is a common site for both acute and stress
fractures in the foot. They are usually isolated low-energy or stress fractures.
Vitamin D deficiency has been associated with fragility fractures in many parts
of the body. We believe that low Vitamin D could be a significant aetiological
factor in fractures of the fifth metatarsal. METHODOLOGY: A prospective study of
patients with fractures of the fifth metatarsal was conducted. Patients
presenting to fracture clinic with these fractures had their vitamin D and
calcium levels measured. We also conducted a literature review of studies of
vitamin D levels in the Northern Hemisphere between 1990 and 2014. RESULTS: Forty
patients with fifth metatarsal fractures were studied (22 metatarsal base
fractures, 6 shaft fractures, and 2 stress fractures). The average patient age
was 49 (range 22-83). 12 patients (30%) had a Vitamin D level consistent with
deficiency, and a further 14 (35%) had a level consistent with insufficiency.
Average Vitamin D levels in winter fractures were significantly lower
(52.23nmol/L) than for those sustained in summer (76.73nmol/L). CONCLUSIONS:
Hypovitaminosis D was common in patients with fifth metatarsal fractures. Vitamin
D supplementation has been shown in animal studies to improve fracture healing
rates, and in humans to decrease the risk of fragility fracture. It should be
part of regular practice to check Vitamin D levels in these patients, and
supplement where necessary.
PMID- 26441040
TI - Occupational safety and health in the service of people.
PMID- 26441042
TI - RETRACTED: Targeting Mycobacterial Enzymes with Natural Products.
AB - Tuberculosis (TB) is a recurring threat to contemporary civilization. It affects
not only those within developing countries, but has also appeared again in places
where it was once considered eradicated. TB co-infection in patients infected by
HIV is, at the time of writing, the most common cause of death. In the field of
searching for new antimycobacterial drug leads, compounds of natural origin still
remain a promising source. The review is intended to gather information about
natural products (metabolites of plants, fungi, bacteria, and marine sponges)
that show activity against mycobacterial enzymes. Here, natural metabolites are
presented as being inhibitors/activators of the mycobacterial enzymes involved in
mycobacterial growth in vitro (ClpC1, ClpP, MurE ligase, mycothiol S-conjugate
amidase, beta-ketoacyl-ACP synthase, InhA) and in vivo, as regards the host cell
(PtpB). Each enzyme is briefly described so as to generate an understanding of
its role in mycobacterial growth and engender a perception of the mechanism of
action of the studied natural compounds. Furthermore, after the introduction of
the enzyme, its inhibitors are listed and exactly characterized.
PMID- 26441041
TI - Trends, predictors, and impact of systemic chemotherapy in small cell lung cancer
patients between 1985 and 2005.
AB - BACKGROUND: The last 3 decades have witnessed limited therapeutic advances in
small cell lung cancer (SCLC) management. This study evaluated real-world trends
in the use of systemic therapies and the impact on patient outcomes in the United
States. METHODS: The Surveillance, Epidemiology, and End Results-Medicare
database was used to find patients diagnosed with SCLC between 1985 and 2005. The
1985-1990 period served as the baseline for a temporal analysis conducted at 5
year intervals (1985-1990, 1991-1995, 1996-2000, and 2001-2005). Cox proportional
models were used to estimate the effect of chemotherapy on survival. Results were
validated with a propensity-matched analysis. RESULTS: There were 47,351 eligible
patients: 52% were male; the median age was 71 years; and 87% were white, 7% were
black, and 1.4% were Asian. The proportion of patients treated with chemotherapy
was low but increased over time (38%, 55%, 50%, and 53%; P < .001). Race,
diagnosis period, age, stage, and location of residence significantly predicted
chemotherapy use. Females (51%), Asians (53%), and rural residents (60%) were
more likely to receive chemotherapy. The median overall survival with and without
chemotherapy was 9.6 and 3.6 months, respectively. Linear trend analyses showed a
modest reduction in the impact of chemotherapy on survival for patients treated
with chemotherapy versus untreated patients (hazard ratios [HRs], 0.59, 0.61,
0.64, and 0.62; P < .001) but an overall trend of improved survival for treated
(HRs, 1.0, 1.03, 1.00, and 0.96; P = .005) and untreated patients (HRs, 1.0,
0.99, 0.94, and 0.92; P < .001). There was no survival difference between
patients treated with carboplatin and patients treated with cisplatin (HR, 0.99;
confidence interval [CI], 0.81-1.19; P = .875). Additional therapy beyond
platinum-based chemotherapy was associated with a survival benefit (HR, 0.78; CI,
0.75-0.81; P < .001). CONCLUSIONS: Chemotherapy use was associated with a
survival benefit in Medicare patients with SCLC treated in a real-world setting.
PMID- 26441043
TI - In-Depth High-Throughput Screening of Protein Engineering Libraries by Split-GFP
Direct Crude Cell Extract Data Normalization.
AB - Here, we report a widely and generally applicable strategy to obtain reliable
information in high-throughput protein screenings of enzyme mutant libraries. The
method is based on the usage of the split-GFP technology for the normalization of
the expression level of each individual protein variant combined with activity
measurements, thus resolving the important problems associated with the different
solubility of each mutant and allowing the detection of previously invisible
variants. The small size of the employed protein tag (16 amino acids) required
for the reconstitution of the GFP fluorescence reduces possible interferences
such as enzyme activity variations or solubility disturbances to a minimum.
Specific enzyme activity measurements without purification, in situ soluble
protein expression monitoring, and data normalization are the powerful outputs of
this methodology, thus enabling the accurate identification of improved protein
variants during high-throughput screening by substantially reducing the
occurrence of false negatives and false positives.
PMID- 26441044
TI - The validity of the Substance Use Risk Profile Scale (SURPS) among Australian
adolescents.
AB - AIMS: This study investigated the validity of a brief personality screening
measure for substance use in adolescents, the Substance Use Risk Profile Scale
(SURPS), among Australian adolescents. DESIGN AND PARTICIPANTS: A total of 527
adolescents (mean age: 13.38years, SD=0.43) from seven Australian schools were
assessed at two time points 24months apart. The concurrent and predictive
validity of the SURPS was determined using a series of linear and logistic
regressions, and was compared to the results in a United Kingdom (UK) sample.
SURPS subscale scores for the Australian population were also reported and
compared to those in the UK. FINDINGS: Overall, the SURPS subscale scores for
Australian adolescents were similar to those for adolescents from the UK. Tests
of concurrent and predictive validity in the Australian sample demonstrated that
the all four personality profiles - Hopelessness (H), Anxiety Sensitivity (AS),
Impulsivity (IMP), and Sensation Seeking (SS) - were related to measures of
substance use and other behavioural and emotional characteristics. In addition,
all the predicted specific prospective relationships between the personality
profiles and particular substance use and other behavioural problems were
confirmed except that H was not associated with illicit drug use. Overall, the
results were similar between the Australian and UK samples. CONCLUSIONS: The
SURPS is a valid and useful measure for identifying Australian adolescents at
high-risk for substance use and other emotional and behavioural problems.
Implications for prevention are discussed.
PMID- 26441045
TI - Motivation to quit as a predictor of smoking cessation and abstinence maintenance
among treated Spanish smokers.
AB - INTRODUCTION: Although quitting motivation predicts smoking cessation, there have
been inconsistent findings regarding motivation predicting long-term maintenance
of abstinence. Moreover, most such research has been conducted in North America
and the United Kingdom. The aim of this study was to examine motivation to quit
as a predictor of smoking cessation and of abstinence maintenance in a Spanish
sample. METHOD: The sample comprised 286 Spanish smokers undergoing psychological
treatment for smoking cessation. Motivation to quit was assessed pre-treatment
and post-treatment with the Readiness to Quit Ladder. Abstinence post-treatment
and at 6month follow-up was biochemically verified. RESULTS: Participants with
higher levels of pre-treatment and post-treatment motivation were more likely to
be abstinent at the end of the treatment (OR=1.36) and at 6month follow-up
(OR=4.88). Among abstainers at the end of the treatment (61.9%), higher levels of
motivation to quit post-treatment predicted maintaining abstinence at 6months
(OR=2.83). Furthermore, participants who failed to quit smoking reported higher
levels of motivation to quit post-treatment than they had pretreatment (p<.001).
CONCLUSIONS: Motivation to quit smoking predicted short and long-term cessation,
and also predicted long-term maintenance of abstinence. These results have
implications for understanding motivational processes of smoking cessation in
general, while extending research to Spanish smokers. They may also help in the
design of cessation and relapse-prevention interventions. Specifically, the
results suggest that motivational enhancement is important throughout the
cessation and maintenance periods.
PMID- 26441046
TI - Surprising trunk rotational capabilities in chimpanzees and implications for
bipedal walking proficiency in early hominins.
AB - Human walking entails coordinated out-of-phase axial rotations of the thorax and
pelvis. A long-held assumption is that this ability relies on adaptations for
trunk flexibility present in humans, but not in chimpanzees, other great apes, or
australopithecines. Here we use three-dimensional kinematic analyses to show
that, contrary to current thinking, chimpanzees walking bipedally rotate their
lumbar and thoracic regions in a manner similar to humans. This occurs despite
differences in the magnitude of trunk motion, and despite morphological
differences in truncal 'rigidity' between species. These results suggest that,
like humans and chimpanzees, early hominins walked with upper body rotations that
countered pelvic rotation. We demonstrate that even if early hominins walked with
pelvic rotations 50% larger than humans, they may have accrued the energetic and
mechanical benefits of out-of-phase thoracic rotations. This would have allowed
early hominins to reduce work and locomotor cost, improving walking efficiency
early in hominin evolution.
PMID- 26441047
TI - Current applications of in utero intervention for lower urinary tract
obstruction.
AB - PURPOSE: Since the early 1980s with the inception of fetal intervention for
obstructive uropathy, there have been creative attempts to improve both perinatal
and long-term outcomes. Despite advances in technology and an improved
understanding of lower urinary tract obstruction (LUTO) in the fetus, the results
for these therapeutic interventions remain guarded and the long-term renal
morbidity among survivors remains problematic. RECENT FINDINGS: Fetal LUTO
represents a range of disorders but the most common of these is posterior
urethral valves (PUVs). Selection criteria for candidates of possible
intervention have improved with our understanding of fetal renal physiology.
Serial urinalysis has marginally improved our ability to predict those that may
ultimately respond to treatment [1,2], but the potential in the development of
biomarkers for renal development or maldevelopment holds greater promise [3].
Advancements in fetal surgery may result in less fetal and maternal morbidity,
but limited long-term improvement in outcomes highlights the controversial nature
of the various interventions [4-10]. We must counsel families that fetal surgery
offers hope but we cannot allow them to hold unrealistic expectations for cure.
SUMMARY: In appropriately selected fetuses, intervention may improve perinatal
survival but not without risk to mother and fetus. Long-term renal outcomes
remain problematic amongst survivors. In the case of PUV, postnatal primary valve
ablation remains the cornerstone of treatment for nephron preservation; however,
our ability to mimic these results in the prenatal population remains poor [11].
Disease severity has likely predetermined those that will survive through the
perinatal period with or without intervention. Nonetheless, our drive to assess
and manage fetal obstructive uropathy perseveres so that we may ultimately
relieve obstruction and preserve renal and lung function. We must maintain
optimism that continued advances will ultimately improve outcomes, but also be
realistic with our current expectations. This paper reviews the status of current
in utero interventions and outcomes.
PMID- 26441048
TI - Anatomy of the cutaneous surface of the male genitalia, with elaboration upon the
inner preputial coronal-shaft junction.
AB - INTRODUCTION: Descriptions of the penile prepuce in anatomical and clinical texts
either omit details or contain a small, yet potentially serious, error with
regard to the manner of its attachment to the penis. OBJECTIVE: This study sought
to cast light on a ubiquitous but poorly understood and under-appreciated
structure, while correcting a long-standing mistake in the medical literature.
STUDY DESIGN: The foreskins of five male stillborn babies were dissected and
carefully examined. Tissue from the apposing surfaces of the various regions of
the inner and outer prepuce surfaces and the transition zone itself were
collected, embedded in paraffin, sectioned, stained, examined and photographed
under microscopy. RESULTS: Contradicting the prevailing descriptions in the
literature that the inner prepuce is a single, uniform sheath, this study's
observations and histological findings demonstrated that it actually splits into
separate laminae that connect distally to the shaft at the base of the corona and
proximally with the shaft fascia, respectively (Figure). DISCUSSION: The penile
prepuce is a discrete and deceptively complex part of the male anatomy, yet key
details of its interposing surfaces are inaccurately described or entirely
omitted in the literature. Understanding the normal anatomy of the prepuce is
critically relevant, particularly for urologists and others involved in the
performance of circumcision. For example, avoiding potentially catastrophic
avulsion of the inner preputial remnant beyond the coronal sulcus during
circumcision and accurate assessment of tissue positioning prior to penile
reconstruction in cases of hypospadias. CONCLUSION: The findings of this study
correct a misunderstanding in the anatomy of the prepuce.
PMID- 26441049
TI - Response to K.M. Szymanski re 'Further analysis of the glans-urethral meatus
shaft (GMS) hypospadias score: Correlation with postoperative complications'.
PMID- 26441050
TI - Cytokine modulation (IL-6, IL-8, IL-10) by human breast milk lipids on intestinal
epithelial cells (Caco-2).
AB - Human breast milk is the best form of nourishment for infants during the first
year of life. It is composed by a complex mixture of carbohydrates, proteins and
fats. Breast milk provides nutrients and bioactive factors that themselves
modulate maturation and development of the gastrointestinal tract. Many studies
have shown that it provides protection against gastrointestinal tract
inflammation. In this sense, this study aimed to evaluate the effect of human
breast milk lipids on epithelial intestinal cells (Caco-2) cytokine regulation
and the fatty acid transporter protein (FATP) involved in this process. Caco-2
cells were cultivated and stimulated with different concentration of human milk
lipids from healthy human mothers (18-30-year-olds) or single commercial lipids
for 48 h. We measured the concentrations and mRNA levels of IL-6, IL-8 and IL-10
cytokines by immunoassay (ELISA) and quantitative-PCR (qRT-PCR) technique,
respectively. We observed a two to three times decrease in pro-inflammatory
cytokine levels (p < 0.01) as well as an increase in anti-inflammatory IL-10
levels in cells stimulated with increasing concentrations of breast milk lipids.
These results suggest that human breast milk lipids could have an important role
on the cytokine modulation in the newborn bowel.
PMID- 26441051
TI - Genetics of endometriosis.
AB - Endometriosis is a heritable complex disorder that is influenced by multiple
genetic and environmental factors. Identification of these genetic factors will
aid a better understanding of the underlying biology of the disease. In this
article, we describe different methods of studying genetic variation of
endometriosis, summarize results from genetic studies performed to date and
provide recommendations for future studies to uncover additional factors
contributing to the heritable component of endometriosis.
PMID- 26441052
TI - Predicting complex mineral structures using genetic algorithms.
AB - We show that symmetry-adapted genetic algorithms are capable of finding the
ground state of a range of complex crystalline phases including layered- and
incommensurate super-structures. This opens the way for the atomistic prediction
of complex crystal structures of functional materials and mineral phases.
PMID- 26441053
TI - Arabidopsis NAC016 promotes chlorophyll breakdown by directly upregulating
STAYGREEN1 transcription.
AB - KEY MESSAGE: The Arabidopsis transcriptional factor NAC016 directly activates
chlorophyll degradation during leaf senescence by binding to the promoter of SGR1
and upregulating its transcription. During leaf senescence or abiotic stress in
Arabidopsis thaliana, STAYGREEN1 (SGR1) promotes chlorophyll (Chl) degradation,
acting with Chl catabolic enzymes, but the mechanism regulating SGR1
transcription remains largely unknown. Here, we show that the Arabidopsis
senescence-associated NAC transcription factor NAC016 directly activates SGR1
transcription. Under senescence-promoting conditions, the expression of SGR1 was
downregulated in nac016-1 mutants and upregulated in NAC016-overexpressing
(NAC016-OX) plants. By yeast one-hybrid and chromatin immunoprecipitation assays,
we found that NAC016 directly binds to the SGR1 promoter, which contains the
NAC016-specific binding motif (termed the NAC016BM). Furthermore, nac016-1 SGR1
OX plants showed an early leaf yellowing phenotype, similar to SGR1-OX plants,
confirming that NAC016 directly activates SGR1 expression in the leaf senescence
regulatory cascade. Although we found that NAC016 activates SGR1 expression in
senescing leaves, this transcriptional regulation is considerably weaker in
maturing seeds; the seeds of sgr1-1 mutants (also known as nonyellowing1-1, nye1
1) stayed green, while the seeds of nac016-1 mutants turned from green to yellow
normally. We also found that the abscisic acid (ABA) signaling-related
transcription factor genes ABI5 and EEL and the ABA biosynthesis gene AAO3, which
activate SGR1 expression directly or indirectly, were significantly downregulated
in nac016-1 mutants and upregulated in NAC016-OX plants. However, the NAC016BM
does not exist in their promoter regions, indicating that NAC016 may indirectly
activate these ABA signaling and biosynthesis genes, probably by directly
activating transcriptional cascades regulated by the NAC transcription factor
NAP. The NAC016-mediated regulatory cascades of SGR1 and other Chl degradation
related genes are discussed.
PMID- 26441054
TI - Fine mapping of a palea defective 1 (pd1), a locus associated with palea and
stamen development in rice.
AB - KEY MESSAGE : pd1, a genetic factor in a 69 kb region between RM11239 and RM11245
on rice chromosome 1, controls stamen number and palea development. Spikelets are
important organs that store photosynthetic products in rice. Spikelet development
directly affects grain yield and rice quality. Here, we report a palea defective
(pd1) mutant identified from selfing progenies of indica cv. 93-11 after (60)Co
gamma ray treatment. pd1 mutant flowers only had four stamens (wild-type has
six), but pollen fertility was not affected. Compared with 93-11 palea, pd1
mutant palea showed smaller and flatter leaf, which caused the lemma to bend
excessively inward. pd1 mutants had only 46% seed setting rate and 21.6 g 1000
grain weight, which led to two-thirds loss of grain yield. Scanning electron
microscope analysis revealed that pd1 mutants had reduced epidermal cell size and
reduced numbers of fibrous sclerenchyma cells in both palea and lemma. To analyze
the genetic factors involved, we crossed pd1 mutants with three japonica
cultivars and generated F1 and F2 populations. The F1 phenotype and F2
segregation ratio indicated that a recessive gene controlled the mutant traits.
Using the F2 population, we found that pd1 mapped between the simple sequence
repeat markers RM11236 and RM11280 on rice chromosome 1. From a segregating
population of 2836 plants, 77 recombinants were screened by RM11236 and RM11280.
High-resolution linkage analysis narrowed the pd1 locus to a 69 kb region between
RM11239 and RM11245 that contained 10 open reading frames (ORFs). Sequence
alignment and quantitative real-time PCR expression analysis of these ORFs
between 93-11 and pd1 mutant plants found no unequivocal evidence to identify the
pd1 gene.
PMID- 26441055
TI - The role of photorespiration during H2 photoproduction in Chlorella
protothecoides under nitrogen limitation.
AB - KEY MESSAGE: Photorespiration in Chlorella protothecoides plays an important role
in photoprotection of photosystem (PS) II in the late phase of H(2)
photoproduction, allowing PSII to supply more electrons to hydrogenase.
PMID- 26441056
TI - Artemisinin production by plant hairy root cultures in gas- and liquid-phase
bioreactors.
AB - KEY MESSAGE: Alternative biotechnological protocol for large-scale artemisinin
production was established. It featured enhanced growth and artemisinin
production by cultivation of hairy roots in nutrient mist bioreactor (NMB)
coupled with novel cultivation strategies. Artemisinin is used for the treatment
of cerebral malaria. Presently, its main source is from seasonal plant Artemisia
annua. This study featured investigation of growth and artemisinin production by
A. annua hairy roots (induced by Agrobacterium rhizogenes-mediated genetic
transformation of explants) in three bioreactor configurations-bubble column
reactor, NMB and modified NMB particularly to establish their suitability for
commercial production. It was observed that cultivation of hairy roots in a non
stirred bubble column reactor exhibited a biomass accumulation of 5.68 g/l only
while batch cultivation in a custom-made NMB exhibited a higher biomass
concentration of 8.52 g/l but relatively lower artemisinin accumulation of 0.22
mg/g was observed in this reactor. A mixture of submerged liquid-phase growth
(for 5 days) followed by gas-phase cultivation in nutrient mist reactor operation
strategy (for next 15 days) was adopted for hairy root cultivation in this
investigation. Reasonably, high (23.02 g/l) final dry weight along with the
artemisinin accumulation (1.12 mg/g, equivalent to 25.78 mg/l artemisinin) was
obtained in this bioreactor, which is the highest reported artemisinin yield in
the gas-phase NMB cultivation.
PMID- 26441057
TI - Investigation of the ASR family in foxtail millet and the role of ASR1 in
drought/oxidative stress tolerance.
AB - KEY MESSAGE: Six foxtail millet ASR genes were regulated by various stress
related signals. Overexpression of ASR1 increased drought and oxidative tolerance
by controlling ROS homeostasis and regulating oxidation-related genes in tobacco
plants. Abscisic acid stress ripening (ASR) proteins with ABA/WDS domains
constituted a class of plant-specific transcription factors, playing important
roles in plant development, growth and abiotic stress responses. However, only a
few ASRs genes have been characterized in crop plants and none was reported so
far in foxtail millet (Setaria italic), an important drought-tolerant crop and
model bioenergy grain crop. In the present study, we identified six foxtail
millet ASR genes. Gene structure, protein alignments and phylogenetic
relationships were analyzed. Transcript expression patterns of ASR genes revealed
that ASRs might play important roles in stress-related signaling and abiotic
stress responses in diverse tissues in foxtail millet. Subcellular localization
assays showed that SiASR1 localized in the nucleus. Overexpression of SiASR1 in
tobacco remarkably increased tolerance to drought and oxidative stresses, as
determined through developmental and physiological analyses of germination rate,
root growth, survival rate, relative water content, ion leakage, chlorophyll
content and antioxidant enzyme activities. Furthermore, expression of SiASR1
modulated the transcript levels of oxidation-related genes, including NtSOD,
NtAPX, NtCAT, NtRbohA and NtRbohB, under drought and oxidative stress conditions.
These results provide a foundation for evolutionary and functional
characterization of the ASR gene family in foxtail millet.
PMID- 26441058
TI - Engineering low phorbol ester Jatropha curcas seed by intercepting casbene
biosynthesis.
AB - KEY MESSAGE: Casbene is a precursor to phorbol esters and down-regulating casbene
synthase effectively reduces phorbol ester biosynthesis. Seed-specific reduction
of phorbol ester (PE) helps develop Jatropha seed cake for animal nutrition.
Phorbol esters (PEs) are diterpenoids present in some Euphorbiaceae family
members like Jatropha curcas L. (Jatropha), a tropical shrub yielding high
quality oil suitable as feedstock for biodiesel and bio jet fuel. Jatropha seed
contains up to 40 % of oil and can produce oil together with cake containing high
quality proteins. However, skin-irritating and cancer-promoting PEs make Jatropha
cake meal unsuitable for animal nutrition and also raise some safety and
environmental concerns on its planting and processing. Two casbene synthase gene
(JcCASA163 and JcCASD168) homologues were cloned from Jatropha genome and both
genes were highly expressed during seed development. In vitro functional analysis
proved casbene synthase activity of JcCASA163 in converting geranylgeranyl
diphosphate into casbene which has been speculated to be the precursor to PEs. A
seed-specific promoter driving inverted repeats for RNAi interference targeting
at either JcCASA163 or both genes could effectively down-regulate casbene
synthase gene expression with concurrent marked reduction of PE level (by as much
as 85 %) in seeds with no pleiotropic effects observed. Such engineered low PE in
seed was heritable and co-segregated with the transgene. Our work implicated
casbene synthase in Jatropha PE biosynthesis and provided evidence for casbene
being the precursor for PEs. The success in reducing seed PE content through down
regulation of casbene synthase demonstrates the feasibility of intercepting PE
biosynthesis in Jatropha seed to help address safety concerns on Jatropha
plantation and seed processing and facilitate use of its seed protein for animal
nutrition.
PMID- 26441059
TI - Interferon-beta Modulates the Innate Immune Response against Glioblastoma
Initiating Cells.
AB - Immunotherapy targeting glioblastoma initiating cells (GIC) is considered a
promising strategy. However, GIC are prone to evade immune response and there is
a need for potent adjuvants. IFN-beta might enhance the immune response and here
we define its net effect on the innate immunogenicity of GIC. The transcriptomes
of GIC treated with IFN-beta and controls were assessed by microarray-based
expression profiling for altered expression of immune regulatory genes. Several
genes involved in adaptive and innate immune responses were regulated by IFN
beta. We validated these results using reverse transcription (RT)-PCR and flow
cytometry for corresponding protein levels. The up-regulation of the NK cell
inhibitory molecules HLA-E and MHC class I was balanced by immune stimulating
effects including the up-regulation of nectin-2. In 3 out of 5 GIC lines tested
we found a net immune stimulating effect of IFN-beta in cytotoxicity assays using
NKL cells as effectors. IFN-beta therefore warrants further investigation as an
adjuvant for immunotherapy targeting GIC.
PMID- 26441060
TI - Experimental evidence for the therapeutic potential of tempol in the treatment of
acute liver injury.
AB - Oxidative stress is one of the mechanisms involved in the acute carbon
tetrachloride (CCl4)-induced hepatotoxicity. Since 4-hydroxy-2,2,6,6
tetramethylpiperidin-1-oxyl, known as tempol, has powerful antioxidant
properties, we investigated its potential hepatoprotective effects and the
underlying mechanisms that may add further benefits for its clinical usefulness
using an acute model of CCl4-induced hepatotoxicity. One hour after CCl4
induction of acute hepatotoxicity, mice were treated with a daily dose of 20
mg/kg/day tempol for 3 days. It was found that treatment of animals with tempol
significantly negated the pathological changes in liver function parameters as
well as histology induced by CCl4. In addition, tempol significantly ameliorated
CCl4-induced lipid peroxidation and GSH depletion, and improved catalase
activity. Furthermore, tempol alleviated the inflammation induced by CCl4 as
indicated by reducing the liver expression level of nuclear factor-kappa B (NF
kappaB) and tumor necrosis factor-alpha (TNF-alpha). Finally, tempol
significantly reduced expression level of the B-cell lymphoma-2 protein (Bcl-2)
and active caspase-3 which are known markers of apoptosis. In conclusion, the
present study provides important evidences for the promising hepatoprotective
effects of tempol that can be explained by amelioration of oxidative stress
mainly through replenishment of GSH, restoration of antioxidant enzyme
activities, and reduction of lipid peroxides alongside its anti-inflammatory
properties.
PMID- 26441061
TI - Dynamic analysis of phospholipid metabolism of mouse macrophages treated with
common non-steroidal anti-inflammatory drugs.
AB - Through studying the changes of the total phospholipid components in mouse
macrophages under the inflammatory status and the drug intervention status, we
found the targets of non-steroidal anti-inflammatory drugs on phospholipids, thus
providing the basis for the targets of in vitro anti-inflammatory effects of non
steroidal anti-inflammatory drugs. After RAW264.7 cells were pretreated with
common non-steroidal anti-inflammatory drugs (aspirin and ibuprofen) and,
respectively, stimulated with KLA for various periods (0.5, 4, 12, 16, and 24 h),
the phospholipids were extracted. The dynamic changes of phospholipids in cells
under various stimulations were analyzed with UPLC-Q-TOF-MS technique. Through
the statistical analysis of Simca-P, we explored the potential targets of non
steroidal anti-inflammatory drugs on phospholipids. Through the dynamic analysis
of phospholipids, we found two biomarkers (PC(17:1/18:1), PA(18:0/18:4)) which
might be in vitro intervention inflammatory response targets of non-steroidal
anti-inflammatory drugs. The analysis results show that in anti-inflammatory
effects, non-steroidal anti-inflammatory drugs can inhibit COX, induce the
cellular fatty acid desaturation and the changes of phospholipid components,
stimulate free fatty acids, activate calcium ion channels of endoplasmic
reticulum, and promote cell endocytosis, thus controlling inflammation and
activating cells. Non-steroidal anti-inflammatory drugs can promote endocytosis,
alter cell inflammatory response, and activate the process cells, thus realizing
the anti-inflammatory effects.
PMID- 26441062
TI - Joint involvement secondary to Epstein-Barr virus.
AB - We describe a group of patients with Epstein-Barr virus (EBV) infection and joint
involvement. Between February 2011 and January 2012, there were six cases in our
unit. Two presented with a pattern similar to rheumatoid arthritis, three had
polyarthralgia with an inflammatory pattern and only one patient had asymmetrical
oligoarthritis of large joints. They were all women aged between 25 and 75 (4
were of child-bearing potential). Diagnosis in all the cases was made by
exclusion of other possible causes and negative IgM were obtained for the rest of
the "Herpesviridae" family viruses. In our series, EBV joint involvement was more
common in women of childbearing potential. Clinical presentation was
heterogeneous but was predominantly in the form of inflammatory joint pain. When
it presents in the form of symmetrical polyarthritis, it can become chronic and
require the use of disease-modifying anti-rheumatic drugs.
PMID- 26441063
TI - Lavandula angustifolia and Lavandula latifolia Essential Oils from Spain:
Aromatic Profile and Bioactivities.
AB - Compositions of true lavender (Lavandula angustifolia) and spike lavender
(Lavandula latifolia) essential oils, cultivated and extracted in the Southeast
of Spain, were determined by gas chromatography coupled with mass spectrometry
detection, obtaining both relative (peak area) and absolute (using standard
curves) concentrations. Linalool (37-54 %), linalyl acetate (21-36 %) and (E)
beta-caryophyllene (1-3 %) were the most abundant components for L. angustifolia.
Linalool (35-51 %), eucalyptol (26-32 %), camphor (10-18 %), alpha-pinene (1-2
%), alpha-terpineol (1-2 %) and alpha-bisabolene (1-2 %) were the most abundant
components for L. latifolia. The characterization was completed with
enantioselective gas chromatography, in which the determined main molecules were
(-)-linalool, (-)-linalyl acetate and (+)-camphor. (S)-(-)-camphene, (R)-(+)
limonene, (1R, 9S)-(-)-(E)-beta-caryophyllene and (1R, 4R, 6R, 10S)-(-)
caryophyllene oxide were found in this study as the predominant enantiomers in
Spanish L. angustifolia. The characterised essential oils were tested for their
antioxidant activity against free radicals ABTS, DPPH, ORAC, chelating, and
reducing power. Inhibitory activity on lipoxygenase was observed indicating a
possible anti-inflammatory activity, mainly due to linalool, camphor, p-cymene
and limonene. These results can be the starting point for a future study of the
potential use of L. angustifolia and L. latifolia essential oils as natural
cosmetic and natural pharmaceutical ingredients for several skin diseases.
PMID- 26441064
TI - Sesquiterpene Lactones from Cynara cornigera: Acetyl Cholinesterase Inhibition
and In Silico Ligand Docking.
AB - Wild artichoke (Cynara cornigera), a thistle-like perennial belonging to the
Asteraceae family, is native to the Mediterranean region, northwestern Africa,
and the Canary Islands. While the pleasant, albeit bitter, taste of the leaves
and flowers is attributed to the sesquiterpene lactones cynaropicrin and cynarin,
a comprehensive phytochemical investigation still needs to be reported. In this
study seven sesquiterpene lactones were isolated from an aqueous methanol plant
extract, including a new halogenated metabolite (1), the naturally isolated
compound sibthorpine (2), and five metabolites isolated for the first time from
C. cornigera. Structures were established by spectroscopic methods, including
HREIMS, (1 )H, (13 )C, DEPT, (1 )H-(1 )H COSY, HMQC, and HMBC-NMR experiments as
well as by X-ray analysis. The isolated bioactive nutrients were analyzed for
their antioxidant and metal chelating activity. Compound 1 exhibited a potent
metal chelating activity as well as a high antioxidant capacity. Moreover, select
compounds were effective as acetyl cholinesterase inhibitors presenting the
possibility for such compounds to be examined for anti-neurodegenerative
activity. A computational pharmacophore elucidation and docking study was
performed to estimate the pharmacophoric features and binding conformation of
isolated compounds in the acetyl cholinesterase active site.
PMID- 26441065
TI - Review and Assessment of Medicinal Safety Data of Orally Used Echinacea
Preparations.
AB - Echinacea purpurea, Echinacea angustifoli and Echinacea pallida are frequently
used as medicinal plants. Besides asking for evidence on their efficacy, there is
an increasing interest for safety data. This review systematically presents the
available literature on drug interactions, contraindications, adverse events,
duration of use, and safety of use in pregnant and nursing women, and assesses
the safety profile of corresponding Echinacea preparations. It is noteworthy that
all safety data reported are as product specific as the pharmacological or
efficacy data are. In pharmacokinetic herb-drug interaction studies performed in
vivo, no significant inhibitions of human CYP2D6 and CYP3A4 isoforms have been
found after the administration of standardized E. purpurea preparations. However,
contradictory results exist in studies using liver microsomes. Adverse events
reported during clinical trials following administration of Echinacea spp. mono
preparations were generally mild and mostly without causality. Due to published
long term studies with continuous ingestion of different Echinacea preparations
up to 6 month with no reported toxicological concerns, Echinacea can be
recommended also for long-term use. Moreover, the contraindications in cases of
autoimmune diseases and immune-suppression are questionable, since lipophilic
Echinacea preparations containing alkamides suppress cellular immune responses,
and beneficial effects in autoimmunity were reported. The same applies for the
use during pregnancy. Although there has been some impact reported on embryonic
angiogenesis in mice, no association with an increased risk for major or minor
malformations during organogenesis was found in a literature review. Altogether,
the different evaluated Echinacea preparations are well-tolerated herbal
medicines in the management in children and adults alike.
PMID- 26441071
TI - Effect of Porcine Epidemic Diarrhea Virus Infectious Doses on Infection Outcomes
in Naive Conventional Neonatal and Weaned Pigs.
AB - Porcine epidemic diarrhea virus (PEDV) was identified in the United States (U.S.)
swine population for the first time in April 2013 and rapidly spread nationwide.
However, no information has been published regarding the minimum infectious dose
(MID) of PEDV in different pig models. The main objective of this study was to
determine the oral minimum infectious dose of PEDV in naive conventional neonatal
piglets and weaned pigs. A U.S. virulent PEDV prototype isolate
(USA/IN19338/2013) with known infectious titer was serially ten-fold diluted in
virus-negative cell culture medium. Dilutions with theoretical infectious titers
from 560 to 0.0056 TCID50/ml together with a medium control were orogastrically
inoculated (10ml/pig) into 7 groups of 5-day-old neonatal pigs (n = 4 per group)
and 7 groups of 21-day-old weaned pigs (n = 6 per group). In 5-day-old pigs, 10ml
of inoculum having titers 560-0.056 TCID50/ml, corresponding to polymerase chain
reaction (PCR) cycle threshold (Ct) values 24.2-37.6, resulted in 100% infection
in each group; 10ml of inoculum with titer 0.0056 TCID50/ml (Ct>45) caused
infection in 25% of the inoculated pigs. In 21-day-old pigs, 10ml of inoculum
with titers 560-5.6 TCID50/ml (Ct 24.2-31.4) resulted in 100% infection in each
group while 10ml of inoculum with titers 0.56-0.0056 TCID50/ml (Ct values 35.3
>45) did not establish infection in any pigs under study conditions as determined
by clinical signs, PCR, histopathology, immunohistochemistry, and antibody
response. These data reveal that PEDV infectious dose is age-dependent with a
significantly lower MID for neonatal pigs compared to weaned pigs. This
information should be taken into consideration when interpreting clinical
relevance of PEDV PCR results and when designing a PEDV bioassay model. The
observation of such a low MID in neonates also emphasizes the importance of
strict biosecurity and thorough cleaning/disinfection on sow farms.
PMID- 26441072
TI - Pricing a Protest: Forecasting the Dynamics of Civil Unrest Activity in Social
Media.
AB - Online social media activity can often be a precursor to disruptive events such
as protests, strikes, and "occupy" movements. We have observed that such civil
unrest can galvanize supporters through social networks and help recruit
activists to their cause. Understanding the dynamics of social network cascades
and extrapolating their future growth will enable an analyst to detect or
forecast major societal events. Existing work has primarily used structural and
temporal properties of cascades to predict their future behavior. But factors
like societal pressure, alignment of individual interests with broader causes,
and perception of expected benefits also affect protest participation in social
media. Here we develop an analysis framework using a differential game theoretic
approach to characterize the cost of participating in a cascade, and demonstrate
how we can combine such cost features with classical properties to forecast the
future behavior of cascades. Using data from Twitter, we illustrate the
effectiveness of our models on the "Brazilian Spring" and Venezuelan protests
that occurred in June 2013 and November 2013, respectively. We demonstrate how
our framework captures both qualitative and quantitative aspects of how these
uprisings manifest through the lens of tweet volume on Twitter social media.
PMID- 26441074
TI - A visualized probe method for localization of surface oxygen vacancy on TiO2: Au
in situ reduction.
AB - Surface oxygen vacancy has been investigated extensively due to its great
influence on photocatalysis in recent years. Among these investigations, the
location of surface defects is found to be a key factor during the photocatalytic
procedure. Especially when a crystal facet is involved, the synergistic action
between these two factors may greatly increase the photocatalytic efficiency.
Location of defects would greatly help in understanding the mechanism of this
coupling action. Without an available technique, however, it is very difficult to
gain the position information directly. In this paper, we provide a low-cost and
visualized method to solve this problem via in situ reduction of Au. TiO2 with
surface oxygen vacancy on a specific area is synthesized via a photochemical
reaction. Then the Au ion was reduced at the place where oxygen vacancy exists on
the TiO2 surface. Hence, the localization of surface vacancy will be determined
by examining the location of Au particles. Moreover, application of this method
can be extended to other surface defects such as oxygen vacancy on oxide
semiconductors, Ti(3+) in TiO2, Zn vacancy on ZnO, etc. This technique is helpful
for understanding how surface defects affect the properties of semiconductors.
PMID- 26441073
TI - Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle
Induced Periprosthetic Osteolysis in a Rat Model.
AB - We examined whether intermittent administration of parathyroid hormone [1-34]
(PTH[1-34]; 60 MUg/kg/day) can prevent the negative effects of titanium (Ti)
particles on implant fixation and periprosthetic osteolysis in a rat model.
Eighteen adult male rats (12 weeks old, bones still growing) received
intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group
received vehicle injections, and 12 rats from the control group and PTH treatment
group received Ti particle injections at the time of operation and intra
articular injections 2 and 4 weeks postoperatively. Six of the rats that received
Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks
postoperatively, all specimens were collected for assessment by X-ray, micro-CT,
biomechanical, scanning electron microscopy (SEM), and dynamic histomorphometry.
A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate
were observed in the control group compared to the blank group, demonstrating
that a periprosthetic osteolysis model had been successfully established.
Administration of PTH[1-34] significantly increased the bone mineral density of
the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation
strength in the PTH group compared to that in the control group. SEM revealed
higher bone-implant contact, thicker lamellar bone, and larger trabecular bone
area in the PTH group than in the control group. A higher mineral apposition rate
was observed in the PTH group compared to both the blank and control groups.
These findings imply that intermittent administration of PTH[1-34] prevents
periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34]
were evaluated at a suprapharmacological dosage to the human equivalent in rats;
therefore, additional studies are required to demonstrate its therapeutic
potential in periprosthetic osteolysis.
PMID- 26441075
TI - [Scoliosis update].
PMID- 26441076
TI - Do-not-resuscitate orders among advanced-stage Chinese lung cancer patients who
died in hospital.
AB - PURPOSE: Do-not-resuscitate (DNR) orders are an important part of end-of-life
care (EOL) for patients with incurable advanced lung cancer. The aim of this
study was to investigate the clinical factors related to the acceptance of DNR
orders by Chinese patients. METHODS: This study was a retrospective analysis
involving patients with advanced-stage (IIIB or IV) lung cancer who died in
hospital at our center from August 2004 through August 2014. The patients'
clinical characteristics and DNR forms were reviewed. RESULTS: Of the 348
patients enrolled, 260 (74.7 %) provided DNR orders signed only by surrogates.
The signing rate of DNR orders increased annually. The median interval from
signing a DNR order to death was 1 day (range, 0-72 days). Patients with poor
performance status (PS) (>=2) 1 week prior to death (OR, 3.395; 95 % CI, 1.536
7.502, P = 0.003) and relatively longer overall survival (OS) (>3 months) (OR,
2.464; 95 % CI, 1.566-4.472, P < 0.001) were more likely to sign DNR orders. CPR
was performed on 10.3 % (27/260) of patients with DNR orders, and was withheld in
22.7 % (20/88) of patients without DNR orders. CONCLUSIONS: The DNR order-signing
rate has been increasing annually among terminal patients with lung cancer in
China. DNR orders, all of which were signed by surrogates, were more likely to be
accepted by patients with slowly deteriorating disease and longer OS. More effort
should be taken to help patients and medical professionals establish a sensible
understanding of EOL care, including DNR orders, at earlier points during the
disease course.
PMID- 26441078
TI - Cancer rehabilitation and palliative care--two important parts of comprehensive
cancer care.
PMID- 26441077
TI - Malignancy associated hypercalcaemia-responsiveness to IV bisphosphonates and
prognosis in a palliative population.
AB - BACKGROUND: Hypercalcaemia is a potentially fatal paraneoplastic complication of
malignancy. It primarily manifests during the advanced phase of cancer, with the
life expectancy of patients ranging from weeks to months. The mainstay of
treatment is with bisphosphonates, but these are not frequently used in a
palliative population due to potential conflict with goals of care. GOAL: The
goals of this study was to determine the reversibility of hypercalcaemia amongst
patients whose underlying malignancy is not being treated and assess whether
correction results in improvement in symptoms attributable to hypercalcaemia,
while identifying risk factors that can predict responsiveness. METHODS: We
conducted a retrospective cohort study of 63 patients aged >18 years who were
admitted to the St Joseph's Palliative Care Unit, Australia between 2007 and
2013, having evidence of malignancy-associated hypercalcaemia which was treated
with bisphosphonates. We assessed the response to bisphosphonates based on
improvement of symptoms attributable to hypercalcaemia, as well as a reduction in
serum calcium. We used the Kaplan-Meier survival method and parametric survival
analysis to estimate the effect of the independent variables on time till death.
RESULTS: Thirty-six of sixty three patients achieved normocalcaemia following
treatment with an intravenous bisphosphonate. Complete response was influenced by
the number of instances of hypercalcaemia in the past and patient factors, such
as age and albumin levels. We found that a reduction in calcium level was
associated with a significantly prolonged survival, as well as symptomatic
improvement, irrespective of whether normocalcaemia was achieved. CONCLUSION: Our
study suggests that bisphosphonates can be recommended as a palliative measure
for selected patients to improve symptoms and prolong survival.
PMID- 26441079
TI - Tight junction defects are seen in the buccal mucosa of patients receiving
standard dose chemotherapy for cancer.
AB - PURPOSE: Oral mucositis is one of the most common and debilitating side effects
of chemotherapy treatment. Patients are often unable to eat and drink, which can
lead to poor clinical outcomes and extensive resource utilisation. The primary
aim of this study was to determine the molecular integrity of oral epithelial
tight junctions in patients undergoing chemotherapy. The secondary aim was to
correlate these changes with proinflammatory cytokines and matrix
metalloproteinase profiles. METHODS: Patients (n = 23) were recruited from the
Royal Adelaide Hospital between 2000 and 2003. Reach patient underwent two oral
buccal mucosa biopsies (4 mm): one prior to chemotherapy treatment and a second
one after chemotherapy treatment. Oral buccal mucosa biopsies were also taken
from seven healthy volunteers with no history of cancer, chemo- or radiotherapy
treatment or inflammatory disorders. Routine haematoxylin and eosin staining was
performed to determine epithelial thickness. Immunohistochemical staining was
performed for claudin-1, zonular occludens-1, occludin, interleukin-1beta, tumour
necrosis factor, interleukin-6, matrix metalloproteinase-2 and metalloproteinase
9. RESULTS: Patients receiving standard dose chemotherapy had significant
epithelial atrophy. Elevations in all cytokines and matrix metalloproteinases
were seen, with significant lamina propria staining for interleukin-6 and tumour
necrosis factor. Matrix metalloproteinase-2 appeared most upregulated within the
oral epithelium. These changes coincided with altered tight junction staining
properties. Changes in the staining intensity and localisation were both noted,
with clear cytoplasmic staining for zonular occludens-1 and claudin-1 in patients
treated with chemotherapy. CONCLUSIONS: Chemotherapy causes defects in oral tight
junctions, coupled with altered cytokine and matrix metalloproteinase profiles.
Tight junction disruption in the epithelium may contribute to ulcer development
or lead to poor tissue integrity, and the timing of these events may be a target
for preventative treatment.
PMID- 26441081
TI - Photophysics and Nonlinear Absorption of Gold(I) and Platinum(II) Donor-Acceptor
Donor Chromophores.
AB - A series of Au(I) and Pt(II) acetylide complexes of a pi-conjugated donor
acceptor-donor (D-A-D) chromophore were studied to develop quantitative structure
property relationships for their photophysical and nonlinear optical properties.
The D-A-D chromophore consists of a "TBT" unit, where T = 3-hexyl-2,5-thienylene
and BTD = 2,1,3-benzothiadiazole, capped with ethynylene groups. The D-A-D
chromophore is functionalized with Au(I)PR3 (R = -Me and -Ph) and trans
Pt(II)(PR3)2-CCPh (R = -Me and -Bu) "auxochromes". All of the metal complexes
were characterized by ground-state absorption, photoluminescence, nanosecond
transient absorption, and two-photon absorption (2PA) spectroscopy. The
experiments provided quantitative values of the photophysical parameters,
including rates for radiative decay and intersystem crossing (ISC), triplet
yields, and two-photon absorption cross sections. Pronounced solvatochromism in
the fluorescence spectra suggests an enhanced dipole moment in the excited state
of the complexes compared to the unmetalated TBT chromophore. The gold complexes
feature larger fluorescence quantum yields and longer emission lifetimes compared
to platinum. The Pt(II) complexes exhibit enhanced triplet-triplet absorption,
reduced triplet-state lifetimes, and larger singlet oxygen quantum yields,
consistent with more efficient ISC compared to the Au(I) complexes. When excited
by 100 fs pulses, all of the D-A-D chromophores exhibit moderate two-photon
absorption in the near-infrared between 700 and 900 nm. The 2PA cross section for
the Au(I) complexes is almost the same as the unmetalated D-A-D chromophore (~100
GM). The Pt(II) complexes exhibit significantly enhanced 2PA compared to the
other chromophores, reaching 1000 GM at 750 nm. Taken together, the results
indicate that the Pt(II) center is considerably more effective in inducing
singlet-triplet ISC and in enhancing the 2PA cross section. This result reveals
the greater promise for Pt(II) acetylides in chromophores for temporal and
frequency agile nonlinear absorption.
PMID- 26441082
TI - Clinical trials: Early phase clinical trials-are dose expansion cohorts needed?
PMID- 26441080
TI - New Insights into the Geographic Distribution of Mycobacterium leprae SNP
Genotypes Determined for Isolates from Leprosy Cases Diagnosed in Metropolitan
France and French Territories.
AB - BACKGROUND: Between 20 and 30 bacteriologically confirmed cases of leprosy are
diagnosed each year at the French National Reference Center for mycobacteria.
Patients are mainly immigrants from various endemic countries or living in French
overseas territories. We aimed at expanding data regarding the geographical
distribution of the SNP genotypes of the M. leprae isolates from these patients.
METHODOLOGY/PRINCIPAL FINDINGS: Skin biopsies were obtained from 71 leprosy
patients diagnosed between January 2009 and December 2013. Data regarding age,
sex and place of birth and residence were also collected. Diagnosis of leprosy
was confirmed by microscopic detection of acid-fast bacilli and/or amplification
by PCR of the M. leprae-specific RLEP region. Single nucleotide polymorphisms
(SNP), present in the M. leprae genome at positions 14 676, 1 642 875 and 2 935
685, were determined with an efficiency of 94% (67/71). Almost all patients were
from countries other than France where leprosy is still prevalent (n = 31) or
from French overseas territories (n = 36) where leprosy is not totally
eradicated, while only a minority (n = 4) was born in metropolitan France but
have lived in other countries. SNP type 1 was predominant (n = 33), followed by
type 3 (n = 17), type 4 (n = 11) and type 2 (n = 6). SNP types were concordant
with those previously reported as prevalent in the patients' countries of birth.
SNP types found in patients born in countries other than France (Comoros, Haiti,
Benin, Congo, Sri Lanka) and French overseas territories (French Polynesia,
Mayotte and La Reunion) not covered by previous work correlated well with
geographical location and history of human settlements. CONCLUSIONS/SIGNIFICANCE:
The phylogenic analysis of M. leprae strains isolated in France strongly suggests
that French leprosy cases are caused by SNP types that are (a) concordant with
the geographic origin or residence of the patients (non-French countries, French
overseas territories, metropolitan France) or (b) more likely random in regions
where diverse migration flows occurred.
PMID- 26441084
TI - Metabolic flux analysis of the halophilic archaeon Haladaptatus paucihalophilus.
AB - This work reports the (13)C-assisted metabolic flux analysis of Haladaptatus
paucihalophilus, a halophilic archaeon possessing an intriguing osmoadaption
mechanism. We showed that the carbon flow is through the oxidative tricarboxylic
acid (TCA) cycle whereas the reductive TCA cycle is not operative in H.
paucihalophilus. In addition, both threonine and the citramalate pathways
contribute to isoleucine biosynthesis, whereas lysine is synthesized through the
diaminopimelate pathway and not through the alpha-aminoadipate pathway.
Unexpected, the labeling patterns of glycine from the cells grown on [1
(13)C]pyruvate and [2-(13)C]pyruvate suggest that, unlike all the organisms
investigated so far, in which glycine is produced exclusively from the serine
hydroxymethyltransferase (SHMT) pathway, glycine biosynthesis in H.
paucihalophilus involves different pathways including SHMT, threonine aldolase
(TA) and the reverse reaction of glycine cleavage system (GCS), demonstrating for
the first time that other pathways instead of SHMT can also make a significant
contribution to the cellular glycine pool. Transcriptional analysis confirmed
that both TA and GCS genes were transcribed in H. paucihalophilus, and the
transcriptional level is independent of salt concentrations in the culture media.
This study expands our understanding of amino acid biosynthesis and provides
valuable insights into the metabolism of halophilic archaea.
PMID- 26441083
TI - Omeprazole induces NAD(P)H quinone oxidoreductase 1 via aryl hydrocarbon receptor
independent mechanisms: Role of the transcription factor nuclear factor erythroid
2-related factor 2.
AB - Activation of the aryl hydrocarbon receptor (AhR) transcriptionally induces phase
I (cytochrome P450 (CYP) 1A1) and phase II (NAD(P)H quinone oxidoreductase 1
(NQO1) detoxifying enzymes. The effects of the classical and nonclassical AhR
ligands on phase I and II enzymes are well studied in human hepatocytes.
Additionally, we observed that the proton pump inhibitor, omeprazole (OM),
transcriptionally induces CYP1A1 in the human adenocarcinoma cell line, H441
cells via AhR. Whether OM activates AhR and induces the phase II enzyme, NAD(P)H
quinone oxidoreductase 1 (NQO1), in fetal primary human pulmonary microvascular
endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM
will induce NQO1 in HPMEC via the AhR. The concentrations of OM used in our
experiments did not result in cytotoxicity. OM activated AhR as evident by
increased CYP1A1 mRNA expression. However, contrary to our hypothesis, OM
increased NQO1 mRNA and protein via an AhR-independent mechanism as AhR knockdown
failed to abrogate OM-mediated increase in NQO1 expression. Interestingly, OM
activated Nrf2 as evident by increased phosphoNrf2 (S40) expression in OM-treated
compared to vehicle-treated cells. Furthermore, Nrf2 knockdown abrogated OM
mediated increase in NQO1 expression. In conclusion, we provide evidence that OM
induces NQO1 via AhR-independent, but Nrf2-dependent mechanisms.
PMID- 26441085
TI - AKT-independent Reelin signaling requires interactions of heterotrimeric Go and
Src.
AB - Reelin, a large secreted extracellular matrix glycoprotein, plays a key role in
neuronal migration during cortical development and promotes neuronal maturation.
The signaling pathway regulating neuronal maturation in the postnatal period are
relatively less well understood. In this study, we demonstrated that a
heterotrimeric G protein, Go, is a novel target of Reelin-induced signaling to
promote neurite outgrowth. In primary hippocampal neurons of Reelin-deficient
reeler mice, neurite outgrowth was significantly reduced and rescued upon
addition of Reelin. Pertussis toxin (PTX) treatment or transfection with Galphao
siRNA suppressed Reelin-mediated neurite outgrowth in wild-type neurons.
Additionally, Reelin treatment led to increased phosphorylation of AKT, GSK3beta,
and JNK, which were all effectively blocked by the PI3K inhibitor, LY294002. By
comparison, PTX specifically blocked JNK activation, but not AKT and GSK3beta.
Immunoprecipitation assays disclosed that Reelin increases the active forms of
both Src and Galphao and promotes their direct association. Notably, Dab1, a
cytoplasmic adaptor molecule that mediates Reelin signaling, did not interact
with Galphao. Neurite outgrowth by Reelin was induced via activating Src kinase,
which directly stimulated Galphao, activity, leading to JNK activation. Based on
the collective findings, we suggest that Reelin-dependent signaling mechanisms
may be split into Src-AKT-dependent and Src-Go-dependent pathways. Our results
additionally provide evidence that Reelin receptors cross-communicate with
heterologous G protein-coupled receptors (GPCR) independently of the cognate
ligands of GPCR.
PMID- 26441086
TI - Replication of partial double-stranded RNAs by Qbeta replicase.
AB - Qbeta replicase, an RNA-dependent RNA polymerase of bacteriophage Qbeta, uses
single-stranded RNA as a template to synthesize the complementary strand. A
single-stranded RNA template may contain rigid secondary structures, such as long
stems, intermolecular double-stranded RNA regions. Presently, the effect of the
size of such double-stranded regions on the replication of RNA by Qbeta replicase
is unknown. In this study, we prepared RNA templates hybridized with
complementary RNA or DNA strands of various sizes and analyzed their replication
by Qbeta replicase. We found that Qbeta replicase synthesizes the complementary
strand as long as the template RNA is hybridized with no more than 200 nt
fragments, although the replication amounts were decreased. This is important
information to evaluate processivity of Qbeta replicase.
PMID- 26441088
TI - Discussion: Microbotox of the Lower Face and Neck: Evolution of a Personal
Technique and Its Clinical Effects.
PMID- 26441087
TI - Radiesse: Advanced Techniques and Applications for a Unique and Versatile
Implant.
AB - BACKGROUND: Radiesse is a well-tolerated facial injectable with unique filling
and lifting capabilities. Although initially approved for facial volumizing in
HIV-related lipodystrophy patients, it quickly gained wide acceptance for
aesthetic facial rejuvenation. In the USA, the Food and Drug Administration has
approved several new indications for its use. This synopsis presents the
experience and injection techniques currently favored by the primary author after
many years of use in thousands of patients. METHODS: The anecdotal practice of an
experienced injector is presented along with the current Food and Drug
Administration-approved standards of Radiesse injection. RESULTS: Radiesse has
many on- and off-label applications that can be thoughtfully incorporated into
clinical practice. Its unique chemical composition allows for immediate lifting
and filling with long-term collagen stimulation. The product can be reconstituted
to increase its versatility and minimize adverse events. Injections can be
performed in the supraperiosteal space and the subcutaneous layer and are best
administered in small, calculated doses to prevent nodules or vascular occlusion.
Various techniques for Radiesse injection in specific areas are discussed in
detail. CONCLUSIONS: Radiesse is a versatile injectable implant and a valuable
tool for short- and long-term cosmetic and reconstructive treatments. In addition
to various off-label uses, this injectable is often used in conjunction with
botox, other injectables, collagen stimulators and tightening devices. A
customized reconstitution of product increases its versatility for natural
appearing and long lasting results that are both economical and effective for
full facial rejuvenation.
PMID- 26441089
TI - Neurotoxins: Expanding Uses of Neuromodulators in Medicine--Headache.
AB - Over the course of the past 17 years, since the initial discovery of the
association between botulinum toxin-A (BT-A) and the reduction of headache
symptoms, the use of this neurotoxin has greatly evolved. BT-A has emerged as an
alternative to prophylactic pharmacological therapies in the prevention of
chronic migraine headaches, with an excellent safety profile and proven efficacy,
and is Food and Drug Administration-approved for on-label use since October 2010.
The mechanism of BT-A involves its effect at the neuromuscular junction,
inhibition of neuropeptide and neurotransmitter release in peripheral sensory
neurons, and retrograde axonal transport allowing for its direct effect on
inhibiting central sensitization. Through its diagnostic and therapeutic utility,
BT-A has proven to be an integral part in the treatment of chronic headache
disorders.
PMID- 26441090
TI - Neurotoxins: Expanding Uses of Neuromodulators in Medicine--Major Depressive
Disorder.
AB - BACKGROUND: Botulinum toxin A (BTA) is one of the most diversely used medications
of the 21st century and is now being researched as a treatment for major
depressive disorder (MDD). METHODS: The authors performed a literature search of
PubMed, Web of Science, and the Cochrane Register of Controlled Trials. The
primary investigators of the studies were contacted for additional unpublished
data. RESULTS: The authors identified 5 studies that met the criteria of using
BTA in the treatment of MDD. All studies showed significant reduction in
depressive symptoms with BTA injected into the glabellar muscles. In a pooled
analysis, botulinum toxin (n=59) vs placebo (n=75) had a -47% vs -16% reduction
in self-rated depression scores (P<0.0001) and a -46% vs -15% reduction in expert
rated depression scores (P<0.0001), respectively. Adverse reactions were mild
(temporary headaches and local irritation immediately after injection) and did
not differ between active group (13.6%) and placebo group (9.3%) (P=0.44).
CONCLUSIONS: Botulinum toxin injections in the glabellar frown muscles have been
associated with a significant improvement in depressive symptoms. Given the
prevalence of MDD, the promising results of preliminary trials, and the excellent
tolerability of this treatment intervention, larger studies are warranted.
PMID- 26441091
TI - Analysis of Facial Aesthetics as Applied to Injectables.
AB - Understanding the role of volume loss in the aging face has resulted in a
paradigm shift in facial rejuvenation techniques. Injectable materials for volume
restoration are among the most widespread cosmetic procedures performed. A new
approach to the aesthetics of facial aging is necessary to allow the greatest
improvement from volumetric techniques while maintaining natural appearing
results. Examining the face in terms of facial frames and facial shadows provides
the fundamental basis for our injectable analysis.
PMID- 26441092
TI - Introduction to Fillers.
AB - BACKGROUND: Over the last few years, injectable soft-tissue fillers have become
an integral part of cosmetic therapy, with a wide array of products designed to
fill lines and folds and revolumize the face. METHODS: This review describes
cosmetic fillers currently approved by the Food and Drug Administration and
discusses new agents under investigation for use in the United States. RESULTS:
Because of product refinements over the last few years-greater ease of use and
longevity, the flexibility of multiple formulations within one line of products,
and the ability to reverse poor clinical outcomes-practitioners have gravitated
toward the use of biodegradable agents that stimulate neocollagenesis for
sustained aesthetic improvements lasting up to a year or more with minimal side
effects. Permanent implants provide long-lasting results but are associated with
greater potential risk of complications and require the skilled hand of the
experienced injector. CONCLUSIONS: A variety of biodegradable and
nonbiodegradable filling agents are available or under investigation in the
United States. Choice of product depends on injector preference and the area to
be filled. Although permanent agents offer significant clinical benefits, modern
biodegradable fillers are durable and often reversible in the event of adverse
effects.
PMID- 26441093
TI - Current Concepts in the Use of Small-Particle Hyaluronic Acid.
AB - BACKGROUND: Soft-tissue augmentation with hyaluronic acid (HA) fillers has become
one of the most popular cosmetic procedures performed. HA fillers represent safe
and commonly used fillers. Several different HA fillers are available. The
differences lie in the manufacturing process, allowing for tailored uses. A small
particle HA with lidocaine (SP-HAL; Restylane Silk; Galderma, Uppsala, Sweden)
was approved by the US Food and Drug Administration in June 2014 but has been
available for many years in Canada as Restylane Fine Lines and in Europe as
Restylane Vital. METHODS: Relevant articles were reviewed relating to the
composition, effectiveness, and safety of SP-HAL. We also discuss the author's
extensive clinical experience in the use of this product in Canada. RESULTS: SP
HAL has demonstrated proven benefits for lip fullness, augmentation, and
treatment of perioral rhytides. Although off-label in the United States, SP-HAL
is also well suited for the treatment of superficial fine lines, including
periorbital, forehead, marionette, and smile lines. In addition, it has also been
used in the tear trough region. A novel application for SP-HAL includes use as a
skinbooster with intradermal micropuncture. In this technique, small aliquots of
product are injected so as to gradually rejuvenate the skin in areas such as the
face and hands. Side effects of SP-HAL were generally transient and mild. The
most common side effects were swelling, tenderness, bruising, pain, and redness.
CONCLUSION: SP-HAL is an effective and safe HA filler with varied clinical uses.
PMID- 26441094
TI - Current Concepts in the Use of Voluma, Volift, and Volbella.
AB - BACKGROUND: Hyaluronic acids (HAs) are very popular temporary fillers with a very
good safety record. Improvements and adaptations in clinical use are continuing.
METHODS: We have assessed the available literature to investigate the relatively
new Vycross technology that uses a mixture of high- and low-molecular-weight HAs
with a relatively low but varying HA concentration with enhanced cross-linking to
produce a number of products that have differing clinical indications. RESULTS:
Voluma has the highest HA concentration at 20 mg/mL, a high G prime translating
into lift capacity and cohesivity keeping the product capable to lift vertically
adding structure, form, and volume, whereas Volbella has much lower concentration
at 15 mg/mL, a lower G prime and cohesivity allowing it to be used in more a
horizontal spreading fashion enabling a superficial approach to lips, lines, and
more subtle depressions. Volift at 17.5 mg/mL HA is half way between the 2 other
products, allowing more subtle lift capacity but retaining an element of spread
making it a useful agent for the perioral region in general and in the treatment
of fine lines. CONCLUSION: A range of products has been released that allows
different components of facial structure, volume, and lines to be adequately
addressed.
PMID- 26441095
TI - Cohesive Polydensified Matrix Hyaluronic Acid for Fine Lines.
AB - BACKGROUND: Fine lines and crepey skin are dermal manifestations of multilevel,
age-related volume loss. It is, therefore, logical to combine intradermal
volumetry for fine lines with subcutaneous volumetry for contours. This
publication provides evidence- and experience-based rationales for application of
cohesive polydensified matrix hyaluronic acid filler (Belotero Balance). METHODS:
Evidence level II data demonstrate efficacy of this product and longevity for up
to a year or more with intradermal, superficial blanch injection. Its softness,
flow tendencies, and homogeneous tissue integration are informed by low
elasticity (G') and viscosity, high cohesivity, and high tan delta.
Ultrastructural analysis confirms variable-density cross-linking, intended to
confer resilience, and absence of detectable particles, minimizing Tyndall
effect. RESULTS: Scientific properties of Belotero Balance predict its 3
dimensional tissue expansion with prominent horizontal vectoring. We define this
as superficial flow volumetry. High cohesivity and resilience can maintain
structural integrity in typically mobile facial areas with strong muscular
forces, uneven pressure, and significant hyaluronidase activity. This facilitates
a natural appearance, both in repose and animation. CONCLUSIONS: Based on
available evidence and experience, cohesive polydensified matrix hyaluronic acid
is a notably efficacious fine line filler. The ideal fine line filler would
restore dermis structurally and dynamicaly-moving as one with it, efficaciously
expanding it, withstanding mechanical stress, swelling minimally, and potentially
stimulating collagenesis. The relative contributions of space-filling, water
binding, and collagenesis have implications for efficacy. A focus of current
research is to determine the impact of filler cohesivity and tissue integration
on these ideal qualities.
PMID- 26441096
TI - Current Concepts in the Use of Bellafill.
AB - As demonstrated by American Society of Plastic Surgeons statistics (2013),
patients seeking nonsurgical facial rejuvenation are increasing. A variety of
temporary and semipermanent soft-tissue fillers, such as hyaluronic acid, poly-L
lactic acid, and calcium hydroxylapatite, are readily available; however, they
have not been proven effective in treating facial acne scarring. Patient
tolerance for the inconvenience and repeat cost of short-term, temporary fillers
is waning as newer generation fillers with longer durations are coming on the
market. Permanent injectable fillers, such a Bellafill (Suneva Medical Inc., San
Diego, Calif.), represent a desirable solution for patients who want a long-term
result. With the recent Food and Drug Administration approval for the treatment
of moderate-to-severe, atrophic, distensible facial acne scars on the cheek(s) in
patients over the age of 21 years, Bellafill (polymethylmethacrylate collagen)
represents an effective solution for the treatment of facial acne scarring of the
face while maintaining an excellent safety profile.
PMID- 26441097
TI - Current Concepts in the Use of PLLA: Clinical Synergy Noted with Combined Use of
Microfocused Ultrasound and Poly-L-Lactic Acid on the Face, Neck, and
Decolletage.
AB - BACKGROUND: Aging of the face, neck, and decolletage is a multifactorial process
involving epidermal photodamage and loss of soft tissue and bony volume.
Multilevel rejuvenation of these areas can be obtained by enhancing volume
restoration, neocollagenesis, and tissue contraction with combined efficacy of
poly-L-lactic acid (PLLA) and microfocused ultrasound (MFU, Ultherapy)
treatments. METHODS: The authors reviewed the use of PLLA and MFUs as
collaborative modalities to improve the appearance of the face, neck, and
decolletage. RESULTS: Experienced cosmetic dermatology centers deliver PLLA and
MFU in a single session to target multiple tissue planes. CONCLUSIONS: Concurrent
treatment with PLLA and MFUs can be performed efficiently and safely; however,
additional research is needed to explore the synergistic effects of these
treatments. Patients may also benefit from decreased overall downtime and
necessary office visits.
PMID- 26441098
TI - Science of Hyaluronic Acid Beyond Filling: Fibroblasts and Their Response to the
Extracellular Matrix.
AB - Loss of viscoelasticity is one of the primarily signs of skin aging, followed by
appearance of visible wrinkles. Hyaluronic acid (HA)-based fillers are widely
used to fill wrinkles and compensate for volume loss. Recent clinical
observations demonstrate persistence of the filling effect longer than the
biological availability of the filler. Stimulation of new collagen by cross
linked HA and up-regulation of elastin have been suggested as possible
explanation to this observation and have been supported experimentally. Cross
linked HA substitutes for fragmented collagen in restoring extracellular matrix
required for normal activity of fibroblasts, such as collagen and elastin
production. To restore extracellular matrix efficiently, serial monthly
treatments are required. Boosting of facial and nonfacial skin through fibroblast
activation is a new indication for HA-based products. Injectable HA has also been
recently registered in Europe as agents specific for the improvement of skin
quality (Restylane Skinboosters). Further explanation of the possible mechanisms
supported by long-term clinical examples is presented herein.
PMID- 26441099
TI - Understanding, Avoiding, and Managing Severe Filler Complications.
AB - Any injectable filler may elicit moderate-to-severe adverse events, ranging from
nodules to abscesses to vascular occlusion. Fortunately, severe adverse events
are uncommon for the majority of fillers currently on the market. Because these
are rare events, it is difficult to identify the relevant risk factors and to
design the most efficacious treatment strategies. Poor aesthetic outcomes are far
more common than severe adverse events. These in contrast should be easily
avoidable by ensuring that colleagues receive proper training and follow best
practices.
PMID- 26441100
TI - The "Soft-Tissue Fillers and Neuromodulators: International and Multidisciplinary
Perspectives" Supplement.
PMID- 26441101
TI - Upper Face: Clinical Anatomy and Regional Approaches with Injectable Fillers.
AB - BACKGROUND: The use of facial fillers has been rapidly increased as the range of
injectable products and indications continues to expand. Complications may arise
from improper placement or technique. This article highlights the importance of
anatomic knowledge when using injectable fillers in the face. METHODS: A detailed
review of the clinical anatomy of the upper face is performed. Regional
approaches are described using the applied anatomy to efficiently and safely
augment the different subunits of the upper face. RESULTS: Key aspects of safe
and successful injection of fillers in the upper face include a thorough
knowledge of the location of fat compartments and neurovascular structures.
Awareness of these structures enables the practitioner to maximize injections,
while avoiding damage to important nerves and vessels. CONCLUSION: A detailed
knowledge of the anatomy and properties of the product is paramount to maximize
the efficacy while minimizing the risk of complications.
PMID- 26441103
TI - Ethnic and Gender Considerations in the Use of Facial Injectables: Asian
Patients.
AB - BACKGROUND: Asians have distinct facial characteristics due to underlying
skeletal and morphological features that differ greatly with those of whites.
This together with the higher sun protection factor and the differences in the
quality of the skin and soft tissue create a profound effect on their aging
process. Understanding of these differences and their effects in the aging
process in Asians is crucial in determining effective utilization and placement
of injectable products to ensure optimal aesthetic outcomes. METHODS: For younger
Asian women, the main treatment goal is to address the inherent structural
deficits through reshaping and the provision of facial support. Facial
injectables are used to provide anterior projection, to reduce facial width, and
to lengthen facial height. In the older group, the aim is for rejuvenation and
also to address the underlying structural issues that has compounded due to age
related volume loss. CONCLUSION: Asian women requesting cosmetic procedures do
not want to be Westernized but rather seeking to enhance and optimize their Asian
ethnic features.
PMID- 26441102
TI - Midface: Clinical Anatomy and Regional Approaches with Injectable Fillers.
AB - The clinical approach towards the midface is one of the most important
interventions for practitioners when treating age-related changes of the face.
Currently a plethora of procedures are used and presented. However, few of these
approaches have been validated or passed review board assigned evaluations.
Therefore, it is the aim of this work to establish a guideline manual for
practitioners for a safe and effective mid-face treatment based on the most
current concepts of facial anatomy. The latter is based on the 5-layered
structural arrangement and its understanding is the key towards the favoured
outcome and for minimizing complications.
PMID- 26441104
TI - Lower Face: Clinical Anatomy and Regional Approaches with Injectable Fillers.
AB - The use of injectable fillers enables facial sculpting through treatment of
volume depletion and modeling of facial contours. Injectable fillers are among
the most frequently performed minimally invasive cosmetic procedures.However,
treatment of the lower third of the face can be challenging and requires
expertise in facial anatomy. In this article, the authors provide a comprehensive
review of the anatomy of the lower third of the face, highlighting danger zones.
In addition, the authors describe their preferred approach and detailed technique
used in the treatment of each specific area, namely the jawline, prejowl sulcus,
melomental folds, and lips.
PMID- 26441105
TI - Hand: Clinical Anatomy and Regional Approaches with Injectable Fillers.
AB - BACKGROUND: Cosmetic physicians are more and more frequently asked for hand
rejuvenation. They commonly propose the same techniques as for the face. The
authors undertook an anatomical study of the hand dorsum to understand the
optimal location for an injected filler and to design the safest technique of
placement. METHODS: The first part of the study included dissections of 19 fresh
cadaveric hands and duplex ultrasounds investigation of 28 healthy hands. A
technique of injection specifically designed from anatomical findings was then
tested on 8 fresh cadaveric hands using magnetic resonance imaging and dissection
in comparison with 3 other commonly used techniques of rejuvenating injections.
RESULTS: Between the dermis and the tendons, the thickness of the fascial plane
was measured from 0.3 to 2.2 mm. Because of numerous fibrous septa, the entire
plane was found as a 3-dimensional sponge-like framework. Veins could be located
in all levels of this framework. There was no predefined free space. The optimal
place for the deposition of a filler was found to be the undersurface of the
dermis. The specific technique named Scrape Skin Threading Technique and using a
cannula scraping the deep side of the dermis was checked as the only technique
which could give a perfect placement of product restricted to the fascial layer.
CONCLUSION: The Scrape Skin Threading Technique was designed to inject safely and
accurately any kind of injectable in contact with the undersurface of the dermis,
which appeared anatomically as the optimal location of a filler for enhancing the
outer appearance of the dorsum of hands.
PMID- 26441106
TI - Decolletage: Regional Approaches with Injectable Fillers.
AB - BACKGROUND: Patients increasingly request rejuvenation of the aging and
photodamaged decolletage. Rhytides in this area can be addressed with injectables
such as poly-L-lactic acid and hyaluronic acid products and energy-based devices,
such as fractionated ablative and nonablative lasers and microfocused ultrasound
with visualization. METHODS: This article will review the anatomy of the chest
wall as it pertains to injectables that can be utilized in this area and
injection technique. A review of the literature and the authors' experience will
be discussed. CONCLUSION: Cosmetic injectables can be utilized safely and
effectively to improve the appearance of rhytides on the decolletage.
PMID- 26441107
TI - Ethnic and Gender Considerations in the Use of Facial Injectables: African
American Patients.
AB - The United States is becoming increasingly more diverse as the nonwhite
population continues to rise faster than ever. By 2044, the US Census Bureau
projects that greater than 50% of the US population will be of nonwhite descent.
Ethnic patients are the quickest growing portion of the cosmetic procedures
market, with African-Americans comprising 7.1% of the 22% of ethnic minorities
who received cosmetic procedures in the United States in 2014. The cosmetic
concerns and natural features of this ethnic population are unique and guided by
differing structural and aging processes than their white counterparts. As people
of color increasingly seek nonsurgical cosmetic procedures, dermatologists and
cosmetic surgeons must become aware that the Westernized look does not
necessarily constitute beauty in these diverse people. The use of specialized
aesthetic approaches and understanding of cultural and ethnic-specific features
are warranted in the treatment of these patients. This article will review the
key principles to consider when treating African-American patients, including the
average facial structure of African-Americans, the impact of their ethnicity on
aging and structure of face, and soft-tissue augmentation strategies specific to
African-American skin.
PMID- 26441108
TI - Ethnic and Gender Considerations in the Use of Facial Injectables: Latino
Patients.
AB - BACKGROUND: Globalization marks an important change in the world's perception of
elective procedures: patients are becoming consumers and cosmetic procedures are
being viewed as commodities. The quest to achieve and preserve a youthful
appearance has no geographic boundaries or ethnic limitations. Cosmetic
injectables have become an increasingly popular treatment option designed to
improve and preserve facial appearance. Hispanic (Latino) patients are one of the
rapidly increasing ethnic groups worldwide, seeking injectable treatments.
METHODS: The author evaluated the trends in the use of injectables in his
practice, mainly in Hispanic (Latino) patients, during one of the year's busiest
seasons, specifically December 2014. RESULTS: The results reflect Latino
patients' behavior toward injectables and how a high-volume injector addresses
the needs of patients, taking into consideration ethnic characteristics and
socioeconomic factors in balance with the provider plan for cosmetic improvement
or facial restoration. CONCLUSIONS: The author's Latino-Hispanic patients have
embraced the concept of "less invasive" facial rejuvenation, and in his
experience, he has found that their goal is to achieve precise results in a
natural manner. Ethnicity does not play a role in patients' behavior toward
cosmetic procedures. This "behavior" tends to be related more to the
socioeconomic status and/or the level of education, rather than ethnicity, which
move the patient toward specific procedures.
PMID- 26441109
TI - Ethnic and Gender Considerations in the Use of Facial Injectables: Male Patients.
AB - The contemporary male look includes sharp contours of the face with strong nose,
significant malar-midface structure, and a powerful chin with well-defined
jawline. Neurotoxins in the upper facial lines should preserve a lower position
of the brows and flatter arch in men. Excessive lifting of the eyebrows and full
correction of forehead and periorbital lines are not desirable. The use of dermal
fillers is fully accepted into the nasolabial. Male patients with sagginess and
hollowness related or not related to acquired lipodystrophies are candidates for
cheek correction with volumizers. Female attractiveness lies in the cheekbones,
and for men, it lies in the chin. The use of volumizers in the chin is very much
appreciated by male patients, especially when it is recessed. A strong and
masculine appearance is obtained by creating a square chin. Men present slight
thinner lips, especially the upper one. Lip reshape in male patients is very much
rejected. It requires expertise both in communication and in technical skills to
convince male patients to undergo lip treatments with fillers. The use of
injectables in male patients is growing. Neurotoxins in the upper facial lines
and the use of dermal fillers in the nasolabial folds are widely accepted. The
use of volumizers in the chin is highly appreciated. There is clear need of
volumizers in the cheek to correct sagginess and hollowness in men. However,
proper communication and technique are required. The same applies for the lips.
Cheek and lip reshape is still considered a taboo for most patients and
injectors.
PMID- 26441110
TI - Newer Understanding of Specific Anatomic Targets in the Aging Face as Applied to
Injectables: Aging Changes in the Craniofacial Skeleton and Facial Ligaments.
AB - Logical correction of aging contour changes of the face is based on understanding
its structure and the processes involved in the aging appearance. Aging changes
are seen at all tissue levels between the skin and bone although the relative
contribution of each component to the overall change of facial appearance has yet
to be satisfactorily determined. Significantly, the facial skeleton changes
profoundly with aging as a consequence of significant resorption of the bones of
dental origin in particular. The resultant loss of skeletal projection gives the
visual impression of descent while the reduced ligamentous support leads to
laxity of the overlying soft tissues. Understanding the specific changes of the
face with aging is fundamental to achieving optimum correction and safe use of
injectables for facial rejuvenation.
PMID- 26441111
TI - Newer Understanding of Specific Anatomic Targets in the Aging Face as Applied to
Injectables: Superficial and Deep Facial Fat Compartments--An Evolving Target for
Site-Specific Facial Augmentation.
AB - The identification of specific fat compartments of the face has greatly improved
the plastic surgeon's approach to facial rejuvenation. These superficial and deep
compartments are discretely partitioned into multiple independent units by
fascial barriers and undergo age-dependant volumetric changes. This knowledge has
created a topographical map allowing for the direct and precise augmentation of
those compartments that are deflated preferentially. These include the deep
medial cheek, nasolabial, superficial middle, and lateral cheek compartments.
Once this volume loss has been addressed, the overlying superficial
musculoaponeurotic system and skin envelope can be treated to address laxity and
bridge the compartments, creating a smooth cheek contour. Facial augmentation can
be performed alone in the correct patient; however, it most often complements
face-lifting. It is, therefore, important to have a thorough understanding of
this anatomy and the changes that occur during aging.
PMID- 26441113
TI - Newer Understanding of Specific Anatomic Targets in the Aging Face as Applied to
Injectables: Facial Muscles--Identifying Optimal Targets for Neuromodulators.
AB - The muscular anatomy of the face is complex. Animation patterns of facial muscles
vary significantly among individuals. Activity of facial muscles determines
expression and emotion and affects the eyes aperture and the amount and extent of
facial rhytids. Injection of botulin toxin for facial rejuvenation has become a
very popular procedure and allows the practitioner the ability to modulate facial
expression and to decrease the amount of facial rhytids. A thorough knowledge of
the variant facial anatomy is necessary to maximize the efficiency of botulin
toxin injection. This knowledge will also aid in minimizing complication an
untoward side effect.
PMID- 26441114
TI - Aesthetic Uses of Neuromodulators: Current Uses and Future Directions.
AB - BACKGROUND: The introduction of neuromodulators for aesthetic facial improvements
greatly expanded the limits of nonsurgical facial rejuvenation. Although many
current uses are considered "off-label," the widespread acceptance and favorable
safety profile of properly used botulinum toxins have made them one of the most
common aesthetic treatments available. METHODS: A literature review of current
facial aesthetic uses of various botulinum toxin preparations was done, and
general concepts were identified. RESULTS: Currently, Food and Drug
Administration-approved botulinum toxin preparations onabotulinumtoxinA (Botox),
abobotulinumtoxinA (Dysport), and incobotulinumtoxinA (Xeomin) have similar off
label indications and clinical uses. CONCLUSIONS: Although not considered
interchangeable, administration and clinical outcomes are not much different
between the 3 commonly used botulinum products. The impact of botulinum products
currently in development has yet to be determined.
PMID- 26441115
TI - Neurotoxins: Current Concepts in Cosmetic Use on the Face and Neck--Upper Face
(Glabella, Forehead, and Crow's Feet).
AB - There are 3 Food and Drug Administration-approved botulinum toxin formulations
now being successfully used for treatment in the upper face. The most common
areas for botulinum toxin treatment are the upper face, including the glabella,
forehead, brows, and lateral canthal lines or crow's feet. The frozen look is no
more desired in patients. Thus, physicians are more commonly individualizing
dosage based on the patient's variation in anatomy, muscle mass, asymmetry, and,
most importantly, desired outcome.
PMID- 26441116
TI - Neurotoxins: Current Concepts in Cosmetic Use on the Face and Neck--Lower Face.
AB - Botulinum toxin A was Food and Drug Administration approved in 2002 for the
temporary correction of glabellar frown lines. Since that time, a variety of
neuromodulators have established a convincing profile for both safety and
efficacy in the treatment hyperdynamic rhytides of the upper face. With
increasing clinical experience and expertise, these applications have been
expanded to include targeted treatment of muscles in both the mid and lower face.
This article details common techniques using botulinum toxin to treat orbicularis
oris, depressor anguli oris, mentalis, and masseter muscles for the temporary
correction of unwanted lower face hyperdynamic rhytides and facial contouring.
Although we detail our suggested quantity of units per injection site based on
onabotulinumtoxinA, all neuromodulators can be used in all of these suggested
treatment areas with adjustment of the quantity of units based on the efficacy of
the specific neuromodulator. A more compete discussion on the relative efficacy
of all neuromodulators is beyond the scope of this article.
PMID- 26441117
TI - Neurotoxins: Current Concepts in Cosmetic Use on the Face and Neck--Jawline
Contouring/Platysma Bands/Necklace Lines.
AB - The platysma muscle acts as a major depressor in the lower face with subsequent
inaesthetic implications. Botulinum toxin-A can be very useful to reverse some of
these and this chapter describes how to (1) sharpen the jawline with the
Nefertiti Lift, (2) treat anterior neck bands, and (3) soften necklace lines.
PMID- 26441118
TI - Anatomy of the Lower Face and Botulinum Toxin Injections.
AB - The use of botulinum toxin in the lower face is more complex and less reliable
than its use in the upper face. Use in the lower face is also fraught with more
adverse events. The anatomy of the lower face is complex, as the muscles of this
region are very close together and interface at different levels and depths to
perform heterogeneous functions, such as talking, eating, drinking, and
expressivity of the face. This article, based on the anatomical knowledge of each
muscle of the lower face, provides recommendations and guidelines to perform
botulinum toxin injection safely. The review of each muscle with its relevant
anatomy and relationship of this three-dimensional anatomy with the cutaneous
plane gives the exact position of injectable locations. For each muscle, the
number of points related to the motor end plate location and the exact dose
related to the muscular mass are indicated. Summary tables are provided.
PMID- 26441119
TI - Microbotox of the Lower Face and Neck: Evolution of a Personal Technique and Its
Clinical Effects.
AB - Microbotox is the injection of multiple microdroplets of diluted
onabotulinumtoxinA into the dermis or the interface between the dermis and the
superficial layer of facial muscles. The intention is to decrease sweat and
sebaceous gland activity to improve skin texture and sheen and to target the
superficial layer of muscles that find attachment to the undersurface of the
dermis causing visible rhytides. For treatment of the lower face and neck,
hundreds of microdroplets of diluted Botox are injected into the dermis or
immediate subdermal plane to improve skin texture, smoothen horizontal creases,
and decrease vertical banding of the neck, as well as to achieve better
apposition of the platysma to the jawline and neck, improving contouring of the
cervicomental angle. The Microbotox solution is mixed in the syringe by adding a
small volume of lidocaine to the calculated dose of onabotulinumtoxinA drawn from
a standard bottle of Botox prepared with 2.5 mL saline. Each 1 mL syringe of
Microbotox solution contains 20-28 units of onabotulinumtoxinA per mL of solution
and is used to deliver 100-120 injections. The lower face and neck will usually
require 1 mL per side. The injections are delivered intradermally using a 30- or
32-G needle raising a tiny blanched weal at each point. The author has over 1867
documented cases of Microbotox in various parts of the face (forehead, glabellar,
crow's-feet, infraorbital, and cheeks) and neck, the majority of these patients
being treated in forehead or the lower face and neck as described in this
article.
PMID- 26441120
TI - Introduction to "Soft-Tissue Fillers and Neuromodulators: International and
Multidisciplinary Perspectives".
PMID- 26441121
TI - In vitro screening of natural feed additives from crustaceans, diatoms, seaweeds
and plant extracts to manipulate rumen fermentation.
AB - BACKGROUND: Eight natural products from animal, unicellular algae, brown seaweed
and plant origins were chosen according to their theoretical antimicrobial
activity: Diatomaceous earths (DE), insoluble chitosan (ICHI), soluble chitosan
(CHI), seaweed meal (SWM), Ascophyllum nodosum (ASC), Laminaria digitata (LAM),
neem oil (NOIL) and an ivy fruit extract rich in saponins (IVY). Dose-response
incubations were conducted to determine their effect on rumen fermentation
pattern and gas production, while their anti-protozoal activity was tested using
(14) C-labelled bacteria. RESULTS: DE, SWM, NOIL and ICHI had very small effects
on rumen function when used at inclusion rate up to 2 g L(-1) . ASC had anti
protozoal effects (up to -23%) promoting a decrease in gas production and
methanogenesis (-15%). LAM increased VFA production (+7%) and shifted from
butyrate to acetate. CHI also shifted fermentation towards propionate production
and lower methane (-23%) and protozoal activity (-56%). IVY decreased protozoal
activity (-39%) and ammonia concentration (-56%), as well as increased feed
fermentation (+11% VFA concentration) and shifted from acetate to propionate
production. CONCLUSIONS: ASC, LAM, CHI and IVY showed promising potential in
vitro as feed additives to improve rumen function, thus more research is needed
to investigate their mode of action in the rumen microbial ecosystem. (c) 2015
Society of Chemical Industry.
PMID- 26441122
TI - Genotoxicity of commercial fungicide Cabrio Plus on human cell.
AB - Cabrio Plus, a commercial fungicide, is used in agriculture as the control agent
for a broad spectrum of diseases including black dot, early blight, late blight
and powdery mildew. This study aimed to evaluate the genotoxicity of commercial
formulation of Cabrio Plus which has been inadequately evaluated. The genotoxic
potential of Cabrio Plus in isolated human peripheral blood lymphocytes was
measured by means of an alkaline version of the comet assay (pH > 13) and in
whole blood by use of the in vitro micronucleus test. Cabrio Plus induced a
statistically significant increase in DNA damage assessed with the in vitro
micronucleus assay and the comet assay. Cabrio Plus also induced cytotoxicity in
a dose-dependent manner with the in vitro micronucleus assay. It can be concluded
that a commercially available pesticide formulation, Cabrio Plus, has the ability
to cause DNA damage and cytotoxicity.
PMID- 26441123
TI - Guided bone regeneration using resorbable membrane and different bone
substitutes: Early histological and molecular events.
AB - Bone insufficiency remains a major challenge for bone-anchored implants. The
combination of guided bone regeneration (GBR) and bone augmentation is an
established procedure to restore the bone. However, a proper understanding of the
interactions between the bone substitute and GBR membrane materials and the bone
healing environment is lacking. This study aimed to investigate the early events
of bone healing and the cellular activities in response to a combination of GBR
membrane and different calcium phosphate (CaP) materials. Defects were created in
the trabecular region of rat femurs, and filled with deproteinized bovine bone
(DBB), hydroxyapatite (HA) or strontium-doped HA (SrHA) or left empty (sham). All
the defects were covered with an extracellular matrix membrane. Defects were
harvested after 12h, 3d and 6d for histology/histomorphometry,
immunohistochemistry and gene expression analyses. Histology revealed new bone,
at 6d, in all the defects. Larger amount of bone was observed in the SrHA-filled
defect. This was in parallel with the reduced expression of osteoclastic genes
(CR and CatK) and the osteoblast-osteoclast coupling gene (RANKL) in the SrHA
defects. Immunohistochemistry indicated fewer osteoclasts in the SrHA defects.
The observations of CD68 and periostin-expressing cells in the membrane per se
indicated that the membrane may contribute to the healing process in the defect.
It is concluded that the bone-promoting effects of Sr in vivo are mediated by a
reduction in catabolic and osteoblast-osteoclast coupling processes. The
combination of a bioactive membrane and CaP bone substitute material doped with
Sr may produce early synergistic effects during GBR. STATEMENT OF SIGNIFICANCE:
The study provides novel molecular, cellular and structural evidence on the
promotion of early bone regeneration in response to synthetic strontium
containing hydroxyapatite (SrHA) substitute, in combination with a resorbable,
guided bone regeneration (GBR) membrane. The prevailing view, based mainly upon
in vitro data, is that the beneficial effects of Sr are exerted by the
stimulation of bone-forming cells (osteoblasts) and the inhibition of bone
resorbing cells (osteoclasts). In contrast, the present study demonstrates that
the local effect of Sr in vivo is predominantly via the inhibition of osteoclast
number and activity and the reduction of osteoblast-osteoclast coupling. This
experimental data will form the basis for clinical studies, using this material
as an interesting bone substitute for guided bone regeneration.
PMID- 26441124
TI - Surface nitridation improves bone cell response to melt-derived bioactive
silicate/borosilicate glass composite scaffolds.
AB - Novel bioactive amorphous glass-glass composite scaffolds (ICIE16/BSG) with
interconnected porosity have been developed. Hierarchically interconnected porous
glass scaffolds were prepared from a mixture of two melt-derived glasses: a
ICIE16 bioactive glass that was previously developed by Wu et al. (2011) to
prevent crystallization, and a borosilicate glass of composition 73.48 SiO2-11.35
B2O3-15.15 Na2O (wt%). The resulting melt derived glass-glass composite scaffolds
(ICIE16/BSG) were subject to surface functionalization to further improve its
interaction with biological systems. Surface functionalization was performed by a
nitridation process with hot gas N2/ammonia at 550 degrees C for 2h, obtaining
the ICIE16/BSG-NITRI. Evaluation of the degradation rate and the conversion to
hydroxyapatite after immersion in simulated body fluid predicted a good
biological activity of all the scaffolds, but particularly of the nitrided ones.
In vitro evaluation of osteoblastic cells cultured onto the nitrided and non
nitrided scaffolds showed cell attachment, proliferation and differentiation on
all scaffolds, but both proliferation and differentiation were improved in the
nitrided ICIE16/BSG-NITRI. STATEMENT OF SIGNIFICANCE: Biomaterials are often
required in the clinic to stimulate bone repair. We have developed a novel
bioglass (ICIE16/SBG-NITRI) that can be sintered into highly porous 3D scaffolds,
and we have further improved its bioactivity by nitridation. ICIE16/SBG-NITRI was
synthesized from a mixture of two melt-derived glasses through combined gel
casting and foam replication techniques, followed by nitridation. To mimic bone,
it presents high-interconnected porosity while being mechanically stable.
Nitridation improved its reactivity and bioactivity facilitating its resorption
and the deposition of apatite (bone-like mineral) on its surface and increasing
its degradation rate. The nitrided surface also improved the bioglass'
interaction with bone cells, which were found to attach better to ICIE16/SBG
NITRI and to differentiate earlier on its surface.
PMID- 26441125
TI - A materials perspective of Martyniaceae fruits: Exploring structural and
micromechanical properties.
AB - Several species of the plant family Martyniaceae are characterised by unique
lignified capsules with hook-shaped extensions that interlock with hooves and
ankles of large mammals to disperse the seeds. The arrangement of fruit endocarp
fibre tissues is exceptional and intriguing among plants. Structure-function
relationships of these slender, curved, but mechanically highly stressed fruit
extensions are of particular interest that may inspire advanced biomimetic
composite materials. In the present study, we analyse mechanical properties and
fracture behaviour of the hook-shaped fruit extensions under different load
conditions. The results are correlated with calculated stress distributions, the
specific cell wall structure, and chemical composition, providing a detailed
interpretation of the complex fruit tissue microstructure. At the cell wall
level, both a large microfibril angle and greater strain rates resulted in
Young's moduli of 4-9 GPa, leading to structural plasticity. Longitudinally
arranged fibre bundles contribute to a great tensile strength. At the tissue
level, transversely oriented fibres absorb radial stresses upon bending, whereas
cells encompass and pervade longitudinal fibre bundles, thus, stabilise them
against buckling. During bending and torsion, microcracks between axial fibre
bundles are probably spanned analogous to a circular anchor. Our study fathoms a
highly specialized plant structure, substantiating former assumptions about
epizoochory as dispersal mode. While the increased flexibility allows for proper
attachment of fruits during dynamical locomotion, the high strength and stability
prevent a premature failure due to heavy loads exerted by the animal.
PMID- 26441126
TI - The proangiogenic potential of a novel calcium releasing biomaterial: Impact on
cell recruitment.
AB - In current bone tissue engineering strategies the achievement of sufficient
angiogenesis during tissue regeneration is still a major limitation in order to
attain full functionality. Several strategies have been described to tackle this
problem, mainly by the use of angiogenic factors or endothelial progenitor cells.
However, when facing a clinical scenario these approaches are inherently complex
and present a high cost. As such, more cost effective alternatives are awaited.
Here, we demonstrate the potential of electrospun poly(lactic acid) (PLA) fiber
based membranes, containing calcium phosphate ormoglass (CaP) particles, to
elicit angiogenesis in vivo, in a subcutaneous model in mice. We show that the
current approach elicited the local expression of angiogenic factors, associated
to a chemotactic effect on macrophages, and sustained angiogenesis into the
biomaterial. As both PLA and CaP are currently accepted for clinical application
these off-the-shelf novel membranes have great potential for guided bone
regeneration applications. STATEMENT OF SIGNIFICANCE: In current bone tissue
engineering approaches the achievement of sufficient angiogenesis, during tissue
regeneration, is a major limitation in order to attain full tissue functionality.
Recently, our group has found that calcium ions released by the degradation of
calcium phosphate ormoglasses (CaP) are effective angiogenic promoters. Based on
this, in this work we successfully produced hybrid fibrous mats with different
contents of CaP nanoparticles and thus with different calcium ion release rates,
using an ormoglass - poly(lactic acid) blend approach. We show that these
matrices, upon implantation in a subcutaneous site, could elicit the local
expression of angiogenic factors, associated to a chemotactic effect on
macrophages, and sustained angiogenesis into the biomaterial, in a CaP dose
dependent manner. This off-the-shelf cost effective approach presents great
potential to translate to the clinics.
PMID- 26441127
TI - A glial cell line-derived neurotrophic factor delivery system enhances nerve
regeneration across acellular nerve allografts.
AB - Acellular nerve allografts (ANAs) are used clinically to bridge nerve gaps but
these grafts, lacking Schwann cells and therapeutic levels of neurotrophic
factors, do not support regeneration to the same extent as autografts. Here we
investigated a local drug delivery system (DDS) for glial cell line-derived
neurotrophic factor (GDNF) controlled release to implanted ANAs in rats using
drug-loaded polymeric microspheres (MSs) embedded in a fibrin gel. In a rat
hindlimb nerve gap model, a 10mm ANA was used to bridge a 5mm common peroneal
(CP) nerve gap. Experimental groups received DDS treatment at both suture sites
of the allografts releasing GDNF for either 2 weeks or 4 weeks. In negative
control groups, rats received no DDS treatment or empty DDS. Rats receiving nerve
isografts served as the positive control group. The numbers of motor and sensory
neurons that regenerated their axons in all the groups with GDNF MS and isograft
treatment were indistinguishable and significantly higher as compared to the
negative control groups. Nerve histology distal to the nerve graft demonstrated
increased axon counts and a shift to larger fiber diameters due to GDNF MS
treatment. The sustained delivery of GDNF to the implanted ANA achieved in this
study demonstrates the promise of this DDS for the management of severe nerve
injuries in which allografts are placed. STATEMENT OF SIGNIFICANCE: This work
addresses the common clinical situation in which a nerve gap is bridged using
acellular nerve allografts. However, these allografts are not as effective in
supporting nerve regeneration as the gold standard method of autografting. The
novel local drug delivery system used in this study provides sustained and
controlled release of glial cell line-derived neurotrophic factor (GDNF), one of
the most potent neurotrophic factors, which significantly improves nerve
regeneration following severe nerve injuries. Results from this research will
provide a mean of improving nerve allografts with locally delivered GDNF. This
strategy may lead to a novel "off the shelf" alternative to the current
management of severe nerve injuries.
PMID- 26441128
TI - Phage as versatile nanoink for printing 3-D cell-laden scaffolds.
AB - Bioprinting is an emerging technology for producing tissue-mimetic 3-D structures
using cell-containing hydrogels (bioink). Various synthetic and natural hydrogels
with key characteristics, including biocompatibility, biodegradability,
printability and crosslinkability, have been employed as ink materials in
bioprinting. Choosing the right cell-containing "bioink" material is the most
essential step for fabricating 3-D constructs with a controlled mechanical and
biochemical microenvironment that can lead to successful tissue regeneration and
repair. Here, we demonstrate that the genetically engineered M13 phage holds
great potential for use as a versatile nanoink for printing 3-D cell-laden
matrices. In particular, M13 phages displaying integrin-binding (GRGDS) and
calcium-binding (DDYD) domains on their surface were blended with alginate to
successfully form Ca(2+)-crosslinked hydrogels. Furthermore, 3-D cell-laden
scaffolds with high cell viability were generated after optimizing the printing
process. The MC3T3-E1 cells within these scaffolds showed enhanced proliferation
and differentiation rates that increased proportionally with the concentration of
phages in the 3-D matrices compared with the rates of cells in pure alginate
scaffolds. STATEMENT OF SIGNIFICANCE: Bioprinting is an emerging technology for
producing tissue-mimetic 3-D structures using cell-containing hydrogels called
bioink. Choosing the right bioink is essential for fabricating 3-D structures
with controlled mechanical and biochemical properties which lead to successful
tissue regeneration. Therefore, there is a growing demand for a new bioink
material that can be designed from molecular level. Here, we demonstrate that
genetically engineered M13 phage holds great potential for use as versatile
bioink. The phage-based bioink benefits from its replicability, self-assembling
property, and tunable molecular design and enables bioprinted scaffolds to
exhibit improved cell viability, proliferation and differentiation. This study
opens the door for the development of genetically tunable nanofibrous bioink
materials which closely mimic natural structural proteins in the extracellular
matrix.
PMID- 26441129
TI - Osteogenic differentiation and bone regeneration of iPSC-MSCs supported by a
biomimetic nanofibrous scaffold.
AB - Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) are a
new type of MSCs that come with attractive merits over the iPSCs per se. Aimed
for regenerating bone tissues, this study was designed to investigate osteogenic
differentiation and bone regeneration capacities of iPSC-MSCs by using biomimetic
nanofibers of hydroxyapatite/collagen/chitosan (HAp/Col/CTS). Murine iPSCs were
firstly induced to differentiate into iPSC-MSCs and thoroughly characterized.
Effects of HAp/Col/CTS nanofibers prepared from electrospinning of Col-doped
HAp/CTS nanocomposite, on osteogenic differentiation of the generated iPSC-MSCs
were then evaluated in detail, including cell morphology, proliferation,
migration, quantified specific osteogenic gene and protein expressions. Compared
with different controls (TCP, CTS, and HAp/CTS), the HAp/Col/CTS scaffold was
found to have more favorable effects on attachment and proliferation of iPSC-MSCs
than others (P<0.01). Expressions of osteogenic genes, Runx2, Ocn, Alp, and Col,
were significantly upregulated in iPSC-MSCs cultured on HAp/Col/CTS than CTS
(P<0.01). Similarly, there appeared considerably higher secreting activities of
osteogenesis protein markers, ALP and Col. Furthermore, mouse cranial defects
were created to investigate efficacy of using iPSC-MSCs in combination with
HAp/Col/CTS scaffold for regenerative bone repair in vivo. Examinations by
computed tomography (CT) imaging, bone mineral density and hematoxylin eosin (HE)
staining corroborated that cell-scaffold construct of iPSC-MSCs+HAp/Col/CTS could
effectively promote bone regeneration. After 6 weeks of implantation, bone
mineral density of the iPSC-MSCs+HAp/Col/CTS group was found to be nearly 2-fold
higher than others. Our results demonstrated that biomimetic nanofibers of
HAp/Col/CTS promoted the osteogenic differentiation and bone regeneration of iPSC
MSCs. The iPSC-MSCs+HAp/Col/CTS complex could be used as a new 'stem cell
scaffold' system for realizing personalized and efficacious bone regeneration in
future. STATEMENT OF SIGNIFICANCE: In bone tissue engineering, stem cells have
become the most important source of seed cells. iPSC-MSCs are a new type of MSCs
that come with attractive merits over the iPSCs per se. However, how to obtain
befitting iPSC-MSCs and regulate their osteogenic differentiation are the key
issues to be addressed. Given the great biomimicking capacity to extracellular
matrix, electrospun nanofibers may be explored to modulate osteogenic
differentiation of the iPSC-MSCs. This study successfully demonstrated that
biomimetic nanofibers of HAp/Col/CTS significantly promoted the osteogenic
differentiation and bone regeneration of iPSC-MSCs, which thereby suggests that
nanofibrous scaffold supported iPSC-MSCs complex may be a new 'stem cell
scaffold' system for regulating the fate of osteogenic differentiation of iPSC
MSCs towards patient-specific bone regeneration in future.
PMID- 26441130
TI - Comparative study of impact of hemodialysis and renal transplantation on
cognitive functions in ESRD patients.
AB - Cognitive impairment is defined as a newly appeared deficit in at least two areas
of cognitive functions, including disturbances in memory, executive functioning,
attention or speed of information processing, perceptual motor abilities, or
language. Cognitive impairment is highly prevalent in ESRD patients when compared
with the general population. It has also been associated with a decreased quality
of life. Cognitive functions in patients with ESRD showed improvement with
dialysis and renal transplantation. These findings illustrate the potential
importance of evaluating and comparing the effects of hemodialysis and
transplantation regarding cognitive performance and thus quality of life in ESRD
patients and normal subjects. This study was carried out in 100 patients (50 ESRD
patients on regular hemodialysis for at least 6 months and 50 post-transplant
patients who had maintained successful kidney graft for at least 3 months). All
patients underwent laboratory and psychometric scoring tests, including trail
making test part A, trail making test part B, digit span, and mini-mental state
examination. Thirty healthy adults matched by age and sex served as a control
group. The results showed significant differences in cognitive function tests
results between transplant and hemodialysis patients (P<0.01), suggesting that
transplant patients were superior in their cognitive performance, with the
correction of anemia being the most important factor for improving cognitive
performance in both groups. There were no significant differences between
transplant patients and control subjects in psychometric measures (P>0.05).
CONCLUSION: Renal transplantation as a modality of treatment, in ESRD patients,
is superior to hemodialysis in terms of cognitive performance improvement.
PMID- 26441131
TI - Low Levels of Dehydroepiandrosterone Sulfate in Younger Burnout Patients.
AB - OBJECTIVE: Dehydroepiandrosterone sulphate (DHEA-s) is an anabolic protective
hormone of importance for maintenance of health. DHEA-s levels peak in young
adults and decline thereafter with age. DHEA-s has previously been shown to be
lower in individuals reporting prolonged stress. This study investigates DHEA-s
levels in patients with clinical burnout, a disorder caused by long-term
psychosocial stress. METHODS: 122 patients (51% men) and 47 controls (51% men) in
the age 25-54 years were included in the study. DHEA-s levels were compared
between patients and controls in the whole sample and within each of the three 10
year-interval age groups. RESULTS: In the youngest age group (25-34 years), DHEA
s levels were on average 25% lower in the patients (p = 0.006). The differences
in DHEA-s levels between patients and controls were more pronounced among female
than male participants (on average 32% and 13% lower, respectively). There were
no differences in DHEA-s levels between patients and controls in the age group 35
44 years (p = 0.927) or 45-54 years (p = 0.897) or when analyzing all age groups
together (p = 0.187). CONCLUSION: The study indicates that levels of the health
promoting "youth" hormone DHEA-s are low in younger burnout patients. The fact
that younger adults have much higher DHEA-s levels and more pronounced inter
subject variability in DHEA-s levels than older individuals might explain why
burnout status differentiates patients from controls only among the youngest
patients included in this study.
PMID- 26441132
TI - Efficient Chemical Modification of Carbon Nanotubes with Metallacarboranes.
AB - As-produced single-walled carbon nanotubes (SWCNTs) tend to aggregate in bundles
due to pi-pi interactions. Several approaches are nowadays available to debundle,
at least partially, the nanotubes through surface modification by both covalent
and noncovalent approaches. Herein, we explore different strategies to afford an
efficient covalent functionalization of SWCNTs with cobaltabisdicarbollide
anions. Aberration-corrected HRTEM analysis reveals the presence of
metallacarboranes along the walls of the SWCNTs. This new family of materials
presents an outstanding water dispersibility that facilitates its processability
for potential applications.
PMID- 26441133
TI - Successful application of the DBLOC method to the hydroxylation of camphor by
cytochrome p450.
AB - The activation barrier for the hydroxylation of camphor by cytochrome P450 was
computed using a mixed quantum mechanics/molecular mechanics (QM/MM) model of the
full protein-ligand system and a fully QM calculation using a cluster model of
the active site at the B3LYP/LACVP*/LACV3P** level of theory, which consisted of
B3LYP/LACV3P** single point energies computed at B3LYP/LACVP* optimized
geometries. From the QM/MM calculation, a barrier height of 17.5 kcal/mol was
obtained, while the experimental value was known to be less than or equal to 10
kcal/mol. This process was repeated using the D3 correction for hybrid DFT in
order to investigate whether the inadequate treatment of dispersion interaction
was responsible for the overestimation of the barrier. While the D3 correction
does reduce the computed barrier to 13.3 kcal/mol, it was still in disagreement
with experiment. After application of a series of transition metal optimized
localized orbital corrections (DBLOC) and without any refitting of parameters,
the barrier was further reduced to 10.0 kcal/mol, which was consistent with the
experimental results. The DBLOC method to C?H bond activation in methane
monooxygenase (MMO) was also applied, as a second, independent test. The barrier
in MMO was known, by experiment, to be 15.4 kcal/mol. After application of the
DBLOC corrections to the MMO barrier compute by B3LYP, in a previous study, and
accounting for dispersion with Grimme's D3 method, the unsigned deviation from
experiment was improved from 3.2 to 2.3 kcal/mol. These results suggested that
the combination of dispersion plus localized orbital corrections could yield
significant quantitative improvements in modeling the catalytic chemistry of
transition-metal containing enzymes, within the limitations of the statistical
errors of the model, which appear to be on the order of approximately 2
kcal/mole.
PMID- 26441134
TI - Differential effects of stress on microglial cell activation in male and female
medial prefrontal cortex.
AB - Susceptibility to stress-linked psychological disorders, including post-traumatic
stress disorder and depression, differs between men and women. Dysfunction of
medial prefrontal cortex (mPFC) has been implicated in many of these disorders.
Chronic stress affects mPFC in a sex-dependent manner, differentially remodeling
dendritic morphology and disrupting prefrontally mediated behaviors in males and
females. Chronic restraint stress induces microglial activation, reflected in
altered microglial morphology and immune factor expression, in mPFC in male rats.
Unstressed females exhibit increased microglial ramification in several brain
regions compared to males, suggesting both heightened basal activation and a
potential for sex-dependent effects of stress on microglial activation.
Therefore, we assessed microglial density and ramification in the prelimbic
region of mPFC, and immune-associated genes in dorsal mPFC in male and female
rats following acute or chronic restraint stress. Control rats were left
unstressed. On the final day of restraint, brains were collected for either qPCR
or visualization of microglia using Iba-1 immunohistochemistry. Microglia in mPFC
were classified as ramified, primed, reactive, or amoeboid, and counted
stereologically. Expression of microglia-associated genes (MHCII, CD40, IL6,
CX3CL1, and CX3CR1) was also assessed using qPCR. Unstressed females showed a
greater proportion of primed to ramified microglia relative to males, alongside
heightened CX3CL1-CX3CR1 expression. Acute and chronic restraint stress reduced
the proportion of primed to ramified microglia and microglial CD40 expression in
females, but did not significantly alter microglial activation in males. This sex
difference in microglial activation could contribute to the differential effects
of stress on mPFC structure and function in males versus females.
PMID- 26441135
TI - Towards a blood-based diagnostic panel for bipolar disorder.
AB - BACKGROUND: Bipolar disorder (BD) is a costly, devastating and life shortening
mental disorder that is often misdiagnosed, especially on initial presentation.
Misdiagnosis frequently results in ineffective treatment. We investigated the
utility of a biomarker panel as a diagnostic test for BD. METHODS AND FINDINGS:
We performed a meta-analysis of eight case-control studies to define a diagnostic
biomarker panel for BD. After validating the panel on established BD patients, we
applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD,
75 pre-diagnostic schizophrenia and 90 first onset major depression disorder
(MDD) patients and 371 controls. The biomarker panel was identified using ten
fold cross-validation with lasso regression applied to the 87 analytes available
across the meta-analysis studies. We identified 20 protein analytes with
excellent predictive performance [area under the curve (AUC)?0.90]. Importantly,
the panel had a good predictive performance (AUC 0.84) to differentiate 12
misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good
predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD
patients and 184 controls. We also demonstrated the disease specificity of the
panel. CONCLUSIONS: An early and accurate diagnosis has the potential to delay or
even prevent the onset of BD. This study demonstrates the potential utility of a
biomarker panel as a diagnostic test for BD.
PMID- 26441137
TI - Proximity Driven Commensurate Pinning in YBa2Cu3O7 through All-Oxide Magnetic
Nanostructures.
AB - The design of artificial vortex pinning landscapes is a major goal toward large
scale applications of cuprate superconductors. Although disordered nanometric
inclusions have shown to modify their vortex phase diagram and to produce
enhancements of the critical current ( MacManus-Driscoll , J. L. ; Foltyn , S. R.
; Jia , Q. X. ; Wang , H. ; Serquis , A. ; Civale , L. ; Maiorov , B. ; Hawley ,
M. E. ; Maley , M. P. ; Peterson , D. E. Nat. Mater. 2004 , 3 , 439 - 443 and
Yamada , Y. ; Takahashi , K. ; Kobayashi , H. ; Konishi , M. ; Watanabe , T. ;
Ibi , A. ; Muroga , T. ; Miyata , S. ; Kato , T. ; Hirayama , T. ; Shiohara , Y.
Appl. Phys. Lett. 2005 , 87 , 1 - 3 ), the effect of ordered oxide nanostructures
remains essentially unexplored. This is due to the very small nanostructure size
imposed by the short coherence length, and to the technological difficulties in
the nanofabrication process. Yet, the novel phenomena occurring at oxide
interfaces open a wide spectrum of technological opportunities to interplay with
the superconductivity in cuprates. Here, we show that the unusual long-range
suppression of the superconductivity occurring at the interface between
manganites and cuprates affects vortex nucleation and provides a novel vortex
pinning mechanism. In particular, we show evidence of commensurate pinning in
YBCO films with ordered arrays of LCMO ferromagnetic nanodots. Vortex pinning
results from the proximity induced reduction of the condensation energy at the
vicinity of the magnetic nanodots, and yields an enhanced friction between the
nanodot array and the moving vortex lattice in the liquid phase. This result
shows that all-oxide ordered nanostructures constitute a powerful, new route for
the artificial manipulation of vortex matter in cuprates.
PMID- 26441138
TI - Covalent functionalization of N-doped graphene by N-alkylation.
AB - Nitrogen doped graphene was modified by N-alkylation using a combination of phase
transfer catalysis and microwave irradiation. The resulting derivatives of N
doped graphene were analysed showing that the bandgap of the material varied
depending on the alkylation agent used.
PMID- 26441136
TI - Assessing blood granulocyte colony-stimulating factor as a potential biomarker of
acute traumatic brain injury in mice and humans.
AB - Previous work has found that serum G-CSF was acutely elevated in mice 24h but not
one week after controlled cortical impact (CCI). The purpose of this study was to
investigate whether blood G-CSF correlates with the elevated brain cytokines in
mice after CCI and also if it correlates with traumatic brain injury (TBI) in
humans. Here, we found in mice undergoing CCI, a procedure that induces direct
injury to the brain, that serum G-CSF correlated directly or indirectly with
several brain cytokines, indicating it is a useful marker for the
neuroinflammation of TBI. A pilot study in humans (phase I, n=19) confirmed that
plasma G-CSF is acutely elevated on day 1 (p<0.001) of TBI and has returned to
baseline by one week. In a second human sample (phase II) (n=80), we found plasma
G-CSF peaks about 12h after arriving in the emergency department (41.6+/-5.4
pg/ml). Aging was weakly associated (p<0.05) with a less robust elevation in
serum G-CSF, but there was no difference with gender. ISS, a measure of total
severity of injury, correlated with the degree of elevation in serum G-CSF
(r=.419; p<0.05), but severity of head injury (via AIS) did not. The latter may
have been because of the statistically narrow range of head injuries among our
cases and the high number of cases diagnosed with closed head injury (a non
codable diagnosis). In conclusion, plasma G-CSF may be a useful biomarker of TBI,
correlating with neuroinflammation in the animal model and in the human studies
with time since injury and total severity of injury. As such, it may be useful in
determining whether TBI has occurred within the last 24h.
PMID- 26441139
TI - Monitoring the use of anatomical teaching material using a low-cost radio
frequency identification system: A comprehensive assessment.
AB - The correct tracking and monitoring of anatomical specimens is not only
imperative in any modern body donation programs but also in any universities for
which teaching the next generation of health care professionals is the primary
mission. This has long been an arduous process for anatomy institutions across
the world, and the recent focus of new curricula on self-directed learning adds
new stress on specimens which are used by students. The radio frequency
identification (RFID) technology has been proposed as a very effective tracking
system in healthcare considering that it enables automatic identification and
data capture of multiple items at once. In this study, the feasibility of a low
cost RFID inventory system is assessed, from its design to the performance of
commercially available RFID tags in a gross anatomy laboratory. The results show
that ultrahigh frequency-based RFID tags successfully performed when attached to
a collection of 112 plastinated and 280 wet dissected specimens. Comparison
analysis of different tags reveals, however, that careful selection of RFID tags
needs to be considered when wet specimens need to be tracked as preservation
fluids can absorb radio waves energy. This study demonstrates that it is
economically feasible to incorporate RFID technology to closely monitor the use
of anatomical teaching specimens. The described RFID inventory system was not
only able to preserve the integrity of the specimens being used by limiting
handling and therefore human error but was also able to identify missing or
misplaced specimens and to update their status.
PMID- 26441140
TI - Bladder Regeneration Using a Smart Acellular Collagen Scaffold with Growth
Factors VEGF, FGF2 and HB-EGF.
AB - Tissue engineering may become an alternative to current bladder augmentation
techniques. Large scaffolds are needed for clinically significant augmentation,
but can result in fibrosis and graft shrinkage. The purpose of this study was to
investigate whether smart acellular collagen-heparin scaffolds with growth
factors (GFs) VEGF, FGF2, and HB-EGF enhance bladder tissue regeneration and
bladder capacity in a large animal model of diseased bladder. Scaffolds of bovine
type I collagen with heparin and VEGF, FGF2, and HB-EGF measuring 3.2 cm in
diameter were prepared. In 23 fetal sheep, a bladder exstrophy was surgically
created at 79 days of gestation. One week after birth (at full term), the bladder
was reconstructed by primary closure (PC group) or using a collagen-heparin
scaffold with GFs (COLGF group) and compared to a historical group reconstructed
with a collagen scaffold without GFs (COL group). Functional (video urodynamics)
and histological evaluation was performed 1 and 6 months after bladder repair.
The overall survival rate was 57%. Cystograms were normal in all animals, except
for low-grade reflux in all groups. Urodynamics showed no statistically
significant differences in bladder capacity and compliance between groups.
Histological evaluation at 1 month revealed increased urothelium formation,
improved angiogenesis, and enhanced ingrowth of smooth muscle cells (SMCs) in the
COLGF group compared to the COL group. At 6 months, improved SMC ingrowth was
found in the COLGF group compared to the COL group; both scaffold groups showed
normal urothelial lining and standard extracellular matrix development. Bladder
regeneration using a collagen-heparin scaffold with VEGF, FGF2, and HB-EGF
improved bladder tissue regeneration in a large animal model of diseased bladder.
Larger GF-loaded constructs need to be tested to reach clinically significant
augmentation.
PMID- 26441141
TI - TREK1 channel blockade induces an antidepressant-like response synergizing with 5
HT1A receptor signaling.
AB - Current antidepressants often remain the inadequate efficacy for many depressive
patients, which warrant the necessary endeavor to develop the new molecules and
targets for treating depression. Recently, the two-pore domain potassium channel
TREK1 has been implicated in mood regulation and TREK-1 antagonists could be the
promising antidepressant. This study has screened a TREK1 blocker (SID1900) with
a satisfactory blood-brain barrier permeation and bioavailability.
Electrophysiological research has shown that SID1900 and the previously reported
TREK1 blocker (spadin) efficiently blocked TREK-1 current in HEK293 cells and
specifically blocked two-pore domain potassium channels in primary-cultured rat
hippocampal neurons. SID1900 and spadin induced a significant antidepressant-like
response in the rat model of chronic unpredictable mild stress (CUMS). Both two
TREK1 blockers substantially increased the firing rate of 5-HT-ergic neurons in
the dorsal raphe nuclei (DRN) and PFC of CUMS rats. SID1900 and spadin
significantly up-regulated the expression of PKA-pCREB-BDNF signaling in DRN,
hippocampus and PFC of CUMS rats, which were enhanced and reversed by a 5-HTR1A
agonist (8-OH-DPAT) and antagonist (WAY100635) respectively. The present findings
suggested that TREK1 channel blockers posses the substantial antidepressant-like
effect and have the potential synergistic effect with 5-HT1A receptor activation
through the common CREB-BDNF signal transduction.
PMID- 26441143
TI - Bacterial Genome Mining of Enzymatic Tools for Alkyne Biosynthesis.
AB - The alkyne is an important functionality widely used in material science,
pharmaceutical science, and chemical biology, but the importance of this
functionality is contrasted by the very limited number of enzymes known to be
involved in alkyne biosynthesis. We recently reported the first known carrier
protein-dependent pathway for terminal alkyne formation, and in silico analysis
suggested that this mechanism could be widespread in bacteria. In this paper, we
screened additional homologous gene cassettes presumed to be involved in alkyne
biosynthesis using both in vitro biochemical study and an E. coli-polyketide
synthase (PKS) reporting system for in vivo analysis. We discovered and
characterized a new terminal alkyne biosynthetic pathway comprised of TtuA, -B,
and -C from Teredinibacter turnerae T7901. While the acyl-CoA ligase homologue
(TtuA) demonstrated promiscuity in the activation and loading of medium-chain
fatty acids onto the carrier protein (TtuC), the desaturase homologue (TtuB)
showed stringent substrate specificity toward C10 fatty acyl moieties. In
addition, TtuB was demonstrated to be a bifunctional desaturase/acetylenase that
efficiently catalyzed two sequential O2-dependent dehydrogenation reactions. A
novel terminal-alkyne bearing polyketide was further produced upon coexpression
of ttuABC and a PKS gene in E. coli. The discovery and characterization of TtuA,
B, and -C provides us with a new bifunctional desaturase/acetylenase for
mechanistic and structural study and expands the scarce enzyme inventory for the
biosynthesis of the alkyne functionality, which has important applications in
synthetic and chemical biology.
PMID- 26441144
TI - Glucocorticoids Reduce Sepsis by Diminishing Dendritic Cell Responses.
AB - How does the body's immune system strike the delicate balance between under- and
over-response? A new study shows that glucocorticoids limit the production of the
proinflammatory cytokine interleukin-12 by dendritic cells in response to
invading bacteria, thereby helping to avoid sepsis. Read the Research Article.
PMID- 26441142
TI - CRF antagonism within the ventral tegmental area but not the extended amygdala
attenuates the anxiogenic effects of cocaine in rats.
AB - In addition to its initial rewarding effects, cocaine has been shown to produce
profound negative/anxiogenic actions. Recent work on the anxiogenic effects of
cocaine has examined the role of corticotropin releasing factor (CRF), with
particular attention paid to the CRF cell bodies resident to the extended
amygdala (i.e., the central nucleus of the amygdala [CeA] and the bed nucleus of
the stria terminalis [BNST]) and the interconnections within and projections
outside the region (e.g., to the ventral tegmental area [VTA]). In the current
study, localized CRF receptor antagonism was produced by intra-BNST, intra-CeA or
intra-VTA application of the CRF antagonists, D-Phe CRF(12-41) or astressin-B.
The effect of these treatments were examined in a runway model of i.v. cocaine
self-administration that has been shown to be sensitive to both the initial
rewarding and delayed anxiogenic effects of the drug in the same animal on the
same trial. These dual actions of cocaine are reflected in the development of an
approach-avoidance conflict ("retreat behaviors") about goal box entry that stems
from the mixed associations that subjects form about the goal. CRF antagonism
within the VTA, but not the CeA or BNST, significantly reduced the frequency of
approach-avoidance retreat behaviors while leaving start latencies (an index of
the positive incentive properties of cocaine) unaffected. These results suggest
that the critical CRF receptors contributing to the anxiogenic state associated
with acute cocaine administration may lie outside the extended amygdala, and
likely involve CRF projections to the VTA.
PMID- 26441145
TI - Cognitive-Motivational Influences on Health Behavior Change in Adults with
Chronic Pain.
AB - OBJECTIVE: The primary aim was to assess the psychological factors that influence
engagement in health behaviors in individuals with chronic pain using a new
measure, the Behavioral Engagement Test for Chronic Pain (BET-CP). A secondary
aim was to determine preliminary psychometric properties of the BET-CP. SUBJECTS:
Participants were 86 adults with chronic musculoskeletal pain recruited from
University of Florida pain clinics and the community. METHODS: Participants
completed a battery of self-report instruments online, including the BET-CP and
measures of related constructs. Items on the BET-CP assessed motivation, self
efficacy, outcome expectations, and the symptom benefit required to engage across
four health behaviors: exercise, diet, sleep, and pain self-management (e.g.,
relaxation and activity pacing). RESULTS: Participants reported modest
expectations of pain-related symptom improvement if they practiced the health
behaviors (22-26% improvement), but they required twice that (47-54% improvement)
to make it worth their while to commit to practicing them. Participants expected
to get the most symptom relief from relaxation and activity pacing, but they were
most confident and motivated to eat a healthy diet. In a subsample of
participants who provided data for psychometric analysis, the BET-CP demonstrated
strong test-retest reliability across 7 days and adequate convergent validity.
CONCLUSION: While patients with musculoskeletal pain have outcome expectancies
that are nearly in line with research on behavioral pain treatments, their
stringent requirements for symptom benefit may impede engagement in the health
behaviors recommended for their pain-related symptoms. Additional psychometric
study with larger sample sizes is needed to further validate the BET-CP.
PMID- 26441146
TI - Abnormal functional integration of thalamic low frequency oscillation in the BOLD
signal after acute heroin treatment.
AB - Heroin addiction is a severe relapsing brain disorder associated with impaired
cognitive control, including deficits in attention allocation. The thalamus has a
high density of opiate receptors and is critically involved in orchestrating
cortical activity during cognitive control. However, there have been no studies
on how acute heroin treatment modulates thalamic activity. In a cross-over,
double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were
studied after heroin and placebo administration, while 20 healthy controls were
included for the placebo condition only. Resting-state functional magnetic
resonance imaging was used to analyze functional integration of the thalamus by
three different resting state analysis techniques. Thalamocortical functional
connectivity (FC) was analyzed by seed-based correlation, while intrinsic
thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and
the fractional amplitude of low frequency fluctuations (fALFF). Relative to the
placebo treatment and healthy controls, acute heroin administration reduced
thalamocortical FC to cortical regions, including the frontal cortex, while the
reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal
pole were positively correlated with the plasma level of morphine, the main
psychoactive metabolite of heroin. Furthermore, heroin treatment was associated
with increased thalamic ReHo and fALFF values, whereas fALFF following heroin
exposure correlated negatively with scores of attentional control. The heroin
associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz)
oscillations. Our findings show that there are acute effects of heroin within the
thalamocortical system and may shed new light on the role of the thalamus in
cognitive control in heroin addiction. Future research is needed to determine the
underlying physiological mechanisms and their role in heroin addiction.
PMID- 26441147
TI - Phenotypic and functional changes in dermal primary fibroblasts isolated from
intrinsically aged human skin.
AB - Dermal fibroblasts play a key role in maintaining skin homoeostasis by
synthesizing and degrading extracellular matrix components. During ageing, they
are subjected to changes, such as the loss of type I collagen expression and an
increased synthesis of metalloproteinase I, leading to fragmentation of collagen
fibrils with consequent reduction of the mechanical tension and defects of skin
wound healing. Most information about fibroblast ageing was obtained from
experiments performed on replicative-senescent dermal fibroblasts in vitro.
However, the senescence status of fibroblasts isolated from intrinsically aged
skins and its consequences on functionality need to be deeper investigated.
Herein, we studied age-related phenotypic and functional alteration of
fibroblasts from 'young' (<35 years) and 'old' (>50 years) donors. Our results
brought evidence of the senescent status of 'old' fibroblasts by senescence
associated beta-galactosidase (SA-betagal) positive staining and p16 expression.
A PCR array focusing on senescence highlighted a subset of downregulated genes
including cell cycle progression and ECM genes in 'old' fibroblasts as well as a
subset of upregulated genes involved in senescence features. In 'old'
fibroblasts, we measured a downregulation of proliferative and contractile
capacities of migratory potential under PDGF stimulation and activation into
myofibroblasts under TGFbeta. Old fibroblasts were also more sensitive to
oxidative stress than 'young' ones. Of interest, downregulation of p16 expression
partially reversed the senescent phenotype of 'old' fibroblasts but failed to
restore their functional properties. In conclusion, our data brought evidence of
phenotypic and functional differences between fibroblasts from young and
intrinsically aged skin that may contribute to the alterations observed with
ageing.
PMID- 26441148
TI - Oligonucleotide Immobilization and Hybridization on Aldehyde-Functionalized
Poly(2-hydroxyethyl methacrylate) Brushes.
AB - DNA biosensing requires high oligonucleotide binding capacity interface
chemistries that can be tuned to maximize probe presentation as well as
hybridization efficiency. This contribution investigates the feasibility of
aldehyde-functionalized poly(2-hydroxyethyl methacrylate) (PHEMA) brush-based
interfaces for oligonucleotide binding and hybridization. These polymer brushes,
which allow covalent immobilization of oligonucleotides, are prepared by surface
initiated atom transfer radical polymerization (SI-ATRP) of HEMA followed by a
postpolymerization oxidation step to generate side chain aldehyde groups. A
series of polymer brushes covering a range of film thicknesses and grafting
densities was investigated with regard to their oligonucleotide binding capacity
as well as their ability to support oligonucleotide hybridization. Densely
grafted brushes were found to have probe oligonucleotide binding capacities of up
to ~30 pmol/cm(2). Increasing the thickness of these densely grafted brush films,
however, resulted in a decrease in the oligonucleotide binding capacity. Less
densely grafted brushes possess binding capacities of ~10 pmol/cm(2), which did
not significantly depend on film thickness. The oligonucleotide hybridization
efficiencies, however, were highest (93%) on those brushes that present the
lowest surface concentration of the probe oligonucleotide. These results
highlight the importance of optimizing the probe oligonucleotide surface
concentration and binding interface chemistry. The versatility and tunability of
the PHEMA-based brushes presented herein makes these films a very attractive
platform for the immobilization and hybridization of oligonucleotides.
PMID- 26441149
TI - Mouse Sensitivity is an Independent Risk Factor for Rhinitis in Children with
Asthma.
AB - BACKGROUND: Although mouse and cockroach allergy is known to be important in
urban children with asthma, the independent association of mouse and cockroach
sensitization with rhinitis in these children is unknown. OBJECTIVE: To determine
the association of mouse and cockroach sensitization with rhinitis in urban
children with asthma. METHODS: As part of the Mouse Allergen and Asthma
Intervention Trial, 499 urban children (5-17 years) with persistent asthma
underwent spirometry, skin prick testing to 14 common environmental allergens,
and serology for mouse-specific IgE. In 269 subjects, cockroach-specific IgE
serology was also obtained. Patient/parent-reported rhinitis in the last 2 weeks
and the last 1 year was the primary outcome measure. Mouse/cockroach exposure was
measured by reported frequency of sightings. Mouse allergen-settled bedroom dust
samples were also measured in mouse-sensitized children. RESULTS: Rhinitis was
reported in 49.9% and 70.2% of the participants within the last 2 weeks and the
last 1 year, respectively. Serum mouse IgE level of 0.35 IU/mL or more was
associated with rhinitis in the past 2 weeks (adjusted odds ratio, 2.15; 95% CI,
1.02-4.54; P = .04) and the past 1 year (adjusted odds ratio, 2.40; 95% CI, 1.12
5.1; P = .02) after controlling for age, race, sex, the presence of any smokers
at home, primary caregiver education level, number of allergen sensitivities,
cockroach IgE level of 0.35 IU/mL or more, and study site (Boston or Baltimore).
Measures of home mouse exposure were not associated with rhinitis, regardless of
mouse sensitivity. Cockroach sensitivity was not associated with rhinitis
regardless of sensitization to other allergens. CONCLUSIONS: In urban children
with asthma, increased mouse IgE, but not cockroach IgE, in the sera (mouse IgE
>= 0.35 IU/mL) may be associated independently with rhinitis.
PMID- 26441151
TI - An Electronic Asthma Self-Management Intervention for Young African American
Adults.
AB - BACKGROUND: Health disparities are seen in many chronic conditions including
asthma. Young African American adults represent a population at high risk for
poor asthma outcomes due to both their minority status and the difficult
transition from adolescence to adulthood. Recruitment and retention has been
challenging in this demographic stratum, and traditional asthma education is
often not feasible. OBJECTIVE: The objective of this study was to develop and
assess the feasibility of an electronic asthma self-management program for young
African American adults. METHODS: A total of 44 African American adults (age 18
30 years) with uncontrolled persistent asthma were enrolled in an asthma self
management program. The 6-week Breathe Michigan program (predicated on the social
cognitive theory) was tailored specifically to the concerns and preferences of
young African American adults. The entire program was completed electronically,
without any specialized human support. At 2 weeks and 3 months after program
completion, participants were contacted for follow-up. RESULTS: A total of 89% of
enrolled subjects completed the 6-week intervention, and 77% were available for
evaluation at 3 months. All subjects completing the 2-week postprogram survey
reported that the program was helpful, and 97% would recommend it to others.
Asthma control as measured by the Asthma Control Test improved from 16.1 to 19.3
(P < .01), and asthma quality of life as measured by the Mini Asthma Quality of
Life Questionnaire improved from 4.0 to 5.1 (P < .01). CONCLUSIONS: The Breathe
Michigan program is feasible for recruitment and retention, and demonstrated an
improvement in asthma control and quality of life for young African American
adults.
PMID- 26441150
TI - Persistent Food Allergy and Food Allergy Coexistent with Eczema Is Associated
with Reduced Growth in the First 4 Years of Life.
AB - BACKGROUND: Food allergy has been associated with lower weight and height in
cross-sectional studies in children; however, this has not been investigated in
longitudinal studies to explore growth over time, and previous studies have not
accounted for coexisting eczema. OBJECTIVE: The objective of this study was to
examine the association of IgE-mediated food allergy and eczema with
anthropometric measures at 1 and 4 years of age. METHODS: In the HealthNuts
population-based cohort, infants recruited at age 1 year underwent a skin prick
test to egg, peanut, and sesame; those sensitized had oral food challenges. Food
challenges repeated at 4 years determined food allergy persistence or resolution.
Eczema was defined as parent report of eczema diagnosis. Parent-reported weight
and height and child health record data were used to calculate age- and sex
adjusted percentiles from World Health Organization charts. Multivariable linear
regression models were fitted to examine the effect of food allergy and eczema on
weight and height controlling for potential confounders. RESULTS: Children with
both food allergy and eczema at age 1 had lower percentiles for mean weight (51.3
vs 58.3 percentile, P = .001) and height (48.4 vs 53.4, P = .028) at age 1
compared with those with neither condition. There was no difference for children
with only food allergy or eczema at age 1. By age 4, children with persistent
food allergy and persistent eczema, but not those with resolved food allergy,
were still shorter and lighter. CONCLUSIONS: Children with both food allergy and
eczema were shorter and lighter throughout early childhood, with more pronounced
differences in those with persistent food allergy.
PMID- 26441152
TI - A case of IgG4-related bronchial disease successfully treated with inhaled
corticosteroids.
PMID- 26441153
TI - Evidence for polymorphism in the cytochrome P450 2D50 gene in horses.
AB - Metabolism is an essential factor in the clearance of many drugs and as such
plays a major role in the establishment of dosage regimens and withdrawal times.
CYP2D6, the human orthologue to equine CYP2D50, is a drug-metabolizing enzyme
that is highly polymorphic in humans leading to widely differing levels of
metabolic activity. As CYP2D6 is highly polymorphic, in this study it was
hypothesized that the gene coding for the equine orthologue, CYP2D50, may also be
prone to polymorphism. Blood samples were collected from 150 horses, the CYP2D50
gene was cloned and sequenced; and full-length sequences were analyzed for single
nucleotide polymorphisms (SNPs), deletions, or insertions. Pharmacokinetic data
were collected from a subset of horses following the administration of a single
oral dose of tramadol and probit analysis used to calculate metabolic ratios.
Prior to drug administration, the ability of recombinant CYP2D50 to metabolize
tramadol to O-desmethyltramadol was confirmed. Sequencing of CYP2D50 identified
126 exonic SNPs, with 31 of those appearing in multiple horses. Oral
administration of tramadol to a subset of these horses revealed variable
metabolic ratios (tramadol: O-desmethyltramadol) in individual horses and
separation into three metabolic groups. While a limited number of horses of
primarily a single breed were studied, the variability in tramadol metabolism to
O-desmethyltramadol between horses and preliminary evidence of what appears to be
poor, extensive, and ultra-rapid metabolizers supports further study of the
potential for genetic polymorphisms in the CYP2D50 gene in horses.
PMID- 26441154
TI - Protein structure refinement with adaptively restrained homologous replicas.
AB - A novel protein refinement protocol is presented which utilizes molecular
dynamics (MD) simulations of an ensemble of adaptively restrained homologous
replicas. This approach adds evolutionary information to the force field and
reduces random conformational fluctuations by coupling of several replicas. It is
shown that this protocol refines the majority of models from the CASP11
refinement category and that larger conformational changes of the starting
structure are possible than with current state of the art methods. The
performance of this protocol in the CASP11 experiment is discussed. We found that
the quality of the refined model is correlated with the structural variance of
the coupled replicas, which therefore provides a good estimator of model quality.
Furthermore, some remarkable refinement results are discussed in detail. Proteins
2016; 84(Suppl 1):302-313. (c) 2015 Wiley Periodicals, Inc.
PMID- 26441155
TI - Neural Correlates of the Propensity for Retaliatory Behavior in Youths With
Disruptive Behavior Disorders.
AB - OBJECTIVE: Youths with disruptive behavior disorders (DBD) (conduct disorder and
oppositional defiant disorder) have an elevated risk for maladaptive reactive
aggression. Theory suggests that this is due to an elevated sensitivity of basic
threat circuitry implicated in retaliation (amygdala/periaqueductal gray) in
youths with DBD and low levels of callous-unemotional traits and dysfunctional
regulatory activity in the ventromedial prefrontal cortex in youths with DBD
irrespective of callous-unemotional traits. METHOD: A total of 56 youths 10-18
years of age (23 of them female) participated in the study: 30 youths with DBD,
divided by median split into groups with high and low levels of callous
unemotional traits, and 26 healthy youths. All participants completed an
ultimatum game task during functional MRI. RESULTS: Relative to the other groups,
youths with DBD and low levels of callous-unemotional traits showed greater
increases in activation of basic threat circuitry when punishing others and
dysfunctional down-regulation of the ventromedial prefrontal cortex during
retaliation. Relative to healthy youths, all youths with DBD showed reduced
amygdala-ventromedial prefrontal cortex connectivity during high provocation.
Ventromedial prefrontal cortex responsiveness and ventromedial prefrontal cortex
amygdala connectivity were related to patients' retaliatory propensity
(behavioral responses during the task) and parent-reported reactive aggression.
CONCLUSIONS: These data suggest differences in the underlying neurobiology of
maladaptive reactive aggression in youths with DBD who have relatively low levels
of callous-unemotional traits. Youths with DBD and low callous-unemotional traits
alone showed significantly greater threat responses during retaliation relative
to comparison subjects. These data also suggest that ventromedial prefrontal
cortex-amygdala connectivity is critical for regulating retaliation/reactive
aggression and, when dysfunctional, contributes to reactive aggression,
independent of level of callous-unemotional traits.
PMID- 26441156
TI - Reproductive Safety of Second-Generation Antipsychotics: Current Data From the
Massachusetts General Hospital National Pregnancy Registry for Atypical
Antipsychotics.
AB - OBJECTIVE: Second-generation antipsychotics are used to treat a spectrum of
psychiatric illnesses in reproductive-age women. The National Pregnancy Registry
for Atypical Antipsychotics was established to determine the risk of major
malformations among infants exposed to second-generation antipsychotics during
pregnancy relative to a comparison group of unexposed infants of mothers with
histories of psychiatric morbidity. METHOD: Women were prospectively followed
during pregnancy and the postpartum period; obstetric, labor, delivery, and
pediatric medical records were obtained. Eligible enrollees were pregnant women
ages 18-45. The Registry is based at the Center for Women's Mental Health at
Massachusetts General Hospital. Women were recruited through provider referral,
self-referral, and the Center's web site. RESULTS: As of December 2014, 487 women
were enrolled: 353 who used second-generation antipsychotics and 134 comparison
women. Medical records were obtained for 82% of participants. A total of 303
women had completed the study and were eligible for inclusion in the analysis. Of
214 live births with first-trimester exposure to second-generation
antipsychotics, three major malformations were confirmed. In the control group
(N=89), one major malformation was confirmed. The absolute risk of major
malformations was 1.4% for exposed infants and 1.1% for unexposed infants. The
odds ratio for major malformations comparing exposed infants with unexposed
infants was 1.25 (95% CI=0.13-12.19). CONCLUSIONS: The results suggest that it
would be unlikely for second-generation antipsychotics to raise the risk of major
malformations more than 10-fold beyond that observed in the general population or
among control groups using other psychotropic medications. If the estimate
stabilizes around the null with ongoing data collection, findings may be
reassuring for both clinicians and women trying to make risk-benefit treatment
decisions about using atypical antipsychotics during pregnancy. These findings
are timely given the renewed focus of regulatory agencies on reproductive safety.
PMID- 26441158
TI - Pattern of Drug Use and Associated Behaviors Among Female Injecting Drug Users
From Northeast India: A Multi-Centric, Cross-Sectional, Comparative Study.
AB - BACKGROUND: Studies from developed countries document the presence of injecting
drug use among females and significantly higher vulnerabilities and risks as
compared with male injecting drug users (IDUs). Studies comparing vulnerabilities
and drug use patterns between female and male IDUs are not available for
developing countries. OBJECTIVES: The aim of the study was to assess the drug use
pattern and related HIV vulnerabilities among female IDUs and compare these
findings with those from male IDUs from four states of Northeast India. METHOD:
The study used data collected as part of a nationwide study of drug use pattern
and related HIV vulnerabilities among IDUs. Ninety-eight female and 202 male IDUs
accessing services from harm reduction sites across the four states of Northeast
region of India were chosen through random sampling methodology. Drug use
pattern, injecting practices, and knowledge of HIV were assessed using a
structured questionnaire. RESULTS: Significantly higher proportion of female IDUs
was uneducated, unemployed, reported their occupation as sex workers, and
switched to injecting drug use faster as compared with male IDUs. Female IDUs
practicing sex work differed significantly from those who did not with respect to
frequency of daily injections, choice of drugs injected, and concomitant use of
non-injecting drugs. More than half of female IDUs initiated sharing within the
first month of injecting. CONCLUSIONS: The study demonstrates that female IDUs
differ from male IDUs in their drug use pattern, initiation into injection as
well as injecting behavior, which would be an important consideration during
designing of female-specific interventions.
PMID- 26441157
TI - Gating Deficit Heritability and Correlation With Increased Clinical Severity in
Schizophrenia Patients With Positive Family History.
AB - OBJECTIVE: The Consortium on the Genetics of Schizophrenia Family Study evaluated
12 primary and other supplementary neurocognitive and neurophysiological
endophenotypes in schizophrenia probands and their families. Previous analyses of
prepulse inhibition (PPI) and P50 gating measures in this sample revealed
heritability estimates that were lower than expected based on earlier family
studies. Here the authors investigated whether gating measures were more
heritable in multiply affected families with a positive family history compared
with families with only a single affected proband (singleton). METHOD: A total of
296 nuclear families consisting of a schizophrenia proband, at least one
unaffected sibling, and both parents underwent a comprehensive endophenotype and
clinical characterization. The Family Interview for Genetic Studies was
administered to all participants and used to obtain convergent psychiatric
symptom information for additional first-degree relatives. Among the families, 97
were multiply affected, and 96 were singletons. RESULTS: Both PPI and P50 gating
displayed substantially increased heritability in the 97 multiply affected
families (47% and 36%, respectively) compared with estimates derived from the
entire sample of 296 families (29% and 20%, respectively). However, no evidence
for heritability was observed for either measure in the 96 singleton families.
Schizophrenia probands derived from the multiply affected families also displayed
a significantly increased severity of clinical symptoms compared with those from
singleton families. CONCLUSIONS: PPI and P50 gating measures demonstrate
substantially increased heritability in schizophrenia families with a higher
genetic vulnerability for illness, providing further support for the commonality
of genes underlying both schizophrenia and gating measures.
PMID- 26441159
TI - Food insecurity, overweight and obesity among low-income African-American
families in Baltimore City: associations with food-related perceptions.
AB - OBJECTIVE: To examine associations between food insecurity, excess body weight,
psychosocial factors and food behaviours among low-income African-American
families. DESIGN: Cross-sectional survey of participants in the baseline
evaluation of the B'More Healthy Communities for Kids (BHCK) obesity prevention
trial. We collected data on socio-economic factors, food source destinations,
acquiring food, preparation methods, psychosocial factors, beliefs and attitudes,
participation in food assistance programmes, anthropometry and food security. We
used principal component analysis to identify patterns of food source
destinations and logistic regression to examine associations. SETTING: Fourteen
low-income, predominantly African-American neighbourhoods in Baltimore City, MD,
USA. SUBJECTS: Two hundred and ninety-eight adult caregiver-child (10-14 years
old) dyads. RESULTS: Of households, 41.6 % had some level of food insecurity and
12.4 % experienced some level of hunger. Food-insecure participants with hunger
were significantly more likely to be unemployed and to have lower incomes. We
found high rates of excess body weight (overweight and obesity) among adults and
children (82.8 % and 37.9 % among food insecure without hunger, 89.2 % and 45.9 %
among food insecure with hunger, respectively), although there were no
significant differences by food security status. Food source usage patterns, food
acquisition, preparation, knowledge, self-efficacy and intentions did not differ
by food security. Food security was associated with perceptions that healthy
foods are affordable and convenient. Greater caregiver body satisfaction was
associated with food insecurity and excess body weight. CONCLUSIONS: In this
setting, obesity and food insecurity are major problems. For many food-insecure
families, perceptions of healthy foods may serve as additional barriers to their
purchase and consumption.
PMID- 26441161
TI - Feasibility of Ionization-Mediated Pathway for Ultraviolet-Induced Melanin
Damage.
AB - Melanin is the pigment found in human skin that is responsible for both
photoprotection and photodamage. Recently there have been reports that greater
photodamage of DNA occurs when cells containing melanin are irradiated with
ultraviolet (UV) radiation, thus suggesting that the photoproducts of melanin
cause DNA damage. Photoionization processes have also been implicated in the
photodegradation of melanin. However, not much is known about the oxidation
potential of melanin and its monomers. In this work we calculate the ionization
energies of monomers, dimers, and few oligomers of eumelanin to estimate the
threshold energy required for the ionization of eumelanin. We find that this
threshold is within the UV-B region for eumelanin. We also look at the charge and
spin distributions of the various ionized states of the monomers that are formed
to understand which of the ionization channels might favor monomerization from a
covalent dimer.
PMID- 26441163
TI - Insurers Again at Odds With Hospitals and Physicians.
PMID- 26441160
TI - Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate
Cancer: A Meta-analysis.
AB - Despite the increasing number of studies conducted recently to evaluate the
association between HPV infections and the risk of prostate cancer, the results
remain inconclusive. Furthermore, the prevalence and distribution of overall and
individual HPV types worldwide in prostate cancer has not been reported until
now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling
data of 46 studies with 4919 prostate cancer cases, taking into account the
heterogeneity of major related parameters, including study region, specimen type,
HPV DNA source, detection method, publication calendar period and Gleason score.
Moreover, we tested the association of HPV infections with prostate cancer risks
by a meta-analysis of 26 tissue-based case-control studies. We found that the
prevalence of HPV infection was 18.93% (95% CI = 17.84-20.05%) in prostate cancer
cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52
18.99%). The prevalence varied by region, PCR primers used, publication calendar
period and Gleason score. Our study also showed a significantly increased risk of
prostate cancer with the positivity of overall HPV detected in prostate tissues
(OR = 1.79, 95% CI = 1.29-2.49) and revealed the geographic variation of
association strength (P < 0.001). In conclusion, HPV infections may contribute to
the risk of prostate cancer.
PMID- 26441166
TI - Landscape With Poplars: Paul Gauguin.
PMID- 26441167
TI - Exploring the Promise of Mindfulness as Medicine.
PMID- 26441175
TI - Facilitating Quality Improvement: Pushing the Pendulum Back Toward Process
Measures.
PMID- 26441162
TI - Detection of early stage changes associated with adipogenesis using Raman
spectroscopy under aseptic conditions.
AB - There is growing interest in the development of methods capable of non-invasive
characterization of stem cells prior to their use in cell-based therapies. Raman
spectroscopy has previously been used to detect biochemical changes commensurate
with the osteogenic, cardiogenic, and neurogenic differentiation of stem cells.
The aim of this study was to characterize the adipogenic differentiation of live
adipose derived stem cells (ASCs) under aseptic conditions. ASCs were cultured in
adipogenic or basal culture medium for 14 days in customized culture flasks
containing quartz windows. Raman spectra were acquired every 3 days. Principal
component analysis (PCA) was used to identify spectral changes in the cultures
over time. Adipogenic differentiation was confirmed using quantitative reverse
transcription polymerase chain reaction for the marker genes PPARgamma and ADIPOQ
and Oil red O staining performed. PCA demonstrated that lipid associated spectral
features varied throughout ASC differentiation with the earliest detection of the
lipid associated peak at 1,438 cm(-1) after 3 days of induction. After 7 days of
culture there were clear differences between the spectra acquired from ASCs in
adipogenic or basal culture medium. No changes were observed in the spectra
acquired from undifferentiated ASCs. Significant up-regulation in the expression
of both PPARgamma and ADIPOQ genes (P < 0.001) was observed after 14 days of
differentiation as was prominent Oil red O staining. However, the Raman sampling
process resulted in weaker gene expression compared with ASCs that had not
undergone Raman analysis. This study demonstrated that Raman spectroscopy can be
used to detect biochemical changes associated with adipogenic differentiation in
a non-invasive and aseptic manner and that this can be achieved as early as three
days into the differentiation process.
PMID- 26441176
TI - Hospital Networks and Value-Based Payment: Fertile Ground for Regionalizing High
Risk Surgery.
PMID- 26441177
TI - A PIECE OF MY MIND. All for One.
PMID- 26441178
TI - Minimally Invasive Approaches to Rectal Cancer and Diverticulitis: Does Less Mean
More?
PMID- 26441179
TI - Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III
Rectal Cancer on Pathologic Outcomes: The ACOSOG Z6051 Randomized Clinical Trial.
AB - IMPORTANCE: Evidence about the efficacy of laparoscopic resection of rectal
cancer is incomplete, particularly for patients with more advanced-stage disease.
OBJECTIVE: To determine whether laparoscopic resection is noninferior to open
resection, as determined by gross pathologic and histologic evaluation of the
resected proctectomy specimen. DESIGN, SETTING, AND PARTICIPANTS: A multicenter,
balanced, noninferiority, randomized trial enrolled patients between October 2008
and September 2013. The trial was conducted by credentialed surgeons from 35
institutions in the United States and Canada. A total of 486 patients with
clinical stage II or III rectal cancer within 12 cm of the anal verge were
randomized after completion of neoadjuvant therapy to laparoscopic or open
resection. INTERVENTIONS: Standard laparoscopic and open approaches were
performed by the credentialed surgeons. MAIN OUTCOMES AND MEASURES: The primary
outcome assessing efficacy was a composite of circumferential radial margin
greater than 1 mm, distal margin without tumor, and completeness of total
mesorectal excision. A 6% noninferiority margin was chosen according to clinical
relevance estimation. RESULTS: Two hundred forty patients with laparoscopic
resection and 222 with open resection were evaluable for analysis of the 486
enrolled. Successful resection occurred in 81.7% of laparoscopic resection cases
(95% CI, 76.8%-86.6%) and 86.9% of open resection cases (95% CI, 82.5%-91.4%) and
did not support noninferiority (difference, -5.3%; 1-sided 95% CI, -10.8% to
infinity; P for noninferiority = .41). Patients underwent low anterior resection
(76.7%) or abdominoperineal resection (23.3%). Conversion to open resection
occurred in 11.3% of patients. Operative time was significantly longer for
laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5
minutes; 95% CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean
difference, 0.3 days; 95% CI, -0.6 to 1.1), readmission within 30 days (3.3% vs
4.1%; difference, -0.7%; 95% CI, -4.2% to 2.7%), and severe complications (22.5%
vs 22.1%; difference, 0.4%; 95% CI, -4.2% to 2.7%) did not differ significantly.
Quality of the total mesorectal excision specimen in 462 operated and analyzed
surgeries was complete (77%) and nearly complete (16.5%) in 93.5% of the cases.
Negative circumferential radial margin was observed in 90% of the overall group
(87.9% laparoscopic resection and 92.3% open resection; P = .11). Distal margin
result was negative in more than 98% of patients irrespective of type of surgery
(P = .91). CONCLUSIONS AND RELEVANCE: Among patients with stage II or III rectal
cancer, the use of laparoscopic resection compared with open resection failed to
meet the criterion for noninferiority for pathologic outcomes. Pending clinical
oncologic outcomes, the findings do not support the use of laparoscopic resection
in these patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
NCT00726622.
PMID- 26441181
TI - Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis: The
SCANDIV Randomized Clinical Trial.
AB - IMPORTANCE: Perforated colonic diverticulitis usually requires surgical
resection, which is associated with significant morbidity. Cohort studies have
suggested that laparoscopic lavage may treat perforated diverticulitis with less
morbidity than resection procedures. OBJECTIVE: To compare the outcomes from
laparoscopic lavage with those for colon resection for perforated diverticulitis.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized clinical superiority
trial recruiting participants from 21 centers in Sweden and Norway from February
2010 to June 2014. The last patient follow-up was in December 2014 and final
review and verification of the medical records was assessed in March 2015.
Patients with suspected perforated diverticulitis, a clinical indication for
emergency surgery, and free air on an abdominal computed tomography scan were
eligible. Of 509 patients screened, 415 were eligible and 199 were enrolled.
INTERVENTIONS: Patients were assigned to undergo laparoscopic peritoneal lavage
(n = 101) or colon resection (n = 98) based on a computer-generated, center
stratified block randomization. All patients with fecal peritonitis (15 patients
in the laparoscopic peritoneal lavage group vs 13 in the colon resection group)
underwent colon resection. Patients with a pathology requiring treatment beyond
that necessary for perforated diverticulitis (12 in the laparoscopic lavage group
vs 13 in the colon resection group) were also excluded from the protocol
operations and treated as required for the pathology encountered. MAIN OUTCOMES
AND MEASURES: The primary outcome was severe postoperative complications (Clavien
Dindo score >IIIa) within 90 days. Secondary outcomes included other
postoperative complications, reoperations, length of operating time, length of
postoperative hospital stay, and quality of life. RESULTS: The primary outcome
was observed in 31 of 101 patients (30.7%) in the laparoscopic lavage group and
25 of 96 patients (26.0%) in the colon resection group (difference, 4.7% [95% CI,
-7.9% to 17.0%]; P = .53). Mortality at 90 days did not significantly differ
between the laparoscopic lavage group (14 patients [13.9%]) and the colon
resection group (11 patients [11.5%]; difference, 2.4% [95% CI, -7.2% to 11.9%];
P = .67). The reoperation rate was significantly higher in the laparoscopic
lavage group (15 of 74 patients [20.3%]) than in the colon resection group (4 of
70 patients [5.7%]; difference, 14.6% [95% CI, 3.5% to 25.6%]; P = .01) for
patients who did not have fecal peritonitis. The length of operating time was
significantly shorter in the laparoscopic lavage group; whereas, length of
postoperative hospital stay and quality of life did not differ significantly
between groups. Four sigmoid carcinomas were missed with laparoscopic lavage.
CONCLUSIONS AND RELEVANCE: Among patients with likely perforated diverticulitis
and undergoing emergency surgery, the use of laparoscopic lavage vs primary
resection did not reduce severe postoperative complications and led to worse
outcomes in secondary end points. These findings do not support laparoscopic
lavage for treatment of perforated diverticulitis. TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT01047462.
PMID- 26441183
TI - Challenges in Reducing Surgical "Never Events".
PMID- 26441180
TI - Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological
Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial.
AB - IMPORTANCE: Laparoscopic procedures are generally thought to have better outcomes
than open procedures. Because of anatomical constraints, laparoscopic rectal
resection may not be better because of limitations in performing an adequate
cancer resection. OBJECTIVE: To determine whether laparoscopic resection is
noninferior to open rectal cancer resection for adequacy of cancer clearance.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, noninferiority, phase 3 trial
(Australasian Laparoscopic Cancer of the Rectum; ALaCaRT) conducted between March
2010 and November 2014. Twenty-six accredited surgeons from 24 sites in Australia
and New Zealand randomized 475 patients with T1-T3 rectal adenocarcinoma less
than 15 cm from the anal verge. INTERVENTIONS: Open laparotomy and rectal
resection (n = 237) or laparoscopic rectal resection (n = 238). MAIN OUTCOMES AND
MEASURES: The primary end point was a composite of oncological factors indicating
an adequate surgical resection, with a noninferiority boundary of Delta = -8%.
Successful resection was defined as meeting all the following criteria: (1)
complete total mesorectal excision, (2) a clear circumferential margin (>=1 mm),
and (3) a clear distal resection margin (>=1 mm). Pathologists used standardized
reporting and were blinded to the method of surgery. RESULTS: A successful
resection was achieved in 194 patients (82%) in the laparoscopic surgery group
and 208 patients (89%) in the open surgery group (risk difference of -7.0% [95%
CI, -12.4% to infinity]; P = .38 for noninferiority). The circumferential
resection margin was clear in 222 patients (93%) in the laparoscopic surgery
group and in 228 patients (97%) in the open surgery group (risk difference of
3.7% [95% CI, -7.6% to 0.1%]; P = .06), the distal margin was clear in 236
patients (99%) in the laparoscopic surgery group and in 234 patients (99%) in the
open surgery group (risk difference of -0.4% [95% CI, -1.8% to 1.0%]; P = .67),
and total mesorectal excision was complete in 206 patients (87%) in the
laparoscopic surgery group and 216 patients (92%) in the open surgery group (risk
difference of -5.4% [95% CI, -10.9% to 0.2%]; P = .06). The conversion rate from
laparoscopic to open surgery was 9%. CONCLUSIONS AND RELEVANCE: Among patients
with T1-T3 rectal tumors, noninferiority of laparoscopic surgery compared with
open surgery for successful resection was not established. Although the overall
quality of surgery was high, these findings do not provide sufficient evidence
for the routine use of laparoscopic surgery. Longer follow-up of recurrence and
survival is currently being acquired. TRIAL REGISTRATION: anzctr.org Identifier:
ACTRN12609000663257.
PMID- 26441182
TI - Rehabilitation After Immobilization for Ankle Fracture: The EXACT Randomized
Clinical Trial.
AB - IMPORTANCE: The benefits of rehabilitation after immobilization for ankle
fracture are unclear. OBJECTIVES: To determine the effectiveness of a supervised
exercise program and advice (rehabilitation) compared with advice alone and to
determine if effects are moderated by fracture severity or age and sex. DESIGN,
SETTING, AND PARTICIPANTS: The EXACT trial was a pragmatic, randomized clinical
trial conducted from December 2010 to June 2014. Patients with isolated ankle
fracture presenting to fracture clinics in 7 Australian hospitals were randomized
on the day of removal of immobilization. Of 571 eligible patients, 357 chose not
to participate and 214 were allocated to rehabilitation (n = 106) or advice alone
(n = 108), with 194 (91%) followed up at 1 month, 173 (81%) at 3 months, and 170
(79%) at 6 months. There were no withdrawals attributed to adverse effects.
Recruitment terminated early on December 31, 2013 (planned enrollment, 342;
actual, 214), because funding was exhausted. INTERVENTIONS: Supervised exercise
program and advice about self-management (rehabilitation) (individually tailored,
prescribed, monitored, and progressed) or advice alone, both delivered by a
physical therapist. MAIN OUTCOMES AND MEASURES: Primary outcomes were activity
limitation assessed using the Lower Extremity Functional Scale (score range, 0
80; higher scores indicate better activity), and quality of life assessed using
the Assessment of Quality of Life (score range, 0-1; higher scores indicate
better quality of life), measured at baseline and at 1, 3 (primary time point),
and 6 months. RESULTS: Mean activity limitation and quality of life at baseline
were 30.1 (SD, 12.5) and 0.51 (SD, 0.24), respectively, for advice and 30.2 (SD,
13.2) and 0.54 (SD, 0.24) for rehabilitation, increasing to 64.3 (SD, 13.5) and
0.85 (SD, 0.17) for advice vs 64.3 (SD, 15.1) and 0.85 (SD, 0.20) for
rehabilitation at 3 months. Rehabilitation was not more effective than advice for
activity limitation (mean effect at 3 months, 0.4 [95% CI, -3.3 to 4.1]) or
quality of life (-0.01 [95% CI, -0.06 to 0.04]). Treatment effects were not
moderated by fracture severity or age and sex. CONCLUSIONS AND RELEVANCE: A
supervised exercise program and advice did not confer additional benefits in
activity limitation or quality of life compared with advice alone for patients
with isolated and uncomplicated ankle fracture. These findings do not support the
routine use of supervised exercise programs after removal of immobilization for
patients with isolated and uncomplicated ankle fracture. TRIAL REGISTRATION:
anzctr.org.au Identifier: ACTRN12610000979055.
PMID- 26441184
TI - Eliminating the Confusion Surrounding Concussions in Sports.
PMID- 26441185
TI - Recurrent Painful Abdominal Rash.
PMID- 26441186
TI - Return to Acute Care Following Ambulatory Surgery.
PMID- 26441187
TI - Extended Follow-up of a Randomized Clinical Trial of Open vs Endoscopic Release
Surgery for Carpal Tunnel Syndrome.
PMID- 26441188
TI - Treatment of Uncomplicated Acute Appendicitis.
PMID- 26441189
TI - Treatment of Uncomplicated Acute Appendicitis.
PMID- 26441190
TI - Treatment of Uncomplicated Acute Appendicitis.
PMID- 26441192
TI - Incorrect Title for Table.
PMID- 26441191
TI - Treatment of Uncomplicated Acute Appendicitis--Reply.
PMID- 26441193
TI - Omitted Financial Disclosures.
PMID- 26441194
TI - Failure to Report Financial Disclosure Information.
PMID- 26441196
TI - Laparoscopic Cholecystectomy: A Remarkable Development.
PMID- 26441198
TI - Correction with autologous fat grafting for contour changes of the breasts after
implant removal in Asian women.
AB - BACKGROUND: Patients who were diagnosed with symptomatic capsular contracture or
with safety concerns for the implant would be often reluctant to accept the
operation of implant exchange, choosing instead removal without exchange or
taking other options to rebuild their breasts. These patients may benefit from
augmenting the overlying soft tissue of the breasts with autologous fat grafting
after removing the prosthesis. OBJECTIVES: A retrospective analysis of the
patients receiving fat grafting for breast augmentation after implant removal was
performed in this study. METHODS: Between March 2011 and November 2013, 27
patients receiving autologous fat grafting after breast implant removal.
Objective evaluation was made by measuring the change in breast thickness with
ultrasonography taken before and after the treatment. Aesthetic evaluation was
performed using a 5-point Likert scale for patient satisfaction and comparing
preoperative and postoperative digital photographs for physician satisfaction.
RESULTS: The mean breast thickness change was 13.1 mm (SD = 3.3) which was an
increment by 154% in comparison to the averaged breast thickness of 8.5 mm after
implant removal. The results of patient satisfaction and physician satisfaction
were 16.3 (SD = 1.2) and 16.7 (SD = 1.6). Complications included recipient site
infection, fat necrosis, and small areas of induration. The overall complication
rate was 22.2% (6 of 27). CONCLUSION: Autologous fat grafting is beneficial for
the correction of deformed breasts after implant removal. With its preferential
fill qualities, the wide cleavage and excessive upper pole fullness associated
with existing implants can also be corrected.
PMID- 26441197
TI - JAMA PATIENT PAGE. How to Use Online Clinician Rating Systems.
PMID- 26441199
TI - Validation of a family-centred outcome questionnaire for pinnaplasty: a cross
sectional pilot study.
AB - OBJECTIVES: Comparison of pinnaplasty techniques is difficult due to variation in
the reporting of outcomes. We aimed to develop a family-centred outcome
questionnaire for use after pinnaplasty and assess it for reliability and
validity. DESIGN: Cross-sectional study. SETTING: Tertiary referral paediatric
otolaryngology centre. PARTICIPANTS: 20 prospective and 71 retrospective
pinnaplasty patients and their parent(s). METHODS: The Post-Operative Pinnaplasty
Questionnaire (POPQ) was developed after semi-structured interview with families
of children undergoing pinnaplasty. Children aged 4-16 were recruited. Three
different ear measurements (auriculocephalic angle, helix-mastoid distance and
Walker's ratio) were performed pre-operatively. Children were reviewed 3 months
post-operatively and asked to complete a POPQ and Glasgow Children's Benefit
Inventory with their parent(s). Ear measurements were repeated and data collected
on surgical technique and complications. 200 retrospective pinnaplasty patients
were posted a POPQ and Glasgow Children's Benefit Inventory and data collected on
surgical technique, complication rate and Walker's angle. MAIN OUTCOMES MEASURES:
Validity and reliability of the POPQ. RESULTS: Age range was 4-16 (median 12).
POPQ correlated well with Glasgow Children's Benefit Inventory (Spearman's rho =
0.776, P < 0.001). There was no correlation of POPQ scores with age, sex,
complication or surgical technique. POPQ score was not associated with severe
prominence pre-op nor change or degree of prominence post-op. POPQ displayed good
internal consistency (Cronbach's alpha 0.850) and ease-of-use scores.
CONCLUSIONS: We have developed a family-focused outcome tool for pinnaplasty that
displays good face validity, internal consistency and correlation with health
related quality of life and that is simple and easy to use. No correlation was
seen with more traditional measures of outcome such as complications or ear
measurements. Further refinement and testing of validity and reliability on a
larger sample is planned.
PMID- 26441200
TI - Highly Effective Conductance Modulation in Planar Silicene Field Effect Devices
Due to Buckling.
AB - Silicene is an exciting two-dimensional material that shares many of graphene's
electronic properties, but differs in its structural buckling. This buckling
allows opening a bandgap in silicene through the application of a perpendicular
electric field. Here we show that this buckling also enables highly effective
modulation of silicene's conductance by means of an in-plane electric field
applied through silicene side gates, which can be realized concurrently within
the same silicene monolayer. We illustrate this by using silicene to implement
Self-Switching Diodes (SSDs), which are two-dimensional field effect
nanorectifiers realized within a single silicene monolayer. Our quantum
simulation results show that the atomically-thin silicene SSDs, with sub-10 nm
dimensions, achieve a current rectification ratio that exceeds 200, without the
need for doping, representing a 30 fold enhancement over graphene SSDs. We
attribute this enhancement to a bandgap opening due to the in-plane electric
field, as a consequence of silicene's buckling. Our results suggest that silicene
is a promising material for the realization of planar field effect devices.
PMID- 26441201
TI - Expression of Prostaglandin-Synthesizing Enzymes (Cyclooxygenase 1,
Cyclooxygenase 2) in the Ovary of the Quail (Coturnix japonica).
AB - Cyclooxygenase is known to be the ratelimiting enzyme in the production of
prostaglandins. So far, in different bird species there have been found two
isoforms of cyclooxygenases (COX), cyclooxygenase 1 (COX-1) and cyclooxygenase 2
(COX-2). These isoforms along with prostaglandins are regarded to possess a
determining influence on the success in female reproduction. Only in a few bird
species the expression sites of cyclooxygenases have been investigated. In this
study we report on the expression of COX-1 and COX-2 in the ovary of the quail
(Coturnix japonica) using PCR, immunohistochemistry and non-radioactive in situ
hybridization techniques. Using real time-polymerase chain reaction (RT-PCR), a
distinct signal for COX-1 and COX-2 could be shown in small and large follicles
of quail ovary. Antibodies to COX-1 distinctly labelled smooth muscle cells of
the stroma, whereas COX-2 showed marked immunostaining in the thecal glands and
the ovarian surface epithelium. In the same location, a signal of the
corresponding mRNAs of COX-1 and COX-2 was found using in situ hybridization.
This expression pattern in the quail is therefore completely different from the
localization of COX-1 and COX-2 in the hen and ostrich, which suggests different
functions of the cyclooxygenases in this small galliform avian species. According
to our results, in quails COX-2 is involved in the synthesis of prostaglandins in
the ovary's interstitial glands, which until now have been considered mainly as
steroid-secreting cells. COX-1, which is expressed in the smooth muscles of the
stroma, possibly plays a role in ovulation.
PMID- 26441202
TI - Aequorin as Intracellular Ca2+ Indicator Incorporated in Follicular Lymphoma
Cells by Hypoosmotic Shock Treatment.
AB - Natural proteins can be used in measuring intracellular Ca(2+) concentration. As
one of the Ca(2+)- regulated photoproteins, aequorin has several advantages in
comparison to widely used Ca(2+) fluorescence indicators (e.g., fura-2, indo-1
and fluo-3), including high dynamic range and resistance to motion artefacts.
However, incorporation of aequorin into cells remains a challenge. Hypoosmotic
shock treatment was optimized and used as a method for loading aequorin into the
cytoplasm of follicular lymphoma cells. Measurement of aequorin luminescence in
the cells was performed using a luminometer with a sensitive photomultiplier tube
and the luminescence intensity was recalculated into intracellular [Ca(2+)]. The
value of (0.85 +/- 0.52).10-6 M was found. We show that the optimized method of
incorporation was effective for loading aequorin into follicular lymphoma cells
in vitro. The cell viability remains high immediately after the procedure. This
method can also be used for measuring intracellular Ca(2+) concentration in other
types of non-adherent cells.
PMID- 26441203
TI - Pericentric Inversion of Human Chromosome 9 Epidemiology Study in Czech Males and
Females.
AB - Pericentric inversion of human chromosome 9 [inv(9)] is a relatively common
cytogenetic finding. It is largely considered a clinically insignificant variant
of the normal human karyotype. However, numerous studies have suggested its
possible association with certain pathologies, e.g., infertility, habitual
abortions or schizophrenia. We analysed the incidence of inv(9) and the spectrum
of clinical indications for karyotyping among inv(9) carriers in three medical
genetics departments in Prague. In their cytogenetic databases, among 26,597
total records we identified 421 (1.6 %) cases of inv(9) without any concurrent
cytogenetic pathology. This study represents the world's largest epidemiological
study on inv(9) to date. The incidence of inv(9) calculated in this way from
diagnostic laboratory data does not differ from the incidence of inv(9) in three
specific populationbased samples of healthy individuals (N = 4,166) karyotyped
for preventive (amniocentesis for advanced maternal age, gamete donation) or
legal reasons (children awaiting adoption). The most frequent clinical indication
in inv(9) carriers was "idiopathic reproductive failure" - 37.1 %. The spectra
and percentages of indications in individuals with inv(9) were further
statistically evaluated for one of the departments (N = 170) by comparing
individuals with inv(9) to a control group of 661 individuals with normal
karyotypes without this inversion. The proportion of clinical referrals for
"idiopathic reproductive failure" among inv(9) cases remains higher than in
controls, but the difference is not statistically significant for both genders
combined. Analysis in separated genders showed that the incidence of "idiopathic
reproductive failure" could differ among inv(9) female and male carriers.
PMID- 26441204
TI - Benfluron Induces Cell Cycle Arrest, Apoptosis and Activation of p53 Pathway in
MOLT-4 Leukemic Cells.
AB - The aim of our study was to determine the effect of potential anti-tumour agent
benfluron on human leukemic cells MOLT-4 and elucidate the molecular mechanisms
of response of tumour cells to this chemotherapeutic agent. It has been shown
that the mechanisms of action of benfluron are complex, but the molecular
pathways of the cytostatic effect have remained unknown and the present study
contributes to their elucidation. In this work, benfluron reduced viability of
the treated cells and induced caspase-mediated apoptosis. The programmed cell
death was associated with activation of caspases 8, 9 and 3/7. Moreover, exposure
of cells to benfluron resulted in accumulation of the cells primarily in late S
and G2/M phases. The changes in the levels of key proteins show that benfluron
provoked activation of p53 and induced phosphorylation of p53 on serine 15 and
serine 392. The application of benfluron led to phosphorylation of Chk1 on serine
345 and phosphorylation of Chk2 on threonine 68 in the treated cells. Higher
doses of benfluron caused phosphorylation of ERK1/2 on threonine 202 and tyrosine
204, whereas JNK and p38 kinases were not activated. In conclusion, benfluron
induces apoptosis, cell cycle arrest in late S and G2/M phases, and activates
various signalling pathways of the DNA damage response.
PMID- 26441205
TI - Nobody Is Perfect: Comparison of the Accuracy of PCR-RFLP and KASPTM Method for
Genotyping. ADH1B and FTO Polymorphisms as Examples.
AB - DNA genotyping is among the most common analyses currently performed in
scientific research. Two high-throughput genotyping techniques are widely used -
the "classic" PCR-RFLP and probe-based methods such as TaqMan(r) PCR assay or
KASPTM genotyping. The probe-based techniques are claimed to be more accurate
than PCR-RFLP; however, the evidence for this claim is sparse. We have directly
compared results of genotyping of two SNPs (rs1229984 and rs17817449) obtained by
the PCR-RFLP and KASPTM in 1,502 adult Caucasians. The results were identical in
97.3 % and 95.9 % cases, respectively. Discrepancies (either different results or
result obtained with one but not with the other method) were addressed by
confirmatory analysis using direct sequencing. The sequencing revealed that both
methods can give incorrect results, but the frequency of incorrect genotyping of
rs1229984 and rs17817449 was very low for both methods - 0.1 % and 0.5 %,
respectively, for PCR-RFLP and 0.1 % and 0.3 %, respectively, for KASPTM. These
results confirm that the KASPTM technique is slightly more accurate, but it
achieves slightly lower call rates than PCR-RFLP. When carefully set up, both PCR
RFLP and KASPTM could have accuracy of 99.5 % or higher.
PMID- 26441206
TI - Validation of the Portuguese version of a questionnaire to measure Quality of
Care Through the Eyes of Patients with Inflammatory Bowel Disease (QUOTE-IBD).
AB - BACKGROUND/AIM: The patient's perspective on the healthcare that they receive has
become increasingly important in the assessment of healthcare quality, especially
in chronic diseases such as inflammatory bowel disease (IBD). In this context,
the questionnaire QUOTE-IBD (Quality of Care Through the Patient's Eyes with
Inflammatory Bowel Disease) was created to assess the healthcare quality from the
point of view of a patient with IBD. This questionnaire does not yet have a
validated Portuguese version (PT-QUOTE-IBD). We aimed to assess the
acceptability, validity, and reliability of PT-QUOTE-IBD. PATIENTS AND METHODS:
This was an observational longitudinal unicentric study with three sequential
phases: (a) translation and cultural adaptation of QUOTE-IBD that explores the
Importance, Performance and Quality Impact of several dimensions of healthcare;
(b) assessment of validity by correlation of the results of PT-QUOTE-IBD and
visual analogue scales (VAS); and (c) assessment of the reliability of PT-QUOTE
IBD through a second administration of the questionnaire, with a minimum interval
of 4 weeks. RESULTS: We included 114 patients with IBD (77 Crohn's disease and 37
ulcerative colitis). Fifty-nine percent of the patients completed all the
questions of QUOTE-IBD and VAS. We obtained positive and significant Pearson's
correlation coefficients between QUOTE-IBD scores and VAS for Performance and
Quality Impact of Total Care and dimensions Accessibility and Information. Thirty
four (30%) patients completed the second questionnaire adequately. We obtained
positive and significant Pearson's correlation coefficients between the two
questionnaires for Performance and Quality Impact of Total Care, Accessibility,
Continuity of Care, Courtesy and Information, and for Performance of Cost.
CONCLUSION: PT-QUOTE-IBD is acceptable, valid, and reliable in the assessment of
Performance and Quality Impact of Total Care, but not of all dimensions of
healthcare.
PMID- 26441207
TI - Prognostic significance of the EGFR pathway in nasopharyngeal carcinoma: a
systematic review and meta-analysis.
AB - OBJECTIVE: To evaluate the prognostic impact of the EGF receptor (EGFR) pathway
molecules and assess their clinical usefulness. METHODS: We conducted a
systematic review. Pubmed and EMBASE were searched January 2014. The prognostic
relevance of EGFR, JAK, PI3K, PIK3CA, STAT3, STAT5, PTEN, AKT, mTOR, GRB2, SOS,
RAF, RAS, MAPK, ERK, MEK and CCND1 in nasopharyngeal carcinoma was assessed. The
outcomes considered were overall survival, disease-free survival and tumor-node
metastasis stage. Twenty-two studies were included. Risk of bias was evaluated.
Meta-analysis for which pooled hazard ratios and 95% CIs were calculated.
CONCLUSION: EGFR overexpression predicts a worse overall survival and disease
free survival in nasopharyngeal carcinoma, but no specific causal pathway
molecule could be identified.
PMID- 26441208
TI - Unprecedented transformation of [I(-).I3(-)] to [I4(2-)] polyiodides in the solid
state: structures, phase transitions and characterization of dipyrazolium iodide
triiodide.
AB - Dipyrazolium iodide triiodide, [C3N2H5(+)]2[I(-).I3(-)], has been synthesized and
studied by means of X-ray diffraction, differential scanning calorimetry,
dielectric measurements, and UV-Vis spectroscopy. Two reversible, solid-solid
phase transitions (Imma (I) <-> (II) <->Pbam (III)) at 254 K and 182/188 K
respectively have been revealed. The anionic network experiences spectacular
changes associated with a huge rebuilding of the inorganic network from [I(-).I3(
)] to [I4(2-)]. The low frequency dielectric relaxation process occurs in phase
II with the activation energy of ca. 34 kJ mol(-1). The molecular motion of the
pyrazolium cations in [C3N2H5(+)]2[I(-).I3(-)] has been studied by means of
proton magnetic resonance studies ((1)H NMR). The ferroelastic properties of all
phases have been confirmed by polarizing microscopy observations. The molecular
mechanism of the phase transitions in the compound is proposed.
PMID- 26441209
TI - Risk Factors for Pancreatic Cancer in China: A Multicenter Case-Control Study.
AB - BACKGROUND: Despite having one of the highest mortality rates of all cancers, the
risk factors of pancreatic cancer remain unclear. We assessed risk factors of
pancreatic cancer in China. METHODS: A case-control study design was conducted
using data from four hospital-based cancer registries (Henan Provincial Cancer
Hospital, Beijing Cancer Hospital, Hebei Provincial Cancer Hospital, and Cancer
Hospital of Chinese Academy of Medical Sciences). Controls were equally matched
and selected from family members of non-pancreatic cancer patients in the same
hospitals. Face-to-face interviews were conducted by trained staff using
questionnaires. Conditional logistic regression models were used to assess odd
ratios (ORs) and 95% confident intervals (CIs). RESULTS: Among 646 recruited
participants, 323 were pancreatic cancer patients and 323 were controls.
Multivariate logistic analysis suggested that pancreatic cancer family history
(adjusted OR 1.23; 95% CI, 1.11-3.70), obesity (adjusted OR 1.77; 95% CI, 1.22
2.57), diabetes (adjusted OR 2.96; 95% CI, 1.48-5.92) and smoking (adjusted OR
1.78; 95% CI, 1.02-3.10) were risk factors for pancreatic cancer, but that
drinking tea (adjusted OR 0.49; 95% CI, 0.25-0.84) was associated with reduced
risk of pancreatic cancer. CONCLUSIONS: Cigarette smoking, family history,
obesity, and diabetes are risk factors of pancreatic cancer, which is important
information for designing early intervention and preventive strategies for
pancreatic cancer and may be beneficial to pancreatic cancer control in China.
PMID- 26441210
TI - Association of Combined Tobacco Smoking and Oral Contraceptive Use With Cervical
Intraepithelial Neoplasia 2 or 3 in Korean Women.
AB - BACKGROUND: Cigarette smoking and oral contraceptive (OC) use have been
associated with cervical neoplasia, and the combination of smoking and OC use
could influence cervical carcinogenesis. We aimed to assess the joint effect of
smoking and OC use on the risk of cervical intraepithelial neoplasia (CIN).
METHODS: From a cohort of human papillomavirus-positive subjects recruited from 6
hospitals in Korea from March 2006 to November 2012, a total of 678 subjects (411
control, 133 CIN 1, and 134 CIN 2 or 3 cases) were selected for this study (mean
age, 43 years). The risk of CIN associated with smoking and OC use on additive
and multiplicative scales was estimated via multinomial logistic regression after
adjustment for potential confounding factors. The relative excess risk due to
interaction (RERI) and the synergy index (S) were used to evaluate the additive
interaction. RESULTS: OC users (odds ratio [OR] 1.98; 95% confidence interval
[CI], 1.07-3.69) and long-term OC use (>=20 months; OR 2.71; 95% CI, 1.11-6.59)
had a higher risk of CIN 2/3, but had no association with CIN 1, compared to non
OC users. Smokers and heavy smoking (>=8 cigarettes/day) were not associated with
any CIN grade. Combined smoking and OC use (OR 4.91; 95% CI, 1.68-14.4; RERI/S,
3.77/27.4; P for multiplicative interaction = 0.003) and combined heavy smoking
and long-term OC use (OR 11.5; 95% CI, 1.88-70.4; RERI/S, 9.93/18.8; P for
multiplicative interaction = 0.009) had a higher risk of CIN 2/3 but had no
association with CIN 1 compared to combined non-smoking and non-OC use.
CONCLUSIONS: OC use and smoking acted synergistically to increase the risk of CIN
2 or 3 in Korean women.
PMID- 26441211
TI - Effects of a Public Education Campaign on the Association Between Knowledge of
Early Stroke Symptoms and Intention to Call an Ambulance at Stroke Onset: The
Acquisition of Stroke Knowledge (ASK) Study.
AB - BACKGROUND: An immediate ambulance call offers the greatest opportunity for acute
stroke therapy. Effectively using ambulance services requires strengthening the
association between knowledge of early stroke symptoms and intention to call an
ambulance at stroke onset, and encouraging the public to use ambulance services.
METHODS: The present study utilized data from the Acquisition of Stroke Knowledge
(ASK) study, which administered multiple-choice, mail-in surveys regarding
awareness of early stroke symptoms and response to a stroke attack before and
after a 2-year stroke education campaign in two areas subject to intensive and
moderate intervention, as well as in a control area, in Japan. In these three
areas, 3833 individuals (1680, 1088 and 1065 participants in intensive
intervention, moderate intervention, and control areas, respectively), aged 40 to
74 years, who responded appropriately to each survey were included in the present
study. RESULTS: After the intervention, the number of correctly identified
symptoms significantly associated with intention to call an ambulance (P < 0.05)
increased (eg, from 4 to 5 correctly identified symptoms), without increasing
choice of decoy symptoms in the intensive intervention area. Meanwhile, in other
areas, rate of identification of not only correct symptoms but also decoy
symptoms associated with intention to call an ambulance increased. Furthermore,
the association between improvement in the knowledge of stroke symptoms and
intention to call an ambulance was observed only in the intensive intervention
area (P = 0.009). CONCLUSIONS: Our results indicate that intensive interventions
are useful for strengthening the association between correct knowledge of early
stroke symptoms and intention to call an ambulance, without strengthening the
association between incorrect knowledge and intention to call an ambulance.
PMID- 26441212
TI - Increased risk of second malignant neoplasms in adolescents and young adults with
cancer.
AB - BACKGROUND: The authors describe the incidence and characteristics of secondary
malignant neoplasms (SMNs) in adolescent and young adult (AYA) cancer survivors
compared with those in younger and older cancer survivors. METHODS: Children aged
<= 14 years, AYAs aged 15 to 39, and older adults aged >= 40 years at the time of
primary diagnosis who were reported as cancer survivors in the Surveillance,
Epidemiology, and End Results (SEER) program between 1973 and 2011 were compared
in this population-based analysis. The primary analysis was the risk that an SMN
would occur >= 5 years after the original diagnosis for patients who had the more
common AYA cancers (leukemia, lymphoma, testicular malignancy, ovarian
malignancy, melanoma, and cancers of the thyroid, breast, soft tissue, or bone).
The standardized incidence ratio (SIR), absolute excess risk (AER), and
cumulative incidence of SMN for the selected cancers were assessed. The risk of
SMN for the entire cohort also was analyzed. RESULTS: Of the 148,558 AYA
survivors who were diagnosed with a selected cancer, 7384 developed an SMN 5
years after their original diagnosis. The SIRs (95% confidence intervals [CIs])
were 1.58 (95% CI, 1.55-1.62) for AYAs, 4.26 (95% CI, 3.77-4.80) for children,
and 1.10 (95% CI, 1.09-1.11) for older adults, and the AERs were 22.9, 16.6, and
14.7, respectively. The cumulative incidence of SMN at 30 years was 13.9% for the
AYA group. The most common SMNs in AYAs were breast cancer, gastrointestinal
cancer, genital cancers, and melanoma. AYAs who had received radiation therapy
had a higher cumulative incidence of SMN. CONCLUSIONS: AYAs who survive cancer
for more than 5 years have a higher relative risk of SMN compared with the
general population and have a higher absolute risk of SMN compared with younger
or older cancer survivors.
PMID- 26441213
TI - A Survey of Academic Radiology Department Chairs on Hiring Recent Graduates as
New Attending Physicians.
AB - RATIONALE AND OBJECTIVES: To determine hiring preferences among academic
radiology department chairs with emphasis on recent residency and fellowship
graduates. MATERIALS AND METHODS: With the assistance of the Society of Chairs of
Academic Radiology Departments (SCARD), an anonymous survey was distributed to
academic radiology department chairs during the time period December 2014-March
2015, with additional reminder emails during the study period. Varied multiple
choice questions were designed to gather information regarding program details;
qualities most valued in new attending hires; level of difficulty recruiting
subspecialty fellowship-trained radiologists; and the effect of the new ABR
certification process on hiring practices. Descriptive statistics and analyses
are reported. RESULTS: Surveys were completed by 79 of 184 eligible academic
radiology chairs, a response rate of 43%. The most important hiring criteria
cited were expertise in subspecialty, fellowship training, and perceived ability
to work well with referring physicians. The most popular recruitment tools cited
were hiring candidates from a chair's own program, journal ads, and academic
networks. A minority of chairs (16%), primarily those of smaller departments,
will not hire new graduates before completing board certification under the new
certification structure (P = .0143). CONCLUSIONS: Expertise in a candidate's
subspecialty was consistently cited as the most important hiring criterion.
Changes to the ABR certification process, however, will affect hiring decisions,
particularly within smaller academic departments.
PMID- 26441214
TI - Computational Insights into Excited-State Proton-Transfer Reactions in Azo and
Azomethine Dyes.
AB - State of the art density functional theory approaches are employed to provide an
accurate description of the photophysical properties of azodyes and Schiff bases
displaying intramolecular hydrogen-bonding features. These compounds exist as
tautomeric mixtures at the ground state and, in the case of Schiff bases, an
excited-state intramolecular proton transfer (ESIPT) occurs upon excitation. The
experimentally observed photophysical properties are discussed here in light of
the theoretical findings. To rationalize the different experimentally observed
radiative behavior of the azo and azomethine structures, a nonradiative decay
pathway that is possibly active in such systems is determined. The
characterization of this deactivation path, tested for two related compounds
exhibiting different fluorescence quantum yields, enables us to disentangle the
different and contrasting effects governing the excited-state behavior of these
molecular systems.
PMID- 26441215
TI - Diabetes Management in Older Adults: Seeing the Forest for the Trees.
PMID- 26441217
TI - Surgery for endometriosis-related pain.
PMID- 26441218
TI - Ab initio phonon properties of half-Heusler NiTiSn, NiZrSn and NiHfSn.
AB - A theoretical investigation of phonon properties from first-principles
calculations is carried out for the half-Heusler compounds NiXSn, [Formula: see
text], Zr and Hf. The crystal structures are optimised via ab initio calculations
within the framework of density functional theory. The phonon properties are
retrieved from harmonic and anharmonic interatomic force constants calculations
using the finite size displacements method and many-body perturbation theory. A
solution to the linearized phonon Boltzmann transport equation is then used to
compute the ab initio thermal conductivities. For X = Ti, Zr and Hf, we found
15.4, 13.3 and 15.8 W m(-1) K(-1) at 300 K, respectively. Thanks to a spectral
analysis of the velocities and lifetimes we were able appreciate the differences
in the thermal conductivities between the three compounds under study. Our
results provide insights to understand the behaviour of the thermal conductivity
and therefore to improve the thermoelectric figure of merit for such materials.
PMID- 26441220
TI - Clinical study of continuous micropump infusion of atropine and pralidoxime
chloride for treatment of severe acute organophosphorus insecticide poisoning.
AB - BACKGROUND: Our study sought to assess the effectiveness of a constant micropump
infusion of atropine and pralidoxime chloride compared with repeated-bolus doses
in patients with severe acute organophosphorus insecticide poisoning (AOPP).
METHODS: A total of 60 patients with severe AOPP, defined as cholinergic crisis
with respiratory failure or cerebral edema, were randomly divided into two groups
of 30 patients each. In the experimental group, patients received a continuous
micropump of atropine and pralidoxime chloride; in the control group, patients
were given intermittent injections of atropine and pralidoxime chloride. Primary
outcome measures were the dose of atropine required for atropinization, Acute
Physiology and Chronic Health Evaluation II (APACHE II) score at atropinization,
time to atropinization and acetylcholinesterase (AchE) recovery time.
Additionally, the case fatality rate was measured as a secondary outcome.
RESULTS: Compared to patients in the control group, the time to atropinization,
AchE recovery time, dose of atropine when atropinization occurred, and APACHE II
score in the experimental group showed a statistically significant therapeutic
effect (p < 0.05), and the case fatality rate of the experimental group was lower
than that of the control group (p < 0.05). CONCLUSION: Continuous micropump of
atropine and pralidoxime chloride combined is more effective than the use of
repeated-bolus injection in the treatment of severe acute organophosphorus
insecticide poisoning.
PMID- 26441219
TI - The hand of Homo naledi.
AB - A nearly complete right hand of an adult hominin was recovered from the Rising
Star cave system, South Africa. Based on associated hominin material, the bones
of this hand are attributed to Homo naledi. This hand reveals a long, robust
thumb and derived wrist morphology that is shared with Neandertals and modern
humans, and considered adaptive for intensified manual manipulation. However, the
finger bones are longer and more curved than in most australopiths, indicating
frequent use of the hand during life for strong grasping during locomotor
climbing and suspension. These markedly curved digits in combination with an
otherwise human-like wrist and palm indicate a significant degree of climbing,
despite the derived nature of many aspects of the hand and other regions of the
postcranial skeleton in H. naledi.
PMID- 26441216
TI - A new antibiotic regimen treats and prevents intra-amniotic
inflammation/infection in patients with preterm PROM.
AB - OBJECTIVES: To determine whether a new antibiotic regimen could reduce the
frequency of intra-amniotic inflammation/infection in patients with preterm PROM.
STUDY DESIGN: This retrospective cohort study was conducted to evaluate the
effect of antibiotics on the frequency of intra-amniotic inflammation/infection
based on the results of follow-up transabdominal amniocenteses from 89 patients
diagnosed with preterm PROM who underwent serial amniocenteses. From 1993-2003,
ampicillin and/or cephalosporins or a combination was used ("regimen 1"). A new
regimen (ceftriaxone, clarithromycin and metronidazole) was used from 2003-2012
("regimen 2"). Amniotic fluid was cultured and matrix metalloproteinase-8 (MMP-8)
concentrations were measured. RESULTS: (1) The rates of intra-amniotic
inflammation and intra-amniotic inflammation/infection in patients who received
regimen 2 decreased during treatment from 68.8% to 52.1% and from 75% to 54.2%,
respectively. In contrast, in patients who received regimen 1, the frequency of
intra-amniotic inflammation and infection/inflammation increased during treatment
(31.7% to 55% and 34.1% to 58.5%, respectively); and (2) intra-amniotic
inflammation/infection was eradicated in 33.3% of patients who received regimen
2, but in none who received regimen 1. CONCLUSION: The administration of
ceftriaxone, clarithromycin and metronidazole was associated with a more
successful eradication of intra-amniotic inflammation/infection and prevented
secondary intra-amniotic inflammation/infection more frequently than an
antibiotic regimen which included ampicillin and/or cephalosporins in patients
with preterm PROM.
PMID- 26441221
TI - Do People "Pop Out"?
AB - The human body is a highly familiar and socially very important object. Does this
mean that the human body has a special status with respect to visual attention?
In the current paper we tested whether people in natural scenes attract attention
and "pop out" or, alternatively, are at least searched for more efficiently than
targets of another category (machines). Observers in our study searched a visual
array for dynamic or static scenes containing humans amidst scenes containing
machines and vice versa. The arrays consisted of 2, 4, 6 or 8 scenes arranged in
a circular array, with targets being present or absent. Search times increased
with set size for dynamic and static human and machine targets, arguing against
pop out. However, search for human targets was more efficient than for machine
targets as indicated by shallower search slopes for human targets. Eye tracking
further revealed that observers made more first fixations to human than to
machine targets and that their on-target fixation durations were shorter for
human compared to machine targets. In summary, our results suggest that searching
for people in natural scenes is more efficient than searching for other
categories even though people do not pop out.
PMID- 26441222
TI - MicroRNA (miRNA)-Mediated Pathogenetic Signaling in Alzheimer's Disease (AD).
AB - Alzheimer's disease (AD) is an expanding health and socioeconomic concern in
industrialized societies, and the leading cause of intellectual impairment in our
aging population. The cause of AD remains unknown, and there are currently no
effective treatments to stop or reverse the progression of this uniquely human
and age-related neurological disorder. Elucidation of the AD mechanism and
factors that contribute to the initiation, progression, and spreading of this
chronic and fatal neurodegeneration will ultimately result in improved and
effective diagnostics and therapeutic strategies.microRNAs (miRNAs) comprise a
relatively recently discovered category of 20-24 nucleotide non-coding RNAs that
function post-transcriptionally in shaping the transcriptome of the cell, and in
doing so, contribute to the molecular-genetics and phenotype of human CNS health
and disease. To date about 2550 unique mature human miRNAs have been
characterized, however only highly selected miRNA populations appear to be
enriched in different anatomical compartments within the CNS.This general
commentary for the 'Special Issue: 40th Year of Neurochemical Research' will
bring into perspective (i) some very recent findings on the extraordinary
biophysics and signaling properties of CNS miRNA in AD and aging human brain;
(ii) how specific intrinsic biophysical attributes of miRNAs may play defining
roles in the establishment, proliferation and spreading of the AD phenotype; and
(iii) how miRNAs can serve as prospective therapeutic targets and biomarkers
potentially useful in the clinical management of this terminal neurological
disease whose incidence in our rapidly aging population is reaching epidemic
proportions.
PMID- 26441224
TI - Adsorbent 2D and 3D carbon matrices with protected magnetic iron nanoparticles.
AB - We report on the synthesis of two and three dimensional carbonaceous sponges
produced directly from graphene oxide (GO) into which functionalized iron
nanoparticles can be introduced to render it magnetic. This simple, low cost
procedure, wherein an iron polymeric resin precursor is introduced into the
carbon framework, results in carbon-based materials with specific surface areas
of the order of 93 and 66 m(2) g(-1), compared to approx. 4 m(2) g(-1) for
graphite, decorated with ferromagnetic iron nanoparticles giving coercivity
fields postulated to be 216 and 98 Oe, values typical for ferrite magnets, for
3.2 and 13.5 wt% Fe respectively. The strongly magnetic iron nanoparticles are
robustly anchored to the GO sheets by a layer of residual graphite, on the order
of 5 nm, formed during the pyrolysis of the precursor material. The applicability
of the carbon sponges is demonstrated in their ability to absorb, store and
subsequently elute an organic dye, Rhodamine B, from water as required. It is
possible to regenerate the carbon-iron hybrid material after adsorption by
eluting the dye with a solvent to which it has a high affinity, such as ethanol.
The use of a carbon framework opens the hybrid materials to further chemical
functionalization, for enhanced chemical uptake of contaminants, or co-decoration
with, for example, silver nanoparticles for bactericidal properties. Such
analytical properties, combined with the material's magnetic character, offer
solutions for environmental decontamination at land and sea, wastewater
purification, solvent extraction, and for the concentration of dilute species.
PMID- 26441223
TI - Rhynchophylline Protects Against the Amyloid beta-Induced Increase of Spontaneous
Discharges in the Hippocampal CA1 Region of Rats.
AB - Accumulated soluble amyloid beta (Abeta)-induced aberrant neuronal network
activity has been recognized as a key causative factor leading to cognitive
deficits which are the most outstanding characteristic of Alzheimer's disease
(AD). As an important structure associated with learning and memory, the
hippocampus is one of the brain regions that are impaired very early in AD, and
the hippocampal CA1 region is selectively vulnerable to soluble Abeta oligomers.
Our recent study showed that soluble Abeta1-42 oligomers induced hyperactivity
and perturbed the firing patterns in hippocampal neurons. Rhynchophylline (RIN)
is an important active tetracyclic oxindole alkaloid isolated from Uncaria
rhynchophylla which is a traditional Chinese medicine and often used to treat
central nervous system illnesses such as hypertension, convulsions, tremor,
stroke etc. Previous evidence showed that RIN possessed neuroprotective effects
of improving the cognitive function of mice with Alzheimer-like symptoms. In the
present study, we aimed to investigate the protective effect of RIN against
soluble Abeta1-42 oligomers-induced hippocampal hyperactivity. The results showed
that (1) the mean frequency of spontaneous discharge was increased by the local
application of 3 MUM soluble Abeta1-42 oligomers; (2) 30 MUM RIN did not exert
any obvious effects on basal physiological discharges; and (3) treatment with RIN
effectively inhibited the soluble Abeta1-42 oligomers-induced enhancement of
spontaneous discharge, in a concentration-dependent manner with an IC50 = 9.0
MUM. These in vivo electrophysiological results indicate that RIN can remold the
spontaneous discharges disturbed by Abeta and counteract the deleterious effect
of Abeta1-42 on neural circuit. The experimental findings provide further
evidence to affirm the potential of RIN as a worthy candidate for further
development into a therapeutic agent for AD.
PMID- 26441225
TI - Altering Transplantation Time to Avoid Periods of High Temperature Can
Efficiently Reduce Bacterial Wilt Disease Incidence with Tomato.
AB - Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe
problem in Southern China, where relatively high environmental temperatures
commonly prevails during the crop seasons. Previous research has indicated that
bacterial wilt disease incidence generally increases during the warm months of
summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic
fertilizers (BOFs)-organic compost fortified with pathogen-suppressive bacteria
is often lost during the periods of high environmental temperatures. Here we
studied if the disease incidence could be reduced and the BOF performance
enhanced by simply preponing and postponing the traditional seedling
transplantation times to avoid tomato plant development during periods of high
environmental temperature. To this end, a continuous, two-year field experiment
was conducted to evaluate the performance of BOF in two traditional (late-spring
[LS] and early-autumn [EA]) and two alternative (early-spring [ES] and late
autumn [LA]) crop seasons. We found that changing the transplantation times
reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES)
and 7.1% (LA), respectively. Reduction in disease incidence correlated with the
reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and
stem base. Applying BOF during alternative transplantation treatments improved
biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA).
On average, the mean maximum air temperatures were positively correlated with the
disease incidence, and negatively correlated with the BOF biocontrol efficacy
over the crop seasons. Crucially, even though preponing the transplantation time
reduced the tomato yield in general, it was still economically more profitable
compared to LS season due to reduced crop losses and relatively higher market
prices. Preponing and postponing traditional tomato transplantation times to
cooler periods could thus offer simple but effective way to control R.
solanacearum disease outbreaks.
PMID- 26441227
TI - Expression of activation markers in circulating basophils and the relationship to
allergen-induced bronchoconstriction in subjects with mild allergic asthma.
PMID- 26441226
TI - Diverse activation and differentiation of multiple B-cell subsets in patients
with atopic dermatitis but not in patients with psoriasis.
AB - BACKGROUND: Atopic dermatitis (AD) and psoriasis pathogeneses involve skin
barrier impairment and immune dysregulation; however, the contribution of B-cell
imbalances to these diseases has not yet been determined. OBJECTIVE: We sought to
quantify B-cell populations and antibody-secreting cells in the blood of patients
with AD, patients with psoriasis, and control subjects. METHODS: We studied 34
adults with moderate-to-severe AD (mean SCORAD score, 65), 24 patients with
psoriasis (mean Psoriasis Area and Severity Index score, 16), and 27 healthy
subjects using an 11-color flow cytometric antibody panel. IgD/CD27 and CD24/CD38
core gating systems were used to determine frequencies of plasmablasts and naive,
memory, transitional, and activated B cells. RESULTS: We measured increased
CD19(+)CD20(+) B-cell counts in the skin and blood of patients with AD (P < .01).
Significantly higher frequencies of chronically activated CD27(+) memory and
nonswitched memory B cells were observed in patients with AD (P < .05), with
lower values of double-negative populations (4% for patients with AD vs. 7% for
patients with psoriasis [P = .001] and 6% for control subjects [P = .02]). CD23
expression was highest in patients with AD and correlated with IgE levels (P <
.01) and disease severity (r = 0.6, P = .0002). Plasmablast frequencies and IgE
expression were highest in all memory subsets of patients with AD (P < .01).
Finally, CD19(+)CD24(++)CD38(++) transitional and CD19(+)CD24(-)CD38(-) new
memory B-cell counts were higher in patients with AD versus those in patients
with psoriasis (2.8% vs. 1.4% [P = .001] and 9.2% vs. 5.7% [P = .02],
respectively). CONCLUSIONS: AD is accompanied by systemic expansion of
transitional and chronically activated CD27(+) memory, plasmablast, and IgE
expressing memory subsets. These data create a critical basis for the future
understanding of this debilitating skin disease.
PMID- 26441229
TI - Identification of checkpoints in human T-cell development using severe combined
immunodeficiency stem cells.
AB - BACKGROUND: Severe combined immunodeficiency (SCID) represents congenital
disorders characterized by a deficiency of T cells caused by arrested development
in the thymus. Yet the nature of these developmental blocks has remained elusive
because of the difficulty of taking thymic biopsy specimens from affected
children. OBJECTIVE: We sought to identify the stages of arrest in human T-cell
development caused by various major types of SCID. METHODS: We performed
transplantation of SCID CD34(+) bone marrow stem/progenitor cells into an
optimized NSG xenograft mouse model, followed by detailed phenotypic and
molecular characterization using flow cytometry, immunoglobulin and T-cell
receptor spectratyping, and deep sequencing of immunoglobulin heavy chain (IGH)
and T-cell receptor delta (TRD) loci. RESULTS: Arrests in T-cell development
caused by mutations in IL-7 receptor alpha (IL7RA) and IL-2 receptor gamma
(IL2RG) were observed at the most immature thymocytes much earlier than expected
based on gene expression profiling of human thymocyte subsets and studies with
corresponding mouse mutants. T-cell receptor rearrangements were functionally
required at the CD4(-)CD8(-)CD7(+)CD5(+) stage given the developmental block and
extent of rearrangements in mice transplanted with Artemis-SCID cells. The
xenograft model used is not informative for adenosine deaminase-SCID, whereas
hypomorphic mutations lead to less severe arrests in development. CONCLUSION:
Transplanting CD34(+) stem cells from patients with SCID into a xenograft mouse
model provides previously unattainable insight into human T-cell development and
functionally identifies the arrest in thymic development caused by several SCID
mutations.
PMID- 26441228
TI - Association of eosinophilic esophagitis and hypertrophic cardiomyopathy.
PMID- 26441230
TI - Stress responses to repeated exposure to a combined physical and social
evaluative laboratory stressor in young healthy males.
AB - Repeated exposure to homotypic laboratory psychosocial stressors typically
instigates rapid habituation in hypothalamic-pituitary-adrenal (HPA) axis
mediated stress responses in humans. However, emerging evidence suggests the
combination of physical stress and social evaluative threat may be sufficient to
attenuate this response habituation. Neuroendocrine, cardiovascular and
subjective stress responses following repeated exposure to a combined physical
and social evaluative stress protocol were assessed to examine the habituation
response dynamic in this context. The speech task of the Trier social stress test
(TSST; Kirschbaum et al., 1993) and the socially evaluated cold pressor task
(SECPT; Schwabe et al., 2008) were administered in a combined stressor protocol.
Salivary cortisol, cardiovascular and subjective stress responses to a non-stress
control and repeat stressor exposure separated by six weeks were examined in
males (N=24) in a crossover manner. Stressor exposure resulted in significant
elevations in all stress parameters. In contrast to the commonly reported
habituation in cortisol response, a comparable post-stress response was
demonstrated. Cortisol, heart rate and subjective stress responses were also
characterised by a heightened response in anticipation to repeated stress
exposure. Blood pressure responses were comparatively uniform across repeated
exposures. Findings suggest a combined physical and social evaluative stressor is
a potentially useful method for study designs that require repeated presentation
of a homotypic stressor.
PMID- 26441231
TI - Determinants of cortisol awakening responses to naps and nighttime sleep.
AB - The cortisol awakening response (CAR) is a phenomenon describing the sharp
increase in basal cortisol levels shortly after waking from sleep. While
extensively studied, little is known about the role of sleep architecture
contributing to CAR. Furthermore, the potential for CAR after a shorter bout of
sleep--a nap--has not been directly investigated. The current studies thus aimed
at assessed sleep duration, time of day, and sleep architecture as potential
determinants of the cortisol awakening response. Saliva samples were collected
during the first hour (0, 30, 45, 60 min) following several EEG-monitored
laboratory sleep conditions. Those included afternoon naps wherein 17
participants (4 men; ages 18-26) napped for 50 min and 24 participants (11 men;
ages 18-24) napped for 90 min. Furthermore, 20 participants (10 men; ages 18-35)
visited the lab twice and in addition to staying overnight, napped 90 min in the
morning either under placebo conditions or pharmacologically-manipulated sleep
conditions (5mg Zolpidem). Cortisol increases were observed in response to each
sleep condition except to 50-min afternoon naps. Furthermore, CARs were predicted
by Stage 2 sleep when following nighttime sleep (r=.46, p=.04) and by Stage 1
sleep when following placebo morning naps (r=.54, p=.01). The current study
established cortisol awakening responses to naps and implicates sleep duration
and architecture in the generation of CAR to both napping and nighttime sleep.
Assessing CAR in conjunction with the specific type of sleep may thus contribute
to our understanding of mechanisms underlying positive and negative health
effects of napping.
PMID- 26441236
TI - Dynamics of ADAM17-Mediated Shedding of ACE2 Applied to Pancreatic Islets of Male
db/db Mice.
AB - Angiotensin-converting enzyme 2 (ACE2) gene therapy aimed at counteracting
pancreatic ACE2 depletion improves glucose regulation in two diabetic mouse
models: db/db mice and angiotensin II-infused mice. A disintegrin and
metalloproteinase 17 (ADAM17) can cause shedding of ACE2 from the cell membrane.
The aim of our studies was to determine whether ADAM17 depletes ACE2 levels in
pancreatic islets and beta-cells. Dynamics of ADAM17-mediated ACE2 shedding were
investigated in 832/13 insulinoma cells. Within a wide range of ACE2 expression
levels, including the level observed in mouse pancreatic islets, overexpression
of ADAM17 increases shed ACE2 and decreases cellular ACE2 levels. We provide a
mathematical description of shed and cellular ACE2 activities as a function of
the ADAM17 activity. The effect of ADAM17 on the cellular ACE2 content was
relatively modest with an absolute control strength value less than 0.25 and
approaching 0 at low ADAM17 activities. Although we found that ADAM17 and ACE2
are both expressed in pancreatic islets, the beta-cell is not the major cell type
expressing ACE2 in islets. During diabetes progression in 8-, 12-, and 15-week
old db/db mice, ACE2 mRNA and ACE2 activity levels in pancreatic islets were not
decreased over time nor significantly decreased compared with nondiabetic db/m
mice. Levels of ADAM17 mRNA and ADAM17 activity were also not significantly
changed. Inhibiting basal ADAM17 activity in mouse islets failed to affect ACE2
levels. We conclude that whereas ADAM17 has the ability to shed ACE2, ADAM17 does
not deplete ACE2 from pancreatic islets in diabetic db/db mice.
PMID- 26441237
TI - 17beta-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex
Difference in Acidosis-Induced Nociception.
AB - Sex differences have been reported in a number of pain conditions. Women are more
sensitive to most types of painful stimuli than men, and estrogen plays a key
role in the sex differences in pain perception. However, it is unclear whether
there is a sex difference in acidosis-evoked pain. We report here that both male
and female rats exhibit nociceptive behaviors in response to acetic acid, with
females being more sensitive than males. Local application of exogenous 17beta
estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2
and estrogen receptor (ER)-alpha agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H
pyrazole, but not ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile,
replacement also reversed attenuation of the acetic acid-induced nociceptive
response in ovariectomized females. Moreover, E2 can exert a rapid potentiating
effect on the functional activity of acid-sensing ion channels (ASICs), which
mediated the acidosis-induced events. E2 dose dependently increased the amplitude
of ASIC currents with a 42.8 +/- 1.6 nM of EC50. E2 shifted the concentration
response curve for proton upward with a 50.1% +/- 6.2% increase of the maximal
current response to proton. E2 potentiated ASIC currents via an ERalpha and
ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability
of dorsal root ganglia neurons and caused a significant increase in the amplitude
of the depolarization and the number of spikes induced by acidic stimuli. E2
potentiation of the functional activity of ASICs revealed a peripheral mechanism
underlying this sex difference in acetic acid-induced nociception.
PMID- 26441238
TI - Ghrelin Is an Essential Factor for Motilin-Induced Gastric Contraction in Suncus
murinus.
AB - Motilin was discovered in the 1970s as the most important hormone for stimulating
strong gastric contractions; however, the mechanisms by which motilin causes
gastric contraction are not clearly understood. Here, we determined the
coordinated action of motilin and ghrelin on gastric motility during fasted and
postprandial contractions by using house musk shrew (Suncus murinus; order:
Insectivora, suncus named as the laboratory strain). Motilin-induced gastric
contractions at phases I and II of the migrating motor complex were inhibited by
pretreatment with (D-Lys(3))-GHRP-6 (6 mg/kg/h), a ghrelin receptor antagonist.
Administration of the motilin receptor antagonist MA-2029 (0.1 mg/kg) and/or (D
Lys(3))-GHRP-6 (0.6 mg/kg) at the peak of phase III abolished the spontaneous
gastric phase III contractions in vivo. Motilin did not stimulate gastric
contractions in the postprandial state. However, in the presence of a low dose of
ghrelin, motilin evoked phase III-like gastric contractions even in the
postprandial state, and postprandial gastric emptying was accelerated. In
addition, pretreatment with (D-Lys(3))-GHRP-6 blocked the motilin-induced gastric
contraction in vitro and in vivo, and a gamma-aminobutyric acid (GABA) antagonist
reversed this block in gastric contraction. These results indicate that blockade
of the GABAergic pathway by ghrelin is essential for motilin-induced gastric
contraction.
PMID- 26441240
TI - Ablation of p38alpha MAPK Signaling in Osteoblast Lineage Cells Protects Mice
From Bone Loss Induced by Estrogen Deficiency.
AB - Estrogen deficiency causes bone loss by increasing the number of bone-resorbing
osteoclasts. Selective p38alpha MAPK inhibitors prevent bone-wasting effects of
estrogen withdrawal but implicated mechanisms remain to be identified. Here, we
show that inactivation of the p38alpha-encoding gene in osteoblast lineage cells
with the use of an osteocalcin-cre transgene protects mice from ovariectomy
induced bone loss (a murine model of postmenopausal osteoporosis). Ovariectomy
fails to induce bone loss, increase bone resorption, and stimulate receptor
activator of nuclear factor kappaB ligand and IL-6 expression in mice lacking
p38alpha in osteoblasts and osteocytes. Finally, TNFalpha or IL-1, which are
osteoclastogenic cytokines overproduced in the bone marrow under estrogen
deficiency, can activate p38alpha signaling in osteoblasts, but those cytokines
cannot enhance Rankl and Il6 expressions or increase osteoclast formation in p38a
deficient osteoblast cultures. These findings demonstrate that p38alpha MAPK
signaling in osteoblast lineage cells mediates ovariectomy-induced bone loss by
up-regulating receptor activator of nuclear factor kappaB ligand and IL-6
production.
PMID- 26441239
TI - A High-Calcium and Phosphate Rescue Diet and VDR-Expressing Transgenes Normalize
Serum Vitamin D Metabolite Profiles and Renal Cyp27b1 and Cyp24a1 Expression in
VDR Null Mice.
AB - Vitamin D receptor (VDR)-mediated 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)
dependent gene expression is compromised in the VDR null mouse. The biological
consequences include: hypocalcemia, hypophosphatemia, elevated parathyroid
hormone (PTH) and 1,25(OH)2D3, and consequential skeletal abnormalities. CYP24A1
is a cytochrome P450 enzyme that is involved in the side chain oxidation and
destruction of both 1,25(OH)2D3 and 25-hydroxyvitamin D3 (25-OH-D3). In the
current studies, we used liquid chromatography-tandem mass spectrometry
technology to compare the metabolic profiles of VDR null mice fed either a normal
or a calcium and phosphate-enriched rescue diet and to assess the consequence of
transgenic expression of either mouse or human VDR genes in the same background.
Serum 1,25(OH)2D3 levels in VDR null mice on normal chow were highly elevated
(>3000 pg/mL) coincident with undetectable levels of catabolites such as 24,25
(OH)2D3 and 25-OH-D3-26,23-lactone normally observed in wild-type mice. The
rescue diet corrected serum Ca(++), PTH, and 1,25(OH)2D3 values and restored
basal expression of Cyp24a1 as evidenced by both renal expression of Cyp24a1 and
detection of 24,25-(OH)2D3 and the 25-OH-D3-26,23-lactone. Unexpectedly, this
diet also resulted in supranormal levels of 3-epi-24,25-(OH)2D3 and 3-epi-25-OH
D3-26,23-lactone. The reappearance of serum 24,25-(OH)2D3 and renal Cyp24a1
expression after rescue suggests that basal levels of Cyp24a1 may be repressed by
high PTH. Introduction of transgenes for either mouse or human VDR also
normalized vitamin D metabolism in VDR null mice, whereas this metabolic pattern
was unaffected by a transgene encoding a ligand binding-deficient mutant (L233S)
human VDR. We conclude that liquid chromatography-tandem mass spectrometry-based
metabolic profiling is an ideal analytical method to study mouse models with
alterations in calcium/phosphate homeostasis.
PMID- 26441241
TI - SHBG-C57BL/ksJ-db/db: A New Mouse Model to Study SHBG Expression and Regulation
During Obesity Development.
AB - Low plasma sex hormone-binding globulin (SHBG) levels in overweight individuals
are a biomarker for the metabolic syndrome and are predictive of type 2 diabetes
and cardiovascular disease risk. There are no in vivo models to study SHBG
expression and regulation during obesity development. The main reason for this is
that the obesity-prone rodent models cannot be used to study this issue, because
rodents, unlike humans, do not express the SHBG gene in their livers. We have
developed a unique mouse model that expresses the human SHBG, and it develops
obesity, by crossing the human SHBG transgenic mice with the C57BL/ksJ-db/db
mice. The results obtained with the SHBG-C57BL/ksJ-db/db mouse model have allowed
us to determine that the SHBG overexpression in the C57BL/ksJ-db/db reduced the
body weight gain but did not change the metabolic profile of these mice.
Moreover, we elucidated the molecular mechanisms and transcription factors
causing the SHBG down-regulation during obesity development, which involved
changes in liver hepatocyte nuclear factor 4alpha and peroxisome proliferator
activated receptor-gamma mRNA and protein levels. Furthermore, these results were
confirmed using human liver biopsies. Importantly, we also showed that this model
resembles what occurs in human obese subjects, because plasma SHBG and total
testosterone levels where reduced in obese mice when compared with lean mice.
Future research using this unique mouse model will determine the role of SHBG in
the development and progression of obesity, type 2 diabetes, or fatty liver
disease.
PMID- 26441242
TI - Periodontal Bacterial DNA and Their Link to Human Cardiac Tissue: Findings of a
Pilot Study.
AB - BACKGROUND: The aim of this pilot study was to detect correlations of
microbiological DNA, inflammatory proteins, and infection parameters in patients
with periodontal disease (PD) and valvular heart disease (VHD). METHODS: A
perioperative comprehensive dental examination for the investigation of
periodontal status, including sampling of specific subgingival bacteria, was
performed in 10 patients with indication for surgery of aortic valve stenosis
with or without concomitant myocardial revascularization. Standard protocol
biopsies were taken from right atrium (A), left septal myocardium (M), and aortic
valve (V). Eleven periodontal pathogens DNA in oral and cardiac tissue samples
(A/M/V) were analyzed using polymerase chain reaction. For cardiac tissue
samples, Western blot analysis of LPS-binding protein (LBP), immunohistochemical
(IHC) detection of LBP-big42, LPS-binding protein receptor (CD14), and
macrophages (CD68), as well as inflammation scoring measurement were performed.
RESULTS: Periodontitis was present in all patients with severe intensity in 7,
moderate in 2 and mild in one patient. Same bacterial DNA was detected in A, M,
and V in different distribution, and detection was more often in atrium than in
myocardium or valve tissue. Morphological investigation revealed increased
extracellular inflammatory cell migration. In IHC markers of LBP, CD68 and CD14
showed positive findings for all patients in atrium and myocardium. CONCLUSION:
Our results demonstrate the presence of oral bacterial DNA in human cardiac
tissue, as well as inflammatory markers potentially indicating connection of PD
and VHD. Further investigation is necessary to confirm these preliminary data.
PMID- 26441243
TI - H-Ferritin Is Preferentially Incorporated by Human Erythroid Cells through
Transferrin Receptor 1 in a Threshold-Dependent Manner.
AB - Ferritin is an iron-storage protein composed of different ratios of 24 light (L)
and heavy (H) subunits. The serum level of ferritin is a clinical marker of the
body's iron level. Transferrin receptor (TFR)1 is the receptor not only for
transferrin but also for H-ferritin, but how it binds two different ligands and
the blood cell types that preferentially incorporate H-ferritin remain unknown.
To address these questions, we investigated hematopoietic cell-specific ferritin
uptake by flow cytometry. Alexa Fluor 488-labeled H-ferritin was preferentially
incorporated by erythroid cells among various hematopoietic cell lines examined,
and was almost exclusively incorporated by bone marrow erythroblasts among human
primary hematopoietic cells of various lineages. H-ferritin uptake by erythroid
cells was strongly inhibited by unlabeled H-ferritin but was only partially
inhibited by a large excess of holo-transferrin. On the other hand,
internalization of labeled holo-transferrin by these cells was not inhibited by H
ferritin. Chinese hamster ovary cells lacking functional endogenous TFR1 but
expressing human TFR1 with a mutated RGD sequence, which is required for
transferrin binding, efficiently incorporated H-ferritin, indicating that TFR1
has distinct binding sites for H-ferritin and holo-transferrin. H-ferritin uptake
by these cells required a threshold level of cell surface TFR1 expression,
whereas there was no threshold for holo-transferrin uptake. The requirement for a
threshold level of TFR1 expression can explain why among primary human
hematopoietic cells, only erythroblasts efficiently take up H-ferritin.
PMID- 26441244
TI - Hyperuricemia Inversely Correlates with Disease Severity in Taiwanese
Nonalcoholic Steatohepatitis Patients.
AB - BACKGROUND & AIMS: Asians are more susceptible to non-alcoholic steatohepatitis
(NASH) as well as metabolic disorder than other ethnicities. We aimed to assess
the interaction between metabolic factors and fibrosis in Taiwanese NASH
patients. METHODS: A total of 130 biopsy-proven Taiwanese NASH patients (94
males, age = 43.0 +/- 13.0 years) were consecutively enrolled. Their demographic,
metabolic profiles and histopathological manifestations were analyzed. RESULTS:
Twenty-four (18.5%) NASH patients were non-obese. Thirty-three (25.4%) patients
had significant fibrosis (F2) or more: 22 (16.9%) patients were of F2, whilst 11
(8.5%) patients were of advanced fibrosis (F3-4). The prevalence of metabolic
syndrome, diabetes and hypertension were 60.8%, 39.4%, and 61.5%, respectively.
There was a significant inverse correlation between hyperuricemia and fibrosis
stages, ranging from 48.4% of F0-1, 33.3% of F2, and 9.1% of F3-4, respectively
(P = 0.01, linear trend). Multivariate logistic regression analysis showed that a
decreased serum albumin level (OR = 40.0, 95% CI = 4.5-300, P = 0.001) and normal
uric acid level (OR = 5.6, 95% CI = 1.5-21.7, P = 0.01) were the significant
factors associated with significant fibrosis. CONCLUSIONS: Hyperuricemia
inversely predicts fibrosis stages. Females might carry a more disease severity
than males in Taiwanese NASH patients.
PMID- 26441245
TI - A novel approach for estimating ingested dose associated with paracetamol
overdose.
AB - AIM: In cases of paracetamol (acetaminophen, APAP) overdose, an accurate estimate
of tissue-specific paracetamol pharmacokinetics (PK) and ingested dose can offer
health care providers important information for the individualized treatment and
follow-up of affected patients. Here a novel methodology is presented to make
such estimates using a standard serum paracetamol measurement and a computational
framework. METHODS: The core component of the computational framework was a
physiologically-based pharmacokinetic (PBPK) model developed and evaluated using
an extensive set of human PK data. Bayesian inference was used for parameter and
dose estimation, allowing the incorporation of inter-study variability, and
facilitating the calculation of uncertainty in model outputs. RESULTS:
Simulations of paracetamol time course concentrations in the blood were in close
agreement with experimental data under a wide range of dosing conditions. Also,
predictions of administered dose showed good agreement with a large collection of
clinical and emergency setting PK data over a broad dose range. In addition to
dose estimation, the platform was applied for the determination of optimal blood
sampling times for dose reconstruction and quantitation of the potential role of
paracetamol conjugate measurement on dose estimation. CONCLUSIONS: Current
therapies for paracetamol overdose rely on a generic methodology involving the
use of a clinical nomogram. By using the computational framework developed in
this study, serum sample data, and the individual patient's anthropometric and
physiological information, personalized serum and liver pharmacokinetic profiles
and dose estimate could be generated to help inform an individualized overdose
treatment and follow-up plan.
PMID- 26441246
TI - Noninnocently Behaving Bridging Anions of the Widely Distributed Antioxidant
Ellagic Acid in Diruthenium Complexes.
AB - Dinuclear compounds [L2Ru(MU-E)RuL2](n) where L is acetylacetonate (acac(-), 2,4
pentanedionate), 2,2'-bipyridine (bpy), or 2-phenylazopyridine (pap) and EH4 is
ellagic acid, an antioxidative bis-catechol natural product, were studied by
voltammetric and spectroelectrochemical techniques (UV-vis-NIR and electron
paramagnetic resonance (EPR)). The electronic structures of the isolated forms
(NBu4)2[(acac)2Ru(MU-E)Ru(acac)2] ((NBu4)2[1]), [(bpy)2Ru(MU-E)Ru(bpy)2]ClO4
([2]ClO4), and [(pap)2Ru(MU-E)Ru(pap)2] ([3]) were characterized by density
functional theory (DFT) in conjunction with EPR and UV-vis-NIR measurements. The
crystal structure of (NBu4)2[1] revealed the meso form and a largely planar Ru(MU
E)Ru center. Several additional charge states of the compounds were
electrochemically accessible and were identified mostly as complexes with
noninnocently behaving pap(0/*-) or bridging ellagate (E(n-)) anions (n = 2, 3,
4) but not as mixed-valence intermediates. The free anions E(n-), n = 1-4, were
calculated by time-dependent DFT to reveal NIR transitions for the radical forms
with n = 1 and 3 and a triplet ground state for the bis(o-semiquinone) dianion
E(2-).
PMID- 26441247
TI - Viral hepatitis: A new HCV cell culture model for the next clinical challenges.
AB - Despite advances in hepatitis C treatment, substantial clinical hurdles remain to
achieve universal cure and global control of infection. Saeed et al. identified
SEC14L2 as a host factor permitting replication of clinical HCV isolates in cell
culture, providing a novel system to model infection of patient-derived viruses.
PMID- 26441248
TI - Regenerative medicine: Hepatic progenitor cells up their game in the therapeutic
stakes.
AB - Bipotential hepatic progenitor cells (HPCs) are recognized as making modest
contributions to hepatocyte regeneration, though never credited with major liver
repopulation. A new study in mice demonstrates HPCs can make a massive
contribution to hepatocyte replacement, suggesting HPCs have the potential to be
an effective cell therapy for liver failure.
PMID- 26441249
TI - Therapy: Targeting chromatin remodelling proteins to treat pancreatic cancer.
PMID- 26441250
TI - Autophagy exacerbates caspase-dependent apoptotic cell death after short times of
starvation.
AB - Autophagy is generally regarded as a mechanism to promote cell survival. However,
autophagy can occasionally be the mechanism responsible of cell demise. We have
found that a concomitant depletion of glucose, nutrients and growth factors
provoked cell death in a variety of cell lines. This death process was contingent
upon caspase activation and was mediated by BAX/BAK proteins, thus indicating its
apoptotic nature and the engagement of an intrinsic pathway. In order to abrogate
autophagy, 3-methyladenine (3-MA), BECLIN-1 siRNA and Atg5 knock-out (Tet-Off
type) approaches were alternatively employed. Irrespective of the procedure, at
short times of starvation, we found that the ongoing autophagy was sensitizing
cells to the permeabilization of the mitochondrial outer membrane (MOMP), caspase
activation and, therefore, apoptosis. On the contrary, at longer times of
starvation, autophagy displayed its characteristic pro-survival effect on cells.
As far as we know, we provide the first experimental paradigm where time is the
only variable determining the final outcome of autophagy. In other words, we have
circumscribed in time the shift transforming autophagy from a cell death to a
protection mechanism. Moreover, at short times, starvation-driven autophagy
exacerbated the apoptotic cell death caused by several antitumor agents. In
agreement with this fact, their apoptotic effects were greatly diminished by
autophagy inhibition. The implications of these facts in tumor biology will be
discussed.
PMID- 26441251
TI - Use of physiologically based kinetic (PBK) modeling to study interindividual
human variation and species differences in plasma concentrations of quercetin and
its metabolites.
AB - Biological activities of flavonoids in vivo ultimately depend on the systemic
bioavailability of the aglycones and their metabolites. We aimed to develop
physiologically based kinetic (PBK) models to predict plasma concentrations of
the flavonoid quercetin and its metabolites in individual human subjects and to
define species differences compared with male rat. The human models were
developed based on in vitro metabolic parameters derived from incubations with
pooled and 20 individual human tissue fractions and by fitting kinetic parameters
to available in vivo data. The outcomes obtained were compared to a previously
developed model for quercetin and its metabolites formation in male rat.
Quercetin-3'-O-glucuronide was predicted to be the major circulating metabolite
in 19 out of 20 individuals, while in male rat di- and tri-conjugates of
quercetin containing a glucuronic acid, sulfate and/or methyl moieties are the
major metabolites. Significant species differences occur in major circulating
metabolites of quercetin suggesting that rat is not an adequate model to study
effects of quercetin in man. The defined PBK models can be used to guide the
experimental design of in vitro experiments with flavonoids, especially to better
take into account the relevance of metabolism and the contribution of metabolites
to the biological activity in humans.
PMID- 26441252
TI - Severe arthritis predicts greater improvements in function following total knee
arthroplasty.
AB - PURPOSE: Although excellent outcomes are routinely reported following total knee
replacement, up to 20 % of patients remain dissatisfied. The aim of this study
was to determine whether pre-operative radiographic classification was associated
with functional outcomes following surgery. METHODS: A retrospective review of a
prospective arthroplasty database identified 256 patients that fulfilled the
inclusion criteria over an 18-month period. Baseline demographic data on all
patients were collected prospectively. All pre-operative radiographs were
assessed using the Kellgren and Lawrence (K&L) classification system. Patients
were prospectively assessed using the American Knee Society Score pre-operatively
and at 1, 3 and 5 years post-surgery. RESULTS: An association was found between
the pre-operative radiographic severity of arthritis and the pre-operative
American Knee Society Knee (AKSK) scores, with worsening radiographic grade
corresponding to worsening AKSK scores (p = 0.020). There was an association
between K&L classification and improvement in AKSK scores from pre-operative to 1
year (p = 0.003) and 3 years (p = 0.04), with K&L grades 3 and 4 demonstrating
the most significant improvements. On multivariate regression analysis, K&L
classification was the only significant predictor of improvement in AKSK at 1
year (p = 0.009). No correlation was found between K&L grade and the American
Knee Society Functional Scores at any stage. CONCLUSIONS: The results of this
study may help to improve satisfaction rates in total knee replacement by
targeting treatment. Patients can be counselled that although radiographic
severity of arthritic changes can predict knee-specific functional improvement,
the extent of their global functional improvement cannot. LEVEL OF EVIDENCE: IV.
PMID- 26441253
TI - The results of a consecutive series of dynamic posterior stabilizations using the
PercuDyn device.
AB - PURPOSE: To evaluate the results of a consecutive series of patients affected by
lumbar discogenic pain associated with facet pain and canal stenosis surgically
treated with the PercuDyn device. METHODS: From 2009, 129 consecutive patients
(96 M, 33 F, mean age 62) were treated with posterior dynamic stabilization
screws (PercuDyn). Inclusion criteria were minimum follow-up of 24 months; pain
localized at the lumbar spine column alone or in association to lower limb
radicular pain; magnetic resonance evidence of disc degeneration associated with
facet degeneration and canal stenosis. Patients were clinically studied using VAS
scale and Oswestry Disability Index (ODI); CT assessment of the neuroforamina and
spinal canal areas was done at 1 month of follow-up. RESULTS: At 24 months of
follow-up, 96 patients fulfilled the inclusion criteria. 96 intervertebral spaces
were treated (85 levels L5-S1, 11 levels L4-L5). The VAS scale showed a
statistically significant difference at 1 month, 6 months and 2 years with
respect to the pre-operative value (p < 0.001). The ODI score registered a
significant difference with the same fashion (p < 0.001 both at 1- and 6-month,
and 2-year follow-up with respect to the pre-operatory). At 1-month follow-up,
neuroforamina and spinal canal areas were considerably wider (p < 0.05). 70 (72.5
%) patients were satisfied of the procedure. CONCLUSIONS: In this wide cohort
study, the PercuDyn ensured good clinical and radiological results, with more
than 70 % of patients satisfied of the procedure. Very few complications were
noted, with an immediate return to daily activities. At longer follow-ups, 10 %
of patients received revision surgery.
PMID- 26441254
TI - Does surgery for Scheuermann kyphosis influence sagittal spinopelvic parameters?
AB - PURPOSE: To analyze changes in sagittal spinopelvic parameters (SSPs) after
surgical treatment of Scheuermann's Kyphosis (SK). METHODS: We analyzed 20
patients affected by SK and subjected to posterior correction of the kyphosis by
facetectomy, Ponte osteotomy, fusion and multilevel instrumentation with pedicle
screw system. Four spinal and three pelvic parameters were measured: sagittal
vertical axis (SVA), thoracic kyphosis (TK), thoracolumbar kyphosis, lumbar
lordosis (LL), pelvic incidence (PI), sacral slope (SS) and pelvic tilt (PT).
Analysis of changes in postprocedural SSPs compared to preoperative values was
performed. RESULTS: TK passed from 78.6 degrees preoperatively to 45.8 degrees
(p = 0.003). LL passed from 74.5 degrees preoperatively to 53.5 degrees (p =
0.01). No significant changes occurred in SVA, SS, PT and PI compared to
preoperative values. CONCLUSION: We confirm the positive effect of surgery by
Ponte osteotomy and posterior spinal fusion on TK and LL in patients with SK. In
our experience, pelvic parameters did not change after surgery.
PMID- 26441255
TI - Spinopelvic balance and body image perception in Parkinson's disease: analysis of
correlation.
AB - PURPOSE: The purpose of this study was to describe the association between body
image perception and sagittal balance (SB) parameters in Parkinson's Disease (PD)
patients. METHODS: 77 consecutive PD patients were included: 44 males, 33
females; 68.9 +/- 6.8 years; 5.3 +/- 3.8 years from diagnosis (YFD); Hoehn Yahr
(HY) 2.0 +/- 0.8, Unified Parkinson's Disease rating Score-Motor section (UPDRS
M) 11.8 +/- 9.3. Spinopelvic angles and SB were radiographically assessed. Body
image perception was assessed through Trunk appearance scale (TAPS) and Stunkard
Figure rating scale for BMI. Beck Depression Inventory (BDI) was used to evaluate
depressive mood. RESULTS: We detected 32 (41.5 % of cohort) Parkinson Disease
patients with scoliosis >=15 degrees Cobb. The mean calculated BMI was 27.1 +/-
3.9 kg/m(2). According to the Figure Rating Scale, the perceived BMI averaged
27.2 +/- 4.5 kg/m(2), while the mean desired BMI was 24.4 +/- 2.7 kg/m(2), TAPS
scored 3.4 +/- 0.9 points, while BDI 12.3 +/- 7.9 points. TAPS had a weak
negative correlation with the duration of disease (r = -0.25, p < 0.05) and a
correlation with H&Y score (r = 0.28, p < 0.05). Sacral Slope was weakly
correlated to the calculated BMI (r = -0.24, p < 0.05). SSA and SPA had a
negative correlation with the TAPS mean score (respectively, r = -0.36 and -0.24,
p < 0.05). BDI presented a weak correlation with TAPS (r = 0.27, p < 0.05) but
not with self esteemed BMI values (p > 0.05). CONCLUSIONS: Spinopelvic parameters
and depression had a specific and concurrent influence on trunk deformity
perception but not on BMI self-esteem.
PMID- 26441256
TI - Biomechanical and clinical study of single posterior oblique cage POLIF in the
treatment of degenerative diseases of the lumbar spine.
AB - INTRODUCTION: Aim of the study was to evaluate the biomechanical stability and
the clinical efficacy of a lumbar interbody fusion obtained by single oblique
cage implanted by a posterior approach. METHOD: Through the realization of three
finite element models (FEMs), the biomechanics of POLIF was compared to PLIF and
TLIF. Ninety-four patients underwent interbody fusion by POLIF with instrumented
posterolateral fusion. Clinical and radiographic outcomes were evaluated at
regular intervals for at least 6 months. RESULTS: The FEMs showed no
statistically significant differences in stability in compression and flexion
extension. Mean preoperative VAS score was 7.1, decreased to 2.1 at follow-up.
Mean preoperative SF-12 value was 34.5 %, increased to 75.4 % at follow-up. All
patients showed a good fusion rate and no hardware failure. DISCUSSION: POLIF
associated to instrumented posterolateral fusion is a viable and safe surgical
technique, which ensures a biomechanical stability similar to other surgical
techniques.
PMID- 26441257
TI - Long vs. short fusions for adult lumbar degenerative scoliosis: does balance
matters?
AB - PURPOSE: Surgery of adult scoliosis was based upon coronal plane radiographical
analysis using Cobb angle measurements, but recently it has been demonstrated
that sagittal spinopelvic alignment plays a critical role in determining the
final outcome. The aim of this paper is to compare the clinical and radiological
results of 81 patients affected by adult scoliosis, treated with short or long
fusions, and followed for 2-5 year follow-up. MATERIALS AND METHODS: 81 patients
affected by degenerative lumbar scoliosis managed by posterior-only surgery were
retrospectively evaluated. Fifty-seven patients underwent to a short fusion
procedure, while 24 had a long fusion. Clinical and radiographic coronal and
sagittal spinopelvic parameters were compared between the two groups. RESULTS:
Coronal Cobb angle was 24 degrees preoperatively and passed to 12 degrees in
the short fusion group, while changed from 45 degrees to 10 degrees in the long
fusion group. Lumbar lordosis was 45 degrees preoperatively and 60 degrees at
final follow-up in the short fusion group passed from 24 degrees to 55 degrees
in the long fusion group. Sacral slope passed from 25 degrees to 45 degrees in
the short fusion group, while from 10 degrees to 40 degrees in the long fusion
group. Pelvic tilt passed from 24 degrees to 13 degrees in the short fusion
group, and from 28 degrees to 23 degrees in the long fusion group. CONCLUSION:
Surgical treatment of degenerative lumbar scoliosis improved balance and
alignment of the spine, and also the coronal plane in terms of Cobb angle. These
results were associated to a consistent clinical improvement and an acceptable
rate of complications.
PMID- 26441259
TI - Surgical management of syringomyelia unrelated to Chiari malformation or spinal
cord injury.
AB - PURPOSE: Syringomyelia is a misleading disease since the problem always lies
elsewhere. Arachnoiditis, because it is radiographically difficult to discern, is
an especially insidious cause. To better guide selection from among surgical
treatment options for syringomyelia, we reviewed our case series of patients
without Chiari malformation or spinal injury. METHODS: Excluding syringomyelia
due to Chiari malformation, spinal cord injury, and tumors, 32 patients (mean age
44 years) were operated on between 1995 and 2013 and followed up for a mean of
53.8 months. Presumed causes at diagnosis, clinical and radiological findings,
type of operation, clinical and radiological outcome were reviewed. RESULTS:
Duration of clinical history varied widely (range 6-164 months). Clinical
assessment was based on the McCormick classification (15 independent, 17
dependent). Causes included birth trauma, pyogenic meningitis, tuberculous
meningitis, postoperative scarring, dysraphism, and basilar impression. Treatment
was local decompression with arachnoid lysis and shunts. Hindbrain-related
syringomyelia was differentiated from non hindbrain-related syringomyelia.
Hindbrain arachnoiditis was significantly associated with radiological findings
at the foramen magnum (p = 0.01) and craniocervical decompression (p < 0.03),
with good clinical and radiological outcome at 6 months and later follow-up
controls (p = 0.02), whereas uneven results were observed in cases of non
hindbrain arachnoiditis. CONCLUSIONS: To remove the cause of syringomyelia,
surgical planning will rely on thorough clinical history and accurate imaging to
determine the site of cerebrospinal fluid obstruction. Craniocervical
decompression to dissect basal arachnoiditis in the posterior fossa can be
recommended in hindbrain syringomyelia. Treatment of non-hindbrain arachnoiditis
is more controversial, probably owing to uncertainties about the extent of
adhesions.
PMID- 26441258
TI - Cervical spine alignment in disc arthroplasty: should we change our perspective?
AB - PURPOSE: The alignment at the cervical spine has been considered a determinant of
degeneration at the adjacent disc, but this issue in cervical disc replacement
surgery is poorly explored and discussed in this patient population. The aim of
this systematic review is to compare anterior cervical fusion and total disc
replacement (TDR) in terms of preservation of the overall cervical alignment and
complications. METHODS: A systematic review of the current literature was
performed, together with the evaluation of the methodological quality of all the
retrieved studies. RESULTS: In most of the retrieved studies, a tendency towards
a more postoperative kyphotic alignment in TDR was reported. The reported mean
complication rate was of 12.5 % (0-66.2 %). Complications associated with
cervical prosthesis included heterotopic ossification, device migration,
mechanical instability, failure, implant removal, reoperations and revision.
CONCLUSIONS: Even though cervical disc arthroplasty leads to similar outcomes
compared to arthrodesis in the middle term follow-up, no evidence of superiority
of cervical TDR is available up to date. We understand that the overall cervical
alignment after TDR tends towards the loss of lordosis, but only longer follow-up
can determine its influence on the clinical results.
PMID- 26441261
TI - D-CHART: A Novel Method of Measuring Metamorphopsia in Epiretinal Membrane and
Macular Hole.
AB - BACKGROUND: Metamorphopsia is common in macular disease. Current techniques for
measuring metamorphopsia require good vision or costly equipment. The authors
report a method that uses printed cards. METHODS: The cards have a grid of
squares arranged in a ring around fixation. There are four rings, at different
distances from fixation, divided into eight sectors. The separation of the grid
elements ranges from 0.4 degrees to 1.8 degrees . Subjects indicate in which
sector lines of squares are distorted. The sum of the maximum separation
perceived as distorted in each sector gives the total metamorphopsia score.
Thirty-three eyes with epiretinal membrane and 29 eyes with macular hole were
tested. Twenty-four eyes were tested again after surgery. In 18 subjects, the
preoperative test was performed twice to assess repeatability. RESULTS: The
median preoperative total metamorphopsia score was 10.2 for macular hole and 5.2
for epiretinal membrane. After surgery, the median total metamorphopsia score was
0.5 for macular hole and 0.45 for epiretinal membrane. Test-retest results showed
good correlation. Improvement in metamorphopsia did not correlate with change in
visual acuity. CONCLUSION: Measurement of metamorphopsia may be useful in the
management of macular hole and epiretinal membrane. D-charts are a simple and
inexpensive method of quantifying metamorphopsia that can be used in a clinical
setting.
PMID- 26441260
TI - Comprehensive Survey of Domiciliary Triatomine Species Capable of Transmitting
Chagas Disease in Southern Ecuador.
AB - BACKGROUND: Chagas disease is endemic to the southern Andean region of Ecuador,
an area with one of the highest poverty rates in the country. However, few
studies have looked into the epidemiology, vectors and transmission risks in this
region. In this study we describe the triatomine household infestation in Loja
province, determine the rate of Trypanosoma cruzi infection in triatomines and
study the risk factors associated with infestation. METHODOLOGY/PRINCIPAL
FINDINGS: An entomological survey found four triatomine species (Rhodnius
ecuadoriensis, Triatoma carrioni, Panstrongylus chinai, and P. rufotuberculatus)
infesting domiciles in 68% of the 92 rural communities examined. Nine percent of
domiciles were infested, and nymphs were observed in 80% of the infested
domiciles. Triatomines were found in all ecological regions below 2,200 masl. We
found R. ecuadoriensis (275 to 1948 masl) and T. carrioni (831 to 2242 masl)
mostly in bedrooms within the domicile, and they were abundant in chicken coops
near the domicile. Established colonies of P. chinai (175 to 2003 masl) and P.
rufotuberculatus (404 to 1613 masl) also were found in the domicile. Triatomine
infestation was associated with surrogate poverty indicators, such as poor
sanitary infrastructure (lack of latrine/toilet [w = 0.95], sewage to environment
[w = 1.0]). Vegetation type was a determinant of infestation [w = 1.0] and vector
control program insecticide spraying was a protective factor [w = 1.0]. Of the
754 triatomines analyzed, 11% were infected with Trypanosoma cruzi and 2% were
infected with T. rangeli. CONCLUSIONS/SIGNIFICANCE: To date, only limited vector
control efforts have been implemented. Together with recent reports of widespread
sylvatic triatomine infestation and frequent post-intervention reinfestation,
these results show that an estimated 100,000 people living in rural areas of
southern Ecuador are at high risk for T. cruzi infection. Therefore, there is a
need for a systematic, sustained, and monitored vector control intervention that
is coupled with improvement of socio-economic conditions.
PMID- 26441262
TI - Pseudofovea on Optical Coherence Tomography: An Unusual Appearance.
PMID- 26441263
TI - Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis Syndrome.
PMID- 26441264
TI - IMPACT OF INTERNAL LIMITING MEMBRANE PEELING ON MACULAR HOLE REOPENING: A
Systematic Review and Meta-Analysis.
AB - PURPOSE: To assess the literature regarding macular hole reopening rates
stratified by whether the internal limiting membrane (ILM) was peeled during
vitrectomy surgery. METHODS: Systematic review and meta-analysis of studies
reporting on macular hole reopenings among previously surgically closed
idiopathic macular holes. A comprehensive literature search using the National
Library of Medicine PubMed interface was used to identify potentially eligible
publications in English. The minimum mean follow-up period for reports to be
included in this study was 12 months. Analysis was divided into eyes that
underwent vitrectomy with and without ILM peeling. The primary outcome parameter
was the proportion of macular hole reopenings among previously closed holes
between the two groups. Secondary outcome parameters included duration from
initial surgery to hole reopening and preoperative and postoperative best
corrected correct visual acuities among the non-ILM peeling and ILM peeling
groups. RESULTS: A total of 50 publications reporting on 5,480 eyes met inclusion
criteria and were assessed in this meta-analysis. The reopening rate without ILM
peeling was 7.12% (125 of 1,756 eyes), compared with 1.18% (44 of 3,724 eyes)
with ILM peeling (odds ratio: 0.16; 95% confidence interval: 0.11-0.22; Fisher's
exact test: P < 0.0001). There were no other identifiable associations or risk
factors for reopening. CONCLUSION: The results of this meta-analysis support the
concept that ILM peeling during macular hole surgery reduces the likelihood of
macular hole reopening.
PMID- 26441265
TI - HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR
DEGENERATION.
AB - PURPOSE: To evaluate effects of current and past sunlight exposure and iris color
on early and late age-related macular degeneration (AMD). METHODS: Of 3,701
individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179
(31.9%) late AMD, and 1,770 (47.8%) were controls. Information about current and
past sunlight exposure, former occupation type, subdivided in indoor working and
outdoor working, and iris color were obtained by standardized interviewer
assisted questionnaires. Associations between environmental factors adjusted for
age, gender, and smoking and early and late AMD were performed by multivariate
regression analysis. RESULTS: Current sunlight exposure showed no association
with early AMD or late AMD, but past sunlight exposure (>=8 hours outside daily)
was significantly associated with early AMD (odds ratio: 5.54, 95% confidence
interval 1.25-24.58, P = 0.02) and late AMD (odds ratio: 2.77, 95% confidence
interval 1.25-6.16, P = 0.01). Outside working was found to be associated with
late AMD (odds ratio: 2.57, 95% confidence interval 1.89-3.48, P = 1.58 * 10). No
association was observed between iris color and early or late AMD. CONCLUSION:
Sunlight exposure during working life is an important risk factor for AMD,
whereas sunlight exposure after retirement seems to have less influence on the
disease development. Therefore, preventive measures, for example, wearing
sunglasses to minimize sunlight exposure, should start early to prevent
development of AMD later in life.
PMID- 26441266
TI - RISK OF RETINAL VEIN OCCLUSION WITH CENTRAL SEROUS CHORIORETINOPATHY.
AB - PURPOSE: To investigate the risk of retinal vein occlusion (RVO) after central
serous chorioretinopathy (CSCR). METHODS: The study included 2882 CSCR patients
and 17,292 control patients matched by age, sex, number of visits to an
ophthalmologist, diabetes mellitus, hypertension, and hyperlipidemia from January
2001 to December 2010 from the Taiwan Longitudinal Health Insurance Database
2000. Information for each patient was collected until December 2011. Cox
proportional hazard regression analysis was used to obtain the adjusted hazard
ratio for RVO. The RVO-free survival rate was calculated using Kaplan-Meier
analysis. RESULTS: There was a significantly higher risk of RVO in CSCR patients
than in controls (incidence rate ratio = 3.07, 95% confidence interval = 1.86
5.07). After adjustment for potential confounders, the adjusted hazard ratio for
developing RVO in the CSCR patients was 3.15 times higher than that of the
controls (adjusted hazard ratio = 3.15, 95% confidence interval = 1.91-5.21).
CONCLUSION: Central serous chorioretinopathy increases the risk of RVO. For CSCR
patients, the authors recommend thorough retinal vessel evaluation, regular
follow-up, and education regarding RVO for patients with CSCR.
PMID- 26441267
TI - Correspondence.
PMID- 26441268
TI - Correspondence.
PMID- 26441269
TI - TYPE 2 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION IMAGED BY
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB - PURPOSE: Optical coherence tomography angiography is a novel and noninvasive
technique for imaging retinal microvasculature by detecting changes in
reflectivity that is related to blood flow. The purpose of this study was to
describe Type 2 neovascularization characteristics in age-related macular
degeneration using optical coherence tomography angiography. METHODS: Fourteen
eyes of 14 consecutive patients with Type 2 neovascularization were prospectively
included. All patients underwent a complete ophthalmological examination,
including color and infrared fundus photography, fluorescein and indocyanine
green angiography, spectral domain optical coherence tomography angiography, and
optical coherence tomography angiography. RESULTS: In all cases, Type 2 lesions
could be detected by optical coherence tomography angiography, presenting as a
hyperflow lesion in the outer retina, with a glomerulus (4/14) or medusa shape
(10/14), surrounded by a dark halo. The superficial layer and the deep retina
showed no abnormal flow. Surprisingly, the Type 2 lesions could also be observed
in the presumed choriocapillaris layer. These glomerulus- or medusa-shaped
lesions were connected, in 10/14 eyes, to a thicker main branch, which seemed to
continue deep into the choroidal layers. CONCLUSION: Optical coherence tomography
angiography may be a new imaging method for the diagnosis of Type 2
neovascularization in clinical routine. However, the specificity of the features
needs to be investigated in further studies.
PMID- 26441270
TI - OUTER RETINA CAPILLARY INVASION AND ELLIPSOID ZONE LOSS IN MACULAR TELANGIECTASIA
TYPE 2 IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB - PURPOSE: Macular telangiectasia Type 2 (MacTel2) is a neurodegenerative and
vascular disease limited to the macular area, resulting ultimately in Muller cell
and photoreceptor loss and intra or subretinal proliferation. Optical coherence
tomography angiography was used to correlate the proliferation of capillaries in
the outer retina with the topography of the ellipsoid zone (EZ) loss. METHODS:
Thirty eyes of 15 patients with MacTel2 were examined using optical coherence
tomography angiography. Images of the superficial and deep capillary plexus were
analyzed and compared with en-face angio-flow images of the outer retina and en
face image of the EZ. RESULTS: Twenty-one eyes were available for the study,
including 12 with invasion of the outer retina capillary on optical coherence
tomography angiography but without subretinal neovascularization. The outer
retina capillary proliferation had a radial pattern in eight cases, formed loops
in four, and was circumscribed to an area of EZ loss on en-face images. In nine
cases, there was no outer capillary proliferation including two cases with foci
of EZ loss. CONCLUSION: Optical coherence tomography angiography shows capillary
proliferation in the outer retina corresponding to areas of EZ loss, which could
be a useful marker to monitor the efficacy of possible treatments in MacTel2
disease.
PMID- 26441271
TI - Bimanual Technique for Retinal Tacking of Epiretinal Prosthesis.
PMID- 26441272
TI - Reply: To PMID 25105313.
PMID- 26441273
TI - Reply: To PMID 25322466.
PMID- 26441274
TI - Hospitalized dogs recovery from naturally occurring heatstroke; does serum heat
shock protein 72 can provide prognostic biomarker?
AB - Heatstroke is a serious illness in dogs characterized by core temperatures above
41 degrees C with central nervous system dysfunction. Experimental heatstroke
models have tried to correlate biomarker levels with the severity of the
syndrome. Serum heat shock protein (eHSP70) levels were recently evaluated as a
biomarker of heat tolerance and acclimation, their role as a marker of heatstroke
is inconclusive. Here, we monitored eHSP70 levels in correlation with systemic
biomarkers in 30 naturally occurring canine heatstroke cases. Thirty dogs
diagnosed with environmental (33%) or exertional (66%) heatstroke admitted to
hospital (0-14 h post-injury) were tested for biomarkers of organ damage and
coagulation parameters. eHSP70 levels were measured upon admission and 4, 12, and
24 h later (T1, T2, and T3, respectively). No differences were found between
exertional and environmental heatstroke cases. The eHSP profile demonstrated an
inverted bell shape, with the lowest levels at the 12 h time point. A positive
correlation between eHSP70, lactate, and aPPT was also noted at T2 in all the
dogs in the study. Twenty-four h after presentation, eHSP70 levels returned to
those measured upon admission, this change was only significant in the survivors.
The obtained results suggest that eHSP72 level profile may be predictive of
survival.
PMID- 26441275
TI - The Electronic Health Record Paradox: Observations of a GI Consultant.
PMID- 26441276
TI - GRG Profiles: David A. Lieberman.
PMID- 26441277
TI - Mean Platelet Volume in Crohn's Disease Patients Predicts Sustained Response to a
52-Week Infliximab Therapy: A Pilot Study.
AB - BACKGROUND: The loss of response to infliximab in Crohn's disease (CD) patients
is currently a major clinical problem. Recently, mean platelet volume (MPV) has
been proposed as a new biomarker of CD activity. Here, we hypothesized that MPV
may be used as cheap and efficient biomarker of subclinical inflammation during
52-week therapy in CD patients responding to infliximab induction treatment.
AIMS: The aim of study was to establish whether MPV at baseline and pre-infusion
at week 14 are good predictors of sustained response after week 14 in CD patients
undergoing 52-week infliximab therapy. METHODS: A retrospective study of 30 adult
CD patients who underwent a 52-week course of treatment with infliximab and
achieved response at week 14 to induction treatment was performed. The
association between MPV, baseline disease parameters and maintained clinical
response or remission during infliximab therapy was assessed. RESULTS: Higher MPV
at week 14 was observed in CD patients with sustained response to infliximab
after week 14 than in patients with loss of response (p = 0.0019). In patients
with loss of response to maintenance infliximab treatment, lower DeltaMPV between
baseline and week 14 was calculated (p = 0.0003). MPV > 10.3 fl at week 14
predicts sustained response with 67 % sensitivity and 80 % specificity. DeltaMPV
between baseline and week 14 >0.4 fl predicts sustained response with 87 %
sensitivity and 93 % specificity. CONCLUSION: MPV at week 14 and DeltaMPV between
baseline and week 14 are good predictors of sustained response to infliximab
maintenance treatment in CD patients.
PMID- 26441278
TI - Clinically Diagnosed Acute Diverticulitis in Outpatients: Misdiagnosis in
Patients with Irritable Bowel Syndrome.
AB - BACKGROUND: Physicians often diagnose diverticulitis and prescribe antibiotics in
outpatients with abdominal pain and tenderness without other evidence. AIM: We
investigated the misattribution of irritable bowel syndrome (IBS) symptoms to
diverticulitis in outpatients. METHODS: In patients diagnosed with diverticulitis
and dispensed antibiotics in an integrated healthcare system, we retrospectively
compared 15,846 outpatients managed without computed tomography (CT) versus 3750
emergency department/inpatients who had CT. We assessed demographics and past
history, including 17 symptom-based somatic and 11 mental disorders and three
somatic-mental comorbidity pairs (dyads) coded over 3 years and seven drug
classes dispensed over 1 year before diagnosis. RESULTS: Univariate analysis
showed small intergroup demographic differences. Outpatients had increases in
prior diverticulitis, including outpatient-managed episodes, total somatic
diagnoses (p < .0001), eight somatic and three mental disorders (p <= .015), all
three dyads (p <= .05), and dispensing of three drug classes (p <= .016). IBS had
been diagnosed in 2399 (15.1 %) outpatients versus 361 (9.6 %) emergency
department/inpatients (p < .0001), the greatest increase in any comorbidity.
Emergency department/inpatients had no somatic comorbidity more often but more
alcohol dependence, non-dependent drug abuse, and opioid dispensing (p <= .05).
Regression analysis revealed outpatient care was independently positively
associated with younger age, non-Hispanic white race/ethnicity, less Charlson
comorbidity, diverticulitis history, IBS, chest pain, dyspepsia, fibromyalgia,
low back pain, migraine, acute reaction to stress, and antispasmodic and
anxiolytic dispensing and negatively associated with non-dependent drug abuse and
opioid dispensing (p <= .0226). CONCLUSIONS: Multiple types of indirect and
concordant evidence suggest misattribution of IBS pain to diverticulitis and
unnecessary antibiotic therapy in outpatients.
PMID- 26441279
TI - Noninvasive Prediction of Erosive Esophagitis Using a Controlled Attenuation
Parameter (CAP)-Based Risk Estimation Model.
AB - BACKGROUND: Erosive esophagitis and fatty liver share obesity and visceral fat as
common critical pathogenesis. However, the relationship between the amount of
hepatic fat and the severity of erosive esophagitis was not well investigated,
and there is no risk estimation model for erosive esophagitis. AIM: To evaluate
the relationship between the amount of hepatic fat and the severity of erosive
esophagitis and then develop a risk estimation model for erosive esophagitis.
METHODS: We enrolled 1045 consecutive participants (training cohort, n = 705;
validation cohort, n = 340) who underwent esophagogastroduodenoscopy and CAP. The
relationship between severity of fatty liver and erosive esophagitis was
investigated, and independent predictors for erosive esophagitis that have been
investigated through logistic regression analyses were used as components for
establishing a risk estimation model. RESULTS: The prevalence of erosive
gastritis was 10.7 %, and the severity of erosive esophagitis was positively
correlated with the degree of hepatic fatty accumulation (P < 0.05). A CAP-based
risk estimation model for erosive esophagitis using CAP, Body mass index, and
significant alcohol Drinking as constituent variables was established and was
dubbed the CBD score (AUROC = 0.819, range 0-11). The high-risk group (CBD score
>=3) showed significantly higher risk of having erosive esophagitis than the low
risk group (CBD score <3) (24.1 vs. 2.7 %, respectively; P < 0.001). The
diagnostic accuracy of CBD score was maintained in the validation cohort (AUROC =
0.848). CONCLUSION: The severity of erosive esophagitis was positively correlated
with the degree of hepatic fatty accumulation, and the CBD score might be a
simple CAP-based risk model for predicting erosive esophagitis.
PMID- 26441280
TI - Comparison of Risk Factors Between Small Intestinal Ulcerative and Vascular
Lesions in Occult Versus Overt Obscure Gastrointestinal Bleeding.
AB - BACKGROUND AND AIMS: The detailed risk factors such as bleeding pattern,
comorbidities, and medication usage of patients with obscure gastrointestinal
bleeding (OGIB) are largely unknown. We evaluated the risk factors related to
ulcerative and vascular lesions of the small intestine diagnosed by capsule
endoscopy or balloon-assisted endoscopy in OGIB cases. METHODS: We
retrospectively evaluated 390 OGIB cases (occult, n = 101; overt, n = 289) in our
hospital between January 2005 and March 2011 using univariate and multivariate
logistic regression analyses to determine the related risk factors. RESULTS: In
occult (n = 36) and overt (n = 120) OGIB cases, some lesions were detected in the
small intestine. Ulcerative and vascular lesions were detected in both occult (n
= 25, 69.4 %; n = 8, 22.2 %, respectively) and overt (n = 57, 47.5 %; n = 39,
32.5 %, respectively) cases. For ulcerative lesions, non-steroidal anti
inflammatory drugs were identified as a risk factor in overt cases [odds ratio
(OR) 2.974, 95 % confidence interval (CI) 1.522-5.809, P = 0.001]. For vascular
lesions, lowest hemoglobin level (OR 0.634, 95 % CI 0.422-0.953, P = 0.028) and
hematologic disease (OR 8.575, 95 % CI 1.076-68.309, P = 0.042) were identified
as risk factors in occult cases, whereas hemodialysis (OR 3.71, 95 % CI 1.315
10.467, P = 0.013) was identified in overt cases. Additionally, liver cirrhosis
was noted as a risk factor in both occult (OR 7.453, 95 % CI 1.213-45.773, P =
0.013) and overt (OR 4.900, 95 % CI 2.099-11.443, P < 0.001) OGIB cases.
CONCLUSION: There are differences in risk factors related to ulcerative versus
vascular lesions in the small intestine in occult and overt OGIB cases.
Differences were seen in both medication usage and comorbidities.
PMID- 26441281
TI - The Tolerability and Efficacy of Rapid Infliximab Infusions in Patients with
Inflammatory Bowel Disease.
AB - OBJECTIVE: Few studies have assessed the loss of efficacy or patient and
caregiver satisfaction with rapid infliximab infusions. The aim of this study is
to assess the tolerability, loss of efficacy and to describe the impact on
resource utilization and patient satisfaction in rapid infliximab infusions.
METHODS: Subjects with inflammatory bowel disease receiving rapid infliximab
infusions were included in the study. Subjects received maintenance infusions
from June 2011 to June 2013. Incidence of adverse reactions and the total number
of rapid infliximab infusions were recorded. Efficacy was compared to published
studies evaluating the long-term efficacy of infliximab infusions. Patient
satisfaction was addressed through a survey following the implementation of the
rapid infusion protocol. RESULTS: Seventy-five subjects with IBD were included in
the study. Five hundred and twenty-two rapid infliximab infusions were provided
to patients. There were no acute or delayed infusion reactions. Ten subjects (13
%) required either a dose escalation or interval adjustment between infliximab
infusions. A majority of patients reported increased satisfaction with 1-h
infliximab infusions, and 97 % of surveyed patients opted to continue rapid
infusions. The rapid infliximab infusion protocol increased infusion unit
efficiency by increasing capacity by 15 %. Cost savings in the elimination of
nursing time translated to approximately $108,150 savings at our institution.
CONCLUSIONS: Rapid infliximab infusions do not appear to increase the risk of
loss of response compared to historical studies of long-term infliximab
efficiency. A rapid infliximab infusion protocol improved efficiency in our
infusion unit and increased patient and nursing satisfaction.
PMID- 26441282
TI - Hepatic Arterial Buffer Response Maintains the Homeostasis of Graft Hemodynamics
in Patient Receiving Living Donor Liver Transplantation.
AB - BACKGROUND: In living donor liver transplantation (LDLT), the hepatic
hemodynamics plays important roles in graft regeneration, and the hepatic blood
inflows are associated with graft size. However, the data of interplay between
the hepatic arterial buffer response (HABR) and graft-to-recipient weight ratio
(GRWR) in clinical LDLT are lacking. AIMS: To identify the effect of the HABR on
the hepatic hemodynamics and recovery of graft function and to evaluate the safe
lower limit of the GRWR in carefully selected recipients. METHODS: Portal venous
and hepatic arterial blood flow was measured in recipients with ultrasonography,
and the graft functional recovery, various complications, and survive states
after LDLT were compared. RESULTS: In total, 246 consecutive patients underwent
LDLT with right lobe grafts. In total, 26 had a GRWR < 0.7 % (A), 29 had a GRWR
between 0.7 and 0.8 % (B), and 181 had a GRWR > 0.8 % (C). For small-for-size
syndrome, there was no significant difference (P = 0.176). Graft survival rates
at 1, 3, and 5 year were not different (P = 0.710). The portal vein flow and
portal vein flow per 100 g graft weight peaks were significantly higher in the A.
Hepatic arterial velocity and hepatic arterial flow decreased in all the three
groups on postoperative day 1; however, the hepatic arterial flow per 100 g graft
weight was close to healthy controls. CONCLUSIONS: HABR played important roles
not only in the homeostasis of hepatic afferent blood supply but also in
maintaining enough hepatic perfusion to the graft.
PMID- 26441283
TI - Eosinophilic Esophagitis in Children and Its Relationship with Parental
Allergies: Texas Children's Hospital Experience.
AB - BACKGROUND: Eosinophilic esophagitis (EoE) is an allergen-mediated,
clinicopathological condition affecting all ages. The characteristics of children
with EoE in the southwestern USA have not been fully described. Furthermore, very
little is known about the relationship between parental allergies and risk of EoE
in their offspring in this patient population. AIMS: To characterize children
with EoE and to examine the relationship between prevalence of parental allergies
and occurrence of EoE in their offspring at a single referral pediatric center in
the southwestern USA. METHODS: Demographic and clinical information of 126
children (<=18 years of age) with EoE was abstracted in a pre-determined data
extraction form and analyzed. The allergy history was collected from biological
parents of 61 children (parent-child cluster) with EoE in a standardized
questionnaire and analyzed. RESULTS: The median age at presentation was 8 years
(interquartile range 4-13). The majority of our patients were male (71 %) and
Caucasian (59 %). Overall, 84 % of children reported allergies. Prevalence of
food allergy was significantly higher compared to environmental allergies (P =
0.001). At least 46 % of parents reported allergies. A significantly higher
proportion of fathers had developed allergies during their childhood compared to
adulthood (P = 0.03). CONCLUSIONS: The characteristics of EoE in our patients
were similar to those reported from other parts of the country. Childhood onset
of paternal allergies appears to be a risk factor for occurrence of EoE in their
offspring. Additional research to elucidate the relationship between parental
allergies and occurrence of EoE in their offspring is warranted.
PMID- 26441284
TI - Sex-Based Differences in Asthma among Preschool and School-Aged Children in
Korea.
AB - The purpose of this study was to explore risk factors related to asthma
prevalence among preschool and school-aged children using a representative
national dataset from the Korea National Health and Nutrition Examination Survey
(KNHANES) conducted from 2009-2011. We evaluated the demographic information,
health status, household environment, socioeconomic status, and parents' health
status of 3,542 children aged 4-12 years. A sex-stratified multivariate logistic
regression was used to obtain adjusted prevalence odds ratios (ORs) and 95%
confidence intervals after accounting for primary sample units, stratification,
and sample weights. The sex-specific asthma prevalence in the 4- to 12-year-old
children was 7.39% in boys and 6.27% in girls. Boys and girls with comorbid
atopic dermatitis were more likely to have asthma than those without atopic
dermatitis (boys: OR = 2.20, p = 0.0071; girls: OR = 2.33, p = 0.0031). Boys and
girls with >=1 asthmatic parent were more likely to have asthma than those
without asthmatic parents (boys: OR = 3.90, p = 0.0006; girls: OR = 3.65, p =
0.0138). As girls got older, the prevalence of asthma decreased (OR = 0.90, p =
0.0408). Girls residing in rural areas were 60% less likely to have asthma than
those residing in urban areas (p = 0.0309). Boys with >=5 family members were
more likely to have asthma than those with <=3 family members (OR = 2.45, p =
0.0323). The factors related to asthma prevalence may differ depending on sex in
preschool and school-aged children. By understanding the characteristics of sex
based differences in asthma, individualized asthma management plans may be
established clinically.
PMID- 26441285
TI - Modification of gelatin-DNA interaction for optimised DNA extraction from gelatin
and gelatin capsule.
AB - BACKGROUND: Poor quality and quantity of DNA extracted from gelatin and gelatin
capsules often causes failure in the determination of animal species using PCR.
Gelatin, which is mainly derived from porcine and bovine, has been a matter of
concern among customers in order to fulfill religious obligation and safety
precaution against several transmissible infectious diseases associated with
bovine species. Thus, optimised DNA extraction from gelatin is very important for
successful real-time PCR detection of gelatin species. In this work, the DNA
extraction method was optimised in terms of lysis incubation period and inclusion
of pre-treatment pH modification of samples. RESULTS: The yield of DNA extracted
from porcine gelatin was significantly increased when the pH of the samples was
adjusted to pH 8.5 prior to DNA precipitation with isopropanol. The optimal pH
for DNA precipitation from bovine gelatin solution was then determined at the
original pH range of solution: pH 7.6 to 8. A DNA fragment of approximately 300
base pairs was available for PCR amplification. CONCLUSION: DNA extracted from
gelatin and commercially available capsules has been successfully utilised for
species detection using real-time PCR assay. However, significant adulterations
of porcine and bovine in pure gelatin and capsules have been detected, which
require further analytical techniques for validation. (c) 2015 Society of
Chemical Industry.
PMID- 26441287
TI - Low charge overpotentials in lithium-oxygen batteries based on tetraglyme
electrolytes with a limited amount of water.
AB - High charge overpotentials are a great challenge for the realization of lithium
oxygen batteries. Here, we construct a Li-O2 battery system by introducing a
limited amount of water into tetraglyme based electrolytes and electrolytic MnO2
(EMD) and Ru supported on Super P as cathodes for Li-O2 batteries. This results
in low charge potentials of around 3.2 V, corresponding to overpotentials of 0.24
V, and outstanding rate capability and cycling performance.
PMID- 26441286
TI - Frontoparietal Structural Connectivity Mediates the Top-Down Control of Neuronal
Synchronization Associated with Selective Attention.
AB - Neuronal synchronization reflected by oscillatory brain activity has been
strongly implicated in the mechanisms supporting selective gating. We here aimed
at identifying the anatomical pathways in humans supporting the top-down control
of neuronal synchronization. We first collected diffusion imaging data using
magnetic resonance imaging to identify the medial branch of the superior
longitudinal fasciculus (SLF), a white-matter tract connecting frontal control
areas to parietal regions. We then quantified the modulations in oscillatory
activity using magnetoencephalography in the same subjects performing a spatial
attention task. We found that subjects with a stronger SLF volume in the right
compared to the left hemisphere (or vice versa) also were the subjects who had a
better ability to modulate right compared to left hemisphere alpha and gamma band
synchronization, with the latter also predicting biases in reaction time. Our
findings implicate the medial branch of the SLF in mediating top-down control of
neuronal synchronization in sensory regions that support selective attention.
PMID- 26441288
TI - [Prevalence of non-alcoholic fatty liver disease in a population with elevated
transaminases and level of accuracy of the diagnosis in Primary Care].
AB - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated
transaminases in adults. AIM: Determine the prevalence of NASH in patients with
sustained hypertransaminasemia, and Know the adequacy of the registered in
Primary Care (AP) diagnosis. MATERIAL AND METHODS: 1) Cross-sectional study with
a random sample of patients with elevated alanine aminotransferase (ALT) held
(ALT> 32 for >=6 months), ruling out other causes of liver disease, according to
clinical, laboratory and ultrasound scan criteria in AP and 2) cross-sectional
description of all cases diagnosed with NASH recorded (K76 - ICD10) with
diagnostic adequacy analysis according to standard criteria. RESULTS: 290
patients were analyzed: 76 were diagnosed as NASH (26.1%), 44 women (57.9%).
Multivariate analysis adjusted for age and sex showed no association between NASH
and male gender (OR: 0.5; CI95%: 0.3-0.9), diabetes mellitus (DM) (OR: 2.42;
CI95%: 1.2-4.9) and hypertension blood pressure (HBP) (OR: 3.07; CI 95% 1.6-5.6).
Of the 209 diagnosed with NASH record: 51 (24.4%) met the criteria for NASH. The
rest had insufficient records. HIGHLIGHTS: 53.1% lacked sustained
hypertransaminasemia; 48% of viral serology; 11% supported and 53.1% abdominal
ultrasound registration of alcohol. CONCLUSIONS: Severe NASH is frequent among
patients with sustained hypertransaminasemia. The DM and hypertension
significantly increase the risk of NASH. The diagnosis of NASH is recorded
without considering all criteria and mainly NASH made by ultrasonography. They
should unify diagnostic criteria in the register of NASH.
PMID- 26441290
TI - Upper airway resistance during growth: A longitudinal study of children from 8 to
17 years of age.
AB - OBJECTIVE: To study upper airway breathing in 115 children annually from 8 to 17
years of age with the hypothesis that upper airway respiratory needs increase
steadily during growth and show sexual dimorphism. MATERIAL AND METHODS: To
calculate nasal resistance, airflow rate (mL/s) and oronasal pressures (cmH2O)
were measured during rest breathing in a seated position using the pressure-flow
technique. RESULTS: Median values of oronasal pressure ranged at different ages
in girls from 0.88 to 1.13 and in boys from 0.92 to 1.44 cmH2O, being 0.95 and
0.93 cmH2O at the age of 17 years, respectively. The gender differences were
statistically significant in four age groups (P < .05 by the Mann-Whitney test).
Mean values of nasal resistance decreased from 8 to 17 years of age in girls from
4.0 (+/-3.27) to 2.4 (+/-2.30) and in boys from 3.3 (+/-2.48) to 1.5 (+/-0.81)
cmH2O/L/s. However, there was an increase in resistance in 11-year-old girls and
12-year-old boys and at the age of 15 in both genders (P < .05 by paired t-test).
CONCLUSIONS: Respiratory efforts stabilize oronasal pressure to maintain vital
functions at optimal level. Nasal resistance decreased with age but increased
temporarily at the prepubertal and pubertal phases, in accordance with other
growth and possibly hormonal changes. When measuring upper airway function for
clinical purposes, especially in patients with sleep apnea, asthma, allergies,
cleft palate, or maxillary expansion, the measurements need to be compared with
age- and gender-specific values obtained from healthy children.
PMID- 26441289
TI - Million Veteran Program: A mega-biobank to study genetic influences on health and
disease.
AB - OBJECTIVE: To describe the design and ongoing conduct of the Million Veteran
Program (MVP), as an observational cohort study and mega-biobank in the
Department of Veterans Affairs (VA) health care system. STUDY DESIGN AND SETTING:
Data are being collected from participants using questionnaires, the VA
electronic health record, and a blood sample for genomic and other testing.
Several ongoing projects are linked to MVP, both as peer-reviewed research
studies and as activities to help develop an infrastructure for future, broad
based research uses. RESULTS: Formal planning for MVP commenced in 2009; the
protocol was approved in 2010, and enrollment began in 2011. As of August 3,
2015, and with a steady state of ~50 recruiting sites nationwide, N = 397,104
veterans have been enrolled. Among N = 199,348 with currently available
genotyping data, most participants (as expected) are male (92.0%) between the
ages of 50 and 69 years (55.0%). On the basis of self-reported race, white
(77.2%) and African American (13.5%) populations are well represented.
CONCLUSIONS: By helping to promote the future integration of genetic testing in
health care delivery, including clinical decision making, the MVP is designed to
contribute to the development of precision medicine.
PMID- 26441292
TI - Electrochemically Exfoliated Graphene and Graphene Oxide for Energy Storage and
Electrochemistry Applications.
AB - Top-down methods are of key importance for large-scale graphene and graphene
oxide preparation. Electrochemical exfoliation of graphite has lately gained much
interest because of the simplicity of execution, the short process time, and the
good quality of graphene that can be obtained. Here, we test three different
electrolytes, that is, H2 SO4 , Na2 SO4 , and LiClO4 , with a common exfoliation
procedure to evaluate the difference in structural and chemical properties that
result for the graphene. The properties are analyzed by means of scanning
transmission electron microscopy (STEM), Raman spectroscopy, and X-ray
photoelectron spectroscopy. We then tested the graphene materials for
electrochemical applications, measuring the heterogeneous electron transfer (HET)
rates with a Fe(CN)6 (3-/4-) redox probe, and their capacitive behavior in
alkaline solutions. We correlate the electrochemical features with the presence
of structural defects and oxygen functionalities on the graphene materials. In
particular, the use of LiClO4 during the electrochemical exfoliation of graphite
allowed the formation of highly oxidized graphene with a C/O ratio close to 4.0
and represents a possible avenue for the mass production of graphene oxide as
valid alternative to the current laborious and dangerous chemical procedures,
which also have limited scalability.
PMID- 26441293
TI - Elemental Anisotropic Growth and Atomic-Scale Structure of Shape-Controlled
Octahedral Pt-Ni-Co Alloy Nanocatalysts.
AB - Multimetallic shape-controlled nanoparticles offer great opportunities to tune
the activity, selectivity, and stability of electrocatalytic surface reactions.
However, in many cases, our synthetic control over particle size, composition,
and shape is limited requiring trial and error. Deeper atomic-scale insight in
the particle formation process would enable more rational syntheses. Here we
exemplify this using a family of trimetallic PtNiCo nanooctahedra obtained via a
low-temperature, surfactant-free solvothermal synthesis. We analyze the
competition between Ni and Co precursors under coreduction "one-step" conditions
when the Ni reduction rates prevailed. To tune the Co reduction rate and final
content, we develop a "two-step" route and track the evolution of the composition
and morphology of the particles at the atomic scale. To achieve this, scanning
transmission electron microscopy and energy dispersive X-ray elemental mapping
techniques are used. We provide evidence of a heterogeneous element distribution
caused by element-specific anisotropic growth and create octahedral nanoparticles
with tailored atomic composition like Pt1.5M, PtM, and PtM1.5 (M = Ni + Co).
These trimetallic electrocatalysts have been tested toward the oxygen reduction
reaction (ORR), showing a greatly enhanced mass activity related to commercial
Pt/C and less activity loss than binary PtNi and PtCo after 4000 potential
cycles.
PMID- 26441294
TI - Self-Assembly of Perylene Imide Molecules into 1D Nanostructures: Methods,
Morphologies, and Applications.
PMID- 26441291
TI - Structure of RagB, a major immunodominant outer-membrane surface receptor antigen
of Porphyromonas gingivalis.
AB - Porphyromonas gingivalis is the main causative agent of periodontitis. It
deregulates the inflammatory and innate host immune responses through virulence
factors, which include the immunodominant outer-membrane surface receptor
antigens A (PgRagA) and B (PgRagB), co-transcribed from the rag pathogenicity
island. The former is predicted to be a Ton-dependent porin-type translocator but
the targets of this translocation and the molecular function of PgRagB are
unknown. Phenomenologically, PgRagB has been linked with epithelial cell invasion
and virulence according to murine models. It also acts as a Toll-like receptor
agonist and promotes multiple mediators of inflammation. Hence, PgRagB is a
candidate for the development of a periodontitis vaccine, which would be
facilitated by the knowledge of its atomic structure. Here, we crystallized and
solved the structure of 54-kDa PgRagB, which revealed a single domain centered on
a curved helical scaffold. It consists of four tetratrico peptide repeats (TPR1
4), each arranged as two helices connected by a linker, plus two extra downstream
capping helices. The concave surface bears four large intertwined irregular
inserts (A-D), which contribute to an overall compact moiety. Overall, PgRagB
shows substantial structural similarity with Bacteroides thetaiotaomicron SusD
and Tannerella forsythia NanU, which are, respectively, engaged in binding and
uptake of malto-oligosaccharide/starch and sialic acid. This suggests a similar
sugar-binding function for PgRagB for uptake by the cognate PgRagA translocator,
and, consistently, three potential monosaccharide-binding sites were tentatively
assigned on the molecular surface.
PMID- 26441295
TI - High-Performance Electrochemical Catalysts Based on Three-Dimensional Porous
Architecture with Conductive Interconnected Networks.
AB - The electrochemical applications of traditional carbon nanomaterials such as
carbon nanotubes (CNTs) and graphene (G) powders are significantly impeded by
their poor three-dimensional (3D) conductivity and lack of hierarchical porous
structure. Here, we have constructed a 3D highly conductive CNTs networks and
further combined it with mesoporous carbon (mC) for the creation of a core-shell
structured (CNT@mC) composite sponge that featured 3D conductivity and
hierarchical porous structure. In the composite sponge, interconnected CNTs
efficiently eliminates the contact resistance and the hierarchical pores
significantly facilitate the mass transport. The electron transfer rates,
electroactive surface area and catalytic activity of the CNT@mC composite sponge
based catalysts were tested in the direct methanol fuel cells (DMFCs) and
electrochemical sensors. In DMFCs, the Pd nanoparticles deposited CNT@mC showed
significantly improved catalytic activity and methanol oxidization current. As
for amperometric sensing of endocrine disrupting compounds (EDCs), CNT@mC-based
catalyst gave a liner range from 10 nM to 1 mM for bisphenol A (BPA) detection
and showed great promise for simultaneous detection of multiple EDCs. BPA
recovery from environmental water further indicated the potential practical
applications of the sensor for BPA detection. Finally, the electrochemical
performance of CNT@mC were also investigated in impedimetric sensors. Good
selectivity was obtained in impedimetric sensing of BPA and the detection limit
was measured to be 0.3 nM. This study highlighted the exceptional electrochemical
properties of the CNT@mC composite sponge enabled by its 3D conductivity and
hierarchical porous structure. The strategy described may further pave a way for
the creation of novel functional materials through integrating multiple superior
properties into a single nanostructure for future clean energy technologies and
environmental monitoring systems.
PMID- 26441296
TI - Factors influencing quit attempts among male daily smokers in China.
AB - BACKGROUND: China has the largest population of smokers in the world, yet the
quit rate is low. We used data from the 2010 Global Adult Tobacco Survey China to
identify factors influencing quit attempts among male Chinese daily smokers.
METHODS: The study sample included 3303 male daily smokers. To determine the
factors that were significantly associated with making a quit attempt, we
conducted logistic regression analyses. In addition, mediation analyses were
carried out to investigate how the intermediate association among demographics
(age, education, urbanicity) and smoking-related variables affected making a quit
attempt. RESULTS: An estimated 11.0% of male daily smokers tried to quit smoking
in the 12 months prior to the survey. Logistic regression analysis indicated that
younger age (15-24 years), being advised to quit by a health care provider (HCP)
in the past 12 months, lower cigarette cost per pack, monthly or less frequent
exposure to smoking at home, and awareness of the harms of tobacco use were
significantly associated with making a quit attempt. Additional mediation
analyses showed that having knowledge of the harm of tobacco, exposure to smoking
at home, and having been advised to quit by an HCP were mediators of making a
quit attempt for other independent variables. CONCLUSION: Evidence-based tobacco
control measures such as conducting educational campaigns on the harms of tobacco
use, establishing smoke-free policies at home, and integrating tobacco cessation
advice into primary health care services can increase quit attempts and reduce
smoking among male Chinese daily smokers.
PMID- 26441297
TI - Quantifying the physical activity energy expenditure of commuters using a
combination of global positioning system and combined heart rate and movement
sensors.
AB - BACKGROUND: Active commuting may help to increase adults' physical activity
levels. However, estimates of its energy cost are derived from a small number of
studies which are laboratory-based or use self-reported measures. METHODS: Adults
working in Cambridge (UK) recruited through a predominantly workplace-based
strategy wore combined heart rate and movement sensors and global positioning
system (GPS) devices for one week, and completed synchronous day-by-day travel
diaries in 2010 and 2011. Commuting journeys were delineated using GPS data, and
metabolic intensity (standard metabolic equivalents; MET) was derived and
compared between journey types using mixed-effects linear regression. RESULTS:
182 commuting journeys were included in the analysis. Median intensity was 1.28
MET for car journeys; 1.67 MET for bus journeys; 4.61 MET for walking journeys;
6.44 MET for cycling journeys; 1.78 MET for journeys made by car in combination
with walking; and 2.21 MET for journeys made by car in combination with cycling.
The value for journeys made solely by car was significantly lower than those for
all other journey types (p<0.04). On average, 20% of the duration of journeys
incorporating any active travel (equating to 8 min) was spent in moderate-to
vigorous physical activity (MVPA). CONCLUSIONS: We have demonstrated how GPS and
activity data from a free-living sample can be used simultaneously to provide
objective estimates of commuting energy expenditure. On average, incorporating
walking or cycling into longer journeys provided over half the weekly recommended
activity levels from the commute alone. This may be an efficient way of achieving
physical activity guidelines and improving population health.
PMID- 26441298
TI - Back on track-Smoking cessation and weight changes over 9 years in a community
based cohort study.
AB - OBJECTIVE: To examine the impact of smoking cessation on body weight compared
with normal long-term weight development. METHODS: Of 1970 adults (20-69 years)
in a rural town in Denmark invited to take part in the study in 1998-2000, 1374
(70%) participated. After 9 years, 1121 participated in the follow-up study.
Weight changes were compared using multivariable regression models. RESULTS: The
mean baseline weight of never-smokers was 76.4 kg (SD 16.0). The adjusted weight
of smokers and ex-smokers differed by -4.2 kg (95% CI: -5.9, -2.6), and -0.7 kg
(95% CI: -2.5, 1.1), respectively. The adjusted weight gain rate (kg/year) of
never-smokers, smokers, and ex-smokers was 0.213, 0.127, and 0.105, respectively.
The absolute post cessation weight gain (PCWG) was 5.0 kg (SD 7.0), and the
adjusted PCWG was 2.8 kg (95% CI: 1.7, 3.9) compared with never-smokers, and 3.5
kg (95% CI: 2.3, 4.8) compared with smokers. The follow-up weight did not differ
between quitters and never-smokers (0.1 kg; 95% CI: -2.4, 2.6). CONCLUSION:
Smokers weigh less than never-smokers. By quitting, they gain weight and end up
weighing the same as comparable never-smokers. Weight gain rates differ by
smoking status. Consequently, PCWG depends on the length of follow-up. Our
graphical model indicates that smoking cessation results in a return to normal
weight development.
PMID- 26441299
TI - Smoking dependence in 18 European countries: Hard to maintain the hardening
hypothesis.
AB - OBJECTIVE: When the prevalence of smoking decreases in a population, there is a
hypothesis-the so-called "hardening hypothesis"-that the remaining smokers form a
subgroup of "hardcore smokers." Our aims were to test the hardening hypothesis
and to analyze the determinants of high dependence taking into account both
individual and country-level characteristics. METHOD: Within the Pricing Policies
and Control of Tobacco in Europe (PPACTE) project, we conducted a face-to-face
survey on smoking between January and July 2010 in 18 European countries,
including 2882 male and 2254 female smokers with complete information on smoking
dependence. The Heaviness of Smoking Index (HSI) was used as a measure of tobacco
dependence. We correlated smoking prevalence and dependence using the country as
unit of analysis. Moreover, we fitted multilevel logistic regression models.
RESULTS: Country-specific prevalence of smoking was positively, although not
significantly, correlated with the proportion of highly tobacco-dependent smokers
(overall rsp=0.203, p=0.419), both in men (rsp=0.235, p=0.347) and women
(rsp=0.455, p=0.058). Using individual-level analysis, high dependence was
positively related to age, and, although not significantly, to smoking
prevalence, and inversely related to level of education. The lack of a smoking
ban at home was positively related to smoking dependence. CONCLUSIONS: Using both
ecological and individual-level analyses, the relations between smoking
prevalence and HSI were not significant, but in the opposite direction as
compared to that assumed by the "hardening hypothesis." Therefore, our data
provide empirical evidence against this theory, thus supporting the feasibility
of an endgame strategy.
PMID- 26441300
TI - Providers' knowledge, attitudes, and practices related to colorectal cancer
control in Brazil.
AB - In Brazil, colorectal cancer (CRC) is the fourth most common cause of cancer
related death among men, and the third most common among women. We aimed to
examine CRC screening-related knowledge, attitudes, and practices among
physicians and nurses working in Brazil's network of health units, and to
describe the capacity of these units for CRC screening. In 2011, 1600 health
units were randomly selected from all 26 states and the Federal District. One
coordinator and one health care provider were selected for the interview.
Response rates were 78% for coordinators, 34% for physicians, and 65% for nurses.
The Brazilian National Cancer Institute (INCA) recommendations for CRC screening
were not often used in the health units, but screening outreach and use of CRC
exams were more common in units that were using them. Physicians and nurses
differed in most characteristics, and in their knowledge, attitudes, and
practices of CRC screening. Forty-seven percent of physicians reported not
conducting CRC screening compared to 65% of nurses. Fecal occult blood test was
most often used by physicians and nurses, but fewer physicians than nurses
perceived this exam as very effective in reducing CRC mortality. Physicians'
gender, years since graduation, and geographical region of practice in Brazil
were associated to CRC screening practice. The findings may reflect the low
influence of INCA CRC screening recommendations, physicians receiving their
medical education when CRC burden in Brazil was of low concern, and the lack of
CRC screening capacity in some regions of Brazil.
PMID- 26441301
TI - Targeting sexual health services in primary care: A systematic review of the
psychosocial correlates of adverse sexual health outcomes reported in probability
surveys of women of reproductive age.
AB - BACKGROUND: Women using primary care vary in need for sexually transmitted
infections (STIs) testing and contraception. Psychosocial correlates of these
needs may be useful for targeting services. We undertook a systematic review to
identify psychosocial correlates of STI acquisition, unplanned pregnancy (UP),
abortion and risky sexual behaviours in general population samples of women of
reproductive age. METHODS: We searched bibliographic databases for probability
surveys of women aged 16-44 years in the European Union, USA, Canada, Australia,
UK or New Zealand undertaken January 1994-January 2014. RESULTS: Eleven papers
were included. Unplanned pregnancy was associated with smoking, depression, being
single and sexual debut <16 years. Abortion was associated with lack of closeness
to parents, leaving home at an early age, and relationship break-up. Multiple
partnerships were associated with intensity of marijuana and alcohol use, and
smoking. STI diagnosis was associated with relationship break-up and younger
partners. Non-use of contraception was associated with smoking, obesity,
relationship status, sedentary lifestyles, fatalistic pregnancy attitudes and
lower alcohol use. Condom non-use was higher (at first sex) with partners 5+years
older and lower (at last sex) in less stable partnerships. CONCLUSION:
Psychosocial variables, particularly relationship status and smoking, may help
identify women in primary care for STI testing and contraception advice and
supply.
PMID- 26441303
TI - Synthesis of Unsymmetrical Sulfides and Their Oxidation to Sulfones to Discover
Potent Antileishmanial Agents.
AB - Unsymmetrical sulfides were first synthesized using combinations of a 1,3
dicarbonyl, an aromatic aldehyde and a thiol in the presence of 10 mol %
ethanolic piperidine. These sulfides derivatives were subsequently converted into
corresponding sulfones via oxidation in the presence of m-chloroperoxybenzoic
acid (m-CPBA) at ice-bath to room temperature. The former reaction was achieved
at room temperature through one-pot three-component. The later was obtained in
good yields using mild reaction conditions with flexibility in choice from a
range of substrates. The antimicrobial properties of the newly synthesized
sulfone derivatives were investigated against the protozoan parasite, Leishmania
donovani, a causative agent of visceral leishmaniasis (VL). Nine sulfone
derivatives were found to be efficacious and exhibited significant antimicrobial
activity. Further, these compounds were nontoxic on murine peritoneal macrophages
thus eliminating potential cytoxicity in the host cells. These compounds may be
indicated as potential leads in the treatment of visceral leishmaniasis.
PMID- 26441302
TI - The burden of behavioral risk factors for cardiovascular disease in Europe. A
significant prevention deficit.
AB - OBJECTIVE: The study objective was to assess the burden of major cardiovascular
disease (CVD) behavioral risk factors (BRFs) (i.e., smoking, excess body weight,
physical inactivity, risky alcohol consumption) among individuals in the
community with and without CVD history. METHODS: For the current study, a subset
of the data from the Survey of Health, Ageing and Retirement in Europe (SHARE)
was analyzed, which were collected from 26,743 individuals aged 50+ years old,
during the 1st wave of SHARE in 2004/05 in eleven European countries. RESULTS:
Among those with CVD, there is a statistically significant higher percentage of
inactive individuals (81.4% vs. 69.5 among those without CVD), and of individuals
with excess body weight (64.3%) or obese (21.6%). Patients with CVD had a lower
prevalence of smoking and risky alcohol consumption in most countries, whereas
the prevalence of high body weight and physical inactivity was higher in CVD
patients compared to individuals without CVD in almost all countries. More than
half of the population has at least two BRFs, with a significantly higher
prevalence of multiple BRFs among those diagnosed with CVD. CONCLUSION: Study
findings suggest that a significant burden of behavioral risk factors for CVD
remains in the population overall but also among patients diagnosed with CVD.
Given the significant prevalence of BRFs, the prevention benefits would be
immense for all stakeholders involved and negligence would be perilous.
PMID- 26441304
TI - Are human faces unique? A metric approach to finding single individuals without
duplicates in large samples.
AB - In the forensic sciences it is inferred that human individuals are unique and
thus can be reliably identified. The concept of individual uniqueness is claimed
to be unprovable because another individual of same characteristics may exist if
population size were infinite. It is proposed to replace "unique" with "singular"
defined as a situation when only one individual in a specific population has a
particular set of characteristics. The likelihood that in a population there will
be no duplicate individual with exactly the same set of characteristics can be
calculated from datasets of relevant characteristics. To explore singularity, the
ANSUR database which contains anthropometric measurements of 3982 individuals was
used. Eight facial metric traits were used to search for duplicates. With the
addition of each trait, the chances of finding a duplicate were reduced until
singularity was achieved. Singularity was consistently achieved at a combination
of the maximum of seven traits. The larger the traits in dimension, the faster
singularity was achieved. By exploring how singularity is achieved in subsamples
of 200, 500, etc. it has been determined that about one trait needs to be added
when the size of the target population increases by 1000 individuals. With the
combination of four facial dimensions, it is possible to achieve a probability of
finding a duplicate of the order of 10(-7), while, the combination of 8 traits
reduces probability to the order of 10(-14), that is less than one in a trillion.
PMID- 26441306
TI - Secreted Ephrin Receptor A7 Promotes Somatic Cell Reprogramming by Inducing ERK
Activity Reduction.
AB - The role of secreted molecules in cellular reprogramming has been poorly
understood. Here we identify a truncated form of ephrin receptor A7 (EPHA7) as a
key regulator of reprogramming. Truncated EPHA7 is prominently upregulated and
secreted during reprogramming. EPHA7 expression is directly regulated by OCT3/4.
EphA7 knockdown results in marked reduction of reprogramming efficiency, and the
addition of truncated EPHA7 is able to restore it. ERK activity is markedly
reduced during reprogramming, and the secreted, truncated EPHA7 is responsible
for ERK activity reduction. Remarkably, treatment of EphA7-knockdown MEFs with
the ERK pathway inhibitor restores reprogramming efficiency. Analyses show that
truncated EPHA7-induced ERK activity reduction plays an important role in the
middle phase of reprogramming. Thus, our findings uncover the importance of
secreted EPHA7-induced ERK activity reduction in reprogramming.
PMID- 26441305
TI - Crestospheres: Long-Term Maintenance of Multipotent, Premigratory Neural Crest
Stem Cells.
AB - Premigratory neural crest cells comprise a transient, embryonic population that
arises within the CNS, but subsequently migrates away and differentiates into
many derivatives. Previously, premigratory neural crest could not be maintained
in a multipotent, adhesive state without spontaneous differentiation. Here, we
report conditions that enable maintenance of neuroepithelial "crestospheres" that
self-renew and retain multipotency for weeks. Moreover, under differentiation
conditions, these cells can form multiple derivatives in vitro and in vivo after
transplantation into chick embryos. Similarly, human embryonic stem cells
directed to a neural crest fate can be maintained as crestospheres and
subsequently differentiated into several derivatives. By devising conditions that
maintain the premigratory state in vitro, these results demonstrate that
neuroepithelial neural crest precursors are capable of long-term self-renewal.
This approach will help uncover mechanisms underlying their developmental
potential, differentiation and, together with the induced pluripotent stem cell
techniques, the pathology of human neurocristopathies.
PMID- 26441309
TI - Free Thiol of Transthyretin in Human Plasma Most Accessible to
Modification/Oxidation.
AB - Free-thiol(s) in proteins, especially, when located on the surface of the
molecule, are susceptible to oxidation/modification, which may cause loss of
function or an alteration in the ternary structure. This suggests that the status
of thiol group(s) of cysteine residue(s) in a protein, i.e., free-thiol versus an
oxidized/modified form, in vivo, could reflect the physiological state of the
molecule with respect to susceptibility to oxidative stress. To address this
issue, we established an efficient method for isolating proteins that contain
free thiol groups from a complex mixture, which permits the amount of free-thiol
form(s) to modified/oxidized forms to be estimated. Albumin, which accounts for
55% of the total plasma proteins and has such a free thiol and has been reported
to scavenge various reactive oxygen species (ROS) in vivo. The developed method
was used to isolate the free form of albumin from fresh plasma. However, contrary
to our expectations, transthyretin (TTR), which also has a single free thiol, was
found to be the major protein that was the most susceptible to
modification/oxidation. In addition, the free-thiol form could be separated from
oxidized or modified molecules, permitting the relative abundance of the free
thiol form to be estimated. The findings show that the levels of the free-thiol
form of TTR in plasma was significantly lowered after a hydrogen peroxide
treatment, even at low concentrations (0.1 mM), suggesting that TTR could be a
useful biomarker for monitoring a ROS imbalance in relation to various oxidative
stress conditions.
PMID- 26441307
TI - Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance
Regenerative Hematopoiesis.
AB - Hematopoietic stem cells (HSCs) inhabit distinct microenvironments within the
adult bone marrow (BM), which govern the delicate balance between HSC quiescence,
self-renewal, and differentiation. Previous reports have proposed that HSCs
localize to the vascular niche, comprised of endothelium and tightly associated
perivascular cells. Herein, we examine the capacity of BM endothelial cells
(BMECs) to support ex vivo and in vivo hematopoiesis. We demonstrate that AKT1
activated BMECs (BMEC-Akt1) have a unique transcription factor/cytokine profile
that supports functional HSCs in lieu of complex serum and cytokine
supplementation. Additionally, transplantation of BMEC-Akt1 cells enhanced
regenerative hematopoiesis following myeloablative irradiation. These data
demonstrate that BMEC-Akt1 cultures can be used as a platform for the discovery
of pro-HSC factors and justify the utility of BMECs as a cellular therapy. This
technical advance may lead to the development of therapies designed to decrease
pancytopenias associated with myeloablative regimens used to treat a wide array
of disease states.
PMID- 26441310
TI - Get Your Atoms in Order--An Open-Source Implementation of a Novel and Robust
Molecular Canonicalization Algorithm.
AB - Finding a canonical ordering of the atoms in a molecule is a prerequisite for
generating a unique representation of the molecule. The canonicalization of a
molecule is usually accomplished by applying some sort of graph relaxation
algorithm, the most common of which is the Morgan algorithm. There are known
issues with that algorithm that lead to noncanonical atom orderings as well as
problems when it is applied to large molecules like proteins. Furthermore, each
cheminformatics toolkit or software provides its own version of a canonical
ordering, most based on unpublished algorithms, which also complicates the
generation of a universal unique identifier for molecules. We present an
alternative canonicalization approach that uses a standard stable-sorting
algorithm instead of a Morgan-like index. Two new invariants that allow canonical
ordering of molecules with dependent chirality as well as those with highly
symmetrical cyclic graphs have been developed. The new approach proved to be
robust and fast when tested on the 1.45 million compounds of the ChEMBL 20 data
set in different scenarios like random renumbering of input atoms or SMILES round
tripping. Our new algorithm is able to generate a canonical order of the atoms of
protein molecules within a few milliseconds. The novel algorithm is implemented
in the open-source cheminformatics toolkit RDKit. With this paper, we provide a
reference Python implementation of the algorithm that could easily be integrated
in any cheminformatics toolkit. This provides a first step toward a common
standard for canonical atom ordering to generate a universal unique identifier
for molecules other than InChI.
PMID- 26441311
TI - Host-Parasite Interactions from the Inside: Plant Reproductive Ontogeny Drives
Specialization in Parasitic Insects.
AB - Host plant interactions are likely key drivers of evolutionary processes involved
in the diversification of phytophagous insects. Granivory has received
substantial attention for its crucial role in shaping the interaction between
plants and their seed parasites, but fine-scale mechanisms explaining the role of
host plant reproductive biology on specialization of seed parasites remain poorly
described. In a comparative approach using plant histological techniques, we
tested the hypotheses that different seed parasite species synchronize their life
cycles to specific stages in seed development, and that the stage they target
depends on major differences in seed development programs. In a pinaceous system,
seed storage products are initiated before ovule fertilization and the wasps
target the ovule's nucellus during megagametogenesis, a stage at which larvae may
benefit from the by-products derived from both secreting cells and dying nucellar
cells. In a cupressaceous system, oviposition activity peaks later, during
embryogenesis, and the wasps target the ovule's megagametophyte where larvae may
benefit from cell disintegration during embryogenesis. Our cytohistological
approach shows for the first time how, despite divergent oviposition targets,
different parasite species share a common strategy that consists of first
competing for nutrients with developing plant structures, and then consuming
these developed structures to complete their development. Our results support the
prediction that seed developmental program is an axis for specialization in seed
parasites, and that it could be an important parameter in models of their
ecological and taxonomic divergence. This study provides the basis for further
investigating the possibility of the link between plant ontogeny and pre
dispersal seed parasitism.
PMID- 26441312
TI - Work characteristics and health: how to analyze change.
PMID- 26441313
TI - Concentration of antiepileptic drugs in persons with epilepsy: a comparative
study in serum and saliva.
AB - AIM OF THE STUDY: The monitoring of antiepileptic drugs (AEDs) in clinical
setting is important for measuring the efficacy of drugs and their safety and in
personalizing drug therapy. We investigated the levels of AED, carbamazepine
(CBZ), phenytoin (PHT) and phenobarbital (PHB), to understand their association
in saliva compared with those in serum during the therapy. MATERIALS AND METHODS:
In this study, we performed a prospective study of 116 persons with epilepsy
(PWE; mean age 26.90 +/- 11.83 years). Serum and saliva samples were collected at
trough levels from the patients, who were under the treatment of CBZ, PHT and PHB
either alone or in combination of these drugs for at least three months. The drug
levels were assessed by high-performance liquid chromatography. RESULTS AND
CONCLUSIONS: The number of males (n = 88; 75.86%) was higher than females (n =
28; 24.14%) among the recruited patients. The intake of CBZ, PHT and PHB was
observed in 49.14%, 68.10% and 38.79% of PWE, respectively. The levels of these
AEDs showed a significant correlation (p < 0.05) between serum and saliva.
Interestingly, the levels of mono-therapy or bi-therapy showed a significant
association (p < 0.05) between serum and saliva, however, there was no
significant association in case of poly-therapy. This is the first report in the
Indian population on simultaneous estimation of the three commonly used AEDs,
such as CBZ, PHT and PHB in serum and saliva implicating their associations,
either in mono-therapy or bi-therapy in PWE.
PMID- 26441315
TI - Cyclic fatigue resistance of ProTaper Next nickel-titanium rotary files.
PMID- 26441314
TI - Exploring autistic-like traits relating to empathic attitude and psychological
distress in hospital pharmacists.
AB - BACKGROUND: Pharmacists are expected to play a key role in modern cancer care.
Research suggests that an empathic approach and attitude in medical staff
improves the quality of patient care. An empathic attitude and psychological
distress are thought to be associated with autistic-like traits, but little is
known about such traits. OBJECTIVE: In this study, we aimed to clarify the
associations among autistic-like traits, empathic attitude in a medical context,
and psychological health in hospital pharmacists. SETTING: Eligibility criteria
for inclusion were certified pharmacists working at hospitals for patient care
who returned their questionnaires. METHOD: Eight hundred and twenty-three
hospital pharmacists completed a number of self-administered questionnaires
anonymously by mail. MAIN OUTCOME MEASURES: Scores were obtained on the Autism
Spectrum Quotient, the Jefferson Scale of Empathy, the General Health
Questionnaire-12, and subscales of the Interpersonal Reactivity Index
(Perspective Taking, IRI-Empathic Concern, IRIPersonal Distress). We performed
correlation and mediation analyses to confirm that the empathy and general health
questionnaires were associated with autism-spectrum quotient scores, and with
each IRI subscale. RESULTS: Complete responses were obtained from 379 pharmacists
comprising 151 males (39.8 %) with a mean age of 37.7 +/- 10.8 years (missing
data, n = 13) and a median of 11 years after qualification as a pharmacist.
Autism-Spectrum Quotient scores were inversely correlated with empathy (r =
0.22, p < 0.001) and positively correlated with general health scores (r = 0.40,
p < 0.001). In the models with mediation, the inverse correlation between autism
spectrum quotient and empathy scores was mediated indirectly by IRI-Perspective
Taking and IRI-Empathic Concern, and the positive correlation between autism
spectrum quotient and general health was mediated indirectly by IRI-Personal
Distress. There were also direct effects, with significant effects of autism
spectrum quotient on empathy and general health scores. CONCLUSION: Our findings
suggest that autistic-like traits affect both empathic attitude in a medical
context and the psychological health of pharmacists. We recommend that to improve
empathy in those with high levels of autistic-like traits, we may need to develop
specialized interventions, such as improving communication skills training.
PMID- 26441316
TI - Response: Cyclic fatigue resistance of ProTaper Next nickel-titanium rotary
instruments.
PMID- 26441317
TI - Corrigendum.
PMID- 26441318
TI - Prospective case-controlled sound localisation study after cochlear implantation
in adults with single-sided deafness and ipsilateral tinnitus.
AB - OBJECTIVES: To analyse the sound localisation skills of subjects with profound
single-sided deafness (SSD) and accompanied ipsilateral tinnitus who are using a
cochlear implant (CI) for between 4 and 11 years. DESIGN: Sound localisation
skills were tested using nine loudspeakers in a frontal semicircle ranging from
90 degrees to +90 degrees . Subjects were tested in the CION and the CIOFF
conditions via 3 localisation stimuli: broadband noise (BB), low-pass noise (LP)
and high-pass noise (HP). PARTICIPANTS: The test group consisted of 10 adult
subjects with profound sensorineural SSD, ipsilateral tinnitus and a CI.
Normative data of a control group of 30 normal hearing subjects were used for
comparison. MAIN OUTCOME MEASURES: Sound location accuracy was analysed via the
root-mean-square error (RMSE), the mean absolute error (MAE), the localisation
bias ('b') and the bias-adjusted deviation ('db '). Subjective dynamic aspects of
hearing were assessed via a reduced version of the Speech, Spatial and Qualities
of Hearing Scale (SSQ5 ). RESULTS: For all 3 stimuli, the RMSE improved
significantly in SSD subjects in the CION condition compared to the CIOFF
condition. The localisation accuracy of subjects with SSD improved significantly
for BB and HP stimuli. A significant bias-adjusted deviation 'db ' was found for
the BB and HP stimuli. Subjects' mean SSQ5 scores were significantly higher in
the CION condition at test date than in the CIOFF condition preoperatively.
CONCLUSIONS: Subjects can better locate sound in the CION condition than in the
CIOFF condition.
PMID- 26441319
TI - [Erratum to: The German Acanthamoeba keratitis register : Initial results of a
multicenter study].
PMID- 26441320
TI - Sobriety Treatment and Recovery Teams: Implementation Fidelity and Related
Outcomes.
AB - BACKGROUND: Although integrated programs between child welfare and substance
abuse treatment are recommended for families with co-occurring child maltreatment
and substance use disorders, implementing integrated service delivery strategies
with fidelity is a challenging process. OBJECTIVE: This study of the first five
years of the Sobriety Treatment and Recovery Team (START) program examines
implementation fidelity using a model proposed by Carroll et al. (2007). The
study describes the process of strengthening moderators of implementation
fidelity, trends in adherence to START service delivery standards, and trends in
parent and child outcomes. METHODS: Qualitative and quantitative measures were
used to prospectively study three START sites serving 341 families with 550
parents and 717 children. RESULTS: To achieve implementation fidelity to service
delivery standards required a pre-service year and two full years of operation,
persistent leadership, and facilitative actions that challenged the existing
paradigm. Over four years of service delivery, the time from the child protective
services report to completion of five drug treatment sessions was reduced by an
average of 75 days. This trend was associated with an increase in parent
retention, parental sobriety, and parent retention of child custody.
Conclusions/Importance: Understanding the implementation processes necessary to
establish complex integrated programs may support realistic allocation of
resources. Although implementation fidelity is a moderator of program outcome,
complex inter-agency interventions may benefit from innovative measures of
fidelity that promote improvement without extensive cost and data collection
burden. The implementation framework applied in this study was useful in
examining implementation processes, fidelity, and related outcomes.
PMID- 26441322
TI - ZNF1 Encodes a Putative C2H2 Zinc-Finger Protein Essential for Appressorium
Differentiation by the Rice Blast Fungus Magnaporthe oryzae.
AB - The rice blast fungus Magnaporthe oryzae forms specialized infection structures
called appressoria which are essential for gaining entry to plant tissue. Here,
we report the identification of a novel nonpathogenic T-DNA-tagged mutant XF696
of M. oryzae with a single insertion in the promoter of ZNF1, which encodes a
putative transcription factor (TF). Targeted gene deletion mutants of ZNF1 are
nonpathogenic and unable to develop appressoria. However, Deltaznf1 mutants still
respond to exogenous cyclic AMP on hydrophilic surfaces and can sense hydrophobic
surfaces, initiating the differentiation of germ tubes. Interestingly, Deltaznf1
mutants also produce significantly more conidia compared with the isogenic wild
type strain. Quantitative reverse-transcription polymerase chain reaction
analysis and green fluorescent protein fusion experiments revealed that
expression of ZNF1 was highly induced during germination and appressorium
development in M. oryzae and potentially regulated by the Pmk1 mitogen-activated
protein kinase pathway. We observed that Deltaznf1 mutants are affected in
mitosis and impaired in mobilization and degradation of lipid droplets and
glycogen reserves during appressorium differentiation. Site-directed mutagenesis
confirmed that three of the four C2H2 zinc-finger domains are essential for the
function of Znf1. Taken together, we conclude that a C2H2 zinc-finger TF encoded
by ZNF1 is essential for appressorium development by the rice blast fungus.
PMID- 26441321
TI - Spatial patterns of atrophy, hypometabolism, and amyloid deposition in
Alzheimer's disease correspond to dissociable functional brain networks.
AB - Recent neuroimaging studies of Alzheimer's disease (AD) have emphasized
topographical similarities between AD-related brain changes and a prominent
cortical association network called the default-mode network (DMN). However, the
specificity of distinct imaging abnormalities for the DMN compared to other
intrinsic connectivity networks (ICNs) of the limbic and heteromodal association
cortex has not yet been examined systematically. We assessed regional amyloid
load using AV45-PET, neuronal metabolism using FDG-PET, and gray matter volume
using structural MRI in 473 participants from the Alzheimer's Disease
Neuroimaging Initiative, including preclinical, predementia, and clinically
manifest AD stages. Complementary region-of-interest and voxel-based analyses
were used to assess disease stage- and modality-specific changes within seven
principle ICNs of the human brain as defined by a standardized functional
connectivity atlas. Amyloid deposition in AD dementia showed a preference for the
DMN, but high effect sizes were also observed for other neocortical ICNs, most
notably the frontoparietal-control network. Atrophic changes were most specific
for an anterior limbic network, followed by the DMN, whereas other neocortical
networks were relatively spared. Hypometabolism appeared to be a mixture of both
amyloid- and atrophy-related profiles. Similar patterns of modality-dependent
network specificity were also observed in the predementia and, for amyloid
deposition, in the preclinical stage. These quantitative data confirm a high
vulnerability of the DMN for multimodal imaging abnormalities in AD. However,
rather than being selective for the DMN, imaging abnormalities more generally
affect higher order cognitive networks and, importantly, the vulnerability
profiles of these networks markedly differ for distinct aspects of AD pathology.
PMID- 26441323
TI - Penetration Peg Formation and Invasive Hyphae Development Require Stage-Specific
Activation of MoGTI1 in Magnaporthe oryzae.
AB - The hemibiotrophic pathogen Magnaporthe oryzae causes one of the most destructive
diseases in cultivated rice. Complex infection-related morphogenesis and
production of various effectors are known to be important for successful
colonization and disease development. In this study, we characterized the
activation of the MoGTI1 transcription factor and its role in infection-related
morphogenesis and effector gene expression. The Mogti1 mutant was nonpathogenic,
although it was normal in appressorium formation and turgor generation. Close
examination showed that Mogti1 was defective in penetration and growth of normal
invasive hyphae. Deletion of MoGTI1 affected the expression of the majority of
effector genes. The expression of MoGti1 appeared to be controlled by the Mps1
but not Pmk1 mitogen-activated protein kinase (MAPK), and the mps1 and Mogti1
mutants had similar phenotypes in plant infection and cell wall integrity
defects. However, lack of MAPK phosphorylation sites and dispensability of the
putative MAPK docking site suggested that MoGti1 is not a direct target of Mps1.
Site-specific mutagenesis analyses showed that the putative protein kinase A
phosphorylation site was not essential for localization of MoGti1 to the nucleus
but important for its normal function. Although the cyclin-dependent kinase (CDK)
phosphorylation site of MoGti1 is dispensable during vegetative growth and
appressorium formation, the S77A mutation affected penetration and invasive
growth. Localization of MoGti1(S77A)-green fluorescent protein to the nucleus in
late stages of appressorium formation and during invasive growth was not
observed, suggesting a stage-specific CDK phosphorylation of MoGti1. Overall, our
data indicate that Mps1 may indirectly regulate the expression of MoGti1 in
maintaining cell wall integrity, conidiation, and plant infection. MoGti1 is
likely a stage-specific target of CDK and plays a crucial role in effector gene
expression and morphogenesis related to the development of penetration pegs and
invasive hyphae.
PMID- 26441324
TI - Surface Model and Tomographic Archive of Fossil Primate and Other Mammal Holotype
and Paratype Specimens of the Ditsong National Museum of Natural History,
Pretoria, South Africa.
AB - Nearly a century of paleontological excavation and analysis from the cave
deposits of the Cradle of Humankind UNESCO World Heritage Site in northeastern
South Africa underlies much of our understanding of the evolutionary history of
hominins, other primates and other mammal lineages in the late Pliocene and early
Pleistocene of Africa. As one of few designated fossil repositories, the Plio
Pleistocene Palaeontology Section of the Ditsong National Museum of Natural
History (DNMNH; the former Transvaal Museum) curates much of the mammalian faunas
recovered from the fossil-rich deposits of major South African hominin-bearing
localities, including the holotype and paratype specimens of many primate,
carnivore, and other mammal species (Orders Primates, Carnivora, Artiodactyla,
Eulipotyphla, Hyracoidea, Lagomorpha, Perissodactyla, and Proboscidea). Here we
describe an open-access digital archive of high-resolution, full-color three
dimensional (3D) surface meshes of all 89 non-hominin holotype, paratype and
significant mammalian specimens curated in the Plio-Pleistocene Section vault.
Surface meshes were generated using a commercial surface scanner (Artec Spider,
Artec Group, Luxembourg), are provided in formats that can be opened in both open
source and commercial software, and can be readily downloaded either via an
online data repository (MorphoSource) or via direct request from the DNMNH. In
addition to providing surface meshes for each specimen, we also provide
tomographic data (both computerized tomography [CT] and microfocus [microCT]) for
a subset of these fossil specimens. This archive of the DNMNH Plio-Pleistocene
collections represents the first research-quality 3D datasets of African mammal
fossils to be made openly available. This simultaneously provides the
paleontological community with essential baseline information (e.g., updated
listing and 3D record of specimens in their current state of preservation) and
serves as a single resource of high-resolution digital data that improves
collections accessibility, reduces unnecessary duplication of efforts by
researchers, and encourages ongoing imaging-based paleobiological research across
a range of South African non-hominin fossil faunas. Because the types, paratypes,
and key specimens include globally-distributed mammal taxa, this digital archive
not only provides 3D morphological data on taxa fundamental to Neogene and
Quaternary South African palaeontology, but also lineages critical to research on
African, other Old World, and New World paleocommunities. With such a broader
impact of the DNMNH 3D data, we hope that establishing open access to this
digital archive will encourage other researchers and institutions to provide
similar resources that increase accessibility to paleontological collections and
support advanced paleobiological analyses.
PMID- 26441325
TI - ITPA Polymorphisms Are Associated with Hematological Side Effects during
Antiviral Therapy for Chronic HCV Infection.
AB - BACKGROUND/OBJECTIVE: Genetic polymorphisms in the inosine triphosphatase (ITPA)
gene have been associated with the protection from early ribavirin(RBV)-induced
hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection.
The aim of the present study was to investigate the association between the
functional ITPA variants and hematological side effects during antiviral therapy
with pegylated interferon (PegIFN) and RBV. PATIENTS AND METHODS: This cohort
study included all consecutive Caucasian patients treated for chronic HCV
infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was
available for genetic testing. The predicted inosine triphosphate pyrophosphatase
(ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101.
Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions,
blood transfusions and use of erythropoietin were assessed. RESULTS: In total,
213 patients were included. The predicted ITPase activity was normal among 152
(71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear
regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and
normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with
more Hb decline at week 4 of treatment. Patients with normal ITPase activity
underwent more dose adjustments of RBV than patients with ITPase deficiency
(19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%)
vs 0 (0%),p = 0.024). CONCLUSION: Genetic variants in the ITPA gene protected
against RBV treatment-induced anemia among Caucasian patients with chronic HCV
infection. Patients with normal ITPase activity underwent more dose reductions of
RBV and received erythropoietin more frequently.
PMID- 26441326
TI - A light-regulated bZIP module, photozipper, induces the binding of fused proteins
to the target DNA sequence in a blue light-dependent manner.
AB - Aureochrome-1 (AUREO1) has been identified as a blue light (BL) receptor
responsible for the BL-induced blanching of a stramenopile alga, Vaucheria
frigida. BL induces the dimerization of monomeric AUREO1, which subsequently
increases its affinity for the target sequence. We made a synthetic gene encoding
N-terminally truncated monomeric AUREO1 (Photozipper protein) containing a basic
region/leucine zipper (bZIP) domain and a light-oxygen-voltage-sensing domain. In
the present study, yellow fluorescent protein or mCherry protein was fused with
the Photozipper (PZ) protein, and their oligomeric structures and DNA-binding
were compared in the dark and light states. Dynamic light scattering and size
exclusion chromatography demonstrated that the hydrodynamic radii and molecular
masses of the fusion proteins increased upon BL illumination, suggesting that
fusion PZs underwent BL-induced dimerization. Moreover, BL-induced dimerization
enhanced their affinities for the target sequence. Taken together, PZ likely
functions as a BL-regulated bZIP module in fusion proteins, and can possibly
provide a new approach for controlling bZIP transcription factors.
PMID- 26441328
TI - In Absentia: An Exploratory Study of How Patients Are Considered in
Multidisciplinary Cancer Team Meetings.
AB - BACKGROUND: Multidisciplinary team meetings and shared decision-making are
potential means of delivering patient-centred care. Not much is known about how
those two paradigms fit together in cancer care. This study aimed to investigate
how decisions are made in multidisciplinary team meetings and whether patient
perspectives are incorporated in these decisions. MATERIALS AND METHODS: A
qualitative study was conducted using non-participant observation at
multidisciplinary team meetings (also called tumor boards) at the University
Cancer Center Hamburg-Eppendorf, Germany. Two researchers recorded structured
field notes from a total of N = 15 multidisciplinary team meetings. Data were
analyzed using content analysis and descriptive statistics. RESULTS: Physicians
mainly exchanged medical information and based their decision-making on this
information. Individual patient characteristics or their treatment preferences
were rarely considered or discussed. In the few cases where patient preferences
were raised as a topic, this information did not seem to be taken into account in
decision-making processes about treatment recommendations. CONCLUSION: The
processes in multidisciplinary team meetings we observed did not exhibit shared
decision-making. Patient perspectives were absent. If multidisciplinary team
meetings wish to become more patient-centred they will have to modify their
processes and find a way to include patient preferences into the decision-making
process.
PMID- 26441327
TI - Neuropeptide Y: A stressful review.
AB - Stress is defined as an adverse condition that disturbs the homeostasis of the
body and activates adaptation responses. Among the many pathways and mediators
involved, neuropeptide Y (NPY) stands out due to its unique stress-relieving,
anxiolytic and neuroprotective properties. Stress exposure alters the
biosynthesis of NPY in distinct brain regions, the magnitude and direction of
this effect varying with the duration and type of stress. NPY is expressed in
particular neurons of the brainstem, hypothalamus and limbic system, which
explains why NPY has an impact on stress-related changes in emotional-affective
behaviour and feeding as well as on stress coping. The biological actions of NPY
in mammals are mediated by the Y1, Y2, Y4 and Y5 receptors, Y1 receptor
stimulation being anxiolytic whereas Y2 receptor activation is anxiogenic.
Emerging evidence attributes NPY a role in stress resilience, the ability to cope
with stress. Thus there is a negative correlation between stress-induced
behavioural disruption and cerebral NPY expression in animal models of post
traumatic stress disorder. Exogenous NPY prevents the negative consequences of
stress, and polymorphisms of the NPY gene are predictive of impaired stress
processing and increased risk of neuropsychiatric diseases. Stress is also a
factor contributing to, and resulting from, neurodegenerative diseases such as
Alzheimer's, Parkinson's and Huntington's disease, in which NPY appears to play
an important neuroprotective role. This review summarizes the evidence for an
implication of NPY in stress-related and neurodegenerative pathologies and
addresses the cerebral NPY system as a therapeutic target.
PMID- 26441329
TI - Tibial baseplate positioning in robotic-assisted and conventional
unicompartmental knee arthroplasty.
AB - This study compared tibial baseplate alignment (TBA) between robotic-arm-assisted
(RAA) and conventional (CONV) unicompartmental knee arthroplasties (UKAs). We
hypothesized that RAA would increase the percentage of implants within a
predetermined safe zone (SZ). We identified 177 CONV and 87 RAA UKAs through our
center's patient registry. Two individuals reviewed postoperative knee
radiographs and determined TBA. Coronal baseplate positioning was more accurate
(i.e., within the SZ) for RAA (2.6 degrees +/- 1.5 degrees vs. 3.9 degrees +/-
2.4 degrees , p < 0. 0001). Conversely, sagittal alignment was more accurate for
CONV (4.9 degrees +/- 2.8 degrees vs. 2.4 degrees +/- 1.6 degrees , p <
0.0001). RAA was more precise in both planes (p < 0.0001). There was no
difference in the percentage of implants within the SZ between the two groups (p
= 1.0).
PMID- 26441330
TI - Prospective multicentre study of the clinical and functional outcomes following
quadriceps tendon repair with suture anchors.
AB - INTRODUCTION: Quadriceps tendon avulsions are typically treated by reattaching
the tendon through bone tunnels, with or without tendon or hardware augmentation.
The operated knee joint can be moved right away; however, tendon grafting or
tension banding will be required to protect the repair, and the hardware must be
removed later on. The goal of this study was to evaluate the clinical and
functional outcomes when suture anchors are used to reattached torn quadriceps
tendon, and also to assess tendon healing using MRI. MATERIALS AND METHODS:
Thirteen consecutive patients with avulsed quadriceps tendons were operated and
then followed prospectively. The surgical technique consisted of tendon
reattachment using at least three anchors, in addition to intratendinous weaving
of the sutures. Weight bearing was allowed while using a splint. Rehabilitation
was initiated immediately after surgery according to a set protocol. RESULTS:
Eleven patients were followed for a mean of 14.7 months. Two retears occurred in
patients who did not wear the splint. Eighty-two per cent of patients were
satisfied or very satisfied with the outcome. The mean knee flexion was 124.5
degrees . All patients were able to return to their pre-injury activity levels.
The mean time for clinical and functional recovery was 3 months. MRI performed 6
months after the surgical repair revealed good tendon healing. DISCUSSION: This
was the first prospective study performed on quadriceps avulsion patients
undergoing suture anchor repair. Prior clinical case reports have shown that this
method leads to predictable clinical and functional results. Our results were
comparable to those in published cases. CONCLUSION: The procedure is simpler when
only suture anchors are used. Tendon healing was observed on MRI in all cases.
This simple, reproducible technique is free of the drawbacks associated with the
typical repair augmentation.
PMID- 26441333
TI - miRNAs: early prognostic biomarkers for Type 2 diabetes mellitus?
AB - Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and is
associated with peripheral insulin resistance. The currently used therapies aim
to delay progression of T2DM. Their efficacy could drastically be improved if
implemented at earlier stages. Classical diagnostic markers (blood glucose and
HbA1C) are generally detected once metabolic imbalance has already set in.
Therefore, development of biomarkers for early diagnosis would help identify
individuals at risk for developing T2DM. Along with genetic predisposition,
epigenetics also plays a major role in T2DM development. In this review, we
discuss the potential role of early diagnostic markers such as circulating
miRNAs, studies done so far and challenges to be considered while taking into
account the novel role of miRNAs as prognostic biomarkers.
PMID- 26441331
TI - TGF-beta1 Reduces miR-29a Expression to Promote Tumorigenicity and Metastasis of
Cholangiocarcinoma by Targeting HDAC4.
AB - Transforming growth factor beta1 (TGF-beta1) and miRNAs play important roles in
cholangiocarcinoma progression. In this study, miR-29a level was found
significantly decreased in both cholangiocarcinoma tissues and tumor cell lines.
TGF-beta1 reduced miR-29a expression in tumor cell lines. Furthermore, anti-miR
29a reduced the proliferation and metastasis capacity of cholangiocarcinoma cell
lines in vitro, overexpression of miR-29a counteracted TGF-beta1-mediated cell
growth and metastasis. Subsequent investigation identified HDAC4 is a direct
target of miR-29a. In addition, restoration of HDAC4 attenuated miR-29a-mediated
inhibition of cell proliferation and metastasis. CONCLUSIONS: TGF-beta1/miR
29a/HDAC4 pathway contributes to the pathogenesis of cholangiocarcinoma and our
data provide new therapeutic targets for cholangiocarcinoma.
PMID- 26441332
TI - Reduced error signalling in medication-naive children with ADHD: associations
with behavioural variability and post-error adaptations.
AB - BACKGROUND: We examined the blood-oxygen level-dependent (BOLD) activation in
brain regions that signal errors and their association with intraindividual
behavioural variability and adaptation to errors in children with attention
deficit/hyperactivity disorder (ADHD). METHODS: We acquired functional MRI data
during a Flanker task in medication-naive children with ADHD and healthy controls
aged 8-12 years and analyzed the data using independent component analysis. For
components corresponding to performance monitoring networks, we compared
activations across groups and conditions and correlated them with reaction times
(RT). Additionally, we analyzed post-error adaptations in behaviour and motor
component activations. RESULTS: We included 25 children with ADHD and 29 controls
in our analysis. Children with ADHD displayed reduced activation to errors in
cingulo-opercular regions and higher RT variability, but no differences of
interference control. Larger BOLD amplitude to error trials significantly
predicted reduced RT variability across all participants. Neither group showed
evidence of post-error response slowing; however, post-error adaptation in motor
networks was significantly reduced in children with ADHD. This adaptation was
inversely related to activation of the right-lateralized ventral attention
network (VAN) on error trials and to task-driven connectivity between the cingulo
opercular system and the VAN. LIMITATIONS: Our study was limited by the modest
sample size and imperfect matching across groups. CONCLUSION: Our findings show a
deficit in cingulo-opercular activation in children with ADHD that could relate
to reduced signalling for errors. Moreover, the reduced orienting of the VAN
signal may mediate deficient post-error motor adaptions. Pinpointing general
performance monitoring problems to specific brain regions and operations in error
processing may help to guide the targets of future treatments for ADHD.
PMID- 26441334
TI - Temperature Calibration for In Situ Environmental Transmission Electron
Microscopy Experiments.
AB - In situ environmental transmission electron microscopy (ETEM) experiments require
specimen heating holders to study material behavior in gaseous environments at
elevated temperatures. In order to extract meaningful kinetic parameters, such as
activation energies, it is essential to have a direct and accurate measurement of
local sample temperature. This is particularly important if the sample
temperature might fluctuate, for example when room temperature gases are
introduced to the sample area. Using selected-area diffraction (SAD) in an ETEM,
the lattice parameter of Ag nanoparticles was measured as a function of the
temperature and pressure of hydrogen gas to provide a calibration of the local
sample temperature. SAD permits measurement of temperature to an accuracy of +/
30 degrees C using Ag lattice expansion. Gas introduction can cause sample
cooling of several hundred degrees celsius for gas pressures achievable in the
ETEM.
PMID- 26441335
TI - Evaluation of X-ray doses and their corresponding biological effects on
experimental animals in cone-beam micro-CT scans (R-mCT2).
AB - Studies show that the radiation dose received during a micro-CT examination may
have adverse effects on living subjects. However, the correlations between the
biological effects and the radiation doses have never been thoroughly evaluated
in the majority of cases. In this study, we evaluated the biological radiation
effects of measured radiation doses in ICR mice using cone-beam micro-CT scans.
Long-term in vivo whole-body micro-CT scans of ICR mice were performed for a
duration of 4 weeks. Although a scanning frequency of three scans per week is
higher than that necessary for conventional studies, this study represents
particular cases where the subjects may undergo an extreme number of
examinations. The average X-ray dose of a CT scan measures 16.19 mGy at the
center of a phantom and 16.24 mGy at an offset position of 7.5 mm from the center
of the phantom. The total average dose at the center of the phantom during the 4
week scanning period was 194.3 mGy. No significant radiation effects were
observed in the weight gain curves, organ weights, blood analyses, litter sizes,
reared offspring sizes, and the histopathologic results. Therefore, it is
unlikely that the measured doses for the CT scans caused any radiation damage in
the mice.
PMID- 26441337
TI - Molecular networks: Protein droplets in the spotlight.
PMID- 26441336
TI - Increased basophil activation in adult patients with anaphylaxis.
PMID- 26441338
TI - Development: Ubiquitylation determines cell fate.
PMID- 26441339
TI - Assessing the potential for intrinsic recovery in a Collembola two-generation
study: possible implementation in a tiered soil risk assessment approach for
plant protection products.
AB - Collembola are soil dwelling organisms that provide important ecosystem services
within soils. To increase realism in evaluating potential effects of plant
protection products a Collembola two-generation study was developed. This test
assesses the potential for recovery of Collembola when exposed to plant
protection products. Juvenile individuals of Folsomia candida (Willem, Ann Soc
Entomol Belg 46:275-283, 1902) which hatched under conditions of exposure to a
test substance in a modified OECD 232 bioassay were introduced into a second
consecutive bioassay containing the same test substance aged in soil. This test
system determines whether a population which was initially impacted by a
substance in a 1st bioassay shows normal reproduction or survival in a 2nd
bioassay after aging of the test substance in soil. An intermediate period for
juvenile growth is included between the 1st and 2nd bioassay in order to reduce
the control treatment variability in reproduction and mortality to fulfill the
validity criteria according to the OECD 232 guideline. The Collembola two
generation study is able to differentiate between substances showing either a
potential long-term risk or comprising a low risk. Comparing the results of this
two generation study with data from semi-field or field studies indicates a high
degree of conservatism when this test is considered within a tiered risk
assessment scheme. This approach represents a valuable tool which makes the risk
assessment more efficient by providing an alternative refinement option for
highly conservative tier 1 Collembola risk assessment.
PMID- 26441340
TI - Diagnostic Value of the Combination of Golgi Protein 73 and Alpha-Fetoprotein in
Hepatocellular Carcinoma: A Meta-Analysis.
AB - Conflicting results have been widely reported on the use of Golgi protein 73
(GP73) as a serum biomarker for diagnosing hepatocellular carcinoma (HCC). This
study evaluated the accuracy of GP73, alpha-fetoprotein (AFP), and GP73 + AFP for
diagnosing HCC. The meta-analysis was performed on 11 studies that were selected
by means of a comprehensive systematic literature review. Summary diagnostic
accuracy, meta-regression analysis for heterogeneity and publication bias, and
other statistical analyses were performed using Meta-Disc (version 1.4) and Stata
(version 12.0). Pooled sensitivity, specificity, and diagnostic odds ratio were
0.77 (95% CI: 0.75-0.79), 0.91 (95% CI: 0.90-0.92), and 12.49 (95% CI: 4.91
31.79) for GP73; 0.62 (95% CI: 0.60-0.64), 0.84 (95% CI: 0.83-0.85), and 11.61
(95% CI: 8.02-16.81) for AFP; and 0.87 (95% CI: 0.85-0.89), 0.85 (95% CI: 0.84
0.86), and 30.63 (95% CI: 18.10-51.84) for GP73 + AFP. The area under the curve
values were 0.86, 0.84, and 0.91 for GP73, AFP, and GP73 + AFP, respectively.
These results indicate that for HCC diagnosis, the accuracy of GP73 was higher
than that of AFP, and that GP73 + AFP exhibited significantly higher diagnostic
accuracy than did GP73 or AFP alone.
PMID- 26441342
TI - Combining 3D Hydraulic Tomography with Tracer Tests for Improved Transport
Characterization.
AB - Hydraulic tomography (HT) is a method for resolving the spatial distribution of
hydraulic parameters to some extent, but many details important for solute
transport usually remain unresolved. We present a methodology to improve solute
transport predictions by combining data from HT with the breakthrough curve (BTC)
of a single forced-gradient tracer test. We estimated the three dimensional (3D)
hydraulic-conductivity field in an alluvial aquifer by inverting tomographic
pumping tests performed at the Hydrogeological Research Site Lauswiesen close to
Tubingen, Germany, using a regularized pilot-point method. We compared the
estimated parameter field to available profiles of hydraulic-conductivity
variations from direct-push injection logging (DPIL), and validated the hydraulic
conductivity field with hydraulic-head measurements of tests not used in the
inversion. After validation, spatially uniform parameters for dual-domain
transport were estimated by fitting tracer data collected during a forced
gradient tracer test. The dual-domain assumption was used to parameterize effects
of the unresolved heterogeneity of the aquifer and deemed necessary to fit the
shape of the BTC using reasonable parameter values. The estimated hydraulic
conductivity field and transport parameters were subsequently used to
successfully predict a second independent tracer test. Our work provides an
efficient and practical approach to predict solute transport in heterogeneous
aquifers without performing elaborate field tracer tests with a tomographic
layout.
PMID- 26441341
TI - Primary Visual Cortex as a Saliency Map: A Parameter-Free Prediction and Its Test
by Behavioral Data.
AB - It has been hypothesized that neural activities in the primary visual cortex (V1)
represent a saliency map of the visual field to exogenously guide attention. This
hypothesis has so far provided only qualitative predictions and their
confirmations. We report this hypothesis' first quantitative prediction, derived
without free parameters, and its confirmation by human behavioral data. The
hypothesis provides a direct link between V1 neural responses to a visual
location and the saliency of that location to guide attention exogenously. In a
visual input containing many bars, one of them saliently different from all the
other bars which are identical to each other, saliency at the singleton's
location can be measured by the shortness of the reaction time in a visual search
for singletons. The hypothesis predicts quantitatively the whole distribution of
the reaction times to find a singleton unique in color, orientation, and motion
direction from the reaction times to find other types of singletons. The
prediction matches human reaction time data. A requirement for this successful
prediction is a data-motivated assumption that V1 lacks neurons tuned
simultaneously to color, orientation, and motion direction of visual inputs.
Since evidence suggests that extrastriate cortices do have such neurons, we
discuss the possibility that the extrastriate cortices play no role in guiding
exogenous attention so that they can be devoted to other functions like visual
decoding and endogenous attention.
PMID- 26441343
TI - MiR-302/367 regulate neural progenitor proliferation, differentiation timing, and
survival in neurulation.
AB - How neural progenitor cell (NPC) behaviors are temporally controlled in early
developing embryos remains undefined. The in vivo functions of microRNAs (miRNAs)
in early mammalian development remain largely unknown. Mir-302/367 is a miRNA
cluster that encodes miR-367 and four miR-302 members (miR302a-d). We show that
miR-302b is highly expressed in early neuroepithelium and its expression decline
as development progresses. We generated a mir-302/367 knockout mouse model and
found that deletion of mir-302/367 results in an early embryonic lethality and
open neural tube defect (NTD). NPCs exhibit enhanced proliferation, precocious
differentiation, and decreased cell survival in mutant embryos. Furthermore, we
identified Fgf15, Cyclin D1, and D2 as direct targets of miR-302 in NPCs in vivo,
and their expression is enhanced in mutant NPCs. Ectopic expression of Cyclin D1
and D2 increases NPC proliferation, while FGF19 (human ortholog of Fgf15)
overexpression leads to an increase of NPC differentiation. Thus, these findings
reveal essential roles of miR-302/367 in orchestrating gene expression and NPC
behaviors in neurulation; they also point to miRNAs as critical genetic
components associated with neural tube formation.
PMID- 26441345
TI - Thyroid Cancer Detection by Ultrasound Among Residents Ages 18 Years and Younger
in Fukushima, Japan: 2011 to 2014.
AB - BACKGROUND: After the Great East Japan Earthquake and Tsunami in March 2011,
radioactive elements were released from the Fukushima Daiichi Nuclear Power
Plant. Based on prior knowledge, concern emerged about whether an increased
incidence of thyroid cancer among exposed residents would occur as a result.
METHODS: After the release, Fukushima Prefecture performed ultrasound thyroid
screening on all residents ages <=18 years. The first round of screening included
298,577 examinees, and a second round began in April 2014. We analyzed the
prefecture results from the first and second round up to December 31, 2014, in
comparison with the Japanese annual incidence and the incidence within a
reference area in Fukushima Prefecture. RESULTS: The highest incidence rate
ratio, using a latency period of 4 years, was observed in the central middle
district of the prefecture compared with the Japanese annual incidence (incidence
rate ratio = 50; 95% confidence interval [CI] = 25, 90). The prevalence of
thyroid cancer was 605 per million examinees (95% CI = 302, 1,082) and the
prevalence odds ratio compared with the reference district in Fukushima
Prefecture was 2.6 (95% CI = 0.99, 7.0). In the second screening round, even
under the assumption that the rest of examinees were disease free, an incidence
rate ratio of 12 has already been observed (95% CI = 5.1, 23). CONCLUSIONS: An
excess of thyroid cancer has been detected by ultrasound among children and
adolescents in Fukushima Prefecture within 4 years of the release, and is
unlikely to be explained by a screening surge.
PMID- 26441346
TI - Efficient and Substantial DNA Lesions From Near 0 eV Electron-Induced Decay of
the O4-Hydrogenated Thymine Nucleotides: A DFT Study.
AB - Possible electron-induced ruptures of C3'-O3', C5'-O5', and N1-C1' bonds in O4
hydrogenated 2'-deoxythymidine-3'-monophosphate (3'-dT(O4H)MPH) and 2'
deoxythymidine-5'-monophosphate (5'-dT(O4H)MPH) are investigated using density
functional theory calculations, and efficient pathways are proposed. Electron
attachment causes remarkable structural relaxation in the thymine C6 site. A
concerted process of intramolecular proton transfer (IPT) from the C2' site of 2'
deoxyribose to the C6 site and the C3'-O3' bond rupture is observed in [3'
dT(O4H)MPH](-). A low activation barrier (9.32 kcal/mol) indicates that this
pathway is the most efficient one as compared to other known pathways leading to
backbone breaks of a single strand DNA at the non-3'-end thymine, which prevents
the N1-C1' bond cleavage in [3'-dT(O4H)MPH](-). However, essentially spontaneous
N1-C1' bond cleavage following similar IPT is predicted in [5'-dT(O4H)MPH](-). A
moderate activation barrier (13.02 kcal/mol) for the rate-controlling IPT step
suggests that base release from the N1-C1' cleavage arises readily at the 3'-end
of single strand DNA with the strand ended by a thymine. The C5'-O5' bond has
only an insignificant change in the IPT process. Solvent effects are found to
increase slightly the energy requirements for either bond ruptures (11.23
kcal/mol (C3'-O3') vs 16.18 kcal/mol (N1-C1')), but not change their relative
efficiencies.
PMID- 26441347
TI - IL-1beta promotes Th17 differentiation by inducing alternative splicing of FOXP3.
AB - CD4(+)FOXP3(+) regulatory T (Treg) cells are essential for maintaining
immunological self-tolerance. Treg cell development and function depend on the
transcription factor FOXP3, which is present in several distinct isoforms due to
alternative splicing. Despite the importance of FOXP3 in the proper maintenance
of Treg cells, the regulation and functional consequences of FOXP3 isoform
expression remains poorly understood. Here, we show that in human Treg cells IL
1beta promotes excision of FOXP3 exon 7. FOXP3 is not only expressed by Treg
cells but is also transiently expressed when naive T cells differentiate into
Th17 cells. Forced splicing of FOXP3 into FOXP3Delta2Delta7 strongly favored Th17
differentiation in vitro. We also found that patients with Crohn's disease
express increased levels of FOXP3 transcripts lacking exon 7, which correlate
with disease severity and IL-17 production. Our results demonstrate that
alternative splicing of FOXP3 modulates T cell differentiation. These results
highlight the importance of characterizing FOXP3 expression on an isoform basis
and suggest that immune responses may be manipulated by modulating the expression
of FOXP3 isoforms, which has broad implications for the treatment of autoimmune
diseases.
PMID- 26441348
TI - Mechanical strain determines the axis of planar polarity in ciliated epithelia.
AB - Epithelia containing multiciliated cells align beating cilia along a common
planar axis specified by the conserved planar cell polarity (PCP) pathway.
Specification of the planar axis is also thought to require a long-range cue to
align the axis globally, but the nature of this cue in ciliated and other
epithelia remains poorly understood. We examined this issue using the Xenopus
larval skin, where ciliary flow aligns to the anterior-posterior (A-P) axis. We
first show that a planar axis initially arises in the developing skin during
gastrulation, based on the appearance of polarized apical microtubules and cell
junctions with increased levels of stable PCP components. This axis also arises
in severely ventralized embryos, despite their deficient embryonic patterning.
Because ventralized embryos still gastrulate, producing a mechanical force that
strains the developing skin along the A-P axis, we asked whether this strain
alone drives global planar patterning. Isolated skin explanted before
gastrulation lacks strain and fails to acquire a global planar axis but responds
to exogenous strain by undergoing cell elongation, forming polarized apical
microtubules, and aligning stable components of the PCP pathway orthogonal to the
axis of strain. The planar axis in embryos can be redirected by applying
exogenous strain during a critical period around gastrulation. Finally, we
provide evidence that apical microtubules and the PCP pathway interact to align
the planar axis. These results indicate that oriented tissue strain generated by
the gastrulating mesoderm plays a major role in determining the global axis of
planar polarity of the developing skin.
PMID- 26441349
TI - All spiking, sustained ON displaced amacrine cells receive gap-junction input
from melanopsin ganglion cells.
AB - Retinal neurons exhibit sustained versus transient light responses, which are
thought to encode low- and high-frequency stimuli, respectively. This dichotomy
has been recognized since the earliest intracellular recordings from the 1960s,
but the underlying mechanisms are not yet fully understood. We report that in the
ganglion cell layer of rat retinas, all spiking amacrine interneurons with
sustained ON photoresponses receive gap-junction input from intrinsically
photosensitive retinal ganglion cells (ipRGCs), recently discovered
photoreceptors that specialize in prolonged irradiance detection. This input
presumably allows ipRGCs to regulate the secretion of neuromodulators from these
interneurons. We have identified three morphological varieties of such ipRGC
driven displaced amacrine cells: (1) monostratified cells with dendrites
terminating exclusively in sublamina S5 of the inner plexiform layer, (2)
bistratified cells with dendrites in both S1 and S5, and (3) polyaxonal cells
with dendrites and axons stratifying in S5. Most of these amacrine cells are wide
field, although some are medium field. The three classes respond to light
differently, suggesting that they probably perform diverse functions. These
results demonstrate that ipRGCs are a major source of tonic visual information
within the retina and exert widespread intraretinal influence. They also add to
recent evidence that ganglion cells signal not only to the brain.
PMID- 26441350
TI - Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental
Stability.
AB - Early transplantation and grafting experiments suggest that body organs follow
autonomous growth programs [1-3], therefore pointing to a need for coordination
mechanisms to produce fit individuals with proper proportions. We recently
identified Drosophila insulin-like peptide 8 (Dilp8) as a relaxin and insulin
like molecule secreted from growing tissues that plays a central role in
coordinating growth between organs and coupling organ growth with animal
maturation [4, 5]. Deciphering the function of Dilp8 in growth coordination
relies on the identification of the receptor and tissues relaying Dilp8
signaling. We show here that the orphan receptor leucine-rich repeat-containing G
protein-coupled receptor 3 (Lgr3), a member of the highly conserved family of
relaxin family peptide receptors (RXFPs), mediates the checkpoint function of
Dilp8 for entry into maturation. We functionally identify two Lgr3-positive
neurons in each brain lobe that are required to induce a developmental delay upon
overexpression of Dilp8. These neurons are located in the pars intercerebralis,
an important neuroendocrine area in the brain, and make physical contacts with
the PTTH neurons that ultimately control the production and release of the
molting steroid ecdysone. Reducing Lgr3 levels in these neurons results in adult
flies exhibiting increased fluctuating bilateral asymmetry, therefore
recapitulating the phenotype of dilp8 mutants. Our work reveals a novel
Dilp8/Lgr3 neuronal circuitry involved in a feedback mechanism that ensures
coordination between organ growth and developmental transitions and prevents
developmental variability.
PMID- 26441351
TI - A Multisensory Network for Olfactory Processing.
AB - Primary gustatory cortex (GC) is connected (both mono- and polysynaptically) to
primary olfactory (piriform) cortex (PC)-connections that might be hypothesized
to underlie the construction of a "flavor" percept when both gustatory and
olfactory stimuli are present. Here we use multisite electrophysiology and
optical inhibition of GC neurons (GCx, produced via infection with ArchT) to
demonstrate that, indeed, during gustatory stimulation, taste-selective
information is transmitted from GC to PC. We go on to show that these connections
impact olfactory processing even in the absence of gustatory stimulation: GCx
alters PC responses to olfactory stimuli presented alone, enhancing some and
eliminating others, despite leaving the path from nasal epithelium to PC intact.
Finally, we show the functional importance of this latter phenomenon,
demonstrating that GCx renders rats unable to properly recognize odor stimuli.
This sequence of findings suggests that sensory processing may be more
intrinsically integrative than previously thought.
PMID- 26441352
TI - Individual Aesthetic Preferences for Faces Are Shaped Mostly by Environments, Not
Genes.
AB - Although certain characteristics of human faces are broadly considered more
attractive (e.g., symmetry, averageness), people also routinely disagree with
each other on the relative attractiveness of faces. That is, to some significant
degree, beauty is in the "eye of the beholder." Here, we investigate the origins
of these individual differences in face preferences using a twin design, allowing
us to estimate the relative contributions of genetic and environmental variation
to individual face attractiveness judgments or face preferences. We first show
that individual face preferences (IP) can be reliably measured and are readily
dissociable from other types of attractiveness judgments (e.g., judgments of
scenes, objects). Next, we show that individual face preferences result primarily
from environments that are unique to each individual. This is in striking
contrast to individual differences in face identity recognition, which result
primarily from variations in genes [1]. We thus complete an etiological double
dissociation between two core domains of social perception (judgments of identity
versus attractiveness) within the same visual stimulus (the face). At the same
time, we provide an example, rare in behavioral genetics, of a reliably and
objectively measured behavioral characteristic where variations are shaped mostly
by the environment. The large impact of experience on individual face preferences
provides a novel window into the evolution and architecture of the social brain,
while lending new empirical support to the long-standing claim that environments
shape individual notions of what is attractive.
PMID- 26441353
TI - Sensory Feedback Reduces Individuality by Increasing Variability within Subjects.
AB - Behavioral variability is ubiquitous [1-6], yet variability is more than just
noise. Indeed, humans exploit their individual motor variability to improve
tracing and reaching tasks [7]. What controls motor variability? Increasing the
variability of sensory input, or applying force perturbations during a task,
increases task variability [8, 9]. Sensory feedback may also increase task
irrelevant variability [9, 10]. In contrast, sensory feedback during locust
flight or to multiple cortical areas just prior to task performance decreases
variability during task-relevant motor behavior [11, 12]. Thus, how sensory
feedback affects both task-relevant and task-irrelevant motor outputs must be
understood. Furthermore, since motor control is studied in populations, the
effects of sensory feedback on variability must also be understood within and
across subjects. For example, during locomotion, each step may vary within and
across individuals, even when behavior is normalized by step cycle duration [13].
Our previous work demonstrated that motor components that matter for effective
behavior show less individuality [14]. Is sensory feedback the mechanism for
reducing individuality? We analyzed durations and relative timings of motor pools
within swallowing motor patterns in the presence and absence of sensory feedback
and related these motor program components to behavior. Here, at the level of
identified motor neurons, we show that sensory feedback to motor program
components highly correlated with behavioral efficacy reduces variability across
subjects but-surprisingly-increases variability within subjects. By controlling
intrinsic, individual differences in motor neuronal activity, sensory feedback
provides each subject access to a common solution space.
PMID- 26441355
TI - Actin-Based Transport Adapts Polarity Domain Size to Local Cellular Curvature.
AB - Intracellular structures and organelles such as the nucleus, the centrosome, or
the mitotic spindle typically scale their size to cell size [1]. Similarly,
cortical polarity domains built around the active form of conserved Rho-GTPases,
such as Cdc42p, exhibit widths that may range over two orders of magnitudes in
cells with different sizes and shapes [2-6]. The establishment of such domains
typically involves positive feedback loops based on reaction-diffusion and/or
actin-mediated vesicle transport [3, 7, 8]. How these elements may adapt polarity
domain size to cellular geometry is not known. Here, by tracking the width of
successive oscillating Cdc42-GTP domains in fission yeast spores [9], we find
that domain width scales with local cell-surface radii of curvature over an 8
fold range, independently of absolute cell volume, surface, or Cdc42-GTP
concentration. This local scaling requires formin-nucleated cortical actin cables
and the fusion of secretory vesicles transported along these cables with the
membrane. These data suggest that reaction-diffusion may set a minimal domain
size and that secretory vesicle transport along actin cables may dilute and
extend polarity domains to adapt their size to local cell-surface curvature. This
work reveals that actin networks may act as micrometric curvature sensors and
uncovers a generic morphogenetic principle for how polarity domains define their
size according to cell morphologies.
PMID- 26441354
TI - The Nuclear Proteome of a Vertebrate.
AB - The composition of the nucleoplasm determines the behavior of key processes such
as transcription, yet there is still no reliable and quantitative resource of
nuclear proteins. Furthermore, it is still unclear how the distinct nuclear and
cytoplasmic compositions are maintained. To describe the nuclear proteome
quantitatively, we isolated the large nuclei of frog oocytes via microdissection
and measured the nucleocytoplasmic partitioning of ~9,000 proteins by mass
spectrometry. Most proteins localize entirely to either nucleus or cytoplasm;
only ~17% partition equally. A protein's native size in a complex, but not
polypeptide molecular weight, is predictive of localization: partitioned proteins
exhibit native sizes larger than ~100 kDa, whereas natively smaller proteins are
equidistributed. To evaluate the role of nuclear export in maintaining
localization, we inhibited Exportin 1. This resulted in the expected re
localization of proteins toward the nucleus, but only 3% of the proteome was
affected. Thus, complex assembly and passive retention, rather than continuous
active transport, is the dominant mechanism for the maintenance of nuclear and
cytoplasmic proteomes.
PMID- 26441356
TI - Contextual Feedback to Superficial Layers of V1.
AB - Neuronal cortical circuitry comprises feedforward, lateral, and feedback
projections, each of which terminates in distinct cortical layers [1-3]. In
sensory systems, feedforward processing transmits signals from the external world
into the cortex, whereas feedback pathways signal the brain's inference of the
world [4-11]. However, the integration of feedforward, lateral, and feedback
inputs within each cortical area impedes the investigation of feedback, and to
date, no technique has isolated the feedback of visual scene information in
distinct layers of healthy human cortex. We masked feedforward input to a region
of V1 cortex and studied the remaining internal processing. Using high-resolution
functional brain imaging (0.8 mm(3)) and multivoxel pattern information
techniques, we demonstrate that during normal visual stimulation scene
information peaks in mid-layers. Conversely, we found that contextual feedback
information peaks in outer, superficial layers. Further, we found that shifting
the position of the visual scene surrounding the mask parametrically modulates
feedback in superficial layers of V1. Our results reveal the layered cortical
organization of external versus internal visual processing streams during
perception in healthy human subjects. We provide empirical support for
theoretical feedback models such as predictive coding [10, 12] and coherent
infomax [13] and reveal the potential of high-resolution fMRI to access internal
processing in sub-millimeter human cortex.
PMID- 26441357
TI - Oral azithromycin as the systemic treatment of choice in the treatment of
meibomian gland disease.
PMID- 26441358
TI - Sex in Nursing Homes: A Survey of Nursing Home Policies Governing Resident Sexual
Activity.
AB - OBJECTIVE: To identify nursing home (NH) standards related to sexual activity and
sexual relationships for residents through a nationwide survey of directors of
nursing (DONs). METHODS: A national survey was distributed online and was
completed by 366 DONs of skilled nursing facilities. The DONs answered questions
concerning policies and experiences related to sexual activities of their
residents including types of resident sexual activity they have encountered,
perceptions about residents with dementia engaging in sexual activity, and
policies pertaining to sexual activity including masturbation. RESULTS: The
results of the survey demonstrated that the vast majority (71.2%) indicated that
there had been issues regarding residents' sexual activities in their facilities
with over one-half (58%) of the DONs reporting situations of resident with
resident sexual activity and 60% with situations of resident masturbation. More
than one-half (56.6%) require a family or designated representative to approve
sexual activity for a cognitively impaired resident. For a cognitively intact
resident, 12.4% of facilities still require family or designated representative
to approve sexual activity. However, despite the prevalence of sexual activity,
the majority of NHs (63.4%) actually do not have policies dealing with resident
sexual activity. Of the NHs with policies, 58.6% have written policies in place,
with 11.2% requiring a physician order to allow sexual activity and 9.5%
requiring a physician order to restrict sexual activity. CONCLUSIONS: Issues
related to sexual activity in NH residents are quite prevalent, however, the
rates of policies related to sexual activity are low and the policies and
restrictions are not uniform. Our study suggests nursing homes should have a
clear policy addressing resident sexual activity. It would be beneficial for such
a policy to be communicated to residents and their families as part of an
admission package instead of waiting for sexual interest to be noticed. This
would enable residents to engage in sexual activity with understanding and
support rather than hiding.
PMID- 26441361
TI - Error in the Article by Kavanaugh et al (Arthritis Care Res (Hoboken), March
2015).
PMID- 26441362
TI - N400-like responses to three-chord harmonic sequences with unexpected out of key
endings: scalp topography, cortical sources, and perspectives for a clinical use.
AB - A series of ERP components, each provided with both a precise timing with respect
to stimulation and a specific cortical localization, reflects the temporal
succession of processing stages of music information. This makes the musical
stimulus potentially usable to probe residual brain functions in non
communicating patients with disorders of consciousness. In an attempt to find a
simple stimulation protocol that was suitable for use in a clinical setting, the
purpose of this study was to verify whether a minimum-length musical stimulus,
provided with a definite music-syntactic connotation, was still able to elicit
musical ERPs in a group of eight healthy subjects. The stimulus was composed of
the minimum number of chords necessary and sufficient to enable the subject to
predict a plausible closure of the sequence (priming) and, at the same time, to
provide him/her with the closing chord of the sequence (target), either congruous
(probable closing) or not (improbable closing) to the tonal context. The
subject's task was to discriminate and recognize the irregular targets. The
components that were expected to be elicited, in this experimental situation,
were ERAN, N5, P600/LPC. Conversely, in addition to these former components, we
unexpectedly observed a N400-like component. To determine whether this component
was a real N400, we submitted our data to a sLORETA analysis in order to identify
its cortical generators. Irregular chords showed higher current densities with
respect to regular ones on the right-sided medial and superior temporal gyri,
superior and inferior parietal lobules, fusiform and parahippocampal gyri, and on
the bilateral posterior cingulate cortex. In particular, the N400-like wave seems
to share with the word-primed music-elicited N400 certain generators that are
located in cortical areas BA 21/37 and BA 22. This suggests that even chord
primed chord targets can convey extra-musical meanings and that, consequently,
they might be useful in assessing residual higher-order information-processing
capabilities in non-communicating patients with disorders of consciousness.
PMID- 26441359
TI - Advanced Age and Medication Prescription: More Years, Less Medications? A
Nationwide Report From the Italian Medicines Agency.
AB - BACKGROUND: In older adults co-occurrence of multiple diseases often leads to use
of multiple medications (polypharmacy). The aim of the present study is to
describe how prescription of medications varies across age groups, with specific
focus on the oldest old. METHODS: We performed a cross-sectional study using 2013
data from the OsMed Health-DB database (mean number of medicines and defined
daily doses prescribed in 15,931,642 individuals). There were 3,378,725
individuals age 65 years or older (21.2% of the study sample). RESULTS: The mean
number of prescribed medications progressively rose from 1.9 in the age group <65
years to 7.4 in the age group 80-84 years and then declined, with a more marked
reduction in the age group 95 years or older with a mean number of 2.8
medications. A similar pattern was observed for the mean number of defined daily
doses. Among participants age >=65 years, proton pump inhibitors were the most
commonly prescribed medication (40.9% of individuals >=65 years), followed by
platelet aggregation inhibitors (32.8%) and hydroxy-methylglutaryl-coenzyme A
reductase inhibitors (26.1%). A decline in prescription was observed among
individuals age 90 years or older, but this reduction was less consistent for
medications used to treat acute conditions (ie, antibiotics and glucocorticoids)
rather than preventive medicines commonly used to treat chronic diseases (ie,
antihypertensive medications and hydroxy-methylglutaryl-coenzyme A reductase
inhibitors). CONCLUSIONS: The burden of medication treatment progressively
increases till age 85 and substantially declines after age of 90 years. Patterns
of medication prescription widely vary across age groups.
PMID- 26441363
TI - Cognitive processess and cognitive reserve in multiple sclerosis.
AB - Multiple Sclerosis (MS) is characterized by motor, cognitive, and
neuropsychiatric symptoms, which can occur independently. While MS is
traditionally considered an inflammatory disease of the white matter,
degeneration of gray matter is increasingly recognized as an important
contributor to the progressive cognitive decline. A protective factor against the
progression of cognitive dysfunction in MS could be the cognitive reserve,
defined as resistance to brain dysfunction. Aim of the present study is to
evaluate the role of cognitive reserve for different aspects of cognitive
dysfunction of patients with MS. We found that patients with MS and lower
cognitive reserve have poorer neuropsychological performance and slower
information speed processing. These findings support the notion that intellectual
reserve may protect some aspects of cognitive function in patients with MS.
PMID- 26441364
TI - Failure in evoking the trigeminal cardiac reflex by mandibular stretching in
healthy volunteers.
AB - Stimulation of trigeminal sensory afferences has been reported to evoke
hypotension and bradycardia, a phenomenon known as the trigeminal cardiac reflex.
We attempted to evoke such a reflex through cycles of alternate mandibular
stretching in healthy volunteers, as previously reported, for its possible
therapeutic exploitation. In Phase 1 of the study, 10 healthy volunteers [5 male,
5 female, age (mean +/- SD) 27+/-2 years)] underwent 2 randomized sessions of
automated monitoring, every 6 minutes, of systolic blood pressure (SBP),
diastolic (D) BP, and heart rate (HR), with a one-week interval, either with
mandibular stretching (12 minutes with a spring device fitted in the mouth), or
nothing (control). Observation was prolonged for 180 minute after the end of the
stretching. In Phase 2, 7 other volunteers (4 male and 3 female, age 24+/-1.3
years) repeated the protocol with a sampling interval of 2 minutes until the end
of stretching. Baseline levels of SBP, DBP and HR were similar in the test and
control sessions. There was a progressive fall of BP and HR as a function of time
during the test session. With stretching: SBP changed from 119.2+/-10.1 to
118.1+/-10.1 to 115.8+/-10.5 mmHg, at baseline, end of stretching and 180 minutes
after, respectively, p<0.001 at ANOVA for time effect). However, similar changes
occurred in the control group: from 120.7+/-12.0 to 120.8+/-12.0 to 115.4+/-3.6
mmHg at the same times, P=0.822 for group effect). In Phase 2, again we observed
no significant changes for any of the parameters investigated as a function of
treatment. Despite attempts at maximum standardization of study condition and the
use of operator-independent BP and HR measurements, we could not detect
significant BP or HR effects of repeated mandibular stretching.
PMID- 26441365
TI - Hypnotizability and the position sense: proprioceptive localization of the hand.
AB - We investigated whether healthy subjects with high (highs) and low (lows)
hypnotizability scores differ in the ability to report the position of their
right hand in the horizontal plane at the end of passive and active arm movements
directed to lateral, intermediate and medial targets of the right hemispace under
correct or incorrect visual feedback. Results showed that incorrect visual
feedback increased the error in both groups. In lows, the error was similar after
active and passive movements; in highs, it was lower for active than passive
movements toward the medial position, but lower for passive than for active
movements for the lateral one. The highs' error was significantly lower than the
lows' one only for the active movements directed toward the medial hand position.
Hypnotizability-related differences may be due to different role of efferent
copies in highs and lows.
PMID- 26441366
TI - Effects of combined ferrous sulfate administration and exposure to static
magnetic field on brain oxidative stress and emotional behavior.
AB - The present study was done to investigate behavioral effects and oxidative stress
in iron- treated and co-exposed static magnetic field (SMF)-iron rats. Anxiety in
the elevated plus- maze test, and motor skills were also assessed in the
stationary beam and suspended string tests. After behavioral tests, the rats were
anesthetized and their brains were removed for biochemical analysis. The co
exposure to iron and SMF induced a significant difference in elevated plus-maze
test in rats. The frequency of entries and time spent in the open arms was
significantly reduced (p<0.05) in the iron- and SMF-exposed group compared with
the group treated with iron alone and in the control group. However, no
significant difference was noticed for the motor skill test between the three
groups. The biochemical investigation showed that malondialdehyde level increased
(p<0.001) and that glutathione level and catalase enzyme activity decreased
(p<0.001) in brain of iron- and SMF-exposed group. The dose of iron alone used in
present study, was unable to induce any effect. However, the 128 mT SMF in the
presence of iron ions in the body can induce disruption in the emotional behavior
and can produce oxidative stress in brain tissue of rats.
PMID- 26441367
TI - Cystadenocarcinoma of the salivary glands with potential lymph node metastasis.
AB - Cystadenocarcinoma derived from the salivary gland in the head and neck region is
an extremely rare malignancy. Therefore, the clinicopathological characteristics
is not well understood. The purpose of this study was to clarify the
clinicopathological characteristics, and present a total of four patients who
were treated at the National Cancer Center Hospital East during the period
between 1995 and 2012. The patients were all male, with ages ranging from 47 to
74 years old. The primary sites were the parotid glands, submandibular gland and
minor salivary gland of the tongue. Within the follow-up period from 19 to 54
months, lymph node metastases were observed in three of the four patients.
However, all the patients were salvaged by additional resection, including neck
dissection, and remain alive to date without distant metastases.
Cystadenocarcinoma is classified as a low-grade histological subtype of salivary
gland tumors. Although the tumor has the potential to produce lymph node
metastases, as shown in our patients, it is generally an indolent tumor with a
good prognosis as compared with high-grade subtypes. This study suggests that a
long-term follow up paying close attention to lymph node metastases is necessary
for cystadenocarcinoma.
PMID- 26441368
TI - Predictive factors and pattern of central lymph node metastasis in unilateral
papillary thyroid carcinoma.
AB - OBJECTIVE: Prophylactic central neck dissection (CND) for papillary thyroid
carcinoma (PTC) remains controversial. The aim of this study was to evaluate the
patterns and predictive factors of central lymph node metastasis in cases of PTC
that were clinically determined to be node negative. METHODS: We studied 485
patients who have unilateral PTC without clinical lymph node metastasis and
underwent total thyroidectomy and prophylactic bilateral CND from 2003 to 2012,
retrospectively. The frequency, subsite and predictive factors of central lymph
node metastasis were analyzed. RESULTS: In total, 166 (32.4%) patients had occult
central lymph node metastases. The most common subsite of central node metastases
was the ipsilateral paratracheal lymph node (26.0%), followed by pretracheal
(12.5%), prelaryngeal (5.0%), and contralateral paratracheal (3.9%) lymph nodes.
The tumor size larger than 0.5cm (p=0.003), age under 45 (p<0.001) and
extrathyroidal extension (p=0.028) were associated with ipsilateral central
compartment metastasis in multivariate analysis. Contralateral central node
metastasis was associated with tumor size >3cm, age under 45, and multifocality
and ipsilateral central node metastasis in univariate analysis, but it was
associated with only ipsilateral central node metastasis in multivariate analysis
(p=0.001). CONCLUSION: Prophylactic CND might be considered for PTC patients with
large tumor size or extrathyroidal extension based on rates of lymph node
metastasis. Unilateral CND might be appropriate as prophylactic CND due to the
low metastatic rate to the contralateral paratracheal node.
PMID- 26441369
TI - Posttraumatic olfactory dysfunction.
AB - Impairment of smell may occur following injury to any portion of the olfactory
tract, from nasal cavity to brain. A thorough understanding of the anatomy and
pathophysiology combined with comprehensively obtained history, physical exam,
olfactory testing, and neuroimaging may help to identify the mechanism of
dysfunction and suggest possible treatments. Although most olfactory deficits are
neuronal mediated and therefore currently unable to be corrected, promising
technology may provide novel treatment options for those most affected. Until
that day, patient counseling with compensatory strategies and reassurance is
essential for the maintenance of safety and QoL in this unique and challenging
patient population.
PMID- 26441370
TI - Past, present and future of macrolide therapy for chronic rhinosinusitis in
Japan.
AB - In 1984, the effectiveness of low-dose, long-term erythromycin treatment
(macrolide therapy) for diffuse panbronchiolitis (DPB) was first reported in
Japan. The 5-year survival rate for DPB improved from 62.9 to 91.4% after
implementation of macrolide therapy. The usefulness of this treatment has since
been demonstrated in patients with other chronic airway diseases, such as chronic
bronchitis, cystic fibrosis, bronchiectasis, bronchial asthma, and chronic
rhinosinusitis (CRS). The new 14-membered macrolides clarithromycin and
roxithromycin and the 15-membered macrolide azithromycin are also effective for
treating these inflammatory diseases. The mechanism of action of the 14- and 15
membered macrolides may involve anti-inflammatory rather than anti-bacterial
activities. Macrolide therapy is now widely used for the treatment of CRS in
Japan; it is particularly effective for treating neutrophil-associated CRS and is
useful for suppressing mucus hypersecretion. However, macrolide therapy is not
effective for eosinophil-predominant CRS, which is characterized by serum and
tissue eosinophilia, high serum IgE levels, multiple polyposis, and bronchial
asthma. Recent reports have described the clinical efficacy of macrolides in
treating other inflammatory diseases and new biological activities (e.g., anti
viral). New macrolide derivatives exhibiting anti-inflammatory but not anti
bacterial activity thus have therapeutic potential as immunomodulatory drugs. The
history, current state, and future perspectives of macrolide therapy for treating
CRS in Japan will be discussed in this review.
PMID- 26441371
TI - Synthesis of Well-Defined Oligo(2,5-dialkoxy-1,4-phenylene vinylene)s with Chiral
End Groups: Unique Helical Aggregations Induced by the Chiral Chain Ends.
AB - Oligo(2,5-dialkoxy-1,4-phenylenevinylene)s containing three different chiral
alkoxy substituents on the phenyl end groups with structurally regular (all
trans) controlled repeat units have been prepared; these compounds showed highly
enhanced aggregation-induced circular dichroism (AICD; formation of
supramolecular polymers), and an inversion of the CD signal was observed even
with the same end groups under certain conditions.
PMID- 26441372
TI - Chiral Pool-Based Synthesis of Naphtho-Fused Isocoumarins.
AB - A variety of chiral derivatives of benzo[d]naphtho[1,2-b]pyran-6-one were
prepared in a single step by Et3 N-mediated condensation of homophthalic
anhydride with different derivatives of (S)-amino acid chlorides at -5 degrees C
by employing a chiral pool methodology.
PMID- 26441373
TI - A systematic review of the neurophysiology of mindfulness on EEG oscillations.
AB - Mindfulness meditation has been purported to be a beneficial practice for
wellbeing. It would therefore be expected that the neurophysiology of mindfulness
would reflect this impact on wellbeing. However, investigations of the effects of
mindfulness have generated mixed reports of increases, decreases, as well as no
differences in EEG oscillations in comparison with a resting state and a variety
of tasks. We have performed a systematic review of EEG studies of mindfulness
meditation in order to determine any common effects and to identify factors which
may impact on the effects. Databases were reviewed from 1966 to August 2015.
Eligibility criteria included empirical quantitative analyses of mindfulness
meditation practice and EEG measurements acquired in relation to practice. A
total of 56 papers met the eligibility criteria and were included in the
systematic review, consisting of a total 1715 subjects: 1358 healthy individuals
and 357 individuals with psychiatric diagnoses. Studies were principally examined
for power outcomes in each bandwidth, in particular the power differentials
between mindfulness and a control state, as well as outcomes relating to
hemispheric asymmetry and event-related potentials. The systematic review
revealed that mindfulness was most commonly associated with enhanced alpha and
theta power as compared to an eyes closed resting state, although such outcomes
were not uniformly reported. No consistent patterns were observed with respect to
beta, delta and gamma bandwidths. In summary, mindfulness is associated with
increased alpha and theta power in both healthy individuals and in patient
groups. This co-presence of elevated alpha and theta may signify a state of
relaxed alertness which is conducive to mental health.
PMID- 26441374
TI - The anatomy of fear learning in the cerebellum: A systematic meta-analysis.
AB - Recent neuro-imaging studies have implicated the cerebellum in several higher
order functions. Its role in human fear conditioning has, however, received
limited attention. The current meta-analysis examines the loci of cerebellar
contributions to fear conditioning in healthy subjects, thus mapping, for the
first time, the neural response to conditioned aversive stimuli onto the
cerebellum. By using the activation likelihood estimation (ALE) technique for
analyses, we identified several distinct regions in the cerebellum that activate
in response to the presentation of the conditioned stimulus: the cerebellar
tonsils, lobules HIV-VI, and the culmen. These regions have separately been
implicated in fear acquisition, consolidation of fear memories and expression of
conditioned fear responses. Their specific role in these processes may be
attributed to the general contribution of cerebellar cortical networks to timing
and prediction. Our meta-analysis highlights the potential role of the cerebellum
in human cognition and emotion in general, and addresses the possibility how
deficits in associative cerebellar learning may play a role in the pathogenesis
of anxiety disorders. Future studies are needed to further clarify the
mechanistic role of the cerebellum in higher order functions and neuropsychiatric
disorders.
PMID- 26441375
TI - Langerhans cells in a dermoid cyst epithelium lining.
PMID- 26441376
TI - Long-term intake of white tea prevents oxidative damage caused by adriamycin in
kidney of rats.
AB - BACKGROUND: White tea infusion (Camelia sinensis) has antioxidants properties.
The infusion contains polyphenols that have been proposed to induce antioxidant
response element (ARE) response via nuclear factor E2-related factor 2 (NRF2).
Adriamycin (ADR) has antitumour properties and oxidative effects. Oxidative
stress is related to a variety of kidney diseases. Prevention of the oxidative
stress through long-term intake of white tea and the study of the molecular
mechanisms involved in protection could be of great interest. Rats were given
distilled water, 0.015 or 0.045 g of solid white tea extract kg(-1) body weight
for 12 months. Animals received an injection of ADR. In kidney, oxidative stress
parameters were measured, the expressions of nuclear factor E2-related factor 2
gene (Nrf2), and detoxifying and antioxidants genes were analysed, and the
activities of catalase (CAT), superoxide dismutase (SOD) and glutathione
reductase (GR) were measured. RESULTS: ADR administration increased oxidative
parameters and decreased the antioxidant activity; significantly increased the
expression of analysed genes and the activity of CAT and SOD and decreased GR
activity. The highest white tea dose protected redox status and inhibited ARE
response. CONCLUSION: Long-term intake of white tea protected kidney against the
oxidative stress. ADR activated the ARE response but in animals treated with the
highest dose of white tea, this response was inhibited, probably for antioxidant
protection. (c) 2015 Society of Chemical Industry.
PMID- 26441377
TI - Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic
neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in
rodent seizure models.
AB - It was reported that antiarrhythmic drugs (AADs) can be useful in controlling
refractory seizures in humans or in enhancing the action of antiepileptic drugs
(AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks
sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2
chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant
activity in a battery of rodent models of epileptic seizures. The compound
displayed a broad spectrum of activity in the 'classical' models as well as in
the models of pharmacoresistant seizures. Furthermore, ADD424042 showed good
therapeutic indices between the anticonvulsant activity and the motor impairment.
On the contrary, no anticonvulsant effects but severe lethality were observed in
the primary anticonvulsant testing of the parent DISO. By performing the whole
cell voltage-clamp experiments in dispersed cortical neurons we demonstrated that
ADD424042 decreased the maximal amplitude of voltage-gated sodium channels with
an IC50 value in nM range. Moreover, the compound enhanced use-dependent block
and decreased excitability in pyramidal neurons in the current-clamp experiments
in cortical slices. Importantly, we found that ADD424042 possessed either no, or
very small cardiotoxic effect. In contrast to DISO, ADD424042 did not produce any
apparent changes in electrocardiogram (ECG) and arterial blood pressure
recordings. ADD424042 had no effect on QT and corrected QT intervals, at a dose
which was 15 times higher than ED50 for the anticonvulsant effect in the MES
model. Taken together, these data suggest that ADD424042 has the potential to
become a lead structure for novel broadly acting AEDs with wide margin of cardiac
safety.
PMID- 26441378
TI - Post-progression survival and progression-free survival in patients with advanced
hepatocellular carcinoma treated by sorafenib.
AB - AIM: Although sorafenib is a standard drug for advanced hepatocellular carcinoma
(HCC), little is known about a patient's clinical course after treatment. We
investigated the effect of post-progression survival (PPS) and progression-free
survival (PFS) on overall survival (OS) in patients whose advanced HCC was
treated by sorafenib. METHODS: We searched in the PubMed database for reports
with survival data of patients with HCC treated with sorafenib monotherapy, and
selected reports with 20 or more patients each that provided data for both OS and
PFS or time to progression (TTP). Median PPS (mPPS) was defined as the period
obtained by subtracting median PFS or TTP (mPFS/TTP) from median OS (mOS). We
identified 56 reports with 5803 patients. We investigated the correlation of mOS
and either mPPS or mPFS/TTP using weighted linear regression. RESULTS: Median PPS
correlated with mOS (r = 0.834) very strongly, whereas mPFS/TTP did not correlate
with mOS as highly as PPS did (r = 0.546). When we stratified survival data by
Child-Pugh classification, a significantly greater average percentage of mPPS to
mOS was seen in Child-Pugh class A (54.4 +/- 17.6%) than in Child-Pugh class B
(32.0 +/- 11.6%) (P = 0.015). CONCLUSION: PPS highly correlated with OS, and its
importance should be more emphasized for advanced HCC patients treated after
sorafenib therapy, whereas we need to take more care in interpreting the results
of PFS to evaluate treatment efficacy in clinical trials of advanced HCC.
PMID- 26441379
TI - Hydrophilic Molecularly Imprinted Resorcinol-Formaldehyde-Melamine Resin Prepared
in Water with Excellent Molecular Recognition in Aqueous Matrices.
AB - Hydrophilic molecularly imprinted resorcinol-formaldehyde-melamine resin (MIRFM)
is synthesized in water and shows excellent molecular recognition in aqueous
matrices. The double functional monomers resorcinol and melamine, and the cross
linker formaldehyde, are all hydrophilic, and then the hydrophilic groups (such
as hydroxyls, imino groups, and ether linkages) can be introduced into MIRFM,
which make the material compatible with aqueous samples. The general principle is
demonstrated by the synthesis of MIRFM using sulfanilamide as a dummy template
for the selective recognition to sulfonamides (SAs) in milk samples. Resorcinol
and melamine can interact with the template mainly by hydrogen bonding and pi-pi
interaction, which makes MIRFM and the analytes have strong affinity. Besides,
melamine can improve the rigidity of MIRFM and accelerate the polymerization
process, so there is no need to add base or acid as a catalyst, which guarantees
the success of molecular imprinting. MIRFM shows higher recovery and improved
purification effect for SAs, in comparison to silica, HLB, C18, and SCX. Because
of its excellent hydrophilicity and specificity, MIRFM is promising to be applied
in biological, environmental, and clinical fields.
PMID- 26441380
TI - Can Abdominal Hypopressive Technique Change Levator Hiatus Area?: A 3-Dimensional
Ultrasound Study.
AB - This study aimed to evaluate the levator hiatus area (LHA) at rest and during the
performance of maximal pelvic floor muscle (PFM) contractions, during the
abdominal hypopressive technique (AHT), and during the combination of PFM
contractions (PFMCs) and the AHT. The study included 17 healthy nulliparous women
who had no history of pelvic floor disorders. The LHA was evaluated with the
patients in the lithotomy position. After a physiotherapist instructed the
patients on the proper performance of the PFM and AHT exercises, 1 gynecologist
performed the 3-dimensional translabial ultrasound examinations. The LHA was
measured with the patients at rest. The PFMC alone, the AHT alone or the AHT in
combination with a PFMC with 30 seconds of rest between the evaluations were
performed. Each measurement was performed 2 times, and the mean value was used
for statistical analysis. The Wilcoxon test was used to test the differences
between the 2 maneuvers. Similar values were observed when comparing the LHA of
the PFM at rest (12.2 +/- 2.4) cm and during the AHT (11.7 +/- 2.6) cm (P =
0.227). The AHT+ PFMC (10.2 +/- 1.9) cm demonstrated lower values compared with
AHT alone (11.7 +/- 2.6) cm (P = 0.002). When comparing the PFMC (10.4 +/- 2.1)
cm with the AHT + PFMC (10.2 +/- 1.9) cm, no significant difference (P = 0.551)
was observed. During PFMC, the constriction was 1.8 cm; during the AHT, the
constriction was 0.5 cm; and during the AHT + PFMC, it was 2 cm. The LHA assessed
by 3-dimensional ultrasound did not significantly change with AHT. These results
support the theory that AHT does not strengthen PFM.
PMID- 26441381
TI - Thyroid Nodule Doubling Time is Not a Reliable Indicator of Benign or Malignant
Nature.
AB - Thyroid nodules are often followed up with serial ultrasound imaging. Doubling
time is well established in the evaluation of lung nodules. We examined whether
benign and malignant thyroid nodules exhibit differences in doubling time.This
retrospective, IRB-approved study included patients with nodules aspirated
between January and June 2012 (benign), and January 2012 to December 2014
(suspicious or malignant), no interval thyroidectomy, and two ultrasound
examinations longer than 180 days apart. Diameters and morphology were assessed
by a single observer, demographics recorded, and doubling time calculated. Area
under the receiver operating characteristic curve was derived. Society of
Radiologists in Ultrasound criteria were used to determine aspiration
appropriateness initially and after follow-up.59 patients with 61 nodules were
included. Statistically significant between-group differences exist for sex,
solidity, echogenicity, and microcalcifications, with no significant differences
in doubling time, age, days between studies, vascularity, or mean diameter.
Benign nodules' doubling time was 340 to 7134 days (mean, 2196; median, 1593),
with 9 nodules that decreased in size. Malignant nodules' doubling time was 451
to 17182 days (mean, 3940; median, 2137), with 7 nodules that decreased in size.
Using a threshold of 1100 days, sensitivity and specificity of doubling time to
predict malignancy are 19.0% and 86.7%, respectively. Area under the receiver
operating characteristic curve is 0.39. Follow-up imaging resulted in 6
additional benign and 0 additional malignant nodules meeting criteria.There is no
significant difference in benign or malignant nodules' doubling times, and a
decrease in nodule size is nonspecific. These findings challenge the underlying
rationale for routine imaging follow-up of thyroid nodules.
PMID- 26441382
TI - Risks of Being Malignant or High Risk and Their Characteristics in Breast Lesions
20 mm or Larger After Benign Results on Ultrasonography-Guided 14-Gauge Core
Needle Biopsy.
AB - PURPOSE: The malignancy risk, risk of being high-risk lesions after benign
results on ultrasonography-guided 14-gauge core needle biopsies (US-CNBs), and
their characteristics in breast lesions of 20 mm or greater were investigated.
METHODS: Eight hundred forty-seven breast lesions with benign results on US-CNB
were classified as benign, high risk, and malignant through excision and clinical
follow-up. The risks of being malignant or high risk were analyzed in all
lesions, lesions 20 to 29 mm, and lesions 30 mm or greater. Their
clinicopathological characteristics were evaluated. RESULTS: Of 847, 18 (2.1%)
were malignant, 53 (6.3%) were high-risk lesions, and 776 (91.6%) were benign. Of
18 malignancies, 6 (33.3%) were malignant phyllodes tumors and 12 (66.7%) were
carcinomas. In benign lesions 20 to 29 mm, risks of being malignant or high risk
were 1.6% (9 of 566) and 4.4% (25 of 566). In 281 lesions 30 mm or greater, the
risks of being malignant or high risk were 3.2% and 10%. The risk of being high
risk in lesions 30 mm or greater was 10%, significantly higher than 4.4% of
lesions 20 to 29 mm (P = 0.002). CONCLUSIONS: Excision can be considered in
lesions measuring 20 mm or larger because of the 2.1% malignancy risk and the
6.3% risk of being high-risk lesions despite benign results on US-CNB. Excision
should be considered in lesions measuring 30 mm or larger because of the 3.2%
malignancy risk and the 10% risk of being high-risk lesions.
PMID- 26441383
TI - Novel genetic capacitors and potentiators for the natural genetic variation of
sensory bristles and their trait specificity in Drosophila melanogaster.
AB - Cryptic genetic variation (CGV) is defined as the genetic variation that has
little effect on phenotypic variation under a normal condition, but contributes
to heritable variation under environmental or genetic perturbations. Genetic
buffering systems that suppress the expression of CGV and store it in a
population are called genetic capacitors, and the opposite systems are called
genetic potentiators. One of the best-known candidates for a genetic capacitor
and potentiator is the molecular chaperone protein, HSP90, and one of its
characteristics is that it affects the genetic variation in various morphological
traits. However, it remains unclear whether the wide-ranging effects of HSP90 on
a broad range of traits are a general feature of genetic capacitors and
potentiators. In the current study, I searched for novel genetic capacitors and
potentiators for quantitative bristle traits of Drosophila melanogaster and then
investigated the trait specificity of their genetic buffering effect. Three
bristle traits of D. melanogaster were used as the target traits, and the genomic
regions with genetic buffering effects were screened using the 61 genomic
deficiencies examined previously for genetic buffering effects in wing shape. As
a result, four and six deficiencies with significant effects on increasing and
decreasing the broad-sense heritability of the bristle traits were identified,
respectively. Of the 18 deficiencies with significant effects detected in the
current study and/or by the previous study, 14 showed trait-specific effects, and
four affected the genetic buffering of both bristle traits and wing shape. This
suggests that most genetic capacitors and potentiators exert trait-specific
effects, but that general capacitors and potentiators with effects on multiple
traits also exist.
PMID- 26441384
TI - Formulation and stabilization of nano-/microdispersion systems using naturally
occurring edible polyelectrolytes by electrostatic deposition and complexation.
AB - This review paper presents an overview of the formulation and functionalization
of nano-/microdispersion systems composed of edible materials. We first
summarized general aspects on the stability of colloidal systems and the roles of
natural polyelectrolytes such as proteins and ionic polysaccharides for the
formation and stabilization of colloidal systems. Then we introduced our research
topics on (1) stabilization of emulsions by the electrostatic deposition using
natural polyelectrolytes and (2) formulation of stable nanodispersion systems by
complexation of natural polyelectrolytes. In both cases, the preparation
procedures were relatively simple, without high energy input or harmful chemical
addition. The properties of the nano-/microdispersion systems, such as particle
size, surface charge and dispersion stability were significantly affected by the
concerned materials and preparation conditions, including the type and
concentration of used natural polyelectrolytes. These dispersion systems would be
useful for developing novel foods having high functionality and good stability.
PMID- 26441385
TI - Electrical Instability Induced by Electron Trapping in Low-Bandgap Donor-Acceptor
Polymer Field-Effect Transistors.
AB - The mechanism of electrical instability and the double slope of p-type organic
field-effect transistors (OFETs) fabricated from low-bandgap donor-acceptor
copolymers are resolved. Those polymers enable electron conduction in the device,
which leads to electron trapping and consequent formation of -SiO(-). This causes
a turn-on voltage shift, hole-mobility increase, and double-slope occurrence.
These findings tremendously impact the molecular design and device engineering of
OFETs.
PMID- 26441386
TI - Human bocaviruses: Possible etiologic role in respiratory infection.
AB - Four species of human bocaviruses (HBoV) are currently included in the Bocavirus
genus. There is satisfactory evidence demonstrating an association between HBoV1
and respiratory disease in children, and there is evidence that HBoV2 (and
possibly the HBoV3 and HBoV4 species) are associated with gastroenteritis. In
particular, HBoV1 has been associated with a prolonged period of persistence in
the mucosa of the respiratory tract. Virus persistence does play a role in the
high frequency of co-infections with proper pathogens of the upper and lower
respiratory tracts. The high detection rate of multiple respiratory viruses in up
to 83% of respiratory specimens and the presence of asymptomatic HBoV1 infections
complicate the elucidation of the pathogenic role of the agent. Overall, a large
amount of data are available concerning HBoV1, whereas little information is
available about other bocavirus species. High viral loads are often associated
with symptoms, and viremia may be associated with systemic manifestations such as
encephalopathy. The effects and mechanisms of latency, persistence, reactivation,
and reinfection are poorly understood. Thus, particularly in co-infections, the
pathogenic contribution of the detected bocavirus species cannot be accurately
stated. This review summarizes the current knowledge of HBoV species and provides
perspectives for future clinical studies.
PMID- 26441387
TI - Nationwide shift from microscopic to endoscopic transsphenoidal pituitary
surgery.
AB - PURPOSE: Transsphenoidal pituitary surgery can be carried out with either an
operating microscope or with an endoscope, but the relative frequency of both
techniques is unknown. METHODS: All microscopic and endoscopic transsphenoidal
pituitary surgeries were extracted from the Centers for Medicare and Medicaid
Services Part B data files between the years 2003 and 2013. National and state
level trends were compared over time. RESULTS: Endoscopic surgery significantly
increased and microscopic surgery significantly decreased over the years 2003
2013. Thirty-eight of 48 states increased their use of endoscopic surgery, while
38 of 48 states decreased their use of microscopic surgery. CONCLUSIONS:
Nationwide data show a clear trend for an increasing use of endoscopic
transsphenoidal surgery at the expense of microscopic surgery. The underlying
causes of these trends are unknown, but clearly deserve further investigation.
PMID- 26441388
TI - Risk model for suspected acute coronary syndrome is of limited value in an
emergency department.
AB - INTRODUCTION: Among patients with acute chest pain, acute coronary syndrome (ACS)
is seen only in a minority of the patients, which raises the question, whether it
is possible to separate a group with a high risk of ACS for admission to a
cardiac care unit (CCU) from those with a low risk who would be treated at an
emergency department (ED). The aim of this study was to describe a risk
stratification model for a Danish context. METHODS: This was a historic
prospective cohort study of patients with suspicion of ACS. The patient was
defined as a low-risk patient and admitted to the ED if: 1) electrocardiogram
(ECG) was normal, 2) the patient did not have persisting chest pain and 3) there
was no history of ischaemic heart disease, heart failure or cardioverter
defibrillator. Otherwise, patients were admitted to the CCU. The primary outcome
was whether the ACS diagnosis was confirmed or rejected. RESULTS: We included a
total of 488 patients with suspicion of ACS, 50% of whom were low-risk patients.
17% had a verified ACS; 10% of those in the low-risk group and 24% of those in
the high-risk group (p = 0.0001). Among the verified ACS cases, 71% went
primarily to the CCU. The odds ratio for an ACS if assigned to the high-risk
group was 3.0. Allocation to the high-risk group, male gender and age above 60
years was associated with a higher risk of ACS. For patients fulfilling the high
risk definition, sensitivity was 71%, specificity 55%, negative predictive value
90% and positive predictive value 24% for an ACS. CONCLUSIONS: The model for
stratification separated patients into two equal groups, allocated 71% of all ACS
directly to the CCU and could not be improved by any of the additional factors
examined. Further development of referral strategies for chest pain patients is
required. FUNDING: none. TRIAL REGISTRATION: not relevant.
PMID- 26441389
TI - Exploring challenges and solutions in the preparation of surgical patients.
AB - INTRODUCTION: Handover of surgical patients from ward to operating room is a
sensible point for information and communication failures. Guidelines were
developed for preparation of surgical patients. Our aim was to explore if
patients are sufficiently prepared for surgery according to local guidelines and
to identify challenges and solutions for correct preparation through interactive
table simulation-based workshops involving the various professions and
specialties. METHODS: Firstly, specific tasks in the hospital guidelines were
monitored for all surgical procedures during one week. Secondly, workshops
including table simulations involving the various professions and specialties
were held. RESULTS: In total, 314 surgical procedures were performed of which 196
were eligible for analysis. Emergency procedures showed the poorest results with
non-completed tasks comprising 58% of electronic patient management system tasks,
26% of anaesthesia record tasks, 24% of medication tasks, 14% of blood test tasks
and 12% of patient record tasks. In two workshops held for each of four
specialties, a total of 21 participants mapped the preoperative patient journey
with related responsibilities, tasks and written documentation. Furthermore,
challenges and suggestions for solutions were identified. CONCLUSIONS: Completion
of mandatory tasks for surgical patient preparation was poor. Workshops with
table simulations actively involved the stakeholders from various professions and
specialties in describing the patient trajectory and mandatory tasks according to
hospital guidelines in addition to identifying challenges and solutions for
improvement. FUNDING: none. TRIAL REGISTRATION: not relevant.
PMID- 26441390
TI - Changing presentation of cutaneous malignant melanoma.
AB - INTRODUCTION: The incidence of cutaneous malignant melanoma is rapidly increasing
in Denmark like in other Northern and Western European countries. Our objective
was to investigate the characteristics of current patients suffering from
cutaneous malignant melanoma. METHODS: We evaluated patient and tumour
characteristics in a cross-sectional study based on data from the Danish Melanoma
Register. We included all patients diagnosed with cutaneous malignant melanoma in
Healthcare Region Zealand in 2012 and 2013. RESULTS: We identified 520 patients
with invasive cutaneous malignant melanoma. More females than males suffered from
cutaneous malignant melanoma. Furthermore, females were younger than males, and
the anatomical distribution of malignant melanoma varied between the genders.
Outcome of sentinel lymph node biopsy was associated with tumour thickness.
CONCLUSIONS: When comparing findings in our study with earlier Danish studies, we
see a trend towards an increase in age at diagnosis. Furthermore, tumour
thickness is decreasing and the topical distribution of cutaneous malignant
melanoma in females changes towards a male pattern. FUNDING: none. TRIAL
REGISTRATION: The study has been approved by the Danish National Data Protection
Agency.
PMID- 26441391
TI - Changes in antimicrobial susceptibility patterns of Klebsiella pneumoniae,
Escherichia coli and Staphylococcus aureus over the past decade.
AB - INTRODUCTION: Development of antimicrobial resistance is an ongoing and
increasing problem. To provide the best possible treatment for patients it is
crucial that clinicians are aware of the local antimicrobial susceptibility
patterns. The aim of this study was to present an overview of the percentage of
bacterial isolates that are covered by the most commonly used antibiotics in the
area of Copenhagen and to provide clinicians with a practical tool to help chose
the right antimicrobial treatment for their patients. METHODS: We conducted a
study of all bacteria isolates tested for antimicrobial susceptibility at
Hvidovre Hospital, Denmark, from 2004 to 2008. Due to a suspected rise in
resistance in Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae
after this period, updated data for these bacteria are shown for selected
antibiotics until 2014. The department receives samples from hospitals as well as
from primary healthcare. Only one isolate per species per patient per year was
included. RESULTS: A total of 224,033 bacteria isolates were included in this
study. The antimicrobial susceptibility of the various bacteria is presented in a
table. No clinically relevant changes in resistance patterns were noted up to
2014. CONCLUSIONS: A comprehensive and manageable inventory of the resistance
patterns of the major bacteria covering the 2004-2008 period is presented.
Clinicians are encouraged to use the pocket-size table as guidance when choosing
antibiotic treatment. FUNDING: none. TRIAL REGISTRATION: not relevant.
PMID- 26441392
TI - suPAR as a biomarker for risk of readmission and mortality in the acute medical
setting.
AB - INTRODUCTION: The urokinase-type plasminogen activator receptor (uPAR) and its
ligand (suPAR) are involved in numerous physiological and pathological pathways.
Previous studies have shown that an elevated plasma suPAR level is associated
with disease severity and mortality. The aim of this prospective observational
study was to determine if the suPAR level was associated with readmission and
mortality in the acute medical setting. METHODS: Plasma suPAR levels were
measured in 1,036 patients at admission. Follow-up ranged 3-10 months. Cox
proportional hazards model was used to assess the relative contribution of
different risk factors to mortality and readmission. The ANOVA test and Pearson's
chi-squared test were used to compare suPAR tertile level with various variables.
RESULTS: The highest suPAR tertile level was significantly associated with
mortality within 30 days after discharge, with a 6.66 hazard ratio (HR). Similar
associations were found with readmission within the maximum observation period
(HR = 2.26) and within 30 days (HR = 2.08), although the latter became
insignificant when covariates were included. CONCLUSIONS: This study confirms
previous findings of increased mortality and adds the finding that increased long
term readmission rates are associated with elevated suPAR levels. The present
data do, however, not indicate that suPAR may serve as an independent biomarker
for increased risk of short-term readmission in the acute medical setting.
FUNDING: This study was funded by a grant from ViroGates A/S, the company that
produces the suPARnostic assay. TRIAL REGISTRATION: No: H-B-2009-075.
PMID- 26441393
TI - Factors affecting patients' ratings of health-care satisfaction.
AB - INTRODUCTION: Surveys that include rating scales are commonly used to collect
data about patients' experiences. We studied how patients associated their
ratings with their experiences of care. METHODS: A survey and a qualitative study
were conducted at a Danish hospital. Initially, 19 female patients completed a
questionnaire using the response categories from very good to very bad; and
subsequently they participated in a semi-structured interview held within two
days after they completed the questionnaire. Additionally, 44 female patients
participated in an interview within six weeks of completing a questionnaire. A
phenomenological-hermeneutical approach was used in the analysis and
interpretation. RESULTS: Two major themes emerged: experienced versus expected
clinical quality and health-care professional attitude. Patients responded to
each question by combining their experiences of both themes, e.g. a "very good"
experience required that clinical service was provided at the expected level, at
the very least, and that it was provided with recognition and respect.
CONCLUSIONS: The female patients associated their experiences with their ratings,
and two types of relation seemed to be at play: a care relation and a human
relation. This finding can inform health-care practice, but department-specific
examples may be needed to initiate improvements. FUNDING: The study received
funding from the Centre for Patient Experience and Evaluation, Copenhagen,
Denmark. The Danish Scientific Ethical Committees deemed it unnecessary to be
involved in this project. TRIAL REGISTRATION: The Danish Data Protection Agency
number of this study is 2008-58-0035.
PMID- 26441394
TI - Fatal poisoning among patients with drug addiction.
AB - INTRODUCTION: Fatal poisonings among drug addicts in Denmark in 2012 were
examined. Cause of death, abuse pattern and geographic differences are discussed
and data are compared with previous studies. METHODS: All fatal poisonings
examined at the three institutes of forensic medicine in Denmark in 2012 were
included in the study. RESULTS: A total of 188 fatal intoxications were recorded.
The median age increased from 37.5 in 2007 to 41.5 in 2012. The majority were men
(77%). Methadone (59%) was the main intoxicant. The decrease in the frequency of
heroin/morphine deaths since 1997 (71%) continued, declining to 44% in 2002, 33%
in 2007 and finally to 27% in 2012. Few deaths from central stimulants
(amphetamine and cocaine) occurred. Multiple drug use was common and consisted
mainly of opioids, cocaine, amphetamine, cannabis, benzodiazepines and alcohol.
Heroin/morphine use was most frequent on Funen and in South Jutland. Cocaine was
most frequently detected in East Denmark, while amphetamine was more frequent in
West Denmark. CONCLUSIONS: The number of fatal poisonings among drug addicts has
stabilised around 200. The increase in methadone deaths continued and, as in
2007, methadone was the main intoxicant. The increase in methadone deaths seems
to be associated with use of methadone in substitution treatment. Nevertheless,
methadone treatment also seems to save lives, as indicated by the increasing
median age. Use of antidepressants and antipsychotics increased to a high level
compared with 2007, indicating that a considerable number of drug addicts also
have psychiatric illness. FUNDING: none. TRIAL REGISTRATION: not relevant.
PMID- 26441395
TI - Depression is associated with poor prognosis in patients with chronic obstructive
pulmonary disease - a systematic review.
AB - INTRODUCTION: Patients with depression have significantly increased mortality
from somatic disease. The purpose of this article was to review studies that
investigate if there is a prognostic association with depression as co-morbidity
in patients with chronic obstructive pulmonary disease (COPD). We chose the
following outcomes: mortality, suicide behaviour, risk of COPD exacerbation, use
of primary care and prescription data. METHODS: A literature review was performed
on 16 December 2014 in PubMed, Embase, OVID Medline and Cochrane for cohort
studies. Only studies with mortality and exacerbation/hospital admissions were
found. Studies failing to meet relevant criteria in terms of design or/and
outcome, and studies with significant methodological faults were excluded.
RESULTS: A total of 22 cohort studies were included. Of these studies, 20 were
prospective, one retrospective and one was a combined retro- and prospective
study. There was a tendency for studies with more patients and higher
methodological quality to show a positive correlation. Sixteen of the studies
showed that depression was associated with increased mortality (relative risk
(RR): 1.02-3.6) and more COPD exacerbations (RR: 1.3-7.0). CONCLUSIONS: The
results showed that not only is depression a debilitating disease on its own, it
also predisposes to COPD exacerbations and increased mortality in patients with
COPD. Depression in patients with COPD is under-diagnosed and undertreated, and a
stronger focus on the clinical significance of depression as co-morbidity is
warranted.
PMID- 26441396
TI - Neuromuscular blockade for improvement of surgical conditions during laparotomy:
protocol for a randomised study.
AB - INTRODUCTION: During laparotomy, surgeons frequently experience difficult
surgical conditions if the patient's abdominal wall or diaphragm is tense. This
issue is particularly pertinent while closing the fascia and placing the
intestines into the abdominal cavity. Establishment of a deep neuromuscular
blockade (NMB), defined as a post-tetanic-count (PTC) of 0-1, paralyses the
abdominal wall muscles and the diaphragm. We hypothesised that deep NMB (PTC 0-1)
would improve surgical conditions during upper laparotomy as compared to standard
NMB with bolus administration. METHODS: This is an investigator-initiated,
assessor- and patient-blinded, randomised study. A total of 128 patients
scheduled for elective upper laparotomy will be included and randomised to either
continuous deep NMB or standard NMB defined as bolus administrations. Surgical
conditions are evaluated using a five-point rating scale every 30 min. Primary
outcome is the average score for a patient's surgical condition. Secondary
outcomes are, among others, surgical rating score during fascial closure, wound
dehiscence, wound infection requiring surgical drainage and incisional hernia at
the six-month follow-up. CONCLUSIONS: This randomised, double-blinded study
investigates potential effects of deep NMB on surgical conditions and patient
outcomes during elective laparotomy. FUNDING: The study is funded in part by a
research grant from the Investigator Initiated Studies Program of Merck Sharp &
Dohme Corp. TRIAL REGISTRATION: NCT02140593.
PMID- 26441397
TI - The effect of generic switching on concerns about medicine and non-persistence
among Danish adults in a general practice setting.
AB - BACKGROUND: Generic substitution means that one medicinal product is replaced by
another product containing the same active substance. Generic substitution has
existed in Denmark since 1991, and pharmacies are obliged to substitute a generic
version of a medication, unless the general practitioner (GP) has explicitly
stated that it should not be done, or the patient insists on having the more
expensive drug. Generic prescribing, that is prescribing the substance name, is
not allowed in Denmark. Some specialists and patients cast doubt on the real
interchange-ability of generics, although international studies have shown that
most patients have positive attitudes towards generic substitution. The severity
of disease is known to be associated with patients being more concerned about
generic substitution. The generic substitution scheme implies changing from one
drug to another that may vary in brand-name, form, size, colour and taste.
Speculations have been raised as to whether these medication changes between
generic brands or from brand-name drugs to generics or vice versa may cause
patient concerns. Qualitative studies have shown problems in recognising the
substituted medicine and lack of confidence in the identical effect of the
substitutable medicines. Several studies have focused on one specific drug group
such as antihypertensive drugs. However, the influence of generic switching may
affect concerns about medicine differently, depending on drug categories.
Research on generic substitution often focuses on incident drug users, whose
prescription is substituted at their first redemption. Most of these studies did
not identify significant associations between generic substitution and non
adherence, but one study assessing the association between generic substitution
and persistence showed reduced persistence. So far, studies of the effect of
generic drug substitution on drug continuation have not focused on patients'
overall experience of generic switches within one specific drug. AIMS: To analyse
associations between generic substitution and patient characteristics as well as
patients' views on generic medicines, confidence in the healthcare system,
beliefs about medicine, and experience with earlier generic substitution. To
investigate the possible association between a specific generic switch and
patients' concerns about their medicine. To examine how generic switch influences
persistence with long-term treatment with special focus on importance of
patients' concerns and views on generic medicine. METHODS: The design was a
combined cross-sectional questionnaire and register study and additionally a
cohort study. The study was conducted among 6,000 medicine users, who had
redeemed generically substitutable drugs with general reimbursement in September
2008 (2,000 users of antidepressants, 2,000 users of antiepileptics and 2,000
users of other substitutable drugs), who were aged 20 years or older and living
in the Region of Southern Denmark. The medicine users were identified through
Odense PharmacoEpidemiologic Database (OPED). The purpose of the questionnaire
survey was to elucidate patients' experience with medicine, combined with
information from OPED on a single well-defined generic switch of the index drug.
The questionnaire was adapted to the individual subject with reference to their
specific drug (index drug) in every question and index date printed on the
questionnaire. The questionnaire comprises scales from the validated Beliefs
about Medicine Questionnaire (BMQ) and ad hoc constructed scales. By means of
OPED data it was possible to conduct a cohort study comprising information on all
purchased medicine during the 12 months following the index date. The cohort
comprised users of antidepressants and users of antiepileptics. RESULTS: A total
of 2,476 patients (44.1%) were included in the analyses. Experience with earlier
generic switches within the index ATC code was associated with experience of a
generic switch on the index day (OR 5.93; 95% CI 4.70-7.49). However, experience
with earlier generic switches was drug-specific, e.g. having had more than five
earlier switches within other ATC codes reduced the odds of experiencing a
generic switch on the index day. Having negative views on generic medicines also
reduced the odds of experiencing a generic switch on the index day. The second
study showed no statistically significant associations between experiencing a
generic switch on the index day and having more or less concerns about the index
medicine (-0.02 95% CI: -0.10-0.05). Patients experiencing their first-time
switch of a specific drug were at higher risk of non-persistence, hazard ratio
2.98, 95% CI 1.81-4.89, versus those who have never switched, and 35.7% became
non-persistent during the first year of follow-up. Generic switching did not
influence persistence considerably in those having previous experience with
generic switching of the specific drug. CONCLUSION: The overall results from the
thesis showed that experience with earlier generic switches of a specific drug
was associated with making a future generic switch and did not cause additional
concerns about the index medicine. The effect of previous experience with generic
substitution has been shown to be drug-specific. The third study showed that
patients, who are first-time switchers of a specific drug, were at higher risk of
becoming non-persistent compared to never switchers and those having experienced
previous generic switching.
PMID- 26441398
TI - Clinical epidemiological studies of women undergoing surgery for
urogynaecological disorders.
AB - This PhD thesis was performed during my employment at the Center for Clinical
Epidemiology, Odense University Hospital and University of Southern Denmark, 2010
2013. It comprises an overview and four papers, two published in international
peer-reviewed scientific journals, one under review, and one in draft.
INTRODUCTION: Urinary incontinence (UI) and pelvic organ prolapse (POP) are
prevalent disorders among women worldwide, affecting their psychological and
social wellbeing, with reductions in quality of life. Treatment options are
conservative (e.g. pelvic floor exercises, weight loss, and bladder training),
pharmacological, and surgical. Surgery has especially for UI undergone an
improvement during the last decades with development of minimally-invasive sub
urethral sling procedures, and the number of surgeries has increased in Denmark
and other countries. AIMS: In a population of Danish women undergoing surgery for
UI or POP, we aimed: to describe the establishment of the Danish
Urogynaecological Database (DugaBase), and to evaluate the completeness and the
validity of surgery registration in the DugaBase; to study patient reported
outcome measures in Danish women undergoing urogynaecological surgery; to study
the use of symptom-relieving drugs before and after surgery for UI; to study the
use of antibiotics for urinary tract infection (UTI) before and after surgery for
UI METHODS: Study I The completeness of DugaBase was assessed by comparing
procedure codes in the DugaBase to iodes registered in the National Patient
Registry, 2006-2010. The study also included review of medical journals from 200
women (computed randomly from DugaBase), representing 22 departments in Denmark.
Information on selected variables was compared to registered data in the
DugaBase. DATA SOURCES: the National Patient Registry, the DugaBase, and medical
records. Study II was based on a national cohort of women undergoing surgery for
UI and POP registered in the DugaBase, 2006-2011. Clinical data and data from
patient questionnaires were retrieved. DATA SOURCES: the DugaBase. Study III+IV
were cohort studies based on national register data and prescription data. A
total of 2,151 women with a first time surgical procedure for UI within 1996-2010
were included. The data were supplemented with registry information on redeemed
prescriptions on symptom-relieving drugs/antibiotics for UTI/oestrogen,
comorbidity, and educational level and income. DATA SOURCES: the Danish National
Patient Registry, Odense University Pharmacoepidemiologic Database, and the
Register for Education Statistics, and the Register of Family Income. RESULTS:
Study I: A total of 16,509 procedures were registered in the DugaBase by 31
December 2010. The database completeness has increased from 38.2% to 93.2% during
the years. According to the validation, all 200 medical records were retrieved.
The overall percentage agreement between medical records and the DugaBase was at
least 90% for selected key variables: procedure code, date, hospital department,
use of antibiotics, prior surgery, height, weight, parity, and smoking. Study II:
In the study period, 20,629 urogynaecological procedures were performed in
Denmark and reported to the DugaBase. For approximately one third of these women,
the patient questionnaires on severity of symptoms and quality of life were
completed both pre- and postoperatively, and thus included. After both UI and POP
surgery, more than 80% had improved symptoms and showed a significant improvement
in quality of life. Study III: A total of 2,151 women with a primary UI procedure
were included. Of these, 358 (16.6%) were exposed to symptom-relieving drugs
preoperatively, and 1,793 (83.4%) were not. Preoperative usage of symptom
relieving drugs was the strongest risk factor of postoperative use, both within 0
60 days OR (adjusted) = 33.0 (95% confidence interval (CI) 20.0-54.7)) and 61-365
days OR (adjusted) = 7.2 (95% CI 5.4-9.6)). Adjusted for age, procedure type,
calendar year, comorbidity, preoperative use of oestrogen, educational level, and
personal annual income. Only a minority of preoperative non-users started using
symptom-relieving drugs postoperatively. Study IV: The same study population as
in study III. Of the 2,151 women, 496 (23.1%) were antibiotic users prior to
surgery, and 1,655 (76.9%) were non-users. Preoperative usages of antibiotics for
UTI was a strong risk factor of postoperative use of the same antibiotics, both
within 0-60 days OR (adjusted) = 2.6 (95% CI 2.9-3.5), and within 61-356 days OR
(adjusted) = 4.5 (95% CI 3.5-5.7)). Adjusted for age, procedure type, calendar
year, comorbidity, preoperative use of oestrogen, educational level, and personal
annual income. Comorbidity and procedure types were found to be significant risk
factors as well, although less important than preoperative antibiotic use.
CONCLUSIONS: Due to a high completeness and data of high validity the DugaBase
offers a unique possibility for continuing quality assessment of
urogynaecological surgery in Denmark, as well as for future research. Surgeries
for UI and POP performed in Danish women were effective in alleviating symptoms
of UI and POP and improvement in quality of life based on patient reported
outcome measures. Our pharmacoepidemiological studies showed that preoperative
use of symptom-relieving drugs and antibiotics for UTI were strong risk factors
of postoperative usage of the same drugs.
PMID- 26441399
TI - Maternal pelvic size, fetal growth and risk of stroke in adult offspring in a
large Swedish cohort.
AB - Earlier research suggests that maternal pelvic size is associated with
offspring's stroke risk in later life. We followed 6362 men and women from
Uppsala, Sweden, born between 1915 and 1929 from 1964 to 2008 to assess whether
maternal pelvic size was associated with incidence of thrombotic stroke (TS),
haemorrhagic stroke (HS) and other stroke (OS). Offspring whose mothers had a
flat pelvis had lower birth weight and birth-weight-for-gestational-age compared
with those who did not. Inverse linear associations of birth-weight-for
gestational-age were observed with TS and OS. Female offspring whose mothers had
a flat pelvis had increased risk of TS, but flat pelvis was not associated with
other types of stroke. A smaller difference between intercristal and interspinous
diameters and a smaller external conjugate diameter were independently associated
with HS, whereas no pelvic measurements were associated with OS. We conclude that
a smaller pelvis in women may impact the health of their offspring in adulthood.
PMID- 26441400
TI - Dextromethorphan Addiction Mediated Through the NMDA System: Common Pathways With
Alcohol?
AB - Dextromethorphan, an antitussive (cough suppressant) drug of the morphinan class
with sedative and dissociative properties found in cough syrup and other over-the
counter products, is also a substance of abuse, seen primarily in young adults
all over the world. A case of dextromethorphan use disorder is presented in a 45
year-old women. Her repeated attempts at abstinence were unsuccessful secondary
to continued intense cravings. Treatment with topiramate resulted in complete
resolution of her cravings. Topiramate was chosen empirically because of a common
action with dextromethorphan in the NMDA system. Genetic testing was obtained and
the patient was found to be a carrier of the GRIK1 rs2832407(C:C) allele. The
(C:C) allele has been associated with an increased risk of alcohol use disorder
and a treatment response of patients with heavy drinking to topiramate. This case
provides an opportunity to discuss personalized medicine (treatment options aided
by the use of genetic testing) and the possible shared genetic susceptibility for
dependence in 2 substances of abuse.
PMID- 26441402
TI - Clinicians' Beliefs and Practices Regarding Drug Use Care of Their Community
Health Center Patients.
AB - OBJECTIVES: Integration of behavioral health including substance use problems
into primary care is an essential benefit that federally qualified health centers
(FQHCs) will offer as part of the Affordable Care Act. This study explores FQHC
primary care clinicians' beliefs and practices regarding illicit drug use
assessment and treatment. METHODS: We administered a 10-minute questionnaire to
68 primary care clinicians of 5 FQHCs in Los Angeles. RESULTS: Clinicians
expressed limited confidence in their ability to address patients' illicit drug
use, scoring on average 3.31 on a 5-point Likert scale. Two thirds reported that
they assess for drug use routinely "at every visit" and/or "at annual visits."
When asked how often they counsel regarding drug use (on a 5-point Likert scale
from "never" to "always"), the median response was 4 ("usually"). Regarding their
perspectives on the best practical resource for addressing drug use in their
clinics, 45.6% named primary care clinicians. A minority (29.4%) of clinicians
had completed a clinical rotation dealing with substance use, and 27.2% reported
receiving more than 10 hours of training regarding substance use problems.
Having a substance use rotation was associated with greater confidence in drug
use assessment and treatment (P < 0.01). More hours of substance use training was
associated with greater confidence (P = 0.01) and routinely addressing substance
use in their patients (P = 0.04). CONCLUSIONS: Although two thirds of the
surveyed clinicians assess for drug use routinely, and on average, report that
they usually address drug use, clinicians' confidence in substance use care seems
to be suboptimal, but both confidence and routinely addressing substance use are
associated with increased substance use education. Improving clinicians' training
and integrating drug use care in FQHCs may improve confidence in substance use
care and facilitate the Affordable Care Act's mandate to integrate behavioral
health into routine FQHC primary care.
PMID- 26441401
TI - Longitudinal Modeling of the Association Between Transmissible Risk, Affect
During Drug Use and Development of Substance Use Disorder.
AB - OBJECTIVE: This longitudinal investigation examined the hypothesis that
subjective experience during consumption of preferred drugs mediates the
association of transmissible risk for substance use disorder (SUD) measured in
childhood and adolescence, and SUD diagnosis in adulthood. Transmissible risk
denotes the psychological characteristics having intergenerational continuity
between parents and their biological children. METHODS: The transmissible
liability index (TLI) was administered to four hundred eighty-three 10 to 12-year
old boys (baseline). Follow-up evaluations were conducted when the boys attained
12-14, 16, 19, and 22 years of age, using age-specific versions of the TLI.
Frequency of consumption of the participants' three most preferred drugs, affect
on an ordinary day, affect while under influence of the preferred substances, and
presence/absence of current SUD were assessed at 22 years of age. RESULTS:
Consumption frequency of preferred drugs among boys mediates the association of
transmissible risk during childhood, and adolescence and SUD diagnosis in
adulthood. Severity of negative affect on a drug-free day predicts frequency of
consumption of preferred drugs, which, in turn, predicts severity of negative
affect during the drug use event. Neither affect on a drug-free day nor affect
during the drug use event mediates the association of transmissible risk and SUD.
CONCLUSIONS: Affect on drug-free days, and while under influence of preferred
substances, covary with consumption frequency; however, affect is not related to
transmissible SUD risk or SUD outcome.
PMID- 26441403
TI - Patterns of call communication between group-housed zebra finches change during
the breeding cycle.
AB - Vocal signals such as calls play a crucial role for survival and successful
reproduction, especially in group-living animals. However, call interactions and
call dynamics within groups remain largely unexplored because their relation to
relevant contexts or life-history stages could not be studied with individual
level resolution. Using on-bird microphone transmitters, we recorded the
vocalisations of individual zebra finches (Taeniopygia guttata) behaving freely
in social groups, while females and males previously unknown to each other passed
through different stages of the breeding cycle. As birds formed pairs and shifted
their reproductive status, their call repertoire composition changed. The
recordings revealed that calls occurred non-randomly in fine-tuned vocal
interactions and decreased within groups while pair-specific patterns emerged.
Call-type combinations of vocal interactions changed within pairs and were
associated with successful egg-laying, highlighting a potential fitness relevance
of calling dynamics in communication systems.
PMID- 26441405
TI - Analysis of Moving-Coil Actuator Jet Injectors for Viscous Fluids.
AB - OBJECTIVE: A jet injector is a device that can be used to deliver liquid drugs
through the skin using a fluid jet, without the use of a needle. Most jet
injectors are designed and used for the delivery of inviscid liquids, and are not
optimized for the delivery of viscous drug compounds. To better understand the
requirements for delivering viscous drugs, we have developed a mathematical model
of the electromechanics of a moving-coil actuated jet injector as it delivers
viscous fluids. METHODS: The model builds upon previous work by incorporating the
nonlinear electrical properties of the motor, compliant elements of the
mechanical piston and ampoule system, and the effect of viscosity on injector
characteristics. The model has been validated by monitoring the movement of the
piston tip and measurements of the jet force. RESULTS: The results of the model
indicate that the jet speed is diminished with increasing fluid viscosity, but
overshoot and ringing in the jet speed is unaffected. However, a stiffer ampoule
and piston will allow for a better control of the jet speed profile during an
injection, and reduce ringing. CONCLUSION: We identified that the piston friction
coefficient, the compliance of the injector components, and the viscous
properties of the fluid are important determinants of performance when jet
injecting viscous fluids. SIGNIFICANCE: By expanding upon previous jet injector
models, this study has provided informative simulations of jet injector
characteristics and performance. The model can be used to guide the design of
future jet injectors for viscous fluids.
PMID- 26441404
TI - Cell-to-cell infection by HIV contributes over half of virus infection.
AB - Cell-to-cell viral infection, in which viruses spread through contact of infected
cell with surrounding uninfected cells, has been considered as a critical mode of
virus infection. However, since it is technically difficult to experimentally
discriminate the two modes of viral infection, namely cell-free infection and
cell-to-cell infection, the quantitative information that underlies cell-to-cell
infection has yet to be elucidated, and its impact on virus spread remains
unclear. To address this fundamental question in virology, we quantitatively
analyzed the dynamics of cell-to-cell and cell-free human immunodeficiency virus
type 1 (HIV-1) infections through experimental-mathematical investigation. Our
analyses demonstrated that the cell-to-cell infection mode accounts for
approximately 60% of viral infection, and this infection mode shortens the
generation time of viruses by 0.9 times and increases the viral fitness by 3.9
times. Our results suggest that even a complete block of the cell-free infection
would provide only a limited impact on HIV-1 spread.
PMID- 26441406
TI - Iterative Correction Scheme Based on Discrete Cosine Transform and L1
Regularization for Fluorescence Molecular Tomography With Background
Fluorescence.
AB - GOAL: High-intensity background fluorescence is generally encountered in
fluorescence molecular tomography (FMT), because of the accumulation of
fluorescent probes in nontarget tissues or the existence of autofluorescence in
biological tissues. The reconstruction results are affected or even distorted by
the background fluorescence, especially when the distribution of fluorescent
targets is relatively sparse. The purpose of this paper is to reduce the negative
effect of background fluorescence on FMT reconstruction. METHODS: After each
iteration of the Tikhonov regularization algorithm, 3-D discrete cosine transform
is adopted to filter the intermediate results. And then, a sparsity constraint
step based on L1 regularization is applied to restrain the energy of the
objective function. RESULTS: Phantom experiments with different fluorescence
intensities of homogeneous and heterogeneous background are carried out to
validate the performance of the proposed scheme. The results show that the
reconstruction quality can be improved with the proposed iterative correction
scheme. CONCLUSION AND SIGNIFICANCE: The influence of background fluorescence in
FMT can be reduced effectively because of the filtering of the intermediate
results, the detail preservation, and noise suppression of L1 regularization.
PMID- 26441407
TI - Elastic Stability of Concentric Tube Robots Subject to External Loads.
AB - Concentric tube robots, which are comprised of precurved elastic tubes that are
concentrically arranged, are being developed for many medical interventions. The
shape of the robot is determined by the rotation and translation of the tubes
relative to each other, and also by any external forces applied by the
environment. As the tubes rotate and translate relative to each other, elastic
potential energy caused by tube bending and twisting can accumulate; if a
configuration is not locally elastically stable, then a dangerous snapping motion
may occur as energy is suddenly released. External loads on the robot also
influence elastic stability. In this paper, we provide a second-order sufficient
condition, and also a separate necessary condition, for elastic stability. Using
methods of optimal control theory, we show that these conditions apply to general
concentric tube robot designs subject to arbitrary conservative external loads.
They can be used to assess the stability of candidate robot configurations. Our
results are validated via comparison with other known stability criteria, and
their utility is demonstrated by an application to stable path planning.
PMID- 26441409
TI - Biomimetic Accommodating Intraocular Lens Using a Valved Deformable Liquid
Balloon.
AB - OBJECTIVE: Presbyopia is a common age-related condition that prevents people from
focusing on near objects. The etiology of presbyopia continues to be debated, but
the end effect of all postulated mechanisms is the lack of deformation of the
human lens. Using our understanding of the biomechanical properties of the
natural human lens, we created a unique accommodating intraocular lens. Although
this lens can be used for lenticular disease such as myopia and hyperoperopia,
this study addresses the needs of cataract patients with presbyopia. METHODS: The
lens was implanted into presbyopic human cadaver eyes. Focal length of the lens
was measured with simulated muscle contraction. Lens dimensions were measured
using artificial tissue and a finite-element analysis (FEA) to simulate
accommodation. Lens power was measured at various fill volumes. Accelerated soak
testing for an equivalent of 7.4 years was performed and lens weight and optical
transmittance were measured. RESULTS: Previously presbyopic human eyes were able
to accommodate between 2.0 and 7.4 diopters after lens implantation. FEA and lens
measurements demonstrated a change in curvature of the anterior and posterior
portions of the lens during accommodation. After accelerated aging, lens weight
remained unchanged and optical transmission was 96%. Lens power increased with
fill volume. CONCLUSION: A deformable liquid lens reversed presbyopia, can be
individualized by optically adjusting for each patient, is stable for long
periods of time, and is compatible with minimally invasive surgical techniques.
SIGNIFICANCE: A deformable liquid-filled lens can significantly improve
accommodation over the presbyopic natural lens.
PMID- 26441408
TI - Behavioral Informatics and Computational Modeling in Support of Proactive Health
Management and Care.
AB - Health-related behaviors are among the most significant determinants of health
and quality of life. Improving health behavior is an effective way to enhance
health outcomes and mitigate the escalating challenges arising from an
increasingly aging population and the proliferation of chronic diseases. Although
it has been difficult to obtain lasting improvements in health behaviors on a
wide scale, advances at the intersection of technology and behavioral science may
provide the tools to address this challenge. In this paper, we describe a vision
and an approach to improve health behavior interventions using the tools of
behavioral informatics, an emerging transdisciplinary research domain based on
system-theoretic principles in combination with behavioral science and
information technology. The field of behavioral informatics has the potential to
optimize interventions through monitoring, assessing, and modeling behavior in
support of providing tailored and timely interventions. We describe the
components of a closed-loop system for health interventions. These components
range from fine grain sensor characterizations to individual-based models of
behavior change. We provide an example of a research health coaching platform
that incorporates a closed-loop intervention based on these multiscale models.
Using this early prototype, we illustrate how the optimized and personalized
methodology and technology can support self-management and remote care. We note
that despite the existing examples of research projects and our platform,
significant future research is required to convert this vision to full-scale
implementations.
PMID- 26441410
TI - Real-Time Visual Tracking of Deformable Objects in Robot-Assisted Surgery.
AB - One of the most challenging problems in robot-assisted surgical systems is to
provide surgical realism at interactive simulation rates. The proposed visual
tracking system can track and register object deformations in real time using a
physically based formulation, despite the occlusions produced by the robotic
system itself. The results obtained provide an accurate visual representation of
the deformed solid and will thus enable new assistance approaches to help
surgeons during surgical procedures.
PMID- 26441411
TI - Electrophysiology Catheter Detection and Reconstruction From Two Views in
Fluoroscopic Images.
AB - Electrophysiology (EP) studies and catheter ablation have become important
treatment options for several types of cardiac arrhythmias. We present a novel
image-based approach for automatic detection and 3-D reconstruction of EP
catheters where the physician marks the catheter to be reconstructed by a single
click in each image. The result can be used to provide 3-D information for
enhanced navigation throughout EP procedures. Our approach involves two X-ray
projections acquired from different angles, and it is based on two steps: First,
we detect the catheter in each view after manual initialization using a graph
search method. Then, the detection results are used to reconstruct a full 3-D
model of the catheter based on automatically determined point pairs for
triangulation. An evaluation on 176 different clinical fluoroscopic images
yielded a detection rate of 83.4%. For measuring the error, we used the coupling
distance which is a more accurate quality measure than the average point-wise
distance to a reference. For successful outcomes, the 2-D detection error was 1.7
mm +/-1.2 mm. Using successfully detected catheters for reconstruction, we
obtained a reconstruction error of 1.8 mm +/-1.1 mm on phantom data. On clinical
data, our method yielded a reconstruction error of 2.2 mm +/-2.2 mm.
PMID- 26441412
TI - Improving Computer-Aided Detection Using Convolutional Neural Networks and Random
View Aggregation.
AB - Automated computer-aided detection (CADe) has been an important tool in clinical
practice and research. State-of-the-art methods often show high sensitivities at
the cost of high false-positives (FP) per patient rates. We design a two-tiered
coarse-to-fine cascade framework that first operates a candidate generation
system at sensitivities ~ 100% of but at high FP levels. By leveraging existing
CADe systems, coordinates of regions or volumes of interest (ROI or VOI) are
generated and function as input for a second tier, which is our focus in this
study. In this second stage, we generate 2D (two-dimensional) or 2.5D views via
sampling through scale transformations, random translations and rotations. These
random views are used to train deep convolutional neural network (ConvNet)
classifiers. In testing, the ConvNets assign class (e.g., lesion, pathology)
probabilities for a new set of random views that are then averaged to compute a
final per-candidate classification probability. This second tier behaves as a
highly selective process to reject difficult false positives while preserving
high sensitivities. The methods are evaluated on three data sets: 59 patients for
sclerotic metastasis detection, 176 patients for lymph node detection, and 1,186
patients for colonic polyp detection. Experimental results show the ability of
ConvNets to generalize well to different medical imaging CADe applications and
scale elegantly to various data sets. Our proposed methods improve performance
markedly in all cases. Sensitivities improved from 57% to 70%, 43% to 77%, and
58% to 75% at 3 FPs per patient for sclerotic metastases, lymph nodes and colonic
polyps, respectively.
PMID- 26441413
TI - Improving the Accuracy of Registration-Based Biomechanical Analysis: A Finite
Element Approach to Lung Regional Strain Quantification.
AB - Tissue deformation plays an important role in lung physiology, as lung parenchyma
largely deforms during spontaneous ventilation. However, excessive regional
deformation may lead to lung injury, as observed in patients undergoing
mechanical ventilation. Thus, the accurate estimation of regional strain has
recently received great attention in the intensive care community. In this work,
we assess the accuracy of regional strain maps computed from direct
differentiation of B-Spline (BS) interpolations, a popular technique employed in
non-rigid registration of lung computed tomography (CT) images. We show that,
while BS-based registration methods give excellent results for the deformation
transformation, the strain field directly computed from BS derivatives results in
predictions that largely oscillate, thus introducing important errors that can
even revert the sign of strain. To alleviate such spurious behavior, we present a
novel finite-element (FE) method for the regional strain analysis of lung CT
images. The method follows from a variational strain recovery formulation, and
delivers a continuous approximation to the strain field in arbitrary domains.
From analytical benchmarks, we show that the FE method results in errors that are
a fraction of those found for the BS method, both in an average and pointwise
sense. The application of the proposed FE method to human lung CT images results
in 3D strain maps are heterogeneous and smooth, showing high consistency with
specific ventilation maps reported in the literature. We envision that the
proposed FE method will considerably improve the accuracy of image-based
biomechanical analysis, making it reliable enough for routine medical
applications.
PMID- 26441414
TI - Color Image Demosaicing Using Iterative Residual Interpolation.
AB - A recently developed demosaicing methodology, called residual interpolation (RI),
has demonstrated superior performance over the conventional color-component
difference interpolation. However, it has been observed that the existing RI
based methods fail to fully exploit the potential of RI strategy on the
reconstruction of the most important G channel, as only the R and B channels are
restored through the RI strategy. Since any reconstruction error introduced in
the G channel will be carried over into the demosaicing process of the other two
channels, this makes the restoration of the G channel highly instrumental to the
quality of the final demosaiced image. In this paper, a novel iterative RI (IRI)
process is developed for reconstructing a highly accurate G channel first; in
essence, it can be viewed as an iterative refinement process for the estimation
of those missing pixel values on the G channel. The key novelty of the proposed
IRI process is that all the three channels will mutually guide each other until a
stopping criterion is met. Based on the restored G channel, the mosaiced R and B
channels will be, respectively, reconstructed by exploiting the existing RI
method without iteration. Extensive simulations conducted on two commonly-used
test datasets for demosaicing algorithms have demonstrated that our algorithm has
achieved the best performance in most cases, compared with the existing state-of
the-art demosaicing methods on both objective and subjective performance
evaluations.
PMID- 26441415
TI - Edge-Preserving Decomposition-Based Single Image Haze Removal.
AB - Single image haze removal is under-constrained, because the number of freedoms is
larger than the number of observations. In this paper, a novel edge-preserving
decomposition-based method is introduced to estimate transmission map for a haze
image so as to design a single image haze removal algorithm from the Koschmiedars
law without using any prior. In particular, weighted guided image filter is
adopted to decompose simplified dark channel of the haze image into a base layer
and a detail layer. The transmission map is estimated from the base layer, and it
is applied to restore the haze-free image. The experimental results on different
types of images, including haze images, underwater images, and normal images
without haze, show the performance of the proposed algorithm.
PMID- 26441416
TI - A Boosted Multi-Task Model for Pedestrian Detection With Occlusion Handling.
AB - Pedestrian detection is a challenging problem in computer vision, and has
achieved impressive progress in recent years. However, the current state-of-the
art methods suffer from significant performance decline with increasing occlusion
level of pedestrians. A common approach for occlusion handling is to train a set
of occlusion-specific detectors and merge their results directly, but these
detectors are trained independently and the relationship among them is ignored.
In this paper, we consider pedestrian detection in different occlusion levels as
different but related problems, and propose a boosted multi-task model to jointly
consider their relatedness and differences. The proposed model adopts multi-task
learning algorithm to map pedestrians in different occlusion levels to a common
space, where all models corresponding to different occlusion levels are
constrained to share a common set of features, and a boosted detector is then
constructed to distinguish pedestrians from background. The proposed approach is
evaluated on three challenging pedestrian detection data sets, including Caltech,
TUD-Brussels, and INRIA, and achieves superior performances against state of the
art in the literature on different occlusion-specific test sets.
PMID- 26441417
TI - Local inverse tone curve learning for high dynamic range image scalable
compression.
AB - This paper presents a scalable high dynamic range (HDR) image coding scheme in
which the base layer is a low dynamic range version of the image that may have
been generated by an arbitrary tone mapping operator (TMO). No restriction is
imposed on the TMO, which can be either global or local, so as to fully respect
the artistic intent of the producer. Our method successfully handles the case of
complex local TMOs thanks to a block-wise and non-linear approach. A novel
template-based interlayer prediction (ILP) is designed in order to perform the
inverse tone mapping of a block without the need to transmit any additional
parameter to the decoder. This method enables the use of a more accurate inverse
tone mapping model than the simple linear regression commonly used for block-wise
ILP. In addition, this paper shows that a linear adjustment of the initially
predicted block can further improve the overall coding performance by using an
efficient encoding scheme of the scaling parameters. Our experiments have shown
an average bitrate saving of 47% on the HDR enhancement layer, compared with the
previous local ILP methods.
PMID- 26441418
TI - Interface Detection Using a Quenched-Noise Version of the Edwards-Wilkinson
Equation.
AB - We report here a multipurpose dynamic-interface-based segmentation tool, suitable
for segmenting planar, cylindrical, and spherical surfaces in 3D. The method is
fast enough to be used conveniently even for large images. Its implementation is
straightforward and can be easily realized in many environments. Its memory
consumption is low, and the set of parameters is small and easy to understand.
The method is based on the Edwards-Wilkinson equation, which is traditionally
used to model the equilibrium fluctuations of a propagating interface under the
influence of temporally and spatially varying noise. We report here an adaptation
of this equation into multidimensional image segmentation, and its efficient
discretization.
PMID- 26441419
TI - Single Object Tracking With Fuzzy Least Squares Support Vector Machine.
AB - Single object tracking, in which a target is often initialized manually in the
first frame and then is tracked and located automatically in the subsequent
frames, is a hot topic in computer vision. The traditional tracking-by-detection
framework, which often formulates tracking as a binary classification problem,
has been widely applied and achieved great success in single object tracking.
However, there are some potential issues in this formulation. For instance, the
boundary between the positive and negative training samples is fuzzy, and the
objectives of tracking and classification are inconsistent. In this paper, we
attempt to address the above issues from the fuzzy system perspective and propose
a novel tracking method by formulating tracking as a fuzzy classification
problem. First, we introduce the fuzzy strategy into tracking and propose a novel
fuzzy tracking framework, which can measure the importance of the training
samples by assigning different memberships to them and offer more strict spatial
constraints. Second, we develop a fuzzy least squares support vector machine (FLS
SVM) approach and employ it to implement a concrete tracker. In particular, the
primal form, dual form, and kernel form of FLS-SVM are analyzed and the
corresponding closed-form solutions are derived for efficient realizations.
Besides, a least squares regression model is built to control the update
adaptively, retaining the robustness of the appearance model. The experimental
results demonstrate that our method can achieve comparable or superior
performance to many state-of-the-art methods.
PMID- 26441420
TI - Bitplane Image Coding With Parallel Coefficient Processing.
AB - Image coding systems have been traditionally tailored for multiple instruction,
multiple data (MIMD) computing. In general, they partition the (transformed)
image in codeblocks that can be coded in the cores of MIMD-based processors. Each
core executes a sequential flow of instructions to process the coefficients in
the codeblock, independently and asynchronously from the others cores. Bitplane
coding is a common strategy to code such data. Most of its mechanisms require
sequential processing of the coefficients. The last years have seen the upraising
of processing accelerators with enhanced computational performance and power
efficiency whose architecture is mainly based on the single instruction, multiple
data (SIMD) principle. SIMD computing refers to the execution of the same
instruction to multiple data in a lockstep synchronous way. Unfortunately,
current bitplane coding strategies cannot fully profit from such processors due
to inherently sequential coding task. This paper presents bitplane image coding
with parallel coefficient (BPC-PaCo) processing, a coding method that can process
many coefficients within a codeblock in parallel and synchronously. To this end,
the scanning order, the context formation, the probability model, and the
arithmetic coder of the coding engine have been re-formulated. The experimental
results suggest that the penalization in coding performance of BPC-PaCo with
respect to the traditional strategies is almost negligible.
PMID- 26441421
TI - Effective Clipart Image Vectorization through Direct Optimization of Bezigons.
AB - Bezigons, i.e., closed paths composed of Bezier curves, have been widely employed
to describe shapes in image vectorization results. However, most existing
vectorization techniques infer the bezigons by simply approximating an
intermediate vector representation (such as polygons). Consequently, the
resultant bezigons are sometimes imperfect due to accumulated errors, fitting
ambiguities, and a lack of curve priors, especially for low-resolution images. In
this paper, we describe a novel method for vectorizing clipart images. In
contrast to previous methods, we directly optimize the bezigons rather than using
other intermediate representations; therefore, the resultant bezigons are not
only of higher fidelity compared with the original raster image but also more
reasonable because they were traced by a proficient expert. To enable such
optimization, we have overcome several challenges and have devised a
differentiable data energy as well as several curve-based prior terms. To improve
the efficiency of the optimization, we also take advantage of the local control
property of bezigons and adopt an overlapped piecewise optimization strategy. The
experimental results show that our method outperforms both the current state-of
the-art method and commonly used commercial software in terms of bezigon quality.
PMID- 26441422
TI - Event-Related Beta EEG Changes During Active, Passive Movement and Functional
Electrical Stimulation of the Lower Limb.
AB - A number of electroencephalographic (EEG) studies have reported on event-related
desynchronization/synchronization (ERD/ERS) during active movements, passive
movements, and the movements induced by functional electrical stimulation (FES).
However, the quantitative differences in ERD values and affected frequency bands
associated with the lower limb have not been discussed. The goal of this paper
was to quantitatively compare the ERD patterns during active movement, passive
movement and FES-induced movement of the lower limb. 64-channel EEG signals were
recorded to investigate the brain oscillatory patterns during active movement,
passive movement and FES-induced movement of the lower limb in twelve healthy
subjects. And passive movement and FES-induced movement were also performed in a
hemiplegic stroke patient. For healthy subjects, FES-induced movement presented
significantly higher characteristic frequency of central beta ERD while there was
no significant difference in ERD values compared with active or passive movement.
Meanwhile, beta ERD values of FES-induced movement were significantly correlated
with those of active movement, and spatial distribution of beta ERD pattern for
FES-induced movement was more correlated with that for active movement. In
addition, the stroke patient presented central ERD patterns during FES-induced
movement, while no ERD with similar frequencies could be found during passive
movement. This work implies that the EEG oscillatory pattern under FES-induced
movement tends more towards active movement instead of passive movement. The
quantification of ERD patterns could be expected as a potential technique to
evaluate the brain response during FES-induced movement.
PMID- 26441423
TI - Robustness and Reliability of Synergy-Based Myocontrol of a Multiple Degree of
Freedom Robotic Arm.
AB - In this study, we test the feasibility of the synergy- based approach for
application in the realistic and clinically oriented framework of multi-degree of
freedom (DOF) robotic control. We developed and tested online ten able-bodied
subjects in a semi-supervised method to achieve simultaneous, continuous control
of two DOFs of a robotic arm, using muscle synergies extracted from upper limb
muscles while performing flexion-extension movements of the elbow and shoulder
joints in the horizontal plane. To validate the efficacy of the synergy-based
approach in extracting reliable control signals, compared to the simple muscle
pair method typically used in commercial applications, we evaluated the
repeatability of the algorithm over days, the effect of the arm dynamics on the
control performance, and the robustness of the control scheme to the presence of
co-contraction between pairs of antagonist muscles. Results showed that, without
the need for a daily calibration, all subjects were able to intuitively and
easily control the synergy-based myoelectric interface in different scenarios,
using both dynamic and isometric muscle contractions. The proposed control scheme
was shown to be robust to co-contraction between antagonist muscles, providing
better performance compared to the traditional muscle-pair approach. The current
study is a first step toward user-friendly application of synergy-based
myocontrol of assistive robotic devices.
PMID- 26441424
TI - Towards a Computer Aided Prognosis for Brain Glioblastomas Tumor Growth
Estimation.
AB - Bridging the gap between mathematical and biological models and clinical
applications could be considered as one of the new challenges of medical image
analysis over the ten last years. This paper presents an advanced and convivial
algorithm for brain glioblastomas tumor growth modelization. The brain
glioblastomas tumor region would be extracted using a fast distribution matching
developed algorithm based on global pixel wise information. A new model to
simulate the tumor growth based on two major elements: cellular automata and fast
marching method (CFMM) has been developed and used to estimate the brain tumor
evolution during the time. On the basis of this model, experiments were carried
out on twenty pathological MRI selected cases that were carefully discussed with
the clinical part. The obtained simulated results were validated with ground
truth references (real tumor growth measure) using dice metric parameter. As
carefully discussed with the clinical partner, experimental results showed that
our proposed algorithm for brain glioblastomas tumor growth model proved a good
agreement. Our main purpose behind this research was of course to make advances
and progress during clinical explorations helping therefore radiologists in their
diagnosis. Clinical decisions and guidelines would be hence so more focused with
such an advanced tool that could help clinicians and ensuring more accuracy and
objectivity.
PMID- 26441425
TI - A High Sensitivity Impedimetric Biosensor Using the Tannin From Quercusmacrolepis
as Biorecognition Element for Heavy Metals Detection.
AB - A new poly(vinylchloride) (PVC) membrane electrode based on tannin from the bark
of Quercusmacrolepis (acorn) as the ionophore was prepared and modified onto the
surface of a gold electrode. The electrochemical impedance spectroscopy (EIS)
technique was used to study the sensitivity of the electrode that was modified
with a thin layer of polymeric biomembrane, in order to detect heavy metals ions
in solution. The device shows a good sensitivity for Zn(2+), Ni(2+) ions and a
little less for Cd(2+). The electrode indicates a good linear response for the
three metals over a wide concentration range from 1.0*10(-9) to 1.0*10(-4) M,
with a detection limit of 1.0*10(-9) M.
PMID- 26441426
TI - Quantitative Verification of Dynamic Wedge Dose Distribution Using a 2D
Ionization Chamber Array.
AB - The accuracy of two calculation algorithms of the Eclipse 8.9 treatment planning
system (TPS)--the anisotropic analytic algorithm (AAA) and pencil-beam
convolution (PBC)--in modeling the enhanced dynamic wedge (EDW) was investigated.
Measurements were carried out for 6 and 18 MV photon beams using a 2D ionization
chamber array. Accuracy of the TPS was evaluated using a gamma index analysis
with the following acceptance criteria for dose differences (DD) and distance to
agreement (DTA): 3%/3 mm and 2%/2 mm. The TPS models the dose distribution
accurately except for 20*20 cm(2) field size, 60 ( degrees ) and 45 ( degrees )
wedge angles using PBC at 6 MV photon energy. For these latter fields, the pass
rate and the mean value of gamma were less than 90% and more than 0.5,
respectively at the (3%/3 mm) acceptance criteria. In addition, an accuracy level
of (2%/2 mm) was achieved using AAA with better agreement for 18 MV photon
energy.
PMID- 26441427
TI - A Cascade Random Forests Algorithm for Predicting Protein-Protein Interaction
Sites.
AB - Protein-protein interactions exist ubiquitously and play important roles in the
life cycles of living cells. The interaction sites (residues) are essential to
understanding the underlying mechanisms of protein-protein interactions. Previous
research has demonstrated that the accurate identification of protein-protein
interaction sites (PPIs) is helpful for developing new therapeutic drugs because
many drugs will interact directly with those residues. Because of its significant
potential in biological research and drug development, the prediction of PPIs has
become an important topic in computational biology. However, a severe data
imbalance exists in the PPIs prediction problem, where the number of the majority
class samples (non-interacting residues) is far larger than that of the minority
class samples (interacting residues). Thus, we developed a novel cascade random
forests algorithm (CRF) to address the serious data imbalance that exists in the
PPIs prediction problem. The proposed CRF resolves the negative effect of data
imbalance by connecting multiple random forests in a cascade-like manner, each of
which is trained with a balanced training subset that includes all minority
samples and a subset of majority samples using an effective ensemble protocol.
Based on the proposed CRF, we implemented a new sequence-based PPIs predictor,
called CRF-PPI, which takes the combined features of position-specific scoring
matrices, averaged cumulative hydropathy, and predicted relative solvent
accessibility as model inputs. Benchmark experiments on both the cross validation
and independent validation datasets demonstrated that the proposed CRF-PPI
outperformed the state-of-the-art sequence-based PPIs predictors. The source code
for CRF-PPI and the benchmark datasets are available online at
http://csbio.njust.edu.cn/bioinf/CRF-PPI for free academic use.
PMID- 26441428
TI - Spatial Resolution Improvement of EEG Source Reconstruction Using swLORETA.
AB - Electroencephalography (EEG) and magnetic resonance imaging (MRI) are noninvasive
neuro-imaging modalities largely used in neurology explorations. MRI is
considered as a static modality and could be so important for anatomy by its high
spatial resolution. EEG, on the other hand, is an important tool permitting to
image temporal dynamic activities of the human brain. Fusion of these two
essential modalities would be hence a so emerging research domain targeting to
explore brain activities with the MRI static modality. Our present research
investigates a sophisticated approach for localization of the cerebral activity
that could be involved by the dynamic EEG modality and carefully illustrated
within MRI static modality. Such careful cerebral activity localization would be
first based on an advanced methodology yielding therefore a singular value
decomposition-based lead field weighting to sLORETA method formalism, for solving
in fact the inverse problem in the EEG. The conceived method for source
localization, carried out on different cases of simulated dipoles experiments,
showed satisfactory results. Different cases of simulated dipoles experiments and
metrics were used to confirm the reliability of the proposed method. The
experimental results confirm that our method presents a flexible and robust tool
for EEG source imaging.
PMID- 26441429
TI - Practical Guidelines for Incorporating Knowledge-Based and Data-Driven Strategies
into the Inference of Gene Regulatory Networks.
AB - Modeling gene regulatory networks (GRNs) is essential for conceptualizing how
genes are expressed and how they influence each other. Typically, a reverse
engineering approach is employed; this strategy is effective in reproducing
possible fitting models of GRNs. To use this strategy, however, two daunting
tasks must be undertaken: one task is to optimize the accuracy of inferred
network behaviors; and the other task is to designate valid biological topologies
for target networks. Although existing studies have addressed these two tasks for
years, few of the studies can satisfy both of the requirements simultaneously. To
address these difficulties, we propose an integrative modeling framework that
combines knowledge-based and data-driven input sources to construct biological
topologies with their corresponding network behaviors. To validate the proposed
approach, a real dataset collected from the cell cycle of the yeast S. cerevisiae
is used. The results show that the proposed framework can successfully infer
solutions that meet the requirements of both the network behaviors and biological
structures. Therefore, the outcomes are exploitable for future in vivo
experimental design.
PMID- 26441430
TI - Assessing Short-Term Voltage Stability of Electric Power Systems by a
Hierarchical Intelligent System.
AB - In the smart grid paradigm, growing integration of large-scale intermittent
renewable energies has introduced significant uncertainties to the operations of
an electric power system. This makes real-time dynamic security assessment (DSA)
a necessity to enable enhanced situational-awareness against the risk of
blackouts. Conventional DSA methods are mainly based on the time-domain
simulation, which are insufficiently fast and knowledge-poor. In recent years,
the intelligent system (IS) strategy has been identified as a promising approach
to facilitate real-time DSA. While previous works mainly concentrate on the rotor
angle stability, this paper focuses on another yet increasingly important dynamic
insecurity phenomenon-the short-term voltage instability, which involves fast and
complex load dynamics. The problem is modeled as a classification subproblem for
transient voltage collapse and a prediction subproblem for unacceptable dynamic
voltage deviation. A hierarchical IS is developed to address the two subproblems
sequentially. The IS is based on ensemble learning of random-weights neural
networks and is implemented in an offline training, a real-time application, and
an online updating pattern. The simulation results on the New England 39-bus
system verify its superiority in both learning speed and accuracy over some state
of-the-art learning algorithms.
PMID- 26441431
TI - Robust Kernel Low-Rank Representation.
AB - Recently, low-rank representation (LRR) has shown promising performance in many
real-world applications such as face clustering. However, LRR may not achieve
satisfactory results when dealing with the data from nonlinear subspaces, since
it is originally designed to handle the data from linear subspaces in the input
space. Meanwhile, the kernel-based methods deal with the nonlinear data by
mapping it from the original input space to a new feature space through a kernel
induced mapping. To effectively cope with the nonlinear data, we first propose
the kernelized version of LRR in the clean data case. We also present a closed
form solution for the resultant optimization problem. Moreover, to handle
corrupted data, we propose the robust kernel LRR (RKLRR) approach, and develop an
efficient optimization algorithm to solve it based on the alternating direction
method. In particular, we show that both the subproblems in our optimization
algorithm can be efficiently and exactly solved, and it is guaranteed to obtain a
globally optimal solution. Besides, our proposed algorithm can also solve the
original LRR problem, which is a special case of our RKLRR when using the linear
kernel. In addition, based on our new optimization technique, the kernelization
of some variants of LRR can be similarly achieved. Comprehensive experiments on
synthetic data sets and real-world data sets clearly demonstrate the efficiency
of our algorithm, as well as the effectiveness of RKLRR and the kernelization of
two variants of LRR.
PMID- 26441432
TI - A Survey of Mobile Phone Sensing, Self-Reporting, and Social Sharing for
Pervasive Healthcare.
AB - The current institution-based model for healthcare service delivery faces
enormous challenges posed by an aging population and the prevalence of chronic
diseases. For this reason, pervasive healthcare, i.e., the provision of
healthcare services to individuals anytime anywhere, has become a major focus for
the research community. In this paper, we map out the current state of pervasive
healthcare research by presenting an overview of three emerging areas in
personalized health monitoring, namely: 1) mobile phone sensing via in-built or
external sensors, 2) self-reporting for manually captured health information,
such as symptoms and behaviors, and 3) social sharing of health information
within the individual's community. Systems deployed in a real-life setting as
well as proofs-of-concept for achieving pervasive health are presented, in order
to identify shortcomings and increase our understanding of the requirements for
the next generation of pervasive healthcare systems addressing these three areas.
PMID- 26441433
TI - Nonsmooth Finite-Time Synchronization of Switched Coupled Neural Networks.
AB - This paper is concerned with the finite-time synchronization (FTS) issue of
switched coupled neural networks with discontinuous or continuous activations.
Based on the framework of nonsmooth analysis, some discontinuous or continuous
controllers are designed to force the coupled networks to synchronize to an
isolated neural network. Some sufficient conditions are derived to ensure the FTS
by utilizing the well-known finite-time stability theorem for nonlinear systems.
Compared with the previous literatures, such synchronization objective will be
realized when the activations and the controllers are both discontinuous. The
obtained results in this paper include and extend the earlier works on the
synchronization issue of coupled networks with Lipschitz continuous conditions.
Moreover, an upper bound of the settling time for synchronization is estimated.
Finally, numerical simulations are given to demonstrate the effectiveness of the
theoretical results.
PMID- 26441434
TI - A Hybrid Approach to Clustering in Big Data.
AB - Clustering of big data has received much attention recently. In this paper, we
present a new clusiVAT algorithm and compare it with four other popular data
clustering algorithms. Three of the four comparison methods are based on the well
known, classical batch k -means model. Specifically, we use k -means, single pass
k -means, online k -means, and clustering using representatives (CURE) for
numerical comparisons. clusiVAT is based on sampling the data, imaging the
reordered distance matrix to estimate the number of clusters in the data
visually, clustering the samples using a relative of single linkage (SL), and
then noniteratively extending the labels to the rest of the data-set using the
nearest prototype rule. Previous work has established that clusiVAT produces true
SL clusters in compact-separated data. We have performed experiments to show that
k -means and its modified algorithms suffer from initialization issues that cause
many failures. On the other hand, clusiVAT needs no initialization, and almost
always finds partitions that accurately match ground truth labels in labeled
data. CURE also finds SL type partitions but is much slower than the other four
algorithms. In our experiments, clusiVAT proves to be the fastest and most
accurate of the five algorithms; e.g., it recovers 97% of the ground truth labels
in the real world KDD-99 cup data (4 292 637 samples in 41 dimensions) in 76 s.
PMID- 26441435
TI - Discriminative Tracking Using Tensor Pooling.
AB - How to effectively organize local descriptors to build a global representation
has a critical impact on the performance of vision tasks. Recently, local sparse
representation has been successfully applied to visual tracking, owing to its
discriminative nature and robustness against local noise and partial occlusions.
Local sparse codes computed with a template actually form a three-order tensor
according to their original layout, although most existing pooling operators
convert the codes to a vector by concatenating or computing statistics on them.
We argue that, compared to pooling vectors, the tensor form could deliver more
intrinsic structural information for the target appearance, and can also avoid
high dimensionality learning problems suffered in concatenation-based pooling
methods. Therefore, in this paper, we propose to represent target templates and
candidates directly with sparse coding tensors, and build the appearance model by
incrementally learning on these tensors. We propose a discriminative framework to
further improve robustness of our method against drifting and environmental
noise. Experiments on a recent comprehensive benchmark indicate that our method
performs better than state-of-the-art trackers.
PMID- 26441436
TI - Detection-Free Multiobject Tracking by Reconfigurable Inference With Bundle
Representations.
AB - This paper presents a conceptually simple but effective approach to track
multiobject in videos without requiring elaborate supervision (i.e., training
object detectors or templates offline). Our framework performs a bi-layer
inference of spatio-temporal grouping to exploit rich appearance and motion
information in the observed sequence. First, we generate a robust middle-level
video representation based on clustered point tracks, namely video bundles. Each
bundle encapsulates a chunk of point tracks satisfying both spatial proximity and
temporal coherency. Taking the video bundles as vertices, we build a spatio
temporal graph that incorporates both competitive and compatible relations among
vertices. The multiobject tracking can be then phrased as a graph partition
problem under the Bayesian framework, and we solve it by developing a
reconfigurable belief propagation (BP) algorithm. This algorithm improves the
traditional BP method by allowing a converged solution to be reconfigured during
optimization, so that the inference can be reactivated once it gets stuck in
local minima and thus conduct more reliable results. In the experiments, we
demonstrate the superior performances of our approach on the challenging
benchmarks compared with other state-of-the-art methods.
PMID- 26441437
TI - Adaptive and Energy Efficient Walking in a Hexapod Robot Under Neuromechanical
Control and Sensorimotor Learning.
AB - The control of multilegged animal walking is a neuromechanical process, and to
achieve this in an adaptive and energy efficient way is a difficult and
challenging problem. This is due to the fact that this process needs in real
time: 1) to coordinate very many degrees of freedom of jointed legs; 2) to
generate the proper leg stiffness (i.e., compliance); and 3) to determine joint
angles that give rise to particular positions at the endpoints of the legs. To
tackle this problem for a robotic application, here we present a neuromechanical
controller coupled with sensorimotor learning. The controller consists of a
modular neural network for coordinating 18 joints and several virtual agonist
antagonist muscle mechanisms (VAAMs) for variable compliant joint motions. In
addition, sensorimotor learning, including forward models and dual-rate learning
processes, is introduced for predicting foot force feedback and for online tuning
the VAAMs' stiffness parameters. The control and learning mechanisms enable the
hexapod robot advanced mobility sensor driven-walking device (AMOS) to achieve
variable compliant walking that accommodates different gaits and surfaces. As a
consequence, AMOS can perform more energy efficient walking, compared to other
small legged robots. In addition, this paper also shows that the tight
combination of neural control with tunable muscle-like functions, guided by
sensory feedback and coupled with sensorimotor learning, is a way forward to
better understand and solve adaptive coordination problems in multilegged
locomotion.
PMID- 26441438
TI - Methods for Improving the Curvature of Steerable Needles in Biological Tissue.
AB - OBJECTIVE: Robotic needle steering systems have the potential to improve
percutaneous interventions such as radiofrequency ablation of liver tumors, but
steering techniques described to date have not achieved sufficiently small radius
of curvature in biological tissue to be relevant to this application. In this
study, the impact of tip geometry on steerable needle curvature was examined.
METHODS: Finite-element simulations and experiments with bent-tip needles in ex
vivo liver tissue were performed. Motivated by the results of this analysis, a
new articulated-tip steerable needle was designed, in which a distal section is
actively switched by a robotic system between a straight tip (resulting in a
straight path) and a bent tip (resulting in a curved path). RESULTS: Selection of
tip length and angle can greatly improve curvature, with radius of curvature
below 5 cm in liver tissue possible through judicious selection of these
parameters. An articulated-tip mechanism allows the tip length and angle to be
increased, while the straight configuration allows the needle tip to still pass
through an introducer sheath and rotate inside the body. CONCLUSION: Validation
testing in liver tissue shows that the new articulated-tip steerable needle
achieves smaller radius of curvature compared to bent-tip needles described in
previous work. SIGNIFICANCE: Steerable needles with optimized tip parameters,
which can generate tight curves in liver tissue, increase the clinical relevance
of needle steering to percutaneous interventions.
PMID- 26441439
TI - A Motion Interference-Insensitive Flexible Dry Electrode.
AB - OBJECTIVE: A novel dry electrode is developed to improve the comfortability and
the capability of alleviating motion interference by combining microneedles array
(MNA) with flexible substrate. METHODS: Silicon MNA with sharp tips and limited
height is fabricated and transferred on a flexible Polydimethylsiloxane (PDMS)
substrate through bonding. Poly (3, 4-ethylenedioxythiophene) doped with poly
(styrenesulfonate) (PEDOT/PSS) is coated on the surface of flexible MNA to form a
conductive layer. RESULTS: Flexible dry electrode with 1.2 cm diameter is
successfully fabricated. The mean impedance magnitudes (measured on skin) at 10
Hz are 61.2 +/-31.3 kOmega.cm(2) for flexible dry electrode, while the values are
114.9 +/-36.1 kOmega.cm(2) for wet electrode and 335.7 +/-110.5 kOmega.cm(2) for
flexible planar dry electrode, respectively. In the process of biopotential
recording, the flexible dry electrode has the similar performance as that of wet
electrode. It exhibits more stable recording stability than rigid dry electrode
in the movement state. CONCLUSION: By integrating flexible PDMS substrate, sharp
and hard MNA structure, as well as PEDOT/PSS coated surface together, a novel dry
electrode is developed to meet the comfortable and antimotion interference
requirement of wearable equipment. SIGNIFICANCE: The novel flexible dry electrode
provides a simple and comfortable method to record biopotential signals in daily
life.
PMID- 26441440
TI - Comparison of Auditory Middle-Latency Responses From Two Deconvolution Methods at
40 Hz.
AB - GOAL: Auditory middle-latency responses (MLRs) are reported to be particularly
susceptible to stimulation rate. Deconvolution methods are necessary to unwrap
the overlapping responses at a high rate under the linear superposition
assumption. This study aims to investigate and compare the MLR characteristics at
high and conventional stimulation rates. METHODS: The characteristics were
examined in healthy adults by using two closely related deconvolution paradigms,
namely continuous-loop averaging deconvolution and multirate steady-state
averaging deconvolution at a mean rate of 40 Hz, and a conventional low rate of 5
Hz. RESULTS: The morphology and stability of the MLRs can benefit from a high
rate stimulation. It appears that stimulation sequencing strategies of
deconvolution methods exerted divergent rate effects on MLR characteristics,
which might be associated with different adaptation mechanisms. CONCLUSION: MLRs
obtained by two deconvolution methods and the conventional reference feature
differently from one another. SIGNIFICANCE: These findings have critical
implications in our current understanding of the rate effects on MLR
characteristics which may inspire further studies to explore the characteristics
of evoked responses at high rates and deconvolution paradigms.
PMID- 26441441
TI - Spiking Neural Network With Distributed Plasticity Reproduces Cerebellar Learning
in Eye Blink Conditioning Paradigms.
AB - GOAL: In this study, we defined a realistic cerebellar model through the use of
artificial spiking neural networks, testing it in computational simulations that
reproduce associative motor tasks in multiple sessions of acquisition and
extinction. METHODS: By evolutionary algorithms, we tuned the cerebellar
microcircuit to find out the near-optimal plasticity mechanism parameters that
better reproduced human-like behavior in eye blink classical conditioning, one of
the most extensively studied paradigms related to the cerebellum. We used two
models: one with only the cortical plasticity and another including two
additional plasticity sites at nuclear level. RESULTS: First, both spiking
cerebellar models were able to well reproduce the real human behaviors, in terms
of both "timing" and "amplitude", expressing rapid acquisition, stable late
acquisition, rapid extinction, and faster reacquisition of an associative motor
task. Even though the model with only the cortical plasticity site showed good
learning capabilities, the model with distributed plasticity produced faster and
more stable acquisition of conditioned responses in the reacquisition phase. This
behavior is explained by the effect of the nuclear plasticities, which have slow
dynamics and can express memory consolidation and saving. CONCLUSIONS: We showed
how the spiking dynamics of multiple interactive neural mechanisms implicitly
drive multiple essential components of complex learning processes. SIGNIFICANCE:
This study presents a very advanced computational model, developed together by
biomedical engineers, computer scientists, and neuroscientists. Since its
realistic features, the proposed model can provide confirmations and suggestions
about neurophysiological and pathological hypotheses and can be used in
challenging clinical applications.
PMID- 26441442
TI - MAPS: A Quantitative Radiomics Approach for Prostate Cancer Detection.
AB - This paper presents a quantitative radiomics feature model for performing
prostate cancer detection using multiparametric MRI (mpMRI). It incorporates a
novel tumor candidate identification algorithm to efficiently and thoroughly
identify the regions of concern and constructs a comprehensive radiomics feature
model to detect tumorous regions. In contrast to conventional automated
classification schemes, this radiomics-based feature model aims to ground its
decisions in a way that can be interpreted and understood by the diagnostician.
This is done by grouping features into high-level feature categories which are
already used by radiologists to diagnose prostate cancer: Morphology, Asymmetry,
Physiology, and Size (MAPS), using biomarkers inspired by the PI-RADS guidelines
for performing structured reporting on prostate MRI. Clinical mpMRI data were
collected from 13 men with histology-confirmed prostate cancer and labeled by an
experienced radiologist. These annotated data were used to train classifiers
using the proposed radiomics-driven feature model in order to evaluate the
classification performance. The preliminary experimental results indicated that
the proposed model outperformed each of its constituent feature groups as well as
a comparable conventional mpMRI feature model. A further validation of the
proposed algorithm will be conducted using a larger dataset as future work.
PMID- 26441443
TI - A New Feature-Enhanced Speckle Reduction Method Based on Multiscale Analysis for
Ultrasound B-Mode Imaging.
AB - GOAL: Effective speckle reduction in ultrasound B-mode imaging is important for
enhancing the image quality and improving the accuracy in image analysis and
interpretation. In this paper, a new feature-enhanced speckle reduction (FESR)
method based on multiscale analysis and feature enhancement filtering is proposed
for ultrasound B-mode imaging. In FESR, clinical features (e.g., boundaries and
borders of lesions) are selectively emphasized by edge, coherence, and contrast
enhancement filtering from fine to coarse scales while simultaneously suppressing
speckle development via robust diffusion filtering. In the simulation study, the
proposed FESR method showed statistically significant improvements in edge
preservation, mean structure similarity, speckle signal-to-noise ratio, and
contrast-to-noise ratio (CNR) compared with other speckle reduction methods,
e.g., oriented speckle reducing anisotropic diffusion (OSRAD), nonlinear
multiscale wavelet diffusion (NMWD), the Laplacian pyramid-based nonlinear
diffusion and shock filter (LPNDSF), and the Bayesian nonlocal means filter
(OBNLM). Similarly, the FESR method outperformed the OSRAD, NMWD, LPNDSF, and
OBNLM methods in terms of CNR, i.e., 10.70 +/- 0.06 versus 9.00 +/- 0.06, 9.78 +/
0.06, 8.67 +/- 0.04, and 9.22 +/- 0.06 in the phantom study, respectively.
Reconstructed B-mode images that were developed using the five speckle reduction
methods were reviewed by three radiologists for evaluation based on each
radiologist's diagnostic preferences. All three radiologists showed a significant
preference for the abdominal liver images obtained using the FESR methods in
terms of conspicuity, margin sharpness, artificiality, and contrast, p<0.0001.
For the kidney and thyroid images, the FESR method showed similar improvement
over other methods. However, the FESR method did not show statistically
significant improvement compared with the OBNLM method in margin sharpness for
the kidney and thyroid images. These results demonstrate that the proposed FESR
method can improve the image quality of ultrasound B-mode imaging by enhancing
the visualization of lesion features while effectively suppressing speckle noise.
PMID- 26441444
TI - Distributed Multi-Target Tracking and Data Association in Vision Networks.
AB - Distributed algorithms have recently gained immense popularity. With regards to
computer vision applications, distributed multi-target tracking in a camera
network is a fundamental problem. The goal is for all cameras to have accurate
state estimates for all targets. Distributed estimation algorithms work by
exchanging information between sensors that are communication neighbors. Vision
based distributed multi-target state estimation has at least two characteristics
that distinguishes it from other applications. First, cameras are directional
sensors and often neighboring sensors may not be sensing the same targets, i.e.,
they are naive with respect to that target. Second, in the presence of clutter
and multiple targets, each camera must solve a data association problem. This
paper presents an information-weighted, consensus-based, distributed multi-target
tracking algorithm referred to as the Multi-target Information Consensus (MTIC)
algorithm that is designed to address both the naivety and the data association
problems. It converges to the centralized minimum mean square error estimate. The
proposed MTIC algorithm and its extensions to non-linear camera models, termed as
the Extended MTIC (EMTIC), are robust to false measurements and limited resources
like power, bandwidth and the real-time operational requirements. Simulation and
experimental analysis are provided to support the theoretical results.
PMID- 26441445
TI - Approximate Fisher Kernels of Non-iid Image Models for Image Categorization.
AB - The bag-of-words (BoW) model treats images as sets of local descriptors and
represents them by visual word histograms. The Fisher vector (FV) representation
extends BoW, by considering the first and second order statistics of local
descriptors. In both representations local descriptors are assumed to be
identically and independently distributed (iid), which is a poor assumption from
a modeling perspective. It has been experimentally observed that the performance
of BoW and FV representations can be improved by employing discounting
transformations such as power normalization. In this paper, we introduce non-iid
models by treating the model parameters as latent variables which are integrated
out, rendering all local regions dependent. Using the Fisher kernel principle we
encode an image by the gradient of the data log-likelihood w.r.t. the model hyper
parameters. Our models naturally generate discounting effects in the
representations; suggesting that such transformations have proven successful
because they closely correspond to the representations obtained for non-iid
models. To enable tractable computation, we rely on variational free-energy
bounds to learn the hyper-parameters and to compute approximate Fisher kernels.
Our experimental evaluation results validate that our models lead to performance
improvements comparable to using power normalization, as employed in state-of-the
art feature aggregation methods.
PMID- 26441446
TI - Towards Personalized Statistical Deformable Model and Hybrid Point Matching for
Robust MR-TRUS Registration.
AB - Registration and fusion of magnetic resonance (MR) and 3D transrectal ultrasound
(TRUS) images of the prostate gland can provide high-quality guidance for
prostate interventions. However, accurate MR-TRUS registration remains a
challenging task, due to the great intensity variation between two modalities,
the lack of intrinsic fiducials within the prostate, the large gland deformation
caused by the TRUS probe insertion, and distinctive biomechanical properties in
patients and prostate zones. To address these challenges, a personalized model-to
surface registration approach is proposed in this study. The main contributions
of this paper can be threefold. First, a new personalized statistical deformable
model (PSDM) is proposed with the finite element analysis and the patient
specific tissue parameters measured from the ultrasound elastography. Second, a
hybrid point matching method is developed by introducing the modality independent
neighborhood descriptor (MIND) to weight the Euclidean distance between points to
establish reliable surface point correspondence. Third, the hybrid point matching
is further guided by the PSDM for more physically plausible deformation
estimation. Eighteen sets of patient data are included to test the efficacy of
the proposed method. The experimental results demonstrate that our approach
provides more accurate and robust MR-TRUS registration than state-of-the-art
methods do. The averaged target registration error is 1.44 mm, which meets the
clinical requirement of 1.9 mm for the accurate tumor volume detection. It can be
concluded that the presented method can effectively fuse the heterogeneous image
information in the elastography, MR, and TRUS to attain satisfactory image
alignment performance.
PMID- 26441447
TI - Video Compression Artifact Reduction via Spatio-Temporal Multi-Hypothesis
Prediction.
AB - Annoying compression artifacts exist in most of lossy coded videos at low bit
rates, which are caused by coarse quantization of transform coefficients or
motion compensation from distorted frames. In this paper, we propose a
compression artifact reduction approach that utilizes both the spatial and the
temporal correlation to form multi-hypothesis predictions from spatio-temporal
similar blocks. For each transform block, three predictions with their
reliabilities are estimated, respectively. The first prediction is constructed by
inversely quantizing transform coefficients directly, and its reliability is
determined by the variance of quantization noise. The second prediction is
derived by representing each transform block with a temporal auto-regressive
(TAR) model along its motion trajectory, and its corresponding reliability is
estimated from local prediction errors of the TAR model. The last prediction
infers the original coefficients from similar blocks in non-local regions, and
its reliability is estimated based on the distribution of coefficients in these
similar blocks. Finally, all the predictions are adaptively fused according to
their reliabilities to restore high-quality videos. The experimental results show
that the proposed method can efficiently reduce most of the compression artifacts
and improve both subjective and objective quality of block transform coded
videos.
PMID- 26441448
TI - Normalized cut-based saliency detection by adaptive multi-level region merging.
AB - Existing salient object detection models favor over-segmented regions upon which
saliency is computed. Such local regions are less effective on representing
object holistically and degrade emphasis of entire salient objects. As a result,
the existing methods often fail to highlight an entire object in complex
background. Toward better grouping of objects and background, in this paper, we
consider graph cut, more specifically, the normalized graph cut (Ncut) for
saliency detection. Since the Ncut partitions a graph in a normalized energy
minimization fashion, resulting eigenvectors of the Ncut contain good cluster
information that may group visual contents. Motivated by this, we directly induce
saliency maps via eigenvectors of the Ncut, contributing to accurate saliency
estimation of visual clusters. We implement the Ncut on a graph derived from a
moderate number of superpixels. This graph captures both intrinsic color and edge
information of image data. Starting from the superpixels, an adaptive multi-level
region merging scheme is employed to seek such cluster information from Ncut
eigenvectors. With developed saliency measures for each merged region,
encouraging performance is obtained after across-level integration. Experiments
by comparing with 13 existing methods on four benchmark datasets, including MSRA
1000, SOD, SED, and CSSD show the proposed method, Ncut saliency, results in
uniform object enhancement and achieves comparable/better performance to the
state-of-the-art methods.
PMID- 26441449
TI - Beyond Explicit Codebook Generation: Visual Representation Using Implicitly
Transferred Codebooks.
AB - The bag-of-visual-words model plays a very important role for visual
applications. Local features are first extracted and then encoded to get the
histogram-based image representation. To encode local features, a proper codebook
is needed. Usually, the codebook has to be generated for each data set which
means the codebook is data set dependent. Besides, the codebook may be biased
when we only have a limited number of training images. Moreover, the codebook has
to be pre-learned which cannot be updated quickly, especially when applied for
online visual applications. To solve the problems mentioned above, in this paper,
we propose a novel implicit codebook transfer method for visual representation.
Instead of explicitly generating the codebook for the new data set, we try to
make use of pre-learned codebooks using non-linear transfer. This is achieved by
transferring the pre-learned codebooks with non-linear transformation and use
them to reconstruct local features with sparsity constraints. The codebook does
not need to be explicitly generated but can be implicitly transferred. In this
way, we are able to make use of pre-learned codebooks for new visual applications
by implicitly learning the codebook and the corresponding encoding parameters for
image representation. We apply the proposed method for image classification and
evaluate the performance on several public image data sets. Experimental results
demonstrate the effectiveness and efficiency of the proposed method.
PMID- 26441450
TI - Feature Surfaces in Symmetric Tensor Fields Based on Eigenvalue Manifold.
AB - Three-dimensional symmetric tensor fields have a wide range of applications in
solid and fluid mechanics. Recent advances in the (topological) analysis of 3D
symmetric tensor fields focus on degenerate tensors which form curves. In this
paper, we introduce a number of feature surfaces, such as neutral surfaces and
traceless surfaces, into tensor field analysis, based on the notion of eigenvalue
manifold. Neutral surfaces are the boundary between linear tensors and planar
tensors, and the traceless surfaces are the boundary between tensors of positive
traces and those of negative traces. Degenerate curves, neutral surfaces, and
traceless surfaces together form a partition of the eigenvalue manifold, which
provides a more complete tensor field analysis than degenerate curves alone. We
also extract and visualize the isosurfaces of tensor modes, tensor isotropy, and
tensor magnitude, which we have found useful for domain applications in fluid and
solid mechanics. Extracting neutral and traceless surfaces using the Marching
Tetrahedra method can cause the loss of geometric and topological details, which
can lead to false physical interpretation. To robustly extract neutral surfaces
and traceless surfaces, we develop a polynomial description of them which enables
us to borrow techniques from algebraic surface extraction, a topic well
researched by the computer-aided design (CAD) community as well as the algebraic
geometry community. In addition, we adapt the surface extraction technique,
called A-patches, to improve the speed of finding degenerate curves. Finally, we
apply our analysis to data from solid and fluid mechanics as well as scalar field
analysis.
PMID- 26441451
TI - Detecting Multivariate Gene Interactions in RNA-Seq Data Using Optimal Bayesian
Classification.
AB - Differential gene expression testing is an analysis commonly applied to RNA-Seq
data. These statistical tests identify genes that are significantly different
across phenotypes. We extend this testing paradigm to multivariate gene
interactions from a classification perspective with the goal to detect novel gene
interactions for the phenotypes of interest. This is achieved through our novel
computational framework comprised of a hierarchical statistical model of the RNA
Seq processing pipeline and the corresponding optimal Bayesian classifier.
Through Markov Chain Monte Carlo sampling and Monte Carlo integration, we compute
quantities where no analytical formulation exists. The performance is then
illustrated on an expression dataset from a dietary intervention study where we
identify gene pairs that have low classification error yet were not identified as
differentially expressed. Additionally, we have released the software package to
perform OBC classification on RNA-Seq data under an open source license and is
available at http://bit.ly/obc_package.
PMID- 26441452
TI - Robust Multiobjective Controllability of Complex Neuronal Networks.
AB - This paper addresses robust multiobjective identification of driver nodes in the
neuronal network of a cat's brain, in which uncertainties in determination of
driver nodes and control gains are considered. A framework for robust
multiobjective controllability is proposed by introducing interval uncertainties
and optimization algorithms. By appropriate definitions of robust multiobjective
controllability, a robust nondominated sorting adaptive differential evolution
(NSJaDE) is presented by means of the nondominated sorting mechanism and the
adaptive differential evolution (JaDE). The simulation experimental results
illustrate the satisfactory performance of NSJaDE for robust multiobjective
controllability, in comparison with six statistical methods and two
multiobjective evolutionary algorithms (MOEAs): nondominated sorting genetic
algorithms II (NSGA-II) and nondominated sorting composite differential
evolution. It is revealed that the existence of uncertainties in choosing driver
nodes and designing control gains heavily affects the controllability of neuronal
networks. We also unveil that driver nodes play a more drastic role than control
gains in robust controllability. The developed NSJaDE and obtained results will
shed light on the understanding of robustness in controlling realistic complex
networks such as transportation networks, power grid networks, biological
networks, etc.
PMID- 26441453
TI - The Effects of Fluidic Loading on Underwater Contact Sensing with Robotic Fins
and Beams.
AB - As robots become more involved in underwater operations, understanding underwater
contact sensing with compliant systems is fundamental to engineering useful
haptic interfaces and vehicles. Despite knowledge of contact sensation in air,
little is known about contact sensing underwater and the impact of fluid on both
the robotic probe and the target object. The objective of this work is to
understand the effects of fluidic loading, fin webbing, and target object
geometry on strain sensation within compliant robotic fins and beams during
obstacle contact. General descriptions of obstacle contact were sought for strain
measurements in fins and beams. Multiple phases of contact were characterized
where the robot, fluid, and object interact to affect sensory signals. Unlike in
air, the underwater structure-fluid-structure interaction (SFSI) caused changes
to strain in each phase of contact. The addition of webbing to beams created a
mechanical coupling between adjacent beams, which changed contact strains.
Complex obstacle geometries tended to make contact less apparent and caused
stretch in fins. This work demonstrates several effects of fluidic loading on
strain sensing with compliant robotic beams and fins as they contact obstacles in
air and underwater, and provides guidance for future work in underwater active
sensing with compliant manipulators.
PMID- 26441455
TI - Space Structure and Clustering of Categorical Data.
AB - Learning from categorical data plays a fundamental role in such areas as pattern
recognition, machine learning, data mining, and knowledge discovery. To
effectively discover the group structure inherent in a set of categorical
objects, many categorical clustering algorithms have been developed in the
literature, among which k -modes-type algorithms are very representative because
of their good performance. Nevertheless, there is still much room for improving
their clustering performance in comparison with the clustering algorithms for the
numeric data. This may arise from the fact that the categorical data lack a clear
space structure as that of the numeric data. To address this issue, we propose,
in this paper, a novel data-representation scheme for the categorical data, which
maps a set of categorical objects into a Euclidean space. Based on the data
representation scheme, a general framework for space structure based categorical
clustering algorithms (SBC) is designed. This framework together with the
applications of two kinds of dissimilarities leads two versions of the SBC-type
algorithms. To verify the performance of the SBC-type algorithms, we employ as
references four representative algorithms of the k -modes-type algorithms.
Experiments show that the proposed SBC-type algorithms significantly outperform
the k -modes-type algorithms.
PMID- 26441454
TI - Design and Evaluation of a Cable-Driven fMRI-Compatible Haptic Interface to
Investigate Precision Grip Control.
AB - Our hands and fingers are involved in almost all activities of daily living and,
as such, have a disproportionately large neural representation. Functional
magnetic resonance imaging investigations into the neural control of the hand
have revealed great advances, but the harsh MRI environment has proven to be a
challenge to devices capable of delivering a large variety of stimuli necessary
for well-controlled studies. This paper presents a fMRI-compatible haptic
interface to investigate the neural mechanisms underlying precision grasp
control. The interface, located at the scanner bore, is controlled remotely
through a shielded electromagnetic actuation system positioned at the end of the
scanner bed and then through a high stiffness, low inertia cable transmission. We
present the system design, taking into account requirements defined by the
biomechanics and dynamics of the human hand, as well as the fMRI environment.
Performance evaluation revealed a structural stiffness of 3.3 N/mm, renderable
forces up to 94 N, and a position control bandwidth of at least 19 Hz. MRI
compatibility tests showed no degradation in the operation of the haptic
interface or the image quality. A preliminary fMRI experiment during a pilot
study validated the usability of the haptic interface, illustrating the
possibilities offered by this device.
PMID- 26441456
TI - MSDLSR: Margin Scalable Discriminative Least Squares Regression for Multicategory
Classification.
AB - In this brief, we propose a new margin scalable discriminative least squares
regression (MSDLSR) model for multicategory classification. The main motivation
behind the MSDLSR is to explicitly control the margin of DLSR model. We first
prove that the DLSR is a relaxation of the traditional L2 -support vector
machine. Based on this fact, we further provide a theorem on the margin of DLSR.
With this theorem, we add an explicit constraint on DLSR to restrict the number
of zeros of dragging values, so as to control the margin of DLSR. The new model
is called MSDLSR. Theoretically, we analyze the determination of the margin and
support vectors of MSDLSR. Extensive experiments illustrate that our method
outperforms the current state-of-the-art approaches on various machine leaning
and real-world data sets.
PMID- 26441457
TI - Robust Optimization-Based Coronary Artery Labeling From X-Ray Angiograms.
AB - In this paper, we present an efficient robust labeling method for coronary
arteries from X-ray angiograms based on energy optimization. The fundamental goal
of this research is to facilitate the analysis and diagnosis of interventional
surgery in the most efficient way, and such effort could also improve the
performance during doctor training, and surgery simulation and planning. Compared
to the prior state-of-the-art, our method is much more robust to resist noises
and is tolerant to even incomplete data because of the "built-in" nature of
global optimization. We start with a fully parallelized algorithm based on
Hessian matrix to extract the tubular structure from the X-ray angiograms as
vessel candidates. Then, instead of using the candidates directly, we use the
grow cut (Vezhnevets and V. Konouchine, Growcut: Interactive multi-label N-D
image segmentation by cellular automata, in Proc. of Graphicon, 2005, pp. 150
156.) method, which is similar to graph cut (Boykov et al. , Fast approximate
energy minimization via graph cuts, IEEE Trans. Pattern Anal. Mach. Intell. ,
vol. 23, no. 11, pp. 1222-1239, Nov. 2001.)but with better performance to extract
the precise vessel structure from the images. Next, we use the fast marching
method with second derivatives and cross neighbors to extract the accurate
skeleton segments. After that, we propose an efficient method based on iterative
closest point (Z. Zhang, Iterative point matching for registration of free-form
curves and surfaces, Int J. Comput. Vis., vol. 13, no. 2, pp. 119-152, 1994.) to
organize the skeleton segments by treating the continuity and similarity as extra
constraints. Finally, we formulate the vessel labeling problem as an energy
optimization problem and solve it using belief propagation. We also demonstrate
several typical applications including flow velocity estimation, heart beat
estimation, and vessel diameter estimation to show its practical uses in clinical
diagnosis and treatment. Our experiments exhibit the correctness and robustness,
as well as the high performance of our algorithm. We envision that our system
would be of high utility for diagnosis and therapy to treat vessel-related
diseases in a clinical setting in the near future.
PMID- 26441458
TI - Structure Sensitive Hashing With Adaptive Product Quantization.
AB - Hashing has been proved as an attractive solution to approximate nearest neighbor
search, owing to its theoretical guarantee and computational efficiency. Though
most of prior hashing algorithms can achieve low memory and computation
consumption by pursuing compact hash codes, however, they are still far beyond
the capability of learning discriminative hash functions from the data with
complex inherent structure among them. To address this issue, in this paper, we
propose a structure sensitive hashing based on cluster prototypes, which
explicitly exploits both global and local structures. An alternating optimization
algorithm, respectively, minimizing the quantization loss and spectral embedding
loss, is presented to simultaneously discover the cluster prototypes for each
hash function, and optimally assign unique binary codes to them satisfying the
affinity alignment between them. For hash codes of a desired length, an adaptive
bit assignment is further appended to the product quantization of the subspaces,
approximating the Hamming distances and meanwhile balancing the variance among
hash functions. Experimental results on four large-scale benchmarks CIFAR-10, NUS
WIDE, SIFT1M, and GIST1M demonstrate that our approach significantly outperforms
state-of-the-art hashing methods in terms of semantic and metric neighbor search.
PMID- 26441459
TI - Hierarchical Model Predictive Image-Based Visual Servoing of Underwater Vehicles
With Adaptive Neural Network Dynamic Control.
AB - This paper proposes a hierarchical image-based visual servoing (IBVS) strategy
for dynamic positioning of a fully actuated underwater vehicle. In the kinematic
loop, the desired velocity is generated by a nonlinear model predictive
controller, which optimizes a cost function of the predicted image trajectories
under the constraints of visibility and velocity. A velocity reference model,
representing the desired closed-loop vehicle dynamics, is integrated with an IBVS
kinematic model to predict the future trajectories. In the dynamic velocity
tracking loop, a neural-network-based model reference adaptive controller is
designed to ensure the convergence of the velocity tracking error in the presence
of uncertainties associated with vehicle dynamic parameters, water velocity, and
thrust forces. Comparative simulations with different control and system
configurations are performed to verify the effectiveness of the proposed scheme
and to illustrate the influences of the prediction horizon, cost function, closed
loop vehicle dynamics, and predictive velocity reference model on the IBVS system
performance.
PMID- 26441460
TI - Formation Control With Size Scaling Via a Complex Laplacian-Based Approach.
AB - We consider the control of formations of a leader-follower network, where the
objective is to steer a team of multiple mobile agents into a formation of
variable size. We assume that the shape description of the formation is known to
all the agents, which is captured by a complex-valued Laplacian associated with
the sensing graph, but the size scaling of the formation is not known or only
known to two agents, called the leaders in the network. A distributed linear
control strategy is developed in this paper such that the agents converge to the
desired formation shape, for which the size of the formation is determined by the
two leaders. Moreover, in order to make all agents in a formation move with a
common velocity, the distributed control law also incorporates a velocity
consensus component, which is implemented with the help of a communication
network that may, in general, be of different topology from the sensing graph.
Both the setup of single-integrator kinematics and the one of double-integrator
dynamics are addressed in the same framework except that the acceleration control
in the double-integrator setup has an extra damping term.
PMID- 26441461
TI - Vision-Based Human Tracking Control of a Wheeled Inverted Pendulum Robot.
AB - In this paper, a vision-based adaptive control is designed for a wheeled inverted
pendulum (WIP) robot to track a moving human target by integration of multisensor
data. A new algorithm is employed in the system to combine an OptiTrack camera
and a Kinect camera, such that more robust and efficient performance can be
achieved for human target detection and tracking. Robust adaptive control has
been developed for the WIP robot to maintain its balance on two wheels and to
follow the human target using visual feedback. Leader-follower control, dynamic
balance control and visual tracking are efficiently combined together to achieved
desired tracking and balancing performance. Extensive experiment studies have
been performed to test the effectiveness of the proposed control strategies.
PMID- 26441462
TI - Road Risk Modeling and Cloud-Aided Safety-Based Route Planning.
AB - This paper presents a safety-based route planner that exploits vehicle-to-cloud
to-vehicle (V2C2V) connectivity. Time and road risk index (RRI) are considered as
metrics to be balanced based on user preference. To evaluate road segment risk, a
road and accident database from the highway safety information system is mined
with a hybrid neural network model to predict RRI. Real-time factors such as time
of day, day of the week, and weather are included as correction factors to the
static RRI prediction. With real-time RRI and expected travel time, route
planning is formulated as a multiobjective network flow problem and further
reduced to a mixed-integer programming problem. A V2C2V implementation of our
safety-based route planning approach is proposed to facilitate access to real
time information and computing resources. A real-world case study, route planning
through the city of Columbus, Ohio, is presented. Several scenarios illustrate
how the "best" route can be adjusted to favor time versus safety metrics.
PMID- 26441463
TI - An Event-Triggered Approach to State Estimation for a Class of Complex Networks
With Mixed Time Delays and Nonlinearities.
AB - In this paper, the state estimation problem is investigated for a class of
discrete-time complex networks subject to nonlinearities, mixed delays, and
stochastic noises. A set of event-based state estimators is constructed so as to
reduce unnecessary data transmissions in the communication channel. Compared with
the traditional state estimator whose measurement signal is received under a
periodic clock-driven rule, the event-based estimator only updates the
measurement information from the sensors when the prespecified "event" is
violated. Attention is focused on the analysis and design problem of the event
based estimators for the addressed discrete-time complex networks such that the
estimation error is exponentially bounded in mean square. A combination of the
stochastic analysis approach and Lyapunov theory is employed to obtain sufficient
conditions for ensuring the existence of the desired estimators and the upper
bound of the estimation error is also derived. By using the convex optimization
technique, the gain parameters of the desired estimators are provided in an
explicit form. Finally, a simulation example is used to demonstrate the
effectiveness of the proposed estimation strategy.
PMID- 26441464
TI - Discontinuous Neural Networks for Finite-Time Solution of Time-Dependent Linear
Equations.
AB - This paper considers a class of nonsmooth neural networks with discontinuous hard
limiter (signum) neuron activations for solving time-dependent (TD) systems of
algebraic linear equations (ALEs). The networks are defined by the
subdifferential with respect to the state variables of an energy function given
by the L 1 norm of the error between the state and the TD-ALE solution. It is
shown that when the penalty parameter exceeds a quantitatively estimated
threshold the networks are able to reach in finite time, and exactly track
thereafter, the target solution of the TD-ALE. Furthermore, this paper discusses
the tightness of the estimated threshold and also points out key differences in
the role played by this threshold with respect to networks for solving time
invariant ALEs. It is also shown that these convergence results are robust with
respect to small perturbations of the neuron interconnection matrices. The
dynamics of the proposed networks are rigorously studied by using tools from
nonsmooth analysis, the concept of subdifferential of convex functions, and that
of solutions in the sense of Filippov of dynamical systems with discontinuous
nonlinearities.
PMID- 26441465
TI - EEG-Based Classification of Implicit Intention During Self-Relevant Sentence
Reading.
AB - From electroencephalography (EEG) data during self-relevant sentence reading, we
were able to discriminate two implicit intentions: 1) "agreement" and 2)
"disagreement" to the read sentence. To improve the classification accuracy,
discriminant features were selected based on Fisher score among EEG frequency
bands and electrodes. Especially, the time-frequency representation with Morlet
wavelet transforms showed clear differences in gamma, beta, and alpha band powers
at frontocentral area, and theta band power at centroparietal area. The best
classification accuracy of 75.5% was obtained by a support vector machine
classifier with the gamma band features at frontocentral area. This result may
enable a new intelligent user-interface which understands users' implicit
intention, i.e., unexpressed or hidden intention.
PMID- 26441466
TI - Effects of Social Network Exposure on Nutritional Learning: Development of an
Online Educational Platform.
AB - BACKGROUND: Social networking sites (SNSs) such as Facebook have the potential to
enhance online public health interventions, in part, as they provide social
exposure and reinforcement. OBJECTIVE: The objective of the study was to evaluate
whether social exposure provided by SNSs enhances the effects of online public
health interventions. METHODS: As a sample intervention, we developed Food Hero,
an online platform for nutritional education in which players feed a virtual
character according to their own nutritional needs and complete a set of virtual
sport challenges. The platform was developed in 2 versions: a "private version"
in which a user can see only his or her own score, and a "social version" in
which a user can see other players' scores, including preexisting Facebook
friends. We assessed changes in participants' nutritional knowledge using 4 quiz
scores and 3 menu-assembly scores. Monitoring feeding and exercising attempts
assessed engagement with the platform. RESULTS: The 2 versions of the platform
were randomly assigned between a study group (30 members receiving the social
version) and a control group (33 members, private version). The study group's
performance on the quizzes gradually increased over time, relative to that of the
control group, becoming significantly higher by the fourth quiz (P=.02).
Furthermore, the study group's menu-assembly scores improved over time compared
to the first score, whereas the control group's performance deteriorated. Study
group members spent an average of 3:40 minutes assembling each menu compared to
2:50 minutes in the control group, and performed an average of 1.58 daily sport
challenges, compared to 1.21 in the control group (P=.03). CONCLUSIONS: This work
focused on isolating the SNSs' social effects in order to help guide future
online interventions. Our results indicate that the social exposure provided by
SNSs is associated with increased engagement and learning in an online
nutritional educational platform.
PMID- 26441468
TI - Basal Temperature Measurement Using a Multi-Sensor Armband in Australian Young
Women: A Comparative Observational Study.
AB - BACKGROUND: The menstrual cycle is a key marker of health in women of
reproductive age. Monitoring ovulation is useful in health studies involving
young women. The upward shift in basal body temperature, which occurs shortly
after ovulation and continues until the next menses, is a potentially useful
marker of ovulation, which has been exploited in clinical and research settings.
OBJECTIVE: We investigated the utility of BodyMedia SenseWear (BMSW) in
monitoring ovulation in young women by analyzing the correlation and agreement of
basal temperatures measured using BMSW and a digital oral thermometer. METHODS:
Kappa statistics were used to determine the agreement in ovulation detection
between the two devices, for each participant, under each form of analysis.
Participants also completed an online questionnaire assessing the acceptability
of both devices. RESULTS: We recruited 16 participants with 15 of them providing
analyzable data (11 OCP non-users, 4 OCP users). Weak to moderate correlations
were observed between thermometer and BMSW temperature measurements averaged over
5 different time intervals. However, no agreement between methods was observed
using Bland-Altman plots. There was a significant difference in the range of
temperatures that each device recorded (thermometer: 35.3-37.2 degrees C, BMSW:
29.7-36.7 degrees C) with BMSW temperatures significantly lower than thermometer
temperatures: mean 34.6 degrees C (SD 1.2) versus 36.4 degrees C (SD 0.3)
respectively, P<.001. Poor agreement was observed between devices under
quantitative analysis of ovulation while fair agreement was observed under visual
analysis. Under both quantitative and visual analysis, there was 0% agreement for
evidence of ovulation. CONCLUSIONS: This study demonstrated the importance of
evaluating biomeasures collected using mobile monitoring devices by comparison
with standard methods. It revealed a relatively poor correlation between BMSW and
oral thermometer temperature readings and suggested that BMSW is unlikely to
detect an upward shift in basal body temperature. Participant behavior suggested
poor compliance in the use of BMSW for basal temperature measurement and that the
basal body temperature method may not be suitable for use in unselected samples
of young women. There is a need for research tools for monitoring ovulation that
are simple, self-administered, and inexpensive, yet appealing to young women.
PMID- 26441467
TI - Health Coaching Reduces HbA1c in Type 2 Diabetic Patients From a Lower
Socioeconomic Status Community: A Randomized Controlled Trial.
AB - BACKGROUND: Adoptions of health behaviors are crucial for maintaining good health
after type 2 diabetes mellitus (T2DM) diagnoses. However, adherence to
glucoregulating behaviors like regular exercise and balanced diet can be
challenging, especially for people living in lower-socioeconomic status (SES)
communities. Providing cost-effective interventions that improve self-management
is important for improving quality of life and the sustainability of health care
systems. OBJECTIVE: To evaluate a health coach intervention with and without the
use of mobile phones to support health behavior change in patients with type 2
diabetes. METHODS: In this noninferiority, pragmatic randomized controlled trial
(RCT), patients from two primary care health centers in Toronto, Canada, with
type 2 diabetes and a glycated hemoglobin/hemoglobin A1c (HbA1c) level of >=7.3%
(56.3 mmol/mol) were randomized to receive 6 months of health coaching with or
without mobile phone monitoring support. We hypothesized that both approaches
would result in significant HbA1c reductions, although health coaching with
mobile phone monitoring would result in significantly larger effects.
Participants were evaluated at baseline, 3 months, and 6 months. The primary
outcome was the change in HbA1c from baseline to 6 months (difference between and
within groups). Other outcomes included weight, waist circumference, body mass
index (BMI), satisfaction with life, depression and anxiety (Hospital Anxiety and
Depression Scale [HADS]), positive and negative affect (Positive and Negative
Affect Schedule [PANAS]), and quality of life (Short Form Health Survey-12 [SF
12]). RESULTS: A total of 138 patients were randomized and 7 were excluded for a
substudy; of the remaining 131, 67 were allocated to the intervention group and
64 to the control group. Primary outcome data were available for 97 participants
(74.0%). While both groups reduced their HbA1c levels, there were no significant
between-group differences in change of HbA1c at 6 months using intention-to-treat
(last observation carried forward [LOCF]) (P=.48) or per-protocol (P=.83)
principles. However, the intervention group did achieve an accelerated HbA1c
reduction, leading to a significant between-group difference at 3 months (P=.03).
This difference was reduced at the 6-month follow-up as the control group
continued to improve, achieving a reduction of 0.81% (8.9 mmol/mol) (P=.001)
compared with a reduction of 0.84% (9.2 mmol/mol)(P=.001) in the intervention
group. Intervention group participants also had significant decreases in weight
(P=.006) and waist circumference (P=.01) while controls did not. Both groups
reported improvements in mood, satisfaction with life, and quality of life.
CONCLUSIONS: Health coaching with and without access to mobile technology
appeared to improve glucoregulation and mental health in a lower-SES, T2DM
population. The accelerated improvement in the mobile phone group suggests the
connectivity provided may more quickly improve adoption and adherence to health
behaviors within a clinical diabetes management program. Overall, health coaching
in primary care appears to lead to significant benefits for patients from lower
SES communities with poorly controlled type 2 diabetes. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02036892; http://clinicaltrials.gov/ct2/show/NCT02036892
(Archived by WebCite at http://www.webcitation.org/6b3cJYJOD).
PMID- 26441469
TI - Current Theories on the Prevention of Severe Preeclampsia With Low-Molecular
Weight Heparin.
PMID- 26441471
TI - Modeling Localization of Amplitude-Panned Virtual Sources in Sagittal Planes.
AB - Vector-base amplitude panning (VBAP) aims at creating virtual sound sources at
arbitrary directions within multichannel sound reproduction systems. However,
VBAP does not consistently produce listener-specific monaural spectral cues that
are essential for localization of sound sources in sagittal planes, including the
front-back and up-down dimensions. In order to better understand the limitations
of VBAP, a functional model approximating human processing of spectro-spatial
information was applied to assess accuracy in sagittal-plane localization of
virtual sources created by means of VBAP. First, we evaluated VBAP applied on two
loudspeakers in the median plane, and then we investigated the directional
dependence of the localization accuracy in several three-dimensional loudspeaker
arrangements designed in layers of constant elevation. The model predicted a
strong dependence on listeners' individual head-related transfer functions, on
virtual source directions, and on loudspeaker arrangements. In general, the
simulations showed a systematic degradation with increasing polar-angle span
between neighboring loudspeakers. For the design of VBAP systems, predictions
suggest that spans up to 40 degrees polar angle yield a good trade-off between
system complexity and localization accuracy. Special attention should be paid to
the frontal region where listeners are most sensitive to deviating spectral cues.
PMID- 26441472
TI - Attracting Views and Going Viral: How Message Features and News-Sharing Channels
Affect Health News Diffusion.
AB - This study examined how intrinsic as well as perceived message features affect
the extent to which online health news stories prompt audience selections and
social retransmissions, and how news-sharing channels (e-mail vs. social media)
shape what goes viral. The study analyzed actual behavioral data on audience
viewing and sharing of New York Times health news articles, and associated
article content and context data. News articles with high informational utility
and positive sentiment invited more frequent selections and retransmissions.
Articles were also more frequently selected when they presented controversial,
emotionally evocative, and familiar content. Informational utility and novelty
had stronger positive associations with e-mail-specific virality, while emotional
evocativeness, content familiarity, and exemplification played a larger role in
triggering social media-based retransmissions.
PMID- 26441470
TI - Endothelial Mineralocorticoid Receptor Deletion Prevents Diet-Induced Cardiac
Diastolic Dysfunction in Females.
AB - Overnutrition and insulin resistance are especially prominent risk factors for
the development of cardiac diastolic dysfunction in females. We recently reported
that consumption of a Western diet (WD) containing excess fat (46%), sucrose
(17.5%), and high fructose corn syrup (17.5%) for 16 weeks resulted in cardiac
diastolic dysfunction and aortic stiffening in young female mice and that these
abnormalities were prevented by mineralocorticoid receptor blockade. Herein, we
extend those studies by testing whether WD-induced diastolic dysfunction and
factors contributing to diastolic impairment, such as cardiac fibrosis,
hypertrophy, inflammation, and impaired insulin signaling, are modulated by
excess endothelial cell mineralocorticoid receptor signaling. Four-week-old
female endothelial cell mineralocorticoid receptor knockout and wild-type mice
were fed mouse chow or WD for 4 months. WD feeding resulted in prolonged
relaxation time, impaired diastolic septal wall motion, and increased left
ventricular filling pressure indicative of diastolic dysfunction. This occurred
in concert with myocardial interstitial fibrosis and cardiomyocyte hypertrophy
that were associated with enhanced profibrotic (transforming growth factor
beta1/Smad) and progrowth (S6 kinase-1) signaling, as well as myocardial
oxidative stress and a proinflammatory immune response. WD also induced
cardiomyocyte stiffening, assessed ex vivo using atomic force microscopy.
Conversely, endothelial cell mineralocorticoid receptor deficiency prevented WD
induced diastolic dysfunction, profibrotic, and progrowth signaling, in
conjunction with reductions in macrophage proinflammatory polarization and
improvements in insulin metabolic signaling. Therefore, our findings indicate
that increased endothelial cell mineralocorticoid receptor signaling associated
with consumption of a WD plays a key role in the activation of cardiac
profibrotic, inflammatory, and growth pathways that lead to diastolic dysfunction
in female mice.
PMID- 26441473
TI - The Transition to Adulthood: Life Course Structures and Subjective Perceptions.
AB - We examine the relationships between objective life course structures and the
subjective sense of timing of adult roles and acquisition of adult identity.
Hierarchical latent class analysis is applied to longitudinal data from the Youth
Development Study, describing roles related to school, work, family formation,
and living arrangements from age 17 to 30. The transition to adulthood in this
cohort is well-represented by five pathways probabilistically mapping the timing
and sequencing of these roles and their configurations. Three pathways are
characterized by a school-to-work transition with on-time, delayed, or negligible
family formation. The remaining pathways involve early parenthood with either a
partner and stable full-time work or the lack of a partner and low labor force
attachment. We then show that the subjective sense of timing with respect to
certain adult roles and adult identity acquisition is empirically tied to these
life course structures.
PMID- 26441474
TI - Practical approaches for evaluating adrenal toxicity in nonclinical safety
assessment.
AB - The adrenal gland has characteristic morphological and biochemical features that
render it particularly susceptible to the actions of xenobiotics. As is the case
with other endocrine organs, the adrenal gland is under the control of upstream
organs (hypothalamic-pituitary system) in vivo, often making it difficult to
elucidate the mode of toxicity of a test article. It is very important,
especially for pharmaceuticals, to determine whether a test article-related
change is caused by a direct effect or other associated factors. In addition,
antemortem data, including clinical signs, body weight, food consumption and
clinical pathology, and postmortem data, including gross pathology, organ weight
and histopathologic examination of the adrenal glands and other related organs,
should be carefully monitored and evaluated. During evaluation, the following
should also be taken into account: (1) species, sex and age of animals used, (2)
metabolic activation by a cytochrome P450 enzyme(s) and (3) physicochemical
properties and the metabolic pathway of the test article. In this review, we
describe the following crucial points for toxicologic pathologists to consider
when evaluating adrenal toxicity: functional anatomy, blood supply, hormone
production in each compartment, steroid biosynthesis, potential medulla-cortex
interaction, and species and gender differences in anatomical features and other
features of the adrenal gland which could affect vulnerability to toxic effects.
Finally practical approaches for evaluating adrenal toxicity in nonclinical
safety studies are discussed.
PMID- 26441475
TI - Therapeutic antibodies: their mechanisms of action and the pathological findings
they induce in toxicity studies.
AB - Antibodies can swiftly provide therapeutics to target disease-related molecules
discovered in genomic research. Antibody engineering techniques have been
actively developed and these technological innovations have intensified the
development of therapeutic antibodies. From the mid-1990's, a series of
therapeutic antibodies were launched that are now being used in clinic. The
disease areas that therapeutic antibodies can target have subsequently expanded,
and antibodies are currently utilized as pharmaceuticals for cancer, inflammatory
disease, organ transplantation, cardiovascular disease, infection, respiratory
disease, ophthalmologic disease, and so on. This paper briefly describes the
modes of action of therapeutic antibodies. Several non-clinical study results of
the pathological changes induced by therapeutic antibodies are also presented to
aid the future assessment of the toxic potential of an antibody developed as a
therapeutic.
PMID- 26441476
TI - Evaluation of the teratogenic effects of three traditional Chinese medicines, Si
Jun Zi Tang, Liu Jun Zi Tang and Shenling Baizhu San, during zebrafish pronephros
development.
AB - The aim of this study was to evaluate the teratogenic effects of three common
Chinese medical prescriptions, Si Jun Zi Tang (SJZT), Liu Jun Zi Tang (LJZT) and
Shenling Baizhu San (SLBS), during zebrafish pronephros development. We used the
transgenic zebrafish line Tg(wt1b:EGFP) to assess the teratogenic effects using
12 different protocols, which comprised combinations of 4 doses (0, 25, 250,
1,250 ng/mL) and 3 exposure methods [methods I, 12-36 hours post fertilization
(hpf), II, 24-48 hpf, and III, 24-36 hpf]. As a result, few defects in the
kidneys were observed in the embryos exposed to 25 ng/mL of each medical
prescription. The percentage of kidney malformation phenotypes increased as the
exposure concentrations increased (25 ng/mL, 0-10%; 250 ng/mL, 0-60%; 1,250
ng/mL, 80-100%). Immunohistochemistry for alpha6F, which is a basolateral and
renal tubular differentiation marker, revealed no obvious defective phenotypes in
either SJZT- or LJZT-treated embryos, indicating that these Chinese medical
prescriptions had minimal adverse effects on the pronephric duct. However, SLBS
treated embryos displayed a defective phenotype in the pronephric duct. According
to these findings, we suggest (1) that the Chinese medical prescriptions induced
kidney malformation phenotypes that are dose dependent and (2) that the embryonic
zebrafish kidney was more sensitive to SLBS than SJZT and LJZT.
PMID- 26441477
TI - Comparison of changes in urinary and blood levels of biomarkers associated with
proximal tubular injury in rat models.
AB - To investigate useful biomarkers associated with proximal tubular injury, we
assessed changes in levels of a focused set of biomarkers in urine and blood.
Male rats administered a single dose or four doses of gentamicin (GM, 240
mg/kg/day) or a single dose of cisplatin (CDDP, 5 mg/kg) were euthanized on days
2 (the day after initial dosing) 5, or 12. At each time point, histopathological
examination of the kidney and immunohistochemistry for biomarkers, kidney injury
molecule-1 (Kim-1), lipocalin (NGAL), clusterin (CLU), cystatin C (CysC) and
beta2-microglobulin (beta2M) were performed. Biomarker levels were measured in
urine and blood. In both treatment groups, degenerated/necrotic proximal tubules
and regenerated tubules were mainly observed on days 5 and 12, respectively. At
the same time as these tubular injuries, urinary Kim-1, CysC and beta2M levels
were increased. Moreover, urinary levels of CysC and beta2M in GM-treated animals
and Kim-1 in CDDP-treated animals increased (on day 2) prior to tubular injury on
day 5. This was considered to reflect the characteristics of drug toxicity.
Although almost all of the biomarkers in blood were not sufficiently sensitive to
detect proximal tubular injury, urinary and plasma beta2M levels simultaneously
increased. Therefore, in addition to urinary Kim-1, CysC and beta2M levels,
plasma beta2M levels were also considered useful for detecting proximal tubular
injury.
PMID- 26441478
TI - Histopathology and oxidative stress analysis of concomitant misoprostol and
celecoxib administration.
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective
inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation
associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor
providing decreased gastric injury relative to non-selective NSAIDs, is commonly
prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited
prostaglandin levels. As concomitant celecoxib and misoprostol administration has
been shown to intensify renal adverse effects, this article examined the
influence of concomitant administration on hepatic histopathology, oxidative
stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were
gavaged twice daily (two groups with vehicle and two groups with 100 MUg/kg
misoprostol). From day 3 to day 9, one celecoxib dose (40 mg/kg) replaced a
vehicle dose of one group and one group received celecoxib in addition to
misoprostol. Livers were harvested on day 10. No hepatic abnormalities were
observed denoting a lack of influence by either drug. Also no change in mean
biomarker levels was detected. The changes in hepatic celecoxib concentration in
the misoprostol-receiving group compared to control were not significant. Thus
misoprostol does not influence hepatic celecoxib effects in terms of
histopathology, oxidative stress, or celecoxib concentration level at the dosage
and duration examined.
PMID- 26441479
TI - A spontaneously occurring malignant pituicytoma in a male sprague dawley rat.
AB - Pituicytoma is an extremely rare neoplasm derived from pituicytes, which are
glial cells in the posterior lobe of the pituitary gland. A malignant pituicytoma
was found in the intracranial cavity of a 55-week-old male Sprague-Dawley rat.
Macroscopically, the tumor was located on the sphenoid bone and involved the
pituitary gland. The tumor was composed of sheets of fusiform cells with spindle-
or pleomorphic-shaped nuclei and abundant eosinophilic cytoplasms. The cells were
arranged in a whirling or irregular growth pattern. Some tumor cells were bizarre
multinucleated giant cells with cytoplasmic eosinophilic hyaline droplets. Many
tumor cells were strongly positive for vimentin and glial fibrillary acidic
protein, and some cells were positive for ED-1 and S-100. These findings closely
resembled those of a giant cell glioblastoma derived from the pituitary gland,
suggesting anaplastic pituicytoma. From our review of the literature, we believe
this is the first report of a spontaneous malignant pituicytoma in a rodent.
PMID- 26441480
TI - Spontaneous necrotizing sialometaplasia of the submandibular salivary gland in a
Beagle dog.
AB - A single mass was found on the left submandibular salivary gland at necropsy of a
15-month-old male commercially bred laboratory Beagle dog from a control dose
group from a repeat toxicity study. Microscopically, the mass was composed of a
well-demarcated area of coagulative necrosis surrounded and separated from the
normal salivary gland tissue by a thick fibrovascular capsule. Necrosis was
admixed with areas of hemorrhage, fibrin, edema, fibrinoid necrosis of the
vascular tunica media, and thrombosis of small and large vessels. Within the
necrotic tissue, there was marked ductal hyperplasia, and squamous metaplasia of
duct and acinar epithelium. The mass was diagnosed as necrotizing sialometaplasia
of the submandibular gland. Hyperplastic ductal elements and squamous metaplasia
can be mistaken microscopically with squamous cell carcinoma. Therefore,
pathologists should be aware of this lesion as to avoid errors in the diagnosis
of this benign pathologic condition.
PMID- 26441481
TI - Stakeholder Perceptions of Risk in Construction.
AB - Safety management in construction is an integral effort and its success requires
inputs from all stakeholders across design and construction phases. Effective
risk mitigation relies on the concordance of all stakeholders' risk perceptions.
Many researchers have noticed the discordance of risk perceptions among critical
stakeholders in safe construction work, however few have provided quantifiable
evidence describing them. In an effort to fill this perception gap, this research
performs an experiment that investigates stakeholder perceptions of risk in
construction. Data analysis confirms the existence of such discordance, and
indicates a trend in risk likelihood estimation. With risk perceptions from low
to high, the stakeholders are architects, contractors/safety professionals, and
engineers. Including prior studies, results also suggest that designers have
improved their knowledge in building construction safety, but compared to
builders they present more difficultly in reaching a consensus of perception.
Findings of this research are intended to be used by risk management and decision
makers to reassess stakeholders' varying judgments when considering injury
prevention and hazard assessment.
PMID- 26441482
TI - Spin-labeled small unilamellar vesicles with the T1-sensitive saturation-recovery
EPR display as an oxygen sensitive analyte for measurement of cellular
respiration.
AB - This study validated the use of small unilamellar vesicles (SUVs) made of 1
palmitoyl-2-oleoylphosphatidylcholine with 1 mol% spin label of 1-palmitoyl-2-(16
doxylstearoyl)phosphatidylcholine (16-PC) as an oxygen sensitive analyte to study
cellular respiration. In the analyte the hydrocarbon environment surrounds the
nitroxide moiety of 16-PC. This ensures high oxygen concentration and oxygen
diffusion at the location of the nitroxide as well as isolation of the nitroxide
moiety from cellular reductants and paramagnetic ions that might interfere with
spin-label oximetry measurements. The saturation-recovery EPR approach was
applied in the analysis since this approach is the most direct method to carry
out oximetric studies. It was shown that this display (spin-lattice relaxation
rate) is linear in oxygen partial pressure up to 100% air (159 mmHg). Experiments
using a neuronal cell line in suspension were carried out at X-band for closed
chamber geometry. Oxygen consumption rates showed a linear dependence on the
number of cells. Other significant benefits of the analyte are: the fast
effective rotational diffusion and slow translational diffusion of the spin-probe
is favorable for the measurements, and there is no cross reactivity between
oxygen and paramagnetic ions in the lipid bilayer.
PMID- 26441483
TI - Expression and Function of Hypoxia Inducible Factor-1alpha and Vascular
Endothelial Growth Factor in Pulp Tissue of Teeth under Orthodontic Movement.
AB - Orthodontic force may lead to cell damage, circulatory disturbances, and vascular
changes of the dental pulp, which make a hypoxic environment in pulp. In order to
maintain the homeostasis of dental pulp, hypoxia will inevitably induce the
defensive reaction. However, this is a complex process and is regulated by
numerous factors. In this study, we established an experimental animal model of
orthodontic tooth movement to investigate the effects of mechanical force on the
expression of VEGF and HIF-1alpha in dental pulp. Histological analysis of dental
pulp and expressions of HIF-1alpha and VEGF proteins in dental pulp were
examined. The results showed that inflammation and vascular changes happened in
dental pulp tissue in different periods. Additionally, there were significant
changes in the expression of HIF-1alpha and VEGF proteins under orthodontic
force. After application of mechanical load, expression of HIF-1alpha and VEGF
was markedly positive in 1, 3, 7 d, and 2 w groups, and then it weakened in 4 w
group. These findings suggested that the expression of HIF-1alpha and VEGF was
enhanced by mechanical force. HIF-1alpha and VEGF may play an important role in
retaining the homeostasis of dental pulp during orthodontic tooth movement.
PMID- 26441484
TI - Galactomannan Downregulates the Inflammation Responses in Human Macrophages via
NFkappaB2/p100.
AB - We show that galactomannan, a polysaccharide consisting of a mannose backbone
with galactose side groups present on the cell wall of several fungi, induces a
reprogramming of the inflammatory response in human macrophages through dectin-1
receptor. The nuclear factor kappa-light-chain-enhancer of activated B cells 2
(NFkappaB2)/p100 was overexpressed after galactomannan challenge. Knocking down
NFkappaB2/p100 using small interfering RNA (siRNA) indicated that NFkappaB2/p100
expression is a crucial factor in the progression of the galactomannan-induced
refractoriness. The data presented in this study could be used as a modulator of
inflammatory response in clinical situations where refractory state is required.
PMID- 26441485
TI - Effectiveness of Liraglutide in Type II Diabetes Mellitus Management: Experience
in Emirati Patients.
AB - OBJECTIVE: To measure effectiveness of liraglutide in reducing glycated
hemoglobin (HbA1C), weight, and systolic blood pressure (SBP) in Emirati
patients. DESIGN: A retrospective cohort study. SETTING: Endocrinology clinic in
a 300-bed military hospital. PATIENTS: A total of 152 patients who qualified for
liraglutide between September 21, 2012, (first patient visit) and May 5, 2014
(last patient visit). METHODS: Team collected demographic and clinical data using
a standard form. Data keeper performed univariate analyses to measure the effect
of liraglutide in reducing the three outcomes of interest; namely, HbA1C, weight,
and SBP. RESULTS: One hundred patients had at least the first visit in the clinic
and 98 patients came for a second follow-up visit while on the medication.
Adherence of clinicians to the internal criteria for prescribing liraglutide was
92%. Patients' ages were 47.9 +/- 11.7 years. Male-to-female ratio was almost
1:1. Overall, in the paired analyses, HbA1C decreased from first to second visits
(8.7 +/- 1.9 vs. 7.6 +/- 1.8, P > 0.0001) and remained unchanged in subsequent
visits (eg, in visit 3, HbA1C was 7.4 +/- 1.8). Patients lost an average of 1.3
kg between the first and second visits (99.3 +/- 19.3 vs. 98.0 +/- 19.5, P =
0.0003). The reduction in SBP between visits 1 and 2 was less (130.9 +/- 15.8 vs.
129.9 +/- 16.5, P = 0.5896). ANOVA yielded a significant reduction in HbA1C at 4
months and 6 months (P values < 0.05). SBP dropped by about 3.6 mmHg and weight
by about 2.3 kg (P values > 0.05). CONCLUSIONS: Liraglutide is effective in
reducing HbA1C, weight, and to a lesser extent, SBP in Emirati patients.
PMID- 26441486
TI - Analyzing the Factors Contributing to Withdrawal from Insulin Therapy Following
Additional Administration of Alogliptin: Retrospective Study after Removing
Glucotoxicity with Insulin.
AB - We attempted to examine whether withdrawal from insulin therapy is or is not
possible with administration of additional alogliptin and identify the
contributing factors. The subjects were 43 adult patients with type 2 diabetes
undergoing insulin therapy after admission. After glucotoxicity was removed, 25
mg alogliptin was additionally administered. Insulin was reduced by 15.6 +/- 13.0
units (mean +/- SD), and 17 patients (39.5%) completely withdrew from insulin
therapy. Several factors were compared between the two groups of patients: those
who could withdraw from insulin therapy and those who could not. The former group
showed lower HbA1c levels on admission, a lower insulin dose before adding
alogliptin, lower injection frequencies, and longer treatment histories prior to
admission. Logistic regression analysis showed that lower insulin dose
contributed significantly to withdrawal. These results suggest that a lower
insulin dose is the best predictor for withdrawal from insulin therapy after
adding alogliptin.
PMID- 26441487
TI - Cox Regression Models with Functional Covariates for Survival Data.
AB - We extend the Cox proportional hazards model to cases when the exposure is a
densely sampled functional process, measured at baseline. The fundamental idea is
to combine penalized signal regression with methods developed for mixed effects
proportional hazards models. The model is fit by maximizing the penalized partial
likelihood, with smoothing parameters estimated by a likelihood-based criterion
such as AIC or EPIC. The model may be extended to allow for multiple functional
predictors, time varying coefficients, and missing or unequally-spaced data.
Methods were inspired by and applied to a study of the association between time
to death after hospital discharge and daily measures of disease severity
collected in the intensive care unit, among survivors of acute respiratory
distress syndrome.
PMID- 26441488
TI - Guidelines for the use and interpretation of diagnostic methods in adult food
allergy.
AB - Food allergy has an increasing prevalence in the general population and in Italy
concerns 8 % of people with allergies. The spectrum of its clinical
manifestations ranges from mild symptoms up to potentially fatal anaphylactic
shock. A number of patients can be diagnosed easily by the use of first- and
second-level procedures (history, skin tests and allergen specific IgE). Patients
with complex presentation, such as multiple sensitizations and pollen-food
syndromes, frequently require a third-level approach including molecular
diagnostics, which enables the design of a component-resolved sensitization
profile for each patient. The use of such techniques involves specialists' and
experts' skills on the issue to appropriately meet the diagnostic and therapeutic
needs of patients. Particularly, educational programs for allergists on the use
and interpretation of molecular diagnostics are needed.
PMID- 26441490
TI - Participant report of therapist-delivered active ingredients in a telephone
delivered brief motivational intervention predicts taking steps towards change.
AB - OBJECTIVE: Given the widespread potential for disseminating Motivational
Interviewing (MI) through technology, the question of whether MI active
ingredients are present when not delivered in person is critical to assure high
treatment quality. The Participant Rating Form (PRF) was developed and used to
evaluate therapist-delivered active ingredients in phone-delivered MI with
hazardous drinking Emergency Department patients. METHOD: A factor analysis of
all PRFs completed after receiving one call (n=256) was conducted. Multiple
regression analysis was used to examine whether PRF factors predicted a measure
of motivation to change -- taking steps-at the second call (n=214). RESULTS: The
majority of participants were male (65%), with a mean age of 32 years and with an
average alcohol ASSIST (Alcohol, Smoking, and Substance Involvement Screening
Test) score of 20.5 (SD = 7.1). Results of the factor analysis for the PRF
revealed Relational (working collaboration) and Technical (MI behaviors) factors.
After controlling for demographics, alcohol severity, and baseline readiness, the
technical factor predicted self-report of increased taking steps towards change
while the relational factor did not explain any additional variance. CONCLUSIONS:
Our study adds to the growing literature investigating patient perspectives of
therapist skill as a source of information to better understand MI active
ingredients. The PRF is a feasible instrument for measuring the patient's
experience of phone-based MI. Results indicate that MI active ingredients of
change (relational and technical components) were present in the telephone
intervention as hypothesized. Clinical Trial Registration # 01326169.
PMID- 26441491
TI - Modulation of autonomic activity in neurological conditions: Epilepsy and
Tourette Syndrome.
AB - This manuscript considers the central but neglected role of the autonomic nervous
system in the expression and control of seizures in epilepsy (small) and tics in
Tourette Syndrome (TS). In epilepsy, consideration of autonomic involvement is
typically confined to differential diagnoses (e.g., syncope), or in relation to
Sudden Unexpected Death in Epilepsy (SUDEP). Investigation is more limited in
Tourette Syndrome. The role of the autonomic nervous system in the generation and
prevention of epileptic seizures is largely overlooked. Emotional stimuli such as
anxiety and stress are potent causes of seizures and tic activity in epilepsy and
TS, respectively. This manuscript will describe a possible neural mechanism by
which afferent autonomic projections linked to cognition and behavior influence
central thalamo-cortical regulation, which appears to be an important means for
controlling both seizure and tic activity. It also summarizes the link between
the integrity of the default mode network and autonomic regulation in patients
with epilepsy as well as the link between impaired motor control and autonomic
regulation in patients with TS. Two neurological conditions; epilepsy and TS were
chosen, as seizures and tics represent parameters that can be easily measured to
investigate influences of autonomic functions. The EDA biofeedback approach is
anticipated to gain a strong position within the next generation of treatment for
epilepsy, as a non-invasive technique with minimal side effects. This approach
also takes advantage of the current practical opportunity to utilize growing
digital health technology.
PMID- 26441489
TI - Immunotherapy of Metastatic Colorectal Cancer: Prevailing Challenges and New
Perspectives.
AB - Patients with recurring or metastatic colorectal cancer (mCRC) have strikingly
low long-term survival, while conventional treatments such as chemotherapeutic
intervention and radiation therapy marginally improve longevity. Although, many
factors involving immunosurveillance and immunosuppression were recently
validated as important for patient prognosis and care, a multitude of
experimental immunotherapies designed to combat unresectable mCRC have, in few
cases, successfully mobilized antitumor immune cells against malignancies, nor
conclusively or consistently granted protection, complete remission, and/or
stable disease from immunotherapy - of which benefit less than 10% of those
receiving therapy. After decades of progress, however, new insights into the
mechanisms of immunosuppression, tolerance, and mutation profiling established
novel therapies that circumvent these immunological barriers. This review
underlines the most exciting methods to date that manipulate immune cells to curb
mCRC, including adoptive cell therapy, dendritic cell vaccines, and checkpoint
inhibitor antibodies - of which hint at effective and enduring protection against
disease progression and undetected micrometastases.
PMID- 26441492
TI - The interaction of vision and audition in two-dimensional space.
AB - Using a mouse-driven visual pointer, 10 participants made repeated open-loop
egocentric localizations of memorized visual, auditory, and combined visual
auditory targets projected randomly across the two-dimensional frontal field
(2D). The results are reported in terms of variable error, constant error and
local distortion. The results confirmed that auditory and visual maps of the
egocentric space differ in their precision (variable error) and accuracy
(constant error), both from one another and as a function of eccentricity and
direction within a given modality. These differences were used, in turn, to make
predictions about the precision and accuracy within which spatially and
temporally congruent bimodal visual-auditory targets are localized. Overall, the
improvement in precision for bimodal relative to the best unimodal target
revealed the presence of optimal integration well-predicted by the Maximum
Likelihood Estimation (MLE) model. Conversely, the hypothesis that accuracy in
localizing the bimodal visual-auditory targets would represent a compromise
between auditory and visual performance in favor of the most precise modality was
rejected. Instead, the bimodal accuracy was found to be equivalent to or to
exceed that of the best unimodal condition. Finally, we described how the
different types of errors could be used to identify properties of the internal
representations and coordinate transformations within the central nervous system
(CNS). The results provide some insight into the structure of the underlying
sensorimotor processes employed by the brain and confirm the usefulness of
capitalizing on naturally occurring differences between vision and audition to
better understand their interaction and their contribution to multimodal
perception.
PMID- 26441493
TI - An empirical Bayes normalization method for connectivity metrics in resting state
fMRI.
AB - Functional connectivity analysis using resting-state functional magnetic
resonance imaging (rs-fMRI) has emerged as a powerful technique for investigating
functional brain networks. The functional connectivity is often quantified by
statistical metrics (e.g., Pearson correlation coefficient), which may be
affected by many image acquisition and preprocessing steps such as the head
motion correction and the global signal regression. The appropriate
quantification of the connectivity metrics is essential for meaningful and
reproducible scientific findings. We propose a novel empirical Bayes method to
normalize the functional brain connectivity metrics on a posterior probability
scale. Moreover, the normalization function maps the original connectivity
metrics to values between zero and one, which is well-suited for the graph theory
based network analysis and avoids the information loss due to the (negative
value) hard thresholding step. We apply the normalization method to a simulation
study and the simulation results show that our normalization method effectively
improves the robustness and reliability of the quantification of brain functional
connectivity and provides more powerful group difference (biomarkers) detection.
We illustrate our method on an analysis of a rs-fMRI dataset from the Autism
Brain Imaging Data Exchange (ABIDE) study.
PMID- 26441494
TI - Impaired sense of smell and altered olfactory system in RAG-1(-/-)
immunodeficient mice.
AB - Immune deficiencies are often associated with a number of physical manifestations
including loss of sense of smell and an increased level of anxiety. We have
previously shown that T and B cell-deficient recombinase activating gene (RAG-1)(
/-) knockout mice have an increased level of anxiety-like behavior and altered
gene expression involved in olfaction. In this study, we expanded these findings
by testing the structure and functional development of the olfactory system in
RAG-1 (-/-) mice. Our results show that these mice have a reduced engagement in
different types of odors and this phenotype is associated with disorganized
architecture of glomerular tissue and atrophy of the main olfactory epithelium.
Most intriguingly this defect manifests specifically in adult age and is not due
to impairment in the patterning of the olfactory neuron staining at the embryo
stage. Together these findings provide a formerly unreported biological evidence
for an altered function of the olfactory system in RAG-1 (-/-) mice.
PMID- 26441495
TI - HDAC I inhibition in the dorsal and ventral hippocampus differentially modulates
predator-odor fear learning and generalization.
AB - Although predator odors are ethologically relevant stimuli for rodents, the
molecular pathways and contribution of some brain regions involved in predator
odor conditioning remain elusive. Inhibition of histone deacetylases (HDACs) in
the dorsal hippocampus has been shown to enhance shock-induced contextual fear
learning, but it is unknown if HDACs have differential effects along the dorso
ventral hippocampal axis during predator odor fear learning. We injected MS-275,
a class I HDAC inhibitor, bilaterally in the dorsal or ventral hippocampus of
mice and found that it had no effects on innate anxiety in either region. We then
assessed the effects of MS-275 at different stages of fear learning along the
longitudinal hippocampal axis. Animals were injected with MS-275 or vehicle after
context pre-exposure (pre-conditioning injections), when a representation of the
context is first formed, or after exposure to coyote urine (post-conditioning
injections), when the context becomes associated with predator odor. When MS-275
was administered after context pre-exposure, dorsally injected animals showed
enhanced fear in the training context but were able to discriminate it from a
neutral environment. Conversely, ventrally injected animals did not display
enhanced learning in the training context but generalized the fear response to a
neutral context. However, when MS-275 was administered after conditioning, there
were no differences between the MS-275 and vehicle control groups in either the
dorsal or ventral hippocampus. Surprisingly, all groups displayed generalization
to a neutral context, suggesting that predator odor exposure followed by a mild
stressor such as restraint leads to fear generalization. These results may
elucidate distinct functions of the dorsal and ventral hippocampus in predator
odor-induced fear conditioning as well as some of the molecular mechanisms
underlying fear generalization.
PMID- 26441496
TI - Temporary inactivation of the anterior part of the bed nucleus of the stria
terminalis blocks alarm pheromone-induced defensive behavior in rats.
AB - Rats emit an alarm pheromone in threatening situations. Exposure of rats to this
alarm pheromone induces defensive behaviors, such as head out behavior, and
increases c-Fos expression in brain areas involved in the mediation of defensive
behaviors. One of these brain areas is the anterior bed nucleus of the stria
terminalis (aBNST). The goal of the present study was to investigate if
pharmacological inactivation of the aBNST by local microinjections of the GABAA
receptor-agonist muscimol modulates alarm pheromone-induced defensive behaviors.
We first established the behavioral paradigm of alarm pheromone-induced defensive
behaviors in Sprague-Dawley rats in our laboratory. In a second experiment, we
inactivated the aBNST, then exposed rats to one of four different odors (neck
odor, female urine, alarm pheromone, fox urine) and tested the effects of the
aBNST inactivation on the behavior in response to these odors. Our data show that
temporary inactivation of the aBNST blocked head out behavior in response to the
alarm pheromone. This indicates that the aBNST plays an important role in the
mediation of the alarm pheromone-induced defensive behavior in rats.
PMID- 26441498
TI - A FreeSurfer view of the cortical transcriptome generated from the Allen Human
Brain Atlas.
PMID- 26441497
TI - From UBE3A to Angelman syndrome: a substrate perspective.
AB - Angelman syndrome (AS) is a debilitating neurodevelopmental disorder that is
characterized by motor dysfunction, intellectual disability, speech impairment,
seizures and common features of autism spectrum disorders (ASDs). Some of these
AS related phenotypes can be seen in other neurodevelopmental disorders
(Williams, 2011; Tan et al., 2014). AS patients commonly carry mutations that
render the maternally inherited UBE3A gene non-functional. Duplication of the
chromosomal region containing the UBE3A gene is associated with ASDs. Although
the causative role for UBE3A gene mutations in AS is well established, a long
standing challenge in AS research has been to identify neural substrates of
UBE3A, an E3 ubiquitin ligase. A prevailing hypothesis is that changes in UBE3A
protein levels would alter the levels of a collection of protein substrates,
giving rise to the unique phenotypic aspects of AS and possibly UBE3A associated
ASDs. Interestingly, proteins altered in AS are linked to additional ASDs that
are not previously associated with changes in UBE3A, indicating a possible
molecular overlap underlying the broad-spectrum phenotypes of these neurogenetic
disorders. This idea raises the possibility that there may exist a "one-size-fits
all" approach to the treatment of neurogenetic disorders with phenotypes
overlapping AS. Furthermore, while a comprehensive list of UBE3A substrates and
downstream affected pathways should be developed, this is only part of the story.
The timing of when UBE3A protein functions, through either changes in UBE3A or
possibly substrate expression patterns, appears to be critical for AS phenotype
development. These data call for further investigation of UBE3A substrates and
their timing of action relevant to AS phenotypes.
PMID- 26441499
TI - Methylenedioxypyrovalerone (MDPV) mimics cocaine in its physiological and
behavioral effects but induces distinct changes in NAc glucose.
AB - Methylenedioxypyrovalerone (MDPV) is generally considered to be a more potent
cocaine-like psychostimulant, as it shares a similar pharmacological profile with
cocaine and induces similar physiological and locomotor responses. Recently, we
showed that intravenous cocaine induces rapid rise in nucleus accumbens (NAc)
glucose and established its relation to neural activation triggered by the
peripheral drug actions. This study was conducted to find out whether MDPV, at a
behaviorally equivalent dose, shares a similar pattern of NAc glucose dynamics.
Using enzyme-based glucose sensors coupled with amperometery in freely moving
rats, we found that MDPV tonically decreases NAc glucose levels, a response that
is opposite to what we previously observed with cocaine. By analyzing Skin-Muscle
temperature differentials, a valid measure of skin vascular tone, we found that
MDPV induces vasoconstriction; a similar effect at the level of cerebral vessels
could be responsible for the MDPV-induced decrease in NAc glucose. While cocaine
also induced comparable, if not slightly stronger peripheral vasoconstriction,
this effect was overpowered by local neural activity-induced vasodilation,
resulting in rapid surge in NAc glucose. These results imply that cocaine-users
may be more susceptible to addiction than MDPV-users due to the presence of an
interoceptive signal (i.e., sensory cue), which may result in earlier and more
direct reward detection. Additionally, while health complications arising from
acute cocaine use are typically cardiovascular related, MDPV may be more
dangerous to the brain due to uncompensated cerebral vasoconstriction.
PMID- 26441500
TI - DeID - a data sharing tool for neuroimaging studies.
AB - Funding institutions and researchers increasingly expect that data will be shared
to increase scientific integrity and provide other scientists with the
opportunity to use the data with novel methods that may advance understanding in
a particular field of study. In practice, sharing human subject data can be
complicated because data must be de-identified prior to sharing. Moreover,
integrating varied data types collected in a study can be challenging and time
consuming. For example, sharing data from structural imaging studies of a complex
disorder requires the integration of imaging, demographic and/or behavioral data
in a way that no subject identifiers are included in the de-identified dataset
and with new subject labels or identification values that cannot be tracked back
to the original ones. We have developed a Java program that users can use to
remove identifying information in neuroimaging datasets, while still maintaining
the association among different data types from the same subject for further
studies. This software provides a series of user interaction wizards to allow
users to select data variables to be de-identified, implements functions for
auditing and validation of de-identified data, and enables the user to share the
de-identified data in a single compressed package through various communication
protocols, such as FTPS and SFTP. DeID runs with Windows, Linux, and Mac
operating systems and its open architecture allows it to be easily adapted to
support a broader array of data types, with the goal of facilitating data
sharing. DeID can be obtained at http://www.nitrc.org/projects/deid.
PMID- 26441501
TI - Enhanced functional connectivity involving the ventromedial hypothalamus
following methamphetamine exposure.
AB - Methamphetamine (MA) consumption causes disruption of many biological rhythms
including the sleep-wake cycle. This circadian effect is seen shortly following
MA exposure and later in life following developmental MA exposure. MA phase
shifts, entrains the circadian clock and can also alter the entraining effect of
light by currently unknown mechanisms. We analyzed and compared immunoreactivity
of the immediate early gene c-Fos, a marker of neuronal activity, to assess
neuronal activation 2 h following MA exposure in the light and dark phases. We
used network analyses of correlation patterns derived from global brain
immunoreactivity patterns of c-Fos, to infer functional connectivity between
brain regions. There were five distinct patterns of neuronal activation. In
several brain areas, neuronal activation following exposure to MA was stronger in
the light than the dark phase, highlighting the importance of considering
circadian periods of increased effects of MA in defining experimental conditions
and understanding the mechanisms underlying detrimental effects of MA exposure to
brain function. Functional connectivity between the ventromedial hypothalamus
(VMH) and other brain areas, including the paraventricular nucleus of the
hypothalamus and basolateral and medial amygdala, was enhanced following MA
exposure, suggesting a role for the VMH in the effects of MA on the brain.
PMID- 26441503
TI - Identification of resilient individuals and those at risk for performance
deficits under stress.
AB - Human task performance is affected by exposure to physiological and psychological
stress. The ability to measure the physiological response to stressors and
correlate that to task performance could be used to identify resilient
individuals or those at risk for stress-related performance decrements.
Accomplishing this prior to performance under severe stress or the development of
clinical stress disorders could facilitate focused preparation such as tailoring
training to individual needs. Here we measure the effects of stress on
physiological response and performance through behavior, physiological sensors,
and subjective ratings, and identify which individuals are at risk for stress
related performance decrements. Participants performed military-relevant training
tasks under stress in a virtual environment, with autonomic and hypothalamic
pituitary-adrenal axis (HPA) reactivity analyzed. Self-reported stress, as well
as physiological indices of stress, increased in the group pre-exposed to
socioevaluative stress. Stress response was effectively captured via
electrodermal and cardiovascular measures of heart rate and skin conductance
level. A resilience classification algorithm was developed based upon
physiological reactivity, which correlated with baseline unstressed physiological
and self-reported stress values. Outliers were identified in the experimental
group that had a significant mismatch between self-reported stress and salivary
cortisol. Baseline stress measurements were predictive of individual resilience
to stress, including the impact stress had on physiological reactivity and
performance. Such an approach may have utility in identifying individuals at risk
for problems performing under severe stress. Continuing work has focused on
adapting this method for military personnel, and assessing the utility of various
coping and decision-making strategies on performance and physiological stress.
PMID- 26441504
TI - Editorial: From sex differences in neuroscience to a neuroscience of sex
differences: new directions and perspectives.
PMID- 26441502
TI - An animal model of differential genetic risk for methamphetamine intake.
AB - The question of whether genetic factors contribute to risk for methamphetamine
(MA) use and dependence has not been intensively investigated. Compared to human
populations, genetic animal models offer the advantages of control over genetic
family history and drug exposure. Using selective breeding, we created lines of
mice that differ in genetic risk for voluntary MA intake and identified the
chromosomal addresses of contributory genes. A quantitative trait locus was
identified on chromosome 10 that accounts for more than 50% of the genetic
variance in MA intake in the selected mouse lines. In addition, behavioral and
physiological screening identified differences corresponding with risk for MA
intake that have generated hypotheses that are testable in humans. Heightened
sensitivity to aversive and certain physiological effects of MA, such as MA
induced reduction in body temperature, are hallmarks of mice bred for low MA
intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to
rewarding and reinforcing MA effects, and to MA-induced increases in brain
extracellular dopamine levels. Gene expression analyses implicate the importance
of a network enriched in transcription factor genes, some of which regulate the
mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to
play a role in differential response to MA between the mice bred for high and low
intake. In addition, chromosome 10 candidate gene studies provide strong support
for a trace amine-associated receptor 1 gene, Taar1, polymorphism in risk for MA
intake. MA is a trace amine-associated receptor 1 (TAAR1) agonist, and a non
functional Taar1 allele segregates with high MA consumption. Thus, reduced TAAR1
function has the potential to increase risk for MA use. Overall, existing
findings support the MA drinking lines as a powerful model for identifying
genetic factors involved in determining risk for harmful MA use. Future
directions include the development of a binge model of MA intake, examining the
effect of withdrawal from chronic MA on MA intake, and studying potential Taar1
gene * gene and gene * environment interactions. These and other studies are
intended to improve our genetic model with regard to its translational value to
human addiction.
PMID- 26441505
TI - An array of highly flexible electrodes with a tailored configuration locked by
gelatin during implantation-initial evaluation in cortex cerebri of awake rats.
AB - BACKGROUND: A major challenge in the field of neural interfaces is to overcome
the problem of poor stability of neuronal recordings, which impedes long-term
studies of individual neurons in the brain. Conceivably, unstable recordings
reflect relative movements between electrode and tissue. To address this
challenge, we have developed a new ultra-flexible electrode array and evaluated
its performance in awake non-restrained animals. METHODS: An array of eight
separated gold leads (4 * 10 MUm), individually flexible in 3D, were cut from a
gold sheet using laser milling and insulated with Parylene C. To provide
structural support during implantation into rat cortex, the electrode array was
embedded in a hard gelatin based material, which dissolves after implantation.
Recordings were made during 3 weeks. At termination, the animals were perfused
with fixative and frozen to prevent dislocation of the implanted electrodes. A
thick slice of brain tissue, with the electrode array still in situ, was made
transparent using methyl salicylate to evaluate the conformation of the implanted
electrode array. RESULTS: Median noise levels and signal/noise remained
relatively stable during the 3 week observation period; 4.3-5.9 MUV and 2.8-4.2,
respectively. The spike amplitudes were often quite stable within recording
sessions and for 15% of recordings where single-units were identified, the
highest-SNR unit had an amplitude higher than 150 MUV. In addition, high
correlations (>0.96) between unit waveforms recorded at different time points
were obtained for 58% of the electrode sites. The structure of the electrode
array was well preserved 3 weeks after implantation. CONCLUSIONS: A new
implantable multichannel neural interface, comprising electrodes individually
flexible in 3D that retain its architecture and functionality after implantation
has been developed. Since the new neural interface design is adaptable, it offers
a versatile tool to explore the function of various brain structures.
PMID- 26441506
TI - Emotion, rationality, and decision-making: how to link affective and social
neuroscience with social theory.
AB - In this paper, we argue for a stronger engagement between concepts in affective
and social neuroscience on the one hand, and theories from the fields of
anthropology, economics, political science, and sociology on the other. Affective
and social neuroscience could provide an additional assessment of social
theories. We argue that some of the most influential social theories of the last
four decades-rational choice theory, behavioral economics, and post-structuralism
contain assumptions that are inconsistent with key findings in affective and
social neuroscience. We also show that another approach from the social sciences
plural rationality theory-shows greater compatibility with these findings. We
further claim that, in their turn, social theories can strengthen affective and
social neuroscience. The former can provide more precise formulations of the
social phenomena that neuroscientific models have targeted, can help
neuroscientists who build these models become more aware of their social and
cultural biases, and can even improve the models themselves. To illustrate, we
show how plural rationality theory can be used to further specify and test the
somatic marker hypothesis. Thus, we aim to accelerate the much-needed merger of
social theories with affective and social neuroscience.
PMID- 26441507
TI - Neuroimaging assessment of early and late neurobiological sequelae of traumatic
brain injury: implications for CTE.
AB - Traumatic brain injury (TBI) has been increasingly accepted as a major external
risk factor for neurodegenerative morbidity and mortality. Recent evidence
indicates that the resultant chronic neurobiological sequelae following head
trauma may, at least in part, contribute to a pathologically distinct disease
known as Chronic Traumatic Encephalopathy (CTE). The clinical manifestation of
CTE is variable, but the symptoms of this progressive disease include impaired
memory and cognition, affective disorders (i.e., impulsivity, aggression,
depression, suicidality, etc.), and diminished motor control. Notably, mounting
evidence suggests that the pathology contributing to CTE may be caused by
repetitive exposure to subconcussive hits to the head, even in those with no
history of a clinically evident head injury. Given the millions of athletes and
military personnel with potential exposure to repetitive subconcussive insults
and TBI, CTE represents an important public health issue. However, the incidence
rates and pathological mechanisms are still largely unknown, primarily due to the
fact that there is no in vivo diagnostic tool. The primary objective of this
manuscript is to address this limitation and discuss potential neuroimaging
modalities that may be capable of diagnosing CTE in vivo through the detection of
tau and other known pathological features. Additionally, we will discuss the
challenges of TBI research, outline the known pathology of CTE (with an emphasis
on Tau), review current neuroimaging modalities to assess the potential routes
for in vivo diagnosis, and discuss the future directions of CTE research.
PMID- 26441509
TI - The neuroscience of social conformity: implications for fundamental and applied
research.
AB - The development of closer ties between researchers and practitioners in the
domain of behavior and behavioral change offers useful opportunities for better
informing public policy campaigns via a deeper understanding of the psychological
processes that operate in real-world decision-making. Here, we focus on the
domain of social conformity, and suggest that the recent emergence of laboratory
work using neuroscientific techniques to probe the brain basis of social
influence can prove a useful source of data to better inform models of
conformity. In particular, we argue that this work can have an important role to
play in better understanding the specific mechanisms at work in social
conformity, in both validating and extending current psychological theories of
this process, and in assessing how behavioral change can take place as a result
of exposure to the judgments of others. We conclude by outlining some promising
future directions in this domain, and indicating how this research could
potentially be usefully applied to policy issues.
PMID- 26441508
TI - Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to
social neurocircuits.
AB - Oxytocin and vasopressin are pituitary neuropeptides that have been shown to
affect social processes in mammals. There is growing interest in these molecules
and their receptors as potential precipitants of, and/or treatments for, social
deficits in neurodevelopmental disorders, including autism spectrum disorder.
Numerous behavioral-genetic studies suggest that there is an association between
these peptides and individual social abilities; however, an explanatory model
that links hormonal activity at the receptor level to complex human behavior
remains elusive. The following review summarizes the known associations between
the oxytocin and vasopressin neuropeptide systems and social neurocircuits in the
brain. Following a micro- to macro- level trajectory, current literature on the
synthesis and secretion of these peptides, and the structure, function and
distribution of their respective receptors is first surveyed. Next, current
models regarding the mechanism of action of these peptides on microcircuitry and
other neurotransmitter systems are discussed. Functional neuroimaging evidence on
the acute effects of exogenous administration of these peptides on brain activity
is then reviewed. Overall, a model in which the local neuromodulatory effects of
pituitary neuropeptides on brainstem and basal forebrain regions strengthen
signaling within social neurocircuits proves appealing. However, these findings
are derived from animal models; more research is needed to clarify the relevance
of these mechanisms to human behavior and treatment of social deficits in
neuropsychiatric disorders.
PMID- 26441510
TI - Dopamine D4 receptor gene and religious affiliation correlate with dictator game
altruism in males and not females: evidence for gender-sensitive gene * culture
interaction.
AB - On a large sample of 2288 Han Chinese undergraduates, we investigated how
religion and DRD4 are related to human altruistic giving behavior as measured
with the Andreoni-Miller Dictator Game. This game enables us to clearly specify
(non-)selfishness, efficiency, and fairness motives for sharing. Participants
were further classified into religious categories (Christian, Buddhist-Tao, and
No Religion) based on self-reports, and genotyped for the dopamine D4 receptor
(DRD4) gene exon III VNTR. Our analysis revealed a significant interaction
between religion and DRD4 correlated with giving behavior solely among males:
Whereas no significant association between religion and sharing decisions was
observed in the majority 4R/4R genotype group, a significant difference in giving
behavior between Christian and non-Christian males was seen in the non-4R/4R
group, with Christian men being overall more altruistic (less selfish and fairer)
than non-Christian men. These results support the vantage sensitivity hypothesis
regarding DRD4 that the non-4R/4R "susceptibility" genotype is more responsive to
a positive environment provided by some religions.
PMID- 26441512
TI - Cross-domain processing of musical and vocal emotions in cochlear implant users.
PMID- 26441511
TI - Golgi fragmentation in Alzheimer's disease.
AB - The Golgi apparatus is an essential cellular organelle for post-translational
modifications, sorting, and trafficking of membrane and secretory proteins.
Proper functionality of the Golgi requires the formation of its unique cisternal
stacking morphology. The Golgi structure is disrupted in a variety of
neurodegenerative diseases, suggesting a common mechanism and contribution of
Golgi defects in neurodegenerative disorders. A recent study on Alzheimer's
disease (AD) revealed that phosphorylation of the Golgi stacking protein GRASP65
disrupts its function in Golgi structure formation, resulting in Golgi
fragmentation. Inhibiting GRASP65 phosphorylation restores the Golgi morphology
from Abeta-induced fragmentation and reduces Abeta production. Perturbing Golgi
structure and function in neurons may directly impact trafficking, processing,
and sorting of a variety of proteins essential for synaptic and dendritic
integrity. Therefore, Golgi defects may ultimately promote the development of AD.
In the current review, we focus on the cellular impact of impaired Golgi
morphology and its potential relationship to AD disease development.
PMID- 26441513
TI - NF-kappaB transcription factor role in consolidation and reconsolidation of
persistent memories.
AB - Transcriptional regulation is an important molecular process required for long
term neural plasticity and long-term memory (LTM) formation. Thus, one main
interest in molecular neuroscience in the last decades has been the
identification of transcription factors that are involved in memory processes.
Among them, the nuclear factor kappaB (NF-kappaB) family of transcription factors
has gained interest due to a significant body of evidence that supports a key
role of these proteins in synaptic plasticity and memory. In recent years, the
interest was particularly reinforced because NF-kappaB was characterized as an
important regulator of synaptogenesis. This function may be explained by its
participation in synapse to nucleus communication, as well as a possible local
role at the synapse. This review provides an overview of experimental work
obtained in the last years, showing the essential role of this transcription
factor in memory processes in different learning tasks in mammals. We focus the
review on the consolidation and reconsolidation memory phases as well as on the
regulation of immediate-early and late genes by epigenetic mechanisms that
determine enduring forms of memories.
PMID- 26441515
TI - Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, attenuates
postoperative cognitive dysfunction in aging mice.
AB - Postoperative cognitive dysfunction (POCD) is a recognized clinical entity
characterized with cognitive deficits after anesthesia and surgery, especially in
aged patients. Previous studies have shown that histone acetylation plays a key
role in hippocampal synaptic plasticity and memory formation. However, its role
in POCD remains to be determined. Here, we show that suberoylanilide hydroxamic
acid (SAHA), a histone deacetylase inhibitor, attenuates POCD in aging Mice.
After exposed to the laparotomy, a surgical procedure involving an incision into
abdominal walls to examine the abdominal organs, 16- but not 3-month old male
C57BL/6 mice developed obvious cognitive impairments in the test of long-term
contextual fear conditioning. Intracerebroventricular (i.c.v.) injection of SAHA
at the dose of (20 MUg/2 MUl) 3 h before and daily after the laparotomy restored
the laparotomy-induced reduction of hippocampal acetyl-H3 and acetyl-H4 levels
and significantly attenuated the hippocampus-dependent long-term memory (LTM)
impairments in 16-month old mice. SAHA also reduced the expression of cleaved
caspase-3, inducible nitric oxide synthase (iNOS) and N-methyl-D-aspartate (NMDA)
receptor-calcium/calmodulin dependent kinase II (CaMKII) pathway, and increased
the expression of brain-derived neurotrophic factor (BDNF), synapsin 1, and
postsynaptic density 95 (PSD95). Taken together, our data suggest that the
decrease of histone acetylation contributes to POCD and may serve as a target to
improve the neurological outcome of POCD.
PMID- 26441514
TI - MAG, myelin and overcoming growth inhibition in the CNS.
AB - While neurons in the central nervous system (CNS) have the capacity to regenerate
their axons after injury, they fail to do so, in part because regeneration is
limited by growth inhibitory proteins present in CNS myelin. Myelin-associated
glycoprotein (MAG) was the first myelin-derived growth inhibitory protein
identified, and its inhibitory activity was initially elucidated in 1994
independently by the Filbin lab and the McKerracher lab using cell-based and
biochemical techniques, respectively. Since that time we have gained a wealth of
knowledge concerning the numerous growth inhibitory proteins that are present in
myelin, and we also have dissected many of the neuronal signaling pathways that
act as stop signs for axon regeneration. Here we give an overview of the early
research efforts that led to the identification of myelin-derived growth
inhibitory proteins, and the importance of this family of proteins for
understanding neurotrauma and CNS diseases. We further provide an update on how
this knowledge has been translated towards current clinical studies in
regenerative medicine.
PMID- 26441516
TI - Habituation of glomerular responses in the olfactory bulb following prolonged
odor stimulation reflects reduced peripheral input.
AB - Following prolonged odor stimulation, output from olfactory bulb (OB)
mitral/tufted (M/T) cells is decreased in response to subsequent olfactory
stimulation. Currently, it is unclear if this decrease is a function of
adaptation of peripheral olfactory sensory neuron (OSN) responses or reflects
depression of bulb circuits. We used wide-field calcium imaging in anesthetized
transgenic GCaMP2 mice to compare excitatory glomerular layer odor responses
before and after a 30-s odor stimulation. Significant habituation of subsequent
glomerular odor responses to both the same and structurally similar odorants was
detected with our protocol. To test whether depression of OSN terminals
contributed to this habituation, olfactory nerve layer (ON) stimulation was used
to drive glomerular layer responses in the absence of peripheral odor activation
of the OSNs. Following odor habituation, in contrast to odor-evoked glomerular
responses, ON stimulation-evoked glomerular responses were not habituated. The
difference in response between odor and electrical stimulation following odor
habituation provides evidence that odor response reductions measured in the
glomerular layer of the OB are most likely the result of OSN adaptation processes
taking place in the periphery.
PMID- 26441517
TI - NF-kappaB mediates Gadd45beta expression and DNA demethylation in the hippocampus
during fear memory formation.
AB - Gadd45-mediated DNA demethylation mechanisms have been implicated in the process
of memory formation. However, the transcriptional mechanisms involved in the
regulation of Gadd45 gene expression during memory formation remain unexplored.
NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells)
controls transcription of genes in neurons and is a critical regulator of
synaptic plasticity and memory formation. In silico analysis revealed several NF
kappaB (p65/RelA and cRel) consensus sequences within the Gadd45beta gene
promoter. Whether NF-kappaB activity regulates Gadd45 expression and associated
DNA demethylation in neurons during memory formation is unknown. Here, we found
that learning in a fear conditioning paradigm increased Gadd45beta gene
expression and brain-derivedneurotrophic factor (BDNF) DNA demethylation in area
CA1 of the hippocampus, both of which were prevented with pharmacological
inhibition of NF-kappaB activity. Further experiments found that conditional
mutations in p65/RelA impaired fear memory formation but did not alter changes in
Gadd45beta expression. The learning-induced increases in Gadd45beta mRNA levels,
Gadd45beta binding at the BDNF gene and BDNF DNA demethylation were blocked in
area CA1 of the c-rel knockout mice. Additionally, local siRNA-mediated knockdown
of c-rel in area CA1 prevented fear conditioning-induced increases in Gadd45beta
expression and BDNF DNA demethylation, suggesting that c-Rel containing NF-kappaB
transcription factor complex is responsible for Gadd45beta regulation during
memory formation. Together, these results support a novel transcriptional role
for NF-kappaB in regulation of Gadd45beta expression and DNA demethylation in
hippocampal neurons during fear memory.
PMID- 26441518
TI - Functional characterization of ivermectin binding sites in alpha1beta2gamma2L
GABA(A) receptors.
AB - GABAA receptors (GABAARs) are the major inhibitory neurotransmitter receptors in
the brain and are therapeutic targets for many indications including sedation,
anesthesia and anxiolysis. There is, however, considerable scope for the
development of new therapeutics with improved beneficial effects and reduced side
effect profiles. The anthelminthic drug, ivermectin, activates the GABAAR
although its binding site is not known. The molecular site of action of
ivermectin has, however, been defined by crystallography in the homologous
glutamate-gated chloride channel. Resolving the molecular mechanisms of
ivermectin binding to alpha1beta2gamma2L GABAARs may provide insights into the
design of improved therapeutics. Given that ivermectin binds to subunit
interfaces, we sought to define (1) which subunit interface sites it binds to,
(2) whether these sites are equivalent in terms of ivermectin sensitivity or
efficacy, and (3) how many must be occupied for maximal efficacy. Our approach
involved precluding ivermectin from binding to particular interfaces by
introducing bulky M3 domain 36'F sidechains to the "+" side of those interfaces.
We thereby demonstrated that ivermectin produces irreversible channel activation
only when it binds to the single gamma2L-beta2 interface site. When it binds to
alpha1-beta2 sites it elicits potentiation of GABA-gated currents but has no
irreversible activating effect. Ivermectin cannot bind to the beta2-alpha1
interface site due to its endogenous bulky 36' methionine. Replacing this with an
alanine creates a functional site at this interface, but surprisingly it is
inhibitory. Molecular docking simulations reveal that the gamma2L-beta2 interface
forms more contacts with ivermectin than the other interfaces, possibly
explaining why ivermectin appears to bind irreversibly at this interface. This
study demonstrates unexpectedly stark pharmacological differences among GABAAR
ivermectin binding sites.
PMID- 26441519
TI - Hair cell-type dependent expression of basolateral ion channels shapes response
dynamics in the frog utricle.
AB - The dynamics of vestibular afferent responses are thought to be strongly
influenced by presynaptic properties. In this paper, by performing whole-cell
perforated-patch experiments in the frog utricle, we characterized voltage
dependent currents and voltage responses to current steps and 0.3-100 Hz
sinusoids. Current expression and voltage responses are strongly related to hair
cell type. In particular, voltage responses of extrastriolar type eB (low pass,
3 dB corner at 52.5 +/- 12.8 Hz) and striolar type F cells (resonant, tuned at 60
+/- 46 Hz) agree with the dynamics (tonic and phasic, respectively) of the
afferent fibers they contact. On the other hand, hair cell release (measured with
single-sine membrane DeltaCm measurements) was linearly related to Ca in both
cell types, and therefore did not appear to contribute to dynamics differences.
As a tool for quantifying the relative contribution of basolateral currents and
other presynaptic factors to afferent dynamics, the recorded current, voltage and
release data were used to build a NEURON model of the average extrastriolar type
eB and striolar type F hair cell. The model contained all recorded conductances,
a basic mechanosensitive hair bundle and a ribbon synapse sustained by stochastic
voltage-dependent Ca channels, and could reproduce the recorded hair cell voltage
responses. Simulated release obtained from eB-type and F-type models display
significant differences in dynamics, supporting the idea that basolateral
currents are able to contribute to afferent dynamics; however, release in type eB
and F cell models does not reproduce tonic and phasic dynamics, mainly because of
an excessive phase lag present in both cell types. This suggests the presence in
vestibular hair cells of an additional, phase-advancing mechanism, in cascade
with voltage modulation.
PMID- 26441520
TI - Mechanical stress activates neurites and somata of myenteric neurons.
AB - The particular location of myenteric neurons, sandwiched between the 2 muscle
layers of the gut, implies that their somata and neurites undergo mechanical
stress during gastrointestinal motility. Existence of mechanosensitive enteric
neurons (MEN) is undoubted but many of their basic features remain to be studied.
In this study, we used ultra-fast neuroimaging to record activity of primary
cultured myenteric neurons of guinea pig and human intestine after von Frey hair
evoked deformation of neurites and somata. Independent component analysis was
applied to reconstruct neuronal morphology and follow neuronal signals. Of the
cultured neurons 45% (114 out of 256, 30 guinea pigs) responded to neurite
probing with a burst spike frequency of 13.4 Hz. Action potentials generated at
the stimulation site invaded the soma and other neurites. Mechanosensitive sites
were expressed across large areas of neurites. Many mechanosensitive neurites
appeared to have afferent and efferent functions as those that responded to
deformation also conducted spikes coming from the soma. Mechanosensitive neurites
were also activated by nicotine application. This supported the concept of
multifunctional MEN. 14% of the neurons (13 out of 96, 18 guinea pigs) responded
to soma deformation with burst spike discharge of 17.9 Hz. Firing of MEN adapted
rapidly (RAMEN), slowly (SAMEN), or ultra-slowly (USAMEN). The majority of MEN
showed SAMEN behavior although significantly more RAMEN occurred after neurite
probing. Cultured myenteric neurons from human intestine had similar properties.
Compared to MEN, dorsal root ganglion neurons were activated by neurite but not
by soma deformation with slow adaptation of firing. We demonstrated that MEN
exhibit specific features very likely reflecting adaptation to their specialized
functions in the gut.
PMID- 26441522
TI - Surgery plus anesthesia induces loss of attention in mice.
AB - There is a need to develop animal models to study postoperative delirium.
Inattention is one of the symptoms of delirium. Increases in the levels of alpha
synuclein and S100beta have been reported to be associated with delirium.
Therefore, we set out to determine the effects of surgery plus general anesthesia
on the behavioral changes (including loss of attention) in mice and on the levels
of alpha-synuclein and S100beta in the brain tissues of these mice. C57BL/6J mice
(2- to 8-months-old) had a simple laparotomy plus isoflurane anesthesia. The
behavioral changes, including attention level and the speed of movements, were
determined 12, 24, and 48 h after the surgery plus anesthesia in the mice. The
levels of alpha-synuclein and S100beta in the cortex of these mice following the
surgery plus anesthesia were determined by Western blot analysis. We found that
there was a loss of attention at 24, but not 12 or 48 h following the surgery
plus anesthesia (49% +/- 5 vs. 33% +/- 2.9, P = 0.011, N = 12) in the mice
without significantly affecting the speed of their movements. There were
increases in the levels of total alpha-synuclein (139% +/- 33.5 vs. 100% +/-
13.7, P = 0.037, N = 6) and S100beta (142% +/- 7.7 vs. 100% +/- 6, P = 0.002, N =
6) in the cortex of the mice 12 h following the surgery plus anesthesia. These
findings suggested that the surgery plus isoflurane anesthesia might induce
behavioral and biochemical/cellular changes associated with delirium. We could
use the surgery plus anesthesia in mice to develop an animal model to study
postoperative delirium.
PMID- 26441523
TI - Leptin-dependent neurotoxicity via induction of apoptosis in adult rat neurogenic
cells.
AB - Adipocyte-derived hormone leptin has been recently implicated in the control of
neuronal plasticity. To explore whether modulation of adult neurogenesis may
contribute to leptin control of neuronal plasticity, we used the neurosphere
assay of neural stem cells derived from the adult rat subventricular zone (SVZ).
Endogenous expression of specific leptin receptor (ObRb) transcripts, as revealed
by RT-PCR, is associated with activation of both ERK and STAT-3 pathways via
phosphorylation of the critical ERK/STAT-3 amino acid residues upon addition of
leptin to neurospheres. Furthermore, leptin triggered withdrawal of neural stem
cells from the cell cycle as monitored by Ki67 labeling. This effect was blocked
by pharmacological inhibition of ERK activation thus demonstrating that ERK
mediates leptin effects on neural stem cell expansion. Leptin-dependent
withdrawal of neural stem cells from the cell cycle was associated with increased
apoptosis, as detected by TUNEL, which was preceded by cyclin D1 induction.
Cyclin D1 was indeed extensively colocalized with TUNEL-positive, apoptotic
nuclei. Cyclin-D1 silencing by specific shRNA prevented leptin-induced decrease
of the cell number per neurosphere thus pointing to the causal relationship
between leptin actions on apoptosis and cyclin D1 induction. Leptin target cells
in SVZ neurospheres were identified by double TUNEL/phenotypic marker
immunocytofluorescence as differentiating neurons mostly. The inhibition of
neural stem cell expansion via ERK/cyclin D1-triggered apoptosis defines novel
biological action of leptin which may be involved in adiposity-dependent
neurotoxicity.
PMID- 26441524
TI - Clock and clock-controlled genes are differently expressed in the retina, lamina
and in selected cells of the visual system of Drosophila melanogaster.
AB - The retina and the first optic neuropil (lamina) of Drosophila show circadian
rhythms in various processes. To learn about the regulation of circadian rhythms
in the retina and lamina and in two cell types, glial and the lamina L2
interneurons, we examined expression of the following clock genes; per, tim, clk,
and cry and clock-controlled genes (ccgs); Atpalpha, nrv2, brp, Pdfr. We found
that the expression of gene studied is specific for the retina and lamina. The
rhythms of per and tim expression in the retina and glial cells are similar to
that observed in the whole head and in clock neurons, while they differ in the
lamina and L2 cells. In both the retina and lamina, CRY seems to be a repressor
of clk expression. In L2 interneurons per expression is not cyclic indicating the
other function of PER in those cells than in the circadian molecular clock. In
contrast to per and tim, the pattern of clk and cry expression is similar in both
the retina and lamina. The retina holds the autonomous oscillators but the
expression of cry and ccgs, Atpalpha and nrv2, is also regulated by inputs from
the pacemaker transmitted by PDF and ITP neuropeptides.
PMID- 26441521
TI - Neurodegeneration and microtubule dynamics: death by a thousand cuts.
AB - Microtubules form important cytoskeletal structures that play a role in
establishing and maintaining neuronal polarity, regulating neuronal morphology,
transporting cargo, and scaffolding signaling molecules to form signaling hubs.
Within a neuronal cell, microtubules are found to have variable lengths and can
be both stable and dynamic. Microtubule associated proteins, post-translational
modifications of tubulin subunits, microtubule severing enzymes, and signaling
molecules are all known to influence both stable and dynamic pools of
microtubules. Microtubule dynamics, the process of interconversion between stable
and dynamic pools, and the proportions of these two pools have the potential to
influence a wide variety of cellular processes. Reduced microtubule stability has
been observed in several neurodegenerative diseases such as Alzheimer's disease
(AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and
tauopathies like Progressive Supranuclear Palsy. Hyperstable microtubules, as
seen in Hereditary Spastic Paraplegia (HSP), also lead to neurodegeneration.
Therefore, the ratio of stable and dynamic microtubules is likely to be important
for neuronal function and perturbation in microtubule dynamics might contribute
to disease progression.
PMID- 26441525
TI - Breaking boundaries-coagulation and fibrinolysis at the neurovascular interface.
AB - Blood proteins at the neurovascular unit (NVU) are emerging as important
molecular determinants of communication between the brain and the immune system.
Over the past two decades, roles for the plasminogen activation (PA)/plasmin
system in fibrinolysis have been extended from peripheral dissolution of blood
clots to the regulation of central nervous system (CNS) functions in physiology
and disease. In this review, we discuss how fibrin and its proteolytic
degradation affect neuroinflammatory, degenerative and repair processes. In
particular, we focus on novel functions of fibrin-the final product of the
coagulation cascade and the main substrate of plasmin-in the activation of immune
responses and trafficking of immune cells into the brain. We also comment on the
suitability of the coagulation and fibrinolytic systems as potential biomarkers
and drug targets in diseases, such as multiple sclerosis (MS), Alzheimer's
disease (AD) and stroke. Studying coagulation and fibrinolysis as major molecular
pathways that regulate cellular functions at the NVU has the potential to lead to
the development of novel strategies for the detection and treatment of neurologic
diseases.
PMID- 26441526
TI - Potentials and limits to enhance cognitive functions in healthy and pathological
aging by tDCS.
AB - Transcranial direct current stimulation (tDCS) is a non-invasive brain
stimulation technique that is increasingly used in research and clinical settings
to enhance the effects of cognitive training. In our present review, we will
first summarize studies using tDCS alone and in combination with cognitive
training in older adults and patients with Alzheimer's dementia (AD). We will
also review one study (Meinzer et al., 2014c) that showed an improvement in
cognitive performance during anodal tDCS over the left inferior frontal cortex in
patients with mild cognitive impairment (MCI) which is regarded as a prodromal
stage of AD. Although promising short-term results have been reported, evidence
from randomized controlled trials (RCTs) with sufficient sample sizes is scarce.
In addition, stimulation protocols (in terms of intensity, duration, and
repetition of stimulation) that lead to sustained improvements in outcome
measures relevant for daily life still remain to be established. Following, we
will discuss modulating factors such as technical parameters as well as the
question whether there are specific cognitive functions (e.g., learning, memory
consolidation, executive control) which are more amenable to tDCS enhancement
than others. Finally, we will highlight future directions and limitations in this
field and emphasize the need to conduct RCTs to establish efficacy of
interventions for activities of daily life for a given patient population.
PMID- 26441527
TI - Editorial: The role of glia in plasticity and behavior.
PMID- 26441529
TI - Editorial: Progenitor diversity and neural cell specification in the central
nervous system.
PMID- 26441528
TI - Systematic Review of the Neurobiological Relevance of Chemokines to Psychiatric
Disorders.
AB - Psychiatric disorders are highly prevalent and disabling conditions of increasing
public health relevance. Much recent research has focused on the role of
cytokines in the pathophysiology of psychiatric disorders; however, the related
family of immune proteins designated chemokines has been relatively neglected.
Chemokines were originally identified as having chemotactic function on immune
cells; however, recent evidence has begun to elucidate novel, brain-specific
functions of these proteins of relevance to the mechanisms of psychiatric
disorders. A systematic review of both human and animal literature in the PubMed
and Google Scholar databases was undertaken. After application of all inclusion
and exclusion criteria, 157 references were remained for the review. Some early
mechanistic evidence does associate select chemokines with the neurobiological
processes, including neurogenesis, modulation of the neuroinflammatory response,
regulation of the hypothalamus-pituitary-adrenal axis, and modulation of
neurotransmitter systems. This early evidence however does not clearly
demonstrate any specificity for a certain psychiatric disorder, but is primarily
relevant to mechanisms which are shared across disorders. Notable exceptions
include CCL11 that has recently been shown to impair hippocampal function in
aging - of distinct relevance to Alzheimer's disease and depression in the
elderly, and pre-natal exposure to CXCL8 that may disrupt early
neurodevelopmental periods predisposing to schizophrenia. Pro-inflammatory
chemokines, such as CCL2, CCL7, CCL8, CCL12, and CCL13, have been shown to drive
chemotaxis of pro-inflammatory cells to the inflamed or injured CNS. Likewise,
CX3CL has been implicated in promoting glial cells activation, pro-inflammatory
cytokines secretion, expression of ICAM-1, and recruitment of CD4+ T-cells into
the CNS during neuroinflammatory processes. With further translational research,
chemokines may present novel diagnostic and/or therapeutic targets in psychiatric
disorders.
PMID- 26441530
TI - Quantifying mechanical force in axonal growth and guidance.
AB - Mechanical force plays a fundamental role in neuronal development, physiology,
and regeneration. In particular, research has shown that force is involved in
growth cone-mediated axonal growth and guidance as well as stretch-induced
elongation when an organism increases in size after forming initial synaptic
connections. However, much of the details about the exact role of force in these
fundamental processes remain unknown. In this review, we highlight: (1) standing
questions concerning the role of mechanical force in axonal growth and guidance;
and (2) different experimental techniques used to quantify forces in axons and
growth cones. We believe that satisfying answers to these questions will require
quantitative information about the relationship between elongation, forces,
cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and
stiffness contributing to directional growth advance. Furthermore, we address why
a wide range of force values have been reported in the literature, and what these
values mean in the context of neuronal mechanics. We hope that this review will
provide a guide for those interested in studying the role of force in development
and regeneration of neuronal networks.
PMID- 26441531
TI - Expression and function of Neuregulin 1 and its signaling system ERBB2/3 in the
enteric nervous system.
AB - Neuregulin 1 (NRG1) is suggested to promote the survival and maintenance of the
enteric nervous system (ENS). As deficiency in its corresponding receptor
signaling complex ERBB2/ERBB3 leads to postnatal colonic hypo/aganglionosis we
assessed the distributional and expressional pattern of the NRG1-ERBB2/ERBB3
system in the human colon and explored the neurotrophic capacity of NRG1 on
cultured enteric neurons. Site-specific mRNA expression of the NRG1-ERBB2/3
system was determined in microdissected samples harvested from enteric
musculature and ganglia. Localization of NRG1, ERBB2 and ERBB3 was determined by
dual-label-immunohistochemistry using pan-neuronal and pan-glial markers.
Morphometric analysis was performed on NRG1-stimulated rat enteric nerve cultures
to evaluate neurotrophic effects. mRNA expression of the NRG1-ERBB2/3 system was
determined by qPCR. Co-localization of NRG1 with neuronal or synaptic markers was
analyzed in enteric nerve cultures stimulated with glial cell line-derived
neurotrophic factor (GDNF). The NRG1 system was expressed in both neurons and
glial cells of enteric ganglia and in nerve fibers. NRG1 significantly enhanced
growth parameters in enteric nerve cell cultures and ErB3 mRNA expression was
down-regulated upon NRG1 stimulation. GDNF negatively regulates ErbB2 and ErbB3
mRNA expression. The NRG1-ERBB2/3 system is physiologically present in the human
ENS and NRG1 acts as a neurotrophic factor for the ENS. The down-regulation of
ErbB3/ErbB2 in GDNF stimulated nerve cell cultures points to an interaction of
both neurotrophic factors. Thus, the data may provide a basis to assess disturbed
signaling components of the NRG1 system in enteric neuropathies.
PMID- 26441532
TI - Activated regulatory T cell regulates neural stem cell proliferation in the
subventricular zone of normal and ischemic mouse brain through interleukin 10.
AB - Recent studies have demonstrated that the depletion of Regulatory T cells (Tregs)
inhibits neural progenitor cell migration after brain ischemia. However, whether
Tregs affect neural stem/progenitor cell proliferation is unclear. We explored
the effect of Tregs on neurogenesis in the subventricular zone (SVZ) after
ischemia. Tregs were isolated and activated in vitro. Adult male C57BL/6 mice
underwent 60 min transient middle cerebral artery occlusion (tMCAO). Then Tregs
(1 * 10(5)) were injected into the left lateral ventricle (LV) of normal and
ischemic mouse brain. Neurogenesis was determined by immunostaining. The
mechanism was examined by inhibiting interleukin 10 (IL-10) and transforming
growth factor (TGF-beta) signaling. We found that the number of BrdU(+) cells in
the SVZ was significantly increased in the activated Tregs-treated mice. Double
immunostaining showed that these BrdU(+) cells expressed Mash1. Blocking IL-10
reduced the number of Mash1(+)/BrdU(+) cells, but increased the amount of
GFAP(+)/BrdU(+) cells. Here, we conclude that activated Tregs enhanced neural
stem cell (NSC) proliferation in the SVZ of normal and ischemic mice; blockage of
IL-10 abolished Tregs-mediated NSC proliferation in vivo and in vitro. Our
results suggest that activated Tregs promoted NSC proliferation via IL-10, which
provides a new therapeutic approach for ischemic stroke.
PMID- 26441533
TI - Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression
and function in hippocampal CA1 neurons.
AB - Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during
birth and can lead to long-term epilepsy and cognitive deficits. In a rodent
hypoxic seizure (HS) model, we have previously demonstrated a critical role for
seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in
epileptogenesis and cognitive consequences, in part due to GluA maturational
upregulation of expression. Similarly, as the expression and function of the N
Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also
developmentally controlled, we examined how early life seizures during the
critical period of synaptogenesis could modify GluN development and function. In
a postnatal day (P)10 rat model of neonatal seizures, we found that seizures
could alter GluN2/3 subunit composition of GluNs and physiological function of
synaptic GluNs. In hippocampal slices removed from rats within 48-96 h following
seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic
currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs
showed a decreased sensitivity to GluN2B selective antagonists and decreased
Mg(2+) sensitivity at negative holding potentials, indicating a higher proportion
of GluN2A and GluN3A subunit function, respectively. These physiological findings
were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A
protein. These results suggest that altered GluN function and expression could
potentially contribute to future epileptogenesis following neonatal seizures, and
may represent potential therapeutic targets for the blockade of future
epileptogenesis in the developing brain.
PMID- 26441534
TI - Microglia mechanics: immune activation alters traction forces and durotaxis.
AB - Microglial cells are key players in the primary immune response of the central
nervous system. They are highly active and motile cells that chemically and
mechanically interact with their environment. While the impact of chemical
signaling on microglia function has been studied in much detail, the current
understanding of mechanical signaling is very limited. When cultured on compliant
substrates, primary microglial cells adapted their spread area, morphology, and
actin cytoskeleton to the stiffness of their environment. Traction force
microscopy revealed that forces exerted by microglia increase with substrate
stiffness until reaching a plateau at a shear modulus of ~5 kPa. When cultured on
substrates incorporating stiffness gradients, microglia preferentially migrated
toward stiffer regions, a process termed durotaxis. Lipopolysaccharide-induced
immune-activation of microglia led to changes in traction forces, increased
migration velocities and an amplification of durotaxis. We finally developed a
mathematical model connecting traction forces with the durotactic behavior of
migrating microglial cells. Our results demonstrate that microglia are
susceptible to mechanical signals, which could be important during central
nervous system development and pathologies. Stiffness gradients in tissue
surrounding neural implants such as electrodes, for example, could mechanically
attract microglial cells, thus facilitating foreign body reactions detrimental to
electrode functioning.
PMID- 26441535
TI - ProNGF derived from rat sciatic nerves downregulates neurite elongation and axon
specification in PC12 cells.
AB - Several reports have shown that a sciatic nerve conditioned media (CM) causes
neuronal-like differentiation in PC12 cells. This differentiation is featured by
neurite outgrowth, which are exclusively dendrites, without axon or sodium
current induction. In previous studies, our group reported that the CM
supplemented with a generic inhibitor for tyrosine kinase receptors (k252a)
enhanced the CM-induced morphological differentiation upregulating neurite
outgrowth, axonal formation and sodium current elicitation. Sodium currents were
also induced by depletion of endogenous precursor of nerve growth factorr
(proNGF) from the CM (pNGFd-CM). Given that sodium currents, neurite outgrowth
and axon specification are important features of neuronal differentiation, in the
current manuscript, first we investigated if proNGF was hindering the full PC12
cell neuronal-like differentiation. Second, we studied the effects of exogenous
wild type (pNGFwt) and mutated (pNGFmut) proNGF isoforms over sodium currents and
whether or not their addition to the pNGFd-CM would prevent sodium current
elicitation. Third, we investigated if proNGF was exerting its negative
regulation through the sortilin receptor, and for this, the proNGF action was
blocked with neurotensin (NT), a factor known to compete with proNGF for
sortilin. Thereby, here we show that pNGFd-CM enhanced cell differentiation, cell
proportion with long neurites, total neurite length, induced axonal formation and
sodium current elicitation. Interestingly, treatment of PC12 cells with wild type
or mutated proNGF isoforms elicited sodium currents. Supplementing pNGFd-CM with
pNGFmut reduced 35% the sodium currents. On the other hand, pNGFd-CM+pNGFwt
induced larger sodium currents than pNGFd-CM. Finally, treatments with CM
supplemented with NT showed that sortilin was mediating proNGF negative
regulation, since its blocking induced similar effects than the pNGFd-CM
treatment. Altogether, our results suggest that proNGF within the CM, is one of
the main inhibitors of full neuronal differentiation, acting through sortilin
receptor.
PMID- 26441538
TI - Tracking the activity-dependent diffusion of synaptic proteins using restricted
photoconversion of Dendra2.
AB - Spines are small protrusions on dendritic membranes receiving inputs from axonal
termini. They consist in a head connected to the dendritic shaft by a narrow neck
and contain multiple synaptic proteins that interact in a coordinated manner to
allow for synaptic communication. This process involves many proteins that are
moving in and out spines. However, comparing this synaptodendritic movement in
basal and stimulated conditions is very challenging. Here we describe an elegant
method to measure the activity-dependent diffusion of synaptic proteins using
Dendra2 photoconversion. We provide a successful method to obtain Dendra2
photoconverted images and a step-by-step procedure to analyze the data. This live
imaging approach may also apply to investigate the diffusion of proteins across
other subcellular compartments or organelles including but not restricted to,
nucleus, nucleolus, ER, or vesicular structures. Once the imaging system is set
up, data can be acquired in 1-30 min and analyzed in approximately 1-4 h.
PMID- 26441537
TI - CD36 is involved in oleic acid detection by the murine olfactory system.
AB - Olfactory signals influence food intake in a variety of species. To maximize the
chances of finding a source of calories, an animal's preference for fatty foods
and triglycerides already becomes apparent during olfactory food search behavior.
However, the molecular identity of both receptors and ligands mediating olfactory
dependent fatty acid recognition are, so far, undescribed. We here describe that
a subset of olfactory sensory neurons expresses the fatty acid receptor CD36 and
demonstrate a receptor-like localization of CD36 in olfactory cilia by STED
microscopy. CD36-positive olfactory neurons share olfaction-specific transduction
elements and project to numerous glomeruli in the ventral olfactory bulb. In
accordance with the described roles of CD36 as fatty acid receptor or co-receptor
in other sensory systems, the number of olfactory neurons responding to oleic
acid, a major milk component, in Ca(2+) imaging experiments is drastically
reduced in young CD36 knock-out mice. Strikingly, we also observe marked age
dependent changes in CD36 localization, which is prominently present in the
ciliary compartment only during the suckling period. Our results support the
involvement of CD36 in fatty acid detection by the mammalian olfactory system.
PMID- 26441536
TI - The aged brain: genesis and fate of residual progenitor cells in the
subventricular zone.
AB - Neural stem cells (NSCs) persist in the adult mammalian brain through life. The
subventricular zone (SVZ) is the largest source of stem cells in the nervous
system, and continuously generates new neuronal and glial cells involved in brain
regeneration. During aging, the germinal potential of the SVZ suffers a
widespread decline, but the causes of this turn down are not fully understood.
This review provides a compilation of the current knowledge about the age-related
changes in the NSC population, as well as the fate of the newly generated cells
in the aged brain. It is known that the neurogenic capacity is clearly disrupted
during aging, while the production of oligodendroglial cells is not compromised.
Interestingly, the human brain seems to primarily preserve the ability to produce
new oligodendrocytes instead of neurons, which could be related to the
development of neurological disorders. Further studies in this matter are
required to improve our understanding and the current strategies for fighting
neurological diseases associated with senescence.
PMID- 26441539
TI - Neto2-null mice have impaired GABAergic inhibition and are susceptible to
seizures.
AB - Neto2 is a transmembrane protein that interacts with the neuron-specific K(+)-Cl(
) cotransporter (KCC2) in the central nervous system (CNS). Efficient KCC2
transport is essential for setting the neuronal Cl(-) gradient, which is required
for fast GABAergic inhibition. Neto2 is required to maintain the normal abundance
of KCC2 in neurons, and increases KCC2 function by binding to the active
oligomeric form of this cotransporter. In the present study, we characterized
GABAergic inhibition and KCC2-mediated neuronal chloride homeostasis in pyramidal
neurons from adult hippocampal slices. Using gramicidin perforated patch clamp
recordings we found that the reversal potential for GABA (EGABA) was
significantly depolarized. We also observed that surface levels of KCC2 and
phosphorylation of KCC2 serine 940 (Ser940) were reduced in Neto2(-/-) neurons
compared to wild-type controls. To examine GABAergic inhibition we recorded
spontaneous inhibitory postsynaptic currents (sIPSCs) and found that Neto2(-/-)
neurons had significant reductions in both their amplitude and frequency. Based
on the critical role of Neto2 in regulating GABAergic inhibition we rationalized
that Neto2-null mice would be prone to seizure activity. We found that Neto2-null
mice demonstrated a decrease in the latency to pentylenetetrazole (PTZ)-induced
seizures and an increase in seizure severity.
PMID- 26441540
TI - Proteolytic regulation of synaptic plasticity in the mouse primary visual cortex:
analysis of matrix metalloproteinase 9 deficient mice.
AB - The extracellular matrix (ECM) is known to play important roles in regulating
neuronal recovery from injury. The ECM can also impact physiological synaptic
plasticity, although this process is less well understood. To understand the
impact of the ECM on synaptic function and remodeling in vivo, we examined ECM
composition and proteolysis in a well-established model of experience-dependent
plasticity in the visual cortex. We describe a rapid change in ECM protein
composition during Ocular Dominance Plasticity (ODP) in adolescent mice, and a
loss of ECM remodeling in mice that lack the extracellular protease, matrix
metalloproteinase-9 (MMP9). Loss of MMP9 also attenuated functional ODP following
monocular deprivation (MD) and reduced excitatory synapse density and spine
density in sensory cortex. While we observed no change in the morphology of
existing dendritic spines, spine dynamics were altered, and MMP9 knock-out (KO)
mice showed increased turnover of dendritic spines over a period of 2 days. We
also analyzed the effects of MMP9 loss on microglia, as these cells are involved
in extracellular remodeling and have been recently shown to be important for
synaptic plasticity. MMP9 KO mice exhibited very limited changes in microglial
morphology. Ultrastructural analysis, however, showed that the extracellular
space surrounding microglia was increased, with concomitant increases in
microglial inclusions, suggesting possible changes in microglial function in the
absence of MMP9. Taken together, our results show that MMP9 contributes to ECM
degradation, synaptic dynamics and sensory-evoked plasticity in the mouse visual
cortex.
PMID- 26441541
TI - Cell-type specific modulation of neocortical UP and DOWN states.
PMID- 26441542
TI - Development and regulation of chloride homeostasis in the central nervous system.
AB - gamma-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter of the
mature central nervous system (CNS). The developmental switch of GABAergic
transmission from excitation to inhibition is induced by changes in Cl(-)
gradients, which are generated by cation-Cl(-) co-transporters. An accumulation
of Cl(-) by the Na(+)-K(+)-2Cl(-) co-transporter (NKCC1) increases the
intracellular Cl(-) concentration ([Cl(-)]i) such that GABA depolarizes neuronal
precursors and immature neurons. The subsequent ontogenetic switch, i.e.,
upregulation of the Cl(-)-extruder KCC2, which is a neuron-specific K(+)-Cl(-) co
transporter, with or without downregulation of NKCC1, results in low [Cl(-)]i
levels and the hyperpolarizing action of GABA in mature neurons. Development of
Cl(-) homeostasis depends on developmental changes in NKCC1 and KCC2 expression.
Generally, developmental shifts (decreases) in [Cl(-)]i parallel the maturation
of the nervous system, e.g., early in the spinal cord, hypothalamus and thalamus,
followed by the limbic system, and last in the neocortex. There are several
regulators of KCC2 and/or NKCC1 expression, including brain-derived neurotrophic
factor (BDNF), insulin-like growth factor (IGF), and cystic fibrosis
transmembrane conductance regulator (CFTR). Therefore, regionally different
expression of these regulators may also contribute to the regional developmental
shifts of Cl(-) homeostasis. KCC2 and NKCC1 functions are also regulated by
phosphorylation by enzymes such as PKC, Src-family tyrosine kinases, and WNK1-4
and their downstream effectors STE20/SPS1-related proline/alanine-rich kinase
(SPAK)-oxidative stress responsive kinase-1 (OSR1). In addition, activation of
these kinases is modulated by humoral factors such as estrogen and taurine.
Because these transporters use the electrochemical driving force of Na(+) and
K(+) ions, topographical interaction with the Na(+)-K(+) ATPase and its
modulators such as creatine kinase (CK) should modulate functions of Cl(-)
transporters. Therefore, regional developmental regulation of these regulators
and modulators of Cl(-) transporters may also play a pivotal role in the
development of Cl(-) homeostasis.
PMID- 26441543
TI - Dual processing of sulfated steroids in the olfactory system of an anuran
amphibian.
AB - Chemical communication is widespread in amphibians, but if compared to later
diverging tetrapods the available functional data is limited. The existing
information on the vomeronasal system of anurans is particularly sparse.
Amphibians represent a transitional stage in the evolution of the olfactory
system. Most species have anatomically separated main and vomeronasal systems,
but recent studies have shown that in anurans their molecular separation is still
underway. Sulfated steroids function as migratory pheromones in lamprey and have
recently been identified as natural vomeronasal stimuli in rodents. Here we
identified sulfated steroids as the first known class of vomeronasal stimuli in
the amphibian Xenopus laevis. We show that sulfated steroids are detected and
concurrently processed by the two distinct olfactory subsystems of larval Xenopus
laevis, the main olfactory system and the vomeronasal system. Our data revealed a
similar but partially different processing of steroid-induced responses in the
two systems. Differences of detection thresholds suggest that the two information
channels are not just redundant, but rather signal different information.
Furthermore, we found that larval and adult animals excrete multiple sulfated
compounds with physical properties consistent with sulfated steroids. Breeding
tadpole and frog water including these compounds activated a large subset of
sensory neurons that also responded to synthetic steroids, showing that sulfated
steroids are likely to convey intraspecific information. Our findings indicate
that sulfated steroids are conserved vomeronasal stimuli functioning in
phylogenetically distant classes of tetrapods living in aquatic and terrestrial
habitats.
PMID- 26441544
TI - Bi-frontal transcranial alternating current stimulation in the ripple range
reduced overnight forgetting.
AB - High frequency oscillations in the hippocampal structures recorded during sleep
have been proved to be essential for long-term episodic memory consolidation in
both animals and in humans. The aim of this study was to test if transcranial
Alternating Current Stimulation (tACS) of the dorsolateral prefrontal cortex
(DLPFC) in the hippocampal ripple range, applied bi-frontally during encoding,
could modulate declarative memory performance, measured immediately after
encoding, and after a night's sleep. An associative word-pair learning test was
used. During an evening encoding phase, participants received 1 mA 140 Hz tACS or
sham stimulation over both DLPFCs for 10 min while being presented twice with a
list of word-pairs. Cued recall performance was investigated 10 min after
training and the morning following the training session. Forgetting from evening
to morning was observed in the sham condition, but not in the 140 Hz stimulation
condition. 140 Hz tACS during encoding may have an effect on the consolidation of
declarative material.
PMID- 26441545
TI - Bypassing hazard of housekeeping genes: their evaluation in rat granule neurons
treated with cerebrospinal fluid of multiple sclerosis subjects.
AB - Gene expression studies employing real-time PCR has become an intrinsic part of
biomedical research. Appropriate normalization of target gene transcript(s) based
on stably expressed housekeeping genes is crucial in individual experimental
conditions to obtain accurate results. In multiple sclerosis (MS), several gene
expression studies have been undertaken, however, the suitability of housekeeping
genes to express stably in this disease is not yet explored. Recent research
suggests that their expression level may vary under different experimental
conditions. Hence it is indispensible to evaluate their expression stability to
accurately normalize target gene transcripts. The present study aims to evaluate
the expression stability of seven housekeeping genes in rat granule neurons
treated with cerebrospinal fluid of MS patients. The selected reference genes
were quantified by real time PCR and their expression stability was assessed
using GeNorm and NormFinder algorithms. GeNorm identified transferrin receptor
(Tfrc) and microglobulin beta-2 (B2m) the most stable genes followed by ribosomal
protein L19 (Rpl19) whereas beta-actin (ActB) and glyceraldehyde-3-phosphate
dehydrogenase (Gapdh) the most fluctuated ones in these neurons. NormFinder
identified Tfrc as the best invariable gene followed by B2m and Rpl19. ActB and
Gapdh were the least stable genes as analyzed by NormFinder algorithm. Both
methods reported Tfrc and B2m the most stably expressed genes and Gapdh the least
stable one. Altogether our data demonstrate the significance of pre-validation of
housekeeping genes for accurate normalization and indicates Tfrc and B2m as best
endogenous controls in MS. ActB and Gapdh are not recommended in gene expression
studies related to current one.
PMID- 26441546
TI - A new measure for the strength of electrical synapses.
AB - Electrical synapses, like chemical synapses, mediate intraneuronal communication.
Electrical synapses are typically quantified by subthreshold measurements of
coupling, which fall short in describing their impact on spiking activity in
coupled neighbors. Here, we describe a novel measurement for electrical synapse
strength that directly evaluates the effect of synaptically transmitted activity
on spike timing. This method, also applicable to neurotransmitter-based synapses,
communicates the considerable strength of electrical synapses. For electrical
synapses measured in rodent slices of the thalamic reticular nucleus and in
simple model neurons, spike timing is modulated by tens of ms by activity in a
coupled neighbor.
PMID- 26441548
TI - The olfactory thalamus: unanswered questions about the role of the mediodorsal
thalamic nucleus in olfaction.
AB - The mediodorsal thalamic nucleus (MDT) is a higher order thalamic nucleus and its
role in cognition is increasingly well established. Interestingly, components of
the MDT also have a somewhat unique sensory function as they link primary
olfactory cortex to orbitofrontal associative cortex. In fact, anatomical
evidence firmly demonstrates that the MDT receives direct input from primary
olfactory areas including the piriform cortex and has dense reciprocal
connections with the orbitofrontal cortex. The functions of this olfactory
pathway have been poorly explored but lesion, imaging, and electrophysiological
studies suggest that these connections may be involved in olfactory processing
including odor perception, discrimination, learning, and attention. However, many
important questions regarding the MDT and olfaction remain unanswered. Our goal
here is not only to briefly review the existing literature but also to highlight
some of the remaining questions that need to be answered to better define the
role(s) of the MDT in olfactory processing.
PMID- 26441547
TI - Spatial diversity of spontaneous activity in the cortex.
AB - The neocortex is a layered sheet across which a basic organization is thought to
widely apply. The variety of spontaneous activity patterns is similar throughout
the cortex, consistent with the notion of a basic cortical organization. However,
the basic organization is only an outline which needs adjustments and additions
to account for the structural and functional diversity across cortical layers and
areas. Such diversity suggests that spontaneous activity is spatially diverse in
any particular behavioral state. Accordingly, this review summarizes the laminar
and areal diversity in cortical activity during fixation and slow oscillations,
and the effects of attention, anesthesia and plasticity on the cortical
distribution of spontaneous activity. Among questions that remain open,
characterizing the spatial diversity in spontaneous membrane potential may help
elucidate how differences in circuitry among cortical regions supports their
varied functions. More work is also needed to understand whether cortical
spontaneous activity not only reflects cortical circuitry, but also contributes
to determining the outcome of plasticity, so that it is itself a factor shaping
the functional diversity of the cortex.
PMID- 26441549
TI - Efficient population coding of naturalistic whisker motion in the ventro
posterior medial thalamus based on precise spike timing.
AB - The rodent whisker-associated thalamic nucleus (VPM) contains a somatotopic map
where whisker representation is divided into distinct neuronal sub-populations,
called "barreloids". Each barreloid projects to its associated cortical barrel
column and so forms a gateway for incoming sensory stimuli to the barrel cortex.
We aimed to determine how the population of neurons within one barreloid encodes
naturalistic whisker motion. In rats, we recorded the extracellular activity of
up to nine single neurons within a single barreloid, by implanting silicon probes
parallel to the longitudinal axis of the barreloids. We found that play-back of
texture-induced whisker motion evoked sparse responses, timed with millisecond
precision. At the population level, there was synchronous activity: however,
different subsets of neurons were synchronously active at different times. Mutual
information between population responses and whisker motion increased near
linearly with population size. When normalized to factor out firing rate
differences, we found that texture was encoded with greater informational
efficiency than white noise. These results indicate that, within each VPM
barreloid, there is a rich and efficient population code for naturalistic whisker
motion based on precisely timed, population spike patterns.
PMID- 26441551
TI - Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie
lateralized language function in the human brain.
AB - The arcuate fasciculus (AF) in the human brain has asymmetric structural
properties. However, the topographic organization of the asymmetric AF
projections to the cortex and its relevance to cortical function remain unclear.
Here we mapped the posterior projections of the human AF in the inferior parietal
and lateral temporal cortices using surface-based structural connectivity
analysis based on diffusion MRI and investigated their hemispheric differences.
We then performed the cross-modal comparison with functional connectivity based
on resting-state functional MRI (fMRI) and task-related cortical activation based
on fMRI using a semantic classification task of single words. Structural
connectivity analysis showed that the left AF connecting to Broca's area
predominantly projected in the lateral temporal cortex extending from the
posterior superior temporal gyrus to the mid part of the superior temporal sulcus
and the middle temporal gyrus, whereas the right AF connecting to the right
homolog of Broca's area predominantly projected to the inferior parietal cortex
extending from the mid part of the supramarginal gyrus to the anterior part of
the angular gyrus. The left-lateralized projection regions of the AF in the left
temporal cortex had asymmetric functional connectivity with Broca's area,
indicating structure-function concordance through the AF. During the language
task, left-lateralized cortical activation was observed. Among them, the brain
responses in the temporal cortex and Broca's area that were connected through the
left-lateralized AF pathway were specifically correlated across subjects. These
results suggest that the human left AF, which structurally and functionally
connects the mid temporal cortex and Broca's area in asymmetrical fashion,
coordinates the cortical activity in these remote cortices during a semantic
decision task. The unique feature of the left AF is discussed in the context of
the human capacity for language.
PMID- 26441552
TI - A clearer view of the insect brain-combining bleaching with standard whole-mount
immunocytochemistry allows confocal imaging of pigment-covered brain areas for 3D
reconstruction.
AB - In the study of insect neuroanatomy, three-dimensional (3D) reconstructions of
neurons and neuropils have become a standard technique. As images have to be
obtained from whole-mount brain preparations, pigmentation on the brain surface
poses a serious challenge to imaging. In insects, this is a major problematic in
the first visual neuropil of the optic lobe, the lamina, which is obstructed by
the pigment of the retina as well as by the pigmented fenestration layer. This
has prevented inclusion of this major processing center of the insect visual
system into most neuroanatomical brain atlases and hinders imaging of neurons
within the lamina by confocal microscopy. It has recently been shown that
hydrogen peroxide bleaching is compatible with immunohistochemical labeling in
insect brains, and we therefore developed a simple technique for removal of
pigments on the surface of insect brains by chemical bleaching. We show that our
technique enables imaging of the pigment-obstructed regions of insect brains when
combined with standard protocols for both anti-synapsin-labeled as well as
neurobiotin-injected samples. This method can be combined with different fixation
procedures, as well as different fluorophore excitation wavelengths without
negative effects on staining quality. It can therefore serve as an effective
addition to most standard histology protocols used in insect neuroanatomy.
PMID- 26441553
TI - Heterogeneous generation of new cells in the adult echinoderm nervous system.
AB - Adult neurogenesis, generation of new functional cells in the mature central
nervous system (CNS), has been documented in a number of diverse organisms,
ranging from humans to invertebrates. However, the origin and evolution of this
phenomenon is still poorly understood for many of the key phylogenetic groups.
Echinoderms are one such phylum, positioned as a sister group to chordates within
the monophyletic clade Deuterostomia. They are well known for the ability of
their adult organs, including the CNS, to completely regenerate after injury.
Nothing is known, however, about production of new cells in the nervous tissue
under normal physiological conditions in these animals. In this study, we show
that new cells are continuously generated in the mature radial nerve cord (RNC)
of the sea cucumber Holothuria glaberrima. Importantly, this neurogenic activity
is not evenly distributed, but is significantly more extensive in the lateral
regions of the RNC than along the midline. Some of the new cells generated in the
apical region of the ectoneural neuroepithelium leave their place of origin and
migrate basally to populate the neural parenchyma. Gene expression analysis
showed that generation of new cells in the adult sea cucumber CNS is associated
with transcriptional activity of genes known to be involved in regulation of
various aspects of neurogenesis in other animals. Further analysis of one of
those genes, the transcription factor Myc, showed that it is expressed, in some,
but not all radial glial cells, suggesting heterogeneity of this CNS progenitor
cell population in echinoderms.
PMID- 26441550
TI - Morphological changes of glutamatergic synapses in animal models of Parkinson's
disease.
AB - The striatum and the subthalamic nucleus (STN) are the main entry doors for
extrinsic inputs to reach the basal ganglia (BG) circuitry. The cerebral cortex,
thalamus and brainstem are the key sources of glutamatergic inputs to these
nuclei. There is anatomical, functional and neurochemical evidence that
glutamatergic neurotransmission is altered in the striatum and STN of animal
models of Parkinson's disease (PD) and that these changes may contribute to
aberrant network neuronal activity in the BG-thalamocortical circuitry.
Postmortem studies of animal models and PD patients have revealed significant
pathology of glutamatergic synapses, dendritic spines and microcircuits in the
striatum of parkinsonians. More recent findings have also demonstrated a
significant breakdown of the glutamatergic corticosubthalamic system in
parkinsonian monkeys. In this review, we will discuss evidence for synaptic
glutamatergic dysfunction and pathology of cortical and thalamic inputs to the
striatum and STN in models of PD. The potential functional implication of these
alterations on synaptic integration, processing and transmission of extrinsic
information through the BG circuits will be considered. Finally, the significance
of these pathological changes in the pathophysiology of motor and non-motor
symptoms in PD will be examined.
PMID- 26441555
TI - Editorial: Parkinson's disease: cell vulnerability and disease progression.
PMID- 26441554
TI - Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus.
AB - Cholecystokinin (CCK)- and parvalbumin (PV)-expressing neurons constitute the two
major populations of perisomatic GABAergic neurons in the cortex and the
hippocampus. As CCK- and PV-GABA neurons differ in an array of morphological,
biochemical and electrophysiological features, it has been proposed that they
form distinct inhibitory ensembles which differentially contribute to network
oscillations and behavior. However, the relationship and balance between CCK- and
PV-GABA neurons in the inhibitory networks of the brain is currently unclear as
the distribution of these cells has never been compared on a large scale. Here,
we systemically investigated the distribution of CCK- and PV-GABA cells across a
wide number of discrete forebrain regions using an intersectional genetic
approach. Our analysis revealed several novel trends in the distribution of these
cells. While PV-GABA cells were more abundant overall, CCK-GABA cells outnumbered
PV-GABA cells in several subregions of the hippocampus, medial prefrontal cortex
and ventrolateral temporal cortex. Interestingly, CCK-GABA cells were relatively
more abundant in secondary/association areas of the cortex (V2, S2, M2, and
AudD/AudV) than they were in corresponding primary areas (V1, S1, M1, and Aud1).
The reverse trend was observed for PV-GABA cells. Our findings suggest that the
balance between CCK- and PV-GABA cells in a given cortical region is related to
the type of processing that area performs; inhibitory networks in the secondary
cortex tend to favor the inclusion of CCK-GABA cells more than networks in the
primary cortex. The intersectional genetic labeling approach employed in the
current study expands upon the ability to study molecularly defined subsets of
GABAergic neurons. This technique can be applied to the investigation of
neuropathologies which involve disruptions to the GABAergic system, including
schizophrenia, stress, maternal immune activation and autism.
PMID- 26441557
TI - Editorial: Individual differences: from neurobiological bases to new insight on
approach and avoidance behavior.
PMID- 26441556
TI - Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the
human pons.
AB - Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects.
In rodents, NPS is expressed in a few pontine cell clusters. Its receptor (NPSR1)
is, however, widely distributed in the brain. The anxiolytic and arousal
promoting effects of NPS make the NPS-NPSR1 system an interesting potential drug
target in mood-related disorders. However, so far possible disease-related
mechanisms involving NPS have only been studied in rodents. To validate the
relevance of these animal studies for i.a. drug development, we have explored the
distribution of NPS-expressing neurons in the human pons using in situ
hybridization and stereological methods and we compared the distribution of NPS
mRNA expressing neurons in the human and rat brain. The calculation revealed a
total number of 22,317 +/- 2411 NPS mRNA-positive neurons in human, bilaterally.
The majority of cells (84%) were located in the parabrachial area in human: in
the extension of the medial and lateral parabrachial nuclei, in the Kolliker-Fuse
nucleus and around the adjacent lateral lemniscus. In human, in sharp contrast to
the rodents, only very few NPS-positive cells (5%) were found close to the locus
coeruleus. In addition, we identified a smaller cell cluster (11% of all NPS
cells) in the pontine central gray matter both in human and rat, which has not
been described previously even in rodents. We also examined the distribution of
NPSR1 mRNA-expressing neurons in the human pons. These cells were mainly located
in the rostral laterodorsal tegmental nucleus, the cuneiform nucleus, the
microcellular tegmental nucleus region and in the periaqueductal gray. Our
results show that both NPS and NPSR1 in the human pons are preferentially
localized in regions of importance for integration of visceral autonomic
information and emotional behavior. The reported interspecies differences must,
however, be considered when looking for targets for new pharmacotherapeutical
interventions.
PMID- 26441558
TI - BASCO: a toolbox for task-related functional connectivity.
AB - BASCO (BetA Series COrrelation) is a user-friendly MATLAB toolbox with a
graphical user interface (GUI) which allows investigating functional connectivity
in event-related functional magnetic resonance imaging (fMRI) data. Connectivity
analyses extend and compliment univariate activation analyses since the actual
interaction between brain regions involved in a task can be explored. BASCO
supports seed-based functional connectivity as well as brain network analyses.
Although there are a multitude of advanced toolboxes for investigating resting
state functional connectivity, BASCO is the first toolbox for evaluating task
related whole-brain functional connectivity employing a large number of network
nodes. Thus, BASCO allows investigating task-specific rather than resting-state
networks. Here, we summarize the main features of the toolbox and describe the
methods and algorithms.
PMID- 26441559
TI - Effect of saccade automaticity on perisaccadic space compression.
AB - Briefly presented stimuli occurring just before or during a saccadic eye movement
are mislocalized, leading to a compression of visual space toward the target of
the saccade. In most cases this has been measured in subjects over-trained to
perform a stereotyped and unnatural task where saccades are repeatedly driven to
the same location, marked by a highly salient abrupt onset. Here, we asked to
what extent the pattern of perisaccadic mislocalization depends on this specific
context. We addressed this question by studying perisaccadic localization in a
set of participants with no prior experience in eye-movement research, measuring
localization performance as they practiced the saccade task. Localization was
marginally affected by practice over the course of the experiment and it was
indistinguishable from the performance of expert observers. The mislocalization
also remained similar when the expert observers were tested in a condition
leading to less stereotypical saccadic behavior-with no abrupt onset marking the
saccade target location. These results indicate that perisaccadic compression is
a robust behavior, insensitive to the specific paradigm used to drive saccades
and to the level of practice with the saccade task.
PMID- 26441560
TI - Superior memorizers employ different neural networks for encoding and recall.
AB - Superior memorizers often employ the method of loci (MoL) to memorize large
amounts of information. The MoL, known since ancient times, relies on a complex
process where information to be memorized is bound to landmarks along mental
routes in a previously memorized environment. However, functional magnetic
resonance imaging data on groups of trained superior memorizer are rare. Based on
the memorizing strategy reported by superior memorizers, we developed a scheme of
the processes successively employed during memorizing and recalling digits and
relate these to brain activation that is specific for the encoding and recall
period. In the examined superior memorizers several regions, suggested to be
involved in mental navigation and digit-to-word processing, were specifically
activated during encoding: bilateral early visual cortex, retrosplenial cortex,
left parahippocampus, left visual cortex, and left superior parietal cortex.
Although the scheme suggests that some steps during encoding and recall seem to
be analog, none of the encoding areas were specifically activated during the
recall. Instead, we found strong activation in left anterior superior temporal
gyrus, which we relate to recalling the sequential order of the digits, and right
motor cortex that may be related to reciting the digits.
PMID- 26441561
TI - Enhancing astronaut performance using sensorimotor adaptability training.
AB - Astronauts experience disturbances in balance and gait function when they return
to Earth. The highly plastic human brain enables individuals to modify their
behavior to match the prevailing environment. Subjects participating in specially
designed variable sensory challenge training programs can enhance their ability
to rapidly adapt to novel sensory situations. This is useful in our application
because we aim to train astronauts to rapidly formulate effective strategies to
cope with the balance and locomotor challenges associated with new gravitational
environments-enhancing their ability to "learn to learn." We do this by coupling
various combinations of sensorimotor challenges with treadmill walking. A unique
training system has been developed that is comprised of a treadmill mounted on a
motion base to produce movement of the support surface during walking. This
system provides challenges to gait stability. Additional sensory variation and
challenge are imposed with a virtual visual scene that presents subjects with
various combinations of discordant visual information during treadmill walking.
This experience allows them to practice resolving challenging and conflicting
novel sensory information to improve their ability to adapt rapidly. Information
obtained from this work will inform the design of the next generation of
sensorimotor countermeasures for astronauts.
PMID- 26441562
TI - Distinguishing cognitive state with multifractal complexity of hippocampal
interspike interval sequences.
AB - Fractality, represented as self-similar repeating patterns, is ubiquitous in
nature and the brain. Dynamic patterns of hippocampal spike trains are known to
exhibit multifractal properties during working memory processing; however, it is
unclear whether the multifractal properties inherent to hippocampal spike trains
reflect active cognitive processing. To examine this possibility, hippocampal
neuronal ensembles were recorded from rats before, during and after a spatial
working memory task following administration of tetrahydrocannabinol (THC), a
memory-impairing component of cannabis. Multifractal detrended fluctuation
analysis was performed on hippocampal interspike interval sequences to determine
characteristics of monofractal long-range temporal correlations (LRTCs),
quantified by the Hurst exponent, and the degree/magnitude of multifractal
complexity, quantified by the width of the singularity spectrum. Our results
demonstrate that multifractal firing patterns of hippocampal spike trains are a
marker of functional memory processing, as they are more complex during the
working memory task and significantly reduced following administration of memory
impairing THC doses. Conversely, LRTCs are largest during resting state
recordings, therefore reflecting different information compared to
multifractality. In order to deepen conceptual understanding of multifractal
complexity and LRTCs, these measures were compared to classical methods using
hippocampal frequency content and firing variability measures. These results
showed that LRTCs, multifractality, and theta rhythm represent independent
processes, while delta rhythm correlated with multifractality. Taken together,
these results provide a novel perspective on memory function by demonstrating
that the multifractal nature of spike trains reflects hippocampal microcircuit
activity that can be used to detect and quantify cognitive, physiological, and
pathological states.
PMID- 26441563
TI - NeuroControl of movement: system identification approach for clinical benefit.
AB - Progress in diagnosis and treatment of movement disorders after neurological
diseases like stroke, cerebral palsy (CP), dystonia and at old age requires
understanding of the altered capacity to adequately respond to physical obstacles
in the environment. With posture and movement disorders, the control of muscles
is hampered, resulting in aberrant force generation and improper impedance
regulation. Understanding of this improper regulation not only requires the
understanding of the role of the neural controller, but also attention for: (1)
the interaction between the neural controller and the "plant", comprising the
biomechanical properties of the musculaskeletal system including the viscoelastic
properties of the contractile (muscle) and non-contractile (connective) tissues:
neuromechanics; and (2) the closed loop nature of neural controller and
biomechanical system in which cause and effect interact and are hence difficult
to separate. Properties of the neural controller and the biomechanical system
need to be addressed synchronously by the combination of haptic robotics, (closed
loop) system identification (SI), and neuro-mechanical modeling. In this paper,
we argue that assessment of neuromechanics in response to well defined
environmental conditions and tasks may provide for key parameters to understand
posture and movement disorders in neurological diseases and for biomarkers to
increase accuracy of prediction models for functional outcome and effects of
intervention.
PMID- 26441565
TI - Spontaneous movement tempo can be influenced by combining action observation and
somatosensory stimulation.
AB - Spontaneous movement tempo (SMT) was a popular field of study of the Gestalt
psychologists It can be determined from subjects freely tapping out a rhythm with
their finger, and it has been found to average about 2 Hz. A previous study
showed that SMT changed after the observation of rhythmical movements performed
at frequency different from the SMT. This effect was long-lasting only when
movement execution immediately followed action observation (AO). We recently
demonstrated that only when AO was combined with peripheral nerve stimulation (AO
PNS) was it possible to induce plastic changes in the excitability of the motor
cortex, whereas AO and PNS alone did not evoke any changes. Here we investigated
whether the observation of rhythmical actions at a frequency higher than the SMT
combined with PNS induced lasting changes in SMT even in absence of immediate
movement execution. Forty-eight participants were assigned to four groups. In AO
PNS group they observed a video showing a right hand performing a finger
opposition movement sequence at 3 Hz and contemporarily received an electrical
stimulation at the median nerve; in AO group and PNS group participants either
observed the same video or received the same electrical stimulation of the AO-PNS
group, respectively; in LANDSCAPE group subjects observed a neutral video.
Participants performed a finger opposition movement sequence at spontaneous
movement rate before and 30 min after the conditioning protocols. Results showed
that SMT significantly changed only after AO-PNS. This result suggested that the
AO-PNS protocol was able to induce lasting changes in SMT due to neuroplasticity
mechanisms, indicating possible application of AO-PNS in rehabilitative
treatments.
PMID- 26441564
TI - Motion perception: a review of developmental changes and the role of early visual
experience.
AB - Significant controversies have arisen over the developmental trajectory for the
perception of global motion. Studies diverge on the age at which it becomes adult
like, with estimates ranging from as young as 3 years to as old as 16. In this
article, we review these apparently conflicting results and suggest a potentially
unifying hypothesis that may also account for the contradictory literature in
neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). We also
discuss the extent to which patterned visual input during this period is
necessary for the later development of motion perception. We conclude by
addressing recent studies directly comparing different types of motion
integration, both in typical and atypical development, and suggest areas ripe for
future research.
PMID- 26441566
TI - Building an adaptive brain across development: targets for neurorehabilitation
must begin in infancy.
AB - Much progress has been made toward behavioral and pharmacological intervention in
intellectual disability, which was once thought too difficult to treat. Down
syndrome (DS) research has shown rapid advances, and clinical trials are
currently underway, with more on the horizon. Here, we review the literature on
the emergent profile of cognitive development in DS, emphasizing that treatment
approaches must consider how some "end state" impairments, such as language
deficits, may develop from early alterations in neural systems beginning in
infancy. Specifically, we highlight evidence suggesting that there are pre- and
early postnatal alterations in brain structure and function in DS, resulting in
disturbed network function across development. We stress that these early
alterations are likely amplified by Alzheimer's disease (AD) progression and poor
sleep. Focusing on three network hubs (prefrontal cortex, hippocampus, and
cerebellum), we discuss how these regions may relate to evolving deficits in
cognitive function in individuals with DS, and to their language profile in
particular.
PMID- 26441568
TI - Motor imagery reinforces brain compensation of reach-to-grasp movement after
cervical spinal cord injury.
AB - Individuals with cervical spinal cord injury (SCI) that causes tetraplegia are
challenged with dramatic sensorimotor deficits. However, certain rehabilitation
techniques may significantly enhance their autonomy by restoring reach-to-grasp
movements. Among others, evidence of motor imagery (MI) benefits for neurological
rehabilitation of upper limb movements is growing. This literature review
addresses MI effectiveness during reach-to-grasp rehabilitation after
tetraplegia. Among articles from MEDLINE published between 1966 and 2015, we
selected ten studies including 34 participants with C4 to C7 tetraplegia and 22
healthy controls published during the last 15 years. We found that MI of possible
non-paralyzed movements improved reach-to-grasp performance by: (i) increasing
both tenodesis grasp capabilities and muscle strength; (ii) decreasing movement
time (MT), and trajectory variability; and (iii) reducing the abnormally
increased brain activity. MI can also strengthen motor commands by potentiating
recruitment and synchronization of motoneurons, which leads to improved recovery.
These improvements reflect brain adaptations induced by MI. Furthermore, MI can
be used to control brain-computer interfaces (BCI) that successfully restore
grasp capabilities. These results highlight the growing interest for MI and its
potential to recover functional grasping in individuals with tetraplegia, and
motivate the need for further studies to substantiate it.
PMID- 26441569
TI - Physical attractiveness and sex as modulatory factors of empathic brain responses
to pain.
AB - Empathy is a process that comprises affective sharing, imagining, and
understanding the emotions and mental states of others. The brain structures
involved in empathy for physical pain include the anterior insula (AI), and the
anterior cingulate cortex (ACC). High empathy may lead people to undertake pro
social behavior. It is important to understand how this process can be changed,
and what factors these empathic responses depend on. Physical attractiveness is a
major social and evolutional cue, playing a role in the formation of
interpersonal evaluation. The aim of the study was to determine how
attractiveness affects the level of empathy both in relation to self-rated
behavior and in terms of activation of specific empathy-related brain regions.
Twenty-seven subjects (14 female and 13 male) were studied using functional
magnetic resonance imaging (fMRI) method while they were watching short video
scenes involving physically more and less attractive men and women who exhibited
pain responses. In the absence of behavioral effects in compassion ratings, we
observed stronger activation in empathic brain structures (ACC; AI) for less
attractive men and for attractive women than for attractive men. Evolutionary
psychology studies suggest that beauty is valued more highly in females than
males, which might lead observers to empathize more strongly with the attractive
woman than the men. Attractive mens' faces are typically associated with enhanced
masculine facial characteristics and are considered to possess fewer desirable
personality traits compared with feminized faces. This could explain why more
empathy was shown to less attractive men. In conclusion, the study showed that
the attractiveness and sex of a model are important modulators of empathy for
pain.
PMID- 26441567
TI - Non-mammalian models in behavioral neuroscience: consequences for biological
psychiatry.
AB - Current models in biological psychiatry focus on a handful of model species, and
the majority of work relies on data generated in rodents. However, in the same
sense that a comparative approach to neuroanatomy allows for the identification
of patterns of brain organization, the inclusion of other species and an adoption
of comparative viewpoints in behavioral neuroscience could also lead to increases
in knowledge relevant to biological psychiatry. Specifically, this approach could
help to identify conserved features of brain structure and behavior, as well as
to understand how variation in gene expression or developmental trajectories
relates to variation in brain and behavior pertinent to psychiatric disorders. To
achieve this goal, the current focus on mammalian species must be expanded to
include other species, including non-mammalian taxa. In this article, we review
behavioral neuroscientific experiments in non-mammalian species, including
traditional "model organisms" (zebrafish and Drosophila) as well as in other
species which can be used as "reference." The application of these domains in
biological psychiatry and their translational relevance is considered.
PMID- 26441570
TI - The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep
phenotyping of Alzheimer's disease biomarkers in down syndrome.
AB - To gain further knowledge on the preclinical phase of Alzheimer's disease (AD),
we sought to characterize cognitive performance, neuroimaging and plasma-based AD
biomarkers in a cohort of non-demented adults with down syndrome (DS). The goal
of the down syndrome biomarker Initiative (DSBI) pilot is to test feasibility of
this approach for future multicenter studies. We enrolled 12 non-demented
participants with DS between the ages of 30-60 years old. Participants underwent
extensive cognitive testing, volumetric MRI, amyloid positron emission tomography
(PET; 18F-florbetapir), fluorodeoxyglucose (FDG) PET (18F-fluorodeoxyglucose) and
retinal amyloid imaging. In addition, plasma beta-amyloid (Abeta) species were
measured and Apolipoprotein E (ApoE) genotyping was performed. Results from our
multimodal analysis suggest greater hippocampal atrophy with amyloid load.
Additionally, we identified an inverse relationship between amyloid load and
regional glucose metabolism. Cognitive and functional measures did not correlate
with amyloid load in DS but did correlate with regional FDG PET measures.
Biomarkers of AD can be readily studied in adults with DS as in other preclinical
AD populations. Importantly, all subjects in this feasibility study were able to
complete all test procedures. The data indicate that a large, multicenter
longitudinal study is feasible to better understand the trajectories of AD
biomarkers in this enriched population. This trial is registered with
ClinicalTrials.gov, number NCT02141971.
PMID- 26441571
TI - The translational study of apathy-an ecological approach.
AB - Apathy, a quantitative reduction in goal-directed behavior, is a prevalent
symptom dimension with a negative impact on functional outcome in various
neuropsychiatric disorders including schizophrenia and depression. The aim of
this review is to show that interview-based assessment of apathy in humans and
observation of spontaneous rodent behavior in an ecological setting can serve as
an important complementary approach to already existing task-based assessment, to
study and understand the neurobiological bases of apathy. We first discuss the
paucity of current translational approaches regarding animal equivalents of
psychopathological assessment of apathy. We then present the existing evaluation
scales for the assessment of apathy in humans and propose five sub-domains of
apathy, namely self-care, social interaction, exploration, work/education and
recreation. Each of the items in apathy evaluation scales can be assigned to one
of these sub-domains. We then show that corresponding, well-validated behavioral
readouts exist for rodents and that, indeed, three of the five human apathy sub
domains have a rodent equivalent. In conclusion, the translational ecological
study of apathy in humans and rodents is possible and will constitute an
important approach to increase the understanding of the neurobiological bases of
apathy and the development of novel treatments.
PMID- 26441572
TI - Normal Neurochemistry in the Prefrontal and Cerebellar Brain of Adults with
Attention-Deficit Hyperactivity Disorder.
AB - Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental
disorder. In an attempt to extend earlier neurochemical findings, we organized a
magnetic resonance spectroscopy (MRS) study as part of a large, government
funded, prospective, randomized, multicenter clinical trial comparing the
effectiveness of specific psychotherapy with counseling and stimulant treatment
with placebo treatment (Comparison of Methylphenidate and Psychotherapy Study).
We report the baseline neurochemical data for the anterior cingulate cortex (ACC)
and the cerebellum in a case-control setting. For the trial, 1,480 adult patients
were contacted for participation, 518 were assessed for eligibility, 433 were
randomized, and 187 were potentially eligible for neuroimaging. The control group
included 119 healthy volunteers. Single-voxel proton MRS was performed. In the
patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria
for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar
spectra in the control group. We did not find any significant neurometabolic
differences between the ADHD and control group in the ACC (Wilks' lambda test: p
= 0.97) or in the cerebellum (p = 0.62). Thus, we were unable to replicate
earlier findings in this methodologically sophisticated study. We discuss our
findings in the context of a comprehensive review of other MRS studies on ADHD
and a somewhat skeptical neuropsychiatric research perspective. As in other
neuropsychiatric disorders, the unclear nosological status of ADHD might be an
explanation for false-negative findings.
PMID- 26441573
TI - A shared neural network for emotional expression and perception: an anatomical
study in the macaque monkey.
AB - Over the past two decades, the insula has been described as the sensory
"interoceptive cortex". As a consequence, human brain imaging studies have
focused on its role in the sensory perception of emotions. However, evidence from
neurophysiological studies in non-human primates have shown that the insula is
also involved in generating emotional and communicative facial expressions. In
particular, a recent study demonstrated that electrical stimulation of the mid
ventral sector of the insula evoked affiliative facial expressions. The present
study aimed to describe the cortical connections of this "affiliative field". To
this aim, we identified the region with electrical stimulation and injected
neural tracers to label incoming and outgoing projections. Our results show that
the insular field underlying emotional expression is part of a network involving
specific frontal, cingulate, temporal, and parietal areas, as well as the
amygdala, the basal ganglia, and thalamus, indicating that this sector of the
insula is a site of integration of motor, emotional, sensory and social
information. Together with our previous functional studies, this result
challenges the classic view of the insula as a multisensory area merely
reflecting bodily and internal visceral states. In contrast, it supports an
alternative perspective; that the emotional responses classically attributed to
the insular cortex are endowed with an enactive component intrinsic to each
social and emotional behavior.
PMID- 26441575
TI - Neurochemical measurements in the zebrafish brain.
AB - The zebrafish is an ideal model organism for behavioral genetics and
neuroscience. The high conservation of genes and neurotransmitter pathways
between zebrafish and other vertebrates permits the translation of research
between species. Zebrafish behavior can be studied at both larval and adult
stages and recent research has begun to establish zebrafish models for human
disease. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique that
permits the detection of neurotransmitter release and reuptake. In this study we
have used in vitro FSCV to measure the release of analytes in the adult zebrafish
telencephalon. We compare different stimulation methods and present a
characterization of neurochemical changes in the wild-type zebrafish brain. This
study represents the first FSCV recordings in zebrafish, thus paving the way for
neurochemical analysis of the fish brain.
PMID- 26441574
TI - Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin
Administration in Awake Rats.
AB - A growing body of literature has suggested that intranasal oxytocin (OT) or other
systemic routes of administration can alter prosocial behavior, presumably by
directly activating OT sensitive neural circuits in the brain. Yet there is no
clear evidence that OT given peripherally can cross the blood-brain barrier at
levels sufficient to engage the OT receptor. To address this issue we examined
changes in blood oxygen level-dependent (BOLD) signal intensity in response to
peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic
resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared
to OT (1 MUg/5 MUl) given directly to the brain via the lateral cerebroventricle.
Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas
and computational analysis, we reconstructed the distributed integrated neural
circuits identified with BOLD fMRI following central and peripheral OT. Both
routes of administration caused significant changes in BOLD signal within the
first 10 min of administration. As expected, central OT activated a majority of
brain areas known to express a high density of OT receptors, e.g., lateral
septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis.
This profile of activation was not matched by peripheral OT. The change in BOLD
signal to peripheral OT did not show any discernible dose-response.
Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in
addition to the cerebellum and several brainstem areas relevant to the autonomic
nervous system, including the solitary tract nucleus. The results from this
imaging study do not support a direct central action of peripheral OT on the
brain. Instead, the patterns of brain activity suggest that peripheral OT may
interact at the level of the olfactory bulb and through sensory afferents from
the autonomic nervous system to influence brain activity.
PMID- 26441576
TI - Effects of social sustainability signaling on neural valuation signals and taste
experience of food products.
AB - Value-based decision making occurs when individuals choose between different
alternatives and place a value on each alternative and its attributes. Marketing
actions frequently manipulate product attributes, by adding, e.g., health claims
on the packaging. A previous imaging study found that an emblem for organic
products increased willingness to pay (WTP) and activity in the ventral striatum
(VS). The current study investigated neural and behavioral processes underlying
the influence of Fair Trade (FT) labeling on food valuation and choice.
Sustainability is an important product attribute for many consumers, with FT
signals being one way to highlight ethically sustainable production. Forty
participants valuated products in combination with an FT emblem or no emblem and
stated their WTP in a bidding task while in an MRI scanner. After that,
participants tasted-objectively identical-chocolates, presented either as "FT" or
as "conventionally produced". In the fMRI task, WTP was significantly higher for
FT products. FT labeling increased activity in regions important for reward
processing and salience, that is, in the VS, anterior and posterior cingulate, as
well as superior frontal gyrus. Subjective value, that is, WTP was correlated
with activity in the ventromedial prefrontal cortex (vmPFC). We find that the
anterior cingulate, VS and superior frontal gyrus exhibit task-related increases
in functional connectivity to the vmPFC when an FT product was evaluated.
Effective connectivity analyses revealed a highly probable directed modulation of
the vmPFC by those three regions, suggesting a network which alters valuation
processes. We also found a significant taste-placebo effect, with higher
experienced taste pleasantness and intensity for FT labeled chocolates. Our
results reveal a possible neural mechanism underlying valuation processes of
certified food products. The results are important in light of understanding
current marketing trends as well as designing future interventions that aim at
positively influencing food choice.
PMID- 26441577
TI - The beneficial effect of testing: an event-related potential study.
AB - The enhanced memory performance for items that are tested as compared to being
restudied (the testing effect) is a frequently reported memory phenomenon.
According to the episodic context account of the testing effect, this beneficial
effect of testing is related to a process which reinstates the previously learnt
episodic information. Few studies have explored the neural correlates of this
effect at the time point when testing takes place, however. In this study, we
utilized the ERP correlates of successful memory encoding to address this issue,
hypothesizing that if the benefit of testing is due to retrieval-related
processes at test then subsequent memory effects (SMEs) should resemble the ERP
correlates of retrieval-based processing in their temporal and spatial
characteristics. Participants were asked to learn Swahili-German word pairs
before items were presented in either a testing or a restudy condition. Memory
performance was assessed immediately and 1-day later with a cued recall task.
Successfully recalling items at test increased the likelihood that items were
remembered over time compared to items which were only restudied. An ERP
subsequent memory contrast (later remembered vs. later forgotten tested items),
which reflects the engagement of processes that ensure items are recallable the
next day were topographically comparable with the ERP correlate of immediate
recollection (immediately remembered vs. immediately forgotten tested items).
This result shows that the processes which allow items to be more memorable over
time share qualitatively similar neural correlates with the processes that relate
to successful retrieval at test. This finding supports the notion that testing is
more beneficial than restudying on memory performance over time because of its
engagement of retrieval processes, such as the re-encoding of actively retrieved
memory representations.
PMID- 26441578
TI - Altered activity of the medial prefrontal cortex and amygdala during acquisition
and extinction of an active avoidance task.
AB - Altered medial prefrontal cortex (mPFC) and amygdala function is associated with
anxiety-related disorders. While the mPFC-amygdala pathway has a clear role in
fear conditioning, these structures are also involved in active avoidance. Given
that avoidance perseveration represents a core symptom of anxiety disorders, the
neural substrate of avoidance, especially its extinction, requires better
understanding. The present study was designed to investigate the activity,
particularly, inhibitory neuronal activity in mPFC and amygdala during
acquisition and extinction of lever-press avoidance in rats. Neural activity was
examined in the mPFC, intercalated cell clusters (ITCs) lateral (LA), basal (BA)
and central (CeA) amygdala, at various time points during acquisition and
extinction, using induction of the immediate early gene product, c-Fos. Neural
activity was greater in the mPFC, LA, BA, and ITC during the extinction phase as
compared to the acquisition phase. In contrast, the CeA was the only region that
was more activated during acquisition than during extinction. Our results
indicate inhibitory neurons are more activated during late phase of acquisition
and extinction in the mPFC and LA, suggesting the dynamic involvement of
inhibitory circuits in the development and extinction of avoidance response.
Together, these data start to identify the key brain regions important in active
avoidance behavior, areas that could be associated with avoidance perseveration
in anxiety disorders.
PMID- 26441579
TI - The longitudinal development of social and executive functions in late
adolescence and early adulthood.
AB - Our earlier work suggests that, executive functions and social cognition show
protracted development into late adolescence and early adulthood (Taylor et al.,
2013). However, it remains unknown whether these functions develop linearly or
non-linearly corresponding to dynamic changes to white matter density at these
age ranges. Executive functions are particularly in demand during the transition
to independence and autonomy associated with this age range (Ahmed and Miller,
2011). Previous research examining executive function (Romine and Reynolds, 2005)
and social cognition (Dumontheil et al., 2010a) in late adolescence has utilized
a cross sectional design. The current study employed a longitudinal design with
58 participants aged 17, 18, and 19 years completing social cognition and
executive function tasks, Wechsler Abbreviated Scale of Intelligence (Wechsler,
1999), Positive and Negative Affect Schedule (Watson et al., 1988), and Hospital
Anxiety and Depression Scale (Zigmond and Snaith, 1983) at Time 1 with follow up
testing 12-16 months later. Inhibition, rule detection, strategy generation and
planning executive functions and emotion recognition with dynamic stimuli showed
longitudinal development between time points. Self-report empathy and emotion
recognition functions using visual static and auditory stimuli were stable by age
17 whereas concept formation declined between time points. The protracted
development of some functions may reflect continued brain maturation into late
adolescence and early adulthood including synaptic pruning (Sowell et al., 2001)
and changes to functional connectivity (Stevens et al., 2007) and/or
environmental change. Clinical implications, such as assessing the effectiveness
of rehabilitation following Head Injury, are discussed.
PMID- 26441580
TI - Brain-derived neurotrophic factor serum levels correlate with cognitive
performance in Parkinson's disease patients with mild cognitive impairment.
AB - Brain-derived neurotrophic factor (BDNF) is a trophic factor regulating cell
survival and synaptic plasticity. Recent findings indicate that BDNF could be a
potential regulatory factor for cognitive functioning in normal and/or
neuropathological conditions. With regard to neurological disorders, recent data
suggest that individuals with Parkinson's disease (PD) may be affected by
cognitive deficits and that they have altered BDNF production. Therefore, the
hypothesis can be advanced that BDNF levels are associated with the cognitive
state of these patients. With this in mind, the present study was aimed at
exploring the relationship between BDNF serum levels and cognitive functioning in
PD patients with mild cognitive impairment (MCI). Thirteen PD patients with MCI
were included in the study. They were administered an extensive
neuropsychological test battery that investigated executive, episodic memory,
attention, visual-spatial and language domains. A single score was obtained for
each cognitive domain by averaging z-scores on tests belonging to that specific
domain. BDNF serum levels were measured by enzyme-linked immunoassay (ELISA).
Pearson's correlation analyses were performed between BDNF serum levels and
cognitive performance. Results showed a significant positive correlation between
BDNF serum levels and both attention (p < 0.05) and executive (p < 0.05) domains.
Moreover, in the executive domain we found a significant correlation between BDNF
levels and scores on tests assessing working memory and self
monitoring/inhibition. These preliminary data suggest that BDNF serum levels are
associated with cognitive state in PD patients with MCI. Given the role of BDNF
in regulating synaptic plasticity, the present findings give further support to
the hypothesis that this trophic factor may be a potential biomarker for
evaluating cognitive changes in PD and other neurological syndromes associated
with cognitive decline.
PMID- 26441581
TI - Gradual extinction reduces reinstatement.
AB - The current study investigated whether gradually reducing the frequency of
aversive stimuli during extinction can prevent the return of fear. Thirty-one
participants of a three-stage procedure (acquisition, extinction and a
reinstatement test on day 2) were randomly assigned to a standard extinction (SE)
and gradual extinction (GE) procedure. The two groups differed only in the
extinction procedure. While the SE group ran through a regular extinction process
without any negative events, the frequency of the aversive stimuli during the
extinction phase was gradually reduced for the GE group. The unconditioned
stimulus (US) was an air blast (5 bar, 10 ms). A spider and a scorpion were used
as conditioned stimuli (CS). The outcome variables were contingency ratings and
physiological measures (skin conductance response, SCR and startle response).
There were no differences found between the two groups for the acquisition and
extinction phases concerning contingency ratings, SCR, or startle response. GE
compared to SE significantly reduced the return of fear in the reinstatement test
for the startle response but not for SCR or contingency ratings. This study was
successful in translating the findings in rodent to humans. The results suggest
that the GE process is suitable for increasing the efficacy of fear extinction.
PMID- 26441582
TI - Cathodal HD-tDCS on the right V5 improves motion perception in humans.
AB - Brain lesions in the visual associative cortex are known to impair visual
perception, i.e., the capacity to correctly perceive different aspects of the
visual world, such as motion, color, or shapes. Visual perception can be
influenced by non-invasive brain stimulation such as transcranial direct current
stimulation (tDCS). In a recently developed technique called high definition (HD)
tDCS, small HD-electrodes are used instead of the sponge electrodes in the
conventional approach. This is believed to achieve high focality and precision
over the target area. In this paper we tested the effects of cathodal and anodal
HD-tDCS over the right V5 on motion and shape perception in a single blind,
within-subject, sham controlled, cross-over trial. The purpose of the study was
to prove the high focality of the stimulation only over the target area. Twenty
one healthy volunteers received 20 min of 2 mA cathodal, anodal and sham
stimulation over the right V5 and their performance on a visual test was
recorded. The results showed significant improvement in motion perception in the
left hemifield after cathodal HD-tDCS, but not in shape perception. Sham and
anodal HD-tDCS did not affect performance. The specific effect of influencing
performance of visual tasks by modulating the excitability of the neurons in the
visual cortex might be explained by the complexity of perceptual information
needed for the tasks. This provokes a "noisy" activation state of the encoding
neuronal patterns. We speculate that in this case cathodal HD-tDCS may focus the
correct perception by decreasing global excitation and thus diminishing the
"noise" below threshold.
PMID- 26441583
TI - Similarities and Differences in Decision-Making Impairments between Autism
Spectrum Disorder and Schizophrenia.
AB - Although individuals with autism spectrum disorders (ASD) and schizophrenia (SCH)
share overlapping characteristics and may perform similarly on many cognitive
tasks, cognitive dysfunctions common to both disorders do not necessarily share
the same underlying mechanisms. Decision-making is currently a major research
interest for both ASD and SCH. The aim of the present study was to make direct
comparisons of decision-making and disorder-specific underlying
neuropsychological mechanisms between the two disorders. Thirty-seven
participants with ASD, 46 patients with SCH, and 80 healthy controls (HC) were
assessed with the Iowa Gambling Task (IGT), which measures decision-making under
ambiguity, and the Game of Dice Task (GDT), which measures decision-making under
risk. The results revealed that both the ASD and SCH groups had deficits for both
the IGT and the GDT compared with the HC. More importantly, in the IGT,
participants with ASD displayed a preference for deck A, indicating that they had
more sensitivity to the magnitude of loss than to the frequency of loss, whereas
patients with SCH displayed a preference for deck B, indicating that they showed
more sensitivity to the frequency of loss than to the magnitude of loss. In the
GDT, the impaired performance might be due to the deficits in executive functions
in patients with SCH, whereas the impaired performance might be due to the
deficits in feedback processing in participants with ASD. These findings
demonstrate that there are similar impairments in decision-making tasks between
ASD and SCH; however, these two disorders may have different impairment
mechanisms.
PMID- 26441584
TI - Resting state functional connectivity differences between behavioral variant
frontotemporal dementia and Alzheimer's disease.
AB - INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal
dementia (bvFTD) are the most common types of early-onset dementia. Early
differentiation between both types of dementia may be challenging due to
heterogeneity and overlap of symptoms. Here, we apply resting state functional
magnetic resonance imaging (fMRI) to study functional brain connectivity
differences between AD and bvFTD. METHODS: We used resting state fMRI data of 31
AD patients, 25 bvFTD patients, and 29 controls from two centers specialized in
dementia. We studied functional connectivity throughout the entire brain,
applying two different analysis techniques, studying network-to-region and region
to-region connectivity. A general linear model approach was used to study group
differences, while controlling for physiological noise, age, gender, study
center, and regional gray matter volume. RESULTS: Given gray matter differences,
we observed decreased network-to-region connectivity in bvFTD between (a) lateral
visual cortical network and lateral occipital and cuneal cortex, and (b) auditory
system network and angular gyrus. In AD, we found decreased network-to-region
connectivity between the dorsal visual stream network and lateral occipital and
parietal opercular cortex. Region-to-region connectivity was decreased in bvFTD
between superior temporal gyrus and cuneal, supracalcarine, intracalcarine
cortex, and lingual gyrus. CONCLUSION: We showed that the pathophysiology of
functional brain connectivity is different between AD and bvFTD. Our findings
support the hypothesis that resting state fMRI shows disease-specific functional
connectivity differences and is useful to elucidate the pathophysiology of AD and
bvFTD. However, the group differences in functional connectivity are less
abundant than has been shown in previous studies.
PMID- 26441585
TI - Immunological findings in psychotic syndromes: a tertiary care hospital's CSF
sample of 180 patients.
AB - Immunological mechanisms and therapy approaches in psychotic syndromes were
recently supported by the discovery of autoantibody-associated limbic and non
limbic encephalitis. However, how clinical diagnostic procedures in psychiatry
should be adapted to these new insights is still unclear. In this study, we
analyzed the cerebrospinal fluid (CSF) and neuroimmunological alterations and
their association with cerebral MRI (cMRI) and electroencephalographic (EEG)
findings. From 2006 to 2013, we acquired 180 CSF samples from psychotic patients.
Between 2006 and 2009, CSF examinations were only performed in cases in which
organic brain disease was suspected. Since then, this procedure has been
integrated into our routine diagnostic workup. CSF basic diagnostics were
supplemented by measuring antineuronal antibodies against intracellular synaptic
antigens, antibodies against intracellular onconeural antigens, antibodies
against neuronal cell surface antigens and thyroid antibodies. In addition, cMRIs
and EEGs were conducted. We found white cell counts elevated in 3.4% of the
cases, albumin quotient elevated in 21.8%, and protein concentration elevated in
42.2%. Evidence of intrathecal immunoglobulin synthesis was found in 7.2% of the
cases. Antibodies measured against neuronal cell surface antigens were positive
in 3.2%. Reactivity on antibodies against intracellular onconeural antigens were
detected in 3.5%. Serum thyroid antibodies were elevated in 24.7%. Abnormalities
were found in 39.5% of cMRIs and in 34.3% of EEGs. The main finding of our study
was the high prevalence of CSF and autoantibody abnormalities in 54.4% of
psychotic patients. In combination with cMRIs and EEGs, 75.6% showed abnormal
findings. Our results are discussed with regard to the concept of immunological
encephalopathy. Future studies should analyze the efficacy of immunomodulatory
therapies.
PMID- 26441587
TI - Thinking in three dimensions: a different point of view for understanding autism.
PMID- 26441586
TI - Home-based neurologic music therapy for upper limb rehabilitation with stroke
patients at community rehabilitation stage-a feasibility study protocol.
AB - BACKGROUND: Impairment of upper limb function following stroke is more common
than lower limb impairment and is also more resistant to treatment. Several lab
based studies with stroke patients have produced statistically significant gains
in upper limb function when using musical instrument playing and techniques where
rhythm acts as an external time-keeper for the priming and timing of upper limb
movements. METHODS: For this feasibility study a small sample size of 14
participants (3-60 months post stroke) has been determined through clinical
discussion between the researcher and study host in order to test for management,
feasibility and effects, before planning a larger trial determined through power
analysis. A cross-over design with five repeated measures will be used, whereby
participants will be randomized into either a treatment (n = 7) or wait list
control (n = 7) group. Intervention will take place twice weekly over 6 weeks.
The ARAT and 9HPT will be used to measure for quantitative gains in arm function
and finger dexterity, pre/post treatment interviews will serve to investigate
treatment compliance and tolerance. A lab based EEG case comparison study will be
undertaken to explore audio-motor coupling, brain connectivity and neural
reorganization with this intervention, as evidenced in similar studies.
DISCUSSION: Before evaluating the effectiveness of a home-based intervention in a
larger scale study, it is important to assess whether implementation of the trial
methodology is feasible. This study investigates the feasibility, efficacy and
patient experience of a music therapy treatment protocol comprising a chart of 12
different instrumental exercises and variations, which aims at promoting
measurable changes in upper limb function in hemiparetic stroke patients. The
study proposes to examine several new aspects including home-based treatment and
dosage, and will provide data on recruitment, adherence and variability of
outcomes.
PMID- 26441588
TI - Multi-modal representation of effector modality in frontal cortex during rule
switching.
AB - We report a functional magnetic resonance imaging (fMRI) study which investigated
whether brain areas involved in updating task rules within the frontal lobe of
the cerebral cortex show activity related to the modality of motor response used
in the task. Participants performed a rule switching task using different
effector modalities. In some blocks participants responded with left/right button
presses, whilst in other blocks left/right saccades were required. The color of a
Cue event instructed a left or right response based upon a rule, followed by a
Feedback which indicated whether the rule was to stay the same or "Flip" on the
next trial. The findings revealed variation in the locus of activity within the
ventrolateral frontal cortex dependent upon effector modality. Other frontal
areas showed no significant difference in activity between response epochs but
changed their pattern of connectivity with posterior cortical areas dependent
upon response. Multivariate analysis revealed that the pattern of activity evoked
by Flip rule Feedbacks within an apparently supra modal frontal region
(dorsolateral frontal cortex) discriminated between response epochs. The results
are consistent with the existence of multi-modal representations of stimulus
response (SR) rules within the frontal cerebral cortex.
PMID- 26441589
TI - Research domain criteria: a final paradigm for psychiatry?
PMID- 26441590
TI - Social anxiety disorder and the psychobiology of self-consciousness.
AB - Individuals with social anxiety disorder (SAD) are characterized by fear or
anxiety about social situations, but also by important alterations in self
referential processing. Given advances in our understanding of the neurocircuitry
and neurochemistry of SAD, the question arises of the relationship between this
research and an emergent literature on the psychobiology of self and self
consciousness. A number of investigations of SAD have highlighted altered
activity in the medial prefrontal cortex (mPFC; involved in self-representation),
insula (involved in interoceptive processing), and other structures that play a
role in bodily self-consciousness, as well as the potential value of
interventions such as selective serotonin reuptake inhibitors (SSRI) and self
focused reappraisal in normalizing such changes. Future studies to more closely
investigate associations between psychobiological alterations and changes in self
related processing in SAD, may be useful in shedding additional light on both SAD
and self-consciousness.
PMID- 26441591
TI - Response: A commentary on: "Neural overlap in processing music and speech".
PMID- 26441592
TI - Neural regions discriminating contextual information as conveyed through the
learned preferences of others.
AB - The human brain consists of a network of regions that are engaged when one
observes the movements of others. Observing unexpected movements, as defined by
the context, often elicits greater activity, particularly in the right posterior
superior temporal sulcus (pSTS). This implies that observers use contextual
information to form expectations about an agent's goal and subsequent movements.
The current study sought to identify regions that support the formation of these
context-dependent expectations, with the pSTS being one candidate, given the
consistent contextual modulation of its activity. We presented participants with
fictitious individuals who had emotion-dependent food preferences, and instructed
participants to indicate which food they expected each individual to choose based
on the individual's current emotional state. Each individual's preference and
emotional state therefore created a context that informed the observer's
expectation of the individual's choice. Multi-voxel pattern analysis (MVPA) was
used to assess if these different contexts could be discriminated in the pSTS and
elsewhere in the brain. No evidence for context discrimination was found in the
pSTS. Context discrimination was found instead a network of other brain regions
including the anterior medial prefrontal cortex (amPFC), bilateral parietal
cortex, left middle temporal gyrus (L MTG) and left anterior temporal lobe (L
ATL), which have been previously associated with context processing, and semantic
and memory retrieval. All together, these regions possibly support the formation
of context-dependent expectations of an agent's goal.
PMID- 26441593
TI - The dissociation between command following and communication in disorders of
consciousness: an fMRI study in healthy subjects.
AB - Neuroimaging studies have identified a subgroup of patients with a Disorder of
Consciousness (DOC) who, while being behaviorally non-responsive, are
nevertheless able to follow commands by modulating their brain activity in motor
imagery (MI) tasks. These techniques have even allowed for binary communication
in a small number of DOC patients. However, the majority of patients who can
follow commands are unable to use their responses to communicate. A similar
dissociation between present command following (CF) and absent communication
abilities has been reported in overt behavioral assessments. However, the neural
correlates of this dissociation in both overt and covert modalities are unknown.
Here, we used functional magnetic resonance imaging (fMRI) to explore the neural
mechanisms underlying CF and selection of responses for binary communication
using either executed or imagined movements. Fifteen healthy participants
executed or imagined two different types of arm movements that were either pre
determined by the experimenters (CF) or decided by them (action selection, AS).
Action selection involved greater activity in high-level associative areas in
frontal and parietal regions than CF. Additionally, motor execution (ME), as
compared to MI, activated contralateral motor cortex, while the opposite contrast
revealed activation in the ipsilateral sensorimotor cortex and the left inferior
frontal gyrus. Importantly, there was no interaction between the task (CF/AS) and
modality (MI/ME). Our results suggest that the neural processes involved in
following a motor command or selecting between two motor actions are not
dependent on how the response is expressed (via ME/MI). They also suggest a
potential neural basis for the distinction in cognitive abilities seen in DOC
patients.
PMID- 26441594
TI - A closer look at cognitive control: differences in resource allocation during
updating, inhibition and switching as revealed by pupillometry.
AB - The present study investigated resource allocation, as measured by pupil
dilation, in tasks measuring updating (2-Back task), inhibition (Stroop task) and
switching (Number Switch task). Because each cognitive control component has
unique characteristics, differences in patterns of resource allocation were
expected. Pupil and behavioral data from 35 participants were analyzed. In the 2
Back task (requiring correct matching of current stimulus identity at trial p
with the stimulus two trials back, p -2) we found that better performance (low
total of errors made in the task) was positively correlated to the mean pupil
dilation during correctly responding to targets. In the Stroop task, pupil
dilation on incongruent trials was higher than those on congruent trials.
Incongruent vs. congruent trial pupil dilation differences were positively
related to reaction time differences between incongruent and congruent trials.
Furthermore, on congruent Stroop trials, pupil dilation was negatively related to
reaction times, presumably because more effort allocation paid off in terms of
faster responses. In addition, pupil dilation on correctly-responded-to congruent
trials predicted a weaker Stroop interference effect in terms of errors, probably
because pupil dilation on congruent trials were diagnostic of task motivation,
resulting in better performance. In the Number Switch task we found higher pupil
dilation in switch as compared to non-switch trials. On the Number Switch task,
pupil dilation was not related to performance. We also explored error-related
pupil dilation in all tasks. The results provide new insights in the diversity of
the cognitive control components in terms of resource allocation as a function of
individual differences, task difficulty and error processing.
PMID- 26441595
TI - Altered connectivity of the dorsal and ventral visual regions in dyslexic
children: a resting-state fMRI study.
AB - While there is emerging evidence from behavioral studies that visual attention
skills are impaired in dyslexia, the corresponding neural mechanism (i.e.,
deficits in the dorsal visual region) needs further investigation. We used
resting-state fMRI to explore the functional connectivity (FC) patterns of the
left intraparietal sulcus (IPS) and the visual word form area (VWFA) in dyslexic
children (N = 21, age mean = 12) and age-matched controls (N = 26, age mean =
12). The results showed that the left IPS and the VWFA were functionally
connected to each other in both groups and that both were functionally connected
to left middle frontal gyrus (MFG). Importantly, we observed significant group
differences in FC between the left IPS and the left MFG and between the VWFA and
the left MFG. In addition, the strengths of the identified FCs were significantly
correlated with the score of fluent reading, which required obvious eye movement
and visual attention processing, but not with the lexical decision score. We
conclude that dyslexics have deficits in the network composed of the prefrontal,
dorsal visual and ventral visual regions and may have a lack of modulation from
the left MFG to the dorsal and ventral visual regions.
PMID- 26441596
TI - Perceptual decision-making difficulty modulates feedforward effective
connectivity to the dorsolateral prefrontal cortex.
AB - Diverse cortical structures are known to coordinate activity as a network in
relaying and processing of visual information to discriminate visual objects.
However, how this discrimination is achieved is still largely unknown. To
contribute to answering this question, we used face-house categorization tasks
with three levels of noise in face and house images in functional magnetic
resonance imaging (fMRI) experiments involving thirty-three participants. The
behavioral performance error and response time (RT) were correlated with noise in
face-house images. We then built dynamical causal models (DCM) of fMRI blood
oxygenation level dependent (BOLD) signals from the face and house category
specific regions in ventral temporal (VT) cortex, the fusiform face area (FFA)
and parahippocampal place area (PPA), and the dorsolateral prefrontal cortex
(dlPFC). We found a strong feed-forward intrinsic connectivity pattern from FFA
and PPA to dlPFC. Importantly, the feed-forward connectivity to dlPFC was
significantly modulated by the perception of both faces and houses. The dlPFC
BOLD activity, the connectivity from FFA and PPA to the dlPFC all increased with
noise level. These results suggest that the FFA-PPA-dlPFC network plays an
important role for relaying and integrating competing sensory information to
arrive at perceptual decisions.
PMID- 26441597
TI - Gender differences in human single neuron responses to male emotional faces.
AB - Well-documented differences in the psychology and behavior of men and women have
spurred extensive exploration of gender's role within the brain, particularly
regarding emotional processing. While neuroanatomical studies clearly show
differences between the sexes, the functional effects of these differences are
less understood. Neuroimaging studies have shown inconsistent locations and
magnitudes of gender differences in brain hemodynamic responses to emotion. To
better understand the neurophysiology of these gender differences, we analyzed
recordings of single neuron activity in the human brain as subjects of both
genders viewed emotional expressions. This study included recordings of single
neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala
(236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and
ventromedial prefrontal cortex (n = 174). Neural activity was recorded while
participants viewed a series of avatar male faces portraying positive, negative
or neutral expressions. Significant gender differences were found in the left
amygdala, where 23% (n = 15/66) of neurons in men were significantly affected by
facial emotion, vs. 8% (n = 6/76) of neurons in women. A Fisher's exact test
comparing the two ratios found a highly significant difference between the two (p
< 0.01). These results show specific differences between genders at the single
neuron level in the human amygdala. These differences may reflect gender-based
distinctions in evolved capacities for emotional processing and also demonstrate
the importance of including subject gender as an independent factor in future
studies of emotional processing by single neurons in the human amygdala.
PMID- 26441598
TI - Editorial: What can we make of theories of embodiment and the role of the human
mirror neuron system?
PMID- 26441599
TI - Mu rhythm desynchronization by tongue thrust observation.
AB - We aimed to investigate the mu rhythm in the sensorimotor area during tongue
thrust observation and to obtain an answer to the question as to how subtle non
verbal orofacial movement observation activates the sensorimotor area. Ten
healthy volunteers performed finger tap execution, tongue thrust execution, and
tongue thrust observation. The electroencephalogram (EEG) was recorded from 128
electrodes placed on the scalp, and regions of interest were set at sensorimotor
areas. The event-related desynchronization (ERD) and event-related
synchronization (ERS) for the mu rhythm (8-13 Hz) and beta (13-25 Hz) bands were
measured. Tongue thrust observation induced mu rhythm ERD, and the ERD was
detected at the left hemisphere regardless whether the observed tongue thrust was
toward the left or right. Mu rhythm ERD was also recorded during tongue thrust
execution. However, temporal analysis revealed that the ERD associated with
tongue thrust observation preceded that associated with execution by
approximately 2 s. Tongue thrust observation induces mu rhythm ERD in
sensorimotor cortex with left hemispheric dominance.
PMID- 26441600
TI - An engineered glove for investigating the neural correlates of finger movements
using functional magnetic resonance imaging.
AB - Objective measurement of concomitant finger motor performance is recommended for
functional magnetic resonance imaging (fMRI) studies investigating brain activity
during finger tapping tasks, because performance modality and ability can
influence the selection of different neural networks. In this study, we present a
novel glove system for quantitative evaluation of finger opposition movements
during fMRI (called Glove Analyzer for fMRI, GAF). Several tests for magnetic
resonance (MR) compatibility were performed concerning magnet forces, image
artifacts and right functioning of the system. Then, pilot fMRI of finger
opposition tasks were conducted at 1.5T and 3T to investigate the neural
correlates of sequences of finger opposition movements with the right hand, with
simultaneous behavioral recording by means of GAF. All the MR compatibility tests
succeeded, and the fMRI analysis revealed mainly the activation of the left
sensorimotor areas and right cerebellum, regions that are known to be involved in
finger movements. No artifactual clusters were detected in the activation maps.
At the same time, through the parameters calculated by GAF it was possible to
describe the sensorimotor strategy adopted by the subjects during the required
task. Thus, the proposed device resulted to be MR compatible and can be useful
for future fMRI studies investigating the neural correlates of finger opposition
movements, allowing follow-up studies and comparisons among different groups of
patients.
PMID- 26441601
TI - Neural correlates of reward processing in healthy siblings of patients with
schizophrenia.
AB - Deficits in motivational behavior and psychotic symptoms often observed in
schizophrenia (SZ) may be driven by dysfunctional reward processing (RP). RP can
be divided in two different stages; reward anticipation and reward consumption.
Aberrant processing during reward anticipation seems to be related to SZ. Studies
in patients with SZ have found less activation in the ventral striatum (VS)
during anticipation of reward, but these findings do not provide information on
effect of the genetic load on reward processing. Therefore, this study
investigated RP in healthy first-degree relatives of SZ patients. The sample
consisted of 94 healthy siblings of SZ patients and 57 healthy controls.
Participants completed a classic RP task, the Monetary Incentive Delay task,
during functional magnetic resonance imaging (fMRI). As expected, there were no
behavioral differences between groups. In contrast to our expectations, we found
no differences in any of the anticipatory reward related brain areas (region of
interest analyses). Whole-brain analyses did reveal group differences during both
reward anticipation and reward consumption; during reward anticipation siblings
showed less deactivation in the insula, posterior cingulate cortex (PCC) and
medial frontal gyrus (MFG) than controls. During reward consumption siblings
showed less deactivation in the PCC and the right MFG compared to controls and
activation in contrast to deactivation in controls in the precuneus and the left
MFG. Exclusively in siblings, MFG activity correlated positively with subclinical
negative symptoms. These regions are typically associated with the default mode
network (DMN), which normally shows decreases in activation during task-related
cognitive processes. Thus, in contrast to prior literature in patients with SZ,
the results do not point to altered brain activity in classical RP brain areas,
such as the VS. However, the weaker deactivation found outside the reward-related
network in siblings could indicate reduced task-related suppression (i.e.,
hyperactivation) of the DMN. The presence of DMN hyperactivation during reward
anticipation and reward consumption might indicate that siblings of patients with
SZ have a higher baseline level of DMN activation and possible abnormal network
functioning.
PMID- 26441602
TI - Implicit learning of predictable sound sequences modulates human brain responses
at different levels of the auditory hierarchy.
AB - Deviant stimuli, violating regularities in a sensory environment, elicit the
mismatch negativity (MMN), largely described in the Event-Related Potential
literature. While it is widely accepted that the MMN reflects more than basic
change detection, a comprehensive description of mental processes modulating this
response is still lacking. Within the framework of predictive coding, deviance
processing is part of an inference process where prediction errors (the mismatch
between incoming sensations and predictions established through experience) are
minimized. In this view, the MMN is a measure of prediction error, which yields
specific expectations regarding its modulations by various experimental factors.
In particular, it predicts that the MMN should decrease as the occurrence of a
deviance becomes more predictable. We conducted a passive oddball EEG study and
manipulated the predictability of sound sequences by means of different temporal
structures. Importantly, our design allows comparing mismatch responses elicited
by predictable and unpredictable violations of a simple repetition rule and
therefore departs from previous studies that investigate violations of different
time-scale regularities. We observed a decrease of the MMN with predictability
and interestingly, a similar effect at earlier latencies, within 70 ms after
deviance onset. Following these pre-attentive responses, a reduced P3a was
measured in the case of predictable deviants. We conclude that early and late
deviance responses reflect prediction errors, triggering belief updating within
the auditory hierarchy. Beside, in this passive study, such perceptual inference
appears to be modulated by higher-level implicit learning of sequence statistical
structures. Our findings argue for a hierarchical model of auditory processing
where predictive coding enables implicit extraction of environmental
regularities.
PMID- 26441603
TI - LTP-like plasticity in the visual system and in the motor system appear related
in young and healthy subjects.
AB - LTP-like plasticity measured by visual evoked potentials (VEP) can be induced in
the intact human brain by presenting checkerboard reversals. Also associated with
LTP-like plasticity, around two third of participants respond to transcranial
magnetic stimulation (TMS) with a paired-associate stimulation (PAS) protocol
with a potentiation of their motor evoked potentials. LTP-like processes are also
required for verbal and motor learning tasks. We compared effect sizes, responder
rates and intercorrelations as well as the potential influence of attention
between these four assessments in a group of 37 young and healthy volunteers. We
observed a potentiation effect of the N75 and P100 VEP component which positively
correlated with plasticity induced by PAS. Subjects with a better subjective
alertness were more likely to show PAS and VEP potentiation. No correlation was
found between the other assessments. Effect sizes and responder rates of VEP
potentiation were higher compared to PAS. Our results indicate a high variability
of LTP-like effects and no evidence for a system-specific nature. As a
consequence, studies wishing to assess individual levels of LTP-like plasticity
should employ a combination of multiple assessments.
PMID- 26441605
TI - Use the brain: complementary methods to analyse the effects of motivational
music.
PMID- 26441604
TI - Expert and crowd-sourced validation of an individualized sleep spindle detection
method employing complex demodulation and individualized normalization.
AB - A spindle detection method was developed that: (1) extracts the signal of
interest (i.e., spindle-related phasic changes in sigma) relative to ongoing
"background" sigma activity using complex demodulation, (2) accounts for
variations of spindle characteristics across the night, scalp derivations and
between individuals, and (3) employs a minimum number of sometimes arbitrary,
user-defined parameters. Complex demodulation was used to extract instantaneous
power in the spindle band. To account for intra- and inter-individual
differences, the signal was z-score transformed using a 60 s sliding window, per
channel, over the course of the recording. Spindle events were detected with a z
score threshold corresponding to a low probability (e.g., 99th percentile).
Spindle characteristics, such as amplitude, duration and oscillatory frequency,
were derived for each individual spindle following detection, which permits
spindles to be subsequently and flexibly categorized as slow or fast spindles
from a single detection pass. Spindles were automatically detected in 15 young
healthy subjects. Two experts manually identified spindles from C3 during Stage 2
sleep, from each recording; one employing conventional guidelines, and the other,
identifying spindles with the aid of a sigma (11-16 Hz) filtered channel. These
spindles were then compared between raters and to the automated detection to
identify the presence of true positives, true negatives, false positives and
false negatives. This method of automated spindle detection resolves or avoids
many of the limitations that complicate automated spindle detection, and performs
well compared to a group of non-experts, and importantly, has good external
validity with respect to the extant literature in terms of the characteristics of
automatically detected spindles.
PMID- 26441606
TI - Commentary: "Neural signatures of intransitive preferences".
PMID- 26441607
TI - Atypical delayed auditory feedback effect and Lombard effect on speech production
in high-functioning adults with autism spectrum disorder.
AB - Individuals with autism spectrum disorder (ASD) show impaired social interaction
and communication, which may be related to their difficulties in speech
production. To investigate the mechanisms of atypical speech production in this
population, we examined feedback control by delaying the auditory feedback of
their own speech, which degraded speech fluency. We also examined feedforward
control by adding loud pink noise to the auditory feedback, which led to
increased vocal effort in producing speech. The results of Japanese speakers show
that, compared with neurotypical (NT) individuals, high-functioning adults with
ASD (including Asperger's disorder, autistic disorder, and pervasive
developmental disorder not otherwise specified) were more affected by delayed
auditory feedback but less affected by external noise. These findings indicate
that, in contrast to NT individuals, those with ASD relied more on feedback
control than on feedforward control in speech production, which is consistent
with the hypothesis that this population exhibits attenuated Bayesian priors.
PMID- 26441608
TI - Depth discrimination of constant angular size stimuli in action space: role of
accommodation and convergence cues.
AB - In our daily life experience, the angular size of an object correlates with its
distance from the observer, provided that the physical size of the object remains
constant. In this work, we investigated depth perception in action space (i.e.,
beyond the arm reach), while keeping the angular size of the target object
constant. This was achieved by increasing the physical size of the target object
as its distance to the observer increased. To the best of our knowledge, this is
the first time that a similar protocol has been tested in action space, for
distances to the observer ranging from 1.4-2.4 m. We replicated the task in
virtual and real environments and we found that the performance was significantly
different between the two environments. In the real environment, all participants
perceived the depth of the target object precisely. Whereas, in virtual reality
(VR) the responses were significantly less precise, although, still above chance
level in 16 of the 20 observers. The difference in the discriminability of the
stimuli was likely due to different contributions of the convergence and the
accommodation cues in the two environments. The values of Weber fractions
estimated in our study were compared to those reported in previous studies in
peripersonal and action space.
PMID- 26441609
TI - Task-related activity in sensorimotor cortex in Parkinson's disease and essential
tremor: changes in beta and gamma bands.
AB - In Parkinson's disease patients in the OFF medication state, basal ganglia local
field potentials exhibit changes in beta and gamma oscillations that correlate
with reduced voluntary movement, manifested as rigidity and akinesia. However,
magnetoencephalography and low-resolution electrocorticography (ECoG) studies in
Parkinson's patients suggest that changes in sensorimotor cortical oscillations
differ from those of the basal ganglia. To more clearly define the role of
sensorimotor cortex oscillatory activity in Parkinson's, we performed
intraoperative, high-resolution (4 mm spacing) ECoG recordings in 10 Parkinson's
patients (2 females, ages 47-72) undergoing deep brain stimulation (DBS) lead
placement in the awake, OFF medication state. We analyzed ECoG potentials during
a computer-controlled reaching task designed to separate movement preparation
from movement execution and compared findings to similar invasive recordings in
eight patients with essential tremor (3 females, ages 59-78), a condition not
associated with rigidity or akinesia. We show that (1) cortical beta spectral
power at rest does not differ between Parkinson's and essential tremor patients
(p = 0.85), (2) early motor preparation in Parkinson's patients in the OFF
medication state is associated with a larger beta desynchronization compared to
patients with essential tremor (p = 0.0061), and (3) cortical broadband gamma
power is elevated in Parkinson's patients compared to essential tremor patients
during both rest and task recordings (p = 0.004). Our findings suggest an
oscillatory profile in sensorimotor cortex of Parkinson's patients that, in
contrast to the basal ganglia, may act to promote movement to oppose the anti
kinetic bias of the dopamine-depleted state.
PMID- 26441611
TI - Beauty and the beholder: the role of visual sensitivity in visual preference.
AB - For centuries, the essence of aesthetic experience has remained one of the most
intriguing mysteries for philosophers, artists, art historians and scientists
alike. Recently, views emphasizing the link between aesthetics, perception and
brain function have become increasingly prevalent (Ramachandran and Hirstein,
1999; Zeki, 1999; Livingstone, 2002; Ishizu and Zeki, 2013). The link between art
and the fractal-like structure of natural images has also been highlighted
(Spehar et al., 2003; Graham and Field, 2007; Graham and Redies, 2010). Motivated
by these claims and our previous findings that humans display a consistent
preference across various images with fractal-like statistics, here we explore
the possibility that observers' preference for visual patterns might be related
to their sensitivity for such patterns. We measure sensitivity to simple visual
patterns (sine-wave gratings varying in spatial frequency and random textures
with varying scaling exponent) and find that they are highly correlated with
visual preferences exhibited by the same observers. Although we do not attempt to
offer a comprehensive neural model of aesthetic experience, we demonstrate a
strong relationship between visual sensitivity and preference for simple visual
patterns. Broadly speaking, our results support assertions that there is a close
relationship between aesthetic experience and the sensory coding of natural
stimuli.
PMID- 26441610
TI - Recovery of resting brain connectivity ensuing mild traumatic brain injury.
AB - Brains reveal amplified plasticity as they recover from an injury. We aimed to
define time dependent plasticity changes in patients recovering from mild
traumatic brain injury (mTBI). Twenty-five subjects with mild head injury were
longitudinally evaluated within 36 h, 3 and 6 months using resting state
functional connectivity (RSFC). Region of interest (ROI) based connectivity
differences over time within the patient group and in comparison with a healthy
control group were analyzed at p < 0.005. We found 33 distinct ROI pairs that
revealed significant changes in their connectivity strength with time. Within 3
months, the majority of the ROI pairs had decreased connectivity in mTBI
population, which increased and became comparable to healthy controls at 6
months. Within this diffuse decreased connectivity in the first 3 months, there
were also few regions with increased connections. This hyper connectivity
involved the salience network and default mode network within 36 h, and lingual,
inferior frontal and fronto-parietal networks at 3 months. Our findings in a
fairly homogenous group of patients with mTBI evaluated during the 6 month window
of recovery defines time varying brain connectivity changes as the brain recovers
from an injury. A majority of these changes were seen in the frontal and parietal
lobes between 3 and 6 months after injury. Hyper connectivity of several networks
supported normal recovery in the first 6 months and it remains to be seen in
future studies whether this can predict an early and efficient recovery of brain
function.
PMID- 26441612
TI - Effects of broken affordance on visual extinction.
AB - Previous studies have shown that visual extinction can be reduced if two objects
are positioned to "afford" an action. Here we tested if this affordance effect
was disrupted by "breaking" the affordance, i.e., if one of the objects actively
used in the action had a broken handle. We assessed the effects of broken
affordance on recovery from extinction in eight patients with right hemisphere
lesions and left-sided extinction. Patients viewed object pairs that were or were
not commonly used together and that were positioned for left- or right-hand
actions. In the unrelated pair conditions, either two tools or two objects were
presented. In line with previous research (e.g., Riddoch et al., 2006),
extinction was reduced when action-related object pairs and when unrelated tool
pairs were presented compared to unrelated object pairs. There was no significant
difference in recovery rate between action-related (object-tool) and unrelated
tool pairs. In addition, performance with action-related objects decreased when
the tool appeared on the ipsilesional side compared to when it was on the
contralesional side, but only when the tool handle was intact. There were minimal
effects of breaking the handle of an object rather than a tool, and there was no
effect of breaking the handle on either tools or objects on single item trials.
The data suggest that breaking the handle of a tool lessens the degree to which
it captures attention, with this attentional capture being strongest when the
tool appears on the ipsilesional side. The capture of attention by the
ipsilesional item then reduces the chance of detecting the contralesional
stimulus. This attentional capture effect is mediated by the affordance to the
intact tool.
PMID- 26441613
TI - The neural representation of Arabic digits in visual cortex.
AB - In this study, we investigated how Arabic digits are represented in the visual
cortex, and how their representation changes throughout the ventral visual
processing stream, compared to the representation of letters. We probed these
questions with two functional magnetic resonance imaging (fMRI) experiments. In
Experiment 1, we explored whether we could find brain regions that were more
activated for digits than for number words in a subtraction task. One such region
was detected in lateral occipital cortex. However, the activity in this region
might have been confounded by string length-number words contain more characters
than digits. We therefore conducted a second experiment in which string length
was systematically controlled. Experiment 2 revealed that the findings of the
first experiment were task dependent (as it was only observed in a task in which
numerosity was relevant) or stimulus dependent (as it was only observed when the
number of characters of a stimulus was not controlled). We further explored the
characteristics of the activation patterns for digit and letter strings across
the ventral visual processing stream through multi-voxel pattern analyses. We
found an alteration in representations throughout the ventral processing stream
from clustering based on amount of visual information in primary visual cortex
(V1) towards clustering based on symbolic stimulus category higher in the visual
hierarchy. The present findings converge to the conclusion that in the ventral
visual system, as far as can be detected with fMRI, the distinction between
Arabic digits and letter strings is represented in terms of distributed patterns
rather than separate regions.
PMID- 26441614
TI - The neurochemistry and social flow of singing: bonding and oxytocin.
AB - Music is used in healthcare to promote physical and psychological well-being. As
clinical applications of music continue to expand, there is a growing need to
understand the biological mechanisms by which music influences health. Here we
explore the neurochemistry and social flow of group singing. Four participants
from a vocal jazz ensemble were conveniently sampled to sing together in two
separate performances: pre-composed and improvised. Concentrations of plasma
oxytocin and adrenocorticotropic hormone (ACTH) were measured before and after
each singing condition to assess levels of social affiliation, engagement and
arousal. A validated assessment of flow state was administered after each singing
condition to assess participants' absorption in the task. The feasibility of the
research methods were assessed and initial neurochemical data was generated on
group singing. Mean scores of the flow state scale indicated that participants
experienced flow in both the pre-composed (M = 37.06) and improvised singing
conditions (M = 34.25), with no significant difference between conditions. ACTH
concentrations decreased in both conditions, significantly so in the pre-composed
singing condition, which may have contributed to the social flow experience. Mean
plasma oxytocin levels increased only in response to improvised singing, with no
significant difference between improvised and pre-composed singing conditions
observed. The results indicate that group singing reduces stress and arousal, as
measured by ACTH, and induces social flow in participants. The effects of pre
composed and improvised group singing on oxytocin are less clear. Higher levels
of plasma oxytocin in the improvised condition may perhaps be attributed to the
social effects of improvising musically with others. Further research with a
larger sample size is warranted.
PMID- 26441616
TI - Corrigendum: Exploring associations between gaze patterns and putative human
mirror neuron system activity.
AB - [This corrects the article on p. 396 in vol. 9, PMID: 26236215.].
PMID- 26441615
TI - Rehabilitation of aphasia: application of melodic-rhythmic therapy to Italian
language.
AB - Aphasia is a complex disorder, frequent after stroke (with an incidence of 38%),
with a detailed pathophysiological characterization. Effective approaches are
crucial for devising an efficient rehabilitative strategy, in order to address
the everyday life and professional disability. Several rehabilitative procedures
are based on psycholinguistic, cognitive, psychosocial or pragmatic approaches,
including amongst those with a neurobehavioral approach the Melodic Intonation
Therapy (MIT). Van Eeckhout's adaptation of MIT to French language (Melodic
Rhythmic Therapy: MRT) has implemented the training strategy by adding a rhythmic
structure reproducing French prosody. The purpose of this study was to adapt MRT
rehabilitation procedures to Italian language and to verify its efficacy in a
group of six chronic patients (five males) with severe non-fluent aphasia and
without specific aphasic treatments during the previous 9 months. The patients
were treated 4 days a week for 16 weeks, with sessions of 30-40 min. They were
assessed 6 months after the end of the treatment (follow-up). The patients showed
a significant improvement at the Aachener Aphasie Test (AAT) in different fields
of spontaneous speech, with superimposable results at the follow-up. Albeit
preliminary, these findings support the use of MRT in the rehabilitation after
stroke. Specifically, MRT seems to benefit from its stronger structure than the
available stimulation-facilitation procedures and allows a better quantification
of the rehabilitation efficacy.
PMID- 26441617
TI - Response: Commentary: Viewing photos and reading nouns of natural graspable
objects similarly modulate motor responses.
PMID- 26441618
TI - Synchronization by the hand: the sight of gestures modulates low-frequency
activity in brain responses to continuous speech.
AB - During social interactions, speakers often produce spontaneous gestures to
accompany their speech. These coordinated body movements convey communicative
intentions, and modulate how listeners perceive the message in a subtle, but
important way. In the present perspective, we put the focus on the role that
congruent non-verbal information from beat gestures may play in the neural
responses to speech. Whilst delta-theta oscillatory brain responses reflect the
time-frequency structure of the speech signal, we argue that beat gestures
promote phase resetting at relevant word onsets. This mechanism may facilitate
the anticipation of associated acoustic cues relevant for prosodic/syllabic-based
segmentation in speech perception. We report recently published data supporting
this hypothesis, and discuss the potential of beats (and gestures in general) for
further studies investigating continuous AV speech processing through low
frequency oscillations.
PMID- 26441619
TI - Neurovascular coupling: a parallel implementation.
AB - A numerical model of neurovascular coupling (NVC) is presented based on neuronal
activity coupled to vasodilation/contraction models via the astrocytic mediated
perivascular K(+) and the smooth muscle cell (SMC) Ca(2+) pathway termed a
neurovascular unit (NVU). Luminal agonists acting on P2Y receptors on the
endothelial cell (EC) surface provide a flux of inositol trisphosphate (IP3) into
the endothelial cytosol. This concentration of IP3 is transported via gap
junctions between EC and SMC providing a source of sarcoplasmic derived Ca(2+) in
the SMC. The model is able to relate a neuronal input signal to the corresponding
vessel reaction (contraction or dilation). A tissue slice consisting of blocks,
each of which contain an NVU is connected to a space filling H-tree, simulating a
perfusing arterial tree (vasculature) The model couples the NVUs to the vascular
tree via a stretch mediated Ca(2+) channel on both the EC and SMC. The SMC is
induced to oscillate by increasing an agonist flux in the EC and hence increased
IP3 induced Ca(2+) from the SMC stores with the resulting calcium-induced calcium
release (CICR) oscillation inhibiting NVC thereby relating blood flow to vessel
contraction and dilation following neuronal activation. The coupling between the
vasculature and the set of NVUs is relatively weak for the case with agonist
induced where only the Ca(2+) in cells inside the activated area becomes
oscillatory however, the radii of vessels both inside and outside the activated
area oscillate (albeit small for those outside). In addition the oscillation
profile differs between coupled and decoupled states with the time required to
refill the cytosol with decreasing Ca(2+) and increasing frequency with coupling.
The solution algorithm is shown to have excellent weak and strong scaling.
Results have been generated for tissue slices containing up to 4096 blocks.
PMID- 26441620
TI - Modeling spontaneous activity across an excitable epithelium: Support for a
coordination scenario of early neural evolution.
AB - Internal coordination models hold that early nervous systems evolved in the first
place to coordinate internal activity at a multicellular level, most notably the
use of multicellular contractility as an effector for motility. A recent example
of such a model, the skin brain thesis, suggests that excitable epithelia using
chemical signaling are a potential candidate as a nervous system precursor. We
developed a computational model and a measure for whole body coordination to
investigate the coordinative properties of such excitable epithelia. Using this
measure we show that excitable epithelia can spontaneously exhibit body-scale
patterns of activation. Relevant factors determining the extent of patterning are
the noise level for exocytosis, relative body dimensions, and body size. In
smaller bodies whole-body coordination emerges from cellular excitability and
bidirectional excitatory transmission alone. Our results show that basic internal
coordination as proposed by the skin brain thesis could have arisen in this
potential nervous system precursor, supporting that this configuration may have
played a role as a proto-neural system and requires further investigation.
PMID- 26441621
TI - Is predictive coding theory articulated enough to be testable?
PMID- 26441622
TI - Volterra representation enables modeling of complex synaptic nonlinear dynamics
in large-scale simulations.
AB - Chemical synapses are comprised of a wide collection of intricate signaling
pathways involving complex dynamics. These mechanisms are often reduced to simple
spikes or exponential representations in order to enable computer simulations at
higher spatial levels of complexity. However, these representations cannot
capture important nonlinear dynamics found in synaptic transmission. Here, we
propose an input-output (IO) synapse model capable of generating complex
nonlinear dynamics while maintaining low computational complexity. This IO
synapse model is an extension of a detailed mechanistic glutamatergic synapse
model capable of capturing the input-output relationships of the mechanistic
model using the Volterra functional power series. We demonstrate that the IO
synapse model is able to successfully track the nonlinear dynamics of the synapse
up to the third order with high accuracy. We also evaluate the accuracy of the IO
synapse model at different input frequencies and compared its performance with
that of kinetic models in compartmental neuron models. Our results demonstrate
that the IO synapse model is capable of efficiently replicating complex nonlinear
dynamics that were represented in the original mechanistic model and provide a
method to replicate complex and diverse synaptic transmission within neuron
network simulations.
PMID- 26441623
TI - Thalamic neuron models encode stimulus information by burst-size modulation.
AB - Thalamic neurons have been long assumed to fire in tonic mode during perceptive
states, and in burst mode during sleep and unconsciousness. However, recent
evidence suggests that bursts may also be relevant in the encoding of sensory
information. Here, we explore the neural code of such thalamic bursts. In order
to assess whether the burst code is generic or whether it depends on the detailed
properties of each bursting neuron, we analyzed two neuron models incorporating
different levels of biological detail. One of the models contained no information
of the biophysical processes entailed in spike generation, and described neuron
activity at a phenomenological level. The second model represented the evolution
of the individual ionic conductances involved in spiking and bursting, and
required a large number of parameters. We analyzed the models' input selectivity
using reverse correlation methods and information theory. We found that n-spike
bursts from both models transmit information by modulating their spike count in
response to changes to instantaneous input features, such as slope, phase,
amplitude, etc. The stimulus feature that is most efficiently encoded by bursts,
however, need not coincide with one of such classical features. We therefore
searched for the optimal feature among all those that could be expressed as a
linear transformation of the time-dependent input current. We found that bursting
neurons transmitted 6 times more information about such more general features.
The relevant events in the stimulus were located in a time window spanning ~100
ms before and ~20 ms after burst onset. Most importantly, the neural code
employed by the simple and the biologically realistic models was largely the
same, implying that the simple thalamic neuron model contains the essential
ingredients that account for the computational properties of the thalamic burst
code. Thus, our results suggest the n-spike burst code is a general property of
thalamic neurons.
PMID- 26441624
TI - A predictive model of muscle excitations based on muscle modularity for a large
repertoire of human locomotion conditions.
AB - Humans can efficiently walk across a large variety of terrains and locomotion
conditions with little or no mental effort. It has been hypothesized that the
nervous system simplifies neuromuscular control by using muscle synergies, thus
organizing multi-muscle activity into a small number of coordinative co
activation modules. In the present study we investigated how muscle modularity is
structured across a large repertoire of locomotion conditions including five
different speeds and five different ground elevations. For this we have used the
non-negative matrix factorization technique in order to explain EMG experimental
data with a low-dimensional set of four motor components. In this context each
motor components is composed of a non-negative factor and the associated muscle
weightings. Furthermore, we have investigated if the proposed descriptive
analysis of muscle modularity could be translated into a predictive model that
could: (1) Estimate how motor components modulate across locomotion speeds and
ground elevations. This implies not only estimating the non-negative factors
temporal characteristics, but also the associated muscle weighting variations.
(2) Estimate how the resulting muscle excitations modulate across novel
locomotion conditions and subjects. The results showed three major distinctive
features of muscle modularity: (1) the number of motor components was preserved
across all locomotion conditions, (2) the non-negative factors were consistent in
shape and timing across all locomotion conditions, and (3) the muscle weightings
were modulated as distinctive functions of locomotion speed and ground elevation.
Results also showed that the developed predictive model was able to reproduce
well the muscle modularity of un-modeled data, i.e., novel subjects and
conditions. Muscle weightings were reconstructed with a cross-correlation factor
greater than 70% and a root mean square error less than 0.10. Furthermore, the
generated muscle excitations matched well the experimental excitation with a
cross-correlation factor greater than 85% and a root mean square error less than
0.09. The ability of synthetizing the neuromuscular mechanisms underlying human
locomotion across a variety of locomotion conditions will enable solutions in the
field of neurorehabilitation technologies and control of bipedal artificial
systems. Open-access of the model implementation is provided for further analysis
at https://simtk.org/home/p-mep/.
PMID- 26441625
TI - Leg mechanics contribute to establishing swing phase trajectories during memory
guided stepping movements in walking cats: a computational analysis.
AB - When quadrupeds stop walking after stepping over a barrier with their forelegs,
the memory of barrier height and location is retained for many minutes. This
memory is subsequently used to guide hind leg movements over the barrier when
walking is resumed. The upslope of the initial trajectory of hind leg paw
movements is strongly dependent on the initial location of the paw relative to
the barrier. In this study, we have attempted to determine whether mechanical
factors contribute significantly in establishing the slope of the paw
trajectories by creating a four-link biomechanical model of a cat hind leg and
driving this model with a variety of joint-torque profiles, including average
torques for a range of initial paw positions relative to the barrier. Torque
profiles for individual steps were determined by an inverse dynamic analysis of
leg movements in three normal cats. Our study demonstrates that limb mechanics
can contribute to establishing the dependency of trajectory slope on the initial
position of the paw relative to the barrier. However, an additional contribution
of neuronal motor commands was indicated by the fact that the simulated slopes of
paw trajectories were significantly less than the observed slopes. A neuronal
contribution to the modification of paw trajectories was also revealed by our
observations that both the magnitudes of knee flexor muscle EMG bursts and the
initial knee flexion torques depended on initial paw position. Previous studies
have shown that a shift in paw position prior to stepping over a barrier changes
the paw trajectory to be appropriate for the new paw position. Our data indicate
that both mechanical and neuronal factors contribute to this updating process,
and that any shift in leg position during the delay period modifies the working
memory of barrier location.
PMID- 26441626
TI - Dynamic trajectory of multiple single-unit activity during working memory task in
rats.
AB - Working memory plays an important role in complex cognitive tasks. A popular
theoretical view is that transient properties of neuronal dynamics underlie
cognitive processing. The question raised here as to how the transient dynamics
evolve in working memory. To address this issue, we investigated the multiple
single-unit activity dynamics in rat medial prefrontal cortex (mPFC) during a Y
maze working memory task. The approach worked by reconstructing state space from
delays of the original single-unit firing rate variables, which were further
analyzed using kernel principal component analysis (KPCA). Then the neural
trajectories were obtained to visualize the multiple single-unit activity.
Furthermore, the maximal Lyapunov exponent (MLE) was calculated to quantitatively
evaluate the neural trajectories during the working memory task. The results
showed that the neuronal activity produced stable and reproducible neural
trajectories in the correct trials while showed irregular trajectories in the
incorrect trials, which may establish a link between the neurocognitive process
and behavioral performance in working memory. The MLEs significantly increased
during working memory in the correctly performed trials, indicating an increased
divergence of the neural trajectories. In the incorrect trials, the MLEs were
nearly zero and remained unchanged during the task. Taken together, the trial
specific neural trajectory provides an effective way to track the instantaneous
state of the neuronal population during the working memory task and offers
valuable insights into working memory function. The MLE describes the changes of
neural dynamics in working memory and may reflect different neuronal population
states in working memory.
PMID- 26441628
TI - A unified framework for spiking and gap-junction interactions in distributed
neuronal network simulations.
AB - Contemporary simulators for networks of point and few-compartment model neurons
come with a plethora of ready-to-use neuron and synapse models and support
complex network topologies. Recent technological advancements have broadened the
spectrum of application further to the efficient simulation of brain-scale
networks on supercomputers. In distributed network simulations the amount of
spike data that accrues per millisecond and process is typically low, such that a
common optimization strategy is to communicate spikes at relatively long
intervals, where the upper limit is given by the shortest synaptic transmission
delay in the network. This approach is well-suited for simulations that employ
only chemical synapses but it has so far impeded the incorporation of gap
junction models, which require instantaneous neuronal interactions. Here, we
present a numerical algorithm based on a waveform-relaxation technique which
allows for network simulations with gap junctions in a way that is compatible
with the delayed communication strategy. Using a reference implementation in the
NEST simulator, we demonstrate that the algorithm and the required data
structures can be smoothly integrated with existing code such that they
complement the infrastructure for spiking connections. To show that the unified
framework for gap-junction and spiking interactions achieves high performance and
delivers high accuracy in the presence of gap junctions, we present benchmarks
for workstations, clusters, and supercomputers. Finally, we discuss limitations
of the novel technology.
PMID- 26441627
TI - The basal ganglia select the expected sensory input used for predictive coding.
AB - While considerable evidence supports the notion that lower-level interpretation
of incoming sensory information is guided by top-down sensory expectations, less
is known about the source of the sensory expectations or the mechanisms by which
they are spread. Predictive coding theory proposes that sensory expectations flow
down from higher-level association areas to lower-level sensory cortex. A
separate theory of the role of prediction in cognition describes "emulations" as
linked representations of potential actions and their associated expected
sensation that are hypothesized to play an important role in many aspects of
cognition. The expected sensations in active emulations are proposed to be the
top-down expectation used in predictive coding. Representations of the potential
action and expected sensation in emulations are claimed to be instantiated in
distributed cortical networks. Combining predictive coding with emulations thus
provides a theoretical link between the top-down expectations that guide sensory
expectations and the cortical networks representing potential actions. Now moving
to theories of action selection, the basal ganglia has long been proposed to
select between potential actions by reducing inhibition to the cortical network
instantiating the desired action plan. Integration of these isolated theories
leads to the novel hypothesis that reduction in inhibition from the basal ganglia
selects not just action plans, but entire emulations, including the sensory input
expected to result from the action. Basal ganglia disinhibition is hypothesized
to both initiate an action and also allow propagation of the action's associated
sensory expectation down towards primary sensory cortex. This is a novel proposal
for the role of the basal ganglia in biasing perception by selecting the expected
sensation, and initiating the top-down transmission of those expectations in
predictive coding.
PMID- 26441629
TI - Distributed recurrent neural forward models with synaptic adaptation and CPG
based control for complex behaviors of walking robots.
AB - Walking animals, like stick insects, cockroaches or ants, demonstrate a
fascinating range of locomotive abilities and complex behaviors. The locomotive
behaviors can consist of a variety of walking patterns along with adaptation that
allow the animals to deal with changes in environmental conditions, like uneven
terrains, gaps, obstacles etc. Biological study has revealed that such complex
behaviors are a result of a combination of biomechanics and neural mechanism thus
representing the true nature of embodied interactions. While the biomechanics
helps maintain flexibility and sustain a variety of movements, the neural
mechanisms generate movements while making appropriate predictions crucial for
achieving adaptation. Such predictions or planning ahead can be achieved by way
of internal models that are grounded in the overall behavior of the animal.
Inspired by these findings, we present here, an artificial bio-inspired walking
system which effectively combines biomechanics (in terms of the body and leg
structures) with the underlying neural mechanisms. The neural mechanisms consist
of (1) central pattern generator based control for generating basic rhythmic
patterns and coordinated movements, (2) distributed (at each leg) recurrent
neural network based adaptive forward models with efference copies as internal
models for sensory predictions and instantaneous state estimations, and (3)
searching and elevation control for adapting the movement of an individual leg to
deal with different environmental conditions. Using simulations we show that this
bio-inspired approach with adaptive internal models allows the walking robot to
perform complex locomotive behaviors as observed in insects, including walking on
undulated terrains, crossing large gaps, leg damage adaptations, as well as
climbing over high obstacles. Furthermore, we demonstrate that the newly
developed recurrent network based approach to online forward models outperforms
the adaptive neuron forward models, which have hitherto been the state of the
art, to model a subset of similar walking behaviors in walking robots.
PMID- 26441630
TI - Editorial: Brain cholinergic mechanisms.
PMID- 26441631
TI - The evolutionary origin of the need to sleep: an inevitable consequence of
synaptic neurotransmission?
AB - It is proposed that the evolutionary origin of the need to sleep is the removal
of neurotransmitters (NTs) that escape reuptake and accumulate in brain
interstitial fluid (ISF). Recent work suggests that the activity of ionotropic
postsynaptic receptors, rapidly initiated by binding of NTs to extracellular
sites, is modulated over longer times by adsorption of these NTs to the lipid
bilayers in which the receptors are embedded. This bilayer-mediated mechanism is
far less molecularly specific than binding, so bilayer adsorption of NTs that
have diffused into synapses for other receptors would modulate their activity as
well. Although NTs are recycled by membrane protein reuptake, the process is less
than 100% efficient; a fraction escapes the region in which these specific
reuptake proteins are localized and eventually diffuses throughout the ISF. It is
estimated that even if only 0.1% of NTs escape reuptake, they would accumulate
and adsorb to bilayers in synapses of other receptors sufficiently to affect
receptor activity, the harmful consequences of which are avoided by sleep: a
period of efficient convective clearance of solutes together with greatly reduced
synaptic activity.
PMID- 26441632
TI - Co-release of glutamate and GABA from single vesicles in GABAergic neurons
exogenously expressing VGLUT3.
AB - The identity of the vesicle neurotransmitter transporter expressed by a neuron
largely corresponds with the primary neurotransmitter that cell releases.
However, the vesicular glutamate transporter subtype 3 (VGLUT3) is mainly
expressed in non-glutamatergic neurons, including cholinergic, serotonergic, or
GABAergic neurons. Though a functional role for glutamate release from these non
glutamatergic neurons has been demonstrated, the interplay between VGLUT3 and the
neuron's characteristic neurotransmitter transporter, particularly in the case of
GABAergic neurons, at the synaptic and vesicular level is less clear. In this
study, we explore how exogenous expression of VGLUT3 in striatal GABAergic
neurons affects the packaging and release of glutamate and GABA in synaptic
vesicles (SVs). We found that VGLUT3 expression in isolated, autaptic GABAergic
neurons leads to action potential evoked release of glutamate. Under these
conditions, glutamate and GABA could be packaged together in single vesicles
release either spontaneously or asynchronously. However, the presence of
glutamate in GABAergic vesicles did not affect uptake of GABA itself, suggesting
a lack of synergy in vesicle filling for these transmitters. Finally, we found
postsynaptic detection of glutamate released from GABAergic terminals difficult
when bona fide glutamatergic synapses were present, suggesting that co-released
glutamate cannot induce postsynaptic glutamate receptor clustering.
PMID- 26441633
TI - Measuring sleep quality in older adults: a comparison using subjective and
objective methods.
AB - Sleep quality decreases with aging and thus sleep complaints are prevalent in
older adults, particularly for those with cognitive impairment and dementia. For
older adults, emerging evidence suggests poor sleep quality increases risk of
developing cognitive impairment and dementia. Given the aging population-and the
impending economic burden associated with increasing numbers of dementia patients
there is pressing need to improve sleep quality among older adults. As such,
research efforts have increased focus on investigating the association between
age-related sleep changes and cognitive decline in older adults. Sleep quality is
a complex construct to evaluate empirically, and yet the Pittsburg Sleep Quality
Index (PSQI) is commonly used in studies as their only measure of sleep quality.
Furthermore, the PSQI may not be the best sleep quality measure for older adults,
due to its reliance on the cognitive capacity to reflect on the past month.
Further study is needed to determine the PSQI's validity among older adults.
Thus, the current study examined sleep quality for 78 community dwelling adults
55+ to determine the PSQI's predictive validity for objective sleep quality (as
measured by actigraphy). We compared two subjective measures of sleep quality-the
PSQI and Consensus Sleep Diary (CSD)-with actigraphy (MotionWatch 8(c);
camntech). Our results suggest perceived sleep quality is quite different from
objective reality, at least for adults 55+. Importantly, we show this difference
is unrelated to age, gender, education, or cognitive status (assessed using
standard screens). Previous studies have shown the PSQI to be a valuable tool for
assessing subjective sleep quality; however, our findings indicate for older
adults the PSQI should not be used as a substitute for actigraphy, or vice versa.
Hence, we conclude best practice is to include both subjective and objective
measures when examining sleep quality in older adults (i.e., the PSQI, CSD, and
actigraphy).
PMID- 26441634
TI - Exergaming as a Viable Therapeutic Tool to Improve Static and Dynamic Balance
among Older Adults and People with Idiopathic Parkinson's Disease: A Systematic
Review and Meta-Analysis.
AB - The use of virtual reality games (known as "exergaming") as a neurorehabilitation
tool is gaining interest. Therefore, we aim to collate evidence for the effects
of exergaming on the balance and postural control of older adults and people with
idiopathic Parkinson's disease (IPD). Six electronic databases were searched,
from inception to April 2015, to identify relevant studies. Standardized mean
differences (SMDs) and 95% confidence intervals (CI) were used to calculate
effect sizes between experimental and control groups. I (2) statistics were used
to determine levels of heterogeneity. 325 older adults and 56 people with IPD who
were assessed across 11 -studies. The results showed that exergaming improved
static balance (SMD 1.069, 95% CI 0.563-1.576), postural control (SMD 0.826, 95%
CI 0.481-1.170), and dynamic balance (SMD -0.808, 95% CI -1.192 to -0.424) in
healthy older adults. Two IPD studies showed an improvement in static balance
(SMD 0.124, 95% CI -0.581 to 0.828) and postural control (SMD 2.576, 95% CI 1.534
3.599). Our findings suggest that exergaming might be an appropriate therapeutic
tool for improving balance and postural control in older adults, but more -large
scale trials are needed to determine if the same is true for people with IPD.
PMID- 26441635
TI - Association of Pancreatic Polypeptide with Mild Cognitive Impairment Varies by
APOE epsilon4 Allele.
AB - We conducted a preliminary case-control investigation of the association of
pancreatic polypeptide (PP) with mild cognitive impairment (MCI) in 202 MCI cases
(mean age, 81.6 years) and 202 age- and sex-matched cognitively normal controls
in the Mayo Clinic Study of Aging. Plasma PP was measured and examined as the
natural logarithm (continuous) and dichotomized at the median. The OR (95% CI) of
MCI increased with increasing PP [1.46 (1.04-2.05)]. There was a negative
interaction of PP with apolipoprotein E (APOE) epsilon4 allele; compared to the
reference group (no APOE epsilon4 allele and low PP), the OR (95% CI) for
combinations of epsilon4 and PP were: 2.64 (1.39-5.04) for APOE epsilon4 plus low
PP; 2.09 (1.27-3.45) for no APOE epsilon4 plus high PP; and 1.91 (1.04-3.53) for
no APOE epsilon4 plus high PP (P for interaction = 0.017). There was also a trend
toward a negative interaction with type 2 diabetes (P for interaction = 0.058).
Compared to no diabetes and low PP, the OR (95% CI) was 3.02 (1.22-7.46) for low
PP plus diabetes but 1.80 (1.01-3.22) for high PP plus diabetes. Participants
with high PP had a greater mean (SD) weight loss (kilograms per decade) than
persons with low PP [-2.27 (4.07) vs. -1.61 (5.24); P = 0.016]. MCI cases had a
non-significantly greater weight loss per decade compared to controls. These
findings suggest that high PP alone or jointly with APOE epsilon4 allele or type
2 diabetes is associated with MCI, and that high PP may mitigate some effects of
APOE epsilon4 allele and type 2 diabetes on cognition. Potential mechanisms may
involve PP-related weight loss and centrally mediated effects of PP on cognition.
These findings remain to be validated in other studies.
PMID- 26441636
TI - Sex Differences in Stroke Subtypes, Severity, Risk Factors, and Outcomes among
Elderly Patients with Acute Ischemic Stroke.
AB - BACKGROUND: Although the age-specific incidence and mortality of stroke is higher
among men, stroke has a greater clinical effect on women. However, the sex
differences in stroke among elderly patients are unknown. Therefore, we aimed to
assess the sex differences in stroke among elderly stroke patients. METHODS:
Between 2005 and 2013, we recruited 1484 consecutive acute ischemic stroke (AIS)
patients (>=75 years old) from a specialized neurology hospital in Tianjin,
China. Information regarding their stroke subtypes, severity, risk factors, and
outcomes at 3 and 12 months after stroke were recorded. RESULTS: Comparing with
men, women had a significantly higher prevalence of severe stroke (17.20 vs.
12.54%), hypertension (76.42 vs. 66.39%), dyslipidemias (30.35 vs. 22.76%), and
obesity (18.40 vs. 9.32%), P < 0.05. Comparing with women, men had a
significantly higher prevalence of intracranial artery stenosis (23.11 vs.
17.45%), current smoking (29.60 vs. 13.05%), and alcohol consumption (12.15 vs.
0.47%), P < 0.05. Moreover, dependency was more common among women at 3 and 12
months after stroke, although the sex difference disappeared after adjusting for
stroke subtypes, severity, and risk factors. CONCLUSION: Elderly women with AIS
had more severe stroke status and worse outcomes at 3 and 12 months after stroke.
Thus, elderly female post-AIS patients are a crucial population that should be
assisted with controlling their risk factors for stroke and changing their
lifestyle.
PMID- 26441637
TI - Oxytocin modulates meta-mood as a function of age and sex.
AB - Attending to and understanding one's own feelings are components of meta-mood and
constitute important socio-affective skills across the entire lifespan. Growing
evidence suggests a modulatory role of the neuropeptide oxytocin on various socio
affective processes. Going beyond previous work that almost exclusively examined
young men and perceptions of emotions in others, the current study investigated
effects of intranasal oxytocin on meta-mood in young and older men and women. In
a double-blind between-group design, participants were randomly assigned to self
administer either intranasal oxytocin or a placebo before responding to items
from the Trait Meta-Mood Scale (TMMS) about attention to feelings and clarity of
feelings. In contrast to older women, oxytocin relative to placebo increased
attention to feelings in older men. Oxytocin relative to placebo enhanced meta
mood in young female participants but reduced it in older female participants.
This pattern of findings supports an age- and sex-differential modulatory
function of the neuropeptide oxytocin on meta-mood, possibly associated with
neurobiological differences with age and sex.
PMID- 26441638
TI - Switching between hands in a serial reaction time task: a comparison between
young and old adults.
AB - Healthy aging is associated with a variety of functional and structural brain
alterations. These age-related brain alterations have been assumed to negatively
impact cognitive and motor performance. Especially important for the execution of
everyday activities in older adults (OA) is the ability to perform movements that
depend on both hands working together. However, bimanual coordination is
typically deteriorated with increasing age. Hence, a deeper understanding of such
age-related brain-behavior alterations might offer the opportunity to design
future interventional studies in order to delay or even prevent the decline in
cognitive and/or motor performance over the lifespan. Here, we examined to what
extent the capability to acquire and maintain a novel bimanual motor skill is
still preserved in healthy OA as compared to their younger peers (YA). For this
purpose, we investigated performance of OA (n = 26) and YA (n = 26) in a bimanual
serial reaction time task (B-SRTT), on two experimental sessions, separated by 1
week. We found that even though OA were generally slower in global response
times, they showed preserved learning capabilities in the B-SRTT. However,
sequence specific learning was more pronounced in YA as compared to OA.
Furthermore, we found that switching between hands during B-SRTT learning trials
resulted in increased response times (hand switch costs), a phenomenon that was
more pronounced in OA. These hand switch costs were reduced in both groups over
the time course of learning. More interestingly, there were no group differences
in hand switch costs on the second training session. These results provide novel
evidence that bimanual motor skill learning is capable of reducing age-related
deficits in hand switch costs, a finding that might have important implications
to prevent the age-related decline in sensorimotor function.
PMID- 26441639
TI - Regional electroencephalogram (EEG) alpha power and asymmetry in older adults: a
study of short-term test-retest reliability.
AB - Although regional alpha power and asymmetry measures have been widely used as
indices of individual differences in emotional processing and affective style in
younger populations, there have been relatively few studies that have examined
these measures in older adults. Here, we examined the short-term test-retest
reliability of resting regional alpha power (7.5-12.5 Hz) and asymmetry in a
sample of 38 active, community-dwelling older adults (M age = 71.2, SD = 6.5
years). Resting electroencephalogram recordings were made before and after a
perceptual computer task. Pearson and intra-class correlations indicated
acceptable test-retest reliability for alpha power and asymmetry measures in all
regions. Interestingly, alpha asymmetry appeared to be less affected by the task
than was alpha power. Findings suggest that alpha asymmetry may reflect more
enduring, "trait-like" characteristics, while alpha power may reflect more "state
like" processes in older adults.
PMID- 26441640
TI - Environmental enrichment does not influence hypersynchronous network activity in
the Tg2576 mouse model of Alzheimer's disease.
AB - The cognitive reserve hypothesis claims that the brain can overcome pathology by
reinforcing preexistent processes or by developing alternative cognitive
strategies. Epidemiological studies have revealed that this reserve can be built
throughout life experiences as education or leisure activities. We previously
showed that an early transient environmental enrichment (EE) durably improves
memory performances in the Tg2576 mouse model of Alzheimer's disease (AD).
Recently, we evidenced a hypersynchronous brain network activity in young adult
Tg2576 mice. As aberrant oscillatory activity can contribute to memory deficits,
we wondered whether the long-lasting memory improvements observed after EE were
associated with a reduction of neuronal network hypersynchrony. Thus, we exposed
non-transgenic (NTg) and Tg2576 mice to standard or enriched housing conditions
for 10 weeks, starting at 3 months of age. Two weeks after EE period, Tg2576 mice
presented similar seizure susceptibility to a GABA receptor antagonist.
Immediately after and 2 weeks after this enrichment period, standard and enriched
housed Tg2576 mice did not differ with regards to the frequency of interictal
spikes on their electroencephalographic (EEG) recordings. Thus, the long-lasting
effect of this EE protocol on memory capacities in Tg2576 mice is not mediated by
a reduction of their cerebral aberrant neuronal activity at early ages.
PMID- 26441642
TI - Commentary: Duration-dependent effects of the BDNF Val66Met polymorphism on
anodal tDCS induced motor cortex plasticity in older adults: a group and
individual perspective.
PMID- 26441641
TI - The impact of aging on the spatial accuracy of quick corrective arm movements in
response to sudden target displacement during reaching.
AB - Age-related declines in visuomotor processing speed can have a large impact on
motor performance in elderly individuals. Contrary to previous findings, however,
recent studies revealed that elderly individuals are able to quickly react to
displacement of a visual target during reaching. Here, we investigated the
influence of aging on quick, corrective responses to perturbations during
reaching in the terms of their functional contribution to accuracy. Elderly and
young adults performed reaching movements to a visual target that could be
displaced during reaching, and they were requested to move their hand to reach
the final target location as quickly as possible. Results showed that, for the
younger group, the variance in the directional error of the corrective response
correlated with the variance in the reaching trajectory at the halfway point of
the reach, but the correlation decreased at the end of the reaching. On the other
hand, such correlations were not significant in elderly participants, although
the variance of the directional error did not show a significant difference
between age groups. Thus, the quick, corrective response seems to play an
important role in decreasing variability, especially before the end of reaching,
and aging can impair this process.
PMID- 26441643
TI - Basal Forebrain Atrophy Contributes to Allocentric Navigation Impairment in
Alzheimer's Disease Patients.
AB - The basal forebrain degenerates in Alzheimer's disease (AD) and this process is
believed to contribute to the cognitive decline observed in AD patients.
Impairment in spatial navigation is an early feature of the disease but whether
basal forebrain dysfunction in AD is responsible for the impaired navigation
skills of AD patients is not known. Our objective was to investigate the
relationship between basal forebrain volume and performance in real space as well
as computer-based navigation paradigms in an elderly cohort comprising
cognitively normal controls, subjects with amnestic mild cognitive impairment and
those with AD. We also tested whether basal forebrain volume could predict the
participants' ability to perform allocentric- vs. egocentric-based navigation
tasks. The basal forebrain volume was calculated from 1.5 T magnetic resonance
imaging (MRI) scans, and navigation skills were assessed using the human analog
of the Morris water maze employing allocentric, egocentric, and mixed
allo/egocentric real space as well as computerized tests. When considering the
entire sample, we found that basal forebrain volume correlated with spatial
accuracy in allocentric (cued) and mixed allo/egocentric navigation tasks but not
the egocentric (uncued) task, demonstrating an important role of the basal
forebrain in mediating cue-based spatial navigation capacity. Regression analysis
revealed that, although hippocampal volume reflected navigation performance
across the entire sample, basal forebrain volume contributed to mixed
allo/egocentric navigation performance in the AD group, whereas hippocampal
volume did not. This suggests that atrophy of the basal forebrain contributes to
aspects of navigation impairment in AD that are independent of hippocampal
atrophy.
PMID- 26441644
TI - Unexploited opportunities for phage therapy.
PMID- 26441645
TI - The ever unfolding story of cAMP signaling in trypanosomatids: vive la
difference!
AB - Kinetoplastids are unicellular, eukaryotic, flagellated protozoans containing the
eponymous kinetoplast. Within this order, the family of trypanosomatids are
responsible for some of the most serious human diseases, including Chagas disease
(Trypanosoma cruzi), sleeping sickness (Trypanosoma brucei spp.), and
leishmaniasis (Leishmania spp). Although cAMP is produced during the life cycle
stages of these parasites, its signaling pathways are very different from those
of mammals. The absence of G-protein-coupled receptors, the presence of
structurally different adenylyl cyclases, the paucity of known cAMP effector
proteins and the stringent need for regulation of cAMP in the small kinetoplastid
cells all suggest a significantly different biochemical pathway and likely cell
biology. However, each of the main kinetoplastid parasites express four class 1
type cyclic nucleotide-specific phosphodiesterases (PDEA-D), which have highly
similar catalytic domains to that of human PDEs. To date, only TbrPDEB, expressed
as two slightly different isoforms TbrPDEB1 and B2, has been found to be
essential when ablated. Although the genomes contain reasonably well conserved
genes for catalytic and regulatory domains of protein kinase A, these have been
shown to have varied structural and functional roles in the different species.
Recent discovery of a role of cAMP/AMP metabolism in a quorum-sensing signaling
pathway in T. brucei, and the identification of downstream cAMP Response Proteins
(CARPs) whose expression levels correlate with sensitivity to PDE inhibitors,
suggests a complex signaling cascade. The interplay between the roles of these
novel CARPs and the quorum-sensing signaling pathway on cell division and
differentiation makes for intriguing cell biology and a new paradigm in cAMP
signal transduction, as well as potential targets for trypanosomatid-specific
cAMP pathway-based therapeutics.
PMID- 26441646
TI - Advances in optical imaging for pharmacological studies.
AB - Imaging approaches are an essential tool for following up over time
representative parameters of in vivo models, providing useful information in
pharmacological studies. Main advantages of optical imaging approaches compared
to other imaging methods are their safety, straight-forward use and cost
effectiveness. A main drawback, however, is having to deal with the presence of
high scattering and high absorption in living tissues. Depending on how these
issues are addressed, three different modalities can be differentiated: planar
imaging (including fluorescence and bioluminescence in vivo imaging), optical
tomography, and optoacoustic approaches. In this review we describe the latest
advances in optical in vivo imaging with pharmacological applications, with
special focus on the development of new optical imaging probes in order to
overcome the strong absorption introduced by different tissue components,
especially hemoglobin, and the development of multimodal imaging systems in order
to overcome the resolution limitations imposed by scattering.
PMID- 26441647
TI - Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and
potential template for novel pharmacotherapeutic agents in neuropsychiatric
disorders.
AB - Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant
Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor
(KOPr) agonist, and thus implicates the KOPr system and its endogenous agonist
ligands (the dynorphins) in higher functions, including cognition and perceptual
effects. Salvinorin A is the only selective KOPr ligand to be widely available
outside research or medical settings, and salvinorin A-containing products have
undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known
to be powerful counter-modulatory mechanisms to dopaminergic function, which is
important in mood and reward engendered by natural and chemical reinforcers
(including drugs of abuse). KOPr activation (including by salvinorin A) can thus
cause aversion and anhedonia in preclinical models. Salvinorin A is also a
completely new scaffold for medicinal chemistry approaches, since it is a non
nitrogenous neoclerodane, unlike other known opioid ligands. Ongoing efforts have
the goal of discovering novel semi-synthetic salvinorin analogs with potential
KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased
agonist effects), with a reduced burden of undesirable effects associated with
salvinorin A.
PMID- 26441648
TI - Cellular imaging: a key phenotypic screening strategy for predictive toxicology.
AB - Incorporating phenotypic screening as a key strategy enhances predictivity and
translatability of drug discovery efforts. Cellular imaging serves as a
"phenotypic anchor" to identify important toxicologic pathology that encompasses
an array of underlying mechanisms, thus provides an effective means to reduce
drug development failures due to insufficient safety. This mini-review highlights
the latest advances in hepatotoxicity, cardiotoxicity, and genetic toxicity tests
that utilized cellular imaging as a screening strategy, and recommends path
forward for further improvement.
PMID- 26441650
TI - When cure becomes an illness-abuse of addictive prescription medicines.
PMID- 26441651
TI - An update on the Pharmacovigilance Programme of India.
PMID- 26441649
TI - Targeting protein-protein interactions in complexes organized by A kinase
anchoring proteins.
AB - Cyclic AMP is a ubiquitous intracellular second messenger involved in the
regulation of a wide variety of cellular processes, a majority of which act
through the cAMP - protein kinase A (PKA) signaling pathway and involve PKA
phosphorylation of specific substrates. PKA phosphorylation events are typically
spatially restricted and temporally well controlled. A-kinase anchoring proteins
(AKAPs) directly bind PKA and recruit it to specific subcellular loci targeting
the kinase activity toward particular substrates, and thereby provide discrete
spatiotemporal control of downstream phosphorylation events. AKAPs also scaffold
other signaling molecules into multi-protein complexes that function as
crossroads between different signaling pathways. Targeting AKAP coordinated
protein complexes with high-affinity peptidomimetics or small molecules to tease
apart distinct protein-protein interactions (PPIs) therefore offers important
means to disrupt binding of specific components of the complex to better
understand the molecular mechanisms involved in the function of individual
signalosomes and their pathophysiological role. Furthermore, development of novel
classes of small molecules involved in displacement of AKAP-bound signal
molecules is now emerging. Here, we will focus on mechanisms for targeting PPI,
disruptors that modulate downstream cAMP signaling and their role, especially in
the heart.
PMID- 26441652
TI - Acylated flavonol glycosides from Tagetes minuta with antibacterial activity.
AB - Wild marigold (Tagetes minuta), a flowering plant of the family Asteraceae
contains compounds of pharmaceutical and nutritional importance especially
essential oils and flavonols. Identification, characterization of flavonols and
determination of their antibacterial activity were major objectives of the
current study. The isolation and purification of flavonols was accomplished using
chromatographic techniques while structural elucidation was completed by LC-MS
and NMR spectroscopy. The extracts and purified compounds were tested against
various bacterial strains for antibacterial activity. A total of 19 flavonols
were isolated from this species. Of these, 17 were of butanol and two of ethyl
acetate extracts. Based on the concentration and purity, eight potential
flavonols were selected and structurally elucidated. Four flavonols, 6
hydroxyquercetin 7-O-beta-(6''-galloylglucopyranoside; 2), 6-hydroxykaempferol 7
O-beta-glucopyranoside (5), 6-hydroxykaempferol 7-O-beta-(6''
galloylglucopyranoside; 7), 6-hydroxyquercetin 7-O-beta-(6''
caffeoylglucopyranoside; 9), were identified for the first time from T. minuta.
Butanol and ethyl acetate extracts of flowers and seeds showed significant
antibacterial activity against Micrococcus leteus, Staphylococcus aureus,
Bacillus subtilis, and Pseudomonas pikettii. Among the isolated flavonols only 1,
2, and 18 were found to possess significant antibacterial activity against M.
luteus. The extracts and purified flavonols from T. minuta can be potential
candidates for antibacterial drug discovery and support to ethnopharmacological
use.
PMID- 26441653
TI - Genetically-encoded tools for cAMP probing and modulation in living systems.
AB - Intracellular 3'-5'-cyclic adenosine monophosphate (cAMP) is one of the principal
second messengers downstream of a manifold of signal transduction pathways,
including the ones triggered by G protein-coupled receptors. Not surprisingly,
biochemical assays for cAMP have been instrumental for basic research and drug
discovery for decades, providing insights into cellular physiology and guiding
pharmaceutical industry. However, despite impressive track record, the majority
of conventional biochemical tools for cAMP probing share the same fundamental
shortcoming-all the measurements require sample disruption for cAMP liberation.
This common bottleneck, together with inherently low spatial resolution of
measurements (as cAMP is typically analyzed in lysates of thousands of cells),
underpin the ensuing limitations of the conventional cAMP assays: (1) genuine
kinetic measurements of cAMP levels over time in a single given sample are
unfeasible; (2) inability to obtain precise information on cAMP spatial
distribution and transfer at subcellular levels, let alone the attempts to
pinpoint dynamic interactions of cAMP and its effectors. At the same time,
tremendous progress in synthetic biology over the recent years culminated in
drastic refinement of our toolbox, allowing us not only to bypass the limitations
of conventional assays, but to put intracellular cAMP life-span under tight
control-something, that seemed scarcely attainable before. In this review article
we discuss the main classes of modern genetically-encoded tools tailored for cAMP
probing and modulation in living systems. We examine the capabilities and
weaknesses of these different tools in the context of their operational
characteristics and applicability to various experimental set-ups involving
living cells, providing the guidance for rational selection of the best tools for
particular needs.
PMID- 26441655
TI - Assessing the synergy between cholinomimetics and memantine as augmentation
therapy in cognitive impairment in schizophrenia. A virtual human patient trial
using quantitative systems pharmacology.
AB - While many drug discovery research programs aim to develop highly selective
clinical candidates, their clinical success is limited because of the complex non
linear interactions of human brain neuronal circuits. Therefore, a rational
approach for identifying appropriate synergistic multipharmacology and validating
optimal target combinations is desperately needed. A mechanism-based Quantitative
Systems Pharmacology (QSP) computer-based modeling platform that combines
biophysically realistic preclinical neurophysiology and neuropharmacology with
clinical information is a possible solution. This paper reports the application
of such a model for Cognitive Impairment In Schizophrenia (CIAS), where the
cholinomimetics galantamine and donepezil are combined with memantine and with
different antipsychotics and smoking in a virtual human patient experiment. The
results suggest that cholinomimetics added to antipsychotics have a modest effect
on cognition in CIAS in non-smoking patients with haloperidol and risperidone and
to a lesser extent with olanzapine and aripiprazole. Smoking reduces the effect
of cholinomimetics with aripiprazole and olanzapine, but enhances the effect in
haloperidol and risperidone. Adding memantine to antipsychotics improves
cognition except with quetiapine, an effect enhanced with smoking. Combining
cholinomimetics, antipsychotics and memantine in general shows an additive
effect, except for a negative interaction with aripiprazole and quetiapine and a
synergistic effect with olanzapine and haloperidol in non-smokers and haloperidol
in smokers. The complex interaction of cholinomimetics with memantine,
antipsychotics and smoking can be quantitatively studied using mechanism-based
advanced computer modeling. QSP modeling of virtual human patients can possibly
generate useful insights on the non-linear interactions of multipharmacology
drugs and support complex CNS R&D projects in cognition in search of synergistic
polypharmacy.
PMID- 26441654
TI - Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug
delivery.
AB - Ultrasound (US) is one of the most frequently used diagnostic methods. It is a
non-invasive, comparably inexpensive imaging method with a broad spectrum of
applications, which can be increased even more by using bubbles as contrast
agents (CAs). There are various different types of bubbles: filled with different
gases, composed of soft- or hard-shell materials, and ranging in size from nano-
to micrometers. These intravascular CAs enable functional analyses, e.g., to
acquire organ perfusion in real-time. Molecular analyses are achieved by coupling
specific ligands to the bubbles' shell, which bind to marker molecules in the
area of interest. Bubbles can also be loaded with or attached to drugs, peptides
or genes and can be destroyed by US pulses to locally release the entrapped
agent. Recent studies show that US CAs are also valuable tools in hyperthermia
induced ablation therapy of tumors, or can increase cellular uptake of locally
released drugs by enhancing membrane permeability. This review summarizes
important steps in the development of US CAs and introduces the current clinical
applications of contrast-enhanced US. Additionally, an overview of the recent
developments in US probe design for functional and molecular diagnosis as well as
for drug delivery is given.
PMID- 26441656
TI - Systems pharmacology of adiposity reveals inhibition of EP300 as a common
therapeutic mechanism of caloric restriction and resveratrol for obesity.
AB - Both caloric restriction (CR) and resveratrol (RSV) have beneficial effects on
obesity. However, the biochemical pathways that mediate these beneficial effects
might be complex and interconnected and have not been fully elucidated. To reveal
the common therapeutic mechanism of CR and RSV, we performed a comparative
transcriptome analysis of adipose tissues from diet-induced obese (DIO) zebrafish
and obese humans. We identified nine genes in DIO zebrafish and seven genes in
obese humans whose expressions were regulated by CR and RSV. Although the gene
lists did not overlap except for one gene, the gene ontologies enriched in the
gene lists were highly overlapped, and included genes involved in adipocyte
differentiation, lipid storage and lipid metabolism. Bioinformatic analysis of
cis-regulatory sequences of these genes revealed that their transcriptional
regulators also overlapped, including EP300, HDAC2, CEBPB, CEBPD, FOXA1, and
FOXA2. We also identified 15 and 46 genes that were dysregulated in the adipose
tissue of DIO zebrafish and obese humans, respectively. Bioinformatics analysis
identified EP300, HDAC2, and CEBPB as common transcriptional regulators for these
genes. EP300 is a histone and lysyl acetyltransferase that modulates the function
of histone and various proteins including CEBPB, CEBPD, FOXA1, and FOXA2. We
demonstrated that adiposity in larval zebrafish was significantly reduced by
C646, an inhibitor of EP300 that antagonizes acetyl-CoA. The reduction of
adiposity by C646 was not significantly different from that induced by RSV or co
treatment of C646 and RSV. These results indicate that the inhibition of EP300
might be a common therapeutic mechanism between CR and RSV in adipose tissues of
obese individuals.
PMID- 26441657
TI - 5-HT6 receptor agonism facilitates emotional learning.
AB - Serotonin (5-HT) and its receptors play crucial roles in various aspects of mood
and cognitive functions. However, the role of specific 5-HT receptors in these
processes remains to be better understood. Here, we examined the effects of the
selective and potent 5-HT6 agonist (WAY208466) on mood, anxiety and emotional
learning in mice. Male C57Bl/6J mice were therefore tested in the forced swim
test (FST), elevated plus-maze (EPM), and passive avoidance tests (PA),
respectively. In a dose-response experiment, mice were treated intraperitoneally
with WAY208466 at 3, 9, or 27 mg/kg and examined in an open field arena open
field test (OFT) followed by the FST. 9 mg/kg of WAY208466 reduced immobility in
the FST, without impairing the locomotion. Thus, the dose of 9 mg/kg was
subsequently used for tests of anxiety and emotional learning. There was no
significant effect of WAY208466 in the EPM. In the PA, mice were trained 30 min
before the treatment with saline or WAY208466. Two separate sets of animals were
used for short term memory (tested 1 h post-training) or long term memory (tested
24 h post-training). WAY208466 improved both short and long term memories,
evaluated by the latency to enter the dark compartment, in the PA. The WAY208466
treated animals also showed more grooming and rearing in the light compartment.
To better understand the molecular mechanisms and brain regions involved in the
facilitation of emotional learning by WAY208466, we studied its effects on signal
transduction and immediate early gene expression. WAY208466 increased the levels
of phospho-Ser(845)-GluA1 and phospho-Ser(217/221)-MEK in the caudate-putamen.
Levels of phospho-Thr(202/204)-Erk1/2 and the ratio mature BDNF/proBDNF were
increased in the hippocampus. Moreover, WAY208466 increased c-fos in the
hippocampus and Arc expression in both hippocampus and prefrontal cortex (PFC).
The results indicate antidepressant efficacy and facilitation of emotional
learning by 5-HT6 receptor agonism via mechanisms that promote neuronal
plasticity in caudate putamen, hippocampus, and PFC.
PMID- 26441658
TI - Agonist and antagonist effects of tobacco-related nitrosamines on human
alpha4beta2 nicotinic acetylcholine receptors.
AB - Regulation of the "neuronal" nicotinic acetylcholine receptors (nAChRs) is
implicated in both tobacco addiction and smoking-dependent tumor promotion. Some
of these effects are caused by the tobacco-derived N-nitrosamines, which are
carcinogenic compounds that avidly bind to nAChRs. However, the functional
effects of these drugs on specific nAChR subtypes are largely unknown. By using
patch-clamp methods, we tested 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone
(NNK) and N'-nitrosonornicotine (NNN) on human alpha4beta2 nAChRs. These latter
are widely distributed in the mammalian brain and are also frequently expressed
outside the nervous system. NNK behaved as a partial agonist, with an apparent
EC50 of 16.7 MUM. At 100 MUM, it activated 16% of the maximal current activated
by nicotine. When NNK was co-applied with nicotine, it potentiated the currents
elicited by nicotine concentrations <= 100 nM. At higher concentrations of
nicotine, NNK always inhibited the alpha4beta2 nAChR. In contrast, NNN was a pure
inhibitor of this nAChR subtype, with IC50 of approximately 1 nM in the presence
of 10 MUM nicotine. The effects of both NNK and NNN were mainly competitive and
largely independent of Vm. The different actions of NNN and NNK must be taken
into account when interpreting their biological effects in vitro and in vivo.
PMID- 26441659
TI - Spatiotemporal regulation of cAMP signaling controls the human trophoblast
fusion.
AB - During human placentation, mononuclear cytotrophoblasts fuse to form
multinucleated syncytia ensuring hormonal production and nutrient exchanges
between the maternal and fetal circulation. Syncytial formation is essential for
the maintenance of pregnancy and for fetal growth. The cAMP signaling pathway is
the major route to trigger trophoblast fusion and its activation results in
phosphorylation of specific intracellular target proteins, in transcription of
fusogenic genes and assembly of macromolecular protein complexes constituting the
fusogenic machinery at the plasma membrane. Specificity in cAMP signaling is
ensured by generation of localized pools of cAMP controlled by cAMP
phosphodiesterases (PDEs) and by discrete spatial and temporal activation of
protein kinase A (PKA) in supramolecular signaling clusters inside the cell
organized by A-kinase-anchoring proteins (AKAPs) and by organization of signal
termination by protein phosphatases (PPs). Here we present original observations
on the available components of the cAMP signaling pathway in the human placenta
including PKA, PDE, and PP isoforms as well as AKAPs. We continue to discuss the
current knowledge of the spatiotemporal regulation of cAMP signaling triggering
trophoblast fusion.
PMID- 26441660
TI - Sensorimotor gating impairments induced by MK-801 treatment may be reduced by
tolerance effect and by familiarization in monkeys.
AB - Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces
schizophreniclike effects. It is therefore widely used in experimental models of
schizophrenia including prepulse inhibition (PPI) impairments in rodents.
Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order
to evaluate MK-801 effects on monkeys' PPI, we tested eight capuchin monkeys
(Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg).
Results show PPI impairment in acute administration of the highest dose (0.03
mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI
test throughout treatment trials, in contrast with rodent studies. These results
indicate that tolerance effect and familiarization with PPI test may reduce the
sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug
training interaction.
PMID- 26441661
TI - Multi-target pharmacology: possibilities and limitations of the "skeleton key
approach" from a medicinal chemist perspective.
AB - Multi-target drugs have raised considerable interest in the last decade owing to
their advantages in the treatment of complex diseases and health conditions
linked to drug resistance issues. Prospective drug repositioning to treat
comorbid conditions is an additional, overlooked application of multi-target
ligands. While medicinal chemists usually rely on some version of the lock and
key paradigm to design novel therapeutics, modern pharmacology recognizes that
the mid- and long-term effects of a given drug on a biological system may depend
not only on the specific ligand-target recognition events but also on the
influence of the repeated administration of a drug on the cell gene signature.
The design of multi-target agents usually imposes challenging restrictions on the
topology or flexibility of the candidate drugs, which are briefly discussed in
the present article. Finally, computational strategies to approach the
identification of novel multi-target agents are overviewed.
PMID- 26441663
TI - Insights to ligand binding to the monoamine transporters-from homology modeling
to LeuBAT and dDAT.
AB - Understanding of drug binding to the human biogenic amine transporters (BATs) is
essential to explain the mechanism of action of these pharmaceuticals but more
importantly to be able to develop new and improved compounds to be used in the
treatment of depression or drug addiction. Until recently no high resolution
structure was available of the BATs and homology modeling was a necessity.
Various studies have revealed experimentally validated binding modes of numerous
ligands to the BATs using homology modeling. Here we examine and discuss the
similarities between the binding models of substrates, antidepressants,
psychostimulants, and mazindol in homology models of the human BATs and the
recently published crystal structures of the Drosophila dopamine transporter and
the engineered protein, LeuBAT. The comparison reveals that careful computational
modeling combined with experimental data can be utilized to predict binding of
molecules to proteins that agree very well with crystal structures.
PMID- 26441662
TI - A review on mitochondrial restorative mechanism of antioxidants in Alzheimer's
disease and other neurological conditions.
AB - Neurodegenerative diseases are intricate in nature because of the involvement of
the multiple pathophysiological events including mitochondrial dysfunction,
neuroinflammation and oxidative stress. Alzheimer's disease (AD) is a
neurodegenerative disease explained by extracellular amyloid beta deposits,
intracellular neurofibrillary tangles and mitochondrial dysfunction. Increasing
evidence has indicated that mitochondrial dysfunction displays significant role
in the pathophysiological processes of AD. Mitochondrial dysfunction involves
alterations in mitochondrial respiratory enzyme complex activities, oxidative
stress, opening of permeability transition pore, and enhanced apoptosis. Various
bioenergetics and antioxidants have been tried or under different investigational
phase against AD and other neurodegenerative disorders (Parkinson's disease,
Huntington's disease, and Amyotrophic lateral sclerosis) because of their complex
and multiple site of action. These mitochondrial-targeting bioenergetics and
antioxidant compounds such as coenzyme Q10, idebenone, creatine, mitoQ, mitovitE,
MitoTEMPOL, latrepirdine, methylene blue, triterpenoids, SS peptides, curcumin,
Ginkgo biloba, and omega-3 polyunsaturated fatty acids with potential efficacy in
AD have been identified. Present review is intent to discuss mitochondrial
restorative mechanisms of these bioenergetics and antioxidants as a potential
alternative drug strategy for effective management of AD.
PMID- 26441664
TI - Developing multi-target therapeutics to fine-tune the evolutionary dynamics of
the cancer ecosystem.
PMID- 26441665
TI - Different pH-sensitivity patterns of 30 sodium channel inhibitors suggest
chemically different pools along the access pathway.
AB - The major drug binding site of sodium channels is inaccessible from the
extracellular side, drug molecules can only access it either from the membrane
phase, or from the intracellular aqueous phase. For this reason, ligand-membrane
interactions are as important determinants of inhibitor properties, as ligand
protein interactions. One-way to probe this is to modify the pH of the
extracellular fluid, which alters the ratio of charged vs. uncharged forms of
some compounds, thereby changing their interaction with the membrane. In this
electrophysiology study we used three different pH values: 6.0, 7.3, and 8.6 to
test the significance of the protonation-deprotonation equilibrium in drug access
and affinity. We investigated drugs of several different indications:
carbamazepine, lamotrigine, phenytoin, lidocaine, bupivacaine, mexiletine,
flecainide, ranolazine, riluzole, memantine, ritanserin, tolperisone,
silperisone, ambroxol, haloperidol, chlorpromazine, clozapine, fluoxetine,
sertraline, paroxetine, amitriptyline, imipramine, desipramine, maprotiline,
nisoxetine, mianserin, mirtazapine, venlafaxine, nefazodone, and trazodone. We
recorded the pH-dependence of potency, reversibility, as well as onset/offset
kinetics. As expected, we observed a strong correlation between the acidic
dissociation constant (pKa) of drugs and the pH-dependence of their potency.
Unexpectedly, however, the pH-dependence of reversibility or kinetics showed
diverse patterns, not simple correlation. Our data are best explained by a model
where drug molecules can be trapped in at least two chemically different
environments: A hydrophilic trap (which may be the aqueous cavity within the
inner vestibule), which favors polar and less lipophilic compounds, and a
lipophilic trap (which may be the membrane phase itself, and/or lipophilic
binding sites on the channel). Rescue from the hydrophilic and lipophilic traps
can be promoted by alkalic and acidic extracellular pH, respectively.
PMID- 26441666
TI - Decreased expression of alpha-2-HS glycoprotein in the sera of rats treated with
Eurycoma longifolia extract.
AB - Eurycoma longifolia is a Malaysian native herb that has been widely used as an
aphrodisiac and a remedy for andropause. Although the physiological effects of
the plant extract were predicted as a result of the alterations in protein
expression, the key protein(s) involved in these alterations are still unclear.
In the present study, we have investigated the effect of standardized E.
longifolia extract on serum protein expression up to 28 days following oral
administration in rats. Serum protein profiles were analyzed by 2-dimensional
electrophoresis, and altered proteins were identified via mass spectrometry. We
observed that alpha-2-HS glycoprotein (AHS) was significantly decreased in the
serum of experimentally treated rats compared to pre-treated animals. Moreover,
reduction in AHS was confirmed using competitive enzyme-linked immunosorbent
assay. AHS expression is known to be associated with insulin resistance and
diabetes. Our data indicated that serum AHS was reduced in rats treated with
standardized E. longifolia extract, and therefore form a prelude for further
investigation into the effects of this natural extract in animal models involving
infertility and diabetes.
PMID- 26441667
TI - Corrigendum: Impact of kinase activating and inactivating patient mutations on
binary PKA interactions.
AB - [This corrects the article on p. 170 in vol. 6, PMID: 26347651.].
PMID- 26441668
TI - Revisiting the mitogenetic effect of ultra-weak photon emission.
AB - This paper reviews the 90 years long controversial history of the so-called
"mitogenetic radiation," the first case of non-chemical distant interactions,
reported by Gurwitsch (1923). It was soon described as ultraweak UV, emitted by a
number of biological systems, and stimulating mitosis in "competent" (in this
sense) cells. In the following 20 years this phenomenon attracted enormous
interest of the scientific community, and gave rise to more than 700 publications
around the world. Yet, this wave of research vanished after several ostensibly
disproving works in late 1930-s, and was not resumed later, regardless of quite
serious grounds for that. The authors discuss separately two aspects of the
problem: (1) do living organisms emit ultraweak radiation in the UV range
(irrespective of whether it has any biological role), and (2) are there any real
effects of this ultraweak photon emission (UPE) upon cell division and/or other
biological functions? Analysis of the available data permits to conclude, that UV
fraction of UPE should be regarded real, while its biological effects are
difficult to reproduce. This causes a paradox. A number of presently known
qualities of UPE were initially discovered (predicted?) by the "early workers" on
the basis of biological effects. Yet the qualities they discovered were proved
later (the UV component of UPE, the sources of UPE among biological systems,
etc...), while the biological effect they used for UPE "detection" remains
questionable. Importance of this area for basic biology and medicine, and
potential usefulness of UPE as a non-invasive research method, invite scientists
to attack this problem again, applying powerful research facilities of modern
science. Yet, because of complexity and uncertainty of the problem, further
progress in this area demands comprehensive examination of both positive and
negative works, with particular attention to their methodical details.
PMID- 26441669
TI - TRPA1 mediates amplified sympathetic responsiveness to activation of
metabolically sensitive muscle afferents in rats with femoral artery occlusion.
AB - Autonomic responses to activation of mechanically and metabolically sensitive
muscle afferent nerves during static contraction are augmented in rats with
femoral artery occlusion. Moreover, metabolically sensitive transient receptor
potential cation channel subfamily A, member 1 (TRPA1) has been reported to
contribute to sympathetic nerve activity (SNA) and arterial blood pressure (BP)
responses evoked by static muscle contraction. Thus, in the present study, we
examined the mechanisms by which afferent nerves' TRPA1 plays a role in
regulating amplified sympathetic responsiveness due to a restriction of blood
flow directed to the hindlimb muscles. Our data show that 24-72 h of femoral
artery occlusion (1) upregulates the protein levels of TRPA1 in dorsal root
ganglion (DRG) tissues; (2) selectively increases expression of TRPA1 in DRG
neurons supplying metabolically sensitive afferent nerves of C-fiber (group IV);
and (3) enhances renal SNA and BP responses to AITC (a TRPA1 agonist) injected
into the hindlimb muscles. In addition, our data demonstrate that blocking TRPA1
attenuates SNA and BP responses during muscle contraction to a greater degree in
ligated rats than those responses in control rats. In contrast, blocking TRPA1
fails to attenuate SNA and BP responses during passive tendon stretch in both
groups. Overall, results of this study indicate that alternations in muscle
afferent nerves' TRPA1 likely contribute to enhanced sympathetically mediated
autonomic responses via the metabolic component of the muscle reflex under
circumstances of chronic muscle ischemia.
PMID- 26441671
TI - Databases for multilevel biophysiology research available at Physiome.jp.
AB - Physiome.jp (http://physiome.jp) is a portal site inaugurated in 2007 to support
model-based research in physiome and systems biology. At Physiome.jp, several
tools and databases are available to support construction of physiological, multi
hierarchical, large-scale models. There are three databases in Physiome.jp,
housing mathematical models, morphological data, and time-series data. In late
2013, the site was fully renovated, and in May 2015, new functions were
implemented to provide information infrastructure to support collaborative
activities for developing models and performing simulations within the database
framework. This article describes updates to the databases implemented since
2013, including cooperation among the three databases, interactive model
browsing, user management, version management of models, management of parameter
sets, and interoperability with applications.
PMID- 26441670
TI - Bridging scales through multiscale modeling: a case study on protein kinase A.
AB - The goal of multiscale modeling in biology is to use structurally based physico
chemical models to integrate across temporal and spatial scales of biology and
thereby improve mechanistic understanding of, for example, how a single mutation
can alter organism-scale phenotypes. This approach may also inform therapeutic
strategies or identify candidate drug targets that might otherwise have been
overlooked. However, in many cases, it remains unclear how best to synthesize
information obtained from various scales and analysis approaches, such as
atomistic molecular models, Markov state models (MSM), subcellular network
models, and whole cell models. In this paper, we use protein kinase A (PKA)
activation as a case study to explore how computational methods that model
different physical scales can complement each other and integrate into an
improved multiscale representation of the biological mechanisms. Using measured
crystal structures, we show how molecular dynamics (MD) simulations coupled with
atomic-scale MSMs can provide conformations for Brownian dynamics (BD)
simulations to feed transitional states and kinetic parameters into protein-scale
MSMs. We discuss how milestoning can give reaction probabilities and forward-rate
constants of cAMP association events by seamlessly integrating MD and BD
simulation scales. These rate constants coupled with MSMs provide a robust
representation of the free energy landscape, enabling access to kinetic, and
thermodynamic parameters unavailable from current experimental data. These
approaches have helped to illuminate the cooperative nature of PKA activation in
response to distinct cAMP binding events. Collectively, this approach exemplifies
a general strategy for multiscale model development that is applicable to a wide
range of biological problems.
PMID- 26441672
TI - Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice.
AB - Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease in which
weakness, increased susceptibility to muscle injury, and inadequate repair appear
to underlie the pathology. While most attention has focused within the muscle
fiber, we recently demonstrated in mdx mice (murine model for DMD) significant
morphologic alterations at the motor endplate of the neuromuscular junction (NMJ)
and corresponding NMJ transmission failure after injury. Here we extend these
initial observations at the motor endplate to gain insight into the pre- vs.
postsynaptic morphology, as well as the subsynaptic nuclei in healthy (WT) vs.
mdx mice. We quantified the discontinuity and branching of the terminal nerve in
adult mice. We report mdx- and age-dependent changes for discontinuity and an
increase in branching when compared to WT. To examine mdx- and age-dependent
changes in the relative localization of pre- and postsynaptic structures, we
calculated NMJ occupancy, defined as the ratio of the footprint occupied by
presynaptic vesicles vs. that of the underlying motor endplate. The normally
congruent coupling between presynaptic and postsynaptic morphology was altered in
mdx mice, independent of age. Finally we found an almost two-fold increase in the
number of nuclei and an increase in density (nuclei/area) underlying the NMJ.
These outcomes suggest substantial remodeling of the NMJ during dystrophic
progression. This remodeling reflects plasticity in both pre- and postsynaptic
contributors to NMJ structure, and thus perhaps also NM transmission and muscle
function.
PMID- 26441673
TI - Caloric restriction induces energy-sparing alterations in skeletal muscle
contraction, fiber composition and local thyroid hormone metabolism that persist
during catch-up fat upon refeeding.
AB - Weight regain after caloric restriction results in accelerated fat storage in
adipose tissue. This catch-up fat phenomenon is postulated to result partly from
suppressed skeletal muscle thermogenesis, but the underlying mechanisms are
elusive. We investigated whether the reduced rate of skeletal muscle contraction
relaxation cycle that occurs after caloric restriction persists during weight
recovery and could contribute to catch-up fat. Using a rat model of
semistarvation-refeeding, in which fat recovery is driven by suppressed
thermogenesis, we show that contraction and relaxation of leg muscles are slower
after both semistarvation and refeeding. These effects are associated with (i)
higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri
iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type
2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and
(iii) accumulation of slow fibers at the expense of fast fibers. These
semistarvation-induced changes persisted during recovery and correlated with
impaired expression of transcription factors involved in slow-twitch muscle
development. We conclude that diminished muscle thermogenesis following caloric
restriction results from reduced muscle T3 levels, alteration in muscle-specific
transcription factors, and fast-to-slow fiber shift causing slower contractility.
These energy-sparing effects persist during weight recovery and contribute to
catch-up fat.
PMID- 26441674
TI - A multiscale computational model of spatially resolved calcium cycling in cardiac
myocytes: from detailed cleft dynamics to the whole cell concentration profiles.
AB - Mathematical modeling of excitation-contraction coupling (ECC) in ventricular
cardiac myocytes is a multiscale problem, and it is therefore difficult to
develop spatially detailed simulation tools. ECC involves gradients on the length
scale of 100 nm in dyadic spaces and concentration profiles along the 100 MUm of
the whole cell, as well as the sub-millisecond time scale of local concentration
changes and the change of lumenal Ca(2+) content within tens of seconds. Our
concept for a multiscale mathematical model of Ca(2+) -induced Ca(2+) release
(CICR) and whole cardiomyocyte electrophysiology incorporates stochastic
simulation of individual LC- and RyR-channels, spatially detailed concentration
dynamics in dyadic clefts, rabbit membrane potential dynamics, and a system of
partial differential equations for myoplasmic and lumenal free Ca(2+) and Ca(2+)
binding molecules in the bulk of the cell. We developed a novel computational
approach to resolve the concentration gradients from dyadic space to cell level
by using a quasistatic approximation within the dyad and finite element methods
for integrating the partial differential equations. We show whole cell Ca(2+)
concentration profiles using three previously published RyR-channel Markov
schemes.
PMID- 26441675
TI - Comparison of swimming capacity and energetics of migratory European eel
(Anguilla anguilla) and New Zealand short-finned eel (A. australis).
AB - The spawning migration of the European eel (Anguilla anguilla) can cover more
than 6000 km, while that of the New Zealand short-finned eel (A. australis) is
assumed to be approximately 3000 km. Since these species are expected to show
adaptive traits to such an important lifetime event, we hypothesized differences
in swimming capacity and energetics as a response to this adaptation. In an
experimental swimming respirometer set-up, critical swimming speed (Ucrit),
optimal swimming speed (Uopt), mass specific oxygen consumption rate (MO2),
standard metabolic rate (SMR), active metabolic rate at Ucrit (AMRcrit) and at
Uopt (AMRopt), the minimum cost of transport at Uopt (COTmin), and the scope for
activity, were assessed and compared between the species. With a similar body
length and mass, European eels showed ca. 25% higher values for both Ucrit and
Uopt, and 23% lower values for COTmin, compared to New Zealand short-finned eels.
However, SMR, AMRcrit, AMRopt, and scope for activity did not differ between the
species, indicating very similar swimming physiology traits. This study discusses
physiological aspects of long distance migration and provides recommendations for
(a) swimming respirometry in anguilliform fish, and (b) telemetry research using
externally attached pop-up tags.
PMID- 26441676
TI - Designing and testing regenerative pulp treatment strategies: modeling the
transdentinal transport mechanisms.
AB - The need for simulation models to thoroughly test the inflammatory effects of
dental materials and dentinogenic effects of specific signaling molecules has
been well recognized in current dental research. The development of a model that
simulates the transdentinal flow and the mass transfer mechanisms is of prime
importance in terms of achieving the objectives of developing more effective
treatment modalities in restorative dentistry. The present protocol study is part
of an ongoing investigation on the development of a methodology that can
calculate the transport rate of selected molecules inside a typical dentinal
tubule. The transport rate of biological molecules has been investigated using a
validated CFD code. In that framework we propose a simple algorithm that, given
the type of molecules of the therapeutic agent and the maximum acceptable time
for the drug concentration to attain a required value at the pulpal side of the
tubules, can estimate the initial concentration to be imposed.
PMID- 26441677
TI - Cardiac autonomic responses after resistance exercise in treated hypertensive
subjects.
AB - The aim of this study was to assess and to compare heart rate variability (HRV)
after resistance exercise (RE) in treated hypertensive and normotensive subjects.
Nine hypertensive men [HT: 58.0 +/- 7.7 years, systolic blood pressure (SBP) =
133.6 +/- 6.5 mmHg, diastolic blood pressure (DBP) = 87.3 +/- 8.1 mmHg; under
antihypertensive treatment] and 11 normotensive men (NT: 57.1 +/- 6.0 years, SBP
= 127 +/- 8.5 mmHg, DBP = 82.7 +/- 5.5 mmHg) performed a single session of RE (2
sets of 15-20 repetitions, 50% of 1 RM, 120 s interval between sets/exercise) for
the following exercises: leg extension, leg press, leg curl, bench press, seated
row, triceps push-down, seated calf flexion, seated arm curl. HRV was assessed at
resting and during 10 min of recovery period by calculating time (SDNN, RMSSD,
pNN50) and frequency domain (LF, HF, LF/HF) indices. Mean values of HRV indices
were reduced in the post-exercise period compared to the resting period (HT:
lnHF: 4.7 +/- 1.4 vs. 2.4 +/- 1.2 ms(2); NT: lnHF: 4.8 +/- 1.5 vs. 2.2 +/- 1.1
ms(2), p < 0.01). However, there was no group vs. time interaction in this
response (p = 0.8). The results indicate that HRV is equally suppressed after RE
in normotensive and hypertensive individuals. These findings suggest that a
single session of RE does not bring additional cardiac autonomic stress to
treated hypertensive subjects.
PMID- 26441679
TI - Neuro-mechanical determinants of repeated treadmill sprints - Usefulness of an
"hypoxic to normoxic recovery" approach.
AB - To improve our understanding of the limiting factors during repeated sprinting,
we manipulated hypoxia severity during an initial set and examined the effects on
performance and associated neuro-mechanical alterations during a subsequent set
performed in normoxia. On separate days, 13 active males performed eight 5-s
sprints (recovery = 25 s) on an instrumented treadmill in either normoxia near
sea-level (SL; FiO2 = 20.9%), moderate (MH; FiO2 = 16.8%) or severe normobaric
hypoxia (SH; FiO2 = 13.3%) followed, 6 min later, by four 5-s sprints (recovery =
25 s) in normoxia. Throughout the first set, along with distance covered [larger
sprint decrement score in SH (-8.2%) compared to SL (-5.3%) and MH (-7.2%); P <
0.05], changes in contact time, step frequency and root mean square activity
(surface electromyography) of the quadriceps (Rectus femoris muscle) in SH
exceeded those in SL and MH (P < 0.05). During first sprint of the subsequent
normoxic set, the distance covered (99.6, 96.4, and 98.3% of sprint 1 in SL, MH,
and SH, respectively), the main kinetic (mean vertical, horizontal, and resultant
forces) and kinematic (contact time and step frequency) variables as well as
surface electromyogram of quadriceps and plantar flexor muscles were fully
recovered, with no significant difference between conditions. Despite differing
hypoxic severity levels during sprints 1-8, performance and neuro-mechanical
patterns did not differ during the four sprints of the second set performed in
normoxia. In summary, under the circumstances of this study (participant
background, exercise-to-rest ratio, hypoxia exposure), sprint mechanical
performance and neural alterations were largely influenced by the hypoxia
severity in an initial set of repeated sprints. However, hypoxia had no residual
effect during a subsequent set performed in normoxia. Hence, the recovery of
performance and associated neuro-mechanical alterations was complete after
resting for 6 min near sea level, with a similar fatigue pattern across
conditions during subsequent repeated sprints in normoxia.
PMID- 26441680
TI - Analysis of the protein related receptor GPR92 in G-cells.
AB - A continuous assessment of ingested food in the gastric lumen is essential for
fine-tuning the digestive activities, including the secretion of the regulatory
hormones such as gastrin. It has been proposed that G-cells may be able to sense
the amount of ingested proteins and adjust the secretion of gastrin accordingly.
Our previous studies have shown that G-cells express suitable receptor types,
most notably the peptone-receptor GPR92 and the amino acid receptors GPRC6A and
CaSR; however, their relative importance remained unclear. To determine the
relative quantity of each receptor type, individual G-cells isolated from the
transgenic mouse line mGas-EGFP were analyzed by means of a Liquid Chromatography
Tandem-Mass Spectrometry (LC-MS/MS) procedure. The results indicate that the
relative amount of receptor protein for GPR92 was much higher than for the
receptor types GPRC6A and CaSR. These findings support the notion that the
peptone-receptor GPR92 may be particularly relevant for sensing partially
digested protein products. This view was supported by the finding that a high
protein diet affected the expression level of the peptone-receptor GPR92 in the
gastric antrum as well as in the circumvallate papillae.
PMID- 26441681
TI - Dual effect of lithium on NFAT5 activity in kidney cells.
AB - Lithium salts are used widely for treatment of bipolar and other mental
disorders. Lithium therapy is accompanied frequently by renal side effects, such
as nephrogenic diabetes insipidus or chronic kidney disease (CKD), but the
molecular mechanisms underlying these effects are still poorly understood. In the
present study we examined the effect of lithium on the activity of the
osmosensitive transcriptional activator nuclear factor of activated T cells 5
(NFAT5, also known as TonEBP), which plays a key role in renal cellular
osmoprotection and urinary concentrating ability. Interestingly, we found
different effects of lithium on NFAT5 activity, depending on medium osmolality
and incubation time. When cells were exposed to lithium for a relative short
period (24 h), NFAT5 activity was significantly increased, especially under
isosmotic conditions, resulting in an enhanced expression of the NFAT5 target
gene heat shock protein 70 (HSP70). Further analysis revealed that the increase
of NFAT5 activity depended primarily on an enhanced activity of the c-terminal
transactivation domain (TAD), while NFAT5 protein abundance was largely
unaffected. Enhanced activity of the TAD is probably mediated by lithium-induced
inhibitory phosphorylation of glycogen synthase kinase 3beta (GSK-3beta), which
is in accordance with previous studies. When cells were exposed to lithium for a
longer period (96 h), cellular NFAT5 activity and subsequently expression of
HSP70 significantly decreased under hyperosmotic conditions, due to diminished
NFAT5 protein abundance, also resulting from GSK-3beta inhibition. Taken
together, our results provide evidence that lithium has opposing effects on NFAT5
activity, depending on environmental osmolality and exposure duration. The
potential impacts of these observations on the diverse effects of lithium on
kidney function are discussed.
PMID- 26441682
TI - Stem cell origin differently affects bone tissue engineering strategies.
AB - Bone tissue engineering approaches are encouraging for the improvement of
conventional bone grafting technique drawbacks. Thanks to their self-renewal and
multi-lineage differentiation ability, stem cells are one of the major actors in
tissue engineering approaches, and among these adult mesenchymal stem cells
(MSCs) hold a great promise for regenerative medicine strategies. Bone marrow
MSCs (BM-MSCs) are the first- identified and well-recognized stem cell population
used in bone tissue engineering. Nevertheless, several factors hamper BM-MSC
clinical application and subsequently, new stem cell sources have been
investigated for these purposes. The fruitful selection and combination of tissue
engineered scaffold, progenitor cells, and physiologic signaling molecules
allowed the surgeon to reconstruct the missing natural tissue. On the basis of
these considerations, we analyzed the capability of two different scaffolds,
planned for osteochondral tissue regeneration, to modulate differentiation of
adult stem cells of dissimilar local sources (i.e., periodontal ligament,
maxillary periosteum) as well as adipose-derived stem cells (ASCs), in view of
possible craniofacial tissue engineering strategies. We demonstrated that cells
are differently committed toward the osteoblastic phenotype and therefore, taking
into account their specific features, they could be intriguing cell sources in
different stem cell-based bone/periodontal tissue regeneration approaches.
PMID- 26441678
TI - The similarity between N-terminal targeting signals for protein import into
different organelles and its evolutionary relevance.
AB - The proper distribution of proteins between the cytosol and various membrane
bound compartments is crucial for the functionality of eukaryotic cells. This
requires the cooperation between protein transport machineries that translocate
diverse proteins from the cytosol into these compartments and targeting signal(s)
encoded within the primary sequence of these proteins that define their cellular
destination. The mechanisms exerting protein translocation differ remarkably
between the compartments, but the predominant targeting signals for mitochondria,
chloroplasts and the ER share the N-terminal position, an alpha-helical
structural element and the removal from the core protein by intraorganellar
cleavage. Interestingly, similar properties have been described for the
peroxisomal targeting signal type 2 mediating the import of a fraction of soluble
peroxisomal proteins, whereas other peroxisomal matrix proteins encode the type 1
targeting signal residing at the extreme C-terminus. The structural similarity of
N-terminal targeting signals poses a challenge to the specificity of protein
transport, but allows the generation of ambiguous targeting signals that mediate
dual targeting of proteins into different compartments. Dual targeting might
represent an advantage for adaptation processes that involve a redistribution of
proteins, because it circumvents the hierarchy of targeting signals. Thus, the co
existence of two equally functional import pathways into peroxisomes might
reflect a balance between evolutionary constant and flexible transport routes.
PMID- 26441684
TI - Attentional Profiles and White Matter Correlates in Attention
Deficit/Hyperactivity Disorder Predominantly Inattentive Type.
AB - Attention-deficit/hyperactivity disorder (ADHD) is a widely studied
neurodevelopmental disorder. It is a highly heterogeneous condition, encompassing
different types of expression. The predominantly inattentive type is the most
prevalent and the most stable over the lifetime, yet it is the least-studied
presentation. To increase understanding of its cognitive profile, 29 children
with attention-deficit/hyperactivity disorder of predominantly inattentive type
(ADHD-I) and 29 matched controls, aged 7-15 years, had their attentional
abilities assessed through the Conners' continuous performance test. Diffusion
tensor imaging data were collected for all of the participants using a 3.0-T MRI
system. Fractional anisotropy (FA) values were obtained for 20 fiber tracts, and
brain-behavior correlations were calculated for 42 of the children. The ADHD-I
children differed significantly from the typically developing (TD) children with
respect to attentional measures, such as the ability to maintain response-time
consistency throughout the task (Hit RT SE and Variability), vigilance (Hit RT
ISI and Hit RT ISI SE), processing speed (Hit RT), selective attention
(Omissions), sustained attention (Hit RT Block Change), error profile (Response
Style), and inhibitory control (Perseverations). Evidence of significant
differences between the ADHD-I and the TD participants was not found with respect
to the mean FA values in the fiber tracts analyzed. Moderate and strong
correlations between performance on the attention indicators and the tract
average FA values were found for the ADHD-I group. Our results contribute to a
better characterization of the attentional profile of ADHD-I individuals and
suggest that in children and adolescents with ADHD-I, attentional performance is
mainly associated with the white matter structure of the long associative fibers
that connect anterior-posterior brain areas.
PMID- 26441683
TI - The Impact of Neuroimmune Alterations in Autism Spectrum Disorder.
AB - Autism spectrum disorder (ASD) involves a complex interplay of both genetic and
environmental risk factors, with immune alterations and synaptic connection
deficiency in early life. In the past decade, studies of ASD have substantially
increased, in both humans and animal models. Immunological imbalance (including
autoimmunity) has been proposed as a major etiological component in ASD, taking
into account increased levels of pro-inflammatory cytokines observed in
postmortem brain from patients, as well as autoantibody production. Also,
epidemiological studies have established a correlation of ASD with family history
of autoimmune diseases; associations with major histocompatibility complex
haplotypes and abnormal levels of immunological markers in the blood. Moreover,
the use of animal models to study ASD is providing increasing information on the
relationship between the immune system and the pathophysiology of ASD. Herein, we
will discuss the accumulating literature for ASD, giving special attention to the
relevant aspects of factors that may be related to the neuroimmune interface in
the development of ASD, including changes in neuroplasticity.
PMID- 26441685
TI - Assessing and Stabilizing Aberrant Neuroplasticity in Autism Spectrum Disorder:
The Potential Role of Transcranial Magnetic Stimulation.
AB - Exciting developments have taken place in the neuroscience research in autism
spectrum disorder (ASD), and results from these studies indicate that brain in
ASD is associated with aberrant neuroplasticity. Transcranial magnetic
stimulation (TMS) has rapidly evolved to become a widely used, safe, and non
invasive neuroscientific tool to investigate a variety of neurophysiological
processes, including neuroplasticity. The diagnostic and therapeutic potential of
TMS in ASD is beginning to be realized. In this article, we briefly reviewed
evidence of aberrant neuroplasticity in ASD, suggested future directions in
assessing neuroplasticity using repetitive TMS (rTMS), and discussed the
potential of rTMS in rectifying aberrant neuroplasticity in ASD.
PMID- 26441687
TI - Attention Deficit Hyperactivity Disorder in the Light of the Epigenetic Paradigm.
AB - Attention deficit hyperactivity disorder (ADHD) is a highly prevalent
neurodevelopmental disorder characterized by a definite behavioral pattern that
might lead to performance problems in the social, educational, or work
environments. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth
Edition, the symptoms of ADHD were restricted to those associated with cognitive
(attention deficit) and behavioral (hyperactivity/impulsivity) deficits, while
deficient emotional self-regulation, a relevant source of morbidity, was left
out. The etiology of it is complex, as its exact causes have not yet been fully
elucidated. ADHD seems to arise from a combination of various genetic and
environmental factors that alter the developing brain, resulting in structural
and functional abnormalities. The aim of this paper was to review epigenetics and
ADHD focused on how multidimensional mechanisms influence the behavioral
phenotype.
PMID- 26441686
TI - Cigarette Cravings, Impulsivity, and the Brain.
AB - Craving is a core feature of tobacco use disorder as well as a significant
predictor of smoking relapse. Studies have shown that appetitive smoking-related
stimuli (e.g., someone smoking) trigger significant cravings in smokers impede
their self-control capacities and promote drug seeking behavior. In this review,
we begin by an overview of functional magnetic resonance imaging (fMRI) studies
investigating the neural correlates of smokers to appetitive smoking cues. The
literature reveals a complex and vastly distributed neuronal network underlying
smokers' craving response that recruits regions involved in self-referential
processing, planning/regulatory processes, emotional responding, attentional
biases, and automatic conducts. We then selectively review important factors
contributing to the heterogeneity of results that significantly limit the
implications of these findings, namely between- (abstinence, smoking
expectancies, and self-regulation) and within-studies factors (severity of
smoking dependence, sex-differences, motivation to quit, and genetic factors).
Remarkably, we found that little to no attention has been devoted to examine the
influence of personality traits on the neural correlates of cigarette cravings in
fMRI studies. Impulsivity has been linked with craving and relapse in substance
and tobacco use, which prompted our research team to examine the influence of
impulsivity on cigarette cravings in an fMRI study. We found that the influence
of impulsivity on cigarette cravings was mediated by fronto-cingulate mechanisms.
Given the high prevalence of cigarette smoking in several psychiatric disorders
that are characterized by significant levels of impulsivity, we conclude by
identifying psychiatric patients as a target population whose tobacco-smoking
habits deserve further behavioral and neuro-imaging investigation.
PMID- 26441688
TI - Music and Sound in Time Processing of Children with ADHD.
AB - ADHD involves cognitive and behavioral aspects with impairments in many
environments of children and their families' lives. Music, with its playful,
spontaneous, affective, motivational, temporal, and rhythmic dimensions can be of
great help for studying the aspects of time processing in ADHD. In this article,
we studied time processing with simple sounds and music in children with ADHD
with the hypothesis that children with ADHD have a different performance when
compared with children with normal development in tasks of time estimation and
production. The main objective was to develop sound and musical tasks to evaluate
and correlate the performance of children with ADHD, with and without
methylphenidate, compared to a control group with typical development. The study
involved 36 participants of age 6-14 years, recruited at NANI-UNIFESP/SP,
subdivided into three groups with 12 children in each. Data was collected through
a musical keyboard using Logic Audio Software 9.0 on the computer that recorded
the participant's performance in the tasks. Tasks were divided into sections:
spontaneous time production, time estimation with simple sounds, and time
estimation with music. RESULTS: (1) performance of ADHD groups in temporal
estimation of simple sounds in short time intervals (30 ms) were statistically
lower than that of control group (p < 0.05); (2) in the task comparing musical
excerpts of the same duration (7 s), ADHD groups considered the tracks longer
when the musical notes had longer durations, while in the control group, the
duration was related to the density of musical notes in the track. The positive
average performance observed in the three groups in most tasks perhaps indicates
the possibility that music can, in some way, positively modulate the symptoms of
inattention in ADHD.
PMID- 26441689
TI - Game Theory Paradigm: A New Tool for Investigating Social Dysfunction in Major
Depressive Disorders.
AB - Social dysfunction is a prominent source of distress and disability in patients
with major depressive disorder (MDD) but is commonly omitted from current
clinical studies, although some researchers propose an evolutionary strategy to
understand these negative outcomes. Limited knowledge about the neural basis of
social dysfunction in MDD results from traditional paradigms, which lack insights
into social interactions. Game theoretical modeling offers a new tool for
investigating social-interaction impairments in neuropsychiatric disorders. This
review first introduces three widely used games from game theory and the major
behavioral and neuroimaging findings obtained using these games in healthy
populations. We also address the factors that modulate behaviors in games and
their neural bases. We then summarize the current findings obtained by using
these games in depressed patients and discuss the clinical implications of these
abnormal game behaviors. Finally, we briefly discuss future prospects that may
further elucidate the clinical use of a game theory paradigm in MDD.
PMID- 26441690
TI - Very-Brief, Web-Based Interventions for Reducing Alcohol Use and Related Problems
among College Students: A Review.
AB - Very-brief, web-based alcohol interventions have great potential due to their
convenience, ease of dissemination, and college students' stated preference for
this intervention modality. To address the efficacy of these interventions, we
conducted a review of the literature to identify randomized controlled trials
(RCTs). Fifteen published reports were included. All RCTs meeting criteria for
inclusion tested an intervention that featured personalized feedback on students'
patterns of alcohol consumption. This review found some evidence to support the
efficacy of very-brief, web-based interventions among college students for
alcohol use reduction. Several trials, however, reported no evidence of efficacy
and the methods of multiple trials raised concerns about potential bias that may
have influenced study results. By contrast, this review did not yield evidence to
support the efficacy of very-brief, web-based interventions for reduction of
alcohol--related problems among college students. We found evidence to support
the efficacy of two main types of intervention content: (a) focused solely on
personalized normative feedback designed to correct misconceptions about peer
alcohol consumption and (b) multi-component interventions. Future research is
needed to test enhancements to very-brief, web-based interventions that feature
personalized feedback on patterns of alcohol use and to determine for which types
of college drinkers (e.g., heavier or lighter drinkers) these interventions are
most efficacious. In addition, future studies are needed to test novel, very
brief, web-based interventions featuring approaches other than personalized
feedback. In summary, this review yielded some evidence supporting very-brief,
web-based interventions in reducing alcohol use but not related problems in
college students. Very-brief, web-based interventions are worth pursuing given
their convenience, privacy, and potential public health benefit.
PMID- 26441692
TI - The Impact on Family Functioning of Social Media Use by Depressed Adolescents: A
Qualitative Analysis of the Family Options Study.
AB - BACKGROUND: Adolescent depression is a prevalent mental health problem, which can
have a major impact on family cohesion. In such circumstances, excessive use of
the Internet by adolescents may exacerbate family conflict and lack of cohesion.
The current study aims to explore these patterns within an intervention study for
depressed adolescents. METHOD: The current study draws upon data collected from
parents within the family options randomized controlled trial that examined
family based interventions for adolescent depression (12-18 years old) in
Melbourne, Australia (2012-2014). Inclusion in the trial required adolescents to
meet diagnostic criteria for a major depressive disorder via the Structured
Clinical Interview for DSM-IV Childhood Disorders. The transcripts of sessions
were examined using qualitative thematic analysis. The transcribed sessions
consisted of 56 h of recordings in total from 39 parents who took part in the
interventions. RESULTS: The thematic analysis explored parental perceptions of
their adolescent's use of social media (SM) and access to Internet content,
focusing on the possible relationship between adolescent Internet use and the
adolescent's depressive disorder. Two overarching themes emerged as follows: the
sense of loss of parental control over the family environment and parents'
perceived inability to protect their adolescent from material encountered on the
Internet and social interactions via SM. CONCLUSION: Parents within the context
of family based treatments felt that prolonged exposure to SM exposed their
already vulnerable child to additional stressors and risks. The thematic analysis
uncovered a sense of parental despair and lack of control, which is consistent
with their perception of SM and the Internet as relentless and threatening to
their parental authority and family cohesion.
PMID- 26441691
TI - Examining the Role of Vasopressin in the Modulation of Parental and Sexual
Behaviors.
AB - Vasopressin (VP) and VP-like neuropeptides are evolutionarily stable peptides
found in all vertebrate species. In non-mammalian vertebrates, vasotocin (VT)
plays a role similar to mammalian VP, whereas mesotocin and isotocin are
functionally similar to mammalian oxytocin (OT). Here, we review the involvement
of VP in brain circuits, synaptic plasticity, evolution, and function,
highlighting the role of VP in social behavior. In all studied species, VP is
encoded on chromosome 20p13, and in mammals, VP is produced in specific
hypothalamic nuclei and released by the posterior pituitary. The role of VP is
mediated by the stimulation of the V1a, V1b, and V2 receptors as well as the
oxytocinergic and purinergic receptors. VT and VP functions are usually related
to osmotic and cardiovascular homeostasis when acting peripherally. However,
these neuropeptides are also critically involved in the central modulation of
social behavior displays, such as pairing recognition, pair-bonding, social
memory, sexual behavior, parental care, and maternal and aggressive behavior.
Evidence suggests that these effects are primarily mediated by V1a receptor in
specific brain circuits that provide important information for the onset and
control of social behaviors in normal and pathological conditions.
PMID- 26441693
TI - Ethnicity and Smoking-Associated DNA Methylation Changes at HIV Co-Receptor
GPR15.
AB - Smoking is associated with poorer health outcomes for both African and European
Americans. In order to better understand whether ethnic-specific genetic
variation may underlie some of these differences, we compared the smoking
associated genome-wide methylation signatures of African Americans with those of
European Americans, and followed up this analysis with a focused examination of
the most ethnically divergent locus, cg19859270, at the GPR15 gene. We examined
the association of methylation at this locus to the rs2230344 SNP and GPR15 gene
and protein expression. Consistent with prior analyses, AHRR residue cg05575921
was the most differentially methylated residue in both African Americans and
European Americans. However, the second most differentially methylated locus in
African Americans, cg19859270, was only modestly differentially methylated in
European Americans. Interrogation of the methylation status of this CpG residue
found in GPR15, a chemokine receptor involved in HIV pathogenesis, showed a
significant interaction of ethnicity with smoking as well as a marginal effect of
genotype at rs2230344, a neighboring non-synonymous SNP, but only among African
Americans. Gene and protein expression analyses showed that demethylation at
cg19859270 was associated with an increase in both mRNA and protein levels. Since
GPR15 is involved in the early stages of viral replication for some HIV-1 and HIV
2 isolates, and the prevalence of HIV is increased in African Americans and
smokers, these data support a possible role for GPR15 in the ethnically dependent
differential prevalence of HIV.
PMID- 26441694
TI - Regulatory Issues Surrounding Audit of Electronic Cigarette Charge Composition.
PMID- 26441695
TI - Neurobiology of Sleep Disturbances in PTSD Patients and Traumatized Controls: MRI
and SPECT Findings.
AB - OBJECTIVE: Sleep disturbances such as insomnia and nightmares are core components
of post-traumatic stress disorder (PTSD), yet their neurobiological relationship
is still largely unknown. We investigated brain alterations related to sleep
disturbances in PTSD patients and controls by using both structural and
functional neuroimaging techniques. METHOD: Thirty-nine subjects either
developing (n = 21) or not developing (n = 18) PTSD underwent magnetic resonance
imaging and a symptom-provocation protocol followed by the injection of 99mTc
hexamethylpropyleneamineoxime. Subjects were also tested with diagnostic and self
rating scales on the basis of which a Sleep Disturbances Score (SDS; i.e., amount
of insomnia/nightmares) was computed. RESULTS: Correlations between SDS and gray
matter volume (GMV)/regional cerebral blood flow (rCBF) were computed in the
whole sample and separately in the PTSD and control groups. In the whole sample,
higher sleep disturbances were associated with significantly reduced GMV in
amygdala, hippocampus, anterior cingulate, and insula; increased rCBF in
midbrain, precuneus, and insula; and decreased rCBF in anterior cingulate. This
pattern was substantially confirmed in the PTSD group, but not in controls.
CONCLUSION: Sleep disturbances are associated with GMV loss in anterior
limbic/paralimbic, PTSD-sensitive structures and with functional alterations in
regions implicated in rapid eye movement-sleep control, supporting the existence
of a link between PTSD and sleep disturbance.
PMID- 26441696
TI - Psychosocial adjustment to ALS: a longitudinal study.
AB - For the current study the Lazarian stress-coping theory and the appendant model
of psychosocial adjustment to chronic illness and disabilities (Pakenham, 1999)
has shaped the foundation for identifying determinants of adjustment to ALS. We
aimed to investigate the evolution of psychosocial adjustment to ALS and to
determine its long-term predictors. A longitudinal study design with four
measurement time points was therefore, used to assess patients' quality of life,
depression, and stress-coping model related aspects, such as illness
characteristics, social support, cognitive appraisals, and coping strategies
during a period of 2 years. Regression analyses revealed that 55% of the variance
of severity of depressive symptoms and 47% of the variance in quality of life at
T2 was accounted for by all the T1 predictor variables taken together. On the
level of individual contributions, protective buffering, and appraisal of own
coping potential accounted for a significant percentage in the variance in
severity of depressive symptoms, whereas problem management coping strategies
explained variance in quality of life scores. Illness characteristics at T2 did
not explain any variance of both adjustment outcomes. Overall, the pattern of the
longitudinal results indicated stable depressive symptoms and quality of life
indices reflecting a successful adjustment to the disease across four measurement
time points during a period of about two years. Empirical evidence is provided
for the predictive value of social support, cognitive appraisals, and coping
strategies, but not illness parameters such as severity and duration for
adaptation to ALS. The current study contributes to a better conceptualization of
adjustment, allowing us to provide evidence-based support beyond medical and
physical intervention for people with ALS.
PMID- 26441697
TI - Thematic orders and the comprehension of subject-extracted relative clauses in
Mandarin Chinese.
AB - This study investigates the comprehension of three kinds of subject-extracted
relative clauses (SRs) in Mandarin Chinese: standard SRs, relative clauses
involving the disposal ba construction ("disposal SRs"), and relative clauses
involving the long passive bei constructions ("passive SRs"). In a self-paced
reading experiment, the regions before the relativizer (where the sentential
fragments are temporarily ambiguous) showed reading patterns consistent with
expectation-based incremental processing: standard SRs, with the highest
constructional frequency and the least complex syntactic structure, were
processed faster than the other two variants. However, in the regions after the
relativizer and the head noun where the existence of a relative clause is
unambiguously indicated, a top-down global effect of thematic ordering was
observed: passive SRs, whose thematic role order conforms to the canonical
thematic order of Chinese, were read faster than both the standard SRs and the
disposal SRs. Taken together, these results suggest that two expectation-based
processing factors are involved in the comprehension of Chinese relative clauses,
including both the structural probabilities of pre-relativizer constituents and
the overall surface thematic orders in the relative clauses.
PMID- 26441698
TI - Hallucinations as a trauma-based memory: implications for psychological
interventions.
AB - The relationship between hallucinations and life events is a topic of significant
clinical importance. This review discusses the extent to which auditory and
visual hallucinations may be directly related to traumatic events. Evidence
suggests that intrusive images occur frequently within individuals who also
report hallucinatory experiences. However, there has been limited research
specifically investigating the extent to which hallucinations are the re
experiencing of a traumatic event. Our current theoretical understanding of these
relationships, along with methodological difficulties associated with research in
this area, are considered. Recent clinical studies, which adopt interventions
aimed at the symptoms of posttraumatic stress disorder in people diagnosed with a
psychotic disorder, are reviewed. There is a need for the development of evidence
based interventions in this area.
PMID- 26441699
TI - Mental health literacy: a cross-cultural approach to knowledge and beliefs about
depression, schizophrenia and generalized anxiety disorder.
AB - Many families worldwide have at least one member with a behavioral or mental
disorder, and yet the majority of the public fails to correctly recognize
symptoms of mental illness. Previous research has found that Mental Health
Literacy (MHL)-the knowledge and positive beliefs about mental disorders-tends to
be higher in European and North American cultures, compared to Asian and African
cultures. Nonetheless quantitative research examining the variables that explain
this cultural difference remains limited. The purpose of our study was fourfold:
(a) to validate measures of MHL cross-culturally, (b) to examine the MHL model
quantitatively, (c) to investigate cultural differences in the MHL model, and (d)
to examine collectivism as a predictor of MHL. We validated measures of MHL in
European American and Indian samples. The results lend strong quantitative
support to the MHL model. Recognition of symptoms of mental illness was a central
variable: greater recognition predicted greater endorsement of social causes of
mental illness and endorsement of professional help-seeking as well as lesser
endorsement of lay help-seeking. The MHL model also showed an overwhelming
cultural difference; namely, lay help-seeking beliefs played a central role in
the Indian sample, and a negligible role in the European American sample.
Further, collectivism was positively associated with causal beliefs of mental
illness in the European American sample, and with lay help-seeking beliefs in the
Indian sample. These findings demonstrate the importance of understanding
cultural differences in beliefs about mental illness, particularly in relation to
help-seeking beliefs.
PMID- 26441700
TI - The sense of agency in autism spectrum disorders: a dissociation between
prospective and retrospective mechanisms?
AB - While a large number of studies have reported impairments in social and
interpersonal abilities in individuals with autism spectrum disorder (ASD),
relatively few studies have focused on self-related knowledge in this population.
One of the processes implicated in the physical dimension of the Self is the
sense of agency (SoA), i.e., the experience of initiating and controlling one's
own actions and producing desired changes in the world via these actions. So far,
the few studies investigating SoA in ASD have reported contrasting results, with
some showing spared, others impaired SoA. Here, we review the existing literature
and suggest that the distinction between prospective and retrospective mechanisms
of the SoA might help reconcile the existing findings. In the light of a multi
componential model of SoA, we propose the view that a specific impairment at the
level of prospective mechanisms acting on internal agency signals (i.e., the
intention, action selection, or command produced to achieve the goal) may be
responsible for the reduced SoA in ASD, along with spared retrospective
mechanisms. Future research should shed light on the impact of abnormal SoA on
social and self-related dysfunctions in ASD.
PMID- 26441702
TI - Prior knowledge in recalling arguments in bioethical dilemmas.
AB - Prior knowledge is known to facilitate learning new information. Normally in
studies confirming this outcome the relationship between prior knowledge and the
topic to be learned is obvious: the information to be acquired is part of the
domain or topic to which the prior knowledge belongs. This raises the question as
to whether prior knowledge of various domains facilitates recalling information.
In this study 79 eleventh-grade students completed a questionnaire on their prior
knowledge of seven different domains related to the bioethical dilemma of
prenatal diagnostics. The students read a text containing arguments for and
arguments against prenatal diagnostics. After 1 week and again 12 weeks later
they were asked to write down all the arguments they remembered. Prior knowledge
helped them recall the arguments 1 week (r = 0.350) and 12 weeks (r = 0.316)
later. Prior knowledge of three of the seven domains significantly helped them
recall the arguments 1 week later (correlations between r = 0.194 and 0.394).
Partial correlations with interest as a control item revealed that interest did
not explain the relationship between prior knowledge and recall. Prior knowledge
of different domains jointly supports the recall of arguments related to
bioethical topics.
PMID- 26441701
TI - Top-down modulation of visual processing and knowledge after 250 ms supports
object constancy of category decisions.
AB - People categorize objects more slowly when visual input is highly impoverished
instead of optimal. While bottom-up models may explain a decision with optimal
input, perceptual hypothesis testing (PHT) theories implicate top-down processes
with impoverished input. Brain mechanisms and the time course of PHT are largely
unknown. This event-related potential study used a neuroimaging paradigm that
implicated prefrontal cortex in top-down modulation of occipitotemporal cortex.
Subjects categorized more impoverished and less impoverished real and pseudo
objects. PHT theories predict larger impoverishment effects for real than pseudo
objects because top-down processes modulate knowledge only for real objects, but
different PHT variants predict different timing. Consistent with parietal
prefrontal PHT variants, around 250 ms, the earliest impoverished real object
interaction started on an N3 complex, which reflects interactive cortical
activity for object cognition. N3 impoverishment effects localized to both
prefrontal and occipitotemporal cortex for real objects only. The N3 also showed
knowledge effects by 230 ms that localized to occipitotemporal cortex. Later
effects reflected (a) word meaning in temporal cortex during the N400, (b)
internal evaluation of prior decision and memory processes and secondary higher
order memory involving anterotemporal parts of a default mode network during
posterior positivity (P600), and (c) response related activity in posterior
cingulate during an anterior slow wave (SW) after 700 ms. Finally, response
activity in supplementary motor area during a posterior SW after 900 ms showed
impoverishment effects that correlated with RTs. Convergent evidence from studies
of vision, memory, and mental imagery which reflects purely top-down inputs,
indicates that the N3 reflects the critical top-down processes of PHT. A hybrid
multiple-state interactive, PHT and decision theory best explains the visual
constancy of object cognition.
PMID- 26441704
TI - Children's and adolescents' snacking: interplay between the individual and the
school class.
AB - OBJECTIVE: In schools, perceived norms of classmates facilitate but can also
inhibit unhealthy food intake in children and adolescents. However, the role of
actual class behaviors and attitudes is less established. Thus, the present study
examined classmates' actual eating behavior and food preferences in relation to
actual food intake. In addition, it tested whether these normative effects are
facilitated by corresponding individual and class food preferences or a positive
social self-concept. METHODS: The food preferences, social self-concept, and
unhealthy snacking frequency of 734 Finnish, 829 German, and 555 Romanian
children and adolescents (aged 8-19) from 127 school-classes were assessed.
RESULTS: Multilevel analysis at individual and class level showed that classmates
shared similar snacking habits (14.7% variance). Moreover, the unhealthy food
preference of a school-class was associated with its collective snacking
[[Formula: see text], p < 0.001, PRV = 0.32). This effect was facilitated by
individual, unhealthy food preferences [[Formula: see text], p < 0.001, PRV =
0.57] and a positive social self-concept [[Formula: see text], p = 0.015, PRV =
0.12]. CONCLUSIONS: Actual class norms are related to children's and adolescents'
eating, but their impact depends on individual differences in preferences and
social self-concept.
PMID- 26441703
TI - The neuroscience of positive memory deficits in depression.
AB - Adults with unipolar depression typically show poor episodic memory for positive
material, but the neuroscientific mechanisms responsible for this deficit have
not been characterized. I suggest a simple hypothesis: weak memory for positive
material in depression reflects disrupted communication between the mesolimbic
dopamine pathway and medial temporal lobe (MTL) memory systems during encoding.
This proposal draws on basic research showing that dopamine release in the
hippocampus is critical for the transition from early- to late-phase long-term
potentiation (LTP) that marks the conversion of labile, short-term memories into
stable, long-term memories. Neuroimaging and pharmacological data from healthy
humans paint a similar picture: activation of the mesolimbic reward circuit
enhances encoding and boosts retention. Unipolar depression is characterized by
anhedonia-loss of pleasure-and reward circuit dysfunction, which is believed to
reflect negative effects of stress on the mesolimbic dopamine pathway. Thus, I
propose that the MTL is deprived of strengthening reward signals in depressed
adults and memory for positive events suffers accordingly. Although other
mechanisms are important, this hypothesis holds promise as an explanation for
positive memory deficits in depression.
PMID- 26441705
TI - The impact of threat of shock on the framing effect and temporal discounting:
executive functions unperturbed by acute stress?
AB - Anxiety and stress-related disorders constitute a large global health burden, but
are still poorly understood. Prior work has demonstrated clear impacts of stress
upon basic cognitive function: biasing attention toward unexpected and
potentially threatening information and instantiating a negative affective bias.
However, the impact that these changes have on higher-order, executive, decision
making processes is unclear. In this study, we examined the impact of a
translational within-subjects stress induction (threat of unpredictable shock) on
two well-established executive decision-making biases: the framing effect (N =
83), and temporal discounting (N = 36). In both studies, we demonstrate (a) clear
subjective effects of stress, and (b) clear executive decision-making biases but
(c) no impact of stress on these decision-making biases. Indeed, Bayes factor
analyses confirmed substantial preference for decision-making models that did not
include stress. We posit that while stress may induce subjective mood change and
alter low-level perceptual and action processes (Robinson et al., 2013c), some
higher-level executive processes remain unperturbed by these impacts. As such,
although stress can induce a transient affective biases and altered mood, these
need not result in poor financial decision-making.
PMID- 26441706
TI - Dubious decision evidence and criterion flexibility in recognition memory.
AB - When old-new recognition judgments must be based on ambiguous memory evidence, a
proper criterion for responding "old" can substantially improve accuracy, but
participants are typically suboptimal in their placement of decision criteria.
Various accounts of suboptimal criterion placement have been proposed. The most
parsimonious, however, is that subjects simply over-rely on memory evidence -
however faulty - as a basis for decisions. We tested this account with a novel
recognition paradigm in which old-new discrimination was minimal and critical
errors were avoided by adopting highly liberal or conservative biases. In
Experiment 1, criterion shifts were necessary to adapt to changing target
probabilities or, in a "security patrol" scenario, to avoid either letting
dangerous people go free (misses) or harming innocent people (false alarms).
Experiment 2 added a condition in which financial incentives drove criterion
shifts. Critical errors were frequent, similar across sources of motivation, and
only moderately reduced by feedback. In Experiment 3, critical errors were only
modestly reduced in a version of the security patrol with no study phase. These
findings indicate that participants use even transparently non-probative
information as an alternative to heavy reliance on a decision rule, a strategy
that precludes optimal criterion placement.
PMID- 26441707
TI - Self-concept in fairness and rule establishment during a competitive game: a
computational approach.
AB - People consider fairness as well as their own interest when making decisions in
economic games. The present study proposes a model that encompasses the self
concept determined by one's own kindness as a factor of fairness. To observe
behavioral patterns that reflect self-concept and fairness, a chicken game
experiment was conducted. Behavioral data demonstrates four distinct patterns;
"switching," "mutual rush," "mutual avoidance," and "unfair" patterns. Model
estimation of chicken game data shows that a model with self-concept predicts
those behaviors better than previous models of fairness, suggesting that self
concept indeed affects human behavior in competitive economic games. Moreover, a
non-stationary parameter analysis revealed the process of reaching consensus
between the players in a game. When the models were fitted to a continuous time
window, the parameters of the players in a pair with "switching" and "mutual
avoidance" patterns became similar as the game proceeded, suggesting that the
players gradually formed a shared rule during the game. In contrast, the
difference of parameters between the players in the "unfair" and "mutual rush"
patterns did not become stable. The outcomes of the present study showed that
people are likely to change their strategy until they reach a mutually beneficial
status.
PMID- 26441708
TI - Hypothesis-driven research for G * E interactions: the relationship between
oxytocin, parental divorce during adolescence, and depression in young adulthood.
AB - Research in molecular genetics has generally focused on genome-wide association
studies (GWAS) and exploratory candidate gene and candidate gene-environment (G *
E) studies. In this article it is proposed that hypothesis-driven and
biologically informed research provides a complementary approach to GWAS to
advance pressing research questions about G * E relations that are of public
health relevance. Prior research studies and developmental and evolutionary
theory were used to guide hypothesis testing of G * E relationships in this
study. The study investigated whether the oxytocin polymorphism, rs53576,
moderated the relationship between parental divorce during adolescence and
depression symptoms in young adulthood. Oxytocin is a neuropeptide that has been
related to the regulation of complex social cognition and behaviors such as
empathy, attachment, and nurturance. We hypothesized that the GG polymorphism
would be associated with more depressive symptoms following parental divorce, and
that this effect would be stronger in females than males. The sample consisted of
340 individuals who participated in a longitudinal study with data used both from
adolescence and young adulthood. Findings using prospective follow-up and
autoregressive change models supported the hypothesized relationships. Young
adult females who had experienced parental divorce during adolescence and had the
GG oxytocin genotype reported almost twice as many depressive symptoms relative
to young adult females who also experienced parental divorce during adolescence
but had the AA or AG genotype. This pattern was not indicated among males.
Findings were discussed with regard to how molecular genetic factors in
combination with environmental stressors, such parental divorce, framed within a
developmental framework may facilitate the future study of G * E relationships in
the parental divorce-child adjustment literature and contribute to a prevention
science perspective.
PMID- 26441710
TI - Suspending the next turn as a form of repair initiation: evidence from Argentine
Sign Language.
AB - Practices of other-initiated repair deal with problems of hearing or
understanding what another person has said in the fast-moving turn-by-turn flow
of conversation. As such, other-initiated repair plays a fundamental role in the
maintenance of intersubjectivity in social interaction. This study finds and
analyses a special type of other-initiated repair that is used in turn-by-turn
conversation in a sign language: Argentine Sign Language (Lengua de Senas
Argentina or LSA). We describe a type of response termed a "freeze-look," which
occurs when a person has just been asked a direct question: instead of answering
the question in the next turn position, the person holds still while looking
directly at the questioner. In these cases it is clear that the person is aware
of having just been addressed and is not otherwise accounting for their delay in
responding (e.g., by displaying a "thinking" face or hesitation, etc.). We find
that this behavior functions as a way for an addressee to initiate repair by the
person who asked the question. The "freeze-look" results in the questioner "re
doing" their action of asking a question, for example by repeating or rephrasing
it. Thus, we argue that the "freeze-look" is a practice for other-initiation of
repair. In addition, we argue that it is an "off-record" practice, thus
contrasting with known on-record practices such as saying "Huh?" or equivalents.
The findings aim to contribute to research on human understanding in everyday
turn-by-turn conversation by looking at an understudied sign language, with
possible implications for our understanding of visual bodily communication in
spoken languages as well.
PMID- 26441709
TI - Motivation for aggressive religious radicalization: goal regulation theory and a
personality * threat * affordance hypothesis.
AB - A new set of hypotheses is presented regarding the cause of aggressive religious
radicalization (ARR). It is grounded in classic and contemporary theory of human
motivation and goal regulation, together with recent empirical advances in
personality, social, and neurophysiological psychology. We specify personality
traits, threats, and group affordances that combine to divert normal motivational
processes toward ARR. Conducive personality traits are oppositional, anxiety
prone, and identity-weak (i.e., morally bewildered). Conducive threats are those
that arise from seemingly insurmountable external forces and frustrate effective
goal regulation. Conducive affordances include opportunity for immediate and
concrete engagement in active groups that are powered by conspiracy narratives,
infused with cosmic significance, encouraging of moral violence, and sealed with
religious unfalsifiability. We propose that ARR is rewarding because it can spur
approach motivated states that mask vulnerability for people whose dispositions
and circumstances would otherwise leave them mired in anxious distress.
PMID- 26441711
TI - Doctor, what does my positive test mean? From Bayesian textbook tasks to
personalized risk communication.
AB - Most of the research on Bayesian reasoning aims to answer theoretical questions
about the extent to which people are able to update their beliefs according to
Bayes' Theorem, about the evolutionary nature of Bayesian inference, or about the
role of cognitive abilities in Bayesian inference. Few studies aim to answer
practical, mainly health-related questions, such as, "What does it mean to have a
positive test in a context of cancer screening?" or "What is the best way to
communicate a medical test result so a patient will understand it?". This type of
research aims to translate empirical findings into effective ways of providing
risk information. In addition, the applied research often adopts the paradigms
and methods of the theoretically-motivated research. But sometimes it works the
other way around, and the theoretical research borrows the importance of the
practical question in the medical context. The study of Bayesian reasoning is
relevant to risk communication in that, to be as useful as possible, applied
research should employ specifically tailored methods and contexts specific to the
recipients of the risk information. In this paper, we concentrate on the
communication of the result of medical tests and outline the epidemiological and
test parameters that affect the predictive power of a test-whether it is correct
or not. Building on this, we draw up recommendations for better practice to
convey the results of medical tests that could inform health policy makers (What
are the drawbacks of mass screenings?), be used by health practitioners and, in
turn, help patients to make better and more informed decisions.
PMID- 26441712
TI - Framing effects reveal discrete lexical-semantic and sublexical procedures in
reading: an fMRI study.
AB - According to the dual-route model, a printed string of letters can be processed
by either a grapheme-to-phoneme conversion (GPC) route or a lexical-semantic
route. Although meta-analyses of the imaging literature support the existence of
distinct but interacting reading procedures, individual neuroimaging studies that
explored neural correlates of reading yielded inconclusive results. We used a
list-manipulation paradigm to provide a fresh empirical look at this issue and to
isolate specific areas that underlie the two reading procedures. In a lexical
condition, we embedded disyllabic Italian words (target stimuli) in lists of
either loanwords or trisyllabic Italian words with unpredictable stress position.
In a GPC condition, similar target stimuli were included within lists of
pseudowords. The procedure was designed to induce participants to emphasize
either the lexical-semantic or the GPC reading procedure, while controlling for
possible linguistic confounds and keeping the reading task requirements stable
across the two conditions. Thirty-three adults participated in the behavioral
study, and 20 further adult participants were included in the fMRI study. At the
behavioral level, we found sizeable effects of the framing manipulations that
included slower voice onset times for stimuli in the pseudoword frames. At the
functional anatomical level, the occipital and temporal regions, and the
intraparietal sulcus were specifically activated when subjects were reading
target words in a lexical frame. The inferior parietal and anterior fusiform
cortex were specifically activated in the GPC condition. These patterns of
activation represented a valid classifying model of fMRI images associated with
target reading in both frames in the multi-voxel pattern analyses. Further
activations were shared by the two procedures in the occipital and inferior
parietal areas, in the premotor cortex, in the frontal regions and the left
supplementary motor area. These regions are most likely involved in either early
input or late output processes.
PMID- 26441713
TI - Improving working memory abilities in individuals with Down syndrome: a treatment
case study.
AB - Working memory (WM) skills of individuals with Down's syndrome (DS) tend to be
very poor compared to typically developing children of similar mental age. In
particular, research has found that in individuals with DS visuo-spatial WM is
better preserved than verbal WM. This study investigated whether it is possible
to train short-term memory (STM) and WM abilities in individuals with DS. The
cases of two teenage children are reported: EH, 17 years and 3 months, and AS, 15
years and 11 months. A school-based treatment targeting visuo-spatial WM was
given to EH and AS for six weeks. Both prior to and after the treatment, they
completed a set of assessments to measure WM abilities and their performance was
compared with younger typically developing non-verbal mental age controls. The
results showed that the trained participants improved their performance in some
of the trained and non-trained WM tasks proposed, especially with regard to the
tasks assessing visuo-spatial WM abilities. These findings are discussed on the
basis of their theoretical, educational, and clinical implications.
PMID- 26441714
TI - Multimethod latent class analysis.
AB - Correct and, hence, valid classifications of individuals are of high importance
in the social sciences as these classifications are the basis for diagnoses
and/or the assignment to a treatment. The via regia to inspect the validity of
psychological ratings is the multitrait-multimethod (MTMM) approach. First, a
latent variable model for the analysis of rater agreement (latent rater agreement
model) will be presented that allows for the analysis of convergent validity
between different measurement approaches (e.g., raters). Models of rater
agreement are transferred to the level of latent variables. Second, the latent
rater agreement model will be extended to a more informative MTMM latent class
model. This model allows for estimating (i) the convergence of ratings, (ii)
method biases in terms of differential latent distributions of raters and
differential associations of categorizations within raters (specific rater bias),
and (iii) the distinguishability of categories indicating if categories are
satisfyingly distinct from each other. Finally, an empirical application is
presented to exemplify the interpretation of the MTMM latent class model.
PMID- 26441715
TI - Erotic subset for the Nencki Affective Picture System (NAPS ERO): cross-sexual
comparison study.
AB - Research on the processing of sexual stimuli has proved that such material has
high priority in human cognition. Yet, although sex differences in response to
sexual stimuli were extensively discussed in the literature, sexual orientation
was given relatively little consideration, and material suitable for relevant
research is difficult to come by. With this in mind, we present a collection of
200 erotic images, accompanied by their self-report ratings of emotional valence
and arousal by homo- and heterosexual males and females (n = 80, divided into
four equal-sized subsamples). The collection complements the Nencki Affective
Picture System (NAPS) and is intended to be used as stimulus material in
experimental research. The erotic images are divided into five categories,
depending on their content: opposite-sex couple (50), male couple (50), female
couple (50), male (25) and female (25). Additional 100 control images from the
NAPS depicting people in a non-erotic context were also used in the study. We
showed that recipient sex and sexual orientation strongly influenced the
evaluation of erotic content. Thus, comparisons of valence and arousal ratings in
different subject groups will help researchers select stimuli set for the purpose
of various experimental designs. To facilitate the use of the dataset, we provide
an on-line tool, which allows the user to browse the images interactively and
select proper stimuli on the basis of several parameters. The NAPS ERO image
collection together with the data are available to the scientific community for
non-commercial use at http://naps.nencki.gov.pl.
PMID- 26441717
TI - A functional approach to movement analysis and error identification in sports and
physical education.
AB - In a hypothesis-and-theory paper, a functional approach to movement analysis in
sports is introduced. In this approach, contrary to classical concepts, it is not
anymore the "ideal" movement of elite athletes that is taken as a template for
the movements produced by learners. Instead, movements are understood as the
means to solve given tasks that in turn, are defined by to-be-achieved task
goals. A functional analysis comprises the steps of (1) recognizing constraints
that define the functional structure, (2) identifying sub-actions that subserve
the achievement of structure-dependent goals, (3) explicating modalities as
specifics of the movement execution, and (4) assigning functions to actions, sub
actions and modalities. Regarding motor-control theory, a functional approach can
be linked to a dynamical-system framework of behavioral shaping, to cognitive
models of modular effect-related motor control as well as to explicit concepts of
goal setting and goal achievement. Finally, it is shown that a functional
approach is of particular help for sports practice in the context of structuring
part practice, recognizing functionally equivalent task solutions, finding
innovative technique alternatives, distinguishing errors from style, and
identifying root causes of movement errors.
PMID- 26441716
TI - Subjective memory complaints among patients on sick leave are associated with
symptoms of fatigue and anxiety.
AB - OBJECTIVE: The aim of this study was to identify symptoms associated with
subjective memory complaints (SMCs) among subjects who are currently on sick
leave due to symptoms of chronic pain, fatigue, depression, anxiety, and
insomnia. METHODS: This was a cross-sectional study, subjects (n = 167) who were
currently on sick leave were asked to complete an extensive survey consisting of
the following: items addressing their sociodemographics, one item from the SF-8
health survey measuring pain, Chalder Fatigue Questionnaire, Hospital Anxiety and
Depression Scale, Insomnia Severity Index, and Everyday Memory Questionnaire -
Revised. General linear modeling was used to analyze variables associated with
SMCs. RESULTS: Symptoms of fatigue (p-value < 0.001) and anxiety (p-value =
0.001) were uniquely and significantly associated with perceived memory failures.
The associations with symptoms of pain, depression, and insomnia were not
statistically significant. CONCLUSIONS: Subjective memory complaints should be
recognized as part of the complex symptomatology among patients who report
multiple symptoms, especially in cases of fatigue and anxiety. Self-report
questionnaires measuring perceived memory failures may be a quick and easy way to
incorporate and extend this knowledge into clinical practice.
PMID- 26441718
TI - Sound frequency affects speech emotion perception: results from congenital
amusia.
AB - Congenital amusics, or "tone-deaf" individuals, show difficulty in perceiving and
producing small pitch differences. While amusia has marked effects on music
perception, its impact on speech perception is less clear. Here we test the
hypothesis that individual differences in pitch perception affect judgment of
emotion in speech, by applying low-pass filters to spoken statements of emotional
speech. A norming study was first conducted on Mechanical Turk to ensure that the
intended emotions from the Macquarie Battery for Evaluation of Prosody were
reliably identifiable by US English speakers. The most reliably identified
emotional speech samples were used in Experiment 1, in which subjects performed a
psychophysical pitch discrimination task, and an emotion identification task
under low-pass and unfiltered speech conditions. Results showed a significant
correlation between pitch-discrimination threshold and emotion identification
accuracy for low-pass filtered speech, with amusics (defined here as those with a
pitch discrimination threshold >16 Hz) performing worse than controls. This
relationship with pitch discrimination was not seen in unfiltered speech
conditions. Given the dissociation between low-pass filtered and unfiltered
speech conditions, we inferred that amusics may be compensating for poorer pitch
perception by using speech cues that are filtered out in this manipulation. To
assess this potential compensation, Experiment 2 was conducted using high-pass
filtered speech samples intended to isolate non-pitch cues. No significant
correlation was found between pitch discrimination and emotion identification
accuracy for high-pass filtered speech. Results from these experiments suggest an
influence of low frequency information in identifying emotional content of
speech.
PMID- 26441719
TI - Observed effects of "distributional learning" may not relate to the number of
peaks. A test of "dispersion" as a confounding factor.
AB - Distributional learning of speech sounds is learning from simply being exposed to
frequency distributions of speech sounds in one's surroundings. In laboratory
settings, the mechanism has been reported to be discernible already after a few
minutes of exposure, in both infants and adults. These "effects of distributional
training" have traditionally been attributed to the difference in the number of
peaks between the experimental distribution (two peaks) and the control
distribution (one or zero peaks). However, none of the earlier studies fully
excluded a possibly confounding effect of the dispersion in the distributions.
Additionally, some studies with a non-speech control condition did not control
for a possible difference between processing speech and non-speech. The current
study presents an experiment that corrects both imperfections. Spanish listeners
were exposed to either a bimodal distribution encompassing the Dutch contrast
/alpha/~/a/ or a unimodal distribution with the same dispersion. Before and after
training, their accuracy of categorization of [alpha]- and [a]-tokens was
measured. A traditionally calculated p-value showed no significant difference in
categorization improvement between bimodally and unimodally trained participants.
Because of this null result, a Bayesian method was used to assess the odds in
favor of the null hypothesis. Four different Bayes factors, each calculated on a
different belief in the truth value of previously found effect sizes, indicated
the absence of a difference between bimodally and unimodally trained
participants. The implication is that "effects of distributional training"
observed in the lab are not induced by the number of peaks in the distributions.
PMID- 26441720
TI - A normative inference approach for optimal sample sizes in decisions from
experience.
AB - "Decisions from experience" (DFE) refers to a body of work that emerged in
research on behavioral decision making over the last decade. One of the major
experimental paradigms employed to study experience-based choice is the "sampling
paradigm," which serves as a model of decision making under limited knowledge
about the statistical structure of the world. In this paradigm respondents are
presented with two payoff distributions, which, in contrast to standard
approaches in behavioral economics, are specified not in terms of explicit
outcome-probability information, but by the opportunity to sample outcomes from
each distribution without economic consequences. Participants are encouraged to
explore the distributions until they feel confident enough to decide from which
they would prefer to draw from in a final trial involving real monetary payoffs.
One commonly employed measure to characterize the behavior of participants in the
sampling paradigm is the sample size, that is, the number of outcome draws which
participants choose to obtain from each distribution prior to terminating
sampling. A natural question that arises in this context concerns the "optimal"
sample size, which could be used as a normative benchmark to evaluate human
sampling behavior in DFE. In this theoretical study, we relate the DFE sampling
paradigm to the classical statistical decision theoretic literature and, under a
probabilistic inference assumption, evaluate optimal sample sizes for DFE. In our
treatment we go beyond analytically established results by showing how the
classical statistical decision theoretic framework can be used to derive optimal
sample sizes under arbitrary, but numerically evaluable, constraints. Finally, we
critically evaluate the value of deriving optimal sample sizes under this
framework as testable predictions for the experimental study of sampling behavior
in DFE.
PMID- 26441721
TI - The cognitive-behavioral system of leadership: cognitive antecedents of active
and passive leadership behaviors.
AB - In the present paper, we propose a cognitive-behavioral understanding of active
and passive leadership. Building on core evaluations theory, we offer a model
that explains the emergence of leaders' active and passive behaviors, thereby
predicting stable, inter-individual, as well as variable, intra-individual
differences in both types of leadership behavior. We explain leaders' stable
behavioral tendencies by their fundamental beliefs about themselves, others, and
the world (core evaluations), while their variable, momentary behaviors are
explained by the leaders' momentary appraisals of themselves, others, and the
world (specific evaluations). By introducing interactions between the situation
the leader enters, the leader's beliefs, appraisals, and behavior, we propose a
comprehensive system of cognitive mechanisms that underlie active and passive
leadership behavior.
PMID- 26441722
TI - Moral dilemmas in females: children are more utilitarian than adults.
AB - Influential theories on moral judgments propose that they rely either on emotions
or on innate moral principles. In contrast, the mental model theory postulates
that moral judgments rely on reasoning, either intuition or deliberation. The
theory allows for the possibility that intuitions lead to utilitarian judgments.
This paper reports two experiments involving fifth-grade children, adolescents,
and adults; the results revealed that children reason intuitively to resolve
moral dilemmas in which action and inaction lead to different outcomes. In
particular, the results showed female children to be more utilitarian than female
adults in resolving classical moral dilemmas: they preferred an action that
achieved a good outcome for a greater number of people. Within the mental model
theory's framework there is no reason to expect that females and males differ in
their ability to reason, but at the moment the results for females cannot be
generalized to males who were not properly represented in the adults groups of
the two experiments. The result revealing that (female) children are more
utilitarian than (female) adults, which is hard to explain via many current
theories, was predicted by the mental model theory.
PMID- 26441723
TI - Interference in the processing of adjunct control.
AB - Recent research on the memory operations used in language comprehension has
revealed a selective profile of interference effects during memory retrieval.
Dependencies such as subject-verb agreement show strong facilitatory interference
effects from structurally inappropriate but feature-matching distractors, leading
to illusions of grammaticality (Pearlmutter et al., 1999; Wagers et al., 2009;
Dillon et al., 2013). In contrast, dependencies involving reflexive anaphors are
generally immune to interference effects (Sturt, 2003; Xiang et al., 2009; Dillon
et al., 2013). This contrast has led to the proposal that all anaphors that are
subject to structural constraints are immune to facilitatory interference. Here
we use an animacy manipulation to examine whether adjunct control dependencies,
which involve an interpreted anaphoric relation between a null subject and its
licensor, are also immune to facilitatory interference effects. Our results show
reliable facilitatory interference in the processing of adjunct control
dependencies, which challenges the generalization that anaphoric dependencies as
a class are immune to such effects. To account for the contrast between adjunct
control and reflexive dependencies, we suggest that variability within anaphora
could reflect either an inherent primacy of animacy cues in retrieval processes,
or differential degrees of match between potential licensors and the retrieval
probe.
PMID- 26441724
TI - Phonological similarity affects production of gestures, even in the absence of
overt speech.
AB - Highlights Does phonological similarity affect gesture production in the absence
of speech?Participants produced gestures from pictures with no words presented or
spoken.Same pictures and gestures but different training labels were
used.Phonologically similar labels led to more errors in subsequent
gestures.Thus, phonological similarity affects gesture production in the absence
of speech. Are manual gestures affected by inner speech? This study tested the
hypothesis that phonological form influences gesture by investigating whether
phonological similarity between words that describe motion gestures creates
interference for production of those gestures in the absence of overt speech.
Participants learned to respond to a picture of a bottle by gesturing to open the
bottle's cap, and to a picture of long hair by gesturing to twirl the hair. In
one condition, the gestures were introduced with phonologically-similar labels
"twist" and "twirl" (similar condition), while in the other condition, they were
introduced with phonologically-dissimilar labels "unscrew" and "twirl"
(dissimilar condition). During the actual experiment, labels were not produced
and participants only gestured by looking at pictures. In both conditions,
participants also gestured to a control pair that was used as a baseline.
Participants made significantly more errors on gestures in the similar than
dissimilar condition after correction for baseline differences. This finding
shows the influence of phonology on gesture production in the absence of overt
speech and poses new constraints on the locus of the interaction between language
and gesture systems.
PMID- 26441725
TI - The acquisition process of musical tonal schema: implications from connectionist
modeling.
AB - Using connectionist modeling, we address fundamental questions concerning the
acquisition process of musical tonal schema of listeners. Compared to models of
previous studies, our connectionist model (Learning Network for Tonal Schema,
LeNTS) was better equipped to fulfill three basic requirements. Specifically,
LeNTS was equipped with a learning mechanism, bound by culture-general
properties, and trained by sufficient melody materials. When exposed to Western
music, LeNTS acquired musical 'scale' sensitivity early and 'harmony' sensitivity
later. The order of acquisition of scale and harmony sensitivities shown by LeNTS
was consistent with the culture-specific acquisition order shown by musically
westernized children. The implications of these results for the acquisition
process of a tonal schema of listeners are as follows: (a) the acquisition
process may entail small and incremental changes, rather than large and stage
like changes, in corresponding neural circuits; (b) the speed of schema
acquisition may mainly depend on musical experiences rather than maturation; and
PMID- 26441726
TI - What is the right place for atypical exemplars? Commentary: The right hemisphere
contribution to semantic categorization: a TMS study.
PMID- 26441727
TI - The effect of gaze-contingent stimulus elimination on preference judgments.
AB - This study examined how stimulus elimination (SE) in a preference judgment task
affects observers' choices. Previous research suggests that biasing gaze toward
one alternative can increase preference for it; this preference reciprocally
promotes gaze bias. Shimojo et al. (2003) called this phenomenon the Gaze Cascade
Effect. They showed that the likelihood that an observer's gaze was directed
toward their chosen alternative increased steadily until the moment of choosing.
Therefore, we tested whether observers would prefer an alternative at which they
had been gazing last if both alternatives were removed prior to the start of this
rising gaze likelihood. To test this, we used a preference judgment task and
controlled stimulus presentation based on gaze using an eye-tracking system. A
pair of non-sensical figures was presented on the computer screen and both
stimuli were eliminated while participants were still making their preference
decision. The timing of the elimination differed between two experiments. In
Experiment 1, after gazing at both stimuli one or more times, stimuli were
removed when the participant's gaze fell on one alternative, pre-selected as the
target stimulus. There was no significant difference in the preference of the two
alternatives. In Experiment 2, we did not predefine any target stimulus. After
the participant gazed at both stimuli one or more times, both stimuli were
eliminated when the participant next fixated on either. The likelihood of
choosing the stimulus that was gazed at last (at the moment of elimination) was
greater than chance. Results showed that controlling participants' choices using
gaze-contingent SE was impossible, but the different results between these two
experiments suggest that participants decided which stimulus to choose during
their first period of gazing at each alternative. Thus, we could predict
participants' choices by analyzing eye movement patterns at the moment of SE.
PMID- 26441728
TI - Tolerating the "doubting Thomas": how centrality of religious beliefs vs.
practices influences prejudice against atheists.
AB - Past research has found a robust effect of prejudice against atheists in largely
Christian-dominated (belief-oriented) samples. We propose that religious
centrality of beliefs vs. practices influences attitudes toward atheists, such
that religious groups emphasizing beliefs perceive non-believers more negatively
than believers, while groups emphasizing practices perceive non-practicing
individuals more negatively than practicing individuals. Studies 1-2, in surveys
of 41 countries, found that Muslims and Protestants (belief-oriented) had more
negative attitudes toward atheists than did Jews and Hindus (practice-oriented).
Study 3 experimentally manipulated a target individual's beliefs and practices.
Protestants had more negative attitudes toward a non-believer (vs. a believer),
whereas Jews had more negative attitudes toward a non-practicing individual (vs.
a practicing individual, particularly when they had a Jewish background). This
research has implications for the psychology of religion, anti-atheist prejudice,
and cross-cultural attitudes regarding where dissent in beliefs or practices may
be tolerated or censured within religious groups.
PMID- 26441729
TI - Dissociative states in dreams and brain chaos: implications for creative
awareness.
AB - This article reviews recent findings indicating some common brain processes
during dissociative states and dreaming with the aim to outline a perspective
that neural chaotic states during dreaming can be closely related to dissociative
states that may manifest in dreams scenery. These data are in agreement with
various clinical findings that dissociated states can be projected into the
"dream scenery" in REM sleep periods and dreams may represent their specific
interactions that may uncover unusual psychological potential of creativity in
psychotherapy, art, and scientific discoveries.
PMID- 26441730
TI - Labile sleep promotes awareness of abstract knowledge in a serial reaction time
task.
AB - Sleep has been identified as a critical brain state enhancing the probability of
gaining insight into covert task regularities. Both non-rapid eye movement (NREM)
and rapid eye movement (REM) sleep have been implicated with offline re
activation and reorganization of memories supporting explicit knowledge
generation. According to two-stage models of sleep function, offline processing
of information during sleep is sequential requiring multiple cycles of NREM and
REM sleep stages. However, the role of overnight dynamic sleep macrostructure for
insightfulness has not been studied so far. In the present study, we test the
hypothesis that the frequency of interactions between NREM and REM sleep stages
might be critical for awareness after sleep. For that aim, the rate of sleep
stage transitions was evaluated in 53 participants who learned implicitly a
serial reaction time task (SRTT) in which a determined sequence was inserted. The
amount of explicit knowledge about the sequence was established by verbal recall
after a night of sleep following SRTT learning. Polysomnography was recorded in
this night and in a control night before and was analyzed to compare the rate of
sleep-stage transitions between participants who did or did not gain awareness of
task regularity after sleep. Indeed, individual ability of explicit knowledge
generation was strongly associated with increased rate of transitions between
NREM and REM sleep stages and between light sleep stages and slow wave sleep.
However, the rate of NREM-REM transitions specifically predicted the amount of
explicit knowledge after sleep in a trait-dependent way. These results
demonstrate that enhanced lability of sleep goes along with individual ability of
knowledge awareness. Observations suggest that facilitated dynamic interactions
between sleep stages, particularly between NREM and REM sleep stages play a role
for offline processing which promotes rule extraction and awareness.
PMID- 26441732
TI - Cross-linguistic evidence for gender as a prominence feature.
AB - This paper discusses recent findings in the online sentence processing research
that suggest to consider gender information a prominence feature. Prominence
features are hierarchically ordered information types that interact with formal
features of arguments (e.g., grammatical functions, thematic roles) and thus
determine the readers' ability to efficiently interpret linguistic ambiguities.
While previous research addressed a number of prominence features (e.g., animacy,
definiteness, person), there is now first empirical evidence indicating that
gender information also influences the assignment of thematic roles across
languages. Grammatically masculine role nouns are processed faster as agents than
patients compared to feminine ones. Stereotypically male role nouns (e.g.,
electrician) are integrated with an agent role easier than neutral ones (e.g.,
musician), which in turn are integrated easier than female ones (e.g.,
beautician). Conceptualizing gender as a prominence feature will not only expand
our knowledge about information types relevant for online comprehension but also
uncover subtle gender biases present in language. The present work explores the
possibility for a theoretical integration of social psychological and
psycholinguistic research focusing on gender with research on prominence.
Potential advantages an interdisciplinary approach to the study of gender as a
prominence feature, open questions and future directions are discussed.
PMID- 26441731
TI - Brain asymmetry in the white matter making and globularity.
AB - Recent studies from the field of language genetics and evolutionary anthropology
have put forward the hypothesis that the emergence of our species-specific brain
is to be understood not in terms of size, but in light of developmental changes
that gave rise to a more globular braincase configuration after the split from
Neanderthals-Denisovans. On the grounds that (i) white matter myelination is
delayed relative to other brain structures and, in humans, is protracted compared
with other primates and that (ii) neural connectivity is linked genetically to
our brain/skull morphology and language-ready brain, I argue that one significant
evolutionary change in Homo sapiens' lineage is the interhemispheric connectivity
mediated by the Corpus Callosum. The size, myelination and fiber caliber of the
Corpus Callosum present an anterior-to-posterior increase, in a way that inter
hemispheric connectivity is more prominent in the sensory motor areas, whereas
"high- order" areas are more intra-hemispherically connected. Building on
evidence from language-processing studies that account for this asymmetry
('lateralization') in terms of brain rhythms, I present an evo-devo hypothesis
according to which the myelination of the Corpus Callosum, Brain Asymmetry, and
Globularity are conjectured to make up the angles of a co-evolutionary triangle
that gave rise to our language-ready brain.
PMID- 26441733
TI - Encoding audio motion: spatial impairment in early blind individuals.
AB - The consequence of blindness on auditory spatial localization has been an
interesting issue of research in the last decade providing mixed results.
Enhanced auditory spatial skills in individuals with visual impairment have been
reported by multiple studies, while some aspects of spatial hearing seem to be
impaired in the absence of vision. In this study, the ability to encode the
trajectory of a 2-dimensional sound motion, reproducing the complete movement,
and reaching the correct end-point sound position, is evaluated in 12 early blind
(EB) individuals, 8 late blind (LB) individuals, and 20 age-matched sighted
blindfolded controls. EB individuals correctly determine the direction of the
sound motion on the horizontal axis, but show a clear deficit in encoding the
sound motion in the lower side of the plane. On the contrary, LB individuals and
blindfolded controls perform much better with no deficit in the lower side of the
plane. In fact the mean localization error resulted 271 +/- 10 mm for EB
individuals, 65 +/- 4 mm for LB individuals, and 68 +/- 2 mm for sighted
blindfolded controls. These results support the hypothesis that (i) it exists a
trade-off between the development of enhanced perceptual abilities and role of
vision in the sound localization abilities of EB individuals, and (ii) the visual
information is fundamental in calibrating some aspects of the representation of
auditory space in the brain.
PMID- 26441734
TI - Movement plans for posture selection do not transfer across hands.
AB - In a sequential task, the grasp postures people select depend on their movement
history. This motor hysteresis effect results from the reuse of former movement
plans and reduces the cognitive cost of movement planning. Movement plans for
hand trajectories not only transfer across successive trials, but also across
hands. We therefore asked whether such a transfer would also be found in movement
plans for hand postures. To this end, we designed a sequential, continuous
posture selection task. Participants had to open a column of drawers with
cylindrical knobs in ascending and descending sequences. A hand switch was
required in each sequence. Hand pro/supination was analyzed directly before and
after the hand switch. Results showed that hysteresis effects were present
directly before, but absent directly after the hand switch. This indicates that,
in the current study, movement plans for hand postures only transfer across
trials, but not across hands.
PMID- 26441735
TI - Commentary: Why sprint interval training is inappropriate for a largely sedentary
population.
PMID- 26441736
TI - Response: Commentary "The sexualized-body-inversion hypothesis revisited: Valid
indicator of sexual objectification or methodological artifact?".
PMID- 26441737
TI - "Put your Hands up in the Air"? The interpersonal effects of pride and shame
expressions on opponents and teammates.
AB - The aim of the present research was to investigate the interpersonal effects of
pride and shame expressions amongst opponents and teammates in a soccer penalty
scenario. Across a series of experiments using the point-light method, pride and
shame expressions exerted strong effects upon observers' anticipated emotions,
associated cognitions, and performance expectations. Using the Implicit
Association Test (IAT) in two pilot studies we demonstrated that the created
pride and shame point-light stimuli were implicitly associated with status and
performance related attributes. In Experiment 1, observing pride expressions
caused opponents to anticipate more negative emotions, cognitions, and lower
performance expectancies toward their next performance in comparison with neutral
expressions. In contrast, pride expressions led teammates to anticipate more
positive emotions (i.e., pride and happiness), cognitions, and performance
expectations toward their next performance than neutral expressions (Experiments
2-4). The results are discussed within the emotions as social information (EASI,
Van Kleef, 2009) framework by arguing that the social context has to be taken
into account when investigating the interpersonal effects of emotion expressions.
In conclusion, the present research highlights the potential interpersonal
influence of the nonverbal expressions of pride and shame in soccer penalty
shootouts.
PMID- 26441738
TI - Investigating the ability to read others' intentions using humanoid robots.
AB - The ability to interact with other people hinges crucially on the possibility to
anticipate how their actions would unfold. Recent evidence suggests that a
similar skill may be grounded on the fact that we perform an action differently
if different intentions lead it. Human observers can detect these differences and
use them to predict the purpose leading the action. Although intention reading
from movement observation is receiving a growing interest in research, the
currently applied experimental paradigms have important limitations. Here, we
describe a new approach to study intention understanding that takes advantage of
robots, and especially of humanoid robots. We posit that this choice may overcome
the drawbacks of previous methods, by guaranteeing the ideal trade-off between
controllability and naturalness of the interactive scenario. Robots indeed can
establish an interaction in a controlled manner, while sharing the same action
space and exhibiting contingent behaviors. To conclude, we discuss the advantages
of this research strategy and the aspects to be taken in consideration when
attempting to define which human (and robot) motion features allow for intention
reading during social interactive tasks.
PMID- 26441739
TI - Explanatory model of emotional-cognitive variables in school mathematics
performance: a longitudinal study in primary school.
AB - This study tested a structural model of cognitive-emotional explanatory variables
to explain performance in mathematics. The predictor variables assessed were
related to students' level of development of early mathematical competencies
(EMCs), specifically, relational and numerical competencies, predisposition
toward mathematics, and the level of logical intelligence in a population of
primary school Chilean students (n = 634). This longitudinal study also included
the academic performance of the students during a period of 4 years as a
variable. The sampled students were initially assessed by means of an Early
Numeracy Test, and, subsequently, they were administered a Likert-type scale to
measure their predisposition toward mathematics (EPMAT) and a basic test of
logical intelligence. The results of these tests were used to analyse the
interaction of all the aforementioned variables by means of a structural
equations model. This combined interaction model was able to predict 64.3% of the
variability of observed performance. Preschool students' performance in EMCs was
a strong predictor for achievement in mathematics for students between 8 and 11
years of age. Therefore, this paper highlights the importance of EMCs and the
modulating role of predisposition toward mathematics. Also, this paper discusses
the educational role of these findings, as well as possible ways to improve
negative predispositions toward mathematical tasks in the school domain.
PMID- 26441740
TI - Visual perception can account for the close relation between numerosity
processing and computational fluency.
AB - Studies have shown that numerosity processing (e.g., comparison of numbers of
dots in two dot arrays) is significantly correlated with arithmetic performance.
Researchers have attributed this association to the fact that both tasks share
magnitude processing. The current investigation tested an alternative hypothesis,
which states that visual perceptual ability (as measured by a figure-matching
task) can account for the close relation between numerosity processing and
arithmetic performance (computational fluency). Four hundred and twenty four
third- to fifth-grade children (220 boys and 204 girls, 8.0-11.0 years old; 120
third graders, 146 fourth graders, and 158 fifth graders) were recruited from two
schools (one urban and one suburban) in Beijing, China. Six classes were randomly
selected from each school, and all students in each selected class participated
in the study. All children were given a series of cognitive and mathematical
tests, including numerosity comparison, figure matching, forward verbal working
memory, visual tracing, non-verbal matrices reasoning, mental rotation, choice
reaction time, arithmetic tests and curriculum-based mathematical achievement
test. Results showed that figure-matching ability had higher correlations with
numerosity processing and computational fluency than did other cognitive factors
(e.g., forward verbal working memory, visual tracing, non-verbal matrix
reasoning, mental rotation, and choice reaction time). More important,
hierarchical multiple regression showed that figure matching ability accounted
for the well-established association between numerosity processing and
computational fluency. In support of the visual perception hypothesis, the
results suggest that visual perceptual ability, rather than magnitude processing,
may be the shared component of numerosity processing and arithmetic performance.
PMID- 26441741
TI - Meta-analyses are no substitute for registered replications: a skeptical
perspective on religious priming.
AB - According to a recent meta-analysis, religious priming has a positive effect on
prosocial behavior (Shariff et al., 2015). We first argue that this meta-analysis
suffers from a number of methodological shortcomings that limit the conclusions
that can be drawn about the potential benefits of religious priming. Next we
present a re-analysis of the religious priming data using two different meta
analytic techniques. A Precision-Effect Testing-Precision-Effect-Estimate with
Standard Error (PET-PEESE) meta-analysis suggests that the effect of religious
priming is driven solely by publication bias. In contrast, an analysis using
Bayesian bias correction suggests the presence of a religious priming effect,
even after controlling for publication bias. These contradictory statistical
results demonstrate that meta-analytic techniques alone may not be sufficiently
robust to firmly establish the presence or absence of an effect. We argue that a
conclusive resolution of the debate about the effect of religious priming on
prosocial behavior - and about theoretically disputed effects more generally -
requires a large-scale, preregistered replication project, which we consider to
be the sole remedy for the adverse effects of experimenter bias and publication
bias.
PMID- 26441743
TI - Hedonic and eudaimonic well-being: the role of resilience beyond fluid
intelligence and personality traits.
AB - Resilience is a key factor in the well-being of individuals. The present study
set out to analyze the role of fluid intelligence, personality traits, and
resilience in hedonic and eudaimonic well-being (EWB) in order to determine the
incremental validity of resilience with respect to fluid intelligence and
personality traits in 168 Italian high school students. The Advanced Progressive
Matrices, the Big Five Questionnaire, the Connor-Davidson Resilience Scale, the
Satisfaction With Life Scale, the Positive and Negative Affect Schedule, the
Meaningful Life Measure, the Authenticity Scale were administered to the
participants in the study. The results showed that resilience added a significant
percentage of incremental variance with respect to fluid intelligence and
personality traits in relation to life satisfaction, positive affect, life
meaning, and authenticity. These results underline the value of resilience in
both hedonic and EWB, thus offering new perspectives for research and
intervention.
PMID- 26441742
TI - Efficient multitasking: parallel versus serial processing of multiple tasks.
AB - In the context of performance optimizations in multitasking, a central debate has
unfolded in multitasking research around whether cognitive processes related to
different tasks proceed only sequentially (one at a time), or can operate in
parallel (simultaneously). This review features a discussion of theoretical
considerations and empirical evidence regarding parallel versus serial task
processing in multitasking. In addition, we highlight how methodological
differences and theoretical conceptions determine the extent to which parallel
processing in multitasking can be detected, to guide their employment in future
research. Parallel and serial processing of multiple tasks are not mutually
exclusive. Therefore, questions focusing exclusively on either task-processing
mode are too simplified. We review empirical evidence and demonstrate that
shifting between more parallel and more serial task processing critically depends
on the conditions under which multiple tasks are performed. We conclude that
efficient multitasking is reflected by the ability of individuals to adjust
multitasking performance to environmental demands by flexibly shifting between
different processing strategies of multiple task-component scheduling.
PMID- 26441744
TI - Changes in aspects of social functioning depend upon prior changes in
neurodisability in people with acquired brain injury undergoing post-acute
neurorehabilitation.
AB - Post-acute community-based rehabilitation is effective in reducing disability.
However, while social participation and quality of life are valued as distal
outcomes of neurorehabilitation, it is often not possible to observe improvements
on these outcomes within the limited time-frames used in most investigations of
rehabilitation. The aim of the current study was to examine differences in the
sequence of attainments for people with acquired brain injury (ABI) undergoing
longer term post-acute neurorehabilitation. Participants with ABI who were
referred to comprehensive home and community-based neurorehabilitation were
assessed at induction to service, at 6 months and again at 1.5 years while still
in service on the Mayo-Portland Adaptability Index (MPAI-4), Community
Integration Questionnaire, Hospital Anxiety and Depression Scale, and World
Health Organisation Quality of Life measure. At 6 months post-induction to
service, significant differences were evident in MPAI abilities, adjustment, and
total neurodisability; and in anxiety and depression. By contrast, there was no
significant effect at 6 months on more socially oriented features of experience
namely quality of life (QoL), Community Integration and Participation. Eighteen
month follow-up showed continuation of the significant positive effects with the
addition of QoL-related to physical health, Psychological health, Social aspects
of QoL and Participation at this later time point. Regression analyses
demonstrated that change in QoL and Participation were dependent upon prior
changes in aspects of neurodisability. Age, severity or type of brain injury did
not significantly affect outcome. Results suggest that different constructs may
respond to neurorehabilitation at different time points in a dose effect manner,
and that change in social aspects of experience may be dependent upon the
specific nature of prior neurorehabilitation attainments.
PMID- 26441745
TI - Absence of modulatory action on haptic height perception with musical pitch.
AB - Although acoustic frequency is not a spatial property of physical objects, in
common language, pitch, i.e., the psychological correlated of frequency, is often
labeled spatially (i.e., "high in pitch" or "low in pitch"). Pitch-height is
known to modulate (and interact with) the response of participants when they are
asked to judge spatial properties of non-auditory stimuli (e.g., visual) in a
variety of behavioral tasks. In the current study we investigated whether the
modulatory action of pitch-height extended to the haptic estimation of height of
a virtual step. We implemented a HW/SW setup which is able to render virtual 3D
objects (stair-steps) haptically through a PHANTOM device, and to provide real
time continuous auditory feedback depending on the user interaction with the
object. The haptic exploration was associated with a sinusoidal tone whose pitch
varied as a function of the interaction point's height within (i) a narrower and
(ii) a wider pitch range, or (iii) a random pitch variation acting as a control
audio condition. Explorations were also performed with no sound (haptic only).
Participants were instructed to explore the virtual step freely, and to
communicate height estimation by opening their thumb and index finger to mimic
the step riser height, or verbally by reporting the height in centimeters of the
step riser. We analyzed the role of musical expertise by dividing participants
into non-musicians and musicians. Results showed no effects of musical pitch on
high-realistic haptic feedback. Overall there is no difference between the two
groups in the proposed multimodal conditions. Additionally, we observed a
different haptic response distribution between musicians and non-musicians when
estimations of the auditory conditions are matched with estimations in the no
sound condition.
PMID- 26441746
TI - Opinion: Paradigms, methods, and the (as yet) failed striving for methodological
diversity in educational psychology published research.
PMID- 26441747
TI - Gender differences in experiential and facial reactivity to approval and
disapproval during emotional social interactions.
AB - Negative social evaluations represent social threats and elicit negative emotions
such as anger or fear. Positive social evaluations, by contrast, may increase
self-esteem and generate positive emotions such as happiness and pride. Gender
differences are likely to shape both the perception and expression of positive
and negative social evaluations. Yet, current knowledge is limited by a reliance
on studies that used static images of individual expressers with limited external
validity. Furthermore, only few studies considered gender differences on both the
expresser and perceiver side. The present study approached these limitations by
utilizing a naturalistic stimulus set displaying nine males and nine females
(expressers) delivering social evaluative sentences to 32 female and 26 male
participants (perceivers). Perceivers watched 30 positive, 30 negative, and 30
neutral messages while facial electromyography (EMG) was continuously recorded
and subjective ratings were obtained. Results indicated that men expressing
positive evaluations elicited stronger EMG responses in both perceiver genders.
Arousal was rated higher when positive evaluations were expressed by the opposite
gender. Thus, gender differences need to be more explicitly considered in
research of social cognition and affective science using naturalistic social
stimuli.
PMID- 26441748
TI - Wearing weighted backpack dilates subjective visual duration: the role of
functional linkage between weight experience and visual timing.
AB - Bodily state plays a critical role in our perception. In the present study, we
asked the question whether and how bodily experience of weights influences time
perception. Participants judged durations of a picture (a backpack or a trolley
bag) presented on the screen, while wearing different weight backpacks or without
backpack. The results showed that the subjective duration of the backpack picture
was dilated when participants wore a medium weighted backpack relative to an
empty backpack or without backpack, regardless of identity (e.g., color) of the
visual backpack. However, the duration dilation was not manifested for the
picture of trolley bag. These findings suggest that weight experience modulates
visual duration estimation through the linkage between the wore backpack and to
be-estimated visual target. The congruent action affordance between the wore
backpack and visual inputs plays a critical role in the functional linkage
between inner experience and time perception. We interpreted our findings within
the framework of embodied time perception.
PMID- 26441749
TI - The Bergen Shopping Addiction Scale: reliability and validity of a brief
screening test.
AB - Although excessive and compulsive shopping has been increasingly placed within
the behavioral addiction paradigm in recent years, items in existing screens
arguably do not assess the core criteria and components of addiction. To date,
assessment screens for shopping disorders have primarily been rooted within the
impulse-control or obsessive-compulsive disorder paradigms. Furthermore, existing
screens use the terms 'shopping,' 'buying,' and 'spending' interchangeably, and
do not necessarily reflect contemporary shopping habits. Consequently, a new
screening tool for assessing shopping addiction was developed. Initially, 28
items, four for each of seven addiction criteria (salience, mood modification,
conflict, tolerance, withdrawal, relapse, and problems), were constructed. These
items and validated scales (i.e., Compulsive Buying Measurement Scale, Mini
International Personality Item Pool, Hospital Anxiety and Depression Scale,
Rosenberg Self-Esteem Scale) were then administered to 23,537 participants (M age
= 35.8 years, SD age = 13.3). The highest loading item from each set of four
pooled items reflecting the seven addiction criteria were retained in the final
scale, The Bergen Shopping Addiction Scale (BSAS). The factor structure of the
BSAS was good (RMSEA = 0.064, CFI = 0.983, TLI = 0.973) and coefficient alpha was
0.87. The scores on the BSAS converged with scores on the Compulsive Buying
Measurement Scale (CBMS; 0.80), and were positively correlated with extroversion
and neuroticism, and negatively with conscientiousness, agreeableness, and
intellect/imagination. The scores of the BSAS were positively associated with
anxiety, depression, and low self-esteem and inversely related to age. Females
scored higher than males on the BSAS. The BSAS is the first scale to fully embed
shopping addiction within an addiction paradigm. A recommended cutoff score for
the new scale and future research directions are discussed.
PMID- 26441750
TI - Cognitive synergy in groups and group-to-individual transfer of decision-making
competencies.
AB - In a field study (148 participants organized in 38 groups) we tested the effect
of group synergy and one's position in relation to the collaborative zone of
proximal development (CZPD) on the change of individual decision-making
competencies. We used two parallel sets of decision tasks reported in previous
research to test rationality and we evaluated individual decision-making
competencies in the pre-group and post-group conditions as well as group
rationality (as an emergent group level phenomenon). We used multilevel modeling
to analyze the data and the results showed that members of synergetic groups had
a higher cognitive gain as compared to members of non-synergetic groups, while
highly rational members (members above the CZPD) had lower cognitive gains
compared to less rational group members (members situated below the CZPD). These
insights extend the literature on group-to-individual transfer of learning and
have important practical implications as they show that group dynamics influence
the development of individual decision-making competencies.
PMID- 26441751
TI - Brain readiness and the nature of language.
AB - To identify the neural components that make a brain ready for language, it is
important to have well defined linguistic phenotypes, to know precisely what
language is. There are two central features to language: the capacity to form
signs (words), and the capacity to combine them into complex structures. We must
determine how the human brain enables these capacities. A sign is a link between
a perceptual form and a conceptual meaning. Acoustic elements and content
elements, are already brain-internal in non-human animals, but as categorical
systems linked with brain-external elements. Being indexically tied to objects of
the world, they cannot freely link to form signs. A crucial property of a
language-ready brain is the capacity to process perceptual forms and contents
offline, detached from any brain-external phenomena, so their "representations"
may be linked into signs. These brain systems appear to have pleiotropic effects
on a variety of phenotypic traits and not to be specifically designed for
language. Syntax combines signs, so the combination of two signs operates
simultaneously on their meaning and form. The operation combining the meanings
long antedates its function in language: the primitive mode of predication
operative in representing some information about an object. The combination of
the forms is enabled by the capacity of the brain to segment vocal and visual
information into discrete elements. Discrete temporal units have order and
juxtaposition, and vocal units have intonation, length, and stress. These are
primitive combinatorial processes. So the prior properties of the physical and
conceptual elements of the sign introduce combinatoriality into the linguistic
system, and from these primitive combinatorial systems derive concatenation in
phonology and combination in morphosyntax. Given the nature of language, a key
feature to our understanding of the language-ready brain is to be found in the
mechanisms in human brains that enable the unique means of representation that
allow perceptual forms and contents to be linked into signs.
PMID- 26441753
TI - Manipulating target size influences perceptions of success when learning a dart
throwing skill but does not impact retention.
AB - Positive feedback or experiences of success during skill acquisition have been
shown to benefit motor skill learning. In this study, our aim was to manipulate
learners' success perceptions through a minor adjustment to goal criterion
(target size) in a dart-throwing task. Two groups of novice participants
practiced throwing at a large (easy) or a small (difficult) target from the same
distance. In reference to the origin/center of the target, the practice targets
were alike in objective difficulty and indeed participants in both groups were
not different in their objective practice performance (i.e., radial error from
the center). Although the groups experienced markedly different success rates,
with the large target group experiencing more hits and reporting greater
confidence (or self-efficacy) than the small target group, these practice effects
were not carried into longer-term retention, which was assessed after a 1-week
delay. For success perceptions to moderate or benefit motor learning, we argue
that unambiguous indicators of positive performance are necessary, especially for
tasks where intrinsic feedback about objective error is salient.
PMID- 26441754
TI - Answering research questions without calculating the mean.
PMID- 26441752
TI - FRAS1-related extracellular matrix 3 (FREM3) single-nucleotide polymorphism
effects on gene expression, amygdala reactivity and perceptual processing speed:
An accelerated aging pathway of depression risk.
AB - The A allele of the FRAS1-related extracellular matrix protein 3 (FREM3)
rs7676614 single nucleotide polymorphism (SNP) was linked to major depressive
disorder (MDD) in an early genome-wide association study (GWAS), and to symptoms
of psychomotor retardation in a follow-up investigation. In line with significant
overlap between age- and depression-related molecular pathways, parallel work has
shown that FREM3 expression in postmortem human brain decreases with age. Here,
we probe the effect of rs7676614 on amygdala reactivity and perceptual processing
speed, both of which are altered in depression and aging. Amygdala reactivity was
assessed using a face-matching BOLD fMRI paradigm in 365 Caucasian participants
in the Duke Neurogenetics Study (DNS) (192 women, mean age 19.7 +/- 1.2).
Perceptual processing speed was indexed by reaction times in the same task and
the Trail Making Test (TMT). The effect of rs7676614 on FREM3 mRNA brain
expression levels was probed in a postmortem cohort of 169 Caucasian individuals
(44 women, mean age 50.8 +/- 14.9). The A allele of rs7676614 was associated with
blunted amygdala reactivity to faces, slower reaction times in the face-matching
condition (p < 0.04), as well as marginally slower performance on TMT Part B (p =
0.056). In the postmortem cohort, the T allele of rs6537170 (proxy for the
rs7676614 A allele), was associated with trend-level reductions in gene
expression in Brodmann areas 11 and 47 (p = 0.066), reminiscent of patterns
characteristic of older age. The low-expressing allele of another FREM3 SNP
(rs1391187) was similarly associated with reduced amygdala reactivity and slower
TMT Part B speed, in addition to reduced BA47 activity and extraversion (p <
0.05). Together, these results suggest common genetic variation associated with
reduced FREM3 expression may confer risk for a subtype of depression
characterized by reduced reactivity to environmental stimuli and slower
perceptual processing speed, possibly suggestive of accelerated aging.
PMID- 26441755
TI - Moral asymmetries in judgments of agency withstand ludicrous causal deviance.
AB - Americans have been shown to attribute greater intentionality to immoral than to
amoral actions in cases of causal deviance, that is, cases where a goal is
satisfied in a way that deviates from initially planned means (e.g., a gunman
wants to hit a target and his hand slips, but the bullet ricochets off a rock
into the target). However, past research has yet to assess whether this asymmetry
persists in cases of extreme causal deviance. Here, we manipulated the level of
mild to extreme causal deviance of an immoral versus amoral act. The asymmetry in
attributions of intentionality was observed at all but the most extreme level of
causal deviance, and, as we hypothesized, was mediated by attributions of
blame/credit and judgments of action performance. These findings are discussed as
they support a multiple-concepts interpretation of the asymmetry, wherein blame
renders a naive concept of intentional action (the outcome matches the intention)
more salient than a composite concept (the outcome matches the intention and was
brought about by planned means), and in terms of their implications for cross
cultural research on judgments of agency.
PMID- 26441756
TI - There or not there? A multidisciplinary review and research agenda on the impact
of transparent barriers on human perception, action, and social behavior.
AB - Through advances in production and treatment technologies, transparent glass has
become an increasingly versatile material and a global hallmark of modern
architecture. In the shape of invisible barriers, it defines spaces while
simultaneously shaping their lighting, noise, and climate conditions. Despite
these unique architectural qualities, little is known regarding the human
experience with glass barriers. Is a material that has been described as being
simultaneously there and not there from an architectural perspective, actually
there and/or not there from perceptual, behavioral, and social points of view? In
this article, we review systematic observations and experimental studies that
explore the impact of transparent barriers on human cognition and action. In
doing so, the importance of empirical and multidisciplinary approaches to inform
the use of glass in contemporary architecture is highlighted and key questions
for future inquiry are identified.
PMID- 26441757
TI - The sweetest thing: the influence of angularity, symmetry, and the number of
elements on shape-valence and shape-taste matches.
AB - A within-participants experiment was conducted in two countries (the UK and
Colombia) in order to investigate the matching of shapes to taste words.
Comparing the two countries allowed us to explore some of the cultural
differences that have been reported thus far solely in terms of people's visual
preferences. In particular, we addressed the question of whether properties other
than angularity influence shape-valence and shape-taste matching (crossmodal
correspondences). The participants in the present study repeatedly matched eight
shapes, varying in terms of their angularity, symmetry, and number of elements to
one of two words-pleasant or unpleasant and sweet or sour. Participants' choices,
as well as the latency of their responses, and their hand movements, were
evaluated. The participants were more likely to judge those shapes that were
rounder, symmetrical, and those shapes that had fewer elements as both pleasant
and sweet. Those shapes that were more angular, asymmetrical, and that had a
greater number of elements, were more likely to be judged as both unpleasant and
sour instead. The evidence presented here therefore suggests that aside from
angularity and roundness, both symmetry/asymmetry and the number of elements
present in a shape also influence valence and taste categorizations.
PMID- 26441759
TI - Corrigendum: Tactile input and empathy modulate the perception of ambiguous
biological motion.
AB - [This corrects the article on p. 161 in vol. 6, PMID: 25750631.].
PMID- 26441758
TI - How do different components of Effortful Control contribute to children's
mathematics achievement?
AB - This work sought to investigate the specific contribution of two different
components of Effortful Control (EC) -attentional focusing (AF) and inhibitory
control- to children's mathematics achievement. The sample was composed of 142
children aged 9-12 year-old. EC components were measured through the Temperament
in Middle Childhood Questionnaire (TMCQ; parent's report); math achievement was
measured via teacher's report and through the standard Woodcock-Johnson test.
Additionally, the contribution of other cognitive and socio-emotional processes
was taken into account. Our results showed that only AF significantly contributed
to the variance of children's mathematics achievement; interestingly, mediational
models showed that the relationship between effortful attentional self-regulation
and mathematics achievement was mediated by academic peer popularity, as well as
by intelligence and study skills. Results are discussed in the light of the
current theories on the role of children's self-regulation abilities in the
context of school.
PMID- 26441761
TI - Automated facial coding software outperforms people in recognizing neutral faces
as neutral from standardized datasets.
AB - Little is known about people's accuracy of recognizing neutral faces as neutral.
In this paper, I demonstrate the importance of knowing how well people recognize
neutral faces. I contrasted human recognition scores of 100 typical, neutral
front-up facial images with scores of an arguably objective judge - automated
facial coding (AFC) software. I hypothesized that the software would outperform
humans in recognizing neutral faces because of the inherently objective nature of
computer algorithms. Results confirmed this hypothesis. I provided the first-ever
evidence that computer software (90%) was more accurate in recognizing neutral
faces than people were (59%). I posited two theoretical mechanisms, i.e., smile
as-a-baseline and false recognition of emotion, as possible explanations for my
findings.
PMID- 26441760
TI - Source unreliability decreases but does not cancel the impact of social
information on metacognitive evaluations.
AB - Through metacognitive evaluations, individuals assess their own cognitive
operations with respect to their current goals. We have previously shown that non
verbal social cues spontaneously influence these evaluations, even when the cues
are unreliable. Here, we explore whether a belief about the reliability of the
source can modulate this form of social impact. Participants performed a two
alternative forced choice task that varied in difficulty. The task was followed
by a video of a person who was presented as being either competent or incompetent
at performing the task. That person provided random feedback to the participant
through facial expressions indicating agreement, disagreement or uncertainty.
Participants then provided a metacognitive evaluation by rating their confidence
in their answer. Results revealed that participants' confidence was higher
following agreements. Interestingly, this effect was merely reduced but not
canceled for the incompetent individual, even though participants were able to
perceive the individual's incompetence. Moreover, perceived agreement induced
zygomaticus activity, but only when the feedback was provided for difficult
trials by the competent individual. This last result strongly suggests that
people implicitly appraise the relevance of social feedback with respect to their
current goal. Together, our findings suggest that people always integrate social
agreement into their metacognitive evaluations, even when epistemic vigilance
mechanisms alert them to the risk of being misinformed.
PMID- 26441762
TI - Looking at the evidence in visual world: eye-movements reveal how bilingual and
monolingual Turkish speakers process grammatical evidentiality.
AB - This study presents pioneering data on how adult early bilinguals (heritage
speakers) and late bilingual speakers of Turkish and German process grammatical
evidentiality in a visual world setting in comparison to monolingual speakers of
Turkish. Turkish marks evidentiality, the linguistic reference to information
source, through inflectional affixes signaling either direct (-DI) or indirect (
mIs) evidentiality. We conducted an eye-tracking-during-listening experiment
where participants were given access to visual 'evidence' supporting the use of
either a direct or indirect evidential form. The behavioral results indicate that
the monolingual Turkish speakers comprehended direct and indirect evidential
scenarios equally well. In contrast, both late and early bilinguals were less
accurate and slower to respond to direct than to indirect evidentials. The
behavioral results were also reflected in the proportions of looks data. That is,
both late and early bilinguals fixated less frequently on the target picture in
the direct than in the indirect evidential condition while the monolinguals
showed no difference between these conditions. Taken together, our results
indicate reduced sensitivity to the semantic and pragmatic function of direct
evidential forms in both late and early bilingual speakers, suggesting a
simplification of the Turkish evidentiality system in Turkish heritage grammars.
We discuss our findings with regard to theories of incomplete acquisition and
first language attrition.
PMID- 26441763
TI - Gender stereotypes across the ages: On-line processing in school-age children,
young and older adults.
AB - Most research to date on implicit gender stereotyping has been conducted with one
age group - young adults. The mechanisms that underlie the on-line processing of
stereotypical information in other age groups have received very little
attention. This is the first study to investigate real time processing of gender
stereotypes at different age levels. We investigated the activation of gender
stereotypes in Italian in four groups of participants: third- and fifth-graders,
young and older adults. Participants heard a noun that was stereotypically
associated with masculine (preside "headmaster") or feminine roles (badante
"social care worker"), followed by a male (padre "father") or female kinship term
(madre "mother"). The task was to decide if the two words - the role noun and the
kinship term - could describe the same person. Across all age groups,
participants were significantly faster to respond, and significantly more likely
to press 'yes,' when the gender of the target was congruent with the
stereotypical gender use of the preceding prime. These findings suggest that
information about the stereotypical gender associated with a role noun is
incorporated into the mental representation of this word and is activated as soon
as the word is heard. In addition, our results show differences between male and
female participants of the various age groups, and between male- and female
oriented stereotypes, pointing to important gender asymmetries.
PMID- 26441764
TI - A word on standardization in longitudinal studies: don't.
PMID- 26441765
TI - Speech intelligibility and recall of first and second language words heard at
different signal-to-noise ratios.
AB - Free recall of spoken words in Swedish (native tongue) and English were assessed
in two signal-to-noise ratio (SNR) conditions (+3 and +12 dB), with and without
half of the heard words being repeated back orally directly after presentation
[shadowing, speech intelligibility (SI)]. A total of 24 word lists with 12 words
each were presented in English and in Swedish to Swedish speaking college
students. Pre-experimental measures of working memory capacity (operation span,
OSPAN) were taken. A basic hypothesis was that the recall of the words would be
impaired when the encoding of the words required more processing resources,
thereby depleting working memory resources. This would be the case when the SNR
was low or when the language was English. A low SNR was also expected to impair
SI, but we wanted to compare the sizes of the SNR-effects on SI and recall. A low
score on working memory capacity was expected to further add to the negative
effects of SNR and language on both SI and recall. The results indicated that SNR
had strong effects on both SI and recall, but also that the effect size was
larger for recall than for SI. Language had a main effect on recall, but not on
SI. The shadowing procedure had different effects on recall of the early and late
parts of the word lists. Working memory capacity was unimportant for the effect
on SI and recall. Thus, recall appear to be a more sensitive indicator than SI
for the acoustics of learning, which has implications for building codes and
recommendations concerning classrooms and other workplaces, where both hearing
and learning is important.
PMID- 26441766
TI - The effect of a brief mindfulness induction on processing of emotional images: an
ERP study.
AB - The ability to effectively direct one's attention is an important aspect of
regulating emotions and a component of mindfulness. Mindfulness practices have
been established as effective interventions for mental and physical illness;
however, the underlying neural mechanisms of mindfulness and how they relate to
emotional processing have not been explored in depth. The current study used a
within-subjects repeated measures design to examine if focused breathing, a brief
mindfulness induction, could modulate event-related potentials (ERPs) during
emotional image processing relative to a control condition. We related ERP
measures of processing positive, negative, and neutral images (the P300 and late
positive potential - LPP) to state and trait mindfulness measures. Overall, the
brief mindfulness induction condition did not influence ERPs reflecting emotional
processing; however, in the brief mindfulness induction condition, those
participants who reported feeling more decentered (a subscale of the Toronto
Mindfulness Scale) after viewing the images had reduced P300 responses to
negative versus neutral images.
PMID- 26441767
TI - The power of putting a label on it: green labels weigh heavier than contradicting
product information for consumers' purchase decisions and post-purchase behavior.
AB - Green products are appealing. Thus, labeling products as environmentally friendly
is an effective strategy to increase sales. However, the labels often promise
more than the products can actually deliver. In the present research, we examined
the expectation that consumers with high ecological motivation have strong
preferences for green-labeled products - even when presented product information
contradicts the label's image. This unsettling hypothesis is grounded in the
labels' potential to create a cognitive match between the labeled product and
consumers' motives. For labels indicating environmental friendliness (green
product labels), this link should be strongest when consumers' ecological
motivation is high. Findings in a series of three experiments support our
assumption, showing that consumers with high ecological motivation had strong
preferences (i.e., product evaluations, purchase intentions, and simulated
purchase decisions) for green-labeled products as compared to consumers with low
ecological motivation (Studies 1-3). Crucially, these preferences were robust,
despite contradicting environmental product information (Studies 1 and 2). We
extended our findings by additionally examining the impact of product labels and
motivation on moral self-regulation processes. This was established by assessing
participants' pro-social behavior after the purchase task: participants with high
ecological motivation acted, consistent with their motives, more pro-socially in
post-decision occasions. In accordance with moral cleansing effects, pro-social
behavior was intensified after purchasing conventional products (Studies 2 and
3). Green labels protected participants with high ecological motivation from
moral threats due to the purchase, thus making pro-social behavior less likely.
Findings suggest that highly ecologically motivated consumers are most
susceptible to green labels, which may override detailed product information.
PMID- 26441768
TI - Dream-reality confusion in borderline personality disorder: a theoretical
analysis.
AB - This paper presents an analysis of dream-reality confusion (DRC) in relation to
the characteristics of borderline personality disorder (BPD), based on research
findings and theoretical considerations. It is hypothesized that people with BPD
are more likely to experience DRC compared to people in non-clinical population.
Several variables related to this hypothesis were identified through a
theoretical analysis of the scientific literature. Sleep disturbances: problems
with sleep are found in 15-95.5% of people with BPD (Hafizi, 2013), and unstable
sleep and wake cycles, which occur in BPD (Fleischer et al., 2012), are linked to
DRC. Dissociation: nearly two-thirds of people with BPD experience dissociative
symptoms (Korzekwa and Pain, 2009) and dissociative symptoms are correlated with
a fantasy proneness; both dissociative symptoms and fantasy proneness are related
to DRC (Giesbrecht and Merckelbach, 2006). Negative dream content: People with
BPD have nightmares more often than other people (Semiz et al., 2008); dreams
that are more likely to be confused with reality tend to be more realistic and
unpleasant, and are reflected in waking behavior (Rassin et al., 2001). Cognitive
disturbances: Many BPD patients experience various cognitive disturbances,
including problems with reality testing (Fiqueierdo, 2006; Mosquera et al.,
2011), which can foster DRC. Thin boundaries: People with thin boundaries are
more prone to DRC than people with thick boundaries, and people with BPD tend to
have thin boundaries (Hartmann, 2011). The theoretical analysis on the basis of
these findings suggests that people who suffer from BPD may be more susceptible
to confusing dream content with actual waking events.
PMID- 26441770
TI - Polish pseudo-words list: dataset of 3023 stimuli with competent judges' ratings.
AB - Pseudo-words are stimuli, which are useful in research concerning lexical
processing. As in the case of existing words, they are language dependent; thus,
they should be generated for each language separately. The Polish Pseudo-words
List (PPwL) is a dataset presenting a set of 3023 stimuli (words of 4-13 letters
long). They were generated using an algorithm substituting random letters in
existing words with respect to the frequency of letters in certain positions. We
put out the raw set for a competent judges' assessment and included the responses
in the dataset. PPwL allows the choice of suitable control stimuli for
experiments concerning lexical processing.
PMID- 26441769
TI - Associations between speech understanding and auditory and visual tests of verbal
working memory: effects of linguistic complexity, task, age, and hearing loss.
AB - Listeners with hearing loss commonly report having difficulty understanding
speech, particularly in noisy environments. Their difficulties could be due to
auditory and cognitive processing problems. Performance on speech-in-noise tests
has been correlated with reading working memory span (RWMS), a measure often
chosen to avoid the effects of hearing loss. If the goal is to assess the
cognitive consequences of listeners' auditory processing abilities, however, then
listening working memory span (LWMS) could be a more informative measure. Some
studies have examined the effects of different degrees and types of masking on
working memory, but less is known about the demands placed on working memory
depending on the linguistic complexity of the target speech or the task used to
measure speech understanding in listeners with hearing loss. Compared to RWMS,
LWMS measures using different speech targets and maskers may provide a more
ecologically valid approach. To examine the contributions of RWMS and LWMS to
speech understanding, we administered two working memory measures (a traditional
RWMS measure and a new LWMS measure), and a battery of tests varying in the
linguistic complexity of the speech materials, the presence of babble masking,
and the task. Participants were a group of younger listeners with normal hearing
and two groups of older listeners with hearing loss (n = 24 per group). There was
a significant group difference and a wider range in performance on LWMS than on
RWMS. There was a significant correlation between both working memory measures
only for the oldest listeners with hearing loss. Notably, there were only few
significant correlations among the working memory and speech understanding
measures. These findings suggest that working memory measures reflect individual
differences that are distinct from those tapped by these measures of speech
understanding.
PMID- 26441771
TI - Electrophysiology of subject-verb agreement mediated by speakers' gender.
AB - An important property of speech is that it explicitly conveys features of a
speaker's identity such as age or gender. This event-related potential (ERP)
study examined the effects of social information provided by a speaker's gender,
i.e., the conceptual representation of gender, on subject-verb agreement. Despite
numerous studies on agreement, little is known about syntactic computations
generated by speaker characteristics extracted from the acoustic signal. Slovak
is well suited to investigate this issue because it is a morphologically rich
language in which agreement involves features for number, case, and gender.
Grammaticality of a sentence can be evaluated by checking a speaker's gender as
conveyed by his/her voice. We examined how conceptual information about speaker
gender, which is not syntactic but rather social and pragmatic in nature, is
interpreted for the computation of agreement patterns. ERP responses to verbs
disagreeing with the speaker's gender (e.g., a sentence including a masculine
verbal inflection spoken by a female person 'the neighbors were upset because I
(*)stoleMASC plums') elicited a larger early posterior negativity compared to
correct sentences. When the agreement was purely syntactic and did not depend on
the speaker's gender, a disagreement between a formally marked subject and the
verb inflection (e.g., the womanFEM (*)stoleMASC plums) resulted in a larger P600
preceded by a larger anterior negativity compared to the control sentences. This
result is in line with proposals according to which the recruitment of non
syntactic information such as the gender of the speaker results in N400-like
effects, while formally marked syntactic features lead to structural integration
as reflected in a LAN/P600 complex.
PMID- 26441772
TI - Infant discrimination of humanoid robots.
AB - Recently, extremely humanlike robots called "androids" have been developed, some
of which are already being used in the field of entertainment. In the context of
psychological studies, androids are expected to be used in the future as fully
controllable human stimuli to investigate human nature. In this study, we used an
android to examine infant discrimination ability between human beings and non
human agents. Participants (N = 42 infants) were assigned to three groups based
on their age, i.e., 6- to 8-month-olds, 9- to 11-month-olds, and 12- to 14-month
olds, and took part in a preferential looking paradigm. Of three types of agents
involved in the paradigm-a human, an android modeled on the human, and a
mechanical-looking robot made from the android-two at a time were presented side
by-side as they performed a grasping action. Infants' looking behavior was
measured using an eye tracking system, and the amount of time spent focusing on
each of three areas of interest (face, goal, and body) was analyzed. Results
showed that all age groups predominantly looked at the robot and at the face
area, and that infants aged over 9 months watched the goal area for longer than
the body area. There was no difference in looking times and areas focused on
between the human and the android. These findings suggest that 6- to 14-month
olds are unable to discriminate between the human and the android, although they
can distinguish the mechanical robot from the human.
PMID- 26441773
TI - Embodiment and enculturation: the future of architectural design.
AB - A half-century ago the Dutch architect Aldo van Eyck encouraged designers to
think about "space and time" not as abstractions in themselves but rather as
cultural events better approached through the medium of "place and occasion." Van
Eyck made this point on the basis of his own travels and through his extensive
readings in cultural anthropology, and his prescience is only now acquiring the
credibility that it deserves through the work of a multitude of interdisciplinary
researchers. Phenomenologists argue that we are embodied organisms-acting-within
environments, and these inhabiting abodes are constructed of both material and
cultural dimensions. We are thus preeminently social in our range of self
consciousness, and intensely ceremonial in every facet of our being. Evolutionary
psychologists and anthropologists are currently locating the origin and
development of our most basic social behaviors far in our pre-human past;
neuroscientists are today modeling our social circuits in the deepest reaches of
our brains. Architecture would gain much from an updated cultural theory grounded
in these new models of human existence.
PMID- 26441774
TI - Interpersonal trust: an event-based account.
PMID- 26441775
TI - Gender inequalities in the workplace: the effects of organizational structures,
processes, practices, and decision makers' sexism.
AB - Gender inequality in organizations is a complex phenomenon that can be seen in
organizational structures, processes, and practices. For women, some of the most
harmful gender inequalities are enacted within human resources (HRs) practices.
This is because HR practices (i.e., policies, decision-making, and their
enactment) affect the hiring, training, pay, and promotion of women. We propose a
model of gender discrimination in HR that emphasizes the reciprocal nature of
gender inequalities within organizations. We suggest that gender discrimination
in HR-related decision-making and in the enactment of HR practices stems from
gender inequalities in broader organizational structures, processes, and
practices. This includes leadership, structure, strategy, culture, organizational
climate, as well as HR policies. In addition, organizational decision makers'
levels of sexism can affect their likelihood of making gender biased HR-related
decisions and/or behaving in a sexist manner while enacting HR practices.
Importantly, institutional discrimination in organizational structures,
processes, and practices play a pre-eminent role because not only do they affect
HR practices, they also provide a socializing context for organizational decision
makers' levels of hostile and benevolent sexism. Although we portray gender
inequality as a self-reinforcing system that can perpetuate discrimination,
important levers for reducing discrimination are identified.
PMID- 26441776
TI - Children's spontaneous emotional expressions while receiving (un)wanted prizes in
the presence of peers.
AB - Although current emotion theories emphasize the importance of contextual factors
for emotional expressive behavior, developmental studies that examine such
factors are currently thin on the ground. In this research, we studied the course
of emotional expressions of 8- and 11-year-old children after winning a (large)
first prize or a (substantially smaller) consolation prize, while playing a game
competing against the computer or a physically co-present peer. We analyzed their
emotional reactions by conducting two perception tests in which participants
rated children's level of happiness. Results showed that co-presence positively
affected children's happiness only when receiving the first prize. Moreover, for
children who were in the presence of a peer, we found that eye contact affected
children's expressions of happiness, but that the effect was different for
different age groups: 8-year-old children were negatively affected, and 11-year
old children positively. Overall, we can conclude that as children grow older and
their social awareness increases, the presence of a peer affects their non-verbal
expressions, regardless of their appreciation of their prize.
PMID- 26441778
TI - Gender stereotype endorsement differentially predicts girls' and boys' trait
state discrepancy in math anxiety.
AB - Mathematics is associated with anxiety for many students; an emotion linked to
lower well-being and poorer learning outcomes. While findings typically show
females to report higher trait math anxiety than males, no gender differences
have to date been found in state (i.e., momentary) math anxiety. The present
diary study aimed to replicate previous findings in investigating whether levels
of academic self-concept was related to this discrepancy in trait vs. state
anxiety measures. Additionally, mathematics-related gender stereotype endorsement
(mathematics is a male domain) was investigated as an additional predictor of the
trait-state discrepancy. The sample included 755 German 9th and 10th graders who
completed self-report measures of trait math anxiety, math self-concept, and
gender stereotype endorsement, in addition to state measures of anxiety after
math classes by use of a standardized diary for 2-3 weeks (N within = 6207). As
expected, females reported higher trait math anxiety but no gender differences
were found for state math anxiety. Also in line with our assumptions, multilevel
analyses showed the discrepancy between trait and state anxiety to be negatively
related to students' self-concept (i.e., a lower discrepancy for students with
higher self-concepts). Furthermore, gender stereotype endorsement differentially
predicted the trait-state discrepancy: When controlling for self-concept in
mathematics, females who endorsed the gender stereotype of math being a male
domain more strongly overestimated their trait math anxiety as compared to their
state anxiety whereas this effect was not significant for males. The present
findings suggest that gender stereotype endorsement plays an important role in
explaining gender differences in math anxiety above and beyond academic self
concept. Implications for future research and educational practice are discussed.
PMID- 26441779
TI - The use of personalized behavioral feedback for online gamblers: an empirical
study.
AB - Over the last few years, online gambling has become a more common leisure time
activity. However, for a small minority, the activity can become problematic.
Consequently, the gambling industry has started to acknowledge their role in
player protection and harm minimization and some gambling companies have
introduced responsible gambling tools as a way of helping players stay in
control. The present study evaluated the effectiveness of mentor (a responsible
gambling tool that provides personalized feedback to players) among 1,015 online
gamblers at a European online gambling site, and compared their behavior with
matched controls (n = 15,216) on the basis of age, gender, playing duration, and
theoretical loss (i.e., the amount of money wagered multiplied by the payout
percentage of a specific game played). The results showed that online gamblers
receiving personalized feedback spent significantly less time and money gambling
compared to controls that did not receive personalized feedback. The results
suggest that responsible gambling tools providing personalized feedback may help
the clientele of gambling companies gamble more responsibly, and may be of help
those who gamble excessively to stay within their personal time and money
spending limits.
PMID- 26441780
TI - Interoception and the uneasiness of the mind: affect as perceptual style.
AB - Autonomous system models of interoception describe perception of bodily
sensations as an active process in which the brain generates and tests hypotheses
about the body on the basis of proximal information. This view of perception as
inference allows a new perspective on the role of affect in perception. Affect
and interoception are closely linked, but processes underlying this link are
poorly understood. We suggest that a predictive coding perspective allows
acknowledging affect as integral part of information processing. We outline how
affect may intrinsically modify processes of interoception by acting as threshold
mechanism in stimulus grouping and information compression. We outline how well
established methods, for example, from categorization research may allow
quantifying this influence of affect on perception in empirical tests of
predictive coding models. We discuss how this may enrich the study of the
relationship between affect and interoception and may have important clinical
relevance.
PMID- 26441777
TI - The contributions of vision and haptics to reaching and grasping.
AB - This review aims to provide a comprehensive outlook on the sensory (visual and
haptic) contributions to reaching and grasping. The focus is on studies in
developing children, normal, and neuropsychological populations, and in sensory
deprived individuals. Studies have suggested a right-hand/left-hemisphere
specialization for visually guided grasping and a left-hand/right-hemisphere
specialization for haptically guided object recognition. This poses the
interesting possibility that when vision is not available and grasping relies
heavily on the haptic system, there is an advantage to use the left hand. We
review the evidence for this possibility and dissect the unique contributions of
the visual and haptic systems to grasping. We ultimately discuss how the
integration of these two sensory modalities shape hand preference.
PMID- 26441782
TI - Imitation by combination: preschool age children evidence summative imitation in
a novel problem-solving task.
AB - Children are exceptional, even 'super,' imitators but comparatively poor
independent problem-solvers or innovators. Yet, imitation and innovation are both
necessary components of cumulative cultural evolution. Here, we explored the
relationship between imitation and innovation by assessing children's ability to
generate a solution to a novel problem by imitating two different action
sequences demonstrated by two different models, an example of imitation by
combination, which we refer to as "summative imitation." Children (N = 181) from
3 to 5 years of age and across three experiments were tested in a baseline
condition or in one of six demonstration conditions, varying in the number of
models and opening techniques demonstrated. Across experiments, more than 75% of
children evidenced summative imitation, opening both compartments of the problem
box and retrieving the reward hidden in each. Generally, learning different
actions from two different models was as good (and in some cases, better) than
learning from 1 model, but the underlying representations appear to be the same
in both demonstration conditions. These results show that summative imitation not
only facilitates imitation learning but can also result in new solutions to
problems, an essential feature of innovation and cumulative culture.
PMID- 26441781
TI - Measuring anhedonia: impaired ability to pursue, experience, and learn about
reward.
AB - Ribot's (1896) long standing definition of anhedonia as "the inability to
experience pleasure" has been challenged recently following progress in affective
neuroscience. In particular, accumulating evidence suggests that reward consists
of multiple subcomponents of wanting, liking and learning, as initially outlined
by Berridge and Robinson (2003), and these processes have been proposed to relate
to appetitive, consummatory and satiety phases of a pleasure cycle. Building on
this work, we recently proposed to reconceptualize anhedonia as "impairments in
the ability to pursue, experience, and/or learn about pleasure, which is often,
but not always accessible to conscious awareness." (Romer Thomsen et al., 2015).
This framework is in line with Treadway and Zald's (2011) proposal to
differentiate between motivational and consummatory types of anhedonia, and
stresses the need to combine traditional self-report measures with behavioral
measures or procedures. In time, this approach may lead to improved clinical
assessment and treatment. In line with our reconceptualization, increasing
evidence suggests that reward processing deficits are not restricted to impaired
hedonic impact in major psychiatric disorders. Successful translations of animal
models have led to strong evidence of impairments in the ability to pursue and
learn about reward in psychiatric disorders such as major depressive disorder,
schizophrenia, and addiction. It is of high importance that we continue to
systematically target impairments in all phases of reward processing across
disorders using behavioral testing in combination with neuroimaging techniques.
This in turn has implications for diagnosis and treatment, and is essential for
the purposes of identifying the underlying neurobiological mechanisms. Here I
review recent progress in the development and application of behavioral
procedures that measure subcomponents of anhedonia across relevant patient
groups, and discuss methodological caveats as well as implications for assessment
and treatment.
PMID- 26441783
TI - Can money heal all wounds? Social exchange norm modulates the preference for
monetary versus social compensation.
AB - Compensation is a kind of pro-social behavior that can restore a social
relationship jeopardized by interpersonal transgression. The effectiveness of a
certain compensation strategy (e.g., repaying money, sharing loss, etc.) may vary
as a function of the social norm/relationship. Previous studies have shown that
two types of norms (or relationships), monetary/exchange and social/communal,
differentially characterize people's appraisal of and response to social
exchanges. In this study, we investigated how individual differences in
preference for these norms affect individuals' perception of others' as well as
the selection of their own reciprocal behaviors. In a two-phase experiment with
interpersonal transgression, we asked the participant to perform a dot-estimation
task with two partners who occasionally and unintentionally inflicted noise
stimulation upon the participant (first phase). As compensation one partner gave
money to the participant 80% of the time (the monetary partner) and the other
bore the noise for the participant 80% of the time (the social partner). Results
showed that the individuals' preference for compensation (repaying money versus
bearing noise) affected their relationship (exchange versus communal) with the
partners adopting different compensation strategies: participants tended to form
communal relationships and felt closer to the partner whose compensation strategy
matched their own preference. The participants could be differentiated into a
social group, who tended to form communal relationship with the social partner,
and a monetary group, who tended to form communal relationship with the monetary
partner. In the second phase of the experiment, when the participants became
transgressors and were asked to compensate for their transgression with money,
the social group offered more compensation to the social partners than to the
monetary partners, while the monetary group compensated less than the social
group in general and showed no difference in their offers to the monetary and
social partners. These findings demonstrate that the effectiveness of
compensation varies as a function of individuals' preference for communal versus
monetary norm and that monetary compensation alone does not heal all wounds.
PMID- 26441784
TI - Socioeconomic status and oppositional defiant disorder in preschoolers: parenting
practices and executive functioning as mediating variables.
AB - OBJECTIVES: To investigate the mediating mechanisms of oppositional defiant
disorder (ODD) in preschoolers through pathways analysis, considering the family
socioeconomic status (SES) as the independent variable and the parenting style
and the children's executive functioning (EF) as the mediating factors. METHOD:
The sample included 622 three-year-old children from the general population.
Multi-informant reports from parents and teachers were analyzed. RESULTS:
Structural Equation Modeling showed that the associations between SES, EF,
parenting style and ODD levels differed by children's gender: (a) for girls, the
association of low SES and high ODD scores was partially mediated by difficulties
in EF inhibition, and parenting practices defined by corporal punishment and
inconsistent discipline obtained a quasi-significant indirect effect into the
association between SES and ODD; (b) for boys, SES and EF (inhibition and
emotional control) had a direct effect on ODD with no mediation. CONCLUSION: SES
seems a good indicator to identify children at high-risk for prevention and
intervention programs for ODD. Girls with ODD in families of low SES may
particularly benefit from parent training practices and training in inhibition
control.
PMID- 26441785
TI - Corrigendum: A comparative study of exceptional experiences of clients seeking
advice and of subjects in an ordinary population.
AB - [This corrects the article on p. 65 in vol. 4, PMID: 23423775.].
PMID- 26441786
TI - Predicting self-rated mental and physical health: the contributions of subjective
socioeconomic status and personal relative deprivation.
AB - Lower subjective socioeconomic status (SSS) and higher personal relative
deprivation (PRD) relate to poorer health. Both constructs concern people's
perceived relative social position, but they differ in their emphasis on the
reference groups people use to determine their comparative disadvantage (national
population vs. similar others) and the importance of resentment that may arise
from such adverse comparisons. We investigated the relative utility of SSS and
PRD as predictors of self-rated physical and mental health (e.g., self-rated
health, stress, health complaints). Across six studies, self-rated physical and
mental health were on the whole better predicted by measures of PRD than by SSS
while controlling for objective socioeconomic status (SES), with SSS rarely
contributing unique variance over and above PRD and SES. Studies 4-6 discount the
possibility that the superiority of PRD over SSS in predicting health is due to
psychometric differences (e.g., reliability) or response biases between the
measures.
PMID- 26441787
TI - Social coordination in animal vocal interactions. Is there any evidence of turn
taking? The starling as an animal model.
AB - Turn-taking in conversation appears to be a common feature in various human
cultures and this universality raises questions about its biological basis and
evolutionary trajectory. Functional convergence is a widespread phenomenon in
evolution, revealing sometimes striking functional similarities between very
distant species even though the mechanisms involved may be different. Studies on
mammals (including non-human primates) and bird species with different levels of
social coordination reveal that temporal and structural regularities in vocal
interactions may depend on the species' social structure. Here we test the
hypothesis that turn-taking and associated rules of conversations may be an
adaptive response to the requirements of social life, by testing the
applicability of turn-taking rules to an animal model, the European starling.
Birdsong has for many decades been considered as one of the best models of human
language and starling songs have been well described in terms of vocal production
and perception. Starlings do have vocal interactions where alternating patterns
predominate. Observational and experimental data on vocal interactions reveal
that (1) there are indeed clear temporal and structural regularities, (2) the
temporal and structural patterning is influenced by the immediate social context,
the general social situation, the individual history, and the internal state of
the emitter. Comparison of phylogenetically close species of Sturnids reveals
that the alternating pattern of vocal interactions varies greatly according to
the species' social structure, suggesting that interactional regularities may
have evolved together with social systems. These findings lead to solid bases of
discussion on the evolution of communication rules in relation to social
evolution. They will be discussed also in terms of processes, at the light of
recent neurobiological findings.
PMID- 26441788
TI - Emotional processing in Parkinson's disease and schizophrenia: evidence for
response bias deficits in PD.
AB - Deficits in facial emotion recognition in Parkinson's disease (PD) patients has
been well documented. Nevertheless, it is still not clear whether facial emotion
recognition deficits are secondary to other cognitive impairments. The aim of
this study was to answer the question of whether deficits in facial emotion
recognition in PD result from impaired sensory processes, or from impaired
decision processes. To address this question, we tested the ability to recognize
a mixture of basic and complex emotions in 38 non-demented PD patients and 38
healthy controls matched on demographic characteristics. By using a task with an
increased level of ambiguity, in conjunction with the signal detection theory, we
were able to differentiate between sensitivity and response bias in facial
emotion recognition. Sensitivity and response bias for facial emotion recognition
were calculated using a d-prime value and a c index respectively. Our study is
the first to employ the EIS-F scale for assessing facial emotion recognition
among PD patients; to test its validity as an assessment tool, a group comprising
schizophrenia patients and healthy controls were also tested. Patients with PD
recognized emotions with less accuracy than healthy individuals (d-prime) and
used a more liberal response criterion (c index). By contrast, patients with
schizophrenia merely showed diminished sensitivity (d-prime). Our results suggest
that an impaired ability to recognize facial emotions in PD patients may result
from both decreased sensitivity and a significantly more liberal response
criteria, whereas facial emotion recognition in schizophrenia may stem from a
generalized sensory impairment only.
PMID- 26441789
TI - Brain lateralization and self-reported symptoms of ADHD in a population sample of
adults: a dimensional approach.
AB - Many clinical studies reported a compromised brain lateralization in patients
with Attention-Deficit/Hyperactivity Disorder (ADHD) without being conclusive
about whether the deficit existed in the left or right hemisphere. It is well
recognized that studying ADHD dimensionally is more controlled for comorbid
problems and medication effects, and provides more accurate assessment of the
symptoms. Therefore, the present study applied the dimensional approach to test
the relationship between brain lateralization and self-reported ADHD symptoms in
a population sample. Eighty-five right-handed university students filled in the
Conners' Adult ADHD Rating Scales and performed a lateralization reaction time
task. The task consists of two matching conditions: one condition requires
nominal identification for letters tapping left hemisphere specialization (Letter
Name-Identity condition) and the other one requires physical and visuospatial
identification for shapes tapping right hemisphere specialization (Shape Physical
Identity condition). The letters or shapes to be matched are presented in left or
right visual field of a fixation cross. For both task conditions, brain
lateralization was indexed as the difference in mean reaction time between left
and right visual field. Linear regression analyses, controlled for mood symptoms
reported by a depression, anxiety, and stress scale, showed no relationship
between the variables. These findings from a population sample of adults do not
support the dimensionality of lateralized information processing deficit in ADHD
symptomatology. However, group comparison analyses showed that subjects with high
level of inattention symptoms close to or above the clinical cut-off had a
reduced right hemisphere processing in the Shape Physical-Identity condition.
PMID- 26441790
TI - Neural correlates of cognitive aging during the perception of facial age: the
role of relatively distant and local texture information.
AB - Previous event-related potential (ERP) research revealed that older relative to
younger adults show reduced inversion effects in the N170 (with more negative
amplitudes for inverted than upright faces), suggestive of impairments in face
perception. However, as these studies used young to middle-aged faces only, this
finding may reflect preferential processing of own- relative to other-age faces
rather than age-related decline. We conducted an ERP study in which young and
older participants categorized young and old upright or inverted faces by age.
Stimuli were presented either unfiltered or low-pass filtered at 30, 20, or 10
cycles per image (CPI). Response times revealed larger inversion effects, with
slower responses for inverted faces, for young faces in young participants. Older
participants did not show a corresponding effect. ERPs yielded a trend toward
reduced N170 inversion effects in older relative to younger adults independent of
face age. Moreover, larger inversion effects for young relative to old faces were
detected, and filtering resulted in smaller N170 amplitudes. The reduced N170
inversion effect in older adults may reflect age-related changes in neural
correlates of face perception. A smaller N170 inversion effect for old faces may
indicate that facial changes with age hamper early face perception stages.
PMID- 26441791
TI - Linguistic explanation and domain specialization: a case study in bound variable
anaphora.
AB - The core question behind this Frontiers research topic is whether explaining
linguistic phenomena requires appeal to properties of human cognition that are
specialized to language. We argue here that investigating this issue requires
taking linguistic research results seriously, and evaluating these for domain
specificity. We present a particular empirical phenomenon, bound variable
interpretations of pronouns dependent on a quantifier phrase, and argue for a
particular theory of this empirical domain that is couched at a level of
theoretical depth which allows its principles to be evaluated for domain
specialization. We argue that the relevant principles are specialized when they
apply in the domain of language, even if analogs of them are plausibly at work
elsewhere in cognition or the natural world more generally. So certain principles
may be specialized to language, though not, ultimately, unique to it. Such
specialization is underpinned by ultimately biological factors, hence part of UG.
PMID- 26441792
TI - "A letter for Dr. Outgroup": on the effects of an indicator of competence and
chances for altruism toward a member of a stigmatized out-group.
AB - The lost letter technique is an unobtrusive method to investigate attitudes in a
particular population. Ostensibly lost letters from senders who apparently belong
to different groups or addressed to recipients from apparently different groups
are dispersed in public places, and return rates represent a measure of
altruistic or discriminatory behavior toward one group or another. In two field
experiments using the lost letter technique, we investigated the influence of
group membership and the presence or absence of a doctorate degree as an
indicator of competence on the likelihood of receiving helping behavior.
Experiment 1 showed that a generic member of a low-status ethnic out-group (Turks
living in Germany) was the target of discrimination, while a generic member of a
non-stigmatized out-group (French in Germany) was not. Moreover, when the name of
the member from the stigmatized out-group was (vs. was not) preceded by a
doctorate degree, more of the allegedly lost letters were returned. There were no
such differential effects for recipients who were members of the in-group
(Germans) or the non-stigmatized out-group (French). Experiment 2 showed that a
recipient from the stigmatized out-group (Turk) with a doctorate degree received
more letters when the sender was German versus Turkish (i.e., from the
recipient's own group). Overall, the sender's ethnic group membership was an
important factor for the likelihood of receiving an ostensibly lost letter, in
that fewer letters arrived from a sender with a Turkish (vs. German) name. We
conclude that the likelihood of altruistic behavior toward out-group members can
increase when in-group members intend to communicate with competent out-group
members. Therefore, under certain conditions, the presentation of a highly
competent member of an otherwise stigmatized out-group may serve as a
discrimination buffer.
PMID- 26441793
TI - The duality of gaze: eyes extract and signal social information during sustained
cooperative and competitive dyadic gaze.
AB - In contrast to non-human primate eyes, which have a dark sclera surrounding a
dark iris, human eyes have a white sclera that surrounds a dark iris. This high
contrast morphology allows humans to determine quickly and easily where others
are looking and infer what they are attending to. In recent years an enormous
body of work has used photos and schematic images of faces to study these aspects
of social attention, e.g., the selection of the eyes of others and the shift of
attention to where those eyes are directed. However, evolutionary theory holds
that humans did not develop a high contrast morphology simply to use the eyes of
others as attentional cues; rather they sacrificed camouflage for communication,
that is, to signal their thoughts and intentions to others. In the present study
we demonstrate the importance of this by taking as our starting point the
hypothesis that a cornerstone of non-verbal communication is the eye contact
between individuals and the time that it is held. In a single simple study we
show experimentally that the effect of eye contact can be quickly and profoundly
altered merely by having participants, who had never met before, play a game in a
cooperative or competitive manner. After the game participants were asked to make
eye contact for a prolonged period of time (10 min). Those who had played the
game cooperatively found this terribly difficult to do, repeatedly talking and
breaking gaze. In contrast, those who had played the game competitively were able
to stare quietly at each other for a sustained period. Collectively these data
demonstrate that when looking at the eyes of a real person one both acquires and
signals information to the other person. This duality of gaze is critical to non
verbal communication, with the nature of that communication shaped by the
relationship between individuals, e.g., cooperative or competitive.
PMID- 26441794
TI - The linguistic roots of natural pedagogy.
AB - Natural pedagogy is a human-specific capacity that allows us to acquire cultural
information from communication even before the emergence of the first words,
encompassing three core elements: (i) a sensitivity to ostensive signals like eye
contact that indicate to infants that they are being addressed through
communication, (ii) a subsequent referential expectation (satisfied by the use of
declarative gestures) and (iii) a biased interpretation of ostensive-referential
communication as conveying relevant information about the referent's kind (Csibra
and Gergely, 2006, 2009, 2011). Remarkably, the link between natural pedagogy and
another human-specific capacity, namely language, has rarely been investigated in
detail. We here argue that children's production and comprehension of declarative
gestures around 10 months of age are in fact expressions of an evolving faculty
of language. Through both declarative gestures and ostensive signals, infants can
assign the roles of third, second, and first person, building the 'deictic space'
that grounds both natural pedagogy and language use. Secondly, we argue that the
emergence of two kinds of linguistic structures (i.e., proto-determiner phrases
and proto-sentences) in the one-word period sheds light on the different kinds of
information that children can acquire or convey at different stages of
development (namely, generic knowledge about kinds and knowledge about particular
events/actions/state of affairs, respectively). Furthermore, the development of
nominal and temporal reference in speech allows children to cognize information
in terms of spatial and temporal relations. In this way, natural pedagogy
transpires as an inherent aspect of our faculty of language, rather than as an
independent adaptation that pre-dates language in evolution or development
(Csibra and Gergely, 2006). This hypothesis is further testable through
predictions it makes on the different linguistic profiles of toddlers with
developmental disorders.
PMID- 26441795
TI - Neuroenhancement and the strength model of self-control.
AB - Neuroenhancement (NE), the use of substances as a means to enhance performance,
has garnered considerable scientific attention of late. While ethical and
epidemiological publications on the topic accumulate, there is a lack of theory
driven psychological research that aims at understanding psychological drivers of
NE. In this perspective article we argue that self-control strength offers a
promising theory-based approach to further understand and investigate NE
behavior. Using the strength model of self-control, we derive two theory-driven
perspectives on NE-self-control research. First, we propose that individual
differences in state/trait self-control strength differentially affect NE
behavior based on one's individual experience of NE use. Building upon this, we
outline promising research questions that (will) further elucidate our
understanding of NE based on the strength model's propositions. Second, we
discuss evidence indicating that popular NE substances (like Methylphenidate) may
counteract imminent losses of self-control strength. We outline how further
research on NE's effects on the ego-depletion effect may further broaden our
understanding of the strength model of self-control.
PMID- 26441797
TI - Perceptual influence of elementary three-dimensional geometry: (2) fundamental
object parts.
AB - Objects usually consist of parts and the question arises whether there are
perceptual features which allow breaking down an object into its fundamental
parts without any additional (e.g., functional) information. As in the first
paper of this sequence, we focus on the division of our world along convex to
concave surface transitions. Here we are using machine vision to produce convex
segments from 3D-scenes. We assume that a fundamental part is one, which we can
easily name while at the same time there is no natural subdivision possible into
smaller parts. Hence in this experiment we presented the computer vision
generated segments to our participants and asked whether they can identify and
name them. Additionally we control against segmentation reliability and we find a
clear trend that reliable convex segments have a high degree of name-ability. In
addition, we observed that using other image-segmentation methods will not yield
nameable entities. This indicates that convex-concave surface transition may
indeed form the basis for dividing objects into meaningful entities. It appears
that other or further subdivisions do not carry such a strong semantical link to
our everyday language as there are no names for them.
PMID- 26441796
TI - Theory-of-mind in individuals with Alstrom syndrome is related to executive
functions, and verbal ability.
AB - OBJECTIVE: This study focuses on cognitive prerequisites for the development of
theory-of-mind (ToM), the ability to impute mental states to self and others in
young adults with Alstrom syndrome (AS). AS is a rare and quite recently
described recessively inherited ciliopathic disorder which causes progressive
sensorineural hearing loss and juvenile blindness, as well as many other organ
dysfunctions. Two cognitive abilities were considered; Phonological working
memory (WM) and executive functions (EF), both of importance in speech
development. METHODS: Ten individuals (18-37 years) diagnosed with AS, and 20
individuals with no known impairment matched for age, gender, and educational
level participated. Sensory functions were measured. Information about motor
functions and communicative skills was obtained from responses to a
questionnaire. ToM was assessed using Happes strange stories, verbal ability by a
vocabulary test, phonological WM by means of an auditory presented non-word
serial recall task and EF by tests of updating and inhibition. RESULTS: The AS
group performed at a significantly lower level than the control group in both the
ToM task and the EF tasks. A significant correlation was observed between recall
of non-words and EF in the AS group. Updating, but not inhibition, correlated
significantly with verbal ability, whereas both updating and inhibition were
significantly related to the ability to initiate and sustain communication.
Poorer performance in the ToM and EF tasks were related to language perseverance
and motor mannerisms. CONCLUSION: The AS group displayed a delayed ToM as well as
reduced phonological WM, EF, and verbal ability. A significant association
between ToM and EF, suggests a compensatory role of EF. This association may
reflect the importance of EF to perceive and process input from the social
environment when the social interaction is challenged by dual sensory loss. We
argue that limitations in EF capacity in individuals with AS, to some extent, may
be related to early blindness and progressive hearing loss, but maybe also to
gene specific abnormalities.
PMID- 26441798
TI - Commentary: Unlearning implicit social biases during sleep.
PMID- 26441799
TI - The simultaneous perception of auditory-tactile stimuli in voluntary movement.
AB - The simultaneous perception of multimodal information in the environment during
voluntary movement is very important for effective reactions to the environment.
Previous studies have found that voluntary movement affects the simultaneous
perception of auditory and tactile stimuli. However, the results of these
experiments are not completely consistent, and the differences may be
attributable to methodological differences in the previous studies. In this
study, we investigated the effect of voluntary movement on the simultaneous
perception of auditory and tactile stimuli using a temporal order judgment task
with voluntary movement, involuntary movement, and no movement. To eliminate the
potential effect of stimulus predictability and the effect of spatial information
associated with large-scale movement in the previous studies, we randomized the
interval between the start of movement and the first stimulus, and used small
scale movement. As a result, the point of subjective simultaneity (PSS) during
voluntary movement shifted from the tactile stimulus being first during
involuntary movement or no movement to the auditory stimulus being first. The
just noticeable difference (JND), an indicator of temporal resolution, did not
differ across the three conditions. These results indicate that voluntary
movement itself affects the PSS in auditory-tactile simultaneous perception, but
it does not influence the JND. In the discussion of these results, we suggest
that simultaneous perception may be affected by the efference copy.
PMID- 26441800
TI - The eye-voice span during reading aloud.
AB - Although eye movements during reading are modulated by cognitive processing
demands, they also reflect visual sampling of the input, and possibly preparation
of output for speech or the inner voice. By simultaneously recording eye
movements and the voice during reading aloud, we obtained an output measure that
constrains the length of time spent on cognitive processing. Here we investigate
the dynamics of the eye-voice span (EVS), the distance between eye and voice. We
show that the EVS is regulated immediately during fixation of a word by either
increasing fixation duration or programming a regressive eye movement against the
reading direction. EVS size at the beginning of a fixation was positively
correlated with the likelihood of regressions and refixations. Regression
probability was further increased if the EVS was still large at the end of a
fixation: if adjustment of fixation duration did not sufficiently reduce the EVS
during a fixation, then a regression rather than a refixation followed with high
probability. We further show that the EVS can help understand cognitive
influences on fixation duration during reading: in mixed model analyses, the EVS
was a stronger predictor of fixation durations than either word frequency or word
length. The EVS modulated the influence of several other predictors on single
fixation durations (SFDs). For example, word-N frequency effects were larger with
a large EVS, especially when word N-1 frequency was low. Finally, a comparison of
SFDs during oral and silent reading showed that reading is governed by similar
principles in both reading modes, although EVS maintenance and articulatory
processing also cause some differences. In summary, the EVS is regulated by
adjusting fixation duration and/or by programming a regressive eye movement when
the EVS gets too large. Overall, the EVS appears to be directly related to
updating of the working memory buffer during reading.
PMID- 26441801
TI - Adoptive parenting and attachment: association of the internal working models
between adoptive mothers and their late-adopted children during adolescence.
AB - INTRODUCTION: Recent literature has shown that the good outcome of adoption would
mostly depend on the quality of adoptive parenting, which is strongly associated
with the security of parental internal working models (IWMs) of attachment.
Specifically, attachment states-of-mind of adoptive mothers classified as free
and autonomous and without lack of resolution of loss or trauma could represent a
good protective factor for adopted children, previously maltreated and neglected.
While most research on adoptive families focused on pre-school and school-aged
children, the aim of this study was to assess the concordance of IWMs of
attachment in adoptive dyads during adolescence. METHOD: Our pilot-study involved
76 participants: 30 adoptive mothers (mean age = 51.5 +/- 4.3), and their 46 late
adopted adolescents (mean age = 13.9 +/- 1.6), who were all aged 4-9 years old at
time of adoption (mean age = 6.3 +/- 1.5). Attachment representations of adopted
adolescents were assessed by the Friend and Family Interview (FFI), while
adoptive mothers' state-of-mind with respect to attachment was classified by the
Adult Attachment Interview (AAI). Adolescents' verbal intelligence was controlled
for. RESULTS: Late-adopted adolescents were classified as follows: 67% secure,
26% dismissing, and 7% preoccupied in the FFI, while their adoptive mothers' AAI
classifications were 70% free-autonomous, 7% dismissing, and 23% unresolved. We
found a significant concordance of 70% (32 dyads) between the secure-insecure FFI
and AAI classifications. Specifically adoptive mothers with high coherence of
transcript and low unresolved loss tend to have late-adopted children with high
secure attachment, even if the adolescents' verbal intelligence made a
significant contribution to this prediction. DISCUSSION: Our results provides an
empirical contribution to the literature concerning the concordance of attachment
in adoptive dyads, highlighting the beneficial impact of highly coherent states
of-mind of adoptive mothers on the attachment representations of their late
adopted adolescent children.
PMID- 26441802
TI - Why language really is not a communication system: a cognitive view of language
evolution.
AB - While most evolutionary scenarios for language see it as a communication system
with consequences on the language-ready brain, there are major difficulties for
such a view. First, language has a core combination of features-semanticity,
discrete infinity, and decoupling-that makes it unique among communication
systems and that raise deep problems for the view that it evolved for
communication. Second, extant models of communication systems-the code model of
communication (Millikan, 2005) and the ostensive model of communication (Scott
Phillips, 2015) cannot account for language evolution. I propose an alternative
view, according to which language first evolved as a cognitive tool, following
Fodor's (1975, 2008) Language of Thought Hypothesis, and was then exapted
(externalized) for communication. On this view, a language-ready brain is a brain
profoundly reorganized in terms of connectivity, allowing the human conceptual
system to emerge, triggering the emergence of syntax. Language as used in
communication inherited its core combination of features from the Language of
Thought.
PMID- 26441803
TI - Learning from history: the need for a synthetic approach to human cognition.
PMID- 26441804
TI - Happiness in texting times.
AB - Assessing national levels of happiness has become an important research and
policy issue in recent years. We examined happiness and satisfaction in Ireland
using phone text messaging to collect large-scale longitudinal data from 3,093
members of the general Irish population. For six consecutive weeks, participants'
happiness and satisfaction levels were assessed. For four consecutive weeks
(weeks 2-5) a different random third of the sample got feedback on the previous
week's mean happiness and satisfaction ratings. Text messaging proved a feasible
means of assessing happiness and satisfaction, with almost three quarters (73%)
of participants completing all assessments. Those who received feedback on the
previous week's mean ratings were eight times more likely to complete the
subsequent assessments than those not receiving feedback. Providing such feedback
data on mean levels of happiness and satisfaction did not systematically bias
subsequent ratings either toward or away from these normative anchors. Texting is
a simple and effective means to collect population level happiness and
satisfaction data.
PMID- 26441805
TI - Warm-hearted businessmen, competitive housewives? Effects of gender-fair language
on adolescents' perceptions of occupations.
AB - Recent studies from countries with grammatical gender languages (e.g., French)
found both children and adults to more frequently think of female jobholders and
to consider women's success in male dominated occupations more likely when the
jobs were described in pair forms (i.e., by explicit reference to male and female
jobholders, e.g., inventeuses et inventeurs; French feminine and masculine plural
forms for inventors), rather than masculine only forms (e.g., inventors). To gain
a better understanding of this phenomenon, we systematically varied the gender
connotation of occupations (males overrepresented, females overrepresented, equal
share of males and females) and measured additional dependent variables,
predicting that gender fair language would reduce the impact of the gender
connotation on participants' perceptions. In a sample of 222 adolescents (aged 12
17) from French speaking Switzerland, we found that pair forms attenuated the
difference in the ascription of success to male and female jobholders in gendered
occupations and attenuated the differential ascription of warmth to prototypical
jobholders in male vs. female dominated jobs. However, no effect of language form
on the ascription of competence was found. These findings suggest that language
policies are an effective tool to impact gendered perceptions, however, they also
hint at competence-related gender stereotypes being in decline.
PMID- 26441806
TI - Using item response theory to investigate the structure of anticipated affect: do
self-reports about future affective reactions conform to typical or maximal
models?
AB - In the present research, we used item response theory (IRT) to examine whether
effective predictions (anticipated affect) conforms to a typical (i.e., what
people usually do) or a maximal behavior process (i.e., what people can do). The
former, correspond to non-monotonic ideal point IRT models, whereas the latter
correspond to monotonic dominance IRT models. A convenience, cross-sectional
student sample (N = 1624) was used. Participants were asked to report on
anticipated positive and negative affect around a hypothetical event (emotions
surrounding the start of a new business). We carried out analysis comparing
graded response model (GRM), a dominance IRT model, against generalized graded
unfolding model, an unfolding IRT model. We found that the GRM provided a better
fit to the data. Findings suggest that the self-report responses to anticipated
affect conform to dominance response process (i.e., maximal behavior). The paper
also discusses implications for a growing literature on anticipated affect.
PMID- 26441807
TI - Watch the target! Effects in the affective misattribution procedure become weaker
(but not eliminated) when participants are motivated to provide accurate
responses to the target.
AB - Previous research showed that priming effects in the affective misattribution
procedure (AMP) are unaffected by direct warnings to avoid an influence of the
primes. The present research examined whether a priming influence is diminished
by task procedures that encourage accurate judgments of the targets. Participants
were motivated to categorize the affective meaning of nonsense targets accurately
by being made to believe that a true word was presented in each trial and by
providing feedback on (allegedly) incorrect responses. This condition produced
robust priming effects. Priming was however reduced and less reliable relative to
more typical AMP conditions in which participants guessed the meaning of openly
presented nonsense targets. Affective judgments of nonsense targets were not
affected by advance knowledge of the response mapping during the priming phase,
which argues against a response-priming explanation of AMP effects. These
findings show that affective primes influence evaluative judgments even in
conditions in which the motivation to provide accurate responses is high and a
priming of motor responses is not possible. Priming effects were however weaker
with high accuracy motivation, suggesting that a focus on accurate judgments is
an effective strategy to control for an unwanted priming influence in the AMP.
PMID- 26441808
TI - Antecedents of maternal parenting stress: the role of attachment style, prenatal
attachment, and dyadic adjustment in first-time mothers.
AB - The transition to parenthood is widely considered a period of increased
vulnerability often accompanied by stress. Abidin conceived parenting stress as
referring to specific difficulties in adjusting to the parenting role. Most
studies of psychological distress arising from the demands of parenting have
investigated the impact of stress on the development of dysfunctional parent
child relationships and on adult and child psychopathology. Studies have largely
focused on mothers' postnatal experience; less attention has been devoted to
maternal prenatal characteristics associated with subsequent parental stress and
studies of maternal prenatal predictors are few. Furthermore, no studies have
examined that association exclusively with samples of first-time mothers. With an
observational prospective study design with two time periods, the aim of this
study was to investigate the role of mothers' attachment style, maternal prenatal
attachment to the fetus and dyadic adjustment during pregnancy (7th months of
gestation) and their potential unique contribution to parenting stress 3 months
after childbirth in a sample of nulliparous women. Results showed significant
correlations between antenatal measures. Maternal attachment style (especially
relationship anxiety) was negatively correlated with prenatal attachment and with
dyadic adjustment; positive correlations resulted between prenatal attachment and
dyadic adjustment. Each of the investigated variables was also good predictor of
parenting stress 3 months after childbirth. Findings suggested how these
dimensions could be considered as risk factors in the transition to motherhood
and in the very beginning of the emergence of the caregiving system, especially
with first-time mothers.
PMID- 26441809
TI - Measuring strategic control in implicit learning: how and why?
AB - Several methods have been developed for measuring the extent to which implicitly
learned knowledge can be applied in a strategic, flexible manner. Examples
include generation exclusion tasks in Serial Reaction Time (SRT) learning
(Goschke, 1998; Destrebecqz and Cleeremans, 2001) and 2-grammar classification
tasks in Artificial Grammar Learning (AGL; Dienes et al., 1995; Norman et al.,
2011). Strategic control has traditionally been used as a criterion for
determining whether acquired knowledge is conscious or unconscious, or which
properties of knowledge are consciously available. In this paper I first
summarize existing methods that have been developed for measuring strategic
control in the SRT and AGL tasks. I then address some methodological and
theoretical questions. Methodological questions concern choice of task, whether
the measurement reflects inhibitory control or task switching, and whether or not
strategic control should be measured on a trial-by-trial basis. Theoretical
questions concern the rationale for including measurement of strategic control,
what form of knowledge is strategically controlled, and how strategic control can
be combined with subjective awareness measures.
PMID- 26441810
TI - How should we measure chunks? a continuing issue in chunking research and a way
forward.
PMID- 26441811
TI - Influence of adult attachment insecurities on parenting self-esteem: the
mediating role of dyadic adjustment.
AB - BACKGROUND: Parenting self-esteem includes two global components, parents' self
efficacy and satisfaction with their parental role, and has a crucial role in
parent-child interactions. The purpose of this study was to develop an
integrative model linking adult attachment insecurities, dyadic adjustment, and
parenting self-esteem. METHODS: The study involved 118 pairs (236 subjects) of
heterosexual parents of a firstborn child aged 0-6 years. They were administered
the Experiences in Close Relationships-Revised (ECR-R) questionnaire, the Dyadic
Adjustment Scale, and the Parenting Sense of Competence Scale. RESULTS: Path
analysis was used to design and test a theoretical integrative model, achieving a
good fit with the data. Findings showed that dyadic adjustment mediates the
negative influence on parenting self-efficacy of both attachment anxiety and
attachment avoidance. Parenting satisfaction is positively influenced by
parenting self-efficacy and negatively affected by child's age. Attachment
anxiety negatively influences parenting satisfaction. CONCLUSION: Our findings
are in line with the theoretical expectations and have promising implications for
future research and intervention programs designed to improve parenting self
esteem.
PMID- 26441812
TI - Historical roots of histrionic personality disorder.
AB - Histrionic Personality Disorder is one of the most ambiguous diagnostic
categories in psychiatry. Hysteria is a classical term that includes a wide
variety of psychopathological states. Ancient Egyptians and Greeks blamed a
displaced womb, for many women's afflictions. Several researchers from the 18th
and 19th centuries studied this theme, namely, Charcot who defined hysteria as a
"neurosis" with an organic basis and Sigmund Freud who redefined "neurosis" as a
re-experience of past psychological trauma. Histrionic personality disorder (HPD)
made its first official appearance in the Diagnostic and Statistical Manual of
Mental Disorders II (DSM-II) and since the DSM-III, HPD is the only disorder that
kept the term derived from the old concept of hysteria. The subject of hysteria
has reflected positions about health, religion and relationships between the
sexes in the last 4000 years, and the discussion is likely to continue.
PMID- 26441813
TI - Skin to skin interactions. Does the infant massage improve the couple
functioning?
AB - Transition to parenthood is a critical stage of life due to several changes the
couple has to handle. A large body of studies described how transition to
parenthood can be linked to the onset of depressive symptoms, as well as the
perception of a low social support, and an increased stress, representing a risk
for the early mother-baby relationship. Infant massage (IM) emerged as a helpful
tool to improve maternal skills in interacting with the baby, and leading toward
a decreasing of post-partum symptoms. However, a growing body of literature
highlights that men also may experience post-partum diseases, representing an
additional risk for the development of the baby. To date, no study observed the
impact of the IM on both partners. The aim of the current qualitative research is
to observe the impact of the IM on a single couple of parents at childbirth. Pre
(Time 1) and post-intervention (Time 3) procedure has been established to observe
the changes occurring over the time in the couple. In particular, each member of
the couple filled out the EPDS, the BDI-II, the MSPSS, and the PSI-SF both at
Time 1 and at Time 3. The treatment (Time 2) was represented by the IM training,
and lasted 4 weeks. Findings revealed a decrease in depressive symptoms in both
partners, as well as an improvement of their perception of stress related to
parental role. No changes has been detected with respect to the perception of
social support. The IM seems to be a helpful approach to prevent the
establishment of pathological conditions in new parents. Although no direct
measures on the child were used, the current qualitative data seem to suggest
that the IM may represent a valuable tool to prevent the onset of early negative
outcomes of the baby. Further investigations and empirical data are needed to
improve the knowledge in this field.
PMID- 26441814
TI - Attentional bias in competitive situations: winner does not take all.
AB - Compared to previous studies of competition with participants' direct
involvement, the current study for the first time investigated the influence of
competitive outcomes on attentional bias from a perspective of an onlooker. Two
simple games were employed: the Rock-Paper-Scissors game (Experiment 1) in which
the outcome is based on luck, and Arm-wrestling (Experiment 2), in which the
outcome is based on the competitors' strength. After observing one of these
games, participants were asked to judge a stimulus presented on either the
winner's or loser's side of a screen. Both experiments yielded the same results,
indicating that the onlookers made much quicker judgments on stimuli presented on
the loser's side than the winner's side. This suggests the existence of an
attention bias for loser-related information once a competition has ended. Our
findings provide a new lens through which the influence of competition results on
human cognitive processing can be understood.
PMID- 26441815
TI - Frequency-dependent changes in the amplitude of low-frequency fluctuations in
internet gaming disorder.
AB - Neuroimaging studies have revealed that the task-related functional brain
activities are impaired in internet gaming disorder (IGD) subjects. However,
little is known about the alternations in spontaneous brain activities about
them. Recent studies have proposed that the brain activities of different
frequency ranges are generated by different nervous activities and have different
physiological and psychological functions. Thus, in this study, we set to explore
the spontaneous brain activities in IGD subjects by measuring the fractional
amplitude of low-frequency fluctuation (fALFF), to investigate band-specific
changes of resting-state fALFF. We subdivided the frequency range into five bands
based on literatures. Comparing to healthy controls, the IGD group showed
decreased fALFF values in the cerebellum posterior lobe and increased fALFF
values in superior temporal gyrus. Significant interactions between frequency
bands and groups were found in the cerebellum, the anterior cingulate, the
lingual gyrus, the middle temporal gyrus, and the middle frontal gyrus. Those
brain regions are proved related to the executive function and decision-making.
These results revealed the changed spontaneous brain activity of IGD, which
contributed to understanding the underlying pathophysiology of IGD.
PMID- 26441816
TI - Functional MRI Preprocessing in Lesioned Brains: Manual Versus Automated Region
of Interest Analysis.
AB - Functional magnetic resonance imaging (fMRI) has significant potential in the
study and treatment of neurological disorders and stroke. Region of interest
(ROI) analysis in such studies allows for testing of strong a priori clinical
hypotheses with improved statistical power. A commonly used automated approach to
ROI analysis is to spatially normalize each participant's structural brain image
to a template brain image and define ROIs using an atlas. However, in studies of
individuals with structural brain lesions, such as stroke, the gold standard
approach may be to manually hand-draw ROIs on each participant's non-normalized
structural brain image. Automated approaches to ROI analysis are faster and more
standardized, yet are susceptible to preprocessing error (e.g., normalization
error) that can be greater in lesioned brains. The manual approach to ROI
analysis has high demand for time and expertise, but may provide a more accurate
estimate of brain response. In this study, commonly used automated and manual
approaches to ROI analysis were directly compared by reanalyzing data from a
previously published hypothesis-driven cognitive fMRI study, involving
individuals with stroke. The ROI evaluated is the pars opercularis of the
inferior frontal gyrus. Significant differences were identified in task-related
effect size and percent-activated voxels in this ROI between the automated and
manual approaches to ROI analysis. Task interactions, however, were consistent
across ROI analysis approaches. These findings support the use of automated
approaches to ROI analysis in studies of lesioned brains, provided they employ a
task interaction design.
PMID- 26441817
TI - A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for
Central Nervous System Targets.
AB - Hundreds of millions of U.S. dollars are invested in the research and development
of a single drug. Lead compound development is an area ripe for new design
strategies. Therapeutic lead candidates have been traditionally found using high
throughput in vitro pharmacological screening, a costly method for assaying
thousands of compounds. This approach has recently been augmented by virtual
screening (VS), which employs computer models of the target protein to narrow the
search for possible leads. A variant of VS is fragment-based drug design (FBDD),
an emerging in silico lead discovery method that introduces low-molecular weight
fragments, rather than intact compounds, into the binding pocket of the receptor
model. These fragments serve as starting points for "growing" the lead candidate.
Current efforts in virtual FBDD within central nervous system (CNS) targets are
reviewed, as is a recent rule-based optimization strategy in which new molecules
are generated within a 3D receptor-binding pocket using the fragment as a
scaffold. This process not only places special emphasis on creating synthesizable
molecules but also exposes computational questions worth addressing. Fragment
based methods provide a viable, relatively low-cost alternative for therapeutic
lead discovery and optimization that can be applied to CNS targets to augment
current design strategies.
PMID- 26441818
TI - Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy - Where to
from Here?
AB - Hypoxia-ischemia before or around the time of birth occurs in approximately
2/1000 live births and is associated with a high risk of death or lifelong
disability. Therapeutic hypothermia is now well established as standard treatment
for infants with moderate to severe hypoxic-ischemic encephalopathy but is only
partially effective. There is compelling preclinical and clinical evidence that
hypothermia is most protective when it is started as early as possible after
hypoxia-ischemia. Further improvements in outcome from therapeutic hypothermia
are very likely to arise from strategies to reduce the delay before starting
treatment of affected infants. In this review, we examine evidence that current
protocols are reasonably close to the optimal depth and duration of cooling, but
that the optimal rate of rewarming after hypothermia is unclear. The potential
for combination treatments to augment hypothermic neuroprotection has
considerable promise, particularly with endogenous targets such as melatonin and
erythropoietin, and noble gases such as xenon. We dissect the critical importance
of preclinical studies using realistic delays in treatment and clinically
relevant cooling protocols when examining combination treatment, and that for
many strategies overlapping mechanisms of action can substantially attenuate any
effects.
PMID- 26441820
TI - End of OSLER Test Sessions in Parkinson's Disease do not Correspond to True Sleep
Onset: Results from an Exploratory Study.
AB - The aim of the present study was to evaluate the correlation between the end of
an Oxford sleep resistance (OSLER) test session and a neurophysiological marker
of sleep onset in Parkinson's disease (PD) patients. Single center study was
conducted in PD patients with excessive daytime sleepiness [Epworth sleepiness
scale (ESS) >9]. The OSLER test was conducted with a concomitant
electroencephalography (EEG), electromyography (mentalis), right and left
electroculogram, and video monitoring. Neurophysiological (NP) sleep onset was
defined according to AASM criteria (2005). Five PD patients with mean ESS of 14
(10-16) were included. OSLER test duration was shorter than 40 min in all
patients (mean duration 20 min and 39 s). No patient fulfilled neurophysiological
criteria to sleep onset at the time of OSLER test termination. In 13 OSLER
sessions that ended before 40 min, eight had microsleeps in the last 30 s before
the end of the test. NP monitoring showed signs of sleepiness in all patients. In
PD patients, the early termination of an OSLER test session may not correspond to
NP criteria of sleep onset. However, in all PD patients with abnormal OSLER
results, there were EEG signs of sleepiness, which do not exclude the potential
utility of OSLER test to evaluate the risk of falling asleep.
PMID- 26441819
TI - Pushing the Limits: Chronotype and Time of Day Modulate Working Memory-Dependent
Cerebral Activity.
AB - Morning-type individuals experience more difficulties to maintain optimal
attentional performance throughout a normal waking day than evening types.
However, time-of-day modulations may differ across cognitive domains. Using
functional magnetic resonance imaging (fMRI), we investigated how chronotype and
time of day interact with working memory at different levels of cognitive
load/complexity in a N-back paradigm (N0-, N2-, and N3-back levels). Extreme
morning- and evening-type individuals underwent two fMRI sessions during N-back
performance, one 1.5 h (morning) and one 10.5 h (evening) after wake-up time
scheduled according to their habitual sleep-wake preference. At the behavioral
level, increasing working memory load resulted in lower accuracy while chronotype
and time of day only exerted a marginal impact on performance. Analyses of
neuroimaging data disclosed an interaction between chronotype, time of day, and
the modulation of cerebral activity by working memory load in the thalamus and in
the middle frontal cortex. In the subjective evening hours, evening types
exhibited higher thalamic activity than morning types at the highest working
memory load condition only (N3-back). Conversely, morning-type individuals
exhibited higher activity than evening-type participants in the middle frontal
gyrus during the morning session in the N3-back condition. Our data emphasize
interindividual differences in time-of-day preferences and underlying cerebral
activity, which should be taken into account when investigating vigilance state
effects in task-related brain activity. These results support the hypothesis that
higher task complexity leads to a chronotype-dependent increase in thalamic and
frontal brain activity, permitting stabilization of working memory performance
across the day.
PMID- 26441821
TI - Reconciling Magnetically Induced Vertigo and Nystagmus.
PMID- 26441822
TI - New Cerebral Microbleeds and Mechanism of Post-Thrombolysis Remote Intracerebral
Hemorrhage: "Red Meets White" Revisited.
PMID- 26441823
TI - Protein Citrullination: A Proposed Mechanism for Pathology in Traumatic Brain
Injury.
AB - Protein citrullination is a calcium-driven post-translational modification
proposed to play a causative role in the neurodegenerative disorders of
Alzheimer's disease, multiple sclerosis (MS), and prion disease. Citrullination
can result in the formation of antigenic epitopes that underlie pathogenic
autoimmune responses. This phenomenon, which is best understood in rheumatoid
arthritis, may play a role in the chronic dysfunction following traumatic brain
injury (TBI). Despite substantial evidence of aberrations in calcium signaling
following TBI, there is little understanding of how TBI alters citrullination in
the brain. The present investigation addressed this gap by examining the effects
of TBI on the distribution of protein citrullination and on the specific cell
types involved. Immunofluorescence revealed that controlled cortical impact in
rats profoundly up--regulated protein citrullination in the cerebral cortex,
external capsule, and hippocampus. This response was exclusively seen in
astrocytes; no such effects were observed on the status of protein citrullination
in neurons, oligodendrocytes or microglia. Further, proteomic analyses
demonstrated that the effects of TBI on citrullination were confined to a
relatively small subset of neural proteins. Proteins most notably affected were
those also reported to be citrullinated in other disorders, including prion
disease and MS. In vivo findings were extended in an in vitro model of simulated
TBI employing normal human astrocytes. Pharmacologically induced calcium
excitotoxicity was shown to activate the citrullination and breakdown of glial
fibrillary acidic protein, producing a novel candidate TBI biomarker and
potential target for autoimmune recognition. In summary, these findings
demonstrate that the effects of TBI on protein citrullination are selective with
respect to brain region, cell type, and proteins modified, and may contribute to
a role for autoimmune dysfunction in chronic pathology following TBI.
PMID- 26441824
TI - The Effects of Aging on Clinical Vestibular Evaluations.
AB - Balance disorders are common issues for aging populations due to the effects of
normal aging on peripheral vestibular structures. These changes affect the
results of vestibular function evaluations and make the interpretation of these
results more difficult. The objective of this article is to review the current
state of knowledge of clinically relevant vestibular measures. We will first
focus on otolith function assessment methods cervical-VEMP (cVEMP) and ocular
VEMP (oVEMP), then the caloric and video-head impulse test (vHIT) methods for
semicircular canals assessment. cVEMP and oVEMP are useful methods, though
research on the effects of age for some parameters are still inconclusive. vHIT
results are largely independent of age as compared to caloric stimulation and
should therefore be preferred for the evaluation of the semicircular canals
function.
PMID- 26441825
TI - Anti-Abeta Autoantibodies in Amyloid Related Imaging Abnormalities (ARIA):
Candidate Biomarker for Immunotherapy in Alzheimer's Disease and Cerebral Amyloid
Angiopathy.
AB - Amyloid-related imaging abnormalities (ARIA) represent the major severe side
effect of amyloid-beta (Abeta) immunotherapy for Alzheimer's disease (AD). Early
biomarkers of ARIA represent an important challenge to ensure safe and beneficial
effects of immunotherapies, given that different promising clinical trials in
prodromal and subjects at risk for AD are underway. The recent demonstration that
cerebrospinal fluid (CSF) anti-Abeta autoantibodies play a key role in the
development of the ARIA-like events characterizing cerebral amyloid angiopathy
related inflammation generated great interest in the field of immunotherapy.
Herein, we critically review the growing body of evidence supporting the
monitoring of CSF anti-Abeta autoantibody as a promising candidate biomarker for
ARIA in clinical trials.
PMID- 26441827
TI - In a Class of Their Own - RXFP1 and RXFP2 are Unique Members of the LGR Family.
AB - The leucine-rich repeat-containing G protein-coupled receptors (LGRs) family
consists of three groups: types A, B, and C and all contain a large extracellular
domain (ECD) made up of the structural motif - the leucine-rich repeat (LRR). In
the LGRs, the ECD binds the hormone or ligand, usually through the LRRs, that
ultimately results in activation and signaling. Structures are available for the
ECD of type A and B LGRs, but not the type C LGRs. This review discusses the
structural features of LRR proteins, and describes the known structures of the
type A and B LGRs and predictions that can be made for the type C LGRs. The
mechanism of activation of the LGRs is discussed with a focus on the role of the
low-density lipoprotein class A (LDLa) module, a unique feature of the type C
LGRs. While the LDLa module is essential for activation of the type C LGRs, the
molecular mechanism for this process is unknown. Experimental data for the
potential interactions of the type C LGR ligands with the LRR domain, the
transmembrane domain, and the LDLa module are summarized.
PMID- 26441828
TI - Early Life Stress Induced by Limited Nesting Material Produces Metabolic
Resilience in Response to a High-Fat and High-Sugar Diet in Male Rats.
AB - Environmental conditions experienced in early life can profoundly influence long
term metabolic health, but the additive impact of poor nutrition is poorly
understood. Here, we tested the hypothesis that early life stress (ELS) induced
by limited nesting material (LN) combined with high-fat and high-sugar diet
(HFHS) post-weaning would worsen diet-related metabolic risk. Sprague-Dawley male
rats were exposed to LN, postnatal days 2-9, and at weaning (3 weeks), siblings
were given unlimited access to chow or HFHS resulting in (Con-Chow, Con-HFHS, LN
Chow, and LN-HFHS, n = 11-15/group). Glucose and insulin tolerance were tested
and rats were killed at 13 weeks. LN rats weighed less at weaning but were not
different to control at 13 weeks; HFHS diet led to similar increases in body
weight. LN-chow rats had improved glucose and insulin tolerance relative to Con
Chow, whereas LN-HFHS improved insulin sensitivity versus Con-HFHS, associated
with increased peroxisome proliferator-activated receptor gamma co-activator-1
alpha (Pgc-1alpha) mRNA in muscle. No effect of LN on plasma or liver
triglycerides was observed, and hepatic gluconeogenic regulatory genes were
unaltered. In summary, this study demonstrates that ELS induced by LN conferred
some metabolic protection against insulin and/or glucose intolerance in a diet
dependent manner during adulthood.
PMID- 26441829
TI - Effects of a Macro-Nutrient Preload on Type 2 Diabetic Patients.
AB - AIMS: Macro-nutrient preloads given 30 min before regular meals may improve
metabolism. The aim was to investigate how type 2 diabetic patients react to a
preload consisting of a blend of macro-nutrients with a low-glycemic index
(Inzone Preload((r))). METHODS: In a before-after study design, 30 subjects with
type 2 diabetes mellitus (T2DM) were enrolled in a 12-week program. All subjects
were given Inzone Preload (43% proteins, 29% carbohydrates, 10% lipids, and 9%
fibers, 71 kcal), 30 min before each meal during 12 weeks. Fasting glucose and
postprandial 2 h glucose were monitored every second week. Body weight (BW) and
waist circumference were measured each month. Fasting plasma glucose,
glycosylated hemoglobin, serum lipids, fasting insulin, C-reactive protein, and
homeostasis model assessment were evaluated before and after the intervention.
Subjective appetite was monitored using visual analogue scales after the Inzone
Preload. RESULTS: The dietary intervention significantly influenced several
metabolic parameters compared to base line. Inzone Preload treatment reduced mean
postprandial plasma glucose levels (12.2 +/- 1.2 vs. 10.5 +/- 2.0 mmol/L), HbA1c
(7.4 +/- 0.3 vs. 7.1 +/- 0.2%), mean total cholesterol (4.8 +/- 0.9 vs. 4.3 +/-
0.8 mmol/L), low-density lipoprotein cholesterol (2.8 +/- 0.6 vs. 2.5 +/- 0.4
mmol/L), and CRP (1.5 +/- 1.4 vs. 0.7 +/- 0.7 mg/L). BW loss of more than 3% was
seen in 13 participants (43%). Feelings of satiety were significantly higher
after Inzone Preload than after habitual breakfast (p < 0.05). No significant
changes in fasting blood glucose, high-density lipoprotein and total
triacylglycerol, HOMA-IR, and HOMA-beta were observed. CONCLUSION: A macro
nutrient preload treatment reduces postprandial glucose, inflammatory markers,
and serum lipids in patients with T2DM. Approximately half of the study group
also displayed reduced BW.
PMID- 26441826
TI - Diabetes and Hepatitis C: A Two-Way Association.
AB - Diabetes and hepatitis C infection are both prevalent diseases worldwide, and are
associated with increased morbidity and mortality. Most studies, but not all,
have shown that patients with chronic hepatitis C are more prone to develop type
2 diabetes (T2D) compared to healthy controls, as well as when compared to
patients with other liver diseases, including hepatitis B. Furthermore,
epidemiological studies have revealed that patients with T2D may also be at
higher risk for worse outcomes of their hepatitis C infection, including reduced
rate of sustained virological response, progression to fibrosis and cirrhosis,
and higher risk for development of hepatocellular carcinoma. Moreover, hepatitis
C infection and mainly its treatment, interferon alpha, can trigger the
development of type 1 diabetes. In this review, we discuss the existing data on
this two-way association between diabetes and hepatitis C infection with emphasis
on possible mechanisms. It remains to be determined whether the new curative
therapies for chronic hepatitis C will improve outcomes in diabetic hepatitis C
patients, and conversely whether treatment with Metformin will reduce
complications from hepatitis C virus infection. We propose an algorithm for
diabetes screening and follow-up in hepatitis C patients.
PMID- 26441830
TI - Differences in Signal Activation by LH and hCG are Mediated by the LH/CG
Receptor's Extracellular Hinge Region.
AB - The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be
activated by binding two slightly different gonadotropic glycoprotein hormones,
choriogonadotropin (CG) - secreted by the placenta, and lutropin (LH) - produced
by the pituitary. They induce different signaling profiles at the LHCGR. This
cannot be explained by binding to the receptor's leucine-rich-repeat domain
(LRRD), as this binding is similar for the two hormones. We therefore speculate
that there are previously unknown differences in the hormone/receptor interaction
at the extracellular hinge region, which might help to understand functional
differences between the two hormones. We have therefore performed a detailed
study of the binding and action of LH and CG at the LHCGR hinge region. We
focused on a primate-specific additional exon in the hinge region, which is
located between LRRD and the serpentine domain. The segment of the hinge region
encoded by exon10 was previously reported to be only relevant to hLH signaling,
as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged
hCG signaling. We designed an advanced homology model of the hormone/LHCGR
complex, followed by experimental characterization of relevant fragments in the
hinge region. In addition, we examined predictions of a helical exon10-encoded
conformation by block-wise polyalanine (helix supporting) mutations. These helix
preserving modifications showed no effect on hormone-induced signaling. However,
introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P
within the exon10-helix has, in contrast to exon10-deletion, no impact on hLH,
but only on hCG signaling. This opposite effect on signaling by hLH and hCG can
be explained by distinct sites of hormone interaction in the hinge region. In
conclusion, our analysis provides details of the differences between hLH- and hCG
induced signaling that are mainly determined in the L2-beta loop of the hormones
and in the hinge region of the receptor.
PMID- 26441831
TI - Pituitary Adenoma and the Chemokine Network: A Systemic View.
PMID- 26441832
TI - Discovery and Development of Small Molecule Allosteric Modulators of Glycoprotein
Hormone Receptors.
AB - Glycoprotein hormones, follicle-stimulating hormone (FSH), luteinizing hormone
(LH), and thyroid-stimulating hormone (TSH) are heterodimeric proteins with a
common alpha-subunit and hormone-specific beta-subunit. These hormones are
dominant regulators of reproduction and metabolic processes. Receptors for the
glycoprotein hormones belong to the family of G protein-coupled receptors. FSH
receptor (FSHR) and LH receptor are primarily expressed in somatic cells in ovary
and testis to promote egg and sperm production in women and men, respectively.
TSH receptor is expressed in thyroid cells and regulates the secretion of T3 and
T4. Glycoprotein hormones bind to the large extracellular domain of the receptor
and cause a conformational change in the receptor that leads to activation of
more than one intracellular signaling pathway. Several small molecules have been
described to activate/inhibit glycoprotein hormone receptors through allosteric
sites of the receptor. Small molecule allosteric modulators have the potential to
be administered orally to patients, thus improving the convenience of treatment.
It has been a challenge to develop a small molecule allosteric agonist for
glycoprotein hormones that can mimic the agonistic effects of the large natural
ligand to activate similar signaling pathways. However, in the past few years,
there have been several promising reports describing distinct chemical series
with improved potency in preclinical models. In parallel, proposal of new
structural model for FSHR and in silico docking studies of small molecule ligands
to glycoprotein hormone receptors provide a giant leap on the understanding of
the mechanism of action of the natural ligands and new chemical entities on the
receptors. This review will focus on the current status of small molecule
allosteric modulators of glycoprotein hormone receptors, their effects on common
signaling pathways in cells, their utility for clinical application as
demonstrated in preclinical models, and use of these molecules as novel tools to
dissect the molecular signaling pathways of these receptors.
PMID- 26441835
TI - Editorial: Podocyte Pathology and Nephropathy.
PMID- 26441834
TI - Novel Regulator of Acylated Ghrelin, CF801, Reduces Weight Gain, Rebound Feeding
after a Fast, and Adiposity in Mice.
AB - Ghrelin is a 28 amino acid hormonal peptide that is intimately related to the
regulation of food intake and body weight. Once secreted, ghrelin binds to the
growth hormone secretagogue receptor-1a, the only known receptor for ghrelin and
is capable of activating a number of signaling cascades, ultimately resulting in
an increase in food intake and adiposity. Because ghrelin has been linked to
overeating and the development of obesity, a number of pharmacological
interventions have been generated in order to interfere with either the
activation of ghrelin or interrupting ghrelin signaling as a means to reducing
appetite and decrease weight gain. Here, we present a novel peptide, CF801,
capable of reducing circulating acylated ghrelin levels and subsequent body
weight gain and adiposity. To this end, we show that IP administration of CF801
is sufficient to reduce circulating plasma acylated ghrelin levels. Acutely,
intraperitoneal injections of CF801 resulted in decreased rebound feeding after
an overnight fast. When delivered chronically, they decreased weight gain and
adiposity without affecting caloric intake. CF801, however, did cause a change in
diet preference, decreasing preference for a high-fat diet and increasing
preference for regular chow diet. Given the complexity of ghrelin receptor
function, we propose that CF801, along with other compounds that regulate ghrelin
secretion, may prove to be a beneficial tool in the study of the ghrelin system,
and potential targets for ghrelin-based obesity treatments without altering the
function of ghrelin receptors.
PMID- 26441833
TI - Plasticity of the Melanocortin System: Determinants and Possible Consequences on
Food Intake.
AB - The melanocortin system is one of the most important neuronal pathways involved
in the regulation of food intake and is probably the best characterized. Agouti
related peptide (AgRP) and proopiomelanocortin (POMC) expressing neurons located
in the arcuate nucleus of the hypothalamus are the key elements of this system.
These two neuronal populations are sensitive to circulating molecules and receive
many excitatory and inhibitory inputs from various brain areas. According to
sensory and metabolic information they integrate, these neurons control different
aspects of feeding behavior and orchestrate autonomic responses aimed at
maintaining energy homeostasis. Interestingly, composition and abundance of pre
synaptic inputs onto arcuate AgRP and POMC neurons vary in the adult hypothalamus
in response to changes in the metabolic state, a phenomenon that can be
recapitulated by treatment with hormones, such as leptin or ghrelin. As described
in other neuroendrocrine systems, glia might be determinant to shift the synaptic
configuration of AgRP and POMC neurons. Here, we discuss the physiological
outcome of the synaptic plasticity of the melanocortin system, and more
particularly its contribution to the control of energy balance. The discovery of
this attribute has changed how we view obesity and related disorders, and opens
new perspectives for their management.
PMID- 26441836
TI - Editorial: Cell-Based Therapies for Diabetic Microvascular Complications.
PMID- 26441837
TI - Research Perspectives on the Regulation and Physiological Functions of FGF21 and
its Association with NAFLD.
AB - Fibroblast growth factor 21 (FGF21) is a metabolic hormone primarily secreted
from the liver and functions in multiple tissues. Various transcription factors
induce FGF21 expression in the liver, which indicates that FGF21 is a mediator of
multiple environmental cues. FGF21 alters metabolism under starvation conditions,
protects the body from energy depletion, and extends life span. Pharmacological
administration of FGF21 alleviates dyslipidemia and induces weight loss in obese
animals. In addition to the well-studied functions of FG21, several lines of
recent evidence indicate a possible link between FGF21 and non-alcoholic fatty
liver disease (NAFLD). High serum levels of FGF21 are associated with NAFLD and
its risk factors, such as endoplasmic reticulum stress and chronic inflammation.
In addition, FGF21 alleviates the major risk factors of NAFLD, including obesity,
dyslipidemia, and insulin insensitivity. Thus, FGF21 is a potential drug
candidate for diseases, such as NAFLD, dyslipidemia, and type 2 diabetes. In this
review, the research perspectives of FGF21 and therapeutic potencies of FGF21 as
a modulator of NAFLD are summarized.
PMID- 26441838
TI - Metabolic Effects of FGF-21: Thermoregulation and Beyond.
AB - Fibroblast growth factor (FGF)-21, a member of the FGF family, is a novel hormone
involved in the control of metabolism by modulating glucose homeostasis, insulin
sensitivity, ketogenesis, and promoting adipose tissue "browning." Recent studies
demonstrated that brown adipose tissue is not only a target for FGF-21, but is
also a potentially important source of systemic FGF-21. These findings support
the hypothesis that FGF-21 plays a physiologic role in thermogenesis and
thermogenic recruitment of white adipose tissue by an autocrine-paracrine axis.
This review examines the role of FGF-21 in thermogenesis from the perspective of
cell-based, animal model, and human studies. We also present recent advances in
the characterization of FGF-21's regulation of metabolism.
PMID- 26441840
TI - Regulation and Function of RFRP-3 (GnIH) Neurons during Postnatal Development.
AB - RFamide-related peptide-3 (RFRP-3) [mammalian ortholog to gonadotropin-inhibiting
hormone (GnIH)] potently inhibits gonadotropin secretion in mammals. Studies of
RFRP-3 immunoreactivity and Rfrp expression (the gene encoding RFRP-3) in
mammalian brains have uncovered several possible pathways regulating RFRP-3
neurons, shedding light on their potential role in reproduction and other
processes, and pharmacological studies have probed the target sites of RFRP-3
action. Despite this, there is currently no major consensus on RFRP-3's specific
endogenous role(s) in reproductive physiology. Here, we discuss the latest
evidence relating to RFRP-3 neuron regulation and function during development and
sexual maturation, focusing on rodents. We highlight significant changes in RFRP
3 and Rfrp expression, as well as RFRP-3 neuronal activation, during key stages
of postnatal and pubertal development and also discuss recent evidence testing
the requisite role of RFRP-3 receptors for normal pubertal timing and
developmental LH secretion. Interestingly, some findings suggest that endogenous
RFRP-3 signaling may not be necessary for the puberty timing, at least in some
species, forcing new hypotheses to be generated regarding this peptide's
functional significance to sexual maturation and development.
PMID- 26441839
TI - Neuronal Control of Adaptive Thermogenesis.
AB - The obesity epidemic continues rising as a global health challenge, despite the
increasing public awareness and the use of lifestyle and medical interventions.
The biomedical community is urged to develop new treatments to obesity. Excess
energy is stored as fat in white adipose tissue (WAT), dysfunction of which lies
at the core of obesity and associated metabolic disorders. By contrast, brown
adipose tissue (BAT) burns fat and dissipates chemical energy as heat. The
development and activation of "brown-like" adipocytes, also known as beige cells,
result in WAT browning and thermogenesis. The recent discovery of brown and beige
adipocytes in adult humans has sparked the exploration of the development,
regulation, and function of these thermogenic adipocytes. The central nervous
system drives the sympathetic nerve activity in BAT and WAT to control heat
production and energy homeostasis. This review provides an overview of the
integration of thermal, hormonal, and nutritional information on hypothalamic
circuits in thermoregulation.
PMID- 26441841
TI - Fgf8-Deficient Mice Compensate for Reduced GnRH Neuronal Population and Exhibit
Normal Testicular Function.
AB - Gonadotropin-releasing hormone (GnRH) is critical for the onset and maintenance
of reproduction in vertebrates. The development of GnRH neurons is highly
dependent on fibroblast growth factor (Fgf) signaling. Mice with a hypomorphic
Fgf8 allele (Fgf8 Het) exhibited a ~50% reduction in GnRH neuron number at birth.
Female Fgf8 Het mice were fertile but showed significantly delayed puberty.
However, it was unclear if these mice suffered additional loss of GnRH neurons
after birth, and if male Fgf8 Het mice had normal pubertal transition and
testicular function. In this study, we examined postnatal GnRH neuron number and
hypothalamic GnRH content in Fgf8 Het mice from birth to 120 days of age.
Further, we examined seminal vesicle and testicular growth, testicular histology,
and circulating luteinizing hormone (LH) around and after pubertal transition.
Our results showed that GnRH neuron numbers were significantly and consistently
reduced in Fgf8 Het mice of both sexes in all ages examined, suggesting these
animals were born with an inherently defective GnRH system, and no further
postnatal loss of GnRH neurons had occurred. Despite an innately compromised GnRH
system, male and female Fgf8 mice exhibited normal levels of immunoassayable
hypothalamic GnRH peptide at all ages examined except on 60 days of age,
suggesting increased GnRH synthesis or reduced turnover as a compensatory
mechanism. Fgf8 Het males also had normal seminal vesicle and testicular
mass/body mass ratios, testicular histology, and circulating LH. Overall, our
data speak to the extraordinary ability of a GnRH system permanently compromised
by developmental defect to overcome pre-existing deficiencies to ensure pubertal
progression and reproduction.
PMID- 26441842
TI - Mineralocorticoid Receptors in the Pathophysiology of Vascular Inflammation and
Atherosclerosis.
AB - Atherosclerosis is a chronic inflammatory disease of the vasculature that causes
significant morbidity and mortality from myocardial infarction, stroke, and
peripheral vascular disease. Landmark clinical trials revealed that
mineralocorticoid receptor (MR) antagonists improve outcomes in cardiovascular
patients. Conversely, enhanced MR activation by the hormone aldosterone is
associated with increased risk of MI, stroke, and cardiovascular death. This
review summarizes recent advances in our understanding of the role of aldosterone
and the MR in the pathogenesis of vascular inflammation and atherosclerosis as it
proceeds from risk factor-induced endothelial dysfunction and inflammation to
plaque formation, progression, and ultimately rupture with thrombosis, the cause
of acute ischemia. The role of the MR in converting cardiac risk factors into
endothelial dysfunction, in enhancing leukocyte adhesion and infiltration into
the vasculature, in promoting systemic inflammation and vascular oxidative
stress, and in plaque destabilization and thrombosis are discussed. A greater
understanding of the mechanisms by which the MR promotes atherosclerosis has
substantial potential to identify novel treatment targets to improve
cardiovascular health and decrease mortality.
PMID- 26441843
TI - Paracoccidioides spp. ferrous and ferric iron assimilation pathways.
AB - Iron is an essential micronutrient for almost all organisms, including fungi.
Usually, fungi can uptake iron through receptor-mediated internalization of a
siderophore or heme, and/or reductive iron assimilation (RIA). Traditionally, the
RIA pathway consists of ferric reductases (Fres), ferroxidase (Fet3) and a high
affinity iron permease (Ftr1). Paracoccidioides spp. genomes do not present an
Ftr1 homolog. However, this fungus expresses zinc regulated transporter homologs
(Zrts), members of the ZIP family of membrane transporters that are able in some
organisms to transport zinc and iron. A 2,3,5-triphenyltetrazolium chloride (TTC)
overlay assay indicates that both Pb01 and Pb18 express a ferric reductase
activity; however, (59)Fe uptake assays indicate that only in Pb18 is this
activity coupled to a reductase-dependent iron uptake pathway. In addition, Zrts
are up-regulated in iron deprivation, as indicated by RNAseq and qRT-PCR using
Pb01 transcripts. RNAseq strategy also demonstrated that transcripts related to
siderophore uptake and biosynthesis are up-regulated in iron-deprived condition.
The data suggest that the fungus could use both a non-classical RIA, comprising
ferric reductases and Fe/Zn permeases (Zrts), and siderophore uptake pathways
under iron-limited conditions. The study of iron metabolism reveals novel surface
molecules that could function as accessible targets for drugs to block iron
uptake and, consequently, inhibit pathogen's proliferation.
PMID- 26441844
TI - Deep subsurface mine stalactites trap endemic fissure fluid Archaea, Bacteria,
and Nematoda possibly originating from ancient seas.
AB - Stalactites (CaCO3 and salt) from water seeps are frequently encountered in
ceilings of mine tunnels whenever they intersect water-bearing faults or
fractures. To determine whether stalactites could be mineralized traps for
indigenous fracture water microorganisms, we analyzed stalactites collected from
three different mines ranging in depth from 1.3 to 3.1 km. During sampling in
Beatrix gold mine (1.4 km beneath the surface), central South Africa, CaCO3
stalactites growing on the mine tunnel ceiling were collected and observed, in
two cases, to contain a living obligate brackish water/marine nematode species,
Monhystrella parvella. After sterilization of the outer surface, mineral layers
were physically removed from the outside to the interior, and DNA extracted.
Based upon 16S and 18S rRNA gene sequencing, Archaea, Bacteria, and Eukarya in
different combinations were detected for each layer. Using CT scan and electron
microscopy the inner structure of CaCO3 and salt stalactites were analyzed. CaCO3
stalactites show a complex pattern of lamellae carrying bacterially precipitated
mineral structures. Nematoda were clearly identified between these layers
confirming that bacteria and nematodes live inside the stalactites and not only
in the central straw. Salt stalactites exhibit a more uniform internal structure.
Surprisingly, several Bacteria showing highest sequence identities to marine
species were identified. This, together with the observation that the nematode M.
parvella recovered from Beatrix gold mine stalactite can only survive in a salty
environment makes the origin of the deep subsurface colonization enigmatic. The
possibility of a Permian origin of fracture fluids is discussed. Our results
indicate stalactites are suitable for biodiversity recovery and act as natural
traps for microorganisms in the fissure water long after the water that formed
the stalactite stopped flowing.
PMID- 26441845
TI - Biopolymers from lactic acid bacteria. Novel applications in foods and beverages.
AB - Lactic acid bacteria (LAB) are microorganisms widely used in the fermented food
industry worldwide. Certain LAB are able to produce exopolysaccharides (EPS)
either attached to the cell wall (capsular EPS) or released to the extracellular
environment (EPS). According to their composition, LAB may synthesize
heteropolysaccharides or homopolysaccharides. A wide diversity of EPS are
produced by LAB concerning their monomer composition, molecular mass, and
structure. Although EPS-producing LAB strains have been traditionally applied in
the manufacture of dairy products such as fermented milks and yogurts, their use
in the elaboration of low-fat cheeses, diverse type of sourdough breads, and
certain beverages are some of the novel applications of these polymers. This work
aims to collect the most relevant issues of the former reviews concerning the
monomer composition, structure, and yields and biosynthetic enzymes of EPS from
LAB; to describe the recently characterized EPS and to present the application of
both EPS-producing strains and their polymers in the fermented (specifically
beverages and cereal-based) food industry.
PMID- 26441847
TI - Fe biomineralization mirrors individual metabolic activity in a nitrate-dependent
Fe(II)-oxidizer.
AB - Microbial biomineralization sometimes leads to periplasmic encrustation, which is
predicted to enhance microorganism preservation in the fossil record. Mineral
precipitation within the periplasm is, however, thought to induce death, as a
result of permeability loss preventing nutrient and waste transit across the cell
wall. This hypothesis had, however, never been investigated down to the single
cell level. Here, we cultured the nitrate reducing Fe(II) oxidizing bacteria
Acidovorax sp. strain BoFeN1 that have been previously shown to promote the
precipitation of a diversity of Fe minerals (lepidocrocite, goethite, Fe
phosphate) encrusting the periplasm. We investigated the connection of Fe
biomineralization with carbon assimilation at the single cell level, using a
combination of electron microscopy and Nano-Secondary Ion Mass Spectrometry. Our
analyses revealed strong individual heterogeneities of Fe biomineralization.
Noteworthy, a small proportion of cells remaining free of any precipitate
persisted even at advanced stages of biomineralization. Using pulse chase
experiments with (13)C-acetate, we provide evidence of individual phenotypic
heterogeneities of carbon assimilation, correlated with the level of Fe
biomineralization. Whereas non- and moderately encrusted cells were able to
assimilate acetate, higher levels of periplasmic encrustation prevented any
carbon incorporation. Carbon assimilation only depended on the level of Fe
encrustation and not on the nature of Fe minerals precipitated in the cell wall.
Carbon assimilation decreased exponentially with increasing cell-associated Fe
content. Persistence of a small proportion of non-mineralized and metabolically
active cells might constitute a survival strategy in highly ferruginous
environments. Eventually, our results suggest that periplasmic Fe
biomineralization may provide a signature of individual metabolic status, which
could be looked for in the fossil record and in modern environmental samples.
PMID- 26441846
TI - Microbiomes: unifying animal and plant systems through the lens of community
ecology theory.
AB - The field of microbiome research is arguably one of the fastest growing in
biology. Bacteria feature prominently in studies on animal health, but fungi
appear to be the more prominent functional symbionts for plants. Despite the
similarities in the ecological organization and evolutionary importance of animal
bacterial and plant-fungal microbiomes, there is a general failure across
disciplines to integrate the advances made in each system. Researchers studying
bacterial symbionts in animals benefit from greater access to efficient
sequencing pipelines and taxonomic reference databases, perhaps due to high
medical and veterinary interest. However, researchers studying plant-fungal
symbionts benefit from the relative tractability of fungi under laboratory
conditions and ease of cultivation. Thus each system has strengths to offer, but
both suffer from the lack of a common conceptual framework. We argue that
community ecology best illuminates complex species interactions across space and
time. In this synthesis we compare and contrast the animal-bacterial and plant
fungal microbiomes using six core theories in community ecology (i.e.,
succession, community assembly, metacommunities, multi-trophic interactions,
disturbance, restoration). The examples and questions raised are meant to spark
discussion amongst biologists and lead to the integration of these two systems,
as well as more informative, manipulatory experiments on microbiomes research.
PMID- 26441848
TI - Versatile transformations of hydrocarbons in anaerobic bacteria: substrate ranges
and regio- and stereo-chemistry of activation reactions.
AB - Anaerobic metabolism of hydrocarbons proceeds either via addition to fumarate or
by hydroxylation in various microorganisms, e.g., sulfate-reducing or
denitrifying bacteria, which are specialized in utilizing n-alkanes or
alkylbenzenes as growth substrates. General pathways for carbon assimilation and
energy gain have been elucidated for a limited number of possible substrates. In
this work the metabolic activity of 11 bacterial strains during anaerobic growth
with crude oil was investigated and compared with the metabolite patterns
appearing during anaerobic growth with more than 40 different hydrocarbons
supplied as binary mixtures. We show that the range of co-metabolically formed
alkyl- and arylalkyl-succinates is much broader in n-alkane than in alkylbenzene
utilizers. The structures and stereochemistry of these products are resolved.
Furthermore, we demonstrate that anaerobic hydroxylation of alkylbenzenes does
not only occur in denitrifiers but also in sulfate reducers. We propose that
these processes play a role in detoxification under conditions of solvent stress.
The thermophilic sulfate-reducing strain TD3 is shown to produce n
alkylsuccinates, which are suggested not to derive from terminal activation of n
alkanes, but rather to represent intermediates of a metabolic pathway short
cutting fumarate regeneration by reverse action of succinate synthase. The
outcomes of this study provide a basis for geochemically tracing such processes
in natural habitats and contribute to an improved understanding of microbial
activity in hydrocarbon-rich anoxic environments.
PMID- 26441849
TI - Staphylococcus aureus strains associated with food poisoning outbreaks in France:
comparison of different molecular typing methods, including MLVA.
AB - Staphylococcal food poisoning outbreaks (SFPOs) are frequently reported in
France. However, most of them remain unconfirmed, highlighting a need for a
better characterization of isolated strains. Here we analyzed the genetic
diversity of 112 Staphylococcus aureus strains isolated from 76 distinct SFPOs
that occurred in France over the last 30 years. We used a recently developed
multiple-locus variable-number tandem-repeat analysis (MLVA) protocol and
compared this method with pulsed field gel electrophoresis (PFGE), spa-typing and
carriage of genes (se genes) coding for 11 staphylococcal enterotoxins (i.e.,
SEA, SEB, SEC, SED, SEE, SEG, SEH, SEI, SEJ, SEP, SER). The strains known to have
an epidemiological association with one another had identical MLVA types, PFGE
profiles, spa-types or se gene carriage. MLVA, PFGE and spa-typing divided 103
epidemiologically unrelated strains into 84, 80, and 50 types respectively
demonstrating the high genetic diversity of S. aureus strains involved in SFPOs.
Each MLVA type shared by more than one strain corresponded to a single spa-type
except for one MLVA type represented by four strains that showed two different
but closely related-spa-types. The 87 enterotoxigenic strains were distributed
across 68 distinct MLVA types that correlated all with se gene carriage except
for four MLVA types. The most frequent se gene detected was sea, followed by seg
and sei and the most frequently associated se genes were sea-seh and sea-sed-sej
ser. The discriminatory ability of MLVA was similar to that of PFGE and higher
than that of spa-typing. This MLVA protocol was found to be compatible with high
throughput analysis, and was also faster and less labor-intensive than PFGE. MLVA
holds promise as a suitable method for investigating SFPOs and tracking the
source of contamination in food processing facilities in real time.
PMID- 26441850
TI - HIV-1 Tat and cocaine mediated synaptopathy in cortical and midbrain neurons is
prevented by the isoflavone Equol.
AB - Illicit drugs, such as cocaine, are known to increase the likelihood and severity
of HIV-1 associated neurocognitive disorders (HAND). In the current studies
synaptic integrity was assessed following exposure to low concentrations of the
HIV-1 viral protein Tat 1-86B, with or without cocaine, by quantifying
filamentous actin (F-actin) rich structures (i.e., puncta and dendritic spines)
on neuronal dendrites in vitro. In addition, the synapse-protective effects of
either R-Equol (RE) or S-Equol (SE; derivatives of the soy isoflavone, daidzein)
were determined. Individually, neither low concentrations of HIV-1 Tat (10 nM)
nor low concentrations of cocaine (1.6 MUM) had any significant effect on F-actin
puncta number; however, the same low concentrations of HIV-1 Tat + cocaine in
combination significantly reduced dendritic synapses. This synaptic reduction was
prevented by pre-treatment with either RE or SE, in an estrogen receptor beta
dependent manner. In sum, targeted therapeutic intervention with SE may prevent
HIV-1 + drug abuse synaptopathy, and thereby potentially influence the
development of HAND.
PMID- 26441851
TI - Phenotypic changes in the brain of SIV-infected macaques exposed to
methamphetamine parallel macrophage activation patterns induced by the common
gamma-chain cytokine system.
AB - One factor in the development of neuroAIDS is the increase in the migration of
pro-inflammatory CD8 T cells across the blood-brain barrier. Typically these
cells are involved with keeping the viral load down. However, the persistence of
above average numbers of CD8 T cells in the brain, not necessarily specific to
viral peptides, is facilitated by the upregulation of IL15 from astrocytes, in
the absence of IL2, in the brain environment. Both IL15 and IL2 are common gamma
chain (gammac) cytokines. Here, using the non-human primate model of neuroAIDS,
we have demonstrated that exposure to methamphetamine, a powerful illicit drug
that has been associated with HIV exposure and neuroAIDS severity, can cause an
increase in molecules of the gammac system. Among these molecules, IL15, which is
upregulated in astrocytes by methamphetamine, and that induces the proliferation
of T cells, may also be involved in driving an inflammatory phenotype in innate
immune cells of the brain. Therefore, methamphetamine and IL15 may be critical in
the development and aggravation of central nervous system immune-mediated
inflammatory pathology in HIV-infected drug abusers.
PMID- 26441853
TI - Filamentous fungi from extreme environments as a promising source of novel
bioactive secondary metabolites.
AB - Natural product search is undergoing resurgence upon the discovery of a huge
previously unknown potential for secondary metabolite (SM) production hidden in
microbial genomes. This is also the case for filamentous fungi, since their
genomes contain a high number of "orphan" SM gene clusters. Recent estimates
indicate that only 5% of existing fungal species have been described, thus the
potential for the discovery of novel metabolites in fungi is huge. In this
context, fungi thriving in harsh environments are of particular interest since
they are outstanding producers of unusual chemical structures. At present, there
are around 16 genomes from extreme environment-isolated fungi in databases. In a
preliminary analysis of three of these genomes we found that several of the
predicted SM gene clusters are probably involved in the biosynthesis of compounds
not yet described. Genome mining strategies allow the exploitation of the
information in genome sequences for the discovery of new natural compounds. The
synergy between genome mining strategies and the expected abundance of SMs in
fungi from extreme environments is a promising path to discover new natural
compounds as a source of medically useful drugs.
PMID- 26441852
TI - Bacterial diversity and successional patterns during biofilm formation on freshly
exposed basalt surfaces at diffuse-flow deep-sea vents.
AB - Many deep-sea hydrothermal vent systems are regularly impacted by volcanic
eruptions, leaving fresh basalt where abundant animal and microbial communities
once thrived. After an eruption, microbial biofilms are often the first visible
evidence of biotic re-colonization. The present study is the first to investigate
microbial colonization of newly exposed basalt surfaces in the context of vent
fluid chemistry over an extended period of time (4-293 days) by deploying basalt
blocks within an established diffuse-flow vent at the 9 degrees 50' N vent field
on the East Pacific Rise. Additionally, samples obtained after a recent eruption
at the same vent field allowed for comparison between experimental results and
those from natural microbial re-colonization. Over 9 months, the community
changed from being composed almost exclusively of Epsilonproteobacteria to a more
diverse assemblage, corresponding with a potential expansion of metabolic
capabilities. The process of biofilm formation appears to generate similar
surface-associated communities within and across sites by selecting for a subset
of fluid-associated microbes, via species sorting. Furthermore, the high
incidence of shared operational taxonomic units over time and across different
vent sites suggests that the microbial communities colonizing new surfaces at
diffuse-flow vent sites might follow a predictable successional pattern.
PMID- 26441854
TI - Carbon fixation by basalt-hosted microbial communities.
AB - Oceanic crust is a massive potential habitat for microbial life on Earth, yet our
understanding of this ecosystem is limited due to difficulty in access. In
particular, measurements of rates of microbial activity are sparse. We used
stable carbon isotope incubations of crustal samples, coupled with functional
gene analyses, to examine the potential for carbon fixation on oceanic crust.
Both seafloor-exposed and subseafloor basalts were recovered from different mid
ocean ridge and hot spot environments (i.e., the Juan de Fuca Ridge, the Mid
Atlantic Ridge, and the Loihi Seamount) and incubated with (13)C-labeled
bicarbonate. Seafloor-exposed basalts revealed incorporation of (13)C-label into
organic matter over time, though the degree of incorporation was heterogeneous.
The incorporation of (13)C into biomass was inconclusive in subseafloor basalts.
Translating these measurements into potential rates of carbon fixation indicated
that 0.1-10 nmol C g(-1) rock d(-1) could be fixed by seafloor-exposed rocks.
When scaled to the global production of oceanic crust, this suggests carbon
fixation rates of 10(9)-10(12) g C year(-1), which matches earlier predictions
based on thermodynamic calculations. Functional gene analyses indicate that the
Calvin cycle is likely the dominant biochemical mechanism for carbon fixation in
basalt-hosted biofilms, although the reductive acetyl-CoA pathway and reverse TCA
cycle likely play some role in net carbon fixation. These results provide
empirical evidence for autotrophy in oceanic crust, suggesting that basalt-hosted
autotrophy could be a significant contributor of organic matter in this remote
and vast environment.
PMID- 26441856
TI - Magnesium ions mitigate biofilm formation of Bacillus species via downregulation
of matrix genes expression.
AB - The objective of this study was to investigate the effect of Mg(2+) ions on
biofilm formation by Bacillus species, which are considered as problematic
microorganisms in the food industry. We found that magnesium ions are capable to
inhibit significantly biofilm formation of Bacillus species at 50 mM
concentration and higher. We further report that Mg(2+) ions don't inhibit
bacterial growth at elevated concentrations; hence, the mode of action of Mg(2+)
ions is apparently specific to inhibition of biofilm formation. Biofilm formation
depends on the synthesis of extracellular matrix, whose production in Bacillus
subtilis is specified by two major operons: the epsA-O and tapA operons. We
analyzed the effect of Mg(2+) ions on matrix gene expression using
transcriptional fusions of the promoters for eps and tapA to the gene encoding
beta galactosidase. The expression of the two matrix operons was reduced
drastically in response to Mg(2+) ions suggesting about their inhibitory effect
on expression of the matrix genes in B. subtilis. Since the matrix gene
expression is tightly controlled by Spo0A dependent pathway, we conclude that
Mg(2+) ions could affect the signal transduction for biofilm formation through
this pathway.
PMID- 26441855
TI - Chassis optimization as a cornerstone for the application of synthetic biology
based strategies in microbial secondary metabolism.
AB - The increased number of bacterial genome sequencing projects has generated over
the last years a large reservoir of genomic information. In silico analysis of
this genomic data has renewed the interest in bacterial bioprospecting for
bioactive compounds by unveiling novel biosynthetic gene clusters of unknown or
uncharacterized metabolites. However, only a small fraction of those metabolites
is produced under laboratory-controlled conditions; the remaining clusters
represent a pool of novel metabolites that are waiting to be "awaken". Activation
of the biosynthetic gene clusters that present reduced or no expression (known as
cryptic or silent clusters) by heterologous expression has emerged as a strategy
for the identification and production of novel bioactive molecules. Synthetic
biology, with engineering principles at its core, provides an excellent framework
for the development of efficient heterologous systems for the expression of
biosynthetic gene clusters. However, a common problem in its application is the
host-interference problem, i.e., the unpredictable interactions between the
device and the host that can hamper the desired output. Although an effort has
been made to develop orthogonal devices, the most proficient way to overcome the
host-interference problem is through genome simplification. In this review we
present an overview on the strategies and tools used in the development of
hosts/chassis for the heterologous expression of specialized metabolites
biosynthetic gene clusters. Finally, we introduce the concept of specialized host
as the next step of development of expression hosts.
PMID- 26441857
TI - Functional analysis of the sporulation-specific diadenylate cyclase CdaS in
Bacillus thuringiensis.
AB - Cyclic di-AMP (c-di-AMP) is a recently discovered bacterial secondary messenger
molecule, which is associated with various physiological functions. In the genus
Bacillus, the intracellular level and turnover of c-di-AMP are mainly regulated
by three diadenylate cyclases (DACs), including DisA, CdaA and CdaS, and two c-di
AMP-specific phosphodiesterases (GdpP and PgpH). In this study, we demonstrated
that CdaS protein from B. thuringiensis is a hexameric DAC protein that can
convert ATP or ADP to c-di-AMP in vitro and the N-terminal YojJ domain is
essential for the DAC activity. Based on the markerless gene knock-out method, we
demonstrated that the transcription of cdaS was initiated by the sporulation
specific sigma factor sigma(H) and the deletion of cdaS significantly delayed
sporulation and parasporal crystal formation. These findings contrast with
similar experiments conducted using B. subtilis, wherein transcription of its
cdaS was initiated by the sigma factor sigma(G). Deletion of all the three DAC
genes from a single strain was unsuccessful, suggesting that c-di-AMP is an
indispensable molecule in B. thuringiensis. Phylogenetic analysis indicated
increased diversity of CdaS in the B. cereus and B. subtilis Bacillus subgroups.
In summary, this study identifies important aspects in the regulation of c-di-AMP
in the genus Bacillus.
PMID- 26441858
TI - Manipulation of oil synthesis in Nannochloropsis strain NIES-2145 with a
phosphorus starvation-inducible promoter from Chlamydomonas reinhardtii.
AB - Microalgae accumulate triacylglycerols (TAGs) under conditions of nutrient
stress. Phosphorus (P) starvation induces the accumulation of TAGs, and the cells
under P starvation maintain growth through photosynthesis. We recently reported
that P starvation-dependent overexpression of type-2 diacylglycerol acyl-CoA
acyltransferase (CrDGTT4) from Chlamydomonas reinhardtii using a
sulfoquinovosyldiacylglycerol synthase 2 (SQD2) promoter, which has increased
activity during P starvation, enhances TAG accumulation in C. reinhardtii cells.
As a result, the content of C18:1 fatty acid, a preferred substrate of CrDGTT4,
is increased in TAGs. Here we isolated genes encoding SQD2 from strain NIES-2145
of the eustigmatophyte Nannochloropsis and showed that their expression, like
that in C. reinhardtii, was up-regulated during P starvation. To enhance oil
accumulation under P starvation, we transformed pCrSQD2-CrDGTT4 into
Nannochloropsis strain NIES-2145. The transformants had a fatty acid composition
that was more similar to that of C. reinhardtii, which resulted in enhanced TAG
accumulation and higher 18:1(9) content. The results indicated that the P
starvation-inducible promoter of C. reinhardtii was able to drive expression of
the CrDGTT4 gene in Nannochloropsis strain NIES-2145 under P starvation. We
conclude that the heterologous CrSQD2 promoter is effective in manipulating TAG
synthesis in Nannochloropsis during P starvation.
PMID- 26441859
TI - Characterization of antibiotic resistance in commensal bacteria from an
aquaculture ecosystem.
AB - The objective of the study was to improve the understanding of antibiotic
resistance (AR) ecology through characterization of antibiotic-resistant
commensal isolates associated with an aquaculture production system. A total of
4767 isolates non-susceptible to sulfamethoxazole/trimethoprim (Sul/Tri),
tetracycline (Tet), erythromycin (Erm), or cefotaxime (Ctx), originated from
fish, feed, and environmental samples of an aquaculture farm with no known
history of antibiotic applications were examined. Close to 80% of the isolates
exhibited multi-drug resistance in media containing the corresponding
antibiotics, and representative AR genes were detected in various isolates by
PCR, with feed isolates had the highest positive rate detected. Identified AR
gene carriers involved 18 bacterial genera. Selected AR genes led to acquired
resistance in other bacteria by transformation. The AR traits in many isolates
were stable in the absence of selective pressure. AR-rich feed and possibly
environmental factors may contribute to AR in the aquaculture ecosystem. For
minimum inhibitory concentration test, brain heart infusion medium was found more
suitable for majority of the bacteria examined than cation-adjusted Mueller
Hinton broth, with latter being the recommended medium for clinical isolates by
standard protocol. The data indicated a need to update the methodology due to
genetic diversity of microbiota for better understanding of the AR ecology.
PMID- 26441860
TI - Prevalence and distribution of soil-borne zoonotic pathogens in Lahore district
of Pakistan.
AB - A multidisciplinary, collaborative project was conducted to determine the
prevalence and distribution of soil-borne zoonotic pathogens in Lahore district
of Pakistan and ascertain its Public Health Significance. Using a grid-based
sampling strategy, soil samples (n = 145) were collected from villages (n = 29, 5
samples/village) and examined for Bacillus anthracis, Burkholderia
mallei/pseudomallei, Coxiella burnetii, Francisella tularensis, and Yersinia
pestis using real time PCR assays. Chemical analysis of soil samples was also
performed on these samples. The relationship between soil composition and absence
or presence of the pathogen, and seven risk factors was evaluated. DNA of B.
anthracis (CapB), B. mallei/pseudomallei (chromosomal gene), C. burnetii (IS1111,
transposase gene), and F. tularensis (lipoprotein/outer membrane protein) was
detected in 9.6, 1.4, 4.8, and 13.1% of soil samples, respectively. None of the
samples were positive for protective antigen plasmid (PA) of B. anthracis and Y.
pestis (plasminogen activating factor, pPla gene). The prevalence of B. anthracis
(CapB) was found to be associated with organic matter, magnesium (Mg), copper
(Cu), chromium (Cr), manganese (Mn), cobalt (Co), cadmium (Cd), sodium (Na),
ferrous (Fe), calcium (Ca), and potassium (K). Phosphorous (P) was found to be
associated with prevalence of F. tularensis while it were Mg, Co, Na, Fe, Ca, and
K for C. burnetii. The odds of detecting DNA of F. tularensis were 2.7, 4.1, and
2.7 higher when soil sample sites were >1 km from animal markets, >500 m from
vehicular traffic roads and animal density of < 1000 animals, respectively. While
the odds of detecting DNA of C. burnetii was 32, 11.8, and 5.9 higher when soil
sample sites were >500 m from vehicular traffic roads, presence of ground cover
and animal density of < 1000 animals, respectively. In conclusion, the
distribution pattern of the soil-borne pathogens in and around the areas of
Lahore district puts both human and animal populations at a high risk of
exposure. Further studies are needed to explore the genetic nature and molecular
diversity of prevailing pathogens together with their seroconversion in animals
and humans.
PMID- 26441861
TI - The human gut virome: a multifaceted majority.
AB - Here, we outline our current understanding of the human gut virome, in particular
the phage component of this ecosystem, highlighting progress, and challenges in
viral discovery in this arena. We reveal how developments in high-throughput
sequencing technologies and associated data analysis methodologies are helping to
illuminate this abundant 'biological dark matter.' Current evidence suggests that
the human gut virome is a highly individual but temporally stable collective,
dominated by phages exhibiting a temperate lifestyle. This viral community also
appears to encode a surprisingly rich functional repertoire that confers a range
of attributes to their bacterial hosts, ranging from bacterial virulence and
pathogenesis to maintaining host-microbiome stability and community resilience.
Despite the significant advances in our understanding of the gut virome in recent
years, it is clear that we remain in a period of discovery and revelation, as new
methods and technologies begin to provide deeper understanding of the inherent
ecological characteristics of this viral ecosystem. As our understanding
increases, the nature of the multi-partite interactions occurring between host
and microbiome will become clearer, helping us to more rationally define the
concepts and principles that will underpin approaches to using human gut virome
components for medical or biotechnological applications.
PMID- 26441862
TI - Serological response and diagnostic value of recombinant candida cell wall
protein enolase, phosphoglycerate kinase, and beta-glucosidase.
AB - There are no specific signs and symtoms for invasive candidiasis (IC), which
makes its diagnosis a challenge. Efforts have been made for decades to establish
serological assays for rapid diagnosis of IC, but none of them have found
widespread clinical use. Using a systemic candiasis murine model, serological
response to recombinant proteins of enolase (rEno1), phosphoglycerate kinase
(rPgk1), and beta-glucosidase (rBgl2) were evaluated and rEno1 was found to
possess the strongest immunoreactivity, followed by rPgk1 and rBgl2. Likewise,
IgG antibody titers to rEno1, rPgk1, and rBgl2 in the positive sera of proven IC
patients were determined by ELISA. Results show anti-rEno1 antibody possesses the
highest titer, followed by rPgk1 and rBgl2. Antibodies against rEno1, rPgk1, and
rBgl2 were detected by ELISA tests in a group of 52 proven IC patients or 50
healthy subjects, The sensitivity, specificity, positive and negative predictive
values were 88.5, 90.0, 90.2, and 88.2% for anti-rEno1 detection, 86.5, 92.0,
91.8, and 86.8% for anti-rPgk1 detection, and 80.8, 90.0, 89.4, and 81.8% for
anti-rBgl2 detection, respectively. The data clearly demonstrate that the
recombinant proteins of Eno1, Pgk1, and Bgl2 are promising candidates for IC
serodiagnosis. There's great possibility that the recombinant Eno1 will be more
applicable in serodiagnosis and vaccine research on account of its strong
serological response.
PMID- 26441863
TI - Regulation of arsenite oxidation by the phosphate two-component system PhoBR in
Halomonas sp. HAL1.
AB - Previously, the expression of arsenite [As(III)] oxidase genes aioBA was reported
to be regulated by a three-component regulatory system, AioXSR, in a number of
As(III)-oxidizing bacterial strains. However, the regulation mechanism is still
unknown when aioXSR genes are absent in some As(III)-oxidizing bacterial genomes,
such as in Halomonas sp. HAL1. In this study, transposon mutagenesis and gene
knock-out mutation were performed, and two mutants, HAL1-phoR 931 and HAL1-?phoB,
were obtained in strain HAL1. The phoR and phoB constitute a two-component system
which is responsible for phosphate (Pi) acquisition and assimilation. Both of the
mutants showed negative As(III)-oxidation phenotypes in low Pi condition (0.1 mM)
but not under normal Pi condition (1 mM). The phoBR complementation strain HAL1
?phoB-C reversed the mutants' null phenotypes back to wild type status.
Meanwhile, lacZ reporter fusions using pCM-lacZ showed that the expression of
phoBR and aioBA were both induced by As(III) but were not induced in HAL1-phoR
931 and HAL1-?phoB. Using 15 consensus Pho box sequences, a putative Pho box was
found in the aioBA regulation region. PhoB was able to bind to the putative Pho
box in vivo (bacterial one-hybrid detection) and in vitro (electrophoretic
mobility gel shift assay), and an 18-bp binding sequence containing nine
conserved bases were determined. This study provided the evidence that PhoBR
regulates the expression of aioBA in Halomonas sp. HAL1 under low Pi condition.
The new regulation model further implies the close metabolic connection between
As and Pi.
PMID- 26441865
TI - Systemic responses in a tolerant olive (Olea europaea L.) cultivar upon root
colonization by the vascular pathogen Verticillium dahliae.
AB - Verticillium wilt of olive (VWO) is caused by the vascular pathogen Verticillium
dahliae. One of the best VWO management measures is the use of tolerant
cultivars; however, our knowledge on VWO tolerance/resistance genetics is very
limited. A transcriptomic analysis was conducted to (i) identify systemic defense
responses induced/repressed in aerial tissues of the tolerant cultivar Frantoio
upon root colonization by V. dahliae, and (ii) determine the expression pattern
of selected defense genes in olive cultivars showing differential susceptibility
to VWO. Two suppression subtractive hybridization cDNA libraries, enriched in up
regulated (FU) and down-regulated (FD) genes respectively, were generated from
"Frantoio" aerial tissues. Results showed that broad systemic transcriptomic
changes are taking place during V. dahliae-"Frantoio" interaction. A total of 585
FU and 381 FD unigenes were identified, many of them involved in defense response
to (a)biotic stresses. Selected genes were then used to validate libraries and
evaluate their temporal expression pattern in "Frantoio." Four defense genes were
analyzed in cultivars Changlot Real (tolerant) and Picual (susceptible). An
association between GRAS1 and DRR2 gene expression patterns and susceptibility to
VWO was observed, suggesting that these transcripts could be further evaluated as
markers of the tolerance level of olive cultivars to V. dahliae.
PMID- 26441864
TI - Interplay between the alpharetroviral Gag protein and SR proteins SF2 and SC35 in
the nucleus.
AB - Retroviruses are positive-sense, single-stranded RNA viruses that reverse
transcribe their RNA genomes into double-stranded DNA for integration into the
host cell chromosome. The integrated provirus is used as a template for the
transcription of viral RNA. The full-length viral RNA can be used for the
translation of the Gag and Gag-Pol structural proteins or as the genomic RNA
(gRNA) for encapsidation into new virions by the Gag protein. The mechanism by
which Gag selectively incorporates unspliced gRNA into virus particles is poorly
understood. Although Gag was previously thought to localize exclusively to the
cytoplasm and plasma membrane where particles are released, we found that the Gag
protein of Rous sarcoma virus, an alpharetrovirus, undergoes transient nuclear
trafficking. When the nuclear export signal of RSV Gag is mutated (Gag.L219A),
the protein accumulates in discrete subnuclear foci reminiscent of nuclear bodies
such as splicing speckles, paraspeckles, and PML bodies. In this report, we
observed that RSV Gag.L219A foci appeared to be tethered in the nucleus,
partially co-localizing with the splicing speckle components SC35 and SF2.
Overexpression of SC35 increased the number of Gag.L219A nucleoplasmic foci,
suggesting that SC35 may facilitate the formation of Gag foci. We previously
reported that RSV Gag nuclear trafficking is required for efficient gRNA
packaging. Together with the data presented herein, our findings raise the
intriguing hypothesis that RSV Gag may co-opt splicing factors to localize near
transcription sites. Because splicing occurs co-transcriptionally, we speculate
that this mechanism could allow Gag to associate with unspliced viral RNA shortly
after its transcription initiation in the nucleus, before the viral RNA can be
spliced or exported from the nucleus as an mRNA template.
PMID- 26441866
TI - Extensive in silico analysis of Mimivirus coded Rab GTPase homolog suggests a
possible role in virion membrane biogenesis.
AB - Rab GTPases are the key regulators of intracellular membrane trafficking in
eukaryotes. Many viruses and intracellular bacterial pathogens have evolved to
hijack the host Rab GTPase functions, mainly through activators and effector
proteins, for their benefit. Acanthamoeba polyphaga mimivirus (APMV) is one of
the largest viruses and belongs to the monophyletic clade of nucleo-cytoplasmic
large DNA viruses (NCLDV). The inner membrane lining is integral to the APMV
virion structure. APMV assembly involves extensive host membrane modifications,
like vesicle budding and fusion, leading to the formation of a membrane sheet
that is incorporated into the virion. Intriguingly, APMV and all group I members
of the Mimiviridae family code for a putative Rab GTPase protein. APMV is the
first reported virus to code for a Rab GTPase (encoded by R214 gene). Our
thorough in silico analysis of the subfamily specific (SF) region of Mimiviridae
Rab GTPase sequences suggests that they are related to Rab5, a member of the
group II Rab GTPases, of lower eukaryotes. Because of their high divergence from
the existing three isoforms, A, B, and C of the Rab5-family, we suggest that
Mimiviridae Rabs constitute a new isoform, Rab5D. Phylogenetic analysis indicated
probable horizontal acquisition from a lower eukaryotic ancestor followed by
selection and divergence. Furthermore, interaction network analysis suggests that
vps34 (a Class III PI3K homolog, coded by APMV L615), Atg-8 and dynamin (host
proteins) are recruited by APMV Rab GTPase during capsid assembly. Based on these
observations, we hypothesize that APMV Rab plays a role in the acquisition of
inner membrane during virion assembly.
PMID- 26441867
TI - Seeking sunlight: rapid phototactic motility of filamentous mat-forming
cyanobacteria optimize photosynthesis and enhance carbon burial in Lake Huron's
submerged sinkholes.
AB - We studied the motility of filamentous mat-forming cyanobacteria consisting
primarily of Oscillatoria-like cells growing under low-light, low-oxygen, and
high-sulfur conditions in Lake Huron's submerged sinkholes using in situ
observations, in vitro measurements and time-lapse microscopy. Gliding movement
of the cyanobacterial trichomes (100-10,000 MUm long filaments, composed of cells
~10 MUm wide and ~3 MUm tall) revealed individual as well as group-coordinated
motility. When placed in a petri dish and dispersed in ground water from the
sinkhole, filaments re-aggregated into defined colonies within minutes, then
dispersed again. Speed of individual filaments increased with temperature from
~50 MUm min(-1) or ~15 body lengths min(-1) at 10 degrees C to ~215 MUm min(-1)
or ~70 body lengths min(-1) at 35 degrees C - rates that are rapid relative to
non-flagellated/ciliated microbes. Filaments exhibited precise and coordinated
positive phototaxis toward pinpoints of light and congregated under the light of
foil cutouts. Such light-responsive clusters showed an increase in photosynthetic
yield - suggesting phototactic motility aids in light acquisition as well as
photosynthesis. Once light source was removed, filaments slowly spread out evenly
and re-aggregated, demonstrating coordinated movement through inter-filament
communication regardless of light. Pebbles and pieces of broken shells placed
upon intact mat were quickly covered by vertically motile filaments within hours
and became fully buried in the anoxic sediments over 3-4 diurnal cycles - likely
facilitating the preservation of falling debris. Coordinated horizontal and
vertical filament motility optimize mat cohesion and dynamics, photosynthetic
efficiency and sedimentary carbon burial in modern-day sinkhole habitats that
resemble the shallow seas in Earth's early history. Analogous cyanobacterial
motility may have played a key role in the oxygenation of the planet by
optimizing photosynthesis while favoring carbon burial.
PMID- 26441868
TI - Interactive effects of cocaine on HIV infection: implication in HIV-associated
neurocognitive disorder and neuroAIDS.
AB - Substantial epidemiological studies suggest that not only, being one of the
reasons for the transmission of the human immunodeficiency virus (HIV), but drug
abuse also serves its role in determining the disease progression and severity
among the HIV infected population. This article focuses on the drug cocaine, and
its role in facilitating entry of HIV into the CNS and mechanisms of development
of neurologic complications in infected individuals. Cocaine is a powerfully
addictive central nervous system stimulating drug, which increases the level of
neurotransmitter dopamine (DA) in the brain, by blocking the dopamine
transporters (DAT) which is critical for DA homeostasis and neurocognitive
function. Tat protein of HIV acts as an allosteric modulator of DAT, where as
cocaine acts as reuptake inhibitor. When macrophages in the CNS are exposed to
DA, their number increases. These macrophages release inflammatory mediators and
neurotoxins, causing chronic neuroinflammation. Cocaine abuse during HIV
infection enhances the production of platelet monocyte complexes (PMCs), which
may cross transendothelial barrier, and result in HIV-associated neurocognitive
disorder (HAND). HAND is characterized by neuroinflammation, including
astrogliosis, multinucleated giant cells, and neuronal apoptosis that is linked
to progressive virus infection and immune deterioration. Cocaine and viral
proteins are capable of eliciting signaling transduction pathways in neurons,
involving in mitochondrial membrane potential loss, oxidative stress, activation
of JNK, p38, and ERK/MAPK pathways, and results in downstream activation of NF
kappaB that leads to HAND. Tat-induced inflammation provokes permeability of the
blood brain barrier (BBB) in the platelet dependent manner, which can potentially
be the reason for progression to HAND during HIV infection. A better
understanding on the role of cocaine in HIV infection can give a clue in
developing novel therapeutic strategies against HIV-1 infection in cocaine using
HIV infected population.
PMID- 26441869
TI - Genetic determinants of heat resistance in Escherichia coli.
AB - Escherichia coli AW1.7 is a heat resistant food isolate and the occurrence of
pathogenic strains with comparable heat resistance may pose a risk to food
safety. To identify the genetic determinants of heat resistance, 29 strains of E.
coli that differed in their of heat resistance were analyzed by comparative
genomics. Strains were classified as highly heat resistant strains, exhibiting a
D60-value of more than 6 min; moderately heat resistant strains, exhibiting a D60
value of more than 1 min; or as heat sensitive. A ~14 kb genomic island
containing 16 predicted open reading frames encoding putative heat shock proteins
and proteases was identified only in highly heat resistant strains. The genomic
island was termed the locus of heat resistance (LHR). This putative operon is
flanked by mobile elements and possesses >99% sequence identity to genomic
islands contributing to heat resistance in Cronobacter sakazakii and Klebsiella
pneumoniae. An additional 41 LHR sequences with >87% sequence identity were
identified in 11 different species of beta- and gamma-proteobacteria. Cloning of
the full length LHR conferred high heat resistance to the heat sensitive E. coli
AW1.7DeltapHR1 and DH5alpha. The presence of the LHR correlates perfectly to heat
resistance in several species of Enterobacteriaceae and occurs at a frequency of
2% of all E. coli genomes, including pathogenic strains. This study suggests the
LHR has been laterally exchanged among the beta- and gamma-proteobacteria and is
a reliable indicator of high heat resistance in E. coli.
PMID- 26441870
TI - Diversity of laccase-coding genes in Fusarium oxysporum genomes.
AB - Multiple studies confirm laccase role in fungal pathogenicity and lignocellulose
degradation. In spite of broad genomic research, laccases from plant wilt
pathogen Fusarium oxysporum are still not characterized. The study aimed to
identify F. oxysporum genes that may encode laccases sensu stricto and to
characterize the proteins in silico in order to facilitate further research on
their impact on the mentioned processes. Twelve sequenced F. oxysporum genomes
available on Broad Institute of Harvard and MIT (2015) website were analyzed and
three genes that may encode laccases sensu stricto were found. Their amino acid
sequences possess all features essential for their catalytic activity, moreover,
the homology models proved the characteristic 3D laccase structures. The study
shades light on F. oxysporum as a new source of multicopper oxidases, enzymes
with possible high redox potential and broad perspective in biotechnological
applications.
PMID- 26441871
TI - Adaptation strategies of endolithic chlorophototrophs to survive the hyperarid
and extreme solar radiation environment of the Atacama Desert.
AB - The Atacama Desert, northern Chile, is one of the driest deserts on Earth and, as
such, a natural laboratory to explore the limits of life and the strategies
evolved by microorganisms to adapt to extreme environments. Here we report the
exceptional adaptation strategies of chlorophototrophic and eukaryotic algae, and
chlorophototrophic and prokaryotic cyanobacteria to the hyperarid and extremely
high solar radiation conditions occurring in this desert. Our approach combined
several microscopy techniques, spectroscopic analytical methods, and molecular
analyses. We found that the major adaptation strategy was to avoid the extreme
environmental conditions by colonizing cryptoendolithic, as well as,
hypoendolithic habitats within gypsum deposits. The cryptoendolithic colonization
occurred a few millimeters beneath the gypsum surface and showed a succession of
organized horizons of algae and cyanobacteria, which has never been reported for
endolithic microbial communities. The presence of cyanobacteria beneath the algal
layer, in close contact with sepiolite inclusions, and their hypoendolithic
colonization suggest that occasional liquid water might persist within these sub
microhabitats. We also identified the presence of abundant carotenoids in the
upper cryptoendolithic algal habitat and scytonemin in the cyanobacteria
hypoendolithic habitat. This study illustrates that successful lithobiontic
microbial colonization at the limit for microbial life is the result of a
combination of adaptive strategies to avoid excess solar irradiance and extreme
evapotranspiration rates, taking advantage of the complex structural and
mineralogical characteristics of gypsum deposits-conceptually called "rock's
habitable architecture." Additionally, self-protection by synthesis and
accumulation of secondary metabolites likely produces a shielding effect that
prevents photoinhibition and lethal photooxidative damage to the
chlorophototrophs, representing another level of adaptation.
PMID- 26441872
TI - Impact of CO2 leakage from sub-seabed carbon dioxide capture and storage (CCS)
reservoirs on benthic virus-prokaryote interactions and functions.
AB - Atmospheric CO2 emissions are a global concern due to their predicted impact on
biodiversity, ecosystems functioning, and human life. Among the proposed
mitigation strategies, CO2 capture and storage, primarily the injection of CO2
into marine deep geological formations has been suggested as a technically
practical option for reducing emissions. However, concerns have been raised that
possible leakage from such storage sites, and the associated elevated levels of
pCO2 could locally impact the biodiversity and biogeochemical processes in the
sediments above these reservoirs. Whilst a number of impact assessment studies
have been conducted, no information is available on the specific responses of
viruses and virus-host interactions. In the present study, we tested the impact
of a simulated CO2 leakage on the benthic microbial assemblages, with specific
focus on microbial activity and virus-induced prokaryotic mortality (VIPM). We
found that exposure to levels of CO2 in the overlying seawater from 1,000 to
20,000 ppm for a period up to 140 days, resulted in a marked decrease in
heterotrophic carbon production and organic matter degradation rates in the
sediments, associated with lower rates of VIPM, and a progressive accumulation of
sedimentary organic matter with increasing CO2 concentrations. These results
suggest that the increase in seawater pCO2 levels that may result from CO2
leakage, can severely reduce the rates of microbial-mediated recycling of the
sedimentary organic matter and viral infections, with major consequences on C
cycling and nutrient regeneration, and hence on the functioning of benthic
ecosystems.
PMID- 26441873
TI - Biochemistry and genetics of ACC deaminase: a weapon to "stress ethylene"
produced in plants.
AB - 1-aminocyclopropane-1-carboxylate deaminase (ACCD), a pyridoxal phosphate
dependent enzyme, is widespread in diverse bacterial and fungal species. Owing to
ACCD activity, certain plant associated bacteria help plant to grow under biotic
and abiotic stresses by decreasing the level of "stress ethylene" which is
inhibitory to plant growth. ACCD breaks down ACC, an immediate precursor of
ethylene, to ammonia and alpha-ketobutyrate, which can be further metabolized by
bacteria for their growth. ACC deaminase is an inducible enzyme whose synthesis
is induced in the presence of its substrate ACC. This enzyme encoded by gene AcdS
is under tight regulation and regulated differentially under different
environmental conditions. Regulatory elements of gene AcdS are comprised of the
regulatory gene encoding LRP protein and other regulatory elements which are
activated differentially under aerobic and anaerobic conditions. The role of some
additional regulatory genes such as AcdB or LysR may also be required for
expression of AcdS. Phylogenetic analysis of AcdS has revealed that distribution
of this gene among different bacteria might have resulted from vertical gene
transfer with occasional horizontal gene transfer (HGT). Application of bacterial
AcdS gene has been extended by developing transgenic plants with ACCD gene which
showed increased tolerance to biotic and abiotic stresses in plants. Moreover,
distribution of ACCD gene or its homolog's in a wide range of species belonging
to all three domains indicate an alternative role of ACCD in the physiology of an
organism. Therefore, this review is an attempt to explore current knowledge of
bacterial ACC deaminase mediated physiological effects in plants, mode of enzyme
action, genetics, distribution among different species, ecological role of ACCD
and, future research avenues to develop transgenic plants expressing foreign AcdS
gene to cope with biotic and abiotic stressors. Systemic identification of
regulatory circuits would be highly valuable to express the gene under diverse
environmental conditions.
PMID- 26441874
TI - Flow cytometric evaluation of physico-chemical impact on Gram-positive and Gram
negative bacteria.
AB - Since heat sensitivity of fruits and vegetables limits the application of thermal
inactivation processes, new emerging inactivation technologies have to be
established to fulfill the requirements of food safety without affecting the
produce quality. The efficiency of inactivation treatments has to be ensured and
monitored. Monitoring of inactivation effects is commonly performed using
traditional cultivation methods which have the disadvantage of the time span
needed to obtain results. The aim of this study was to compare the inactivation
effects of peracetic acid (PAA), ozonated water (O3), and cold atmospheric
pressure plasma (CAPP) on Gram-positive and Gram-negative bacteria using flow
cytometric methods. E. coli cells were completely depolarized after treatment (15
s) with 0.25% PAA at 10 degrees C, and after treatment (10 s) with 3.8 mg l(-1)
O3 at 12 degrees C. The membrane potential of CAPP treated cells remained almost
constant at an operating power of 20 W over a time period of 3 min, and
subsequently decreased within 30 s of further treatment. Complete membrane
permeabilization was observed after 10 s O3 treatment, but treatment with PAA and
CAPP did not completely permeabilize the cells within 2 and 4 min, respectively.
Similar results were obtained for esterase activity. O3 inactivates cellular
esterase but esterase activity was detected after 4 min CAPP treatment and 2 min
PAA treatment. L. innocua cells and P. carotovorum cells were also permeabilized
instantaneously by O3 treatment at concentrations of 3.8 +/- 1 mg l(-1). However,
higher membrane permeabilization of L. innocua and P. carotovorum than of E. coli
was observed at CAPP treatment of 20 W. The degree of bacterial damage due to the
inactivation processes is highly dependent on treatment parameters as well as on
treated bacteria. Important information regarding the inactivation mechanisms can
be obtained by flow cytometric measurements and this enables the definition of
critical process parameters.
PMID- 26441875
TI - Nonlinear electrical impedance spectroscopy of viruses using very high electric
fields created by nanogap electrodes.
AB - Our living sphere is constantly exposed to a wide range of pathogenic viruses,
which can be either known, or of novel origin. Currently, there is no methodology
for continuously monitoring the environment for viruses in general, much less a
methodology that allows the rapid and sensitive identification of a wide variety
of viruses responsible for communicable diseases. Traditional approaches, based
on PCR and immunodetection systems, only detect known or specifically targeted
viruses. We here describe a simple device that can potentially detect any virus
between nanogap electrodes using nonlinear impedance spectroscopy. Three test
viruses, differing in shape and size, were used to demonstrate the general
applicability of this approach: baculovirus, tobacco mosaic virus (TMV), and
influenza virus. We show that each of the virus types responded differently in
the nanogap to changes in the electric field strength, and the impedance of the
virus solutions differed depending both on virus type and virus concentration.
These preliminary results show that the three virus types can be distinguished
and their approximate concentrations determined. Although further studies are
required, the proposed nonlinear impedance spectroscopy method may achieve a
sensitivity comparable to that of more traditional, but less versatile, virus
detection systems.
PMID- 26441876
TI - Co-occurrence of Methanosarcina mazei and Geobacteraceae in an iron (III)
reducing enrichment culture.
AB - Methanosaeta harundinacea and Methanosarcina barkeri, known as classic
acetoclastic methanogens, are capable of directly accepting electrons from
Geobacter metallireducens for the reduction of carbon dioxide to methane, having
been revealed as direct interspecies electron transfer (DIET) in the laboratory
co-cultures. However, whether their co-occurrences are ubiquitous in the iron
(III)-reducing environments and the other species of acetoclastic methanogens
such as Methanosarcina mazei are capable of DIET are still unknown. Instead of
initiating the co-cultures with pure cultures, two-step cultivation was employed
to selectively enrich iron (III)-reducing microorganisms in a coastal gold mining
river, Jiehe River, with rich iron content in the sediments. First, iron (III)
reducers including Geobacteraceae were successfully enriched by 3-months
successive culture on amorphous Fe(III) oxides as electron acceptor and acetate
as electron donor. High-throughput Illumina sequencing, terminal restriction
fragment length polymorphism (T-RFLP) and clone library analysis based on 16S
rRNA genes revealed that the enrichment cultures actively contained the bacteria
belong to Geobacteraceae and Bacilli, exclusively dominated by the archaea belong
to Methanosarcinaceae. Second, the enrichment cultures including methanogens and
Geobacteraceae were transferred with ethanol as alternative electron donor.
Remarkably, aggregates were successively formed in the enrichments after three
transfers. The results revealed by RNA-based analysis demonstrate that the co
occurrence of Methanosarcina mazei and Geobacteraceae in an iron (III)-reducing
enrichment culture. Furthermore, the aggregates, as close physical contact,
formed in the enrichment culture, indicate that DIET could be a possible option
for interspecies electron transfer in the aggregates.
PMID- 26441877
TI - Halo(natrono)archaea isolated from hypersaline lakes utilize cellulose and chitin
as growth substrates.
AB - Until recently, extremely halophilic euryarchaeota were considered mostly as
aerobic heterotrophs utilizing simple organic compounds as growth substrates.
Almost nothing is known on the ability of these prokaryotes to utilize complex
polysaccharides, such as cellulose, xylan, and chitin. Although few haloarchaeal
cellulases and chitinases were recently characterized, the analysis of currently
available haloarchaeal genomes deciphered numerous genes-encoding glycosidases of
various families including endoglucanases and chitinases. However, all these
haloarchaea were isolated and cultivated on simple substrates and their ability
to grow on polysaccharides in situ or in vitro is unknown. This study examines
several halo(natrono)archaeal strains from geographically distant hypersaline
lakes for the ability to grow on insoluble polymers as a sole growth substrate in
salt-saturated mineral media. Some of them belonged to known taxa, while other
represented novel phylogenetic lineages within the class Halobacteria. All
isolates produced extracellular extremely salt-tolerant cellulases or chitinases,
either cell-free or cell-bound. Obtained results demonstrate a presence of
diverse populations of haloarchaeal cellulo/chitinotrophs in hypersaline habitats
indicating that euryarchaea participate in aerobic mineralization of recalcitrant
organic polymers in salt-saturated environments.
PMID- 26441878
TI - Recombinant expression library of Pyrococcus furiosus constructed by high
throughput cloning: a useful tool for functional and structural genomics.
AB - Hyperthermophile Pyrococcus furiosus grows optimally near 100 degrees C and is an
important resource of many industrial and molecular biological enzymes. To study
the structure and function of P. furiosus proteins at whole genome level, we
constructed expression plasmids of each P. furiosus gene using a ligase
independent cloning method, which was based on amplifying target gene and vector
by PCR using phosphorothioate-modified primers and digesting PCR products by
lambda exonuclease. Our cloning method had a positive clone percentage of >= 80%
in 96-well plate cloning format. Small-scale expression experiment showed that 55
out of 80 genes were efficiently expressed in Escherichia coli Strain Rosetta
2(DE3)pLysS. In summary, this recombinant expression library of P. furiosus
provides a platform for functional and structural studies, as well as developing
novel industrial enzymes. Our cloning scheme is adaptable to constructing
recombinant expression library of other sequenced organisms.
PMID- 26441879
TI - Geriatric Respondents and Non-Respondents to Probiotic Intervention Can be
Differentiated by Inherent Gut Microbiome Composition.
AB - SCOPE: Probiotic interventions are known to have been shown to influence the
composition of the intestinal microbiota in geriatrics. The growing concern is
the apparent variation in response to identical strain dosage among human
volunteers. One factor that governs this variation is the host gut microbiome. In
this study, we attempted to define a core gut metagenome, which could act as a
predisposition signature marker of inherent bacterial community that can help
predict the success of a probiotic intervention. METHODS AND RESULTS: To
characterize the geriatric gut microbiome, we designed primers targeting the 16S
rRNA hypervariable region V2-V3 followed by semiconductor sequencing using Ion
Torrent PGM. Among respondents and non-respondents, the chief genera of phylum
Firmicutes that showed significant differences are Lactobacillus, Clostridium,
Eubacterium, and Blautia (q < 0.002), while in the genera of phylum
Proteobacteria included Shigella, Escherichia, Burkholderia and Camphylobacter (q
< 0.002). CONCLUSION: We have identified potential microbial biomarkers and
taxonomic patterns that correlate with a positive response to probiotic
intervention in geriatric volunteers. Future work with larger cohorts of
geriatrics with diverse dietary influences could reveal the potential of the
signature patterns of microbiota for personalized nutrition.
PMID- 26441881
TI - Antibiotic resistance and mecA characterization of coagulase-negative
staphylococci isolated from three hotels in London, UK.
AB - Antibiotic resistance in bacteria isolated from non-healthcare environments, is a
potential problem to public health. In our survey a total of 71 coagulase
negative staphylococci (CNS) belonging to 11 different species were isolated from
three large hotels in London, UK. The most prevalent species was Staphylococcus
haemolyticus, with S. hominis, S. warneri, S. cohnii, and Staphylococcus
epidermidis commonly detected. Antimicrobial susceptibilities and carriage of the
mecA gene were determined for all of these isolates. Most (85.9%) staphylococci
were resistant to multiple antibiotics with all displaying increased
susceptibility toward penicillin, fusidic acid, erythromycin, and cefepime.
Twenty-one (29.5%) of the isolates were mecA positive, however MIC values to
oxacillin, normally associated with the carriage of mecA, varied widely in this
group (from 0.06 to 256 mg/L). Fifteen of the twenty-one mecA positive isolates
carried SCCmec of these seven were type V, one type I, one type II, and one type
IV. Additionally, five of these 15 isolates carried a previously unreported type,
1A, which involves an association between class A mec complex and ccr type 1. The
remaining six of the 21 isolates were non-typeable and carried a combination of
class A mec complex and ccrC. In addition to this, we also report on new MLST
types which were assigned for five S. epidermidis isolates. Four out of these
five isolates had MICs between 0.06 and 256 mg/L to oxacillin and would be
regarded as clinically susceptible but one isolate had a high oxacillin MIC of
256 mg/L. We demonstrated widespread multiple drug resistance among different
staphylococcal species isolated from non-healthcare environments highlighting the
potential for these species to act as a reservoir for methicillin and other forms
of drug resistance.
PMID- 26441880
TI - Legume-rhizobia signal exchange: promiscuity and environmental effects.
AB - Although signal exchange between legumes and their rhizobia is among the best
known examples of this biological process, most of the more characterized data
comes from just a few legume species and environmental stresses. Although a
relative wealth of information is available for some model legumes and some of
the major pulses such as soybean, little is known about tropical legumes. This
relative disparity in current knowledge is also apparent in the research on the
effects of environmental stress on signal exchange; cool-climate stresses, such
as low-soil temperature, comprise a relatively large body of research, whereas
high-temperature stresses and drought are not nearly as well understood. Both
tropical legumes and their environmental stress-induced effects are increasingly
important due to global population growth (the demand for protein), climate
change (increasing temperatures and more extreme climate behavior), and
urbanization (and thus heavy metals). This knowledge gap for both legumes and
their environmental stresses is compounded because whereas most temperate legume
rhizobia symbioses are relatively specific and cultivated under relatively stable
environments, the converse is true for tropical legumes, which tend to be
promiscuous, and grow in highly variable conditions. This review will clarify
some of this missing information and highlight fields in which further research
would benefit our current knowledge.
PMID- 26441884
TI - Spontaneous large-scale autolysis in Clostridium acetobutylicum contributes to
generation of more spores.
AB - Autolysis is a widespread phenomenon in bacteria. In batch fermentation of
Clostridium acetobutylicum ATCC 824, there is a spontaneous large-scale autolysis
phenomenon with significant decrease of cell density immediately after
exponential phase. To unravel the role of autolysis, an autolysin-coding gene,
CA_C0554, was disrupted by using ClosTron system to obtain the mutant C.
acetobutylicum lyc::int(72). The lower final cell density and faster cell density
decrease rate of C. acetobutylicum ATCC 824 than those of C. acetobutylicum
lyc::int(72) indicates that CA_C0554 was an important but not the sole autolysin
coding gene responding for the large-scale autolysis. Similar glucose utilization
and solvents production but obvious lower cell density of C. acetobutylicum ATCC
824 comparing to C. acetobutylicum lyc::int(72) suggests that lysed C.
acetobutylicum ATCC 824 cells were metabolic inactive. On the contrary, the spore
density of C. acetobutylicum ATCC 824 is 26.1% higher than that of C.
acetobutylicum lyc::int(72) in the final culture broth of batch fermentation. We
speculated that spontaneous autolysis of metabolic-inactive cells provided
nutrients for the sporulating cells. The present study suggests that one
important biological role of spontaneous large-scale autolysis in C.
acetobutylicum ATCC 824 batch fermentation is contributing to generation of more
spores during sporulation.
PMID- 26441882
TI - Role of MRP transporters in regulating antimicrobial drug inefficacy and
oxidative stress-induced pathogenesis during HIV-1 and TB infections.
AB - Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette
(ABC) drug-efflux transporter superfamily. MRPs are known to regulate the
efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active
antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus
Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated
drugs, MRPs can also regulate cellular oxidative stress, which may contribute to
both HIV and/or TB pathogenesis. This review focuses on the characteristics,
functional expression, and modulation of known members of the MRP family in HIV
infected cells exposed to ARV drugs and discusses their known role in drug
inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP
family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most
extensively studied. Details of the other members of this family have not been
known until recently, but differential expression has been documented in
inflammatory tissues. Researchers have found that the distribution, function, and
reactivity of members of MRP family vary in different types of lymphocytes and
macrophages, and are differentially expressed at the basal and apical surfaces of
both endothelial and epithelial cells. Therefore, the prime objective of this
review is to delineate the role of MRP transporters in HAART and TB therapy and
their potential in precipitating cellular dysfunctions manifested in these
chronic infectious diseases. We also provide an overview of different available
options and novel experimental strategies that are being utilized to overcome the
drug resistance and disease pathogenesis mediated by these membrane transporters.
PMID- 26441885
TI - Cooperative pathogenicity in cystic fibrosis: Stenotrophomonas maltophilia
modulates Pseudomonas aeruginosa virulence in mixed biofilm.
AB - The present study was undertaken in order to understand more about the
interaction occurring between S. maltophilia and P. aeruginosa, which are
frequently co-isolated from CF airways. For this purpose, S. maltophilia RR7 and
P. aeruginosa RR8 strains, co-isolated from the lung of a chronically infected CF
patient during a pulmonary exacerbation episode, were evaluated for reciprocal
effect during planktonic growth, adhesion and biofilm formation onto both
polystyrene and CF bronchial cell monolayer, motility, as well as for gene
expression in mixed biofilms. P. aeruginosa significantly affected S. maltophilia
growth in both planktonic and biofilm cultures, due to an inhibitory activity
probably requiring direct contact. Conversely, no effect was observed on P.
aeruginosa by S. maltophilia. Compared with monocultures, the adhesiveness of P.
aeruginosa on CFBE41o- cells was significantly reduced by S. maltophilia, which
probably acts by reducing P. aeruginosa's swimming motility. An opposite trend
was observed for biofilm formation, confirming the findings obtained using
polystyrene. When grown in mixed biofilm with S. maltophilia, P. aeruginosa
significantly over-expressed aprA, and algD-codifying for protease and alginate,
respectively-while the quorum sensing related rhlR and lasI genes were down
regulated. The induced alginate expression by P. aeruginosa might be responsible
for the protection of S. maltophilia against tobramycin activity we observed in
mixed biofilms. Taken together, our results suggest that the existence of
reciprocal interference of S. maltophilia and P. aeruginosa in CF lung is
plausible. In particular, S. maltophilia might confer some selective "fitness
advantage" to P. aeruginosa under the specific conditions of chronic infection
or, alternatively, increase the virulence of P. aeruginosa thus leading to
pulmonary exacerbation.
PMID- 26441883
TI - Regulatory principles governing Salmonella and Yersinia virulence.
AB - Enteric pathogens such as Salmonella and Yersinia evolved numerous strategies to
survive and proliferate in different environmental reservoirs and mammalian
hosts. Deciphering common and pathogen-specific principles for how these bacteria
adjust and coordinate spatiotemporal expression of virulence determinants, stress
adaptation, and metabolic functions is fundamental to understand microbial
pathogenesis. In order to manage sudden environmental changes, attacks by the
host immune systems and microbial competition, the pathogens employ a plethora of
transcriptional and post-transcriptional control elements, including
transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to
fine-tune and control complex gene regulatory networks. Many of the contributing
global regulators and the molecular mechanisms of regulation are frequently
conserved between Yersinia and Salmonella. However, the interplay, arrangement,
and composition of the control elements vary between these closely related
enteric pathogens, which generate phenotypic differences leading to distinct
pathogenic properties. In this overview we present common and different
regulatory networks used by Salmonella and Yersinia to coordinate the expression
of crucial motility, cell adhesion and invasion determinants, immune defense
strategies, and metabolic adaptation processes. We highlight evolutionary changes
of the gene regulatory circuits that result in different properties of the
regulatory elements and how this influences the overall outcome of the infection
process.
PMID- 26441886
TI - The vaginal isolate Lactobacillus paracasei LPC-S01 (DSM 26760) is suitable for
oral administration.
AB - Bacterial vaginosis is one of the most common urogenital diseases affecting women
in reproductive age. The administration of probiotics as vaginal suppository has
been proposed as a strategy to cure this condition and reduce its recurrence.
Nonetheless, also oral consumption of probiotics, which is a more practical route
of administration, proved to be an efficient strategy. In this perspective, we
studied Lactobacillus paracasei LPC-S01 (DSM 26760), a human vaginal isolate
included in commercial probiotic preparations for topical use, in order to assess
if this bacterium can also perform as gastrointestinal probiotic. Comparative
genomics revealed the presence of several accessory genes suggesting that LPC-S01
is a niche-generalist member of its species. According to a procedure
conventionally used to predict the probiotic potential, we demonstrated that the
probiotic properties of strain LPC-S01, with respect to those of the well-known
probiotic references L. paracasei Shirota and DG, are equal for the bile
tolerance and the reduction of NF-kappaB activation in Caco-2 cells, or superior
for the tolerance to gastric juice and the adhesion to Caco-2 epithelial cells.
We then demonstrated that LPC-S01 is susceptible to antibiotics indicated by EFSA
and does not produce biogenic amines. Finally, a double-blind cross-over pilot
intervention trial on healthy human volunteers showed that, after a 7-days oral
consumption of capsules containing about 24 billion live cells, the fecal cell
concentrations of strains LPC-S01 and DG (evaluated by qPCR) were not dissimilar.
Specifically, both probiotics' cell concentrations were above the detection limit
for an average of 5 days from the end of the treatment, corresponding to a mean
number of evacuations of 7 +/- 2. Taken together, these data demonstrate that the
vaginal isolate L. paracasei LPC-S01 possesses safety and functional properties
that may support its use as probiotic to be administered per os for potential
intestinal as well as vaginal applications.
PMID- 26441887
TI - Effect of carbon on whole-biofilm metabolic response to high doses of
streptomycin.
AB - Biofilms typically exist as complex communities comprising multiple species with
the ability to adapt to a variety of harsh conditions. In clinical settings,
antibiotic treatments based on planktonic susceptibility tests are often
ineffective against biofilm infections. Using a CO2 evolution measurement system
we delineated the real-time metabolic response in continuous flow biofilms to
streptomycin doses much greater than their planktonic susceptibilities. Stable
biofilms from a multispecies culture (containing mainly Pseudomonas aeruginosa
and Stenotrophomonas maltophilia), Gram-negative environmental isolates, and
biofilms formed by pure culture P. aeruginosa strains PAO1 and PAO1 DeltaMexXY
(minimum planktonic inhibitory concentrations between 1.5 and 3.5 mg/l), were
exposed in separate experiments to 4000 mg/l streptomycin for 4 h after which
growth medium resumed. In complex medium, early steady state multispecies
biofilms were susceptible to streptomycin exposure, inferred by a cessation of
CO2 production. However, multispecies biofilms survived high dose exposures when
there was extra carbon in the antibiotic medium, or when they were grown in
defined citrate medium. The environmental isolates and PAO1 biofilms showed
similar metabolic profiles in response to streptomycin; ceasing CO2 production
after initial exposure, with CO2 levels dropping toward baseline levels prior to
recovery back to steady state levels, while subsequent antibiotic exposure
elicited increased CO2 output. Monitoring biofilm metabolic response in real-time
allowed exploration of conditions resulting in vulnerability after antibiotic
exposure compared to the resistance displayed following subsequent exposures.
PMID- 26441888
TI - Diversity and antibiotic susceptibility of autochthonous dairy enterococci
isolates: are they safe candidates for autochthonous starter cultures?
AB - Enterococci represent the most controversial group of dairy bacteria. They are
found to be the main constituent of many traditional Mediterranean dairy products
and contribute to their characteristic taste and flavor. On the other hand,
during the last 50 years antibiotic-resistant enterococci have emerged as leading
causes of nosocomial infections worldwide. The aim of this study was to determine
the diversity, technological properties, antibiotic susceptibility and virulence
traits of 636 enterococci previously isolated from 55 artisan dairy products from
12 locations in the Western Balkan countries (WBC) of Serbia, Croatia and Bosnia
and Herzegovina. All strains were identified both by microbiological and
molecular methods. The predominant species was Enterococcus durans, followed by
Enterococcus faecalis and Enterococcus faecium. Over 44% of the isolates were
resistant to ciprofloxacin and erythromycin, while 26.2% of the isolates were
multi-resistant to three or more antibiotics belonging to different families. 185
isolates (29.1%) were susceptible to all 13 of the antibiotics tested. The
antibiotic-susceptible isolates were further tested for possible virulence genes
and the production of biogenic amines. Finally, five enterococci isolates were
found to be antibiotic susceptible with good technological characteristics and
without virulence traits or the ability to produce biogenic amines, making them
possible candidates for biotechnological application as starter cultures in the
dairy industry.
PMID- 26441889
TI - Direct sequencing of human gut virome fractions obtained by flow cytometry.
AB - The sequence assembly of the human gut virome encounters several difficulties. A
high proportion of human and bacterial matches is detected in purified viral
samples. Viral DNA extraction results in a low DNA concentration, which does not
reach the minimal limit required for sequencing library preparation. Therefore,
the viromes are usually enriched by whole genome amplification (WGA), which is,
however, prone to the development of chimeras and amplification bias. In
addition, as there is a very wide diversity of gut viral species, very extensive
sequencing efforts must be made for the assembling of whole viral genomes. We
present an approach to improve human gut virome assembly by employing a more
precise preparation of a viral sample before sequencing. Particles present in a
virome previously filtered through 0.2 MUm pores were further divided into groups
in accordance with their size and DNA content by fluorescence activated cell
sorting (FACS). One selected viral fraction was sequenced excluding the WGA step,
so that unbiased sequences with high reliability were obtained. The DNA extracted
from the 314 viral particles of the selected fraction was assembled into 34
contigs longer than 1,000 bp. This represents an increase to the number of
assembled long contigs per sequenced Gb in comparison with other studies where
non-fractioned viromes are sequenced. Seven of these contigs contained open
reading frames (ORFs) with explicit matches to proteins related to
bacteriophages. The remaining contigs also possessed uncharacterized ORFs with
bacteriophage-related domains. When the particles that are present in the
filtered viromes are sorted into smaller groups by FACS, large pieces of viral
genomes can be recovered easily. This approach has several advantages over the
conventional sequencing of non-fractioned viromes: non-viral contamination is
reduced and the sequencing efforts required for viral assembly are minimized.
PMID- 26441891
TI - A water-forming NADH oxidase from Lactobacillus pentosus suitable for the
regeneration of synthetic biomimetic cofactors.
AB - The cell-free biocatalytic production of fine chemicals by oxidoreductases has
continuously grown over the past years. Since especially dehydrogenases depend on
the stoichiometric use of nicotinamide pyridine cofactors, an integrated
efficient recycling system is crucial to allow process operation under economic
conditions. Lately, the variety of cofactors for biocatalysis was broadened by
the utilization of totally synthetic and cheap biomimetics. Though, to date the
regeneration has been limited to chemical or electrochemical methods. Here, we
report an enzymatic recycling by the flavoprotein NADH-oxidase from Lactobacillus
pentosus (LpNox). Since this enzyme has not been described before, we first
characterized it in regard to its optimal reaction parameters. We found that the
heterologously overexpressed enzyme only contained 13% FAD. In vitro loading of
the enzyme with FAD, resulted in a higher specific activity towards its natural
cofactor NADH as well as different nicotinamide derived biomimetics. Apart from
the enzymatic recycling, which gives water as a by-product by transferring four
electrons onto oxygen, unbound FAD can also catalyze the oxidation of biomimetic
cofactors. Here a two electron process takes place yielding H2O2 instead. The
enzymatic and chemical recycling was compared in regard to reaction kinetics for
the natural and biomimetic cofactors. With LpNox and FAD, two recycling
strategies for biomimetic cofactors are described with either water or hydrogen
peroxide as by-product.
PMID- 26441890
TI - Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA
perspective.
AB - Yersinia pestis, responsible for causing fulminant plague, has evolved clonally
from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a
relatively benign enteric illness. An ~97% nucleotide identity over 75% of their
shared protein coding genes is maintained between these two pathogens, leaving
much conjecture regarding the molecular determinants responsible for producing
these vastly different disease etiologies, host preferences and transmission
routes. One idea is that coordinated production of distinct factors required for
host adaptation and virulence in response to specific environmental cues could
contribute to the distinct pathogenicity distinguishing these two species. Small
non-coding RNAs that direct posttranscriptional regulation have recently been
identified as key molecules that may provide such timeous expression of
appropriate disease enabling factors. Here the burgeoning field of small non
coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of
adaptive colonization, virulence and divergent evolution of these pathogens.
PMID- 26441892
TI - Model-driven discovery of synergistic inhibitors against E. coli and S. enterica
serovar Typhimurium targeting a novel synthetic lethal pair, aldA and prpC.
AB - Mathematical models of biochemical networks form a cornerstone of bacterial
systems biology. Inconsistencies between simulation output and experimental data
point to gaps in knowledge about the fundamental biology of the organism. One
such inconsistency centers on the gene aldA in Escherichia coli: it is essential
in a computational model of E. coli metabolism, but experimentally it is not.
Here, we reconcile this disparity by providing evidence that aldA and prpC form a
synthetic lethal pair, as the double knockout could only be created through
complementation with a plasmid-borne copy of aldA. Moreover, virtual and
biological screening against the two proteins led to a set of compounds that
inhibited the growth of E. coli and Salmonella enterica serovar Typhimurium
synergistically at 100-200 MUM individual concentrations. These results highlight
the power of metabolic models to drive basic biological discovery and their
potential use to discover new combination antibiotics.
PMID- 26441893
TI - Isolation, characterization, and complete genome analysis of P1312, a
thermostable bacteriophage that infects Thermobifida fusca.
AB - Thermobifida fusca is a moderately thermophilic and cellulolytic actinobacterium.
It is of particular interest due to its ability to not only produce a variety of
biotechnologically relevant enzymes but also serve as an alternative host for
metabolic engineering for the production of valuable chemicals from
lignocellulosic agricultural wastes. No bacteriophage that infects T. fusca has
been reported, despite its potential impacts on the utilization of T. fusca. In
this study, an extremely thermostable bacteriophage P1312 that infects T. fusca
was isolated from manure compost. Electron microscopy showed that P1312 has an
icosahedral head and a long flexible non-contractile tail, a characteristic of
the family Siphoviridae. P1312 has a double-stranded DNA genome of 60,284 bp with
93 potential ORFs. Thirty-one ORFs encode proteins having putative biological
functions. The genes involved in phage particle formation cluster together in a
region of approximately 16 kb, followed by a segment containing genes presumably
for DNA degradation/modification and cell wall disruption. The genes required for
DNA replication and transcriptional control are dispersed within the rest of the
genome. Phylogenetic analysis of large terminase subunit suggests that P1312 is a
headful packaging phage containing a chromosome with circularly permuted direct
terminal repeats.
PMID- 26441894
TI - Spatial and temporal dynamics of virus occurrence in two freshwater lakes
captured through metagenomic analysis.
AB - Viruses are the most abundant microorganisms in the aquatic environment, yet the
identification of viruses and assessing their diversity still remains a
challenge. Here, we present a robust, routinely usable approach to identify
viruses from two freshwater lakes of the lower Great Lakes region, Lake Ontario,
and Lake Erie. We collected water samples from six different beaches of these two
lakes during the summer period of 2012 and 2013, and separated into three
distinct fractions, namely a bacterial fraction, a virus like particle (VLP)
fraction, and a fraction of eDNA (environmental DNA). DNA extracted from all
three fractions was sequenced and bioinformatic analyses of sequences revealed
the presence of viruses from major viral families. The analyzed viral sequences
were dominated by bacteriophage sequences, but also contained many plant and
animal viruses. Within the context of this study, geographic location does not
appear to have a major impact on viral abundance and diversity, since virome
composition of both lakes were similar. Comparative analyses between eDNA and
viral fractions showed that eDNA can be used in combination with VLP fractions to
identify viruses from the environment.
PMID- 26441895
TI - pH-driven shifts in overall and transcriptionally active denitrifiers control
gaseous product stoichiometry in growth experiments with extracted bacteria from
soil.
AB - Soil pH is a strong regulator for activity as well as for size and composition of
denitrifier communities. Low pH not only lowers overall denitrification rates but
also influences denitrification kinetics and gaseous product stoichiometry. N2O
reductase is particularly sensitive to low pH which seems to impair its activity
post-transcriptionally, leading to higher net N2O production. Little is known
about how complex soil denitrifier communities respond to pH change and whether
their ability to maintain denitrification over a wider pH range relies on
phenotypic redundancy. In the present study, we followed the abundance and
composition of an overall and transcriptionally active denitrifier community
extracted from a farmed organic soil in Sweden (pH H2O = 7.1) when exposed to pH
5.4 and drifting back to pH 6.6. The soil was previously shown to retain much of
its functioning (low N2O/N2 ratios) over a wide pH range, suggesting a high
functional versatility of the underlying community. We found that denitrifier
community composition, abundance and transcription changed throughout incubation
concomitant with pH change in the medium, allowing for complete reduction of
nitrate to N2 with little accumulation of intermediates. When exposed to pH 5.4,
the denitrifier community was able to grow but reduced N2O to N2 only when near
neutral pH was reestablished by the alkalizing metabolic activity of an acid
tolerant part of the community. The genotypes proliferating under these
conditions differed from those dominant in the control experiment run at neutral
pH. Denitrifiers of the nirS-type appeared to be severely suppressed by low pH
and nirK-type and nosZ-containing denitrifiers showed strongly reduced
transcriptional activity and growth, even after restoration of neutral pH. Our
study suggests that low pH episodes alter transcriptionally active populations
which shape denitrifier communities and determine their gas kinetics.
PMID- 26441896
TI - Identification of natural inhibitors of Entamoeba histolytica cysteine synthase
from microbial secondary metabolites.
AB - Amebiasis is a common worldwide diarrheal disease, caused by the protozoan
parasite, Entamoeba histolytica. Metronidazole has been a drug of choice against
amebiasis for decades despite its known side effects and low efficacy against
asymptomatic cyst carriers. E. histolytica is also capable of surviving sub
therapeutic levels of metronidazole in vitro. Novel drugs with different mode of
action are therefore urgently needed. The sulfur assimilatory de novo L-cysteine
biosynthetic pathway is essential for various cellular activities, including the
proliferation and anti-oxidative defense of E. histolytica. Since the pathway,
consisting of two reactions catalyzed by serine acetyltransferase (SAT) and
cysteine synthase (CS, O-acetylserine sulfhydrylase), does not exist in humans,
it is a rational drug target against amebiasis. To discover inhibitors against
the CS of E. histolytica (EhCS), the compounds of Kitasato Natural Products
Library were screened against two recombinant CS isozymes: EhCS1 and EhCS3. Nine
compounds inhibited EhCS1 and EhCS3 with IC50 values of 0.31-490 MUM. Of those,
seven compounds share a naphthoquinone moiety, indicating the structural
importance of the moiety for binding to the active site of EhCS1 and EhCS3. We
further screened >9,000 microbial broths for CS inhibition and purified two
compounds, xanthofulvin and exophillic acid from fungal broths. Xanthofulvin
inhibited EhCS1 and EhCS3. Exophillic acid showed high selectivity against EhCS1,
but exhibited no inhibition against EhCS3. In vitro anti-amebic activity of the
11 EhCS inhibitors was also examined. Deacetylkinamycin C and nanaomycin A showed
more potent amebicidal activity with IC50 values of 18 and 0.8 MUM, respectively,
in the cysteine deprived conditions. The differential sensitivity of trophozoites
against deacetylkinamycin C in the presence or absence of L-cysteine in the
medium and the IC50 values against EhCS suggest the amebicidal effect of
deacetylkinamycin C is due to CS inhibition.
PMID- 26441897
TI - Pseudomonas Exotoxin A: optimized by evolution for effective killing.
AB - Pseudomonas Exotoxin A (PE) is the most toxic virulence factor of the pathogenic
bacterium Pseudomonas aeruginosa. This review describes current knowledge about
the intoxication pathways of PE. Moreover, PE represents a remarkable example for
pathoadaptive evolution, how bacterial molecules have been structurally and
functionally optimized under evolutionary pressure to effectively impair and kill
their host cells.
PMID- 26441898
TI - IncF plasmid diversity in multi-drug resistant Escherichia coli strains from
animals in China.
AB - The purpose of this study was to characterize a collection of 103 multidrug
resistance IncF plasmids recovered from Escherichia coli of food producing and
companion animals between 2003 and 2012. A total of 103 incF plasmids were
characterized using an established PCR-based IncF replicon sequence typing (RST)
system to identify FII, FIA, and FIB (FAB) groups. Plasmids were also analyzed
using-restriction fragment length polymorphism (RFLP). Antibiotic Resistance
determinants bla CTX-M , plasmid-mediated quinolone resistance (PMQR) genes and
rmtB and plasmid addiction systems (PAS) were identified by PCR screening. A
total of 20 different RSTs from 103 IncF plasmids were identified. The groups F2
and F33 with the RST formulae A-: B- were the most frequently encountered types
(63.1%). The antibiotic resistance genes (ARGs) bla CTX-M , rmtB, and oqxB were
carried by 82, 37, and 34 IncF plasmids, respectively. Most of these plasmids
carried more than one resistance gene (59.2%, 61/103). The IncF plasmids also had
a high frequency of addiction systems (mean 2.54) and two antisense RNA-regulated
systems (hok-sok and srnBC) and a protein antitoxin-regulated system (pemKI) were
the most prevalent. Not surprisingly, RFLP profiles among the IncF plasmids were
diverse even though some shared identical IncF-RSTs. This is the first extensive
study of IncF plasmid-positive E. coli isolates from animals in China. Our
results demonstrate that IncF is the most prevalent plasmid family in E. coli
plasmids and they commonly carry multiple resistance determinants that render
them resistant to different antibiotic classes simultaneously. IncF plasmids also
harbor addiction systems, promoting their stability and maintenance in the
bacterial host, under changing environmental conditions.
PMID- 26441899
TI - Malaria vaccines: identifying Plasmodium falciparum liver-stage targets.
AB - The development of a highly efficacious and durable vaccine for malaria remains a
top priority for global health researchers. Despite the huge rise in recognition
of malaria as a global health problem and the concurrent rise in funding over the
past 10-15 years, malaria continues to remain a widespread burden. The evidence
of increasing resistance to anti-malarial drugs and insecticides is a growing
concern. Hence, an efficacious and durable preventative vaccine for malaria is
urgently needed. Vaccines are one of the most cost-effective tools and have
successfully been used in the prevention and control of many diseases, however,
the development of a vaccine for the Plasmodium parasite has proved difficult.
Given the early success of whole sporozoite mosquito-bite delivered vaccination
strategies, we know that a vaccine for malaria is an achievable goal, with sub
unit vaccines holding great promise as they are simple and cheap to both
manufacture and deploy. However a major difficulty in development of sub-unit
vaccines lies within choosing the appropriate antigenic target from the 5000 or
so genes expressed by the parasite. Given the liver-stage of malaria represents a
bottle-neck in the parasite's life cycle, there is widespread agreement that a
multi-component sub-unit malaria vaccine should preferably contain a liver-stage
target. In this article we review progress in identifying and screening
Plasmodium falciparum liver-stage targets for use in a malaria vaccine.
PMID- 26441900
TI - Metagenomic analysis reveals that modern microbialites and polar microbial mats
have similar taxonomic and functional potential.
AB - Within the subarctic climate of Clinton Creek, Yukon, Canada, lies an abandoned
and flooded open-pit asbestos mine that harbors rapidly growing microbialites. To
understand their formation we completed a metagenomic community profile of the
microbialites and their surrounding sediments. Assembled metagenomic data
revealed that bacteria within the phylum Proteobacteria numerically dominated
this system, although the relative abundances of taxa within the phylum varied
among environments. Bacteria belonging to Alphaproteobacteria and
Gammaproteobacteria were dominant in the microbialites and sediments,
respectively. The microbialites were also home to many other groups associated
with microbialite formation including filamentous cyanobacteria and dissimilatory
sulfate-reducing Deltaproteobacteria, consistent with the idea of a shared global
microbialite microbiome. Other members were present that are typically not
associated with microbialites including Gemmatimonadetes and iron-oxidizing
Betaproteobacteria, which participate in carbon metabolism and iron cycling.
Compared to the sediments, the microbialite microbiome has significantly more
genes associated with photosynthetic processes (e.g., photosystem II reaction
centers, carotenoid, and chlorophyll biosynthesis) and carbon fixation (e.g., CO
dehydrogenase). The Clinton Creek microbialite communities had strikingly similar
functional potentials to non-lithifying microbial mats from the Canadian High
Arctic and Antarctica, but are functionally distinct, from non-lithifying mats or
biofilms from Yellowstone. Clinton Creek microbialites also share metabolic genes
(R (2) < 0.750) with freshwater microbial mats from Cuatro Cienegas, Mexico, but
are more similar to polar Arctic mats (R (2) > 0.900). These metagenomic profiles
from an anthropogenic microbialite-forming ecosystem provide context to
microbialite formation on a human-relevant timescale.
PMID- 26441901
TI - Biogeography and evolution of Thermococcus isolates from hydrothermal vent
systems of the Pacific.
AB - Thermococcus is a genus of hyperthermophilic archaea that is ubiquitous in marine
hydrothermal environments growing in anaerobic subsurface habitats but able to
survive in cold oxygenated seawater. DNA analyses of Thermococcus isolates were
applied to determine the relationship between geographic distribution and
relatedness focusing primarily on isolates from the Juan de Fuca Ridge and South
East Pacific Rise. Amplified fragment length polymorphism (AFLP) analysis and
multilocus sequence typing (MLST) were used to resolve genomic differences in 90
isolates of Thermococcus, making biogeographic patterns and evolutionary
relationships apparent. Isolates were differentiated into regionally endemic
populations however there was also evidence in some lineages of cosmopolitan
distribution. The biodiversity identified in Thermococcus isolates and presence
of distinct lineages within the same vent site suggests the utilization of
varying ecological niches in this genus. In addition to resolving biogeographic
patterns in Thermococcus, this study has raised new questions about the closely
related Pyrococcus genus. The phylogenetic placement of Pyrococcus type strains
shows the close relationship between Thermococcus and Pyrococcus and the
unresolved divergence of these two genera.
PMID- 26441902
TI - Attributes of carbapenemase encoding conjugative plasmid pNDM-SAL from an
extensively drug-resistant Salmonella enterica Serovar Senftenberg.
AB - A carbapenem resistant Salmonella enterica serovar Senftenberg isolate BCH 2406
was isolated from a diarrheal child attending an outpatient unit of B.C. Roy
Hospital in Kolkata, India. This isolate was positive for the bla NDM-1 in the
PCR assay, which was confirmed by amplicon sequencing. Except for tetracycline,
this isolate was resistant to all the tested antimicrobials. The bla NDM-1 was
found to be located on a 146.13-kb mega plasmid pNDM-SAL, which could be
conjugally transferred into Escherichia coli and other enteric pathogens such as
Vibrio cholerae O1 Ogawa and Shigella flexneri 2a. However, the expression of
beta-lactam resistance is not the same in different bacteria. The whole genome
sequence of pNDM-SAL was determined and compared with other pNDM plasmids
available in public domain. This plasmid is an IncA/C incompatibility type
composed of 155 predicted coding sequences and shares homology with plasmids of
E. coli pNDM-1_Dok01, Klebsiella pNDM-KN, and Citrobacter pNDM-CIT. In pNDM-SAL,
gene cluster containing bla NDM-1 was located between IS26 and IS4321 elements.
Between the IS26 element and the bla NDM-1, a truncated ISAba125 insertion
sequence was identified. Downstream of the bla NDM-1, other genes, such as ble
MBL, trpF, tat, and an ISCR1 element with class 1 integron containing aac(6')-Ib
were detected. Another beta-lactacamase gene, bla CMY -4 was found to be inserted
in IS1 element within the type IV conjugative transfer loci of the plasmid. This
gene cluster had blc and sugE downstream of the bla CMY -4. From our findings, it
appears that the strain S. Senftenberg could have acquired the NDM plasmid from
the other members of Enterobacteriaceae. Transfer of NDM plasmids poses a danger
in the management of infectious diseases.
PMID- 26441903
TI - French invasive Asian tiger mosquito populations harbor reduced bacterial
microbiota and genetic diversity compared to Vietnamese autochthonous relatives.
AB - The Asian tiger mosquito Aedes albopictus is one of the most significant pathogen
vectors of the twenty-first century. Originating from Asia, it has invaded a wide
range of eco-climatic regions worldwide. The insect-associated microbiota is now
recognized to play a significant role in host biology. While genetic diversity
bottlenecks are known to result from biological invasions, the resulting shifts
in host-associated microbiota diversity has not been thoroughly investigated. To
address this subject, we compared four autochthonous Ae. albopictus populations
in Vietnam, the native area of Ae. albopictus, and three populations recently
introduced to Metropolitan France, with the aim of documenting whether these
populations display differences in host genotype and bacterial microbiota.
Population-level genetic diversity (microsatellite markers and COI haplotype) and
bacterial diversity (16S rDNA metabarcoding) were compared between field-caught
mosquitoes. Bacterial microbiota from the whole insect bodies were largely
dominated by Wolbachia pipientis. Targeted analysis of the gut microbiota
revealed a greater bacterial diversity in which a fraction was common between
French and Vietnamese populations. The genus Dysgonomonas was the most prevalent
and abundant across all studied populations. Overall genetic diversities of both
hosts and bacterial microbiota were significantly reduced in recently established
populations of France compared to the autochthonous populations of Vietnam. These
results open up many important avenues of investigation in order to link the
process of geographical invasion to shifts in commensal and symbiotic microbiome
communities, as such shifts may have dramatic impacts on the biology and/or
vector competence of invading hematophagous insects.
PMID- 26441904
TI - The diversity of the N2O reducers matters for the N2O:N2 denitrification end
product ratio across an annual and a perennial cropping system.
AB - Agriculture is the main source of terrestrial emissions of N2O, a potent
greenhouse gas and the main cause of ozone layer depletion. The reduction of N2O
into N2 by microorganisms carrying the nitrous oxide reductase gene (nosZ) is the
only biological process known to eliminate this greenhouse gas. Recent studies
showed that a previously unknown clade of N2O-reducers was related to the
capacity of the soil to act as an N2O sink, opening the way for new strategies to
mitigate emissions. Here, we investigated whether the agricultural practices
could differently influence the two N2O reducer clades with consequences for
denitrification end-products. The abundance of N2O-reducers and producers was
quantified by real-time PCR, and the diversity of both nosZ clades was determined
by 454 pyrosequencing. Potential N2O production and potential denitrification
activity were used to calculate the denitrification gaseous end-product ratio.
Overall, the results showed limited differences between management practices but
there were significant differences between cropping systems in both the abundance
and structure of the nosZII community, as well as in the [rN2O/r(N2O+N2)] ratio.
More limited differences were observed in the nosZI community, suggesting that
the newly identified nosZII clade is more sensitive than nosZI to environmental
changes. Potential denitrification activity and potential N2O production were
explained mainly by the soil properties while the diversity of the nosZII clade
on its own explained 26% of the denitrification end-product ratio, which
highlights the importance of understanding the ecology of this newly identified
clade of N2O reducers for mitigation strategies.
PMID- 26441905
TI - Efficient recombinant production of prodigiosin in Pseudomonas putida.
AB - Serratia marcescens and several other bacteria produce the red-colored pigment
prodigiosin which possesses bioactivities as an antimicrobial, anticancer, and
immunosuppressive agent. Therefore, there is a great interest to produce this
natural compound. Efforts aiming at its biotechnological production have so far
largely focused on the original producer and opportunistic human pathogen S.
marcescens. Here, we demonstrate efficient prodigiosin production in the
heterologous host Pseudomonas putida. Random chromosomal integration of the 21 kb
prodigiosin biosynthesis gene cluster of S. marcescens in P. putida KT2440 was
employed to construct constitutive prodigiosin production strains. Standard
cultivation parameters were optimized such that titers of 94 mg/L culture were
obtained upon growth of P. putida at 20 degrees C using rich medium under high
aeration conditions. Subsequently, a novel, fast and effective protocol for
prodigiosin extraction and purification was established enabling the
straightforward isolation of prodigiosin from P. putida growth medium. In
summary, we describe here a highly efficient method for the heterologous
biosynthetic production of prodigiosin which may serve as a basis to produce
large amounts of this bioactive natural compound and may provide a platform for
further in-depth studies of prodiginine biosynthesis.
PMID- 26441906
TI - Oleylphosphocholine (OlPC) arrests Cryptosporidium parvum growth in vitro and
prevents lethal infection in interferon gamma receptor knock-out mice.
AB - Cryptosporidium parvum is a species of protozoa that causes cryptosporidiosis, an
intestinal disease affecting many mammals including humans. Typically, in healthy
individuals, cryptosporidiosis is a self-limiting disease. However, C. parvum can
cause a severe and persistent infection that can be life-threatening for
immunocompromised individuals, such as AIDS patients. As there are no available
treatments for these patients that can cure the disease, there is an urgent need
to identify treatment options. We tested the anti-parasitic activity of the
alkylphosphocholine oleylphosphocholine (OlPC), an analog of miltefosine, against
C. parvum in in vitro and in vivo studies. In vitro experiments using C. parvum
infected human ileocecal adenocarcinoma cells (HCT-8 cells) showed that OlPC has
an EC50 of 18.84 nM. Moreover, no cell toxicity has been seen at concentrations
<=50 MUM. C57BL/6 interferon gamma receptor knock-out mice, were infected by
gavage with 4000 C. parvum oocysts on Day 0. Oral treatments, with OlPC,
miltefosine, paromomycin or PBS, began on Day 3 post-infection for 10 days.
Treatment with OlPC, at 40 mg/kg/day resulted in 100% survival, complete
clearance of parasite in stools and a 99.9% parasite burden reduction in the
intestines at Day 30. Doses of 30 and 20 mg/kg/day also demonstrated an increased
survival rate and a dose-dependent parasite burden reduction. Mice treated with
10 mg/kg/day of miltefosine resulted in 50% survival at Day 30. In contrast,
control mice, treated with PBS or 100 mg/kg/day of paromomycin, died or had to be
euthanized between Days 6 and 13 due to severe illness. Results of parasite
burden were obtained by qPCR and cross-validated by both flow cytometry of stool
oocysts and histological sections of the ileum. Together, our results strongly
support that OlPC represents a potential candidate for the treatment of C. parvum
infections in immunocompromised patients.
PMID- 26441907
TI - Corrigendum: Vesicles-mediated resistance to antibiotics in bacteria.
AB - [This corrects the article on p. 758 in vol. 6, PMID: 26257725.].
PMID- 26441908
TI - Optimization and characterization of biosurfactant production from marine Vibrio
sp. strain 3B-2.
AB - A biosurfactant-producing bacterium, designated 3B-2, was isolated from marine
sediment and identified as Vibrio sp. by 16S rRNA gene sequencing. The culture
medium composition was optimized to increase the capability of 3B-2 for producing
biosurfactant. The produced biosurfactant was characterized in terms of protein
concentration, surface tension, and oil-displacement efficiency. The optimal
medium for biosurfactant production contained: 0.5% lactose, 1.1% yeast extract,
2% sodium chloride, and 0.1% disodium hydrogen phosphate. Under optimal
conditions (28 degrees C), the surface tension of crude biosurfactant could be
reduced to 41 from 71.5 mN/m (water), while its protein concentration was
increased to up to 6.5 g/L and the oil displacement efficiency was improved
dramatically at 6.5 cm. Two glycoprotein fractions with the molecular masses of
22 and 40 kDa were purified from the biosurfactant, which held great potential
for applications in microbial enhanced oil recovery and bioremediation.
PMID- 26441909
TI - Genome sequence of the plant growth promoting endophytic yeast Rhodotorula
graminis WP1.
PMID- 26441910
TI - Insights on virulence from the complete genome of Staphylococcus capitis.
AB - Staphylococcus capitis is an opportunistic pathogen of the coagulase negative
staphylococci (CoNS). Functional genomic studies of S. capitis have thus far been
limited by a lack of available complete genome sequences. Here, we determined the
closed S. capitis genome and methylome using Single Molecule Real Time (SMRT)
sequencing. The strain, AYP1020, harbors a single circular chromosome of 2.44 Mb
encoding 2304 predicted proteins, which is the smallest of all complete
staphylococcal genomes sequenced to date. AYP1020 harbors two large mobile
genetic elements; a plasmid designated pAYP1020 (59.6 Kb) and a prophage,
PhiAYP1020 (48.5 Kb). Methylome analysis identified significant adenine
methylation across the genome involving two distinct methylation motifs (1972
putative 6-methyladenine (m6A) residues identified). Putative adenine
methyltransferases were also identified. Comparative analysis of AYP1020 and the
closely related CoNS, S. epidermidis RP62a, revealed a host of virulence factors
that likely contribute to S. capitis pathogenicity, most notably genes important
for biofilm formation and a suite of phenol soluble modulins (PSMs); the
expression/production of these factors were corroborated by functional assays.
The complete S. capitis genome will aid future studies on the evolution and
pathogenesis of the coagulase negative staphylococci.
PMID- 26441911
TI - Application of tea polyphenols in combination with 6-gingerol on shrimp paste of
during storage: biogenic amines formation and quality determination.
AB - Tea polyphenols (TP) have shown antioxidant activity and antimicrobial properties
in the food industry. Assessment of anti-oxidation potential of 6-gingerol (GR)
has also been verified. As little is known about the use of tea polyphenols
either individually or in combination with 6-gingerol in shrimp paste, we aimed
to investigate the effect of tea polyphenols combined with 6-gingerol on the
biogenic amines inhibition and quality of shrimp paste stored at 25 degrees C for
160 days. The shrimp paste samples were assigned into four groups: (1) control;
(2) tea polyphenols treatment (0.3%); (3) 6-gingerol treatment (0.3%); (4) tea
polyphenols (0.15%) + 6-gingerol (0.15%). Samples with no addition were used as
control. The results indicate that treatment with tea polyphenols + 6-gingerol
(TPGR) maintained paste appearance, inhibited oxidation of protein and lipids,
and reduced microorganism counts compared to control treatment. The efficiency
was superior to that of tea polyphenols or 6-gingerol treatment. Furthermore,
shrimp paste treated with TPGR also exhibited significantly higher inhibition of
biogenic amines. Total amino acids determination proved the efficacy of TPGR by
maintaining the more amino acids of shrimp paste during ambient temperature
storage. Our study suggests that TPGR might be a promising candidate for
fermented foods due to its synergistic effect to maintain products quality and
extending their shelf-life.
PMID- 26441912
TI - Fungal endophyte Phomopsis liquidambari affects nitrogen transformation processes
and related microorganisms in the rice rhizosphere.
AB - The endophytic fungus Phomopsis liquidambari performs an important ecosystem
service by assisting its host with acquiring soil nitrogen (N), but little is
known regarding how this fungus influences soil N nutrient properties and
microbial communities. In this study, we investigated the impact of P.
liquidambari on N dynamics, the abundance and composition of N cycling genes in
rhizosphere soil treated with three levels of N (urea). Ammonia-oxidizing archaea
(AOA), ammonia-oxidizing bacteria (AOB) and diazotrophs were assayed using
quantitative real-time polymerase chain reaction and denaturing gradient gel
electrophoresis at four rice growing stages (S0: before planting, S1: tillering
stage, S2: grain filling stage, and S3: ripening stage). A significant increase
in the available nitrate and ammonium contents was found in the rhizosphere soil
of endophyte-infected rice under low N conditions. Moreover, P. liquidambari
significantly increased the potential nitrification rates, affected the abundance
and community structure of AOA, AOB, and diazotrophs under low N conditions in
the S1 and S2 stages. The root exudates were determined due to their important
role in rhizosphere interactions. P. liquidambari colonization altered the
exudation of organic compounds by rice roots and P. liquidambari increased the
concentration of soluble saccharides, total free amino acids and organic acids in
root exudates. Plant-soil feedback mechanisms may be mediated by the rice
endophyte interaction, especially in nutrient-limited soil.
PMID- 26441913
TI - A new wine Torulaspora delbrueckii killer strain with broad antifungal activity
and its toxin-encoding double-stranded RNA virus.
AB - Wine Torulaspora delbrueckii strains producing a new killer toxin (Kbarr-1) were
isolated and selected for wine making. They killed all the previously known
Saccharomyces cerevisiae killer strains, in addition to other non-Saccharomyces
yeasts. The Kbarr-1 phenotype is encoded by a medium-size 1.7 kb dsRNA, TdV-Mbarr
1, which seems to depend on a large-size 4.6 kb dsRNA virus (TdV-LAbarr) for
stable maintenance and replication. The TdV-Mbarr-1 dsRNA was sequenced by new
generation sequencing techniques. Its genome structure is similar to those of S.
cerevisiae killer M dsRNAs, with a 5'-end coding region followed by an internal A
rich sequence and a 3'-end non-coding region. Mbarr-1 RNA positive strand carries
cis acting signals at its 5' and 3' termini for transcription and replication
respectively, similar to those RNAs of yeast killer viruses. The ORF at the 5'
region codes for a putative preprotoxin with an N-terminal secretion signal,
potential Kex2p/Kexlp processing sites, and N-glycosylation sites. No relevant
sequence identity was found either between the full sequence of Mbarr-1 dsRNA and
other yeast M dsRNAs, or between their respective toxin-encoded proteins.
However, a relevant identity of TdV-Mbarr-1 RNA regions to the putative
replication and packaging signals of most of the M-virus RNAs suggests that they
are all evolutionarily related.
PMID- 26441914
TI - Salmonella Typhimurium exploits inflammation to its own advantage in piglets.
AB - Salmonella Typhimurium (S. Typhimurium) is responsible for foodborne zoonotic
infections that, in humans, induce self-limiting gastroenteritis. The aim of this
study was to evaluate whether the wild-type strain S. Typhimurium (STM14028) is
able to exploit inflammation fostering an active infection. Due to the similarity
between human and porcine diseases induced by S. Typhimurium, we used piglets as
a model for salmonellosis and gastrointestinal research. This study showed that
STM14028 is able to efficiently colonize in vitro porcine mono-macrophages and
intestinal columnar epithelial (IPEC-J2) cells, and that the colonization
significantly increases with LPS pre-treatment. This increase was then reversed
by inhibiting the LPS stimulation through LPS antagonist, confirming an active
role of LPS stimulation in STM14028-intracellular colonization. Moreover, LPS in
vivo treatment increased cytokines blood level and body temperature at 4 h post
infection, which is consistent with an acute inflammatory stimulus, capable to
influence the colonization of STM14028 in different organs and tissues. The
present study proves for the first time that in acute enteric salmonellosis, S.
Typhimurium exploits inflammation for its benefit in piglets.
PMID- 26441915
TI - Insights into arsenic multi-operons expression and resistance mechanisms in
Rhodopseudomonas palustris CGA009.
AB - Arsenic (As) is widespread in the environment and causes numerous health
problems. Rhodopseudomonas palustris has been regarded as a good model organism
for studying arsenic detoxification since it was first demonstrated to methylate
environmental arsenic by conversion to soluble or gaseous methylated species.
However, the detailed arsenic resistance mechanisms remain unknown though there
are at least three arsenic-resistance operons (ars1, ars2, and ars3) in R.
palustris. In this study, we investigated how arsenic multi-operons contributed
to arsenic detoxification in R. palustris. The expression of ars2 or ars3 operons
increased with increasing environmental arsenite (As(III)) concentrations (up to
1.0 mM) while transcript of ars1 operon was not detected in the middle log-phase
(55 h). ars2 operon was actively expressed even at the low concentration of
As(III) (0.01 MUM), whereas the ars3 operon was expressed at 1.0 MUM of As(III),
indicating that there was a differential regulation mechanism for the three
arsenic operons. Furthermore, ars2 and ars3 operons were maximally transcribed in
the early log-phase where ars2 operon was 5.4-fold higher than that of ars3
operon. A low level of ars1 transcript was only detected at 43 h (early log
phase). Arsenic speciation analysis demonstrated that R. palustris could reduce
As(V) to As(III). Collectively, strain CGA009 detoxified arsenic by using arsenic
reduction and methylating arsenic mechanism, while the latter might occur with
the presence of higher concentrations of arsenic.
PMID- 26441916
TI - Physiological and genomic characterization of Arcobacter anaerophilus IR-1
reveals new metabolic features in Epsilonproteobacteria.
AB - In this study we characterized and sequenced the genome of Arcobacter
anaerophilus strain IR-1 isolated from enrichment cultures used in nitrate
amended corrosion experiments. A. anaerophilus IR-1 could grow
lithoautotrophically on hydrogen and hydrogen sulfide and lithoheterothrophically
on thiosulfate and elemental sulfur. In addition, the strain grew
organoheterotrophically on yeast extract, peptone, and various organic acids. We
show for the first time that Arcobacter could grow on the complex organic
substrate tryptone and oxidize acetate with elemental sulfur as electron
acceptor. Electron acceptors utilized by most Epsilonproteobacteria, such as
oxygen, nitrate, and sulfur, were also used by A. anaerophilus IR-1. Strain IR-1
was also uniquely able to use iron citrate as electron acceptor. Comparative
genomics of the Arcobacter strains A. butzleri RM4018, A. nitrofigilis CI and A.
anaerophilus IR-1 revealed that the free-living strains had a wider metabolic
range and more genes in common compared to the pathogen strain. The presence of
genes for NAD(+)-reducing hydrogenase (hox) and dissimilatory iron reduction
(fre) were unique for A. anaerophilus IR-1 among Epsilonproteobacteria. Finally,
the new strain had an incomplete denitrification pathway where the end product
was nitrite, which is different from other Arcobacter strains where the end
product is ammonia. Altogether, our study shows that traditional characterization
in combination with a modern genomics approach can expand our knowledge on free
living Arcobacter, and that this complementary approach could also provide
invaluable knowledge about the physiology and metabolic pathways in other
Epsilonproteobacteria from various environments.
PMID- 26441917
TI - Growth and activity of ANME clades with different sulfate and sulfide
concentrations in the presence of methane.
AB - Extensive geochemical data showed that significant methane oxidation activity
exists in marine sediments. The organisms responsible for this activity are
anaerobic methane-oxidizing archaea (ANME) that occur in consortia with sulfate
reducing bacteria. A distinct zonation of different clades of ANME (ANME-1, ANME
2a/b, and ANME-2c) exists in marine sediments, which could be related to the
localized concentrations of methane, sulfate, and sulfide. In order to test this
hypothesis we performed long-term incubation of marine sediments under defined
conditions with methane as a headspace gas: low or high sulfate (+/-4 and +/-21
mM, respectively) in combination with low or high sulfide (+/-0.1 and +/-4 mM,
respectively) concentrations. Control incubations were also performed, with only
methane, high sulfate, or high sulfide. Methane oxidation was monitored and
growth of subtypes ANME-1, ANME-2a/b, and ANME-2c assessed using qPCR analysis. A
preliminary archaeal community analysis was performed to gain insight into the
ecological and taxonomic diversity. Almost all of the incubations with methane
had methane oxidation activity, with the exception of the incubations with
combined low sulfate and high sulfide concentrations. Sulfide inhibition occurred
only with low sulfate concentrations, which could be due to the lower Gibbs free
energy available as well as sulfide toxicity. ANME-2a/b appears to mainly grow in
incubations which had high sulfate levels and methane oxidation activity, whereas
ANME-1 did not show this distinction. ANME-2c only grew in incubations with only
sulfate addition. These findings are consistent with previously published in situ
profiling analysis of ANME subclusters in different marine sediments.
Interestingly, since all ANME subtypes also grew in incubations with only methane
or sulfate addition, ANME may also be able to perform anaerobic methane oxidation
under substrate limited conditions or alternatively perform additional metabolic
processes.
PMID- 26441918
TI - The globally widespread genus Sulfurimonas: versatile energy metabolisms and
adaptations to redox clines.
AB - Sulfurimonas species are commonly isolated from sulfidic habitats and numerous
16S rRNA sequences related to Sulfurimonas species have been identified in
chemically distinct environments, such as hydrothermal deep-sea vents, marine
sediments, the ocean's water column, and terrestrial habitats. In some of these
habitats, Sulfurimonas have been demonstrated to play an important role in
chemoautotrophic processes. Sulfurimonas species can grow with a variety of
electron donors and acceptors, which may contribute to their widespread
distribution. Multiple copies of one type of enzyme (e.g., sulfide:quinone
reductases and hydrogenases) may play a pivotal role in Sulfurimonas' flexibility
to colonize disparate environments. Many of these genes appear to have been
acquired through horizontal gene transfer which has promoted adaptations to the
distinct habitats. Here we summarize Sulfurimonas' versatile energy metabolisms
and link their physiological properties to their global distribution.
PMID- 26441919
TI - The novel cis-encoded antisense RNA AsrC positively regulates the expression of
rpoE-rseABC operon and thus enhances the motility of Salmonella enterica serovar
typhi.
AB - Bacterial non-coding RNAs are essential in many cellular processes, including
response to environmental stress, and virulence. Deep sequencing analysis of the
Salmonella enterica serovar typhi (S. typhi) transcriptome revealed a novel
antisense RNA transcribed in cis on the strand complementary to rseC, an
activator gene of sigma factor RpoE. In this study, expression of this antisense
RNA was confirmed in S. typhi by Northern hybridization. Rapid amplification of
cDNA ends and sequence analysis identified an 893 bp sequence from the antisense
RNA coding region that covered all of the rseC coding region in the reverse
direction of transcription. This sequence of RNA was named as AsrC. After
overexpression of AsrC with recombinantant plasmid in S. typhi, the bacterial
motility was increased obviously. To explore the mechanism of AsrC function,
regulation of rseC and rpoE expression by AsrC was investigated. We found that
AsrC increased the levels of rseC mRNA and protein. The expression of rpoE was
also increased in S. typhi after overexpression of AsrC, which was dependent on
rseC. Thus, we propose that AsrC increased RseC level and indirectly activating
RpoE which can initiate fliA expression and promote the motility of S. typhi.
PMID- 26441920
TI - Quantitative RT-PCR assay for high-throughput screening (HTS) of drugs against
the growth of Cryptosporidium parvum in vitro.
AB - Our laboratory has previously developed a qRT-PCR assay to assess drug efficacy
on the growth of Cryptosporidium parvum in vitro by detecting the levels of
parasite 18S rRNA. This approach displayed up to four orders of magnitude of
linear dynamic range and was much less labor-intensive than the traditional
microscopic methods. However, conventional qRT-PCR protocol is not very amendable
to high-throughput analysis when total RNA needs to be purified by lengthy, multi
step procedures. Recently, several commercial reagents are available for
preparing cell lysates that could be directly used in downstream qRT-PCR analysis
(e.g., Ambion Cell-to-cDNA kit and Bio-Rad iScript sample preparation reagent).
Using these reagents, we are able to adapt the qRT-PCR assay into high-throughput
screening of drugs in vitro (i.e., 96-well and 384-well formats for the
cultivation of parasites and qRT-PCR detection, respectively). This qRT-PCR
protocol is able to give a >150-fold linear dynamic range using samples isolated
from cells infected with various numbers of parasites. The new assay is also
validated by the NIH-recommended intra-plate, inter-plate, and inter-day
uniformity tests. The robustness and effectiveness of the assay are also
confirmed by evaluating the anti-cryptosporidial efficacy of paromomycin and by a
small scale screening of compounds.
PMID- 26441921
TI - The death mechanism of the harmful algal bloom species Alexandrium tamarense
induced by algicidal bacterium Deinococcus sp. Y35.
AB - Harmful algal blooms (HABs) cause a variety of deleterious effects on aquatic
ecosystems, especially the toxic dinoflagellate Alexandrium tamarense, which
poses a serious threat to marine economic and human health based on releasing
paralytic shellfish poison into the environment. The algicidal bacterium
Deinococcus sp. Y35 which can induce growth inhibition on A. tamarense was used
to investigate the functional mechanism. The growth status, reactive oxygen
species (ROS) content, photosynthetic system and the nuclear system of algal
cells were determined under algicidal activity. A culture of strain Y35 not only
induced overproduction of ROS in algal cells within only 0.5 h of treatment, also
decrease the total protein content as well as the response of the antioxidant
enzyme. Meanwhile, lipid peroxidation was induced and cell membrane integrity was
lost. Photosynthetic pigments including chlorophyll a and carotenoid decreased
along with the photosynthetic efficiency being significantly inhibited. At the
same time, photosynthesis-related gene expression showed down-regulation. More
than, the destruction of cell nuclear structure and inhibition of proliferating
cell nuclear antigen (PCNA) related gene expression were confirmed. The potential
functional mechanism of the algicidal bacterium on A. tamarense was investigated
and provided a novel viewpoint which could be used in HABs control.
PMID- 26441922
TI - Thiomonas sp. CB2 is able to degrade urea and promote toxic metal precipitation
in acid mine drainage waters supplemented with urea.
AB - The acid mine drainage (AMD) in Carnoules (France) is characterized by the
presence of toxic metals such as arsenic. Several bacterial strains belonging to
the Thiomonas genus, which were isolated from this AMD, are able to withstand
these conditions. Their genomes carry several genomic islands (GEIs), which are
known to be potentially advantageous in some particular ecological niches. This
study focused on the role of the "urea island" present in the Thiomonas CB2
strain, which carry the genes involved in urea degradation processes. First,
genomic comparisons showed that the genome of Thiomonas sp. CB2, which is able to
degrade urea, contains a urea genomic island which is incomplete in the genome of
other strains showing no urease activity. The urease activity of Thiomonas sp.
CB2 enabled this bacterium to maintain a neutral pH in cell cultures in vitro and
prevented the occurrence of cell death during the growth of the bacterium in a
chemically defined medium. In AMD water supplemented with urea, the degradation
of urea promotes iron, aluminum and arsenic precipitation. Our data show that
ureC was expressed in situ, which suggests that the ability to degrade urea may
be expressed in some Thiomonas strains in AMD, and that this urease activity may
contribute to their survival in contaminated environments.
PMID- 26441923
TI - Whole genome resequencing of Botrytis cinerea isolates identifies high levels of
standing diversity.
AB - How standing genetic variation within a pathogen contributes to diversity in
host/pathogen interactions is poorly understood, partly because most studied
pathogens are host-specific, clonally reproducing organisms which complicates
genetic analysis. In contrast, Botrytis cinerea is a sexually reproducing, true
haploid ascomycete that can infect a wide range of diverse plant hosts. While
previous work had shown significant genomic variation between two isolates, we
proceeded to assess the level and frequency of standing variation in a population
of B. cinerea. To begin measuring standing genetic variation in B. cinerea, we re
sequenced the genomes of 13 different isolates and aligned them to the previously
sequenced T4 reference genome. In addition one of these isolates was resequenced
from four independently repeated cultures. A high level of genetic diversity was
found within the 13 isolates. Within this variation, we could identify clusters
of genes with major effect polymorphisms, i.e., polymorphisms that lead to a
predicted functional knockout, that surrounded genes involved in controlling
vegetative incompatibility. The genotype at these loci was able to partially
predict the interaction of these isolates in vegetative fusion assays showing
that these loci control vegetative incompatibility. This suggests that the
vegetative incompatibility loci within B. cinerea are associated with regions of
increased genetic diversity. The genome re-sequencing of four clones from the one
isolate (Grape) that had been independently propagated over 10 years showed no
detectable spontaneous mutation. This suggests that B. cinerea does not display
an elevated spontaneous mutation rate. Future work will allow us to test if, and
how, this diversity may be contributing to the pathogen's broad host range.
PMID- 26441924
TI - Rapid detection of Acinetobacter baumannii and molecular epidemiology of
carbapenem-resistant A. baumannii in two comprehensive hospitals of Beijing,
China.
AB - Acinetobacter baumannii is an important opportunistic pathogen associated with a
variety of nosocomial infections. A rapid and sensitive molecular detection in
clinical isolates is quite needed for the appropriate therapy and outbreak
control of A. baumannii. Group 2 carbapenems have been considered the agents of
choice for the treatment of multiple drug-resistant A. baumannii. But the
prevalence of carbapenem-resistant A. baumannii (CRAB) has been steadily
increasing in recent years. Here, we developed a loop-mediated isothermal
amplification (LAMP) assay for the rapid detection of A. baumannii in clinical
samples by using high-specificity primers of the bla OXA-51 gene. Then we
investigated the OXA-carbapenemases molecular epidemiology of A. baumannii
isolates in two comprehensive hospitals in Beijing. The results showed that the
LAMP assay could detect target DNA within 60 min at 65 degrees C. The detection
limit was 50 pg/MUl, which was about 10-fold greater than that of PCR.
Furthermore, this method could distinguish A. baumannii from the homologous A.
nosocomialis and A. pittii. A total of 228 positive isolates were identified by
this LAMP-based method for A. baumannii from 335 intensive care unit patients
with clinically suspected multi-resistant infections in two hospitals in Beijing.
The rates of CRAB are on the rise and are slowly becoming a routine phenotype for
A. baumannii. Among the CRABs, 92.3% harbored both the bla OXA-23 and bla OXA-51
genes. Thirty-three pulsotypes were identified by pulsed-field gel
electrophoresis, and the majority belonged to clone C. In conclusion, the LAMP
method developed for detecting A. baumannii was faster and simpler than
conventional PCR and has great potential for both point-of-care testing and basic
research. We further demonstrated a high distribution of class D carbapenemase
encoding genes, mainly OXA-23, which presents an emerging threat in hospitals in
China.
PMID- 26441925
TI - Meta-omic signatures of microbial metal and nitrogen cycling in marine oxygen
minimum zones.
AB - Iron (Fe) and copper (Cu) are essential cofactors for microbial metalloenzymes,
but little is known about the metalloenyzme inventory of anaerobic marine
microbial communities despite their importance to the nitrogen cycle. We compared
dissolved O2, NO[Formula: see text], NO[Formula: see text], Fe and Cu
concentrations with nucleic acid sequences encoding Fe and Cu-binding proteins in
21 metagenomes and 9 metatranscriptomes from Eastern Tropical North and South
Pacific oxygen minimum zones and 7 metagenomes from the Bermuda Atlantic Time
series Station. Dissolved Fe concentrations increased sharply at upper oxic
anoxic transition zones, with the highest Fe:Cu molar ratio (1.8) occurring at
the anoxic core of the Eastern Tropical North Pacific oxygen minimum zone and
matching the predicted maximum ratio based on data from diverse ocean sites. The
relative abundance of genes encoding Fe-binding proteins was negatively
correlated with O2, driven by significant increases in genes encoding Fe-proteins
involved in dissimilatory nitrogen metabolisms under anoxia. Transcripts encoding
cytochrome c oxidase, the Fe- and Cu-containing terminal reductase in aerobic
respiration, were positively correlated with O2 content. A comparison of the
taxonomy of genes encoding Fe- and Cu-binding vs. bulk proteins in OMZs revealed
that Planctomycetes represented a higher percentage of Fe genes while
Thaumarchaeota represented a higher percentage of Cu genes, particularly at
oxyclines. These results are broadly consistent with higher relative abundance of
genes encoding Fe-proteins in the genome of a marine planctomycete vs. higher
relative abundance of genes encoding Cu-proteins in the genome of a marine
thaumarchaeote. These findings highlight the importance of metalloenzymes for
microbial processes in oxygen minimum zones and suggest preferential Cu use in
oxic habitats with Cu > Fe vs. preferential Fe use in anoxic niches with Fe > Cu.
PMID- 26441926
TI - Assessment of combination therapy in BALB/c mice injected with carbapenem
resistant Enterobacteriaceae strains.
AB - Monotherapeutic options for carbapenem resistant infections are limited. Studies
suggest that combination therapy may be associated with better outcomes than
monotherapies. However, this is still controversial. This study assessed, the
efficacy of combination therapy against carbapenem resistant Enterobacteriaceae
harboring singly various extended spectrum beta lactamase or carbapenemase
encoding genes. Thus, four isolates harboring either bla CTXM-15, bla CTXM-15 and
bla OXA-48, bla NDM-1, or bla KPC-2 genes were selected for testing. Minimal
inhibitory concentration was determined by broth dilution method. Gene transcript
levels on single and combined treatments were done in vitro and in vivo by qRT
PCR. Assessment of treatments was done in BALB/c mice according to a specific
protocol. As such, the qRT-PCR revealed a significant decrease of transcript
levels in all isolates upon using rifampicin or tigecycline, singly or in
combination with colistin. However, variable levels were obtained using colistin
singly or in combination with meropenem or fosfomycin. In vivo assessment showed
that all combinations used were effective against isolates harboring bla CTXM-15,
bla OXA-48, and bla NDM-1. Conversely, the most significant combination against
the isolate harboring bla KPC-2 gene was colistin with either carbapenem,
fosfomycin, or kanamycin. As a conclusion, combination therapy selected based on
the type of carbapenemase produced, appeared to be non-toxic and might be
effective in BALB/c mice. Therefore, the use of a rationally optimized
combination therapy might lead to better results than monotherapy, however,
clinical trials are needed for human consumption.
PMID- 26441927
TI - Assessment of the rabbit as a wildlife reservoir of bovine viral diarrhea virus:
serological analysis and generation of trans-placentally infected offspring.
AB - Eradication of bovine viral diarrhea virus (BVDV) is ongoing in many European
countries and is based on removal of persistently infected (PI) cattle. In this
context, low-level risks, including alternative reservoirs of infection, may
become more important as the number of BVDV-free herds increases. Alternative
reservoirs include livestock, such as sheep and goats, as well as wildlife,
including deer and rabbits. Due to the extensive nature of the beef industry in
Scotland, where an eradication program started in 2010, contact between cattle
and alternative reservoir hosts is common. Seroprevalence to BVDV in rabbit
populations can be high. In addition, rabbits can be infected with BVDV by
natural routes, indicating that they could be a wildlife reservoir of infection.
We analyzed the potential risk to livestock from rabbit populations in the UK by
two approaches. First, ~260 serum samples from free-ranging wild rabbits in
Scotland and northern England were tested for BVDV-specific antibodies by ELISA.
Only three samples exhibited low level BVDV-specific reactivity, suggesting that
BVDV infection of rabbits was not frequent. Second, rabbits were challenged with
BVDV at day 7 or 12 of pregnancy. This did not lead to any clinical signs in the
infected animals or obvious increases in abortion or stillbirth in the infected
dams. Samples from the dams, placental material and ~130 offspring were tested by
BVDV-specific RT-PCR and antibody ELISA. Positive PCR results in the placentas
and in the tissues and body fluids of rabbits up to 10 days old showed that trans
placental infection of rabbits with BVDV had occurred. Many of the offspring had
BVDV-specific antibodies. These data support the view that a wildlife reservoir
of BVDV in rabbit poses a small but non-zero risk of re-infection for BVDV-free
cattle herds. Rabbits are susceptible to infection with BVDV but only a small
proportion of free-living rabbits in the UK appear to have been infected.
PMID- 26441928
TI - Interaction of fibrinogen and muramidase-released protein promotes the
development of Streptococcus suis meningitis.
AB - Muramidase-released protein (MRP) is as an important virulence marker of
Streptococcus suis (S. suis) serotype 2. Our previous works have shown that MRP
can bind human fibrinogen (hFg); however, the function of this interaction in S.
suis meningitis is not known. In this study, we found that the deletion of mrp
significantly impairs the hFg-mediated adherence and traversal ability of S. suis
across human cerebral microvascular endothelial cells (hCMEC/D3). Measurement of
the permeability to Lucifer yellow in vitro and Evans blue extravasation in vivo
show that the MRP-hFg interaction significantly increases the permeability of the
blood-brain barrier (BBB). In the mouse meningitis model, wild type S. suis
caused higher bacterial loads in the brain and more severe histopathological
signs of meningitis than the mrp mutant at day 3 post-infection. Western blot
analysis and immunofluorescence observations reveal that the MRP-hFg interaction
can destroy the cell adherens junction protein p120-catenin of hCMEC/D3. These
results indicate that the MRP-hFg interaction is important in the development of
S. suis meningitis.
PMID- 26441929
TI - Recombinant protein production facility for fungal biomass-degrading enzymes
using the yeast Pichia pastoris.
AB - Filamentous fungi are the predominant source of lignocellulolytic enzymes used in
industry for the transformation of plant biomass into high-value molecules and
biofuels. The rapidity with which new fungal genomic and post-genomic data are
being produced is vastly outpacing functional studies. This underscores the
critical need for developing platforms dedicated to the recombinant expression of
enzymes lacking confident functional annotation, a prerequisite to their
functional and structural study. In the last decade, the yeast Pichia pastoris
has become increasingly popular as a host for the production of fungal biomass
degrading enzymes, and particularly carbohydrate-active enzymes (CAZymes). This
study aimed at setting-up a platform to easily and quickly screen the
extracellular expression of biomass-degrading enzymes in P. pastoris. We first
used three fungal glycoside hydrolases (GHs) that we previously expressed using
the protocol devised by Invitrogen to try different modifications of the original
protocol. Considering the gain in time and convenience provided by the new
protocol, we used it as basis to set-up the facility and produce a suite of
fungal CAZymes (GHs, carbohydrate esterases and auxiliary activity enzyme
families) out of which more than 70% were successfully expressed. The platform
tasks range from gene cloning to automated protein purifications and activity
tests, and is open to the CAZyme users' community.
PMID- 26441930
TI - Pichia pastoris-expressed dengue 3 envelope-based virus-like particles elicit
predominantly domain III-focused high titer neutralizing antibodies.
AB - Dengue poses a serious public health risk to nearly half the global population.
It causes ~400 million infections annually and is considered to be one of the
fastest spreading vector-borne diseases. Four distinct serotypes of dengue
viruses (DENV-1, -2, -3, and -4) cause dengue disease, which may be either mild
or extremely severe. Antibody-dependent enhancement (ADE), by pre-existing cross
reactive antibodies, is considered to be the major mechanism underlying severe
disease. This mandates that a preventive vaccine must confer simultaneous and
durable immunity to each of the four prevalent DENV serotypes. Recently, we used
Pichia pastoris, to express recombinant DENV-2 E ectodomain, and found that it
assembled into virus-like particles (VLPs), in the absence of prM, implicated in
the elicitation of ADE-mediating antibodies. These VLPs elicited predominantly
type-specific neutralizing antibodies that conferred significant protection
against lethal DENV-2 challenge, in a mouse model. The current work is an
extension of this approach to develop prM-lacking DENV-3 E VLPs. Our data reveal
that P. pastoris-produced DENV-3 E VLPs not only preserve the antigenic integrity
of the major neutralizing epitopes, but also elicit potent DENV-3 virus
neutralizing antibodies. Further, these neutralizing antibodies appear to be
exclusively directed toward domain III of the DENV-3 E VLPs. Significantly, they
also lack discernible ADE potential toward heterotypic DENVs. Taken together with
the high productivity of the P. pastoris expression system, this approach could
potentially pave the way toward developing a DENV E-based, inexpensive, safe, and
efficacious tetravalent sub-unit vaccine, for use in resource-poor dengue endemic
countries.
PMID- 26441931
TI - Effects of sub-lethal high-pressure homogenization treatment on the outermost
cellular structures and the volatile-molecule profiles of two strains of
probiotic lactobacilli.
AB - Applying sub-lethal levels of high-pressure homogenization (HPH) to lactic acid
bacteria has been proposed as a method of enhancing some of their functional
properties. Because the principal targets of HPH are the cell-surface structures,
the aim of this study was to examine the effect of sub-lethal HPH treatment on
the outermost cellular structures and the proteomic profiles of two known
probiotic bacterial strains. Moreover, the effect of HPH treatment on the
metabolism of probiotic cells within a dairy product during its refrigerated
storage was investigated using SPME-GC-MS. Transmission electron microscopy was
used to examine the microstructural changes in the outermost cellular structures
due to HPH treatment. These alterations may be involved in the changes in some of
the technological and functional properties of the strains that were observed
after pressure treatment. Moreover, the proteomic profiles of the probiotic
strains treated with HPH and incubated at 37 degrees C for various periods showed
different peptide patterns compared with those of the untreated cells. In
addition, there were differences in the peaks that were observed in the low-mass
spectral region (2000-3000 Da) of the spectral profiles of the control and
treated samples. Due to pressure treatment, the volatile-molecule profiles of
buttermilk inoculated with treated or control cells and stored at 4 degrees C for
30 days exhibited overall changes in the aroma profile and in the production of
molecules that improved its sensory profile, although the two different species
imparted specific fingerprints to the product. The results of this study will
contribute to understanding the changes that occur in the outermost cellular
structures and the metabolism of LAB in response to HPH treatment. The findings
of this investigation may contribute to elucidating the relationships between
these changes and the alterations of the technological and functional properties
of LAB induced by pressure treatment.
PMID- 26441932
TI - New process for production of fermented black table olives using selected
autochthonous microbial resources.
AB - Table olives represent one important fermented product in Europe and, in the
world, their demand is constantly increasing. At the present time, no systems are
available to control black table olives spontaneous fermentation by the Greek
method. During this study, a new protocol for the production of black table
olives belonging to two Italian (Cellina di Nardo and Leccino) and two Greek
(Kalamata and Conservolea) cultivars has been developed: for each table olive
cultivar, starter-driven fermentations were performed inoculating, firstly, one
selected autochthonous yeast starter and, subsequently, one selected
autochthonous LAB starter. All starters formulation were able to dominate
fermentation process. The olive fermentation was monitored using specific
chemical descriptors able to identify a first stage (30 days) mainly
characterized by aldehydes; a second period (60 days) mainly characterized by
higher alcohols, styrene and terpenes; a third fermentation stage represented by
acetate esters, esters and acids. A significant decrease of fermentation time
(from 8 to 12 months to a maximum of 3 months) and an significant improvement in
organoleptic characteristics of the final product were obtained. This study, for
the first time, describes the employment of selected autochthonous microbial
resources optimized to mimic the microbial evolution already recorded during
spontaneous fermentations.
PMID- 26441933
TI - Bacterial endophyte communities in the foliage of coast redwood and giant
sequoia.
AB - The endophytic bacterial microbiome, with an emerging role in plant nutrient
acquisition and stress tolerance, is much less studied in natural plant
populations than in agricultural crops. In a previous study, we found consistent
associations between trees in the pine family and acetic acid bacteria (AAB)
occurring at high relative abundance inside their needles. Our objective here was
to determine if that pattern may be general to conifers, or alternatively, is
more likely restricted to pines or conifers growing in nutrient limited and
exposed environments. We used 16S rRNA pyrosequencing to characterize the foliar
endophyte communities of two conifers in the Cupressaceae family: Two coast
redwood (CR; Sequoia sempervirens) populations and one giant sequoia (GS;
Sequoiadendron giganteum) population were sampled. Similar to the pines, the
endophyte communities of the giant trees were dominated by Proteobacteria,
Firmicutes, Acidobacteria, and Actinobacteria. However, although some major
operational taxonomic units (OTUs) occurred at a high relative abundance of 10
40% in multiple samples, no specific group of bacteria dominated the endophyte
community to the extent previously observed in high-elevation pines. Several of
the dominating bacterial groups in the CR and GS foliage (e.g., Bacillus,
Burkholderia, Actinomycetes) are known for disease- and pest suppression, raising
the possibility that the endophytic microbiome protects the giant trees against
biotic stress. Many of the most common and abundant OTUs in our dataset were most
similar to 16S rRNA sequences from bacteria found in lichens or arctic plants.
For example, an OTU belonging to the uncultured Rhizobiales LAR1 lineage, which
is commonly associated with lichens, was observed at high relative abundance in
many of the CR samples. The taxa shared between the giant trees, arctic plants,
and lichens may be part of a broadly defined endophyte microbiome common to
temperate, boreal, and tundra ecosystems.
PMID- 26441934
TI - Anthrax prophylaxis: recent advances and future directions.
AB - Anthrax is a serious, potentially fatal disease that can present in four distinct
clinical patterns depending on the route of infection (cutaneous,
gastrointestinal, pneumonic, or injectional); effective strategies for
prophylaxis and therapy are therefore required. This review addresses the complex
mechanisms of pathogenesis employed by the bacterium and describes how, as
understanding of these has developed over many years, so too have current
strategies for vaccination and therapy. It covers the clinical and veterinary use
of live attenuated strains of anthrax and the subsequent identification of
protein sub-units for incorporation into vaccines, as well as combinations of
protein sub-units with spore or other components. It also addresses the
application of these vaccines for conventional prophylactic use, as well as post
exposure use in conjunction with antibiotics. It describes the licensed acellular
vaccines AVA and AVP and discusses the prospects for a next generation of
recombinant sub-unit vaccines for anthrax, balancing the regulatory requirement
and current drive for highly defined vaccines, against the risk of losing the
"danger" signals required to induce protective immunity in the vaccinee. It
considers novel approaches to reduce time to immunity by means of combining, for
example, dendritic cell vaccination with conventional approaches and considers
current opportunities for the immunotherapy of anthrax.
PMID- 26441935
TI - Organogel-nanoemulsion containing nisin and D-limonene and its antimicrobial
activity.
AB - The aim of this study was to investigate a novel delivery system containing D
limonene and nisin by food organogel-nanoemulsion and study its effect on the
antimicrobial activity. Organogel-nanoemulsion containing with D-limonene and
nisin or without nisin was prepared by a homogenization method. Factors that may
affect the droplet size and stability of organogel-nanoemulsion such as pressure
and surfactant to oil ratio (SOR) were studied. The average droplet size
decreased with pressure, and the organogel-nanoemulsion could achieve good
stability at low SOR. Positive effects and outstanding antimicrobial activities
of organogel-nanoemulsion containing with D-limonene and nisin were confirmed by
minimal inhibitory concentrations comparison, growth curves of bacteria, scanning
electron microscopy and determination of cell constituents' release. Furthermore,
the organogel-nanoemulsion applied as food preservative in milk also shown
excellent antimicrobial performance. Overall, the research described in the
current article show that organogel-nanoemulsion containing with D-limonene and
nisin may be an effective antimicrobial system for the production and
preservation of food.
PMID- 26441936
TI - Control regions for chromosome replication are conserved with respect to sequence
and location among Escherichia coli strains.
AB - In Escherichia coli, chromosome replication is initiated from oriC by the DnaA
initiator protein associated with ATP. Three non-coding regions contribute to the
activity of DnaA. The datA locus is instrumental in conversion of DnaA(ATP) to
DnaA(ADP) (datA dependent DnaA(ATP) hydrolysis) whereas DnaA rejuvenation
sequences 1 and 2 (DARS1 and DARS2) reactivate DnaA(ADP) to DnaA(ATP). The
structural organization of oriC, datA, DARS1, and DARS2 were found conserved
among 59 fully sequenced E. coli genomes, with differences primarily in the non
functional spacer regions between key protein binding sites. The relative
distances from oriC to datA, DARS1, and DARS2, respectively, was also conserved
despite of large variations in genome size, suggesting that the gene dosage of
either region is important for bacterial growth. Yet all three regions could be
deleted alone or in combination without loss of viability. Competition
experiments during balanced growth in rich medium and during mouse colonization
indicated roles of datA, DARS1, and DARS2 for bacterial fitness although the
relative contribution of each region differed between growth conditions. We
suggest that this fitness advantage has contributed to conservation of both
sequence and chromosomal location for datA, DARS1, and DARS2.
PMID- 26441938
TI - Corrigendum: Leishmanicidal activities of Artemisia annua leaf essential oil
against Visceral Leishmaniasis.
AB - [This corrects the article on p. 626 in vol. 5, PMID: 25505453.].
PMID- 26441939
TI - Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the
antiretroviral therapy era.
AB - Human Cytomegalovirus (CMV) is a well-recognized pathogen in the context of HIV
infection, but since the roll out of ART, clinical and scientific interest in the
problem of HIV/CMV coinfection has diminished. However, CMV remains a significant
cofactor in HIV disease, with an influence on HIV acquisition, disease
progression, morbidity, and mortality. Disease manifestations may be a result of
direct interplay between the two viruses, or may arise as a secondary consequence
of immune dysregulation and systemic inflammation. The problem is most relevant
when the rates of coinfection are high, most notably in sub-Saharan Africa, and
in children at risk of acquiring both infections early in life. Understanding the
interplay between these viruses and developing strategies to diagnose, treat and
prevent CMV should be a priority.
PMID- 26441937
TI - Thermophilic and alkaliphilic Actinobacteria: biology and potential applications.
AB - Microbes belonging to the phylum Actinobacteria are prolific sources of
antibiotics, clinically useful bioactive compounds and industrially important
enzymes. The focus of the current review is on the diversity and potential
applications of thermophilic and alkaliphilic actinobacteria, which are highly
diverse in their taxonomy and morphology with a variety of adaptations for
surviving and thriving in hostile environments. The specific metabolic pathways
in these actinobacteria are activated for elaborating pharmaceutically,
agriculturally, and biotechnologically relevant biomolecules/bioactive compounds,
which find multifarious applications.
PMID- 26441940
TI - Targeted metagenomics unveils the molecular basis for adaptive evolution of
enzymes to their environment.
AB - Microorganisms have a wonderful ability to adapt rapidly to new or altered
environmental conditions. Enzymes are the basis of metabolism in all living
organisms and, therefore, enzyme adaptation plays a crucial role in the
adaptation of microorganisms. Comparisons of homology and parallel beneficial
mutations in an enzyme family provide valuable hints of how an enzyme adapted to
an ecological system; consequently, a series of enzyme collections is required to
investigate enzyme evolution. Targeted metagenomics is a promising tool for the
construction of enzyme pools and for studying the adaptive evolution of enzymes.
This perspective article presents a summary of targeted metagenomic approaches
useful for this purpose.
PMID- 26441941
TI - Mannitol metabolism during pathogenic fungal-host interactions under stressed
conditions.
AB - Numerous plants and fungi produce mannitol, which may serve as an osmolyte or
metabolic store; furthermore, mannitol also acts as a powerful quencher of
reactive oxygen species (ROS). Some phytopathogenic fungi use mannitol to stifle
ROS-mediated plant resistance. Mannitol is essential in pathogenesis to balance
cell reinforcements produced by both plants and animals. Mannitol likewise serves
as a source of reducing power, managing coenzymes, and controlling cytoplasmic pH
by going about as a sink or hotspot for protons. The metabolic pathways for
mannitol biosynthesis and catabolism have been characterized in filamentous fungi
by direct diminishment of fructose-6-phosphate into mannitol-1-phosphate
including a mannitol-1-phosphate phosphatase catalyst. In plants mannitol is
integrated from mannose-6-phosphate to mannitol-1-phosphate, which then
dephosphorylates to mannitol. The enzyme mannitol dehydrogenase plays a key role
in host-pathogen interactions and must be co-localized with pathogen-secreted
mannitol to resist the infection.
PMID- 26441942
TI - On Lactococcus lactis UL719 competitivity and nisin (Nisaplin((r))) capacity to
inhibit Clostridium difficile in a model of human colon.
AB - Clostridium difficile is the most frequently identified enteric pathogen in
patients with nosocomially acquired, antibiotic-associated diarrhea and
pseudomembranous colitis. Although metronidazole and vancomycin were effective,
an increasing number of treatment failures and recurrence of C. difficile
infection are being reported. Use of probiotics, particularly metabolically
active lactic acid bacteria, was recently proposed as an alternative for the
medical community. The aim of this study was to assess a probiotic candidate,
nisin Z-producer Lactococcus lactis UL719, competitivity and nisin
(Nisaplin((r))) capacity to inhibit C. difficile in a model of human colon.
Bacterial populations was enumerated by qPCR coupled to PMA treatment. L. lactis
UL719 was able to survive and proliferate under simulated human colon, did not
alter microbiota composition, but failed to inhibit C. difficile. While a single
dose of 19 MUmol/L (5* the MIC) was not sufficient to inhibit C. difficile, nisin
at 76 MUmol/L (20*the MIC) was effective at killing the pathogen. Nisin (at 76
MUmol/L) caused some temporary changes in the microbiota with Gram-positive
bacteria being the mostly affected. These results highlight the capacity of L.
lactis UL719 to survive under simulated human colon and the efficacy of nisin as
an alternative in the treatment of C. difficile infections.
PMID- 26441943
TI - Diversity of cultivable protease-producing bacteria in sediments of Jiaozhou Bay,
China.
AB - Although protease-producing bacteria are key players in the degradation of
organic nitrogen and essential for the nitrogen recycling in marine sediments,
diversity of both these bacteria and their extracellular proteases is still
largely unknown. This study investigated the diversity of the cultivable protease
producing bacteria and their extracellular proteases in the sediments of the
eutrophied Jiaozhou Bay, China through phylogenetic analysis and protease
inhibitor tests. The abundance of the cultivable protease-producing bacteria was
up to 10(4) cells/g in all six sediment samples. The cultivated protease
producing bacteria mostly belonged to the phyla Proteobacteria and Firmicutes
with the predominant genera being Photobacterium (39.4%), Bacillus (25.8%), and
Vibrio (19.7%). Protease inhibitor tests revealed that extracellular proteases
secreted by the bacteria were mainly serine proteases and/or metalloproteases
with relatively low proportions of cysteine proteases. This study represents the
first comprehensive analysis on the diversity of protease-producing bacteria and
their extracellular proteases in sediments of a eutrophic bay.
PMID- 26441944
TI - Temporal stability of bacterial symbionts in a temperate ascidian.
AB - In temperate seas, both bacterioplankton communities and invertebrate lifecycles
follow a seasonal pattern. To investigate whether the bacterial community
associated with the Mediterranean ascidian Didemnum fulgens exhibited similar
variations, we monitored its bacterial community structure monthly for over a
year using terminal restriction fragment length polymorphism and clone library
analyses based on a nearly full length fragment of the 16S rRNA gene. D. fulgens
harbored a bacterial consortium typical of ascidians, including numerous members
of the phylum Proteobacteria, and a few members of the phyla Cyanobacteria and
Acidobacteria. The overall bacterial community in D. fulgens had a distinct
signature from the surrounding seawater and was stable over time and across
seasonal fluctuations in temperature. Bacterial symbionts were also observed
around animal cells in the tunic of adult individuals and in the inner tunic of
D. fulgens larvae by transmission electron microscopy. Our results suggest that,
as seen for sponges and corals, some species of ascidians host stable and unique
bacterial communities that are at least partially inherited by their progeny by
vertical transmission.
PMID- 26441946
TI - Nucleation of Fe-rich phosphates and carbonates on microbial cells and
exopolymeric substances.
AB - Although phosphate and carbonate are important constituents in ancient and modern
environments, it is not yet clear their biogeochemical relationships and their
mechanisms of formation. Microbially mediated carbonate formation has been widely
studied whereas little is known about the formation of phosphate minerals. Here
we report that a new bacterial strain, Tessarococcus lapidicaptus, isolated from
the subsurface of Rio Tinto basin (Huelva, SW Spain), is capable of precipitating
Fe-rich phosphate and carbonate minerals. We observed morphological differences
between phosphate and carbonate, which may help us to recognize these minerals in
terrestrial and extraterrestrial environments. Finally, considering the scarcity
and the unequal distribution and preservation patterns of phosphate and
carbonates, respectively, in the geological record and the biomineralization
process that produces those minerals, we propose a hypothesis for the lack of Fe
phosphates in natural environments and ancient rocks.
PMID- 26441945
TI - Expression of the translocator protein (TSPO) from Pseudomonas fluorescens Pf0-1
requires the stress regulatory sigma factors AlgU and RpoH.
AB - The translocator protein (TSPO), previously designated as peripheral-type
benzodiazepine receptor, is an evolutionary conserved protein that is found in
many Eukarya, Archae, and Bacteria, in which it plays several important functions
including for example membrane biogenesis, signaling, and stress response. A tspo
homolog gene has been identified in several members of the Pseudomonas genus,
among which the soil bacterium P. fluorescens Pf0-1. In this bacterium, the tspo
gene is located in the vicinity of a putative hybrid histidine kinase-encoding
gene. Since tspo has been involved in water stress related response in plants, we
explored the effects of hyperosmolarity and temperature on P. fluorescens Pf0-1
tspo expression using a strategy based on lux-reporter fusions. We show that the
two genes Pfl01_2810 and tspo are co-transcribed forming a transcription unit.
The expression of this operon is growth phase-dependent and is increased in
response to high concentrations of NaCl, sucrose and to a D-cycloserine
treatment, which are conditions leading to activity of the major cell wall stress
responsive extracytoplasmic sigma factor AlgU. Interestingly, the promoter region
activity is strongly lowered in a P. aeruginosa algU mutant, suggesting that AlgU
may be involved at least partly in the molecular mechanism leading to Pfl01_2810
tspo expression. In silico analysis of this promoter region failed to detect an
AlgU consensus binding site; however, a putative binding site for the heat shock
response RpoH sigma factor was detected. Accordingly, the promoter activity of
the region containing this sequence is increased in response to high growth
temperature and slightly lowered in a P. aeruginosa rpoH mutant strain. Taken
together, our data suggest that P. fluorescens tspo gene may belong at least
partly to the cell wall stress response.
PMID- 26441947
TI - Exploring antibiotic resistance genes and metal resistance genes in plasmid
metagenomes from wastewater treatment plants.
AB - Plasmids operate as independent genetic elements in microorganism communities.
Through horizontal gene transfer (HGT), they can provide their host
microorganisms with important functions such as antibiotic resistance and heavy
metal resistance. In this study, six metagenomic libraries were constructed with
plasmid DNA extracted from influent, activated sludge (AS) and digested sludge
(DS) of two wastewater treatment plants (WWTPs). Compared with the metagenomes of
the total DNA extracted from the same sectors of the wastewater treatment plant,
the plasmid metagenomes had significantly higher annotation rates, indicating
that the functional genes on plasmids are commonly shared by those studied
microorganisms. Meanwhile, the plasmid metagenomes also encoded many more genes
related to defense mechanisms, including ARGs. Searching against an antibiotic
resistance genes (ARGs) database and a metal resistance genes (MRGs) database
revealed a broad-spectrum of antibiotic (323 out of a total 618 subtypes) and
MRGs (23 out of a total 23 types) on these plasmid metagenomes. The influent
plasmid metagenomes contained many more resistance genes (both ARGs and MRGs)
than the AS and the DS metagenomes. Sixteen novel plasmids with a complete
circular structure that carried these resistance genes were assembled from the
plasmid metagenomes. The results of this study demonstrated that the plasmids in
WWTPs could be important reservoirs for resistance genes, and may play a
significant role in the horizontal transfer of these genes.
PMID- 26441949
TI - Commentary: With a little help from my enteric microbial friends.
PMID- 26441950
TI - Glycan cross-feeding activities between bifidobacteria under in vitro conditions.
AB - Bifidobacteria colonize the gut of various mammals, including humans, where they
may metabolize complex, diet-, and host-derived carbohydrates. The glycan
associated metabolic features encoded by bifidobacteria are believed to be
strongly influenced by cross-feeding activities due to the co-existence of
strains with different glycan-degrading properties. In this study, we observed an
enhanced growth yield of Bifidobacterium bifidum PRL2010 when co-cultivated with
Bifidobacterium breve 12L, Bifidobacterium adolescentis 22L, or Bifidobacterium
thermophilum JCM1207. This enhanced growth phenomenon was confirmed by whole
genome transcriptome analyses, which revealed co-cultivation-associated
transcriptional induction of PRL2010 genes involved in carbohydrate metabolism,
such as those encoding for carbohydrate transporters and associated energy
production, and genes required for translation, ribosomal structure, and
biogenesis, thus supporting the idea that co-cultivation of certain
bifidobacterial strains with B. bifidum PRL2010 causes enhanced metabolic
activity, and consequently increased lactate and/or acetate production. Overall,
these data suggest that PRL2010 cells benefit from the presence of other
bifidobacterial strains.
PMID- 26441948
TI - Next-generation sequencing (NGS) for assessment of microbial water quality:
current progress, challenges, and future opportunities.
AB - Water quality is an emergent property of a complex system comprised of
interacting microbial populations and introduced microbial and chemical
contaminants. Studies leveraging next-generation sequencing (NGS) technologies
are providing new insights into the ecology of microbially mediated processes
that influence fresh water quality such as algal blooms, contaminant
biodegradation, and pathogen dissemination. In addition, sequencing methods
targeting small subunit (SSU) rRNA hypervariable regions have allowed
identification of signature microbial species that serve as bioindicators for
sewage contamination in these environments. Beyond amplicon sequencing,
metagenomic and metatranscriptomic analyses of microbial communities in fresh
water environments reveal the genetic capabilities and interplay of waterborne
microorganisms, shedding light on the mechanisms for production and
biodegradation of toxins and other contaminants. This review discusses the
challenges and benefits of applying NGS-based methods to water quality research
and assessment. We will consider the suitability and biases inherent in the
application of NGS as a screening tool for assessment of biological risks and
discuss the potential and limitations for direct quantitative interpretation of
NGS data. Secondly, we will examine case studies from recent literature where NGS
based methods have been applied to topics in water quality assessment, including
development of bioindicators for sewage pollution and microbial source tracking,
characterizing the distribution of toxin and antibiotic resistance genes in water
samples, and investigating mechanisms of biodegradation of harmful pollutants
that threaten water quality. Finally, we provide a short review of emerging NGS
platforms and their potential applications to the next generation of water
quality assessment tools.
PMID- 26441951
TI - Phenotype MicroArrays as a complementary tool to next generation sequencing for
characterization of tree endophytes.
AB - There is an increasing need to calibrate microbial community profiles obtained
through next generation sequencing (NGS) with relevant taxonomic identities of
the microbes, and to further associate these identities with phenotypic
attributes. Phenotype MicroArray (PM) techniques provide a semi-high throughput
assay for characterization and monitoring the microbial cellular phenotypes.
Here, we present detailed descriptions of two different PM protocols used in our
recent studies on fungal endophytes of forest trees, and highlight the benefits
and limitations of this technique. We found that the PM approach enables
effective screening of substrate utilization by endophytes. However, the
technical limitations are multifaceted and the interpretation of the PM data
challenging. For the best result, we recommend that the growth conditions for the
fungi are carefully standardized. In addition, rigorous replication and control
strategies should be employed whether using pre-configured, commercial microwell
plates or in-house designed PM plates for targeted substrate analyses. With these
precautions, the PM technique is a valuable tool to characterize the metabolic
capabilities of individual endophyte isolates, or successional endophyte
communities identified by NGS, allowing a functional interpretation of the
taxonomic data. Thus, PM approaches can provide valuable complementary
information for NGS studies of fungal endophytes in forest trees.
PMID- 26441952
TI - Assessing the antimicrobial activities of Ocins.
AB - The generation of a zone of inhibition on a solid substrate indicates the
bioactivity of antimicrobial peptides such as bacteriocin and enterocin. The
indicator strain plays a significant role in bacteriocin assays. Other
characteristics of bacteriocins, such as their dispersal ability and the
different zymogram components, also affect bacteriocin assays. However, universal
well diffusion assays for antimicrobials, irrespective of their ability to
diffuse (bacteriocin and enterocin), do not exist. The ability of different
zymography components to generate non-specific activities have rarely been
explored in the literature. The purpose of the present work was to evaluate the
impact of major factors (diffusion and rate of diffusion) in a solid substrate
bioassay, and to document the adverse effects of sodium dodecyl sulfate in
zymograms used to estimate the approximate molecular weight of bacteriocins.
PMID- 26441953
TI - Epicatechin gallate, a naturally occurring polyphenol, alters the course of
infection with beta-lactam-resistant Staphylococcus aureus in the zebrafish
embryo.
AB - (-)-epicatechin gallate (ECg) substantially modifies the properties of
Staphylococcus aureus and reversibly abrogates beta-lactam resistance in
methicillin/oxacillin resistant (MRSA) isolates. We have determined the capacity
of ECg to alter the course of infection in zebrafish embryos challenged with
epidemic clinical isolate EMRSA-16. At 30 h post fertilization (hpf), embryos
were infected by injection of 1-5 * 10(3) colony forming units (CFU) of EMRSA-16
into the circulation valley or yolk sac. Infection by yolk sac injection was
lethal with a challenge dose above 3 * 10(3) CFU, with no survivors at 70 hpf. In
contrast, survival at 70 hpf after injection into the circulation was 83 and 44%
following challenge with 3 * 10(3) and 1-5 * 10(3) CFU, respectively. No
significant increases in survival were noted when infected embryos were
maintained in medium containing 12.5-100 MUg/mL ECg with or without 4 or 16
MUg/mL oxacillin. However, when EMRSA-16 was grown in medium containing 12.5
MUg/mL ECg and the bacteria used to infect embryos by either the circulation
valley or yolk sac, there were significant increases in embryo survival in both
the presence and absence of oxacillin. ECg-modified and unmodified, GFP
transformed EMRSA-16 bacteria were visualized within phagocytic cells in the
circulation and yolk sac; pre-treatment with ECg also significantly increased
induction of the respiratory burst and suppressed increases in IL-1beta
expression typical of infection with untreated EMRSA-16. We conclude that
exposure to ECg prior to infection reduces the lethality of EMRSA-16, renders
cells more susceptible to elimination by immune processes and compromises their
capacity to establish an inflammatory response in comparison to non-exposed
bacteria.
PMID- 26441954
TI - Epigenetic Codes Programing Class Switch Recombination.
AB - Class switch recombination imparts B cells with a fitness-associated adaptive
advantage during a humoral immune response by using a precision-tailored DNA
excision and ligation process to swap the default constant region gene of the
antibody with a new one that has unique effector functions. This secondary
diversification of the antibody repertoire is a hallmark of the adaptability of B
cells when confronted with environmental and pathogenic challenges. Given that
the nucleotide sequence of genes during class switching remains unchanged
(genetic constraints), it is logical and necessary therefore, to integrate the
adaptability of B cells to an epigenetic state, which is dynamic and can be
heritably modulated before, after, or even during an antibody-dependent immune
response. Epigenetic regulation encompasses heritable changes that affect
function (phenotype) without altering the sequence information embedded in a
gene, and include histone, DNA and RNA modifications. Here, we review current
literature on how B cells use an epigenetic code language as a means to ensure
antibody plasticity in light of pathogenic insults.
PMID- 26441955
TI - MF59- and Al(OH)3-Adjuvanted Staphylococcus aureus (4C-Staph) Vaccines Induce
Sustained Protective Humoral and Cellular Immune Responses, with a Critical Role
for Effector CD4 T Cells at Low Antibody Titers.
AB - Staphylococcus aureus (S. aureus) is an important opportunistic pathogen that may
cause invasive life-threatening infections, like sepsis and pneumonia. Due to the
increasing antibiotic resistance, the development of an effective vaccine against
S. aureus is needed. Although a correlate of protection against staphylococcal
diseases is not yet established, several findings suggest that both antibodies
and CD4 T cells might contribute to optimal immunity. In this study, we show that
adjuvanting a multivalent vaccine (4C-Staph) with MF59, an oil-in-water emulsion
licensed in human vaccines, further potentiated antigen-specific IgG titers and
CD4 T-cell responses compared to alum and conferred protection in the peritonitis
model of S. aureus infection. Moreover, we showed that MF59- and alum-adjuvanted
4C-Staph vaccines induced persistent antigen-specific humoral and T-cell
responses, and protected mice from infection up to 4 months after immunization.
Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune
compartment is involved in vaccine-induced protection. Using CD4 T cell-depleted
mice or B cell-deficient mice, we demonstrated that both T and B-cell responses
contributed to 4C-Staph vaccine-mediated protective immunity. However, the role
of CD4 T cells seemed more evident in the presence of low-antibody responses.
This study provides preclinical data further supporting the use of the adjuvanted
4C-Staph vaccines against S. aureus diseases, and provides critical insights on
the correlates of protective immunity necessary to combat this pathogen.
PMID- 26441959
TI - Whole Genome Expression Microarray Analysis of Highly Versus Poorly Tumorigenic
Murine Melanoma Cell Lines Provides Insights into Factors That Regulate Tumor
Growth, Metastasis, and Immunogenicity.
PMID- 26441956
TI - A Tale from TGF-beta Superfamily for Thymus Ontogeny and Function.
AB - Multiple signaling pathways control every aspect of cell behavior, organ
formation, and tissue homeostasis throughout the lifespan of any individual. This
review takes an ontogenetic view focused on the large superfamily of TGF
beta/bone morphogenetic protein ligands to address thymus morphogenesis and
function in T cell differentiation. Recent findings on a role of GDF11 for
reversing aging-related phenotypes are also discussed.
PMID- 26441958
TI - Subversion of Cell-Autonomous Immunity and Cell Migration by Legionella
pneumophila Effectors.
AB - Bacteria trigger host defense and inflammatory processes, such as cytokine
production, pyroptosis, and the chemotactic migration of immune cells toward the
source of infection. However, a number of pathogens interfere with these immune
functions by producing specific so-called "effector" proteins, which are
delivered to host cells via dedicated secretion systems. Air-borne Legionella
pneumophila bacteria trigger an acute and potential fatal inflammation in the
lung termed Legionnaires' disease. The opportunistic pathogen L. pneumophila is a
natural parasite of free-living amoebae, but also replicates in alveolar
macrophages and accidentally infects humans. The bacteria employ the
intracellular multiplication/defective for organelle trafficking (Icm/Dot) type
IV secretion system and as many as 300 different effector proteins to govern host
cell interactions and establish in phagocytes an intracellular replication niche,
the Legionella-containing vacuole. Some Icm/Dot-translocated effector proteins
target cell-autonomous immunity or cell migration, i.e., they interfere with (i)
endocytic, secretory, or retrograde vesicle trafficking pathways, (ii) organelle
or cell motility, (iii) the inflammasome and programed cell death, or (iv) the
transcription factor NF-kappaB. Here, we review recent mechanistic insights into
the subversion of cellular immune functions by L. pneumophila.
PMID- 26441957
TI - Modes of Antigen Presentation by Lymph Node Stromal Cells and Their Immunological
Implications.
AB - Antigen presentation is no longer the exclusive domain of cells of hematopoietic
origin. Recent works have demonstrated that lymph node stromal cell (LNSC)
populations, such as fibroblastic reticular cells, lymphatic and blood
endothelial cells, not only provide a scaffold for lymphocyte interactions but
also exhibit active immunomodulatory roles that are critical to mounting and
resolving effective immune responses. Importantly, LNSCs possess the ability to
present antigens and establish antigen-specific interactions with T cells. One
example is the expression of peripheral tissue antigens, which are presented on
major histocompatibility complex (MHC)-I molecules with tolerogenic consequences
on T cells. Additionally, exogenous antigens, including self and tumor antigens,
can be processed and presented on MHC-I complexes, which result in dysfunctional
activation of antigen-specific CD8(+) T cells. While MHC-I is widely expressed on
cells of both hematopoietic and non-hematopoietic origins, antigen presentation
via MHC-II is more precisely regulated. Nevertheless, LNSCs are capable of
endogenously expressing, or alternatively, acquiring MHC-II molecules. Transfer
of antigen between LNSC and dendritic cells in both directions has been recently
suggested to promote tolerogenic roles of LNSCs on the CD4(+) T cell compartment.
Thus, antigen presentation by LNSCs is thought to be a mechanism that promotes
the maintenance of peripheral tolerance as well as generates a pool of diverse
antigen-experienced T cells for protective immunity. This review aims to
integrate the current and emerging literature to highlight the importance of
LNSCs in immune responses, and emphasize their role in antigen trafficking,
retention, and presentation.
PMID- 26441960
TI - gammadelta T Cells and NK Cells - Distinct Pathogenic Roles as Innate-Like Immune
Cells in CNS Autoimmunity.
PMID- 26441963
TI - Computational Models for Transplant Biomarker Discovery.
AB - Translational medicine offers a rich promise for improved diagnostics and drug
discovery for biomedical research in the field of transplantation, where
continued unmet diagnostic and therapeutic needs persist. Current advent of
genomics and proteomics profiling called "omics" provides new resources to
develop novel biomarkers for clinical routine. Establishing such a marker system
heavily depends on appropriate applications of computational algorithms and
software, which are basically based on mathematical theories and models.
Understanding these theories would help to apply appropriate algorithms to ensure
biomarker systems successful. Here, we review the key advances in theories and
mathematical models relevant to transplant biomarker developments. Advantages and
limitations inherent inside these models are discussed. The principles of key
computational approaches for selecting efficiently the best subset of biomarkers
from high--dimensional omics data are highlighted. Prediction models are also
introduced, and the integration of multi-microarray data is also discussed.
Appreciating these key advances would help to accelerate the development of
clinically reliable biomarker systems.
PMID- 26441962
TI - Female Bias in Systemic Lupus Erythematosus is Associated with the Differential
Expression of X-Linked Toll-Like Receptor 8.
AB - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized
by the production of anti-nuclear antibodies. SLE is one of many autoimmune
disorders that have a strong gender bias, with 70-90% of SLE patients being
female. Several explanations have been postulated to account for the severity of
autoimmune diseases in females, including hormonal, microbiota, and gene dosage
differences. X-linked toll-like receptors (TLRs) have recently been implicated in
disease progression in females. Our previous studies using the 564Igi mouse model
of SLE on a Tlr7 and Tlr9 double knockout background showed that the presence of
Tlr8 on both X chromosomes was required for the production of IgG autoantibodies,
Ifn-I expression and granulopoiesis in females. Here, we show the results of our
investigation into the role of Tlr8 expression in SLE pathogenesis in 564Igi
females. Female mice have an increase in serum pathogenic anti-RNA IgG2a and
IgG2b autoantibodies. 564Igi mice have also been shown to have an increase in
neutrophils in vivo, which are major contributors to Ifn-alpha expression. Here,
we show that neutrophils from C57BL/6 mice express Ifn-alpha in response to 564
immune complexes and TLR8 activation. Bone marrow-derived macrophages from 564Igi
females have a significant increase in Tlr8 expression compared to male-derived
cells, and RNA fluorescence in situ hybridization data suggest that Tlr8 may
escape X-inactivation in female-derived macrophages. These results propose a
model by which females may be more susceptible to SLE pathogenesis due to
inefficient inactivation of Tlr8.
PMID- 26441961
TI - Development and Function of Protective and Pathologic Memory CD4 T Cells.
AB - Immunological memory is one of the defining features of the adaptive immune
system. As key orchestrators and mediators of immunity, CD4 T cells are central
to the vast majority of adaptive immune responses. Generated following an immune
response, memory CD4 T cells retain pertinent information about their activation
environment enabling them to make rapid effector responses upon reactivation.
These responses can either benefit the host by hastening the control of pathogens
or cause damaging immunopathology. Here, we will discuss the diversity of the
memory CD4 T cell pool, the signals that influence the transition of activated T
cells into that pool, and highlight how activation requirements differ between
naive and memory CD4 T cells. A greater understanding of these factors has the
potential to aid the design of more effective vaccines and to improve regulation
of pathologic CD4 T cells, such as in the context of autoimmunity and allergy.
PMID- 26441965
TI - Synergy between CD40 and MyD88 Does Not Influence Host Survival to Salmonella
Infection.
AB - Previous studies using purified toll-like receptor (TLR) ligands plus agonistic
anti-CD40 antibodies showed that TLRs and CD40 can act synergistically on
dendritic cells (DCs) to optimize T cell activation and Th1 differentiation.
However, a synergistic effect of TLRs and CD40 during bacterial infection is not
known. Here, we show that mice lacking the TLR adaptor MyD88 alone, or lacking
both MyD88 and CD40 [double knockout (DKO) mice], are compromised in survival to
Salmonella infection but have intact recruitment of neutrophils and inflammatory
monocytes as well as unaltered abundance of DC subsets and DC activation in
infected tissues. In contrast to infected wildtype and CD40(-/-) mice, both
MyD88(-/-) mice and DKO mice lack detectable serum IFN-gamma and have elevated IL
10. A synergistic effect of TLRs and CD40 was revealed in co-culture experiments
where OT-II T cell proliferation was compromised when DKO DCs were pulsed with
OVA protein and OVA323-339 peptide, but not with heat-killed Salmonella
expressing OVA (HKSOVA), relative to MyD88(-/-) DCs. By contrast, MyD88(-/-) or
DKO DCs pulsed with any of the antigens had a similar ability to induce IFN-gamma
that was lower than WT or CD40(-/-) DCs. DKO DCs pulsed with HKSOVA, but not with
OVA or OVA323-339, had increased IL-10 relative to MyD88(-/-) DCs. Finally,
HKSOVA-pulsed MyD88(-/-) and DKO DCs had similar and low induction of NFkappaB
dependent and -independent genes upon co-culture with OT-II cells. Overall, our
data revealed that synergistic effects of CD40 and MyD88 do not influence host
survival to Salmonella infection or serum levels of IFN-gamma or IL-10. However,
synergistic effects of MyD88 and CD40 may be apparent on some (IL-10 production)
but not all (OT-II proliferation and IFN-gamma production) DC functions and
depend on the complexity of the antigen. Indeed, synergistic effects observed
using purified ligands and well-defined antigens may not necessarily apply when
complex antigens, such as live bacteria, challenge the immune system.
PMID- 26441964
TI - Macroautophagy in Endogenous Processing of Self- and Pathogen-Derived Antigens
for MHC Class II Presentation.
AB - Although autophagy is a process that has been studied for several years its link
with antigen presentation and T cell immunity has only recently emerged.
Autophagy, which means "self-eating," is important to maintain cell homeostasis
and refers to a collection of mechanisms that delivers intracellular material for
degradation into lysosomes. Among them, macroautophagy pathway has many
implications in different biological processes, including innate and adaptive
immunity. In particular, macroautophagy can provide a substantial source of
intracellular antigens for loading onto MHC class II molecules using the
alternative MHC class II pathway. Through autophagosomes, endogenous self
antigens as well as antigens derived from intracellular pathogens can be
delivered to MHC class II compartment and presented to CD4(+) T cells. The
pathway will, therefore, impact both peripheral T cell tolerance and the pathogen
specific immune response. This review will describe the contribution of autophagy
to intracellular presentation of endogenous self- or pathogen-derived antigens
via MHC class II and its consequences on CD4(+) T cell responses.
PMID- 26441966
TI - Positive and Negative Regulatory Mechanisms for Fine-Tuning Cellularity and
Functions of Medullary Thymic Epithelial Cells.
AB - Self-tolerant T cells and regulatory T cells develop in the thymus. A wide
variety of cell-cell interactions in the thymus is required for the
differentiation, proliferation, and repertoire selection of T cells. Various
secreted and cell surface molecules expressed in thymic epithelial cells (TECs)
mediate these processes. Moreover, cytokines expressed by cells of hematopoietic
origin regulate the cellularity of TECs. Tumor necrosis factor (TNF) family RANK
ligand, lymphotoxin, and CD40 ligand, expressed in T cells and innate lymphoid
cells (ILCs), promote the differentiation and proliferation of medullary TECs
(mTECs) that play critical roles in the induction of immune tolerance. A recent
study suggests that interleukin-22 (IL-22) produced by ILCs promotes regeneration
of TECs after irradiation. Intriguingly, tumor growth factor-beta and
osteoprotegerin limit cellularity of mTECs, thereby attenuating regulatory T cell
generation. We will review recent insights into the molecular basis for cell-cell
interactions regulating differentiation and proliferation of mTECs and also
discuss about a perspective on use of mathematical models for understanding this
complicated system.
PMID- 26441967
TI - Transcriptional Enhancers in the Regulation of T Cell Differentiation.
AB - The changes in phenotype and function that characterize the differentiation of
naive T cells to effector and memory states are underscored by large-scale,
coordinated, and stable changes in gene expression. In turn, these changes are
choreographed by the interplay between transcription factors and epigenetic
regulators that act to restructure the genome, ultimately ensuring lineage
appropriate gene expression. Here, we focus on the mechanisms that control T cell
differentiation, with a particular focus on the role of regulatory elements
encoded within the genome, known as transcriptional enhancers (TEs). We discuss
the central role of TEs in regulating T cell differentiation, both in health and
disease.
PMID- 26441968
TI - Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood
Derived Myeloid Cells in Central Nervous System Inflammation.
AB - Inflammation is a series of processes designed for eventual clearance of
pathogens and repair of damaged tissue. In the context of autoimmune recognition,
inflammatory processes are usually considered to be pathological. This is also
true for inflammatory responses in the central nervous system (CNS). However, as
in other tissues, neuroinflammation can have beneficial as well as pathological
outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and
its animal model experimental autoimmune encephalomyelitis (EAE) may derive from
heterogeneity of the myeloid cells with which these T cells interact within the
CNS. Myeloid cells, including resident microglia and infiltrating bone marrow
derived cells, such as dendritic cells (DC) and monocytes/macrophages [bone
marrow-derived macrophages (BMDM)], are highly heterogeneous populations that may
be involved in neurotoxicity and also immunoregulation and regenerative
processes. Better understanding and characterization of myeloid cell
heterogeneity is essential for future development of treatments controlling
inflammation and inducing neuroprotection and neuroregeneration in diseased CNS.
Here, we describe and compare three populations of myeloid cells: CD11c(+)
microglia, CD11c(-) microglia, and CD11c(+) blood-derived cells in terms of their
pathological versus protective functions in the CNS of mice with EAE. Our data
show that CNS-resident microglia include functionally distinct subsets that can
be distinguished by their expression of CD11c. These subsets differ in their
expression of Arg-1, YM1, iNOS, IL-10, and IGF-1. Moreover, in contrast to
BMDM/DC, both subsets of microglia express protective interferon-beta (IFNbeta),
high levels of colony-stimulating factor-1 receptor, and do not express the Th1
associated transcription factor T-bet. Taken together, our data suggest that
CD11c(+) microglia, CD11c(-) microglia, and infiltrating BMDM/DC represent
separate and distinct populations and illustrate the heterogeneity of the CNS
inflammatory environment.
PMID- 26441969
TI - Endogenous Antigen Presentation of MHC Class II Epitopes through Non-Autophagic
Pathways.
AB - Antigenic peptides presented by major histocompatibility complex (MHC) class II
molecules are generally derived from exogenous proteins acquired by antigen
presenting cells. However, in some circumstances, MHC class II molecules can
present intracellular proteins expressed within the antigen-presenting cells.
There are several described pathways by which endogenous antigens are degraded
and gain access to MHC class II molecules. These include autophagy and other non
autophagic pathways; the latter category includes the MHC class I-like pathways,
heat shock protein 90-mediated pathways, and internalization from the plasma
membrane. This review will summarize and discuss the non-autophagic pathways.
PMID- 26441970
TI - Animal Models to Study Links between Cardiovascular Disease and Renal Failure and
Their Relevance to Human Pathology.
AB - The close association between cardiovascular pathology and renal dysfunction is
well documented and significant. Patients with conventional risk factors for
cardiovascular disease like diabetes and hypertension also suffer renal
dysfunction. This is unsurprising if the kidney is simply regarded as a "modified
blood vessel" and thus, traditional risk factors will affect both systems.
Consistent with this, it is relatively easy to comprehend how patients with
either sudden or gradual cardiac and or vascular compromise have changes in both
renal hemodynamic and regulatory systems. However, patients with pure or primary
renal dysfunction also have metabolic changes (e.g., oxidant stress,
inflammation, nitric oxide, or endocrine changes) that affect the cardiovascular
system. Thus, cardiovascular and renal systems are intimately, bidirectionally
and inextricably linked. Whilst we understand several of these links, some of the
mechanisms for these connections remain incompletely explained. Animal models of
cardiovascular and renal disease allow us to explore such mechanisms, and more
importantly, potential therapeutic strategies. In this article, we review various
experimental models used, and examine critically how representative they are of
the human condition.
PMID- 26441971
TI - Mucosal-Associated Invariant T Cells in the Human Gastric Mucosa and Blood: Role
in Helicobacter pylori Infection.
AB - Mucosal-associated invariant T (MAIT) cells represent a class of antimicrobial
innate-like T cells that have been characterized in human blood, liver, lungs,
and intestine. Here, we investigated, for the first time, the presence of MAIT
cells in the stomach of children, adults, and the elderly undergoing routine
endoscopy and assessed their reactivity to Helicobacter pylori (H. pylori - Hp),
a major gastric pathogen. We observed that MAIT cells are present in the lamina
propria compartment of the stomach and display a similar memory phenotype to
blood MAIT cells. We then demonstrated that gastric and blood MAIT cells are able
to recognize H. pylori. We found that CD8(+) and CD4(-)CD8(-) (double negative)
MAIT cell subsets respond to H. pylori-infected macrophages stimulation in a MR-1
restrictive manner by producing cytokines (IFN-gamma, TNF-alpha, IL-17A) and
exhibiting cytotoxic activity. Interestingly, we observed that blood MAIT cell
frequency in Hp(+ve) individuals was significantly lower than in Hp(-ve)
individuals. However, gastric MAIT cell frequency was not significantly different
between Hp(+ve) and Hp(-ve) individuals, demonstrating a dichotomy between blood
and gastric tissues. Further, we observed that the majority of gastric MAIT cells
(>80%) expressed tissue-resident markers (CD69(+) CD103(+)), which were only
marginally present on PBMC MAIT cells (<3%), suggesting that gastric MAIT cells
are readily available to respond quickly to pathogens. These results contribute
important new information to the understanding of MAIT cells function on
peripheral and mucosal tissues and its possible implications in the host response
to H. pylori.
PMID- 26441972
TI - Nutritional Modulation of Gene Expression: Might This be of Benefit to
Individuals with Crohn's Disease?
AB - The incidence of inflammatory bowel diseases (IBD), including Crohn's disease
(CD), is increasing worldwide, especially in young children and adolescents.
Although hospitalized patients are usually provided with enteral or parenteral
support, continuing care typically requires a trial-and-error approach to
suppressing symptoms and maintaining disease remission. Current nutritional
advice does not differ from general population guidelines. International
collaborative studies have revealed 163 distinct genetic loci affecting
susceptibility to IBD, in some of which host-microbe interactions can be seen to
play an important role. The nature of these loci enables a rationale for
predicting nutritional requirements that may not be evident through standard
therapeutic approaches. Certain recognized nutrients, such as vitamin D and long
chain omega-3 polyunsaturated fatty acids, may be required at higher than
anticipated levels. Various phytochemicals, not usually considered in the same
class as classic nutrients, could play an important role. Prebiotics and
probiotics may also be beneficial. Genomic approaches enable proof of principle
of nutrient optimization rather than waiting for disease symptoms to appear
and/or progress. We suggest a paradigm shift in diagnostic tools and nutritional
therapy for CD, involving a systems biology approach for implementation.
PMID- 26441973
TI - Lower Affinity T Cells are Critical Components and Active Participants of the
Immune Response.
AB - Kinetic and biophysical parameters of T cell receptor (TCR) and peptide:MHC
(pMHC) interaction define intrinsic factors required for T cell activation and
differentiation. Although receptor ligand kinetics are somewhat cumbersome to
assess experimentally, TCR:pMHC affinity has been shown to predict peripheral T
cell functionality and potential for forming memory. Multimeric forms of pMHC
monomers have often been used to provide an indirect readout of higher affinity T
cells due to their availability and ease of use while allowing simultaneous
definition of other functional and phenotypic characteristics. However,
multimeric pMHC reagents have introduced a bias that underestimates the lower
affinity components contained in the highly diverse TCR repertoires of all
polyclonal T cell responses. Advances in the identification of lower affinity
cells have led to the examination of these cells and their contribution to the
immune response. In this review, we discuss the identification of high- vs. low
affinity T cells as well as their attributed signaling and functional
differences. Lastly, mechanisms are discussed that maintain a diverse range of
low- and high-affinity T cells.
PMID- 26441974
TI - Induction of Regulatory T Cells by Intravenous Immunoglobulin: A Bridge between
Adaptive and Innate Immunity.
AB - Intravenous immunoglobulin (IVIg) is a polyclonal immunoglobulin G preparation
with potent immunomodulatory properties. The mode of action of IVIg has been
investigated in multiple disease states, with various mechanisms described to
account for its benefits. Recent data indicate that IVIg increases both the
number and the suppressive capacity of regulatory T cells, a subpopulation of T
cells that are essential for immune homeostasis. IVIg alters dendritic cell
function, cytokine and chemokine networks, and T lymphocytes, leading to
development of regulatory T cells. The ability of IVIg to influence Treg
induction has been shown both in animal models and in human diseases. In this
review, we discuss data on the potential mechanisms contributing to the
interaction between IVIg and the regulatory T-cell compartment.
PMID- 26441975
TI - Meningeal Infiltration of the Spinal Cord by Non-Classically Activated B Cells is
Associated with Chronic Disease Course in a Spontaneous B Cell-Dependent Model of
CNS Autoimmune Disease.
AB - We characterized B cell infiltration of the spinal cord in a B cell-dependent
spontaneous model of central nervous system (CNS) autoimmunity that develops in a
proportion of mice with mutant T and B cell receptors specific for myelin
oligodendrocyte glycoprotein. We found that, while males are more likely to
develop disease, females are more likely to have a chronic rather than monophasic
disease course. B cell infiltration of the spinal cord was investigated by
histology and FACs. CD4(+) T cell infiltration was pervasive throughout the white
and in some cases gray matter. B cells were almost exclusively restricted to the
meninges, often in clusters reminiscent of those described in human multiple
sclerosis. These clusters were typically found adjacent to white matter lesions
and their presence was associated with a chronic disease course. Extensive
investigation of these clusters by histology did not identify features of
lymphoid follicles, including organization of T and B cells into separate zones,
CD35(+) follicular dendritic cells, or germinal centers. The majority of cluster
B cells were IgD(+) with little evidence of class switch. Consistent with this, B
cells isolated from the spinal cord were of the naive/memory CD38(hi) CD95(lo)
phenotype. Nevertheless, they were CD62L(lo) and CD80(hi) compared to lymph node
B cells suggesting that they were at least partly activated and primed to present
antigen. Therefore, if meningeal B cells contribute to CNS pathology in
autoimmunity, follicular differentiation is not necessary for the pathogenic
mechanism.
PMID- 26441976
TI - How Neutrophils Shape Adaptive Immune Responses.
AB - Neutrophils are classically considered as cells pivotal for the first line of
defense against invading pathogens. In recent years, evidence has accumulated
that they are also important in the orchestration of adaptive immunity.
Neutrophils rapidly migrate in high numbers to sites of inflammation (e.g.,
infection, tissue damage, and cancer) and are subsequently able to migrate to
draining lymph nodes (LNs). Both at the site of inflammation as well as in the
LNs, neutrophils can engage with lymphocytes and antigen-presenting cells. This
crosstalk occurs either directly via cell-cell contact or via mediators, such as
proteases, cytokines, and radical oxygen species. In this review, we will discuss
the current knowledge regarding locations and mechanisms of interaction between
neutrophils and lymphocytes in the context of homeostasis and various
pathological conditions. In addition, we will highlight the complexity of the
microenvironment that is involved in the generation of suppressive or stimulatory
neutrophil phenotypes.
PMID- 26441977
TI - The Fyn-ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells.
AB - Lymphocyte signaling cascades responsible for anti-tumor cytotoxicity and
inflammatory cytokine production must be tightly regulated in order to control an
immune response. Disruption of these cascades can cause immune suppression as
seen in a tumor microenvironment, and loss of signaling integrity can lead to
autoimmunity and other forms of host-tissue damage. Therefore, understanding the
distinct signaling events that exclusively control specific effector functions of
"killer" lymphocytes (T and NK cells) is critical for understanding disease
progression and formulating successful immunotherapy. Elucidation of divergent
signaling pathways involved in receptor-mediated activation has provided insights
into the independent regulation of cytotoxicity and cytokine production in
lymphocytes. Specifically, the Fyn signaling axis represents a branch point for
killer cell effector functions and provides a model for how cytotoxicity and
cytokine production are differentially regulated. While the Fyn-PI(3)K pathway
controls multiple functions, including cytotoxicity, cell development, and
cytokine production, the Fyn-ADAP pathway preferentially regulates cytokine
production in NK and T cells. In this review, we discuss how the structure of Fyn
controls its function in lymphocytes and the role this plays in mediating two
facets of lymphocyte effector function, cytotoxicity and production of
inflammatory cytokines. This offers a model for using mechanistic and structural
approaches to understand clinically relevant lymphocyte signaling.
PMID- 26441978
TI - Role of Memory T Cells and Perspectives for Intervention in Organ
Transplantation.
AB - Memory T cells are necessary for protective immunity against invading pathogens,
especially under conditions of immunosuppression. However, their presence also
threatens transplant survival, making transplantation a great challenge.
Significant progress has been achieved in recent years in advancing our
understanding of the role that memory T cells play in transplantation. This
review focuses on the latest advances in our understanding of the involvement of
memory T cells in graft rejection and transplant tolerance and discusses
potential strategies for targeting memory T cells in order to minimize allograft
rejection and optimize clinical outcomes.
PMID- 26441979
TI - Controlling HIV-1: Non-Coding RNA Gene Therapy Approaches to a Functional Cure.
AB - The current treatment strategy for HIV-1 involves prolonged and intensive
combined antiretroviral therapy (cART), which successfully suppresses plasma
viremia. It has transformed HIV-1 infection into a chronic disease. However,
despite the success of cART, a latent form of HIV-1 infection persists as
integrated provirus in resting memory CD4(+) T cells. Virus can reactivate from
this reservoir upon cessation of treatment, and hence HIV requires lifelong
therapy. The reservoir represents a major barrier to eradication. Understanding
molecular mechanisms regulating HIV-1 transcription and latency are crucial to
develop alternate treatment strategies, which impact upon the reservoir and
provide a path toward a "functional cure" in which there is no detectable viremia
in the absence of cART. Numerous reports have suggested ncRNAs are involved in
regulating viral transcription and latency. This review will discuss the latest
developments in ncRNAs, specifically short interfering (si)RNA and short hairpin
(sh)RNA, targeting molecular mechanisms of HIV-1 transcription, which may
represent potential future therapeutics. It will also briefly address animal
models for testing potential therapeutics and current gene therapy clinical
trials.
PMID- 26441980
TI - Mechanisms of Kidney Injury in Lupus Nephritis - the Role of Anti-dsDNA
Antibodies.
AB - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a
breakdown of self-tolerance, production of auto-antibodies and immune-mediated
injury, resulting in damage accrual in multiple organs. Kidney involvement,
termed lupus nephritis, is a major cause of morbidity and mortality that affects
over half of the SLE population during the course of disease. The etiology of
lupus nephritis is multifactorial and remains to be fully elucidated.
Accumulating evidence suggests that in addition to forming immune complexes and
triggering complement activation, anti-dsDNA antibodies contribute to the
pathogenesis of lupus nephritis through binding, either directly or indirectly,
to cross-reactive antigens or chromatin materials, respectively, to resident
renal cells and/or extracellular matrix components, thereby triggering downstream
cellular activation and proliferation as well as inflammatory and fibrotic
processes. Several cross-reactive antigens that mediate anti-dsDNA antibody
binding have been identified, such as annexin II and alpha-actinin. This review
discusses the mechanisms through which anti-dsDNA antibodies contribute to
immunopathogenesis in lupus nephritis. Corticosteroids combined with either
mycophenolic acid (MPA) or cyclophosphamide is the current standard of care
immunosuppressive therapy for severe lupus nephritis. This review also discusses
recent data showing distinct effects of MPA and cyclophosphamide on inflammatory
and fibrotic processes in resident renal cells.
PMID- 26441981
TI - A Dataset of 26 Candidate Gene and Pro-Inflammatory Cytokine Variants for
Association Studies in Idiopathic Pulmonary Fibrosis: Frequency Distribution in
Normal Czech Population.
PMID- 26441983
TI - S100A9 Tetramers, Which are Ligands of CD85j, Increase the Ability of MVAHIV
Primed NK Cells to Control HIV Infection.
AB - Natural killer (NK) cells are the major antiviral effector population of the
innate immune system. We previously found that S100A9 is a novel ligand of the
receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK
cells. Also, we found that dendritic cells (DCs) infected by the HIV vaccine
candidate, MVAHIV, prime NK cells to specifically control HIV infection in
autologous CD4(+) T cells. In this study, we analyzed whether stimulation of NK
cells by S100A9 tetramers prior to the priming by MVAHIV-infected DCs modulates
the subsequent anti-HIV activity of NK cells. We found that S100A9 tetramers
activate NK cells and that DCs enhance the anti-HIV activity of NK cells.
Interestingly, we observed that stimulation of NK cells by S100A9 tetramers,
prior to the priming, significantly increased the subsequent anti-HIV activity of
NK cells and that the enhanced anti-HIV activity was observed following different
conditions of priming, including the MVAHIV-priming. As S100A9 tetramers alone
directly increase the anti-HIV activity of NK cells and as this increased anti
HIV activity is also observed following the interaction of NK cells with MVAHIV
infected DCs, we propose S100A9 tetramers as potential adjuvants to stimulate the
anti-HIV activity of NK cells.
PMID- 26441982
TI - Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for
Cardiovascular Disease.
AB - Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed protease that regulates
diverse number of physiological functions. As a dipeptidase, it exerts its
catalytic effects on proteins/peptides with proline, alanine, or serine in the
penultimate (P1) amino acid residue from the amino terminus. The evidence to date
supports an important effect of DPP4 in catalytic cleavage of incretin peptides
and this perhaps represents the main mechanism by which DPP4 inhibition improves
glycemic control. DPP4 also plays an important role in the degradation of
multiple chemokines of which stromal cell-derived factor-1 (SDF-1, also known as
CXCL12) is perhaps an increasingly recognized target, given its importance in
processes, such as hematopoiesis, angiogenesis, and stem cell homing. In the
current review, we will summarize the importance of DPP4-mediated enzymatic
processing of cytokines/chemokines with an emphasis on SDF-1 and resultant
implications for cardiovascular physiology and disease.
PMID- 26441984
TI - Splenic Macrophage Subsets and Their Function during Blood-Borne Infections.
AB - The spleen is one of the major immunological sites for maintaining blood
homeostasis. Previous studies showed that heterogeneous splenic macrophage
populations contribute in complimentary ways to control blood-borne infections
and induce effective immune responses. Marginal metallophilic macrophages
(MMMPhis) and marginal zone macrophages (MZMPhis) are cells with great ability to
internalize blood-borne pathogens such as virus or bacteria. Their localization
adjacent to T- and B-cell-rich splenic areas favors the rapid contact between
these macrophages and cells from adaptive immunity. Indeed, MMMPhis and MZMPhis
are considered important bridges between innate and adaptive immunity. Although
red pulp macrophages (RpMPhis) are mainly considered scavengers for senescent
erythrocytes, several data indicate a role for RpMPhis in control of infections
such as blood-stage malaria as well as in the induction of innate and adaptive
immunity. Here, we review current data on how different macrophage subsets
recognize and help eliminate blood-borne pathogens, and, in turn, how the
inflammatory microenvironment in different phases of infection (acute, chronic,
and after pathogen clearance) influences macrophage function and survival.
PMID- 26441985
TI - Editorial: Pattern Recognition Receptors and Cancer.
PMID- 26441986
TI - Critical Role of Tumor Microenvironment in Shaping NK Cell Functions: Implication
of Hypoxic Stress.
AB - Blurring the boundary between innate and adaptive immune system, natural killer
(NK) cells, a key component of the innate immunity, are recognized as potent
anticancer mediators. Extensive studies have been detailed on how NK cells get
activated and recognize cancer cells. In contrast, few studies have been focused
on how tumor microenvironment-mediated immunosubversion and immunoselection of
tumor-resistant variants may impair NK cell function. Accumulating evidences
indicate that several cell subsets (macrophages, myeloid-derived suppressive
cells, T regulatory cells, dendritic cells, cancer-associated fibroblasts, and
tumor cells), their secreted factors, as well as metabolic components (i.e.,
hypoxia) have immunosuppressive roles in the tumor microenvironment and are able
to condition NK cells to become anergic. In this review, we will describe how NK
cells react with different stromal cells in the tumor microenvironment. This will
be followed by a discussion on the role of hypoxic stress in the regulation of NK
cell functions. The aim of this review is to provide a better understanding of
how the tumor microenvironment impairs NK cell functions, thereby limiting the
use of NK cell-based therapy, and we will attempt to suggest more efficient tools
to establish a more favorable tumor microenvironment to boost NK cell
cytotoxicity and control tumor progression.
PMID- 26441987
TI - CD74 in Kidney Disease.
AB - CD74 (invariant MHC class II) regulates protein trafficking and is a receptor for
macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d
DT/MIF-2). CD74 expression is increased in tubular cells and/or glomerular
podocytes and parietal cells in human metabolic nephropathies, polycystic kidney
disease, graft rejection and kidney cancer and in experimental diabetic
nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose,
lyso-Gb3) levels and inflammatory cytokines increase kidney cell CD74. MIF
activates CD74 to increase inflammatory cytokines in podocytes and tubular cells
and proliferation in glomerular parietal epithelial cells and cyst cells. MIF
overexpression promotes while MIF targeting protects from experimental glomerular
injury and kidney cysts, and interference with MIF/CD74 signaling or CD74
deficiency protected from crescentic glomerulonephritis. However, CD74 may
protect from interstitial kidney fibrosis. Furthermore, CD74 expression by
stressed kidney cells raises questions about the kidney safety of cancer therapy
strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus,
understanding CD74 biology in kidney cells is relevant for kidney therapeutics.
PMID- 26441988
TI - Mathematical Modeling of Early Cellular Innate and Adaptive Immune Responses to
Ischemia/Reperfusion Injury and Solid Organ Allotransplantation.
AB - A mathematical model of the early inflammatory response in transplantation is
formulated with ordinary differential equations. We first consider the
inflammatory events associated only with the initial surgical procedure and the
subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host
as well as the donor graft. These events release damage-associated molecular
pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In
simulations of this model, resolution of inflammation depends on the severity of
the tissue damage caused by these events and the patient's (co)-morbidities. We
augment a portion of a previously published mathematical model of acute
inflammation with the inflammatory effects of T cells in the absence of antigenic
allograft mismatch (but with DAMP release proportional to the degree of graft
damage prior to transplant). Finally, we include the antigenic mismatch of the
graft, which leads to the stimulation of potent memory T cell responses, leading
to further DAMP release from the graft and concomitant increase in allograft
damage. Regulatory mechanisms are also included at the final stage. Our
simulations suggest that surgical injury and I/R-induced graft damage can be well
tolerated by the recipient when each is present alone, but that their combination
(along with antigenic mismatch) may lead to acute rejection, as seen clinically
in a subset of patients. An emergent phenomenon from our simulations is that low
level DAMP release can tolerize the recipient to a mismatched allograft, whereas
different restimulation regimens resulted in an exaggerated rejection response,
in agreement with published studies. We suggest that mechanistic mathematical
models might serve as an adjunct for patient- or sub-group-specific predictions,
simulated clinical studies, and rational design of immunosuppression.
PMID- 26441989
TI - Gut-Associated Plasmacytoid Dendritic Cells Display an Immature Phenotype and
Upregulated Granzyme B in Subjects with HIV/AIDS.
AB - Plasmacytoid dendritic cells (pDCs) in the periphery of subjects with human
immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) decrease
over time, and the fate of these cells has been the subject of ongoing
investigation. Previous studies using animal models as well as studies with
humans suggest that these cells may redistribute to the gut. Other studies using
animal models propose that the periphery pDCs are depleted and gut is repopulated
with naive pDCs from the bone marrow. In the present study, we utilized
immunohistochemistry to survey duodenum biopsies of subjects with HIV/AIDS and
controls. We observed that subjects with HIV/AIDS had increased infiltration of
Ki-67(+)/CD303(+) pDCs, a phenotype consistent with bone marrow-derived pre-pDCs.
In contrast, Ki-67(+)/CD303(+) pDCs were not observed in control biopsies. We
additionally observed that gut-associated pDCs in HIV/AIDS cases upregulate the
proapoptotic enzyme granzyme B; however, no granzyme B was observed in the pDCs
of control biopsies. Our data are consistent with reports in animal models that
suggest periphery pDCs are depleted by exhaustion and that naive pDCs egress from
the bone marrow and ultimately infiltrate the gut mucosa. Additionally, our
observation of granzyme B upregulation in naive pDCs may identify a contributing
factor to the gut pathology associated with HIV infection.
PMID- 26441990
TI - Ontogeny of Tissue-Resident Macrophages.
AB - The origin of tissue-resident macrophages, crucial for homeostasis and immunity,
has remained controversial until recently. Originally described as part of the
mononuclear phagocyte system, macrophages were long thought to derive solely from
adult blood circulating monocytes. However, accumulating evidence now shows that
certain macrophage populations are in fact independent from monocyte and even
from adult bone marrow hematopoiesis. These tissue-resident macrophages derive
from sequential seeding of tissues by two precursors during embryonic
development. Primitive macrophages generated in the yolk sac (YS) from early
erythro-myeloid progenitors (EMPs), independently of the transcription factor c
Myb and bypassing monocytic intermediates, first give rise to microglia. Later,
fetal monocytes, generated from c-Myb(+) EMPs that initially seed the fetal liver
(FL), then give rise to the majority of other adult macrophages. Thus,
hematopoietic stem cell-independent embryonic precursors transiently present in
the YS and the FL give rise to long-lasting self-renewing macrophage populations.
PMID- 26441991
TI - Functional Role of G9a Histone Methyltransferase in Cancer.
AB - Post-translational modifications of DNA and histones are epigenetic mechanisms,
which affect the chromatin structure, ultimately leading to gene expression
changes. A number of different epigenetic enzymes are actively involved in the
addition or the removal of various covalent modifications, which include
acetylation, methylation, phosphorylation, ubiquitination, and sumoylation.
Deregulation of these processes is a hallmark of cancer. For instance, G9a, a
histone methyltransferase responsible for histone H3 lysine 9 (H3K9) mono- and
dimethylation, has been observed to be upregulated in different types of cancer
and its overexpression has been associated with poor prognosis. Key roles played
by these enzymes in various diseases have led to the hypothesis that these
molecules represent valuable targets for future therapies. Several small molecule
inhibitors have been developed to specifically block the epigenetic activity of
these enzymes, representing promising therapeutic tools in the treatment of human
malignancies, such as cancer. In this review, the role of one of these epigenetic
enzymes, G9a, is discussed, focusing on its functional role in regulating gene
expression as well as its implications in cancer initiation and progression. We
also discuss important findings from recent studies using epigenetic inhibitors
in cell systems in vitro as well as experimental tumor growth and metastasis
assays in vivo.
PMID- 26441992
TI - Therapeutic Potential of Hyporesponsive CD4(+) T Cells in Autoimmunity.
AB - The interaction between dendritic cells (DCs) and T cells is crucial on immunity
or tolerance induction. In an immature or semi-mature state, DCs induce tolerance
through T-cell deletion, generation of regulatory T cells, and/or induction of T
cell anergy. Anergy is defined as an unresponsive state that retains T cells in
an "off" mode under conditions in which immune activation is undesirable. This
mechanism is crucial for the control of T-cell responses against self-antigens,
thereby preventing autoimmunity. Tolerogenic DCs (tDCs), generated in vitro from
peripheral blood monocytes of healthy donors or patients with autoimmune
pathologies, were shown to modulate immune responses by inducing T-cell
hyporesponsiveness. Animal models of autoimmune diseases confirmed the impact of
T-cell anergy on disease development and progression in vivo. Thus, the induction
of T-cell hyporesponsiveness by tDCs has become a promising immunotherapeutic
strategy for the treatment of T-cell-mediated autoimmune disorders. Here, we
review recent findings in the area and discuss the potential of anergy induction
for clinical purposes.
PMID- 26441993
TI - Intestinal Microbiota and the Innate Immune System - A Crosstalk in Crohn's
Disease Pathogenesis.
AB - Crohn's disease (CD) is a chronic, relapsing inflammatory disorder that can occur
anywhere along the gastrointestinal tract. The precise etiology of CD is still
unclear but it is widely accepted that a complex series of interactions between
susceptibility genes, the immune system and environmental factors are implicated
in the onset and perpetuation of the disease. Increasing evidence from
experimental and clinical studies implies the intestinal microbiota in disease
pathogenesis, thereby supporting the hypothesis that chronic intestinal
inflammation arises from an abnormal immune response against the microorganisms
of the intestinal flora in genetically susceptible individuals. Given that CD
patients display changes in their gut microbiota composition, collectively termed
"dysbiosis," the question raises whether the altered microbiota composition is a
cause of disease or rather a consequence of the inflammatory state of the
intestinal environment. This review will focus on the crosstalk between the gut
microbiota and the innate immune system during intestinal inflammation, thereby
unraveling the role of the microbiota in CD pathogenesis.
PMID- 26441994
TI - Inulin-Type beta2-1 Fructans have Some Effect on the Antibody Response to
Seasonal Influenza Vaccination in Healthy Middle-Aged Humans.
AB - beta2-1 fructans are prebiotics and, as such, may modulate some aspects of immune
function. Improved immune function could enhance the host's ability to respond to
infections. There is limited information on the effects of beta2-1 fructans on
immune responses in humans. The objective of the study was to determine the
effect of a specific combination of long-chain inulin and oligofructose
(Orafti((r)) Synergy1) on immune function in middle-aged humans, with the primary
outcome being response to seasonal influenza vaccination. Healthy middle-aged
humans (45-63 years of age) were randomly allocated to consume beta2-1 fructans
in the form of Orafti((r)) Synergy1 (8 g/day; n = 22) or maltodextrin as control
(8 g/day; n = 21) for 8 weeks. After 4 weeks, participants received the 2008/2009
seasonal influenza vaccine. Blood and saliva samples were collected prior to
vaccination and 2 and 4 weeks after vaccination. They were used to measure
various immune parameters. The primary outcome was the serum concentration of
anti-vaccine antibodies. Serum antibody titers against the vaccine and vaccine
specific immunoglobulin concentrations increased post-vaccination. Antibodies to
the H3N2-like hemagglutinin type 3, neuraminidase type 2-like strain were higher
in the Synergy1 group (P = 0.020 for overall effect of treatment group), as was
serum vaccine-specific IgG1 2 weeks post-vaccination (P = 0.028 versus control).
There were no other differences between groups in antibody titers or anti-vaccine
immunoglobulin concentrations, in blood immune cell phenotypes, or in a range of
immune parameters. It is concluded that Orafti((r)) Synergy1, a combination of
beta2-1 fructans, can enhance some aspects of the immune response in healthy
middle-aged adults, but that this is not a global effect.
PMID- 26441995
TI - Editorial: Antimicrobial Peptides and Complement - Maximising the Inflammatory
Response.
PMID- 26441998
TI - An improved high-throughput screening assay for tunicamycin sensitivity in
Arabidopsis seedlings.
AB - Tunicamycin (Tm) sensitivity assays are a useful method for studies of
endoplasmic reticulum stress and the unfolded protein response in eukaryotic
cells. While Tm sensitivity and Tm recovery assays have been previously
described, these existing methods are time-consuming, labor intensive, and
subjected to mechanical wounding. This study shows an improved method of testing
Tm sensitivity in Arabidopsis using liquid Murashige and Skoog medium versus the
traditional solid agar plates. Liquid medium bypasses the physical manipulation
of seedlings, thereby eliminating the risk of potential mechanical damage and
additional unwanted stress to seedlings. Seedlings were subjected to comparative
treatments with various concentrations of Tm on both solid and liquid media and
allowed to recover. Determination of fresh weight, chlorophyll contents analysis
and qRT-PCR results confirm the efficacy of using liquid medium to perform
quantitative Tm stress assays.
PMID- 26441997
TI - NKp46 Clusters at the Immune Synapse and Regulates NK Cell Polarization.
AB - Natural killer (NK) cells play an important role in first-line defense against
tumor and virus-infected cells. The activity of NK cells is tightly regulated by
a repertoire of cell surface expressed inhibitory and activating receptors. NKp46
is a major NK cell-activating receptor that is involved in the elimination of
target cells. NK cells form different types of synapses that result in distinct
functional outcomes: cytotoxic, inhibitory, and regulatory. Recent studies
revealed that complex integration of NK receptor signaling controls cytoskeletal
rearrangement and other immune synapse-related events. However, the distinct
nature by which NKp46 participates in NK immunological synapse formation and
function remains unknown. In this study, we determined that NKp46 forms
microclusters structures at the immune synapse between NK cells and target cells.
Over-expression of human NKp46 is correlated with increased accumulation of F
actin mesh at the immune synapse. Concordantly, knock-down of NKp46 in primary
human NK cells decreased recruitment of F-actin to the synapse. Live cell imaging
experiments showed a linear correlation between NKp46 expression and lytic
granules polarization to the immune synapse. Taken together, our data suggest
that NKp46 signaling directly regulates the NK lytic immune synapse from early
formation to late function.
PMID- 26441996
TI - FOXP3(+) Treg Cells and Gender Bias in Autoimmune Diseases.
AB - CD4(+)CD25(+) regulatory T (Treg) cells play a pivotal role in the maintenance of
immune homeostasis, where the X-linked master transcription factor forkhead box
P3 (FOXP3) determines Treg cell development and function. Genetic deficiency of
foxp3 induces dysfunction of Treg cells and immuno-dysregulation,
polyendocrinopathy, enteropathy, and X-linked syndrome in humans. Functionally
deficient Treg cells or the development of exTreg cells positively correlate with
autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple
sclerosis (MS), and ankylosing spondylitis (AS). In general, females are more
susceptible to SLE and MS but less susceptible to AS, where the expression of
FOXP3 and its protein complex are perturbed by multiple factors, including
hormonal fluctuations, inflammatory cytokines, and danger signals. Therefore, it
is critical to explore the potential molecular mechanisms involved and these
differences linked to gender. Here, we review recent findings on the regulation
of FOXP3 activity in Treg cells and also discuss gender difference in the
determination of Treg cell function in autoimmune diseases.
PMID- 26441999
TI - Colonization of root cells and plant growth promotion by Piriformospora indica
occurs independently of plant common symbiosis genes.
AB - Arbuscular mycorrhiza (AM) fungi (Glomeromycota) form symbiosis with and deliver
nutrients via the roots of most angiosperms. AM fungal hyphae are taken up by
living root epidermal cells, a program which relies on a set of plant common
symbiosis genes (CSGs). Plant root epidermal cells are also infected by the plant
growth-promoting fungus Piriformospora indica (Basidiomycota), raising the
question whether this interaction relies on the AM-related CSGs. Here we show
that intracellular colonization of root cells and intracellular sporulation by P.
indica occurred in CSG mutants of the legume Lotus japonicus and in Arabidopsis
thaliana, which belongs to the Brassicaceae, a family that has lost the ability
to form AM as well as a core set of CSGs. A. thaliana mutants of homologs of CSGs
(HCSGs) interacted with P. indica similar to the wild-type. Moreover, increased
biomass of A. thaliana evoked by P. indica was unaltered in HCSG mutants. We
conclude that colonization and growth promotion by P. indica are independent of
the CSGs and that AM fungi and P. indica exploit different host pathways for
infection.
PMID- 26442000
TI - NAC transcription factor family genes are differentially expressed in rice during
infections with Rice dwarf virus, Rice black-streaked dwarf virus, Rice grassy
stunt virus, Rice ragged stunt virus, and Rice transitory yellowing virus.
AB - Expression levels of the NAC gene family were studied in rice infected with Rice
dwarf virus (RDV), Rice black-streaked dwarf virus (RBSDV), Rice grassy stunt
virus (RGSV), Rice ragged stunt virus (RRSV), and Rice transitory yellowing virus
(RTYV). Microarray analysis showed that 75 (68%) OsNAC genes were differentially
regulated during infection with RDV, RBSDV, RGSV, and RRSV compared with the
control. The number of OsNAC genes up-regulated was highest during RGSV
infection, while the lowest number was found during RTYV infection. These
phenomena correlate with the severity of the syndromes induced by the virus
infections. Most of the genes in the NAC subgroups NAC22, SND, ONAC2, ANAC34, and
ONAC3 were down-regulated for all virus infections. These OsNAC genes might be
related to the health stage maintenance of the host plants. Interestingly, most
of the genes in the subgroups TIP and SNAC were more highly expressed during
RBSDV and RGSV infections. These results suggested that OsNAC genes might be
related to the responses induced by the virus infection. All of the genes
assigned to the TIP subgroups were highly expressed during RGSV infection when
compared with the control. For RDV infection, the number of activated genes was
greatest during infection with the S-strain, followed by the D84-strain and the O
strain, with seven OsNAC genes up-regulated during infection by all three
strains. The Os12g03050 and Os11g05614 genes showed higher expression during
infection with four of the five viruses, and Os11g03310, Os11g03370, and
Os07g37920 genes showed high expression during at least three viral infections.
We identified some duplicate genes that are classified as neofunctional and
subfunctional according to their expression levels in different viral infections.
A number of putative cis-elements were identified, which may help to clarify the
function of these key genes in network pathways.
PMID- 26442001
TI - Expression profiling and functional analysis reveals that TOR is a key player in
regulating photosynthesis and phytohormone signaling pathways in Arabidopsis.
AB - Target of rapamycin (TOR) acts as a master regulator to control cell growth by
integrating nutrient, energy, and growth factors in all eukaryotic species. TOR
plays an evolutionarily conserved role in regulating the transcription of genes
associated with anabolic and catabolic processes in Arabidopsis, but little is
known about the functions of TOR in photosynthesis and phytohormone signaling,
which are unique features of plants. In this study, AZD8055 (AZD) was screened as
the strongest active-site TOR inhibitor (asTORi) in Arabidopsis compared with
TORIN1 and KU63794 (KU). Gene expression profiles were evaluated using RNA-seq
after treating Arabidopsis seedlings with AZD. More than three-fold
differentially expressed genes (DEGs) were identified in AZD-treated plants
relative to rapamycin-treated plants in previous studies. Most of the DEGs and
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in cell wall
elongation, ribosome biogenesis, and cell autophagy were common to both AZD- and
rapamycin-treated samples, but AZD displayed much broader and more efficient
inhibition of TOR compared with rapamycin. Importantly, the suppression of TOR by
AZD resulted in remodeling of the expression profile of the genes associated with
photosynthesis and various phytohormones, indicating that TOR plays a crucial
role in modulating photosynthesis and phytohormone signaling in Arabidopsis.
These newly identified DEGs expand the understanding of TOR signaling in plants.
This study elucidates the novel functions of TOR in photosynthesis and
phytohormone signaling and provides a platform to study the downstream targets of
TOR in Arabidopsis.
PMID- 26442003
TI - Effects of different carbohydrate sources on fructan metabolism in plants of
Chrysolaena obovata grown in vitro.
AB - Chrysolaena obovata (Less.) Dematt., previously named Vernonia herbacea, is an
Asteraceae native to the Cerrado which accumulates about 80% of the rhizophore
dry mass as inulin-type fructans. Considering its high inulin production and the
wide application of fructans, a protocol for C. obovata in vitro culture was
recently established. Carbohydrates are essential for in vitro growth and
development of plants and can also act as signaling molecules involved in
cellular adjustments and metabolic regulation. This work aimed to evaluate the
effect of different sources of carbohydrate on fructan metabolism in plants grown
in vitro. For this purpose, C. obovata plants cultivated in vitro were submitted
to carbon deprivation and transferred to MS medium supplemented with sucrose,
glucose or fructose. Following, their fructan composition and activity and
expression of genes encoding enzymes for fructan synthesis (1-SST and 1-FFT) and
degradation (1-FEH) were evaluated. For qRT-PCR analysis partial cDNA sequences
corresponding to two different C. obovata genes, 1-SST and 1-FFT, were isolated.
As expected, C. obovata sequences showed highest sequence identity to other
Asteraceae 1-SST and 1-FFT, than to Poaceae related proteins. A carbon deficit
treatment stimulated the transcription of the gene 1-FEH and inhibited 1-SST and
1-FFT and carbohydrate supplementation promoted reversal of the expression
profile of these genes. With the exception of 1-FFT, a positive correlation
between enzyme activity and gene expression was observed. The overall results
indicate that sucrose, fructose and glucose act similarly on fructan metabolism
and that 1-FEH and 1-SST are transcriptionally regulated by sugar in this
species. Cultivation of plants in increasing sucrose concentrations stimulated
synthesis and inhibited fructan mobilization, and induced a distinct pattern of
enzyme activity for 1-SST and 1-FFT, indicating the existence of a mechanism for
differential regulation between them.
PMID- 26442002
TI - Transcriptomic analysis reveals importance of ROS and phytohormones in response
to short-term salinity stress in Populus tomentosa.
AB - Populus tomentosa (Chinese white poplar) is well adapted to various extreme
environments, and is considered an important species to study the effects of
salinity stress on poplar trees. To decipher the mechanism of poplar's rapid
response to short-term salinity stress, we firstly detected the changes in H2O2
and hormone, and then profiled the gene expression pattern of 10-week-old
seedling roots treated with 200 mM NaCl for 0, 6, 12, and 24 h (h) by RNA-seq on
the Illumina-Solexa platform. Physiological determination showed that the
significant increase in H2O2 began at 6 h, while that in hormone ABA was at 24 h,
under salt stress. Compared with controls (0 h), 3991, 4603, and 4903 genes were
up regulated, and 1408, 2206, and 3461 genes were down regulated (adjusted P <=
0.05 and |log2Ratio|>=1) at 6, 12, and 24 h time points, respectively. The Gene
Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
annotation revealed that the differentially expressed genes (DEGs) were highly
enriched in hormone- and reactive oxygen species-related biological processes,
including "response to oxidative stress or abiotic stimulus," "peroxidase
activity," "regulation of transcription," "hormone synthetic and metabolic
process," "hormone signal transduction," "antioxidant activity," and
"transcription factor activity." Moreover, K-means clustering demonstrated that
DEGs (total RPKM value>12 from four time points) could be categorized into four
kinds of expression trends: quick up/down over 6 or 12 h, and slow up/down over
24 h. Of these, DEGs involved in H2O2- and hormone- producing and signal-related
genes were further enriched in this analysis, which indicated that the two kinds
of small molecules, hormones and H2O2, play pivotal roles in the short-term salt
stress response in poplar. This study provides a basis for future studies of the
molecular adaptation of poplar and other tree species to salinity stress.
PMID- 26442004
TI - Expression of chickpea CIPK25 enhances root growth and tolerance to dehydration
and salt stress in transgenic tobacco.
AB - Calcium signaling plays an important role in adaptation and developmental
processes in plants and animals. A class of calcium sensors, known as Calcineurin
B-like (CBL) proteins sense specific temporal changes in cytosolic Ca(2+)
concentration and regulate activities of a group of ser/thr protein kinases
called CBL-interacting protein kinases (CIPKs). Although a number of CIPKs have
been shown to play crucial roles in the regulation of stress signaling, no study
on the function of CIPK25 or its orthologs has been reported so far. In the
present study, an ortholog of Arabidopsis CIPK25 was cloned from chickpea (Cicer
arietinum). CaCIPK25 gene expression in chickpea increased upon salt,
dehydration, and different hormonal treatments. CaCIPK25 gene showed differential
tissue-specific expression. 5'-upstream activation sequence (5'-UAS) of the gene
and its different truncated versions were fused to a reporter gene and studied in
Arabidopsis to identify promoter regions directing its tissue-specific
expression. Replacement of a conserved threonine residue with an aspartic acid at
its catalytic site increased the kinase activity of CaCIPK25 by 2.5-fold.
Transgenic tobacco plants overexpressing full-length and the high active versions
of CaCIPK25 displayed a differential germination period and longer root length in
comparison to the control plants. Expression of CaCIPK25 and its high active form
differentially increased salt and water-deficit tolerance demonstrated by
improved growth and reduced leaf chlorosis suggesting that the kinase activity of
CaCIPK25 was required for these functions. Expressions of the abiotic stress
marker genes were enhanced in the CaCIPK25-expressing tobacco plants. Our results
suggested that CaCIPK25 functions in root development and abiotic stress
tolerance.
PMID- 26442005
TI - Agave as a model CAM crop system for a warming and drying world.
AB - As climate change leads to drier and warmer conditions in semi-arid regions,
growing resource-intensive C3 and C4 crops will become more challenging. Such
crops will be subjected to increased frequency and intensity of drought and heat
stress. However, agaves, even more than pineapple (Ananas comosus) and prickly
pear (Opuntia ficus-indica and related species), typify highly productive plants
that will respond favorably to global warming, both in natural and cultivated
settings. With nearly 200 species spread throughout the U.S., Mexico, and Central
America, agaves have evolved traits, including crassulacean acid metabolism
(CAM), that allow them to survive extreme heat and drought. Agaves have been used
as sources of food, beverage, and fiber by societies for hundreds of years. The
varied uses of Agave, combined with its unique adaptations to environmental
stress, warrant its consideration as a model CAM crop. Besides the damaging
cycles of surplus and shortage that have long beset the tequila industry, the
relatively long maturation cycle of Agave, its monocarpic flowering habit, and
unique morphology comprise the biggest barriers to its widespread use as a crop
suitable for mechanized production. Despite these challenges, agaves exhibit
potential as crops since they can be grown on marginal lands, but with more
resource input than is widely assumed. If these constraints can be reconciled,
Agave shows considerable promise as an alternative source for food, alternative
sweeteners, and even bioenergy. And despite the many unknowns regarding agaves,
they provide a means to resolve disparities in resource availability and needs
between natural and human systems in semi-arid regions.
PMID- 26442006
TI - Influence of Rhizoctonia solani and Trichoderma spp. in growth of bean (Phaseolus
vulgaris L.) and in the induction of plant defense-related genes.
AB - Many Trichoderma species are well-known for their ability to promote plant growth
and defense. We study how the interaction of bean plants with R. solani and/or
Trichoderma affect the plants growth and the level of expression of defense
related genes. Trichoderma isolates were evaluated in vitro for their potential
to antagonize R. solani. Bioassays were performed in climatic chambers and
development of the plants was evaluated. The effect of Trichoderma treatment
and/or R. solani infection on the expression of bean defense-related genes was
analyzed by real-time PCR and the production of ergosterol and squalene was
quantified. In vitro growth inhibition of R. solani was between 86 and 58%. In in
vivo assays, the bean plants treated with Trichoderma harzianum T019 always had
an increased size respect to control and the plants treated with this isolate did
not decrease their size in presence of R. solani. The interaction of plants with
R. solani and/or Trichoderma affects the level of expression of seven defense
related genes. Squalene and ergosterol production differences were found among
the Trichoderma isolates, T019 showing the highest values for both compounds. T.
harzianum T019 shows a positive effect on the level of resistance of bean plants
to R. solani. This strain induces the expression of plant defense-related genes
and produces a higher level of ergosterol, indicating its ability to grow at a
higher rate in the soil, which would explain its positive effects on plant growth
and defense in the presence of the pathogen.
PMID- 26442007
TI - The polyamine spermine induces the unfolded protein response via the MAPK cascade
in Arabidopsis.
AB - In Arabidopsis three basic region leucine zipper (bZIP) transcription factor
genes, bZIP17, bZIP28, and bZIP60, play crucial roles in the unfolded protein
response (UPR). Previously we found that bZIP60 is one of the spermine-induced
genes. Consequently we further investigated the response of all the three bZIP
genes to spermine. Expression of bZIP17, bZIP28, and bZIP60, and also their
target genes was activated by spermine application as well as in plants with
elevated endogenous spermine levels. Furthermore, spermine activated the splicing
of the bZIP60 transcript mediated by the ribonuclease activity of inositol
requiring enzyme 1 and also recruited bZIP17 and bZIP60 proteins from endoplasmic
reticulum to nucleus. We therefore propose that spermine is a novel UPR inducer.
Moreover, induction of UPR by spermine required calcium-influx to the cytoplasm
and the genes for mitogen-activated protein kinase kinase 9 (MKK9), mitogen
activated protein kinase 3 (MPK3) and MPK6. The result indicates that spermine
induced UPR is mediated by the MKK9-MPK3/MPK6 cascade in Arabidopsis.
PMID- 26442008
TI - A case study on the genetic origin of the high oleic acid trait through FAD2-1
DNA sequence variation in safflower (Carthamus tinctorius L.).
AB - The safflower (Carthamus tinctorius L.) is considered a strongly domesticated
species with a long history of cultivation. The hybridization of safflower with
its wild relatives has played an important role in the evolution of cultivars and
is of particular interest with regards to their production of high quality edible
oils. Original safflower varieties were all rich in linoleic acid, while
varieties rich in oleic acid have risen to prominence in recent decades. The high
oleic acid trait is controlled by a partially recessive allele ol at a single
locus OL. The ol allele was found to be a defective microsomal oleate desaturase
FAD2-1. Here we present DNA sequence data and Southern blot analysis suggesting
that there has been an ancient hybridization and introgression of the FAD2-1 gene
into C. tinctorius from its wild relative C. palaestinus. It is from this gene
that FAD2-1Delta was derived more recently. Identification and characterization
of the genetic origin and diversity of FAD2-1 could aid safflower breeders in
reducing population size and generations required for the development of new high
oleic acid varieties by using perfect molecular marker-assisted selection.
PMID- 26442009
TI - Biogeography of photoautotrophs in the high polar biome.
AB - The global latitudinal gradient in biodiversity weakens in the high polar biome
and so an alternative explanation for distribution of Arctic and Antarctic
photoautotrophs is required. Here we identify how temporal, microclimate and
evolutionary drivers of biogeography are important, rather than the macroclimate
features that drive plant diversity patterns elsewhere. High polar ecosystems are
biologically unique, with a more central role for bryophytes, lichens and
microbial photoautotrophs over that of vascular plants. Constraints on vascular
plants arise mainly due to stature and ontogenetic barriers. Conversely non
vascular plant and microbial photoautotroph distribution is correlated with
favorable microclimates and the capacity for poikilohydric dormancy. Contemporary
distribution also depends on evolutionary history, with adaptive and dispersal
traits as well as legacy influencing biogeography. We highlight the relevance of
these findings to predicting future impacts on diversity of polar photoautotrophs
and to the current status of plants in Arctic and Antarctic conservation policy
frameworks.
PMID- 26442010
TI - Epigenetic silencing in transgenic plants.
AB - Epigenetic silencing is a natural phenomenon in which the expression of genes is
regulated through modifications of DNA, RNA, or histone proteins. It is a
mechanism for defending host genomes against the effects of transposable elements
and viral infection, and acts as a modulator of expression of duplicated gene
family members and as a silencer of transgenes. A major breakthrough in
understanding the mechanism of epigenetic silencing was the discovery of
silencing in transgenic tobacco plants due to the interaction between two
homologous promoters. The molecular mechanism of epigenetic mechanism is highly
complicated and it is not completely understood yet. Two different molecular
routes have been proposed for this, that is, transcriptional gene silencing,
which is associated with heavy methylation of promoter regions and blocks the
transcription of transgenes, and post-transcriptional gene silencing (PTGS), the
basic mechanism is degradation of the cytosolic mRNA of transgenes or endogenous
genes. Undesired transgene silencing is of major concern in the transgenic
technologies used in crop improvement. A complete understanding of this
phenomenon will be very useful for transgenic applications, where silencing of
specific genes is required. The current status of epigenetic silencing in
transgenic technology is discussed and summarized in this mini-review.
PMID- 26442012
TI - Cryotolerance of apple tree bud is independent of endodormancy.
AB - Increasing interest in cryopreservation of dormant buds reveals the need for
better understanding of the role of dormancy in cryotolerance. Dormancy stage and
low-temperature survival of vegetative apple buds (Malus domestica Borkh.),
cultivars 'Sampion' and 'Spartan', collected from orchard were evaluated during
three seasons contrasting in temperature and precipitation throughout the
arrested plant growth period. During each season, the cultivars differed either
in the onset of the endodormancy or in the length of the endodormant period. A
simple relation between endodormancy of the buds and their water content was not
detected. The cryosurvival of vegetative apple buds of both cultivars correlated
with their cold hardening without direct regard to their particular phase of
dormancy. The period of the highest bud cryotolerance after low-temperature
exposure overlapped with the endodormant period in some evaluated seasons. Both
cultivars had the highest cryosurvival in December and January. The presented
data were compared with our previous results from a dormancy study of in vitro
apple culture. Endodormancy coincided with the period of successful cryosurvival
of apple buds after liquid nitrogen exposure, but as such, it was not decisive
for their survival and did not limit their successful cryopreservation.
PMID- 26442011
TI - Impacts of strigolactone on shoot branching under phosphate starvation in
chrysanthemum (Dendranthema grandiflorum cv. Jinba).
AB - Chrysanthemum (Dendranthema grandiflorum cv. Jinba) shoot branching is determined
by bud outgrowth during the vegetative growth stage. The degree of axillary bud
outgrowth is highly influenced by environmental conditions, such as nutrient
availability. Here, we demonstrated that phosphorus (Pi) starvation significantly
reduces axillary bud outgrowth in chrysanthemum. A strigolactone (SL)
biosynthesis gene, DgCCD7, was isolated and characterized as an ortholog of
MAX3/DAD3/RMS5/D17. By using ultra-performance liquid chromatography coupled with
mass spectrometry (UPLC-MS), three putative SLs were identified and levels of all
three SLs showed strong increase under Pi starvation conditions. Determinations
of the distribution of SLs and regulation of DgCCD7/8 in response to Pi changes
in root indicate that SL acts systemically. However, temporal expression patterns
of biosynthesis and signaling genes in nodes revealed that Pi starvation causes a
local response of SL pathway. Treatment of node segments with or without auxin
and Pi revealed that in the absence of exogenous auxin, Pi delayed axillary buds
outgrowth and up-regulated local SL pathway genes. These data indicated that an
auxin-SL regulatory loop responded to Pi starvation for delaying bud outgrowth
locally, root biosynthesized SLs were transported acropetally and functioned in
shoot branching inhibition under Pi starvation. We proposed that SLs contributed
to chrysanthemum shoot branching control in response to Pi-limiting conditions in
a systemic way.
PMID- 26442013
TI - Species delimitation, genetic diversity and population historical dynamics of
Cycas diannanensis (Cycadaceae) occurring sympatrically in the Red River region
of China.
AB - Delimitating species boundaries could be of critical importance when evaluating
the species' evolving process and providing guidelines for conservation genetics.
Here, species delimitation was carried out on three endemic and endangered Cycas
species with resembling morphology and overlapped distribution range along the
Red River (Yuanjiang) in China: Cycas diananensis Z. T. Guan et G. D. Tao, Cycas
parvula S. L. Yang and Cycas multiovula D. Y. Wang. A total of 137 individuals
from 15 populations were genotyped by using three chloroplastic (psbA-trnH, atpI
atpH, and trnL-rps4) and two single copy nuclear (RPB1 and SmHP) DNA sequences.
Basing on the carefully morphological comparison and cladistic haplotype
aggregation (CHA) analysis, we propose all the populations as one species, with
the rest two incorporated into C. diannanensis. Genetic diversity and structure
analysis of the conflated C. diannanensis revealed this species possessed a
relative lower genetic diversity than estimates of other Cycas species. The
higher genetic diversity among populations and relative lower genetic diversity
within populations, as well as obvious genetic differentiation among populations
inferred from chloroplastic DNA (cpDNA) suggested a recent genetic loss within
this protected species. Additionally, a clear genetic structure of C.
diannanensis corresponding with geography was detected based on cpDNA, dividing
its population ranges into "Yuanjiang-Nanhun" basin and "Ejia-Jiepai" basin
groups. Demographical history analyses based on combined cpDNA and one nuclear
DNA (nDNA) SmHP both showed the population size of C. diannanensis began to
decrease in Quaternary glaciation with no subsequent expansion, while another
nDNA RPB1 revealed a more recent sudden expansion after long-term population size
contraction, suggesting its probable bottleneck events in history. Our findings
offer grounded views for clarifying species boundaries of C. diannanensis when
determining the conservation objectives. For operational guidelines, the
downstream populations which occupy high and peculiar haplotypes should be given
prior in-situ conservation. In addition, ex-situ conservation and reintroduction
measures for decades of generations are supplemented for improving the population
size and genetic diversity of the endemic and endangered species.
PMID- 26442014
TI - Natural variation in cross-talk between glucosinolates and onset of flowering in
Arabidopsis.
AB - Naturally variable regulatory networks control different biological processes
including reproduction and defense. This variation within regulatory networks
enables plants to optimize defense and reproduction in different environments. In
this study we investigate the ability of two enzyme-encoding genes in the
glucosinolate pathway, AOP2 and AOP3, to affect glucosinolate accumulation and
flowering time. We have introduced the two highly similar enzymes into two
different AOP (null) accessions, Col-0 and Cph-0, and found that the genes differ
in their ability to affect glucosinolate levels and flowering time across the
accessions. This indicated that the different glucosinolates produced by AOP2 and
AOP3 serve specific regulatory roles in controlling these phenotypes. While the
changes in glucosinolate levels were similar in both accessions, the effect on
flowering time was dependent on the genetic background pointing to natural
variation in cross-talk between defense chemistry and onset of flowering. This
variation likely reflects an adaptation to survival in different environments.
PMID- 26442015
TI - Transgenerational inheritance or resetting of stress-induced epigenetic
modifications: two sides of the same coin.
AB - The transgenerational inheritance of stress-induced epigenetic modifications is
still controversial. Despite several examples of defense "priming" and induced
genetic rearrangements, the involvement and persistence of transgenerational
epigenetic modifications is not known to be general. Here I argue that non
transmission of epigenetic marks through meiosis may be regarded as an epigenetic
modification in itself, and that we should understand the implications for plant
evolution in the context of both selection for and selection against
transgenerational epigenetic memory. Recent data suggest that both epigenetic
inheritance and resetting are mechanistically directed and targeted. Stress
induced epigenetic modifications may buffer against DNA sequence-based evolution
to maintain plasticity, or may form part of plasticity's adaptive potential. To
date we have tended to concentrate on the question of whether and for how long
epigenetic memory persists. I argue that we should now re-direct our question to
investigate the differences between where it persists and where it does not, to
understand the higher order evolutionary methods in play and their contribution.
PMID- 26442016
TI - Rhizosphere ecology of lumichrome and riboflavin, two bacterial signal molecules
eliciting developmental changes in plants.
AB - Lumichrome and riboflavin are novel molecules from rhizobial exudates that
stimulate plant growth. Reported studies have revealed major developmental
changes elicited by lumichrome at very low nanomolar concentrations (5 nM) in
plants, which include early initiation of trifoliate leaves, expansion of
unifoliate and trifoliate leaves, increased stem elongation and leaf area, and
consequently greater biomass accumulation in monocots and dicots. But higher
lumichrome concentration (50 nM) depressed root development and reduced growth of
unifoliate and second trifoliate leaves. While the mechanisms remain unknown, it
is possible that lumichrome released by rhizobia induced the biosynthesis of
classical phytohormones that caused the observed developmental changes in plants.
We also showed in earlier studies that applying either 10 nM lumichrome, 10 nM
ABA, or 10 ml of infective rhizobial cells (0.2 OD600) to roots of monocots and
dicots for 44 h produced identical effects, which included decreased stomatal
conductance and leaf transpiration in Bambara groundnut, soybean, and maize,
increased stomatal conductance and transpiration in cowpea and lupin, and
elevated root respiration in maize (19% by rhizobia and 20% by lumichrome).
Greater extracellular exudation of lumichrome, riboflavin and indole acetic acid
by N2-fixing rhizobia over non-fixing bacteria is perceived to be an indication
of their role as symbiotic signals. This is evidenced by the increased
concentration of lumichrome and riboflavin in the xylem sap of cowpea and soybean
plants inoculated with infective rhizobia. In fact, greater xylem concentration
of lumichrome in soybean and its correspondingly increased accumulation in leaves
was found to result in dramatic developmental changes than in cowpea.
Furthermore, lumichrome and riboflavin secreted by soil rhizobia are also known
to function as (i) ecological cues for sensing environmental stress, (ii) growth
factors for microbes, plants, and humans, (iii) signals for stomatal functioning
in land plants, and (iv) protectants/elicitors of plant defense. The fact that
exogenous application of ABA to plant roots caused the same effect as lumichrome
on leaf stomatal functioning suggests molecular cross-talk in plant response to
environmental stimuli.
PMID- 26442018
TI - Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich
motif.
AB - The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly
hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which
accumulate during the late stages of embryogenesis and in response to abiotic
stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N
terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear
localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal
cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular
Fluorescence Complementation (BiFC) approach was demonstrated. In order to
understand the in vivo role of the histidine-rich motif, the OpsDHN1-DeltaHis
version was produced and assayed for its subcellular localization and dimer
capability by GFP fusion and BiFC assays, respectively. We found that deletion of
the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but
did not affect dimer formation. In addition, the deletion of the S-segment in the
OpsDHN1 protein affected its nuclear localization. Our data suggest that the
deletion of histidine-rich motif and S-segment show similar effects, preventing
OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich
motif is proposed as a targeting element for OpsDHN1 nuclear localization.
PMID- 26442017
TI - Response and adaptation of photosynthesis, respiration, and antioxidant systems
to elevated CO2 with environmental stress in plants.
AB - It is well known that plant photosynthesis and respiration are two fundamental
and crucial physiological processes, while the critical role of the antioxidant
system in response to abiotic factors is still a focus point for investigating
physiological stress. Although one key metabolic process and its response to
climatic change have already been reported and reviewed, an integrative review,
including several biological processes at multiple scales, has not been well
reported. The current review will present a synthesis focusing on the underlying
mechanisms in the responses to elevated CO2 at multiple scales, including
molecular, cellular, biochemical, physiological, and individual aspects,
particularly, for these biological processes under elevated CO2 with other key
abiotic stresses, such as heat, drought, and ozone pollution, as well as nitrogen
limitation. The present comprehensive review may add timely and substantial
information about the topic in recent studies, while it presents what has been
well established in previous reviews. First, an outline of the critical
biological processes, and an overview of their roles in environmental regulation,
is presented. Second, the research advances with regard to the individual
subtopics are reviewed, including the response and adaptation of the
photosynthetic capacity, respiration, and antioxidant system to CO2 enrichment
alone, and its combination with other climatic change factors. Finally, the
potential applications for plant responses at various levels to climate change
are discussed. The above issue is currently of crucial concern worldwide, and
this review may help in a better understanding of how plants deal with elevated
CO2 using other mainstream abiotic factors, including molecular, cellular,
biochemical, physiological, and whole individual processes, and the better
management of the ecological environment, climate change, and sustainable
development.
PMID- 26442019
TI - Tree water status and growth of saplings and mature Norway spruce (Picea abies)
at a dry distribution limit.
AB - We evaluated the size effect on stem water status and growth in Norway spruce
(Picea abies (L.) Karst.) occurring at the edge of its natural range in a dry
inner Alpine environment (750 m asl, Tyrol, Austria). Intra-annual dynamics of
stem water deficit (DeltaW), maximum daily shrinkage (MDS), and radial growth
(RG) were compared among saplings (stem diameter/height: 2.2 cm/93 cm; n = 7) and
mature adult trees (25 cm/12.7 m; n = 6) during 2014. DeltaW, MDS, and RG were
extracted from stem diameter variations, which were continuously recorded by
automatic dendrometers and the influence of environmental drivers was evaluated
by applying moving correlation analysis (MCA). Additionally, we used Morlet
wavelet analysis to assess the differences in cyclic radial stem variations
between saplings and mature trees. Results indicate that saplings and mature
trees were experiencing water limitation throughout the growing season. However,
saplings exhibited a more strained stem water status and higher sensitivity to
environmental conditions than mature trees. Hence, the significantly lower radial
increments in saplings (0.16 +/- 0.03 mm) compared to mature trees (0.54 +/- 0.14
mm) is related to more constrained water status in the former, affecting the rate
and duration of RG. The wavelet analysis consistently revealed more distinct
diurnal stem variations in saplings compared to mature trees. Intra-annual RG was
most closely related to climate variables that influence transpiration, i.e.,
vapor pressure deficit, relative air humidity, and air temperature. MCA, however,
showed pronounced instability of climate-growth relationships, which masked
missing temporal or significant correlations when the entire study period (April
October) was considered. We conclude that an increase in evaporative demand will
impair regeneration and long-term stability of drought-prone inner Alpine Norway
spruce forests.
PMID- 26442020
TI - The future of lupin as a protein crop in Europe.
AB - Europe has become heavily dependent on soya bean imports, entailing trade
agreements and quality standards that do not satisfy the European citizen's
expectations. White, yellow, and narrow-leafed lupins are native European legumes
that can become true alternatives to soya bean, given their elevated and high
quality protein content, potential health benefits, suitability for sustainable
production, and acceptability to consumers. Nevertheless, lupin cultivation in
Europe remains largely insufficient to guarantee a steady supply to the food
industry, which in turn must innovate to produce attractive lupin-based protein
rich foods. Here, we address different aspects of the food supply chain that
should be considered for lupin exploitation as a high-value protein source.
Advanced breeding techniques are needed to provide new lupin varieties for socio
economically and environmentally sustainable cultivation. Novel processes should
be optimized to obtain high-quality, safe lupin protein ingredients, and
marketable foods need to be developed and offered to consumers. With such an
integrated strategy, lupins can be established as an alternative protein crop,
capable of promoting socio-economic growth and environmental benefits in Europe.
PMID- 26442021
TI - Ethephon induced abscission in mango: physiological fruitlet responses.
AB - Fruitlet abscission of mango is typically very severe, causing considerable
production losses worldwide. Consequently, a detailed physiological and molecular
characterization of fruitlet abscission in mango is required to describe the
onset and time-dependent course of this process. To identify the underlying key
mechanisms of abscission, ethephon, an ethylene releasing substance, was applied
at two concentrations (600 and 7200 ppm) during the midseason drop stage of
mango. The abscission process is triggered by ethylene diffusing to the
abscission zone where it binds to specific receptors and thereby activating
several key physiological responses at the cellular level. The treatments reduced
significantly the capacity of polar auxin transport through the pedicel at 1 day
after treatment and thereafter when compared to untreated pedicels. The
transcript levels of the ethylene receptor genes MiETR1 and MiERS1 were
significantly upregulated in the pedicel and pericarp at 1, 2, and 3 days after
the ethephon application with 7200 ppm, except for MiETR1 in the pedicel, when
compared to untreated fruitlet. In contrast, ethephon applications with 600 ppm
did not affect expression levels of MiETR1 in the pedicel and of MiERS1 in the
pericarp; however, MiETR1 in the pericarp at day 2 and MiERS1 in the pedicel at
days 2 and 3 were significantly upregulated over the controls. Moreover, two
novel short versions of the MiERS1 were identified and detected more often in the
pedicel of treated than untreated fruitlets at all sampling times. Sucrose
concentration in the fruitlet pericarp was significantly reduced to the control
at 2 days after both ethephon treatments. In conclusion, it is postulated that
the ethephon-induced abscission process commences with a reduction of the polar
auxin transport capacity in the pedicel, followed by an upregulation of ethylene
receptors and finally a decrease of the sucrose concentration in the fruitlets.
PMID- 26442022
TI - A meta-analysis approach for assessing the diversity and specificity of
belowground root and microbial volatiles.
AB - Volatile organic compounds are secondary metabolites emitted by all organisms,
especially by plants and microbes. Their role as aboveground signals has been
established for decades. Recent evidence suggests that they might have a non
negligible role belowground and might be involved in root-root and root
microbial/pest interactions. Our aim here was to make a comprehensive review of
belowground volatile diversity using a meta-analysis approach. At first we
synthesized current literature knowledge on plant root volatiles and classified
them in terms of chemical diversity. In a second step, relying on the mVOC
database of microbial volatiles, we classified volatiles based on their emitters
(bacteria vs. fungi) and their specific ecological niche (i.e., rhizosphere,
soil). Our results highlight similarities and differences among root and
microbial volatiles and also suggest that some might be niche specific. We
further explored the possibility that volatiles might be involved in intra- and
inter-specific root-root communication and discuss the ecological implications of
such scenario. Overall this work synthesizes current knowledge on the belowground
volatilome and the potential signaling role of its constituents. It also
highlights that the total diversity of belowground volatiles might be orders of
magnitude larger that the few hundreds of compounds described to date.
PMID- 26442023
TI - Signaling in the phytomicrobiome: breadth and potential.
AB - Higher plants have evolved intimate, complex, subtle, and relatively constant
relationships with a suite of microbes, the phytomicrobiome. Over the last few
decades we have learned that plants and microbes can use molecular signals to
communicate. This is well-established for the legume-rhizobia nitrogen-fixing
symbiosis, and reasonably elucidated for mycorrhizal associations. Bacteria
within the phytomircobiome communicate among themselves through quorum sensing
and other mechanisms. Plants also detect materials produced by potential
pathogens and activate pathogen-response systems. This intercommunication
dictates aspects of plant development, architecture, and productivity.
Understanding this signaling via biochemical, genomics, proteomics, and
metabolomic studies has added valuable knowledge regarding development of
effective, low-cost, eco-friendly crop inputs that reduce fossil fuel intense
inputs. This knowledge underpins phytomicrobiome engineering: manipulating the
beneficial consortia that manufacture signals/products that improve the ability
of the plant-phytomicrobiome community to deal with various soil and climatic
conditions, leading to enhanced overall crop plant productivity.
PMID- 26442024
TI - Using targeted enrichment of nuclear genes to increase phylogenetic resolution in
the neotropical rain forest genus Inga (Leguminosae: Mimosoideae).
AB - Evolutionary radiations are prominent and pervasive across many plant lineages in
diverse geographical and ecological settings; in neotropical rainforests there is
growing evidence suggesting that a significant fraction of species richness is
the result of recent radiations. Understanding the evolutionary trajectories and
mechanisms underlying these radiations demands much greater phylogenetic
resolution than is currently available for these groups. The neotropical tree
genus Inga (Leguminosae) is a good example, with ~300 extant species and a crown
age of 2-10 MY, yet over 6 kb of plastid and nuclear DNA sequence data gives only
poor phylogenetic resolution among species. Here we explore the use of larger
scale nuclear gene data obtained though targeted enrichment to increase
phylogenetic resolution within Inga. Transcriptome data from three Inga species
were used to select 264 nuclear loci for targeted enrichment and sequencing.
Following quality control to remove probable paralogs from these sequence data,
the final dataset comprised 259,313 bases from 194 loci for 24 accessions
representing 22 Inga species and an outgroup (Zygia). Bayesian phylogenies
reconstructed using either all loci concatenated or a gene-tree/species-tree
approach yielded highly resolved phylogenies. We used coalescent approaches to
show that the same targeted enrichment data also have significant power to
discriminate among alternative within-species population histories within the
widespread species I. umbellifera. In either application, targeted enrichment
simplifies the informatics challenge of identifying orthologous loci associated
with de novo genome sequencing. We conclude that targeted enrichment provides the
large volumes of phylogenetically-informative sequence data required to resolve
relationships within recent plant species radiations, both at the species level
and for within-species phylogeographic studies.
PMID- 26442025
TI - Tissue specific and abiotic stress regulated transcription of histidine kinases
in plants is also influenced by diurnal rhythm.
AB - Two-component system (TCS) is one of the key signal sensing machinery which
enables species to sense environmental stimuli. It essentially comprises of three
major components, sensory histidine kinase proteins (HKs), histidine
phosphotransfer proteins (Hpts), and response regulator proteins (RRs). The
members of the TCS family have already been identified in Arabidopsis and rice
but the knowledge about their functional indulgence during various abiotic stress
conditions remains meager. Current study is an attempt to carry out comprehensive
analysis of the expression of TCS members in response to various abiotic stress
conditions and in various plant tissues in Arabidopsis and rice using MPSS and
publicly available microarray data. The analysis suggests that despite having
almost similar number of genes, rice expresses higher number of TCS members
during various abiotic stress conditions than Arabidopsis. We found that the TCS
machinery is regulated by not only various abiotic stresses, but also by the
tissue specificity. Analysis of expression of some representative members of TCS
gene family showed their regulation by the diurnal cycle in rice seedlings, thus
bringing-in another level of their transcriptional control. Thus, we report a
highly complex and tight regulatory network of TCS members, as influenced by the
tissue, abiotic stress signal, and diurnal rhythm. The insights on the
comparative expression analysis presented in this study may provide crucial leads
toward dissection of diverse role(s) of the various TCS family members in
Arabidopsis and rice.
PMID- 26442026
TI - Understanding salinity responses and adopting 'omics-based' approaches to
generate salinity tolerant cultivars of rice.
AB - Soil salinity is one of the main constraints affecting production of rice
worldwide, by reducing growth, pollen viability as well as yield of the plant.
Therefore, detailed understanding of the response of rice towards soil salinity
at the physiological and molecular level is a prerequisite for its effective
management. Various approaches have been adopted by molecular biologists or
breeders to understand the mechanism for salinity tolerance in plants and to
develop salt tolerant rice cultivars. Genome wide analysis using 'omics-based'
tools followed by identification and functional validation of individual genes is
becoming one of the popular approaches to tackle this task. On the other hand,
mutation breeding and insertional mutagenesis has also been exploited to obtain
salinity tolerant crop plants. This review looks into various responses at
cellular and whole plant level generated in rice plants toward salinity stress
thus, evaluating the suitability of intervention of functional genomics to raise
stress tolerant plants. We have tried to highlight the usefulness of the
contemporary 'omics-based' approaches such as genomics, proteomics,
transcriptomics and phenomics towards dissecting out the salinity tolerance trait
in rice. In addition, we have highlighted the importance of integration of
various 'omics' approaches to develop an understanding of the machinery involved
in salinity response in rice and to move forward to develop salt tolerant
cultivars of rice.
PMID- 26442027
TI - Differentially expressed seed aging responsive heat shock protein OsHSP18.2
implicates in seed vigor, longevity and improves germination and seedling
establishment under abiotic stress.
AB - Small heat shock proteins (sHSPs) are a diverse group of proteins and are highly
abundant in plant species. Although majority of these sHSPs were shown to express
specifically in seed, their potential function in seed physiology remains to be
fully explored. Our proteomic analysis revealed that OsHSP18.2, a class II
cytosolic HSP is an aging responsive protein as its abundance significantly
increased after artificial aging in rice seeds. OsHSP18.2 transcript was found to
markedly increase at the late maturation stage being highly abundant in dry seeds
and sharply decreased after germination. Our biochemical study clearly
demonstrated that OsHSP18.2 forms homooligomeric complex and is dodecameric in
nature and functions as a molecular chaperone. OsHSP18.2 displayed chaperone
activity as it was effective in preventing thermal inactivation of Citrate
Synthase. Further, to analyze the function of this protein in seed physiology,
seed specific Arabidopsis overexpression lines for OsHSP18.2 were generated. Our
subsequent functional analysis clearly demonstrated that OsHSP18.2 has ability to
improve seed vigor and longevity by reducing deleterious ROS accumulation in
seeds. In addition, transformed Arabidopsis seeds also displayed better
performance in germination and cotyledon emergence under adverse conditions.
Collectively, our work demonstrates that OsHSP18.2 is an aging responsive protein
which functions as a molecular chaperone and possibly protect and stabilize the
cellular proteins from irreversible damage particularly during maturation drying,
desiccation and aging in seeds by restricting ROS accumulation and thereby
improves seed vigor, longevity and seedling establishment.
PMID- 26442028
TI - Comparative analysis of endogenous hormones level in two soybean (Glycine max L.)
lines differing in waterlogging tolerance.
AB - Waterlogged condition due to flooding is one of the major abiotic stresses that
drastically affect the soybean growth and yield around the world. As a result,
many breeders have focused on the development of waterlogging tolerance in
soybean varieties, and thus, several tolerant varieties were developed. However,
the physiological mechanism of waterlogging tolerance is not yet fully
understood. We particularly studied the endogenous hormones regulation during
waterlogging in two contrasting soybean genotypes. According to our results,
adventitious roots were better developed in the waterlogging tolerant line (WTL)
than in the waterlogging susceptible line (WSL). Endogenous hormones also showed
significant differences between WTL and WSL. The ethylene production ratio was
higher in WTL than in WSL, and methionine was higher in WTL than in WSL. Other
endogenous abscisic acid (ABA) contents were lower in WTL than in WSL.
Conversely, gibberellic acid (GA) showed a tendency to be high in WTL, especially
the levels of the bioactive GA4. The ratio of total GA and ABA was significantly
higher in WTL than in WSL. Anatomical study of the root revealed that aerenchyma
cells in the stele were better developed in WTL than in WSL.
PMID- 26442029
TI - A complex protein derivative acts as biogenic elicitor of grapevine resistance
against powdery mildew under field conditions.
AB - Powdery mildew caused by Erysiphe necator is one of the most important grapevine
diseases in several viticulture areas, and high fungicide input is required to
control it. However, numerous synthetic chemical pesticides are under scrutiny
due to concerns about their impact on human health and the environment.
Biopesticides, such as biogenic elicitors, are a promising alternative to
chemical fungicides. Although several studies have reported on effective
elicitors against grapevine diseases, their efficacy under field conditions has
not been investigated extensively or has occurred at rather limited levels. Our
goal was to examine the efficacy of a protein-based composition, namely nutrient
broth (NB), against powdery mildew under field conditions and to characterize its
mechanism of action. Weekly treatments with NB was highly effective in
controlling powdery mildew on grapevine across seasons with different disease
pressures. The level of disease control achieved with NB was comparable to
standard fungicide treatments both on leaves and bunches across three different
years. NB has no direct toxic effect on the germination of E. necator conidia,
and it activates plant resistance with both systemic and translaminar effect in
experiments with artificial inoculation under controlled conditions. NB induced
the expression of defense-related genes in grapevine, demonstrating stimulation
of plant defense mechanisms, prior to and in the early stages of pathogen
infection. NB is a natural derivative from meat and yeast, substances that tend
not to raise concerns about toxicological and ecotoxicological properties. NB
represents a valid control tool for integrated plant protection programs against
powdery mildew, to reduce the use of synthetic pesticides on grapevine.
PMID- 26442031
TI - Co-silencing of tomato S-adenosylhomocysteine hydrolase genes confers increased
immunity against Pseudomonas syringae pv. tomato DC3000 and enhanced tolerance to
drought stress.
AB - S-adenosylhomocysteine hydrolase (SAHH), catalyzing the reversible hydrolysis of
S-adenosylhomocysteine (SAH) to adenosine and homocysteine, is a key enzyme that
maintain the cellular methylation potential in all organisms. We report here the
biological functions of tomato SlSAHHs in stress response. The tomato genome
contains three SlSAHH genes that encode SlSAHH proteins with high level of
sequence identity. qRT-PCR analysis revealed that SlSAHHs responded with distinct
expression induction patterns to Pseudomonas syringae pv. tomato (Pst) DC3000 and
Botrytis cinerea as well as to defense signaling hormones such as salicylic acid,
jasmonic acid and a precursor of ethylene. Virus-induced gene silencing-based
knockdown of individual SlSAHH gene did not affect the growth performance and the
response to Pst DC3000. However, co-silencing of three SlSAHH genes using a
conserved sequence led to significant inhibition of vegetable growth. The SlSAHH
co-silenced plants displayed increased resistance to Pst DC3000 but did not alter
the resistance to B. cinerea. Co-silencing of SlSAHHs resulted in constitutively
activated defense responses including elevated SA level, upregulated expression
of defense-related and PAMP-triggered immunity marker genes and increased callose
deposition and H2O2 accumulation. Furthermore, the SlSAHH-co-silenced plants also
exhibited enhanced drought stress tolerance although they had relatively small
roots. These data demonstrate that, in addition to the functions in growth and
development, SAHHs also play important roles in regulating biotic and abiotic
stress responses in plants.
PMID- 26442030
TI - Local and systemic signaling of iron status and its interactions with homeostasis
of other essential elements.
AB - Iron (Fe) is essential for plant growth and development. However, alkaline soils,
which occupy approximately 30% of the world's arable lands, are considered Fe
limiting for plant growth because insoluble Fe (III) chelates prevail under these
conditions. In contrast, high bioavailability of Fe in acidic soils can be toxic
to plants due to the ability of Fe ions to promote oxidative stress. Therefore,
plants have evolved sophisticated mechanisms to sense and respond to the
fluctuation of Fe availability in the immediate environment and to the needs of
developing shoot tissues to preclude deficiency while avoiding toxicity. In this
review, we focus on recent advances in our understanding of local and systemic
signaling of Fe status with emphasis on the contribution of Fe, its interaction
with other metals and metal ligands in triggering molecular responses that
regulate Fe uptake and partitioning in the plant body.
PMID- 26442032
TI - A novel workflow correlating RNA-seq data to Phythophthora infestans resistance
levels in wild Solanum species and potato clones.
AB - Comparative transcriptomics between species can provide valuable understanding of
plant-pathogen interactions. Here, we focus on wild Solanum species and potato
clones with varying degree of resistance against Phytophthora infestans, which
causes the devastating late blight disease in potato. The transcriptomes of three
wild Solanum species native to Southern Sweden, Solanum dulcamara, Solanum
nigrum, and Solanum physalifolium were compared to three potato clones, Desiree
(cv.), SW93-1015 and Sarpo Mira. Desiree and S. physalifolium are susceptible to
P. infestans whereas the other four have different degrees of resistance. By
building transcript families based on de novo assembled RNA-seq across species
and clones and correlating these to resistance phenotypes, we created a novel
workflow to identify families with expanded or depleted number of transcripts in
relation to the P. infestans resistance level. Analysis was facilitated by
inferring functional annotations based on the family structure and semantic
clustering. More transcript families were expanded in the resistant clones and
species and the enriched functions of these were associated to expected gene
ontology (GO) terms for resistance mechanisms such as hypersensitive response,
host programmed cell death and endopeptidase activity. However, a number of
unexpected functions and transcripts were also identified, for example
transmembrane transport and protein acylation expanded in the susceptible group
and a cluster of Zinc knuckle family proteins expanded in the resistant group.
Over 400 expressed putative resistance (R-)genes were identified and resistant
clones Sarpo Mira and SW93-1015 had ca 25% more expressed putative R-genes than
susceptible cultivar Desiree. However, no differences in numbers of
susceptibility (S-)gene homologs were seen between species and clones. In
addition, we identified P. infestans transcripts including effectors in the early
stages of P. infestans-Solanum interactions.
PMID- 26442033
TI - A Populus TIR1 gene family survey reveals differential expression patterns and
responses to 1-naphthaleneacetic acid and stress treatments.
AB - The plant hormone auxin is a central regulator of plant growth. TRANSPORT
INHIBITOR RESPONSE 1/AUXIN SIGNALING F-BOX (TIR1/AFB) is a component of the E3
ubiquitin ligase complex SCF(TIR1/AFB) and acts as an auxin co-receptor for
nuclear auxin signaling. The SCF(TIR1/AFB)-proteasome machinery plays a central
regulatory role in development-related gene transcription. Populus trichocarpa,
as a model tree, has a unique fast-growth trait to which auxin signaling may
contribute. However, no systematic analyses of the genome organization, gene
structure, and expression of TIR1-like genes have been undertaken in this woody
model plant. In this study, we identified a total of eight TIR1 genes in the
Populus genome that are phylogenetically clustered into four subgroups,
PtrFBL1/PtrFBL2, PtrFBL3/PtrFBL4, PtrFBL5/PtrFBL6, and PtrFBL7/PtrFBL8,
representing four paralogous pairs. In addition, the gene structure and motif
composition were relatively conserved in each paralogous pair and all of the
PtrFBL members were localized in the nucleus. Different sets of PtrFBLs were
strongly expressed in the leaves, stems, roots, cambial zones, and immature xylem
of Populus. Interestingly, PtrFBL1 and 7 were expressed mainly in vascular and
cambial tissues, respectively, indicating their potential but different roles in
wood formation. Furthermore, Populus FBLs responded differentially upon exposure
to various stresses. Finally, over-expression studies indicated a role of FBL1 in
poplar stem growth and response to drought stress. Collectively, these
observations lay the foundation for further investigations into the potential
roles of PtrFBL genes in tree growth and development.
PMID- 26442034
TI - Genetic variation of temperature-regulated curd induction in cauliflower:
elucidation of floral transition by genome-wide association mapping and gene
expression analysis.
AB - Cauliflower (Brassica oleracea var. botrytis) is a vernalization-responsive crop.
High ambient temperatures delay harvest time. The elucidation of the genetic
regulation of floral transition is highly interesting for a precise harvest
scheduling and to ensure stable market supply. This study aims at genetic
dissection of temperature-dependent curd induction in cauliflower by genome-wide
association studies and gene expression analysis. To assess temperature-dependent
curd induction, two greenhouse trials under distinct temperature regimes were
conducted on a diversity panel consisting of 111 cauliflower commercial parent
lines, genotyped with 14,385 SNPs. Broad phenotypic variation and high
heritability (0.93) were observed for temperature-related curd induction within
the cauliflower population. GWA mapping identified a total of 18 QTL localized on
chromosomes O1, O2, O3, O4, O6, O8, and O9 for curding time under two distinct
temperature regimes. Among those, several QTL are localized within regions of
promising candidate flowering genes. Inferring population structure and genetic
relatedness among the diversity set assigned three main genetic clusters. Linkage
disequilibrium (LD) patterns estimated global LD extent of r(2) = 0.06 and a
maximum physical distance of 400 kb for genetic linkage. Transcriptional
profiling of flowering genes FLOWERING LOCUS C (BoFLC) and VERNALIZATION 2
(BoVRN2) was performed, showing increased expression levels of BoVRN2 in
genotypes with faster curding. However, functional relevance of BoVRN2 and BoFLC2
could not consistently be supported, which probably suggests to act facultative
and/or might evidence for BoVRN2/BoFLC-independent mechanisms in temperature
regulated floral transition in cauliflower. Genetic insights in temperature
regulated curd induction can underpin genetically informed phenology models and
benefit molecular breeding strategies toward the development of thermo-tolerant
cultivars.
PMID- 26442035
TI - Structural and metabolic changes in rhizophores of the Cerrado species
Chrysolaena obovata (Less.) Dematt. as influenced by drought and re-watering.
AB - The high fructan contents in underground organs of Cerrado species, high water
solubility, and fast metabolism of these compounds highlight their role as carbon
storage and as an adaptive feature in plants under drought. In this study, we
showed that anatomical structure, in association with soluble compounds and
metabolism of inulin-type fructans were modified in rhizophores of Crysolaena
obovata submitted to water suppression and recovery after re-watering. Plants
were subjected to daily watering (control), suppression of watering for 22 days
(water suppression) and suppression of watering followed by re-watering after 10
days (re-watered). Plants were collected at time 0 and after 3, 7, 10, 12, 17,
and 22 days of treatment. In addition to changes in fructan metabolism, high
proline content was detected in drought stressed plants, contributing to
osmoregulation and recovery after water status reestablishment. Under water
suppression, total inulin was reduced from approx. 60 to 40%, mainly due to
exohydrolase activity. Concurrently, the activity of fructosyltransferases
promoted the production of short chain inulin, which could contribute to the
increase in osmotic potential. After re-watering, most parameters analyzed were
similar to those of control plants, indicating the resumption of regular
metabolism, after water absorption. Inulin sphero-crystals accumulated in
parenchymatic cells of the cortex, vascular tissues and pith were reduced under
drought and accompanied anatomical changes, starting from day 10. At 22 days of
drought, the cortical and vascular tissues were collapsed, and inulin sphero
crystals and inulin content were reduced. The localization of inulin sphero
crystals in vascular tissues of C. obovata, as well as the decrease of total
inulin and the increase in oligo:polysaccharide ratio in water stressed plants is
consistent with the role of fructans in protecting plants against drought.
PMID- 26442036
TI - Inter-organismal signaling and management of the phytomicrobiome.
AB - The organisms of the phytomicrobiome use signal compounds to regulate aspects of
each other's behavior. Legumes use signals (flavonoids) to regulate rhizobial nod
gene expression during establishment of the legume-rhizobia N2-fixation
symbiosis. Lipochitooligosaccharides (LCOs) produced by rhizobia act as return
signals to the host plant and are recognized by specific lysine motif receptor
like kinases, which triggers a signal cascade leading to nodulation of legume
roots. LCOs also enhance plant growth, particularly when plants are stressed.
Chitooligosaccharides activate plant immune responses, providing enhanced
resistance against diseases. Co-inoculation of rhizobia with other plant growth
promoting rhizobacteria (PGPR) can improve nodulation and crop growth. PGPR also
alleviate plant stress by secreting signal compounds including phytohormones and
antibiotics. Thuricin 17, a small bacteriocin produced by a phytomicrobiome
member promotes plant growth. Lumichrome synthesized by soil rhizobacteria
function as stress-sensing cues. Inter-organismal signaling can be used to
manage/engineer the phytomicrobiome to enhance crop productivity, particularly in
the face of stress. Stressful conditions are likely to become more frequent and
more severe because of climate change.
PMID- 26442037
TI - Shared and unique responses of plants to multiple individual stresses and stress
combinations: physiological and molecular mechanisms.
AB - In field conditions, plants are often simultaneously exposed to multiple biotic
and abiotic stresses resulting in substantial yield loss. Plants have evolved
various physiological and molecular adaptations to protect themselves under
stress combinations. Emerging evidences suggest that plant responses to a
combination of stresses are unique from individual stress responses. In addition,
plants exhibit shared responses which are common to individual stresses and
stress combination. In this review, we provide an update on the current
understanding of both unique and shared responses. Specific focus of this review
is on heat-drought stress as a major abiotic stress combination and, drought
pathogen and heat-pathogen as examples of abiotic-biotic stress combinations. We
also comprehend the current understanding of molecular mechanisms of cross talk
in relation to shared and unique molecular responses for plant survival under
stress combinations. Thus, the knowledge of shared responses of plants from
individual stress studies and stress combinations can be utilized to develop
varieties with broad spectrum stress tolerance.
PMID- 26442038
TI - Quantifying floral shape variation in 3D using microcomputed tomography: a case
study of a hybrid line between actinomorphic and zygomorphic flowers.
AB - The quantification of floral shape variations is difficult because flower
structures are both diverse and complex. Traditionally, floral shape variations
are quantified using the qualitative and linear measurements of two-dimensional
(2D) images. The 2D images cannot adequately describe flower structures, and thus
lead to unsatisfactory discrimination of the flower shape. This study aimed to
acquire three-dimensional (3D) images by using microcomputed tomography (MUCT)
and to examine the floral shape variations by using geometric morphometrics (GM).
To demonstrate the advantages of the 3D-MUCT-GM approach, we applied the approach
to a second-generation population of florist's gloxinia (Sinningia speciosa)
crossed from parents of zygomorphic and actinomorphic flowers. The flowers in the
population considerably vary in size and shape, thereby served as good materials
to test the applicability of the proposed phenotyping approach. Procedures were
developed to acquire 3D volumetric flower images using a MUCT scanner, to segment
the flower regions from the background, and to select homologous characteristic
points (i.e., landmarks) from the flower images for the subsequent GM analysis.
The procedures identified 95 landmarks for each flower and thus improved the
capability of describing and illustrating the flower shapes, compared with
typically lower number of landmarks in 2D analyses. The GM analysis demonstrated
that flower opening and dorsoventral symmetry were the principal shape variations
of the flowers. The degrees of flower opening and corolla asymmetry were then
subsequently quantified directly from the 3D flower images. The 3D-MUCT-GM
approach revealed shape variations that could not be identified using typical 2D
approaches and accurately quantified the flower traits that presented a challenge
in 2D images. The approach opens new avenues to investigate floral shape
variations.
PMID- 26442039
TI - Metabolic engineering of the chloroplast genome reveals that the yeast ArDH gene
confers enhanced tolerance to salinity and drought in plants.
AB - Osmoprotectants stabilize proteins and membranes against the denaturing effect of
high concentrations of salts and other harmful solutes. In yeast, arabitol
dehydrogenase (ArDH) reduces D-ribulose to D-arabitol where D-ribulose is derived
by dephosphorylating D-ribulose-5-PO4 in the oxidized pentose pathway.
Osmotolerance in plants could be developed through metabolic engineering of
chloroplast genome by introducing genes encoding polyols since chloroplasts offer
high level transgene expression and containment. Here, we report that ArDH
expression in tobacco chloroplasts confers tolerance to NaCl (up to 400 mM).
Transgenic plants compared to wild type (WT) survived for only 4-5 weeks on 400
mM NaCl whereas plants remained green and grew normal on concentrations up to 350
mM NaCl. Further, a-week-old seedlings were also challenged with poly ethylene
glycol (PEG, up to 6%) in the liquid medium, considering that membranes and
proteins are protected under stress conditions due to accumulation of arabitol in
chloroplasts. Seedlings were tolerant to 6% PEG, suggesting that ARDH enzyme
maintains integrity of membranes in chloroplasts under drought conditions via
metabolic engineering. Hence, the gene could be expressed in agronomic plants to
withstand abiotic stresses.
PMID- 26442040
TI - Companion cropping with potato onion enhances the disease resistance of tomato
against Verticillium dahliae.
AB - Intercropping could alleviate soil-borne diseases, however, few studies focused
on the immunity of the host plant induced by the interspecific interactions. To
test whether or not intercropping could enhance the disease resistance of host
plant, we investigated the effect of companion cropping with potato onion on
tomato Verticillium wilt caused by Verticillium dahliae (V. dahliae). To
investigate the mechanisms, the root exudates were collected from tomato and
potato onion which were grown together or separately, and were used to examine
the antifungal activities against V. dahliae in vitro, respectively. Furthermore,
RNA-seq was used to examine the expression pattern of genes related to disease
resistance in tomato companied with potato onion compared to that in tomato grown
alone, under the condition of infection with V. dahliae. The results showed that
companion cropping with potato onion could alleviate the incidence and severity
of tomato Verticillium wilt. The further studies revealed that the root exudates
from tomato companied with potato onion significantly inhibited the mycelia
growth and spore germination of V. dahliae. However, there were no significant
effects on these two measurements for the root exudates from potato onion grown
alone or from potato onion grown with tomato. RNA-seq data analysis showed the
disease defense genes associated with pathogenesis-related proteins, biosynthesis
of lignin, hormone metabolism and signal transduction were expressed much higher
in the tomato companied with potato onion than those in the tomato grown alone,
which indicated that these defense genes play important roles in tomato against
V. dahliae infection, and meant that the disease resistance of tomato against V.
dahliae was enhanced in the companion copping with potato onion. We proposed that
companion cropping with potato onion could enhance the disease resistance of
tomato against V. dahliae by regulating the expression of genes related to
disease resistance response. This may be a potential mechanism for the management
of soil-borne plant diseases in the intercropping system.
PMID- 26442041
TI - Evaluation on the effectiveness of 2-deoxyglucose-6-phosphate phosphatase
(DOG(R)1) gene as a selectable marker for oil palm (Elaeis guineensis Jacq.)
embryogenic calli transformation mediated by Agrobacterium tumefaciens.
AB - DOG(R)1, which encodes 2-deoxyglucose-6-phosphate phosphatase, has been used as a
selectable marker gene to produce transgenic plants. In this study, a
transformation vector, pBIDOG, which contains the DOG(R)1 gene, was transformed
into oil palm embryogenic calli (EC) mediated by Agrobacterium tumefaciens strain
LBA4404. Transformed EC were exposed to 400 mg l(-1) 2-deoxyglucose (2-DOG) as
the selection agent. 2-DOG resistant tissues were regenerated into whole
plantlets on various regeneration media containing the same concentration of 2
DOG. The plantlets were later transferred into soil and grown in a biosafety
screenhouse. PCR and subsequently Southern blot analyses were carried out to
confirm the integration of the transgene in the plantlets. A transformation
efficiency of about 1.0% was obtained using DOG(R)1 gene into the genome of oil
palm. This result demonstrates the potential of using combination of DOG(R)1 gene
and 2-DOG for regenerating transgenic oil palm.
PMID- 26442043
TI - The plant detectives: innovative undergraduate teaching to inspire the next
generation of plant biologists.
AB - Encouraging more students to embrace plant science research is a global priority.
We have evolved a second year undergraduate course from a standard
lecture/practical format into an innovative research-led learning design that
gives students hands-on experience of cutting-edge plant science research and
specialist instrumentation. By making tangible the links between plant genetics,
biochemistry, physiology and function, the active learning curriculum extends
students to their limits, and gives them insights into the multi-faceted nature
of plant science research. Using genetically-mapped mutants of Arabidopsis
thaliana, we challenge our students to apply their conceptual learning
immediately to identify "unknown" genetic mutations affecting plant form and
function. By exposing students early in their student careers to the challenges,
rigors and excitement of plant science research, we have helped them grow quickly
into astute researchers who truly deserve the title "Plant Detectives." Many have
become motivated to continue their studies as plant biologists in research
focused honors (pre-doctoral) and doctoral programs.
PMID- 26442042
TI - Metabolite profiling and transcript analysis reveal specificities in the response
of a berry derived cell culture to abiotic stresses.
AB - As climate changes, there is a need to understand the expected effects on
viticulture. In nature, stresses exist in a combined manner, hampering the
elucidation of the effect of individual cues on grape berry metabolism. Cell
suspension culture originated from pea-size Gamy Red grape berry was used to
harness metabolic response to high light (HL; 2500 MUmol m(-2)s(-1)), high
temperature (HT; 40 degrees C) and their combination in comparison to 25 degrees
C and 100 MUmol m(-2)s(-1) under controlled condition. When LC-MS and GC-MS based
metabolite profiling was implemented and integrated with targeted RT-qPCR
transcript analysis specific responses were observed to the different cues. HL
enhanced polyphenol metabolism while HT and its combination with HL induced amino
acid and organic acid metabolism with additional effect on polyphenols. The trend
of increment in TCA cycle genes like ATCs, ACo1, and IDH in the combined
treatment might support the observed increment in organic acids, GABA shunt, and
their derivatives. The apparent phenylalanine reduction with polyphenol increment
under HL suggests enhanced fueling of the precursor toward the downstream
phenylpropanoid pathway. In the polyphenol metabolism, a differential pattern of
expression of flavonoid 3',5' hydroxylase and flavonoid 3' hydroxylase was
observed under high light (HL) and combined cues which were accompanied by
characteristic metabolite profiles. HT decreased glycosylated cyanidin and
peonidin forms while the combined cues increased acetylated and coumarylated
peonidin forms. Transcription factors regulating anthocyanin metabolism and their
methylation, MYB, OMT, UFGT, and DFR, were expressed differentially among the
treatments, overall in agreement with the metabolite profiles. Taken together
these data provide insights into the coordination of central and secondary
metabolism in relation to multiple abiotic stresses.
PMID- 26442044
TI - Plasticity in variation of xylem and phloem cell characteristics of Norway spruce
under different local conditions.
AB - There is limited information on intra-annual plasticity of secondary tissues of
tree species growing under different environmental conditions. To increase the
knowledge about the plasticity of secondary growth, which allows trees to adapt
to specific local climatic regimes, we examined climate-radial growth
relationships of Norway spruce [Picea abies (L.) H. Karst.] from three
contrasting locations in the temperate climatic zone by analyzing tree-ring
widths for the period 1932-2010, and cell characteristics in xylem and phloem
increments formed in the years 2009-2011. Variation in the structure of xylem and
phloem increments clearly shows that plasticity in seasonal dynamics of cambial
cell production and cell differentiation exists on xylem and phloem sides.
Anatomical characteristics of xylem and phloem cells are predominantly site
specific characteristics, because they varied among sites but were fairly uniform
among years in trees from the same site. Xylem and phloem tissues formed in the
first part of the growing season seemed to be more stable in structure,
indicating their priority over latewood and late phloem for tree performance.
Long-term climate and radial growth analyses revealed that growth was in general
less dependent on precipitation than on temperature; however, growth sensitivity
to local conditions differed among the sites. Only partial dependence of radial
growth of spruce on climatic factors on the selected sites confirms its strategy
to adapt the structure of wood and phloem increments to function optimally in
local conditions.
PMID- 26442045
TI - Identification of early salt stress responsive proteins in seedling roots of
upland cotton (Gossypium hirsutum L.) employing iTRAQ-based proteomic technique.
AB - Soil salinity is a major abiotic stress that limits plant growth and agricultural
productivity. Upland cotton (Gossypium hirsutum L.) is highly tolerant to
salinity; however, large-scale proteomic data of cotton in response to salt
stress are still scant. Here, an isobaric tag for relative and absolute
quantitation (iTRAQ)-based proteomic technique was employed to identify the early
differentially expressed proteins (DEPs) from salt-treated cotton roots. One
hundred and twenty-eight DEPs were identified, 76 of which displayed increased
abundance and 52 decreased under salt stress conditions. The majority of the
proteins have functions related to carbohydrate and energy metabolism,
transcription, protein metabolism, cell wall and cytoskeleton metabolism,
membrane and transport, signal transduction, in addition to stress and defense.
It is worth emphasizing that some novel salt-responsive proteins were identified,
which are involved in cell cytoskeleton metabolism (actin-related protein2, ARP2,
and fasciclin-like arabinogalactan proteins, FLAs), membrane transport (tonoplast
intrinsic proteins, TIPs, and plasma membrane intrinsic proteins, PIPs), signal
transduction (leucine-rich repeat receptor-like kinase encoding genes, LRR-RLKs)
and stress responses (thaumatin-like protein, TLP, universal stress protein, USP,
dirigent-like protein, DIR, desiccation-related protein PCC13-62). High positive
correlation between the abundance of some altered proteins (superoxide dismutase,
SOD, peroxidase, POD, glutathione S-transferase, GST, monodehydroascorbate
reductase, MDAR, and malate dehydrogenase, MDH) and their enzyme activity was
evaluated. The results demonstrate that the iTRAQ-based proteomic technique is
reliable for identifying and quantifying a large number of cotton root proteins.
qRT-PCR was used to study the gene expression levels of the five above-mentioned
proteins; four patterns are consistent with those of induced protein. These
results showed that the proteome of cotton roots under NaCl stress is complex.
The comparative protein profiles of roots under salinity vs control improves the
understanding of the molecular mechanisms involved in the tolerance of plants to
salt stress. This work provides a good basis for further functional elucidation
of these DEPs using genetic and/or other approaches, and, consequently, candidate
genes for genetic engineering to improve crop salt tolerance.
PMID- 26442046
TI - Potential of soil amendments (Biochar and Gypsum) in increasing water use
efficiency of Abelmoschus esculentus L. Moench.
AB - Water being an essential component for plant growth and development, its scarcity
poses serious threat to crops around the world. Climate changes and global
warming are increasing the temperature of earth hence becoming an ultimate cause
of water scarcity. It is need of the day to use potential soil amendments that
could increase the plants' resistance under such situations. Biochar and gypsum
were used in the present study to improve the water use efficiency (WUE) and
growth of Abelmoschus esculentus L. Moench (Lady's Finger). A 6 weeks experiment
was conducted under greenhouse conditions. Stress treatments were applied after
30 days of sowing. Plant height, leaf area, photosynthesis, transpiration rate
(Tr), stomatal conductance and WUE were determined weekly under stressed [60%
field capacity (F.C.)] and non-stressed (100% F.C.) conditions. Stomatal
conductance and Tr decreased and reached near to zero in stressed plants.
Stressed plants also showed resistance to water stress upto 5 weeks and gradually
perished at sixth week. On the other hand, WUE improved in stressed plants
containing biochar and gypsum as compared to untreated plants. Biochar alone is a
better strategy to promote plant growth and WUE specifically of A. esculentus,
compared to its application in combination with gypsum.
PMID- 26442047
TI - A stranger in a strange land: the utility and interpretation of heterologous
expression.
AB - One of the major goals of the modern study of evodevo is to understand the
evolution of gene function across a range of contexts, including
sub/neofunctionalization, co-option of genetic modules, and the evolution of
morphological novelty. To these ends, comparative studies of gene expression can
be useful for constructing hypotheses, but cannot provide direct evidence of
functional evolution. Unfortunately, determining endogenous gene function in non
model species is often not an option. Faced with this dilemma, a common approach
is to use heterologous expression (HE) in genetically tractable model species as
a proxy for functional analyses. Such experiments have important limitations,
however, and require caution in the interpretation of their results. How do we
dissociate biochemical function from its original genomic context? In the end,
what does HE actually tell us? Here, I argue that HE only sheds light on specific
types of biochemical conservation, but can be useful when experiments are
carefully interpreted.
PMID- 26442048
TI - Proteomic analysis of middle and late stages of bread wheat (Triticum aestivum
L.) grain development.
AB - Proteomic approaches were applied in four grain developmental stages of the
Chinese bread wheat Yunong 201 and its ethyl methanesulfonate (EMS) mutant line
Yunong 3114. 2-DE and tandem MALDI-TOF/TOF-MS analyzed proteome characteristics
during middle and late grain development of the Chinese bread wheat Yunong 201
and its EMS mutant line Yunong 3114 with larger grain sizes. We identified 130
differentially accumulated protein spots representing 88 unique proteins, and
four main expression patterns displayed a dynamic description of middle and late
grain formation. Those identified protein species participated in eight
biochemical processes: stress/defense, carbohydrate metabolism, protein
synthesis/assembly/degradation, storage proteins, energy production and
transportation, photosynthesis, transcription/translation, signal transduction.
Comparative proteomic characterization demonstrated 12 protein spots that co
accumulated in the two wheat cultivars with different expression patterns, and
six cultivar-specific protein spots including serpin, small heat shock protein,
beta-amylase, alpha-amylase inhibitor, dimeric alpha-amylase inhibitor precursor,
and cold regulated protein. These cultivar-specific protein spots possibly
resulted in differential yield-related traits of the two wheat cultivars. Our
results provide valuable information for dissection of molecular and genetics
basis of yield-related traits in bread wheat and the proteomic characterization
in this study could also provide insights in the biology of middle and late grain
development.
PMID- 26442049
TI - Identification, isolation, and expression analysis of heat shock transcription
factors in the diploid woodland strawberry Fragaria vesca.
AB - Heat shock transcription factors (Hsfs) are known to play dominant roles in plant
responses to heat, as well as other abiotic or biotic stress stimuli. While the
strawberry is an economically important fruit plant, little is known about the
Hsf family in the strawberry. To explore the functions of strawberry Hsfs in
abiotic and biotic stress responses, this study identified 17 Hsf genes (FvHsfs)
in a wild diploid woodland strawberry (Fragaria vesca, 2n = 2x = 14) and isolated
14 of these genes. Phylogenetic analysis divided the strawberry FvHsfs genes into
three main groups. The evolutionary and structural analyses revealed that the
FvHsf family is conserved. The promoter sequences of the FvHsf genes contain
upstream regulatory elements corresponding to different stress stimuli. In
addition, 14 FvHsf-GFP fusion proteins showed differential subcellular
localization in Arabidopsis mesophyll protoplasts. Furthermore, we examined the
expression of the 17 FvHsf genes in wild diploid woodland strawberries under
various conditions, including abiotic stresses (heat, cold, drought, and salt),
biotic stress (powdery mildew infection), and hormone treatments (abscisic acid,
ethephon, methyl jasmonate, and salicylic acid). Fifteen of the seventeen FvHsf
genes exhibited distinct changes on the transcriptional level during heat
treatment. Of these 15 FvHsfs, 8 FvHsfs also exhibited distinct responses to
other stimuli on the transcriptional level, indicating versatile roles in the
response to abiotic and biotic stresses. Taken together, the present work may
provide the basis for further studies to dissect FvHsf function in response to
stress stimuli.
PMID- 26442050
TI - Genome-wide identification and expression analysis of calcium-dependent protein
kinase and its closely related kinase genes in Capsicum annuum.
AB - As Ca2+ sensors and effectors, calcium-dependent protein kinases (CDPKs) play
important roles in plant growth, development, and response to environmental cues.
However, no CDPKs have been characterized in Capsicum annuum thus far. Herein, a
genome wide comprehensive analysis of genes encoding CDPKs and CDPK-related
protein kinases (CRKs) was performed in pepper, a total of 31 CDPK genes and five
closely related kinase genes were identified, which were phylogenetically divided
into four distinct subfamilies and unevenly distributed across nine chromosomes.
Conserved sequence and exon-intron structures were found to be shared by pepper
CDPKs within the same subfamily, and the expansion of the CDPK family in pepper
was found to be due to segmental duplication events. Five CDPKs in the C. annuum
variety CM334 were found to be mutated in the Chiltepin variety, and one CDPK
present in CM334 was lost in Chiltepin. The majority of CDPK and CRK genes were
expressed in different pepper tissues and developmental stages, and 10, 12, and 8
CDPK genes were transcriptionally modified by salt, heat, and Ralstonia
solanacearum stresses, respectively. Furthermore, these genes were found to
respond specifically to one stress as well as respond synergistically to two
stresses or three stresses, suggesting that these CDPK genes might be involved in
the specific or synergistic response of pepper to salt, heat, and R.
solanacearum. Our results lay the foundation for future functional
characterization of pepper CDPK and its closely related gene families.
PMID- 26442051
TI - Hierarchical additive effects on heterosis in rice (Oryza sativa L.).
AB - Exploitation of heterosis in crops has contributed greatly to improvement in
global food and energy production. In spite of the pervasive importance of
heterosis, a complete understanding of its mechanisms has remained elusive. In
this study, a small test-crossed rice population was constructed to investigate
the formation mechanism of heterosis for 13 traits. The results of the relative
mid-parent heterosis and modes of inheritance of all investigated traits
demonstrated that additive effects were the foundation of heterosis for complex
traits in a hierarchical structure, and multiplicative interactions among the
component traits were the framework of heterosis in complex traits. Furthermore,
new balances between unit traits and related component traits provided hybrids
with the opportunity to achieve an optimal degree of heterosis for complex
traits. This study dissected heterosis of both reproductive and vegetative traits
from the perspective of hierarchical structure for the first time. Additive
multiplicative interactions of component traits were proven to be the origin of
heterosis in complex traits. Meanwhile, more attention should be paid to
component traits, rather than complex traits, in the process of revealing the
mechanism of heterosis.
PMID- 26442052
TI - Global analysis of lysine acetylation in strawberry leaves.
AB - Protein lysine acetylation is a reversible and dynamic post-translational
modification. It plays an important role in regulating diverse cellular processes
including chromatin dynamic, metabolic pathways, and transcription in both
prokaryotes and eukaryotes. Although studies of lysine acetylome in plants have
been reported, the throughput was not high enough, hindering the deep
understanding of lysine acetylation in plant physiology and pathology. In this
study, taking advantages of anti-acetyllysine-based enrichment and high-sensitive
mass spectrometer, we applied an integrated proteomic approach to comprehensively
investigate lysine acetylome in strawberry. In total, we identified 1392
acetylation sites in 684 proteins, representing the largest dataset of acetylome
in plants to date. To reveal the functional impacts of lysine acetylation in
strawberry, intensive bioinformatic analysis was performed. The results
significantly expanded our current understanding of plant acetylome and
demonstrated that lysine acetylation is involved in multiple cellular metabolism
and cellular processes. More interestingly, nearly 50% of all acetylated proteins
identified in this work were localized in chloroplast and the vital role of
lysine acetylation in photosynthesis was also revealed. Taken together, this
study not only established the most extensive lysine acetylome in plants to date,
but also systematically suggests the significant and unique roles of lysine
acetylation in plants.
PMID- 26442053
TI - Crop improvement using life cycle datasets acquired under field conditions.
AB - Crops are exposed to various environmental stresses in the field throughout their
life cycle. Modern plant science has provided remarkable insights into the
molecular networks of plant stress responses in laboratory conditions, but the
responses of different crops to environmental stresses in the field need to be
elucidated. Recent advances in omics analytical techniques and information
technology have enabled us to integrate data from a spectrum of physiological
metrics of field crops. The interdisciplinary efforts of plant science and data
science enable us to explore factors that affect crop productivity and identify
stress tolerance-related genes and alleles. Here, we describe recent advances in
technologies that are key components for data driven crop design, such as
population genomics, chronological omics analyses, and computer-aided molecular
network prediction. Integration of the outcomes from these technologies will
accelerate our understanding of crop phenology under practical field situations
and identify key characteristics to represent crop stress status. These elements
would help us to genetically engineer "designed crops" to prevent yield
shortfalls because of environmental fluctuations due to future climate change.
PMID- 26442054
TI - Differential expression of seven conserved microRNAs in response to abiotic
stress and their regulatory network in Helianthus annuus.
AB - Biotic and abiotic stresses affect plant development and production through
alternation of the gene expression pattern. Gene expression itself is under the
control of different regulators such as miRNAs and transcription factors (TFs).
MiRNAs are known to play important roles in regulation of stress responses via
interacting with their target mRNAs. Here, for the first time, seven conserved
miRNAs, associated with drought, heat, salt and cadmium stresses were
characterized in sunflower. The expression profiles of miRNAs and their targets
were comparatively analyzed between leaves and roots of plants grown under the
mentioned stress conditions. Gene ontology analysis of target genes revealed that
they are involved in several important pathways such as auxin and ethylene
signaling, RNA mediated silencing and DNA methylation processes. Gene regulatory
network highlighted the existence of cross-talks between these stress-responsive
miRNAs and the other stress responsive genes in sunflower. Based on network
analysis, we suggest that some of these miRNAs in sunflower such as miR172 and
miR403 may play critical roles in epigenetic responses to stress. It seems that
depending on the stress type, theses miRNAs target several pathways and cellular
processes to help sunflower to cope with drought, heat, salt and cadmium stress
conditions in a tissue-associated manner.
PMID- 26442055
TI - The auxin response factor gene family in banana: genome-wide identification and
expression analyses during development, ripening, and abiotic stress.
AB - Auxin signaling regulates various auxin-responsive genes via two types of
transcriptional regulators, Auxin Response Factors (ARF) and Aux/IAA. ARF
transcription factors act as critical components of auxin signaling that play
important roles in modulating various biological processes. However, limited
information about this gene family in fruit crops is currently available. Herein,
47 ARF genes were identified in banana based on its genome sequence. Phylogenetic
analysis of the ARFs from banana, rice, and Arabidopsis suggested that the ARFs
could be divided into four subgroups, among which most ARFs from the banana
showed a closer relationship with those from rice than those from Arabidopsis.
Conserved motif analysis showed that all identified MaARFs had typical DNA
binding and ARF domains, but 12 members lacked the dimerization domain. Gene
structure analysis showed that the number of exons in MaARF genes ranged from 5
to 21, suggesting large variation amongst banana ARF genes. The comprehensive
expression profiles of MaARF genes yielded useful information about their
involvement in diverse tissues, different stages of fruit development and
ripening, and responses to abiotic stresses in different varieties. Interaction
networks and co-expression assays indicated the strong transcriptional response
of banana ARFs and ARF-mediated networks in early fruit development for different
varieties. Our systematic analysis of MaARFs revealed robust tissue-specific,
development-dependent, and abiotic stress-responsive candidate MaARF genes for
further functional assays in planta. These findings could lead to potential
applications in the genetic improvement of banana cultivars, and yield new
insights into the complexity of the control of MaARF gene expression at the
transcriptional level. Finally, they support the hypothesis that ARFs are a
crucial component of the auxin signaling pathway, which regulates a wide range of
physiological processes.
PMID- 26442056
TI - Genome-wide association for grain yield under rainfed conditions in historical
wheat cultivars from Pakistan.
AB - Genome-wide association studies (GWAS) were undertaken to identify SNP markers
associated with yield and yield-related traits in 123 Pakistani historical wheat
cultivars evaluated during 2011-2014 seasons under rainfed field conditions. The
population was genotyped by using high-density Illumina iSelect 90K single
nucleotide polymorphism (SNP) assay, and finally 14,960 high quality SNPs were
used in GWAS. Population structure examined using 1000 unlinked markers
identified seven subpopulations (K = 7) that were representative of different
breeding programs in Pakistan, in addition to local landraces. Forty four stable
marker-trait associations (MTAs) with -log p > 4 were identified for nine yield
related traits. Nine multi-trait MTAs were found on chromosomes 1AL, 1BS, 2AL,
2BS, 2BL, 4BL, 5BL, 6AL, and 6BL, and those on 5BL and 6AL were stable across two
seasons. Gene annotation and syntey identified that 14 trait-associated SNPs were
linked to genes having significant importance in plant development. Favorable
alleles for days to heading (DH), plant height (PH), thousand grain weight (TGW),
and grain yield (GY) showed minor additive effects and their frequencies were
slightly higher in cultivars released after 2000. However, no selection pressure
on any favorable allele was identified. These genomic regions identified have
historically contributed to achieve yield gains from 2.63 million tons in 1947 to
25.7 million tons in 2015. Future breeding strategies can be devised to initiate
marker assisted breeding to accumulate these favorable alleles of SNPs associated
with yield-related traits to increase grain yield. Additionally, in silico
identification of 454-contigs corresponding to MTAs will facilitate fine mapping
and subsequent cloning of candidate genes and functional marker development.
PMID- 26442057
TI - Temporal small RNA transcriptome profiling unraveled partitioned miRNA expression
in developing maize endosperms between reciprocal crosses.
AB - In angiosperms, the endosperm nurtures the embryo and provides nutrients for seed
germination. To identify the expression pattern of small interfering RNA in the
developing maize endosperm, we have performed high-throughput small RNA
transcriptome sequencing of kernels at 0, 3, and 5 days after pollination (DAP)
and endosperms at 7, 10, and 15 DAP using B73 and Mo17 reciprocal crosses in
previous study. Here, we further explored these small RNA-seq data to investigate
the potential roles of miRNAs in regulating the gene expression process. In
total, 57 conserved miRNAs and 18 novel miRNAs were observed highly expressed in
maize endosperm. Temporal expression profiling indicated that these miRNAs
exhibited dynamic and partitioned expression patterns at different developmental
stages between maize reciprocal crosses, and quantitative RT-PCR results further
confirmed our observation. In addition, we found a subset of distinct tandem
miRNAs are generated from a single stem-loop structure in maize that might be
conserved in monocots. Furthermore, a SNP variation of Zma-miR408-5p at 11th base
position was characterized between B73 and Mo17 which might lead to completely
different functions in repressing targets. More interestingly, Zma-miR408-5p
exhibited B73-biased expression pattern in the B73 and Mo17 reciprocal hybrid
endosperms at 7, 10, and 15 DAP according to the reads abundance with SNPs and
CAPS experiment. Together, this study suggests that miRNA plays a crucial role in
regulating endosperm development, and exhibited distinct expression patterns in
developing endosperm between maize reciprocal crosses.
PMID- 26442058
TI - Analysis of the transgenerational iron deficiency stress memory in Arabidopsis
thaliana plants.
AB - We investigated the existence of the transgenerational memory of iron (Fe)
deficiency stress, in Arabidopsis thaliana. Plants were grown under Fe
deficiency/sufficiency, and so were their offspring. The frequency of somatic
homologous recombination (SHR) events, of DNA strand breaks as well as the
expression of the transcription elongation factor TFIIS-like gene increase when
plants are grown under Fe deficiency. However, SHR frequency, DNA strand break
events, and TFIIS-like gene expression do not increase further when plants are
grown for more than one generation under the same stress, and furthermore, they
decrease back to control values within two succeeding generations grown under
control conditions, regardless of the Fe deficiency stress history of the mother
plants. Seedlings produced from plants grown under Fe deficiency evolve more
oxygen than control seedlings, when grown under Fe sufficiency: however, this
trait is not associated with any change in the protein profile of the
photosynthetic apparatus and is not transmitted to more than one generation.
Lastly, plants grown for multiple generations under Fe deficiency produce seeds
with greater longevity: however, this trait is not inherited in offspring
generations unexposed to stress. These findings suggest the existence of multiple
step control of mechanisms to prevent a genuine and stable transgenerational
transmission of Fe deficiency stress memory, with the tightest control on DNA
integrity.
PMID- 26442059
TI - Expression of Arabidopsis FCS-Like Zinc finger genes is differentially regulated
by sugars, cellular energy level, and abiotic stress.
AB - Cellular energy status is an important regulator of plant growth, development,
and stress mitigation. Environmental stresses ultimately lead to energy deficit
in the cell which activates the SNF1-RELATED KINASE 1 (SnRK1) signaling cascade
which eventually triggering a massive reprogramming of transcription to enable
the plant to survive under low-energy conditions. The role of Arabidopsis
thaliana FCS-Like Zinc finger (FLZ) gene family in energy and stress signaling is
recently come to highlight after their interaction with kinase subunits of SnRK1
were identified. In a detailed expression analysis in different sugars, energy
starvation, and replenishment series, we identified that the expression of most
of the FLZ genes is differentially modulated by cellular energy level. It was
found that FLZ gene family contains genes which are both positively and
negatively regulated by energy deficit as well as energy-rich conditions. Genetic
and pharmacological studies identified the role of HEXOKINASE 1- dependent and
energy signaling pathways in the sugar-induced expression of FLZ genes. Further,
these genes were also found to be highly responsive to different stresses as well
as abscisic acid. In over-expression of kinase subunit of SnRK1, FLZ genes were
found to be differentially regulated in accordance with their response toward
energy fluctuation suggesting that these genes may work downstream to the
established SnRK1 signaling under low-energy stress. Taken together, the present
study provides a conceptual framework for further studies related to SnRK1-FLZ
interaction in relation to sugar and energy signaling and stress response.
PMID- 26442060
TI - Photosynthetic characteristics of the subtending leaf of cotton boll at different
fruiting branch nodes and their relationships with lint yield and fiber quality.
AB - To investigate photosynthetic characteristics of the subtending leaf at the 2-3rd
and 10-11th fruiting branch (FBN, FB2-3, and FB10-11), and their relationship
with cotton yield and quality, field experiments were conducted using two cotton
cultivars, Kemian 1 and Sumian 15. The results showed that with FBN increasing,
chlorophyll (Chl) components, Pn and non-photochemical quenching (NPQ) in the
subtending leaf significantly declined, while soluble sugar, amino acid and their
ratio (C SS/C AA) as well as F v/F m increased. These results indicated that (1)
non-radiative dissipation of excess light energy at FB2-3 was reduced to improve
solar energy utilization efficiency to compensate for lower Pn, (2) higher NPQ at
FB10-11 played a role in leaf photo-damage avoidance, (3) boll weight was related
to the C SS/C AA ratio rather than carbohydrates content alone, (4) with FBN
increasing, lint biomass and lint/seed ratio increased significantly, but lint
yield decreased due to lower relative amount of bolls, and (5) the decreases in
Pn, sucrose content and C SS /C AA in the subtending leaf at FB2-3 resulted in
lower boll weight and fiber strength.
PMID- 26442061
TI - The heat shock factor gene family in Salix suchowensis: a genome-wide survey and
expression profiling during development and abiotic stresses.
AB - Heat shock transcription factors (Hsfs), which act as important transcriptional
regulatory proteins, play crucial roles in plant developmental processes, and
stress responses. Recently, the genome of the shrub willow Salix suchowensis was
fully sequenced. In this study, a total of 27 non-redundant Hsf genes were
identified from the S. suchowensis genome. Phylogenetic analysis revealed that
the members of the SsuHsf family can be divided into three groups (class A, B,
and C) based on their structural characteristics. Promoter analysis indicated
that the SsuHsfs promoters included various cis-acting elements related to
hormone and/or stress responses. Furthermore, the expression profiles of 27
SsuHsfs were analyzed in different tissues and under various stresses (heat,
drought, salt, and ABA treatment) using RT-PCR. The results demonstrated that the
SsuHsfs were involved in abiotic stress responses. Our results contribute to a
better understanding of the complexity of the SsuHsf gene family, and will
facilitate functional characterization in future studies.
PMID- 26442062
TI - De novo assembly and transcriptome analysis of two contrary tillering mutants to
learn the mechanisms of tillers outgrowth in switchgrass (Panicum virgatum L.).
AB - Tillering is an important trait in monocotyledon plants. The switchgrass (Panicum
virgatum), studied usually as a source of biomass for energy production, can
produce hundreds of tillers in its lifetime. Studying the tillering of
switchgrass also provides information for other monocot crops. High-tillering and
low-tillering mutants were produced by ethyl methanesulfonate mutagenesis.
Alteration of tillering ability resulted from different tiller buds outgrowth in
the two mutants. We sequenced the tiller buds transcriptomes of high-tillering
and low-tillering plants using next-generation sequencing technology, and
generated 34 G data in total. In the de novo assembly results, 133,828 unigenes
were detected with an average length of 1,238 bp, and 5,290 unigenes were
differentially expressed between the two mutants, including 3,225 up-regulated
genes and 2,065 down-regulated genes. Differentially expressed gene analysis with
functional annotations was performed to identify candidate genes involved in
tiller bud outgrowth processes using Gene Ontology classification, Cluster of
Orthologous Groups of proteins, and Kyoto Encyclopedia of Genes and Genomes
pathway analysis. This is the first study to explore the tillering transcriptome
in two types of tillering mutants by de novo sequencing.
PMID- 26442064
TI - In silico study for diversing the molecular pathway of pigment formation: an
alternative to manual coloring in cotton fibers.
AB - Diversity of colors in flowers and fruits is largely due to anthocyanin pigments.
The flavonoid/anthocyanin pathway has been most extensively studied.
Dihydroflavonol 4-reductase (DFR) is a vital enzyme of the flavonoid pathway
which displays major impact on the formation of anthocyanins, flavan 3-ols and
flavonols. The substrate specificity of the DFR was found to play a crucial role
in determination of type of anthocyanidins. Altering the flavonoid/anthocyanin
pathway through genetic engineering to develop color of our own choice is an
exciting subject of future research. In the present study, comparison among four
DFR genes (Gossypium hirsutum, Iris * hollandica, Ang. DFRI and DFRII), sequence
alignment for homology as well as protein modeling and docking is demonstrated.
Estimation of catalytic sites, prediction of substrate preference and protein
docking were the key features of this article. For specific substrate uptake, a
proline rich region and positions 12 plus 26 along with other positions
emphasizing the 26-amino acid residue region (132-157) was tested. Results showed
that proline rich region position 12, 26, and 132-157 plays an important role in
selective attachment of DFRs with respective substrates. Further, "Expasy
ProtParam tool" results showed that Iris * hollandica DFR amino acids (Asn 9: Asp
23) are favorable for reducing DHQ and DHM thus accumulating delphinidin, while
Gossypium hirsutum DFR has (Asn 13: Asp 21) hypothesized to consume DHK. Protein
docking data showed that amino acid residues in above mentioned positions were
just involved in attachment of DFR with substrate and had no role in specific
substrate uptake. Advanced bioinformatics analysis has revealed that all above
mentioned positions have role in substrate attachment. For substrate specificity,
other residues region is involved. It will help in color manipulations in
different plant species.
PMID- 26442063
TI - Plant and pathogen nutrient acquisition strategies.
AB - Nutrients are indispensable elements required for the growth of all living
organisms including plants and pathogens. Phyllosphere, rhizosphere, apoplast,
phloem, xylem, and cell organelles are the nutrient niches in plants that are the
target of bacterial pathogens. Depending upon nutrients availability, the
pathogen adapts various acquisition strategies and inhabits the specific niche.
In this review, we discuss the nutrient composition of different niches in
plants, the mechanisms involved in the recognition of nutrient niche and the
sophisticated strategies used by the bacterial pathogens for acquiring nutrients.
We provide insight into various nutrient acquisition strategies used by
necrotrophic, biotrophic, and hemibiotrophic bacteria. Specifically we discuss
both modulation of bacterial machinery and manipulation of host machinery. In
addition, we highlight the current status of our understanding about the nutrient
acquisition strategies used by bacterial pathogens, namely targeting the sugar
transporters that are dedicated for the plant's growth and development. Bacterial
strategies for altering the plant cell membrane permeability to enhance the
release of nutrients are also enumerated along with in-depth analysis of
molecular mechanisms behind these strategies. The information presented in this
review will be useful to understand the plant-pathogen interaction in nutrient
perspective.
PMID- 26442065
TI - Reactivity and effectiveness of traditional and novel ligands for multi
micronutrient fertilization in a calcareous soil.
AB - This study compares the effectiveness of multi-micronutrient formulations
containing iron (Fe), manganese (Mn), and zinc (Zn) with traditional (EDTA, DTPA,
HEEDTA, and EDDHAm) or novel chelates (o,p-EDDHA, S,S-EDDS, and IDHA) and natural
complexing agents (gluconate and lignosulfonate). The stability and reactivity of
the formulations were studied on batch experiments with calcareous soil and by
speciation modeling. Formulations containing traditional ligands maintained
higher Mn but lower Zn concentration in soil solution than the novel ligands. The
gluconate and lignosulfonate maintained low concentrations of both Mn and Zn in
soil solution. Selected formulations were applied into calcareous soil and their
efficacy was evaluated in a pot experiment with soybean. The formulation
containing DTPA led to the highest Zn concentration in plants, as well as the
formulation containing S,S-EDDS in the short-term, which correlated with its
biodegradability. The application of traditional or novel ligands in formulations
did not result in sufficient plant Mn concentrations, which was related to the
low Mn stability observed for all formulations under moderate oxidation
conditions. The results highlight the need to consider the effect of metals and
ligands interactions in multi-nutrient fertilization and the potential of S,S
EDDS to be used for Zn fertilization. Furthermore, it is necessary to explore new
sources of Mn fertilization for calcareous soils that have greater stability and
efficiency, or instead to use foliar fertilization.
PMID- 26442066
TI - Plant growth conditions alter phytolith carbon.
AB - Many plants, including grasses and some important human food sources, accumulate,
and precipitate silica in their cells to form opaline phytoliths. These
phytoliths contain small amounts of organic matter (OM) that are trapped during
the process of silicification. Previous work has suggested that plant silica is
associated with compounds such as proteins, lipids, lignin, and carbohydrate
complexes. It is not known whether these compounds are cellular components
passively encapsulated as the cell silicifies, polymers actively involved in the
precipitation process or random compounds assimilated by the plant and discarded
into a "glass wastebasket." Here, we used Raman spectroscopy to map the
distribution of OM in phytoliths, and to analyze individual phytoliths isolated
from Sorghum bicolor plants grown under different laboratory treatments. Using
mapping, we showed that OM in phytoliths is distributed throughout the silica and
is not related to dark spots visible in light microscopy, previously assumed to
be the repository for phytolith OM. The Raman spectra exhibited common bands
indicative of C-H stretching modes of general OM, and further more diagnostic
bands consistent with carbohydrates, lignins, and other OM. These Raman spectra
exhibited variability of spectral signatures and of relative intensities between
sample treatments indicating that differing growth conditions altered the
phytolith carbon. This may have strong implications for understanding the
mechanism of phytolith formation, and for use of phytolith carbon isotope values
in dating or paleoclimate reconstruction.
PMID- 26442067
TI - Essentiality of nickel in plants: a role in plant stresses.
AB - The element Ni is considered an essential plant micronutrient because it acts as
an activator of the enzyme urease. Recent studies have shown that Ni may activate
an isoform of glyoxalase I, which performs an important step in the degradation
of methylglyoxal (MG), a potent cytotoxic compound naturally produced by cellular
metabolism. Reduced glutathione (GSH) is consumed and regenerated in the process
of detoxification of MG, which is produced during stress (stress-induced
production). We examine the role of Ni in the relationship between the MG cycle
and GSH homeostasis and suggest that Ni may have a key participation in plant
antioxidant metabolism, especially in stressful situations.
PMID- 26442068
TI - Characterization and expression profile of CaNAC2 pepper gene.
AB - The plant-specific NAC (NAM, ATAF, and CUC) transcription factors have diverse
role in development and stress regulation. A new transcript encoding NAC protein,
homologous to nam-like protein 4 from Petunia was identified from an ABA
regulated subtractive cDNA library of Capsicum annuum seedling. Here, this
homolog (named CaNAC2) from C. annuum was characterized and investigated its role
in abiotic stress tolerance. Our results indicated that a plant-specific and
conserved NAC domain was located in the N-terminus domain of CaNAC2 which was
predicted to encode a polypeptide of 410 amino acids. Phylogenetic analysis
showed that CaNAC2 belonged to the NAC2 subgroup of the orthologous group 4d. The
protein CaNAC2 was subcellularly localized in the nucleus and it had
transcriptional activity in yeast cell. CaNAC2 was expressed mainly in seed and
root. The transcription expression of CaNAC2 was strongly induced by cold, salt
and ABA treatment and inhibited by osmotic stress and SA treatment. Silence of
CaNAC2 in virus-induced gene silenced pepper seedlings resulted in the increased
susceptibility to cold stress and delayed the salt-induced leaf chlorophyll
degradation. These results indicated that this novel CaNAC2 gene might be
involved in pepper response to abiotic stress tolerance.
PMID- 26442069
TI - The impact of fire on the Late Paleozoic Earth system.
AB - Analyses of bulk petrographic data indicate that during the Late Paleozoic
wildfires were more prevalent than at present. We propose that the development of
fire systems through this interval was controlled predominantly by the elevated
atmospheric oxygen concentration (p(O2)) that mass balance models predict
prevailed. At higher levels of p(O2), increased fire activity would have rendered
vegetation with high-moisture contents more susceptible to ignition and would
have facilitated continued combustion. We argue that coal petrographic data
indicate that p(O2) rather than global temperatures or climate, resulted in the
increased levels of wildfire activity observed during the Late Paleozoic and can,
therefore, be used to predict it. These findings are based upon analyses of
charcoal volumes in multiple coals distributed across the globe and deposited
during this time period, and that were then compared with similarly diverse
modern peats and Cenozoic lignites and coals. Herein, we examine the
environmental and ecological factors that would have impacted fire activity and
we conclude that of these factors p(O2) played the largest role in promoting
fires in Late Paleozoic peat-forming environments and, by inference, ecosystems
generally, when compared with their prevalence in the modern world.
PMID- 26442071
TI - Partially dissecting the steady-state electron fluxes in Photosystem I in wild
type and pgr5 and ndh mutants of Arabidopsis.
AB - Cyclic electron flux (CEF) around Photosystem I (PS I) is difficult to quantify.
We obtained the linear electron flux (LEFO2) through both photosystems and the
total electron flux through PS I (ETR1) in Arabidopsis in CO2-enriched air.
DeltaFlux = ETR1 - LEFO2 is an upper estimate of CEF, which consists of two
components, an antimycin A-sensitive, PGR5 (proton gradient regulation 5 protein)
dependent component and an insensitive component facilitated by a chloroplastic
nicotinamide adenine dinucleotide dehydrogenase-like complex (NDH). Using wild
type as well as pgr5 and ndh mutants, we observed that (1) 40% of the absorbed
light was partitioned to PS I; (2) at high irradiance a substantial antimycin A
sensitive CEF occurred in the wild type and the ndh mutant; (3) at low irradiance
a sizable antimycin A-sensitive CEF occurred in the wild type but not in the ndh
mutant, suggesting an enhancing effect of NDH in low light; and (4) in the pgr5
mutant, and the wild type and ndh mutant treated with antimycin A, a residual
DeltaFlux existed at high irradiance, attributable to charge recombination and/or
pseudo-cyclic electron flow. Therefore, in low-light-acclimated plants exposed to
high light, DeltaFlux has contributions from various paths of electron flow
through PS I.
PMID- 26442070
TI - Importance of Mediator complex in the regulation and integration of diverse
signaling pathways in plants.
AB - Basic transcriptional machinery in eukaryotes is assisted by a number of
cofactors, which either increase or decrease the rate of transcription. Mediator
complex is one such cofactor, and recently has drawn a lot of interest because of
its integrative power to converge different signaling pathways before channeling
the transcription instructions to the RNA polymerase II machinery. Like yeast and
metazoans, plants do possess the Mediator complex across the kingdom, and its
isolation and subunit analyses have been reported from the model plant,
Arabidopsis. Genetic, and molecular analyses have unraveled important regulatory
roles of Mediator subunits at every stage of plant life cycle starting from
flowering to embryo and organ development, to even size determination. It also
contributes immensely to the survival of plants against different environmental
vagaries by the timely activation of its resistance mechanisms. Here, we have
provided an overview of plant Mediator complex starting from its discovery to
regulation of stoichiometry of its subunits. We have also reviewed involvement of
different Mediator subunits in different processes and pathways including defense
response pathways evoked by diverse biotic cues. Wherever possible, attempts have
been made to provide mechanistic insight of Mediator's involvement in these
processes.
PMID- 26442072
TI - Silicon enhanced salt tolerance by improving the root water uptake and decreasing
the ion toxicity in cucumber.
AB - Although the effects of silicon application on enhancing plant salt tolerance
have been widely investigated, the underlying mechanism has remained unclear. In
this study, seedlings of cucumber, a medium silicon accumulator plant, grown in
0.83 mM silicon solution for 2 weeks were exposed to 65 mM NaCl solution for
another 1 week. The dry weight and shoot/root ratio were reduced by salt stress,
but silicon application significantly alleviated these decreases. The chlorophyll
concentration, net photosynthetic rate, transpiration rate and leaf water content
were higher in plants treated with silicon than in untreated plants under salt
stress conditions. Further investigation showed that salt stress decreased root
hydraulic conductance (Lp), but that silicon application moderated this salt
induced decrease in Lp. The higher Lp in silicon-treated plants may account for
the superior plant water balance. Moreover, silicon application significantly
decreased Na(+) concentration in the leaves while increasing K(+) concentration.
Simultaneously, both free and conjugated types of polyamines were maintained at
high levels in silicon-treated plants, suggesting that polyamines may be involved
in the ion toxicity. Our results indicate that silicon enhances the salt
tolerance of cucumber through improving plant water balance by increasing the Lp
and reducing Na(+) content by increasing polyamine accumulation.
PMID- 26442073
TI - Modulation of phenolic metabolism under stress conditions in a Lotus japonicus
mutant lacking plastidic glutamine synthetase.
AB - This paper was aimed to investigate the possible implications of the lack of
plastidic glutamine synthetase (GS2) in phenolic metabolism during stress
responses in the model legume Lotus japonicus. Important changes in the
transcriptome were detected in a GS2 mutant called Ljgln2-2, compared to the wild
type, in response to two separate stress conditions, such as drought or the
result of the impairment of the photorespiratory cycle. Detailed transcriptomic
analysis showed that the biosynthesis of phenolic compounds was affected in the
mutant plants in these two different types of stress situations. For this reason,
the genes and metabolites related to this metabolic route were further
investigated using a combined approach of gene expression analysis and metabolite
profiling. A high induction of the expression of several genes for the
biosynthesis of different branches of the phenolic biosynthetic pathway was
detected by qRT-PCR. The extent of induction was always higher in Ljgln2-2,
probably reflecting the higher stress levels present in this genotype. This was
paralleled by accumulation of several kaempferol and quercetine glycosides, some
of them described for the first time in L. japonicus, and of high levels of the
isoflavonoid vestitol. The results obtained indicate that the absence of GS2
affects different aspects of phenolic metabolism in L. japonicus plants in
response to stress.
PMID- 26442074
TI - Specialization for resistance in wild host-pathogen interaction networks.
AB - Properties encompassed by host-pathogen interaction networks have potential to
give valuable insight into the evolution of specialization and coevolutionary
dynamics in host-pathogen interactions. However, network approaches have been
rarely utilized in previous studies of host and pathogen phenotypic variation.
Here we applied quantitative analyses to eight networks derived from spatially
and temporally segregated host (Linum marginale) and pathogen (Melampsora lini)
populations. First, we found that resistance strategies are highly variable
within and among networks, corresponding to a spectrum of specialist and
generalist resistance types being maintained within all networks. At the
individual level, specialization was strongly linked to partial resistance, such
that partial resistance was effective against a greater number of pathogens
compared to full resistance. Second, we found that all networks were
significantly nested. There was little support for the hypothesis that temporal
evolutionary dynamics may lead to the development of nestedness in host-pathogen
infection networks. Rather, the common patterns observed in terms of nestedness
suggests a universal driver (or multiple drivers) that may be independent of
spatial and temporal structure. Third, we found that resistance networks were
significantly modular in two spatial networks, clearly reflecting spatial and
ecological structure within one of the networks. We conclude that (1) overall
patterns of specialization in the networks we studied mirror evolutionary trade
offs with the strength of resistance; (2) that specific network architecture can
emerge under different evolutionary scenarios; and (3) network approaches offer
great utility as a tool for probing the evolutionary and ecological genetics of
host-pathogen interactions.
PMID- 26442075
TI - Investigation of the multifunctional gene AOP3 expands the regulatory network
fine-tuning glucosinolate production in Arabidopsis.
AB - Quantitative trait loci (QTL) mapping studies enable identification of loci that
are part of regulatory networks controlling various phenotypes. Detailed
investigations of genes within these loci are required to ultimately understand
the function of individual genes and how they interact with other players in the
network. In this study, we use transgenic plants in combination with natural
variation to investigate the regulatory role of the AOP3 gene found in GS-AOP
locus previously suggested to contribute to the regulation of glucosinolate
defense compounds. Phenotypic analysis and QTL mapping in F2 populations with
different AOP3 transgenes support that the enzymatic function and the AOP3 RNA
both play a significant role in controlling glucosinolate accumulation.
Furthermore, we find different loci interacting with either the enzymatic
activity or the RNA of AOP3 and thereby extend the regulatory network controlling
glucosinolate accumulation.
PMID- 26442077
TI - Design of an F1 hybrid breeding strategy for ryegrasses based on selection of
self-incompatibility locus-specific alleles.
AB - Relatively modest levels of genetic gain have been achieved in conventional
ryegrass breeding when compared to cereal crops such as maize, current estimates
indicating an annual improvement of 0.25-0.6% in dry matter production. This
property is partially due to an inability to effectively exploit heterosis
through the formation of F1 hybrids. Controlled crossing of ryegrass lines from
geographically distant origins has demonstrated the occurrence of heterosis,
which can result in increases of dry matter production in the order of 25%.
Although capture of hybrid vigor offers obvious advantages for ryegrass cultivar
production, to date there have been no effective and commercially suitable
methods for obtaining high proportions of F1 hybrid seed. Continued advances in
fine-scale genetic and physical mapping of the gametophytic self-incompatibility
(SI) loci (S and Z) of ryegrasses are likely in the near future to permit the
identification of closely linked genetic markers that define locus-specific
haplotypes, allowing prediction of allelic variants and hence compatibility
between different plant genotypes. Given the availability of such information, a
strategy for efficient generation of ryegrass cultivars with a high proportion of
F1 hybrid individuals has been simulated, which is suitable for commercial
implementation. Through development of two parental pools with restricted
diversity at the SI loci, relative crossing compatibility between pools is
increased. Based on simulation of various levels of SI allele diversity
restriction, the most effective scheme will generate 83.33% F1 hybrids. Results
from the study, including the impact of varying flowering time, are discussed
along with a proposed breeding design for commercial application.
PMID- 26442076
TI - Genome-wide gene expression perturbation induced by loss of C2 chromosome in
allotetraploid Brassica napus L.
AB - Aneuploidy with loss of entire chromosomes from normal complement disrupts the
balanced genome and is tolerable only by polyploidy plants. In this study, the
monosomic and nullisomic plants losing one or two copies of C2 chromosome from
allotetraploid Brassica napus L. (2n = 38, AACC) were produced and compared for
their phenotype and transcriptome. The monosomics gave a plant phenotype very
similar to the original donor, but the nullisomics had much smaller stature and
also shorter growth period. By the comparative analyses on the global transcript
profiles with the euploid donor, genome-wide alterations in gene expression were
revealed in two aneuploids, and their majority of differentially expressed genes
(DEGs) resulted from the trans-acting effects of the zero and one copy of C2
chromosome. The higher number of up-regulated genes than down-regulated genes on
other chromosomes suggested that the genome responded to the C2 loss via
enhancing the expression of certain genes. Particularly, more DEGs were detected
in the monosomics than nullisomics, contrasting with their phenotypes. The gene
expression of the other chromosomes was differently affected, and several
dysregulated domains in which up- or downregulated genes obviously clustered were
identifiable. But the mean gene expression (MGE) for homoeologous chromosome A2
reduced with the C2 loss. Some genes and their expressions on C2 were correlated
with the phenotype deviations in the aneuploids. These results provided new
insights into the transcriptomic perturbation of the allopolyploid genome
elicited by the loss of individual chromosome.
PMID- 26442078
TI - Extracellular vesicles including exosomes in cross kingdom regulation: a
viewpoint from plant-fungal interactions.
PMID- 26442079
TI - ROS mediated MAPK signaling in abiotic and biotic stress- striking similarities
and differences.
AB - Plants encounter a number of environmental stresses throughout their life cycles,
most of which activate mitogen activated protein kinase (MAPK) pathway. The MAPKs
show crosstalks at several points but the activation and the final response is
known to be specific for particular stimuli that in-turn activates specific set
of downstream targets. Interestingly, reactive oxygen species (ROS) is an
important and common messenger produced in various environmental stresses and is
known to activate many of the MAPKs. ROS activates a similar MAPK in different
environmental stimuli, showing different downstream targets with different and
specific responses. In animals and yeast, the mechanism behind the specific
activation of MAPK by different concentration and species of ROS is elaborated,
but in plants this aspect is still unclear. This review mainly focuses on the
aspect of specificity of ROS mediated MAPK activation. Attempts have been made to
review the involvement of ROS in abiotic stress mediated MAPK signaling and how
it differentiates with that of biotic stress.
PMID- 26442080
TI - Computational analyses of ancient pathogen DNA from herbarium samples: challenges
and prospects.
AB - The application of DNA sequencing technology to the study of ancient DNA has
enabled the reconstruction of past epidemics from genomes of historically
important plant-associated microbes. Recently, the genome sequences of the potato
late blight pathogen Phytophthora infestans were analyzed from 19th century
herbarium specimens. These herbarium samples originated from infected potatoes
collected during and after the Irish potato famine. Herbaria have therefore great
potential to help elucidate past epidemics of crops, date the emergence of
pathogens, and inform about past pathogen population dynamics. DNA preservation
in herbarium samples was unexpectedly good, raising the possibility of a whole
new research area in plant and microbial genomics. However, the recovered DNA can
be extremely fragmented resulting in specific challenges in reconstructing genome
sequences. Here we review some of the challenges in computational analyses of
ancient DNA from herbarium samples. We also applied the recently developed
linkage method to haplotype reconstruction of diploid or polyploid genomes from
fragmented ancient DNA.
PMID- 26442081
TI - Comparative genomic analysis of duplicated homoeologous regions involved in the
resistance of Brassica napus to stem canker.
AB - All crop species are current or ancient polyploids. Following whole genome
duplication, structural and functional modifications result in differential gene
content or regulation in the duplicated regions, which can play a fundamental
role in the diversification of genes underlying complex traits. We have
investigated this issue in Brassica napus, a species with a highly duplicated
genome, with the aim of studying the structural and functional organization of
duplicated regions involved in quantitative resistance to stem canker, a disease
caused by the fungal pathogen Leptosphaeria maculans. Genome-wide association
analysis on two oilseed rape panels confirmed that duplicated regions of
ancestral blocks E, J, R, U, and W were involved in resistance to stem canker.
The structural analysis of the duplicated genomic regions showed a higher gene
density on the A genome than on the C genome and a better collinearity between
homoeologous regions than paralogous regions, as overall in the whole B. napus
genome. The three ancestral sub-genomes were involved in the resistance to stem
canker and the fractionation profile of the duplicated regions corresponded to
what was expected from results on the B. napus progenitors. About 60% of the
genes identified in these duplicated regions were single-copy genes while less
than 5% were retained in all the duplicated copies of a given ancestral block.
Genes retained in several copies were mainly involved in response to stress,
signaling, or transcription regulation. Genes with resistance-associated markers
were mainly retained in more than two copies. These results suggested that some
genes underlying quantitative resistance to stem canker might be duplicated
genes. Genes with a hydrolase activity that were retained in one copy or R-like
genes might also account for resistance in some regions. Further analyses need to
be conducted to indicate to what extent duplicated genes contribute to the
expression of the resistance phenotype.
PMID- 26442082
TI - Genome-wide analysis and expression profiling under heat and drought treatments
of HSP70 gene family in soybean (Glycine max L.).
AB - Heat shock proteins (HSPs) perform a fundamental role in protecting plants
against abiotic stresses. Previous studies have made great efforts in the
functional analysis of individual family members, but there has not yet been an
overall analysis or expression profiling of the HSP70 gene family in soybeans
(Glycine max L.). In this study, an investigation of the soybean genome revealed
61 putative HSP70 genes, which were evaluated. These genes were classified into
eight sub-families, denoted I-VIII, based on a phylogenetic analysis. In each sub
family, the constituent parts of the gene structure and motif were relatively
conserved. These GmHSP70 genes were distributed unequally on 17 of the 20
chromosomes. The analysis of the expression profiles showed that 53 of the 61
GmHSP70 genes were differentially expressed across the 14 tissues. However, most
of the GmHSP70s were differentially expressed in a tissue-specific expression
pattern. Furthermore, the expression of some of the duplicate genes was partially
redundant, while others showed functional diversity. The quantitative real-time
PCR (qRT-PCR) analysis of the 61 soybean HSP70 genes confirmed their stress
inducible expression patterns under both drought and heat stress. These findings
provide a thorough overview of the evolution and modification of the GmHSP70 gene
family, which will help to determine the functional characteristics of the HSP70
genes in soybean growth and development.
PMID- 26442083
TI - The effects of bacterial volatile emissions on plant abiotic stress tolerance.
AB - Plant growth-promoting rhizobacteria (PGPR) are beneficial plant symbionts that
have been successfully used in agriculture to increase seedling emergence, plant
weight, crop yield, and disease resistance. Some PGPR strains release volatile
organic compounds (VOCs) that can directly and/or indirectly mediate increases in
plant biomass, disease resistance, and abiotic stress tolerance. This mini-review
focuses on the enhancement of plant abiotic stress tolerance by bacterial VOCs.
The review considers how PGPR VOCs induce tolerance to salinity and drought
stress and also how they improve sulfur and iron nutrition in plants. The
potential complexities in evaluating the effects of PGPR VOCs are also discussed.
PMID- 26442084
TI - How and why do root apices sense light under the soil surface?
AB - Light can penetrate several centimeters below the soil surface. Growth,
development and behavior of plant roots are markedly affected by light despite
their underground lifestyle. Early studies provided contrasting information on
the spatial and temporal distribution of light-sensing cells in the apical region
of root apex and discussed the physiological roles of plant hormones in root
responses to light. Recent biological and microscopic advances have improved our
understanding of the processes involved in the sensing and transduction of light
signals, resulting in subsequent physiological and behavioral responses in
growing root apices. Here, we review current knowledge of cellular distributions
of photoreceptors and their signal transduction pathways in diverse root tissues
and root apex zones. We are discussing also the roles of auxin transporters in
roots exposed to light, as well as interactions of light signal perceptions with
sensing of other environmental factors relevant to plant roots.
PMID- 26442085
TI - Common protein sequence signatures associate with Sclerotinia borealis lifestyle
and secretion in fungal pathogens of the Sclerotiniaceae.
AB - Fungal plant pathogens produce secreted proteins adapted to function outside
fungal cells to facilitate colonization of their hosts. In many cases such as for
fungi from the Sclerotiniaceae family the repertoire and function of secreted
proteins remains elusive. In the Sclerotiniaceae, whereas Sclerotinia
sclerotiorum and Botrytis cinerea are cosmopolitan broad host-range plant
pathogens, Sclerotinia borealis has a psychrophilic lifestyle with a low optimal
growth temperature, a narrow host range and geographic distribution. To spread
successfully, S. borealis must synthesize proteins adapted to function in its
specific environment. The search for signatures of adaptation to S. borealis
lifestyle may therefore help revealing proteins critical for colonization of the
environment by Sclerotiniaceae fungi. Here, we analyzed amino acids usage and
intrinsic protein disorder in alignments of groups of orthologous proteins from
the three Sclerotiniaceae species. We found that enrichment in Thr, depletion in
Glu and Lys, and low disorder frequency in hot loops are significantly associated
with S. borealis proteins. We designed an index to report bias in these
properties and found that high index proteins were enriched among secreted
proteins in the three Sclerotiniaceae fungi. High index proteins were also
enriched in function associated with plant colonization in S. borealis, and in in
planta-induced genes in S. sclerotiorum. We highlight a novel putative antifreeze
protein and a novel putative lytic polysaccharide monooxygenase identified
through our pipeline as candidate proteins involved in colonization of the
environment. Our findings suggest that similar protein signatures associate with
S. borealis lifestyle and with secretion in the Sclerotiniaceae. These signatures
may be useful for identifying proteins of interest as targets for the management
of plant diseases.
PMID- 26442086
TI - Identification and characterization of miRNAs in ripening fruit of Lycium
barbarum L. using high-throughput sequencing.
AB - MicroRNAs (miRNAs) are master regulators of gene activity documented to play
central roles in fruit ripening in model plant species, yet little is known of
their roles in Lycium barbarum L. fruits. In this study, miRNA levels in L.
barbarum fruit samples at four developmental stages, were assayed using Illumina
HiSeqTM2000. This revealed the presence of 50 novel miRNAs and 38 known miRNAs in
L. barbarum fruits. Of the novel miRNAs, 36 were specific to L. barbarum fruits
compared with L. chinense. A number of stage-specific miRNAs were identified and
GO terms were assigned to 194 unigenes targeted by miRNAs. The majority of GO
terms of unigenes targeted by differentially expressed miRNAs are "intracellular
organelle," "binding," "metabolic process," "pigmentation," and "biological
regulation." Enriched KEGG analysis indicated that nucleotide excision repair and
ubiquitin mediated proteolysis were over-represented during the initial stage of
ripening, with ABC transporters and sulfur metabolism pathways active during the
middle stages and ABC transporters and spliceosome enriched in the final stages
of ripening. Several miRNAs and their targets serving as potential regulators in
L. barbarum fruit ripening were identified using quantitative reverse
transcription polymerase chain reaction. The miRNA-target interactions were
predicted for L. barbarum ripening regulators including miR156/157 with LbCNR and
LbWRKY8, and miR171 with LbGRAS. Additionally, regulatory interactions
potentially controlling fruit quality and nutritional value via sugar and
secondary metabolite accumulation were identified. These include miR156 targeting
of fructokinase and 1-deoxy-D-xylulose-5-phosphate synthase and miR164 targeting
of beta-fructofuranosidase. In sum, valuable information revealed by small RNA
sequencing in this study will provide a solid foundation for uncovering the miRNA
mediated mechanism of fruit ripening and quality in this nutritional food.
PMID- 26442087
TI - Influence of stripe rust infection on the photosynthetic characteristics and
antioxidant system of susceptible and resistant wheat cultivars at the adult
plant stage.
AB - Wheat stripe rust (Puccinia striiformis f. sp. tritici, Pst), is one of the most
serious diseases of wheat (Triticum aestivum L.) worldwide. To gain a better
understanding of the protective mechanism against stripe rust at the adult plant
stage, the differences in photosystem II and antioxidant enzymatic systems
between susceptible and resistant wheat in response to stripe rust disease (P.
striiformis) were investigated. We found that chlorophyll fluorescence and the
activities of the antioxidant enzymes were higher in resistant wheat than in
susceptible wheat after stripe rust infection. Compared with the susceptible
wheat, the resistant wheat accumulated a higher level of D1 protein and a lower
level of reactive oxygen species after infection. Furthermore, our results
demonstrate that D1 and light-harvesting complex II (LHCII) phosphorylation are
involved in the resistance to stripe rust in wheat. The CP29 protein was
phosphorylated under stripe rust infection, like its phosphorylation in other
monocots under environmental stresses. More extensive damages occur on the
thylakoid membranes in the susceptible wheat compared with the resistant wheat.
The findings provide evidence that thylakoid protein phosphorylation and
antioxidant enzyme systems play important roles in plant responses and defense to
biotic stress.
PMID- 26442088
TI - Genome-wide identification and transcriptional expression analysis of mitogen
activated protein kinase and mitogen-activated protein kinase kinase genes in
Capsicum annuum.
AB - The tripartite mitogen-activated protein kinase (MAPK) signaling cascades have
been implicated in plant growth, development, and environment adaptation, but a
comprehensive understanding of MAPK signaling at genome-wide level is limited in
Capsicum annuum. Herein, genome-wide identification and transcriptional
expression analysis of MAPK and MAPK kinase (MAPKK) were performed in pepper. A
total of 19 pepper MAPK (CaMAPKs) genes and five MAPKK (CaMAPKKs) genes were
identified. Phylogenetic analysis indicated that CaMAPKs and CaMAPKKs could be
classified into four groups and each group contains similar exon-intron
structures. However, significant divergences were also found. Notably, five
members of the pepper MAPKK family were much less conserved than those found in
Arabidopsis, and 9 Arabidopsis MAPKs did not have orthologs in pepper.
Additionally, 7 MAPKs in Arabidopsis had either two or three orthologs in the
pepper genome, and six pepper MAPKs and one MAPKK differing in sequence were
found in three pepper varieties. Quantitative real-time RT-PCR analysis showed
that the majority of MAPK and MAPKK genes were ubiquitously expressed and
transcriptionally modified in pepper leaves after treatments with heat, salt, and
Ralstonia solanacearum inoculation as well as exogenously applied salicylic acid,
methyl jasmonate, ethephon, and abscisic acid. The MAPKK-MAPK interactome was
tested by yeast two-hybrid assay, the results showed that one MAPKK might
interact with multiple MAPKs, one MAPK might also interact with more than one
MAPKKs, constituting MAPK signaling networks which may collaborate in
transmitting upstream signals into appropriate downstream cellular responses and
processes. These results will facilitate future functional characterization of
MAPK cascades in pepper.
PMID- 26442089
TI - Mitochondrial pleomorphy in plant cells is driven by contiguous ER dynamics.
AB - Mitochondria are pleomorphic, double membrane-bound organelles involved in
cellular energetics in all eukaryotes. Mitochondria in animal and yeast cells are
typically tubular-reticulate structures and several micro-meters long but in
green plants they are predominantly observed as 0.2-1.5 MUm punctae. While
fission and fusion, through the coordinated activity of several conserved
proteins, shapes mitochondria, the endoplasmic reticulum (ER) has recently been
identified as an additional player in this process in yeast and mammalian cells.
The mitochondria-ER relationship in plant cells remains largely uncharacterized.
Here, through live-imaging of the entire range of mitochondria pleomorphy we
uncover the underlying basis for the predominantly punctate mitochondrial form in
plants. We demonstrate that mitochondrial morphology changes in response to light
and cytosolic sugar levels in an ER mediated manner. Whereas, large ER polygons
and low dynamics under dark conditions favor mitochondrial fusion and elongation,
small ER polygons result in increased fission and predominantly small
mitochondria. Hypoxia also reduces ER dynamics and increases mitochondrial fusion
to produce giant mitochondria. By observing elongated mitochondria in normal
plants and fission-impaired Arabidopsis nmt1-2 and drp3a mutants we also
establish that thin extensions called matrixules and a beads-on-a-string
mitochondrial phenotype are direct consequences of mitochondria-ER interactions.
PMID- 26442090
TI - Mining the phytomicrobiome to understand how bacterial coinoculations enhance
plant growth.
AB - In previous work, we showed that coinoculating Rhizobium leguminosarum bv. viciae
128C53 and Bacillus simplex 30N-5 onto Pisum sativum L. roots resulted in better
nodulation and increased plant growth. We now expand this research to include
another alpha-rhizobial species as well as a beta-rhizobium, Burkholderia tuberum
STM678. We first determined whether the rhizobia were compatible with B. simplex
30N-5 by cross-streaking experiments, and then Medicago truncatula and Melilotus
alba were coinoculated with B. simplex 30N-5 and Sinorhizobium (Ensifer) meliloti
to determine the effects on plant growth. Similarly, B. simplex 30N-5 and Bu.
tuberum STM678 were coinoculated onto Macroptilium atropurpureum. The exact
mechanisms whereby coinoculation results in increased plant growth are
incompletely understood, but the synthesis of phytohormones and siderophores, the
improved solubilization of inorganic nutrients, and the production of
antimicrobial compounds are likely possibilities. Because B. simplex 30N-5 is not
widely recognized as a Plant Growth Promoting Bacterial (PGPB) species, after
sequencing its genome, we searched for genes proposed to promote plant growth,
and then compared these sequences with those from several well studied PGPB
species. In addition to genes involved in phytohormone synthesis, we detected
genes important for the production of volatiles, polyamines, and antimicrobial
peptides as well as genes for such plant growth-promoting traits as phosphate
solubilization and siderophore production. Experimental evidence is presented to
show that some of these traits, such as polyamine synthesis, are functional in B.
simplex 30N-5, whereas others, e.g., auxin production, are not.
PMID- 26442091
TI - Enhanced tomato disease resistance primed by arbuscular mycorrhizal fungus.
AB - Roots of most terrestrial plants form symbiotic associations (mycorrhiza) with
soil- borne arbuscular mycorrhizal fungi (AMF). Many studies show that
mycorrhizal colonization enhances plant resistance against pathogenic fungi.
However, the mechanism of mycorrhiza-induced disease resistance remains
equivocal. In this study, we found that mycorrhizal inoculation with AMF
Funneliformis mosseae significantly alleviated tomato (Solanum lycopersicum
Mill.) early blight disease caused by Alternaria solani Sorauer. AMF pre
inoculation led to significant increases in activities of beta-1,3-glucanase,
chitinase, phenylalanine ammonia-lyase (PAL) and lipoxygenase (LOX) in tomato
leaves upon pathogen inoculation. Mycorrhizal inoculation alone did not influence
the transcripts of most genes tested. However, pathogen attack on AMF-inoculated
plants provoked strong defense responses of three genes encoding pathogenesis
related proteins, PR1, PR2, and PR3, as well as defense-related genes LOX, AOC,
and PAL, in tomato leaves. The induction of defense responses in AMF pre
inoculated plants was much higher and more rapid than that in un-inoculated
plants in present of pathogen infection. Three tomato genotypes: a Castlemart
wild-type (WT) plant, a jasmonate (JA) biosynthesis mutant (spr2), and a
prosystemin-overexpressing 35S::PS plant were used to examine the role of the JA
signaling pathway in AMF-primed disease defense. Pathogen infection on
mycorrhizal 35S::PS plants led to higher induction of defense-related genes and
enzymes relative to WT plants. However, pathogen infection did not induce these
genes and enzymes in mycorrhizal spr2 mutant plants. Bioassays showed that
35S::PS plants were more resistant and spr2 plants were more susceptible to early
blight compared with WT plants. Our finding indicates that mycorrhizal
colonization enhances tomato resistance to early blight by priming systemic
defense response, and the JA signaling pathway is essential for mycorrhiza-primed
disease resistance.
PMID- 26442092
TI - Recent advances in understanding carotenoid-derived signaling molecules in
regulating plant growth and development.
AB - Carotenoids (C40) are synthesized in plastids and perform numerous important
functions in these organelles. In addition, carotenoids can be processed into
smaller signaling molecules that regulate various phases of the plant's life
cycle. Besides the relatively well-studied phytohormones abscisic acid (ABA) and
strigolactones (SLs), additional carotenoid-derived signaling molecules have been
discovered and shown to regulate plant growth and development. As a few excellent
reviews summarized recent research on ABA and SLs, this mini review will focus on
progress made on identification and characterization of the emerging carotenoid
derived signals. Overall, a better understanding of carotenoid-derived signaling
molecules has immediate applications in improving plant biomass production which
in turn will have far reaching impacts on providing food, feed, and fuel for the
growing world population.
PMID- 26442094
TI - How spatio-temporal habitat connectivity affects amphibian genetic structure.
AB - Heterogeneous landscapes and fluctuating environmental conditions can affect
species dispersal, population genetics, and genetic structure, yet understanding
how biotic and abiotic factors affect population dynamics in a fluctuating
environment is critical for species management. We evaluated how spatio-temporal
habitat connectivity influences dispersal and genetic structure in a population
of boreal chorus frogs (Pseudacris maculata) using a landscape genetics approach.
We developed gravity models to assess the contribution of various factors to the
observed genetic distance as a measure of functional connectivity. We selected
(a) wetland (within-site) and (b) landscape matrix (between-site)
characteristics; and (c) wetland connectivity metrics using a unique methodology.
Specifically, we developed three networks that quantify wetland connectivity
based on: (i) P. maculata dispersal ability, (ii) temporal variation in wetland
quality, and (iii) contribution of wetland stepping-stones to frog dispersal. We
examined 18 wetlands in Colorado, and quantified 12 microsatellite loci from 322
individual frogs. We found that genetic connectivity was related to topographic
complexity, within- and between-wetland differences in moisture, and wetland
functional connectivity as contributed by stepping-stone wetlands. Our results
highlight the role that dynamic environmental factors have on dispersal-limited
species and illustrate how complex asynchronous interactions contribute to the
structure of spatially-explicit metapopulations.
PMID- 26442093
TI - Cyclic electron flow provides acclimatory plasticity for the photosynthetic
machinery under various environmental conditions and developmental stages.
AB - Photosynthetic electron flow operates in two modes, linear and cyclic. In cyclic
electron flow (CEF), electrons are recycled around photosystem I. As a result, a
transthylakoid proton gradient (DeltapH) is generated, leading to the production
of ATP without concomitant production of NADPH, thus increasing the ATP/NADPH
ratio within the chloroplast. At least two routes for CEF exist: a PROTON
GRADIENT REGULATION5-PGRL1-and a chloroplast NDH-like complex mediated pathway.
This review focuses on recent findings concerning the characteristics of both CEF
routes in higher plants, with special emphasis paid on the crucial role of CEF in
under challenging environmental conditions and developmental stages.
PMID- 26442095
TI - An introductory review of parallel independent component analysis (p-ICA) and a
guide to applying p-ICA to genetic data and imaging phenotypes to identify
disease-associated biological pathways and systems in common complex disorders.
AB - Complex inherited phenotypes, including those for many common medical and
psychiatric diseases, are most likely underpinned by multiple genes contributing
to interlocking molecular biological processes, along with environmental factors
(Owen et al., 2010). Despite this, genotyping strategies for complex, inherited,
disease-related phenotypes mostly employ univariate analyses, e.g., genome wide
association. Such procedures most often identify isolated risk-related SNPs or
loci, not the underlying biological pathways necessary to help guide the
development of novel treatment approaches. This article focuses on the
multivariate analysis strategy of parallel (i.e., simultaneous combination of SNP
and neuroimage information) independent component analysis (p-ICA), which
typically yields large clusters of functionally related SNPs statistically
correlated with phenotype components, whose overall molecular biologic relevance
is inferred subsequently using annotation software suites. Because this is a
novel approach, whose details are relatively new to the field we summarize its
underlying principles and address conceptual questions regarding interpretation
of resulting data and provide practical illustrations of the method.
PMID- 26442096
TI - Evolution of TERT-interacting lncRNAs: expanding the regulatory landscape of
telomerase.
AB - Long non-coding RNAs (lncRNAs) evolve rapidly and are functionally diverse. The
emergence of new lncRNAs is driven by genome disturbance events, including whole
genome duplication, and transposition. One of the few lncRNAs with a conserved
role throughout eukaryotes is the telomerase RNA, TER. TER works in concert with
the telomerase reverse transcriptase (TERT) to maintain telomeres. Here we
discuss recent findings from Arabidopsis thaliana and its relatives illustrating
the remarkable evolutionary flexibility within TER and the potential for non
canonical TERT-lncRNA interactions. We highlight the two TERs in A. thaliana. One
is a conventional telomerase template. The other lncRNA negatively regulates
telomerase activity in response to DNA damage, a function mediated by co-option
of a transposable element. In addition, we discuss evidence for multiple
independent TER loci throughout the plant family Brassicaceae, and how these loci
not only reflect rapid convergent evolution, but also the flexibility of having a
lncRNA at the core of telomerase. Lastly, we discuss the propensity for TERT to
bind a suite of non-templating lncRNAs, and how such RNAs may facilitate
telomerase regulation and off-telomere functions.
PMID- 26442098
TI - Changing values of farm animal genomic resources. from historical breeds to the
Nagoya Protocol.
AB - The paper reviews the history of Animal genetic resources (AnGRs) and claims that
over the course of history they have been conceptually transformed from economic,
ecologic and scientific life forms into political objects, reflecting in the way
in which any valuation of AnGRs is today inherently imbued with national politics
and its values enacted by legally binding global conventions. Historically, the
first calls to conservation were based on the economic, ecological and scientific
values of the AnGR. While the historical arguments are valid and still commonly
proposed values for conservation, the AnGR have become highly politicized since
the adoption of the Convention of Biological Diversity (CBD), the subsequent
Interlaken Declaration, the Global Plan for Action (GPA) and the Nagoya Protocol.
The scientific and political definitions of the AnGRs were creatively reshuffled
within these documents and the key criteria by which they are now identified and
valued today were essentially redefined. The criteria of "in situ condition" has
become the necessary starting point for all valuation efforts of AnGRs,
effectively transforming their previous nature as natural property and global
genetic commons into objects of national concern pertaining to territorially
discrete national genetic landscapes, regulated by the sovereign powers of the
parties to the global conventions.
PMID- 26442097
TI - Polymorphisms in Toll-like receptor genes are associated with vitiligo.
AB - BACKGROUND: The members of Toll-like receptor (TLR) family are responsible for
recognizing various molecular patterns associated with pathogens. Their
expression is not confined to immune cells and have been detected in skin cells
such as keratinocytes and melanocytes. As part of a generated response to
pathogens, TLRs are involved in inducing inflammatory mediators to combat these
threats. It is therefore not surprising that TLRs have been implicated in
inflammatory skin diseases, including atopic dermatitis and psoriasis. Likewise,
as key players in autoimmunity, they have been associated with a number of
autoimmune diseases. Based on this, the role of TLRs in vitiligo could be
suspected, but is yet to be clearly established. METHODS: In order to conduct a
genetic association analysis, 30 SNPs were selected from TLR1-TLR8 and TLR10
regions to be genotyped in Estonian case-control cohort consisting of 139
vitiligo patients and 307 healthy control individuals. The patients were further
analyzed in subgroups based on sex, age of onset, occurrence of vitiligo among
relatives, extent of depigmented areas, vitiligo progression activity, appearance
of Kobner's phenomenon, existence of halo naevi, and incidence of spontaneous
repigmentation. RESULTS: The most notable finding came with SNP rs179020 situated
in TLR7 gene, that was associated in entire vitiligo (Padj = 0.0065) and also
several subgroup analyses. Other single marker and haplotype analyses pointed to
TLR3, TLR4, and TLR10 genes. CONCLUSIONS: This study investigated the genetic
regions of nine TLR genes in relation to vitiligo susceptibility. The main
results were the associations of TLR7 SNPs with vitiligo, while several other
associations were obtained from the remaining TLR gene regions. This suggests
that in addition to other inflammatory skin diseases, TLRs affect the development
of vitiligo, thus making them interesting targets for future research.
PMID- 26442099
TI - Aging and chronic administration of serotonin-selective reuptake inhibitor
citalopram upregulate Sirt4 gene expression in the preoptic area of male mice.
AB - Sexual dysfunction and cognitive deficits are markers of the aging process.
Mammalian sirtuins (SIRT), encoded by sirt 1-7 genes, are known as aging
molecules which are sensitive to serotonin (5-hydroxytryptamine, 5-HT). Whether
the 5-HT system regulates SIRT in the preoptic area (POA), which could affect
reproduction and cognition has not been examined. Therefore, this study was
designed to examine the effects of citalopram (CIT, 10 mg/kg for 4 weeks), a
potent selective-serotonin reuptake inhibitor and aging on SIRT expression in the
POA of male mice using real-time PCR and immunocytochemistry. Age-related
increases of sirt1, sirt4, sirt5, and sirt7 mRNA levels were observed in the POA
of 52 weeks old mice. Furthermore, 4 weeks of chronic CIT treatment started at 8
weeks of age also increased sirt2 and sirt4 mRNA expression in the POA. Moreover,
the number of SIRT4 immuno-reactive neurons increased with aging in the medial
septum area (12 weeks = 1.00 +/- 0.15 vs. 36 weeks = 1.68 +/- 0.14 vs. 52 weeks =
1.54 +/- 0.11, p < 0.05). In contrast, the number of sirt4-immunopositive cells
did not show a statistically significant change with CIT treatment, suggesting
that the increase in sirt4 mRNA levels may occur in cells in which sirt4 is
already being expressed. Taken together, these studies suggest that CIT treatment
and the process of aging utilize the serotonergic system to up-regulate SIRT4 in
the POA as a common pathway to deregulate social cognitive and reproductive
functions.
PMID- 26442101
TI - Molecular footprinting of skeletal tissues in the catshark Scyliorhinus canicula
and the clawed frog Xenopus tropicalis identifies conserved and derived features
of vertebrate calcification.
AB - Understanding the evolutionary emergence and subsequent diversification of the
vertebrate skeleton requires a comprehensive view of the diverse skeletal cell
types found in distinct developmental contexts, tissues, and species. To date,
our knowledge of the molecular nature of the shark calcified extracellular
matrix, and its relationships with osteichthyan skeletal tissues, remain scarce.
Here, based on specific combinations of expression patterns of the Col1a1,
Col1a2, and Col2a1 fibrillar collagen genes, we compare the molecular footprint
of endoskeletal elements from the chondrichthyan Scyliorhinus canicula and the
tetrapod Xenopus tropicalis. We find that, depending on the anatomical location,
Scyliorhinus skeletal calcification is associated to cell types expressing
different subsets of fibrillar collagen genes, such as high levels of Col1a1 and
Col1a2 in the neural arches, high levels of Col2a1 in the tesserae, or associated
to a drastic Col2a1 downregulation in the centrum. We detect low Col2a1 levels in
Xenopus osteoblasts, thereby revealing that the osteoblastic expression of this
gene was significantly reduced in the tetrapod lineage. Finally, we uncover a
striking parallel, from a molecular and histological perspective, between the
vertebral cartilage calcification of both species and discuss the evolutionary
origin of endochondral ossification.
PMID- 26442100
TI - Fine-tuning the ubiquitin code at DNA double-strand breaks: deubiquitinating
enzymes at work.
AB - Ubiquitination is a reversible protein modification broadly implicated in
cellular functions. Signaling processes mediated by ubiquitin (ub) are crucial
for the cellular response to DNA double-strand breaks (DSBs), one of the most
dangerous types of DNA lesions. In particular, the DSB response critically relies
on active ubiquitination by the RNF8 and RNF168 ub ligases at the chromatin,
which is essential for proper DSB signaling and repair. How this pathway is fine
tuned and what the functional consequences are of its deregulation for genome
integrity and tissue homeostasis are subject of intense investigation. One
important regulatory mechanism is by reversal of substrate ubiquitination through
the activity of specific deubiquitinating enzymes (DUBs), as supported by the
implication of a growing number of DUBs in DNA damage response processes. Here,
we discuss the current knowledge of how ub-mediated signaling at DSBs is
controlled by DUBs, with main focus on DUBs targeting histone H2A and on their
recent implication in stem cell biology and cancer.
PMID- 26442102
TI - From limbs to leaves: common themes in evolutionary diversification of organ
form.
AB - An open problem in biology is to derive general principles that capture how
morphogenesis evolved to generate diverse forms in different organisms. Here we
discuss recent work investigating the morphogenetic basis for digit loss in
vertebrate limbs and variation in form of marginal outgrowths of angiosperm
(flowering plant) leaves. Two pathways underlie digit loss in vertebrate limbs.
First, alterations to digit patterning arise through modification of expression
of the Patched 1 receptor, which senses the Sonic Hedgehog morphogen and limits
its mobility in the limb bud. Second, evolutionary changes to the degree of
programmed cell death between digits influence their development after their
initiation. Similarly, evolutionary modification of leaf margin outgrowths occurs
via two broad pathways. First, species-specific transcription factor expression
modulates outgrowth patterning dependent on regulated transport of the hormone
auxin. Second, species-specific expression of the newly discovered REDUCED
COMPLEXITY homeodomain transcription factor influences growth between individual
outgrowths after their initiation. These findings demonstrate that in both plants
and animals tinkering with either patterning or post-patterning processes can
cause morphological change. They also highlight the considerable flexibility of
morphological evolution and indicate that it may be possible to derive broad
principles that capture how morphogenesis evolved across complex eukaryotes.
PMID- 26442103
TI - A survey about methods dedicated to epistasis detection.
AB - During the past decade, findings of genome-wide association studies (GWAS)
improved our knowledge and understanding of disease genetics. To date, thousands
of SNPs have been associated with diseases and other complex traits. Statistical
analysis typically looks for association between a phenotype and a SNP taken
individually via single-locus tests. However, geneticists admit this is an
oversimplified approach to tackle the complexity of underlying biological
mechanisms. Interaction between SNPs, namely epistasis, must be considered.
Unfortunately, epistasis detection gives rise to analytic challenges since
analyzing every SNP combination is at present impractical at a genome-wide scale.
In this review, we will present the main strategies recently proposed to detect
epistatic interactions, along with their operating principle. Some of these
methods are exhaustive, such as multifactor dimensionality reduction, likelihood
ratio-based tests or receiver operating characteristic curve analysis; some are
non-exhaustive, such as machine learning techniques (random forests, Bayesian
networks) or combinatorial optimization approaches (ant colony optimization,
computational evolution system).
PMID- 26442104
TI - Establishing the pig as a large animal model for vaccine development against
human cancer.
AB - Immunotherapy has increased overall survival of metastatic cancer patients, and
cancer antigens are promising vaccine targets. To fulfill the promise,
appropriate tailoring of the vaccine formulations to mount in vivo cytotoxic T
cell (CTL) responses toward co-delivered cancer antigens is essential. Previous
development of therapeutic cancer vaccines has largely been based on studies in
mice, and the majority of these candidate vaccines failed to induce therapeutic
responses in the subsequent human clinical trials. Given that antigen dose and
vaccine volume in pigs are translatable to humans and the porcine immunome is
closer related to the human counterpart, we here introduce pigs as a
supplementary large animal model for human cancer vaccine development. IDO and
RhoC, both important in human cancer development and progression, were used as
vaccine targets and 12 pigs were immunized with overlapping 20mer peptides
spanning the entire porcine IDO and RhoC sequences formulated in CTL-inducing
adjuvants: CAF09, CASAC, Montanide ISA 51 VG, or PBS. Taking advantage of
recombinant swine MHC class I molecules (SLAs), the peptide-SLA complex stability
was measured for 198 IDO- or RhoC-derived 9-11mer peptides predicted to bind to
SLA-1(*)04:01, -1(*)07:02, -2(*)04:01, -2(*)05:02, and/or -3(*)04:01. This
identified 89 stable (t1/2 >= 0.5 h) peptide-SLA complexes. By IFN-gamma release
in PBMC cultures we monitored the vaccine-induced peptide-specific CTL responses,
and found responses to both IDO- and RhoC-derived peptides across all groups with
no adjuvant being superior. These findings support the further use of pigs as a
large animal model for vaccine development against human cancer.
PMID- 26442105
TI - Design, measurement and processing of region-specific DNA methylation assays: the
mass spectrometry-based method EpiTYPER.
AB - EpiTYPER(r) is a mass spectrometry-based bisulfite sequencing method that enables
region-specific DNA methylation analysis in a quantitative and high-throughput
fashion. The technology targets genomic regions of 100-600 base pairs and results
in the quantitative measurement of DNA methylation levels largely at single
nucleotide resolution. It is particularly suitable for larger scale efforts to
study candidate regions or to validate regions from genome-wide DNA methylation
studies. Here, we describe in detail how to design and perform EpiTYPER
measurements and preprocess the data, providing details for high quality
measurements not provided in the standard EpiTYPER protocol.
PMID- 26442107
TI - Quo vadis computational analysis of PPI data or why the future isn't here yet.
PMID- 26442106
TI - Exome sequencing of a colorectal cancer family reveals shared mutation pattern
and predisposition circuitry along tumor pathways.
AB - The molecular basis of cancer and cancer multiple phenotypes are not yet fully
understood. Next Generation Sequencing promises new insight into the role of
genetic interactions in shaping the complexity of cancer. Aiming to outline the
differences in mutation patterns between familial colorectal cancer cases and
controls we analyzed whole exomes of cancer tissues and control samples from an
extended colorectal cancer pedigree, providing one of the first data sets of
exome sequencing of cancer in an African population against a background of large
effective size typically with excess of variants. Tumors showed hMSH2 loss of
function SNV consistent with Lynch syndrome. Sets of genes harboring insertions
deletions in tumor tissues revealed, however, significant GO enrichment, a
feature that was not seen in control samples, suggesting that ordered insertions
deletions are central to tumorigenesis in this type of cancer. Network analysis
identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable
centrality, interacting specially with genes harboring non-synonymous SNVs thus
reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely
explanation to such mutation pattern is DNA/RNA editing, suggested here by
nucleotide transition-to-transversion ratio that significantly departed from
expected values (p-value 5e-6). NFKB1 also showed significant centrality along
with ELAVL1, raising the suspicion of viral etiology given the known interaction
between oncogenic viruses and these proteins.
PMID- 26442108
TI - Normal vs. Malignant hematopoiesis: the complexity of acute leukemia through
systems biology.
PMID- 26442109
TI - Efficacy of the porcine species in biomedical research.
AB - Since domestication, pigs have been used extensively in agriculture and kept as
companion animals. More recently they have been used in biomedical research,
given they share many physiological and anatomical similarities with humans.
Recent technological advances in assisted reproduction, somatic cell cloning,
stem cell culture, genome editing, and transgenesis now enable the creation of
unique porcine models of human diseases. Here, we highlight the potential
applications and advantages of using pigs, particularly minipigs, as
indispensable large animal models in fundamental and clinical research, including
the development of therapeutics for inherited and chronic disorders, and cancers.
PMID- 26442111
TI - Corrigendum: Historical factors that have shaped the evolution of tropical reef
fishes: a review of phylogenies, biogeography, and remaining questions.
AB - [This corrects the article on p. 394 in vol. 5, PMID: 25431581.].
PMID- 26442110
TI - Selection and validation of potato candidate genes for maturity corrected
resistance to Phytophthora infestans based on differential expression combined
with SNP association and linkage mapping.
AB - Late blight of potato (Solanum tuberosum L.) caused by the oomycete Phytophthora
infestans (Mont.) de Bary, is one of the most important bottlenecks of potato
production worldwide. Cultivars with high levels of durable, race unspecific,
quantitative resistance are part of a solution to this problem. However, breeding
for quantitative resistance is hampered by the correlation between resistance and
late plant maturity, which is an undesirable agricultural attribute. The
objectives of our research are (i) the identification of genes that condition
quantitative resistance to P. infestans not compromised by late plant maturity
and (ii) the discovery of diagnostic single nucleotide polymorphism (SNP) markers
to be used as molecular tools to increase efficiency and precision of resistance
breeding. Twenty two novel candidate genes were selected based on comparative
transcript profiling by SuperSAGE (serial analysis of gene expression) in groups
of plants with contrasting levels of maturity corrected resistance (MCR).
Reproducibility of differential expression was tested by quantitative real time
PCR and allele specific pyrosequencing in four new sets of genotype pools with
contrasting late blight resistance levels, at three infection time points and in
three independent infection experiments. Reproducibility of expression patterns
ranged from 28 to 97%. Association mapping in a panel of 184 tetraploid cultivars
identified SNPs in five candidate genes that were associated with MCR. These SNPs
can be used in marker-assisted resistance breeding. Linkage mapping in two half
sib families (n = 111) identified SNPs in three candidate genes that were linked
with MCR. The differentially expressed genes that showed association and/or
linkage with MCR putatively function in phytosterol synthesis, fatty acid
synthesis, asparagine synthesis, chlorophyll synthesis, cell wall modification,
and in the response to pathogen elicitors.
PMID- 26442112
TI - Mining protein interactomes to improve their reliability and support the
advancement of network medicine.
AB - High-throughput detection of protein interactions has had a major impact in our
understanding of the intricate molecular machinery underlying the living cell,
and has permitted the construction of very large protein interactomes. The
protein networks that are currently available are incomplete and a significant
percentage of their interactions are false positives. Fortunately, the structural
properties observed in good quality social or technological networks are also
present in biological systems. This has encouraged the development of tools, to
improve the reliability of protein networks and predict new interactions based
merely on the topological characteristics of their components. Since diseases are
rarely caused by the malfunction of a single protein, having a more complete and
reliable interactome is crucial in order to identify groups of inter-related
proteins involved in disease etiology. These system components can then be
targeted with minimal collateral damage. In this article, an important number of
network mining tools is reviewed, together with resources from which reliable
protein interactomes can be constructed. In addition to the review, a few
representative examples of how molecular and clinical data can be integrated to
deepen our understanding of pathogenesis are discussed.
PMID- 26442114
TI - Identification of single nucleotide polymorphism markers associated with
bacterial cold water disease resistance and spleen size in rainbow trout.
AB - Bacterial cold water disease (BCWD) is one of the frequent causes of elevated
mortality in salmonid aquaculture. Previously, we identified and validated
microsatellites on chromosome Omy19 associated with QTL (quantitative trait loci)
for BCWD resistance and spleen size in rainbow trout. Recently, SNPs (single
nucleotide polymorphism) have become the markers of choice for genetic analyses
in rainbow trout as they are highly abundant, cost-effective and are amenable for
high throughput genotyping. The objective of this study was to identify SNP
markers associated with BCWD resistance and spleen size using both genome-wide
association studies (GWAS) and linkage-based QTL mapping approaches. A total of
298 offspring from the two half-sib families used in our previous study to
validate the significant BCWD QTL on chromosome Omy19 were genotyped with RAD-seq
(restriction-site-associated DNA sequencing), and 7,849 informative SNPs were
identified. Based on GWAS, 18 SNPs associated with BCWD resistance and 20 SNPs
associated with spleen size were identified. Linkage-based QTL mapping revealed
three significant QTL for BCWD resistance. In addition to the previously
validated dam-derived QTL on chromosome Omy19, two significant BCWD QTL derived
from the sires were identified on chromosomes Omy8 and Omy25, respectively. A
sire-derived significant QTL for spleen size on chromosome Omy2 was detected. The
SNP markers reported in this study will facilitate fine mapping to identify
positional candidate genes for BCWD resistance in rainbow trout.
PMID- 26442113
TI - On the evolutionary relationship between chondrocytes and osteoblasts.
AB - Vertebrates are the only animals that produce bone, but the molecular genetic
basis for this evolutionary novelty remains obscure. Here, we synthesize
information from traditional evolutionary and modern molecular genetic studies in
order to generate a working hypothesis on the evolution of the gene regulatory
network (GRN) underlying bone formation. Since transcription factors are often
core components of GRNs (i.e., kernels), we focus our analyses on Sox9 and Runx2.
Our argument centers on three skeletal tissues that comprise the majority of the
vertebrate skeleton: immature cartilage, mature cartilage, and bone. Immature
cartilage is produced during early stages of cartilage differentiation and can
persist into adulthood, whereas mature cartilage undergoes additional stages of
differentiation, including hypertrophy and mineralization. Functionally,
histologically, and embryologically, these three skeletal tissues are very
similar, yet unique, suggesting that one might have evolved from another.
Traditional studies of the fossil record, comparative anatomy and embryology
demonstrate clearly that immature cartilage evolved before mature cartilage or
bone. Modern molecular approaches show that the GRNs regulating differentiation
of these three skeletal cell fates are similar, yet unique, just like the
functional and histological features of the tissues themselves. Intriguingly, the
Sox9 GRN driving cartilage formation appears to be dominant to the Runx2 GRN of
bone. Emphasizing an embryological and evolutionary transcriptomic view, we
hypothesize that the Runx2 GRN underlying bone formation was co-opted from mature
cartilage. We discuss how modern molecular genetic experiments, such as
comparative transcriptomics, can test this hypothesis directly, meanwhile
permitting levels of constraint and adaptation to be evaluated quantitatively.
Therefore, comparative transcriptomics may revolutionize understanding of not
only the clade-specific evolution of skeletal cells, but also the generation of
evolutionary novelties, providing a modern paradigm for the evolutionary process.
PMID- 26442115
TI - A new age in functional genomics using CRISPR/Cas9 in arrayed library screening.
AB - CRISPR technology has rapidly changed the face of biological research, such that
precise genome editing has now become routine for many labs within several years
of its initial development. What makes CRISPR/Cas9 so revolutionary is the
ability to target a protein (Cas9) to an exact genomic locus, through designing a
specific short complementary nucleotide sequence, that together with a common
scaffold sequence, constitute the guide RNA bridging the protein and the DNA.
Wild-type Cas9 cleaves both DNA strands at its target sequence, but this protein
can also be modified to exert many other functions. For instance, by attaching an
activation domain to catalytically inactive Cas9 and targeting a promoter region,
it is possible to stimulate the expression of a specific endogenous gene. In
principle, any genomic region can be targeted, and recent efforts have
successfully generated pooled guide RNA libraries for coding and regulatory
regions of human, mouse and Drosophila genomes with high coverage, thus
facilitating functional phenotypic screening. In this review, we will highlight
recent developments in the area of CRISPR-based functional genomics and discuss
potential future directions, with a special focus on mammalian cell systems and
arrayed library screening.
PMID- 26442117
TI - Past, present, and future of epigenetics applied to livestock breeding.
AB - This article reviews the concept of Lamarckian inheritance and the use of the
term epigenetics in the field of animal genetics. Epigenetics was first coined by
Conrad Hal Waddington (1905-1975), who derived the term from the Aristotelian
word epigenesis. There exists some controversy around the word epigenetics and
its broad definition. It includes any modification of the expression of genes due
to factors other than mutation in the DNA sequence. This involves DNA
methylation, post-translational modification of histones, but also linked to
regulation of gene expression by non-coding RNAs, genome instabilities or any
other force that could modify a phenotype. There is little evidence of the
existence of transgenerational epigenetic inheritance in mammals, which may
commonly be confounded with environmental forces acting simultaneously on an
individual, her developing fetus and the germ cell lines of the latter, although
it could have an important role in the cellular energetic status of cells.
Finally, we review some of the scarce literature on the use of epigenetics in
animal breeding programs.
PMID- 26442116
TI - Epigenetic marks: regulators of livestock phenotypes and conceivable sources of
missing variation in livestock improvement programs.
AB - Improvement in animal productivity has been achieved over the years through
careful breeding and selection programs. Today, variations in the genome are
gaining increasing importance in livestock improvement strategies. Genomic
information alone, however, explains only a part of the phenotypic variance in
traits. It is likely that a portion of the unaccounted variance is embedded in
the epigenome. The epigenome encompasses epigenetic marks such as DNA
methylation, histone tail modifications, chromatin remodeling, and other
molecules that can transmit epigenetic information such as non-coding RNA
species. Epigenetic factors respond to external or internal environmental cues
such as nutrition, pathogens, and climate, and have the ability to change gene
expression leading to emergence of specific phenotypes. Accumulating evidence
shows that epigenetic marks influence gene expression and phenotypic outcome in
livestock species. This review examines available evidence of the influence of
epigenetic marks on livestock (cattle, sheep, goat, and pig) traits and discusses
the potential for consideration of epigenetic markers in livestock improvement
programs. However, epigenetic research activities on farm animal species are
currently limited partly due to lack of recognition, funding and a global network
of researchers. Therefore, considerable less attention has been given to
epigenetic research in livestock species in comparison to extensive work in
humans and model organisms. Elucidating therefore the epigenetic determinants of
animal diseases and complex traits may represent one of the principal challenges
to use epigenetic markers for further improvement of animal productivity.
PMID- 26442118
TI - A Comparative Study Examining the Management of Bowen's Disease in the United
Kingdom and Australia.
AB - Background and Aim. The optimum management of Bowen's Disease (BD) is undefined.
A review of current practice is required to allow the development of best
practice guidelines. Methods. All BD cases, diagnosed in one UK centre and one
Australian centre over a year (1 July 2012-30 June 2013), were analysed
retrospectively. Patients with BD were identified from histopathology reports and
their medical records were analysed to collect demographic data, site of lesion,
and treatment used. Results. The treatment of 155 lesions from the UK centre and
151 lesions from the Australian centre was analysed. At both centres BD was most
frequently observed on the face: UK had 70 (45%) lesions and Australia had 83
(55%) lesions (P = 0.08). The greatest number of lesions was managed by the
plastic surgery department in the UK centre, 72 (46%), and the dermatology
department in the Australian centre, 121 (80%). The most common therapy was
surgical excision at both centres. Conclusions. In both UK and Australia, BD
arises on sun-exposed sites and was most commonly treated with surgical excision
despite a lack of robust evidence-based guidelines.
PMID- 26442120
TI - The Age-Specific Association of Waist Circumference and Risk of Chronic Kidney
Disease in Patients with Type 2 Diabetes Mellitus in Shandong, China.
AB - Objective. To examine the association of three most common obesity measures
including body mass index (BMI), waist circumference (WC), and waist-to-hip ratio
(WHR) with chronic kidney disease (CKD) risk in patients with type 2 diabetes
mellitus (T2D). Design. Cross-sectional evaluation of the effect of
anthropometric measures on CKD risk. Setting. Outpatient Department. Subjects.
T2D patients who were treated between October 2012 and May 2013. Intervention.
None. Main Outcome Measure. CKD risk. Results. On average, the patients had a
mean age of 60.2 years, and 40% were males. CKD was present in 46% of all the
patients. In multivariate logistic regression using the imputed data, higher WC
was associated with greater odds of CKD (OR = 1.019, 95% CI = 1.002-1.006, P =
0.030), but not BMI and WHR. Interestingly, we found that patients with very
small WC seemed to have greater odds of CKD. We observed age-specific effect of
WC such that the effect of WC on CKD risk is significant only in middle-aged T2D
patients. Conclusion. Our study provides evidence for the association of WC with
CKD in Chinese patients with T2D. T2D patients, especially middle-aged T2D
patients, should reduce their WC to decrease CKD risk.
PMID- 26442119
TI - Therapeutic Potential of Dietary Phenolic Acids.
AB - Although modern lifestyle has eased the quality of human life, this lifestyle's
related patterns have imparted negative effects on health to acquire multiple
diseases. Many synthetic drugs are invented during the last millennium but most
if not all of them possess several side effects and proved to be costly.
Convincing evidences have established the premise that the phytotherapeutic
potential of natural compounds and need of search for novel drugs from natural
sources are of high priority. Phenolic acids (PAs) are a class of secondary
metabolites spread throughout the plant kingdom and generally involved in
plethora of cellular processes involved in plant growth and reproduction and also
produced as defense mechanism to sustain various environmental stresses.
Extensive research on PAs strongly suggests that consumption of these compounds
hold promise to offer protection against various ailments in humans. This paper
focuses on the naturally derived PAs and summarizes the action mechanisms of
these compounds during disease conditions. Based on the available information in
the literature, it is suggested that use of PAs as drugs is very promising;
however more research and clinical trials are necessary before these bioactive
molecules can be made for treatment. Finally this review provides greater
awareness of the promise that natural PAs hold for use in the disease prevention
and therapy.
PMID- 26442121
TI - The Intervention Effects of Acupuncture on Fatigue Induced by Exhaustive Physical
Exercises: A Metabolomics Investigation.
AB - In this study, the antifatigue effects of acupuncture had been investigated at
the metabolic level on the young male athletes with exhaustive physical
exercises. After a series of exhaustive physical exercises and a short-term rest,
the athletes either were treated with needling acupuncture on selected acupoints
(TA group) or enjoyed an extended rest (TR group). NMR-based metabolomics
analysis was then applied to depict the metabolic profiles of urine samples,
which were collected from the athletes at three time points including the time
before exercises, the time before and after the treatment of acupuncture, or
taking the extended rest. The results from multivariate statistical analysis
indicated that the recoveries of disturbed metabolites in the athletes treated
with acupuncture were significantly faster than in those only taking rest. After
the treatment with acupuncture, the levels of distinguished metabolites, 2
hydroxybutyrate, 3-hydroxyisovalerate, lactate, pyruvate, citrate,
dimethylglycine, choline, glycine, hippurate, and hypoxanthine were recovered at
an accelerated speed in the TA group in comparison with the TR group. The above
mentioned results indicated that the acupuncture treatment ameliorated fatigue by
backregulating the perturbed energy metabolism, choline metabolism, and
attenuating the ROS-induced stress at an accelerated speed, which demonstrated
that acupuncture could serve as an alternative fatigue-relieving approach.
PMID- 26442122
TI - The Effect of Monochromatic Infrared Photo Energy on the Irritability of
Myofascial Trigger Spot of Rabbit Skeletal Muscle.
AB - Objective. To determine whether the vasodilatation effect of monochromatic
infrared photo energy (MIRE) had the potential for the treatment of myofascial
trigger spot (MTrS) in rabbits. Design. A randomized-controlled animal study.
Subjects. Twelve adult New Zealand rabbits. Methods. For each rabbit, a MTrS
(equivalent to a myofascial trigger point in humans) in one side of the biceps
femoris muscle was randomly selected for MIRE treatment (experimental side),
while another MTrS in the other side (control side) received a sham treatment.
The intervention consisted of a daily 40 minutes treatment, three times per week
for 2 weeks. The prevalence of endplate noise (EPN) loci in the MTrS was assessed
before, immediately after, and one week after the completion of the 2-week
treatment. Results. MIRE could suppress the prevalence of EPN in the MTrS. The
degree of reduction in EPN prevalence in the MTrS between the experimental side
and the control side was significantly different immediately after MIRE
treatment, but not significantly different one week after MIRE treatment.
Conclusion. Our study suggests that MIRE may be a useful therapeutic option for
the management of the myofascial trigger point in humans.
PMID- 26442124
TI - Use of Tranexamic Acid (TXA) on reducing blood loss during scoliosis surgery in
Chinese adolescents.
AB - BACKGROUND: Many reports had been received on the application of antifibrinolytic
medications on spinal corrective surgery and the surgical outcome evaluations of
its efficacy on reducing blood loss. This study aimed to assess the efficacy of
tranexamic acid (TXA) in reducing operative blood loss during posterior spinal
fusion for the treatment of severe adolescent idiopathic scoliosis (AIS).
METHODS: A retrospective cohort study was carried out on 90 (TXA = 55, Control =
35) AIS girls undergoing posterior spinal surgery. Patients in TXA group used TXA
as an antifibrinolytic agent to reduce blood loss, while control group did not.
Blood loss, haemoglobin change and amount of blood transfused was estimated from
intraoperative measurement by anaesthesiologists. Demographics were compared
using Student's T-test or Chi-square test where appropriate. Linear regression
modelling was carried out between the use of TXA and total blood loss with
controlling of confounding factors. RESULTS: Mean age and mean maximum major
curve were 15.2 and 73 degrees , and 15.3 and 63 degrees in TXA and control
groups respectively. TXA group showed significantly less intra-operative blood
loss than the control group from intraoperative measurement (1.8 L vs. 3.9 L, p <
0.01) and volume of cell saver blood transfused back to patients (0.6 L vs. 1.7
L, p < 0.01). TXA group also showed significantly shorter total time taken for
surgery (437 min vs. 502 min, p < 0.01), and total blood loss per surgical
segment level (0.1 L vs. 0.3 L, p < 0.01). Regression models showed that the use
of TXA decreased total blood loss by 794.3 ml after adjusting for maximum major
curve, age, number of segments fused, bone graft, clotting capability, and
infusion of coagulation factors. CONCLUSIONS: Patients undergoing posterior
spinal corrective surgery with the use of TXA showed much reduced total blood
loss, reduced use of transfused blood, much less cell saver blood transfused back
to the patient. The total blood loss was decreased by after using TXA after
controlling for maximum major curve, age, surgical parameters, clotting
capability, and infusion of coagulation factors.
PMID- 26442125
TI - Role of Microstructure in the Electron-Hole Interaction of Hybrid Lead-Halide
Perovskites.
AB - Solar cells based on hybrid inorganic-organic halide perovskites have
demonstrated high power conversion efficiencies in a range of architectures. The
existence and stability of bound electron-hole pairs in these materials, and
their role in the exceptional performance of optoelectronic devices, remains a
controversial issue. Here we demonstrate, through a combination of optical
spectroscopy and multiscale modeling as a function of the degree of
polycrystallinity and temperature, that the electron-hole interaction is
sensitive to the microstructure of the material. The long-range order is
disrupted by polycrystalline disorder and the variations in electrostatic
potential found for smaller crystals suppress exciton formation, while larger
crystals of the same composition demonstrate an unambiguous excitonic state. We
conclude that fabrication procedures and morphology strongly influence perovskite
behaviour, with both free carrier and excitonic regimes possible, with strong
implications for optoelectronic devices.
PMID- 26442123
TI - Optimizing Weight for Maternal and Infant Health - Tenable, or Too Late?
AB - Obesity in pregnancy is the leading cause of maternal and fetal morbidity, and
gestational weight gain (GWG) is one modifiable risk factor that improves
pregnancy outcomes. Most pregnant women gain more than the 2009 Institute of
Medicine recommendations, particularly overweight and obese women. GWG even less
than the 2009 IOM guidelines in obese women may improve pregnancy outcomes and
reduce large-for-gestational-age (LGA) infants, an independent risk factor for
childhood obesity, without increasing small-for-gestational-age (SGA) infants.
Unfortunately, despite the fact that over 50 interventional trials designed to
decrease excess GWG have been conducted, these interventions have been only
modestly effective, and interventions designed to facilitate weight postpartum
weight loss have also been disappointing. Successful interventions are of
paramount importance not only to improve pregnancy outcomes but also for the
future metabolic health of the mother and her infant, and may be key in
attenuating the trans-generational risk on childhood obesity.
PMID- 26442126
TI - The Temporal Dynamics of Childhood Economic Deprivation and Children's
Achievement.
AB - Economic deprivation during childhood adversely affects achievement in
adolescence and early adulthood. Economically disadvantaged children tend to
achieve less than their more advantaged peers on a variety of measures of
educational and socioeconomic achievement. Researchers recognize that what
matters for achievement is not merely exposure to economic deprivation during
childhood but also the temporal dynamics of deprivation. Recent studies have
found that the effects of childhood economic disadvantage on achievement depend
on the timing of deprivation (early childhood versus middle or late childhood),
the sequencing of deprivation (whether family income is rising or falling), and
the overall duration of exposure to deprivation. In this article, I describe
conceptual and methodological advances in understanding the temporal dynamics of
childhood economic disadvantage, and address the implications of these
improvements for our knowledge of how deprivation affects children's achievement.
PMID- 26442127
TI - The predictive role of NLR and PLR for solid non-AIDS defining cancer incidence
in HIV-infected subjects: a MASTER cohort study.
AB - BACKGROUND: The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte
ratio (PLR), two low cost, routinely available inflammatory indices, have been
found to be associated with risk of death in patients with solid cancer, in both
general population and HIV-positive subjects. However, no study investigated the
role of NLR and PLR as predictive of cancer incidence so far. METHODS: The aim of
our study was to assess the association of PLR and NLR with risk of developing
solid non-AIDS defining cancer (NADC) in HIV-infected subjects. We conducted a
multicenter Italian cohort study from 2000 to 2012 including HIV-infected
subjects naive at antiretroviral treatment at enrollment. The associations of NLR
and PLR with NADC incidence were evaluated by univariate and multivariate
analyses using both time independent and time dependent Cox proportional hazard
models. RESULTS: Thirteen thousand five hundred fifty-nine patients (73.3 %
males) with a mean age of 36.0 years (SD 10.0) were included. The median (inter
quartile range) of NLR and PLR at baseline were 1.47 (1.03-2.17) and 109.9 (79.6
155.3), respectively. During a median follow-up of 3.9 years, 337 subjects had a
first diagnosis of solid NADC. The crude and age- and gender-standardized
incidence rates were 3.57 and 3.91 per 1000 person-years, respectively. No
statistically significant association was found between NLR and PLR and NADC
incidence, using multivariate models, including also time-dependent Cox models
with a cubic-spline for NLR and PLR. CONCLUSION: This study does not sustain the
hypothesis that NRL and PLR may be useful for predicting the risk of cancer in
HIV positive subjects.
PMID- 26442128
TI - Physical activity of elderly patients with rheumatoid arthritis and healthy
individuals: an actigraphy study.
AB - BACKGROUND: Most people with rheumatoid arthritis (RA) are physically inactive.
An accelerometer worn on the waist has been used to evaluate physical activity in
people with chronic conditions. It is useful for evaluating moderate to vigorous
activity, although it tends to underestimate light or mild activities such as
housework or family duties. An accelerometer worn on the wrist (i.e., actigraph)
has recently been used to capture daily physical activity in inactive
individuals. The purposes of this study were to investigate physical activity
measured by an actigraph in patients with RA and in healthy individuals and to
investigate the association between actigraphic data and self-reported physical
function. METHODS: The subjects were 20 RA patients and 20 healthy individuals.
All participants wore an actigraph on their wrist for 6-7 consecutive days. They
also completed the Health Assessment Questionnaire disability index (HAQ-DI) and
the Medical Outcomes Study (MOS) 36-item short form health survey (SF-36). We
extracted three parameters from the actigraphic data: mean activity count (MAC),
peak activity count (PAC), and low activity ratio (LAR). These three parameters
were compared between the RA patients and healthy individuals and with the self
reported questionnaires. RESULTS: The MAC was significantly lower and the LAR was
significantly higher in RA patients than in healthy individuals. The PAC was not
different between the two groups. The LAR was negatively correlated with the MAC
for the RA patients and for the healthy individuals. The decrease ratio of the
LAR with the increase of the MAC for the RA patients was twice that of the
healthy participants. In the RA patients, the LAR was significantly and
moderately correlated with the HAQ-DI score and two dimensions of the SF-36
(i.e., "physical functioning" and "bodily pain"). CONCLUSION: Investigation of
the proportion of low activity count using an actigraph may be useful to identify
characteristics of the physical function in RA patients.
PMID- 26442129
TI - Health service resilience in Yobe state, Nigeria in the context of the Boko Haram
insurgency: a systems dynamics analysis using group model building.
AB - BACKGROUND: Yobe State has faced severe disruption of its health service as a
result of the Boko Haram insurgency. A systems dynamics analysis was conducted to
identify key pathways of threat to provision and emerging pathways of response
and adaptation. METHODS: Structured interviews were conducted with 39
stakeholders from three local government areas selected to represent the
diversity of conflict experience across the state: Damaturu, Fune and Nguru, and
with four officers of the PRRINN-MNCH program providing technical assistance for
primary care development in the state. A group model building session was
convened with 11 senior stakeholders, which used participatory scripts to review
thematic analysis of interviews and develop a preliminary systems model linking
identified variables. RESULTS: Population migration and transport restrictions
have substantially impacted access to health provision. The human resource for
health capability of the state has been severely diminished through the outward
migration of (especially non-indigenous) health workers and the suspension of
programmes providing external technical assistance. The political will of the
Yobe State government to strengthen health provision - through lifting a
moratorium on recruitment and providing incentives for retention and support of
staff - has supported a recovery of health systems functioning. Policies of free
drug provision and decentralized drug supply appear to have been protective of
the operation of the health system. Community resources and cohesion have been
significant assets in combatting the impacts of the insurgency on service
utilization and quality. Staff commitment and motivation - particularly amongst
staff indigenous to the state - has protected health care quality and enabled
flexibility of human resource deployment. CONCLUSIONS: A systems analysis using
participatory group model building provided a mechanism to identify key pathways
of threat and adaptation with regard to health service functioning. Generalizable
systems characteristics supportive of resilience are suggested, and linked to
wider discussion of the role of factors such as diversity, self-regulation and
integration.
PMID- 26442130
TI - The influence of maternal health education on the place of delivery in conflict
settings of Darfur, Sudan.
AB - BACKGROUND: Armed conflict and socio-demographic characteristics of internally
displaced persons (IDPs) are very important factors that influence the provision
of reproductive health (RH) in humanitarian settings. Maternal health education
plays a crucial role to overcome the barriers of RH care, reduce home births
conducted by traditional birth attendants (TBAs), and improve increasing births
in a health facility. The objectives of this study were to (1) determine the
association between the place of delivery and home visits for maternal health
education and (2) describe the socio-demographic characteristics of women who
gave birth during the last two years. METHODS: A cross-sectional study among
married women aged (15-49 years old) in IDP camps. All women were subjected to
intensive maternal health education at their homes for 3 years prior to the
survey. A sample of 640 women who gave birth during the last two years was
randomly selected. RESULTS: Among all women investigated, 36.9 % (95 % CI: 33.1,
40.8) reported a home-based delivery, while 63.1 % (95 % CI: 59.2, 66.9) reported
a facility-based delivery. Receiving visits for maternal health education at home
was associated with an estimated 43.0 % reduction in odds of giving birth at
home, compared to not receiving home visits (adjusted odds ratio [ aOR] 0.57; 95
% CI: 0.35, 0.93). The level of women's education and camp of residence were
important predictors for home birth. CONCLUSION: Maternal health education at
home was associated with a reduction in home-based delivery performed by TBAs in
the conflict-affected setting of Darfur. Our study proposes that when facility
based delivery is made available in camp's clinics, and the targeted women
educated at home to refrain from home-based delivery, they will choose to undergo
facility-based delivery.
PMID- 26442133
TI - NSAUA & QUA Joint Oncology Meeting.
PMID- 26442132
TI - Northeastern Section of the American Urological Association 67th Annual Meeting,
Quebec City, QC Scientific Program View Abstracts at NSAUA.org.
PMID- 26442131
TI - Mental Health Service Use in Schools and Non-School-Based Outpatient Settings:
Comparing Predictors of Service Use.
AB - Researchers have consistently documented a gap between the large number of US
youth meeting criteria for a mental health disorder with significant associated
impairment, and the comparatively few youth receiving services. School-based
mental health care may address the need-services gap by offering services more
equitably to youth in need, irrespective of family economic resources,
availability of transportation, and other factors that can impede access to
community clinics. However, diagnoses alone do not fully capture the severity of
an individual's mental health status and need for services. Studying service use
only in relation to diagnoses may restrict our understanding of the degree to
which service use is reflective of service need, and inhibit our ability to
compare school and non-school-based outpatient settings on their responsiveness
to service need. The present study evaluated predictors of mental health service
use in school- and community-based settings for youth who had had an active case
in one of two public sectors of care, comparing empirically-derived dimensional
measurements of youth mental health service need and impairment ratings against
non-need variables (e.g., ethnicity, income). Three dimensions of youth mental
health service need were identified. Mental health service need and non-need
variables each played a significant predictive role. Parent-rated impairment was
the strongest need-based predictor of service use across settings. The impact of
non-need variables varied by service setting, with parental income having a
particularly noticeable effect on school-based services. Across time, preceding
service use and impairment each significantly predicted future service use.
PMID- 26442134
TI - Developing Your Evaluation Plans: A Critical Component of Public Health Program
Infrastructure.
AB - A program's infrastructure is often cited as critical to public health success.
The Component Model of Infrastructure (CMI) identifies evaluation as essential
under the core component of engaged data. An evaluation plan is a written
document that describes how to monitor and evaluate a program, as well as how to
use evaluation results for program improvement and decision making. The
evaluation plan clarifies how to describe what the program did, how it worked,
and why outcomes matter. We use the Centers for Disease Control and Prevention's
(CDC) "Framework for Program Evaluation in Public Health" as a guide for
developing an evaluation plan. Just as using a roadmap facilitates progress on a
long journey, a well-written evaluation plan can clarify the direction your
evaluation takes and facilitate achievement of the evaluation's objectives.
PMID- 26442135
TI - Comparison of normalization methods for differential gene expression analysis in
RNA-Seq experiments: A matter of relative size of studied transcriptomes.
AB - In recent years, RNA-Seq technologies became a powerful tool for transcriptome
studies. However, computational methods dedicated to the analysis of high
throughput sequencing data are yet to be standardized. In particular, it is known
that the choice of a normalization procedure leads to a great variability in
results of differential gene expression analysis. The present study compares the
most widespread normalization procedures and proposes a novel one aiming at
removing an inherent bias of studied transcriptomes related to their relative
size. Comparisons of the normalization procedures are performed on real and
simulated data sets. Real RNA-Seq data sets analyses, performed with all the
different normalization methods, show that only 50% of significantly
differentially expressed genes are common. This result highlights the influence
of the normalization step on the differential expression analysis. Real and
simulated data sets analyses give similar results showing 3 different groups of
procedures having the same behavior. The group including the novel method named
"Median Ratio Normalization" (MRN) gives the lower number of false discoveries.
Within this group the MRN method is less sensitive to the modification of
parameters related to the relative size of transcriptomes such as the number of
down- and upregulated genes and the gene expression levels. The newly proposed
MRN method efficiently deals with intrinsic bias resulting from relative size of
studied transcriptomes. Validation with real and simulated data sets confirmed
that MRN is more consistent and robust than existing methods.
PMID- 26442136
TI - Complete genome sequence of Geobacillus thermoglucosidasius C56-YS93, a novel
biomass degrader isolated from obsidian hot spring in Yellowstone National Park.
AB - Geobacillus thermoglucosidasius C56-YS93 was one of several thermophilic
organisms isolated from Obsidian Hot Spring, Yellowstone National Park, Montana,
USA under permit from the National Park Service. Comparison of 16 S rRNA
sequences confirmed the classification of the strain as a G. thermoglucosidasius
species. The genome was sequenced, assembled, and annotated by the DOE Joint
Genome Institute and deposited at the NCBI in December 2011 (CP002835). The
genome of G. thermoglucosidasius C56-YS93 consists of one circular chromosome of
3,893,306 bp and two circular plasmids of 80,849 and 19,638 bp and an average G +
C content of 43.93 %. G. thermoglucosidasius C56-YS93 possesses a xylan
degradation cluster not found in the other G. thermoglucosidasius sequenced
strains. This cluster appears to be related to the xylan degradation cluster
found in G. stearothermophilus. G. thermoglucosidasius C56-YS93 possesses two
plasmids not found in the other two strains. One plasmid contains a novel gene
cluster coding for proteins involved in proline degradation and metabolism, the
other contains a collection of mostly hypothetical proteins.
PMID- 26442137
TI - Magnetic targeting of microbubbles against physiologically relevant flow
conditions.
AB - The localization of microbubbles to a treatment site has been shown to be
essential to their effectiveness in therapeutic applications such as targeted
drug delivery and gene therapy. A variety of different strategies for achieving
localization has been investigated, including biochemical targeting, acoustic
radiation force, and the incorporation of superparamagnetic nanoparticles into
microbubbles to enable their manipulation using an externally applied magnetic
field. The third of these strategies has the advantage of concentrating
microbubbles in a target region without exposing them to ultrasound, and can be
used in conjunction with biochemical targeting to achieve greater specificity.
Magnetic microbubbles have been shown to be effective for therapeutic delivery in
vitro and in vivo. Whether this technique can be successfully applied in humans
however remains an open question. The aim of this study was to determine the
range of flow conditions under which targeting could be achieved. In vitro
results indicate that magnetic microbubbles can be retained using clinically
acceptable magnetic fields, for both the high shear rates (approx. 10(4) s(-1))
found in human arterioles and capillaries, and the high flow rates (approx. 3.5
ml s(-1)) of human arteries. The potential for human in vivo microbubble
retention was further demonstrated using a perfused porcine liver model.
PMID- 26442138
TI - Cavitation inception from bubble nuclei.
AB - The tensile strength of ordinary water such as tap water or seawater is typically
well below 1 bar. It is governed by cavitation nuclei in the water, not by the
tensile strength of the water itself, which is extremely high. Different models
of the nuclei have been suggested over the years, and experimental investigations
of bubbles and cavitation inception have been presented. These results suggest
that cavitation nuclei in equilibrium are gaseous voids in the water, stabilized
by a skin which allows diffusion balance between gas inside the void and gas in
solution in the surrounding liquid. The cavitation nuclei may be free gas bubbles
in the bulk of water, or interfacial gaseous voids located on the surface of
particles in the water, or on bounding walls. The tensile strength of these
nuclei depends not only on the water quality but also on the pressure-time
history of the water. A recent model and associated experiments throw new light
on the effects of transient pressures on the tensile strength of water, which may
be notably reduced or increased by such pressure changes.
PMID- 26442139
TI - Towards numerical prediction of cavitation erosion.
AB - This paper is intended to provide a potential basis for a numerical prediction of
cavitation erosion damage. The proposed method can be divided into two steps. The
first step consists in determining the loading conditions due to cavitation
bubble collapses. It is shown that individual pits observed on highly polished
metallic samples exposed to cavitation for a relatively small time can be
considered as the signature of bubble collapse. By combining pitting tests with
an inverse finite-element modelling (FEM) of the material response to a
representative impact load, loading conditions can be derived for each individual
bubble collapse in terms of stress amplitude (in gigapascals) and radial extent
(in micrometres). This step requires characterizing as accurately as possible the
properties of the material exposed to cavitation. This characterization should
include the effect of strain rate, which is known to be high in cavitation
erosion (typically of the order of several thousands s(-1)). Nanoindentation
techniques as well as compressive tests at high strain rate using, for example, a
split Hopkinson pressure bar test system may be used. The second step consists in
developing an FEM approach to simulate the material response to the repetitive
impact loads determined in step 1. This includes a detailed analysis of the
hardening process (isotropic versus kinematic) in order to properly account for
fatigue as well as the development of a suitable model of material damage and
failure to account for mass loss. Although the whole method is not yet fully
operational, promising results are presented that show that such a numerical
method might be, in the long term, an alternative to correlative techniques used
so far for cavitation erosion prediction.
PMID- 26442140
TI - Modelling cavitation erosion using fluid-material interaction simulations.
AB - Material deformation and pitting from cavitation bubble collapse is investigated
using fluid and material dynamics and their interaction. In the fluid, a novel
hybrid approach, which links a boundary element method and a compressible finite
difference method, is used to capture non-spherical bubble dynamics and resulting
liquid pressures efficiently and accurately. The bubble dynamics is intimately
coupled with a finite-element structure model to enable fluid/structure
interaction simulations. Bubble collapse loads the material with high impulsive
pressures, which result from shock waves and bubble re-entrant jet direct impact
on the material surface. The shock wave loading can be from the re-entrant jet
impact on the opposite side of the bubble, the fast primary collapse of the
bubble, and/or the collapse of the remaining bubble ring. This produces high
stress waves, which propagate inside the material, cause deformation, and
eventually failure. A permanent deformation or pit is formed when the local
equivalent stresses exceed the material yield stress. The pressure loading
depends on bubble dynamics parameters such as the size of the bubble at its
maximum volume, the bubble standoff distance from the material wall and the
pressure driving the bubble collapse. The effects of standoff and material type
on the pressure loading and resulting pit formation are highlighted and the
effects of bubble interaction on pressure loading and material deformation are
preliminarily discussed.
PMID- 26442141
TI - Cavitation and bubble dynamics: the Kelvin impulse and its applications.
AB - Cavitation and bubble dynamics have a wide range of practical applications in a
range of disciplines, including hydraulic, mechanical and naval engineering, oil
exploration, clinical medicine and sonochemistry. However, this paper focuses on
how a fundamental concept, the Kelvin impulse, can provide practical insights
into engineering and industrial design problems. The pathway is provided through
physical insight, idealized experiments and enhancing the accuracy and
interpretation of the computation. In 1966, Benjamin and Ellis made a number of
important statements relating to the use of the Kelvin impulse in cavitation and
bubble dynamics, one of these being 'One should always reason in terms of the
Kelvin impulse, not in terms of the fluid momentum...'. We revisit part of this
paper, developing the Kelvin impulse from first principles, using it, not only as
a check on advanced computations (for which it was first used!), but also to
provide greater physical insights into cavitation bubble dynamics near boundaries
(rigid, potential free surface, two-fluid interface, flexible surface and
axisymmetric stagnation point flow) and to provide predictions on different types
of bubble collapse behaviour, later compared against experiments. The paper
concludes with two recent studies involving (i) the direction of the jet
formation in a cavitation bubble close to a rigid boundary in the presence of
high-intensity ultrasound propagated parallel to the surface and (ii) the study
of a 'paradigm bubble model' for the collapse of a translating spherical bubble,
sometimes leading to a constant velocity high-speed jet, known as the Longuet
Higgins jet.
PMID- 26442142
TI - Cell mechanics in biomedical cavitation.
AB - Studies on the deformation behaviours of cellular entities, such as coated
microbubbles and liposomes subject to a cavitation flow, become increasingly
important for the advancement of ultrasonic imaging and drug delivery. Numerical
simulations for bubble dynamics of ultrasound contrast agents based on the
boundary integral method are presented in this work. The effects of the
encapsulating shell are estimated by adapting Hoff's model used for thin-shell
contrast agents. The viscosity effects are estimated by including the normal
viscous stress in the boundary condition. In parallel, mechanical models of cell
membranes and liposomes as well as state-of-the-art techniques for quantitative
measurement of viscoelasticity for a single cell or coated microbubbles are
reviewed. The future developments regarding modelling and measurement of the
material properties of the cellular entities for cutting-edge biomedical
applications are also discussed.
PMID- 26442143
TI - Bubbles with shock waves and ultrasound: a review.
AB - The study of the interaction of bubbles with shock waves and ultrasound is
sometimes termed 'acoustic cavitation'. It is of importance in many biomedical
applications where sound waves are applied. The use of shock waves and ultrasound
in medical treatments is appealing because of their non-invasiveness. In this
review, we present a variety of acoustics-bubble interactions, with a focus on
shock wave-bubble interaction and bubble cloud phenomena. The dynamics of a
single spherically oscillating bubble is rather well understood. However, when
there is a nearby surface, the bubble often collapses non-spherically with a high
speed jet. The direction of the jet depends on the 'resistance' of the boundary:
the bubble jets towards a rigid boundary, splits up near an elastic boundary, and
jets away from a free surface. The presence of a shock wave complicates the
bubble dynamics further. We shall discuss both experimental studies using high
speed photography and numerical simulations involving shock wave-bubble
interaction. In biomedical applications, instead of a single bubble, often clouds
of bubbles appear (consisting of many individual bubbles). The dynamics of such a
bubble cloud is even more complex. We shall show some of the phenomena observed
in a high-intensity focused ultrasound (HIFU) field. The nonlinear nature of the
sound field and the complex inter-bubble interaction in a cloud present
challenges to a comprehensive understanding of the physics of the bubble cloud in
HIFU. We conclude the article with some comments on the challenges ahead.
PMID- 26442144
TI - Tiny bubbles challenge giant turbines: Three Gorges puzzle.
AB - Since the birth of the first prototype of the modern reaction turbine, cavitation
as conjectured by Euler in 1754 always presents as a challenge. Following his
theory, the evolution of modern reaction (Francis and Kaplan) turbines has been
completed by adding the final piece of the element 'draft-tube' that enables
turbines to explore water energy at efficiencies of almost 100%. However, during
the last two and a half centuries, with increasing unit capacity and specific
speed, the problem of cavitation has been manifested and complicated by the draft
tube surges rather than being solved. Particularly, during the last 20 years, the
fierce competition in the international market for extremely large turbines with
compact design has encouraged the development of giant Francis turbines of 700
1000 MW. The first group (24 units) of such giant turbines of 700 MW each was
installed in the Three Gorges project. Immediately after commission, a strange
erosion phenomenon appeared on the guide vane of the machines that has puzzled
professionals. From a multi-disciplinary analysis, this Three Gorges puzzle could
reflect an unknown type of cavitation inception presumably triggered by
turbulence production from the boundary-layer streak transitional process. It
thus presents a fresh challenge not only to this old turbine industry, but also
to the fundamental sciences.
PMID- 26442145
TI - Cavitation in medicine.
AB - We generally think of bubbles as benign and harmless and yet they can manifest
the most remarkable range of physical effects. Some of those effects are the
stuff of our everyday experience as in the tinkling of a brook or the sounds of
breaking waves at the beach. But even these mundane effects are examples of the
ability of bubbles to gather, focus and radiate energy (acoustic energy in the
above examples). In other contexts that focusing of energy can lead to serious
technological problems as when cavitation bubbles eat great holes through ships'
propeller blades or cause a threat to the integrity of the spillways at the
Hoover Dam. In liquid-propelled rocket engines, bubbles pose a danger to the
stability of the propulsion system, and in artificial heart valves they can cause
serious damage to the red blood cells. In perhaps the most extraordinary example
of energy focusing, collapsing cavitation bubbles can emit not only sound, but
also light with black body radiation temperatures equal to that of the sun
(Brennen 1995 Cavitation and bubble dynamics). But, harnessed carefully, this
almost unique ability to focus energy can also be put to remarkably constructive
use. Cavitation bubbles are now used in a remarkable range of surgical and
medical procedures, for example to emulsify tissue (most commonly in cataract
surgery or in lithotripsy procedures for the reduction of kidney and gall stones)
or to manipulate the DNA in individual cells. By creating cavitation bubbles non
invasively thereby depositing and focusing energy non-intrusively, one can
generate minute incisions or target cancer cells. This paper will begin by
briefly reviewing the history of cavitation phenomena and will end with a vision
of the new horizons for the amazing cavitation bubble.
PMID- 26442146
TI - The speed of sound in a gas-vapour bubbly liquid.
AB - In addition to the vapour of the liquid, bubbles in cavitating flows usually
contain also a certain amount of permanent gas that diffuses out of the liquid as
they grow. This paper presents a simplified linear model for the propagation of
monochromatic pressure waves in a bubbly liquid with these characteristics. Phase
change effects are included in detail, while the gas is assumed to follow a
polytropic law. It is shown that even a small amount of permanent gas can have a
major effect on the behaviour of the system. Particular attention is paid to the
low-frequency range, which is of special concern in flow cavitation. Numerical
results for water and liquid oxygen illustrate the implications of the model.
PMID- 26442147
TI - The singing vortex.
AB - Marine propellers display several forms of cavitation. Of these, propeller-tip
vortex cavitation is one of the important factors in propeller design. The
dynamic behaviour of the tip vortex is responsible for hull vibration and noise.
Thus, cavitation in the vortices trailing from tips of propeller blades has been
studied extensively. Under certain circumstances cavitating vortices have been
observed to have wave-like disturbances on the surfaces of vapour cores. Intense
sound at discrete frequencies can result from a coupling between tip vortex
disturbances and oscillating sheet cavitation on the surfaces of the propeller
blades. This research article focuses on the dynamics of vortex cavitation and
more in particular on the energy and frequency content of the radiated pressures.
PMID- 26442148
TI - Bubble dynamics in a compressible liquid in contact with a rigid boundary.
AB - A bubble initiated near a rigid boundary may be almost in contact with the
boundary because of its expansion and migration to the boundary, where a thin
layer of water forms between the bubble and the boundary thereafter. This
phenomenon is modelled using the weakly compressible theory coupled with the
boundary integral method. The wall effects are modelled using the imaging method.
The numerical instabilities caused by the near contact of the bubble surface with
the boundary are handled by removing a thin layer of water between them and
joining the bubble surface with its image to the boundary. Our computations
correlate well with experiments for both the first and second cycles of
oscillation. The time history of the energy of a bubble system follows a step
function, reducing rapidly and significantly because of emission of shock waves
at inception of a bubble and at the end of collapse but remaining approximately
constant for the rest of the time. The bubble starts being in near contact with
the boundary during the first cycle of oscillation when the dimensionless stand
off distance gamma = s/R m < 1, where s is the distance of the initial bubble
centre from the boundary and R m is the maximum bubble radius. This leads to (i)
the direct impact of a high-speed liquid jet on the boundary once it penetrates
through the bubble, (ii) the direct contact of the bubble at high temperature and
high pressure with the boundary, and (iii) the direct impingement of shock waves
on the boundary once emitted. These phenomena have clear potential to damage the
boundary, which are believed to be part of the mechanisms of cavitation damage.
PMID- 26442150
TI - Rapid identification of carbapenemase-producing Enterobacteriaceae, Pseudomonas
aeruginosa and Acinetobacter baumannii using a modified Carba NP test.
AB - Biochemical tests have been previously developed to identify carbapenemase
producing Enterobacteriaceae, Pseudomonas spp. (Carba NP test) and Acinetobacter
spp. (CarbAcineto NP test). We evaluated a modified Carba NP test to detect
carbapenemase production in Enterobacteriaceae, Pseudomonas and Acinetobacter
species using a single protocol with rapid results and found good reliability and
speed.
PMID- 26442151
TI - First fatal case of CNS infection caused by Enterovirus A in Brazil.
AB - We describe what is to our knowledge the first fatal case of central nervous
system Enterovirus infection in Brazil. Molecular and phylogenetic
characterization revealed that Enterovirus A was the aetiologic agent of this
case.
PMID- 26442149
TI - The bacterial pangenome as a new tool for analysing pathogenic bacteria.
AB - The bacterial pangenome was introduced in 2005 and, in recent years, has been the
subject of many studies. Thanks to progress in next-generation sequencing
methods, the pangenome can be divided into two parts, the core (common to the
studied strains) and the accessory genome, offering a large panel of uses. In
this review, we have presented the analysis methods, the pangenome composition
and its application as a study of lifestyle. We have also shown that the
pangenome may be used as a new tool for redefining the pathogenic species. We
applied this to the Escherichia coli and Shigella species, which have been a
subject of controversy regarding their taxonomic and pathogenic position.
PMID- 26442152
TI - Novel strain of Shigella dysenteriae serotype 7 from India.
AB - We describe a strain of Shigella dysenteriae serotype 7 which had novel
biochemical and genetic characters. Unlike other S. dysenteriae, it produced gas,
fermented mannitol, was a late-lactose fermenter and harboured the set 1A and set
1B genes. The significance of such atypical strains is that they are difficult to
identify. If such strains are missed, they could prove to be a serious public
health problem because the infectious dose is very low and they may harbour
integrons contributing to drug resistance.
PMID- 26442153
TI - Epidemiology of community-onset bloodstream infections in Bouake, central Cote
d'Ivoire.
AB - Bacterial bloodstream infections (BSI) account for considerable morbidity
worldwide, but epidemiological data from resource-constrained tropical settings
are scarce. We analysed 293 blood cultures from patients presenting to a regional
referral hospital in Bouake, central Cote d'Ivoire, to determine the aetiology of
community-onset BSI. The prevalence of bacteraemia was 22.5%, with children being
most commonly affected. Enterobacteriaceae (predominantly Klebsiella pneumoniae
and Salmonella enterica) accounted for 94% of BSI. Staphylococcus aureus was the
only relevant Gram-positive pathogen. Clinical signs and symptoms were not
significantly associated with blood culture positivity after controlling for
malaria.
PMID- 26442154
TI - Excessive adiposity, metabolic health, and risks for genital human papillomavirus
infection in adult women: a population-based cross-sectional study.
AB - BACKGROUND: The role of excessive adiposity or its metabolic consequences in
persistent HPV infection among general adult women remains unknown. METHODS:
Using data from the National Health and Nutrition Examination Survey (NHANES) in
2003-2010, we compared adult women's likelihood for any- or high-risk (HR) type
HPV infection by degrees of excessive adiposity and metabolic health status.
RESULTS: Any-type (41.1 % vs. 44.9 %, P = 0.045) or HR-type HPV prevalence (21.9
% vs. 25.4 %, P = 0.055) was comparable in women aged 20-59 years with or without
central obesity. After adjusting for age, socioeconomic indicators, and lifetime
sexual risks, centrally-obese women barely showed a different likelihood for any
type (aPR [adjusted prevalence ratio] = 0.91, P = 0.03) or HR-HPV infection (aPR
= 0.92, P = 0.279). However, obesity (aPR = 0.76, P = 0.017) or centrally-obesity
(aPR = 0.72, P = 0.003) was negatively correlated with HR-HPV infection in women
reporting an early sex debut (<16 years; P for interaction <0.05). In the fasting
subpopulation, obesity (aPR = 0.77, P = 0.016) or metabolically unhealthy obesity
(aPR = 0.69, P = 0.018) was significantly correlated with a 23 % or 31 % reduced
prevalence of HR-HPV infection. DISCUSSION: In contrary to findings for the
general population, HR-HPV prevalence was decreased in a subgroup of women with
obesity or central obesity. Possible explanations for such heterogeneity included
less risky sexual behaviors, an altered immune milieu that promoted viral
clearance, and increased access to healthcare resources due to other obesity
related co-morbidities in this subpopulation. CONCLUSIONS: Obesity or central
obesity was not significantly associated with prevalent any-type or HR-type HPV
infection among adult women in general. However, in certain subpopulations,
excessive adiposity or its relevant metabolic dysfunction was negatively
associated with HR-HPV infection.
PMID- 26442155
TI - Assessment of growth performance and meat quality of finishing pigs raised on the
low plane of nutrition.
AB - This study was performed to investigate the effects of the low plane of nutrition
on growth and meat quality of finishing pigs. A total of 136 crossbred barrows
and gilts weighing approximately 55 kg were allotted to 8 pens, with 17 animals
housed per pen, in a 2 (sex) * 2 (nutrition) factorial arrangement of treatments.
The animals allotted to a medium plane of nutrition (MPN) received a finisher
phase 1 (P1) diet containing 3.47 Mcal DE/kg and 0.92 % lysine and a P2 diet
containing 3.40 Mcal DE/kg and 0.78 % lysine for 35 d and 36/43 d, respectively;
the animals allotted to the low plane of nutrition (LPN) received only a P2 diet
containing 3.00 Mcal DE/kg and 0.68 % lysine 7 d longer than MPN. The animals
were slaughtered following the feeding trial, after which the loin, ham, Boston
butt, and belly were taken from a total of 24 animals, with the average live
weight being 120 kg, and their physicochemical and sensory quality traits were
analyzed. Average daily gain did not differ between MPN and LPN during either P1
or P2. Average daily feed intake was greater (P < 0.05) in LPN vs. MPN during
both phases whereas the opposite was true for the gain:feed ratio. Backfat
thickness (BFT) was less in LPN vs. MPN (21.7 vs. 24.1 mm at 115 kg). The plane
of nutrition influenced no effect on any of the physicochemical characteristics
of fresh loin, ham, or Boston butt analyzed in the present study. Fresh hams from
LPN exhibited superior aroma and odor scores than those from MPN; however,
sensory quality traits were not influenced by the plane of nutrition in other
fresh primal cuts or cooked meat. Instead, fresh primal cuts and cooked meat from
gilts rendered superior physicochemical characteristics and sensory scores,
respectively, than those from barrows. Results suggest that the low plane of
nutrition may be useful to increase the slaughter weight of finishing pigs with a
moderately high BFT by virtue of its BFT-lowering effect with or without exerting
a slightly positive influence on pork quality.
PMID- 26442156
TI - Social Support and Self-Reported Stress Levels in a Predominantly African
American Sample of Women with Systemic Lupus Erythematosus.
AB - Lupus patients should avoid stress because physical or emotional stress can
affect overall physical health. It has been suggested that social support has a
positive influence on health status, but there is a lack of information in the
literature on the association between the two among lupus patients. The current
study investigated the association between social support and self-reported
stress and coping status among African American women with lupus using data
collected from two linked cross-sectional surveys. No social support differences
in groups of high and low stress/coping were revealed; a duplicate study with a
larger sample size is required.
PMID- 26442157
TI - Association of IFN-gamma : IL-10 Cytokine Ratio with Nonsegmental Vitiligo
Pathogenesis.
AB - Background and Objectives. Cytokines regulate immune response and inflammation
and play a crucial role in depigmentation process of vitiligo. The present study
aimed to estimate the serum levels of pro- and anti-inflammatory cytokines, IFN
gamma and IL-10, and their ratios in nonsegmental vitiligo patients and healthy
individuals from India. Methods. Blood samples were collected from 280 subjects
and serum IFN-gamma and IL-10 levels were measured using standard ELISA. Results.
Nonsegmental vitiligo patients showed increased levels of IFN-gamma (12.4 +/- 3.2
versus 9.9 +/- 4.4 pg/mL) and decreased levels of IL-10 (9.3 +/- 1.7 versus 11.5
+/- 5 pg/mL) compared to controls. Ratio of IFN-gamma : IL-10 differed
significantly from patients to controls (p < 0.05). IFN-gamma concentrations and
IFN-gamma : IL-10 ratio varied significantly with respect to clinical variants,
disease stability, and social habits (smoking and alcohol consumption) and showed
a positive correlation with disease duration. Family history of vitiligo was
significantly associated with IFN-gamma : IL-10 ratio but not with their
individual levels. Conclusion. The ratio of IFN-gamma : IL-10 serum levels may be
considered as one of the promising immunological markers in nonsegmental
vitiligo. This is the first study considering multiple aspects in relation to
ratio of cytokine levels. Similar studies with large samples are warranted to
confirm our observations.
PMID- 26442158
TI - Gender Differences in the Appetite Response to a Satiating Diet.
AB - We examined gender differences in appetite sensations when exposed to
Mediterranean diet (MedDiet) meals and determined whether there are gender
differences in the change in the satiating properties of the MedDiet over time.
Thirty-eight men and 32 premenopausal women consumed a 4-week isoenergetic
MedDiet under controlled conditions. Visual analogue scales were used to measure
perceived appetite sensations before and immediately after each meal consumed
over the course of one day (Wednesday) of the first and the fourth week of
intervention. Women reported greater decreases for desire to eat, hunger, and
appetite score than men in response to the consumption of the MedDiet meals
(gender-by-meal interactions, resp., P = 0.04, P = 0.048, and P = 0.03). Fullness
and prospective food consumption responses did not significantly differ between
men and women. Between the first and the fourth week of intervention, premeal
prospective food consumption increased with time in men (P = 0.0007) but not in
women (P = 0.84; P for gender-by-time interaction = 0.04). These results indicate
gender differences in appetite sensations when exposed to the MedDiet. These
results may be useful in order to have a better understanding of gender issues
for body weight management.
PMID- 26442159
TI - Anatomical Study of Chiari Network and the Remnant of Left Venous Valve in the
Interior of Right Atrium.
AB - Chiari network occurs due to incomplete resorption of right valve of sinus
venosus. It is often noticed as fenestrated membranous structure or reticular
network like structure in the valve of inferior vena cava and coronary sinus. The
remnant of left venous valve is observed as trabeculae over the fossa ovalis. The
incidence of Chiari network and the remnant of left venous valve were studied in
80 cadaveric hearts utilized for teaching the undergraduates. The right atrium
was opened anterior to sulcus terminalis and the interior was examined for the
presence of these embryological remnants. The incidence of Chiari network and
left venous valve in the present study is 3.75% and 7.5%, respectively. Chiari
network was observed as a fenestrated membranous structure in 2 specimens and a
reticular network in 1 specimen, with variable extension to coronary sinus
opening and right atrial wall. The remnant of left venous valve was observed as
multiple fine strands in 3 specimens and trabecular structure in 3 specimens.
These structures may create diagnostic confusion, difficulty in interventional
procedures, and complications like thromboembolic events. Hence, the knowledge
about the incidence, morphology, and clinical manifestations of these rare
embryological remnants is mandatory.
PMID- 26442160
TI - The "Endothelialized Muscularis Mucosae": A Case Report Describing a Large
Cavernous Hemangioma at the Terminal Ileum and a New Histologic Clue for
Preoperative Diagnosis from Endoscopic Biopsy.
AB - Cavernous hemangiomas of the gastrointestinal tract are quite rare and, until
now, have been difficult to diagnose preoperatively due their nonspecific
presentations and imaging features, as well as a lack of histologic description
pertaining to small superficial biopsies such as those obtained endoscopically.
We report a unique case of a 4 cm transmural cavernous hemangioma in the terminal
ileum with literature review and describe a new histologic finding-the
"endothelialized muscularis mucosae," which was discovered upon review of the
endoscopic biopsy and could potentially facilitate preoperative diagnosis of
these lesions from endoscopic biopsies in the future. These lesions have
classically required surgical resection in order to make a definitive diagnosis
and rule out malignancy, with which they share many historical and radiographic
features. Due to their potential to cause bowel obstruction, intussusception,
perforation, and hemorrhage, these lesions may ultimately require surgical
resection to relieve symptoms or prevent or treat complications-however, surgical
planning and patient counseling could be greatly improved by a preoperative
diagnosis. Therefore, gastroenterologists, pathologists, and surgeons should be
aware of the "endothelialized muscularis mucosae" which can be very helpful in
diagnosing GI cavernous hemangiomas from endoscopic biopsies.
PMID- 26442161
TI - Systemic Sarcoidosis Mimicking a Behavioural Variant of Frontotemporal Dementia.
AB - Among rare neurological manifestations, a progressive dementia may exceptionally
be the revealing clinical feature of a sarcoidosis. Diagnosis may then be
difficult, especially when systemic signs are missing or latent, with a risk of
therapeutic delay. We report the first case of sarcoidosis mimicking a
frontotemporal dementia. A 53-year-old man presented with a dementia clinically
suggestive of frontotemporal dementia, progressing slowly for about 2 years.
However, MRI revealed unusual aspects, mainly large areas of T2/FLAIR hypersignal
within temporal regions and cerebellum, with nodular leptomeningeal and
juxtacortical Gadolinium enhancement. The patient was finally diagnosed with a
systemic sarcoidosis. We discuss the differential diagnosis based on MRI aspects
and review the literature on the clinical, biological, and imaging features of
sarcoidosis presenting with dementia. This case demonstrates that brain imaging
remains mandatory in the exploration process of a patient with dementia. Although
the patient presented with rather typical features of a behavioural variant of
frontotemporal dementia, the MRI aspect was the key exploration that leaded to
the diagnosis.
PMID- 26442162
TI - An Unusual Presentation of Adult Tethered Cord Syndrome Associated with Severe
Chest and Upper Back Pain.
AB - Adult tethered cord syndrome (ATCS) is a rare entity that usually presents with
multiple neurological symptoms, including lower extremity pain, backache, lower
extremity muscle weakness, and bowel/bladder disturbances. Prompt surgical
treatment is often necessary to avoid permanent sequelae. We report a 63-year-old
man with sudden-onset severe right chest and upper back pain, followed by urinary
retention. His initial workup included computed tomography of the abdomen and
pelvis, which showed a presacral mass. His symptom-driven neurological workup
focused on the cervical and thoracic spine, the results of which were normal.
Pelvic radiographs and magnetic resonance imaging of the lumbosacral spine showed
spina bifida occulta, meningocele, and presacral masses consistent with a
teratomatous tumor. His symptoms, except for urinary retention, improved
dramatically with surgical treatment. The excised specimen contained a
teratomatous lesion plus an organized hematoma. Hematoma formation was suspected
as the trigger of his sudden-onset right chest and upper back pain.
PMID- 26442163
TI - Noncholesteatomatous Cyst of the Tympanic Membrane: A Nonpublished Entity?
AB - Introduction. The presence of a serous cyst in the tympanic membrane implies the
description of a new or unpublished entity based on our knowledge whose origin
may be very unlikely explained on actual embryologic and anatomic background.
Clinical Case. We present a case of a 45-year-old woman with progressing right
hearing loss. Physical examination revealed a whitish, round-shaped malformation
in the posterior-inferior quadrant of the right tympanic membrane. The cyst was
removed with a transcanal tympanoplasty. Discussion. A thorough PubMed search
that involved the terms tympanic membrane gland, epithelial inclusion cysts,
mucous-secreting cyst, and tympanic cyst has shown no positive results. The first
description of an unknown entity, such as a tympanic membrane serous cyst, may be
the key for clinicians to start paying attention to patients who suffer from
similar pathologies and may pass unnoticed because of their rarity or
peculiarity.
PMID- 26442164
TI - A Pleural Solitary Fibrous Tumor, Multiple Gastrointestinal Stromal Tumors,
Moyamoya Disease, and Hyperparathyroidism in a Patient Associated with NF1.
AB - Neurofibromatosis type 1 (NF1), also called von Recklinghausen's disease, is a
multisystemic disease caused by an alteration of the NF1 gene, a tumor suppressor
located on the long arm of chromosome 17 (17q11.2). Loss of the gene function,
due to a point mutation, leads to an increase in cell proliferation and the
development of several tumors. We report a 60-year-old female patient manifesting
hypercalcemia due to hyperparathyroidism, a solitary fibrous tumor (SFT) of the
pleura, multiple gastrointestinal stromal tumors (GISTs), and moyamoya disease
associated with NF1. The SFT and GISTs were removed by staged operations. Then,
hypercalcemia was successfully controlled after resection of the parathyroid
adenoma. Based on a literature review, these combinations have never been
reported, and the relevant literature is briefly discussed.
PMID- 26442165
TI - Asymptomatic Glomus Tumor of the Mediastinum.
AB - Glomus tumors are rare benign neoplasms that predominate in limbs. Infrequently,
they can occur in a wide anatomic distribution, to include sites not known to
contain glomus cells. Although glomus tumors are usually small, pain and
tenderness are common clinical symptoms. We report the case of a 69-year-old man
with an asymptomatic large mediastinal glomus tumor, who underwent surgical
resection.
PMID- 26442166
TI - Stereotactic Body Radiotherapy for Localized Ureter Transitional Cell Carcinoma:
Three Case Reports.
AB - The gold standard management for ureter transitional cell carcinoma (UTCC) is
radical nephroureterectomy with excision of the bladder cuff. However, some
patients cannot undergo this procedure for several reasons. In the case reports
described herein, we performed stereotactic body radiotherapy (SBRT) on three
patients with inoperable or surgery-rejected localized UTCC. Two out of the three
patients did not develop local recurrence or distant metastasis during the
observation period. However, recurrence was detected in the bladder of one
patient 22 months after the treatment. No acute or late adverse events occurred
in any of the three patients. SBRT may become one of the treatment options for
inoperable or surgery-rejected UTCC patients.
PMID- 26442167
TI - Bioaccumulation of Antimony and Arsenic in Vegetables and Health Risk Assessment
in the Superlarge Antimony-Mining Area, China.
AB - Heavy metal pollution in soils caused by mining and smelting has attracted
worldwide attention for its potential health risks to residents. This paper
studies the concentrations and accumulations of Sb and As in both soils and
vegetables and the human health risks of Sb and As in vegetables from Xikuangshan
(XKS) Sb mine, Hunan, China. Results showed that the soils were severely polluted
by Sb and As; Sb and As have significant positive correlation. Sb and As
concentrations in vegetables were quite different: Coriandrum sativum L. was the
highest in Sb, Allium fistulosum L. was the highest in As, and Brassica
pekinensis L. was the lowest in both Sb and As; Daucus carota L. and Coriandrum
sativum L. showed advantage in accumulating Sb and As; Coriandrum sativum L. had
higher capacity of redistributing Sb and As within the plant. Health risk
assessment results showed that the hazard quotient (HQ) values of Sb and As in
vegetables were in the ranges of 1.61-3.33 and 0.09-0.39, respectively; the
chronic daily intake (CDI) and hazard quotient (HQ) values of Sb were over the
safe limit recommended by FAO and WHO, indicating that long-term consumption of
vegetables from the surrounding soils of XKS mine may bring health risks to
residents.
PMID- 26442168
TI - Postoperative Autologous Reinfusion in Total Knee Replacement.
AB - Surgeries for total knee replacement (TKR) are increasing and in this context
there is a need to develop new protocols for management and use of blood
transfusion therapy. Autologous blood reduces the need for allogeneic blood
transfusion and the aim of the present study was to verify the safety and the
clinical efficacy. An observational retrospective study has been conducted on 124
patients, undergoing cemented total knee prosthesis replacement. Observed
population was stratified into two groups: the first group received reinfusion of
autologous blood collected in the postoperative surgery and the second group did
not receive autologous blood reinfusion. Analysis of data shows that patients
undergoing autologous blood reinfusion received less homologous blood bags (10.6%
versus 30%; p = 0.08) and reduced days of hospitalization (7.88 +/- 0.7 days
versus 8.96 +/- 2.47 days for the control group; p = 0.03). Microbiological tests
were negative in all postoperatively salvaged and reinfused units. Our results
emphasize the effectiveness of this procedure and have the characteristics of
simplicity, low cost (?97.53 versus ?103.79; p < 0.01), and easy reproducibility.
Use of autologous drainage system postoperatively is a procedure that allows
reducing transfusion of homologous blood bags in patients undergoing TKR.
PMID- 26442169
TI - Mining hidden polymorphic sequence motifs from divergent plant helitrons.
AB - As a major driving force of genome evolution, transposons have been deviating
from their original connotation as "junk" DNA ever since their important roles
were revealed. The recently discovered Helitron transposons have been
investigated in diverse eukaryotic genomes because of their remarkable gene
capture ability and other features that are crucial to our current understanding
of genome dynamics. Helitrons are not canonical transposons in that they do not
end in inverted repeats or create target site duplications, which makes them
difficult to identify. Previous methods mainly rely on sequence alignment of
conserved Helitron termini or manual curation. The abundance of Helitrons in
genomes is still underestimated. We developed an automated and generalized tool,
HelitronScanner, that identified a plethora of divergent Helitrons in many plant
genomes. A local combinational variable approach as the key component of
HelitronScanner offers a more granular representation of conserved nucleotide
combinations and therefore is more sensitive in finding divergent Helitrons. This
commentary provides an in-depth view of the local combinational variable approach
and its association with Helitron sequence patterns. Analysis of Helitron
terminal sequences shows that the local combinational variable approach is an
efficacious representation of nucleotide patterns imperceptible at a full
sequence level.
PMID- 26442170
TI - Assembly and characterization of novel Alu inserts detected from next-generation
sequencing data.
AB - Repetitive elements generally, and Alu inserts specifically are a large
contributor to the recent evolution of the human genome. By assembling the
sequences of novel Alu inserts using their respective subfamily consensus
sequences as references, we found an exponential decay in the Alu subfamily call
enrichment with increased number of sequence variants (Pearson correlation
[Formula: see text], [Formula: see text]). By mapping the sequences of these
inserts to a human reference genome, we infer the reference Alu sources of a
subset of the novel Alus, of which 85% were previously shown to be active. We
also evaluate relationships between the loci of the novel inserts and their
inferred sources.
PMID- 26442171
TI - An assay to monitor the activity of DNA transposition complexes yields a general
quality control measure for transpositional recombination reactions.
AB - Transposon-based technologies have many applications in molecular biology and can
be used for gene delivery into prokaryotic and eukaryotic cells. Common
transpositional activity measurement assays suitable for many types of
transposons would be beneficial, as diverse transposon systems could be compared
for their performance attributes. Therefore, we developed a general-purpose assay
to enable and standardize the activity measurement for DNA transposition
complexes (transpososomes), using phage Mu transposition as a test platform. This
assay quantifies transpositional recombination efficiency and is based on an in
vitro transposition reaction with a target plasmid carrying a lethal ccdB gene.
If transposition targets ccdB, this gene becomes inactivated, enabling plasmid
receiving Escherichia coli cells to survive and to be scored as colonies on
selection plates. The assay was validated with 3 mini-Mu transposons varying in
size and differing in their marker gene constitution. Tests with different
amounts of transposon DNA provided a linear response and yielded a 10-fold
operational range for the assay. The colony formation capacity was linearly
correlated with the competence status of the E.coli cells, enabling normalization
of experimental data obtained with different batches of recipient cells. The
developed assay can now be used to directly compare transpososome activities with
all types of mini-Mu transposons, regardless of their aimed use. Furthermore, the
assay should be directly applicable to other transposition-based systems with a
functional in vitro reaction, and it provides a dependable quality control
measure that previously has been lacking but is highly important for the
evaluation of current and emerging transposon-based applications.
PMID- 26442172
TI - Rebooting the genome: The role of negative feedback in horizontal gene transfer.
AB - Horizontal Gene Transfer (HGT) is one of the key mechanisms driving bacterial
evolution. Conjugative plasmids are fundamental vehicles for HGT in bacteria,
playing an essential role in the spread of antibiotic resistances. Although the
classical view has stressed the instrumental role of these mobile genetic
elements in the dissemination of antibiotic resistance genes, plasmids contain a
rich physiology devoted to horizontal and vertical reproduction. This particular
lifestyle imposes specific constrains and trade-offs on plasmid physiology, and
plasmids have evolved dedicated circuits to balance the opposing demands of
vertical and horizontal reproduction. Recent studies on the transcriptional
networks of IncW plasmids and other incompatibility groups have unveiled common
architectures in the regulatory networks of different plasmid groups. Comparative
studies show that negative feedback loops (NFLs) with strong gains are preferred,
opening the question of a possible convergent evolution dictated by certain
adaptive properties of this particular network motif. System analysis of NFLs
with strong feedback gains indicate that this architecture exhibits transient
overshooting after horizontal gene transfer. Since plasmid burden is dependent on
the expression of plasmid functions, transcriptional overshooting results in a
transient increase of the burden immediately after conjugation. We discuss the
possible implications of this phenomenon on plasmid propagation, and the
regulatory networks that plasmids have evolved to counteract the detrimental side
effects of transient overshooting.
PMID- 26442173
TI - Applications of DNA integrating elements: Facing the bias bully.
AB - Retroviruses and DNA transposons are an important part of molecular biologists'
toolbox. The applications of these elements range from functional genomics to
oncogene discovery and gene therapy. However, these elements do not integrate
uniformly across the genome, which is an important limitation to their use. A
number of genetic and epigenetic factors have been shown to shape the integration
preference of these elements. Insight into integration bias can significantly
enhance the analysis and interpretation of results obtained using these elements.
For three different applications, we outline how bias can affect results, and can
potentially be addressed.
PMID- 26442174
TI - Autonomous and non-autonomous Tn3-family transposons and their role in the
evolution of mobile genetic elements.
AB - The Tn3 family of transposons includes diverse elements that encode homologous
transposases and contain conserved terminal inverted repeat sequences (IRs). The
recent identification of non-autonomous elements, named TIMEs (Tn3-derived
Inverted-repeat Miniature Elements), has shed new light on the diversity and
evolution of this transposon family. A common feature of TIMEs and other members
of this family is their ability to mobilize genomic DNA for transposition as part
of composite transposons. These elements significantly influence the structure
and properties of plasmids and other mobile genetic elements (MGEs). They may
contain and move by transposition (i) plasmid replication systems, (ii) toxin
antitoxin systems and (iii) site-specific recombination modules that can resolve
plasmid multimers. Some Tn3 family elements may also transfer large segments of
chromosomal DNA into plasmids, which increases the pool of mobile DNA that can
take part in horizontal gene transfer.
PMID- 26442175
TI - Endogenous retrovirus-mediated genomic variations in chimpanzees.
AB - Transposable elements (TEs) have played a significant role in the evolution of
host genome by triggering genomic rearrangements. TEs have been studied in
various research fields, ranging from population genomics to personalized
medicines. Human-specific TEs and TEs existing in the human genome have been well
studied. Unlike them, non-human primate-specific TEs remain shrouded in mystery.
However, the study of TE-mediated genomic or genetic variations through
comparative genomics is essential to understand mechanisms which TEs utilize to
modify species-specific genome architecture and to cause species-specific
diseases, Therefore, we have studied chimpanzee-specific TEs as well as human
specific TEs. At first, we identified human-specific HERV-K integrated into the
human genome after the divergence of human and chimpanzee. Then, for a
comparative study of HERV-Ks and non-human ERVs, we extracted chimpanzee-specific
endogenous retroviruses (PtERVs) from the chimpanzee genome. We identified 256
chimpanzee-specific PtERVs and characterized them, focusing on their estimated
evolutionary age, polymorphism level in chimpanzee populations, and potential
impact on the difference between the human and chimpanzee genomes.
PMID- 26442176
TI - Drawing a fine line on endogenous retroelement activity.
AB - Endogenous retroelements (EREs) are essential motors of evolution yet require
careful control to prevent genomic catastrophes, notably during the vulnerable
phases of epigenetic reprogramming that occur immediately after fertilization and
in germ cells. Accordingly, a variety of mechanisms restrict these mobile genetic
units. Previous studies have revealed the importance of KRAB-containing zinc
finger proteins (KRAB-ZFPs) and their cofactor, KAP1, in the early embryonic
silencing of endogenous retroviruses and so-called SVAs, but the implication of
this transcriptional repression system in the control of LINE-1, the only known
active autonomous retrotransposon in the human genome, was thought to be
marginal. Two recent studies straighten the record by revealing that the KRAB/KAP
system is key to the control of L1 in embryonic stem (ES) cells, and go further
in demonstrating that DNA methylation and KRAB/KAP1-induced repression contribute
to this process in an evolutionally dynamic fashion. These results shed light on
the delicate equilibrium between higher vertebrates and endogenous retroelements,
which are not just genetic invaders calling for strict control but rather a
constantly renewed and nicely exploitable source of evolutionary potential.
PMID- 26442177
TI - Integration of erm(B)-containing elements through large chromosome fragment
exchange in Clostridium difficile.
AB - In Clostridium difficile, erm(B) genes are located on mobile elements like Tn5398
and Tn6215. In previous studies, some of these elements were transferred by
conjugation-like mechanisms, mobilized in trans by helper conjugative systems. In
this study, we analyzed the genomes of several recipient strains that acquired
either Tn5398 or Tn6215-like elements. We demonstrated that the integration of
the transposons in the genome of the recipient cell was always due to homologous
recombination events, involving exchange of large chromosomal segments. We did
not observed transposon transfer to a C. difficile strain in presence of DNAse,
suggesting that a possible transformation-like mechanism occurred in this
recipient.
PMID- 26442179
TI - The "complex" RNA post-transcriptional element of a "simple" retrovirus.
AB - Replication of retroviruses and transposition of endogenous retroelements
exploits a unique mechanism of post-transcriptional regulation as a means of
exporting their incompletely-spliced mRNAs (which serve as both the genomic RNA
and the template for protein synthesis). Following discovery of the Rev response
element (RRE) that mediates nucleocytoplasmic export of the full-length and
singly-spliced human immunodeficiency virus type 1 (HIV-1) genome, equivalent cis
acting regulatory elements have been characterized for both complex and simple
retroviruses and retroelements, together with the obligate viral and host
proteins with which they interact. The exception to this is the gammaretrovirus
family of simple retroviruses, exemplified by reticuloendotheliosis virus (REV),
murine leukemia virus (MLV) and xenotropic MLV-related retrovirus (XMRV). In this
commentary, we discuss our recent data that reported structural and functional
data on the MLV/XMRV post-transcriptional regulatory element (designated the
PTE). The PTE was characterized by a highly-structured region of multiple stem
loops (SL1 - SL7) overlapping the pro and 5' portion of the pol open reading
frames, comprising a bipartite export signal whose structures are separated by
~1400 nt. In addition, structural probing suggested that SL3 nucleotides were
involved in pseudoknot formation. These data, when compared with RNA transport
elements of complex retroviruses (HIV) and simple murine retrotransposons (musD),
collectively present an emerging picture that long-range tertiary interactions
are critical mediators of their biological function.
PMID- 26442178
TI - Stable persistence of the yeast plasmid by hitchhiking on chromosomes during
vegetative and germ-line divisions of host cells.
AB - The chromosome-like stability of the Saccharomyces cerevisiae plasmid 2 micron
circle likely stems from its ability to tether to chromosomes and segregate by a
hitchhiking mechanism. The plasmid partitioning system, responsible for
chromosome-coupled segregation, is comprised of 2 plasmid coded proteins Rep1 and
Rep2 and a partitioning locus STB. The evidence for the hitchhiking model for
mitotic plasmid segregation, although compelling, is almost entirely
circumstantial. Direct tests for plasmid-chromosome association are hampered by
the limited resolving power of current cell biological tools for analyzing yeast
chromosomes. Recent investigations, exploiting the improved resolution of yeast
meiotic chromosomes, have revealed the plasmid's propensity to be present at or
near chromosome tips. This localization is consistent with the rapid plasmid
movements during meiosis I prophase, closely resembling telomere dynamics driven
by a meiosis-specific nuclear envelope motor. Current evidence is consistent with
the plasmid utilizing the motor as a platform for gaining access to telomeres.
Episomes of viruses of the papilloma family and the gammaherpes subfamily persist
in latently infected cells by tethering to chromosomes. Selfish genetic elements
from fungi to mammals appear to have, by convergent evolution, arrived at the
common strategy of chromosome association as a means for stable propagation.
PMID- 26442180
TI - Evaluating the effect of horizontal transmission on the stability of plasmids
under different selection regimes.
AB - In theory, plasmids can only be maintained in a population when the rate of
horizontal gene transfer is larger than the combined effect of segregational loss
and the decrease of fitness associated with plasmid carriage. Recent advances in
genome sequencing have shown, however, that a large fraction of plasmids do not
carry the genes necessary for conjugation or mobilization. So, how are so-called
non-transmissible plasmids able to persist? In order to address this question, we
examined a previously published evolutionary model based on the interaction
between P. aeruginosa and the non-transmissible plasmid pNUK73. Both our in
silico and in vitro results demonstrated that, although compensatory adaptation
can decrease the rate of plasmid decay, the conditions for the maintenance of a
non-transmissible plasmid are very stringent if the genes it carries are not
beneficial to the bacterial host. This result suggests that apparently non
transmissible plasmids may still experience episodes of horizontal gene transfer
occurring at very low frequencies, and that these scattered transmission events
are sufficient to stabilize these plasmids. We conclude by discussing different
genomic and microbiological approaches that could allow for the detection of
these rare transmission events and thus to obtain a reliable estimate of the rate
of horizontal gene transfer.
PMID- 26442181
TI - Repetitive elements regulate circular RNA biogenesis.
AB - It was long assumed that eukaryotic precursor mRNAs (pre-mRNAs) are almost always
spliced to generate a linear mRNA that is subsequently translated to produce a
protein. However, it is now clear that thousands of protein-coding genes can be
non-canonically spliced to produce circular noncoding RNAs, some of which are
expressed at much higher levels than their associated linear mRNAs. How then does
the splicing machinery decide whether to generate a linear mRNA or a circular
RNA? Recent work has revealed that intronic repetitive elements, including
sequences derived from transposons, are critical regulators of this decision. In
most cases, circular RNA biogenesis appears to be initiated when complementary
sequences from 2 different introns base pair to one another. This brings the
splice sites from the intervening exon(s) into close proximity and facilitates
the backsplicing event that generates the circular RNA. As many pre-mRNAs contain
multiple intronic repeats, distinct circular transcripts can be produced
depending on which repeats base pair to one another. Intronic repeats are thus
critical regulatory sequences that control the functional output of their host
genes, and potentially cause the functions of protein-coding genes to be highly
divergent across species.
PMID- 26442182
TI - LINE-1 activity as molecular basis for genomic instability associated with light
exposure at night.
AB - The original hypothesis that exposure to light at night increases risk of breast
cancer via suppression of nocturnal melatonin production was proposed over 2
decades ago. In 2007, shift work that involves circadian disruption has been
recognized by the World Health Organization as a probable human carcinogen. Our
discovery of melatonin-dependent regulation of LINE-1 retrotransposon expression
and mobilization is the latest addition to the list of cellular genes and
processes that are affected by light exposure at night. This finding establishes
an unexpected health relevant connection between this endogenous DNA damaging
agent and environmental light exposure. It also offers an appealing hypothesis
pertaining to the origin of genomic instability in the genomes of individuals
with light at night- or age-associated disruption of melatonin signaling.
PMID- 26442183
TI - Unraveling the regulatory network of IncA/C plasmid mobilization: When genomic
islands hijack conjugative elements.
AB - Conjugative plasmids of the A/C incompatibility group (IncA/C) have become
substantial players in the dissemination of multidrug resistance. These large
conjugative plasmids are characterized by their broad host-range, extended
spectrum of antimicrobials resistance, and prevalence in enteric bacteria
recovered from both environmental and clinical settings. Until recently,
relatively little was known about the basic biology of IncA/C plasmids, mostly
because of the hindrance of multidrug resistance for molecular biology
experiments. To circumvent this issue, we previously developed pVCR94DeltaX, a
convenient prototype that codes for a reduced set of antibiotic resistances.
Using pVCR94DeltaX, we then characterized the regulatory pathway governing IncA/C
plasmid dissemination. We found that the expression of roughly 2 thirds of the
genes encoded by this plasmid, including large operons involved in the
conjugation process, depends on an FlhCD-like master activator called AcaCD.
Beyond the mobility of IncA/C plasmids, AcaCD was also shown to play a key role
in the mobilization of different classes of genomic islands (GIs) identified in
various pathogenic bacteria. By doing so, IncA/C plasmids can have a considerable
impact on bacterial genomes plasticity and evolution.
PMID- 26442184
TI - Get the jump - Do 3'UTRs protect transposable elements from silencing?
AB - Eukaryotic genomes contain large numbers of transposable elements and repetitive
sequences that are subjected to silencing through epigenetic mechanisms. These
involve primarily DNA methylation, chromatin modifications and small RNA. It is
known that these transposable elements can affect the expression of neighboring
genes; however, little is known about how transposable element silencing depends
on the general chromosomal environment at the insertion site. Taking advantage of
the vast genomic resources available in Arabidopsis thaliana, a recent report
begins to unravel these interactions by identifying insertion sites of one
specific MULE element, AtMu1c across the A. thaliana lineage. Among over 30
insertion sites analyzed, a correlation between the loss of epigenetic silencing
and the insertion into the 3'end of protein coding genes was found. Here, we
discuss details, implications and potential mechanisms of these findings that may
be applicable to a much wider set of transposable elements and across diverse
species.
PMID- 26442185
TI - The coelacanth: Can a "living fossil" have active transposable elements in its
genome?
AB - The coelacanth has long been regarded as a "living fossil," with extant specimens
looking very similar to fossils dating back to the Cretaceous period. The
hypothesis of a slowly or even not evolving genome has been proposed to account
for this apparent morphological stasis. While this assumption seems to be
sustained by different evolutionary analyses on protein-coding genes, recent
studies on transposable elements have provided more conflicting results. Indeed,
the coelacanth genome contains many transposable elements and has been shaped by
several major bursts of transposition during evolution. In addition, comparison
of orthologous genomic regions from the genomes of the 2 extant coelacanth
species L. chalumnae and L. menadoensis revealed multiple species-specific
insertions, indicating transposable element recent activity and contribution to
post-speciation genome divergence. These observations, which do not support the
genome stasis hypothesis, challenge either the impact of transposable elements on
organismal evolution or the status of the coelacanth as a "living fossil." Closer
inspection of fossil and molecular data indicate that, even if coelacanths might
evolve more slowly than some other lineages due to demographic and/or ecological
factors, this variation is still in the range of a "non-fossil" vertebrate
species.
PMID- 26442186
TI - Comparison of methods for the determination of the transposition rate of mobile
elements.
AB - There is wide-spread interest in understanding the rate of transposable element
movement within populations and between species. A recent study using
interprecific crosses between D. buzzatii and D. koepferae indicated that
transposition rates in hybrids may be quite high. However, we suggest caution
should be taken in this interpretation since AFLP methods to detect transposition
events may lead to overestimated rate estimates. Comparative analyses of genome
instability received by different methods suggest that transposition rates can be
higher in intraspecific crosses compared to interspecific crosses.
PMID- 26442187
TI - The lambda - P22 problem.
AB - Lambda and P22 are members of 2 families of tailed phages and have limited
genomic relationships. Both form hybrids with many phages. P22 appears as a
hybrid of mixed ancestry. Despite their similarities, lambda and P22 and their
relatives form 2 distinct lineages and must be classified separately.
PMID- 26442188
TI - Phage therapy of pulmonary infections.
AB - It is generally agreed that a bacteriophage-associated phenomenon was first
unambiguously observed one-hundred years ago with the findings of Twort in 1915.
This was independently followed by complementary observations by d'Herelle in
1917. D'Herelle's appreciation of the bacteriophage phenomenon appears to have
directly led to the development of phages as antibacterial agents within a
variety of contexts, including medical and agricultural. Phage use to combat
nuisance bacteria appears to be especially useful where targets are sufficiently
problematic, suitably bactericidal phages exist, and alternative approaches are
lacking in effectiveness, availability, safety, or cost effectiveness, etc. Phage
development as antibacterial agents has been strongest particularly when
antibiotics have been less available or useful, e.g., such as in the treatment of
chronic infections by antibiotic-resistant bacteria. One relatively under
explored or at least not highly reported use of phages as therapeutic agents has
been to combat bacterial infections of the lungs and associated tissues. These
infections are diverse in terms of their etiologies, manifestations, and also in
terms of potential strategies of phage delivery. Here I review the literature
considering the phage therapy of pulmonary and pulmonary-related infections, with
emphasis on reports of clinical treatment along with experimental treatment of
pulmonary infections using animal models.
PMID- 26442189
TI - Life In Science.
PMID- 26442190
TI - My life with Mu.
PMID- 26442191
TI - Giuseppe Bertani (1923-2015).
PMID- 26442192
TI - Life in science.
PMID- 26442193
TI - Serendipity and the times.
PMID- 26442194
TI - Bioinformatics as a first-line approach for understanding bacteriophage
transcription.
AB - Current approach to understanding bacteriophage transcription strategies during
infection includes a combination of experimental and bioinformatics approaches,
which is often time and resource consuming. Given the exponentially growing
number of sequenced bacteriophage genomes, it becomes sensible asking to what
extent one can understand bacteriophage transcription by using bioinformatics
methods alone. We here argue that a suitable choice of computational methods may
provide a highly efficient first-line approach for underst-anding bacteriophage
transcription.
PMID- 26442195
TI - Phage on the stage.
AB - The resurgence of interest in bacteriophages for use in combating antibiotic
resistant bacteria is coincident with an urgent call for more effective science
education practices, including hands-on learning opportunities. To address this
issue, a number of solutions have been proposed, including a large educational
experiment, begun in 2007 by the Howard Hughes Medical Institute and currently
involving over 85 colleges and universities, which has students discovering
unique phages, obtaining images, and purifying phage DNA. A subset of these phage
genomes is sequenced and analyzed using bioinformatics tools. Papers describing
individual phage discoveries and comparative genomic studies are being published
regularly. The vast majority of students in the program are in their first year
of college, a critical time in capturing their interest and retaining them as
science majors. This viral discovery model is being adopted and modified by a
wide variety of educational institutions using a number of different bacterial
hosts. In the opinion of the authors, this program and others like it represent a
model accessible to virtually any undergraduate setting. And because of these
programs, bacteriophage enthusiasts (academics, health professionals,
biotechnology companies) can look forward to more well prepared students entering
their ranks and should anticipate many more potentially useful phages discovered
and characterized.
PMID- 26442197
TI - C. elegans sirtuin SIR-2.4 and its mammalian homolog SIRT6 in stress response.
AB - Stress is a significant life event. The immediate response to stress is critical
for survival. In organisms ranging from the unicellular Saccharomyces cerevisiae
to protozoa (Trypanosoma brucei) and metazoan (such as Caenorhabditis elegans,
Homo sapiens) stress response leads to the formation of cytoplasmic RNA-protein
complexes referred to as stress granules (SGs). SGs regulate cell survival during
stress by the sequestration of the signaling molecules implicated in apoptosis.
They are a transient place of messenger ribonucleoproteins (mRNPs) remodeling for
storage, degradation, or reinitiation of translation during stress and recovery
from stress. Recently, we have identified chromatin factor, the sirtuin C.
elegans SIR-2.4 variant and its mammalian homolog SIRT6 as a regulator of SGs
formation. SIRT6 is highly conserved NAD(+)-dependent lysine deacetylase and ADP
ribosyltransferase impacting longevity, metabolism, and cancer. We observed that
the cellular formation of SGs by SIRT6 or SIR-2.4 was linked with the cell
viability or C. elegans survival and was dependent on SIRT6 enzymatic activity.
Here, we discuss how SIR-2.4/SIRT6 influences SGs formation and stress response.
We suggest possible mechanisms for such an unanticipated function of a chromatin
regulatory factor SIRT6 in assembly of stress granules and cellular stress
resistance.
PMID- 26442196
TI - Antimicrobial bacteriophage-derived proteins and therapeutic applications.
AB - Antibiotics have the remarkable power to control bacterial infections.
Unfortunately, widespread use, whether regarded as prudent or not, has favored
the emergence and persistence of antibiotic resistant strains of human pathogenic
bacteria, resulting in a global health threat. Bacteriophages (phages) are
parasites that invade the cells of virtually all known bacteria. Phages reproduce
by utilizing the host cell's machinery to replicate viral proteins and genomic
material, generally damaging and killing the cell in the process. Thus, phage can
be exploited therapeutically as bacteriolytic agents against bacteria.
Furthermore, understanding of the molecular processes involved in the viral life
cycle, particularly the entry and cell lysis steps, has led to the development of
viral proteins as antibacterial agents. Here we review the current preclinical
state of using phage-derived endolysins, virion-associated peptidoglycan
hydrolases, polysaccharide depolymerases, and holins for the treatment of
bacterial infection. The scope of this review is a focus on the viral proteins
that have been assessed for protective effects against human pathogenic bacteria
in animal models of infection and disease.
PMID- 26442199
TI - Rare disease diagnosis: A review of web search, social media and large-scale data
mining approaches.
AB - Physicians and the general public are increasingly using web-based tools to find
answers to medical questions. The field of rare diseases is especially
challenging and important as shown by the long delay and many mistakes associated
with diagnoses. In this paper we review recent initiatives on the use of web
search, social media and data mining in data repositories for medical diagnosis.
We compare the retrieval accuracy on 56 rare disease cases with known diagnosis
for the web search tools google.com, pubmed.gov, omim.org and our own search tool
findzebra.com. We give a detailed description of IBM's Watson system and make a
rough comparison between findzebra.com and Watson on subsets of the Doctor's
dilemma dataset. The recall@10 and recall@20 (fraction of cases where the correct
result appears in top 10 and top 20) for the 56 cases are found to be be 29%,
16%, 27% and 59% and 32%, 18%, 34% and 64%, respectively. Thus, FindZebra has a
significantly (p < 0.01) higher recall than the other 3 search engines. When
tested under the same conditions, Watson and FindZebra showed similar recall@10
accuracy. However, the tests were performed on different subsets of Doctors
dilemma questions. Advances in technology and access to high quality data have
opened new possibilities for aiding the diagnostic process. Specialized search
engines, data mining tools and social media are some of the areas that hold
promise.
PMID- 26442198
TI - Ribosomopathies: Global process, tissue specific defects.
AB - Disruptions in ribosomal biogenesis would be expected to have global and in fact
lethal effects on a developing organism. However, mutations in ribosomal protein
genes have been shown in to exhibit tissue specific defects. This seemingly
contradictory finding - that globally expressed genes thought to play fundamental
housekeeping functions can in fact exhibit tissue and cell type specific
functions - provides new insight into roles for ribosomes, the protein
translational machinery of the cell, in regulating normal development and
disease. Furthermore it illustrates the surprisingly dynamic nature of processes
regulating cell type specific protein translation. In this review, we discuss our
current knowledge of a variety of ribosomal protein mutations associated with
human disease, and models to better understand the molecular mechanisms
associated with each. We use specific examples to emphasize both the similarities
and differences between the effects of various human ribosomal protein mutations.
Finally, we discuss areas of future study that are needed to further our
understanding of the role of ribosome biogenesis in normal development, and
possible approaches that can be used to treat debilitating ribosomopathy
diseases.
PMID- 26442200
TI - A Perspective on Prostate Carcinogenesis and Chemoprevention.
AB - In this perspective, modifiable carcinogenic factors for the prostate are
summarized. This is followed by a discussion of how current knowledge about
causation of prostate cancer and chemoprevention of prostate cancer can be used
to develop preventive strategies. Prostate cancer is a slowly developing cancer
which offers opportunities for preventive interventions. Only a few randomized
clinical trials of prostate cancer prevention have been completed. The SELECT
study with selenium and vitamin E did not find protective effects, but in two
trials with 5alpha-reductase inhibitors risk was reduced about 25%, showing that
chemoprevention is possible and indicating that the androgen receptor is a
suitable target. Besides smoking cessation and reduction of obesity, there are no
known dietary or life style interventions that will have a major impact on
prostate cancer risk. Inflammation of the prostate is an attractive target and
aspirin may be a promising candidate agent, but has not been addressed yet in
preclinical and clinical studies. Antioxidants other than selenium and vitamin E
are unlikely to be very effective and data on several dietary supplements are not
encouraging. More candidate agents need to be identified and tested in relevant
and adequate preclinical models and Phase II trials that have predictive value
for outcome of Phase III randomized studies. Doing this will require a systematic
approach comparing preclinical and clinical study outcomes to determine their
predictive value of preventive efficacy.
PMID- 26442202
TI - Targeting the COX-2 Pathway to Improve Therapeutic Response in the Obese Breast
Cancer Patient Population.
AB - Multiple studies have demonstrated that obesity is associated with a worse
outcome for all breast cancer subtypes and that obese breast cancer patients do
not respond as well as normal weight patients to aromatase inhibitor treatment
and chemotherapy. While a number of mechanisms have been proposed to explain this
link, recent studies have provided evidence that elevated local cyclooxygenase-2
(COX-2) expression and the resulting increase in prostaglandin E2 (PGE2)
production may play an important role. COX-2 upregulation in breast tumors is
associated with a poor prognosis, a connection generally attributed to PGE2's
direct effects on apoptosis and invasion as well as its stimulation of pre
adipocyte aromatase expression and subsequent estrogen production. Research in
this area has provided a strong foundation for the hypothesis that COX-2
signaling is involved in the obesity-breast cancer link, and further study
regarding the role of COX-2 in this link is warranted.
PMID- 26442201
TI - Targeting HER2 Positive Breast Cancer with Chemopreventive Agents.
AB - Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a
subtype of breast cancer that is exhibited in approximately 20-30% of breast
cancer cases. The overexpression of HER2 is typically associated with a more
aggressive disease and poor prognosis. Currently, the therapeutic drugs
trastuzumab and lapatinib are the most commonly used to combat HER2+ breast
cancer. However, tumors can develop resistance to these drugs. A better
understanding of the mechanism of how HER2+ breast cancer works will help aid the
development for new therapeutic approaches which more closely target the source
of the signaling dysfunction. This review summarizes four major points in the
context of HER2 over-expressing breast cancer (i) HER2 as a molecular target in
breast cancer therapy, (ii) current treatment options as well as ongoing clinical
studies, (iii) animal and cellular models for the study of HER2 over-expressing
breast cancer, and (iv) future therapies and chemopreventive agents used to
target HER2+ breast cancer.
PMID- 26442204
TI - Letter From the Chair.
PMID- 26442203
TI - The AQP2 mutation V71M causes nephrogenic diabetes insipidus in humans but does
not impair the function of a bacterial homolog.
AB - Several point mutations have been identified in human aquaporins, but their
effects on the function of the respective aquaporins are mostly enigmatic. We
analyzed the impact of the aquaporin 2 mutation V71M, which causes nephrogenic
diabetes insipidus in humans, on aquaporin structure and activity, using the
bacterial aquaglyceroporin GlpF as a model. Importantly, the sequence and
structure around the V71M mutation is highly conserved between aquaporin 2 and
GlpF. The V71M mutation neither impairs substrate flux nor oligomerization of the
aquaglyceroporin. Therefore, the human aquaporin 2 mutant V71M is most likely
active, but cellular trafficking is probably impaired.
PMID- 26442205
TI - The Use of a Pure Native Collagen Dressing for Wound Bed Preparation Prior to Use
of a Living Bi-layered Skin Substitute.
AB - Management of chronic wounds in the outpatient setting is quite challenging. The
extensive co-morbid medical problems of the chronically ill patient along with
the complexities of the wound bed and its biochemical environment has led to a
plethora of patients with poor wound healing. This ever increasing population is
a challenge for the wound care practitioner and cost to the health care system
and patient. Increased wound chronicity has promulgated the use of advanced wound
care products, including Living Skin Substitutes (LSS), in an attempt to obtain
wound closure, and ultimately both physiological and functional healing.(1-3) In
the outpatient setting, it is evident that the efficacy of the LSS varies widely
depending on the patient type with some patients responding quite favorably while
others who do not achieve healing despite repeated applications of LSS. This case
series demonstrates that a systematic method of wound bed preparation prior to
the application of LSS improved healing outcomes. The entire wound bed
preparation protocol included autolytic, non-selective, and sharp-selective
debridement, if deemed appropriate, followed by the weekly application of a pure
native collagen. The wound bed preparation protocol was completed prior to LSS
application. This case series presents evidence supporting the application of a
100% native collagen dressing to wound bed prior to the final step of LSS
utilization.
PMID- 26442206
TI - Clinical Effectiveness of Hyperbaric Oxygen Therapy in Complex Wounds.
AB - Hyperbaric Oxygen (HBO, HBO2) Therapy is a non-invasive therapy. It has been
applied as adjuvant treatment in many medical conditions over the past 50 years.
Different treatment protocols have been proven effective for specifically
indicated conditions. To evaluate the clinical effectiveness of Hyperbaric Oxygen
(HBO) Therapy as an adjunctive treatment for patients with complex wounds. In
this prospective cohort study, 40 patients with complex wounds were included. All
patients received HBO. HBO was delivered with 100% oxygen for 90 min at 2.0-2.4
ATA. Wound sizes were assessed by one wound surgeon before, during, and every 2
weeks for a total of 12 months after HBO. An analysis of demographic data, wound
size and wound photography was performed. Over the 22-month period ending October
31, 2013, 40 patients (21 men and 19 women) with a mean age of 59.73 (range, 29
88) with complex wounds were included. All complex wounds studied were at least 6
months old. The mean wound size was 16.72 cm(2) in diameter. Thirty-one patients
with complex wounds healed after the completion of a series of HBO treatments
(77.5%). Two orocutaneous fistulas were completely closed without further
surgery. After 5 HBO treatments, the wound size reduced by 29.7% on average (p =
1.24 * 10(-6)). After 10 HBO treatments, the wound size statistically
significantly reduced by an additional 16.9% (p = 0.0002). There were no
complications in this study. Wound healing process was accelerated by HBO.
Significant wound size reduction was noted after 5 HBO treatments. Because the
biggest reduction in wound size occurred within the first 10 HBO treatments, it
is important to conduct these first treatments without interruption. HBO is an
effective and safe treatment modality for complex wounds.
PMID- 26442207
TI - Optimizing Wound Bed Preparation With Collagenase Enzymatic Debridement.
AB - Difficult-to-heal and chronic wounds affect tens of millions of people worldwide.
In the U.S. alone, the direct cost for their treatment exceeds $25 billion. Yet
despite advances in wound research and treatment that have markedly improved
patient care, wound healing is often delayed for weeks or months. For venous and
diabetic ulcers, complete wound closure is achieved in as few as 25%-50% of
chronic or hard-to-heal wounds. Wound bed preparation and the consistent
application of appropriate and effective debridement techniques are recommended
for the optimized treatment of chronic wounds. The TIME paradigm (Tissue,
Inflammation/infection, Moisture balance and Edge of wound) provides a model to
remove barriers to healing and optimize the healing process. While we often think
of debridement as an episodic event that occurs in specific care giver/patient
interface. There is the possibility of a maintenance debridement in which the
chronic application of a medication can assist in both the macroscopic and
microscopic debridement of a wound. We review the various debridement therapies
available to clinicians in the United States, and explore the characteristics and
capabilities of clostridial collagenase ointment (CCO), a type of enzymatic
debridement, that potentially allows for epithelialization while debriding. It
appears that in the case of CCO it may exert this influences by removal of the
necrotic plug while promoting granulation and sustaining epithelialization. It is
also easily combined with other methods of debridement, is selective to necrotic
tissue, and has been safely used in various populations. We review the body of
evidence has indicated that this concept of maintenance debridement, especially
when combined episodic debridement may add a cost an efficacious, safe and cost
effective choice for debridement of cutaneous ulcers and burn wounds and it will
likely play an expanding role in all phases of wound bed preparation.
PMID- 26442208
TI - Calciphylaxis in Patients With Preserved Kidney Function.
AB - Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a
devastating disease typically seen in patients with end stage renal disease. It
manifests as extremely painful symmetrical wounds resistant to surgical and
medical interventions. The prevalence of CUA among hemodialysis dependent
patients was found to be as high as 4.1%. The management of patients with CUA
requires a multidisciplinary approach by the medical team, yet often results in a
low rate of successful outcomes. Recently, non-uremic calciphylaxis (NUC) has
been described in the absence of kidney disease. Limited knowledge exists on the
management of NUC and the outcomes of this condition. Herein we describe three
clinical scenarios of patients diagnosed with NUC in the absence of permanent or
prolonged acute renal pathology. The reporting of successful and fruitless
therapeutic interventions for wound management in NUC is important for compiling
the evidence of effective therapeutic strategies.
PMID- 26442210
TI - Editorial: Advances in Combination Tumor Immunotherapy.
PMID- 26442209
TI - Mechanical Stress as the Common Denominator between Chronic Inflammation, Cancer,
and Alzheimer's Disease.
AB - The pathogenesis of common diseases, such as Alzheimer's disease (AD) and cancer,
are currently poorly understood. Inflammation is a common risk factor for cancer
and AD. Recent data, provided by our group and from others, demonstrate that
increased pressure and inflammation are synonymous. There is a continuous
increase in pressure from inflammation to fibrosis and then cancer. This is in
line with the numerous papers reporting high interstitial pressure in cancer. But
most authors focus on the role of pressure in the lack of delivery of
chemotherapy in the center of the tumor. Pressure may also be a key factor in
carcinogenesis. Increased pressure is responsible for oncogene activation and
cytokine secretion. Accumulation of mechanical stress plays a key role in the
development of diseases of old age, such as cardiomyopathy, atherosclerosis, and
osteoarthritis. Growing evidence suggest also a possible link between mechanical
stress in the pathogenesis of AD. The aim of this review is to describe
environmental and endogenous mechanical factors possibly playing a pivotal role
in the mechanism of chronic inflammation, AD, and cancer.
PMID- 26442211
TI - Dosimetric Effects of the Interfraction Variations during Whole Breast
Radiotherapy: A Prospective Study.
AB - INTRODUCTION: The aim of this work was to assess the dosimetric impact of the
interfraction variations during breast radiotherapy. MATERIALS AND METHODS: Daily
portal imaging measurements were prospectively performed in 10 patients treated
with adjuvant whole breast irradiation (50 Gy/25 fractions). Margins between the
clinical target volume and the planning target volume (PTV) were 5 mm in the
three dimensions. Parameters of interest were the central lung distance (CLD) and
the inferior central margin (ICM). Daily movements were applied to the baseline
treatment planning (TP1) to design a further TP (TP2). The PTV coverage and organ
at risk exposure were measured on both TP1 and TP2, before being compared.
RESULTS: A total of 241 portal images were analyzed. The random and systematic
errors were 2.6 and 3.7 mm for the CLD, 4.3 and 6.9 mm for the ICM, respectively.
No significant consequence on the PTV treatments was observed (mean variations:
+0.1%, p = 0.56 and -1.8%, p = 0.08 for the breast and the tumor bed,
respectively). The ipsilateral lung and heart exposure was not significantly
modified. CONCLUSION: In our series, the daily interfraction variations had no
significant effect on the PTV coverage or healthy tissue exposure during breast
radiotherapy.
PMID- 26442213
TI - Use of a Flexible Inflatable Multi-Channel Applicator for Vaginal Brachytherapy
in the Management of Gynecologic Cancer.
AB - INTRODUCTION: Evaluate use of novel multi-channel applicator (MC) CapriTM to
improve vaginal disease coverage achievable by single-channel applicator (SC) and
comparable to Syed plan simulation. MATERIALS AND METHODS: Twenty-eight plans
were evaluated from four patients with primary or recurrent gynecologic cancer in
the vagina. Each received whole pelvis radiation, followed by three weekly
treatments using HDR brachytherapy with a 13-channel MC. Upper vagina was treated
to 5 mm depth to 1500 cGy/3 fractions with a simultaneous integrated boost
totaling 2100 cGy/3 fractions to tumor. Modeling of SC and Syed plans was
performed using MC scans for each patient. Dosimetry for MC and SC plans was
evaluated for PTV700 cGy coverage, maximum dose to 2 cm(3) to bladder, rectum, as
well as mucosal surface points. Dosimetry for Syed plans was calculated for
PTV700 cGy coverage. Patients were followed for treatment response and toxicity.
RESULTS: Dosimetric analysis between MC and SC plans demonstrated increased tumor
coverage (PTV700 cGy), with decreased rectal, bladder, and contralateral vaginal
mucosa dose in favor of MC. These differences were significant (p < 0.05).
Comparison of MC and Syed plans demonstrated increased tumor coverage in favor of
Syed plans which were not significant (p = 0.71). Patients treated with MC had no
cancer recurrence or >=grade 3 toxicity. CONCLUSION: Use of MC was efficacious
and safe, providing superior coverage of tumor volumes <=1 cm depth compared to
SC and comparable to Syed implant. MC avoids excess dose to surrounding organs
compared to SC, and potentially less morbidity than Syed implants. For tumors
extending <=1 cm depth, use of MC represents an alternative to an interstitial
implant.
PMID- 26442212
TI - Potential Gene Interactions in the Cell Cycles of Gametes, Zygotes, Embryonic
Stem Cells and the Development of Cancer.
AB - OBJECTIVES: This review is to explore whether potential gene interactions in the
cell cycles of gametes, zygotes, and embryonic stem (ES) cells are associated
with the development of cancer. METHODS: MEDPILOT at the Central Library of the
University of Cologne, Germany (Zentralbibliothek Koln) that covers 5,800
international medical journals and 4,300 E-journals was used to collect data. The
initial searches were done in December 2012 and additional searches in October
2013-May 2015. The search terms included "cancer development," "gene
interaction," and "ES cells," and the time period was between 1998 and 2015. A
total of 147 articles in English language only were included in this review.
RESULTS: Transgenerational gene translation is implemented in the zygote through
interactions of epigenetic isoforms of transcription factors (TFs) from parental
gametes, predominantly during the first two zygote cleavages. Pluripotent
transcription factors may provide interacting links with mutated genes during
zygote-to-ES cell switches. Translation of post-transcriptional carcinogenic
genes is implemented by abnormally spliced, tumor-specific isoforms of gene
encoded mRNA/non-coding RNA variants of TFs employing de novo gene synthesis and
neofunctionalization. Post-translationally, mutated genes are preserved in pre
neoplastic ES cell subpopulations that can give rise to overt cancer stem cells.
Thus, TFs operate as cell/disease-specific epigenetic messengers triggering
clinical expression of neoplasms. CONCLUSION: Potential gene interactions in the
cell cycle of gametes, zygotes, and ES cells may play some roles in the
development of cancer.
PMID- 26442214
TI - Inhibition of Immune Checkpoints and Vascular Endothelial Growth Factor as
Combination Therapy for Metastatic Melanoma: An Overview of Rationale,
Preclinical Evidence, and Initial Clinical Data.
AB - The role of angiogenesis as a mediator of immune regulation in the tumor
microenvironment has recently come into focus. Furthermore, emerging evidence
indicates that immunotherapy can lead to immune-mediated vasculopathy in the
tumor, suggesting that the tumor vasculature may be an important interface
between the tumor-directed immune response and the cancer itself. The advent of
immune checkpoint inhibition as an effective immunotherapeutic strategy for many
cancers has led to a better understanding of this interface. While the inhibition
of angiogenesis through targeting of vascular endothelial growth factor (VEGF)
has been used successfully for the treatment of cancer for many years, the
mechanisms of its anti-tumor activity remain poorly understood. Initial studies
of the complex relationship between angiogenesis, VEGF signaling and the immune
system suggest that the combination of immune checkpoint blockade with
angiogenesis inhibition has potential. While the majority of this work has been
performed in metastatic melanoma, immunotherapy is rapidly showing promise in a
broad range of malignancies and efforts to enhance immunotherapy will broadly
impact the future of oncology. Here, we review the preclinical rationale and
clinical investigations of combined angiogenesis inhibition and
immunotherapy/immune checkpoint inhibition as a potentially promising
combinatorial approach for cancer treatment.
PMID- 26442215
TI - Screening for Psychological Distress in Adult Primary Brain Tumor Patients and
Caregivers: Considerations for Cancer Care Coordination.
AB - INTRODUCTION: This study aimed to assess psychological distress (PD) as scored by
the Distress Thermometer (DT) in adult primary brain tumor patients and
caregivers (CGs) in a clinic setting and ascertain if any high-risk subgroups for
PD exist. MATERIAL AND METHODS: From May 2012 to August 2013, n = 96 patients and
n = 32 CG underwent DT screening at diagnosis, and a differing cohort of n = 12
patients and n = 14 CGs at first recurrence. Groups were described by diagnosis
(high grade, low grade, and benign) and English versus non English speaking.
Those with DT score >=4 met caseness criteria for referral to psycho-oncology
services. One-way ANOVA tests were conducted to test for between-group
differences where appropriate. RESULTS: At diagnosis and first recurrence, 37.5
and 75.0% (respectively) of patients had DT scores above the cutoff for distress.
At diagnosis, 78.1% of CGs met caseness criteria for distress. All CGs at
recurrence met distress criterion. Patients with high-grade glioma had
significantly higher scores than those with a benign tumor. For patients at
diagnosis, non English speaking participants did not report significantly higher
DT scores than English speaking participants. DISCUSSION: Psychological distress
is particularly elevated in CGs and in patients with high-grade glioma at
diagnosis. Effective PD screening, triage, and referral by skilled care
coordinators are vital to enable timely needs assessment, psychological support,
and effective intervention.
PMID- 26442216
TI - Preclinical Evaluation of Intraoperative Low-Energy Photon Radiotherapy Using
Spherical Applicators in Locally Advanced Prostate Cancer.
AB - BACKGROUND: Surgery plus adjuvant radiotherapy is standard care for locally
advanced prostate cancer (stage pT3R1). Intraoperative low-energy photon
radiotherapy offers several advantages over external beam radiotherapy, and
several systems are now available for its delivery, using spherical applicators,
which require only limited shielding. The aim of this study was to evaluate the
feasibility of this technique for the prostate bed. MATERIALS AND METHODS:
Applicators were assessed using MRI image data and cadaveric dissection. In
cadavers, targeted tissues, defined as a urethral section, both neurovascular
bundle sections, the bladder neck and the beds of the seminal vesicles, were
marked with metallic surgical clips. Distances between clips and applicator were
measured using CT. A dosimetric study of the application of 12 Gy at 5 mm depth
was performed using CT images of prostatectomized cadavers. RESULTS: Using MRI
images from 34 prostate cancer patients, we showed that the ideal applicator
diameter ranges from 45 to 70 mm. Using applicators of different sizes to
encompass the prostate bed in nine cadavers, we showed that the distance between
target tissues and applicator was <2 mm for all target tissues except the upper
extremity of the seminal vesicles (19 mm). Dosimetric study showed a good dose
distribution in all target tissues in contact with the applicator, with a low
probability of rectum and bladder complication. CONCLUSION: Intraoperative
radiotherapy of the prostate bed is feasible, with good coverage of targeted
tissues. Clinical study of safety and efficacy is now required.
PMID- 26442217
TI - Editorial: Advances in Epithelial Ovarian Cancer: Model Systems,
Microenvironmental Influences, Therapy, and Origins.
PMID- 26442218
TI - Resection Followed by Involved-Field Fractionated Radiotherapy in the Management
of Single Brain Metastasis.
AB - INTRODUCTION: We expanded upon our previous experience using involved-field
fractionated radiotherapy (IFRT) as an alternative to whole brain radiotherapy or
stereotactic radiosurgery for patients with surgically resected brain metastases
(BM). MATERIALS AND METHODS: All patients with single BM who underwent surgical
resection followed by IFRT at our institution from 2006 to 2013 were evaluated.
Local recurrence (LR)-free survival, distant failure (DF)-free survival, and
overall survival (OS) were determined. Analyses were performed associating
clinical variables with LR and DF. Salvage approaches and toxicity of treatment
for each patient were also assessed. RESULTS: Median follow-up was 19.1 months.
Fifty-six patients were treated with a median dose of 40.05 Gy/15 fractions with
IFRT to the resection cavity. LR-free survival was 91.4%, DF-free survival was
68.4%, and OS was 77.7% at 12 months. No variables were associated with increased
LR; however, melanoma histopathology and infratentorial location were associated
with DF on multivariate analysis. LRs were salvaged in 5/8 patients, and DFs were
salvaged in 24/29 patients. Two patients developed radionecrosis. CONCLUSION:
Adjuvant IFRT is feasible and safe for well-selected patients with surgically
resected single BM. Acceptable rates of local control and salvage of distal
intracranial recurrences continue to be achieved with continued follow-up.
PMID- 26442219
TI - Detection of Circulating Tumor Cells in Non-Small Cell Lung Cancer.
AB - Lung cancer is the most common cause of cancer-related deaths that frequently
metastasizes prior to disease diagnosis. Circulating tumor cells (CTCs) are found
in many different types of epithelial tumors and are of great clinical interest
in terms of prognosis and therapy intervention. Here, we present and discuss
epithelial cell adhesion molecule-dependent and -independent capture of CTCs in
non-small cell lung cancer (NSCLC) and the clinical relevance of CTC detection
and characterization. Taking blood samples and analyzing CTCs as "liquid biopsy"
might be a far less invasive diagnostic strategy than biopsies of lung tumors or
metastases. Moreover, sequential blood sampling allows to study the dynamic
changes of tumor cells during therapy, in particular the development of resistant
tumor cell clones.
PMID- 26442220
TI - Commentary: The unliganded glucocorticoid receptor positively regulates the tumor
suppressor gene BRCA1 through GABP beta.
PMID- 26442222
TI - Diabetes care among elderly medicare beneficiaries with Parkinson's disease and
diabetes.
AB - BACKGROUND: Elderly individuals with type 2 diabetes mellitus (T2DM) suffer from
several comorbidities, which affect their health outcomes, as well as process of
care. This study assessed process and intermediate clinical outcomes of diabetes
care among elderly individuals with T2DM and co-occurring Parkinson's
disease(PD). METHODS: This study used a retrospective cohort design with
propensity score matching using Humana Medicare Advantage Part D claims database
(2007-2011) and included elderly (age >= 65 years) Medicare beneficiaries with
T2DM (identified by ICD-9-CM code of 250.x0 or 250.x2). PD was identified using
ICD-9-CM code of 332.xx. After propensity score matching there were 2,703
individuals with T2DM and PD and 8,109 with T2DM and no PD. The three processes
of care measures used in this study included: (i) HbA1c test; (ii) Lipid test;
(iii) and Nephropathy screening. Intermediate clinical outcomes consisted of
glycemic and lipid control. RESULTS: Multivariable conditional logistic
regressions revealed that elderly individuals with T2DM and PD were 12 % (AOR:
0.88, 95 %CI: 0.79-0.97) and 18 % (AOR: 0.82, 95 %CI: 0.72-0.94) less likely to
meet the annual American Diabetes Association (ADA) recommended HbA1c and lipid
testing goals respectively compared to individuals with T2DM and no PD.
Multinomial conditional logistic regressions showed that elderly individuals with
T2DM and PD were more likely to have HbA1c and lipid (HbA1c < 8 %; LDL-C <100
mg/dl; HDL-C >= 50 mg/dl; triglyceride <150 mg/dl; and total cholesterol <200
mg/dl) control. CONCLUSIONS: Among elderly individuals with T2DM, those with PD
were less likely to achieve ADA recommended annual HbA1c and lipid testing
compared to those without PD. However, PD individuals were more likely to achieve
intermediate glycemic and lipid control.
PMID- 26442221
TI - The trans-Golgi SNARE syntaxin 10 is required for optimal development of
Chlamydia trachomatis.
AB - Chlamydia trachomatis, an obligate intracellular pathogen, grows inside of a
vacuole, termed the inclusion. Within the inclusion, the organisms differentiate
from the infectious elementary body (EB) into the reticulate body (RB). The RB
communicates with the host cell through the inclusion membrane to obtain the
nutrients necessary to divide, thus expanding the chlamydial population. At late
time points within the developmental cycle, the RBs respond to unknown molecular
signals to redifferentiate into infectious EBs to perpetuate the infection cycle.
One strategy for Chlamydia to obtain necessary nutrients and metabolites from the
host is to intercept host vesicular trafficking pathways. In this study we
demonstrate that a trans-Golgi soluble N-ethylmaleimide-sensitive factor
attachment protein (SNARE), syntaxin 10, and/or syntaxin 10-associated Golgi
elements colocalize with the chlamydial inclusion. We hypothesized that Chlamydia
utilizes the molecular machinery of syntaxin 10 at the inclusion membrane to
intercept specific vesicular trafficking pathways in order to create and maintain
an optimal intra-inclusion environment. To test this hypothesis, we used siRNA
knockdown of syntaxin 10 to examine the impact of the loss of syntaxin 10 on
chlamydial growth and development. Our results demonstrate that loss of syntaxin
10 leads to defects in normal chlamydial maturation including: variable inclusion
size with fewer chlamydial organisms per inclusion, fewer infectious progeny, and
delayed or halted RB-EB differentiation. These defects in chlamydial development
correlate with an overabundance of NBD-lipid retained by inclusions cultured in
syntaxin 10 knockdown cells. Overall, loss of syntaxin 10 at the inclusion
membrane negatively affects Chlamydia. Understanding host machinery involved in
maintaining an optimal inclusion environment to support chlamydial growth and
development is critical toward understanding the molecular signals involved in
successful progression through the chlamydial developmental cycle.
PMID- 26442223
TI - Assessment of the feasibility of using sunlight exposure to obtain the
recommended level of vitamin D in Canada.
AB - BACKGROUND: Endogenous vitamin D synthesis can be affected by a number of
variables, including skin colour, amount of skin exposed and levels of
ultraviolet radiation. The objective of this study was to assess the feasibility
of using only sunlight exposure in Canada to meet the daily recommended level of
vitamin D, given differences in these variables and adherence to guidelines for
sun protection. METHODS: Ultraviolet index data for 13 Canadian sites were
obtained from Environment Canada. The sun exposure times required to synthesize
1000 IU of vitamin D in fair- and dark-skinned people who exposed either 1/4 or
1/8 of their body surface area to the sun were calculated for each hour of the
year. These times were then classified according to whether the ultraviolet index
was 3 or more (when sun protection is advised) or less than 3. RESULTS: During
the fall and winter months and in the more northern sites, ultraviolet radiation
levels were too low for all skin types to use sun exposure alone to obtain enough
vitamin D within one time period. The required exposure time became longer when a
smaller surface area was exposed. For people with darker skin, it can be
difficult even in the summer to find opportunities outside of when sun protection
is advised to use sunlight to obtain the recommended dose of vitamin D.
INTERPRETATION: Although sun exposure is an important source of vitamin D,
Canadians should look to other safe sources to meet the body's vitamin D
requirements throughout the year.
PMID- 26442224
TI - Prevalence and management of osteoarthritis in primary care: an epidemiologic
cohort study from the Canadian Primary Care Sentinel Surveillance Network.
AB - BACKGROUND: Osteoarthritis is a common chronic condition that affects many older
Canadians and is a considerable cause of disability. Our objective was to
describe the epidemiology of osteoarthritis in patients aged 30 years and older
using electronic medical records (EMRs) in a Canadian primary care population.
METHODS: In this retrospective cohort study, we analyzed the EMRs of 207 610
patients over 30 years of age (extracted on December 31, 2012) who had at least
one clinic visit during the preceding 2 years. We calculated the age-sex
standardized prevalence of diagnosed osteoarthritis and its association with
comorbidities and covariates available in the Canadian Primary Care Sentinel
Surveillance Network database. RESULTS: The estimated prevalence of diagnosed
osteoarthritis was 14.2% (15.6% among women, 12.4% among men). The diagnosis of
osteoarthritis was associated with several comorbidities: hypertension
(prevalence ratio [PR] 1.17, 95% confidence interval [CI] 1.15-1.18), depression
(PR 1.26, 95% CI 1.22-1.3), chronic obstructive pulmonary disease (COPD) (PR
1.16, 95% CI 1.11-1.21) and epilepsy (PR 1.27, 95% CI 1.13-1.43). In addition,
56.6% of patients had received a prescription for a range of nonsteroidal anti
inflammatory drugs, 45% of which were topical. Opioid medications were prescribed
to 33% of patients for pain management. CONCLUSION: Osteoarthritis is a common
disease in middle-aged and older Canadians. It is more common in women than in
men and is associated with comorbid conditions. Most patients with osteoarthritis
received pharmacotherapy for inflammation and pain management. As the Canadian
population ages, osteoarthritis will become an increasing burden for individuals
and the health care system.
PMID- 26442225
TI - Incidence and cohort prevalence for autism spectrum disorders in the Avalon
Peninsula, Newfoundland and Labrador.
AB - BACKGROUND: Recent studies have reported increased prevalence for autism spectrum
disorders in a number of geographical locations. Our objective was to determine
the incidence and 1-year cohort prevalence for autism spectrum disorders in
children less than 15 years of age and living in the Avalon Peninsula at the time
of diagnosis. METHODS: Retrospective and prospective data were obtained from the
Janeway Children's Health and Rehabilitation Centre (St. John's), including the
identification and specific diagnosis for all children assessed for autism
spectrum disorder from 2006 to 2010. Additional clinic data were reviewed to
update the data until the end of 2013. RESULTS: From 2006 to 2010, 272 children
had a diagnosis of autism spectrum disorder, averaging 54 new cases per year. The
incidence of new cases increased from 10.1 to 16.7 cases per 10 000 per year from
2006 to 2010. At the end of 2013, the prevalence among children born in 2006 was
1 case of autism spectrum disorder per 46 children or 215.77 per 10 000.
INTERPRETATION: We found higher rates of autism spectrum disorder than previously
reported for this population. The prevalence in this region is also high when
compared with other global populations. The high rate of diagnosis supports the
need for a provincial autism spectrum disorder registry and further research on
autism spectrum disorder within this population.
PMID- 26442226
TI - A review of specialties performing temporal artery biopsies in Ontario: a
retrospective cohort study.
AB - BACKGROUND: Temporal artery biopsy is the gold standard for the diagnosis of
giant cell arteritis, but the numbers and types of surgical specialists
performing temporal artery biopsies are unknown. The goal of this study was to
determine which surgical specialists performed temporal artery biopsies and how
geographic location influenced this trend over a period of 10 years. METHODS:
This retrospective cohort study included all physicians practising in Ontario
from 2002 to 2013. Using comprehensive physician services data from the
IntelliHEALTH Medical Services database, physicians performing temporal artery
biopsies were identified by the Ontario Health Insurance Plan billing code
submitted for remuneration. Physicians were categorized by specialty and
geographic Local Health Integration Unit. RESULTS: A total of 9958 patients
underwent a temporal artery biopsy during the study period: the biopsies were
performed by 11 different subspecialties. The number of patients undergoing a
temporal artery biopsy declined over the 10-year study period. Most procedures
were performed by general surgeons (38.1%), followed by ophthalmologists (31.0%)
and plastic surgeons (23.6%). Ophthalmologists performed more temporal artery
biopsies per person compared with general surgeons, but significantly more
general surgeons performed at least 1 biopsy. There was significant variation
based on geographic location: plastic surgeons performed the most biopsies in
regions with a population of more than 1 million people, and general surgeons
performed most of the biopsies in rural areas. INTERPRETATION: Geographic
location heavily influenced which specialty was most likely to perform temporal
artery biopsies. General surgery, ophthalmology and plastic surgery emerged as
leaders in this area, and their residency programs should include formal training
in this procedure in their curricula.
PMID- 26442227
TI - Postmarket safety of drugs approved by Health Canada on the basis of clinical and
surrogate outcomes: a cohort study.
AB - BACKGROUND: Health Canada approves drugs on the basis of evidence from clinical
trials using clinical or surrogate outcomes. This study compares the postmarket
safety of these 2 groups of drugs. METHODS: Information about whether clinical or
surrogate outcomes were used and the date of market approval were obtained from
Health Canada's Summary Basis of Decision documents issued from Jan. 1, 2005, to
Dec. 31, 2014. Safety warnings and the dates they were issued were identified
through advisories on the MedEffect Canada website. Kaplan-Meier survival curves
were calculated to determine the likelihood that drugs in the clinical and
surrogate outcome groups would receive a serious safety warning. The time from
market authorization to first serious safety warning was compared for the 2
groups of drugs. RESULTS: A total of 124 drugs were approved by Health Canada
using clinical outcomes and 114 using surrogate outcomes. Kaplan-Meier curves did
not differ between the 2 groups (p < 0.9). The median time from market
authorization to first serious safety warning was 722 days in the clinical
outcome group and 818 days in the surrogate outcome group (difference 96 days,
95% confidence interval -295 to 425). INTERPRETATION: We found no statistically
significant difference in postmarket safety between drugs approved using clinical
outcomes and those approved using surrogate outcomes. Because drugs in the
surrogate outcome group are approved before their benefit:harm ratio is fully
established, these drugs should be used with caution until their clinical
benefits are better understood.
PMID- 26442229
TI - The experience of nursing women with breastfeeding support: a qualitative
inquiry.
AB - BACKGROUND: Breastfeeding difficulties are a common occurrence, are highly
personal and can vary from one infant to the next for any mother. Multiple
sources of support, help and advice for breastfeeding are available to nursing
mothers. Evidence suggests that the experience of the quality of breastfeeding
supports may play an important role in maternal mental health and well-being in
the postpartum period. We sought to explore the experiences of nursing mothers
with support they received for breastfeeding in order to better inform and
optimize existing breastfeeding supports and interventions. METHODS: We conducted
a qualitative inquiry of nursing mothers' experiences with help, advice and
support for breastfeeding. Participants were asked to provide open-ended, written
accounts of their experiences with all sources of breastfeeding support received
in the 6 months following the delivery of a healthy full-term infant in Calgary.
We conducted qualitative thematic analysis, using constant comparison techniques.
RESULTS: The sample included 86 mothers. Our analyses uncovered 4 emergent themes
that contributed to the perceived quality of breastfeeding support: knowledge,
effectiveness, sensitivity/emotional support and accessible when sought.
INTERPRETATION: Our study provides a greater understanding of how mothers
perceive the quality of the breastfeeding support that they receive, as well as
what qualities of breastfeeding support are seen as beneficial or negative. The
qualities contributing to the perception of breastfeeding support are important
to inform and optimize perinatal care, and potentially reduce the risk of
negative mental health outcomes for mothers.
PMID- 26442228
TI - Identification of the physician workforce providing palliative care in Ontario
using administrative claims data.
AB - BACKGROUND: Little is known about the physician workforce providing palliative
care in Canada, and in Ontario specifically. We developed an algorithm to
identify palliative care physicians using administrative claims data and
validated it against a reference sample. We then applied the algorithm to all
general practitioners/family physicians (GP/FPs) in the province of Ontario to
describe and quantify those identified by the algorithm. METHODS: W e reviewed
Ontario Health Insurance Plan claims from Jan. 1, 2008, to Dec. 31, 2011, to
determine each physician's proportion of claims that were for palliative care. We
empirically selected a data-driven cut-off, whereby physicians whose proportion
of palliative care claims was above the threshold were defined as palliative care
physicians. We validated the cut-off against a reference sample of physicians who
self-identified as providing mostly palliative care in a study-specific survey.
We then applied this algorithm to all GP/FPs in the province. RESULTS: We
empirically selected 10% as the cut-off for the proportion of palliative care
claims. This threshold had exceptional specificity and positive predictive value
(97.8% and 90.5%, respectively) and adequate sensitivity (76.0%) when compared
with the reference sample (n = 118). When applied to all GP/FPs in the province,
the algorithm identified 276 practising mostly palliative care. Of these, 135
(48.9%) were women, 265 (96.0%) practised in urban locations, and 145 (52.5%)
worked part time. INTERPRETATION: Our algorithm readily identified and quantified
the workforce of palliative care physicians in Ontario. Such a tool has numerous
applications for both health service planners and researchers.
PMID- 26442230
TI - Regional variation in the use of surgery in Ontario.
AB - BACKGROUND: Regional variation in the use of surgery implies that there is
uncertainty regarding appropriate use. The objectives of this study were to
identify which surgical procedures are most commonly performed in the province of
Ontario and measure the extent of variation in the use of surgical procedures
across Ontario counties. METHODS: We used the Canadian Institute for Health
Information Discharge Abstract Database, Same Day Surgery Database and National
Ambulatory Care Reporting System to retrieve information on all inpatient and day
surgery visits in Ontario between Apr. 1, 2002, and Mar. 31, 2011. We identified
the 84 most common procedures according to Canadian Classification of
Interventions codes. We calculated rates of use for each procedure throughout the
49 Ontario counties and then calculated measures of variation (quartile ratio and
systematic component of variation) in use between the counties. RESULTS:
Colonoscopy was the most commonly performed procedure during the study period,
with an average adjusted rate of 2012 per 100 000 population. The procedure with
the highest measure of variation was iridectomy, with a quartile ratio of 6.7,
followed by colposcopy (5.2), cervical biopsy (4.2) and femoral arteriography
(4.1). These procedures were less commonly performed. Common procedures such as
colonoscopy, cataract extraction and vaginal delivery had lower quartile ratios.
Analysis using the systematic component of variation as the measure of variation
gave similar results. INTERPRETATION: Colonoscopy was the most commonly performed
procedure in Ontario, and cataract extraction was the most common surgical
procedure. Procedures with the highest measures of variation between counties
tended to be those that occurred less commonly in Ontario, and common procedures
were associated with less regional variation.
PMID- 26442231
TI - Characteristics of patients receiving long-term opioid therapy for chronic
noncancer pain: a cross-sectional survey of patients attending the Pain
Management Centre at Hamilton General Hospital, Hamilton, Ontario.
AB - BACKGROUND: Characteristics of patients receiving long-term opioid therapy (>= 6
months) for chronic noncancer pain are poorly understood. We conducted a cross
sectional survey of this patient population to explore demographic variables,
pain relief, functional improvement, adverse effects and impressions of an
educational pamphlet on long-term opioid therapy. METHODS: We invited 260 adult
patients presenting to the Pain Management Centre at the Hamilton General
Hospital, Hamilton, Ontario, with chronic noncancer pain to complete a 20-item
survey. Patients who presented for procedures were not eligible for our study. We
used adjusted logistic regression models to explore the association between
higher morphine equivalent dose and pain relief, functional improvement, adverse
events and employment. RESULTS: The survey was completed by 170 patients (a
response rate of 65.4%). Most respondents (87.6%; 149 out of 170) were receiving
long-term opioid therapy, and the median morphine equivalent dose was 180 mg
daily (interquartile range 60-501). Most respondents reported at least modest (>
40%) opioid-specific pain relief (74.1%; 106 out of 143) and functional
improvement (67.6%; 96 out of 142), and 46.5% (66 out of 142) reported
troublesome adverse effects that they attributed to their opioid use. Most
patients were receiving disability benefits (68.3%; 99 out of 145) and, among
those respondents who were less than 65 years of age (90.3%; 131 out of 145), 10
(7.6%) were working full-time and 14 (10.7%) part-time. In our adjusted analyses,
higher morphine equivalent dose was associated with greater self-reported
functional improvement (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.07
1.96) but not with pain relief (OR 1.38, 95% CI 1.00-1.89), troublesome adverse
effects (OR 0.92, 95% CI 0.70-1.20) or employment (OR 0.80, 95% CI 0.56-1.15).
INTERPRETATION: Most outpatients receiving long-term opioid therapy for chronic
noncancer pain at a tertiary care chronic pain clinic reported at least moderate
pain relief and functional improvement; however, adverse effects were common and
few patients were engaged in competitive employment.
PMID- 26442232
TI - Patient and operational factors affecting wait times in a bariatric surgery
program in Toronto: a retrospective cohort study.
AB - BACKGROUND: Increasing rates of obesity have led to growing demand for bariatric
surgery. This has implications for wait times, particularly in publicly funded
programs. This study examined the impact of patient and operational factors on
wait times in a multidisciplinary bariatric surgery program. METHODS: A
retrospective study was conducted involving patients who were referred to a
tertiary care centre (University Health Network, Toronto Western Hospital,
Toronto) for bariatric surgery between June 2008 and July 2011. Patient
characteristics, dates of clinical assessments and records describing operational
changes were collected. Univariable analysis and multivariable log-linear and
parametric time-to-event regressions were performed to determine whether patient
and operational covariates were associated with the wait time for bariatric
surgery (i.e., length of preoperative evaluation). RESULTS: Of the 1664 patients
included in the analysis, 724 underwent surgery with a mean wait time of 440
(standard deviation 198) days and a median wait time of 445 (interquartile range
298-533) days. Wait times ranged from 3 months to 4 years. Univariable and
multivariable analyses showed that patients with active substance use (beta =
0.3482, p = 0.02) and individuals who entered the program in more recent
operational periods (beta = 0.2028, p < 0.001) had longer wait times.
Additionally, the median time-to-surgery increased over 3 discrete operational
periods (characterized by specific program changes related to scheduling and
staffing levels, and varying referral rates and defined surgical targets; p <
0.001). INTERPRETATION: Some patients could be identified at referral as being at
risk for longer wait times. We also found that previous operational decisions
significantly increased the wait time in the program since its inception.
Therefore, careful consideration must be devoted to process-level decision-making
for multistage bariatric surgical programs, because managerial and procedural
changes can affect timely access to treatment.
PMID- 26442233
TI - In utero Head Circumference is Associated with Childhood Allergy.
AB - BACKGROUND: Altered fetal growth is known to be associated with allergic disease.
Specifically, increased head circumference at birth has been linked to asthma and
elevated IgE. However, few studies have examined a link between early fetal
anthropometry and allergic disease. The aim of this study was to examine head
circumference at mid-gestation in children diagnosed with allergy. METHODS: This
was a retrospective cohort study, comprising pregnancies delivered between
10/2006 and 9/2010 at Nepean Hospital, Australia. Exclusion criteria were illegal
drug use, alcohol consumption, gestation <35 weeks, and gestational hypertension.
Pregnancy data were sourced from the Nepean Obstetric Database. Atopic diseases
(asthma, atopic dermatitis, and IgE-mediated food allergy) were assessed by
questionnaire at age 1-5 years. Infants from pregnancies with completed
questionnaires, who also had a mid-gestation ultrasound scan, were included (N =
121). Multiple logistic regression techniques were used to model head
circumference against the development of allergies. RESULTS: Smaller head
circumference at mid-gestation was associated with increased odds of allergic
disease in children aged 1-5 years. A 1 mm smaller head circumference was
associated with a 7% increased chance of allergies being later diagnosed,
adjusted for gestation (95% CI: 1-14%, p = 0.036). Head circumference at mid
gestation was also inversely correlated with the presence of multiple atopic
disease. CONCLUSION: Smaller mid-gestational head circumference is associated
with early childhood allergic disease, which suggests that fetal programing of
allergic disease occurs before mid-gestation. This suggests that mediators such
as brain-derived neurotrophic factor may be dysregulated early in utero in a
milieu, which also predisposes to atopic disease.
PMID- 26442234
TI - Myofascial Structural Integration Therapy on Gross Motor Function and Gait of
Young Children with Spastic Cerebral Palsy: A Randomized Controlled Trial.
AB - Though the cause of motor abnormalities in cerebral palsy is injury to the brain,
structural changes in muscle and fascia may add to stiffness and reduced
function. This study examined whether myofascial structural integration therapy,
a complementary treatment that manipulates muscle and fascia, would improve gross
motor function and gait in children <4 years with cerebral palsy. Participants (N
= 29) were enrolled in a randomized controlled trial (NCT01815814,
https://goo.gl/TGxvwd) or Open Label Extension. The main outcome was the Gross
Motor Function Measure-66 assessed at 3-month intervals. Gait (n = 8) was
assessed using the GAITRite((r)) electronic walkway. Parents completed a survey
at study conclusion. Comparing Treatment (n = 15) and Waitlist-Control groups (n
= 9), we found a significant main effect of time but no effect of group or time *
group interaction. The pooled sample (n = 27) showed a main effect of time, but
no significantly greater change after treatment than between other assessments.
Foot length on the affected side increased significantly after treatment, likely
indicating improvement in the children's ability to approach a heel strike.
Parent surveys indicated satisfaction and improvements in the children's quality
of movement. MSI did not increase the rate of motor skill development, but was
associated with improvement in gait quality.
PMID- 26442235
TI - Editorial: Univentricular Heart.
PMID- 26442236
TI - Work-Life Balance is an Illusion: Replace Guilt with Acceptance.
PMID- 26442237
TI - Sarcoidosis with Arteriovenous Malformation in a 15-Year-Old Girl - The Rarest of
the Rare.
AB - INTRODUCTION: Sarcoidosis is an uncommon multi-system disorder with many possible
complications. Arteriovenous malformations (AVMs) are a rare vascular
complication of sarcoidosis. CASE DESCRIPTION: A 15-year-old girl presented to
the Pediatric Clinic at AKUH with pulmonary, hepatic, joint, and skin
manifestations. Physical examination and investigations pointed toward
sarcoidosis, including raised erythrocyte sedimentation rate, angiotensin
converting enzyme (ACE), and alanine transaminase (ALT). An incidental finding of
pulmonary arteriovenous malformation (PAVM) was noticed on echocardiography. She
responded to oral corticosteroids, her ACE and ALT levels improved. There was
lack of indication for pulmonary angio-embolization for her PAVM. On a 3-year
follow-up, her condition improved and she is clinically well. DISCUSSION:
Pulmonary arteriovenous malformation is an extremely rare complication of
sarcoidosis, especially among the pediatric population. Hence, this is the first
reported case of its kind. The relation between sarcoidosis and PAVM is difficult
to establish; however, there are some theories. This condition may be treated
depending on the symptoms. Since our patient did not have any significant
symptoms of PAVM, she was treated for the underlying disease, i.e., sarcoidosis.
CONCLUSION: While dealing with patients having multi-system disorders like
sarcoidosis, one must be very vigilant so as not to miss out on any complication.
Regular follow-up visits should be scheduled to rule out new complications and to
monitor the past ones.
PMID- 26442238
TI - The Evidence-Based Approach to Adult-Onset Idiopathic Nephrotic Syndrome.
AB - Adult-onset nephrotic syndrome (NS) differs from its pediatric counterpart in
several important ways. Most importantly, NS in adults is more etiologically
heterogeneous compared to children, and thus treatment approaches rely heavily on
the histological diagnosis provided by renal biopsy. The evidence-based approach
to treatment of adult NS has been critically examined by the Kidney Disease
Improving Global Outcomes (KDIGO) guidelines in glomerulonephritis, published in
2012. Here, we examine the strengths and limits of those guidelines and review
recent work that expands the evidence-based approach.
PMID- 26442239
TI - Agenda Setting and Evidence in Maternal Health: Connecting Research and Policy in
Timor-Leste.
AB - The evidence-based policy (EBP) movement has received significant attention in
the scientific literature; however, there is still very little empirical research
to provide insight into how policy decisions are made and how evidence is used.
The lack of research on this topic in low- and middle-income countries is of
particular note. We examine the maternity waiting home policy in Timor-Leste to
understand the role of context, policy characteristics, individual actors, and
how evidence is used to influence the policy agenda. The research tracked the
maternity waiting home policy from 2005 to 2009 and is based on in-depth
interviews with 31 senior policy-makers, department managers, non-government
organization representatives, and United Nations advisors. It is also informed by
direct observation, attendance at meetings and workshops, and analysis of policy
documents. The findings from this ethnographic case study demonstrate that
although the post-conflict context opened up space for new policy ideas senior
Ministry of Health officials rather than donors had the most power in setting the
policy agenda. Maternity waiting homes were appealing because they were a
visible, non-controversial, and logical solution to the problem of accessing
maternal health services. Evidence was used in a variety of ways, from supporting
pre-determined agendas to informing new policy directions. In the pursuit of EBP,
we conclude that the power of research to inform policy lies in its timeliness
and relevance, and is facilitated by the connection between researchers and
policy-makers.
PMID- 26442240
TI - Budget Impact of Publicly Reimbursed Prescription Medicines in the Republic of
Srpska.
PMID- 26442241
TI - Review of Current International Decision-Making Processes for Newborn Screening:
Lessons for Australia.
AB - Newborn bloodspot screening has been operating successfully in Australia for
almost 50 years. Recently, the development of new technologies and treatments has
led to calls for the addition of new conditions to the screening programs.
Internationally, it is recognized by governments that national policies for
newborn screening should support transparent and evidence-based decision making,
and promote consistency between states within a country. Australia is lagging
behind the international community, and currently has no national policies or
decision-making processes, agreed by government, to support its newborn screening
programs. In contrast, New Zealand (NZ), the United Kingdom (UK), and the United
States of America (US) have robust and transparent processes to assess conditions
for screening, which have been developed by, and have pathways to, government.
This review provides detail on the current policy environment for newborn
screening in Australia, highlighting that there are a number of risks to the
programs resulting from the lack of a decision-making process. It also describes
the processes used to assess conditions for newborn screening in the US, UK, and
NZ. These examples highlight the benefits of developing a national decision
making process, including ensuring that screening is evidence based and
effective. These examples also provide models that might be considered for
Australia, as well as other countries currently seeking to introduce or expand
newborn bloodspot screening.
PMID- 26442242
TI - Disruptive Innovation Can Prevent the Next Pandemic.
AB - Public health surveillance (PHS) is at a tipping point, where the application of
novel processes, technologies, and tools promise to vastly improve efficiency and
effectiveness. Yet twentieth century, entrenched ideology and lack of training
results in slow uptake and resistance to change. The term disruptive innovation -
used to describe advances in technology and processes that change existing
markets - is useful to describe the transformation of PHS. Past disruptive
innovations used in PHS, such as distance learning, the smart phone, and field
based laboratory testing have outpaced older services, practices, and
technologies used in the traditional classroom, governmental offices, and
personal communication, respectively. Arguably, the greatest of these is the
Internet - an infrastructural innovation that continues to enable exponential
benefits in seemingly limitless ways. Considering the Global Health Security
Agenda and facing emerging and reemerging infectious disease threats, evolving
environmental and behavioral risks, and ever changing epidemiologic trends, PHS
must transform. Embracing disruptive innovation in the structures and processes
of PHS can be unpredictable. However, it is necessary to strengthen and unlock
the potential to prevent, detect, and respond.
PMID- 26442243
TI - Anxiety in the Elderly Can be a Vestibular Problem.
PMID- 26442244
TI - Relationship between the Quality of Service Provided through Store-and-Forward
Telemedicine Consultations and the Difficulty of the Cases - Implications for
Long-Term Quality Assurance.
AB - We examined the difficulty of telemedicine cases and the quality of the resultant
consultation in a mature store-and-forward telemedicine network. A random sample
of 10 telemedicine cases was selected from those occurring over a 3-month period
(5% of the workload) and they were scored by three experienced observers. Inter
observer agreement on the difficulty scores was poor (Fleiss's kappa = 0.18) and
it was also poor on the consultation quality scores (Fleiss's kappa = 0.11).
Differences between observers were minimized by consensus scoring, and the cases
were re-assessed jointly by two observers. Based on the consensus scores, there
was a weak negative relation between output quality and case difficulty, i.e.,
the more difficult cases tended to result in lower quality consultations.
However, the effect was non-significant (P = 0.59) and a larger study might be
helpful. In the meantime, routine monitoring of telemedicine service quality will
continue in the interests of quality assurance. As yet, there is no evidence on
which to base a correction for case difficulty.
PMID- 26442245
TI - Improving Speaker Recognition by Biometric Voice Deconstruction.
AB - Person identification, especially in critical environments, has always been a
subject of great interest. However, it has gained a new dimension in a world
threatened by a new kind of terrorism that uses social networks (e.g., YouTube)
to broadcast its message. In this new scenario, classical identification methods
(such as fingerprints or face recognition) have been forcedly replaced by
alternative biometric characteristics such as voice, as sometimes this is the
only feature available. The present study benefits from the advances achieved
during last years in understanding and modeling voice production. The paper
hypothesizes that a gender-dependent characterization of speakers combined with
the use of a set of features derived from the components, resulting from the
deconstruction of the voice into its glottal source and vocal tract estimates,
will enhance recognition rates when compared to classical approaches. A general
description about the main hypothesis and the methodology followed to extract the
gender-dependent extended biometric parameters is given. Experimental validation
is carried out both on a highly controlled acoustic condition database, and on a
mobile phone network recorded under non-controlled acoustic conditions.
PMID- 26442246
TI - Joint Analysis of Dependent Features within Compound Spectra Can Improve
Detection of Differential Features.
AB - Mass spectrometry is an important analytical technology in metabolomics. After
the initial feature detection and alignment steps, the raw data processing
results in a high-dimensional data matrix of mass spectral features, which is
then subjected to further statistical analysis. Univariate tests like Student's t
test and Analysis of Variances (ANOVA) are hypothesis tests, which aim to detect
differences between two or more sample classes, e.g., wildtype-mutant or between
different doses of treatments. In both cases, one of the underlying assumptions
is the independence between metabolic features. However, in mass spectrometry, a
single metabolite usually gives rise to several mass spectral features, which are
observed together and show a common behavior. This paper suggests to group the
related features of metabolites with CAMERA into compound spectra, and then to
use a multivariate statistical method to test whether a compound spectrum (and
thus the actual metabolite) is differential between two sample classes. The
multivariate method is first demonstrated with an analysis between wild-type and
an over-expression line of the model plant Arabidopsis thaliana. For a
quantitative evaluation data sets with a simulated known effect between two
sample classes were analyzed. The spectra-wise analysis showed better detection
results for all simulated effects.
PMID- 26442247
TI - Approximating Attractors of Boolean Networks by Iterative CTL Model Checking.
AB - This paper introduces the notion of approximating asynchronous attractors of
Boolean networks by minimal trap spaces. We define three criteria for determining
the quality of an approximation: "faithfulness" which requires that the
oscillating variables of all attractors in a trap space correspond to their
dimensions, "univocality" which requires that there is a unique attractor in each
trap space, and "completeness" which requires that there are no attractors
outside of a given set of trap spaces. Each is a reachability property for which
we give equivalent model checking queries. Whereas faithfulness and univocality
can be decided by model checking the corresponding subnetworks, the naive query
for completeness must be evaluated on the full state space. Our main result is an
alternative approach which is based on the iterative refinement of an initially
poor approximation. The algorithm detects so-called autonomous sets in the
interaction graph, variables that contain all their regulators, and considers
their intersection and extension in order to perform model checking on the
smallest possible state spaces. A benchmark, in which we apply the algorithm to
18 published Boolean networks, is given. In each case, the minimal trap spaces
are faithful, univocal, and complete, which suggests that they are in general
good approximations for the asymptotics of Boolean networks.
PMID- 26442248
TI - High-Resolution X-Ray Techniques as New Tool to Investigate the 3D
Vascularization of Engineered-Bone Tissue.
AB - The understanding of structure-function relationships in normal and pathologic
mammalian tissues is at the basis of a tissue engineering (TE) approach for the
development of biological substitutes to restore or improve tissue function. In
this framework, it is interesting to investigate engineered bone tissue, formed
when porous ceramic constructs are loaded with bone marrow stromal cells (BMSC)
and implanted in vivo. To monitor the relation between bone formation and
vascularization, it is important to achieve a detailed imaging and a quantitative
description of the complete three-dimensional vascular network in such
constructs. Here, we used synchrotron X-ray phase-contrast micro-tomography to
visualize and analyze the three-dimensional micro-vascular networks in bone
engineered constructs, in an ectopic bone formation mouse-model. We compared
samples seeded and not seeded with BMSC, as well as samples differently stained
or unstained. Thanks to the high quality of the images, we investigated the 3D
distribution of both vessels and collagen matrix and we obtained quantitative
information for all different samples. We propose our approach as a tool for
quantitative studies of angiogenesis in TE and for any pre-clinical investigation
where a quantitative analysis of the vascular network is required.
PMID- 26442250
TI - Underpinning Starch Biology with in vitro Studies on Carbohydrate-Active Enzymes
and Biosynthetic Glycomaterials.
AB - Starch makes up more than half of the calories in the human diet and is also a
valuable bulk commodity that is used across the food, brewing and distilling,
medicines and renewable materials sectors. Despite its importance, our
understanding of how plants make starch, and what controls the deposition of this
insoluble, polymeric, liquid crystalline material, remains rather limited.
Advances are hampered by the challenges inherent in analyzing enzymes that
operate across the solid-liquid interface. Glyconanotechnology, in the form of
glucan-coated sensor chips and metal nanoparticles, present novel opportunities
to address this problem. Herein, we review recent developments aimed at the
bottom-up generation and self-assembly of starch-like materials, in order to
better understand which enzymes are required for starch granule biogenesis and
metabolism.
PMID- 26442249
TI - Analytics for Metabolic Engineering.
AB - Realizing the promise of metabolic engineering has been slowed by challenges
related to moving beyond proof-of-concept examples to robust and economically
viable systems. Key to advancing metabolic engineering beyond trial-and-error
research is access to parts with well-defined performance metrics that can be
readily applied in vastly different contexts with predictable effects. As the
field now stands, research depends greatly on analytical tools that assay target
molecules, transcripts, proteins, and metabolites across different hosts and
pathways. Screening technologies yield specific information for many thousands of
strain variants, while deep omics analysis provides a systems-level view of the
cell factory. Efforts focused on a combination of these analyses yield
quantitative information of dynamic processes between parts and the host chassis
that drive the next engineering steps. Overall, the data generated from these
types of assays aid better decision-making at the design and strain construction
stages to speed progress in metabolic engineering research.
PMID- 26442251
TI - Biomechanics of Pediatric Manual Wheelchair Mobility.
AB - Currently, there is limited research of the biomechanics of pediatric manual
wheelchair mobility. Specifically, the biomechanics of functional tasks and their
relationship to joint pain and health is not well understood. To contribute to
this knowledge gap, a quantitative rehabilitation approach was applied for
characterizing upper extremity biomechanics of manual wheelchair mobility in
children and adolescents during propulsion, starting, and stopping tasks. A Vicon
motion analysis system captured movement, while a SmartWheel simultaneously
collected three-dimensional forces and moments occurring at the handrim. A custom
pediatric inverse dynamics model was used to evaluate three-dimensional upper
extremity joint motions, forces, and moments of 14 children with spinal cord
injury (SCI) during the functional tasks. Additionally, pain and health-related
quality of life outcomes were assessed. This research found that joint demands
are significantly different amongst functional tasks, with greatest demands
placed on the shoulder during the starting task. Propulsion was significantly
different from starting and stopping at all joints. We identified multiple stroke
patterns used by the children, some of which are not standard in adults. One
subject reported average daily pain, which was minimal. Lower than normal
physical health and higher than normal mental health was found in this
population. It can be concluded that functional tasks should be considered in
addition to propulsion for rehabilitation and SCI treatment planning. This
research provides wheelchair users and clinicians with a comprehensive,
biomechanical, mobility assessment approach for wheelchair prescription,
training, and long-term care of children with SCI.
PMID- 26442252
TI - Correcting Inconsistencies and Errors in Bacterial Genome Metadata Using an
Automated Curation Tool in Excel (AutoCurE).
AB - Whole-genome data are invaluable for large-scale comparative genomic studies.
Current sequencing technologies have made it feasible to sequence entire
bacterial genomes with relative ease and time with a substantially reduced cost
per nucleotide, hence cost per genome. More than 3,000 bacterial genomes have
been sequenced and are available at the finished status. Publically available
genomes can be readily downloaded; however, there are challenges to verify the
specific supporting data contained within the download and to identify errors and
inconsistencies that may be present within the organizational data content and
metadata. AutoCurE, an automated tool for bacterial genome database curation in
Excel, was developed to facilitate local database curation of supporting data
that accompany downloaded genomes from the National Center for Biotechnology
Information. AutoCurE provides an automated approach to curate local genomic
databases by flagging inconsistencies or errors by comparing the downloaded
supporting data to the genome reports to verify genome name, RefSeq accession
numbers, the presence of archaea, BioProject/UIDs, and sequence file
descriptions. Flags are generated for nine metadata fields if there are
inconsistencies between the downloaded genomes and genomes reports and if
erroneous or missing data are evident. AutoCurE is an easy-to-use tool for local
database curation for large-scale genome data prior to downstream analyses.
PMID- 26442253
TI - Car Transfer and Wheelchair Loading Techniques in Independent Drivers with
Paraplegia.
AB - Car transfers and wheelchair (WC) loading are crucial for independent community
participation in persons with complete paraplegia from spinal cord injury, but
are complex, physically demanding, and known to provoke shoulder pain. This study
aimed to describe techniques and factors influencing car transfer and WC loading
for individuals with paraplegia driving their own vehicles and using their
personal WCs. Sedans were the most common vehicle driven (59%). Just over half
(52%) of drivers place their right leg only into the vehicle prior to transfer.
Overall, the leading hand was most frequently placed on the driver's seat (66%)
prior to transfer and the trailing hand was most often place on the WC seat
(48%). Vehicle height influenced leading hand placement but not leg placement
such that drivers of higher profile vehicles were more likely to place their hand
on the driver's seat than those who drove sedans. Body lift time was negatively
correlated with level of injury and age and positively correlated with vehicle
height and shoulder abduction strength. Drivers who transferred with their
leading hand on the steering wheel had significantly higher levels of shoulder
pain than those who placed their hand on the driver's seat or overhead. The
majority of participants used both hands (62%) to load their WC frame, and
overall, most loaded their frame into the back (62%) vs. the front seat. Sedan
drivers were more likely to load their frame into the front seat than drivers of
higher profile vehicles (53 vs. 17%). Average time to load the WC frame (10.7 s)
was 20% of the total WC loading time and was not related to shoulder strength,
frame weight, or demographic characteristics. Those who loaded their WC frame
into the back seat had significantly weaker right shoulder internal rotators.
Understanding car transfers and WC loading in independent drivers is crucial to
prevent shoulder pain and injury and preserve community participation.
PMID- 26442254
TI - A New MRI-Based Model of Heart Function with Coupled Hemodynamics and Application
to Normal and Diseased Canine Left Ventricles.
AB - A methodology for the simulation of heart function that combines an MRI-based
model of cardiac electromechanics (CE) with a Navier-Stokes-based hemodynamics
model is presented. The CE model consists of two coupled components that simulate
the electrical and the mechanical functions of the heart. Accurate
representations of ventricular geometry and fiber orientations are constructed
from the structural magnetic resonance and the diffusion tensor MR images,
respectively. The deformation of the ventricle obtained from the
electromechanical model serves as input to the hemodynamics model in this one-way
coupled approach via imposed kinematic wall velocity boundary conditions and at
the same time, governs the blood flow into and out of the ventricular volume. The
time-dependent endocardial surfaces are registered using a diffeomorphic mapping
algorithm, while the intraventricular blood flow patterns are simulated using a
sharp-interface immersed boundary method-based flow solver. The utility of the
combined heart-function model is demonstrated by comparing the hemodynamic
characteristics of a normal canine heart beating in sinus rhythm against that of
the dyssynchronously beating failing heart. We also discuss the potential of
coupled CE and hemodynamics models for various clinical applications.
PMID- 26442255
TI - Fragmentation and Coverage Variation in Viral Metagenome Assemblies, and Their
Effect in Diversity Calculations.
AB - Metagenomic libraries consist of DNA fragments from diverse species, with varying
genome size and abundance. High-throughput sequencing platforms produce large
volumes of reads from these libraries, which may be assembled into contigs,
ideally resembling the original larger genomic sequences. The uneven species
distribution, along with the stochasticity in sample processing and sequencing
bias, impacts the success of accurate sequence assembly. Several assemblers
enable the processing of viral metagenomic data de novo, generally using overlap
layout consensus or de Bruijn graph approaches for contig assembly. The success
of viral genomic reconstruction in these datasets is limited by the degree of
fragmentation of each genome in the sample, which is dependent on the sequencing
effort and the genome length. Depending on ecological, biological, or procedural
biases, some fragments have a higher prevalence, or coverage, in the assembly.
However, assemblers must face challenges, such as the formation of chimerical
structures and intra-species variability. Diversity calculation relies on the
classification of the sequences that comprise a metagenomic dataset. Whenever the
corresponding genomic and taxonomic information is available, contigs matching
the same species can be classified accordingly and the coverage of its genome can
be calculated for that species. This may be used to compare populations by
estimating abundance and assessing species distribution from this data.
Nevertheless, the coverage does not take into account the degree of
fragmentation, or else genome completeness, and is not necessarily representative
of actual species distribution in the samples. Furthermore, undetermined
sequences are abundant in viral metagenomic datasets, resulting in several
independent contigs that cannot be assigned by homology or genomic information.
These may only be classified as different operational taxonomic units (OTUs),
sometimes remaining inadvisably unrelated. Thus, calculations using contigs as
different OTUs ultimately overestimate diversity when compared to diversity
calculated from species coverage. In order to compare the effect of coverage and
fragmentation, we generated three sets of simulated Illumina paired-end reads
with different sequencing depths. We compared different assemblies performed with
RayMeta, CLC Assembly Cell, MEGAHIT, SPAdes, Meta-IDBA, SOAPdenovo, Velvet,
Metavelvet, and MIRA with the best attainable assemblies for each dataset (formed
by arranging data using known genome coordinates) by calculating different
assembly statistics. A new fragmentation score was included to estimate the
degree of genome fragmentation of each taxon and adjust the coverage accordingly.
The abundance in the metagenome was compared by bootstrapping the assembly data
and hierarchically clustering them with the best possible assembly. Additionally,
richness and diversity indexes were calculated for all the resulting assemblies
and were assessed under two distributions: contigs as independent OTUs and
sequences classified by species. Finally, we search for the strongest
correlations between the diversity indexes and the different assembly statistics.
Although fragmentation was dependent of genome coverage, it was not as heavily
influenced by the assembler. The sequencing depth was the predominant attractor
that influenced the success of the assemblies. The coverage increased notoriously
in larger datasets, whereas fragmentation values remained lower and unsaturated.
While still far from obtaining the ideal assemblies, the RayMeta, SPAdes, and the
CLC assemblers managed to build the most accurate contigs with larger datasets
while Meta-IDBA showed a good performance with the medium-sized dataset, even
after the adjusted coverage was calculated. Their resulting assemblies showed the
highest coverage scores and the lowest fragmentation values. Alpha diversity
calculated from contigs as OTUs resulted in significantly higher values for all
assemblies when compared with actual species distribution, showing an
overestimation due to the increased predicted abundance. Conversely, using PHACCS
resulted in lower values for all assemblers. Different association methods
(random-forest, generalized linear models, and the Spearman correlation index)
support the number of contigs, the coverage, and fragmentation as the assembly
parameters that most affect the estimation of the alpha diversity. Coverage
calculations may provide an insight into relative completeness of a genome but
they overlook missing fragments or overly separated sequences in a genome. The
assembly of a highly fragmented genomes with high coverage may still lead to the
clustering of different OTUs that are actually different fragments of a genome.
Thus, it proves useful to penalize coverage with a fragmentation score. Using
contigs for calculating alpha diversity result in overestimation but it is
usually the only approach available. Still, it is enough for sample comparison.
The best approach may be determined by choosing the assembler that better fits
the sequencing depth and adjusting the parameters for longer accurate contigs
whenever possible whereas diversity may be calculated considering taxonomical and
genomic information if available.
PMID- 26442256
TI - The Golden Age in Cancer Nanobiotechnology: Quo Vadis?
PMID- 26442258
TI - On Accounting for Sequence-Specific Bias in Genome-Wide Chromatin Accessibility
Experiments: Recent Advances and Contradictions.
PMID- 26442257
TI - Tandem Repeats in Proteins: Prediction Algorithms and Biological Role.
AB - Tandem repetitions in protein sequence and structure is a fascinating subject of
research which has been a focus of study since the late 1990s. In this survey, we
give an overview on the multi-faceted aspects of research on protein tandem
repeats (PTR for short), including prediction algorithms, databases, early
classification efforts, mechanisms of PTR formation and evolution, and synthetic
PTR design. We also touch on the rather open issue of the relationship between
PTR and flexibility (or disorder) in proteins. Detection of PTR either from
protein sequence or structure data is challenging due to inherent high
(biological) signal-to-noise ratio that is a key feature of this problem. As
early in silico analytic tools have been key enablers for starting this field of
study, we expect that current and future algorithmic and statistical
breakthroughs will have a high impact on the investigations of the biological
role of PTR.
PMID- 26442259
TI - Shikimic Acid Production in Escherichia coli: From Classical Metabolic
Engineering Strategies to Omics Applied to Improve Its Production.
AB - Shikimic acid (SA) is an intermediate of the SA pathway that is present in
bacteria and plants. SA has gained great interest because it is a precursor in
the synthesis of the drug oseltamivir phosphate (OSF), an efficient inhibitor of
the neuraminidase enzyme of diverse seasonal influenza viruses, the avian
influenza virus H5N1, and the human influenza virus H1N1. For the purposes of OSF
production, SA is extracted from the pods of Chinese star anise plants (Illicium
spp.), yielding up to 17% of SA (dry basis content). The high demand for OSF
necessary to manage a major influenza outbreak is not adequately met by
industrial production using SA from plants sources. As the SA pathway is present
in the model bacteria Escherichia coli, several "intuitive" metabolically
engineered strains have been applied for its successful overproduction by
biotechnological processes, resulting in strains producing up to 71 g/L of SA,
with high conversion yields of up to 0.42 (mol SA/mol Glc), in both batch and fed
batch cultures using complex fermentation broths, including glucose as a carbon
source and yeast extract. Global transcriptomic analyses have been performed in
SA-producing strains, resulting in the identification of possible key target
genes for the design of a rational strain improvement strategy. Because possible
target genes are involved in the transport, catabolism, and interconversion of
different carbon sources and metabolic intermediates outside the central carbon
metabolism and SA pathways, as genes involved in diverse cellular stress
responses, the development of rational cellular strain improvement strategies
based on omics data constitutes a challenging task to improve SA production in
currently overproducing engineered strains. In this review, we discuss the main
metabolic engineering strategies that have been applied for the development of
efficient SA-producing strains, as the perspective of omics analysis has focused
on further strain improvement for the production of this valuable aromatic
intermediate.
PMID- 26442260
TI - Optimization of Alkaline and Dilute Acid Pretreatment of Agave Bagasse by
Response Surface Methodology.
AB - Utilization of lignocellulosic materials for the production of value-added
chemicals or biofuels generally requires a pretreatment process to overcome the
recalcitrance of the plant biomass for further enzymatic hydrolysis and
fermentation stages. Two of the most employed pretreatment processes are the ones
that used dilute acid (DA) and alkaline (AL) catalyst providing specific effects
on the physicochemical structure of the biomass, such as high xylan and lignin
removal for DA and AL, respectively. Another important effect that need to be
studied is the use of a high solids pretreatment (>=15%) since offers many
advantaged over lower solids loadings, including increased sugar and ethanol
concentrations (in combination with a high solids saccharification), which will
be reflected in lower capital costs; however, this data is currently limited. In
this study, several variables, such as catalyst loading, retention time, and
solids loading, were studied using response surface methodology (RSM) based on a
factorial central composite design of DA and AL pretreatment on agave bagasse
using a range of solids from 3 to 30% (w/w) to obtain optimal process conditions
for each pretreatment. Subsequently enzymatic hydrolysis was performed using
Novozymes Cellic CTec2 and HTec2 presented as total reducing sugar (TRS) yield.
Pretreated biomass was characterized by wet-chemistry techniques and selected
samples were analyzed by calorimetric techniques, and scanning electron/confocal
fluorescent microscopy. RSM was also used to optimize the pretreatment conditions
for maximum TRS yield. The optimum conditions were determined for AL
pretreatment: 1.87% NaOH concentration, 50.3 min and 13.1% solids loading,
whereas DA pretreatment: 2.1% acid concentration, 33.8 min and 8.5% solids
loading.
PMID- 26442261
TI - Fluorescent Reporter Libraries as Useful Tools for Optimizing Microbial Cell
Factories: A Review of the Current Methods and Applications.
AB - The use of genetically encoded fluorescent reporters allows speeding up the
initial optimization steps of microbial bioprocesses. These reporters can be used
for determining the expression level of a particular promoter, not only the
synthesis of a specific protein but also the content of intracellular
metabolites. The level of protein/metabolite is thus proportional to a
fluorescence signal. By this way, mean expression profiles of protein/metabolites
can be determined non-invasively at a high-throughput rate, allowing the rapid
identification of the best producers. Actually, different kinds of reporter
systems are available, as well as specific cultivation devices allowing the on
line recording of the fluorescent signal. Cell-to-cell variability is another
important phenomenon that can be integrated into the screening procedures for the
selection of more efficient microbial cell factories.
PMID- 26442262
TI - Clueless with fewer cues from endothelin. Commentary: Venous endothelin guides
sympathetic innervation of the developing mouse heart.
PMID- 26442264
TI - Slow conduction in mixed cultured strands of primary ventricular cells and stem
cell-derived cardiomyocytes.
AB - Modern concepts for the treatment of myocardial diseases focus on novel cell
therapeutic strategies involving stem cell-derived cardiomyocytes (SCMs).
However, functional integration of SCMs requires similar electrophysiological
properties as primary cardiomyocytes (PCMs) and the ability to establish
intercellular connections with host myocytes in order to contribute to the
electrical and mechanical activity of the heart. The aim of this project was to
investigate the properties of cardiac conduction in a co-culture approach using
SCMs and PCMs in cultured cell strands. Murine embryonic SCMs were pooled with
fetal ventricular cells and seeded in predefined proportions on microelectrode
arrays to form patterned strands of mixed cells. Conduction velocity (CV) was
measured during steady state pacing. SCM excitability was estimated from action
potentials measured in single cells using the patch clamp technique. Experiments
were complemented with computer simulations of conduction using a detailed model
of cellular architecture in mixed cell strands. CV was significantly lower in
strands composed purely of SCMs (5.5 +/- 1.5 cm/s, n = 11) as compared to PCMs
(34.9 +/- 2.9 cm/s, n = 21) at similar refractoriness (100% SCMs: 122 +/- 25 ms,
n = 9; 100% PCMs: 139 +/- 67 ms, n = 14). In mixed strands combining both cell
types, CV was higher than in pure SCMs strands, but always lower than in 100% PCM
strands. Computer simulations demonstrated that both intercellular coupling and
electrical excitability limit CV. These data provide evidence that in cultures of
murine ventricular cardiomyocytes, SCMs cannot restore CV to control levels
resulting in slow conduction, which may lead to reentry circuits and arrhythmias.
PMID- 26442265
TI - Viscoelastic Methods of Blood Clotting Assessment - A Multidisciplinary Review.
AB - Viscoelastic methods (VEM) made available the bedside assessment of blood
clotting. Unlike standard laboratory tests, the results are based on the whole
blood coagulation and are available in real time at a much faster turnaround
time. In combination with our new knowledge about pathophysiology of the trauma
induced coagulopathy, the goal-oriented treatment protocols have been recently
proposed for the initial management of bleeding in trauma victims. Additionally,
the utility of viscoelastic monitoring devices has been proved even outside this
setting in cardiosurgical patients or those undergoing liver transplantation.
Many other situations were described in literature showing the potential use of
bedside analysis of coagulation for the management of bleeding or critically ill
patients. In the near future, we may expect further improvement in current
bedside diagnostic tools enabling not only the assessment of secondary hemostasis
but also the platelet aggregation. More sensitive assays for new anticoagulants
are underway. Aim of this review is to offer the reader a multidisciplinary
overview of VEM and their potential use in anesthesiology and critical care.
PMID- 26442266
TI - Insights into Regulation of the miR-17-92 Cluster of miRNAs in Cancer.
AB - Overexpression of the miR-17-92 cluster is a key oncogenic event in various
cancer types. The oncogenic effect of the miR-17-92 cluster is enhanced by
cooperation between its members in targeting tumor-suppressive proteins and
pathways such as PTEN and TGFbeta signaling. However, in the case of miR-19a and
miR-19b, these have been shown to have a preponderant role in the cluster's
oncogenicity. Important studies have revealed the influence of the Myc proto
oncogene family in the transcriptional regulation of miR-17-92. Recent findings
show that other oncogenic signaling pathways, such as those of Notch and Sonic
Hedgehog, activate miR-17-92 in cancer. Notwithstanding, another layer of
complexity has been added by the influence of the relevant primary miR-17-92
tertiary structure during processing to mature miRNA. In this review, we attempt
to integrate current transcriptional and post-transcriptional knowledge to
enhance our global understanding of the coordinated up-regulation of miR-17-92 in
cancer.
PMID- 26442263
TI - The different facets of organelle interplay-an overview of organelle
interactions.
AB - Membrane-bound organelles such as mitochondria, peroxisomes, or the endoplasmic
reticulum (ER) create distinct environments to promote specific cellular tasks
such as ATP production, lipid breakdown, or protein export. During recent years,
it has become evident that organelles are integrated into cellular networks
regulating metabolism, intracellular signaling, cellular maintenance, cell fate
decision, and pathogen defence. In order to facilitate such signaling events,
specialized membrane regions between apposing organelles bear distinct sets of
proteins to enable tethering and exchange of metabolites and signaling molecules.
Such membrane associations between the mitochondria and a specialized site of the
ER, the mitochondria associated-membrane (MAM), as well as between the ER and the
plasma membrane (PAM) have been partially characterized at the molecular level.
However, historical and recent observations imply that other organelles like
peroxisomes, lysosomes, and lipid droplets might also be involved in the
formation of such apposing membrane contact sites. Alternatively, reports on so
called mitochondria derived-vesicles (MDV) suggest alternative mechanisms of
organelle interaction. Moreover, maintenance of cellular homeostasis requires the
precise removal of aged organelles by autophagy-a process which involves the
detection of ubiquitinated organelle proteins by the autophagosome membrane,
representing another site of membrane associated-signaling. This review will
summarize the available data on the existence and composition of organelle
contact sites and the molecular specializations each site uses in order to
provide a timely overview on the potential functions of organelle interaction.
PMID- 26442267
TI - Story of Rubidium-82 and Advantages for Myocardial Perfusion PET Imaging.
AB - Rubidium-82 has a long story, starting in 1954. After preclinical studies in dogs
showing that myocardial uptake of this radionuclide was directly proportional to
myocardial blood flow (MBF), clinical studies were performed in the 80s leading
to an approval in the USA in 1989. From that time, thousands of patients have
been tested and their results have been reported in three meta-analyses. Pooled
patient-based sensitivity and specificity were, respectively, 0.91 and 0.90. By
comparison with (99m)Tc-SPECT, (82)Rb PET had a much better diagnostic accuracy,
especially in obese patients with body mass index >=30 kg/m(2) (85 versus 67%
with SPECT) and in women with large breasts. A great advantage of (82)Rb PET is
its capacity to accurately quantify MBF. Quite importantly, it has been recently
shown that coronary flow reserve is associated with adverse cardiovascular events
independently of luminal angiographic severity. Moreover, coronary flow reserve
is a functional parameter particularly useful in the estimate of microvascular
dysfunction, such as in diabetes mellitus. Due to the very short half-life of
rubidium-82, the effective dose calculated for a rest/stress test is roughly
equivalent to the annual natural exposure and even less when stress-only is
performed with a low activity compatible with a good image quality with the last
generation 3D PET scanners. There is still some debate on the relative advantages
of (82)Rb PET with regard to (99m)Tc-SPECT. For the last 10 years, great
technological advances substantially improved performances of SPECT with its
accuracy getting closer to this of (82)Rb/PET. Currently, the main advantages of
PET are its capacity to accurately quantify MBF and to deliver a low radiation
exposure.
PMID- 26442268
TI - Corrigendum: Escherichia coli Isolated from Urinary Tract Infections of Lebanese
Patients between 2005 and 2012: Epidemiology and Profiles of Resistance.
AB - [This corrects the article on p. 26 in vol. 2, PMID: 4415468.].
PMID- 26442269
TI - Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with
(18)F-Choline PET/CT in Prostate Cancer.
AB - INTRODUCTION: Dynamic image acquisition with (18)F-Choline [fluorocholine (FCH)]
PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which
could obstruct the loco-regional analysis. The aim of our study was to analyze
early dynamic FCH acquisitions to define pelvic lymph node or prostate
pathological status. MATERIAL AND METHODS: Retrospective analysis was performed
on 39 patients for initial staging (n = 18), or after initial treatment (n = 21).
Patients underwent 10-min dynamic acquisitions centered on the pelvis, after
injection of 3-4 MBq/kg of FCH. Whole-body images were acquired about 1 h after
injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT).
Maximum and mean SUV according to time were measured on nodal and prostatic
lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable
recovery coefficients. The status of each lesion was based on histological
results or patient follow-up (>6 months). A Mann-Whitney test and ANOVA were used
to compare mean and receiver operating characteristic (ROC) curve analysis.
RESULTS: The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4.
Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed,
including 63 malignant lesions. In early dynamic acquisitions, the maximum and
mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant
versus benign lesions (p < 0.001, p < 0.001). Mean SUV without PVEC, allowed
better discrimination of benign from malignant lesions, in comparison with
maximum and mean SUV (with PVEC), for both early and late acquisitions. For
patients acquired on mCT, area under the ROC curve showed a trend to better
sensitivity and specificity for early acquisitions, compared with late
acquisitions (SUVmax AUC 0.92 versus 0.85, respectively). CONCLUSION: Assessment
of lymph nodes and prostate pathological status with early dynamic imaging using
PET/CT FCH allowed prostate cancer detection in situations where proof of
malignancy is difficult to obtain.
PMID- 26442270
TI - Pseudogenes in Human Cancer.
AB - Recent advances in the analysis of RNA sequencing data have shown that
pseudogenes are highly specific markers of cell identity and can be used as
diagnostic and prognostic markers. Furthermore, genetically engineered mouse
models have recently provided compelling support for a causal link between
altered pseudogene expression and cancer. In this review, we discuss the most
recent milestones reached in the pseudogene field and the use of pseudogenes as
cancer classifiers.
PMID- 26442271
TI - Interleukin(IL)-36alpha and IL-36gamma Induce Proinflammatory Mediators from
Human Colonic Subepithelial Myofibroblasts.
AB - BACKGROUND: Interleukin (IL)-36 cytokines are recently reported member of the IL
1 cytokine family. However, there is little information regarding the association
between IL-36 cytokines and gut inflammation. In the present study, we
investigated the biological activity of IL-36alpha and IL-36gamma using human
colonic subepithelial myofibroblasts (SEMFs). METHODS: The mRNA expression and
the protein expression of target molecules in SEMFs were evaluated using real
time polymerase chain reaction and enzyme-linked immunosorbent assay,
respectively. The intracellular signaling of IL-36 cytokines was analyzed using
Western blot analysis and small interfering RNAs (siRNAs) specific for MyD88
adaptor proteins (MyD88 and IRAK1) and NF-kappaB p65. RESULTS: IL-36alpha and IL
36gamma significantly enhanced the secretion of IL-6 and CXC chemokines (CXCL1,
CXCL2, and CXCL8) by SEMFs. The combination of IL-36alpha/gamma and IL-17A or of
IL-36alpha/gamma and tumor necrosis factor-alpha showed a synergistic effect on
the induction of IL-6 and CXC chemokines. The mRNA expression of proinflammatory
mediators induced by IL-36alpha and/or IL-36gamma was significantly suppressed by
transfection of siRNA for MyD88 or IRAK1. Both inhibitors of mitogen activated
protein kinases and siRNAs specific for NF-kappaBp65 significantly reduced the
expression of IL-6 and CXC chemokines induced by IL-36alpha and/or IL-36gamma.
CONCLUSION: These results suggest that IL-36alpha and IL-36gamma contribute to
gut inflammation through the induction of proinflammatory mediators.
PMID- 26442273
TI - Post-Exercise Skeletal Muscle Glycogen Related to Plasma Cytokines and Muscle IL
6 Protein Content, but not Muscle Cytokine mRNA Expression.
AB - OBJECTIVES: The purpose of this study was to correlate post-exercise muscle
glycogen levels with changes in plasma cytokine, and muscle mRNA cytokine
expression and protein content. METHODS: Twenty-four male runners (age 36.5 +/-
1.8 years, VO2max 60.0 +/- 1.5 mL?kg(-1) ? min(-1)) ran twice (separated by 4
weeks) on treadmills to exhaustion at 70% VO2max (average time and distance of
2.24 +/- 0.09 h and 24.9 +/- 1.1 km). Muscle biopsies from the vastus lateralis
and blood samples were collected before and after each run, with IL-6, IL-8, and
MCP-1 measured in muscle (mRNA and protein) and plasma. Data from the two runs
were averaged. RESULTS: Participants experienced a 35.3 +/- 4.2% decrease (P <
0.001) in skeletal muscle glycogen content (67.5 +/- 2.8 to 44.3 +/- 3.7 mmol?kg(
1) wet weight). Muscle mRNA expression for IL-6, IL-8, and MCP-1 increased 7.34
+/- 0.90-, 13.9 +/- 2.3-, and 4.10 +/- 0.60-fold, respectively (all, P < 0.001).
Skeletal muscle IL-6, IL-8, and MCP-1 protein content increased 35.8 +/- 10.6,
80.6 +/- 12.1, and 105 +/- 17.9%, respectively (all, P <= 0.005). Plasma IL-6, IL
8, and MCP-1 increased 47.1 +/- 10.0-, 2.6 +/- 0.3-, and 1.6 +/- 0.1-fold,
respectively (all, P < 0.001). Post-exercise muscle glycogen concentrations were
negatively correlated with run time to exhaustion (r = -0.70, P < 0.001), and
changes in muscle IL-6 protein content (r = -0.44, P = 0.049), plasma IL-6 (r =
0.72, P < 0.001), IL-8 (r = -0.60, P = 0.002), and MCP-1 (r = -0.589, P = 0.002),
but not with changes in muscle IL-8 and MCP-1 protein content, or muscle mRNA
expression for IL-6, IL-8, and MCP-1. CONCLUSION: Prolonged and intensive running
increased muscle mRNA expression, muscle protein content, and plasma levels for
IL-6, IL-8, and MCP-1, and post-run muscle glycogen levels were most strongly
related to plasma cytokine levels.
PMID- 26442272
TI - Goals in Nutrition Science 2015-2020.
PMID- 26442275
TI - Integrating Environmental Sustainability Considerations into Food and Nutrition
Policies: Insights from Australia's National Food Plan.
AB - The environmental sustainability (ES) of food systems is a critical challenge for
policy makers. This is a highly contested policy area with differing views among
stakeholders. The aim of the study was to develop a better understanding of how
ES considerations are addressed in Australian food and nutrition policies and the
way that consultation processes affect final policy outcomes. A mixed-methods
study design combined a detailed chronology of key policy developments (2009
2015), a content analysis of written submissions obtained during the NFP's
consultation period (2011-2013) and a frame analysis of the sustainability
perspectives - efficiency, demand restraint, and system transformation - in the
NFP's Issues, Green, and White Papers. There were 555 written submissions
responding to two consultation papers. Stakeholders represented all sectors of
Australia's food system including government, non-government organizations, the
food supply chain, research and academic institutions, and members of the general
public. Around 74% of submissions referred to ES considerations and ~65%
supported their inclusion into the final policy. Efficiency frames were most
dominant; emphasizing a production-oriented approach that regards the environment
as a natural resource base for food production but overlooks consumption and
equity concerns. Despite strong support for the inclusion of ES considerations in
the NFP, the influence of Australia's socio-political context, powerful, industry
dominated stakeholders, and a reliance on traditional production-oriented
perspectives delivered a business-as-usual approach to food policy making. It has
since been replaced by an agricultural strategy that provides only cursory
attention to ES. Our findings indicate that Australia's political environment is
not sufficiently mature for ES considerations to be integrated into food and
nutrition policies. We propose reforms to the current consultation process in
Australia to better support this integration by promoting greater transparency
and participation in the development of food and nutrition policy making.
PMID- 26442274
TI - Biogas Cook Stoves for Healthy and Sustainable Diets? A Case Study in Southern
India.
AB - Alternative cook stoves that replace solid fuels with cleaner energy sources,
such as biogas, are gaining popularity in low-income settings across Asia,
Africa, and South America. Published research on these technologies focuses on
their potential to reduce indoor air pollution and improve respiratory health.
Effects on other cooking-related aspects, such as diets and women's time
management, are less understood. In this study, in southern India, we investigate
if using biogas cook stoves alters household diets and women's time management.
We compare treatment households who are supplied with a biogas cook stove with
comparison households who do not have access to these stoves, while controlling
for several socio-economic factors. We find that diets of treatment households
are more diverse than diets of comparison households. In addition, women from
treatment households spend on average 40 min less cooking and 70 min less
collecting firewood per day than women in comparison households. This study
illustrates that alongside known benefits for respiratory health, using
alternative cook stoves may benefit household diets and free up women's time. To
inform development investments and ensure these co-benefits, we argue that
multiple dimensions of sustainability should be considered in evaluating the
impact of alternative cook stoves.
PMID- 26442276
TI - Can the Hydroxyapatite-Coated Skin-Penetrating Abutment for Bone Conduction
Hearing Implants Integrate with the Surrounding Skin?
AB - INTRODUCTION: Percutaneous implants, such as bone conduction hearing implants,
suffer from complications that include inflammation of the surrounding skin. A
sealed skin-abutment interface can prevent the ingress of bacteria, which should
reduce the occurrence of peri-abutment dermatitis. It was hypothesized that a
hydroxyapatite (HA)-coated abutment in conjunction with soft tissue preservation
surgery should enable integration with the adjacent skin. Previous research has
confirmed that integration is never achieved with as-machined titanium abutments.
Here, we investigate, in vivo, if skin integration is achievable in patients
using a HA-coated abutment. MATERIALS AND METHODS: One titanium abutment
(control) and one HA-coated abutment (case) together with the surrounding skin
were surgically retrieved from two patients who had a medical indication for this
procedure. Histological sections of the skin were investigated using light
microscopy. The abutment was qualitatively analyzed using scanning electron
microscopy. RESULTS: The titanium abutment only had a partial and thin layer of
attached amorphous biological material. The HA-coated abutment was almost fully
covered by a pronounced thick layer of organized skin, composed of different
interconnected structural layers. CONCLUSION: Proof-of-principle evidence that
the HA-coated abutment can achieve integration with the surrounding skin was
presented for the first time.
PMID- 26442277
TI - Hearts Not Dead after Circulatory Death.
PMID- 26442278
TI - Rigid Posterior Lumbopelvic Fixation without Formal Debridement for Pyogenic
Vertebral Diskitis and Osteomyelitis Involving the Lumbosacral Junction:
Technical Report.
AB - BACKGROUND: Pelvic fixation with S2-alar-iliac (S2AI) screws can increase the
rigidity of a lumbosacral construct, which may promote bone healing, improve
antibiotic delivery to infected tissues, and avoid L5-S1 pseudarthrosis. PURPOSE:
To describe the use of single-stage posterior fixation without debridement for
the treatment of pyogenic vertebral diskitis and osteomyelitis (PVDO) at the
lumbosacral junction. STUDY DESIGN: Technical report. METHODS: We describe the
management of PVDO at the lumbosacral junction in which the infection invaded the
endplates, disk space, vertebrae, prevertebral soft tissues, and epidural space.
Pedicle involvement precluded screw fixation at L5. Surgical management consisted
of a single-stage posterior operation with rigid lumbopelvic fixation augmented
with S2-alar-iliac screws and without formal debridement of the infected area,
followed by long-term antibiotic treatment. RESULTS: At 2-year follow-up,
successful fusion and eradication of the infection were achieved. CONCLUSION:
PVDO at the lumbosacral junction may be treated successfully using rigid
posterior-only fixation without formal debridement combined with antibiotic
therapy.
PMID- 26442279
TI - Biological Meshes for Inguinal Hernia Repair - Review of the Literature.
AB - INTRODUCTION: Biological meshes are a potential alternative to the synthetic
meshes to avoid complications and are used in a contaminated field for
incarcerated inguinal hernias. The clinical experiences gained with biological
meshes for repair of inguinal hernias are presented in this review. MATERIALS AND
METHODS: In a literature search of the Medline database using the key word
"Biological mesh," 2,277 citations were found. There remained 14 studies in which
biological meshes had been used to repair inguinal hernias. RESULTS: In
prospective randomized trials, the use of polypropylene vs. biological meshes was
compared in open inguinal hernia repair. There was no difference in the
recurrence rate, but differences were observed in the postsurgical pain incidence
in favor of the biological mesh. In the remaining retrospective studies, the
recurrence rates were also acceptable. The biological mesh was used successfully
in a potentially contaminated setting. CONCLUSION: Inguinal hernias can be
repaired with biological meshes with reasonable recurrence rate, also as an
alternative in a potentially contaminated field.
PMID- 26442280
TI - Commentary: How Long Do We Need to Follow-Up Our Hernia Patients to Find the Real
Recurrence Rate?
PMID- 26442281
TI - Physicochemical characteristics of structurally determined metabolite-protein and
drug-protein binding events with respect to binding specificity.
AB - To better understand and ultimately predict both the metabolic activities as well
as the signaling functions of metabolites, a detailed understanding of the
physical interactions of metabolites with proteins is highly desirable. Focusing
in particular on protein binding specificity vs. promiscuity, we performed a
comprehensive analysis of the physicochemical properties of compound-protein
binding events as reported in the Protein Data Bank (PDB). We compared the
molecular and structural characteristics obtained for metabolites to those of the
well-studied interactions of drug compounds with proteins. Promiscuously binding
metabolites and drugs are characterized by low molecular weight and high
structural flexibility. Unlike reported for drug compounds, low rather than high
hydrophobicity appears associated, albeit weakly, with promiscuous binding for
the metabolite set investigated in this study. Across several physicochemical
properties, drug compounds exhibit characteristic binding propensities that are
distinguishable from those associated with metabolites. Prediction of target
diversity and compound promiscuity using physicochemical properties was possible
at modest accuracy levels only, but was consistently better for drugs than for
metabolites. Compound properties capturing structural flexibility and hydrogen
bond formation descriptors proved most informative in PLS-based prediction
models. With regard to diversity of enzymatic activities of the respective
metabolite target enzymes, the metabolites benzylsuccinate, hypoxanthine,
trimethylamine N-oxide, oleoylglycerol, and resorcinol showed very narrow process
involvement, while glycine, imidazole, tryptophan, succinate, and glutathione
were identified to possess broad enzymatic reaction scopes. Promiscuous
metabolites were found to mainly serve as general energy currency compounds, but
were identified to also be involved in signaling processes and to appear in
diverse organismal systems (digestive and nervous system) suggesting specific
molecular and physiological roles of promiscuous metabolites.
PMID- 26442282
TI - Ion-pumping microbial rhodopsins.
AB - Rhodopsins are light-sensing proteins used in optogenetics. The word "rhodopsin"
originates from the Greek words "rhodo" and "opsis," indicating rose and sight,
respectively. Although the classical meaning of rhodopsin is the red-colored
pigment in our eyes, the modern meaning of rhodopsin encompasses photoactive
proteins containing a retinal chromophore in animals and microbes. Animal and
microbial rhodopsins possess 11-cis and all-trans retinal, respectively, to
capture light in seven transmembrane alpha-helices, and photoisomerizations into
all-trans and 13-cis forms, respectively, initiate each function. Ion
transporting proteins can be found in microbial rhodopsins, such as light-gated
channels and light-driven pumps, which are the main tools in optogenetics. Light
driven pumps, such as archaeal H(+) pump bacteriorhodopsin (BR) and Cl(-) pump
halorhodopsin (HR), were discovered in the 1970s, and their mechanism has been
extensively studied. On the other hand, different kinds of H(+) and Cl(-) pumps
have been found in marine bacteria, such as proteorhodopsin (PR) and Fulvimarina
pelagi rhodopsin (FR), respectively. In addition, a light-driven Na(+) pump was
found, Krokinobacter eikastus rhodopsin 2 (KR2). These light-driven ion-pumping
microbial rhodopsins are classified as DTD, TSA, DTE, NTQ, and NDQ rhodopsins for
BR, HR, PR, FR, and KR2, respectively. Recent understanding of ion-pumping
microbial rhodopsins is reviewed in this paper.
PMID- 26442283
TI - Molecular diagnostics of neurodegenerative disorders.
AB - Molecular diagnostics provide a powerful method to detect and diagnose various
neurological diseases such as Alzheimer's and Parkinson's disease. The
confirmation of such diagnosis allows early detection and subsequent medical
counseling that help specific patients to undergo clinically important drug
trials. This provides a medical pathway to have better insight of neurogenesis
and eventual cure of the neurodegenerative diseases. In this short review, we
present recent advances in molecular diagnostics especially biomarkers and
imaging spectroscopy for neurological diseases. We describe advances made in
Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis
(ALS) and Huntington's disease (HD), and finally present a perspective on the
future directions to provide a framework for further developments and refinements
of molecular diagnostics to combat neurodegenerative disorders.
PMID- 26442285
TI - Data in support of genome-wide identification of lineage-specific genes within
Caenorhabditis elegans.
AB - Two sets of LSGs were identified using BLAST: Caenorhabditis elegans species
specific genes (SSGs, 1423), and Caenorhabditis genus-specific genes (GSGs,
4539). The data contained in this article show SSGs and GSGs have significant
differences in evolution and that most of them were formed by gene duplication
and integration of transposable elements (TEs). Subsequent observation of
temporal expression and protein function presents that many SSGs and GSGs are
expressed and that genes involved with sex determination, specific stress, immune
response, and morphogenesis are most represented. The data are related to
research article "Genome-wide identification of lineage-specific genes within
Caenorhabditis elegans" in Journal of Genomics [1].
PMID- 26442284
TI - Diabetic Nephropathy Induced by Increased Ace Gene Dosage Is Associated with High
Renal Levels of Angiotensin (1-7) and Bradykinin.
AB - Population studies have shown an association between diabetic nephropathy (DN)
and insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme
(ACE) gene (ACE in humans, Ace in mice). The aim was to evaluate the modulation
of Ace copies number and diabetes mellitus (DM) on renal RAS and correlate it
with indicators of kidney function. Increased number of copies of the Ace gene,
associated with DM, induces renal dysfunction. The susceptibility to the
development of DN in 3 copies of animals is associated with an imbalance in
activity of RAS enzymes leading to increased synthesis of Ang II and Ang-(1-7).
Increased concentration of renal Ang-(1-7) appears to potentiate the deleterious
effects triggered by Ang II on kidney structure and function. Results also show
increased bradykinin concentration in 3 copies diabetic group. Taken together,
results indicate that the deleterious effects described in 3 copies diabetic
group are, at least in part, due to a combination of factors not usually
described in the literature. Thus, the data presented here show up innovative and
contribute to understanding the complex mechanisms involved in the development of
DN, in order to optimize the treatment of patients with this complication.
PMID- 26442286
TI - Data on pigments and long-chain fatty compounds identified in Dietzia sp. A14101
grown on simple and complex hydrocarbons.
AB - This data article provides: 1.An overview of tentatively identified long chain
compounds in Dietzia sp. A14101 grown on simple and complex
hydrocarbons;2.Preliminary Identification of pigments in bacterial material
obtained from incubation with a hydrocarbon (dodecane, n-C12) as the only carbon
and energy source;3.Some pictures to illustrate the cell surface charge test.
PMID- 26442287
TI - An enzyme-free colorimetric assay using hybridization chain reaction
amplification and split aptamers.
AB - A novel unmodified gold nanoparticle (AuNP)-based colorimetric assay was
demonstrated using split aptamers and the hybridization chain reaction (HCR)
amplification strategy. Here, the aptamer was divided into a structure-switching
hairpin probe (DNA probe H1 (or H1')) and a single-stranded probe (DNA probe H2
(or H2')). In the presence of the target, DNA probe H1 (or H1') could
specifically capture the target with the assistance of DNA probe H2 (or H2') to
form a stable complex. Subsequently, the hairpin structure of DNA probe H1 (or
H1') was changed, and then a chain reaction of hybridization events between two
other hairpin probes (H3 and H4) propagated, resulting in the formation of nicked
double-helices. Since it was difficult for such nicked double-helices to inhibit
salt-induced AuNP aggregation, a red-to-blue color change was observed. With the
elegant amplification effect of HCR, this assay showed a low detection limit (15
nM for Hg(2+) and 1 MUM for adenosine), which was lower than or at least
comparable to previous AuNP-based methods. The novel strategy not only eliminated
the requirements of enzymatic reactions, separation processes, chemical
modifications, and sophisticated instruments, but also could be used for other
targets only by simply changing the DNA probe sequences.
PMID- 26442288
TI - Response to Dr. Carbone's Letter to the Editor.
PMID- 26442289
TI - Surgical Correction of Rectal Prolapse in Laboratory Mice (Mus musculus).
AB - Rectal prolapse is a common clinical problem in laboratory mice. This condition
may occur spontaneously, develop after genetic manipulations, result from
infections with pathogens such as Citrobacter species, or arise secondary to
experimental design such as colitis models. The current standard of care at our
institution is limited to monitoring mice until tissue becomes ulcerated or
necrotic; this strategy often leads to premature euthanasia of valuable animals
prior to the study endpoint. Surgical correction of rectal prolapse is performed
routinely and with minimal complications in larger species by using manual
reduction with placement of a pursestring suture. In this report, we investigated
whether the use of a pursestring suture was an effective treatment for mice with
rectal prolapse. The procedure includes anesthetizing mice with isoflurane,
manually reducing prolapsed tissue, and placing a pursestring suture of 4-0
polydioxanone. We have performed this procedure successfully in 12 mice.
Complications included self-trauma, fecal impaction due to lack of defecation,
and mutilation of the surgical site by cage mates. Singly housing mice for 7 d
postoperatively, applying multimodal analgesia, and releasing the pursestring
when indicated eliminated these complications. The surgical repair of rectal
prolapses in mice is a minimally invasive procedure that resolves the clinical
symptoms of affected animals and reduces the number of mice that are euthanized
prematurely prior to the study endpoint.
PMID- 26442290
TI - DIESEL AND GASOLINE ENGINE EXHAUSTS AND SOME NITROARENES. IARC MONOGRAPHS ON THE
EVALUATION OF CARCINOGENIC RISKS TO HUMANS.
PMID- 26442291
TI - [Related factors of sperm DNA damage: Advances in studies].
AB - The detection of sperm DNA damage, as an important supplement to semen routine
examination strategies, has been applied in some clinical andrology laboratories.
What factors may lead to sperm DNA damage remains one of the concerns among many
andrologists. Present studies show a variety of factors of sperm DNA damage,
including age, environmental pollutants such as organophosphorus and
organochloride pesticides, plasticizer, heavy metals such as lead, carcinogens
such as polycyclic aromatic hydrocarbons (c-PAHs) and zearalenone (ZEA), male
reproductive system diseases or systemic diseases such as varicocele, infection,
tumor, spermatogenesis and maturation dysfunction, spinal cord injury and
endocrine disorders, seasons and temperature, lifestyle, abstinence time, semen
refrigeration, semen handling in vitro, and certain medications. Among them,
spermatogenesis and sperm maturation dysfunction may be the most secretive
factors, which are involved in the molecular mechanisms of sperm chromatin
packaging and restructuring, such as the transformation of histone to protamine,
single nucleotide polymorphism of genes, and the role of telomere, which may be
one of the hotspots in the future studies of sperm DNA damage. Relevant
researches in the future are expected to focus on the prevention of sperm DNA
damage and clarification of its specific pathogenic mechanisms so as to provide
some evidence for its treatment.
PMID- 26442292
TI - [Prostatic inflammation-induced chronic pelvic pain: Roles of substance P and c
fos in the spinal cord].
AB - OBJECTIVE: To explore the possible pain mechanism of chronic prostatitis/chronic
pelvic pain syndrome (CP/CPPS). METHODS: The models of CP/CPPS were established
in male Wistar rats by the autoimmune method. The paw withdrawal threshold (PWT)
was detected using Von Frey filament. The expressions of the substance P and c
fos in the prostate and spinal L5-S2 segments were determined by
immunohistochemistry followed by analysis of their correlation with CP/CPPS.
RESULTS: Compared with the control rats, the CP/CPPS models showed significantly
decreased PWT (P < 0.05), remarkable prostatic inflammation, enlarged scope of
lesions, and obvious interstitial lymphocytic infiltration (P < 0.05). Both the
expressions of substance P and c-fos were markedly elevated in the prostate and
spinal dorsal horn (L5-S2) of the rat models (P < 0.05), but the expression of
substance P in the prostate exhibited no correlation with that in the spinal cord
(r = 0.099, P = 0.338), nor did that of c-fos (r = 0.027, P = 0.454). CONCLUSION:
The upregulated expressions of substance P and c-fos in the spinal cord L5-S2
sections may be associated with the pain mechanism of CP/CPPS.
PMID- 26442293
TI - [Baicalein enhances the gap junction in the TM4 Sertoli cells of mice].
AB - OBJECTIVE: To investigate the effect of baicalein on the gap junction
intercellular communication (GJIC) in the TM4 Sertoli cells of the mouse testis
and its related mechanism. METHODS: We measured the cytotoxicity of different
concentrations of baicalein on the TM4 Sertoli cells in the mouse testis by MTT,
detected the fluorescence transfer of the TM4 Sertoli cells by parachute assay,
and determined the expression of the protein connexin 43 ( Cx43) in the baicalein
treated cells by Western blot and immunofluorescence assay. RESULTS: Baicalein
produced no obvious cytotoxicity on the TM4 Sertoli cells at the concentration
below 60 umol/L but significantly increased their GJIC at 0-20 umol/L (P < 0.01).
Western blot and immunofluorescence assay showed that 0-20 umol/L baicalein
remarkably elevated the expression of Cx43 in the TM4 cells (P < 0.01) and on the
membrane of the TM4 cells. CONCLUSION: Baicalein at the concentration of 0-20
umol/L can significantly enhance GJIC in mouse TM4 Sertoli cells by increasing
the expression of the Cx43 protein.
PMID- 26442294
TI - [Bone marrow mesenchymal stem cells to repair the reproductive system of male
azoospermia rats].
AB - OBJECTIVE: To study the ability of bone marrow mesenchymal stem cells (BMSCs) to
repair the internal environment of the testis in male azoospermia rats. METHODS:
We established azoospermia models in 22 six-week-old male SD rats by
intraperitoneal injection of busulfan at 20 mg per kg body weight. We
transplanted allogeneic rat BMSCs (rBMSCs) into the testicular seminiferous
tubules of the model rats and, 30 days after transplantation, observed the
composition and structure of the seminiferous tubular cells by HE staining and
detected the expressions of CD44, CD106, and c-kit in the rBMSCs by
immunohistochemistry. RESULTS: The number of epididymal sperm was significantly
reduced in the model rats as compared with the normal controls (P < 0.01). CD44
and CD106, but not c-kit, were expressed in the isolated rBMSCs. At 30 days after
transplantation of rBMSCs, lots of new cells were observed in the seminiferous
tubules, some expressing CD106 and some expressing the germ cell surface marker c
kit. CONCLUSION: BMSCs can transdifferentiate into germ cells and repair the
damaged seminiferous tubules of sterile rats.
PMID- 26442295
TI - [An optimal method for cryopreservation of microamount round spermatids of the
mouse].
AB - OBJECTIVE: To search for an optimal protocol and freezing conditions for the
cryopreservation of microamount round spermatids of the mouse. METHODS: We
compared the survival rates of frozen-thawed microamount round spermatids of the
mouse achieved by vitrification or standard slow freezing with different
concentrations of glycerol (5, 7, or 9%) and different lengths of equilibrium
time (0, 15, 30, 45, or 60 min). RESULTS: Under the conditions of 7% glycerol and
30 min equilibrium, both vitrification and standard slow freezing achieved high
survival rates of spermatids, and the former obtained an even higher rate than
the latter ([72.9 +/- 15.4]% vs [58.2 +/- 17.7]%, P < 0.05). CONCLUSION: A high
rate of frozen-thawed microamount round spermatids of the mouse can be achieved
by vitrification under the conditions of 7% glycerol and 30 min equilibrium.
PMID- 26442296
TI - [Tea polyphenols reduces the apoptosis of spermatogenic cells in rats with
experimental varicocele].
AB - OBJECTIVE: To study the effect of tea polyphenols (TP) on the apoptosis of germ
cells in rats with experimental varicocele. METHODS: Thirty-two adolescent male
Wistar rats were randomly and equally divided into groups A (sham-operation), B
(high-dose TP), C (low-dose TP), and D (experimental left varicocele).
Experimental varicocele was induced by partial ligation of the left renal vein in
the latter three groups of rats. The animals in groups A and D were fed with
normal saline, while those in B and C with TP at 40 and 10 mg per kg per d,
respectively, all for 4 weeks. Then, all the rats were sacrificed and the left
testes harvested for determination of the expression of HIF-1, Bcl-2, Bax, CytC,
and caspase-3 by immunohistochemistry and measurement of the apoptosis index (AI)
of spermatogenic cells. RESULTS: The expression of Bcl-2 was higher in groups B
and C than in D but lower than in A (P < 0.05), and lower in C than in B (P <
0.05). However, the expressions of HIF-1, Bax, CytC, and caspase-3 were lower in
groups B and C than in D but higher than in A (P < 0.05), and higher in C than in
B (P < 0.05). The AI of spermatogenic cells was the lowest in group A, higher in
D than in the other groups but lower in B than in C (P < 0.05). CONCLUSION: TP
can reduce the apoptosis of spermatogenic cells in a dose-dependent manner in
varicocele rats.
PMID- 26442297
TI - [Correlation of TLR2 and TLR4 gene polymorphisms with the susceptibility and
recurrence of condyloma acuminatum].
AB - OBJECTIVE: To explore the correlation of the gene polymorphisms of Toll-like
receptor 2 ( TLR2) and TLR4 with the susceptibility and recurrence of condyloma
acuminatum (CA). METHODS: Using Snapshot, we detected the gene polymorphisms of
TLR2 597(T/C), 1350(T/C), 15607(A/G), and 2258(G/A) and TLR4 896(A/G) and
1196(C/T) in the peripheral blood of 140 CA patients and 105 HPV-negative
controls. We made comparisons between the CA patients and controls as well as
between the cases of recurrent CA and those of non-recurrence at 6 months after
treatment. RESULTS: There were 72, 48, and 20 cases of genotype TT, TC, and CC of
TLR2 597 (T/C), respectively, in the CA patients, as compared with 71, 31, and 3
cases in the controls. The gene frequency of mutant C was 31. 43% in the
patients, significantly higher than 17.62% in the controls (chi2 = 12.04, P <
0.01), and it was 38.68% in the recurrent cases, remarkably higher than 27.01% in
the non-recurrent cases (chi2 = 4.16, P < 0.05). There were 74, 49, and 17 cases
of genotype TT, TC, and CC of TLR2 1350( T/C), respectively, in the CA patients,
as compared with 73, 29, and 3 cases in the controls. The gene frequency of
mutant C was 29. 64% in the patients, significantly higher than 16. 67% in the
controls (chi2 =11.05, P < 0.01), and it was 36.79% in the recurrent cases,
markedly higher than 25. 29% in the non-recurrent cases (chi2 = 4.18, P < 0.05).
There were 44, 66, and 30 cases of genotype AA, AG, and GG of TLR2 15607(A/G),
respectively, in the CA patients, as compared with 26, 58, and 21 cases in the
controls. There was no significant difference in the gene frequencies of mutant G
between the two groups (chi2 = 0.33, P > 0.05). No mutant genes of TLR2 2508
(G/A) or TLR4 896(A/G) and 1196(C/ T) were detected in either the CA patients or
the controls. Linkage disequilibrium analysis showed a tight linkage between TLR2
597 (T/C) and 1350(T/C) (D' = 1, r2 = 0.93). CONCLUSION: TLR2 597(T/C) is tightly
linked to 1350(T/C), which is correlated with both the susceptibility and the
recurrence of condyloma acuminatum.
PMID- 26442298
TI - [A260G and A386G single nucleotide polymorphisms of the DAZL gene are not
correlated with male infertility in the Chinese population of Zhejiang Province].
AB - OBJECTIVE: To assess the association of the A260G and A386G single nucleotide
polymorphisms (SNP) of the DAZL gene with male infertility in the Chinese
population of Zhejiang Province. METHODS: We collected the peripheral blood
samples from 317 idiopathic infertile males with azoospermia or oligozoospermia
and 246 normal fertile men, and genotyped the polymorphic loci of the A260G and
A386G polymorphisms of the DAZL gene using the SNaPshot technique. RESULTS: The
DAZL gene A260G was found genetically polymorphic in the Chinese population of
Zhejiang Province, with the gene frequencies and their distribution consistent to
the Hardy-Weinberg equilibrium. The frequencies of the AA, AG and GG genotypes of
the A260G polymorphism were 92.3%, 7.3%, and 0.4% respectively in the normal
controls and 94.3%, 5.7%, and 0% in the infertile patients, with no statistically
significant differences between the two groups (P = 0.43, OR = 0.78, 95% CI 0.413
1.46). Heterozygosis (AG) of A386G was found in 1 of the control males but not in
the infertile patients, while homozygosis (GG) of A386G was not observed in
either group (P = 0.259, OR = 0.698, 59% CI: 0.374-1.306). CONCLUSION: A260G and
A386G SNPs of the DAZL gene are not associated with spermatogenic failure and
neither represents a molecular marker for the genetic diagnosis of male
infertility in the Chinese population of Zhejiang Province.
PMID- 26442299
TI - [Dynamic changes of the epididymal size after vasectomy: An ultrasonographic
observation].
AB - OBJECTIVE: To investigate the dynamic changes of the epididymal size 1 year after
vasectomy. METHODS: Fifty male volunteers received vasoligation. Before and at 1,
2, 3, 6, and 12 months after operation, we measured the size and detected the
internal echoes of the epididymis using color Doppler ultrasonography. RESULTS:
The bilateral epididymides were both thickened post-operatively in all the 50
cases, with statistically significant differences between the baseline and the
1st month, the 1st and the 2nd month, the 2nd and the 3rd month, or the 3rd and
the 6th month after surgery (all P < 0.01), but not between the 6th and the 12th
month (P > 0.05). CONCLUSION: Within 6 months after vasectomy, the bilateral
epididymides manifested a progressive thickening, but basically restored their
balance of secretion-absorption after 6 months.
PMID- 26442300
TI - [Different scoring systems to evaluate the prognosis of Fournier's gangrene: A
comparative study].
AB - OBJECTIVE: To sum up the experience in diagnosis and treatment of Fournier's
gangrene and find an optimal evaluation tool for its prognosis by comparing
currently used prognostic scoring systems. METHODS: We retrospectively analyzed
16 cases of Fournier's gangrene diagnosed and surgically treated in our hospital
between 2004 and 2012. Using Fournier's Gangrene Severity Index (FGSI), Uludag
Fournier's Gangrene Severity Index (UFGSI), Age-Adjusted Charlson Comorbidity
Index (ACCI), and Surgical Apgar Score (sAPGAR) , we obtained the prognostic
scores of the patients and made comparisons among different scoring systems.
RESULTS: FGSI, UFGSI, ACCI, and sAPGAR were all clinically used scoring systems.
Statistically significant differences were found in the scores of ACCI and UFGSI
but not in those of FGSI and sAPGAR between the death and survival groups, with
the maximum area under the ROC curve and minimum standard error for the ACCI
score. CONCLUSION: Both ACCI and UFGSI are useful for evaluating the prognosis of
Fournier's gangrene. However, ACCI is even better for its higher sensitivity and
specificity and easier clinical collection.
PMID- 26442302
TI - [The volume of residual urine correlates with bladder outlet obstruction and
detrusor contractility in patients with benign prostatic hyperplasia].
AB - OBJECTIVE: To identify the correlation of the volume of residual urine (VRU) with
the severity of bladder outlet obstruction (BOO) and detrusor contractility in
patients with benign prostatic hyperplasia (BPH). METHODS: A total of 152
patients with clinically diagnosed BPH underwent ultrasonography for measurement
of the prostate volume and RVU, free uroflowmetry, and urodynamic examination for
the severity of BOO and detrusor contractility. Using the software SPSS20. 0, we
analyzed the correlation between the ultrasonographic results and urodynamic
parameters and compared the two sample means by the t-test. RESULTS: The prostate
volume was correlated positively with BOO severity (r = 0.432, P < 0.01) and
detrusor contractility (r = 0.343 , P < 0.01) while Qmax negatively with BOO
severity (r = 0.327, P < 0.01) but not significantly with detrusor contractility
(r = 0.123, P > 0.05). VRU showed a significantly negative correlation with
detrusor contractility when > 150 ml (r = -0.490, P < 0.01), even more
significantly when > 300 ml (r = -0.717, P < 0.01), but exhibited no significant
correlation with it when <= 150 ml (r = 0.041, P > 0.05). CONCLUSION: VRU can
somehow predict the detrusor function. For patients with VRU > 150 ml, especially
for those with VRU > 300 ml, the detrusor function should be evaluated and
urodynamic examination is recommended for exact assessment of BOO severity and
detrusor contractility.
PMID- 26442301
TI - [Early diagnosis of prostate cancer by combined use of Trp-p8 expression and PSA
density of the transition zone].
AB - OBJECTIVE: To study the expression of the Trp-p8 protein in the prostate tissue
of the PSA "grey zone" with different PSA density of the transition zone (PSADTZ)
and explore the value of determining Trp-p8 expression and PSADTZ in the early
diagnosis of prostate cancer (PCa). METHODS: This study involved 30 cases of
benign prostatic hyperplasia (BPH) and another 30 cases of PCa with different
PSADTZ values. Using a data imaging and analysis system, we determined the
expression levels of Trp-p8 in BPH and PCa tissues and analyzed their correlation
with PSADTZ. RESULTS: The expression of Trp-p8 was weak or negative in the BPH
but strong in the PCa tissue and even stronger in the PCa tissue with high PSADTZ
(F = 34. 05, P < 0.05). CONCLUSION: The Trp-p8 protein is expressed differently
in BPH and PCa tissues of the PSA " grey zone" and its expression is positively
correlated with PSADTZ. Determination of the Trp-p8 expression and PSADTZ
contributes to the early diagnosis of prostate cancer.
PMID- 26442303
TI - [Decreases of progressive motility, total motility, and acrosin activity of sperm
from oligoasthenoteratospermia males at different time points after sperm
activation].
AB - OBJECTIVE: To investigate the progressive motility, (PR), total motility
(progressive + non-progressive motility, PR + NP), and acrosin activity of sperm
from normal and infertile men at different time points after sperm activation.
METHODS: Based on the 5th edition of the WHO Laboratory Manual for the
Examination and Processing of Human Semen and the results of modified
Papanicolaou staining, we divided the semen samples into groups A (normal, n =
28), B (oligoasthenoteratospermia, n = 30), and C (asthenoteratospermia, n = 32).
At 1, 24, and 48 hours after sperm activation, we detected sperm PR and PR + NP
by CASA and chemical colorimetry, and determined sperm acrosin activity using the
modified Kennedy method. RESULTS: Sperm PR and PR + NP were significantly
decreased in all the three groups at 1-24 hours and even more significantly at 24
48 hours after sperm activation as compared with the baseline (P < 0.05). Sperm
acrosin activity showed remarkable reduction in group A (P = 0. 013) , even more
significant at 1-24 hours than at 24-48 hours after sperm activation, but not in
groups B and C (P = 0.519 and 0.979). CONCLUSION: Sperm PR, PR + NP, and acrosin
activity are all decreased with the extension of time after sperm activation,
each in a specific manner. Examination of sperm acrosin activity should be
applied as a routine tool in the assessment of male fertility.
PMID- 26442305
TI - [Vasectomy does not increase the risk of prostate cancer in Chinese men: A meta
analysis].
AB - OBJECTIVE: To investigate the correlation of vasectomy with the risk of prostate
cancer in Chinese men. METHODS: We systematically searched the databases CNKI,
VIP, Wanfang, PubMed, Embase, and Cochrane Library for the literature relating
the relationship between vasectomy and the risk of prostate cancer in Chinese
males up to December 2014. According to the inclusion and exclusion criteria, two
investigators independently selected the eligible publications, evaluated their
quality, and extracted relevant information, followed by a meta-analysis with the
software STATA 12.0. RESULTS: Nine studies were included in the analysis
involving 1 202 cases of prostate cancer and 4,496 controls. Random-effect model
analysis revealed no statistically significant correlation between vasectomy and
the risk of prostate cancer (OR = 1.05; 95% CI 0.62-1.79), with an obvious
heterogeneity (P < 0.001, I2 = 85.7%). No significant publication bias was found
among the included studies (Egger, P = 0.824; Begg, P = 0.348). CONCLUSION: The
results of our meta-analysis do not support the association of vasectomy with the
increased risk of prostate cancer in Chinese population.
PMID- 26442306
TI - [Hepatocyte growth factor and male reproduction].
AB - The hepatocyte growth factor ( HGF) is a multifunctional growth factor, which
produces multiple biological effects by binding to the c-Met acceptor. This
article reviews the biological properties of HGF, particularly those correlated
with male reproduction, including its abilities to promote testis embryonic
development, spermatogenesis, and testosterone synthesis of Leydig cells. HGF may
provide a new insight into the treatment of male hypogonadism and infertility.
PMID- 26442304
TI - [Protective effect of Liuweidihuang Pills against cellphone electromagnetic
radiation-induced histomorphological abnormality, oxidative injury, and cell
apoptosis in rat testes].
AB - OBJECTIVE: To observe the effect of Liuweidihuang Pills in relieving cellphone
electromagnetic radiation-induced histomorphological abnormality, oxidative
injury, and cell apoptosis in the rat testis. METHODS: Thirty adult male SD rats
were equally randomized into a normal, a radiated, and a Liuweidihuang group, the
animals in the latter two groups exposed to electromagnetic radiation of 900 MHz
cellphone frequency 4 hours a day for 18 days. Meanwhile, the rats in the
Liuweidihuang group were treated with the suspension of Liuweidihuang Pills at 1
ml/100 g body weight and the other rats intragastrically with the equal volume of
purified water. Then all the rats were killed for observation of testicular
histomorphology by routine HE staining, measurement of testicular malondialdehyde
(MDA) and glutathione (GSH) levels by colorimetry, and determination of the
expressions of bax and bcl-2 proteins in the testis tissue by
immunohistochemistry. RESULTS: Compared with the normal controls, the radiated
rats showed obviously loose structure, reduced layers of spermatocytes, and
cavitation in the seminiferous tubules. Significant increases were observed in
the MDA level (P < 0.01) and bax expression (P < 0.01) but decreases in the GSH
level (P < 0.01) and bcl-2 expression (P < 0.01) in the testis issue of the
radiated rats. In comparison with the radiated rats, those of the Liuweidihuang
group exhibited nearly normal testicular structure, significantly lower MDA level
(P < 0.05), bax expression (P < 0.01), and bcl-2 expression (P < 0.01).
CONCLUSION: Liuweidihuang Pills can improve cellphone electromagnetic radiation
induced histomorphological abnormality of the testis tissue and reduce its
oxidative damage and cell apoptosis.
PMID- 26442307
TI - [Induced differentiation of stem cells into androgen-secreting cells].
AB - Leydig cells are the major source of androgens in males. Stem cells can be
induced to differentiate into androgen-secreting Leydig like cells, whose
functions are regulated by the hypothalamus and pituitary, so that they precisely
secret the necessary hormones to maintain physiological function. Therefore, the
establishment of an effective protocol to induce the differentiation of stem
cells into androgen-secreting cells is very helpful for the treatment of
hypogonadism caused by abnormalities of Leydig cells. This review outlines the
recent findings concerning the differentiation of stem cells into androgen
secreting cells.
PMID- 26442308
TI - [Medical and technical means for united circle of evacuation measures in military
medical organisations of the Ministry of Defence].
AB - Experts of the medical service of the Armed Forces carried out an analysis of
capabilities of modern Russian enterprises and their innovative projects
regarding creation of unified means of evacuation of wounded and providing to
them necessary types of emergency care with the use of existing and future
special and regular means of transport for medical evacuation. As a result of the
work of industrial enterprises of the OAO Kazan "Vertoletniy Zavod", "Zarechie",
"Vysota" was created a device for the medical evacuation of severe wounded
patients. The device is designed for medical evacuation of severe wounded
patients from the military medical unit to the site providing comprehensive
medical care with maintenance of vital functions and monitoring of his condition.
Testing was conducted on the products of regular vehicles medical company of one
of the brigades of the Western Military District. The device was presented at the
special tactical exercises the Armed Forces Medical Service "Frontier-2014",
"Innovation Day" of the Defence Ministry in 2014.
PMID- 26442309
TI - [Approaches to development and implementation of the medical information system
for military-medical commission of the multidisciplinary military-medical
organisation].
AB - The current task of the implementation of medical information systems in the
military and medical organizations is an automation of the military-medical
expertise as one of the most important activities. In this regard, noteworthy
experience of the 9th Medical Diagnostic Centre (9th MDC), where on the basis of
medical information system "Interi PROMIS" for the first time was implemented the
automation of the work of military medical commission. The given paper presents
an algorithm for constructing of the information system for the military-medical
examination; detailed description of its elements is given. According to military
servicemen the implementation of the Military Medical Commission (MMC) subsystem
of the medical information system implemented into the 9th MDC has reduced the
time required for the MMC and paperwork, greatly facilitate the work of
physicians and medical specialists on military servicemen examination. This
software can be widely applied in ambulatory and hospital practice, especially in
case of mass military-medical examinations.
PMID- 26442310
TI - [Organisational peculiarities and principles of medical-psychological
rehabilitation of military personnel of special units of the Ministry of
Defence].
AB - The authors presented information about current state of organization of medical
and psychological rehabilitation at sanatorium stage of military servicemen of
special units of the Russian Defense Ministry, information about rehabilitation
treatment techniques, and physical and psychological rehabilitation, natural and
premature medicinal factors.
PMID- 26442311
TI - [Modern methods of inhalation therapy of respiratory diseases].
AB - In pulmonary practice the effectiveness of the therapy depends on a method of
drug delivery. In case of different forms of medications, which can be used for
the treatment of patients with obstructive pulmonary diseases physicians usually
choose inhalants. In this publication authors examines the main aspects of the
use of nebulizers in the treatment of obstructive pulmonary diseases: types of
nebulizers, their capabilities and limitations, indications for inhalation
therapy and drug policy.
PMID- 26442313
TI - [The role of the vaccine prophylaxis of cervical cancer among female military
personnel].
AB - The authors presented results of the study concerning human papillomavirus
infecting of military students of higher military educational institutions of the
Ministry of Defence of the Russian Federation. In the Center for Obstetrics and
Gynaecology of the Kirov Military-Medical Academy was performed a dynamic
examination of 478 female cadets aged 17-25. The high level of high-risk HPV
viruses was revealed during the examination what proves the necessity of
prophylaxis enhancing with the aim to prevent gynecological diseases and
reproductive health promotion. The main ways of cervical cancer prophylaxis are
health education, in-depth medical examination of women with the aim to reveal
and treat gynecological diseases (this medical examination should be carried out
twice a year), primary prevention of cervical cancer by vaccination.
PMID- 26442312
TI - [Treatment of patients with bronchial asthma associated with obesity in a health
resort "Okeanskiy"].
AB - In this paper we assess the efficiency of sanatorium treatment of patients with
bronchial asthma of two different weigh groups: with normal body weight and
obesity. According to the results of clinical examination it was found that in
patients with bronchial asthma and obesity of I-II degree efficiency of
sanatorium treatment is lower in comparison with patients with bronchial asthma
and normal body weight. The use of a standard set of procedures is not enough to
correct the symptoms of asthma in obese patients. Comparative analysis of
clinical symptoms in patients with bronchial asthma with normal body weight and
obesity were differences of up to 50%. The conclusion about the need to develop a
set of techniques to optimize the effectiveness of rehabilitation is given.
PMID- 26442314
TI - [Combined mechanical-cold and mechanical-burn injuries in patients injured in
maritime disasters].
AB - On the basis of analysis of 372 medical histories and total amount of victims
(2691 people) of marine accidents it was revealed that 303 (83.1%) survivors
suffered from combined mechanical-cold injuries, combined two-factor mechanical
burn injuries were diagnosed in 115 of wounded (15.7%), combined three-factor
mechanical-cold-burn injuries were diagnosed in 162 of wounded (22.5%). It was
established that in case of capsizing and shipwrecking chest and abdomen injuries
prevail in wounded (22.4%). Pelvic fractures, injuries of the lower extremities
and spine traumas prevail in wounded evacuated from the crash area after
explosion and fire on the ships (43.3%). The above-mentioned injuries prevail due
to mine-blast nature of injuries. Typical injuries in wounded survived in
maritime disasters are in non-severe combined mechanical-cold, mechanical-burn,
and mechanical-cold-burn injuries, minor and moderate hypothermia, mild burn
injuries and mild carbon monoxide poisoning.
PMID- 26442315
TI - [The set of wearable medical equipment for medical and nursing teams].
AB - The kit is designed in accordance with the list of the first medical aid
procedures and syndromic standards of emergency medical care providing. The kit
contains modern local hemostatic agents, vent tubes, cricothyrotomy, needles to
eliminate pneumothorax, portable oxygen machine, sets for intravenous and
intraosseous infusion therapy, collapsible plastic tires, anti-shock pelvic
girdle, and other medical products and pharmaceuticals. As containers used
backpack and trolley bag on wheels camouflage colours. For the convenience and
safety of the personnel of the vest is designed discharge to be converted in the
body armour.
PMID- 26442316
TI - [The main ways in performing analysis of the activities of medical supply
organizations of the Armed Forces].
AB - Without a complex comprehensive analysis of the activities of medical supply
organizations is impossible to effectively manage the processes of provision of
medical equipment and property, and provide a quality control of finished
products and magistral formulas, technical and metrological provision of medical
services and to render better decisions. In this regard, the article provides a
list of pharmaceutical services (works) provided by medical supply organizations
of the Armed Forces of the Russian Federation and proposes indicators in
assessing their effectiveness. Examples of analysis and assessment of the main
indicators of provided services (works) in absolute values are given. At the same
time, the authors give the ways of solutions aimed at increasing the motivation
of various specialists to improve the quality of performance indicators in the
medical equipment and property support centres of the Ministry of Defense of the
Russian Federation.
PMID- 26442317
TI - [Legal regulation of clinical drug trials for the use in military-medical
organisations].
AB - The authors identified problematic issues of legal regulation of clinical drug
trials for medical use, and proposed possible solutions. It has been established
that the conduction of clinical trials, of medicinal products is based on the
norms of various branches of law embodied in the Constitution of the Russian
Federation, the norms of international law, the Civil Code of the Russian
Federation and federal laws and subordinate legislations regulating health and
pharmaceutical activity. According to the authors, the norms of bioethics can be
attributed to the sources of legal doctrine. It is proposed to oblige executives
of clinical trials to make a report about effectiveness and safety of drugs and
pass the results to the customer, in his/her turn the customer is obliged to
accept the results of these trials and pay for them.
PMID- 26442318
TI - [Medical Service of the Estonian Defense Forces].
AB - The article is a brief description of the current state of the Estonian Defense
Forces medical service and is based on the study of the open access foreign
sources. At the beginning, the general information about Estonia, its Defense
Forces, and their medical service is presented. Then the medical service
particular features are described with more detail, namely, the organization of
the inpatient and outpatient treatment, medical supply, scientific research,
combat medicine, medical staff education and training, medical service personnel
income.
PMID- 26442320
TI - [To the 80th anniversary of the 637th center of the state sanitary and
epidemiological surveillance].
AB - In March 2015 marked the 80th anniversary of the creation of the 637th Center of
State Sanitary and Epidemiological Surveillance. The date of establishment of the
Centre is rooted in the pre-war period, when sanitary-epidemiological
laboratories of the Black Sea Fleet were organized as a scientific and
methodological institution. During the Great Patriotic War, as well as during the
early postwar period, the staff of the Centre carried out valuable work on
provision of sanitary and epidemiological welfare of the Black Sea Fleet. Later,
soldiers of the Center participated in the aftermath of the Chernobyl accident,
fulfilling their international duty in the Democratic Republic of Afghanistan, on
the island of Dahlak, as well as in the Chechen Republic during the anti
terrorist operation. During its existence, the Centre repeatedly reorganized and
is now an institution that successfully solves the problem of ensuring sanitary
and epidemiological welfare of the troops in the area of responsibility.
PMID- 26442319
TI - [The contribution of the Archive of the Military Medical Museum in summarizing
the experience of the Great Patriotic War].
AB - During 70 years of existence of the Military Medical Museum one of its main goals
was to create an archive of military medical documents, the formation of his
ideology and collecting funds, saving and promotion of unique materials related
to the history of Russia, feat of arms Defenders of the Fatherland in the wars of
the XX century. Creating a military medical museum archive was conceived in the
beginning of the Great Patriotic War by leading figures of the military medicine-
E.I.Smirnov, S.M.Bagdasaryan, V.N.Shevkunenko, A.N.Maksimenkov, who offered to
collect all materials about the work of physicians at the front and in the rear,
to consider the archive as a base for scientific works on the history of the
military health care. Today the archive was removed from the Army Medical Museum
and now it is a branch of the Central Archive of the Ministry of Defence of the
Russian Federation (military medical records). His staff keeps the traditions
established by predecessors and use in their activities a wealth of experience
and background research.
PMID- 26442321
TI - [Dual-wavelenght optoelectronic sensor for monitoring uric acid concentration in
dialysis fluid].
PMID- 26442322
TI - [Optoelectronic device for diagnosis of esophagus dysfunction].
PMID- 26442323
TI - [Scanning probe nanotomograph: peculiarities of technical solutions for analysis
of biomedical materials at low temperatures].
PMID- 26442324
TI - [Modern methods for measurement of blood coagulation parameters].
PMID- 26442325
TI - [Laboratory equipment for studying cell reaction to high-voltage pulsed electric
field].
PMID- 26442326
TI - [Assessment of mechanical characteristics of biological tissue in cases of
surface modification with the linearIy chained carbon].
PMID- 26442327
TI - [Improvement of load capacity of piezoceramic emitters of ultrasonic devices used
in traumatology and surgery].
PMID- 26442328
TI - [Calculation of coefficients of anisotropy and symmetry of cornea nerve
orientation based on automated recognition of digital confocal images].
PMID- 26442329
TI - [A device for noninvasive measurement of the frequency of action potentials of
single motor units].
PMID- 26442330
TI - [Preclinical tests of dioxidine as a decontaminating agent for cardiac valve
bioimplants].
PMID- 26442331
TI - [Automation of recognition of cerebral stroke boundaries based on the threshold
processing of magnetic resonance images].
PMID- 26442332
TI - [The effect of angular displacement of coils on the efficiency of transcutaneous
wireless energy transfer using induction coupling].
PMID- 26442333
TI - [The effect of spectral composition of probing signal on the results of
bioimpedance measurement in biological objects].
PMID- 26442334
TI - [Development of an automated device for knee joint mechanotherapy].
PMID- 26442335
TI - [Classification and structure of biomedical computer-aided design systems].
PMID- 26442336
TI - [Simulation of processes of generation of peripheral arterial blood pulsation].
PMID- 26442337
TI - From Sound to Significance: Exploring the Mechanisms Underlying Emotional
Reactions to Music.
AB - A common approach to studying emotional reactions to music is to attempt to
obtain direct links between musical surface features such as tempo and a
listener's responses. However, such an analysis ultimately fails to explain why
emotions are aroused in the listener. In this article we explore an alternative
approach, which aims to account for musical emotions in terms of a set of
psychological mechanisms that are activated by different types of information in
a musical event. This approach was tested in 4 experiments that manipulated 4
mechanisms (brain stem reflex, contagion, episodic memory, musical expectancy) by
selecting existing musical pieces that featured information relevant for each
mechanism. The excerpts were played to 60 listeners, who were asked to rate their
felt emotions on 15 scales. Skin conductance levels and facial expressions were
measured, and listeners reported subjective impressions of relevance to specific
mechanisms. Results indicated that the target mechanism conditions evoked
emotions largely as predicted by a multimechanism framework and that mostly
similar effects occurred across the experiments that included different pieces of
music. We conclude that a satisfactory account of musical emotions requires
consideration of how musical features and responses are mediated by a range of
underlying mechanisms.
PMID- 26442338
TI - Emotion in Painting and Art Installations.
AB - Paintings are static 2-dimensional images with limited narrative means. On the
basis of a critical analysis of the relevant laboratory scaling studies, museum
studies, and neuroaesthetic work, the article reaches a negative conclusion about
most paintings' ability to engage sufficiently with general viewers' associative
memory systems, so as to lead to identification and empathy, and induce
fundamental psychobiological emotions. In contrast, designers of art
installations can draw on subtle combinations of several classes of stimulus
properties with psychological significance subsumable under the classical concept
of the sublime (physical grandeur, rarity, an association with beauty and with
biologically significant outcomes), so that some installations may induce the
peak aesthetic emotional response, aesthetic awe--as defined in Aesthetic Trinity
Theory (Konecni, 2005, 2011), along with the states of being moved and
physiological thrills. The approach also involves an analytical skepticism about
emotivism, defined as a culturological proclivity for unnecessary insertion of
emotion into accounts of mental life and behavior, especially in the arts.
Implications for the role of emotion theory in empirical aesthetics are examined.
PMID- 26442339
TI - The Automatic Activation of Emotion and Emotion-Laden Words: Evidence from a
Masked and Unmasked Priming Paradigm.
AB - A primed lexical decision task (LDT) was used to determine whether emotion (e.g.,
love, fear) and emotion-laden (e.g., puppy, hospital) word processing differs,
both explicitly and implicitly. Previous experiments have investigated how
emotion word processing differs from both abstract and concrete word processing
(Altarriba & Bauer, 2004; Altarriba, Bauer, & Benvenuto, 1999). To assess for
differences between emotion and emotion-laden word processing, 2 experiments were
conducted, the first assessing explicit processing (using an unmasked LDT) and
the second assessing automatic processing (using a masked LDT). The prediction
that semantic priming would differ between emotion word pairs and emotion-laden
word pairs was confirmed in both experiments, with shorter response times for
emotion targets and greater priming effects for emotion word pairs than for
emotion-laden word pairs. The role of valence is discussed, emphasizing the ways
valence affects the speed with which these words are accessed and processed.
PMID- 26442340
TI - Interference Resolution in Emotional Working Memory as a Function of Alexithymia.
AB - Although alexithymia is recognized as a set of traitlike deficits in emotion
processing, research suggests there are concomitant cognitive issues as well,
including what appears to be an unusual pattern of enhanced working memory (WM)
despite broader executive dysfunction. It is unknown whether this enhancement
includes the executive elements of WM and whether executive control of WM in
alexithymia differs for emotional and neutral stimuli. This study examined how
alexithymia moderates patterns of interference resolution in WM with valenced and
nonvalenced stimuli. Participants (N = 93) completed the Toronto Alexithymia
Scale and a recency probes WM task containing positive, negative, and neutral
stimuli, with some trials containing proactive interference from previous trials.
The reaction time difference between interference and noninterference trials
indexed degree of interference resolution. Toronto Alexithymia Scale score
moderated a within-subject effect such that, when valenced probes were used,
there was less proactive interference in the positive relative to negative
valence condition; this valence-based interference discrepancy was significant
for a subset of highly alexithymic participants. Alexithymia did not moderate
proactive interference to negative or neutral stimuli or accuracy of responses.
These results suggest that, although alexithymia does not influence executive
control in WM for nonemotional items, alexithymic people demonstrate an
idiosyncratic response to positive stimuli that might indicate blunted
reactivity.
PMID- 26442341
TI - Reducing Misanthropic Memory Through Self-Awareness: Reducing Bias.
AB - Two experiments investigated the influence of self-awareness on misanthropic
recall. Misanthropic recall is the tendency to recall more negative behaviors
dispositionally attributed and positive behaviors situationally attributed than
negative behaviors situationally attributed and positive behaviors
dispositionally attributed. It was hypothesized that when one is self-aware, more
systematic information processing would occur, thereby reducing misanthropic
memory and influencing attitudinal judgments. The first experiment used a mirror
and the second experiment used a live video to induce self-awareness.
Participants were asked to form an impression of a group. The results of both
experiments replicated the previously found pattern of misanthropic memory for
non-self-aware participants (Ybarra & Stephan, 1996), and revealed less
misanthropic recall bias in self-aware participants.
PMID- 26442342
TI - Callosal Sensitivity to Short-Range Stimulus Orientation and Long-Range Stimulus
Context Orientation: Tachistoscopic Evidence.
AB - To study local-global relationships in interhemispheric interactions,
tachistoscopically presented pairs of lines (1.15 degrees) were compared for
their relative orientation by 48 neurotypical adults. Orientations of line
stimuli (local aspect of the task) were vertical, horizontal, forward slash or
backslash, as were those of the interstimulus axes. The latter created a global
context that could influence line discrimination. Stimulus pairs were presented
within a field (not requiring callosal participation for line orientation
comparison) or one on each side of the visual field meridian (requiring callosal
participation). The primary purpose of the design was to determine whether local
or global violations of stimulus "homotopy" across the meridian would impose
costs of interhemispheric integration. The rationale for this expectation is that
the fiber projection of the corpus callosum is highly symmetric across the
midsagittal plane (i.e., homotopic). The expected "callosal homotopy" effect was
significantly upheld as a whole but broke down or became extravagant in certain
specific conditions, with specific costs of interhemispheric integration varying
from null to a highly significant 20-ms as a function of interactions of
interstimulus and stimulus orientations. The corpus callosum seems to be
particularly sensitive to local stimulus orientation in interaction with long
range stimulus context orientation.
PMID- 26442343
TI - Towards a Mechanistic Understanding of the Effects of Body Posture on Facial
Emotion Categorization.
AB - This study investigated the causes of the face-body congruence effect (FBCE),
which refers to the advantage in performance when participants are asked to
categorize emotional faces compounded with emotional matching body postures
(congruent) compared with incongruent face-body compound stimuli (body postures
mismatching the facial emotions). Experiment 1 showed that manipulations aiming
to alter holistic processing significantly reduced the FBCE. In particular, the
disruption of holistic processing affected significantly the performance for
congruent composites. However, no effect was obtained on the incongruent stimuli.
In Experiment 2, the inversion manipulation showed a clear disadvantage for
incongruent stimuli brought by the disruption of the single feature orientation
information. Thus, we found confirmation of the different processing involved in
perceiving congruent and incongruent stimuli. Finally, Experiment 3 confirmed
that we are able to reduce entirely the FBCE when the orientation of the units
(the face and the body) constituting the incongruent composites is matched.
PMID- 26442344
TI - Cognitive Processing of Scrambled Faces: Effects of Instructions and Task.
AB - The present study tests Rakover and Cahlon's (2013) face-checking model, which
grades 7 regular and scrambled faces on a scale of similarity to an upright
regular face, by predicting the results of 2 experiments in upright and inverted
orientations: Experiment 1, which uses the interest choice task (to choose from a
pair of faces the one most interesting), and Experiment 2, which uses the old/new
recognition task. The main results of these 2 experiments show that in comparison
to Rakover and Cahlon's (2013) findings, the face-checking model preserves its
ability to predict satisfactorily the order of the 7 faces in the 2 experiments
especially in the upright orientation; however, the model's success in making
accurate point predictions is reduced significantly in both the upright and the
inverted orientations.
PMID- 26442345
TI - The Evolution of The American Journal of Psychology 1, 1887-1903: A Network
Investigation.
AB - The American Journal of Psychology (AJP) was the first academic journal in the
United States dedicated to the "new" scientific form of the discipline. But where
did the journal's founding owner/editor, G. Stanley Hall, find the
"psychologists" he needed to fill the pages of such a venture 1887, when he was
still virtually the only professor of psychology in the country? To investigate
this question we used the substantive vocabularies of every full article
published in AJP's first 14 volumes to generate networks of verbally similar
articles. These networks reveal the variety of research communities that Hall
drew on to launch and support the journal. Three separate networks, corresponding
to 3 successive time blocks, show how Hall's constellation of participating
research communities changed over AJP's first 17 years. Many of these communities
started with rather nebulous boundaries but soon began to differentiate into
groups of more distinct specialties. Some topics declined over time, but new ones
regularly appeared to replace them. We sketch a quasievolutionary model to
describe the intellectual ecology of AJP's early years.
PMID- 26442346
TI - It's about the journey.
PMID- 26442347
TI - Guitar man.
PMID- 26442349
TI - Nontraditional path.
PMID- 26442348
TI - Clinical hiatus, then what?
PMID- 26442350
TI - New designation, new opportunity.
PMID- 26442351
TI - TURNING POINTS.
PMID- 26442352
TI - WITH A LITTLE HELP. Why all the studying matters.
PMID- 26442353
TI - CLINICAL NOTE: MS. S, 25F. Questioning those giving career advice.
PMID- 26442354
TI - Rose. When things don't go as planned.
PMID- 26442355
TI - CLEARING THE AIR. Looking back on a public health battle.
PMID- 26442356
TI - The A, B, C, Ds of Opioid Prescribing for People Living with Cancer.
AB - This articles reviews guidelines for safe and effective opioid prescribing by
primary care physicians for people living with cancer-related pain. It also
offers tips for community clinicians on initiating, titrating and managing
opioids for pain management.
PMID- 26442357
TI - Recent Outbreaks of Meningococcal Disease among Men Who Have Sex with Men.
AB - Meningococcal disease outbreaks recently have occurred in several U.S. cities
among men who are HIV-infected and who have had sex with other men. This article
describes the first similar case of meningococcal meningitis serogroup C in
Minnesota, which was confirmed this summer. It also offers vaccination guidance
for physicians who care for patients who may be at high risk for the disease.
PMID- 26442359
TI - SERIOUS GAMES FOR HEALTH: AN INTRODUCTION TO THE SYMPOSIUM.
PMID- 26442358
TI - Think Globally, Act Locally: Diagnosis and Management of Latent Tuberculosis in
Minnesota's Foreign-Born Population.
AB - Although the overall incidence and prevalence of tuberculosis (TB) is relatively
low in the United States, the disease remains a significant problem among certain
populations. Refugees and immigrants migrating from endemic countries are
especially at risk for TB, and in Minnesota the majority of cases are found in
this population. Given that the vast majority of these cases are caused by
reactivated latent infection rather than primary infection, the key to disease
control and prevention is the successful diagnosis and management of latent TB in
immigrants and refugees from endemic areas. This article details the appropriate
approach to screening, diagnosis and management of latent TB in the hope that all
physicians are better equipped to aid our state's foreign-born population and
improve public health.
PMID- 26442360
TI - CREATING A SERIOUS GAME FOR HEALTH.
AB - The prevalence of chronic illnesses continues to increase as does the cost of
such care. Teaching self-management skills is more effective than solely
providing information and teaching technical skills at improving health outcomes.
Serious games for health provide an opportunity to support learning and health
related behavior change using messages and experiences in an engaging and
entertaining format. We developed eSMART-HD with the intention of improving
interactions between patients with chronic disorders and their health care
providers. This paper describes the factors that we considered when creating
eSMART-HD, a serious game for health.
PMID- 26442361
TI - WAIT, WON'T! WANT: BARRIERS TO HEALTH CARE AS PERCEIVED BY MEDICALLY AND SOCIALLY
DISENFRANCHISED COMMUNITIES.
AB - OBJECTIVES: We explored barriers to healthcare as perceived by members of
medically and socially disenfranchised communities. METHODS: We conducted focus
groups with 28 women and 32 men from Northeast Ohio who identified themselves as
African-American, Hispanic/Latino, lesbian/gay/bisexual/transgendered, and/or
Russian immigrant. RESULTS: Participants described their experiences of waiting,
things they won't tolerate, when they won't participate, and what they want from
providers. They described behaviors, actions and relationship characteristics
that they want from their providers and characteristics that they prefer in
health systems. CONCLUSIONS: The themes of Wait, Won't, and Want have healthcare
practice and policy implications. Patient-provider interactions are known to be
significant determinants of healthcare outcomes and these exploratory findings
suggest that they might also affect patient self-management strategies. Future
efforts should focus on developing and testing patient-centered strategies that
address the themes identified to increase engagement to increase self-management
of health.
PMID- 26442362
TI - BE HEARD: HEALTHCARE PERSPECTIVES FROM MEDICALLY AND SOCIALLY DISENFRANCHISED
COMMUNITIES.
PMID- 26442363
TI - ENHANCING COMMUNICATION BETWEEN PATIENTS AND HEALTHCARE PROVIDERS: SBAR3.
PMID- 26442364
TI - IMPACT OF A SERIOUS GAME FOR HEALTH ON CHRONIC DISEASE SELF-MANAGEMENT:
PRELIMINARY EFFICACY AMONG COMMUNITY DWELLING ADULTS WITH HYPERTENSION.
AB - Most Americans will acquire a chronic disease during their lifetime. One of the
most prevalent chronic diseases that affect Americans is hypertension (HTN).
Despite the known comorbidities and increased mortality rate associated with
uncontrolled HTN, most community dwelling adults with HTN do not have sufficient
blood pressure control Therefore, the aim of this article is to report the
preliminary efficacy of a serious game for health to enhance blood pressure
control among community dwelling adults with HTN. A nonprobability sample of 116
community dwelling adults with HTN participated in this nonblinded, randomized
controlled trial. Participants were randomly assigned to: (1) an intervention arm
that consisted of four exposures to a serious game for health known as eSMART-HD;
or (2) an attentional control arm that compromised of four exposures to screen
based HTN education. The primary outcome measure for this trial was blood
pressure reduction over a four month observational period. In this study,
baseline characteristics and blood pressure measurements were similar between
participants in each study arm. There was no significant between-group difference
in blood pressure reduction over time. However, there were significant within
group reductions in systolic and diastolic blood pressures across time among
favoring participants exposed to eSMART-HD. This study establishes the
preliminary efficacy of eSMART-HD that can be easily administered to community
dwelling adults and facilitate clinically significant reductions in systolic and
diastolic blood pressures. Future studies should assess the influential
components of this promising serious game for health (eSMART-HD) combined with
medication management in larger and more diverse samples of community dwelling
adults with HTN.
PMID- 26442365
TI - EMPOWERING PATIENTS TO BECOME BETTER PARTNERS.
PMID- 26442366
TI - [Relation between Injury Time and the Expression of COX6C mRNA in Skeletal Muscle
of Rats after Contusion].
AB - OBJECTIVE: To investigate the relation between injury time and the expression of
cytochrome c oxidase subunit VIc (COX6C) mRNA in skeletal muscle of rat after
contusion. METHODS: A total of fifty-four SD rats were divided into the control
group and the contusion groups (0.5, 1, 6, 12, 18, 24, 30, and 36 h after
contusion), randomly. The contusion model was established by free fall drop of
gravity hammer. At corresponding time point after contusion, the regular
histology was examined and expression level of COX6C mRNA was tested by real-time
PCR after extraction of total RNA from the tissues. RESULTS: The main
pathological features of 6 h after injury included edema and hemorrhage in
myocytes with no inflammatory cells found. After 6 hours, the findings included
myocyte degeneration and necrosis, inflammatory cells infiltration, and fibrous
connective tissue proliferation in the contused zone. The expression level of
COX6C mRNA was higher than that of the control group within 6 h after contusion.
The expression level was lower than that of the control group from 6-36 h after
contusion. CONCLUSION: The level of COX6C mRNA expresses in a regular way after
contusion. It may be useful for estimating wound age in combination with the
results of pathological features.
PMID- 26442367
TI - [Changes of Serum IgE and Tryptase in Anaphylactic Shock Rats].
AB - OJECTIVE: To explore the changes of serum IgE and tryptase caused by anaphylactic
shock rats and discuss the relation to PMI and preservative environment of corpse
and specimen. METHODS: Rats were used for establishing anaphylactic shock models
and randomly divided into room temperature group, refrigeration group, frozen
group, manual hemolysis group, specimen preservation group. And the control group
was also established. The blood samples were collected after rats were
sacrificed. The degree of hemolysis was graded according to the color of the
upper layer of the serum. The mass concentration of IgE and tryptase in each
group was detected by ELISA. RESULTS: The levels of serum IgE and tryptase in
anaphylactic shock dead rats were higher than that of the control group. Room
temperature and frozen made obviously differences on the levels of serum IgE and
tryptase with various PMI. The levels of serum IgE and tryptase in refrigeration
group showed relatively stable. The levels of serum tryptase and IgE were
elevated with differently increasing hemolysis. The levels of serum IgE and
tryptase showed no obvious changes during the specimen kept under different
temperature conditions for 25 days. CONCLUSION: Serum IgE and tryptase obviously
increased in anaphylactic shock rats. However, the levels were influenced by PMI
and environmental temperature, especially under the conditions of room
temperature and frozen.
PMID- 26442368
TI - [Effect of Heroin on DLG4 Expression in Hippocampus, Amygdala and Frontal Cortex
of Rats].
AB - OBJECTIVE: To observe the expression of discs large homolog 4 (DLG4) protein in
hippocampus, amygdala and frontal cortex of rats and evaluate postsynaptic
density in heroin dependence. METHODS: The rat heroin dependent model was
established by increasing intraperitoneal injection of heroin. DLG4 proteins in
hippocampus, amygdala and frontal cortex of heroin dependent 9, 18, 36 days rats
were detected with immunohistochemical staining and compared with that in the
control group. RESULTS: DLG4 proteins in hippocampus, amygdala and frontal cortex
were gradually reduced with extension of heroin dependent time. CONCLUSION:
Heroin dependence can affect postsynaptic density of hippocampus, amygdala and
frontal cortex. The changes become more apparent with extension of heroin
dependence time.
PMID- 26442369
TI - [Diagnostic Significance of BAT in Anaphylaxis to Non-ionic Contrast Media].
AB - OBJECTIVE: To investigate the diagnostic significance of basophil activation test
(BAT) in anaphylaxis to non-ionic contrast media through testing the content of
CD63, mast cell-carboxypeptidase A3 (MC-CPA3), and terminal complement complex
SC5b-9 of the individuals by testing their levels in the normal immune group and
the anaphylaxis groups to beta-lactam drugs and non -ionic contrast media.
METHODS: The CD63 expression of basophilic granulocyte in blood was detected by
flow cytometry. The levels of MC-CPA3 in blood serum and SC5b-9 in blood plasma
were detected by ELISA. RESULTS: The CD63 expression of basophilic granulocyte in
blood, the levels of MC-CPA3 and SC5b-9 of anaphylaxis to non-ionic contrast
media and beta-lactam drugs were significantly higher than that in normal immune
group (P < 0.05). CONCLUSION: There is activation of basophilic granulocytes,
mast cells and complement system in anaphylaxis to non-ionic contrast media. BAT
can be used to diagnose the anaphylaxis to non-ionic contrast media.
PMID- 26442370
TI - [Postmortem MSCT Analysis and Identification of Fall from Height: One Case
Report].
AB - OBJECTIVE: To explore the application value of postmortem multi-slice spiral
computed tomography (MSCT) in cases of fall from height through observing and
analyzing the injury features of the fall and reconstructing the process of the
fall based on the the above procedure. METHODS: One real fatal case due to fall
from height was fully examined using MSCT and three-dimensional reconstruction
technique. Analyzing the manner and cause of death through combination of MSCT
and systemic autopsy was also implemented. The differences between autopsy and
MSCT in getting information of injuries were compared. RESULTS: Fractures
involving multiple body regions and liver rupture were found through MSCT and
three-dimensional reconstruction. The autopsy got the same results with
imageological examination. The case of death was deduced to be fall leading to
systemic polytrauma. CONCLUSION: Application of MSCT can be used as the
complimentary for traditional autopsy in the analysis of injury manner of fall
from height.
PMID- 26442371
TI - [Relation between Body Height and Combined Length of Manubrium and Mesosternum of
Sternum Measured by CT-VRT in Southwest Han Population].
AB - OBJECTIVE: To establish the linear regression equation between body height and
combined length of manubrium and mesostenum of sternum measured by CT volume
rendering technique (CT-VRT) in southwest Han population. METHODS: One hundred
and sixty subjects, including 80 males and 80 females were selected from
southwest Han population for routine CT-VRT (reconstruction thickness 1 mm)
examination. The lengths of both manubrium and mesosternum were recorded, and the
combined length of manubrium and mesosternum was equal to the algebraic sum of
them. The sex-specific linear regression equations between the combined length of
manubrium and mesosternum and the real body height of each subject were deduced.
RESULTS: The sex-specific simple linear regression equations between the combined
length of manubrium and mesostenum (x3) and body height (y) were established
(male: y = 135.000+2.118 x3 and female: y = 120.790+2.808 x3). Both equations
showed statistical significance (P < 0.05) with a 100% predictive accuracy.
CONCLUSION: CT-VRT is an effective method for measurement of the index of
sternum. The combined length of manubrium and mesosternum from CT-VRT can be used
for body height estimation in southwest Han population.
PMID- 26442372
TI - [Analysis of GHB and Its Precursors in Urine and Their Forensic Application].
AB - OBJECTIVE: To establish the method to analyze gamma-hydroxybutyric acid (GHB) and
its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) in urine
through LC-MS/MS and provide evidence for related cases. METHODS: GHB-d6 and MOR
d3 were used as the internal standard. The urine sample was separated by LC after
protein precipitation with methanol. The electrospray ion source was for
ionization. Each compound was detected through multiple-reaction monitoring (MRM)
mode. RESULTS: The limits of detection of GHB and its precursors 1,4-BD and GBL
were 0.1, 0.1 and 2 MUg/mL. The accuracy was 87.6%-98.1%. The intra-day and inter
day precisions were less than 15% and matrix effects were higher than 80%.
CONCLUSION: The method is high sensitive, simple, rapid, specific and with high
reliability. This study has provided technical support and basic data for
forensic cases involving GHB.
PMID- 26442373
TI - [Forensic Analysis of Melamine-tainted Milk Powder Poisoning: Six Fatal Cases].
AB - OBJECTIVE: To analyze the medical records of poisoned children to provide
references for the forensic identification of melamine-tainted milk powder
poisoning. METHODS: Medical records of six fatal cases of consuming some brand
melamine-tainted milk powder were studied, specifically the poisoning symptoms,
medical imaging, blood biochemical tests, treatment and prognosis. RESULTS: The
major medical problems of these eight-month sick infants were urinary tract
obstruction caused by urinary tract calculi. The poisoned infants developed
oliguria, anuria and other symptoms, eventually, acute renal failure or other
complications leaded to death. The serum BUN and Cr abnormally increased.
CONCLUSION: By considering the toxicological effects of melamine, it was
concluded that the deaths of these sick infants were related to the melamine
poisoning.
PMID- 26442374
TI - [Analysis of 59 Anaphylactic Death Cases].
AB - OBJECTIVE: To analyze the cases of anaphylactic death cases and explore the
standards of judicial expertise of anaphylactic death for providing evidence for
judicial expertise. METHODS: Fifty-nine cases death due to allergic reaction in
Shanghai were collected. And details of medical history, clinical manifestation
of anaphylactic reaction and postmortem examination findings were reviewed for
all cases. RESULTS: In the 59 cases, there were 58 cases died from drug allergy,
including 77.6% of them were antibiotics. The rates of treating in standard
hospital and illegal clinic were 37.3% and 61.0%, respectively. The allergic
symptoms were dyspnea and facial cyanosis. The time from contacting allergens to
death ranged from 1 min to 3 d. The concentration of total serum IgE ranged from
50 to 576.92 IU/mL. The results of clinical manifestation and pathological
anatomy had obviously changes. CONCLUSION: Based on the exclusion of all other
cause of death and synthetically analysis of details of cases, medical history,
clinical manifestation and anatomy, the conclusion of anaphylactic death can
reached. The details of cases including clinical history, exposure to allergens,
and clinical manifestation play an important role in diagnosis of anaphylactic
death.
PMID- 26442375
TI - [Genetic Polymorphisms of 21 Autosomal STR Loci of Fujian Han Population].
AB - OBJECTIVE: To investigate the genetic polymorphisms of 21 autosomal STR loci of
Fujian Han population and evaluate the forensic application value of GlobalFiler
Express kit. METHODS: Amplified with GlobalFiler Express kit, DNA samples were
obtained from 741 unrelated individuals of Fujian Han population. The population
genetics parameters of 21 autosomal STR loci were calculated. RESULTS: The 21
autosomal STR loci were found to be no deviation from Hardy-Weinberg
equilibration (P > 0.05) and relatively abundant in high polymorphism.
Heterozygosity ranged from 0.589 to 0.914, power of discrimination ranged from
0.754 to 0.992, polymorphic information content ranged from 0.520 to 0.940, and
power of exclusion ranged from 0.278 to 0.825. The SE33 locus was the highest
degree in polymorphism. CONCLUSION: The 21 STR loci of GlobalFiler Express kit
have high value in discrimination power and can be useful in personal
identification and paternity test in Fujian Han population.
PMID- 26442376
TI - [Research Progress of Event-related Potential in Mild Cognitive Impairment].
AB - Mild cognitive impairment caused by craniocerebral trauma is the key points and
difficulties in judicial authentication. This article has comparative analysis of
each mode of event-related potential (classical Oddball, Eriksen flanker task and
so on), which can provide a more objective method for such craniocerebral trauma
cases in clinical forensic judicial authentication.
PMID- 26442377
TI - [Development and Application of Metabonomics in Forensic Toxicology].
AB - Metabonomics is an important branch of system biology following the development
of genomics, transcriptomics and proteomics. It can perform high-throughput
detection and data processing with multiple parameters, potentially enabling the
identification and quantification of all small metabolites in a biological
system. It can be used to provide comprehensive information on the toxicity
effects, toxicological mechanisms and biomarkers, sensitively finding the unusual
metabolic changes caused by poison. This article mainly reviews application of
metabonomics in toxicological studies of abused drugs, pesticides, poisonous
plants and poisonous animals, and also illustrates the new direction of forensic
toxicology research.
PMID- 26442379
TI - How to Respond to "Inappropriate Invitations".
PMID- 26442378
TI - [Research Progress on Forensic Entomotoxicology].
AB - Forensic entomotoxicology is a branch of forensic medicine, which applies
entomology, toxicology and other related studies to solve the poisoning cases. It
has an obvious advantage in the investigation on poisoning death. Based on the
expounding definition and research of entomotoxicology, this paper reviews
research progress and application value in some aspects of forensic medicine,
such as the effects of drugs/toxins on the growth and development of
sarcosaphagous insects and the qualitative and quantitative analysis of the
drugs/toxins in the poisoned body tissue.
PMID- 26442380
TI - What's Past is Prologue.
PMID- 26442381
TI - Dinner with a Nobel Laureate.
PMID- 26442382
TI - Fellows of the American Physiological Society Inaugural Class.
PMID- 26442383
TI - S&R Foundation 15th Anniversary.
PMID- 26442384
TI - Meeting of the Minds: Send Your Stories.
PMID- 26442385
TI - Letter to Hiroko Nishimura.
PMID- 26442387
TI - COMPLICATIONS FOLLOWING DIFFERENT TECHNIQUES OF ONE-LUNG VENTILATION.
PMID- 26442386
TI - Letter to Hiroko Nishimura.
PMID- 26442388
TI - ANESTHETIC MANAGEMENT FOR DRUG INDUCED SLEEP ENDOSCOPY.
PMID- 26442389
TI - PERIOPERATIVE PAIN CONTROL IN GASTROINTESTINAL SURGERY.
AB - Perioperative pain control in the setting of gastrointestinal surgery presents
unique challenges for the clinician, including the incidence of ileus and its
potential exacerbation by analgesics, large incisions, patient characteristics
and a wide variety of other factors. At the same time, optimizing postoperative
pain control is of key significance in this patient population and has
implications for both medical and surgical outcomes, length of hospital stay and
associated costs and risks of developing chronic postsurgical pain. Data from
recent clinical trials and other studies have highlighted the impact of specific
surgical and anesthetic techniques on post-operative pain for several types of
abdominal surgeries, including pancreatoduodenectomy, hepatectomy, gastric
bypass, cholecystectomy, colectomy, and appendectomy. The management of pain may
be optimized through the multidisciplinary and concerted efforts between
clinicians involved in the perioperative care of patients undergoing
gastrointestinal surgery.
PMID- 26442390
TI - RESIDENT IMPLEMENTATION OF THE 2007 ACC/AHA GUIDELINES ON PREOPERATIVE CARDIAC
EVALUATION IN NON-CARDIAC SURGERY PATIENTS: IS CLINICAL EXPERIENCE ENOUGH?
AB - BACKGROUND: Preoperative evaluation of surgical patients is important, as
perioperative complications are associated with increased mortality. Specialties
including anesthesiology, internal medicine, cardiology, and surgery are involved
in the evaluation and management of these patients. This institutional study
investigated the residents' knowledge of the 2007 American College of
Cardiology/American Heart Association (ACC/AHA) guidelines on perioperative
evaluation of patients undergoing non-cardiac surgery. METHODS: This pilot study
used a web-based survey questionnaire to assess resident's knowledge of the 2007
ACC/AHA guidelines through individual steps and corresponding branch point(s) in
twelve clinical scenarios. Additionally, residents were asked if they were aware
of, or if they had received lectures on ACC/AHA guidelines. Staff
anesthesiologists with training in cardiac and intensive care medicine validated
the scenarios. RESULTS: A total of 104 resident participants were surveyed
including 35 anesthesiology residents, 41 internal medicine residents, 20 surgery
residents, and 8 cardiology fellows. Awareness of the 2007 ACC/AHA guidelines by
specialty was: anesthesiology (85%), internal medicine (97.6%), cardiology
(100%), and surgery (70%). Only 54.3% of anesthesiology, 31.7% of internal
medicine, 100% of cardiology, and 10% of surgery residents stated they received
lectures. The overall mean score achieved on the eleven scenarios was 50.4% for
anesthesiology, 47.0% for internal medicine, 55.7% for cardiology, and 42.3% for
surgery. CONCLUSIONS: Although the majority of residents were aware of the 2007
ACC/AHA guidelines, fewer received lectures and regardless of specialty,
implementation of these guidelines was poor. There exists significant room for
improvement in the understanding of preoperative assessment of non-cardiac
surgery patients.
PMID- 26442391
TI - PSEUDOCHOLINESTERASE DEFICIENCY IN A OCTOGENARIAN UNDERGOING TOTAL INTRAVENOUS
ANESTHESIA; IMPLICATIONS FOR NEUROMONITORING.
AB - Pseudocholinesterase deficiency manifests as prolonged motor blockade after the
administration of succinylcholine. A previously unknown homozygous form of the
disease, became apparent during a lumbar laminectomy seriously limiting the
ability to monitor motor evoked potentials and perform electromyelography (EMG).
Moreover, concerns were raised as to how the enzyme deficiency would affect the
metabolism of remifentanil and other esters during a total intravenous
anesthetic. We present the perioperative management of the patient and a
literature review of the syndrome. The patient provided written permission for
the authors to publish this report. At our institution, IRB review and approval
is not required for a single case report.
PMID- 26442392
TI - AN AUDIT OF THE CURRENT PRACTICES OF AIRWAY MANAGEMENT IN PATIENTS UNDERGOING
SURGERY FOR ATLANTO-AXIAL DISLOCATION IN A SINGLE INSTITUTION.
AB - BACKGROUND: Patients with atlanto axial dislocation (AAD) undergo stabilisation
procedures under general anesthesia. Airway management in these patients is
difficult as cervical spine movements during laryngoscopy can worsen spinal cord
damage. Though multiple airway devices are used to intubate the trachea of these
patients, there is no evidence of superiority of one technique over another. This
retrospective study was designed to audit the practice of airway management
during surgery for AAD over a 5 year period, starting from 2006 till 2011.
METHODS: Patients' demographics, airway intervention techniques, types of
surgical procedures, postoperative neurological and respiratory deterioration
were recorded from the case files. Association between the types of airway
interventions and the postoperative neurological and respiratory deterioration
were analysed. RESULTS: One hundred and six patients underwent surgery for AAD
during the study period. Sixty one percent of the patients were intubated with
the help of a fiberoptic bronchoscope (FOB) and among them 15% received general
anesthesia to facilitate FOB. Eighteen patients developed neurological
deterioration and 15 patients developed respiratory weakness requiring
ventilation postoperatively. Congenital AAD patients had higher chances for
extubation at the end of surgery when intubated using FOB (p = 0.007). Among the
AAD patients, female gender had significantly higher incidence of neurological
deterioration compared to males. CONCLUSION: In the current audit, there was no
correlation between the perioperative variables and postoperative respiratory and
neurological deterioration. Most of the respiratory problems occurred between 2-5
postoperative days stressing the need for extended intensive postoperative
monitoring of these patients.
PMID- 26442393
TI - ULTRASOUND-GUIDED SCIATIC POLITEAL NERVE BLOCK: A COMPARISON OF SEPARATE TIBIAL
AND COMMON PERONEAL NERVE INJECTIONS VERSUS INJECTING PROXIMAL TO THE
BIFURCATION.
AB - OBJECTIVE: Block of the sciatic nerve at the popliteal fossa can be performed
using the ultrasound machine; it may be proximally or distally to the bifurcation
of the sciatic nerve using lateral, medial, or posterior approaches. It is
frequently used for surgeries below the knee specially the foot and ankle
operations. PURPOSE: This study compares one and two injections of the sciatic
nerve in the popliteal fossa with ultrasound-guided block in foot or ankle
surgeries. METHODS: Forty patients received ultrasound-guided sciatic nerve block
with the nerve stimulator, using the posterior approach. The patients were
enrolled into two groups (20 patients each), group 1: received one injection at 2
cm cephalad to the bifurcation of the sciatic nerve, and group 2: received two
injections caudate to the sciatic bifurcation; one for tibial nerve and the other
for common peroneal nerve. All patients received 20 ml of levobupivacaine 0.5%.
The block performance time, block efficacy, success rate, complications and
patient's satisfaction were evaluated. RESULTS: Block the tibial and common
peroneal nerves separately (two injections) distal to the point of bifurcation of
the sciatic nerve has a significantly (P < 0.05) faster time to complete sensory
block of tibial and common peroneal nerves compared to a pre-bifurcation sciatic
nerve block (one injection). The complete motor block, block time performance,
success rate and patient's satisfaction were not significantly different between
groups (P > 0.05). CONCLUSION: The block of tibial and common peroneal nerves
separately distal to the sciatic nerve bifurcation is superior to single
injection block of sciatic nerve above the bifurcation in the popliteal fossa as
regard complete sensory block time.
PMID- 26442394
TI - INTRAVENOUS DEXAMETHASONE IN COMBINATION WITH CAUDAL BLOCK PROLONGS POSTOPERATIVE
ANALGESIA IN PEDIATRIC DAYCARE SURGERY.
AB - BACKGROUND: This study was conducted to determine if intravenous dexamethasone
combined with caudal block was able to prolong post-operative analgesia in
pediatric daycare surgeries. METHODS: Sixty four ASA I or II children aged 3 to
10 year old scheduled for daycare open unilateral herniotomy received general
anesthesia and caudal block using 0.25% levobupivacaine 0.75 mg.kg(-1) with
suppository paracetamol 30 mg.kg(-1). After anesthesia induction, they were
randomized to receive either intravenous dexamethasone 0.5 mg.kg(-1) (Group I) or
same volume intravenous normal saline (Group II). Postoperatively, pain scores
were assessed using Wong- Baker faces scale. At home, their parents assessed and
recorded the pain scores, time to first oral paracetamol served and frequency of
paracetamol given in two consecutive days post surgery. On the third
postoperative day, these information were gathered from the parents via a phone
call. RESULTS: There were statistically significant differences between Group I
and Group II in the median time to first paracetamol (800 vs 520 min, p = 0.01),
mean pain scores postoperative day 1 (1.9 +/- 2.0 vs 3.5 +/- 2.2, p = 0.05), mean
pain score-postoperative day 2 (0.8 +/- 1.6 vs 2.3 +/- 2.0, p = 0.03) and mean
frequencies of paracetamol given on postoperative day 2 (0.3 +/- 0.8 vs 1.1 +/-
1.0, p = 0.02). CONCLUSION: A single intravenous dexamethasone dose when combined
with caudal block reduces postoperative pain, decreases paracetamol requirement
and prolongs analgesic duration in children after open herniotomy.
PMID- 26442395
TI - COMPARATIVE STUDY BETWEEN ULTRASOUND AND NERVE STIMULATOR GUIDED SCIATIC NERVE
BLOCK THROUGH THE ANTERIOR APPROACH.
AB - INTRODUCTION: The aim of the current study was to compare block of the sciatic
nerve through the anterior approach by two methods, namely, the nerve-stimulator
guided and ultrasound-guided, with or without nerve stimulation, with regard to
the ease of performance, reliability and safety of this approach. PATIENTS AND
METHODS: 36 adult patients were randomly allocated equally into one of 2 main
groups: "Nerve Stimulator-Guided Group (NSG)" where the nerve was located by
nerve stimulator only and "Ultrasound guided group (USG)" where the sciatic
nerves were blocked by a stimulated needle under guidance of the ultrasound.
Assessment of performing each technique, sensory and motor blockades, occurrence
of acute systemic toxicity and haematoma formation were compared. RESULTS: Only
one-third of the sciatic nerves could be visualized by US. This did not affect
the block execution time but caused less number of needle passes in a
statistically significant value. Sensory and motor block showed significant
differences between the 2 groups. Criteria of acute systemic toxicity and
occurrence of hematoma were not reported in both groups. CONCLUSION: Results of
the current study showed that the addition of ultrasound to nerve stimulator in
the anterior approach to the sciatic nerve block added only little to the ease of
performance, reliability and safety. This was because only one-third of the
nerves could be seen. More practice, better machines and new blocking techniques
may be needed to overcome the problem of anisotropy of the nerve.
PMID- 26442396
TI - WOUND INSTILLATION OF LOCAL ANESTHETIC BUPIVACAINE FOR POSTOPERATIVE ANALGESIA
FOLLOWING LUMBAR LAMINECTOMY.
AB - PURPOSE: Lumbar laminectomy is a commonly performed procedure in neurosurgical
and orthopedic practice. Postoperative pain reliefhelps in early mobilization,
initiation of physiotherapy, provides satisfaction to the patients and plays an
important role in reducing the morbidity and mortality. This prospective study
investigated the simple technique of instillation of wound with bupivacaine and
leaving a contact time of 60 seconds on postoperative pain following lumbar
laminectomy. METHODS: 32 ASA I and II patients scheduled for laminectomy were
randomly allocated to receive either 20 ml of normal saline (group I) or 0.25% of
bupivacaine (group II) into the wound after securing hemostasis. After a dwell
time of 60sec the wound was closed in layers without mopping or suctioning. After
extubation, the pain scores were evaluated by visual analog scale at every 4 hrs.
for 24hrs and also the time for first demand of analgesia, number of analgesic
demands and the total amount of analgesia consumed were noted by an independent
observer.. RESULTS: The median duration of analgesia in group I was 8.8 [5-11]
and in group II 13 [8.5-16] hrs. with a p = 0.04. The number of demands and the
amount of analgesia consumed was also statistically significant. CONCLUSION:
Wound instillation technique is simple, safe and effective in management of acute
pain management after lumbar laminectomy and can be used as one among the
multimodal armamentarium in pain management.
PMID- 26442397
TI - THE EFFECTS OF INTRATHECAL NEOSTIGMINE ADDED TO BUPIVACAINE ON POSTOPERATIVE
ANALGESIC REQUIREMENT IN PATIENTS UNDERGOING LOWER LIMB ORTHOPEDIC SURGERY.
AB - BACKGROUND: Several additives have been suggested to enhance analgesic effect of
local anesthetic agents to decrease the adverse effects of them and increase the
degree of satisfaction. We designed this randomized double-blind controlled study
to evaluate the analgesic efficacy of the neostigmine added to bupivacaine using
spinal anesthesia in patients undergoing lower limb orthopedic surgery. METHODS:
Sixty patients 18-80 yr old American Society of Anesthesiologists (ASA) physical
status I or II, scheduled for femur surgery under spinal anesthesia, were
recruited in a prospective, double-blinded, randomized way. The patients were
randomly allocated to one of two groups of 30 each. The neostigmine group (group
N) received bupivacaine 20 mg combined with 25 ug neostigmine, and the placebo
group (group C) received bupivacaine 20 mg combined with 0.5ml distilled water
(intrathecally) 5 minutes prior to surgery. The time to the first analgesic
request, analgesic requirement in the first 12 hours after surgery, the duration
of sensory and motor blockade, the incidence of adverse effects such as
nausea,vomiting,hypotension, ephedrine requirements, bradycardia, and hypoxemia
were recorded. RESULTS: Patients receiving neostigmine had a significantly
prolonged duration of motor block (C95% CI 30.27 to 87.65; P < 0.001) and sensory
block (C95% CI 101.04 to 224.64; P < 0.001) compared to the control group. The
difference of the mean time to the first analgesic request was also significantly
longer in neostigmine group (C95% CI 83.139 to 208.526; P < 0.001). The total
analgesic consumption during the first 12 hours after surgery was devoid of any
significant difference between groups N and C (p = 0.41).The two groups were not
significantly different in terms of intraoperative and postoperative side
effects. CONCLUSION: Intrathecal neostigmine 25 ug with bupivacaine caused a
prolonged time to the first analgesic request and its use was not associated with
any side effects.
PMID- 26442398
TI - THE BENEFICIAL VALUES OF TRANSOESOPHAGEAL DOPPLER IN INTRAOPERATIVE FLUID
GUIDANCE VERSUS STANDARD CLINICAL MONITORING PARAMETERS IN INFANTS UNDERGOING
KASAI OPERATION.
AB - BACKGROUND: Fluid overload in infants can result from inappropriate volume
expansion (VE). The aim of this work was to evaluate the beneficial values of
Transoesophageal Doppler TED in intraoperative fluid guidance versus standard
clinical monitoring parameters in infants undergoing Kasai operation. METHODS:
Forty infants scheduled for Kasai procedure were randomly allocated into two
groups (Doppler and clinical group). In Doppler group decided to provide VE (10
30 m1/kg of Hydroxyethyl starches HES) when the index stroke volume decreased by
>= 15% from the baseline value, in clinical group, hemodynamic variables
triggering colloid administration mean arterial blood pressure (MAP) less than
20% below baseline or central venous pressure (CVP) < 5 cmH2O in both groups:
Ringer's acetate was infused at constant rate (6 m 1/kg/h). Standard and TED
derived data were recorded before and after VE. Follow up the postoperative
outcome and hospital stay. RESULTS: There were significantly lower mean volume of
HES (42.85 +/- 3.93 versus 84 +/- 14.29 ml) and percent of infants required it
(30% versus 90%) associated with earlier tolerance to oral feeding (2 +/- 0.66
versus 3.4 +/- 0.51), shorter hospital stay (5.30 +/- 0.47 versus 6.7 +/-
[symbols: see text] days) and lower rate of chest infection (15% versus 30%) in
Doppler group than clinical group. There was no difference between the two
studied groups regarding heart rate, MAP. CONCLUSIONS: TED guided intraoperative
fluid intake in infants undergoing Kasai operation optimize fluid consumption and
improve outcome associated with shorter hospital stay.
PMID- 26442399
TI - DESFLURANE COMPARED TO SEVOFLURANE FOR CIRRHOTIC PATIENTS UNDERGOING MAJOR LIVER
RESECTION. A RANDOMIZED CONTROL STUDY.
AB - BACKGROUND: Major liver resection is associated with haemodynamic, hepatic and
renal changes as a result of the procedure. AIM: To compare Desflurane (D) versus
Sevoflurane (S) on hepatic, renal functions, haemodynamics and perioperative
course for cirrhotic patients undergoing major liver resection. PATIENTS AND
METHODS: A prospective randomized control study with 50 patients (Child A) (D, n
= 25 and S, n = 25). End tidal D or S adjusted with Entropy (40-60).
Haemodynamics monitored with invasive blood pressure and trans-oesophageal
Doppler (TED). Liver and kidney function tests, blood Glutathione-S-transferase
(GST), urinary microalbuminuria (Microalb) were assayed. Extubation time and
anaesthetic consumption were recorded. RESULTS: Systemic vascular resistance
(SVR) post-resection and stroke volume of D vs S were 835.04 +/- 12.02 vs 778.16
+/- 11.97 dyn.sec.cm(-5), P < 0.01, and 85.72 +/- 2.95 vs 76.16 +/- 6.52 ml, P <
0.01 respectively. Doppler corrected flow time (FTc) between groups were
comparable (P > 0.05). No difference post-operatively regarding hepatic and renal
functions, and urine Microalb (14.76 +/- 3.95 vs l4.24 +/- 8.65 ug/ml, P = 0.78),
but a statistically difference was found with GST (0.046 +/- [symbols: see text],
vs 0.043 +/- [symbols: see text] IU/ml, P < 0.01). Despite a higher D consumption
(73 +/- 17 vs 64 +/- 22 ml, P = 0.102), cost in Egyptian pounds (LE) was lower
with D (141.14 +/- 32.90 vs 320.60 +/- 114.01, LE, P < 0.01). Extubation time and
ICU stay with D vS (4.52 +/- 2 vs 7.72 +/- 2 min, P < 0.01) and (1.40 0.50 vs
1.64 +/- 0.48, days P = 0.09) respectively. CONCLUSION: Neither D nor S were
clinically superior to the other with respect to liver and kidneys functions, but
D was found to preserve better the haemodynamic parameters and enhance recovery
at a lower cost.
PMID- 26442400
TI - MYOCARDIAL OXYGENATION DURING ACUTE NORMOVOLEMIC HEMODILUTION: IMPACT OF
HYPOCAPNIC ALKALOSIS.
AB - BACKGROUND: Increases in myocardial blood flow preserve myocardial oxygenation
during moderate acute normovolemic hemodilution. Hypocapnic alkalosis (HA) is
known to cause coronary vasoconstriction and increase hemoglobin-oxygen affinity.
We evaluated whether these effects would compromise myocardial oxygenation during
hemodilution. METHODS: Eighteen anesthetized dogs were studied. Myocardial blood
flow (MBF) was measured with radioactive microspheres. Arterial and coronary
sinus samples were analyzed for oxygen content and plasma lactate. Myocardial
oxygen supply, oxygen uptake, and lactate uptake were calculated. HA (PaCO2, 23
+/- 2 (SD); pHa, 7.56 +/- 0.03) was induced by removal of dead space tubing at
baseline (n = 8) and during hemodilution (n = 10), with hematocrit at 43 +/- 4%
and 19 +/- 2%, respectively. RESULTS: Hemodilution during normocapnia caused
decreases in arterial oxygen content (19.9 +/- 2.4 to 9.3 +/- 1.2 ml/100; P <
0.05) and the coronary arteriovenous 02 difference (13.0 +/- 3.0 to 6.4 +/- 0.9
ml/100ml; P < 0.05). MBF increased (52 +/- 12 to 111 +/- 36 ml/min/100g; P <
0.05) to maintain myocardial oxygen supply and oxygen uptake. Myocardial lactate
uptake increased (31 +/- 19 to 68 +/- 35 ueq/min/100g; P < 0.05). At normal
hematocrit, HA decreased MBF (57 +/- 18 to 45 +/- 10 ml/min/100; P < 0.05),
implying vasoconstriction, accompanied by decreased myocardial oxygen supply.
These myocardial effects of HA were not apparent during hemodilution. HA did not
alter myocardial lactate uptake during hemodilution. CONCLUSION: When HA was
induced during hemodilution, its ability to cause coronary vasoconstriction was
lost, and myocardial oxygenation remained well preserved.
PMID- 26442401
TI - ASSESSMENT OF PREOPERATIVE AND POSTOPERATIVE ANXIETY AMONG ELECTIVE MAJOR SURGERY
PATIENTS IN A TERTIARY HOSPITAL IN NIGERIA.
AB - BACKGROUND: Anxiety is an unpleasant emotional experience that involves feelings
of tension, apprehension, nervousness and high autonomic activity. Few studies
have been conducted in Nigeria on anxiety levels among patient undergoing
surgical operation. The aim of this study is to assess preoperative and
postoperative anxiety level of patients and identify factors that may influence
patient's preoperative anxiety level. METHODS: Fifty one adult patients scheduled
for elective surgery in a tertiary public hospital in Nigeria were assessed a day
before and after their surgery using a questionnaire with socio-demographic and
clinical details. Anxiety was assessed with the state portion of the State-Trait
Anxiety Inventory (STAI) and different factors responsible for their anxiety were
selected from a list. Statistical analysis was done using SPSS version 17.
RESULT: Twenty-six patients (51.0%) had significant preoperative anxiety while 8
(15.7%) had significant postoperative anxiety. The patients preoperative mean
anxiety score of STAI (42.72 +/- 9.84) was statistically significantly higher
than their postoperative mean anxiety score (37.73 +/- 8.44; p = .001). In 10
items of STAI, there were significant differences between the preoperative and
postoperative mean STAI scores. Fear of complications and result of operation
were the most common factors responsible for preoperative anxiety while few
patients were anxious about nil per mouth, getting stuck with needle and harm
from doctor/nurse mistake. CONCLUSION: The prevalence of preoperative anxiety is
high in Nigerian surgical patients. Psychological preparation and provision of
correct information that addresses identified factors may help in reducing
preoperative anxiety.
PMID- 26442402
TI - THE EFFECTS OF LISTENING TO THE MOTHER'S HEARTBEAT ON THE DEPTH OF ANAESTHESIA IN
CHILDREN.
AB - BACKGROUND: The present study aimed to evaluate the effects of listening to the
mother's heartbeat and womb sounds on the depth of anaesthesia in children.
METHODS: The present study included 40 children scheduled for minor surgery under
general anaesthesia, with an American Society of Anaesthesiologists (ASA) status
of 1 to 2. Anaesthesia was induced with sevoflurane, and maintained with
sevoflurane and oxygen in nitrous oxide. Patients were randomly divided into two
groups. The children in Group I were made to listen to recordings of their
mothers' heartbeat and womb sounds via earphones during anaesthesia induction,
while those in Group II were made to listen to ambient noise via earphones. The
music was turned off when the inhalational anaesthetics were discontinued.
Intraoperative monitoring included electrocardiogram (ECG) recordings, heart rate
(HR), oxygen saturation, non-invasive systolic blood pressure (SBP) and diastolic
blood pressure (DBP), bispectral index system (BIS), end-tidal (ET) sevoflurane,
ET N2O, ET CO2, and SaO2. RESULTS: In Group I, there was a significant decrease
in bispectral index (BIS) values over time (p < 0.05). Although blood pressure
and heart rate were lower in Group I, no significant differences between the
groups were detected. While the duration of extubation was shorter in Group I,
overall, there was no significant difference between the groups. CONCLUSION: We
found that children exposed to recordings of their mothers' heartbeat and womb
sounds in addition to music had lower BIS values under anaesthesia, which
indicates deeper anaesthesia levels.
PMID- 26442403
TI - LEARNING BY SIMULATION.
AB - The future appears bright for the use of simulation in medical education.
Medical, nursing, and allied healthcare students trained through simulation have
opportunities to practice hands on techniques, teamwork, and communication
through trial and error in a safe environment before working with live patients.
The cost of high-fidelity simulation will continue to make its use prohibitive
and challenging for some programs though the use of low-fidelity simulation,
standardized patients, and role-playing continues to have measureable qualitative
value. Cost center sharing is one way for programs on a tight budget who desire
high-fidelity simulation to access this valuable skills-building, outcome
improving medical education adjunct tool.
PMID- 26442404
TI - ULTRASOUND GUIDED DORSAL RAMUS NERVE BLOCK FOR REDUCTION OF POSTOPERATIVE PAIN IN
PATIENTS UNDERGOING LUMBAR SPINE SURGERY: A CASE SERIES IMAGING STUDY.
AB - In patients undergoing spine surgery postoperative pain management can often be
complicated with side effects associated with high dose narcotic such as
respiratory depression and those associated with non-steroidal anti-inflammatory
drugs such as interference with bone healing process. Local anesthetics can help
in both decreasing postoperative pain and minimizing side effects associated with
systematically administered analgesics. This report describes the use of
preoperative ultrasound guided dorsal ramus nerve block to reduce postoperative
pain in six patients undergoing lumbar spine surgery under general anesthesia.
PMID- 26442405
TI - A SHARED OPERATIVE FIELD AND THE DISPUTE--IS THERE A WAY OUT?
AB - Submental intubation is an alternative to tracheostomy in patients requiring
surgical access to both oral and nasal cavities. It is relatively safe, simple,
and low morbidity procedure and requires only basic surgical equipment to
perform. We successfully performed a submental intubation in a young patient with
maxillofacial hypoplasia undergoing Le Fort I maxillary advancement without any
intra- and post-operative complications.
PMID- 26442406
TI - RESIDUAL NEUROMUSCULAR BLOCKADE (RNMB): ROCURONIUM'S DEFASCICULATING DOSE,
NEOSTIGMINE- INDUCED WEAKNESS, AND AWARENESS DURING RECOVERY.
PMID- 26442407
TI - [Can We Avoid the War?].
PMID- 26442408
TI - [Measurement of the Minimum Pressure in the Bronchial Cuff during One-lung
Ventilation Using a Capnometer].
AB - BACKGROUND: It is recommended to avoid overinflation of the bronchial cuff,
leading to ischemic pressure damages to the respiratory mucosa and bronchial
rupture. We investigated the minimum bronchial cuff pressure of 35 Fr double
lumen tubes (DLTs) during one lung ventilation using a capnometer. METHODS: We
studied 50 patients who were scheduled to undergo thoracic surgery. General
anesthesia was induced and the patients were intubated with 35 Fr left DLT. With
a fiberoptic bronchoscope, the DLT was positioned appropriately. The bronchial
cuff was inflated first with air 3-3.5 ml. Lung isolation was confirmed by
auscultation. Measurements were performed with the patient in the lateral
position. Ventilating one lung isolatedly for 5 minutes, we confirmed non
ventilated condition with a capnometer displaying flat line. The bronchial cuff
was deflated 0.5-ml steps just before displaying the respiratory pattern by the
capnogram. The bronchial cuff pressure and volume were recorded at this point
RESULTS: The minimum pressures of bronchial cuff (volume) for one lung
ventilation are for male 5.46 +/- 0.6 cmH2O (2.33?0.1 ml) and for female 1.5?0.5
cmH20 (1.09 +/- 0.3 ml). These values are smaller than the recommended value (<
25 cmH2O). There was no case in which the collapse of the operated lung was
insufficient. CONCLUSIONS: In this study, the bronchial pressure higher than 12
cmH2O was not necessary for one lung ventilation. If high intracuff pressure is
necessary to seal the bronchus, there are possibilities of the incompatibility of
the size of DLT and the herniation of the bronchial cuff to the proximal side.
The method of confirmation of OLV using a capnometer can display the non
ventilated condition on the monitor objectively. We can thus decrease troubles
during operations.
PMID- 26442409
TI - [Side Effects of Continuous Fentanyl Infusion for Postoperative Pain Relief in
Children].
AB - BACKGROUND: There have been many reports on the use of morphine for postoperative
pain relief in children, but the use of fentanyl for this purpose has not
frequently been described. We clarified the details of side effects exhibited in
children who had received continuous fentanyl infusion for postoperative pain
relief METHODS: The subjects are 1,166 children aged between 0 and 14 years who
underwent continuous fentanyl infusion for postoperative pain relief within the
previous 4 years. Fentanyl was administered at a dose of 0.5 or 1.0 MUg x kg(-1)
x hr(-1), and with continuous use of pulse oximeter, the pulse rate, SpO2,
respiratory rate, BP, sedation score, and presence/absence of nausea/vomiting
were recorded every 2 hours. The frequencies of side effects were retrospectively
examined. RESULTS: Severe side effects, including respiratory depression, for
which mask ventilation or tracheal intubation was required were observed in 0.77%
of cases. No subjects died or developed permanent sequelae. Nausea/vomiting
occurred in 25.4% of cases. CONCLUSIONS: Using monitoring systems that facilitate
the early detection of and intervention in respiratory depression, we can safely
administer continuous fentanyl infusion for postoperative pain relief in
children. It is necessary to adopt countermeasures against nausea/vomiting.
PMID- 26442410
TI - [Examination of the Untoward Removal of the Epidural Catheter Due to Differences
in Its Fixation Methods].
AB - BACKGROUND: Epidural anesthesia is a useful tool for postoperative pain control.
However, inappropriate fixing of the catheter not only hinders the analgesic
effect, but could lead to serious accidents as a result of the untoward removal
of the epidural catheter. METHODS: In our hospital, in order to reduce the
removal of catheter, we introduced a new method of fixing by Steri-StripTM from
fiscal 2011. RESULTS: We compared 2337 cases of epidural use for general
anesthesia in one fiscal year of 2010. In fiscal year 2011, 2500 examples were
examined backward. CONCLUSIONS: The group using the Steri-Strip, was able to
significantly reduce the untoward removal (P = 0.002).
PMID- 26442411
TI - [A Case of Brainstem Cavernous Hemangioma Showing False Positive Response to
Electromyographic Tracheal Tube].
AB - Brainstem cavernous hemangioma is a complex lesion associated with hemorrhage and
neurological deficit. The damage of the vagus nerve is a devastating surgical
complication. Therefore, intraoperative anatomical and functional evaluation of
this nerve is crucial. We used electromyographic tracheal tube (EMG tube)to
monitor electromyogram from the vocal cord. We report a case of brainstem
cavernous hemangioma showing false positive response to EMG tube. A 66-year-old
woman underwent resection of cavernous hemangioma in the pontine tegmentum.
General anesthesia was induced with remifentanl, propofol, and suxamethonium, and
was maintained with oxygen, air, remifentanil and propofol. We monitored
somatosensory evoked potentials, motor evoked potentials, and electromyogram of
the vocal cord, orbicularis oculi, orbicularis oris and lateral rectus. When the
manipulation reached brainstem, slight spontaneous respiration (SR) appeared on
capnogram. Simultaneously, an alarm rang. Exposed nerves were stimulated
electrically. However, there was no electromyographic response on the vocal cord.
We concluded that the cause was SR accompanied by vocal cord movement.
Remifentanil was increased up to 1 MUg x kg(-1) x min(-1). SR did not disappear.
Remifentanil was not increased any more without hindering the operation. Her
operative course was uneventful. It is necessary to pay attention to false
positive response caused by SR with EMG tube.
PMID- 26442412
TI - [Airway Obstruction Caused by Heat and Moisture Exchange Filter Used during
General Anesthesia: A Case Report and an In Vitro Study].
AB - BACKGROUND: A previously healthy 54-year-old woman underwent a resection of the
acoustic tumor. Following induction of general anesthesia and tracheal
intubation, volume-controlled ventilation was started and the patient was placed
in the left park bench position. The heat and moisture exchange filter (HMEF) was
placed within the ventilatory circuit and positioned below the patient's head to
avoid unintentional extubation. Six hours after the start of surgery, peak
inspiratory pressure gradually rose, and 2 hours later ventilation of the
patient's lung became increasingly difficult. When the HMEF was replaced, normal
breathing was promptly restored. METHODS: We reproduced this scenario with a
similar HMEF under the same ventilator settings by adding 0-8 g of normal saline
into the HMEF housing, and measured the inspiratory pressure and tidal volume
across the HMEF. RESULTS: When instilling 4 g of saline, an increase in
inspiratory pressure occurred. CONCLUSIONS: This case shows a potential risk of
unexpectedly early occurrence of obstruction of the HMEF due to accumulation of
condensed water within the device when the HMEF was positioned below the
patient's head. We recommend selection of the appropriate HMEF and suitable
mounting to avoid this problem.
PMID- 26442413
TI - [Intubation Using a Double-lumen Tube with a Combination of Fiberoptic
Bronchoscope and the Glidescope in a Patient with Difficult Airway].
AB - A 54-year-old man with lung cancer was scheduled for thoracoscopic upper lobe
resection under general anesthesia. About half a year previously, he had
undergone surgery for oropharyngeal cancer and tongue cancer. As a result of the
surgery, elasticity of the neck skin bending of the neck were restricted
(Mallampati classification IV). A narrow-bored tracheostomy tube (speech cannula)
was inserted. In the operating room, the tip of a 5.0 mm ID standard tube was
inserted from the tracheostomy tube, and connected to a breathing circuit.
Anesthesia was induced with inhalation of sevoflurane, followed by intravenous
propofol, fentanyl, and rocuronium. Four anesthesiologists were required to
intubate the trachea. One person held the tracheal tube placed in the tracheotomy
tube. The second person performed jaw thrusting. The third person inserted the
Glidescope to shift the transplanted tongue to the side. It was then possible for
the forth anesthesiologist to manage to see the glottis using a fiberoptic
bronchoscope, and a double-lumen tube (DLT) could be inserted to the trachea
orally. Inserting a DLT over the fiberoptic bronchoscope is a blind method, but
we felt that combined with a variety of tools such as video laryngoscope, the
success rate in intubation will increase.
PMID- 26442414
TI - [A Case of Septic Shock Immediately following Cesarean Section].
AB - Here we report a case of severe septic shock immediately following cesarean
section. A pregnant woman with dichorionic diamniotic twins was diagnosed with
preterm rupture of membranes (PROM). Ritodrine hydrochloride and betamethasone
did not sufficiently relieve abdominal extension; emergency cesarean section was
scheduled 4 days later, at 31 week 5 day gestation. The patient did not show any
symptoms or laboratory data suggesting infection. Spinal anesthesia was initiated
with 2.2 ml of 0.5% bupivacaine hydrochloride and fentanyl 10 MUg at L3-4;
sensory loss (T3) was confirmed. Epidural anesthesia at L1-2 was performed for
postoperative pain control. Surgery proceeded uneventfully, but the first baby
did not respond to neonatal CPR. One hour after surgery, the patient showed signs
of shock and a fever of 40.9 degrees C. Catecholamine and antibiotics relieved
her symptoms. Retrograde infection of Escherichia coli was attributed to fetal
distress and septic shock. Early phase septic shock should be considered in
pregnant women with PROM.
PMID- 26442415
TI - [Anesthetic Induction in a Patient with Giant Ovarian Tumor Who Developed Severe
Hemodynamic Instability].
AB - A 45 year-old woman underwent a laparotomy for a giant ovarian tumor under
general anesthesia. Preoperative CT scan revealed a 30 cm-diameter tumor
compressing IVC. She had slight respiratory discomfort on supine position, but
respiratory function test showed no abnormalities. In the operating room, after
oxygenation for 3 minutes, general anesthesia was induced with fentanyl 100 MUg,
propofol 90 mg and rocuronium 40 mg on supine position. Immediately after the
induction, her systolic blood pressure and heart rate fell to 45 mmHg and 40
beats per minute, respectively. We considered that her hemodynamic instability
was supine hypotensive syndrome due to giant ovarian tumor. Therefore we placed
her 30 degree right side up and pushed her tumor to the left so as not to
compress the IVC. We rapidly injected acetated Ringer's solution 500 ml,
ephedrine 12 mg and phenylephrine 0.1 mg, and her hemodynamic status soon
recovered to normal ranges. The anesthetic induction of a patient with a giant
ovarian tumor is challenging. Some reports recommend strategies such as induction
on lateral position or suctioning tumor contents before induction. Careful
induction of general anesthesia is required for these patients.
PMID- 26442416
TI - [Development of Takotsubo Cardiomyopathy during Recovery from General Anesthesia:
A Case Report].
AB - Takotsubo cardiomyopathy is a cardiac syndrome characterized by transient left
ventricular dysfunction. A 61-year-old woman underwent laparoscopic
cholecystectomy under general anesthesia. During recovery from general
anesthesia, several arrhythmias occurred without cardiac collapse following
desflurane discontinuation and sugammadex sodium administration. She had a chest
pain after extubation, with ST segment elevation in leads aV(L) and V2-4.
Emergency left ventricular angiogram revealed no significant coronary stenosis,
and excessive contraction of the base and severe hypokinesis of the apex
suggested Takotsubo cardiomyopathy. Sympathetic hyperactivity during acute
recovery from anesthesia with desflurane discontinuation and muscle relaxant
reversal with sugammadex sodium was considered the likely cause of Takotsubo
cardiomyopathy.
PMID- 26442417
TI - [Airway Management Utilizing an air-Q blocker in a Patient with Motor Neuron
Disease and Soft Palate Paralysis].
AB - A 67-year-old woman suffering from hoarseness or dysphagia was diagnosed with
motor neuron disease. She was scheduled for laparoscopic cholecystectomy under
general anesthesia for suspected gallbladder cancer. She was concerned about the
exacerbation of her hoarseness or dysphagia from tracheal intubation. We
therefore decided to perform airway management by using supraglottic device air-Q
blocker, through which a gastric tube could be inserted. We first passed the
gastric tube through the outer blocker hole and inserted it into the esophagus
using Magill forceps. The air-Q blocker was placed position under the guidance of
a McGrath videolaryngoscope. Sealing pressure was over 20 cmH2O and mechanical
ventilation was performed uneventfully during artificial pneumoperitoneum. We
were able to deflate the stomach and perform tracheal suction via the inner hole
of the air-Q. Following the operation, the patient developed neither hoarseness
nor pharyngeal pain.
PMID- 26442418
TI - [Acute Ventilatory Failure during Prone Thoracoscopic Esophagectomy with Carbon
Dioxide Insufflation in a Patient Managed by a Single Lumen Tracheal Tube].
AB - A 67-year-old woman underwent prone thoracoscopic esophagectomy with carbon
dioxide (CO2) insufflation. After insertion of an epidural catheter, general
anesthesia was induced with propofol, sevoflurane, remifentanil and rocuronium.
The trachea was intubated with a single lumen endotracheal tube (SLET). CO2
insufflation at 5 mmHg with the SLET deflated the right lung and provided
excellent visualization without respiratory instability. The left side pleura was
injured during the inferior mediastinal lymphadenectomy and the patient went into
sudden profound hypoventilation with an increase in end-tidal CO2 from 43 to 64
mmHg. We observed the trachea with bronchofiberscope and the SLET was correctly
located and not obstructed. We were convinced that bilateral pneumothorax
occurred because the left side pleura was injured and auscultation revealed
decreased breath sounds over the left hemithorax. We asked the surgeon to
discontinue the insufflated CO2 and both lungs were fully expanded. The operation
was then carried out successfully without further untoward event. The patient was
successfully extubated at the intensive care unit on postoperative day 1. The CO2
insufflation during thoracoscopic esophagectomy can cause bilateral pneumothorax
and we recommend to inflate the bilateral lungs regularly for the continuation of
the surgery.
PMID- 26442419
TI - [General Anesthesia for a Patient with Purulent Spondylitis with Retropharyngeal
Abscess and Vocal Cord Dysfunction: A Case Report].
AB - A 43-year-old man was admitted to our hospital for neck pain, and diagnosis was
fixed as purulent spondylitis with retropharyngeal abscess and vocal cord
dysfunction. Deteriorating paresthesia, paralysis and airway narrowing needed
airway management emergency cervical laminoplasty and abscess drainage under
general anesthesia. On standby of an otorhinolaryngologist for urgent
tracheotomy, nasal tracheal intubation with bronchofiberscope was performed in
the patient with semi-awake condition. Postoperative airway narrowing and vocal
cord dysfunction improved, and the trachea was extubated on the third day after
surgery.
PMID- 26442420
TI - [Change in Perioperative Hemostatic Function in Patients Undergoing Hepatic
Resection for Primary and Metastatic Liver Cancer].
AB - BACKGROUND: Patients undergoing primary hepatic resection often develop
hemostatic dysfunction associated with cirrhosis. METHODS: We retrospectively
surveyed pre- and postoperative prothrombin time (PT) and the PT expressed as
international normalized ratio (PT-INR) in 39 patients undergoing primary liver
resection. We also compared PT changes between primary and metastatic cancer
cases (8 cases). RESULTS: Postoperative PT-INR was 1.40 +/- 0.38, which was
significantly prolonged compared to preoperative PT-INR of 1.08 +/- 0.07.
Preoperative PT was over 70% in all 39 patients undergoing primary liver
resection, whereas postoperative PT was less than 60% in 13 of 39 patients. No
significant difference was found in preoperative PT-INR between primary and
metastatic cancer cases, but postoperative PT-INR was significantly prolonged in
primary cancer cases. CONCLUSIONS: Patients undergoing primary liver resection
are susceptible to hemostatic dysfunction, even with preoperative PT levels
within normal limits.
PMID- 26442421
TI - [Perioperative Management of a Patient with Severe Parkinson's Disease with
Intravenous Levodopa Administration].
AB - A 70-year-old man with severe Parkinson's disease was scheduled for thoracic
aortic aneurysm resection and aortic valve replacement. We administered levodopa
intravenously during the perioperative period to avoid the malignant syndrome
which is reported to arise with abrupt cessation of anti-Parkinson's drugs. The
dose of intravenous administration was tapered with the resumption of oral
intake. No manifestation of malignant syndrome was observed. We measured blood
concentrations of levodopa several times during the perioperative period. The
concentration of levodopa during the surgery was relatively high; however no
adverse events of overdose (e.g. dyskinesis) occurred. In the postoperative
period, administration of levodopa was changed to the oral route and serum levels
of levodopa showed a notable decrease, the cause of which may be poor absorption
through the digestive system during the perioperative period. Therefore, in the
peri- and post-operative periods, it is necessary to take great care when
reducing the infusion dose.
PMID- 26442422
TI - [Management of a Patient with Aortic Stenosis Undergoing Lung Cancer Surgery].
AB - A 79-year-old man with aortic stenosis (AS) was scheduled for right middle
lobectomy under general anesthesia. AS is a significant risk factor for the
development of cardiac complications after noncardiac surgery. Anesthetic
management adjusting left ventricular preload and coload, and keeping sinus
rhythm was successful with no complications. But after moving back to the
intensive care unit after surgery, ECG showed paroxysmal complete
atrioventricular blocks and we inserted a temporary transvenous pacemaker
catheter. We should be very careful with not only the anesthetic but also
perioperative management of AS patient.
PMID- 26442423
TI - [Anesthetic Management of Three Patients with Chronic Inflammatory Demyelinating
Polyradiculoneuropathy].
AB - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronically
progressing or relapsing disease caused by immune-mediated peripheral neuropathy.
We report the anesthetic management of three CIDP patients who underwent elective
orthopedic surgeries. Owing to the risk of neuraxial anesthetics triggering
demyelination, general anesthesia was selected to avoid epidural or spinal
anesthesia or other neuraxial blockade. It was also judged prudent to avoid
prolonged perioperative immobilization, which might compress vulnerable
peripheral nerves. For Patient 1, general anesthesia was induced with propofol,
remifentanil, and sevoflurane, and was maintained with sevoflurane and
remifentanil. For Patients 2 and 3, general anesthesia was induced and maintained
with propofol and remifentanil. For tracheal intubation, under careful monitoring
with peripheral nerve stimulators, minimal doses of rocuronium (0.6-0.7 mg x kg(
1)) were administered. When sugammadex was administered to reverse the effect of
rocuronium, all patients rapidly regained muscular strength. Postoperative
courses were satisfactory without sequelae.
PMID- 26442424
TI - [Anesthetic Management of a Parturient with Eclampsia, Posterior Reversible
Encephalopathy Syndrome and Pulmonary Edema due to Pregnancy-induced
Hypertension].
AB - A 27-year-old woman with mental retardation was admitted to a nearby hospital for
an abrupt onset of seizure. Physical examination revealed remarkable hypertension
and pregnancy with estimated gestational age of 28th week. Severe pulmonary edema
and hypoxia led to a diagnosis of pregnancy-induced hypertension (PIH)
accompanied by eclampsia. She was orotracheally intubated because of refractory
seizure and hypoxemia, and transferred to our hospital for further treatment.
Besides severe hypoxia and hypercapnea, an enhanced lesion was detected in the
left posterior cerebrum by brain MRI. No abnormal findings were detected in the
fetus, with heart rate of 150 beats x min. She was diagnosed with posterior
reversible encephalopathy syndrome (PRES) caused by PIH and emergency cesarean
section under general anesthesia was scheduled. A male newborn was delivered with
Apgar score of 1/4 (1/5 min), followed by starting continuous infusion of
nicardipine for controlling hypertension. Chest X-P on completion of surgery
revealed remarkably alleviated pulmonary edema. She received intensive treatment
and continued positive pressure ventilation for four days after delivery. She
recovered with no neurological deficits and her child was well without any
complications.
PMID- 26442425
TI - [Problems with the Structure of a New Pentax-Airwayscope S200].
AB - BACKGROUND: Pentax-Airwayscope (AWS-S100) is useful for tracheal intubation, and
a new version S200 has recently been introduced to clinical practice. We felt
that S200 was more difficult than the S100 in attaching and detaching a single
use Introck blade. METHODS: In a randomized cross-over design, we compared S100
and S200, for the ease of attaching to and detaching from the Introck, fixation
of the Introck using the fixation ring of the main body, and insertion time.
RESULTS: Compared with S100, it was easier for S200 to fix the Introck using the
fixation ring (78% vs 72%) (P < 0.05), but it was more difficult for S200 to
attach (the incidence 43% vs 2%) and detach (53% vs 11%) the Introck (both P <
0.001). Insertion time was also significantly longer for S200 than S100 (median 9
[IQR : 6-19] s vs 4 [IQR : 3-6] s) (P < 0.001). The flexible scope of one of two
S200s kinked and was broken during attachment. CONCLUSIONS: It is necessary to
apply lubricant to the distal part of the scope to prevent damage to the scope.
PMID- 26442426
TI - [New Insights into Maternal Cardiopulmonary Resuscitation--Significance of
Simulation Research and Training].
AB - Pregnancy-related mortality, estimated to occur in approximately 1: 50,000
deliveries, is rare in developed countries. The 2010 American Heart Association
(AHA) Guidelines for Resuscitation emphasize the importance of high-quality chest
compression as a key determinant of successful cardiopulmonary resuscitation.
During pregnancy, the uterus can compress the inferior vena cava, impeding venous
return and thereby reducing stroke volume and cardiac output. To maximize the
effectiveness of chest compressions in pregnancy, the AHA guidelines recommend
the 27-30 degrees left-lateral tilt (LLT) position. When CPR is performed on
parturients in the LLT position, chest compressions will probably be more
effective if performed with the operator standing on the left side of the
patient. The videolaryngoscope Pentax-AWS Airwayscope (AWS) was found to be an
effective tool for airway management during chest compressions in 27 LLT
simulations, suggesting that the AWS may be a useful device for airway management
during maternal resuscitation.
PMID- 26442427
TI - [Evaluation of Knowledge on Cardiopulmonary Resuscitation for Pregnant Woman
among G2010 AHA-BLS-HCP Participants].
AB - Cardiac arrest during pregnancy is a rare event but it needs rapid and effective
cardiopulmonary resuscitation to prevent loss of two lives. In this questionnaire
survey, G2010 AHA-BLS Healthcare Provider Course participants answered four
questions about CPR caveats which should be considered during pregnancy. The
correct answer ratio is generally low among the four questions. Special situation
explanation addition such as left uterine displacement in the AHA-BLS healthcare
provider course may be needed for the empowerment of knowledge about
cardiopulmonary resuscitation during pregnancy.
PMID- 26442428
TI - [Tracheal Intubation Using the Pentax-AWS during Chest Compression: A Meta
analysis].
AB - BACKGROUND: The aim of this meta-analysis is to evaluate the efficacy of the
Pentax-AWS for tracheal intubation during chest compression, compared with that
of the Macintosh laryngoscope. METHODS: The systematic search, data extraction,
critical appraisal, and pooled analysis were performed according the PRISMA
statement. The relative risk (RR), mean difference (MD), and their corresponding
95% confidence intervals (CIs) were calculated by the Review Manager 5.2 software
for dichotomous and continuous outcomes, respectively. RESULTS: Twelve trials
included 424 tracheal intubations by Pentax-AWS and 421 tracheal intubations by
Macintosh laryngoscope. In studies examining novice laryngoscopists, successful
intubation (RR1.4, 95% CI 1.1-1.6, P < 0.0007) and time for instrumentation (MD
7.7 sec, 95% CI -10.1 sec--5.4 sec, P < 0.00001) were improved using the Pentax
AWS. With respect to experts' hands there was no difference between the two
devices in both of these outcomes. CONCLUSIONS: Compared to the Macintosh
laryngoscopy, Pentax-AWS offers advantages for novice laryngoscopists during
chest compression, while these benefits are not seen with experts' hands.
PMID- 26442429
TI - [Usefulness of ACUSON Freestyle (Siemens), Wireless Ultrasound System].
AB - The ACUSON Freestyle, the world's first wireless ultrasound system, was released
in April 2014. We assessed its usefulness, using it for central venous
cannulation, spinal anesthesia, brachial plexus or obturator nerve block, and for
the surgery of metastatic liver cancer as well as the spine. Generally, we could
use it smoothly in all situations. Comparing with the conventional ultrasound
system, the machine is big, heavy, with many buttons to operate. The main problem
with the conventional ultrasound system is the wire connecting probe and the main
system, which can interfere with procedures. With ACUSON Freestyle, we could
perform the nerve block and the central venous cannulation more easily with
little concern about contamination.
PMID- 26442430
TI - [Hospital Doctors Should Receive Lecture for Sedation According to Joint
Commission International].
AB - BACKGROUND: At our hospital, intending to obtaining an approval from the Joint
Commission International (JCI), we conducted a workshop on sedation for all staff
physicians. METHODS: A sedation instructor authorized by the Japanese Association
for Medical Simulation gave a lecture using the "practice guidelines for sedation
and administration of analgesics for non-anesthesiologists", revised in 2002 by
the American Society of Anesthesiologists, following which, a test using 10 true
false questions was conducted, while before and after the lecture a questionnaire
survey on the sedation lecture was carried out RESULTS: Among 191 physicians
attending the lecture, except for one person, 7 or more questions were answered
correctly. From the questionnaires, the sedation lectures were also generally
accepted favourably. In the test of understanding, the mistakes were mostly in
the sections on "sedation evaluation" "intraoperative monitoring" "pharmaceutical
knowledge" and "airway management methods". CONCLUSIONS: The sedation lecture in
the hospital was effective.
PMID- 26442431
TI - Physicians' views on pay-for-performance as a reimbursement model: a quantitative
study among Dutch surgical physicians.
AB - OBJECTIVES: To assess the views, knowledge, and experience of Dutch physicians
with regard to the general objectives and values of the pay-for-performance (P4P)
system, as the Dutch healthcare industry might find it useful, in terms of
governance, to explore this approach further. METHODS: A quantitative cross
sectional survey study was conducted among 48 physicians in surgical specialties
in the Netherlands between May 2014 and July 2014. The survey questionnaire was
designed to gather information regarding the intensity of feelings, on a 7-point
Likert scale, toward statements that address the P4P system. Confidence intervals
were calculated using the bootstrap technique with 1000 iterations. RESULTS:
Physicians see a positive value in P4P for their organizations rather than for
personal attainment (mean = 5.00; 95% CI = 4.62-5.39), even though they feared
that P4P might put financial pressure on them (mean = 5.03; 95% CI = 4.50-5.54).
They strongly share the view that other colleagues will resist adopting P4P as a
business model (mean = 5.74; 95% CI = 5.43-6.04). Respondents stated that they
would not leave their current jobs if P4P were to be incorporated in their
organization. CONCLUSIONS: Physicians see value in P4P for their organizations,
and consider that P4P could provide an incentive for improving medical outcomes.
There seems to be potential for the P4P system in the Netherlands as participants
expressed positive support for its values. There is an intersection of interests
between the value of P4P and the physicians' aim of achieving quality outcomes;
however, further studies would be needed to investigate perceptions about
specific design features in a larger sample. In addition, prior to implementing
P4P, broad education about the system should be provided in order to counteract
pre-conceptions and prevent resistance.
PMID- 26442432
TI - Chlorine Incorporation for Enhanced Performance of Planar Perovskite Solar Cell
Based on Lead Acetate Precursor.
AB - We show the effects of chlorine incorporation in the crystallization process of
perovskite film based on a lead acetate precursor. We demonstrate a fabrication
process for fast grain growth with highly preferred {110} orientation upon only 5
min of annealing at 100 degrees C. By studying the correlation between precursor
composition and morphology, the growth dynamic of perovskite film in the current
system is discussed. In particular, we found that both lead acetate precursor and
Cl incorporation are beneficial to perovskite growth. While lead acetate allows
fast crystallization process, Cl improves perovskite crystallinity. Planar
perovskite solar cells with optimized parameters deliver a best power conversion
efficiency of 15.0% and average efficiency of 14.0% with remarkable
reproducibility and good stability.
PMID- 26442433
TI - Does climate directly influence NPP globally?
AB - The need for rigorous analyses of climate impacts has never been more crucial.
Current textbooks state that climate directly influences ecosystem annual net
primary productivity (NPP), emphasizing the urgent need to monitor the impacts of
climate change. A recent paper challenged this consensus, arguing, based on an
analysis of NPP for 1247 woody plant communities across global climate gradients,
that temperature and precipitation have negligible direct effects on NPP and only
perhaps have indirect effects by constraining total stand biomass (Mtot ) and
stand age (a). The authors of that study concluded that the length of the growing
season (lgs ) might have a minor influence on NPP, an effect they considered not
to be directly related to climate. In this article, we describe flaws that
affected that study's conclusions and present novel analyses to disentangle the
effects of stand variables and climate in determining NPP. We re-analyzed the
same database to partition the direct and indirect effects of climate on NPP,
using three approaches: maximum-likelihood model selection, independent-effects
analysis, and structural equation modeling. These new analyses showed that about
half of the global variation in NPP could be explained by Mtot combined with
climate variables and supported strong and direct influences of climate
independently of Mtot , both for NPP and for net biomass change averaged across
the known lifetime of the stands (ABC = average biomass change). We show that lgs
is an important climate variable, intrinsically correlated with, and contributing
to mean annual temperature and precipitation (Tann and Pann ), all important
climatic drivers of NPP. Our analyses provide guidance for statistical and
mechanistic analyses of climate drivers of ecosystem processes for predictive
modeling and provide novel evidence supporting the strong, direct role of climate
in determining vegetation productivity at the global scale.
PMID- 26442434
TI - Impedance matching network for high frequency ultrasonic transducer for cellular
applications.
AB - An approach for the design of an impedance matching network (IMN) for high
frequency ultrasonic transducers with large apertures based on impedance analysis
for cellular applications is presented in this paper. The main objectives were to
maximize energy transmission from the excitation source to the ultrasonic
transducers for cell manipulation and to achieve low input parameters for the
safe operation of an ultrasonic transducer because the piezoelectric material in
high frequency ultrasonic transducers is prone to breakage due to its being
extremely thin. Two ultrasonic transducers, which were made of lithium niobate
single crystal with the thickness of 15 MUm, having apertures of 4.3 mm
(fnumber=1.23) and 2.6mm (fnumber=0.75) were tested. L-type IMN was selected for
high sensitivity and compact design of the ultrasonic transducers. The target
center frequency was chosen as the frequency where the electrical admittance
(|Y|) and phase angle (thetaz) from impedance analysis was maximal and zero,
respectively. The reference center frequency and reference echo magnitude were
selected as the center frequency and echo magnitude, measured by pulse-echo
testing, of the ultrasonic transducer without IMN. Initial component values and
topology of IMN were determined using the Smith chart, and pulse-echo testing was
analyzed to verify the performance of the ultrasonic transducers with and without
IMN. After several iterations between changing component values and topology of
IMN, and pulse-echo measurement of the ultrasonic transducer with IMN, optimized
component values and topology of IMN were chosen when the measured center
frequency from pulse-echo testing was comparable to the target frequency, and the
measured echo magnitude was at least 30% larger than the reference echo
magnitude. Performance of an ultrasonic transducer with and without IMN was
tested by observing a tangible dent on the surface of a plastic petridish and
single cell response after an acoustic pulse was applied on a target cell.
PMID- 26442435
TI - Investigation of complete bandgaps in a piezoelectric slab covered with
periodically structured coatings.
AB - The propagation of elastic waves in a piezoelectric slab covered with
periodically structured coatings or the so-called stubbed phononic crystal slab
is investigated. Four different models are selected and the effects of
distribution forms and geometrical parameters of the structured coatings on
complete bandgaps are discussed. The phononic crystal slab with symmetric
coatings can generate wider complete bandgaps while that with asymmetric coatings
is favorable for the generation of multi-bandgaps. The complete bandgaps, which
are induced by locally resonant effects, change significantly as the geometry of
the coatings changes. Moreover, the piezoelectric effects benefit the opening of
the complete bandgaps.
PMID- 26442436
TI - Ionic liquids as an electrolyte for the electro synthesis of organic compounds.
AB - The use of ionic liquids (ILs) as a solvent and an electrolyte for electro
organic synthesis has been reviewed. To date several ILs exist, however the ILs
based on tetraalkylammonium, pyrrolidinium, piperidinium and imidazolium cations
with BF4(-), PF6(-), and TFSI anions have been widely used and explored the most.
Electro organic synthesis in ionic liquid media leading to the synthesis of a
wide range of organic compounds has been discussed. Anodic oxidation or cathodic
reduction will generate radical cation or anion intermediates, respectively.
These radicals can undergo self coupling or coupling with other molecules
yielding organic compounds of interest. The cation of the IL is known to
stabilize the radical anion extensively. This stabilization effect has a specific
impact on the electrochemical CO2 reduction and coupling to various organics. The
relative stability of the intermediates in IL leads to the formation of specific
products in higher yields. Electrochemical reduction of imidazolium or thiazolium
based ILs generates N-heterocyclic carbenes that have been shown to catalyze a
wide range of base or nucleophile catalyzed organic reactions in IL media, an
aspect that falls into the category of organocatalysis. Electrochemical
fluorination or selective electrochemical fluorination is another fascinating
area that delivers selectively fluorinated organic products in Et3N.nHF or
Et4NF.nHF adducts (IL) via anodic oxidation. Oxidative polymerization in ILs has
been explored the most; although morphological changes were observed compared to
the conventional methods, polymers were obtained in good yields and in some cases
ILs were used as dopants to improve the desired properties.
PMID- 26442437
TI - Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium.
AB - The enteroendocrine system orchestrates how the body responds to the ingestion of
foods, employing a diversity of hormones to fine-tune a wide range of
physiological responses both within and outside the gut. Recent interest in gut
hormones has surged with the realization that they modulate glucose tolerance and
food intake through a variety of mechanisms, and such hormones are therefore
excellent therapeutic candidates for the treatment of diabetes and obesity.
Characterizing the roles and functions of different enteroendocrine cells is an
essential step in understanding the physiology, pathophysiology, and therapeutics
of the gut-brain-pancreas axis.
PMID- 26442438
TI - DNA Damage and Repair in Vascular Disease.
AB - DNA damage affecting both genomic and mitochondrial DNA is present in a variety
of both inherited and acquired vascular diseases. Multiple cell types show
persistent DNA damage and a range of lesions. In turn, DNA damage activates a
variety of DNA repair mechanisms, many of which are activated in vascular
disease. Such DNA repair mechanisms either stall the cell cycle to allow repair
to occur or trigger apoptosis or cell senescence to prevent propagation of
damaged DNA. Recent evidence has indicated that DNA damage occurs early, is
progressive, and is sufficient to impair function of cells composing the vascular
wall. The consequences of persistent genomic and mitochondrial DNA damage,
including inflammation, cell senescence, and apoptosis, are present in vascular
disease. DNA damage can thus directly cause vascular disease, opening up new
possibilities for both prevention and treatment. We review the evidence for and
the causes, types, and consequences of DNA damage in vascular disease.
PMID- 26442439
TI - Mammographic density and histopathologic characteristics of screen-detected
tumors in the Norwegian Breast Cancer Screening Program.
AB - BACKGROUND: High mammographic density might mask breast tumors, resulting in
delayed diagnosis or missed cancers. PURPOSE: To investigate the association
between mammographic density and histopathologic tumor characteristics
(histologic type, size, grade, and lymph node status) among women screened in the
Norwegian Breast Cancer Screening Program. MATERIAL AND METHODS: Information
about 1760 screen-detected ductal carcinoma in situ (DCIS) and 7366 invasive
breast cancers diagnosed among women aged 50-69 years, 1996-2010, was analyzed.
The screening mammograms were classified subjectively according to the amount of
fibroglandular tissue into fatty, medium dense, and dense by breast radiologists.
Chi-square test was used to compare the distribution of tumor characteristics by
mammographic density. Odds ratio (OR) of tumor characteristics by density was
estimated by means of logistic regression, adjusting for screening mode (screen
film and full-field digital mammography), and age. RESULTS: Mean and median tumor
size of invasive breast cancers was 13.8 and 12 mm, respectively, for women with
fatty breasts, and 16.2 and 14 mm for those with dense breasts. Lymph node
positive tumors were identified among 20.6% of women with fatty breasts compared
with 27.2% of those with dense breasts (P < 0.001). The proportion of DCIS was
significantly lower for women with fatty (15.8%) compared with dense breasts
(22.0%). Women with dense breasts had an increased risk of large (OR, 1.44; 95%
CI, 1.18-1.73) and lymph node positive tumors (OR, 1.26; 95% CI, 1.05-1.51)
compared with women with fatty and medium dense breasts. CONCLUSION: High
mammographic density was positively associated with tumor size and lymph node
positive tumors.
PMID- 26442440
TI - High-fat diet prevents adaptive peripartum-associated adrenal gland plasticity
and anxiolysis.
AB - Maternal obesity is associated with lower basal plasma cortisol levels and
increased risk of postpartum psychiatric disorders. Given that both obesity and
the peripartum period are characterized by an imbalance between
adrenocorticotropic hormone (ACTH) and cortisol, we hypothesized that the adrenal
glands undergo peripartum-associated plasticity and that such changes would be
prevented by a high-fat diet (HFD). Here, we demonstrate substantial peripartum
adrenal gland plasticity in the pathways involved in cholesterol supply for
steroidogenesis in female rats. In detail, the receptors involved in plasma lipid
uptake, low density lipoprotein (LDL) receptor (LDLR) and scavenger receptor
class B type 1 (SRB1), are elevated, intra-adrenal cholesterol stores are
depleted, and a key enzyme in de novo cholesterol synthesis,
hydroxymethylglutaryl coenzyme A reductase (HMGCR), is downregulated;
particularly at mid-lactation. HFD prevented the lactation-associated anxiolysis,
basal hypercorticism, and exaggerated the corticosterone response to ACTH.
Moreover, we show that HFD prevented the downregulation of adrenal cholesterol
stores and HMGCR expression, and LDLR upregulation at mid-lactation. These
findings show that the adrenal gland is an important regulator of peripartum
associated HPA axis plasticity and that HFD has maladaptive consequences for the
mother, partly by preventing these neuroendocrine and also behavioural changes.
PMID- 26442441
TI - Analysis of Proton NMR in Hydrogen Bonds in Terms of Lone-Pair and Bond Orbital
Contributions.
AB - NMR spectroscopic parameters of the proton involved in hydrogen bonding are
studied theoretically. The set of molecules includes systems with internal
resonance-assisted hydrogen bonds, internal hydrogen bonds but no resonance
stabilization, the acetic acid dimer (AAD), a DNA base pair, and the hydrogen
succinate anion (HSA). Ethanol and guanine represent reference molecules without
hydrogen bonding. The calculations are based on zero-point vibrationally averaged
molecular structures in order to include anharmonicity effects in the NMR
parameters. An analysis of the calculated NMR shielding and J-coupling is
performed in terms of "chemist's orbitals", that is, localized molecular orbitals
(LMOs) representing lone-pairs, atomic cores, and bonds. The LMO analysis
associates some of the strong de-shielding of the protons in resonance-assisted
hydrogen bonds with delocalization involving the pi-backbone. Resonance is also
shown to be an important factor causing de-shielding of the OH protons for AAD
and HSA, but not for the DNA base pair. Nitromalonamide (NMA) and HSA have
particularly strong hydrogen bonds exhibiting signs of covalency in the
associated J-couplings. The analysis results show how NMR spectroscopic
parameters that are characteristic for hydrogen bonded protons are influenced by
the geometry and degree of covalency of the hydrogen bond as well as intra- and
intermolecular resonance.
PMID- 26442442
TI - The management of tibial pilon fractures with the Ilizarov fixator: The role of
ankle arthroscopy.
AB - BACKGROUND: Pilon fractures usually result from high energy trauma, and are
commonly associated with extensive soft tissue damage which prevents the use of
open reduction and internal fixation. PURPOSE: This study was designed to
evaluate the use of the Ilizarov external fixator in the treatment of pilon
fractures of the ankle, and to determine whether arthroscopy of the ankle could
improve the outcome. METHODS: From February 2011 to May 2013 a total of 23
patients with unilateral closed pilon fractures were divided into two groups
treated with and without arthroscopy during fixation with the Ilizarov external
fixator. The fractures were classified according to the AO Rudi and Allgower
classification. Follow up ranged from 10 to 37 months with a mean of 18 months.
RESULTS: All cases were evaluated at follow up by the AOFAS and the Bone et al.
grading system. According to Bone et al. there were 3 cases excellent, 4 cases
good, 2 cases fair, and 2 cases poor in Group A (without arthroscopy), whereas
there were 4 cases excellent, 6 cases good, 2 cases fair in Group B (with
arthroscopy). The AOFAS score for Group A was 77.8+/-5.8, and for Group B was
78.4+/-6.9. CONCLUSION: We concluded that the Ilizarov external fixator is an
excellent method in treating pilon fractures as it minimizes the need for
extensive surgery. We also conclude that the use of arthroscopy during pilon
fracture fixation did not add statistically significant improvement to our
results and it needs longer term investigation to assess its advantage - if any -
to the final outcome. LEVEL OF EVIDENCE: level 2.
PMID- 26442443
TI - Methylation-mediated BMPER expression in fibroblast activation in vitro and lung
fibrosis in mice in vivo.
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease. Although the
pathogenesis is poorly understood, evidence suggests that genetic and epigenetic
alterations, such as DNA methylation, may play a key role. Bone morphogenetic
proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta)
superfamily and are important regulators in IPF. Here we identified BMP
endothelial cell precursor-derived regulator (BMPER) as a key regulator of
fibroblast activation. BMPER is a secreted glycoprotein that binds directly to
BMPs and may regulate TGF-beta/BMP signaling, but its role in lung fibrosis is
not clear. BMPER is highly expressed in human IPF lung fibroblasts compared to
normal lung fibroblasts. Demethylation agent 5'-azacytidine decreased BMPER
expression in fibroblasts, and attenuated the invasion and migration of IPF lung
fibroblasts. Furthermore, siRNA-mediated reduction of BMPER in the human lung
fibroblasts impaired cell migration and invasion. 5'-azacytidine treatment
additionally regulated BMPER expression and reduced lung fibrosis in mice in
vivo. These findings demonstrate that methylation of specific genes in
fibroblasts may offer a new therapeutic strategy for IPF by modulating fibroblast
activation.
PMID- 26442444
TI - Effect of Deletion of Ghrelin-O-Acyltransferase on the Pulsatile Release of
Growth Hormone in Mice.
AB - Ghrelin, a gut hormone originating from the post-translational cleavage of
preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor
1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of
ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring
selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of
preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes
to a decline in peak GH release; however, the selective contribution of
endogenous acyl-ghrelin to pulsatile GH release remains to be established. We
assessed the pulsatile release of GH in ad lib. fed male germline goat(-/-) mice,
extending measures to include mRNA for key hypothalamic regulators of GH release,
and peripheral factors that are modulated relative to GH release. The amount of
GH released was reduced in young goat(-/-) mice compared to age-matched wild-type
mice, whereas pulse frequency and irregularity increased. Altered GH release did
not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA
expression, or pituitary GH content, suggesting that loss of Goat does not
compromise canonical mechanisms that contribute to pituitary GH production and
release. Although loss of Goat resulted in an irregular pattern of GH release
(characterised by an increase in the number of GH pulses observed during extended
secretory events), this did not contribute to a change in the expression of
sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of
insulin-like growth factor (IGF)-1 were elevated in goat(-/-) mice. This rise in
circulating levels of IGF-1 was correlated with an increase in GH pulse
frequency, suggesting that sustained or increased IGF-1 release in goat(-/-) mice
may occur in response to altered GH release patterning. Our observations
demonstrate that germline loss of Goat alters GH release and patterning. Although
the biological relevance of altered GH secretory patterning remains unclear, we
propose that this may contribute to sustained IGF-1 release and growth in goat(-/
) mice.
PMID- 26442445
TI - Functional Outcomes of Isolated Medial Tibial Plateau Fractures.
AB - Isolated medial tibial plateau injuries are uncommon and underdescribed in the
literature. As such, the range of fracture severity and outcomes in comparison to
more frequently described tibial plateau fractures are lacking. To assess
outcomes of this rare injury, we compared two cohorts of patients. Overall, 27
patients who sustained 27 isolated medial plateau (Schatzker type IV) fractures
and 81 patients with 81 split depression lateral plateau (Schatzker type II)
fractures were compared. The outcomes were stratified by injury mechanism energy
and assessed with radiographs, clinical and arthroscopic examinations, and
functional status with the short musculoskeletal function assessment
questionnaire (SMFA). Overall, 52% of Schatzker type IV fractures versus 71% of
Schatzker type II were associated with high-energy injuries. Schatzker type IV
fractures were more often nondisplaced and amenable to being managed,
nonoperatively, 22 versus 6%, with excellent results. Schatzker type II fractures
had a corresponding higher proportion of postoperative articular step off greater
than 12 mm and poorer 12-month SMFA scores. Schatzker type IV fractures were more
often treated with an external fixator than Schatzker type II fractures (22 vs.
1%). Within Schatzker type IV fractures, high- versus low-energy injuries did not
differ significantly with regards to initial articular step off (4.2 vs. 5.1 mm),
ligamentous and meniscal injury, or SMFA outcomes. Isolated medial plateau
fractures had low- and high-energy patterns with differing management and
outcomes. Schatzker type IV fractures overall were associated with lower energy
mechanisms, less initial articular step off, and better functional outcomes than
Schatzker II comparisons in this cohort. The level of evidence is 4.
PMID- 26442446
TI - How good are routinely collected primary healthcare data for evaluating the
effectiveness of health service provision in a remote Aboriginal community?
AB - INTRODUCTION: Evaluation and monitoring of primary health care requires the
establishment and maintenance of an appropriate data system. This study reviews
the application and effectiveness of the Communicare data management system in
the delivery of health services to the Fitzroy Valley in the Kimberley region of
Western Australia. METHODS: Key demographic fields (sex, date of birth and
Aboriginal status) were examined for completeness (whether the date fields were
all completed and correct when compared with the paper file) while the
'conditions' field was examined for accuracy. Three chronic diseases (diabetes,
hypertension and chronic kidney disease) in adults and age-specific incidence for
four acute diseases (otitis media, gastroenteritis, lower respiratory tract
infection and skin infection) in children were included. RESULTS: Completeness of
chosen demographic fields was 100% for date of birth and sex and 98% for
Aboriginal status. Chronic conditions matched the paper files 100%, while the
recording of acute conditions was incomplete. Among older adults (>=55 years) the
prevalences of diabetes, chronic kidney disease and hypertension were 43%, 42%
and 39% respectively. Age-specific incidence of acute conditions was highest in
the 0-4 years age group where 25% had had at least one episode of otitis media
and 20% at least one episode of skin infection. CONCLUSIONS: The recording of
demographic and chronic disease data was complete, but lower for acute
conditions. Routinely collected data have a number of limitations, but
nonetheless are a feasible way to establish population health indices,
particularly for chronic diseases for this remote health service with minimal
expenditure and effort. These rates provide useful baselines for monitoring and
evaluating the impact of service delivery on health outcomes. This audit provides
an indication of the accuracy of routinely collected data in the electronic
system compared to the paper medical records, which have traditionally been
considered the gold standard. Data collected on chronic disease information were
accurate and clinically useful for health service planning, monitoring and
evaluation. Acute disease data were not accurate enough to be clinically useful.
PMID- 26442447
TI - Observation of tunable nonlinear effects in an analogue of superconducting
composite right/left hand filter.
AB - Artificial structures with negative permittivity or permeability have attracted
significant attention in the science community because they provide a pathway for
obtaining exotic electromagnetic properties not found in natural materials. At
the moment, the great challenge of these artificial structures in microwave
frequency exhibits a relatively large loss. It is well-known that superconducting
thin films have extremely low surface resistance. Hence, it is a good candidate
to resolve this constraint. Besides, the reported artificial structures with
negative permittivity or permeability are mainly focusing on linear regime of
wave propagation. However, any future effort in creating tunable structures would
require knowledge of nonlinear properties. In this work, a tunable
superconducting filter with composite right/left-hand transmission property is
proposed and fabricated. Its nonlinear effects on temperature and power are
studied by theoretical analysis and experiments.
PMID- 26442448
TI - Isolating Visual and Proprioceptive Components of Motor Sequence Learning in ASD.
AB - In addition to defining impairments in social communication skills, individuals
with autism spectrum disorder (ASD) also show impairments in more basic sensory
and motor skills. Development of new skills involves integrating information from
multiple sensory modalities. This input is then used to form internal models of
action that can be accessed when both performing skilled movements, as well as
understanding those actions performed by others. Learning skilled gestures is
particularly reliant on integration of visual and proprioceptive input. We used a
modified serial reaction time task (SRTT) to decompose proprioceptive and visual
components and examine whether patterns of implicit motor skill learning differ
in ASD participants as compared with healthy controls. While both groups learned
the implicit motor sequence during training, healthy controls showed robust
generalization whereas ASD participants demonstrated little generalization when
visual input was constant. In contrast, no group differences in generalization
were observed when proprioceptive input was constant, with both groups showing
limited degrees of generalization. The findings suggest, when learning a motor
sequence, individuals with ASD tend to rely less on visual feedback than do
healthy controls. Visuomotor representations are considered to underlie imitative
learning and action understanding and are thereby crucial to social skill and
cognitive development. Thus, anomalous patterns of implicit motor learning, with
a tendency to discount visual feedback, may be an important contributor in core
social communication deficits that characterize ASD. Autism Res 2016, 9: 563-569.
(c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 26442450
TI - Role of DnaK in HspR-HAIR interaction of Mycobacterium tuberculosis.
AB - Heat shock proteins (Hsps) are a highly conserved family of proteins. The
regulation of expression of Hsps in Mycobacterium tuberculosis, is regulated both
positively and negatively by alternate sigma factors and transcriptional DNA
repressors, respectively. HspR is a negative regulator of expression of hsps,
DnaK, ClpB, and Acr2 in M. tuberculosis. In this study, we expressed the M.
tuberculosis HspR (MtHspR) in E. coli, and functionally characterized it. MtHspR
independently bound to its putative cognate DNA, the HAIR element. MtHspR was
found to exist in a dynamic mixture of dimeric and monomeric protein and presence
of salt led to the formation of trimers which lacked the DNA binding activity.
MtHspR was found to be heat stable with a Tm of 66 degrees C. HspR-HAIR binding
was stable upto 60 degrees C suggesting that MtHspR is not the heat stress
sensor. Mycobacterial DnaK was found to interact directly with MtHspR-HAIR
complex in vitro in an ATP independent manner. The DnaK-HspR-HAIR binding pattern
altered at high temperatures in the presence of aggregated alpha-casein
substrate, suggesting that DnaK may indirectly be responding to heat stress in a
feedback loop mechanism.
PMID- 26442451
TI - A structural and spectrophotometric study on the complexation of Am(III) with
TMOGA in comparison with the extracted complex of DMDOOGA.
AB - Complexation of Am(iii) with tetramethyl-3-oxa-glutaramide (TMOGA, L(I)) is
studied by spectrophotometric titrations and single crystal X-ray diffraction.
Three successive complex species, [AmL(I)](3+), [AmL](3+), and [AmL](3+), have
been identified and their stability constants are calculated to be 3.71 +/-
0.012, 5.95 +/- 0.021, and 6.93 +/- 0.034 respectively, from the absorption
spectra collected from the titrations of Am(iii) with L(I) at 25 degrees C in 1
M NaNO3. Single crystals of AmL(ClO4)3 have been grown from a HClO4 solution
containing Am(3+) and L(I). The crystal structure of AmL(ClO4)3 shows that
Am(iii) is coordinated by nine oxygen atoms from three L(I) ligands. The
deconvoluted UV-Vis absorption spectrum of [AmL](3+) in aqueous solution is
nearly identical to the diffusion reflectance spectrum of AmL(ClO4)3 in the solid
state, indicating that the coordination geometry of the complexes is nearly the
same. In addition, to provide parallels to solvent exaction, the extracted
Am(iii) complex with N,N'-dimethyl-N,N'-dioctyl-3-oxa-glutaramide (DMDOOGA,
L(II)) is also prepared and studied using spectrophotometry. The similarity in UV
Vis absorption of the extracted complex of Am(iii) with L(II) and [AmL](3+)
suggests that the Am(iii) ion is also coordinated by three tridentate L(II)
ligands existing as [AmL](3+) in the organic phase of solvent extraction.
PMID- 26442449
TI - Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and
shuttle microRNAs.
AB - Mesenchymal stem cells (MSCs) and macrophages are fundamental components of the
stem cell niche and function coordinately to regulate haematopoietic stem cell
self-renewal and mobilization. Recent studies indicate that mitophagy and healthy
mitochondrial function are critical to the survival of stem cells, but how these
processes are regulated in MSCs is unknown. Here we show that MSCs manage
intracellular oxidative stress by targeting depolarized mitochondria to the
plasma membrane via arrestin domain-containing protein 1-mediated microvesicles.
The vesicles are then engulfed and re-utilized via a process involving fusion by
macrophages, resulting in enhanced bioenergetics. Furthermore, we show that MSCs
simultaneously shed micro RNA-containing exosomes that inhibit macrophage
activation by suppressing Toll-like receptor signalling, thereby de-sensitizing
macrophages to the ingested mitochondria. Collectively, these studies
mechanistically link mitophagy and MSC survival with macrophage function, thereby
providing a physiologically relevant context for the innate immunomodulatory
activity of MSCs.
PMID- 26442452
TI - The NINDS Parkinson's disease biomarkers program.
AB - BACKGROUND: Neuroprotection for Parkinson's disease (PD) remains elusive.
Biomarkers hold the promise of removing roadblocks to therapy development. The
National Institute of Neurological Disorders and Stroke has therefore established
the Parkinson's Disease Biomarkers Program to promote discovery of PD biomarkers
for use in phase II and III clinical trials. METHODS: Using a novel consortium
design, the Parkinson's Disease Biomarker Program is focused on the development
of clinical and laboratory-based biomarkers for PD diagnosis, progression, and
prognosis. Standardized operating procedures and pooled reference samples were
created to allow cross-project comparisons and assessment of batch effects. A web
based Data Management Resource facilitates rapid sharing of data and biosamples
across the research community for additional biomarker projects. RESULTS: Eleven
consortium projects are ongoing, seven of which recruit participants and obtain
biosamples. As of October 2014, 1,082 participants have enrolled (620 PD, 101
with other causes of parkinsonism, 23 essential tremor, and 338 controls), 1,040
of whom have at least one biosample. Six thousand eight hundred ninety-eight
total biosamples are available from baseline, 6-, 12-, and 18-month visits: 1,006
DNA, 1,661 RNA, 1,419 whole blood, 1,382 plasma, 1,200 serum, and 230
cerebrospinal fluid (CSF). Quality control analysis of plasma, serum, and CSF
samples indicates that almost all samples are high quality (24 of 2,812 samples
exceed acceptable hemoglobin levels). CONCLUSIONS: By making samples and data
widely available, using stringent operating procedures based on existing
standards, hypothesis testing for biomarker discovery, and providing a resource
that complements existing programs, the Parkinson's Disease Biomarker Program
will accelerate the pace of PD biomarker research. (c) 2015 International
Parkinson and Movement Disorder Society.
PMID- 26442453
TI - Generation of Oxtr cDNA(HA)-Ires-Cre Mice for Gene Expression in an Oxytocin
Receptor Specific Manner.
AB - The neurohypophysial hormone oxytocin (OXT) and its receptor (OXTR) have critical
roles in the regulation of pro-social behaviors, including social recognition,
pair bonding, parental behavior, and stress-related responses. Supporting this
hypothesis, a portion of patients suffering from autism spectrum disorder have
mutations, such as single nucleotide polymorphisms, or epigenetic modifications
in their OXTR gene. We previously reported that OXTR-deficient mice exhibit
pervasive social deficits, indicating the critical role of OXTR in social
behaviors. In the present study, we generated Oxtr cDNA(HA)-Ires-Cre knock-in
mice, expressing both OXTR and Cre recombinase under the control of the
endogenous Oxtr promoter. Knock-in cassette of Oxtr cDNA(HA)-Ires-Cre consisted
of Oxtr cDNA tagged with the hemagglutinin epitope at the 3' end (Oxtr cDNA(HA)),
internal ribosomal entry site (Ires), and Cre. Cre was expressed in the uterus,
mammary gland, kidney, and brain of Oxtr cDNA(HA)-Ires-Cre knock-in mice.
Furthermore, the distribution of Cre in the brain was similar to that observed in
Oxtr-Venus fluorescent protein expressing mice (Oxtr-Venus), another animal model
previously generated by our group. Social behavior of Oxtr cDNA(HA)-Ires-Cre
knock-in mice was similar to that of wild-type animals. We demonstrated that this
construct is expressed in OXTR-expressing neurons specifically after an infection
with the recombinant adeno-associated virus carrying the flip-excision switch
vector. Using this system, we showed the transport of the wheat-germ agglutinin
tracing molecule from the OXTR-expressing neurons to the innervated neurons in
knock-in mice. This study might contribute to the monosynaptic analysis of
neuronal circuits and to the optogenetic analysis of neurons expressing OXTR.
PMID- 26442454
TI - An Unusual Right Atrial Mass: A Misdiagnosis Identified by Intraoperative
Transesophageal Echocardiography.
PMID- 26442455
TI - Sequential screening to predict symptomatic pulmonary thromboembolism after
gynecologic surgery in Nara, Japan.
AB - OBJECTIVE: To evaluate a sequential screening method's efficacy in predicting
symptomatic pulmonary thromboembolism (PTE) after gynecologic surgery. METHODS: A
prospective study employing a two-stage screening process was conducted among
consecutive asymptomatic adults who underwent outpatient evaluation for
gynecologic surgery at Nara Medical University Hospital, Japan, between April 1,
2004, and December 31, 2013. Patients with a preoperative plasma D-dimer level
greater than or equal to 1.0MUg/mL underwent compression ultrasonography of the
lower extremities. The primary outcome measure was postoperative detection of
symptomatic PTE. RESULTS: Overall, 1729 patients were included. The mean D-dimer
level was 1.7+/-3.3MUg/mL. Compression ultrasonography was conducted among 470
(27.1%) patients with positive D-dimer test results; symptomatic deep vein
thrombosis (DVT) was preoperatively detected among 94 (20.0%) of them. Patients
with DVT (n=94) had higher D-dimer levels than patients (n=1635) without (7.8+/
12.8MUg/mL vs 1.1+/-1.8MUg/mL; P<0.001). Despite anticoagulant therapy,
symptomatic PTE was detected postoperatively among two of these 94 patients.
Symptomatic PTE was also detected among four of 376 patients with positive D
dimer test results but no evidence of DVT by ultrasonography. No clinical onset
of postoperative PTE was observed among 1259 patients with D-dimer levels below
the cut-off value. CONCLUSION: The PROVEN screening strategy (Preoperative
surveillance using a sequential strategy) was ineffective at predicting
postoperative symptomatic PTE.
PMID- 26442456
TI - A strategy to discover decoy chemokine ligands with an anti-inflammatory
activity.
AB - Excessive signaling by chemokines has been associated with chronic inflammation
or cancer, thus attracting substantial attention as promising therapeutic
targets. Inspired by chemokine-clearing molecules shaped by pathogens to escape
the immune system, we designed a generic screening assay to discover chemokine
neutralizing molecules (neutraligands) and unambiguously distinguish them from
molecules that block the receptor (receptor antagonists). This assay, called TRIC
r, combines time-resolved intracellular calcium recordings with pre-incubation of
bioactive compounds either with the chemokine or the receptor-expressing cells.
We describe here the identification of high affinity neutraligands of CCL17 and
CCL22, two chemokines involved in the Th2-type of lung inflammation. The decoy
molecules inhibit in vitro CCL17- or CCL22-induced intracellular calcium
responses, CCR4 endocytosis and human T cell migration. In vivo, they inhibit
inflammation in a murine model of asthma, in particular the recruitment of
eosinophils, dendritic cells and CD4(+)T cells. Altogether, we developed a
successful strategy to discover as new class of pharmacological tools to potently
control cell chemotaxis in vitro and in vivo.
PMID- 26442458
TI - Correlation of the New York Heart Association Classification and the 6-Minute
Walk Distance: A Systematic Review.
AB - BACKGROUND: Functional status assessment is the cornerstone of heart failure
management and trials. The New York Heart Association (NYHA) classification and 6
minute walk distance (6MWD) are commonly used tools; however, the correlation
between them is not well understood. HYPOTHESIS: We hypothesised that the
relationship between the NYHA classification and 6MWD might vary across studies.
METHODS: A systematic literature search was performed to identify all studies
reporting both NYHA class and 6MWD. Two reviewers independently assessed study
eligibility and extracted data. Thirty-seven studies involving 5678 patients were
included. RESULTS: There was significant heterogeneity across studies in 6MWD
within all NYHA classes: I (n = 16, Q = 934.2; P < 0.001), II (n = 25, Q =
1658.3; P < 0.001), III (n = 30, Q = 1020.1; P < 0.001), and IV (n = 6, Q =
335.5; P < 0.001). There was no significant difference in average 6MWD between
NYHA I and II (420 m vs 393 m; P = 0.416). There was a significant difference in
average 6MWD between NYHA II and III (393 m vs 321 m; P = 0.014) and III and IV
(321 m vs 224 m; P = 0.027). This remained significant after adjusting for region
of study, age, and sex. CONCLUSIONS: Although there is an inverse correlation
between NYHA II-IV and 6MWD, there is significant heterogeneity across studies in
6MWD within each NYHA class and overlap in 6MWD between NYHA I and II. The NYHA
classification performs well in more symptomatic patients (NYHA III/IV) but less
so in asymptomatic/mildly symptomatic patients (NYHA I/II). Nonetheless, the NYHA
classification is an easily applied first-line tool in everyday clinical
practice, but its potential subjectivity should be considered when performing
comparisons across studies.
PMID- 26442457
TI - Monocyte enhancers are highly altered in systemic lupus erythematosus.
AB - OBJECTIVE: Histone modifications set transcriptional competency and can
perpetuate pathologic expression patterns. We defined systemic lupus
erythematosus (SLE)-specific changes in H3K4me3 and K3K27me3, histone marks of
gene activation and repression, respectively. METHODS: We used ChIP-seq to define
histone modifications in monocytes from SLE patients and controls. RESULTS: Both
promoters and enhancers exhibited significant changes in histone methylation in
SLE. Regions with differential H3K4me3 in SLE were significantly enriched in
potential interferon-related transcription factor binding sites and pioneer
transcription factor sites. CONCLUSION: Enhancer activation defines the character
of the cell and our data support extensive disease effects in monocytes, a
particularly plastic lineage. Type I interferons not only drive altered gene
expression but may also alter the character of the cell through chromatin
modifications.
PMID- 26442459
TI - Patient volumes and pre- and postdischarge postpartum infection: A retrospective
cohort study.
AB - BACKGROUND: To examine the association between hospital and clinician obstetric
volume and postpartum infection risk in the pre- and postdischarge periods.
METHODS: We used data from the 2011 New York State Inpatient and Emergency
Department Databases to fit generalized estimating equation models to examine the
effect of hospital and clinician obstetric volume on infection before discharge
and in the 30 days after discharge after delivery. RESULTS: Higher clinician
volume was associated with lower predischarge infection risk (odds ratio [OR] for
first vs third quartile was 0.84; 95% confidence interval [CI], 0.77-0.98). There
was an uncertain trend toward higher predischarge infection risk in higher volume
hospitals (OR for first vs third quartile was 1.36; 95% CI, 0.79-2.34). We found
no associations between patient volumes and postdischarge infections; however,
power was insufficient to rule out small associations. The joint association of
hospital and clinician volumes with postdischarge infection appeared
submultiplicative (product term OR = 0.95; 95% CI, 0.92-0.98). CONCLUSION: This
study adds to the evidence that hospital obstetric volume is positively
associated with predischarge postpartum infections, whereas clinician volume may
be negatively associated with those predischarge infections. The associations
between hospital obstetric volume and postdischarge infection appear to differ.
These results underscore the importance of including postdischarge follow-up in
hospital-based studies of postpartum infection.
PMID- 26442460
TI - Poor hand hygiene by college students linked to more occurrences of infectious
diseases, medical visits, and absence from classes.
AB - BACKGROUND: Proper hand hygiene has been linked to lower susceptibility to
infectious diseases in many types of communities, but it has not been well
established on college campuses. This study investigated the hand hygiene
statuses of college students and their occurrences in relation to infectious
diseases, medical visits, and absence from classes or work. It also examined the
effects of education on handwashing technique to improve hand hygiene. METHODS:
College students enrolled at a university in Northwestern Ohio were recruited as
study subjects. Microbial samples were collected 3 times from each of the 220
valid volunteers before washing their hands, after washing with their own
procedures, and after washing with a procedure recommended by the Centers for
Disease Control and Prevention (CDC). Each volunteer also answered a survey
including questions on their health conditions, medical visits, and absence from
classes or work. RESULTS: Hands of 57.7% volunteers were colonized by an
uncountable number of microbial colonies, which were significantly linked to more
occurrences to infectious diseases (P < .05), medical visits (P < .05), and
arguably more absence from classes or work (P = .09). The handwashing procedure
provided by the CDC significantly improved hand hygiene. CONCLUSION: It is
critical to promote education on proper handwashing in colleges, in grade
schools, and at home to improve health and learning outcomes.
PMID- 26442461
TI - Immunity of nursing students to measles, mumps, rubella, and varicella in Yozgat,
Turkey.
AB - Measles, mumps, rubella, and varicella (MMRV) are vaccine-preventable diseases.
The aim of this study was to determine the vaccination status of first-year
nursing students in Turkey. The sample used was 180 students and immunoglobulin G
antibodies against MMRV viruses were determined quantitatively by enzyme-linked
immunosorbent assay. Immunity rates to MMRV were 82.8%, 83.3%, 98.3%, and 100%,
respectively. The results of this study showed that all of the students were
immune to varicella and 32.8% of the students were not immune to at least 1 of
the viruses covered by the measles, mumps, and rubella vaccine.
PMID- 26442462
TI - Infection control strategies that successfully controlled an outbreak of
Mycobacterium abscessus at a cystic fibrosis center.
AB - BACKGROUND: Mycobacterium abscessus infection in patients with cystic fibrosis
(CF) can result in accelerated clinical decline and the potential for direct or
indirect transmission between patients has been recently demonstrated. Data on
the outcomes of M abscessus outbreaks and the efficacy of specific infection
control procedures in patients with CF remain limited. This study provides follow
up from an outbreak of pulmonary M abscessus in our center, highlighting outcomes
and strategies that appear to have prevented further spread of the organism.
METHODS: Data from our adult CF center (1989-2015) were analyzed, including chart
reviews of all patients with positive mycobacterial sputum cultures, cultures
from environment surfaces, and epidemiologic evaluation of infected patients.
Following an M abscessus outbreak in 2009, infection control policies were
intensified based on CF guidelines and surveillance data were collected and
reviewed. RESULTS: Five cases of M abscessus were involved in the outbreak; 3
patients died during follow-up. An environment search failed to reveal an
intermediary source of transmission between patients. After implementation of
infection control measures composed of staff/patient education, environment
sterilization, and patient isolation, no new cases were detected. CONCLUSIONS:
Direct or indirect patient-to-patient transmission of M abscessus is a threat in
the CF population. A multifaceted infection control strategy based on CF
guidelines was effective in halting transmission in our center.
PMID- 26442463
TI - Correction: Stereoselective synthesis of the head group of archaeal phospholipid
PGP-Me to investigate bacteriorhodopsin-lipid interactions.
AB - Correction for 'Stereoselective synthesis of the head group of archaeal
phospholipid PGP-Me to investigate bacteriorhodopsin-lipid interactions' by Jin
Cui, et al., Org. Biomol. Chem., 2015, DOI: 10.1039/c5ob01252j.
PMID- 26442465
TI - Transient apical pseudohypertophy due to myocardial edema in patients with
Takotsubo syndrome.
PMID- 26442464
TI - Learning from the other limb's experience: sharing the 'trained' M1
representation of the motor sequence knowledge.
AB - KEY POINTS: Participants were scanned during the untrained-hand performance of a
motor sequence, intensively trained a day earlier, and also a similarly
constructed but novel, untrained sequence. The superior performance levels for
the trained, compared to the untrained sequence, were associated with a greater
magnitude of activity within the primary motor cortex (M1), bilaterally, for the
trained sequence. The differential responses in the 'trained' M1, ipsilateral to
the untrained hand, were positively correlated with experience-related
differences in the functional connectivity between the 'trained' M1 and (1) its
homologue and (2) the dorsal premotor cortex (PMd) within the contralateral
hemisphere. No significant correlation was evident between experience-related
differences in M1 - M1 and M1 - PMd connectivity measures. These results suggest
that the transfer of sequence-specific information between the two primary motor
cortices is predominantly mediated by excitatory mechanisms driven by the
'trained' M1 via two independent neural pathways. Following unimanual training on
a novel sequence of movements, sequence-specific performance may improve
overnight not only in the trained hand, but also in the hand afforded no actual
physical experience. It is not clear, however, how transfer to the untrained hand
is achieved. In the present study, we examined whether and how interaction
between the two primary motor cortices contributes to the performance of a
sequence of movements, extensively trained the day before, by the untrained hand.
Accordingly, we studied participants during the untrained-hand performance of a
finger-to-thumb opposition sequence (FOS), intensively trained a day earlier (T
FOS), and a similarly constructed, but novel, untrained FOS (U-FOS). Changes in
neural signals driven by task performance were assessed using functional magnetic
resonance imaging. To minimize potential differences as a result of the rate of
sequence execution per se, participants performed both sequences at an identical
paced rate. The analyses showed that the superior fluency in executing the T-FOS
compared to the U-FOS was associated with higher activity within the primary
motor cortex (M1), bilaterally, for the T-FOS. The differential responses in the
'trained' M1 were positively correlated with experience-related differences in
the functional connectivity between the 'trained' M1 and (1) its left homologue
and (2) the left dorsal premotor cortex. However, no significant correlation was
evident between the changes in connectivity in these two routes. These results
suggest that the transfer of sequence-specific information between the two
primary motor cortices is predominantly mediated by excitatory mechanisms driven
by the 'trained' M1 via at least two independent neural pathways.
PMID- 26442466
TI - Metric qualities of the cognitive behavioral assessment for outcome evaluation to
estimate psychological treatment effects.
AB - BACKGROUND: Cognitive behavioral assessment for outcome evaluation was developed
to evaluate psychological treatment interventions, especially for counseling and
psychotherapy. It is made up of 80 items and five scales: anxiety, well-being,
perception of positive change, depression, and psychological distress. The aim of
the study was to present the metric qualities and to show validity and
reliability of the five constructs of the questionnaire both in nonclinical and
clinical subjects. METHODS: Four steps were completed to assess reliability and
factor structure: criterion-related and concurrent validity, responsiveness, and
convergent-divergent validity. A nonclinical group of 269 subjects was enrolled,
as was a clinical group comprising 168 adults undergoing psychotherapy and
psychological counseling provided by the Italian public health service. RESULTS:
Cronbach's alphas were between 0.80 and 0.91 for the clinical sample and between
0.74 and 0.91 in the nonclinical one. We observed an excellent structural
validity for the five interrelated dimensions. The clinical group showed higher
scores in the anxiety, depression, and psychological distress scales, as well as
lower scores in well-being and perception of positive change scales than those
observed in the nonclinical group. Responsiveness was large for the anxiety, well
being, and depression scales; the psychological distress and perception of
positive change scales showed a moderate effect. CONCLUSION: The questionnaire
showed excellent psychometric properties, thus demonstrating that the
questionnaire is a good evaluative instrument, with which to assess pre- and post
treatment outcomes.
PMID- 26442467
TI - Sargaquinoic acid attenuates inflammatory responses by regulating NF-kappaB and
Nrf2 pathways in lipopolysaccharide-stimulated RAW 264.7 cells.
AB - Myagropsis myagroides, a brown alga, showed strong anti-inflammatory activities
in the previous studies. In this study, we isolated a strong anti-inflammatory
compound, sargaquinoic acid (SQA), from M. myagroides and investigated the anti
inflammatory action using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.
SQA suppressed the production of inducible nitric oxide synthase and
cyclooxygenase-2 in LPS-stimulated cells as well as that of reactive oxygen
species. As a result, SQA inhibited the production of NO, prostaglandin E2, and
pro-inflammatory cytokines. LPS-induced transcriptional activation of nuclear
factor-kappaB (NF-kappaB) was remarkably inhibited by SQA treatment through the
prevention of inhibitor kappaB-alpha degradation. The regulation of NF-kappaB
activation was also mediated by the phosphorylation of ERK and Akt in LPS
stimulated RAW 264.7 cells. Moreover, SQA induced the production of heme
oxygenase 1 via activation of transcription factor Nrf2. These results indicate
that SQA inhibits the LPS-induced expression of inflammatory mediators via
suppression of ERK and Akt-mediated NF-kappaB pathway as well as up-regulation of
Nrf2/HO-1 pathway, indicating that SQA has a potential therapeutic and preventive
application in various inflammatory diseases.
PMID- 26442468
TI - A proteomic glimpse into human ureter proteome.
AB - Urine has evolved as one of the most important biofluids in clinical proteomics
due to its noninvasive sampling and its stability. Yet, it is used in clinical
diagnostics of several disorders by detecting changes in its components including
urinary protein/polypeptide profile. Despite the fact that majority of proteins
detected in urine are primarily originated from the urogenital (UG) tract,
determining its precise source within the UG tract remains elusive. In this
article, we performed a comprehensive analysis of ureter proteome to assemble the
first unbiased ureter dataset. Next, we compared these data to urine, urinary
exosome, and kidney mass spectrometric datasets. Our result concluded that among
2217 nonredundant ureter proteins, 751 protein candidates (33.8%) were detected
in urine as urinary protein/polypeptide or exosomal protein. On the other hand,
comparing ureter protein hits (48) that are not shown in corresponding databases
to urinary bladder and prostate human protein atlas databases pinpointed 21
proteins that might be unique to ureter tissue. In conclusion, this finding
offers future perspectives for possible identification of ureter disease
associated biomarkers such as ureter carcinoma. In addition, the ureter proteomic
dataset published in this article will provide a valuable resource for
researchers working in the field of urology and urine biomarker discovery. All MS
data have been deposited in the ProteomeXchange with identifier PXD002620
(http://proteomecentral.proteomexchange.org/dataset/PXD002620).
PMID- 26442470
TI - Increasing Relationship Between Negative Emotionality and Conduct Problems During
Childhood: A Cross-Sectional Behavioral Genetic Analysis.
AB - Age difference in the etiology of the relationship between childhood negative
emotionality (NE) and conduct problems (CP) has not been previously investigated.
Mothers of 662 pairs of twins completed questions on the emotionality (NE) scale
of the EAS temperament survey and the CP scale of the Strengths and Difficulties
Questionnaires (SDQ) via a telephone interview. Twin data were analyzed
separately in younger (ages 3 to 7 years; mostly pre-schoolers) and older
children (ages 8 to 13 years; mostly elementary school children). The phenotypic
correlation between NE and CP increased from 0.33 among younger twins to 0.43
among older twins. Bivariate model-fitting analysis was performed to determine
age difference in the etiology of the relationship between NE and CP. Among
younger twins, the correlation between NE and CP was entirely explained by
additive genetic factors common to NE and CP. Among older children, however, a
small but significant amount of unique environmental correlation emerged to
account for about 47% of the phenotypic correlation between NE and CP. The
remaining 53% of the phenotypic correlation was due to shared additive genetic
factors. We speculate that environmental factors associated with school
adjustment may exert influences on the relationship between NE and CP among
elementary school children.
PMID- 26442469
TI - Rhesus monkey model of liver disease reflecting clinical disease progression and
hepatic gene expression analysis.
AB - Alcoholic liver disease (ALD) is a significant public health issue with heavy
medical and economic burdens. The aetiology of ALD is not yet completely
understood. The development of drugs and therapies for ALD is hampered by a lack
of suitable animal models that replicate both the histological and metabolic
features of human ALD. Here, we characterize a rhesus monkey model of alcohol
induced liver steatosis and hepatic fibrosis that is compatible with the clinical
progression of the biochemistry and pathology in humans with ALD. Microarray
analysis of hepatic gene expression was conducted to identify potential molecular
signatures of ALD progression. The up-regulation of expression of hepatic genes
related to liver steatosis (CPT1A, FASN, LEPR, RXRA, IGFBP1, PPARGC1A and SLC2A4)
was detected in our rhesus model, as was the down-regulation of such genes
(CYP7A1, HMGCR, GCK and PNPLA3) and the up-regulation of expression of hepatic
genes related to liver cancer (E2F1, OPCML, FZD7, IGFBP1 and LEF1). Our results
demonstrate that this ALD model reflects the clinical disease progression and
hepatic gene expression observed in humans. These findings will be useful for
increasing the understanding of ALD pathogenesis and will benefit the development
of new therapeutic procedures and pharmacological reagents for treating ALD.
PMID- 26442471
TI - Effect of ocean acidification on growth and otolith condition of juvenile scup,
Stenotomus chrysops.
AB - Increasing amounts of atmospheric carbon dioxide (CO2) from human industrial
activities are causing changes in global ocean carbonate chemistry, resulting in
a reduction in pH, a process termed "ocean acidification." It is important to
determine which species are sensitive to elevated levels of CO2 because of
potential impacts to ecosystems, marine resources, biodiversity, food webs,
populations, and effects on economies. Previous studies with marine fish have
documented that exposure to elevated levels of CO2 caused increased growth and
larger otoliths in some species. This study was conducted to determine whether
the elevated partial pressure of CO2 (pCO2) would have an effect on growth,
otolith (ear bone) condition, survival, or the skeleton of juvenile scup,
Stenotomus chrysops, a species that supports both important commercial and
recreational fisheries. Elevated levels of pCO2 (1200-2600 MUatm) had no
statistically significant effect on growth, survival, or otolith condition after
8 weeks of rearing. Field data show that in Long Island Sound, where scup spawn,
in situ levels of pCO2 are already at levels ranging from 689 to 1828 MUatm due
to primary productivity, microbial activity, and anthropogenic inputs. These
results demonstrate that ocean acidification is not likely to cause adverse
effects on the growth and survivability of every species of marine fish. X-ray
analysis of the fish revealed a slightly higher incidence of hyperossification in
the vertebrae of a few scup from the highest treatments compared to fish from the
control treatments. Our results show that juvenile scup are tolerant to increases
in seawater pCO2, possibly due to conditions this species encounters in their
naturally variable environment and their well-developed pH control mechanisms.
PMID- 26442472
TI - Structural phase transitions and photoluminescence properties of Eu(3+) doped
Ca(2-x)BaxLaNbO6 phosphors.
AB - Crystal structures of the series of double perovskites Ca(2-x)BaxLaNbO6:Eu(3+)
phosphors have been examined by powder X-ray diffraction and Rietveld
refinements. Ca2LaNbO6 has a monoclinic (P21/n) and Ba2LaNbO6 has a monoclinic
(C2/m) structure. The structural phases of Ca(2-x)BaxLaNbO6:Eu(3+) samples are
divided into three sections depending on different Ca/Ba ratios: (1) monoclinic
phase (P21/n) as Ca2LaNbO6 in the range of x = 0-0.1, (2) mixed phases containing
Ca2LaNbO6 and Ba2LaNbO6 between 0.15 and 1.2, and (3) monoclinic phase (C2/m) as
Ba2LaNbO6 for x = 1.4-2. Eu(3+) ions act as the structural probes to study the
structural phase transitions, and the evolution of the photoluminescence
properties and thermal stability behaviours has been also comparatively
investigated depending on different structural symmetries from Ca2LaNbO6 to
Ba2LaNbO6 phase. The strong red emission from (5)D0-(7)F2 peaking at 618 nm can
be found in Ca2LaNbO6:Eu(3+) phosphors, which is attributed to the low crystal
field effect of the activator ions located in the highly distorted [LaO8]
polyhedra sites. The composition-optimized phosphors can find applications in
white light emitting diodes (LEDs).
PMID- 26442473
TI - Postexercise heart rate variability following treadmill and cycle exercise: a
comparison study.
AB - The purpose of this study was to compare postexercise heart rate variability
(HRV) immediately following acute bouts of treadmill (T) and cycle (C) exercise
at 65% of mode-specific maximal oxygen consumption reserve (65% VO2 R). Fourteen
apparently healthy men participated in this study. On two separate and randomized
days, each participant performed 30 min of exercise at 65% VO2 R on T and C.
Supine HRV was evaluated as normalized and log-transformed (ln) high-frequency
(HF) and low-frequency (LF) spectral power, as well as the LF:HF ratio in 5-min
segments immediately before (PRE) and at 10-15 min (POST1) and 25-30 min (POST2)
following each exercise bout. There were no significant differences in the HRV
values at PRE between the modalities. Following each exercise bout, lnHF was
significantly lower at POST2 following C compared to T. In addition, lnLF and
LF:HF were significantly higher at POST1 and POST2 following C compared to T. All
HRV metrics returned towards baseline 30 min following T but remained
significantly different than PRE values after C. These results suggest that
following exercise at 65% of mode-specific VO2 R, C is associated with a greater
delay of postexercise HRV recovery than T in apparently healthy men.
PMID- 26442474
TI - Identifying an optimal antiemetic regimen for patients receiving anthracycline
and cyclophosphamide-based chemotherapy for breast cancer--an inspection of the
evidence base informing clinical decision-making.
AB - BACKGROUND: Despite consensus recommendations for antiemetics in breast cancer
patients receiving anthracycline and cyclophosphamide-based chemotherapy, control
of chemotherapy-induced nausea and vomiting (CINV) remains sub-optimal.
OBJECTIVE: To inspect available evidence from randomized controlled trials (RCT)
in this population to establish treatment comparisons that have been studied,
outcomes that have been reported, and the extent of study heterogeneity. Review
of this data helps identify challenges for a systematic review comparing
antiemetic regimens, and to identify potential future trials. METHODS: A search
of Ovid MEDLINE(r), Embase and Cochrane CENTRAL was performed. We sought RCTs
comparing antiemetic regimens in breast cancer patients receiving anthracycline
and cyclophosphamide-based chemotherapy. We extracted information related to
study design, patient characteristics and interventions compared. Patterns of
outcome reporting were studied. While performing network meta-analysis was also
of interest, studies were judged highly heterogeneous and it was felt findings
from such work would be of uncertain validity. RESULTS: From 1062 citations, a
total of 30 full texts were retained. Overall, 47 antiemetic regimens were
evaluated using 15 different CINV endpoints. Treatment comparisons were diverse
and many were informed by single small trials. Reporting of key endpoints was
varied and all endpoints were not consistently available. Heterogeneity in
patients, chemotherapies administered, and intervention doses were noted.
CONCLUSIONS: Despite the availability of consensus recommendations for antiemetic
use, we identified challenges in synthesizing the evidence base including high
diversity in treatment comparisons, varied outcome reporting, and study
heterogeneity. These represent challenges to identifying an optimal antiemetic
regimen. Future antiemetic trials should incorporate more informed comparator
selection, report patient-oriented outcomes in a standard fashion, and provide
accessible data for these measures.
PMID- 26442475
TI - Mechanisms and latest clinical studies of new NK1 receptor antagonists for
chemotherapy-induced nausea and vomiting: Rolapitant and NEPA
(netupitant/palonosetron).
AB - Many patients undergoing moderately or highly emetogenic chemotherapy experience
chemotherapy-induced nausea/vomiting (CINV) and report reduced daily functioning,
despite prophylaxis with antiemetic drugs. While modern antiemetics have largely
alleviated acute emesis, management of nausea and delayed emesis remains
particularly challenging. We briefly review the pathophysiologic mechanisms of
CINV and the clinical impact of current antiemetics, i.e., the serotonin subtype
3 (5-HT3) receptor antagonists (RAs) and neurokinin-1 (NK1)RAs, before
summarizing recent data from clinical trials of new agents. The new antiemetics
reviewed include the two most recently approved drugs, the NK1RA rolapitant and
the fixed-dose combination product, NEPA, which is composed of the NK1RA
netupitant and the 5-HT3RA palonosetron. Phase 3 studies demonstrate improved
control of CINV in the delayed and overall phases when rolapitant is added to a
standard 5-HT3RA regimen. Phase 2 and phase 3 clinical trials with NEPA
demonstrate improved control of CINV in the acute, delayed, and overall phases
vs. 5-HT3RA regimens. These data suggest that delayed emesis can be substantially
reduced via combined 5-HT3 and NK1 receptor neurotransmitter pathway inhibition.
PMID- 26442476
TI - Lessons learned from two decades of research in nutrition education and obesity
prevention: Considerations for alcohol education.
AB - OBJECTIVE: Effective health interventions involve an understanding of the
specific needs and wants of the population to be served. Lessons from more than
two decades of obesity prevention can be applied to understanding how to design
and implement other behaviorally-focused health interventions, including those
for alcohol education. METHODS: Three obesity prevention campaigns were reviewed
and evaluated for elements critical to their success in achieving desired
outcomes. RESULTS: Evaluation of the three cases studies revealed six key
elements common to successful interventions. These include: specifying the
desired outcome at the outset, understanding the target population, identifying a
framework for the intervention, creating a campaign "identity", enlisting
champions, and evaluating both outcomes and process. CONCLUSION: Successful
health interventions should be behaviorally-focused and include multiple
components to address the various factors that influence behavior. A clear
understanding of how and why desired outcomes were achieved can inform
dissemination to a wider audience and improve sustainability. PRACTICE
IMPLICATIONS: Lessons learned from obesity prevention provide guidance for
development of alcohol education. It must be acknowledged that there is still
much to be learned to maximize success in prevention efforts. It is likely that
analysis of future efforts in alcohol education can contribute to that
understanding.
PMID- 26442477
TI - Swollen and tender left nipple.
PMID- 26442478
TI - Anthelmintic efficacy of cinnamaldehyde and cinnamic acid from cortex cinnamon
essential oil against Dactylogyrus intermedius.
AB - Utilization of chemical pesticide to control monogenean diseases is often
restricted in many countries due to the development of pesticide resistance and
concerns of chemical residues and environmental contamination. Thus, the use of
antiparasitic agents from plants has been explored as a possible way for
controlling monogenean infections. Extracts from Cinnamomum cassia were
investigated under in vivo conditions against Dactylogyrus intermedius in
goldfish. The two bioactive compounds, cinnamaldehyde and cinnamic acid, were
identified using nuclear magnetic resonance and electrospray ionization mass
spectrometry. The 48 h median effective concentrations (EC(50)) for these
compounds against D. intermedius were 0.57 and 6.32 mg L(-1), respectively. The
LD(50) of cinnamaldehyde and cinnamic acid were 13.34 and 59.66 mg L(-1) to
goldfish in 48 h acute toxicity tests, respectively. These data confirm that
cinnamaldehyde is effective against D. intermedius, and the cinnamaldehyde
exhibits potential for the development of a candidate antiparasitic agent.
PMID- 26442480
TI - Hydrogenation of Pt/TiO2{101} nanobelts: a driving force for the improvement of
methanol catalysis.
AB - Single-crystalline anatase TiO2 nanobelts with a dominant surface of the {101}
facet were hydrogenated and used as substrates of platinum for methanol oxidation
reaction (MOR). The hydrogenated TiO2 anatase{101} supporting Pt exhibits a 228%
increase of current density for methanol oxidation compared with the same system
without hydrogenation under dark conditions. The synergetic interactions of
hydrogenated anatase{101} with the Pt cluster were investigated through first
principles calculations, and found that the hydrogenation shifts the conduction
band minimum to the Fermi level of pristine TiO2, and reduces the activation
barrier for methanol dissociation considerably. Thus, this work provides an
experimental and theoretical basis for developing non-carbon substrates with high
electro-catalytic activity toward MOR.
PMID- 26442479
TI - System N transporters are critical for glutamine release and modulate metabolic
fluxes of glucose and acetate in cultured cortical astrocytes: changes induced by
ammonia.
AB - Glutamine (Gln) is synthesized in astrocytes from glutamate (Glu) and ammonia,
whereupon it can be released to be transferred to neurons. This study evaluated
the as yet not definitely established role of the astrocytic Gln transporters SN1
and SN2 (Slc38a3 and Slc38a5 respectively) in Gln release and metabolic fluxes of
glucose and acetate, the canonical precursors of Glu. Cultured neocortical
astrocytes were grown in the absence or presence of ammonia (5 mM NH4 Cl, 24 h),
which deregulates astrocytic metabolism in hyperammonemic encephalopathies. HPLC
analyses of cell extracts of SN1/SN2 siRNA-treated (SN1/SN2-) astrocytes revealed
a ~ 3.5-fold increase in Gln content and doubling of glutathione, aspartate,
alanine and glutamate contents, as compared to SN1/SN2+ astrocytes. Uptake and
efflux of preloaded [(3) H]Gln was likewise significantly decreased in SN1/SN2-
astrocytes. The atom percent excess (13) C values (given as M + 1) for alanine,
aspartate and glutamate were decreased when the SN1/SN2- cells were incubated
with [1-(13) C] glucose, while Gln consumption was not changed. No difference was
seen in M + 1 values in SN1/SN2- cells incubated with [2-(13) C] acetate, which
were not treated with ammonia. In SN1/SN2- astrocytes, the increase in Gln
content and the decrease in radiolabeled Gln release upon exposure to ammonia
were found abrogated, and glutamate labeling from [2-(13) C]acetate was decreased
as compared to SN1/SN2+ astrocytes. The results underscore a profound role of SN1
and/or SN2 in Gln release from astrocytes under physiological conditions, but
less so in ammonia-overexposed astrocytes, and appear to manifest dependence of
astrocytic glucose metabolism to Glu/Gln on unimpaired SN1/SN2- mediated Gln
release from astrocytes. The astrocytic N system transporters SN1 and SN2 show
preponderance to mediate glutamine (Gln) efflux. Under hyperammonemic conditions,
accumulation of Gln, a direct product of ammonia detoxification, may deregulate
astrocytic metabolism and seems to be responsible for astrocytic swelling. This
study evaluated not definitely established role of SN1 and SN2 in Gln release and
metabolic fluxes of radiolabeled glucose and acetate. Simultaneous silencing of
SN1/SN2 transporters increase Gln, glutathione, aspartate, alanine and glutamate
contents (Panel B; marked in red) as compare to non-silenced astrocytes (Panel
A). The atom percent excess (13) C values (given as M + 1) for alanine, aspartate
and glutamate were decreased when the cells with silenced transporters were
incubated with [1-(13) C]glucose, whereas no difference was seen in M + 1 values
when those cells were incubated with [2-(13) C]acetate. Ammonia abrogated the
increase in Gln content and decrease in radiolabeled Gln release in astrocytes
with silenced transporters, but caused a decrease in glutamate labeling from [2
(13) C]acetate.
PMID- 26442481
TI - Where do all the red blood cells (RBCs) go? Results of a survey of RBC use in
England and North Wales in 2014.
AB - BACKGROUND: Knowledge of blood utilization can assist clinicians in directing
patient blood management (PBM) initiatives and can facilitate demand planning by
blood services. We describe a national study of red blood cell (RBC) utilization
in England and North Wales in 2014. STUDY DESIGN AND METHODS: All hospitals that
are supplied with blood components by NHS Blood and Transplant (NHSBT) were asked
to provide data on the age and sex of all recipients of transfusions of RBCs, and
the clinical indication for every unit transfused, for two separate weeks in
2014. Clinical indication categories were derived from those used in previous
studies in an English region. Completeness of data collection was checked against
NHSBT issue and wastage data. RESULTS: Data on 46,111 RBC units were collected,
representing 73% of all RBCs issued by NHSBT during the weeks surveyed. A total
of 67% of RBC units were transfused for a medical indication, with 27 and 6%
being transfused for surgical and obstetric/gynecologic indications,
respectively. For comparison, figures from a study in the North of England in
2009, on which this national study was based, showed that 64% of RBCs were
transfused to medical patients. All but 20 units could be ascribed to a broad
clinical heading, for example, "gastrointestinal bleeding." CONCLUSION: Our
findings confirm the previous regional finding that the percentage of RBC units
that are transfused to surgical patients in England and North Wales is now much
lower than for medical patients and suggest that PBM initiatives should now focus
on medical patients.
PMID- 26442482
TI - Beta diversity as a tool for determining priority streams for management actions.
AB - Beta diversity has become essential for understanding ecosystem functioning and
for determining biodiversity-conservation priority areas. However, the beta
diversity patterns of invertebrates in tropical aquatic ecosystems are not well
known, particularly in streams. Using data from low-order streams located in
southern Brazil, we evaluated the beta diversity of Chironomidae. We tested the
hypothesis that increased environmental heterogeneity increases beta diversity.
The streams were grouped into two categories, rural and urban, according to the
percentage of urbanization in their micro-basins. Our results showed that the
heterogeneity of environmental variables can determine the beta diversity of
Chironomidae, and the increased environmental heterogeneity caused by differences
in the intensity of urbanization impacts can increase the beta diversity in urban
streams. Therefore, the intensified impacts of anthropogenic activities in
aquatic ecosystems can also increase beta diversity. Finally, we suggested that
beta diversity can be an effective tool for not only designing measures and
determining priority conservation areas, but also accurately identifying
potentially degraded and priority sites that require water management plans.
PMID- 26442483
TI - About the interest of a zooplankton compartment in pond systems: methodology to
study the growth kinetic of Daphnia pulex on Scenedesmus sp.
AB - A reliable characterization of cladocerans' growth kinetic on their substrates is
crucial for the estimation of their biochemical conversion rate in pond models.
Although many studies reported cladocerans' growth inhibitions by high
chlorophyceae contents, their growth kinetics had continued to be described in
many pond system models by Monod-type kinetic, which describes growth saturation
by high substrate contents, but fails to explain the disappearance of cladocerans
observed during chlorophyceae's bloom periods. This study aimed to develop a
methodology and assess whether growth-inhibition-type models used to describe
microbial growth kinetics can be applicable to cladocerans. Experiments were
carried out using Daphnia pulex populations and Scenedesmus sp. First, biomass of
D. pulex was measured through digital image processing (DIP) during growth
experiments. Then, three candidate models (i.e., Andrews, Edward and Haldane
models), along with the Monod model, were fitted to the observed data and
compared. The results showed that the DIP technique provided reliable results for
estimating the biomass of D. pulex. Our findings show that the candidate growth
inhibition-type models satisfactorily described D. pulex's growth kinetic (86%
variance accounted for). Scenesdemus sp. were not strong inhibitors of the growth
of D. pulex (high inhibition constant and low half-saturation constant found).
PMID- 26442484
TI - Use of multivariate calibration models based on UV-Vis spectra for seawater
quality monitoring in Tianjin Bohai Bay, China.
AB - A series of ultraviolet-visible (UV-Vis) spectra from seawater samples collected
from sites along the coastline of Tianjin Bohai Bay in China were subjected to
multivariate partial least squares (PLS) regression analysis. Calibration models
were developed for monitoring chemical oxygen demand (COD) and concentrations of
total organic carbon (TOC). Three different PLS models were developed using the
spectra from raw samples (Model-1), diluted samples (Model-2), and diluted and
raw samples combined (Model-3). Experimental results showed that: (i) possible
nonlinearities in the signal concentration relationships were well accounted for
by the multivariate PLS model; (ii) the predicted values of COD and TOC fit the
analytical values well; the high correlation coefficients and small root mean
squared error of cross-validation (RMSECV) showed that this method can be used
for seawater quality monitoring; and (iii) compared with Model-1 and Model-2,
Model-3 had the highest coefficient of determination (R2) and the lowest number
of latent variables. This latter finding suggests that only large data sets that
include data representing different combinations of conditions (i.e., various
seawater matrices) will produce stable site-specific regressions. The results of
this study illustrate the effectiveness of the proposed method and its potential
for use as a seawater quality monitoring technique.
PMID- 26442485
TI - Summertime conditions of a muddy estuarine environment: the EsCoSed project
contribution.
AB - As part of the Estuarine Cohesive Sediments (EsCoSed) project, a field experiment
was performed in a highly engineered environment, acting as a natural laboratory,
to study the physico-chemical properties of estuarine sediments and the
associated hydro-morphodynamics during different seasons. The present
contribution focuses on the results obtained from the summertime monitoring of
the most downstream part of the Misa River (Senigallia, Italy). The measured
hydrodynamics suggested a strong interaction between river current, wave forcing
and tidal motion; flow velocities, affected by wind waves traveling upstream,
changed significantly along the water column in both direction and magnitude.
Surficial salinities in the estuary were low in the upper reaches of the estuary
and exceeded 10 psu before the river mouth. Montmorillonite dominated the clay
mineral assemblage, suggesting that large, low density flocs with high settling
velocities (>1 mm s(-1)) may dominate the suspended aggregate materials.
PMID- 26442486
TI - Leaching behavior of total organic carbon, nitrogen, and phosphorus from banana
peel.
AB - The leaching behavior of organic carbon and nutrient compounds from banana peel
(BP) was investigated in batch assays with respect to particle size, contact
time, pH value, and temperature. The granularity, contact time, pH, and
temperature caused no significant effects on the leaching of total phosphorus
(TP) from the BP. The maximum leached total nitrogen (TN) content was found at pH
5.0 and 90 minutes, while no significant effects were caused by the granularity
and temperature. The maximum leached total organic carbon (TOC) content was found
by using a powder of 40 mesh, 150 minutes and at pH 6.0, while the temperature
had no effect on the TOC leaching. The proportions of the TN, TP, and TOC
contents leached from the dried BP ranged from 33.6% to 40.9%, 60.4% to 72.7%,
and 8.2% to 9.9%, respectively, indicating that BP could be a potential pollution
source for surface and ground water if discharged as domestic waste or reutilized
without pretreatment.
PMID- 26442487
TI - An ecological compensation standard based on emergy theory for the Xiao Honghe
River Basin.
AB - The calculation of an ecological compensation standard is an important, but also
difficult aspect of current ecological compensation research. In this paper, the
factors affecting the ecological-economic system in the Xiao Honghe River Basin,
China, including the flow of energy, materials, and money, were calculated using
the emergy analysis method. A consideration of the relationships between the
ecological-economic value of water resources and ecological compensation allowed
the ecological-economic value to be calculated. On this basis, the amount of
water needed for dilution was used to develop a calculation model for the
ecological compensation standard of the basin. Using the Xiao Honghe River Basin
as an example, the value of water resources and the ecological compensation
standard were calculated using this model according to the emission levels of the
main pollutant in the basin, chemical oxygen demand. The compensation standards
calculated for the research areas in Xipin, Shangcai, Pingyu, and Xincai were
34.91 yuan/m3, 32.97 yuan/m3, 35.99 yuan/m3, and 34.70 yuan/m3, respectively, and
such research output would help to generate and support new approaches to the
long-term ecological protection of the basin and improvement of the ecological
compensation system.
PMID- 26442488
TI - Assessment of flood hazard in a combined sewer system in Reykjavik city centre.
AB - Short-duration precipitation bursts can cause substantial property damage and
pose operational risks for wastewater managers. The objective of this study was
to assess the present and possible future flood hazard in the combined sewer
system in Reykjavik city centre. The catchment is characterised by two hills
separated by a plain. A large portion of the pipes in the aging network are
smaller than the current minimum diameter of 250 mm. Runoff and sewer flows were
modelled using the MIKE URBAN software package incorporating both historical
precipitation and synthetic storms derived from annual maximum rainfall data.
Results suggest that 3% of public network manholes were vulnerable to flooding
during an 11-year long rainfall sequence. A Chicago Design Storm (CDS)
incorporating a 10-minute rainfall burst with a 5-year return period predicted
twice as many flooded manholes at similar locations. A 20% increase in CDS
intensity increased the number of flooded manholes and surface flood volume by
70% and 80%, respectively. The flood volume tripled if rainfall increase were
combined with urban re-development, leading to a 20% increase in the runoff
coefficient. Results highlight the need for reducing network vulnerabilities,
which include decreased pipe diameters and low or drastically varying pipe
grades.
PMID- 26442489
TI - Oxidative decomposition properties of cationic exchange resins producing SO4(2-)
in power plants.
AB - The sulphate content of a system increases when strong-acid cationic exchange
resins leak into a system or when sulphonic acid groups on the resin organic
chain detach. To solve this problem, a dynamic cycle method was used in
dissolution experiments of several resins under H2O2 or residual chlorine
conditions. Results show that after performing dynamic cycle experiments for 120
hours under oxidizing environments, the SO4(2-) and total organic carbon (TOC)
released by four kinds of resins increased with time, contrary to their release
velocity. The quantity of released SO4(2-) increased as the oxidizing ability of
oxidants was enhanced. Results showed that the quantity and velocity of released
SO4(2-) under residual chlorine condition were larger than those under H2O2
condition. Data analysis of SO4(2-) and TOC released from the four kinds of
resins by the dynamic cycle experiment revealed that the strength of oxidation
resistance of the four resins were as follows: 650C>1500H>S200>SP112H.
PMID- 26442490
TI - Assessment of LID practices for restoring pre-development runoff regime in an
urbanized catchment in southern Finland.
AB - This study quantifies the effects of common stormwater management techniques on
urban runoff generation. Simulated flow rates for different low impact
development (LID) scenarios were compared with observed flow rates during
different urban construction phases in a catchment (12.3 ha) that was developed
from natural forest to a residential area over a monitoring period of 5 years.
The Storm Water Management Model (SWMM) was calibrated and validated against the
observed flow rates in the fully developed catchment conditions, and it was then
applied to parameterize the LID measures and produce scenarios of their
hydrological impacts. The results from the LID scenarios were compared with the
observed flow rates in the pre-development and the partially developed catchment
conditions. The results show that LID controls reduce urban runoff towards the
flow conditions in the partially developed catchment, but the reduction effect
diminishes during large rainfall events. The hydrographs with LID are still
clearly different from the observed pre-development levels. Although the full
restoration of pre-development flow conditions was not feasible, a combination of
several measures controlling both volumes and retention times of storm runoff
appeared to be effective for managing the stormwater runoff and mitigating the
negative impacts of urban development.
PMID- 26442491
TI - Use of geological mapping tools to improve the hydraulic performance of SuDS.
AB - Most cities in Denmark are situated on low permeable clay rich deposits. These
sediments are of glacial origin and range among the most heterogeneous, with
hydraulic conductivities spanning several orders of magnitude. This heterogeneity
has obvious consequences for the sizing of sustainable urban drainage systems
(SuDS). We have tested methods to reveal geological heterogeneity at field scale
to identify the most suitable sites for the placement of infiltration elements
and to minimize their required size. We assessed the geological heterogeneity of
a clay till plain in Eastern Jutland, Denmark measuring the shallow subsurface
resistivity with a geoelectrical multi-electrode system. To confirm the
resistivity data we conducted a spear auger mapping. The exposed sediments ranged
from clay tills over sandy clay tills to sandy tills and correspond well to the
geoelectrical data. To verify the value of geological information for placement
of infiltration elements we carried out a number of infiltration tests on
geologically different areas across the field, and we observed infiltration rates
two times higher in the sandy till area than in the clay till area, thus
demonstrating that the hydraulic performance of SuDS can be increased
considerably and oversizing avoided if field geological heterogeneity is revealed
before placing SuDS.
PMID- 26442492
TI - Understanding the contribution of biofilm in an integrated fixed-film-activated
sludge system (IFAS) designed for nitrogen removal.
AB - The objective of this study is to improve knowledge on the integrated fixed-film
activated sludge (IFAS) system designed for nitrogen removal. Biofilm growth and
its contribution to nitrification were monitored under various operating
conditions in a semi-industrial pilot-scale plant. Nitrification rates were
observed in biofilms developed on free-floating media and in activated sludge
operated under a low sludge retention time (4 days) and at an ammonia loading
rate of 45-70 gNH4-N/kgMLVSS/d. Operational conditions, i.e. oxygen
concentration, redox potential, suspended solids concentration, ammonium and
nitrates, were monitored continuously in the reactors. High removal efficiencies
were observed for carbon and ammonium at high-loading rate. The contribution of
biofilm to nitrification was determined as 40-70% of total NOx-N production under
the operating conditions tested. Optimal conditions to optimize process compacity
were determined. The tested configuration responds especially well to winter and
summer nitrification conditions. These results help provide a deeper
understanding of how autotrophic biomass evolves through environmental and
operational conditions in IFAS systems.
PMID- 26442493
TI - Research on classified real-time flood forecasting framework based on K-means
cluster and rough set.
AB - This research presents a new classified real-time flood forecasting framework. In
this framework, historical floods are classified by a K-means cluster according
to the spatial and temporal distribution of precipitation, the time variance of
precipitation intensity and other hydrological factors. Based on the classified
results, a rough set is used to extract the identification rules for real-time
flood forecasting. Then, the parameters of different categories within the
conceptual hydrological model are calibrated using a genetic algorithm. In real
time forecasting, the corresponding category of parameters is selected for flood
forecasting according to the obtained flood information. This research tests the
new classified framework on Guanyinge Reservoir and compares the framework with
the traditional flood forecasting method. It finds that the performance of the
new classified framework is significantly better in terms of accuracy.
Furthermore, the framework can be considered in a catchment with fewer historical
floods.
PMID- 26442494
TI - French vertical-flow constructed wetland design: adaptations for tropical
climates.
AB - The French Outermost Regions are under tropical climate yet still have to comply
with both French and EU regulations. French vertical-flow constructed wetland
systems appear well adapted to the technical specifics of these regions but their
adaptation to tropical climate requires new design guidelines to be defined (area
needed, number of filters, type of plants, material to be used, etc.). A study
was started in 2008, with backing from the national water authorities, to
implement full-scale experimental sites and assess the impacts of local context
on design and performances. This paper reports the monitoring results on three
vertical-flow constructed wetlands fed directly with raw wastewater (known as the
'French system') in Mayotte and French Guiana. The plants, now in operation for
between 1 and 6 years, range from 160 to 480 population equivalent (p.e.).
Monitoring consisted of 28 daily composite flow samples in different seasons (dry
season, rainy season) at the inlet and outlet of each filter. Performances are
benchmarked against French mainland area standards from Irstea's database.
Results show that performances are improved by warmer temperature for chemical
oxygen demand (COD), suspended solids (SS) and total Kjeldahl nitrogen (TKN) and
satisfy national quality objectives with a single stage of filters. Treatment
plant footprint can thus be reduced as only two parallel filters are needed.
Indeed, warm temperatures allow faster mineralization of the sludge deposit,
making it possible to operate at similar rest and feeding period durations.
Systems operated using one twin-filter stage can achieve over 90% COD, SS and TKN
removal for a total surface of 0.8 m2/p.e.
PMID- 26442495
TI - Impact on sludge inventory and control strategies using the benchmark simulation
model no. 1 with the Burger-Diehl settler model.
AB - An improved one-dimensional (1-D) model for the secondary clarifier, i.e. the
Burger-Diehl model, was recently presented. The decisive difference to
traditional layer models is that every detail of the implementation is in
accordance with the theory of partial differential equations. The Burger-Diehl
model allows accounting for hindered and compressive settling as well as inlet
dispersion. In this contribution, the impact of specific features of the Burger
Diehl model on settler underflow concentration predictions, plant sludge
inventory and mixed liquor suspended solids based control actions are
investigated by using the benchmark simulation model no. 1. The numerical results
show that the Burger-Diehl model allows for more realistic predictions of the
underflow sludge concentration, which is essential for more accurate wet weather
modelling and sludge waste predictions. The choice of secondary settler model
clearly has a profound impact on the operation and control of the entire
treatment plant and it is recommended to use the Burger-Diehl model as of now in
any wastewater treatment plant modelling effort.
PMID- 26442496
TI - An investigation into the effectiveness of sand media amended with biochar to
remove BOD5, suspended solids and coliforms using wetland mesocosms.
AB - Constructed wetland ecotechnologies (CWEs) are a promising solution to
effectively treat domestic wastewater in developing countries at low cost. This
paper reports the findings of the effectiveness of sand media amended with woody
biochar and two plants species (Melaleuca quinquenervia and Cymbopogon citratus)
in removing biological oxygen demand (BOD5), suspended solids and coliforms. The
experimental design consisted of 21 vertical flow (VF) mesocosms. There were
seven media treatments using sand amended with varying proportions of biochar.
During the first 8 months, the mesocosms were loaded with secondary clarified
wastewater (SCW) then septage. The influent had a 4-day hydraulic retention time.
Samples were monitored for BOD5, total suspended solids (TSS), total volatile
solids (TVS), total coliforms and faecal coliforms. In the first 8 months, there
were no significant performance differences between media treatments in the
outflow concentrations of BOD5, TSS and TVS. The significant differences occurred
during the last 3 months; using septage with biochar additions performed better
than pure sand. For coliforms, the significant differences occurred after 6
months. In conclusion, the addition of biochar was not effective for SCW. The VF
mesocosms system proved to be more effective in removing BOD5, TSS, TVS and
coliforms when septage was loaded into the media.
PMID- 26442497
TI - Preparation of cationic starch microspheres and study on their absorption to
anionic-type substance.
AB - Cationic starch microspheres (CSMs) were prepared from lab-made neutral starch
based microspheres using a cationic adsorbent, namely 3-chloro-2
hydroxypropyltrimethyl ammonium chloride, as the cationic etherifying agent.
Detection by scanning electron microscopy, Fourier transform infrared
spectroscopy (FTIR), and laser diffraction techniques revealed that CSMs had
coarse surfaces with good sphericity and dispersibility. Differential thermal
analysis showed the lower thermostability of the CSMs' main chains. Furthermore,
scores of experiments confirmed that CSMs are capable of absorption to N
(phosphonomethyl) iminodiacetic acid (PMIDA), a type of anionic substance, which
is the intermediate to the preparation of glyphosate, maximally up to 95.24 mg/g.
Compared with the Freundlich isotherm model, the Langmuir isotherm model can
better describe the absorption process. The kinetic study showed that the pseudo
second-order model demonstrated a better correlation of the experimental data in
contrast with the pseudo-first-order model. It can be therefore concluded that
the rate-limiting step was the chemical absorption rather than the mass
transport.
PMID- 26442498
TI - Novel diesel-oil-degrading bacteria and fungi from the Ecuadorian Amazon
rainforest.
AB - Isolating new diesel-oil-degrading microorganisms from crude-oil contaminated
sites and evaluating their degradation capacities are vitally important in the
remediation of oil-polluted environments and crude-oil exploitation. In this
research, new hydrocarbon-degrading bacteria and fungi were isolated from the
crude-oil contaminated soil of the oil-fields in the Amazon rainforest of north
east Ecuador by using a soil enrichment technique. Degradation analysis was
tracked by gas chromatography and a flame ionization detector. Under laboratory
conditions, maximum degradability of the total n-alkanes reached up to 77.34 and
62.62 removal ratios after 30 days of incubation for the evaporated diesel oil by
fungi (isolate-1) and bacteria (isolate-1), respectively. The 16S/18S rDNA
sequence analysis indicated that the microorganisms were most closely (99-100%)
related to Bacillus cereus (isolate-1), Bacillus thuringiensis (isolate-2),
Geomyces pannorum (isolate-1), and Geomyces sp. (isolate-2). Therefore, these
strains enable the degradation of hydrocarbons as the sole carbon source, and
these findings will benefit these strains in the remediation of oil-polluted
environments and oil exploitation.
PMID- 26442499
TI - Water-saving analysis on an effective water reuse system in biodiesel feedstock
production based on Chlorella zofingiensis fed-batch cultivation.
AB - The micralgae-based biofuel obtained from dairy wastewater (DWW) is considered a
promising source of energy. However, this process consumes water due to the
concentration of wastewater being normally too high for some micoralgae
cultivation, and dilution is always needed. In this work, the cultivation of
microalgae has been examined in non-recirculated water (NR) and recirculated
water systems (R). The growth of Chlorella zofingiensis and the nutrient removal
of DWW have been recorded. The comparison indicates the R had a little more
advantage in biomass and lipid output (1.55, 0.22 g, respectively) than the NR
(1.51, 0.20 g, respectively). However, the total chemical oxygen demand (COD),
total Kjeldahl nitrogen (TKN), and total phosphorus (TP) removals of the R were
lower than those of the NR system during the culture. The highest removal of
total COD, TKN, and TP were 85.05%, 93.64%, and 98.45%, respectively.
Furthermore, no significant difference has been observed in the higher heating
value and lipid content of the biomass of the R and NR. The results show the R
can save 30% of the total water input during the culture. All above results
indicate the R system has great potential in industry.
PMID- 26442500
TI - Electrochemical degradation of perfluoroalkyl and polyfluoroalkyl substances
(PFASs) in groundwater.
AB - Perfluoroalkyl and polyfluoroalkyl substances (PFASs) represent hazardous
pollutants and are frequently detected in the environment, e.g. in contaminated
groundwater. PFASs are persistent to biodegradation and conventional oxidation
processes such as ozonation. In this study electrochemical degradation of PFASs
on boron-doped diamond (BDD) electrodes is demonstrated. Experiments were
performed with model solutions and contaminated groundwater with a dissolved
organic carbon (DOC) content of 13 mg/L. The perfluorinated carboxylic acids
(PFCAs) perfluorobutanoate, perfluoropentanoate, perfluorohexanoate,
perfluoroheptanoate and perfluorooctanoate, and the perfluorinated sulfonic acids
(PFSAs) perfluorobutane sulfonate, perfluorohexane sulfonate, perfluorooctane
sulfonate and 6:2 fluorotelomer sulfonate were detected in the groundwater
samples. At PFAS concentrations ranging from 0.26 to 34 mg/L (0.7 to 79 MUM), the
degradation of PFASs was achieved despite of the high DOC background. Pseudo
first-order kinetic constants of PFSA degradation increased with the increase of
carbon chain length. Fluoride formation as well as the generation of PFCAs with
shortened chain lengths was observed. Inorganic byproducts such as perchlorate
were also formed and have to be considered in further process optimization.
PMID- 26442501
TI - Improved light-transmission method for the study of LNAPL migration and
distribution rule.
AB - In this study, diesel was selected as a pollutant to study the migration and
distribution rule of light non-aqueous phase liquid (LNAPL) in the simulated
vadose zone. Saturation was regarded as a critical parameter to reflect the LNAPL
migration and distribution rule. To get LNAPL saturation distribution figures, an
image processing method of saturation was established to improve light
transmission technology, which can deal with digital camera images. Results
showed that the vadose zone contains three areas from top to bottom, named dry
media, transition zone and capillary zone. The system has two interfaces at which
moisture content increased significantly. The significant increase in moisture
content induced two apparent horizontal LNAPL diffusions in the two interfaces.
Furthermore, the highly saturated LNAPL was mostly distributed near the wet
interface, which lay between the dry media and the transition zone. Moreover, the
downstream expansion of LNAPL in the capillary zone was promoted by groundwater
flow, yet cutting off LNAPL supply could stop the downstream expansion after a
period of time. The accuracy of this image processing method of saturation was
verified by mass balance theory and reported a relative error of 4.38%.
PMID- 26442502
TI - Kupffer's vesicle size threshold for robust left-right patterning of the
zebrafish embryo.
AB - BACKGROUND: Motile cilia in the "organ of asymmetry" create directional fluid
flows that are vital for left-right (LR) asymmetric patterning of vertebrate
embryos. Organ function often depends on tightly regulated organ size control,
but the role of organ of asymmetry size in LR patterning has remained unknown.
Observations of the organ of asymmetry in the zebrafish, called Kupffer's vesicle
(KV), have suggested significant variations in KV size in wild-type embryos,
raising questions about the impact of KV organ size on LR patterning. RESULTS: To
understand the relationship between organ of asymmetry size and its function, we
characterized variations in KV at several developmental stages and in several
different zebrafish strains. We found that the number of KV cilia and the size of
the KV lumen were highly variable, whereas the length of KV cilia showed less
variation. These variabilities were similar among different genetic backgrounds.
By specifically modulating KV size and analyzing individual embryos, we
identified a size threshold that is necessary for KV function. CONCLUSIONS:
Together these results indicate the KV organ of asymmetry size is not tightly
controlled during development, but rather must only exceed a threshold to direct
robust LR patterning of the zebrafish embryo.
PMID- 26442503
TI - Building a cognitive map by assembling multiple path integration systems.
AB - Path integration and cognitive mapping are two of the most important mechanisms
for navigation. Path integration is a primitive navigation system which computes
a homing vector based on an animal's self-motion estimation, while cognitive map
is an advanced spatial representation containing richer spatial information about
the environment that is persistent and can be used to guide flexible navigation
to multiple locations. Most theories of navigation conceptualize them as two
distinctive, independent mechanisms, although the path integration system may
provide useful information for the integration of cognitive maps. This paper
demonstrates a fundamentally different scenario, where a cognitive map is
constructed in three simple steps by assembling multiple path integrators and
extending their basic features. The fact that a collection of path integration
systems can be turned into a cognitive map suggests the possibility that
cognitive maps may have evolved directly from the path integration system.
PMID- 26442504
TI - A Novel Public Library-Based Sexually Transmitted Infection Screening Program for
Younger High-Risk Groups in Omaha, Nebraska, USA.
AB - Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the two most
commonly reported sexually transmitted infections (STIs) in the United States
(U.S.) and Douglas County, Nebraska has STI rates consistently above the U.S.
average. The Douglas County Health Department (DCHD) developed an outreach CT and
NG screening program in public libraries to address the problem beyond the
traditional STI clinic setting. This study evaluates the effectiveness of the
program and identifies factors predictive of CT and NG infections. A
retrospective review of surveys of library patrons and DCHD traditional STI
clinic clients who submitted urine tests for CT and NG from June 2010 through
April 2014 was done. Chi square, Fisher exact, Student's t tests, univariate and
multivariate logistic regression were conducted. A total of 977 library records
and 4871 DCHD clinic records were reviewed. The percent positive was lower in the
library than in the traditional clinic for CT (9.9 vs. 11.2 %) and NG (2.74 vs.
5.3 %) (p = 0.039 and p < 0.001, respectively). Library clients were more likely
to be 19 years and younger (OR 6.14, 95 % CI: 5.0, 7.5), Black (OR 3.4, 95 % CI:
2.8, 4.1), and asymptomatic (OR 12.4, 95 % CI: 9.9, 15.5) compared to traditional
clinic clients. The library STI screening program effectively reaches a younger,
asymptomatic, and predominantly Black population compared to a traditional health
department clinic site.
PMID- 26442505
TI - Escherichia coli and the Emergence of Molecular Biology.
AB - The creation of the "Phage group" by M. Delbruck, S. E. Luria, and A. D. Hershey
in 1940 at Cold Spring Harbor played a crucial role in the development of
molecular biology. In the 1940s, working with Escherichia coli and its viruses,
Luria and Delbruck discovered the spontaneous nature of bacterial mutations and
Hershey described recombination in bacteriophages and demonstrated with M. Chase
that the genetic material that infects bacteria is DNA. At the same time, S.
Benzer defined the structure of a functional genetic unit and J. Lederberg and E.
Tatum discovered sexual recombination between bacteria. Some years later,
Lederberg's group discovered extrachromosomal particles, the plasmids, and a
novel way of genetic transfer through bacteriophages, called transduction. In
1949, at the Pasteur Institute in Paris, A. Lwoff uncovered the mechanism of
lysogeny. Shortly afterwards, F. Jacob and E. Wollman unraveled the mechanism of
the sexual process in E. coli and established the circularity of the bacterial
chromosome. In the 1960s, J. Monod and F. Jacob, by genetic analysis of the E.
coli lactose system, proposed the operon model for gene regulation and introduced
the concept of messenger RNA. The elucidation of the double helix structure of
DNA in 1953 by F. Crick and J. Watson had major consequences: the establishment
of the copying mechanism (Meselson and Stahl), the discovery of the nature of the
genetic code (S. Brenner) leading to its deciphering. E. coli and its phages were
instrumental in the development of recombinant DNA technology based on the
discovery of the restriction-modification system by W. Arber.
PMID- 26442507
TI - Stationary-Phase Gene Regulation in Escherichia coli S.
AB - In their stressful natural environments, bacteria often are in stationary phase
and use their limited resources for maintenance and stress survival. Underlying
this activity is the general stress response, which in Escherichia coli depends
on the sigmaS (RpoS) subunit of RNA polymerase. sigmaS is closely related to the
vegetative sigma factor sigma70 (RpoD), and these two sigmas recognize similar
but not identical promoter sequences. During the postexponential phase and entry
into stationary phase, sigmaS is induced by a fine-tuned combination of
transcriptional, translational, and proteolytic control. In addition, regulatory
"short-cuts" to high cellular sigmaS levels, which mainly rely on the rapid
inhibition of sigmaS proteolysis, are triggered by sudden starvation for various
nutrients and other stressful shift conditons. sigmaS directly or indirectly
activates more than 500 genes. Additional signal input is integrated by sigmaS
cooperating with various transcription factors in complex cascades and
feedforward loops. Target gene products have stress-protective functions,
redirect metabolism, affect cell envelope and cell shape, are involved in biofilm
formation or pathogenesis, or can increased stationary phase and stress-induced
mutagenesis. This review summarizes these diverse functions and the amazingly
complex regulation of sigmaS. At the molecular level, these processes are
integrated with the partitioning of global transcription space by sigma factor
competition for RNA polymerase core enzyme and signaling by nucleotide second
messengers that include cAMP, (p)ppGpp, and c-di-GMP. Physiologically, sigmaS is
the key player in choosing between a lifestyle associated with postexponential
growth based on nutrient scavenging and motility and a lifestyle focused on
maintenance, strong stress resistance, and increased adhesiveness. Finally,
research with other proteobacteria is beginning to reveal how evolution has
further adapted function and regulation of sigmaS to specific environmental
niches.
PMID- 26442506
TI - Homologous Recombination-Experimental Systems, Analysis, and Significance.
AB - Homologous recombination is the most complex of all recombination events that
shape genomes and produce material for evolution. Homologous recombination events
are exchanges between DNA molecules in the lengthy regions of shared identity,
catalyzed by a group of dedicated enzymes. There is a variety of experimental
systems in Escherichia coli and Salmonella to detect homologous recombination
events of several different kinds. Genetic analysis of homologous recombination
reveals three separate phases of this process: pre-synapsis (the early phase),
synapsis (homologous strand exchange), and post-synapsis (the late phase). In E.
coli, there are at least two independent pathway of the early phase and at least
two independent pathways of the late phase. All this complexity is incongruent
with the originally ascribed role of homologous recombination as accelerator of
genome evolution: there is simply not enough duplication and repetition in
enterobacterial genomes for homologous recombination to have a detectable
evolutionary role and therefore not enough selection to maintain such a
complexity. At the same time, the mechanisms of homologous recombination are
uniquely suited for repair of complex DNA lesions called chromosomal lesions. In
fact, the two major classes of chromosomal lesions are recognized and processed
by the two individual pathways at the early phase of homologous recombination. It
follows, therefore, that homologous recombination events are occasional
reflections of the continual recombinational repair, made possible in cases of
natural or artificial genome redundancy.
PMID- 26442510
TI - The Origin of Mutants under Selection: Interactions of Mutation, Growth, and
Selection.
AB - The classical experiments of Luria and Delbruck showed convincingly that
mutations exist before selection and do not contribute to the creation of
mutations when selection is lethal. In contrast, when nonlethal selections are
used,measuring mutation rates and separating the effects of mutation and
selection are difficult and require methods to fully exclude growth after
selection has been applied. Although many claims of stress-induced mutagenesis
have been made, it is difficult to exclude the influence of growth under
nonlethal selection conditions in accounting for the observed increases in mutant
frequency. Instead, for many of the studied experimental systems the increase in
mutant frequency can be explainedbetter by the ability of selection to detect
small differences in growth rate caused by common small effect mutations. A
verycommon mutant class,found in response to many different types of selective
regimensin which increased gene dosage can resolve the problem, is gene
amplification. In the well-studiedlac system of Cairns and Foster, the apparent
increase in Lac+revertants can be explained by high-level amplification of the
lac operon and the increased probability for a reversion mutation to occur in any
one of the amplified copies. The associated increase in general mutation rate
observed in revertant cells in that system is an artifact caused by the
coincidental co-amplification of the nearby dinB gene (encoding the error-prone
DNA polymerase IV) on the particular plasmid used for these experiments. Apart
from the lac system, similar gene amplification processes have been described for
adaptation to toxic drugs, growth in host cells, and various nutrient
limitations.
PMID- 26442511
TI - Translation Initiation.
AB - Selection of correct start codons on messenger RNAs is a key step required for
faithful translation of the genetic message. Such a selection occurs in a complex
process, during which a translation-competent ribosome assembles, eventually
having in its P site a specialized methionyl-tRNAMet base-paired with the start
codon on the mRNA. This chapter summarizes recent advances describing at the
molecular level the successive steps involved in the process. Special emphasis is
put on the roles of the three initiation factors and of the initiator tRNA, which
are crucial for the efficiency and the specificity of the process. In particular,
structural analyses concerning complexes containing ribosomal subunits, as well
as detailed kinetic studies, have shed new light on the sequence of events
leading to faithful initiation of protein synthesis in Bacteria.
PMID- 26442508
TI - The DNA Exonucleases of Escherichia coli.
AB - DNA exonucleases, enzymes that hydrolyze phosphodiester bonds in DNA from a free
end, play important cellular roles in DNA repair, genetic recombination and
mutation avoidance in all organisms. This article reviews the structure,
biochemistry, and biological functions of the 17 exonucleases currently
identified in the bacterium Escherichia coli. These include the exonucleases
associated with DNA polymerases I (polA), II (polB), and III (dnaQ/mutD);
Exonucleases I (xonA/sbcB), III (xthA), IV, VII (xseAB), IX (xni/xgdG), and X
(exoX); the RecBCD, RecJ, and RecE exonucleases; SbcCD endo/exonucleases; the DNA
exonuclease activities of RNase T (rnt) and Endonuclease IV (nfo); and TatD.
These enzymes are diverse in terms of substrate specificity and biochemical
properties and have specialized biological roles. Most of these enzymes fall into
structural families with characteristic sequence motifs, and members of many of
these families can be found in all domains of life.
PMID- 26442509
TI - Assembly of Outer Membrane beta-Barrel Proteins: the Bam Complex.
AB - The major class of integral proteins found in the outer membrane (OM) of E. coli
and Salmonella adopt a beta-barrel conformation (OMPs). OMPs are synthesized in
the cytoplasm with a typical signal sequence at the amino terminus, which directs
them to the secretion machinery (SecYEG) located in the inner membrane for
translocation to the periplasm. Chaperones such as SurA, or DegP and Skp, escort
these proteins across the aqueous periplasm protecting them from aggregation. The
chaperones then deliver OMPs to a highly conserved outer membrane assembly site
termed the Bam complex. In E. coli, the Bam complex is composed of an essential
OMP, BamA, and four associated OM lipoproteins, BamBCDE, one of which, BamD, is
also essential. Here we provide an overview of what we know about the process of
OMP assembly and outline the various hypotheses that have been proposed to
explain how proteins might be integrated into the asymmetric OM lipid bilayer in
an environment that lacks obvious energy sources. In addition, we describe the
envelope stress responses that ensure the fidelity of OM biogenesis and how
factors, such as phage and certain toxins, have coopted this essential machine to
gain entry into the cell.
PMID- 26442512
TI - Primary stability of rotator cuff repair: can more suture materials yield more
strength?
AB - INTRODUCTION: It remains unclear if the increased biomechanical stability of the
double-row repair is solely a result of the technique itself or due to the
greater number of utilized materials. This study analyses the various rotator
cuff (RC) repair interfaces and the influence of doubling the number of suture
knots, stitch techniques and suture anchors on the primary stability of the RC
reconstruction. MATERIALS AND METHODS: Established cyclic testing protocols were
used to test the primary stability of the knot interface with a Duncan loop and
Roeder knot, the tendon-to-suture interface with a single-stitch and Mason-Allen
stitch and the anchor-to-bone interface with OPUS Magnum 2(r) and BioCorkscrew(r)
anchors. After doubling the materials, the interfaces were tested again and
compared to the yielded solitary values. The maximum failure loads (Fmax),
clinical failure (CF), system displacement (SD) and modes of failure were
recorded. RESULTS: Doubling the amount of knots, stitches and suture anchors
improved almost all interface parameters. For example, Fmax, CF and SD of the
Roeder knot could be significantly improved from 142.5 N to 256.7 N, from 82.5 N
to 155.0 N and from 0.45 mm to 0.20 mm, respectively. The Mason-Allen stitch's
Fmax improved from 196.4 N to 324.9 N, and CF from 94.25 N to 139.8 N, with
almost identical SD of 0.81 mm and 0.84 mm. Bio-Corkscrew(r) Fmax improved from
232.5 N to 317.5 N, CF from 182.5 N to 210 N, and SD from 0.85 mm to 0.64 mm.
CONCLUSION: Doubling the number of knots, stitches and suture anchors increases
the primary stability of the various RC repair interfaces and may result in RC
rerupture rate reduction. Furthermore, this study suggests that a suture anchor
loaded with two or three sutures may yield the same primary stability as two or
three suture anchors loaded with a single suture. This in vitro biomechanical
study focuses solely on the rotator cuff interfaces at time zero; the biological
healing process was therefore not analysed and requires further investigation.
CLINICAL RELEVANCE: Improved primary stability by increased number of suture
materials may reduce rate of RC rerupture.
PMID- 26442513
TI - Artocarpus altilis CG-901 alters critical nodes in the JH1-kinase domain of Janus
kinase 2 affecting upstream JAK/STAT3 signaling.
AB - As a key step in achieving low-cost, easily accessible anti-cancer therapy for
low- and middle-income countries, we recently established the scientific basis
for the folkloric use of Artocarpus altilis for the treatment of cancer by
investigating the geranyl dihydrochalcone (CG-901) content and its interference
with signal transducer and activator of transcription 3 (STAT3) phosphorylation
and blockage of further downstream signaling. In the current study, the CG-901
upstream target was queried by chemical fingerprinting similarity assessment,
semi-empirical (PM6ESCF) QMMM and molecular dynamics (MD) simulation. Moderate
(~0.4) to high (~0.7) Tanimoto scores were found when the CG-901 scaffold was
compared to ligands co-crystallized with Janus kinases (JAK) 1-3. High negative
energy values were obtained when the CG-901 was treated semi-empirically
(PM6ESCF) within the classical field of JAK (1-3). Multiple nanosecond MD
simulations showed that CG-901 did not cause any large structural perturbations
in the nucleotide-binding, activation and catalytic loops within the kinase (JH1)
domain of JAK (1-3); however, it reduced the energy required to attain
metastability along the path to energy minima conformation. In comparison to JAK1
and Apo-state JAK2, JAK2-bound CG-901 exhibited a highly re-organized key intra
domain protein network; indicating atomic level interference with inter-residue
communication. In conclusion, CG-901 isolated from A. altilis represents a broad
spectrum JAK inhibitor, which may underlie the mechanism of STAT3 phosphorylation
blockage. Graphical abstract Upper panel Janus kinase 2 upstream signaling
pathway. Lower panel Apo-JAK2 (left) and CG-901-bound JAK2 (right).
PMID- 26442514
TI - Effect of the association of 1-methyl-DL-tryptophan with paclitaxel on the
expression of indoleamine 2,3-dioxygenase in cultured cancer cells from patients
with breast cancer.
AB - Breast cancer is the most common type of cancer among women and the survival of
patients affected by it is increasing, mainly due to several new approaches in
early diagnosis and more effective treatments. The enzyme indoleamine 2,3
dioxygenase (IDO) is expressed in many cells, including tumor cells. IDO acts by
inhibiting the proliferation of T lymphocytes, thus compromising their cytotoxic
activity. 1-Methyl-DL-tryptophan (1MT) is a competitive inhibitor of IDO, which
blocks its immunosuppressive effect. Paclitaxel is an antineoplastic drug largely
used in breast cancer therapy. Thus, this study aimed to determine the in vitro
effect of the association of 1MT and paclitaxel chemotherapy, as an approach to
reduce tumor growth. It is believed that this would allow the restoration of T
lymphocyte proliferation capability and its cytotoxic response. The supplemented
cultures showed that the most significant differences in the expression of IDO
were observed in the group treated with paclitaxel associated with 1-MT
continuous supplementation, reducing enzyme expression from 12.06 to 3.56 %. This
association was more effective in reducing IDO expression and could collaborate
in developing a new therapeutic strategy for breast cancer treatment.
PMID- 26442516
TI - Nocardioides glacieisoli sp. nov., isolated from a glacier.
AB - A Gram-stain-positive, rod-shaped, non-spore-forming bacterium (strain HLT3-15T)
was isolated from the ice tongue surface of the Hailuogou glacier in Szechwan
Province, PR China. Phylogenetic analysis, based on 16S rRNA gene sequences,
revealed that strain HLT3-15T belonged to the genus Nocardioides. The highest
levels of sequence similarities were found with Nocardioides hwasunensis CGMCC
4.6881T and Nocardioides ganghwensis CGMCC 4.6875T (98.5 % and 98.3 %,
respectively). However, DNA-DNA relatedness demonstrated that strain HLT3-15T was
distinct from its closest phylogenetic neighbours. The major cellular fatty acids
of strain HLT3-15T were C17 : 1omega8c and iso-C16 : 0. Strain HLT3-15T contained
ll-2,6-diaminopimelic acid as the diamino acid in the cell-wall peptidoglycan and
MK-8(H4) as the predominant menaquinone. On the basis of a polyphasic approach, a
novel species, Nocardioides glacieisoli sp. nov., is proposed with HLT3-15T ( =
CGMCC 1.11097T = NBRC 109781T) as the type strain.
PMID- 26442517
TI - Biosimilar versions of anti-TNF drugs could save NHS money, drug company claims.
PMID- 26442515
TI - Clinicopathologic characteristics of anterior prostate cancer (APC), including
correlation with previous biopsy pathology.
AB - Anterior-predominant prostate cancer (APC) is an incompletely understood entity
which can be difficult to sample via transrectal biopsy. Seemingly favorable
biopsy results may belie the potential aggressiveness of these tumors. Here, we
attempt to characterize APC by retrospectively examining the clinicopathologic
features of APC at radical prostatectomy and comparing our findings with prior
biopsy information. We found that 17.4 % of patients in our study had APC. APC
demonstrated a significantly lower (P value < 0.05) Gleason score (GS) and
pathologic stage than non-APC tumors, including the absence of seminal vesicle
invasion by APC. A subset (5.6 %) of APC consisted of high-grade tumors (GS >=
8), and these tumors were more often detected on transperineal saturation biopsy
than non-transperineal saturation (i.e., transrectal ultrasound guided) biopsy
strategies. Four patients (7 %) without transperineal saturation biopsy exhibited
a significantly worse GS at RP than biopsy, compared to five patients (36 %) with
transperineal saturation biopsy. Our findings corroborate the difficulty in
detecting APC and suggest that APC is not a uniform disease with a wholly
indolent phenotype. Dedicated long-term outcome data are needed in these
patients. Additionally, alternative pathologic staging parameters may be
necessary.
PMID- 26442518
TI - Time to invest in developing community mental health services.
AB - OBJECTIVES: To report on the evaluation of publicly funded community mental
health services in two New South Wales health districts. METHODS: Qualitative and
quantitative data from 28 publicly funded adult community mental health teams in
two NSW health districts were gathered using structured interviews, benchmarking
surveys, focus groups and online questionnaires. RESULTS: The community mental
health services studied lacked a coherent strategic and recovery oriented
framework or model of care for service delivery. There was evidence of poor role
definition at the team level, resulting in duplication and inefficiency. There
were inadequate staffing levels for stated objectives, a lack of training and
continuing education in evidence based intervention, poor consumer and family
participation in service design, and no development and monitoring of meaningful
outcome measures. CONCLUSIONS: This review and benchmarking study highlights the
need for mental health policy implementation to be further supported with:
development of a service delivery framework outlining essential components of a
specialist community mental health system; operational guidance to enable
effective team specialisation in accordance with research; investment in
practitioner training to support the development of evidence based practice; and
processes to ensure effective consumer and carer participation in developing
recovery oriented services.
PMID- 26442519
TI - Transcranial direct current stimulation in the male mouse to promote recovery
after stroke.
AB - Transcranial direct current stimulation (tDCS) constitutes a promising approach
for promoting recovery of function after stroke, although the underlying
neurobiological mechanisms are unclear. To conduct translational research in
animal models, stimulation parameters should not lead to neuronal lesions.
Liebetanz et al. recommend charge densities for cathodal stimulation in rats, but
parameters for mice are not established. We established tDCS in the wild-type
mouse, enabling studies with genetically-engineered mice (GEM). tDCS equipment
was adapted to fit the mouse skull. Using different polarities and charge
densities, tDCS was safe to apply in the mouse where the charge density was below
198 kC/m(2) for single or repeated stimulations. These findings are crucial for
future investigations of the neurobiological mechanisms underlying tDCS using
GEM.
PMID- 26442521
TI - Body Mass Index, Outcomes, and Mortality Following Cardiac Surgery in Ontario,
Canada.
PMID- 26442520
TI - Neoplastic cauda equina syndrome: a neuroimaging-based review.
AB - Cauda equina syndrome refers to dysfunction of the cauda equina, the collection
of ventral and dorsal lumbar, sacral and coccygeal nerve roots that surround the
filum terminale. This most commonly occurs as a result of compression by a
herniated lumbosacral disc. However, the syndrome may also complicate metastatic
cancer or a primary neoplasm within or infiltrating the spinal canal. An accurate
and timely diagnosis is critical to avoid irreversible loss of neurological
function. The clinician and radiologist must therefore be aware of the many
possible causes to guide timely management. Here we review the diverse neoplastic
causes affecting the cauda equina nerve roots from a neuroimaging-based
perspective. We divide them by location into intramedullary neoplasms at the
conus (such as astrocytoma), intradural-extramedullary neoplasms (such as
schwannoma and leptomeningeal metastases) and extradural neoplasms (such as
spinal metastases from systemic neoplasms). We also discuss the clinical features
associated with cauda equina tumours, with special focus on cauda equina
syndrome.
PMID- 26442522
TI - Pursuing a Desired Future: Continuity and Change in a Long-Term-Care Community.
AB - New ways of planning, assessing, and measuring cultural change are needed in long
term care. Much effort is focused on person-centered care; less attention is paid
to achieving localized change. Long-term-care communities need innovative
approaches for identifying local cultural features to preserve and others to
reconfigure. This case study involves applied anthropologists working with four
stakeholder groups-residents, staff, family members, and volunteers-to document
views of their "culture story" and conceptualize a cultural ideal for their
community. Based on strengths and weaknesses from their culture story, specific
recommendations were made to maintain their strong relationship focus, expand
community outreach, and improve staff relations. Incorporating "insider" views of
the past, present, and imagined future and building on current "best practices"
of the culture-change movement are two distinctive but complementary approaches
for motivating and managing cultural change.
PMID- 26442523
TI - Integrated Pharmacokinetic/Pharmacodynamic Analysis for Determining the Minimal
Anticipated Biological Effect Level of a Novel Anti-CD28 Receptor Antagonist BMS
931699.
AB - BMS-931699 (lulizumab pegol), a domain antibody (dAb) conjugated with 40-kDa
branched polyethylene glycol, is a human anti-CD28 receptor antagonist under
development for the treatment of inflammatory and autoimmune diseases. In the
present work, the minimal anticipated biologic effect level (MABEL) was
determined for BMS-931699 by integrating all the available preclinical data. The
relevance of the in vitro mixed lymphocyte reaction (MLR) assay to a whole blood
CD28 receptor occupancy (RO) assessment, as well as the relationship between the
CD28 RO and the inhibition of T-cell-dependent antibody response to keyhole
limpet hemocyanin in vivo, was demonstrated through an integrated
pharmacokinetic/pharmacodynamic analysis using anti-hCD28 dAb-001 (differing from
BMS-931699 by two additional amino acids at the N-terminus) and a mouse
surrogate. Based on this analysis, the EC10 value (0.32 nM) from the human MLR
assay and the human plasma volume (0.04 l/kg) were employed to calculate the
MABEL (0.01 mg) of BMS-931699 in humans, with a CD28 RO predicted to be <=10%.
The estimated MABEL dose was threefold higher than the value derived from the
binding constant and twofold less than the MABEL converted from animal efficacy
studies based on the body surface area. Furthermore, it was 2900-fold lower than
the human equivalent dose derived from the no observed adverse effect level in
monkeys (15 mg/kg/week for 5 doses, intravenous dosing) with a 10-fold safety
factor applied. Therefore, the MABEL dose represented a sound approach to
mitigate any potential risk in targeting CD28 and was successfully used as the
first-in-human starting dose for BMS-931699.
PMID- 26442524
TI - MicroRNA-218 is a prognostic indicator in colorectal cancer and enhances 5
fluorouracil-induced apoptosis by targeting BIRC5.
AB - One major reason for the failure of advanced colorectal cancer (CRC) treatment is
the occurrence of chemoresistance to fluoropyrimidine (FU)-based chemotherapy.
Various reports showed that ectopic expression and function of microRNAs (miRNAs)
played key roles to mediate apoptosis at the post-transcriptional level. To
further explore the possible mechanisms, we evaluated the prognostic effect of
miR-218 in patients with CRC receiving 5-FU-based treatment and investigated the
proapoptotic role of miR-218 in vitro. Primary tumour specimens and adjacent non
tumour sites were used to determine miR-218 expression distribution and explore
its potential prognostic value in response to 5-FU-based treatment in patients
with CRC. HCT116 and HT29 cells were transfected with precursor miR-218 or
negative control, followed by assays to investigate its influence on apoptosis,
cell proliferation and pathways involved in molecular mechanisms of
chemoresistance to 5-FU. Results showed that high miR-218 expression was
associated with positive response to firstline 5-FU treatment in CRC patients.
MiR-218 promoted apoptosis, inhibited cell proliferation and caused cell cycle
arrest in CRC cells by suppressing BIRC5 expression. Furthermore, miR-218
enhanced 5-FU cytotoxicity in CRC cells by suppressing the 5-FU targeted enzyme,
thymidylate synthase (TS). In conclusion, we demonstrated that high miR-218
expression had a positive prognostic value in 5-FU-based treatments for CRC
patients and discovered a novel mechanism mediated by miR-218 to promote
apoptosis and to function synergistically with 5-FU to promote chemosensitivity
by suppressing BIRC5 and TS in CRC. These suggest the unique potential of miR-218
as a novel candidate for developing miR-218-based therapeutic strategies in CRC.
PMID- 26442525
TI - Restoration of paclitaxel resistance by CDK1 intervention in drug-resistant
ovarian cancer.
AB - Epithelial ovarian cancer (EOC) commonly acquires resistance to chemotherapy, and
this is the major obstacle to the better prognosis. Elucidating the molecular
targets altered by chemotherapy is critically required to understand and overcome
drug resistance. As a drug combination including paclitaxel is a prevalent
prescription for treatment of EOC, to uncover gene expression altered in
paclitaxel-resistant EOC, we analyzed multidirectional microarray profiles in
both EOC cell lines and patients with paclitaxel resistance. Cyclin-dependent
kinase 1 (CDK1) was found to be a potential target of transcription factors to
regulate paclitaxel resistance. As a result of the subsequent pharmacogenomics
analysis, CDK1 inhibitor alsterpaullone was also indicated as a promising
chemical that may be used in combinatorial therapies to reverse paclitaxel
induced chemoresistance. Although a CDK1 inhibitor has the potential to kill
cancer cells, short-term treatment over 2 weeks at sublethal doses effectively
induced cell death only upon additional treatment with paclitaxel. A prominent
reduction in the tumor growth rate was observed upon paclitaxel subsequent to
alsterpaullone treatment in EOC xenograft model. Thus, we suggest that inhibition
of CDK1 with alsterpaullone may be a novel therapeutic method to reverse
paclitaxel-induced resistance in ovarian cancer cells.
PMID- 26442526
TI - Assessment of transthoracic ultrasound diagnosis of ovine pulmonary
adenocarcinoma in adult sheep.
AB - Ovine pulmonary adenocarcinoma (OPA), caused by Jaagsiekte sheep retrovirus
(JSRV), is a disease of increasing concern in the sheep industry. There is no
commercial antemortem test for OPA; therefore, an early evaluation phase study
was undertaken to examine the accuracy of transthoracic ultrasound examination
using a 5-6.5 MHz sector ultrasound machine widely available in veterinary
practice in the UK to diagnose OPA. Restraint, preparation and examination time
was restricted to five minutes per sheep to represent the cost limitations of
commercial sheep farming. One hundred sheep were examined. All 41 cases
identified with suspect OPA lesions during transthoracic ultrasound examination
had the diagnosis confirmed at postmortem examination, while sheep without
ultrasonographic changes characteristic of OPA had no gross lesions of OPA at
postmortem examination. This demonstrates the specificity of transthoracic
ultrasound for diagnosis of OPA. The authors propose that, in the absence of any
other reliable preclinical diagnostic test, the use of transthoracic ultrasound
examination should be considered for a second opinion on an initial diagnosis of
OPA, for screening purchased adult flock replacements for OPA, or for screening
sheep in a known OPA-affected flock. However, the authors emphasise that a
negative scan cannot provide a guarantee that the animal is free of JSRV
infection nor early OPA.
PMID- 26442527
TI - Enucleation in equids with and without the use of an orbital suture meshwork
implant: a retrospective study of 37 cases.
AB - This retrospective study on 37 horses was conducted to assess long-term
complications, scarring, cosmetic appearance and owner satisfaction of horses
that underwent transpalpebral enucleation with (n=26) or without (n=11) non
absorbable sutured meshwork prosthesis between 2006 and 2013. Postoperative
complications related to the surgery were wound infection, discharge and
dehiscence, and no significant difference between groups was found. In one horse,
the meshwork had to be removed in order to treat a chronic fistula. Horses with
infection or inflammation before surgery were more likely to encounter
postoperative complications, whether or not a meshwork was used. Most owners were
satisfied by the surgical technique for scarring, but contrary to the present
hypothesis, most horses with a meshwork implant had a poor sunken-in appearance,
and 26 per cent of owners would like to attempt other techniques to improve the
cosmetic result. Also, a further 44 per cent of owners would prefer a better
cosmetic result if the technique does not increase complication risk or cost.
Meshwork implant prosthesis after transpalpebral enucleation was safe. However,
in order to achieve a better cosmetic result, further improvements of the
technique will be required.
PMID- 26442530
TI - The Effect of Levetiracetam on Closure of the Midline in Early Chicken Embryos.
AB - AIM: Genetic predisposition and some environmental factors play an important role
in the development of neural tube defects. Levetiracetam is a new drug that has
been approved in the treatment of partial seizures. We aimed in this study to
determine the effect of levetiracetam on chick embryos. MATERIAL AND METHODS: One
hundred and sixty fertile non-pathogenic Super Nick eggs were incubated for 24
hours and were divided into four groups of 40 eggs each. Levetiracetam was
administered via the sub-blastodermic route. The eggs were incubated for another
24 hours. All eggs were opened at the 48th hour, and the embryos were evaluated
morphologically and histopathologically. RESULTS: The effects of levetiracetam on
the embryo were correlated with the dose of levetiracetam. In the light of the
results, it was determined that the use of increasing doses of levetiracetam led
to defects of midline closure in early chicken embryos. CONCLUSION:
Levetiracetam, a new antiepileptic drug that is effective especially on calcium
ion concentration, leads to defects in midline closure in embryos in a dose
dependent manner. Further studies are needed to show the mechanism of embryonic
damage and the mechanisms of its teratogenous effects associated with genetic and
environmental factors.
PMID- 26442531
TI - Lumbar Microdiscectomy Under Spinal and General Anesthesia: A Comparative Study.
AB - AIM: To compare the safety and efficacy of spinal anesthesia (SA) in patients
undergoing lumbar microdiscectomy (LM). MATERIAL AND METHODS: We evaluated 180
patients who underwent LM between 1 January 2012 and 5 July 2013. Demographic,
clinical, laboratory, and pre-, intra-, and postoperative information was
determined from the patients' medical records. RESULTS: Total anesthetic times
were longer in the general anesthesia (GA) group. There was less bleeding at the
surgical site in the SA group. Intraoperative blood pressure was significantly
also lower in the SA group. Meanwhile, tachycardia was significantly higher in
the GA group. The analgesic requirement in post-anesthesia care unit (PACU) was
higher in the general anesthesia group. At PACU admission, analgesic requirement,
heart rate, and the mean arterial pressure were higher in the GA group.
Postoperative nausea and vomiting was more frequent among patients recovering in
general anesthesia group. SA patients had an increased incidence of urinary
retention compared with GA patients. Pulmonary complications requiring specific
treatment were insignificantly higher among GA patients. CONCLUSION: In patients
who undergo lumbar disc surgery, SA is a good alternative for experienced
surgeons because of a more comfortable healing process.
PMID- 26442532
TI - Clinical Features and Surgical Treatment of Aggressive Meningiomas.
AB - AIM: To explore the clinical features and surgical treatment of aggressive
meningiomas (AMs). MATERIAL AND METHODS: Samples from 55 patients with AMs were
analyzed, and their clinical characteristics, molecular biological mechanism, and
surgical treatment were studied in combination with the literature. RESULTS: The
main clinical and imaging features of AMs included manifestations of local
structures invaded by tumors, frequently irregular or flat tumors in shape, more
obvious cerebral edema surrounding the tumors, seldom calcification of tumor,
more frequent and typical dural tail sign, often absent white or black ring sign,
partial or complete occlusion of venous sinus and hyperplasia and destruction of
local skull. Simpson I resection was achieved in 31 cases, II in 13, III-IV in
11. No severe complications and death occurred after operation. CONCLUSION: AMs
have prominent clinical features. Appropriate surgery can provide a good
therapeutic effect.
PMID- 26442528
TI - Genomes to natural products PRediction Informatics for Secondary Metabolomes
(PRISM).
AB - Microbial natural products are an invaluable source of evolved bioactive small
molecules and pharmaceutical agents. Next-generation and metagenomic sequencing
indicates untapped genomic potential, yet high rediscovery rates of known
metabolites increasingly frustrate conventional natural product screening
programs. New methods to connect biosynthetic gene clusters to novel chemical
scaffolds are therefore critical to enable the targeted discovery of genetically
encoded natural products. Here, we present PRISM, a computational resource for
the identification of biosynthetic gene clusters, prediction of genetically
encoded nonribosomal peptides and type I and II polyketides, and bio- and
cheminformatic dereplication of known natural products. PRISM implements novel
algorithms which render it uniquely capable of predicting type II polyketides,
deoxygenated sugars, and starter units, making it a comprehensive genome-guided
chemical structure prediction engine. A library of 57 tailoring reactions is
leveraged for combinatorial scaffold library generation when multiple potential
substrates are consistent with biosynthetic logic. We compare the accuracy of
PRISM to existing genomic analysis platforms. PRISM is an open-source, user
friendly web application available at http://magarveylab.ca/prism/.
PMID- 26442529
TI - NCLscan: accurate identification of non-co-linear transcripts (fusion, trans
splicing and circular RNA) with a good balance between sensitivity and precision.
AB - Analysis of RNA-seq data often detects numerous 'non-co-linear' (NCL)
transcripts, which comprised sequence segments that are topologically
inconsistent with their corresponding DNA sequences in the reference genome.
However, detection of NCL transcripts involves two major challenges: removal of
false positives arising from alignment artifacts and discrimination between
different types of NCL transcripts (trans-spliced, circular or fusion
transcripts). Here, we developed a new NCL-transcript-detecting method
('NCLscan'), which utilized a stepwise alignment strategy to almost completely
eliminate false calls (>98% precision) without sacrificing true positives,
enabling NCLscan outperform 18 other publicly-available tools (including fusion-
and circular-RNA-detecting tools) in terms of sensitivity and precision,
regardless of the generation strategy of simulated dataset, type of intragenic or
intergenic NCL event, read depth of coverage, read length or expression level of
NCL transcript. With the high accuracy, NCLscan was applied to distinguishing
between trans-spliced, circular and fusion transcripts on the basis of poly(A)-
and nonpoly(A)-selected RNA-seq data. We showed that circular RNAs were expressed
more ubiquitously, more abundantly and less cell type-specifically than trans
spliced and fusion transcripts. Our study thus describes a robust pipeline for
the discovery of NCL transcripts, and sheds light on the fundamental biology of
these non-canonical RNA events in human transcriptome.
PMID- 26442533
TI - Vena Cava Filters are not Superior to Low Molecular Weight Heparin in Venous
Thromboembolism Prophylaxis: A Study on Long-Term Immobilized Neurosurgical
Patients.
AB - AIM: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are the most
frequent surgical problems and associated with high morbidity and mortality.
Neurosurgical patients constitute a unique group where prophylaxis with
anticoagulant and antiaggregant agents are relatively contraindicated due to the
natural course of vascular problems such as aneurysms, hemorrhagic tumors or
hematomas or increased vulnerability to complex spinal surgeries and trauma.
MATERIAL AND METHODS: We included 67 patients predicted to be immobilized for 2
or more months in this retrospective analysis. A vena cava filter was inserted
between the first and seventh postoperative day in 40 patients in a prophylactic
manner whereas 27 patients received low dose heparin for the same purpose. The
patients were evaluated for symptomatic DVT or PE. RESULTS: Percutaneous
insertion was performed for all filters without any complication. DVT occurred in
two patients of the filter group and 1 patient of the heparin group. There was no
PE recorded in any patient of either group. Patients were followed up for 22
months in the filter and 16 months in the heparin group. CONCLUSION: We conclude
that prophylactic filter use in high risk neurosurgical patients is not
beneficial and not superior to low-molecular-weight heparin use. Nevertheless, it
is reasonable to prevent PE in patients with proven DVT who have no
contraindication for anticoagulant drugs.
PMID- 26442534
TI - The Role of Wrist Magnetic Resonance Imaging in the Differential Diagnosis of the
Carpal Tunnel Syndrome.
AB - AIM: The carpal tunnel syndrome (CTS) is the commonest compressive neuropathy.
Electromyography (EMG) is accepted as gold standard in diagnosis of CTS. However,
pathologies and variations that are associated with a various findings may lead
to failure. MATERIAL AND METHODS: Magnetic resonance Imaging (MRI) was applied to
69 wrists of 55 patients, who received a diagnosis of CTS by means of clinical
and electrodiagnostic testing (EDT) during the years 2011 and 2013. RESULTS: We
detected a total of 71 additional pathologies in MRI analyses: 29 degenerative
bone cysts, 28 ganglion cysts, 8 tenosynovitis, and 6 avascular necroses. While
the MRI detected 44 (59.5%) additional radiological pathologies in 39 wrists
diagnosed with mid-level CTS by means of EMG, the number of detected additional
pathologies was 27 (36.5%) in 30 wrists diagnosed with advanced-level CTS.
CONCLUSION: Wrist MRI is an effective means to reveal associated pathologies in
patients diagnosed with CTS by means of clinical testing and EDT. Additional
pathologies may not only change the applicable type of surgery, but also decrease
the number of postoperative failures. Wrist MRI is recommended, especially for
young cases with unilateral CTS history accompanied by dubious clinical symptoms
and lacking any pronounced predisposing factors.
PMID- 26442535
TI - Use of SpongostanTM for Prevention of Cranial Subdural Adhesions Following
Craniotomy in an Experimental Rabbit Model.
AB - AIM: SpongostanTM is a sterile, water-insoluble, porcine gelatin absorbable
sponge, which is widely used as a hemostatic material. The aim of this study is
to test the anti-fibrotic capacity of SpongostanTM, using a craniotomy model in
an experimental rabbit model. MATERIAL AND METHODS: Eighteen rabbits were divided
into two groups: Each group consisted of 9 rabbits, duratomy plus SpongostanTM
(group 1), and duratomy without SpongostanTM (group 2). Right parietal bone was
removed via trephine and low speed drill and dura was opened. On the group 1
rabbits, an appropriate piece of SpongostanTM was meticulously placed under dural
layer. On group 2 rabbits, same procedures were repeated without SpongostanTM.
Histological sections were taken from each group and evaluated for degree of
fibrosis and collagen fibers. RESULTS: There was marked increase in number of
fibroblasts and collagen fibers in group 2 rabbits, however most of the rabbits
in SpongostanTM group demonstrate scarce histopathological findings for fibrosis.
CONCLUSION: We conclude that an appropriately placed subdural SpongostanTM over
cerebral tissue may prevent postoperative surgical adhesions after neurosurgical
operations.
PMID- 26442536
TI - Surgical Management of Moderate Sized Spontaneous Cerebellar Hematomas: Role of
Intracranial Pressure Monitoring.
AB - AIM: Acute onset spontaneous cerebellar hematoma (SCH) is a neurosurgical
emergency with unpredictable natural history and outcome. Specific guidelines are
available for management of small ( < 2.5 cm) and large sized (4.0 cm < ) SCH.
But, literature is sparse for treatment of moderate sized SCH (2.5-4.0 cm).
MATERIAL AND METHODS: In a retrospective analysis of 32 patients, with moderate
sized acute SCH, external ventricular drainage (EVD) tube was inserted for
evaluation of ICP and evacuation of cerebrospinal fluid. All patients with ICP >
25 mmHg underwent emergency SCH evacuation. Postoperatively, EVD was continued
for 48-72 hours for ICP monitoring. Patients showing no improvement or persistent
ventriculomegaly underwent ventriculoperitoneal shunt (VPS) insertion for the
management of hydrocephalus. RESULTS: 29/32 patients needed operative
intervention either in the form of hematoma evacuation or shunt placement. 10
patients improved to GOS 5 and 7 to GOS 4. Overall mortality was 25% (n=8).
Despite SCH evacuation, none of the patients with ICP > 40 mmHg experienced good
outcome (p < 0.0001). CONCLUSION: 47% of patients with moderate sized SCH need
surgical evacuation. EVD insertion not only helps in ICP management but also
includes the ability to gradually decompress ventricular system by varying the
outflow pressure. Apart from radiologic findings, ICP measurement should be a
guideline in management decisions.
PMID- 26442537
TI - Deep Brain Stimulation of the Rat Subthalamic Nucleus Induced Inhibition of
Median Raphe Serotonergic and Dopaminergic Neurotransmission.
AB - AIM: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) relieves motor
dysfunction in advanced Parkinson's disease (PD). However, STN DBS treated
patients can experience unpleasant and debilitating psychiatric side effects such
as depression and impulsivity. The neural basis of these psychiatric effects has
been linked to a dysfunction of 5-hydroxytryptamine (5-HT, serotonin)
neurotransmission. STN DBS inhibited activity of 5-HT cell bodies in the dorsal
raphe nucleus (DRN). Another important 5-HT source is located in the median raphe
nucleus (MRN), which also contains a population of dopamine neurons. The effects
of STN DBS on the MRN are unknown. Here, we test the hypothesis that STN DBS
reduces 5-HT and dopaminergic function in the MRN, which may contribute to the
psychiatric side effects of STN stimulation. MATERIAL AND METHODS: Bilateral STN
DBS was applied in a freely moving rat model. Following STN DBS, rats were
sacrificed and the brains were processed for c-Fos, 5-HT and tyrosine hydroxylase
(TH) immunohistochemistry. RESULTS: We found that STN DBS significantly lowered c
Fos expression compared to non-stimulated controls indicating reduced neuronal
activity. Moreover, the mean optical density values of 5-HT and TH cells in the
MRN was significantly lower compared to controls. CONCLUSION: These results show
that STN DBS inhibits 5-HT and dopamine neurotransmission in the MRN.
PMID- 26442538
TI - Surgical Exposure Gained in an Extended Retrosigmoid Approach to the
Cerebellopontine Angle Compared to the Traditional Retrosigmoid Approach.
AB - AIM: Retrosigmoid approach to the posterior fossa has been a popular and
dependable approach for accessing the cerebellopontine angle (CPA) and
petroclival region. Although this approach is commonly used, it requires
cerebellar retraction and has limitations when the lesion is located ventral to
the brainstem. The aim was to quantify the angle of view provided by extended
retrosigmoid approach in comparison to the traditional approach. A secondary
objective was to identify a strategic initial burr hole site for craniotomy.
MATERIAL AND METHODS: Ten adult human cadaver heads (20 sides) were used. First,
traditional retrosigmoid approach was performed and the angle of exposure was
measured on cranial computerized tomography (CT). Following, extended
retrosigmoid approach was performed with mastoid bone drilling and reflection of
venous sinuses. Angle of exposure was measured on CT. Two measurements of both
approaches were compared. RESULTS: Mean angle of view for the traditional
retrosigmoid approach (31.4 degrees +/- 4.1 degrees ) was significantly smaller
than that of the extended approach (46.0 degrees +/- 4.7 degrees ) (p < 0.001).
Site of strategic burr hole was 5 mm below and 15 mm lateral to the asterion was
defined. CONCLUSION: Extended retrosigmoid approach offers neurosurgeons
approximately 50% larger angle of view and shorter working distance than the
traditional approach provides. This modification permits better access to the CPA
and ventral brain stem without cerebellar retraction.
PMID- 26442539
TI - Fusiform Enlargement of the Superficial Temporal Artery in the Cases with
Intracranial Aneurysm.
AB - AIM: The superficial temporal artery is one of the main terminal branches of the
external carotid artery. This artery ascends through the lateralposterior margin
of the zygomatic arch to reach the temporal region of the scalp. The superficial
temporal artery divides its frontal and parietal branches around the zygomatic
arch. MATERIAL AND METHODS: The raw data of the Three-dimensional Computerized
Tomography Angiography (3D-CTA) were transferred to computer and recorded in a
software program. This software program created the three-dimensional images of
the superficial temporal artery using these transferred raw data with volume
rendering technique. RESULTS: Fifteen cases (5 female and 10 male, mean age 54.26
+/- 12.35 years) with intracranial aneurysm were evaluated in terms of the type,
location and dimensions of the fusiform enlargements. Fusiform enlargement was
bilateral in eleven of the cases. Remaining four cases have unilateral fusiform
enlargement of the superficial temporal artery. CONCLUSION: Fusiform enlargement
of the superficial temporal artery may be seen in the cases with intracranial
aneurysms. 3D-CTA should be carefully evaluated in the demonstration of
extracranial-intracranial vascular pathologies.
PMID- 26442540
TI - Role of Post-Decompressive Hydrocephalus in Patients with Malignant Cerebral
Infarction.
AB - AIM: The association between post-decompressive hydrocephalus and clinical
neurological expression is still unclear. In order to investigate this
relationship, the authors analyze series of ventricular morphology and level of
consciousness at different clinical stages for patients accepting decompressive
craniectomy (DC). MATERIAL AND METHODS: From 2005 to 2011, 13 patients accepting
DC under the diagnosis of malignant cerebral infarction were retrospectively
evaluated in terms of ventricular frontal horn dilatation and level of
consciousness, Glasgow Coma Scale score, at four different clinical stages: 1):
pre-DC stage; 2): post-DC stage while stabilization; 3): post-cranioplasty stage;
4): post-shunt stage [for those with permanent cerebrospinal fluid (CSF)
diversion]. RESULTS: All 13 patients had ventricular dilatation and two of them
had extra-axial CSF collection. Restoration of ventricular dilatation was not
observed in all patients after bone flap placement, but extra-axial CSF
collection resorbed spontaneously. Four patients accepting permanent CSF
diversion had no improvement over neurological expression. Otherwise, two of them
complicated with subdural effusion after shunt placement. CONCLUSION:
Decompressive craniectomy itself would lead to ventricular dilatation
universally. There is no direct association between degree of ventriculomegaly
and neurological expression. Permanent CSF diversion surgery as treatment for
ventriculomegaly makes no clinical improvement with possible complications of
overshunting.
PMID- 26442541
TI - Increased Expression of Matrix Metalloproteinase-9 in Patients with Temporal Lobe
Epilepsy.
AB - AIM: The molecular mechanism of epileptogenesis in temporal lobe epilepsy is
still unclear. Experimental studies have suggested that matrix metalloproteinases
have important roles in this process, but human studies are limited. The aim of
this study was to assess the expression of MMP-9, MMP-2 and their tissue
inhibitors (TIMP-1 and TIMP-2) in patients with temporal lobe epilepsy with
hippocampal sclerosis (TLE-HS). MATERIAL AND METHODS: The tissue samples from
temporal neocortex and hippocampus were obtained from patients with temporal lobe
epilepsy with hippocampal sclerosis who had undergone anterior temporal lobectomy
for recurrent medically resistant seizures. Immunohistochemical methods were used
to determine the expression of MMP-9, MMP-2 and their tissue inhibitors. Tissue
samples were also analyzed with transmission electron microscopy. RESULTS: The
immunoreactivity for MMP-9 both in hippocampal and temporal neocortical neurons
was stronger than that of MMP-2. Additionally, there was a mild reaction for its
tissue inhibitor TIMP-1 as with TIMP-2. The TEM analysis of the hippocampus
revealed that there was apparent ultra-structural damage on the pericarya and
neuropil of some neurons. There was obvious damage in the mitochondria and the
nuclear membrane. CONCLUSION: The preliminary results of this study revealed that
MMP-9 may have a role in patients with drug resistant TLE-HS.
PMID- 26442542
TI - Effect of Montelukast on Spinal Cord Ischemia- Reperfusion Injury.
AB - AIM: Paraplegia due to ischemia-reperfusion (I/R) injury of the spinal cord is a
devastating complication of thoracoabdominal aortic surgery. Cysteinyl
leukotrienes are potent mediators of inflammation that are associated with I/R
injury. The present study was designed to investigate the role of montelukast, a
selective reversible CysLT1 receptor antagonist, on spinal cord I/R injury in an
experimental model. MATERIAL AND METHODS: Twenty-one male Sprague-Dawley rats
were randomly assigned to three groups (n=7 per group) as G1 (no aortic occlusion
and montelukast administration), G2 (45 min. aortic occlusion; no montelukast
administration) and G3 (45 min. aortic occlusion, 10 mg/kg montelukast
administration). After neurologic evaluation using the Motor Deficit Index (MDI)
score at the 48th hour of reperfusion, lumbar spinal cords were removed for
histopathological evaluation and immunohistochemical staining for HSP70,
interleukin-6 and myeloperoxidase (MPO). RESULTS: All rats in the G1 group had a
normal neurological status and their MDI score was 0 (p < 0.05). The MDI score of
G3 was significantly lower than G2 group (2.8 vs. 5.5; p < 0.05). Vacuolar
congestion was found to be significantly lower in G1 than the other groups
(p=0.0001). The interleukin-6 receptor level was found to be significantly lower
in G3 group than the control group (p=0.013). There was no statistically
significant difference found among the groups in terms of the degree of HSP70 and
MPO staining. CONCLUSION: Increased generation of leukotrienes in postischemic
organs play an important role in I/R injury. The findings of the current study
demonstrated that montelukast improved motor recovery and decreased IL-6 levels
in spinal cord I/R injury.
PMID- 26442543
TI - Percutaneous Laser Disc Decompression: Retrospective Analysis of 197 Cases and
Review of The Literature.
AB - AIM: Percutaneous laser disc decompression (PLDD) is a one of the well-known
minimal invasive treatment methods of disc herniations. The aim of this study is
to present our clinical experience and to show the benefits of this technique.
MATERIAL AND METHODS: A total of 197 patients, who met the criteria of PLDD,
underwent treatment between 2007 and 2009. The data of the patients was reviewed
retrospectively. Among them, 107 (54.3 %) patients were male and 90 were female
with a mean age of 46.34 years (ranged between 23 and 86 years). Seventy-two
patients underwent one level PLDD, 112 (56.8 %) patients two levels PLDD and 13
patients three levels PLDD procedures. The mean follow-up time was 42 months.
RESULTS: Among the 72 patients, the level of PLDD was L3-L4 in 4 patients, L4-L5
in 39 patients and L5-S1 in 29 patients. L4-L5 and L5-S1 levels were the most
common 2-level PLDD locations in 71 patients. Twenty-five (12.7 %) patients
underwent microsurgical discectomy after PLDD. The procedure was repeated in 3
patients. Discitis secondary to possible thermal injury occurred in 2 (0.1%)
patients and this complication was improved with conservative treatment.
CONCLUSION: PLDD is a safe and effective procedure in the treatment of discogenic
pain if the patient met the selection criteria. However, this technique is not an
alternative to open surgery.
PMID- 26442544
TI - Posterior Lumbar Stabilization Surgery under Spinal Anesthesia for High-Risk
Patients with Degenerative Spondylolisthesis, Spinal Stenosis and Lumbar
Compression Fracture.
AB - AIM: Spinal anesthesia is an appropriate technique for lumbar spine surgeries of
two to three hours duration. The aim of this study is to document our experience
on spinal anesthesia administered to the patients with degenerative lumbar spine.
MATERIAL AND METHODS: A total of 497 patients underwent spinal stabilization
surgery with spinal anesthesia for degenerative lumbar spinal disorders in an 8
year period. Spinal anesthesia was performed at the L3-L4 or L4-L5 level and
subarachnoid block was achieved with 15 mg of 0.5% plain bupivacaine with 2 MUg
of fentanyl and 0.2 mg of epinephrine. There was no failure of anesthesia. The
patients were closely monitored for complications associated with the SA
technique and especially hypotension and bradycardia but no gross alterations in
cardiovascular stability were noted. RESULTS: Among the 497 patients, 139 were
male and 358 were female with a median age of 51 years. The average anesthesia
duration was 130 minutes and the average operative time was 85 minutes. In the
postoperative period 36 patients has nausea (7.2%) and 18 of them had vomiting
(3.6%) that required one dose of antiemetic. No spinal headache was observed and
36 (7.2%) patients complained of urinary retention. All recovered with urinary
cannulation within 24 hours. No respiratory complication occurred and no patient
died. CONCLUSION: Spinal anesthesia is a safe and effective procedure for the
lumbar spinal stabilization surgery, especially in high-riskpatients. Proper
precautions should be taken in order to achieve an effective anesthesia for these
operations.
PMID- 26442545
TI - Successful Transarterial Embolization of a Posttraumatic Fistula Between a
Posterior Communicating Artery Aneurysm and the Cavernous Sinus: A Case Report.
AB - Posterior communicating artery (PCoA) aneurysm-cavernous sinus fistulae are an
extremely rare complication of head injury . The treatment of PCoA aneurysm
cavernous sinus fistulae has not been well described. A 27-year-old man was
admitted with a retroocular bruit and blurred vision of the left eye seven months
after a severe head injury. We report the angiographic appearance of a posterior
communicating artery (PCoA) aneurysm with a fistula to the cavernous sinus. This
injury had been previously misinterpreted to be a PCoA aneurysm by computerized
tomographic angiography (CTA). The patient was successfully treated with coils
and Onyx of a fistula between the PCoA aneurysm and cavernous sinus.
PMID- 26442546
TI - Intracranial Extracranial Huge Meningioma: Report of a Case.
AB - Meningioma accounts for 15% to 20% of all intracranial neoplasms. Intracranial
meningioma is a common brain tumor but huge meningiomas with extracranial
extensions are extremely rare. Various symptoms, including neurological deficits
and epileptic seizures are very frequent in these cases. Surgery still remains
the principal form of the treatment and must be preceded by appropriate
preoperative diagnostics. We report an unusual case of a huge meningioma of the
brain (intracranial-extracranial extension) invading and destroying the skull
bone and subcutaneous and cutaneous tissue. A 44-year old man in otherwise good
general health was admitted to our University Neurosurgical Clinic. The MRI
revealed an intracranial-extracranial lesion invading the skull bone,
subcutaneous and cutaneous tissue. The tumour was removed by microsurgery. The
bone was found to be predominantly lytic, and dura was infiltrated by the tumor.
The bone and the dura were completely removed together with the entire tumor.
Such cases are very rarely seen these days because of modern radiology techniques
A giant intracranial-extracranial meningioma is therefore very unusual.
Radiotherapy is generally recommended for incompletely resected meningioma and
malignant meningioma.
PMID- 26442547
TI - Lhermitte-Duclos Disease Treated Surgically in an Elderly Patient: Case Report
and Literature Review.
AB - A 75-year-old man with Lhermitte-Duclos Disease (LDD) manifesting as progressive
headache is presented. Magnetic resonance imaging demonstrated a right cerebellar
mass lesion with the characteristic "tiger-striped appearance". A mild mass
effect was evident at the medulla oblongata, accompanied by inferior displacement
of the right cerebellar tonsil. Thus, tonsillar herniation was considered the
cause of his headache and he underwent partial resection of the tumor to solve
tonsillar herniation. His headache gradually improved. LDD in the elderly is
quite rare. Several differences in the nature of the lesion are seen in the
elderly, with tendencies toward a male predominance, hypervascularity, and low
rates of association with Cowden disease. Moreover, partial resection to reduce
mass effect can improve clinical symptoms without recurrence. In symptomatic LDD
in the elderly, to avoid surgical complication, we recommend partial resection to
reduce mass effect.
PMID- 26442548
TI - Hydranencephaly: Considering Prolonged Survival and Treatment by Endoscopic
Choroid Plexus Coagulation.
AB - Arachnoid collapse is a previously unreported complication of endoscopic choroid
plexus coagulation (ECPC) treatment of hydranencephaly and is demonstrated in
this case report. The variable anatomy found in hydranencephaly supports the use
of ECPC as the preferred treatment option. However, the same anatomical anomalies
predispose the procedure to this unique complication. A brief literature review
of hydranencephaly has also been performed and is reported through the
discussion. Neurosurgeons must be aware of this very dangerous complication and a
discussion of preventative measures are made. The use of ECPC and the clinical
expectations of treating patients with hydranencephaly is also discussed.
PMID- 26442549
TI - The Contribution of Three-Dimensional Computerized Tomographic Angiography in the
Head Positioning of the Patients with Middle Cerebral Artery Aneurysms.
AB - Surgical intervention is a gold standard technique for ruptured and unruptured
middle cerebral artery bifurcation aneurysm. Before surgical intervention it is
necessary to know the three-dimensional shape, surgical position, projection and
position of the aneurysm and the course of the parent artery. In a demonstrative
case with middle cerebral artery aneurysm, using the OsiriX MD image processing
software for DICOM images, it was demonstrated the position of the aneurysm neck,
the projection of the aneurysm and the course of the M1 segment in relation with
dynamic rotation and extension of the head. These dynamic videographic
neuroradiological images may enhance the surgical anatomic perspective of the
surgeon before the surgical intervention.
PMID- 26442550
TI - 5-Aminolevulinic Acid-Induced Fluorescence in Cerebellar Primary Central Nervous
System Lymphoma: A Case Report and Literature Review.
AB - 5-Aminolevulinic acid (5-ALA)-induced fluorescence-guided resection is a widely
used procedure for patients with malignant gliomas. However, the clinical
application of 5-ALA for surgery in primary central nervous system lymphoma
(PCNSL) is uncommon. Here, we present a case of PCNSL treated using 5-ALA-induced
fluorescence-guided resective surgery. A 70-year-old woman presented with
cerebellar ataxia, and magnetic resonance imaging revealed an irregularly shaped
and homogenously enhanced mass with surrounding brain edema in the vermis that
extended to the right hemisphere of the cerebellum. Under the preoperative
diagnosis of a malignant glioma in the cerebellum, the patient underwent 5-ALA
induced fluorescence-guided surgery. Under blue light illumination, the tumor
revealed strong 5-ALA-induced fluorescence. The tumor was identified as a diffuse
large B-cell lymphoma. After partial resection, the patient received adjuvant
chemotherapy and radiotherapy. Importantly, the neurological deficit of the
patient improved, and recurrence of the tumor was not observed 21 months post
surgery. Together with previous reports, this case study emphasizes the efficacy
of the surgical application of 5-ALA for PCNSL.
PMID- 26442551
TI - Solitary Metastasis of Renal Cell Carcinoma to the Third Ventricle Mimicking a
Colloid Cyst: Case Report.
AB - Colloid cysts are the most common third ventricle lesions and metastasis to this
area is rare. We presented a case of solitary metastasis from a renal cell
carcinoma to the third ventricle choroid plexus mimicking a colloid cyst. A 53
year-old man, who had a history of renal cell carcinoma 12 years ago, was
operated for single third ventricle lesion and hydrocephalus via a transcallosal
approach. Total removal could not be performed due to intraoperative massive
bleeding. Histological examination revealed a metastatic renal cell carcinoma.
The patient died on the postoperative 13th day because of bleeding from the
residual tumor. Stereotactic radiosurgery and ventriculoperitoneal shunting might
be favorable in such cases in order to avoid serious complications.
PMID- 26442552
TI - Massive Hemorrhage from the Posterior Ethmoidal Artery during Transsphenoidal
Surgery: Report of 2 Cases.
AB - Nasal bleeding is a major complication that can occur during and after
transsphenoidal surgery (TSS) for intra- and suprasellar tumors. In most cases,
the cause of this bleeding can be attributed to a branch of the maxillary artery
called the sphenopalatine artery, injury to which can lead to life-threatening
situations. Upon exposure of the suprasellar region and planum sphenoidale during
surgery, it is also important to avoid damaging the posterior ethmoidal artery
(PEA), a branch of the ophthalmic artery. While recent advancement in endoscopic
techniques enables the performance of extended TSS, the chances of PEA injury
seem to be increasing. In the current report, we present two cases that showed
massive PEA bleeding during regular (not extended) TSS. The total blood loss was
2280 ml and 2150 ml, and endoscopic views disturbed by the massive hemorrhages
remarkably delayed accurate stanching of the responsive artery. Therefore,
anatomical recognition of the PEA is required to avoid fatal hemorrhaging during
even regular TSS, especially for the beginners of this surgery.
PMID- 26442553
TI - Bilateral Internal Carotid Artery Occlusion as a Cause of Intraventricular
Hemorrhage due to Pial Collateral Vessels.
AB - In patients with high-grade atherosclerotic stenosis or occlusion of the
extracranial cerebral arteries, subarachnoid hemorrhage (SAH) may occur,
potentially due to rupture of fragile dilated pial collateral vessels. This
association has been well described in Moyamoya disease. There are only few cases
in the literature that reported SAH due to bilateral carotid artery stenosis but
intraventricular hemorrhage caused by dilated pial collateral has not been
reported yet. We present a case of bilateral carotid artery occlusion presented
with intraventricular hemorrhage. Based on the findings in the present case,
carotid artery stenosis or occlusion may present with intraventricular hemorrhage
due to rupture of the dilated, fragile collateral vessels.
PMID- 26442554
TI - Moyamoya Disease Associated with Recurrent Right Thalamic Haemorrhage and
Hydrocephalus: A Case Report.
AB - Moyamoya disease, a rare chronic, progressive cerebrovascular disease leads to
occlusion of intracranial internal carotid arteries and its proximal branches. We
report a case of a 51-year-old female who presented with recurrent thalamic bleed
and intraventricular haemorrhage nine years apart in the same territory. The
first bleed was managed conservatively and second bleed led to development of
hydrocephalus. The acute phase of the hydrocephalus was managed by external
ventricular drainage and the final CSF diversion was managed by
ventriculoperitoneal shunt. The definitive treatment could not be done to denial
of consent from the patient. We present the case to highlight the role CSF
diversion as a means of palliative treatment for the Moyamoya disease.
PMID- 26442555
TI - Bipartite Atlas with Os Odontoideum with Block Cervical Vertebrae: A Case Report
with Emphasis on the "Overlooked" C1 Lateral Masses.
AB - Though rare, a variety of bipartite atlas has been described. However, little has
been mentioned about the hypoplastic C1 lateral masses in these cases. An unusual
case of bipartite atlas, with hypoplastic lateral masses, os odontoideum and
block vertebrae has been described with the surgical challenges encountered. The
emphasis here is to study the C1 lateral masses and attempting C1-2 fusion before
resorting to occipito-cervical fusion. A 42-year-old lady presented with
progressive spastic quadriparesis. Radiology revealed blocked C2-5 vertebrae with
os odontoideum with atlanto-axial dislocation with bifid anterior arch of atlas,
hypoplastic C1 lateral masses (ill formed postero-inferior part) and posterior
arch. Magnetic resonance imaging showed cervicomedullary compression. Reduction
was achieved by opening the C1-2 joints posteriorly. Though bilateral C1-2
lateral mass fusion was attempted, we succeeded only on one side necessitating O
C2 fusion on the other. Patient improved neurologically, though neck movements
were restricted. Partially formed (peg shaped) lateral mass of C1 suggests its
development from more than one sclerotome. With normal superior facets of C1
lateral mass, an attempt should always be made at fusing the C1-2 joint rather
than O-C2 in such cases to preserve some neck movements.
PMID- 26442556
TI - Locally Aggressive De Novo Spinal Fibromatosis: Case Report and Review of the
Literature.
AB - Fibromatosis is a benign lesion, which originates from proliferating fibroblasts.
Although fibromatosis is a benign tumor, it is locally aggressive and invasive.
Spinal presentation of fibromatosis is very rare, and case reports are the only
source of the clinical knowledge. Herein, we describe the oldest patient having
spinal fibromatosis with de novo occurrence and aggressive nature. A 68-year-old
female patient admitted to our outpatient clinic with low back pain and
neurological claudication. On lumbar spine magnetic resonance imaging, she had
spinal canal stenosis with a concomitant lesion in the left longissimus muscle.
We did our best to resect the tumor, entirely. The pathology result was
consistent with spindle cell lesion. The lesion recurred 6 months after the
primary surgery. In the second surgery, we did en bloc resection. Pathology and
immunohistochemical analysis results were consistent with fibromatosis. After the
second surgery, she had adjuvant radiotherapy. There was nothing other than
radionecrosis in the operation site, still after 2 years. In conclusion,
radiological work-up is usually insufficient to make fibromatosis diagnosis and
whole pathological specimen should be carefully evaluated to achieve the accurate
diagnosis. Spinal fibromatosis is very rare and its treatment methods have not
universally been conceptualized. However, adjuvant therapies are necessary after
en bloc resection.
PMID- 26442557
TI - Lumbar Epidural Varicose Vein: Early Neurological Improvement and Late
Radiological Full Recovery with Surgery; The Importance of Magnetic Resonance
Imaging in Follow-Up.
AB - A lumbar epidural varicose vein is a rare clinical condition that can lead to
neurological deficits. 3 types of lumbar epidural varicose veins were described
according to the magnetic resonance imaging (MRI) findings: Type 1 is a
thrombosed dilated epidural vein, type 2 is a non-thrombosed dilated epidural
vein and type 3 is a sub-membraneous epidural hematoma. Enlarged epidural venous
plexuses must be decompressed if they have lead to a neurological deficit.
Surgical treatment is by excision or disrupting the cyst's integrity. We present
a case of lumbar epidural varicose vein that was surgically treated twice and
showed no radiological change despite the disruption of integrity with a partial
excision. The lesion spontaneously and completely disappeared in the late period.
We emphasize the importance of MRI in follow-up.
PMID- 26442558
TI - Hemorrhagic Epidermoid Cyst in Cerebellar Vermis.
AB - Intracranial epidermoid cysts are usually located in the paramedian regions with
characteristic imaging features. Intracystic hemorrhage is rarely reported with
most in the cerebellopontine angle area. We described a case of hemorrhagic
epidermoid cyst in cerebellar vermis. The patient was a 21-year-old male
presenting with a first episode of convulsive seizure attack as the initial and
sole symptom. Head computed tomography showed a mass lesion in the cerebellar
vermis with high density and nodular low density in the back of the lesion.
Magnetic resonance imaging revealed most of the lesion was hypointense to
isointense, extremely hypointensity on T1-, T2-weighted imaging respectively. The
nodule was hyperintense on both T1- and T2-weighted images. The atypical clinical
presentation, location and radiological features of intracranial epidermoid cyst
make accurate diagnosis quite challenging. In such cases, scrutinized
histopathological examination is necessary to exclude the malignancy that may
need radio/chemotherapy.
PMID- 26442559
TI - A Right Middle Cerebral Artery Infarct After Frontal Eosinophilic Granuloma
Resection in an 8-Year-Old Boy with Factor V Leiden.
AB - Stroke in children is relatively uncommon. We describe an 8-year-old boy
diagnosed with primary eosinophilic granuloma (EG) of the frontal bone. After
excision of the EG, the postoperative course was eventful. The patient had an
acute right middle cerebral artery (MCA) infarct and had been comatose with a
diminished Glasgow Coma Scale (GCS) score of 5. Urgent decompressive
hemicraniectomy with duraplasty was performed. The postoperative course after the
second operation was uneventful. Hematological tests revealed a diagnosis of
factor V Leiden. The patient was discharged with left hemiparesis and GCS of 15.
To the best of our knowledge, no such clinical picture of MCA infarction after EG
excision has been described before. Neurosurgeons should be aware of inherited
thrombophilias, such as factor V Leiden, if the postoperative clinical course
worsens because of cerebral artery thrombosis. Also, decompressive
hemicraniectomy could be life saving and should be performed urgently without any
hesitation.
PMID- 26442560
TI - Spontaneous Resolution of Bilateral Chronic Subdural Hematoma.
PMID- 26442561
TI - Climate adversity and resilience: the voice of rural Australia.
AB - INTRODUCTION: Over the past decade, Australia has experienced prolonged drought
and extensive flooding. It is argued that such events impact more significantly
on rural communities than urban. Although there is a body of research
investigating the effects of drought on mental and physical health in rural
Australia, little research has examined the effects of flood and drought on
wellbeing. This article explores the influence of drought and flood on the
wellbeing of rural residents in New South Wales (NSW), Australia. METHODS: Forty
six individuals living in four rural communities in NSW were recruited and asked
their experience of flood and drought using in-depth semi-structured face to face
interviews or focus groups. The study used a grounded hermeneutic approach to
contextualise participants' experiences within a rural social and cultural
construct. RESULTS: Weather was found to be at the core of rural life, with flood
and drought contributing to decreased wellbeing from stress, anxiety, loss and
fear. Social connectedness was found to promote resilience in rural communities
buffering the effects of flood and drought. CONCLUSIONS: Flood and drought have
negative impacts on an individual's wellbeing. Although these negative effects
were seen to be buffered by individual and community resilience, the long term
emotional impact of flood and drought on rural communities needs to be further
considered.
PMID- 26442562
TI - Does skill retention benefit from retentivity and symbolic rehearsal? - two
studies with a simulated process control task.
AB - Two experiments were designed to compare two symbolic rehearsal refresher
interventions (imaginary practice, a hidden introspective process) and
investigate the role of retentivity in skill retention. Retentivity is
investigated as the ability to memorise and reproduce information and
associations that were learned a short time ago. Both experiments comprised
initial training (week 1), a symbolic rehearsal for the experimental group (week
2) and a retention assessment (week 3). In the first study, the experimental
group received a symbolic rehearsal, while the control group received no
rehearsal. In the second study, the experimental group received the same symbolic
rehearsal used in study 1, enhanced with rehearsal tasks addressing human
computer interaction. The results showed that both symbolic rehearsal
interventions were equally likely to mitigate skill decay. The retentivity showed
medium to high correlations with skill retention in both studies, and the results
suggest that subjects high in retentivity benefit more from a symbolic rehearsal
refresher intervention. Practitioner Summary: Skill decay becomes a problem in
situations in which jobs require the correct mastery of non-routine situations.
Two experimental studies with simulated process control tasks showed that
symbolic rehearsal and retentivity can significantly mitigate skill decay and
that subjects higher in retentivity benefit more from refresher interventions.
PMID- 26442563
TI - Linking emotional distress to unhealthy sleep duration: analysis of the 2009
National Health Interview Survey.
AB - OBJECTIVE: The objective of the study was to examine the independent association
of emotional distress with unhealthy sleep duration (defined as <7 or >8 hours).
METHODS: Data from the 2009 National Health Interview Survey (NHIS), a cross
sectional household survey, were analyzed to investigate the associations of
emotional distress with unhealthy sleep durations, adjusting for sociodemographic
factors, health risks, and chronic diseases through hierarchical multiple
logistic regression analysis. PARTICIPANTS: A total of 27,731 participants (age
range 18-85 years) from the NHIS 2009 dataset were interviewed. MEASURES:
Unhealthy sleep duration is defined as sleep duration <7 or >8 hours, whereas
healthy sleep is defined as sleep duration lasting for 7-8 hours. Emotional
distress is based on the Kessler 6 Non-Specific Distress Battery, which assesses
the frequency of feeling sad, nervous, restless, hopeless, worthless, and
burdened, over a 30-day period. RESULTS: Of the sample, 51.7% were female; 83.1%
were white and 16.9% were black. Eleven percent experienced emotional distress
and 37.6% reported unhealthy sleep. Adjusted logistic regression analysis
revealed that individuals with emotional distress had 55% greater odds of
reporting unhealthy sleep (odds ratio [OR] =1.55, 95% confidence interval [CI]
=1.42, 1.68, P<0.001). CONCLUSION: Emotional distress, an important proxy for
poor psychological health, was a significant predictor of unhealthy sleep,
independent of the influences of several factors including demographic (age,
education, sex, race/ethnicity, and family income), health risks (alcohol
consumption and smoking status), and chronic diseases/conditions (diabetes,
obesity, hypertension, heart disease, cancer, and arthritis).
PMID- 26442564
TI - Prior stillbirth is a risk factor for stillbirth in a subsequent pregnancy.
PMID- 26442565
TI - Routine iron supplementation for non-anaemic pregnant women in developed
countries needs evaluation.
PMID- 26442566
TI - Risk of new-onset diabetes with statin use should not be overemphasised.
PMID- 26442567
TI - Sugar-sweetened beverage consumption is linked to global adult morbidity and
mortality through diabetes mellitus, cardiovascular disease and adiposity-related
cancers.
PMID- 26442568
TI - Nucleotide diversity patterns of three divergent soybean populations: evidences
for population-dependent linkage disequilibrium and taxonomic status of Glycine
gracilis.
AB - The level of linkage disequilibrium (LD) is a major factor to determine DNA
polymorphism pattern of a population and to construct high-resolution maps useful
in localizing and gene cloning of complicated traits. Here, we investigated LD
level of three soybean populations with different genetic backgrounds and
taxonomic status of G. gracilis by comparing the DNA polymorphism patterns of
four high-diversity single-copy nuclear genes. A total of 152, 22, and 77
accessions of G. soja, G. gracilis, and G. max were observed. The results
indicated that G. max retained only 75.3 (pi) and 39% (theta) of the nucleotide
polymorphism found in G. soja. Four gene loci evolved according to neutrality in
both G. max and G. gracilis populations, and three gene loci evolved according to
neutrality in G. soja population by Tajima's and Fu and Li's test. However, one
gene locus deviated from neutrality by Fu and Li's test in the G. soja
population. Further, medial level of LD (average r (2) = 0.2426) was found in
intragene in G. max and G. gracilis populations, but unexpected low level of LD
(r (2) <= 0.0539) was found in G. soja population. Significant genetic
differentiation was detected between G. max and G. soja populations and also
between G. max and G. gracilis populations; however, nonsignificant genetic
differentiation was found between G. gracilis and G. soja populations. The
results suggest that LD level depends on genetic background of soybean
population, and implicit that G. gracilis should be regarded as the variant of G.
soja, not as an independent species.
PMID- 26442569
TI - Old relief printing applied to the current preparation of multi-color and high
resolution colloidal photonic crystal patterns.
AB - Monodisperse SiO2 colloids are assembled into colloidal crystals in the mixture
of monomer and solvent, which is transformed into a mechanochromic photonic
crystal paper by polymerization. Following the relief printing strategy, the
printing plates are pressed onto the paper to generate letters or images due to
the contrast of structural color between the deformed and the undeformed paper,
and the images can be permanently retained through UV curing. The wide tunable
range of structural color for the current paper under deformation helps to
realize multi-color printing. The localized deformation among or even inside the
colloidal microcrystals renders the paper with a precise mechanochromic response
to the printing plates and leads to the production of high resolution photonic
crystal patterns.
PMID- 26442571
TI - Synthesis and crystal structure of a new hexagonal perovskite 7H
Ba7Li1.75Mn3.5O15.75 with Mn(4+)/Mn(5+) charge distribution.
AB - Ba7Li1.75Mn3.5O15.75 is a new hexagonal perovskite whose crystal structure has
elements typical for the layered hexagonal perovskites and quasi-one-dimensional
oxides, hence representing a new polytype. It has been synthesized via a solid
state microwave route. The crystal structure was solved using a combination of X
ray and neutron diffraction data, which show that Ba7Li1.75Mn3.5O15.75
crystallizes in a hexagonal unit cell with parameters a = 5.66274(2) A and c =
16.7467(1) A (V = 465.063(4) A(3)), with one formula unit, and can be described
as columns of face-shared octahedra occupied by Mn(4+) and Li(+) cations and
vacancies along the c axis separated in the ab plane by barium atoms. Every sixth
layer, the coordination of Mn(5+) and Li(+) changes to tetrahedral. Additional
local ordering of manganese and lithium atoms among cationic sites leading to the
formation of a rhombohedral supercell has been observed by scanning transmission
electron microscopy.
PMID- 26442572
TI - A triple-amplification colorimetric assay for antibiotics based on magnetic
aptamer-enzyme co-immobilized platinum nanoprobes and exonuclease-assisted target
recycling.
AB - Herein, an ultrasensitive and selective colorimetric assay for antibiotics, using
chloramphenicol (CAP) as the model analyte, was developed based on magnetic
aptamer-HRP-platinum composite probes and exonuclease-assisted target recycling.
The composite probes were prepared through immunoreactions between the double
stranded DNA antibody (anti-DNA) labeled on core-shell Fe3O4@Au nanoparticles
(AuMNP-anti-DNA) as the capture probe, and the double stranded aptamer (aptamer
hybrid with its complementary oligonucleotides) labeled on Pt@HRP nanoparticles
as the nanotracer (ds-Apt-HRP-PtNPs). When the CAP samples were incubated with
the probes for 30 min at room temperature, they could be captured by the aptamer
to form a nanotracer-CAP complex, which was then released into the supernatant
after magnetic separation. This is because the anti-DNA on the capture probes
cannot recognize the single strand aptamer-CAP complex. The exonuclease I (Exo I)
added into the supernatant can further digest the aptamer-CAP from the 3'-end of
the aptamer and the CAP in the aptamer-CAP complex can be released again, which
can further participate in a new cycling process to react with the probes. Pt and
HRP in the nanotracer could both catalyze and dual amplify the absorbance at 650
nm ascribed to the 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2 system. Moreover,
Exo I can assist the target recycling, which can further amplify the signal.
Thus, the triple amplified signal can be quantified by ultraviolet-visible
spectroscopy. The experimental results showed that the CAP detection possessed a
linear range of 0.001-10 ng mL(-1) and a detection limit of 0.0003 ng mL(-1) (S/N
= 3). The assay was successfully employed to detect CAP in milk, which is much
more facile, time saving, and sensitive than the commercial ELISA kits.
PMID- 26442573
TI - Spatiotemporal characteristics of organic contaminant concentrations and
ecological risk assessment in the Songhua River, China.
AB - To control source pollution and improve water quality, an understanding of the
spatiotemporal characteristics of organic contaminant concentrations in affected
receiving waters is necessary. The Songhua River in northeast China is the
country's third-largest domestic river and loadings of organic contaminants along
an industrialized section have made it the focal point of a national pollution
reduction plan. In addition to water quality issues, management of the Songhua
River basin must also address local economic development, aquatic ecosystem
sustainability and political relationships with Russia. In three periods spanning
2006 to 2010, eight polycyclic aromatic hydrocarbons (PAHs) and eight phenols
were measured in surface waters at ten monitoring sites along the river. A
generalized linear model (GLM) was used to characterize water quality at
different sites and time periods. Chemical concentrations of the organic
compounds showed significant sinusoidal seasonal patterns and the concentrations
declined significantly from 2006 to 2010, possibly due to management practices
designed to control water pollution. A critical body residue analysis showed that
water concentrations measured during the winter of 2007 across all monitoring
sites, but especially at S1-Shaokou and S2-Songhuajiangcun, presented a high risk
for fish species. The spatiotemporal characteristics of water quality and
estimated ecological risks shown here add to the body of knowledge to develop
policies on industrial output and pollution management strategies for the Songhua
River basin.
PMID- 26442574
TI - Metallic nanoparticle shape and size effects on aluminum oxide-induced
enhancement of exciton-plasmon coupling and quantum dot emission.
AB - We investigate the shape and size effects of gold metallic nanoparticles on the
enhancement of exciton-plasmon coupling and emission of semiconductor quantum
dots induced via the simultaneous impact of metal-oxide and plasmonic effects.
This enhancement occurs when metallic nanoparticle arrays are separated from the
quantum dots by a layered thin film consisting of a high index dielectric
material (silicon) and aluminum oxide. Our results show that adding the aluminum
oxide layer can increase the degree of polarization of quantum dot emission
induced by metallic nanorods by nearly two times, when these nanorods have large
aspect ratios. We show when the aspect ratio of these nanorods is reduced to
half, the aluminum oxide loses its impact, leading to no improvement in the
degree of polarization. These results suggest that a silicon/aluminum oxide layer
can significantly enhance exciton-plasmon coupling when quantum dots are in the
vicinity of metallic nanoantennas with high aspect ratios.
PMID- 26442575
TI - Comparative net cost impact of the utilization of panitumumab versus cetuximab
for the treatment of patients with metastatic colorectal cancer in Canada.
AB - OBJECTIVE: Clinical practice guidelines support the use of the epidermal growth
factor receptor (EGFR) inhibitors panitumumab and cetuximab for the treatment of
metastatic colorectal cancer (mCRC) after failure of other chemotherapy regimens,
based on significant clinical benefits in patients with wild-type KRAS. The
purpose of the analysis was to compare provincial hospital costs when using
panitumumab vs cetuximab with or without irinotecan in this patient population
using a Net Impact Analysis (NIA) approach. METHODS: The NIA determined the total
per patient cost of the reimbursed regimens of panitumumab vs cetuximab in
British Columbia, Alberta, Manitoba, Ontario, and Quebec. Utilization of
healthcare resources related to EGFR inhibitor infusions, follow-up monitoring,
and treatment of adverse events (AEs) were also included. Healthcare resource use
including drugs, medical supplies, laboratory testing, oncology infusion time,
and healthcare professionals' time was obtained through expert consultation and
the use was then multiplied by the province-specific cost of each resource.
Numerous sensitivity analyses were conducted. RESULTS: Based on the dosing
regimens in place in each province, the total annual per patient cost of
panitumumab ranged from $22,203-$32,600, while the total annual per patient cost
of cetuximab treatment varied from $30,321-$40,908. Treatment with panitumumab
resulted in lower costs in all cost categories including drug acquisition,
infusion preparation/administration, patient monitoring, and AE management. Per
patient savings with panitumumab ranged from a low of $3815 in British Columbia
to a high of $10,603 in Ontario. In sensitivity analyses, panitumumab remained
cost saving in all scenarios where the savings ranged from $150-$16,006 per
patient. CONCLUSIONS: Treating chemorefractory mCRC patients with panitumumab
rather than cetuximab reduced healthcare resource costs. Provincial healthcare
savings achieved with the use of panitumumab could potentially be re-allocated to
other cancer treatments, although further study would be needed to validate this
assumption.
PMID- 26442576
TI - Chain Length of Free Fatty Acids Influences the Phase Behavior of Stratum Corneum
Model Membranes.
AB - The skin, the largest organ of the human body, forms a flexible interface between
our internal and external environment that protects our organism from exogenous
compounds as well as excessive water loss. The stratum corneum (SC), the
outermost layer of mammal epidermis, is mainly responsible for the skin
impermeability. The SC is formed by corneocytes embedded in a lipid matrix, which
is mostly constituted of ceramides (Cer), free fatty acids (FFA), and cholesterol
(Chol), organized in two coexisting crystalline lamellar phases. This arrangement
of lipids is crucial to skin barrier function. The aim of this paper is to
determine the impact of FFA chain length on the phase behavior of SC model lipid
membranes using solid-state deuterium NMR and IR spectroscopy. We studied ternary
mixtures of N-lignoceroyl-d-erythro-sphingosine (Cer24), cholesterol, and
palmitic (FFA16) or lignoceric (FFA24) acid in an equimolar ratio. This
proportion replicates the lipid composition found in the SC lipid matrix. Our
studies revealed that the phase behavior of Cer24/FFA/Chol ternary mixtures is
strongly affected by the length of the FFA. We found the formation of phase
separated crystalline lipid domains when using palmitic acid whereas the use of
lignoceric acid results in a more homogeneous mixture. In addition, it was
observed that mixtures with lignoceric acid form a gel phase, a very unusual
feature for SC model mixtures.
PMID- 26442577
TI - Computational biomechanics of human brain with and without the inclusion of the
body under different blast orientation.
AB - Three different human head models in a free space are exposed to blast waves
coming from four different directions. The four head-neck-body models composed of
model a, with the neck free in space; model b, with neck fixed at the bottom; and
model c, with the neck attached to the body. The results show that the effect of
the body can be ignored for the first milliseconds of the head-blast wave
interactions. Also one can see that although most biomechanical responses of the
brain have similar patterns in all models, the shear stresses are heavily
increased after a few milliseconds in model b in which the head motion is
obstructed by the fixed-neck boundary conditions. The free-floating head model
results are closer to the attached-body model.
PMID- 26442578
TI - Neuroanatomical correlates of individual differences in social anxiety in a non
clinical population.
AB - Socially anxious individuals are characterized as those with distorted negative
self-beliefs (NSBs), which are thought to enhance reactions of social distress
(emotional reactivity) and social avoidance (social functioning). However, it
remains unclear whether individual differences in social distress and social
avoidance are represented by differences in brain morphometry. To probe into
these neural correlates, we analyzed magnetic resonance images of a sample of 130
healthy subjects and used the Connectome Computation System (CCS) to evaluate
these factors. The results showed that social distress was correlated with the
cortical volume of the right orbitofrontal cortex (OFC) and the subcortical
volume of the left amygdala, while social avoidance was correlated with the
cortical volume of the right dorsolateral prefrontal cortex (DLPFC).
Additionally, loneliness might mediate the relationship between the amygdala
volume and the social distress score. Our results demonstrated that social
distress and social avoidance were represented by segregated cortical regions in
the healthy individuals. These findings might provide a valuable basis for
understanding the stable brain structures underlying individual differences in
social anxiety.
PMID- 26442579
TI - Introducing Journal Sections.
PMID- 26442580
TI - A Possible Association Between Thyroid Cancer and Breast Cancer.
AB - BACKGROUND: Several lines of evidence suggest that breast cancer (BC) and thyroid
cancer (TC) occur together in the same female patients more frequently than would
be expected by chance. This study investigated the prevalence and
clinicopathological characteristics of second primary BC in TC patients and
second primary TC in BC patients. METHODS: A retrospective case-controlled study
was performed in 4243 patients with differentiated TC and 6833 patients with BC.
Age-matched control groups without second malignancies were selected. RESULTS: Of
the 4243 patients with TC, 55 patients developed subsequent BC during a five-year
follow-up (range 2-40 years); the standardized incidence ratio (SIR) was 2.45
[confidence interval (CI) 1.83-2.96]. Among the 6833 patients with BC, 81
patients developed subsequent TC during a 6.2-year follow-up (range 2-40 years);
the SIR was 2.18 [CI 1.43-2.82]. Subsequent second BC or TC diagnosed within five
years of the initial primary malignancy showed more clinical characteristics
consistent with early-stage cancer than did control BC or TC patients. Notably,
the expression of both the estrogen and progesterone receptors was significantly
higher in the tissues of BC patients with coexisting TC compared with those with
BC alone. CONCLUSIONS: The overall risk of second primary TC or BC is increased
in patients with prior BC or TC, respectively. The early detection of second
cancer might have contributed to these findings. However, BC that coexisted with
TC had a higher expression of hormone receptors, suggesting an association
between the molecular pathogenesis of TC and BC.
PMID- 26442581
TI - James Cook University's rurally orientated medical school selection process:
quality graduates and positive workforce outcomes.
AB - INTRODUCTION: The regionally based James Cook University (JCU) College of
Medicine and Dentistry aims to meet its mission to address the health needs of
the region by using a selection policy favouring rural origin applicants and
providing students with early and repeated exposure to rural experiences during
training. This study seeks to determine if the JCU medical school's policy of
preferentially selecting rural and remote background students is associated with
differing patterns of undergraduate performance or graduate practice location.
METHODS: Data at application to medical school and during the undergraduate years
was retrieved from administrative databases held by the university and the
medical school. Postgraduate location data were obtained either from personal
contact via email, telephone or Facebook or electronically from the Australian
Health Practitioner Regulation Authority website. Practice location was described
across Australian Standard Geographical Classification Remoteness Area (ASGC-RA)
categories, with 1 being a major city and 5 being a very remote location.
RESULTS: The 856 Australian-based students accepted into the JCU medical program
between 2000 and 2008 came from all geographical regions across Australia: 20%
metropolitan (ASGC-RA 1), 20% inner regional (ASGC-RA 2), 56% outer regional
(ASGC-RA 3), and 5% from remote or very remote locations (ASGC-RA 4 and 5).
Having a rural or remote hometown at application (ASGC-RA 3-5) was significantly
associated with a lower tertiary entrance score (p<0.001), a lower interview
score in the medical school selection process (p<0.001), being less likely to be
admitted into the Honours program (p=0.001), being an advanced standing student
(p=0.025), being awarded a Medical Rural Bonded Scholarship (p=0.005), taking
longer to complete the 6-year course (p=<0.009) and having a lower academic
achievement across years 1 to 3 (p=0.002, p=0.005 and p=0.025, respectively).
Graduates having either a rural or a remote home town at application were more
likely to practise in rural (RA 3-5) towns than graduates from metropolitan/inner
regional centre across all postgraduate years. For example, the prevalence odds
ratios (POR) for graduates practising in a rural town at postgraduate year 1 (PGY
1) having either a rural or remote hometown were 2.6 and 1.8, respectively, times
that of graduates having a metropolitan/inner regional hometown, while at PGY 9
the PORs had increased to 4.2 and 9.5, respectively. Bonded medical place
students showed many similar trends to rural students in both their pre-medical
school and undergraduate performance indicators but lower engagement in rural
practice in the 5 years of data available. CONCLUSIONS: Some significant
differences were noted between rural and remote origin students and metropolitan
or inner regional origin students in terms of academic achievement in the first 3
years of the course and length of time taken to complete the course. However,
this group of rural and remote-origin students seems to do just as well in the
exams in the clinical years (years 4-6) and are much more likely to practise in
rural and remote areas. These data suggest that JCU's selection process favouring
rural origin applicants does not compromise academic standards, but does produce
graduates whose patterns of practice accord with the mission of the school.
PMID- 26442582
TI - Conspicuous male coloration impairs survival against avian predators in Aegean
wall lizards, Podarcis erhardii.
AB - Animal coloration is strikingly diverse in nature. Within-species color variation
can arise through local adaptation for camouflage, sexual dimorphism and
conspicuous sexual signals, which often have conflicting effects on survival.
Here, we tested whether color variation between two island populations of Aegean
wall lizards (Podarcis erhardii) is due to sexual dimorphism and differential
survival of individuals varying in appearance. On both islands, we measured
attack rates by wild avian predators on clay models matching the coloration of
real male and female P. erhardii from each island population, modeled to avian
predator vision. Avian predator attack rates differed among model treatments,
although only on one island. Male-colored models, which were more conspicuous
against their experimental backgrounds to avian predators, were accordingly
detected and attacked more frequently by birds than less conspicuous female
colored models. This suggests that female coloration has evolved primarily under
selection for camouflage, whereas sexually competing males exhibit costly
conspicuous coloration. Unexpectedly, there was no difference in avian attack
frequency between local and non-local model types. This may have arisen if the
models did not resemble lizard coloration with sufficient precision, or if real
lizards behaviorally choose backgrounds that improve camouflage. Overall, these
results show that sexually dimorphic coloration can affect the risk of predator
attacks, indicating that color variation within a species can be caused by
interactions between natural and sexual selection. However, more work is needed
to determine how these findings depend on the island environment that each
population inhabits.
PMID- 26442583
TI - Mitogen-activated Protein Kinase (MAPK) Activated by Prostaglandin E2
Phosphorylates Connexin 43 and Closes Osteocytic Hemichannels in Response to
Continuous Flow Shear Stress.
AB - Cx43 hemichannels serve as a portal for the release of prostaglandins, a critical
process in mediating biological responses of mechanical loading on bone formation
and remodeling. We have previously observed that fluid flow shear stress (FFSS)
opens hemichannels; however, sustained FFSS results in hemichannel closure, as
continuous opening of hemichannels is detrimental to cell viability and bone
remodeling. However, the mechanism that regulates the closure of the hemichannels
is unknown. Here, we show that activation of p44/42 ERK upon continuous FFSS
leads to Cx43 phosphorylation at Ser(279)-Ser(282), sites known to be
phosphorylated sites by p44/42 MAPK. Incubation of osteocytic MLO-Y4 cells with
conditioned media (CM) collected after continuous FFSS increased MAPK-dependent
phosphorylation of Cx43. CM treatment inhibited hemichannel opening and this
inhibition was reversed when cells were pretreated with the MAPK pathway
inhibitor. We found that prostaglandin E2 (PGE2) accumulates in the CM in a time
dependent manner. Treatment with PGE2 increased phospho-p44/42 ERK levels and
also Cx43 phosphorylation at Ser(279)-Ser(282) sites. Depletion of PGE2 from CM,
and pre-treatment with a p44/42 ERK pathway-specific inhibitor, resulted in a
complete inhibition of ERK-dependent Cx43 phosphorylation and attenuated the
inhibition of hemichannels by CM and PGE2. Consistently, the opening of
hemichannels by FFSS was blocked by PGE2 and CM and this blockage was reversed by
U0126 and the CM depleted of PGE2. A similar observation was also obtained in
isolated primary osteocytes. Together, results from this study suggest that
extracellular PGE2 accumulated after continuous FFSS is responsible for
activation of p44/42 ERK signaling and subsequently, direct Cx43 phosphorylation
by activated ERK leads to hemichannel closure.
PMID- 26442584
TI - Cell Cycle-dependent Changes in Localization and Phosphorylation of the Plasma
Membrane Kv2.1 K+ Channel Impact Endoplasmic Reticulum Membrane Contact Sites in
COS-1 Cells.
AB - The plasma membrane (PM) comprises distinct subcellular domains with diverse
functions that need to be dynamically coordinated with intracellular events, one
of the most impactful being mitosis. The Kv2.1 voltage-gated potassium channel is
conditionally localized to large PM clusters that represent specialized
PM:endoplasmic reticulum membrane contact sites (PM:ER MCS), and overexpression
of Kv2.1 induces more exuberant PM:ER MCS in neurons and in certain heterologous
cell types. Localization of Kv2.1 at these contact sites is dynamically regulated
by changes in phosphorylation at one or more sites located on its large
cytoplasmic C terminus. Here, we show that Kv2.1 expressed in COS-1 cells
undergoes dramatic cell cycle-dependent changes in its PM localization, having
diffuse localization in interphase cells, and robust clustering during M phase.
The mitosis-specific clusters of Kv2.1 are localized to PM:ER MCS, and M phase
clustering of Kv2.1 induces more extensive PM:ER MCS. These cell cycle-dependent
changes in Kv2.1 localization and the induction of PM:ER MCS are accompanied by
increased mitotic Kv2.1 phosphorylation at several C-terminal phosphorylation
sites. Phosphorylation of exogenously expressed Kv2.1 is significantly increased
upon metaphase arrest in COS-1 and CHO cells, and in a pancreatic beta cell line
that express endogenous Kv2.1. The M phase clustering of Kv2.1 at PM:ER MCS in
COS-1 cells requires the same C-terminal targeting motif needed for conditional
Kv2.1 clustering in neurons. The cell cycle-dependent changes in localization and
phosphorylation of Kv2.1 were not accompanied by changes in the
electrophysiological properties of Kv2.1 expressed in CHO cells. Together, these
results provide novel insights into the cell cycle-dependent changes in PM
protein localization and phosphorylation.
PMID- 26442585
TI - A Novel Retinoblastoma Protein (RB) E3 Ubiquitin Ligase (NRBE3) Promotes RB
Degradation and Is Transcriptionally Regulated by E2F1 Transcription Factor.
AB - Retinoblastoma protein (RB) plays critical roles in tumor suppression and is
degraded through the proteasomal pathway. However, E3 ubiquitin ligases
responsible for proteasome-mediated degradation of RB are largely unknown. Here
we characterize a novel RB E3 ubiquitin ligase (NRBE3) that binds RB and promotes
RB degradation. NRBE3 contains an LXCXE motif and bound RB in vitro. NRBE3
interacted with RB in cells when proteasome activity was inhibited. NRBE3
promoted RB ubiquitination and degradation via the ubiquitin-proteasome pathway.
Importantly, purified NRBE3 ubiquitinated recombinant RB in vitro, and a U-box
was identified as essential for its E3 activity. Surprisingly, NRBE3 was
transcriptionally activated by E2F1/DP1. Consequently, NRBE3 affected the cell
cycle by promoting G1/S transition. Moreover, NRBE3 was up-regulated in breast
cancer tissues. Taken together, we identified NRBE3 as a novel ubiquitin E3
ligase for RB that might play a role as a potential oncoprotein in human cancers.
PMID- 26442586
TI - Degradation of Stop Codon Read-through Mutant Proteins via the Ubiquitin
Proteasome System Causes Hereditary Disorders.
AB - During translation, stop codon read-through occasionally happens when the stop
codon is misread, skipped, or mutated, resulting in the production of aberrant
proteins with C-terminal extension. These extended proteins are potentially
deleterious, but their regulation is poorly understood. Here we show in vitro and
in vivo evidence that mouse cFLIP-L with a 46-amino acid extension encoded by a
read-through mutant gene is rapidly degraded by the ubiquitin-proteasome system,
causing hepatocyte apoptosis during embryogenesis. The extended peptide interacts
with an E3 ubiquitin ligase, TRIM21, to induce ubiquitylation of the mutant
protein. In humans, 20 read-through mutations are related to hereditary
disorders, and extended peptides found in human PNPO and HSD3B2 similarly
destabilize these proteins, involving TRIM21 for PNPO degradation. Our findings
indicate that degradation of aberrant proteins with C-terminal extension encoded
by read-through mutant genes is a mechanism for loss of function resulting in
hereditary disorders.
PMID- 26442587
TI - The Thermotolerant Yeast Kluyveromyces marxianus Is a Useful Organism for
Structural and Biochemical Studies of Autophagy.
AB - Autophagy is a conserved degradation process in which autophagosomes are
generated by cooperative actions of multiple autophagy-related (Atg) proteins.
Previous studies using the model yeast Saccharomyces cerevisiae have provided
various insights into the molecular basis of autophagy; however, because of the
modest stability of several Atg proteins, structural and biochemical studies have
been limited to a subset of Atg proteins, preventing us from understanding how
multiple Atg proteins function cooperatively in autophagosome formation. With the
goal of expanding the scope of autophagy research, we sought to identify a novel
organism with stable Atg proteins that would be advantageous for in vitro
analyses. Thus, we focused on a newly isolated thermotolerant yeast strain,
Kluyveromyces marxianus DMKU3-1042, to utilize as a novel system elucidating
autophagy. We developed experimental methods to monitor autophagy in K. marxianus
cells, identified the complete set of K. marxianus Atg homologs, and confirmed
that each Atg homolog is engaged in autophagosome formation. Biochemical and
bioinformatic analyses revealed that recombinant K. marxianus Atg proteins have
superior thermostability and solubility as compared with S. cerevisiae Atg
proteins, probably due to the shorter primary sequences of KmAtg proteins.
Furthermore, bioinformatic analyses showed that more than half of K. marxianus
open reading frames are relatively short in length. These features make K.
marxianus proteins broadly applicable as tools for structural and biochemical
studies, not only in the autophagy field but also in other fields.
PMID- 26442588
TI - Tumor Suppressive Function of p21-activated Kinase 6 in Hepatocellular Carcinoma.
AB - Our previous studies identified the oncogenic role of p21-activated kinase 1
(PAK1) in hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC).
Contrarily, PAK6 was found to predict a favorable prognosis in RCC patients.
Nevertheless, the ambiguous tumor suppressive function of PAK6 in
hepatocarcinogenesis remains obscure. Herein, decreased PAK6 expression was found
to be associated with tumor node metastasis stage progression and unfavorable
overall survival in HCC patients. Additionally, overexpression and silence of
PAK6 experiments showed that PAK6 inhibited xenografted tumor growth in vivo, and
restricted cell proliferation, colony formation, migration, and invasion and
promoted cell apoptosis and anoikis in vitro. Moreover, overexpression of kinase
dead and nuclear localization signal deletion mutants of PAK6 experiments
indicated the tumor suppressive function of PAK6 was partially dependent on its
kinase activity and nuclear translocation. Furthermore, gain or loss of function
in polycomb repressive complex 2 (PRC2) components, including EZH2, SUZ12, and
EED, elucidated epigenetic control of H3K27me3-arbitrated PAK6 down-regulation in
hepatoma cells. More importantly, negative correlation between PAK6 and EZH2
expression was observed in hepatoma tissues from HCC patients. These data
identified the tumor suppressive role and potential underlying mechanism of PAK6
in hepatocarcinogenesis.
PMID- 26442589
TI - Assembly of a Tyr122 Hydrophobic Cluster in Sarcoplasmic Reticulum Ca2+-ATPase
Synchronizes Ca2+ Affinity Reduction and Release with Phosphoenzyme
Isomerization.
AB - The mechanism whereby events in and around the catalytic site/head of Ca(2+)
ATPase effect Ca(2+) release to the lumen from the transmembrane helices remains
elusive. We developed a method to determine deoccluded bound Ca(2+) by taking
advantage of its rapid occlusion upon formation of E1PCa2 and of stabilization
afforded by a high concentration of Ca(2+). The assay is applicable to minute
amounts of Ca(2+)-ATPase expressed in COS-1 cells. It was validated by measuring
the Ca(2+) binding properties of unphosphorylated Ca(2+)-ATPase. The method was
then applied to the isomerization of the phosphorylated intermediate associated
with the Ca(2+) release process E1PCa2 -> E2PCa2 -> E2P + 2Ca(2+). In the wild
type, Ca(2+) release occurs concomitantly with EP isomerization fitting with rate
limiting isomerization (E1PCa2 -> E2PCa2) followed by very rapid Ca(2+) release.
In contrast, with alanine mutants of Leu(119) and Tyr(122) on the cytoplasmic
part of the second transmembrane helix (M2) and Ile(179) on the A domain, Ca(2+)
release in 10 MUm Ca(2+) lags EP isomerization, indicating the presence of a
transient E2P state with bound Ca(2+). The results suggest that these residues
function in Ca(2+) affinity reduction in E2P, likely via a structural
rearrangement at the cytoplasmic part of M2 and a resulting association with the
A and P domains, therefore leading to Ca(2+) release.
PMID- 26442591
TI - Recent advances in the application of total scattering methods to functional
materials.
AB - In this Feature Article we provide a description of some of the most recent
results obtained in the field of materials science by means of total scattering
methods and PDF analysis. Particular attention is devoted to the application of
PDF to functional materials and to examples showing the combination of PDF with
other solid state chemistry techniques.
PMID- 26442590
TI - Dopamine Transporter Activity Is Modulated by alpha-Synuclein.
AB - The duration and strength of the dopaminergic signal are regulated by the
dopamine transporter (DAT). Drug addiction and neurodegenerative and
neuropsychiatric diseases have all been associated with altered DAT activity. The
membrane localization and the activity of DAT are regulated by a number of
intracellular proteins. alpha-Synuclein, a protein partner of DAT, is implicated
in neurodegenerative disease and drug addiction. Little is known about the
regulatory mechanisms of the interaction between DAT and alpha-synuclein, the
cellular location of this interaction, and the functional consequences of this
interaction on the basal, amphetamine-induced DAT-mediated dopamine efflux, and
membrane microdomain distribution of the transporter. Here, we found that the
majority of DAT.alpha-synuclein protein complexes are found at the plasma
membrane of dopaminergic neurons or mammalian cells and that the amphetamine
mediated increase in DAT activity enhances the association of these proteins at
the plasma membrane. Further examination of the interaction of DAT and alpha
synuclein revealed a transient interaction between these two proteins at the
plasma membrane. Additionally, we found DAT-induced membrane depolarization
enhances plasma membrane localization of alpha-synuclein, which in turn increases
dopamine efflux and enhances DAT localization in cholesterol-rich membrane
microdomains.
PMID- 26442593
TI - Uncoating Mechanism of Carnation Mottle Virus Revealed by Cryo-EM Single Particle
Analysis.
AB - Genome uncoating is a prerequisite for the successful infection of plant viruses
in host plants. Thus far, little is known about the genome uncoating of the
Carnation mottle virus (CarMV). Here, we obtained two reconstructions of CarMV at
pH7 in the presence (Ca-pH7) and absence (EDTA-pH7) of calcium ions by Cryo-EM
single particle analysis, which achieved 6.4 A and 8 A resolutions respectively.
Our results showed that chelation of the calcium ions under EDTA-pH7 resulted in
reduced interaction between the subunits near the center of the asymmetric unit
but not overall size change of the viral particles, which indicated that the role
of the calcium ions in CarMV was not predominantly for the structural
preservation. Part of the genomic RNA closest to the capsid was found to be
located near the center of the asymmetric unit, which might result from the
interaction between genomic RNA and Lys194 residues. Together with the
electrostatic potential analysis on the inner surface of the asymmetric unit, the
reduced interaction near the center of the asymmetric unit under EDTA-pH7
suggested that the genome release of CarMV might be realized through the center
of the asymmetric unit.
PMID- 26442594
TI - Ruthenium chalcogenonitrosyl and bridged nitrido complexes containing chelating
sulfur and oxygen ligands.
AB - Ruthenium thio- and seleno-nitrosyl complexes containing chelating sulfur and
oxygen ligands have been synthesised and their de-chalcogenation reactions have
been studied. The reaction of mer-[Ru(N)Cl3(AsPh3)2] with elemental sulfur and
selenium in tetrahydrofuran at reflux afforded the chalcogenonitrosyl complexes
mer-[Ru(NX)Cl3(AsPh3)2] [X = S (1), Se (2)]. Treatment of 1 with KN(R2PS)2
afforded trans-[Ru(NS)Cl{N(R2PS)2}2] [R = Ph (3), Pr(i) (4), Bu(t) (5)].
Alternatively, the thionitrosyl complex 5 was obtained from [Bu(n)4N][Ru(N)Cl4]
and KN(Bu(t)2PS)2, presumably via sulfur atom transfer from [N(Bu(t)2PS)2](-) to
the nitride. Reactions of 1 and 2 with NaLOEt (LOEt(-) = [Co(eta(5)
C5H5){P(O)(LOEt)2}3](-)) gave [Ru(NX)LOEtCl2] (X = S (8), Se (9)). Treatment of
[Bu(n)4N][Ru(N)Cl4] with KN(R2PS)2 produced Ru(IV)-Ru(IV)MU-nitrido complexes
[Ru2(MU-N){N(R2PS)2}4Cl] [R = Ph (6), Pr(i) (7)]. Reactions of 3 and 9 with PPh3
afforded 6 and [Ru(NPPh3)LOEtCl2], respectively. The desulfurisation of 5 with
[Ni(cod)2] (cod = 1,5-cyclooctadiene) gave the mixed valance Ru(III)-Ru(IV)MU
nitrido complex [Ru2(MU-N){N(Bu(t)2PS)2}4] (10) that was oxidised by [Cp2Fe](PF6)
to give the Ru(IV)-Ru(IV) complex [Ru2(MU-N){N(Bu(t)2PS)2}4](PF6) ([10]PF6). The
crystal structures of 1, 2, 3, 7, 9 and 10 have been determined.
PMID- 26442595
TI - Diacerein protects against iodoacetate-induced osteoarthritis in the femorotibial
joints of rats.
AB - The present study was undertaken to investigate the effect of diacerein on the
histopathology of articular cartilage and subchondral bone of the femorotibial
joint in rats. Osteoarthritis was induced in rats after single intra-articular
injection of sodium iodoacetate. Rats were sacrificed 1, 2, 4, and 8 weeks post
intra-articular injection to evaluate the progression of histopathogenesis of
osteoarthritis. Diacerein was orally administered (15 mg/kg) once daily post 1
and 2 weeks of iodoacetate injection in two groups, respectively, for up to 12
weeks. Articular cartilage and subchondral bone of the rats of both groups were
examined after 8 and 12 weeks, respectively. Quantitative histological analyses
were performed by scoring these sections as per the OARSI system. Chondroitin
sulfate was also estimated in articular cartilage by decrease in absorbance of
methylene blue on complexation with chondroitin sulfate using a
spectrophotometer. Intra-articular injection of iodoacetate induced loss of
articular cartilage with progressive subchondral bone sclerosis and degeneration.
Based on histopathological and biochemical findings, diacerein treatment showed
chondroprotective effect. Furthermore, the chondroprotective effect of diacerein
was found to be more pronounced after 12 weeks as compared to 8 weeks in both
cases (i.e., post 1 and 2 weeks of iodoacetate injection). Similar results were
observed by investigation of chondroitin sulfate during biochemical study,
showing the chondroprotective effect. In conclusion, diacerein exhibits
chondroprotective effect in rats with late onset of action.
PMID- 26442596
TI - HDAC inhibitor misprocesses bantam oncomiRNA, but stimulates hid induced
apoptotic pathway.
AB - Apoptosis or programmed cell death is critical for embryogenesis and tissue
homeostasis. Uncontrolled apoptosis leads to different human disorders including
immunodeficiency, autoimmune disorder and cancer. Several small molecules that
control apoptosis have been identified. Here, we have shown the functional role
of triazole derivative (DCPTN-PT) that acts as a potent HDAC inhibitor and mis
express proto onco microRNA (miRNA) bantam. To further understanding the
mechanism of action of the molecule in apoptotic pathway, a series of experiments
were also performed in Drosophila, a well known model organism in which the
nature of human apoptosis is very analogous. DCPTN-PT mis processes bantam
microRNA and alters its down regulatory target hid function and cleavage of
Caspase-3 which in turn influence components of the mitochondrial apoptotic
pathway in Drosophila. However regulatory microRNAs in other pro-apoptotic genes
are not altered. Simultaneously, treatment of same molecule also affects the
mitochondrial regulatory pathway in human tumour cell lines suggesting its
conservative nature between fly and human. It is reasonable to propose that
triazole derivative (DCPTN-PT) controls bantam oncomiRNA and increases hid
induced apoptosis and is also able to influence mitochondrial apoptotic pathway.
PMID- 26442597
TI - Expansile crosslinked polymersomes for pH sensitive delivery of doxorubicin.
AB - We report a new crosslinked polymersome with pH-responsive swelling properties
through acidic hydrolysis of hydrophobic contents from the amphiphilic polymer
chains. Its unique stability under physiological conditions and large swelling
capability under low pH conditions give this polymersome promising potential for
anticancer drug delivery.
PMID- 26442598
TI - Direct regulation of the natural competence regulator gene tfoX by cyclic AMP
(cAMP) and cAMP receptor protein (CRP) in Vibrios.
AB - TfoX (Sxy) and CRP are two important competence activators. The link between tfoX
and CRP has been shown in H. influenza but lacking evidence of direct
interaction. Recently a Sxy-dependent CRP (CRP-S) site autoregulating Sxy was
reported in E. coli. Here, we show that the cAMP-CRP complex transcriptionally
regulates tfoX expression through multiple canonical CRP (CRP-N) sites in
Vibrios. This conclusion is supported by an analysis of the tfoX mRNA levels and
tfoX transcriptional reporter fusions. The reduced expression of tfoX(VC) was
restored by trans-complementation of crp in ?crp and by exogenous cAMP in ?cya. A
promoter deletion analysis and the site-directed mutagenesis of the putative CRP
N sites revealed the presence of two functional CRP-N sites. The direct binding
of cAMP-CRP to the tfoX(VC)promoter was demonstrated by EMSA assays.
Additionally, the transcriptional start site (TSS) of tfoX(VF) in V. fluvialis
was determined, and -10/-35 regions were predicted. Further comparison of the
tfoX promoter in Vibrios revealed the existence of similar -10 motifs and
putative CRP-N sites, indicating the conserved mechanism of CRP regulation on
tfoX. Our study demonstrates the direct binding of the cAMP-CRP complex to tfoX
promoter, and broadens the understanding of the molecular mechanism regulating
tfoX in Vibrios.
PMID- 26442599
TI - Lateral Hypothalamus GABAergic Neurons Modulate Consummatory Behaviors Regardless
of the Caloric Content or Biological Relevance of the Consumed Stimuli.
AB - It was recently reported that activation of a subset of lateral hypothalamus (LH)
GABAergic neurons induced both appetitive (food-seeking) and consummatory
(eating) behaviors in vGat-ires-cre mice, while inhibition or deletion of
GABAergic neurons blunted these behaviors. As food and caloric-dense liquid
solutions were used, the data reported suggest that these LH GABAergic neurons
may modulate behaviors that function to maintain homeostatic caloric balance.
Here we report that chemogenetic activation of this GABAergic population in vGat
ires-cre mice increased consummatory behavior directed at any available stimulus,
including those entailing calories (food, sucrose, and ethanol), those that do
not (saccharin and water), and those lacking biological relevance (wood).
Chemogenetic inhibition of these neurons attenuated consummatory behaviors. These
data indicate that LH GABAergic neurons modulate consummatory behaviors
regardless of the caloric content or biological relevance of the consumed
stimuli.
PMID- 26442600
TI - Varenicline-Induced Elevation of Dopamine in Smokers: A Preliminary [(11)C]-(+)
PHNO PET Study.
AB - Varenicline, a nicotinic partial agonist, is the most effective treatment for
tobacco use disorder. However, its mechanism of action is still unclear and may
involve stimulating dopaminergic transmission. Here we used PET imaging with
[(11)C]-(+)-PHNO to explore for the first time the impact of varenicline on
dopamine transmission in the D2-rich striatum and D3-rich extra-striatal regions
and its relationship with craving, withdrawal and smoking. Eleven treatment
seeking smokers underwent two PET scans with [(11)C]-(+)-PHNO, each following 12
h overnight smoking abstinence both prior to receiving varenicline and following
10-11 days of varenicline treatment (ie, at steady-state drug levels). Subjective
measures of craving and urges to smoke were also assessed on the days of the PET
scans. Varenicline treatment significantly reduced [(11)C]-(+)-PHNO binding in
the dorsal caudate (p=0.008) and reduced some craving measures. These findings
provide the first evidence that varenicline is able to increase DA levels in the
human brain, a factor that may contribute to its therapeutic efficacy.
PMID- 26442601
TI - GABAergic Signaling within a Limbic-Hypothalamic Circuit Integrates Social and
Anxiety-Like Behavior with Stress Reactivity.
AB - The posterior hypothalamic nucleus (PH) stimulates autonomic stress responses.
However, the role of the PH in behavioral correlates of psychiatric illness, such
as social and anxiety-like behavior, is largely unexplored, as is the
neurochemistry of PH connectivity with limbic and neuroendocrine systems. Thus,
the current study tested the hypothesis that GABAergic signaling within the PH is
a critical link between forebrain behavior-regulatory nuclei and the
neuroendocrine hypothalamus, integrating social and anxiety-related behaviors
with physiological stress reactivity. To address this hypothesis, GABAA receptor
pharmacology was used to locally inhibit or disinhibit the PH immediately before
behavioral measures of social and anxiety-like behavior in rats. Limbic
connectivity of the PH was then established by simultaneous co-injection of
anterograde and retrograde tracers. Further, the role of PH GABAergic signaling
in neuroendocrine stress responses was tested via inhibition/disinhibition of the
PH. These studies determined a prominent role for the PH in the expression of
anxiety-related behaviors and social withdrawal. Histological analyses revealed
divergent stress-activated limbic input to the PH, emanating predominantly from
the prefrontal cortex, lateral septum, and amygdala. PH projections also targeted
both parvicellular and magnocellular peptidergic neurons in the paraventricular
and supraoptic hypothalamus. Further, GABAA receptor pharmacology determined an
excitatory effect of the PH on neuroendocrine responses to stress. These data
indicate that the PH represents an important stress-integrative center,
regulating behavioral processes and connecting the limbic forebrain with
neuroendocrine systems. Moreover, the PH appears to be uniquely situated to have
a role in stress-related pathologies associated with limbic-hypothalamic
dysfunction.
PMID- 26442603
TI - Raising the barrier for photoinduced DNA charge injection with a cyclohexyl
artificial base pair.
AB - The effects of an artificial cyclohexyl base pair on the quantum yields of
fluorescence and dynamics of charge separation and charge recombination have been
investigated for several synthetic DNA hairpins. The hairpins possess
stilbenedicarboxamide, perylenediimide, or naphthalenediimide linkers and base
paired stems. In the absence of the artificial base pair hole injection into both
adenine and guanine purine bases is exergonic and irreversible, except in the
case of stilbene with adenine for which it is slightly endergonic and reversible.
Insertion of the artificial base pair renders hole injection endergonic or
isoergonic except in the case of the powerful naphthalene acceptor for which it
remains exergonic. Both hole injection and charge recombination are slower for
the naphthalene acceptor in the presence of the artificial base pair than in its
absence. The effect of an artificial base pair on charge separation and charge
recombination in hairpins possessing stilbene and naphthalene acceptor linkers
and a stilbenediether donor capping group has also been investigated. In the case
of the stilbene acceptor-stilbene donor capped hairpins photoinduced charge
separation across six base pairs is efficient in the absence of the artificial
base pair but does not occur in its presence. In the case of the naphthalene
acceptor-stilbene donor capped hairpins the artificial base pair slows but does
not stop charge separation and charge recombination, leading to the formation of
long-lived charge separated states.
PMID- 26442602
TI - State-Dependent Partial Occlusion of Cortical LTP-Like Plasticity in Major
Depression.
AB - The synaptic plasticity hypothesis of major depressive disorder (MDD) posits that
alterations in synaptic plasticity represent a final common pathway underlying
the clinical symptoms of the disorder. This study tested the hypotheses that
patients with MDD show an attenuation of cortical synaptic long-term potentiation
(LTP)-like plasticity in comparison with healthy controls, and that this
attenuation recovers after remission. Cortical synaptic LTP-like plasticity was
measured using a transcranial magnetic stimulation protocol, ie, paired
associative stimulation (PAS), in 27 in-patients with MDD according to ICD-10
criteria and 27 sex- and age-matched healthy controls. The amplitude of motor
evoked potentials was measured before and after PAS. Patients were assessed
during the acute episode and at follow-up to determine the state- or trait
character of LTP-like changes. LTP-like plasticity, the PAS-induced increase in
motor-evoked potential amplitudes, was significantly attenuated in patients with
an acute episode of MDD compared with healthy controls. Patients with remission
showed a restoration of synaptic plasticity, whereas the deficits persisted in
patients without remission, indicative for a state-character of impaired LTP-like
plasticity. The results provide first evidence for a state-dependent partial
occlusion of cortical LTP-like plasticity in MDD. This further identifies
impaired LTP-like plasticity as a potential pathomechanism and treatment target
of the disorder.
PMID- 26442604
TI - Differential activation of renal sympathetic burst amplitude and frequency during
hypoxia, stress and baroreflexes with chronic angiotensin treatment.
AB - NEW FINDINGS: What is the central question of this study? Is the elevated tonic
renal nerve activity induced by chronic angiotensin administration mediated by
recruitment or increased firing frequency and does this occur via stress,
chemoreflex or baroreflex pathways? What is the main finding and its importance?
Long-term angiotensin treatment in rabbits elevates renal sympathetic nerve
activity by recruitment of previously silent fibres. This was similar to the
effect of chemoreflex stimulation, but not to stress or baroreceptor activation,
suggesting that presympathetic pathways activated by angiotensin may be common to
those activated by chemoreceptors. Modulation of sympathetic nerve activity
involves control by the CNS of the amplitude of neural discharges, reflecting
recruitment of neurons and their firing frequency. We tested whether elevated
tonic renal sympathetic nerve activity (RSNA) induced by chronic angiotensin
administration is mediated by recruitment or increased firing frequency and
whether this is characteristic of the pattern observed with activation of stress,
chemoreflex or baroreflex pathways. Conscious rabbits treated with angiotensin II
for 12 weeks to increase blood pressure by 10-30% were subjected to stress (air
jet), hypoxia (10% O2 + 3% CO2) and drug-induced changes in blood pressure to
produce baroreflexes. Total RSNA and RSNA burst amplitude were scaled to 100
normalized units (n.u.) by the maximal response to smoke. After 12 weeks of
treatment, blood pressure was 17% higher than baseline 68 +/- 1 mmHg (P = 0.02).
Compared with sham treatment, total RSNA and burst amplitude were +82% (P <
0.001) and 39% (P = 0.04) greater, but burst frequency was similar. Total RSNA
increased during hypoxia (+38% from 4.9 +/- 0.7 n.u.), owing to greater
amplitude, but not frequency. Air-jet stress increased total RSNA (+44% from 4.3
+/- 0.5 n.u.) and burst frequency (+21% from 5.4 +/- 0.7 bursts s(-1) ), but not
amplitude. Angiotensin enhanced total RSNA responses to both air jet (+33%) and
hypoxia (+58%), but only increased the amplitude response to air jet. The RSNA
baroreflexes reset to the higher blood pressure, but amplitude or frequency was
not differentially altered. Chronic angiotensin treatment elevated RSNA by
recruitment of neurons, which is similar to chemoreflex stimulation, but not to
stress or baroreceptor activation, suggesting that presympathetic pathways
activated by angiotensin may be common to those activated by chemoreceptors.
PMID- 26442606
TI - Chemiluminometric Immunosensor for High-Sensitivity Cardiac Troponin I Employing
a Polymerized Enzyme Conjugate as a Tracer.
AB - To detect high-sensitivity cardiac troponin I (hs-cTnI; <0.01 ng/mL) at points of
care, we developed a rapid immunosensor by using horseradish peroxidase
polymerized in 20 molecules on average (Poly-HRP) as a tracer conjugated with
streptavidin (SA-Poly-HRP). As shown in the conventional system, enhanced
sensitivity could be achieved by using a sequential binding scheme for the
complex formation to contain the huge molecular tracer. We used a 2-dimensional
chromatographic technology to carry out the sequential bindings in cross-flow
directions. After the complex formation of antigen-antibody with analyte in a
vertical direction, SA-Poly-HRP was horizontally supplied across the membrane
strip for additional binding via a biotin-SA linkage. The HRP substrate was
subsequently supplied along the same direction to produce a chemiluminometric
signal, which was measured by a cooled charge-coupled device. Hs-cTnI analysis
was completed in this format within 25 min, and the results showed a high
correlation with those of the CentaurXP(r) reference system (R(2) > 0.99). The
detection limit of the rapid immunosensor was 0.003 +/- 0.001 ng/mL cTnI,
corresponding to a 10-fold improvement compared to results using the plain enzyme
tracer. This demonstrated the measurement of hs-cTnI in a much more cost
effective manner compared to the automated versions currently available.
PMID- 26442607
TI - Onset and progression of de novo donor-specific anti-human leukocyte antigen
antibodies after BK polyomavirus and preemptive immunosuppression reduction.
AB - BACKGROUND: BK polyomavirus (BKPyV) viremia/nephropathy and reduction in
immunosuppression following viremia may increase the risk of alloimmune
activation and allograft rejection. This study investigates the impact of BKPyV
viremia on de novo donor anti-human leukocyte antigen (HLA)-specific antibodies
(dnDSA). PATIENTS AND METHODS: All primary renal transplants at East Carolina
University from March 1999 to December 2010, with at least 1 post-transplant
BKPyV viral load testing, were analyzed. Patients were negative for anti-HLA
antibodies to donor antigens (tested via single antigen beads) at transplantation
and at first BKPyV testing. RESULTS: Nineteen of 174 patients (11%) tested
positive for BKPyV viremia. Within 24 months of BKPyV viremia detection, 79% of
BKPyV-viremic patients developed dnDSA. Only 20% of BKPyV viremia-persistent
cases, compared to 86% of BKPyV viremia-resolved cases, developed dnDSA (P =
0.03). Poor allograft survival was evident in BKPyV viremia-persistent patients
(60% failure by 2 years post BKPyV diagnosis) and in BKPyV viremia-resolved
patients with dnDSA (5-year post BKPyV diagnosis allograft survival of 48%).
CONCLUSIONS: Post-transplant BKPyV viremia and preemptive immunosuppression
reduction is associated with high rates of dnDSA. When preemptively treating
BKPyV viremia, dnDSA should be monitored to prevent allograft consequences.
PMID- 26442608
TI - Rational Design of a Lanthanide-Based Complex Featuring Different Single-Molecule
Magnets.
AB - The rational synthesis of the 2-{1-methylpyridine-N-oxide-4,5-[4,5
bis(propylthio)tetrathiafulvalenyl]-1H-benzimidazol-2-yl}pyridine ligand (L) is
described. It led to the tetranuclear complex [Dy4(tta)12(L)2] (Dy-Dy2-Dy) after
coordination reaction with the precursor Dy(tta)3?2 H2O (tta(-) = 2
thenoyltrifluoroacetonate). The X-ray structure of Dy-Dy2-Dy can be described as
two terminal mononuclear units bridged by a central antiferromagnetically coupled
dinuclear complex. The terminal N2O6 and central O8 environments are described as
distorted square antiprisms. The ac magnetism measurements revealed a strong out
of-phase signal of the magnetic susceptibility with two distinct sets of data.
The high- and low-frequency components were attributed to the two terminal
mononuclear single-molecule magnets (SMMs) and the central dinuclear SMM,
respectively. A magnetic hysteresis loop was detected at very low temperature.
From both structural and magnetic points of view, the tetranuclear SMM Dy-Dy2-Dy
is a self-assembly of two known mononuclear SMMs bridged by a known dinuclear
SMM.
PMID- 26442609
TI - Metal-to-insulator switching in quantum anomalous Hall states.
AB - After decades of searching for the dissipationless transport in the absence of
any external magnetic field, quantum anomalous Hall effect (QAHE) was recently
achieved in magnetic topological insulator films. However, the universal phase
diagram of QAHE and its relation with quantum Hall effect (QHE) remain to be
investigated. Here, we report the experimental observation of the giant
longitudinal resistance peak and zero Hall conductance plateau at the coercive
field in the six quintuple-layer (Cr(0.12)Bi(0.26)Sb(0.62))2Te3 film, and
demonstrate the metal-to-insulator switching between two opposite QAHE plateau
states up to 0.3 K. Moreover, the universal QAHE phase diagram is confirmed
through the angle-dependent measurements. Our results address that the quantum
phase transitions in both QAHE and QHE regimes are in the same universality
class, yet the microscopic details are different. In addition, the realization of
the QAHE insulating state unveils new ways to explore quantum phase-related
physics and applications.
PMID- 26442610
TI - Bortezomib-thalidomide-dexamethasone (VTD) is superior to bortezomib
cyclophosphamide-dexamethasone (VCD) as induction therapy prior to autologous
stem cell transplantation in multiple myeloma.
PMID- 26442611
TI - Incidence and description of autoimmune cytopenias during treatment with
ibrutinib for chronic lymphocytic leukemia.
AB - Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary
autoimmune cytopenias (AICs). Ibrutinib is an irreversible inhibitor of Bruton's
tyrosine kinase approved for the treatment of relapsed CLL and CLL with del(17p).
The effect of ibrutinib treatment on the incidence of AIC is currently unknown.
We reviewed medical records of 301 patients treated with ibrutinib, as
participants in therapeutic clinical trials at The Ohio State University
Comprehensive Cancer Center between July 2010 and July 2014. Subjects were
reviewed with respect to past history of AIC, and treatment-emergent AIC cases
were identified. Before starting ibrutinib treatment, 26% of patients had
experienced AIC. Information was available for a total of 468 patient-years of
ibrutinib exposure, during which there were six cases of treatment-emergent AIC.
This corresponds to an estimated incidence rate of 13 episodes for every 1000
patient-years of ibrutinib treatment. We further identified 22 patients receiving
therapy for AIC at the time ibrutinib was started. Of these 22 patients, 19 were
able to discontinue AIC therapy. We found that ibrutinib treatment is associated
with a low rate of treatment-emergent AIC. Patients with an existing AIC have
been successfully treated with ibrutinib and subsequently discontinued AIC
therapy.
PMID- 26442613
TI - Familial risk of non-Hodgkin lymphoma by sex, relationship, age at diagnosis and
histology: a joint study from five Nordic countries.
AB - We aimed to estimate stratified absolute (cumulative) and relative (standardized
incidence ratios; SIRs) risks of non-Hodgkin lymphoma (NHL) in relatives of NHL
patients. A cohort of 169 830 first-degree relatives of 45 406 NHL patients who
were diagnosed between 1955 and 2010 in five European countries was followed for
cancer incidence. The lifetime (0-79 year) cumulative risk of NHL in siblings of
a patient with NHL was 1.6%, which represents a 1.6-fold increased risk (SIR=1.6,
95% confidence interval (CI)=1.2-1.9) over the general population risk. NHL risk
among parent-offspring pairs was increased up to 1.4-fold (95% CI=1.3-1.5;
lifetime risk 1.4%). The lifetime risk was higher when NHL was diagnosed in a
sister (2.5% in her brothers and 1.9% in her sisters) or a father (1.7% in his
son). When there were ?2 NHL patients diagnosed in a family, the lifetime NHL
risk for relatives was 2.1%. Depending on sex and age at diagnosis, twins had a
3.1-12.9% lifetime risk of NHL. Family history of most of the histological
subtypes of NHL increased the risk of concordant and some discordant subtypes.
Familial risk did not significantly change by age at diagnosis of NHL in
relatives. Familial risk of NHL was not limited to early onset cases.
PMID- 26442612
TI - Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in
patients with lower-risk myelodysplastic syndromes.
AB - CC-486, the oral formulation of azacitidine (AZA), is an epigenetic modifier and
DNA methyltransferase inhibitor in clinical development for treatment of
hematologic malignancies. CC-486 administered for 7 days per 28-day treatment
cycle was evaluated in a phase 1 dose-finding study. AZA has a short plasma half
life and DNA incorporation is S-phase-restricted; extending CC-486 exposure may
increase the number of AZA-affected diseased target cells and maximize
therapeutic effects. Patients with lower-risk myelodysplastic syndromes (MDS)
received 300 mg CC-486 once daily for 14 days (n=28) or 21 days (n=27) of
repeated 28-day cycles. Median patient age was 72 years (range 31-87) and 75% of
patients had International Prognostic Scoring System Intermediate-1 risk MDS.
Median number of CC-486 treatment cycles was 7 (range 2-24) for the 14-day dosing
schedule and 6 (1-24) for the 21-day schedule. Overall response (complete or
partial remission, red blood cell (RBC) or platelet transfusion independence
(TI), or hematologic improvement) (International Working Group 2006) was attained
by 36% of patients receiving 14-day dosing and 41% receiving 21-day dosing. RBC
TI rates were similar with both dosing schedules (31% and 38%, respectively). CC
486 was generally well-tolerated. Extended dosing schedules of oral CC-486 may
provide effective long-term treatment for patients with lower-risk MDS.
PMID- 26442614
TI - Switchable Ultrathin Quarter-wave Plate in Terahertz Using Active Phase-change
Metasurface.
AB - Metamaterials open up various exotic means to control electromagnetic waves and
among them polarization manipulations with metamaterials have attracted intense
attention. As of today, static responses of resonators in metamaterials lead to a
narrow-band and single-function operation. Extension of the working frequency
relies on multilayer metamaterials or different unit cells, which hinder the
development of ultra-compact optical systems. In this work, we demonstrate a
switchable ultrathin terahertz quarter-wave plate by hybridizing a phase change
material, vanadium dioxide (VO2), with a metasurface. Before the phase
transition, VO2 behaves as a semiconductor and the metasurface operates as a
quarter-wave plate at 0.468 THz. After the transition to metal phase, the quarter
wave plate operates at 0.502 THz. At the corresponding operating frequencies, the
metasurface converts a linearly polarized light into a circularly polarized
light. This work reveals the feasibility to realize tunable/active and extremely
low-profile polarization manipulation devices in the terahertz regime through the
incorporation of such phase-change metasurfaces, enabling novel applications of
ultrathin terahertz meta-devices.
PMID- 26442615
TI - Protective Role of Crocin Against Nicotine-induced Damages on Male Mice Liver.
AB - BACKGROUND: Nicotine is a major pharmacologically active substance in cigarette
smoke. It is mainly metabolized in liver and causes devastating effects. Crocin
is the chemical ingredient primarily responsible for the color of saffron. It has
different pharmacological effects such as antioxidant and anticancer. This study
was designed to evaluate the protective role of crocin against nicotine on the
liver of mice. METHODS: Forty-eight mice were equally divided into 8 groups;
control (normal saline), nicotine (2.5 mg/kg), crocin (12.5, 25 and 50 mg/kg) and
crocin plus nicotine treated groups. Saline, crocin, nicotine and crocin/nicotine
(once a day) were intraperitoneally injected for 4 weeks. The liver weight and
histology, aspartate aminotransferase (AST), alanine aminotransferase (ALT),
alkaline phosphatase (ALP), and serum nitric oxide levels have been studied.
RESULTS: The results indicated that nicotine administration significantly
decreased liver weight (48.37%) and increased the mean diameter of hepatocyte
(239%), central hepatic vein (28.45%), liver enzymes level (ALP 29.43%, AST
21.81%, ALT 21.55%), and blood serum nitric oxide level (57.18%) compared to
saline group (P < 0.05). However, crocin and crocin plus nicotine administration
significantly boosted liver weight (49.54%) and decreased the mean diameter of
hepatocyte (40.48%), central hepatic vein (15.44%), liver enzymes (ALP 22.02%,
AST 19.05%, ALT 23.11%), and nitric oxide levels (35.80%) in all groups compared
to nicotine group (percentages represent the maximum dose) (P < 0.05).
CONCLUSIONS: Crocin showed its partly protective effect against nicotine-induced
liver toxicity.
PMID- 26442616
TI - Neonatal brain abnormalities associated with autism spectrum disorder in children
born very preterm.
AB - Very preterm (VP) survivors are at increased risk of autism spectrum disorder
(ASD) compared with term-born children. This study explored whether neonatal
magnetic resonance (MR) brain features differed in VP children with and without
ASD at 7 years. One hundred and seventy-two VP children (<30 weeks' gestation or
<1250 g birth weight) underwent structural brain MR scans at term equivalent age
(TEA; 40 weeks' gestation +/-2 weeks) and were assessed for ASD at 7 years of
age. The presence and severity of white matter, cortical gray matter, deep
nuclear gray matter, and cerebellar abnormalities were assessed, and total and
regional brain volumes were measured. ASD was diagnosed using a standardized
parent report diagnostic interview and confirmed via an independent assessment.
Eight VP children (4.7%) were diagnosed with ASD. Children with ASD had more
cystic lesions in the cortical white matter at TEA compared with those without
ASD (odds ratio [OR] 8.7, 95% confidence interval [CI] 1.5, 51.3, P = 0.02).
There was also some evidence for smaller cerebellar volumes in children with ASD
compared with those without ASD (OR = 0.82, CI = 0.66, 1.00, P = 0.06). Overall,
the results suggest that VP children with ASD have different brain structure in
the neonatal period compared with those who do not have ASD. Autism Res 2016, 9:
543-552. (c) 2015 International Society for Autism Research, Wiley Periodicals,
Inc.
PMID- 26442617
TI - Effects of landscape matrix on population connectivity of an arboreal mammal,
Petaurus breviceps.
AB - Ongoing habitat loss and fragmentation is considered a threat to biodiversity as
it can create small, isolated populations that are at increased risk of
extinction. Tree-dependent species are predicted to be highly sensitive to forest
and woodland loss and fragmentation, but few studies have tested the influence of
different types of landscape matrix on gene flow and population structure of
arboreal species. Here, we examine the effects of landscape matrix on population
structure of the sugar glider (Petaurus breviceps) in a fragmented landscape in
southeastern South Australia. We collected 250 individuals across 12 native
Eucalyptus forest remnants surrounded by cleared agricultural land or exotic
Pinus radiata plantations and a large continuous eucalypt forest. Fifteen
microsatellite loci were genotyped and analyzed to infer levels of population
differentiation and dispersal. Genetic differentiation among most forest patches
was evident. We found evidence for female philopatry and restricted dispersal
distances for females relative to males, suggesting there is male-biased
dispersal. Among the environmental variables, spatial variables including
geographic location, minimum distance to neighboring patch, and degree of
isolation were the most important in explaining genetic variation. The
permeability of a cleared agricultural matrix to dispersing gliders was
significantly higher than that of a pine matrix, with the gliders dispersing
shorter distances across the latter. Our results added to previous findings for
other species of restricted dispersal and connectivity due to habitat
fragmentation in the same region, providing valuable information for the
development of strategies to improve the connectivity of populations in the
future.
PMID- 26442618
TI - Assessment of phytochemicals and antioxidant activities of raw and germinating
Ceiba pentandra (kapok) seeds.
AB - To determine the significance of germination on phytochemical constituents and
non-enzymatic antioxidant activities of Ceiba pentandra seed extracts.
Phytochemicals and antioxidant activities of raw and germinating seeds of Ceiba
pentandra were estimated by different methods. The levels of phytochemical
constituents were influenced by germination and increased except alkaloids and
tannins, which were decreased significantly during germination. Among non
enzymatic antioxidants like DPPH, FRAP, reducing assay and hydroxyl radical
scavenging activity all showed improved activity compared with non-germinating
seeds. This may be due to various reactive oxygen species (ROS) that were
generated as by-products of metabolism during germination. This group of ROS
included superoxide radicals (O2), hydrogen peroxide radicals (H2O2) and hydroxyl
radicals (OH). The formation of these oxygen radicals resulted in the
accumulation of lipid hydroperoxides by radical chain oxidation via phospholipids
peroxy radicals within membranes. Therefore, it was hypothesized that this could
be related to the increase of antioxidant activity in large unilamellar vesicles
observed in germinated seeds. The implication of this study is that the Ceiba
pentandra seeds as natural antioxidant agents and put forward the possibility of
employing for therapeutic potential.
PMID- 26442619
TI - Differential Rates of Inadvertent Intravascular Injection during Lumbar
Transforaminal Epidural Injections Using Blunt-Tip, Pencil-Point, and Catheter
Extension Needles.
AB - OBJECTIVE: To quantify the incidence of inadvertent vascular penetration during
lumbosacral transforaminal epidural injections using blunt-tip, pencil-point, and
catheter-extension needles. STUDY DESIGN/SETTING: This is a prospective,
observational, consecutive cohort study. SUBJECTS: Two hundred consecutive
patients undergoing lumbosacral transforaminal epidural injections at an academic
outpatient spine center. METHODS: Four hundred seventy-five fluoroscopically
guided lumbosacral transforaminal epidural injections were performed on
consecutively consenting patients by one interventional spine physician, using
three different needle types. The presence or absence of vascular uptake was
determined during contrast injection under live fluoroscopy. RESULTS: Vascular
uptake of contrast was observed in 58 of the total 475 injections, for an overall
incidence of 12.2%. By needle type, the incidence of inadvertent vascular uptake
was 16.6% (26/157) in the pencil-point group, 15.6% (24/154) in the blunt-tip
group, and 4.9% (8/164) in the catheter-extension group. The difference in rates
is statistically significant between the catheter-extension needle group and both
the pencil-point group (P = 0.0009) and blunt-tip group (P = 0.0024). A secondary
analysis was performed to quantify the incidence of functional pitfalls between
needle groups, with a significantly lower incidence in the pencil-point group
compared to both the catheter-extension (P = 0.0148) and blunt-tip needle (P =
0.0288) groups. CONCLUSIONS: Blunt-tip and pencil-point needles have comparable
risk of inadvertent vascular injection during lumbosacral transforaminal
injections. Catheter-extension needles demonstrated a reduce incidence of
vascular uptake, but also result in a significantly higher rate of functional
pitfalls that limits their usefulness in routine practice.
PMID- 26442620
TI - Management of Rapidly Ascending Driveline Tunnel Infection.
AB - We present a case of rapidly ascending left ventricular assist device driveline
and tunnel infection in a patient with a long length of driveline buried beyond
the distal velour coating. Device salvage with radical debridement, exit site
relocation, and local tissue advancement is described. The findings in this case
suggest that the interface between nonvelour covered driveline and subcutaneous
tissue can become the nidus of a virulent ascending infection because of poor
tissue ingrowth.
PMID- 26442621
TI - Effect of High-Dose Statin Pretreatment on the Incidence of Periprocedural
Myocardial Infarction in Patients Undergoing Percutaneous Coronary Intervention:
Grading the Evidence Through a Cumulative Meta-analysis.
AB - BACKGROUND: Previous studies have showed that high-dose statin pretreatment could
reduce the incidence of periprocedural myocardial infarction (PMI) in patients
undergoing percutaneous coronary intervention (PCI). However, previous analyses
have not performed reliable grading of evidence. HYPOTHESIS: In previous
analyses, it supposed that the high-dose statin pretreatment was effective in
reduction of the rate of PMI. In this analysis, we evaluated the effect of high
dose statin pretreatment on the reduction of rate of PMI based on a cumulative
meta-analysis and grading of evidence. METHODS: We assembled the relevant
published randomized controlled trials that compared the efficacy of high-dose
statin pretreatment prior to PCI. We evaluated the risk of PMI by a cumulative
meta-analysis, with subgroups stratified by clinical classifications and
different statin histories, and we conducted explicit grading of evidence.
RESULTS: High-dose statin pretreatment caused a 55% reduction in PMI through this
cumulative meta-analysis of 23 RCTs (odds ratio [OR]: 0.45, 95% confidence
interval [CI]: 0.37-0.54). The effect of high-dose statin pretreatment was
significant for the stable angina subgroup (OR: 0.42, 95% CI: 0.32-0.56), ACS
subgroup (OR: 0.43, 95% CI: 0.29-0.64), and the mixed presentation subgroup (OR:
0.50, 95% CI: 0.36-0.70). In different statin therapy histories, high-dose statin
pretreatment reduced incidence of PMI 55% in the statin-naive subgroup (OR: 0.45,
95% CI: 0.36-0.56) and 54% in the low-dose statin subgroup (OR: 0.46, 95% CI:
0.32-0.66). The GRADE system indicated that the overall evidence quality was
moderate. This finding may strengthen the confidence in any recommendations.
CONCLUSIONS: High-dose statin pretreatment can reduce the rate of PMI,
irrespective of either the clinical presentation or previous statin-treatment
history. Importantly, the overall GRADE evidence quality was moderate.
PMID- 26442622
TI - Evolutionary conservation of molecular structure and antiviral function of a
viral receptor, LGP2, in amphioxus Branchiostoma japonicum.
AB - RIG-I-like (where RIG-I is retinoic acid inducible gene I) receptor LGP2 (where
LGP2 is laboratory of genetics and physiology) is an important intracellular
receptor that recognizes viral RNAs in innate immunity, but its origin and
evolution remains unknown. Here we clearly demonstrate the presence of a RIG-I
like receptor, BjLGP2, in the basal chordate amphioxus. It is predominantly
expressed in the hepatic caecum and hindgut, and is upregulated following
challenge with poly(I:C). BjLGP2 is distributed in the cytoplasm of both grouper
spleen and flounder gill (FG) cells, and the recombinant BjLGP2 interacts with
poly(I:C). BjLGP2 can enhance the expression of IFN and IFN-inducible genes in FG
cells upon poly(I:C) challenge. It also significantly induces the expression of
the antiviral genes ifn-i and Mx as well as the signal transduction relevant
genes MAVS, NF-kappaB, and IRF-3 in FG cells upon lymphocystis disease virus
challenge. Moreover, BjLGP2 inhibits the replication of lymphocystis disease
virus in FG cells and the gene transcription of Singapore grouper iridovirus in
grouper spleen cells. This is the first report showing that a LGP2 protein in
invertebrate species (amphioxus) is structurally conserved and plays an antiviral
role similar to that of vertebrate LGP2 proteins.
PMID- 26442623
TI - The ACGME Self-Study-An Opportunity, Not a Burden.
PMID- 26442624
TI - Hydration and ion pair formation in aqueous Y(3+)-salt solutions.
AB - Raman spectra of aqueous yttrium perchlorate, triflate
(trifluoromethanesulfonate), chloride and nitrate solutions were measured over a
broad concentration range (0.198-3.252 mol L(-1)). The spectra range from low
wavenumbers to 4200 cm(-1). A very weak mode at 384 cm(-1) with a full width at
half height at 50 cm(-1) in the isotropic spectrum suggests that the Y(3+)- octa
aqua ion is thermodynamically stable in dilute perchlorate solutions (~0.5 mol L(
1)) while in concentrated perchlorate solutions outer-sphere ion pairs and
contact ion pairs are formed. The octa-hydrate, [Y(OH2)8](3+) was also detected
in a 1.10 mol L(-1) aqueous Y(CF3SO3)3 solution. Furthermore, very weak and broad
depolarized modes could be detected which are assigned to [Y(OH2)8](3+)(aq) at
100, 166, 234 and 320 cm(-1) confirming that a hexa-hydrate is not compatible
with the hydrated species in solution. In yttrium chloride solutions contact ion
pair formation was detected over the measured concentration range from 0.479
3.212 mol L(-1). The contact ion pairs in YCl3(aq) are fairly weak and disappear
with dilution. At a concentration <0.2 mol L(-1) almost all complexes have
disappeared. In YCl3 solutions, with additional HCl, chloro-complexes of the type
[Y(OH2)8-nCln](+3-n) (n = 1,2) are formed. The Y(NO3)3(aq) spectra were compared
with a spectrum of a dilute NaNO3 solution and it was concluded that in
Y(NO3)3(aq) over the concentration range from 2.035-0.198 mol L(-1) nitrato
complexes [Y(OH2)8-n(NO3)ln](+3-n) (n = 1,2) are formed. The nitrato-complexes
are weak and disappear with dilution <0.1 mol L(-1). DFT geometry optimizations
and frequency calculations are reported for both the yttrium-water cluster in the
gas phase and the cluster within a polarizable continuum model in order to
implicitly describe the presence of the bulk solvent. The bond distance and angle
for the square antiprismatic cluster geometry of [Y(OH2)8](3+) with the
polarizable dielectric continuum is in good agreement with data from recent
structural experimental measurements. The DFT frequency of the Y-O stretching
mode of the [Y(OH2)8](3+) cluster, in a polarizable continuum, is at 372 cm(-1)
in satisfactory agreement with the experimental value.
PMID- 26442625
TI - Drosophila chitinous aECM and its cellular interactions during tracheal
development.
AB - The morphology of organs, and hence their proper physiology, relies to a
considerable extent on the extracellular matrix (ECM) secreted by their cells.
The ECM is a structure contributed to and commonly shared by many cells in an
organism that plays an active role in morphogenesis. Increasing evidence
indicates that the ECM not only provides a passive contribution to organ shape
but also impinges on cell behaviour and genetic programmes. The ECM is emerging
as a direct modulator of many aspects of cell biology, rather than as a mere
physical network that supports cells. Here, we review how the apical chitinous
ECM is generated in Drosophila trachea and how cells participate in the formation
of this supracellular structure. We discuss recent findings on the molecular and
cellular events that lead to the formation of this apical ECM (aECM) and how it
is influenced and affects tracheal cell biology.
PMID- 26442627
TI - Circularly polarised luminescence and circular dichroism of l- and d
oligopeptides with multiple pyrenes.
AB - Among l- and d-oligopeptides with multiple pyrenes as pendants, the dipeptides
with two and three pyrenes showed blue-coloured circularly polarised luminescence
as high as |gem|~ (0.86-1.1) * 10(-2) at around 450 nm, reflecting from exciton
couplets of twisted pyrenes.
PMID- 26442628
TI - Ouabain rescues rat nephrogenesis during intrauterine growth restriction by
regulating the complement and coagulation cascades and calcium signaling pathway.
AB - Intrauterine growth restriction (IUGR) is associated with a reduction in the
numbers of nephrons in neonates, which increases the risk of hypertension. Our
previous study showed that ouabain protects the development of the embryonic
kidney during IUGR. To explore this molecular mechanism, IUGR rats were induced
by protein and calorie restriction throughout pregnancy, and ouabain was
delivered using a mini osmotic pump. RNA sequencing technology was used to
identify the differentially expressed genes (DEGs) of the embryonic kidneys. DEGs
were submitted to the Database for Annotation and Visualization and Integrated
Discovery, and gene ontology enrichment analysis and Kyoto Encyclopedia of Genes
and Genomes (KEGG) pathway analysis were conducted. Maternal malnutrition
significantly reduced fetal weight, but ouabain treatment had no significant
effect on body weight. A total of 322 (177 upregulated and 145 downregulated)
DEGs were detected between control and the IUGR group. Meanwhile, 318 DEGs were
found to be differentially expressed (180 increased and 138 decreased) between
the IUGR group and the ouabain-treated group. KEGG pathway analysis indicated
that maternal undernutrition mainly disrupts the complement and coagulation
cascades and the calcium signaling pathway, which could be protected by ouabain
treatment. Taken together, these two biological pathways may play an important
role in nephrogenesis, indicating potential novel therapeutic targets against the
unfavorable effects of IUGR.
PMID- 26442629
TI - In-situ epitaxial growth of graphene/h-BN van der Waals heterostructures by
molecular beam epitaxy.
AB - Van der Waals materials have received a great deal of attention for their
exceptional layered structures and exotic properties, which can open up various
device applications in nanoelectronics. However, in situ epitaxial growth of
dissimilar van der Waals materials remains challenging. Here we demonstrate a
solution for fabricating van der Waals heterostructures. Graphene/hexagonal boron
nitride (h-BN) heterostructures were synthesized on cobalt substrates by using
molecular beam epitaxy. Various characterizations were carried out to evaluate
the heterostructures. Wafer-scale heterostructures consisting of single
layer/bilayer graphene and multilayer h-BN were achieved. The mismatch angle
between graphene and h-BN is below 1 degrees .
PMID- 26442630
TI - Induction of ROS-independent DNA damage by curcumin leads to G2/M cell cycle
arrest and apoptosis in human papillary thyroid carcinoma BCPAP cells.
AB - Previously we found that curcumin, the active constituent of dietary spice
turmeric, showed potent inhibitory effects on the cell growth of thyroid cancer
cells. However, the detailed anti-cancer mechanism of curcumin is still unknown.
In this study, we have reported that curcumin induces significant DNA damage in
human papillary thyroid carcinoma BCPAP cells in a dose-dependent manner as
evidenced by the upregulated phosphorylation of H2A.X at Ser139, which was
further confirmed by the long tails in the comet assay and the increase in the
number of TUNEL-positive cells. Subsequently, curcumin treatment caused a
significant accumulation of cells at the G2/M phase that eventually resulted in a
caspase-dependent apoptosis in BCPAP cells. DNA agarose gel electrophoresis
revealed that curcumin-induced DNA damage in BCPAP cells was independent of DNA
conformational change. Pretreatment with reactive oxygen species (ROS) scavengers
failed to block the phosphorylation of H2A.X, suggesting the non-involvement of
ROS in curcumin-mediated DNA damage. Interestingly, ATM/ATR activation by
curcumin induced phosphorylation of Chk2 (Thr68) followed by that of Cdc25C
(Ser216) and Cdc2 (Tyr15), and Cyclin B1 accumulation. In addition, the ATM
specific inhibitor KU-55933 reversed curcumin-induced phosphorylation of H2A.X.
These results collectively show that curcumin treatment induced the DNA damage
response via triggering an ATM-activated Chk2-Cdc25C-Cdc2 signaling pathway.
These observations provide novel mechanisms and potential targets for the better
understanding of the anti-cancer mechanisms of curcumin.
PMID- 26442631
TI - Poly(vinyl alcohol)-Poly(ethylene glycol) Double-Network Hydrogel: A General
Approach to Shape Memory and Self-Healing Functionalities.
AB - A double-network polymer hydrogel composed of chemically cross-linked
poly(ethylene glycol) (PEG) and physically cross-linked poly(vinyl alcohol) (PVA)
was prepared. When the hydrogel (70 wt % of water) is subjected to
freezing/thawing treatment under strain, the enhanced physical network as a
result of crystallization of PVA chains can stabilize the hydrogel deformation
after removal of the external force at room temperature. Subsequent disruption of
the physical network of PVA by heating allows for the recovery of the initial
shape of the hydrogel. Moreover, the double-network hydrogel exhibits self
healing capability stemming from the physical network of PVA by virtue of the
extensive interchain hydrogen bonding between the hydroxyl side groups. This
study thus demonstrates a general approach to imparting both the shape memory and
self-healing properties to chemically cross-linked hydrogels that otherwise do
not have such functionalities. Moreover, by making use of the fixed hydrogel
elongation, the effect of anisotropy arising from chain orientation on the self
healing was also observed.
PMID- 26442632
TI - New insights on the wooden weapons from the Paleolithic site of Schoningen.
AB - The Paleolithic site of Schoningen is famous for the earliest known, completely
preserved wooden weapons. Here we present recent results of an ongoing analysis
of the nine spears, one lance, a double pointed stick, and a burnt stick dating
to the Holsteinian, c. 300 kyr. Macroscopic and microscopic analyses, as well as
studies of thin sections, contribute to a better understanding of the manufacture
of the wooden weapons. They were deposited in organic sediments at a former
lakeshore among numerous bones of butchered horses. In general, the spears are
extremely well-preserved and show no or little sign of taphonomic alteration,
although some of the weapons are broken and parts were slightly moved, probably
by water action. The excellent preservation conditions provide considerable
information on the operational sequence of production. The hunters selected thin
trunks of spruce or pine and initially stripped off the bark. Traces of cutting,
scraping, and smoothing can be observed on the spear surfaces in detail. In the
case of spear X, repeated use of the weapon is implied by re-sharpening of the
tip. Analyses of wood anatomy provide information on climatic conditions and
contribute to the better understanding of the development of the site.
PMID- 26442634
TI - Sudomotor and vasomotor activity during the menstrual cycle with global heating.
AB - Many studies have reported that there are changes in sympathetic activity
throughout the menstrual cycle as there are oestrogen receptor in the
hypothalamus and all other parts of the sympathetic nervous system. The purpose
of this study was to see whether there were variations in sympathetic activity,
skin vasomotor and sweat gland sudomotor rhythms during the menstrual cycle.
Eight young female subjects with a regular menstrual cycle participated in the
study. Subjects were tested once during the follicular phase and once during the
luteal phase. Skin blood flow and sweat rate were significantly higher in the
luteal phase compared with the follicular phase (p < .05), but the frequency and
magnitude of sudomotor and vasomotor rhythms were significantly greater in the
follicular phase (p < .05). In contrast, spectral data showed less sympathetic
activity in the luteal phase. A significant finding here is that the sudomotor
rhythm of sweat glands is altered by the menstrual cycle.
PMID- 26442633
TI - Tolerance and reward equity predict cooperation in ravens (Corvus corax).
AB - Cooperative decision rules have so far been shown experimentally mainly in mammal
species that have variable and complex social networks. However, these traits
should not necessarily be restricted to mammals. Therefore, we tested cooperative
problem solving in ravens. We showed that, without training, nine ravens
spontaneously cooperated in a loose-string task. Corroborating findings in
several species, ravens' cooperative success increased with increasing inter
individual tolerance levels. Importantly, we found this in both a forced dyadic
setting, and in a group setting where individuals had an open choice to cooperate
with whomever. The ravens, moreover, also paid attention to the resulting reward
distribution and ceased cooperation when being cheated upon. Nevertheless, the
ravens did not seem to pay attention to the behavior of their partners while
cooperating, and future research should reveal whether this is task specific or a
general pattern. Given their natural propensity to cooperate and the results we
present here, we consider ravens as an interesting model species to study the
evolution of, and the mechanisms underlying cooperation.
PMID- 26442635
TI - Mobility behaviour and driving status of patients with mental disorders - an
exploratory study.
AB - BACKGROUND: Driving is an important activity of daily life and an integral part
of mobility. However, impact of mental illness on road mobility is widely
unexplored. METHOD: Driving status in 1497 psychiatric inpatients (PPs) and a
clinical control group of 313 neurological inpatients (NPs) was investigated
using a brief questionnaire. RESULTS: 67% of PPs (89% NPs) reported to have a
valid driver's licence and 77% of them (92% NPs) reported to regularly use their
cars. Within driver's license holders, patients with organic mental disorder
(32%), substance dependence (37%) and psychotic disorder (40%) had the lowest
proportion of current drivers. Higher educational qualification (odds ratio [OR]
from 2.978 to 17.036) and being married/partnered (OR 3.049) or divorced (OR
4.840) significantly advanced the probability of possession of a driving license.
Predictive factors for driving cessation were being female, an older age, drawing
a pension and having an organic mental disease or schizophrenic disorder.
CONCLUSION: Mental disease has a negative impact on driving status and this is
especially true for illnesses frequently being accompanied by distinct cognitive
impairments. Factors predicting road mobility elucidate the strong relationship
with psychosocial status indicating that recovery of driving competence should be
an integral goal of treatment strategies.
PMID- 26442636
TI - Macrophage-Associated Osteoactivin/GPNMB Mediates Mesenchymal Stem Cell Survival,
Proliferation, and Migration Via a CD44-Dependent Mechanism.
AB - Although MSCs have been widely recognized to have therapeutic potential in the
repair of injured or diseased tissues, it remains unclear how functional
activities of mesenchymal stem cells (MSCs) are influenced by the surrounding
inflammatory milieu at the site of tissue injury. Macrophages constitute an
essential component of innate immunity and have been shown to exhibit a
phenotypic plasticity in response to various stimuli, which play a central role
in both acute inflammation and wound repair. Osteoactivin (OA)/Glycoprotein non
metastatic melanoma protein B (GPNMB), a transmembrane glycoprotein that plays a
role in cell differentiation, survival, and angiogenesis. The objective of this
study was to investigate the potential role of OA/GPNMB in macrophage-induced MSC
function. We found that reparative M2 macrophages express significantly greater
levels of OA/GPNMB than pro-inflammatory M1 macrophages. Furthermore, using loss
of function and rescue studies, we demonstrated that M2 macrophages-secreted
OA/GPNMB positively regulates the viability, proliferation, and migration of
MSCs. More importantly, we demonstrated that OA/GPNMB acts through ERK and AKT
signaling pathways in MSCs via CD44, to induce these effects. Taken together, our
results provide pivotal insight into the mechanism by which OA/GPNMB contributes
to the tissue reparative phenotype of M2 macrophages and positively regulates
functional activities of MSCs. J. Cell. Biochem. 117: 1511-1521, 2016. (c) 2015
Wiley Periodicals, Inc.
PMID- 26442637
TI - Spatial nitrifications of microbial processes during composting of swine, cow and
chicken manure.
AB - Composting is a widely-used method to recycle the nutrients in livestock manure
for agriculture. The spatial stratifications of microbial processes inside the
manure particle that determine organic and nitrogen transformation are virtually
unclear. Here, we show the evolution of the interior microenvironment of swine,
cow and chicken manure by using microelectrodes during forced-aeration
composting. Composting has generally been regarded as an aerobic bioprocess,
however, the long-existing of a large anoxic zone inside these manures was
confirmed during the active phase in this study. The profile of the oxidation
reduction potential dramatically decreased first and then gradually increased.
The spatial difference in the ammonia concentration was not significant, but
nitrate concentration continuously decreased with depth. The anoxic condition
within the manure particle was demonstrated to be a primary cause of the severe
ammonia emission and the long composting period. These founding provided a new
insight toward "aerobic" composting process and a sound foundation for the
development of efficient composting technology.
PMID- 26442638
TI - Human genetics: Strength in numbers in the low-frequency spectrum.
PMID- 26442641
TI - Examining sludge production in bioelectrochemical systems treating domestic
wastewater.
AB - Sludge production in microbial bioelectrochemical systems (BES) was assessed in
conjunction with anaerobic and aerobic control reactors. Effluent after primary
settling tank (EAPS) and depleted EAPS spiked with acetate were treated. The
reactors were loaded with total suspended solids (TSS) and chemical oxygen demand
(COD) at average loading rates of 22 mg TSS d(-1)L(-1) and 86 mg COD d(-1)L(-1),
respectively. Carbon cloth anode equipped BES reactors delivered the highest
performance. They achieved on average a COD removal of 80%, a Coulomb efficiency
of 77% for EAPS, a maximum current density of 39 MUA cm(-)(3)/175 MUA cm(-)(2)
for EAPS and a TSS removal of 59%, yielding a sludge production of only 80 mg TSS
per g DeltaCOD. This study provides further evidence that BES can improve the
economics of wastewater treatment via lower sludge production as well as
providing a framework for understanding sludge production in BES.
PMID- 26442639
TI - Random monoallelic expression of autosomal genes: stochastic transcription and
allele-level regulation.
AB - Random monoallelic expression (RME) of genes represents a striking example of how
stochastic molecular processes can result in cellular heterogeneity. Recent
transcriptome-wide studies have revealed both mitotically stable and cell-to-cell
dynamic forms of autosomal RME, with the latter presumably resulting from burst
like stochastic transcription. Here, we discuss the distinguishing features of
these two forms of RME and revisit literature on their nature, pervasiveness and
regulation. Finally, we explore how RME may contribute to phenotypic variation,
including the incomplete penetrance and variable expressivity often seen in
genetic disease.
PMID- 26442640
TI - Genetic variation and the de novo assembly of human genomes.
AB - The discovery of genetic variation and the assembly of genome sequences are both
inextricably linked to advances in DNA-sequencing technology. Short-read
massively parallel sequencing has revolutionized our ability to discover genetic
variation but is insufficient to generate high-quality genome assemblies or
resolve most structural variation. Full resolution of variation is only
guaranteed by complete de novo assembly of a genome. Here, we review approaches
to genome assembly, the nature of gaps or missing sequences, and biases in the
assembly process. We describe the challenges of generating a complete de novo
genome assembly using current technologies and the impact that being able to
perfectly sequence the genome would have on understanding human disease and
evolution. Finally, we summarize recent technological advances that improve both
contiguity and accuracy and emphasize the importance of complete de novo assembly
as opposed to read mapping as the primary means to understanding the full range
of human genetic variation.
PMID- 26442643
TI - Erratum.
PMID- 26442642
TI - A fluorescent probe for specific detection of cysteine in the lipid dense region
of cells.
AB - A new cysteine (Cys) specific chemodosimetric reagent () is used in imaging of
endogenous Cys localized in the lipid dense region of the live Hct116 cells and
the release of Cys within HepG2 cells from a drug following a biochemical
transformation. A silica surface, modified with , could be used for quantitative
estimation of Cys present in aqueous solution (pH 7.2) and in a human blood
plasma (HBP).
PMID- 26442644
TI - Caregiver resilience in palliative care: a research protocol.
AB - AIM: To describe a research protocol designed to formulate a conceptual framework
of informal caregiver resilience in palliative care. BACKGROUND: Resilience is
the ability to adapt or to improve one's own conditions following experiences of
adversity. The end-of-life care provided by informal caregivers is a form of
adversity because it entails objective difficulties, emotional involvement and
deep levels of introspection that have been stimulated by the death event.
Resilience has not yet been addressed in association with end-of-life care.
DESIGN: This is a multicentre cross-sectional study. METHODS: We will administer
a questionnaire to a sample of informal end-of-life caregivers to collect data
about the main psychological, behavioural and healthcare factors that impact
resilience. Data analysis will include descriptive and correlational statistical
techniques, multiple linear regressions and structural equation modelling. Data
will be collected in multiple palliative care centres and statistical analysis
will be carried out using software: SPSS version 19.0 and MPlus version 7.3. The
study is supported by a grant from the Centre of Excellence for Nursing
Scholarship in Italy (Research Grant number 2.13.10) that was awarded in March
2013. DISCUSSION: The study seeks to identify the predictive, mediating and
moderating roles of select variables: caregivers' self-efficacy, burdens of
caregiving, depression and resilience. The results of this analysis will impact
the theoretical study of resilience in palliative care and will have practical
implications for interventions aimed at supporting caregivers through healthcare
teams.
PMID- 26442645
TI - Biomedical applications of nano-titania in theranostics and photodynamic therapy.
AB - Titanium dioxide (TiO2) is one of the most abundantly used nanomaterials for
human life. It is used in sunscreen, photovoltaic devices, biomedical
applications and as a food additive and environmental scavenger. Nano-TiO2 in
biomedical applications is well documented. It is used in endoprosthetic implants
and early theranostics of neoplastic and non-neoplastic maladies as a
photodynamic therapeutic agent and as vehicles in nano-drug delivery systems.
Herein, we focus on the recent advancements and applications of nano-TiO2 in bio
nanotechnology, nanomedicine and photodynamic therapy (PDT).
PMID- 26442646
TI - Warming decreased and grazing increased plant uptake of amino acids in an alpine
meadow.
AB - Organic nitrogen (N) uptake by plants has been recognized as a significant
component of terrestrial N cycle. Several studies indicated that plants have the
ability to switch their preference between inorganic and organic forms of N in
diverse environments; however, research on plant community response in organic
nitrogen uptake to warming and grazing is scarce. Here, we demonstrated that
organic N uptake by an alpine plant community decreased under warming with (13)C
(15)N-enriched glycine addition method. After 6 years of treatment, warming
decreased plant organic N uptake by 37% as compared to control treatment. Under
the condition of grazing, warming reduced plant organic N uptake by 44%. Grazing
alone significantly increased organic N absorption by 15%, whereas under warming
condition grazing did not affect organic N uptake by the Kobresia humilis
community on Tibetan Plateau. Besides, soil NO 3-N content explained more than
70% of the variability observed in glycine uptake, and C:N ratio in soil
dissolved organic matter remarkably increased under warming treatment. These
results suggested warming promoted soil microbial activity and dissolved organic
N mineralization. Grazing stimulated organic N uptake by plants, which
counteracted the effect of warming.
PMID- 26442647
TI - Empathy from the client's perspective: A grounded theory analysis.
AB - : Although empathy is one of most robust predictors of client outcome, there is
little consensus about how best to conceptualize this construct. OBJECTIVE: The
aim of the present research was to investigate clients' perceptions and in
session experiences of empathy. METHOD: Semi-structured, video-assisted
interpersonal process recall interviews were used to collect data from nine
clients receiving individual psychotherapy at a university psychology clinic.
RESULTS: Grounded theory analysis yielded a model consisting of three clusters:
(1) relational context of empathy (i.e., personal relationship and professional
relationship), (2) types of empathy (i.e., psychotherapists' cognitive empathy,
psychotherapists' emotional empathy, and client attunement to psychotherapist),
and (3) utility of empathy (i.e., process-related benefits and client-related
benefits). CONCLUSIONS: These results suggest that empathy is a multi
dimensional, interactional process that affects-and is affected by-the broader
relationship between client and psychotherapist.
PMID- 26442648
TI - Incidence of alloantibody formation after ABO-D or extended matched red blood
cell transfusions: a randomized trial (MATCH study).
AB - BACKGROUND: Most incidentally transfused patients receive only ABO-D-compatible
transfusions and antibodies are formed in up to 8%. The effect of extended (c, C,
E, K, Fy(a) , Jk(a) , and S antigens) matched (EM) and ABO-D-matched red blood
cell (RBC) transfusions on the incidence of new clinically relevant RBC antibody
formation after a first elective transfusion event in surgical patients was
studied. STUDY DESIGN AND METHODS: A multicenter randomized trial was performed
in nontransfused patients who were scheduled to experience a single elective
transfusion event of maximal 4 RBC units. The primary outcome was the incidence
of newly formed warm reacting clinically relevant RBC alloantibodies measured in
three follow-up (FU) samples taken at 7 to 10 days, 4 to 6 weeks, and 4 to 6
months posttransfusion. RESULTS: A total of 853 patients were randomized, and of
these, 333 patients were transfused with a total of 1035 RBC units. At least one
FU sample was available from 97% of transfused patients. In intention-to-treat
analysis, new antibodies were detected in 10 of 155 ABO-D and seven of 178 EM
patients, respectively. Per-protocol analysis including 190 patients showed a
nonsignificant absolute risk difference (ARD) of 5.3% (95% confidence interval
[CI], -1.4% to 12%) in alloimmunization between study arms. In a post hoc
analysis of 138 patients who received RBCs but no platelet (PLT) transfusions the
ARD increased to significance, 8.0% (95% CI, 0.4-16.0). CONCLUSION: Extended
matching for selected antigens reduced the alloimmunization risk by 64% in
surgical patients. Extended matching seems successful only if the patient did not
receive accompanying nonmatched PLT transfusions.
PMID- 26442650
TI - Prostate-specific antigen doubling time and response to cabazitaxel in a hormone
resistant metastatic prostate cancer patient.
AB - We report a case of metastatic castration-resistant prostate cancer, who received
prior treatment with docetaxel and was then given cabazitaxel as salvage therapy.
The patient was monitored by prostate-specific antigen doubling time and prostate
specific antigen absolute value. The prostate-specific antigen doubling time was
found to be a good response predictor in the patient.
PMID- 26442649
TI - Increasing interest in rural mental health work: the impact of a short term
program to orientate allied health and nursing students to employment and career
opportunities in a rural setting.
AB - INTRODUCTION: Ongoing workforce shortages affect the provision of mental health
services to rural and remote communities. This article examines the immediate
impact of a novel recruitment strategy that aims to increase the number of mental
health professionals commencing their careers in a rural area of Australia.
METHODS: This study utilised a sequential confirmatory mixed methods design which
included both online pre- and post-program surveys and semi-structured individual
interviews. Statistical analyses compared participants' pre- and post-program
survey interest in rural work/career, mental health work/career and rural mental
health work/career. Content analysis was undertaken to explore interview
transcripts for data that confirmed, contradicted or added depth to the
quantitative findings. RESULTS: Comparison of pre- and post-program surveys
indicated a significant increase in participants' interest in rural work/career
and rural mental health work/career. The qualitative findings provided depth to
and supported the change in interest toward working in a rural environment.
Despite qualitative evidence that the program has increased participants'
knowledge and understanding of the mental health sector as a whole, overt support
for the changes in interest toward mental health work was not evident.
CONCLUSIONS: The study provides evidence that a short-term program can change
allied health and nursing students' interest in rural mental health work. The
findings have important implications for the recruitment of mental health
practitioners to underserved rural areas.
PMID- 26442652
TI - Abstracts of the Joint Annual Conference of the International Society for
Pediatric and Adolescent Diabetes and Australasian Paediatric Endocrine Group
(ISPAD+APEG 2015), 7-10 October 2015, Brisbane, Australia.
PMID- 26442651
TI - The application of terminomics for the identification of protein start sites and
proteoforms in bacteria.
AB - Protein terminomics, or the study of amino acids sequences at the protein amino
or carboxyl terminus has rapidly evolved as a proteomic discipline due to
significant methodological improvements in the labelling and recovery of terminal
peptides as well as the increased speed and sensitivity of current mass
spectrometry instrumentation. The most significant beneficiaries of these
developments include an increased awareness and understanding of complex
proteolytic cascades that regulate key biological processes and in genome
annotation. Most terminomics research to date has focused on gaining insight into
important biological processes such as inflammation, wound healing and cancer.
The application of terminomics to the study of important biological questions in
prokaryotes is gaining traction. Here we review current applications and progress
of terminomics in prokaryotes, discuss the significance of protease research in
bacterial pathogenesis and protein maturation, and suggest novel applications of
terminomics in the study of infectious disease.
PMID- 26442653
TI - Electrochemical Fluorographane: Hybrid Electrocatalysis of Biomarkers, Hydrogen
Evolution, and Oxygen Reduction.
AB - Fluorographane (C1 Hx F1-x+delta )n is a new member of the graphene family that
exhibits hydrophobicity and a large band gap that is tunable based on the level
of fluorination. Herein, sensing and energy applications of fluorographane are
reported. The results reveal that the carbon-to-fluoride ratio of fluorographane
has a great impact on the electrochemical performance of the materials. Lowered
oxidation potentials for ascorbic and uric acids, in addition to a catalytic
effect for hydroquinone and dopamine redox processes, are obtained with a high
fluoride content. Moreover, fluorographane, together with residual copper- and
nickel-based doping, acted as a hybrid electrocatalyst to promote hydrogen
evolution and oxygen reduction reactions with considerably lower onset potentials
than those of graphane (starting material), which makes this a promising material
for a broad range of applications.
PMID- 26442654
TI - Development of a novel recessive genetic male sterility system for hybrid seed
production in maize and other cross-pollinating crops.
AB - We have developed a novel hybridization platform that utilizes nuclear male
sterility to produce hybrids in maize and other cross-pollinating crops. A key
component of this platform is a process termed Seed Production Technology (SPT).
This process incorporates a transgenic SPT maintainer line capable of propagating
nontransgenic nuclear male-sterile lines for use as female parents in hybrid
production. The maize SPT maintainer line is a homozygous recessive male sterile
transformed with a SPT construct containing (i) a complementary wild-type male
fertility gene to restore fertility, (ii) an alpha-amylase gene to disrupt
pollination and (iii) a seed colour marker gene. The sporophytic wild-type allele
complements the recessive mutation, enabling the development of pollen grains,
all of which carry the recessive allele but with only half carrying the SPT
transgenes. Pollen grains with the SPT transgenes exhibit starch depletion
resulting from expression of alpha-amylase and are unable to germinate. Pollen
grains that do not carry the SPT transgenes are nontransgenic and are able to
fertilize homozygous mutant plants, resulting in nontransgenic male-sterile
progeny for use as female parents. Because transgenic SPT maintainer seeds
express a red fluorescent protein, they can be detected and efficiently separated
from seeds that do not contain the SPT transgenes by mechanical colour sorting.
The SPT process has the potential to replace current approaches to pollen control
in commercial maize hybrid seed production. It also has important applications
for other cross-pollinating crops where it can unlock the potential for greater
hybrid productivity through expanding the parental germplasm pool.
PMID- 26442655
TI - Long-term spatiotemporal stability and dynamic changes in helminth
infracommunities of bank voles (Myodes glareolus) in NE Poland.
AB - Parasites are considered to be an important selective force in host evolution but
ecological studies of host-parasite systems are usually short-term providing only
snap-shots of what may be dynamic systems. We have conducted four surveys of
helminths of bank voles at three ecologically similar woodland sites in NE
Poland, spaced over a period of 11 years, to assess the relative importance of
temporal and spatial effects on helminth infracommunities. Some measures of
infracommunity structure maintained relative stability: the rank order of
prevalence and abundance of Heligmosomum mixtum, Heligmosomoides glareoli and
Mastophorus muris changed little between the four surveys. Other measures changed
markedly: dynamic changes were evident in Syphacia petrusewiczi which declined to
local extinction, while the capillariid Aonchotheca annulosa first appeared in
2002 and then increased in prevalence and abundance over the remaining three
surveys. Some species are therefore dynamic and both introductions and
extinctions can be expected in ecological time. At higher taxonomic levels and
for derived measures, year and host-age effects and their interactions with site
are important. Our surveys emphasize that the site of capture is the major
determinant of the species contributing to helminth community structure,
providing some predictability in these systems.
PMID- 26442656
TI - [Evolution of the interventional reperfusion strategy and reperfusion times in
acute ST-segment elevation myocardial infarction].
AB - BACKGROUND: In patients with acute ST-segment elevation myocardial infarction
(STEMI) treated with primary percutaneous coronary intervention (pPCI), the
recommended times (first medical contact-to-balloon (M2B) <120 or <90min, and
door-to-balloon (D2B) <45min) are reached in less than 50% of patients. PURPOSE:
To compare the interventional reperfusion strategy and reperfusion times between
two series of consecutive STEMI patients referred for pPCI within 12hours of
symptom onset, in 2007 and 2012. METHODS: Retrospective study of 182 patients, 87
admitted from January 2007 to March 2008 (period 1), and 95 admitted from January
to December 2012 (period 2). The procedural characteristics and the different
times between onset of pain and mechanical reperfusion were gathered and compared
by non-parametric tests. RESULTS: Radial access, thromboaspiration, and drug
eluting stents were more frequent, and cardiogenic shock was less common during
period 2, compared with the period 1. The median time from first medical contact
to balloon (M2B) decreased by 26% (135min, [quartiles: 113-183] in 2007 versus
100 [76-137] in 2012, P<0.001), in relation to the reduction in both prehospital
times and time in the catheterization laboratory (D2B: 51 [44-65] and 44min [37
55], respectively, P<0.01). CONCLUSIONS: The D2B and M2B times significantly
decreased in our centre between 2007 and 2012, and reached the recommended values
in >60% of the cases. This may be explained by better coordination between
emergency medical units and interventional cardiologists, and by the presence of
two paramedics in the catheterization laboratory for 24/24 7/7 pPCI since 2010 in
France, in accordance with recent national regulation.
PMID- 26442657
TI - MyD88 in donor bone marrow cells is critical for protection from acute intestinal
graft-vs.-host disease.
AB - To understand the role of myeloid differentiation factor 88 (MyD88) expressed by
donor bone marrow (BM) in the pathophysiology of graft-vs.-host disease (GVHD),
we investigated the effects of transplantation of MyD88-deficient T cell-depleted
BM (MyD88KO TCD-BM) on the severity of GVHD. Transplantation with MyD88KO TCD-BM
aggravated GVHD; serious gut damage was evident, with high infiltration of T
cells into the intestines of recipients and markedly reduced expansion of
CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). MDSCs from MyD88KO mice
were defective in inducing donor T-cell apoptosis and inhibiting T-cell
proliferation. Supplementation of transplanted mice with MDSCs from wild-type
mice, but not MyD88KO mice, attenuated GVHD severity with reduced intestinal T
cell infiltration in MyD88KO TCD-BM recipients. Pretreatment of BM donors with
lipopolysaccharide to increase MDSC levels and MyD88 transcription in the TCD-BM
transplant alleviated GVHD severity and intestinal T-cell infiltration. The T
cell/MDSC ratios were correlated with intestinal GVHD severity in both animal
models and human patients. This study indicates that MyD88-dependent MDSC
expansion from donor BM is critical for protection against fatal intestinal GVHD.
PMID- 26442658
TI - Role of mannose-binding lectin in intestinal homeostasis and fungal elimination.
AB - Mannose-binding lectin (MBL) is a soluble lectin of the innate immune system that
is produced by the liver and secreted into the circulation where it activates the
lectin complement pathway, enhances phagocytosis of microorganisms by leukocytes,
and modulates inflammation. MBL can recognize patterns on the surface of
different pathogens, including Candida albicans. Our aims were to investigate
whether MBL is expressed in the gut epithelium and to examine its effect on the
modulation of intestinal inflammation and C. albicans elimination. Using reverse
transcriptase-PCR, MBL transcripts were highly expressed in different parts of
the mouse gut. MBL expression was also detected by immunoblotting and
immunolocalization in response to C. albicans colonization of the gut; the
highest expression of MBL was detected in the stomach. Blocking MBL by
administering mannans to mice increased C. albicans colonization. MBL-deficient
mice had a higher level of colonization than wild-type mice. Dextran sodium
sulfate-induced colitis promoted C. albicans dissemination to the kidneys and
lungs of MBL-deficient mice. MBL-deficient mice exhibited elevated expression of
interleukin (IL)-17, IL-23, dectin-1, and Toll-like receptor-4. This study shows
that MBL expression is induced in the gut in response to C. albicans sensing and
is required for intestinal homeostasis and host defense against C. albicans.
PMID- 26442661
TI - Influence of caffeine on 3,4-methylenedioxymethamphetamine-induced dopaminergic
neuron degeneration and neuroinflammation is age-dependent.
AB - Previous studies have demonstrated that caffeine administration to adult mice
potentiates glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA).
As neuroinflammatory response seems to correlate with neurodegeneration, and the
young brain is particularly vulnerable to neurotoxicity, we evaluated dopamine
neuron degeneration and glial activation in the caudate-putamen (CPu) and
substantia nigra pars compacta (SNc) of adolescent and adult mice. Mice were
treated with MDMA (4 * 20 mg/kg), alone or with caffeine (10 mg/kg). Interleukin
(IL)-1beta, tumor necrosis factor (TNF)-alpha, neuronal nitric oxide synthase
(nNOS) were evaluated in CPu, whereas tyrosine hydroxylase (TH), glial fibrillary
acidic protein, and CD11b were evaluated in CPu and SNc by immunohistochemistry.
MDMA decreased TH in SNc of both adolescent and adult mice, whereas TH-positive
fibers in CPu were only decreased in adults. In CPu of adolescent mice, caffeine
potentiated MDMA-induced glial fibrillary acidic protein without altering CD11b,
whereas in SNc caffeine did not influence MDMA-induced glial activation. nNOS, IL
1beta, and TNF-alpha were increased by MDMA in CPu of adults, whereas in
adolescents, levels were only elevated after combined MDMA plus caffeine.
Caffeine alone modified only nNOS. Results suggest that the use of MDMA in
association with caffeine during adolescence may exacerbate the neurotoxicity and
neuroinflammation elicited by MDMA. Previous studies have demonstrated that
caffeine potentiated glial activation induced by 3,4
methylenedioxymethamphetamine (MDMA) in adult mice. In this study, caffeine was
shown to potentiate MDMA-induced dopamine neuron degeneration in substantia nigra
pars compacta, astrogliosis, and TNF-alpha levels in caudate-putamen of
adolescent mice. Results suggest that combined use of MDMA plus caffeine during
adolescence may worsen the neurotoxicity and neuroinflammation elicited by MDMA.
PMID- 26442659
TI - Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive
soluble guanylate cyclase knock-in mice.
AB - Oxidative stress, a central mediator of cardiovascular disease, results in loss
of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its
activation by nitric oxide (NO). Here we introduce Apo-sGC mice expressing haem
free sGC. Apo-sGC mice are viable and develop hypertension. The haemodynamic
effects of NO are abolished, but those of the sGC activator cinaciguat are
enhanced in apo-sGC mice, suggesting that the effects of NO on smooth muscle
relaxation, blood pressure regulation and inhibition of platelet aggregation
require sGC activation by NO. Tumour necrosis factor (TNF)-induced hypotension
and mortality are preserved in apo-sGC mice, indicating that pathways other than
sGC signalling mediate the cardiovascular collapse in shock. Apo-sGC mice allow
for differentiation between sGC-dependent and -independent NO effects and between
haem-dependent and -independent sGC effects. Apo-sGC mice represent a unique
experimental platform to study the in vivo consequences of sGC oxidation and the
therapeutic potential of sGC activators.
PMID- 26442662
TI - Low expression of IL-6 and TNF-alpha correlates with the presence of the nuclear
regulators of NF-kappaB, IkappaBNS and BCL-3, in the uterus of mice.
AB - The dynamic regulation of NF-kappaB activity in the uterus maintains a favorable
environment of cytokines necessary to prepare for pregnancy throughout the
estrous cycle. Recently, the mechanisms that directly regulate the NF-kappaB
transcriptional activity in different tissues are of growing interest. IkappaBNS
and BCL-3 are negative nuclear regulators of NF-kappaB activity that regulate IL
6 and TNF-alpha transcription, respectively. Both cytokines have been described
as important factors in the remodeling of uterus for blastocyst implantation. In
this work we analyzed in ICR mice the mRNA expression and protein production
profile of IL-6, TNF-alpha, and their correspondent negative transcription
regulators IkappaBNS or BCL-3 using real-time PCR, western blot and
immunochemistry. We found that the expression of TNF-alpha and IL-6 was
oscillatory along the estrous cycle, and its low expression coincided with the
presence of BCL-3 and IkappaBNS, and vice versa, when the presence of the
regulators was subtle, the expression of TNF-alpha and IL-6 was exacerbated. When
we compared the production of TNF-alpha and IL-6 in the different estrous stages
relating with diestrus we found that at estrus there is an important increase of
the cytokines (p<0.05) decreasing at metestrus to reach the basal expression at
diestrus. In the immunochemistry analysis we found that at diestrus BCL-3 is
distributed all over the tissue with a barely detected TNF-alpha, but on the
contrary, at estrus the expression of BCL-3 is not detected with TNF-alpha
clearly observable along the tissue; the same phenomenon occur in the analysis of
IkappaBNS and IL-6. With that evidence we suggest that the expression of TNF
alpha and IL-6 might be regulated through NF-kappaB nuclear regulators BCL-3 and
IkappaBNS in the uterus of mice as has been demonstrated in other systems.
PMID- 26442663
TI - Endogenous galectin-3 expression levels modulate immune responses in galectin-3
transgenic mice.
AB - Galectin-3 (Gal-3), a beta-galactoside-binding mammalian lectin, is involved in
cancer progression and metastasis. However, there is an unmet need to identify
the underlying mechanisms of cancer metastasis mediated by endogenous host
galectin-3. Galectin-3 is also known to be an important regulator of immune
responses. The present study was aimed at analysing how expression of endogenous
galectin-3 regulates host immunity and lung metastasis in B16F10 murine melanoma
model. Transgenic Gal-3(+/-) (hemizygous) and Gal-3(-/-) (null) mice exhibited
decreased levels of Natural Killer (NK) cells and lower NK mediated cytotoxicity
against YAC-1 tumor targets, compared to Gal-3(+/+) (wild-type) mice. On
stimulation, Gal-3(+/-) and Gal-3(-/-) mice splenocytes showed increased T cell
proliferation than Gal-3(+/+) mice. Intracellular calcium flux was found to be
lower in activated T cells of Gal-3(-/-) mice as compared to T cells from Gal
3(+/+) and Gal-3(+/-) mice. In Gal-3(-/-) mice, serum Th1, Th2 and Th17 cytokine
levels were found to be lowest, exhibiting dysregulation of pro-inflammatory and
anti-inflammatory cytokines balance. Marked decrease in serum IFN-gamma levels
and splenic IFN-gammaR1 (IFN-gamma Receptor 1) expressing T and NK cell
percentages were observed in Gal-3(-/-) mice. On recombinant IFN-gamma treatment
of splenocytes in vitro, Suppressor of Cytokine Signaling (SOCS) 1 and SOCS3
protein expression was higher in Gal-3(-/-) mice compared to that in Gal-3(+/+)
and Gal-3(+/-) mice; suggesting possible attenuation of Signal Transducer and
Activator of Transcription (STAT) 1 mediated IFN-gamma signaling in Gal-3(-/-)
mice. The ability of B16F10 melanoma cells to form metastatic colonies in the
lungs of Gal-3(+/+) and Gal-3(-/-) mice remained comparable, whereas it was found
to be reduced in Gal-3(+/-) mice. Our data indicates that complete absence of
endogenous host galectin-3 facilitates lung metastasis of B16F10 cells in mice,
which may be contributed by dysregulated immune responses resulting from
decreased NK cytotoxicity, disturbed serum Th1, Th2, Th17 cytokine milieu,
reduced serum IFN-gamma levels and attenuation of splenic STAT1 mediated IFN
gamma signalling in Gal-3(-/-) mice.
PMID- 26442664
TI - PLGA (85:15) nanoparticle based delivery of rL7/L12 ribosomal protein in mice
protects against Brucella abortus 544 infection: A promising alternate to
traditional adjuvants.
AB - There is a compelling need for the development of suitable adjuvants for human
use to enhance the efficacy of the upcoming vaccines for the prevention of life
threatening infections. In the current study, we have tried to explore the
immunogenic potential of nanoparticles (NPs) made of PLGA (poly lactic-co
glycolic acid), a biodegradable and biocompatible polymer approved by FDA for
human use after entrapping rL7/L12 protein, an immunodominant antigen of
Brucella. Adjuvant properties were exhibited by the formulation as it elicited
high IgG antibody titers just after first immunization which increased
significantly after the booster administration. A good elicitation of the Th1
cytokines especially IFN-gamma was recorded. Amongst the IgG antibody subclasses,
IgG1 remained the predominant subclass to be elicited in mice serum after
immunization; however IgG1/2a ratio showed a mixed profile of Th1/Th2 response.
Lymphocyte proliferation assay as a marker of amplification in cellular immunity
demonstrated that the splenocytes of the immunized mice had a high proliferation
index with reference to the control, revealing that L7/L12 entrapping PLGA
nanoparticles are potent inducer of inflammatory cell response indispensable to
combat Brucella infection. Enumeration of splenic CFU after 14 days of infection
with Brucella abortus 544 showed a significant reduction in log CFU of splenic
bacteria in the vaccinated mice as compared to the control group. Therefore it is
evident that PLGA nano formulations delivering the entrapped vaccine candidate in
mice elicit specific humoral as well as cellular responses specific to the
entrapped Brucella antigen. So there is much promise in this approach and this
work by highlighting the adjuvant properties of the PLGA nanospheres will
accelerate the development of improved vaccines safe for human as well as
veterinary use.
PMID- 26442665
TI - Spontaneous Facial Mimicry is Modulated by Joint Attention and Autistic Traits.
AB - Joint attention (JA) and spontaneous facial mimicry (SFM) are fundamental
processes in social interactions, and they are closely related to empathic
abilities. When tested independently, both of these processes have been usually
observed to be atypical in individuals with autism spectrum conditions (ASC).
However, it is not known how these processes interact with each other in relation
to autistic traits. This study addresses this question by testing the impact of
JA on SFM of happy faces using a truly interactive paradigm. Sixty-two
neurotypical participants engaged in gaze-based social interaction with an
anthropomorphic, gaze-contingent virtual agent. The agent either established JA
by initiating eye contact or looked away, before looking at an object and
expressing happiness or disgust. Eye tracking was used to make the agent's gaze
behavior and facial actions contingent to the participants' gaze. SFM of happy
expressions was measured by Electromyography (EMG) recording over the Zygomaticus
Major muscle. Results showed that JA augments SFM in individuals with low
compared with high autistic traits. These findings are in line with reports of
reduced impact of JA on action imitation in individuals with ASC. Moreover, they
suggest that investigating atypical interactions between empathic processes,
instead of testing these processes individually, might be crucial to
understanding the nature of social deficits in autism. Autism Res 2016, 9: 781
789. (c) 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on
behalf of International Society for Autism Research.
PMID- 26442666
TI - Brain substrates of social decision-making in dual diagnosis: cocaine dependence
and personality disorders.
AB - Cocaine dependence frequently co-occurs with personality disorders, leading to
increased interpersonal problems and greater burden of disease. Personality
disorders are characterised by patterns of thinking and feeling that divert from
social expectations. However, the comorbidity between cocaine dependence and
personality disorders has not been substantiated by measures of brain activation
during social decision-making. We applied functional magnetic resonance imaging
to compare brain activations evoked by a social decision-making task-the
Ultimatum Game-in 24 cocaine dependents with personality disorders (CDPD), 19
cocaine dependents without comorbidities and 19 healthy controls. In the
Ultimatum Game participants had to accept or reject bids made by another player
to split monetary stakes. Offers varied in fairness (in fair offers the proposer
shares ~50 percent of the money; in unfair offers the proposer shares <30 percent
of the money), and participants were told that if they accept both players get
the money, and if they reject both players lose it. We contrasted brain
activations during unfair versus fair offers and accept versus reject choices.
During evaluation of unfair offers CDPD displayed lower activation in the insula
and the anterior cingulate cortex and higher activation in the lateral
orbitofrontal cortex and superior frontal and temporal gyri. Frontal activations
negatively correlated with emotion recognition. During rejection of offers CDPD
displayed lower activation in the anterior cingulate cortex, striatum and
midbrain. Dual diagnosis is linked to hypo-activation of the insula and anterior
cingulate cortex and hyper-activation of frontal-temporal regions during social
decision-making, which associates with poorer emotion recognition.
PMID- 26442667
TI - Causal Inference in Developmental Origins of Health and Disease (DOHaD) Research.
AB - Studies of the developmental origins of health and disease (DOHaD) often rely on
prospective observational data, from which associations between developmental
exposures and outcomes in later life can be identified. Typically, conventional
statistical methods are used in an attempt to mitigate problems inherent in
observational data, such as confounding and reverse causality, but these have
serious limitations. In this review, we discuss a variety of methods that are
increasingly being used in observational epidemiological studies to help
strengthen causal inference. These methods include negative controls, cross
contextual designs, instrumental variables (including Mendelian randomization),
family-based studies, and natural experiments. Applications within the DOHaD
framework, and in relation to behavioral, psychiatric, and psychological domains,
are considered, and the considerable potential for expanding the use of these
methods is outlined.
PMID- 26442669
TI - Beyond Work-Life "Integration".
AB - Research on the work-family interface began in the 1960s and has grown
exponentially ever since. This vast amount of research, however, has had
relatively little impact on workplace practice, and work-family conflict is at an
all-time high. We review the work-family research to date and propose that a
shift of attention is required, away from the individual experience of work and
family and toward understanding how identity and status are defined at work.
Several factors enshrine cherished identities around current workplace norms. The
work devotion schema demands that those who are truly committed to their work
will make it the central or sole focus of their lives, without family demands to
distract them. Importantly, the work devotion schema underwrites valued class and
gender identities: Work devotion is a key way of enacting elite class status and
functions as the measure of a man--the longer the work hours and higher the
demand for his attention, the better. Advocating change in the way work is done
and life is lived meets resistance because it places these cherished identities
at risk. Resistance to these identity threats keeps current workplace norms in
place. This is why even the business case-which shows that current practices are
not economically efficient-fails to persuade organizations to enact change. What
is needed now is sustained attention to the implicit psychological infrastructure
that cements the mismatch between today's workplace and today's workforce.
PMID- 26442668
TI - Gene * Environment Determinants of Stress- and Anxiety-Related Disorders.
AB - The burgeoning field of gene-by-environment (G*E) interactions has revealed
fascinating biological insights, particularly in the realm of stress-, anxiety-,
and depression-related disorders. In this review we present an integrated view of
the study of G*E interactions in stress and anxiety disorders, including the
evolution of genetic association studies from genetic epidemiology to
contemporary large-scale genome-wide association studies and G*E studies. We
convey the importance of consortia efforts and collaboration to gain the large
sample sizes needed to move the field forward. Finally, we discuss several robust
and well-reproduced G*E interactions and demonstrate how epidemiological
identification of G*E interactions has naturally led to a plethora of basic
research elucidating the mechanisms of high-impact genetic variants.
PMID- 26442670
TI - Role of JAK-STAT signaling in maturation of phagosomes containing Staphylococcus
aureus.
AB - Phagocytosis is a required mechanism for the defense against pathogens.
Staphylococcus aureus, an important bacterial pathogen, can promptly escape from
phagosomes and proliferate within the cytoplasm of host. However, the mechanism
of phagocytosis against S. aureus has not been intensively investigated. In this
study, the S. aureus was engulfed by macrophages (RAW264.7 cells) but not
digested by the cells, suggesting that the phagosomes did not maturate in
macrophages. Further investigation revealed that peptidoglycan (PG) induced the
phagosome maturation of macrophages, resulting in the eradication of S. aureus.
Genome-wide analysis and quantitative real-time PCR indicated that the JAK-STAT
pathway was activated by PG during the phagosome maturation of macrophages
against S. aureus. This finding presented that the PG-activated JAK-STAT pathway
was required for phagosome maturation. Therefore, our study contributed evidence
that revealed a novel aspect of PG-triggered JAK-STAT pathway in the phagosome
maturation of macrophages.
PMID- 26442671
TI - Mapping the H(+) (V)-ATPase interactome: identification of proteins involved in
trafficking, folding, assembly and phosphorylation.
AB - V-ATPases (H(+) ATPases) are multisubunit, ATP-dependent proton pumps that
regulate pH homeostasis in virtually all eukaryotes. They are involved in key
cell biological processes including vesicle trafficking, endosomal pH sensing,
membrane fusion and intracellular signaling. They also have critical systemic
roles in renal acid excretion and blood pH balance, male fertility, bone
remodeling, synaptic transmission, olfaction and hearing. Furthermore, V-ATPase
dysfunction either results in or aggravates various other diseases, but little is
known about the complex protein interactions that regulate these varied V-ATPase
functions. Therefore, we performed a proteomic analysis to identify V-ATPase
associated proteins and construct a V-ATPase interactome. Our analysis using
kidney tissue revealed V-ATPase-associated protein clusters involved in protein
quality control, complex assembly and intracellular trafficking. ARHGEF7, DMXL1,
EZR, NCOA7, OXR1, RPS6KA3, SNX27 and 9 subunits of the chaperonin containing TCP1
complex (CCT) were found to interact with V-ATPase for the first time in this
study. Knockdown of two interacting proteins, DMXL1 and WDR7, inhibited V-ATPase
mediated intracellular vesicle acidification in a kidney cell line, providing
validation for the utility of our interactome as a screen for functionally
important novel V-ATPase-regulating proteins. Our data, therefore, provide new
insights and directions for the analysis of V-ATPase cell biology and
(patho)physiology.
PMID- 26442672
TI - Kv3.3 potassium channels and spinocerebellar ataxia.
AB - The voltage-dependent potassium channel subunit Kv3.3 is expressed at high levels
in cerebellar Purkinje cells, in auditory brainstem nuclei and in many other
neurons capable of firing at high rates. In the cerebellum, it helps to shape the
very characteristic complex spike of Purkinje cells. Kv3.3 differs from other
closely related channels in that human mutations in the gene encoding Kv3.3
(KCNC3) result in a unique neurodegenerative disease termed spinocerebellar
ataxia type 13 (SCA13). This primarily affects the cerebellum, but also results
in extracerebellar symptoms. Different mutations produce either early onset
SCA13, associated with delayed motor and impaired cognitive skill acquisition, or
late onset SCA13, which typically produces cerebellar degeneration in middle age.
This review covers the localization and physiological function of Kv3.3 in the
central nervous system and how the normal function of the channel is altered by
the disease-causing mutations. It also describes experimental approaches that are
being used to understand how Kv3.3 mutations are linked to neuronal survival, and
to develop strategies for treatment.
PMID- 26442673
TI - Conceptual Representation Changes in Indonesian-English Bilinguals.
AB - This study investigated conceptual representations changes in bilinguals.
Participants were Indonesian-English bilinguals (dominant in Indonesian, with
different levels of English proficiency) and a control group composed of English
dominant bilinguals. All completed a gender decision task, in which participants
decided whether English words referred to a male or female person or animal. In
order to explore conceptual representations, we divided the words into gender
specific and gender-ambiguous words. Gender-specific words were words in which
conceptual representations contained gender as a defining feature, in both
English and Indonesian (e.g., uncle). In contrast, gender-ambiguous words were
words in which gender was a defining feature in English but not a necessary
feature in Indonesian (e.g., nephew and niece are both subsumed under the same
word, keponakan, in Indonesian). The experiment was conducted exclusively in
English. Indonesian-English bilinguals responded faster to gender-specific words
than gender-ambiguous words, but the difference was smaller for the most
proficient bilinguals. As expected, English-dominant speakers' response latencies
were similar across these two types of words. The results suggest that English
concepts are dynamic and that proficiency leads to native-like conceptual
representations.
PMID- 26442674
TI - Cerebral insulin, insulin signaling pathway, and brain angiogenesis.
AB - Insulin performs unique non-metabolic functions within the brain. Broadly
speaking, two major areas of these functions are those related to brain
endothelial cells and the blood-brain barrier (BBB) function, and those related
to behavioral effects, like cognition in disease states (Alzheimer's disease, AD)
and in health. Recent studies showed that both these functions are associated
with brain angiogenesis. These findings raise interesting questions such as how
they are linked to each other and whether modifying brain angiogenesis by
targeting certain insulin signaling pathways could be an effective strategy to
treat dementia as in AD, or even to help secure healthy longevity. The two
canonical downstream pathways involved in mediating the insulin signaling
pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein
kinase (MAPK) cascades, in the brain are supposed to be similar to those in the
periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are
involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could
be activated by the insulin signaling pathway. This suggests that PI3K and MAPK
pathways might act as cross-talk between the insulin signaling pathway and the
angiogenesis pathway in brain. But the cerebral insulin, insulin signaling
pathway, and the detailed mechanism in the connection of insulin signaling
pathway, brain angiogenesis pathway, and healthy aging or dementias are still
mostly not clear and need further studies.
PMID- 26442675
TI - Faster and economical screening for vancomycin-resistant enterococci by
sequential use of chromogenic agar and real-time polymerase chain reaction.
AB - BACKGROUND/PURPOSE: Screening for vancomycin-resistant enterococci (VRE) by
culture takes days to generate results, while polymerase chain reaction (PCR)
testing directly from clinical specimens lacks specificity. The aims of this
study were to develop a real-time PCR to detect and identify Enterococcus
faecium, Enterococcus faecalis, and vanA and vanB genes, and to evaluate the
impact of this PCR on test-reporting times when performing it directly from
suspect VRE isolates present on screening chromogenic media. METHODS: The
tetraplex PCR primers were designed to amplify E. faecium, E. faecalis, and vanA
and vanB genes, with melt-curve analysis of PCR products. Following analytical
and clinical validation of the molecular assay, PCR testing was performed for
target colonies present on VRE chromogenic media. PCR results were evaluated
against conventional phenotypic identification and susceptibility testing, with
the time to result being monitored for both modalities. RESULTS: A total of 519
colonies from clinical specimens were tested concurrently by real-time PCR and
phenotypic methods. In all, 223 isolates were identified with phenotypic
vancomycin resistance (vanA, n = 108; vanB, n = 105; non-vanA/vanB = 10), with
complete agreement between PCR and phenotypic testing for vancomycin-resistant E.
faecium and E. faecalis. The majority (88.6%) of PCR results were reported, on
average, 24.8 hours earlier than those of phenotypic testing, with 68% reduction
in total costs. CONCLUSION: The use of culture on selective media, followed by
direct colony PCR confirmation allows faster and economical VRE screening.
PMID- 26442676
TI - Bloodstream infections in pediatric patients with acute leukemia: Emphasis on
gram-negative bacteria infections.
AB - BACKGROUND/PURPOSE: Acute leukemia is the most common pediatric hematological
malignancy. Bloodstream infections (BSIs) are severe complications in these
patients during chemotherapy. This study aims to explore clinical features,
laboratory, and microbiological characteristics of BSIs in acute leukemic
children. METHODS: Patients aged < 18 years, diagnosed with acute myeloid
leukemia or acute lymphocytic leukemia with BSIs from January 2004 to December
2013 were enrolled. BSIs was defined as positive isolate(s) of blood culture and
associated with clinical findings. Clinical presentations, demographic features,
and microbiological findings were retrospectively reviewed. RESULTS: In total,
126 isolates of 115 episodes of BSIs were identified from 69 patients (acute
lymphocytic leukemia 56; acute myeloid leukemia 13). Gram-negative bacteria
(GNB), gram-positive cocci, and fungi constituted 56.3%, 42.3%, and 2.4% of the
pathogens, respectively. Eighty-three and a half percent of BSIs occurred along
with neutropenia, and 73% had severe neutropenia. GNB was the leading pathogen of
BSIs. The major GNBs were Escherichia coli, Klebsiella pneumonia, and Pseudomonas
aeruginosa. White blood cell counts, absolute neutrophil counts, and platelet
counts were significantly lower in patients of BSIs caused by GNB than gram
positive cocci. Plasma level of C-reactive protein was significant high in
patients of GNB BSIs (179.8 mg/L vs. 127.2 mg/L; p = 0.005). Eighty-two percent
of patients of E. coli, K. pneumonia, and P. aeruginosa BSIs had sepsis related
organ failure or organ dysfunction. P. aeruginosa BSIs had the highest case
mortality (40%). CONCLUSION: Neutropenia was the major risk factor of BSIs in
pediatric leukemic patients. BSIs of GNB were associated with severe neutropenia,
systemic inflammatory responses, and high mortality.
PMID- 26442677
TI - Management of Retropharyngeal Node Metastases from Thyroid Carcinoma: Reply.
PMID- 26442678
TI - Incidence and predictors of myocardial recovery on long-term left ventricular
assist device support: Results from the United Network for Organ Sharing
database.
AB - BACKGROUND: Mechanical circulatory support (MCS) leads to favorable changes in
the failing heart at the molecular, cellular, and structural levels. However,
myocardial recovery leading to device explantation is rare. We reasoned that the
multicenter United Network for Organ Sharing (UNOS) registry might provide
insights into clinical predictors and outcomes of the recovery process. METHODS:
The MCS device data set of the UNOS registry was queried for patients with long
term continuous-flow left ventricular assist devices (CF-LVADs) that were
explanted for heart transplantation or indication of recovery. Analysis was
restricted to adult patients (>=18 years old) who were listed for an initial
heart transplantation. Patients with CF-LVADs that were explanted because of
recovery were compared with patients with CF-LVADs who underwent transplantation.
RESULTS: We identified 594 patients with HeartMate II devices and 92 patients
with HeartWare devices. Duration of support was on average 500.4 +/- 325.3 days.
In 34 (5.0%) patients, devices were explanted secondary to myocardial recovery.
Univariate predictors of recovery in patients with long-term LVADs included
younger age (40 years vs 53 years), female sex, lower body mass index (25.7
kg/m(2) vs 27.9 kg/m(2)), non-ischemic etiology (91% vs 59%), lack of implantable
cardioverter defibrillator at the time of listing (44% vs 79%), and lower serum
creatinine (0.97 mg/dl vs 1.28 mg/dl) (all p < 0.05). In the post-explantation
period, freedom from death or transplantation was 66% at 1 year. CONCLUSIONS: The
incidence of recovery on device support is low in the current MCS era and limited
to a select cohort of predominantly young patients with non-ischemic myopathy.
Given the high incidence of disease recurrence, patients should be closely
followed after device explantation.
PMID- 26442679
TI - Unique Aspects of Plant Nonsense-Mediated mRNA Decay.
AB - Nonsense-mediated mRNA Decay (NMD) is a eukaryotic quality-control mechanism that
governs the stability of both aberrant and normal transcripts. Although plant and
mammalian NMD share great similarity, they differ in certain mechanistic and
regulatory aspects. Whereas SMG6 (from Caenorhabditis elegans 'suppressor with
morphogenetic effect on genitalia')-catalyzed endonucleolytic cleavage is a
prominent step in mammalian NMD, plant NMD targets are degraded by an SMG7
induced exonucleolytic pathway. Both mammalian and plant NMD are downregulated by
stress, thereby enhancing the expression of defense response genes. However, the
target genes and processes affected differ. Several plant and mammalian NMD
factors are regulated by negative feedback-loops. However, while the loop
regulating UPF3 (up-frameshift 3) expression in not vital for mammalian NMD, the
sensitivity of UPF3 to NMD is crucial for the overall regulation of plant NMD.
PMID- 26442680
TI - Licensed to Kill: Mitochondria, Chloroplasts, and Cell Death.
AB - Programmed cell death (PCD) is crucial in plant organogenesis and survival. In
this review the involvement of mitochondria and chloroplasts in PCD execution is
critically assessed. Recent findings support a central role for mitochondria in
PCD, with newly identified components of the mitochondrial electron transport
chain (mETC), FOF1 ATP synthase, cardiolipins, and ATPase AtOM66. While
chloroplasts received less attention, their contribution to PCD is well
supported, suggesting that they possibly contribute by producing reactive oxygen
species (ROS) in the presence of light or even contribute through cytochrome f
release. Finally we discuss two working models where mitochondria and
chloroplasts could cooperatively execute PCD: mitochondria initiate the
commitment steps and recruit chloroplasts for swift execution or, alternatively,
mitochondria and chloroplasts could operate in parallel.
PMID- 26442681
TI - Senescence: Is It Universal or Not?
AB - Both demographic and physiological senescence have been demonstrated to occur in
various organisms. However, indeterminate growers, such as some animals and most
perennial plants, seem to escape the wear and tear of aging. Indeed, most
angiosperms show no signs of senescence, and both negligible and negative
senescence (improved physiological performance with aging) have been reported in
perennial plants growing in their natural habitat. In this opinion article, I
review recent developments in the study of senescence in perennial plants and
propose that continuous growth prevents senescence. I also address the question
whether senescence is a universal process.
PMID- 26442682
TI - Missing Pieces in the Puzzle of Plant MicroRNAs.
AB - Plant microRNAs (miRNAs) are important regulatory switches. Recent advances have
revealed many regulatory layers between the two essential processes, miRNA
biogenesis and function. However, how these multilayered regulatory processes
ultimately control miRNA gene regulation and connects miRNAs and plant responses
with the surrounding environment is still largely unknown. In this opinion
article, we propose that the miRNA pathway is highly dynamic and plastic. The
apparent flexibility of the miRNA pathway in plants appears to be controlled by a
number recently identified proteins and poorly characterized signaling cascades.
We further propose that altered miRNA accumulation can be a direct consequence of
the rewiring of interactions between proteins that function in the miRNA pathway,
an avenue that remains largely unexplored.
PMID- 26442683
TI - Genetic and Biochemical Mechanisms of Pollen Wall Development.
AB - The pollen wall is a specialized extracellular cell wall matrix that surrounds
male gametophytes and plays an essential role in plant reproduction. Uncovering
the mechanisms that control the synthesis and polymerization of the precursors of
pollen wall components has been a major research focus in plant biology. We
review current knowledge on the genetic and biochemical mechanisms underlying
pollen wall development in eudicot model Arabidopsis thaliana and monocot model
rice (Oryza sativa), focusing on the genes involved in the biosynthesis,
transport, and assembly of various precursors of pollen wall components. The
conserved and divergent aspects of the genes involved as well as their regulation
are addressed. Current challenges and future perspectives are also highlighted.
PMID- 26442684
TI - The introduction of early patient rehabilitation in surgery of soft tissue
sarcoma and its impact on post-operative outcome.
AB - BACKGROUND: Enhanced recovery after surgery (ERAS) programs are implemented in
multiple fields of surgery, but not yet in soft-tissue sarcoma (STS) surgery. We
wondered whether its introduction into STS surgery might have impacted
postoperative outcome. METHODS: Two hundred and fifty seven adult patients with
primary limb or trunk wall STS received ERAS from 2008 to 2012 as a part of the
intra-operative management. We evaluated, in retrospect, the intra-operative
management, post-operative outcomes, functional and oncological results of these
patients and compared them with 459 prior patients treated under a standard
recovery after surgery (SRAS) program from 1989 to 2007. RESULTS: The most
visible change from SRAS to ERAS in the perioperative management was decrease of
wound drainage (72% vs. 15%, p < 0.001) and increase of wound bandaging (16% vs.
66%; p < 0.001), underlining the appliance of the ERAS protocol. Post
operatively, hospital stay dropped from nine (0-74) to three (0-22) days (p <
0.001) without affecting major morbidity (8% vs. 5%, NS) or readmission to the
hospital (5% vs. 4%, NS). Functional outcome improved (p = 0.009) but whether
this change was due to ERAS remains to be proved because complementary treatments
changed over time. Tumour control remained unaffected, with an estimated risk of
local recurrence at 5 years of 12% in both groups. CONCLUSION: Introducing a
rapid recovery program was associated with a shorter hospitalization stay without
compromising surgical or oncological outcomes. The program appears to be safe and
reliable to use in patients undergoing STS surgery.
PMID- 26442685
TI - Drug adherence of patients with epilepsy in Iran: the effects of the
international economic sanctions.
AB - Drug adherence of patients with epilepsy was investigated to determine the
reasons behind poor adherence. In this retrospective chart review study, all
patients with a clinical diagnosis of epilepsy were recruited at the outpatient
epilepsy clinic at Shiraz University of Medical Sciences. We routinely asked
about the patient's drug adherence and reasons behind poor drug adherence in
every office visit. We defined drug adherence adequate if the patient reported
less than or equal to one missed dose per month. Patients' drug adherences were
investigated during two time periods: March 2010-2011 (before intensification of
the international economic sanctions against Iran), and September 2012-2013
(during intensified international economic sanctions). One hundred and ninety
nine patients were studied. Drug adherence was satisfactory in 139 patients (69.8
%) during the first time period. Drug adherence was satisfactory in 146 patients
(73.4 %) during the second time period. The most common reasons for poor drug
adherence was carelessness, followed by cost and lack of drug availability (1.5 %
in the first time period and 4 % in the second time period; P = 0.07). About one
third of patients with epilepsy had poor drug adherence. To overcome the problem,
it is important to find the reasons behind poor drug adherence in each patient
and try to overcome the cause. Purely from a clinical and patient care
perspective, it seems necessary that politicians should facilitate decisions that
make the health and well-being of ordinary people more affordable and without
hardship.
PMID- 26442686
TI - The influence of subthalamic nucleus stimulation on pragmatic language production
in Parkinson's disease.
AB - While the influence of deep brain stimulation (DBS) of the subthalamic nucleus
(STN) on the comprehension of pragmatic language in Parkinson's disease (PD) has
been the focus of studies, its impact on production, however, has yet to be
elucidated. (1) Investigating the inf luence of DBS STN on pragmatic language
production in spontaneous speech by comparing different stimulation conditions
and (2) evaluating the effect of asymmetric dopaminergic denervation. This paper
included 18 patients with advanced idiopathic PD with STN DBS. [Ten PD patients
with predominantly left hemispheric dopamine denervation (PD-left) and eight PD
patients with predominantly right-hemispheric dopamine denervation (PD-right).]
The pragmatic components 'communicative functions' and 'conversational skills'
were evaluated by analysing the spontaneous language production in four
stimulation conditions. STN stimulation did not appear to influence the pragmatic
production skills. Only when asymmetric dopamine depletion was taken into account
the parameter 'giving an explanation' interaction was detectable. STN DBS appears
to have some influence on the production of pragmatic language depending on
asymmetric dopaminergic denervation. Suggestions are made for further research of
pragmatic production in Parkinson's disease.
PMID- 26442687
TI - The determinants of depression in a Romanian cohort of multiple sclerosis
patients.
AB - The aim of the present study was to assess the prevalence of depression in a
large multiple sclerosis (MS) patient group and to analyse the physical and
psycho-socio-economic factors that influence its frequency and severity. In
total, 351 consecutive patients with a diagnosis of MS were included in this
study. All the patients completed a survey about their demographic
characteristics, marital status, presence of children, employment status,
educational level, duration of disease, disease course, duration of treatment and
type of disease modifying therapies (DMT). Their disability level was evaluated
using the Expanded Disability Status Scale (EDSS). Their depression level was
evaluated using the Romanian Version (2012) of the Beck Depression Inventory-II
(BDI-II). There was a significant positive correlation between the BDI-II score
and the actual age of the patients, their disease duration, EDSS and the number
of total relapses. From the EDSS functional scores, only the pyramidal score and
the sensitive score presented a significant association with BDI-II in the
logistic regression analysis. The BDI-II values decreased significantly with
increasing education level. In the case of the retired patients, the BDI-II
values were significantly higher. The BDI-II scores were also higher in widowers
and divorced patients and in patients with children. There was no significant
difference in the BDI-II values between different DMT groups. The main physical
and psycho-socio-economic determinants of depression in patients with MS are the
physical disability, disease duration, number of relapses, marital status,
education level, employment status, and the presence of children, but many
unsolved questions remain about the interrelations and relative contributions of
these factors, which necessitates further research. The DMTs did not
significantly influence the depression level.
PMID- 26442688
TI - Morphology of muscular function in chronic tension-type headache: a pilot study.
AB - Chronic pain has been thought to induce muscular changes in chronic tension-type
headache (CTTH) patients. As the knowledge of muscular responses in CTTH is
inconsistent, we decided to introduce new electromyogram signal shape
descriptors. We also wanted to compare the discriminatory power of proposed
indices with classical measures to establish their potential to act as markers
for CTTH. Thirty-eight headache patients with twenty healthy volunteers were
recruited. Twenty patients had CTTH, while 18 had migraine without aura. Surface
electromyogram data were recorded from right sternocleidomastoid and left
temporalis muscles during rest and in a headache-free situation. Besides
conventional root mean square (RMS) and median frequency (MDF), two morphological
based indices, skewness and kurtosis, were proposed to quantify the shape
variations of signal distribution. Results demonstrated that the skewness
outperformed RMS and MDF in terms of discriminatory power (p < 0.00). Kurtosis
values for both muscles differed considerably among study groups (p < 0.04). RMS
for both muscles was noticeably higher in CTTH group (p < 0.00). Regarding MDF,
migraineurs revealed highest (p < 0.05), while CTTH patients represented the
lowest values. Skewness was the most relevant predictor for headache diagnosis,
especially in temporalis muscle (migraine, odds ratio = 21.1, p = 0.01; Ctension
type headache, odds ratio = 78.8, p = 0.00). There are detectable distinct
muscular responses in chronic headache sufferers. This finding could be due to
adaptation to muscle underuse or sustained contraction, leading to impaired
recruitment and muscle fiber-type conversion with dominant type I fibers in CTTH.
PMID- 26442689
TI - Temporary conduction block in acute motor axonal neuropathy.
PMID- 26442690
TI - Is the chronic Tier-1 effect assessment approach for insecticides protective for
aquatic ecosystems?
AB - We investigated the appropriateness of several methods, including those
recommended in the Aquatic Guidance Document of the European Food Safety
Authority (EFSA), for the derivation of chronic Tier-1 regulatory acceptable
concentrations (RACs) for insecticides and aquatic organisms. The insecticides
represented different chemical classes (organophosphates, pyrethroids,
benzoylureas, insect growth regulators, biopesticides, carbamates,
neonicotinoids, and miscellaneous). Chronic Tier-1 RACs derived using toxicity
data for the standard species Daphnia magna, Chironomus spp., and/or Americamysis
bahia, were compared with Tier-3 RACs derived from micro- and mesocosm studies on
basis of the ecological threshold option (ETO-RACs). ETO-RACs could be derived
for 31 insecticides applied to micro- and mesocosms in single or multiple
applications, yielding a total number of 36 cases for comparison. The chronic
Tier-1 RACs calculated according to the EFSA approach resulted in a sufficient
protection level, except for 1 neonicotinoid (slightly underprotective) and for
several pyrethroids if toxicity data for A. bahia were not included. This latter
observation can be explained by 1) the fact that A. bahia is the most sensitive
standard test species for pyrethroids, 2) the hydrophobic properties of
pyrethroids, and 3) the fact that long-term effects observed in (epi) benthic
arthropods may be better explained by exposure via the sediment than via
overlying water. Besides including toxicity data for A. bahia, the protection
level for pyrethroids can be improved by selecting both D. magna and Chironomus
spp. as standard test species for chronic Tier-1 derivation. Although protective
in the majority of cases, the conservativeness of the recommended chronic Tier-1
RACs appears to be less than an order of magnitude for a relatively large
proportion of insecticides when compared with their Tier-3 ETO-RACs. This may
leave limited options for refinement of the chronic effect assessment using
laboratory toxicity data for additional species. Integr Environ Assess Manag
2016;12:747-758. (c) 2015 SETAC.
PMID- 26442691
TI - Trends form follows function: new ways to inform and inspire.
PMID- 26442692
TI - A learning experience.
PMID- 26442693
TI - System consolidation during sleep - a common principle underlying psychological
and immunological memory formation.
AB - Sleep benefits the consolidation of psychological memory, and there are hints
that sleep likewise supports immunological memory formation. Comparing
psychological and immunological domains, we make the case for active system
consolidation that is similarly established in both domains and partly conveyed
by the same sleep-associated processes. In the psychological domain, neuronal
reactivation of declarative memory during slow-wave sleep (SWS) promotes the
redistribution of representations initially stored in hippocampal circuitry to
extra-hippocampal circuitry for long-term storage. In the immunological domain,
SWS seems to favor the redistribution of antigenic memories initially held by
antigen-presenting cells, to persisting T cells serving as a long-term store.
Because storage capacities are limited in both systems, system consolidation
presumably reduces information by abstracting 'gist' for long-term storage.
PMID- 26442694
TI - The molecular constituents of the blood-brain barrier.
AB - The blood-brain barrier (BBB) maintains the optimal microenvironment in the
central nervous system (CNS) for proper brain function. The BBB comprises
specialized CNS endothelial cells with fundamental molecular properties essential
for the function and integrity of the BBB. The restrictive nature of the BBB
hinders the delivery of therapeutics for many neurological disorders. In
addition, recent evidence shows that BBB dysfunction can precede or hasten the
progression of several neurological diseases. Despite the physiological
significance of the BBB in health and disease, major discoveries of the molecular
regulators of BBB formation and function have occurred only recently. This review
highlights recent findings describing the molecular determinants and core
cellular pathways that confer BBB properties on CNS endothelial cells.
PMID- 26442695
TI - Priming the inflammatory pump of the CNS after traumatic brain injury.
AB - Traumatic brain injury (TBI) can lead to secondary neuropsychiatric problems that
develop and persist years after injury. Mounting evidence indicates that
neuroinflammatory processes progress after the initial head injury and worsen
with time. Microglia contribute to this inflammation by maintaining a primed
profile long after the acute effects of the injury have dissipated. This may set
the stage for glial dysfunction and hyperactivity to challenges including
subsequent head injury, stress, or induction of a peripheral immune response.
This review discusses the evidence that microglia become primed following TBI and
how this corresponds with vulnerability to a 'second hit' and subsequent
neuropsychiatric and neurodegenerative complications.
PMID- 26442697
TI - Depression as a microglial disease.
AB - Despite decades of intensive research, the biological mechanisms that causally
underlie depression are still unclear, and therefore the development of novel
effective antidepressant treatments is hindered. Recent studies indicate that
impairment of the normal structure and function of microglia, caused by either
intense inflammatory activation (e.g., following infections, trauma, stroke,
short-term stress, autoimmune or neurodegenerative diseases) or by decline and
senescence of these cells (e.g., during aging, Alzheimer's disease, or chronic
unpredictable stress exposure), can lead to depression and associated impairments
in neuroplasticity and neurogenesis. Accordingly, some forms of depression can be
considered as a microglial disease (microgliopathy), which should be treated by a
personalized medical approach using microglial inhibitors or stimulators
depending on the microglial status of the depressed patient.
PMID- 26442698
TI - Myeloid cells in Alzheimer's disease: culprits, victims or innocent bystanders?
AB - Several recent genome-wide association studies (GWAS) in patients with
neurodegenerative disorders have shed new light on the brain immune system,
suggesting that it plays a pivotal role in disease pathogenesis. Mononuclear
phagocytes are blatantly involved in Alzheimer's disease (AD) of the central
nervous system (CNS), but the specific functions of resident microglia,
perivascular or meningeal macrophages, and circulating myeloid cells have not yet
been fully resolved. Next-generation sequencing, high-throughput immune profiling
technologies, and novel genetic tools have recently revolutionized the
characterization of innate immune responses during AD. These studies advocate
selective and non-redundant roles for myeloid subsets, which could be a target
for novel disease-modifying therapies in AD.
PMID- 26442696
TI - Microglial malfunction: the third rail in the development of Alzheimer's disease.
AB - Studies of Alzheimer's disease (AD) have predominantly focused on two major
pathologies: amyloid-beta (Abeta) and hyperphosphorylated tau. These misfolded
proteins can accumulate asymptomatically in distinct regions over decades.
However, significant Abeta accumulation can be seen in individuals who do not
develop dementia, and tau pathology limited to the transentorhinal cortex, which
can appear early in adulthood, is usually clinically silent. Thus, an interaction
between these pathologies appears to be necessary to initiate and propel disease
forward to widespread circuits. Recent multidisciplinary findings strongly
suggest that the third factor required for disease progression is an aberrant
microglial immune response. This response may initially be beneficial; however, a
maladaptive microglial response eventually develops, fueling a feed-forward
spread of tau and Abeta pathology.
PMID- 26442699
TI - Systemic Juvenile Idiopathic Arthritis with Amyloidosis: An Uncommon Complication
with a Favourable Outcome.
PMID- 26442700
TI - Interprofessionalism between physicians and nurses: moving forward.
PMID- 26442701
TI - K11Cd2Sb5 built of an unprecedented planar CdSb3 triangle.
AB - The novel ternary Zintl phase K11Cd2Sb5 (1) with the unusual butterfly-shaped
[Cd2Sb5](11-) (1a) cluster anion has been prepared by employing an enhanced
stoichiometric proportion of K atoms that act as scissors. 1a is composed of two
corner-shared unprecedented planar CdSb3 triangles that represent the first
tricoordinated example of Cd unexpected for the octet rule.
PMID- 26442702
TI - Natural History and Implantable Cardioverter-Defibrillator Implantation After
Revascularization for Stable Coronary Artery Disease With Depressed Ejection
Fraction.
AB - BACKGROUND: Following revascularization, most payors require 3 months of medical
therapy, followed by left ventricular ejection fraction (LVEF) reassessment,
before implantable cardioverter-defibrillator (ICD) implantation possibly
contributing to incomplete follow-up and suboptimal utilization of ICD therapy.
The natural history of these patients, and their fate regarding ICD implantation,
is unknown. HYPOTHESIS: We hypothesized that a waiting period after
revascularization for stable CAD results in missed opportunities to provide care
with regard to ICD implantation. METHODS: We followed patients with LVEF <= 35%
and no ICD who underwent revascularization (coronary artery bypass grafting
[CABG] or percutaneous coronary intervention [PCI]) for stable CAD. Follow-up
used chart review and scripted telephone interviews. RESULTS: Among 3164
revascularized patients (2198 [69%] PCI, 966 [31%] CABG), only 62 (2%; 33 [53%]
male, age 67 +/- 12 y, LVEF 28% +/- 6%) had stable CAD, depressed LVEF, and no
ICD. Over 35 +/- 19 months, 35 (56%) of these 62 patients were no longer
candidates for ICD based on improved LVEF, 14 (23%) received an ICD, 5 (8%)
declined ICD despite physician recommendation, 3 (5%) were not offered ICD
despite continued eligibility, 2 (3%) died, 1 (2%) was not a candidate due to
substance abuse, and 1 (2%) had ICD implantation temporarily deferred. Only 1
(2%) was lost to follow-up. CONCLUSIONS: Following revascularization for stable
CAD with depressed LVEF, >=50% of patients' ventricular function improved enough
to make ICD implantation unnecessary. A waiting period after revascularization
prior to ICD implantation appears appropriate and does not significantly
negatively impact follow-up or the rate of appropriate ICD implantation.
PMID- 26442703
TI - R248Q mutation--Beyond p53-DNA binding.
AB - R248 in the DNA binding domain (DBD) of p53 interacts directly with the minor
groove of DNA. Earlier nuclear magnetic resonance (NMR) studies indicated that
the R248Q mutation resulted in conformation changes in parts of DBD far from the
mutation site. However, how information propagates from the mutation site to the
rest of the DBD is still not well understood. We performed a series of all-atom
molecular dynamics (MD) simulations to dissect sterics and charge effects of R248
on p53-DBD conformation: (i) wild-type p53 DBD; (ii) p53 DBD with an electrically
neutral arginine side-chain; (iii) p53 DBD with R248A; (iv) p53 DBD with R248W;
and (v) p53 DBD with R248Q. Our results agree well with experimental observations
of global conformational changes induced by the R248Q mutation. Our simulations
suggest that both charge- and sterics are important in the dynamics of the loop
(L3) where the mutation resides. We show that helix 2 (H2) dynamics is altered as
a result of a change in the hydrogen bonding partner of D281. In turn,
neighboring L1 dynamics is altered: in mutants, L1 predominantly adopts the
recessed conformation and is unable to interact with the major groove of DNA. We
focused our attention the R248Q mutant that is commonly found in a wide range of
cancer and observed changes at the zinc-binding pocket that might account for the
dominant negative effects of R248Q. Furthermore, in our simulations, the S6/S7
turn was more frequently solvent exposed in R248Q, suggesting that there is a
greater tendency of R248Q to partially unfold and possibly lead to an increased
aggregation propensity. Finally, based on the observations made in our
simulations, we propose strategies for the rescue of R248Q mutants.
PMID- 26442704
TI - Cardiac outflow morphogenesis depends on effects of retinoic acid signaling on
multiple cell lineages.
AB - BACKGROUND: Retinoic acid (RA), the bioactive derivative of vitamin A, is
essential for vertebrate heart development. Both excess and reduced RA signaling
lead to cardiovascular malformations affecting the outflow tract (OFT). To
address the cellular mechanisms underlying the effects of RA signaling during OFT
morphogenesis, we used transient maternal RA supplementation to rescue the early
lethality resulting from inactivation of the murine retinaldehyde dehydrogenase 2
(Raldh2) gene. RESULTS: By embryonic day 13.5, all rescued Raldh2(-/-) hearts
exhibit severe, reproducible OFT septation defects, although wild-type and
Raldh2(+/-) littermates have normal hearts. Cardiac neural crest cells (cNCC)
were present in OFT cushions of Raldh2(-/-) mutant embryos but ectopically
located in the periphery of the endocardial cushions, rather than immediately
underlying the endocardium. Excess mesenchyme was generated by Raldh2(-/-) mutant
endocardium, which displaced cNCC derivatives from their subendocardial, medial
position. CONCLUSIONS: RA signaling affects not only cNCC numbers but also their
position relative to endocardial mesenchyme during the septation process. Our
study shows that inappropriate coordination between the different cell types of
the OFT perturbs its morphogenesis and leads to a severe congenital heart defect,
persistent truncus arteriosus.
PMID- 26442705
TI - Epidemiological analysis of the distribution of cystic and alveolar
echinococcosis in Osh Oblast in the Kyrgyz Republic, 2000-2013.
AB - Alveolar and cystic echinococcosis are highly endemic in the Kyrgyz Republic.
This report documents the numbers of recorded cases of these two diseases that
have been reported in the past 14 years. The number of cases of echinococcosis
has increased from approximately 550 to 1044 cases in 2013. This is an increase
in incidence from 11.3 to 18.3 cases per 100,000 annually. In 2000 no cases of
alveolar echinococcosis (AE) were reported in the Kyrgyz Republic. During this
period the disease has emerged, with 148 cases reported in 2013 (2.6 cases per
100,000). Osh Oblast is a highly endemic focus for AE, with 60 cases reported in
2013 (6.0 per 100,000). The Alay Valley in the south of Osh Oblast reported the
majority of AE cases for this region. In this valley, in 2013, 42 cases of AE
were reported, which is a local incidence of 58 per 100,000.
PMID- 26442706
TI - Risk factors for Echinococcus coproantigen positivity in dogs from the Alay
valley, Kyrgyzstan.
AB - Echinococcosis, caused by the zoonotic cestodes Echinococcus granulosus (sensu
lato) and Echinococcus multilocularis, is highly endemic in the Central Asian
Republic of Kyrgyzstan, and is being identified increasingly as a public health
problem, especially amongst pastoral communities. As domestic dogs are considered
to be the main source of human infection, the identification of potential
transmission pathways is of relevance when considering implementing an
echinococcosis control scheme. The current report describes the results of an
analytical study of canine Echinococcus coproantigen enzyme-linked immunosorbent
assay (ELISA) prevalence in the Alay valley of southern Kyrgyzstan prior to the
commencement of regular praziquantel dosing of dogs. A logistic regression model
using a form of Bayes modal estimation was used to identify possible risk factors
for coproantigen positivity, and the output was interpreted in a Bayesian context
(posterior distributions of the coefficients of interest). The study found that
sheepdogs had lower odds of coproantigen positivity, as did dogs in households
with donkeys, where owners had knowledge of echinococcosis, and households which
engaged in home slaughtering. Surprisingly, there was no evidence of an
association between free roaming or previous praziquantel dosing and coproantigen
positivity, as has been found in previous studies. Possible reasons for these
findings are discussed in the context of the epidemiology of echinococcosis and
potential intervention approaches.
PMID- 26442707
TI - Canine echinococcosis: genetic diversity of Echinococcus granulosus sensu stricto
(s.s.) from definitive hosts.
AB - Canids, particularly dogs, constitute the major source of cystic echinococcosis
(CE) infection to humans, with the majority of cases being caused by Echinococcus
granulosus (G1 genotype). Canine echinococcosis is an asymptomatic disease caused
by adult tapeworms of E. granulosus sensu lato (s.l.). Information on the
population structure and genetic variation of adult E. granulosus is limited.
Using sequenced data of the mitochondrial cytochrome c oxidase subunit 1 (cox1)
we examined the genetic diversity and population structure of adult tapeworms of
E. granulosus (G1 genotype) from canid definitive hosts originating from various
geographical regions and compared it to that reported for the larval metacestode
stage from sheep and human hosts. Echinococcus granulosus (s.s) was identified
from adult tapeworm isolates from Kenya, Libya, Tunisia, Australia, China,
Kazakhstan, United Kingdom and Peru, including the first known molecular
confirmation from Gaza and the Falkland Islands. Haplotype analysis showed a star
shaped network with a centrally positioned common haplotype previously described
for the metacestode stage from sheep and humans, and the neutrality indices
indicated population expansion. Low Fst values suggested that populations of
adult E. granulosus were not genetically differentiated. Haplotype and nucleotide
diversities for E. granulosus isolates from sheep and human origin were twice as
high as those reported from canid hosts. This may be related to self
fertilization of E. granulosus and/or to the longevity of the parasite in the
respective intermediate and definitive hosts. Improved nuclear single loci are
required to investigate the discrepancies in genetic variation seen in this
study.
PMID- 26442708
TI - The development of Angiostrongylus vasorum (Baillet, 1866) in the freshwater
snail Pomacea canaliculata (Lamarck, 1822).
AB - Angiostrongylus vasorum is a parasitic nematode that infects the heart and
pulmonary artery and its branches of domestic and wild canids. The parasite can
use several species of terrestrial and aquatic molluscs as intermediate hosts,
although susceptibility varies. Pomacea canaliculata is a mollusc found in lakes,
swamps and rivers in South America. In this study, we evaluated the
susceptibility, parasite growth, oviposition and larval development of 282 P.
canaliculata infected with 500 A. vasorum first-instar larvae (L1). From day 5
post-infection (pi) to day 30 pi, seven specimens per day were sacrificed to
recover the larval instars. We compared 50 egg masses from infected and
uninfected molluscs to determine the number of eggs per clutch, the hatching rate
and the growth of the molluscs. The percentage of recovered larvae ranged from
39.17% to 67.5%. First-stage larvae (L1) were found until day 19 pi, second-stage
larvae (L2) were found from days 11 to 25 pi, and third-stage larvae (L3) were
recovered only after day 19 pi. Infected snails exhibited the most eggs during
spawning, although the rate of hatching and shell size were lower in the infected
snails compared with controls. This is the first report of an experimental
infection of P. canaliculata with A. vasorum, and the results confirm the non
specificity of the nematode in relation to the intermediate host and indicate the
importance of epidemiological surveys of this parasite and mollusc.
PMID- 26442709
TI - Regioselective synthesis of 2H-indazoles through Ga/Al- and Al-mediated direct
alkylation reactions of indazoles.
AB - A procedure has been developed for the regioselective, high yielding synthesis of
2H-indazoles that involves direct alkylation of indazoles with various allyl and
benzyl bromides, and alpha-bromocarbonyl compounds.
PMID- 26442710
TI - Is It Migralepsy? Still Don't Know.
PMID- 26442711
TI - Helicobacter pylori virulence genes in the five largest islands of Indonesia.
AB - BACKGROUND: It remains unclear whether the low incidence of gastric cancer in
Indonesia is due to low infection rates only or is also related to low
Helicobacter pylori pathogenicity. We collected H. pylori strains from the five
largest islands in Indonesia and evaluated genetic virulence factors. METHODS:
The genotypes of H. pylori virulence factors were determined by polymerase chain
reaction (PCR)-based sequencing. Histological severity of the gastric mucosa was
classified into 4 grades, according to the updated Sydney system. RESULTS: A
total of 44 strains were analyzed. Forty-three (97.7 %) were cagA-positive: 26
(60.5 %) were East-Asian-type-cagA, 9 (20.9 %) were Western-type-cagA, and 8
(18.6 %) were novel ABB-type, most of which were obtained from Papuan. EPIYT
sequences were more prevalent than EPIYA sequences (P = 0.01) in the EPIYA-B
motif of all types of cagA. The majority of cagA-positive strains (48.8 %, 21/43)
had a 6-bp deletion in the first pre-EPIYA region. Subjects infected with East
Asian-type-cagA strains with a 6-bp deletion had significantly lower inflammation
and atrophy scores in the corpus than those infected with Western-type-cagA
strains (both P = 0.02). In total, 70.4 % of strains possessed the vacA s1m1
genotype and 29.5 % were m2. All strains from peptic ulcer patients were of the
iceA1 genotype, which occurred at a significantly higher proportion in peptic
ulcer patients than that in gastritis patients (55.3 %, P = 0.04). The double
positive genotype of jhp0562/beta-(1,3)galT was predominant (28/44, 63.6 %), and
subjects infected with this type had significantly higher inflammation scores in
the corpus than those with the jhp0562 negative/beta-(1,3)galT positive genotype
(mean [median]; 1.43 [1] vs. 0.83 [1], P = 0.04). There were significant
differences in cagA and pre-EPIYA cagA type, oipA status, and jhp0562/beta
(1,3)galT type among different ethnic groups (P < 0.05). CONCLUSIONS: In addition
to a low H. pylori infection rate, the low incidence of gastric cancer in
Indonesia might be attributed to less virulent genotypes in predominant strains,
which are characterized by the East-Asian-type-cagA with a 6-bp deletion and
EPIYT motif, a high proportion of m2, dupA negative or short type dupA, and the
jhp0562/beta-(1,3)galT double positive genotype.
PMID- 26442713
TI - Fabrication of Thermoresponsive Nanoactinia Tentacles by a Single Particle
Nanofabrication Technique.
AB - Nanowires that are retractable by external stimulus are the key to fabrication of
nanomachines that mimick actinia tentacles in nature. A single particle
nanofabrication technique (SPNT) was applied over a large area to the fabrication
of retractable nanowires (nanoactinia tentacles) composed of poly(N
isopropylacrylamide) (PNIPAM) and poly(vinylpyrrolidone) (PVP), which are
thermoresponsive and hydrophilic polymers. The nanowires were transformed with
increasing temperature from rod-like- to globule-forms with gyration radii of
~1.5 and ~0.7 MUm, respectively. The transformation of the nanowires was
reversible and reproducible under repeated cycles of heating and cooling. The
reversible transformation was driven by hydration and dehydration of PNIPAM, the
thermoresponsive segments, resulting in coil-to-globule transformation of the
segments. The nanoactinia tentacle systems trapped the nanoparticles as a model
of living cells under thermal stimulation, and the trapping was controlled by
temperature. We present herein a unique nanomachine system which can be
applicable to nanoparticle filtering/sensing systems and expandable to large-area
functionalization and demonstrate polymer-based nanoactuators via scaling of
molecular level coil-to-globule transformation into micron-sizes.
PMID- 26442712
TI - Maximizing oyster-reef growth supports green infrastructure with accelerating sea
level rise.
AB - Within intertidal communities, aerial exposure (emergence during the tidal cycle)
generates strong vertical zonation patterns with distinct growth boundaries
regulated by physiological and external stressors. Forecasted accelerations in
sea-level rise (SLR) will shift the position of these critical boundaries in ways
we cannot yet fully predict, but landward migration will be impaired by coastal
development, amplifying the importance of foundation species' ability to maintain
their position relative to rising sea levels via vertical growth. Here we show
the effects of emergence on vertical oyster-reef growth by determining the
conditions at which intertidal reefs thrive and the sharp boundaries where reefs
fail, which shift with changes in sea level. We found that oyster reef growth is
unimodal relative to emergence, with greatest growth rates occurring between 20
40% exposure, and zero-growth boundaries at 10% and 55% exposures. Notably, along
the lower growth boundary (10%), increased rates of SLR would outpace reef
accretion, thereby reducing the depth range of substrate suitable for reef
maintenance and formation, and exacerbating habitat loss along developed
shorelines. Our results identify where, within intertidal areas, constructed or
natural oyster reefs will persist and function best as green infrastructure to
enhance coastal resiliency under conditions of accelerating SLR.
PMID- 26442714
TI - Separation and characterization of polyphenolics from underutilized byproducts of
fruit production (Choerospondias axillaris peels): inhibitory activity of
proanthocyanidins against glycolysis enzymes.
AB - Bioactive proanthocyanidins were isolated from the peel of Choerospondias
axillaris fruit, which is a waste product of the food processing industry.
Compositional analysis indicated that the proanthocyanidins had extension units
mainly consisting of epicatechin gallate or epicatechin, and terminal units
mainly consisting of catechin. Numerous polymeric forms of the molecules were
detected, including monomers, dimers, and trimers. Certain fractions exhibited
strong alpha-amylase or alpha-glucosidase inhibition in a dose-dependent manner.
Furthermore, their inhibitory activities depended on their degree of
polymerization and galloylation. For example, the most bioactive fraction had
alpha-amylase and alpha-glucosidase inhibitory activities (IC50 values) of 541
and 3.1 MUg mL(-1), respectively. This study demonstrates that proanthocyanidins
from C. axillaris peels can inhibit carbohydrate digestive enzymes in vitro and
may therefore serve as antidiabetic ingredients in functional or medical foods.
PMID- 26442715
TI - Dental students' perceptions of undergraduate clinical training in oral and
maxillofacial surgery in an integrated curriculum in Saudi Arabia.
AB - PURPOSE: The aim was to understand dental students' experiences with oral and
maxillofacial surgery (OMS) teaching, their confidence levels in performing
routine dento-alveolar operations, and the relationship between the students'
confidence level and the number of teeth extracted during the clinical practice.
METHODS: The survey questionnaire was distributed to 32 students at Aljouf
University College of Dentistry, Saudi Arabia during their fourth and fifth year
in 2015. Respondents were asked to rate 19 items, which represent a student's
confidence in performing routine surgical interventions, using a four-point
Likert scale (1=very little confidence, 4=very confident). A multivariate
regression was computed between average confidence and the variables: weekly
hours devoted to studying oral and maxillofacial surgery, college grade point
average, and the total number of teeth extracted. RESULTS: The response rate was
100%. Students revealed the highest level of confidence in giving local
anesthesia (96.9%), understanding extraction indications (93.8%), and performing
simple extractions (90.6%). Less confidence was shown with handling difficult
extractions (50.0%), extracting molars with separation (50.0%) or extracting
third molars (56.3%). The average confidence in performing surgical procedures
was 2.88 (SD=0.55), ranging from 1.79 to 3.89. A given student's confidence
increased with an increase in the total number of teeth extracted (P=0.003).
CONCLUSION: It reveals a significant impact of undergraduate clinical training on
students' confidence in performing oral and maxillofacial surgery clinical
procedures: The more clinical experience the students had, the more confidence
they reported.
PMID- 26442716
TI - Analysis of the study skills of undergraduate pharmacy students of the University
of Zambia School of Medicine.
AB - It aimed to compare the study skills of two groups of undergraduate pharmacy
students in the School of Medicine, University of Zambia using the Study Skills
Assessment Questionnaire (SSAQ), with the goal of analysing students' study
skills and identifying factors that affect study skills. A questionnaire was
distributed to 67 participants from both programs using stratified random
sampling. Completed questionnaires were rated according to participants study
skill. The total scores and scores within subscales were analysed and compared
quantitatively. Questionnaires were distributed to 37 students in the regular
program, and to 30 students in the parallel program. The response rate was 100%.
Students had moderate to good study skills: 22 respondents (32.8%) showed good
study skills, while 45 respondents (67.2%) were found to have moderate study
skills. Students in the parallel program demonstrated significantly better study
skills (mean SSAQ score, 185.4+/-14.5), particularly in time management and
writing, than the students in the regular program (mean SSAQ score 175+/-25.4;
P<0.05). No significant differences were found according to age, gender,
residential or marital status, or level of study. The students in the parallel
program had better time management and writing skills, probably due to their
prior work experience. The more intensive training to students in regular program
is needed in improving time management and writing skills.
PMID- 26442717
TI - Clinical significance of stem cell marker CD133 expression in colorectal cancer.
AB - OBJECTIVE: CD133, a glycoprotein, is expressed in different types of human stem
cells and tumor cells. Detection of altered CD133 expression in colorectal cancer
tissues could be useful as a marker for the prediction of colorectal
tumorigenesis, progression, and prognosis. METHODS: A total of 19 fresh and 145
paraffin-embedded tissue specimens from colorectal cancer patients were obtained
for detection of CD133 expression using flow cytometry and immunohistochemistry,
respectively. The tumorigenic capacity of tumor cells from 19 patients was
assessed in nude mice. Association of CD133 expression was then analyzed for
clinical significance. RESULTS: The percentage of CD133-positive (CD133+) tumor
cell population ranged between 0.84% and16.75% (mean ratio =7.15%) of tumor cells
in the 19 freshly isolated tissue samples. CD133 expression in tumor cells was
associated with tumor lymph node metastasis (9.81% vs. 3.22%; p=0.013) and poor
tumor differentiation (8.32% vs. 5.07%; p=0.043). In the 145 paraffin-embedded
samples, CD133+ colorectal cancer was also associated with local recurrence of
tumorigenesis (p=0.035) and distant metastasis (p=0.017), while patients with
over 5% CD133+ tumor cells exhibited a decreased survival rate (p=0.001).
Multivariate COX analysis showed that the depth of tumor invasion, histology,
stagWaes, lymph node metastasis, and CD133 expression were all independent
prognosis factors for colorectal cancer (p=0.032, 0.011, 0.001, 0.002, and 0.030,
respectively). Furthermore, as few as 5,000 CD133+ colorectal cancer HCT116 cells
were sufficient to form tumor xenografts, whereas 1x105 CD133- tumor cells failed
to develop tumor xenografts in nude mice. CONCLUSIONS: CD133 expression is a
useful biomarker for prediction of colorectal cancer progression and survival of
patients.
PMID- 26442719
TI - Anthropogenic phosphorus flows under different scenarios for the city of
Stockholm, Sweden.
AB - Today, concerns prevail about the unsustainable use of phosphorus and worldwide
eutrophication, thus requiring efficient management of phosphorus flows. With
increasing population and associated urban growth, urban management of phosphorus
flows in the perspectives of recycling, eutrophication and total budget becomes
increasingly important. This study mapped phosphorus flows for a reference year
(2013) and a future year (2030) using different scenarios for the city of
Stockholm, Sweden. The results indicated that the Swedish goal of recycling
phosphorus from wastewater would cover the majority of the total phosphorus
budget for Stockholm. However, in 2013, only 10% of phosphorus was recycled for
agricultural use, around half of which was from sewage sludge and the other half
from food waste. Almost 50% of total phosphorus was sent to landfill/mining waste
capping with sewage sludge, for economic reasons and lack of market. Among the
scenarios of upstream and downstream urban management options studied in
combination with population growth, recovery of phosphorus from sewage sludge had
the greatest potential to increase the fraction recycled to agriculture. However,
only upstream measures, e.g. changed diet, were able to reduce the total
phosphorus budget. Urban management of phosphorus flows based on the different
perspectives of recycling, eutrophication or total budget was shown to
potentially result in different preferred management actions and both upstream
and downstream measures need to be considered. Moreover, management needs to pay
attention to small but environmentally sensitive flows, particularly when setting
city goals on phosphorus recycling by percentage in a large budget.
PMID- 26442718
TI - Linking pattern recognition and salicylic acid responses in Arabidopsis through
ACCELERATED CELL DEATH6 and receptors.
AB - The Arabidopsis membrane protein ACCELERATED CELL DEATH 6 (ACD6) and the defense
signal salicylic acid (SA) are part of a positive feedback loop that regulates
the levels of at least 2 pathogen-associated molecular patterns (PAMP) receptors,
including FLAGELLIN SENSING 2 (FLS2) and CHITIN ELICITOR RECEPTOR (LYSM domain
receptor-like kinase 1, CERK1). ACD6- and SA-mediated regulation of these
receptors results in potentiation of responses to FLS2 and CERK1 ligands (e.g.
flg22 and chitin, respectively). ACD6, FLS2 and CERK1 are also important for
callose induction in response to an SA agonist even in the absence of PAMPs.
Here, we report that another receptor, EF-Tu RECEPTOR (EFR) is also part of the
ACD6/SA signaling network, similar to FLS2 and CERK1.
PMID- 26442720
TI - Controlling phosphate releasing from poultry litter using stabilized Fe-Mn binary
oxide nanoparticles.
AB - Animal wastes contain high concentrations of phosphorus (P), most of which is
lost into the environment due to uncontrolled release rates. Polysaccharide
stabilized Fe-Mn binary oxide nanoparticles were prepared and tested for
phosphate adsorption from water and for controlling leachability of P from
poultry litter. A water soluble starch and carboxymethyl cellulose (CMC) were
used as a stabilizer. Both the Freundlich and Langmuir models were able to
adequately interpret the isotherm data. The Langmuir maximum capacity was
determined at 252, 298 and 313 mg-P/g for bare, CMC- and starch-stabilized
nanoparticles, respectively. The presence of the stabilizers not only enhanced
the sorption capacity, but facilitated delivery and dispersion of the
nanoparticles in poultry litter (PL) and in soil. High phosphate sorption
capacity was observed over a broad pH range of 4-9. FTIR analyses indicated that
inner sphere surface complexation (Fe-O-P) was the key mechanism for the enhanced
uptake of P. When applied to poultry litter, the stabilized nanoparticles reduced
water leachable phosphate by >86% at a dose of 0.2 g/L as Fe, and simultaneously,
water leachable arsenic by >87-95%. Under conditions of simulated land
application of PL, the nanoparticle amendment of PL reduced the water soluble P
from 66% (for untreated PL) to 4.4%, and lowered the peak soluble P concentration
from 300 to <20 mg/L. By transferring the peak soluble P to the nanoparticle
bound P, the nanoparticles not only greatly reduce the potential runoff loss of P
from PL, but also provide a long-term slow-releasing nutrient source.
Fortuitously, the nanoparticle treatment was able to immobilize arsenic from PL.
With excellent adsorption capacity, easy deliverability, low cost and
environmental innocuousness, the stabilized Fe-Mn nanoparticles appear promising
for controlling P releases from poultry litter or other animal wastes and for
phosphate recovery from water.
PMID- 26442721
TI - Time to help.
PMID- 26442722
TI - [Norway on the overdose top?].
PMID- 26442723
TI - [Re: All suicides are not due to treatment failure].
PMID- 26442724
TI - [Re: The emergency department needs their own specialists].
PMID- 26442726
TI - [Chronic lymphatic leukemia in Norway-incidence and prognosis at diagnosis time].
PMID- 26442727
TI - [Familial occurrence of chronic lymphatic leukemia in Norway].
PMID- 26442728
TI - [Emergency prevention in overweight--to be trusted?].
PMID- 26442730
TI - [In Process Citation].
PMID- 26442729
TI - [Where is the boundary between diagnostics and research?].
PMID- 26442731
TI - [In Process Citation].
PMID- 26442732
TI - Prevalence and incidence of epilepsy in the Nordic countries.
AB - BACKGROUND: Updated knowledge on the prevalence of epilepsy is valuable for
planning of health services to this large and complex patient group.
Comprehensive epidemiological research on epilepsy has been undertaken, but
because of variations in methodology, the results are difficult to compare. The
objective of this article is to present evidence-based estimates of the
prevalence and incidence of epilepsy in the Nordic countries. METHOD: The article
is based on a search in PubMed with the search terms epilepsy and epidemiology,
combined with each of the Nordic countries separately. RESULTS: Altogether 38
original articles reported incidence and/or prevalence rates of epilepsy in a
Nordic country. Four studies had investigated the prevalence of active epilepsy
in all age groups, with results ranging from 3.4 to 7.6 per 1,000 inhabitants.
Only two studies had investigated the incidence of epilepsy in a prospective
material that included all age groups. The reported incidence amounted to 33 and
34 per 100,000 person-years respectively. A prospective study that only included
adults reported an incidence of 56 per 100,000 person-years. INTERPRETATION: We
estimate that approximately 0.6% of the population of the Nordic countries have
active epilepsy, i.e. approximately 30,000 persons in Norway. Epilepsy is thus
one of the most common neurological disorders. The incidence data are more
uncertain, but we may reasonably assume that 30-60 new cases occur per 100,000
person-years.
PMID- 26442733
TI - Neuroprotective effects of hypothermia.
AB - BACKGROUND: The neuroprotective effects of hypothermia have been shown in case
reports and animal studies. Therapeutic hypothermia is used to provide
neuroprotection during certain types of surgery and after serious events that
pose a threat to the brain. The aim of this review is to describe the efficacy of
such treatment in adults. METHOD: All articles retrieved from five searches in
PubMed were examined. Studies were included if they had a hypothermia protocol
and a measurement of neuroprotection. The list of randomised studies was
completed using studies identified from five international review articles. In
all, 103 of 678 studies fulfilled the inclusion criteria, of which 48 were
clinical trials. Ten of the clinical trials were randomised, using a normothermic
control group. RESULTS: Several randomised clinical trials have suggested that
avoidance of hyperthermia provides the same neuroprotection as therapeutic
hypothermia after cardiac arrest and traumatic brain injury, but prognostic
factors and inclusion criteria vary markedly between the patient populations,
including time to target temperature. Two studies found that cognitive function
after prolonged aortic surgery under deep hypothermia was equivalent to that
after brief normothermic interventions. Animal studies show a neuroprotective
effect of hypothermia, but this is dependent on the extent of anoxic damage as
well as the rate of cooling. INTERPRETATION: It remains uncertain how best to
implement therapeutic hypothermia to achieve neuroprotection after acute events
that pose a threat to the brain. Hypothermia during aortic surgery seems to
provide adequate neuroprotection for prolonged interventions.
PMID- 26442734
TI - [An itchy souvenir].
PMID- 26442735
TI - [A woman with pareses of the arms and legs].
AB - BACKGROUND: Hypokalemic pareses are caused by low extracellular potassium levels
which reduce the resting membrane potential of muscle cells and make them less
excitable. It may be caused by an intracellular shift of potassium, renal
potassium loss, reduced potassium intake or increased gastrointestinal loss. CASE
PRESENTATION: A woman in her 60s presented with rapid-onset tetraparesis and
hyporeflexia starting the day before admission. The patient history revealed
several months of low food intake, increased alcohol consumption and diarrhoea.
Laboratory tests showed severe hypokalemia (1.5 mmol/l) and hypomagnesemia (0.38
mmol/l), and ECG showed atrial fibrillation. She was admitted to the medical
intensive care unit and treated with intravenous normal saline with added
potassium and magnesium, with good effect on her symptoms. Urine tests showed
high potassium-creatinine ratio (4.22 mmol/mmol creatinine) and increased
fractional excretion of magnesium (18.6%). Abdominal CT scan revealed colonic
wall thickening, and colonic biopsies showed mild inflammation. Faecal
calprotectin was moderately elevated (294 mg/kg). INTERPRETATION: The patient had
hypokalemic pareses for which there were several contributing factors. The renal
causes were augmented excretion of magnesium and potassium, probably due to
increased alcohol consumption. The extrarenal causes were increased
gastrointestinal loss, with ulcerative colitis being the presumed explanation,
and reduced food intake.
PMID- 26442736
TI - [Nanomedicine in cancer treatment--small particles brings hope].
PMID- 26442737
TI - International collaboration in postgraduate training.
PMID- 26442738
TI - [Discontinuation].
PMID- 26442740
TI - [In Process Citation].
PMID- 26442739
TI - [E. Hem replies].
PMID- 26442742
TI - [Choice of specialty--a choice for life].
PMID- 26442743
TI - [The highest priority].
PMID- 26442749
TI - A simple practical balloon anchoring technique within the guide catheter for
chronic total occlusion (CTO) of the coronary artery.
PMID- 26442748
TI - DTI and VBM reveal white matter changes without associated gray matter changes in
patients with idiopathic restless legs syndrome.
AB - BACKGROUND AND PURPOSE: We evaluated cerebral white and gray matter changes in
patients with iRLS in order to shed light on the pathophysiology of this disease.
METHODS: Twelve patients with iRLS were compared to 12 age- and sex-matched
controls using whole-head diffusion tensor imaging (DTI) and voxel-based
morphometry (VBM) techniques. Evaluation of the DTI scans included the voxelwise
analysis of the fractional anisotropy (FA), radial diffusivity (RD), and axial
diffusivity (AD). RESULTS: Diffusion tensor imaging revealed areas of altered FA
in subcortical white matter bilaterally, mainly in temporal regions as well as in
the right internal capsule, the pons, and the right cerebellum. These changes
overlapped with changes in RD. Voxel-based morphometry did not reveal any gray
matter alterations. CONCLUSIONS: We showed altered diffusion properties in
several white matter regions in patients with iRLS. White matter changes could
mainly be attributed to changes in RD, a parameter thought to reflect altered
myelination. Areas with altered white matter microstructure included areas in the
internal capsule which include the corticospinal tract to the lower limbs,
thereby supporting studies that suggest changes in sensorimotor pathways
associated with RLS.
PMID- 26442750
TI - Assessment of Different Quit Smoking Methods Selected by Patients in Tobacco
Cessation Centers in Iran.
AB - BACKGROUND: Health systems play key roles in identifying tobacco users and
providing evidence-based care to help them quit. This treatment includes
different methods such as simple medical consultation, medication, and telephone
counseling. To assess different quit smoking methods selected by patients in
tobacco cessation centers in Iran in order to identify those that are most
appropriate for the country health system. METHODS: In this cross-sectional and
descriptive study, a random sample of all quit centers at the country level was
used to obtain a representative sample. Patients completed the self-administered
questionnaire which contained 10 questions regarding the quality, cost, effect,
side effects and the results of quitting methods using a 5-point Likert-type
scale. Percentages, frequencies, mean, T-test, and variance analyses were
computed for all study variables. RESULTS: A total of 1063 smokers returned
completed survey questionnaires. The most frequently used methods were Nicotine
Replacement Therapy (NRT) and combination therapy (NRT and Counseling) with 228
and 163 individuals reporting these respectively. The least used methods were
hypnotism (n = 8) and the quit and win (n = 17). The methods which gained the
maximum scores were respectively the combined method, personal and Champix with
means of 21.4, 20.4 and 18.4. The minimum scores were for e-cigarettes, hypnotism
and education with means of 12.8, 11 and 10.8, respectively. There were
significant differences in mean scores based on different cities and different
methods. CONCLUSIONS: According to smokers' selection the combined therapy,
personal methods and Champix are the most effective methods for quit smoking and
these methods could be much more considered in the country health system.
PMID- 26442752
TI - Lower platelet counts and antiplatelet therapy independently predict better
outcomes in patients with head and neck squamous cell carcinoma: a retrospective
analysis.
AB - The paper by Rachidi et al. suggests that antiplatelet drugs may play a role in
ameliorating the clinical outcome in a large series of patients with head and
neck cancer managed with either surgery or radiation. Our data, as well as
confirming the results observed by the authors, enhance their clinical relevance
pointing out the effect of antiplatelet drugs in terms of locoregional control in
the setting of patients with advanced head and neck cancer managed with
definitive chemo-radiotherapy.
PMID- 26442753
TI - The inhibitory effect of Thymus vulgaris extracts on the planktonic form and
biofilm structures of six human pathogenic bacteria.
AB - OBJECTIVE: Microorganisms are responsible for many problems in industry and
medicine because of biofilm formation. Therefore, this study was aimed to examine
the effect of Thymus vulgaris (T. vulgaris) extracts on the planktonic form and
biofilm structures of six pathogenic bacteria. MATERIALS AND METHODS:
Antimicrobial activities of the plant extracts against the planktonic form of the
bacteria were determined using the disc diffusion method. MIC and MBC values were
evaluated using macrobroth dilution technique. Anti-biofilm effects were assessed
by microtiter plate method. RESULTS: According to disc diffusion test (MIC and
MBC), the ability of Thymus vulgaris (T. vulgaris ) extracts for inhibition of
bacteria in planktonic form was confirmed. In dealing with biofilm structures,
the inhibitory effect of the extracts was directly correlated to their
concentration. Except for the inhibition of biofilm formation, efficacy of each
extract was independent from type of solvent. CONCLUSION: According to the
potential of Thymus vulgaris (T. vulgaris) extracts to inhibit the test bacteria
in planktonic and biofilm form, it can be suggested that Thymus vulgaris (T.
vulgaris) extracts can be applied as antimicrobial agents against the pathogenic
bacteria particularly in biofilm forms.
PMID- 26442751
TI - Neural basis of motivational approach and withdrawal behaviors in
neurodegenerative disease.
AB - INTRODUCTION: The Behavioral Inhibition System (BIS) and the Behavioral
Activation System (BAS) have been theorized as neural systems that regulate
approach/withdrawal behaviors. Behavioral activation/inhibition balance may
change in neurodegenerative disease based on underlying alterations in systems
supporting motivation and approach/withdrawal behaviors, which may in turn be
reflected in neuropsychiatric symptoms. METHOD: A total of 187 participants (31
patients diagnosed with behavioral variant of FTD [bvFTD], 13 semantic variant of
primary progressive aphasia [svPPA], 14 right temporal variant FTD [rtFTD], 54
Alzheimer's disease [AD], and 75 older healthy controls [NCs]) were included in
this study. Changes in behavioral inhibition/activation were measured using the
BIS/BAS scale. We analyzed the correlation between regional atrophy pattern and
BIS/BAS score, using voxel-based morphometry (VBM). RESULTS: ADs had
significantly higher BIS scores than bvFTDs and NCs. bvFTDs activation-reward
response (BAS-RR) was significantly lower than ADs and NCs, though their
activation-drive (BAS-D) was significantly higher than in ADs. Both AD and rtFTD
patients had abnormally low activation fun-seeking (BAS-FS) scores. BIS score
correlated positively with right anterior cingulate and middle frontal gyrus
volume, as well as volume in the right precentral gyrus and left
insula/operculum. CONCLUSIONS: AD, bvFTD, and rtFTD patients show divergent
patterns of change in approach/withdrawal reactivity. High BIS scores correlated
with preservation of right-predominant structures involved in task control and
self-protective avoidance of potentially negative reinforcers. Damage to these
regions in bvFTD may create a punishment insensitivity that underlies patients'
lack of self-consciousness in social contexts.
PMID- 26442754
TI - Preventive brain radio-chemotherapy alters plasticity associated metabolite
profile in the hippocampus but seems to not affect spatial memory in young
leukemia patients.
AB - BACKGROUND: Neuronal plasticity leading to evolving reorganization of the
neuronal network during entire lifespan plays an important role for brain
function especially memory performance. Adult neurogenesis occurring in the
dentate gyrus of the hippocampus represents the maximal way of network
reorganization. Brain radio-chemotherapy strongly inhibits adult hippocampal
neurogenesis in mice leading to impaired spatial memory. METHODS: To elucidate
the effects of CNS radio-chemotherapy on hippocampal plasticity and function in
humans, we performed a longitudinal pilot study using 3T proton magnetic
resonance spectroscopy ((1)H-MRS) and virtual water-maze-tests in 10 de-novo
patients with acute lymphoblastic leukemia undergoing preventive whole brain
radio-chemotherapy. Patients were examined before, during and after treatment.
RESULTS: CNS radio-chemotherapy did neither affect recall performance in probe
trails nor flexible (reversal) relearning of a new target position over a time
frame of 10 weeks measured by longitudinal virtual water-maze-testing, but
provoked hippocampus-specific decrease in choline as a metabolite associated with
cellular plasticity in (1)H-MRS. CONCLUSION: Albeit this pilot study needs to be
followed up to definitely resolve the question about the functional role of adult
human neurogenesis, the presented data suggest that (1)H-MRS allows the detection
of neurogenesis-associated plasticity in the human brain.
PMID- 26442755
TI - Copy number loss upstream of RAI1 uncovers gene expression regulatory region that
may impact Potocki-Lupski syndrome diagnosis.
AB - The identification of structural variants of uncertain clinical significance is
increasing; however, studies delineating the functional consequence of these
variants in the pathogenicity of phenotypic features are lacking. Understanding
the consequence of structural variants such as copy number alterations and their
role in gene expression changes is paramount in order to perform a comprehensive
analysis of genetic effects on phenotypic variation and disease. RAI1 is a dosage
sensitive essential neurodevelopmental gene. Copy number loss of RAI1 results in
Smith-Magenis syndrome while copy number gain results in Potocki-Lupski syndrome.
Here, we present a case of a six year old female with a newly identified
maternally inherited copy number loss that lies within the Smith-Magenis syndrome
common deletion region, but RAI1 copy number is normal. Integration of the
Encyclopedia of DNA Elements (ENCODE) data at the affected region suggests that
the deletion disrupts several cis-acting regulatory elements upstream of RAI1,
such as multiple repressor sites and an insulator region. Gene expression studies
revealed that both the proband and the mother have significantly elevated RAI1
mRNA levels suggesting that the structural variant alters gene expression
regulation. The proband and the mother both have some features of Potocki-Lupski
syndrome, while the child appears to be more affected with autistic-like
features. Overall, our work demonstrates that the integration of ENCODE data with
structural variants of uncertain significance aids in delineating a functional
consequence to a genomic aberration and subsequent diagnosis.
PMID- 26442756
TI - An integrative Raman microscopy-based workflow for rapid in situ analysis of
microalgal lipid bodies.
AB - BACKGROUND: Oils and bioproducts extracted from cultivated algae can be used as
sustainable feedstock for fuels, nutritional supplements, and other bio-based
products. Discovery and isolation of new algal species and their subsequent
optimization are needed to achieve economical feasibility for industrial
applications. Here we describe and validate a workflow for in situ analysis of
algal lipids through confocal Raman microscopy. We demonstrate its effectiveness
to characterize lipid content of algal strains isolated from the environment as
well as algal cells screened for increased lipid accumulation through UV
mutagenesis combined with Fluorescence Activated Cell Sorting (FACS). RESULTS: To
establish and validate our workflow, we refined an existing Raman platform to
obtain better discrimination in chain length and saturation of lipids through
ratiometric analyses of mixed fatty acid lipid standards. Raman experiments were
performed using two different excitation lasers (lambda = 532 and 785 nm), with
close agreement observed between values obtained using each laser. Liquid
chromatography coupled with mass spectrometry (LC-MS) experiments validated the
obtained Raman spectroscopic results. To demonstrate the utility and
effectiveness of the improved Raman platform, we carried out bioprospecting for
algal species from soil and marine environments in both temperate and subtropical
geographies to obtain algal isolates from varied environments. Further, we
carried out two rounds of mutagenesis screens on the green algal model species,
Chlamydomonas reinhardtii, to obtain cells with increased lipid content. Analyses
on both environmental isolates and screened cells were conducted which determined
their respective lipids. Different saturation states among the isolates as well
as the screened C. reinhardtii strains were observed. The latter indicated the
presence of cell-to cell variations among cells grown under identical condition.
In contrast, non-mutagenized C. reinhardtii cells showed no significant
heterogeneity in lipid content. CONCLUSIONS: We demonstrate the utility of
confocal Raman microscopy for lipid analysis on novel aquatic and soil microalgal
isolates and for characterization of lipid-expressing cells obtained in a
mutagenesis screen. Raman microscopy enables quantitative determination of the
unsaturation level and chain lengths of microalgal lipids, which are key
parameters in selection and engineering of microalgae for optimal production of
biofuels.
PMID- 26442757
TI - Clinical significance of locoregional and systemic treatment in operable high
risk breast cancer patients with more than four positive axillary lymph nodes.
AB - PURPOSE: Breast cancer cases with four or more involved axillary lymph nodes
(ALNs) feature an aggressive clinical history despite intensive treatment.
However, therapies for improving the prognosis for these high-risk patients and
the prognostic role of clinical characteristics have been little investigated.
Therefore, we sought to assess potential prognostic factors for these patients in
female Chinese patients and identify the treatment modalities they might benefit
from, which offers implications for clinical practice. PATIENTS AND METHODS: A
total of 518 patients with four or more involved ALNs were retrospectively
analyzed. Survival-curve analysis was performed with the Kaplan-Meier method, and
Cox proportional hazard regression was applied to identify independent variables
for disease-free survival (DFS) and overall survival (OS). RESULTS: The patients
were divided into groups depending on the number of ALNs, with 38.22% having four
to six positive ALNs and 61.78% having seven or more ALNs. Compared with the
seven or more-positive ALN subgroup, patients with four to six positive ALNs
tended to have smaller tumors and were more likely to undergo modified radical
mastectomy rather than radical mastectomy (both P<0.001). Univariate analysis
revealed that a fluorouracil/doxorubicin (epirubicin)/cyclophosphamide (CA[E]F)
regimen or a CA(E)F followed by docetaxel (CA[E] F > T) regimen conferred
significantly better DFS (P=0.0075) and OS (P<0.0001) than those achieved from a
cyclophosphamide/methotrexate/fluorouracil regimen, which was almost completely
generated by the seven or more ALN subgroup (P=0.0088 and P=0.0001,
respectively). Postoperative radiotherapy was associated with better DFS
(P=0.0360), which was also generated by the seven or more ALN subgroup
(P=0.0107). Subgroup analysis also clarified that the type of surgery conferred a
modest effect on DFS in the seven or more ALN subgroup (P=0.0305). Multivariate
survival analysis revealed that ALN status (hazard ratio [HR] 2.00, 95%
confidence interval [CI] 1.31-3.05; P=0.001), tumor size (HR 1.48, 95% CI 1.06
2.08; P=0.022), and type of surgery (HR 0.47, 95% CI 0.30-0.74; P=0.001) were
independent prognostic factors for DFS. Meanwhile, ALN status (HR 2.96, 95% CI
1.51-5.77; P=0.002), tumor size (HR 2.32, 95% CI 1.38-3.89; P=0.001), type of
surgery (HR=0.39, 95% CI 0.20-0.76; P=0.006), and regimen of chemotherapy
(HR=0.64, 95% CI 0.50-0.85; P=0.002) were identified as independent prognostic
factors for OS. CONCLUSION: Besides the classical prognostic factors and the
improvement of prognosis achieved from the anthracycline-based or anthracycline
taxane combination chemotherapy compared to
cyclophosphamide/methotrexate/fluorouracil chemotherapy, our findings showed
benefits on DFS and OS for appropriate local treatments, including radiotherapy
and sufficient ALN dissection for high-risk breast cancer patients with four or
more ALNs involved, which suggests that much importance should also be attached
to local treatment besides adjuvant systemic therapy.
PMID- 26442758
TI - Effect of hydro-alcoholic extract of Rosa damascena on cardiovascular responses
in normotensive rat.
AB - OBJECTIVE: Rosa damascena mill L. (R. damascena) is a well-known plant with
fragrant effects. Several therapeutic effects of this plant on respiratory,
gastrointestinal and nervous systems have been reported. It is also suggested to
have beneficial effect on cardiovascular system especially blood pressure
regulation. The present study was carried out to evaluate acute cardiovascular
effect of hydro-alcoholic extract of R. damascena. MATERIALS AND METHODS: Thirty
two male Wistar rats were randomly divided into four groups (n= 8 for each
group). After anesthesia, a catheter was inserted into the femoral artery and
blood pressure and heart rate (HR) were continuously recorded by a power lab
system. Animals received three doses of hydro-alcoholic extract (250, 500, and
1000 mg/kg) via peritoneal (i.p). After 30 min, systolic blood pressure (SBP),
mean arterial pressure (MAP) and HR were recorded and maximal changes were
compared to control group. RESULTS: Injection of all doses of the extract did not
significantly change HR compare to control group. The SBP, dose dependently, was
decreased by all doses of the extract and the maximal response was significant
compared to saline group (p<0.01 to p<0.001). Different doses of the extract also
dose-dependently decreased maximal changes of MAP responses compared to control
group. The effect of higher doses of the extract on SBP and MAP was significant
compared to lower doses (p<0.05 to p<0.01). CONCLUSION: This study provides
evidence of a hypotensive effect of hydro-alcoholic extract of R. damascena with
no significant effect on HR. Therefore, R. damascena is suggested to have
beneficial effect to control blood pressure. However, it needs to be more
investigated.
PMID- 26442760
TI - Interspecific variation in the phenology of advertisement calling in a temperate
Australian frog community.
AB - Spatial and temporal partitioning of resources underlies the coexistence of
species with similar niches. In communities of frogs and toads, the phenology of
advertisement calling provides insights into temporal partitioning of
reproductive effort and its implications for community dynamics. This study
assessed the phenology of advertisement calling in an anuran community from
Melbourne, in southern Australia. We collated data from 1432 surveys of 253 sites
and used logistic regression to quantify seasonality in the nightly probability
of calling and the influence of meteorological variables on this probability for
six species of frogs. We found limited overlap in the predicted seasonal peaks of
calling among these species. Those shown to have overlapping calling peaks are
unlikely to be in direct competition, due to differences in larval ecology
(Crinia signifera and Litoria ewingii) or differences in calling behavior and
acoustics (Limnodynastes dumerilii and Litoria raniformis). In contrast, closely
related and ecologically similar species (Crinia signfera and Crinia
parinsignifera;Litoria ewingii and Litoria verreauxii) appear to have staggered
seasonal peaks of calling. In combination with interspecific variation in the
meteorological correlates of calling, these results may be indicative of temporal
partitioning of reproductive activity to facilitate coexistence, as has been
reported for tropical and temperate anurans from other parts of the globe.
PMID- 26442759
TI - Regional anesthesia for an upper extremity amputation for palliative care in a
patient with end-stage osteosarcoma complicated by a large anterior mediastinal
mass.
AB - Tumor progression during end-of-life care can lead to significant pain, which at
times may be refractory to routine analgesic techniques. Although regional
anesthesia is commonly used for postoperative pain care, there is limited
experience with its use during home hospice care. We present a 24-year-old male
with end-stage metastatic osteosarcoma who required anesthetic care for a right
sided above-the-elbow amputation. The anesthetic management was complicated by
the presence of a large mediastinal mass, limited pulmonary reserve, and severe
chronic pain with a high preoperative opioid requirement. Intraoperative
anesthesia and postoperative pain management were provided by regional anesthesia
using an interscalene catheter. He was discharged home with the interscalene
catheter in place with a continuous local anesthetic infusion that allowed
weaning of his chronic opioid medications and the provision of effective pain
control. The perioperative applications of regional anesthesia in palliative and
home hospice care are discussed.
PMID- 26442761
TI - Cellulosic ethanol production via consolidated bioprocessing at 75 degrees C by
engineered Caldicellulosiruptor bescii.
AB - BACKGROUND: The C. bescii genome does not encode an acetaldehyde/alcohol
dehydrogenase or an acetaldehyde dehydrogenase and no ethanol production is
detected in this strain. The recent introduction of an NADH-dependent AdhE from
C. thermocellum (Fig. 1a) in an ldh mutant of this strain resulted in production
of ethanol from un-pretreated switchgrass, but the thermolability of the C.
thermocellum AdhE at the optimum growth temperature of C. bescii (78 degrees C)
meant that ethanol was not produced above 65 degrees C.Fig. 1Proposed scheme for
the pyruvate to ethanol pathway in C. thermocellum and T. pseudethanolicus 39E. a
The C. thermocellum ethanol pathway. The red colored AdhE (Cthe_0423) is already
expressed and tested in C. bescii [26]. b The T. pseudethanolicus 39E ethanol
pathway. The green colored AdhE (Teth39_0206) and blue colored AdhB (Teth39_0218)
are expressed and tested in C. bescii in this study. RESULTS: The adhB and adhE
genes from Thermoanaerobacter pseudethanolicus 39E, an anaerobic thermophile that
produces ethanol as a major fermentation product at 70 degrees C, were cloned
and expressed in an ldh deletion mutant of C. bescii. The engineered strains
produced ethanol at 75 degrees C, near the ethanol boiling point. The AdhB
expressing strain produced ethanol (1.4 mM on Avicel, 0.4 mM on switchgrass) as
well as acetate (13.0 mM on Avicel, 15.7 mM on switchgrass). The AdhE expressing
strain produced more ethanol (2.3 mM on Avicel, 1.6 mM on switchgrass) and
reduced levels of acetate (12.3 mM on Avicel, 15.1 mM on switchgrass). These
engineered strains produce cellulosic ethanol at the highest temperature of any
microorganism to date. In addition, the addition of 40 mM MOPS to the growth
medium increased the maximal growth yield of C. bescii by approximately twofold.
CONCLUSIONS: The utilization of thermostable enzymes will be critical to
achieving high temperature CBP in bacteria such as C. bescii. The ability to
produce ethanol at 75 degrees C, near its boiling point, raises the possibility
that process optimization could allow in situ product removal of this end product
to mitigate ethanol toxicity.
PMID- 26442762
TI - Correlation between the green-island phenotype and Wolbachia infections during
the evolutionary diversification of Gracillariidae leaf-mining moths.
AB - Internally feeding herbivorous insects such as leaf miners have developed the
ability to manipulate the physiology of their host plants in a way to best meet
their metabolic needs and compensate for variation in food nutritional
composition. For instance, some leaf miners can induce green-islands on yellow
leaves in autumn, which are characterized by photosynthetically active green
patches in otherwise senescing leaves. It has been shown that endosymbionts, and
most likely bacteria of the genus Wolbachia, play an important role in green
island induction in the apple leaf-mining moth Phyllonorycter blancardella.
However, it is currently not known how widespread is this moth-Wolbachia-plant
interaction. Here, we studied the co-occurrence between Wolbachia and the green
island phenotype in 133 moth specimens belonging to 74 species of Lepidoptera
including 60 Gracillariidae leaf miners. Using a combination of molecular
phylogenies and ecological data (occurrence of green-islands), we show that the
acquisitions of the green-island phenotype and Wolbachia infections have been
associated through the evolutionary diversification of Gracillariidae. We also
found intraspecific variability in both green-island formation and Wolbachia
infection, with some species being able to form green-islands without being
infected by Wolbachia. In addition, Wolbachia variants belonging to both A and B
supergroups were found to be associated with green-island phenotype suggesting
several independent origins of green-island induction. This study opens new
prospects and raises new questions about the ecology and evolution of the
tripartite association between Wolbachia, leaf miners, and their host plants.
PMID- 26442763
TI - Long noncoding RNA CCAT2 promotes breast tumor growth by regulating the Wnt
signaling pathway.
AB - In addition to protein-coding genes, the human genome makes a large amount of
noncoding RNAs, including microRNAs and long noncoding RNAs (lncRNAs). Emerging
evidence indicates that lncRNAs could have a critical role in the regulation of
cellular processes such as cell growth and apoptosis as well as cancer
progression and metastasis. The lncRNA CCAT2 is dysregulated in several cancers
such as colon cancer, non-small cell lung cancer, esophageal squamous cell
carcinoma, gastric cancer, and breast cancer; however, the contributions of CCAT2
to breast cancer remain largely unknown. In the current paper, we first confirmed
the high expression level of CCAT2 in breast cancer tissues and breast cancer
cell lines by reverse transcription quantitative polymerase chain reaction (RT
qPCR) assay, and we further analyzed the relationship between CCAT2 expression
and clinical prognostic factors. Also, the biological function of CCAT2 was
explored and the results showed silencing of CCAT2 could suppress cell growth in
vitro and tumor formation in vivo. Finally, our results revealed that the
abnormal expression of CCAT2 could influence the Wnt signaling pathway. In
conclusion, lncRNA CCAT2 might be considered as a novel molecule involved in
breast cancer development, which provides a potential therapeutic target for
breast cancer.
PMID- 26442764
TI - Mitochondrial dysfunction in psychiatric morbidity: current evidence and
therapeutic prospects.
AB - Cumulating evidence for the involvement of mitochondrial dysfunction in
psychiatric disorders leaves little to no doubt regarding the involvement of this
pathology in mood disorders. However, mitochondrial abnormalities are also
observed in a wide range of disorders spanning from cancer and diabetes to
various neurodegenerative and neurodevelopmental disorders such as Parkinson's,
Alzheimer's, Huntington's, autism, and amyotrophic lateral sclerosis. The
apparent lack of specificity questions the role of mitochondrial dysfunction in
psychiatric disorders, in general, and in mood disorders, in particular. Is
mitochondrial dysfunction a general phenomenon, simplistically rendering brain
cells to be more vulnerable to a variety of disease-specific perturbations? Or is
it an epiphenomenon induced by various disease-specific factors? Or possibly, the
severity and the anatomical region of the dysfunction are the ones responsible
for the distinct features of the disorders. Whichever of the aforementioned ones,
if any, is correct, "mitochondrial dysfunction" became more of a cliche than a
therapeutic target. In this review, we summarize current studies supporting the
involvement of mitochondrial dysfunction in different psychiatric disorders. We
address the question of specificity and causality of the different findings and
provide an alternative explanation for some of the aforementioned questions.
PMID- 26442765
TI - Stage susceptibility of Japanese medaka (Oryzias latipes) to selenomethionine and
hypersaline developmental toxicity.
AB - Anthropogenic disturbance of seleniferous soils can lead to selenium
contamination of waterways. Although selenium is an essential micronutrient,
bioaccumulation and maternal transfer of proteinaceous selenomethionine (SeMet)
can result in embryo toxicity. Furthermore, as the climate changes, the salinity
of spawning grounds in water-restrained estuaries is increasing. Although a small
increase in salinity may not directly impact adult fish, it may alter the
detoxification strategies of developing organisms. Previous research indicates
that hypersalinity may potentiate SeMet embryo toxicity at an early developmental
stage. However, embryonic development is a complex, spatiotemporal process with a
constantly shifting cellular microenvironment. To generate thresholds and an
adverse outcome pathway for the interactions between selenium and salinity, we
sought to identify windows of susceptibility for lethality and deformities in the
Japanese medaka (Oryzias latipes). Embryos were treated in freshwater or
saltwater for 24 h with 0.5 uM, 5 uM, and 50 uM SeMet at 6 different
developmental stages (9, 17, 25, 29, 34, and 38). Survival, hatch, deformities
(total, type, and severity), and days to hatch were quantified. Selenium embryo
tissue measurements were performed. Selenomethionine exposures of 5 uM and 50 uM
significantly decreased survival and hatch at all stages. However, SeMet uptake
was stage-dependent and increased with stage. Stage 17 (early neurulation) was
identified as the most susceptible stage for lethality and deformities.
Selenomethionine in saltwater caused significantly greater toxicity than
freshwater at stage 25 (early organogenesis), suggesting a role for liver and
osmoregulatory organogenesis in toxicity.
PMID- 26442766
TI - Is it too cold for Leptospira interrrogans transmission on the Faroese Islands?
AB - Leptospira interrogans is a bacterium that can infect most mammal species. Brown
rats are considered to be one of the most important reservoirs of Leptospira
because they frequently are infected and live in close proximity to humans. Past
studies of prevalence of Leptospira in brown rats indicate that temperature--both
high and low--may negatively affect the prevalence rate in rats, so that
Leptospira is rare or even absent at temperatures below 7-8 degrees C. Here we
investigated the prevalence of infection in brown rats on the Faroese Islands
(mean temperature of 6.5 degrees C) and did not find any infected animals in a
sample of 95 animals. We propose that prevalence rates of Leptospira are very low
in rural brown rats in the cooler Scandinavian regions, even though urban/sewer
rats might be highly infected in the same regions.
PMID- 26442767
TI - Student (dis)engagement and need-supportive teaching behavior: a multi-informant
and multilevel approach.
AB - Starting from self-determination theory, we explored whether student
engagement/disengagement relates to teachers' need support and whether this
relationship is moderated by teachers' causality orientations. A sample of 2004
students situated in 127 classes taught by 33 physical education teachers
participated in the study. Both teachers and students reported on students'
(dis)engagement, allowing investigation of the proposed relationships both at the
student and teacher level. Most of the variance in need support was at the
student level, but there was also between-teacher and between-class variance in
need support. Engagement related to more need support, but only at the student
level. In total, few moderation effects were found. Teachers with a relatively
low controlled orientation were more need supportive when perceiving their
students as emotionally and behaviorally engaged. By making teachers aware of
these dynamics, automatic responses to student engagement can be better thought
out. Recommendations for future research are discussed.
PMID- 26442768
TI - "Mean mugging": an exploration of young Aboriginal women's experiences of
bullying in team sports.
AB - Bullying among youth is rampant and research suggests that young Aboriginal women
may be particularly susceptible to bullying. Sport participation has been
identified as a possible mechanism to prevent bullying behaviors, yet few
researchers have explored bullying within the context of sport. The purpose of
this qualitative description study was to explore young Aboriginal women's
experiences of bullying in team sports. Eight young Aboriginal women participated
in one-on-one semistructured interviews and follow-up phone interviews. Data were
analyzed using a content analysis, and findings were represented by five themes:
(1) mean mugging, (2) sport specific, (3) happens all the time, (4) team bonding
to address bullying, and (5) prevention through active coaches. The detailed
descriptions shared by participants provide insight into a broad range of
bullying experiences and serve as a foundation for addressing the bullying that
occurs in sport.
PMID- 26442769
TI - Dealing with negative stereotypes in sports: the role of cognitive anxiety when
multiple identities are activated in sensorimotor tasks.
AB - Based on research on stereotype threat and multiple identities, this work
explores the beneficial effects of activating a positive social identity when a
negative identity is salient on women's performance in sports. Further, in line
with research on the effects of anxiety in sports, we investigate whether the
activation of a positive social identity buffers performance from cognitive
anxiety associated with a negative stereotype. Two experiments tested these
predictions in field settings. Experiment 1 (N = 83) shows that the simultaneous
activation of a positive (i.e., member of a soccer team) and a negative social
identity (i.e., woman) led to better performance than the activation of only a
negative social identity for female soccer players. Experiment 2 (N = 46)
demonstrates that identity condition moderated the effect of cognitive anxiety on
performance for female basketball players. Results are discussed concerning
multiple identities' potential for dealing with stressful situations.
PMID- 26442770
TI - Changes in task self-efficacy and emotion across competitive performances in
golf.
AB - This research aimed to investigate (a) the effect of golfers' perceptions of
coach motivation efficacy on golfers' precompetition task self-efficacy, (b) the
effect of performance on pre-to-postround changes in self-efficacy, (c) the
effect of pre-to-postround changes in self-efficacy on pre-to-postround changes
in affect and emotion, and (d) whether any effects of performance on pre-to
postcompetition changes in affect and emotion were mediated by pre-to
postcompetition changes in self-efficacy. In Study 1, a scale measuring golf self
efficacy was developed and validated using data from 197 golfers. In Study 2, 200
golfers completed this measure alongside measures of coach motivation efficacy,
and positive and negative affect before a golf competition; all measures (except
coach motivation efficacy) were again completed following the competition.
Structural equation modeling showed that coach motivation efficacy positively
predicted precompetition self-efficacy, performance positively predicted pre-to
postcompetition changes in self-efficacy, which had positive and negative
effects, respectively, on pre-to-postcompetition changes in positive and negative
affect; mediation analyses demonstrated that pre-to-postcompetition changes in
self-efficacy mediated effects of performance on pre-to-postcompetition changes
in positive and negative affect. In Study 3, the Study-2 procedures were
replicated with a separate sample of 212 golfers, except measures of excitement,
concentration disruption, somatic anxiety, and worry replaced those for positive
and negative affect. Structural analyses showed the findings from Study 2 were
largely replicated when specific emotions were investigated in place of general
indices of affect. This investigation makes novel contributions regarding the
potential importance of perceptions of coach efficacy for golfers' own efficacy
beliefs, and the role personal efficacy beliefs may play in facilitating the
effects of performance on affective outcomes.
PMID- 26442771
TI - Bayesian structural equation modeling in sport and exercise psychology.
AB - Bayesian statistics is on the rise in mainstream psychology, but applications in
sport and exercise psychology research are scarce. In this article, the
foundations of Bayesian analysis are introduced, and we will illustrate how to
apply Bayesian structural equation modeling in a sport and exercise psychology
setting. More specifically, we contrasted a confirmatory factor analysis on the
Sport Motivation Scale II estimated with the most commonly used estimator,
maximum likelihood, and a Bayesian approach with weakly informative priors for
cross-loadings and correlated residuals. The results indicated that the model
with Bayesian estimation and weakly informative priors provided a good fit to the
data, whereas the model estimated with a maximum likelihood estimator did not
produce a well-fitting model. The reasons for this discrepancy between maximum
likelihood and Bayesian estimation are discussed as well as potential advantages
and caveats with the Bayesian approach.
PMID- 26442772
TI - Biological evidence of imagery abilities: intraindividual differences.
AB - This study extended motor imagery theories by establishing specificity and
verification of expected brain activation patterns during imagery. Eighteen
female participants screened with the Movement Imagery Questionnaire-3 (MIQ-3) as
having good imagery abilities were scanned to determine the neural networks
active during an arm rotation task. Four experimental conditions (i.e.,
KINESTHETIC, INTERNAL Perspective, EXTERNAL Perspective, and REST) were randomly
presented (counterbalanced for condition) during three brain scans. Behaviorally,
moderate interscale correlations were found between the MIQ-3 and Vividness of
Movement Imagery Questionnaire-2, indicating relatedness between the
questionnaires. Partially confirming our hypotheses, common and distinct brain
activity provides initial biological validation for imagery abilities delineated
in the MIQ-3: kinesthetic imagery activated motor-related areas, internal visual
imagery activated inferior parietal lobule, and external visual imagery activated
temporal, but no occipital areas. Lastly, inconsistent neuroanatomical
intraindividual differences per condition were found. These findings relative to
recent biological evidence of imagery abilities are highlighted.
PMID- 26442773
TI - Development of burnout perceptions during adolescence among high-level athletes:
a developmental and gendered perspective.
AB - This study examined (a) the developmental trajectories of athlete burnout
perceptions, (b) the gender differences on these trajectories, and (c) the
interactions in the developmental trajectories of the three burnout dimensions. A
five-wave longitudinal study was conducted with 895 athletes (47.6% female; Mage
= .67). Results of multilevel growth models revealed that during adolescence,
"reduced sense of accomplishment" linearly decreased and was higher for girls
than boys. Moreover, "emotional/physical exhaustion" increased then decreased,
and seemed to have been attenuated at time points in which athletes also had
higher levels of "sport devaluation." Finally, "sport devaluation" increased over
time with higher increases for girls than boys. Results of our study depicted the
general and the gendered shape of the trajectory of burnout perceptions during
adolescence, and underlined the advantages of considering the multifaceted nature
of burnout to enable a deeper examination of the within-person synergies in the
development of the three dimensions.
PMID- 26442774
TI - Things we still haven't learned (so far).
AB - Null hypothesis significance testing (NHST) is like an immortal horse that some
researchers have been trying to beat to death for over 50 years but without any
success. In this article we discuss the flaws in NHST, the historical background
in relation to both Fisher's and Neyman and Pearson's statistical ideas, the
common misunderstandings of what p < .05 actually means, and the 2010 APA
publication manual's clear, but most often ignored, instructions to report effect
sizes and to interpret what they all mean in the real world. In addition, we
discuss how Bayesian statistics can be used to overcome some of the problems with
NHST. We then analyze quantitative articles published over the past three years
(2012-2014) in two top-rated sport and exercise psychology journals to determine
whether we have learned what we should have learned decades ago about our use and
meaningful interpretations of statistics.
PMID- 26442776
TI - Amphiphilic polymeric micelles as microreactors: improving the photocatalytic
hydrogen production of the [FeFe]-hydrogenase mimic in water.
AB - An amphiphilic polymeric micelle is utilized as a microreactor to load a
hydrophobic [FeFe]-hydrogenase mimic in water. The local concentration
enhancement and strong interaction between the mimic and the photosensitizer as
well as the water-mediated fast proton migration caused by the microreactor
improve photocatalytic hydrogen production remarkably in water.
PMID- 26442777
TI - Impending airway obstruction after dental extractions.
PMID- 26442778
TI - Discovery of wrightiadione as a novel template for the TrkA kinase inhibitors.
AB - Enzymatic kinase assays and docking simulation studies have shown that the
natural product wrightiadione displays inhibitory activity toward TrkA and PLK3.
In this study, the template of wrightiadione served as a starting point for Trk
inhibitor development campaigns. Molecular simulation provided structural
insights for the design of derivatives that were efficiently generated by our
recently developed 3-step tandem synthetic approach, resulting in the discovery
of compound 2h with biochemical potency at the single-digit micromolar level.
PMID- 26442779
TI - Parametric analysis of the biomechanical response of head subjected to the
primary blast loading--a data mining approach.
AB - Traumatic brain injury due to primary blast loading has become a signature injury
in recent military conflicts and terrorist activities. Extensive experimental and
computational investigations have been conducted to study the interrelationships
between intracranial pressure response and intrinsic or 'input' parameters such
as the head geometry and loading conditions. However, these relationships are
very complicated and are usually implicit and 'hidden' in a large amount of
simulation/test data. In this study, a data mining method is proposed to explore
such underlying information from the numerical simulation results. The heads of
different species are described as a highly simplified two-part (skull and brain)
finite element model with varying geometric parameters. The parameters considered
include peak incident pressure, skull thickness, brain radius and snout length.
Their interrelationship and coupling effect are discovered by developing a
decision tree based on the large simulation data-set. The results show that the
proposed data-driven method is superior to the conventional linear regression
method and is comparable to the nonlinear regression method. Considering its
capability of exploring implicit information and the relatively simple
relationships between response and input variables, the data mining method is
considered to be a good tool for an in-depth understanding of the mechanisms of
blast-induced brain injury. As a general method, this approach can also be
applied to other nonlinear complex biomechanical systems.
PMID- 26442780
TI - Eye and pit size are inversely correlated in crotalinae: Implications for
selection pressure relaxation.
AB - Mate, prey, and predator recognition often depend on the integration of
information from multiple sensory modalities including visual, auditory, and/or
olfactory inputs. In Crotalinae, the eyes sense visible light while the pit
organs detect infrared (IR) radiation. Previous studies indicate that there is
significant overlap between the eye and pit sensory fields and that both senses
are involved in recognition processes. This study investigated the relationships
between eye and pit sizes in this taxonomic group as a function of phylogeny and
habitat. In view of the fact that pit orientation depends largely on snout shape,
pit vipers were grouped as follows: 1) arboreal, 2) terrestrial with rounded
snout, and 3) terrestrial with pointed snout. The pit orientations and habitant
patterns were fully independent of the Crotalinae phylogenetic tree. The
phylogenetic generalized least squares model showed that both eye and pit areas
were not of significantly phylogenetic relatedness, implying alternatively a
strong effect of adaptation on eye and pit sizes. Negative correlations between
relative eye and pit areas in terrestrial (both pointed and rounded snouts) and
arboreal species were statistically significant. Our results suggest that the
eyes and pits function in a complementary fashion such that selection for IR
perception relaxes selection pressures on the visual system and selection for
visual discrimination relaxes selection pressures acting on the IR-system.
PMID- 26442782
TI - Label-free detection of pH based on the i-motif using an aggregation-caused
quenching strategy.
AB - A label-free and biocompatible pH sensor system based on the aggregation-caused
quenching (ACQ) probe has been reported herein. The DNA i-motif, a kind of pH
triggered structure, affects the aggregation of PTCDI derivatives by structural
switch that would provide significant fluorescence signals responding to the
different pH values. Our method not only shows sensitive and reversible response
to pH changes, but also could expand the detection range by allosteric control of
the DNA i-motif.
PMID- 26442781
TI - Whole Genome Sequencing demonstrates that Geographic Variation of Escherichia
coli O157 Genotypes Dominates Host Association.
AB - Genetic variation in an infectious disease pathogen can be driven by ecological
niche dissimilarities arising from different host species and different
geographical locations. Whole genome sequencing was used to compare E. coli O157
isolates from host reservoirs (cattle and sheep) from Scotland and to compare
genetic variation of isolates (human, animal, environmental/food) obtained from
Scotland, New Zealand, Netherlands, Canada and the USA. Nei's genetic distance
calculated from core genome single nucleotide polymorphisms (SNPs) demonstrated
that the animal isolates were from the same population. Investigation of the
Shiga toxin bacteriophage and their insertion sites (SBI typing) revealed that
cattle and sheep isolates had statistically indistinguishable rarefaction
profiles, diversity and genotypes. In contrast, isolates from different countries
exhibited significant differences in Nei's genetic distance and SBI typing.
Hence, after successful international transmission, which has occurred on
multiple occasions, local genetic variation occurs, resulting in a global
patchwork of continental and trans-continental phylogeographic clades. These
findings are important for three reasons: first, understanding transmission and
evolution of infectious diseases associated with multiple host reservoirs and
multi-geographic locations; second, highlighting the relevance of the sheep
reservoir when considering farm based interventions; and third, improving our
understanding of why human disease incidence varies across the world.
PMID- 26442783
TI - Light attenuates lipid accumulation while enhancing cell proliferation and starch
synthesis in the glucose-fed oleaginous microalga Chlorella zofingiensis.
AB - The objective of this study was to investigate the effect of light on lipid and
starch accumulation in the oleaginous green algae Chlorella zofingiensis
supplemented with glucose. C. zofingiensis, when fed with 30 g/L glucose,
synthesized lipids up to 0.531 g/g dry weight; while in the presence of light,
the lipid content dropped down to 0.352 g/g dry weight. Lipid yield on glucose
was 0.184 g/g glucose, 14% higher than that cultured with light. The light
mediated lipid reduction was accompanied by the down-regulation of fatty acid
biosynthetic genes at the transcriptional level. Furthermore, light promoted cell
proliferation, starch accumulation, and the starch yield based on glucose. Taken
together, light may attenuate lipid accumulation, possibly through the inhibition
of lipid biosynthetic pathway, leading to more carbon flux from glucose to
starch. This study reveals the dual effects of light on the sugar-fed C.
zofingiensis and provides valuable insights into the possible optimization of
algal biomass and lipid production by manipulation of culture conditions.
PMID- 26442785
TI - Expression of proteins in superior and inferior spikelets of rice during grain
filling under different irrigation regimes.
AB - Poor grain filling of later-flowering inferior spikelets is a serious problem in
modern rice cultivars, but the reason and regulation remain unclear. This study
investigated post-anthesis protein expression in relation with grain filling and
the possibility to use irrigation methods to enhance grain filling through
regulating protein expression. One japonica rice cultivar was field-grown under
three irrigation treatments imposed during the grain filling period: alternate
wetting and moderate soil-drying (WMD), alternate wetting and severe soil-drying
(WSD), and conventional irrigation. High resolution 2DE, combined with MALDI/TOF,
was used to compare differential protein expression between superior and inferior
spikelets. Results showed that the expression of proteins that function in
photosynthesis, carbohydrate and energy metabolism, amino acids metabolism and
defense responses were largely down-regulated in inferior spikelets compared to
those in superior spikelets. The WMD treatment enhanced grain filling rate and
the expression of these proteins, whereas the WSD treatment decreased them.
Similar results were observed for transcript levels of the genes encoding these
proteins. These results suggest that down-regulated expression of the proteins
associated with grain filling contribute to the poor grain filling of inferior
spikelets, and post-anthesis WMD could improve grain filling through regulating
protein expression in the spikelets.
PMID- 26442784
TI - Nerves Control Redox Levels in Mature Tissues Through Schwann Cells and Hedgehog
Signaling.
AB - AIMS: Recent advances in redox biology have emphasized the role of hydrogen
peroxide (H2O2) in the modulation of signaling pathways and revealed that H2O2
plays a role in cellular remodeling in adults. Thus, an understanding of the
mechanisms that control H2O2 levels in mature tissue would be of great interest.
RESULTS: We used a denervation strategy to demonstrate that sensory neurons are
responsible for controlling H2O2 levels under normal conditions and after being
lesioned. Moreover, we demonstrate that severed nerves respond to appendage
amputation via the induction of Hedgehog signaling and that this signaling is
responsible for H2O2 production in the wounded epidermis. Finally, we show that
H2O2 and nerve growth are regulated via reciprocal action in adults. INNOVATION
AND CONCLUSION: These data support a new paradigm for the regulation of tissue
homeostasis: H2O2 attracts nerves and nerves control H2O2 levels in a positive
feedback loop. This finding suggests that the peripheral nerve redox environment
could be a target for manipulating cell plasticity in adults.
PMID- 26442786
TI - Evaluation of four portable blood glucose meters in diabetic and non-diabetic
dogs and cats.
AB - BACKGROUND: Monitoring of an animal's blood glucose concentration is critical for
diagnostic and therapeutic decisions. Over the past few decades, portable blood
glucose meters (PBGMs) have been used to monitor blood glucose concentrations in
animals. Recently, new and improved PBGMs have been made available on the market.
OBJECTIVE: The purpose of this study was to evaluate four PBGMs for use in dogs
and cats. ANIMALS AND METHODS: A total of 155 venous blood samples of dogs and 85
venous blood samples of cats were tested using four PBGMs. Control solutions from
manufacturers were used to determine the precision of each meter. The coefficient
of variation was calculated to determine precision during a set of replicates.
Pearson's correlation analysis, Passing-Bablok regression, and Bland-Altman
analysis were used to determine the accuracy of four PBGMs against the hexokinase
reference method. Error grid analysis was used to evaluate clinical relevance.
RESULTS: All PBGMs, except CERA-PET(r), were clinically acceptable for monitoring
blood glucose concentrations; AlphaTrak(r) and VetMate(r) appeared to be the most
accurate ones, demonstrating that to use PBGMs for glucose monitoring, it is
important to understand the strengths or limitations of each meter. The
difference in results between the PBGMs and the reference method increased at
high glucose concentration ranges, which were also affected by the hematocrit.
CONCLUSIONS: Although readings of the PBGMs and the reference method varied
across glycemic ranges (low, normal, and high glucose concentrations), most PBGMs
were clinically acceptable for monitoring blood glucose concentrations in dogs
and cats.
PMID- 26442787
TI - Platelets made HLA deficient by acid treatment aggregate normally and escape
destruction by complement and phagocytes in the presence of HLA antibodies.
AB - BACKGROUND: The presence of antibodies against HLA Class I can lead to platelet
(PLT) transfusion refractoriness, that is, the repeated failure to achieve
adequate posttransfusion PLT count increments. PLT refractoriness can be overcome
by transfusion of HLA-matched donor PLTs. A different approach is to remove HLA
from the PLT surface using low pH. Previous case studies using HLA-stripped PLTs
showed encouraging but inconsistent results and lacked information on the
biologic effects of acid treatment on PLT function as well as sensitivity to PLT
destruction in the presence of HLA antibodies. STUDY DESIGN AND METHODS: PLTs
prepared from buffy coats were stripped from HLA Class I using a brief incubation
at pH 2.9. Kinetics of acid stripping, viability, phenotypic alterations, and
sensitivity to complement-mediated lysis and phagocytosis were determined by flow
cytometry. Functional potential was evaluated using a multiplate analyzer.
RESULTS: Acid-treated PLTs were viable, upregulated activation markers normally
and aggregated to a similar extent as untreated PLTs in response to stimulation
with three natural agonists. Acid treatment removed 70% to 90% of HLA Class I
complexes from the PLT surface, which led to complete protection from HLA
antibody-mediated complement lysis and reduced monocyte-mediated phagocytosis in
the presence of anti-HLA in vitro. CONCLUSION: Our study fills an important
knowledge gap in how acid treatment affects PLT function and interactions with
immune cells, paving the way for controlled clinical trials to evaluate acid
treated PLTs as an alternative to HLA-matched donors in PLT refractoriness.
PMID- 26442788
TI - Primary care summits.
PMID- 26442790
TI - Multilayer CuO@NiO Hollow Spheres: Microwave-Assisted Metal-Organic-Framework
Derivation and Highly Reversible Structure-Matched Stepwise Lithium Storage.
AB - A unique CuO@NiO microsphere with three-layer ball-in-ball hollow morphology is
successfully synthesized by Cu-Ni bimetallic organic frameworks. The beforehand
facile microwave-assisted production of the Ni organic framework sphere is used
as the template to induce the morphology control of bimetallic oxides. Designed
by the controlled surface cationic exchange reactions between Cu and Ni ions,
there is an elemental gradient (decreased amount of CuO but increased amount of
NiO) from the shell to the core of the microsphere product. This ternary metal
oxide hollow structure is found to be very suitable for solving the critical
volume expansion problem, which is critical for all high-capacity metal oxide
electrodes for lithium ion batteries. A reversible larger-than-theoretical
capacity of 1061 mAh.g(-1) can be retained after a repetitive 200 cycles without
capacity fading compared to the initial cycle. These excellent electrochemical
properties are ascribed to the step-by-step lithium insertion reactions induced
by the matched CuO@NiO composition from the shell to the core and facilitated
lithium/electron diffusion and accommodated volume change in the porous
bimetallic oxides microsphere with a multiple-layer yolk-shell nanostructure.
PMID- 26442789
TI - Secular trends and evaluation of complex interventions: the rising tide
phenomenon.
AB - Evaluations of service delivery interventions with contemporaneous controls often
yield null results, even when the intervention appeared promising in advance.
There can be many reasons for null results. In this paper we introduce the
concept of a 'rising tide' phenomenon being a possible explanation of null
results. We note that evaluations of service delivery interventions often occur
when awareness of the problems they intend to address is already heightened, and
pressure to tackle them is mounting throughout a health system. An evaluation may
therefore take place in a setting where the system as a whole is improving -
where there is a pronounced temporal trend or a 'rising tide causing all vessels
to rise'. As a consequence, control sites in an intervention study will improve.
This reduces the difference between intervention and control sites and
predisposes the study to a null result, leading to the conclusion that the
intervention has no effect. We discuss how a rising tide may be distinguished
from other causes of improvement in both control and intervention groups, and
give examples where the rising tide provides a convincing explanation of such a
finding. We offer recommendations for interpretation of research findings where
improvements in the intervention group are matched by improvements in the control
group. Understanding the rising tide phenomenon is important for a more nuanced
interpretation of null results arising in the context of system-wide improvement.
Recognition that a rising tide may have predisposed to a null result in one
health system cautions against generalising the result to another health system
where strong secular trends are absent.
PMID- 26442791
TI - Shared Medical Decision Making in Lung Cancer Screening: Experienced versus
Descriptive Risk Formats.
AB - BACKGROUND: Annual lung cancer screening using low-dose computed tomography
(LDCT) scans is associated with a survival benefit, but it is also associated
with potential harm. Unlike descriptive probability formats, experienced tasks
have been shown to decrease perceptions of rare events. The objective of this
study was to compare descriptive versus experienced probability formats on
patients' knowledge, beliefs, endorsement of screening for heavy smokers, and
preference (choice predisposition) to undergo screening. METHODS: A total of 276
patients attending an outpatient pulmonary practice were randomized to learn
about screening using 1 of 3 formats: numbers only, numbers + icon arrays,
numbers + a set of slides illustrating LDCT scans of 250 people in random order
that displayed the number of normal scans, false-positive lung nodules, cancers
found leading to a life saved, and cancers found leading to death despite
treatment. RESULTS: Knowledge differed between the 3 formats (P= 0.001), with
participants randomized to the numbers + icon array format having the highest
knowledge score. Beliefs were more favorable among participants randomized to the
numbers + experienced format compared with the numbers + icon array format
(difference between means [95% confidence interval]= 1.6 [0.4-2.8]). Differences
in participants' endorsement of screening (P= 0.4) and choice predisposition (P=
0.6) across probability format mirrored those of beliefs but were not
statistically significant. DISCUSSION: Contrary to what we expected, the
experienced format increased propensity toward screening compared with the
numbers + icon array format, as indicated by more favorable beliefs and
nonsignificant trends toward stronger choice predisposition and endorsement.
Experienced risk formats may not be a practical approach to improve risk
communication for patients deciding whether or not to undergo annual lung cancer
screening.
PMID- 26442792
TI - Genome distribution of differential homoeologue contributions to leaf gene
expression in bread wheat.
AB - Using a combination of de novo transcriptome assembly, a newly developed 9495
marker transcriptome SNP genetic linkage map and comparative genomics approaches,
we developed an ordered set of nonredundant transcripts for each of the
subgenomes of hexaploid wheat: A (47 160 unigenes), B (59 663 unigenes) and D (40
588 unigenes). We used these as reference sequences against which to map Illumina
mRNA-Seq reads derived from young leaf tissue. Transcript abundance was
quantified for each unigene. Using a three-way reciprocal BLAST approach, 15 527
triplet sets of homoeologues (one from each genome) were identified. Differential
expression (P < 0.05) was identified for 5248 unigenes, with 2906 represented at
greater abundance than their two homoeologues and 2342 represented at lower
abundance than their two homoeologues. Analysis of gene ontology terms revealed
no biases between homoeologues. There was no evidence of genomewide dominance
effects, rather the more highly transcribed individual genes were distributed
throughout all three genomes. Transcriptome display tile plot, a visualization
approach based on CMYK colour space, was developed and used to assess the genome
for regions of skewed homoeologue transcript abundance. Extensive striation was
revealed, indicative of many small regions of genome dominance (transcripts of
homoeologues from one genome more abundant than the others) and many larger
regions of genome repression (transcripts of homoeologues from one genome less
abundant than the others).
PMID- 26442793
TI - UV irradiation-induced inflammation, what is the trigger?
PMID- 26442794
TI - Diversity and patterns of interaction of an anuran-parasite network in a
neotropical wetland.
AB - We describe the diversity and structure of a host-parasite network of 11 anuran
species and their helminth parasites in the Pantanal wetland, Brazil.
Specifically, we investigate how the heterogeneous use of space by hosts changes
parasite community diversity, and how the local pool of parasites exploits
sympatric host species of different habits. We examined 229 anuran specimens,
interacting with 32 helminth parasite taxa. Mixed effect models indicated the
influence of anuran body size, but not habit, as a determinant of parasite
species richness. Variation in parasite taxonomic diversity, however, was not
significantly correlated with host size or habit. Parasite community composition
was not correlated with host phylogeny, indicating no strong effect of the
evolutionary relationships among anurans on the similarities in their parasite
communities. Host-parasite network showed a nested and non-modular pattern of
interaction, which is probably a result of the low host specificity observed for
most helminths in this study. Overall, we found host body size was important in
determining parasite community richness, whereas low parasite specificity was
important to network structure.
PMID- 26442795
TI - Protective effect of nitric oxide in aristolochic acid-induced toxic acute kidney
injury: an old friend with new assets.
AB - Aristolochic acid (AA) nephropathy (AAN), a progressive tubulointerstitial injury
of toxic origin, is characterized by early and transient acute tubular necrosis.
This process has been demonstrated to be associated with reduced nitric oxide
(NO) production, which can disrupt the regulation of renal function. In this
study, we tested the hypothesis that L-arginine (L-Arg) supplementation could
restore renal function and reduce renal injury after AA intoxication. C57BL/6 J
male mice were randomly subjected to daily i.p. injection of either sterile
saline solution or AA (2.5 mg kg(-1)) for 4 days. To determine whether AA-induced
renal injuries were linked to reduced NO production, L-Arg, a substrate for NO
synthase, was supplemented (5%) in drinking water. Mice intoxicated with AA
exhibited features of rapid-onset acute kidney injury, including polyuria,
significantly increased plasma creatinine concentrations, proteinuria and
fractional excretion of sodium (P < 0.05), along with severe proximal tubular
cell injury and increased NADPH oxidase 2 (Nox2)-derived oxidative stress (P <
0.05). This was associated with a significant reduction in NO bioavailability. L
Arg supplementation in AA-treated mice significantly increased NO
bioavailability, which in turn improved renal function (creatininaemia, polyuria,
proteinuria, fractional excreted sodium and N-acetyl-beta-D-glucosaminidase
enzymuria) and renal structure (tubular necrosis and tubular cell apoptosis).
These changes were associated with significant reductions in Nox2 expression and
in production of reactive oxygen species and with an increase in antioxidant
concentrations. Our results demonstrate that preservation of NO bioavailability
leads to renal protection in AA-induced acute kidney injury by reducing oxidative
stress and maintaining renal function.
PMID- 26442796
TI - A three-dimensional spin-diffusion model for micromagnetics.
AB - We solve a time-dependent three-dimensional spin-diffusion model coupled to the
Landau-Lifshitz-Gilbert equation numerically. The presented model is validated by
comparison to two established spin-torque models: The model of Slonzewski that
describes spin-torque in multi-layer structures in the presence of a fixed layer
and the model of Zhang and Li that describes current driven domain-wall motion.
It is shown that both models are incorporated by the spin-diffusion description,
i.e., the nonlocal effects of the Slonzewski model are captured as well as the
spin-accumulation due to magnetization gradients as described by the model of
Zhang and Li. Moreover, the presented method is able to resolve the time
dependency of the spin-accumulation.
PMID- 26442797
TI - Re(I) derivatives functionalised with thioether crowns containing the 1,10
phenanthroline subunit as a new class of chemosensors.
AB - A series of luminescent fac-[Re(CO)3(L)(NN)](+) complexes, where L is a pyridine
or an imidazole and NN is the 1,10-phenanthroline subunit of mixed donor
pentadentate thioether crowns have been synthesised and their luminescence
properties have been analysed. Then, heterometallic Re(i)/Au(i) complexes, with
the Au(i) fragment bonded directly to the imidazole ligand, and heterometallic
Re(i)/Ag(i) complexes, with the silver fragment coordinating the S-donor
thioether linker of the rings have also been prepared. Analysis of their
luminescence properties showed a considerable blue shift of the emission maxima
for the Re(i)/Ag(i) derivatives, upon coordination of the silver centre to the S
donor atoms of the aliphatic chain of the macrocyclic units.
PMID- 26442798
TI - In Vivo Contact Characteristics of Distal Radioulnar Joint With Malunited Distal
Radius During Wrist Motion.
AB - PURPOSE: To determine whether distal radioulnar joint (DRUJ) contact
characteristics were altered in patients with malunited distal radius fractures.
METHODS: We obtained computed tomography scans at 5 positions of both wrists of 6
patients who had unilateral malunited distal radius fractures with dorsal
angulation from 10 degrees to 20 degrees and ulnar variance less than 3 mm. We
reconstructed 3-dimensional images and mapped contact regions of DRUJ by
calculating the shortest distance between the 2 opposing bones. The contact areas
of the DRUJ were measured and the contact region centers were calculated and
analyzed. The values of the malunited side were compared with those of the
contralateral uninjured side. RESULTS: In the uninjured wrist, the contact areas
of the DRUJ increased slightly from wrist flexion to extension and ulnar
deviation. In the malunited wrist, we found the contact areas of DRUJ to be
progressively reduced from 20 degrees flexion to neutral, 40 degrees extension,
and 20 degrees extension, to ulnar deviation. The centroid of this area on the
sigmoid notch moved to distal from flexion to extension. Compared with the
contralateral uninjured wrist, the contact area significantly decreased during
wrist extension and ulnar deviation, and significantly increased during wrist
flexion. The centroids of this area on sigmoid notch all moved volarly in all
selected wrist positions. CONCLUSIONS: The contact areas of the DRUJ and the
centroid of contact area on sigmoid notch are altered in patients with malunited
distal radius fractures. The contact area of the DRUJ increases during wrist
flexion and decreases during wrist extension and ulnar deviation. The centroids
of the contact area on sigmoid notch move volarly during wrist flexion-extension
and ulnar deviation. CLINICAL RELEVANCE: The in vivo findings suggest that
alterations in joint mechanics may have an important role in the dysfunction
associated with these injuries.
PMID- 26442799
TI - Gene Therapy for Heart Failure: Back to the Bench.
PMID- 26442802
TI - Emerging Roles of tRNA-derived Fragments in Viral Infections: The Case of
Respiratory Syncytial Virus.
PMID- 26442803
TI - Strain-dependent Lethal Toxicity in NKG2D Ligand-targeted CAR T-cell Therapy.
PMID- 26442804
TI - Vertigo with dysautonomia and serious allergy: An unusual case of juvenile
Meniere's disease.
AB - A 13-year-old boy with frequent episodes of vertigo and otologic symptoms was
diagnosed with Meniere's disease (MD) but failed to respond to conventional
treatment. Allergy testing revealed serious reactions to many allergens, and
autonomic tests showed he was dysautonomic. An allergen-restricted diet and
treatment of dysautonomia were effective, the boy being free from vertigo within
2 months. This case provides evidence to promote the understanding of MD in
children. The authors hypothesize that the autonomic nerves and the immune system
can interact, and that such an interaction of dysautonomia and allergy can lead
to a serious vertigo episode.
PMID- 26442806
TI - Clogging of granular materials in silos: effect of gravity and outlet size.
AB - By means of extensive numerical simulations we disclose the role of the driving
force in the clogging of inert particles passing through a constriction. We
uncover the effect of gravity and outlet size on the flow rate and kinetic energy
within the system, and use these quantities to deepen our understanding of the
blocking process. First, we confirm the existence of a finite avalanche size when
the driving force tends to zero. The magnitude of this limit avalanche size grows
with the outlet size, as expected due to geometrical reasons. In addition, there
is an augment of the avalanche size when the driving force is increased, an
effect that is enhanced by the outlet size. This phenomenology is explained by
assuming that in order to get a stable clog developed, two conditions must be
fulfilled: (1) an arch spanning the outlet size should be formed; (2) the arch
should resist until the complete dissipation of the kinetic energy within the
system. From these assumptions, we are able to obtain the probability that an
arch gets destabilized, which is shown to primarily depend on the square root of
the kinetic energy. A minor additional dependence of the outlet size is also
observed which is explained in the light of recent results of the arch resistance
in vibrated silos.
PMID- 26442805
TI - Development of Planning in Children with High-Functioning Autism Spectrum
Disorders and/or Attention Deficit/Hyperactivity Disorder.
AB - Planning impairment is often observed in children with high-functioning autism
spectrum disorders (ASD), but attempts to differentiate planning in ASD from
children with attention deficit hyperactivity disorder (ADHD) and typically
developing children (TD) have yielded inconsistent results. This study examined
differences between these groups by focusing on development and analyzing
performance in searching ahead several steps ("search depth") in addition to
commonly used global performance measures in planning. A cross-sectional
consecutive sample of 83 male patients (6-13 years), subgrouped as ASD without
(ASD-, n = 18) or with comorbid ADHD (ASD+, n = 23), ADHD only (n = 42) and n =
42 TD children (6-13 years) were tested with the Tower-of-London-task. For global
performance, ASD+ showed the lowest accuracy in younger children, but similar
performance as TD at older ages, suggesting delayed development. Typically, a
prolongation of planning time with increasing problem difficulty is observed in
older children as compared to younger children. Here, this was most pronounced in
ASD-, but under-expressed in ADHD. In contrast to global performance, effects of
search depth were independent of age. ASD-, but not ASD+, showed increased
susceptibility to raised demands on mentally searching ahead, along with the
longest planning times. Thus, examining both global and search depth performance
across ages revealed discernible patterns of planning between groups. Notably,
the potentially detrimental impact of two diagnosed disorders does not add up in
ASD+ in this task. Rather, our results suggest paradoxical enhancement of
performance, ostensibly attributable to disruption of behavioral rigidity through
increased impulsivity, which did not take place in ASD-. Autism Res 2016, 9: 739
751. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 26442807
TI - Volcanic passive margins: another way to break up continents.
AB - Two major types of passive margins are recognized, i.e. volcanic and non
volcanic, without proposing distinctive mechanisms for their formation. Volcanic
passive margins are associated with the extrusion and intrusion of large volumes
of magma, predominantly mafic, and represent distinctive features of Larges
Igneous Provinces, in which regional fissural volcanism predates localized syn
magmatic break-up of the lithosphere. In contrast with non-volcanic margins,
continentward-dipping detachment faults accommodate crustal necking at both
conjugate volcanic margins. These faults root on a two-layer deformed ductile
crust that appears to be partly of igneous nature. This lower crust is exhumed up
to the bottom of the syn-extension extrusives at the outer parts of the margin.
Our numerical modelling suggests that strengthening of deep continental crust
during early magmatic stages provokes a divergent flow of the ductile lithosphere
away from a central continental block, which becomes thinner with time due to the
flow-induced mechanical erosion acting at its base. Crustal-scale faults dipping
continentward are rooted over this flowing material, thus isolating micro
continents within the future oceanic domain. Pure-shear type deformation affects
the bulk lithosphere at VPMs until continental breakup, and the geometry of the
margin is closely related to the dynamics of an active and melting mantle.
PMID- 26442808
TI - Is emotional intelligence relevant to a fighting force?
AB - Over the past decade, the expectations of what the fighting force are tasked to
deal with has changed significantly. The high-risk, high-tempo operational
environments in which personnel have deployed in recent years have been complex
and diverse, creating a spectrum of conflict where having EI would be an
essential attribute. EI could be beneficial for the organisation and the
individuals involved, and historically, there has been a distinct lack of EI. For
it to be better used within the military, the entire concept needs to be
explored, accepted and integrated into training throughout the rank structure;
from the recruitment process to throughout the career development with support
from senior commanders. This article discusses the relevance of emotional
intelligence (EI) to the British Armed Forces.
PMID- 26442809
TI - Proteolytic degradation of neuropeptide Y (NPY) from head to toe: Identification
of novel NPY-cleaving peptidases and potential drug interactions in CNS and
Periphery.
AB - The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with
respect to receptor selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or
proteolytic degraded by neprilysin or meprins, thereby abrogating signal
transduction. However, neither the subcellular nor the compartmental
differentiation of these regulatory mechanisms is fully understood. Using mass
spectrometry, selective inhibitors and histochemistry, studies across various
cell types, body fluids, and tissues revealed that most frequently DP4-like
enzymes, aminopeptidases P, secreted meprin-A (Mep-A), and cathepsin D (CTSD)
rapidly hydrolyze NPY, depending on the cell type and tissue under study. Novel
degradation of NPY by cathepsins B, D, L, G, S, and tissue kallikrein could also
be identified. The expression of DP4, CTSD, and Mep-A at the median eminence
indicates that the bioactivity of NPY is regulated by peptidases at the
interphase between the periphery and the CNS. Detailed ex vivo studies on human
sera and CSF samples recognized CTSD as the major NPY-cleaving enzyme in the CSF,
whereas an additional C-terminal truncation by angiotensin-converting enzyme
could be detected in serum. The latter finding hints to potential drug
interaction between antidiabetic DP4 inhibitors and anti-hypertensive angiotensin
converting enzyme inhibitors, while it ablates suspected hypertensive side
effects of only antidiabetic DP4-inhibitors application. The bioactivity of
neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor
selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or proteolytic degraded
by neprilysin or meprins, thereby abrogating signal transduction. However,
neither the subcellular nor the compartmental differentiation of these regulatory
mechanisms is fully understood. Using mass spectrometry, selective inhibitors and
histochemistry, studies across various cell types, body fluids, and tissues
revealed that most frequently DP4-like enzymes, aminopeptidases P, secreted
meprin-A (Mep-A), and cathepsin D (CTSD) rapidly hydrolyze NPY, depending on the
cell type and tissue under study. Novel degradation of NPY by cathepsins B, D, L,
G, S, and tissue kallikrein could also be identified. The expression of DP4,
CTSD, and Mep-A at the median eminence indicates that the bioactivity of NPY is
regulated by peptidases at the interphase between the periphery and the CNS.
Detailed ex vivo studies on human sera and CSF samples recognized CTSD as the
major NPY-cleaving enzyme in the CSF, whereas an additional C-terminal truncation
by angiotensin-converting enzyme could be detected in serum. The latter finding
hints to potential drug interaction between antidiabetic DP4 inhibitors and anti
hypertensive angiotensin-converting enzyme inhibitors, while it ablates suspected
hypertensive side effects of only antidiabetic DP4-inhibitors application.
PMID- 26442810
TI - Interpersonal sensitivity, coping ways and automatic thoughts of nursing students
before and after a cognitive-behavioral group counseling program.
AB - BACKGROUND: In order to provide optimal professional care to patients, nurses
must possess a positive self-image and professional identity. High interpersonal
sensitivity, coping problems and dysfunctional automatic thoughts can prevent
nursing students to be self-confident and successful nurses. Helping nursing
students experiencing interpersonal sensitivity problems via cognitive-behavioral
counseling strategies can contribute to shape good nurses. OBJECTIVES: This study
aims to evaluate interpersonal sensitivity, ways of coping and automatic thoughts
of nursing students before and after a cognitive behavioral group counseling
program. DESIGN: An intervention study with 43 nursing students. Measurements
were done before the counseling program, at the end of the program and 4.5months
after the program. SETTINGS: The students were chosen from a faculty of nursing
in Turkey. PARTICIPANTS: 43 second and third year nursing students who were
experiencing interpersonal sensitivity problems constituted the sample. METHODS:
Brief Symptom Inventory, Ways of Coping Inventory and Automatic Thoughts
Questionnaire were used for data collection. RESULTS: The students' scores of
"interpersonal sensitivity", "hopeless" and "submissive" copings and "automatic
thoughts" were significantly lower at the end of and 4.5months after the program
than the scores before the program (Interpersonal sensitivity F=52.903, p=0.001;
hopeless approach F=19.213, p=0.001; submissive approach F=4.326, p=0.016;
automatic thoughts F=45.471, p=0.001). Scores of "self-confident", "optimistic"
and "seeking social support" copings were higher at the end of and 4.5months
after the program than the scores before the program (Self confident F=11.640,
p=0.001; optimistic F=10.860, p=0.001; seeking social support F=10.411, p=0.001).
CONCLUSIONS: This program helped the students to have better results at
interpersonal sensitivity, ways of coping and automatic thoughts at the end of
and 4.5 months after the program. We have reached the aim of the study. We
suggest that such counseling programs should be regular and integrated into the
services provided for students.
PMID- 26442811
TI - Baton pass hypothesis: successive incorporation of unconserved endogenous
retroviral genes for placentation during mammalian evolution.
AB - It is well accepted that numerous RNAs derived from endogenous retroviruses
(ERVs) are expressed in mammalian reproductive structures, particularly in the
uterus, trophoblast, and placenta. Syncytin 1 and syncytin 2 in humans and
syncytin A and syncytin B in mice are membrane proteins originating from Env
genes of ERVs. These ERVs are involved in the fusion of trophoblast cells,
resulting in multinucleated syncytiotrophoblast formation. Evidence accumulated
indicates that syncytin-like fusogenic proteins are expressed in the placenta of
rabbits, dogs/cats, ruminant ungulates, tenrecs, and opossums. The syncytin genes
so far characterized are known to be endogenized to the host genome only within
the past 12-80 million years, more recently than the appearance of mammalian
placentas, estimated to be 160-180 million years ago. We speculate that ERVs
including syncytin-like gene variants integrated into mammalian genomes in a
locus-specific manner have replaced the genes previously responsible for cell
fusion. We therefore propose the 'baton pass' hypothesis, in which multiple
successive ERV variants 'take over' cell-fusion roles, resulting in increased
trophoblast cell fusion, morphological variations in placental structures, and
enhanced reproductive success in placental mammals.
PMID- 26442812
TI - Radiographic osteoradionecrosis of the jaw with intact mucosa: Proposal of
clinical guidelines for early identification of this condition.
PMID- 26442813
TI - Malignant peripheral nerve sheath tumors of the head and neck: Demographics,
clinicopathologic features, management, and treatment outcomes.
AB - OBJECTIVES: To determine the epidemiology and prognostic indicators in patients
with malignant peripheral nerve sheath tumors (MPNST) of the head and neck.
MATERIALS AND METHODS: The surveillance, epidemiology, and end results registry
was reviewed for patients with head and neck MPNST from 1973 to 2011. Study
variables included age, sex, race, tumor size, stage at presentation, and
treatment modality. RESULTS: There were 374 cases of head and neck MPNST
identified. Mean age at diagnosis was 50.7 y ears; 60.2% of patients were male
and 82.6% were white. After diagnosis, 38.8% of patients underwent surgery and
radiation therapy and 48.1% underwent surgery alone. Kaplan-Meier analysis
demonstrated overall (OS) and disease-specific survival (DSS) of 51% and 67% at 5
years. Multivariate Cox regression analysis showed that age (p=0.030), stage
(p=0.002), surgery (p=0.037), and size (p<0.001) were predictors of OS, while
stage (p<0.001) and size (p<0.001) were predictors of DSS. For stage I/II
cancers, surgery (p=0.011) and size (p=0.010) were predictors of OS, and size
(p=0.001) predicted DSS. For stage III/IV cancers, both radiotherapy (p=0.024,
p=0.009) and size (p=0.001, p=0.001) predicted OS and DSS. For tumors ?5 cm,
stage (p=0.031) predicted DSS. For tumors >5 cm, male gender (p=0.005), stage
(p=0.001), surgery (p=0.003), and radiotherapy (p=0.050) were determinants of OS,
and male gender (p=0.022), stage (p<0.001), and radiotherapy (p=0.002) were
determinants of DSS. CONCLUSION: Surgical resection confers survival benefit in
patients with early stage MPNST, while radiotherapy improves survival in cases
with metastatic disease. Surgery and radiotherapy are prognostically important in
patients with tumors >5 cm.
PMID- 26442815
TI - What Will a Post-Aging World Really Be Like? Finally, A Tool to Help Us Predict.
PMID- 26442814
TI - Energetics of proton release on the first oxidation step in the water-oxidizing
enzyme.
AB - In photosystem II (PSII), the Mn4CaO5 cluster catalyses the water splitting
reaction. The crystal structure of PSII shows the presence of a hydrogen-bonded
water molecule directly linked to O4. Here we show the detailed properties of the
H-bonds associated with the Mn4CaO5 cluster using a quantum mechanical/molecular
mechanical approach. When O4 is taken as a MU-hydroxo bridge acting as a hydrogen
bond donor to water539 (W539), the S0 redox state best describes the unusually
short O4-OW539 distance (2.5 A) seen in the crystal structure. We find that in
S1, O4 easily releases the proton into a chain of eight strongly hydrogen-bonded
water molecules. The corresponding hydrogen-bond network is absent for O5 in S1.
The present study suggests that the O4-water chain could facilitate the initial
deprotonation event in PSII. This unexpected insight is likely to be of real
relevance to mechanistic models for water oxidation.
PMID- 26442816
TI - Determination of emerging contaminants in wastewater utilizing comprehensive two
dimensional gas-chromatography coupled with time-of-flight mass spectrometry.
AB - An analytical method for identification of emerging contaminants of concern, such
as pesticides and organohalogens has been developed and utilized for true
discovery-based analysis. In order to achieve the level of sensitivity and
selectivity necessary for detecting compounds in complex samples, comprehensive
gas chromatography coupled with time-of-flight mass spectrometry (GC*GC-TOFMS)
was utilized to analyze wastewater samples obtained from the Pennsylvania State
University wastewater treatment facility (WWTF). Determination of emerging
contaminants through a process of combining samples which represent "normal
background" and comparing this to new samples was developed. Results show the
presence of halogenated benzotriazoles in wastewater samples as well as soil
samples from Pennsylvania State University agricultural fields. The trace levels
of chlorinated benzotriazoles observed in the monitoring wells present on the
property indicate likely environmental degradation of the chlorinated
benzotriazoles. Preliminary investigation of environmental fate of the
substituted benzotriazoles indicates their likely degradation into phenol; an
Environmental Protection Agency (USEPA) priority pollutant.
PMID- 26442817
TI - Ca(2+) signals mediated by bradykinin type 2 receptors in normal pancreatic
stellate cells can be inhibited by specific Ca(2+) channel blockade.
AB - KEY POINTS: Bradykinin may play a role in the autodigestive disease acute
pancreatitis, but little is known about its pancreatic actions. In this study, we
have investigated bradykinin-elicited Ca(2+) signal generation in normal mouse
pancreatic lobules. We found complete separation of Ca(2+) signalling between
pancreatic acinar (PACs) and stellate cells (PSCs). Pathophysiologically relevant
bradykinin concentrations consistently evoked Ca(2+) signals, via B2 receptors,
in PSCs but never in neighbouring PACs, whereas cholecystokinin, consistently
evoking Ca(2+) signals in PACs, never elicited Ca(2+) signals in PSCs. The
bradykinin-elicited Ca(2+) signals were due to initial Ca(2+) release from
inositol trisphosphate-sensitive stores followed by Ca(2+) entry through Ca(2+)
release-activated channels (CRACs). The Ca(2+) entry phase was effectively
inhibited by a CRAC blocker. B2 receptor blockade reduced the extent of PAC
necrosis evoked by pancreatitis-promoting agents and we therefore conclude that
bradykinin plays a role in acute pancreatitis via specific actions on PSCs.
ABSTRACT: Normal pancreatic stellate cells (PSCs) are regarded as quiescent, only
to become activated in chronic pancreatitis and pancreatic cancer. However, we
now report that these cells in their normal microenvironment are far from
quiescent, but are capable of generating substantial Ca(2+) signals. We have
compared Ca(2+) signalling in PSCs and their better studied neighbouring acinar
cells (PACs) and found complete separation of Ca(2+) signalling in even closely
neighbouring PACs and PSCs. Bradykinin (BK), at concentrations corresponding to
the slightly elevated plasma BK levels that have been shown to occur in the auto
digestive disease acute pancreatitis in vivo, consistently elicited substantial
Ca(2+) signals in PSCs, but never in neighbouring PACs, whereas the physiological
PAC stimulant cholecystokinin failed to evoke Ca(2+) signals in PSCs. The BK
induced Ca(2+) signals were mediated by B2 receptors and B2 receptor blockade
protected against PAC necrosis evoked by agents causing acute pancreatitis. The
initial Ca(2+) rise in PSCs was due to inositol trisphosphate receptor-mediated
release from internal stores, whereas the sustained phase depended on external
Ca(2+) entry through Ca(2+) release-activated Ca(2+) (CRAC) channels. CRAC
channel inhibitors, which have been shown to protect PACs against damage caused
by agents inducing pancreatitis, therefore also inhibit Ca(2+) signal generation
in PSCs and this may be helpful in treating acute pancreatitis.
PMID- 26442818
TI - Assessing the Pathogenicity of Insertion and Deletion Variants with the Variant
Effect Scoring Tool (VEST-Indel).
AB - Insertion/deletion variants (indels) alter protein sequence and length, yet are
highly prevalent in healthy populations, presenting a challenge to bioinformatics
classifiers. Commonly used features--DNA and protein sequence conservation, indel
length, and occurrence in repeat regions--are useful for inference of protein
damage. However, these features can cause false positives when predicting the
impact of indels on disease. Existing methods for indel classification suffer
from low specificities, severely limiting clinical utility. Here, we further
develop our variant effect scoring tool (VEST) to include the classification of
in-frame and frameshift indels (VEST-indel) as pathogenic or benign. We apply 24
features, including a new "PubMed" feature, to estimate a gene's importance in
human disease. When compared with four existing indel classifiers, our method
achieves a drastically reduced false-positive rate, improving specificity by as
much as 90%. This approach of estimating gene importance might be generally
applicable to missense and other bioinformatics pathogenicity predictors, which
often fail to achieve high specificity. Finally, we tested all possible meta
predictors that can be obtained from combining the four different indel
classifiers using Boolean conjunctions and disjunctions, and derived a meta
predictor with improved performance over any individual method.
PMID- 26442819
TI - Management of foveal adhesion of a dexamethasone implant.
PMID- 26442820
TI - Coordinating ecological risk assessment with natural resource damage assessment:
A panel discussion.
AB - Contaminated sites in the United States undergo remediation and restoration
through regulatory programs that lead the 2 processes through independent but
often parallel pathways with different objectives. The objective of remediation
is to reduce risk to human health and the environment, whereas that of
restoration is to restore injured resources and compensate the public for lost
use of the services that natural resources provide. More complex sites, such as
those associated with large river systems and urban waterways, have resulted in
increasingly larger-scale ecological risk assessments (ERAs) and natural resource
damage assessments (NRDAs) that take many years and involve diverse practitioners
including scientists, economists, and engineers. Substantial levels of effort are
now frequently required, creating a need for more efficient and cost-effective
approaches to data collection, analyses, and assessments. Because there are
commonalities in the data needs between ERAs and NRDAs, coordination of the
design and implementation of site-specific studies that meet the needs of both
programs could result in increased efficiency and lower costs. The Association
for Environmental Health and Sciences Foundation convened a panel of
environmental practitioners from industry, consulting, and regulatory bodies to
examine the benefits and challenges associated with coordinating ERA and NRDA
activities in the context of a broad range of regulatory programs. This brief
communication presents the opinions and conclusions of the panelists on these
issues and reports 2 case studies for which coordinated ERA and NRDA activities
produced a positive outcome. Integr Environ Assess Manag 2016;12:616-621. (c)
2015 SETAC.
PMID- 26442821
TI - Growing evidence that maternal gestational diabetes increases risk of autism in
offspring.
PMID- 26442822
TI - Antitumor Activity of Garcinol in Human Prostate Cancer Cells and Xenograft Mice.
AB - Garcinol, which is isolated from fruit rinds of Garcinia indica, is a
polyisoprenylated benzophenone. It has been studied for its antitumor activity by
inducing apoptosis and inhibiting autophagy in human prostate cancer cells. The
Bax/Bcl-2 ratio increased when garcinol was applied to PC-3 cells indicating a
presence of apoptosis. Meanwhile, procaspases-9 and -3 were suppressed with
attenuating PARP and DFF-45. Autophagy was inhibited through activating p-mTOR
and p-PI3 Kinase/AKT by garcinol, which as a result induced the cells to
apoptosis directly. In addition, the apoptosis effect of garcinol in a xenograft
mouse model was also tested, suggesting a consistent result with PC-3 cell model.
The tumor size was reduced more than 80 percent after the mouse accepted the
garcinol treatment. Garcinol was demonstrated to have a strong antitumor activity
through inhibiting autophagy and inducing apoptosis, which was discovered for the
first time. Based on these findings, our data suggests that garcinol deserves
further investigation as a potent chemopreventive agent.
PMID- 26442824
TI - Invasive Salmonellosis in Humans.
AB - Human salmonellosis is generally associated with Salmonella enterica from
subspecies enterica (subspecies I). Acute infections can present in one of four
ways: enteric fever, gastroenteritis, bacteremia, or extraintestinal focal
infection. As with other infectious diseases, the course and outcome of the
infection depend on a variety of factors, including the infecting organism, the
inoculating dose, and the immune status and genetic background of the host. For
serovarsTyphi and Paratyphi A there is a clear association between the genetic
background of the serovar and systemic infection in humans. For serovars
Paratyphi B and Paratyphi C, a good clinical description of the host and detailed
population genetics of the pathogen are necessary before more detailed genetic
studies of novel virulence factors,or host factors,can be initiated. For the
nontyphoidalserovars (NTS) the situation is less clear. Serovars Typhimurium and
Enteritidis are the most common within the food chain, and so the large number of
invasive infections associated with these serovars is most likely due to exposure
rather than to increased virulence of the pathogen. In Africa, however, a closely
related group of strains of serovar Typhimurium, associated with HIV infection,
may have become host adapted tohumans, suggesting that not all isolates called
"Typhimurium" should be considered as a single group. Here we review current
knowledge of the salmonellae for which invasive disease in humans is an important
aspect of their population biology.
PMID- 26442825
TI - Aminoacyl-tRNA Synthetases in the Bacterial World.
AB - Aminoacyl-tRNAsynthetases (aaRSs) are modular enzymesglobally conserved in the
three kingdoms of life. All catalyze the same two-step reaction, i.e., the
attachment of a proteinogenic amino acid on their cognate tRNAs, thereby
mediating the correct expression of the genetic code. In addition, some aaRSs
acquired other functions beyond this key role in translation.Genomics and X-ray
crystallography have revealed great structural diversity in aaRSs (e.g.,in
oligomery and modularity, in ranking into two distinct groups each subdivided in
3 subgroups, by additional domains appended on the catalytic modules). AaRSs show
hugestructural plasticity related to function andlimited idiosyncrasies that are
kingdom or even speciesspecific (e.g.,the presence in many Bacteria of non
discriminating aaRSs compensating for the absence of one or two specific aaRSs,
notably AsnRS and/or GlnRS).Diversity, as well, occurs in the mechanisms of aaRS
gene regulation that are not conserved in evolution, notably betweendistant
groups such as Gram-positive and Gram-negative Bacteria.Thereview focuses on
bacterial aaRSs (and their paralogs) and covers their structure, function,
regulation,and evolution. Structure/function relationships are emphasized,
notably the enzymology of tRNA aminoacylation and the editing mechanisms for
correction of activation and charging errors. The huge amount of genomic and
structural data that accumulatedin last two decades is reviewed,showing how
thefield moved from essentially reductionist biologytowards more global and
integrated approaches. Likewise, the alternative functions of aaRSs and those of
aaRSparalogs (e.g., during cellwall biogenesis and other metabolic processes in
or outside protein synthesis) are reviewed. Since aaRS phylogenies present
promiscuous bacterial, archaeal, and eukaryal features, similarities and
differences in the properties of aaRSs from the three kingdoms of life are
pinpointedthroughout the reviewand distinctive characteristics of bacterium-like
synthetases from organelles are outlined.
PMID- 26442826
TI - Homologous Recombination-Enzymes and Pathways.
AB - Homologous recombination is an ubiquitous process that shapes genomes and repairs
DNA damage. The reaction is classically divided into three phases: presynaptic,
synaptic, and postsynaptic. In Escherichia coli, the presynaptic phase involves
either RecBCD or RecFOR proteins, which act on DNA double-stranded ends and DNA
single-stranded gaps, respectively; the central synaptic steps are catalyzed by
the ubiquitous DNA-binding protein RecA; and the postsynaptic phase involves
either RuvABC or RecG proteins, which catalyze branch-migration and, in the case
of RuvABC, the cleavage of Holliday junctions. Here, we review the biochemical
properties of these molecular machines and analyze how, in light of these
properties, the phenotypes of null mutants allow us to define their biological
function(s). The consequences of point mutations on the biochemical properties of
recombination enzymes and on cell phenotypes help refine the molecular mechanisms
of action and the biological roles of recombination proteins. Given the high
level of conservation of key proteins like RecA and the conservation of the
principles of action of all recombination proteins, the deep knowledge acquired
during decades of studies of homologous recombination in bacteria is the
foundation of our present understanding of the processes that govern genome
stability and evolution in all living organisms.
PMID- 26442823
TI - Translesion DNA Synthesis.
AB - All living organisms are continually exposed to agents that damage their DNA,
which threatens the integrity of their genome. As a consequence, cells are
equipped with a plethora of DNA repair enzymes to remove the damaged DNA.
Unfortunately, situations nevertheless arise where lesions persist, and these
lesions block the progression of the cell's replicase. In these situations, cells
are forced to choose between recombination-mediated "damage avoidance" pathways
or a specialized DNA polymerase (pol) to traverse the blocking lesion. The latter
process is referred to as Translesion DNA Synthesis (TLS). As inferred by its
name, TLS not only results in bases being (mis)incorporated opposite DNA lesions
but also bases being (mis)incorporated downstream of the replicase-blocking
lesion, so as to ensure continued genome duplication and cell survival.
Escherichia coli and Salmonella typhimurium possess five DNA polymerases, and
while all have been shown to facilitate TLS under certain experimental
conditions, it is clear that the LexA-regulated and damage-inducible pols II, IV,
and V perform the vast majority of TLS under physiological conditions. Pol V can
traverse a wide range of DNA lesions and performs the bulk of mutagenic TLS,
whereas pol II and pol IV appear to be more specialized TLS polymerases.
PMID- 26442829
TI - Lower tacrolimus trough levels are associated with subsequently higher acute
rejection risk during the first 12 months after kidney transplantation.
AB - The premise that lower TAC trough levels are associated with subsequently higher
first BPAR risk during the first 12 mo post-transplant was recently questioned.
Using our prospectively followed cohort of 528 adult, primary kidney transplant
recipients (pooled across four randomized trials) who received reduced TAC dosing
plus an IMPDH inhibitor, TAC trough levels measured at seven time points, 7, 14
days, 1, 2, 3, 6 and 9 months post-transplant, were utilized along with Cox's
model to determine the multivariable significance of TAC level(t) (a continuous
time-dependent covariate equaling the most recently measured TAC level prior to
time t) on the hazard rate of developing first BPAR during the first 12 months
post-transplant. The percentage developing BPAR during the first 12 months post
transplant was 10.2% (54/528). In univariable analysis, lower TAC level(t) was
associated with a significantly higher BPAR rate (P = 0.00006), and its
significance was maintained even after controlling for 2 significant baseline
predictors (African-American/Hispanic Recipient and Developed DGF) in Cox's model
(multivariable P = 0.0003). Use of a cutpoint, TAC level(t) <4.0 vs. >=4.0 ng/ml,
yielded an even greater association with BPAR rate (univariable and multivariable
P < 0.000001), with an estimated hazard ratio of 6.33. These results suggest that
TAC levels <4.0 ng/ml should be avoided during the first 12 months post
transplant when TAC is used in combination with fixed-dose mycophenolate with or
without corticosteroids and induction therapy.
PMID- 26442827
TI - DNA Mismatch Repair.
AB - DNA mismatch repair (MMR) corrects replication errors in newly synthesized DNA.
It also has an antirecombination action on heteroduplexes that contain similar
but not identical sequences. This review focuses on the genetics and development
of MMR and not on the latest biochemical mechanisms. The main focus is on MMR in
Escherichia coli, but examples from Streptococcuspneumoniae and Bacillussubtilis
have also been included. In most organisms, only MutS (detects mismatches) and
MutL (an endonuclease) and a single exonucleaseare present. How this system
discriminates between newlysynthesized and parental DNA strands is not clear. In
E. coli and its relatives, however, Dam methylation is an integral part of MMR
and is the basis for strand discrimination. A dedicated site-specific
endonuclease, MutH, is present, andMutL has no endonuclease activity; four
exonucleases can participate in MMR. Although it might seem that the accumulated
wealth of genetic and biochemical data has given us a detailed picture of the
mechanism of MMR in E. coli, the existence of three competing models to explain
the initiation phase indicates the complexity of the system. The mechanism of the
antirecombination action of MMR is largely unknown, but only MutS and MutL appear
to be necessary. A primary site of action appears to be on RecA, although
subsequent steps of the recombination process can also be inhibited. In this
review, the genetics of Very Short Patch (VSP) repair of T/G mismatches arising
from deamination of 5-methylcytosineresidues is also discussed.
PMID- 26442830
TI - Simulating photoacoustic waves produced by individual biological particles with
spheroidal wave functions.
AB - Under the usual approximation of treating a biological particle as a spheroidal
droplet, we consider the analysis of its size and shape with the high frequency
photoacoustics and develop a numerical method which can simulate its
characteristic photoacoustic waves. This numerical method is based on the
calculation of spheroidal wave functions, and when comparing to the finite
element model (FEM) calculation, can reveal more physical information and can
provide results independently at each spatial points. As the demonstration, red
blood cells (RBCs) and MCF7 cell nuclei are studied, and their photoacoustic
responses including field distribution, spectral amplitude, and pulse forming are
calculated. We expect that integrating this numerical method with the high
frequency photoacoustic measurement will form a new modality being extra to the
light scattering method, for fast assessing the morphology of a biological
particle.
PMID- 26442831
TI - Interaction mechanism exploration of R-bicalutamide/S-1 with WT/W741L AR using
molecular dynamics simulations.
AB - R-Bicalutamide is a first generation antiandrogen used to treat prostate cancer,
which inhibits androgen action by competitively binding to the androgen receptor
(AR). However, R-bicalutamide was discovered to exhibit some agonistic properties
in clinical application. According to reports, the W741L AR mutation may lead to
resistance towards R-bicalutamide. But the mechanism of the R-bicalutamide switch
from an antagonist to an agonist due to the mutation of AR W741L is still not so
clear. Another molecule, S-1, owing to a very similar structure to R
bicalutamide, is always agonistic to both the wild type and W741L AR. The main
difference between these two chemicals is that S-1 has an ether linkage while R
bicalutamide has a sulfonyl group. To study the drug-resistant mechanism caused
by W741L mutation and the opposite effects arising from subtle structure
differences, molecular dynamics (MD) simulations and molecular mechanics
generalized Born surface area (MM-GBSA) calculations were employed to explore the
interaction mechanisms between R-bicalutamide/S-1 and WT/W741L AR. The calculated
binding free energies are in accordance with the reported experimental values.
The obtained results indicate that M895 and W741 are vital amino acids in the
antagonism of R-bicalutamide. The bulkier substitution of sulfonyl and tryptophan
push aside M895, together with helix 12 (H12), to expose the ligand-binding
domain resulting in the antagonistic conformation of the AR. If W741 is mutated
to L741, the B-ring of these two chemicals would shift toward L741. At the same
time, M895 dragging helix H12, would also move closer to L741. So H12 tends to
cover the AR ligand-binding domain to a certain degree, changing the androgen
receptor from an antagonistic to an agonistic conformation, which may explain the
agonism of R-bicalutamide to the mutant W741L AR.
PMID- 26442832
TI - Decreased expression of pSTAT, IRF-1 and DAP10 signalling molecules in peripheral
blood lymphocytes of patients with metastatic melanoma.
AB - AIMS: As numerous signalling molecules regulate effector functions of peripheral
blood lymphocytes (PBLs) that have an important anti-tumour activity, the aim of
this study was to analyse their level in patients with metastatic melanoma (MM)
compared with healthy controls (HCs). METHODS: Peripheral blood mononuclear cells
(PBMCs) of 36 MMs and 28 HCs were analysed for the level of perforin, interferon
regulating transcription factor-1 (IRF-1), DAP10 and Src homology 2 domain
containing tyrosine phosphatase-1 by reverse transcriptase PCR, level of
phosphorylated signal transducers and activators of transcription (pSTAT)-1,
pSTAT-4, pSTAT-5 by western blot and interferon (IFN)-gamma production by ELISA.
The expression of activating NKG2D and inhibitory killer immunoglobulin-like
receptors (KIR), CD158a and CD158b, on PBL, CD3-CD56+ natural killer (NK) cells
and CD3+CD8+ cytotoxic T lymphocytes (CTLs), as well as the percentage of
CD14+HLA-DR- cells in PBMC were estimated by flow cytometry. RESULTS: Patients
with MM, compared with HCs, had significantly lower level of cytotoxic molecule
perforin and decreased IFN-gamma production, as well as lower level of pSTAT-1,
pSTAT-4, pSTAT-5 and IRF-1 signalling molecules in PBMC. Furthermore, MM had
decreased expression of activating NKG2D receptor on PBL and NK cells and low
level of its DAP10 signalling molecule contrary to no changes in KIR expression
on all investigated cells. These results could be associated with increased
percentage of immunosuppressive CD14+HLA-DR- myeloid-derived suppressor cells
detected in patients with MM. CONCLUSIONS: The altered signalling molecules of
PBL could represent biomarkers of impaired cytotoxic and immunoregulatory
function of these cells, indicating melanoma-associated immunosuppression that
facilitates tumour progression.
PMID- 26442828
TI - Stress-Induced Mutagenesis.
AB - Early research on the origins and mechanisms of mutation led to the establishment
of the dogma that, in the absence of external forces, spontaneous mutation rates
are constant. However, recent results from a variety of experimental systems
suggest that mutation rates can increase in response to selective pressures. This
chapter summarizes data demonstrating that,under stressful conditions,
Escherichia coli and Salmonella can increase the likelihood of beneficial
mutations by modulating their potential for genetic change.Several experimental
systems used to study stress-induced mutagenesis are discussed, with special
emphasison the Foster-Cairns system for "adaptive mutation" in E. coli and
Salmonella. Examples from other model systems are given to illustrate that stress
induced mutagenesis is a natural and general phenomenon that is not confined to
enteric bacteria. Finally, some of the controversy in the field of stress-induced
mutagenesis is summarized and discussed, and a perspective on the current state
of the field is provided.
PMID- 26442834
TI - [Ezetimibe in clinical practice: from laboratory investigations to the IMPROVE-IT
trial results].
AB - The impact of low density lipoprotein (LDL) cholesterol levels on cardiovascular
risk has been extensively studied. Statins have been demonstrated to
significantly reduce LDL cholesterol levels, contributing to cardiovascular risk
reduction particularly in patients with high cardiovascular risk. However, low
adherence to statin therapy, often due to adverse effects, has raised the need
for new pharmacological approaches to combine with statin therapy in order to
reach the target levels of LDL cholesterol. Ezetimibe is a selective inhibitor of
Niemann-Pick C1-like 1 (NPC1L1) protein that regulates the cholesterol uptake
from the small intestine into the enterocytes. Ezetimibe has been demonstrated to
significantly reduce LDL cholesterol levels in combination with statins and
recent trials support its role in reducing the risk of cardiovascular events.
PMID- 26442833
TI - Prevention for Pediatric and Adolescent Migraine.
AB - Children and adolescents can experience significant disability from frequent
migraine. A number of tools have been developed to help quantify the impact of
migraine in this population. Many preventative medications used in adults are
routinely used to prevent migraines in children, although there has been less
rigorous study. This article reviews the indications and evidence for the use of
migraine preventatives, such as antidepressants, antihypertensives,
anticonvulsants, antihistamines, and botulinum toxin, in this population.
PMID- 26442835
TI - Adsorption of Anionic or Cationic Surfactants in Polyanionic Brushes and Its
Effect on Brush Swelling and Fouling Resistance during Emulsion Filtration.
AB - Atom transfer radical polymerization of ionic monomers from membrane surfaces
yields polyelectrolyte brushes that swell in water and repel oil droplets to
resist fouling during filtration of oil-in-water emulsions. However, surfactant
adsorption to polyelectrolyte brushes may overcome this fouling resistance. This
work examines adsorption of cationic and anionic surfactants in polyanionic
brushes and the effect of these surfactants on emulsion filtration. In situ
ellipsometry with films on flat surfaces shows that brushes composed of poly(3
sulfopropyl methacrylate salts) (pSPMK) swell 280% in water and do not adsorb
sodium dodecyl sulfate (SDS). pSPMK-modified microfiltration membranes reject
>99.9% of the oil from SDS-stabilized submicron emulsions, and the specific flux
through these modified membranes is comparable to that through NF270
nanofiltration membranes. Moreover, the brush-modified membranes show no decline
in flux over a 12 h filtration, whereas the flux through NF270 membranes
decreases by 98.7%. In contrast, pSPMK brushes adsorb large quantities of
cetyltrimethylammonium bromide (CTAB), and at low chain densities the brushes
collapse in the presence of this cationic surfactant. Filtration of CTAB
stabilized emulsions through pSPMK-modified membranes gives minimal oil
rejection, presumably due to the brush collapse. Thus, the fouling resistance of
polyelectrolyte brush-modified membranes clearly depends on the surfactant
composition in a particular emulsion.
PMID- 26442837
TI - The impact of occupational therapy and lifestyle interventions on older persons'
health, well-being, and occupational adaptation.
AB - AIM: The aim of this study was to investigate whether a four-month occupational
based health-promoting programme for older persons living in community dwellings
could maintain/improve their general health and well-being. Further, the aim was
to explore whether the programme facilitated the older persons' occupational
adaptation. METHODS: The study had a quasi-experimental design, with a non
equivalent control group combined with semi-structured interviews. The
intervention group comprised 22 participants, and the control group 18. Outcomes
were measured using the Short Form 36, Life Satisfaction Index-Z and Meaningful
Activity Participation Assessment. Content analysis, based on concepts from the
Model of Occupational Adaptation, was used to analyse the interviews. RESULTS:
The intervention group showed statistically significant improvements in general
health variables such as vitality and mental health, and positive trends for
psychological well-being. There were no statistically significant differences
between the intervention group and the control group, but the groups were not
fully matched. The qualitative analysis based on Occupational Adaptation pointed
out social aspects as a compliment to the overall results. CONCLUSIONS:
Participating in meaningful, challenging activities in different environments
stimulates the occupational adaptation process; this is something occupational
therapists could use to empower older persons to find their optimal occupational
lives.
PMID- 26442836
TI - A genetic risk score comprising known venous thromboembolism loci is associated
with chronic venous disease in a multi-ethnic cohort.
AB - BACKGROUND: Chronic venous disease is common and shares some risk factors with
venous thromboembolism (VTE). Several genetic loci have been discovered and well
replicated for VTE in European descent populations. We examined associations of a
genetic risk score (GRS), comprising known VTE loci, with chronic venous disease.
METHODS: The San Diego Population Study (SDPS) is a multi-ethnic cohort that
evaluated 2404 men and women aged 29-91 from 1994 to 1998 for chronic venous
disease. The current study includes 1447 participants genotyped for 33 variants
in 22 established VTE risk loci. Using these variants, unweighted and weighted
GRS were constructed. Logistic regression was used to examine associations with
venous disease. RESULTS: In non-Hispanic whites, African-Americans, Hispanics,
and Asians, each standard deviation increment higher of the unweighted 33-SNP GRS
was associated with a 1.45-fold (95% CI (1.26, 1.67)), 1.74-fold (1.18, 2.55), a
1.80-fold (1.30, 2.51), and 1.88-fold (1.30, 2.73) greater odds, respectively,
for moderate plus severe disease. The difference in c-statistics was significant
between a known venous risk factor model and a model adding the 33-SNP GRS for
whites (p=0.008), African-Americans (0.03), and Hispanics (p=0.04), with marginal
significance in Asians (p=0.06). CONCLUSIONS: GRS comprising variants primarily
from VTE findings in European descent populations were associated with chronic
venous disease across all race/ethnic groups, and contributed significantly to
prediction, indicating some level of generalizability to other race/ethnic
groups. Future work should focus on more in depth examination of racial/ethnic
group genetic architecture in relation to chronic venous disease.
PMID- 26442838
TI - Relative sensitivities among avian species to individual and mixtures of aryl
hydrocarbon receptor-active compounds.
AB - Dioxins and dioxin-like compounds (DLCs) are potent toxicants to most
vertebrates. Sensitivities to DLCs vary among species. In the present study, the
sensitivities of avian species (chicken [Gallus gallus], ring-necked pheasant
[Phasianus colchicus], and Japanese quail [Coturnix japonica]) to some
polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs)
were determined by using species-specific, in vitro, transactivation assays based
on a luciferase reporter gene under control of species-specific aryl hydrocarbon
receptors. In ring-necked pheasant and Japanese quail, 2,3,7,8-tetrachlorodibenzo
p-dioxin (TCDD) was not the most potent inducer of toxic effects. Especially for
Japanese quail, the relative potency values of most of 9 PCDD/Fs tested were
greater than for TCDD. The rank order of avian species sensitivities to DLCs was
chicken > ring-necked pheasant > Japanese quail. Effects of binary mixtures of
TCDD, 2,3,7,8-tetrachlorodibenzofuran, and 2,3,4,7,8-pentachlorodibenzofuran were
strictly additive. Moreover, we also found that the primary DLCs that were
responsible for most of the potency of the DLC mixtures can be deduced by using
ordination in a multidimensional space defined by the avian species
sensitivities. Overall, the relative potency and the species sensitivities of
these chemicals could guide risk assessments to wild species when exposure to
mixtures of DLCs in the environment.
PMID- 26442839
TI - Marinobacter confluentis sp. nov., a lipolytic bacterium isolated from a junction
between the ocean and a freshwater lake.
AB - A Gram-stain-negative, motile, aerobic and rod-shaped bacterium, designated HJM
18T, was isolated from the place where the ocean and a freshwater lake meet at
Hwajinpo, South Korea, and subjected to a taxonomic study using a polyphasic
approach. Strain HJM-18T grew optimally at 30 degrees C, at pH 7.0-8.0 and in
the presence of 1.0-3.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene
sequences showed that strain HJM-18T belonged to the genus Marinobacter. Strain
HJM-18T exhibited 16S rRNA gene sequence similarity values of 97.05-98.22 % to
the type strains of Marinobacter algicola, Marinobacter flavimaris, Marinobacter
adhaerens, Marinobacter salarius, Marinobacter salsuginis, Marinobacter guineae
and Marinobacter gudaonensis and of 93.21-96.98 % to the type strains of the
other species of the genus Marinobacter. Strain HJM-18T contained Q-9 as the
predominant ubiquinone and summed feature 3 (C16 : 1omega7c and/or C16 :
1omega6c), C16 : 0 and C18 : 1omega9c as the major fatty acids. The major polar
lipids detected in strain HJM-18T were phosphatidylethanolamine,
phosphatidylglycerol and one unidentified aminophospholipid. The DNA G+C content
was 58 mol% and the mean DNA-DNA relatedness values with the type strains of the
seven phylogenetically related species of the genus Marinobacter were 10-27 %.
Differential phenotypic properties, together with phylogenetic and genetic
distinctiveness, revealed that strain HJM-18T is separated from recognized
species of the genus Marinobacter. On the basis of the data presented, strain HJM
18T represents a novel species of the genus Marinobacter, for which the name
Marinobacter confluentis sp. nov. is proposed. The type strain is HJM-18T ( =
KCTC 42705T = NBRC 111223T).
PMID- 26442840
TI - Cyclization of sulfide, ether or tertiary amine-tethered N-sulfonyl-1,2,3
triazoles: a facile synthetic protocol for 3-substituted isoquinolines or
dihydroisoquinolines.
AB - A facile synthetic method to access 3-substituted isoquinoline or
dihydroisoquinoline derivatives has been developed via a novel cyclization
reaction of N-sulfonyl-1,2,3-triazole derivatives by thermally induced
rearrangement.
PMID- 26442842
TI - Response to 'Effect of metabolic components on incident type 2 diabetes mellitus
in nonalcoholic fatty liver disease subjects'.
PMID- 26442841
TI - Diversity Matters: A Revised Guide to Myelination.
AB - The evolutionary success of the vertebrate nervous system is largely due to a
unique structural feature--the myelin sheath, a fatty envelope that surrounds the
axons of neurons. By increasing the speed by which electrical signals travel
along axons, myelin facilitates neuronal communication between distant regions of
the nervous system. We review the cellular and molecular mechanisms that regulate
the development of myelin as well as its homeostasis in adulthood. We discuss how
finely tuned neuron-oligodendrocyte interactions are central to myelin formation
during development and in the adult, and how these interactions can have profound
implications for the plasticity of the adult brain. We also speculate how the
functional diversity of both neurons and oligodendrocytes may impact on the
myelination process in both health and disease.
PMID- 26442843
TI - The History of Patenting Genetic Material.
AB - The US Supreme Court's recent decision in Association for Molecular Pathology v.
Myriad Genetics, Inc. declared, for the first time, that isolated human genes
cannot be patented. Many have wondered how genes were ever the subjects of
patents. The answer lies in a nuanced understanding of both legal and scientific
history. Since the early twentieth century, "products of nature" were not
eligible to be patented unless they were "isolated and purified" from their
surrounding environment. As molecular biology advanced, and the capability to
isolate genes both physically and by sequence came to fruition, researchers (and
patent offices) began to apply patent-law logic to genes themselves. These
patents, along with other biological patents, generated substantial social and
political criticism. Myriad Genetics, a company with patents on BRCA1 and BRCA2,
two genes critical to assessing early-onset breast and ovarian cancer risk, and
with a particularly controversial business approach, became the antagonist in an
ultimately successful campaign to overturn gene patents in court. Despite
Myriad's defeat, some questions concerning the rights to monopolize genetic
information remain. The history leading to that defeat may be relevant to these
future issues.
PMID- 26442844
TI - General Stress Signaling in the Alphaproteobacteria.
AB - The Alphaproteobacteria uniquely integrate features of two-component signal
transduction and alternative sigma factor regulation to control transcription of
genes that ensure growth and survival across a range of stress conditions.
Research over the past decade has led to the discovery of the key molecular
players of this general stress response (GSR) system, including the sigma factor
sigma(EcfG), its anti-sigma factor NepR, and the anti-anti-sigma factor PhyR. The
central molecular event of GSR activation entails aspartyl phosphorylation of
PhyR, which promotes its binding to NepR and thereby releases sigma(EcfG) to
associate with RNAP and direct transcription. Recent studies are providing a new
understanding of complex, multilayered sensory networks that activate and repress
this central protein partner switch. This review synthesizes our structural and
functional understanding of the core GSR regulatory proteins and highlights
emerging data that are defining the systems that regulate GSR transcription in a
variety of species.
PMID- 26442845
TI - Understanding Language from a Genomic Perspective.
AB - Language is a defining characteristic of the human species, but its foundations
remain mysterious. Heritable disorders offer a gateway into biological
underpinnings, as illustrated by the discovery that FOXP2 disruptions cause a
rare form of speech and language impairment. The genetic architecture underlying
language-related disorders is complex, and although some progress has been made,
it has proved challenging to pinpoint additional relevant genes with confidence.
Next-generation sequencing and genome-wide association studies are
revolutionizing understanding of the genetic bases of other neurodevelopmental
disorders, like autism and schizophrenia, and providing fundamental insights into
the molecular networks crucial for typical brain development. We discuss how a
similar genomic perspective, brought to the investigation of language-related
phenotypes, promises to yield equally informative discoveries. Moreover, we
outline how follow-up studies of genetic findings using cellular systems and
animal models can help to elucidate the biological mechanisms involved in the
development of brain circuits supporting language.
PMID- 26442847
TI - The Biology and Evolution of Mammalian Y Chromosomes.
AB - Mammals have the oldest sex chromosome system known: the mammalian X and Y
chromosomes evolved from ordinary autosomes beginning at least 180 million years
ago. Despite their shared ancestry, mammalian Y chromosomes display enormous
variation among species in size, gene content, and structural complexity. Several
unique features of the Y chromosome--its lack of a homologous partner for
crossing over, its functional specialization for spermatogenesis, and its high
degree of sequence amplification--contribute to this extreme variation. However,
amid this evolutionary turmoil many commonalities have been revealed that have
contributed to our understanding of the selective pressures driving the evolution
and biology of the Y chromosome. Two biological themes have defined Y-chromosome
research over the past six decades: testis determination and spermatogenesis. A
third biological theme begins to emerge from recent insights into the Y
chromosome's roles beyond the reproductive tract--a theme that promises to
broaden the reach of Y-chromosome research by shedding light on fundamental sex
differences in human health and disease.
PMID- 26442848
TI - Chromothripsis: A New Mechanism for Rapid Karyotype Evolution.
AB - Chromosomal rearrangements are generally thought to accumulate gradually over
many generations. However, DNA sequencing of cancer and congenital disorders
uncovered a new pattern in which multiple rearrangements arise all at once. The
most striking example, chromothripsis, is characterized by tens or hundreds of
rearrangements confined to a single chromosome or to local regions over a few
chromosomes. Genomic analysis of chromothripsis and the search for its biological
mechanism have led to new insights on how chromosome segregation errors can
generate mutagenesis and changes to the karyotype. Here, we review the genomic
features of chromothripsis and summarize recent progress on understanding its
mechanism. This includes reviewing new work indicating that one mechanism to
generate chromothripsis is through the physical isolation of chromosomes in
abnormal nuclear structures (micronuclei). We also discuss connections revealed
by recent genomic analysis of cancers between chromothripsis, chromosome bridges,
and ring chromosomes.
PMID- 26442846
TI - Giving Time Purpose: The Synechococcus elongatus Clock in a Broader Network
Context.
AB - Early research on the cyanobacterial clock focused on characterizing the genes
needed to keep, entrain, and convey time within the cell. As the scope of assays
used in molecular genetics has expanded to capture systems-level properties
(e.g., RNA-seq, ChIP-seq, metabolomics, high-throughput screening of genetic
variants), so has our understanding of how the clock fits within and influences a
broader cellular context. Here we review the work that has established a global
perspective of the clock, with a focus on (a) an emerging network-centric view of
clock architecture, (b) mechanistic insights into how temporal and environmental
cues are transmitted and integrated within this network,
PMID- 26442849
TI - Asymmetry of the Brain: Development and Implications.
AB - Although the left and right hemispheres of our brains develop with a high degree
of symmetry at both the anatomical and functional levels, it has become clear
that subtle structural differences exist between the two sides and that each is
dominant in processing specific cognitive tasks. As the result of evolutionary
conservation or convergence, lateralization of the brain is found in both
vertebrates and invertebrates, suggesting that it provides significant fitness
for animal life. This widespread feature of hemispheric specialization has
allowed the emergence of model systems to study its development and, in some
cases, to link anatomical asymmetries to brain function and behavior. Here, we
present some of what is known about brain asymmetry in humans and model organisms
as well as what is known about the impact of environmental and genetic factors on
brain asymmetry development. We specifically highlight the progress made in
understanding the development of epithalamic asymmetries in zebrafish and how
this model provides an exciting opportunity to address brain asymmetry at
different levels of complexity.
PMID- 26442850
TI - Sarcoid-like reactions (SLRs) or autonomous sarcoidosis (AS)? Differentiation
probably important?
PMID- 26442851
TI - [Diagnostics and management of food allergies in childhood and adolescence].
AB - Food allergies can result in life-threatening reactions and diminish quality of
life. The prevalence of food allergies is increasing with large regional
variability. A few food allergens cover the majority of food-related reactions
(cow's milk, egg, wheat, soy, fish, crustacean, nuts and peanut). Food reactions
can be categorized in IgE-mediated and non-IgE-mediated, the latter of which
remaining often a clue in the diagnosis. Treatment of food allergy involves
mainly strict avoidance of the trigger food. Medications help to manage symptoms
of disease, but currently, there is no cure for food allergy.
PMID- 26442852
TI - Glial Fibrillary Acidic Protein-Expressing Glia in the Mouse Lung.
AB - Autonomic nerves regulate important functions in visceral organs, including the
lung. The postganglionic portion of these nerves is ensheathed by glial cells
known as non-myelinating Schwann cells. In the brain, glia play important
functional roles in neurotransmission, neuroinflammation, and maintenance of the
blood brain barrier. Similarly, enteric glia are now known to have analogous
roles in gastrointestinal neurotransmission, inflammatory response, and barrier
formation. In contrast to this, very little is known about the function of glia
in other visceral organs. Like the gut, the lung forms a barrier between airborne
pathogens and the bloodstream, and autonomic lung innervation is known to affect
pulmonary inflammation and lung function. Lung glia are described as non
myelinating Schwann cells but their function is not known, and indeed no
transgenic tools have been validated to study them in vivo. The primary goal of
this research was, therefore, to investigate the relationship between non
myelinating Schwann cells and pulmonary nerves in the airways and vasculature and
to validate existing transgenic mouse tools that would be useful for studying
their function. We focused on the glial fibrillary acidic protein promoter, which
is a cognate marker of astrocytes that is expressed by enteric glia and non
myelinating Schwann cells. We describe the morphology of non-myelinating Schwann
cells in the lung and verify that they express glial fibrillary acidic protein
and S100, a classic glial marker. Furthermore, we characterize the relationship
of non-myelinating Schwann cells to pulmonary nerves. Finally, we report tools
for studying their function, including a commercially available transgenic mouse
line.
PMID- 26442853
TI - Crosstalk Between MAPK/ERK and PI3K/AKT Signal Pathways During Brain
Ischemia/Reperfusion.
AB - The epidermal growth factor receptor (EGFR) is linked to the phosphatidylinositol
3-kinase (PI3K)/protein kinase B (AKT) and Raf/mitogen-activated protein kinase
(MAPK)/extracellular signal-regulated kinase (ERK1/2) signaling pathways. During
brain ischemia/reperfusion, EGFR could be transactivated, which stimulates these
intracellular signaling cascades that either protect cells or potentiate cell
injury. In the present study, we investigated the activation of EGFR, PI3K/AKT,
and Raf/MAPK/ERK1/2 during ischemia or reperfusion of the brain using the middle
cerebral artery occlusion model. We found that EGFR was phosphorylated and
transactivated during both ischemia and reperfusion periods. During ischemia, the
activity of PI3K/AKT pathway was significantly increased, as judged from the
strong phosphorylation of AKT; this activation was suppressed by the inhibitors
of EGFR and Zn-dependent metalloproteinase. Ischemia, however, did not induce
ERK1/2 phosphorylation, which was dependent on reperfusion. Coimmunoprecipitation
of Son of sevenless 1 (SOS1) with EGFR showed increased association between the
receptor and SOS1 in ischemia, indicating the inhibitory node downstream of SOS1.
The inhibitory phosphorylation site of Raf-1 at Ser259, but not its stimulatory
phosphorylation site at Ser338, was phosphorylated during ischemia. Furthermore,
ischemia prompted the interaction between Raf-1 and AKT, while both the
inhibitors of PI3K and AKT not only abolished AKT phosphorylation but also
restored ERK1/2 phosphorylation. All these findings suggest that Raf/MAPK/ERK1/2
signal pathway is inhibited by AKT via direct phosphorylation and inhibition at
Raf-1 node during ischemia. During reperfusion, we observed a significant
increase of ERK1/2 phosphorylation but no change in AKT phosphorylation.
Inhibitors of reactive oxygen species and phosphatase and tensin homolog restored
AKT phosphorylation but abolished ERK1/2 phosphorylation, suggesting that the
reactive oxygen species-dependent increase in phosphatase and tensin homolog
activity in reperfusion period relieves ERK1/2 from inhibition of AKT.
PMID- 26442855
TI - Microbiota-Gut-Brain Axis: Yeast Species Isolated from Stool Samples of Children
with Suspected or Diagnosed Autism Spectrum Disorders and In Vitro Susceptibility
Against Nystatin and Fluconazole.
AB - Autism spectrum disorder (ASD) is a general term for a group of complex
neurodevelopmental disorders of brain development that limits a person's ability
to function normally. Etiology has not been clearly defined up to date. However,
gut microbiota and the bidirectional communication between the gastrointestinal
tract and brain, the so-called microbiota-gut-brain axis, are hypothesized, which
may be involved in the etiology of several mental disorders. Recent reports
suggest that Candida, particularly Candida albicans, growth in intestines may
cause lower absorption of carbohydrates and minerals and higher toxin levels
which are thought to contribute autistic behaviors. The aim of this study was to
identify the 3-year deposited yeasts isolated from stool samples of children with
diagnosed or suspected ASD and to determine in vitro activity of nystatin and
fluconazole against these isolates using Clinical Laboratory Standards Institute
M27-A3 guidelines. A 17-year retrospective assessment was also done using our
laboratory records. Among the species identified, intrinsically fluconazole
resistant Candida krusei (19.8 %) and Candida glabrata (14.8 %) with elevated
MICs were remarkable. Overall, C. albicans (57.4 %) was the most commonly
isolated species in 17 years. The species identification and/or antifungal
susceptibility tests have to be performed using the strain isolated from stool
sample, to select the appropriate antifungal agent, if antimycotic therapy is
needed.
PMID- 26442854
TI - A case of oral mycosis fungoides successfully treated by combination of
alemtuzumab and chemotherapy.
PMID- 26442856
TI - Epithelial-Mesenchymal Transition Protein Expression in Basal Cell Adenomas and
Basal Cell Adenocarcinomas.
AB - Basal cell adenomas and basal cell adenocarcinomas show marked histomorphologic
similarity and are separated microscopically primarily by the invasive
characteristics of the adenocarcinomas. We wished to explore potential
differences in the expression of epithelial-mesenchymal transition associated
proteins in these two tumor types. A tissue microarray was constructed utilizing
29 basal cell adenomas and 16 basal cell adenocarcinomas. Immunohistochemical
expression of E-cadherin, beta-catenin, Twist 1 and vimentin were investigated.
Both tumors expressed all proteins in a relatively similar manner. Nuclear beta
catenin was essentially limited to the abluminal cell populations in both tumor
types. E-cadherin was limited largely to luminal locations but was more prevalent
in the adenocarcinomas as compared to the adenomas. Primarily abluminal
expression for vimentin was seen, sometimes present in an apical dot-like
pattern. Distinct populations of cellular expression of these four markers of
epithelial mesenchymal transition were present but were similar in locations in
both tumors with no patterns discerned to separate basal cell adenoma from basal
cell adenocarcinoma. Given these findings, the mechanisms by which basal cell
adenocarcinoma is able to invade while its counterpart, basal cell adenoma can
not, may be more complex than in other tumor types.
PMID- 26442857
TI - Tolerability of Antihypertensive Medications in Older Adults.
AB - Several guidelines for hypertension have recently undergone revisions to
incorporate an approach providing choices of medications based on age, race, and
specific situations where hypertension may co-exist with disorders such as
diabetes, coronary artery disease, heart failure and chronic kidney disease.
Initial recommendations include diuretics, angiotensin-converting enzyme
inhibitors, angiotensin receptor blockers, and calcium channel blockers; beta
blockers are favored in some guidelines and are a choice in specific settings.
Within the classes of drugs, several antihypertensive agents provide options.
This review discusses antihypertensive drugs by class, including adverse effects
and tolerability, with preferences in older adults and specific settings. Adverse
drug events from antihypertensive medications are discussed by class and where
applicable for specific agents. Data from select studies pertinent to
tolerability and adverse effects are presented in tables for several classes of
drugs. The rationale for nonadherence to medication is reviewed, including the
roles played by tolerability and adverse drug effects. Antihypertensive therapy
in typical settings in older adults is discussed; they include hypertension in
association with impaired cognition, depression, diabetes, sexual dysfunction,
and falls. The key to successful therapy and tolerability is to promote a healthy
lifestyle in conjunction with medications as the approach, thereby also lowering
the adverse drug effects. The eventual choice of the specific drug(s) is based on
risks, benefits, and patient preferences, and is best tailored for each older
adult.
PMID- 26442858
TI - Treatment of Exudative Age-related Macular Degeneration: Focus on Aflibercept.
AB - A formulation of aflibercept for intravitreal injection (Eylea) is approved for
the treatment of patients with exudative age-related macular degeneration (AMD).
Aflibercept has a significantly higher affinity for Vascular endothelial growth
factor (VEGF)-A compared with other monoclonal anti-VEGF antibodies. In addition
to binding all VEGF-A isoforms, aflibercept also blocks other proangiogenic
factors such as VEGF-B and placental growth factor. The VIEW 1 and 2 trials
showed this drug achieves improved results in patients with exudative AMD similar
to those obtained with monthly ranibizumab, using a bimonthly treatment regimen
after a loading dose of three intravitreal injections, which translates to less
use of healthcare resources. There is a subgroup of patients that present with
persistent fluid after the loading dose that could benefit from monthly
injections or personalized proactive treatment after the first year. In the
second year of treatment, the Treat and Extend patterns can permit even more
lengthening of the time between injections. More data are needed to confirm the
optimal monitoring and retreatment dosing, to maintain long-term efficacy. Other
preliminary data suggest that patients that do not respond to other anti
angiogenics and patients with special pathologies such as polypoidal
choroidopathy or retinal angiomatous proliferation can improve upon switching to
aflibercept. To date, the safety profile of aflibercept is excellent and is
comparable to other anti-angiogenic treatments.
PMID- 26442860
TI - Immunogenicity and Safety of Intradermal Influenza Vaccine in the Elderly: A Meta
Analysis of Randomized Controlled Trials.
AB - INTRODUCTION: Immunosenescence makes the elderly more susceptible to influenza
complications and less responsive to vaccination. An intradermal formulation
(IDflu) is one of several strategies being investigated to increase the
immunogenicity of influenza vaccines. OBJECTIVE: The overall goal of the study
was to assess the safety and immunogenicity of IDflu compared with the
intramuscular route (IMflu) in the elderly. METHODS: A meta-analysis of
randomized controlled trials (RCTs) was performed. Included articles met the
following criteria: RCTs; primary studies, not re-analyses or reviews; enrolment
of elderly people; comparing the immunogenicity and/or safety of IDflu with
IMflu; measuring seroprotection and/or seroconversion rate to assess
immunogenicity; measuring local reactions and/or general symptoms and/or other
mild local reactions that could affect acceptability of vaccine as safety
indicators, according to the European Medicines Agency (EMA) criteria; published
through January 2015. RESULTS: The results of our meta-analysis on seroprotection
showed that IDflu is comparable to IMflu for each strain (A/H1N1: risk ratio [RR]
1.02, 95% confidence interval [CI] 0.98-1.07; A/H3N2: RR 1.01, 95% CI 0.99-1.04;
B 1.02, 95% CI 0.98-1.08). The seroconversion rate achieved with IDflu was
comparable to that of the control group (A/H1N1: RR 1.08, 95% CI 0.97-1.2;
A/H3N2: RR 1.08, 95% CI 0.96-1.21; B: RR 1.21, 95% CI 1-1.45). Systemic
reactogenicity appeared similar in the two groups, while local reactions were
significantly more frequent in the IDflu group. CONCLUSIONS: The novel IDflu
appears to have the adequate balance between immunogenicity and safety in the
elderly compared with IMflu, and its utilization may be considered among the
possible strategies to enhance the control of seasonal influenza outbreaks
according to the existing policy recommendations in the elderly.
PMID- 26442859
TI - Novel Therapies for Metastatic Melanoma: An Update on Their Use in Older
Patients.
AB - Cutaneous melanoma is the most aggressive form of skin cancer. With age as a risk
factor, melanoma is projected to become a substantial healthcare burden. The
clinical course of melanoma in older patients is different from that in middle
aged and younger patients: melanomas are thicker, have higher mitotic rates and
are more likely to be ulcerated. Older patients also have a higher mortality
rate, yet, paradoxically, have a lower rate of lymph node metastases. After
decades of no significant progress in the treatment of this devastating disease,
novel insights into the mechanisms underlying the pathophysiology of metastatic
melanoma have led to new and remarkably efficient therapeutic opportunities. The
discovery that about half of all melanomas carry BRAF mutations led to the
introduction of targeted therapy with significant improvements in clinical
outcomes. Although these drugs appear to be equally effective in older patients,
specific considerations regarding adverse events are required. Besides targeted
therapy, immunotherapy has emerged as an alternative therapeutic option.
Antibodies that block cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed
cell death protein 1 (PD-1) can induce responses with high durability. Despite an
aging immune system, older patients seem to benefit to the same degree from these
treatments, apparently without increased toxicity. In this review, we focus on
the epidemiology, clinicopathological features, and recent developments of
systemic treatment in cutaneous melanoma with regard to older patients.
PMID- 26442861
TI - Prevalence of Potential and Clinically Relevant Statin-Drug Interactions in Frail
and Robust Older Inpatients.
AB - BACKGROUND: A significant proportion of older people are prescribed statins and
are also exposed to polypharmacy, placing them at increased risk of statin-drug
interactions. OBJECTIVE: To describe the prevalence rates of potential and
clinically relevant statin-drug interactions in older inpatients according to
frailty status. METHODS: A cross-sectional study of patients aged >=65 years who
were prescribed a statin and were admitted to a teaching hospital between 30 July
and 10 October 2014 in Sydney, Australia, was conducted. Data on socio
demographics, comorbidities and medications were collected using a standardized
questionnaire. Potential statin-drug interactions were defined if listed in the
Australian Medicines Handbook and three international drug information sources:
the British National Formulary, Drug Interaction Facts and Drug-Reax((r)).
Clinically relevant statin-drug interactions were defined as interactions with
the highest severity rating in at least two of the three international drug
information sources. Frailty was assessed using the Reported Edmonton Frail
Scale. RESULTS: A total of 180 participants were recruited (median age 78 years,
interquartile range 14), 35.0% frail and 65.0% robust. Potential statin-drug
interactions were identified in 10% of participants, 12.7% of frail participants
and 8.5% of robust participants. Clinically relevant statin-drug interactions
were identified in 7.8% of participants, 9.5% of frail participants and 6.8% of
robust participants. Depending on the drug information source used, the
prevalence rates of potential and clinically relevant statin-drug interactions
ranged between 14.4 and 35.6% and between 14.4 and 20.6%, respectively.
CONCLUSION: In our study of frail and robust older inpatients taking statins, the
overall prevalence of potential statin-drug interactions was low and varied
significantly according to the drug information source used.
PMID- 26442862
TI - The Association Between Anticholinergic Medication Burden and Health Related
Outcomes in the 'Oldest Old': A Systematic Review of the Literature.
AB - BACKGROUND: Increased exposure to anticholinergic medication is problematic,
particularly in those aged 80 years and older. OBJECTIVE: The aim of this
systematic review was to identify tools used to quantify anticholinergic
medication burden and determine the most appropriate tool for use in longitudinal
research, conducted in those aged 80 years and older. METHODS: A systematic
literature search was conducted across six electronic databases to identify
existing tools. Data extraction was conducted independently by two researchers;
studies describing the development of each tool were also retrieved and relevant
data extracted. An assessment of quality was completed for all studies. Tools
were assessed in terms of their measurement of the association between
anticholinergic medication burden and a defined set of clinical outcomes, their
development and their suitability for use in longitudinal research; the latter
was evaluated on the basis of criteria defined as the key attributes of an ideal
anticholinergic risk tool. RESULTS: In total, 807 papers were retrieved, 13
studies were eligible for inclusion and eight tools were identified. Included
studies were classed as 'very good' or 'good' following the quality assessment
analysis; one study was unclassified. Anticholinergic medication burden as
measured in studies was associated with impaired cognitive and physical function,
as well as an increased frequency of falls. The Drug Burden Index (DBI) exhibited
most of the key attributes of an ideal anticholinergic risk tool. CONCLUSION:
This review identified the DBI as the most appropriate tool for use in
longitudinal research focused on older people and their exposure to
anticholinergic medication burden.
PMID- 26442863
TI - High-Dose Nicotinamide Suppresses ROS Generation and Augments Population
Expansion during CD8(+) T Cell Activation.
AB - During T cell activation, mitochondrial content increases to meet the high energy
demand of rapid cell proliferation. With this increase, the level of reactive
oxygen species (ROS) also increases and causes the rapid apoptotic death of
activated cells, thereby facilitating T cell homeostasis. Nicotinamide (NAM) has
previously been shown to enhance mitochondria quality and extend the replicative
life span of human fibroblasts. In this study, we examined the effect of NAM on
CD8(+) T cell activation. NAM treatment attenuated the increase of mitochondrial
content and ROS in T cells activated by CD3/CD28 antibodies. This was accompanied
by an accelerated and higher-level clonal expansion resulting from attenuated
apoptotic death but not increased division of the activated cells. Attenuation of
ROS-triggered pro-apoptotic events and upregulation of Bcl-2 expression appeared
to be involved. Although cells activated in the presence of NAM exhibited
compromised cytokine gene expression, our results suggest a means to augment the
size of T cell expansion during activation without consuming their limited
replicative potential.
PMID- 26442864
TI - NRROS Negatively Regulates Osteoclast Differentiation by Inhibiting RANKL
Mediated NF-N:B and Reactive Oxygen Species Pathways.
AB - Negative regulator of reactive oxygen species (NRROS) is known to repress ROS
generation in phagocytes. In this study, we examined the roles of NRROS in both
osteoclasts and osteoblasts. Our results demonstrate that NRROS negatively
regulates the differentiation of osteoclasts, but not osteoblasts. Further,
overexpression of NRROS in osteoclast precursor cells attenuates RANKL-induced
osteoclast differentiation. Conversely, osteoclast differentiation is enhanced
upon siRNA-mediated knockdown of NRROS. Additionally, NRROS attenuates RANKL
induced NF-N:B activation, as well as degradation of the NOX1 and NOX2 proteins,
which are required for ROS generation. Based on our observations, we present
NRROS as a novel negative regulator of RANKL-induced osteoclastogenesis.
PMID- 26442866
TI - Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting
Endoplasmic Reticulum (ER) Stress Induced by Disturbed Flow.
AB - Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant
atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it
was found that disturbed flow can directly induce endoplasmic reticulum (ER)
stress in ECs, thereby playing a critical role in the development and progression
of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid,
has long been used to treat chronic cholestatic liver disease and is known to
alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its
role in atherosclerosis remains unexplored. In this study, we demonstrated the
anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER
stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a
reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous
protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory
responses such as increases in adhesion molecules, monocyte adhesion to ECs, and
apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis,
UDCA inhibits atheromatous plaque formation through the alleviation of ER stress
and a decrease in adhesion molecules. Taken together, our results revealed that
UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis
by inhibiting ER stress and the inflammatory response. This study suggests that
UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.
PMID- 26442865
TI - PGC-Enriched miRNAs Control Germ Cell Development.
AB - Non-coding microRNAs (miRNAs) regulate the translation of target messenger RNAs
(mRNAs) involved in the growth and development of a variety of cells, including
primordial germ cells (PGCs) which play an essential role in germ cell
development. However, the target mRNAs and the regulatory networks influenced by
miRNAs in PGCs remain unclear. Here, we demonstrate a novel miRNAs control PGC
development through targeting mRNAs involved in various cellular pathways. We
reveal the PGC-enriched expression patterns of nine miRNAs, including miR-10b,
18a, -93, -106b, -126-3p, -127, -181a, -181b, and -301, using miRNA expression
analysis along with mRNA microarray analysis in PGCs, embryonic gonads, and
postnatal testes. These miRNAs are highly expressed in PGCs, as demonstrated by
Northern blotting, miRNA in situ hybridization assay, and miRNA qPCR analysis.
This integrative study utilizing mRNA microarray analysis and miRNA target
prediction demonstrates the regulatory networks through which these miRNAs
regulate their potential target genes during PGC development. The elucidated
networks of miRNAs disclose a coordinated molecular mechanism by which these
miRNAs regulate distinct cellular pathways in PGCs that determine germ cell
development.
PMID- 26442867
TI - Reversibly Switching Silver Hierarchical Structures via Reaction Kinetics.
AB - Here we report a study on controllable synthesis of hierarchical silver
structures via regulating reaction kinetics. Silver particles with various
morphologies are synthesized by a solution-based reduction approach at the
addition of amino acids. The amino acid is used to coordinate with silver ions to
slow down the reduction of silver ions. With the increase of glycine
concentration, the morphologies of silver particles switch from dendrites, to
flowers and to compacted spheres, which is attributed to the decrease of reaction
rate as a result of the coordination. Three more amino acids are examined and
confirms the role of reaction kinetic in shaping silver particles. Furthermore,
by increasing the concentration of the reductant, the silver morphologies change
from compact spheres to loose flowers as a result of the increase of reaction
rate. Therefore the silver hierarchical structure can be reversibly switched by
reaction kinetics. The silver particles synthesized are tested for surface
enhanced Raman scattering (SERS) property and the dendritic particles present a
remarkable SERS activity. This study shows that reaction kinetics is a powerful
tool to tune hierarchical structures of silver particles, which is expected to be
transferable to other material systems.
PMID- 26442868
TI - Australia needs more occupational therapists in rural mental health services.
PMID- 26442869
TI - Modernising occupational therapy teaching, research and practice in mental
health.
PMID- 26442870
TI - Re: Modernising occupational therapy teaching, research and practice in mental
health.
PMID- 26442871
TI - Occupational therapy intervention in mental health should be individualised,
occupation focussed, promote inclusion and occur in the context of an authentic
relationship.
PMID- 26442872
TI - Cognitive adaptation training demonstrated benefits for individuals living with
schizophrenia in terms of community functioning and impact of auditory
hallucinations.
PMID- 26442873
TI - Occupational Therapy Australia Scope of Practice Framework and Statement
resources: update.
PMID- 26442874
TI - Assessment of native plant species for phytoremediation of heavy metals growing
in the vicinity of NTPC sites, Kahalgaon, India.
AB - The present investigation was carried out to screen native plants growing in fly
ash (FA) contaminated areas near National Thermal Power Corporation (NTPC),
Kahalgaon, Bihar, India with a view to using them for the eco-restoration of the
area. A total number of 30 plant species (5 aquatic and 25 terrestrial including
6 ferns) were collected and their diversity status and dominance were also
studied. After screening of dominant species at highly polluted site, 8
terrestrial and 5 aquatic plants were analyzed for heavy metals (Fe, Zn, Cu, Ni,
Si, Al, Pb, Cr, and Cd). Differential accumulations of various heavy metals by
different species of plants were observed. Typha latifolia was found to be most
efficient metal accumulator of Fe (927), Cu (58), Zn (87), Ni (57), Al (67), Cd
(95), and Pb (69), and Azolla pinnata as Cr (93) hyper-accumulator among aquatic
species in ug g(-1). In terrestrial species the maximum levels of Fe (998), Zn
(81), Ni (93), Al (121), and Si (156) were found in Croton bonplandium. However,
there was high spatial variability in total metal accumulation in different
species indicated by coefficient of variation (CV%). These results suggest that
various aquatic, some dominant terrestrial plants including fern species may be
used in a synergistic way to remediate and restore the FA contaminated
wastelands.
PMID- 26442878
TI - A cross reactive sensor array to probe divalent metal ions.
AB - A simple sensing ensemble was designed to discriminate structurally similar
divalent metal chlorides utilizing multivariate data analysis. The system
features the binding of four synthesized coumarin-enamine probes to a series of
ten metal chlorides. Linear discriminant analysis (LDA) achieves what univariate
data analysis alone cannot i.e., full analyte discrimination and differentiation.
PMID- 26442875
TI - Homology-directed repair in rodent zygotes using Cas9 and TALEN engineered
proteins.
AB - The generation of genetically-modified organisms has been revolutionized by the
development of new genome editing technologies based on the use of gene-specific
nucleases, such as meganucleases, ZFNs, TALENs and CRISPRs-Cas9 systems. The most
rapid and cost-effective way to generate genetically-modified animals is by
microinjection of the nucleic acids encoding gene-specific nucleases into
zygotes. However, the efficiency of the procedure can still be improved. In this
work we aim to increase the efficiency of CRISPRs-Cas9 and TALENs homology
directed repair by using TALENs and Cas9 proteins, instead of mRNA, microinjected
into rat and mouse zygotes along with long or short donor DNAs. We observed that
Cas9 protein was more efficient at homology-directed repair than mRNA, while
TALEN protein was less efficient than mRNA at inducing homology-directed repair.
Our results indicate that the use of Cas9 protein could represent a simple and
practical methodological alternative to Cas9 mRNA in the generation of
genetically-modified rats and mice as well as probably some other mammals.
PMID- 26442879
TI - Enzymatic pretreatment of low-grade oils for biodiesel production.
AB - The alkaline process for making biodiesel (fatty acid methyl esters, or FAME) is
highly efficient at the transesterification of glycerides. However, its
performance is poor when it comes to using oil that contain significant amounts
of free fatty acids (FFA). The traditional approach to such feedstocks is to
employ acid catalysis, which is slow and requires a large excess of methanol, or
to evaporate FFA and convert that in a separate process. An attractive option
would be to convert the FFA in oil feedstocks to FAME, before introducing it into
the alkaline process. The high selectivity of enzyme catalysis makes it a
suitable basis for such a pretreatment process. In this work, we present a
characterization of the pretreatment of high-FFA rapeseed oil using immobilized
Candida antarctica lipase B (Novozym 435), focused on the impact of initial FFA
and methanol concentration. Based on experimental results, we have identified
limitations for the process in terms of FFA concentration in the feedstock and
make suggestions for process operation. It was found that, using 5% catalyst and
4% methanol at 35 degrees C, the FFA concentration could be reduced to 0.5%
within an hour for feedstock containing up to 15% FFA. Further, the reaction was
observed to be under kinetic control, in that the biocatalyst converts FFA (and
FAME) at a much higher rate than glyceride substrates. There is thus, both a
minimum and a maximum reaction time for the process to achieve the desired
concentration of FFA. Finally, an assessment of process stability in a continuous
packed bed system indicates that as much as 15 m(3) oil could potentially be
pretreated by 1 kg of biocatalyst at the given process conditions.
PMID- 26442880
TI - Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the
AMPK-mTOR pathway.
AB - Autophagy plays an important role in liver triglyceride (TG) metabolism.
Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen
sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed
H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver
disease (NAFLD), while the mechanism remains to be explored. Here, we tested the
hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating
liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in
patients with HTG was lower than that of control subjects. Sodium hydrosulfide
(NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a
high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ),
an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased
the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH
increased the phosphorylation of AMPK and thus reduced the phosphorylation of
mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced
the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed
by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked
the autophagic enhancing effects of NaSH. The same qualitative effect was
observed in AMPKalpha2(-/-) mice. These results for the first time demonstrated
that H2S could reduce serum TG level and ameliorate NAFLD by activating liver
autophagy via the AMPK-mTOR pathway.
PMID- 26442882
TI - A Palladium- and Copper-Catalyzed Synthesis of Dihydro[1,2-b]indenoindole-9-ol
and Benzofuro[3,2-b]indolines: Metal-Controlled Intramolecular C-C and C-O Bond
Forming Reactions.
AB - A palladium- and copper-catalyzed synthesis of dihydro[1,2-b]indenoindole-9-ol
and benzofuro[3,2-b]indolines has been developed, whereby the same starting
material is employed for the synthesis of both heterocyclic scaffolds and the
selectivity of the product is controlled by switching the choice of metal.
Salient features of these cascade reactions include wide-ranging functional group
tolerance, simple reaction conditions, and moderate to high yields.
PMID- 26442881
TI - Acute ingestion of citrulline stimulates nitric oxide synthesis but does not
increase blood flow in healthy young and older adults with heart failure.
AB - To determine if age-associated vascular dysfunction in older adults with heart
failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed
two separate studies: 1) a kinetic study with a stable isotope tracer method to
determine in vivo kinetics of NO metabolism, and 2) a vascular function study
using a plethysmography method to determine reactive hyperemic forearm blood flow
(RH-FBF) in older and young adults in the fasted state and in response to
citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ~
50% lower in older vs. young adults and was related to a decreased rate of
appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de
novo arginine synthesis in both older [6.88 +/- 0.83 to 35.40 +/- 4.90 MUmol . kg
body wt(-1) . h(-1)] and to a greater extent in young adults (12.02 +/- 1.01 to
66.26 +/- 4.79 MUmol . kg body wt(-1) . h(-1)). NO synthesis rate increased
correspondingly in older (0.17 +/- 0.01 to 2.12 +/- 0.36 MUmol . kg body wt(-1) .
h(-1)) and to a greater extent in young adults (0.36 +/- 0.04 to 3.57 +/- 0.47
MUmol . kg body wt(-1) . h(-1)). Consistent with the kinetic data, RH-FBF in the
fasted state was ~ 40% reduced in older vs. young adults. However, citrulline
ingestion (10 g) failed to increase RH-FBF in either older or young adults. In
conclusion, citrulline ingestion improved impaired NO synthesis in older HF
adults but not RH-FBF, suggesting that factors other than NO synthesis play a
role in the impaired RH-FBF in older HF adults, and/or it may require a longer
duration of supplementation to be effective in improving RH-FBF.
PMID- 26442883
TI - A new agenda for mental health in the Eastern Mediterranean Region.
PMID- 26442884
TI - Comprehensive mental health action plan 2013-2020.
PMID- 26442885
TI - From plan to framework: the process for developing the regional framework to
scale up action on mental health in the Eastern Mediterranean Region.
PMID- 26442886
TI - Situational analysis: preliminary regional review of the Mental Health Atlas
2014.
AB - The WHO comprehensive Mental Health Action Plan 2013-2020 established goals and
objectives that Member States have agreed to meet by 2020. To update the Atlas of
Mental Health 2011, specific indicators from the Mental Health Action Plan and
additional indicators on service coverage were incorporated into the
questionnaire for the Atlas 2014. The data will help facilitate improvement in
information gathering and focus efforts towards implementation of the Mental
Health Action Plan. The questionnaire was completed by the national mental health
focal point of each country. This preliminary review seeks to consolidate data
from the initial response to the Atlas 2014 questionnaire by Member States in the
Eastern Mediterranean Region. Data for this review were analysed for the whole
Region, by health systems groupings and by individual countries. Where possible,
data are compared with the Mental Health Atlas 2011 to give a longitudinal
perspective.
PMID- 26442887
TI - Reorganization of mental health services: from institutional to community-based
models of care.
AB - Mental health services in the Eastern Mediterranean Region are predominantly
centralized and institutionalized, relying on scarce specialist manpower. This
creates a major treatment gap for patients with common and disabling mental
disorders and places an unnecessary burden on the individual, their family and
society. Six steps for reorganization of mental health services in the Region can
be outlined: (1) integrate delivery of interventions for priority mental
disorders into primary health care and existing priority programmes; (2)
systematically strengthen the capacity of non-specialized health personnel for
providing mental health care; (3) scale up community-based services (community
outreach teams for defined catchment, supported residential facilities, supported
employment and family support); (4) establish mental health services in general
hospitals for outpatient and acute inpatient care; (5) progressively reduce the
number of long-stay beds in mental hospitals through restricting new admissions;
and (6) provide transitional/bridge funding over a period of time to scale up
community-based services and downsize mental institutions in parallel.
PMID- 26442888
TI - Informing mental health policies and services in the EMR: cost-effective
deployment of human resources to deliver integrated community-based care.
AB - For EMR countries to deliver the expectations of the Global Mental Health Action
Plan 2013-2020 & the ongoing move towards universal health coverage, all health &
social care providers need to innovate and transform their services to provide
evidence-based health care that is accessible, cost-effective & with the best
patient outcomes. For the primary and community workforce, this includes general
medical practitioners, practice & community nurses, community social workers,
housing officers, lay health workers, nongovernmental organizations & civil
society, including community spiritual leaders/healers. This paper brings
together the current best evidence to support transformation & discusses key
approaches to achieve this, including skill mix and/or task shifting and
integrated care. The important factors that need to be in place to support skill
mix/task shifting and good integrated care are outlined with reference to EMR
countries.
PMID- 26442889
TI - Integration of mental health into priority health service delivery platforms:
maternal and child health services.
AB - Maternal and child health (MCH) programmes are the most logical and appropriate
platforms for integration of mental health care in an equitable, accessible and
holistic manner. Such integration has the potential to improve both mental and
physical health synergistically. Key steps to successful integration include a)
recognition, at the highest international and national policy forums, that mental
health and well-being is a generic component of MCH that does not compete with
MCH programmes but instead complements them; b) tailoring the training and
supervision of MCH and primary care personnel so they can recognize and assist in
the management of common maternal and child mental health problems, recognizing
that this, in turn, will enable them to be more effective health-care workers; c)
adapting effective interventions to local contexts; and d) investing in
implementation research so that these approaches are refined and scaled-up,
leading to improved outcomes for all MCH programmes.
PMID- 26442890
TI - Mental health and psychosocial support in humanitarian emergencies.
AB - Armed conflicts and natural disasters impact negatively on the mental health and
well-being of affected populations in the short- and long-term and affect the
care of people with pre-existing mental health conditions. This paper outlines
specific actions for mental health and psychosocial support by the health sector
in the preparedness, response and recovery phases of emergencies. Broad
recommendations for ministries of health are to: (1) embed mental health and
psychosocial support in national health and emergency preparedness plans; (2) put
in place national guidelines, standards and supporting tools for the provision of
mental health and psychosocial support during emergencies; (3) strengthen the
capacity of health professionals to identify and manage priority mental disorders
during emergencies; and (4) utilize opportunities generated by the emergency
response to contribute to development of sustainable mental health-care services.
PMID- 26442891
TI - Promotion of mental health and prevention of mental disorders: priorities for
implementation.
AB - There is compelling evidence from high-quality studies that mental health
promotion and primary prevention interventions can reduce the risk of mental
disorders, enhance protective factors for good mental and physical health, and
lead to lasting positive effects on a range of social and economic outcomes. This
paper reviews the available evidence in order to guide the implementation of
mental health promotion and prevention interventions in the Eastern Mediterranean
Region. The paper identifies a number of priority areas that can generate clear
health and social gains in the population and be implemented and sustained at a
reasonable cost. The interventions cover population groups across the lifespan
from infancy to adulthood and include actions delivered across different settings
and delivery platforms. "Best practices" were identified as interventions for
which there is evidence not only of their effectiveness but also of their
feasibility within resource constraints. The implications of the findings for
capacity development are considered.
PMID- 26442892
TI - Mental health surveillance and information systems.
AB - Routine information systems for mental health in many Eastern Mediterranean
Region countries are rudimentary or absent, making it difficult to understand the
needs of local populations and to plan accordingly. Key components for mental
health surveillance and information systems are: national commitment and
leadership to ensure that relevant high quality information is collected and
reported; a minimum data set of key mental health indicators; intersectoral
collaboration with appropriate data sharing; routine data collection supplemented
with periodic surveys; quality control and confidentiality; and technology and
skills to support data collection, sharing and dissemination. Priority strategic
interventions include: (1) periodically assessing and reporting the mental health
resources and capacities available using standardized methodologies; (2) routine
collection of information and reporting on service availability, coverage and
continuity, for priority mental disorders disaggregated by age, sex and
diagnosis; and (3) mandatory recording and reporting of suicides at the national
level (using relevant ICD codes).
PMID- 26442893
TI - Mental health research: developing priorities and promoting its utilization to
inform policies and services.
AB - Investment in research on the prevention and treatment of mental health disorders
is disproportionately low in the WHO Eastern Mediterranean Region (EMR) relative
to the disease burden. Scaling-up mental health research in the EMR could
generate enormous returns in terms of reducing disability, improving outcomes and
preventing premature death, through early diagnosis, better management and
community-based rehabilitation. EMR countries must therefore work to identify
research priorities, mobilize resources, develop human and infrastructure
capacities and institutionalize use of research findings to guide development of
policies and service delivery models. Several key strategic interventions for EMR
Member States are recommended: adopt a prioritized national mental health
research agenda; systematically map national and international research funding
to identify and secure resources to support the implementation of the agenda;
strengthen national capacity to undertake prioritized research; periodically map
research output in mental health; and foster dialogue between researchers and
policy-makers/programme managers.
PMID- 26442894
TI - Mental health policy and strategic plan.
PMID- 26442895
TI - Mental health legislation.
PMID- 26442896
TI - Investing in mental health.
PMID- 26442898
TI - WHO events addressing public health priorities.
PMID- 26442897
TI - Scaling up action for mental health in the Eastern Mediterranean Region: an
overview.
PMID- 26442899
TI - Comparison of parasitological, immunological and molecular methods for evaluation
of fecal samples of immunosuppressed rats experimentally infected with
Strongyloides venezuelensis.
AB - Definitive diagnosis of strongyloidiasis in humans is typically achieved by
detection of larvae in fecal samples. However, limitations on sensitivity of
parasitological methods emphasize the need for more robust diagnostic methods.
The aim of this study was to compare the diagnostic value of three methods: eggs
per gram of feces (EPG), coproantigen detection by enzyme linked immunosorbent
assay (ELISA), and DNA detection by conventional polymerase chain reaction (PCR).
The assays were performed at 0 and 5, 8, 13, 21 and 39 days post-infection (dpi)
using fecal samples from experimentally infected immunocompetent and
immunosuppressed rats. In immunocompetent rats, eggs were detected in feces on
days 5, 8 and 13 dpi; coproantigen detection and PCR amplification were
successful at all post-infection time points (5, 8, 13, 21 and 39 dpi). In
immunosuppressed rats, eggs were detected at 5, 8, 13 and 21; coproantigen
detection and PCR amplification were successful at all post-infection time
points. In conclusion, these results suggest that coproantigen detection and PCR
may be more sensitive alternatives to traditional methods such as EPG for
diagnosis of Strongyloides venezuelensis infection.
PMID- 26442900
TI - Exercise at Different Ages and Appendicular Lean Mass and Strength in Later Life:
Results From the Berlin Aging Study II.
AB - BACKGROUND: Excessive loss of muscle mass in advanced age is a major risk factor
for decreased physical ability and falls. Physical activity and exercise training
are typically recommended to maintain muscle mass and prevent weakness. How
exercise in different stages of life relates to muscle mass, grip strength, and
risk for weakness in later life is not well understood. METHODS: Baseline data on
891 participants at least 60 years old from the Berlin Aging Study II (BASE-II)
were analyzed. Linear and logistic regressions of self-reported exercise in early
adulthood, old age, or both on appendicular lean mass (ALM), grip strength, and a
risk indicator for weakness (ALM/ body mass index cutoff) were calculated. In
addition, treatment bounds are analyzed to address potential confounding using a
method proposed by Oster. RESULTS: Analyses indicate that for men only,
continuous exercise is significantly associated with higher muscle mass (SD =
0.24, p < .001), grip strength (SD = 0.18, p < .05), and lower risk for
clinically relevant low muscle mass (odds ratio = 0.36, p < .01). Exercise in
early adulthood alone is not significantly associated with muscle mass or
strength. No significant associations were observed for women. CONCLUSIONS: The
results of the current study underscore the importance of health programs to
promote physical activity with a focus on young adults, a group known to be
affected from environmentally associated decline of physical activity, and to
promote the continuation of physical exercise from early adulthood into later
life in general.
PMID- 26442901
TI - Rapamycin Increases Mortality in db/db Mice, a Mouse Model of Type 2 Diabetes.
AB - We examined the effect of rapamycin on the life span of a mouse model of type 2
diabetes, db/db mice. At 4 months of age, male and female C57BLKSJ-lepr (db/db)
mice (db/db) were placed on either a control diet, lacking rapamycin or a diet
containing rapamycin and maintained on these diets over their life span.
Rapamycin was found to reduce the life span of the db/db mice. The median
survival of male db/db mice fed the control and rapamycin diets was 349 and 302
days, respectively, and the median survival of female db/db mice fed the control
and rapamycin diets was 487 and 411 days, respectively. Adjusting for gender
differences, rapamycin increased the mortality risk 1.7-fold in both male and
female db/db mice. End-of-life pathological data showed that suppurative
inflammation was the main cause of death in the db/db mice, which is enhanced
slightly by rapamycin treatment.
PMID- 26442902
TI - Effects of citrate dialysate in chronic dialysis: a multicentre randomized
crossover study.
AB - BACKGROUND: Although citrate dialysate (CiDi) is regarded to be safe, dialysis
modalities using higher dialysate volumes, like haemodiafiltration (HDF), may
expose patients to higher citrate load and thus increase the risk of
complications. We investigated the residual risk of CiDi compared with standard
dialysate (StDi) in patients on different dialysis modalities and its effect on
dialysis dose. METHODS: In a multicentre randomized crossover study, 92 dialysis
patients (HDF post-dilution: n = 44, HDF pre-dilution: n = 26, haemodialysis: n =
25) were treated for 4 weeks with each dialysate (StDi and CiDi). Hypocalcaemia
(ionized calcium <=0.9 mmol/L), alkalosis (pH >=7.55), post-treatment bicarbonate
>=32 mmol/L, pre-treatment bicarbonate >=27 mmol/L, intra-dialytic events (IEs)
and adverse events (AEs) between dialysis sessions were investigated as primary
end points. The secondary objective was dialysis efficacy, i.e. dose and removal
ratios of urea, creatinine, phosphate and beta-2-microglobulin. RESULTS: Post
dialysis overcorrection of bicarbonate (>32 mmol/L) was less frequent with CiDi
(P = 0.008). Other predefined calcium and acid-base disturbances did not vary.
There was no significant difference in IE. However, more patients developed AEs
such as fatigue, muscle spasms or pain using CiDi (StDi: 41 versus CiDi: 55
patients, P = 0.02), particularly in the first 2 weeks of exposure. Dialysis
efficacy was comparable with both dialysates. CONCLUSIONS: It can be confirmed
that CiDi is not associated with the development of severe calcium and acid-base
disorders, even when dialysis modalities with higher citrate loads are used.
However, a refinement of the CiDi composition to minimize AEs is necessary.
PMID- 26442904
TI - Should women abstain from alcohol throughout pregnancy?
PMID- 26442903
TI - Reduced skeletal muscle function is associated with decreased fiber cross
sectional area in the Cy/+ rat model of progressive kidney disease.
AB - BACKGROUND: The combination of skeletal muscle wasting and compromised function
plays a role in the health decline commonly observed in chronic kidney disease
(CKD) patients, but the pathophysiology of muscle mass/strength changes remains
unclear. The purpose of this study was to characterize muscle properties in the
Cy/+ rat model of spontaneously progressive CKD. METHODS: Leg muscle function and
serum biochemistry of male Cy/+ (CKD) rats and their nonaffected littermates
(NLs) were assessed in vivo at 25, 30 and 35 weeks of age. Architecture and
histology of extensor digitorum longus (EDL) and soleus (SOL) muscles were
assessed ex vivo at the conclusion of the experiment. We tested the hypothesis
that animals with CKD have progressive loss of muscle function, and that this
functional deficit is associated with loss of muscle mass and quality. RESULTS:
Thirty-five-week-old CKD rats produced significantly lower maximum torque in
ankle dorsiflexion and shorter time to maximum torque, and longer half relaxation
time in dorsiflexion and plantarflexion compared with NL rats. Peak dorsiflexion
torque (but not plantarflexion torque) in CKD remained steady from 25 to 35
weeks, while in NL rats, peak torque increased. Mass, physiologic cross-sectional
area (CSA) and fiber-type (myosin heavy chain isoform) proportions of EDL and SOL
were not different between CKD and NL. However, the EDL of CKD rats showed
reduced CSAs in all fiber types, while only MyHC-1 fibers were decreased in area
in the SOL. CONCLUSIONS: The results of this study demonstrate that muscle
function progressively declines in the Cy/+ rat model of CKD. Because whole
muscle mass and architecture do not vary between CKD and NL, but CKD muscles show
reduction in individual fiber CSA, our data suggest that the functional decline
is related to increased muscle fiber atrophy.
PMID- 26442905
TI - The experimental teaching reform in biochemistry and molecular biology for
undergraduate students in Peking University Health Science Center.
AB - Since 2010, second-year undergraduate students of an eight-year training program
leading to a Doctor of Medicine degree or Doctor of Philosophy degree in Peking
University Health Science Center (PKUHSC) have been required to enter the
"Innovative talent training project." During that time, the students joined a
research lab and participated in some original research work. There is a critical
educational need to prepare these students for the increasing accessibility of
research experience. The redesigned experimental curriculum of biochemistry and
molecular biology was developed to fulfill such a requirement, which keeps two
original biochemistry experiments (Gel filtration and Enzyme kinetics) and adds a
new two-experiment component called "Analysis of anti-tumor drug induced
apoptosis." The additional component, also known as the "project-oriented
experiment" or the "comprehensive experiment," consists of Western blotting and a
DNA laddering assay to assess the effects of etoposide (VP16) on the apoptosis
signaling pathways. This reformed laboratory teaching system aims to enhance the
participating students overall understanding of important biological research
techniques and the instrumentation involved, and to foster a better understanding
of the research process all within a classroom setting. Student feedback
indicated that the updated curriculum helped them improve their operational and
self-learning capability, and helped to increase their understanding of
theoretical knowledge and actual research processes, which laid the groundwork
for their future research work.
PMID- 26442907
TI - Ceftriaxone reverses ketamine-induced lasting EEG and astrocyte alterations in
juvenile mice.
AB - BACKGROUND: Ketamine, an N-methyl-d-aspartate receptor antagonist, is used as a
pediatric anesthetic because of its favorable safety profile. It is also being
investigated as an antidepressant. Unfortunately, ketamine causes adverse
reactions including hallucinations and is associated with a high prevalence of
abuse among adolescents. Although chronic ketamine use has been shown to produce
cognitive impairments even years following cessation, little is known about its
long-term consequences on adolescents. The beta-lactam ceftriaxone has been shown
to attenuate alcohol withdrawal, and alleviate early brain injury and memory
impairments following subarachnoid hemorrhage. However, its ability to reverse
the effects of adolescent ketamine exposure is not known. Previous data indicate
that ketamine causes a reduction in the number of Excitatory Amino Acid
Transporter Type 2 (EAAT2)-containing astrocytes. Additionally, the beta lactam
antibiotic ceftriaxone increased expression of EAAT2. As EAAT2 is a principal
mechanism of glutamate clearance from the synapse, the current study tests the
hypothesis that ceftriaxone may reverse functional consequences of ketamine
exposure. METHODS: We examined the effects of chronic ketamine in juvenile mice
as well as reversal by ceftriaxone using electroencephalography (EEG).
Subsequently, we assessed the effects of these treatments on markers of astrocyte
proliferation, using Glial Fibrillary Acidic Protein (GFAP), and function, as
evidenced by EAAT2. RESULTS: Juvenile mice exposed to chronic ketamine showed
lasting alterations in EEG measurements as well as markers of astrocyte number
and function. These alterations were reversed by ceftriaxone. CONCLUSIONS: Data
suggest that ceftriaxone may be able to ameliorate ketamine-induced long-term
disturbances in adolescent brains.
PMID- 26442909
TI - Ultrasensitive nonlinear absorption response of large-size topological insulator
and application in low-threshold bulk pulsed lasers.
AB - Dirac-like topological insulators have attracted strong interest in
optoelectronic application because of their unusual and startling properties.
Here we report for the first time that the pure topological insulator Bi2Te3
exhibited a naturally ultrasensitive nonlinear absorption response to
photoexcitation. The Bi2Te3 sheets with lateral size up to a few micrometers
showed extremely low saturation absorption intensities of only 1.1 W/cm(2) at 1.0
and 1.3 MUm, respectively. Benefiting from this sensitive response, a Q-switching
pulsed laser was achieved in a 1.0 MUm Nd:YVO4 laser where the threshold absorbed
pump power was only 31 mW. This is the lowest threshold in Q-switched solid-state
bulk lasers to the best of our knowledge. A pulse duration of 97 ns was observed
with an average power of 26.1 mW. A Q-switched laser at 1.3 MUm was also realized
with a pulse duration as short as 93 ns. Moreover, the mode locking operation was
demonstrated. These results strongly exhibit that Bi2Te3 is a promising optical
device for constructing broadband, miniature and integrated high-energy pulsed
laser systems with low power consumption. Our work clearly points out a
significantly potential avenue for the development of two-dimensional-material
based broadband ultrasensitive photodetector and other optoelectronic devices.
PMID- 26442910
TI - Copper(II) tetrafluoroborate complexes with the N(3),N(4)-bridging coordination
of 1-(tert-butyl)-1H-tetrazole: synthesis, crystal structure and magnetic
properties.
AB - 1-(tert-Butyl)-1H-tetrazole (L) reacts with copper(ii) tetrafluoroborate
hexahydrate to give the complexes [Cu2L8(H2O)2](BF4)4 (1) or [Cu3L6(H2O)6](BF4)6
(2) depending on the reaction conditions. These complexes, as well as compound L,
were characterized using single crystal X-ray analysis. Complex 1 was found to
comprise a dinuclear complex cation [Cu2L8(H2O)2](4+) (the Ci symmetry point
group), with six tetrazole ligands L showing monodentate N(4)-coordination, and
two ligands L providing two tetrazole ring N(3),N(4) bridges between the
copper(ii) cations; water molecules complete the distorted octahedral
coordination of the metal ions. Complex 2 includes a linear trinuclear complex
cation [Cu3L6(H2O)6](6+) (the S6 symmetry point group), in which neighbouring
copper(ii) cations are linked by three ligands L via tetrazole ring N(3),N(4)
bridges; central and terminal metal ions show octahedral CuN6 and CuN3O3
coordination cores, respectively. The temperature-dependent magnetic
susceptibility measurements of complex 2 revealed that the copper(ii) ions were
weakly ferromagnetically coupled showing a coupling constant J of 2.2 cm(-1) {H =
-2J(S1S2 + S2S3)}. The quantum-chemical investigation of the electronic structure
and basicity of ligand L was carried out.
PMID- 26442908
TI - Group 1 mGlu-family proteins promote neuroadaptation to ethanol and withdrawal
associated hippocampal damage.
AB - BACKGROUND: Group 1 mGlu-family proteins (i.e., mGlu) consist of mGlu1 and mGlu5
and their activity may influence voluntary ethanol intake. The present studies
sought to examine the influence of these receptors on the development of ethanol
dependence using in vitro and in vivo models of chronic, intermittent ethanol
(CIE). METHODS: Rat hippocampal explants were exposed to CIE with or without the
addition of mGlu1 antagonist (7-hydroxyimino)cyclopropa[b]chromen-1a-carboxylate
ethyl ester (CPCCOEt; 0.5, 1, and 3MUM) or mGlu5 antagonist (E)-2-methyl-6-styryl
pyridine (SIB-1893; 20, 100, and 200MUM) to assess sparing of withdrawal-induced
cytotoxicity. In a separate study, adult male rats were administered CIE with or
without the addition of oral administration of group 1 mGlu antagonist 2-methyl-6
(phenylethynyl)-pyridine (MPEP; 3mg/kg). Blood ethanol levels (BELs) were
determined at 0930h on Day 2 of Weeks 1, 2, and 3. Withdrawal behavior was
monitored during Day 6 of the third consecutive withdrawal. RESULTS: CIE produced
significant hippocampal cytotoxicity. These effects were attenuated by co
exposure to CPCCOEt (3MUM) with ethanol in the CA3. By contrast, these effects
were blocked by SIB-1893 (20MUM) in each primary cell layer. Oral administration
of MPEP with ethanol significantly attenuated behavioral effects of subsequent
withdrawal and reduced BELs. CONCLUSIONS: These data demonstrate that ethanol
activates group 1 mGlu-family proteins to promote withdrawal-associated
cytotoxicity in vitro and physical dependence in vivo. These findings suggest
that group 1 mGlu-family proteins may be therapeutic targets for treatment of
alcohol use disorders.
PMID- 26442911
TI - Discovery of Small-Molecule Nonfluorescent Inhibitors of Fluorogen-Fluorogen
Activating Protein Binding Pair.
AB - A new class of biosensors, fluorogen activating proteins (FAPs), has been
successfully used to track receptor trafficking in live cells. Unlike the
traditional fluorescent proteins (FPs), FAPs do not fluoresce unless bound to
their specific small-molecule fluorogens, and thus FAP-based assays are highly
sensitive. Application of the FAP-based assay for protein trafficking in high
throughput flow cytometry resulted in the discovery of a new class of compounds
that interferes with the binding between fluorogens and FAP, thus blocking the
fluorescence signal. These compounds are high-affinity, nonfluorescent analogs of
fluorogens with little or no toxicity to the tested cells and no apparent
interference with the normal function of FAP-tagged receptors. The most potent
compound among these, N,4-dimethyl-N-(2-oxo-2-(4-(pyridin-2-yl)piperazin-1
yl)ethyl)benzenesulfonamide (ML342), has been investigated in detail. X-ray
crystallographic analysis revealed that ML342 competes with the fluorogen,
sulfonated thiazole orange coupled to diethylene glycol diamine (TO1-2p), for the
same binding site on a FAP, AM2.2. Kinetic analysis shows that the FAP-fluorogen
interaction is more complex than a homogeneous one-site binding process, with
multiple conformational states of the fluorogen and/or the FAP, and possible
dimerization of the FAP moiety involved in the process.
PMID- 26442912
TI - Understanding ForteBio's Sensors for High-Throughput Kinetic and Epitope
Screening for Purified Antibodies and Yeast Culture Supernatant.
AB - Real-time and label-free antibody screening systems are becoming more popular
because of the increasing output of purified antibodies and antibody supernatant
from many antibody discovery platforms. However, the properties of the biosensor
can greatly affect the kinetic and epitope binning results generated by these
label-free screening systems. ForteBio human-specific ProA, anti-human IgG
quantitation (AHQ), anti-human Fc capture (AHC) sensors, and custom biotinylated
anti-human Fc capture (b-AHFc) sensors were evaluated in terms of loading
ability, regeneration, kinetic characterization, and epitope binning with both
purified IgG and IgG supernatant. AHC sensors proved unreliable for kinetic or
binning assays at times, whereas AHQ sensors showed poor loading and regeneration
abilities. ProA sensors worked well with both purified IgG and IgG supernatant.
However, the interaction between ProA sensors and the Fab region of the IgG with
VH3 germline limited the application of ProA sensors, especially in the epitope
binning experiment. In an attempt to generate a biosensor type that would be
compatible with a variety of germlines and sample types, we found that the custom
b-AHFc sensors appeared to be robust working with both purified IgG and IgG
supernatant, with little evidence of sensor-related artifacts.
PMID- 26442913
TI - Polypharmacology of Small-Molecule Modulators of the 5-Lipoxygenase Activating
Protein (FLAP) Observed via a High-throughput Lipidomics Platform.
AB - Leukotrienes (LTs) and related species are proinflammatory lipid mediators
derived from arachidonic acid (AA) that have pathological roles in autoimmune and
inflammatory conditions, cardiovascular diseases, and cancer. 5-Lipoxygenase
activating protein (FLAP) plays a critical accessory role in the conversion of AA
to LTA4, and its subsequent conversion to LTC4 by LTC4 synthase. Pharmacological
inhibition of FLAP results in a loss of LT production by preventing the
biosynthesis of both LTB4 and LTC4, making it an attractive target for the
treatment of inflammatory diseases in which LTs likely play a role. Small
molecule (SM) drugs often exhibit polypharmacology through various pathways,
which may explain the differential therapeutic efficacies of compounds sharing
structural similarity. We have profiled a series of SM FLAP modulators for their
selectivity across enzymes of AA cascade in human whole blood (HWB), using a
recently developed LC/MS (liquid chromatography-mass spectrometry)-based high
throughput lipidomics platform that monitors 122 eicosanoids in multiplex. Highly
efficient data acquisition coupled with fast and accurate data analysis allowed
facile compound profiling from ex vivo study samples. This platform allowed us to
quantitatively map the effects of those SMs on the entire AA cascade,
demonstrating its potential to discriminate structurally related compounds.
PMID- 26442917
TI - Marital Quality Buffers the Association Between Socioeconomic Status and
Ambulatory Blood Pressure.
AB - BACKGROUND: Socioeconomic status is robustly associated with rates of death and
disease. Psychophysiological stress processes are thought to account for a
portion of this association. PURPOSE: Although positive and supportive
relationships can buffer psychophysiological stress responses, no studies have
examined whether the quality of a primary adult relationship-marriage-may buffer
the negative association between socioeconomic status and stress-related disease
processes. METHODS: The current study examines the interaction between income and
marital quality (supportive vs. ambivalent) on individuals' daily ambulatory
blood pressure, a valid and reliable indicator of cardiovascular risk. RESULTS:
Results revealed that supportive marital relationships buffered the otherwise
higher ambulatory diastolic blood pressure associated with low income.
CONCLUSIONS: Results are consistent with the buffering hypothesis of social
support and suggest that a supportive spouse may buffer stress-related autonomic
processes linking low socioeconomic status to risk for cardiovascular disease.
PMID- 26442916
TI - Prevalence of Dietary Supplement Use by Athletes: Systematic Review and Meta
Analysis.
AB - BACKGROUND: Dietary supplements (DSs) are commercially available products
consumed as an addition to the usual diet and are frequently ingested by
athletes. OBJECTIVE: Our objective was to examine the prevalence of DS use by
athletes. DATA SOURCES: PubMed, Ovid MEDLINE, OVID Healthstar, and Cumulative
Index to Nursing and Allied Health were searched for original research articles
published up to August 2014. Search terms included specific sports, specific DSs,
and other terms. STUDY SELECTION: Studies were selected if they were written in
English, involved athletes, and provided a quantitative assessment of the
proportion of athletes using specific DSs. Percent of athletes using specific
DSs. SYNTHESIS OF DATA: Methodological quality of studies was assessed by three
reviewers using an 8-point scale that included evaluations for sampling methods,
sampling frame, sample size, measurement tools, bias, response rate, statistical
presentation, and description of the participant sample. Where there were at
least two investigations, meta-analysis was performed to obtain summary (pooled)
prevalence estimates (SPEs) on (1) DS use prevalence by sport and sex, (2) DS use
prevalence by elite versus non-elite athletic status, and (3) specific DS
prevalence for all athletic groups combined. Meta-analyses included evaluations
of homogeneity and publication bias. RESULTS: A total of 159 unique studies met
the review criteria. Methodological quality was generally low with an average +/-
standard deviation of 43 +/- 16% of available rating points. There was low
homogeneity for SPEs when compiled by sport, athletic status, and/or specific
DSs. Contributing to the lack of homogeneity were differences in studies'
objectives and types of assessments used (e.g., dietary surveys, interviews,
questionnaires). Despite these limitations, the data generally indicated that
elite athletes used DSs much more than their non-elite counterparts. For most
DSs, use prevalence was similar for men and women except that a larger proportion
of women used iron while a larger proportion of men used vitamin E, protein, and
creatine. No consistent change in use over time was observed because even the
earliest investigations showed relatively high use prevalence. CONCLUSION: It was
difficult to generalize regarding DS use by athletes because of the lack of
homogeneity among studies. Nonetheless, the data suggested that elite athletes
used dietary supplements far more than their non-elite counterparts; use was
similar for men and women with a few exceptions; use appeared to change little
over time; and a larger proportion of athletes used DSs compared with the general
US population. Improvements in study methodology should be considered in future
studies especially (1) defining DSs for participants; (2) querying for very
specific DSs; (3) using a variety of reporting timeframes (e.g., daily, 2-6
times/week, 1 time/week and <1 time/week); (4) reporting the sampling frame,
number of individuals solicited, and number responding; (5) reporting
characteristics of volunteers (and non-volunteers, if available); and (6) using
similar methods on several occasions to examine possible temporal trends among
athletes.
PMID- 26442918
TI - Investigating sesquiterpene biosynthesis in Ginkgo biloba: molecular cloning and
functional characterization of (E,E)-farnesol and alpha-bisabolene synthases.
AB - Ginkgo biloba is one of the oldest living tree species and has been extensively
investigated as a source of bioactive natural compounds, including bioactive
flavonoids, diterpene lactones, terpenoids and polysaccharides which accumulate
in foliar tissues. Despite this chemical diversity, relatively few enzymes
associated with any biosynthetic pathway from ginkgo have been characterized to
date. In the present work, predicted transcripts potentially encoding enzymes
associated with the biosynthesis of diterpenoid and terpenoid compounds,
including putative terpene synthases, were first identified by mining publicly
available G. biloba RNA-seq data sets. Recombinant enzyme studies with two of the
TPS-like sequences led to the identification of GbTPS1 and GbTPS2, encoding
farnesol and bisabolene synthases, respectively. Additionally, the phylogenetic
analysis revealed the two terpene synthase genes as primitive genes that might
have evolved from an ancestral diterpene synthase.
PMID- 26442919
TI - New Pointers for Surgical Staging of Borderline Ovarian Tumors.
AB - BACKGROUND: Surgical management of borderline ovarian tumors (BOTs) is similar to
that of ovarian cancer apart from lymphadenectomy. However, the complete
procedure including peritoneal washing, infracolic omentectomy and random
peritoneal biopsies remains a subject of controversy especially in presumed early
stage BOTs. To evaluate the prognostic value of complete surgical staging on
recurrence rates, recurrence free (RFS) and overall survival (OS) in a
multicentre cohort of BOTs. METHODS: This retrospective multicentre study
included 428 patients with BOTs diagnosed from January 1980 to December 2008.
Survival estimates were based on Kaplan-Meier calculations and RFS defined as the
time from the date of surgery to the date of recurrence. RESULTS: The median time
of follow-up was 94.9 months (range: 60.00-207.3). The overall recurrence rate
was 23.8 %. There was no difference in 5-year RFS between patients with and
without complete surgical staging 78.1 % (95 % CI 68.9-88.6) and 70.9 % (95 % CI
64.6-77.8), (p = 0.0806). In the whole cohort, 5-year OS was higher for patients
with complete surgical staging 98.4 % (95 % CI 96.8-1.0) and 93.8 % (95 % CI 88.1
1), (p = 0.0182) but this difference was not significant for patients with FIGO
stage I 98.6 % (95 % CI 96.7-1) and 92.7 % (95 % CI 83.4-1.0), p = 0.1275,
respectively. CONCLUSIONS: Complete staging surgery should be considered as a
cornerstone treatment for patients with advanced stage BOT but not for those with
stage I disease.
PMID- 26442920
TI - Clinicopathological Features and Outcome of Lung Cancer Patients with
Hematological Malignancy.
AB - PURPOSE: The aim of this study was to report the incidence of lung cancer in
patients with hematological malignancy (HM), as well as patient characteristics
and outcome. METHODS: We investigated 1503 consecutive patients treated for HM
and 1208 patients who underwent surgical resection for lung cancer. RESULTS: Lung
cancer with HM was observed in 12 patients (0.8 % of HM cases and 1.0 % of lung
cancer cases), including eight men who were smokers and four women who had never
smoked. The average Brinkman index was 1010, which suggested heavy smokers. In
synchronous cases, all four patients preceded to HM treatment; however, three
patients died from HM. In metachronous cases, during a mean 52.7 months after
treatment of lung cancer, three patients had HM. At a mean 41.4 months after HM
treatment, five patients had lung cancer and underwent surgery without serious
postoperative events. CONCLUSIONS: A second cancer tended to be detected within 5
years after treatment of the first cancer. Men with a history of heavy smoking
might be at risk for combined lung cancer and HM. Careful follow-up is
recommended within 5 years after treatment of the first cancer. Most lung cancer
detected synchronously with HM had poor prognosis. In metachronous cases,
surgical resection of lung cancer after treatment of HM was feasible and safe.
PMID- 26442921
TI - Predictors of Severe Morbidity After Cytoreductive Surgery and Hyperthermic
Intraperitoneal Chemotherapy for Patients With Colorectal Peritoneal
Carcinomatosis.
AB - BACKGROUND: Severe morbidity after cytoreductive surgery (CRS) followed by
hyperthermic intraperitoneal chemotherapy (HIPEC) is, besides the obvious short
term consequences, associated with impaired long-term outcomes. The risk factors
for severe morbidity in patients with peritoneal carcinomatosis (PC) of
colorectal origin are poorly defined. This study aimed to identify risk factors
for severe morbidity after CRS + HIPEC in patients with colorectal PC. METHODS:
Patients with colorectal PC who underwent CRS + HIPEC between 2007 and 2015 were
categorized and compared between those with and those without severe morbidity.
Risk factors were identified using logistic regression analysis. Morbidity was
graded according to the Clavien-Dindo classification, with grade 3 or higher
indicating severe morbidity. RESULTS: This study included 211 patients, of whom
53 patients (25.1%) experienced morbidity of grade 3 or higher. The identified
risk factors for severe morbidity were extensive prior surgery [odds ratio (OR)
4.3], a positive recent smoking history (OR 4.0), a poor physical performance
status (OR 2.9), and extensive cytoreduction (OR 1.2 per additional resection).
Patients with a greater number of risk factors more often had severe morbidity
and higher reoperation, readmission, and mortality rates. Furthermore, an
internally validated preoperative prediction model for severe morbidity with an
area under the curve of 70% was constructed. CONCLUSION: The current study
identified risk factors for severe morbidity after CRS + HIPEC in patients with
colorectal PC. Patients with a combination of risk factors have a substantial
risk of severe morbidity and therefore should be carefully selected for CRS +
HIPEC. The preoperative decision model can be a valuable additional tool in this
process of patient selection.
PMID- 26442922
TI - Acute Kidney Injury After Radical Cystectomy for Bladder Cancer is Associated
with Chronic Kidney Disease and Mortality.
AB - PURPOSE: The aim of this study was to investigate the prevalence of acute kidney
injury (AKI) after radical cystectomy, and evaluate its impact on chronic kidney
disease (CKD) and mortality. METHODS: The medical records of 866 patients who
underwent radical cystectomy for bladder cancer were reviewed. AKI was assessed
within 7 days after surgery according to the Acute Kidney Injury Network
criteria. The prevalence of AKI after surgery was examined, and the significance
of AKI for CKD and mortality was analyzed. RESULTS: Of 866 patients, 269 (31.1 %)
developed AKI in the first week after surgery. Of these, 231 (85.9 %) were at
stage 1, 32 (11.9 %) at stage 2, and 6 (2.2 %) at stage 3. Of 722 patients with a
preoperative Modification of Diet in Renal Disease estimated glomerular
filtration rate (eGFR) of >60 ml/min/1.73 m(2), CKD developed in 23.0 % (118/513)
of patients in the non-AKI group and 32.5 % (68/209) of patients in the AKI
group. Independent factors predicting new-onset CKD were a preoperative eGFR (p <
0.001), age (p = 0.011), urinary tract complication (p < 0.001) and AKI (p =
0.015). In all, 297 patients died (191 in the non-AKI group and 106 in the AKI
group). AKI also correlated significantly with overall survival (p = 0.001).
CONCLUSIONS: AKI is not only commonly encountered after radical cystectomy but is
also associated with higher CKD rates and mortality. There is a critical need for
strategies to increase the identification of patients at risk of postoperative
AKI, and to improve the management of patients, with an aim toward preventing AKI
and improving the treatment of AKI once it occurs.
PMID- 26442923
TI - S-1 Adjuvant Chemotherapy Earlier After Surgery Clinically Correlates with
Prognostic Factors for Advanced Gastric Cancer.
AB - BACKGROUND: S-1 adjuvant chemotherapy is commonly administered postoperatively
for stage II and III advanced gastric cancer. METHODS: This study included 113
patients treated with S-1 adjuvant chemotherapy after surgery for stage II and
III advanced gastric cancer. These patients were divided into 4 groups: group A
(n = 63), who had a longer duration (>=6 months) and earlier S-1 administration
(<=6 weeks) after surgery; group B (n = 16), who had a longer and later S-1
administration (>6 weeks) after surgery; group C (n = 27), who had a shorter
duration (<6 months) and earlier S-1 administration after surgery; and group D (n
= 7), who had a shorter and later S-1 administration after surgery. RESULTS: The
recurrence rates in groups A, B, C, and D were 15.7, 43.8, 44.4, and 57.1 %,
respectively (A vs. B, p < 0.05, A vs. C and D, p < 0.01). The survival time of
group A was significantly longer than that of other groups (p < 0.005). In
addition, the survival time of patients with severe complications was
significantly shorter than that of patients with non-severe complications (p <
0.05). An earlier S-1 administration after surgery was the only independent
prognostic factor in the multivariate analysis. CONCLUSIONS: The prognosis of
advanced gastric cancer was significantly related to the start of S-1 adjuvant
treatment within 6 weeks after surgery.
PMID- 26442924
TI - Influence of tumour stage at breast cancer detection on survival in modern times:
population based study in 173,797 patients.
AB - OBJECTIVES: To assess the influence of stage at breast cancer diagnosis, tumour
biology, and treatment on survival in contemporary times of better (neo-)adjuvant
systemic therapy. DESIGN: Prospective nationwide population based study. SETTING:
Nationwide Netherlands Cancer Registry. PARTICIPANTS: Female patients with
primary breast cancer diagnosed between 1999 and 2012 (n=173,797), subdivided
into two time cohorts on the basis of breast cancer diagnosis: 1999-2005
(n=80,228) and 2006-12 (n=93,569). MAIN OUTCOME MEASURES: Relative survival was
compared between the two cohorts. Influence of traditional prognostic factors on
overall mortality was analysed with Cox regression for each cohort separately.
RESULTS: Compared with 1999-2005, patients from 2006-12 had smaller (<= T1 65%
(n=60,570) v 60% (n=48,031); P<0.001), more often lymph node negative (N0 68%
(n=63,544) v 65% (n=52,238); P<0.001) tumours, but they received more
chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant
systemic therapy 60% (n=56,402) v 53% (n=42,185); P<0.001). Median follow-up was
9.8 years for 1999-2005 and 3.9 years for 2006-12. The relative five year
survival rate in 2006-12 was 96%, improved in all tumour and nodal stages
compared with 1999-2005, and 100% in tumours <= 1 cm. In multivariable analyses
adjusted for age and tumour type, overall mortality was decreased by surgery
(especially breast conserving), radiotherapy, and systemic therapies. Mortality
increased with progressing tumour size in both cohorts (2006-12 T1c v T1a: hazard
ratio 1.54, 95% confidence interval 1.33 to 1.78), but without a significant
difference in invasive breast cancers until 1 cm (2006-12 T1b v T1a: hazard ratio
1.04, 0.88 to 1.22), and independently with progressing number of positive lymph
nodes (2006-12 N1 v N0: 1.25, 1.17 to 1.32). CONCLUSIONS: Tumour stage at
diagnosis of breast cancer still influences overall survival significantly in the
current era of effective systemic therapy. Diagnosis of breast cancer at an early
tumour stage remains vital.
PMID- 26442926
TI - Variations of body composition, physical activity and caloric intake in
schoolchildren during national holidays.
AB - Scientific literature has described that a significant body weight increase in
schoolchildren occurs during some holiday periods (summer, winter, and
thanksgiving holidays), harming their health. In this regard, it is thought that
this phenomenon is mainly due to changes in eating habits and the variation in
levels of physical activity; however, this approach has not yet been explored
during national holidays (NAH) in Chile. PURPOSE: To determine any changes in
body composition, physical activity and caloric intake during NAH. METHODS: A
total of 46 schoolchildren (24 boys, age 10.5 +/- 0.5; BMI 21.7 +/- 4.7)
participated. Measurements were performed 2 days before and after the NAH (9
days). Weight was measured and fat percentage was established using the Slaughter
formula. Levels of physical activity were measured with accelerometers,
validating 3 weekdays and 1 weekend; caloric intake was established through a 24
h recall. RESULTS: Weight, percentage of fat and caloric intake increased
significantly (250 g, 2.2 % and 733.3 kcal, respectively; p < 0.05); however,
none of the variables of physical activity showed significant changes.
CONCLUSION: The change in caloric intake seems to be the main cause of weight and
fat gain during the NAH.
PMID- 26442925
TI - CD1A-positive cells and HSP60 (HSPD1) levels in keratoacanthoma and squamous cell
carcinoma.
AB - CD1a is involved in presentation to the immune system of lipid antigen derived
from tumor cells with subsequent T cell activation. Hsp60 is a molecular
chaperone implicated in carcinogenesis by, for instance, modulating the immune
reaction against the tumor. We have previously postulated a synergism between
CD1a and Hsp60 as a key factor in the activation of an effective antitumor immune
response in squamous epithelia. Keratoacantomas (KAs) are benign tumors that
however can transform into squamous cell carcinomas (SCCs), but the reasons for
this malignization are unknown. In a previous study, we found that CD1a-positive
cells are significantly more numerous in KA than in SCC. In this study, we
analyzed a series of KAs and SCCs by immunohistochemistry for CD1a and Hsp60. Our
results show that the levels of both are significantly lower in KA than in SCC
and support the hypothesis that KA may evolve towards SCC if there is a failure
of the local modulation of the antitumor immune response. The data also show that
immunohistochemistry for CD1a and Hsp60 can be of help in differential diagnosis
between KAs and well-differentiated forms of SCC.
PMID- 26442927
TI - Individual and Joint Associations of Methylenetetrahydrofolate Reductase C677T
Genotype and Plasma Homocysteine With Dyslipidemia in a Chinese Population With
Hypertension.
AB - We aimed to examine the cross-sectional associations of plasma total homocysteine
(tHcy) concentrations and methylenetetrahydrofolate reductase ( MTHFR) C677T
genotype with dyslipidemia. A total of 231 patients with mild-to-moderate
essential hypertension were enrolled from the Huoqiu and Yuexi communities in
Anhui Province, China. Plasma tHcy levels were measured by high-performance
liquid chromatography. Genotyping was performed by TaqMan allelic discrimination
technique. Compared with MTHFR 677 CC + CT genotype carriers, TT genotype
carriers had higher odds of hypercholesterolemia (adjusted odds ratio [OR] [95%
confidence interval (CI)]: 2.7 [1.4-5.2]; P = .004) and higher odds of abnormal
low-density lipoprotein cholesterol (adjusted OR [95% CI]: 2.3 [1.1-4.8]; P =
.030). The individuals with the TT genotype had higher concentrations of
log(tHcy) than those with the 677 CC + CT genotype (adjusted beta [standard
error]: .2 [0.03]; P < .001). Patients with tHcy >= 10 MUmol/L had significantly
higher odds of hypercholesterolemia (adjusted OR [95% CI]: 2.4 [1.2-4.7]; P =
.010). Furthermore, patients with both the TT genotype and the tHcy >= 10 MUmol/L
had the highest odds of hypercholesterolemia (adjusted OR [95% CI]: 4.1 [1.8
9.4]; P = .001) and low-density lipoprotein cholesterol (adjusted OR [95% CI]:
2.4 [1.0-6.0]; P = .064). This study suggests that both tHcy and the MTHFR C677T
gene polymorphism may be important determinants of the incidence of dyslipidemia
in Chinese patients with essential hypertension. Further studies are needed to
confirm the role of tHcy and the MTHFR C677T mutation in the development of
dyslipidemia in a larger sample.
PMID- 26442929
TI - Prevalence of primary headache disorders diagnosed according to ICHD-3 beta in
three different social groups.
AB - BACKGROUND: The aim of our study was to estimate the one-year prevalence of
primary headache disorders in three different social groups using the third
edition beta of the International Classification of Headache Disorders (ICHD-3
beta). MATERIAL AND METHODS: The study population included a total of 3124
participants: 1042 students (719 females, 323 males, mean age 20.6, age range 17
40), 1075 workers (146 females, 929 males, mean age 40.4, age range 21-67) and
1007 blood donors (484 females, 523 males, mean age 34.1, age range 18-64). We
used a semi-structured, validated face-to-face interview. RESULTS: The age
adjusted one-year prevalence of migraine in females was significantly higher (p <
0.001) in students (41.9%) than in workers (19.2%) and blood donors (18.7%). Age
adjusted prevalence of migraine among males did not differ among the three
groups: 4.5% in students, 4.9% in workers and 4.5% in blood donors. Age-adjusted
prevalence of tension-type headache (TTH) among females was almost the same in
students and blood donors (68.8% and 66.7%) but female workers had a lower
prevalence of TTH (57%). Age-adjusted prevalence of TTH among males did not
differ significantly between students and blood donors (55.8% and 58.1%) but male
workers had a significantly lower (p < 0.001) prevalence of TTH (30.7%). The
prevalence of chronic headache in students (TTH and/or migraine) was 3% and of
probable medication-overuse headache 3%, significantly more than in workers and
blood donors. CONCLUSION: Headache prevalence was high and differed markedly
among the three social groups. It is important that headache epidemiology also
focus on socially defined groups in order to target future preventive efforts.
PMID- 26442928
TI - Trends in colorectal cancer mortality in Europe: retrospective analysis of the
WHO mortality database.
AB - OBJECTIVE: To examine changes in colorectal cancer mortality in 34 European
countries between 1970 and 2011. DESIGN: Retrospective trend analysis. DATA
SOURCE: World Health Organization mortality database. POPULATION: Deaths from
colorectal cancer between 1970 and 2011. Profound changes in screening and
treatment efficiency took place after 1988; therefore, particular attention was
paid to the evolution of colorectal cancer mortality in the subsequent period.
MAIN OUTCOMES MEASURES: Time trends in rates of colorectal cancer mortality,
using joinpoint regression analysis. Rates were age adjusted using the standard
European population. RESULTS: From 1989 to 2011, colorectal cancer mortality
increased by a median of 6.0% for men and decreased by a median of 14.7% for
women in the 34 European countries. Reductions in colorectal cancer mortality of
more than 25% in men and 30% in women occurred in Austria, Switzerland, Germany,
the United Kingdom, Belgium, the Czech Republic, Luxembourg, and Ireland. By
contrast, mortality rates fell by less than 17% in the Netherlands and Sweden for
both sexes. Over the same period, smaller or no declines occurred in most central
European countries. Substantial mortality increases occurred in Croatia, the
former Yugoslav republic of Macedonia, and Romania for both sexes and in most
eastern European countries for men. In countries with decreasing mortality,
reductions were more important for women of all ages and men younger than 65
years. In the 27 European Union member states, colorectal cancer mortality fell
by 13.0% in men and 27.0% in women, compared with corresponding reductions of
39.8% and 38.8% in the United States. CONCLUSION: Over the past 40 years, there
has been considerable disparity in the level of colorectal cancer mortality
between European countries, as well as between men and women and age categories.
Countries with the largest reductions in colorectal cancer mortality are
characterised by better accessibility to screening services, especially
endoscopic screening, and specialised care.
PMID- 26442930
TI - Lateral inhibition in the somatosensory cortex during and between migraine
without aura attacks: Correlations with thalamocortical activity and clinical
features.
AB - BACKGROUND: We studied lateral inhibition in the somatosensory cortex of
migraineurs during and between attacks, and searched for correlations with
thalamocortical activity and clinical features. PARTICIPANTS AND METHODS:
Somatosensory evoked potentials (SSEP) were obtained by electrical stimulation of
the right median (M) or ulnar (U) nerves at the wrist or by simultaneous
stimulation of both nerves (MU) in 41 migraine without aura patients, 24 between
(MO), 17 during attacks, and in 17 healthy volunteers (HVs). We determined the
percentage of lateral inhibition of the N20-P25 component by using the formula
[(100)-MU/(M + U)*100]. We also studied high-frequency oscillations (HFOs)
reflecting thalamocortical activation. RESULTS: In migraine, both lateral
inhibition (MO 27.9% vs HVs 40.2%; p = 0.009) and thalamocortical activity (MO
0.5 vs HVs 0.7; p = 0.02) were reduced between attacks, but not during. In MO
patients, the percentage of lateral inhibition negatively correlated with days
elapsed since the last migraine attack (r = -0.510, p = 0.01), monthly attack
duration (r = -0.469, p = 0.02) and severity (r = -0.443, p = 0.03), but
positively with thalamocortical activity (r = -0.463, p = 0.02). CONCLUSIONS: We
hypothesize that abnormal migraine cycle-dependent dynamics of connectivity
between subcortical and cortical excitation/inhibition networks may contribute to
clinical features of MO and recurrence of attacks.
PMID- 26442931
TI - Direct DNA Lesion Reversal and Excision Repair in Escherichia coli.
AB - Cellular DNA is constantly challenged by various endogenous and exogenous
genotoxic factors that inevitably lead to DNA damage: structural and chemical
modifications of primary DNA sequence. These DNA lesions are either cytotoxic,
because they block DNA replication and transcription, or mutagenic due to the
miscoding nature of the DNA modifications, or both, and are believed to
contribute to cell lethality and mutagenesis. Studies on DNA repair in
Escherichia coli spearheaded formulation of principal strategies to counteract
DNA damage and mutagenesis, such as: direct lesion reversal, DNA excision repair,
mismatch and recombinational repair and genotoxic stress signalling pathways.
These DNA repair pathways are universal among cellular organisms. Mechanistic
principles used for each repair strategies are fundamentally different. Direct
lesion reversal removes DNA damage without need for excision and de novo DNA
synthesis, whereas DNA excision repair that includes pathways such as base
excision, nucleotide excision, alternative excision and mismatch repair, proceeds
through phosphodiester bond breakage, de novo DNA synthesis and ligation. Cell
signalling systems, such as adaptive and oxidative stress responses, although not
DNA repair pathways per se, are nevertheless essential to counteract DNA damage
and mutagenesis. The present review focuses on the nature of DNA damage, direct
lesion reversal, DNA excision repair pathways and adaptive and oxidative stress
responses in E. coli.
PMID- 26442932
TI - An Introduction to the Structure and Function of the Ribosome.
AB - E. coli continues to serve as a key model for the structure and function of the
ribosome, structures of ribosome from other organisms and domains of life have
also greatly contributed to our knowledge of protein synthesis. Many structural
models of the ribosome in a number of steps of the protein synthesis cycle have
been solved by cryo-electron microscopy (cryo-EM) and x-ray crystallography. This
chapter introduces the structure and dynamics of the ribosome based on these
structures and ends with a brief discussion of the many questions that the
structures leave unanswered. Protein synthesis is a multistep process, and the
structural features of the ribosome along with the large number of cofactors
reflect the complexity of translation. Numerous protein factors in addition to
the ribosome contribute to translation in bacteria during the steps of
initiation, elongation, termination, and recycling. These protein factors make
intimate contacts to key regions of the ribosome, and this aspect is discussed in
the chapter in light of our present understanding of the structure and function
of the ribosome. The intact ribosome contains three binding sites for substrate
tRNAs that are termed as the aminoacyl-tRNA site (A site), peptidyl-tRNA site (P
site), and exit-tRNA site (E site). These three binding sites span the interface
between the 30S and 50S subunits. The central activity of the ribosome is
catalysis of peptide bond formation. The region of the ribosome responsible for
catalyzing the reaction is called the peptidyl transferase center (PTC).
PMID- 26442934
TI - Nus Factors of Escherichia coli.
AB - The highly conserved Nus factors of bacteria were discovered as essential host
proteins for the growth of temperate phage lambda in Escherichia coli. Later,
their essentiality and functions in transcription, translation, and, more
recently, in DNA repair have been elucidated. Close involvement of these factors
in various gene networks and circuits is also emerging from recent genomic
studies. We have described a detailed overview of their biochemistry, structures,
and various cellular functions, as well as their interactions with other
macromolecules. Towards the end, we have envisaged different uncharted areas of
studies with these factors, including their participation in pathogenicity.
PMID- 26442933
TI - The EcoCyc Database.
AB - EcoCyc is a bioinformatics database available at EcoCyc.org that describes the
genome and the biochemical machinery of Escherichia coli K-12 MG1655. The long
term goal of the project is to describe the complete molecular catalog of the E.
coli cell, as well as the functions of each of its molecular parts, to facilitate
a system-level understanding of E. coli. EcoCyc is an electronic reference source
for E. coli biologists and for biologists who work with related microorganisms.
The database includes information pages on each E. coli gene, metabolite,
reaction, operon, and metabolic pathway. The database also includes information
on E. coli gene essentiality and on nutrient conditions that do or do not support
the growth of E. coli. The website and downloadable software contain tools for
analysis of high-throughput data sets. In addition, a steady-state metabolic flux
model is generated from each new version of EcoCyc. The model can predict
metabolic flux rates, nutrient uptake rates, and growth rates for different gene
knockouts and nutrient conditions. This review provides a detailed description of
the data content of EcoCyc and of the procedures by which this content is
generated.
PMID- 26442935
TI - Glycogen: Biosynthesis and Regulation.
AB - Glycogen accumulation occurs in Escherichia coli and Salmonella enterica serovar
Typhimurium as well as in many other bacteria. Glycogen will be formed when there
is an excess of carbon under conditions in which growth is limited because of the
lack of a growth nutrient, e.g., a nitrogen source. This review describes the
enzymatic reactions involved in glycogen synthesis and the allosteric regulation
of the first enzyme, ADP-glucose pyrophosphorylase. The properties of the enzymes
involved in glycogen synthesis, ADP-glucose pyrophosphorylase, glycogen synthase,
and branching enzyme are also characterized. The data describing the genetic
regulation of the glycogen synthesis are also presented. An alternate pathway for
glycogen synthesis in mycobacteria is also described.
PMID- 26442936
TI - Cell-to-Cell Signaling in Escherichia coli and Salmonella.
AB - Bacteria must be able to respond rapidly to changes in the environment to
survive. One means of coordinating gene expression relies on tightly regulated
and complex signaling systems. One of the first signaling systems that was
described in detail is quorum sensing (QS). During QS, a bacterial cell produces
and secretes a signaling molecule called an autoinducer (AI). As the density of
the bacterial population increases, so does the concentration of secreted AI
molecules, thereby allowing a bacterial species to coordinate gene expression
based on population density. Subsequent studies have demonstrated that bacteria
are also able to detect signal molecules produced by other species of bacteria as
well as hormones produced by their mammalian hosts. This type of signaling
interaction has been termed cell-to-cell signaling because it does not rely on a
threshold concentration of bacterial cells. This review discusses the three main
types of cell-to-cell signaling mechanisms used by Escherichia coli and
Salmonella: the LuxR process, in which E. coli and Salmonella detect signals
produced by other species of bacteria; the LuxS/AI-2 system, in which E. coli and
Salmonella participate in intra- and interspecies signaling; and the AI
3/epinephrine/norepinephrine system, in which E. coli and Salmonella recognize
self-produced AI, signal produced by other microbes, and/or the human stress
hormones epinephrine and/or norepinephrine.
PMID- 26442937
TI - Transfer RNA Modification: Presence, Synthesis, and Function.
AB - Transfer RNA (tRNA) from all organisms on this planet contains modified
nucleosides, which are derivatives of the four major nucleosides. tRNA from
Escherichia coli/Salmonella enterica serovar Typhimurium contains 33 different
modified nucleosides, which are all, except one (Queuosine [Q]), synthesized on
an oligonucleotide precursor, which by specific enzymes later matures into tRNA.
The structural genes for these enzymes are found in mono- and polycistronic
operons, the latter of which have a complex transcription and translation
pattern. The synthesis of the tRNA-modifying enzymes is not regulated similarly,
and it is not coordinated to that of their substrate, the tRNA. The synthesis of
some of them (e.g., several methylated derivatives) is catalyzed by one enzyme,
which is position and base specific, whereas synthesis of some has a very complex
biosynthetic pathway involving several enzymes (e.g., 2-thiouridines, N 6
cyclicthreonyladenosine [ct6A], and Q). Several of the modified nucleosides are
essential for viability (e.g., lysidin, ct6A, 1-methylguanosine), whereas the
deficiency of others induces severe growth defects. However, some have no or only
a small effect on growth at laboratory conditions. Modified nucleosides that are
present in the anticodon loop or stem have a fundamental influence on the
efficiency of charging the tRNA, reading cognate codons, and preventing missense
and frameshift errors. Those that are present in the body of the tRNA primarily
have a stabilizing effect on the tRNA. Thus, the ubiquitous presence of these
modified nucleosides plays a pivotal role in the function of the tRNA by their
influence on the stability and activity of the tRNA.
PMID- 26442939
TI - Escherich and Escherichia.
AB - The purpose of this essay is threefold: to give an outline of the life and the
various achievements of Theodor Escherich, to provide a background to his
discovery of what he called Bacterium coli commune (now Escherichia coli), and to
indicate the enormous impact of studies with this organism, long before it became
the cornerstone of research in bacteriology and in molecular biology.
PMID- 26442941
TI - The Aerobic and Anaerobic Respiratory Chain of Escherichia coli and Salmonella
enterica: Enzymes and Energetics.
AB - Escherichia coli contains a versatile respiratory chain that oxidizes 10
different electron donor substrates and transfers the electrons to terminal
reductases or oxidases for the reduction of six different electron acceptors.
Salmonella is able to use two more electron acceptors. The variation is further
increased by the presence of isoenzymes for some substrates. A large number of
respiratory pathways can be established by combining different electron donors
and acceptors. The respiratory dehydrogenases use quinones as the electron
acceptors that are oxidized by the terminal reductase and oxidases. The enzymes
vary largely with respect to their composition, architecture, membrane topology,
and the mode of energy conservation. Most of the energy-conserving dehydrogenases
(FdnGHI, HyaABC, HybCOAB, and others) and the terminal reductases (CydAB, NarGHI,
and others) form a proton potential (Deltap) by a redox-loop mechanism. Two
enzymes (NuoA-N and CyoABCD) couple the redox energy to proton translocation by
proton pumping. A large number of dehydrogenases and terminal reductases do not
conserve the redox energy in a proton potential. For most of the respiratory
enzymes, the mechanism of proton potential generation is known or can be
predicted. The H+/2e- ratios for most respiratory chains are in the range from 2
to 6 H+/2e-. The energetics of the individual redox reactions and the respiratory
chains is described and related to the H+/2e- ratios.
PMID- 26442938
TI - DNA Methylation.
AB - The DNA of Escherichia coli contains 19,120 6-methyladenines and 12,045 5
methylcytosines in addition to the four regular bases, and these are formed by
the postreplicative action of three DNA methyltransferases. The majority of the
methylated bases are formed by the Dam and Dcm methyltransferases encoded by the
dam (DNA adenine methyltransferase) and dcm (DNA cytosine methyltransferase)
genes. Although not essential, Dam methylation is important for strand
discrimination during the repair of replication errors, controlling the frequency
of initiation of chromosome replication at oriC, and the regulation of
transcription initiation at promoters containing GATC sequences. In contrast,
there is no known function for Dcm methylation, although Dcm recognition sites
constitute sequence motifs for Very Short Patch repair of T/G base mismatches. In
certain bacteria (e.g., Vibrio cholerae, Caulobacter crescentus) adenine
methylation is essential, and, in C. crescentus, it is important for temporal
gene expression, which, in turn, is required for coordinating chromosome
initiation, replication, and division. In practical terms, Dam and Dcm
methylation can inhibit restriction enzyme cleavage, decrease transformation
frequency in certain bacteria, and decrease the stability of short direct repeats
and are necessary for site-directed mutagenesis and to probe eukaryotic structure
and function.
PMID- 26442942
TI - Analysis of Altered Micro RNA Expression Profiles in Focal Cortical Dysplasia
IIB.
AB - Focal cortical dysplasia type IIB is a commonly encountered subtype of
developmental malformation of the cerebral cortex and is often associated with
pharmacoresistant epilepsy. In this study, to investigate the molecular etiology
of focal cortical dysplasia type IIB, the authors performed micro ribonucleic
acid (RNA) microarray on surgical specimens from 5 children (2 female and 3 male,
mean age was 73.4 months, range 50-112 months) diagnosed of focal cortical
dysplasia type IIB and matched normal tissue adjacent to the lesion. In all, 24
micro RNAs were differentially expressed in focal cortical dysplasia type IIB,
and the microarray results were validated using quantitative real-time polymerase
chain reaction (PCR). Then the putative target genes of the differentially
expressed micro RNAs were identified by bioinformatics analysis. Moreover,
biological significance of the target genes was evaluated by investigating the
pathways in which the genes were enriched, and the Hippo signaling pathway was
proposed to be highly related with the pathogenesis of focal cortical dysplasia
type IIB.
PMID- 26442940
TI - Biotin and Lipoic Acid: Synthesis, Attachment, and Regulation.
AB - Two vitamins, biotin and lipoic acid, are essential in all three domains of life.
Both coenzymes function only when covalently attached to key metabolic enzymes.
There they act as "swinging arms" that shuttle intermediates between two active
sites (= covalent substrate channeling) of key metabolic enzymes. Although biotin
was discovered over 100 years ago and lipoic acid 60 years ago, it was not known
how either coenzyme is made until recently. In Escherichia coli the synthetic
pathways for both coenzymes have now been worked out for the first time. The late
steps of biotin synthesis, those involved in assembling the fused rings, were
well described biochemically years ago, although recent progress has been made on
the BioB reaction, the last step of the pathway in which the biotin sulfur moiety
is inserted. In contrast, the early steps of biotin synthesis, assembly of the
fatty acid-like "arm" of biotin were unknown. It has now been demonstrated that
the arm is made by using disguised substrates to gain entry into the fatty acid
synthesis pathway followed by removal of the disguise when the proper chain
length is attained. The BioC methyltransferase is responsible for introducing the
disguise, and the BioH esterase is responsible for its removal. In contrast to
biotin, which is attached to its cognate proteins as a finished molecule, lipoic
acid is assembled on its cognate proteins. An octanoyl moiety is transferred from
the octanoyl acyl carrier protein of fatty acid synthesis to a specific lysine
residue of a cognate protein by the LipB octanoyltransferase followed by sulfur
insertion at carbons C-6 and C-8 by the LipA lipoyl synthetase. Assembly on the
cognate proteins regulates the amount of lipoic acid synthesized, and, thus,
there is no transcriptional control of the synthetic genes. In contrast,
transcriptional control of the biotin synthetic genes is wielded by a remarkably
sophisticated, yet simple, system, exerted through BirA, a dual-function protein
that both represses biotin operon transcription and ligates biotin to its cognate
proteins.
PMID- 26442943
TI - A relationship between spinal new bone formation in ankylosing spondylitis and
the sonographically determined Achilles tendon enthesophytes.
AB - Spinal new bone formation is a major but incompletely understood manifestation of
ankylosing spondylitis (AS). We explored the relationship between spinal new bone
formation and ultrasound (US)-determined Achilles enthesophytes to test the
hypothesis that spinal new bone formation is part of a generalized enthesis bone
forming phenotype. A multicenter, case control study of 225 consecutive AS
patients and 95 age/body mass index (BMI) matched healthy controls (HC) was
performed. US scans of Achilles tendons and cervical and lumbar spine radiographs
were obtained. All images were centrally scored by one investigator for US and
one for radiographs, blinded to medical data. The relation between syndesmophytes
(by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and the number of
syndesmophytes) and enthesophytes (with a semi-quantitative scoring of the US
findings) was investigated. AS patients had significantly higher US enthesophyte
scores than HCs (2.1(1.6) vs. 1.6(1.6); p = 0.004). The difference was
significant in males (p = 0.001) but not in females (p = 0.5). The enthesophyte
scores significantly correlated with mSASSS scores (rho = 0.274, p < 0.0001) with
the association even stronger in males (enthesophyte scores vs. mSASSS rho =
0.337, p < 0.0001). In multiple regression analysis, age, BMI, enthesophyte
scores and disease duration were significantly associated with syndesmophytes in
males, and keeping all other variables constant, increasing US enthesophyte
scores increased the odds of having syndesmophytes by 67%. Male AS patients that
have more severe US-determined Achilles enthesophyte also associated spinal
syndesmophytes suggesting a bone-forming gender-specific phenotype that could be
a useful marker predicting of new bone formation.
PMID- 26442945
TI - Erotomania and Recommendations for Treatment.
AB - The aim of this paper is to help clinicians better understand how erotomania
originates in order to facilitate treatment and make it more effective. Data
sources are the narratives of six women who spoke in detail about the beginnings
of their delusional beliefs and about the nature of the evidence that convinced
them that their beliefs were well-founded. In every case, low self-esteem and
emotional arousal preceded the emergence of the delusion. Misperceptions and
misattributions appeared responsible for keeping the delusion alive. Despite
external disconfirmation, social isolation protected the delusional beliefs from
revision and extinction. The erotomanic delusion provided a sense of well-being
that probably contributed to its maintenance. As well, a delusion-induced boost
in well-being delayed help-seeking. Recommendations for treatment include staged
interventions, first establishing a therapeutic alliance with a focus on
understanding the psychological factors contributing to the origin and
maintenance of the delusion. The next stage is the provision of social support
and strategies directed at the restoration of self-esteem. The third stage is the
gradual introduction of techniques to correct cognitive biases. Medication and
risk management form an integral part of overall management. Objective evidence
for the effectiveness of this approach is, however, not yet available.
PMID- 26442944
TI - Comorbid Personality Disorders in Obsessive-Compulsive Disorder and Its Symptom
Dimensions.
AB - The current paper was aimed at: (1) investigating the comorbidity between
obsessive-compulsive disorder (OCD) and personality disorders (PDs) using an OCD
sample and clinician-administered structured interviews; (2) exploring the
associations of different cluster comorbid PDs with the specific symptom
dimensions of OCD; (3) analyzing the variables which could play a significant
role in the probability of having at least one comorbid PD, controlling for
confounding variables. The SCID-II and Y-BOCS, together with a series of self
report measures of OCD, depression and anxiety symptoms were administered to a
clinical sample of 159 patients with a primary diagnosis of OCD. 20.8 % of the
participants suffered from at least one comorbid PD; the most common was
obsessive-compulsive PD (9.4 %), followed by narcissistic PD (6.3 %). In OCD
patients with comorbid cluster C PDs, the percentage of responsibility for harm,
injury, or bad luck symptoms was significantly greater than other OCD symptom
dimensions (p < .005). Logistic regression found some evidence supporting the
association between severity of OCD symptoms and comorbid PDs. PDs are prevalent
among Italian people with OCD and should be routinely assessed, as comorbidity
may affect help-seeking behaviour and response to treatment.
PMID- 26442946
TI - Structural and Chemical Analysis of the Zirconia-Veneering Ceramic Interface.
AB - The interfacial interaction of veneering ceramic with zirconia is still not fully
understood. This study aimed to characterize morphologically and chemically the
zirconia-veneering ceramic interface. Three zirconia-veneering conditions were
investigated: 1) zirconia-veneering ceramic fired on sandblasted zirconia, 2)
zirconia-veneering ceramic on as-sintered zirconia, and 3) alumina-veneering
ceramic (lower coefficient of thermal expansion [CTE]) on as-sintered zirconia.
Polished cross-sectioned ceramic-veneered zirconia specimens were examined using
field emission gun scanning electron microscopy (Feg-SEM). In addition, argon-ion
thinned zirconia-veneering ceramic interface cross sections were examined using
scanning transmission electron microscopy (STEM)-energy dispersive X-ray
spectrometry (EDS) at high resolution. Finally, the zirconia-veneering ceramic
interface was quantitatively analyzed for tetragonal-to-monoclinic phase
transformation and residual stress using micro-Raman spectroscopy (uRaman). Feg
SEM revealed tight interfaces for all 3 veneering conditions. High-resolution
transmission electron microscopy (HRTEM) disclosed an approximately 1.0-um
transformed zone at sandblasted zirconia, in which distinct zirconia grains were
no longer observable. Straight grain boundaries and angular grain corners were
detected up to the interface of zirconia- and alumina-veneering ceramic with as
sintered zirconia. EDS mapping disclosed within the zirconia-veneering ceramic a
few nanometers thick calcium/aluminum-rich layer, touching the as-sintered
zirconia base, with an equally thick silicon-rich/aluminum-poor layer on top.
uRaman revealed t-ZrO2-to-m-ZrO2 phase transformation and residual compressive
stress at the sandblasted zirconia surface. The difference in CTE between
zirconia- and the alumina-veneering ceramic resulted in residual tensile stress
within the zirconia immediately adjacent to its interface with the veneering
ceramic. The rather minor chemical elemental shifts recorded in the veneering
ceramic did not suffice to draw definitive conclusions regarding potential
chemical interaction of the veneering ceramic with zirconia. Sandblasting damaged
the zirconia surface and induced phase transformation that also resulted in
residual compressive stress. Difference in CTE of zirconia versus that of the
veneering ceramic resulted in an unfavorable residual tensile stress at the
zirconia-veneering ceramic interface.
PMID- 26442947
TI - Effect of Industry Sponsorship on Dental Restorative Trials.
AB - Industry sponsorship was found to potentially introduce bias into clinical
trials. We assessed the effects of industry sponsorship on the design, comparator
choice, and findings of randomized controlled trials on dental restorative
materials. A systematic review was performed via MEDLINE, CENTRAL, and EMBASE.
Randomized trials on dental restorative and adhesive materials published 2005 to
2015 were included. The design of sponsored and nonsponsored trials was compared
statistically (risk of bias, treatment indication, setting, transferability,
sample size). Comparator choice and network geometry of sponsored and
nonsponsored trials were assessed via network analysis. Material performance
rankings in different trial types were estimated via Bayesian network meta
analysis. Overall, 114 studies were included (15,321 restorations in 5,232
patients). We found 21 and 41 (18% and 36%) trials being clearly or possibly
industry sponsored, respectively. Trial design of sponsored and nonsponsored
trials did not significantly differ for most assessed items. Sponsored trials
evaluated restorations of load-bearing cavities significantly more often than
nonsponsored trials, had longer follow-up periods, and showed significantly
increased risk of detection bias. Regardless of sponsorship status, comparisons
were mainly performed within material classes. The proportion of trials comparing
against gold standard restorative or adhesive materials did not differ between
trial types. If ranked for performance according to the need to re-treat (best:
least re-treatments), most material combinations were ranked similarly in
sponsored and nonsponsored trials. The effect of industry sponsorship on dental
restorative trials seems limited.
PMID- 26442948
TI - Neutrophil Extracellular Traps in Periodontitis: A Web of Intrigue.
AB - Neutrophil extracellular traps (NETs) represent a novel paradigm in neutrophil
mediated immunity. NETs are believed to constitute a highly conserved
antimicrobial strategy comprising decondensed nuclear DNA and associated histones
that are extruded into the extracellular space. Associated with the web-like
strands of DNA is an array of antimicrobial peptides (AMPs), which facilitate the
extracellular destruction of microorganisms that become entrapped within the
NETs. NETs can be released by cells that remain viable or following a unique form
of programmed cell death known as NETosis, which is dependent on the production
of reactive oxygen species (ROS) and the decondensing of the nuclear DNA
catalyzed by peptidyl arginine deiminase-4. NETs are produced in response to a
range of pathogens, including bacteria, viruses, fungi, and protozoa, as well as
host-derived mediators. NET release is, however, not without cost, as the
concomitant release of cytotoxic molecules can also cause host tissue damage.
This is evidenced by a number of immune-mediated diseases, in which excess or
dysfunctional NET production, bacterial NET evasion, and decreased NET removal
are associated with disease pathogenesis. Periodontitis is the most prevalent
infectious-inflammatory disease of humans, characterized by a dysregulated
neutrophilic response to specific bacterial species within the subgingival plaque
biofilm. Neutrophils are the predominant inflammatory cell involved in
periodontitis and have previously been found to exhibit hyperactivity and
hyperreactivity in terms of ROS production in chronic periodontitis patients.
However, the contribution of ROS-dependent NET formation to periodontal health or
disease remains unclear. In this focused review, we discuss the mechanisms,
stimuli, and requirements for NET production; the ability of NET-DNA and NET
associated AMPs to entrap and kill pathogens; and the potential immunogenicity of
NETs in disease. We also speculate on the potential role of NETs in the
pathogenesis of periodontitis.
PMID- 26442949
TI - Root and Eruption Defects in c-Fos Mice Are Driven by Loss of Osteoclasts.
AB - c-Fos homozygous mice lack osteoclasts with a failure of the teeth to erupt and
with an arrest of root development. Here, we characterize the defects associated
with the failure in root development and the loss of the tooth-bone interface,
and we investigate the underlying causes. We show that, while homozygous c-Fos
mice have no multinucleated osteoclasts, heterozygous mice have a reduction in
the number of osteoclasts with a reduction in the tooth-bone interface during
development and subtle skeletal defects postnatally. In the homozygous mutants
bone is found to penetrate the tooth, particularly at the apical end, physically
disrupting the root forming HERS (Hertwig's epithelial root sheath) cells. The
cells of the HERS continue to proliferate but cannot extend downward due to the
presence of bone, leading to a loss of root formation. Tooth germ culture showed
that the developing tooth invaded the static bone in mutant tissue, rather than
the bone encroaching on the tooth. Although c-Fos has been shown to be expressed
in developing teeth, the defect in maintenance of the tooth-bone interface
appears to be driven solely by the lack of osteoclasts, as this defect can be
rescued in the presence of donor osteoclasts. The rescue suggests that signals
from the tooth recruit osteoclasts to clear the bone from around the tooth,
allowing the tooth to grow, form roots, and later erupt.
PMID- 26442950
TI - The Microbiome in Populations with a Low and High Prevalence of Caries.
AB - The oral microbiota was compared between Romanian adolescents with a high
prevalence of caries and no dental care and Swedish caries-active and caries-free
adolescents in caries prevention programs and with a low prevalence of caries.
Biofilm samples were analyzed by FLX+ pyrosequencing of the V1 to V4
hypervariable regions of the 16S rRNA gene and polymerase chain reaction
(PCR)/quantitative PCR (qPCR) for Streptococcus mutans and Streptococcus
sobrinus. Sequences obtained blasted to 9 phyla, 66 genera, and 401 human oral
taxa (HOT) in the 16S rRNA Human Oral Microbiome Database, of which 295 were
represented by >=20 sequences. The Romanian adolescents had more sequences in
Firmicutes and fewer in Actinobacteria phyla and more sequences in the genera
Bacteroidetes [G-3], Porphyromonas, Abiotrophia, Filifactor,
Peptostreptococcaceae [11][G-4], Pseudoramibacter, Streptococcus, and Neisseria
and fewer in Actinomyces, Selenomonas, Veillonella, Campylobacter, and TM7 [G-1]
than the Swedish groups. Multivariate modeling employing HOT, S. sobrinus and S.
mutans (PCR/qPCR), and sugar snacks separated Romanian from Swedish adolescents.
The Romanian adolescents' microbiota was characterized by a panel of
streptococci, including S. mutans, S. sobrinus, and Streptococcus australis, and
Alloprevotella, Leptotrichia, Neisseria, Porphyromonas, and Prevotella. The
Swedish adolescents were characterized by sweet snacks, and those with caries
activity were also characterized by Prevotella, Actinomyces, and Capnocytophaga
species and those free of caries by Actinomyces, Prevotella, Selenomonas,
Streptococcus, and Mycoplasma. Eight species including Streptococcus mitis and
Streptococcus species HOT070 were prevalent in Romanian and Swedish caries-active
subjects but not caries-free subjects. In conclusion, S. mutans and S. sobrinus
correlated with Romanian adolescents with caries and with limited access to
dental care, whereas S. mutans and S. sobrinus were detected infrequently in
Swedish adolescents in dental care programs. Swedish caries-active adolescents
were typically colonized by Actinomyces, Selenomonas, Prevotella, and
Capnocytophaga. Hence, the role of mutans streptococci as a primary caries
pathogen appears less pronounced in populations with prevention programs compared
to populations lacking caries treatment and prevention strategies.
PMID- 26442952
TI - Predictors of Posttraumatic Stress Symptoms Among Adolescent and Young Adult
Survivors of Childhood Cancer: Importance of Monitoring Survivors' Experiences of
Family Functioning.
AB - The purpose of this study was to identify factors associated with posttraumatic
stress symptoms (PTSS) among Japanese long-term childhood cancer survivors
(CCSs). Subjects comprised 185 adolescent and young adult (AYA) CCSs who
completed anonymous self-report questionnaires. Attending physicians also
completed an anonymous disease/treatment data sheet. Mean age of survivors was
approximately 8 years at diagnosis and 23 years at participation. Multiple
regression analysis showed that family functioning, satisfaction with social
support, being female, and interactions between family functioning and gender and
age at the time of diagnosis were associated with PTSS among survivors. This
study revealed family functioning as the most predictive factor of PTSS among AYA
CCSs in Japan. Even when the survivor may have unchangeable risk factors, family
functioning can potentially moderate the effects on PTSS. Thus, it is crucial for
health professionals to carefully monitor and attend to survivors' experiences of
family functioning to mitigate PTSS.
PMID- 26442951
TI - Clinical Implications of Additional Pedal Artery Angioplasty in Critical Limb
Ischemia Patients With Infrapopliteal and Pedal Artery Disease.
AB - PURPOSE: To evaluate the clinical implications of additional pedal artery
angioplasty (PAA) for patients with critical limb ischemia (CLI). METHODS: Twenty
nine patients (mean age 77.8+/-8.6 years; 21 men) with CLI (32 limbs) presenting
with de novo infrapopliteal and pedal artery (Kawarada type 2/3) disease were
reviewed. The need for PAA was based on the existence of sufficient wound blush
(WB) around the target wounds after conventional above-the-ankle
revascularization. Fourteen patients with insufficient WB in 14 limbs received
additional PAA, while 15 patients with sufficient WB in 18 limbs did not. The
groups were compared for overall survival, limb salvage, and amputation-free
survival within 1 year after the procedure. The wound healing rate, time to wound
healing, and freedom from reintervention rate were also evaluated. RESULT: The
success rate of additional PAA was 93% (13/14). All limbs with successful PAA
achieved sufficient WB (13/13). Despite insufficient WB before the additional
PAA, overall survival (86% vs 73%, p=0.350), limb salvage (93% vs 83%, p=0.400),
amputation-free survival (79% vs 53%, p=0.102), and freedom from reintervention
(64% vs 73%, p=0.668) rates were similar in both groups. Furthermore, the wound
healing rate (93% vs 60%, p=0.05) was higher and time to wound healing (86.0+/
18.7 vs 152.0+/-60.2 days, p=0.05) was shorter in the patients who received PAA.
CONCLUSION: Additional PAA might improve the WB and clinical outcomes (especially
speed and extent of wound healing) in patients with CLI attributed to
infrapopliteal and pedal artery disease.
PMID- 26442954
TI - Beliefs of Palestinian Women From Israel About the Responsibility and Punishment
of Violent Husbands and About Helping Battered Women.
AB - This article presents a study that examined beliefs about violent husbands and
about helping battered women among Palestinian women living in Israel from the
perspective of patriarchal ideology. A convenience sample of 701 married women
was obtained, and a self-report questionnaire was administered. The findings
reveal that the majority of participants held violent husbands accountable for
their behavior; however, the majority of them did not support punishing violent
husbands through formal agencies (i.e., the police) or through informal social
institutions (i.e., the family). In addition, contrary to expectations, the
majority of women perceived wife beating as a social problem rather than as a
private one that should be dealt with within the family. Regression and multiple
regression analysis revealed that women's endorsement of patriarchal ideology was
found to influence all three above-mentioned beliefs about violent husbands and
battered women, over and above the amount of variance in each of these beliefs
that could be attributed to the women's sociodemographic characteristics. The
limitations of the study and its implications for future research are discussed.
PMID- 26442953
TI - SPINT2 Deregulation in Prostate Carcinoma.
AB - SPINT2 is a tumor suppressor gene that inhibits proteases implicated in cancer
progression, like HGFA, hepsin and matriptase. Loss of SPINT2 expression in
tumors has been associated with gene promoter hypermethylation; however, little
is known about the mechanisms of SPINT2 deregulation in prostate cancer (PCa). We
aimed to analyze SPINT2 expression levels and understand the possible regulation
by SPINT2 promoter hypermethylation in PCa. In a cohort of 57 cases including non
neoplastic and PCa tissues, SPINT2 expression and promoter methylation was
analyzed by immunohistochemistry and methylation-specific PCR, respectively.
Methylation status of the SPINT2 promoter was also evaluated by bisulfite
sequencing and 5-aza-2'-deoxycytidine treatment. Oncomine and TCGA databases were
used to perform in silico PCa analysis of SPINT2 mRNA and methylation levels. A
reduction in SPINT2 expression levels from non-neoplastic to PCa tissues was
observed; however, none of the cases exhibited SPINT2 promoter methylation. Both
bisulfite sequencing and 5-aza demonstrated that SPINT2 promoter is not
methylated in PCa cells. Bioinformatics approaches did not show downregulation of
SPINT2 at the mRNA level and, in corroboration with our results, SPINT2 promoter
region is reported to be unmethylated. Our study suggests an involvement of
SPINT2 in PCa tumorigenesis, probably in association with a post-translational
regulation of SPINT2.
PMID- 26442955
TI - Elder Abuse in a Developing Area in Bolivia.
AB - In many parts of the world, elder abuse happens almost unnoticed. Until recently,
this serious social problem was hidden from public view and was regarded as an
essentially private matter. However, there is growing evidence that elder abuse
is an important problem of public health and in the society. The objective of
this study is to determine the degree of abuse of elder and vulnerable people in
the families and communities of Eastern Bolivia. With this end in mind, we
conducted a cross-sectional descriptive study with a sample size of 210 60-year
old people coming from different health care areas. Elder Abuse Suspicion Index
(EASI) and Yaffe's Evaluation Form of Social Work were used. An abuse rate of 39%
of the older adults was identified. The most common type of abuse observed was
psychological abuse (32.4% of cases), followed by neglect (21.9%). Children were
identified as triggers of the abuse in 66.7% of cases of abuse. The prevalence of
elder abuse was similar to the prevalence of other types of abuse that exist in
Bolivia, such as the gender-based abuse. Also, this prevalence is comparable to
other developing countries and European countries. The profile of abused older
adult is as follows: woman, widow, 70 years old, incomplete primary education,
without an occupation, and an average of 4.59 children. The information obtained
shows that dysfunctional families have a higher percentage of elder abuse.
PMID- 26442956
TI - Lessons for Health From Insights into Environmental Crises.
AB - The health of whole populations within nations and globally and the implications
of climate change are two of the most important challenges facing humanity in the
21st century. Both are components of a complex global crisis that must be
acknowledged and addressed. Here we draw the attention of health professionals to
some emerging threats and insights from key works of environmentalists in the
hope that these may catalyze reflection on the broader challenges facing human
health at a time of deep planetary malaise.
PMID- 26442957
TI - Validation of the revised Mystical Experience Questionnaire in experimental
sessions with psilocybin.
AB - The 30-item revised Mystical Experience Questionnaire (MEQ30) was previously
developed within an online survey of mystical-type experiences occasioned by
psilocybin-containing mushrooms. The rated experiences occurred on average eight
years before completion of the questionnaire. The current paper validates the
MEQ30 using data from experimental studies with controlled doses of psilocybin.
Data were pooled and analyzed from five laboratory experiments in which
participants (n=184) received a moderate to high oral dose of psilocybin (at
least 20 mg/70 kg). Results of confirmatory factor analysis demonstrate the
reliability and internal validity of the MEQ30. Structural equation models
demonstrate the external and convergent validity of the MEQ30 by showing that
latent variable scores on the MEQ30 positively predict persisting change in
attitudes, behavior, and well-being attributed to experiences with psilocybin
while controlling for the contribution of the participant-rated intensity of drug
effects. These findings support the use of the MEQ30 as an efficient measure of
individual mystical experiences. A method to score a "complete mystical
experience" that was used in previous versions of the mystical experience
questionnaire is validated in the MEQ30, and a stand-alone version of the MEQ30
is provided for use in future research.
PMID- 26442958
TI - Cognitive Rest: An Integrated Literature Review.
AB - Cognitive rest has been suggested as a treatment for school athletes who have
sustained a concussion, but the concept has rarely been defined. The purpose of
this article is to provide a comprehensive definition of cognitive rest, based on
an integrative literature review. The method of synthesis was guided by Avant and
Walker's concept analysis format. The importance of rest is discussed as a
nursing intervention, and model cases are presented to clarify the concept. Three
defining attributes of cognitive rest are established: freedom from physical or
mental discomfort, abstinence from mental exertion, and mental and emotional
balance. Empirical referents are given as well as a suggested protocol to enable
school nurses to form cognitive rest and return-to-classroom protocols that can
be adapted to individual school settings.
PMID- 26442959
TI - Does nutritional counseling in telemedicine improve treatment outcomes for
diabetes? A systematic review and meta-analysis of results from 92 studies.
AB - BACKGROUND: A growing number of studies and reviews have documented the impact of
telemedicine on diabetes management. However, no meta-analysis has assessed
whether including nutritional counseling as part of a telemedicine program has a
significant impact on diabetes outcomes or what kind of nutritional counseling is
most effective. METHODS: Original research articles examining the effect of
telemedicine interventions on HbA1c levels in patients with Type 1 or Type 2
diabetes were included in this study. A literature search was performed and 92
studies were retained for analysis. We examined stratified results by
differentiating interventions using no nutritional counseling from those that
used nutritional counseling. We further compared between nutritional counseling
administered via short message systems (SMS) such as email and text messages, and
nutritional counseling administered via telephone or videoconference. RESULTS:
Telemedicine programs that include a nutritional component show similar effect in
diabetes management as those programs that do not. Furthermore, subgroup analysis
reveals that nutritional intervention via SMS such as email and text messages is
at least as equally effective in reducing HbA1c when compared to personal
nutritional counseling with a practitioner over videoconference or telephone.
CONCLUSION: The inclusion of nutritional counseling as part of a telemedicine
program does not make a significant difference to diabetes outcomes.
Incorporating nutritional counseling into telemedicine programs via SMS is at
least as effective as counseling via telephone or videoconference.
PMID- 26442960
TI - Understanding catalysis in a multiphasic two-dimensional transition metal
dichalcogenide.
AB - Establishing processing-structure-property relationships for monolayer materials
is crucial for a range of applications spanning optics, catalysis, electronics
and energy. Presently, for molybdenum disulfide, a promising catalyst for
artificial photosynthesis, considerable debate surrounds the structure/property
relationships of its various allotropes. Here we unambiguously solve the
structure of molybdenum disulfide monolayers using high-resolution transmission
electron microscopy supported by density functional theory and show lithium
intercalation to direct a preferential transformation of the basal plane from 2H
(trigonal prismatic) to 1T' (clustered Mo). These changes alter the energetics of
molybdenum disulfide interactions with hydrogen (DeltaG(H)), and, with respect to
catalysis, the 1T' transformation renders the normally inert basal plane amenable
towards hydrogen adsorption and hydrogen evolution. Indeed, we show basal plane
activation of 1T' molybdenum disulfide and a lowering of DeltaG(H) from +1.6 eV
for 2H to +0.18 eV for 1T', comparable to 2H molybdenum disulfide edges on
Au(111), one of the most active hydrogen evolution catalysts known.
PMID- 26442961
TI - Differential roles of dopamine D1 and D2 receptor-containing neurons of the
nucleus accumbens shell in behavioral sensitization.
AB - The nucleus accumbens (Nac) mediates the reinforcing and motor stimulating
properties of psychostimulants. It receives dopaminergic afferents from the
ventral midbrain and is divided into two distinct subregions: shell and core.
Each of these contains two subtypes of medium spiny neurons, which express either
dopamine D1 (D1R) or D2 (D2R) receptors. However, functional dissociation between
the two subtypes in psychostimulant response remains to be elucidated. We
performed selective ablation of each subtype in the Nac shell in mice, using
immunotoxin-mediated cell targeting, and examined the behavioral sensitization
evoked by repeated administration of methamphetamine. The D1R cell-ablated mice
exhibited delayed induction of sensitized locomotion compared to control mice,
whereas the D2R cell-ablated mice showed a mildly enhanced rate of induction of
sensitization. In vivo microdialysis revealed a marked blockade of the increase
in extracellular dopamine in the Nac of the D1R cell-ablated animals in response
to methamphetamine, indicating that the observed delay in behavioral
sensitization in these mice involves an impairment in accumbal dopamine release.
Our results reveal differential roles of D1R- and D2R-containing accumbal shell
neurons in the development of behavioral sensitization to psychostimulants.
Behavioral sensitization, enhanced motility by repetitive psychostimulant
administration, is a model of drug addiction. Here, we show that the nucleus
accumbens (Nac) shell neurons containing dopamine D1 receptor (D1R) or D2
receptor (D2R) play distinct roles in behavioral sensitization triggered by
methamphetamine, and that D1R-containing neurons enhance the induction of
behavioral sensitization at the early phase, whereas D2R-containing neurons act
to suppress the rate of development of the behavior.
PMID- 26442962
TI - Monitoring breast tumor progression by photoacoustic measurements: a xenograft
mice model study.
AB - The current study reports the photoacoustic spectroscopy-based assessment of
breast tumor progression in a nude mice xenograft model. The tumor was induced
through subcutaneous injection of MCF-7 cells in female nude mice and was
monitored for 20 days until the tumor volume reached 1000 mm3. The tumor tissues
were extracted at three different time points (days 10, 15, and 20) after tumor
inoculation and subjected to photoacoustic spectral recordings in time domain ex
vivo at 281 nm pulsed laser excitations. The spectra were converted into the
frequency domain using the fast Fourier transformed tools of MATLAB(r) algorithms
and further utilized to extract seven statistical features (mean, median, area
under the curve, variance and standard deviation, skewness and kurtosis) from
each time point sample to assess the tumor growth with wavelet principal
component analysis based logistic regression analysis performed on the data. The
prediction accuracies of the analysis for day 10 versus day 15, day 15 versus day
20, and day 10 versus day 20 were found to be 92.31, 87.5, and 95.2%,
respectively. Also, receiver operator characteristics area under the curve
analysis for day 10 versus day 15, day 15 versus day 20, and day 10 versus day 20
were found to be 0.95, 0.85, and 0.93, respectively. The ability of photoacoustic
measurements in the objective assessment of tumor progression has been clearly
demonstrated, indicating its clinical potential.
PMID- 26442963
TI - Laser line illumination scheme allowing the reduction of background signal and
the correction of absorption heterogeneities effects for fluorescence reflectance
imaging.
AB - Intraoperative fluorescence imaging in reflectance geometry is an attractive
imaging modality as it allows to noninvasively monitor the fluorescence targeted
tumors located below the tissue surface. Some drawbacks of this technique are the
background fluorescence decreasing the contrast and absorption heterogeneities
leading to misinterpretations concerning fluorescence concentrations. We propose
a correction technique based on a laser line scanning illumination scheme. We
scan the medium with the laser line and acquire, at each position of the line,
both fluorescence and excitation images. We then use the finding that there is a
relationship between the excitation intensity profile and the background
fluorescence one to predict the amount of signal to subtract from the
fluorescence images to get a better contrast. As the light absorption information
is contained both in fluorescence and excitation images, this method also permits
us to correct the effects of absorption heterogeneities. This technique has been
validated on simulations and experimentally. Fluorescent inclusions are observed
in several configurations at depths ranging from 1 mm to 1 cm. Results obtained
with this technique are compared with those obtained with a classical wide-field
detection scheme for contrast enhancement and with the fluorescence by an
excitation ratio approach for absorption correction.
PMID- 26442965
TI - Atrial myxomas and different clinical presentations.
PMID- 26442964
TI - ScbR- and ScbR2-mediated signal transduction networks coordinate complex
physiological responses in Streptomyces coelicolor.
AB - In model organism Streptomyces coelicolor, gamma-butyrolactones (GBLs) and
antibiotics were recognized as signalling molecules playing fundamental roles in
intra- and interspecies communications. To dissect the GBL and antibiotic
signalling networks systematically, the in vivo targets of their respective
receptors ScbR and ScbR2 were identified on a genome scale by ChIP-seq. These
identified targets encompass many that are known to play important roles in
diverse cellular processes (e.g. gap1, pyk2, afsK, nagE2, cdaR, cprA, cprB,
absA1, actII-orf4, redZ, atrA, rpsL and sigR), and they formed regulatory
cascades, sub-networks and feedforward loops to elaborately control key
metabolite processes, including primary and secondary metabolism, morphological
differentiation and stress response. Moreover, interplay among ScbR, ScbR2 and
other regulators revealed intricate cross talks between signalling pathways
triggered by GBLs, antibiotics, nutrient availability and stress. Our work
provides a global view on the specific responses that could be triggered by GBL
and antibiotic signals in S. coelicolor, among which the main echo was the change
of production profile of endogenous antibiotics and antibiotic signals manifested
a role to enhance bacterial stress tolerance as well, shedding new light on GBL
and antibiotic signalling networks widespread among streptomycetes.
PMID- 26442966
TI - Social Influence on Adolescent Polysubstance Use: The Escalation to Opioid Use.
AB - BACKGROUND: Fewer than 9% of 12-17 year olds in need (~146,000 of 1.7 million)
receive inpatient or outpatient substance abuse recovery services or other mental
health services (SAMHSA, 2012). The literature on adolescent addiction is sparse,
however, as most published addiction recovery efforts involve adult populations
often college students. OBJECTIVES: The present study examined social influences
on escalating substance use (from tobacco, alcohol, and marijuana use to
polysubstance use involving opioids) for students enrolled in recovery high
schools. METHODS: A sample of 31 adolescents enrolled in substance use recovery
high schools were surveyed on their patterns of substance use leading to their
abuse of opioids. RESULTS: Youth who begin their substance use as young as age 8
are often pressured by peer culture to do so and come from substance-using
families. Their escalation in polysubstance use to a pattern including opioids
was also most often attributed to peer influence over several years.
Conclusions/Importance: This paper is one of scant few that address patterns of
use in high school students. Perhaps most salient from this study are the
tertiary prevention implications: similar to their adult counterparts, students
enrolled in recovery high school programs are likely from substance-using
families and have combined complex constellations of substances including opioids
by dint of their relationships with substance-using peers.
PMID- 26442968
TI - Formation of oligopeptides in high yield under simple programmable conditions.
AB - Many high-yielding reactions for forming peptide bonds have been developed but
these are complex, requiring activated amino-acid precursors and heterogeneous
supports. Herein we demonstrate the programmable one-pot dehydration-hydration
condensation of amino acids forming oligopeptide chains in around 50% yield. A
digital recursive reactor system was developed to investigate this process,
performing these reactions with control over parameters such as temperature,
number of cycles, cycle duration, initial monomer concentration and initial pH.
Glycine oligopeptides up to 20 amino acids long were formed with very high
monomer-to-oligomer conversion, and the majority of these products comprised
three amino acid residues or more. Having established the formation of glycine
homo-oligopeptides, we then demonstrated the co-condensation of glycine with
eight other amino acids (Ala, Asp, Glu, His, Lys, Pro, Thr and Val),
incorporating a range of side-chain functionality.
PMID- 26442967
TI - A PI3K p110beta-Rac signalling loop mediates Pten-loss-induced perturbation of
haematopoiesis and leukaemogenesis.
AB - The tumour suppressor PTEN, which antagonizes PI3K signalling, is frequently
inactivated in haematologic malignancies. In mice, deletion of PTEN in
haematopoietic stem cells (HSCs) causes perturbed haematopoiesis,
myeloproliferative neoplasia (MPN) and leukaemia. Although the roles of the PI3K
isoforms have been studied in PTEN-deficient tumours, their individual roles in
PTEN-deficient HSCs are unknown. Here we show that when we delete PTEN in HSCs
using the Mx1-Cre system, p110beta ablation prevents MPN, improves HSC function
and suppresses leukaemia initiation. Pharmacologic inhibition of p110beta in PTEN
deficient mice recapitulates these genetic findings, but suggests involvement of
both Akt-dependent and -independent pathways. Further investigation reveals that
a p110beta-Rac signalling loop plays a critical role in PTEN-deficient HSCs.
Together, these data suggest that myeloid neoplasia driven by PTEN loss is
dependent on p110beta via p110beta-Rac-positive-feedback loop, and that
disruption of this loop may offer a new and effective therapeutic strategy for
PTEN-deficient leukaemia.
PMID- 26442969
TI - Oxidative Self-Polymerization of Dopamine in an Acidic Environment.
AB - A weak alkaline condition (pH > 8) is a general requirement for oxidative self
polymerization of dopamine. Here, we first demonstrated the generation of
polydopamine in an acidic environment via a hydrothermal method. The pH scope of
self-polymerization of dopamine is extended to pH ~ 1 in a hydrothermal process.
Polydopamine generated via a hydrothermal method shows similar chemical features
and radical scavenging activity with that generated in a basic environment.
PMID- 26442970
TI - A phase II study of nab-paclitaxel plus carboplatin in combination with thoracic
radiation in patients with locally advanced non-small-cell lung cancer.
AB - We investigated the efficacy and safety of albumin-bound paclitaxel (nab-PTX) and
carboplatin (CBDCA) with concurrent radiotherapy for unresectable locally
advanced non-small-cell lung cancer (NSCLC). Patients with Stage III NSCLC and an
Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible.
Concurrent chemoradiotherapy consisted of weekly administration of nab-PTX (40
mg/m(2)) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and
thoracic radiotherapy (60 Gy/30 fractions) for a total of 6 weeks. After
concurrent chemoradiotherapy, patients received an additional two cycles of
consolidation phase chemotherapy that consisted of 4-week cycles of nab-PTX (100
mg/m(2) on Days 1, 8 and 15)/CBDCA (AUC 5 mg/ml/min on Day 1). Response was
evaluated in accordance with the Response Evaluation Criteria in Solid Tumors.
Progression-free survival and overall survival were estimated using the Kaplan
Meier method. Toxicity was graded using the National Cancer Institute Common
Terminology Criteria for Adverse Events. A total of 10 patients were enrolled in
this trial between September 2013 and January 2014 from three institutes. The
overall response rate was 40.0% and the median progression-free survival was 6.7
months. Treatment-related death occurred in two patients. Grade 2 or worse severe
radiation pneumonitis was observed in all three patients that had the volume of
lung receiving at least 20 Gy (V20) >30%. The results of this study indicate that
no further investigation is warranted into nab-PTX and CBDCA with concurrent
thoracic radiation for Stage III NSCLC with V20 > 30% due to severe toxicity.
PMID- 26442971
TI - Economic and Social Impact of Increasing Uptake of Cardiac Rehabilitation
Services--A Cost Benefit Analysis.
AB - BACKGROUND: Cardiac rehabilitation can reduce mortality, improve cardiac risk
factor profile and reduce readmissions; yet uptake remains low at 30%. This
research aims to investigate the social and economic impact of increasing the
uptake of cardiac rehabilitation in Victoria, Australia using cost benefit
analysis (CBA). METHODS: Cost benefit analysis has been undertaken over a 10-year
period to analyse three scenarios: (1) Base Case: 30% uptake; (2) Scenario 1: 50%
uptake; and (3) Scenario 2: 65% uptake. Impacts considered include cardiac
rehabilitation program costs, direct inpatient costs, other healthcare costs,
burden of disease, productivity losses, informal care costs and net deadweight
loss. RESULTS: There is a net financial saving of $46.7-$86.7 million under the
scenarios. Compared to the Base Case, an additional net benefit of $138.9-$227.2
million is expected. This results in a Benefit Cost Ratio of 5.6 and 6.8 for
Scenarios 1 and 2 respectively. Disability Adjusted Life Years were 21,117-37,565
years lower than the Base Case. CONCLUSIONS: Greater uptake of cardiac
rehabilitation can reduce the burden of disease, directly translating to benefits
for society and the economy. This research supports the need for greater
promotion, routine referral to be made standard practice and implementation of
reforms to boost uptake.
PMID- 26442973
TI - [Choosing the right medications in elderly patients with chronic kidney disease].
AB - With the aging of the population, the prevalence of chronic kidney disease (CKD)
is increased. Measurement of glomerular filtration rate as a screening tool may
over-diagnose CKD, especially when proteinuria is normal, but it can be very
useful when considering drug metabolism. Renal dysfunction is a factor
predisposing to potential adverse drug reactions, because drug can accumulate to
toxic levels. In addition, some drugs are nephrotoxic and can more easily damage
the kidneys in the elderly. Limited data are available on the risks of drugs in
the elderly population with CKD. Drugs with no clear evidence-based indication,
drugs with higher risks of adverse side effects compared to their benefits, and
drugs which are not cost-effective, have been defined "potentially inappropriate
medications" (PIMs). Even if criteria to evaluate PIMs and adverse drug reactions
are available to clinical management, we strongly support the idea that the issue
of PIMs in the elderly affected by CKD should be better studied and defined. The
Italian website Slow Medicine, based on the US project "Choosing Wisely", opened
a new strategy in this field, taking into consideration both economic issues and
patients quality of life. The main goal of this initiative is avoiding wasteful
or unnecessary medical tests, treatments and procedures.
PMID- 26442974
TI - [Advance directives in Italy: a goal not yet reached but already passed?].
AB - The advance directives (ADs) have been adopted in many countries to defend
patients' autonomy. In Italy, in the past, this topic gave rise to a heated
debate involving philosophers, theologians, and politicians. In 2009, the
government presented a bill of law on ADs firmly criticized from a scientific,
moral and juridical point of view because the bill's content is against the
principles of Italian Constitution, Italian Code of Medical Ethics, Oviedo
Convention, and official statements of many scientific societies. Although the
bill has passed the Low Chamber it lies, even since, in the Senate, lacking in
regard any agreement among the political parties. The purpose of this article is
to highlight that, in our country, patients, relatives and doctors deserve a law
not only related to the specific topic of ADs, but - as in other European
countries (Germany, Spain, France, UK) - aimed to deal with the complex issue of
end of life care as a whole. This law should take into account the sound evidence
existing in regard to the four fundamental principles supporting the best
scientific and ethical approaches to the end of life issues: shared decision
making process between doctors and patients/relatives; rejection of dying process
marked by the suffering; withholding/withdrawing futile treatments together with
palliative sedation as two crucial contributions to suppress the patient
suffering and pain; clear-cut difference between these clinical/ethical options
and euthanasia. At the same time, this law should be able to provide physicians
with a legal coverage to make all the clinical and ethical decisions more and
more complex because of the continuous evolution of medical science on one hand,
and the impressive development of biotechnology on the other hand.
PMID- 26442975
TI - [Clinical research evolution. In parallel with the current changes in welfare
expectations and information technology incorporation, study designs and data
collection and analysis are quickly changing as well].
AB - The development of both technology, biological, and clinical knowledge leads to
remarkable changes of scientific research methodology, including the clinical
research. Major changes deal with the pragmatic approach of trial designs, an
explosive diffusion of observational research which is becoming a usual component
of clinical practice, and an active modelling of new research design. Moreover, a
new healthcare landscape could be generated from the information technology
routinely used to collect clinical data in huge databases, the management and the
analytic methodology of big data, and the development of biological sensors
compatible with the daily life delivering signals remotely forwardable to central
databases. Precision medicine and individualized medicine seem to be the big
novelties of the coming years, guiding to a shared pattern of patient/physician
relationship. In healthcare, a huge business related mainly, but not exclusively,
to the implementation of information technology is growing. This development will
favor radical changes in the health systems, also reshaping the clinical
activity. A new governance of the research strategies is needed and the
application of the results should be based on shared ethical foundations. This
new evolving profile of medical research and practice is discussed in this paper.
PMID- 26442976
TI - [Treatment of acute coronary syndrome in older adults and high-risk
patients."When the going gets tough..."].
AB - The increasing life expectancy in older adults and the better survival of
patients with multiple pathologies require the capability to treat complex
clinical conditions with an increased risk of iatrogenic complications.
Nevertheless, recent improvements in the pharmacological and interventional
treatment of acute coronary syndrome (ACS) have promoted a shift from therapeutic
nihilism to a more active management of complex ACS cases. Despite the paucity of
specific randomized clinical trials, observational studies seem to show benefit
of an early invasive treatment in these patients. This approach requires close
cooperation of clinical intensivists, interventional cardiologists and
cardiovascular surgeons either in a specialized heart center or in a network of
hospitals.
PMID- 26442977
TI - [Well ageing in the XXI century. Political, social and individual strategies].
AB - Population ageing is a triumph, but because to the tendency to the increase of
the phenomenon in all countries of the globe, it is also a concern and a
challenge for national governments and societies. Starting from the current
picture in the States of European Union and the future predictions, it's provides
an overview of the relationship between ageing and health, emphasizing some
social, political and person-related aspects. In particular, it's examined the
theoretical models, strategies and multilevel actions proposed to well-ageing and
with dignity, focusing on the model of "active and healthy ageing" promoted in
2012 by the World Health Organization and the European Union.
PMID- 26442979
TI - [In Process Citation].
PMID- 26442978
TI - [Direct and indirect costs associated with respiratory allergic diseases in
Italy. A probabilistic cost of illness study].
AB - BACKGROUND: The respiratory allergies, including allergic rhinitis and allergic
asthma, represent a substantial medical and economic burden worldwide. Despite
their dimension and huge economic-social burden, no data are available on the
costs associated with the management of respiratory allergic diseases in Italy.
The objective of this study was to estimate the average annual cost incurred by
the National Health Service (NHS), as well as society, due to respiratory
allergies and their main co-morbidities in Italy. METHODS: A probabilistic
prevalence-based cost of illness model was developed to estimate an aggregate
measure of the economic burden associated with respiratory allergies and their
main co-morbidities in terms of direct and indirect costs. A systematic
literature review was performed in order to identify both the cost per case
(expressed in present value) and the number of affected patients, by applying an
incidence-based estimation method. Direct costs were estimated multiplying the
hospitalization, drugs and management costs derived by the literature with the
Italian epidemiological data. Indirect costs were calculated based on lost
productivity according to the human capital approach. Furthermore, a one-way and
probabilistic sensitivity analysis with 5,000 Monte Carlo simulations were
performed, in order to test the robustness of the results and define the proper
95% Confidence Interval (CI). RESULTS: Overall, the total economic burden
associated with respiratory allergies and their main co-morbidities was ? 7.33
billion (95% CI: ? 5.99-? 8.82). A percentage of 27.5% was associated with
indirect costs (? 2.02; 95% CI: ? 1.72-? 2.34 billion) and 72.5% with direct
costs (? 5.32; 95% CI: ? 4.04-? 6.77 billion). In allergic asthma, allergic
rhinitis, combined allergic rhinitis and asthma, turbinate hypertrophy and
allergic conjunctivitis, the model estimate an average annual economic burden of
? 1,35 (95% CI: ? 1,14-? 1,58) billion, ? 1,72 (95% CI: ? 1,14-? 2,43) billion, ?
1,62 billion (? 0,91-? 2,53) billion, ? 0,12 (? 0,07-? 0,17) billion, ? 0,46 (?
0,16-? 0,92) billion respectively. CONCLUSIONS: To our knowledge, this is the
first study in which direct costs (incurred by NHS) and indirect ones (incurred
by the society) were taken into account to estimate the overall burden associated
with respiratory allergies and their main co-morbidities in our Country. In
conclusion, this work may be considered an efficient tool for public decision
makers to correctly understand the economic aspects involved by the management
and treatment of respiratory allergies-induced diseases in Italy.
PMID- 26442980
TI - [In Process Citation].
PMID- 26442982
TI - Effect of respiratory protector intervention among indium reclaiming workers.
PMID- 26442981
TI - Stabilization of SIRT7 deacetylase by viral oncoprotein HBx leads to inhibition
of growth restrictive RPS7 gene and facilitates cellular transformation.
AB - Sirtuin-7 (SIRT7) deacetylase exhibits a high selectivity for acetylated H3K18
and has been implicated in the maintenance of malignant phenotype. However, it
remains unclear if SIRT7 and H3K18ac play a role in the tumorigenic program
driven by oncogenic viruses. We show that ectopically expressed HBx oncoprotein
of hepatitis B virus promoted intracellular stability of SIRT7 by salvaging it
from ubiquitin-mediated proteasomal degradation. HBx-dependent accumulation of
SIRT7 favored H3K18 deacetylation and down-regulated the small ribosomal protein
gene, RPS7, involved in cell death and DNA damage response. HBx facilitated the
recruitment of SIRT7 to RPS7 promoter thus impeding H3K18ac occupancy and
hindering RPS7 transcription. The antagonistic relationship between SIRT7 and
RPS7 was also observed in the HBx transgenic mice, where elevated levels of SIRT7
protein were coincident with low levels of H3K18ac and RPS7. Strikingly,
inhibition of cellular deubiquitinase activity restored RPS7 gene transcription.
Further, depletion of endogenous SIRT7 led to decreased cell viability and
transformation. The biological relevance of RPS7 suppression by HBx-SIRT7 axis
was evident from ectopic expression of RPS7 which attenuated clonogenicity of
cells. Thus, our findings suggest that SIRT7 is a critical regulator of HBx
driven oncogenic program, through its antagonistic impact on growth restrictive
ribosomal protein RPS7.
PMID- 26442983
TI - Investigating the adduct formation of organic mercury species with carbonic
anhydrase and hemoglobin from human red blood cell hemolysate by means of LC/ESI
TOF-MS and LC/ICP-MS.
AB - The interaction of mercury species with human erythrocytes is studied to
investigate possible high molecular binding partners for mercury species. Human
blood hemolysate was spiked with methylmercury and investigated by means of
liquid chromatography (LC) coupled to electrospray ionization time of flight mass
spectrometry (ESI-ToF-MS) and inductively coupled plasma mass spectrometry (ICP
MS). Beside adduct formation of mercury species with hemoglobin, the main
compound of the erythrocytes, mercury binding to the enzyme carbonic anhydrase
was revealed. Due to an enzymatic digest of the protein-mercury adduct, the
binding site at the free thiol group of the protein was identified. These results
indicate that carbonic anhydrase might play a role in mercury toxicity.
PMID- 26442984
TI - Individualised Versus Standardised Assessment of Quality of Life in Eating
Disorders.
AB - Individualised measures of quality of life (QoL) refer to instruments that
encourage the respondent to actively elicit which areas of their life are most
relevant for his/her QoL. The aim of this study is to compare individualised
versus standard measures of QoL in a sample of patients with eating disorder
(ED). The Schedule for the Evaluation of the Individual Quality of Life (SEIQoL)
and a generic measure of QoL [World Health Organization Brief Quality of Life
Assessment Scale (WHOQOL-BREF)] were applied on two occasions (one-year follow
up) to a sample of 165 patients with ED, 57 recovered patients with ED, and 349
women from the general population. The areas of 'family', 'education/career or
job', 'friends', 'leisure', 'romantic partner' and 'health' were identified as
the most important for their QoL for all groups, both times. The WHOQOL-BREF was
more sensitive than the SEIQoL in detecting changes that occurred over time.
Clinical interventions for ED should consider social components as objectives of
intervention.
PMID- 26442985
TI - Greater support and debriefing may help student midwives to process traumatic
birth experiences.
PMID- 26442986
TI - Efficient Generation of Gene-Modified Pigs Harboring Precise Orthologous Human
Mutation via CRISPR/Cas9-Induced Homology-Directed Repair in Zygotes.
AB - Precise genetic mutation of model animals is highly valuable for functional
investigation of human mutations. Clustered regularly interspaced short
palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-induced homology-directed
repair (HDR) is usually used for precise genetic mutation, being limited by the
relatively low efficiency compared with that of non-homologous end joining
(NHEJ). Although inhibition of NHEJ was shown to enhance HDR-derived mutation, in
this work, without inhibition of NHEJ, we first generated gene-modified pigs
harboring precise orthologous human mutation (Sox10 c.A325>T) via CRISPR/Cas9
induced HDR in zygotes using single-strand oligo DNA (ssODN) as template with an
efficiency as high as 80%, indicating that pig zygotes exhibited high activities
of HDR relative to NHEJ and were highly amendable to genetic mutation via
CIRSPR/Cas9-induced HDR. Besides, we found a higher concentration of ssODN
remarkably reduced HDR-derived mutation in pig zygotes, suggesting a possible
balance for optimal HDR-derived mutation in zygotes between the excessive
accessibility to HDR templates and the activities of HDR relative to NHEJ which
appeared to be negatively correlated to ssODN concentration. In addition, the HDR
derived mutation, as well as those from NHEJ, extensively integrated into various
tissues including gonad of founder pig without detected off-targeting, suggesting
CRISPR/Cas9-induced HDR in zygotes is a reliable approach for precise genetic
mutation in pigs.
PMID- 26442987
TI - Asian Indians in America: The influence of values and culture on mental health.
AB - Asian Indians represent a significant portion of the largest growing race of
Asians in the past decade in the United States. This selective review examines
major cultural themes related to first- and second-generation Asian Indians
living in the United States as they impact psychological and psychiatric
dysfunction in this population. Specifically, we review the impact of Asian
Indian culture on mental health, discuss the impact of acculturation and ethnic
identity development on the mental health of Indian-Americans, and focus on
typical mental health problems of Asian Indian adolescents, women and elderly in
America. Finally, we provide a brief overview of empirically-supported treatment
approaches and cultural considerations for additional treatments relevant to this
population. This review is intended to provide an important foundation for more
systematic empirically-driven investigation into better understanding how Asian
Indian cultural themes impact mental health for Indian-Americans, and how to
develop effective treatments for these issues in this cultural group.
PMID- 26442988
TI - Reliability, validity and factor structure of the CES-D in Iranian elderly.
AB - OBJECTIVES: In developing countries such as Iran, elder populations are growing.
Due to the high prevalence of depressive disorders among elders, reliable
screening instruments for this population are required. The main purpose of this
study was to determine the reliability and validity of the Farsi version of the
Center for Epidemiological Studies-Depression Scale-10 (CES-D) among Iranian
elderly persons. METHODS: The investigators created the Farsi version of the CES
D-10 by translation and back translation. Two hundred and four cases aged 59 and
above completed the questionnaire. The reliability and validity of the translated
CES-D-10 was established through comparison with the Composite International
Diagnostic Interview (CIDI), a recognized gold standard method for diagnosing
major depressive disorder. We used a receiver operating curve (ROC) to determine
the optimum cutoff score. RESULTS: The Farsi version of the CED-D-10 displayed
acceptable psychometric characteristics, as reflected in internal consistency
with Cronbach's alpha, split-half coefficients and test-retest reliability of
0.85, 0.65 and 0.49, respectively. Factor analysis and the varimax rotation
resulted in two factors including 'depression' and 'interpersonal relationships'.
The Depression factor (introduced as CES-D-8 of the scale) had significant
correlation with the 10 items form (r=0.99) with 0.87 alpha coefficient. The ROC
showed that the optimum cutoff point is 5 with sensitivity of 82% and specificity
of 70%, and positive and negative predictive values of 26% and 98%, respectively,
for both of the forms. CONCLUSION: Both the 10 and 8 items form of the Farsi
version have desirable characteristics to be useful as a screening instrument for
depressive disorders in Iranian elders, especially in urban areas.
PMID- 26442989
TI - Reflections on attitudes, experiences, and vulnerability of intimate partner
violence among Southeast Asian college women living in United States.
AB - To provide culturally sensitive intimate partner violence (IPV) prevention
programs for ethnic groups, a basic foundational understanding of Southeast Asian
(SEA) women living in the United States is vital. The purpose of this study was
to describe SEA college women's perceptions of IPV and how the women recognize
their vulnerability to such violent situations. Qualitative methods using focus
group discussions were employed to elicit participants' perceptions. Participants
included 18 SEA college women, ages 18-34 (Mean=22; SD=7.22). Transcriptions were
analyzed using a content analysis approach. Five themes emerged: recognition of
IPV; perception of individual vulnerability to IPV; experience and responses to
IPV; help seeking and support system; and strategies used for prevention of IPV.
Findings yielded an understanding of intertwined issues of cultural norms
associated with IPV, social and economic disparities, and challenges for IPV
prevention in SEA communities. Culturally sensitive prevention programs will be
more effective by reforming cultural values, while at the same time promoting non
violent relationships and increasing access to services.
PMID- 26442990
TI - Flavisolibacter ginsenosidimutans sp. nov., with ginsenoside-converting activity
isolated from soil used for cultivating ginseng.
AB - A Gram-reaction-negative, aerobic, non-motile and rod-shaped bacterial strain
designated Gsoil 636T was isolated from soil of a ginseng cultivation field in
Pocheon Province, South Korea and its taxonomic position was investigated using a
polyphasic approach. Gsoil 636T grew at 18-30 degrees C and at pH 6.0-8.0 on R2A
medium. Gsoil 636T possessed beta-glucosidase activity, which was responsible for
its ability to transform ginsenoside Rb1 (ones of the dominant active components
of ginseng) to F2. On the basis of 16S rRNA gene sequence similarity, Gsoil 636T
was shown to belong to the family Chitinophagaceae and to be related to
Flavisolibacter ginsengiterrae Gsoil 492T (96.7 % sequence similarity),
Flavisolibacter ginsengisoli Gsoil 643T (96.6 %) and Flavisolibacter rigui
02SUJ3T (96.6 %). The G+C content of the genomic DNA was 48.9 %. The predominant
respiratory quinone was MK-7 and the major fatty acids were iso-C15 : 0, summed
feature 3 (comprising C16 : 1omega6c and/or C16 : 1omega7c) and iso-C17 : 0 3-OH.
DNA and chemotaxonomic data supported the affiliation of Gsoil 636T to the genus
Flavisolibacter. Gsoil 636T could be differentiated genotypically and
phenotypically from the species of the genus Flavisolibacter with validly
published names. The isolate therefore represents a novel species, for which the
name Flavisolibacter ginsenosidimutans sp. nov. is proposed, with the type strain
Gsoil 636T (KCTC 22818T = JCM 18197T = KACC 14277T).
PMID- 26442991
TI - Severe Headache With Left Nasal Discharge: Is it Always Due to Autonomic Over
Activity?
PMID- 26442992
TI - Exposure to graphic warning labels on cigarette packages: Effects on implicit and
explicit attitudes towards smoking among young adults.
AB - OBJECTIVE: To test the effect of exposure to the US Food and Drug
Administration's proposed graphic images with text warning statements for
cigarette packages on implicit and explicit attitudes towards smoking. DESIGN AND
METHODS: A two-session web-based study was conducted with 2192 young adults 18-25
years-old. During session one, demographics, smoking behaviour, and baseline
implicit and explicit attitudes were assessed. Session two, completed on average
18 days later, contained random assignment to viewing one of three sets of
cigarette packages, graphic images with text warnings, text warnings only, or
current US Surgeon General's text warnings. Participants then completed post
exposure measures of implicit and explicit attitudes. ANCOVAs tested the effect
of condition on the outcomes, controlling for baseline attitudes. RESULTS:
Smokers who viewed packages with graphic images plus text warnings demonstrated
more negative implicit attitudes compared to smokers in the other conditions (p =
.004). For the entire sample, explicit attitudes were more negative for those who
viewed graphic images plus text warnings compared to those who viewed current US
Surgeon General's text warnings (p = .014), but there was no difference compared
to those who viewed text-only warnings. CONCLUSION: Graphic health warnings on
cigarette packages can influence young adult smokers' implicit attitudes towards
smoking.
PMID- 26442993
TI - Reduction in Abeta-induced cell death in the hippocampus of 17beta-estradiol
treated female rats is associated with an increase in IGF-I signaling and
somatostatinergic tone.
AB - Several studies indicate that 17beta-estradiol (E2) protects against amyloid beta
peptide (Abeta)-induced cell death and activates factors associated with learning
and memory, a function involving the hippocampal somatostatinergic system. As
alterations in somatostatin have been demonstrated in Alzheimer's disease, we
examined whether E2 prevents changes in the hippocampal somatostatinergic system
induced by Abeta25-35 and cell death, as well as the possible involvement of
leptin and insulin-like growth factor (IGF)-I signaling. We also measured the
levels of Abeta proteases neprilysin and insulin-degrading-enzyme. Co
administration of E2 with Abeta25-35 reduced both its levels and cell death, in
addition to preventing the Abeta-induced depletion of some somatostatinergic
parameters. Activation of leptin and IGF-I pathways increased after E2 co
administration, and this correlated with changes in the somatostatinergic system.
Changes in some components of this system were inversely related with Abeta
levels and cell death. Moreover, neprilysin levels were increased only in Abeta
plus E2-treated rats and E2 prevented the Abeta-induced insulin-degrading-enzyme
reduction. Our results suggest that the E2-induced reduction in cell death is
related to lower Abeta levels, probably because of IGF-I and somatostatin
modulation of Abeta proteases. We asked how 17beta-estradiol (E2) protects
against beta-amyloid (Abeta)-induced cell death. E2 co-administration prevents
Abeta-produced depletion of hippocampal somatostatin (SRIF) by an IGF-I-mediated
mechanism, being related this protective effect with an increase in Abeta
proteases. Our results suggest that the E2-induced reduction in cell death is
related to lower Abeta levels, probably because of SRIF modulation of Abeta
proteases. CREB, cAMP response element-binding protein; IGF-I, insulin-like
growth factor-I; STAT3, signal transducer and activator of transcription-3.
PMID- 26442994
TI - Investigation of the magnetic properties in double perovskite R2CoMnO6 single
crystals (R = rare earth: La to Lu).
AB - We have successfully synthesized the series of the double-perovskite R2CoMnO6 (R
= rare earth: La to Lu) single crystals and have investigated their magnetic
properties. The ferromagnetic order of Co(2+)/Mn(4+) spins emerges mainly along
the c axis. Upon decreasing the size of rare earth ion, the magnetic transition
temperature decreases linearly from 204 K for La2CoMnO6 to 48 K for Lu2CoMnO6,
along with the enhancement of monoclinic distortion. The temperature and magnetic
field dependences of magnetization reveal the various magnetic characteristics
such as the metamagnetic transition in R = Eu, the isotropic nature of rare
earth moment in R = Gd, and the reversal of magnetic anisotropy in R = Tb and
Dy. Our results offer comprehensive information for understanding the roles of
mixed-valent magnetic ions and rare earth magnetic moments on the magnetic
properties.
PMID- 26442995
TI - Fusion with pep-1, a cell-penetrating peptide, enhances the transmembrane ability
of human epidermal growth factor.
AB - Administration of macromolecule compositions in medicine and cosmetics always
exhibited low bioavailability due to the limitation of transmembrane transport.
Here, human epidermal growth factor (hEGF) was fused with glutathione S
transferase (GST) and Pep-1, the first commercial cell-penetrating peptide, in
Escherichia coli. The fusion protein was firstly purified with the affinity
chromatography, and then the GST tag was released by TEV protease. Final
purification was achieved by the ion exchange chromatography. The biological
activities and the transmembrane ability of the obtained products were determined
using scratch wound-healing assay, MTT analysis, and immunofluorescence assay.
The results showed that both rhEGF and Pep-1-fused hEGF were soluble expressed in
E. coli. The fusion of Pep-1 could markedly increase the transmembrane ability of
EGF, whereas it did not interfere with the growth-stimulating and migration
promoting functions of hEGF on fibroblasts. This research provided a novel
strategy for the transmembrane transport of protein-derived cosmetics or drugs.
PMID- 26442997
TI - Curcumin enhances the activity of fluconazole against Cryptococcus gattii-induced
cryptococcosis infection in mice.
AB - AIM: The aim of this study was to investigate the in vitro and in vivo activities
of pure curcumin, as well as its combination with fluconazole, against
Cryptococcus gattii. METHODS AND RESULTS: The minimal inhibitory concentrations
(MIC) of curcumin and its interactions with fluconazole against C. gattii were
assessed in vitro using standard methods. This same combination was used to treat
C. gattii-induced cryptococcosis in mice. The behavioural and functional
assessment of the mice during treatment was also performed. The average MIC for
curcumin was 19.8 MUg ml(-1) . Its combination with fluconazole resulted in
FICSigma (fractional inhibitory concentration index) values between 0.79 and
2.29. Curcumin (alone or combined with fluconazole) significantly reduced
pulmonary damage and fungal burden in the brain. No colonies were found in the
brain following combination treatment, which was also confirmed by the improved
behaviour of mice. CONCLUSIONS: The combination therapy with curcumin and
fluconazole was the most effective among the treatments tested, as in addition to
reducing the fungal burden and damage on lung tissues, it was able to eliminate
the fungal burden in the brain, enhancing the survival of mice. SIGNIFICANCE AND
IMPACT OF THE STUDY: This study points to the possibility of using curcumin in
combination with fluconazole as a clinical treatment of cryptococcosis.
PMID- 26442998
TI - Urinary 8-Hydroxy-2'-Deoxyguanosine: A Biomarker for Radiation-Induced Oxidative
DNA Damage in Pediatric Cardiac Catheterization.
AB - OBJECTIVE: To determine the utility of urinary 8-hydroxy-2'-deoxyguanosine (8
OHdG) as a sensitive biomarker for radiation-induced cellular DNA damage in
children undergoing cardiac catheterization. STUDY DESIGN: We enrolled pediatric
patients with congenital heart diseases requiring cardiac catheterization in
conjunction with healthy children and children under sedation as control.
Demographic, clinical, laboratory and invasive hemodynamic data, urinary 8-OHdG
levels, and radiation exposure measurements were collected prospectively.
RESULTS: Nineteen patients, 10 healthy children and 9 children under sedation,
were studied. In 19 patients who underwent cardiac catheterization, the median
level of 8-OHdG in urine obtained at 24-48 hours after the procedure was
significantly higher than at baseline (44.0 vs 17.3 ng/mg creatinine, P = .0001).
Furthermore, the urinary 8-OHdG level after the procedure increased in 18 of the
19 study subjects. In contrast, there was no significant difference in 8-OHdG
levels between the 2 spot urine samples obtained at arbitrary intervals of 24-48
hours in 10 healthy children (P = .7213), and at baseline and 24-48 hours
following echocardiography in 9 children under sedation (P = .1097). Stepwise
multiple regression analysis revealed that the cumulative air kerma during the
cardiac catheterization was the variable which was strongly and significantly
associated with the ratio of post- to precardiac catheterization urinary 8-OHdG
levels among the evaluated variables (R(2) = 0.7179, F = 11.0256, P = .0007).
CONCLUSIONS: Urinary 8-OHdG could be a useful biomarker for radiation-induced
cellular DNA damage in children undergoing diagnostic cardiac catheterization.
PMID- 26443000
TI - Reliable Hydrogel with Mechanical "Fuse Link" in an Aqueous Environment.
AB - A robust hydrogel with a reliable deformation region in an aqueous environment is
proposed. The gel has a homogeneous network where hydrophilic/hydrophobic
components are uniformly distributed. In an aqueous environment, aggregated
hydrophobic segments serve as "mechanical fuse links," inhibiting sudden
macroscopic fracture. The gel endures threefold stretching for more than 100
cycles in water without mechanical hysteresis.
PMID- 26442999
TI - Enzyme-linked DNA dendrimer nanosensors for acetylcholine.
AB - It is currently difficult to measure small dynamics of molecules in the brain
with high spatial and temporal resolution while connecting them to the bigger
picture of brain function. A step towards understanding the underlying neural
networks of the brain is the ability to sense discrete changes of acetylcholine
within a synapse. Here we show an efficient method for generating acetylcholine
detecting nanosensors based on DNA dendrimer scaffolds that incorporate
butyrylcholinesterase and fluorescein in a nanoscale arrangement. These
nanosensors are selective for acetylcholine and reversibly respond to levels of
acetylcholine in the neurophysiological range. This DNA dendrimer architecture
has the potential to overcome current obstacles to sensing in the synaptic
environment, including the nanoscale size constraints of the synapse and the
ability to quantify the spatio-temporal fluctuations of neurotransmitter release.
By combining the control of nanosensor architecture with the strategic placement
of fluorescent reporters and enzymes, this novel nanosensor platform can
facilitate the development of new selective imaging tools for neuroscience.
PMID- 26443001
TI - Synthesis, fungicidal activity and structure-activity relationships of 3-benzoyl
4-hydroxylcoumarin derivatives.
AB - BACKGROUND: To develop a coumarin-based fungicide, a series of 3-benzoyl-4
hydroxylcoumarin derivatives were synthesised and their fungicidal activities
were evaluated against typical fungi occurring in Chinese agroecosystems.
RESULTS: Target compounds were characterised through (1) H NMR, (13) C NMR and
high-resolution mass spectrometry. The crystal structure of compound III-21 was
determined through X-ray diffraction. Bioassay results indicated that most of the
target compounds showed good growth inhibition against all of the fungi tested in
vitro. EC50 of the target compounds against Physalospora piricola, Rhizoctonia
cerealis, Sclerotinia sclerotiorum and Botrytis cinerea indicated that most of
the target compounds displayed comparable activity with that of carbindazim and
chlorothalonil in vitro. Among these compounds, the analogue 3-(2-bromo-4
chlorobenzoyl)-4-hydroxylcoumarin (III-21) displayed the optimum growth
inhibition against R. cerealis (87.5%) and B. cinerea (82.7%) in vivo at 200 ug
mL(-1) concentration; thus, this analogue is a potential inhibitor of pathogenic
fungi and a new major compound for further optimisation. The results of analysing
the structure-activity relationships demonstrated that changes in substituents on
benzene ring A of 3-benzoyl-4-hydroxylcoumarin caused different fungicidal
activities and provided original information on the preferential conformation to
maintain high activities. CONCLUSION: The present work demonstrated that 3
benzoyl-4-hydroxylcoumarin derivatives can be used as possible major compounds to
develop novel fungicides. (c) 2015 Society of Chemical Industry.
PMID- 26443002
TI - Effect of music care on depression and behavioral problems in elderly people with
dementia in Taiwan: a quasi-experimental, longitudinal study.
AB - OBJECTIVES: The purpose was to examine the effectiveness of music care on
cognitive function, depression, and behavioral problems among elderly people with
dementia in long-term care facilities in Taiwan. METHODS: The study had a quasi
experimental, longitudinal research design and used two groups of subjects.
Subjects were not randomly assigned to experimental group (n = 90) or comparison
group (n = 56). Based on Bandura's social cognition theory, subjects in the
experimental group received Kagayashiki music care (KMC) twice per week for 24
weeks. Subjects in the comparison group were provided with activities as usual.
RESULTS: Results found, using the control score of the Clifton Assessment
Procedures for the Elderly Behavior Rating Scale (baseline) and time of attending
KMC activities as a covariate, the two groups of subjects had statistically
significant differences in the mini-mental state examination (MMSE). Results also
showed that, using the control score of the Cornell Scale for Depression in
Dementia (baseline) and MMSE (baseline) as a covariate, the two groups of
subjects had statistically significant differences in the Clifton Assessment
Procedures for the Elderly Behavior Rating Scale. CONCLUSION: These findings
provide information for staff caregivers in long-term care facilities to develop
a non-invasive care model for elderly people with dementia to deal with
depression, anxiety, and behavioral problems.
PMID- 26443003
TI - Vesicular trafficking mechanisms in endothelial cells as modulators of the tumor
vasculature and targets of antiangiogenic therapies.
AB - A common feature of solid tumors is their ability to incite the formation of new
blood and lymph vessels trough the processes of angiogenesis and
lymphangiogenesis, respectively, to support tumor growth and favor metastatic
dissemination. As a result of the lack of feedback regulatory control mechanisms
or due to the exacerbated presence of pro-angiogenic signals within the tumor
microenvironment, the tumor endothelium receives continuous signals to sprout and
develop, generating vessels that are structurally and functionally abnormal. An
emerging mechanism playing a central role in shaping the tumor vasculature is the
endothelial-vesicular network that regulates trafficking/export and degradation
of key signaling proteins and membrane receptors, including the vascular
endothelial growth-factor receptor-2/3 and members of the Notch pathway. Here we
will discuss recent evidence highlighting how vesicular trafficking mechanisms in
endothelial cells contribute to pathological angiogenesis/lymphangiogenesis and
can provide novel and exploitable targets in antiangiogenic therapies.
PMID- 26443004
TI - Interventions for hidradenitis suppurativa.
AB - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin
condition characterised by recurrent painful boils in flexural sites, such as the
axillae and groin, that affects about 1% of the population, with onset in early
adulthood. OBJECTIVES: To assess the effects of interventions for HS in people of
all ages. SEARCH METHODS: We searched the following databases up to 13 August
2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane
Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS
(from 1982). We also searched five trials registers and handsearched the
conference proceedings of eight dermatology meetings. We checked the reference
lists of included and excluded studies for further references to relevant trials.
SELECTION CRITERIA: Randomised controlled trials (RCTs) of all interventions for
hidradenitis suppurativa. DATA COLLECTION AND ANALYSIS: Two review authors
independently assessed study eligibility and methodological quality and performed
data extraction. Our primary outcomes were quality of life, measured by a
validated dermatology-specific scale, and adverse effects of the interventions.
MAIN RESULTS: Twelve trials, with 615 participants, met our inclusion criteria.
The median number of participants in each trial was 27, and median trial duration
was 16 weeks. The included studies were conducted over a 32-year time period,
from 1983 to 2015. A single RCT that was underpowered to detect clinically
meaningful differences investigated most interventions.There were four trials of
anti-TNF-alpha (tumour necrosis factor-alpha) therapies, which included
etanercept, infliximab, and adalimumab. Adalimumab 40 mg weekly improved the
Dermatology Life Quality Index (DLQI) score in participants with moderate to
severe HS by 4.0 points relative to placebo (95% confidence interval (CI) -6.5 to
-1.5 points), an effect size approximately equal to the DLQI minimal clinically
important difference. We reduced the evidence quality to 'moderate' because the
effect size was based on the results of only one study. In a meta-analysis of two
studies with 124 participants, standard dose adalimumab 40 mg every other week
was ineffective compared with placebo (moderate quality evidence). In a smaller
study of 38 participants, of whom only 33 provided efficacy data, infliximab 5
mg/kg treatment improved DLQI by 8.4 DLQI points after eight weeks. Etanercept 50
mg twice weekly was well tolerated but ineffective.In a RCT of 200 participants,
no difference was found in surgical complications (week one: risk ratio (RR)
0.78, 95% CI 0.58 to 1.05, moderate quality evidence) or risk of recurrence
(after three months: RR 0.96, 95% CI 0.68 to 1.34, moderate quality evidence) in
those randomised to receive a gentamicin-collagen sponge prior to primary closure
compared with primary closure alone.RCTs of other interventions, including
topical clindamycin 1% solution; oral tetracycline; oral ethinylestradiol 50 mcg
with either cyproterone acetate 50 mg or norgestrel 500 mcg; intense pulsed
light; neodymium-doped yttrium aluminium garnet (Nd:YAG) laser; methylene blue
gel photodynamic therapy; and staphage lysate, were relatively small studies,
preventing firm conclusions due to imprecision. AUTHORS' CONCLUSIONS: Many
knowledge gaps exist in RCT evidence for HS. Moderate quality evidence exists for
adalimumab, which improves DLQI score when 40 mg is given weekly, twice the
standard psoriasis dose. However, the 95% confidence interval includes an effect
size of only 1.5 DLQI points, which may not be clinically relevant, and the
safety profile of weekly dosing has not been fully established. Infliximab also
improves quality of life, based on moderate quality evidence.More RCTs are needed
in most areas of HS care, particularly oral treatments and the type and timing of
surgical procedures. Outcomes should be validated, ideally, including a minimal
clinically important difference for HS.
PMID- 26443005
TI - Comparative analyses of fecal microbiota in Tibetan and Chinese Han living at low
or high altitude by barcoded 454 pyrosequencing.
AB - Knowledge about the impact of altitude and ethnicity on human gut microbiota is
currently limited. In this study, fecal microbiota from 12 Tibetans (T group), 11
Chinese Han living in Tibet (HH group) and 12 Chinese Han living in Shaanxi
province (LH group) were profiled by 454 pyrosequencing. Analysis of UniFrac
principal coordinates showed significant structural changes in fecal microbiota
among the three groups. There were significant differences in the composition of
fecal microbiota among the three groups at phylum and genus levels. At the phylum
level, the fecal samples of HH and T groups had higher relative abundances of
Firmicutes, whereas the LH group had a higher relative abundance of
Bacteroidetes. These changes at the phylum level reflected different dominant
genus compositions. Compared with the LH group, changes of Firmicutes and
Bacteroidetes were mainly due to a significant decrease of Prevotella in the HH
group and were primarily attributable to significant decreases of Bacteroides and
Prevotella as well as a significant increase of Catenibacterium in the T group.
In conclusion, our results suggest that high altitude may contribute to shaping
human gut microbiota. Genetic and dietary factors may also explain the different
microbiota compositions between Tibetan and Chinese Han.
PMID- 26443006
TI - Unconventional pairings of spin-orbit coupled attractive degenerate Fermi gas in
a one-dimensional optical lattice.
AB - Understanding novel pairings in attractive degenerate Fermi gases is crucial for
exploring rich superfluid physics. In this report, we reveal unconventional
pairings induced by spin-orbit coupling (SOC) in a one-dimensional optical
lattice, using a state-of-the-art density-matrix renormalization group method.
When both bands are partially occupied, we find a strong competition between the
interband Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) and intraband Bardeen-Cooper
Schrieffer (BCS) pairings. In particular, for the weak and moderate SOC
strengths, these two pairings can coexist, giving rise to a new phase called the
FFLO-BCS phase, which exhibits a unique three-peak structure in pairing momentum
distribution. For the strong SOC strength, the intraband BCS pairing always
dominates in the whole parameter regime, including the half filling. We figure
out the whole phase diagrams as functions of filling factor, SOC strength, and
Zeeman field. Our results are qualitatively different from recent mean-field
predictions. Finally, we address that our predictions could be observed in a
weaker trapped potential.
PMID- 26443007
TI - Hierarchical Pore Development by Plasma Etching of Zr-Based Metal-Organic
Frameworks.
AB - The typically stable Zr-based metal-organic frameworks (MOFs) UiO-66 and UiO-66
NH2 were treated with tetrafluoromethane (CF4 ) and hexafluoroethane (C2 F6 )
plasmas. Through interactions between fluoride radicals from the perfluoroalkane
plasma and the zirconium-oxygen bonds of the MOF, the resulting materials showed
the development of mesoporosity, creating a hierarchical pore structure. It is
anticipated that this strategy can be used as a post-synthetic technique for
developing hierarchical networks in a variety of MOFs.
PMID- 26443008
TI - Differences of eye movement pattern in natural and man-made scenes and image
categorization with the help of these patterns.
AB - In this paper, we investigated the parameters related to eye movement patterns of
individuals while viewing images that consist of natural and man-made scenes.
These parameters are as follows: number of fixations and saccades, fixation
duration, saccade amplitude and distribution of fixation locations. We explored
the way in which individuals look at images of different semantic categories, and
used this information for automatic image classification. We showed that the eye
movements and the contents of eye fixation locations of observers differ for
images of different semantic categories. These differences were used effectively
in automatic image categorization. Another goal of this study was to find the
answer of this question that "whether the image patches of fixation points have
sufficient information for image categorization?" To achieve this goal, a number
of patches with different sizes from two different image categories was
extracted. These patches, which were selected at the location of eye fixation
points, were used to form a feature vector based on K-means clustering algorithm.
Then, different statistical classifiers were trained for categorization purpose.
The results showed that it is possible to predict the image category by using the
feature vectors derived from the image patches. We found significant differences
in parameters of eye movement pattern between the two image categories (average
across subjects). We could categorize images by using these parameters as
features. The results also showed that it is possible to predict the image
category by using image patches around the subjects' fixation points.
PMID- 26443009
TI - Co-sensitization promoted light harvesting with a new mixed-addenda
polyoxometalate [Cu(C12H8N2)2]2[V2W4O19].4H2O in dye-sensitized solar cells.
AB - A di-vanadium-substituted Lindqvist-type polyoxometalate
[Cu(C12H8N2)2]2[V2W4O19].4H2O (1) was hydrothermally synthesized and
characterized structurally by single crystal X-ray diffraction analysis. X-ray
photoelectron spectroscopy and energy disperse spectroscopy tests further prove
the existence of vanadium. Ultraviolet photoelectron spectroscopy and density
functional theoretical studies indicate that the energy level of 1 matches well
with the conduction band of the TiO2. Furthermore, considering the semiconductor
like nature of 1 and the introduction of transition metal element Cu
synchronously extends the absorption to the visible region, which should also be
beneficial to the photovoltaic device performance. 1-Doped TiO2 composites
(denoted as 1@TiO2) have been successfully fabricated by a simple sol-gel method,
and introduced into the dye-sensitized solar cells (DSSCs) as co-sensitizers in
N719-sensitized photoanodes by mixing 1@TiO2 with P25 nanoparticles with
different weight ratios to enhance the photoelectric conversion efficiency. The
investigations show that the DSSC assembled with 1@TiO2/19P25 photoanode has the
best performance and the overall improvement of the efficiency is 21.6% compared
with pure P25. Furthermore, the electrochemical impedance spectroscopy and open
circuit voltage decay investigations show that the cosensitization of 1 and N719
can promote electron transfer and restrain charge recombinations in the DSSCs,
resulting in a longer electron lifetime.
PMID- 26443010
TI - Identifying causal gateways and mediators in complex spatio-temporal systems.
AB - Identifying regions important for spreading and mediating perturbations is
crucial to assess the susceptibilities of spatio-temporal complex systems such as
the Earth's climate to volcanic eruptions, extreme events or geoengineering. Here
a data-driven approach is introduced based on a dimension reduction, causal
reconstruction, and novel network measures based on causal effect theory that go
beyond standard complex network tools by distinguishing direct from indirect
pathways. Applied to a data set of atmospheric dynamics, the method identifies
several strongly uplifting regions acting as major gateways of perturbations
spreading in the atmosphere. Additionally, the method provides a stricter
statistical approach to pathways of atmospheric teleconnections, yielding
insights into the Pacific-Indian Ocean interaction relevant for monsoonal
dynamics. Also for neuroscience or power grids, the novel causal interaction
perspective provides a complementary approach to simulations or experiments for
understanding the functioning of complex spatio-temporal systems with potential
applications in increasing their resilience to shocks or extreme events.
PMID- 26443011
TI - Small-Molecule Allosteric Modulators of the Protein Kinase PDK1 from Structure
Based Docking.
AB - Finding small molecules that target allosteric sites remains a grand challenge
for ligand discovery. In the protein kinase field, only a handful of highly
selective allosteric modulators have been found. Thus, more general methods are
needed to discover allosteric modulators for additional kinases. Here, we use
virtual screening against an ensemble of both crystal structures and comparative
models to identify ligands for an allosteric peptide-binding site on the protein
kinase PDK1 (the PIF pocket). We optimized these ligands through an analog-by
catalog search that yielded compound 4, which binds to PDK1 with 8 MUM affinity.
We confirmed the docking poses by determining a crystal structure of PDK1 in
complex with 4. Because the PIF pocket appears to be a recurring structural
feature of the kinase fold, known generally as the helix alphaC patch, this
approach may enable the discovery of allosteric modulators for other kinases.
PMID- 26443012
TI - Incorporation of nanostructured hydroxyapatite and poly(N-isopropylacrylamide) in
demineralized bone matrix enhances osteoblast and human mesenchymal stem cell
activity.
AB - Demineralized bone matrix (DBM) is currently used in many clinical applications
for bone augmentation and repair. DBM is normally characterized by the presence
of bone morphogenetic proteins. In this study, the authors have optimized methods
to obtain DBM under good manufacturing practice, resulting in enhanced
bioactivity. The processed DBM can be used alone, together with nanostructured
hydroxyapatite (nanoHA), or dispersed in a physiological carrier or hydrogel. In
this study, osteoblasts (MG-63) and human bone marrow derived mesenchymal stem
cells (hMSCs) were cultured on DBM pastes made in phosphate buffered saline
solution or poly(N-isopropylacrylamide) (PNIPAAM) hydrogels with or without
nanoHA. The authors observed that the presence of PNIPAAM reduced osteoblast
adhesion, while the addition of nanoHA increased osteoblast adhesion,
proliferation, interleukin-6 (IL-6) production, and reduced lactate dehydrogenase
(LDH) production. Increasing concentrations of PNIPAAM in combination with nanoHA
further increased osteoblast proliferation, and decreased IL-6 and LDH
production. Incorporation of PNIPAAM in DBM enhanced hMSCs proliferation and
collagen type-I production. Furthermore, a combination of PNIPAAM and nanoHA
further increased alkaline phosphatase and osteocalcin production in hMSCs,
independently from the concentration of PNIPAAM. This study shows that
combinations of DBM with nanoHA and PNIPAAM seem to offer a promising route to
enhance cell activity and induce osteogenic differentiation.
PMID- 26443013
TI - Short-Term Buffers, but Long-Term Suffers? Differential Effects of Negative Self
Perceptions of Aging Following Serious Health Events.
AB - Objectives: Large longitudinal studies show that negative self-perceptions of
aging can be detrimental for health outcomes. However, negative self-perceptions
of aging (i.e., associating aging with physical losses) might be adaptive because
they prepare individuals for serious health events (SHEs), resulting in short
term positive effects as opposed to long-term negative effects on well-being and
health. Method: Longitudinal data from 309 older adults (aged 65 and older) were
analyzed. Short-term (6 months) and long-term (2.5 years) effects after a SHE of
negative self-perceptions of aging on functional limitations (FLs) and negative
affect (NA) were investigated. Results: Results show that in the case of a SHE,
individuals with more negative self-perceptions of aging reported less NA after 6
months but more FLs after 2.5 years. In contrast, individuals with less negative
self-perceptions of aging reported more NA in the short-run but less FLs later
on. Discussion: People with more negative self-perceptions of aging may be
mentally prepared for health events or may have habituated to health declines.
Individuals with more positive self-perceptions, in contrast, may invest a lot in
coping efforts immediately after the health event. Similarities to research on
unrealistic optimism are discussed.
PMID- 26443014
TI - The Relation of Ego Integrity and Despair to Personality Traits and Mental
Health.
AB - Objectives: Existing studies in the Eriksonian tradition found that ego integrity
and despair are important indicators of life-span development. The present study
relates ego integrity and despair to contemporary theories of personality and
mental health. Method: A cross-sectional study of Dutch adults aged between 50
and 95 years (N = 218) was carried out, using the Northwestern Ego Integrity
Scale, the subscales for neuroticism, extraversion, and openness to experience of
the NEO-FFI, the Mental Health Continuum-Short Form, and the Center for
Epidemiological Studies Depression Scale-Short Form. Results: Extraversion and
openness to experience have an indirect relation to ego integrity that is
mediated by well-being. Neuroticism was related to despair and explained the
relationship of depressive symptoms to despair. Chronological age did not
moderate these findings. Discussion: Ego integrity appears to be related to
fluctuating states of mental health, whereas despair is more an expression of a
general trait-like disposition of neuroticism. Implications for further research
are discussed.
PMID- 26443015
TI - Role of Perceived Maternal Favoritism and Disfavoritism in Adult Children's
Psychological Well-Being.
AB - Objectives: The detrimental consequences of parents' differential treatment on
children's well-being have been documented in earlier stages of the life course;
however, little is known about this pattern in midlife. Drawing from theories of
equity and social comparison, we tested whether psychological well-being was
affected only by adult children's perceptions that their mothers treated some
offspring in the family differently or by their perceptions that they were
favored or disfavored. Further, we explored the extent to which these patterns
differed by race. Method: Multilevel regression modeling was conducted using data
collected from 725 adult children nested within 309 later-life families as part
of the Within-Family Differences Study-II. Results: Depressive symptoms were
higher when offspring perceived that they had the most emotional closeness to
mothers or the greatest conflict with mothers. Depressive symptoms were also
higher when respondents identified themselves as being the children in whom the
mothers were most disappointed. Discussion: The findings shed new light on the
role of intergenerational relations in adult children's well-being in midlife by
taking into consideration the respondents' direct reports of their perceptions of
their mothers' favoritism and disfavoritism. Further, the findings provide
evidence that the association between maternal differentiation and psychological
well-being in adulthood is stronger in Black than in White families. These
patterns suggest that the association between psychological well-being and both
favoritism and disfavoritism can be accounted for by processes involving social
comparison rather than equity for both Black and White adult children in midlife.
PMID- 26443017
TI - Atraumatic splenic rupture cases presenting with hemorrhagic shock and
coagulopathy treated by splenic artery occlusion using a microballoon catheter
before splenectomy.
AB - Atraumatic splenic rupture (ASR) is an uncommon pathologic condition in which
bleeding from the spleen occurs for a variety of nontraumatic reasons. While the
current trend in traumatic splenic rupture is nonoperative management including
transcatheter arterial embolization, the current recommendation for the treatment
of most patients with ASR is splenectomy. In this report, we describe two cases
of ASR presenting with hemorrhagic shock and complicated by anticoagulation
therapy. In patients with severe hemorrhagic shock and coagulopathy, a damage
control strategy is recommended. Our successful treatment of these patients
included a three-step strategy as a damage control: (i) rapid transient
hemostasis by splenic artery occlusion using a microballoon catheter, (ii) damage
control resuscitation and (iii) splenectomy as a definitive hemostatic treatment.
PMID- 26443016
TI - Nicotine Exposure During Pregnancy Results in Persistent Midline Epithelial Seam
With Improper Palatal Fusion.
AB - INTRODUCTION: Nonsyndromic cleft palate is a common birth defect (1:700) with a
complex etiology involving both genetic and environmental risk factors. Nicotine,
a major teratogen present in tobacco products, was shown to cause alterations and
delays in the developing fetus. METHODS: To demonstrate the postpartum effects of
nicotine on palatal development, we delivered three different doses of nicotine
(1.5, 3.0, and 4.5mg/kg/d) and sterile saline (control) into pregnant BALB/c mice
throughout their entire pregnancy using subcutaneous micro-osmotic pump. Dams
were allowed to deliver (~day 21 of pregnancy) and neonatal assessments (weight,
length, nicotine levels) were conducted, and palatal tissues were harvested for
morphological and molecular analyses, as well as transcriptional profiling using
microarrays. RESULTS: Consistent administration of nicotine caused developmental
retardation, still birth, low birth weight, and significant palatal size and
shape abnormality and persistent midline epithelial seam in the pups. Through
microarray analysis, we detected that 6232 genes were up-regulated and 6310 genes
were down-regulated in nicotine-treated groups compared to the control. Moreover,
46% of the cleft palate-causing genes were found to be affected by nicotine
exposure. Alterations of a subset of differentially expressed genes were
illustrated with hierarchal clustering and a series of formal pathway analyses
were performed using the bioinformatics tools. CONCLUSIONS: We concluded that
nicotine exposure during pregnancy interferes with normal growth and development
of the fetus, as well results in persistent midline epithelial seam with type B
and C patterns of palatal fusion. IMPLICATIONS: Although there are several
studies analyzing the genetic and environmental causes of palatal deformities,
this study primarily shows the morphological and large-scale genomic outcomes of
gestational nicotine exposure in neonatal mice palate.The previous version was
incorrect. New authors Ali Nawshad, Hasan Otu, Janki Sharma, and Elizabeth
Sheldon have been included in this version; the funding and acknowledgement
sections have been updated accordingly; the article title, some text, and one
supplementary data file have been edited; and the corresponding author has been
changed. The original corresponding author regrets these earlier errors.
PMID- 26443018
TI - Cough Augmentation in Subjects With Duchenne Muscular Dystrophy: Comparison of
Air Stacking via a Resuscitator Bag Versus Mechanical Ventilation.
AB - BACKGROUND: Air stacking improves cough effectiveness in people with Duchenne
muscular dystrophy (DMD) and respiratory muscle weakness. However, it is not
known whether air stacking is more effective via a resuscitator bag or a home
ventilator. METHODS: This prospective randomized study investigated the effect of
air stacking via a volume-cycled home ventilator versus via a resuscitator bag in
participants with DMD. Maximum insufflation capacity and peak expiratory flow
during spontaneous (cough peak flow) and air stacking-assisted cough maneuvers
(air stacking-assisted cough peak flow) were measured. RESULTS: Fifty-two adult
DMD subjects receiving noninvasive ventilation were included in the study: 27
participants performed air stacking via their home ventilator (home-ventilator
group; age = 25.3 +/- 5.1 y; forced vital capacity (FVC) = 809 +/- 555 mL), and
25 participants used a resuscitator bag (resuscitator-bag group; age = 24.7 +/-
5.7 y, FVC = 807 +/- 495 mL). Following a single training session, air stacking
could be performed successfully by 89% (home ventilator) and 88% (resuscitator
bag) of participants. There were comparable maximum insufflation capacities
(1,481 mL for the home-ventilator group vs 1,344 mL for the resuscitator-bag
group, P = .33) and mean air stacking-assisted cough peak flow values (199 L/min
for the home-ventilator group vs 186 L/min for the resuscitator-bag group, P =
.33) between techniques. Air stacking-assisted cough peak flow increased
significantly compared with baseline in both groups (mean increase: +51% [home
ventilator] vs +49% [resuscitator bag], P < .001), with individual air stacking
assisted cough peak flow improvements ranging from -20 to 245%. CONCLUSIONS:
Cough augmentation is an important component of the respiratory management of
people with a neuromuscular disorder. No difference in cough effectiveness as
measured by air stacking-assisted cough peak flow was found in air stacking via a
ventilator compared with via a resuscitator bag. Both methods achieved mean air
stacking-assisted cough peak flow values of >160 L/min. Provision of an
inexpensive resuscitator bag can effectively improve cough capacity, and it is
simple to use, which may improve access to respiratory care in people with DMD.
PMID- 26443019
TI - Zinc Supplementation for One Year Among Children with Cystic Fibrosis Does Not
Decrease Pulmonary Infection.
AB - BACKGROUND: Children with cystic fibrosis may have a deficiency of
micronutrients, including zinc, which may affect their susceptibility to
infections. There is a paucity of data on zinc supplementation among children
with cystic fibrosis. We hypothesized that a pharmacologic dose of zinc
administered daily for 12 months would reduce the need for antibiotics by 50%.
METHODS: This double-blind randomized placebo-controlled trial was conducted
among children with cystic fibrosis to assess the effect of zinc supplementation
on the need for antibiotics and pulmonary function tests. The children, age 5-15
y, of either sex, received either 30-mg zinc tablets or similar looking placebo
tablets daily in addition to standard care. They were followed up every month for
a period of 12 months and whenever they had pulmonary exacerbations. Their serum
zinc was estimated at baseline and at 12 months of enrollment. During each visit,
the children underwent a pulmonary function test and sputum culture. RESULTS: Of
a total of 43 children screened, 40 were enrolled, and of them, 37 completed the
study. The median (interquartile range) number of days of the administration of
antibiotics over 12 months of follow-up among the children receiving zinc was 42
(14-97) d. In the placebo group, it was 38 (15-70) d (P = .79). There were no
significant differences in the percent-of-predicted FEV1 or change in FEV1 values
at 12 months (P = .44). The number of children in whose respiratory specimens
Pseudomonas was isolated was similar for the 2 groups at different time
intervals. The adverse events reported were similar in the 2 groups. CONCLUSION:
We did not find any significant difference in the need for antibiotics, pulmonary
function tests, hospitalization, colonization with Pseudomonas, or the need for
antibiotics for children with cystic fibrosis receiving zinc supplementation of
30 mg/d.
PMID- 26443020
TI - The Risk and Related Factors for Readmission to an ICU Within 7 Days in
Mechanically Ventilated Subjects--A Nationwide Population-Based Cohort Study.
AB - BACKGROUND: Readmission of mechanically ventilated patients to an ICU within 7 d
reflects not only patient safety but also the quality of care of the ICU. This
study aimed to investigate the risk and related factors for readmission to an ICU
within 7 d in mechanically ventilated subjects. METHODS: A total of 658,452
mechanically ventilated subjects discharged from an ICU whose age was >= 17 y old
were obtained from the Taiwan National Health Insurance Research Database for the
period from January 1, 2005, to December 31, 2011. The study applied a
generalized estimating equation logistic regression model to explore whether the
mechanically ventilated subjects were readmitted within 7 d or not and the
related factors. RESULTS: A total of 29,657 subjects were readmitted to the ICU
within 7 d; the total readmission rate was 4.5%. Also, 64.8% of the subjects with
the same diagnosis were returned to the ICU within 7 d. Generalized estimating
equation logistic regression model results showed that the factors related to
higher risk of readmission were male sex, old age, higher comorbidity score,
complications (eg, pneumothorax, subcutaneous emphysema, pneumonia, oxygen
toxicity, pulmonary embolism, or pulmonary edema), use of a private hospital ICU,
ICU stay >=21 d, transfer to a respiratory care center and respiratory care ward,
and subsequent transfer to the regional hospital or district hospital.
CONCLUSIONS: The risk and related factors of a mechanically ventilated subject
whose age is >= 17 y old being readmitted to the ICU within 7 d include subject
characteristics, health status, hospital attributes, and the length of ICU stay.
Therefore, higher risk subjects should receive attention and assessment before
transfer or discharge from the ICU to prevent readmission.
PMID- 26443021
TI - Development of potent in vivo mutagenesis plasmids with broad mutational spectra.
AB - Methods to enhance random mutagenesis in cells offer advantages over in vitro
mutagenesis, but current in vivo methods suffer from a lack of control, genomic
instability, low efficiency and narrow mutational spectra. Using a mechanism
driven approach, we created a potent, inducible, broad-spectrum and vector-based
mutagenesis system in E. coli that enhances mutation 322,000-fold over basal
levels, surpassing the mutational efficiency and spectra of widely used in vivo
and in vitro methods. We demonstrate that this system can be used to evolve
antibiotic resistance in wild-type E. coli in <24 h, outperforming chemical
mutagens, ultraviolet light and the mutator strain XL1-Red under similar
conditions. This system also enables the continuous evolution of T7 RNA
polymerase variants capable of initiating transcription using the T3 promoter in
<10 h. Our findings enable broad-spectrum mutagenesis of chromosomes, episomes
and viruses in vivo, and are applicable to both bacterial and bacteriophage
mediated laboratory evolution platforms.
PMID- 26443022
TI - Filimonas endophytica sp. nov., isolated from surface-sterilized root of Cosmos
bipinnatus.
AB - A Gram-stain-negative, yellow, motile by gliding, filamentous bacterium,
designated SR 2-06T, was isolated from surface-sterilized root of garden cosmos.
16S rRNA gene sequence analysis indicated that SR 2-06T was related most closely
to Filimonas lacunae YT21T of the family Chitinophagaceae at a sequence
similarity of 96.90 %, while levels of similarity to other related taxa were less
than 93.08 %. Strain SR 2-06T exhibited similar features to F. lacunae in that it
contained MK-7 as the major respiratory quinone, and iso-C15 : 1 G, iso-C15 : 0
and a summed feature consisting of C16 : 1omega6c and/or C16 : 1omega7c as the
major fatty acids. However, strain SR 2-06T was distinguished from F. lacunae
using a combination of physiological and biochemical properties. The cellular
polar lipids were phosphatidylethanolamine, unknown aminophospholipids, unknown
aminolipids, an unknown phospholipid and unidentified polar lipids. The DNA G+C
content was 46.0 mol%. The phenotypic and phylogenetic evidence clearly indicates
that strain SR 2-06T represents a novel species of the genus Filimonas, for which
the name Filimonas endophytica sp. nov. is proposed. The type strain is SR 2-06T
( = KCTC 42060T = JCM 19844T).
PMID- 26443024
TI - Rheumatoid arthritis and coronary atherosclerosis: two cousins engaging in a
dangerous liaison.
PMID- 26443023
TI - Efficacy and safety of ticagrelor for long-term secondary prevention of
atherothrombotic events in relation to renal function: insights from the PEGASUS
TIMI 54 trial.
AB - AIMS: We evaluated the relationship of renal function and ischaemic and bleeding
risk as well as the efficacy and safety of ticagrelor in stable patients with
prior myocardial infarction (MI). METHODS AND RESULTS: Patients with a history of
MI 1-3 years prior from PEGASUS-TIMI 54 were stratified based on estimated
glomerular filtration rate (eGFR), with <60 mL/min/1.73 m(2) pre-specified for
analysis of the effect of ticagrelor on the primary efficacy composite of
cardiovascular death, MI, or stroke (major adverse cardiovascular events, MACE)
and the primary safety endpoint of TIMI major bleeding. Of 20 898 patients, those
with eGFR <60 (N = 4849, 23.2%) had a greater risk of MACE at 3 years relative to
those without, which remained significant after multivariable adjustment (hazard
ratio, HRadj 1.54, 95% confidence interval, CI 1.27-1.85, P < 0.001). The
relative risk reduction in MACE with ticagrelor was similar in those with eGFR
<60 (ticagrelor pooled vs. placebo: HR 0.81; 95% CI 0.68-0.96) vs. >=60 (HR 0.88;
95% CI 0.77-1.00, Pinteraction = 0.44). However, due to the greater absolute risk
in the former group, the absolute risk reduction with ticagrelor was higher: 2.7
vs. 0.63%. Bleeding tended to occur more frequently in patients with renal
dysfunction. The absolute increase in TIMI major bleeding with ticagrelor was
similar in those with and without eGFR <60 (1.19 vs. 1.43%), whereas the excess
of minor bleeding tended to be more pronounced (1.93 vs. 0.69%). CONCLUSION: In
patients with a history of MI, patients with renal dysfunction are at increased
risk of MACE and consequently experience a particularly robust absolute risk
reduction with long-term treatment with ticagrelor.
PMID- 26443025
TI - Hijacking the Hedgehog Pathway in Cancer Therapy.
AB - The hedgehog (Hh) signaling pathway, which is almost completely silenced in
normal adult tissues but highly activated in cancer, offers ideal drug targets
for small molecule development. During the last few years, several studies have
indicated that the Hh pathway plays a role in tumor development and maintenance,
and novel drugs inhibiting Hh signaling have been discovered. Although results
from clinical trials in patients harboring activating mutations of Hh have been
promising, there are many controversies regarding the role of the pathway in
tumors that demonstrate ligand over-expression without identified mutations. In
this review, we focus on the function and expression of the Hh pathway in
different tumors and discuss the targeting approaches tested in preclinical and
clinical studies.
PMID- 26443026
TI - Anticancer Activity of Organogallium(III) Complexes in Colon Cancer Cells.
AB - In vitro antitumor activity of various organogallium(III) complexes (1-8) has
been tested against CT26CL25, HCT116, SW480 colon cancer cell lines. CV and MTT
assays were used to assess on the antiproliferative effect of investigated
organogallium(III) complexes. From the investigated complexes, the most active
was found to be tetranuclear compound 8 against CT26CL25 cells. Flow cytometric
analysis of the CT26CL25 cells upon the treatment with 8 was performed in order
to determine the role of apoptosis, caspase activation, autophagy and
proliferation rate on the cell death caused with this compound. Results indicate
cytotoxic potential of the tetranuclear complex 8 by inducing caspase independent
apoptosis and blocking most of the cells before first division.
PMID- 26443027
TI - Design and Synthesis of Novel Schiff Base-Benzothiazole Hybrids as Potential
Epidermal Growth Factor Receptor (EGFR) Inhibitors.
AB - A series of novel Schiff bases -benzothiazole hybrids was designed, synthesized
and evaluated for their anticancer activity by MTT assay and western blot method.
Antiproliferative screening indicated that compound containing dihydroxy
substituents had potent inhibitory activity with IC50 value 34ug/ml against
SKOV3, A2780-S and A2780-CR cell lines. It showed more potent cytotoxicity in
combination with cisplatin and paclitaxel than alone in the selected cell lines
(SKOV3, A2780 and A2780-CR models). The in vitro cytotoxicity of the compounds on
IOSE 364 cell line was evaluated to establish the selectivity. Molecular docking
study exhibited good binding against epidermal growth factor receptor, which was
further ascertained by immunoblot assay using specific antibody against
phosphorylated EGFR, and thus unravelling the targeted anticancer mechanism.
PMID- 26443028
TI - Creating a Common Curriculum for the DSM-5: Lessons in Collaboration.
PMID- 26443029
TI - Integrated Care Training in Canada: Challenges and Future Directions.
PMID- 26443030
TI - The University of Manitoba Psychiatry Toolkit: Development and Evaluation.
AB - OBJECTIVE: The authors developed and measured the subsequent utilization of a web
based point-of-care information tool and meta-search filter, the University of
Manitoba Psychiatry Toolkit, as well as conduct an evaluation of its impact on
physicians' information seeking. METHODS: Evaluation entailed analysis of toolkit
web page utilization data from user visits to the web-based toolkit, as well as
an online survey distributed to psychiatrists and resident trainees to assess
information gathering behaviors and attitudes regarding various sources of
medical information. RESULTS: Electronic resources and colleagues were the
preferred sources for gathering health information, while inadequate time and
search skills were ranked as important barriers. Age and physician cadre
influenced toolkit use. Majority of respondents used the Psychiatry Toolkit to
answer a clinical question, and urgency of the clinical problem influenced their
decision to use it. CONCLUSIONS: The Psychiatry Toolkit assists psychiatrists and
residents in finding answers to clinical questions arising at point-of-care,
helping enhance the ongoing educational needs of physicians.
PMID- 26443031
TI - Myocardial and Peripheral Ischemia Causes an Increase in Circulating Pregnancy
Associated Plasma Protein-A in Non-atherosclerotic, Non-heparinized Pigs.
AB - The usefulness of circulating pregnancy-associated plasma protein-A (PAPP-A) as a
biomarker for acute coronary syndrome (ACS) is widely debated. We used the pig as
a model to assess PAPP-A dynamics in the setting of myocardial ischemia.
Induction of myocardial ischemia by ligation of the left anterior descending
(LAD) coronary artery caused a systemic rise in PAPP-A. However, the ischemic
myocardium was excluded as the source of PAPP-A. Interestingly, induction of
ischemia in peripheral tissues by ligation of the left femoral artery caused a
systemic rise in PAPP-A originating from the left hind limb. This is the first
study to demonstrate PAPP-A elevations in the absence of atherosclerosis or
heparin during myocardial ischemia. Our findings thus add to the current
discussion of the usefulness of PAPP-A as a biomarker for ACS.
PMID- 26443032
TI - Fungal phytotoxins with potential herbicidal activity: chemical and biological
characterization.
AB - Covering: 2007 to 2015 Fungal phytotoxins are secondary metabolites playing an
important role in the induction of disease symptoms interfering with host plant
physiological processes. Although fungal pathogens represent a heavy constraint
for agrarian production and for forest and environmental heritage, they can also
represent an ecofriendly alternative to manage weeds. Indeed, the phytotoxins
produced by weed pathogenic fungi are an efficient tool to design natural, safe
bioherbicides. Their use could avoid that of synthetic pesticides causing
resistance in the host plants and the long term impact of residues in
agricultural products with a risk to human and animal health. The isolation and
structural and biological characterization of phytotoxins produced by pathogenic
fungi for weeds, including parasitic plants, are described. Structure activity
relationships and mode of action studies for some phytotoxins are also reported
to elucidate the herbicide potential of these promising fungal metabolites.
PMID- 26443034
TI - Delusional Infestation With Black Mold Presenting to the General Hospital.
PMID- 26443033
TI - An improved chloride-conducting channelrhodopsin for light-induced inhibition of
neuronal activity in vivo.
AB - Channelrhodopsins are light-gated cation channels that have been widely used for
optogenetic stimulation of electrically excitable cells. Replacement of a
glutamic acid in the central gate with a positively charged amino acid residue
reverses the ion selectivity and produces chloride-conducting ChRs (ChloCs).
Expressed in neurons, published ChloCs produced a strong shunting effect but also
a small, yet significant depolarization from the resting potential. Depending on
the state of the neuron, the net result of illumination might therefore be
inhibitory or excitatory with respect to action potential generation. Here we
report two additional amino acid substitutions that significantly shift the
reversal potential of improved ChloC (iChloC) to the reversal potential of
endogenous GABAA receptors. As a result, light-evoked membrane depolarization was
strongly reduced and spike initiation after current injection or synaptic
stimulation was reliably inhibited in iChloC-transfected neurons in vitro. In the
primary visual cortex of anesthetized mice, activation of iChloC suppressed
spiking activity evoked by visual stimulation. Due to its high operational light
sensitivity, iChloC makes it possible to inhibit neurons in a large volume of
brain tissue from a small, point-like light source.
PMID- 26443035
TI - Building Bridges Between Silos: An Outcomes-Logic Model for a Multidisciplinary,
Subspecialty Fellowship Education Program.
PMID- 26443038
TI - Study of electronic and magnetic properties and related x-ray absorption
spectroscopy of ultrathin Co films on BaTiO3.
AB - We present a first-principles study of electronic and magnetic properties of thin
Co films on a BaTiO3(0 0 1) single crystal. The crystalline structure of 1-3
monolayer thick Co films was determined and served as input for calculations of
the electronic and magnetic properties of the films. The estimation of exchange
constants indicates that the Co films are ferromagnetic with a high critical
temperature, which depends on the film thickness and the interface geometry. In
addition, we calculated x-ray absorption spectra, related magnetic circular
dichroism (XMCD) and linear dichroism (XLD) of the Co L 2, 3 edges as a function
of Co film thickness and ferroelectric polarization of BaTiO3. We found
characteristic features, which depend strongly on the magnetic properties and the
structure of the film. While there is only a weak dependence of XMCD spectra on
the ferroelectric polarization, the XLD of the films is much more sensitive to
the polarization switching, which could possibly be observed experimentally.
PMID- 26443037
TI - Association of impaired left ventricular twisting-untwisting with vascular
dysfunction, neurohumoral activation and impaired exercise capacity in
hypertensive heart disease.
AB - AIMS: We investigated the association between left ventricular (LV) torsional
deformation and vascular dysfunction, fibrosis, neurohumoral activation, and
exercise capacity in patients with normal ejection fraction METHODS AND RESULTS:
In 320 newly-diagnosed untreated hypertensive patients and 160 controls, we
measured: pulse wave velocity (PWV); coronary flow reserve (CFR) by Doppler
echocardiography; global longitudinal strain and strain rate, peak twisting, the
percentage changes between peak twisting, and untwisting at mitral valve opening
(%dpTw - UtwMVO ), at peak (%dpTw - UtwPEF ), and the end of early LV diastolic
filling (%dpTw - UtwEDF ) by speckle tracking imaging; transforming growth factor
(TGFb-1), metalloproteinase-9 (MMP-9), tissue inhibitor of matrix
metalloptoteinase-1(TIMP-1), markers of collagen synthesis, and N-terminal pro
brain natriuretic peptide (NT-proBNP). Oxygen consumption (VO2 ), measured by
means of cardiopulmonary exercise test, was assessed in a subset of 80 patients.
The PWV, CFR, longitudinal strain and strain rate, %dpTw-UtwMVO , %dpTw-UtwPEF ,
and %dpTw-UtwEDF were impaired in hypertensive patients compared with controls.
In multivariable analysis, CFR, PWV, LV mass, and systolic blood pressure were
independent determinants of longitudinal strain, strain rate, and untwisting
markers (P < 0.05). Increased TGFb-1 was related with increased collagen
synthesis markers, TIMP-1 and MMP-9 and these biomarkers were associated with
impaired longitudinal systolic strain rate, untwisting markers, CFR and PWV (P <
0.05). Delayed untwisting as assessed by reduced %dpTw - UtwEDF was related with
increased NT-proBNP and reduced VO2 (P < 0.05). CONCLUSIONS: Impaired LV
untwisting is associated with increased arterial stiffness and coronary
microcirculatory dysfunction, and is linked to reduced exercise capacity and
neurohumoral activation in hypertensive heart disease. A fibrotic process may be
the common link between vascular dysfunction and abnormal myocardial deformation.
PMID- 26443036
TI - Health Care Utilization by Body Mass Index in a Pediatric Population.
AB - OBJECTIVE: We tested the hypothesis that the frequency of emergency department
(ED) visits, outpatient clinic visits, and hospitalizations were higher among
children with higher body mass index (BMI) categories, even after controlling for
demographics, socioeconomic status, and presence of other chronic medical
conditions. METHODS: We obtained electronic height, weight, and utilization data
for all residents of Olmsted County, Minnesota, aged 2 to 18 years on January 1,
2005 (n = 34,335), and calculated baseline BMI (kg/m(2)). At least 1 BMI
measurement and permission to use medical record information was available for
19,771 children (58%); 19,528 with follow-up comprised the final cohort. BMIs
were categorized into underweight/healthy weight (<85th percentile), overweight
(85th to <95th percentile), and obese (>=95th percentile). Negative binomial
models were used to compare the rate of utilization across BMI categories.
Multivariable models were used to adjust for the effects of age, race, sex,
socioeconomic status, and chronic medical conditions. RESULTS: Compared to
children with BMI <85th percentile, overweight and obese status were associated
with increased ED visits (adjusted incident rate ratio [IRR] 1.16, 95% confidence
interval [CI] 1.10, 1.23; and IRR 1.27, 95% CI 1.19, 1.35, respectively; P for
trend <.0001), and outpatient clinic visits (IRR 1.05, 95% CI 1.02, 1.08; and IRR
1.07, 95% CI 1.04, 1.11, respectively; P for trend <.0001). No associations were
observed between baseline BMI category and hospitalizations in the adjusted
analyses. CONCLUSIONS: Children who are overweight or obese utilize the ED and
outpatient clinics more frequently than those who are underweight/healthy weight,
but are not hospitalized more frequently.
PMID- 26443039
TI - Evidence of impaired carbohydrate assimilation in euthyroid patients with
Hashimoto's thyroiditis.
AB - BACKGROUND/OBJECTIVES: Hashimoto's thyroiditis (HT) represents a wide-spread
autoimmune disease. In euthyroid patients with HT, an impaired assimilation of
common carbohydrates has been observed. Our objectives were to compare the
frequency of (1) fructose (FM), lactose (LM) and sorbitol malassimilation (SM),
(2) gastrointestinal symptoms (GS) following carbohydrate ingestion and (3)
recurrent GS relevant to the participants' daily lives. SUBJECTS/METHODS: We
conducted a prospective case-control study of 45 ambulatory patients with HT and
38 healthy volunteers, matched with regard to age, gender and area of origin.
Hydrogen breath tests with fructose, lactose, sorbitol and glucose were
performed, the lactose testing additionally comprising measurements of capillary
blood glucose (cBG). GS during the tests and recurrent GS concerning the
participants' daily lives were assessed. A food-frequency questionnaire was
administered. RESULTS: FM was diagnosed in 48.9% of patients compared with 26.3%
of the control group (P=0.035). In all, 42.2% of patients with HT and 21.1% of
healthy controls showed LM (P=0.04). FM and/or LM was present in 73.3% of the
patients and in 42.1% of healthy controls (P=0.004). GS after the ingestion of
fructose (P=0.003) or lactose (P=0.025) and recurrent GS were significantly more
prevalent in the case group. The consumption of free fructose, lactose or
sorbitol did not differ. CONCLUSIONS: Carbohydrate malassimilation and
gastrointestinal complaints are frequent in euthyroid patients with HT, leading
to novel clinical and pathophysiological considerations and concepts.
PMID- 26443040
TI - Adolescents' beverage choice at school and the impact on sugar intake.
AB - BACKGROUND/OBJECTIVES: To examine students' beverage choice in school, with
reference to its contribution to students' intake of non-milk extrinsic (NME)
sugars. SUBJECTS/METHODS: Beverage and food selection data for students aged 11
18 years (n=2461) were collected from two large secondary schools in England, for
a continuous period of 145 (school A) and 125 (school B) school days. Descriptive
analysis followed by cluster analysis of the beverage data were performed
separately for each school. RESULTS: More than a third of all items selected by
students were beverages, and juice-based beverages were students' most popular
choice (school A, 38.6%; school B, 35.2%). Mean NME sugars derived from beverages
alone was high (school A, 16.7 g/student-day; school B, 12.9 g/student-day).
Based on beverage purchases, six clusters of students were identified at each
school (school A: 'juice-based', 'assorted', 'water', 'cartoned flavoured milk',
'bottled flavoured milk', 'high volume juice-based'; school B: 'assorted', 'water
with juice-based', 'sparkling juice/juice-based', 'water', 'high volume water',
'high volume juice-based'). Both schools included 'high volume juice-based'
clusters with the highest NME sugar means from beverages (school A, 28.6
g/student-day; school B, 24.4 g/student-day), and 'water' clusters with the
lowest. A hierarchy in NME sugars was found according to cluster; students in the
'high volume juice-based' cluster returned significantly higher levels of NME
sugars than students in other clusters. CONCLUSIONS: This study reveals the
contribution that school beverages combined with students' beverage choice
behaviour is making to students' NME sugar intake. These findings inform school
food initiatives, and more generally public health policy around adolescents'
dietary intake.
PMID- 26443041
TI - Transmission of energy-saving efficiency from obese parents to their offspring:
the Korean National Health and Nutrition Examination Survey 2007-2011.
AB - BACKGROUND/OBJECTIVES: Concerns of a growing obesity epidemic have increased
since the association between obesity in parents and that in offspring was
reported. However, the evidence regarding whether the energy-saving efficiency of
obese parents is conveyed to their offspring and the duration of the expression
of such transmitted efficiency is limited. SUBJECTS/METHODS: We included 7647
matching sets of parent-offspring trios from South Korea. Multiple linear
regression models were performed to estimate the energy-saving efficiency, as
assessed by the associations between energy intake and obesity-related indices
(waist-to-height ratio, waist circumference and body mass index z-score), and to
compare the energy-saving efficiency of offspring of obese and non-obese parents.
All analyses were based on a complex sample design and were stratified by gender
and age. RESULTS: We identified a parental influence on obesity, that is, the
more obese the parent, the higher the obesity-related indices of their offspring,
in both genders and all age groups. The energy-saving efficiency of child
offspring was highest when both parents were obese and lowest when both were non
obese; this difference was significant (P<0.05) with regard to the energy-saving
efficiency of all types of intake studied, except fat. However, the energy-saving
efficiency of obese and non-obese parents did not differ when their offspring
were adolescents and adults. CONCLUSIONS: The critical window for transmission of
energy-saving efficiency is limited to childhood. These findings suggest that
children of obese parents should be more emphatically advised to maintain a
balanced diet and to engage in regular physical activity.
PMID- 26443042
TI - Association between bariatric surgery and quality of life.
PMID- 26443043
TI - Update on food allergy.
AB - Food allergies are a global health issue with increasing prevalence. Allergic
reactions can range from mild local symptoms to severe anaphylactic reactions.
Significant progress has been made in diagnostic tools such as component-resolved
diagnostics and its impact on risk stratification as well as in therapeutic
approaches including biologicals. However, a cure for food allergy has not yet
been achieved and patients and their families are forced to alter eating habits
and social engagements, impacting their quality of life. New technologies and
improved in vitro and in vivo models will advance our knowledge of the
pathogenesis of food allergies and multicenter-multinational cohort studies will
elucidate interactions between genetic background, lifestyle, and environmental
factors. This review focuses on new insights and developments in the field of
food allergy and summarizes recently published articles.
PMID- 26443044
TI - Using Improvement Methodology to Optimize Echocardiographic Imaging of Coronary
Arteries in Children.
AB - BACKGROUND: According to the American Society of Echocardiography, coronary
artery (CA) imaging is recommended in pediatric examinations to identify CA
anomalies. A review of the authors' center's echocardiographic studies revealed
that CA images were often nondiagnostic. The aim of this study was to utilize
quality improvement methodology to increase the percentage of first-time
pediatric studies with definitive CA identification from a baseline of 45% to a
goal of at least 75% in 9 months. METHODS: A scoring system was developed to
characterize the completeness of CA imaging. One point was scored for
demonstration of each of the following: right CA origin by two-dimensional
imaging, right CA origin by color flow Doppler imaging, left CA origin by two
dimensional imaging, and left CA origin by color flow Doppler imaging. A score of
4 was considered to represent definitive imaging. A baseline was obtained on 100
first-time echocardiograms with normal findings. During the intervention, 10
randomly selected first-time studies with normal findings were scored weekly for
assessment of CA imaging. Interventions were focused on the following domains:
excellence in image quality, shared ownership, transparency, and effective
communication. Key interventions included labeling CA images, requiring two
dimensional and color Doppler images, optimization of settings, and elimination
of macros for CA reporting. RESULTS: The percentage of definitive CA
identification increased from 45% to 82.5% over 4 months and was sustained for 7
months. Accurate reporting of incomplete CA imaging increased from 17% to 77.5%.
CONCLUSIONS: Improved pediatric CA imaging and reporting were achieved through
the implementation of key interventions.
PMID- 26443045
TI - The Application of Intravascular Ultrasound to Evaluate Pulmonary Vascular
Properties and Mortality in Patients with Pulmonary Arterial Hypertension.
AB - BACKGROUND: The aim of this study was to explore the application of intravascular
ultrasound (IVUS) to evaluate pulmonary vascular properties and mortality in
patients with pulmonary arterial hypertension (PAH). METHODS: Patients (n = 51)
with systolic pulmonary artery pressures >= 40 mm Hg on echocardiography were
prospectively enrolled. All patients underwent right-heart catheterization and
IVUS and were divided into three groups: PAH associated with connective tissue
diseases (group 1, n = 25), PAH due to other causes (group 2, n = 15), and
patients with connective tissue diseases without pulmonary hypertension (group 3,
n = 11). PAH groups (groups 1 and 2) were divided into distal (n = 22) and
proximal (n = 18) remodeling subtypes on the basis of IVUS results. All patients
were followed (19 +/- 10 months) to compare the differences among clinical
variables, pulmonary vascular properties, and survival rates. RESULTS: A total of
408 segments of pulmonary arteries were studied. The PAH groups demonstrated a
greater mean wall thickness than group 3 (P < .01 for all). Pulmonary vascular
mechanical properties, including compliance, distensibility, elastic modulus, and
stiffness index beta, were found to be worse in the PAH groups than in group 3 (P
< .01 for all), but they tended to be better in group 1 than in group 2. An
inverse exponential association was found between pulmonary vascular mechanical
properties and hemodynamics, with R(2) values ranging from 0.54 to 0.78 (P <
.001). In the PAH groups, the mortality in group 1 was similar to that in group 2
(12% vs 13%, P > .05), while the distal remodeling subtype had higher mortality
than the proximal remodeling subtype (23% vs 0%, P < .05). CONCLUSIONS: IVUS is
useful in PAH assessment by evaluating pulmonary vascular properties and
predicting mortality. The classification of the proximal and distal remodeling
type of PAH may be proposed to predict mortality and evaluate the prognosis of
patients with PAH in clinical practice.
PMID- 26443046
TI - Chronic Inflammatory Disease Is an Independent Risk Factor for Coronary Flow
Velocity Reserve Impairment Unrelated to the Processes of Coronary Artery Calcium
Deposition.
AB - BACKGROUND: Chronic inflammatory disease (CID) is a complex multisystem disease
characterized by chronic inflammation, which can lead to coronary microvascular
dysfunction (CMD) and can also predispose to coronary artery calcium deposition,
even in the absence of obstructive coronary artery disease. METHODS: Twenty-one
patients with systemic lupus erythematosus (SLE; mean age, 60 +/- 11 years), 21
patients with systemic sclerosis (SSc; mean age, 66 +/- 11 years), 32 patients
with rheumatoid arthritis (RA; mean age, 65 +/- 9 years), and 23 control subjects
with comparable traditional risk factors for coronary artery disease (mean age,
65 +/- 10 years) were prospectively enrolled in the outpatient clinic. All study
participants underwent transthoracic Doppler-derived echocardiography for
coronary flow velocity reserve (CFVR) measurement in the left anterior descending
coronary artery; CFVR < 2.5 defined CMD. Coronary artery calcium score in the
left anterior descending coronary artery was also assessed by computed
tomography. RESULTS: None of study participants had obstructive coronary artery
disease. The prevalence of CMD was 26% in the control group, 67% in the SLE
group, 76% in the SSc group, and 63% in the RA group (P < .05, CID groups vs
control group). CFVR was significantly lower in all three CID groups than in the
control group (control group, 3.01 +/- 0.72; SLE group, 2.23 +/- 0.71; SSc group,
2.14 +/- 0.54; RA group, 2.33 +/- 0.62; P < .05, CID groups vs control group). In
contrast, coronary artery calcium scores were similar in the four groups and had
no relation to CMD. The odds ratios for CMD in patients with SLE, SSc, and RA
were 16.70, 25.78, and 8.44 (P < .05) after adjusting for age, body mass index,
the presence or absence of anemia, and hemoglobin level. Multiple linear
regression analysis showed that only the presence of CID was independently
associated with reduced CFVR among all study participants. CONCLUSIONS: CID
strongly contributes to CMD identified by qualitative evaluation of CFVR
independently of traditional coronary risk factors of atherosclerosis but does
not predispose to coronary artery calcification.
PMID- 26443047
TI - Is this STS work-related? ISO 1999 predictions as an adjunct to clinical
judgment.
AB - BACKGROUND: Physicians and audiologists are often asked to decide whether
standard threshold shifts (STSs) are work-related; epidemiological data can
inform these decisions. METHODS: Predictions of ISO (2013) for both age-related
and noise-induced threshold shifts, for the 2, 3, and 4 kHz average used in
calculating OSHA STSs, are presented, in tables, graphs, and an Excel spreadsheet
calculator. Specifically, the ISO 1999 model estimates age-related thresholds
based on age and sex; it estimates noise-induced threshold shifts based on noise
level and duration. It specifies that to estimate the final hearing thresholds
for a person of given percentile, age, sex, and noise exposure, the expected age
related threshold is to be added to the expected noise-induced threshold shift.
Examples show how these data can predict the relative contributions of aging and
occupational noise to an STS. RESULTS: Early-career STSs, especially with high
levels of noise exposure, are more likely to be primarily noise-induced. After
the first decade of exposure, most STSs will be primarily age-related.
CONCLUSION: Given a worker's age, sex, and occupational noise exposure history,
ISO 1999 estimates of the expected contributions of aging and noise can
supplement clinical judgment.
PMID- 26443048
TI - Simvastatin inhibits neural cell apoptosis and promotes locomotor recovery via
activation of Wnt/beta-catenin signaling pathway after spinal cord injury.
AB - Statins exhibit neuroprotective effects after spinal cord injury (SCI). However,
the molecular mechanism underlying these effects remains unknown. This study
demonstrates that the hydroxymethylglutaryl coenzyme A reductase inhibitor
simvastatin (Simv) exhibits neuroprotective effects on neuronal apoptosis and
supports functional recovery in a rat SCI model by activating the Wnt/beta
catenin signaling pathway. In specific, Simv administration after SCI
significantly up-regulated the expression of low density lipoprotein receptor
related protein 6 phosphorylation and beta-catenin protein, increased the mRNA
expression of lymphoid enhancer factor-1 and T-cell factor-1, and suppressed the
expression of beta-catenin phosphorylation in the spinal cord neurons. Simv
enhanced motor neuronal survival in the spinal cord anterior horn and decreased
the lesion of spinal cord tissues after SCI. Simv administration after SCI also
evidently reduced the expression levels of Bax, active caspase-3, and active
caspase-9 in the spinal cord neurons and the proportion of transferase UTP nick
end labeling (TUNEL)-positive neuron cells, but increased the expression level of
Bcl-2 in the spinal cord neurons. However, the anti-apoptotic effects of Simv
were reduced in cultured spinal cord nerve cells when the Wnt/beta-catenin
signaling pathway was suppressed in the lipopolysaccharide-induced model.
Furthermore, the Basso, Beattie, and Bresnahan scores indicated that Simv
treatment significantly improved the locomotor functions of rats after SCI. This
study is the first to report that Simv exerts neuroprotective effects by reducing
neuronal apoptosis, and promoting functional and pathological recovery after SCI
by activating the Wnt/beta-catenin signaling pathway. We verified the
neuroprotective properties associated with simvastatin following spinal cord
injury (SCI). Simvastatin reduced neuronal apoptosis, improved the functional and
pathological recovery via activating Wnt/beta-catenin signal pathway, however,
the anti-apoptosis effects of simvastatin were reversed following suppressing
Wnt/beta-catenin signaling pathway in primary spinal cord neurons. The
significant findings may provide clinical therapeutic value of simvastatin for
treating SCI.
PMID- 26443049
TI - Psychobiology of threat appraisal in the context of psychotic experiences: a
selective review.
AB - A key factor in the transition to psychosis is the appraisal of anomalous
experiences as threatening. Cognitive models of psychosis have identified
attentional and interpretative biases underlying threat-based appraisals. While
much research has been conducted into these biases within the clinical and
cognitive literature, little examination has occurred at the neural level.
However, neurobiological research in social cognition employing threatening
stimuli mirror cognitive accounts of maladaptive appraisal in psychosis. This
review attempted to integrate neuroimaging data regarding social cognition in
psychosis with the concepts of attentional and interpretative threat biases.
Systematic review methodology was used to identify relevant articles from
Medline, PsycINFO and EMBASE, and PubMed databases. The selective review showed
that attentional and interpretative threat biases relate to abnormal activation
of a range of subcortical and prefrontal structures, including the amygdala,
insula, hippocampus, anterior cingulate, and prefrontal cortex, as well as
disrupted connectivity between these regions, when processing threatening and
neutral or ambiguous stimuli. Notably, neural findings regarding the
misattribution of threat to neutral or ambiguous stimuli presented a more
consistent picture. Overall, however, the findings for any specific emotion were
mixed, both in terms of the specific brain areas involved and the direction of
effects (increased/decreased activity), possibly owing to confounds including
small sample sizes, varying experimental paradigms, medication, and
heterogeneous, in some cases poorly characterised, patient groups. Further
neuroimaging research examining these biases by employing experimentally induced
anomalous perceptual experiences and well-characterised large samples is needed
for greater aetiological specificity.
PMID- 26443050
TI - Suicidality in schizophrenia spectrum disorders: the relationship to
hallucinations and persecutory delusions.
AB - BACKGROUND: Assessment of suicide risk is crucial in schizophrenia and results
concerning risk contributed by hallucinations and persecutory delusions are
inconsistent. We aimed to determine factors associated with suicidal ideation and
plans at the time of acute admission in patients suffering from schizophrenia
spectrum disorders. METHODS: One hundred and twenty-four patients older than 18
years admitted to an acute psychiatric ward due to psychosis were consecutively
included. Predictors of suicidal ideation and suicide plans at the time of
admission were examined with multinominal logistic regression and structural
equation modelling (SEM). The study design was pragmatic, thus entailing a
clinically relevant representation. RESULTS: Depression Odds Ratio (OR) 12.9,
Drug use OR 4.07, Hallucinations OR 2.55 and Negative symptoms OR 0.88
significantly predicted Suicidal ideation. Suspiciousness/ Persecution did not.
Only Depression and Hallucinations significantly predicted Suicide plans. In the
SEM-model Anxiety, Depression and Hopelessness connected
Suspiciousness/Persecution, Hallucinations and Lack of insight with Suicidal
ideation and Suicide plans. CONCLUSIONS: The study contributes to an increasing
evidence base supporting an association between hallucinations and suicide risk.
We want to emphasise the importance of treating depression and hallucinations in
psychotic disorders, reducing hopelessness while working with insight and
reducing drug abuse in order to lower suicide risk. TRIAL REGISTRATION:
ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/NCT00932529.
PMID- 26443051
TI - The measurement invariance of schizotypy in Europe.
AB - The short version of the Oxford-Liverpool Inventory of Feelings and Experiences
(sO-LIFE) is a widely used measure assessing schizotypy. There is limited
information, however, on how sO-LIFE scores compare across different countries.
The main goal of the present study is to test the measurement invariance of the
sO-LIFE scores in a large sample of non-clinical adolescents and young adults
from four European countries (UK, Switzerland, Italy, and Spain). The scores were
obtained from validated versions of the sO-LIFE in their respective languages.
The sample comprised 4190 participants (M=20.87 years; SD=3.71 years). The study
of the internal structure, using confirmatory factor analysis, revealed that both
three (i.e., positive schizotypy, cognitive disorganisation, and introvertive
anhedonia) and four-factor (i.e., positive schizotypy, cognitive disorganisation,
introvertive anhedonia, and impulsive nonconformity) models fitted the data
moderately well. Multi-group confirmatory factor analysis showed that the three
factor model had partial strong measurement invariance across countries. Eight
items were non-invariant across samples. Significant statistical differences in
the mean scores of the s-OLIFE were found by country. Reliability scores,
estimated with Ordinal alpha ranged from 0.75 to 0.87. Using the Item Response
Theory framework, the sO-LIFE provides more accuracy information at the medium
and high end of the latent trait. The current results show further evidence in
support of the psychometric proprieties of the sO-LIFE, provide new information
about the cross-cultural equivalence of schizotypy and support the use of this
measure to screen for psychotic-like features and liability to psychosis in
general population samples from different European countries.
PMID- 26443052
TI - Religiosity and mental health of pre-adolescents with psychiatric problems and
their parents: the TRAILS study.
AB - BACKGROUND: This study investigated the association between the religiosity of
parents and pre-adolescents, and pre-adolescents' psychiatric problems. METHOD:
In a clinic-referred cohort of 543 pre-adolescents at least once referred to a
mental health outpatient clinic mental health problems were assessed using self
reports (Youth Self-Report; YSR), parent reports (Child Behavior Checklist;
CBCL), and teacher reports (Teacher's Report Form; TRF) of child behavioral and
emotional problems. Paternal, maternal, and pre-adolescent religiosity were
assessed by self-report. MANCOVAs were performed for internalizing and
externalizing problems as dependent variables, with maternal religiosity,
paternal religiosity, pre-adolescent religiosity, parental religious harmony, and
gender as independent variables, and socioeconomic status and divorce as
covariates. RESULTS: Internalizing problems. Pre-adolescents of actively
religious mothers had more internalizing symptoms than pre-adolescents of
nonreligious mothers. Harmony and gender did not significantly affect the
association between maternal religiosity and internalizing problems.
Externalizing problems. No associations between religiosity of pre-adolescents,
religiosity of mothers, religiosity of fathers and/or harmony of parents and
externalizing problem behavior have been found. DISCUSSION AND CONCLUSIONS:
Overall, associations between mental health and religiosity were modest to
absent. Results are discussed in the context of a clinic-referred cohort, the
quest phase of internalizing religious beliefs and role modeling of parents.
PMID- 26443053
TI - Increased affective reactivity to neutral stimuli and decreased maintenance of
affective responses in bipolar disorder.
AB - BACKGROUND: Affective dysregulation is a core feature of bipolar disorder (BD)
and a significant predictor of clinical and functional outcome. Affective
dysregulation can arise from abnormalities in multiple processes. This study
addresses the knowledge gap regarding the precise nature of the processes that
may be dysregulated in BD and their relationship to the clinical expression of
the disorder. METHODS: Patients with BD (n=45) who were either in remission or in
a depressive or manic state and healthy individuals (n=101) were compared in
terms of the intensity, duration and physiological response (measured using inter
beat intervals and skin conductance) to affective and neutral pictures during
passive viewing and during experiential suppression. RESULTS: Compared to healthy
individuals, patients with BD evidenced increased affective reactivity to neutral
pictures and reduced maintenance of subjective affective responses to all
pictures. This pattern was present irrespective of clinical state but was more
pronounced in symptomatic patients, regardless of polarity. Patients, regardless
of symptomatic status, were comparable to healthy individuals in terms of
physiological arousal and voluntary control of affective responses. CONCLUSION:
Our study demonstrates that increased affective reactivity to neutral stimuli and
decreased maintenance of affective responses are key dimensions of affective
dysregulation in BD.
PMID- 26443054
TI - Effect of DISC1 polymorphisms on the long-term course of neurocognitive deficits
in non-affective psychosis.
AB - Neurocognitive deficits are core symptoms of schizophrenia that determine a
poorer outcome. High variability in the progression of neuropsychological
deficits in schizophrenia has been described. It is still unknown whether genetic
variations can affect the course of cognitive deficits. Variations in the
Disrupted in Schizophrenia 1 (DISC1) gene have previously been associated with
neurocognitive deficits. This study investigated the association between 3 DISC1
polymorphisms (rs6675281 (Leu607Phe), rs1000731, and rs821616 (Ser704Cys)) and
long-term (3 years) cognitive performance. One-hundred-thirty-three Caucasian
drug-naive patients experiencing a first episode of non-affective psychosis were
genotyped. Cognitive function was assessed at baseline and after 3 years of
initiating treatment. Other clinical and socio-demographic variables were
recorded to eliminate potential confounding effects. Patients carrying the A
allele of rs1000731 exhibited a significant improvement in Working Memory and
Attention domains, and the homozygosity of the A allele of rs821616 showed a
significant improvement in Motor Dexterity performance over 3 years of follow-up.
In conclusion, DISC1 gene variations may affect the course of cognitive deficits
found in patients suffering from the first episode of non-affective psychosis.
PMID- 26443055
TI - The Rubber Hand Illusion paradigm as a sensory learning process in patients with
schizophrenia.
AB - OBJECTIVE: The Rubber Hand Illusion (RHI) has previously been used to depict the
hierarchy between visual, tactile and perceptual stimuli. Studies on
schizophrenia inpatients (SZs) have found mixed results in the ability to first
learn the illusion, and have yet to explain the learning process involved. This
study's aim was two-fold: to examine the learning process of the RHI in SZs and
healthy controls over time, and to better understand the relationship between
psychotic symptoms and the RHI. METHOD: Thirty schizophrenia inpatients and 30
healthy controls underwent five different trials of the RHI over a two-week
period. RESULTS: As has been found in previous studies, SZs felt the initial
illusion faster than healthy controls did, but their learning process throughout
the trials was inconsistent. Furthermore, for SZs, no correlations between
psychotic symptoms and the learning of the illusion emerged. CONCLUSION: Healthy
individuals show a delayed reaction to first feeling the illusion (due to latent
inhibition), but easily learn the illusion over time. For SZs, both strength of
the illusion and the ability to learn the illusion over time are inconsistent.
The cognitive impairment in SZ impedes the learning process of the RHI, and SZs
are unable to utilize the repetition of the process as healthy individuals can.
PMID- 26443056
TI - No correlation between rates of suicidal ideation and completed suicides in
Europe: analysis of 49,008 participants (55+ years) based on the Survey of
Health, Ageing and Retirement in Europe (SHARE).
AB - BACKGROUND: Little is known about country-specific variations in suicidal
ideation (SID) by sex and how they correspond with completed suicide rate.
Therefore, the aim of the present study was to assess variations in SID
prevalence rates by sex and its correlation to completed suicide rates across
European countries. METHOD: SHARE is a cross-national European survey of
individuals over the age of 50 and their spouse of any age. The present study
relied on wave 4 conducted in 2010-2012 including 49,008 participants aged 55 to
104years from 16 countries. SID was evaluated using a single item from the Euro
D. Data on completed suicide rates were taken from the WHO mortality database.
RESULTS: Of the study population (n=49,008, 44.3% men, mean age 68.2+/-9.1years),
a total of 4139 (8.5%, 95% CI 8.2-8.7) reported suicidal ideation within the last
month. The women:men ratio in SID prevalence ranged from 1.30 in Estonia to 2.25
in Spain and Portugal. Regarding country-specific variation, the SID prevalence
patterns of both men and women did not correspond to the completed suicide rates
for males and females aged 55+ reported by the WHO (2013). Correlations were
rather moderate in men (r=0.45) and especially weak in women (r=0.16).
CONCLUSION: The study showed remarkable differences in SID prevalence by sex. The
most exciting finding was that SID rates did not correspond with completed
suicide rates in each country under investigation. However, the strength of these
patterns substantially differs across countries. This unexpected finding need to
be further evaluated.
PMID- 26443057
TI - Factor structure of the Bern Psychopathology Scale in a sample of patients with
schizophrenia spectrum disorders.
AB - BACKGROUND: The Bern Psychopathology Scale (BPS) is based on a system-specific
approach to classifying the psychopathological symptom pattern of schizophrenia.
It consists of subscales for three domains (language, affect and motor behaviour)
that are hypothesized to be related to specific brain circuits. The aim of the
study was to examine the factor structure of the BPS in patients with
schizophrenia spectrum disorders. METHODS: One hundred and forty-nine inpatients
with schizophrenia spectrum disorders were recruited at the Department of
Psychiatry II, Ulm University, Germany (n=100) and at the University Hospital of
Psychiatry, Bern, Switzerland (n=49). Psychopathology was assessed with the BPS.
The VARCLUS procedure of SAS((r)) (a type of oblique component analysis) was used
for statistical analysis. RESULTS: Six clusters were identified (inhibited
language, inhibited motor behaviour, inhibited affect, disinhibited affect,
disinhibited language/motor behaviour, inhibited language/motor behaviour) which
explained 40.13% of the total variance of the data. A binary division of
attributes into an inhibited and disinhibited cluster was appropriate, although
an overlap was found between the language and motor behaviour domains. There was
a clear distinction between qualitative and quantitative symptoms. CONCLUSIONS:
The results argue for the validity of the BPS in identifying subsyndromes of
schizophrenia spectrum disorders according to a dimensional approach. Future
research should address the longitudinal assessment of dimensional
psychopathological symptoms and elucidate the underlying neurobiological
processes.
PMID- 26443058
TI - Characterization of cross-linked immobilized arylesterase from Gluconobacter
oxydans 621H with activity toward cephalosporin C and 7-aminocephalosporanic
acid.
AB - Cross-linked enzyme aggregates (CLEAs) were prepared from several precipitant
agents using glutaraldehyde as a cross-linking agent with and without BSA,
finally choosing a 40% saturation of ammonium sulfate and 25 mM of
glutaraldehyde. The CLEAs obtained under optimum conditions were biochemically
characterized. The immobilized enzyme showed higher thermal activity and a
broader range of pH and organic solvent tolerance than the free enzyme.
Arylesterase from Gluconobacter oxydans showed activity toward cephalosporin C
and 7-aminocephalosporanic acid. The CLEAs had a Kcat/KM of 0.9 M(-1) /S(-1) for
7-ACA (7-aminocephalosporanic acid) and 0.1 M(-1) /S(-1) for CPC (cephalosporin
c), whereas free enzyme did not show a typical Michaelis-Menten kinetics.
PMID- 26443060
TI - wKinMut-2: Identification and Interpretation of Pathogenic Variants in Human
Protein Kinases.
AB - Most genomic alterations are tolerated while only a minor fraction disrupts
molecular function sufficiently to drive disease. Protein kinases play a central
biological function and the functional consequences of their variants are
abundantly characterized. However, this heterogeneous information is often
scattered across different sources, which makes the integrative analysis complex
and laborious. wKinMut-2 constitutes a solution to facilitate the interpretation
of the consequences of human protein kinase variation. Nine methods predict their
pathogenicity, including a kinase-specific random forest approach. To understand
the biological mechanisms causative of human diseases and cancer, information
from pertinent reference knowledge bases and the literature is automatically
mined, digested, and homogenized. Variants are visualized in their structural
contexts and residues affecting catalytic and drug binding are identified. Known
protein-protein interactions are reported. Altogether, this information is
intended to assist the generation of new working hypothesis to be corroborated
with ulterior experimental work. The wKinMut-2 system, along with a user manual
and examples, is freely accessible at http://kinmut2.bioinfo.cnio.es, the code
for local installations can be downloaded from https://github.com/Rbbt
Workflows/KinMut2.
PMID- 26443059
TI - Sgf73, a subunit of SAGA complex, is required for the assembly of RITS complex in
fission yeast.
AB - RNA interference (RNAi) is a widespread gene-silencing mechanism and is required
for heterochromatin assembly in a variety of organisms. The RNA-induced
transcriptional silencing complex (RITS), composed of Ago1, Tas3 and Chp1, is a
key component of RNAi machinery in fission yeast that connects short interference
RNA (siRNA) and heterochromatin formation. However, the process by which RITS is
assembled is not well understood. Here, we identified Sgf73, a subunit of the
SAGA co-transcriptional complex, is required for pericentromeric heterochromatin
silencing and the generation of siRNA. This novel role of Sgf73 is independent of
enzymatic activities or structural integrity of SAGA. Instead, Sgf73 is
physically associated with Ago1 and Chp1. The interactions among the subunits of
the RITS, including those between Tas3 and Chp1, between Chp1 and Ago1, between
Ago1 and Tas3, were all impaired by the deletion of sgf73(+). Consistently, the
recruitment of Ago1 and Chp1 to the pericentromeric region was abolished in
sgf73Delta cells. Our study unveils a moonlighting function of a SAGA subunit. It
suggests Sgf73 is a novel factor that promotes assembly of RITS and RNAi-mediated
heterochromatin formation.
PMID- 26443061
TI - Pigeons are resistant to experimental infection with H7N9 avian influenza virus.
AB - To determine the susceptibility of pigeons to the newly emerged avian influenza
virus subtype H7N9, we experimentally infected three different types of pigeons
(meat, town, and racing) with two different doses (2 * 10(4) or 2 * 10(5) EID50)
of H7N9 avian influenza virus A/Chicken/China/2013 by either intranasal and
intraocular inoculation (IN + IO) or intravenous injection (IV). In addition, the
potential transmission of H7N9 to pigeons by direct close contact with
experimentally infected pigeons and chickens was assessed. Results showed that
none of the experimentally infected pigeons exhibited any clinical signs
regardless of the infection route and dose. Of the 12 racing pigeons that were
randomly selected and necropsied, none of them had any gross lesions. In
agreement with this finding, virus was not isolated from all pigeons. No
detectable H7-specific antibodies were found in any pigeon. In contrast, 11 of 31
chickens that were either directly infected with H7N9 by IN + IO inoculation or
by contact with IN + IO-infected chickens had conjunctivitis. Virus was isolated
from all 31 chickens and H7-specific antibodies were detected in these chickens.
However, none of the IV-infected chickens or chickens in direct contact with IV
infected chickens had any clinical signs. No virus was isolated from these
chickens and no H7-specific antibody was detected. Overall, we conclude that
pigeons are less or not susceptible to the H7N9 virus at the doses used and are
not likely to serve as a reservoir for the virus. However, the virus does cause
conjunctivitis in chickens and can transmit to susceptible hosts by direct
contact.
PMID- 26443062
TI - Comparison of four molecular assays for the detection of Tembusu virus.
AB - Tembusu virus (TMUV) belongs to the genus Flavivirus that may cause severe egg
drop in ducks. In order to evaluate the most efficient TMUV detection method, the
performances of a conventional RT-PCR (C-RT-PCR), a semi-nested PCR (SN-RT-PCR),
a reverse-transcriptase real-time quantitative PCR (Q-RT-PCR), and a reverse
transcription loop-mediated isothermal amplification (RT-LAMP) targeting the TMUV
virus-specific NS5 gene were examined. In order to compare the sensitivity of
these four techniques, two templates were used: (1) plasmid DNA that contained a
partial region of the NS5 gene and (2) genomic RNA from TMUV-positive cell
culture supernatants. The sensitivities using plasmid DNA detection by C-RT-PCR,
SN-RT-PCR, Q-RT-PCR, and RT-LAMP were 2 * 10(4) copies/MUL, 20 copies/MUL, 2
copies/MUL, and 20 copies/MUL, respectively. The sensitivities using genomic RNA
for the C-RT-PCR, SN-RT-PCR, Q-RT-PCR, and RT-LAMP were 100 pg/tube, 100, 10, and
100 fg/tube, respectively. All evaluated assays were specific for TMUV detection.
The TMUV-specific RNA was detected in cloacal swabs from experimentally infected
ducks using these four methods with different rates (52-92%), but not in the
control (non-inoculated) samples. The sensitivities of RT-PCR, SN-RT-PCR, Q-RT
PCR, and RT-LAMP performed with cloacal swabs collected from suspected TMUV
infected ducks within 2 weeks of severe egg-drop were 38/69 (55.1%), 52/69
(75.4%), 57/69 (82.6%), and 55/69 (79.7%), respectively. In conclusion, both RT
LAMP and Q-RT-PCR can provide a rapid diagnosis of TMUV infection, but RT-LAMP is
more useful in TMUV field situations or poorly equipped laboratories.
PMID- 26443063
TI - Immunogenic and protective efficacy of recombinant protein GtxA-N against
Gallibacterium anatis challenge in chickens.
AB - Gallibacterium anatis is a major cause of reproductive tract infections in
chickens. Here, we aimed to evaluate the efficacy of the recombinant protein GtxA
N at protecting hens, by addressing three objectives; (i) evaluating the antibody
response following immunization (ii) scoring and comparing lesions, following
challenge with G. anatis, in immunized and non-immunized hens and (iii)
investigating if the anti-GtxA-N antibody titre in individual hens correlated
with the observed lesions. Two consecutive experiments were performed in hens. In
the first experiment hens were immunized with GtxA-N on day 0 and day 14,
infected with G. anatis on day 28 and euthanized on day 56. The GtxA-N antibody
response was assessed in pooled serum samples throughout the experiment, using an
indirect enzyme-linked immunosorbent assay (ELISA). In the second experiment the
GtxA-N antibody titres were assessed in individual hens before and after
immunization. Subsequently, the hens were inoculated with G. anatis and finally
all hens where euthanized and submitted for post mortem examination 48 h after
inoculation. Immunization elicited strong antibody responses that lasted at least
8 weeks (P < .0001). The individual antibody titres observed in response to
immunization varied considerably among hens (range: 174,100-281,500). Lesion
scores following G. anatis infection were significantly lower in immunized hens
compared to non-immunized hens (P = .004). Within the immunized group, no
correlation was found between the individual antibody titres and the lesion
scores. This study clearly demonstrated GtxA-N as a vaccine antigen able of
inducing protective immunity against G. anatis.
PMID- 26443064
TI - The contribution of aerobic and anaerobic respiration to intestinal colonization
and virulence for Salmonella typhimurium in the chicken.
AB - The basic mechanism whereby Salmonella serovars colonize the chicken intestine
remains poorly understood. Previous studies have indicated that proton
translocating proteins utilizing oxygen as terminal electron acceptor do not
appear to be of major importance in the gut of the newly hatched chicken and
consequently they would be even less significant during intestinal colonization
of more mature chickens where the complex gut microflora would trap most of the
oxygen in the lumen. Consequently, alternative electron acceptors may be more
significant or, in their absence, substrate-level phosphorylation may also be
important to Salmonella serovars in this environment. To investigate this we
constructed mutants of Salmonella enterica serovar Typhimurium defective in
various aspects of oxidative or substrate-level phosphorylation to assess their
role in colonization of the chicken intestine, assessed through faecal shedding,
and virulence. Mutations affecting use of oxygen or alternative electron
acceptors did not eliminate faecal shedding. By contrast mutations in either pta
(phosphotransacetylase) or ackA (acetate kinase) abolished shedding. The pta but
not the ackA mutation also abolished systemic virulence for chickens. An
additional ldhA (lactate dehydrogenase) mutant also showed poor colonizing
ability. We hypothesise that substrate-level phosphorylation may be more
important than respiration using oxygen or alternative electron acceptors for
colonization of the chicken caeca.
PMID- 26443066
TI - Intraoral digital impression for fabricating a replica of an implant-supported
interim prosthesis.
AB - Even though a customized scannable impression coping is used, the precise
replication of the emergent profile developed by an implant-supported interim
prosthesis (ISIP) is difficult. This article describes a method for overcoming
the limitations of a customized scannable impression coping. With this technique,
a customized scannable impression coping is eliminated, and the information from
an ISIP is obtained.
PMID- 26443067
TI - Effect of gingival displacement cord and cordless systems on the closure,
displacement, and inflammation of the gingival crevice.
AB - STATEMENT OF PROBLEM: The gingival sulcus should remain open long enough for the
impression material to flow into it and completely fill the space provided by the
gingival displacement. Impressions with less sulcal width have a higher incidence
of voids, tearing of impression materials, and reduction in marginal accuracy.
PURPOSE: The purpose of this clinical study was to investigate the closure,
gingival displacement, and gingival inflammation of the gingival crevice after
the use of medicated gingival displacement cord and cordless systems. MATERIAL
AND METHODS: Gingival sulcus closure was studied in 40 participants. They were
divided into 4 groups: 2 cord (Ultrapack, SilTrax AS) and 2 cordless (Expasyl,
Traxodent Hemodent paste) methods. The labial surfaces of the maxillary right and
left central incisors were evaluated. Gingival sulcus was photographed every 20
seconds from 0 to 180 seconds after the removal of the cord or cordless system.
The bleeding index (BI) and gingival index (GI) were measured at day 0, day 1,
and day 7. The width of the sulcal orifice was measured at the mid-buccal (MB)
and transitional line angle (TLA) on a digital image, using computer software
(Photoshop version 7.0; Adobe). Data were analyzed with ANOVA, Tukey honest
significant difference (HSD), Kruskal-Wallis, and Mann-Whitney U tests
(alpha=.05). RESULTS: All groups showed a sulcal width greater than 0.22 mm up to
60 seconds after the removal of the displacement materials at the MB and up to 40
seconds at the TLA. Among all groups, Expasyl showed the fastest closure.
Gingival displacement in the MB area for the cord group was greater than for the
cordless groups. GI and BI indices were larger for the cord group than for the
cordless group at days 0 and 1. CONCLUSIONS: At up to 60 seconds, the cord and
cordless techniques were equally effective. The cord group showed a greater
amount of displacement than the cordless group. However, the cordless materials
showed reduced frequency of changes to the gingival index.
PMID- 26443068
TI - Relationship between impact of maxillary anterior fixed prosthodontic
rehabilitation on daily living, satisfaction, and personality profiles.
AB - STATEMENT OF PROBLEM: Personality profiles may affect the impact of dental
treatment on daily living and patient satisfaction. PURPOSE: The purpose of this
clinical trial was to evaluate the impact of maxillary anterior fixed
prosthodontic rehabilitation on daily living and the satisfaction of patients and
to investigate its relationship with personality profiles. MATERIAL AND METHODS:
Fifty-nine participants (25 men and 34 women; mean age 32.4 +/- 6.9 years)
received maxillary anterior partial fixed dental prostheses. The clinical success
of the prostheses was evaluated following specific criteria. The Dental Impact on
Daily Living (DIDL) questionnaire was used to measure satisfaction with the
prostheses and their impact on daily living. The Neuroticism-Extraversion
Openness Five-Factor Inventory (NEO-FFI) was used to measure patients'
personality profiles. The paired sample t test was used to compare satisfaction
and personality scores before and after treatment (alpha=.05). RESULTS:
Participants' total satisfaction and their satisfaction with appearance, pain
tolerance, oral comfort, general performance, and eating improved after treatment
(P<.05). Before treatment, women were less satisfied with general performance
(P=.047) and scored higher on the Neuroticism score (P=.039); however, after
treatment, women were more satisfied with appearance (P=.004). Age and sex had no
significant correlation with personality profiles after treatment. Before
treatment, Neuroticism, Openness, and Conscientiousness scores were associated
with dental satisfaction and impact on daily life (P<.05). After treatment,
Neuroticism, Openness, and Extraversion scores were associated with dental
satisfaction and impact on daily life (P<.05). CONCLUSIONS: Patient satisfaction
with their oral condition improved after partial fixed dental prosthetic
rehabilitation in the maxillary anterior esthetic zone. Psychological profiles
(Neuroticism, Extraversion, Openness, and Conscientiousness) may be involved in
and explain the impact on daily living and the degree of patient satisfaction
with their prostheses.
PMID- 26443069
TI - Self-Relay Gold(I)-Catalyzed Pictet-Spengler/Cyclization Cascade Reaction for the
Rapid Elaboration of Pentacyclic Indole Derivatives.
AB - Gold-catalyzed cascade reactions allow the rapid elaboration of pentacyclic
indolo[2,3-a]quinolizidines from N-allyl tryptamines and ortho
alkynylarylaldehydes. The tandem process combines a gold-catalyzed Pictet
Spengler reaction and a cyclization occurring concomitantly with an allyl
transfer from the nitrogen atom to the stilbene function. Various substituted
allyls were successfully transferred, furnishing the products in yields typically
ranging from 60-98 % in high diastereoselectivity. Tryptamines bearing a butenol
chain undergo an additional cyclization to chiral hemiaminals in high
diastereoselectivities.
PMID- 26443070
TI - Cytomegalovirus immunodiagnostics: Getting closer to personalized cytomegalovirus
prevention?
PMID- 26443071
TI - Editorial: Looking back and also into the future of Acta Anaesthesiologica
Scandinavica.
PMID- 26443072
TI - Erratum.
AB - Kim SY, Huh KH, Roh YH, Oh YJ, Park J, Choi YS. Nefopam as an adjunct to
intravenous patient-controlled analgesia after renal transplantation: a
randomised trial. Acta Anaesthesiologica Scandinavica, 59(8), 1068-1075. DOI:
10.1111/aas.12519. In the article "Nefopam as an adjunct to intravenous patient
controlled analgesia after renal transplantation: a randomised trial", the
published title of vertical axis B in Figure 2 which is 'Pain at rest' was
incorrect. The correct title of the vertical axis B is 'Pain on coughing.' The
correct figure 2 has been reproduced here for clarity. We apologize for any
inconvenience caused.
PMID- 26443073
TI - Regulatory T cells induction by autologous mesenchymal stromal cells infusion in
kidney transplant: Does the 'immunosuppression' matter?
PMID- 26443074
TI - Arthrobacter sanguinis: an uncommon cause of peritonitis in a peritoneal dialysis
patient.
PMID- 26443075
TI - Analysis and characterization of anthocyanins and carotenoids in Japanese blue
tomato.
AB - Tomato (Solanum lycopersicum) is rich in anthocyanins, which are polyphenolic
pigments. This study aimed to analyze and characterize the anthocyanin
composition in cultivated blue tomato in Japan. The extracts of peel, seed, and
pulp of tomatoes were purified following which anthocyanins and lycopene contents
were analyzed using high-performance liquid chromatography and electrospray
ionization mass spectrometry. Eleven types of anthocyanins were identified,
including delphinidin, petunidin, and malvidin. Further, the antioxidant activity
of anthocyanins was evaluated using 2,2'-azino-bis-(3-ethylbenzthiazoline-6
sulfonic acid) diammonium salt radical quenching assays and electron spin
resonance. "Blue tomato" extracts exert antioxidant activity. Thus, we showed
that petunidin was present in the "blue tomato" peel while lycopene was present
in the peel and pulp. Additionally, the blue tomato peel extract was found to
significantly inhibit H2O2-induced cell death in vitro. This is the first study
on cell protective effects of Japanese blue tomato extract and petunidin in
murine photoreceptor cells.
PMID- 26443077
TI - Synthesis and characterization of a trans-1 hexakis-fullerene linker that forms
crystalline polymers with silver salts.
AB - A new flexible hexakis-fullerene adduct with two bis(pyridin-4-ylmethyl)malonate
groups located at trans-1 positions was synthesized. Via reaction with Ag(PF6)
under two different conditions, two new 1D coordination polymers were obtained;
under a nitrogen atmosphere, the silver ions are connected by argentophilic
interactions but under an ambient atmosphere, the silver ions exhibit no
interaction between them but coordination to the (H2PO4)(-) ions.
PMID- 26443076
TI - Rational Design of Benzylidenehydrazinyl-Substituted Thiazole Derivatives as
Potent Inhibitors of Human Dihydroorotate Dehydrogenase with in Vivo Anti
arthritic Activity.
AB - Human dihydroorotate dehydrogenase (hDHODH) is an attractive therapeutic target
for the treatment of rheumatoid arthritis, transplant rejection and other
autoimmune diseases. Based on the X-ray structure of hDHODH in complex with lead
compound 7, a series of benzylidenehydrazinyl-substituted thiazole derivatives as
potent inhibitors of hDHODH were designed and synthesized, of which 19 and 30
were the most potent with IC50 values in the double-digit nanomolar range.
Moreover, compound 19 displayed significant anti-arthritic effects and favorable
pharmacokinetic profiles in vivo. Further X-ray structure and SAR analyses
revealed that the potencies of the designed inhibitors were partly attributable
to additional water-mediated hydrogen bond networks formed by an unexpected
buried water between hDHODH and the 2-(2-methylenehydrazinyl)thiazole scaffold.
This work not only elucidates promising scaffolds targeting hDHODH for the
treatment of rheumatoid arthritis, but also demonstrates that the water-mediated
hydrogen bond interaction is an important factor in molecular design and
optimization.
PMID- 26443078
TI - Discovery of Selective Histone Deacetylase 6 Inhibitors Using the Quinazoline as
the Cap for the Treatment of Cancer.
AB - Novel selective histone deacetylase 6 (HDAC6) inhibitors using the quinazoline as
the cap were designed, synthesized, and evaluated for HDAC enzymatic assays. N
Hydroxy-4-(2-methoxy-5-(methyl(2-methylquinazolin-4-yl)amino)phenoxy)butanamide,
23bb, was the most potent selective inhibitor for HDAC6 with an IC50 of 17 nM and
showed 25-fold and 200-fold selectivity relative to HDAC1 and HDAC8,
respectively. In vitro, 23bb presented low nanomolar antiproliferative effects
against panel of cancer cell lines. Western blot analysis further confirmed that
23bb increased acetylation level of alpha-tubulin in vitro. 23bb has a good
pharmacokinetic profile with oral bioavailability of 47.0% in rats. In in vivo
efficacy evaluations of colorectal HCT116, acute myelocytic leukemia MV4-11, and
B cell lymphoma Romas xenografts, 23bb more effectively inhibited the tumor
growth than SAHA even at a 4-fold reduced dose or ACY-1215 at the same dose. Our
results indicated that 23bb is a potent oral anticancer candidate for selective
HDAC6 inhibitor and deserves further investigation.
PMID- 26443080
TI - The network organization of protein interactions in the spliceosome is reproduced
by the simple rules of food-web models.
AB - The network structure of biological systems provides information on the
underlying processes shaping their organization and dynamics. Here we examined
the structure of the network depicting protein interactions within the
spliceosome, the macromolecular complex responsible for splicing in eukaryotic
cells. We show the interactions of less connected spliceosome proteins are nested
subsets of the connections of the highly connected proteins. At the same time,
the network has a modular structure with groups of proteins sharing similar
interaction patterns. We then investigated the role of affinity and specificity
in shaping the spliceosome network by adapting a probabilistic model originally
designed to reproduce food webs. This food-web model was as successful in
reproducing the structure of protein interactions as it is in reproducing
interactions among species. The good performance of the model suggests affinity
and specificity, partially determined by protein size and the timing of
association to the complex, may be determining network structure. Moreover,
because network models allow building ensembles of realistic networks while
encompassing uncertainty they can be useful to examine the dynamics and
vulnerability of intracelullar processes. Unraveling the mechanisms organizing
the spliceosome interactions is important to characterize the role of individual
proteins on splicing catalysis and regulation.
PMID- 26443081
TI - New insights to lateral rooting: Differential responses to heterogeneous nitrogen
availability among maize root types.
AB - Historical domestication and the "Green revolution" have both contributed to the
evolution of modern, high-performance crops. Together with increased irrigation
and application of chemical fertilizers, these efforts have generated sufficient
food for the growing global population. Root architecture, and in particular root
branching, plays an important role in the acquisition of water and nutrients,
plant performance, and crop yield. Better understanding of root growth and
responses to the belowground environment could contribute to overcoming the
challenges faced by agriculture today. Manipulating the abilities of crop root
systems to explore and exploit the soil environment could enable plants to make
the most of soil resources, increase stress tolerance and improve grain yields,
while simultaneously reducing environmental degradation. In this article it is
noted that the control of root branching, and the responses of root architecture
to nitrate availability, differ between root types and between plant species.
Since the control of root branching depends upon both plant species and root
type, further work is urgently required to determine the appropriate genes to
manipulate to improve resource acquisition by specific crops.
PMID- 26443079
TI - Kinases as druggable targets in trypanosomatid protozoan parasites.
PMID- 26443082
TI - Metastable orientational order of colloidal discoids.
AB - The interplay between phase separation and kinetic arrest is important in
supramolecular self-assembly, but their effects on emergent orientational order
are not well understood when anisotropic building blocks are used. Contrary to
the typical progression from disorder to order in isotropic systems, here we
report that colloidal oblate discoids initially self-assemble into short,
metastable strands with orientational order-regardless of the final structure.
The model discoids are suspended in a refractive index and density-matched
solvent. Then, we use confocal microscopy experiments and Monte Carlo simulations
spanning a broad range of volume fractions and attraction strengths to show that
disordered clusters form near coexistence boundaries, whereas oriented strands
persist with strong attractions. We rationalize this unusual observation in light
of the interaction anisotropy imparted by the discoids. These findings may guide
self-assembly for anisotropic systems in which orientational order is desired,
such as when tailored mechanical properties are sought.
PMID- 26443083
TI - Fishing the targets of myeloid malignancies in the era of next generation
sequencing.
AB - Recent advent in next generation sequencing (NGS) and bioinformatics has
generated an unprecedented amount of genetic information in myeloidmalignancies.
This information may shed lights to the pathogenesis, diagnosis and
prognostication of these diseases and provide potential targets for therapeutic
intervention. However, the rapid emergence of genetic information will quickly
outpace their functional validation by conventional laboratory platforms.
Foundational knowledge about zebrafish hematopoiesis accumulated over the past
two decades and novel genomeediting technologies and research strategies in
thismodel organismhavemade it a unique and timely research tool for the study of
human blood diseases. Recent studies modeling human myeloid malignancies in
zebrafish have also highlighted the technical feasibility and clinical relevance
of thesemodels. Careful validation of experimental protocols and standardization
among laboratorieswill further enhance the application of zebrafish in the
scientific communities and provide important insights to the personalized
treatment ofmyeloid malignancies.
PMID- 26443084
TI - Monitoring communication with patients: analyzing judgments of satisfaction
(JOS).
AB - Medical students struggle to put into practice communication skills learned in
medical school. In order to improve our instructional designs, better insight
into the cause of this lack of transfer is foundational. We therefore explored
students' cognitions by soliciting self-evaluations of their history-taking
skills, coined 'judgments of satisfaction (JOSs)'. Our cognitive-psychological
approach was guided by Koriat's cue-utilization framework (J Exp Psychol Gen
126:349-370. doi: 10.1037/0096-3445.126.4.349 , 1997) which rests on the
assumption that internal and external cues inform learners' metacognitive
judgments, which, in turn, steer their actions. Judgments based on unsuitable
cues will cause ineffective behavior. Consequently, students are unable to
adequately master these skills or properly apply them in similar situations. For
the analysis, we had 524 medical undergraduates select scenes they were satisfied
or dissatisfied with from their video-recorded simulated-patient encounters and
explain why. Twenty transcripts were sampled for directed content analysis. We
found that approximately one-third of students' judgments focused on content (JOS
type-a); about half on the quality of the communication skills (JOS-type-b); and
about ten percent targeted the appropriateness of the skills harnessed (JOS-type
c). This lack of reflection on appropriateness may explain why students
experience problems adapting to new situations. It was primarily high-performance
students who formed type-c judgments; poor performers tended to give type-a and
type-b judgments. Future research would benefit from the use of our modified
version of Koriat's framework in order to further explore how high and poor
performing medical students differ in the way they form JOSs during
communications skills training.
PMID- 26443085
TI - Critical review: medical students' motivation after failure.
AB - About 10 % of students in each years' entrants to medical school will encounter
academic failure at some stage in their programme. The usual approach to
supporting these students is to offer them short term remedial study programmes
that often enhance approaches to study that are orientated towards avoiding
failure. In this critical review I will summarise the current theories about
student motivation that are most relevant to this group of students and describe
how they are enhanced or not by various contextual factors that medical students
experience during their programme. I will conclude by suggesting ways in which
support programmes for students who have encountered academic failure might be
better designed and researched in the future.
PMID- 26443087
TI - The First Published Case Report of an Adult Woman Who Developed Suicidal Ideation
as an Adverse Event Related to Methylphenidate Use.
PMID- 26443086
TI - Knowingly not wanting to know: Discourses of people diagnosed with mild cognitive
impairment.
AB - Mild cognitive impairment is a heterogeneous clinical state whereby assessed
cognitive changes over time may progress to dementia, remain stable or revert to
back to normal. This study aimed to identify, through discourse analysis, how
people with a diagnosis of mild cognitive impairment used language in order to
reveal the societal views and shared meanings of the diagnosis, and the positions
taken by people. Seven people with mild cognitive impairment were interviewed,
and three discourses emerged during analysis. One of the discourses revealed was
'Not Knowing' about mild cognitive impairment. Furthermore, in the absence of a
coherent discourse related to mild cognitive impairment, participants went on to
position themselves between two more familiar discourse; 'Knowing' about ageing
and dying and 'Not Wanting to Know' about dementia. Clinicians must consider how
information is presented to people about mild cognitive impairment, including
where mild cognitive impairment is positioned in respect to normal ageing and
dementia.
PMID- 26443088
TI - Impact of cancer on the effectiveness of cardiac Troponin I to predict right
ventricular dysfunction in acute pulmonary embolism.
AB - BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are connected
with a poor outcome in cancer patients. We aimed to investigate the impact of
cancer on the effectiveness of cardiac Troponin I (cTnI) to predict right
ventricular dysfunction (RVD) in acute PE. METHODS: We retrospectively analyzed
the data of 182 patients with confirmed PE. PE patients were subdivided into two
groups: (i) with concomitant active cancer disease or history of cancer, and (ii)
without known cancer. Receiver operating characteristic (ROC) curves with area
under the curve (AUC) was calculated for cTnI predicting RVD and related cut-off
levels for both groups. RESULTS: Thirty-seven PE patients (20.3%) had an active
cancer disease or a history of cancer. In contrast, 145 (79.7%) of the included
PE patients did not have a known cancer disease or a history of cancer. In the PE
group with cancer, analysis of the ROC curve showed an AUC of 0.76 for cTnI
predicting RVD with an optimal cut-off value of 0.04 ng/mL; the risk of
misclassification was 25.0%. In the PE group without cancer, AUC was 0.81 for
cTnI predicting RVD with an optimal cut-off value of 0.015 ng/mL; the risk of
misclassification was 24.9%. CONCLUSIONS: cTnI is effective for predicting RVD in
PE patients with and without cancer. However, the effectiveness of cTnI to
predict RVD was higher in PE patients without cancer than in those with cancer or
a history of cancer.
PMID- 26443089
TI - Helicobacter cinaedi knee infection after arthroscopy in an immunocompetent
patient.
AB - An otherwise healthy 36-year-old man was hospitalised due to a traumatic tear of
the meniscus in the left knee. An arthroscopy was performed and his meniscus was
partially resected. Thirty days later, he was rehospitalised with arthritis in
the left knee and cellulitis on the left tibia. Helicobacter cinaedi was isolated
from the synovial fluid, which was incubated in a BACTEC Paediatric bottle. The
patient was treated with oral rifampicin and moxifloxacin for 6 weeks with good
clinical response without relapse. The source of the infection was not found. The
case emphasises the importance of incubating the synovial fluid in a rich medium
such as a BACTEC Peds Plus/F bottle. Physicians and microbiologists should be
aware of H. cinaedi as a human pathogen causing a range of disease
manifestations, including infective arthritis and cellulitis, particularly if
symptoms evolve in the weeks following a surgical procedure.
PMID- 26443090
TI - Acute appendicitis presenting as pneumoperitoneum in a teenage boy undergoing
chemotherapy.
AB - Chemotherapy of paediatric haematological malignancies can induce infectious
complications of the gastrointestinal tract, with predilection of the ileocaecal
region. Common causes of right lower abdominal pain in the febrile patient with
neutropaenia include acute appendicitis, typhlitis, ileus and intussusception. In
this case report, we describe a teenage boy with acute appendicitis presenting
with pneumoperitoneum during his course of chemotherapy. The incidence,
aetiology, diagnosis, investigations and management of this uncommon presentation
in a common disease are discussed. The controversial topic of the management of
acute appendicitis in a febrile patient with neutropaenia is also reviewed and
discussed.
PMID- 26443091
TI - Neonatal small left colon syndrome.
PMID- 26443092
TI - A 75-year-old woman with acquired haemophilia disguised by warfarin treatment.
AB - Acquired haemophilia is a rare coagulation disorder more commonly seen in elderly
patients. Diagnosis and effective treatment can be delayed if patients are on
warfarin treatment, as the bleeding symptoms may be erroneously attributed to
this agent. We present a case report of a 75-year-old woman whose unexplained,
severe and persistent bleeding was treated with surgical decompression and plasma
transfusions, an appropriate management based on the assumption that warfarin was
the cause of the bleeding. It was only when the patient's international
normalised ratio returned to normal that a persistent abnormal activated partial
thromboplastin time was noted. This delayed the correct diagnosis and treatment.
Awareness of acquired haemophilia as a possible cause of sudden bleeding should
be encouraged, and the wider dissemination of any relevant experience of similar
cases would also be welcome.
PMID- 26443093
TI - Paediatric trauma with hyperamylasemia.
AB - In this case report, we describe a paediatric case of hyperamylasemia following
parotid trauma. A 12-year-old boy was hit by a motorcycle, sustaining only
superficial lacerations to the face overlying the parotid. A hyperamylasemia was
noted, and further characterised by a fractionated isoamylase test, as being
predominantly of the salivary type. Serum lipase levels were low. Based on these
investigations, pancreatic injury was judged unlikely with the minor parotid
trauma being the probable source of the hyperamylasemia. The patient was spared
further unnecessary investigations and managed conservatively.
PMID- 26443094
TI - An unusual inguinoscrotal hernia with renal involvement.
AB - We present a case of a 74-year-old man who, while in intensive treatment unit for
an upper gastrointestinal bleed, decompensated cardiac failure and concurrent
pneumonia, was found to have a large right hydronephrotic pelvic kidney and
bladder within the hernia. After discharge, he was medically optimised for 7
months before undergoing an elective open mesh repair of his hernia. During the
procedure, drainage of a large hydrocoele was performed to facilitate reduction
of the hernia. Postoperatively, he underwent ureteric stenting due to a
persistent hydronephrosis with impairment of his renal function. He subsequently
made a good recovery and was discharged home with outpatient follow-up planned.
PMID- 26443096
TI - Severe bone and mineral disease in an adolescent with chronic kidney disease: a
case from the 70s?
PMID- 26443095
TI - Multiple embolic cerebral infarcts as the first manifestation of metastatic
ovarian cancer.
AB - A 36-year-old woman presented to the emergency department with a 3-day history of
an occipital headache associated with transient visual impairment and short-term
memory loss. MRI of the brain showed innumerable focal embolic infarcts of
differing ages, for which a cause could not be determined. The patient was
discharged and readmitted 7 weeks later with acute aphasia and a right-sided
hemiplegia. CT of the abdomen revealed a right-sided ovarian mass and prominent
retroperitoneal nodes, which cytology confirmed to be metastatic ovarian cancer.
PMID- 26443097
TI - Reversed ocular ischaemic syndrome secondary to carotid cavernous sinus
embolisation.
AB - Ocular ischaemic syndrome is a progressive and serious vision-threatening
condition that is usually associated with carotid artery disease, and poor
effective therapeutic options are available. In the present case, a 65-year-old
woman was submitted to embolisation of spontaneous carotid-cavernous fistula with
complete resolution of initial ophthalmoplaegia and ocular hypertension. Later,
ocular ischaemia was detected. Cerebral angiography showed delayed choroidal
flush and the patient was admitted for hypervolaemic hypertension therapy and
medicated with nimodipine. The ischaemia was reversed and visual function
improved.
PMID- 26443098
TI - Tuberculous pseudoaneurysm of the ascending aorta.
AB - Increase in the incidence of drug resistance and association with HIV has led to
a resurgence of tuberculosis. However, tubercular arteritis continues to remain a
rare entity with a prelidection for the thoracic aorta. We report a tubercular
ascending aortic pseudoaneurysm in a patient already on treatment for
disseminated tuberculosis who underwent successful surgical repair and also
review literature pertaining to this entity.
PMID- 26443099
TI - Iron-induced gastric ulceration with radiological and endoscopic appearance of
carcinoma.
AB - Erosive injury of the upper gastrointestinal tract resulting from therapeutic
oral iron supplements is an uncommon phenomenon. We present a case of a large
gastric ulcer with clinical, endoscopic and radiological features suggestive of
malignancy, which resolved completely on cessation of iron therapy.
PMID- 26443100
TI - Acute myeloid leucaemia with trisomy 14 as a sole cytogenetic abnormality.
PMID- 26443101
TI - Short-term outcomes following elective transcatheter arterial embolization for
splenic artery aneurysms: data from a nationwide administrative database.
AB - BACKGROUND: Splenic artery aneurysm (SAA) rupture is life-threatening. Although
elective transcatheter arterial embolization (TAE) suggested low in-hospital
death in previous studies, there has been no large multi-center study of elective
TAE for SAA. PURPOSE: To examine the short-term outcomes of TAE for splenic
artery aneurysm (SAA) and analyze the factors associated with the outcomes,
including liver cirrhosis, using a nationwide administrative inpatient database.
MATERIAL AND METHODS: We identified patients who received elective TAE with a
principal diagnosis of SAA. We assessed the patient background characteristics,
comprising age, sex, and specific co-morbidities, including liver cirrhosis. The
outcomes included the rate of TAE-related complications (acute pancreatitis,
splenic infarction, splenic abscess, or intraperitoneal hematoma), length of
stay, and in-hospital mortality. RESULTS: Among 18.3 million inpatients in the
database between July 2010 and March 2013, we identified 534 patients who
received elective TAE for SAA at 229 participating hospitals. Fifty-four (10.1%)
patients had liver cirrhosis. No in-hospital deaths were observed. Thirty-two
(6.0%) patients had at least one TAE-related complication. A multivariate linear
regression analysis revealed that liver cirrhosis was significantly associated
with longer length of stay (9.5 days; 95% confidence interval [CI], 7.0-12.0
days; P < 0.001). A logistic regression analysis showed that liver cirrhosis was
not significantly associated with TAE-related complications (odds ratio, 0.99;
95% CI, 0.29-3.39; P = 0.980). CONCLUSION: The results revealed no in-hospital
mortality and a low complication rate associated with elective TAE for SAA
including liver cirrhosis patients.
PMID- 26443102
TI - Surface engineering for an enhanced photoelectrochemical response of TiO2
nanotube arrays by simple surface air plasma treatment.
AB - A simple method to improve the photoelectrochemical performance of TiO2 nanotube
arrays (NTs) by simple air plasma post-treatment is reported. The air plasma
treated sample shows higher photocurrent density and incident photo current
efficiency with high stability, about 3-4 times that of the pristine TiO2 NTs
even after six months.
PMID- 26443103
TI - A DFT study of adsorption of imidazole, triazole, and tetrazole on oxidized
copper surfaces: Cu2O(111) and Cu2O(111)-w/o-CuCUS.
AB - Azoles and their derivatives are known for their corrosion inhibition ability for
copper. For this reason the bonding of imidazole, triazole, and tetrazole-used as
archetypal models of azole corrosion inhibitors-to Cu2O(111) and Cu2O(111)-w/o
Cu(CUS) was characterized using density functional theory (DFT) calculations. The
former surface contains coordinatively-saturated (CSA) and coordinatively
unsaturated (CUS) Cu sites, whereas the latter lacks the CUS sites. We find that
the molecules preferentially bond with a single unsaturated N atom to a surface
Cu ion and concomitantly form a hydrogen bond with the surface O ion. They adsorb
rather strongly at CUS sites with an adsorption energy of about -1.6 eV (as
calculated with the PBE functional), whereas the bonding at CSA sites is about
three times weaker thus being similar as on metallic Cu(111). The impact of van
der Waals dispersion interactions on molecular adsorption bonding is also
addressed. Depending on specifics of the adsorption structure, they strengthen
the adsorption bonding by about 0.2-0.5 eV. Due to this specific bonding
enhancement, dispersion interactions alter the relative stability of adsorption
modes for tetrazole. An atomistic thermodynamics approach was used to construct
two-dimensional phase diagrams for all the three molecules. In the viable range
of oxygen chemical potential only three phases appear in the phase-diagrams, two
of which are the high coverage (1 * 1) molecular phases (one on Cu2O(111) and the
other on Cu2O(111)-w/o-Cu(CUS)) and the third is clean Cu2O(111)-w/o-Cu(CUS). The
current results indicate that molecular adsorption at CUS sites is strong enough
to compensate the thermodynamic deficiency of stoichiometric Cu2O(111) thus
making it more stable than Cu2O(111)-w/o-Cu(CUS), unless the conditions are too
oxygen rich and/or for azole lean. This finding may tentatively suggest that the
corrosion inhibition capability of azoles stems from their ability to passivate
reactive surface sites.
PMID- 26443104
TI - Revisiting the chlorophyll biosynthesis pathway using genome scale metabolic
model of Oryza sativa japonica.
AB - Chlorophyll is one of the most important pigments present in green plants and
rice is one of the major food crops consumed worldwide. We curated the existing
genome scale metabolic model (GSM) of rice leaf by incorporating new compartment,
reactions and transporters. We used this modified GSM to elucidate how the
chlorophyll is synthesized in a leaf through a series of bio-chemical reactions
spanned over different organelles using inorganic macronutrients and light
energy. We predicted the essential reactions and the associated genes of
chlorophyll synthesis and validated against the existing experimental evidences.
Further, ammonia is known to be the preferred source of nitrogen in rice paddy
fields. The ammonia entering into the plant is assimilated in the root and leaf.
The focus of the present work is centered on rice leaf metabolism. We studied the
relative importance of ammonia transporters through the chloroplast and the
cytosol and their interlink with other intracellular transporters. Ammonia
assimilation in the leaves takes place by the enzyme glutamine synthetase (GS)
which is present in the cytosol (GS1) and chloroplast (GS2). Our results provided
possible explanation why GS2 mutants show normal growth under minimum
photorespiration and appear chlorotic when exposed to air.
PMID- 26443105
TI - The champagne toast position isolates the supraspinatus better than the Jobe
test: an electromyographic study of shoulder physical examination tests.
AB - BACKGROUND: While Jobe's test is widely used, it does not isolate supraspinatus
activity. Our purpose was to examine the electromyographic (EMG) activity within
the supraspinatus and deltoid with resisted abduction to determine the shoulder
position that best isolates the activity of the supraspinatus. METHODS: We
performed EMG analysis of the supraspinatus, anterior head of the deltoid, and
middle head of the deltoid in 10 normal volunteers. We measured EMG activity
during resisted shoulder abduction in the scapular plane to both manual
resistance and a standardized load in varying degrees of abduction and rotation.
To determine which position best isolates supraspinatus activity, the ratio of
supraspinatus to deltoid activity (S:D) was calculated for each position. Results
were analyzed with a repeated-measures analysis of variance with Bonferroni
correction. The posterior deltoid was excluded as it serves mostly to extend and
externally rotate. RESULTS: Our study confirmed Jobe's findings of maximal
supraspinatus activity at 90 degrees of abduction. However, decreasing abduction
significantly increased S:D for both resisted manual testing and testing against
a standardized load (P = .002 and .001, respectively). The greatest S:D ratio
(4.6 +/- 3.4 for standardized load testing) was seen at the "champagne toast"
position, i.e., 30 degrees of abduction, mild external rotation, 30 degrees of
flexion, and 90 degrees of elbow flexion. The smallest ratio (0.8 +/- 0.6) was
seen at Jobe's position. CONCLUSIONS: Testing of abduction strength in the
champagne toast position, i.e., 30 degrees of abduction, mild external rotation,
and 30 degrees of flexion, better isolates the activity of the supraspinatus
from the deltoid than Jobe's "empty can" position.
PMID- 26443106
TI - Long-term outcome of tuberoplasty for irreparable massive rotator cuff tears: is
tuberoplasty really applicable?
AB - BACKGROUND: Tuberoplasty is a therapeutic option for irreparable massive rotator
cuff tear (RCT). However, no study has reported long-term outcomes after
arthroscopic tuberoplasty. METHODS: We evaluated 16 patients who underwent
arthroscopic tuberoplasty for symptomatic irreparable massive RCT without
pseudoparalysis. Patients were a mean age of 64 years (range, 43-80 years) at the
time of the operation, and the mean duration of follow-up was 98 months (range,
84-126 months). RESULTS: At the last follow-up, the visual analog scale score for
pain during motion had decreased to 2.3 from a preoperative mean of 6.9 (P <
.001). The mean University of California at Los Angeles and Constant scores
improved from 10.3 and 37.9 preoperatively to 27.2 and 59.2, respectively, at the
last follow-up (P < .001 for both). The best University of California at Los
Angeles (UCLA) and Constant scores during the follow-up duration were 28.3 and
60.3, respectively, at 5 years. The mean acromiohumeral interval changed from 5
mm preoperatively to 4 mm at the last follow-up. The rate of continuity in the
inferior scapulohumeral line decreased significantly from 69% (11 shoulders)
preoperatively to 19% (3 shoulders) at the last follow-up (P = .011). Only 1
patient underwent revision surgery. CONCLUSIONS: Arthroscopic tuberoplasty
yielded satisfactory outcomes during a mean 8-year follow-up period. Although
superior migration of the humeral head progressed with time, the clinical
outcomes were not affected. Arthroscopic tuberoplasty is a good option for
relieving pain and improving functionality in nonpseudoparalytic patients with
painful irreparable massive RCT.
PMID- 26443107
TI - Response to Jani et al. A prospective, randomized, doubleblind, multicentre,
parallel-group, active controlled study to compare efficacy and safety of
biosimilar adalimumab (Exemptia; ZRC-3197) and adalimumab (Humira) in patients
with rheumatoid arthritis.
PMID- 26443108
TI - Next generation sequencing and the next generation: how genomics is
revolutionizing reproduction.
PMID- 26443109
TI - Polyethyleneimine-associated polycaprolactone-Superparamagnetic iron oxide
nanoparticles as a gene delivery vector.
AB - This study describes the synthesis of novel gene delivery vector with low
toxicity and high transfection efficiency for magnetofection. The rational design
of magnetofection vector called PPMag (PEI-associated polycaprolactone (PCL)
SPIONs) composed of oleic acid (OA) stabilized superparamagnetic iron oxide
nanoparticles (SPPIONs) prepared by thermolysis of iron oleate with a combination
of hydrophobic PCL and proton absorbing polymer polyethyleneimine (PEI) (PEI-PCL
SPIONs) is described. Encapsulation of amphiphilic PEI with SPIONs not only
improves water dispersity of SPIONs, but also allows nucleic acid (NA)
condensation and endosomal/lysosomal escape via proton sponge effect after
internalization in cells. MTT cytotoxicity assay showed that cell viability was
improved compared to conventional PEI-SPIONs. The luciferase activity of magneto
polyplexes treated cells significantly improved compared to both controls
revealed that transfection efficiency of PPMag- pCIKlux polyplexes group was
improved compared to naked pCIKlux group. The application underneath of a rare
earth magnet significantly improve the transfection efficiency (i.e., the
luciferase activity doubles) compared to cells without magnet, indicating that
sedimentation induced by magnetic field plays important role in accumulation of
magneto-polyplexes on cell surfaces. The results demonstrate that PPMag can be
used as a novel gene transfection vector to improve transfection efficiency. (c)
2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 145
154, 2017.
PMID- 26443110
TI - Pretreating porcine sperm with lipase enhances developmental competence of
embryos produced by intracytoplasmic sperm injection.
AB - Intracytoplasmic sperm injection (ICSI) has been widely applied in humans, mice,
and some domestic animals to cure human infertility, or produce genetically
superior or genetically engineered animals. However, the production efficiency of
ICSI in pigs remains quite low. In this study, we developed a new sperm
pretreatment method to improve production efficiency of ICSI in pigs. Experiment
1 revealed that pretreating porcine sperm with 2.5 mg/ml lipase before ICSI
operation, not only can reduce the adhesion between sperm and the injection
pipette without adding polyvinylpyrrolidone (PVP) in the operating medium, but
also significantly improve male pronuclei (MPN) formation rate (55.56% vs. 40.00%
(0 mg/ml), 42.59% (5.0 mg/ml), 40.00% (10.0 mg/ml), P < 0.05) and enhance
developmental competence of ICSI embryos (26.03% vs. 10.87% (0 mg/ml), 10.00%
(5.0 mg/ml), 10.13% (10.0 mg/ml), P < 0.05). Experiment 2 showed that this method
has a higher MPN formation rate (50.47% vs. 30.78%, P < 0.05) and blastocyst rate
(18.81% vs. 7.41%, P < 0.05) than the PVP method, and was better than the Triton
X-100 treatment method (50.47% vs. 46.23%, 18.81% vs. 12.75%). Therefore,
pretreating porcine sperm with 2.5 mg/ml lipase before ICSI operation is highly
recommended, instead of adding PVP in the operating medium.
PMID- 26443111
TI - Erratum: Nanometre-scale probing of spin waves using single electron spins.
PMID- 26443112
TI - [Mechanical ileus in children with no prior history of abdominal surgery].
AB - In children with no prior history of abdominal surgery and no signs of
intussusception or incarcerated inguinal hernia, mechanical ileus may have a
congenital cause such as malrotation with volvulus or a persistent
omphalomesenteric duct. Acquired causes include sigmoid volvulus. We present two
cases of mechanical ileus in children. The first case involved a 6-year-old boy
who presented with acute abdominal pain and vomiting. An emergency laparotomy was
performed, with resection of the omphalomesenteric duct. Recovery was uneventful.
The other case concerned a 9-year-old boy who presented with increasing abdominal
pain, bilious vomiting and general clinical deterioration. An emergency
laparotomy was performed, revealing malrotation with volvulus and intestinal
ischaemia. Children with no prior abdominal history who present with symptoms
that may be caused by mechanical obstruction should be managed with a view to
surgery and without delay, in order to prevent a catastrophic outcome resulting
from a congenital or acquired mechanical obstruction.
PMID- 26443113
TI - [Unusual causes of hyperprolactinaemia].
AB - Pituitary adenoma is the main cause of hyperprolactinaemia; however, physicians
should be aware that the pituitary is not always to blame. There are many other
physiological and pathological causes for hyperprolactinaemia, and the
contribution of stress, medication and the presence of macroprolactin should not
be overlooked. We describe three patients - a 19-year-old female, a 28-year-old
female and a 20-year-old male - in whom hyperprolactinaemia was due to medication
use, physical stimulation of the nipple and a combination of macroprolactianaemia
with a microadenoma, respectively. The first two case reports show that
conducting a thorough patient history can prevent unnecessary imaging and
laboratory costs. The third case illustrates that macroprolactinaemia and true
hyperprolactinaemia may coexist. While early screening for macroprolactinaemia in
an asymptomatic patient can save money, finding macroprolactinaemia in a
symptomatic patient still warrants further workup.
PMID- 26443114
TI - [A pitfall in the treatment of hypothyroidism].
AB - Primary hypothyroidism is a disease commonly encountered by GPs and internal
medicine doctors. It is treated with levothyroxine, the synthetic T4 hormone. If
a patient with primary hypothyroidism suddenly requires higher dosages the reason
for this should be investigated. Common causes are drug-interactions, pregnancy
or non-compliance. Nevertheless, if a patient has other symptoms such as oedema
or unexpected weight gain, nephrotic syndrome should be considered. Urinalysis
can be very helpful in this. Thyroxin binds to plasma albumin, high levels of
which are excreted in patients with nephrotic syndrome. This paper presents two
patients, a 45-year-old male and a 72-year-old male, with primary hypothyroidism
who due to nephrotic syndrome required large amounts of levothyroxine.
PMID- 26443115
TI - [Ten tips for optimising your handover].
AB - Patient handover is of major importance for continuity of care and contributes to
patient safety. According to Joint Commission International (JCI), an American
quality institute, 67% of medical errors result from miscommunication. More than
half of these errors appear to be attributable to poor medical handover. JCI and
the World Health Organisation recommend standardising handover and training
doctors in order to improve the quality of medical handover. Little attention is
paid to handover as an essential medical competence during training to become a
doctor or medical specialist. Many hospitals lack either training or a
standardised format for handover. In this paper we discuss 10 tips for improving
the quality of intradisciplinary handover.
PMID- 26443116
TI - [Suicidality and alcohol abuse].
AB - This article describes the role played by a patient's mental competency in the
assessment and treatment of patients who are under the influence of alcohol and
expressing suicidal thoughts. The factors that should be taken into consideration
in the assessment of suicidality are not always clear: somatic complications or
possible discharge from the emergency room. The treating physician at the
emergency department should evaluate the mental competency. The risk of suicide
should also be assessed by a psychiatrist. In order to make the right decisions
about treatment and mental competency, the key concepts of proportionality,
effectiveness and subsidiarity in the assessment of mental competency are
crucial. These concepts require a personalized, multidisciplinary approach and
result in unique decisions which may differ from case to case. In the assessment
and treatment of patients under the influence of alcohol who are suicidal and do
not want to have a proper medical evaluation, communication between the emergency
physician, internist and psychiatrist is crucial to optimize both evaluation and
treatment. In this context, tasks and responsibilities should be clearly defined
in order to minimize the risk of errors and complications.
PMID- 26443117
TI - [Two travellers returning from the tropics with persistent wounds on their feet].
AB - Two young tropical medicine residents returned from Zanzibar with multiple aching
wounds on their toes that did not heal within 6 weeks. The clinical picture fit
'tungiasis', which is caused by Tunga penetrans, also known as jigger or
sandflea. The ectoparasites were surgically removed and the status of tetanus
vaccination was checked.
PMID- 26443118
TI - [Pneumomediastinum: intervention is not always necessary].
AB - Pneumomediastinum is characterized by the presence of free air in the
mediastinum. This can be a sign of a severe underlying disorder that requires
urgent intervention. However, pneumomediastinum is also associated with other
causes that can be treated conservatively. Here, we describe three patients who
presented with a primary or spontaneous pneumomediastinum and a secondary
pneumomediastinum due to traumatic or iatrogenic perforation. Recognition of the
underlying cause of pneumomediastinum is essential for further diagnostic studies
and patient management. Unnecessary investigations and interventions, which may
cause further harm to and hospitalization of the patient, can thereby be
prevented.
PMID- 26443119
TI - [A man with a painful hand after punching a wall].
AB - A 23-year-old man had a painful right hand after punching a wall. The base of the
second metacarpal was swollen and painful. The base of the second metacarpal is
difficult to assess radiologically, due to overlying structures. After a trauma,
additional slight oblique X-rays may help to make a diagnosis.
PMID- 26443120
TI - [A child with substantially itchy bumps on the back].
AB - A 2-year-old boy showed itchy papules and wheals, which were diagnosed as papular
urticaria. Papular urticaria are a hypersensitivity reaction after insect bites.
The condition can relapse even without the presence of insects or new bites.
Topical steroids or antihistamines diminish the symptoms in some cases.
PMID- 26443121
TI - Shifting the light emitting component from core to shell: an effective approach
to improve the efficiency of light-emitting diodes based on multi-junction
quantum materials.
AB - Herein, using the light emitting component as the inner shell, we construct an
advanced quantum-dot-quantum-well structure, ZnCdS/CdSe/CdZnSeS/ZnS, and use it
for the fabrication of a light-emitting-diode. In comparison with the device
containing conventional structured quantum dots, CdSe/CdZnSeS/ZnS, the advanced
device possesses a superior performance in aspects of luminance, current
efficiency, turn-on voltage and emitting wavelength tunability. Therefore, this
paper indicates a promising strategy for the fabrication of light emitting
devices based on quantum materials.
PMID- 26443122
TI - Spanish Implantable Cardioverter-defibrillator Registry. Eleventh Official Report
of the Spanish Society of Cardiology Electrophysiology and Arrhythmias Section
(2014).
AB - INTRODUCTION AND OBJECTIVES: We present the results of the Spanish Implantable
Cardioverter-defibrillator Registry for 2014, as compiled by the
Electrophysiology and Arrhythmia Section of the Spanish Society of Cardiology.
METHODS: Data collection sheets were voluntarily completed by each implantation
team and prospectively sent to the Spanish Society of Cardiology. RESULTS: The
number of reported implantations was 4911 (82% of the estimated total number of
implantations). The implantation rate was 106 per million population while the
estimated rate was 128. First implantations comprised 72.2%. Data were obtained
from 162 hospitals (8 more than in 2013). Most implantations (82%) were performed
in men. The mean patient age was 61.8+/-13.7 years. Most patients showed severe
or moderate-to-severe ventricular dysfunction and were in New York Heart
Association functional class II. The most frequent cardiac condition was ischemic
heart disease, followed by dilated cardiomyopathy. Implantations for primary
prevention indications comprised 58.5%. Electrophysiologists performed 85.6% of
the implantations. CONCLUSIONS: The 2014 Spanish Implantable Cardioverter
defibrillator Registry received information on 82% of the implantations performed
in Spain. The number of implantations has increased from previous years and the
percentage of implantations for primary prevention indications has increased from
the previous year.
PMID- 26443124
TI - Microscopic basis for the band engineering of Mo1-xWxS2-based heterojunction.
AB - Transition-metal dichalcogenide layered materials, consisting of a transition
metal atomic layer sandwiched by two chalcogen atomic layers, have been
attracting considerable attention because of their desirable physical properties
for semiconductor devices, and a wide variety of pn junctions, which are
essential building blocks for electronic and optoelectronic devices, have been
realized using these atomically thin structures. Engineering the
electronic/optical properties of semiconductors by using such heterojunctions has
been a central concept in semiconductor science and technology. Here, we report
the first scanning tunneling microscopy/spectroscopy (STM/STS) study on the
electronic structures of a monolayer WS2/Mo1-xWxS2 heterojunction that provides a
tunable band alignment. The atomically modulated spatial variation in such
electronic structures, i.e., a microscopic basis for the band structure of a
WS2/Mo1-xWxS2 heterojunction, was directly observed. The macroscopic band
structure of Mo1-xWxS2 alloy was well reproduced by the STS spectra averaged over
the surface. An electric field of as high as 80 * 10(6) Vm(-1) was observed at
the interface for the alloy with x = 0.3, verifying the efficient separation of
photoexcited carriers at the interface.
PMID- 26443125
TI - Hyperkalaemia in heart failure: binding the patient to improved treatment?
PMID- 26443123
TI - Stem and Progenitor Cell-Derived Astroglia Therapies for Neurological Diseases.
AB - Astroglia are a major cellular constituent of the central nervous system (CNS)
and play crucial roles in brain development, function, and integrity. Increasing
evidence demonstrates that astroglia dysfunction occurs in a variety of
neurological disorders ranging from CNS injuries to genetic diseases and chronic
degenerative conditions. These new insights herald the concept that
transplantation of astroglia could be of therapeutic value in treating the
injured or diseased CNS. Recent technological advances in the generation of human
astroglia from stem and progenitor cells have been prominent. We propose that a
better understanding of the suitability of astroglial cells in transplantation as
well as of their therapeutic effects in animal models may lead to the
establishment of astroglia-based therapies to treat neurological diseases.
PMID- 26443126
TI - Recombinant Mal d 1 facilitates sublingual challenge tests of birch pollen
allergic patients with apple allergy.
AB - It is still unclear whether allergen-specific immunotherapy (AIT) with birch
pollen improves birch pollen-related food allergy. One reason for this may be the
lack of standardized tests to assess clinical reactions to birch pollen-related
foods, for example apple. We tested the applicability of recombinant (r) Mal d 1,
the Bet v 1-homolog in apple, for oral challenge tests. Increasing concentrations
of rMal d 1 in 0.9% NaCl were sublingually administered to 72 birch pollen
allergic patients with apple allergy. The dose of 1.6 MUg induced oral allergy
syndromes in 26.4%, 3.2 MUg in 15.3%, 6.3 MUg in 27.8%, 12.5 MUg in 8.3%, 25 MUg
in 11.1%, and 50 MUg in 4.2% of the patients. No severe reactions occurred. None
of the patients reacted to 0.9% NaCl alone. Sublingual administration of 50 MUg
of rMal d 1 induced no reactions in three nonallergic individuals. Our approach
allows straight forward, dose-defined sublingual challenge tests in a high number
of birch pollen-allergic patients that inter alia can be applied to evaluate the
therapeutic efficacy of birch pollen AIT on birch pollen-related food allergy.
PMID- 26443127
TI - Towards understanding resprouting at the global scale.
AB - Understanding and predicting plant response to disturbance is of paramount
importance in our changing world. Resprouting ability is often considered a
simple qualitative trait and used in many ecological studies. Our aim is to show
some of the complexities of resprouting while highlighting cautions that need be
taken in using resprouting ability to predict vegetation responses across
disturbance types and biomes. There are marked differences in resprouting
depending on the disturbance type, and fire is often the most severe disturbance
because it includes both defoliation and lethal temperatures. In the
Mediterranean biome, there are differences in functional strategies to cope with
water deficit between resprouters (dehydration avoiders) and nonresprouters
(dehydration tolerators); however, there is little research to unambiguously
extrapolate these results to other biomes. Furthermore, predictions of vegetation
responses to changes in disturbance regimes require consideration not only of
resprouting, but also other relevant traits (e.g. seeding, bark thickness) and
the different correlations among traits observed in different biomes; models
lacking these details would behave poorly at the global scale. Overall, the
lessons learned from a given disturbance regime and biome (e.g. crown-fire
Mediterranean ecosystems) can guide research in other ecosystems but should not
be extrapolated at the global scale.
PMID- 26443128
TI - Electrostatic interactions in charged nanoslits within an explicit solvent
theory.
AB - Within a dipolar Poisson-Boltzmann theory including electrostatic correlations,
we consider the effect of explicit solvent structure on solvent and ion partition
confined to charged nanopores. We develop a relaxation scheme for the solution of
this highly non-linear integro-differential equation for the electrostatic
potential. The scheme is an extension of the approach previously introduced for
simple planes (Buyukdagli and Blossey 2014 J. Chem. Phys. 140 234903) to nanoslit
geometry. We show that the reduced dielectric response of solvent molecules at
the membrane walls gives rise to an electric field significantly stronger than
the field of the classical Poisson-Boltzmann equation. This peculiarity
associated with non-local electrostatic interactions results in turn in an
interfacial counterion adsorption layer absent in continuum theories. The
observation of this enhanced counterion affinity in the very close vicinity of
the interface may have important impacts on nanofluidic transport through charged
nanopores. Our results indicate the quantitative inaccuracy of solvent implicit
nanofiltration theories in predicting the ionic selectivity of membrane
nanopores.
PMID- 26443129
TI - Serum concentrations of cholesterol, apolipoprotein A-I and apolipoprotein B in a
total of 1694 meat-eaters, fish-eaters, vegetarians and vegans.
PMID- 26443131
TI - Revalidation rules must be clear from the start.
PMID- 26443130
TI - The use of personal flotation devices in the Northeast lobster fishing industry:
An examination of the decision-making process.
AB - BACKGROUND: This study explored perspectives of Northeast commercial lobstermen
regarding the use of personal flotation devices (PFDs). Researchers sought to
identify factors contributing to low PFD use, and motivators that could lead to
increased use of PFDs. METHODS: This qualitative research (n = 72) included 25
commercial fishermen who participated in in-depth, semi-structured interviews,
and 47 attendees of Lobstermen's meetings who engaged in focus groups. RESULTS:
The results showed substantial barriers to PFD use. Fishermen described
themselves as being proactive about safety whenever possible, but described a
longstanding tradition of not wearing PFDs. Key factors integrally linked with
the lack of PFD use were workability, identity/social stigma, and risk diffusion.
CONCLUSION: Future safety interventions will need to address significant barriers
to PFD use that include issues of comfort and ease of use, as well as social
acceptability of PFDs and reorientation of risk perceptions related to falls
overboard.
PMID- 26443132
TI - One in four nurses say stress and workload are driving them away.
PMID- 26443133
TI - Rugby World Cup bar gets people talking.
PMID- 26443134
TI - Call for nursing to be added to shortage occupation list.
PMID- 26443135
TI - NHS England to transform care for people with learning disabilities.
PMID- 26443136
TI - Band 5 and 6 nurses unaware of revalidation.
PMID- 26443137
TI - Pride award for Ebola survivors.
PMID- 26443138
TI - Stella creasy speaks out on 'crippling' PFIs.
PMID- 26443139
TI - QNI launches leadership plan for community nursing.
PMID- 26443141
TI - Staff get behind a good night's sleep.
PMID- 26443142
TI - NHS 111 could be 'overwhelmed' this winter without more nurses.
PMID- 26443143
TI - The ward feedback wall that is 'better than chocolates'.
PMID- 26443144
TI - Co-operation replaces competition as NHS shares best practice.
PMID- 26443150
TI - Foot health and homelessness.
PMID- 26443151
TI - Big lessons in revalidation.
AB - A huge revalidation pilot at Aneurin Bevan Health Board in Wales - more than 800
staff embarked on the process in February - has delivered important lessons for
other organisations and individual registrants about what to expect when they
begin the process.
PMID- 26443152
TI - Seeing cancer from a cultural perspective.
AB - Black and minority ethnic people are at risk of delayed cancer diagnoses because
of language barriers and the social stigma attached to cancer in some
communities. Nurses can help by acting as advocates for patients, and by being
aware of the risks for different ethnic groups.
PMID- 26443165
TI - As nurses we should understand the dilemma over RAF sergeant.
PMID- 26443166
TI - Let's communicate better with children who have complex needs.
PMID- 26443167
TI - NHS interview panels must do more to encourage would-be BME leaders.
PMID- 26443168
TI - No one should miss out on end of life care offered by Marie Curie.
PMID- 26443169
TI - How does Jeremy Hunt propose I spend more time with patients?
PMID- 26443170
TI - What you're saying on our Facebook page....
PMID- 26443172
TI - Correction.
PMID- 26443174
TI - How to remove a chest drain.
AB - RATIONALE AND KEY POINTS: This article aims to help nurses to undertake the
removal of a chest drain in a safe, effective and patient-centred manner. This
procedure requires two practitioners. The chest drain will have been inserted
aseptically to remove air, blood, fluid or pus from the pleural cavity. ? Chest
drains may be small or wide bore depending on the underlying condition and
clinical setting. They may be secured with a mattress suture and/or an anchor
suture. ? Chest drains are usually removed under medical instructions when the
patient's lung has inflated, the underlying condition has resolved, there is no
evidence of respiratory compromise or failure, and their anticoagulation status
has been assessed as satisfactory. ? Chest drains secured with a mattress suture
should be removed by two practitioners. One practitioner is required to remove
the tube and the other to tie the mattress suture (if present) and secure the
site. REFLECTIVE ACTIVITY: Clinical skills articles can help update your practice
and ensure it remains evidence based. Apply this article to your practice.
Reflect on and write a short account of: 1. How reading this article will change
your practice. 2. How this article could be used to educate patients with chest
drains. Subscribers can upload their reflective accounts at: rcni.com/portfolio .
PMID- 26443175
TI - Improving diabetes care at the end of life.
AB - The number of people with diabetes in the UK is increasing. Many are aged over 75
years, and this has resulted in rising numbers of patients for whom diabetes
exists comorbidly with other disease processes. Those with life-limiting illness
require palliative care services. However, end of life care for patients with
diabetes is generally poor. The aim of end of life care for these individuals is
to maintain comfort, while minimising the risks of osmotic symptoms. The wishes
of patients, carers and families should be taken into consideration when agreeing
new glucose control targets, adjusting treatment or changing focus on diet.
Patients and carers should feel that the condition is being managed with the
support of healthcare professionals. These professionals need the knowledge,
skills and confidence to recognise the end of life to tailor diabetes care
appropriately.
PMID- 26443176
TI - Supporting band 5 practitioners in professional and leadership roles.
AB - Interest in professionalism and leadership has increased within the nursing and
midwifery community. The NHS Lanarkshire Practice Development Centre established
a study day on these concepts for band 5 practitioners. This formed part of NHS
Lanarkshire's implementation of Scotland's nursing and midwifery leadership
development strategy, Leading Better Care. The aims of the study day were to
reinforce individual professional responsibility, promote the principles of
professionalism and explore the concept of leadership in the band 5 role. This
article reports on the development, implementation and evaluation of the study
day.
PMID- 26443177
TI - Caring for patients with limb amputation.
AB - This article provides an overview of the care of patients undergoing limb
amputation. Absence of a limb can be congenital or the result of trauma or
complications of chronic diseases. While the economic burden of limb amputation
is significant, nurses have an important role in limiting other losses
attributable to limb loss, such as long-term disability leading to loss of
employment and delayed return to work or school. Comprehensive nursing
assessments and appropriate interventions, pre and post-operatively, as well as
early discharge planning and community reintegration can help avoid some of these
losses. Nurses should be aware of the resources available in communities and work
in multidisciplinary teams to ensure optimal outcomes for patients following limb
amputation and their families.
PMID- 26443178
TI - Intramuscular injection.
PMID- 26443179
TI - Prepare to succeed.
PMID- 26443181
TI - Values light the way to work.
PMID- 26443182
TI - Succeed as an agency nurse.
PMID- 26443183
TI - Student life - encouraging students to opt for mental health.
PMID- 26443184
TI - Mutation Update for COL2A1 Gene Variants Associated with Type II
Collagenopathies.
AB - Mutations in the COL2A1 gene cause a spectrum of rare autosomal-dominant
conditions characterized by skeletal dysplasia, short stature, and sensorial
defects. An early diagnosis is critical to providing relevant patient care and
follow-up, and genetic counseling to affected families. There are no recent
exhaustive descriptions of the causal mutations in the literature. Here, we
provide a review of COL2A1 mutations extracted from the Leiden Open Variation
Database (LOVD) that we updated with data from PubMed and our own patients. Over
700 patients were recorded, harboring 415 different mutations. One-third of the
mutations are dominant-negative mutations that affect the glycine residue in the
G-X-Y repeats of the alpha 1 chain. These mutations disrupt the collagen triple
helix and are common in achondrogenesis type II and hypochondrogenesis. The
mutations resulting in a premature stop codon are found in less severe phenotypes
such as Stickler syndrome. The p.(Arg275Cys) substitution is found in all
patients with COL2A1-associated Czech dysplasia. LOVD-COL2A1 provides support and
potential collaborative material for scientific and clinical projects aimed at
elucidating phenotype-genotype correlation and differential diagnosis in patients
with type II collagenopathies.
PMID- 26443185
TI - Exfoliation of large-area transition metal chalcogenide single layers.
AB - Isolating large-areas of atomically thin transition metal chalcogenide crystals
is an important but challenging task. The mechanical exfoliation technique can
provide single layers of the highest structural quality, enabling to study their
pristine properties and ultimate device performance. However, a major drawback of
the technique is the low yield and small (typically < 10 MUm) lateral size of the
produced single layers. Here, we report a novel mechanical exfoliation technique,
based on chemically enhanced adhesion, yielding MoS2 single layers with typical
lateral sizes of several hundreds of microns. The idea is to exploit the chemical
affinity of the sulfur atoms that can bind more strongly to a gold surface than
the neighboring layers of the bulk MoS2 crystal. Moreover, we found that our
exfoliation process is not specific to MoS2, but can be generally applied for
various layered chalcogenides including selenites and tellurides, providing an
easy access to large-area 2D crystals for the whole class of layered transition
metal chalcogenides.
PMID- 26443187
TI - Smokeless tobacco-associated cancers: A systematic review and meta-analysis of
Indian studies.
AB - The International Agency for Research on Cancer (IARC) has concluded that there
is sufficient evidence in humans for the carcinogenicity of smokeless tobacco
(SLT) for mouth, oesophagus and pancreas, based largely on Western studies. We
wanted to confirm this by conducting a systematic review using Indian studies
because India faces the biggest brunt of SLT-attributable health effects. A
systematic search was conducted for published and unpublished studies. Two
authors independently reviewed the studies and extracted data. Summary odds ratio
(OR) for each cancer type was calculated using fixed and random effects model.
The population attributable fraction (PAF) method was used to calculate the
attributable burden of incident cases. A significant association was found for
oral-5.55 (5.07, 6.07), pharyngeal-2.69 (2.28, 3.17), laryngeal-2.84 (2.18,
3.70), oesophageal-3.17 (2.76, 3.63) and stomach-1.26 (1.00, 1.60) cancers. But
in random effects model, laryngeal-1.79 (0.70, 4.54) and stomach-1.31 (0.92,
1.87) cancers became non-significantly associated. Gender-wise analysis revealed
that women had a higher risk (OR = 12.0 vs. 5.16) of oral but a lower risk (1.9
vs. 4.5) of oesophageal cancer compared with men. For oral cancer, studies that
adjusted for smoking, alcohol and other factors reported a significantly lower OR
compared with studies that adjusted for smoking only or smoking and alcohol only
(3.9 vs. 8.4). The annual number of attributable cases was calculated as 49,192
(PAF = 60%) for mouth, 14,747 (51%) for pharynx, 11,825 (40%) for larynx, 14,780
(35%) for oesophagus and 3,101 (8%) for stomach.
PMID- 26443188
TI - A proposal for a preoperative clinical scoring system for acute cholecystitis.
AB - BACKGROUND: Acute cholecystitis is a common diagnosis for which surgery is
usually indicated. However, the heterogeneity of clinical presentation makes it
difficult to standardize management. The variation in clinical presentation is
influenced by both patient-dependent and disease-specific factors. A preoperative
clinical scoring system designed to included patient-dependent and clinical
factors might be a useful tool in clinical decision making. METHODS: The data of
patients undergoing laparoscopic cholecystectomy for acute cholecystitis in a
university hospital were retrospectively reviewed. Patient-dependent factors
(age, sex, body mass index, and American Society of Anesthesiologists score) and
disease-specific factors (history of biliary colics, white blood count, C
reactive protein, and gallbladder wall thickness) were used to compute a clinical
score between zero and nine for each patient. Cholecystitis was classified as
mild (score <= 3), moderate (4 <= score <= 6), or severe (score >= 7). RESULTS:
Cholecystitis was mild in 45 cases, moderate in 105 cases, and severe in 27
cases. Among patient-dependent factors, the male gender, age >65 y, and American
Society of Anesthesiologists score >2 correlated significantly with high scores,
P = 0.001. Equally, high white blood count, elevated C-reactive protein, and
gallbladder wall thickness >4 mm correlated significantly with high scores, P =
0.001. These findings were confirmed on multivariate analyses. High scores
correlated significantly with the duration of surgery (P = 0.007), the need of
intensive care unit management (P = 0.001) and the length of stay (P = 0.001).
However, there was no significant association between the preoperative score and
the rate of conversion (P = 0.103) or the rate of complication (P = 0.209).
CONCLUSIONS: This preoperative clinical scoring system has a potential to select
patients with severe cholecystitis and therefore might be a useful tool in
clinical decision making.
PMID- 26443186
TI - Vinorelbine and epirubicin share common features with polysialic acid and
modulate neuronal and glial functions.
AB - Polysialic acid (PSA), a large, linear glycan composed of 8 to over 100 alpha2,8
linked sialic acid residues, modulates development of the nervous system by
enhancing cell migration, axon pathfinding, and synaptic targeting and by
regulating differentiation of progenitor cells. PSA also functions in developing
and adult immune systems and is a signature of many cancers. In this study we
identified vinorelbine, a semi-synthetic third generation vinca alkaloid, and
epirubicin, an anthracycline and 4'-epimer of doxorubicin, as PSA mimetics.
Similar to PSA, vinorelbine and epirubicin bind to the PSA-specific monoclonal
antibody 735 and compete with the bacterial analog of PSA, colominic acid in
binding to monoclonal antibody 735. Vinorelbine and epirubicin stimulate neurite
outgrowth of cerebellar neurons via the neural cell adhesion molecule, via
myristoylated alanine-rich C kinase substrate, and via fibroblast growth factor
receptor, signaling through Erk pathways. Furthermore, the two compounds enhance
process formation of Schwann cells and migration of cerebellar neurons in
culture, and reduce migration of astrocytes after injury. These novel results
show that the structure and function of PSA can be mimicked by the small organic
compounds vinorelbine and epirubicin, thus raising the possibility to re-target
drugs used in treatment of cancers to nervous system repair. Vinorelbine and
epirubicin, identified as PSA mimetics, enhance, like PSA, neuronal migration,
neuritogenesis, and formation of Schwann cell processes, and reduce astrocytic
migration. Ablating NCAM, inhibiting fibroblast growth factor (FGFR) receptor, or
adding the effector domain of myristoylated alanine-rich C kinase substrate
(MARCKS) minimize the vinorelbine and epirubicin effects, indicating that they
are true PSA mimetics triggering PSA-mediated functions.
PMID- 26443189
TI - Normal mast cell numbers in the tissues of AhR-deficient mice.
AB - The transcription factor aryl hydrocarbon receptor (AhR) acts as an
immunomodulatory molecule in several immune cell lineages. Recently, it has been
implicated in development and maintenance of immune cells in barrier tissues such
as skin and mucosa. To investigate its role on mast cell development and
maintenance in skin, peritoneal exudate cells (PECs) and lymph nodes, we studied
in depth their phenotype in AhR-deficient mice. Our findings do not provide any
evidence for a suspected role of the AhR in mast cell homeostasis.
PMID- 26443190
TI - Translating the genome in time and space: specialized ribosomes, RNA regulons,
and RNA-binding proteins.
AB - A central question in cell and developmental biology is how the information
encoded in the genome is differentially interpreted to generate a diverse array
of cell types. A growing body of research on posttranscriptional gene regulation
is revealing that both global protein synthesis rates and the translation of
specific mRNAs are highly specialized in different cell types. How this exquisite
translational regulation is achieved is the focus of this review. Two levels of
regulation are discussed: the translation machinery and cis-acting elements
within mRNAs. Recent evidence shows that the ribosome itself directs how the
genome is translated in time and space and reveals surprising functional
specificity in individual components of the core translation machinery. We are
also just beginning to appreciate the rich regulatory information embedded in the
untranslated regions of mRNAs, which direct the selective translation of
transcripts. These hidden RNA regulons may interface with a myriad of RNA-binding
proteins and specialized translation machinery to provide an additional layer of
regulation to how transcripts are spatiotemporally expressed. Understanding this
largely unexplored world of translational codes hardwired in the core translation
machinery is an exciting new research frontier fundamental to our understanding
of gene regulation, organismal development, and evolution.
PMID- 26443191
TI - Placenta: the forgotten organ.
AB - The placenta sits at the interface between the maternal and fetal vascular beds
where it mediates nutrient and waste exchange to enable in utero existence.
Placental cells (trophoblasts) accomplish this via invading and remodeling the
uterine vasculature. Amazingly, despite being of fetal origin, trophoblasts do
not trigger a significant maternal immune response. Additionally, they maintain a
highly reliable hemostasis in this extremely vascular interface. Decades of
research into how the placenta differentiates itself from embryonic tissues to
accomplish these and other feats have revealed a previously unappreciated level
of complexity with respect to the placenta's cellular composition. Additionally,
novel insights with respect to roles played by the placenta in guiding fetal
development and metabolism have sparked a renewed interest in understanding the
interrelationship between fetal and placental well-being. Here, we present an
overview of emerging research in placental biology that highlights these themes
and the importance of the placenta to fetal and adult health.
PMID- 26443192
TI - Motors, anchors, and connectors: orchestrators of organelle inheritance.
AB - Organelle inheritance is a process whereby organelles are actively distributed
between dividing cells at cytokinesis. Much valuable insight into the molecular
mechanisms of organelle inheritance has come from the analysis of asymmetrically
dividing cells, which transport a portion of their organelles to the bud while
retaining another portion in the mother cell. Common principles apply to the
inheritance of all organelles, although individual organelles use specific
factors for their partitioning. Inheritance factors can be classified as motors,
which are required for organelle transport; anchors, which immobilize organelles
at distinct cell structures; or connectors, which mediate the attachment of
organelles to motors and anchors. Here, we provide an overview of recent advances
in the field of organelle inheritance and highlight how motor, anchor, and
connector molecules choreograph the segregation of a multicopy organelle, the
peroxisome. We also discuss the role of organelle population control in the
generation of cellular diversity.
PMID- 26443193
TI - Systematic review: factors contributing to burnout in dentistry.
AB - BACKGROUND: Dentists and dental students have been reported to be at high risk of
burnout and risk factors have been identified. Despite research into burnout in
dentists, only a few papers have identified significantly associated factors.
AIMS: To identify the most significant factors associated with burnout in
dentists and dental students in published literature. METHODS: We systematically
searched MEDLINE, EMBASE and HMIC electronic databases to source literature on
the factors associated with burnout in dentists. We critically appraised and
themed papers using the Critical Appraisal Skills Programme to find the most
significant factors. RESULTS: From 115 studies identified by the search string,
we deemed 33 papers to be relevant for review. The most prevalent and significant
factors associated with burnout were: younger age, male gender, student status,
high job-strain/working hours, those enrolled in clinical degree programmes and
certain personality types. However, only a limited amount of literature explored
the directional relationship between these factors and burnout. CONCLUSIONS: This
review identified several significant factors contributing to burnout in dentists
and dental students. Further longitudinal and prospective studies are required to
assess causation. Burnout should be considered a multifactorial phenomenon that
can develop early in a dental career. Screening programmes and coping strategies
might help to identify and prevent it.
PMID- 26443195
TI - Heptagons in Aromatics: From Monocyclic to Polycyclic.
PMID- 26443194
TI - Can Chinese Herbal Medicine Adjunctive Therapy Improve Outcomes of Senile
Vascular Dementia? Systematic Review with Meta-analysis of Clinical Trials.
AB - Many publications have reported the growing application of complementary and
alternative medicine, particularly the use of Chinese herbal medicine (CHM) in
combination with routine pharmacotherapy (RP) for senile vascular dementia (SVD),
but its efficacy remains largely unexplored. The purpose of this study is to
evaluate the efficacy of CHM adjunctive therapy (CHMAT), which is CHM combined
with RP, in the treatment of SVD. Publications in seven electronic databases were
searched extensively, and 27 trials with a total of 1961 patients were included
for analysis. Compared with RP alone, CHMAT significantly increased the effective
rate [odds ratio (OR) 2.98, 95% confidence interval (CI) 2.30, 3.86]. In
addition, CHMAT showed benefits in detailed subgroups of the Mini-Mental State
Exam (MMSE) score from time of onset to 4 weeks (WMD 3.01, 95% CI 2.15, 3.87), 8
weeks (weighted mean difference (WMD) 2.30, 95% CI 1.28, 3.32), 12 weeks (WMD
2.93, 95% CI 2.17, 3.69), and 24 weeks (WMD 3.25, 95% CI 2.61, 3.88), and in the
activity of daily living scale score from time of onset to 4 weeks (WMD -4.64,
95% CI -6.12, -3.17), 8 weeks (WMD -4.30, 95% CI -6.04, -2.56), 12 weeks (WMD
3.89, 95% CI -4.68, -3.09), and 24 weeks (WMD -4.04, 95% CI -6.51, -1.57).
Moreover, CHMAT had positive effects on changes in the Hasegawa dementia scale,
National Institutes of Health Stroke Scale, Clinical Dementia Rating, and
Montreal Cognitive Assessment scores, as well as blood fat levels (total
cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density
lipoprotein cholesterol, and apolipoprotein E), platelet aggregation rate (1-min
platelet aggregation rate, 5-min platelet aggregation rate, and maximal platelet
aggregation rate), and blood rheology (whole-blood viscosity and hematocrit). No
serious or frequently occurring adverse effects were reported. Weaknesses of
methodological quality in most trials were assessed using the Cochrane risk of
bias tool, while the quality level of Grades of Recommendations Assessment
Development and Evaluation (GRADE) evidence classification indicated 'very low'.
This systematic review suggests that CHM as an adjunctive therapy can improve
cognitive impairment and enhance immediate response and quality of life in SVD
patients. However, because of limitations of methodological quality in the
included studies, further research of rigorous design is needed.
PMID- 26443196
TI - Comparison of antiplatelet effect and safety of clopidogrel napadisilate with
clopidogrel bisulfate in stroke patients: multicenter, randomized, open-label,
phase 4, non-inferiority clinical trial.
AB - OBJECTIVE: Clopidogrel napadisilate has better chemical stability than
clopidogrel bisulfate. Our trial's objective was to compare the efficacy and
safety of clopidogrel napadisilate with clopidogrel bisulfate in participants
with ischemic stroke. RESEARCH DESIGN AND METHODS: The study was a phase 4, 4
week, randomized, parallel-group, non-inferiority trial. Patients with ischemic
stroke were randomized to receive either clopidogrel napadisilate 75 mg or
clopidogrel bisulfate 75 mg. The primary study endpoint was change from baseline
in P2Y12 percentage inhibition at week 4. The primary analysis was conducted in
the per-protocol population. Non-inferiority was confirmed if the lower limit of
the 95% confidence interval (CI) of the treatment difference was greater than or
equal to -9.0% points. RESULTS: Sixty-one participants were randomly assigned
clopidogrel napadisilate and 60 were randomly assigned clopidogrel bisulfate.
Thirty-nine participants in the clopidogrel napadisilate group and 39 in the
clopidogrel bisulfate group were analyzed for the primary endpoint. At 4 weeks,
mean P2Y12 percentage inhibition had increased in both treatment groups. The
estimated mean change from baseline was 22.3% with clopidogrel napadisilate and
21.4% with clopidogrel bisulfate; the estimated treatment difference of 0.9% (95%
CI, -8.6 to 10.4) confirmed the non-inferiority of clopidogrel napadisilate to
clopidogrel bisulfate. CONCLUSIONS: Clopidogrel napadisilate was non-inferior to
clopidogrel bisulfate as assessed by change in P2Y12 percentage inhibition. Rates
of adverse events were similar between the two groups. Therefore, clopidogrel
napadisilate is a useful alternative option for the dosing of ischemic stroke
patient populations.
PMID- 26443197
TI - Glycation of human serum albumin alters its binding efficacy towards the dietary
polyphenols: a comparative approach.
AB - Diabetes is a major problem in the world. The proteins became modified during
glycation after reacting with the reducing sugars (e.g. D-glucose) via non
enzymatic pathways. The glycated analogue of human serum albumin (HSA) has been
characterized with the help of multi-spectroscopic methods. It has been observed
that six glucose molecules can bind covalently to HSA under experimental
condition. The binding affinity of the modified HSA towards the dietary
polyphenols has been estimated using UV-vis and fluorescence spectroscopic
techniques. The binding constant values of the ligands were found to decrease
after the modification of HSA.
PMID- 26443198
TI - Posttranslational modification of E-cadherin by core fucosylation regulates Src
activation and induces epithelial-mesenchymal transition-like process in lung
cancer cells.
AB - E-cadherin is often dysregulated in aggressive lung cancer, the mechanism of
which cannot always be explained at the level of transcription. In 66 patients
with lung cancer, immunohistochemical staining demonstrated that co-localization
of E-cadherin and core fucose by Lens culinaris agglutinin was significantly less
extensive in tumor than in nontumor tissue. Through gain and loss of fucosylation
experiments in the giant lung carcinoma cell lines 95C and 95D, our results
revealed that E-cadherin core fucosylation in 95C cells overexpressing alpha-1, 6
fucosyltransferase (Fut8) inhibited Fut8-95C cell migration, whereas knockdown of
Fut8 in 95D cells enhanced migration of short-interfering RNA-targeting Fut8
(siFut8)-95D cells. The level of active Src (phosphorylated Src [Y416]) was
significantly reduced in Fut8-95C cells, but elevated in siFut8-95D cells. In
protein complexes immunoprecipitated from Fut8-95C cell lysates with anti-E
cadherin, less phosphorylated Src (Y416) and more beta-catenin were observed, but
immunoprecipitates from siFut8-95D cells, containing less core fucosylated E
cadherin, contained an elevated level of phospho-Src Y416. In Fut8-95C cells,
phosphorylation of Akt (Y315, Y326) and GSK-3beta (S9) was significantly reduced,
but beta-catenin (S37) phosphorylation was enhanced. Expression of N-cadherin and
Snail1 was also reduced in Fut8-95C cells, but significantly increased in siFut8
95D cells. Intriguingly, when Src kinase activity was inhibited by treatment of
cells with PP2 and SU6656, regulation of N-cadherin, Snail1 and cell migration by
E-cadherin core fucosylation was abrogated in both Fut8-95C and siFut8-95D cells.
Therefore, posttranslational modification of E-cadherin by less core fucosylation
recruited and activated Src, and induced an epithelial-mesenchymal transition
like process in lung cancer cells.
PMID- 26443199
TI - Aurantivirga profunda gen. nov., sp. nov., isolated from deep-seawater, a novel
member of the family Flavobacteriaceae.
AB - A Gram-stain-negative, aerobic, proteorhodopsin-containing, orange, rod-shaped
bacterium, designated SAORIC-234T, was isolated from deep seawater in the Pacific
Ocean. 16S rRNA gene sequence analysis revealed that the strain could be
affiliated with the family Flavobacteriaceae of the phylum Bacteroidetes and
shared less than 94.6 % similarity with other species of the family with validly
published names. The phenotypic characteristics of this novel isolate, such as
growth properties and enzyme activities, could be differentiated from those of
other species. The strain was non-motile, oxidase-positive and catalase-negative.
The G+C content of the genomic DNA was determined to be 34.8 mol% and menaquinone
6 (MK-6) was the predominant isoprenoid quinone. The predominant fatty acids were
iso-C15 : 0, iso-C15 : 1 G, iso-C16 : 0 3-OH, iso-C17 : 0 3-OH and iso-C15 : 0 3
OH. The major polar lipids comprised phosphatidylethanolamine, three unknown
aminolipids and three unknown lipids. On the basis of the taxonomic data
collected in this study, it was concluded that strain SAORIC-234T represents a
novel genus and species in the family Flavobacteriaceae, for which the name
Aurantivirga profunda gen. nov., sp. nov. is proposed. The type strain of the
type species, Aurantivirga profunda sp. nov., is SAORIC-234T ( = NBRC 110606T =
KACC 18400T).
PMID- 26443200
TI - C-H activation in Ir(III) and N-demethylation in Pt(II) complexes with mesoionic
carbene ligands: examples of monometallic, homobimetallic and heterobimetallic
complexes.
AB - Mononuclear Pt(II) and the first dinuclear Pt(II) complexes along with a
cyclometalated heterobimetallic Ir(III)/Pd(II) complex bearing mesoionic carbene
donor ligands are presented starting from the same bis-triazolium salt. The
mononuclear Pt(II) complex possesses a free triazole moiety which is generated
from the corresponding triazolium salt through an N-demethylation reaction,
whereas the mononuclear Ir(III) complex features an unreacted triazolium unit.
PMID- 26443202
TI - Prenatal vesico-allantoic cyst outcome - a spectrum from patent urachus to
bladder exstrophy.
AB - OBJECTIVE: The purpose of this study is to assess the prognostic significance of
a cystic vesico-allantoic communication discovered on prenatal ultrasound in
terms of its effect on the developing urinary tract. METHODS: Multi-institution
review of prenatal screening ultrasound was performed between 2004 and 2015 to
identify cases of in utero communication between the fetal urinary bladder and a
cystic dilatation of the umbilical cord. Gestational age at diagnosis, perinatal
evolution, and eventual urinary tract outcome are described and compared with
existing literature. RESULTS: Five cases of cystic vesico-allantoic communication
were identified on second-trimester screening ultrasound. Serial ultrasounds
showed an increase in the size of the umbilical cystic component with gestational
age, followed by its eventual rupture prior to delivery. All neonates had urinary
leakage through the inferior portion of the umbilicus with bladder prolapse
ranging from patent urachus to partial bladder exstrophy. CONCLUSIONS: An
isolated prenatal ultrasound finding of an hourglass communication between the
fetal bladder and a cyst of the umbilical cord should be considered predictive of
a spectrum from patent urachus to bladder exstrophy. Given the significant
ramications on the developing urinary tract, the prenatal finding of vesico
allantoic cyst warrants referral to a high-risk obstetrical center with urologic
consultation.
PMID- 26443201
TI - Epigenetic silencing of the XAF1 gene is mediated by the loss of CTCF binding.
AB - XAF1 is a tumour suppressor gene that compromises cell viability by modulating
different cellular events such as mitosis, cell cycle progression and apoptosis.
In cancer, the XAF1 gene is commonly silenced by CpG-dinucleotide
hypermethylation of its promoter. DNA demethylating agents induce transcriptional
reactivation of XAF1, sensitizing cancer cells to therapy. The molecular
mechanisms that mediate promoter CpG methylation have not been previously
studied. Here, we demonstrate that CTCF interacts with the XAF1 promoter in vivo
in a methylation-sensitive manner. By transgene assays, we demonstrate that CTCF
mediates the open-chromatin configuration of the XAF1 promoter, inhibiting both
CpG-dinucleotide methylation and repressive histone posttranslational
modifications. In addition, the absence of CTCF in the XAF1 promoter inhibits
transcriptional activation induced by well-known apoptosis activators. We report
for the first time that epigenetic silencing of the XAF1 gene is a consequence of
the loss of CTCF binding.
PMID- 26443203
TI - [New physical therapy procedures].
PMID- 26443206
TI - Nanoscale Graphene Disk: A Natural Functionally Graded Material-How is Fourier's
Law Violated along Radius Direction of 2D Disk.
AB - In this Paper, we investigate numerically and analytically the thermal
conductivity of nanoscale graphene disks (NGDs), and discussed the possibility to
realize functionally graded material (FGM) with only one material, NGDs.
Different from previous studies on divergence/non-diffusive of thermal
conductivity in nano-structures with different size, we found a novel non
homogeneous (graded) thermal conductivity along the radius direction in a single
nano-disk structure. We found that, instead of a constant value, the NGD has a
graded thermal conductivity along the radius direction. That is, Fourier's law of
heat conduction is not valid in two dimensional graphene disk structures
Moreover, we show the dependent of NGDs' thermal conductivity on radius and
temperature. Our study might inspire experimentalists to develop NGD based
versatile FGMs, improve understanding of the heat removal of hot spots on chips,
and enhance thermoelectric energy conversion efficiency by two dimensional disk
with a graded thermal conductivity.
PMID- 26443208
TI - Musculoskeletal complications of haematological disease.
AB - Rheumatological manifestations complicate many benign and malignant blood
disorders. Significant advances in haematology, with improved diagnostic
techniques and newer musculoskeletal imaging, have occurred in the past two
decades. This review focuses on the interrelationship between the major
haematological diseases (haemochromatosis, haemophilia, sickle cell disease,
thalassaemia, leukaemia, lymphoma, myelodysplastic syndromes, multiple myeloma
and cryoglobulinaemia) and rheumatic manifestations.
PMID- 26443209
TI - Xanthomonas and the TAL Effectors: Nature's Molecular Biologist.
AB - Agrobacterium, due to the transfer of T-DNA to the host genome, is known as
nature's genetic engineer. Once again, bacteria have led the way to newfound
riches in biotechnology. Xanthomonas has emerged as nature's molecular biologist
as the functional domains of the sequence-specific DNA transcription factors
known as TAL effectors were characterized and associated with the cognate disease
susceptibility and resistance genes of plants.
PMID- 26443207
TI - NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase
activity.
AB - The SMC5/6 complex is the least understood of SMC complexes. In yeast, smc5/6
mutants phenocopy mutations in sgs1, the BLM ortholog that is deficient in
Bloom's syndrome (BS). We here show that NSMCE2 (Mms21, in Saccharomyces
cerevisiae), an essential SUMO ligase of the SMC5/6 complex, suppresses cancer
and aging in mice. Surprisingly, a mutation that compromises NSMCE2-dependent
SUMOylation does not have a detectable impact on murine lifespan. In contrast,
NSMCE2 deletion in adult mice leads to pathologies resembling those found in
patients of BS. Moreover, and whereas NSMCE2 deletion does not have a detectable
impact on DNA replication, NSMCE2-deficient cells also present the cellular
hallmarks of BS such as increased recombination rates and an accumulation of
micronuclei. Despite the similarities, NSMCE2 and BLM foci do not colocalize and
concomitant deletion of Blm and Nsmce2 in B lymphocytes further increases
recombination rates and is synthetic lethal due to severe chromosome mis
segregation. Our work reveals that SUMO- and BLM-independent activities of NSMCE2
limit recombination and facilitate segregation; functions of the SMC5/6 complex
that are necessary to prevent cancer and aging in mice.
PMID- 26443210
TI - TAL Effector DNA-Binding Principles and Specificity.
AB - Transcription activator-like effectors (TALEs) are proteins with a unique DNA
binding domain that confers both a predictable and programmable specificity. The
DNA-binding domain consists typically of 34-amino acid near-identical repeats.
The repeats form a right-handed superhelical structure that wraps around the DNA
double helix and exposes the variable amino acids at position 13 of each repeat
to the sense strand DNA bases. Each repeat binds one base in a highly specific,
non-overlapping, and comma-free fashion. Although TALE specificities are encoded
in a simple way, sophisticated rules can be taken into account to build highly
efficient DNA-binding modules for biotechnological use.
PMID- 26443212
TI - Online Tools for TALEN Design.
AB - Transcription activator-like effector nucleases (TALENs) can be exquisitely
specific and highly effective genome editing reagents. Specificity and efficacy
depend however on good design for minimal off-targeting and strong binding.
Several online tools are accessible to aid in this process. Here, we tabulate
those tools, noting their functions and key features.
PMID- 26443213
TI - Assembly of Customized TAL Effectors Through Advanced ULtiMATE System.
AB - Transcription activator-like effectors (TALEs) have been widely applied in gene
targeting. Here we describe an advanced ULtiMATE (USER-based Ligation-Mediated
Assembly of TAL Effector) system that utilizes USER fusion technique and archive
of 512 tetramer templates to achieve highly efficient construction of TALEs,
which takes only half a day to accomplish the assembly of any given TALE
construct. This system is also suitable for large-scale assembly of TALENs and
any other TALE-based constructions.
PMID- 26443211
TI - The Development of TALE Nucleases for Biotechnology.
AB - The development of a facile genome engineering technology based on transcription
activator-like effector nucleases (TALENs) has led to significant advances in
diverse areas of science and medicine. In this review, we provide a broad
overview of the development of TALENs and the use of this technology in basic
science, biotechnology, and biomedical applications. This includes the discovery
of DNA recognition by TALEs, engineering new TALE proteins to diverse targets,
general advances in nuclease-based editing strategies, and challenges that are
specific to various applications of the TALEN technology. We review examples of
applying TALENs for studying gene function and regulation, generating disease
models, and developing gene therapies. The current status of genome editing and
future directions for other uses of these technologies are also discussed.
PMID- 26443214
TI - Engineering Customized TALENs Using the Platinum Gate TALEN Kit.
AB - Among various strategies for constructing customized transcription activator-like
effector nucleases (TALENs), the Golden Gate assembly is the most widely used and
most characterized method. The principle of Golden Gate assembly involves cycling
reactions of digestion and ligation of multiple plasmids in a single tube,
resulting in PCR-, fragmentation-, and purification-free concatemerization of DNA
binding repeats. Here, we describe the protocols for Golden Gate assembly-based
TALEN construction using the Platinum Gate TALEN Kit, which allows generation of
highly active Platinum TALENs.
PMID- 26443215
TI - Design, Assembly, and Characterization of TALE-Based Transcriptional Activators
and Repressors.
AB - Transcription activator-like effectors (TALEs) are modular DNA-binding proteins
that can be fused to a variety of effector domains to regulate the epigenome.
Nucleotide recognition by TALE monomers follows a simple cipher, making this a
powerful and versatile method to activate or repress gene expression. Described
here are methods to design, assemble, and test TALE transcription factors (TALE
TFs) for control of endogenous gene expression. In this protocol, TALE arrays are
constructed by Golden Gate cloning and tested for activity by transfection and
quantitative RT-PCR. These methods for engineering TALE-TFs are useful for
studies in reverse genetics and genomics, synthetic biology, and gene therapy.
PMID- 26443216
TI - A New Approach to Dissect Nuclear Organization: TALE-Mediated Genome
Visualization (TGV).
AB - Spatiotemporal organization of chromatin within the nucleus has so far remained
elusive. Live visualization of nuclear remodeling could be a promising approach
to understand its functional relevance in genome functions and mechanisms
regulating genome architecture. Recent technological advances in live imaging of
chromosomes begun to explore the biological roles of the movement of the
chromatin within the nucleus. Here I describe a new technique, called TALE
mediated genome visualization (TGV), which allows us to visualize endogenous
repetitive sequence including centromeric, pericentromeric, and telomeric repeats
in living cells.
PMID- 26443217
TI - TALEN-Induced Translocations in Human Cells.
AB - Induction of chromosomal translocations in human cells is of a great interest to
study tumorigenesis and genome instability. Here, we explain in detail a method
to induce translocations using the transcription activator-like effector
nucleases (TALENs). We describe how to detect translocation formation by PCR,
calculate translocation frequency by 96-well PCR screen, and analyze breakpoint
junctions. When inducing cancer translocations, it is also possible to detect the
fusion gene by FISH analysis or western blot.
PMID- 26443218
TI - Mutagenesis in Newts: Protocol for Iberian Ribbed Newts.
AB - Newts have the remarkable capability of organ/tissue regeneration, and have been
used as a unique experimental model for regenerative biology. The Iberian ribbed
newt (Pleurodeles waltl) is suitable as a model animal. We have established
methods for artificial insemination and efficient transgenesis using P. waltl
newts. In addition to the transgenic technique, development of TALENs enables
targeting mutagenesis in the newts. We have reported that TALENs efficiently
disrupted targeted genes in newt embryos. In this chapter, we introduce a
protocol for TALEN-mediated gene targeting in Iberian ribbed newts.
PMID- 26443219
TI - Targeted Mutagenesis in Bombyx mori Using TALENs.
AB - Bombyx mori is a valuable model organism of high economic importance. Its genome
sequence is available, as well as basic genetic and molecular genetic tools and
markers. The introduction of genome editing methods based on engineered nucleases
enables precise manipulations with genomic DNA, including targeted DNA deletions,
insertions, or replacements in the genome allowing gene analysis and various
applications. We describe here the use of TALENs which have a simple modular
design of their DNA-binding domains, are easy to prepare and proved to be
efficient in targeting of a wide range of cleavage sites. Our procedure often
allows the production of individuals carrying homozygous mutations as early as in
the G1 generation.
PMID- 26443220
TI - GeneKnockout by Targeted Mutagenesis in a Hemimetabolous Insect, the Two-Spotted
Cricket Gryllus bimaculatus, using TALENs.
AB - Hemimetabolous, or incompletely metamorphosing, insects are phylogenetically
basal. These insects include many deleterious species. The cricket, Gryllus
bimaculatus, is an emerging model for hemimetabolous insects, based on the
success of RNA interference (RNAi)-based gene-functional analyses and transgenic
technology. Taking advantage of genome-editing technologies in this species would
greatly promote functional genomics studies. Genome editing using transcription
activator-like effector nucleases (TALENs) has proven to be an effective method
for site-specific genome manipulation in various species. TALENs are artificial
nucleases that are capable of inducing DNA double-strand breaks into specified
target sequences. Here, we describe a protocol for TALEN-based gene knockout in
G. bimaculatus, including a mutant selection scheme via mutation detection
assays, for generating homozygous knockout organisms.
PMID- 26443221
TI - Methods for TALEN Evaluation, Use, and Mutation Detection in the Mosquito Aedes
aegypti.
AB - The generation and study of transgenic Aedes aegypti mosquitoes provides an
essential tool for elucidating the complex molecular biology of this important
vector. Within the field, genetic manipulation has surpassed the proof of
principle stage and is now utilized in both applied and theoretical vector
control strategies. The application of new instruments, technologies and
techniques allows ever more controlled experiments to be conducted. In this text
we describe microinjection of Ae. aegypti embryos in the context of evaluating
and performing genomic editing with transcription activator-like effector
nucleases (TALENs).
PMID- 26443222
TI - Methods for TALEN-Mediated Genomic Manipulations in Drosophila.
AB - TALEN (transcription activator-like effector nuclease) is a powerful tool for
gene disruption and other genomic modifications. In the past 3 years or so, it
has attracted eyes from every corner of the biological world, due to its
characteristics of simplicity, high efficiency, low toxicity, and applicability
across almost all species. In our lab, we first reported the TALEN-mediated gene
disruption in Drosophila, and recently employed this technique in precisely
modifying the Drosophila genome, such as in vivo tagging and gene correction.
Here, we describe in detail the protocols and experiences in TALEN-mediated
genomic modifications to share with the Drosophilists all over the world.
PMID- 26443223
TI - Targeted Mutagenesis in Zebrafish by TALENs.
AB - Zebrafish is a valuable model organism to study vertebrate development, organ
regeneration and to generate human disease models. As an important member of the
arsenal of genome editing, TALE nucleases (TALENs) have implicated in broad
applications in zebrafish reverse genetic studies. In this chapter, we describe
the detailed protocols of TALEN-mediated genome manipulations in zebrafish,
including targeted gene disruption by indel mutations, deletion of large genomic
regions by using two pairs of TALENs, and precise genome modification by
homologous recombination (HR).
PMID- 26443224
TI - Mutagenesis in Xenopus and Zebrafish using TALENs.
AB - Transcription activator-like effector nucleases (TALENs) have been proven to be
effective for gene specific targeting across species. Here we describe the
validated protocol for TALEN assembly as well as methods for generating gene
knockout animals of Xenopus and zebrafish. This protocol covers selection of
TALEN targeting sites, TALEN assembly with a modified Golden Gate method,
injection of TALEN mRNAs into Xenopus and zebrafish embryos as well as the
detection of somatic and germ-line transmitted mutations. Finally, the
establishment of knockout Xenopus and zebrafish lines is also described. This
protocol will facilitate broader applications of TALENs in developmental biology.
PMID- 26443225
TI - Genome Editing in Mice Using TALE Nucleases.
AB - Gene engineering for generating targeted mouse mutants is a key technology for
biomedical research. Using TALENs as sequence-specific nucleases to induce
targeted double-strand breaks, the mouse genome can be directly modified in
zygotes in a single step without the need for embryonic stem cells. By embryo
microinjection of TALEN mRNAs and targeting vectors, knockout and knock-in
alleles can be generated fast and efficiently. In this chapter we provide
protocols for the application of TALENs in mouse zygotes.
PMID- 26443226
TI - Genome Editing in Rats Using TALE Nucleases.
AB - The rat is an important animal model to understand gene function and model human
diseases. Since recent years, the development of gene-specific nucleases has
become important for generating new rat models of human diseases, to analyze the
role of genes and to generate human antibodies. Transcription activator-like
(TALE) nucleases efficiently create gene-specific knockout rats and lead to the
possibility of gene targeting by homology-directed recombination (HDR) and
generating knock-in rats. We describe a detailed protocol for generating knockout
and knock-in rats via microinjection of TALE nucleases into fertilized eggs. This
technology is an efficient, cost- and time-effective method for creating new rat
models.
PMID- 26443227
TI - Designer Nuclease-Mediated Generation of Knockout THP1 Cells.
AB - Recent developments in the field of designer nucleases allow the efficient and
specific manipulation of genomic architectures in eukaryotic cell lines. To this
end, it has become possible to introduce DNA double strand breaks (DSBs) at user
defined genomic loci. If located in critical coding regions of genes, thus
induced DSBs can lead to insertions or deletions (indels) that result in
frameshift mutations and thereby the knockout of the target gene. In this
chapter, we describe a step-by-step workflow for establishing knockout cell
clones of the difficult-to-transfect suspension cell line THP1. The here
described protocol encompasses electroporation, cell cloning, and a deep
sequencing-based genotyping step that allows the in-parallel analysis of 96 cell
clones per gene of interest. Furthermore, we describe the use of the analysis
tool OutKnocker that allows rapid identification of cell clones with all-allelic
frameshift mutations.
PMID- 26443228
TI - A systematic review of predictors and moderators of improvement in cognitive
behavioral therapy for panic disorder and agoraphobia.
AB - BACKGROUND: Despite the considerable efficacy of cognitive-behavioral therapy
(CBT) for panic disorder (PD) and agoraphobia, a substantial minority of patients
fail to improve for reasons that are poorly understood. OBJECTIVE: The aim of
this study was to identify consistent predictors and moderators of improvement in
CBT for PD and agoraphobia. DATA SOURCES: A systematic review and meta-analysis
of articles was conducted using PsycInfo and PubMed. Search terms included panic,
agoraphobi*, cognitive behavio*, CBT, cognitive therapy, behavio* therapy, CT,
BT, exposure, and cognitive restructuring. STUDY SELECTION: Studies were limited
to those employing semi-structured diagnostic interviews and examining change on
panic- or agoraphobia-specific measures. DATA EXTRACTION: The first author
extracted data on study characteristics, prediction analyses, effect sizes, and
indicators of study quality. Interrater reliability was confirmed. SYNTHESIS: 52
papers met inclusion criteria. Agoraphobic avoidance was the most consistent
predictor of decreased improvement, followed by low expectancy for change, high
levels of functional impairment, and Cluster C personality pathology. Other
variables were consistently unrelated to improvement in CBT, understudied, or
inconsistently related to improvement. LIMITATIONS: Many studies were
underpowered and failed to report effect sizes. Tests of moderation were rare.
CONCLUSIONS: Apart from agoraphobic avoidance, few variables consistently predict
improvement in CBT for PD and/or agoraphobia across studies.
PMID- 26443229
TI - Structure of P3HT crystals, thin films, and solutions by UV/Vis spectral
analysis.
AB - Optical absorption spectra of poly(3-hexylthiophene) (P3HT) are calculated in
solution, spin-coated thin films, and the bulk crystal using a multiscale
simulation approach. The structure of the amorphous thin film is obtained from
coarse grained molecular dynamics (MD) simulations and subsequent back-mapping
onto an atomistic force field representation. The absorption spectra are computed
using TDDFT by statistically averaging over an ensemble of molecules taken from
the MD simulations. Experimental UV/Vis spectra of spin-coated thin films and
solutions are recorded with varying ratios of 'good' versus 'poor' solvent. The
theoretical approach is able to faithfully predict the spectral position in the
various phases and offers fundamental insight into the cause of any spectral
shifts. The position of the main absorption peak is found to be chiefly
determined by the level of torsion between the thiophene rings inside each
molecule, while intermolecular effects are less important. Hence, optical
absorption spectra hold valuable clues about the microscopic structure of
disordered P3HT phases.
PMID- 26443230
TI - Paraneoplastic fasciitis and polyarthritis syndrome as a manifestation of breast
cancer recurrence in a BRCA1 gene-positive patient.
PMID- 26443231
TI - Ultra-high-resolution 3D digitalized imaging of the cerebral angioarchitecture in
rats using synchrotron radiation.
AB - The angioarchitecture is a fundamental aspect of brain development and
physiology. However, available imaging tools are unsuited for non-destructive
cerebral mapping of the functionally important three-dimensional (3D) vascular
microstructures. To address this issue, we developed an ultra-high resolution 3D
digitalized angioarchitectural map for rat brain, based on synchrotron radiation
phase contrast imaging (SR-PCI) with pixel size of 5.92 MUm. This approach
provides a systematic and detailed view of the cerebrovascular anatomy at the
micrometer level without any need for contrast agents. From qualitative and
quantitative perspectives, the present 3D data provide a considerable insight
into the spatial vascular network for whole rodent brain, particularly for
functionally important regions of interest, such as the hippocampus, pre-frontal
cerebral cortex and the corpus striatum. We extended these results to synchrotron
based virtual micro-endoscopy, thus revealing the trajectory of targeted vessels
in 3D. The SR-PCI method for systematic visualization of cerebral
microvasculature holds considerable promise for wider application in life
sciences, including 3D micro-imaging in experimental models of neurodevelopmental
and vascular disorders.
PMID- 26443232
TI - Dermal Fenestration With Negative Pressure Wound Therapy: A Technique for
Managing Soft Tissue Injuries Associated With High-Energy Complex Foot Fractures.
AB - Military casualties can sustain complex foot fractures from blast incidents. This
frequently involves the calcaneum and is commonly associated with mid-foot
fracture dislocations. The foot is at risk of both compartment syndrome and the
development of fracture blisters after such injuries. The amount of energy
transfer and the environment in which the injury was sustained also predispose
patients to potential skin necrosis and deep infection. Decompression of the
compartments is a part of accepted practice in civilian trauma to reduce the risk
of complications associated with significant soft tissue swelling. The
traditional methods of foot fasciotomy, however, are not without significant
complications. We report a simple technique of dermal fenestration combined with
the use of negative pressure wound therapy, which aims to preserve the skin
integrity of the foot without resorting to formal fasciotomy.
PMID- 26443233
TI - Characteristics of frozen epididymal spermatozoa from stallions that died 12 to
36 hours after colic surgery.
AB - Equine spermatozoa from the cauda epididymis were previously collected and
frozen, and the fertility was assessed. Most studies were performed on healthy
stallions that had undergone routine castration or on the epididymis collected at
the abattoir, but there are no studies on the quality of epididymal semen in
subjects which have died from colic or which underwent intensive care. The
present study was designed to verify whether a severe illness could affect
epididymal semen quality and freezability in the stallion. Therefore, epididymal
semen characteristics during the freezing process in stallions which had died
from colic and in healthy stallions submitted to elective castration were
compared. Five stallions that had died from colic (ill stallions [ISs]) and seven
stallions that had undergone elective castration (healthy stallions) were
castrated, and cauda epididymis spermatozoa were collected and processed. Sperm
quality was tested after collection, after washing procedures, at the end of the
equilibration (5 degrees C for 75 minutes), and after freezing/thawing. Sperm
quality was measured by objective motility characteristics, membrane and acrosome
integrity, and mitochondrial activity. After collection, sperm in ISs showed low
kinetic parameters (total motility: 17.3 +/- 3%, progressive motility: 6 +/- 1%,
average path velocity: 57.4 +/- 35.4 MUm/s, straightness: 74.2%) compared with
healthy stallions (total motility: 90.8 +/- 3.7%, progressive motility: 70 +/-
4%, average path velocity: 118.1 +/- 12.6 MUm/s, straightness: 82.4%) but
demonstrated similar membrane and acrosome integrity (85 +/- 2.8% vs. 87.6 +/-
3.1%). Sperm kinetic parameters increased after washing procedures and cooling in
ISs, reaching comparable values after equilibration (5 degrees C for 75 minutes)
and freezing/thawing. The data reported in this study suggest that the quality of
the equine epididymal spermatozoa cryopreserved in stallions that had died from
colic was similar to that reported in epididymal sperm after elective castration
and was also similar to the data reported in literature for cryopreserved equine
semen.
PMID- 26443234
TI - A phosphodiesterase type-5 inhibitor, sildenafil, induces sperm capacitation and
penetration into porcine oocytes in a chemically defined medium.
AB - The present study was undertaken to determine the effect of a phosphodiesterase
(PDE) type-5 (cyclic guanosine monophosphate-specific) inhibitor, sildenafil, on
capacitation and penetration of boar spermatozoa in a basic chemically defined
medium (adenosine- and theophylline-free PGM-tac4). When ejaculated spermatozoa
were cultured for 90 minutes in the absence or presence of sildenafil at 2.5 mM,
the inhibitor significantly increased the percentage of capacitated/acrosome
reacted spermatozoa, as a result of the chlortetracycline assay. When fresh
spermatozoa were co-cultured with oocytes in the presence of sildenafil at a
different concentration (0, 2.5, 25, or 250 MUM), higher sildenafil
concentrations (25 and 250 MUM) significantly resulted in higher sperm
penetration rates. When oocytes matured in vitro were co-cultured with
spermatozoa in the presence of 25 MUM sildenafil or 25 mM caffeine benzoate for 8
hours, the incidence of penetrated oocytes did not differ between two groups,
whereas the incidence of monospermic oocytes in penetrated one was significantly
higher in the presence of sildenafil. Immunocytochemical analysis reported the
presence of PDE type-5 on the acrosome region of boar spermatozoa. These results
report that regulation of cyclic guanosine monophosphate-specific PDE type-5 by
sildenafil somehow can increase the penetrability of boar spermatozoa in vitro.
PMID- 26443235
TI - Effect of early pregnancy diagnosis by per rectum amniotic sac palpation on
pregnancy loss, calving rates, and abnormalities in newborn dairy calves.
AB - The objectives of the present study were to evaluate the effect of per rectal
amniotic sac palpation (ASP) for pregnancy diagnosis during the late embryonic
period on pregnancy loss, calving rates, and abnormalities in newborn calves. A
controlled, randomized, blocked, blind experiment containing 680 lactating
pregnant dairy cows with a viable embryo diagnosed by transrectal ultrasonography
was performed. Two dairy operation sites (farm A and farm B) were selected. At
each farm, the cows were randomly divided into control (CON) and ASP groups. The
CON group was not subjected to pregnancy diagnosis via per rectum palpation. The
ASP examinations were performed by one experienced veterinarian between Days 34
and 45 after breeding. All cows were reevaluated by transrectal ultrasonography
only between 2 and 4 weeks later. Two calving rates were calculated: calving rate
1 (cows that calved from the initial number of pregnant cows) and calving rate 2
(cows that calved from cows pregnant at reexamination). In farm A, the
percentages of early pregnancy loss were 11.5% (19 of 165) and 13.2% (24 of 182)
for the CON and the ASP groups, respectively (P = 0.64). In farm B, the
percentage of early pregnancy loss was 11.2% (19 of 170) for the CON group and
8.8% (14 of 159; P = 0.48) for the ASP group. In farm A, the percentage of late
pregnancy loss was 7.6% (11 of 145) for the CON group and 5.5% (8 of 155; P =
0.39) for the ASP group. In farm B, the percentage of late pregnancy loss was
3.7% (5 of 137) for the CON group and 6.3% (8 of 127; P = 0.32) for the ASP
group. In farm A, early pregnancy loss was higher than late pregnancy loss (12.4%
vs. 6.3%; P = 0.01), and in farm B, the same tendency was detected (10.0% vs.
4.9%, for early and late pregnancy loss, respectively; P = 0.02). In farm A,
calving rate 1 was 81.2% (134 of 165) for the CON group and 80.8% (147 of 182; P
= 0.92) for the ASP group. Calving rate 2 for the same groups was 92.4% (134 of
145) and 94.8% (147 of 155), respectively (P = 0.68). In farm B, calving rate 1
was 77.7% (132 of 170) for the CON group and 74.8% (119 of 159; P = 0.55) for the
ASP group. Calving rates 2 for the same groups were 87.4% (132 of 151) and 82.1%
(119 of 145), respectively (P = 0.20). Two female calves with atresia coli were
diagnosed only in the CON group. It was concluded that ASP during the late
embryonic period for pregnancy diagnosis did not increase the pregnancy loss,
affect calving rates, or produce abnormalities in calves.
PMID- 26443237
TI - A clinical survey of pain in Parkinson's disease in Eastern China.
AB - BACKGROUND: This is a case-control study to investigate the prevalence,
characteristics, and risk factors of pain in patients with Parkinson's disease
(PD). METHODS: A total of 200 PD patients from eastern China were enrolled in our
study. Accordingly, 200 healthy elderly adults were recruited as controls. The
characteristics of pain were collected by using the Visual Analog Scale, Brief
Pain Inventory (BPI), SF-36 Bodily Pain Scale, Unified Parkinson's Disease Rating
Scale, Hoehn-Yahr Scale (H-Y), Hamilton Depression Scale, and Leeds Assessment of
Neuropathic Symptoms and Signs. RESULTS: Of the 200 PD patients, pain was
complained by 106 patients (53%). According to the SF-36 Bodily Pain Scale, pain
morbidity in PD patients was significantly higher than in the control group. The
average pain during last 24 h measured by the BPI was 2.67. About 76% of PD
patients were found to have one pain type, 21.7% were having two pain types, and
1.9% had three pain types. Further, 69.8% of these patients were presented with
musculoskeletal pain, 4.7% with dystonic pain, 22.6% with radicular-neuropathic
pain, 20.8% with central neuropathic pain, and 9.4% with akathisia pain. The
onset age and depression were the most significant predictors of pain in PD
patients (p < 0.05). However, there was no significant association between pain
and gender, age, disease duration, or severity of the disease. Only 5.7% of PD
patients with pain received treatment in this study. CONCLUSIONS: Pain is
frequent and disabling, independent of demographic and clinical variables, and is
significantly more common in PD patients.
PMID- 26443236
TI - Neural Correlates of Self and Its Interaction With Memory in Healthy Adolescents.
AB - Adolescence is marked by the development of personal identity and is associated
with structural and functional changes in brain regions associated with Self
processing. Yet, little is known about the neural correlates of self-reference
processing and self-reference effect in adolescents. This functional magnetic
resonance imaging study consists of a self-reference paradigm followed by a
recognition test proposed to 30 healthy adolescents aged 13-18 years old. Results
showed that the rostral anterior cingulate cortex is specifically involved in
self-reference processing and that this specialization develops gradually from 13
to 18 years old. The self-reference effect is associated with increased brain
activation changes during encoding, suggesting that the beneficial effect of Self
on memory may occur at encoding of self-referential information, rather than at
retrieval.
PMID- 26443238
TI - Modulation of intestinal calcium and phosphate transport in young goats fed a
nitrogen- and/or calcium-reduced diet.
AB - Feeding ruminants a reduced N diet is a common approach to reduce N output based
on rumino-hepatic circulation. However, a reduction in N intake caused massive
changes in Ca and inorganic phosphate (Pi) homoeostasis in goats. Although a
single dietary Ca reduction stimulated intestinal Ca absorption in a calcitriol
dependent manner, a concomitant reduction of Ca and N supply led to a decrease in
calcitriol, and therefore a modulation of intestinal Ca and Pi absorption. The
aim of this study was to examine the potential effects of dietary N or Ca
reduction separately on intestinal Ca and Pi transport in young goats. Animals
were allocated to a control, N-reduced, Ca-reduced or combined N- and Ca-reduced
diet for about 6-8 weeks, whereby N content was reduced by 25 % compared with
recommendations. In Ussing chamber experiments, intestinal Ca flux rates
significantly decreased in goats fed a reduced N diet, whereas Pi flux rates were
unaffected. In contrast, a dietary Ca reduction stimulated Ca flux rates and
decreased Pi flux rates. The combined dietary N and Ca reduction withdrew the
stimulating effect of dietary Ca reduction on Ca flux rates. The expression of Ca
transporting proteins decreased with a reduced N diet too, whereas Pi
transporting proteins were unaffected. In conclusion, a dietary N reduction
decreased intestinal Ca transport by diminishing Ca-transporting proteins, which
became clear during simultaneous N and Ca reduction. Therefore, N supply in young
ruminant nutrition is of special concern for intestinal Ca transport.
PMID- 26443239
TI - Mobile in Situ Simulation as a Tool for Evaluation and Improvement of Trauma
Treatment in the Emergency Department.
AB - BACKGROUND: Medical simulation is an increasingly recognized tool for teaching,
coaching, training, and examining practitioners in the medical field. For many
years, simulation has been used to improve trauma care and teamwork. Despite
technological advances in trauma simulators, including better means of
mobilization and control, most reported simulation-based trauma training has been
conducted inside simulation centers, and the practice of mobile simulation in
hospitals' trauma rooms has not been investigated fully. METHODS: The emergency
department personnel from a second-level trauma center in Israel were evaluated.
Divided into randomly formed trauma teams, they were reviewed twice using in situ
mobile simulation training at the hospital's trauma bay. In all, 4 simulations
were held before and 4 simulations were held after a structured learning
intervention. The intervention included a 1-day simulation-based training
conducted at the Israel Center for Medical Simulation (MSR), which included video
based debriefing facilitated by the hospital's 4 trauma team leaders who
completed a 2-day simulation-based instructors' course before the start of the
study. The instructors were also trained on performance rating and thus were
responsible for the assessment of their respective teams in real time as well as
through reviewing of the recorded videos; thus enabling a comparison of the
performances in the mobile simulation exercise before and after the educational
intervention. RESULTS: The internal reliability of the experts' evaluation
calculated in the Cronbach alpha model was found to be 0.786. Statistically
significant improvement was observed in 4 of 10 parameters, among which were
teamwork (29.64%) and communication (24.48%) (p = 0.00005). CONCLUSION: The
mobile in situ simulation-based training demonstrated efficacy both as an
assessment tool for trauma teams' function and an educational intervention when
coupled with in vitro simulation-based training, resulting in a significant
improvement of the teams' function in various aspects of treatment.
PMID- 26443240
TI - PKA antagonizes CLASP-dependent microtubule stabilization to re-localize Pom1 and
buffer cell size upon glucose limitation.
AB - Cells couple growth with division and regulate size in response to nutrient
availability. In rod-shaped fission yeast, cell-size control occurs at mitotic
commitment. An important regulator is the DYRK-family kinase Pom1, which forms
gradients from cell poles and inhibits the mitotic activator Cdr2, itself
localized at the medial cortex. Where and when Pom1 modulates Cdr2 activity is
unclear as Pom1 medial cortical levels remain constant during cell elongation.
Here we show that Pom1 re-localizes to cell sides upon environmental glucose
limitation, where it strongly delays mitosis. This re-localization is caused by
severe microtubule destabilization upon glucose starvation, with microtubules
undergoing catastrophe and depositing the Pom1 gradient nucleator Tea4 at cell
sides. Microtubule destabilization requires PKA/Pka1 activity, which negatively
regulates the microtubule rescue factor CLASP/Cls1/Peg1, reducing CLASP's ability
to stabilize microtubules. Thus, PKA signalling tunes CLASP's activity to promote
Pom1 cell side localization and buffer cell size upon glucose starvation.
PMID- 26443241
TI - Robot-assisted laparoscopic management of duplex renal anomaly: Comparison of
surgical outcomes to traditional pure laparoscopic and open surgery.
AB - INTRODUCTION: Surgical management of duplex renal anomaly (DRA) is complex
because of individual anatomic variation, competing priorities of vesicoureteral
reflux (VUR) and ureteral obstruction present in the same child, the varied
differential function of the different renal moieties, and the presence of
voiding dysfunction and recurrent urinary tract infection (UTI). Robot-assisted
laparoscopic (RAL) surgical management has been under-reported in this group of
children but is becoming a viable alternative to traditional open surgery.
OBJECTIVE: The aim was to report the surgical outcomes of a series of children
with DRA who had RAL surgery and compare these outcomes to historical cohorts of
open and laparoscopic surgery. STUDY DESIGN: This was a retrospective analysis of
a prospective series of children who had RAL surgery for DRA over an 8-year
period. Forty-five RAL surgeries were performed in 47 children. RAL
heminephrectomy (RAL HN) was performed in 19 children for poorly or non
functional renal moiety. One had staged bilateral RAL HN. RAL ureteroureterostomy
(RAL UU) was performed in 14 children for upper pole ureteral obstruction.
Thirteen RAL common sheath ureteral reimplants (RAL csUN) with or without
ureteral tapering were performed in 12 children with VUR and UTI. Diagnosis and
demographics, results of preoperative imaging, intraoperative time stamps,
perioperative complications, success rate, and renal outcomes were recorded.
RESULTS: Low-grade VUR present preoperatively in the RAL UU group all resolved
within the follow-up period. Four (25%) children in the RAL HN group developed de
novo VUR after surgery, which resolved in two (50%) and required surgery in two
(50%). Grade I VUR after RAL csUR that occurred in two (14.3%) children was
asymptomatic and observed when off preventative antibiotics. DISCUSSION: Most
children with DRA who need surgical treatment can be offered RAL surgery. We
report good outcomes and improved operative times for RAL HN and UU that approach
historical open and pure laparoscopic cohorts. However, RAL csUR, especially with
ureteral tapering, is more complex and inherently susceptible to complications,
and has not met the outcomes of the open gold standard. The limits of this study
are that selection bias is present, and there is no study control cohort.
CONCLUSIONS: This report achieves its aim to report surgical outcomes of children
who had RAL surgery for DRA.
PMID- 26443242
TI - Contrasting acute and chronic effects of tolvaptan on serum osmolality in the
EVEREST trial.
AB - AIMS: In the EVEREST trial, tolvaptan improved symptoms and body weight during
hospitalization for heart failure (HF), but did not improve post-discharge
cardiovascular outcomes. We hypothesized that this disconnect between the short-
and long-term effects may be related to changes in serum osmolality. We describe
the longitudinal profile of osmolality and its response to tolvaptan during and
after hospitalization for HF. METHODS AND RESULTS: EVEREST enrolled 4133 patients
hospitalized for HF and reduced EF. Serum osmolality data were available in 3744
(91%). We assessed the effects of tolvaptan on serum osmolality and related these
effects to in-hospital changes in body weight and physician-assessed symptoms.
Calculated values of osmolality, determined from serum sodium, blood urea
nitrogen, and glucose, were 3-4 mOsm/kg higher than concurrently measured serum
osmolality at enrolment and discharge in both treatment arms. During
hospitalization in the placebo group, serum osmolality slightly increased
throughout hospitalization, whereas serum sodium decreased and blood urea
nitrogen increased until discharge. Tolvaptan increased osmolality by hospital
day 1, but this effect diminished by post-discharge week 4-8 and disappeared by
post-discharge week 56. In-hospital changes in osmolality were poorly correlated
with in-hospital changes in body weight and physician-assessed dyspnoea.
CONCLUSION: Tolvaptan increased serum osmolality during hospitalization for HF, a
time frame when the drug also improved signs and symptoms of HF. However, this
effect on osmolality declined in the early post-discharge period, when tolvaptan
failed to influence clinical outcomes. Serum osmolality, which can be estimated
based on readily available laboratory parameters, may be a marker or a target of
response to tolvaptan.
PMID- 26443243
TI - New reconstruction of the Wiwaxia scleritome, with data from Chengjiang
juveniles.
AB - Wiwaxiids are a problematic group of scale-covered lophotrochozoans known from
Cambrian Stages 3-5. Their imbricating dorsal scleritome of leaf-like scales has
prompted comparison with various annelids and molluscs, and has been used as a
template to reconstruct the articulation pattern of isolated Small Shelly
Fossils. The first articulated specimens of Wiwaxia from the Cambrian Stage 3
Chengjiang Konservat-Lagerstatte show that the Wiwaxia scleritome comprised nine
equivalent transverse rows associated with outgrowths of soft tissue, but did not
possess a separate zone of anterior sclerites. This serial construction is
fundamentally incompatible with the circumferential disposition of sclerites in
early molluscs, but does closely resemble the armature of certain annelids. A
deep homology with the annelid scleritome must be reconciled with Wiwaxia's
mollusc-like mouthparts and foot; together these point to a deep phylogenetic
position, close to the common ancestor of annelids and molluscs.
PMID- 26443244
TI - Latest developments in allergic rhinitis in Allergy for clinicians and
researchers.
AB - Research efforts in allergic rhinitis have always been intense. Over the past 3
years, numerous breakthroughs in basic science and clinical research have been
made, augmenting our understanding of this condition that afflicts a significant
proportion of the global population. New epidemiological findings, novel insights
into the molecular and cellular mechanisms of allergy, enhancement of current
developmental theories, new concepts of the goals and endpoints of management,
and latest therapeutic modalities that includes the harnessing of information
technology and big data are some areas where important advances were made. We
attempt to bring you a summary of the key research advances made in the field of
allergic rhinitis from 2013 to 2015.
PMID- 26443245
TI - Equity Chasm in Megacities: Five Leading Causes of Death in Tehran.
AB - BACKGROUND: Inequity in megacities is a real concern in public health
perspective. Tehran is a megacity with more than 8 million population that is
divided into 22 regions (counties) with considerable diversity in socioeconomic
status. On the other hand, spatial cluster detection is an important tool in
disease surveillance to identify areas of elevated risk and to generate
hypotheses about disease or mortality etiology. The present research aims to
identify high or low-risk clusters for five non-communicable leading causes of
death in 22 regions of Tehran province. METHODS: Cause-specific mortality rates
were extracted from Behesht-e-Zahra registry system for Tehran province in 2011.
Spatial scan statistic as a most common method in spatial cluster detection was
chosen to detect clusters with elevated risk of death. Given the observed and
expected number death in each region, a log likelihood ratio (LLR) criterion was
used to test whether a cluster is significant. RESULT: Two high-risk and two low
risk clusters were detected for each cause of death. All these clusters were
statistically significant with P value less than 0.05. Mapping these clusters
shows substantial differences between regions in Tehran. For mortality due to
ischemic heart diseases, cerebrovascular diseases, hypertensive diseases,
respiratory diseases, and stomach cancer, the high-risk clusters concentrated in
southern half of Tehran and low-risk clusters were in northern half of Tehran. In
the most situations, regions 2, 3 and 5 seemed to have lower rate of death
comparing with other regions. On the other hand, regions, 16, 19 and 20 were in
the high rate clusters. CONCLUSION: There was substantial disparity between
regions of Tehran for five non-communicable causes of death studied in this
article. Identifying factors affecting the observed differences is useful to set
effective preventive interventions and can be investigated in future researches.
PMID- 26443246
TI - Burden of Cancers in Iran from 1990 to 2010: findings from the Global Burden of
Disease study 2010.
AB - BACKGROUND: Cancer is one of the most common non-communicable diseases in both
sexes and a major cause of disability and death around the world, as well as in
Iran. The aim of the present manuscript is to report the results of the Global
Burden of Disease study 2010 (the GBD 2010) to compare the results with the other
similar findings. The paper also discusses the existing deficiencies of the GBD
study. Our aim was to describe and criticize the attributed burden of cancers
according to the GBD results by sex and age. METHODS: The GBD 2010 has profited
from 100 collaborators worldwide and provides a vast network of data on health
outcomes, vital registries, and population surveys. The GBD has used various
scientific-approved methods to estimate important health statuses like death
rates, life expectancy, and healthy adjusted life expectancy, disability-adjusted
life years, years of living lost due to premature death and years of life with
disabilities. In the present study, we extracted and graphed the GBD results for
Iran in order to present a better scheme for readers. RESULTS: The mortality rate
of cancers in Iranians has increased by about 8.5%, the disability-adjusted life
year rates have declined by about 9%, and years lost due to premature death have
also decreased by about 10% from 1990 to 2010 compared to an 85% increase in
years of life with disabilities in the same time period. CONCLUSION: The burden
of all non-communicable diseases (NCDs) including cancers showed decrease during
the past two decades. However, these diseases still remain worldwide health
challenge. Prevention should be considered as an important priority and
responsibility. The health authorities also need to determine the burden of
cancers at the national and sub-national levels for implementation of effective
preventive strategies.
PMID- 26443247
TI - Identification of Genomic Species of Acinetobacter Isolated from Burns of ICU
Patients.
AB - BACKGROUND: The worldwide emergence of multi-drug resistant (MDR) bacteria in
recent years has caused many problems for hospitals and patients, especially
intensive care unit patients. Among these clinically important MDR bacteria are
Acinetobacter baumannii complex species (A. baumannii, Acinetobacter genomic
species 3 and Acinetobacter genomic species 13TU) that cause a wide range of
infections. METHODS: The sequencing and bioinformatics analysis of a part of the
Zone 1 of rpoB gene was performed for species identification of Acinetobacter
isolates obtained from ICU patients with infected burns hospitalized in a
hospital in Isfahan, Iran, over a 9-month period. Antibiotic sensitivity of
Acinetobacter isolates was investigated using the disk diffusion method and
different classes of antibiotics including amikacin, cefotaxime, ceftriaxone,
ciprofloxacin, imipenem and piperacillin. RESULTS: Acinetobacter spp. were
isolated from 10 of 80 (12.5%) investigated patients. All of the 10 Acinetobacter
isolates were identified as Acinetobacter baumannii and multi-drug resistant
according to antibiotic susceptibility tests. CONCLUSION: Of the Acinetobacter
baumannii complex members, only A. baumannii species was identified among the
isolates obtained from patients with infected burns in an Isfahan hospital over a
9-month period.
PMID- 26443248
TI - Carrier Testing in Known Autosomal Recessive Intellectual Disability Genes in an
Iranian Healthy Individual Using Exome Sequencing.
AB - BACKGROUND: Intellectual Disability (ID) is one of the most common disabling
impairments worldwide. Autosomal recessive ID (ARID), a genetically heterogeneous
disorder, is more common in countries such as Iran where the rate of
consanguineous marriages is high. Considering the social-economic burden of ARID
in our country, it is crucial to find out whether couples who are cousins are
carriers for disease causing mutations, in order to prevent the birth of an
affected child. METHODS: Using exome sequencing, we screened known ARID genes in
a normal individual to identify possible mutations in heterozygous form. RESULTS:
We identified four protein coding alleles which possibly affect protein function,
in different ID genes: PMM2, RBM28, SLC19A3, and VPS13B. CONCLUSION: These
findings can be used to prevent the birth of children with ARID by checking the
other partner for possible disease causing variants.
PMID- 26443249
TI - Exome Sequencing and Linkage Analysis Identified Novel Candidate Genes in
Recessive Intellectual Disability Associated with Ataxia.
AB - BACKGROUND: Intellectual disability (ID) is a neuro-developmental disorder which
causes considerable socio-economic problems. Some ID individuals are also
affected by ataxia, and the condition includes different mutations affecting
several genes. METHODS: We used whole exome sequencing (WES) in combination with
homozygosity mapping (HM) to identify the genetic defects in five consanguineous
families among our cohort study, with two affected children with ID and ataxia as
major clinical symptoms. RESULTS: We identified three novel candidate genes,
RIPPLY1, MRPL10, SNX14, and a new mutation in known gene SURF1. All are autosomal
genes, except RIPPLY1, which is located on the X chromosome. Two are housekeeping
genes, implicated in transcription and translation regulation and intracellular
trafficking, and two encode mitochondrial proteins. The pathogenesis of these
variants was evaluated by mutation classification, bioinformatic methods, review
of medical and biological relevance, co-segregation studies in the particular
family, and a normal population study. CONCLUSIONS: Linkage analysis and exome
sequencing of a small number of affected family members is a powerful new
technique which can be used to decrease the number of candidate genes in
heterogenic disorders such as ID, and may even identify the responsible gene(s).
PMID- 26443250
TI - Impact of KIF6 Polymorphism rs20455 on Coronary Heart Disease Risk and
Effectiveness of Statin Therapy in 100 Patients from Southern Iran.
AB - BACKGROUND: The purpose of this study was to investigate the association between
Trp719Arg (rs20455) and Coronary Heart Disease (CHD), and also Coronary Heart
Disease reduction in individuals with this SNP during statin therapy in southern
Iran. It has been shown that rs20455, which could affect the function of kinesin
protein, is associated with Coronary Heart Disease and could be an effective
factor for patients who take statin therapy. METHODS: Patients and control
individuals were genotyped for rs20455 Single Nucleotide Polymorphism (SNP) using
ARMS PCR (Amplification Refractory Mutation System Polymerase Chain Reaction) and
RFLP (Restriction Fragment Length Polymorphism) analysis. The effect of kinesin
family member 6 (KIF6) on statin therapy was also examined among patients who had
a history of one or two heart attacks. RESULTS: It was found that rs20455 had a
significant association with Coronary Heart Disease (Odds Ratio [OR] 3.17, 95%
Confidence Interval [CI] 1.68 to 5.98). In addition, statin therapy was more
effective in rs20455 carriers than non-carriers, with 80% of the carriers showed
positive response to this treatment. CONCLUSIONS: Trp 719Arg have an effect on
development of Coronary Heart Disease but it is very useful for statin therapy.
Overall, individuals with this Single Nucleotide Polymorphism can take statin
therapy to prevent the catastrophic consequences of Coronary Heart Disease.
PMID- 26443251
TI - Genetic Investigation of an Iranian Supercentenarian by Whole Exome Sequencing.
AB - BACKGROUND: The genetic basis of longevity is an important field of study because
the majority of supercentenarian cases experience healthy aging and may only show
age-related diseases in their last few years of life. It is clear that genetic
factors play an important role in survival beyond 90 years of age, but the exact
relationship of genetic variants to this phenomenon remains unknown. OBJECTIVE:
The aim of this project was to investigate different hypotheses that describe the
relationship between genetic variants and human longevity in a living Iranian man
by Whole Exome Sequencing. METHODS: Initially, we conducted high quality DNA
extraction on a peripheral blood sample. Then, whole exome sequencing was
performed on the DNA and different bioinformatic software packages and databases
were used to analyze the data. Tertiary analysis was performed on four genetic
hypotheses for longevity. RESULTS: Analysis showed that among 27 metabolic
variants which are related to longevity, 18 variants encompassed the exceptional
longevity allele. In comparison with the NHGRI GWAS catalog, the case had 58
trait-associated variants of which 11 were homozygous for the risk allele. We
also discovered 25 novel variants within candidate genes for aging and longevity
and we detected seven longevity-associated variants in the sample. CONCLUSION:
This study was performed on just one sample and so the results cannot be
interpreted as a generalized principle for other elderly societies, but this is
the first step towards investigation of the genetic basis of longevity in Iran
and provides an insight for further studies in the field of longevity.
PMID- 26443252
TI - Analysis of HLA-DQB1*0602 in Multiple Sclerosis Patients in Khuzestan Province,
Iran.
AB - BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune and
also complex disease of the central nervous system the etiology of which is not
completely defined; but both genetic and environmental factors are regarded as
main factors in its susceptibility. HLA-DQB1*0602 is considered as one of the
most important genetic factors in MS predisposition but contradictory results
have been reported in different populations world-wide. Since there are no data
with respect to the correlation of HLA-DQB1*0602 and multiple sclerosis in
Khuzestan province, and because of ethnic diversity in Khuzestan province, the
aim was to examine the association of this allele with multiple sclerosis in
Khuzestan. METHODS: This is a case control study that evaluated 200 MS patients
from Khuzestan and 200 healthy individuals from the same geographical region. DNA
extraction was performed by salting out method; in addition, HLA typing was
carried out by polymerase chain reaction amplification with sequence-specific
primers (PCR-SSP) method. The present study also considered probable association
among HLA-DQB1*0602 with sex, ethnicity, and type of disease. RESULTS: Results
revealed that distribution of mentioned allele was not statistically different
among cases and controls (61.5% vs. 64%, P = 0.605); furthermore, no association
was shown between this allele and gender, ethnicity or type of disease.
CONCLUSION: On the whole, our result is consistent with most of the other studies
in Iran; but contrasts with most of the studies in European populations.
PMID- 26443253
TI - Comparison of Oral Lichen Planus and Systemic Lupus Erythematosus in Interleukins
Level.
AB - Lichen planus (LP) is a chronic inflammatory mucocutaneous disorder with unknown
etiology. Systemic lupus erythematosus (SLE) is known as a prototypic autoimmune
disease. Cytokines play a key role in the pathogenesis of both diseases. Various
cytokines, such as interleukin 6 (IL-6), interleukin 10 (IL-10), interferon alpha
(INF-a), and Tumor Necrosis Factor-alpha (TNF-a) can serve as biomarkers to
predict SLE severity and monitor disease activity. In this review, we compare
interleukins in oral lichen planus and lupus erythematosus as an autoimmune
disease prototype. So, this review may provide insight for researchers in
completing the cytokine network in OLP. Among the etiologic factors, the
imbalance between Th-1 and Th-2 cytokine production plays an important role in
the development of both diseases. By understanding cytokines and immunoregulatory
networks of cytokines in these patients, appropriate treatment can be offered.
There are many limitations in cytokine studies, which we have described in this
article.
PMID- 26443254
TI - Statistical Issues in Estimation of Adjusted Risk Ratio in Prospective Studies.
AB - BACKGROUND: Binary outcomes are common in prospective studies such as randomized
controlled trials and cohort studies. Logistic regression is the most popular
regression model for binary outcomes. Logistic regression yields an odds ratio
that approximates the risk ratio when the risk of outcome is low. A consensus has
been reached in an extensive argument in much of the literature that the risk
ratio is preferred over the odds ratio for prospective studies. To obtain a model
based estimate of risk ratios, log-binomial regression has been recommended.
However, this model may fail to converge and many methods have been provided as
an alternative in these situations. METHODS: In this paper, we discuss the
methods to obtain adjusted risk ratios in settings with independent and clustered
data and we will review the results of comparisons between these methods based on
simulation studies, especially a large simulation study which was conducted by
the authors. We use hypothetical examples to show how log-Poisson regression with
modified standard errors can be used to estimate risk ratio in practice using
popular statistical software. CONCLUSION: The potential misinterpretation of odds
ratios should be considered by researchers, especially when the risk of the
outcome is high. When researchers want to estimate the effect of exposure or
intervention by controlling potential covariates, the misinterpretation of odds
ratios can be avoided using regression models that can estimate risk ratios
instead of logistic regression. The log-Poisson regression with modified standard
errors can be considered to estimate risk ratios in both independent and
clustered data settings.
PMID- 26443255
TI - Hypercalcemia and Lytic Bone Lesions Masquerading Inflammatory Arthritis Treated
as Rheumatoid Arthritis.
AB - Hyperparathyroidism is a complex clinical syndrome characterized by dysfunction
in the metabolism of bone, calcium and phosphorus. Rheumatologic manifestations
are common amongst patients with hyperparathyroidism. We report a 50-year-old
woman with hypercalcemia, lytic bone lesions and inflammatory arthritis of both
hands that were not resolved after parathyroidectomy. Laboratory evidence of
elevated erythrocyte sedimentation rate, positive C-reactive protein (CRP) and
high titers of anti-CCP and rheumatoid factor was diagnostic of rheumatoid
arthritis (RA) according to European League Against Rheumatism criteria.
Eventually, with the concomitant diagnoses of hyperparathyroidism and RA, she was
treated with methotrexate and hydroxychloroquin. Hyperparathyroidism may present
with rheumatologic manifestations, leading to an initial misdiagnosis.
Furthermore, attention to this fact that hypercalcemia is not commonly associated
with RA, and rather suggestive of a concomitant disorder, is crucial to the
diagnosis of hyperparathyroidism in RA patients with hypercalcemia.
PMID- 26443256
TI - Acute Severe Hepatitis and Hemophagocytosis in Adult Onset Still's Disease.
AB - We report a 44-year-old male Turkish patient with adult onset Still's disease
(AOSD) complicated by acute severe hepatitis and hemophagocytosis. Initial
investigations for fever and rapidly progressive elevation of liver function
tests were not diagnostic. Routine evaluations of liver and bone marrow biopsies
missed the fundamental pathology. Extremely elevated ferritin levels led to a
more detailed search, and immunohistochemical staining with CD68 for macrophages
revealed extensive hemophagocytosis in both the first and second bone marrow
biopsies, as well as in the liver biopsy. Treatment with steroid and cyclosporine
A induced complete remission.
PMID- 26443257
TI - Professor Kamaleddin Armin (1914-1995); a Superb Mentor with High Morals.
PMID- 26443258
TI - The Oldest Recorded Case of Acromegaly and Gigantism in Iran.
AB - Here we commemorate the character and academic authority of Prof. Zabiholah
Gorban (1903-2006), the founder of Shiraz medical school. No doubt, in the scope
of history of contemporary medicine, he has been efficient and effective. With
respect to this fact, his article on a rare case described in Acta anatomica
published in Iran in 1966, entitled (Observations on a giant skeleton) is browsed
and reviewed. A case named Siah Khan with combined acromegaly and gigantism that
appears to have letters to say still after nearly half a century.
PMID- 26443259
TI - Dr. Nasser Moeinzadeh (1930-2015); A Pioneering Otolaryngologist in Iran.
PMID- 26443260
TI - Chest Wall and Spinal Tuberculous Abscess.
PMID- 26443261
TI - Unlocking the potential of lignocellulosic biomass through plant science.
AB - The aim of producing sustainable liquid biofuels and chemicals from
lignocellulosic biomass remains high on the sustainability agenda, but is
challenged by the costs of producing fermentable sugars from these materials.
Sugars from plant biomass can be fermented to alcohols or even alkanes, creating
a liquid fuel in which carbon released on combustion is balanced by its
photosynthetic capture. Large amounts of sugar are present in the woody, nonfood
parts of crops and could be used for fuel production without compromising global
food security. However, the sugar in woody biomass is locked up in the complex
and recalcitrant lignocellulosic plant cell wall, making it difficult and
expensive to extract. In this paper, we review what is known about the major
polymeric components of woody plant biomass, with an emphasis on the molecular
interactions that contribute to its recalcitrance to enzymatic digestion. In
addition, we review the extensive research that has been carried out in order to
understand and reduce lignocellulose recalcitrance and enable more cost-effective
production of fuel from woody plant biomass.
PMID- 26443262
TI - Differential Many-Body Cooperativity in Electronic Spectra of Oligonuclear
Transition-Metal Complexes.
AB - In computational chemistry, non-additive and cooperative effects can be defined
in terms of a (differential) many-body expansion of the energy or any other
physical property of the molecular system of interest. One-body terms describe
energies or properties of the subsystems, two-body terms describe non-additive
but pairwise contributions and three-body as well as higher-order terms can be
interpreted as a measure for cooperativity. In the present article, this concept
is applied to the analysis of ultraviolet/visible (UV/Vis) spectra of
homotrinuclear transition-metal complexes by means of a many-body expansion of
the change in the spectrum induced by replacing each of the three transition
metal ions by another transition-metal ion to yield a different homotrinuclear
transition-metal complex. Computed spectra for the triangulo-complexes [M3
{Si(mt(Me) )3}2] (M=Pd/Pt, mt(Me) =methimazole) and tritopic triphenylene-based N
heterocyclic carbene Rh/Ir complexes illustrate the concept, showing large and
small differential three-body cooperativity, respectively.
PMID- 26443263
TI - 3D stereolithography printing of graphene oxide reinforced complex architectures.
AB - Properties of polymer based nanocomposites reply on distribution, concentration,
geometry and property of nanofillers in polymer matrix. Increasing the
concentration of carbon based nanomaterials, such as CNTs, in polymer matrix
often results in stronger but more brittle material. Here, we demonstrated the
first three-dimensional (3D) printed graphene oxide complex structures by
stereolithography with good combination of strength and ductility. With only 0.2%
GOs, the tensile strength is increased by 62.2% and elongation increased by
12.8%. Transmission electron microscope results show that the GOs were randomly
aligned in the cross section of polymer. We investigated the strengthening
mechanism of the 3D printed structure in terms of tensile strength and Young's
modulus. It is found that an increase in ductility of the 3D printed
nanocomposites is related to increase in crystallinity of GOs reinforced polymer.
Compression test of 3D GOs structure reveals the metal-like failure model of GOs
nanocomposites.
PMID- 26443264
TI - Adherence to Antiretroviral Therapy Among Children Living with HIV in South
India.
AB - Adherence to ART, fundamental to treatment success, has been poorly studied in
India. Caregivers of children attending HIV clinics in southern India were
interviewed using structured questionnaires. Adherence was assessed using a
visual analogue scale representing past-month adherence and treatment
interruptions >48 h during the past 3 months. Clinical features, correlates of
adherence and HIV-1 viral-load were documented. Based on caregiver reports, 90.9
% of the children were optimally adherent. In multivariable analysis,
experiencing ART-related adverse effects was significantly associated with
suboptimal adherence (p = 0.01). The proportion of children who experienced
virological failure was 16.5 %. Virological failure was not linked to suboptimal
adherence. Factors influencing virological failure included running out of
medications (p = 0.002) and the child refusing to take medications (p = 0.01).
Inclusion of drugs with better safety profiles and improved access to care could
further enhance outcomes.
PMID- 26443265
TI - Developing an intervention to facilitate family communication about inherited
genetic conditions, and training genetic counsellors in its delivery.
AB - Many families experience difficulty in talking about an inherited genetic
condition that affects one or more of them. There have now been a number of
studies identifying the issues in detail, however few have developed
interventions to assist families. The SPRinG collaborative have used the UK
Medical Research Council's guidance on Developing and Evaluating Complex
Interventions, to work with families and genetic counsellors (GCs) to co-design a
psycho-educational intervention to facilitate family communication and promote
better coping and adaptation to living with an inherited genetic condition for
parents and their children (<18 years). The intervention is modelled on multi
family discussion groups (MFDGs) used in psychiatric settings. The MFDG was
developed and tested over three phases. First focus groups with parents, young
people, children and health professionals discussed whether MFDG was acceptable
and proposed a suitable design. Using evidence and focus group data, the
intervention and a training manual were developed and three GCs were trained in
its delivery. Finally, a prototype MFDG was led by a family therapist and co
facilitated by the three GCs. Data analysis showed that families attending the
focus groups and intervention thought MFDG highly beneficial, and the pilot
sessions had a significant impact on their family' functioning. We also
demonstrated that it is possible to train GCs to deliver the MFDG intervention.
Further studies are now required to test the feasibility of undertaking a
definitive randomised controlled trial to evaluate its effectiveness in improving
family outcomes before implementing into genetic counselling practice.
PMID- 26443266
TI - A recessive form of extreme macrocephaly and mild intellectual disability
complements the spectrum of PTEN hamartoma tumour syndrome.
AB - PTEN hamartoma tumour syndrome (PHTS) is caused by heterozygous variants in PTEN
and is characterised by tumour predisposition, macrocephaly, and cognition
impairment. Bi-allelic loss of PTEN activity has not been reported so far and
animal models suggest that bi-allelic loss of PTEN activity is embryonically
lethal. Here, we report the identification of a novel homozygous variant in PTEN,
NM_000314.4; c.545T>C; p.Leu182Ser, in two adolescent siblings with severe
macrocephaly and mild intellectual disability. The variant is predicted to be
damaging and is associated with significantly increased phospho-S6 downstream of
PTEN. The absence of tumours in the two homozygous siblings as well as lack of
symptoms of PHTS in the heterozygous carriers of the family suggest that this
particular variant is functionally hypomorphic rather than deleterious.
PMID- 26443269
TI - Clinical utility gene card for: acrodermatitis enteropathica - update 2015.
PMID- 26443268
TI - CUGC for hereditary fibrosing poikiloderma with tendon contractures, myopathy,
and pulmonary fibrosis (POIKTMP).
PMID- 26443267
TI - Imbalance of excitatory/inhibitory synaptic protein expression in iPSC-derived
neurons from FOXG1(+/-) patients and in foxg1(+/-) mice.
AB - Rett syndrome (RTT) is a severe neurodevelopmental disorder associated with
mutations in either MECP2, CDKL5 or FOXG1. The precise molecular mechanisms that
lead to the pathogenesis of RTT have yet to be elucidated. We recently reported
that expression of GluD1 (orphan glutamate receptor delta-1 subunit) is increased
in iPSC-derived neurons obtained from patients with mutations in either MECP2 or
CDKL5. GluD1 controls synaptic differentiation and shifts the balance between
excitatory and inhibitory synapses toward the latter. Thus, an increase in GluD1
might be a critical factor in the etiology of RTT by affecting the
excitatory/inhibitory balance in the developing brain. To test this hypothesis,
we generated iPSC-derived neurons from FOXG1(+/-) patients. We analyzed mRNA and
protein levels of GluD1 together with key markers of excitatory and inhibitory
synapses in these iPSC-derived neurons and in Foxg1(+/-) mouse fetal (E11.5) and
adult (P70) brains. We found strong correlation between iPSC-derived neurons and
fetal mouse brains, where GluD1 and inhibitory synaptic markers (GAD67 and GABA
AR-alpha1) were increased, whereas the levels of a number of excitatory synaptic
markers (VGLUT1, GluA1, GluN1 and PSD-95) were decreased. In adult mice, GluD1
was decreased along with all GABAergic and glutamatergic markers. Our findings
further the understanding of the etiology of RTT by introducing a new
pathological event occurring in the brain of FOXG1(+/-) patients during embryonic
development and its time-dependent shift toward a general decrease in brain
synapses.
PMID- 26443271
TI - The ulnar artery pseudoaneurysm.
PMID- 26443270
TI - Schisandrae Fructus Inhibits IL-1beta-Induced Matrix Metalloproteinases and
Inflammatory Mediators Production in SW1353 Human Chondrocytes by Suppressing NF
kappaB and MAPK Activation.
AB - Proinflammatory cytokine interleukin-1 beta (IL-1beta) plays a crucial role in
the pathogenesis of osteoarthritis (OA) by stimulating several mediators that
contribute to cartilage degradation. Schisandrae Fructus (SF), the dried fruit of
Schisandra chinensis (Turcz.) Baill. (Magnoliaceae), is widely used in
traditional medicine for the treatment of a number of chronic inflammatory
diseases. This study investigated the antiosteoarthritis properties of an ethanol
extract of SF on IL-1beta-stimulated SW1353 chondrocytes. SF attenuated IL-1beta
induced expression and activity of matrix metalloproteinase (MMP)-1, MMP-3, and
MMP-13 and also reduced the elevated levels of cyclooxygenase-2 and inducible
nitric oxide synthase associated with the inhibition of prostaglandin E2 and
nitric oxide production in IL-1beta-stimulated SW1353 chondrocytes. In addition,
SF markedly suppressed the nuclear translocation of nuclear factor-kappa B (NF
kappaB) by blocking inhibitor kappaB-alpha degradation and inhibited the
phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated
protein kinase (MAPK). These results indicate that the inhibitory effect of SF on
IL-1beta-stimulated expression of MMPs and inflammatory mediators production in
SW1353 cells were associated with the suppression of the NF-kappaB and JNK/p38
MAPK signaling pathways. The results from this study indicate that SF may have
therapeutic potential for the treatment of OA due to its anti-inflammatory and
chondroprotective features.
PMID- 26443272
TI - Skeletal stability of surgery-first bimaxillary orthognathic surgery for skeletal
class III malocclusion, using standardized criteria.
AB - The purpose of this study was to compare the postoperative stability following
bimaxillary surgery performed either with or without preoperative orthodontic
treatment, in class III malocclusion patients. These patients were enrolled using
standardized inclusion criteria. Forty patients with a class III malocclusion
were included in this retrospective study. Inclusion criteria were class III
malocclusion with and without premolar extraction, <3mm midline deviation, and
<5mm arch width discordance. Patients were assigned to the conventional
bimaxillary surgery group (n=20) or the surgery-first bimaxillary surgery group
(n=20). Serial cephalometric radiographs obtained before surgery (T0), at 2
months after surgery (T1), and at 6 months after surgery (T2) were used to assess
the variation in surgical change (T0 to T1) and postsurgical change (T1 to T2).
Eight linear and three angular parameters were used to evaluate postoperative
stability. With respect to postsurgical changes, significant differences were
observed in the changes for the vertical reference plane to the posterior nasal
spine, horizontal reference plane to B-point, and occlusal plane angle in both
groups. No statistically significant differences in the relapse rates were
observed between the two groups. No significant differences were observed between
the two groups in terms of the postoperative stability.
PMID- 26443273
TI - Palatal bone dimensions on cone beam computed tomography. Implications for the
palate as autogenous donor site: an observational study.
AB - This study analyzed cone beam computed tomography (CBCT) records. Radiographic
image analysis included: (1) the width and height of the palatal vault, and
diameter and location of the incisive foramen; (2) the potential block graft
dimensions and their correlation to arch dimensions; (3) the potential graft size
and its variation by sex. CBCT scans of 76 patients were included, 42 from female
patients and 34 from male patients (mean age 42.3 years). The mean palatal width
was 35.2+/-3.4 mm, while the mean palatal height was 15.2+/-2.9 mm. The mean
diameter of the incisive foramen was 3.1+/-1.3. mm. The mean potential osteotomy
diameter was 7.8+/-1.5 mm. The mean osteotomy length varied according to site:
central incisor region, 5.9+/-2.0 mm; lateral incisor region, 5.2+/-2.1 mm;
canine region, 4.7+/-1.9 mm; premolar region, 4.1+/-1.7 mm. A positive
correlation was observed between the osteotomy diameter and the palatal width: a
greater osteotomy length was obtained from the more anterior teeth position.
Males presented significantly greater osteotomy diameter and length compared to
females. The palate represents a potential site for the harvest of autogenous
bone block grafts for the reconstruction of ridge defects.
PMID- 26443274
TI - Neonatal care in low- and middle-income countries. Introduction.
PMID- 26443275
TI - Thinking beyond global neonatal mortality rates.
PMID- 26443278
TI - Social relationships and social support among post-war youth in Northern Uganda.
AB - Although social relationships and social support are salient factors for post-war
adolescents' psychosocial coping and adjustment, there is only limited
information regarding war-affected adolescents' views on social support and the
relationships within which social support is provided. This study therefore
explored both elements among a clinical sample of 20 adolescents living in post
war Northern Uganda. Following Braun and Clarke's thematic analysis, we found a
prominent role of the biological mother and other primary biological family
members in the upbringing of our participants. Spiritual and material support
were perceived to be the most important type of support, respectively, while the
adolescents were growing up and in their current lives. These findings provide
support for the perception that caregiving systems are adaptable to particular
sociocultural contexts. Further, the importance of particular functions of social
support could signify a potentially selective buffering effect of these functions
in adverse contexts. Because of the importance of the primary biological family
and the salient role of parent-child relationships in the face of adversity,
future research needs to focus on this particular kind of social relationship in
contexts of prolonged collective violence.
PMID- 26443277
TI - Structural basis of Ornithine Decarboxylase inactivation and accelerated
degradation by polyamine sensor Antizyme1.
AB - Ornithine decarboxylase (ODC) catalyzes the first and rate-limiting step of
polyamine biosynthesis in humans. Polyamines are essential for cell proliferation
and are implicated in cellular processes, ranging from DNA replication to
apoptosis. Excessive accumulation of polyamines has a cytotoxic effect on cells
and elevated level of ODC activity is associated with cancer development. To
maintain normal cellular proliferation, regulation of polyamine synthesis is
imposed by Antizyme1 (AZ1). The expression of AZ1 is induced by a ribosomal
frameshifting mechanism in response to increased intracellular polyamines. AZ1
regulates polyamine homeostasis by inactivating ODC activity and enhancing its
degradation. Here, we report the structure of human ODC in complex with N
terminally truncated AZ1 (cAZ1). The structure shows cAZ1 binding to ODC, which
occludes the binding of a second molecule of ODC to form the active homodimer.
Consequently, the substrate binding site is disrupted and ODC is inactivated.
Structural comparison shows that the binding of cAZ1 to ODC causes a global
conformational change of ODC and renders its C-terminal region flexible,
therefore exposing this region for degradation by the 26S proteasome. Our
structure provides the molecular basis for the inactivation of ODC by AZ1 and
sheds light on how AZ1 promotes its degradation.
PMID- 26443279
TI - Response evaluation in mesothelioma: Beyond RECIST.
AB - Malignant pleural mesothelioma (MPM) typically demonstrates a non-spherical
growth pattern, so it is often difficult to accurately categorize change in
tumour burden using size-based tumour response criteria (e.g., WHO (World Health
Organisation), RECIST (Response Evaluation Criteria in Solid Tumours) and
modified RECIST). Functional imaging techniques are applied to derive
quantitative measurements of tumours, which reflect particular aspects of the
tumour pathophysiology. By quantifying how these measurements change with
treatment, it is possible to observe treatment effects. In this review, we survey
the existing roles of CT and MRI for the management of MPM, including the
currently applied size measurement criteria for the assessment of treatment
response. New functional imaging techniques, such as positron emission tomography
(PET), diffusion-weighted MRI (DWI) and dynamic contrast-enhanced MRI (DCE-MRI)
that may potentially improve the assessment of treatment response will be
highlighted and discussed.
PMID- 26443280
TI - Cerebellar ataxia with unilateral high frequency vestibulopathy and caloric
disinhibition.
PMID- 26443281
TI - Continuous duodenal levodopa infusion in a patient with Crohn's disease and small
bowel surgery - Case report.
PMID- 26443283
TI - Our journal: past, present and future.
PMID- 26443282
TI - Differential regulation of matrix metalloproteinases in varicella zoster virus
infected human brain vascular adventitial fibroblasts.
AB - Upon reactivation, varicella zoster virus (VZV) spreads transaxonally, infects
cerebral arteries and causes ischemic or hemorrhagic stroke, as well as
aneurysms. The mechanism(s) of VZV-induced aneurysm formation is unknown.
However, matrix metalloproteinases (MMPs), which digest extracellular structural
proteins in the artery wall, play a role in cerebral and aortic artery aneurysm
formation and rupture. Here, we examined the effect of VZV infection on
expression of MMP-1, -2, -3, and -9 in primary human brain vascular adventitial
fibroblasts (BRAFS). At 6 days post-infection, VZV- and mock-infected BRAFs were
analyzed for mRNA levels of MMP-1, -2, -3 and -9 by RT-PCR and for corresponding
total intra- and extracellular protein levels by multiplex ELISA. The activity of
MMP-1 was also measured in a substrate cleavage assay. Compared to mock-infected
BRAFs, MMP-1, MMP-3 and MMP-9 transcripts, cell lysate protein and conditioned
supernatant protein were all increased in VZV-infected BRAFs, whereas MMP-2
transcripts, cell lysate protein and conditioned supernatant protein were
decreased. MMP-1 from the conditioned supernatant of VZV-infected BRAFs showed
increased cleavage activity on an MMP-1-specific substrate compared to mock
infected BRAFs. Differential regulation of MMPs in VZV-infected BRAFs may
contribute to aneurysm formation in VZV vasculopathy.
PMID- 26443284
TI - Diabetes and driving: 2015 Canadian Diabetes Association updated recommendations
for private and commercial drivers.
PMID- 26443285
TI - The Canadian Diabetes Association names Dr. Barry I. Posner as the 2015 Clinical
& Scientific Section Lifetime Achievement Award Recipient.
PMID- 26443286
TI - SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): revised
publication guidelines from a detailed consensus process.
AB - Since the publication of Standards for Quality Improvement Reporting Excellence
(SQUIRE 1.0) guidelines in 2008, the science of the field has advanced
considerably. In this manuscript, we describe the development of SQUIRE 2.0 and
its key components. We undertook the revision between 2012 and 2015 using 1)
semistructured interviews and focus groups to evaluate SQUIRE 1.0 plus feedback
from an international steering group; 2) 2 face-to-face consensus meetings to
develop interim drafts and 3) pilot testing with authors and a public comment
period. SQUIRE 2.0 emphasizes the reporting of 3 key components of systematic
efforts to improve the quality, value and safety of healthcare: the use of formal
and informal theory in planning, implementing and evaluating improvement work;
the context in which the work is done and the study of the intervention(s).
SQUIRE 2.0 is intended for reporting the range of methods used to improve
healthcare, recognizing that they can be complex and multidimensional. It
provides common ground to share these discoveries in the scholarly literature
(www.squire-statement.org).
PMID- 26443287
TI - Addendum to policies, guidelines and consensus statements: pharmacologic
management of type 2 diabetes: 2015 interim update.
PMID- 26443288
TI - Assessment of clonality and serotypes of Streptococcus mutans among children by
multilocus sequence typing.
AB - Studies using multilocus sequence typing (MLST) have demonstrated that
Streptococcus mutans isolates are genetically diverse. Our laboratory previously
demonstrated clonality of S. mutans using MLST but could not discount the
possibility of sampling bias. In this study, the clonality of randomly selected
S. mutans plaque isolates from African-American children was examined using MLST.
Serotype and the presence of collagen-binding proteins (CBPs) encoded by cnm/cbm
were also assessed. One-hundred S. mutans isolates were randomly selected for
MLST analysis. Sequence analysis was performed and phylogenetic trees were
generated using start2 and mega. Thirty-four sequence types were identified, of
which 27 were unique to this population. Seventy-five per cent of the isolates
clustered into 16 clonal groups. The serotypes observed were c (n = 84), e (n =
3), and k (n = 11). The prevalence of S. mutans isolates of serotype k was
notably high, at 17.5%. All isolates were cnm/cbm negative. The clonality of S.
mutans demonstrated in this study illustrates the importance of localized
population studies and are consistent with transmission. The prevalence of
serotype k, a recently proposed systemic pathogen, observed in this study, is
higher than reported in most populations and is the first report of S. mutans
serotype k in a United States population.
PMID- 26443289
TI - Young Coconut Juice Supplementation Results in Greater Bone Mass and Bone
Formation Indices in Ovariectomized Rats: A Preliminary Study.
AB - Young coconut juice (Cocos nucifera Linn.) (YCJ) has traditionally been consumed
to alleviate symptoms associated with menopause by women in Southeast Asia. The
aim of the present study was to determine the effects of YCJ on bone metabolism
in ovariectomized rats. Female 10-week-old Wistar rats were randomly assigned to
the following 4 groups: Baseline, Sham, Ovx, and Ovx + YCJ (n = 10 rats per
group). Rats in the Baseline group were sacrificed immediately, and those in the
other groups were subjected to either sham operation (Sham) or bilateral
ovariectomy (Ovx and Ovx + YCJ). The Ovx + YCJ rats were administered 5*
concentrated YCJ at a dose of 10 mL/kg body weight per day. Six weeks after
surgery, the rats were sacrificed, and indices of bone mass and bone
histomorphometry were measured. The bone mineral density of the left femur was
significantly higher in the Ovx + YCJ group compared with the Ovx group. In
addition, the Ovx + YCJ group showed significantly higher measurements for bone
formation rate compared with the Ovx group. These findings suggest that YCJ
supplementation has a positive effect on bone metabolism and thus represents a
possible intervention to slow the bone loss observed following menopause.
PMID- 26443290
TI - IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated
Using Continuous Glucose Monitoring and a Standardized Meal Test.
AB - OBJECTIVE: IDegLira is a novel, fixed-ratio combination of the long-acting basal
insulin, insulin degludec, and the long-acting glucagon-like peptide-1 analog
liraglutide. We studied the effect of IDegLira versus its components on
postprandial glucose (PPG) in type 2 diabetes. METHODS: In this substudy, 260
(15.6%) of the original 1663 patients with inadequate glycemic control
participating in a 26-week, open-label trial (DUAL I) were randomized 2:1:1 to
once-daily IDegLira, insulin degludec or liraglutide. Continuous glucose
monitoring (CGM) for 72 hours and a meal test were performed. RESULTS: At week
26, IDegLira produced a significantly greater decrease from baseline in mean PPG
increment (normalized iAUC0-4h) than insulin degludec (estimated treatment
difference [ETD] -12.79 mg/dl [95% CI: -21.08; -4.68], P = .0023) and a similar
magnitude of decrease as liraglutide (ETD -1.62 mg/dl [95% CI: -10.09; 6.67], P =
.70). CGM indicated a greater reduction in change from baseline in PPG increment
(iAUC0-4h) for IDegLira versus insulin degludec over all 3 main meals (ETD -6.13
mg/dl [95% CI: -10.27, -1.98], P = .0047) and similar reductions versus
liraglutide (ETD -1.80 mg/dl [95% CI: -2.52, 5.95], P = .4122). Insulin secretion
ratio and static index were greater for IDegLira versus insulin degludec (P =
.048 and P = .006, respectively) and similar to liraglutide (P = .45 and P =
.895, respectively). CONCLUSIONS: Once-daily IDegLira provides significantly
better PPG control following a mixed meal test than insulin degludec. The
improvement is at least partially explained by higher endogenous insulin
secretion and improved beta cell function with IDegLira. The benefits of
liraglutide on PPG control are maintained across all main meals in the
combination.
PMID- 26443291
TI - Classification of Physical Activity: Information to Artificial Pancreas Control
Systems in Real Time.
AB - Physical activity has a wide range of effects on glucose concentrations in type 1
diabetes (T1D) depending on the type (ie, aerobic, anaerobic, mixed) and duration
of activity performed. This variability in glucose responses to physical activity
makes the development of artificial pancreas (AP) systems challenging. Automatic
detection of exercise type and intensity, and its classification as aerobic or
anaerobic would provide valuable information to AP control algorithms. This can
be achieved by using a multivariable AP approach where biometric variables are
measured and reported to the AP at high frequency. We developed a classification
system that identifies, in real time, the exercise intensity and its reliance on
aerobic or anaerobic metabolism and tested this approach using clinical data
collected from 5 persons with T1D and 3 individuals without T1D in a controlled
laboratory setting using a variety of common types of physical activity. The
classifier had an average sensitivity of 98.7% for physiological data collected
over a range of exercise modalities and intensities in these subjects. The
classifier will be added as a new module to the integrated multivariable adaptive
AP system to enable the detection of aerobic and anaerobic exercise for enhancing
the accuracy of insulin infusion strategies during and after exercise.
PMID- 26443292
TI - Cost Burden of Chronic Pain Patients in a Large Integrated Delivery System in the
United States.
AB - OBJECTIVES: To estimate all-cause healthcare resource utilization and costs among
chronic pain patients within an integrated healthcare delivery system in the
United States. METHODS: Electronic medical records and health claims data from
the Henry Ford Health System were used to determine healthcare resource
utilization and costs for patients with 24 chronic pain conditions. Patients were
identified by >= 2 ICD-9-CM codes >= 30 days apart from January to December,
2010; the first ICD-9 code was the index event. Continuous coverage for 12 months
pre- and postindex was required. All-cause direct medical costs were determined
from billing data. RESULTS: A total of 12,165 patients were identified for the
analysis. After pharmacy, the most used resource was outpatient visits, with a
mean of 18.8 (SD 13.2) visits per patient for the postindex period; specialty
visits accounted for 59.0% of outpatient visits. Imaging was utilized with a mean
of 5.2 (SD 5.5) discrete tests per patient, and opioids were the most commonly
prescribed medication (38.7%). Annual direct total costs for all conditions were
$386 million ($31,692 per patient; a 40% increase from the pre-index). Pharmacy
costs comprised 14.3% of total costs, and outpatient visits were the primary cost
driver. CONCLUSIONS: Chronic pain conditions impose a substantial burden on the
healthcare system, with musculoskeletal conditions associated with the highest
overall costs. Costs appeared to be primarily related to use of outpatient
services. This type of research supports integrated delivery systems as a source
for assessing opportunities to improve patient outcomes and lower the costs for
chronic pain patients.
PMID- 26443293
TI - An observational study of the 'isolated forearm technique' in unparalysed,
spontaneously breathing patients.
AB - The isolated forearm technique enables a patient, otherwise paralysed by
neuromuscular blockade, to communicate by movement if wakeful during surgery. The
positive response rate to verbal command is high (~32%). The 5th National Audit
Project recommended that this monitoring technique should become more widely
taught and considered, so this study was designed to assess its utility as a
standard of care in unparalysed patients. A positive response rate as high as in
the paralysed would justify local adoption. Therefore, 100 consecutive patients
undergoing urology surgery were given verbal commands to move at two-minute
intervals from induction of anaesthesia (fentanyl and propofol) to full emergence
and extubation of the supraglottic airway. Anaesthesia was maintained with
isoflurane in oxygen/nitrous oxide. Although 24 patients moved during surgery
(and therefore needed additional anaesthetic), none moved to verbal command. Even
at extubation, when patients moved to expel the airway, there was no response to
command until after wakening. These results suggest that in contrast to its use
in paralysed patients, the isolated forearm technique does not yield useful
information about the patient's state of wakefulness in the unparalysed. Another
interpretation is that unparalysed patients are less prone to wakefulness than
the paralysed.
PMID- 26443294
TI - Clustering medication adherence behavior based on beliefs in medicines and
illness perceptions in patients taking asthma maintenance medications.
AB - OBJECTIVES: The prevalence of medication non-adherence is 50% in chronic disease
conditions and varies from 30% to 70% in asthma maintenance medications. A major
drawback in addressing medication non-adherence is the short time available for
patient consultations, which limits the ability of the clinician in identifying
the problem. Thus, this study explores how medication adherence behavior can be
clustered and identifies the unique characteristics of each cluster so that
clinicians can recognize the cluster characteristics in patients to provide
targeted interventions. The study objectives were to: (1) cluster patients'
medication adherence behavior with asthma maintenance medications based on their
beliefs in medicines and illness perceptions, and (2) describe the
characteristics of the patients in each cluster based on psychosocial, clinical,
and demographic characteristics. RESEARCH DESIGN AND METHODS: A cross-sectional
online survey design on a convenience sample of adult individuals who were taking
asthma maintenance medications. MAIN OUTCOME MEASURES: Self-reported medication
adherence using Morisky scale, beliefs in medicines using Beliefs in Medicines
Questionnaire, and illness perceptions using the Brief Illness Perceptions
Questionnaire. RESULTS: The cluster analysis with 392 subjects resulted in five
clusters based on patients' beliefs in medicines and their illness perceptions.
The clusters formed had distinct characteristics that lend themselves to
monitoring or for which targeted interventions can be framed to improve
medication adherence. LIMITATIONS: The study only examined asthma maintenance
medications limiting the generalizability of the study. Also, all the data
collected including medication adherence were self-reported data from an online
panel. This can cause selection bias and lack of generalizability. CONCLUSIONS:
The study demonstrated how the concept of 'non-adherence' is different for
different patients and the need for tailored interventions for each type of non
adherence. With the limited consultation time available for clinicians to
communicate with the patients, identifying the characteristics of patients in
different clusters can assist clinicians in providing appropriate targeted
interventions.
PMID- 26443295
TI - Substance use, sexual behaviour and prevention strategies of Vancouver gay and
bisexual men who recently attended group sex events.
AB - Group sex events are an epidemiologically important part of some gay and bisexual
men's sexual culture in Canada. Associated with condomless anal intercourse and
polysubstance use, such events have been cited as disproportionally contributing
to HIV infection rates. We analysed questionnaire data from the Momentum Health
Study in Vancouver, Canada, to understand substance use, sexual behaviour,
psychosocial variables (Sexual Sensation Seeking, Sexual Escape Motivation,
Treatment Optimism) and HIV prevention strategies (sero-sorting, strategic
positioning, avoiding anal sex, disclosure, treatment as prevention) of men
attending such events, which were defined as group (n >= 4 partners) sex parties,
blackout events and darkrooms. Analysis by multivariable logistic regression
compared men attending group sex events within the past six months (n = 180) with
non-attendees (n = 539). Results showed that attendees reported: (1)
significantly higher use of sex drugs and alcohol consumption, (2) higher scores
on the Sexual Sensation Scale, more anal sex partners, greater odds of any
condomless anal sex with sero-discordant partners and greater odds of reporting
fisting and sex toy use and (3) different prevention practices that varied by HIV
serostatus. Findings are interpreted in light of the importance of pleasure,
sociality and HIV/STI prevention strategies associated with group sex events.
Findings contribute to the development of appropriate education and intervention
for attendees.
PMID- 26443296
TI - Spiritual well-being and quality of life among Icelanders receiving palliative
care: data from Icelandic pilot-testing of a provisional measure of spiritual
well-being from the European Organisation for Research and Treatment of Cancer.
AB - Palliative care focuses on improving quality of life (QoL). This study examined
the feasibility of the Icelandic version of a provisional European Organisation
for Research and Treatment of Cancer (EORTC) measure of spiritual well-being
(SWB), and explored the relationship between SWB and QoL for palliative care
patients in Iceland. Instruments from the EORTC were used: the provisional
measure of SWB, which was undergoing pilot-testing in Iceland, and the EORTC QLQ
C15-PAL. The correlation between scores was examined and descriptive statistics
were used. Structured interviews explored feasibility. Thirty persons
participated with average age 72 years. Belief in God or a higher power had the
mean 3.33 on a 1-4 scale and the mean for overall SWB was 5.73 on a 1-7 scale.
The mean score for global health/QoL was 59.4, physical functioning 48.5 and
emotional functioning 78.9 on a 0-100 scale. Overall QoL was positively
correlated with SWB showing r(30) = 0.386, P = 0.035. The participants found that
answering the provisional EORTC QLQ-SWB prompted an emotional response and took
the opportunity to discuss the subject. The provisional SWB measure was found
relevant for the Icelandic context, and the study indicates that SWB and QoL are
closely connected.
PMID- 26443297
TI - Mechanical thrombectomy with 'ADAPT' technique by transcervical access in acute
ischemic stroke.
AB - BACKGROUND: The mechanical thrombectomy (MT) for endovascular clot retrieval has
dramatically improved successful revascularization and clinical outcome in
selected acute stroke patients. MT is typically performed via a transfemoral
approach, but catheterization of the occluded vessel can be problematic in cases
of extensive vessel tortuosity. We describe a case of MT with the 'ADAPT'
technique by direct carotid access due to an inability to catheterize the ICA by
a transfemoral approach for acute cerebral ischemia in the setting of left MCA
occlusion. Excellent angiographic and good clinical results were obtained without
any complications. CASE REPORT: An 80-year-old woman was admitted with a stroke
by occlusion of the left MCA, with an NIHSS: 11, and an ASPECT: 7 in the CT.
Under sedation a transfemoral angiography was performed, but after multiple
attempts, it was impossible to make a stable catheterization of the left CCA. A
transcervical approach was pursued. With ultrasound guidance the CCA was
catheterized. Using the 'ADAPT' technique, we performed a successful MT. Post
procedure angiography (at 14 minutes) demonstrated recanalization of the entire
left MCA (TICI: 3), without complications. The carotid access point was closed
with a percutaneous closure. Control TC at 24 h showed a slight hypodensity in
the left lenticular nucleus, and loss of gray-white matter differentiation in the
adjacent cortex. Neurologically, the patient presented with progressive
improvement. At discharge, she had an NIHSS: 0, mRS: 0 and Barthel: 100.
CONCLUSIONS: MT by direct carotid access is an effective alternative technique in
those cases where it is not accessible by a transfemoral approach.
PMID- 26443298
TI - Functional MRI in clinical practice: Assessment of language and motor for pre
surgical planning.
AB - Functional magnetic resonance imaging (fMRI) has been widely used for pre
neurosurgical planning and may eventually become a routine pre-surgical imaging
modality. The validity of fMRI for clinical application depends on various
factors such as proper task selection, correct statistical analysis and threshold
setting with appropriate patient cooperation. This study was performed on 40
patients with different types of brain mass lesions or hippocampal sclerosis to
assess the role of appropriate patient selection for achieving a reliable fMRI
result. Accurate and reproducible fMRI strongly depends on the patient's
cooperation. In this study we observed that a pre-test mock fMRI session held by
a radiologist may help to predict which patients are more or less suitable
candidates for fMRI.
PMID- 26443299
TI - Absent circle of Willis with vascular pollarding in an adult with colpocephaly: A
developmental perspective.
AB - Absent circle of Willis (COW) has been described in cases of severe forms of
cerebral developmental anomalies such as alobar prosencephaly. However, there are
no reports of absent COW in patients with a milder form of cerebral abnormality
such as colpocephaly. We report a unique case of an adult with colpocephaly and
absent COW and discuss their association from a developmental perspective.
PMID- 26443300
TI - Extracranial, peritoneal seeding of primary malignant brain tumors through
ventriculo-peritoneal shunts in children: Case report and review of the
literature.
AB - INTRODUCTION: Ventriculoperitoneal shunts (VPS) have been implicated as a source
of the extraneural spread of a wide variety of central nervous system tumors. The
purpose is to review the literature on peritoneal seeding of central nervous
system tumors from VPS in the context of a case report. METHODS: Medline was
searched using the phrase 'peritoneal seeding ventriculoperitoneal shunt'.
Inclusion criteria included patients (<18 years) with evidence of peritoneal
seeding from VPS. RESULTS: Search of the literature revealed a final total of 22
articles and a total of 28 patients. CASE REPORT: A 7-year-old boy presented with
intermittent vomiting, headaches, photophobia; a 4.4 cm left thalamic mass
(glioblastoma multiforme) was found. Occipital VPS catheters were placed for
increasing hydrocephalus and the patient developed increased abdominal distention
and pain. Computed tomography revealed diffuse ascites with carcinomatosis and
the patient was diagnosed clinically with peritoneal metastases. DISCUSSION: Our
case report and literature review revealed 28 cases of central nervous system
tumors demonstrating evidence of extraneural spread associated with VPS in
children in a wide variety of tumors. Larger studies are required to evaluate VPS
as potential risk factors for peritoneal seeding and familiarity with potential
VPS-related peritoneal seeding is important for diagnostic consideration.
PMID- 26443301
TI - Novel brain MRI abnormalities in Gitelman syndrome.
AB - Gitelman syndrome is an autosomal recessive renal tubular disorder characterized
by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. The
syndrome is caused by a defective thiazide-sensitive sodium chloride co
transporter in the distal convoluted tubules of the kidneys. Gitelman syndrome
could be confused with Bartter syndrome; the main differentiating feature is the
presence of low urinary calcium excretion in the former. Descriptions of
neuroradiological imaging findings associated with Gitelman syndrome are very
scarce in the literature and include basal ganglia calcification, idiopathic
intracranial hypertension and sclerochoroidal calcification. Cauda equina
syndrome-like presentation has been reported, but without any corresponding
imaging findings on lumbar spine MRI. We report a 13-year-old male with Gitelman
syndrome who presented with altered mental status following a fall and scalp
laceration and unremarkable brain CT, followed during hospitalization by
somnolence and seizures. Metabolically the patient demonstrated hypokalemia and
hypomagnesemia. MRI demonstrated features of encephalopathy including
predominantly right-sided cerebral hemispheric signal abnormality and cytotoxic
edema, with bilateral symmetric involvement of the thalami, midbrain tegmentum
and tectum and cerebellar dentate nuclei. MRI after five months obtained during a
later episode of encephalopathy showed resolution of the signal abnormalities
with setting in of brain atrophy and also areas of newly developed cytotoxic
edema in the left thalamus, bilateral dorsal midbrain and right greater than left
dentate nuclei. The described abnormalities, either recurrent or in isolation,
have not previously been published in patients with Gitelman syndrome. We believe
that the findings are due to alteration of respiratory chain function secondary
to the metabolic derangement and hence have a similar imaging appearance as
encephalopathy related to mitochondrial cytopathy or metabolic encephalopathy.
PMID- 26443303
TI - Experimental and theoretical investigations of four 3d-4f butterfly single
molecule magnets.
AB - The syntheses, structures, and characterization of four 3d-4f butterfly clusters
are described. With different polyhydroxy Schiff-base ligands 2-(((2-hydroxy-3
methoxyphenyl)methylene)amino)-2-(hydroxymethyl)-1,3-propanediol (H4L1) and 2
(2,3-dihydroxpropyliminomethyl)-6-methoxyphenol (H3L2), three heterotetranuclear
NiLn complexes (NiDy-L1 (1), NiTb-L2 (2), NiDy-L2 (3)) and one heterohexanuclear
CoDy complex (4) were obtained. The three heterotetranuclear NiLn complexes
display a central planar butterfly topology. The heterohexanuclear complex was
built from butterfly CoDy clusters and two Dy(III) ions by the bridging of
pivalate. The vertices of the body positions of the butterfly are occupied by
transition metal ions in all four complexes. Magnetic analyses indicate that the
complexes exhibit typical single-molecule magnet behaviour with anisotropy
barriers of 33.7 cm(-1), 60.3 cm(-1), 39.6 cm(-1), and 18.4 cm(-1) for 1-4,
respectively. Ab initio calculations were performed on these complexes, and the
low lying electronic structure of each Ln(III) (Ln = Dy, Tb) ion and the magnetic
interactions were determined. It was found that the two Ln ions may have much
more contribution to the total relaxation barrier through the stronger 3d-4f
exchange couplings compared to weak Ln-Ln interactions.
PMID- 26443302
TI - Microbial metabolic networks in a complex electrogenic biofilm recovered from a
stimulus-induced metatranscriptomics approach.
AB - Microorganisms almost always exist as mixed communities in nature. While the
significance of microbial community activities is well appreciated, a thorough
understanding about how microbial communities respond to environmental
perturbations has not yet been achieved. Here we have used a combination of
metagenomic, genome binning, and stimulus-induced metatranscriptomic approaches
to estimate the metabolic network and stimuli-induced metabolic switches existing
in a complex microbial biofilm that was producing electrical current via
extracellular electron transfer (EET) to a solid electrode surface. Two stimuli
were employed: to increase EET and to stop EET. An analysis of cell activity
marker genes after stimuli exposure revealed that only two strains within eleven
binned genomes had strong transcriptional responses to increased EET rates, with
one responding positively and the other responding negatively. Potential
metabolic switches between eleven dominant members were mainly observed for
acetate, hydrogen, and ethanol metabolisms. These results have enabled the
estimation of a multi-species metabolic network and the associated short-term
responses to EET stimuli that induce changes to metabolic flow and cooperative or
competitive microbial interactions. This systematic meta-omics approach
represents a next step towards understanding complex microbial roles within a
community and how community members respond to specific environmental stimuli.
PMID- 26443304
TI - A homozygous PAX3 mutation leading to severe presentation of Waardenburg syndrome
with a prenatal diagnosis.
PMID- 26443305
TI - Clinical features of rheumatoid arthritis-associated interstitial lung disease.
AB - Interstitial lung disease (ILD) is the most common extra-articular manifestations
of rheumatoid arthritis (RA) in the lung. This study aimed to identify clinical
features of RA-associated ILD (RA-ILD). Patients with RA were retrospectively
enrolled and sub-classified as RA-ILD or RA without ILD based on high-resolution
computed tomography imaging. Pulmonary function testing parameters and levels of
RA-related biomarkers, tumour markers, and acute-phase proteins were compared
between the two groups. Logistic regression model was used to assess the strength
of association between RA-ILD and clinical features of interest. Receiver
operating characteristic analysis was performed to assess potential predictive
value of clinical features for detecting RA-ILD. Comparison analysis indicated
that the percentage of predicted value of total lung capacity, inspiratory
capacity, and diffusion capacity of the lung for carbon monoxide (DLCO) were
reduced in patients with RA-ILD. Tumour markers CA15-3 and CA125 were increased
in patients with RA-ILD. Logistic regression analysis revealed that decreased
DLCO was related to the increased likelihood of RA-ILD (OR = 0.94, 95%CI = [0.91,
0.98]). The cut-off point at 52.95 percent of predicted value could sensitively
discriminate RA patients with or without ILD. Our study suggested that DLCO value
could be a useful tool for detecting ILD in patients with RA.
PMID- 26443306
TI - Retrospective analysis of 95 patients with large vessel vasculitis: a single
center experience.
AB - AIM: Although Takayasu arteritis (TAK) and giant cell arteritis (GCA) have been
considered as distinct disease entities, similarities of these diseases have been
recently reported. However, little data is available regarding this issue in
Japanese patients with TAK and GCA. In addition, the classification criteria for
TAK established in 1990 by the American College of Rheumatology (ACR) have been
criticized due to the age restriction for disease onset (<= 40 years). Thus, we
aimed to compare the clinical characteristics of Japanese patients with TAK and
those with GCA and to clarify whether clinical differences existed between
patients with early-onset (<= 40 years) and late-onset (> 40 years) TAK. METHODS:
We enrolled 86 patients with TAK and nine with GCA who visited our department
from 1990 to 2014. The diagnoses of TAK and GCA were based on the criteria of the
Japanese Circulation Society and the ACR, respectively. RESULTS: Mean ages at
onset for TAK and GCA were 36.4 and 71.0 years, respectively. Patients with TAK
had significantly higher incidences of aortic regurgitation and carotid and
subclavian arterial involvement, lower frequencies of polymyalgia rheumatica, and
better prognoses than those with GCA. In contrast, the clinical characteristics,
distribution of arterial lesions, treatments administered, and prognoses of
patients with early- and late-onset TAK were comparable. CONCLUSIONS: These
results suggested that TAK and GCA differed substantially, and that the age
restriction (<= 40 years) may not be necessary for the diagnosis of TAK.
PMID- 26443308
TI - Intracellular Zn(2+) detection with quantum dot-based FLIM nanosensors.
AB - Fluorescence Lifetime Imaging Microscopy (FLIM) has been employed for the
detection of intracellular Zn(2+) levels, implicated in various signalling
pathways, using a family of quantum dot (QD) nanosensors. The sensing mechanism
was based on photoinduced electron transfer (PET) between an azacycle receptor
group and the QD nanoparticles.
PMID- 26443307
TI - Biosorption of alpacide blue from aqueous solution by lignocellulosic biomass:
Luffa cylindrica fibers.
AB - The aim of the present work is to develop an effective and inexpensive pollutant
removal technology using lignocellulosic fibers: Luffa cylindrica, for the
biosorption of an anionic dye: alpacide blue. The influence of some experimental
parameters such as pH, temperature, initial concentration of the polluted
solution, and mass of the sorbent L. cylindrica on the biosorption of alpacide
blue by L. cylindrica fibers has been investigated. Optimal parameters for
maximum quantity of biosorption dye were achieved after 2 h of treatment in a
batch system using an initial dye concentration of 20 mg/L, a mass of 1 g of L.
cylindrica fibers, and pH 2. In these conditions, the quantity of dye retained is
2 mg/g and the retention rate is 78 %. Finally, a mathematical modeling of
kinetics and isotherms has been used for mathematical modeling; the model of
pseudo-second order is more appropriate to describe this phenomenon of
biosorption. Concerning biosorption isotherms, the Freundlich model is the most
appropriate for a biosorption of alpacide blue dye by L. cylindrica fibers.
PMID- 26443309
TI - Biopathology of astrocytes in human traumatic and complicated brain injuries.
Review and hypothesis.
AB - The biopathology of astrocyte cells in severe human brain traumatic injuries
complicated with subdural and epidural haematoma and hygroma is reviewed. Clear
and dense oedematous and hypertrophic reactive astrocytes are distinguished in
severe primary traumatic vasogenic and secondary cytotoxic brain oedema. Swollen
perineuronal astrocytes appear compressing and indenting clear and dark
degenerated pyramidal and non-pyramidal nerve cells, degenerated myelinated axons
and synaptic contacts. Hypertrophic astrocytes display dense cytoplasm and
contain numerous rosettes of alpha, beta- and gamma-type glycogen granules,
swollen mitochondria, dilated smooth and rough endoplasmic reticulum, oedematous
Golgi apparatus, microtubules, gliofilaments, intermediate filaments, lysosomes
and liposomes. The perisynaptic astrocyte ensheathment of synaptic contacts,
containing beta type-glycogen granules, can be traced in the neuropil,
surrounding swollen, bead-shaped dendritic profiles, and degenerated myelinated
axons. This perisynaptic glial layer is absent in severe oedematous regions. The
glycogen-rich and glycogendepleted perivascular astrocyte end-feet appear
attached or dissociated from the capillary basement membrane. Phagocytic
astrocytes can be seen engulfing degenerated synaptic contacts, necrotic
membranes, degenerated myelinated axons, and myelin ovoids. Lipofuscin-rich
astrocytes are also observed. The interastrocytary gap junctions appear either
widened, fused or fragmented. The key role of aquaporin in astrocyte swelling and
brain oedema is emphasized. The findings are compared with those reported in
experimental traumatic animal models, a large variety of pathogenetically related
neuropathological conditions, and in vivo and in vitro experimental conditions.
The contribution of pathological astrocytes to neurobehavioral disorders, such as
loss of consciousness, neurological deficits and seizures is emphasized. Some
hypotheses are postulated related to the dissociated or absent perisynaptic
layer, neurobiology of glycogen-rich and glycogen-depleted perivascular
astrocytes, the glio-basal dissociation process, abnormal astrocyte-neuronal
unit, and astrocyte participation in seizures in patients with severe and
complicated brain injuries.
PMID- 26443310
TI - Quantitative pathological changes in the cerebellum of multiple system atrophy.
AB - Multiple system atrophy (MSA) is a rare neurodegenerative disorder associated
with parkinsonism, ataxia, and autonomic dysfunction. Its pathology is primarily
subcortical comprising vacuolation, neuronal loss, gliosis, and alpha
synucleinimmunoreactive glial cytoplasmic inclusions (GCI). To quantify
cerebellar pathology in MSA, the density and spatial pattern of the pathological
changes were studied in alpha-synuclein-immunolabelled sections of the cerebellar
hemisphere in 10 MSA and 10 control cases. In MSA, densities of Purkinje cells
(PC) were decreased and vacuoles in the granule cell layer (GL) increased
compared with controls. In six MSA cases, GCI were present in cerebellar white
matter. In the molecular layer (ML) and GL of MSA, vacuoles were clustered, the
clusters exhibiting a regular distribution parallel to the edge of the folia.
Purkinje cells were randomly or regularly distributed with large gaps between
surviving cells. Densities of glial cells and surviving neurons in the ML and
surviving cells and vacuoles in the GL were negatively correlated consistent with
gliosis and vacuolation in response to neuronal loss. Principal components
analysis (PCA) suggested vacuole densities in the ML and vacuole density and cell
losses in the GL were the main source of neuropathological variation among cases.
The data suggest that: (1) cell losses and vacuolation of the GCL and loss of PC
were the most significant pathological changes in the cases studied, (2)
pathological changes were topographically distributed, and (3) cerebellar
pathology could influence cerebral function in MSA via the cerebello-dentato
thalamic tract.
PMID- 26443311
TI - Ganglion cell tumours in the sella turcica in close morphological connection with
pituitary adenomas.
AB - Ganglion cell tumours in the sellar region are uncommon. They are usually
associated with pituitary adenomas, while isolated ganglion cell neoplasms are
extremely rare. We report the clinicopathological studies of five cases diagnosed
as ganglion cell tumours located in the intrasellar region: four mixed/collision
tumours composed of gangliocytoma and pituitary adenoma, and one isolated
ganglioglioma unrelated to adenoma. Clinically, two patients presented with
acromegaly, while three others were initially diagnosed as non-functioning
adenomas. In four cases, the histopathological examination of surgical specimens
revealed intermixed lesions composed of pituitary adenoma and ganglion cell
elements. The adenomas appeared to secrete growth hormone. Electron microscopy
enabled identification of the sparsely granulated somatotroph cells. Neoplastic
neuronal lesions were composed of mature ganglion cells, including binucleate or
multinucleate cells. In all cases, boundaries between adenomatous and
gangliocytic components were not clearly demarcated, and numerous gangliocytic
cells were closely intermingled with adenomatous tissue. One case lacked
endocrine symptoms, and no pituitary adenoma was identified in the surgically
excised material; it was finally diagnosed as low-grade ganglioglioma. The
etiopathogenesis of ganglion cell neoplasms in the sellar region is not clearly
defined. Our study revealed that if ganglion cell neoplasms were combined with
adenoma, both neoplastic components were closely related to each other, and
numerous neuronal elements were strictly intermingled with adenoma cells. Such a
tissue pattern indicates that these neoplastic changes, including their common
respective etiopathogeneses, are closely related. The identification of both
components in sellar regions may have some nosological implications.
PMID- 26443312
TI - The effect of neurosphere culture conditions on the cellular metabolism of glioma
cells.
AB - Malignant gliomas, with an average survival time of 16-19 months after initial
diagnosis, account for one of the most lethal tumours overall. Current standards
in patient care provide only unsatisfying strategies in diagnostic and treatment
for high-grade gliomas. Here we describe metabolic phenomena in the choline and
glycine network associated with stem cell culture conditions in the classical
glioma cell line U87. Using high-resolution proton magnetic resonance
spectroscopy of cell culture metabolic extracts we compare the metabolic
composition of U87 chronically propagated as adherent culture in medium
supplemented with serum to serum-free neurosphere growth. We found that the
switch to neurosphere growth, besides the increase of cells expressing the
putative glioma stem cell marker CD133, modulated a number of intracellular
metabolites including choline, creatine, glycine, and myo-inositol that have been
previously reported as potential diagnostic markers in various tumours. These
findings highlight the critical influence of culture conditions on glioma cell
metabolism, and therefore particular caution should be drawn to the use of in
vitro system research in order to investigate cancer metabolism.
PMID- 26443313
TI - Ciliary neurotrophic factor protects SH-SY5Y neuroblastoma cells against Abeta1
42-induced neurotoxicity via activating the JAK2/STAT3 axis.
AB - The neurotoxicity of aggregated amyloid beta (Abeta) has been implicated as a
critical cause in the pathogenesis of Alzheimer's disease (AD), which leads to
neuronal cell damage by inducing oxidative stress and consequently triggering
cell apoptosis. Recently, Abeta-dependent inactivation of the Janus tyrosine
kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3)
signaling pathway was found to play a critical role in the memory impairment
related to AD. Previous research indicated that JAK2/STAT3 axis inactivation
might be the result of aberrant reactive oxygen species (ROS) generation induced
by Abeta in neurons. As the JAK2/STAT3 axis is a major transducer of ciliary
neurotrophic factor (CNTF)-mediated neuroprotective activity, this study
extensively evaluated whether activation of the JAK2/STAT3 axis by CNTF was
responsible for the neuroprotective effect of this protein against Abeta1-42
induced cytotoxicity, oxidative injury and cell apoptosis in human SH-SY5Y
neuroblastoma cells. Our data showed that CNTF could attenuate or restore cell
injury induced by Abeta1-42 in human SH-SY5Y neuroblastoma cells through
activating the JAK2/STAT3 signaling pathway. Furthermore, CNTF strikingly
prevented Abeta1-42-induced mitochondrial dysfunction and activation of mitogen
activated protein kinases (MAPKs), an effect that could be potently attenuated by
the specific JAK2 inhibitor AG490. In summary, this study confirmed the detailed
mechanism accounting for CNTF's protective effect against Abeta1-42-induced
cytotoxic events in human SH-SY5Y neuroblastoma cells - information which might
significantly contribute to better understanding of the mechanism of action of
CNTF as well as providing a novel target in AD therapy.
PMID- 26443314
TI - MicroRNA-210 regulates cell proliferation and apoptosis by targeting regulator of
differentiation 1 in glioblastoma cells.
AB - MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate protein
biosynthesis and participate in the pathogenesis of various tumours. Previous
studies have shown that miR-210 is highly expressed in different types of human
cancers, including glioblastoma multiforme (GBM). However, the role that miR-210
plays in GBM remains unclear. Here, we detected the expression and examined the
function of miRNA-210 in GBM cells. Furthermore, we investigated the possible
molecular mechanisms by which miRNA-210 mediates cell proliferation and
apoptosis. Fifteen GBM and five normal brain tissues, in addition to the U87MG
and U251 GBM cell lines, were analysed in this study. We found that miR-210 was
upregulated in GBM tissues and cell lines when compared to normal brain tissue.
Cell counting and flow cytometric assay results demonstrated that upregulation of
miR-210 induced cell proliferation and decreased cell apoptosis, respectively. In
addition, downregulation of miR-210 inhibited cell proliferation and induced
apoptosis. We also detected a miR-210 target, regulator of differentiation 1
(ROD1), which is involved in GBM progression. Knockdown of ROD1 reversed the
growth arrest and apoptosis that were originally induced by miR-210 inhibition.
We propose that miR-210 regulates cell proliferation and apoptosis in GBM cells
by targeting ROD1. Our findings may provide a new potential therapeutic target
for the treatment of GBM.
PMID- 26443315
TI - Occurrence of spontaneous and audiogenic seizures following global brain
ischaemia due to cardiac arrest.
AB - Transient cardiac arrest due to cardiac vessel bundle occlusion was used to
produce a rat model of spontaneous and audiogenic seizures. Among the rats,
spontaneous seizures were present in 64%, and audiogenic seizures could be evoked
in 86%, during two weeks of survival after cardiac arrest, by exposure to a loud
sound produced by rattling keys, beginning one day after the post-ischaemic
injury. Data from literature suggested a key role for GABA-ergic system
widespread dysfunction especially in the hippocampus in post-cardiac arrest onset
of audiogenic seizures. Reduced GABA inhibition in the hippocampus seems
responsible for audiogenic seizures following cardiac arrest. In summary it may
be considered that the occurrence of audiogenic seizures following cardiac arrest
is determined not only by a neuronal loss, especially in the hippocampus, but
also by a condition of synapse modification by a regenerative phenomenon. Data
from our study clearly indicate that global brain ischaemia due to cardiac arrest
may induce the susceptibility to spontaneous and audiogenic seizures, but this
effect is transient.
PMID- 26443316
TI - Rapamycin protects dopaminergic neurons against rotenone-induced cell death in
primary mesencephalic cell culture.
AB - INTRODUCTION: Parkinson's disease is the most common movement disorder,
characterized by a progressive and extensive loss of dopaminergic neurons in the
substantia nigra pars compacta and their terminals in the striatum. So far, only
symptomatic treatment is available, and no cure or disease-modifying drugs exist.
The present study was designed to investigate the neuroprotective effect of
rapamycin, an autophagy inducer, on dopaminergic neurons against rotenone-induced
cell death in primary mesencephalic cell culture. MATERIAL AND METHODS: Primary
mesencephalic cell cultures were prepared from embryonic mouse mesencephala
(OFI/SPF, Vienna, Austria) at gestation day 14. Four sets of cultures were
treated as follows: one was run as an untreated control, a second one was treated
with 20 nM rotenone on the 10th day in vitro (DIV) for 48 h, a third one was co
treated with 20 nM rotenone and rapamycin (1, 10, 100, 1000 nM) on the 10th DIV
for 48 h, and a fourth one was treated with rapamycin alone (1, 10, 100, 1000 nM)
on the 10th DIV for 48 h. On the 12th DIV, cultures were subjected to
immunohistochemistry against tyrosine hydroxylase and to fluorescence staining
using LysoTracker Deep Red, JC-1 and DAPI stains. RESULTS: Exposure of such
cultures to 20 nM rotenone on the 10th DIV for 48 h reduced the number of
dopaminergic neurons by 41% and increased the release of lactate dehydrogenase
(LDH) by 178% above untreated controls. Rapamycin (1, 10, 100, 1000 nM) added
together with rotenone from the 10th to 12th DIV spared dopaminergic neurons by
17% and reduced the release of LDH by 64% at the concentration of 100 nM compared
to rotenone-treated cultures. Activation of an autophagic process by rapamycin
was demonstrated by LysoTracker Deep Red fluorescent dye, as indicated by a shift
to increased red fluorescence. Rapamycin also significantly elevated the
mitochondrial membrane potential (Deltapsim), as shown by an increase of the
red:green fluorescence ratio of JC-1. Increased apoptotic cell death due to
rotenone was lowered by rapamycin, as shown by the blue-fluorescent DAPI nucleic
acid stain. CONCLUSIONS: Our study indicates for the first time that rapamycin,
known as an autophagy inducer, protected dopaminergic neurons against rotenone
induced cell death in primary mesencephalic cell culture.
PMID- 26443317
TI - Investigation of iron's neurotoxicity during cerebral maturation in the neonatal
rat model of haemolysis.
AB - INTRODUCTION: Haemolytic disease of newborns due to rhesus and AB0
incompatibility is encountered frequently in neonatal clinics and may lead to
severe haemolysis. In this study, it is suggested that important amounts of iron
released with haemolysis may have a toxic effect on the brain parenchymal tissue,
and the severity of the toxic effect can be correlated with the maturation of the
brain barrier systems. To demonstrate the accumulation and the neuro-toxic
effects of free iron (Fe) in the brain an experimental haemolysis model with
various maturation phases was performed. MATERIAL AND METHODS: The study was
composed of 48 Wistar rats with the following ages: five days old (Group A), 10
days old (Group B), and 19 days old (Group C). Each group was divided into three
experimental subgroups and three control groups. Experimental groups were treated
with intraperitoneal 75 mg/kg/day phenyl hydrazine hydrochloride for haemolysis.
RESULTS: We demonstrated that the blood brain barrier (BBB) is permeable in five
day-old newborn rats and is mature in 10- and 19-day-old rats. Iron staining and
neuronal damage were detected in group A and group B rats. No damage was detected
in the brain tissue of group C animals. The presence of iron staining and
neuronal damage in group B with mature BBB may suggest the existence of other
incomplete barrier systems different from BBB that lead to iron accumulation in
the brain. CONCLUSIONS: Blood brain barrier has a partial role in Fe transport,
and the alternative barrier systems may also be involved. It could be supposed
that after maturation of all barrier systems, excessive Fe penetration to the
brain cannot occur. Our findings showed that the toxic amounts of iron may
penetrate into the brain parenchyma of newborns despite the BBB preservation and
cause neuronal damage in newborns, but the mature brain is not affected by the
same magnitude blood levels.
PMID- 26443318
TI - Emery-Dreifuss muscular dystrophy type 2 associated (?) with mild peripheral
polyneuropathy.
AB - In recent years numerous mutations in the LMNA gene encoding lamin A/C were shown
to segregate with a wide spectrum of phenotypes. A recurrent p.R377H mutation in
the LMNA gene was reported in patients with Emery-Dreifuss dystrophy (EDMD2) with
various ethnic backgrounds. We present a patient with EDMD2 caused by a p.R377H
mutation, associated with mild peripheral polyneuropathy. The analysis of
peripheral myelin protein 22 (PMP22), ganglioside induced differentiation
associated protein 1 (GDAP1), gap junction beta-1 protein (GJB1), and myelin
protein zero (MPZ) genes did not reveal mutations; however, we identified a new
sequence intronic variant in the mitofusin 2 (MFN2) gene of unknown pathogenic
significance. A complex phenotype in the presented patient might depend either on
single mutation in the LMNA gene or on bigenic defect; therefore, a wide genetic
investigation is needed to elucidate the molecular background of
EDMD2/polyneuropathy in this case.
PMID- 26443319
TI - Schwannoma of the medial cutaneous nerve of the arm: a rare location with
concomitant compression neuropathy of the ulnar nerve.
AB - The objective of this paper is to present a case of rare location of schwannoma
in the medial cutaneous nerve of the arm at the level of the axilla. Preliminary
diagnostic examination of the tumour was carried out in another hospital by means
of open biopsy. In the preoperative period symptoms of ulnar nerve dysfunction
(paraesthesias, positive Hoffmann-Tinel sign) dominated the clinical picture.
After having performed imaging studies and electromyographic (EMG) examination,
the patient was scheduled for an operation. The tumour, measuring 3.5 * 3.0 * 1.5
cm, was resected without damage to the fascicular structure. Presence of
paraesthesias in the distribution of the medial cutaneous nerve of the arm, which
was first noted in the postoperative period, persists in moderate severity until
now. As a result of the performed operative treatment, such symptoms as palpable
tumour mass, pain, paraesthesias in the ulnar nerve distribution and positive
Hoffmann-Tinel sign resolved. On the basis of histopathological examination
results the final diagnosis of classical schwannoma was established.
PMID- 26443320
TI - Comparison Between Dual-Energy Computed Tomography and Ultrasound in the
Diagnosis of Gout of Various Joints.
AB - RATIONALE AND OBJECTIVES: Dual-energy computed tomography (DECT) and ultrasound
are both used to assess gouty arthritis. The present study was designed to
compare the diagnostic accuracy of DECT and ultrasound in detecting monosodium
urate (MSU) crystal deposition in various joints. MATERIALS AND METHODS: This
study enrolled 40 patients diagnosed with acute gouty arthritis. All affected and
contralateral joints were scanned (128 in total) using both DECT and ultrasound
to determine the MSU deposition in upper limbs (wrist and elbow) and lower limbs
(the first metatarsophalangeal joints, ankles, and knee). The MSU crystal
accumulation detected by each method was compared for various joints. RESULTS:
The 128 scanned joints included 52 of the upper limbs and 76 of the lower limbs.
For the upper limbs, the percentage of MSU crystal accumulation detected by DECT
(22/52, 42.3%) was significantly higher than that by ultrasound (10/52, 19.2%; P
= .0027). The detection rates of the two methods for the lower limbs were similar
(P = .3173). CONCLUSIONS: For detection of MSU crystal deposition in the upper
limb joints, DECT was superior to ultrasound, whereas there was no difference
between the two methods for the lower limbs. Therefore, ultrasound can be used
for primary screening, and DECT afterward. Although the modalities are similar in
making the initial diagnosis, DECT is far superior at displaying the anatomic
extent of the disease.
PMID- 26443321
TI - Scientific evidence for health effects attributed to the consumption of
probiotics and prebiotics: an update for current perspectives and future
challenges.
AB - Probiotics and prebiotics, mainly commercialised as food ingredients and also as
supplements, are considered highly profitable niche markets. However, in recent
years, the food industry has suffered from a series of health claim restrictions
on probiotics and prebiotics in many parts of the world, including those made by
the European Food Safety Authority. Therefore, we reviewed the core benefits of
probiotic and prebiotic consumption on health. A number of studies have examined
the prevention and/or management of intestinal infections, respiratory tract
infections, CVD, osteoporosis, urogenital infections, cavities, periodontal
disease and halitosis, allergic reactions, inflammatory bowel disease and
irritable bowel syndrome and Helicobacter pylori gastric infections. In fact, a
deeper understanding of the mechanisms involved in human microbiota and immune
system modulation by probiotics and prebiotics relies on continuous efforts to
establish suitable biomarkers of health and diseases risk factors for the design
of clinical trials required for health claim approval. In spite of the promising
results, the performance of large, long-term, well-planned, well-aligned clinical
studies is crucial to provide more reliability and a more solid basis for the
outcomes achieved and to support the potential use of probiotics and prebiotics
in clinical practice.
PMID- 26443323
TI - Seismological constraints on the crustal structures generated by continental
rejuvenation in northeastern China.
AB - Crustal rejuvenation is a key process that has shaped the characteristics of
current continental structures and components in tectonic active continental
regions. Geological and geochemical observations have provided insights into
crustal rejuvenation, although the crustal structural fabrics have not been well
constrained. Here, we present a seismic image across the North China Craton (NCC)
and Central Asian Orogenic Belt (CAOB) using a velocity structure imaging
technique for receiver functions from a dense array. The crustal evolution of the
eastern NCC was delineated during the Mesozoic by a dominant low seismic wave
velocity with velocity inversion, a relatively shallow Moho discontinuity, and a
Moho offset beneath the Tanlu Fault Zone. The imaged structures and geochemical
evidence, including changes in the components and ages of continental crusts and
significant continental crustal growth during the Mesozoic, provide insight into
the rejuvenation processes of the evolving crust in the eastern NCC caused by
structural, magmatic and metamorphic processes in an extensional setting. The
fossil structural fabric of the convergent boundary in the eastern CAOB indicates
that the back-arc action of the Paleo-Pacific Plate subduction did not reach the
hinterland of Asia.
PMID- 26443322
TI - Sleep-based memory processing facilitates grammatical generalization: Evidence
from targeted memory reactivation.
AB - Generalization-the ability to abstract regularities from specific examples and
apply them to novel instances-is an essential component of language acquisition.
Generalization not only depends on exposure to input during wake, but may also
improve offline during sleep. Here we examined whether targeted memory
reactivation during sleep can influence grammatical generalization. Participants
gradually acquired the grammatical rules of an artificial language through an
interactive learning procedure. Then, phrases from the language (experimental
group) or stimuli from an unrelated task (control group) were covertly presented
during an afternoon nap. Compared to control participants, participants re
exposed to the language during sleep showed larger gains in grammatical
generalization. Sleep cues produced a bias, not necessarily a pure gain,
suggesting that the capacity for memory replay during sleep is limited. We
conclude that grammatical generalization was biased by auditory cueing during
sleep, and by extension, that sleep likely influences grammatical generalization
in general.
PMID- 26443324
TI - Detoxification of hostplant's chemical defence rather than its anti-predator co
option drives beta-glucosidase-mediated lepidopteran counteradaptation.
AB - The evolutionary plant-herbivore arms race sometimes gives rise to remarkably
unique adaptation strategies. Here we report one such strategy in the
lepidopteran herbivore Manduca sexta against its hostplant Nicotiana attenuata's
major phytotoxins, 17-hydroxygeranyllinalool diterpene glycoside, lyciumoside IV
and its malonylated forms. We show that alkalinity of larval regurgitant non
enzymatically demalonylates the malonylated forms to lyciumoside IV. Lyciumoside
IV is then detoxified in the midgut by beta-glucosidase 1-catalysed
deglycosylation, which is unusual, as typically the deglycosylation of
glycosylated phytochemicals by insects results in the opposite: toxin activation.
Suppression of deglucosylation by silencing larval beta-glucosidase 1 by plant
mediated RNAi causes moulting impairments and mortality. In the native habitat of
N. attenuata, beta-glucosidase 1 silencing also increases larval unpalatability
to native predatory spiders, suggesting that the defensive co-option of
lyciumoside IV may be ecologically advantageous. We infer that M. sexta
detoxifies this allelochemical to avoid its deleterious effects, rather than co
opting it against predators.
PMID- 26443325
TI - Representativeness of the German National Register for Congenital Heart Defects:
a clinically oriented analysis.
AB - BACKGROUND: Approximately 6000 children are born with CHD in Germany each year.
It is increasingly rare that these children die from their chronic illness. In
the present study, data recorded in the National Register for Congenital Heart
Defects with respect to the prevalence of specific lesions and sex distribution
are compared with that recorded in a published German prevalence study
(Prevalence Study) and with the meta-analysis by van der Linde et al. METHODS: A
descriptive data analysis was performed using a minimal data set. The demographic
data included sex and birth year; the medical data comprised the cardiovascular
diagnosis according to the short list of the International Paediatric and
Congenital Cardiac Code. RESULTS: As the data analysis shows, the National
Register is a clinical register including primarily clinical cases/cases relevant
to healthcare. The prevalence values and sex ratios recorded in the register are
closer to the values given in the literature than those determined by the
Prevalence Study. Severe CHD was slightly over-represented in the National
Register compared with the van der Linde et al meta-analysis. The deviations with
respect to prevalence values are within an acceptable range. CONCLUSION: With its
48,000 patients, the National Register plays a unique and important role for
research in the field of CHD. Samples from the National Register can be used as a
gold standard for future studies, as the patient population registered in it can
be considered representative of CHD in Germany and Europe.
PMID- 26443326
TI - A splicing variant of Merlin promotes metastasis in hepatocellular carcinoma.
AB - Merlin, which is encoded by the tumour suppressor gene Nf2, plays a crucial role
in tumorigenesis and metastasis. However, little is known about the functional
importance of Merlin splicing forms. In this study, we show that Merlin is
present at low levels in human hepatocellular carcinoma (HCC), particularly in
metastatic tumours, where it is associated with a poor prognosis. Surprisingly, a
splicing variant of Merlin that lacks exons 2, 3 and 4 ((Delta2-4)Merlin) is
amplified in HCC and portal vein tumour thrombus (PVTT) specimens and in the
CSQT2 cell line derived from PVTT. Our studies show that (Delta2-4)Merlin
interferes with the capacity of wild-type Merlin to bind beta-catenin and ERM,
and it is expressed in the cytoplasm rather than at the cell surface.
Furthermore, (Delta2-4)Merlin overexpression increases the expression levels of
beta-catenin and stemness-related genes, induces the epithelium-mesenchymal
transition phenotype promoting cell migration in vitro and the formation of lung
metastasis in vivo. Our results indicate that the (Delta2-4)Merlin variant
disrupts the normal function of Merlin and promotes tumour metastasis.
PMID- 26443327
TI - Barriers to guideline-concordant antibiotic use among inpatient physicians: A
case vignette qualitative study.
AB - BACKGROUND: Greater adherence to antibiotic-prescribing guidelines may promote
more judicious antibiotic use, which could benefit individual patients and
society at large. OBJECTIVE: To assess physician knowledge and acceptance of
antibiotic-prescribing guidelines through the use of case vignettes. DESIGN: We
conducted semistructured interviews with 30 inpatient physicians. Participants
were asked to respond to 3 hypothetical case vignettes: (1) a skin and soft
tissue infection (SSTI), (2) suspected hospital-acquired pneumonia (HAP), and (3)
asymptomatic bacteriuria (ASB). All participants received feedback according to
guidelines from the Infectious Diseases Society of America (IDSA) and were asked
to discuss their level of comfort with following these guidelines. SETTING: Two
acute care teaching hospitals for adult patients. INTERVENTION: None.
MEASUREMENTS: Data from transcribed interviews were analyzed using emergent
thematic analysis. RESULTS: Participants were receptive to guidelines and
believed they were useful. However, participants' responses to the case vignettes
demonstrated that IDSA guideline recommendations were not routinely followed for
SSTI, HAP, and ASB. We identified 3 barriers to guideline-concordant care: (1)
physicians' lack of awareness of specific guideline recommendations; (2) tension
between adhering to guidelines and the desire to individualize patient care; and
(3) skepticism of certain guideline recommendations. CONCLUSIONS: Case vignettes
may be useful tools to assess physician knowledge and acceptance of antibiotic
prescribing guidelines. Using case vignettes, we identified 3 barriers to
following IDSA guidelines. Efforts to improve guideline-concordant antibiotic
prescribing should focus on reducing such barriers at the local level.
PMID- 26443328
TI - CD38 Monoclonal Antibody Therapies for Multiple Myeloma.
AB - The goal of this review is to provide historical, recent preclinical, and current
clinical summaries of efforts to understand the CD38 molecule and to develop
monoclonal antibodies that target it. We focus particularly on efforts involving
multiple myeloma, a malignancy of terminally differentiated B cells that remains
incurable despite many advances. An era of anti-CD38 monoclonal antibody therapy
for myeloma is approaching, one that, we hope, will enable patients to live
longer and better lives.
PMID- 26443330
TI - [Clinical forensic imaging. Detection and documentation of internal injuries in
living victims of violence].
AB - External examination of the body surface with documentation of all visible
findings can still be regarded as the status quo of clinical forensic injury
assessment. It is obvious that internal findings cannot be detected using this
technique. For obtaining such findings accessible well-established radiological
techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI)
should be used. Especially MRI with no damaging radiation exposure for the
examined person allows the detection of internal soft tissue and organ damage and
offers a great potential regarding new techniques for allowing insights into
tissue composition and function. Furthermore, imaging data collected in clinical
institutions before the patient was transferred to the department of legal
medicine will play a major role in the future. Although these data were obtained
based on a different approach, they provide excellent and recent information on
injuries in the respective (current) case und can therefore be of high value for
the forensic expertise.
PMID- 26443329
TI - [SENDS criteria from the diversification of MAST procedures. Implementation of
preoperative simulation].
AB - CLINICAL ISSUE: Minimal access spinal technologies (MAST) lead to a
diversification of surgical procedures, which requires careful selection of the
procedure and outcome monitoring. For a rational selection of the procedure
simulation, endoscopy, navigation, decompression and stabilization (SENDS)
criteria can be derived from the development of the MAST procedures. Preoperative
simulation has diagnostic and therapeutic values. The SENDS criteria can be
verified indirectly via outcome control. STANDARD TREATMENT: Biomechanically
meaningful diagnostic x-rays of the spinal segment to be surgically treated are
currently carried out with the patient in inclination and reclination. TREATMENT
INNOVATIONS: Software-related preoperative simulation based on these x-ray images
facilitates the selection and implementation of the MAST procedure. DIAGNOSTIC
WORK-UP: For preoperative simulation motion shots are needed in inclination,
neutral position and reclination and the dimensions can be obtained using an x
ray ball or a computed tomography (CT) scan. PERFORMANCE: The SENDS criteria are
useful because established procedures based on these criteria reach a comparable
outcome. Preoperative simulation appears to be a useful selection criterion.
ACHIEVEMENTS: Preoperatively it is necessary to collate patient and segment
information in order to provide each patient with individualized treatment. So
far there is no evidence for a better outcome after preoperative simulation but a
reduction of surgery time and intraoperative radiation exposure could already be
demonstrated. PRACTICAL RECOMMENDATIONS: Minimally invasive methods should be
preferred if there is a comparable outcome. The establishment of new procedures
has to be accompanied by the maintenance of a spine register. Minimally invasive
surgical procedures should be individualized for each patient and segment.
Mobility X-ray images should be prepared for use with the preoperative simulation
as the information content significantly increases with respect to the MAST
procedure.
PMID- 26443331
TI - Shifts in leaf N:P stoichiometry during rehabilitation in highly alkaline bauxite
processing residue sand.
AB - Large quantities of sodic and alkaline bauxite residue are produced globally as a
by-product from alumina refineries. Ecological stoichiometry of key elements
[nitrogen (N) and phosphorus (P)] plays a critical role in establishing
vegetation cover in bauxite residue sand (BRS). Here we examined how changes in
soil chemical properties over time in rehabilitated sodic and alkaline BRS
affected leaf N to P stoichiometry of native species used for rehabilitation.
Both Ca and soil pH influenced the shifts in leaf N:P ratios of the study species
as supported by consistently significant positive relationships (P < 0.001)
between these soil indices and leaf N:P ratios. Shifts from N to P limitation
were evident for N-fixing species, while N limitation was consistently
experienced by non-N-fixing plant species. In older rehabilitated BRS
embankments, soil and plant indices (Ca, Na, pH, EC, ESP and leaf N:P ratios)
tended to align with those of the natural ecosystem, suggesting improved
rehabilitation performance. These findings highlight that leaf N:P stoichiometry
can effectively provide a meaningful assessment on understanding nutrient
limitation and productivity of native species used for vegetating highly sodic
and alkaline BRS, and is a crucial indicator for assessing ecological
rehabilitation performance.
PMID- 26443332
TI - Contrasting microbial biogeographical patterns between anthropogenic subalpine
grasslands and natural alpine grasslands.
AB - The effect of plant species composition on soil microbial communities was studied
at the multiregional level. We compared the soil microbial communities of alpine
natural grasslands dominated by Carex curvula and anthropogenic subalpine
pastures dominated by Nardus stricta. We conducted paired sampling across the
Carpathians and the Alps and used Illumina sequencing to reveal the molecular
diversity of soil microbes. We found that bacterial and fungal communities
exhibited contrasting regional distributions and that the distribution in each
grassland is well discriminated. Beta diversity of microbial communities was much
higher in C. curvula grasslands due to a marked regional effect. The composition
of grassland-type core microbiomes suggest that C. curvula, and N. stricta to a
lesser extent, tend to select a cohort of microbes related to
antibiosis/exclusion, pathogenesis and endophytism. We discuss these findings in
light of the postglacial history of the studied grasslands, the habitat
connectivity and the disturbance regimes. Human-induced disturbance in the
subalpine belt of European mountains has led to homogeneous soil microbial
communities at large biogeographical scales. Our results confirm the overarching
role of the dominant grassland plant species in the distribution of microbial
communities and highlight the relevance of biogeographical history.
PMID- 26443333
TI - Advancing a distributed multi-scale computing framework for large-scale high
throughput discovery in materials science.
AB - We describe the development of a large-scale high-throughput application for
discovery in materials science. Our point of departure is a computational
framework for distributed multi-scale computation. We augment the original
framework with a specialized module whose role is to route evaluation requests
needed by the high-throughput application to a collection of available
computational resources. We evaluate the feasibility and performance of the
resulting high-throughput computational framework by carrying out a high
throughput study of battery solvents. Our results indicate that distributed multi
scale computing, by virtue of its adaptive nature, is particularly well-suited
for building high-throughput applications.
PMID- 26443334
TI - Eye care services for the populations of remote districts in eastern Taiwan: a
practical framework using a Mobile Vision Van Unit.
AB - INTRODUCTION: To put a blindness prevention program into practice in remote
districts of Eastern Taiwan, a Mobile Vision Van Unit (MVVU) was established to
work as a community eyecare station. The aim of this study was to describe the
operation and challenges encountered with this unit and its efficacy in expanding
eyecare services. METHODS: A population-based primary eyecare model was applied
to a population in remote regions of eastern Taiwan. An MVVU, equipped with an
autorefractometer, a non-contact tonometer, a slit-lamp biomicroscope, a
retinoscope, an ophthalmoscope and a mini optician workshop was taken into remote
areas of eastern Taiwan to provide comprehensive eyecare services. An integrated
vertical referral system for further diagnosis and treatment was also employed.
Data including the services provided, spectacles dispensed, health promotion
activities conducted and the effectiveness of the model were collected and
analysed. The main outcome measures were practicability of a primary eyecare
model, prevalence of visual impairment and the major causes in middle-aged and
elderly patients. RESULTS: Between 2002 and 2008, a total of 600 primary eyecare
services were delivered to 28 indigenous villages and remote townships in eastern
Taiwan. The MVVU screened a total of 35 275 inhabitants. The ages of those
screened ranged from preschool children to the elderly, and 2073 patients were
referred to secondary or tertiary centres in the middle-aged and elderly
blindness prevention program. On-site dispensing of low-cost spectacles and the
rapid delivery of more complex prescriptions were provided without charge to 1816
participants who could not afford glasses. In addition, 118 eye health
educational programs and training courses for paramedical personnel and
volunteers were conducted. CONCLUSIONS: An MVVU model for blindness prevention is
highly feasible in its efficiency and cost-effectiveness in communities with
deficient medical resources.
PMID- 26443335
TI - Nanothermometry: From Microscopy to Thermal Treatments.
AB - Measuring temperature in cells and tissues remotely, with sufficient sensitivity,
and in real time presents a new paradigm in engineering, chemistry and biology.
Traditional sensors, such as contact thermometers, thermocouples, and electrodes,
are too large to measure the temperature with subcellular resolution and are too
invasive to measure the temperature in deep tissue. The new challenge requires
novel approaches in designing biocompatible temperature sensors-nanothermometers
and innovative techniques for their measurements. In the last two decades, a
variety of nanothermometers whose response reflected the thermal environment
within a physiological temperature range have been identified as potential
sensors. This review covers the principles and aspects of nanothermometer design
driven by two emerging areas: single-cell thermogenesis and image guided thermal
treatments. The review highlights the current trends in nanothermometry
illustrated with recent representative examples.
PMID- 26443336
TI - Is consuming yoghurt associated with weight management outcomes? Results from a
systematic review.
AB - BACKGROUND: Yoghurt is part of the diet of many people worldwide and is commonly
recognised as a 'health food'. Epidemiological studies suggest that yoghurt may
be useful as part of weight management programs. In the absence of comprehensive
systematic reviews, this systematic review investigated the effect of yoghurt
consumption by apparently healthy adults on weight-related outcomes. METHODS: An
extensive literature search was undertaken, as part of a wider scoping review, to
identify yoghurt studies. A total of 13 631 records were assessed for their
relevance to weight-related outcomes. RESULTS: Twenty-two publications were
eligible according to the review protocol. Cohort studies (n=6) and cross
sectional studies (n=7) all showed a correlation between yoghurt and lower or
improved body weight/composition. Six randomised controlled trials (RCTs) and one
controlled trial had various limitations, including small size and short
duration. One RCT showed significant effects of yoghurt on weight loss, but was
confounded by differences in calcium intake. One trial showed nonsignificant
weight gain and the remaining five trials showed nonsignificant weight losses
that were greater in yoghurt consumers. CONCLUSIONS: Yoghurt consumption is
associated with lower body mass index, lower body weight/weight gain, smaller
waist circumference and lower body fat in epidemiological studies. RCTs suggest
weight reduction effects, but do not permit determination of a cause-effect
relationship. Well-controlled, adequately powered trials in research and
community settings appear likely to identify a modest but beneficial effect of
yoghurt consumption for prevention of weight gain and management of obesity. The
ready availability of yoghurt (a nutrient-dense food) and its ease of
introduction to most diets suggests that educating the public to eat yoghurt as
part of a balanced and healthy diet may potentially contribute to improved public
health. Future carefully designed RCTs could provide proof of principle and large
community-based studies could determine the practical impact of yoghurt on body
weight/composition.
PMID- 26443337
TI - Interplay of atherogenic factors, protein intake and betatrophin levels in obese
metabolic syndrome patients treated with hypocaloric diets.
AB - CONTEXT: The understanding of the potential role of betatrophin in human
metabolic disorders is a current challenge. OBJECTIVE: The present research
evaluated circulating betatrophin levels in obese patients with metabolic
syndrome (MetSyn) features under energy-restricted weight-loss programs and in
normal weight in order to establish the putative interplay between the levels of
this hormone, diet and metabolic risk factors linked to obesity and associated
comorbidities. SUBJECTS AND METHODS: One hundred forty-three participants were
enrolled in the study (95 obese-MetSyn; age 49.5+/-9.4 years; body mass index
(BMI) 35.7+/-4.5 kg m(-2) and 48 normal weight; age 35.71+/-8.8 years; BMI 22.9+/
2.2 kg m(-2)). A nutritional therapy consisting in two hypocaloric strategies
(control diet based on the AHA recommendations and the RESMENA (MEtabolic
Syndrome REduction in Navarra) diet, a novel dietary program with changes in the
macronutrient distribution) was only prescribed to obese-MetSyn participants who
were randomly allocated to the dietary strategies. Dietary records,
anthropometrical and biochemical variables as well as betatrophin levels were
analyzed before (pre-intervention, week 0), at 8 weeks (post-intervention, week
8) and after 4 additional months of self-control period (follow-up, week 24).
RESULTS: Betatrophin levels were higher in obese-MetSyn patients than normal
weight subjects (1.24+/-0.43 vs 0.97+/-0.69 ng ml(-1), respectively, P=0.012),
and levels were positively associated with body composition, metabolic
parameters, leptin and irisin in all participants at baseline. Notably, low pre
intervention (week 0) betatrophin levels in obese patients were significantly
associated with higher dietary-induced changes in atherogenic risk factors after
8 weeks. Moreover, protein intake, especially proteins from animal sources, was
an independent determinant of betatrophin levels after dietary treatment (B=
0.27; P=0.012). CONCLUSIONS: Betatrophin is elevated in obese patients with
MetSyn features and is associated with poorer nutritional outcomes of adiposity
and dyslipidemia traits after a weight-loss program. Dietary protein intake could
be a relevant modulator of betatrophin secretion and activity.
PMID- 26443338
TI - Waist-to-height ratio centiles by age and sex for Japanese children based on the
1978-1981 cross-sectional national survey data.
AB - OBJECTIVES: To construct waist-to-height ratio (WC/Ht) reference values and
centile curves for Japanese children and to compare these references with those
from other countries. METHODS: The 1978-1981 national survey data were used for
reference and the 1992-1994 national survey data were used for validation. The
former included 19 233 children, and the latter included 10 446 children, aged 6
to 18 years. Waist circumferences (WC) were measured at the level of maximum
waist narrowing in girls, and at the level of the top of the iliac crest in boys.
Age- and sex-specific reference curves were fitted with the LMS method. Cut-off
points were arbitrarily set at 85th, 90th, 95th and 97th centiles, and compared
with WC/Ht 0.50. RESULTS: The proportion of children in whom WC/Ht exceeded 0.50
was 18.7% of boys and 1.9% of girls, whereas the proportion of children exceeding
90th centile was 42.4% for boys and 17.3% for girls. The reference values
decreased with age in girls but varied by age without a clear trend in boys.
CONCLUSIONS: The first reference values for WC/Ht are provided for Japanese youth
based on the 1978-1981 national survey data. These curves are age- and sex
dependent, precluding the use of universal cut-off for WC/Ht of 0.50.
PMID- 26443339
TI - Wheat gluten intake increases weight gain and adiposity associated with reduced
thermogenesis and energy expenditure in an animal model of obesity.
AB - BACKGROUND/OBJECTIVES: The association between gluten and body weight is
inconsistent. Previously, we showed that a gluten-free diet reduces weight gain
without changing food intake in mice fed high-fat diets. In the present study, we
investigated the effects of gluten intake on fat metabolism, thermogenesis and
energy expenditure in mice fed a standard or high-fat diet. METHODS: Mice were
fed four different experimental diets during 8 weeks: a control-standard diet
(CD), a CD added with 4.5% of wheat gluten (CD-G), a high-fat diet (HFD) and a
HFD added with 4.5% of wheat gluten (HFD-G). After 8 weeks, the mice received
(99m)Tc-radiolabeled gluten orally to study gluten absorption and biodistribution
or they underwent indirect calorimetry. After killing, subcutaneous and brown
adipose tissues (SAT and BAT) were collected to assess thermogenesis-related
protein expression. Lipid metabolism was studied in adipocyte cultures from the
four groups. RESULTS: Despite having had the same energy intake, CD-G and HFD-G
mice exhibited increased body weight and fat deposits compared with their
respective controls. (99m)Tc-GLU or its peptides were detected in the blood,
liver and visceral adipose tissue, suggesting that gluten can even reach
extraintestinal organs. Uncoupling protein-1 expression was reduced in the BAT of
HFD-G and in the SAT of CD-G and HFD-G mice. Indirect calorimetry showed lower
oxygen volume consumption in CD-G and HFD-G groups compared with their controls.
In HFD mice, daily energy expenditure was reduced with gluten intake. Gluten also
reduced adiponectin, peroxisome proliferator-activated receptor (PPAR)-alpha and
PPARgamma and hormone-sensitive lipase in cultures of isolated adipocytes from
HFD mice, whereas in the CD-G group, gluten intake increased interleukin-6
expression and tended to increase that of tumor necrosis factor. CONCLUSIONS:
Wheat gluten promotes weight gain in animals on both HFD and CD, partly by
reducing the thermogenic capacity of adipose tissues.
PMID- 26443340
TI - Saturation of subcutaneous adipose tissue expansion and accumulation of ectopic
fat associated with metabolic dysfunction during late and post-pubertal growth.
AB - BACKGROUND/OBJECTIVE: Puberty is a period defined by large changes in adipose
tissue accumulation and distribution; however, longitudinal patterns of ectopic
fat development have not been shown. We have previously shown significant
declines in beta-cell function (BCF) across puberty and hypothesize that
accumulation of ectopic fat deposition, particularly hepatic fat, will predict
this fall. SUBJECT/METHODS: We conducted a longitudinal study and examined 2-year
change in abdominal fat distribution and type 2 diabetes risk markers in 76
Hispanic children and young adults (16.1+/-0.5 years, 66% obese, 52% male, 51%
post-pubertal). Subcutaneous abdominal adipose tissue (SAAT), visceral adipose
tissue (VAT), hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were
measured by 3-Tesla magnetic resonance imaging, and markers of type 2 diabetes
risk were collected at fasting and during an oral glucose tolerance test (OGTT).
RESULTS: Baseline pubertal status significantly moderated the 2-year change in
ectopic fat deposition, such that VAT, HFF and PFF increased in individuals
during late and post-pubertal growth, whereas children earlier in their pubertal
development decreased ectopic accumulation and had less VAT accumulation (VAT:
pTanner*time=0.044, 0.31+/-0.08 l vs 0.03+/-0.10 l; HFF: pTanner*time=0.007,
1.34+/-0.87% vs -2.61+/-1.11%; PFF: pTanner*time<0.001, 1.61+/-0.39% vs -0.96+/
0.50%). Independent of pubertal status, the 2-year increase in HFF and VAT
significantly associated with a decline in BCF (beta=-1.04, P=0.038; beta=-1.81,
P=0.020) and metabolic function, while accumulation of SAAT significantly
associated with BCF (beta=1.36, P=0.012) and metabolic improvement. HFF
accumulation was the only depot to significantly predict clinical markers of type
2 diabetes risk, fasting glucose and HbA1c, and circulating free fatty acid
levels (beta=1.00, P=0.034; beta=1.00, P=0.015; beta=01.01, P=0.024).
CONCLUSIONS: The accumulation of SAAT defends against type 2 diabetes risk and
potentially ectopic fat accumulation. Intra-abdominal VAT and HFF accumulation
both associate with metabolic decline and BCF, while HFF predicts an even greater
number of metabolic risk features.
PMID- 26443341
TI - Measuring perceived exercise capability and investigating its relationship with
childhood obesity: a feasibility study.
AB - BACKGROUND/OBJECTIVES: According to the COM-B ('Capability', 'Opportunity',
'Motivation' and 'Behaviour') model of behaviour, three factors are essential for
behaviour to occur: capability, opportunity and motivation. Obese children are
less likely to feel capable of exercising. The implementation of a new
methodological approach to investigate the relationship between perceived
exercise capability (PEC) and childhood obesity was conducted, which involved
creating a new instrument, and demonstrating how it can be used to measure
obesity intervention outcomes. SUBJECTS/METHODS: A questionnaire aiming to
measure perceived exercise capability, opportunity and motivation was
systematically constructed using the COM-B model and administered to 71 obese
children (aged 9-17 years (12.24+/-0.2.01), body mass index (BMI) standard
deviation scores (SDS) 2.80+/-0.660) at a weight-management camp in northern
England. Scale validity and reliability was assessed. Relationships between PEC,
as measured by the questionnaire, and BMI SDS were investigated for the children
at the weight-management camp, and for 45 Spanish schoolchildren (aged 9-13
years, (10.52+/-1.23), BMI SDS 0.80+/-0.99). A pilot study, demonstrating how the
questionnaire can be used to measure the effectiveness of an intervention aiming
to bring about improved PEC for weight-management camp attendees, was conducted.
No participants withdrew from these studies. RESULTS: The questionnaire domain
(exercise capability, opportunity and motivation) composite scales were found to
have adequate internal consistency (a=0.712-0.796) and construct validity
(chi(2)/degrees of freedom=1.55, root mean square error of approximation=0.072,
comparative fit index=0.92). Linear regression revealed that low PEC was
associated with higher baseline BMI SDS for both UK (b=-0.289, P=0.010) and
Spanish (b=-0.446, P=0.047) participants. Pilot study findings provide
preliminary evidence for PEC improvements through intervention being achievable,
and measurable using the questionnaire. CONCLUSIONS: Evidence is presented for
reliability and validity of the questionnaire, and for feasibility of its use in
the context of a childhood obesity intervention. Future research could
investigate the link between PEC and childhood obesity further.
PMID- 26443342
TI - Secreted factors derived from obese visceral adipose tissue regulate the
expression of breast malignant transformation genes.
AB - BACKGROUND/OBJECTIVES: Obese adipose tissue, especially the visceral depot,
exhibits altered production of several molecules that could have a role on the
initiation/promotion of breast cancer development. The aim of this work was to
evaluate the effect of excess adipose tissue and its secreted factors on the
expression of genes involved in the early steps of tumor promotion on the mammary
gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated
in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats
and circulating leukocytes isolated from a group of breast cancer diagnosed and
non-diagnosed obese women and compared with their normal weight counterparts. In
addition, the human non-tumoral mammary epithelial cell line MCF10A was treated
in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or
subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the
lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were
classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R)
according to the maximum fat mass gain of the lean group as a cut-off. As
compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower
lean mass. The anatomical characteristic of DIO-S was correlated with
differential expression of cellular proliferation (ALDH3A1 and MYC) and
antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN,
TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was
reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the
lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in
leukocytes from obese women compared with normal weight women without evidence of
breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral
adipose tissue could be among the relevant factors that promote changes involved
in the early steps of tumor development in mammary gland. These changes can be
detected even before histological alterations and in circulating leukocytes.
PMID- 26443344
TI - Accuracy of abdominal ultrasound for the diagnosis of pneumoperitoneum in
patients with acute abdominal pain: a pilot study.
AB - BACKGROUND: Pneumoperitoneum is a rare cause of abdominal pain characterized by a
high mortality. Ultrasonography (US) can detect free intraperitoneal air;
however, its accuracy remains unclear. The aims of this pilot study were to
define the diagnostic performance and the reliability of abdominal US for the
diagnosis of pneumoperitoneum. METHODS: This was a prospective observational
study. Four senior and two junior physicians were shown, in an unpaired
randomized order, abdominal US videos from 11 patients with and 11 patients
without pneumoperitoneum. Abdominal US videos were obtained from consecutive
patients presenting to ED complaining abdominal pain with the diagnosis of
pneumoperitoneum established by CT. Abdominal US was performed according to a
standardized protocol that included the following scans: epigastrium, right and
left hypochondrium, umbilical area and right hypochondrium with the patient lying
on the left flank. We evaluated accuracy, intra- and inter-observer agreement of
abdominal US when reviewed by senior physicians. Furthermore, we compared the
accuracy of a "2 scan-fast exam" (epigastrium and right hypochondrium) vs the
full US examination and the accuracy of physicians expert in US vs nonexpert
ones. Finally, accuracy of US was compared with abdominal radiography in patients
with available images. RESULTS: Considering senior revision, accuracy of
abdominal US was 88.6 % (95 % CI 79.4-92.4 %) with a sensitivity of 95.5 % (95 %
CI 86.3-99.2 %) and a specificity of 81.8 % (95 % CI 72.6-85.5 %). Inter- and
intra-observer agreement (k) were 0.64 and 0.95, respectively. Accuracy of a "2
scan-fast exam" (87.5 %, 95 % CI 77.9-92.4 %) was similar to global exam.
Sensitivity of abdominal radiography (72.2 %, 95 % CI 54.8-85.7 %) was lower than
that of abdominal US, while specificity (92.5 %, 95 % CI 79.5-98.3 %) was higher.
Accuracy (68.2 %, 95 % CI 51.4-80.9 %) of junior reviewers evaluating US was
lower than senior reviewers. CONCLUSIONS: Senior physicians can recognize US
signs of pneumoperitoneum with a good accuracy and reliability; sensitivity of US
could be superior to abdominal radiography and a 2 fast-scan exam seems as
accurate as full abdominal examination. US could be a useful bedside screening
test for pneumoperitoneum. Trial registry ClinicalTrials.gov; No.: NCT02004925;
URL: http://www.clinicaltrials.gov.
PMID- 26443343
TI - Body mass index and breast cancer: analysis of a nation-wide population-based
prospective cohort study on 1 393 985 Taiwanese women.
AB - BACKGROUND: Asian women have a younger age at onset of breast cancer and a lower
body mass index (BMI) than Western women. The link between obesity and risk of
breast cancer in Asian women is still elusive. We aimed to investigate the effect
of BMI on the risk of incident breast cancer in Taiwanese women. METHODS: A total
of 1,393,985 women who had been cancer-free before recruitment and attended a
nation-wide Taiwanese breast cancer-screening program between 1999 and 2009 were
enrolled using a prospective cohort study. Obesity and other relevant variables
(such as menopause status and other biochemical markers) were collected through
in-person interviews, anthropometric measurements and blood samples at first
screen. Incident breast cancers during follow-up were ascertained through the
linkage of the cohort with the National Cancer Registry and the National Death
Certification System. RESULTS: A total of 6969 and 7039 incident breast cancer
cases were identified among women enrolled before and after menopause,
respectively. Compared with a BMI range of 18.5-23.9 kg m(-)(2), the incremental
level of BMI in the enrolled women before menopause revealed a lack of
statistically significant association with the risk of incident breast cancer
(adjusted hazard ratio=0.94, 0.98, 1.02, 1.01 and 0.82 for BMI <18.5, 24-26.9, 27
29.9, 30-34.9 and ?35, respectively), but the incremental level of BMI in the
enrolled women after menopause led to a statistically significant incremental
increase in the risk of breast cancer (adjusted hazard ratio=0.78, 1.19, 1.31,
1.53 and 1.65 for BMI <18.5, 24-26.9, 27-29.9, 30-34.9 and ?35, respectively)
after adjusting for other explanatory risk factors. CONCLUSION: Obesity acts
mainly as an influential promoter of the development of late-onset breast cancer
after menopause in Taiwanese women.
PMID- 26443346
TI - The Ecology and Evolution of Microbial Defense Systems in Escherichia coli.
AB - Microbes produce an extraordinary array of microbial defense systems. These
include broad-spectrum classical antibiotics critical to human health concerns;
metabolic by-products, such as the lactic acids produced by lactobacilli; lytic
agents, such as lysozymes found in many foods; and numerous types of protein
exotoxins and bacteriocins. The abundance and diversity of this biological
arsenal are clear. Lactic acid production is a defining trait of lactic acid
bacteria. Bacteriocins are found in almost every bacterial species examined to
date, and within a species, tens or even hundreds of different kinds of
bacteriocins are produced. Halobacteria universally produce their own version of
bacteriocins, the halocins. Streptomycetes commonly produce broad-spectrum
antibiotics. It is clear that microbes invest considerable energy in the
production and elaboration of antimicrobial mechanisms. What is less clear is how
such diversity arose and what roles these biological weapons play in microbial
communities. One family of microbial defense systems, the bacteriocins, has
served as a model for exploring evolutionary and ecological questions. In this
review, current knowledge of how the extraordinary range of bacteriocin diversity
arose and is maintained in one species of bacteria, Escherichia coli, is assessed
and the role these toxins play in mediating microbial dynamics is discussed.
PMID- 26443345
TI - Genetics of Glioblastomas in Rare Anatomical Locations: Spinal Cord and Optic
Nerve.
PMID- 26443347
TI - Type 1 Fimbriae, Curli, and Antigen 43: Adhesion, Colonization, and Biofilm
Formation.
AB - This review is primarily concerned with the first step in biofilm formation,
namely, bacterial attachment to surfaces. It describes three examples of
bacterial adhesins, each of which belongs to a different subgroup and follows
different strategies for surface presentation and adhesin exposure. These are
type 1 fimbriae, very long stiff rodlike organelles; curli, amorphous fluffy coat
structures; and finally antigen 43, short outer membrane structures with a simple
assembly system. Their role as adhesins, their structure and biosynthesis, and
their role in biofilm formation are described in detail in the review. The FimH
protein presented by type 1 fimbriae seems to be a highly versatile adhesin
fulfilling a diverse spectrum of roles ranging from pellicle and biofilm
formation to being a bona fide virulence factor in uropathogenic E. coli (UPEC)
strains, where it plays important roles in the manifestation of cystitis. Curli
formation promotes two fundamental processes associated with biofilm formation:
initial adhesion and cell-to-cell aggregation. A role for curli in the
colonization of inert surfaces has been demonstrated. Severe sepsis and septic
shock are frequently caused by gram-negative bacteria, and several factors
suggest a significant role for curli during E. coli sepsis. The protection
provided by Ag43-mediated aggregation was underlined in a series of experiments
addressing the role of Ag43 in protection against oxidizing agents. Type 1
fimbriae, curli, and Ag43 are structurally different bacterial surface structures
and follow completely different strategies for surface display and assembly.
PMID- 26443348
TI - Regulation of Glutamine Synthetase Activity.
AB - Detailed studies of the glutamine synthetase (GS) in Escherichia coli and other
bacteria have shown that the activity of this enzyme is regulated by at least
five different mechanisms: (i) cumulative feedback inhibition by multiple end
products of glutamine metabolism, (ii) interconversion between taut and relaxed
protein configurations in response to binding and dissociation of divalent
cations at one of its two metal binding sites, (iii) dynamic interconversion of
the enzyme between covalently modified (adenylylated) and unmodified forms by a
novel bicyclic cascade system, (iv) repression and derepression of glutamine
synthetase formation by cyclic phosphorylation and dephosphorylation of an RNA
factor that governs transcription activities, and (v) regulation of glutamine
synthetase turnover by the coupling of site specific metal ion-catalyzed
oxidation with proteolytic degradation of the enzyme. Glutamine synthetase
activity in E. coli is subject to inhibition by seven different end products of
glutamine metabolism, namely, by tryptophan, histidine, carbamyl-phosphate, CTP,
AMP, glucose-6-phosphate, and NAD+, and also by serine, alanine, and glycine. The
cascade theory predicts that the steady-state level of glutamine synthetase
adenylylation and therefore its catalytic activity is determined by the combined
effects of all metabolites that affect the kinetic parameters of one or more of
the enzymes in the cascade. Furthermore, under conditions where the supplies of
ATP and glutamate are not limiting and the production of glutamine exceeds the
demand, GS is no longer needed, then it will be converted to the catalytically
inactive adenylylated form that is not under protection of ATP and glutamate.
PMID- 26443349
TI - The Influence of Ecological Factors on the Distribution and the Genetic Structure
of Escherichia coli.
AB - This review focuses on recent data concerning the ecological factors that
determine the distribution of Escherichia coli and the genetic structures of
naturally occurring E. coli populations. It summarizes some of the older
literature concerning the dynamics of E. coli populations within a host and poses
some questions that arise from our more recently acquired understanding of the
factors affecting the genetic structures of E. coli populations. Multilocus
enzyme electrophoresis (MLEE) studies indicate that E. coli, relative to other
members of the family Enterobacteriaceae, exhibits a moderate degree of genetic
diversity. The existence of subspecific structure in E. coli has for the most
part been determined by largely neutral in its effects on the fitness of a
strain. The consequences for E. coli of the transition between its primary and
secondary habitats are of considerable practical significance for water quality
assessment and disease transmission. E. coli causes a significant fraction of
human bacterial disease and is responsible for two main types of disease in
humans and domestic animals: diarrheal disease and extraintestinal infections.
The observed distribution of strains from the different E. coli genetic groups
indicates that they have different life history tactics and ecological niches. A
and B1 strains appear to be generalists, as they can be recovered from any
vertebrate group. Group B2 and D strains appear to be more specialized, as they
are largely restricted to endothermic vertebrates.
PMID- 26443350
TI - Anaerobic Formate and Hydrogen Metabolism.
AB - During fermentative growth, Escherichia coli degrades carbohydrates via the
glycolytic route into two pyruvate molecules. Pyruvate can be reduced to lactate
or nonoxidatively cleaved by pyruvate formate lyase into acetyl-coenzyme A
(acetyl-CoA) and formate. Acetyl-CoA can be utilized for energy conservation in
the phosphotransacetylase (PTA) and acetate kinase (ACK) reaction sequence or can
serve as an acceptor for reducing equivalents gathered during pyruvate formation,
through the action of alcohol dehydrogenase (AdhE). Formic acid is strongly
acidic and has a redox potential of -420 mV under standard conditions and
therefore can be classified as a high-energy compound. Its disproportionation
into CO2 and molecular hydrogen (Em,7 -420 mV) via the formate hydrogenlyase
(FHL) system is therefore of high selective value. The FHL reaction involves the
participation of at least seven proteins, most of which are metalloenzymes, with
requirements for iron, molybdenum, nickel, or selenium. Complex auxiliary systems
incorporate these metals. Reutilization of the hydrogen evolved required the
evolution of H2 oxidation systems, which couple the oxidation process to an
appropriate energy-conserving terminal reductase. E. coli has two hydrogen
oxidizing enzyme systems. Finally, fermentation is the "last resort" of energy
metabolism, since it gives the minimal energy yield when compared with
respiratory processes. Consequently, fermentation is used only when external
electron acceptors are absent. This has necessitated the establishment of
regulatory cascades, which ensure that the metabolic capability is appropriately
adjusted to the physiological condition. Here we review the genetics,
biochemistry, and regulation of hydrogen metabolism and its hydrogenase
maturation system.
PMID- 26443351
TI - Exoribonucleases and Endoribonucleases.
AB - This review provides a description of the known Escherichia coli ribonucleases
(RNases), focusing on their structures, catalytic properties, genes,
physiological roles, and possible regulation. Currently, eight E. coli
exoribonucleases are known. These are RNases II, R, D, T, PH, BN, polynucleotide
phosphorylase (PNPase), and oligoribonuclease (ORNase). Based on sequence
analysis and catalytic properties, the eight exoribonucleases have been grouped
into four families. These are the RNR family, including RNase II and RNase R; the
DEDD family, including RNase D, RNase T, and ORNase; the RBN family, consisting
of RNase BN; and the PDX family, including PNPase and RNase PH. Seven well
characterized endoribonucleases are known in E. coli. These are RNases I, III, P,
E, G, HI, and HII. Homologues to most of these enzymes are also present in
Salmonella. Most of the endoribonucleases cleave RNA in the presence of divalent
cations, producing fragments with 3'-hydroxyl and 5'-phosphate termini. RNase H
selectively hydrolyzes the RNA strand of RNA?DNA hybrids. Members of the RNase H
family are widely distributed among prokaryotic and eukaryotic organisms in three
distinct lineages, RNases HI, HII, and HIII. It is likely that E. coli contains
additional endoribonucleases that have not yet been characterized. First of all,
endonucleolytic activities are needed for certain known processes that cannot be
attributed to any of the known enzymes. Second, homologues of known
endoribonucleases are present in E. coli. Third, endonucleolytic activities have
been observed in cell extracts that have different properties from known enzymes.
PMID- 26443352
TI - Vaccines against Infections Caused by Salmonella, Shigella, and Pathogenic
Escherichia coli.
AB - Infectious diseases represent one of the most common causes of death worldwide,
with the enteropathogenic bacteria Salmonella and Shigella and pathogenic
Escherichia coli being among the most detrimental. Currently, vaccination
represents the preferred method of preventing such infections. For stimulating
the adaptive immune response, immunizations are frequently based on formulations
which include inactivated whole-cell vaccines, live attenuated vaccines, or
subunit vaccines. These can be administered via a parenteral or mucosal route,
the latter having the advantage that it most closely mimics the actual course of
infection. In addition to the type of vaccine and method of application,
important consideration needs to be paid to safety, efficacy, and cost, which are
often major bottlenecks in the successful implementation of vaccines. In this
chapter we take a limited look at the history surrounding vaccinations involving
Salmonella, Shigella, and pathogenic E. coli. Salmonella infections, which can
lead to typhoid fever, are becoming increasing difficult to treat with
antibiotics due to multi-drug-resistant strains. At present, the parenteral Vi
based subunit vaccines and the live attenuated oral vaccine Ty21a have proven to
be the vaccines of choice, with high levels of protective efficacy and limited
side effects. Shigella infections are responsible for the diarrheal disease
shigellosis. Various live and nonliving mucosal and parenteral vaccines have been
tested, with the most promising candidates evolving around those that stimulate
the production of O-antigen-specific antibodies. Pathogenic Escherichia coli
infections can lead to severe diseases due to the bacterium's production of
several specific toxins. Vaccines against this bacterium target its toxins, as
well as surface-exposed antigens, all of which have been found to be effective as
immunogens.
PMID- 26443353
TI - Selenophosphate Synthetase.
AB - Selenophosphate synthetase, the selD gene product from Escherichia coli, is one
of the enzymes required for the synthesis and specific insertion of
selenocysteine into proteins directed by the TGA codon. Selenophosphate
synthetases have been isolated from or are thought to be present in most
organisms; however, the best characterized selenophosphate synthetase is from E.
coli, in which both in vivo and in vitro studies have been performed. Leinfelder
and coworkers showed that an E. coli mutant lacking an intact selD gene fails to
incorporate Se into both the selenocysteine-containing enzyme formate
dehydrogenase (FDH) and tRNA species that normally contain 2-selenouridine
residues at the wobble position. Thus, this study strongly implicated
selenophosphate as playing a major role in E. coli selenium metabolic pathways.
The selenophosphate synthetase reaction requires some form of reduced selenium
such as hydrogen selenide (HSe-) and ATP as substrates to generate a
stoichiometric amount of SePO3, AMP, and orthophosphate. Studies of
selenophosphate inhibition have provided further insight into the mechanism of
selenophosphate synthetase. An assay by which AMP formation is measured in the
absence of selenide showed that selenophosphate synthetase catalyzes hydrolysis
of ATP to AMP and two orthophosphates in an uncoupled reaction. The sequencing of
selenophosphate synthetase genes from various organisms reveals several conserved
regions in the gene product. Recent investigations into the mechanism of
selenophosphate synthetase have revealed a property of selenophosphate synthetase
not previously observed. In samples of purified selenophosphate synthetase, an
unusual optical absorption spectrum is seen.
PMID- 26443354
TI - The Life of Commensal Escherichia coli in the Mammalian Intestine.
AB - In this chapter we review the literature with respect to what is known about how
Escherichia coli colonizesthe mammalian intestine. We begin with a brief
discussion of the mammalian large intestine, the major site that commensal
strains of E. coli colonize. Next, evidence is discussed showing that, in order
to colonize, E. coli must be able to penetrate and grow in the mucus layer of the
large intestine. This is followed by discussions of colonization resistance,
i.e., factors that are involved in the ability of a complete microbiota
(microflora) to resist colonization by an invading bacterium, the advantages and
disadvantages of the in vivo colonization models used in colonization research,
the initiation and maintenance stages of E. coli colonization, and the rate of E.
coli growth in the intestine. The next two sections of the chapter discuss the
role of motility in colonization and how adhesion to mucosal receptors aids or
inhibits penetration of the intestinal mucus layer and thereby either promotes or
prevents E. coli colonization. Finally, the contribution of nutrition to the
ability of E. coli to colonize is discussed based on the surprising finding that
different nutrients are used by E. coli MG1655, a commensal strain, and by E.
coli EDL933, an enterohemorrhagic strain, to colonize the intestine.
PMID- 26443355
TI - Cytotoxic Necrotizing Factors: Rho-Activating Toxins from Escherichia coli.
AB - This article reviews the Escherichia coli toxins called cytotoxic necrotizing
factors (CNFs), which cause activation of Rho GTPases. It describes their modes
of action, structure-function relationships, and roles in disease. Rho GTPases,
the targets of CNFs, belong to the Ras superfamily of low molecular mass GTPases
and act as molecular switches in various signaling pathways. Low molecular mass
GTPases of the Rho family are known as master regulators of the actin
cytoskeleton. Moreover, they are involved in various signal transduction
processes, from transcriptional activation, cell cycle progression, and cell
transformation to apoptosis. CNFs are cytotoxic for a wide variety of cells,
including 3T3 fibroblasts, Chinese hamster ovary cells, Vero cells, HeLa cells,
and cell lines of neuronal origin. This implies that a commonly expressed
receptor is responsible for the uptake of CNF1. Cultured mammalian cells treated
with CNFs are characterized by dramatic changes in actin-containing structures,
including stress fibers, lamellipodia, and filopodia. Most striking is the
formation of multinucleation in these cells. Rho GTPases are increasingly
recognized as essential factors in the development of cancer and metastasis. This
fact has initiated a discussion as to whether activation of Rho proteins by CNFs
might be involved in tumorigenesis. Moreover, CNF1 increases the expression of
the cyclooxygenase 2 (Cox2) gene in fibroblasts. Increased expression of Cox2 is
observed in some types of tumors, e.g., colon carcinoma. Lipid-mediators produced
by the enzyme are suggested to be responsible for tumor progression.
PMID- 26443356
TI - Molecular Epidemiology of Extraintestinal Pathogenic Escherichia coli.
AB - Extraintestinal pathogenic Escherichia coli (ExPEC), the specialized E. coli
strains that possess the ability to overcome or subvert host defenses and cause
extraintestinal disease, are important pathogens in humans and certain animals.
Molecular epidemiological analysis has led to an appreciation of ExPEC as being
distinct from other E. coli (including intestinal pathogenic and commensal
variants) and has offered insights into the ecology, evolution, reservoirs,
transmission pathways, host-pathogen interactions, and pathogenetic mechanisms of
ExPEC. Molecular epidemiological analysis also provides an essential complement
to experimental assessment of virulence mechanisms. This chapter first reviews
the basic conceptual and methodological underpinnings of the molecular
epidemiological approach and then summarizes the main aspects of ExPEC that have
been investigated using this approach.
PMID- 26443357
TI - The Cytology of Bacterial Conjugation.
AB - This review focuses on the membrane-associated structures present at cell-cell
contact sites during bacterial conjugation. These transfer proteins/structures
have roles in the formation and stabilization of mating contacts and ultimately
the passage of substrate across the cell envelope between two bacterial cells.
The review presents evidence for the dynamic interaction between donor and
recipient cells, including the assembly of a transmembrane protein complex, and
concludes with a refined model for the mechanism of bacterial conjugation.
Bacterial conjugation, in addition to being a mechanism for genome evolution, can
be considered as a mechanism for macromolecular secretion. In particular, plasmid
conjugative transfer is classified as a type IV secretion (T4S) system and
represents the only known bacterial system for secretion of DNA. In all known
conjugative transfer systems, a multitude of proteins are required for both
plasmid transfer and pilus production. The plasmids discussed in the review
include the F factor; the P group of plasmids, including RP4 and R751 (rigid);
and the H plasmid group, including R27 (also thick flexible). With the LacI
GFP/lacO system, the F, P, and H plasmids were observed to reside at well-defined
positions located at the mid and quarter-cell positions of Escherichia coli
throughout the vegetative cycle. In this review, recent observations based on
bacterial cell biology techniques, including visualization of plasmid DNA and
proteins at the subcellular level, have been combined with electron and light
microscopy studies of mating cells to create an integrated overview of gram
negative bacterial conjugation, a concept referred to as the conjugative cycle.
PMID- 26443358
TI - Cytokines in Salmonellosis.
AB - The recruitment and activation of phagocytic cells in infected tissues and the
induction of T-cell- and B-cell-dependent acquired immunity are crucial for the
control and resolution of Salmonella infections. These complex processes require
the interaction of bacteria with a multitude of cell surface receptors and the
controlled production of soluble mediators. The mechanisms of cytokine induction
in response to Salmonella and the role of cytokine networks in Salmonella
infections are the main foci of this review. Pathogen-associated molecular
pattern receptors play an important role in recognition of bacteria by the host.
Effective immunity against the bacterium therefore relies on the ability of the
host to recruit phagocytes in the tissues and to enhance the antibacterial
functions of these inflammatory cells. TNF-a, IFN-?, IL12, IL15, and IL18 are
needed for the full expression of innate host resistance to Salmonella. The genes
for mammalian cytokines can be cloned into suitable vectors and expressed in
Salmonella as functional proteins. The in vivo production of cytokines by
Salmonella carriers can have therapeutic applications and can modulate immune
functions in the host. The possibility to modulate antigen-specific immune
responses by expressing cytokines in Salmonella is illustrated by the increase in
Salmonella-specific IgA responses induced by administration of IL-5-expressing
bacteria. The same cytokines that are responsible for endotoxic shock are
elevated in the late stages of lethal Salmonella infections, indicating that the
toxicity of Salmonella lipopolysaccharide (LPS) may actually be contributing to
the death of the host.
PMID- 26443359
TI - Selenocysteine Lyase.
AB - Selenocysteine is a naturally occurring analog of cysteine in which the sulfur
atom of the latter is replaced with selenium. This seleno-amino acid occurs as a
specific component of various selenoproteins and selenium-dependent enzymes.
Incorporation of selenocysteine into these proteins occurs cotranslationally as
directed by the UGA codon. For this process, a special tRNA having an anticodon
complimentary to UGA, tRNASec, is utilized. In Escherichia coli and related
bacteria, this tRNA first is amino acylated with serine, and the seryl-tRNASec is
converted to selenocysteyl-tRNASec. The specific incorporation of selenocysteine
into proteins directed by the UGA codon depends on the synthesis of selenocysteyl
tRNASec. Included in the selenium delivery protein category are rhodaneses that
mobilize selenium from inorganic sources and NIFS-like proteins that liberate
elemental selenium from selenocysteine. The NIFS protein from Azotobacter
vinelandii was found to serve as an efficient catalyst in vitro for delivery of
selenium from free selenocysteine to Escherichia coli selenophosphate synthetase
for selenophosphate formation. The widespread distribution of selenocysteine
lyase in numerous bacterial species was reported and the bacterial enzymes, like
the pig liver enzyme, required pyridoxal phosphate as cofactor. Three NIFS-like
genes were isolated from E. coli by Esaki and coworkers and the expressed gene
products were isolated and characterized. One of these NIFS-like proteins also
exhibited a high preference for selenocysteine over cysteine. M. vannielii, an
anaerobic methane-producing organism, that grows in a mineral medium containing
formate as sole organic carbon source, synthesizes several specific selenoenzymes
required for growth and energy production under these conditions.
PMID- 26443360
TI - Modified Nucleosides of Escherichia coli Ribosomal RNA.
AB - The modified nucleosides of RNA are chemically altered versions of the standard
A, G, U, and C nucleosides. This review reviews the nature and location of the
modified nucleosides of Escherichia coli rRNA, the enzymes that form them, and
their known and/or putative functional role. There are seven Psi (pseudouridines)
synthases to make the 11 pseudouridines in rRNA. There is disparity in numbers
because RluC and RluD each make 3 pseudouridines. Crystal structures have shown
that the Psi synthase domain is a conserved fold found only in all five families
of Psi synthases. The conversion of uridine to Psi has no precedent in known
metabolic reactions. Other enzymes are known to cleave the glycosyl bond but none
carry out rotation of the base and rejoining to the ribose while still enzyme
bound. Ten methyltransferases (MTs) are needed to make all the methylated
nucleosides in 16S RNA, and 14 are needed for 23S RNA. Biochemical studies
indicate that the modes of substrate recognition are idiosyncratic for each Psi
synthase since no common mode of recognition has been detected in studies of the
seven synthases. Eight of the 24 expected MTs have been identified, and six
crystal structures have been determined. Seven of the MTs and five of the
structures are class I MTs with the appropriate protein fold plus unique
appendages for the Psi synthases. The remaining MT, RlmB, has the class IV
trefoil knot fold.
PMID- 26443361
TI - Catabolism of Hexuronides, Hexuronates, Aldonates, and Aldarates.
AB - Following elucidation of the regulation of the lactose operon in Escherichia
coli, studies on the metabolism of many sugars were initiated in the early 1960s.
The catabolic pathways of D-gluconate and of the two hexuronates, D-glucuronate
and D-galacturonate, were investigated. The post genomic era has renewed interest
in the study of these sugar acids and allowed the complete characterization of
the D-gluconate pathway and the discovery of the catabolic pathways for L
idonate, D-glucarate, galactarate, and ketogluconates. Among the various sugar
acids that are utilized as sole carbon and energy sources to support growth of E.
coli, galacturonate, glucuronate, and gluconate were shown to play an important
role in the colonization of the mammalian large intestine. In the case of sugar
acid degradation, the regulators often mediate negative control and are
inactivated by interaction with a specific inducer, which is either the substrate
or an intermediate of the catabolism. These regulators coordinate the synthesis
of all the proteins involved in the same pathway and, in some cases, exert
crosspathway control between related catabolic pathways. This is particularly
well illustrated in the case of hexuronide and hexuronate catabolism. The
structural genes encoding the different steps of hexuronate catabolism were
identified by analysis of numerous mutants affected for growth with galacturonate
or glucuronate. E. coli is able to use the diacid sugars D-glucarate and
galactarate (an achiral compound) as sole carbon source for growth. Pyruvate and
2-phosphoglycerate are the final products of the D-glucarate/galactarate
catabolism.
PMID- 26443362
TI - Virulence Gene Regulation in Shigella.
AB - Shigella species are the causative agents of bacillary dysentery in humans, an
invasive disease in which the bacteria enter the cells of the epithelial layer of
the large intestine, causing extensive tissue damage and inflammation. They rely
on a plasmid-encoded type III secretion system (TTSS) to cause disease; this
system and its regulation have been investigated intensively at the molecular
level for decades. The lessons learned have not only deepened our knowledge of
Shigella biology but also informed in important ways our understanding of the
mechanisms used by other pathogenic bacteria to cause disease and to control
virulence gene expression. In addition, the Shigella story has played a central
role in the development of our appreciation of the contribution of horizontal DNA
transfer to pathogen evolution.A 30-kilobase-pair "Entry Region" of the 230-kb
virulence plasmid lies at the heart of the Shigella pathogenesis system. Here are
located the virB and mxiE regulatory genes and most of the structural genes
involved in the expression of the TTSS and its effector proteins. Expression of
the virulence genes occurs in response to an array of environmental signals,
including temperature, osmolarity, and pH.At the top of the regulatory hierarchy
and lying on the plasmid outside the Entry Region isvirF, encoding an AraC-like
transcription factor.Virulence gene expression is also controlled by chromosomal
genes,such as those encoding the nucleoid-associated proteins H-NS, IHF, and Fis,
the two-component regulators OmpR/EnvZ and CpxR/CpxA, the anaerobic regulator
Fnr, the iron-responsive regulator Fur, and the topoisomerases of the cell that
modulate DNA supercoiling. Small regulatory RNAs,the RNA chaperone Hfq,and
translational modulation also affect the expression of the virulence
phenotypetranscriptionally and/orposttranscriptionally.
PMID- 26443363
TI - Regulation of Serine, Glycine, and One-Carbon Biosynthesis.
AB - The biosynthesis of serine, glycine, and one-carbon (C1) units constitutes a
major metabolic pathway in Escherichia coli and Salmonella enterica serovar
Typhimurium. C1 units derived from serine and glycine are used in the synthesis
of purines, histidine, thymine, pantothenate, and methionine and in the
formylation of the aminoacylated initiator fMet-TRNAfMet used to start
translation in E. coli and serovar Typhimurium. The need for serine, glycine, and
C1 units in many cellular functions makes it necessary for the genes encoding
enzymes for their synthesis to be carefully regulated to meet the changing
demands of the cell for these intermediates. This review discusses the regulation
of the following genes: serA, serB, and serC; gly gene; gcvTHP operon; lpdA; gcvA
and gcvR; and gcvB genes. Threonine utilization (the Tut cycle) constitutes a
secondary pathway for serine and glycine biosynthesis. L-Serine inhibits the
growth of E. coli cells in GM medium, and isoleucine releases this growth
inhibition. The E. coli glycine transport system (Cyc) has been shown to
transport glycine, D-alanine, D-serine, and the antibiotic D-cycloserine.
Transport systems often play roles in the regulation of gene expression, by
transporting effector molecules into the cell, where they are sensed by soluble
or membrane-bound regulatory proteins.
PMID- 26443364
TI - Biosynthesis of Glutamate, Aspartate, Asparagine, L-Alanine, and D-Alanine.
AB - Glutamate, aspartate, asparagine, L-alanine, and D-alanine are derived from
intermediates of central metabolism, mostly the citric acid cycle, in one or two
steps. While the pathways are short, the importance and complexity of the
functions of these amino acids befit their proximity to central metabolism.
Inorganic nitrogen (ammonia) is assimilated into glutamate, which is the major
intracellular nitrogen donor. Glutamate is a precursor for arginine, glutamine,
proline, and the polyamines. Glutamate degradation is also important for survival
in acidic environments, and changes in glutamate concentration accompany changes
in osmolarity. Aspartate is a precursor for asparagine, isoleucine, methionine,
lysine, threonine, pyrimidines, NAD, and pantothenate; a nitrogen donor for
arginine and purine synthesis; and an important metabolic effector controlling
the interconversion of C3 and C4 intermediates and the activity of the DcuS-DcuR
two-component system. Finally, L- and D-alanine are components of the peptide of
peptidoglycan, and L-alanine is an effector of the leucine responsive regulatory
protein and an inhibitor of glutamine synthetase (GS). This review summarizes the
genes and enzymes of glutamate, aspartate, asparagine, L-alanine, and D-alanine
synthesis and the regulators and environmental factors that control the
expression of these genes. Glutamate dehydrogenase (GDH) deficient strains of E.
coli, K. aerogenes, and S. enterica serovar Typhimurium grow normally in glucose
containing (energy-rich) minimal medium but are at a competitive disadvantage in
energy limited medium. Glutamate, aspartate, asparagine, L-alanine, and D-alanine
have multiple transport systems.
PMID- 26443365
TI - Evolution and Ecology of Salmonella.
AB - Over the past 120 to 160 million years, the genus Salmonella has evolved into a
complex group of more than 2,300 genetically and phenotypically diverse serovars.
Members of this genus are able to infect a wide diversity of vertebrate and
invertebrate hosts; disease manifestations in humans range from gastroenteritis
to typhoid fever. The evolution of the genus Salmonella and the divergence and
radiation of particular lineages within this group have resulted from selection
acting on new genetic variation generated by events such as the gain, loss,
and/or rearrangement of genetic material. These types of genetic events have
contributed to the speciation of Salmonella from its ancestral association with
cold-blood animals to a pathogen of warm-blooded hosts. Moreover, adaptive
radiation due to changes in gene content within S. enterica subspecies I has
impacted host specificity and aided in the selection of host-restricted, host
adapted, and non-host-adapted serovars. In addition to the genetic diversity
important for the wide phenotypic heterogeneity within the genus, a subset of
core Salmonella-specific genes present in all Salmonella species and serovars has
been identified that may contribute to the conserved aspects of the lifestyle of
this microorganism, including the ability to survive in nutrient-poor nonhost
environments such as soil and water. Whole-genome comparisons of isolates
differing in host range and virulence will continue to elucidate the genetic
mechanisms that have contributed to the evolution and diverse ecology of the
genus Salmonella.
PMID- 26443366
TI - Biosynthesis of Arginine and Polyamines.
AB - Early investigations on arginine biosynthesis brought to light basic features of
metabolic regulation. The most significant advances of the last 10 to 15 years
concern the arginine repressor, its structure and mode of action in both E. coli
and Salmonella typhimurium, the sequence analysis of all arg structural genes in
E. coli and Salmonella typhimurium, the resulting evolutionary inferences, and
the dual regulation of the carAB operon. This review provides an overall picture
of the pathways, their interconnections, the regulatory circuits involved, and
the resulting interferences between arginine and polyamine biosynthesis.
Carbamoylphosphate is a precursor common to arginine and the pyrimidines. In both
Escherichia coli and Salmonella enterica serovar Typhimurium, it is produced by a
single synthetase, carbamoylphosphate synthetase (CPSase), with glutamine as the
physiological amino group donor. This situation contrasts with the existence of
separate enzymes specific for arginine and pyrimidine biosynthesis in Bacillus
subtilis and fungi. Polyamine biosynthesis has been particularly well studied in
E. coli, and the cognate genes have been identified in the Salmonella genome as
well, including those involved in transport functions. The review summarizes what
is known about the enzymes involved in the arginine pathway of E. coli and S.
enterica serovar Typhimurium; homologous genes were identified in both organisms,
except argF (encoding a supplementary OTCase), which is lacking in Salmonella.
Several examples of putative enzyme recruitment (homologous enzymes performing
analogous functions) are also presented.
PMID- 26443367
TI - C4-Dicarboxylate Degradation in Aerobic and Anaerobic Growth.
AB - C4-dicarboxylates, like succinate, fumarate, L- and D-malate, tartrate, and the
C4-dicarboxylic amino acid aspartate, support aerobic and anaerobic growth of
Escherichia coli and related bacteria and can serve as carbon and energy sources.
In aerobic growth, the C4-dicarboxylates are oxidized in the citric acid cycle.
Due to the interruption of the citric acid cycle under anaerobic conditions,
anaerobic metabolism of the C4-dicarboxylates depends on fumarate reduction to
succinate. In some related bacteria (e.g., Klebsiella), degradation of C4
dicarboxylates, like tartrate, uses a different mechanism and pathway. It
requires the functioning of an Na+-dependent and membrane-associated oxaloacetate
decarboxylase. Due to the incomplete function of the citric acid cycle in
anaerobic growth, succinate supports only aerobic growth of E. coli. This chapter
describes the pathways of and differences in aerobic and anaerobic C4
dicarboxylate metabolism and the physiological consequences. The citric acid
cycle, fumarate respiration, and fumarate reductase are discussed here only in
the context of aerobic and anaerobic C4-dicarboxylate metabolism. Some recent
aspects of C4-dicarboxylate metabolism, such as transport and sensing of C4
dicarboxylates, and their relationships are treated in more detail.
PMID- 26443368
TI - Fermentative Pyruvate and Acetyl-Coenzyme A Metabolism.
AB - Pyruvate and acetyl-CoA form the backbone of central metabolism. The nonoxidative
cleavage of pyruvate to acetyl-CoA and formate by the glycyl radical enzyme
pyruvate formate lyase is one of the signature reactions of mixed-acid
fermentation in enterobacteria. Under these conditions, formic acid accounts for
up to one-third of the carbon derived from glucose. The further metabolism of
acetyl-CoA to acetate via acetyl-phosphate catalyzed by phosphotransacetylase and
acetate kinase is an exemplar of substrate-level phosphorylation. Acetyl-CoA can
also be used as an acceptor of the reducing equivalents generated during
glycolysis, whereby ethanol is formed by the polymeric acetaldehyde/alcohol
dehydrogenase (AdhE) enzyme. The metabolism of acetyl-CoA via either the acetate
or the ethanol branches is governed by the cellular demand for ATP and the
necessity to reoxidize NADH. Consequently, in the absence of an electron acceptor
mutants lacking either branch of acetyl-CoA metabolism fail to cleave pyruvate,
despite the presence of PFL, and instead reduce it to D-lactate by the D-lactate
dehydrogenase. The conversion of PFL to the active, radical-bearing species is
controlled by a radical-SAM enzyme, PFL-activase. All of these reactions are
regulated in response to the prevalent cellular NADH:NAD+ ratio. In contrast to
Escherichia coli and Salmonella species, some genera of enterobacteria, e.g.,
Klebsiella and Enterobacter, produce the more neutral product 2,3-butanediol and
considerable amounts of CO2 as fermentation products. In these bacteria, two
molecules of pyruvate are converted to alpha-acetolactate (AL) by alpha
acetolactate synthase (ALS). AL is then decarboxylated and subsequently reduced
to the product 2,3-butandiol.
PMID- 26443369
TI - Escherichia coli and Salmonella 2000: the View From Here.
AB - In 1995, an editorial in Science (267:1575) commented that predictions made some
25 years previously regarding "Biology and the Future of Man" were largely
fulfilled but that "the most revolutionary and unexpected findings were not
predicted." We would be glad to do as well! As we stated at the beginning, our
work as editors of the Escherichia coli and Salmonella book did not endow us with
special powers of prophecy but it does permit us to express our excitement for
the future. In our opinion, E. coli and S. enterica will continue to play a
central role in biological research. This is not because they are intrinsically
more interesting than any other bacteria, as we believe that all bacteria are
equally interesting. However, knowledge builds on knowledge, and it is here that
these two species continue to have a large edge not only over other
microorganisms but also, for some time to come, over all other forms of life. It
is interesting in this connection that biotechnology, having made detours through
other microorganisms, always seems to return to E. coli.
PMID- 26443370
TI - Molecular Basis for Bacterial Growth on Citrate or Malonate.
AB - Environmental citrate or malonate is degraded by a variety of aerobic or
anaerobic bacteria. For selected examples, the genes encoding the specific
enzymes of the degradation pathway are described together with the encoded
proteins and their catalytic mechanisms. Aerobic bacteria degrade citrate readily
by the basic enzyme equipment of the cell if a specific transporter for citrate
is available. Anaerobic degradation of citrate in Klebsiella pneumoniae requires
the so-called substrate activation module to convert citrate into its thioester
with the phosphoribosyl dephospho-CoA prosthetic group of citrate lyase. The
citryl thioester is subsequently cleaved into oxaloacetate and the acetyl
thioester, from which a new citryl thioester is formed as the turnover continues.
The degradation of malonate likewise includes a substrate activation module with
a phosphoribosyl dephospho-CoA prosthetic group. The machinery gets ready for
turnover after forming the acetyl thioester with the prosthetic group. The acetyl
residue is then exchanged by a malonyl residue, which is easily decarboxylated
with the regeneration of the acetyl thioester. This equipment suffices for
aerobic growth on malonate, since ATP is produced via the oxidation of acetate.
Anaerobic growth on citrate or malonate, however, depends on additional enzymes
of a so-called energy conservation module. This allows the conversion of
decarboxylation energy into an electrochemical gradient of Na+ ions. In citrate
fermenting K. pneumoniae, the Na+ gradient is formed by the oxaloacetate
decarboxylase and mainly used to drive the active transport of citrate into the
cell. To use this energy source for this purpose is possible, since ATP is
generated by substrate phosphorylation in the well-known sequence from pyruvate
to acetate. In the malonate-fermenting bacterium Malonomonas rubra, however, no
reactions for substrate level phosphorylation are available and the Na+ gradient
formed in the malonate decarboxylation reaction must therefore be used as the
driving force for ATP synthesis.
PMID- 26443371
TI - Ammonia Transport.
AB - This review reviews the ammonium/methylammonium transport (Amt) proteins of
Escherichia coli and Salmonella enterica serovar Typhimurium. The Amt proteins
and their homologs, the methylammonium/ammonium permease proteins of
Saccharomyces cerevisiae, constitute a distinct class of membrane-associated
ammonia transporters. Members of the Amt family are found in archaea, bacteria,
fungi, plants, and invertebrate animals. In E. coli and serovar Typhimurium, the
Amt proteins are essential to maintain maximal growth at low concentrations of
ammonia, the preferred nitrogen source. Soupene and coworkers showed that a
mutant of E. coli with only the low-affinity glutamate dehydrogenase pathway for
assimilation of ammonia, which therefore grows slowly at low ammonia
concentrations, is not relieved of its growth defect by overexpression of AmtB. A
recent study on an Amt protein from tomato concluded that it was a specific
transporter for NH4+. A trimeric stoichiometry for AmtB is supported by the
observation of a direct interaction between AmtB and the trimeric signal
transduction protein GlnK. In E. coli, GlnK has been observed to associate with
the membrane in an AmtB-dependent fashion. Both GlnK and GlnB are sensors of
nitrogen status. Their interaction with AmtB suggests a role for AmtB in nitrogen
regulation. In summary, AmtB is a membrane-associated ammonia transporter that is
important for growth at external concentrations of the uncharged species (NH3)
below about 50 nM. The preponderance of evidence suggests that AmtB specifically
transports the charged species (NH4+) and that this transport is passive and,
hence, bidirectional.
PMID- 26443372
TI - Selenocysteine.
AB - About 50 years ago, research on the biological function of the element selenium
was initiated by the report of J. Pinsent that generation of formate
dehydrogenase activity by Escherichia coli requires the presence of both selenite
and molybdate in the growth medium. In nature, selenium is predominantly
associated with sulfur minerals, the Se/S ratios of which vary widely depending
on the geological formation. Because of the chemical similarity between the two
elements, selenium can intrude into the sulfur pathway at high Se/S ratios and
can be statistically incorporated into polypeptides. The central macromolecule
for the synthesis and incorporation of selenocysteine is a specialized tRNA,
designated tRNASec. It is the product of the selC (previously fdhC) gene. tRNASec
fulfils a multitude of functions, which are based on its unique structural
properties, compared to canonical elongator RNAs. tRNASec possesses the
discriminator base G73 and the identity elements of serine-specific tRNA
isoacceptors. The conversion of seryl-tRNASec into selenocysteyl-tRNASec is
catalyzed by selenocysteine synthase, the product of the selA gene (previously
the fdhA locus, which was later shown to harbor two genes, selA and selB). The
crucial element for the regulation is a putative secondary structure at the 5'
end of the untranslated region of the selAB mRNA. The generation and analysis of
transcriptional and translational reporter gene fusions of selA and selB yield an
expression pattern identical to that obtained by measuring the actual amounts of
SelA and SelB proteins.
PMID- 26443373
TI - Different risk factors for bleeding and discontinuation between dabigatran and
rivaroxaban.
AB - BACKGROUND: It is unclear whether risk factors for bleeding and discontinuation
are different between dabigatran and rivaroxaban. METHODS AND RESULTS: We
enrolled consecutive patients with atrial fibrillation who received dabigatran or
rivaroxaban, had a CHADS2 score >1 and creatinine clearance >30ml/min. During
this period, only dabigatran and rivaroxaban were available as non-vitamin K oral
anticoagulants (NOACs) in our hospital. We compared the clinical and demographic
data and the incidence of bleeding for one year between dabigatran group and
rivaroxaban group. As a result, the dabigatran group consisted of 177 patients
and the rivaroxaban group consisted of 179 patients. The incidence of
discontinuation was significantly higher in the dabigatran group than in the
rivaroxaban group (27.7% vs. 13.4%, p<0.001). Multivariate analysis, even after
propensity score-matching analysis, revealed that there were no independent risk
factors for bleeding in the dabigatran group, while in the rivaroxaban group, use
of antiplatelet therapy was an independent factor correlating with bleeding.
CONCLUSIONS: The risk factors for bleeding may be different between dabigatran
and rivaroxaban. To avoid bleeding, rivaroxaban should be prescribed with caution
or avoided in patients using antiplatelet therapy. Upon discontinuation,
rivaroxaban may be more favorable than dabigatran.
PMID- 26443374
TI - Whole exome sequencing combined with integrated variant annotation prediction
identifies a causative myosin essential light chain variant in hypertrophic
cardiomyopathy.
AB - BACKGROUND: The development of candidate gene approaches to enable molecular
diagnosis of hypertrophic cardiomyopathy (HCM) has required extensive and
prolonged efforts. Whole exome sequencing (WES) technologies have already
accelerated genetic studies of Mendelian disorders, yielding approximately 30%
diagnostic success. As a result, there is great interest in extending the use of
WES to any of Mendelian diseases. This study investigated the potential of WES
for molecular diagnosis of HCM. METHODS: WES was performed on seven relatives
from a large HCM family with a clear HCM phenotype (five clinically affected and
two unaffected) in the Kanazawa University Hypertrophic Cardiomyopathy Registry.
Serial bioinformatics filtering methods as well as using combined annotation
dependent depletion (CADD) score and high heart expression (HHE) gene data were
applied to detect the causative variant. Moreover, additional carriers of the
variant were investigated in the HCM registry, and clinical characteristics
harboring the variant were collected and evaluated. RESULTS: WES detected 60020
rare variants in the large HCM family. Of those, 3439 were missense, nonsense,
splice-site, or frameshift variants. After genotype-phenotype matching, 13
putative variants remained. Using CADD score and HHE gene data, the number of
candidates was reduced to one, a variant in the myosin essential light chain
(MYL3, NM_000258.2:c.281G>A, p.Arg94His) that was shared by the five affected
subjects. Additional screening of the HCM registry (n=600) identified two more
subjects with this variant. Serial assessments of the variant carriers revealed
the following phenotypic characteristics: (1) disease-penetrance of 88%; (2) all
clinically affected carriers exhibited asymmetric septal hypertrophy with a
substantial maximum left ventricular wall thickness of 18+/-3mm without any
obstruction. CONCLUSIONS: WES combined with CADD score and HHE gene data may be
useful even in HCM. Furthermore, the MYL3 Arg94His variant was associated with
high disease penetrance and substantial interventricular septal hypertrophy.
PMID- 26443376
TI - Rice ONAC106 Inhibits Leaf Senescence and Increases Salt Tolerance and Tiller
Angle.
AB - NAM/ATAF1/ATAF2/CUC2 (NAC) is a plant-specific transcription factor (TF) family,
and NACs participate in many diverse processes during the plant life cycle.
Several Arabidopsis thaliana NACs have important roles in positively or
negatively regulating leaf senescence, but in other plant species, including
rice, the senescence-associated NACs (senNACs) remain largely unknown. Here we
show that the rice senNAC TF ONAC106 negatively regulates leaf senescence. Leaves
of onac106-1D (insertion of the 35S enhancer in the promoter region of the
ONAC106 gene) mutants retained their green color under natural senescence and
dark-induced senescence conditions. Genome-wide transcriptome analysis revealed
that key senescence-associated genes (SGR, NYC1, OsNAC5, OsNAP, OsEIN3 and OsS3H)
were differentially expressed in onac106-1D during dark-induced senescence. In
addition to delayed senescence, onac106-1D also showed a salt stress-tolerant
phenotype; key genes that down-regulate salt response signaling (OsNAC5,
OsDREB2A, OsLEA3 and OsbZIP23) were rapidly up-regulated in onac106-1D under salt
stress. Interestingly, onac106-1D also exhibited a wide tiller angle phenotype
throughout development, and the tiller angle-related gene LPA1 was down-regulated
in onac106-1D. Using yeast one-hybrid assays, we found that ONAC106 binds to the
promoter regions of SGR, NYC1, OsNAC5 and LPA1. Taking these results together, we
propose that ONAC106 functions in leaf senescence, salt stress tolerance and
plant architecture by modulating the expression of its target genes that function
in each signaling pathway.
PMID- 26443375
TI - Arabidopsis ABA-Activated Kinase MAPKKK18 is Regulated by Protein Phosphatase 2C
ABI1 and the Ubiquitin-Proteasome Pathway.
AB - Phosphorylation and dephosphorylation events play an important role in the
transmission of the ABA signal. Although SnRK2 [sucrose non-fermenting1-related
kinase2] protein kinases and group A protein phosphatase type 2C (PP2C)-type
phosphatases constitute the core ABA pathway, mitogen-activated protein kinase
(MAPK) pathways are also involved in plant response to ABA. However, little is
known about the interplay between MAPKs and PP2Cs or SnRK2 in the regulation of
ABA pathways. In this study, an effort was made to elucidate the role of MAP
kinase kinase kinase18 (MKKK18) in relation to ABA signaling and response. The
MKKK18 knockout lines showed more vigorous root growth, decreased abaxial
stomatal index and increased stomatal aperture under normal growth conditions,
compared with the control wild-type Columbia line. In addition to transcriptional
regulation of the MKKK18 promoter by ABA, we demonstrated using in vitro and in
vivo kinase assays that the kinase activity of MKKK18 was regulated by ABA.
Analysis of the cellular localization of MKKK18 showed that the active kinase was
targeted specifically to the nucleus. Notably, we identified abscisic acid
insensitive 1 (ABI1) PP2C as a MKKK18-interacting protein, and demonstrated that
ABI1 inhibited its activity. Using a cell-free degradation assay, we also
established that MKKK18 was unstable and was degraded by the proteasome pathway.
The rate of MKKK18 degradation was delayed in the ABI1 knockout line. Overall, we
provide evidence that ABI1 regulates the activity and promotes proteasomal
degradation of MKKK18.
PMID- 26443377
TI - The Relationships between Development and Low Temperature Tolerance in Barley
Near Isogenic Lines Differing for Flowering Behavior.
AB - Flowering time, vernalization requirement, photoperiod sensitivity and low
temperature tolerance are key traits in the Triticeae. We characterized a set of
isogenic genetic stocks-representing single and pairwise substitutions of spring
alleles at the VRN-H1, VRN-H2 and VRN-H3 loci in a winter barley background-at
the structural, functional and phenotypic levels. High density mapping with
reference to the barley genome sequence confirmed that in all cases target VRN
alleles were present in the near isogenic lines (NILs) and allowed estimates of
introgression size (at the genetic and physical levels) and gene content.
Expression data corroborated the structural and phenotypic results. The latter
confirmed that substitution of a spring allele at any of the VRN loci is
sufficient to eliminate vernalization requirement. There was no significant
change in low temperature tolerance with substitution of a spring allele at VRN
H2, but there were significant losses in cold tolerance with substitutions at VRN
H1 and VRN-H3. Reductions in cold tolerance are ascribed to an accelerated
transition from the vegetative to reproductive state. The set of NILs will be a
rich resource for understanding the genetics of vernalization, low temperature
tolerance and other traits encoded/regulated by genes within the introgressed
intervals.
PMID- 26443378
TI - A Functional EXXEK Motif is Essential for Proton Coupling and Active
Glucosinolate Transport by NPF2.11.
AB - The proton-dependent oligopeptide transporter (POT/PTR) family shares a highly
conserved E1X1X2E2RFXYY (E1X1X2E2R) motif across all kingdoms of life. This motif
is suggested to have a role in proton coupling and active transport in bacterial
homologs. For the plant POT/PTR family, also known as the NRT1/PTR family (NPF),
little is known about the role of the E1X1X2E2R motif. Moreover, nothing is known
about the role of the X1 and X2 residues within the E1X1X2E2R motif. We used
NPF2.11-a proton-coupled glucosinolate (GLS) symporter from Arabidopsis thaliana
to investigate the role of the E1X1X2E2K motif variant in a plant NPF
transporter. Using liquid chromatography-mass spectrometry (LC-MS)-based uptake
assays and two-electrode voltage clamp (TEVC) electrophysiology, we demonstrate
an essential role for the E1X1X2E2K motif for accumulation of substrate by
NPF2.11. Our data suggest that the highly conserved E1, E2 and K residues are
involved in translocation of protons, as has been proposed for the E1X1X2E2R
motif in bacteria. Furthermore, we show that the two residues X1 and X2 in the
E1X1X2E2[K/R] motif are conserved as uncharged amino acids in POT/PTRs from
bacteria to mammals and that introducing a positive or negative charge in either
position hampers the ability to overaccumulate substrate relative to the assay
medium. We hypothesize that introducing a charge at X1 and X2 interferes with the
function of the conserved glutamate and lysine residues of the E1X1X2E2K motif
and affects the mechanism behind proton coupling.
PMID- 26443380
TI - Acculturation and Psychological Adjustment of Vietnamese Refugees: An Ecological
Acculturation Framework.
AB - Acculturation to the culture of the host society as well as to one's heritage
culture have been shown to impact immigrants' adjustment during the years
following resettlement. While acculturation has been identified as an important
factor in adjustment of Vietnamese immigrants (Birman and Tran in Am J
Orthopsychiatr 78(1):109-120. doi: 10.1037/0002-9432.78.1.109 , 2008), no clear
pattern of findings has emerged and too few studies have employed an ecological
approach. The purpose of this paper is to contextualize the study of
acculturation and adjustment by taking an ecological approach to exploring these
relationships across several life domains, using a bilinear scale, and examining
mediators of these relationships for adult Vietnamese refugees (N = 203) in the
United States. We call this approach the Ecological Acculturation Framework
(EAF). Results of a structural equation model (SEM) showed that job satisfaction
fully mediated the relationship between American acculturation and psychological
distress, demonstrating that this relationship was specific to an occupational
domain. However, while Vietnamese acculturation predicted co-ethnic social
support satisfaction, it did not predict reduced psychological distress.
Implications for a life domains approach, including domain specificity, are
discussed.
PMID- 26443379
TI - Functional analyses of phosphorylation events in human Argonaute 2.
AB - Argonaute 2 (Ago2) protein is a central effector of RNA interference (RNAi)
pathways and regulates mammalian genes on a global level. The mechanisms of Ago2
mediated silencing are well understood, but less is known about its regulation.
Recent reports indicate that phosphorylation significantly affects Ago2 activity.
Here, we investigated the effect of mutating all known phospho-residues within
Ago2 on its localization and activity. Ago2 associates with two different
cytoplasmic RNA granules known as processing bodies (P-bodies) and stress
granules, but the nature of this phenomenon is controversial. We report that
replacing serine with a phospho-mimetic aspartic acid at position 798 completely
abrogates association of Ago2 with P-bodies and stress granules. The effect of
this mutation on its activity in gene silencing was modest, which was surprising
because association of Ago2 with cytoplasmic RNA granules is thought to be a
consequence of its role in RNAi. As such, our data indicate that targeting of
Ago2 to P-bodies and stress granules is separable from its role in RNAi and
likely requires dynamic phosphorylation of serine 798.
PMID- 26443381
TI - Giant photovoltaic effect of ferroelectric domain walls in perovskite single
crystals.
AB - The photovoltaic (PV) effect in polar materials offers great potential for light
energy conversion that generates a voltage beyond the bandgap limit of present
semiconductor-based solar cells. Ferroelectrics have received renewed attention
because of the ability to deliver a high voltage in the presence of ferroelastic
domain walls (DWs). In recent years, there has been considerable debate over the
impact of the DWs on the PV effects, owing to lack of information on the bulk PV
tensor of host ferroelectrics. In this article, we provide the first direct
evidence of an unusually large PV response induced by ferroelastic DWs-termed
'DW'-PV effect. The precise estimation of the bulk PV tensor in single crystals
of barium titanate enables us to quantify the giant PV effect driven by 90
degrees DWs. We show that the DW-PV effect arises from an effective electric
field consisting of a potential step and a local PV component in the 90 degrees
DW region. This work offers a starting point for further investigation into the
DW-PV effect of alternative systems and opens a reliable route for enhancing the
PV properties in ferroelectrics based on the engineering of domain structures in
either bulk or thin-film form.
PMID- 26443382
TI - [Long-term efficacy of Fadenoperation associated to conventional surgery in the
treatment of esotropia with distance-near incomitance: About 55 cases].
AB - OBJECTIVE: The purpose of this study is to evaluate the short-, medium- and long
term efficacy of posterior fixation sutures with conventional surgery in
controlling strabismus in the case of esotropia with distance-near incomitance.
MATERIALS AND METHODS: This is a retrospective study of consecutive patients with
partially accommodative and non-accommodative esotropia associated with distance
near incomitance who underwent posterior fixation sutures along with conventional
surgery. The preoperative and postoperative distance and near deviation
measurements and the distance-near incomitance were evaluated at 1, 6 and 12
years. Surgical success was defined as a postoperative distance angle and a
distance-near incomitance less than 10 prism diopters (PD). RESULTS: In total, 55
patients were included. Preoperatively, the mean distance deviation, near
deviation and distance-near incomitance were 15.9 (+/- 3.4), 29.7 (+/- 5.8) and
13.8 (+/- 3.1) PD, respectively. Postoperatively, the mean distance deviation was
1.6 (+/- 0.8) PD (P < 0.001) at 1 year, 2.8 (+/- 1.6) PD (P< 0.005) at 6 years
and 5.6 (+/- 2.4) PD (P < 0.05) at 12 years. The mean near deviation was 7.8 (+/-
2.3) PD (P < 0.001) at 1 year, 10.5 (+/- 3.7) PD (P < 0.005) at 6 years and 15.2
(+/- 4.4) PD (P < 0.05) at 12 years. The mean distance-near incomitance was 5.2
(+/- 1.8) PD (P < 0.01) at 1 year, 7.7 (+/- 2.8) PD (P < 0.05) at 6 years and 9.6
(+/- 3.2) PD (P > 0.05) at 12 years. The success rate was 91, 78 and 58% at 1, 6
and 12 years, respectively. CONCLUSION: Distance-near incomitance is a source of
amblyopia. It needs to be corrected while treating an esotropia. This study seems
to confirm the short- and medium-term efficacy of posterior fixation sutures
along with conventional surgery in the treatment of this problem. It also seems
to show progressive, albeit partial, loss of its long-term efficacy.
PMID- 26443383
TI - [Clinical pilot study to evaluate the efficacy of a preservative-free hypertonic
ophthalmic solution for patients with symptomatic corneal edema].
AB - This exploratory clinical trial aims to assess the effect on visual acuity and
central corneal thickness of an unpreserved hypertonic ophthalmic solution
containing sodium chloride (5%) and sodium hyaluronate, in patients with chronic
corneal edema caused by endothelial disease reducing their visual acuity. Twenty
patients were enrolled and treated with the hypertonic solution (1 to 2 drops per
eye, 4 times a day over 28 days). Progression of visual acuity (ETDRS score) and
corneal thickness (ultrasonic pachymetry) was measured from baseline (without
treatment) through the treatment period (Day 7 and Day 28). The analyses were
performed on 18 patients (Full Analysis Set [FAS] population). The causes of
corneal edema were Fuchs endothelial dystrophy in 10 cases and post-cataract
surgery endothelial decompensation in 8 patients. The mean visual acuity values
for the FAS population compared between baseline (Day-7) and one week of
treatment (Day+7) show a significant 5-point VA improvement (P<0.001 paired
Wilcoxon test). For corneal thickness, there was also a significant decrease
(P=0.033 paired Wilcoxon test). Functional improvement was observed at 28 days of
instillation. No adverse events were recorded during the clinical study. In
conclusion, the unpreserved hyperosmolar solution containing sodium chloride and
sodium hyaluronate significantly improved ETDRS visual acuity after one week of
use. In this clinical trial, the solution also showed excellent tolerability
results.
PMID- 26443384
TI - The role of miRNAs in endometrial cancer.
AB - miRNAs are small noncoding RNAs that regulate gene expression at the post
transcriptional level. Since their discovery, miRNAs have been associated with
every cell function including malignant transformation and metastasis.
Endometrial cancer is the most common gynecologic malignancy. However,
improvement should be made in interobserver agreement on histological typing and
individualized therapeutic approaches. This article summarizes the role of miRNAs
in endometrial cancer pathogenesis and treatment.
PMID- 26443385
TI - Fluctuating asymmetry as a pollution monitor: The Australian estuarine smooth
toadfish Tetractenos glaber (Teleostei: Tetraodontidae).
AB - The relationship between pollution level in estuarine sediment and fluctuating
asymmetry (FA) of resident smooth toadfish Tetractenos glaber was evaluated. A
total of 188 fish from Sydney and Hawkesbury River estuaries (5 locations from
each) were analysed for 28 bilateral skull bone characters. Sediment pollution
was quantified based on analysis of heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) and
organochlorine pesticides (DDT, DDD, DDE, chlordane, dieldrin, lindane). Sediment
toxicity was characterized using the mean quotient approach (MERMQ) and ranged
from low to moderate level for heavy metals and from low to severe for
organochlorides. The mean shape and directional asymmetry of fish bones differed
among locations, suggesting a response to local environments. FA was positively
correlated with organochlorine pesticides across locations, but not with heavy
metals. These results suggest that fish FA could be a useful estimator of stress
caused by organic toxicity based on the MERMQ approach.
PMID- 26443386
TI - Declines in TBT contamination in Irish coastal waters 1987-2011, using the
dogwhelk (Nucella lapillus) as a biological indicator.
AB - Using the vas deferens sequence index (VDSI) and relative penis size index (RPSI)
in dogwhelks (Nucella lapillus), imposex levels were assessed at 63 sites within
11 sea inlets during 2010/2011 and compared these with levels gathered since
1987. Sterile females (VDS>5.0) were found at 14 of the 63 sites and 47 sites
(75%) met the EcoQO (VDSI<2.0). The absence of imposex in 'control' areas on the
west coast is due to the lack of vessel paint applications or net dips with TBT
being used as an active anti-fouling ingredient. A significant decline was
observed following 2005 when comparing VDSI levels which is consistent with the
decline of TBT usage. Current levels are consistent with an overall improvement
towards achieving Good Environmental Status according to the requirements under
the Marine Strategy Framework Directive.
PMID- 26443387
TI - Impact of deep-water fish farms on benthic macrofauna communities under different
hydrodynamic conditions.
AB - In this study the environmental impacts of two fish farms located over deep water
(180-190 m) were compared. MC-Farm was located at a site with slightly higher
water currents (mean current speed 3-5 cms(-1)) than LC-farm (<2 cms(-1)).
Macrofauna composition, bioirrigation and benthic fluxes (CO2 and NH4(+)) were
quantified at different stages of the production cycle, revealing very different
impact of the two farms. Macrofauna abundance and bioirrigation were stimulated
compared to a non-impacted reference site at MC-farm, while macrofauna diversity
was only moderately reduced. In contrast, macrofauna communities and related
parameters were severely impoverished at LC-Farm. This study suggests that deep
water fish farms should not be sited in low current areas (<2 cms(-1)), since
this will hamper waste dispersal and aggravate environmental impacts. On the
other hand, fish farming at slightly more dynamic sites can lead to stimulated
benthic macrofauna communities and only moderate environmental impacts.
PMID- 26443388
TI - Urinary tract infection-like symptom is associated with worse bladder cancer
outcomes in the Medicare population: Implications for sex disparities.
AB - OBJECTIVES: To determine the time to bladder cancer diagnosis from initial
infection-like symptoms and its impact on cancer outcomes. METHODS: Using
Surveillance, Epidemiology and End Results-Medicare, we designed a retrospective
cohort study identifying beneficiaries aged >= 66 years diagnosed with bladder
cancer from 2007 to 2009. Patients were required to have a hematuria or urinary
tract infection claim within 1 year of bladder cancer diagnosis (n = 21 216), and
have 2 years of prior Medicare data (n = 18 956) without any precedent hematuria,
bladder cancer or urinary tract infection claims (n = 12 195). The number of days
to bladder cancer diagnosis was measured, as well as the impact of sex and
presenting symptom on time to diagnosis, pathology, and oncological outcomes.
RESULTS: The mean time to bladder cancer diagnosis was 72.2 days in women versus
58.9 days in men (P < 0.001). A logistic regression model identified the greatest
predictors of >= pT2 pathology were both women (odds ratio 2.08, 95% confidence
interval 1.70-2.55) and men (odds ratio 1.71, 95% confidence interval 1.49-1.97)
presenting with urinary tract infection. Cox proportional hazards analysis
identified an increased risk of mortality from bladder cancer and all causes in
women presenting with urinary tract infection (hazard ratio 1.37, 95% confidence
interval 1.10-1.71, and hazard ratio 1.47, 95% confidence interval 1.28-1.69)
compared with women with hematuria. CONCLUSIONS: Women have a longer interval
from urinary tract infection to diagnosis of bladder cancer. Urinary tract
infection presentation can adversely affect time to diagnosis, pathology and
survival. Time to diagnosis seems not to be an independent predictor of bladder
cancer outcomes.
PMID- 26443389
TI - Effect of Hyaluronidase Addition to Lidocaine for Trigger Point Injection in
Myofascial Pain Syndrome.
AB - INTRODUCTION: This randomized, double-blind study compared the efficacy of
hyaluronidase co-injection with that of local anesthesia alone on the degree of
pain and quality of life in patients with myofascial pain syndrome (MPS).
METHODS: Sixty-one adults, aged 25 to 75 years, with MPS affecting both trapezius
muscles were randomly assigned to one of the 2 treatment groups: lidocaine (group
L: n = 31) or hyaluronidase (group H: n = 30). All patients received Trigger
point injection (TPI). Group L received 3.2 mL 0.5% lidocaine alone. Group H
received the same solution of lidocaine mixed with hyaluronidase (600 iu/mL).
Patients were followed for 14 days (pre- and post-TPI days 0, 1, 4, 7, and 14)
with the verbal numerical rating scale (VNRS), and the primary outcome was VNRS
on day 7. Also, we evaluated the neck disability index (NDI) and the short form
of brief pain inventory (BPI-SF) on pre- and post-TPI day 14. RESULTS: In both
groups, VNRS decreased on days 4, 7, and 14 compared to the pre-TPI. However, in
group H, VNRS decreased on day 1 also. There were no significant differences of
VNRS between the 2 groups during 14 days. NDI and BPI-SF scores also
significantly decreased after TPI in both groups. CONCLUSIONS: There were no
significant differences between groups in terms of VNRS, NDI, or BPI-SF scores.
However, TPI consisting of lidocaine mixed with hyaluronidase worked more
effectively than lidocaine alone on post-TPI day 1. Further, hyaluronidase showed
a tendency to reduce TPI-related soreness.
PMID- 26443390
TI - Application of ion mobility tandem mass spectrometry to compositional and
structural analysis of glycopeptides extracted from the urine of a patient
diagnosed with Schindler disease.
AB - RATIONALE: Schindler disease is caused by the deficient activity of alpha-N
acetylgalactosaminidase, which leads to an abnormal accumulation of O
glycopeptides in tissues and body fluids. In this work the Schindler condition is
for the first time approached by ion mobility (IMS) tandem mass spectrometry
(MS/MS), for determining urine glycopeptide fingerprints and discriminate
isomeric structures. METHODS: IMS-MS experiments were conducted on a Synapt G2s
mass spectrometer operating in negative ion mode. A glycopeptide mixture
extracted from the urine of a patient suffering from Schindler disease was
dissolved in methanol and infused into the mass spectrometer by electrospray
ionization using a syringe-pump system. MS/MS was performed by collision-induced
dissociation (CID) at low energies, after mobility separation in the transfer
cell. Data acquisition and processing were performed using MassLynx and Waters
Driftscope software. RESULTS: IMS-MS data indicated that the attachment of one or
two amino acids to the carbohydrate backbone has a minimal influence on the
molecule conformation, which limits the discrimination of the free
oligosaccharides from the glycosylated amino acids and dipeptides. The structural
analysis by CID MS/MS in combination with IMS-MS of species exhibiting the same
m/z but different configurations demonstrated for the first time the presence of
positional isomers for some of the Schindler disease biomarker candidates.
CONCLUSIONS: The IMS-MS and CID MS/MS platform was for the first time optimized
and applied to Schindler disease glycourinome. By this approach the separation
and characterization of Neu5Ac positional isomers was possible. IMS CID MS/MS
showed the ability to determine the type of the glycopeptide isomers from a
series of possible candidates.
PMID- 26443391
TI - The influence of different referencing methods on the accuracy of delta(13) C
value measurement of ethanol fuel by gas chromatography/combustion/isotope ratio
mass spectrometry.
AB - RATIONALE: Brazil is the largest producer of sugar cane bioethanol in the world.
Isotope ratio mass spectrometry (IRMS) is the technique of choice to certify the
origin/raw materials for ethanol production, but the lack of certified reference
materials (CRMs) for accurate measurements of delta(13) C values traceable to
Vienna Pee Dee Belemnite (VPDB), the international zero point for (13) C/(12) C
measurements, certified and compatible with gas chromatography (GC)/IRMS
instruments may compromise the accuracy of delta(13) C determinations. METHODS:
We evaluated the influence of methods for the calibration and normalization of
raw delta(13) C values of ethanol samples. Samples were analyzed by GC/C/IRMS
using two different GC columns. Different substances were used as isotopic
standards for the working gas calibration. The delta(13) C values obtained with
the three methods of normalization were statistically compared with those
obtained with elemental analyzer (EA)/IRMS, since the delta(13) C results
obtained using EA are traceable to VPDB via the NBS 22 reference material.
RESULTS: It was observed that both the isotopic reference material for CO2
calibration and the GC column have a major effect on the delta(13) C
measurements, leading to a bias of almost 2-3 0/00 in the delta(13) C values. All
three methods of normalization were equivalent in performance, enabling an
improvement in the GC/C/IRMS accuracy, compared with the EA/IRMS reference values
for the samples. CONCLUSIONS: All the methods of CO2 calibration, chromatography
and normalization presented in this work demonstrated several sources of
traceability and accuracy loss for the determination of delta(13) C values in
ethanol fuel samples by GC/C/IRMS. This work has also shown the importance of
using proper CRMs traceable to VPBD that should be compatible and certified using
GC/C/IRMS, ideally in a wide range of delta(13) C values. This is important not
only for bioethanol fuel samples, but also for many analytes commonly analyzed by
IRMS.
PMID- 26443392
TI - Fast screening of analytes for chemical reactions by reactive low-temperature
plasma ionization mass spectrometry.
AB - RATIONALE: Approaches for analyte screening have been used to aid in the fine
tuning of chemical reactions. Herein, we present a simple and straightforward
analyte screening method for chemical reactions via reactive low-temperature
plasma ionization mass spectrometry (reactive LTP-MS). METHODS: Solution-phase
reagents deposited on sample substrates were desorbed into the vapor phase by
action of the LTP and by thermal desorption. Treated with LTP, both reagents
reacted through a vapor phase ion/molecule reaction to generate the product.
Finally, protonated reagents and products were identified by LTP-MS. RESULTS:
Reaction products from imine formation reaction, Eschweiler-Clarke methylation
and the Eberlin reaction were detected via reactive LTP-MS. Products from the
imine formation reaction with reagents substituted with different functional
groups (26 out of 28 trials) were successfully screened in a time of 30 s each.
Besides, two short-lived reactive intermediates of Eschweiler-Clarke methylation
were also detected. CONCLUSIONS: LTP in this study serves both as an ambient
ionization source for analyte identification (including reagents, intermediates
and products) and as a means to produce reagent ions to assist gas-phase
ion/molecule reactions. The present reactive LTP-MS method enables fast screening
for several analytes from several chemical reactions, which possesses good
reagent compatibility and the potential to perform high-throughput analyte
screening. In addition, with the detection of various reactive intermediates
(intermediates I and II of Eschweiler-Clarke methylation), the present method
would also contribute to revealing and elucidating reaction mechanisms.
PMID- 26443393
TI - Soft Cold EI - approaching molecular ion only with electron ionization.
AB - RATIONALE: Cold EI is defined as electron ionization of cold molecules in
supersonic molecular beams (SMB). Gas chromatography/mass spectrometry (GC/MS)
with Cold EI provides informative mass spectra, which combine the usual library
searchable EI fragment ions with enhanced molecular ions for improved library
based identification probabilities. However, in some cases, such as in the
analysis of complex petrochemical matrices, a soft ionization method that
provides only molecular ions is desirable. METHODS: GC/MS with Cold EI was used
with a fly-through ion source at selected electron energies, including at low
electron energies, in an attempt to observe molecular ions alone. RESULTS: We
explored low electron energy Cold EI and found that once the sample compound is
cooled by the supersonic expansion it can be reheated via reflected scattered
helium atoms near the skimmer. Furthermore, once a labile molecular ion is formed
it can undergo undesirable collision-induced dissociation (CID) in the same way
as in tandem mass spectrometry (MS/MS), and the magnitude of such CID can be
significant for labile molecular ions such as those of hydrocarbons. In order to
reduce these adverse effects we reduced the helium pressure at the ion source and
MS vacuum chamber by increasing the nozzle-skimmer distance. Cold EI at low
electron energies was explored with a squalane isomer (C30 H62 ) and with n-C24
H50 . CONCLUSIONS: It was found that an increased nozzle-skimmer distance
resulted in a noticeable increase in the abundance ratio of molecular ions to low
mass fragment ions. Consequently, Cold EI at low electron energies and a large
nozzle-skimmer distance converts EI into Soft Cold EI while further approaching
the ideal of a molecular ion only ionization method.
PMID- 26443394
TI - Instrumental improvements and sample preparations that enable reproducible,
reliable acquisition of mass spectra from whole bacterial cells.
AB - RATIONALE: Rapid sub-species characterization of pathogens is required for timely
responses in outbreak situations. Pyrolysis mass spectrometry (PyMS) has the
potential to be used for this purpose. METHODS: However, in order to make PyMS
practical for traceback applications, certain improvements related to spectrum
reproducibility and data acquisition speed were required. The main objectives of
this study were to facilitate fast detection (<30 min to analyze 6 samples,
including preparation) and sub-species-level bacterial characterization based on
pattern recognition of mass spectral fingerprints acquired from whole cells
volatilized and ionized at atmospheric pressure. An AccuTOF DART mass
spectrometer was re-engineered to permit ionization of low-volatility bacteria by
means of Plasma Jet Ionization (PJI), in which an electric discharge, and, by
extension, a plasma beam, impinges on sample cells. RESULTS: Instrumental
improvements and spectral acquisition methodology are described. Performance of
the re-engineered system was assessed using a small challenge set comprised of
assorted bacterial isolates differing in identity by varying amounts. In general,
the spectral patterns obtained allowed differentiation of all samples tested,
including those of the same genus and species but different serotypes.
CONCLUSIONS: Fluctuations of +/-15% in bacterial cell concentrations did not
substantially compromise replicate spectra reproducibility.
PMID- 26443395
TI - Hyphenating size-exclusion chromatography with electrospray mass spectrometry;
using on-line liquid-liquid extraction to study the lipid composition of
lipoprotein particles.
AB - RATIONALE: Lipoproteins belong to the most commonly measured clinical biochemical
parameters. Lipidomics is an orthogonal approach and aims to profile the
individual lipid molecules that jointly form the lipoprotein particles. However,
in the first step of the extraction of lipid molecules from serum, an organic
solvent is used leading to dissociation of the lipoproteins. Thus far it has been
impossible to combine lipidomics and lipoprotein analysis in one analytical
system. METHODS: Human plasma was diluted in phosphate-buffered saline (PBS) and
injected onto a Superose 6 PC 3.2 column with PBS as a mobile phase to separate
lipoproteins. The eluent was led to a Syrris FLLEX module, which also received
CHCl3 /MeOH (3:1). The two phases were mixed and subsequently separated using a
Teflon membrane in an especially designed pressurized flow chamber. The organic
phase was led to a standard electrospray source of an Orbitrap mass spectrometer.
RESULTS: Size-exclusion chromatography (SEC) has been commonly applied to
separate lipoproteins and is considered a practical alternative to
ultracentrifugation. Through the on-line liquid-liquid extraction method it
becomes possible to obtained detailed mass spectra of lipids across different
lipoprotein fractions. The extracted ion chromatograms of specific lipid signals
showed their distribution against the size of lipoprotein particles. CONCLUSIONS:
The application of on-line liquid-liquid extraction allows for the continuous
electrospray-based mass spectral analysis of SEC eluent, providing the detailed
lipid composition of lipoprotein particles separated by size. This approach
provides new possibilities for the study of the biochemistry of lipoproteins.
PMID- 26443396
TI - Rapid determination of rivaroxaban in human urine and serum using colloidal
palladium surface-assisted laser desorption/ionization mass spectrometry.
AB - RATIONALE: Rivaroxaban is a new anticoagulant drug that has recently been
introduced for clinical applications. To ensure optimum efficacy while minimizing
the risk of toxicity and other adverse effects, a simple and sensitive analytical
procedure for monitoring the concentration of rivaroxaban in biological fluids is
required. METHODS: Rivaroxaban was extracted from aqueous solutions by dispersive
liquid-liquid microextraction (DLLME). Detection of rivaroxaban was achieved
through surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS)
using colloidal palladium as the SALDI matrix. RESULTS: The calibration curve for
rivaroxaban in aqueous solutions was linear over the concentration range from 5
to 500 nM. The limit of detection (LOD) for rivaroxaban at a signal-to-noise
ratio of 3 was 2 nM. With a sample-to-extract volume ratio of 200, the enrichment
factors were calculated to be 141. This method was successfully applied for the
determination of rivaroxaban in human urine and serum samples. The LODs for
rivaroxaban in urine and serum were calculated to be 6 nM and 60 nM,
respectively. CONCLUSIONS: The analysis speed, together with the ease of
operation and high sensitivity, allows SALDI-MS method to be particularly
suitable for the high-throughput screening of rivaroxaban levels in human urine
and serum samples.
PMID- 26443397
TI - Traceability of different apple varieties by multivariate analysis of isotope
ratio mass spectrometry data.
AB - RATIONALE: The awareness of customers of the origin of foods has become an
important issue. The growing demand for foods that are healthy, safe and of high
quality has increased the need for traceability and clear labelling. Thus, this
study investigates the capability of C and N stable isotope ratios to determine
the geographical origin of several apple varieties grown in northern Italy.
METHODS: Four apple varieties (Cripps Pink, Gala, Golden Delicious, Granny Smith)
have been sampled in orchards located in the Districts of Bolzano, Ferrara,
Verona and Udine (northern Italy). Carbon (delta(13) C) and nitrogen (delta(15)
N) isotope values of the whole apple fruits and three sub-fractions (peel, pulp
and seed) have been determined simultaneously by isotope ratio mass spectrometry.
RESULTS: The delta(13) C and delta(15) N values of apples and apple sub
fractions, such as peel, seed and pulp, were significantly affected by the
geographical origin and the fruit variety. The four varieties could be
distinguished to a certain extent only within each district. A 99% correct
identification of the samples according to their origin was, however, achieved by
cross validation with the 'leave-one-out' method. CONCLUSIONS: This study proves
the potential of stable isotopes to discriminate the geographical origin of
apples grown in orchards located only a few hundreds of kilometres apart. Stable
isotopes were also able to discriminate different apple varieties, although only
within small geographical areas.
PMID- 26443398
TI - Comparison of methods to determine triple oxygen isotope composition of N2O.
AB - RATIONALE: The oxygen isotope anomaly, Delta(17) O, of N2 O and nitrate is useful
to elucidate nitrogen oxide dynamics. A comparison of different methods for
Delta(17) O measurement was performed. METHODS: For Delta(17) O measurements, N2
O was converted into O2 and N2 using microwave-induced plasma in a quartz or
corundum tube reactor, respectively, or conversion was carried out in a gold wire
oven. In each case, isotope ratios were measured by isotope ratio mass
spectrometry. RESULTS: All the tested methods showed acceptable precision
(coefficient of variation <2.4 % at 160 nmol N2 O) with high sample size but the
sample size dependence was lowest when using microwave-induced plasma in a
corundum tube reactor. CONCLUSIONS: The use of microwave-induced plasma in a
corundum tube yields best results for Delta(17) O measurement on N2 O gas
samples.
PMID- 26443399
TI - Simultaneous analysis of (17) O/(16) O, (18) O/(16) O and (2) H/(1) H of gypsum
hydration water by cavity ring-down laser spectroscopy.
AB - RATIONALE: The recent development of cavity ring-down laser spectroscopy (CRDS)
instruments capable of measuring (17) O-excess in water has created new
opportunities for studying the hydrologic cycle. Here we apply this new method to
studying the triple oxygen ((17) O/(16) O, (18) O/(16) O) and hydrogen ((2) H/(1)
H) isotope ratios of gypsum hydration water (GHW), which can provide information
about the conditions under which the mineral formed and subsequent post
depositional interaction with other fluids. METHODS: We developed a semi
automated procedure for extracting GHW by slowly heating the sample to 400
degrees C in vacuo and cryogenically trapping the evolved water. The isotopic
composition (delta(17) O, delta(18) O and delta(2) H values) of the GHW is
subsequently measured by CRDS. The extraction apparatus allows the dehydration of
five samples and one standard simultaneously, thereby increasing the long-term
precision and sample throughput compared with previous methods. The apparatus is
also useful for distilling brines prior to isotopic analysis. A direct comparison
is made between results of (17) O-excess in GHW obtained by CRDS and fluorination
followed by isotope ratio mass spectrometry (IRMS) of O2 . RESULTS: The long-term
analytical precision of our method of extraction and isotopic analysis of GHW by
CRDS is +/-0.070/00 for delta(17) O values, +/-0.130/00 for delta(18) O values
and +/-0.490/00 for delta(2) H values (all +/-1SD), and +/-1.10/00 and +/-8 per
meg for the deuterium-excess and (17) O-excess, respectively. Accurate
measurement of the (17) O-excess values of GHW, of both synthetic and natural
samples, requires the use of a micro-combustion module (MCM). This accessory
removes contaminants (VOCs, H2 S, etc.) from the water vapour stream that
interfere with the wavelengths used for spectroscopic measurement of water
isotopologues. CRDS/MCM and IRMS methods yield similar isotopic results for the
analysis of both synthetic and natural gypsum samples within analytical error of
the two methods. CONCLUSIONS: We demonstrate that precise and simultaneous
isotopic measurements of delta(17) O, delta(18) O and delta(2) H values, and the
derived deuterium-excess and (17) O-excess, can be obtained from GHW and brines
using a new extraction apparatus and subsequent measurement by CRDS. This method
provides new opportunities for the application of water isotope tracers in
hydrologic and paleoclimatologic research.
PMID- 26443400
TI - Identification of bacteria by fatty acid profiling with direct analysis in real
time mass spectrometry.
AB - RATIONALE: Bacterial fatty acid profiling is a well-established technique for
bacterial identification. Current methods involving esterification and gas
chromatography/mass spectrometry (GC/MS) or matrix-assisted laser
desorption/ionization (MALDI) analysis are effective, but there are potential
benefits to be gained by investigating ambient ionization methods that can
provide rapid analysis without derivatization or additional sample handling.
METHODS: Lipid extracts from colonies of five Gram-positive and five Gram
negative pathogenic bacteria were analyzed by Direct Analysis in Real Time (DART)
ionization coupled with a time-of-flight mass spectrometer. Fatty acid profiles
were obtained from the negative-ion DART mass spectra without additional
derivatization or sample preparation. RESULTS: Fatty acid profiles obtained from
the deprotonated molecules [M - H](-) were found to be highly species-specific
and reproducible. Leave-one-out cross validation (LOOCV) for principal component
analysis (PCA) showed 100% correct classification accuracy. CONCLUSIONS: The
results of this preliminary feasibility study show good precision and accuracy,
and the fatty acid patterns are clearly distinctive for each of the ten species
examined. The speed and ease of analysis and the high classification accuracy for
this initial study indicate that DART is an effective method for bacterial fatty
acid profiling.
PMID- 26443401
TI - Chemical lipid extraction or mathematical isotope correction models: should
mathematical models be widely applied to marine species?
AB - RATIONALE: Chemical lipid extractions, as means of standardizing sample
preparations, have been identified as important for comparability of studies.
Unfortunately, these methods are expensive, because of the costly chemicals and
the need to analyse two sets of samples, one for delta(13) C values (treated) and
another for delta(15) N values (untreated). To avoid this, studies have suggested
mathematical solutions to the problem. Our study intends to (i) determine the
applicability of the five most common mathematical correction models and (ii)
which of the widely applied chemical extraction methods is the most suitable for
a variety of marine organisms. METHODS: Muscle, heart and liver samples were
collected from eight different species. The tissues were treated with Bligh and
Dyer, Folch and Soxhlet extraction methods and analysed in a Europa 20-20 mass
spectrometer. Predicted lipid-extracted delta(13) C values were calculated from
untreated tissue values using the five most common mathematical models. RESULTS:
The results indicated that the mathematical methods could not be accurately
applied to any of the eight species used in this study, highlighting current
issues with accepted isotope methodologies. The Folch chemical extraction removed
the highest amount of lipid, suggesting it is the most suitable delipidation
method. CONCLUSIONS: Analysing two samples, one treated one not, remains the best
method to obtain accurate delta(13) C isotope values of muscle tissue. By using
this approach every study will obtain two datasets, eventually providing a
suitable collective dataset for determining how isotopic signatures are affected
by delipidation and potentially producing better mathematical correction models
in future.
PMID- 26443402
TI - Site-specific (13) S/(12) S isotope abundance ratios in dicarboxylic oxyacids as
characteristics of their origin.
AB - RATIONALE: Recommendations of relevant international organizations controlling
the quality of grape wines and beverages specify that only tartaric acids of
grape origin can be introduced to achieve the required parameters. The
development of methods for determining the origin of tartaric acid in grape wine
is of great technological significance. METHODS: Organic dicarboxylic oxyacids
were extracted from wines as barium salts. Carbon dioxide, which included all the
carbon atoms of the acids, was used to determine the carbon isotope ratios by
Isotope Ratio Mass Spectrometry. The alkyl part of the oxyacids was burned at 560
degrees C in the presence of air; BaCO3 containing the carboxyl carbon was left.
This carbonate was used to measure the carbon isotope ratios in the carboxyl part
of the acid. The carbon isotope ratios of the alkyl part of tartaric acid were
found by isotope mass balance. RESULTS: The carbon isotope composition of
carboxyl groups (delta(13) S values) in tartaric acid of grape (biogenic origin)
had a higher (13) S content than the carbon in the alkyl part of the molecule.
Tartaric acid produced by chemical synthesis (abiogenic origin) was noted to have
a different (13) S/(12) S distribution: the carboxyl group of tartaric acid
produced by chemical synthesis contained a smaller than or equal amount of (13) S
to the alkyl part. CONCLUSIONS: This is the first determination of the site
specific distribution of the (13) S/(12) S isotopes in tartaric acids as evidence
of their biogenic and abiogenic origins. The presented method for determining the
origin of tartaric acid can be used for efficient control of the quality of grape
wines and beverages.
PMID- 26443403
TI - Study of the non-covalent interactions of ginsenosides and lysozyme using
electrospray ionization mass spectrometry.
AB - RATIONALE: Ginsenosides are an important class of natural products extracted from
ginseng that possess various important biological activities. Studies of
interactions of ginsenosides with proteins are essential for comprehensive
understanding of the biological activities of ginsenosides. In this study, the
interactions of ginsenosides with lysozyme were investigated by electrospray
ionization mass spectrometry (ESI-MS). METHODS: Both protopanaxadiol-type and
protopanaxatriol-type ginsenosides were chosen to explore the interactions of
ginsenosides towards lysozyme near the physiological conditions by direct ESI-MS,
respectively. Comparative experiments were conducted to confirm the interactions
were specific. In addition, the dissociation constants of ginsenoside-lysozyme
complexes were determined by a ESI-MS titration strategy. RESULTS: The results
showed ginsenosides bound to lysozyme at the stoichiometries of 1:1 and 2:1. The
association constants of ginsenosides to lysozyme were in the order of
Re>Rd>Rf>Rg2 >Rg3 . According to their structures, the binding affinities
associated with the type of aglycone and the type and the number of sugar
moieties linked on the aglycone. CONCLUSIONS: It has been demonstrated that ESI
MS is a powerful tool to probe the non-covalent interactions between lysozyme and
ginsenosides. These results provide insights into the interaction of ginsenosides
with lysozyme at the molecular level. The developed strategy could be applied to
determine the interactions of proteins with other natural products.
PMID- 26443404
TI - Oxygen isotope studies of phosphite oxidation: purification and analysis of
reactants and products by high-temperature conversion elemental analyzer/isotope
ratio mass spectrometry.
AB - RATIONALE: Increased attention has been recently focused on the origin and
reactions of reduced-P oxyanions such as phosphite [PO3 (III)] in terrestrial and
biological systems. We present new methods for studying O-isotopic reactions
between PO3 (III) and other oxygen sources during oxidation of PO3 (III) to PO4
(V). METHODS: Na2 (HPO3 ).5H2 O, used as a PO3 (III) source, contains structural
water due to its hygroscopic nature; thus, we developed a method for determining
the delta(18) O value of PO3 (III) after the removal of structural water. Next,
we tested two techniques for purifying PO4 (V) from aqueous PO3 (III)/PO4 (V)
mixtures: (1) precipitation of PO4 (V) as ammonium phosphomolybdate (APM); and
(2) precipitation of PO4 (V) as magnesium ammonium phosphate (MAP). The O-isotope
compositions, (18) O:(16) O (delta(18) O values), of Na2 (HPO3 ) and Ag3 PO4 were
analyzed by TC/EA/IRMS. RESULTS: Structural water was removed from Na2 (HPO3
).5H2 O after drying at 100 degrees C under vacuum and the delta(18) O value of
PO3 (III) was obtained. The delta(18) O values of PO4 (V), which was extracted
from (18) O-labeled PO3 (III)/PO4 (V) mixtures by APM and MAP precipitations,
were not altered by the precipitation process. This result confirms that PO3
(III) is not converted into PO4 (V) by oxidation or hydrolysis under either
strong acidic/oxidizing (APM) or alkaline (MAP) conditions for up to a 24-h
period. CONCLUSIONS: We conclude that both APM and MAP precipitation are reliable
and effective methods for the separation and purification of PO4 (V) from aqueous
PO3 (III)/PO4 (V) mixtures. The methods described here will permit the study of
the isotopic evolution of various pathways of geochemical as well as biological
PO3 (III) oxidation.
PMID- 26443405
TI - Comparative metabolism of four limonoids in human liver microsomes using ultra
high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap
mass spectrometry.
AB - RATIONALE: Limonoids, characterized by a triterpenoid skeleton with a furan ring,
are unique secondary metabolites widely distributed in the families of Rutaceae,
particularly in Citrus species and Meliaceae. Studies on health benefits have
demonstrated that limonoids have a range of biological activities. Dietary intake
of citrus limonoids may provide a protective effect against the onset of various
cancers and other xenobiotic related diseases. However, few studies about the
metabolic profiles of limonoids have been carried out. METHODS: The objectives of
this study were to investigate the metabolic profiles of four limonoids (limonin,
obacunone, nominin and gedunin) in human liver microsomes (HLMs) using ultra-high
performance liquid chromatography coupled with high-resolution mass spectrometry
(UHPLC/HRMS) and to identify the cytochrome P450 (CYP) enzymes involved in the
formation of their metabolites by recombinant human CYP enzymes. RESULTS: Based
on the accurate HR-MS/MS spectra and the proposed MS/MS fragmentation pathways,
four metabolites of limonin (M1-1, M1-2, M1-3 and M1-4), eight metabolites
ofobacunone (M2-1, M2-2, M2-3, M2-4, M2-5, M2-6, M2-7 and M2-8), six metabolites
of nominin (M3-1, M3-2, M3-3, M3-4, M3-5 and M3-6) and three metabolites of
gedunin (M4-1, M4-2 and M4-3) in HLMs were tentatively identified and the
involved CYPs were investigated. CONCLUSIONS: The results demonstrated that
reduction at C-7 and C-16, hydroxylation and reaction of glycine with reduction
limonoids were the major metabolic pathways of limonoids in HLMs. Among them,
glycination with reduction was the unique metabolic process of limonoids observed
for the first time. CYP2D6 and CYP3A4 played an important role in the
isomerization and glycination of limonoids in HLMs, whereas other CYP isoforms
were considerably less active. The results might help to understand the metabolic
process of limonoids in vitro such as the unidentified metabolites of limonin
glucoside observed in the medium of microbes and the biotransformation of limonin
in juices. Moreover, it would be beneficial for us to further study the
pharmacokinetic behavior of limonoids in vivo systematically.
PMID- 26443406
TI - Using matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry to detect monoclonal immunoglobulin light chains in serum and urine.
AB - RATIONALE: Use of matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry (MALDI-TOFMS) to monitor serum and urine samples for endogenous
monoclonal immunoglobulins. MALDI-TOFMS is faster, fully automatable, and
provides superior specificity compared to protein gel electrophoresis (PEL).
METHODS: Samples were enriched for immunoglobulins in 5 min using Melon GelTM
followed by reduction with dithiothreitol for 15 min to separate immunoglobulin
light chains and heavy chains. Samples were then desalted using C4 ZipTips, mixed
with sinapinic acid matrix, and analyzed on a Bruker Biflex III MALDI-TOF mass
spectrometer. RESULTS: Monoclonal immunoglobulin light chains were identified in
serum and urine samples from patients with a known monoclonal gammopathy using
MALDI-TOFMS with minimal sample preparation. CONCLUSIONS: MALDI-TOFMS can
identify a monoclonal immunoglobulin in serum and urine samples. The molecular
mass of the monoclonal immunoglobulin light chain is obtained providing
unprecedented specificity compared to PEL. In addition, the methodology can be
automated, making it a practical alternative to PEL.
PMID- 26443407
TI - Skin secretion peptides: the molecular facet of the deimatic behavior of the four
eyed frog, Physalaemus nattereri (Anura, Leptodactylidae).
AB - RATIONALE: Amphibians can produce a large amount of bioactive peptides over the
skin. In order to map the precise tissue localization of these compounds and
evaluate their functions, mass spectrometry imaging (MSI) and gene expression
studies were used to investigate a possible correlation between molecules
involved in the antimicrobial defense mechanisms and anti-predatory behavior by
Physalaemus nattereri. METHODS: Total skin secretion of P. nattereri was analyzed
by classical Protein Chemistry and proteomic techniques. Intact inguinal
macroglands were dissected from the rest of the skin and both tissues were
analyzed by MSI and real-time polymerase chain reaction (RT-PCR) experiments.
Peptides were primarily identified by de novo sequencing, automatic Edman
degradation and cDNA data. RESULTS: Fifteen bradykinin (BK)-related peptides and
two antimicrobial peptides were sequenced and mapped by MSI on the inguinal
macrogland and the rest of P. nattereri skin. RT-PCR results revealed that BK
related peptide levels of expression were about 30,000 times higher on the
inguinal macroglands than on the any other region of the skin, whilst
antimicrobial peptide ions appear to be evenly distributed in both investigated
regions. CONCLUSIONS: The presence of antimicrobial peptides in all investigated
tissue regions is in accordance with the defensive role against microorganisms
thoroughly demonstrated in the literature, whereas BK-related molecules are
largely found on the inguinal macroglands suggesting an intriguing link between
their noxious activities against potential predators of P. nattereri and the
frog's deimatic behavior.
PMID- 26443408
TI - Fish tissue lipid-C:N relationships for correcting delta(13) C values and
estimating lipid content in aquatic food-web studies.
AB - RATIONALE: Normalizing delta(13) C values of animal tissue for lipid content is
necessary to accurately interpret food-web relationships from stable isotope
analysis. To reduce the effort and expense associated with chemical extraction of
lipids, various studies have tested arithmetic mass balance to mathematically
normalize delta(13) C values for lipid content; however, the approach assumes
that lipid content is related to the tissue C:N ratio. METHODS: We evaluated two
commonly used models for estimating tissue lipid content based on C:N ratio (a
mass balance model and a stoichiometric model) by comparing model predictions to
measure the lipid content of white muscle tissue. We then determined the effect
of lipid model choice on delta(13) C values normalized using arithmetic mass
balance. To do so, we used a collection of fish from Lake Superior spanning a
wide range in lipid content (5% to 73% lipid). RESULTS: We found that the lipid
content was positively related to the bulk muscle tissue C:N ratio. The two
different lipid models produced similar estimates of lipid content based on
tissue C:N, within 6% for tissue C:N values <7. Normalizing delta(13) C values
using an arithmetic mass-balance equation based on either model yielded similar
results, with a small bias (<10/00) compared with results based on chemical
extraction. CONCLUSIONS: Among-species consistency in the relationship between
fish muscle tissue C:N ratio and lipid content supports the application of
arithmetic mass balance to normalize delta(13) C values for lipid content. The
uncertainty associated with both lipid extraction quality and choice of model
parameters constrains the achievable precision of normalized delta(13) C values
to about +/-1.00/00.
PMID- 26443409
TI - A new isotopic reference material for stable hydrogen and oxygen isotope-ratio
measurements of water - USGS50 Lake Kyoga Water.
AB - RATIONALE: As a result of the need for isotopic reference waters having high
delta(2) HVSMOW-SLAP and delta(18) OVSMOW-SLAP values for daily use, especially
for tropical and equatorial-zone freshwaters, a new secondary isotopic reference
material for international distribution was prepared from water collected from
Lake Kyoga, Uganda. METHODS: This isotopic reference lakewater was filtered
through a membrane with 0.2-um pore size, homogenized, loaded into glass ampoules
that were sealed with a torch and autoclaved to eliminate biological activity,
and measured by dual-inlet isotope-ratio mass spectrometry. This reference
material is available in a case of 144 glass ampoules each containing 5 mL of
water. RESULTS: The delta(2) H and delta(18) O values of this reference material
are +32.8 +/- 0.4 and +4.95 +/- 0.02 mUr (milliurey = 0.001 = 1 0/00),
respectively, relative to VSMOW, on scales normalized such that the delta(2) H
and delta(18) O values of SLAP reference water are, respectively, -428 and -55.5
mUr. Each uncertainty is an estimated expanded uncertainty (U = 2uc ) about the
reference value that provides an interval that has about a 95 % probability of
encompassing the true value. CONCLUSIONS: This isotopic reference material,
designated as USGS50, is intended as one of two reference waters for daily
normalization of stable hydrogen and oxygen isotopic analysis of water with an
isotope-ratio mass spectrometer or a laser absorption spectrometer, of use
especially for isotope-hydrology laboratories analyzing freshwater samples from
equatorial and tropical regions.
PMID- 26443411
TI - Formation of amino acids from NH3 /NO2, CO2 and H2O: implications for the
prebiotic origin of biomolecules.
AB - RATIONALE: The search for the conditions which must have prevailed in the long
distant past during the conversion of inanimate matter into animate matter is a
fascinating area of research and it continues to draw the attention of the
scientific community. The initiation of life on this planet must have been
preceded by the development of biomolecules, amongst which amino acids have
unique importance. Formation of amino acids under a certain set of conditions is
shown in the present experiments. METHODS: Solutions of ammonium carboxylates or
the mixture of two such salts were prepared in 3:6.9:0.1 (v/v/v)
acetonitrile/water/formic acid at a concentration of 50 MUM. The studies were
performed using a quadrupole time-of-flight (QqTOF) mass spectrometer. The
formation of different amino acids was detected with high-resolution mass
spectrometry. RESULTS: Here, we show the formation of amino acids when a solution
of ammonium salts was injected into an electrospray ionization (ESI)-QqTOF-MS
instrument. The ammonium salts were the source of NH3 and CO2 and H2 O was
available in the medium. It seems that the combination of NH3 , CO2 , and H2 O
leads to the formation of amino acids. CONCLUSIONS: Further to the literature
reports of formation of amino acids under the reduced atmosphere represented by
gases such as NH3 , CH4 , H2 and H2 O, here we demonstrate the formation of amino
acids by the combination of NH3 /NO2 , CO2 and water vapours in the ESI source of
the mass spectrometer.
PMID- 26443410
TI - Software-aided structural elucidation in drug discovery.
AB - RATIONALE: Structural information on metabolites obtained in relevant biological
systems can have considerable impact on the design of new drug candidates.
However, with demanding turnaround times, the amount of available structural
information may become rate limiting. METHODS: The workflow for metabolite
identification used in our laboratory was compared to a workflow using a software
tool built for computer-assisted metabolite identification. The present study
covered the in vitro metabolism of a diverse set of 65 in-house compounds. The
compounds were profiled across three liver-based systems, 17 compounds were
tested in human liver microsomes (HLM), 12 in rat hepatocytes (RHEP), and 36 in
human hepatocytes (HHEP). RESULTS: For 92% of the metabolites reported, the exact
match or Markush representations were in agreement between the two workflows. The
major specific biotransformations in hepatocytes which formed the metabolites
were aromatic or aliphatic hydroxylations (33%), N-dealkylations (15%) and
glucuronidations (12%). CONCLUSIONS: The software was shown to perform well for
structural elucidation of metabolites from both phase I and phase II metabolism
where the focus was on quickly understanding the rate-limiting metabolic step(s).
PMID- 26443412
TI - Mechanistic study on lowering the sensitivity of positive atmospheric pressure
photoionization mass spectrometric analyses: size-dependent reactivity of solvent
clusters.
AB - RATIONALE: Understanding the mechanism of atmospheric pressure photoionization
(APPI) is important for studies employing APPI liquid chromatography/mass
spectrometry (LC/MS). In this study, the APPI mechanism for polyaromatic
hydrocarbon (PAH) compounds dissolved in toluene and methanol or water mixture
was investigated by use of MS analysis and quantum mechanical simulation. In
particular, four different mechanisms that could contribute to the signal
reduction were considered based on a combination of MS data and quantum
mechanical calculations. METHODS: The APPI mechanism is clarified by combining MS
data and density functional theory (DFT) calculations. To obtain MS data, a
positive-mode (+) APPI Q Exactive Orbitrap mass spectrometer was used to analyze
each solution. DFT calculations were performed using the general atomic and
molecular electronic structure system (GAMESS). RESULTS: The experimental results
indicated that methanol significantly reduced the signal in (+) APPI, but no
significative signal reduction was observed when water was used as a co-solvent
with toluene. The signal reduction is more significant especially for molecular
ions than for protonated ions. Therefore, important information about the
mechanism of methanol-induced signal reduction in (+) APPI-MS can be gained due
its negative impact on APPI efficiency. CONCLUSIONS: The size-dependent
reactivity of methanol clusters ((CH3 OH)n , n = 1-8) is an important factor in
determining the sensitivity of (+) APPI-MS analyses. Clusters can compete with
toluene radical ions for electrons. The reactivity increases as the sizes of the
methanol clusters increase and this effect can be caused by the size-dependent
ionization energy of the solvent clusters. The resulting increase in cluster
reactivity explains the flow rate and temperature-dependent signal reduction
observed in the analytes. Based on the results presented here, minimizing the
sizes of methanol clusters can improve the sensitivity of LC/(+)-APPI-MS.
PMID- 26443413
TI - Effects of different water storage procedures on the dissolved Fe concentration
and isotopic composition of chemically contrasted waters from the Amazon River
Basin.
AB - RATIONALE: Although recent studies have investigated the Fe isotopic composition
of dissolved, colloidal and particulate phases from continental and oceanic
natural waters, few efforts have been made to evaluate whether water sample
storage and the separation of different pore-size fractions through filtration
can cause any change to the Fe isotopic compositions. The present study
investigates the possible biases introduced by different water storage conditions
on the dissolved Fe concentration and isotopic composition of chemically
different waters. METHODS: Water samples were collected from an organic-rich
river and from mineral particulate-rich rivers. Filtered and unfiltered water
samples were stored either at room temperature or frozen at -18 degrees C in
order to assess possible biases due to (i) different water storage temperature,
and (ii) storage of bulk (unfiltered) vs filtered water. Iron isotope
measurements were performed by Multicollector Inductively Coupled Plasma Mass
Spectrometry with a Thermo Electron Neptune instrument, after Fe purification
using anion-exchange resins. RESULTS: Our data reveal that bulk water storage at
room temperature without filtration produces minor changes in the dissolved Fe
isotopic composition of mineral particulate-rich waters, but significant isotopic
composition changes in organic-rich waters. In both cases, however, the impact of
the different procedures on the Fe concentrations was strong. On the other hand,
the bulk water stored frozen without filtration produced more limited changes in
the dissolved Fe concentrations, and also on isotopic compositions, relative to
the samples filtered in the field. The largest effect was again observed for the
organic-rich waters. CONCLUSIONS: These findings suggest that a time lag between
water collection and filtration may cause isotopic exchanges between the
dissolved and particulate Fe fractions. When it is not possible to filter the
samples in the field immediately after collection, the less detrimental approach
is to freeze the bulk water sample until filtration, to reduce isotopic
artifacts.
PMID- 26443414
TI - Long-term storability of water samples in vials used with laser absorption
isotope analyzers.
PMID- 26443415
TI - A Novel In Vitro Technique for Assessing Dental Implant Osseointegration.
AB - By definition, osseointegration means close contact between bone and implant.
Bone response is related to implant surface properties. Various surfaces have
been studied and applied to improve the biological properties of the implant and
thereby favor the mechanism of osseointegration. This strategy aims to promote
osseointegration by means of a faster and stronger bone formation, improving
stability during the healing process, and thus allowing for earlier loading of
the implant. Dental implant osseointegration has so far been studied in various
animal models. The development of a method based on tissue engineering for
assessing the osseointegration process in vitro could prove a valid biomimetic
alternative to sacrificing animals. In this study, flat cylindrical dental
implants with moderately rough surfaces and machined implants were set in bovine
bone blocks. Then, adipose-derived stem cells (ADSCs) were three dimensionally
cultured onto these blocks in osteo-endothelial medium for up to 30 days to mimic
the osseointegration process in vitro. Scanning electron microscopy (SEM) and
gene expression were used to examine stem cell commitment. Mechanical pull-out
tests were also performed. SEM analysis identified cells with an osteoblast
morphology adhering to the surface of the implants after their removal. Gene
expression analysis showed that ADSCs seeded onto the bone blocks were able to
express osteoblast and endothelial markers. The implants with the moderately
rough surface generated higher pull-out strengths when compared with the machined
implants. Nevertheless, the pull-out test values were higher for implants placed
in bone blocks with ADSCs than for those set in scaffolds without stem cells. Our
results demonstrate the validity of the method adopted and its potential for use
in the in vitro assessment of the biological behavior of dental implant surfaces.
PMID- 26443416
TI - RNA approaches the B-form in stacked single strand dinucleotide contexts.
AB - Duplex RNA adopts an A-form structure, while duplex DNA interconverts between the
A- and B-forms depending on the environment. The C2'-endo sugar pucker seen in B
form DNA can occur infrequently in ribose sugars as well, but RNA is not
understood to assume B-form conformations. Through analysis of over 45,000
stacked single strand dinucleotide (SSD) crystal structure conformations, this
study demonstrates that RNA is capable of adopting a wide conformational range
between the canonical A- and B-forms at the localized SSD level, including many B
form-like conformations. It does so through C2'-endo ribose conformations in one
or both nucleotides, and B-form-like neighboring base stacking patterns. As
chemical reactions on nucleic acids involve localized changes in chemical bonds,
the understanding of how enzymes distinguish between DNA and RNA nucleotides is
altered by the energetic accessibility of these rare B-form-like RNA SSD
conformations. The existence of these conformations also has direct implications
in parametrization of molecular mechanics energy functions used extensively to
model nucleic acid behavior., 2016. (c) 2015 Wiley Periodicals, Inc. Biopolymers
105: 65-82, 2016.
PMID- 26443417
TI - Childhood wheezing, asthma, allergy, atopy, and lung function: different
socioeconomic patterns for different phenotypes.
AB - Identifying preventable exposures that lead to asthma and associated allergies
has proved challenging, partly because of the difficulty in differentiating
phenotypes that define homogeneous disease groups. Understanding the
socioeconomic patterns of disease phenotypes can help distinguish which exposures
are preventable. In the present study, we identified disease phenotypes that are
susceptible to socioeconomic variation, and we determined which life-course
exposures were associated with these inequalities in a contemporary birth cohort.
Participants included children from the Avon Longitudinal Study of Parents and
Children, a population-based birth cohort in England, who were born in 1991 and
1992 and attended the clinic at 7-8 years of age (n = 6,378). Disease phenotypes
included asthma, atopy, wheezing, altered lung function, and bronchial reactivity
phenotypes. Combining atopy with a diagnosis of asthma from a doctor captured the
greatest socioeconomic variation, including opposing patterns between phenotype
groups: Children with a low socioeconomic position (SEP) had more asthma alone
(adjusted multinomial odds ratio = 1.50, 95% confidence interval: 1.21, 1.87) but
less atopy alone (adjusted multinomial odds ratio = 0.80, 95% confidence
interval: 0.66, 0.98) than did children with high SEP. Adjustment for maternal
exposure to tobacco smoke during pregnancy and childhood exposure to tobacco
smoke reduced the odds of asthma alone in children with a low SEP. Current
inequalities among children who have asthma but not atopy can be prevented by
eliminating exposure to tobacco smoke. Other disease phenotypes were not socially
patterned or had SEP patterns that were not related to smoke exposure.
PMID- 26443418
TI - Childhood body weight in relation to morbidity from cardiovascular disease and
cancer in older adulthood: 67-year follow-up of participants in the 1947 Scottish
Mental Survey.
AB - Although it has been well documented that elevated body weight in middle- and
older-aged populations is associated with multiple morbidities, the influence of
childhood body weight on health endpoints other than coronary heart disease is
not well understood. Accordingly, using a subsample of 4,620 participants (2,288
women) from the Scottish Mental Survey of 1947, we examined the association
between body mass index measured at 11 years of age and future risk of 9
independent health endpoints as ascertained from national hospital admissions and
cancer registers until 2014 (up to age 77 years). Although there was some
evidence of a relationship between elevated childhood body mass index and higher
rates of peripheral vascular disease (per each 1-standard deviation increase in
body mass index, hazard ratio = 1.21, 95% confidence interval: 1.07, 1.37) and
smoking-related cancers (per each 1-standard deviation increase in body mass
index, hazard ratio = 1.09, 95% confidence interval: 1.01, 1.17), there was no
apparent association with coronary heart disease, stroke (including ischemic
stroke), heart failure, or carcinomas of the colorectum, stomach, lung, prostate,
or breast. In conclusion, a relationship between childhood body weight and later
morbidity was largely lacking in the present study.
PMID- 26443419
TI - From Smallpox to Big Data: The Next 100 Years of Epidemiologic Methods.
AB - For more than a century, epidemiology has seen major shifts in both focus and
methodology. Taking into consideration the explosion of "big data," the advent of
more sophisticated data collection and analytical tools, and the increased
interest in evidence-based solutions, we present a framework that summarizes 3
fundamental domains of epidemiologic methods that are relevant for the
understanding of both historical contributions and future directions in public
health. First, the manner in which populations and their follow-up are defined is
expanding, with greater interest in online populations whose definition does not
fit the usual classification by person, place, and time. Second, traditional data
collection methods, such as population-based surveillance and individual
interviews, have been supplemented with advances in measurement. From biomarkers
to mobile health, innovations in the measurement of exposures and diseases enable
refined accuracy of data collection. Lastly, the comparison of populations is at
the heart of epidemiologic methodology. Risk factor epidemiology, prediction
methods, and causal inference strategies are areas in which the field is
continuing to make significant contributions to public health. The framework
presented herein articulates the multifaceted ways in which epidemiologic methods
make such contributions and can continue to do so as we embark upon the next 100
years.
PMID- 26443420
TI - Optimal use of available claims to identify a Medicare population free of
coronary heart disease.
AB - We examined claims-based approaches for identifying a study population free of
coronary heart disease (CHD) using data from 8,937 US blacks and whites enrolled
during 2003-2007 in a prospective cohort study linked to Medicare claims. Our
goal was to minimize the percentage of persons at study entry with self-reported
CHD (previous myocardial infarction or coronary revascularization). We assembled
6 cohorts without CHD claims by requiring 6 months, 1 year, or 2 years of
continuous Medicare fee-for-service insurance coverage prior to study entry and
using either a fixed-window or all-available look-back period. We examined adding
CHD-related claims to our "base algorithm," which included claims for myocardial
infarction and coronary revascularization. Using a 6-month fixed-window look-back
period, 17.8% of participants without claims in the base algorithm reported
having CHD. This was reduced to 3.6% using an all-available look-back period and
adding other CHD claims to the base algorithm. Among cohorts using all-available
look-back periods, increasing the length of continuous coverage from 6 months to
1 or 2 years reduced the sample size available without lowering the percentage of
persons with self-reported CHD. This analysis demonstrates approaches for
developing a CHD-free cohort using Medicare claims.
PMID- 26443422
TI - Terahertz meets sculptural and architectural art: Evaluation and conservation of
stone objects with T-ray technology.
AB - Conservation of cultural heritage is an area where novel scientific techniques
are having enormous impact. Given the value and uniqueness of art pieces, non
invasive diagnostic methods are highly appreciated by conservators. Terahertz
radiation has shown enormous potential as non-contact probe that can be used for
the three-dimensional reconstruction of internal structure of stone-made objects.
In this article we report the evaluation of the internal damage state of two art
pieces, a medallion from the Castle of Celle and a window sill from the St. Peter
of Trier Cathedral. We also used terahertz radiation to follow and assess the
restoration process of the window sill. We found that terahertz spectroscopy is
an excellent non-destructive evaluation method for stone artwork that shows
enormous potential as a tool for conservation.
PMID- 26443421
TI - Risk of thyroid follicular adenoma among children and adolescents in Belarus
exposed to iodine-131 after the Chornobyl accident.
AB - Several studies reported an increased risk of thyroid cancer in children and
adolescents exposed to radioactive iodines, chiefly iodine-131 ((131)I), after
the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of
benign thyroid tumors following such radiation exposure is much less well known.
We have previously reported a novel finding of significantly increased risk of
thyroid follicular adenoma in a screening study of children and adolescents
exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed
baseline screening data from a cohort of 11,613 individuals aged <=18 years at
the time of the accident in Belarus (mean age at screening = 21 years). All
participants had individual (131)I doses estimated from thyroid radioactivity
measurements and were screened according to a standardized protocol. We found a
significant linear dose response for 38 pathologically confirmed follicular
adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval:
0.41, 13.1) was similar in males and females but decreased significantly with
increasing age at exposure (P < 0.01), with the highest radiation risks estimated
for those exposed at <2 years of age. Follicular adenoma radiation risks were not
significantly modified by most indicators of past and current iodine deficiency.
The present study confirms the (131)I-associated increases in risk of follicular
adenoma in the Ukrainian population and adds new evidence on the risk increasing
with decreasing age at exposure.
PMID- 26443423
TI - Insights into Mechanistic Models for Evaporation of Organic Liquids in the
Environment Obtained by Position-Specific Carbon Isotope Analysis.
AB - Position-specific isotope effects (PSIEs) have been measured by isotope ratio
monitoring (13)C nuclear magnetic resonance spectrometry during the evaporation
of 10 liquids of different polarities under 4 evaporation modes (passive
evaporation, air-vented evaporation, low pressure evaporation, distillation). The
observed effects are used to assess the validity of the Craig-Gordon isotope
model for organic liquids. For seven liquids the overall isotope effect (IE)
includes a vapor-liquid contribution that is strongly position-specific in polar
compounds but less so in apolar compounds and a diffusive IE that is not position
specific, except in the alcohols, ethanol and propan-1-ol. The diffusive IE is
diminished under forced evaporation. The position-specific isotope pattern
created by liquid-vapor IEs is manifest in five liquids, which have an air-side
limitation for volatilization. For the alcohols, undefined processes in the
liquid phase create additional PSIEs. Three other liquids with limitations on the
liquid side have a lower, highly position-specific, bulk diffusive IE. It is
concluded that evaporation of organic pollutants creates unique position-specific
isotope patterns that may be used to assess the progress of remediation or
natural attenuation of pollution and that the Craig-Gordon isotope model is valid
for the volatilization of nonpolar organic liquids with air-side limitation of
the volatilization rate.
PMID- 26443424
TI - Contingent non-invasive prenatal testing: an opportunity to improve non-genetic
aspects of fetal aneuploidy screening.
AB - BACKGROUND: Several countries today struggle with suboptimal performances in many
aspects of the fetal aneuploidy screening process and consider introducing non
invasive prenatal screening (NIPT) as a solution. In this study, costs and
benefits of different scenarios for contingent NIPT screening in Belgium are
evaluated with respect to partial redistribution of the national screening budget
into quality improving measures for those screening activities that will be
maintained when full NIPT screening is implemented. METHODS: Data from the
Belgian National Institute for Health and Disability Insurance and the Study
Centre for Perinatal Epidemiology were used in modeled calculations of medical
and economic impact of NIPT after prior conventional screening (1) at thresholds
1:300 and 1:600, and (2) at current and improved screening sensitivity. RESULTS:
Contingent NIPT screening under current screening conditions would maintain
today's 7.9(0)/000 live birth prevalence of Down syndrome (LBPD) at an 11%
reduction of overall short-term costs. Lowering the screening threshold to 1:600
or increasing sensitivity by 10% would reduce LBPD to 7(0)/000 at a maximum 3%
increase of overall short-term costs. CONCLUSION: Today, in Belgium and in many
other countries, full NIPT screening is considered too expensive for immediate
introduction into the national fetal aneuploidy screening program. Contingent
NIPT screening is both clinically and economically beneficial. A temporary
contingent NIPT protocol allows for reinvesting economic savings into
optimization of those screening aspects, which are to be maintained in parallel
to full NIPT screening.
PMID- 26443425
TI - Is left ventricular diastolic function impaired in patients with ankylosing
spondylitis?
PMID- 26443426
TI - Household physical activity and cancer risk: a systematic review and dose
response meta-analysis of epidemiological studies.
AB - Controversial results of the association between household physical activity and
cancer risk were reported among previous epidemiological studies. We conducted a
meta-analysis to investigate the relationship of household physical activity and
cancer risk quantitatively, especially in dose-response manner. PubMed, Embase,
Web of science and the Cochrane Library were searched for cohort or case-control
studies that examined the association between household physical activity and
cancer risks. Random-effect models were conducted to estimate the summary
relative risks (RRs), nonlinear or linear dose-response meta-analyses were
performed to estimate the trend from the correlated log RR estimates across
levels of household physical activity quantitatively. Totally, 30 studies
including 41 comparisons met the inclusion criteria. Total cancer risks were
reduced 16% among the people with highest household physical activity compared to
those with lowest household physical activity (RR = 0.84, 95% CI = 0.76-0.93).
The dose-response analyses indicated an inverse linear association between
household physical activity and cancer risk. The relative risk was 0.98 (95% CI =
0.97-1.00) for per additional 10 MET-hours/week and it was 0.99 (95% CI = 0.98
0.99) for per 1 hour/week increase. These findings provide quantitative data
supporting household physical activity is associated with decreased cancer risk
in dose-response effect.
PMID- 26443427
TI - Direct electron transfer from photosystem II to hematite in a hybrid
photoelectrochemical cell.
AB - A hybrid photoanode integrating the cyanobacterial photosystem II (PSII) with a
hematite film for water oxidation is constructed. Direct electron transfer from
PSII to the excited Ti/Fe2O3 electrode occurs under light irradiation, resulting
in a significant improvement of the photocurrent.
PMID- 26443428
TI - Reply from Authors re: Julia Verne, Luke Hounsome, Roger Kockelbergh, Jem
Rashbass. Improving Outcomes from Prostate Cancer: Unlocking the Treasure Trove
of Information in Cancer Registries. Eur Urol 2016;69:1013-4.
PMID- 26443429
TI - Urology Tag Ontology Project: Standardizing Social Media Communication
Descriptors.
AB - Standardizing social media hashtag descriptors is likely to facilitate
communication and promote collaboration in both health care provider and patient
communities.
PMID- 26443430
TI - Reply from Authors re: Ronald C. Chen. Decisions Regarding Whether to Use
Androgen Deprivation Therapy with Radiotherapy in Prostate Cancer: Is
Cardiovascular Mortality the Most Relevant Outcome? Eur Urol 2016;69:211-2:
Outcomes for Favorable and Unfavorable Intermediate Risk Prostate Cancer Patients
Receiving Radiation Therapy With or Without Short-term Androgen Deprivation
Therapy.
PMID- 26443431
TI - Detailed Quantification of High-grade Cancer Allows Precise Prediction of
Prostate Cancer Prognosis.
PMID- 26443432
TI - Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor
Signaling Reflect Anatomic Tumor Location.
AB - Prostate cancer (PCa) subtypes based on ETS gene expression have been described.
Recent studies suggest there are racial differences in tumor location, with PCa
located anteriorly more often among African-American (AA) compared to Caucasian
American (CA) men. In this retrospective analysis of a multi-institutional cohort
treated by radical prostatectomy (179 CA, 121 AA), we evaluated associations
among molecular subtype, race, anatomic tumor location, and androgen receptor
(AR) signaling. Subtype (m-ERG(+), m-ETS(+), m-SPINK1(+), or triple-negative) was
determined using distribution-based outlier analysis. AR signaling was
investigated using gene expression profiling of canonical AR targets. m-ERG(+)
was more common in CA than AA men (47% vs 22%, p<0.001). AA men were more likely
to be m-SPINK1(+) (13% vs 7%; p=0.069) and triple-negative (50% vs 37%; p=0.043).
Racial differences in molecular subtypes did not persist when tumors were
analyzed by location, suggesting a biologically important relationship between
tumor location and subtype. Accordingly, anterior tumor location was associated
with higher Decipher scores and lower global AR signaling. PATIENT SUMMARY: This
study demonstrates associations among patient race, prostate cancer molecular
subtypes, and tumor location. Location-specific differences in androgen
regulation may further underlie these relationships.
PMID- 26443433
TI - Molecular dynamics simulations for designing biomimetic pores based on internally
functionalized self-assembling alpha,gamma-peptide nanotubes.
AB - A molecular dynamics study on internally functionalized peptide nanotubes
composed of alpha- and gamma-amino acids self-assembled in lipid bilayers is
presented. One of the main advantages of peptide nanotubes composed of gamma
amino acids is that the properties of their inner cavities can be tuned by
introducing different functions on beta-carbon of the gamma-amino acid. In the
work described here we studied the effect of the presence of different numbers of
hydroxyl groups in different positions in the lumen of these channels when they
are inserted into a lipid bilayer and assessed how they affect the structural and
dynamic behavior of the modified peptide nanotubes as well as the transmembrane
transport of different ions. The results provided atomic information about the
effect of polar groups on the dynamic, structural and transport properties of
this type of peptidic channel upon insertion into lipid bilayers, projecting a
promising future for their use as biomimetic channels when properly inner
derivatized. Furthermore, the chemical versatility of the hydroxyl groups in the
lumen of the peptide nanotubes would enable appealing applications for these
channels, such as a controlled method for the activation/inactivation of the
transmembrane transport along the nanopore.
PMID- 26443434
TI - Identification of cross-reactivity between buckwheat and coconut.
PMID- 26443435
TI - Effect modification by race-ethnicity of environmental tobacco smoke exposure on
airway inflammation in US children.
AB - BACKGROUND: Asthma mortality and morbidity are higher in black than in white
children. Fractional exhaled nitric oxide (FeNO) is a noninvasive biomarker of
eosinophilic airway inflammation. Identification of differences in the effect of
environmental tobacco smoke (ETS) on airway inflammation by race and ethnicity
from a large sample is needed. OBJECTIVE: To estimate a racial difference in
association with ETS and FeNO. METHODS: Data from the 2007 to 2012 National
Health and Nutrition Examination Survey were analyzed to compare associations of
ETS and FeNO levels in US black and other children. No ETS exposure was defined
as a serum cotinine level lower than 0.05 ng/mL and ETS exposure was defined as a
serum cotinine level of at least 0.05 ng/mL. FeNO was measured using a device
that relies on an electrochemical sensor. Analyses took the complex survey design
into account. RESULTS: The analytic sample was formed by 5,473 participants (6-11
years old, n = 2,385; 12-19 years old, n = 3,088) with complete data on
demographics, serum cotinine levels, and 2 reproducible FeNO measurements. In
weighted linear regression analyses at 6 to 11 years, the interaction term for
ETS and black race was not significant (P = .15). At 12 to 19 years, the
interaction term was significant (P = .03) in an analysis of all racial groups.
In race-specific models, the coefficient for ETS exposure in blacks was -0.033
and that in others was -0.175, ie, ETS exposure was associated with a greater
decrease in FeNO in non-blacks than in blacks. CONCLUSION: There was no evidence
at 6 to 11 years of age for an effect modification by race of the association
between ETS and FeNO. At 12 to 19 years, the data suggested an effect
modification.
PMID- 26443436
TI - Spontaneous regression of laryngeal squamous cell carcinoma.
AB - BACKGROUND: Spontaneous regression of solid malignancy is extremely rare. It is
virtually unheard of in the last half century in the published literature. The
overwhelming majority of medical professionals do not know that this phenomenon
exists. CASE REPORT: This paper reports such a case involving a patient with
proven laryngeal squamous cell carcinoma in New Zealand. Whilst waiting for
definitive treatment, he was afflicted with prolonged septicaemia secondary to
peritonitis from percutaneous endoscopic gastrostomy tube insertion. Following a
total laryngectomy, histology of the specimen did not contain any evidence of
neoplasia. CONCLUSION: Based predominantly on work established by Dr William
Coley, we believe that a period of prolonged pyrexia preceding definitive surgery
contributed to this apparent 'miracle'. The time may be ripe to further debate on
whether the medical profession should consider pyrexia therapy as a last resort
treatment for patients deemed incurable by conventional methods.
PMID- 26443437
TI - Individual Vaccination as Nash Equilibrium in a SIR Model with Application to the
2009-2010 Influenza A (H1N1) Epidemic in France.
AB - The vaccination against ongoing epidemics is seldom compulsory but remains one of
the most classical means to fight epidemic propagation. However, recent debates
concerning the innocuity of vaccines and their risk with respect to the risk of
the epidemic itself lead to severe vaccination campaign failures, and new mass
behaviors appeared driven by individual self-interest. Prompted by this context,
we analyze, in a Susceptible-Infected-Recovered model, whether egocentric
individuals can reach an equilibrium with the rest of the society. Using
techniques from the "Mean Field Games" theory, we extend previous results and
show that an equilibrium exists and characterizes completely the individual best
vaccination strategy (with or without discounting). We also compare with a
strategy based only on overall societal optimization and exhibit a situation with
nonnegative price of anarchy. Finally, we apply the theory to the 2009-2010
Influenza A (H1N1) vaccination campaign in France and hint that a group of
individuals stopped vaccinating at levels that indicated a pessimistic perception
of the risk of the vaccine.
PMID- 26443438
TI - Negotiability of Second Mesiobuccal Canals in Maxillary Molars Using a
Reciprocating System.
AB - The aim of this prospective case series report was to assess the frequency in
which the Reciproc R25 instrument (VDW, Munich, Germany) is able to scout and
reach the full working length (WL) in second mesiobuccal (MB2) canals from
maxillary molars. Conventional hand file negotiation was used as the reference
technique for comparison. Maxillary molars (270 first molars and 71 second
molars) were included in this study. After local anesthesia, the tooth was
isolated with a rubber dam, and traditional straight-line access was made. After
locating both first mesiobuccal and MB2 canals, patients were randomly assigned
to one of the experimental groups (conventional hand filing preparation or R25
Reciproc preparation). All cases in which the hand files (G1) and R25 instrument
(G2) were able to reach the fully electronically determined WL were classified as
"reaching full WL" (RFWL). All cases in which the hand files (G1) and R25
instrument (G2) were unable to negotiate the full-length canal were classified as
"not reaching full WL" (NRFWL). The number of root canals classified as RFWL and
NRFWL from both groups were recorded and tabulated on an Excel data sheet
(Microsoft, Redmond, WA). The frequency distributions (%) of root canals
classified as RFWL and NRFWL were compared with overall-treated canals and for
each treatment approach (hand file and R25 instrument) using a Pearson chi-square
test. In group 1, the hand file approach reached the full WL in 57.48% of cases,
whereas in group 2 the R25 instrument reached the full WL in 85.63% of cases.
Three file separations occurred in each group while negotiating the MB2 canal.
According to this study, the R25 instrument was 32% more effective when compared
with hand files in scouting and negotiating MB2 canals in maxillary first and
second molars. There was no difference with regard to file separation when
comparing both preparation techniques.
PMID- 26443439
TI - Fermi states and anisotropy of Brillouin zone scattering in the decagonal Al-Ni
Co quasicrystal.
AB - Quasicrystals (QCs) are intermetallic alloys that have excellent long-range order
but lack translational symmetry in at least one dimension. The valence band
electronic structure near the Fermi energy EF in such materials is of special
interest since it has a direct relation to their unusual physical properties.
However, the Fermi surface (FS) topology as well as the mechanism of QC structure
stabilization are still under debate. Here we report the first observation of the
three-dimensional FS and valence band dispersions near EF in decagonal
Al70Ni20Co10 (d-AlNiCo) QCs using soft X-ray angle-resolved photoemission
spectroscopy. We show that the FS, formed by dispersive Al sp-states, has a
multicomponent character due to a large contribution from high-order bands.
Moreover, we discover that the magnitude of the gap at the FS related to the
interaction with Brillouin zone boundary (Hume-Rothery gap) critically differs
for the periodic and quasiperiodic directions.
PMID- 26443440
TI - Density-gradient centrifugation enables the purification of cultured corneal
endothelial cells for cell therapy by eliminating senescent cells.
AB - The corneal endothelium is essential for maintaining corneal transparency;
therefore, corneal endothelial dysfunction causes serious vision loss. Tissue
engineering-based therapy is potentially a less invasive and more effective
therapeutic modality. We recently started a first-in-man clinical trial of cell
based therapy for treating corneal endothelial dysfunction in Japan. However, the
senescence of corneal endothelial cells (CECs) during the serial passage culture
needed to obtain massive quantities of cells for clinical use is a serious
technical obstacle preventing the push of this regenerative therapy to clinical
settings. Here, we show evidence from an animal model confirming that senescent
cells are less effective in cell therapy. In addition, we propose that density
gradient centrifugation can eliminate the senescent cells and purify high potency
CECs for clinical use. This simple technique might be applicable for other types
of cells in the settings of regenerative medicine.
PMID- 26443441
TI - Dynamic Expression Patterns of Progenitor and Neuron Layer Markers in the
Developing Human Dentate Gyrus and Fimbria.
AB - The molecular mechanisms that orchestrate the development of the human dentate
gyrus are not known. In this study, we characterized the formation of human
dentate and fimbrial progenitors and postmitotic neurons from 9 gestational weeks
(GW9) to GW25. PAX6+ progenitor cells remained proliferative until GW16 in the
dentate ventricular zone. By GW11, the secondary dentate matrix had developed in
the intermediate zone, surrounding the dentate anlage and streaming toward the
subpial layer. This secondary matrix contained proliferating PAX6+ and/or TBR2+
progenitors. In parallel, SOX2+ and PAX6+ fimbrial cells were detected
approaching the dentate anlage, representing a possible source of extra-dentate
progenitors. By GW16, when the granule cell layer could be delineated, a hilar
matrix containing PAX6+ and some TBR2+ progenitors had become identifiable. By
GW25, when the 2 limbs of the granule cell layer had formed, the secondary
dentate matrix was reduced to a pool of progenitors at the fimbrio-dentate
junction. Although human dentate development recapitulates key steps previously
described in rodents, differences seemed to emerge in neuron layer markers
expression. Further studies are necessary to better elucidate their role in
dentate formation and connectivity.
PMID- 26443442
TI - Dopamine D1 Receptor-Mediated Transmission Maintains Information Flow Through the
Cortico-Striato-Entopeduncular Direct Pathway to Release Movements.
AB - In the basal ganglia (BG), dopamine plays a pivotal role in motor control, and
dopamine deficiency results in severe motor dysfunctions as seen in Parkinson's
disease. According to the well-accepted model of the BG, dopamine activates
striatal direct pathway neurons that directly project to the output nuclei of the
BG through D1 receptors (D1Rs), whereas dopamine inhibits striatal indirect
pathway neurons that project to the external pallidum (GPe) through D2 receptors.
To clarify the exact role of dopaminergic transmission via D1Rs in vivo, we
developed novel D1R knockdown mice in which D1Rs can be conditionally and
reversibly regulated. Suppression of D1R expression by doxycycline treatment
decreased spontaneous motor activity and impaired motor ability in the mice.
Neuronal activity in the entopeduncular nucleus (EPN), one of the output nuclei
of the rodent BG, was recorded in awake conditions to examine the mechanism of
motor deficits. Cortically evoked inhibition in the EPN mediated by the cortico
striato-EPN direct pathway was mostly lost during suppression of D1R expression,
whereas spontaneous firing rates and patterns remained unchanged. On the other
hand, GPe activity changed little. These results suggest that D1R-mediated
dopaminergic transmission maintains the information flow through the direct
pathway to appropriately release motor actions.
PMID- 26443443
TI - Substantial differences in initiation of oral anticoagulant therapy and clinical
outcome among non-valvular atrial fibrillation patients treated in inpatient and
outpatient settings.
AB - AIMS: Patients with atrial fibrillation (AF) are encountered and treated in
different healthcare settings, which may affect the quality of care. We
investigated the use of oral anticoagulant (OAC) therapy and the risk of thrombo
embolism (TE) and bleeding, according to the healthcare setting. METHODS AND
RESULTS: Using national Danish registers, we categorized non-valvular AF patients
(2002-11) according to the setting of their first-time AF contact:
hospitalization (inpatients), ambulatory (outpatients), or emergency department
(ED). Event rates and hazard ratios (HRs), calculated using Cox regression
analysis, were estimated for outcomes of TE and bleeding. We included 116 051 non
valvular AF patients [mean age 71.9 years (standard deviation 14.1), 51.3%
males], of whom 55.2% were inpatients, 41.9% outpatients, and 2.9% ED patients.
OAC therapy 180 days after AF diagnosis among patients with a CHADS2 >= 2 was
42.1, 63.0, and 32.4%, respectively. Initiation of OAC therapy was only modestly
influenced by CHADS2 and HAS-BLED scores, regardless of the healthcare setting.
The rate of TE was 4.30 [95% confidence interval (CI) 4.21-4.40] per 100 person
years for inpatients, 2.28 (95% CI 2.22-2.36) for outpatients, and 2.30 (95% CI
2.05-2.59) for ED patients. The adjusted HR of TE, with inpatients as reference,
was 0.74 (95% CI 0.71-0.77) for outpatients and 0.89 (95% CI 0.79-1.01) for ED
patients. CONCLUSION: In a nationwide cohort of non-valvular AF patients,
outpatients were much more likely to receive OAC therapy and had a significantly
lower risk of stroke/TE compared with inpatients and ED patients. However, across
all settings investigated, OAC therapy was far from optimal.
PMID- 26443444
TI - The risk of atrial fibrillation during right ventricular pacing.
AB - AIMS: Right ventricular pacing adversely affects left atrial (LA) structure and
function that may trigger atrial fibrillation (AF). This study compares the
occurrence of persistent/permanent AF during long-term Hisian area (HA), right
ventricular septal (RVS), and right ventricular apex (RVA) pacing in patients
with complete/advanced atrioventricular block (AVB). METHODS AND RESULTS: We
collected retrospective data from 477 consecutive patients who underwent
pacemaker implantation for complete/advanced AVB. Ventricular pacing leads were
located in the HA, RVS, and RVA in 148, 140, and 189 patients, respectively. The
occurrence of persistent/permanent AF was observed in 114 (23.9%) patients
(follow-up 58.5 +/- 26.5 months). Hisian area groups presented a lower rate of AF
occurrence (16.9%) compared with RVS and RVA groups (25.7 and 28.0%,
respectively), P = 0.049. Cox's proportional hazard model was used to estimate
HR. The risk of persistent/permanent AF was significantly lower in the patients
paced from HA compared with those paced from RVA, HR = 0.28 (95% CI 0.16-0.48, P
= 0.0001). The RVS and RVA pacing groups showed a similar AF risk: HR 1.04 (95%
CI 0.66-1.64, P = 0.856). Other independent predictors of persistent/permanent AF
occurrence included previous (before device implantation) paroxysmal AF (HR =
4.08; 95% CI 3.15-7.31, P = 0.0001), LA diameter, and age, whereas baseline
bundle-branch block was associated with a lower risk of AF occurrence (HR = 0.56;
95% CI 0.35-0.81, P = 0.003). CONCLUSIONS: HA pacing compared with RVA or RVS
pacing seems to be associated with a lower risk of persistent/permanent AF
occurrence. The risk of persistent/permanent AF was similar in the RVA vs. RVS
groups.
PMID- 26443445
TI - Effect of caffeine on ventricular arrhythmia: a systematic review and meta
analysis of experimental and clinical studies.
AB - AIMS: The relationship between caffeine consumption and the occurrence of
arrhythmias remains controversial. Despite this lack of scientific evidence,
counselling to reduce caffeine consumption is still widely advised in clinical
practice. We conducted a systematical review and meta-analysis of interventional
studies of the caffeine effects on ventricular arrhythmias. METHODS AND RESULTS:
The search was performed on Pubmed, Embase, and Cochrane database, and terms
related to coffee, caffeine, and cardiac arrhythmias were used. Methodological
quality was assessed based on The Cochrane Collaboration recommendations and the
ARRIVE guidelines. There were 2016 citations retrieved on the initial research.
After full-text assessment, seven human and two animal studies were included in
the meta-analysis. In animal studies, the main outcome reported was the
ventricular fibrillation threshold. We observed a significant mean difference of
2.15 mA (95% CI -3.43 to -0.87; I(2) 0.0%, P for heterogeneity = 0.37). The main
outcome evaluated in human studies was the rate of ventricular premature beats
(VPBs). The overall relative risk for occurrence of VPBs in 24 h attributed to
caffeine exposure was 1.00 (95% CI 0.94-1.06; I(2) 13.5%, P for heterogeneity =
0.32). Sensitivity analysis for caffeine dose, different designs, and subject
profile was performed and no major differences were observed. CONCLUSION: Our
meta-analysis demonstrates that data from human interventional studies do not
show a significant effect of caffeine consumption on the occurrence of VBPs. The
effects observed in animal studies are most probably the result of very high
caffeine doses that are not regularly consumed in a daily basis by humans.
PMID- 26443446
TI - Tilt testing results are influenced by tilt protocol.
AB - AIMS: It is unknown how the return to supine position influences duration of loss
of consciousness (LOC) and cardioinhibition during tilt test. METHODS AND
RESULTS: Retrospective analysis of two datasets containing records of patients
who underwent tilt testing for unexplained syncope in two centres was performed.
Patients, totalling 1232, were included in the study: 262 in a Swedish centre and
970 patients in a Polish centre. In Sweden, tilt table with tilt-down time (TDT)
of 18 s was used (Group II). In Poland, two different tilt tables were used, one
of them with TDT of 10 s (Group I, n = 325), and the other with TDT of 47 s
(Group III, n = 645). Cardioinhibitory reflex occurred most frequently in Group
III, whereas number of pauses >3 s, frequency of very long asystole >=30 s, and
the total duration of pauses >3 s demonstrated a trend to increase from Group I
to III. Duration of LOC in Groups II and III was significantly longer compared
with Group I (32.0 and 33.7 s vs. 16.4 s). In the multivariate-adjusted
regression model, cardioinhibitory reflex was predicted by tilt-table model (odds
ratio per model with increasing TDT: 1.40; 95% confidence interval, 1.19-1.64; P
< 0.0001), whereas LOC duration was longer with increasing TDT (P < 0.0001) and
age (P < 0.0001). CONCLUSION: Longer TDT during induced vasovagal syncope
increases the prevalence of cardioinhibitory reflex and prolongs the duration of
LOC. Tilt-down time does not affect asystolic pause duration but delay may lead
to occurrence of multiple pauses, higher frequency of very long asystole, and
longer total asystole duration.
PMID- 26443447
TI - Active fixation of a thin transvenous left-ventricular lead by a side helix
facilitates targeted and stable placement in cardiac resynchronization therapy.
AB - AIMS: Suboptimal placement, phrenic nerve stimulation, and dislodgements of left
ventricular (LV) leads are main challenges in cardiac resynchronization therapy.
We investigated the handling, performance, safety, and stability for a novel 4Fr
LV lead with a small side helix located proximal to the ring electrode for active
fixation of the LV lead. METHODS AND RESULTS: The novel LV lead was successfully
implanted in 103 of 106 patients. Patients with dislodged LV leads and with
demanding coronary vein anatomies were included. The lead body was rotated
clockwise to engage the active fixation side helix in the vein wall. The
stimulating electrode was located in basal LV segment and middle LV segment in 54
and 46% of the patients, respectively. The lead was targeted to a vein concordant
to the LV segment with latest mechanical activation. Concordant LV lead placement
was achieved in 73% of the patients and in adjacent segment in 24%. The average
pacing capture threshold (PCT) at implantation was 1.04 +/- 0.6 V (n = 103) and
at an average follow-up at 7 months, the PCT remained low and no dislodgements
have been observed. During follow-up, four leads have been explanted without
complications. CONCLUSION: Active fixation of this 4Fr LV lead by using a side
helix, offers flexibility to place the lead precisely in targeted vein segments
over a wide range of vein anatomies. The average LV pacing threshold was low at
implantation and follow-ups. The lead seems to be extractable and no late
dislodgements have been observed.
PMID- 26443448
TI - [Not Available].
PMID- 26443450
TI - Constriction of the ductus arteriosus, severe right ventricular hypertension, and
a right ventricular aneurysm in a fetus after maternal use of a topical treatment
for striae gravidarum.
AB - Fetal constriction of the ductus arteriosus is a complication of maternal non
steroidal anti-inflammatory drug use and polyphenol-rich food intake. It is
unclear as to whether polyphenol-containing topical treatments have similar
effects. We present a case of fetal constriction of the ductus arteriosus, severe
right ventricular hypertension, and a right ventricular aneurysm associated with
maternal use of a topical treatment for striae gravidarum.
PMID- 26443449
TI - Large-scale association analysis in Asians identifies new susceptibility loci for
prostate cancer.
AB - Genome-wide association studies (GWAS) have identified ~100 genetic loci
associated with prostate cancer risk. Less than a dozen of these loci were
initially identified from GWAS in two Asian populations, likely because of
smaller sample sizes of these individual GWAS in Asians. Here, we conduct a large
scale meta-analysis of two GWAS from the Japanese population (1,583 cases and
3,386 controls) and the Chinese population (1,417 cases and 1,008 controls),
followed by replication in three independent sample sets. We identify two
independent susceptibility loci for prostate cancer at 11p15.4 (rs12791447,
P=3.59 * 10(-8); PPFIBP2) and 14q23.2 (rs58262369, P=6.05 * 10(-10); ESR2). The
mRNA levels of PPFIBP2 and ESR2 are differentially expressed in prostate tumours
and paired normal tissues. Our study adds two new loci to the limited number of
prostate cancer risk-associated variants in Asians and provides important insight
into potential biological mechanisms of prostate cancer.
PMID- 26443451
TI - The imaging conundrum of hepatic lymphoma revisited.
AB - The imaging manifestations of hepatic lymphoma, both in its primary and secondary
form, are extremely variable and overlap with a number of other more common
hepatic diseases. However, in the appropriate clinical context, combining the
imaging and laboratory features can aid in making the correct diagnosis. Since
the management and prognosis of lymphomas are significantly different from other
malignancies, early diagnosis and prompt commencement of therapy is of paramount
importance. The various morphological appearances of hepatic lymphoma on imaging
have been described here along with their possible differentials. TEACHING
POINTS: * Primary hepatic lymphoma is extremely rare. * Secondary liver
involvement occurs in 50 % of patients with non-Hodgkin lymphoma. * The imaging
manifestations of hepatic lymphoma are largely non-specific. * Some imaging
features may be helpful in the appropriate clinical setting. * Management and
prognosis of lymphoma is significantly different from other malignancies.
PMID- 26443452
TI - Cancer therapy related complications in the liver, pancreas, and biliary system:
an imaging perspective.
AB - Awareness of cancer therapy-induced toxicities is important for all clinicians
treating patients with cancer. Cancer therapy has evolved to include classic
cytotoxic agents in addition to newer options such as targeted agents and
catheter-directed chemoembolisation. Several adverse affects can result from the
wide array of treatments including effects on the liver, pancreas, and biliary
system that can be visualised on imaging. These complications include sinusoidal
obstruction syndrome, fatty liver, pseudocirrhosis, acute hepatitis,
pancreatitis, pancreatic atrophy, cholecystitis, biliary sclerosis, and biliary
stasis. Many of these toxicities are manageable and reversible with supportive
therapies and/or cessation of cancer therapy. The objective of this review is to
discuss the imaging findings associated with cancer therapy-induced toxicity of
the liver, biliary system, and pancreas. TEACHING POINTS: * Cancer therapy can
have adverse effects on the hepatobiliary system and pancreas. * Cancer therapy
induced toxicities can be visualised on imaging. * Knowledge of imaging changes
associated with cancer therapy complications can improve treatment.
PMID- 26443453
TI - Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with
Lactobacillus crispatus-Dominant Microbiota.
AB - Cervicovaginal mucus (CVM) can provide a barrier that precludes HIV and other
sexually transmitted virions from reaching target cells in the vaginal
epithelium, thereby preventing or reducing infections. However, the barrier
properties of CVM differ from woman to woman, and the causes of these variations
are not yet well understood. Using high-resolution particle tracking of
fluorescent HIV-1 pseudoviruses, we found that neither pH nor Nugent scores nor
total lactic acid levels correlated significantly with virus trapping in
unmodified CVM from diverse donors. Surprisingly, HIV-1 was generally trapped in
CVM with relatively high concentrations of d-lactic acid and a Lactobacillus
crispatus-dominant microbiota. In contrast, a substantial fraction of HIV-1
virions diffused rapidly through CVM with low concentrations of d-lactic acid
that had a Lactobacillus iners-dominant microbiota or significant amounts of
Gardnerella vaginalis, a bacterium associated with bacterial vaginosis. Our
results demonstrate that the vaginal microbiota, including specific species of
Lactobacillus, can alter the diffusional barrier properties of CVM against HIV
and likely other sexually transmitted viruses and that these microbiota
associated changes may account in part for the elevated risks of HIV acquisition
linked to bacterial vaginosis or intermediate vaginal microbiota. IMPORTANCE:
Variations in the vaginal microbiota, especially shifts away from Lactobacillus
dominant microbiota, are associated with differential risks of acquiring HIV or
other sexually transmitted infections. However, emerging evidence suggests that
Lactobacillus iners frequently colonizes women with recurring bacterial
vaginosis, raising the possibility that L. iners may not be as protective as
other Lactobacillus species. Our study was designed to improve understanding of
how the cervicovaginal mucus barrier against HIV may vary between women along
with the vaginal microbiota and led to the finding that the vaginal microbiota,
including specific species of Lactobacillus, can directly alter the diffusional
barrier properties of cervicovaginal mucus. This work advances our understanding
of the complex barrier properties of mucus and highlights the differential
protective ability of different species of Lactobacillus, with Lactobacillus
crispatus and possibly other species playing a key role in protection against HIV
and other sexually transmitted infections. These findings could lead to the
development of novel strategies to protect women against HIV.
PMID- 26443454
TI - Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA
by RIG-I.
AB - Stimulation of the antiviral response depends on the sensing of viral pathogen
associated molecular patterns (PAMPs) by specialized cellular proteins. During
infection with RNA viruses, 5'-di- or -triphosphates accompanying specific single
or double-stranded RNA motifs trigger signaling of intracellular RIG-I-like
receptors (RLRs) and initiate the antiviral response. Although these molecular
signatures are present during the replication of many viruses, it is unknown
whether they are sufficient for strong activation of RLRs during infection.
Immunostimulatory defective viral genomes (iDVGs) from Sendai virus (SeV) are
among the most potent natural viral triggers of antiviral immunity. Here we
describe an RNA motif (DVG(70-114)) that is essential for the potent
immunostimulatory activity of 5'-triphosphate-containing SeV iDVGs. DVG(70-114)
enhances viral sensing by the host cell independently of the long stretches of
complementary RNA flanking the iDVGs, and it retains its stimulatory potential
when transferred to otherwise inert viral RNA. In vitro analysis showed that
DVG(70-114) augments the binding of RIG-I to viral RNA and promotes enhanced RIG
I polymerization, thereby facilitating the onset of the antiviral response.
Together, our results define a new natural viral PAMP enhancer motif that
promotes viral recognition by RLRs and confers potent immunostimulatory activity
to viral RNA. IMPORTANCE: A discrete group of molecular motifs, including 5'
triphosphates associated with double-stranded RNA, have been identified as
essential for the triggering of antiviral immunity. Most RNA viruses expose these
motifs during their replication; however, successful viruses normally evade
immune recognition and replicate to high levels before detection, indicating that
unknown factors drive antiviral immunity. DVGs from SeV are among the most potent
natural viral stimuli of the antiviral response known to date. These studies
define a new natural viral motif present in DVGs that maximizes viral recognition
by the intracellular sensor RIG-I, allowing fast and strong antiviral responses
even in the presence of viral-encoded immune antagonists. This motif can be
harnessed to increase the immunostimulatory potential of otherwise inert viral
RNAs and represents a novel immunostimulatory enhancer that could be used in the
development of vaccine adjuvants and antivirals.
PMID- 26443455
TI - Sphingosine Kinase Regulates Microtubule Dynamics and Organelle Positioning
Necessary for Proper G1/S Cell Cycle Transition in Trypanosoma brucei.
AB - Sphingolipids are important constituents of cell membranes and also serve as
mediators of cell signaling and cell recognition. Sphingolipid metabolites such
as sphingosine-1-phosphate and ceramide regulate signaling cascades involved in
cell proliferation and differentiation, autophagy, inflammation, and apoptosis.
Little is known about how sphingolipids and their metabolites function in single
celled eukaryotes. In the present study, we investigated the role of sphingosine
kinase (SPHK) in the biology of the protozoan parasite Trypanosoma brucei, the
agent of African sleeping sickness. T. brucei SPHK (TbSPHK) is constitutively but
differentially expressed during the life cycle of T. brucei. Depletion of TbSPHK
in procyclic-form T. brucei causes impaired growth and attenuation in the G1/S
phase of the cell cycle. TbSPHK-depleted cells also develop organelle positioning
defects and an accumulation of tyrosinated alpha-tubulin at the elongated
posterior end of the cell, known as the "nozzle" phenotype, caused by other
molecular perturbations in this organism. Our studies indicate that TbSPHK is
involved in G1-to-S cell cycle progression, organelle positioning, and
maintenance of cell morphology. Cytotoxicity assays using TbSPHK inhibitors
revealed a favorable therapeutic index between T. brucei and human cells,
suggesting TbSPHK to be a novel drug target. IMPORTANCE: Trypanosoma brucei is a
single-celled parasite that is transmitted between humans and other animals by
the tsetse fly. T. brucei is endemic in sub-Saharan Africa, where over 70 million
people and countless livestock are at risk of developing T. brucei infection,
called African sleeping sickness, resulting in economic losses of ~$35 million
from the loss of cattle alone. New drugs for this infection are sorely needed and
scientists are trying to identify essential enzymes in the parasite that can be
targets for new therapies. One possible enzyme target is sphingosine kinase, an
enzyme involved in the synthesis of lipids important for cell surface integrity
and regulation of cell functions. In this study, we found that sphingosine kinase
is essential for normal growth and structure of the parasite, raising the
possibility that it could be a good target for new chemotherapy for sleeping
sickness.
PMID- 26443456
TI - What's in a Name? ISSwi1 Corresponds to Transposons Related to Tn2 and Tn3.
PMID- 26443457
TI - Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of
a Newly Emerged Clade of emm89 Streptococcus pyogenes.
AB - Strains of emm89 Streptococcus pyogenes have become one of the major causes of
invasive infections worldwide in the last 10 years. We recently sequenced the
genome of 1,125 emm89 strains and identified three major phylogenetic groups,
designated clade 1, clade 2, and the epidemic clade 3. Epidemic clade 3 strains,
which now cause the great majority of infections, have two distinct genetic
features compared to clade 1 and clade 2 strains. First, all clade 3 organisms
have a variant 3 nga promoter region pattern, which is associated with increased
production of secreted cytolytic toxins SPN (S. pyogenes NADase) and SLO
(streptolysin O). Second, all clade 3 strains lack the hasABC locus mediating
hyaluronic acid capsule synthesis, whereas this locus is intact in clade 1 and
clade 2 strains. We constructed isogenic mutant strains that produce different
levels of SPN and SLO toxins and capsule (none, low, or high). Here we report
that emm89 strains with elevated toxin production are significantly more virulent
than low-toxin producers. Importantly, we also show that capsule production is
dispensable for virulence in strains that already produce high levels of SPN and
SLO. Our results provide new understanding about the molecular mechanisms
contributing to the rapid emergence and molecular pathogenesis of epidemic clade
3 emm89 S. pyogenes. IMPORTANCE: S. pyogenes (group A streptococcus [GAS]) causes
pharyngitis ("strep throat"), necrotizing fasciitis, and other human infections.
Serious infections caused by emm89 S. pyogenes strains have recently increased in
frequency in many countries. Based on whole-genome sequence analysis of 1,125
strains recovered from patients on two continents, we discovered that a new emm89
clone, termed clade 3, has two distinct genetic features compared to its
predecessors: (i) absence of the genes encoding antiphagocytic hyaluronic acid
capsule virulence factor and (ii) increased production of the secreted cytolytic
toxins SPN and SLO. emm89 S. pyogenes strains with the clade 3 phenotype (absence
of capsule and high expression of SPN and SLO) are highly virulent in mice. These
findings provide new understanding of how new virulent clones emerge and cause
severe infections worldwide. This newfound knowledge of S. pyogenes virulence can
be used to help understand future epidemics and conduct new translational
research.
PMID- 26443459
TI - A comment on the AAM track.
PMID- 26443458
TI - Development of protective inflammation and cell-mediated immunity against
Cryptococcus neoformans after exposure to hyphal mutants.
AB - Morphological switch is tightly coupled with the pathogenesis of many dimorphic
fungal pathogens. Cryptococcus neoformans, the major causative agent of
cryptococcal meningitis, mostly presents as the yeast form but is capable of
switching to the hyphal form. The filamentous form has long been associated with
attenuated virulence, yet the underlying mechanism remains elusive. We previously
identified the master regulator Znf2 that controls the yeast-to-hypha transition
in Cryptococcus. Activation of Znf2 promotes hyphal formation and abolishes
fungal virulence in vivo. Here we demonstrated that the cryptococcal strain
overexpressing ZNF2 elicited strong and yet temporally confined proinflammatory
responses in the early stage of infection. In contrast, exacerbated inflammation
in mice infected with the wild-type (WT) strain showed that they were unable to
control the infection. Animals inoculated with this filamentous Cryptococcus
strain had fewer pulmonary eosinophils and CD11c(+) CD11b(+) cells than animals
inoculated with WT yeast. Moreover, mice infected with this strain developed
protective Th1- or Th17-type T cell responses. These findings suggest that the
virulence attenuation of the filamentous form is likely due to its elicitation of
protective host responses. The antivirulence effect of Znf2 was independent of
two previously identified factors downstream of Znf2. Interestingly, mucosal
immunizations with high doses of ZNF2-overexpressing cells, either in the live or
heat-killed form, offered 100% protection to the host from a subsequent challenge
with the otherwise lethal clinical strain H99. Our results demonstrate that heat
resistant cellular components presented in cryptococcal cells with activated ZNF2
elicit protective host immune responses. These findings could facilitate future
research on novel immunological therapies. IMPORTANCE: Cryptococcal meningitis is
one of the leading causes of death among AIDS patients. This disease presents a
severe threat to public health. The current antifungal regimens are
unsatisfactory in controlling or clearing the pathogen Cryptococcus neoformans.
Immunotherapies and/or vaccines could be a promising approach to prevent or
manage this deadly disease. However, the lack of understanding of host-pathogen
interactions during cryptococcal infection greatly hampers the development of
effective immunotherapies. In this study, we discovered that inoculation of
cryptococcal cells with activated Znf2, a morphogenesis regulator and an
antivirulence factor, could shift the host pathological Th2 responses to the
protective Th1 or Th17 responses. Importantly, we discovered that vaccination
with either the viable or heat-killed form of ZNF2-overexpressing cells protected
animals from the otherwise lethal infection by the highly virulent clinical
strain. Our study suggests that the fungal cellular component(s) of the ZNF2
overexpressing strain may provide potential vaccine candidate(s) for controlling
the fatal disease.
PMID- 26443460
TI - Plasmodium falciparum-infected erythrocyte knob density is linked to the PfEMP1
variant expressed.
AB - Members of the clonally variant Plasmodium falciparum erythrocyte membrane
protein 1 (PfEMP1) family mediate adhesion of infected erythrocytes (IEs) to
vascular receptors. PfEMP1 expression is normally confined to nanoscale knob
protrusions on the IE surface membrane. To investigate the relationship between
the densities of these IE surface knobs and the PfEMP1 variant expressed, we used
specific antibody panning to generate three sublines of the P. falciparum clone
IT4, which expresses the PfEMP1 variants IT4VAR04, IT4VAR32b, and IT4VAR60. The
knob density in each subline was then determined by atomic force microscopy (AFM)
and scanning electron microscopy (SEM) and compared to PfEMP1 and knob-associated
histidine-rich protein (KAHRP) expression. Selection for uniform expression of
IT4VAR04 produced little change in knob density, compared to unselected IEs. In
contrast, selection for IT4VAR32b expression increased knob density approximately
3-fold, whereas IEs selected for IT4VAR60 expression were essentially knobless.
When IT4VAR60(+) IEs were subsequently selected to express IT4VAR04 or IT4VAR32b,
they again displayed low and high knob densities, respectively. All sublines
expressed KAHRP regardless of the PfEMP1 expressed. Our study documents for the
first time that knob density is related to the PfEMP1 variant expressed. This may
reflect topological requirements to ensure optimal adhesive properties of the
IEs. IMPORTANCE: Infections with Plasmodium falciparum malaria parasites are
still responsible for many deaths, especially among children and pregnant women.
New interventions are needed to reduce severe illness and deaths caused by this
malaria parasite. Thus, a better understanding of the mechanisms behind the
pathogenesis is essential. A main reason why Plasmodium falciparum malaria is
more severe than disease caused by other malaria species is its ability to
express variant antigens on the infected erythrocyte surface. These antigens are
presented on membrane protrusions known as knobs. This study set out to
investigate the interplay between different variant antigens on the surface of P.
falciparum-infected erythrocytes and the density of the knobs on which the
antigens are expressed. Such a direct analysis of this relationship has not been
reported before but adds to the important understanding of the complexity of
malaria antigen presentation.
PMID- 26443461
TI - HIV inhibition by lactobacilli: easier in a test tube than in real life.
AB - A lactobacillus-dominant vaginal microbiota has been shown to decrease
heterosexual HIV transmission. Nunn et al. now report that a vaginal microbiota
dominated by Lactobacillus crispatus is associated with a relative inability of
HIV pseudoviral particles to transverse cervicovaginal mucus (CVM) in vitro [mBio
6(5):e01084-15, 2015, doi:10.1128/mBio.01084-15]. The purported inhibitory
mechanism is the interaction between carboxyl groups present on HIV and in CVM
that occurred only under acidic conditions when carboxyl groups were protonated.
L. crispatus produces high levels of lactic acid and results in the lowest
vaginal pH when it is the dominant vaginal bacterium. In addition, high levels of
lactic acid inhibit the proliferation of other bacteria that might negatively
affect CVM structure. The utility of enhancing L. crispatus dominance to inhibit
HIV transmission awaits assessment of the influence of ejaculated semen on this
property and investigations on the role of Lactobacillus products such as d
lactic acid in this property.
PMID- 26443462
TI - Erratum for Boudry et al., function of the CRISPR-Cas system of the human
pathogen Clostridium difficile.
PMID- 26443463
TI - Subassemblies and asymmetry in assembly of herpes simplex virus procapsid.
AB - The herpes simplex virus 1 (HSV-1) capsid is a massive particle (~200 MDa; 1,250
A diameter) with T=16 icosahedral symmetry. It initially assembles as a procapsid
with ~4,000 protein subunits of 11 different kinds. The procapsid undergoes major
changes in structure and composition as it matures, a process driven by
proteolysis and expulsion of the internal scaffolding protein. Assembly also
relies on an external scaffolding protein, the triplex, an alpha2beta
heterotrimer that coordinates neighboring capsomers in the procapsid and becomes
a stabilizing clamp in the mature capsid. To investigate the mechanisms that
regulate its assembly, we developed a novel isolation procedure for the
metastable procapsid and collected a large set of cryo-electron microscopy data.
In addition to procapsids, these preparations contain maturation intermediates,
which were distinguished by classifying the images and calculating a three
dimensional reconstruction for each class. Appraisal of the procapsid structure
led to a new model for assembly; in it, the protomer (assembly unit) consists of
one triplex, surrounded by three major capsid protein (MCP) subunits. The model
exploits the triplexes' departure from 3-fold symmetry to explain the highly
skewed MCP hexamers, the triplex orientations at each 3-fold site, and the T=16
architecture. These observations also yielded new insights into maturation.
IMPORTANCE: This paper addresses the molecular mechanisms that govern the self
assembly of large, structurally complex, macromolecular particles, such as the
capsids of double-stranded DNA viruses. Although they may consist of thousands of
protein subunits of many different kinds, their assembly is precise, ranking them
among the largest entities in the biosphere whose structures are uniquely defined
to the atomic level. Assembly proceeds in two stages: formation of a precursor
particle (procapsid) and maturation, during which major changes in structure and
composition take place. Our analysis of the HSV procapsid by cryo-electron
microscopy suggests a hierarchical pathway in which multisubunit "protomers" are
the building blocks of the procapsid but their subunits are redistributed into
different subcomplexes upon being incorporated into a nascent procapsid and are
redistributed again in maturation. Assembly is a highly virus-specific process,
making it a potential target for antiviral intervention.
PMID- 26443464
TI - Is it possible? A different approach to creating a universal influenza vaccine.
AB - The best way to combat influenza virus infection is to prevent it. However, the
continual evolution of circulating influenza virus strains and the constant
threat of newly emerging viruses forces the public health community to annually
update seasonal influenza vaccines while stockpiling potential pandemic virus
vaccines. Thus, there is an urgent need to develop a "universal" influenza
vaccine that affords protection against all strains. In their recent article, L.
M. Schwartzman et al. (mBio 6:e01044-15, 2015, doi:10.1128/mBio.01044-15)
demonstrated that intranasal immunization of mice with a cocktail of viral-like
particles (VLPs) expressing distinct influenza virus hemagglutinin (HA) proteins
can broadly protect against infection not only with the same viral strains but
also with unrelated strains. These findings suggest a promising strategy for
developing a broadly protective "universal" influenza vaccine.
PMID- 26443465
TI - Three-dimensional analysis of palatal shape in patients treated with SARME using
traditional and geometric morphometrics.
AB - OBJECTIVES: To demonstrate the advantages of dense surface models in the
evaluation of surgical-assisted rapid maxillary expansion's effect (SARME) on
palatal morphology. Furthermore, we compared the palatal surface before (T1) and
after (T2) therapy with controls. SETTING AND SAMPLE POPULATION: Surgical
assisted rapid maxillary expansion's effect group of 15 adult patients (Le Fort I
and midpalatal sagittal osteotomy, hyrax screw) and 50 adult individuals.
Patients were treated in General Faculty Hospital, Prague. MATERIALS AND METHODS:
Eighty plaster casts were digitized using a three-dimensional laser scanner and
evaluated using traditional and geometric morphometrics. RESULTS: An unpaired
Student's t-test on the controls and the SARME T1 group revealed significant
differences in all width measurements. Between the controls and the SARME T2
group, significant differences were only related to the interdental angle between
the first molars and particularly to the palatal height. The most remarkable
differences between the pre- and post-treatment palatal morphology were a
widening of the dental arch and buccal shift of the lateral teeth associated with
apparent flattening of the alveolar crest. CONCLUSIONS: Dense surface model
provided descriptive visualization of the treatment effect and was helpful in the
evaluation of palatal shape variability including detection of the most difficult
patients. Correction of the dental arch width discrepancy by SARME was
successfully achieved. After therapy, palatal shape variability of most of the
patients was comparable to the variability of the control group.
PMID- 26443466
TI - Comparative analyses of ion release, pH and multispecies biofilm formation
between conventional and bioactive gutta-percha.
AB - AIM: To analyse the effect of commercial and experimental gutta-percha with the
addition of niobium phosphate glass on biofilm formation by oral bacteria from
human dental plaque. Additional pH and elemental release of the materials were
analysed. METHODOLOGY: The multispecies biofilm was grown anaerobically from
plaque bacteria on standardized discs of each material: hydroxyapatite (HA),
gutta-percha pellets (OBT) (Obtura pellets, Shoreline, CT, USA), ProTaper gutta
percha (PTP) (ProTaper Universal Gutta-Percha Points, Dentsply Maillefer,
Ballaigues, Switzerland), EndoSequence BC gutta-percha (GBC) (Brasseler USA,
Savannah, GA, USA), experimental gutta-percha associated with niobium phosphate
glass (GNB) and niobium phosphate glass (NPG). Specimens (n = 5 per group and per
incubation period) were incubated in brain-heart infusion broth for 3, 14 and 30
days, at 37 degrees C, and stained using live/dead viability assay. Images were
analysed by confocal laser scanning microscopy (CLSM) and the total biovolume
(mm3 ), viable bacteria biovolume (mm3 ), and live percentage (%) were
quantified. For pH measurement, specimens of each material (n = 3) were immersed
in phosphate-buffered saline at 37 degrees C, and pH was monitored in multiple
intervals, up to 30 days. For elemental analysis, additional specimens (n = 3)
were immersed in deionized water and elemental release was analysed by ICP-OES
(inductively coupled plasma - optical emission spectrometry) at time intervals of
3, 14 and 30 days. Differences between groups were evaluated by the two-way
analysis of variation (anova) with Tukey's post hoc test (P < 0.05). RESULTS: The
lowest total biovolume at 30 days was found in GNB, GBC and NPG. GNB had the
lowest viable bacteria biovolume (mean value) at 30 days (P < 0.05), and the
lowest live percentage of bacteria at 3 and 30 days (P < 0.05), whilst NPG had
the lowest live percentage at 14 days (P < 0.05). GNB had the highest pH (8.45)
after 30 days (P < 0.05), and the greatest Zn and Na release at all time
intervals (P < 0.05). Both GBC and GNB had significantly higher Ca release at 14
and 30 days. CONCLUSION: GNB and GBC reduced biofilm formation, GNB had the
lowest amount of viable bacteria in biofilms with the highest pH, and high Zn and
Na release values after 30 days.
PMID- 26443467
TI - A highly efficient Mukaiyama-Mannich reaction of N-Boc isatin ketimines and other
active cyclic ketimines using difluoroenol silyl ethers catalyzed by Ph3PAuOTf.
AB - Ph3PAuOTf is identified as a powerful catalyst for the addition of difluoroenol
silyl ethers to N-Boc isatin ketimines and other two kinds of active cyclic
ketimines. This represents the first Au(i)-catalyzed Mukaiyama-Mannich reaction,
and the corresponding non-fluorinated enol silyl ether proves to be even much
more reactive under the same conditions. This method paves the way to the total
synthesis of difluoromethylated analogues of AG-041R, a gastrin/CCK-B receptor
antagonist.
PMID- 26443468
TI - Differences in environmental exposure assignment due to residential mobility
among children with a central nervous system tumor: Texas, 1995-2009.
AB - In epidemiologic studies of childhood cancer, environmental exposures are often
assigned based on either residence at birth or diagnosis without considering the
impact of residential mobility. Therefore, we evaluated residential mobility and
exposure assignment differences to hazardous air pollutants between birth and
diagnosis in children with a central nervous system (CNS) tumor. Children
diagnosed with CNS tumors during 1995-2009 (N=1,196) were identified from the
Texas Cancer Registry. Census tract-level estimates of 1,3-butadiene and benzene
were used to assign quartiles of exposure based on the maternal residence at
birth and the child's residence at diagnosis. Overall, 64% of younger (0-4 years)
children and 79% of older (5-14 years) children moved between birth and
diagnosis. Using mixed-effects ordinal logistic regression, residence at
diagnosis compared to birth did not result in a significant change in exposure
assignment for younger children; however, older children were more likely to be
placed in a lower 1,3-butadiene or benzene exposure quartile based on residence
at diagnosis compared to birth (odds ratio (OR)=0.58, 95% confidence interval
(CI)=0.45-0.76; OR=0.57, 95% CI=0.44-0.75, respectively). In conclusion, while
the majority of children moved between birth and CNS tumor diagnosis, mobility
did not significantly impact 1,3-butadiene and benzene exposure assessment in
younger children.
PMID- 26443469
TI - Soil ingestion rates for children under 3 years old in Taiwan.
AB - Soil and dust ingestion rates by children are among the most critical exposure
factors in determining risks to children from exposures to environmental
contaminants in soil and dust. We believe this is the first published soil
ingestion study for children in Taiwan using tracer element methodology. In this
study, 66 children under 3 years of age were enrolled from Taiwan. Three days of
fecal samples and a 24-h duplicate food sample were collected. The soil and
household dust samples were also collected from children's homes. Soil ingestion
rates were estimated based on silicon (Si) and titanium (Ti). The average soil
ingestion rates were 9.6+/-19.2 mg/day based on Si as a tracer. The estimated
soil ingestion rates based on Si did not have statistically significant
differences by children's age and gender, although the average soil ingestion
rates clearly increased as a function of children's age category. The estimated
soil ingestion rates based on Si was significantly and positively correlated with
the sum of indoor and outdoor hand-to-mouth frequency rates. The average soil
ingestion rates based on Si were generally lower than the results from previous
studies for the US children. Ti may not be a suitable tracer for estimating soil
ingestion rates in Taiwan because the Ti dioxide is a common additive in food. To
the best of our knowledge, this is the first study that investigated the
correlations between soil ingestion rates and mouthing behaviors in Taiwan or
other parts of Asia. It is also the first study that could compare available soil
ingestion data from different countries and/or different cultures. The hand-to
mouth frequency and health habits are important to estimate the soil ingestion
exposure for children. The results in this study are particularly important when
assessing children's exposure and potential health risk from nearby contaminated
soils in Taiwan.
PMID- 26443470
TI - Third Molars on the Internet: A Guide for Assessing Information Quality and
Readability.
AB - BACKGROUND: Directing patients suffering from third molars (TMs) problems to high
quality online information is not only medically important, but also could enable
better engagement in shared decision making. OBJECTIVES: This study aimed to
develop a scale that measures the scientific information quality (SIQ) for online
information concerning wisdom tooth problems and to conduct a quality evaluation
for online TMs resources. In addition, the study evaluated whether a specific
piece of readability software (Readability Studio Professional 2012) might be
reliable in measuring information comprehension, and explored predictors for the
SIQ Scale. METHODS: A cross-sectional sample of websites was retrieved using
certain keywords and phrases such as "impacted wisdom tooth problems" using 3
popular search engines. The retrieved websites (n=150) were filtered. The
retained 50 websites were evaluated to assess their characteristics, usability,
accessibility, trust, readability, SIQ, and their credibility using DISCERN and
Health on the Net Code (HoNCode). RESULTS: Websites' mean scale scores varied
significantly across website affiliation groups such as governmental, commercial,
and treatment provider bodies. The SIQ Scale had a good internal consistency
(alpha=.85) and was significantly correlated with DISCERN (r=.82, P<.01) and
HoNCode (r=.38, P<.01). Less than 25% of websites had SIQ scores above 75%. The
mean readability grade (10.3, SD 1.9) was above the recommended level, and was
significantly correlated with the Scientific Information Comprehension Scale
(r=.45. P<.01), which provides evidence for convergent validity. Website
affiliation and DISCERN were significantly associated with SIQ (P<.01) and
explained 76% of the SIQ variance. CONCLUSION: The developed SIQ Scale was found
to demonstrate reliability and initial validity. Website affiliation, DISCERN,
and HoNCode were significant predictors for the quality of scientific
information. The Readability Studio software estimates were associated with
scientific information comprehensiveness measures.
PMID- 26443471
TI - Potential for community pharmacies to promote rational drug use in Pakistan.
PMID- 26443473
TI - Gliotoxin--bane or boon?
AB - Gliotoxin (GT) is the most important epidithiodioxopiperazine (ETP)-type fungal
toxin. GT was originally isolated from Trichoderma species as an antibiotic
substance involved in biological control of plant pathogenic fungi. A few
isolates of GT-producing Trichoderma virens are commercially marketed for
biological control and widely used in agriculture. Furthermore, GT is long known
as an immunosuppressive agent and also reported to have anti-tumour properties.
However, recent publications suggest that GT is a virulence determinant of the
human pathogen Aspergillus fumigatus. This compound is thus important on several
counts - it has medicinal properties, is a pathogenicity determinant, is a
potential diagnostic marker and is important in biological crop protection. The
present article addresses this paradox and the ecological role of GT. We discuss
the function of GT as defence molecule, the role in aspergillosis and suggest
solutions for safe application of Trichoderma-based biofungicides.
PMID- 26443472
TI - Medical marijuana patient counseling points for health care professionals based
on trends in the medical uses, efficacy, and adverse effects of cannabis-based
pharmaceutical drugs.
AB - The purpose of this report is to present a review of the medical uses, efficacy,
and adverse effects of the three approved cannabis-based medications and ingested
marijuana. A literature review was conducted utilizing key search terms:
dronabinol, nabilone, nabiximols, cannabis, marijuana, smoke, efficacy, toxicity,
cancer, multiple sclerosis, nausea, vomiting, appetite, pain, glaucoma, and side
effects. Abstracts of the included literature were reviewed, analyzed, and
organized to identify the strength of evidence in medical use, efficacy, and
adverse effects of the approved cannabis-based medications and medical marijuana.
A total of 68 abstracts were included for review. Dronabinol's (Marinol) most
common medical uses include weight gain, chemotherapy-induced nausea and vomiting
(CINV), and neuropathic pain. Nabiximol's (Sativex) most common medical uses
include spasticity in multiple sclerosis (MS) and neuropathic pain. Nabilone's
(Cesamet) most common medical uses include CINV and neuropathic pain. Smoked
marijuana's most common medical uses include neuropathic pain and glaucoma.
Orally ingested marijuana's most common medical uses include improving sleep,
reducing neuropathic pain, and seizure control in MS. In general, all of these
agents share similar medical uses. The reported adverse effects of the three
cannabis-based medications and marijuana show a major trend in central nervous
system (CNS)-related adverse effects along with cardiovascular and respiratory
related adverse effects. Marijuana shares similar medical uses with the approved
cannabis-based medications dronabinol (Marinol), nabiximols (Sativex), and
nabilone (Cesamet), but the efficacy of marijuana for these medical uses has not
been fully determined due to limited and conflicting literature. Medical
marijuana also has similar adverse effects as the FDA-approved cannabis-based
medications mainly consisting of CNS related adverse effects but also including
cardiovascular and respiratory related adverse effects. Finally, insufficient
higher-order evidence to support the widespread use of medical marijuana was
found, but a limited amount of moderate-level evidence supports its use in pain
and seizure management.
PMID- 26443474
TI - Virus-resembling nano-structures for near infrared fluorescence imaging of
ovarian cancer HER2 receptors.
AB - Ovarian cancer remains the dominant cause of death due to malignancies of the
female reproductive system. The capability to identify and remove all tumors
during intraoperative procedures may ultimately reduce cancer recurrence, and
lead to increased patient survival. The objective of this study is to investigate
the effectiveness of an optical nano-structured system for targeted near infrared
(NIR) imaging of ovarian cancer cells that over-express the human epidermal
growth factor receptor 2 (HER2), an important biomarker associated with ovarian
cancer. The nano-structured system is comprised of genome-depleted plant
infecting brome mosaic virus doped with NIR chromophore, indocyanine green, and
functionalized at the surface by covalent attachment of monoclonal antibodies
against the HER2 receptor. We use absorption and fluorescence spectroscopy, and
dynamic light scattering to characterize the physical properties of the
constructs. Using fluorescence imaging and flow cytometry, we demonstrate the
effectiveness of these nano-structures for targeted NIR imaging of HER2 receptors
in vitro. These functionalized nano-materials may provide a platform for NIR
imaging of ovarian cancer.
PMID- 26443475
TI - Cannabinoids in paediatric neurology.
PMID- 26443476
TI - Audiometric Outcomes in Pediatric Temporal Bone Trauma.
AB - OBJECTIVE: To characterize pediatric temporal bone trauma, focusing on
audiometric outcomes. STUDY DESIGN: Case series with chart review. SETTING:
Tertiary care children's hospital. SUBJECTS AND METHODS: Cases were reviewed of
children (<18 years) presenting over a 3-year period with computed tomography
proven temporal bone fracture and audiology examination. All scans were read by a
neuroradiologist and reviewed by a pediatric otolaryngologist. Demographics,
fracture pattern, and audiometric data were recorded. RESULTS: Fifty-eight
patients (60 fractures) met inclusion criteria. The majority (93%) were otic
capsule-sparing fractures. The types and severity of hearing loss were
significantly different between the 2 fracture patterns. Based on pure-tone
average, all otic capsule-violating fractures had abnormal initial audiograms;
75% of these losses were severe. Approximately half (54%) of otic capsule-sparing
fractures had abnormal initial audiograms; a majority were mild losses (85%). All
classifiable losses in otic capsule-violating cases were of mixed type, whereas
the majority (75%) of losses in otic capsule-sparing cases were conductive.
Regardless of classification, 72% of patients with otic capsule-sparing fractures
and initially abnormal audiograms improved to normal levels at a mean of 48 days
posttrauma; this increased to 83% when only conductive losses were considered.
CONCLUSIONS: Hearing loss type and severity differ in otic capsule-sparing and
otic capsule-violating temporal bone fractures. A majority of children with otic
capsule-sparing fractures and associated hearing loss improve to normal levels in
about 6 weeks, especially if the original loss is classified as solely
conductive. Children who do not improve within this time frame may warrant early
investigation into surgically correctable causes.
PMID- 26443477
TI - Office Insertion of Tympanostomy Tubes without Anesthesia in Young Children.
PMID- 26443478
TI - Impact of Diabetes Mellitus on Head and Neck Cancer Patients Undergoing Surgery.
AB - OBJECTIVE: The impact of diabetes mellitus (DM) on surgical outcomes and cost of
care for patients undergoing surgery for head and neck cancer (HNCA) is not well
established. We used the Nationwide Inpatient Sample to analyze the postoperative
impact of DM on HNCA patients. STUDY DESIGN: Population-based inpatient registry
analysis. SETTING: Academic medical center. SUBJECTS AND METHODS: Discharge data
from the Nationwide Inpatient Sample were analyzed for patients undergoing HNCA
surgery from 2002 to 2010. Patient demographics, comorbidities, length of stay,
hospital charges, and postoperative complications were compared between HNCA
patients with and without DM. RESULTS: Of 31,075 patients, 4029 patients (13.0%)
had a DM diagnosis. DM patients were older (65.7 +/- 10.8 vs 61.1 +/- 14.1 years
old; P < .001), had more preexisting comorbidities, had longer hospitalizations,
and incurred greater hospital charges. Compared with the non-DM cohort, DM
patients experienced significantly higher rates of postoperative infections (2.6%
vs 2.1%, P = .025), cardiac events (9.0% vs 4.3%, P < .001), pulmonary
edema/failure (6.6% vs 5.7%, P = .023), acute renal failure (3.3% vs 1.5%, P <
.001), and urinary tract infections (2.8 % vs 2.1%, P = .005). No differences in
surgical wound healing rates were observed (0.1 vs 0.1, P = .794). On
multivariate logistic regression corrected for age and race, DM patients had
greater odds of postoperative infections (1.382, P = .007), cardiac events
(1.893, P < .001), and acute renal failure (2.023, P < .001). CONCLUSIONS: DM is
associated with greater length of stay and hospital charges among HNCA patients.
DM patients have significantly greater rates of postoperative complications,
including postoperative infections, cardiac events, and acute renal failure.
PMID- 26443479
TI - Who Wrote This Clinical Practice Guideline?
AB - The American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical
practice guidelines address a variety of otolaryngologic diseases and/or
procedures. It may seem reasonable to create these guidelines by assembling a
team of expert clinicians familiar with the pertinent clinical issues and the
available evidence, with debate and eventual agreement leading to
recommendations. However, trustworthy clinical practice guidelines are in fact
created via a defined process to assemble a guideline development group composed
of diverse stakeholders: clinician generalists and specialists, content experts,
methodologists, physicians and nonphysicians, patients, and advocates. Such a
guideline development group can create a valuable and trusted guideline for
clinicians and affected patients.
PMID- 26443480
TI - Genetic Alterations in Gliosarcoma and Giant Cell Glioblastoma.
AB - The majority of glioblastomas develop rapidly with a short clinical history
(primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress
from diffuse astrocytoma or anaplastic astrocytoma. IDH mutations are the genetic
hallmark of secondary glioblastomas. Gliosarcomas and giant cell glioblastomas
are rare histological glioblastoma variants, which usually develop rapidly. We
determined the genetic patterns of 36 gliosarcomas and 19 giant cell
glioblastomas. IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in
18 of 19 giant cell glioblastomas analyzed, indicating that they are histological
variants of primary glioblastoma. Furthermore, LOH 10q (88%) and TERT promoter
mutations (83%) were frequent in gliosarcomas. Copy number profiling using the
450k methylome array in 5 gliosarcomas revealed CDKN2A homozygous deletion (3
cases), trisomy chromosome 7 (2 cases), and monosomy chromosome 10 (2 cases).
Giant cell glioblastomas had LOH 10q in 50% and LOH 19q in 42% of cases. ATRX
loss was detected immunohistochemically in 19% of giant cell glioblastomas, but
absent in 17 gliosarcomas. These and previous results suggest that gliosarcomas
are a variant of, and genetically similar to, primary glioblastomas, except for a
lack of EGFR amplification, while giant cell glioblastoma occupies a hybrid
position between primary and secondary glioblastomas.
PMID- 26443481
TI - Validation of a five-factor model of a Chinese Mandarin version of the Positive
and Negative Syndrome Scale (CMV-PANSS) in a sample of 813 schizophrenia
patients.
AB - OBJECTIVES: The Positive and Negative Syndrome Scale (PANSS) is one of the most
widely used instruments for measuring the severity of schizophrenia. However,
until now, there has not been a published, validated Chinese Mandarin version of
the five-factor model PANSS with confirmatory factor analysis (CFA) for
schizophrenic patients in Taiwan. METHODS: A total of 813 subjects were
recruited. Internal consistency was evaluated with Cronbach's alpha coefficient.
For test re-test reliability, 57 patients were reassessed and intra-class
correlation coefficients were calculated. For validity, exploratory factor
analysis (EFA) and confirmatory factor analysis (CFA) using a Structured Equation
Model were implemented to identify the factor model. RESULTS: The Cronbach's
alpha coefficient was 0.928. The intra-class coefficient was 0.878 (95% CI: 0.79
0.92). The final model was composed of five factors. EFA explained a total of
64.2% of the variance. CFA indicated a good fitting model. Except for the PANSS
items G7 (motor retardation), G8 (uncooperativeness), N5 (abstract thinking), and
G10 (disorientation), this study found that the items loaded on these factors
were similar to the consensus items published in prior studies. CONCLUSIONS: In
summary, these findings support the Chinese Mandarin version of the PANSS as a
reliable and valid instrument for the assessment of the severity of
psychopathology in hospitalized, stable patients with schizophrenia. More
effective and specific treatment models targeting sub-culture differences are
expected to be developed in future studies.
PMID- 26443482
TI - Primary and secondary alterations of white matter connectivity in schizophrenia:
A study on first-episode and chronic patients using whole-brain tractography
based analysis.
AB - Schizophrenia is a debilitating mental disorder that is associated with an
impaired connection of cerebral white matter. Studies on patients with chronic
and first-episode schizophrenia have found widespread white matter abnormalities.
However, it is unclear whether the altered connections are inherent in or
secondary to the disease. Here, we sought to identify white matter tracts with
altered connections and to distinguish primary or secondary alterations among 74
fiber tracts across the whole brain using an automatic tractography-based
analysis method. Thirty-one chronic, 25 first-episode patients with schizophrenia
and 31 healthy controls were recruited to receive diffusion spectrum magnetic
resonance imaging at 3T. Seven tracts were found to exhibit significant
differences between the groups; they included the right arcuate fasciculus,
bilateral fornices, left superior longitudinal fasciculus I, and fibers of the
corpus callosum to the bilateral dorsolateral prefrontal cortices (DLPFC),
bilateral temporal poles, and bilateral hippocampi. Post-hoc between-group
analyses revealed that the connection of the callosal fibers to the bilateral
DLPFC was significantly decreased in chronic patients but not in first-episode
patients. In a stepwise regression analysis, the decline of the tract connection
was significantly predicted by the duration of illness. In contrast, the
remaining six tracts showed significant alterations in both first-episode and
chronic patients and did not associate with clinical variables. In conclusion,
reduced white matter connectivity of the callosal fibers to the bilateral DLPFC
may be a secondary change that degrades progressively in the chronic stage,
whereas alterations in the other six tracts may be inherent in the disease.
PMID- 26443483
TI - Volatile Organic Metabolites Identify Patients with Mesangial Proliferative
Glomerulonephritis, IgA Nephropathy and Normal Controls.
AB - Urinary volatile organic compounds (VOCs) analysis for kidney diseases has
attracted a large amount of scientific interest recently, and urinary metabolite
analysis has already been applied to many diseases. Urine was collected from 15
mesangial proliferative glomerulonephritis (MsPGN) patients, 21 IgA nephropathy
(IgAN) patients and 15 healthy controls. Solid phase microextraction
chromatography- mass spectrometry (SPME-GC-MS) was used to analyse the urinary
metabolites. The statistical methods principal component analysis (PCA) and
orthogonal partial least-squares discriminant analysis (OPLSDA) were performed to
process the final data. Five metabolites were significantly greater in the group
of MsPGN patients than in the normal control group (P < 0.05) while three
metabolites were found at increased levels in the group of IgAN patients compared
with the normal controls (P < 0.05). In addition, five metabolites were
significantly increased in the group of IgAN patients compared with the MsPGN
patients (P < 0.05). These five metabolites may be specific biomarkers for
distinguishing between MsPGN and IgAN. The analysis of urinary VOCs appears to
have potential clinical applications as a diagnostic tool.
PMID- 26443484
TI - Reduced occurrence of ventilator-associated pneumonia after cardiac surgery using
preoperative 0.2% chlorhexidine oral rinse: results from a single-centre single
blinded randomized trial.
AB - Since mechanical ventilation after cardiac surgery increases the risk of
ventilator-associated pneumonia (VAP), we conducted a prospective randomized
controlled trial to investigate the effect of preoperative 0.2% chlorhexidine on
postoperative VAP. Ninety-four patients scheduled for heart surgery were
randomized to a chlorhexidine group (N = 47) or control (saline) group (N = 47).
On the day before surgery, patients gargled three times with 0.2% chlorhexidine
or saline 30 min after each meal and 5 min after teeth brushing at bedtime. VAP
occurred in 8.5% of the chlorhexidine group and in 23.4% of the controls.
Preoperative chlorhexidine mouthwash reduced the incidence of postoperative VAP
significantly.
PMID- 26443485
TI - Effectiveness of meticillin-resistant Staphylococcus aureus decolonization in
long-term haemodialysis patients: a systematic review and meta-analysis.
AB - BACKGROUND: Chronic haemodialysis patients are a high-risk population for
meticillin-resistant Staphylococcus aureus (MRSA) colonization, which is a
precursor of infection. AIM: To summarize the effect of nasal (+/- whole-body
wash) MRSA decolonization in haemodialysis patients by means of a systematic
review and meta-analysis. METHODS: We identified eligible studies using Medline,
Embase, the Cochrane database, clinicaltrials.org, and conference abstracts
investigating the success of MRSA decolonization in haemodialysis patients. For
the statistical analysis, we used Stata 13 to express study-specific proportions
with 95% confidence intervals. A likelihood ratio test was used to assess inter
study heterogeneity. FINDINGS: Six published prospective cohort studies and one
study described in a conference abstract met our inclusion criteria. From 1150
haemodialysis patients enrolled in these studies, MRSA was isolated from nasal
swabs of 147 (12.8%) patients. Six of the trials used mupirocin nasal ointment
and combined it with chlorhexidine body washes for decolonization. The most
widely used protocol was a five-day course of mupirocin nasal ointment
application three times a day, and chlorhexidine body wash once daily. The pooled
success rate of decolonization was 0.88 (95% confidence interval: 0.75-0.95). A
likelihood ratio test of the fixed versus the random-effects model showed
significant inter-study heterogeneity (P = 0.047). Four of seven studies
determined subsequent MRSA infections in 94 carriers overall, two (2%) of which
experienced infection. CONCLUSION: The use of mupirocin together with whole-body
decolonization is highly effective in eradicating MRSA carriage in haemodialysis
patients. The current literature, however, is characterized by a lack of
comparative effectiveness studies for this intervention.
PMID- 26443486
TI - Development and evaluation of the Turkish matrix sentence test.
AB - OBJECTIVES: The Turkish matrix sentence test, TURMatrix, was developed for
precise, internationally comparable speech intelligibility testing. DESIGN: The
TURMatrix comprises a base matrix of ten well-known Turkish names, numbers,
adjectives, objects, verbs, from which syntactically fixed sentences were
randomly composed. Test conduction may be in an open-set (standard), or closed
set response format. Homogeneity in intelligibility of the test material was
optimized by applying level adaptations (maximal +/- 3 dB) based on word-specific
speech reception thresholds (SRTs). Test list equivalence was verified and
reference values were determined. STUDY SAMPLE: Thirty-eight native listeners of
Turkish with normal hearing. RESULTS: After training, mean SRT and slope of the
final test lists were -8.3 +/- 0.2 dB SNR and 14.1 +/- 1.0%/dB, respectively
(fixed SNR measurements; inter-list variability). For adaptive measurements,
average across listeners was -7.2 +/- 0.7 dB SNR in the open-set and -7.9 +/- 0.7
dB SNR in the closed-set response format. Mean SRT for adaptive measurements in
the open-set response format in quiet was 20.3 +/- 4.1 dB. Individual SRTs in
quiet correlated more closely with audiograms than with SRTs in noise.
CONCLUSIONS: The TURMatrix was developed according to European standards and
provides reliable speech intelligibility measurements in noise and quiet.
PMID- 26443488
TI - Management of Children with Unilateral Hearing Loss.
AB - Children with impaired hearing in one ear (unilateral hearing loss [UHL]) and
normal hearing in the other ear experience challenges in understanding speech in
noisy backgrounds and localizing the source of sounds in 3-dimensional space.
They are at a high risk for speech and language delay and need educational help
in school. However, definitive evidence of benefit from amplification is
currently lacking to recommend placement of hearing aids or cochlear implants in
all young children with UHL. Management of UHL in children should be guided by
the child's development, performance in school, and personal/family values and
preferences.
PMID- 26443487
TI - Genetics of Hearing Loss: Syndromic.
AB - Hearing loss (HL) is one of the most common birth defects in developed countries
and is a diverse pathologic condition with different classifications. One of
these is based on the association with other clinical features, defined as
syndromic hearing loss (SHL). Determining the cause of the HL in these patients
is extremely beneficial as it enables a personalized approach to caring for the
individual. Early screening can further aid in optimal rehabilitation for a
child's development and growth. The advancement of high-throughput sequencing
technology is facilitating rapid and low-cost diagnostics for patients with SHL.
PMID- 26443489
TI - Communication Assessment and Intervention: Implications for Pediatric Hearing
Loss.
AB - Historically, children with hearing loss have fallen well behind their hearing
peers in the areas of speech and language development, which has often limited
their participation in a range of social, educational, and vocational activities.
However, with early identification and appropriate intervention coupled with
current hearing technology, children with hearing loss can achieve speech and
language milestones at rates commensurate with hearing peers. To attain the best
outcomes for these children, an early intervention system that provides thorough
and unbiased information to families and allows for the efficient and coordinated
efforts of qualified professionals must be present.
PMID- 26443491
TI - Prospective gait changes as a function of shifting perceptions of slipperiness:
effects of visual and somatosensory cues.
AB - Forty participants, ages 18-45 years, rated perceived slipperiness before and
after walking on five different floors under three different surface conditions.
The before-ratings were taken as a proxy for visual cues to slipperiness, while
after-ratings were taken as a proxy for somatosensory feedback received while
walking on the surface. Before and after ratings of slipperiness were used to
predict gait parameters, as a function of trial, during repeated walking. Effects
of after-ratings of slipperiness were observed beginning on the second trial, and
continued through the fifth trial, while effects of before-ratings of
slipperiness were most apparent on the first trial. When perceived slipperiness
increased (or decreased) from before to after walking on the surface, gait became
more (or less) protective across trials. It is concluded that both visual cues,
as well as somatosensory feedback, are used in the prospective control of gait.
Practitioner Summary: Effects of visual and somatosensory cues to slipperiness on
gait were disentangled using floor surfaces varying in the slipperiness suggested
by those cues. Visually based ratings of slipperiness predicted gait parameters
on earlier trials, while somatosensory-based ratings predicted gait parameters on
subsequent trials. Flooring design should provide reliable information regarding
slipperiness.
PMID- 26443490
TI - On the Horizon: Cochlear Implant Technology.
AB - Cochlear implantation and cochlear implants (CIs) have a long history filled with
innovations that have resulted in the high-performing device's currently
available. Several promising technologies have been reviewed in this article,
which hold the promise to drive performance even higher. Remote CI programming,
totally implanted devices, improved neural health and survival through targeted
drug therapy and delivery, intraneural electrode placement, electroacoustical
stimulation and hybrid CIs, and methods to enhance the neural-prosthesis
interface are evolving areas of innovation reviewed in this article.
PMID- 26443492
TI - On the self-damping nature of densification in photonic sintering of
nanoparticles.
AB - Sintering of nanoparticle inks over large area-substrates is a key enabler for
scalable fabrication of patterned and continuous films, with multiple emerging
applications. The high speed and ambient condition operation of photonic
sintering has elicited significant interest for this purpose. In this work, we
experimentally characterize the temperature evolution and densification in
photonic sintering of silver nanoparticle inks, as a function of nanoparticle
size. It is shown that smaller nanoparticles result in faster densification, with
lower temperatures during sintering, as compared to larger nanoparticles.
Further, high densification can be achieved even without nanoparticle melting.
Electromagnetic Finite Element Analysis of photonic heating is coupled to an
analytical sintering model, to examine the role of interparticle neck growth in
photonic sintering. It is shown that photonic sintering is an inherently self
damping process, i.e., the progress of densification reduces the magnitude of
subsequent photonic heating even before full density is reached. By accounting
for this phenomenon, the developed coupled model better captures the
experimentally observed sintering temperature and densification as compared to
conventional photonic sintering models. Further, this model is used to uncover
the reason behind the experimentally observed increase in densification with
increasing weight ratio of smaller to larger nanoparticles.
PMID- 26443494
TI - Editorial Comment to Urinary tract infection-like symptom is associated with
worse bladder cancer outcomes in the Medicare population: Implications for sex
disparities.
PMID- 26443493
TI - Stepped care versus standard trauma-focused cognitive behavioral therapy for
young children.
AB - BACKGROUND: To compare the effectiveness and cost of stepped care trauma-focused
cognitive behavioral therapy (SC-TF-CBT), a new service delivery method designed
to address treatment barriers, to standard TF-CBT among young children who were
experiencing posttraumatic stress symptoms (PTSS). METHODS: A total of 53
children (ages 3-7 years) who were experiencing PTSS were randomly assigned (2:1)
to receive SC-TF-CBT or TF-CBT. Assessments by a blinded evaluator occurred at
screening/baseline, after Step One for SC-TF-CBT, posttreatment, and 3-month
follow-up. TRIAL REGISTRATION: ClinicalTrials.gov:
https://www.clinicaltrials.gov/ct2/show/NCT01603563. RESULTS: There were
comparable improvements over time in PTSS and secondary outcomes in both
conditions. Noninferiority of SC-TF-CBT compared to TF-CBT was supported for the
primary outcome of PTSS, and the secondary outcomes of severity and internalizing
symptoms, but not for externalizing symptoms. There were no statistical
differences in comparisons of changes over time from pre- to posttreatment and
pre- to 3-month follow-up for posttraumatic stress disorder diagnostic status,
treatment response, or remission. Parent satisfaction was high for both
conditions. Costs were 51.3% lower for children in SC-TF-CBT compared to TF-CBT.
CONCLUSIONS: Although future research is needed, preliminary evidence suggests
that SC-TF-CBT is comparable to TF-CBT, and delivery costs are significantly less
than standard care. SC-TF-CBT may be a viable service delivery system to address
treatment barriers.
PMID- 26443495
TI - Evaluating Guideline-recommended Pain Medication Use Among Patients with Newly
Diagnosed Fibromyalgia.
AB - OBJECTIVES: To compare pain medication treatment changes across cohorts of newly
diagnosed patients with fibromyalgia (FM) treated with guideline-recommended
medications or opioids. METHODS AND DESIGN: Retrospective claims data analysis
examined adult commercial health plan members newly diagnosed with FM (initial
diagnosis = index date) from January 2008 to February 2012. Patients had 6-month
pre-index and 12-month postindex periods and received pain medication within 6
months postindex; cohorts were based on the first postindex medication. Guideline
recommended medication cohorts were anti-epileptic drug (AED), serotonin
norepinephrine reuptake inhibitor (SNRI), selective serotonin reuptake inhibitor
(SSRI), and tricyclic antidepressant (TCA). Short-acting and long-acting opioid
(SAO, LAO) cohorts were also identified. Pairwise comparisons with the SAO cohort
were conducted. Cox proportional hazards regressions modeled the likelihood of
receiving guideline-recommended therapy. RESULTS: The final sample was 96,175
patients (mean age 47.3 years; 72.5% female), distributed into SAO (57%), SSRI
(22%), AED (10%), SNRI (6%), TCA (3%), and LAO (2%) cohorts. The SAO cohort had
the most discontinuation (49% vs. 6% to 22%, P < 0.01) and the least augmentation
(29% vs. 35% to 50%, P < 0.01). Regression analyses indicated that patients with
(vs. without) pre-index guideline-recommended medications were 2 to 4 times more
likely to receive them postindex. Patients in the opioid cohorts were about half
as likely to receive subsequent guideline-recommended medications. CONCLUSIONS:
Opioid use was widespread among patients with FM. Once patients received opioids
postdiagnosis, the likelihood of receiving guideline-recommended medications was
small. These real-world results indicate an opportunity may exist for improved FM
management using recommended therapies in clinical practice.
PMID- 26443496
TI - The AbgT family: A novel class of antimetabolite transporters.
AB - The AbgT family of transporters was thought to contribute to bacterial folate
biosynthesis by importing the catabolite p-aminobenzoyl-glutamate for producing
this essential vitamin. Approximately 13,000 putative transporters of the family
have been identified. However, before our work, no structural information was
available and even functional data were minimal for this family of membrane
proteins. To elucidate the structure and function of the AbgT family of
transporters, we recently determined the X-ray structures of the full-length
Alcanivorax borkumensis YdaH and Neisseria gonorrhoeae MtrF membrane proteins.
The structures reveal that these two transporters assemble as dimers with
architectures distinct from all other families of transporters. Both YdaH and
MtrF are bowl-shaped dimers with a solvent-filled basin extending from the
cytoplasm halfway across the membrane bilayer. The protomers of YdaH and MtrF
contain nine transmembrane helices and two hairpins. These structures directly
suggest a plausible pathway for substrate transport. A combination of the crystal
structure, genetic analysis and substrate accumulation assay indicates that both
YdaH and MtrF behave as exporters, capable of removing the folate metabolite p
aminobenzoic acid from bacterial cells. Further experimental data based on drug
susceptibility and radioactive transport assay suggest that both YdaH and MtrF
participate as antibiotic efflux pumps, importantly mediating bacterial
resistance to sulfonamide antimetabolite drugs. It is possible that many of these
AbgT-family transporters act as exporters, thereby conferring bacterial
resistance to sulfonamides. The AbgT-family transporters may be important targets
for the rational design of novel antibiotics to combat bacterial infections.
PMID- 26443497
TI - Heat shock protein 20 (HSP20) is a novel substrate for protein kinase D1 (PKD1).
AB - Heat shock protein 20 (HSP20) has cardioprotective qualities, which are triggered
by PKA phosphorylation. PKD1 is also a binding partner for HSP20, and this
prompted us to investigate whether the chaperone was a substrate for PKD1. We
delineate the PKD1 binding sites on HSP20 and show for the first time HSP20 is a
substrate for PKD1. Phosphorylation of HSP20 by PKD1 is diminished by
pharmacological or siRNA reduction of PKD1 activity and is enhanced following
PKD1 activation. Our results suggest that both PKA and PKD1 can both
phosphorylate HSP20 on serine 16 but that PKA is the most dominant.
PMID- 26443498
TI - 2014 CODEPEH recommendations: Early detection of late onset deafness,
audiological diagnosis, hearing aid fitting and early intervention.
AB - The latest scientific literature considers early diagnosis of deafness as the key
element to define the educational and inclusive prognosis of the deaf child,
because it allows taking advantage of the critical period of development (0-4
years). Highly significant differences exist between deaf people who have been
stimulated early and those who have received late or improper intervention. Early
identification of late-onset disorders requires special attention and knowledge
on the part of every childcare professional. Programs and additional actions
beyond neonatal screening should be designed and planed to ensure that every
child with a significant hearing loss is detected early. For this purpose, the
CODEPEH would like to highlight the need for continuous monitoring of children's
auditory health. Consequently, CODEPEH has drafted the recommendations included
in the present document.
PMID- 26443499
TI - Diversity-oriented synthesis of tetrathia[8]circulenes by sequential C-H
borylation and annulation.
AB - We have succeeded in the diversity-oriented synthesis of tetrathia[8]circulenes
by sequential C-H borylation and annulation from cyclic tetrathiophene, and time
resolved microwave conductivity studies have proved that the intrinsic hole
mobilities of tetrathia[8]circulenes are dependent on the chain length of the
alkyl substituents at the peripheral positions.
PMID- 26443500
TI - One-Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides.
AB - A general and efficient one-pot aminoethylation of substituted indoles/pyrroles
was accomplished for the synthesis of various tryptamine derivatives employing a
combination of alkynes and sulfonyl azides as readily accessible aminoethylating
agents. The reaction features a successful integration of copper-catalyzed alkyne
and azide cycloaddition to N-sulfonyl-1,2,3-triazole, rhodium-catalyzed selective
insertion of alpha-iminocarbenes onto the C3-H bond of indoles, and reduction of
the resultant enamides to tryptamine derivatives employing either NaCNBH3 or
palladium catalyst, in one-pot. The reaction also showed excellent functional
group tolerance and allowed the synthesis of various substituted tryptamines in
good to excellent yield. This transformation constitutes a one-pot formal
regioselective functionalization of terminal alkynes. Utility of the synthesized
tryptamine was further demonstrated in the synthesis of dihydro-beta-carboline
and tryptoline.
PMID- 26443501
TI - Finding cannabinoids in hair does not prove cannabis consumption.
AB - Hair analysis for cannabinoids is extensively applied in workplace drug testing
and in child protection cases, although valid data on incorporation of the main
analytical targets, ?9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-THC (THC
COOH), into human hair is widely missing. Furthermore, ?9-tetrahydrocannabinolic
acid A (THCA-A), the biogenetic precursor of THC, is found in the hair of persons
who solely handled cannabis material. In the light of the serious consequences of
positive test results the mechanisms of drug incorporation into hair urgently
need scientific evaluation. Here we show that neither THC nor THCA-A are
incorporated into human hair in relevant amounts after systemic uptake. THC-COOH,
which is considered an incontestable proof of THC uptake according to the current
scientific doctrine, was found in hair, but was also present in older hair
segments, which already grew before the oral THC intake and in sebum/sweat
samples. Our studies show that all three cannabinoids can be present in hair of
non-consuming individuals because of transfer through cannabis consumers, via
their hands, their sebum/sweat, or cannabis smoke. This is of concern for e.g.
child-custody cases as cannabinoid findings in a child's hair may be caused by
close contact to cannabis consumers rather than by inhalation of side-stream
smoke.
PMID- 26443502
TI - The mechanism of water/ion exchange at a protein surface: a weakly bound chloride
in Helicobacter pylori apoflavodoxin.
AB - Binding/unbinding of small ligands, such as ions, to/from proteins influences
biochemical processes such as protein folding, enzyme catalysis or protein/ligand
recognition. We have investigated the mechanism of chloride/water exchange at a
protein surface (that of the apoflavodoxin from Helicobacter pylori) using
classical all-atom molecular dynamics simulations. They reveal a variety of
chloride exit routes and residence times; the latter is related to specific
coordination modes of the anion. The role of solvent molecules in the mechanism
of chloride unbinding has been studied in detail. We see no temporary increase in
chloride coordination along the release process. Instead, the coordination of new
water molecules takes place in most cases after the chloride/protein atom release
event has begun. Moreover, the distribution function of water entrance events
into the first chloride solvation shell peaks after chloride protein atom
dissociation events. All these observations together seem to indicate that water
molecules simply fill the vacancies left by the previously coordinating protein
residues. We thus propose a step-by-step dissociation pathway in which
protein/chloride interactions gradually break down before new water molecules
progressively fill the vacant positions left by protein atoms. As observed for
other systems, water molecules associated with bound chloride or with protein
atoms have longer residence times than those bound to the free anion. The
implications of the exchange mechanism proposed for the binding of the FMN
(Flavin Mononucleotide) protein cofactor are discussed.
PMID- 26443504
TI - The Escherichia coli Hemolysin.
AB - The Escherichia coli hemolysin, earlier referred to as the hemolysin, is the best
characterized repeats in toxin (RTX) secreted by a type I exoprotein secretion
system. The E. coli hemolysin is a significant virulence factor in murine models
of peritonitis and ascending urinary tract infection, which suggests it is likely
to be an important cytotoxin in human, extraintestinal E. coli diseases. Among E.
coli or Salmonella strains there are no known examples of strict RTX leukotoxins
in which lytic activity is limited to white blood cells. The general gene
organization of the Vibrio cholerae RTX locus is similar to that seen with either
of the E. coli hly and ehx loci with C, B, and D RTX homologs, clearly indicating
it is a member of the RTX family. The hemolysin occurs less frequently in
cystitis strains and only rarely among normal fecal strains. Among the
extraintestinal E. coli isolates, the hlyCABDgenes were among the first virulence
factors localized to unique, tRNA-associated segments of E. coli chromosomes. The
hemolysin genes were eventually linked to P-type pilin and cytotoxic necrotizing
factor-1 genes. Recent progress with its study has slowed down because of the
difficulty in deriving the physical structure of the hemolysin protein or other
RTX toxins and establishing its precise cytotoxic mechanism and role in
pathogenesis of extraintestinal E. coli disease. Genomic sequencing has revealed
that there are additional RTX-like genes found among many different pathogens;
perhaps new efforts to discover their functions will aid progress in the RTX
toxin field.
PMID- 26443503
TI - Implicit Theories Relate to Youth Psychopathology, But How? A Longitudinal Test
of Two Predictive Models.
AB - Research shows relations between entity theories-i.e., beliefs that traits and
abilities are unchangeable-and youth psychopathology. A common interpretation has
been that entity theories lead to psychopathology, but another possibility is
that psychopathology predicts entity theories. The two models carry different
implications for developmental psychopathology and intervention design. We tested
each model's plausibility, examining longitudinal associations between entity
theories of thoughts, feelings, and behavior and psychopathology in early
adolescents across one school year (N = 59, 52 % female, ages 11-14, 0 %
attrition). Baseline entity theories did not predict increases in
psychopathology; instead, baseline psychopathology predicted increased entity
theories over time. When symptom clusters were assessed individually, greater
youth internalizing (but not externalizing) problems predicted subsequent
increases in entity theories. Findings suggest that the commonly proposed
predictive model may not be the only one warranting attention. They suggest that
youth psychopathology may contribute to the development of certain kinds of
entity theories.
PMID- 26443505
TI - Glycolysis and Flux Control.
AB - Central metabolism of carbohydrates uses the Embden-Meyerhof-Parnas (EMP),
pentose phosphate (PP), and Entner-Doudoroff (ED) pathways. This review reviews
the biological roles of the enzymes and genes of these three pathways of E. coli.
Glucose, pentoses, and gluconate are primarily discussed as the initial
substrates of the three pathways, respectively. The genetic and allosteric
regulatory mechanisms of glycolysis and the factors that affect metabolic flux
through the pathways are considered here. Despite the fact that a lot of
information on each of the reaction steps has been accumulated over the years for
E. coli, surprisingly little quantitative information has been integrated to
analyze glycolysis as a system. Therefore, the review presents a detailed
description of each of the catalytic steps by a systemic approach. It considers
both structural and kinetic aspects. Models that include kinetic information of
the reaction steps will always contain the reaction stoichiometry and therefore
follow the structural constraints, but in addition to these also kinetic rate
laws must be fulfilled. The kinetic information obtained on isolated enzymes can
be integrated using computer models to simulate behavior of the reaction network
formed by these enzymes. Successful examples of such approaches are the modeling
of glycolysis in S. cerevisiae, the parasite Trypanosoma brucei, and the red
blood cell. With the rapid developments in the field of Systems Biology many new
methods have been and will be developed, for experimental and theoretical
approaches, and the authors expect that these will be applied to E. coli
glycolysis in the near future.
PMID- 26443506
TI - Glycerol and Methylglyoxal Metabolism.
AB - The metabolic connection between glycerol and methylglyoxal (MG) is principally
that DHAP, which is an intermediate in the aerobic breakdown of glycerol, is also
the major precursor of MG, being the substrate for methylglyoxal synthase (MGS).
The synthesis of MG is a consequence of unbalanced metabolism related either to a
limitation for phosphate or to excessive carbon flux through the pathways that
have the capacity to generate significant pools of DHAP. Cells producing MG
produce a poison as an intermediate strategy for survival of metabolic imbalance.
Indeed the panoply of metabolic regulation in this sector of catabolism can be
seen as a strategy to avoid death by self-poisoning. Glycerol entry into
Escherichia coli and Salmonella enterica serovar Typhimurium is facilitated by
the aquaglyceroporin, GlpF. A homologous protein in serovar Typhimurium, PduF,
facilitates the entry of 1,2-propanediol (Ppd) and is part of the Ppd metabolic
pathway. MGS catalyzes the elimination of phosphate from DHAP, forming an enzyme
bound enediol(ate) intermediate that is released from the enzyme, followed by
release of inorganic phosphate. The enzyme is highly specific for DHAP. Multiple
MG detoxification pathways are found in both E. coli and serovar Typhimurium, but
the dominant pathway is the GSH-dependent glyoxalase III system. The KefB and
KefC systems have evolved to provide protection during detoxification of
electrophiles. KefB and KefC are GSH-gated K+ efflux systems that are activated
by the formation and binding of glutathione adducts that are generated during
detoxification.
PMID- 26443507
TI - Catabolism of Amino Acids and Related Compounds.
AB - This review considers the pathways for the degradation of amino acids and a few
related compounds (agmatine, putrescine, ornithine, and aminobutyrate), along
with their functions and regulation. Nitrogen limitation and an acidic
environment are two physiological cues that regulate expression of several amino
acid catabolic genes. The review considers Escherichia coli, Salmonella enterica
serovar Typhimurium, and Klebsiella species. The latter is included because the
pathways in Klebsiella species have often been thoroughly characterized and also
because of interesting differences in pathway regulation. These organisms can
essentially degrade all the protein amino acids, except for the three branched
chain amino acids. E. coli, Salmonella enterica serovar Typhimurium, and
Klebsiella aerogenes can assimilate nitrogen from D- and L-alanine, arginine,
asparagine, aspartate, glutamate, glutamine, glycine, proline, and D- and L
serine. There are species differences in the utilization of agmatine, citrulline,
cysteine, histidine, the aromatic amino acids, and polyamines (putrescine and
spermidine). Regardless of the pathway of glutamate synthesis, nitrogen source
catabolism must generate ammonia for glutamine synthesis. Loss of glutamate
synthase (glutamineoxoglutarate amidotransferase, or GOGAT) prevents utilization
of many organic nitrogen sources. Mutations that create or increase a requirement
for ammonia also prevent utilization of most organic nitrogen sources.
PMID- 26443508
TI - Transfer RNA Modification.
AB - Transfer RNA (tRNA) from all organisms on this planet contains modified
nucleosides, which are derivatives of the four major nucleosides. tRNA from
Escherichia coli/Salmonella enterica contains 31 different modified nucleosides,
which are all, except for one (Queuosine[Q]), synthesized on an oligonucleotide
precursor, which through specific enzymes later matures into tRNA. The
corresponding structural genes for these enzymes are found in mono- and
polycistronic operons, the latter of which have a complex transcription and
translation pattern. The syntheses of some of them (e.g.,several methylated
derivatives) are catalyzed by one enzyme, which is position and base specific,
but synthesis of some have a very complex biosynthetic pathway involving several
enzymes (e.g., 2-thiouridines, N6-threonyladenosine [t6A],and Q). Several of the
modified nucleosides are essential for viability (e.g.,lysidin, t6A, 1
methylguanosine), whereas deficiency in others induces severe growth defects.
However, some have no or only a small effect on growth at laboratory conditions.
Modified nucleosides that are present in the anticodon loop or stem have a
fundamental influence on the efficiency of charging the tRNA, reading cognate
codons, and preventing missense and frameshift errors. Those, which are present
in the body of the tRNA, have a primarily stabilizing effect on the tRNA. Thus,
the ubiquitouspresence of these modified nucleosides plays a pivotal role in the
function of the tRNA by their influence on the stability and activity of the
tRNA.
PMID- 26443509
TI - Two-Carbon Compounds and Fatty Acids as Carbon Sources.
AB - This review concerns the uptake and degradation of those molecules that are
wholly or largely converted to acetyl-coenzyme A (CoA) in the first stage of
metabolism in Escherichia coli and Salmonella enterica. These include acetate,
acetoacetate, butyrate and longer fatty acids in wild type cells plus ethanol and
some longer alcohols in certain mutant strains. Entering metabolism as acetyl-CoA
has two important general consequences. First, generation of energy from acetyl
CoA requires operation of both the citric acid cycle and the respiratory chain to
oxidize the NADH produced. Hence, acetyl-CoA serves as an energy source only
during aerobic growth or during anaerobic respiration with such alternative
electron acceptors as nitrate or trimethylamine oxide. In the absence of a
suitable oxidant, acetyl-CoA is converted to a mixture of acetic acid and ethanol
by the pathways of anaerobic fermentation. Catabolism of acetyl-CoA via the
citric acid cycle releases both carbon atoms of the acetyl moiety as carbon
dioxide and growth on these substrates as sole carbon source therefore requires
the operation of the glyoxylate bypass to generate cell material. The pair of
related two-carbon compounds, glycolate and glyoxylate are also discussed.
However, despite having two carbons, these are metabolized via malate and
glycerate, not via acetyl-CoA. In addition, mutants of E. coli capable of growth
on ethylene glycol metabolize it via the glycolate pathway, rather than via
acetyl- CoA. Propionate metabolism is also discussed because in many respects its
pathway is analogous to that of acetate. The transcriptional regulation of these
pathways is discussed in detail.
PMID- 26443510
TI - Adhesins of Enterotoxigenic Escherichia coli Strains That Infect Animals.
AB - The first described adhesive antigen of Escherichia coli strains isolated from
animals was the K88 antigen, expressed by strains from diarrheic pigs. The K88
antigen was visible by electron microscopy as a surface-exposed filament that was
thin and flexible and had hemagglutinating properties. Many different fimbriae
have been identified in animal enterotoxigenic E. coli (ETEC) and have been
discussed in this article. The role of these fimbriae in the pathogenesis of ETEC
has been best studied with K88, K99, 987P, and F41. Each fimbrial type carries at
least one adhesive moiety that is specific for a certain host receptor,
determining host species, age, and tissue specificities. ETEC are the most
frequently diagnosed pathogens among neonatal and post-weaning piglets that die
of diarrhea. Immune electron microscopy of animal ETEC fimbriae usually shows
that the minor subunits are located at the fimbrial tips and at discrete sites
along the fimbrial threads. Since fimbriae most frequently act like lectins by
binding to the carbohydrate moieties of glycoproteins or glycolipids, fimbrial
receptors have frequently been studied with red blood cells of various animal
species. Identification and characterization of the binding moieties of ETEC
fimbrial adhesins should be useful for the design of new prophylactic or
therapeutic strategies. Some studies describing potential receptor or adhesin
analogues that interfere with fimbria-mediated colonization have been described
in the article.
PMID- 26443511
TI - Outer Membrane Vesicles.
AB - Outer membrane vesicles (blebs) are produced by Escherichia coli, Salmonella, and
all other gram-negative bacteria both in vitro and in vivo. Most of the research
in the field has focused on the properties of vesicles derived from pathogenic
bacteria and their interactions with eukaryotic cells. These data indicate that
vesicles are able to contribute to pathogenesis. Thus, it appears that pathogenic
gram-negative bacteria have co-opted vesicles for the dissemination of virulence
determinants. However, the role of vesicle production by nonpathogenic bacteria
is less obvious. This section reviews the data demonstrating the mechanistic and
physiological basis of outer membrane vesicle production by bacteria.
Vesiculation can be seen as a mechanism for cells to react to conditions in the
surrounding environment by carrying away unnecessary components and allowing
rapid modification of the outer membrane composition. In addition, vesicles can
transmit biological activities distant from the originating cell. Vesicles could
act to bind and deplete host immune factors at the site of infection that would
otherwise attack the bacteria. Vesicles in the area surrounding the cell may also
provide the cell protection inside a human or animal host. The concept of
vesicles as virulence factors has received considerable attention, and they are
likely to play a significant role in the pathogenesis of gram-negative bacteria.
By analysis of their composition, mechanism of formation, regulation, and
physiological function, progress is being made in understanding the ubiquitous
nature of outer membrane vesicles produced by gram-negative bacteria.
PMID- 26443512
TI - Adhesins of Diffusely Adherent and Enteroaggregative Escherichia coli.
AB - Epidemiological studies have implicated enteroaggregative Escherichia coli (EAEC)
strains in acute and persistent diarrhea in children, in food-borne diarrhea
outbreaks, and in traveler's diarrhea, and this group is recognized as an
emerging pathotype of enteric disease. Diffusely adherent E. coli (DAEC) have
been implicated as a cause of diarrhea, especially in children more than 2 years
old, in both developing and developed countries. Although EAEC and DAEC strains
appear to have different molecular equipment for attachment to host cell
surfaces, identification and characterization of the gene clusters encoding
adherence evidenced close relatedness between those determinants most frequently
detected in isolates belonging to these two pathotypes of diarrheagenic E. coli.
DAEC strains are a heterogeneous group of E. coli isolates, many of which express
the related so-called Dr adhesins. The single designation is based on the
identification of one similar cellular receptor for all these proteins. Although
structurally different, they all recognize the Dr human blood group antigen on
the decay-accelerating factor (DAF or CD55). These adhesins are encoded by a
family of closely related operons, the first characterized and sequenced being
the afa operon. Consequently, it has been suggested that this group of DAEC
strains producing such adhesins be named the Afa/Dr DAEC family. Three distinct
but closely related gene clusters coding for phenotypically and morphologically
distinct aggregative adherence fimbriae (AAF) have been characterized. In each
case, electron microscopy revealed that bacterial surfaces were surrounded by
long, relatively flexible fimbrial structures.
PMID- 26443513
TI - Nitric Oxide in Salmonella and Escherichia coli Infections.
AB - This review discusses the role that nitric oxide (NO) and its congeners play on
various stages in the pathophysiology of Escherichia coli and Salmonella
infections, with special emphasis on the regulatory pathways that lead to high NO
synthesis, the role of reactive nitrogen species (RNS) in host resistance, and
the bacterial molecular targets and defense mechanisms that protect enteric
bacteria against the nitrosative stress encountered in diverse host anatomical
sites. In general, NO can react directly with prosthetic groups containing
transition metal centers, with other radicals, or with sulfhydryl groups in the
presence of an electron acceptor. Binding to iron complexes is probably the best
characterized direct reaction of NO in biological systems. The targets of RNS are
numerous. RNS can facilitate oxidative modifications including lipid
peroxidation, hydroxylation, and DNA base and protein oxidation. In addition, RNS
can inflict nitrosative stress through the nitrosation of amines and sulfhydryls.
Numerous vital bacterial molecules can be targeted by NO. It is therefore not
surprising that enteropathogenic bacteria are armed with a number of sensors to
coordinate the protective response to nitrosative stress, along with an
assortment of antinitrosative defenses that detoxify, repair, or avoid the
deleterious effects of RNS encountered within the host. NO and NO-derived RNS
play important roles in innate immunity to Salmonella and E. coli. Enzymatic NO
production by NO synthases can be enhanced by microbial and other inflammatory
stimuli and it exerts direct antimicrobial actions as well as immunomodulatory
and vasoregulatory effects.
PMID- 26443514
TI - Shiga Toxins: Potent Poisons, Pathogenicity Determinants, and Pharmacological
Agents.
AB - The Shiga toxins (Stxs), also known as Vero toxins and previously called Shiga
like toxins, are a family of potent protein synthesis inhibitors made by Shigella
dysenteriae type 1 and some serogroups of Escherichia coli that cause bloody
diarrhea in humans. Stxs act as virulence factors for both S. dysenteriae and E.
coli and contribute to the disease process initiated by those organisms both
directly and indirectly. A handful of methods exist for toxin purification, and
the toxins can now even be purchased commercially. However, the Stxs are now
classified as select agents, and specific rules govern the distribution of both
the toxin and clones of the toxin. Toxin delivery into the host in S. dysenteriae
type 1 is most likely aided by the invasiveness of that organism. Although the
Stxs are made and produced by bacteria, they do not appear to act against either
their host organism or other bacteria under normal circumstances, most likely
because the A subunit is secreted from the cytoplasm as soon as it is synthesized
and because the holotoxin cannot enter intact bacterial cells. The effectiveness
of antibiotic therapy in patients infected with Stx-producing E. coli (STEC) such
as O157:H7 as well as the potential risks of such treatment are areas of
controversy. Several studies indicate that the course of the diarrhea stage of
the disease is unaltered by antibiotic treatment. Several groups anticipate that
a therapy that targets the Stxs is an important component of trying to alleviate
disease caused by Stx-producing bacteria.
PMID- 26443515
TI - Adhesins of Enterohemorrhagic Escherichia coli.
AB - Enterohemorrhagic Escherichia coli (EHEC) was first recognized as a cause of
human disease in 1983 and is associated with diarrhea and hemorrhagic colitis,
which may be complicated by life-threatening renal and neurological sequelae.
EHEC are defined by their ability to produce one or more Shiga-like toxins (Stx),
which mediate the systemic complications of EHEC infections, and to induce
characteristic attaching and effacing lesions on intestinal epithelia, a
phenotype that depends on the locus of enterocyte effacement. Acquisition of Stx
encoding bacteriophages by enteropathogenic E. coli is believed to have
contributed to the evolution of EHEC, and consequently some virulence factors are
conserved in both pathotypes. A key requirement for E. coli to colonize the
intestines and produce disease is the ability to adhere to epithelial cells
lining the gastrointestinal tract. Here, we review knowledge of the adhesins
produced by EHEC and other Stx-producing E. coli, with emphasis on genetic,
structural, and mechanistic aspects and their contribution to pathogenesis.
PMID- 26443516
TI - Hexose/Pentose and Hexitol/Pentitol Metabolism.
AB - Escherichia coli and Salmonella enterica serovar Typhimurium exhibit a remarkable
versatility in the usage of different sugars as the sole source of carbon and
energy, reflecting their ability to make use of the digested meals of mammalia
and of the ample offerings in the wild. Degradation of sugars starts with their
energy-dependent uptake through the cytoplasmic membrane and is carried on
further by specific enzymes in the cytoplasm, destined finally for degradation in
central metabolic pathways. As variant as the different sugars are, the
biochemical strategies to act on them are few. They include phosphorylation, keto
enol isomerization, oxido/reductions, and aldol cleavage. The catabolic
repertoire for using carbohydrate sources is largely the same in E. coli and in
serovar Typhimurium. Nonetheless, significant differences are found, even among
the strains and substrains of each species. We have grouped the sugars to be
discussed according to their first step in metabolism, which is their active
transport, and follow their path to glycolysis, catalyzed by the sugar-specific
enzymes. We will first discuss the phosphotransferase system (PTS) sugars, then
the sugars transported by ATP-binding cassette (ABC) transporters, followed by
those that are taken up via proton motive force (PMF)-dependent transporters. We
have focused on the catabolism and pathway regulation of hexose and pentose
monosaccharides as well as the corresponding sugar alcohols but have also
included disaccharides and simple glycosides while excluding polysaccharide
catabolism, except for maltodextrins.
PMID- 26443517
TI - Autotransporter Proteins.
AB - This review focuses on the function of the Escherichia coli and Salmonella
autotransporters for which a considerable amount of literature is available.
Members of the serine protease autotransporters of the Enterobacteriaceae
(SPATEs) family are proteins from E. coli and Shigella spp., which, like the
Neisseria and Haemophilus influenzae IgA1 proteases and Hap, possess a consensus
serine protease motif. The largest subfamily of autotransporters is defined by
the AidA conserved domain COG3468 and consists of members from a diverse range of
animal and plant pathogens including E. coli, S. enterica, Yersinia pestis. This
subfamily, which is composed of more than 55 proteins, possesses some of the best
characterized autotransporter proteins including the S. flexneri mediator of
motility IcsA, the major phase-variable E. coli outer membrane protein antigen 43
(Ag43) and the diffuse adhering E. coli (DAEC) adhesin AIDA-I, from which this
subfamily derives its name. Another member of the AIDA-I family, and one of the
most studied autotransporter proteins, is IcsA. The autotransporter pathway is
emerging as the most common mechanism of protein translocation across the gram
negative outer membrane.
PMID- 26443518
TI - Colonization of Abiotic Surfaces.
AB - E. coli is a relevant model organism for the study of the molecular mechanisms
underlying surface colonization. This process requires two essential steps:
adhesion to a surface, followed by cell-cell adhesion counteracting the shear
forces of the environment, with both steps contributing to the formation of a
biofilm. This review provides an overview of the current knowledge of the genetic
analyses aiming at identifying factors involved in both of these two highly
related biological processes, with a particular emphasis on studies performed in
Escherichia coli K-12. Bacterial adhesion to abiotic surfaces is likely to be
highly dependent on the physicochemical and electrostatic interactions between
the bacterial envelope and the substrate, which is itself often conditioned by
the fluids to which it is exposed. Genetic analyses have revealed the diversity
of genetic factors in E. coli that participate in colonization and biofilm
formation on abiotic surfaces. The study of surface colonization and biofilm
formation represents a rapidly expanding field of investigation. The use of E.
coli K-12 to investigate the genetic basis of bacterial interactions with
surfaces has led to the identification of a large repertoire of adhesins whose
expression is subject to a complex interplay between regulatory networks.
Understanding how E. coli K-12 behaves in complex biofilm communities will
certainly contribute to an understanding of how natural commensal and pathogenic
E. coli isolates develop.
PMID- 26443519
TI - Imaging Techniques for the Study of Escherichia coli and Salmonella Infections.
AB - Infectious diseases are among the leading causes of mortality worldwide, and
numerous bacterial species are included in the vast array of causative agents.
This review describes microscopy-based techniques that can be used to study
interactions between bacteria and infected host cells, bacterial gene expression
in the infected animal, and bacteria-induced cell signaling in eukaryotic cells.
As infectious model systems, urinary tract infections caused by uropathogenic
Escherichia coli (UPEC) and a mouse model of typhoid fever caused by Salmonella
enterica serovar Typhimurium are used. To study the interaction mechanism between
bacteria and eukaryotic cells, one commonly uses cell lines, primary cells, and
animal models. Within the host, bacteria can be located in various organs where
they are exposed to different cell types, ranging from epithelial cells at the
mucosal linings to phagocytic white blood cells. In each site, bacteria are
exposed to specific sets of innate immune defense mechanisms, and to survive
these threats, bacteria must rapidly adapt their gene expression profile to
maximize their chance of survival in any situation. The rapid development of
fluorescent reporter proteins and advances in microscopy-based techniques have
provided new and promising approaches not only to locate bacteria in tissues, but
also to analyze expression of virulence factors in individual bacteria and host
cells during the progression of disease. These techniques enable, for the first
time, studies of the complex microenvironments within infected organs and will
reveal the alterations of bacterial physiology that occur during bacterial growth
within a host.
PMID- 26443520
TI - Tricarboxylic Acid Cycle and Glyoxylate Bypass.
AB - The tricarboxylic acid (TCA) cycle plays two essential roles in metabolism.
First, under aerobic conditions the cycle is responsible for the total oxidation
of acetyl-CoA that is derived mainly from the pyruvate produced by glycolysis.
Second, TCA cycle intermediates are required in the biosynthesis of several amino
acids. Although the TCA cycle has long been considered a "housekeeping" pathway
in Escherichia coli and Salmonella enterica, the pathway is highly regulated at
the transcriptional level. Much of this control is exerted in response to
respiratory conditions. The TCA cycle gene-protein relationship and mutant
phenotypes have been well studied, although a few loose ends remain. The
realization that a "shadow" TCA cycle exists that proceeds through methylcitrate
has cleared up prior ambiguities. The glyoxylate bypass has long been known to be
essential for growth on carbon sources such as acetate or fatty acids because
this pathway allowsnet conversion of acetyl-CoA to metabolic intermediates.
Strains lacking this pathway fail to grow on these carbon sources, since acetate
carbon entering the TCA cycle is quantitatively lost as CO2 resulting in the lack
of a means to replenish the dicarboxylic acids consumed in amino acid
biosynthesis. The TCA cycle gene-protein relationship and mutant phenotypes have
been well studied, although the identity of the small molecule ligand that
modulates transcriptional control of the glyoxylate cycle genes by binding to the
IclR repressor remains unknown. The activity of the cycle is also exerted at the
enzyme level by the reversible phosphorylation of the TCA cycle enzyme isocitrate
dehydrogenase catalyzed by a specific kinase/phosphatase to allow isocitratelyase
to compete for isocitrate and cleave this intermediate to glyoxylate and
succinate.
PMID- 26443521
TI - Salmonella Epidemiology and Pathogenesis in Food-Producing Animals.
AB - This review reviews the pathogenesis of different phases of Salmonella
infections. The nature of Salmonella infections in several domesticated animal
species is described to highlight differences in the epidemiology and
pathogenesis of salmonellosis in different hosts. The biology of Salmonella
serovar host specificity is discussed in the context of our current understanding
of the molecular basis of pathogenesis and the potential impact of different
virulence determinants on Salmonella natural history. The ability to colonize the
intestine, as evidenced by the shedding of relatively large numbers of bacteria
in the feces over a long period, is shared unequally by Salmonella serovars.
Studies probing the molecular basis of Salmonella intestinal colonization have
been carried out by screening random transposon mutant banks of serovar
Typhimurium in a range of avian and mammalian species. It is becoming
increasingly clear that Salmonella pathogenicity island 2 (SPI2) is a major
virulence factor during infection of food-producing animals, including cattle and
poultry. The prevalence of Salmonella serovars in domestic fowl varies in
different countries and with time. Although chickens are the natural hosts of
serovars Gallinarum and Pullorum, natural outbreaks caused by these serovars in
turkeys, guinea fowl, and other avian species have been described. There are two
possible explanations to account for the apparent host specificity of certain
Salmonella serovars. Environmental factors may increase exposure of particular
animal species to certain serovars. Alternatively, there are genetic differences
between these serovars, which allow them to survive and/or grow in specific
niches only found within ruminants or pigs.
PMID- 26443522
TI - Intracellular Voyeurism: Examining the Modulation of Host Cell Activities
bySalmonella enterica Serovar Typhimurium.
AB - Salmonella spp. can infect host cells by gaining entry through phagocytosis or by
inducing host cell membrane ruffling that facilitates bacterial uptake. With its
wide host range, Salmonella enterica serovar Typhimurium has proven to be an
important model organism for studying intracellular bacterial pathogenesis. Upon
entry into host cells, serovar Typhimurium typically resides within a membrane
bound compartment termed the Salmonella-containing vacuole (SCV). From the SCV,
serovar Typhimurium can inject several effector proteins that subvert many normal
host cell systems, including endocytic trafficking, cytoskeletal rearrangements,
lipid signaling and distribution, and innate and adaptive host defenses. The
study of these intracellular events has been made possible through the use of
various imaging techniques, ranging from classic methods of transmission electron
microscopy to advanced livecell fluorescence confocal microscopy. In addition,
DNA microarrays have now been used to provide a "snapshot" of global gene
expression in serovar Typhimurium residing within the infected host cell. This
review describes key aspects of Salmonella-induced subversion of host cell
activities, providing examples of imaging that have been used to elucidate these
events. Serovar Typhimurium engages specific host cell machinery from initial
contact with the host cell to replication within the SCV. This continuous
interaction with the host cell has likely contributed to the extensive arsenal
that serovar Typhimurium now possesses, including two type III secretion systems,
a range of ammunition in the form of TTSS effectors, and a complex genetic
regulatory network that coordinates the expression of hundreds of virulence
factors.
PMID- 26443523
TI - Changes in the transcriptome of bovine ovarian cortex during follicle activation
in vitro.
AB - The signals that regulate activation, a key transition in ovarian follicular
development, are still not well understood, especially in nonrodent species. To
gain insight into the regulation of this transition in cattle, we combined a
microarray approach with an in vitro system in which ovarian cortical pieces
cultured in control medium are enriched for primordial follicles, whereas pieces
cultured with insulin are enriched for primary follicles. Total RNA was extracted
from cultured cortical pieces, and then transcripts were identified and analyzed
using the Affymetrix Bovine Genome GeneChip array. Around 65% of the transcripts
in the bovine GeneChip were detected in cultured cortical pieces. Comparison
between pieces cultured with or without insulin generated 158 differentially
expressed transcripts. Compared with controls, 90 transcripts were upregulated
and 68 were downregulated by insulin. These transcripts are involved in many
biological processes and functions, but most are associated with cellular growth
or cell cycle/cell death. The transcript encoding ubiquitin-conjugating enzyme
E2C (UBE2C) was significantly upregulated during follicle activation, and
Ingenuity Pathways Analysis revealed that UBE2C can interact with the tumor
suppressor phosphatase and tensin homolog (PTEN). Both PTEN mRNA and protein were
lower in cortical pieces cultured with insulin than in controls. In addition,
FOXO3a, a downstream effector of PTEN signaling, underwent nuclear-cytoplasmic
shuttling during primordial to primary follicle development in bovine fetal
ovaries, further suggesting the involvement of the PTEN pathway in follicle
activation in cattle. Genes and pathways identified in this study provide
interesting candidates for further investigation of mechanisms underlying
follicle activation.
PMID- 26443525
TI - Patched bimetallic surfaces are active catalysts for ammonia decomposition.
AB - Ammonia decomposition is often used as an archetypical reaction for predicting
new catalytic materials and understanding the very reason of why some reactions
are sensitive on material's structure. Core-shell or surface-segregated
bimetallic nanoparticles expose outstanding activity for many heterogeneously
catalysed reactions but the reasons remain elusive owing to the difficulties in
experimentally characterizing active sites. Here by performing multiscale
simulations in ammonia decomposition on various nickel loadings on platinum
(111), we show that the very high activity of core-shell structures requires
patches of the guest metal to create and sustain dual active sites: nickel
terraces catalyse N-H bond breaking and nickel edge sites drive atomic nitrogen
association. The structure sensitivity on these active catalysts depends
profoundly on reaction conditions due to kinetically competing relevant
elementary reaction steps. We expose a remarkable difference in active sites
between transient and steady-state studies and provide insights into optimal
material design.
PMID- 26443524
TI - Crosstalk between purinergic receptors and canonical signaling pathways in the
mouse salivary gland.
AB - Isolated clusters of mouse parotid acinar cells in combination with live cell
imaging were used to explore the crosstalk in molecular signaling between
purinergic, cholinergic and adrenergic pathways that integrate to control fluid
and protein secretion. This crosstalk was manifested by (1) beta-adrenergic
receptor activation and amplification of P2X4R evoked Ca(2+) signals, (2) beta
adrenergic-induced amplification of P2X7R-evoked Ca(2+) signals and (3)
muscarinic receptor induced activation of P2X7Rs via exocytotic activity. The
findings from our study reveal that purinoceptor-mediated Ca(2+) signaling is
modulated by crosstalk with canonical signaling pathways in parotid acinar cells.
Integration of these signals are likely important for dynamic control of saliva
secretion to match physiological demand in the parotid gland.
PMID- 26443526
TI - Whispering-gallery nanocavity plasmon-enhanced Raman spectroscopy.
AB - The synergy effect in nature could enable fantastic improvement of functional
properties and associated effects. The detection performance of surface-enhanced
Raman scattering (SERS) can be highly strengthened under the cooperation with
other factors. Here, greatly-enhanced SERS detection is realized based on rolled
up tubular nano-resonators decorated with silver nanoparticles. The synergy
effect between whispering-gallery-mode (WGM) and surface plasmon leads to an
extra enhancement at the order of 10(5) compared to non-resonant flat SERS
substrates, which can be well tuned by altering the diameter of micron- and
nanotubes and the excitation laser wavelengths. Such synchronous and coherent
coupling between plasmonics and photonics could lead to new principle and design
for various sub-wavelength optical devices, e.g. plasmonic waveguides and
hyperbolic metamaterials.
PMID- 26443527
TI - Prophylactic Laparoscopic Total Gastrectomy with Jejunal Pouch Reconstruction in
Patients Carrying a CDH1 Germline Mutation.
AB - BACKGROUND: For patients with an identified germline E-cadherin-1 (CDH1)
mutation, prophylactic gastrectomy is the treatment of choice to eliminate the
high risk of developing diffuse gastric cancer. Laparoscopic total gastrectomy
with jejunal pouch reconstruction is a novel approach that may be especially
suitable in these patients. METHODS: Patients with a germline CDH1 mutation who
underwent prophylactic laparoscopic total gastrectomy with jejunal pouch were
included in our prospective database. RESULTS: A total of 11 patients with a
median age of 40 (22-61) years were included. The average operative time was 4:26
+/- 0:49 h and the average blood loss was 219 +/- 155 ml. Median length of
hospital stay was 10 (7-27) days. In two patients, an esophagojejunal anastomotic
leakage occurred (grade 4). The leakages were seen in patient numbers 2 and 3,
which may be a result of a learning curve. The latter eight patients did not
develop anastomotic leakage. Pulmonary complications occurred in one patient with
atelectasis and in one patient with pneumonia (grade 2). The 60-day mortality
rate was 0 %. Multiple foci of intramucosal diffuse gastric signet ring cell
carcinoma were found in the resection specimen of 9/11 (82 %) patients. All 11/11
(100 %) resections were microscopically radical. CONCLUSIONS: Prophylactic
laparoscopic total gastrectomy with jejunal pouch reconstruction in patients with
a CDH1 germline mutation is feasible and safe. In 82 % of patients, foci of
intramucosal diffuse gastric signet ring cell carcinoma in the resection specimen
were found.
PMID- 26443528
TI - The Neutrophil-to-Lymphocyte Ratio Predicts Malignant Potential in Intraductal
Papillary Mucinous Neoplasms.
AB - BACKGROUND: Accurately identifying malignant components in patients with
pancreatic intraductal papillary mucinous neoplasms (IPMN) remains challenging.
Preoperative neutrophil-to-lymphocyte ratio (NLR) is a marker of poor prognosis
in patients with several types of malignancy. This study assessed whether NLR was
predictive of intraductal papillary mucinous carcinoma (IPMC) in patients with
IPMN. METHOD: This study retrospectively assessed 76 patients who underwent
curative resection for IPMN from 1995 to 2015. The correlation between the
presence of malignant components and preoperative NLR was analyzed. RESULTS:
Preoperative NLR in IPMC was significantly higher in patients with in IPMC (2.51
+/- 0.84) than in patients with intraductal papillary mucinous adenoma (2.01 +/-
0.71, P = 0.0079) and healthy volunteers (1.37 +/- 0.33, P < 0.0001). NLR was
significantly reduced after curative tumor resection. The main duct type (P =
0.0231) and NLR >2.074 (P = 0.0329) were independent predictors of IPMC in all
patients. Combined criteria including international consensus guidelines, CA19-9
>37 IU/ml, and NLR >2.074 shows a high positive predictive value of 78 % and high
specificity of 96 %. CONCLUSIONS: Preoperative NLR is a useful supportive marker
to predict IPMC in patients with IPMN.
PMID- 26443529
TI - Is Abdominal Fat Distribution Measured by Axial CT Imaging an Indicator of
Complications and Mortality in Acute Pancreatitis?
AB - BACKGROUND: Obesity is an important risk-stratifying co-morbidity for many
pathological conditions. Controversy exists about its influence in outcomes after
acute pancreatitis (AP). This study assessed abdominal fat distribution
(subcutaneous, retroperitoneal and intra-abdominal) measured using computer
tomography (CT) images and related it to outcomes in patients with AP. METHODS:
The case notes of patients admitted with AP were identified from computerised
records from 2008 to the 2013. Image analysis software was used to assess the
individual abdominal fat distributions from CT images. RESULTS: A total of 79
patients were included. There was no relationship between fat distribution and
either severity of, or mortality from, AP. Fat distribution was not found to be
an independent risk factor on multivariate analysis. There was, however, a
positive correlation between retroperitoneal and intra-abdominal fat with APACHE
II scores, Ranson and Glasgow score and Multiple Organ Dysfunction score (MODS)
on various days following admission (r = 0.421, p = 0.0008; r = 0.469, p <
0.0001; r = 0.398, p = 0.007; r = 0.336, p = 0.011, respectively). On multiple
logistical regression analysis, the only variables associated with mortality were
Balthazar Severity Index, MODS and EWS with a p value of <0.0001, 0.0019 and
0.0481, respectively. CONCLUSIONS: Obese patients have worse predicted outcomes
as measured by the EWS, MODS and Ranson scores. Abdominal fat distribution,
however, was not shown to be directly related to AP severity or mortality. The
addition of fat parameters may be of use in prognostic CT severity index models,
but from this data, it does not appear to be an independent risk factor of
adverse outcome.
PMID- 26443531
TI - The 2015 Karl Meyer Lectureship Award and the Rosalind Kornfeld Award for
Lifetime Achievement in Glycobiology, from the Society for Glycobiology.
PMID- 26443532
TI - Remembering J. A. Cifonelli (1916-2005) An Early Leader in Glycosaminoglycan
Biochemistry.
PMID- 26443533
TI - Using political science to progress public health nutrition: a systematic review.
AB - OBJECTIVE: Poor dietary intake is the most important behavioural risk factor
affecting health globally. Despite this, there has been little investment in
public health nutrition policy actions. Policy process theories from the field of
political science can aid understanding why policy decisions have occurred and
identify how to influence ongoing or future initiatives. The present review aims
to examine public health nutrition policy literature and identify whether a
policy process theory has been used to analyse the process. DESIGN: Electronic
databases were searched systematically for studies examining policy making in
public health nutrition in high-income, democratic countries. SETTING:
International, national, state and local government jurisdictions within high
income, democratic countries. SUBJECTS: Individuals and organisations involved in
the nutrition policy-making process. RESULTS: Sixty-three studies met the
eligibility criteria, most were conducted in the USA and a majority focused on
obesity. The analysis demonstrates an accelerating trend in the number of
nutrition policy papers published annually and an increase in the diversity of
nutrition topics examined. The use of policy process theory was observed from
2003; however, it was utilised by only 14 % of the reviewed papers. CONCLUSIONS:
There is limited research into the nutrition policy process in high-income
countries. While there has been a small increase in the use of policy process
theory from 2003, an opportunity to expand its use is evident. We suggest that
nutrition policy making would benefit from a pragmatic approach that ensures
those trying to influence or understand the policy-making process are equipped
with basic knowledge around these theories.
PMID- 26443534
TI - Pseudoxanthomonas humi sp. nov., a bacterium isolated from rhizospheric soil of
Fraxinus chinensis in Gyeonggi Province, South Korea.
AB - A novel bacterial strain THG-MM13(T) was isolated from rhizospheric soil sample
and was characterized by using a polyphasic approach. Cells were Gram-reaction
negative, non-motile and rod-shaped. The strain was aerobic, catalase and oxidase
positive, and optimum growth temperature and pH were 28 degrees C and 7.0,
respectively. On the basis of 16S rRNA gene sequence analysis, strain THG-MM13(T)
(KM598260) belongs to the genus Pseudoxanthomonas and is most closely related to
Pseudoxanthomonas wuyuanensis KCTC 23877(T) (97.4 %) (JN247803), followed by
Pseudoxanthomonas koreensis KCTC 12208(T) (96.7 %) (AY550263) and
Pseudoxanthomonas yeongjuensis KACC 11580(T) (96.7 %) (DQ438977). The DNA G + C
content was 63.7 mol%, and the predominant respiratory quinone was ubiquinone-8.
The major polar lipids were diphosphatidylglycerol and phosphatidylethanolamine.
The major fatty acids were iso-C15:0 (31.3 %) and iso-C16:0 (19.3 %). The DNA-DNA
relatedness value between strain THG-MM13(T) and P. wuyuanensis KCTC 23877(T) was
below 50 %. The DNA-DNA hybridization result and results of the genotypic
analysis in combination with chemotaxonomic and physiological data demonstrated
that strain THG-MM13(T) represented a novel species within the genus
Pseudoxanthomonas, for which the name Pseudoxanthomonas humi is proposed. The
type strain is THG-MM13(T) (=KACC 18280(T) = CCTCC AB 2015122(T)).
PMID- 26443535
TI - Posterior Humeral Avulsion of the Glenohumeral Ligament and Associated Injuries:
Assessment Using Magnetic Resonance Imaging.
AB - BACKGROUND: Lesions associated with posterior humeral avulsion of the
glenohumeral ligament (HAGL) can lead to persistent symptoms related to posterior
shoulder instability and can be commonly missed or delayed in diagnosis. PURPOSE:
To identify and characterize the MRI findings in patients with a posterior HAGL
lesion. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This
retrospective case series included 27 patients (28 shoulders) identified by
search through the senior authors' databases, with cross-reference to their
institutional radiologic communication system for MRI review. Baseline patient
demographic data were collected, including age and sex. All posterior HAGL
lesions were identified on MRI and characterized as partial, complete, or
floating lesions. All acute glenohumeral pathologic changes concurrent with the
posterior HAGL were documented. Chondrolabral retroversion of the injured
shoulder was measured on axial MRI. RESULTS: The average age of the identified
cohort was 33.6 years (range, 15-81 years), and 23 patients were male (86%).
Posterior HAGL injuries were found to be complete tears (71%), partial tears
(25%), and floating lesions (4%); concomitant bony HAGL avulsion was found in 7%
of injuries. Additional traumatic glenohumeral disorders occurred in 93% of
cases. The most common concurrent injuries were reverse Hill-Sachs lesions (36%),
anterior Bankart lesions (29%), and posterosuperior rotator cuff tears (25%).
Notably, concomitant anterior labral or capsular injury was found in 50% of
patients, signifying bidirectional disruption of the capsule. In addition,
increased chondrolabral version was found in this cohort (10.2 degrees +/- 3.7
degrees retroversion). CONCLUSION: This study depicts the high association of
combined injury with posterior HAGL lesions and increased chondrolabral
retroversion. Findings on MRI related to a posterior HAGL injury could
potentially be masked by additional injury and may occur with mechanisms that
also lead to anterior glenohumeral disorders.
PMID- 26443536
TI - Radiographic Identification of the Deltoid Ligament Complex of the Medial Ankle.
AB - BACKGROUND: An injury to the deltoid ligament complex of the ankle can require
surgical intervention in cases of chronic instability. There is an absence of
data describing medial ankle ligament anatomy on standard radiographic views.
PURPOSE: To quantitatively describe the anatomic origins and insertions of the
individual ligamentous bands of the superficial and deep deltoid on standard
lateral and mortise radiographic views with reference to osseous landmarks and
anatomic axes. STUDY DESIGN: Descriptive laboratory study. METHODS: Twelve
nonpaired, fresh-frozen cadaveric foot and ankle specimens were utilized.
Specimens were dissected free of all overlying soft tissue to identify individual
ligamentous bands of the superficial and deep deltoid ligaments and to isolate
their distinct origins and insertions. Footprint centers were identified on
standard lateral and mortise radiographs by 2-mm stainless steel spheres embedded
at the level of the cortical bone. Distances to osseous landmarks were measured
independently by 2 blinded reviewers to calculate mean distances and evaluate
reliability and repeatability measures using intraclass correlation coefficients.
RESULTS: Varying subsets of the 4 superficial deltoid bands including the
tibionavicular (12/12), tibiospring (12/12), tibiocalcaneal (9/12), and
superficial posterior tibiotalar (9/12) ligaments were found across specimens. On
the lateral view, the tibionavicular ligament was the most anterior and attached
7.6 +/- 1.9 mm superior and anterior to the inferior tip of the medial malleolus.
The tibiospring ligament attached 12.1 +/- 2.2 mm superior and anterior to the
inferior tip of the medial malleolus and attached to the spring ligament, which
coursed from its origin 12.3 +/- 1.6 mm anterior and slightly inferior to the
posterior point of the sustentaculum tali to its insertion on the navicular
tuberosity. The tibiocalcaneal ligament and superficial posterior tibiotalar
ligament were found posteriorly in the majority of specimens. Two constituents of
the deep deltoid, including the deep anterior tibiotalar (11/12) and deep
posterior tibiotalar (12/12) ligaments, were found in the majority of specimens.
The deep posterior was larger and coursed from the tibia, 8.1 +/- 2.2 mm
posterior and superior to the inferior tip of the medial malleolus, to its
attachment on the talus, 15.5 +/- 2.4 mm superior and anterior to the posterior
inferior point of the talus on the lateral view. CONCLUSION: Quantitative
radiographic relationships describing the anatomic origins and insertions of the
individual superficial and deep deltoid constituents were defined with excellent
reliability and reproducibility. CLINICAL RELEVANCE: Radiographic parameters will
augment current anatomic data by assisting with preoperative planning,
intraoperative guidance, and postoperative assessment. These radiographic
guidelines will facilitate the development of novel anatomic reconstructions and
allow surgeons to plan the locations of reconstruction tunnels.
PMID- 26443538
TI - Ambulance Dispatches From Unaffected Areas After the Great East Japan Earthquake:
Impact on Emergency Care in the Unaffected Areas.
AB - OBJECTIVE: Although dispatching ambulance crews from unaffected areas to a
disaster zone is inevitable when a major disaster occurs, the effect on emergency
care in the unaffected areas has not been studied. We evaluated whether
dispatching ambulance crews from unaffected prefectures to those damaged by the
Great East Japan Earthquake was associated with reduced resuscitation outcomes in
out-of-hospital cardiac arrest (OHCA) cases in the unaffected areas. METHODS: We
used the Box-Jenkins transfer function model to assess the relationship between
ambulance crew dispatches and return of spontaneous circulation (ROSC) before
hospital arrival or 1-month survival after the cardiac event. RESULTS: In a model
whose output was the rate of ROSC before hospital arrival, dispatching 1000
ambulance crews was associated with a 0.474% decrease in the rate of ROSC after
the dispatch in the prefectures (p=0.023). In a model whose output was the rate
of 1-month survival, dispatching 1000 ambulance crews was associated with a
0.502% decrease in the rate of 1-month survival after the dispatch in the
prefectures (p=0.011). CONCLUSIONS: The dispatch of ambulances from unaffected
prefectures to earthquake-stricken areas was associated with a subsequent
decrease in the ROSC and 1-month survival rates in OHCA cases in the unaffected
prefectures.
PMID- 26443539
TI - Overexpression of Rab5a promotes hepatocellular carcinoma cell proliferation and
invasion via FAK signaling pathway.
AB - Rab5a was reported to be overexpressed in human malignancy and associated with
the malignant phenotype. To data, its expression pattern and biological function
in hepatocellular carcinoma (HCC) have not been studied. We analyzed Rab5a
protein expression in 98 cases of HCC tissues and four HCC cell lines. We found
that Rab5a expression was upregulated in HCC tissues and cell lines. Rab5a
overexpression correlated with TNM stage and nodal metastasis (p < 0.05). To
confirm the biological function of Rab5a in HCC cell lines, Rab5a siRNA was
employed in SK-Hep-1 cell line and plasmid transfection was performed in Huh7
cell line. CCK-8 assay showed that Rab5a depletion blocked cell growth rate while
Rab5a overexpression facilitated proliferation. Transwell and migration assay
showed that Rab5a positively regulated cell invasion and migration. To explore
the molecular mechanism underlying the biological effects of Rab5a, we checked
several signaling pathways and found that Rab5a overexpression upregulated cyclin
D1, cyclin E expression, FAK (Tyr397), and AKT (Ser473) phosphorylation. Blockage
of FAK using inhibitor PF573228 abolished the role of Rab5a on cyclin D1. In
conclusion, Rab5a is overexpressed in human HCC and contributes to cancer cell
proliferation and invasion through regulation of FAK and AKT signaling.
PMID- 26443540
TI - Overexpression of acylglycerol kinase is associated with poorer prognosis and
lymph node metastasis in nasopharyngeal carcinoma.
AB - Acylglycerol kinase (AGK) has been reported to promote a malignant phenotype and
enhance the development of cancer stem cells. However, the clinical value of AGK
in cancer remains unclear. This study aimed to investigate the expression and
clinicopathological significance of AGK in nasopharyngeal carcinoma (NPC). AGK
was significantly upregulated in NPC cell lines and clinical specimens as
indicated by real-time PCR and Western blotting. Among the AGK-positive cases,
52/114 (45.6 %) of the archived human NPC specimens expressed high levels of AGK.
High expression of AGK was associated with significantly shorter overall and
disease-free survival (P < 0.001 and P = 0.002; log-rank test) and was an
independent prognostic factor for overall survival (P = 0.041; multivariate Cox
analysis). High AGK expression was associated with lymph node metastasis (P <
0.001; chi-squared test) and was an independent predicted factor for lymph node
metastasis in NPC (P = 0.032; multivariate logistic analysis). AGK is
overexpressed and associated with disease progression and lymph node metastasis
in NPC. AGK has potential as a novel prognostic factor for overall survival in
NPC.
PMID- 26443541
TI - Engaging youth in communities: a framework for promoting adolescent and community
health.
AB - Health researchers and practitioners increasingly recognise the important role
communities play in shaping individual health. Health researchers recognise the
role of community factors as causes or determinants of health problems; use
community-based methods for understanding complex health issues; and design
community-level health solutions. In this commentary, we propose a fourth way to
think about the role of communities in individual health by arguing that the
community engagement process itself has implications for individual health and
strong communities. This topic is especially important during adolescence, a
developmental window of opportunity during which individuals need meaningful
opportunities to contribute to the world around them.
PMID- 26443542
TI - Surgical repair of complete atrioventricular defect (Nunn technique).
AB - Two procedures have been traditionally used for the surgical repair of complete
atrioventricular canal. The single-patch technique includes the division of valve
leaflets, and the use of one patch to close the ventricular and the atrial septal
defects, whereas the double-patch technique uses two separate patches, without
the division of the bridging leaflets. Between 1997 and 2007, another technique
emerged, the modified single-patch technique, or the 'Australian' technique,
whereby the ventricular septal defect (VSD) is closed by the direct apposition of
the bridging leaflets against the crest of the defect. Because of the absence of
the ventricular septal patch, concerns have been raised about the possible left
ventricular outflow tract obstruction (LVOTO), or atrioventricular valve (AVV)
distortion, especially in case of a deep VSD, or if the defect extends
superiorly. The results of the modified single-patch technique in terms of
mortality, immediate and long-term AVV function and LVOTO have been similar to
the standard techniques in most reports. This article will describe in detail the
operative technique and review the relevant literature.
PMID- 26443543
TI - ERK5/HDAC5-mediated, resveratrol-, and pterostilbene-induced expression of MnSOD
in human endothelial cells.
AB - SCOPE: Mitochondrial oxidative stress is closely correlated with numerous
cardiovascular diseases. Manganese superoxide dismutase (MnSOD) is an important
antioxidant enzyme in mitochondria. Although polyphenols can induce the
expression of MnSOD, their corresponding mechanisms remains unclear. In this
study, we tested the hypothesis that resveratrol and pterostilbene can activate
the expression of MnSOD through an AMPK-ERK5/HDAC5-KLF2 pathway. METHODS AND
RESULTS: Our results revealed that two stilbenes reduced mitochondrial superoxide
free radicals, and endothelial cell senescence, and increased the mRNA expression
of several genes related to mitochondrial function, including MnSOD. Moreover,
two stilbenes upregulated the activation of human MnSOD promoter luciferase
reporter gene and protein level in human umbilical vein endothelial cells.
Similarly, two stilbenes also stimulated LKB1, AMPKalpha, extracellular-signal
related kinase 5 (ERK5) phosphorylation, and histone acetylase 5 (HDAC5) and
Kruppel-like factor 2 (KLF2) expression. The knockdown of AMP-activated protein
kinase (AMPK), ERK5, and HDAC5 by using short-hairpin RNA blocked pterostilbene
induced phosphorylation of their downstream signaling proteins and the expression
of KLF2. Furthermore, using a chromatin immunoprecipitation-PCR detection method,
we found that resveratrol and pterostilbene promoted KLF2 binding to CACCC sites
of the human MnSOD promoter. CONCLUSION: Resveratrol and pterostilbene can
activate MnSOD expression through ERK5/HDAC5 pathway, thus alleviating
mitochondrial oxidative stress in endothelial cells that relates to
cardiovascular disease.
PMID- 26443544
TI - A STUDY ON THE UNCERTAINTY FOR THE ROUTINE DOSIMETRY SERVICE AT THE LEBANESE
ATOMIC ENERGY COMMISSION USING HARSHAW 8814 DOSEMETERS.
AB - The personal dosimetry service at the Lebanese Atomic Energy Commission uses
Harshaw 8814 cards with LiF:Mg,Ti detectors. The dosemeters are read in a Harshaw
6600 TLD reader. In the process of accreditation for the ISO 17025 standard((1)),
different influence factors are investigated and the uncertainty has been
determined. The Individual Monitoring Service Laboratory-LAEC reads the
dosemeters once it receives them from the customer, and new cards are immediately
given for the next wearing period. The wearing period is 2 months. The dosemeter
results are reported to the customers without background subtraction. Both Hp(10)
and Hp(0.07) are reported. For this paper, only the uncertainty on Hp(10) will be
focussed. The following factors are taken into account for the uncertainty:
calibration factor, dosemeter homogeneity and repeatability, energy and angular
dependence, non-linearity, temperature dependence, etc. Also the detection limit
was determined. One of the important factors is the correction for fading. This
fading correction depends on the procedure used such as storage temperatures, the
time-temperature profile of the read-out, pre-heat and annealing conditions. Pre-
and post-irradiation fading curves were measured for a storage period up to 182 d
at room temperature (15-25 degrees C). The resulting final combined standard
uncertainty on the reported doses is of the order of 24 % for doses of ~1 mSv.
PMID- 26443545
TI - EVOLUTION OF THE IEC AND EN STANDARDS FOR INDIVIDUAL MONITORING OF IONISING
RADIATION.
AB - This article presents the evolution of the International Electrotechnical
Commission (IEC) and the European standards for individual monitoring of ionising
radiation issued, respectively, from the committees IEC/Sub Committee 45B and
European Committee for Electro-technical Standardization/Technical Committee 45B
'Radiation protection instrumentation'. Standards for passive individual photon
and beta dosimetry systems as well as those for active individual monitors are
discussed. A neutron ambient dose equivalent (rate) meter standard and a
technical report concerning the determination of uncertainty in measurement are
also covered.
PMID- 26443546
TI - COMPARISON OF DIFFERENT PADC MATERIALS AND ETCHING CONDITIONS FOR FAST NEUTRON
DOSIMETRY.
AB - Etched-track polyallyl diglycol carbonate (PADC) dosemeters have been in use at
the Paul Scherrer Institute since 1998 in neutron dosimetry for individual
monitoring. In the last years, the availability of PADC materials from different
manufacturers has grown, and different etching conditions were proposed, with the
intention to improve the quality and overall performance of PADC in individual
neutron monitoring. The goal of the present study was to compare the performance
of different PADC materials and to investigate the influence of different etching
conditions on sensitivity to fast neutrons and lower detection limit. The
comparison covers six different PADC materials and eight different etching
conditions.
PMID- 26443547
TI - MONTE CARLO SIMULATION OF THE BREMSSTRAHLUNG RADIATION FOR THE MEASUREMENT OF AN
INTERNAL CONTAMINATION WITH PURE-BETA EMITTERS IN VIVO.
AB - Rapid measurement techniques are required for a large-scale emergency monitoring
of people. In vivo measurement of the bremsstrahlung radiation produced by
incorporated pure-beta emitters can offer a rapid technique for the determination
of such radionuclides in the human body. This work presents a method for the
calibration of spectrometers, based on the use of UPh-02T (so-called IGOR)
phantom and specific (90)Sr/(90)Y sources, which can account for recent as well
as previous contaminations. The process of the whole- and partial-body counter
calibration in combination with application of a Monte Carlo code offers readily
extension also to other pure-beta emitters and various exposure scenarios.
PMID- 26443548
TI - Promoting health and reducing costs: a role for reform of self-monitoring of
blood glucose provision within the National Health Service.
AB - AIM: To determine the cost-effectiveness of all options for the self-monitoring
of blood glucose funded by the National Health Service, providing guidance for
disinvestment and testing the hypothesis that advanced meter features may justify
higher prices. METHODS: Using data from the Health and Social Care Information
Centre concerning all 8 340 700 self-monitoring of blood glucose-related
prescriptions during 2013/2014, we conducted a cost-minimization analysis,
considering both strip and lancet costs, including all clinically equivalent
technologies for self-monitoring of blood glucose, as determined by the ability
to meet ISO-15197:2013 guidelines for meter accuracy. RESULTS: A total of 56
glucose monitor, test strip and lancet combinations were identified, of which 38
met the required accuracy standards. Of these, the mean (range) net ingredient
costs for test strips and lancets were L0.27 (L0.14-L0.32) and L0.04 (L0.02
L0.05), respectively, resulting in a weighted average of L0.28 (L0.18-L0.37) per
test. Systems providing four or more advanced features were priced equal to those
providing just one feature. A total of L12 m was invested in providing 42 million
self-monitoring of blood glucose tests with systems that fail to meet acceptable
accuracy standards, and efficiency savings of L23.2 m per annum are achievable if
the National Health Service were to disinvest from technologies providing lesser
functionality than available alternatives, but at a much higher price.
CONCLUSION: The study uncovered considerable variation in the price paid by the
National Health Service for self-monitoring of blood glucose, which could not be
explained by the availability of advanced meter features. A standardized approach
to self-monitoring of blood glucose prescribing could achieve significant
efficiency savings for the National Health Service, whilst increasing overall
utilisation and improving safety for those currently using systems that fail to
meet acceptable standards for measurement accuracy.
PMID- 26443550
TI - Toward the discovery of dual HCMV-VZV inhibitors: Synthesis, structure activity
relationship analysis, and cytotoxicity studies of long chained 2-uracil-3-yl-N
(4-phenoxyphenyl)acetamides.
AB - The need for novel therapeutic options to fight herpesvirus infections still
persists. Herein we report the design, synthesis and antiviral evaluation of a
new family of non-nucleoside antivirals, derived from 1-[omega-(4
bromophenoxy)alkyl]uracil derivatives--previously reported inhibitors of human
cytomegalovirus (HCMV). Introduction of the N-(4-phenoxyphenyl)acetamide side
chain at N(3) increased their potency and widened activity spectrum. The most
active compounds in the series exhibit submicromolar activity against different
viral strains of HCMV and varicella zoster virus (VZV) replication in HEL cell
cultures. Inactivity against other DNA and RNA viruses, including herpes simplex
virus 1/2, points to a novel mechanism of antiviral action.
PMID- 26443549
TI - Antiviral activity of benzotriazole derivatives. 5-[4-(Benzotriazol-2-yl)phenoxy]
2,2-dimethylpentanoic acids potently and selectively inhibit Coxsackie Virus B5.
AB - A library of 64 benzotriazole derivatives (17 of which were [4-(benzotriazol-2
yl)phenoxy]alkanoic acids) were screened for antiviral activity against a panel
of twelve DNA and RNA viruses. Twenty-six compounds (12 of which were [4
(benzotriazol-2-yl)phenoxy]alkanoic acids) displayed activity against one or more
viruses. CVB-5, RSV, BVDV, Sb-1 and YFV were, in decreasing order, the more
frequently and effectively affected viruses; DENV-2, WNV, HIV-1 and Reo-1 were
only occasionally and modestly affected, while the remaining viruses were not
affected by any of the tested compounds. Worth of note were compounds 33 and 35;
the former for the activity against Sb-1 (EC50=7 MUM) and the latter for the
large spectrum of activity including six viruses with a mean EC50=12 MUM. Even
more interesting were the alkanoic acids 45-48 and 50-57 for their activity
against RSV and/or CVB-5. In particular, compound 56 displayed a potent and
selective activity against CVB-5 with EC50=0.15 MUM and SI=100, thus representing
a valuable hit compound for the development of antiviral agents for the treatment
of human pathologies related to this virus.
PMID- 26443552
TI - Growth parameter design for homogeneous material composition in ternary Ga(x)In(1
x)P nanowires.
AB - Ternary nanowires (NWs) often exhibit varying material composition along the NW
growth axis because of different diffusion properties of the precursor molecules.
This constitutes a problem for optoelectronic devices for which a homogeneous
material composition is most often of importance. Especially, ternary GaInP NWs
grown under a constant Ga-In precursor ratio typically show inhomogeneous
material composition along the length of the NW due to the complexity of low
temperature precursor pyrolysis and relative rates of growth species from gas
phase diffusion and surface diffusion that contribute to synthesis of particle
assisted growth. Here, we present the results of a method to overcome this
challenge by in situ tuning of the trimethylindium molar fraction during growth
of ternary Zn-doped GaInP NWs. The NW material compositions were determined by
use of x-ray diffraction, scanning transmission electron microscopy and energy
dispersive x-ray spectroscopy and the optical properties by photoluminescence
spectroscopy.
PMID- 26443551
TI - Ethanol inhibits gamma-secretase proteolytic activity in vascular smooth muscle
cells.
AB - BACKGROUND: Ethanol (EtOH) inhibits Notch-mediated vascular smooth muscle cell
(SMC) proliferation, an event that is key in vessel remodeling and atherogenesis.
The object of this study was to determine whether EtOH inhibits Notch signaling
in SMC at the level of gamma-secretase, a protease that in concert with alpha
secretase catalyzes the release of the intracellular domain of the Notch receptor
necessary for signaling. METHODS: Human coronary artery SMCs (HCASMCs) were
treated with a recombinant soluble Notch ligand, Delta-like ligand 4 (DLL4) (2
MUg/ml), or transfected with a constitutively active Notch 1 intracellular domain
(N1ICD), in the absence or presence of EtOH. EtOH (25 mM) treatment inhibited
DLL4-stimulated CBF-1/RBP-Jk-dependent promoter activity (determined by
luciferase assay) and downstream target gene HRT-3 mRNA levels. In contrast, EtOH
had no effect on N1ICD-driven CBF-1/RBP-Jk-dependent promoter activity or HRT-3
expression. RESULTS: These data suggest that EtOH inhibits Notch signaling at, or
prior to, Notch intracellular domain (NICD) generation. gamma-Secretase activity
was determined in solubilized membrane preparations from HCASMC treated
with/without EtOH (25 mM) or the gamma-secretase inhibitor DAPT (20 MUM) using
(i) a fluorometric assay and (ii) Western blot detection of cleavage products
using a Flag-tagged Notch-based substrate, N100Flag. EtOH inhibited basal and
DLL4-stimulated gamma-secretase activity, and SMC growth to a similar extent as
DAPT, whereas it had no effect on alpha-secretase (TACE/ADAM17) activity also
determined by fluorometric assay. Moreover, EtOH treatment inhibited the
expression of caveolin-1, a lipid raft protein implicated in regulating gamma
secretase activity, and altered its cellular distribution in HCASMC. CONCLUSIONS:
EtOH inhibits Notch signaling in vascular SMCs at the level of gamma-secretase
activity, possibly by affecting lipid raft function. Such a response might be
expected to result in attenuation of pathologic vessel remodeling and thus may
contribute to moderate alcohols' cardioprotective effects.
PMID- 26443553
TI - Synthesis of novel polymerizable molecules bearing bisphosphonate.
AB - In recent years, bisphosphonate chemistry has undergone an exponential growth due
to the potential applications of these compounds in medicine and nanobiomaterial
research. In this paper we describe the synthesis methods of different families
of methacrylic monomers bearing a bisphosphonate with varying lengths of the
chain, PEG linkers and more or less hydrolysable functions such as ester,
carbamate or amide.
PMID- 26443554
TI - Managing Suicidal Patients in the Emergency Department.
PMID- 26443555
TI - Development of a Hospital Standardized Mortality Ratio for Emergency Department
Care.
AB - STUDY OBJECTIVE: Experts have recommended including measures of mortality in
emergency department (ED) performance evaluation frameworks. This study aims to
develop a hospital standardized mortality ratio (HSMR) for patients admitted to
the hospital with conditions for which ED care may reduce mortality (emergency
sensitive conditions). METHODS: Data were extracted from Canadian hospital
discharge databases from April 1, 2009, to March 31, 2012. The ED HSMR is the
ratio of the observed deaths among patients with emergency-sensitive conditions
in a hospital during a year to the expected deaths for the same patients during
the reference year (2009-2010). The expected deaths were estimated with
predictive models fitted for different hospital peer groups (teaching hospitals
and large, medium, and small community hospitals). RESULTS: The data set included
1,770,809 admissions (9.2% deaths). The ED HSMR was calculated for 47% (294/629)
of all Canadian hospitals. The majority of exclusions (98%) were for small
community hospitals with fewer than 20 expected deaths. Predictive models had
good calibration and discrimination, with areas under the curve ranging from 0.80
to 0.81. In comparisons of 2010-2011 and 2011-2012, the classification of
hospitals by ED HSMR quartile was stable, with the majority remaining within the
same quartile (43.5%) or moving up or down a single quartile (40.2%). Peer-group
level comparisons between ED HSMR measured at different points after admission
(2, 7, and 30 days, and hospital discharge) did not demonstrate any significant
differences. CONCLUSION: The ED HSMR appears to be a reliable measure with high
discrimination, calibration, and forecasting properties that can be used to guide
assessment of ED performance.
PMID- 26443556
TI - Response to Letter to the Editor re: 'Movement-based subgrouping in low back
pain: synergy and divergence in approaches'.
PMID- 26443557
TI - Parent Engagement With a Telehealth-Based Parent-Mediated Intervention Program
for Children With Autism Spectrum Disorders: Predictors of Program Use and Parent
Outcomes.
AB - BACKGROUND: There has been growing interest in using telehealth to increase
access to parent-mediated interventions for children with ASD. However, little is
known about how parents engage with such programs. OBJECTIVE: This paper presents
program engagement data from a pilot study comparing self-directed and therapist
assisted versions of a novel telehealth-based parent-mediated intervention for
young children with autism spectrum disorders (ASD). METHODS: Parents of young
children with ASD were randomly assigned to receive a self-directed or therapist
assisted version of ImPACT Online. Parent engagement and satisfaction with the
different components of the program website were examined using the program's
automated data collection and a post-treatment evaluation survey. We examined the
relationship between program engagement and changes in parent knowledge and
implementation and participant characteristics associated with program
engagement. RESULTS: Of the 27 parent participants, the majority were female
(26/27, 96%), married (22/27, 81%), with a college degree or higher (18/27, 66%),
and less than half were employed outside of the home (10/27, 37%). The mean
chronological age of the child participants was 43.26 months, and the majority
were male (19/27, 70%) and white (21/27, 78%). Most of the families (19/27, 70%)
resided in a rural or medically underserved area. Parents logged into the website
an average of 46.85 times, spent an average of 964.70 minutes on the site, and
completed an average of 90.17% of the lesson learning activities. Participants in
the therapist-assisted group were more likely to engage with the website than
those in the self-directed group: F2,24=17.65, P<.001. In total, 85% of
participants completed the program, with a significantly greater completion rate
in the therapist-assisted group (N=27): chi(2) 1=5.06, P=.03. Lesson learning
activities were visited significantly more often than the supplemental activities
(all Ps<.05). Multiple regression controlling for pretreatment performance
indicated that program completion (beta=.51, P=.02) predicted post-treatment
intervention knowledge, and program completion (beta=.43, P=.03) and group
assignment (beta=-.37, P=.045) predicted post-treatment intervention fidelity.
Partial correlations indicated that parent depressive symptoms at pretreatment
were negatively associated with program completion (r=-.40, P=.04), but other key
parent and child demographic factors were not. Post-treatment measures of website
usability (r=.65, P<.001), treatment acceptability (r=.58, P=.002), and overall
satisfaction (r=.58, P=.002) were all related to program completion. CONCLUSIONS:
Parent engagement and satisfaction with ImPACT Online was high for both self
directed and therapist-assisted versions of the program, although therapist
assistance increased engagement. Program completion was associated with parent
outcomes, providing support for the role of the website in parent learning. This
program has the potential to increase access to parent-mediated intervention for
families of children with ASD.
PMID- 26443559
TI - Ten-year retrospective review of transfusion practices in beating-heart organ
donors.
AB - BACKGROUND: Recent studies suggest that restrictive transfusion strategies are
equivocal or noninferior to liberal strategies in various patient populations;
however, evidence for the optimal transfusion threshold or current transfusion
practice in beating-heart organ donors is lacking. A 10-year retrospective
analysis of blood product utilization in beating-heart organ donors was performed
to determine current transfusion practice. STUDY DESIGN AND METHODS: An
institutional review board-approved retrospective review of 439 beating-heart
organ donors from January 1, 2004, to October 1, 2014, was performed. For each
donor, hemoglobin (Hb), platelet (PLT), prothrombin time/international normalized
ratio (PT/INR), and fibrinogen levels as well as all transfusion reaction reports
were recorded from the time of declaration of brain death to organ procurement.
RESULTS: Red blood cell transfusion occurred in 304 donors (69.2%), with a trough
Hb level of more than 8 g/dL in 63.2% and more than 10 g/dL in 15.8%; final Hb
was more than 10 g/dL in 44.1% of transfused donors. PLT transfusion occurred in
165 donors (37.6%), with a trough PLT count of more than 50 * 10(9) /L in 113
(68.5%) and more than 100 * 10(9) /L in 15 (9.1%). Plasma transfusion occurred in
217 donors (49.4%), with a peak INR of less than 1.5 in 75 donors (34.6%) and a
peak INR of 1.6 to 2.0 in 112 donors (51.6%). Only 17.4% of donors who received
cryoprecipitate had fibrinogen levels measured, and results were all more than
200 mg/dL. Transfusion reactions were underreported (p = 0.0001). CONCLUSIONS:
This study suggests potential suboptimal use of limited biologic resources in
beating-heart organ donors, as well as significant underreporting of suspected
transfusion reactions. Additional studies are indicated to determine optimal
transfusion thresholds in this population.
PMID- 26443558
TI - Epidemiologic trends in medically-attended tree stand fall injuries among
Wisconsin deer hunters.
AB - BACKGROUND: Tree stand falls are the most common injury to hunters in the USA,
but there is limited research on the topic. This study examined the 5-year trends
in incident tree stand fall injuries in rural north-central Wisconsin and
described patient demographics and injury features. METHODS: A retrospective
analysis was conducted on five prior hunting seasons, 2009-2013. Cases were
ascertained from electronic health records via natural language processing that
identified patients from the Marshfield Epidemiologic Study Area who received
medical attention for a tree stand fall. Annual incidence rates were calculated
using the number of hunting license holders in the target population, per
administrative data from the Wisconsin Department of Natural Resources. RESULTS:
There were 16,556-16,902 deer hunters in any given year, with 39 (92% male)
confirmed medically-attended tree stand fall injuries in 2009-2013. Injuries
mainly occurred in the lower extremities (n=23), and included two fatalities and
one paralysis case. The risk of tree stand fall injuries went from 6.0 (95% CI:
3.2, 11.1) per 10,000 hunters in 2009 to 3.6 (95% CI: 1.6, 7.9) per 10,000
hunters in 2013, which was not a significant change over 5 years (p=0.79). Most
falls occurred among archery hunters, in the evening and when descending from a
tree stand. Cases were demographically similar to the general population of
Wisconsin deer hunters. CONCLUSIONS: The current seasonal incidence rate of tree
stand fall injuries is relatively low in rural Wisconsin, but with limited signs
of improvement. Continued efforts are needed to promote the long-term safety of
the hunting public.
PMID- 26443560
TI - Clinical Features and outcomes in adults with cardiogenic shock supported by
extracorporeal membrane oxygenation.
AB - Extracorporeal membrane oxygenation (ECMO) is an increasingly used supportive
measure for patients with refractory cardiogenic shock (CS). Despite its
increasing use, there remain minimal data regarding which patients with
refractory CS are most likely to benefit from ECMO. We retrospectively studied
all patients (n = 123) who underwent initiation of ECMO for CS from February 2009
to September 2014 at a single center. Baseline patient characteristics, including
demographics, co-morbid illness, cause of CS, available laboratory values, and
patient outcomes were analyzed. Overall, 69 patients (56%) were weaned from ECMO,
with 48 patients (39%) surviving to discharge. Survivors were younger (50 vs 60
years; p <=0.0001), had a lower rate of previous smoking (27 vs 56%; p = 0.01)
and chronic kidney disease (2% vs 13%; p = 0.03), and had lower lactate measured
soon after ECMO initiation (3.1 vs 10.2 mmol/l; p = 0.01). Patients with
pulmonary embolism (odds ratio 8.0, 95% confidence interval 2.00 to 31.99; p =
0.01) and acute cardiomyopathy (odds ratio 7.5, 95% confidence interval 1.69 to
33.27; p = 0.01) had a higher rate of survival than acute myocardial infarction,
chronic cardiomyopathy, and miscellaneous etiologies compared to postcardiotomy
CS as a referent. In conclusion, survival after ECMO initiation differs based on
underlying cause of CS. Survival may be lower in older patients and those with
early evidence of persistent hypoperfusion after initiation of ECMO for CS.
PMID- 26443561
TI - Comparison of Estimations Versus Measured Oxygen Consumption at Rest in Patients
With Heart Failure and Reduced Ejection Fraction Who Underwent Right-Sided Heart
Catheterization.
AB - Cardiac output during right-sided heart catheterization is an important variable
for patient selection of advanced therapies (cardiac transplantation and left
ventricular assist device implantation). The Fick method to determine cardiac
output is commonly used and typically uses estimated oxygen consumption (VO2)
from 1 of 3 published empirical formulas. However, these estimation equations
have not been validated in patients with heart failure and reduced ejection
fraction (HFrEF). The objectives of the present study were to determine the
accuracy of 3 equations for estimating VO2 compared with direct measurement of
VO2 and determine the extent clinically significant error occurred in calculating
cardiac output of patients with HFrEF. Breath-by-breath measurements of VO2 from
44 patients who underwent cardiac catheterization (66% men; age, 65 +/- 11 years,
left ventricular ejection fraction, 22 +/- 6%) were compared with the derived
estimations of LaFarge and Miettinen, Dehmer et al, and Bergstra et al. Single
sample t tests found only the mean difference between the estimation of LaFarge
and Miettinen and the measured VO2 to be nonsignificant (-10.3 ml/min +/- 6.2 SE,
p = 0.053). Bland-Altman plots demonstrated unacceptably large limits of
agreement for all equations. The rate of >=25% error in the equations by LaFarge
and Miettinen, Dehmer et al, and Bergstra et al occurred in 11%, 23%, and 45% of
patients, respectively. Misclassification of cardiac index derived from each
equation for 2 clinically important classifications: cardiogenic shock-21%, 23%,
and 32% and hypoperfusion-16%, 16%, and 25%; respectively. In conclusion, these
findings do not support the use of these empiric formulas to estimate the VO2 at
rest in patients with HFrEF who underwent right-sided heart catheterization.
PMID- 26443562
TI - Interdisciplinary Discrepancies Between Parenteral Nutrition Macronutrient
Prescribing and Recommendations: Is Body Mass Index a Factor?
AB - BACKGROUND: Formal nutrition training in medical schools and residencies is
lacking and needed. Registered dietitians (RDs) are formally trained in nutrition
support and considered experts in the nutrition field. Our purpose was to examine
prescribing and recommending discrepancies of parenteral nutrition macronutrients
between medical residents (MRs) and RDs and compare results with the ASPEN
clinical care guidelines. We also looked at discrepancies among obese patients,
due to their increased risk of mortality. MATERIALS AND METHODS: The primary end
point of this retrospective review was discrepancies in nonprotein calories
(NPCs) and grams of protein (PRO) between MRs and RDs. The secondary end point
was discrepancies in NPCs and PRO between MRs and RDs among patients stratified
by body mass index category. RESULTS: MRs prescribed 300 NPCs more versus RDs ( P
< .001). When compared with RDs, MRs prescribed fewer NPCs for underweight
patients and more for obese patients ( P < .001). The same analysis found that
the PRO discrepancies significantly varied by body mass index classification as
well ( P = .022). When these results were compared with the ASPEN clinical care
guidelines, RDs adhered closer to the guidelines than did MRs in terms of
permissive underfeeding of obese patients. CONCLUSION: It is widely accepted that
MRs are in need of increased formal training, and the results of our study
confirm this need and suggest a short-term solution of increasing order-writing
privileges for the RD. RDs with this privilege may adhere more closely to
clinical care guidelines and therefore increase patient safety.
PMID- 26443563
TI - The significance of lymphatic space invasion and its association with vascular
endothelial growth factor-C expression in ovarian cancer.
AB - The aim of this study is to investigate the significance of lymphatic space
invasion (LSI) and tumor VEGF-C expression in the lymphatic spread of ovarian
cancer. By performing immunostaining using human ovarian cancer specimens, we
first investigated the association between the extent of LSI and tumor VEGF-C
expression, tumor lymphangiogenesis, or the lymphatic metastasis. Moreover, by
performing in vitro and in vivo experiments, we elucidated the role of VEGF-C in
tumor lymphangiogenesis and lymph node metastasis as well as its role as a
therapeutic target in ovarian cancer. The presence of LSI was associated with
lymph node metastasis in patients with ovarian cancer. VEGF-C overexpression was
significantly associated with the increased LSI and LVD in ovarian cancer. VEGF-C
stimulated the lymphangiogenesis in vitro, induced the new lymph vessel
formation, and increased the lymph node metastasis in mice models of ovarian
cancer. The attenuation of VEGF-C expression by the treatment with mTORC1
inhibitor significantly inhibited lymphangiogenesis, and decreased lymph node
metastasis in mice models of ovarian cancer. The presence of LSI is an indicator
of nodal metastasis and is associated with higher tumor VEGF-C expression and
worse clinical outcome of ovarian cancer patients. VEGF-C plays a crucial role in
tumor lymphangiogenesis and lymph node metastasis of ovarian cancer.
PMID- 26443564
TI - Supramolecular Adducts of Cucurbit[7]uril and Amino Acids in the Gas Phase.
AB - The complexation of the macrocyclic cavitand cucurbit[7]uril (Q7) with a series
of amino acids (AA) with different side chains (Asp, Asn, Gln, Ser, Ala, Val, and
Ile) is investigated by ESI-MS techniques. The 1:1 [Q7 + AA + 2H](2+) adducts are
observed as the base peak when equimolar Q7:AA solutions are electrosprayed,
whereas the 1:2 [Q7 + 2AA + 2H](2+) dications are dominant when an excess of the
amino acid is used. A combination of ion mobility mass spectrometry (IM-MS) and
DFT calculations of the 1:1 [Q7 + AA + 2H](2+) (AA = Tyr, Val, and Ser) adducts
is also reported and proven to be unsuccessful at discriminating between
exclusion or inclusion-type conformations in the gas phase. Collision induced
dissociation (CID) revealed that the preferred dissociation pathways of the 1:1
[Q7 + AA + 2H](2+) dications are strongly influenced by the identity of the amino
acid side chain, whereas ion molecule reactions towards N-butylmethylamine
displayed a common reactivity pattern comprising AA displacement. Special
emphasis is given on the differences between the gas-phase behavior of the
supramolecular adducts with amino acids (AA = Asp, Asn, Gln, Ser, Ala, Val, and
Ile) and those featuring basic (Lys and Arg) and aromatic (Tyr and Phe) side
chains.
PMID- 26443565
TI - Multiple strokes associated with herpes simplex virus type-2 infection: case
report.
AB - Herpes simplex virus (HSV) type-2 is known to cause meningitis and usually runs a
benign course. Association of such infection with vasculitis of the central
nervous system is not well known. Presented here is a case initially diagnosed as
aseptic meningitis that subsequently evolved as stroke and exhibited angiographic
evidence of widespread vasculitis of the intracranial vessels in association with
a positive polymerase chain reaction (PCR) for HSV-2 in the cerebrospinal fluid
(CSF).
PMID- 26443566
TI - With better adjuvant therapy, does breast cancer stage still matter?
PMID- 26443567
TI - Methionine.
AB - This review focuses on the steps unique to methionine biosynthesis, namely the
conversion of homoserine to methionine. The past decade has provided a wealth of
information concerning the details of methionine metabolism and the review
focuses on providing a comprehensive overview of the field, emphasizing more
recent findings. Details of methionine biosynthesis are addressed along with key
cellular aspects, including regulation, uptake, utilization, AdoMet, the methyl
cycle, and growing evidence that inhibition of methionine biosynthesis occurs
under stressful cellular conditions. The first unique step in methionine
biosynthesis is catalyzed by the metA gene product, homoserine transsuccinylase
(HTS, or homoserine O-succinyltransferase). Recent experiments suggest that
transcription of these genes is indeed regulated by MetJ, although the repressor
binding sites have not yet been verified. Methionine also serves as the precursor
of S-adenosylmethionine, which is an essential molecule employed in numerous
biological processes. S-adenosylhomocysteine is produced as a consequence of the
numerous AdoMet-dependent methyl transfer reactions that occur within the cell.
In E. coli and Salmonella, this molecule is recycled in two discrete steps to
complete the methyl cycle. Cultures challenged by oxidative stress appear to
experience a growth limitation that depends on methionine levels. E. coli that
are deficient for the manganese and iron superoxide dismutases (the sodA and sodB
gene products, respectively) require the addition of methionine or cysteine for
aerobic growth. Modulation of methionine levels in response to stressful
conditions further increases the complexity of its regulation.
PMID- 26443568
TI - Mucosal Immune Responses to Escherichia coli and Salmonella Infections.
AB - The best-characterized mucosa-associated lymphoid tissue (MALT), and also the
most relevant for this review, is the gastrointestinal-associated lymphoid tissue
(GALT). The review reviews our understanding of the importance of mucosal immune
responses in resisting infections caused by E. coli and Salmonella spp. It
focuses on the major human E. coli infections and discusses whether antigen
specific mucosal immune responses are important for resistance against primary
infection or reinfection by pathogenic E. coli. It analyzes human data on mucosal
immunity against E. coli, a growing body of data of mucosal responses in food
production animals and other natural hosts of E. coli, and more recent
experimental studies in mice carrying defined deletions in genes encoding
specific immunological effectors, to show that there may be considerable
conservation of the effective host mucosal immune response against this pathogen.
The species Salmonella enterica contains a number of serovars that include
pathogens of both humans and animals; these bacteria are frequently host specific
and may cause different diseases in different hosts. Ingestion of various
Salmonella serovars, such as Typhimurium, results in localized infections of the
small intestine leading to gastroenteritis in humans, whereas ingestion of
serovar Typhi results in systemic infection and enteric fever. Serovar Typhi
infects only humans, and the review discusses the mucosal immune responses
against serovar Typhi, focusing on the responses in humans and in the mouse
typhoid fever model.
PMID- 26443569
TI - Meningitis-Associated Escherichia coli.
AB - Escherichia coliis the most common Gram-negative organism causing neonatal
meningitis. Neonatal E. colimeningitis continues to be an important cause of
mortality and morbidity throughout the world. Our incomplete knowledge of its
pathogenesis and pathophysiology contributes to such mortality and morbidity.
Recent reports of neonatal meningitis caused by E. coli strains producing CTX-M
type or TEM-type extended-spectrum beta-lactamases create a challenge. E.
colipenetration into the brain, the essential step in the development of E. coli
meningitis, requires a high-degree of bacteremia and penetration of the blood
brain barrier as live bacteria, but the underlying mechanisms remain incompletely
understood. Recent functional genomic approaches of meningitis-causing E. coli in
both in vitro and in vivo models of the blood-brain barrier (e.g., human brain
microvascular endothelial cells and animal models of experimental hematogenousE.
colimeningitis, respectively) have identified several E. coli factors
contributing to a high-degree of bacteremia, as well as specific microbial
factors contributing to E. coli invasion of the blood-brain barrier. In addition,
E. coli penetration of the blood-brain barrier involves specific host factors as
well as microbe- and host-specific signaling molecules. Blockade of such
microbial and host factors and host cell signaling molecules is efficient in
preventing E. coli penetration into the brain. Continued investigation of the
microbial and host factors contributing to E. colibacteremia andinvasion of the
blood-brain barrier is likely to identify new targets for prevention and therapy
of E. coli meningitis, thereby limiting the exposure to emerging antimicrobial
resistant E. coli.
PMID- 26443570
TI - Heat-Labile Enterotoxins.
AB - Heat-labile enterotoxins (LTs) of Escherichia coli are closely related to cholera
toxin (CT), which was originally discovered in 1959 in culture filtrates of the
gram-negative bacterium Vibrio cholerae. Several other gram-negative bacteria
also produce enterotoxins related to CT and LTs, and together these toxins form
the V. cholerae-E. coli family of LTs. Strains of E. coli causing a cholera-like
disease were designated enterotoxigenic E. coli (ETEC) strains. The majority of
LTI genes (elt) are located on large, self-transmissible or mobilizable plasmids,
although there are instances of LTI genes being located on chromosomes or carried
by a lysogenic phage. The stoichiometry of A and B subunits in holotoxin requires
the production of five B monomers for every A subunit. One proposed mechanism is
a more efficient ribosome binding site for the B gene than for the A gene,
increasing the rate of initiation of translation of the B gene independently from
A gene translation. The three-dimensional crystal structures of representative
members of the LT family (CT, LTpI, and LTIIb) have all been determined by X-ray
crystallography and found to be highly similar. Site-directed mutagenesis has
identified many residues in the CT and LT A subunits, including His44, Val53,
Ser63, Val97, Glu110, and Glu112, that are critical for the structures and
enzymatic activities of these enterotoxins. For the enzymatically active A1
fragment to reach its substrate, receptor-bound holotoxin must gain access to the
cytosol of target cells.
PMID- 26443571
TI - Virulence Gene Regulation in Escherichia coli.
AB - Escherichia colicauses three types of illnesses in humans: diarrhea, urinary
tract infections, and meningitis in newborns. The acquisition of virulence
associated genes and the ability to properly regulate these, often horizontally
transferred, loci distinguishes pathogens from the normally harmless commensal E.
coli found within the human intestine. This review addresses our current
understanding of virulence gene regulation in several important diarrhea-causing
pathotypes, including enteropathogenic, enterohemorrhagic,enterotoxigenic, and
enteroaggregativeE. coli-EPEC, EHEC, ETEC and EAEC, respectively. The intensely
studied regulatory circuitry controlling virulence of uropathogenicE. coli, or
UPEC, is also reviewed, as is that of MNEC, a common cause of meningitis in
neonates. Specific topics covered include the regulation of initial attachment
events necessary for infection, environmental cues affecting virulence gene
expression, control of attaching and effacing lesionformation, and control of
effector molecule expression and secretion via the type III secretion systems by
EPEC and EHEC. How phage control virulence and the expression of the Stx toxins
of EHEC, phase variation, quorum sensing, and posttranscriptional regulation of
virulence determinants are also addressed. A number of important virulence
regulators are described, including the AraC-like molecules PerA of EPEC, CfaR
and Rns of ETEC, and AggR of EAEC;the Ler protein of EPEC and EHEC;RfaH of
UPEC;and the H-NS molecule that acts to silence gene expression. The regulatory
circuitry controlling virulence of these greatly varied E. colipathotypes is
complex, but common themes offerinsight into the signals and regulators necessary
forE. coli disease progression.
PMID- 26443572
TI - Salmonella and Enteropathogenic Escherichia coli Interactions with Host Cells:
Signaling Pathways.
AB - The host-pathogen interaction involves a myriad of initiations and responses from
both sides. Bacterial pathogens such as enteropathogenic Escherichia coli (EPEC)
and Salmonella enterica have numerous virulence factors that interact with and
alter signaling components of the host cell to initiate responses that are
beneficial to pathogen survival and persistence. The study of Salmonella and EPEC
infection reveals intricate connections between host signal transduction,
cytoskeletal architecture, membrane trafficking, and cytokine gene expression.
The emerging picture includes elements of molecular mimicry by bacterial
effectors and bacterial subversion of typical host events, with the result that
EPEC is able to survive and persist in an extracellular milieu, while Salmonella
establishes an intracellular niche and is able to spread systemically throughout
the host. This review focuses on recent advances in our understanding of the
signaling events stemming from the host-pathogen interactions specific to
Salmonella and EPEC.
PMID- 26443573
TI - Modulation of Iron Availability at the Host-Pathogen Interface in Phagocytic
Cells.
AB - This review summarizes recent data on iron metabolism in macrophages, with a
special emphasis on possible bacteriostatic and bactericidal consequences for
intracellular pathogens. It includes the role of biological chelators and
transporters in normal macrophage physiology and antimicrobial defense. Iron is
an essential metal cofactor for many biochemical pathways in mammals. However,
excess iron promotes the formation of cytotoxic oxygen derivatives so that
systemic iron levels must be tightly regulated. The mechanism of iron recycling
by macrophages including iron efflux from erythrocyte-containing phagosomes, iron
release from macrophages, and entry into the transferrin (Tf) cycle remain poorly
understood. Ferroportin expression in the liver, spleen, and bone marrow cells
appears to be restricted to macrophages. Mutant mice bearing a conditional
deletion of the ferroportin gene in macrophages show retention of iron by hepatic
Kupffer cells and splenic macrophages. Hepcidin is induced by lipopolysaccharide
(LPS) in mouse spleens and splenic macrophage in vitro and appears to mediate the
LPS-induced down-regulation of ferroportin in the intestine and in splenic
macrophages, suggesting that inflammatory agents may regulate iron metabolism
through modulation of ferroportin expression. The host transporter Nramp1 may
compete directly with bacterial divalent-metal transport systems for the
acquisition of divalent metals within the phagosomal space. The ultimate outcome
of these competing interactions influences the ability of pathogens to survive
and replicate intracellularly. This seems particularly relevant to the
Salmonella, Leishmania, and Mycobacterium spp., in which inactivating mutations
in Nramp1 abrogate the natural resistance of macrophages to these pathogens.
PMID- 26443574
TI - Biosynthesis and Regulation of the Branched-Chain Amino Acids?.
AB - This review focuses on more recent studies concerning the systems biology of
branched-chain amino acid biosynthesis, that is, the pathway-specific and global
metabolic and genetic regulatory networks that enable the cell to adjust branched
chain amino acid synthesis rates to changing nutritional and environmental
conditions. It begins with an overview of the enzymatic steps and metabolic
regulatory mechanisms of the pathways and descriptions of the genetic regulatory
mechanisms of the individual operons of the isoleucine-leucine-valine (ilv)
regulon. This is followed by more-detailed discussions of recent evidence that
global control mechanisms that coordinate the expression of the operons of this
regulon with one another and the growth conditions of the cell are mediated by
changes in DNA supercoiling that occur in response to changes in cellular energy
charge levels that, in turn, are modulated by nutrient and environmental signals.
Since the parallel pathways for isoleucine and valine biosynthesis are catalyzed
by a single set of enzymes, and because the AHAS-catalyzed reaction is the first
step specific for valine biosynthesis but the second step of isoleucine
biosynthesis, valine inhibition of a single enzyme for this enzymatic step might
compromise the cell for isoleucine or result in the accumulation of toxic
intermediates. The operon-specific regulatory mechanisms of the operons of the
ilv regulon are discussed in the review followed by a consideration and brief
review of global regulatory proteins such as integration host factor (IHF), Lrp,
and CAP (CRP) that affect the expression of these operons.
PMID- 26443575
TI - Cytokines and Escherichia coli Sepsis.
AB - This review reviews the critical role played by cytokines in the pathogenesis of
Escherichia coli sepsis. It focuses on prototypic pro-inflammatory and anti
inflammatory cytokines and their influence on mortality in experimental animal
models of E. coli endotoxemia and of live E. coli sepsis. The review reviews the
results of clinical trials on anticytokine therapy in patients with severe sepsis
or septic shock. The recognition of the critical role played by tumor necrosis
factor (TNF), a secreted 17kDa cytokine, in endotoxic and gram-negative shock has
been a major step forward in our understanding of the pathogenesis of sepsis. The
review describes the role of TNF, IL1, and IL6 in animal models of E. coli
endotoxemia and sepsis. Given the pivotal role played by TNF in experimental
sepsis and the fact that elevated concentrations of TNF were detected in the
circulation of patients with sepsis, anti-TNF treatment strategies were
investigated as adjunctive therapy for severe sepsis and septic shock. Several
studies demonstrated that high levels of interleukin-6 (IL-6) are associated with
an increased risk for fatal outcome. Gamma interferon (IFN-gamma), IL-12, and IL
18 are functionally related cytokines. A recent study has indicated that
transgenic mice overexpressing IL-15 are resistant to an otherwise lethal
intraperitoneal E. coli challenge. IL4, IL10, and IL13are prototypic anti
inflammatory cytokines. Their classification as anti-inflammatory cytokines is
based on the observation that these molecules inhibit the production of
proinflammatory cytokines (primarily TNF and IL1) and toxic oxygen and reactive
nitrogen species by myeloid cells.
PMID- 26443576
TI - Adhesins of Enteropathogenic Escherichia coli.
AB - Enteropathogenic Escherichia coli (EPEC) strains induce morphological changes in
infected epithelial cells. The resulting attaching and effacing (A/E) lesion is
characterized by intimate bacterial adherence to epithelial cells, with
microvillus destruction, cytoskeletal rearrangement, and aggregation of host
cytoskeletal proteins. This review presents an overview of the adhesion
mechanisms used for the colonization of the human gastrointestinal tract by EPEC.
The mechanisms underlying EPEC adhesion, prior to and during the formation of the
A/E lesion, and the host cytosolic responses to bacterial infection leading to
diarrheal disease are discussed.
PMID- 26443577
TI - Detection of Delirium in Hospitalized Older General Medicine Patients: A
Comparison of the 3D-CAM and CAM-ICU.
AB - BACKGROUND: Delirium is common in older hospitalized patients and is associated
with poor outcomes, yet most cases go undetected. The best approach for
systematic delirium identification outside the intensive care unit remains
unknown. OBJECTIVE: To conduct a comparative effectiveness study of the Confusion
Assessment Method for the ICU (CAM-ICU) and the newly developed 3-minute
diagnostic assessment for delirium using the Confusion Assessment Method (3D-CAM)
in general medicine inpatients. DESIGN: Cross-sectional comparative effectiveness
study. SETTING: Two non-intensive care general medicine units at a single
academic medical center. PARTICIPANTS: Hospitalized general medicine patients
aged >=75 years. MEASUREMENTS: Clinicians performed a reference standard
assessment for delirium that included patient interviews, family interviews, and
review of the medical record. An expert panel determined the presence or absence
of delirium using DSM-IV criteria. Two blinded research assistants administered
the CAM-ICU and the 3D-CAM in random order, and we determined their diagnostic
test characteristics compared to the reference standard. RESULTS: Among the 101
participants (mean age 84 +/- 5.5 years, 61 % women, 25 % with dementia), 19 %
were classified as delirious based on the reference standard. Evaluation times
for the 3D-CAM and CAM-ICU were similar. The sensitivity [95 % confidence
interval (CI)] of delirium detection for the 3D-CAM was 95 % [74 %, 100 %] and
for the CAM-ICU was 53 % [29 %, 76 %], while specificity was >90 % for both
instruments. Subgroup analyses showed that the CAM-ICU had sensitivity of 30 % in
patients with mild delirium vs. 100 % for the 3D-CAM. CONCLUSIONS: In this
comparative effectiveness study, we found that the 3D-CAM had substantially
higher sensitivity than the CAM-ICU in hospitalized older general medicine
patients, and similar administration time. Therefore, the 3D-CAM may be a
superior screening tool for delirium in this patient population.
PMID- 26443579
TI - NADH as Donor.
AB - The number of NADH dehydrogenases and their role in energy transduction in
Escherchia coli have been under debate for a long time. Now it is evident that E.
coli possesses two respiratory NADH dehydrogenases, or NADH:ubiquinone
oxidoreductases, that have traditionally been called NDH-I and NDH-II. This
review describes the properties of these two NADH dehydrogenases, focusing on the
mechanism of the energy converting NADH dehydrogenase as derived from the high
resolution structure of the soluble part of the enzyme. In E. coli, complex I
operates in aerobic and anaerobic respiration, while NDH-II is repressed under
anaerobic growth conditions. The insufficient recycling of NADH most likely
resulted in excess NADH inhibiting tricarboxylic acid cycle enzymes and the
glyoxylate shunt. Salmonella enterica serovar Typhimurium complex I mutants are
unable to activate ATP-dependent proteolysis under starvation conditions. NDH-II
is a single subunit enzyme with a molecular mass of 47 kDa facing the cytosol.
Despite the absence of any predicted transmembrane segment it has to be purified
in the presence of detergents, and the activity of the preparation is stimulated
by an addition of lipids.
PMID- 26443578
TI - Peroxisome Proliferator Activated Receptor-alpha Association With Silent
Information Regulator 1 Suppresses Cardiac Fatty Acid Metabolism in the Failing
Heart.
AB - BACKGROUND: Heart failure is accompanied by changes in cardiac metabolism
characterized by reduced fatty acid (FA) utilization. However, the underlying
mechanism and its causative involvement in the progression of heart failure are
poorly understood. The peroxisome proliferator activated receptor-alpha
(PPARalpha)/retinoid X receptor (RXR) heterodimer promotes transcription of genes
involved in FA metabolism through binding to the PPAR response element, called
direct repeat 1 (DR1). Silent information regulator 1 (Sirt1) is a histone
deacetylase, which interacts with PPARalpha. METHODS AND RESULTS: To investigate
the role of PPARalpha in the impaired FA utilization observed during heart
failure, genetically altered mice were subjected to pressure overload. The DNA
binding of PPARalpha, RXRalpha, and Sirt1 to DR1 was evaluated with
oligonucleotide pull-down and chromatin immunoprecipitation assays. Although the
binding of PPARalpha to DR1 was enhanced in response to pressure overload, that
of RXRalpha was attenuated. Sirt1 competes with RXRalpha to dimerize with
PPARalpha, thereby suppressing FA utilization in the failing heart. DR1 sequence
analysis indicated that the typical DR1 sequence favors PPARalpha/RXRalpha
heterodimerization, whereas the switch from RXRalpha to Sirt1 takes place on
degenerate DR1s. Sirt1 bound to PPARalpha through a region homologous to the
PPARalpha binding domain in RXRalpha. A short peptide corresponding to the
RXRalpha domain not only inhibited the interaction between PPARalpha and Sirt1
but also improved FA metabolism and ameliorated cardiac dysfunction. CONCLUSIONS:
A change in the heterodimeric partner of PPARalpha from RXRalpha to Sirt1 is
responsible for the impaired FA metabolism and cardiac dysfunction in the failing
heart.
PMID- 26443580
TI - Biosynthesis of Hemes.
AB - This review is concerned specifically with the structures and biosynthesis of
hemes in E. coli and serovar Typhimurium. However, inasmuch as all tetrapyrroles
share a common biosynthetic pathway, much of the material covered here is
applicable to tetrapyrrole biosynthesis in other organisms. Conversely, much of
the available information about tetrapyrrole biosynthesis has been gained from
studies of other organisms, such as plants, algae, cyanobacteria, and anoxygenic
phototrophs, which synthesize large quantities of these compounds. This
information is applicable to E. coli and serovar Typhimurium. Hemes play
important roles as enzyme prosthetic groups in mineral nutrition, redox
metabolism, and gas-and redox-modulated signal transduction. The biosynthetic
steps from the earliest universal precursor, 5-aminolevulinic acid (ALA), to
protoporphyrin IX-based hemes constitute the major, common portion of the
pathway, and other steps leading to specific groups of products can be considered
branches off the main axis. Porphobilinogen (PBG) synthase (PBGS; also known as
ALA dehydratase) catalyzes the asymmetric condensation of two ALA molecules to
form PBG, with the release of two molecules of H2O. Protoporphyrinogen IX oxidase
(PPX) catalyzes the removal of six electrons from the tetrapyrrole macrocycle to
form protoporphyrin IX in the last biosynthetic step that is common to hemes and
chlorophylls. Several lines of evidence converge to support a regulatory model in
which the cellular level of available or free protoheme controls the rate of heme
synthesis at the level of the first step unique to heme synthesis, the formation
of GSA by the action of GTR.
PMID- 26443581
TI - Regulation of Fimbrial Expression.
AB - Fimbria-mediated interaction with the host elicits both innate and adaptive
immune responses, and thus their expression may not always be beneficial in vivo.
Furthermore, the metabolic drain of producing fimbriae is significant. It is not
surprising, therefore, to find that fimbrial production in Escherichia coli and
Salmonella enterica is under extensive environmental regulation. In many
instances, fimbrial expression is regulated by phase variation, in which
individual cells are capable of switching between fimbriate and afimbriate states
to produce a mixed population. Mechanisms of phase variation vary considerably
between different fimbriae and involve both genetic and epigenetic processes.
Notwithstanding this, fimbrial expression is also sometimes controlled at the
posttranscriptional level. In this chapter, we review key features of the
regulation of fimbrial gene expression in E. coli and Salmonella. The occurrence
and distribution of fimbrial operons vary significantly among E. coli pathovars
and even among the many Salmonella serovars. Therefore, general principles are
presented on the basis of detailed discussion of paradigms that have been
extensively studied, including Pap, type 1 fimbriae, and curli. The roles of
operon specific regulators like FimB or CsgD and of global regulatory proteins
like Lrp, CpxR, and the histone-like proteins H-NS and IHF are reviewed as are
the roles of sRNAs and of signalling nucleotide cyclic-di-GMP. Individual
examples are discussed in detail to illustrate how the regulatory factors
cooperate to allow tight control of expression of single operons. Molecular
networks that allow coordinated expression between multiple fimbrial operons and
with flagella in a single isolate are also presented. This chapter illustrates
how adhesin expression is controlled, and the model systems also illustrate
general regulatory principles germane to our overall understanding of bacterial
gene regulation.
PMID- 26443582
TI - Copper Homeostasis in Escherichia coli and Other Enterobacteriaceae.
AB - An interesting model for studying environmental influences shaping microbial
evolution is provided by a multitude of copper resistance and copper homeostasis
determinants in enteric bacteria. This review describes these determinants and
tries to relate their presence to the habitat of the respective organism, as a
current hypothesis predicts that the environment should determine an organism's
genetic makeup. In Escherichia coli there are four regulons that are induced in
the presence of copper. Two, the CueR and the CusR regulons, are described in
detail. A central component regulating intracellular copper levels, present in
all free-living enteric bacteria whose genomes have so far been sequenced, is a
Cu(I)translocating P-type ATPase. The P-type ATPase superfamily is a ubiquitous
group of proteins involved in the transport of charged substrates across
biological membranes. Whereas some components involved in copper homeostasis can
be found in both anaerobes and aerobes, multi-copper oxidases (MCOs) implicated
in copper tolerance in E. coli, such as CueO and the plasmid-based PcoA, can be
found only in aerobic organisms. Several features indicate that CueO, PcoA, and
other related MCOs are specifically adapted to combat copper-mediated oxidative
damage. In addition to these well-characterized resistance operons, there are
numerous other genes that appear to be involved in copper binding and trafficking
that have not been studied in great detail. SilE and its homologue PcoE, for
example, are thought to effect the periplasmic binding and sequestration of
silver and copper, respectively.
PMID- 26443583
TI - ATP Synthesis by Oxidative Phosphorylation.
AB - The F1F0-ATP synthase (EC 3.6.1.34) is a remarkable enzyme that functions as a
rotary motor. It is found in the inner membranes of Escherichia coli and is
responsible for the synthesis of ATP in response to an electrochemical proton
gradient. Under some conditions, the enzyme functions reversibly and uses the
energy of ATP hydrolysis to generate the gradient. The ATP synthase is composed
of eight different polypeptide subunits in a stoichiometry of
alpha3beta3gammadeltaepsilonab2c10. Traditionally they were divided into two
physically separable units: an F1 that catalyzes ATP hydrolysis
(alpha3beta3gammadeltaepsilon) and a membrane-bound F0 sector that transports
protons (ab2c10). In terms of rotary function, the subunits can be divided into
rotor subunits (gammaepsilonc10) and stator subunits (alpha3beta3deltaab2). The
stator subunits include six nucleotide binding sites, three catalytic and three
noncatalytic, formed primarily by the beta and alpha subunits, respectively. The
stator also includes a peripheral stalk composed of delta and b subunits, and
part of the proton channel in subunit a. Among the rotor subunits, the c subunits
form a ring in the membrane, and interact with subunit a to form the proton
channel. Subunits gamma and epsilon bind to the c-ring subunits, and also
communicate with the catalytic sites through interactions with alpha and beta
subunits. The eight subunits are expressed from a single operon, and
posttranscriptional processing and translational regulation ensure that the
polypeptides are made at the proper stoichiometry. Recent studies, including
those of other species, have elucidated many structural and rotary properties of
this enzyme.
PMID- 26443584
TI - Messenger RNA Decay.
AB - This chapter discusses several topics relating to the mechanisms of mRNA decay.
These topics include the following: important physical properties of mRNA
molecules that can alter their stability; methods for determining mRNA half
lives; the genetics and biochemistry of proteins and enzymes involved in mRNA
decay; posttranscriptional modification of mRNAs; the cellular location of the
mRNA decay apparatus; regulation of mRNA decay; the relationships among mRNA
decay, tRNA maturation, and ribosomal RNA processing; and biochemical models for
mRNA decay. Escherichia coli has multiple pathways for ensuring the effective
decay of mRNAs and mRNA decay is closely linked to the cell's overall RNA
metabolism. Finally, the chapter highlights important unanswered questions
regarding both the mechanism and importance of mRNA decay.
PMID- 26443585
TI - S- and N-Oxide Reductases.
AB - Escherichia coli is a versatile facultative anaerobe that can respire on a number
of terminal electron acceptors, including oxygen, fumarate, nitrate, and S- and N
oxides. Anaerobic respiration using S- and N-oxides is accomplished by enzymatic
reduction of these substrates by dimethyl sulfoxide reductase (DmsABC) and
trimethylamine N-oxide reductase (TorCA). Both DmsABC and TorCA are membrane
associated redox enzymes that couple the oxidation of menaquinol to the reduction
of S- and N-oxides in the periplasm. DmsABC is membrane bound and is composed of
a membrane-extrinsic dimer with a 90.4-kDa catalytic subunit (DmsA) and a 23.1
kDa electron transfer subunit (DmsB). These subunits face the periplasm and are
held to the membrane by a 30.8-kDa membrane anchor subunit (DmsC). The enzyme
provides the scaffold for an electron transfer relay composed of a quinol binding
site, five [4Fe-4S] clusters, and a molybdo-bis(molybdopterin guanine
dinucleotide) (present nomenclature: Mo-bis-pyranopterin) (Mo-bisMGD) cofactor.
TorCA is composed of a soluble periplasmic subunit (TorA, 92.5 kDa) containing a
Mo-bis-MGD. TorA is coupled to the quinone pool via a pentaheme c subunit (TorC,
40.4 kDa) in the membrane. Both DmsABC and TorCA require system-specific
chaperones (DmsD or TorD) for assembly, cofactor insertion, and/or targeting to
the Tat translocon. In this chapter, we discuss the complex regulation of the
dmsABC and torCAD operons, the poorly understood paralogues, and what is known
about the assembly and translocation to the periplasmic space by the Tat
translocon.
PMID- 26443586
TI - Salmonella as an Inducer of Autoimmunity.
AB - A clear etiological link has been established between infection with several gram
negative enteric pathogens, including Salmonella spp., and the incidence of
reactive arthritis (ReA), an autoimmune disease that largely affects the joints.
ReA is sometimes referred to as Reiter's syndrome, particularly when accompanied
by uveitis and urethritis. This review reviews the evidence etiologically linking
Salmonella infection with autoimmune disease and addresses the roles that
bacterial and host elements play in controlling disease outcome. ReA is an
autoimmune disease that largely consists of painful joint inflammation but also
can include inflammation of the eye, gastrointestinal tract, and skin. ReA is a
member of a broad spectrum of chronic inflammatory disorders termed the
seronegative spondyloarthropathies (SNSpAs) that includes ankylosing spondylitis
(AS), psoriatic arthritis, and enteropathic arthritis. Salmonella species, as
well as other enteric pathogens associated with postgastroenteritis ReA, are
facultative intracellular gram-negative bacteria. Many studies have analyzed the
association of the HLA class I molecule, HLA-B27, with SNSpAs. Whereas B27 has
been shown to be present in 90 to 95% of cases of AS, the association of the B27
haplotype with other SNSpAs is more tenuous. The clear association between ReA
and infection with Salmonella or other gram-negative enteric pathogens has led to
the suggestion that the adaptive immune response to infection has an autoimmune
component. In addition to various Salmonella species, other gram-negative enteric
pathogens have been linked to the development of ReA. Given their close
relationship to Salmonella, this review considers the involvement of Shigella
species in ReA.
PMID- 26443587
TI - Fimbriae: Classification and Biochemistry.
AB - Proteinaceous, nonflagellar surface appendages constitute a variety of
structures, including those known variably as fimbriae or pili. Constructed by
distinct assembly pathways resulting in diverse morphologies, fimbriae have been
described to mediate functions including adhesion, motility, and DNA transfer. As
these structures can represent major diversifying elements among Escherichia and
Salmonella isolates, multiple fimbrial classification schemes have been proposed
and a number of mechanistic insights into fimbrial assembly and function have
been made. Herein we describe the classifications and biochemistry of fimbriae
assembled by the chaperone/usher, curli, and type IV pathways.
PMID- 26443588
TI - Folate Biosynthesis, Reduction, and Polyglutamylation and the Interconversion of
Folate Derivatives.
AB - Many microorganisms and plants possess the ability to synthesize folic acid
derivatives de novo, initially forming dihydrofolate. All the folic acid
derivatives that serve as recipients and donors of one-carbon units are
derivatives of tetrahydrofolate, which is formed from dihydrofolate by an NADPH
dependent reduction catalyzed by dihydrofolate reductase (FolA). This review
discusses the biosynthesis of dihydrofolate monoglutamate, its reduction to
tetrahydrofolate monoglutamate, and the addition of glutamyl residues to form
folylpolyglutamates. Escherichia coli and Salmonella, like many microorganisms
that can synthesize folate de novo, appear to lack the ability to transport
folate into the cell and are thus highly susceptible to inhibitors of folate
biosynthesis. The review includes a brief discussion of the inhibition of folate
biosynthesis by sulfa drugs. The folate biosynthetic pathway can be divided into
two sections. First, the aromatic precursor chorismate is converted to
paminobenzoic acid (PABA) by the action of three proteins. Second, the pteridine
portion of folate is made from GTP and coupled to PABA to generate
dihydropteroate, and the bifunctional protein specified by folC, dihydrofolate
synthetase, or folylpolyglutamate synthetase, adds the initial glutamate molecule
to form dihydrofolate (H2PteGlu1, or dihydropteroylmonoglutamate). Bacteriophage
T4 infection of E. coli has been shown to cause alterations in the metabolism of
folate derivatives. Infection is associated with an increase in the chain lengths
in folylpolyglutamates and particularly the accumulation of hexaglutamate
derivatives.
PMID- 26443590
TI - Introduction and Perspectives.
AB - Classically, metabolism was investigated by studying molecular characteristics of
enzymes and their regulators in isolation. This reductionistic approach
successfully established mechanistic relationships with the immediate interacting
neighbors and allowed reconstruction of network structures. Severely
underdeveloped was the ability to make precise predictions about the integrated
operation of pathways and networks that emerged from the typically nonlinear and
complex interactions of proteins and metabolites. The burden of metabolic
engineering is a consequence of this fact-one cannot yet predict with any
certainty precisely what needs to be engineered to produce more complex
phenotypes. What was and still is missing are concepts, methods, and algorithms
to integrate data and information into a quantitatively coherent whole, as well
as theoretical concepts to reliably predict the consequence of environmental
stimuli or genetic interventions. This introduction and perspective to Domain 3,
Metabolism and Metabolic Fluxes, starts with a brief overview of the panoply of
global measurement technologies that herald the dawning of systems biology and
whose impact on metabolic research is apparent throughout the Domain 3. In the
middle section, applications to Escherichia coli are used to illustrate general
concepts and successes of computational methods that approach metabolism as a
network of interacting elements, and thus have potential to fill the gap in
quantitative data and information integration. The final section highlights
prospective focus areas for future metabolic research, including functional
genomics, eludication of evolutionary principles, and the integration of
metabolism with regulatory networks.
PMID- 26443591
TI - Biosynthesis of Proline.
AB - Proline was among the last biosynthetic precursors to have its biosynthetic
pathway unraveled. This review recapitulates the findings on the biosynthesis and
transport of proline. Glutamyl kinase (GK) catalyzes the ATP-dependent
phosphorylation of L-glutamic acid. Purification of gamma-GK from Escherichia
coli was facilitated by the expression of the proB and proA genes from a high
copy-number plasmid and the development of a specific coupled assay based on the
NADPH-dependent reduction of GP by gamma-glutamyl phosphate reductase (GPR). GPR
catalyzes the NADPH-dependent reduction of GP to GSA. Site directed mutagenesis
was used to identify residues that constitute the active site of E. coli GK. This
analysis indicated that there is an overlap between the binding sites for
glutamate and the allosteric inhibitor proline, suggesting that proline competes
with the binding of glutamate. The review also summarizes the genes involved in
the metabolism of proline in E. coli and Salmonella. Among the completed genomic
sequences of Enterobacteriaceae, genes specifying all three proline biosynthetic
enzymes can be discerned in E. coli, Shigella, Salmonella enterica, Serratia
marcescens, Erwinia carotovora, Yersinia, Photorhabdus luminescens, and Sodalis
glossinidius strain morsitans. The intracellular proline concentration increases
with increasing external osmolality in proline-overproducing mutants. This
apparent osmotic regulation of proline accumulation in the overproducing strains
may be the result of increased retention or recapture of proline, achieved by
osmotic stimulation of the ProP or ProU proline transport systems. A number of
proline analogs can be incorporated into proteins in vivo or in vitro.
PMID- 26443592
TI - How We Got to Where We Are: the Ribosome in the 21st Century.
AB - This article is a short, informal history of the ribosome field that begins with
the emergence of the field in the 1930s and ends with a description of its state
in 2007, the year this essay was written. The growth in our understanding of both
the role of the ribosome in protein synthesis and its structure is emphasized.
Starting in 2000, the field experienced a massive upheaval as a result of the
publication of the first atomic-resolution crystal structures for ribosomes.
However, by 2007, the field had recovered sufficiently so that one could begin to
understand how it was likely to evolve in its "poststructural" era. For that
reason, this essay is about as useful as a short history of the ribosome field
today as it was several years ago, when it was written.
PMID- 26443589
TI - Biosynthesis of Pantothenic Acid and Coenzyme A.
AB - Pantothenate is vitamin B5 and is the key precursor for the biosynthesis of
coenzyme A (CoA), a universal and essential cofactor involved in a myriad of
metabolic reactions, including the synthesis of phospholipids, the synthesis and
degradation of fatty acids, and the operation of the tricarboxylic acid cycle.
CoA is also the only source of the phosphopantetheine prosthetic group for
enzymes that shuttle intermediates between the active sites of enzymes involved
in fatty acid, nonribosomal peptide, and polyketide synthesis. Pantothenate can
be synthesized de novo and/or transported into the cell through a
pantothenatepermease. Pantothenate uptake is essential for those organisms that
lack the genes to synthesize this vitamin. The intracellular levels of CoA are
controlled by the balance between synthesis and degradation. In particular, CoA
is assembled in five enzymatic steps, starting from the phosphorylation of
pantothenate to phosphopantothenatecatalyzed by pantothenate kinase, the product
of the coaA gene. In some bacteria, the production of phosphopantothenate by
pantothenate kinase is the rate limiting and most regulated step in the
biosynthetic pathway. CoA synthesis additionally networks with other vitamin
associated pathways, such as thiamine and folic acid.
PMID- 26443593
TI - Succinate as Donor; Fumarate as Acceptor.
AB - Succinate and fumarate are four-carbon dicarboxylates that differ in the identity
of their central bond (single or double). The oxidoreduction of these small
molecules plays a central role in both aerobic and anaerobic respiration. During
aerobic respiration, succinate is oxidized, donating two reducing equivalents,
while in anaerobic respiration, fumarate is reduced, accepting two reducing
equivalents. Two related integral membrane Complex II superfamily members
catalyze these reactions, succinate:ubiquinone oxidoreductase (SQR) and
fumarate:menaquinol oxidoreductase (QFR). The structure, function, and regulation
of these integral-membrane enzymes are summarized here. The overall architecture
of these Complex II enzymes has been found to consist of four subunits: two
integral membrane subunits, and a soluble domain consisting of an iron-sulfur
protein subunit, and a flavoprotein subunit. This architecture provides a
scaffold that houses one active site in the membrane and another in the soluble
milieu, making a linear electron transfer chain that facilities shuttling of
reducing equivalents between the two active sites. A combination of kinetic
measurements, mutagenesis, electron paramagnetic resonance spectroscopy, UV/Vis
spectroscopy, and x-ray crystallography have suggested mechanisms for
succinate:fumarate interconversion, electron transfer, and quinone:quinol
interconversion. Of particular interest are the structural details that control
directionality and make SQR and QFR primed for preferential catalysis each in
different favored directions.
PMID- 26443595
TI - Progress toward improved therapies for inborn errors of metabolism.
AB - Because of their prevalence, severity and lack of effective treatments, inborn
errors of metabolism need novel and more effective therapeutic approaches. The
opportunity for an early treatment coming from expanded newborn screening has
made this need even more urgent. To meet this demand, a growing number of novel
treatments are entering in the phase of clinical development. Strategies to
overcome the detrimental consequences of the enzyme deficiencies responsible for
inborn errors of metabolism have been focused on multiple fronts at the levels of
the gene, RNA, protein and whole cell. These strategies have been accomplished
using a wide spectrum of approaches ranging from small molecules to enzyme
replacement therapy, cell and gene therapy. The applications of new technologies
in the field of inborn errors of metabolism, such as genome editing, RNA
interference and cell reprogramming, along with progress in pre-existing
strategies, such as gene therapy or cell transplantation, have tremendous
potential for clinical translation.
PMID- 26443596
TI - Advances in treatment of achondroplasia and osteoarthritis.
AB - Achondroplasia (ACH) is the prototype and most common of the human
chondrodysplasias. It results from gain-of-function mutations that exaggerate the
signal output of the fibroblast growth factor receptor 3 (FGFR3), a receptor
tyrosine kinase that negatively regulates growth plate activity and linear bone
growth. Several approaches to reduce FGFR3 signaling by blocking receptor
activation or inhibiting downstream signals have been proposed. Five show promise
in preclinical mouse studies. Two candidate therapies target the extracellular
domain of FGFR3. The first is a decoy receptor that competes for activating
ligands. The second is a synthetic blocking peptide that prevents ligands from
binding and activating FGFR3. Two established drugs, statins and meclozine,
improve growth of ACH mice. The strongest candidate therapy employs an analog of
C-type natriuretic peptide (CNP), which antagonizes the mitogen-activated-protein
(MAP) kinase pathway downstream of the FGFR3 receptor and may also act
independently in the growth plate. Only the CNP analog has reached clinical
trials. Preliminary results of Phase 2 studies show a substantial increase in
growth rate of ACH children after six months of therapy with no serious adverse
effects. A challenge for drug therapy in ACH is targeting agents to the avascular
growth plate. The application of gene therapy in osteoarthritis offers insights
because it faces similar technical obstacles. Major advances in gene therapy
include the emergence of recombinant adeno-associated virus as the vector of
choice, capsid engineering to target vectors to specific tissues, and development
of methods to direct vectors to articular chondrocytes.
PMID- 26443594
TI - Increased STAG2 dosage defines a novel cohesinopathy with intellectual disability
and behavioral problems.
AB - Next generation genomic technologies have made a significant contribution to the
understanding of the genetic architecture of human neurodevelopmental disorders.
Copy number variants (CNVs) play an important role in the genetics of
intellectual disability (ID). For many CNVs, and copy number gains in particular,
the responsible dosage-sensitive gene(s) have been hard to identify. We have
collected 18 different interstitial microduplications and 1 microtriplication of
Xq25. There were 15 affected individuals from 6 different families and 13
singleton cases, 28 affected males in total. The critical overlapping region
involved the STAG2 gene, which codes for a subunit of the cohesin complex that
regulates cohesion of sister chromatids and gene transcription. We demonstrate
that STAG2 is the dosage-sensitive gene within these CNVs, as gains of STAG2 mRNA
and protein dysregulate disease-relevant neuronal gene networks in cells derived
from affected individuals. We also show that STAG2 gains result in increased
expression of OPHN1, a known X-chromosome ID gene. Overall, we define a novel
cohesinopathy due to copy number gain of Xq25 and STAG2 in particular.
PMID- 26443597
TI - Prevention of abdominal aortic aneurysm progression by targeted inhibition of
matrix metalloproteinase activity with batimastat-loaded nanoparticles.
AB - RATIONALE: Matrix metalloproteinases (MMPs)-mediated extracellular matrix
destruction is the major cause of development and progression of abdominal aortic
aneurysms. Systemic treatments of MMP inhibitors have shown effectiveness in
animal models, but it did not translate to clinical success either because of low
doses used or systemic side effects of MMP inhibitors. We propose a targeted
nanoparticle (NP)-based delivery of MMP inhibitor at low doses to the abdominal
aortic aneurysms site. Such therapy will be an attractive option for preventing
expansion of aneurysms in patients without systemic side effects. OBJECTIVE: Our
previous study showed that poly(d,l-lactide) NPs conjugated with an antielastin
antibody could be targeted to the site of an aneurysm in a rat model of abdominal
aortic aneurysms. In the study reported here, we tested whether such targeted NPs
could deliver the MMP inhibitor batimastat (BB-94) to the site of an aneurysm and
prevent aneurysmal growth. METHODS AND RESULTS: Poly(d,l-lactide) NPs were loaded
with BB-94 and conjugated with an elastin antibody. Intravenous injections of
elastin antibody-conjugated BB-94-loaded NPs targeted the site of aneurysms and
delivered BB-94 in a calcium chloride injury-induced abdominal aortic aneurysms
in rats. Such targeted delivery inhibited MMP activity, elastin degradation,
calcification, and aneurysmal development in the aorta (269% expansion in control
versus 40% elastin antibody-conjugated BB-94-loaded NPs) at a low dose of BB-94.
The systemic administration of BB-94 alone at the same dose was ineffective in
producing MMP inhibition. CONCLUSIONS: Targeted delivery of MMP inhibitors using
NPs may be an attractive strategy to inhibit aneurysmal progression.
PMID- 26443598
TI - Soluble CD14: An Independent Biomarker for the Risk of Mother-to-Child
Transmission of HIV in a Setting of Preexposure and Postexposure Antiretroviral
Prophylaxis.
AB - Elevated soluble CD14 (sCD14) concentrations, a marker of monocyte activation,
predicts adverse outcomes in human immunodeficiency virus (HIV)-infected adults.
To examine the association of sCD14 concentrations with the risk of mother-to
child transmission (MTCT) of HIV, we nested a case-control study (49 pairs of
infants and their HIV-infected mothers) within the Six-Week Extended-Dose
Nevirapine trial. Median peripartum maternal log2 sCD14 concentration was higher
among transmitters (defined as pairs in which maternally transmitted HIV
infection occurred by 12 months of age) than nontransmitters (20.29 pg/mL vs
19.41 pg/mL; P = .005). There was an increased odds of MTCT for every log2
increase in maternal sCD14 concentration, after adjustment for maternal HIV load,
CD4 count and cART exposure (adjusted odds ratio, 3.51; 95% confidence interval,
1.21-10.21). Maternal monocyte activation may adversely influence the risk of
MTCT of HIV.
PMID- 26443599
TI - Delay and death-thought accessibility: a meta-analysis.
AB - The dual-process component of Terror Management Theory (TMT) proposes that
different types of threats lead to increases in death-thought accessibility (DTA)
after different delay intervals. Experimental studies of terror management
threats' effect on DTA were collected and coded for their use of explicitly death
related (vs. not explicitly death-related) threats, and for their use of delay
and task-switching during the delay. Results reveal that studies using death
related threats achieved larger DTA effect-sizes when they included more task
switching or a longer delay between the threat and the DTA measurement. In
contrast, studies using threats that were not explicitly death-related achieved
smaller DTA effect-sizes when they included more task-switching between the
threat and the DTA measurement. These findings provide partial support for the
dual-process component's predictions regarding delay and DTA. Limitations and
future directions are discussed.
PMID- 26443600
TI - Prospective Comparison between two different magnetic resonance defecography
techniques for evaluating pelvic floor disorders: air-balloon versus gel for
rectal filling.
AB - PURPOSE: to prospectively compare two rectal filling techniques for dynamic MRI
of pelvic floor disorders (PFD). METHODS AND MATERIALS: Twenty-six patients with
PFD underwent the two techniques during the same procedure, one based on rectal
placement of a balloon-catheter filled with saline and air insufflation (air
balloon technique or AB); another based on rectal filling with 180 cc of gel (gel
filling technique or GF). The examinations were compared for assessment and
staging of PFD, including rectal-descent, rectocele, cystocele, colpocele,
enterocele, rectal invagination. Surgery and clinical examinations were the gold
standard. RESULTS: AB showed sensitivity of 96 % for rectal descent, 100 % for
both rectocele and colpocele, 86 % for rectal invagination and 100 % for
enterocele; understaged 11 % of rectal descents and 19 % of rectoceles. GF showed
sensitivity of 100 % for rectal descent, 91 % for rectocele, 83 % for colpocele,
100 % for rectal invagination and 73 % for enterocele; understaged 3.8 % of
rectal descent and 11.5 % of rectoceles. Both techniques showed 100 % of
specificity. Agreement between air-balloon and gel filling was 84 % for rectal
descent, 69 % for rectocele, 88 % for rectal invagination, 84 % for enterocele,
88 % for cystocele and 92 % for colpocele. CONCLUSION: Both techniques allowed a
satisfactory evaluation of PFD. The gel filling was superior for rectal
invagination, the air-balloon for rectocele and anterior/middle compartment
disorders. KEY POINTS: * A standardized MRI technique for assessing pelvic floor
disorders is not yet established. * This study compares two MRI techniques based
on different rectal filling: air-balloon versus gel. * Both MRI techniques proved
to be valuable in assessing PFD, with good agreement. * Air-balloon technique is
more hygienic and better tolerated than the gel-filling technique. * Gel was
superior for rectal invagination, air-balloon for rectocele and uro-genital
prolapses.
PMID- 26443601
TI - Computer-aided detection of pulmonary nodules: a comparative study using the
public LIDC/IDRI database.
AB - OBJECTIVES: To benchmark the performance of state-of-the-art computer-aided
detection (CAD) of pulmonary nodules using the largest publicly available
annotated CT database (LIDC/IDRI), and to show that CAD finds lesions not
identified by the LIDC's four-fold double reading process. METHODS: The LIDC/IDRI
database contains 888 thoracic CT scans with a section thickness of 2.5 mm or
lower. We report performance of two commercial and one academic CAD system. The
influence of presence of contrast, section thickness, and reconstruction kernel
on CAD performance was assessed. Four radiologists independently analyzed the
false positive CAD marks of the best CAD system. RESULTS: The updated commercial
CAD system showed the best performance with a sensitivity of 82 % at an average
of 3.1 false positive detections per scan. Forty-five false positive CAD marks
were scored as nodules by all four radiologists in our study. CONCLUSIONS: On the
largest publicly available reference database for lung nodule detection in chest
CT, the updated commercial CAD system locates the vast majority of pulmonary
nodules at a low false positive rate. Potential for CAD is substantiated by the
fact that it identifies pulmonary nodules that were not marked during the
extensive four-fold LIDC annotation process. KEY POINTS: * CAD systems should be
validated on public, heterogeneous databases. * The LIDC/IDRI database is an
excellent database for benchmarking nodule CAD. * CAD can identify the majority
of pulmonary nodules at a low false positive rate. * CAD can identify nodules
missed by an extensive two-stage annotation process.
PMID- 26443602
TI - Diffusion-tensor-based method for robust and practical estimation of axial and
radial diffusional kurtosis.
AB - OBJECTIVES: A new method that can estimate diffusional kurtosis image (DKI),
estimated DKI (eDKI), parallel and perpendicular to neuronal fibres from greatly
limited image data was designed to enable quick and practical assessment of DKI
in clinics. The purpose of this study was to discuss the potential of this method
for clinical use. METHODS: Fourteen healthy volunteers were examined with a 3
Tesla MRI. The diffusion-weighting parameters included five different b-values
(0, 500, 1,500, 2,000 and 2,500 s/mm(2)) with 64 different encoding directions
for each of the b-values. K values were calculated by both conventional DKI
(convDKI) and eDKI from these complete data, and also from the data that the
encoding directions were abstracted to 32, 21, 15, 12 and 6. Error-pixel ratio
and the root mean square error (RMSE) compared with the standard were compared
between the methods (Wilcoxon signed-rank test: P < 0.05 was considered
significant). RESULTS: Error-pixel ratio was smaller in eDKI than in convDKI and
the difference was significant. In addition, RMSE was significantly smaller in
eDKI than in convDKI, or otherwise the differences were not significant when they
were obtained from the same data set. CONCLUSION: eDKI might be useful for
assessing DKI in clinical settings. KEY POINTS: * A method to practically
estimate axial/radial DKI from limited data was developed. * The high robustness
of the proposed method can greatly improve map images. * The accuracy of the
proposed method was high. * Axial/radial K maps can be calculated from limited
diffusion-encoding directions. * The proposed method might be useful for
assessing DKI in clinical settings.
PMID- 26443603
TI - Quantitative 3D analysis of bone in hip osteoarthritis using clinical computed
tomography.
AB - OBJECTIVE: To assess the relationship between proximal femoral cortical bone
thickness and radiological hip osteoarthritis using quantitative 3D analysis of
clinical computed tomography (CT) data. METHODS: Image analysis was performed on
clinical CT imaging data from 203 female volunteers with a technique called
cortical bone mapping (CBM). Colour thickness maps were created for each proximal
femur. Statistical parametric mapping was performed to identify statistically
significant differences in cortical bone thickness that corresponded with the
severity of radiological hip osteoarthritis. Kellgren and Lawrence (K&L) grade,
minimum joint space width (JSW) and a novel CT-based osteophyte score were also
blindly assessed from the CT data. RESULTS: For each increase in K&L grade,
cortical thickness increased by up to 25 % in distinct areas of the superolateral
femoral head-neck junction and superior subchondral bone plate. For increasing
severity of CT osteophytes, the increase in cortical thickness was more
circumferential, involving a wider portion of the head-neck junction, with up to
a 7 % increase in cortical thickness per increment in score. Results were not
significant for minimum JSW. CONCLUSIONS: These findings indicate that
quantitative 3D analysis of the proximal femur can identify changes in cortical
bone thickness relevant to structural hip osteoarthritis. KEY POINTS: * CT is
being increasingly used to assess bony involvement in osteoarthritis * CBM
provides accurate and reliable quantitative analysis of cortical bone thickness *
Cortical bone is thicker at the superior femoral head-neck with worse
osteoarthritis * Regions of increased thickness co-locate with impingement and
osteophyte formation * Quantitative 3D bone analysis could enable clinical
disease prediction and therapy development.
PMID- 26443604
TI - Is there a systematic bias of apparent diffusion coefficient (ADC) measurements
of the breast if measured on different workstations? An inter- and intra-reader
agreement study.
AB - OBJECTIVES: To evaluate the influence of post-processing systems, intra- and
inter-reader agreement on the variability of apparent diffusion coefficient (ADC)
measurements in breast lesions. METHODS: Forty-one patients with 41 biopsy-proven
breast lesions gave their informed consent and were included in this prospective
IRB-approved study. Magnetic resonance imaging (MRI) examinations were performed
at 1.5 T using an EPI-DWI sequence, with b-values of 0 and 1000 s/mm(2). Two
radiologists (R1, R2) reviewed the images in separate sessions and measured the
ADC for lesion, using MRI-workstation (S-WS), PACS-workstation (P-WS) and a
commercial DICOM viewer (O-SW). Agreement was evaluated using the intraclass
correlation coefficient (ICC), Bland-Altman plots and coefficient of variation
(CV). RESULTS: Thirty-one malignant, two high-risk and eight benign mass-like
lesions were analysed. Intra-reader agreement was almost perfect (ICC-R1 = 0.974;
ICC-R2 = 0.990) while inter-reader agreement was substantial (ICC from 0.615 to
0.682). Bland-Altman plots revealed a significant bias in ADC values measured
between O-SW and S-WS (P = 0.025), no further systematic differences were
identified. CV varied from 6.8 % to 7.9 %. CONCLUSION: Post-processing systems
may have a significant, although minor, impact on ADC measurements in breast
lesions. While intra-reader agreement is high, the main source of ADC variability
seems to be caused by inter-reader variation. KEY POINTS: * ADC provides
quantitative information on breast lesions independent from the system used. *
ADC measurement using different workstations and software systems is generally
reliable. * Systematic, but minor, differences may occur between different post
processing systems. * Inter-reader agreement of ADC measurements exceeded intra
reader agreement.
PMID- 26443605
TI - Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in
Denmark.
AB - STUDY QUESTION: What are the results of transplanting cryopreserved ovarian
tissue? SUMMARY ANSWER: The transplanted ovarian tissue can last up to 10 years,
with no relapses following the 53 transplantations, and the chance of a
successful pregnancy is currently around one in three for those with a pregnancy
wish. WHAT IS KNOWN ALREADY: Cryopreservation of ovarian tissue is now gaining
ground as a valid method for fertility preservation. More than 36 children
worldwide have now been born following this procedure. STUDY DESIGN, SIZE,
DURATION: This is a retrospective cohort study of 41 women who had thawed ovarian
tissue transplanted 53 times over a period of 10 years, including 1 patient who
was lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 41 Danish
women, who had in total 53 transplantations, were followed for ovarian function
and fertility outcome. Safety was assessed by monitoring relapse in cancer
survivors. MAIN RESULTS, AND THE ROLE OF CHANCE: Among 32 women with a pregnancy
wish, 10 (31%) had a child/children (14 children in total); this included 1 woman
with a third trimester on-going pregnancy. In addition, two legal abortions and
one second trimester miscarriage occurred. A total of 24 clinical pregnancies
were established in the 32 women with a pregnancy-wish. The tissue remained
functional for close to 10 years in some cases and lasted only a short period in
others. Three relapses occurred but were unlikely to be due to the transplanted
tissue. LIMITATIONS, REASONS FOR CAUTION: Self-report through questionnaires with
only in-one hospital formalised follow-up of transplanted patients could result
in unreported miscarriages. The longevity of the tissue may vary by few months
compared with those reported because some patients simply could not remember the
date when the tissue became non-functional. WIDER IMPLICATIONS OF THE FINDINGS:
Cryopreservation of ovarian tissue is likely to become integrated into the
treatment of young women, with cancer, who run a risk of losing their fertility.
The full functional lifespan of grafts is still being evaluated, because many of
the transplanted women have continued to maintain ovarian activity. Some of our
first cases have had tissue functioning for ~ 10 years.
PMID- 26443606
TI - David Oliver: Why shouldn't hospitals challenge inspections?
PMID- 26443607
TI - Genetic variants in ANCA-associated vasculitis: a meta-analysis.
AB - BACKGROUND: Genetic factors may influence the pathogenic pathways leading to
antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We
performed a meta-analysis to determine the genetic variants most likely
associated with AAV and investigated whether diagnostic and serological subtypes
within AAV have distinct genetic backgrounds. METHODS: Studies investigating the
association between genetic variants and AAV in humans were searched in PubMed,
EMBASE and Web of Science. All variants investigated in at least two studies were
selected. Subsequently, all studies assessing these variants were included in
this meta-analysis. Additionally, data on these variants from the largest genome
wide association studies in AAV were included to increase the validity of this
meta-analysis. RESULTS: The literature search yielded 5180 articles. 62 articles
investigating 140 genetic variants were included, 33 of which were associated
with AAV in a meta-analysis. These genetic variants were in or near the following
genes: CD226, CTLA-4, FCGR2A, HLA-B, HLA-DP, HLA-DQ, HLA-DR, HSD17B8, IRF5,
PTPN22, RING1/RXRB, RXRB, STAT4, SERPINA1 and TLR9. Moreover, we identified
genetic distinctions between granulomatosis with polyangiitis and microscopic
polyangiitis and between proteinase 3 ANCA vasculitis and myeloperoxidase ANCA
vasculitis. In 76% of the genetic variants, subdivision based on ANCA serotype
resulted in higher ORs than subdivision based on clinical diagnosis. CONCLUSIONS:
This meta-analysis identified 33 genetic variants associated with AAV, supporting
a role for alpha-1-antitrypsin, the major histocompatibility complex system, and
several distinct inflammatory processes in AAV pathogenesis. Our results indicate
that subdivision of AAV based on ANCA serotype has a stronger genetic basis than
subdivision based on clinical diagnosis.
PMID- 26443608
TI - Anticarbamylated protein antibodies are associated with long-term disability and
increased disease activity in patients with early inflammatory arthritis: results
from the Norfolk Arthritis Register.
AB - OBJECTIVES: Anticarbamylated protein (anti-CarP) antibodies are a novel family of
autoantibodies recently identified in patients with inflammatory arthritis. The
aim of this study was to investigate their association with long-term outcomes of
disability and disease activity over 20 years' follow-up in a cohort of patients
with inflammatory polyarthritis (IP). METHODS: Norfolk Arthritis Register
recruited adults with recent-onset swelling of >=2 joints for >=4 weeks from 1990
to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease
activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor
(RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were
measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20
years. Generalised estimating equations were used to test the association between
anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for
age, gender, smoking status, year of inclusion and ACPA status. Analyses were
repeated in subgroups stratified by ACPA status. The relative association of RF,
ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a
random effects model. RESULTS: 1995 patients were included; 1310 (66%) were
female. Anti-CarP antibodies were significantly associated with more disability
and higher disease activity, HAQ multivariate beta-coefficient (95% CI) 0.12
(0.02 to 0.21), and these associations remained significant in the ACPA-negative
subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be
additive in the random effects model. CONCLUSIONS: Anti-CarP antibodies are
associated with increased disability and higher disease activity in patients with
IP. Our results suggest that measurement of anti-CarP antibodies may be useful in
identifying ACPA-negative patients with worse long-term outcomes. Further, anti
CarP antibody status provided additional information about RF and ACPA.
PMID- 26443609
TI - Immunogenicity, drug trough levels and therapeutic response in patients with
rheumatoid arthritis or ankylosing spondylitis after 24-week golimumab treatment.
PMID- 26443610
TI - Cardiac Arrest in Pregnancy: A Scientific Statement From the American Heart
Association.
AB - This is the first scientific statement from the American Heart Association on
maternal resuscitation. This document will provide readers with up-to-date and
comprehensive information, guidelines, and recommendations for all aspects of
maternal resuscitation. Maternal resuscitation is an acute event that involves
many subspecialties and allied health providers; this document will be relevant
to all healthcare providers who are involved in resuscitation and specifically
maternal resuscitation.
PMID- 26443612
TI - Yeast: a microbe with macro-implications to antimicrobial drug discovery.
AB - Paramount to any rational discovery of new antibiotics displaying novel
mechanisms of action is a deep knowledge of the genetic basis of microbial
growth, division and virulence. The bakers' yeast,Saccharomyces cerevisiae,
illustrates the highest understanding of the genetic underpinnings of microbial
life, and from this framework, a systems biology paradigm has evolved, begging to
be emulated in antibacterial discovery. Here, we review landmark events in the
history of yeast genomics that provide this new foundation for antibacterial drug
discovery.
PMID- 26443611
TI - Influence of Sex on Long-Term Outcomes After Implantation of Bare-Metal Stent: A
Multicenter Report From the Coronary Revascularization Demonstrating Outcome
Study-Kyoto (CREDO-Kyoto) Registry Cohort-1.
AB - BACKGROUND: Female sex was reported to be associated with lower risk for midterm
restenosis and repeat revascularization after bare-metal stent implantation.
However, the influence of sex on very long-term outcomes after bare-metal stent
implantation has not been yet reported. METHODS AND RESULTS: Among the 9877
patients in the multicenter Coronary Revascularization Demonstrating Outcome
study in Kyoto (CREDO-Kyoto) registry cohort-1, bare-metal stent implantation was
performed in 5313 patients (men, n=3742 and women, n=1571). Follow-up was
completed in 4515 patients (85.0%) at 10 years (duration, 10.3 +/- 3.1 [0.0-14.1]
years). The cumulative incidence of target-lesion revascularization (TLR) was 27%
at 1 year and 34% at 10 years (0.8%/y beyond 1 year). Non-target-lesion
revascularization (non-TLR) was the dominant coronary revascularization beyond 1
year (13% at 1 year and 31% at 10 years [2.0%/y beyond 1 year]). Cumulative
incidence of stent thrombosis was low (1.2% at 1 year and 1.9% at 10 years).
Women were older and had greater prevalence of cardiovascular risk factors than
men. The cumulative 10-year incidences of and adjusted risk for TLR were
significantly higher in men than in women (36% versus 30%, P<0.001; adjusted
hazard ratio, 1.29; 95% confidence interval, 1.15-1.46; P<0.001). The higher risk
of men relative to women for TLR was consistent regardless of age (<75 years and
>= 75 years). Men in comparison with women were also associated with
significantly higher adjusted risks for all-cause death, myocardial infarction,
stroke, coronary artery bypass grafting, TLR, and non-TLR. CONCLUSIONS: TLR and
stent thrombosis continued to occur without attenuation up to 10 years after bare
metal stent implantation. Men in comparison with women were associated with
higher adjusted 10-year risks for all-cause death, myocardial infarction, stroke,
coronary artery bypass grafting, TLR, and non-TLR.
PMID- 26443613
TI - Quality control, imputation and analysis of genome-wide genotyping data from the
Illumina HumanCoreExome microarray.
AB - The decreasing cost of performing genome-wide association studies has made
genomics widely accessible. However, there is a paucity of guidance for best
practice in conducting such analyses. For the results of a study to be valid and
replicable, multiple biases must be addressed in the course of data preparation
and analysis. In addition, standardizing methods across small, independent
studies would increase comparability and the potential for effective meta
analysis. This article provides a discussion of important aspects of quality
control, imputation and analysis of genome-wide data from a low-coverage
microarray, as well as a straight-forward guide to performing a genome-wide
association study. A detailed protocol is provided online, with example scripts
available at https://github.com/JoniColeman/gwas_scripts.
PMID- 26443614
TI - A Comparison of Base-calling Algorithms for Illumina Sequencing Technology.
AB - Recent advances in next-generation sequencing technology have yielded increasing
cost-effectiveness and higher throughput produced per run, in turn, greatly
influencing the analysis of DNA sequences. Among the various sequencing
technologies, Illumina is by far the most widely used platform. However, the
Illumina sequencing platform suffers from several imperfections that can be
attributed to the chemical processes inherent to the sequencing-by-synthesis
technology. With the enormous amounts of reads produced, statistical
methodologies and computationally efficient algorithms are required to improve
the accuracy and speed of base-calling. Over the past few years, several papers
have proposed methods to model the various imperfections, giving rise to accurate
and/or efficient base-calling algorithms. In this article, we provide a
comprehensive comparison of the performance of recently developed base-callers
and we present a general statistical model that unifies a large majority of these
base-callers.
PMID- 26443616
TI - Nobel awarded to discoverers of ivermectin and artemisinin.
PMID- 26443615
TI - MST2-RASSF protein-protein interactions through SARAH domains.
AB - The detailed, atomistic-level understanding of molecular signaling along the
tumor-suppressive Hippo signaling pathway that controls tissue homeostasis by
balancing cell proliferation and death through apoptosis is a promising avenue
for the discovery of novel anticancer drug targets. The activation of kinases
such as Mammalian STE20-Like Protein Kinases 1 and 2 (MST1 and MST2)-modulated
through both homo- and heterodimerization (e.g. interactions with Ras association
domain family, RASSF, enzymes)-is a key upstream event in this pathway and
remains poorly understood. On the other hand, RASSFs (such as RASSF1A or RASSF5)
act as important apoptosis activators and tumor suppressors, although their exact
regulatory roles are also unclear. We present recent molecular studies of
signaling along the Ras-RASSF-MST pathway, which controls growth and apoptosis in
eukaryotic cells, including a variety of modern molecular modeling and simulation
techniques. Using recently available structural information, we discuss the
complex regulatory scenario according to which RASSFs perform dual signaling
functions, either preventing or promoting MST2 activation, and thus control cell
apoptosis. Here, we focus on recent studies highlighting the special role being
played by the specific interactions between the helical Salvador/RASSF/Hippo
(SARAH) domains of MST2 and RASSF1a or RASSF5 enzymes. These studies are crucial
for integrating atomistic-level mechanistic information about the structures and
conformational dynamics of interacting proteins, with information available on
their system-level functions in cellular signaling.
PMID- 26443617
TI - Junior doctors' dispute goes beyond pay, Tory MP says.
PMID- 26443618
TI - Trade pact disappoints biotechnology companies and campaigners for better access
to drugs.
PMID- 26443619
TI - Longitudinal study of very low birth weight infants until 9years of age;
attention deficit hyperactivity and autistic features are correlated with their
cognitive functions.
AB - BACKGROUND: Increasing attention has been given to neuro-developmental problems
of very low birth weight infants (VLBWIs) at school age. However, it remains
unknown whether their neuro-cognitive function and psychiatric symptoms are
mutually associated. AIM: The aim of this study was to investigate the
characteristics of neuro-cognitive functions in VLBWIs and their relationship
with psychiatric symptoms. METHODS: A total of 160 VLBWIs who were born at our
institute between 2001 and 2005 were recruited consecutively and followed up
until nine years of age. The developmental profiles were obtained from 77
children (45 males and 32 females) at six to nine years of age using the ADHD
Rating Scale-Fourth edition (ADHD-RS), Autism Screening Questionnaire-Japanese
version (ASQ-J) and the Wechsler Intelligence Scale for Children-Third edition
(WISC-III). RESULTS: The full-scale intelligence quotient did not significantly
differ between the male and female VLBWIs (median: 91 vs. 99, p=0.17). The males
had higher total scores (median: 13 vs. 4, p<0.01) and higher scores on the
subscales of Inattention (8 vs. 2, p<0.01) and Hyperactivity-Impulsivity (5 vs.
1, p<0.01) of the ADHD-RS compared with the females. The Verbal Comprehension
Index (VCI) of the WISC-III was inversely correlated with the total scores of the
ASQ-J for all VLBWIs (n=77, rc: -0.32, 95% CI: -0.19 to -0.01, p=0.04). We also
observed that the Freedom from Distractibility Index (FDI) of the WISC-III was
significantly correlated with the Inattentive scores of the ADHD-RS (n=45, rc:
0.18, 95% CI: -0.35 to -0.02, p=0.03) in male, but not female VLBWIs.
CONCLUSIONS: We herein report that the VCI and FDI of the WISC-III were
correlated with the autism spectrum disorder and attention deficit hyperactivity
disorder symptoms, respectively, in male VLBWIs.
PMID- 26443620
TI - Long-term outcome of patients with AL amyloidosis treated with high-dose
melphalan and stem cell transplantation: 20-year experience.
PMID- 26443621
TI - slan-defined subsets of CD16-positive monocytes: impact of granulomatous
inflammation and M-CSF receptor mutation.
AB - Human monocytes are subdivided into classical, intermediate, and nonclassical
subsets, but there is no unequivocal strategy to dissect the latter 2 cell types.
We show herein that the cell surface marker 6-sulfo LacNAc (slan) can define slan
positive CD14(+)CD16(++) nonclassical monocytes and slan-negative CD14(++)CD16(+)
intermediate monocytes. Gene expression profiling confirms that slan-negative
intermediate monocytes show highest expression levels of major histocompatibility
complex class II genes, whereas a differential ubiquitin signature is a novel
feature of the slan approach. In unsupervised hierarchical clustering, the slan
positive nonclassical monocytes cluster with monocytes and are clearly distinct
from CD1c(+) dendritic cells. In clinical studies, we show a selective increase
of the slan-negative intermediate monocytes to >100 cells per microliter in
patients with sarcoidosis and a fivefold depletion of the slan-positive monocytes
in patients with hereditary diffuse leukoencephalopathy with axonal spheroids
(HDLS), which is caused by macrophage colony-stimulating factor (M-CSF) receptor
mutations. These data demonstrate that the slan-based definition of CD16-positive
monocyte subsets is informative in molecular studies and in clinical settings.
PMID- 26443622
TI - Intravenous immune globulin and thromboembolic adverse events in patients with
hematologic malignancy.
AB - In patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia
(CLL) or multiple myeloma (MM), intravenous immune globulin (IVIg) may be
administered to reduce the risk of infection. Since 2013, IVIg products have
carried a boxed safety warning about the risk of thromboembolic events (TEEs),
with TEEs reported in 0.5% to 15% of patients treated with IVIg. In this
retrospective cohort study of older patients with CLL or MM identified from the
Surveillance, Epidemiology, and End Results-Medicare Linked Database, we assessed
rates of clinically serious TEEs in 2724 new users of IVIg and a propensity
matched comparison group of 8035 nonusers. For the primary end point, arterial
TEE, we observed a transient increased risk of TEE during the day of an IVIg
infusion and the day afterward (hazard ration = 3.40; 95% confidence interval
[CI]: 1.25, 9.25); this risk declined over the remainder of the 30-day treatment
cycle. When considered in terms of absolute risk averaged over a 1-year treatment
period, the increase in risk attributable to IVIg was estimated to be 0.7% (95%
CI: -0.2%, 2.0%) compared with a baseline risk of 1.8% for the arterial TEE end
point. A statistically nonsignificant risk increase of 0.3% (95% CI: -0.4%, 1.5%)
compared with a baseline risk of 1.1% was observed for the venous TEE end point.
Further research is needed to establish the generalizability of these results to
patients receiving higher doses of IVIg for other indications.
PMID- 26443623
TI - NADPH oxidase controls neutrophilic response to sterile inflammation in mice by
regulating the IL-1alpha/G-CSF axis.
AB - The leukocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
generates reactive oxygen species essential in microbial killing and regulation
of inflammation. Inactivating mutations in this enzyme lead to chronic
granulomatous disease (CGD), associated with increased susceptibility to both
pyogenic infections and to inflammatory disorders. The role of the NADPH oxidase
in regulating inflammation driven by nonmicrobial stimuli is poorly understood.
Here, we show that NADPH oxidase deficiency enhances the early local release of
interleukin-1alpha (IL-1alpha) in response to damaged cells, promoting an
excessive granulocyte colony-stimulating factor (G-CSF)-regulated neutrophilic
response and prolonged inflammation. In peritoneal inflammation elicited by
tissue injury, X-linked Cybb-null (X-CGD) mice exhibited increased release of IL
1alpha and IL-1 receptor -mediated G-CSF production. In turn, higher levels of
systemic G-CSF increased peripheral neutrophilia, which amplified neutrophilic
peritoneal inflammation in X-CGD mice. Dampening early neutrophil recruitment by
neutralization of IL-1alpha, G-CSF, or neutrophil depletion itself promoted
resolution of otherwise prolonged inflammation in X-CGD. IL-1beta played little
role. Thus, we identified an excessive IL-1alpha/G-CSF response as a major driver
of enhanced sterile inflammation in CGD in the response to damaged cells. More
broadly, these results provide new insights into the regulation of sterile
inflammation, and identify the NADPH oxidase in regulating the amplitude of the
early neutrophilic response.
PMID- 26443625
TI - Effectiveness of glucose-methanol extender for cryopreservation of Huso huso
spermatozoa.
AB - The present approach was designed to evaluate the methanol-glucose extender
effects on sperm cryopreservation in beluga sturgeon, Huso huso. Sperm quality
was examined by measuring post-thaw sperm motility and fertilizing rate at
hatching stage. We first tested the effect of glucose concentration (0, 0.10,
0.15, 0.20 and 0.30M) in a methanol extender on post-thaw sperm motility. The
optimal cryopreservation conditions were found to be 0.2M glucose in the
extender. Then, motility and fertilization rates of sperm cryopreserved with 0.2M
glucose and 10% methanol (GM) were compared to Tris-sucrose-KCl in 10% methanol
extender (TSKM). Additionally, sperm motility and fertilizing ability in relation
to 15 and 30min equilibration in GM extender before and after cryopreservation
were measured. Higher post-thaw sperm motility duration and percentage as well as
fertilization rate were obtained with the GM extender when compared to TSKM
extender. Equilibration of sperm in extender did not affect the motility quality
of either fresh-diluted or frozen/thawed sperm, while fertilization rate showed a
significant decline alone after 30min of post-thaw storage. Our results indicated
that the use of a simple extender consisting of 0.2M glucose in 10% methanol can
be an alternative cryopreservation method to those previously described for
sturgeons.
PMID- 26443624
TI - Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute
lymphoblastic leukemias.
AB - The development of the dual Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib for
the treatment of myeloproliferative neoplasms (MPNs) has led to studies of
ruxolitinib in other clinical contexts, including JAK-mutated acute lymphoblastic
leukemia (ALL). However, the limited ability of JAK inhibition to induce
molecular or clinicopathological responses in MPNs suggests a need for
development of better therapies for JAK kinase-dependent malignancies. Here, we
demonstrate that heat shock protein 90 (HSP90) inhibition using a purine-scaffold
HSP90 inhibitor in early clinical development is an effective therapeutic
approach in JAK-dependent ALL and can overcome persistence to JAK-inhibitor
therapy in ALL cells.
PMID- 26443626
TI - Multidimensional staging system for pediatric acquired cholesteatoma: A 30-year
verification data.
AB - OBJECTIVE: This article presents a points-based prognostic prediction model for
pediatric acquired cholesteatoma, incorporating the multidimensional factors that
contribute to surgical failure. METHODS: This study included 132 ears with
acquired cholesteatoma from 128 children (<=18 years) identified between 1982 and
2012. Each case was scored for the extent of the cholesteatoma, history of
grommet insertion, age of the patient, ossicular destruction, and otorrhea. The
patients were classified as stage I, II, or III. We compared differences between
stages regarding the cumulative rates of recidivism and linear trends in these
rates. RESULTS: Among stage I cases, the rate of cumulative recidivism was 0%;
however, among stage 2 cases, this increased with time, eventually leveling off
at 15.7% after 18 years of follow-up. The same was observed among stage III
cases, which leveled off at 34.1% after 17 years of follow-up. In the second half
of the cohort and the entire cohort, differences in the cumulative recidivism
curves reached statistical significance, as did the linear trends (all p<0.05).
CONCLUSIONS: Our findings demonstrate the efficacy of the proposed
multidimensional staging system in linking the severity of cholesteatoma to
outcomes, thereby enabling the stratification of patients according to prognosis
in order to identify children at risk of recidivism.
PMID- 26443627
TI - Older patients with HIV should be offered cancer screening, study recommends.
PMID- 26443628
TI - Misdiagnosis of gastroesophageal reflux disease as epileptic seizures in
children.
AB - BACKGROUND: Gastroesophageal reflux disease (GERD) can mimic epileptic seizure,
and may be misdiagnosed as epilepsy. On the other hand, GERD can be more commonly
seen in children with neurological disorders such as cerebral palsy (CP); this co
incidence may complicate the management of patients by mimicking refractory
seizures. OBJECTIVE: The purpose of our study was to evaluate the clinical
features, definite diagnoses and treatment approaches of the patients with
clinically suspected GERD who were referred to the division of pediatric
neurology with a suspected diagnosis of epileptic seizure. We also aimed to
investigate the occurrence of GERD in children with epilepsy and/or CP. METHODS:
Fifty-seven children who had a final diagnosis of GERD but were initially
suspected of having epileptic seizures were assessed prospectively. RESULTS: All
patients were assigned to 3 groups according to definite diagnoses as follows:
patients with only GERD who were misdiagnosed as having epileptic seizure (group
1: n=16; 28.1%), those with comorbidity of epilepsy and GERD (group 2: n=21;
36.8%), and those with the coexistence of GERD with epilepsy and CP (group 3:
n=20; 35.1%). Five patients (8.8%) did not respond to anti-reflux treatment and
laparoscopic reflux surgery was performed. The positive effect of GERD therapy on
paroxysmal nonepileptic events was observed in 51/57 (89.5%) patients.
CONCLUSIONS: GERD is one of the important causes of paroxysmal nonepileptic
events. In addition, GERD must be kept in mind at the initial diagnosis and also
in the long-term management of patients with neurological disorders such as
epilepsy and CP.
PMID- 26443629
TI - Novel missense mutation in CLN8 in late infantile neuronal ceroid lipofuscinosis:
The first report of a CLN8 mutation in Japan.
AB - Neuronal ceroid lipofuscinoses (NCLs) are clinically and genetically
heterogeneous neurodegenerative lysosomal diseases. Fourteen distinct NCL
subtypes (CLN1-CLN14) are known, and they are caused by mutations in different
genes. CLN8 was first identified in Finnish patients, and the phenotype was
subsequently found in Turkish, Italian, and Pakistani patients. We report a 6
year-old Japanese boy with NCL with a novel missense mutation in CLN8. At the age
of 3years, he manifested frequent drop seizures, and then progressively developed
motor difficulties with an ataxic gait, myoclonus, left conjugate deviation, and
rotational nystagmus. At age 5, he developed profound visual difficulty and
dysphagia, and he has now lost his mobility. A bone marrow examination at age 5
showed sea-blue histiocytes. An electroretinogram was non-recordable. No giant
somatosensory evoked potentials were found. Brain magnetic resonance imaging
revealed bilateral diffuse hyperintensities in the white matter around the
lateral ventricles and cerebellar and pontine atrophy on T2-weighted images. In a
lysosomal enzyme study, the palmitoyl-protein-thioesterase and pepinase activity
was within normal limits. Whole-exome sequencing revealed a homozygous CLN8
mutation: c.620T>G (p.L207R). His parents were both heterozygous for this
mutation. To our knowledge, this is the first report of a CLN8 mutation in late
infantile NCL in Japan.
PMID- 26443630
TI - Spreading the word: non-autonomous effects of apoptosis during development,
regeneration and disease.
AB - Apoptosis, in contrast to other forms of cell death such as necrosis, was
originally regarded as a 'silent' mechanism of cell elimination designed to
degrade the contents of doomed cells. However, during the past decade it has
become clear that apoptotic cells can produce diverse signals that have a
profound impact on neighboring cells and tissues. For example, apoptotic cells
can release factors that influence the proliferation and survival of adjacent
tissues. Apoptosis can also affect tissue movement and morphogenesis by modifying
tissue tension in surrounding cells. As we review here, these findings reveal
unexpected roles for apoptosis in tissue remodeling during development, as well
as in regeneration and cancer.
PMID- 26443632
TI - A developmental framework for induced pluripotency.
AB - During development, cells transition from a pluripotent to a differentiated
state, generating all the different types of cells in the body. Development is
generally considered an irreversible process, meaning that a differentiated cell
is thought to be unable to return to the pluripotent state. However, it is now
possible to reprogram mature cells to pluripotency. It is generally thought that
reprogramming is accomplished by reversing the natural developmental
differentiation process, suggesting that the two mechanisms are closely related.
Therefore, a detailed study of cell reprogramming has the potential to shed light
on unexplained developmental mechanisms and, conversely, a better understanding
of developmental differentiation can help improve cell reprogramming. However,
fundamental differences between reprogramming processes and multi-lineage
specification during early embryonic development have also been uncovered. In
addition, there are multiple routes by which differentiated cells can re-enter
the pluripotent state. In this Review, we discuss the connections and disparities
between differentiation and reprogramming, and assess the degree to which
reprogramming can be considered as a simple reversal of development.
PMID- 26443631
TI - Photoreceptor cell fate specification in vertebrates.
AB - Photoreceptors--the light-sensitive cells in the vertebrate retina--have been
extremely well-characterized with regards to their biochemistry, cell biology and
physiology. They therefore provide an excellent model for exploring the factors
and mechanisms that drive neural progenitors into a differentiated cell fate in
the nervous system. As a result, great progress in understanding the
transcriptional network that controls photoreceptor specification and
differentiation has been made over the last 20 years. This progress has also
enabled the production of photoreceptors from pluripotent stem cells, thereby
aiding the development of regenerative medical approaches to eye disease. In this
Review, we outline the signaling and transcription factors that drive vertebrate
photoreceptor development and discuss how these function together in gene
regulatory networks to control photoreceptor cell fate specification.
PMID- 26443633
TI - Differentiation of human embryonic stem cells into cone photoreceptors through
simultaneous inhibition of BMP, TGFbeta and Wnt signaling.
AB - Cone photoreceptors are required for color discrimination and high-resolution
central vision and are lost in macular degenerations, cone and cone/rod
dystrophies. Cone transplantation could represent a therapeutic solution.
However, an abundant source of human cones remains difficult to obtain. Work
performed in model organisms suggests that anterior neural cell fate is induced
'by default' if BMP, TGFbeta and Wnt activities are blocked, and that
photoreceptor genesis operates through an S-cone default pathway. We report here
that Coco (Dand5), a member of the Cerberus gene family, is expressed in the
developing and adult mouse retina. Upon exposure to recombinant COCO, human
embryonic stem cells (hESCs) differentiated into S-cone photoreceptors, developed
an inner segment-like protrusion, and could degrade cGMP when exposed to light.
Addition of thyroid hormone resulted in a transition from a unique S-cone
population toward a mixed M/S-cone population. When cultured at confluence for a
prolonged period of time, COCO-exposed hESCs spontaneously developed into a
cellular sheet composed of polarized cone photoreceptors. COCO showed dose
dependent and synergistic activity with IGF1 at blocking BMP/TGFbeta/Wnt
signaling, while its cone-inducing activity was blocked in a dose-dependent
manner by exposure to BMP, TGFbeta or Wnt-related proteins. Our work thus
provides a unique platform to produce human cones for developmental, biochemical
and therapeutic studies and supports the hypothesis that photoreceptor
differentiation operates through an S-cone default pathway during human retinal
development.
PMID- 26443634
TI - Regulation of Nematostella neural progenitors by SoxB, Notch and bHLH genes.
AB - Notch signalling, SoxB and Group A bHLH 'proneural' genes are conserved
regulators of the neurogenic program in many bilaterians. However, the ancestry
of their functions and interactions is not well understood. We address this
question in the sea anemone Nematostella vectensis, a representative of the
Cnidaria, the sister clade to the Bilateria. It has previously been found that
the SoxB orthologue NvSoxB(2) is expressed in neural progenitor cells (NPCs) in
Nematostella and promotes the development of both neurons and nematocytes,
whereas Notch signalling has been implicated in the negative regulation of
neurons and the positive regulation of nematocytes. Here, we clarify the role of
Notch by reporting that inhibition of Notch signalling increases the numbers of
both neurons and nematocytes, as well as increasing the number of NvSoxB(2)
expressing cells. This suggests that Notch restricts neurogenesis by limiting the
generation of NPCs. We then characterise NvAth-like (Atonal/Neurogenin family) as
a positive regulator of neurogenesis that is co-expressed with NvSoxB(2) in a
subset of dividing NPCs, while we find that NvAshA (Achaete-scute family) and
NvSoxB(2) are co-expressed in non-dividing cells only. Reciprocal knockdown
experiments reveal a mutual requirement for NvSoxB(2) and NvAth-like in neural
differentiation; however, the primary expression of each gene is independent of
the other. Together, these data demonstrate that Notch signalling and NvSoxB(2)
regulate Nematostella neural progenitors via parallel yet interacting mechanisms;
with different aspects of these interactions being shared with Drosophila and/or
vertebrate neurogenesis.
PMID- 26443635
TI - The small leucine-rich repeat secreted protein Asporin induces eyes in Xenopus
embryos through the IGF signalling pathway.
AB - Small leucine-rich repeat proteoglycan (SLRP) family proteins play important
roles in a number of biological events. Here, we demonstrate that the SLRP family
member Asporin (ASPN) plays a crucial role in the early stages of eye development
in Xenopus embryos. During embryogenesis, ASPN is broadly expressed in the
neuroectoderm of the embryo. Overexpression of ASPN causes the induction of
ectopic eyes. By contrast, blocking ASPN function with a morpholino
oligonucleotide (ASPN-MO) inhibits eye formation, indicating that ASPN is an
essential factor for eye development. Detailed molecular analyses revealed that
ASPN interacts with insulin growth factor receptor (IGFR) and is essential for
activating the IGF receptor-mediated intracellular signalling pathway. Moreover,
ASPN perturbed the Wnt, BMP and Activin signalling pathways, suggesting that ASPN
thereby creates a favourable environment in which the IGF signal can dominate.
ASPN is thus a novel secreted molecule essential for eye induction through the
coordination of multiple signalling pathways.
PMID- 26443636
TI - Wnt/beta-catenin signaling modulates corneal epithelium stratification via
inhibition of Bmp4 during mouse development.
AB - The development of organs with an epithelial parenchyma relies on reciprocal
mesenchymal-epithelial communication. Mouse corneal epithelium stratification is
the consequence of a coordinated developmental process based on mesenchymal
epithelial interactions. The molecular mechanism underlying these interactions
remains unclear. The Wnt/beta-catenin signaling pathway is involved in
fundamental aspects of development through the regulation of various growth
factors. Here, we show that conditional ablation of either beta-catenin
(Ctnnb1(cKO)) or co-receptors Lrp5/6 (Lrp5/6(cKO)) in corneal stromal cells
results in precocious stratification of the corneal epithelium. By contrast,
ectopic expression of a murine Ctnnb1 gain-of-function mutant (Ctnnb1(cGOF))
retards corneal epithelium stratification. We also discovered that Bmp4 is
upregulated in the absence of beta-catenin in keratocytes, which further triggers
ERK1/2 (Mapk3/1) and Smad1/5 phosphorylation and enhances transcription factor
p63 (Trp63) expression in mouse corneal basal epithelial cells and in a human
corneal epithelial cell line (HTCE). Interestingly, mouse neonates given a
subconjunctival BMP4 injection displayed a phenotype resembling that of
Ctnnb1(cKO). Conditional ablation of Bmp4 eradicates the phenotype produced in
Ctnnb1(cKO) mice. Furthermore, ChIP and promoter-luciferase assays show that beta
catenin binds to and suppresses Bmp4 promoter activity. These data support the
concept that cross-talk between the Wnt/beta-catenin/Bmp4 axis (in the stromal
mesenchyme) and Bmp4/p63 signaling (in the epithelium) plays a pivotal role in
epithelial stratification during corneal morphogenesis.
PMID- 26443637
TI - Cell type-specific translational repression of Cyclin B during meiosis in males.
AB - The unique cell cycle dynamics of meiosis are controlled by layers of regulation
imposed on core mitotic cell cycle machinery components by the program of germ
cell development. Although the mechanisms that regulate Cdk1/Cyclin B activity in
meiosis in oocytes have been well studied, little is known about the trans-acting
factors responsible for developmental control of these factors in male
gametogenesis. During meiotic prophase in Drosophila males, transcript for the
core cell cycle protein Cyclin B1 (CycB) is expressed in spermatocytes, but the
protein does not accumulate in spermatocytes until just before the meiotic
divisions. Here, we show that two interacting proteins, Rbp4 and Fest, expressed
at the onset of spermatocyte differentiation under control of the developmental
program of male gametogenesis, function to direct cell type- and stage-specific
repression of translation of the core G2/M cell cycle component cycB during the
specialized cell cycle of male meiosis. Binding of Fest to Rbp4 requires a 31
amino acid region within Rbp4. Rbp4 and Fest are required for translational
repression of cycB in immature spermatocytes, with Rbp4 binding sequences in a
cell type-specific shortened form of the cycB 3' UTR. Finally, we show that Fest
is required for proper execution of meiosis I.
PMID- 26443639
TI - Dynamic measurement of patello-femoral joint alignment using weight-bearing
magnetic resonance imaging (WB-MRI).
AB - OBJECTIVE: Aim of our work was to compare standard and weight-bearing WB-MRI to
define their contribution in unmasking patello-femoral (PF) maltracking and to
define what measurement of patellar alignment is the most reliable. METHODS: We
prospectively collected 95 non consecutive patients, clinically divided into 2
groups: group A (the control group), including 20 patients (negative for patellar
maltracking), and group B including 75 patients (positive for patellar
maltracking). The patients underwent a dedicated 0.25 T MRI, in supine and WB
position, with knee flexion of 12-15 degrees . The following measurements were
performed: Insall-Salvati index (IS), lateral patellar displacement (LPD),
lateral patello-femoral angle (LPA) and lateral patellar tilt (LPT). Quantitative
and qualitative statistical analyses were performed to compare the results
obtained before and after WB-MRI. Measurements were subsequently performed on
both groups. RESULTS: Group A patients showed no statistically significant
variations at all measurements both on standard and WB-MRI. On the basis of
measurements made on standard MRI, group B patients were divided into group B1
(23 patients) (negative or positive at 1 measurement) and group B2 (52 patients)
(positive at 2 or more measurements). After WB-MRI, group B1 patients were
divided into group B1a (6 patients), in case they remained positive at 0/1
measurement, and group B1b (17 patients), in case they became positive at 2 or
more measurements. All group B2 patients confirmed to be positive at 2 or more
measurements at WB-MRI. Quantitative statistical analysis showed that LPT and LPA
were the most reproducible and clinically useful measurements. Qualitative
statistical analysis performed on standard and WB-MRI demonstrated that LPT was
the best predictive measurement. CONCLUSIONS: This study demonstrates both the
high diagnostic value of WB-MRI in unmasking PF-maltracking and the best
predictive value of LPT measurement.
PMID- 26443640
TI - Expiratory air trapping during asthma exacerbation: Relationships with clinical
indices and proximal airway morphology.
AB - OBJECTIVES: To semi-quantitatively assess expiratory air trapping (AT(exp)) and
structural changes in the proximal airways in asthma during asthma exacerbation
(AE) and to explore the relationships among AT(exp), clinical indices, and
proximal airway changes. METHODS: Paired inspiratory-dynamic forced expiratory CT
scans of 36 asthmatics (30 women, 6 men; mean age, 49.2+/-18.9 years) performed
during AE were retrospectively reviewed for the total AT(exp) score (summed
scores [extent grading (0-4)*pattern grading (1-4)] of the twelve lung zones),
morphologic parameters and expiratory bronchial collapse (BC(exp)) of the
proximal airways. The relationships of the score with clinical indices and
proximal airway morphology (normalized by body surface area [BSA]) were analyzed.
A p value of <0.05 was considered statistically significant. RESULTS: The mean
total AT(exp) score was 110.1+/-43.4 (range, 8-166). It was higher in the lower
zones and in patients older than 60 years, having BMI of <27.5 kg/m(2), and peak
expiratory flow rate (PEFR) of <60% predicted. Correlation existed between the
score and age (r=0.331), BMI (r=-0.375), BSA (r=-0.442), % predicted PEFR (r=
0.332), right upper lobe apical segmental bronchus (RB1)-wall area (WA)/BSA
(r=0.467), %RB1-WA (r=0.395), and RB1-bronchial wall thickness (BWT)/BSA
(r=0.378). The score showed no correlation with BC(exp) and other morphologic
bronchial parameters. Area under receiver-operating-characteristic curve 0.724
(95% CI) showed that the score of 110 could discriminate patients with PEFR of
<60% predicted from those with PEFR of >=60% predicted. CONCLUSION: During AE,
there was a high prevalence of extensive AT(exp) which was correlated with
patient's age, BMI, BSA, AE severity and RB1 morphology but not correlated with
BC(exp).
PMID- 26443638
TI - Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1
and Nkx6 genes in Xenopus.
AB - V1 interneurons are inhibitory neurons that play an essential role in vertebrate
locomotion. The molecular mechanisms underlying their genesis remain, however,
largely undefined. Here, we show that the transcription factor Prdm12 is
selectively expressed in p1 progenitors of the hindbrain and spinal cord in the
frog embryo, and that a similar restricted expression profile is observed in the
nerve cord of other vertebrates as well as of the cephalochordate amphioxus.
Using frog, chick and mice, we analyzed the regulation of Prdm12 and found that
its expression in the caudal neural tube is dependent on retinoic acid and Pax6,
and that it is restricted to p1 progenitors, due to the repressive action of Dbx1
and Nkx6-1/2 expressed in the adjacent p0 and p2 domains. Functional studies in
the frog, including genome-wide identification of its targets by RNA-seq and ChIP
Seq, reveal that vertebrate Prdm12 proteins act as a general determinant of V1
cell fate, at least in part, by directly repressing Dbx1 and Nkx6 genes. This
probably occurs by recruiting the methyltransferase G9a, an activity that is not
displayed by the amphioxus Prdm12 protein. Together, these findings indicate that
Prdm12 promotes V1 interneurons through cross-repressive interactions with Dbx1
and Nkx6 genes, and suggest that this function might have only been acquired
after the split of the vertebrate and cephalochordate lineages.
PMID- 26443641
TI - Factors Associated with Hospitalization among Emergency Department Patients
Referred for Quick Investigation of Iron-Deficiency Anemia.
AB - BACKGROUND: Although patients with anemia are frequently seen in emergency
departments (EDs), studies on patients presenting there with symptomatic chronic
anemia--usually iron-deficiency anemia (IDA) caused by occult gastrointestinal
bleeding--are lacking. Awareness of predictors of hospitalization could direct
the ED triage to the appropriate diagnostic setting. OBJECTIVE: Based on initial
observations that some patients with IDA were hospitalized after ED referral and
initial evaluation at a quick diagnosis unit (QDU), a new cost-effective
alternative to hospitalization for diagnostic workup, this study aimed to
determine the patient factors associated with hospitalization after the first QDU
visit. METHODS: An 8-year prospective cohort study of patients with IDA referred
from the ED to the QDU of a third-level university hospital was conducted.
Patients with a baseline hemoglobin level of <9 g/dL in the ED, proven iron
deficiency, and no overt bleeding were included. The primary outcome was
hospitalization after the initial QDU assessment. RESULTS: Two hundred eighty
four (7.7%) of 3692 patients were hospitalized. Inter-rater agreement of
appropriateness of admissions was 90.6% (kappa = 0.82). Overall, 90% of study
patients presented to the ED with symptomatic anemia, and 87% were transfused
there. On multivariate analysis, age >= 65 years, living alone, a post
transfusion hemoglobin level of <9 g/dL, higher age-adjusted overall comorbidity,
heart failure, and poor physical health-related quality of life at first QDU
visit independently predicted hospitalization. CONCLUSION: While these predictors
do not necessarily reflect the need for hospitalization, they are easily
evaluated during the initial ED visit and can guide the triage of similar IDA
patients to the suitable setting for timely investigation.
PMID- 26443642
TI - Young Man with Sore Throat, Headache, and Rash.
PMID- 26443643
TI - Septic Pulmonary Emboli Associated with Klebsiella Pneumoniae Epididymitis.
PMID- 26443644
TI - Assessment of Emergency Department Eye Examinations in Patients Presenting with
Mid-Face Injury.
AB - BACKGROUND: One-fifth of patients with severe facial trauma suffer ophthalmic
injury. Currently, patients presenting with mid-face injury to the emergency
department (ED) undergo visual examination and then further assessment by
ophthalmologists and with computed tomography (CT) scanning. The utility of the
initial visual examination in the ED, performed by nonophthalmologists, remains
unclear. OBJECTIVE: We aimed to objectively identify whether a more thorough
initial visual assessment, performed by nonophthalmologists in the ED, was
associated with improved ophthalmic outcomes. METHODS: Patients (n = 100) were
retrospectively recruited from a tertiary craniomaxillofacial center. Visual
examinations performed in the ED were scored objectively and measured against
defined management and prognostic outcomes. RESULTS: There was no significant
difference between more thorough initial visual examination and reduced time to
ophthalmology assessment or reduced visual complications. There was no
correlation between more comprehensive examination and incidence of CT scanning.
CONCLUSIONS: We identified no significant difference between a comprehensive
visual examination performed by nonophthalmologists in the ED, and improved
ophthalmic outcomes. Physicians assessing patients with mid-face trauma in the ED
should rule out eye emergencies, including retrobulbar hemorrhage and penetrating
globe injury, and initiate expeditious CT scan and assessment by specialist
ophthalmologists.
PMID- 26443645
TI - Development of an International Elective in an Emergency Medicine Residency.
AB - BACKGROUND: There is a continued interest in global emergency medicine (EM)
training, research, and clinical program development. There are many
opportunities for "voluntourism" in medicine, but many of these experiences do
not have standard goals and objectives. OBJECTIVE: This article describes a
rotation for EM residents from the United States to have a structured learning
experience focusing on emergency medical settings in the prehospital phase
(something often lacking in U.S. programs). DISCUSSION: The authors discuss the
structure of the training program, including goals, objectives, and core
competencies. First-hand accounts of the training experience are also presented.
CONCLUSIONS: Global training experiences can have clear benefits. Students go to
places to "learn," but can also "teach" at the same time. Setting goals and
objectives helps to assure that students are gaining specific core competencies
as part of the experience. Other global rotations would benefit from having a
defined structure.
PMID- 26443646
TI - The Joys and Pains of Major Medical Journals.
PMID- 26443647
TI - Simultaneous imaging of blood flow dynamics and vascular remodelling during
development.
AB - Normal vascular development requires blood flow. Time-lapse imaging techniques
have revolutionised our understanding of developmental biology, but measuring
changes in blood flow dynamics has met with limited success. Ultrasound
biomicroscopy and optical coherence tomography can concurrently image vascular
structure and blood flow velocity, but these techniques lack the resolution to
accurately calculate fluid forces such as shear stress. This is important because
hemodynamic forces are biologically active and induce changes in the expression
of genes important for vascular development. Regional variations in shear stress,
rather than the overall level, control processes such as vessel enlargement and
regression during vascular remodelling. We present a technique to concurrently
visualise vascular remodelling and blood flow dynamics. We use an avian embryonic
model and inject an endothelial-specific dye and fluorescent microspheres. The
motion of the microspheres is captured with a high-speed camera and the velocity
of the blood flow in and out of the region of interest is quantified by micro
particle image velocitymetry (uPIV). The vessel geometry and flow are used to
numerically solve the flow physics with computational fluid dynamics (CFD). Using
this technique, we can analyse changes in shear stress, pressure drops and blood
flow velocities over a period of 10 to 16 h. We apply this to study the
relationship between shear stress and chronic changes in vessel diameter during
embryonic development, both in normal development and after TGFbeta stimulation.
This technique allows us to study the interaction of biomolecular and
biomechanical signals during vascular remodelling using an in vivo developmental
model.
PMID- 26443648
TI - The Nonspecific Binding of Tyrosine Kinase Inhibitors to Human Liver Microsomes.
AB - Drugs and other chemicals frequently bind nonspecifically to the constituents of
an in vitro incubation mixture, particularly the enzyme source [e.g., human liver
microsomes (HLM)]. Correction for nonspecific binding (NSB) is essential for the
accurate calculation of the kinetic parameters Km, Clint, and Ki. Many tyrosine
kinase inhibitors (TKIs) are lipophilic organic bases that are nonionized at
physiologic pH. Attempts to measure the NSB of several TKIs to HLM by equilibrium
dialysis proved unsuccessful, presumably due to the limited aqueous solubility of
these compounds. Thus, the addition of detergents to equilibrium dialysis samples
was investigated as an approach to measure the NSB of TKIs. The binding of six
validation set nonionized lipophilic bases (felodipine, isradipine, loratidine,
midazolam, nifedipine, and pazopanib) to HLM (0.25 mg/ml) was shown to be
unaffected by the addition of CHAPS (6 mM) to the dialysis medium. This approach
was subsequently applied to measurement of the binding of axitinib, dabrafenib,
erlotinib, gefitinib, ibrutinib, lapatinib, nilotinib, nintedanib, regorafenib,
sorafenib, and trametinib to HLM (0.25 mg/ml). As with the validation set drugs,
attainment of equilibrium was demonstrated in HLM-HLM and buffer-buffer control
dialysis experiments. Values of the fraction unbound to HLM ranged from 0.14
(regorafenib and sorafenib) to 0.93 (nintedanib), and were generally consistent
with the known physicochemical determinants of drug NSB. The extensive NSB of
many TKIs to HLM underscores the importance of correction for TKI binding to HLM
and, presumably, other enzyme sources present in in vitro incubation mixtures.
PMID- 26443649
TI - Musculoskeletal pain and limitations in work ability in Swedish marines: a cross
sectional survey of prevalence and associated factors.
AB - OBJECTIVES: To estimate the prevalence of self-rated musculoskeletal pain and
pain limiting work ability in Swedish Armed Forces (SAF) marines, and to study
factors potentially associated with pain limiting work ability for the most
prevalent pain regions reported. DESIGN: Population-based, cross-sectional
survey. PARTICIPANTS: There were 272 SAF marines from the main marine battalion
in Sweden included in the study. OUTCOMES: Self-assessed musculoskeletal pain and
pain limiting the marines' work ability within a 6-month period, as obtained from
structured questionnaires. The association of individual, health and work-related
factors with musculoskeletal pain limiting work ability was systematically
regressed with multiple logistic models, estimating OR and 95% CI. RESULTS:
Musculoskeletal pain and pain limiting work ability were most common in the back,
at 46% and 20%, and lower extremities at 51% and 29%, respectively. Physical
training <=1 day/week (OR 5.3, 95% CI 1.7 to 16.8); body height <=1.80 m (OR 5.0,
95% CI 1.6 to 15.1) and >=1.86 m (OR 4.4, 95% CI 1.4 to 14.1); computer work 1/4
of the working day (OR 3.2, 95% CI 1.0 to 10.0) and >=1/2 (OR 3.3, 95% CI 1.1 to
10.1) of the working day were independently associated with back pain limiting
work ability. None of the studied variables emerged significantly associated with
such pain for the lower extremities. CONCLUSIONS: Our findings show that
musculoskeletal pain and resultant limitations in work ability are common in SAF
marines. Low frequency of physical training emerged independently associated with
back pain limiting work ability. This suggests that marines performing physical
training 1 day per week or less are suitable candidates for further medical
evaluation and secondary preventive actions. While also associated, body height
and computer work need further exploration as underlying mechanisms for back pain
limiting work ability. Further prospective studies are necessary to clarify the
direction of causality.
PMID- 26443650
TI - Accuracy and readability of cardiovascular entries on Wikipedia: are they
reliable learning resources for medical students?
AB - OBJECTIVE: To evaluate accuracy of content and readability level of English
Wikipedia articles on cardiovascular diseases, using quality and readability
tools. METHODS: Wikipedia was searched on the 6 October 2013 for articles on
cardiovascular diseases. Using a modified DISCERN (DISCERN is an instrument
widely used in assessing online resources), articles were independently scored by
three assessors. The readability was calculated using Flesch-Kincaid Grade Level.
The inter-rater agreement between evaluators was calculated using the Fleiss
kappa scale. RESULTS: This study was based on 47 English Wikipedia entries on
cardiovascular diseases. The DISCERN scores had a median=33 (IQR=6). Four
articles (8.5%) were of good quality (DISCERN score 40-50), 39 (83%) moderate
(DISCERN 30-39) and 4 (8.5%) were poor (DISCERN 10-29). Although the entries
covered the aetiology and the clinical picture, there were deficiencies in the
pathophysiology of diseases, signs and symptoms, diagnostic approaches and
treatment. The number of references varied from 1 to 127 references; 25.9+/-29.4
(mean+/-SD). Several problems were identified in the list of references and
citations made in the articles. The readability of articles was 14.3+/-1.7
(mean+/-SD); consistent with the readability level for college students. In
comparison, Harrison's Principles of Internal Medicine 18th edition had more
tables, less references and no significant difference in number of graphs,
images, illustrations or readability level. The overall agreement between the
evaluators was good (Fleiss kappa 0.718 (95% CI 0.57 to 0.83). CONCLUSIONS: The
Wikipedia entries are not aimed at a medical audience and should not be used as a
substitute to recommended medical resources. Course designers and students should
be aware that Wikipedia entries on cardiovascular diseases lack accuracy,
predominantly due to errors of omission. Further improvement of the Wikipedia
content of cardiovascular entries would be needed before they could be considered
a supplementary resource.
PMID- 26443651
TI - Pregnancy-related venous thrombosis: comparison between spontaneous and ART
conception in an Italian cohort.
AB - OBJECTIVE: To evaluate in an Italian cohort the incidence of venous
thromboembolic events (VTE) in pregnancies after assisted reproductive
technologies (ART). SETTING: Thrombosis and Haemostasis Unit at I.R.C.C.S. 'Casa
Sollievo della Sofferenza', S. Giovanni Rotondo. PARTICIPANTS: A prospective
cohort of 998 women advised to undergo ART was referred by local fertility
clinics from April 2002 to July 2011. Follow-up information was obtained during
the check-up and/or by phone interviews. In a cohort of women who consecutively
gave birth (n=3339) after spontaneous conception in our Institution, information
on the diagnoses of pregnancy-related venous thromboses was obtained by linkage
to a patient administrative register. PRIMARY AND SECONDARY OUTCOME MEASURES: We
calculated the incidence of VTE and superficial venous thrombosis in successful
ART cycles and compared it with that of the general population conceiving
spontaneously. RESULTS: Overall, 684 ART cycles were carried out by 234 women,
who achieved a clinical pregnancy; in case of more than one successful cycle,
only the first pregnancy was considered. Three vein thromboses (two VTE and one
superficial vein thrombosis) were recorded. An antithrombotic prophylaxis with
LMWH alone or combined with low-dose aspirin was prescribed in 23/234 (9.8%)
women. In the reference cohort of 3339 women, a total of 11 vein thromboses were
observed: six VTE and five SVT. The two-tailed Fisher exact test showed a trend
towards statistical significance (p: 0.06, OR: 3.9, 95% CI 0.87 to 15.3). After
the exclusion of superficial thromboses in both the groups, we found that the
incidence of VTE in our population of women who had undergone ART was 2/234
pregnancies (8.5 0/00), whereas that in our reference population was 6/3339 (1.8
0/00) (p: 0.09). CONCLUSIONS: Our data show a slightly higher incidence of vein
thromboses in pregnancies after ART than in those after natural conception.
PMID- 26443652
TI - Patient-physician mistrust and violence against physicians in Guangdong Province,
China: a qualitative study.
AB - OBJECTIVE: To better understand the origins, manifestations and current policy
responses to patient-physician mistrust in China. DESIGN: Qualitative study using
in-depth interviews focused on personal experiences of patient-physician mistrust
and trust. SETTING: Guangdong Province, China. PARTICIPANTS: One hundred and
sixty patients, patient family members, physicians, nurses and hospital
administrators at seven hospitals varying in type, geography and stages of
achieving goals of health reform. These interviews included purposive selection
of individuals who had experienced both trustful and mistrustful patient
physician relationships. RESULTS: One of the most prominent forces driving
patient-physician mistrust was a patient perception of injustice within the
medical sphere, related to profit mongering, knowledge imbalances and physician
conflicts of interest. Individual physicians, departments and hospitals were
explicitly incentivised to generate revenue without evaluation of caregiving.
Physicians did not receive training in negotiating medical disputes or humanistic
principles that underpin caregiving. Patient-physician mistrust precipitated
medical disputes leading to the following outcomes: non-resolution with patient
resentment towards physicians; violent resolution such as physical and verbal
attacks against physicians; and non-violent resolution such as hospital-mediated
dispute resolution. Policy responses to violence included increased hospital
security forces, which inadvertently fuelled mistrust. Instead of encouraging
communication that facilitated resolution, medical disputes sometimes ignited a
vicious cycle leading to mob violence. However, patient-physician interactions at
one hospital that has implemented a primary care model embodying health reform
goals showed improved patient-physician trust. CONCLUSIONS: The blind pursuit of
financial profits at a systems level has eroded patient-physician trust in China.
Restructuring incentives, reforming medical education and promoting caregiving
are pathways towards restoring trust. Assessing and valuing the quality of
caregiving is essential for transitioning away from entrenched profit-focused
models. Moral, in addition to regulatory and legal, responses are urgently needed
to restore trust.
PMID- 26443653
TI - Study protocol for a controlled trial of Strengths Model Case Management in
mental health services in Hong Kong.
AB - INTRODUCTION: Although strengths-based models are popular within recovery
oriented approaches, there is still a lack of conclusive research to guide how
they should be implemented. A recent meta-analysis confirmed the lack of clarity
in how this perspective is operationalised and that fidelity monitoring during
the implementation process is lacking. Hence, there is a clear need to evaluate
the feasibility of delivering and evaluating a clearly operationalised strengths
based intervention that incorporates fidelity checks to inform more definitive
research. This protocol therefore describes a controlled trial of Strengths Model
Case Management (SMCM), a complex intervention, for people with severe mental
illnesses in Hong Kong. This trial follows the guidelines of the Medical Research
Council as a phase 2 trial. Hence, it is a pilot study that tests the feasibility
and effectiveness of the model. METHODS AND ANALYSIS: This is a 9-month
controlled trial that uses the Kansas Model. Participants and a matched control
group are recruited on a voluntary basis, after screening for eligibility.
Effectiveness of the SMCM will be measured through outcome measures taken at
baseline, the mid-point and at the end of the trial. Outcomes for service users
include personal recovery, hope, subjective well-being, psychiatric symptoms,
perceived level of recovery features within the organisation, therapeutic
alliance and achievement of recovery goals. Outcomes for care workers will
include job burnout, organisational features of recovery and perceived
supervisory support. With a 2*3 analysis of variance design and a moderate
intervention effect (Cohen's d=0.50), a total of 86 participants will be needed
for a statistical power of 0.80. ETHICS AND DISSEMINATION: Ethical approval has
been obtained from the Human Research Ethics Committee for Non-Clinical Faculties
at The University of Hong Kong (HRECNCF: EA140913). TRIAL REGISTRATION NUMBER:
Australian New Zealand Clinical Trial Registry (ACTRN)12613001120763.
PMID- 26443654
TI - Simulation-based multiprofessional obstetric anaesthesia training conducted in
situ versus off-site leads to similar individual and team outcomes: a randomised
educational trial.
AB - OBJECTIVE: To investigate the effect of in situ simulation (ISS) versus off-site
simulation (OSS) on knowledge, patient safety attitude, stress, motivation,
perceptions of simulation, team performance and organisational impact. DESIGN:
Investigator-initiated single-centre randomised superiority educational trial.
SETTING: Obstetrics and anaesthesiology departments, Rigshospitalet, University
of Copenhagen, Denmark. PARTICIPANTS: 100 participants in teams of 10, comprising
midwives, specialised midwives, auxiliary nurses, nurse anaesthetists, operating
theatre nurses, and consultant doctors and trainees in obstetrics and
anaesthesiology. INTERVENTIONS: Two multiprofessional simulations (clinical
management of an emergency caesarean section and a postpartum haemorrhage
scenario) were conducted in teams of 10 in the ISS versus the OSS setting.
PRIMARY OUTCOME: Knowledge assessed by a multiple choice question test.
EXPLORATORY OUTCOMES: Individual outcomes: scores on the Safety Attitudes
Questionnaire, stress measurements (State-Trait Anxiety Inventory, cognitive
appraisal and salivary cortisol), Intrinsic Motivation Inventory and perceptions
of simulations. Team outcome: video assessment of team performance.
Organisational impact: suggestions for organisational changes. RESULTS: The trial
was conducted from April to June 2013. No differences between the two groups were
found for the multiple choice question test, patient safety attitude, stress
measurements, motivation or the evaluation of the simulations. The participants
in the ISS group scored the authenticity of the simulation significantly higher
than did the participants in the OSS group. Expert video assessment of team
performance showed no differences between the ISS versus the OSS group. The ISS
group provided more ideas and suggestions for changes at the organisational
level. CONCLUSIONS: In this randomised trial, no significant differences were
found regarding knowledge, patient safety attitude, motivation or stress
measurements when comparing ISS versus OSS. Although participant perception of
the authenticity of ISS versus OSS differed significantly, there were no
differences in other outcomes between the groups except that the ISS group
generated more suggestions for organisational changes. TRIAL REGISTRATION NUMBER:
NCT01792674.
PMID- 26443655
TI - Clarifying the learning experiences of healthcare professionals with in situ and
off-site simulation-based medical education: a qualitative study.
AB - OBJECTIVE: To examine how the setting in in situ simulation (ISS) and off-site
simulation (OSS) in simulation-based medical education affects the perceptions
and learning experience of healthcare professionals. DESIGN: Qualitative study
using focus groups and content analysis. PARTICIPANTS: Twenty-five healthcare
professionals (obstetricians, midwives, auxiliary nurses, anaesthesiologists, a
nurse anaesthetist and operating theatre nurse) participated in four focus groups
and were recruited due to their exposure to either ISS or OSS in
multidisciplinary obstetric emergencies in a randomised trial. SETTING:
Departments of obstetrics and anaesthesia, Rigshospitalet, Copenhagen, Denmark.
RESULTS: Initially participants preferred ISS, but this changed after the
training when the simulation site became of less importance. There was a strong
preference for simulation in authentic roles. These perceptions were independent
of the ISS or OSS setting. Several positive and negative factors in simulation
were identified, but these had no relation to the simulation setting.
Participants from ISS and OSS generated a better understanding of and
collaboration with the various health professionals. They also provided
individual and team reflections on learning. ISS participants described more
experiences that would involve organisational changes than the OSS participants
did. CONCLUSIONS: Many psychological and sociological aspects related to the
authenticity of the learning experience are important in simulation, but the
physical setting of the simulation as an ISS and OSS is the least important.
Based on these focus groups OSS can be used provided that all other authenticity
elements are taken into consideration and respected. The only difference was that
ISS had an organisational impact and ISS participants talked more about issues
that would involve practical organisational changes. ISS and OSS participants
did, however, go through similar individual and team learning experiences.
PMID- 26443656
TI - Pattern of cardiac surveillance among patients with lymphoma receiving
anthracycline-based chemotherapy.
AB - OBJECTIVE: Anthracyclines are potent antineoplastic agents in the treatment of
lymphoid malignancies, but their therapeutic benefit is limited by
cardiotoxicity. The American Heart Association (AHA) recommends routine
surveillance, early diagnosis and treatment of anthracycline-based chemotherapy
(AC) induced cardiomyopathy (AC-CMP). We aimed to assess the prevalence of AC-CMP
in patients with lymphoma, surveillance patterns of left ventricular ejection
fraction (LVEF) in those receiving AC and management of patients with AC-CMP at
an academic medical centre prior to the development of a comprehensive cardio
oncology programme. METHODS: We performed a retrospective cohort study examining
218 patients with aggressive B cell non-Hodgkin's lymphomas (B-NHL) who received
AC 1992-2012 and had serial follow-up. AC-CMP was defined as LVEF decrease >=10%
with final LVEF<=50% or LVEF reduction >=15% regardless of final LVEF. RESULTS:
Of 218 patients treated with AC, 73 (34%) had LVEF assessment both prior to and
after receiving AC. Of these 73 patients, 24 developed AC-CMP and had higher
cumulative all-cause mortality than those without AC-CMP (HR 2.35, p=0.03).
Coronary artery disease (CAD) was an independent predictor of AC-CMP (p=0.048).
Mean post-AC LVEF was lower in patients with CAD compared with those without CAD
when their baseline LVEF was 45% (p=0.0009) or 55% (p=0.001) but was similar at
65% (p=0.33). Less than half of patients with AC-CMP received recommended heart
failure medication therapy. CONCLUSIONS: Historically, one-third of patients with
B-NHL treated with AC underwent surveillance according to AHA guidelines. There
is substantial opportunity for collaboration between oncologists and
cardiologists to improve the care of patients with lymphoma receiving AC.
PMID- 26443657
TI - Trends in complementary feeding indicators in Nigeria, 2003-2013.
AB - OBJECTIVE: The study aimed to examine secular trends and determinants of changes
in complementary feeding indicators in Nigeria. DESIGN, SETTING AND PARTICIPANTS:
Data on 79 953 children aged 6-23 months were obtained from the Nigeria
Demographic and Health Surveys (NDHS) for the period spanning 2003-2013. The
surveys used a stratified two-stage cluster sample of eligible mothers aged 15-49
years from the six geopolitical zones of Nigeria. Trends in complementary feeding
indicators and socioeconomic, health service and individual characteristics
including factors associated with complementary feeding indicators were examined
using multilevel logistic regression analyses. RESULTS: Minimum dietary diversity
for children aged 6-23 months worsened from 26% in 2003 to 16% in 2013. Minimum
meal frequency improved from 43% in 2003 to 56% in 2013 and minimum acceptable
diet worsened from 11% to 9%. Among educated mothers, there was a decreasing
prevalence of the introduction of solid, semisolid and soft foods in infants aged
6-8 months (67% in 2003 to 57% in 2013); minimum dietary diversity (33% in 2003
to 24% in 2013) and minimum acceptable diet (13% in 2003 to 8% in 2013). Mothers
with a higher education level and mothers who reported more health service
contacts were more likely to meet the minimum dietary diversity. Similarly, the
odds for minimum acceptable diet were higher among mothers from higher
socioeconomic status groups and mothers who reported frequent health services
use. CONCLUSIONS: Complementary feeding practices in Nigeria declined over the
study period and are below the expected levels required to ensure adequate growth
and development of Nigerian children. National policies and programmes that
ensure sustainability of projects post-MDGs and higher health service coverage
for mothers, including community-based education initiatives, are proposed to
improve complementary feeding practices among Nigerian mothers.
PMID- 26443658
TI - Comparative efficacy and acceptability of psychotherapies for acute anxiety
disorders in children and adolescents: study protocol for a network meta
analysis.
AB - INTRODUCTION: Anxiety disorders are associated with significant public health
burden in young individuals. Cognitive-behavioural therapy (CBT) is the most
commonly used psychotherapy for anxiety disorders in children and adolescents,
but previous reviews were hindered by a limited number of trials with direct
comparisons between different psychotherapies and their deliveries. Consequently,
the main aim of this research was to investigate the comparative efficacy and
acceptability of various types and deliveries of psychotherapies for anxiety
disorders in children and adolescents. METHODS AND ANALYSIS: We will
systematically search PubMed, EMBASE, Cochrane, Web of Science, PsycINFO, CINAHL,
ProQuest Dissertations and LiLACS for randomised controlled trials, regardless of
whether participants received blinding or not, published from 1 January 1966 to
30 January 2015 (updated to 1 July 2015), that compared any psychotherapy with
either a control condition or an active comparator with different types and/or
different delivery formats for the acute treatment of anxiety disorders in
children and adolescents. Data extraction, risk of bias and quality assessments
will be independently extracted by two reviewers. The primary outcome for
efficacy will be mean overall change scores in anxiety symptoms (self-rated or
assessor-rated) from baseline to post-treatment between two groups. The
acceptability of treatment will be measured as the proportion of patients who
discontinued treatment during the acute phase of treatment. We will assess
efficacy, based on the standardised mean difference (SMD), and acceptability,
based on the OR, using a random-effects network meta-analysis within a Bayesian
framework. Subgroup and sensitivity analyses will be conducted to assess the
robustness of the findings. ETHICS AND DISSEMINATION: No ethical issues are
foreseen. The results will be published in a peer-reviewed journal and will be
disseminated electronically and in print. The meta-analysis may be updated to
inform and guide management of anxiety in children and adolescents. TRIAL
REGISTRATION NUMBER: PROSPERO CRD42015016283.
PMID- 26443659
TI - Assessing the feasibility of screening and providing brief advice for alcohol
misuse in general dental practice: a clustered randomised control trial protocol
for the DART study.
AB - INTRODUCTION: Alcohol misuse is a significant public health problem with major
health, social and economic consequences. Systematic reviews have reported that
brief advice interventions delivered in various health service settings can
reduce harmful drinking. Although the links between alcohol and oral health are
well established and dentists come into contact with large numbers of otherwise
healthy patients regularly, no studies have been conducted in the UK to test the
feasibility of delivering brief advice about alcohol in general dental settings.
METHODS AND ANALYSIS: The Dental Alcohol Reduction Trial (DART) aims to assess
the feasibility and acceptability of screening for alcohol misuse and delivering
brief advice in patients attending National Health Service (NHS) general dental
practices in North London. DART is a cluster randomised control feasibility trial
and uses a mixed methods approach throughout the development, design, delivery
and evaluation of the intervention. It will be conducted in 12 NHS general dental
practices across North London and will include dental patients who drink above
the recommended guidance, as measured by the Alcohol Use Disorders Identification
Test (AUDIT-C) screening tool. The intervention involves 5 min of tailored brief
advice delivered by dental practitioners during the patient's appointment.
Feasibility and acceptability measures as well as suitability of proposed primary
outcomes of alcohol consumption will be assessed. Initial economic evaluation
will be undertaken. Recruitment and retention rates as well as acceptability of
the study procedures from screening to follow-up will be measured. ETHICS AND
DISSEMINATION: Ethical approval was obtained from the Camden and Islington
Research Ethics Committee. Study outputs will be disseminated via scientific
publications, newsletters, reports and conference presentations to a range of
professional and patient groups and stakeholders. Based on the results of the
trial, recommendations will be made on the conduct of a definitive randomised
controlled trial. TRIAL REGISTRATION NUMBER: ISRCTN81193263.
PMID- 26443660
TI - Longitudinal qualitative exploration of cancer information-seeking experiences
across the disease trajectory: the INFO-SEEK protocol.
AB - INTRODUCTION: Alpha substantial corpus of literature has sought to describe the
information-seeking behaviour of patients with cancer. Yet, available evidence
comes mainly from cross-sectional studies, which provide 'snapshots' of patients'
information needs and information-seeking styles at a single time point. Only a
few longitudinal studies currently exist; however, these are quantitative in
nature and, despite successfully documenting changes in patients' information
needs throughout the clinical course of cancer, they have failed to provide an
evidence-based interpretation of the causes and consequences of change. The goal
of this study is threefold: First, we wish to provide a holistic understanding of
how cancer information-seeking behaviour may evolve across different stages of
the patient journey. Second, we will seek to elucidate the contextual and
intervening conditions that may affect possible changes in information seeking.
Third, we will attempt to identify what the consequences of these changes are,
while heightening their implications for clinical practice and policy. METHODS
AND ANALYSIS: We will carry out a longitudinal qualitative study, based on face
to-face, in-depth interviews with approximately 25 individuals diagnosed with
cancer. Patients will be recruited from 2 oncology hospitals located in Ticino,
Switzerland, and will be interviewed at 3 different time points: (1) within 2
weeks after receiving the cancer diagnosis; (2) within 2 weeks after their
initial treatment; and (3) 6 months after their initial treatment. All interviews
will be recorded and transcribed verbatim. A grounded theory approach will be
used for the analysis of the data. ETHICS AND DISSEMINATION: The study protocol
has been approved by the Ethics Committee of Canton Ticino (CE 2813).
Participation in the study will be voluntary, and confidentiality and anonymity
ensured. Prior to study participation, patients will be asked to provide signed
informed consent. Findings will be disseminated in international peer-reviewed
journals and presented in relevant conferences.
PMID- 26443661
TI - Longitudinal cohort study describing persistent frequent attenders in Australian
primary healthcare.
AB - OBJECTIVES: To describe patterns of frequent attendance in Australian primary
care, and identify the prospective risk factors for persistent frequent
attendance. DESIGN, SETTING AND PARTICIPANTS: This study draws on data from the
Personality and Total Health (PATH) Through Life Project, a representative
community cohort study of residents from the Canberra region of Australia.
Participants were assessed on 3 occasions over 8 years. The survey assessed
respondents' experience of chronic physical conditions, self-reported health,
symptoms of common mental disorders, personality, life events, sociodemographic
characteristics and self-reported medication use. A balanced sample was used in
analysis, comprising 1734 respondents with 3 waves of data. The survey data for
each respondent were individually linked to their administrative health service
use data which were used to generate an objective measure of general practitioner
(GP) consultations in the 12 months surrounding their interview date. MAIN
OUTCOME MEASURES: Respondents in the (approximate) highest decile of attenders on
number of GP consultations over a 12-month period at each time point were defined
as frequent attenders (FAs). RESULTS: Baseline FAs (8.4%) were responsible for
33.4% of baseline consultations, while persistent FAs (3.6%) for 15.5% of all
consultations over the 3 occasions. While there was considerable movement between
FA status over time, consistency was greater than expected by chance alone. While
there were many factors that differentiated non-FAs from FAs in general,
persistent frequent attendance was specifically associated with gender, baseline
reports of depression, self-reported physical conditions and disability, and
medication use. CONCLUSIONS: The degree of persistence in GP consultations was
limited. The findings of this study contribute to our understanding of the risk
factors that predict subsequent persistent frequent attendance in primary care.
However, further detailed investigation of longitudinal patterns of frequent
attendance and consideration of time-varying determinants of frequent attendance
is required.
PMID- 26443662
TI - Development of the Serious Illness Care Program: a randomised controlled trial of
a palliative care communication intervention.
AB - INTRODUCTION: Ensuring that patients receive care that is consistent with their
goals and values is a critical component of high-quality care. This article
describes the protocol for a cluster randomised controlled trial of a
multicomponent, structured communication intervention. METHODS AND ANALYSIS:
Patients with advanced, incurable cancer and life expectancy of <12 months will
participate together with their surrogate. Clinicians are enrolled and randomised
either to usual care or the intervention. The Serious Illness Care Program is a
multicomponent, structured communication intervention designed to identify
patients, train clinicians to use a structured guide for advanced care planning
discussion with patients, 'trigger' clinicians to have conversations, prepare
patients and families for the conversation, and document outcomes of the
discussion in a structured format in the electronic medical record. Clinician
satisfaction with the intervention, confidence and attitudes will be assessed
before and after the intervention. Self-report data will be collected from
patients and surrogates approximately every 2 months up to 2 years or until the
patient's death; patient medical records will be examined at the close of the
study. Analyses will examine the impact of the intervention on the patient
receipt of goal-concordant care, and peacefulness at the end of life. Secondary
outcomes include patient anxiety, depression, quality of life, therapeutic
alliance, quality of communication, and quality of dying and death. Key process
measures include frequency, timing and quality of documented conversations.
ETHICS AND DISSEMINATION: This study was approved by the Dana-Farber Cancer
Institute Institutional Review Board. Results will be reported in peer-reviewed
publications and conference presentations. TRIAL REGISTRATION NUMBER: Protocol
identifier NCT01786811; Pre-results.
PMID- 26443664
TI - Correction: Therapeutic Peptide Vaccine-Induced CD8 T Cells Strongly Modulate
Intratumoral Macrophages Required for Tumor Regression.
PMID- 26443663
TI - The EARN-Health Trial: protocol for a randomised controlled trial to identify
health effects of a financial savings programme among low-income US adults.
AB - INTRODUCTION: A theory within the social epidemiology field is that financial
stress related to having inadequate financial savings may contribute to
psychological stress, poor mental health and poor health-related behaviours among
low-income US adults. Our objective is to test whether an intervention that
encourages financial savings among low-income US adults improves health
behaviours and mental health. METHODS AND ANALYSIS: A parallel group two-arm
controlled superiority trial will be performed in which 700 participants will be
randomised to the intervention or a wait list. The intervention arm will be
provided an online Individual Development Account (IDA) for 6 months, during
which participants receive a $5 incentive (L3.2, ?4.5) for every month they save
$20 in their account (L12.8, ?18), and an additional $5 if they save $20 for two
consecutive months. Both groups will be provided links to standard online
financial counselling materials. Online surveys in months 0 (prior to
randomisation), 6 and 12 (6 months postintervention) will assess self-reported
health behaviours and mental health among participants in both arms. The surveys
items were tested previously in the US Centers for Disease Control and Prevention
national health interviews and related health studies, including self-reported
overall health, health-related quality of life, alcohol and tobacco use,
depression symptoms, financial stress, optimism and locus of control, and
spending and savings behaviours. Trial data will be analysed on an intent-to
treat basis. ETHICS AND DISSEMINATION: This protocol was approved by the
Institutional Review Board of Stanford University (Protocol ID: 30641). The
findings of the trial will be disseminated through peer-reviewed publication.
TRIAL REGISTRATION NUMBER: Identifier NCT02185612; Pre-results.
PMID- 26443665
TI - Influence of provider mix and regulation on primary care services supplied to US
patients.
AB - Access to medical care and how it differs for various patients remain key policy
issues. While existing work has examined clinic structure's influence on
productivity, less research has explored the link between provider mix and access
for different patient types - which also correspond to different service prices.
We exploit experimental data from a large field study spanning 10 US states where
trained audit callers were randomly assigned an insurance status and then
contacted primary care physician practices seeking new patient appointments. We
find clinics with more non-physician clinicians are associated with better access
for Medicaid patients and lower prices for office visits; however, these
relationships are only found in states granting full practice autonomy to these
providers. Substituting more non-physician labor in primary care settings may
facilitate greater appointment availability for Medicaid patients, but this
likely rests on a favorable policy environment. Relaxing regulations for non
physicians may be an important initiative as US health reforms continue and also
relevant to other countries coping with greater demands for medical care and
related financial strain.
PMID- 26443666
TI - The Impact of Age on 5-Year Outcomes After Atrial Fibrillation Catheter Ablation.
AB - BACKGROUND: Catheter ablation of atrial fibrillation (AF) is an established
therapeutic rhythm approach in symptomatic patients. Many studies have shown that
age has little to no impact on outcomes during the first year after ablation.
However, AF is a disease of aging and age-based substrate for arrhythmia is
likely to progress. To this regard, we examined patients with 5-year outcome data
following an index AF ablation procedure to define the impact of age on long-term
outcomes. METHODS: A total of 923 patients that underwent their index AF ablation
and had 5 years of follow-up were studied. Patients were followed up for atrial
flutter/AF recurrence, heart failure, stroke, death, and cardiac function.
Patients were separated and compared in 5 age-based groups (<50, 51-60, 61-70, 71
80, >80). RESULTS: The average age of the population was 66 +/- 11 years and 59%
were male. The AF was paroxysmal in 55%, persistent in 27%, and longstanding
persistent in 18%. Older patients were more likely female and had higher rates of
cardiovascular diseases. For every 10-year increase in age there was a higher
multivariate-adjusted risk of atrial flutter/AF recurrence (HR: 1.13, P = 0.01),
death (HR:1.91, P < 0.0001), and major adverse cardiac events (HR: 1.09, P =
0.07). Although atrial flutter/AF recurrence rates by age were similar at 1 year,
at 5 years, younger patients had significantly lower rates of recurrences.
CONCLUSION: Age significantly impacts outcomes after AF ablation when analyzed
with long-term follow-up. These data highlight the progressive nature of AF and
the need to consider interventions early.
PMID- 26443668
TI - A Sleep Like Death: Identification of Genes Related to Seed Longevity in Medicago
truncatula and Arabidopsis.
PMID- 26443667
TI - CELLULOSE SYNTHASE INTERACTIVE1 Is Required for Fast Recycling of Cellulose
Synthase Complexes to the Plasma Membrane in Arabidopsis.
AB - Plants are constantly subjected to various biotic and abiotic stresses and have
evolved complex strategies to cope with these stresses. For example, plant cells
endocytose plasma membrane material under stress and subsequently recycle it back
when the stress conditions are relieved. Cellulose biosynthesis is a tightly
regulated process that is performed by plasma membrane-localized cellulose
synthase (CESA) complexes (CSCs). However, the regulatory mechanism of cellulose
biosynthesis under abiotic stress has not been well explored. In this study, we
show that small CESA compartments (SmaCCs) or microtubule-associated cellulose
synthase compartments (MASCs) are critical for fast recovery of CSCs to the
plasma membrane after stress is relieved in Arabidopsis thaliana. This SmaCC/MASC
mediated fast recovery of CSCs is dependent on CELLULOSE SYNTHASE INTERACTIVE1
(CSI1), a protein previously known to represent the link between CSCs and
cortical microtubules. Independently, AP2M, a core component in clathrin-mediated
endocytosis, plays a role in the formation of SmaCCs/MASCs. Together, our study
establishes a model in which CSI1-dependent SmaCCs/MASCs are formed through a
process that involves endocytosis, which represents an important mechanism for
plants to quickly regulate cellulose synthesis under abiotic stress.
PMID- 26443669
TI - Lipomatous metaplasia of superficial dermis.
AB - Lipomatous metaplasia is an uncommon phenomenon. After identifying the presence
of a band of adipocytes in the superficial reticular dermis underlying two
excisions for basal cell carcinoma, we prospectively reviewed all skin specimens
accessioned in our laboratory over a 6-month period and identified eight
additional cases. In each example there was a band of adipocytes in the upper
dermis, at the level of solar elastosis that was widely separated from the
subcutaneous fat by a normal appearing reticular dermis. The cells were positive
for S100 and negative for CD163. No connection between the superficial band of
adipocytes and the subcutaneous or periappendageal fat was seen. The alterations
were flat in configuration without polypoid changes. Eyerich et al. reported
lipomatous metaplasia in the dermis of a patient with acute generalized
exanthematic pustulosis and psoriasis, and postulated this to be a
postinflammatory phenomenon. Fatty metaplasia occurs within a variety of
cutaneous neoplasms including nevi, adnexal tumors and peripheral nerve sheath
tumors. However, superficial dermal fatty metaplasia beneath cutaneous neoplasms
is a newly described phenomenon and we suspect this process represents fatty
metaplasia within solar elastosis and that it may occur more frequently than
recognized.
PMID- 26443670
TI - Promoting psychosocial adaptation of youths in residential care through animal
assisted psychotherapy.
AB - The goal of this study was to examine the influence of animal-assisted
psychotherapy (AAP) on the psychosocial adaptation of a group of adolescents in
residential care who had suffered traumatic childhood experiences and who
presented with mental health problems. This study recruited 63 youths (mean
age=15.27, SD=1.63) who were divided into two groups: a treatment group of 39
youths (19 female and 20 male; mean age=15.03, SD=0.51) and a control group of 24
(five female and 19 male; mean age=15.67, SD=1.63). The youths who underwent the
AAP program had higher school adjustment in comparison to their peers who did not
receive treatment. Their hyperactive behavior decreased, and they showed better
social skills, more leadership, and fewer attention problems. They also showed a
more positive attitude toward their teachers in comparison to controls. No
differences were observed in other variables associated with clinical symptoms or
personal adjustment. These results suggest that AAP can be effective with
teenagers who have suffered childhood traumas and who present with problems of
psychosocial adaptation.
PMID- 26443671
TI - Health Literacy Among People with Serious Mental Illness.
AB - People diagnosed with a mental illness are at higher risk of developing
preventable chronic diseases; thus, health literacy improvements may have great
potential to impact health outcomes for this typically underserved population.
However, there is a dearth of research on health literacy of persons with severe
mental illness. The purpose of this research was to investigate aspects of health
literacy and identify factors associated with low literacy among adults with
severe mental illness using three literacy assessment tools. Seventy-one adults
with serious mental illness were assessed and a high proportion had limited
literacy levels: 42% with the Single Item Literacy Screener, 50% with the Rapid
Estimate of Adult Literacy in Medicine-Short Form, and 67% with the Newest Vital
Sign. Findings suggest that individuals with certain mental illnesses and lower
functioning may have more difficulty understanding health information and have
limited numerical literacy.
PMID- 26443672
TI - Novel environmental species isolated from the plaster wall surface of mural
paintings in the Takamatsuzuka tumulus: Bordetella muralis sp. nov., Bordetella
tumulicola sp. nov. and Bordetella tumbae sp. nov.
AB - Ten strains of Gram-stain-negative, non-spore-forming, non-motile coccobacilli
were isolated from the plaster wall surface of 1300-year-old mural paintings
inside the stone chamber of the Takamatsuzuka tumulus in Asuka village (Asuka
mura), Nara Prefecture, Japan. Based on 16S rRNA gene sequence analysis of the
isolates, they belonged to the proteobacterial genus Bordetella (class
Betaproteobacteria) and could be separated into three groups representing novel
lineages within the genus Bordetella. Three isolates were selected, one from each
group, and identified carefully using a polyphasic approach. The isolates were
characterized by the presence of Q-8 as their major ubiquinone system and C16 : 0
(30.0-41.8 %), summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c; 10.1-27.0
%) and C17 : 0 cyclo (10.8-23.8 %) as the predominant fatty acids. The major
hydroxy fatty acids were C12 : 0 2-OH and C14 : 0 2-OH. The DNA G+C content was
59.6-60.0 mol%. DNA-DNA hybridization tests confirmed that the isolates
represented three separate novel species, for which the names Bordetella muralis
sp. nov. (type strain T6220-3-2bT = JCM 30931T = NCIMB 15006T), Bordetella
tumulicola sp. nov. (type strain T6517-1-4bT = JCM 30935T = NCIMB 15007T) and
Bordetella tumbae sp. nov. (type strain T6713-1-3bT = JCM 30934T = NCIMB 15008T)
are proposed. These results support previous evidence that members of the genus
Bordetella exist in the environment and may be ubiquitous in soil and/or water.
PMID- 26443673
TI - Neofunctionalization of a Duplicate dachshund Gene Underlies the Evolution of a
Novel Leg Segment in Arachnids.
AB - The acquisition of a novel function, or neofunctionalization, protects duplicated
genes from redundancy and subsequent loss, and is a major force that drives
adaptive evolution. Neofunctionalization has been inferred for many duplicated
genes based on differences in regulation between the parental gene and its
duplicate. However, only few studies actually link the new function of a
duplicated gene to a novel morphological or physiological character of the
organism. Here we show that the duplication of dachshund (dac) in arachnids
(spiders and allies) is linked with the evolution of a novel leg segment, the
patella. We have studied dac genes in two distantly related spider species, the
entelegyne spider Parasteatoda tepidariorum and the haplogyne spider Pholcus
phalangioides. Both species possess two paralogous dac genes that duplicated
before the split between entelegyne and haplogyne spiders. In contrast to the
evolutionarily highly conserved dac1, its duplicate dac2 is strongly expressed in
the patella leg segment during embryogenesis in both species. Using parental RNA
interference in P. tepidariorum we show that dac2 is required for the development
of the patella segment. If dac2 function is impaired, then the patella is fused
with the tibia into a single leg segment. Thus, removing the function of dac2
experimentally reverts P. tepidariorum leg morphology into a stage before the
duplication of dac and the evolution of the patella segment. Our results indicate
that the origin of the patella is the result of the duplication and subsequent
neofunctionalization of dac in the arachnid lineage.
PMID- 26443674
TI - Life in standby: hemodialysis patients' experiences of waiting for kidney
transplantation.
AB - AIM AND OBJECTIVES: Our aim was to explore the experiences of hemodialysis
patients who are waiting for a kidney transplant. BACKGROUND: Currently, more
than 100,000 persons are waiting for kidney transplantation in the United States.
In Sweden, the number is exceeding 600. The waiting period for a deceased donor
can be one to three years or even longer in Sweden. This can be challenging,
since the patients' situation, with chronic treatment and illness, is burdensome
and requires advanced self-care. DESIGN: This study included a purposeful sample
of eight patients (33-53 years old) who had been undergoing hemodialysis
treatment for at least six months and were waiting for kidney transplantation.
METHODS: The patients were interviewed, and descriptive content analysis was
performed. RESULTS: Four categories emerged: (1) 'The waiting process,' what
thoughts and expectations occur and what to do and how to be prepared for the
transplant. (2) 'Awareness that time is running out,' patients felt tied up by
treatment and by needing to be available for transplantation, and they had
concerns about health. (3) 'Need for communication,' patients described needing
support from others and continuous information from the staff. (4) 'Having relief
and hope for the future,' patients described how to preserve the hope of being
able to participate fully in life once again. CONCLUSIONS: This study reveals the
need for extra attention paid to patients waiting for kidney transplantation.
Patients' experiences during the waiting period indicate that pretransplant
patients have an increased need to be prepared for the transition and for life
post-transplantation. RELEVANCE TO CLINICAL PRACTICE: Dialysis patients on
waiting lists must be prepared for the upcoming life change. This includes
preserving hope during the waiting period and being mentally prepared for
transplantation and a dialysis-free life. A pretransplant education program to
prevent medical and psychosocial issues is highly recommended.
PMID- 26443675
TI - Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A
Systematic Review of Human Studies.
AB - Autism spectrum disorders are an emerging health problem worldwide, but little is
known about their pathogenesis. It has been hypothesized that autism may result
from an imbalance between excitatory glutamatergic and inhibitory GABAergic
pathways. Commonly used medications such as valproate, acamprosate, and
arbaclofen may act on the GABAergic system and be a potential treatment for
people with ASD. The present systematic review aimed at evaluating the state-of
the-art of clinical trials of GABA modulators in autism. To date there is
insufficient evidence to suggest the use of these drugs in autistic subjects,
even if data are promising. Of note, short-term use of all the reviewed
medications appears to be safe. Future well designed trials are needed to
elucidate these preliminary findings.
PMID- 26443676
TI - The Tomato MIXTA-Like Transcription Factor Coordinates Fruit Epidermis Conical
Cell Development and Cuticular Lipid Biosynthesis and Assembly.
AB - The epidermis of aerial plant organs is the primary source of building blocks
forming the outer surface cuticular layer. To examine the relationship between
epidermal cell development and cuticle assembly in the context of fruit surface,
we investigated the tomato (Solanum lycopersicum) MIXTA-like gene. MIXTA/MIXTA
like proteins, initially described in snapdragon (Antirrhinum majus) petals, are
known regulators of epidermal cell differentiation. Fruit of transgenically
silenced SlMIXTA-like tomato plants displayed defects in patterning of conical
epidermal cells. They also showed altered postharvest water loss and resistance
to pathogens. Transcriptome and cuticular lipids profiling coupled with
comprehensive microscopy revealed significant modifications to cuticle assembly
and suggested SlMIXTA-like to regulate cutin biosynthesis. Candidate genes likely
acting downstream of SlMIXTA-like included cytochrome P450s (CYPs) of the CYP77A
and CYP86A subfamilies, LONG-CHAIN ACYL-COA SYNTHETASE2, GLYCEROL-3-PHOSPHATE SN
2-ACYLTRANSFERASE4, and the ATP-BINDING CASSETTE11 cuticular lipids transporter.
As part of a larger regulatory network of epidermal cell patterning and L1-layer
identity, we found that SlMIXTA-like acts downstream of SlSHINE3 and possibly
cooperates with homeodomain Leu zipper IV transcription factors. Hence, SlMIXTA
like is a positive regulator of both cuticle and conical epidermal cell formation
in tomato fruit, acting as a mediator of the tight association between fruit
cutin polymer formation, cuticle assembly, and epidermal cell patterning.
PMID- 26443677
TI - RNA Silencing of Exocyst Genes in the Stigma Impairs the Acceptance of Compatible
Pollen in Arabidopsis.
AB - Initial pollen-pistil interactions in the Brassicaceae are regulated by rapid
communication between pollen grains and stigmatic papillae and are fundamentally
important, as they are the first step toward successful fertilization. The goal
of this study was to examine the requirement of exocyst subunits, which function
in docking secretory vesicles to sites of polarized secretion, in the context of
pollen-pistil interactions. One of the exocyst subunit genes, EXO70A1, was
previously identified as an essential factor in the stigma for the acceptance of
compatible pollen in Arabidopsis (Arabidopsis thaliana) and Brassica napus. We
hypothesized that EXO70A1, along with other exocyst subunits, functions in the
Brassicaceae dry stigma to deliver cargo-bearing secretory vesicles to the
stigmatic papillar plasma membrane, under the pollen attachment site, for pollen
hydration and pollen tube entry. Here, we investigated the functions of exocyst
complex genes encoding the remaining seven subunits, SECRETORY3 (SEC3), SEC5,
SEC6, SEC8, SEC10, SEC15, and EXO84, in Arabidopsis stigmas following compatible
pollinations. Stigma-specific RNA-silencing constructs were used to suppress the
expression of each exocyst subunit individually. The early postpollination stages
of pollen grain adhesion, pollen hydration, pollen tube penetration, seed set,
and overall fertility were analyzed in the transgenic lines to evaluate the
requirement of each exocyst subunit. Our findings provide comprehensive evidence
that all eight exocyst subunits are necessary in the stigma for the acceptance of
compatible pollen. Thus, this work implicates a fully functional exocyst complex
as a component of the compatible pollen response pathway to promote pollen
acceptance.
PMID- 26443678
TI - Roseomonas oryzicola sp. nov., isolated from the rhizosphere of rice (Oryza
sativa L.).
AB - A Gram-stain-negative, coccobacilli-shaped bacterium, designated YC6724T, was
isolated from the rhizosphere of rice in Jinju, Korea. The taxonomy of strain
YC6724T was studied using a polyphasic approach. Strain YC6724T grew optimally at
30 degrees C and pH 7.0-8.0. Comparative 16S rRNA gene sequence analyses showed
that the strain was most closely related to Roseomonas soli 5N26T (98.4 % 16S
rRNA gene sequence similarity), Roseomonas lacus THG33T(97.3 %) and Roseomonas
terrae DS-48T (97.3 %). Sequence similarities with other species of the genus
Roseomonas with validly published names were lower than 94.0 %. Phylogenetic
analysis based on the 16S rRNA gene sequence showed that strain YC6724T formed a
distinct phyletic lineage within the genus Roseomonas. Strain YC6724T had DNA-DNA
relatedness values of 16.6 %, 44.0 % and 33.2 % with R. soli KACC 16376T, R.
terrae KACC 12677T and R. lacus KACC 11678T, respectively. The predominant fatty
acids of strain YC6724T were C18 : 1omega7c and/or C18 : 1omega6c, C16 : 0 and
C18 : 1 2-OH. The polar lipid profile contained phosphatidylethanolamine,
phosphatidylcholine, phosphatidylglycerol,diphosphatidylglycerol, an unknown
aminolipid and two unknown lipids. The G+C content of the genomic DNA was 70.5
mol% and the major quinone was Q-10. Strain YC6724T contained spermidine as the
major polyamine. On the basis of phenotypic, chemotaxonomic and molecular data,
it is clear that strain YC6724T represents a novel species of the genus
Roseomonas, for which the name Roseomonas oryzicola sp. nov. is proposed. The
type strain is YC6724T (=KCTC 22478T=NBRC 109439T).
PMID- 26443679
TI - Cumulative stress in childhood is associated with blunted reward-related brain
activity in adulthood.
AB - Early life stress (ELS) is strongly associated with negative outcomes in
adulthood, including reduced motivation and increased negative mood. The
mechanisms mediating these relations, however, are poorly understood. We examined
the relation between exposure to ELS and reward-related brain activity, which is
known to predict motivation and mood, at age 26, in a sample followed since
kindergarten with annual assessments. Using functional neuroimaging, we assayed
individual differences in the activity of the ventral striatum (VS) during the
processing of monetary rewards associated with a simple card-guessing task, in a
sample of 72 male participants. We examined associations between a cumulative
measure of ELS exposure and VS activity in adulthood. We found that greater
levels of cumulative stress during childhood and adolescence predicted lower
reward-related VS activity in adulthood. Extending this general developmental
pattern, we found that exposure to stress early in development (between
kindergarten and grade 3) was significantly associated with variability in adult
VS activity. Our results provide an important demonstration that cumulative life
stress, especially during this childhood period, is associated with blunted
reward-related VS activity in adulthood. These differences suggest
neurobiological pathways through which a history of ELS may contribute to reduced
motivation and increased negative mood.
PMID- 26443680
TI - [Current aspects on the management of normal tension glaucoma].
AB - In a considerable proportion of glaucoma patients (25-50 %) the intraocular
pressure (IOP) is not elevated higher than 22 mmHg at first diagnosis and during
subsequent follow-up controls. Although the IOP level remains in the low range <
22 mmHg, progression of glaucoma can still occur. A multitude of different
factors are assumed to be involved in glaucoma progression, such as very low
nocturnal diastolic blood pressure values, a low mean ocular perfusion pressure,
extensive fluctuations in perfusion (e.g. in cases of vascular dysregulation), an
increased vulnerability of the optic nerve support structures, an increased
translaminar pressure gradient and various underlying systemic diseases. The most
important evidence-based aspect of treatment in normal tension glaucoma is
pharmaceutical or surgical reduction of the IOP by 30 % or more in comparison to
the initial pressure level. Vascular and neuroprotective concepts of treatment
for normal tension glaucoma have been strongly advocated and the object of
experimental and clinical studies. As yet a clear clinical benefit has not been
proven by large prospective randomized studies.
PMID- 26443681
TI - Nocardioides ungokensis sp. nov., isolated from lake sediment.
AB - A Gram-reaction-positive, aerobic, coccus- to rod-shaped, non-motile, non-spore
forming bacterium (strain UKS-03T) was isolated from a sediment sample of Ungok
Lake in Gochang, Republic of Korea. The taxonomic position of this bacterium was
determined in an investigation based on a polyphasic approach. On the basis of
16S rRNA gene sequence analysis, strain UKS-03T was shown to belong to the family
Nocardioidaceae and to be related most closely to Nocardioides ginsengisegetis
Gsoil 485T (98.5 % similarity), Nocardioides koreensis MSL-09T (98.4 %) and
'Nocardioides panaciterrulae' Gsoil 958 (97.3 %). Strain UKS-03T was
characterized chemotaxonomically as having ll-2,6-diaminopimelic acid in its cell
wall peptidoglycan, MK-8(H4) as the predominant menaquinone,
diphosphatidylglycerol and phosphatidylglycerol as the main polar lipids, and iso
C16 : 0, C17 : 1omega8c and C17 : 0 10-methyl as its major fatty acids. The G+C
content of the genomic DNA was 71.9 mol%. Mean DNA-DNA relatedness values between
strain UKS-03T and N. ginsengisegetis Gsoil 485T, N. koreensis KCTC 19272T and
'N. panaciterrulae' Gsoil 958 were 37.5 +/- 7.2, 6.8 +/- 0.9 and 3.1 +/- 0.7 %,
respectively. On the basis of the data from this polyphasic taxonomic study,
strain UKS-03T represents a novel species of the genus Nocardioides, for which
the name Nocardioides ungokensis sp. nov. is proposed. The type strain is UKS-03T
( = KACC 18304T = LMG 28591T).
PMID- 26443682
TI - Reward memory relieves anxiety-related behavior through synaptic strengthening
and protein kinase C in dentate gyrus.
AB - Anxiety disorders are presumably associated with negative memory. Psychological
therapies are widely used to treat this mental deficit in human beings based on
the view that positive memory competes with negative memory and relieves anxiety
status. Cellular and molecular processes underlying psychological therapies
remain elusive. Therefore, we have investigated its mechanisms based on a mouse
model in which food reward at one open-arm of the elevated plus-maze was used for
training mice to form reward memory and challenge the open arms. Mice with the
reward training showed increased entries and stay time in reward open-arm versus
neutral open-arm as well as in open-arms versus closed-arms. Accompanying with
reward memory formation and anxiety relief, glutamatergic synaptic transmission
in dentate gyrus in vivo and dendritic spines in granule cells became
upregulated. This synaptic up-regulation was accompanied by the expression of
more protein kinase C (PKC) in the dendritic spines. The inhibition of PKC by
chelerythrine impaired the formation of reward memory, the relief of anxiety
related behavior and the up-regulation of glutamate synapses. Our results suggest
that reward-induced positive memory relieves mouse anxiety-related behavior by
strengthening synaptic efficacy and PKC in the hippocampus, which imply the
underlying cellular and molecular processes involved in the beneficial effects of
psychological therapies treating anxiety disorders.
PMID- 26443683
TI - Writing throughout the biochemistry curriculum: Synergistic inquiry-based writing
projects for biochemistry students.
AB - This article describes a synergistic two-semester writing sequence for
biochemistry courses. In the first semester, students select a putative protein
and are tasked with researching their protein largely through bioinformatics
resources. In the second semester, students develop original ideas and present
them in the form of a research grant proposal. Both projects involve multiple
drafts and peer review. The complementarity of the projects increases student
exposure to bioinformatics and literature resources, fosters higher-order
thinking skills, and develops teamwork and communication skills. Student feedback
and responses on perception surveys demonstrated that the students viewed both
projects as favorable learning experiences.
PMID- 26443684
TI - Where are the sensory organs of Nybelinia surmenicola (Trypanorhyncha)? A
comparative analysis with Parachristianella sp. and other trypanorhynchean
cestodes.
AB - The sensory organs in tegument of two trypanorhynchean species--Nybelinia
surmenicola (plerocercoid) and adult Parachristianella sp. (Cestoda,
Trypanorhyncha)--were studied with the aim of ultrastructural description and a
comparative analysis. The Nybelinia surmenicola plerocercoid lacks papillae with
sensory cilia on the bothria adhesive surface. We found an unciliated sensory
organ within the median bothria fold. This unciliated free nerve ending contains
the central electron-dense disc, three dense supporting rings, and broad root.
The nerve ending locates in the basal matrix under the tegument. The tegument of
N. surmenicola has a number of ultrastructural features which make it
significantly different from other Trypanorhyncha: (i) the tegumental cytoplasm
has a plicated constitution in a form of high apical and deep basal folds, (ii)
numerous layers of the basal matrix are presented in the subtegument, and (iii)
the squamiform and bristlelike microtriches N. surmenicola lack the base and the
basal plate. In contrast, numerous ciliated and unciliated receptors were found
in Parachristianella sp.: six types on the bothria and one type in the strobila
tegument. Ultrastructural constitution of sensory organs in the form of ciliated
free nerve endings as well as unciliated basal nerve endings of Parachristianella
sp. has many common features inside Eucestoda. In comparison with other
Trypanorhyncha, all Nybelinia species studied have less quantity of the bothrial
sensory organs. This fact may reflect behavioral patterns of Nybelinia as well as
phylogenetic position into Trypanorhyncha. Our observations of living animals
conventionally demonstrate the ability of N. surmenicola plerocercoids to
locomote in forward direction on the Petri dish surface. The participation of the
bothrial microtriches in a parasite movement has been discussed.
PMID- 26443685
TI - The diversity and prevalence of hard ticks attacking human hosts in Eastern
Siberia (Russian Federation) with first description of invasion of non-endemic
tick species.
AB - Hard ticks are the vectors of many pathogens including tick-borne encephalitis
virus and the Lyme disease agent Borrelia burgdorferi sensu lato. In Eastern
Siberia, Ixodes persulcatus, Dermacentor nuttalli, Dermacentor silvarum and
Haemaphysalis concinna are regarded as aggressive to humans. Recently,
significant changes in world tick fauna have been reported and this affects the
spread of tick-borne pathogens. We studied the current species diversity,
population structure and prevalence of tick-borne pathogens of hard ticks (Acari:
Ixodidae) that attacked humans in Eastern Siberia (Irkutsk region, Russia). In
total, 31,892 individual ticks were identified and analysed during the years 2007
2014. The majority (85.4%) of victims was bitten by I. persulcatus, 14.55% of
attacks on humans were caused by D. nuttalli and D. silvarum, whereas H. concinna
was documented only in 15 cases (0.05%). The seasonal activity and the age/gender
structure of the tick population were studied as well. Among all the studied
ticks, three unconventional species, i.e. Rhipicephalus sanguineus, Dermacentor
reticulatus and Amblyomma americanum, were identified. Analysis of tick bite
histories indicates at least three events of invasion of non-endemic ticks into
the ecosystems of northern Eurasia with harsh continental climates. Invading
ticks are able to reach the adult life stage and are aggressive to the local
human population. Phylogenetic analysis of mt 16S rRNA gene fragments suggests
multiple independent routes of tick migration to Eastern Siberia. Possible
implications to human health and epidemiology of tick-borne infections are
discussed.
PMID- 26443686
TI - A molecular perspective on rituximab: A monoclonal antibody for B cell non
Hodgkin lymphoma and other affections.
AB - Rituximab (a chimeric anti-CD20 monoclonal antibody) is the first Food and Drug
Administration approved anti-tumor antibody. Immunotherapy by rituximab,
especially in combination-therapy, is a mainstay for a vast variety of B-cell
malignancies therapy. Its therapeutic value is unquestionable, yet the mechanisms
of action responsible for anti-tumor activity of rituximab and rituximab
resistance mechanisms are not completely understood. Investigation of the
mechanisms of action that contribute to the rituximab activity have eventually
directed to a suite of novel combinations and novel treatment schedules, and also
have resulted new generations of antibodies with more desired effects. Although,
further investigations are needed to define the mechanisms of rituximab
resistance and prominent effector activity of the altered next generation anti
CD20 to improve their efficacies and develop new anti-CD20 monoclonal antibodies
in NHL treatment. This article focuses on the properties of CD20 which led
scientists to select it as an effective therapeutic target and the molecular
details of mechanisms of rituximab action and resistance. We also discuss about
the impact of rituximab in monotherapy and in combination with chemotherapy
regimens. Finally, we comparatively summarize the next generations of anti CD20
monoclonal antibodies to highlight their advantages relative to their ancestor:
Rituximab.
PMID- 26443687
TI - A simple assessment model to quantifying the dynamic hippocampal neurogenic
process in the adult mammalian brain.
AB - Adult hippocampal neurogenesis is a highly dynamic process in which new cells are
born, but only some of which survive. Of late it has become clear that these
surviving newborn neurons have functional roles, most notably in certain forms of
memory. Conventional methods to look at adult neurogenesis are based on the
quantification of the number of newly born neurons using a simple cell counting
methodology. However, this type of approach fails to capture the dynamic aspects
of the neurogenic process, where neural proliferation, death and differentiation
take place continuously and simultaneously. In this paper, we propose a simple
mathematical approach to better understand the adult neurogenic process in the
hippocampus which in turn will allow for a better analysis of this process in
disease states and following drug therapies.
PMID- 26443688
TI - Dietary fatty acids and risk of hepatocellular carcinoma in the Singapore Chinese
health study.
AB - BACKGROUND & AIM: Lipidomic signature of lipid metabolism suggests that omega-6
polyunsaturated fatty acids (PUFA) may play a role in oncogenesis of
hepatocellular carcinoma (HCC). Hence, we examined the association between
dietary fatty acids and risk of HCC. METHODS: We used data from the Singapore
Chinese Health Study, a population-based prospective cohort of 63 257 Chinese men
and women aged 45-74 years enrolled between 1993 and 1998. Information on current
diet assessed via a validated semi-quantitative food frequency questionnaire,
medical history and lifestyle factors were obtained through in-person interview,
and incidence of HCC recorded through 31 Dec 2010. We also examined the
association between dietary fatty acids and HCC risk using a case-control set of
92 cases and 274 controls with available serological biomarkers of chronic
infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) nested within
this cohort. RESULTS: Among the dietary fat components examined, which included
saturated, monounsaturated, omega-3 and omega-6 PUFA, only omega-6 PUFA intake
displayed a dose-dependent, positive association with HCC risk (p for trend =
0.02). Compared to the lowest quartile, the hazard ratio for the highest quartile
intake was 1.49 [(95% confidence interval (CI):1.08-2.07)]. In the nested case
control study, only among individuals negative for serology markers of chronic
infection with HBV or HCV, those who consumed above median levels of dietary
omega-6 PUFA had increased HCC risk (odds ratio = 4.36, 95% CI = 1.59-11.94)
compared to those with lower intake. CONCLUSION: Dietary omega-6 PUFA may be
implicated in the risk of non-viral hepatitis related HCC.
PMID- 26443689
TI - Purification of a recombinant glutathione transferase from the causative agent of
hydatidosis, Echinococcus granulosus.
AB - This practical class activity was designed to introduce students to recombinant
protein expression and purification. The principal goal is to shed light on basic
aspects concerning recombinant protein production, in particular protein
expression, chromatography methods for protein purification, and enzyme activity
as a tool to evaluate purity and conformation of the recombinant product. Herein,
we describe the purification of a glutathione transferase from the human parasite
Echinococcus granulosus (EgGST1), the causative agent of hydatidosis. EgGST1 is
expressed fused to a histidine tag and is purified by immobilized metal affinity
chromatography. Protein quantification based on direct (UV absorbance) and
indirect (colorimetric) methods are used and discussed. A simple colorimetric
assay is used to measure GST activity and special emphasis is put on how to use
these measurements to follow protein purification yields, its enrichment and its
correct folding along the purification process. EgGST1 is easily expressed with
high yields, purified in absence of protease inhibitors and proved to be robust
concerning enzyme activity and protein integrity on a 1 week practical activity.
PMID- 26443690
TI - Prognostic significance of transaminases after acute ST-elevation myocardial
infarction: insights from a cardiac magnetic resonance study.
AB - BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI), the
relationship between transaminases and myocardial damage detected by cardiac
magnetic resonance (CMR) imaging is unknown and the prognostic value incompletely
investigated. MATERIALS AND METHODS: CMR imaging was performed in 167 STEMI
patients 2.3 [1.6-3.9] days after primary percutaneous coronary intervention
(PPCI). Blood samples for transaminase measurement (aspartate transaminase (AST)
and alanine transaminase (ALT)) were obtained serially from day 1 to day 4 after
PPCI. Patients were followed for major adverse cardiac events (MACE) for 2.7 [1.1
3.3] years. RESULTS: Admission and peak concentrations of AST and ALT were
significantly associated with ejection fraction (p < 0.001), infarct size (p <
0.001), and the presence of microvascular obstruction (p < 0.01). Peak values of
both transaminases showed a stronger correlation with CMR parameters than
admission values (all p < 0.05). In Kaplan-Meier analysis, a high peak AST or
high peak ALT was associated with reduced MACE-free survival (both p < 0.01),
whereas admission values were not (both p > 0.05). Peak AST (hazard ratio (HR):
4.93 [1.70-14.32], p = 0.003) and peak ALT (HR: 5.67 [1.94-16.56], p = 0.002)
were independent predictors of MACE after adjusting for clinical risk factors.
CONCLUSIONS: Transaminases measured in the acute phase after PPCI for STEMI are
associated with systolic dysfunction, more extensive myocardial necrosis and
microvascular injury with subsequent prognostic information on MACE at long-term
follow-up.
PMID- 26443691
TI - Towards scene adaptive image correspondence for placental vasculature mosaic in
computer assisted fetoscopic procedures.
AB - BACKGROUND: Visualization of the vast placental vasculature is crucial in
fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome
treatment. However, vasculature mosaic is challenging due to the fluctuating
imaging conditions during fetoscopic surgery. METHOD: A scene adaptive feature
based approach for image correspondence in free-hand endoscopic placental video
is proposed. It contributes towards existing techniques by introducing a failure
detection method based on statistical attributes of the feature distribution, and
an updating mechanism that self-tunes parameters to recover from registration
failures. RESULTS: Validations on endoscopic image sequences of a phantom and a
monkey placenta are carried out to demonstrate mismatch recovery. In two 100
frame sequences, automatic self-tuned results improved by 8% compared with manual
experience-based tuning and a slight 2.5% deterioration against exhaustive tuning
(gold standard). CONCLUSION: This scene-adaptive image correspondence approach,
which is not restricted to a set of generalized parameters, is suitable for
applications associated with dynamically changing imaging conditions. Copyright
(c) 2015 John Wiley & Sons, Ltd.
PMID- 26443693
TI - Examination of the Synthetic Control Method for Evaluating Health Policies with
Multiple Treated Units.
AB - This paper examines the synthetic control method in contrast to commonly used
difference-in-differences (DiD) estimation, in the context of a re-evaluation of
a pay-for-performance (P4P) initiative, the Advancing Quality scheme. The
synthetic control method aims to estimate treatment effects by constructing a
weighted combination of control units, which represents what the treated group
would have experienced in the absence of receiving the treatment. While DiD
estimation assumes that the effects of unobserved confounders are constant over
time, the synthetic control method allows for these effects to change over time,
by re-weighting the control group so that it has similar pre-intervention
characteristics to the treated group. We extend the synthetic control approach to
a setting of evaluation of a health policy where there are multiple treated
units. We re-analyse a recent study evaluating the effects of a hospital P4P
scheme on risk-adjusted hospital mortality. In contrast to the original DiD
analysis, the synthetic control method reports that, for the incentivised
conditions, the P4P scheme did not significantly reduce mortality and that there
is a statistically significant increase in mortality for non-incentivised
conditions. This result was robust to alternative specifications of the synthetic
control method. (c) 2015 The Authors. Health Economics published by John Wiley &
Sons Ltd.
PMID- 26443692
TI - Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding
proteins and cortisol in nonobese men and women: a randomized clinical trial.
AB - Young-onset calorie restriction (CR) in rodents decreases serum IGF-1
concentration and increases serum corticosterone levels, which have been
hypothesized to play major roles in mediating its anticancer and anti-aging
effects. However, little is known on the effects of CR on the IGF-1 system and
cortisol in humans. To test the sustained effects of CR on these key hormonal
adaptations, we performed a multicenter randomized trial of a 2-year 25% CR
intervention in 218 nonobese (body mass index between 22 and 27.8 kg m(-2) )
young and middle-aged (20-50 years age range) men and women. Average CR during
the first 6 months was 19.5 +/- 0.8% and 9.1 +/- 0.7% over the next 18 months of
the study. Weight loss averaged 7.6 +/- 0.3 kg over the 2-years period of which
71% was fat mass loss (P < 0.0001). Average CR during the CR caused a significant
21% increase in serum IGFBP-1 and a 42% reduction in IGF-1:IGFBP-1 ratio at 2
years (P < 0.008), but did not change IGF-1 and IGF-1:IGFBP-3 ratio levels. Serum
cortisol concentrations were slightly but significantly increased by CR at 1 year
only (P = 0.003). Calorie restriction had no effect on serum concentrations of
PDGF-AB and TGFbeta-1. We conclude, on the basis of the present and previous
findings, that, in contrast to rodents, humans do not respond to CR with a
decrease in serum IGF-1 concentration or with a sustained and biological relevant
increase in serum cortisol. However, long-term CR in humans significantly and
persistently increases serum IGFBP-1 concentration.
PMID- 26443694
TI - Robot-assisted laparoscopic resection of large retroperitoneal paraganglioma -
initial experience from China.
AB - BACKGROUND: There have been only four cases of robot-assisted laparoscopic
resection of retroperitoneal paraganglioma (PGL) in the literature. Here we
present our experience on robot-assisted laparoscopic resection of large PGL in
four patients to further evaluate its safety and efficacy. METHODS: From March
2013 to January 2015, four patients with large PGL underwent robot-assisted
laparoscopic resection. The tumors were located on the left side and adjacent to
the aorta. Patients' demographics, intraoperative and postoperative data were
collected, including intraoperative hemodynamic outcomes. RESULTS: In all cases,
the PGLs were successfully removed robotically without conversion to open surgery
and no intraoperative or postoperative complication occurred. The operative time
ranged from 58-113 min, and estimated blood loss ranged from 50-350 mL. There
were no significant intraoperative hemodynamic instabilities. The postoperative
hospital stay ranged from 4-6 days. CONCLUSIONS: With the advantages of robotic
system, robot-assisted resection of large retroperitoneal PGL is feasible, safe
and efficient. The robotic system has the potential to expand surgical treatment
modalities for complex PGL. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26443695
TI - Complication rate in adult deformity surgical treatment: safety of the posterior
osteotomies.
AB - PURPOSE: The treatment of adult scoliosis is a challenge especially in patients
over 50 years old with severe, rigid curves in whom the use of vertebral
osteotomies may be necessary to correct the deformity. The aim the study was to
analyse the perioperative complications related to vertebral osteotomies in
elderly treated for spinal deformity. METHODS: We analysed 72 consecutive cases
of kyphoscoliosis, we classify them according to Berjano-Lamartina
classification. We divided patients into two groups: we only practised SPO and/or
PO in patients that composed group A; we practised also PSO in patients that
composed group B. We retrospectively analysed the perioperative complications and
radiographical results. Average follow-up was 30 months. RESULTS: We had 50 cases
of degenerative segment diseases (DSD) Type III, 13 Type IVa DSD and 9 Type IVb
DSD. Mean age was 60.7 years old. Overall complication rate was 22.2 %. In group
A, the complication rate was 16.9 % while in group B it was 46.2 %. Mean Cobb
primary curve angle was 41.75 degrees with average C7 plumb line (C7PL) of 4.49
cm, residual scoliosis after surgery was 15.41 degrees and average C7PL of 2.08
cm, with statistically significant differences. CONCLUSIONS: Previous studies
have shown increased complication rates with vertebral osteotomies in elderly
patients, our experience support this evidence. Our study demonstrates a high
incidence of intraoperative complication rate in elderly patients underwent a
PSO. PSO is a demanding technique to be considered in very selected and motivated
patients who must be carefully informed about the risks of the procedure.
PMID- 26443696
TI - Effect of strength training with blood flow restriction on muscle power and
submaximal strength in eumenorrheic women.
AB - Blood flow restriction (BFR) training stimulates muscle size and strength by
increasing muscle activation, accumulation of metabolites and muscle swelling.
This method has been used in different populations, but no studies have evaluated
the effects of training on muscle power and submaximal strength (SS) in accounted
for the menstrual cycle. The aim of this study was to analyse the effect of
strength training (ST) with BFR on the muscle power and SS of upper and lower
limbs in eumenorrheic women. Forty untrained women (18-40 years) were divided
randomly and proportionally into four groups: (i) high-intensity ST at 80% of 1RM
(HI), (ii) low-intensity ST at 20% of 1RM combined with partial blood flow
restriction (LI + BFR), (iii) low-intensity ST at 20% of 1RM (LI) and d) control
group (CG). Each training group performed eight training sessions. Tests with a
medicine ball (MB), horizontal jump (HJ), vertical jump (VJ), biceps curls (BC)
and knee extension (KE) were performed during the 1st day follicular phase (FP),
14th day (ovulatory phase) and 26-28th days (luteal phase) of the menstrual
cycle. There was no significant difference among groups in terms of the MB, HJ,
VJ or BC results at any time point (P>0.05). SS in the KE exercise was
significantly greater in the LI + BFR group compared to the CG group (P = 0.014)
during the LP. Therefore, ST with BFR does not appear to improve the power of
upper and lower limbs and may be an alternative to improve the SS of lower limbs
of eumenorrheic women.
PMID- 26443697
TI - Operative Treatment of the Insertional Achilles Tendinopathy Through a
Transtendinous Approach.
AB - BACKGROUND: Different operative techniques have been proposed for the treatment
of insertional Achilles tendinopathy (IAT), with often disappointing results. The
aim of this study was to evaluate the outcome of the transtendinous approach in
IAT. METHODS: Forty patients operated with an IAT between 2010 and 2011 were
included in this retrospective study. The mean follow-up was 15.6 (+/-3.7, 12-27)
months. Indication for surgery was IAT with failed conservative therapy. Using a
transtendinous approach, the Achilles tendon (AT) was partially detached and all
pathologic tissues were debrided. The AT was reinserted using different anchor
techniques. Clinical data were recorded using examination and clinical scores
(American Orthopaedic Foot & Ankle Society [AOFAS], Foot and Ankle Outcome Score
[FAOS], Numerical Rating Scale [NRS], and Short Form-36 [SF-36]). RESULTS: The
mean AOFAS hindfoot score improved from 59.4 preoperatively to 86.5
postoperatively (P < .05). All FAOS subscales, NRS pain scores, and pain and
function subscales of SF-36 improved significantly. The median time of return to
work and sports was 14.5 (+/-17.6; 2-82) and 22.7 (+/-13.4; 7-58) weeks. Three
patients had superficial wound healing difficulties but required no revision. One
patient had to be revised due to a hematoma. Patients treated with 2 suture
anchors or double-row fixation technique improved significantly (P < .05)
compared to those with single anchor fixation, regarding AOFAS score (79.6 and
90.2) and FAOS subscale scores. Eighty-three percent of the patients showed good
to excellent results. CONCLUSION: The transtendinous approach allowed access to
all associated pathologies in IAT. It had relatively few complications and lead
to good clinical results. LEVEL OF CLINICAL EVIDENCE: Level IV, retrospective
case series.
PMID- 26443699
TI - Using motion parallax for laparoscopic surgery.
AB - BACKGROUND: In typical stereo display systems, the reproduced 3D scene is
distorted when the observer moves. Motion parallax is an important depth cue that
has the ability to correct this distortion. More importantly, motion parallax
enables the observer to look around objects to provide a better view. METHODS: A
robotically assisted laparoscope prototype was designed to provide motion
parallax. A study to adjust the camera-head mapping ratio (gain of motion
parallax) was performed. A series of phantom tests was conducted to test the
effectiveness of motion parallax. RESULTS: The experimental results showed that
the motion parallax was effective, and the gain of motion parallax was
subjective. For a regular laparoscope view distance, larger image zooming rates
required smaller gain; for the same equivalent image size, further observer
distance decreased the optimal gain. CONCLUSIONS: Motion parallax could be used
for improved visualization in laparoscopic surgery. Copyright (c) 2015 John Wiley
& Sons, Ltd.
PMID- 26443698
TI - Posterior Talar Shifting in Mobile-Bearing Total Ankle Replacement.
AB - BACKGROUND: End-stage ankle osteoarthritis frequently involves multiplanar
malalignment in both the coronal and the sagittal planes. Sagittal malalignment
often includes anterior translation of the talus relative to the tibia.
Restoration of the correct tibial and talar alignment is essential for the long
term survival of total ankle replacement. METHODS: This study includes 66
consecutive patients who underwent total ankle arthroplasty with the Hintegra
prosthesis from May 2011 to April 2014. There were 28 females (42.4%) and 38
males (57.6%) with a mean age of about 57 years (25-82 years). Patients were
clinically and radiologically assessed preoperatively and at 2, 6, and 12 months
postoperatively. RESULTS: At 12 months postoperatively, there was a statistically
significant increase in American Orthopaedic Foot & Ankle Society scores from
31.9 to 72.3. Range of motion significantly increased from 9.5 to 25.4 degrees.
In addition, there was a statistically significant decrease in visual analog
scale (VAS) pain score from 8.9 to 2.2. Furthermore, there was a significant
increase in the Tibio-Talar ratio from 2 to 6 months postoperatively (34.6%
37.2%). CONCLUSIONS: This study demonstrated significant improvements in clinical
and radiologic outcomes after Hintegra total ankle arthroplasty. Significant
movement of the talus occurs within the first 6 months postoperatively. This may
be the result of rebalancing of muscle and ligament forces after surgery. LEVEL
OF EVIDENCE: Level IV, case series.
PMID- 26443700
TI - Fixed ratio or lower limit of normal for the FEV1 /VC ratio: relation to symptoms
and extended lung function tests.
AB - There is no general agreement on the spirometric definition of chronic
obstructive pulmonary disease (COPD). The global initiative for obstructive lung
disease recommends a fixed ratio between forced expiratory volume in one-second
(FEV1 ) and forced vital capacity (FVC) of <0.7 (FR) for the diagnosis of COPD.
European Respiratory Society and American Thoracic Society favour the use of the
fifth percentile of the age-related FEV1 /FVC ratio (the lower limit of normal,
LLN). The purpose of this study was to analyse extensive lung function tests in
groups of subjects fulfilling none, either or both of the spirometric criteria
for COPD. From a previous population-based study, 450 subjects were examined with
spirometry, body pletysmography diffusing capacity for CO (DL,CO ), Impulse
Oscillometry System (IOS) and answered a questionnaire on respiratory symptoms
and diseases. Seventy subjects fulfilled both spirometric COPD criteria
(FR+LLN+), 62 subjects the fixed ratio criterion (FR+) only. Of the remaining 318
subjects, 236 were ever smokers (N-ES). Significant differences between all
groups were seen for FEV1 and DL,CO . Significant differences between groups were
also seen for residual volume (RV) and RV/total lung capacity. For IOS, variables
and symptoms increasingly abnormal values were seen from never smokers to
FR+LLN+. This study shows that subjects meeting both spirometric COPD criteria
frequently have symptoms and findings at extended lung function tests compatible
with the diagnosis. Also subjects meeting the fixed ratio criterion only tend to
have more symptoms and lung function findings compatible with COPD than ever
smoking subjects with FEV1 /VC > 0.7.
PMID- 26443701
TI - The rationale for deep brain stimulation in Alzheimer's disease.
AB - Alzheimer's disease is a major worldwide health problem with no effective
therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain
movement disorders and is increasingly being investigated for treatment of other
neural circuit disorders. Here we review the rationale for investigating DBS as a
therapy for Alzheimer's disease. Phase I clinical trials of DBS targeting memory
circuits in Alzheimer's disease patients have shown promising results in clinical
assessments of cognitive function, neurophysiological tests of cortical glucose
metabolism, and neuroanatomical volumetric measurements showing reduced rates of
atrophy. These findings have been supported by animal studies, where electrical
stimulation of multiple nodes within the memory circuit have shown
neuroplasticity through stimulation-enhanced hippocampal neurogenesis and
improved performance in memory tasks. The precise mechanisms by which DBS may
enhance memory and cognitive functions in Alzheimer's disease patients and the
degree of its clinical efficacy continue to be examined in ongoing clinical
trials.
PMID- 26443702
TI - Putting it all on pigmentation: Heuristics of a bold and stochastic cell fate
decision.
AB - Gradients of transmembrane potential coordinate cell-fate decisions and
patterning during embryogenesis and wound-healing. Bioelectrical signaling may
also be more important for adult pathologies than currently recognized. In this
issue of Science Signaling, Lobikin et al. describe a role for bioelectric
signals during the development of Xenopus leavis embryos to instruct an organism
level response reminiscent of neoplastic progression in melanoma.
PMID- 26443703
TI - Proteostasis trumps YAP in colon cancer.
AB - In this issue of Science Signaling, Zhang et al. find a new role for verteporfin
in the control of colorectal cancer progression through the selective induction
of proteotoxicity rather than through inhibition of the transcription cofactor
YAP. The study further documents the potential strategy of targeting proteostasis
to kill cancer cells.
PMID- 26443704
TI - The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both
egress of thymocytes from the thymus and lymphocyte motility.
AB - The serine and threonine kinase MST1 is the mammalian homolog of Hippo. MST1 is a
critical mediator of the migration, adhesion, and survival of T cells; however,
these functions of MST1 are independent of signaling by its typical effectors,
the kinase LATS and the transcriptional coactivator YAP. The kinase NDR1, a
member of the same family of kinases as LATS, functions as a tumor suppressor by
preventing T cell lymphomagenesis, which suggests that it may play a role in T
cell homeostasis. We generated and characterized mice with a T cell-specific
double knockout of Ndr1 and Ndr2 (Ndr DKO). Compared with control mice, Ndr DKO
mice exhibited a substantial reduction in the number of naive T cells in their
secondary lymphoid organs. Mature single-positive thymocytes accumulated in the
thymus in Ndr DKO mice. We also found that NDRs acted downstream of MST1 to
mediate the egress of mature thymocytes from the thymus, as well as the
interstitial migration of naive T cells within popliteal lymph nodes. Together,
our findings indicate that the kinases NDR1 and NDR2 function as downstream
effectors of MST1 to mediate thymocyte egress and T cell migration.
PMID- 26443706
TI - Serotonergic regulation of melanocyte conversion: A bioelectrically regulated
network for stochastic all-or-none hyperpigmentation.
AB - Experimentally induced depolarization of resting membrane potential in
"instructor cells" in Xenopus laevis embryos causes hyperpigmentation in an all
or-none fashion in some tadpoles due to excess proliferation and migration of
melanocytes. We showed that this stochastic process involved serotonin signaling,
adenosine 3',5'-monophosphate (cAMP), and the transcription factors cAMP response
element-binding protein (CREB), Sox10, and Slug. Transcriptional microarray
analysis of embryos taken at stage 15 (early neurula) and stage 45 (free-swimming
tadpole) revealed changes in the abundance of 45 and 517 transcripts,
respectively, between control embryos and embryos exposed to the instructor cell
depolarizing agent ivermectin. Bioinformatic analysis revealed that the human
homologs of some of the differentially regulated genes were associated with
cancer, consistent with the induced arborization and invasive behavior of
converted melanocytes. We identified a physiological circuit that uses
serotonergic signaling between instructor cells, melanotrope cells of the
pituitary, and melanocytes to control the proliferation, cell shape, and
migration properties of the pigment cell pool. To understand the stochasticity
and properties of this multiscale signaling system, we applied a computational
machine-learning method that iteratively explored network models to reverse
engineer a stochastic dynamic model that recapitulated the frequency of the all
or-none hyperpigmentation phenotype produced in response to various
pharmacological and molecular genetic manipulations. This computational approach
may provide insight into stochastic cellular decision-making that occurs during
normal development and pathological conditions, such as cancer.
PMID- 26443707
TI - A programme based on repeated hypoxia-hyperoxia exposure and light exercise
enhances performance in athletes with overtraining syndrome: a pilot study.
AB - Overtraining syndrome (OTS) is a major concern among endurance athletes and is a
leading cause in preventing them to perform for long periods. Intermittent
exposure to hypoxia has been shown to be an effective way of improving
performance without exercising. Aim of this pilot study was to evaluate
intermittent hypoxia-hyperoxia training combined with light exercise as an
intervention to facilitate athletes with OTS to restore their usual performance
level. Thirty-four track and field athletes were recruited: 15 athletes with OTS
volunteered to participate and undertook a conditioning programme consisting of
repeated exposures to hypoxia (O2 at 10%) and hyperoxia (O2 at 30%) (6-8 cycles,
total time 45 min-1 h), three times a week, delivered 1.5-2 h after a low
intensity exercise session (2 bouts of 30 min, running at 50% of VO2max with 10
min rest between bouts) over 4 weeks. Nineteen healthy track and field athletes
volunteered to participate as a control group and followed their usual training
schedule. Measurements before and after the intervention included exercise
capacity, analysis of heart rate variability and hematological parameters. In
athletes with OTS, a 4-week light exercise combined with intermittent hypoxia
hyperoxia training improved exercise performance (191.9 +/- 26.9 W versus 170.8
+/- 44.8 W in exercise capacity test, P = 0.01). Heart rate variability analysis
revealed an improved sympatho-parasympathetic index (low frequency/high frequency
ratio, 8.01 +/- 7.51 before and 1.45 +/- 1.71 after, P = 0.007). Hematological
parameters were unchanged. Our pilot study showed that intermittent hypoxia
hyperoxia training and low-intensity exercise can facilitate functional recovery
among athletes with OTS in a relatively short time.
PMID- 26443705
TI - Tumor-selective proteotoxicity of verteporfin inhibits colon cancer progression
independently of YAP1.
AB - Yes-associated protein 1 (YAP1) is a transcriptional coactivator in the Hippo
signaling pathway. Increased YAP1 activity promotes the growth of tumors,
including that of colorectal cancer (CRC). Verteporfin, a drug that enhances
phototherapy to treat neovascular macular degeneration, is an inhibitor of YAP1.
We found that verteporfin inhibited tumor growth independently of its effects on
YAP1 or the related protein TAZ in genetically or chemically induced mouse models
of CRC, in patient-derived xenografts, and in enteroid models of CRC. Instead,
verteporfin exhibited in vivo selectivity for killing tumor cells in part by
impairing the global clearance of high-molecular weight oligomerized proteins,
particularly p62 (a sequestrome involved in autophagy) and STAT3 (signal
transducer and activator of transcription 3; a transcription factor). Verteporfin
inhibited cytokine-induced STAT3 activity and cell proliferation and reduced the
viability of cultured CRC cells. Although verteporfin accumulated to a greater
extent in normal cells than in tumor cells in vivo, experiments with cultured
cells indicated that the normal cells efficiently cleared verteporfin-induced
protein oligomers through autophagic and proteasomal pathways. Culturing CRC
cells under hypoxic or nutrient-deprived conditions (modeling a typical CRC
microenvironment) impaired the clearance of protein oligomers and resulted in
cell death, whereas culturing cells under normoxic or glucose-replete conditions
protected cell viability and proliferation in the presence of verteporfin.
Furthermore, verteporfin suppressed the proliferation of other cancer cell lines
even in the absence of YAP1, suggesting that verteporfin may be effective against
multiple types of solid cancers.
PMID- 26443708
TI - Robot-assisted laparoscopic (RAL) procedures in general surgery.
AB - BACKGROUND: Robotics was introduced in clinical practice more than two decades
ago, and it has gained remarkable popularity for a wide variety of laparoscopic
procedures. We report our results of robot-assisted laparoscopic surgery (RALS)
in the most commonly applied general surgical procedures. METHOD: Ninety seven
patients underwent RALS from 2009 to 2012. Indications for RALS were
cholelithiasis, gastric carcinoma, splenic tumors, colorectal carcinoma, benign
colorectal diseases, non-toxic nodular goiter and incisional hernia. Records of
patients were analyzed for demographic features, intraoperative and postoperative
complications and conversion to open surgery. RESULTS: Forty six female and 51
male patients were operated and mean age was 58,4 (range: 25-88). Ninety three
out of 97 procedures (96%) were completed robotically, 4 were converted to open
surgery and there were 15 postoperative complications. There was no mortality.
CONCLUSION: Wide variety of procedures of general surgery can be managed safely
and effectively by RALS. Copyright (c) 2015 John Wiley & Sons, Ltd.
PMID- 26443710
TI - Ninety-six hours ordeal of priapism induced by paroxetine--A case report and
literature review.
AB - Priapism is a rare but severe medical condition of sustained and painful erection
of penis in the absence of any sexual stimulation, in which the penis does not
return to a flaccid state. It is considered to be a medical emergency because
without treatment it can lead to permanent damage and fibrosis of penis and in
the long run to impotency. Albeit that there is no uniform consensus regarding
the duration of sustained erection, an erection lasting more than 4 h is
generally considered as an emergency which needs immediate medical attention and
care. Priapism is commonly associated with iatrogenic, pharmacologic, underlying
medical, or traumatic causes. In this report, we present the case of a 42-year
old African American man who developed priapism after three weeks of therapy with
paroxetine which lasted for more than 96 h before coming to the attention of his
health-care providers. This case is unique in that there are no reports in
literature of an erection lasting for such a long duration following therapy with
paroxetine. The objective of this report is to highlight the importance of
recognizing the possibility of priapism with selective serotonin reuptake
inhibitors in general and paroxetine in particular since this condition is not
commonly seen in clinical practice to be associated with selective serotonin
reuptake inhibitors and may go unrecognized. Also, potential biological
mechanisms involved in the development of paroxetine-induced priapism are
presented.
PMID- 26443709
TI - Efficacy of four preventive measures against enamel demineralization at the
bracket periphery-comparison of microhardness and confocal laser microscopy
analysis.
AB - OBJECTIVES: The aim of this in-vitro study was to investigate the efficacy of
four preventive measures against enamel demineralization and to compare the
suitability of microhardness (MH) measurements and confocal laser microscopy
(CLSM). MATERIALS AND METHODS: A total of 80 teeth were randomly allocated into
four groups. The effect against demineralization of two coating materials (group
1: resin-modified glass ionomer (RMGI) cement varnish (ClinproXT); group 2:
composite sealant (ProSeal)) and that of two types of bracket-bonding material
(group 3: amorphous calcium phosphate (ACP) composite (AegisOrtho); group 4: RMGI
(FujiOrthoLC)) was compared after pH-cycling by MH and CLSM. Measurements were
made at the edge of the coating/bracket as well as at 50, 100, 200, and 400 MUm
distance. The data were converted into values of mineralization (Vol%) and
analyzed by parametric (ANOVA and Tukey's post hoc) or non-parametric (Kruskal
Wallis and Games-Howell post hoc) tests. RESULTS: ClinproXT and ProSeal were
proved to protect the bracket periphery. However, the area next to them showed
demineralizations. The mean area of lesion (CLSM-data) was significantly
different between the groups (p < 0.0001). The smallest lesions were revealed for
the RMGI-based materials. MH identified only for group 4 a significant difference
between the area next to the bracket base and that at 200 and 400 um distance.
CONCLUSION: There was nearly no lesion under both coatings. A stagnation of
demineralization was identified particularly for the RMGI. ProSeal showed an
inferior protection of the untreated enamel. MH and CLSM analysis were suitable
to detect subsurface lesions. CLINICAL RELEVANCE: A diverse efficacy of materials
against enamel demineralization at bracket periphery has to be noticed.
PMID- 26443711
TI - Effectiveness of long-acting risperidone in a patient with comorbid intellectual
disability, catatonic schizophrenia, and oneiroid syndrome.
AB - A patient with comorbid intellectual disability, catatonic schizophrenia, and
recurrent oneiroid state of consciousness improved on long-acting risperidone and
remains well at the three-year follow-up. We report a case treated with 50 mg
long-acting risperidone administered every 14 days, who has been followed-up for
three years. We studied his regional cerebral blood flow through technetium-99 m
hexamethylpropyleneamine oxime single-photon emission computed tomography after
two years of treatment. Symptoms of catatonic schizophrenia improved after two
months of treatment, followed suit by oneiroid syndrome remission. Two years
later, his brain perfusion was normal. No side effect has occurred since the
patient was started on long-acting risperidone. Long-acting risperidone proved to
be safe and effective in treating symptoms of catatonia and oneiroid syndrome.
PMID- 26443712
TI - Joint kinematics of surgeons during lumbar pedicle screw placement.
AB - BACKGROUND: A surgical robot for spine surgery has recently been developed. The
objective is to assess the joint kinematics of the surgeon during spine surgery.
METHODS: We enrolled 18 spine surgeons, who each performed pedicle screw
placement, and used an optoelectronic motion analysis system. Using three
dimensional (3D) motion images, distance changes in five joints and angle changes
in six joints were calculated during surgery. RESULTS: Distance fluctuations
increased gradually from the proximal to the distal joint. Angle fluctuations
were largest at the distal point but did not gradually increase, and the elbow
showed the second largest fluctuation. Changes along the X axis were larger than
those of the Y and Z axes. CONCLUSION: The distances gradually increased from
proximal portions of the body to the hand. In angle changes, the elbow was most
dynamic during pedicle screw placement. The surgeons' whole joints carry out a
harmonic role during lumbar pedicle screw placement. Copyright (c) 2015 John
Wiley & Sons, Ltd.
PMID- 26443713
TI - Superior vena cava syndrome due to isolated intrapulmonary Castleman's disease.
PMID- 26443714
TI - Intrauterine exposure to bisphenol A promotes different effects in both neonatal
and adult prostate of male and female gerbils (Meriones unguiculatus).
AB - Substances that mimic endogenous hormones may alter the cell signaling that
govern prostate development and predispose it to developing lesions in adult and
senile life. Bisphenol A is able to mimic estrogens, and studies have
demonstrated that low levels of exposure to this compound have caused alterations
during prostate development. The aim of this study was to describe the prostate
development in both male and female neonatal gerbils in normal conditions and
under exposure to BPA during intrauterine life, and also to analyze whether the
effects of intrauterine exposure to BPA remain in adulthood. Morphological,
stereological, three-dimensional reconstruction, and immunohistochemical methods
were employed. The results demonstrated that in 1-day-old normal gerbils, the
female paraurethral glands and the male ventral lobe are morphologically similar,
although its tissue components-epithelial buds (EB), periurethral mesenchyme
(PeM), paraurethral mesenchyme (PaM) or ventral mesenchymal pad (VMP), and smooth
muscle (SM)-have presented different immunolabeling pattern for androgen receptor
(AR), and for proliferating cell nuclear antigen (PCNA). Moreover, we observed a
differential response of male and female prostate to intrauterine BPA exposure.
In 1-day-old males, the intrauterine exposure to BPA caused a decrease of AR
positive cells in the PeM and SM, and a decrease of the proliferative status in
the EB. In contrast, no morphological alterations were observed in ventral
prostate of adult males. In 1-day-old females, BPA exposure promoted an increase
of estrogen receptor alpha (ERalpha) positive cells in PeM and PaM, a decrease of
AR-positive cells in EB and PeM, besides a reduction of cell proliferation in EB.
Additionally, the adult female prostate of BPA-exposed animals presented an
increase of AR- and PCNA-positive cells. These results suggest that the prostate
of female gerbils were more susceptible to the intrauterine BPA effects, since
they became more proliferative in adult life. (c) 2015 Wiley Periodicals, Inc.
Environ Toxicol 31: 1740-1750, 2016.
PMID- 26443715
TI - Epigenetics in Legg-Calve-Perthes disease: A study of global DNA methylation.
AB - OBJECTIVE: To examine the global methylation status of DNA in blood cells of
children with Legg-Calve-Perthes disease (LCPD), since the aetiopathogenesis of
LCPD remains unclear, and many factors closely associated with DNA methylation
may be linked to the occurrence of LCPD. METHODS: Children with LCPD and age-,
sex- and body mass index-matched controls were evaluated. Methylation levels of
the long interspersed nuclear element 1 (LINE-1), a biomarker of global DNA
methylation, were quantified by methylation-specific polymerase chain reaction.
RESULTS: Of 82 children with LCPD (68 male/14 female) and 120 matched controls
(98 male/22 female), methylation of the LINE-1 promoter was significantly lower
in patients with LCPD compared with controls. Subgroup analyses showed that
methylation of the LINE-1 promoter was significantly lower in male patients with
LCPD compared with male controls. No significant between-group differences were
observed in female participants. CONCLUSIONS: Reduced global DNA methylation may
be associated with increased risk of LCPD in male children. Further research is
required to understand whether detection of global DNA methylation may provide a
basis for clinical diagnosis and early intervention of LCPD.
PMID- 26443716
TI - Antenatal depression in coastal South India: Prevalence and risk factors in the
community.
AB - BACKGROUND: Antenatal depression is a highly prevalent disorder with serious
implications on maternal and child outcomes. There are few studies examining this
in low-middle-income community settings. AIMS: To determine the prevalence of
antenatal depression in women from a coastal rural background in Kerala and Tamil
Nadu and to determine its associated factors. MATERIALS AND METHODS: In this
cross-sectional community-based study, in 202 antenatal women, standard interview
and diagnostic criteria (Clinical Interview Schedule-Revised (CIS-R)) were
employed for identifying depression and examining a wide range of putative
clinical and sociocultural risk factors including domestic violence. RESULTS:
There was a 16.3% prevalence of depression among the 202 women sampled. The
possible risk factors after stepwise backward regression were pressure to have a
male child, 11.48 (2.36-55.78); financial difficulties, 8.23 (2.49-27.22); non
arranged marriage, 6.05 (1.72-21.23); history of miscarriage-still birth, 5.77
(1.55-21.43) and marital conflict, 9.55 (2.34-38.98). CONCLUSION: There is a need
to develop strategies for recognition and appropriate intervention for antenatal
depression, in the context of locally relevant risk factors, so as to improve
both maternal and child outcomes.
PMID- 26443717
TI - How Do Hospital Palliative Care Teams Use the WHO Guidelines to Manage Unrelieved
Cancer Pain? A 1-Year, Multicenter Audit in Japan.
AB - It has been reported that pain relief for patients with cancer is suboptimal in
Japan. This has been mainly attributed to inadequate dissemination of the World
Health Organization (WHO) guidelines for cancer pain management. To better
understand this problem, we reviewed how 6 hospital palliative care teams (HPCTs)
used the WHO guidelines for unrelieved pain in a 1-year audit that included 534
patients. The HPCT interventions were classified according to the contents of the
WHO guidelines. In our study, HPCT interventions involved opioid prescriptions in
>80% of referred patients, and "For the Individual" and "Attention to Detail"
were the 2 most important principles. Our study indicates which parts of the WHO
guidelines should be most heavily emphasized, when disseminating them in Japan.
PMID- 26443718
TI - Pediatrician Ambiguity in Understanding Palliative Sedation at the End of Life.
AB - CONTEXT: Palliative sedation is a means of relieving intractable symptoms at the
end of life, however, guidelines about its use lack consistency. In addition,
ethical concerns persist around the practice. There are reports of palliative
sedation in the pediatric literature, which highlight various institutional
perspectives. OBJECTIVES: This survey of 4786 pediatric providers sought to
describe their knowledge of and current practices around pediatric palliative
sedation. METHODS: Our survey was administered to pediatricians who care for
children at the end of life. The survey assessed agreement with a definition of
palliative sedation, as well as thoughts about its alignment with aggressive
symptom management. Bivariate analyses using chi2 and analysis of variance were
calculated to determine the relationship between responses to closed-ended
questions. Open-ended responses were thematically coded by the investigators and
reviewed for agreement. RESULTS: Nearly half (48.6%) of the respondents indicated
that the stated definition of palliative sedation "completely" reflected their
own views. Respondents were split when asked if they viewed any difference
between palliative sedation and aggressive symptom management: Yes (46%) versus
No (54%). Open-ended responses revealed specifics about the nature of variation
in interpretation. CONCLUSIONS: Responses point to ambiguity surrounding the
concept of palliative sedation. Pediatricians were concerned with a decreased
level of consciousness as the goal of palliative sedation. Respondents were split
on whether they view palliative sedation as a distinct entity or as one broad
continuum of care, equivalent to aggressive symptom management. Institutional
based policies are essential to clarify acceptable practice, enable open
communication, and promote further research.
PMID- 26443719
TI - Prevalence and Gender Differences of ODD, Anxiety, and Depression in a Sample of
Children With ADHD.
AB - OBJECTIVE: Studies on comorbidity in children diagnosed with ADHD have relied
more on parent/teacher reports instead of self-reported data and have focused on
the frequency of comorbid symptoms instead of scores above clinical cutoffs. The
purpose of this study was to examine the prevalence of oppositional defiant
disorder (ODD), anxiety, and depression in children with ADHD, using self-report
measures for internalizing symptoms and parent-reported measures for
externalizing symptoms for increased accuracy. Gender differences were also
assessed. METHOD: Parents of 197 children diagnosed with ADHD answered the
Disruptive Behavior Rating Scale, and 112 of the children filled out the
Multidimensional Anxiety Scale for Children and the Children's Depression
Inventory. RESULTS: Results revealed that 19.28% of the children met cut-off
criteria for ODD, 41.96% for anxiety, and 21.43% for depression. CONCLUSION: Our
findings indicate a relatively lower prevalence of ODD and a slightly higher
prevalence of anxiety symptoms than previously reported. Possible explanations
and future directions are discussed.
PMID- 26443720
TI - Radiation-Induced Thyroid Cancer: Gender-Related Disease Characteristics and
Survival.
AB - BACKGROUND: Radiation exposure is a well-known risk factor for well
differentiated thyroid cancer (WDTC). However, gender disparity in disease
characteristics is not completely understood. The purpose of this study was to
determine the behavior of radiation-induced thyroid cancer according to gender.
METHODS: Charts of all patients diagnosed with WDTC after radiation exposure
between the years 1985 and 2013 in a tertiary referral center were retrieved.
RESULTS: Forty-three patients were reviewed, 29 females and 14 males. Mean age of
exposure for women and men were 17.1 +/- 19.5 and 15.5 +/- 12.5 years,
respectively (P = .78). Age at diagnosis were 47.5 +/- 15.5 and 41.5 +/- 15 years
for women and men, respectively (P = .18). Mean disease-specific survival was
44.1 and 43.7 years for women and men, respectively (P = .50). CONCLUSIONS:
Similar disease characteristics, tumor pathology, disease-free survival, and
overall survival in both genders. In sporadic well-differentiated thyroid
carcinoma, female gender is associated with better tumor behavior and prognosis.
However, our results suggest that women are more affected by radiation than men
and therefore have the same prognosis as men.
PMID- 26443721
TI - The P2RY2 Receptor Induces Carcinoma Cell Migration and EMT Through Cross-Talk
With Epidermal Growth Factor Receptor.
AB - Extracellular nucleotides are signaling elements present in the tumor
microenvironment; however, their role in tumor growth is not completely
understood. In the present study, we asked whether nucleotides regulate cell
migration in ovarian carcinoma-derived cells. We observed that 100 MUM UTP
induced migration in SKOV-3 cells (1.57 +/- 0.08 fold over basal), and RT-PCR
showed expression of transcripts for the P2RY2 and P2RY4 receptors. Knockdown of
P2RY2 expression in SKOV-3 cells (P2RY2-KD) abolished the UTP-induced migration.
The mechanism activated by UTP to induce migration involves transactivation of
the epidermal growth factor receptor (EGFR) since we observed that the EGFR
kinase inhibitor AG1478 and the PI3K inhibitor Wortmannin inhibit this response
(to 0.76 +/- 0.23 and 0.46 +/- 0.14 relative to the control, respectively). In
agreement with these observations, UTP was able to modify the phosphorylation
state of the EGFR; likewise, the induction of ERK1/2 phosphorylation promoted by
UTP was abolished by a 30-60 min treatment with AG1478. Our data also suggested
that the enhanced cell migration involves the epithelium to mesenchymal
transition (EMT) process, since a 12 h stimulation of SKOV-3 cells with 100 MUM
UTP showed an increase in vimentin and SNAIL protein levels (459.8 +/- 132.4%
over basal for SNAIL). Interestingly, treatment with apyrase (10 U/mL) reduces
the migration of control cells and induces a considerable enrichment of E
cadherin in the cell-cell contacts, favoring an epithelial phenotype and strongly
suggesting that the nucleotides released by tumor cells and acting through the
P2RY2 receptor are potential regulators of invasiveness.
PMID- 26443723
TI - Magnesium Transport and Magnesium Homeostasis.
AB - This review reviews the properties and regulation of the Salmonella enterica
serovar Typhimurium and Escherichia coli transporters that mediate Mg2+ influx:
CorA and the Mgt P-type ATPases. In addition, potential Mg2+ regulation of
transcription and translation, largely via the PhoPQ two component system, is
discussed. CorA proteins are a unique class of transporters and are widespread in
the Bacteria and Archaea, with rather distant but functional homologs in
eukaryotes. The Mgt transporters are highly homologous to other P-type ATPases
but are more closely related to the eukaryotic H+ and Ca2+ ATPases than to most
prokaryotic ATPases. Hundreds of homologs of CorA are currently known from
genomic sequencing. In contrast, only when extracellular and possibly
intracellular Mg2+ levels fall significantly is the expression of mgtA and mgtB
induced. Topology studies using blaM and lacZ fusions initially indicated that
the Salmonella serovar Typhimurium CorA contained three transmembrane (TM)
segments; however, subsequent data obtained using a variety of approaches showed
that the CorA superfamily of proteins have only two TMs at the extreme C
terminus. PhoP-PhoQ is a two-component system consisting of PhoQ, the
sensor/receptor histidine kinase, and PhoP, the response
regulator/transcriptional activator. The expression of both mgtA and mgtCB in
either E. coli or Salmonella serovar Typhimurium is markedly induced in a PhoPQ
dependent manner by low concentrations of Mg2+ in the medium. phoP and phoQ form
an operon with two promoters in both E. coli and Salmonella serovar Typhimurium.
PMID- 26443724
TI - Undecaprenyl Phosphate Synthesis.
AB - Undecaprenyl phosphate (C55-P) is an essential 55-carbon long-chain isoprene
lipidinvolved in the biogenesis of bacterial cell wall carbohydrate polymers:
peptidoglycan, O antigen, teichoic acids, and other cell surface polymers. It
functions as a lipid carrier that allows the traffic of sugar intermediates
across the plasma membrane, towards the periplasm,where the polymerization of the
different cellwall components occurs. At the end of these processes, the lipid is
released in a pyrophosphate form (C55-PP). C55-P arises from the
dephosphorylation of C55-PP, which itself originates from either a recycling
event or a de novo synthesis. In Escherichia coli, the formation of C55-PP is
catalyzed by the essential UppS synthase, a soluble cis-prenyltransferase,
whichadds eight isoprene units ontofarnesyl pyrophosphate. Severalapo- and halo
UppSthree-dimensional structures have provided a high level of understanding of
this enzymatic step. The following dephosphorylationstep is required before the
lipid carrier can accept a sugar unit at the cytoplasmic face of the membrane.
Four integralmembrane proteins have been shown to catalyzethis reaction in E.
coli:BacA and three members of the PAP2 super-family:YbjG, LpxT, and PgpB. None
of these enzymes is essential,but the simultaneous inactivation of bacA, ybjG,
and pgpB genes gave rise to a lethal phenotype, raising the question of the
relevance of such a redundancy of activity. It was alsorecently shown that
LpxTcatalyzes the specific transfer of the phosphate group arising from C55-PP to
the lipidA moiety of lipopolysaccharides, leading to a lipid-A 1-diphosphate form
whichaccounts for one-third of the total lipidA in wild-type E. coli cells. The
active sites of LpxT, PgpB,andYbjG were shown to face the periplasm, suggesting
that PAP2 enzymes arerather involved in C55-PP recycling. These recent
discoveries have opened the way to the elucidation of the functional and
structural characterization of these different phosphatases.
PMID- 26443725
TI - Antibiotic Resistance Mechanisms, with an Emphasis on Those Related to the
Ribosome.
AB - Antibiotic resistance is a fundamental aspect of microbiology, but it is also a
phenomenon of vital importance in the treatment of diseases caused by pathogenic
microorganisms. A resistance mechanism can involve an inherent trait or the
acquisition of a new characteristic through either mutation or horizontal gene
transfer. The natural susceptibilities of bacteria to a certain drug vary
significantly from one species of bacteria to another and even from one strain to
another. Once inside the cell, most antibiotics affect all bacteria similarly.
The ribosome is a major site of antibiotic action and is targeted by a large and
chemically diverse group of antibiotics. A number of these antibiotics have
important applications in human and veterinary medicine in the treatment of
bacterial infections. The antibiotic binding sites are clustered at functional
centers of the ribosome, such as the decoding center, the peptidyl transferase
center, the GTPase center, the peptide exit tunnel, and the subunit interface
spanning both subunits on the ribosome. Upon binding, the drugs interfere with
the positioning and movement of substrates, products, and ribosomal components
that are essential for protein synthesis. Ribosomal antibiotic resistance is due
to the alteration of the antibiotic binding sites through either mutation or
methylation. Our knowledge of antibiotic resistance mechanisms has increased, in
particular due to the elucidation of the detailed structures of antibiotic
ribosome complexes and the components of the efflux systems. A number of
mutations and methyltransferases conferring antibiotic resistance have been
characterized. These developments are important for understanding and approaching
the problems associated with antibiotic resistance, including design of
antimicrobials that are impervious to known bacterial resistance mechanisms.
PMID- 26443726
TI - Peptidoglycan Recycling.
AB - Peptidoglycan (PG) recycling allows Escherichia coli to reuse the massive amounts
of sacculus components that are released during elongation. Goodell and Schwarz,
in 1985, labeled E. coli cells with 3H-diaminopimelic acid (DAP) and chased.
During the chase, the DAP pool dropped dramatically, whereas the precursor pool
dropped only slightly. This could only occur if DAP from the sacculi was being
used to produce more precursor. They calculated that the cells were recycling
about 45% of their wall DAP (actually, 60% of the side walls, since the poles are
stable). Thus, recycling was discovered. Goodell went on to show that the
tripeptide, L-Ala-D-Glu-DAP, could be taken up via opp and used directly to form
PG. It was subsequently shown that uptake was predominantly via a permease, AmpG,
that was specific for GlcNAc-anhMurNAc with attached peptides. Eleven genes have
been identified which appear to have as their sole function the recovery of
degradation products from PG. PG represents only 2.5% of the cell mass, so the
reason for this investment in recycling is obscure. Recycling enzymes exist that
are specific for every bond in the principal product taken up by AmpG, namely,
GlcNAc-anh-MurNAc-tetrapeptide. However, most of the tripeptide, L-Ala-D-Glu-DAP,
is used by murein peptide ligase (Mpl) to form the precursor intermediate UDP
MurNAc-tripeptide. anh-MurNAc can be converted to GlcNAc by a two-step process
and thus is available for use. Surprisingly, in the absence of AmpD, an enzyme
that cleaves the anh-MurNAc-L-Ala bond, anh-MurNAc-tripeptide accumulates,
resulting in induction of beta-lactamase. However, this has nothing to do with
the induction of beta-lactamase by beta-lactam antibiotics. Uehara, Suefuji, and
Park (unpublished data) have some evidence suggesting that murein pentapeptide
may be involved. The presence of orthologs suggests that recycling also exists in
many Gram-negative bacteria. Surprisingly, the ortholog search also revealed that
all mammals may have an AmpG ortholog! Hence, mammalian AmpG may be involved in
the process of innate immunity.
PMID- 26443722
TI - Protein and small non-coding RNA-enriched extracellular vesicles are released by
the pathogenic blood fluke Schistosoma mansoni.
AB - BACKGROUND: Penetration of skin, migration through tissues and establishment of
long-lived intravascular partners require Schistosoma parasites to successfully
manipulate definitive host defences. While previous studies of larval
schistosomula have postulated a function for excreted/secreted (E/S) products in
initiating these host-modulatory events, the role of extracellular vesicles (EVs)
has yet to be considered. Here, using preparatory ultracentrifugation as well as
methodologies to globally analyse both proteins and small non-coding RNAs
(sncRNAs), we conducted the first characterization of Schistosoma mansoni
schistosomula EVs and their potential host-regulatory cargos. RESULTS:
Transmission electron microscopy analysis of EVs isolated from schistosomula in
vitro cultures revealed the presence of numerous, 30-100 nm sized exosome-like
vesicles. Proteomic analysis of these vesicles revealed a core set of 109
proteins, including homologs to those previously found enriched in other
eukaryotic EVs, as well as hypothetical proteins of high abundance and currently
unknown function. Characterization of E/S sncRNAs found within and outside of
schistosomula EVs additionally identified the presence of potential gene
regulatory miRNAs (35 known and 170 potentially novel miRNAs) and tRNA-derived
small RNAs (tsRNAs; nineteen 5' tsRNAs and fourteen 3' tsRNAs). CONCLUSIONS: The
identification of S. mansoni EVs and the combinatorial protein/sncRNA
characterization of their cargo signifies that an important new participant in
the complex biology underpinning schistosome/host interactions has now been
discovered. Further work defining the role of these schistosomula EVs and the
function/stability of intra- and extra-vesicular sncRNA components presents
tremendous opportunities for developing novel schistosomiasis diagnostics or
interventions.
PMID- 26443727
TI - Modification of the Ribosome and the Translational Machinery during Reduced
Growth Due to Environmental Stress.
AB - Escherichia coli strains normally used under laboratory conditions have been
selected for maximum growth rates and require maximum translation efficiency.
Recent studies have shed light on the structural and functional changes undergone
by the translational machinery in E. coli during heat and cold shock and upon
entry into stationary phase. In these situations both the composition and the
partitioning of this machinery into the different pools of cellular ribosomes are
modified. As a result, the translational capacity of the cell is dramatically
altered. This review provides a comprehensive account of these modifications,
regardless of whether or not their underlying mechanisms and their effects on
cellular physiology are known. Not only is the composition of the ribosome
modified upon entry into stationary phase, but the modification of other
components of the translational machinery, such as elongation factor Tu (EFTu)
and tRNAs, has also been observed. Hibernation-promoting factor (HPF), paralog
protein Y (PY), and ribosome modulation factor (RMF) may also be related to the
general protection against environmental stress observed in stationary-phase E.
coli cells, a role that would not be revealed necessarily by the viability
assays. Even for the best-characterized ribosome-associated factors induced under
stress (RMF, PY, and initiation factors), we are far from a complete
understanding of their modes of action.
PMID- 26443728
TI - Biosynthesis and Use of Cobalamin (B12).
AB - This review summarizes research performed over the last 23 years on the genetics,
enzyme structures and functions, and regulation of the expression of the genes
encoding functions involved in adenosylcobalamin (AdoCbl, or coenzyme B12)
biosynthesis. It also discusses the role of coenzyme B12 in the physiology of
Salmonella enterica serovar Typhimurium LT2 and Escherichia coli. John Roth's
seminal contributions to the field of coenzyme B12 biosynthesis research brought
the power of classical and molecular genetic, biochemical, and structural
approaches to bear on the extremely challenging problem of dissecting the steps
of what has turned out to be one of the most complex biosynthetic pathways known.
In E. coli and serovar Typhimurium, uro'gen III represents the first branch point
in the pathway, where the routes for cobalamin and siroheme synthesis diverge
from that for heme synthesis. The cobalamin biosynthetic pathway in P.
denitrificans was the first to be elucidated, but it was soon realized that there
are at least two routes for cobalamin biosynthesis, representing aerobic and
anaerobic variations. The expression of the AdoCbl biosynthetic operon is complex
and is modulated at different levels. At the transcriptional level, a sensor
response regulator protein activates the transcription of the operon in response
to 1,2-Pdl in the environment. Serovar Typhimurium and E. coli use ethanolamine
as a source of carbon, nitrogen, and energy. In addition, and unlike E. coli,
serovar Typhimurium can also grow on 1,2-Pdl as the sole source of carbon and
energy.
PMID- 26443729
TI - Amino Acid Metabolism and Fluxes.
AB - By the mid1960s, the pioneering work of Umbarger and Gerhart and Pardee had shown
us that carbon flow through a biosynthetic pathway was controlled by allosteric
inhibition of the first enzyme of the pathway by its end product; and, studies of
the lac operon by Jacob and Monod had established that genes were controlled by
an operator-repressor mechanism. During the intervening forty-plus years,
knowledge and technologies have continued to explode in unanticipated ways.
Today, we understand in great detail the molecular mechanisms of the many levels
of metabolic and genetic regulation that control carbon flow through the amino
acid biosynthetic pathways. Traditional experimental approaches are not
sufficient for the integration and reconstruction of complex biological systems
using data mostly generated by high-throughput experiments. Only with
computational methods and adequate modeling tools will we be able to reconstruct
and query these large and complicated systems. Due to complicated enzyme reaction
mechanisms and the frequent lack of rate constant measurements needed for solving
differential equations, most investigators have turned their attention to the
development of abstract, top-down modeling tools. For example, Palsson and
colleagues have used metabolic flux balance analysis (FBA) methods to simulate
steady-state metabolite flux through E. coli pathways representing hundreds of
enzyme steps. Recently, Yang et al. have developed a bottom-up, enzyme mechanism
modeling language, kMech (kinetic mechanism), for the mathematical simulation of
metabolic pathways.
PMID- 26443730
TI - Nus Factors of Escherichia coli.
AB - The Nus factors-NusA, NusB, NusE, and NusG-area set of well-conserved proteins in
bacteria and are involved in transcription elongation, termination,
antitermination, and translation processes. Originally, Escherichia coli host
mutations defective for supporting bacteriophage lambda N-mediated
antitermination were mapped to the nusA (nusA1), nusB (nusB5, nusB101), and nusE
(nusE71) genes, and hence, these genes were named nus for Nutilization substances
(Nus). Subsequently,the Nus factors were purified and their roles in different
host functions were elucidated. Except for NusB, deletion of which is
conditionally lethal, all the other Nus factors are essential for E. coli. Among
the Nus factors, NusA has the most varied functions. It specifically binds to RNA
polymerase (RNAP), nascent RNA, and antiterminator proteins like N and Q and
hence takes part in modulating transcription elongation, termination, and
antitermination. It is also involved in DNA repair pathways. NusG interacts with
RNAP and the transcription termination factor Rho and therefore is involved in
both factor-dependent termination and transcription elongation processes. NusB
and NusE are mostly important in antitermination at the ribosomal operon
transcription. NusE is a component of ribosome and may take part in facilitating
the coupling between transcription and translation. This chapter emphasizes the
structure-function relationship of these factors and their involvement in
different fundamental cellular processes from a mechanistic angle.
PMID- 26443731
TI - Respiration of Nitrate and Nitrite.
AB - Nitrate reduction to ammonia via nitrite occurs widely as an anabolic process
through which bacteria, archaea, and plants can assimilate nitrate into cellular
biomass. Escherichia coli and related enteric bacteria can couple the eight
electron reduction of nitrate to ammonium to growth by coupling the nitrate and
nitrite reductases involved to energy-conserving respiratory electron transport
systems. In global terms, the respiratory reduction of nitrate to ammonium
dominates nitrate and nitrite reduction in many electron-rich environments such
as anoxic marine sediments and sulfide-rich thermal vents, the human
gastrointestinal tract, and the bodies of warm-blooded animals. This review
reviews the regulation and enzymology of this process in E. coli and, where
relevant detail is available, also in Salmonella and draws comparisons with and
implications for the process in other bacteria where it is pertinent to do so.
Fatty acids may be present in high levels in many of the natural environments of
E. coli and Salmonella in which oxygen is limited but nitrate is available to
support respiration. In E. coli, nitrate reduction in the periplasm involves the
products of two seven-gene operons, napFDAGHBC, encoding the periplasmic nitrate
reductase, and nrfABCDEFG, encoding the periplasmic nitrite reductase. No
bacterium has yet been shown to couple a periplasmic nitrate reductase solely to
the cytoplasmic nitrite reductase NirB. The cytoplasmic pathway for nitrate
reduction to ammonia is restricted almost exclusively to a few groups of
facultative anaerobic bacteria that encounter high concentrations of
environmental nitrate.
PMID- 26443732
TI - Assembly of the 30S Ribosomal Subunit.
AB - Protein synthesis involves nearly a third of the total molecules in a typical
bacterial cell. Within the cell, protein synthesis is performed by the ribosomes,
and research over several decades has investigated ribosomal formation,
structure, and function. This review provides an overview of the current
understanding of the assembly of the Escherichia coli 30S ribosomal subunit. The
E. coli 30S subunit contains one rRNA molecule (16S) and 21 ribosomal proteins (r
proteins; S1 to S21). The formation of functional subunits can occur as a self
assembly process in vitro; i.e., all the information required for the formation
of active ribosomes resides in the primary sequences of the r-proteins and rRNAs.
In vitro reconstitution of functional 30S subunits is carried out by using a
mixture of TP30, individually purified natural or recombinant r-proteins, and
natural 16S rRNA. Chemical probing and primer extension analysis have been used
extensively to monitor changes in the reactivities of nucleotides in 16S rRNA
during the in vitro reconstitution of 30S subunits. The potential roles for r
proteins in 30S subunit assembly were determined by omitting single proteins in
reconstitution experiments. The RNPs resulting from single protein omissions were
examined in terms of their composition and function to determine the roles of the
absent proteins. Recent developments in understanding the structure of the 30S
subunit have led to speculation about roles for some of the r-proteins in
assembly. The crystal structures of the 30S subunit (1, 2) and the 70S ribosome
(3) reveal details of the r-protein and rRNA interactions.
PMID- 26443733
TI - The Cold Shock Response.
AB - This review focuses on the cold shock response of Escherichia coli. Change in
temperature is one of the most common stresses that an organism encounters in
nature. Temperature downshift affects the cell on various levels: (i) decrease in
the membrane fluidity; (ii) stabilization of the secondary structures of RNA and
DNA; (iii) slow or inefficient protein folding; (iv) reduced ribosome function,
affecting translation of non-cold shock proteins; (v) increased negative
supercoiling of DNA; and (vi) accumulation of various sugars. Cold shock proteins
and certain sugars play a key role in dealing with the initial detrimental effect
of cold shock and maintaining the continued growth of the organism at low
temperature. CspA is the major cold shock protein of E. coli, and its homologues
are found to be widespread among bacteria, including psychrophilic,
psychrotrophic, mesophilic, and thermophilic bacteria, but are not found in
archaea or cyanobacteria. Significant, albeit transient, stabilization of the
cspA mRNA immediately following temperature downshift is mainly responsible for
its cold shock induction. Various approaches were used in studies to detect cold
shock induction of cspA mRNA. Sugars are shown to confer protection to cells
undergoing cold shock. The study of the cold shock response has implications in
basic and health-related research as well as in commercial applications. The cold
shock response is elicited by all types of bacteria and affects these bacteria at
various levels, such as cell membrane, transcription, translation, and
metabolism.
PMID- 26443734
TI - Nucleotides, Nucleosides, and Nucleobases.
AB - We review literature on the metabolism of ribo- and deoxyribonucleotides,
nucleosides, and nucleobases in Escherichia coli and Salmonella,including
biosynthesis, degradation, interconversion, and transport. Emphasis is placed on
enzymology and regulation of the pathways, at both the level of gene expression
and the control of enzyme activity. The paper begins with an overview of the
reactions that form and break the N-glycosyl bond, which binds the nucleobase to
the ribosyl moiety in nucleotides and nucleosides, and the enzymes involved in
the interconversion of the different phosphorylated states of the nucleotides.
Next, the de novo pathways for purine and pyrimidine nucleotide biosynthesis are
discussed in detail.Finally, the conversion of nucleosides and nucleobases to
nucleotides, i.e.,the salvage reactions, are described. The formation of
deoxyribonucleotides is discussed, with emphasis on ribonucleotidereductase and
pathways involved in fomation of dUMP. At the end, we discuss transport systems
for nucleosides and nucleobases and also pathways for breakdown of the
nucleobases.
PMID- 26443735
TI - From Iron and Cysteine to Iron-Sulfur Clusters: the Biogenesis Protein
Machineries.
AB - This review describes the two main systems, namely the Isc (iron-sulfur cluster)
and Suf (sulfur assimilation) systems, utilized by Escherichia coli and
Salmonella for the biosynthesis of iron-sulfur (Fe-S) clusters, as well as other
proteins presumably participating in this process. In the case of Fe-S cluster
biosynthesis, it is assumed that the sulfur atoms from the cysteine desulfurase
end up at cysteine residues of the scaffold protein, presumably waiting for iron
atoms for cluster assembly. The review discusses the various potential iron donor
proteins. For in vitro experiments, in general, ferrous salts are used during the
assembly of Fe-S clusters, even though this approach is unlikely to reflect the
physiological conditions. The fact that sulfur atoms can be directly transferred
from cysteine desulfurases to scaffold proteins supports a mechanism in which the
latter bind sulfur atoms first and iron atoms afterwards. In E. coli, fdx gene
inactivation results in a reduced growth rate and reduced Fe-S enzyme activities.
Interestingly, the SufE structure resembles that of IscU, strengthening the
notion that the two proteins share the property of acting as acceptors of sulfur
atoms provided by cysteine desulfurases. Several other factors have been
suggested to participate in cluster assembly and repair in E. coli and
Salmonella. Most of them were identified by their abilities to act as extragenic
and/or multicopy suppressors of mutations in Fe-S cluster metabolism, while
others possess biochemical properties that are consistent with a role in Fe-S
cluster biogenesis.
PMID- 26443736
TI - The Aerobic and Anaerobic Respiratory Chain of Escherichia coli and Salmonella
enterica: Enzymes and Energetics.
AB - Escherichia coli contains a versatile respiratory chain which oxidizes ten
different electron donor substrates and transfers the electrons to terminal
reductases or oxidases for the reduction of six different electron acceptors.
Salmonella is able to use even two more electron acceptors. The variation is
further increased by the presence of isoenzymes for some substrates. Various
respiratory pathways can be established by combining the oxidation of different
electron donors and acceptors which are linked by respiratory quinones. The
enzymes vary largely with respect to architecture, membrane topology, and mode of
energy conservation. Most of the energy-conserving dehydrogenases (e.g., FdnGHI,
HyaABC, and HybCOAB) and of the terminal reductases (CydAB, NarGHI, and others)
form a proton potential (Deltap) by a redox loop mechanism. Only two enzymes
(NuoA-N and CyoABCD) couple the redox energy to proton translocation by proton
pumping. A large number of dehydrogenases (e.g., Ndh, SdhABCD, and GlpD) and of
terminal reductases (e.g., FrdABCD and DmsABC) do not conserve the redox energy
in a proton potential. For most of the respiratory enzymes, the mechanism of
proton potential generation is known from structural and biochemical studies or
can be predicted from sequence information. The H+/2e- ratios of proton
translocation for most respiratory chains are in the range from 2 to 6 H+/2e-.
The energetics of the individual redox reactions and of the respiratory chains is
described. In contrast to the knowledge on enzyme function are physiological
aspects of respiration such as organization and coordination of the electron
transport and the use of alternative respiratory enzymes, not well characterized.
PMID- 26443737
TI - Biotin and Lipoic Acid: Synthesis, Attachment, and Regulation.
AB - Two vitamins, biotin and lipoic acid, are essential in all three domains of life.
Both coenzymes function only when covalently attached to key metabolic enzymes.
There they act as "swinging arms" that shuttle intermediates between two active
sites (= covalent substrate channeling) of key metabolic enzymes. Although biotin
was discovered over 100 years ago and lipoic acid was discovered 60 years ago, it
was not known how either coenzyme is made until recently. In Escherichia coli the
synthetic pathways for both coenzymes have now been worked out for the first
time. The late steps of biotin synthesis, those involved in assembling the fused
rings, were well described biochemically years ago, although recent progress has
been made on the BioB reaction, the last step of the pathway, in which the biotin
sulfur moiety is inserted. In contrast, the early steps of biotin synthesis,
assembly of the fatty acid-like "arm" of biotin, were unknown. It has now been
demonstrated that the arm is made by using disguised substrates to gain entry
into the fatty acid synthesis pathway followed by removal of the disguise when
the proper chain length is attained. The BioC methyltransferase is responsible
for introducing the disguise and the BioH esterase for its removal. In contrast
to biotin, which is attached to its cognate proteins as a finished molecule,
lipoic acid is assembled on its cognate proteins. An octanoyl moiety is
transferred from the octanoyl-ACP of fatty acid synthesis to a specific lysine
residue of a cognate protein by the LipB octanoyl transferase, followed by sulfur
insertion at carbons C6 and C8 by the LipA lipoyl synthetase. Assembly on the
cognate proteins regulates the amount of lipoic acid synthesized, and thus there
is no transcriptional control of the synthetic genes. In contrast,
transcriptional control of the biotin synthetic genes is wielded by a remarkably
sophisticated, yet simple, system exerted through BirA, a dual-function protein
that both represses biotin operon transcription and ligates biotin to its cognate
protein.
PMID- 26443738
TI - The SOS Regulatory Network.
AB - All organisms possess a diverse set of genetic programs that are used to alter
cellular physiology in response to environmental cues. The gram-negative
bacterium Escherichia coli induces a gene regulatory network known as the "SOS
response" following exposure to DNA damage, replication fork arrest, and a myriad
of other environmental stresses. For over 50 years, E. coli has served as the
paradigm for our understanding of the transcriptional and physiological changes
that occur after DNA damage. In this chapter, we summarize the current view of
the SOS response and discuss how this genetic circuit is regulated. In addition
to examining the E. coli SOS response, we include a discussion of the SOS
regulatory networks found in other bacteria to provide a broad perspective on the
mechanism and diverse physiological responses that ensueto protect cells and
maintain genome integrity.
PMID- 26443739
TI - Biosynthesis and Insertion of the Molybdenum Cofactor.
AB - The transition element molybdenum (Mo) is of primordial importance for biological
systems as it is required by enzymes catalyzing key reactions in global carbon,
sulfur, and nitrogen metabolism. In order to gain biological activity, Mo has to
be complexed by a special cofactor. With the exception of bacterial nitrogenase,
all Mo-dependent enzymes contain a unique pyranopterin-based cofactor
coordinating a Mo atom at their catalytic site. Various types of reactions are
catalyzed by Mo enzymes in prokaryotes, including oxygen atom transfer, sulfur or
proton transfer, hydroxylation, or even nonredox ones. Mo enzymes are widespread
in prokaryotes, and many of them were likely present in LUCA. To date, more than
50-mostly bacterial-Mo enzymes are described in nature. In a few eubacteria and
in many archaea, Mo is replaced by tungsten bound to the same unique
pyranopterin. How Moco is synthesized in bacteria is reviewed as well as the way
until its insertion into apo-Mo-enzymes.
PMID- 26443740
TI - Modulation of Chemical Composition and Other Parameters of the Cell at Different
Exponential Growth Rates.
AB - This review begins by briefly presenting the history of research on the chemical
composition and other parameters of cells of E. coli and S. enterica at different
exponential growth rates. Studies have allowed us to determine the in vivo
strength of promoters and have allowed us to distinguish between factor-dependent
transcriptional control of the promoter and changes in promoter activity due to
changes in the concentration of free functional RNA polymerase associated with
different growth conditions. The total, or bulk, amounts of RNA and protein are
linked to the growth rate, because most bacterial RNA is ribosomal RNA (rRNA).
Since ribosomes are required for protein synthesis, their number and their rate
of function determine the rate of protein synthesis and cytoplasmic mass
accumulation. Many mRNAs made in the presence of amino acids have strong ribosome
binding sites whose presence reduces the expression of all other active genes.
This implies that there can be profound differences in the spectrum of gene
activities in cultures grown in different media that produce the same growth
rate. Five classes of growth-related parameters that are generally useful in
describing or establishing the macromolecular composition of bacterial cultures
are described in detail in this review. A number of equations have been reported
that describe the macromolecular composition of an average cell in an exponential
culture as a function of the culture doubling time and five additional
parameters: the C- and D-periods, protein per origin (PO), ribosome activity, and
peptide chain elongation rate.
PMID- 26443741
TI - Biosynthesis of the Aromatic Amino Acids.
AB - This chapter describes in detail the genes and proteins of Escherichia coli
involved in the biosynthesis and transport of the three aromatic amino acids
tyrosine, phenylalanine, and tryptophan. It provides a historical perspective on
the elaboration of the various reactions of the common pathway converting
erythrose-4-phosphate and phosphoenolpyruvate to chorismate and those of the
three terminal pathways converting chorismate to phenylalanine, tyrosine, and
tryptophan. The regulation of key reactions by feedback inhibition, attenuation,
repression, and activation are also discussed. Two regulatory proteins, TrpR (108
amino acids) and TyrR (513 amino acids), play a major role in transcriptional
regulation. The TrpR protein functions only as a dimer which, in the presence of
tryptophan, represses the expression of trp operon plus four other genes (the
TrpR regulon). The TyrR protein, which can function both as a dimer and as a
hexamer, regulates the expression of nine genes constituting the TyrR regulon.
TyrR can bind each of the three aromatic amino acids and ATP and under their
influence can act as a repressor or activator of gene expression. The various
domains of this protein involved in binding the aromatic amino acids and ATP,
recognizing DNA binding sites, interacting with the alpha subunit of RNA
polymerase, and changing from a monomer to a dimer or a hexamer are all
described. There is also an analysis of the various strategies which allow TyrR
in conjunction with particular amino acids to differentially affect the
expression of individual genes of the TyrR regulon.
PMID- 26443742
TI - Biosynthesis of Cysteine.
AB - The synthesis of L-cysteine from inorganic sulfur is the predominant mechanism by
which reduced sulfur is incorporated into organic compounds. L-cysteineis used
for protein and glutathione synthesis and serves as the primary source of reduced
sulfur in L-methionine, lipoic acid, thiamin, coenzyme A (CoA), molybdopterin,
and other organic molecules. Sulfate and thiosulfate uptake in E. coli and
serovar Typhimurium are achieved through a single periplasmic transport system
that utilizes two different but similar periplasmic binding proteins. Kinetic
studies indicate that selenate and selenite share a single transporter with
sulfate, but molybdate also has a separate transport system. During aerobic
growth, the reduction of sulfite to sulfide is catalyzed by NADPH-sulfite
reductase (SiR), and serovar Typhimurium mutants lacking this enzyme accumulate
sulfite from sulfate, implying that sulfite is a normal intermediate in
assimilatory sulfate reduction. L-Cysteine biosynthesis in serovar Typhimurium
and E. coli ceases almost entirely when cells are grown on L-cysteine or L
cystine, owing to a combination of end product inhibition of serine
transacetylase by L-cysteine and a gene regulatory system known as the cysteine
regulon, wherein genes for sulfate assimilation and alkanesulfonate utilization
are expressed only when sulfur is limiting. In vitro studies with the cysJIH,
cysK, and cysP promoters have confirmed that they are inefficient at forming
transcription initiation complexes without CysB and N-acetyl-L-serine. Activation
of the tauA and ssuE promoters requires Cbl. It has been proposed that the three
serovar Typhimurium anaerobic reductases for sulfite, thiosulfate, and
tetrathionate may function primarily in anaerobic respiration.
PMID- 26443743
TI - Cytochrome c Biogenesis.
AB - Escherichia coli employs several c-type cytochromes, which are found in the
periplasm or on the periplasmic side of the cytoplasmic membrane; they are used
for respiration under different growth conditions. All E. colic-type cytochromes
are multiheme cytochromes; E. coli does not have a monoheme cytochrome c of the
kind found in mitochondria. The attachment of heme to cytochromes c occurs in the
periplasm, and so the apoprotein must be transported across the cytoplasmic
membrane; this step is mediated by the Sec system, which transports unfolded
proteins across the membrane. The protein CcmE has been found to bind heme
covalently via a single bond and then transfer the heme to apocytochromes. It
should be mentioned that far less complex systems for cytochrome c biogenesis
exist in other organisms and that enterobacteria do not function as a
representative model system for the process in general, although plant
mitochondria use the Ccm system found in E. coli. The variety and distribution of
cytochromes and their biogenesis systems reflect their significance and
centrality in cellular bioenergetics, though the necessity for and origin of the
diverse biogenesis systems are enigmatic.
PMID- 26443744
TI - Biosynthesis of Membrane Lipids.
AB - The pathways in Escherichia coli and (largely by analogy) S. enterica remain the
paradigm of bacterial lipid synthetic pathways, although recently considerable
diversity among bacteria in the specific areas of lipid synthesis has been
demonstrated. The structural biology of the fatty acid synthetic proteins is
essentially complete. However, the membrane-bound enzymes of phospholipid
synthesis remain recalcitrant to structural analyses. Recent advances in genetic
technology have allowed the essentialgenes of lipid synthesis to be tested with
rigor, and as expected most genes are essential under standard growth conditions.
Conditionally lethal mutants are available in numerous genes, which facilitates
physiological analyses. The array of genetic constructs facilitates analysis of
the functions of genes from other organisms. Advances in mass spectroscopy have
allowed very accurate and detailed analyses of lipid compositions as well as
detection of the interactions of lipid biosynthetic proteins with one another and
with proteins outside the lipid pathway. The combination of these advances has
resulted in use of E. coli and S. enterica for discovery of new antimicrobials
targeted to lipid synthesis and in deciphering the molecular actions of known
antimicrobials. Finally,roles for bacterial fatty acids other than as membrane
lipid structural components have been uncovered. For example, fatty acid
synthesis plays major roles in the synthesis of the essential enzyme cofactors,
biotin and lipoic acid. Although other roles for bacterial fatty acids, such as
synthesis of acyl-homoserine quorum-sensing molecules, are not native to E. coli
introduction of the relevant gene(s) synthesis of these foreign molecules readily
proceeds and the sophisticated tools available can used to decipher the
mechanisms of synthesis of these molecules.
PMID- 26443745
TI - Promoter Escape by Escherichia coli RNA Polymerase.
AB - Promoter escape is the process that an initiated RNA polymerase (RNAP) molecule
undergoes to achieve the initiation-elongation transition. Having made this
transition, an RNAP molecule would be relinquished from its promoter hold to
perform productive (full-length) transcription. Prior to the transition, this
process is accompanied by abortive RNA formation-the amount and pattern of which
is controlled by the promoter sequence information. Qualitative and quantitative
analysis of abortive/productive transcription from several Escherichia coli
promoters and their sequence variants led to the understanding that a strong
(RNAP-binding) promoter is more likely to be rate limited (during transcription
initiation) at the escape step and produce abortive transcripts. Of the two
subelements in a promoter, the PRR (the core Promoter Recognition Region) was
found to set the initiation frequency and the rate-limiting step, while the ITS
(the Initial Transcribed Sequence region) modulated the ratio of abortive versus
productive transcription. The highly abortive behavior of E. coli RNAP could be
ameliorated by the presence of Gre (transcript cleavage stimulatory) factor(s),
linking the first step in abortive RNA formation by the initial transcribing
complexes (ITC) to RNAP backtracking. The discovery that translocation during the
initiation stage occurs via DNA scrunching provided the source of energy that
converts each ITC into a highly unstable "stressed intermediate." Mapping all of
the biochemical information onto an X-ray crystallographic structural model of an
open complex gave rise to a plausible mechanism of transcription initiation. The
chapter concludes with contemplations of the kinetics and thermodynamics of
abortive initiation-promoter escape.
PMID- 26443746
TI - Generalisability of pharmacoepidemiological studies using restricted prescription
data.
AB - BACKGROUND: Linking medication databases to disease registries enables population
based pharmacoepidemiology research. In Ireland, country-wide dispensing data is
available only from the means-tested government-medical cards scheme. This
restriction may impact generalisability of analyses based on these data. AIM:
Gender was previously identified as predictor of card status so we aimed to
compare women with and without medical cards at the time of ovarian cancer
diagnosis. METHODS: Ovarian cancers diagnosed 2001-2010 were identified from the
National Cancer Registry Ireland. Age, region, deprivation, smoking, employment
and marital status were evaluated using logistic regression for associations with
card status. Cumulative incidence of de novo card receipt post-diagnosis was
assessed. RESULTS: 1778 (52 %) of 3396 women with incident ovarian cancer had a
card at diagnosis (<70:33 %; 70+:87 %). Within those <70, all variables were
significantly associated with card status at diagnosis. 52 % of those without a
card at diagnosis received one post-diagnosis. CONCLUSIONS: Although medical card
coverage within ovarian cancer patients is similar to the general population,
various factors predict card status. Particularly within those under 70, external
validity needs to be considered when interpreting pharamcoepidemiological
analyses using these data.
PMID- 26443747
TI - Characteristics of coronary artery lesion in patients with and without diabetes
mellitus.
AB - PURPOSE: The goal of this study was to compare the coronary atherosclerotic
burden in patients with and without type-2 diabetes by using CT coronary
angiography (CTCA). METHODS: A total of 206 diabetic (mean age 67 +/- 11 years;
male: 136) and 523 non-diabetic patients (mean age 62 +/- 13 years; male: 323)
without history of coronary artery disease (CAD) underwent CTCA. The per-patient
number of diseased coronary segments was determined, and each diseased segment
was classified as showing obstructive lesion (luminal narrowing >50 %) or not.
Coronary angiography was then performed to confirm diagnosis. RESULTS: Diabetics
showed a higher rate of abnormal CAD (76 vs. 53 % of patients; p < 0.0001) and
fewer normal coronary arteries (24 vs. 47 %; p < 0.0001) compared with non
diabetics. Multi-vessel disease was seen more frequently in patients with
diabetes than in patients without diabetes [15 % (n = 22) vs. 7 % (n = 62),
respectively; p = 0.0004]. The per-patient number of segments with plaque (4.5
vs. 2.0, respectively; p < 0.0001) and the number of segments with obstructive
disease (0.9 vs. 0.5, respectively; p = 0.0001) were higher for diabetic patients
than for non-diabetic patients. CONCLUSION: Diabetes was associated with higher
coronary plaque burden.
PMID- 26443748
TI - Stability and accuracy of total and free PSA values in samples stored at room
temperature.
AB - INTRODUCTION: In 2010, an estimated 476,076 total PSA tests were performed in
Ireland, at a cost of ?3.6 million with the majority ordered by general
practitioners. We aimed to replicate storage conditions at room temperature and
see if prolonged storage affected total and free PSA values. METHODS: Blood
samples were taken from 20 male patients in four VACUETTE(r) Serum Separator
tubes (Greiner-Bio-One, Austria) and stored at room temperature (22 degrees C)
for different time intervals (4, 8, 24, 48 h) before being centrifuged and
analyzed. Total PSA (tPSA) and free PSA (fPSA) values were determined using the
Tosoh AIA 1800 assay (Tokyo, Japan). RESULTS: Mean tPSA values were measured at
4, 8, 24 and 48 h with values of 7.9, 8.1, 7.8 and 8.0 MUg/L, respectively.
Values ranged from -1.26 to +2.53 % compared to the initial 4 h interval reading,
indicating tPSA remained consistent at room temperature. The tPSA showed no
significance between groups (ANOVA, p = 0.283). Mean fPSA values at 4, 8, 24 and
48 h were 2.05, 2.04, 1.83, 1.82 MUg/L, respectively. At 24 and 48 h there was
10.73 and 11.22 % reduction, respectively, in fPSA compared to the 4-h time
interval, indicating prolonged storage resulted in reduced fPSA values. After 24
h, there was an 8.8 % reduction in the free/total PSA %. The fPSA showed
significant differences between groups (ANOVA, p = 0.024). CONCLUSIONS: Our
recommendation is that samples that have been stored for prolonged amounts of
time (greater than 24 h) should not be used for free PSA testing.
PMID- 26443749
TI - Outcomes for patients with Guillain-Barre syndrome requiring mechanical
ventilation: a literature review.
AB - BACKGROUND: This is a literature review of outcomes for patients with Guillain
Barre Syndrome (GBS) who require admission to the intensive care unit for
mechanical ventilation. Respiratory distress is the leading cause of death in the
acute phase, and occurs in about 25 % of patients. AIMS: The aim of this review
is to compile, analyse, and summarise the most relevant literature looking at
outcomes for Guillain-Barre (GB) patients requiring admission to the intensive
care unit and mechanical ventilation. METHODS: A PubMed and Google-Scholar
literature search was performed using the key words 'Guillain-Barre, Outcomes,
Mechanical Ventilation, Prognosis, Mortality, ICU. All 7 papers from the years
2000-2014 which assessed outcomes for GBS patients requiring mechanical
ventilation were included, and critically analysed. RESULTS: The parameters
recorded by these studies looked at mortality, disability, length of
hospitalisation, and complications. The mortality of GB patients requiring
mechanical ventilation varied from 8.3 to 20 %, Disability was primarily measured
by the GBS disability scale. One study deemed that a score of 0-1 was a positive
outcome, and found that slightly over half 53.8 % of the patients fulfilled that
criteria. Over half of the mechanically ventilated patients were required to be
admitted for over 3 weeks. Complications during ICU admission are common, with
bed-sores (40 %), pneumonia (30.2 %) and sepsis (17.4) being the most frequently
encountered in one study. CONCLUSION: Accurate data are limited by the fact that
these studies are retrospective, often covering long periods in the past. Larger,
more recent, prospective, multi-centre studies will be required.
PMID- 26443750
TI - Comparison of DNA Methylation and Expression Pattern of S100 and Other Epidermal
Differentiation Complex Genes in Differentiating Keratinocytes.
AB - Epidermal Differentiation Complex (EDC) is a gene cluster on human chromosome 1
q21, which comprises genes encoding four protein families: S100, S100 fused
(SFTP), small proline-rich region (SPRR) and late cornified envelope (LCE)
proteins. Contrary to the latter three families, which group proteins important
for skin barrier formation, the role of S100 proteins has not been well defined
and there are no systematic comparative data concerning their expression in the
epidermis. Furthermore, little is known about epigenetic mechanisms controlling
changes in S100 and other EDC genes expression in differentiating epidermis. In
our study, using real-time PCR, we followed the expression of nine S100 genes at
subsequent stages of differentiation of primary human keratinocytes and found
that they exhibited different expression patterns. Then, we confronted the
expression level in undifferentiated and differentiated keratinocytes with the
extent of DNA methylation within their promoter or intragenic regions assessed by
bisulfite sequencing. Methylation analysis was also performed for three other EDC
genes of known expression pattern (involucrin, loricrin, and NICE-1) and a
recently identified evolutionary conserved region with defined enhancer
properties. The results indicate that altered EDC genes expression is not
accompanied by major changes in DNA methylation.
PMID- 26443751
TI - Factor analysis of the hospital anxiety and depression scale among a Huntington's
disease population.
AB - INTRODUCTION: Depression and anxiety are common in Huntington's disease, a
genetic neurodegenerative disorder. There is a need for measurement tools of mood
to be validated within a Huntington's disease population. The current study aimed
to analyze the factor structure of the Hospital Anxiety and Depression Scale in
Huntington's disease. METHODS: Data from the European Huntington's Disease
Network study REGISTRY 3 were used to undertake a factor analysis of the scale
among a sample of 492 Huntington's disease mutation carriers. The sample was
randomly divided into two equal subsamples and an exploratory factor analysis
conducted on the first subsample suggested a two-factor interpretation, using
eight of the items. A confirmatory factor analysis was then performed to test six
possible models for goodness of fit. RESULTS: A bifactor model, with all items
loading onto a general distress factor, with two group factors, comprising four
depression and four anxiety items, provided the best fit of the data. The
salience of loadings on the bifactor model suggested that loadings were high on
the general factor (accounting for 64% of the variance) and low on the group
factors (21% for anxiety and 15% for depression). CONCLUSIONS: The findings
suggest that eight items from the scale perform well among the sample. Consistent
with recent developments in modeling the Hospital Anxiety and Depression Scale, a
bifactor interpretation for an eight-item version outperformed other extant
models. Our findings provide support for an eight-item version of the scale to be
used as a measure of general distress within Huntington's disease populations.
PMID- 26443753
TI - Glycogen: Biosynthesis and Regulation.
AB - The accumulation of glycogen occurs in Escherichia coli and Salmonella enterica
serovar Typhimurium as well as in many other bacteria. Glycogen will be formed
when there is an excess of carbon under conditions in which growth is limited due
to the lack of a growth nutrient, e.g., a nitrogen source. The structural genes
of the glycogen biosynthetic enzymes of E. coli and S. serovar Typhimurium have
been cloned previously, and that has provided insights in the genetic regulation
of glycogen synthesis. An important aspect of the regulation of glycogen
synthesis is the allosteric regulation of the ADP-Glc PPase. The current
information, views, and concepts regarding the regulation of enzyme activity and
the expression of the glycogen biosynthetic enzymes are presented in this review.
The recent information on the amino acid residues critical for the activity of
both glycogen synthase and branching enzyme (BE) is also presented. The residue
involved in catalysis in the E. coli ADP-Glc PPase was determined by comparing a
predicted structure of the enzyme with the known three-dimensional structures of
sugar-nucleotide PPase domains. The molecular cloning of the E. coliglg K-12
structural genes greatly facilitated the subsequent study of the genetic
regulation of bacterial glycogen biosynthesis. Results from studies of glycogen
excess E. coli B mutants SG3 and AC70R1, which exhibit enhanced levels of the
enzymes in the glycogen synthesis pathway (i.e., they are derepressed mutants),
suggested that glycogen synthesis is under negative genetic regulation.
PMID- 26443754
TI - Oxygen as Acceptor.
AB - Like most bacteria, Escherichia coli has a flexible and branched respiratory
chain that enables the prokaryote to live under a variety of environmental
conditions, from highly aerobic to completely anaerobic. In general, the
bacterial respiratory chain is composed of dehydrogenases, a quinone pool, and
reductases. Substrate specific dehydrogenases transfer reducing equivalents from
various donor substrates (NADH, succinate, glycerophoshate, formate, hydrogen,
pyruvate, and lactate) to a quinone pool (menaquinone, ubiquinone, and
demethylmenoquinone). Then electrons from reduced quinones (quinols) are
transferred by terminal reductases to different electron acceptors. Under aerobic
growth conditions, the terminal electron acceptor is molecular oxygen. A transfer
of electrons from quinol to O2 is served by two major oxidoreductases (oxidases),
cytochrome bo3 and cytochrome bd. Terminal oxidases of aerobic respiratory chains
of bacteria, which use O2 as the final electron acceptor, can oxidize one of two
alternative electron donors, either cytochrome c or quinol. This review compares
the effects of different inhibitors on the respiratory activities of cytochrome
bo3 and cytochrome bd in E. coli. It also presents a discussion on the genetics
and the prosthetic groups of cytochrome bo3 and cytochrome bd. The E. coli
membrane contains three types of quinones which all have an octaprenyl side chain
(C40). It has been proposed that the bo3 oxidase can have two ubiquinone-binding
sites with different affinities. The spectral properties of cytochrome bd-II
closely resemble those of cydAB-encoded cytochrome bd.
PMID- 26443756
TI - Structure and Assembly of Escherichia coli Capsules.
AB - The capsule is a cell surface structure composed of long-chain polysaccharides
that envelops many isolates of Escherichia coli. It protects the cell against
host defenses or physical environmental stresses, such as desiccation. The
component capsular polysaccharides (CPSs) are major surface antigens in E. coli.
They are named K antigens (after the German word Kapsel). Due to variations in
CPS structures, more than 80 serologically unique K antigens exist in E. coli.
Despite the hypervariability in CPS structures, only two capsule-assembly
strategies exist in E. coli. These have led to the assignment of group 1 and
group 2 capsules, and many of the key elements of the corresponding assembly
pathways have been resolved. Structural features, as well as genetic and
regulatory variations, give rise to additional groups 3 and 4. These employ the
same biosynthesis processes described in groups 2 and 1, respectively. Each
isolate possesses a distinctive set of cytosolic and inner-membrane enzymes,
which generate a precise CPS structure, defining a given K serotype. Once
synthesized, a multiprotein complex is needed to translocate the nascent CPS
across the Gram-negative cell envelope to the outer surface of the outer
membrane, where the capsule structure is assembled. While the translocation
machineries for group 1 and group 2 CPSs are fundamentally different from one
another, they possess no specificity for a given CPS structure. Each is conserved
in all isolates producing capsules belonging to a particular group.
PMID- 26443752
TI - Late initiation of combination antiretroviral therapy in Canada: a call for a
national public health strategy to improve engagement in HIV care.
AB - INTRODUCTION: Combination antiretroviral therapy (ART) significantly decreases
morbidity, mortality and HIV transmission. We aimed to characterize the timing of
ART initiation based on CD4 cell count from 2000 to 2012 and identify factors
associated with late initiation of treatment. METHODS: Participants from the
Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults
initiating ART naively after 1 January 2000, in three Canadian provinces (British
Columbia, Ontario and Quebec) were included. Late initiation was defined as a CD4
count <200 cells/mm(3) or an AIDS-defining illness before ART initiation
(baseline). Temporal trends were assessed using the Cochran-Armitage test, and
independent correlates of late initiation were identified using logistic
regression. RESULTS: In total, 8942 participants (18% female) of median age 40
years (Q1-Q3 33-47) were included. The median baseline CD4 count increased from
190 cells/mm(3) (Q1-Q3 80-320) in 2000 to 360 cells/mm(3) (Q1-Q3 220-490) in 2012
(p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200
cells/mm(3) or AIDS-defining illness. Late initiation was more common among
women, non-MSM, older individuals, participants from Ontario and BC (vs. Quebec),
persons with injection drug use (IDU) history and individuals starting ART in
earlier calendar years. In sub-analysis exploring recent (2008 to 2012)
predictors using an updated CD4 criterion (<350 cells/mm(3)), IDU and residence
in BC (vs. Quebec) were no longer significant correlates of late initiation.
CONCLUSIONS: This analysis documents increasing baseline CD4 counts over time
among Canadians initiating ART. However, CD4 counts at ART initiation remain
below contemporary treatment guidelines, highlighting the need for strategies to
improve earlier engagement in HIV care.
PMID- 26443755
TI - Biosynthesis of Thiamin Pyrophosphate.
AB - The biosynthesis of thiamin pyrophosphate (TPP) in prokaryotes, as represented by
the Escherichia coli and the Bacillus subtilis pathways, is summarized in this
review. The thiazole heterocycle is formed by the convergence of three separate
pathways. First, the condensation of glyceraldehyde 3-phosphate and pyruvate,
catalyzed by 1-deoxy-D-xylulose 5-phosphate synthase (Dxs), gives 1-deoxy-D
xylulose 5-phosphate (DXP). Next, the sulfur carrier protein ThiS-COO- is
converted to its carboxyterminal thiocarboxylate in reactions catalyzed by ThiF,
ThiI, and NifS (ThiF and IscS in B. subtilis). Finally, tyrosine (glycine in B.
subtilis) is converted to dehydroglycine by ThiH (ThiO in B. subtilis). Thiazole
synthase (ThiG) catalyzes the complex condensation of ThiS-COSH, dehydroglycine,
and DXP to give a thiazole tautomer, which is then aromatized to carboxythiazole
phosphate by TenI (B. subtilis). Hydroxymethyl pyrimidine phosphate (HMP-P) is
formed by a complicated rearrangement reaction of 5-aminoimidazole ribotide (AIR)
catalyzed by ThiC. ThiD then generates hydroxymethyl pyrimidine pyrophosphate.
The coupling of the two heterocycles and decarboxylation, catalyzed by thiamin
phosphate synthase (ThiE), gives thiamin phosphate. A final phosphorylation,
catalyzed by ThiL, completes the biosynthesis of TPP, the biologically active
form of the cofactor. This review reviews the current status of mechanistic and
structural studies on the enzymes involved in this pathway. The availability of
multiple orthologs of the thiamin biosynthetic enzymes has also greatly
facilitated structural studies, and most of the thiamin biosynthetic and salvage
enzymes have now been structurally characterized.
PMID- 26443757
TI - NLRs: Nucleotide-Binding Domain and Leucine-Rich-Repeat-Containing Proteins.
AB - Eukaryotes have evolved strategies to detect microbial intrusion and instruct
immune responses to limit damage from infection. Recognition of microbes and
cellular damage relies on the detection of microbe-associated molecular patterns
(MAMPs, also called PAMPS, or pathogen-associated molecular patterns) and so
called "danger signals" by various families of host pattern recognition receptors
(PRRs). Members of the recently identified protein family of nucleotide-binding
domain andleucine-rich-repeat-containing proteins (NLR), including Nod1, Nod2,
NLRP3, and NLRC4, have been shown to detect specific microbial motifs and danger
signals for regulating host inflammatory responses. Moreover, with the discovery
that polymorphisms in NOD1, NOD2, NLRP1, and NLRP3 are associated with
susceptibility to chronic inflammatory disorders, the view has emerged that NLRs
act not only as sensors butalso can serve as signaling platforms for instructing
and balancing host immune responses. In this chapter, we explore the functions of
these intracellular innate immune receptors and examine their implication in
inflammatory diseases.
PMID- 26443759
TI - Envelope Stress Responses.
AB - The gram-negative bacterial envelope is a complex extracytoplasmic compartment
responsible for numerous cellular processes. Among its most important functions
is its service as the protective layer separating the cytoplasmic space from the
ever-changing external environment. To adapt to the diverse conditions
encountered both in the environment and within the mammalian host, Escherichia
coli and Salmonella species have evolved six independent envelope stress response
systems . This review reviews the sE response, the CpxAR and BaeSR two-component
systems (TCS) , the phage shock protein response, and the Rcs phosphorelay
system. These five signal transduction pathways represent the most studied of the
six known stress responses. The signal for adhesion to abiotic surfaces enters
the pathway through the novel outer membrane lipoprotein NlpE, and activation on
entry into the exponential phase of growth occurs independently of CpxA .
Adhesion could disrupt NlpE causing unfolding of its unstable N-terminal domain,
leading to activation of the Cpx response. The most recent class of genes added
to the Cpx regulon includes those involved in copper homeostasis. Two separate
microarray experiments revealed that exposure of E. coli cells to high levels of
external copper leads to upregulation of several Cpx regulon members. The BaeSR
TCS has also been shown to mediate drug resistance in Salmonella. Similar to E.
coli, the Bae pathway of Salmonella enterica mediates resistance to oxacillin,
novobiocin, deoxycholate, beta-lactams, and indole.
PMID- 26443760
TI - The Nucleoid: an Overview.
AB - This review provides a brief review of the current understanding of the structure
function relationship of the Escherichia coli nucleoid developed after the
overview by Pettijohn focusing on the physical properties of nucleoids. Isolation
of nucleoids requires suppression of DNA expansion by various procedures. The
ability to control the expansion of nucleoids in vitro has led to purification of
nucleoids for chemical and physical analyses and for high-resolution imaging.
Isolated E. coli genomes display a number of individually intertwined supercoiled
loops emanating from a central core. Metabolic processes of the DNA double helix
lead to three types of topological constraints that all cells must resolve to
survive: linking number, catenates, and knots. The major species of nucleoid core
protein share functional properties with eukaryotic histones forming chromatin;
even the structures are different from histones. Eukaryotic histones play dynamic
roles in the remodeling of eukaryotic chromatin, thereby controlling the access
of RNA polymerase and transcription factors to promoters. The E. coli genome is
tightly packed into the nucleoid, but, at each cell division, the genome must be
faithfully replicated, divided, and segregated. Nucleoid activities such as
transcription, replication, recombination, and repair are all affected by the
structural properties and the special conformations of nucleoid. While it is
apparent that much has been learned about the nucleoid, it is also evident that
the fundamental interactions organizing the structure of DNA in the nucleoid
still need to be clearly defined.
PMID- 26443761
TI - DNA Topoisomerases.
AB - DNA topoisomerases are enzymes that control the topological state of DNA in all
cells; they have central roles in DNA replication and transcription. They are
classified into two types, I and II, depending on whether they catalyze reactions
involving the breakage of one or both strands of DNA. Structural and mechanistic
distinctions have led to further classifications: IA, IB, IC, IIA, and IIB. The
essence of the topoisomerase reaction is the ability of the enzymes to stabilize
transient breaks in DNA, via the formation of tyrosyl-phosphate covalent
intermediates. The essential nature of topoisomerases and their ability to
stabilize DNA breaks has led to them being key targets for antibacterial and
anticancer agents. This chapter reviews the basic features of topoisomerases
focussing mainly on the prokaryotic enzymes. We highlight recent structural
advances that have given new insight into topoisomerase mechanisms and into the
molecular basis of the action of topoisomerase-specific drugs.
PMID- 26443762
TI - Cell-to-Cell Signaling in Escherichia coli and Salmonella.
AB - Bacteria must be able to respond rapidly to changes in the environment in order
to survive. One means of coordinating gene expression relies on tightly regulated
and complex signaling systems. One of the first signaling systems that was
described in detail is quorum sensing (QS). During QS, a bacterial cell produces
and secretes a signaling molecule called an autoinducer (AI). As the density of
the bacterial population increases, so does the concentration of secreted AI
molecules, thereby allowing a bacterial species to coordinate gene expression
based on population density. Subsequent studies have demonstrated that bacteria
are also able to detect signal molecules produced by other species of bacteria as
well as hormones produced by their mammalian hosts. These types of signaling
interactions have been termed cell-to-cell signaling because the interaction does
not rely on a threshold concentration of bacterial cells. This review discusses
the three main types of cell-to-cell signaling mechanisms used by E. coli and
Salmonella, including the LuxR process, in which E. coli and Salmonella detect
signals produced by other species of bacteria; the LuxS/AI-2 system, in which E.
coli and Salmonella participate in intra- and interspecies signaling; and the AI
3/ epinephrine/norepinephrine system, in which E. coli and Salmonella recognize
self-produced AI, signal produced by other microbes, and/or the human stress
hormones epinephrine or norepinephrine.
PMID- 26443758
TI - Biogenesis and Homeostasis of Nicotinamide Adenine Dinucleotide Cofactor.
AB - Universal and ubiquitous redox cofactors, nicotinamide adenine dinucleotide (NAD)
and its phosphorylated analog (NADP), collectively contribute to approximately
12% of all biochemical reactions included in the metabolic model of Escherichia
coli K-12. A homeostasis of the NAD pool faithfully maintained by the cells
results from a dynamic balance in a network of NAD biosynthesis, utilization,
decomposition, and recycling pathways that is subject to tight regulation at
various levels. A brief overview of NAD utilization processes is provided in this
review, including some examples of nonredox utilization. The review focuses
mostly on those aspects of NAD biogenesis and utilization in E. coli and
Salmonella that emerged within the past 12 years. The first pyridine nucleotide
cycle (PNC) originally identified in mammalian systems and termed the Preiss
Handler pathway includes a single-step conversion of niacin (Na) to NaMN by
nicotinic acid phosphoribosyltransferase (PncB). In E. coli and many other
prokaryotes, this enzyme, together with nicotinamide deamidase (PncA), compose
the major pathway for utilization of the pyridine ring in the form of amidated
(Nm) or deamidated (Na) precursors. The existence of various regulatory
mechanisms and checkpoints that control the NAD biosynthetic machinery reflects
the importance of maintaining NAD homeostasis in a variety of growth conditions.
Among the most important regulatory mechanisms at the level of individual enzymes
are a classic feedback inhibition of NadB, the first enzyme of NAD de novo
biosynthesis, by NAD and a metabolic regulation of NadK by reduced cofactors.
PMID- 26443763
TI - Uropathogenic Escherichia coli.
AB - The urinary tract is among the most common sites of bacterial infection, and
Escherichia coli is by far the most common species infecting this site.
Individuals at high risk for symptomatic urinary tract infection (UTI) include
neonates, preschool girls, sexually active women, and elderly women and men. E.
coli that cause the majority of UTIs are thought to represent only a subset of
the strains that colonize the colon. E. coli strains that cause UTIs are termed
uropathogenic E. coli (UPEC). In general, UPEC strains differ from commensal E.
coli strains in that the former possess extragenetic material, often on
pathogenicity-associated islands (PAIs), which code for gene products that may
contribute to bacterial pathogenesis. Some of these genes allow UPEC to express
determinants that are proposed to play roles in disease. These factors include
hemolysins, secreted proteins, specific lipopolysaccharide and capsule types,
iron acquisition systems, and fimbrial adhesions. The current dogma of bacterial
pathogenesis identifies adherence, colonization, avoidance of host defenses, and
damage to host tissues as events vital for achieving bacterial virulence. These
considerations, along with analysis of the E. coli CFT073, UTI89, and 536 genomes
and efforts to identify novel virulence genes should advance the field
significantly and allow for the development of a comprehensive model of
pathogenesis for uropathogenic E. coli.Further study of the adaptive immune
response to UTI will be especially critical to refine our understanding and
treatment of recurrent infections and to develop vaccines.
PMID- 26443764
TI - Osmotic Stress.
AB - Escherichia coli and Salmonella encounter osmotic pressure variations in natural
environments that include host tissues, food, soil, and water. Osmotic stress
causes water to flow into or out of cells, changing their structure, physics, and
chemistry in ways that perturb cell functions. E. coli and Salmonella limit
osmotically induced water fluxes by accumulating and releasing electrolytes and
small organic solutes, some denoted compatible solutes because they accumulate to
high levels without disturbing cell functions. Osmotic upshifts inhibit membrane
based energy transduction and macromolecule synthesis while activating existing
osmoregulatory systems and specifically inducing osmoregulatory genes. The
osmoregulatory response depends on the availability of osmoprotectants (exogenous
organic compounds that can be taken up to become compatible solutes). Without
osmoprotectants, K+ accumulates with counterion glutamate, and compatible solute
trehalose is synthesized. Available osmoprotectants are taken up via transporters
ProP, ProU, BetT, and BetU. The resulting compatible solute accumulation
attenuates the K+ glutamate response and more effectively restores cell hydration
and growth. Osmotic downshifts abruptly increase turgor pressure and strain the
cytoplasmic membrane. Mechanosensitive channels like MscS and MscL open to allow
nonspecific solute efflux and forestall cell lysis. Research frontiers include
(i) the osmoadaptive remodeling of cell structure, (ii) the mechanisms by which
osmotic stress alters gene expression, (iii) the mechanisms by which transporters
and channels detect and respond to osmotic pressure changes, (iv) the
coordination of osmoregulatory programs and selection of available
osmoprotectants, and (v) the roles played by osmoregulatory mechanisms as E. coli
and Salmonella survive or thrive in their natural environments.
PMID- 26443766
TI - Structural Basis for the Decoding Mechanism.
AB - The bacterial ribosome is a complex macromolecular machine that deciphers the
genetic code with remarkable fidelity. During the elongation phase of protein
synthesis, the ribosome selects aminoacyl-tRNAs as dictated by the canonical base
pairing between the anticodon of the tRNA and the codon of the messenger RNA. The
ribosome's participation in tRNA selection is active rather than passive, using
conformational changes of conserved bases of 16S rRNA to directly monitor the
geometry of codon-anticodon base pairing. The tRNA selection process is divided
into an initial selection step and a subsequent proofreading step, with the
utilization of two sequential steps increasing the discriminating power of the
ribosome far beyond that which could be achieved based on the thermodynamics of
codon-anticodon base pairing stability. The accuracy of decoding is impaired by a
number of antibiotics and can be either increased or decreased by various
mutations in either subunit of the ribosome, in elongation factor Tu, and in
tRNA. In this chapter we will review our current understanding of various forces
that determine the accuracy of decoding by the bacterial ribosome.
PMID- 26443765
TI - Biosynthesis of Menaquinone (Vitamin K2) and Ubiquinone (Coenzyme Q).
AB - Escherichia coli and Salmonella contain the naphthoquinones menaquinone (MK;
vitamin K2) and demethylmenaquinone and the benzoquinone ubiquinone (coenzyme Q;
Q). Both quinones are derived from the shikimate pathway, which has been called a
"metabolic tree with many branches." There are two different pathways for the
biosynthesis of the naphthoquinones. The vast majority of prokaryotes, including
E. coli and Salmonella, and the plants use the o-succinylbenzoate pathway, while
a minority uses the futalosine pathway. The quinone nucleus of Q is derived
directly from chorismate, while that of MK is derived from chorismate via
isochorismate. The prenyl side chains of both quinones are from isopentenyl
diphosphate formed by the 2-C-methyl-D-erythritol 4-phosphate (non-mevalonate)
pathway and the methyl groups are from S-adenosylmethionine. In addition, MK
biosynthesis requires 2-ketoglutarate and cofactors ATP, coenzyme A, and thiamine
pyrophosphate. Despite the fact that both quinones originate from the shikimate
pathway, there are important differences in their biosyntheses. The prenyl side
chain in MK biosynthesis is introduced at the penultimate step, accompanied by
decarboxylation, whereas in Q biosynthesis it is introduced at the second step,
with retention of the carboxyl group. In MK biosynthesis, all the reactions of
the pathway up to prenylation are carried out by soluble enzymes, whereas all the
enzymes involved in Q biosynthesis except the first are membrane bound. In MK
biosynthesis, the last step is a C-methylation; in Q biosynthesis, the last step
is an O-methylation. In Q biosynthesis a second C-methylation and O-methylation
take place in the middle part of the pathway. Despite the fact that Q and MK
biosyntheses diverge at chorismate, the C-methylations in both pathways are
carried out by the same methyltransferase.
PMID- 26443769
TI - DNA Methylation.
AB - The DNA of Escherichia coli contains 19,120 6-methyladenines and 12,045 5
methylcytosines in addition to the four regular bases, and these are formed by
the postreplicative action of three DNA methyltransferases. The majority of the
methylated bases are formed by the Dam and Dcmmethyltransferases encoded by the
dam (DNA adenine methyltransferase) and dcm (DNA cytosine methyltransferase)
genes. Although not essential, Dam methylation is important for strand
discrimination during repair of replication errors, controlling the frequency of
initiation of chromosome replication at oriC, and regulation of transcription
initiation at promoters containing GATC sequences. In contrast, there is no known
function for Dcm methylation, although Dcm recognition sites constitute sequence
motifs for Very Short Patch repair of T/G base mismatches. In certain bacteria
(e.g., Vibrio cholera and Caulobactercrescentus) adenine methylation is
essential, and in C.crescentus it is important for temporal gene expression
which, in turn, is required for coordination of chromosome initiation,
replication, and division. In practical terms, Dam and Dcm methylation can
inhibit restriction enzyme cleavage,decrease transformation frequency in certain
bacteria,and decrease the stability of short direct repeats andare necessary for
site-directed mutagenesis and to probe eukaryotic structure and function.
PMID- 26443770
TI - Adaptive Immune Responses during Salmonella Infection.
AB - The interaction betweenSalmonella and its host is complex and dynamic: the host
mounts an immune defense against the pathogen, which in turn acts to reduce,
evade, or exploit these responses to successfully colonize the host. Although the
exact mechanisms mediating protective immunity are poorly understood, it is known
that T cells are a critical component of immunity to Salmonella infection, and a
robust T-cell response is required for both clearance of primary infection and
resistance to subsequent challenge. B-cell functions, including but not limited
to antibody production, are also required for generation of protective immunity.
Additionally, interactions among host cells are essential. For example, antigen
presenting cells (including B cells) express cytokines that participate in CD4+ T
cell activation and differentiation. Differentiated CD4+ T cells secrete
cytokines that have both autocrine and paracrine functions, including recruitment
and activation of phagocytes, and stimulation of B cell isotype class switching
and affinity maturation. Multiple bacterium-directed mechanisms, including
altered antigen expression and bioavailability and interference with antigen
presenting cell activation and function, combine to modify Salmonella's
"pathogenic signature" in order to minimize its susceptibility to host immune
surveillance. Therefore, a more complete understanding of adaptive immune
responses may provide insights into pathogenic bacterial functions. Continued
identification of adaptive immune targets will guide rational vaccine
development, provide insights into host functions required to resist Salmonella
infection, and correspondingly provide valuable reagents for defining the
critical pathogenic capabilities of Salmonella that contribute to their success
in causing acute and chronic infections.
PMID- 26443767
TI - Replisome Dynamics during Chromosome Duplication.
AB - This review describes the components of the Escherichia coli replisome and the
dynamic process in which they function and interact under normal conditions. It
also briefly describes the behavior of the replisome during situations in which
normal replication fork movement is disturbed, such as when the replication fork
collides with sites of DNA damage. E. coli DNA Pol III was isolated first from a
polA mutant E. coli strain that lacked the relatively abundant DNA Pol I
activity. Further biochemical studies, and the use of double mutant strains,
revealed Pol III to be the replicative DNA polymerase essential to cell
viability. In a replisome, DnaG primase must interact with DnaB for activity, and
this constraint ensures that new RNA primers localize to the replication fork.
The leading strand polymerase continually synthesizes DNA in the direction of the
replication fork, whereas the lagging-strand polymerase synthesizes short,
discontinuous Okazaki fragments in the opposite direction. Discontinuous lagging
strand synthesis requires that the polymerase rapidly dissociate from each new
completed Okazaki fragment in order to begin the extension of a new RNA primer.
Lesion bypass can be thought of as a two-step reaction that starts with the
incorporation of a nucleotide opposite the lesion, followed by the extension of
the resulting distorted primer terminus. A remarkable property of E. coli, and
many other eubacterial organisms, is the speed at which it propagates. Rapid cell
division requires the presence of an extremely efficient replication machinery
for the rapid and faithful duplication of the genome.
PMID- 26443771
TI - Oxidative Stress.
AB - The ancestors of Escherichia coli and Salmonella ultimately evolved to thrive in
air-saturated liquids, in which oxygen levels reach 210 MUM at 37 degrees C.
However, in 1976 Brown and colleagues reported that some sensitivity persists:
growth defects still become apparent when hyperoxia is imposed on cultures of E.
coli. This residual vulnerability was important in that it raised the prospect
that normal levels of oxygen might also injure bacteria, albeit at reduced rates
that are not overtly toxic. The intent of this article is both to describe the
threat that molecular oxygen poses for bacteria and to detail what we currently
understand about the strategies by which E. coli and Salmonella defend themselves
against it. E. coli mutants that lack either superoxide dismutases or catalases
and peroxidases exhibit a variety of growth defects. These phenotypes constitute
the best evidence that aerobic cells continually generate intracellular
superoxide and hydrogen peroxide at potentially lethal doses. Superoxide has
reduction potentials that allow it to serve in vitro as either a weak univalent
reductant or a stronger univalent oxidant. The addition of micromolar hydrogen
peroxide to lab media will immediately block the growth of most cells, and
protracted exposure will result in the loss of viability. The need for inducible
antioxidant systems seems especially obvious for enteric bacteria, which move
quickly from the anaerobic gut to fully aerobic surface waters or even to ROS
perfused phagolysosomes. E. coli and Salmonella have provided two paradigmatic
models of oxidative-stress responses: the SoxRS and OxyR systems.
PMID- 26443772
TI - Transition Metal Homeostasis.
AB - This chapter focuses on transition metals. All transition metal cations are toxic
those that are essential for Escherichia coli and belong to the first transition
period of the periodic system of the element and also the "toxic-only" metals
with higher atomic numbers. Common themes are visible in the metabolism of these
ions. First, there is transport. High-rate but low-affinity uptake systems
provide a variety of cations and anions to the cells. Control of the respective
systems seems to be mainly through regulation of transport activity (flux
control), with control of gene expression playing only a minor role. If these
systems do not provide sufficient amounts of a needed ion to the cell, genes for
ATP-hydrolyzing high-affinity but low-rate uptake systems are induced, e.g., ABC
transport systems or P-type ATPases. On the other hand, if the amount of an ion
is in surplus, genes for efflux systems are induced. By combining different kinds
of uptake and efflux systems with regulation at the levels of gene expression and
transport activity, the concentration of a single ion in the cytoplasm and the
composition of the cellular ion "bouquet" can be rapidly adjusted and carefully
controlled. The toxicity threshold of an ion is defined by its ability to produce
radicals (copper, iron, chromate), to bind to sulfide and thiol groups (copper,
zinc, all cations of the second and third transition period), or to interfere
with the metabolism of other ions. Iron poses an exceptional metabolic problem
due its metabolic importance and the low solubility of Fe(III) compounds,
combined with the ability to cause dangerous Fenton reactions. This dilemma for
the cells led to the evolution of sophisticated multi-channel iron uptake and
storage pathways to prevent the occurrence of unbound iron in the cytoplasm.
Toxic metals like Cd2+ bind to thiols and sulfide, preventing assembly of iron
complexes and releasing the metal from iron-sulfur clusters. In the unique case
of mercury, the cation can be reduced to the volatile metallic form. Interference
of nickel and cobalt with iron is prevented by the low abundance of these metals
in the cytoplasm and their sequestration by metal chaperones, in the case of
nickel, or by B12 and its derivatives, in the case of cobalt. The most dangerous
metal, copper, catalyzes Fenton-like reactions, binds to thiol groups, and
interferes with iron metabolism. E. coli solves this problem probably by
preventing copper uptake, combined with rapid efflux if the metal happens to
enter the cytoplasm.
PMID- 26443773
TI - Not the last word: arthrostasis.
PMID- 26443768
TI - Biosynthesis of Histidine.
AB - The biosynthesis of histidine in Escherichia coli and Salmonella typhimurium has
been an important model system for the study of relationships between the flow of
intermediates through a biosynthetic pathway and the control of the genes
encoding the enzymes that catalyze the steps in a pathway. This article provides
a comprehensive review of the histidine biosynthetic pathway and enzymes,
including regulation of the flow of intermediates through the pathway and
mechanisms that regulate the amounts of the histidine biosynthetic enzymes. In
addition, this article reviews the structure and regulation of the histidine
(his) biosynthetic operon, including transcript processing, Rho-factor-dependent
"classical" polarity, and the current model of his operon attenuation control.
Emphasis is placed on areas of recent progress. Notably, most of the enzymes that
catalyze histidine biosynthesis have recently been crystallized, and their
structures have been determined. Many of the histidine biosynthetic intermediates
are unstable, and the histidine biosynthetic enzymes catalyze some chemically
unusual reactions. Therefore, these studies have led to considerable mechanistic
insight into the pathway itself and have provided deep biochemical understanding
of several fundamental processes, such as feedback control, allosteric
interactions, and metabolite channeling. Considerable recent progress has also
been made on aspects of his operon regulation, including the mechanism of
pp(p)Gpp stimulation of his operon transcription, the molecular basis for
transcriptional pausing by RNA polymerase, and pathway evolution. The progress in
these areas will continue as sophisticated new genomic, metabolomic, proteomic,
and structural approaches converge in studies of the histidine biosynthetic
pathway and mechanisms of control of his biosynthetic genes in other bacterial
species.
PMID- 26443774
TI - Is there an association between whole-body pain with osteoarthritis-related knee
pain, pain catastrophizing, and mental health?
AB - BACKGROUND: Greater levels of self-reported pain, pain catastrophizing, and
depression have been shown to be associated with persistent pain and functional
limitation after surgeries such as TKA. It would be useful for clinicians to be
able to measure these factors efficiently. QUESTIONS/PURPOSES: We asked: (1) What
is the association of whole-body pain with osteoarthritis (OA)-related knee pain,
function, pain catastrophizing, and mental health? (2) What is the sensitivity
and specificity for different cutoffs for body pain diagram region categories in
relation to pain catastrophizing? METHODS: Patients (n = 267) with knee OA
undergoing elective TKA at one academic center and two community orthopaedic
centers were enrolled before surgery in a prospective cohort study.
Questionnaires included the WOMAC Pain and Function Scales, Pain Catastrophizing
Scale (PCS), Mental Health Inventory-5 (MHI-5), and a pain body diagram. The
diagram documents pain in 19 anatomic areas. Based on the distribution of the
anatomic areas, we established six different body regions. Our analyses excluded
the index (surgically treated) knee. Linear regression was used to evaluate the
association between the total number of nonindex painful sites on the whole-body
pain diagram and measures of OA-related pain and function, mental health, and
pain catastrophizing. Generalized linear regression was used to evaluate the
association between the number of painful nonindex body regions (categorized as
0; 1-2; or 3-6) with our measures of interest. All models were adjusted for age,
sex, and number of comorbid conditions. The cohort included 63% females and the
mean age was 66 years (SD, 9 years). With removal of the index knee, the median
pain diagram score was 2 (25(th), 75(th) percentiles, 1, 4) with a range of 0 to
15. The median number of painful body regions was 2 (25(th), 75(th) percentiles,
1, 3). RESULTS: After adjusting for age, sex, and number of comorbid conditions,
we found modest associations between painful body region categories and mean
scores for WOMAC physical function (r = 0.22, p < 0.001), WOMAC pain (r = 0.20, p
= 0.001), MHI-5 (r = -0.31, p < 0.001), and PCS (r = 0.27, p < 0.001). A nonindex
body pain region score greater than 0 had 100% (95% CI, 75%-100%) sensitivity for
a pain catastrophizing score greater than 30 but a specificity of just 23% (95%
CI, 18%-29%) . A score of 3 or greater had greater specificity (73%; 95% CI, 66%
79%) but lower sensitivity (53%; 95% CI, 27%-78%). CONCLUSIONS: We found modest
associations between the number of painful sites on a whole-body pain diagram and
the number of painful body regions and measures of OA-related pain, function,
pain catastrophizing, and mental health. Patients with higher self-reported body
pain region scores might benefit from further evaluation for depression and pain
catastrophizing. LEVEL OF EVIDENCE: Level III, therapeutic study.
PMID- 26443776
TI - Efficacy of Plectranthus glandulosus (Lamiaceae) and Callistemon rigidus
(Myrtaceae) Leaf Extract Fractions to Callosobruchus maculatus (Coleoptera:
Bruchidae).
AB - As part of on-going efforts to use eco-friendly alternatives to chemical
pesticides, methanol crude extracts of Plectranthus glandulosus and Callistemon
rigidus leaves were sequentially fractionated in hexane, chloroform, ethyl
acetate, and methanol to establish the most active fraction(s) against
Callosobruchus maculatus in cowpea. Cowpea seeds (25 g) were treated with 0.5, 1,
2, and 4 g/kg of extract to evaluate the contact toxicity and F1 progeny
production of the beetles in the laboratory. Mortality was recorded 1, 3, and 7 d
postexposure. P. glandulosus hexane fraction was more toxic than the other
fractions recording 100% mortality at 4 g/kg, within 7 d with LC50 of 0.39 g/kg.
Hexane fraction of C. rigidus showed superior toxicity, causing 100% mortality at
4 g/kg within only 1 d of exposure with LC50 of 1.02 g/kg. All the fractions
greatly reduced progeny emergence, with C. rigidus hexane fraction being the best
progeny inhibitor. Fractions of P. glandulosus and C. rigidus leaves had
sufficient efficacy to be a component of storage pest management package for C.
maculatus.
PMID- 26443775
TI - Patients With Thumb Carpometacarpal Arthritis Have Quantifiable Characteristic
Expectations That Can Be Measured With a Survey.
AB - BACKGROUND: Although patient expectations associated with major orthopaedic
conditions have shown clinically relevant and variable effects on outcomes,
expectations associated with thumb carpometacarpal (CMC) arthritis have not been
identified, described, or analyzed before, to our knowledge. QUESTIONS/PURPOSES:
We asked: (1) Do patients with thumb CMC arthritis express characteristic
expectations that are quantifiable and have measurable frequency? (2) Can a
survey on expectations developed from patient-derived data quantitate
expectations in patients with thumb CMC arthritis? METHODS: The study was a
prospective cohort study. The first phase was a 12-month-period involving
interviews of 42 patients with thumb CMC arthritis to define their expectations
of treatment. The interview process used techniques and principles of qualitative
methodology including open-ended interview questions, unrestricted time, and
study size determined by data saturation. Verbatim responses provided content for
the draft survey. The second phase was a 12-month period assessing the survey for
test-retest reliability with the recruitment of 36 participants who completed the
survey twice. The survey was finalized from clinically relevant content,
frequency of endorsement, weighted kappa values for concordance of responses, and
intraclass coefficient and Cronbach's alpha for interrater reliability and
internal consistency. RESULTS: Thirty-two patients volunteered 256 characteristic
expectations, which consisted of 21 discrete categories. Expectations with
similar concepts were combined by eliminating redundancy while maintaining
original terminology. These were reduced to 19 items that comprised a one-page
survey. This survey showed high concordance, interrater reliability, and internal
consistency, with weighted kappa values between 0.58 and 0.78 (95% CI, 0.39-0.78;
p < 0.001); intraclass correlation coefficient of 0.94 (95% CI, 0.94-0.98; p <
0.001), and Cronbach's alpha values of 0.94 and 0.95 (95% CI, 0.91-0.96; p <
0.001). The thumb CMC arthritis expectations survey score is convertible to an
overall score between 0 to 100 points calculated on the basis of the number of
expectations and the degree of improvement expected, with higher scores
indicating higher expectations. CONCLUSIONS: Patients with thumb CMC arthritis
volunteer a characteristic and quantifiable set of expectations. Using responses
recorded verbatim from patient interviews, a clinically relevant, valid, and
reliable expectations survey was developed that measures the physical and
psychosocial expectations of patients seeking treatment for CMC arthritis. The
survey provides a calculable score that can record patients' expectations.
Clinical application of this survey includes identification of factors that
influence fulfilment of these expectations. LEVEL OF EVIDENCE: Level II,
prospective study.
PMID- 26443778
TI - Reconstruction and Use of Microbial Metabolic Networks: the Core Escherichia coli
Metabolic Model as an Educational Guide.
AB - Biochemical network reconstructions have become popular tools in systems biology.
Metabolicnetwork reconstructions are biochemically, genetically, and genomically
(BiGG) structured databases of biochemical reactions and metabolites. They
contain information such as exact reaction stoichiometry, reaction reversibility,
and the relationships between genes, proteins, and reactions. Network
reconstructions have been used extensively to study the phenotypic behavior of
wild-type and mutant stains under a variety of conditions, linking genotypes with
phenotypes. Such phenotypic simulations have allowed for the prediction of growth
after genetic manipulations, prediction of growth phenotypes after adaptive
evolution, and prediction of essential genes. Additionally, because network
reconstructions are organism specific, they can be used to understand differences
between organisms of species in a functional context.There are different types of
reconstructions representing various types of biological networks (metabolic,
regulatory, transcription/translation). This chapter serves as an introduction to
metabolic and regulatory network reconstructions and models and gives a complete
description of the core Escherichia coli metabolic model. This model can be
analyzed in any computational format (such as MATLAB or Mathematica) based on the
information given in this chapter. The core E. coli model is a small-scale model
that can be used for educational purposes. It is meant to be used by senior
undergraduate and first-year graduate students learning about constraint-based
modeling and systems biology. This model has enough reactions and pathways to
enable interesting and insightful calculations, but it is also simple enough that
the results of such calculations can be understoodeasily.
PMID- 26443777
TI - The Efficacy of Some Commercially Available Insect Repellents for Aedes aegypti
(Diptera: Culicidae) and Aedes albopictus (Diptera: Culicidae).
AB - Reducing the number of host-vector interactions is an effective way to reduce the
spread of vector-borne diseases. Repellents are widely used to protect humans
from a variety of protozoans, viruses, and nematodes. DEET (N,N-Diethyl-meta
toluamide), a safe and effective repellent, was developed during World War II.
Fear of possible side effects of DEET has created a large market for "natural"
DEET-free repellents with a variety of active ingredients. We present a
comparative study on the efficacy of eight commercially available products, two
fragrances, and a vitamin B patch. The products were tested using a human hand as
attractant in a Y-tube olfactometer setup with Aedes aegypti (Linnaeus) and Aedes
albopictus (Skuse), both major human disease vectors. We found that Ae.
albopictus were generally less attracted to the test subject's hand compared with
Ae, aegypti. Repellents with DEET as active ingredient had a prominent repellency
effect over longer times and on both species. Repellents containing p-menthane
3,8-diol produced comparable results but for shorter time periods. Some of the
DEET-free products containing citronella or geraniol did not have any significant
repellency effect. Interestingly, the perfume we tested had a modest repellency
effect early after application, and the vitamin B patch had no effect on either
species. This study shows that the different active ingredients in commercially
available mosquito repellent products are not equivalent in terms of duration and
strength of repellency. Our results suggest that products containing DEET or p
menthane-3,8-diol have long-lasting repellent effects and therefore provide good
protection from mosquito-borne diseases.
PMID- 26443779
TI - Biogenesis and Membrane Targeting of Lipoproteins.
AB - Bacterial lipoproteins represent a unique class of membrane proteins, which are
anchored to membranes through triacyl chains attached to the amino-terminal
cysteine. They are involved in various functions localized in cell envelope.
Escherichia coli possesses more than 90 species of lipoproteins, most of which
are localized in the outer membrane, with others being in the inner membrane. All
lipoproteins are synthesized in the cytoplasm with an N-terminal signal peptide,
translocated across the inner membrane by the Sec translocon to the periplasmic
surface of the inner membrane, and converted to mature lipoproteins through
sequential reactions catalyzed by three lipoprotein-processing enzymes: Lgt,
LspA, and Lnt. The sorting of lipoproteins to the outer membrane requires a
system comprising five Lol proteins. An ATP-binding cassette transporter, LolCDE,
initiates the sorting by mediating the detachment of lipoproteins from the inner
membrane. Formation of the LolA-lipoprotein complex is coupled to this LolCDE
dependent release reaction. LolA accommodates the amino-terminal acyl chain of
lipoproteins in its hydrophobic cavity, thereby generating a hydrophilic complex
that can traverse the periplasmic space by diffusion. Lipoproteins are then
transferred to LolB on the outer membrane and anchored to the inner leaflet of
the outer membrane by the action of LolB. In contrast, since LolCDE does not
recognize lipoproteins possessing Asp at position +2, these lipoproteins remain
anchored to the inner membrane. Genes for Lol proteins are widely conserved among
gram-negative bacteria, and Lol-mediated outer membrane targeting of lipoproteins
is considered to be the general lipoprotein localization mechanism.
PMID- 26443780
TI - Solute and Ion Transport: Outer Membrane Pores and Receptors.
AB - Two membranes enclose Gram-negative bacteria-an inner membrane consisting of
phospholipid and an outer membrane having an asymmetric structure in which the
inner leaflet contains phospholipid and the outer leaflet consists primarily of
lipopolysaccharide. The impermeable nature of the outer membrane imposes a need
for numerous outer membrane pores and transporters to ferry substances in and out
of the cell. These outer membrane proteins have structures distinct from their
inner membrane counterparts and most often function without any discernable
energy source. In this chapter, we review the structures and functions of four
classes of outer membrane protein: general and specific porins, specific
transporters, TonB-dependent transporters, and export channels. While not an
exhaustive list, these classes exemplify small-molecule transport across the
outer membrane and illustrate the diversity of structures and functions found in
Gram-negative bacteria.
PMID- 26443781
TI - Biosynthesis of Riboflavin.
AB - The biosynthesis of riboflavin requires 1 equivalent of GTP and 2 equivalents of
ribulose phosphate. The first committed reactions of the convergent pathway are
catalyzed by GTP hydrolase II and 3,4-dihydroxy-2-butanone 4-phosphate synthase.
The initial reaction steps afford 5-amino-6-ribitylaminopyrimidine 5'-phosphate,
which needs to be dephosphorylated by a hitherto elusive hydrolase. The
dephosphorylated pyrimidine is condensed with the carbohydrate precursor, 3,4
dihydroxy-2-butanone 4-phosphate. The resulting 6,7-dimethyl-8-ribityllumazine
affords riboflavin by a mechanistically unique dismutation, i.e., by formation of
a pentacyclic dimer that is subsequently fragmented.
PMID- 26443782
TI - Type II Secretion in Escherichia coli.
AB - The type II secretion system (T2SS) is used by Escherichia coli and other gram
negative bacteria to translocate many proteins, including toxins and proteases,
across the outer membrane of the cell and into the extracellular space. Depending
on the bacterial species, between 12 and 15 genes have been identified that make
up a T2SS operon. T2SSs are widespread among gram-negative bacteria, and most E.
coli appear to possess one or two complete T2SS operons. Once expressed, the
multiple protein components that form the T2S system are localized in both the
inner and outer membranes, where they assemble into an apparatus that spans the
cell envelope. This apparatus supports the secretion of numerous virulence
factors; and therefore secretion via this pathway is regarded in many organisms
as a major virulence mechanism. Here, we review several of the known E. coli T2S
substrates that have proven to be critical for the survival and pathogenicity of
these bacteria. Recent structural and biochemical information is also reviewed
that has improved our current understanding of how the T2S apparatus functions;
also reviewed is the role that individual proteins play in this complex system.
PMID- 26443783
TI - DNA Helicases.
AB - DNA and RNA helicases are organized into six superfamilies of enzymes on the
basis of sequence alignments, biochemical data, and available crystal structures.
DNA helicases, members of which are found in each of the superfamilies, are an
essential group of motor proteins that unwind DNA duplexes into their component
single strands in a process that is coupled to the hydrolysis of nucleoside 5'
triphosphates. The purpose of this DNA unwinding is to provide nascent, single
stranded DNA (ssDNA) for the processes of DNA repair, replication, and
recombination. Not surprisingly, DNA helicases share common biochemical
properties that include the binding of single- and double-stranded DNA,
nucleoside 5'-triphosphate binding and hydrolysis, and nucleoside 5'-triphosphate
hydrolysis-coupled, polar unwinding of duplex DNA. These enzymes participate in
every aspect of DNA metabolism due to the requirement for transient separation of
small regions of the duplex genome into its component strands so that
replication, recombination, and repair can occur. In Escherichia coli, there are
currently twelve DNA helicases that perform a variety of tasks ranging from
simple strand separation at the replication fork to more sophisticated processes
in DNA repair and genetic recombination. In this chapter, the superfamily
classification, role(s) in DNA metabolism, effects of mutations, biochemical
analysis, oligomeric nature, and interacting partner proteins of each of the
twelve DNA helicases are discussed.
PMID- 26443784
TI - Escherichia coli and the French School of Molecular Biology.
AB - Andre Lwoff, Jacques Monod, and Francois Jacob, the leaders of the French school
of molecular biology, greatly contributed between 1937 and 1965 to its
development and triumph. The main discovery of Lwoff was the elucidation of the
mechanism of bacteriophage induction, the phenomenon of lysogeny, that led to the
model of genetic regulation uncovered later by Jacob and Monod. Working on
bacterial growth, Monod discovered in 1941 the phenomenon of diauxy and uncovered
the nature of enzyme induction. By combining genetic and biochemical approaches,
Monod brought to light the structure and functions of the Escherichia coli
lactose system, comprising the genes necessary for lactose metabolism, i.e., beta
galactosidase and lactose permease, a pump responsible for accumulation of
galactosides into the cells. An additional genetic factor (the i gene) determines
the inducibility and constitutivity of enzyme synthesis. Around the same time,
Francois Jacob and Elie Wollman dissected the main events of bacterial
conjugation that enabled them to construct a map of the E. coli chromosome and to
demonstrate its circularity. The genetic analysis of the lactose system led Monod
and Jacob to elucidate the mechanism of the regulation of gene expression and to
propose the operon model: a unit of coordinate transcription. One of the new
concepts that emerged from the operon model was messenger RNA. In 1963, Monod
developed one of the most elegant concepts of molecular biology, the theory of
allostery. In 1965, Lwoff, Monod and Jacob were awarded the Nobel Prize in
Physiology or Medicine.
PMID- 26443785
TI - Binding Protein-Dependent Uptake of Maltose into Cells via an ATP-Binding
Cassette Transporter.
AB - Maltose and maltodextrins are actively transported across the cytoplasmic
membrane of Escherichia coli and Salmonella by a periplasmic binding protein (BP)
dependent transport system. Since 1996, there have been many advances in the
understanding of the structure and mechanism of the maltose transporter, in the
assembly of the membrane-associated transporter complex, and in the mechanism of
regulation of transport both at the DNA and the protein level. The transporter
has been studied in detergent and reconstituted in liposome vesicles, and while
many features, including the ability of maltose-binding protein (MBP) to
stimulate ATPase activity, are retained in detergent, it has been noted that the
basal ATPase activity of the transporter is elevated in detergent compared with
liposomes. This review focuses on these recent developments, which have
culminated in a high resolution structure of MBP in a complex with the MalFGK2
transporter. While this review focuses on the maltose system, complementary work
has been carried out on many different ATP binding cassette (ABC) transporters,
all of which has contributed in important ways to the understanding of the
maltose transport system. The regulation of the maltose transport system, at the
DNA level, is implemented by the synergistic action of MalT and cAMP/CAP complex
and, at the protein level, by interactions of MalK with unphosphorylated EIIAglc,
a signal-transducing component of the phosphoenolpyruvate-glucose
phosphotransferase system.
PMID- 26443788
TI - The Tat Protein Export Pathway.
AB - Proteins that reside partially or completely outside the bacterial cytoplasm
require specialized pathways to facilitate their localization. Globular proteins
that function in the periplasm must be translocated across the hydrophobic
barrier of the inner membrane. While the Sec pathway transports proteins in a
predominantly unfolded conformation, the Tat pathway exports folded protein
substrates. Protein transport by the Tat machinery is powered solely by the
transmembrane proton gradient, and there is no requirement for nucleotide
triphosphate hydrolysis. Proteins are targeted to the Tat machinery by N-terminal
signal peptides that contain a consensus twin arginine motif. In Escherichia coli
and Salmonella there are approximately thirty proteins with twin arginine signal
peptides that are transported by the Tat pathway. The majority of these bind
complex redox cofactors such as iron sulfur clusters or the molybdopterin
cofactor. Here we describe what is known about Tat substrates in E. coli and
Salmonella, the function and mechanism of Tat protein export, and how the
cofactor insertion step is coordinated to ensure that only correctly assembled
substrates are targeted to the Tat machinery.
PMID- 26443789
TI - Bacterial Ion Channels.
AB - Bacterial ion channels were known, but only in special cases, such as outer
membrane porins in Escherichia coli and bacterial toxins that form pores in their
target (bacterial or mammalian) membranes. The exhaustive coverage provided by a
decade of bacterial genome sequencing has revealed that ion channels are actually
widespread in bacteria, with homologs of a broad range of mammalian channel
proteins coded throughout the bacterial and archaeal kingdoms. This review
discusses four groups of bacterial channels: porins, mechano-sensitive (MS)
channels, channel-forming toxins, and bacterial homologs of mammalian channels.
The outer membrane (OM) of gram-negative bacteria blocks access of essential
nutrients; to survive, the cell needs to provide a mechanism for nutrients to
penetrate the OM. Porin channels provide this access by forming large,
nonspecific aqueous pores in the OM that allow ions and vital nutrients to cross
it and enter the periplasm. MS channels act as emergency release valves, allowing
solutes to rapidly exit the cytoplasm and to dissipate the large osmotic
disparity between the internal and external environments. MS channels are
remarkable in that they do this by responding to forces exerted by the membrane
itself. Some bacteria produce toxic proteins that form pores in trans, attacking
and killing other organisms by virtue of their pore formation. The review focuses
on those bacterial toxins that kill other bacteria, specifically the class of
proteins called colicins. Colicins reveal the dangers of channel formation in the
plasma membrane, since they kill their targets with exactly that approach.
PMID- 26443787
TI - Type V Secretion: the Autotransporter and Two-Partner Secretion Pathways.
AB - The autotransporter and two-partner secretion (TPS) pathways are used by E. coli
and many other Gram-negative bacteria to delivervirulence factors into the
extracellular milieu.Autotransporters arecomprised of an N-terminal extracellular
("passenger") domain and a C-terminal beta barrel domain ("beta domain") that
anchors the protein to the outer membrane and facilitates passenger domain
secretion. In the TPS pathway, a secreted polypeptide ("exoprotein") is
coordinately expressed with an outer membrane protein that serves as a dedicated
transporter. Bothpathways are often grouped together under the heading "type V
secretion" because they have many features in common and are used for the
secretion of structurally related polypeptides, but it is likely that theyhave
distinct evolutionary origins. Although it was proposed many years ago that
autotransporterpassenger domains are transported across the outer membrane
through a channel formed by the covalently linked beta domain, there is
increasing evidence that additional factors are involved in the translocation
reaction. Furthermore, details of the mechanism of protein secretion through the
TPS pathway are only beginning to emerge. In this chapter I discussour current
understanding ofboth early and late steps in the biogenesis of polypeptides
secreted through type V pathways and current modelsofthe mechanism of secretion.
PMID- 26443790
TI - The Legacy of 20th Century Phage Research.
AB - The Golden Age of Phage Research, where phage was the favored material for
attacking many basic questions in molecular biology, lasted from about 1940 to
1970. The era was initiated by Ellis and Delbruck, whose analysis defined the
relevant parameters to measure in studying phage growth, and depended on the fact
that the contents of a plaque can comprise descendants of a single infecting
particle. It ended around 1970 because definitive methods had then become
available for answering the same questions in other systems. Some of the
accomplishments of phage research were the demonstration by Hershey and Chase
that the genetic material of phage T2 is largely composed of DNA, the
construction of linkage maps of T2 and T4 by Hershey and Rotman and their
extension to very short molecular distances by Benzer, and the isolation of
conditionally lethal mutants in T4 by Epstein et al. and in lambda by Campbell.
The dissection of the phage life cycle into causal chains was explored by Edgar
and Wood for T4 assembly and later in the regulation of lysogeny by Kaiser,
extended to the molecular level by Ptashne and others. Restriction/modification
was discovered in lambda by Bertani and Weigle, and the biochemical mechanism was
elucidated by Arber and by Smith.
PMID- 26443786
TI - Initiation of DNA Replication.
AB - In recent years it has become clear that complex regulatory circuits control the
initiation step of DNA replication by directing the assembly of a multicomponent
molecular machine (the orisome) that separates DNA strands and loads replicative
helicase at oriC, the unique chromosomal origin of replication. This chapter
discusses recent efforts to understand the regulated protein-DNA interactions
that are responsible for properly timed initiation of chromosome replication. It
reviews information about newly identified nucleotide sequence features within
Escherichia coli oriC and the new structural and biochemical attributes of the
bacterial initiator protein DnaA. It also discusses the coordinated mechanisms
that prevent improperly timed DNA replication. Identification of the genes that
encoded the initiators came from studies on temperature-sensitive, conditional
lethal mutants of E. coli, in which two DNA replication-defective phenotypes,
"immediate stop" mutants and "delayed stop" mutants, were identified. The
kinetics of the delayed stop mutants suggested that the defective gene products
were required specifically for the initiation step of DNA synthesis, and
subsequently, two genes, dnaA and dnaC, were identified. The DnaA protein is the
bacterial initiator, and in E. coli, the DnaC protein is required to load
replicative helicase. Regulation of DnaA accessibility to oriC, the ordered
assembly and disassembly of a multi-DnaA complex at oriC, and the means by which
DnaA unwinds oriC remain important questions to be answered and the chapter
discusses the current state of knowledge on these topics.
PMID- 26443791
TI - How are arrhythmias detected by implanted cardiac devices managed in Europe?
Results of the European Heart Rhythm Association Survey.
AB - The management of arrhythmias detected by implantable cardiac devices can be
challenging. There are no formal international guidelines to inform decision
making. The purpose of this European Heart Rhythm Association (EHRA) survey was
to assess the management of various clinical scenarios among members of the EHRA
electrophysiology research network. There were 49 responses to the questionnaire.
The survey responses were mainly (81%) from medium-high volume device implanting
centres, performing more than 200 total device implants per year. Clinical
scenarios were described focusing on four key areas: the implantation of
pacemakers for bradyarrhythmia detected on an implantable loop recorder (ILR),
the management of patients with ventricular arrhythmia detected by an ILR or
pacemaker, the management of atrial fibrillation in patients with pacemakers and
cardiac resynchronization therapy devices and the management of ventricular
tachycardia in patients with implantable cardioverter-defibrillators.
PMID- 26443792
TI - Brugada Syndrome with Early Repolarization masked by Complete Right Bundle-Branch
Block.
PMID- 26443793
TI - Authors' reply to Ozeke et al.
PMID- 26443795
TI - Healthicization and Lay Knowledge About Eating Practices in Two African American
Communities.
AB - In this manuscript, we expand upon sociological research in lay knowledge about
health and healthicization by examining socially mediated ways in which 40
African American adults in two communities acquired information about eating
practices. Participants employed a variety of socially informed information
seeking strategies. Many, but not all, used socially prescribed sources exhorting
them to maximize their own health and reported an amalgam of experiences
concerning their interpretation of healthist messages. Participants variously
accepted messages about healthy eating or engaged in strategies of micro
resistance that decentered and/or reinterpreted health promotion discourse.
Furthermore, participants used emic community-based resources including those
that prioritized familial engagement over individual responsibility in eating
practices or that drew upon alternative health practices. We discuss the
implications our work has for further research on healthicization and lay
knowledge about eating practices, in which community members are actively engaged
in meaning-making within local socio-structural contexts.
PMID- 26443796
TI - What Parents and Their Gay and Bisexual Sons Say About HIV Prevention.
AB - Despite ongoing prevention efforts, young gay and bisexual men (YGBM) accounted
for more than three fourths of all recent HIV infections. Furthermore, they
continue to engage in high-risk sexual behaviors at alarming rates. Nowadays,
families are beginning to emerge as important resources for these youth. However,
the viewpoints of YGBM and their families are largely missing from HIV prevention
research and intervention development. To address this gap, we solicited the
opinions of YGBM and their parents as to why YGBM engage in unsafe sex and what
might be done to help them avoid HIV. Participants discussed youth's sense of
invulnerability, sexual arousal, parental disapproval, and lack of societal
acceptance as contributors to unsafe sex. Participants called for gay-sensitive
sex education and community programming as well as increased societal acceptance.
Overall, respondents recommended interpersonal and structural-level interventions
that emphasized the importance of reducing stigma as a key component of HIV
prevention.
PMID- 26443794
TI - Recent insights into the biological functions of liver fatty acid binding protein
1.
AB - Over four decades have passed since liver fatty acid binding protein (FABP)1 was
first isolated. There are few protein families for which most of the complete
tertiary structures, binding properties, and tissue occurrences are described in
such detail and yet new functions are being uncovered for this protein. FABP1 is
known to be critical for fatty acid uptake and intracellular transport and also
has an important role in regulating lipid metabolism and cellular signaling
pathways. FABP1 is an important endogenous cytoprotectant, minimizing hepatocyte
oxidative damage and interfering with ischemia-reperfusion and other hepatic
injuries. The protein may be targeted for metabolic activation through the cross
talk among many transcriptional factors and their activating ligands. Deficiency
or malfunction of FABP1 has been reported in several diseases. FABP1 also
influences cell proliferation during liver regeneration and may be considered as
a prognostic factor for hepatic surgery. FABP1 binds and modulates the action of
many molecules such as fatty acids, heme, and other metalloporphyrins. The
ability to bind heme is another cytoprotective property and one that deserves
closer investigation. The role of FABP1 in substrate availability and in
protection from oxidative stress suggests that FABP1 plays a pivotal role during
intracellular bacterial/viral infections by reducing inflammation and the adverse
effects of starvation (energy deficiency).
PMID- 26443797
TI - Challenges in Exploratory Methods for Tuberculosis Research in South Africa.
AB - Haunted by a legacy of apartheid governance that left millions in material
poverty, South Africa has among the highest tuberculosis (TB) morbidity and
mortality rates in the world. Our Social Markers of TB research project shared a
vision of working with ethnographic research methods to understand TB-infected
persons, their families, care providers, and social networks. We argue that felt
and enacted TB stigma and the related HIV-TB stigma impaired our ability to
collect the necessary data for a full portrait of TB-infected persons and their
lived conditions. To circumvent this limitation, each researcher improvised and
augmented conventional anthropological methods with more creative, directed, and
at times destabilizing methods. We present three case studies as useful
illustrations of the complexities and challenges we encountered in our attempts
to conduct ethically sound TB research. We discuss the implications of our call
for "improvisation" for the politics of research and ethical oversight.
PMID- 26443798
TI - Childbearing Experiences Following an HIV Diagnosis in Iringa, Tanzania.
AB - People living with HIV (PLHIV) continue to have children after being diagnosed
with HIV, yet little research attention has been paid to actual lived
childbearing experiences of PLHIV post-HIV diagnosis. We interviewed 10 HIV
positive women and 11 HIV-positive men in Iringa, Tanzania, about their
experiences of conceiving and having children after being diagnosed with HIV. We
adopted an approach to data analysis based on grounded theory and phenomenology.
Participants' experiences were shaped by social and institutional factors. Some
participants reported pressures to bear children by partners and relatives,
whereas others reported negative reactions from others concerning their
pregnancies. Most participants had not discussed having children with a provider
before attempting to conceive. Some reported being reprimanded by health
providers for getting pregnant without seeking their advice. Consideration of
support systems and challenges surrounding the childbearing experiences of PLHIV
can help inform reproductive health interventions for those who desire children.
PMID- 26443800
TI - Feasibility of a Modified Biopsy Needle for Irreversible Electroporation Ablation
and Periprocedural Tissue Sampling.
AB - OBJECTIVES: To test the feasibility of modified biopsy needles as probes for
irreversible electroporation ablation and periprocedural biopsy. METHODS: Core
biopsy needles of 16-G/9-cm were customized to serve as experimental ablation
probes. Computed tomography-guided percutaneous irreversible electroporation was
performed in in vivo porcine kidneys with pairs of experimental (n = 10) or
standard probes (n = 10) using a single parameter set (1667 V/cm, ninety 100 us
pulses). Two biopsy samples were taken immediately following ablation using the
experimental probes (n = 20). Ablation outcomes were compared using computed
tomography, simulation, and histology. Biopsy and necropsy histology were
compared. RESULTS: Simulation-suggested ablations with experimental probes were
smaller than that with standard electrodes (455.23 vs 543.16 mm2), although both
exhibited similar shape. Computed tomography (standard: 556 +/- 61 mm2,
experimental: 515 +/- 67 mm2; P = .25) and histology (standard: 313 +/- 77 mm2,
experimental: 275 +/- 75 mm2; P = .29) indicated ablations with experimental
probes were not significantly different from the standard. Histopathology
indicated similar morphological changes in both groups. Biopsies from the
ablation zone yielded at least 1 core with sufficient tissue for analysis (11 of
the 20). CONCLUSIONS: A combined probe for irreversible electroporation ablation
and periprocedural tissue sampling from the ablation zone is feasible. Ablation
outcomes are comparable to those of standard electrodes.
PMID- 26443801
TI - Lupeol Induces Apoptosis and Cell Cycle Arrest of Human Osteosarcoma Cells
Through PI3K/AKT/mTOR Pathway.
AB - Lupeol, a dietary triterpene present in many fruits and medicinal plants, has
been reported to possess many pharmacological properties including anticancer
effect in vitro and in vivo However, the activity of lupeol against osteosarcoma
remains unclear. The present study is conducted to investigate the anticancer
activity and the underlying mechanisms of lupeol on human osteosarcoma cells
(MNNG/HOS and MG-63) in vitro and in vivo MNNG/HOS and MG-63 cells were treated
by lupeol and subjected to methyl thiazolyl tetrazolium analysis, Hoechst
staining, annexin V/propidium iodide double staining, cell cycle analysis, and
Western blot analysis. In addition, MNNG/HOS xenograft tumors were established in
female nude BALB/c mice, and lupeol was intravenously administered to evaluate
the anticancer capacity in vivo Our results showed that lupeol induced apoptosis
as well as cell cycle arrest in G0/G1 phase of MNNG/HOS and MG-63 cells in a dose
dependent manner in vitro Furthermore, the protein expression levels of phospho
phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT), p
p70S6K, and cyclin D1 were significantly downregulated, whereas the expression
levels of p21 and p27 were upregulated. These protein interactions may play a
pivotal role in the regulation of apoptosis and cell cycle arrest. More
importantly, our in vivo studies showed that administration of lupeol decreased
tumor growth in a dose-dependent manner and has no significant effect on the
function of liver and kidney. Taken together, our findings indicated that lupeol
can induce apoptosis as well as cell cycle arrest of human osteosarcoma cells
through phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway
and might offer a promising new approach in the effective treatment of
osteosarcoma.
PMID- 26443802
TI - Images in Vascular Medicine. A new or overlooked finding of varicose veins:
Ecchymosis.
PMID- 26443803
TI - Chronic cough revealing a giant thoraco-abdominal aortic aneurysm.
PMID- 26443804
TI - Recombinant Immunotoxin with T-cell Epitope Mutations That Greatly Reduce
Immunogenicity for Treatment of Mesothelin-Expressing Tumors.
AB - SS1P is a recombinant immunotoxin (RIT) that targets mesothelin. It consists of
an antimesothelin Fv fused to a portion of Pseudomonas exotoxin A. In clinical
studies, it has produced dramatic responses in patients with advanced
mesothelioma, when combined with immunosuppressive therapy so that several
treatment cycles could be given. Otherwise its activity is limited by its
immunogenicity. In this work, we describe the development and characterization of
LMB-T20, a highly potent RIT targeted at mesothelin-expressing cancers with low
immunogenicity due to removal of its eight T-cell epitopes. LMB-T20 was more
active than SS1P when tested on four different mesothelin-expressing cell lines
as well as on cells obtained from patients with mesothelioma. It also has potent
antitumor activity in mice, and has reduced immunogenicity as measured by
cytokine secretion assays. In conclusion, LMB-T20 is a favorable candidate for
evaluation in clinical trials due to its reduced immunogenicity and excellent
activity.
PMID- 26443805
TI - Genome-Wide Identification of a Methylation Gene Panel as a Prognostic Biomarker
in Nasopharyngeal Carcinoma.
AB - DNA methylation, the best known epigenetic marker, can be used as a prognostic
biomarker in many cancers. We examined DNA methylation status and survival in
nasopharyngeal carcinoma (NPC) patients. Aberrant DNA-methylated genes in 24 NPC
tissues and 24 noncancer nasopharyngitis biopsy tissues (NCNBT) were identified
using Illumina 450K BeadChip. Correlations between DNA methylation and clinical
outcomes were evaluated using bisulfite pyrosequencing in 454 NPC patients.
Genome-wide methylation analysis demonstrated that NPC tissues had distinct DNA
methylation patterns compared with NCNBT. Among all significant CpG sites, 2,173
CpG sites with beta change >= 0.2 (1,880 hypermethylated, 293 hypomethylated)
were identified (P < 0.05). A methylation gene panel comprising six
hypermethylated genes was constructed with the average Z-score method. Patients
in the training cohort with high methylation had poorer disease-free survival
[DFS, HR, 2.26; 95% confidence interval (CI), 1.28-4.01; P, 0.005] and overall
survival (OS, HR, 2.47; 95% CI, 1.30-4.71; P, 0.006) than those with low
methylation. There were similar results in the validation (DFS, HR, 2.07; 95% CI,
1.17-3.67; P, 0.013; OS, HR, 1.83; 95% CI, 1.01-3.31; P, 0.046) and independent
cohorts (DFS, HR, 1.94; 95% CI, 1.08-3.47; P, 0.026; OS, HR, 2.09; 95% CI, 1.10
3.98; P, 0.022). Analysis indicated that the methylation gene panel was an
independent prognostic factor. Furthermore, patients with low methylation had a
favorable response to concurrent chemotherapy with an improved DFS (P = 0.045)
and OS (P = 0.031), whereas patients with high methylation did not benefit from
concurrent chemotherapy. The six-hypermethylated gene panel was associated with
poor survival in patients with NPC, demonstrating its potential usefulness as a
prognostic biomarker to clinicians in NPC management.
PMID- 26443806
TI - Antitumor Activity of KW-2450 against Triple-Negative Breast Cancer by Inhibiting
Aurora A and B Kinases.
AB - Currently, no targeted drug is available for triple-negative breast cancer
(TNBC), an aggressive breast cancer that does not express estrogen receptor,
progesterone receptor, or HER2. TNBC has high mitotic activity, and, because
Aurora A and B mitotic kinases drive cell division and are overexpressed in
tumors with a high mitotic index, we hypothesized that inhibiting Aurora A and B
produces a significant antitumor effect in TNBC. We tested this hypothesis by
determining the antitumor effects of KW-2450, a multikinase inhibitor of both
Aurora A and B kinases. We observed significant inhibitory activities of KW-2450
on cell viability, apoptosis, colony formation in agar, and mammosphere formation
in TNBC cells. The growth of TNBC xenografts was significantly inhibited with KW
2450. In cell-cycle analysis, KW-2450 induced tetraploid accumulation followed by
apoptosis or surviving octaploid (8N) cells, depending on dose. These phenotypes
resembled those of Aurora B knockdown and complete pharmaceutical inhibition of
Aurora A. We demonstrated that 8N cells resulting from KW-2450 treatment depended
on the activation of mitogen-activated protein kinase kinase (MEK) for their
survival. When treated with the MEK inhibitor selumetinib combined with KW-2450,
compared with KW-2450 alone, the 8N cell population was significantly reduced and
apoptosis was increased. Indeed, this combination showed synergistic antitumor
effect in SUM149 TNBC xenografts. Collectively, Aurora A and B inhibition had a
significant antitumor effect against TNBC, and this antitumor effect was
maximized by the combination of selumetinib with Aurora A and B inhibition.
PMID- 26443807
TI - The impact of oxaliplatin on the gonads: from bedside to the bench.
AB - STUDY HYPOTHESIS: What is the impact of oxaliplatin on gonadal function? STUDY
FINDING: Our results in both the clinical and pre-clinical settings indicate that
oxaliplatin exerts moderate transient gonadal toxicity. WHAT IS KNOWN ALREADY:
Recent studies have indicated a significant increase in survivorship of
colorectal cancer patients of reproductive age, who may then face fertility
concerns. The impact of oxaliplatin on gonadal function is yet to be discovered.
STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Eleven female (<43 years) and eight
male (<45 years) patients recently diagnosed with colorectal cancer, who were
candidates for oxaliplatin-based protocol, were enrolled into the study. FSH,
estradiol, anti-Mullerian hormone (AMH) and menstrual pattern were measured in
female patients, whereas FSH, inhibin-B, testosterone, and steroid-hormone
binding globulin were measured in male patients. Hormones were measured at
baseline and 6 months post-treatment (last chemotherapy administration) in men
and women. In the animal model, pubertal mice were injected with oxaliplatin and
sacrificed 1 week, 1 month and 3 months later. Ovarian reserve was estimated by
serum AMH measurements. Testicular function was evaluated by serum inhibin-B and
sperm evaluation. Gonadal apoptosis (TUNEL), proliferation (Ki-67), repair
(PCNA), ovarian reserve (AMH) and testicular reserve (DAZL) were measured by
immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: In all women, AMH
decreased post-treatment, but remained above the detection limit in 9/11 patients
(P < 0.05). FSH was elevated, but did not exceed the premenopausal range in 9/11
patients. All patients remain menstruating or resumed menstruation post
treatment. In female mice oxaliplatin induced transient apoptosis at 1-month post
treatment. In men Inhibin-B was slightly reduced post-treatment. In male mice
oxaliplatin did not affect spermatozoa concentration, but was associated with
transient, moderate reductions of spermatocytes-spermatogonia numbers and
spermatozoa motility. LIMITATIONS, REASONS FOR CAUTION: Future prospective large
scale studies are warranted in order to affirm these outcomes. WIDER IMPLICATIONS
OF THE FINDINGS: Due to high survival rates of colorectal cancer patients of
reproductive age that were diagnosed at early stages of the disease, the issue of
treatment-induced gonadotoxicity gains significance. Since at the individual
level there might be a risk of infertility, a detailed discussion and referral to
fertility preservation prior to initiation of treatment is recommended.
Nevertheless, oxaliplatin-based protocols appear to be less gonadotoxic than
other chemotherapeutic protocols. LARGE SCALE DATA: None. STUDY FUNDING AND
COMPETING INTERESTS: This study was supported by the Israeli Science Foundation
(ISF) grant 13-1816 (I.B.-A.). There is no conflict of interest.
PMID- 26443808
TI - Brown-Vialetto-Van Laere syndrome: a 28-year follow-up.
PMID- 26443809
TI - 3'-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect
via Enhancing Prefrontal AMPA Receptor Signaling Pathway.
AB - BACKGROUND: The development of rapid and safe antidepressants for the treatment
of major depression is in urgent demand. Converging evidence suggests that
glutamatergic signaling seems to play important roles in the pathophysiology of
depression. METHODS: We studied the antidepressant effects of 3(')-deoxyadenosine
(3'-dA, Cordycepin) and the critical role of the alpha-amino-3-hydroxy-5-methyl-4
isoxazole propionic acid (AMPA) receptor in male CD-1 mice via behavioral and
biochemical experiments. After 3'-dA treatment, the phosphorylation and synaptic
localization of the AMPA receptors GluR1 and GluR2 were determined in the
prefrontal cortex (PFC) and hippocampus (HIP). The traditional antidepressant
imipramine was applied as a positive control. RESULTS: We found that an injection
of 3'-dA led to a rapid and robust antidepressant effect, which was significantly
faster and stronger than imipramine, after 45min in tail suspension and forced
swim tests. This antidepressant effect remained after 5 days of treatment with 3'
dA. Unlike the psycho-stimulants, 3'-dA did not show a hyperactive effect in the
open field test. After 45min or 5 days of treatment, 3'-dA enhanced GluR1 S845
phosphorylation in both the PFC and HIP. In addition, after 45min of treatment,
3'-dA significantly up-regulated GluR1 S845 phosphorylation and GluR1, but not
GluR2 levels, at the synapses in the PFC. After 5 days of treatment, 3'-dA
significantly enhanced GluR1 S845 phosphorylation and GluR1, but not GluR2, at
the synapses in the PFC and HIP. Moreover, the AMPA-specific antagonist GYKI
52466 was able to block the rapid antidepressant effects of 3'-dA. CONCLUSION:
This study identified 3'-dA as a novel rapid antidepressant with clinical
potential and multiple beneficial mechanisms, particularly in regulating the
prefrontal AMPA receptor signaling pathway.
PMID- 26443810
TI - Oxidative Stress and Response to Thymidylate Synthase-Targeted Antimetabolites.
AB - Thymidylate synthase (TYMS; EC 2.1.1.15) catalyzes the reductive methylation of
2'-deoxyuridine-5'-monophosphate (dUMP) by N(5),N(10)-methyhlenetetrahydrofolate,
forming dTMP for the maintenance of DNA replication and repair. Inhibitors of
TYMS have been widely used in the treatment of neoplastic disease. A number of
fluoropyrimidine and folate analogs have been developed that lead to inhibition
of the enzyme, resulting in dTMP deficiency and cell death. In the current study,
we have examined the role of oxidative stress in response to TYMS inhibitors. We
observed that intracellular reactive oxygen species (ROS) concentrations are
induced by these inhibitors and promote apoptosis. Activation of the enzyme NADPH
oxidase (NOX), which catalyzes one-electron reduction of O2 to generate
superoxide (O2 (?-)), is a significant source of increased ROS levels in drug
treated cells. However, gene expression profiling revealed a number of other
redox-related genes that may contribute to ROS generation. TYMS inhibitors also
induce a protective response, including activation of the transcription factor
nuclear factor E2-related factor 2 (NRF2), a critical mediator of defense against
oxidative and electrophilic stress. Our results show that exposure to TYMS
inhibitors induces oxidative stress that leads to cell death, while
simultaneously generating a protective response that may underlie resistance
against such death.
PMID- 26443811
TI - A Green's function method for simulation of time-dependent solute transport and
reaction in realistic microvascular geometries.
AB - A novel theoretical method is presented for simulating the spatially resolved
convective and diffusive transport of reacting solutes between microvascular
networks and the surrounding tissues. The method allows for efficient
computational solution of problems involving convection and non-linear binding of
solutes in blood flowing through microvascular networks with realistic 3D
geometries, coupled with transvascular exchange and diffusion and reaction in the
surrounding tissue space. The method is based on a Green's function approach, in
which the solute concentration distribution in the tissue is expressed as a sum
of fields generated by time-varying distributions of discrete sources and sinks.
As an example of the application of the method, the washout of an inert
diffusible tracer substance from a tissue region perfused by a network of
microvessels is simulated, showing its dependence on the solute's transvascular
permeability and tissue diffusivity. Exponential decay of the washout
concentration is predicted, with rate constants that are about 10-30% lower than
the rate constants for a tissue cylinder model with the same vessel length,
vessel surface area and blood flow rate per tissue volume.
PMID- 26443812
TI - The usage of a three-compartment model to investigate the metabolic differences
between hepatic reductase null and wild-type mice.
AB - 278: The Cytochrome P450 (CYP) system is involved in 90% of the human body's
interactions with xenobiotics and due to this, it has become an area of avid
research including the creation of transgenic mice. This paper proposes a three
compartment model which is used to explain the drug metabolism in the Hepatic
Reductase Null (HRN) mouse developed by the University of Dundee (Henderson, C.
J., Otto, D. M. E., Carrie, D., Magnuson, M. A., McLaren, A. W., Rosewell, I. and
Wolf, C. R. (2003) Inactivation of the hepatic cytochrome p450 system by
conditional deletion of hepatic cytochrome p450 reductase. J. Biol. Chem. , 13480
13486). The model is compared with a two-compartment model using experimental
data from studies using wild-type and HRN mice. This comparison allowed for
metabolic differences between the two types of mice to be isolated. The three
sets of drug data (Gefitinib, Midazolam and Thalidomide) showed that the
transgenic mouse has a decreased rate of metabolism.
PMID- 26443813
TI - Quality management and perceptions of teamwork and safety climate in European
hospitals.
AB - OBJECTIVE: This study aimed to investigate the associations of quality management
systems with teamwork and safety climate, and to describe and compare differences
in perceptions of teamwork climate and safety climate among clinical leaders and
frontline clinicians. METHOD: We used a multi-method, cross-sectional approach to
collect survey data of quality management systems and perceived teamwork and
safety climate. Our data analyses included descriptive and multilevel regression
methods. SETTING AND PARTICIPANTS: Data on implementation of quality management
system from seven European countries were evaluated including patient safety
culture surveys from 3622 clinical leaders and 4903 frontline clinicians. MAIN
OUTCOME MEASURES: Perceived teamwork and safety climate. RESULTS: Teamwork
climate was reported as positive by 67% of clinical leaders and 43% of frontline
clinicians. Safety climate was perceived as positive by 54% of clinical leaders
and 32% of frontline clinicians. We found positive associations between
implementation of quality management systems and teamwork and safety climate.
CONCLUSIONS: Our findings, which should be placed in a broader clinical quality
improvement context, point to the importance of quality management systems as a
supportive structural feature for promoting teamwork and safety climate. To gain
a deeper understanding of this association, further qualitative and quantitative
studies using longitudinally collected data are recommended. The study also
confirms that more clinical leaders than frontline clinicians have a positive
perception of teamwork and safety climate. Such differences should be accounted
for in daily clinical practice and when tailoring initiatives to improve teamwork
and safety climate.
PMID- 26443814
TI - Quality improvement and accountability in the Danish health care system.
AB - Denmark has unique opportunities for quality measurement and benchmarking since
Denmark has well-developed health registries and unique patient identifier that
allow all registries to include patient-level data and combine data into
sophisticated quality performance monitoring. Over decades, Denmark has developed
and implemented national quality and patient safety initiatives in the healthcare
system in terms of national clinical guidelines, performance and outcome
measurement integrated in clinical databases for important diseases and clinical
conditions, measurement of patient experiences, reporting of adverse events,
national handling of patient complaints, national accreditation and public
disclosure of all data on the quality of care. Over the years, Denmark has worked
up a progressive and transparent just culture in quality management; the
different actors at the different levels of the healthcare system are mutually
attentive and responsive in a coordinated effort for quality of the healthcare
services. At national, regional, local and hospital level, it is mandatory to
participate in the quality initiatives and to use data and results for quality
management, quality improvement, transparency in health care and accountability.
To further develop the Danish governance model, it is important to expand the
model to the primary care sector. Furthermore, a national quality health
programme 2015-18 recently launched by the government supports a new development
in health care focusing upon delivering high-quality health care-high quality is
defined by results of value to the patients.
PMID- 26443815
TI - Population experiences of primary care in 11 Organization for Economic
Cooperation and Development countries.
AB - OBJECTIVE: To develop a measure of individual user assessments of primary care
and test its association with health system performance and quality indicators.
DESIGN: Cross-sectional analysis of secondary survey data collected in 2013.
SETTING: Australia, Canada, France, Germany, Netherlands, New Zealand, Norway,
Sweden, Switzerland, the UK and the USA. STUDY PARTICIPANTS: 20 045 respondents.
MAIN OUTCOME MEASURES: Individual report of financial protection (out of pocket
expenses over USD 1000), lack of receipt of appropriate/timely care (use of the
emergency room in the past 2 years, having consulted three of more doctors in the
past year) and clinical prevention (blood pressure check in past year,
cholesterol checked in the past 5 years, receipt of influenza vaccination in past
year and report of any medical error). METHODS: A score of users' primary care
experiences was constructed from 14 individual survey questions. Multivariable
Poisson and augmented inverse-probability weighted regression assess the
relationship between the primary care experience score and outcomes. RESULTS:
Countries differed regarding the proportion of the population experiencing
problems with primary care. In analyses controlling for age, sex, health status,
chronic disease, income level and health insurance, users experiencing poorer
primary care were significantly more likely to report significant out of pocket
expenses, emergency room use in the past 2 years, having consulted more than
three doctors in the past year, lower likelihood of blood pressure or cholesterol
screening, an annual flu shot and higher reports of medical error. CONCLUSIONS:
The measure of individual primary care experience can be used to differentiate
among different country's primary care approaches and is strongly associated with
overall health system performance and quality indicators.
PMID- 26443816
TI - Missense mutations of PBP2a are associated with reduced susceptibility to
ceftaroline and ceftobiprole in African MRSA.
AB - OBJECTIVES: Ceftaroline and ceftobiprole are new cephalosporins, which are active
against MRSA by inhibiting PBP2a. Recently, high rates of resistance to
ceftaroline were reported from Ghana. The objective of this study was to assess
rates of resistance to ceftaroline and ceftobiprole in MRSA from Africa and to
describe potential missense mutations of PBP2a. METHODS: MRSA isolates derived
from Staphylococcus aureus colonization (n = 37) and infection (n = 23) and were
collected in Cote d'Ivoire (n = 17), DR Congo (n = 6), Gabon (n = 21) and Nigeria
(n = 16). The MICs were determined by the broth microdilution method. The mecA
gene was sequenced and missense mutations were associated with the corresponding
MLST ST. RESULTS: In total, 16.7% (n = 10) and 15% (n = 9) of isolates were
resistant to ceftaroline and ceftobiprole, respectively. The corresponding MICs
of ceftaroline and ceftobiprole correlated significantly (r = 0.92). Isolates
belonging to ST241 harboured a triple mutation of PBP2a (N146K-N204K-G246E),
which was associated with high rates of resistance to ceftaroline (90.9%) and
ceftobiprole (81.8%). CONCLUSIONS: Resistances to ceftaroline and ceftobiprole
were only detected in Nigeria and were associated with ST241 and a triple
mutation of PBP2a.
PMID- 26443817
TI - Chaperome screening leads to identification of Grp94/Gp96 and FKBP4/52 as
modulators of the alpha-synuclein-elicited immune response.
AB - We have investigated the potential role of molecular chaperones as modulators of
the immune response by using alpha-synuclein (alphaSyn) as an aggregation-prone
model protein. We first performed an in vitro immunoscreening with 21 preselected
candidate chaperones and selected 2 from this set as displaying immunological
activity with differential profiles, Grp94/Gp96 and FKBP4/52. We then immunized
mice with both chaperone/alpha-synuclein combinations using monomeric or
oligomeric alpha-synuclein (MalphaSyn or OalphaSyn, respectively), and we
characterized the immune response generated in each case. We found that Grp94
promoted alphaSyn-specific T-helper (Th)1/Th17 and IgG1 antibody responses (up to
a 3-fold increase) with MalphaSyn and OalphaSyn, respectively, coupled to a Th2
type general phenotype (generating 2.5-fold higher IgG1/IgG2 levels). In
addition, we observed that FKBP4 favored a Th1-skewed phenotype with MalphaSyn
but strongly supported a Th2-type phenotype with OalphaSyn (with a 3-fold higher
IL-10/IFN-gamma serum levels). Importantly, results from adoptive transfer of
splenocytes from immunized animals in a Parkinson's disease mouse model indicates
that these effects are robust, stable in time, and physiologically relevant.
Taken together, Grp94 and FKBP4 are able to generate differential immune
responses to alpha-synuclein-based immunizations, depending both on the nature of
the chaperone and on the aggregation state of alpha-synuclein. Our work reveals
that several chaperones are potential modulators of the immune response and
suggests that different chaperones could be exploited to redirect the amyloid
elicited immunity both for basic studies of the immunological processes
associated with neurodegeneration and for immunotherapy of pathologies associated
with protein misfolding and aggregation.
PMID- 26443818
TI - Biomedical science postdocs: an end to the era of expansion.
AB - After >3 decades of steady growth, the number of biological and medical science
postdoctorates at doctoral degree-granting institutions recently began to
decline. From 2010 through 2013, the most recent survey years, the postdoctoral
population decreased from 40,970 to 38,719, a loss of 5.5%. This decline
represents a notable departure from the previous long-standing increases in the
number of postdoctorates in the biomedical workforce. The rate of contraction
appears to be accelerating in the most recent survey years, and this has
important implications for the biomedical workforce.
PMID- 26443819
TI - Scleraxis is required for the development of a functional tendon enthesis.
AB - The attachment of dissimilar materials is a major engineering challenge, yet this
challenge is seemingly overcome in biology. This study aimed to determine how the
transcription factor Scleraxis (Scx) influences the development and maturation of
the tendon-to-bone attachment (enthesis). Mice with conditional knockout (cKO)
for Scx (Scx(flx/-), Prx1Cre(+)) and wild-type [(WT) Scx(flx/+) or Scx(flx/flx)]
littermates were killed at postnatal days 7-56 (P7-P56). Enthesis morphometry,
histology, and collagen alignment were investigated throughout postnatal growth.
Enthesis tensile mechanical properties were also assessed. Laser microdissection
of distinct musculoskeletal tissues was performed at P7 for WT, cKO, and muscle
unloaded (botulinum toxin A treated) attachments for quantitative PCR. cKO mice
were smaller, with altered bone shape and impaired enthesis morphology,
morphometry, and organization. Structural alterations led to altered mechanical
properties; cKO entheses demonstrated reduced strength and stiffness. In P7
attachments, cKO mice had reduced expression of transforming growth factor (TGF)
superfamily genes in fibrocartilage compared with WT mice. In conclusion,
deletion of Scx led to impairments in enthesis structure, which translated into
impaired functional (i.e., mechanical) outcomes. These changes may be driven by
transient signaling cues from mechanical loading and growth factors.
PMID- 26443821
TI - Site-specific recombination in the chicken genome using Flipase recombinase
mediated cassette exchange.
AB - Targeted genome recombination has been applied in diverse research fields and has
a wide range of possible applications. In particular, the discovery of specific
loci in the genome that support robust and ubiquitous expression of integrated
genes and the development of genome-editing technology have facilitated rapid
advances in various scientific areas. In this study, we produced transgenic (TG)
chickens that can induce recombinase-mediated gene cassette exchange (RMCE), one
of the site-specific recombination technologies, and confirmed RMCE in TG chicken
derived cells. As a result, we established TG chicken lines that have, Flipase
(Flp) recognition target (FRT) pairs in the chicken genome, mediated by piggyBac
transposition. The transgene integration patterns were diverse in each TG chicken
line, and the integration diversity resulted in diverse levels of expression of
exogenous genes in each tissue of the TG chickens. In addition, the replaced gene
cassette was expressed successfully and maintained by RMCE in the FRT predominant
loci of TG chicken-derived cells. These results indicate that targeted genome
recombination technology with RMCE could be adaptable to TG chicken models and
that the technology would be applicable to specific gene regulation by cis
element insertion and customized expression of functional proteins at predicted
levels without epigenetic influence.
PMID- 26443820
TI - Basement membrane stiffening promotes retinal endothelial activation associated
with diabetes.
AB - Endothelial activation is a hallmark of the high-glucose (HG)-induced retinal
inflammation associated with diabetic retinopathy (DR). However, precisely how HG
induces retinal endothelial activation is not fully understood. We hypothesized
that HG-induced up-regulation of lysyl oxidase (LOX), a collagen-cross-linking
enzyme, in retinal capillary endothelial cells (ECs) enhances subendothelial
basement membrane (BM) stiffness, which, in turn, promotes retinal EC activation.
Diabetic C57BL/6 mice exhibiting a 70 and 50% increase in retinal intercellular
adhesion molecule (ICAM)-1 expression and leukocyte accumulation, respectively,
demonstrated a 2-fold increase in the levels of BM collagen IV and LOX, key
determinants of capillary BM stiffness. Using atomic force microscopy, we
confirmed that HG significantly enhances LOX-dependent subendothelial matrix
stiffness in vitro, which correlated with an ~2.5-fold increase in endothelial
ICAM-1 expression, a 4-fold greater monocyte-EC adhesion, and an ~2-fold
alteration in endothelial NO (decrease) and NF-kappaB activation (increase).
Inhibition of LOX-dependent subendothelial matrix stiffening alone suppressed HG
induced retinal EC activation. Finally, using synthetic matrices of tunable
stiffness, we demonstrated that subendothelial matrix stiffening is necessary and
sufficient to promote EC activation. These findings implicate BM stiffening as a
critical determinant of HG-induced retinal EC activation and provide a rationale
for examining BM stiffness and underlying mechanotransduction pathways as
therapeutic targets for diabetic retinopathy.
PMID- 26443822
TI - Stretch regulates expression and binding of chymotrypsin-like elastase 1 in the
postnatal lung.
AB - Lung stretch is critical for normal lung development and for compensatory lung
growth after pneumonectomy (PNX), but the mechanisms by which strain induces
matrix remodeling are unclear. Our prior work demonstrated an association of
chymotrypsin-like elastase 1 (Cela1) with lung elastin remodeling, and that
strain triggered a near-instantaneous elastin-remodeling response. We sought to
determine whether stretch regulates Cela1 expression and Cela1 binding to lung
elastin. In C57BL/6J mice, Cela1 protein increased 176-fold during lung
morphogenesis. Cela1 was covalently bound to serpin peptidase inhibitor, clade A,
member 1, resulting in a higher molecular mass in lung homogenate compared to
pancreas homogenate. Post-PNX, Cela1 mRNA increased 6-fold, protein 3-fold, and
Cela1-positive cells 2-fold. Cela1 was expressed predominantly in alveolar type
II cells in the embryonic lung and predominantly in CD90-positive lung
fibroblasts postnatally. During compensatory lung growth, Cela1 expression was
induced in nonproliferative mesenchymal cells. In ex vivo mouse lung sections,
stretch increased Cela1 binding to lung tissue by 46%. Competitive inhibition
with soluble elastin completely abrogated this increase. Areas of stretch-induced
elastase activity and Cela1 binding colocalized. The stretch-dependent expression
and binding kinetics of Cela1 indicate an important role in stretch-dependent
remodeling of the peripheral lung during development and regeneration.
PMID- 26443823
TI - Imaging rhodopsin degeneration in vivo in a new model of ocular ischemia in
living mice.
AB - Delivery of antibodies to monitor key biomarkers of retinopathy in vivo
represents a significant challenge because living cells do not take up
immunoglobulins to cellular antigens. We met this challenge by developing novel
contrast agents for retinopathy, which we used with magnetic resonance imaging
(MRI). Biotinylated rabbit polyclonal to chick IgY (rIgPxcIgY) and
phosphorylthioate-modified oligoDNA (sODN) with random sequence (bio-sODN-Ran)
were conjugated with NeutrAvidin-activated superparamagnetic iron oxide
nanoparticles (SPION). The resulting Ran-SPION-rIgPxcIgY carries chick polyclonal
to microtubule-associated protein 2 (MAP2) as Ran-SPION-rIgP/cIgY-MAP2, or to
rhodopsin (Rho) as anti-Rho-SPION-Ran. We examined the uptake of Ran-SPION
rIgP/cIgY-MAP2 or SPION-rIgP/cIgY-MAP2 in normal C57black6 mice (n = 3 each, 40
MUg/kg, i.c.v.); we found retention of Ran-SPION-rIgP/cIgY-MAP2 using molecular
contrast-enhanced MRI in vivo and validated neuronal uptake using Cy5-goat
IgPxcIgY ex vivo. Applying this novel method to monitor retinopathy in a
bilateral carotid artery occlusion-induced ocular ischemia, we observed pericytes
(at d 2, using Gd-nestin, by eyedrop solution), significant photoreceptor
degeneration (at d 20, using anti-Rho-SPION-Ran, eyedrops, P = 0.03, Student's t
test), and gliosis in Muller cells (at 6 mo, using SPION-glial fibrillary acidic
protein administered by intraperitoneal injection) in surviving mice (n >= 5).
Molecular contrast-enhanced MRI results were confirmed by optical and electron
microscopy. We conclude that chimera and molecular contrast-enhanced MRI provide
sufficient sensitivity for monitoring retinopathy and for theranostic
applications.
PMID- 26443824
TI - CX3CR1 deficiency delays acute skeletal muscle injury repair by impairing
macrophage functions.
AB - Adequate inflammatory response predominated by macrophage infiltration is
essential to acute skeletal muscle injury repair. The majority of intramuscular
macrophages express the chemokine receptor CX3CR1. We studied the role of CX3CR1
in regulating intramuscular macrophage number and function in acute injury repair
by using a loss-of-function approach. Muscle injury repair was delayed in
CX3CR1(GFP/GFP) mice as compared with wild-type (WT) controls. CX3CR1 was
predominantly expressed by macrophages but not by myogenic cells or capillary
endothelia cells in injured muscles. Intramuscular macrophage number and subset
composition were not altered by CX3CR1 deficiency. Intramuscular macrophage
phagocytosis function was impaired by CX3CR1 deficiency as demonstrated by
increased number of necrotic fibers (+115%) and percentage of necrotic area
(+204%) at 7 d, increased number of intramuscular neutrophils at 3 (+89%) but not
1 d, reduced number of phagocytosing macrophages (-12%) and phagocytosed beads
within macrophages (-15%) in CX3CR1(GFP/GFP) mice as compared with WT controls.
The mRNA expression of CD36 (-50%), CD14 (-43%), IGF-1 (-53%), and IL-6 (-40%)
was reduced in CX3CR1-deficient macrophages as compared with WT controls. We
conclude that CX3CR1 is important to acute skeletal muscle injury repair by
regulating macrophage phagocytosis function and trophic growth factor production.
PMID- 26443825
TI - Plasmodium actin is incompletely folded by heterologous protein-folding machinery
and likely requires the native Plasmodium chaperonin complex to enter a mature
functional state.
AB - Actin filament turnover underpins several processes in the life cycle of the
malaria parasite, Plasmodium falciparum. Polymerization and depolymerization are
especially important for gliding motility, a substrate-dependent form of cell
movement that underpins the protozoan parasite's ability to disseminate and
invade host cells. To date, given difficulties in extraction of native actins
directly from parasites, much of our biochemical understanding of malarial actin
has instead relied on recombinant protein extracted and purified from
heterologous protein expression systems. Here, using in vitro transcription
translation methodologies and quantitative protein-binding assays, we explored
the folding state of heterologously expressed P. falciparum actin 1 (PfACTI) with
the aim of assessing the reliability of current recombinant-protein-based data.
We demonstrate that PfACTI, when expressed in non-native systems, is capable of
binding to and release from bacterial, yeast, and mammalian chaperonin complexes
but appears to be incompletely folded. Characterization of the native Plasmodium
folding machinery in silico, the chaperonin containing t-complex protein-1
complex, highlights key divergences between the different chaperonin systems that
likely underpins this incomplete folded state. These results highlight the
importance of characterizing actin's folded state and raise concerns about the
interpretation of actin polymerization kinetics based solely on protein derived
from heterologous expression systems.
PMID- 26443827
TI - Letter by Woodworth and Simard Regarding Article, "Outcome Following
Decompressive Hemicraniectomy for Malignant Cerebral Infarction: Ethical
Considerations".
PMID- 26443826
TI - Hydrogel biophysical properties instruct coculture-mediated osteogenic potential.
AB - Cell-based approaches for bone formation require instructional cues from the
surrounding environment. As an alternative to pharmacological strategies or
transplanting single cell populations, one approach is to coimplant populations
that can establish a new vasculature and differentiate to bone-forming
osteoblasts. Mesenchymal stem/stromal cells (MSCs) possess osteogenic potential
and produce numerous angiogenic growth factors. Endothelial colony-forming cells
(ECFCs) are a subpopulation of endothelial progenitor cells capable of
vasculogenesis in vivo and may provide endogenous cues to support MSC function.
We investigated the contribution of the carrier biophysical properties to
instruct entrapped human MSCs and ECFCs to simultaneously promote their
osteogenic and proangiogenic potential. Compared with gels containing MSCs alone,
fibrin gels engineered with increased compressive stiffness simultaneously
increased the osteogenic and proangiogenic potential of entrapped cocultured
cells. ECFCs produced bone morphogenetic protein-2 (BMP-2), a potent
osteoinductive molecule, and increases in BMP-2 secretion correlated with gel
stiffness. Coculture of MSCs with ECFCs transduced to knockdown BMP-2 production
abrogated the osteogenic response to levels observed with MSCs alone. These
results demonstrate that physical properties of engineered hydrogels modulate the
function of cocultured cells in the absence of inductive cues, thus increasing
the translational potential of coimplantation to speed bone formation and repair.
PMID- 26443830
TI - Letter by Avasarala Regarding Article, "2015 AHA/ASA Focused Update of the 2013
Guidelines for the Early Management of Patients With Acute Ischemic Stroke
Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From
the American Heart Association/American Stroke Association".
PMID- 26443828
TI - Differences in Common Genetic Predisposition to Ischemic Stroke by Age and Sex.
AB - BACKGROUND AND PURPOSE: Evidence from epidemiological studies points to
differences in factors predisposing to stroke by age and sex. Whether these arise
because of different genetic influences remained untested. Here, we use data from
4 genome-wide association data sets to study the relationship between genetic
influence on stroke with both age and sex. METHODS: Using genomic-relatedness
matrix restricted maximum likelihood methods, we performed 4 analyses: (1) we
calculated the genetic correlation between groups divided by age and (2) by sex,
(3) we calculated the heritability of age-at-stroke-onset, and (4) we evaluated
the evidence that heritability of stroke is greater in women than in men.
RESULTS: We found that genetic factors influence age at stroke onset (h2
[SE]=18.0 [6.8]; P=0.0038), with a trend toward a stronger influence in women
(women: h2 [SE]=21.6 [3.5]; Men: h2 [SE]=13.9 [2.8]). Although a moderate
proportion of genetic factors was shared between sexes (rG [SE]=0.68 [0.16]) and
between younger and older cases (rG [SE]=0.70 [0.17]), there was evidence to
suggest that there are genetic susceptibility factors that are specific to sex
(P=0.037) and to younger or older groups (P=0.056), particularly for women
(P=0.0068). Finally, we found a trend toward higher heritability of stroke in
women although this was not significantly greater than in men (P=0.084).
CONCLUSIONS: Our results indicate that there are genetic factors that are either
unique to or have a different effect between younger and older age groups and
between women and men. Performing large, well-powered genome-wide association
study analyses in these groups is likely to uncover further associations.
PMID- 26443831
TI - Response to Letter Regarding Article, "Outcome Following Decompressive
Hemicraniectomy for Malignant Cerebral Infarction: Ethical Considerations".
PMID- 26443829
TI - Effects of Induced Hypertension on Cerebral Perfusion in Delayed Cerebral
Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.
AB - BACKGROUND AND PURPOSE: The presumed effectiveness of induced hypertension for
treating delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage is
based on uncontrolled case-series only. We assessed the effect of induced
hypertension on cerebral blood flow (CBF) in aneurysmal subarachnoid hemorrhage
patients with delayed cerebral ischemia in a randomized clinical trial. METHODS:
Aneurysmal subarachnoid hemorrhage patients were randomized to induced or no
induced hypertension (control group) at delayed cerebral ischemia onset. CBF was
assessed, blinded for treatment allocation, with computed tomographic perfusion
in standardized predefined regions at delayed cerebral ischemia onset and after
24 to 36 hours of study treatment. Mean arterial blood pressure was compared
between groups (linear mixed model). The primary outcome measure was the
difference in change in overall CBF (Mann-Whitney U test). RESULTS: Mean arterial
blood pressure was, on average, 12 mm Hg (95% confidence interval, 8.6-14.5)
higher in the hypertension group (n=12) than in the control group (n=13). Change
in overall CBF (mL/100g per s) was -8.5 (range, -42 to 30) in the control group
and 0.1 (range, -31-43) in the hypertension group (P=0.25). CONCLUSIONS: Change
in overall CBF did not differ to a statistically significant extent between the
groups. Based on our results, 225 to 250 patients per group are needed to find a
statistically significant difference in change in overall CBF between induced
hypertension and no hypertension. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT0161323.
PMID- 26443832
TI - Alteplase Reduces Downstream Microvascular Thrombosis and Improves the Benefit of
Large Artery Recanalization in Stroke.
AB - BACKGROUND AND PURPOSE: Downstream microvascular thrombosis (DMT) is known to be
a contributing factor to incomplete reperfusion in acute ischemic stroke. The aim
of this study was to determine the timing of DMT with intravital imaging and to
test the hypothesis that intravenous alteplase infusion could reduce DMT in a
transient middle cerebral artery occlusion (MCAO) rat stroke model. METHODS: Rats
were subjected to 60-minute transient MCAO. Alteplase (10 mg/kg) was administered
30 minutes after the beginning of MCAO. Real-time intravital fluorescence
microscopy through a dura-sparing craniotomy was used to visualize circulating
blood cells and fibrinogen. Cerebral microvessel patency was quantitatively
evaluated by fluorescein isothiocyanate-dextran perfusion. RESULTS: Immediately
after MCAO, platelet and leukocyte accumulation were observed mostly in the
venous compartment. Within 30 minutes after MCAO, microthrombi and parietal
fibrin deposits were detected in postcapillary microvessels. Alteplase treatment
significantly (P=0.006) reduced infarct volume and increased the percentage of
perfused vessels during MCAO (P=0.02) compared with saline. Plasma levels of
fibrinogen from alteplase-treated rats showed a rapid and profound
hypofibrinogenemia. In vitro platelet aggregation demonstrated that alteplase
reduced platelet aggregation (P=0.0001) and facilitated platelet disaggregation
(P=0.001). These effects were reversible in the presence of exogenous fibrinogen.
CONCLUSIONS: Our data demonstrate that DMT is an early phenomenon initiated
before recanalization. We further show that alteplase-dependent maintenance of
downstream perfusion during MCAO improves acute ischemic stroke outcome through a
fibrinogen-dependent platelet aggregation reduction. Our results indicate that
early targeting of DMT represents a therapeutic strategy to improve the benefit
of large artery recanalization in acute ischemic stroke.
PMID- 26443833
TI - Quantifying the Benefit of Prehospital Rapid Treatment in Acute Stroke: Benchmark
for Future Innovative Clinical Trials.
AB - BACKGROUND AND PURPOSE: In acute ischemic stroke, time from onset to tissue-type
plasminogen activator treatment (OTT) is a major determinant of outcome. To
reduce OTT, clinical trials have been undertaken evaluating prehospital cerebral
imaging with mobile computed tomographic scanners. Furthermore, blood biomarkers
may allow rapid differentiation between ischemic stroke and intracerebral
hemorrhage before hospital admission. How such treatment strategies translate
into clinical benefit has not been specifically evaluated. METHODS: We
constructed decision models to estimate the net clinical benefit yielded by
shorter OTT. In different scenarios, we estimated the proportion of patients with
favorable outcome and the average quality of life. RESULTS: An OTT reduction of
60 minutes increases the probability of favorable outcome by 6.6% in a mixed
stroke population. For comparison, the average effect of tissue-type plasminogen
activator itself is 7.0%. Prehospital mobile computed tomography gaining 25 to 40
minutes increases the probability of favorable outcome by 3.0% to 4.6%. The
additional benefit of prehospital computed tomography to deliver patients with
large vessel occlusion directly to endovascular treatment centers increases the
probability of favorable outcome by another 0.2% to 1.0%. A blood test
discriminating ischemic stroke and intracerebral hemorrhage may beneficially
substitute brain scan before tissue-type plasminogen activator if >32 to 40
minutes are gained and if sensitivity for intracerebral hemorrhage is >75% to
80%. CONCLUSIONS: Reducing the OTT has robust beneficial effects for acute stroke
patients. Prehospital tissue-type plasminogen activator treatment without brain
imaging may become conceivable under several preconditions, including a point-of
care test with >75% to 80% sensitivity to detect intracerebral hemorrhage and a
time gain of >32 to 40 minutes. Ethical implications remain to be addressed.
PMID- 26443834
TI - Genetic analysis of environmental strains of the plant pathogen Phytophthora
capsici reveals heterogeneous repertoire of effectors and possible effector
evolution via genomic island.
AB - Phytophthora capsici is a virulent oomycete pathogen of many vegetable crops.
Recently, it has been demonstrated that the recognition of the RXLR effector
AVR3a1 of P. capsici (PcAVR3a1) triggers a hypersensitive response and plays a
critical role in mediating non-host resistance. Here, we analyzed the occurrence
of PcAVR3a1 in 57 isolates of P. capsici derived from globe squash, eggplant,
tomato and bell pepper cocultivated in a small geographical area. The occurrence
of PcAVR3a1 in environmental strains of P. capsici was confirmed by PCR in only
21 of these pathogen isolates. To understand the presence-absence pattern of
PcAVR3a1 in environmental strains, the flanking region of this gene was
sequenced. PcAVR3a1 was found within a genetic element that we named PcAVR3a1-GI
(PcAVR3a1 genomic island). PcAVR3a1-GI was flanked by a 22-bp direct repeat,
which is related to its site-specific recombination site. In addition to the
PcAVR3a1 gene, PcAVR3a1-GI also encoded a phage integrase probably associated
with the excision and integration of this mobile element. Exposure to plant
induced the presence of an episomal circular intermediate of PcAVR3a1-GI,
indicating that this mobile element is functional. Collectively, these findings
provide evidence of PcAVR3a1 evolution via mobile elements in environmental
strains of Phytophthora.
PMID- 26443835
TI - Rationale design of quorum-quenching peptides that target the VirSR system of
Clostridium perfringens.
AB - In Clostridium perfringens, a 5-membered thiolactone peptide acts as an
autoinducing peptide (AIPCp) to activate the VirSR two-component signal
transduction system, which in turn controls the expression of genes encoding
multiple toxins, including alpha, theta and kappa. To develop anti-pathogenic
agents against virulent C. perfringens, quorum-quenching peptides were rationally
designed based on the structure-activity relationship (SAR) data on AIPCp.
Alanine scanning study of AIPCp suggested that Trp(3) and Phe(4) are involved in
receptor binding and activation, respectively. On the basis of the SAR, we
designed two quorum-quenching peptides with different modes of action: Z-AIPCp
L2A/T5A (partial agonist) and Z-AIPCp-F4A/T5S (partial antagonist). Both peptides
significantly attenuated transcription of theta toxin gene (pfoA) in a virulent
strain of C. perfringens with IC50 = 0.32 and 0.72 MUM, respectively.
PMID- 26443836
TI - Different roles of the C-terminal end of Stx1A and Stx2A for AB5 complex
integrity and retrograde transport of Stx in HeLa cells.
AB - Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) differ regarding receptor affinity,
cellular toxicity and clinical outcome. To this date, it is not clarified in
detail why the subtypes display these differences. Even though the crystal
structures of Stx1 and Stx2 share overall similarities, significant differences
were found in the C-terminal end of the A-subunits. The aim of this study was to
investigate the role of the C-terminal end of the A-subunit in complex stability
and retrograde transport by generating truncated mutants where 2, 4, 6 and 8
amino acids were removed from the C-terminal end of Stx1A and Stx2A. The results
obtained show that removal of 6 or 8 amino acids from the Stx1A C-terminus
abolishes the AB5 complex integrity, while removing up to 8 amino acids from
Stx2A does not affect the complex in vivo (in the bacteria). We also present
results showing different levels of A1-subunit in HeLa cells after exposure to
Stx1, Stx2 and their truncated mutants.
PMID- 26443837
TI - Social Media Use Among Physicians and Trainees: Results of a National Medical
Oncology Physician Survey.
AB - PURPOSE: Cancer management requires coordinated care from many health care
providers, and its complexity requires physicians be up to date on current
research. Web-based social media support physician collaboration and information
sharing, but the extent to which physicians use social media for these purposes
remains unknown. The complex field of oncology will benefit from increased use of
online social media to enhance physician communication, education, and
mentorship. To facilitate this, patterns of social media use among oncologists
must be better understood. METHODS: A nine-item survey investigating physician
social media use, designed using online survey software, was distributed via e
mail to 680 oncology physicians and physicians in training in Canada. Responses
were analyzed using descriptive statistics. RESULTS: A total of 207 responses
(30%) were received; 72% of respondents reported using social media. Social media
use was highest, at 93%, in respondents age 25 to 34 years and lowest, at 39%, in
those age 45 to 54 years. This demonstrates a significant gap in social media use
between younger users and mid- to late-career users. The main barrier to use was
lack of free time. CONCLUSION: The identified gap in social media use between age
cohorts may have negative implications for communication in oncology. Despite
advancements in social media and efforts to integrate social media into medical
education, most oncologists and trainees use social media rarely, which, along
with the age-related gap in use, may have consequences for collaboration and
education in oncology. Investigations to further understand barriers to social
media use should be undertaken to enhance physician collaboration and knowledge
sharing through social media.
PMID- 26443838
TI - Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict
Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy:
American Society of Clinical Oncology Provisional Clinical Opinion Update 2015
Summary.
PMID- 26443839
TI - Reducing Oncology Unit Central Line-Associated Bloodstream Infections: Initial
Results of a Simulation-Based Educational Intervention.
AB - PURPOSE: Patients with cancer may be more vulnerable to infection because of
impaired immune competence as a result of their disease or chemotherapy-induced
neutropenia. In these patients, central line-associated bloodstream infections
(CLABSIs) can result in significant morbidity and mortality, prolonged
hospitalization, and increased costs. METHODS: We developed a staff educational
series to identify knowledge deficits and standardize the use, care, and
maintenance of central lines, with the goal of reducing the rate of CLABSIs. The
methodology used for this study employed a simulated central line care model,
focused on the re-education of nursing staff from January 2012 to June 2012, and
included a pretest, an educational blitz, and a post-test. The educational blitz
content was tailored to specifically address the significant practice and
knowledge deficits identified from the results of the pretest. RESULTS: On
completion of the education program, the post-test demonstrated a 16.9% increase
in nursing staff competence related to the care and maintenance of central lines.
Six months before the educational series (June 2011 to January 2012), the CLABSI
rate was 5.86 per 1,000 patient line-days. Throughout the educational series
(February 2012 to May 2012), the CLABSI rate was 3.45. The data revealed a CLABSI
rate of 3.43 for the 6-month period after the educational series (June 2012 to
January 2013). CONCLUSION: A targeted educational intervention using a simulated
central line care model improved competence in central line care and resulted in
decreased CLABSI rates for inpatient oncology patients.
PMID- 26443840
TI - The Synthetic Triterpenoid RTA 405 (CDDO-EA) Halts Progression of Liver Fibrosis
and Reduces Hepatocellular Carcinoma Size Resulting in Increased Survival in an
Experimental Model of Chronic Liver Injury.
AB - Patients with cirrhosis have an increased risk of developing liver cancer and a
higher rate of mortality. Cirrhosis currently has no known cure, and patients may
benefit from new agents aimed at alleviating their complications and slowing down
the rate of disease progression. Therefore, the effects of the orally
bioavailable synthetic triterpenoid 2-cyano-3,12-dioxooleana- 1,9(11)-dien-28
oate-ethyl amide (CDDO-EA, RTA 405), which has potent antioxidative and
antiinflammatory properties, was evaluated in a chronic carbon tetrachloride
(CCl(4))-induced model of liver cirrhosis and hepatocellular carcinoma (HCC).
Mice were injected with CCl(4) (to induce fibrosis and cirrhosis) or placebo
biweekly for 12 weeks followed by CDDO-EA in the diet for 18 weeks with continued
biweekly injections of CCl(4). Chronic CCl(4) administration resulted in
cirrhosis, ascites, and HCC formation, associated with increased serum
transforming growth factor-beta1, hepatic hydroxyproline content, and increased
serum bilirubin. CDDO-EA, whose administration commenced after establishment of
liver fibrosis, decreased liver fibrosis progression, serum bilirubin, ascites,
and HCC formation and markedly increased overall survival. CDDO-EA also
attenuated -TNFalpha (tumor necrosis factor-alpha), alpha-SMA (alpha smooth
muscle actin), augmented -IL-10 levels, and improved histologic and serologic
markers of fibrosis. CONCLUSIONS: CDDO-EA mitigates the progression of liver
fibrosis induced by chronic CCl(4) administration, which is associated with the
induction of antifibrogenic genes and suppression of profibrogenic genes.
PMID- 26443841
TI - Environmentally Relevant Concentrations of Arsenite Induce Dose-Dependent
Differential Genotoxicity Through Poly(ADP-Ribose) Polymerase Inhibition and
Oxidative Stress in Mouse Thymus Cells.
AB - Inhibition of DNA repair and oxidative stress are 2 common mechanisms associated
with arsenic-induced genotoxicity. The purpose of this study was to examine
mechanisms of genotoxicity induced by environmentally relevant doses of arsenite
(As(+3)) in mouse thymus cells. An increase in DNA damage and a decrease in
poly(ADP-ribose) polymerase (PARP) activity were seen in vitro following exposure
to 50 nM As(+3) in primary mouse thymus cells and a murine thymus pre-T cell
line, D1. 3,4-Dihydro-5[4-(1-piperindinyl) butoxyl]-1(2H)-isoquinoline, a well
characterized PARP inhibitor, also produced DNA damage in D1 cells, confirming
the correlation between PARP inhibition and DNA damage increase. As(+3) at 500 nM
induced double strand breaks (DSBs) in DNA and oxidative stress at 4 h in D1
cells, which was reversed at 18 h. No apoptosis or decrease of viability was
observed in these exposures. 4-Hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, a
widely-used antioxidant, was utilized to confirm that oxidative stress is
partially responsible for the increase of strand breaks in 500 nM As(+3) exposure
at 4 h. Expression of As(+3) exporters, Mdr1 and Mrp1, were found to be induced
by 500 nM As(+3) in D1 cells, suggesting a possible mechanism for reversal of
oxidative stress and DSBs at the 18-h timepoint. Finally, we showed that DNA
damage and PARP inhibition by As(+3) were reversed by zinc (Zn(+2)) at
approximate equimolar doses. Collectively, these results demonstrate that As(+3)
at doses within the nanomolar range induce genotoxicity by inhibiting PARP, and
produces oxidative stress at higher concentrations, which can be reversed by a
Zn(+2) treatment.
PMID- 26443842
TI - Correlation of In Vivo Versus In Vitro Benchmark Doses (BMDs) Derived From
Micronucleus Test Data: A Proof of Concept Study.
AB - In this study, we explored the applicability of using in vitro micronucleus (MN)
data from human lymphoblastoid TK6 cells to derive in vivo genotoxicity potency
information. Nineteen chemicals covering a broad spectrum of genotoxic modes of
action were tested in an in vitro MN test using TK6 cells using the same study
protocol. Several of these chemicals were considered to need metabolic
activation, and these were administered in the presence of S9. The Benchmark dose
(BMD) approach was applied using the dose-response modeling program PROAST to
estimate the genotoxic potency from the in vitro data. The resulting in vitro
BMDs were compared with previously derived BMDs from in vivo MN and
carcinogenicity studies. A proportional correlation was observed between the BMDs
from the in vitro MN and the BMDs from the in vivo MN assays. Further, a clear
correlation was found between the BMDs from in vitro MN and the associated BMDs
for malignant tumors. Although these results are based on only 19 compounds, they
show that genotoxicity potencies estimated from in vitro tests may result in
useful information regarding in vivo genotoxic potency, as well as expected
cancer potency. Extension of the number of compounds and further investigation of
metabolic activation (S9) and of other toxicokinetic factors would be needed to
validate our initial conclusions. However, this initial work suggests that this
approach could be used for in vitro to in vivo extrapolations which would support
the reduction of animals used in research (3Rs: replacement, reduction, and
refinement).
PMID- 26443843
TI - N-(2-Aminoethyl) Ethanolamine-Induced Morphological, Biochemical, and Biophysical
Alterations in Vascular Matrix Associated With Dissecting Aortic Aneurysm.
AB - Dissecting aortic aneurysm (DAA) is an extended tear in the wall of the aorta
along the plane of the vascular media. Our previous studies indicated in a
developmental animal model, that DAA was related to pathological alteration in
collagen, especially collagen type III. Accordingly, in the present studies,
neonatal aortic vascular smooth muscle cells (VSMC) and timed pregnant Sprague
Dawley rat dams were treated with N-(2-aminoethyl) ethanolamine (AEEA), which, as
shown previously, causes DAA in offspring. Morphological changes in extracellular
matrix (ECM) produced by VSMC in vitro were detailed with scanning electron
microscopy (SEM), and biochemical changes in cells and ECM produced by VSMCs were
defined by Western blotting. Biophysical changes of the collagen extracted from
both the ECM produced by VSMC and extracted from fetal rat aortas were studied
with atomic force microscopy (AFM). ECM disruption and irregularities were
observed in VSMCs treated with AEEA by SEM. Western blotting showed that collagen
type I was much more extractable, accompanied by a decrease of the pellet size
after urea buffer extraction in the AEEA-treated VSMC when compared with the
control. AFM found that collagen samples extracted from the fetal rat aortas of
the AEEA-treated dam, and in the in vitro formed ECM prepared by
decellularization, became stiffer, or more brittle, indicating that the 3D
organization associated with elasticity was altered by AEEA exposure. Our results
show that AEEA causes significant morphological, biochemical, and biomechanical
alterations in the ECM. These in vitro and in vivo strategies are advantageous in
elucidating the underlying mechanisms of DAA.
PMID- 26443844
TI - Mitochondrial biogenesis and dynamics in the developing and diseased heart.
AB - The mitochondrion is a complex organelle that serves essential roles in energy
transduction, ATP production, and a myriad of cellular signaling events. A finely
tuned regulatory network orchestrates the biogenesis, maintenance, and turnover
of mitochondria. The high-capacity mitochondrial system in the heart is regulated
in a dynamic way to generate and consume enormous amounts of ATP in order to
support the constant pumping function in the context of changing energy demands.
This review describes the regulatory circuitry and downstream events involved in
mitochondrial biogenesis and its coordination with mitochondrial dynamics in
developing and diseased hearts.
PMID- 26443845
TI - Dynamic enhancer-gene body contacts during transcription elongation.
AB - Enhancers govern transcription through multiple mechanisms, including the
regulation of elongation by RNA polymerase II (RNAPII). We characterized the
dynamics of looped enhancer contacts during synchronous transcription elongation.
We found that many distal enhancers form stable contacts with their target
promoters during the entire interval of elongation. Notably, we detected
additional dynamic enhancer contacts throughout the gene bodies that track with
elongating RNAPII and the leading edge of RNA synthesis. These results support a
model in which the gene body changes its position relative to a stable enhancer
promoter complex, which has broad ramifications for enhancer function and
architectural models of transcriptional elongation.
PMID- 26443846
TI - The Y3** ncRNA promotes the 3' end processing of histone mRNAs.
AB - We demonstrate that the Y3/Y3** noncoding RNAs (ncRNAs) bind to the CPSF
(cleavage and polyadenylation specificity factor) and that Y3** associates with
the 3' untranslated region (UTR) of histone pre-mRNAs. The depletion of Y3**
impairs the 3' end processing of histone pre-mRNAs as well as the formation and
protein dynamics of histone locus bodies (HLBs), the site of histone mRNA
synthesis and processing. HLB morphology is also disturbed by knockdown of the
CPSF but not the U7-snRNP components. In conclusion, we propose that the Y3**
ncRNA promotes the 3' end processing of histone pre-mRNAs by enhancing the
recruitment of the CPSF to histone pre-mRNAs at HLBs.
PMID- 26443847
TI - Role of the small subunit processome in the maintenance of pluripotent stem
cells.
AB - RNA-binding proteins (RBPs) play integral roles in gene regulation, yet only a
small fraction of RBPs has been studied in the context of stem cells. Here we
applied an RNAi screen for RBPs in mouse embryonic stem cells (ESCs) and
identified 16 RBPs involved in pluripotency maintenance. Interestingly, six
identified RBPs, including Krr1 and Ddx47, are part of a complex called small
subunit processome (SSUP) that mediates 18S rRNA biogenesis. The SSUP components
are preferentially expressed in stem cells and enhance the global translational
rate, which is critical to sustain the protein levels of labile pluripotency
factors such as Nanog and Esrrb. Furthermore, the SSUP proteins are required for
efficient reprogramming of induced pluripotent stem cells. Our study uncovers the
role of the SSUP and the importance of translational control in stem cell fate
decision.
PMID- 26443848
TI - Proliferation of progeria cells is enhanced by lamina-associated polypeptide
2alpha (LAP2alpha) through expression of extracellular matrix proteins.
AB - Lamina-associated polypeptide 2alpha (LAP2alpha) localizes throughout the
nucleoplasm and interacts with the fraction of lamins A/C that is not associated
with the peripheral nuclear lamina. The LAP2alpha-lamin A/C complex negatively
affects cell proliferation. Lamins A/C are encoded by LMNA, a single heterozygous
mutation of which causes Hutchinson-Gilford progeria syndrome (HGPS). This
mutation generates the lamin A variant progerin, which we show here leads to loss
of LAP2alpha and nucleoplasmic lamins A/C, impaired proliferation, and down
regulation of extracellular matrix components. Surprisingly, contrary to wild
type cells, ectopic expression of LAP2alpha in cells expressing progerin restores
proliferation and extracellular matrix expression but not the levels of
nucleoplasmic lamins A/C. We conclude that, in addition to its cell cycle
inhibiting function with lamins A/C, LAP2alpha can also regulate extracellular
matrix components independently of lamins A/C, which may help explain the
proliferation-promoting function of LAP2alpha in cells expressing progerin.
PMID- 26443849
TI - Widespread JNK-dependent alternative splicing induces a positive feedback loop
through CELF2-mediated regulation of MKK7 during T-cell activation.
AB - Alternative splicing is prevalent among genes encoding signaling molecules;
however, the functional consequence of differential isoform expression remains
largely unknown. Here we demonstrate that, in response to T-cell activation, the
Jun kinase (JNK) kinase MAP kinase kinase 7 (MKK7) is alternatively spliced to
favor an isoform that lacks exon 2. This isoform restores a JNK-docking site
within MKK7 that is disrupted in the larger isoform. Consistently, we show that
skipping of MKK7 exon 2 enhances JNK pathway activity, as indicated by c-Jun
phosphorylation and up-regulation of TNF-alpha. Moreover, this splicing event is
itself dependent on JNK signaling. Thus, MKK7 alternative splicing represents a
positive feedback loop through which JNK promotes its own signaling. We further
show that repression of MKK7 exon 2 is dependent on the presence of flanking
sequences and the JNK-induced expression of the RNA-binding protein CELF2, which
binds to these regulatory elements. Finally, we found that ~25% of T-cell
receptor-mediated alternative splicing events are dependent on JNK signaling.
Strikingly, these JNK-dependent events are also significantly enriched for
responsiveness to CELF2. Together, our data demonstrate a widespread role for the
JNK-CELF2 axis in controlling splicing during T-cell activation, including a
specific role in propagating JNK signaling.
PMID- 26443850
TI - Local regulation of the Srs2 helicase by the SUMO-like domain protein Esc2
promotes recombination at sites of stalled replication.
AB - Accurate completion of replication relies on the ability of cells to activate
error-free recombination-mediated DNA damage bypass at sites of perturbed
replication. However, as anti-recombinase activities are also recruited to
replication forks, how recombination-mediated damage bypass is enabled at
replication stress sites remained puzzling. Here we uncovered that the conserved
SUMO-like domain-containing Saccharomyces cerevisiae protein Esc2 facilitates
recombination-mediated DNA damage tolerance by allowing optimal recruitment of
the Rad51 recombinase specifically at sites of perturbed replication.
Mechanistically, Esc2 binds stalled replication forks and counteracts the anti
recombinase Srs2 helicase via a two-faceted mechanism involving chromatin
recruitment and turnover of Srs2. Importantly, point mutations in the SUMO-like
domains of Esc2 that reduce its interaction with Srs2 cause suboptimal levels of
Rad51 recruitment at damaged replication forks. In conclusion, our results reveal
how recombination-mediated DNA damage tolerance is locally enabled at sites of
replication stress and globally prevented at undamaged replicating chromosomes.
PMID- 26443851
TI - Genotoxicity of flubendazole and its metabolites in vitro and the impact of a new
formulation on in vivo aneugenicity.
AB - The anti-parasitic benzimidazole flubendazole has been used for many years to
treat intestinal infections in humans and animals. Previous genotoxicity studies
have shown that the compound is not a bacterial mutagen and a bone marrow
micronucleus test, using a formulation that limited systemic absorption, was
negative. The purpose of this study is to explore the genotoxicity of
flubendazole and its main metabolites in in vitro micronucleus studies and to
test a new oral formulation that improves systemic absorption in an in vivo
micronucleus test. The isolated metabolites were also screened using the Ames
test for bacterial mutagenicity. It was found that flubendazole, like other
chemically related benzimidazoles used in anti-parasitic therapies, is a potent
aneugen in vitro The hydrolysed metabolite of flubendazole is negative in these
tests, but the reduced metabolite (R- and S-forms) shows both aneugenic and
clastogenic activity. However, in vitro micronucleus tests of flubendazole in the
presence of rat liver S9 gave almost identical signals for aneugenicity as they
did in the absence of S9, suggesting that any clastogenicity from the reduced
metabolite is not sufficient to change the overall profile. Like flubendazole
itself, both metabolites are negative in the Ames test. Analysis of dose-response
curves from the in vitro tests, using recently developed point of departure
approaches, demonstrate that the aneugenic potency of flubendazole is very
similar to related anti-parasitic benzimidazoles, including albendazole, which is
used in mass drug administration programmes to combat endemic filarial diseases.
The in vivo micronucleus test of the new formulation of flubendazole also showed
evidence of induced aneugenicity. Analysis of the in vivo data allowed a
reference dose for aneugenicity to be established which can be compared with
therapeutic exposures of flubendazole when this has been established. Analysis of
the plasma from the animals used in the in vivo micronucleus test showed that
there is increased exposure to flubendazole compared with previously tested
formulations, as well as significant formation of the non-genotoxic hydrolysed
metabolite of flubendazole and small levels of the reduced metabolite. In
conclusion, this study shows that flubendazole is a potent aneugen in vitro with
similar potency to chemically related benzimidazoles currently used as anti
parasitic therapies. The reduced metabolite also has aneugenic properties as well
as clastogenic properties. Treatment with a new formulation of flubendazole that
allows increased systemic exposure, compared with previously used formulations,
also results in detectable aneugenicity in vivo. Based on the lack of
carcinogenicity of this class of benzimidazoles and the intended short-term
dosing, it is unlikely that flubendazole treatment will pose a carcinogenic risk
to patients.
PMID- 26443853
TI - News Feature: Reionizing the universe.
PMID- 26443852
TI - The genome as a record of environmental exposure.
AB - Whole genome sequencing of human tumours has revealed distinct patterns of
mutation that hint at the causative origins of cancer. Experimental
investigations of the mutations and mutation spectra induced by environmental
mutagens have traditionally focused on single genes. With the advent of faster
cheaper sequencing platforms, it is now possible to assess mutation spectra in
experimental models across the whole genome. As a proof of principle, we have
examined the whole genome mutation profiles of mouse embryo fibroblasts
immortalised following exposure to benzo[a]pyrene (BaP), ultraviolet light (UV)
and aristolochic acid (AA). The results reveal that each mutagen induces a
characteristic mutation signature: predominantly G->T mutations for BaP, C->T and
CC->TT for UV and A->T for AA. The data are not only consistent with existing
knowledge but also provide additional information at higher levels of genomic
organisation. The approach holds promise for identifying agents responsible for
mutations in human tumours and for shedding light on the aetiology of human
cancer.
PMID- 26443854
TI - Core Concept: Atom interferometry.
PMID- 26443856
TI - Drosophila TRPA1 isoforms detect UV light via photochemical production of H2O2.
AB - The transient receptor potential A1 (TRPA1) channel is an evolutionarily
conserved detector of temperature and irritant chemicals. Here, we show that two
specific isoforms of TRPA1 in Drosophila are H2O2 sensitive and that they can
detect strong UV light via sensing light-induced production of H2O2. We found
that ectopic expression of these H2O2-sensitive Drosophila TRPA1 (dTRPA1)
isoforms conferred UV sensitivity to light-insensitive HEK293 cells and
Drosophila neurons, whereas expressing the H2O2-insensitive isoform did not.
Curiously, when expressed in one specific group of motor neurons in adult flies,
the H2O2-sensitive dTRPA1 isoforms were as competent as the blue light-gated
channelrhodopsin-2 in triggering motor output in response to light. We found that
the corpus cardiacum (CC) cells, a group of neuroendocrine cells that produce the
adipokinetic hormone (AKH) in the larval ring gland endogenously express these
H2O2-sensitive dTRPA1 isoforms and that they are UV sensitive. Sensitivity of CC
cells required dTRPA1 and H2O2 production but not conventional phototransduction
molecules. Our results suggest that specific isoforms of dTRPA1 can sense UV
light via photochemical production of H2O2. We speculate that UV sensitivity
conferred by these isoforms in CC cells may allow young larvae to activate stress
response--a function of CC cells--when they encounter strong UV, an aversive
stimulus for young larvae.
PMID- 26443857
TI - An invertebrate smooth muscle with striated muscle myosin filaments.
AB - Muscle tissues are classically divided into two major types, depending on the
presence or absence of striations. In striated muscles, the actin filaments are
anchored at Z-lines and the myosin and actin filaments are in register, whereas
in smooth muscles, the actin filaments are attached to dense bodies and the
myosin and actin filaments are out of register. The structure of the filaments in
smooth muscles is also different from that in striated muscles. Here we have
studied the structure of myosin filaments from the smooth muscles of the human
parasite Schistosoma mansoni. We find, surprisingly, that they are
indistinguishable from those in an arthropod striated muscle. This structural
similarity is supported by sequence comparison between the schistosome myosin II
heavy chain and known striated muscle myosins. In contrast, the actin filaments
of schistosomes are similar to those of smooth muscles, lacking troponin
dependent regulation. We conclude that schistosome muscles are hybrids,
containing striated muscle-like myosin filaments and smooth muscle-like actin
filaments in a smooth muscle architecture. This surprising finding has broad
significance for understanding how muscles are built and how they evolved, and
challenges the paradigm that smooth and striated muscles always have distinctly
different components.
PMID- 26443858
TI - Selective optogenetic activation of arcuate kisspeptin neurons generates
pulsatile luteinizing hormone secretion.
AB - Normal reproductive functioning in mammals depends upon gonadotropin-releasing
hormone (GnRH) neurons generating a pulsatile pattern of gonadotropin secretion.
The neural mechanism underlying the episodic release of GnRH is not known,
although recent studies have suggested that the kisspeptin neurons located in the
arcuate nucleus (ARN) may be involved. In the present experiments we expressed
channelrhodopsin (ChR2) in the ARN kisspeptin population to test directly whether
synchronous activation of these neurons would generate pulsatile luteinizing
hormone (LH) secretion in vivo. Characterization studies showed that this
strategy targeted ChR2 to 70% of all ARN kisspeptin neurons and that, in vitro,
these neurons were activated by 473-nm blue light with high fidelity up to 30 Hz.
In vivo, the optogenetic activation of ARN kisspeptin neurons at 10 and 20 Hz
evoked high amplitude, pulse-like increments in LH secretion in anesthetized male
mice. Stimulation at 10 Hz for 2 min was sufficient to generate repetitive LH
pulses. In diestrous female mice, only 20-Hz activation generated significant
increments in LH secretion. In ovariectomized mice, 5-, 10-, and 20-Hz activation
of ARN kisspeptin neurons were all found to evoke LH pulses. Part of the sex
difference, but not the gonadal steroid dependence, resulted from differential
pituitary sensitivity to GnRH. Experiments in kisspeptin receptor-null mice,
showed that kisspeptin was the critical neuropeptide underlying the ability of
ARN kisspeptin neurons to generate LH pulses. Together these data demonstrate
that synchronized activation of the ARN kisspeptin neuronal population generates
pulses of LH.
PMID- 26443859
TI - A complexity classification of spin systems with an external field.
AB - We study the computational complexity of approximating the partition function of
a q-state spin system with an external field. There are just three possible
levels of computational difficulty, depending on the interaction strengths
between adjacent spins: (i) efficiently exactly computable, (ii) equivalent to
the ferromagnetic Ising model, and (iii) equivalent to the antiferromagnetic
Ising model. Thus, every nontrivial q-state spin system, irrespective of the
number q of spins, is computationally equivalent to one of two fundamental two
state spin systems.
PMID- 26443860
TI - Resting state of the human proton channel dimer in a lipid bilayer.
AB - The voltage-gated proton channel Hv1 plays a critical role in the fast proton
translocation that underlies a wide range of physiological functions, including
the phagocytic respiratory burst, sperm motility, apoptosis, and metastatic
cancer. Both voltage activation and proton conduction are carried out by a
voltage-sensing domain (VSD) with strong similarity to canonical VSDs in voltage
dependent cation channels and enzymes. We set out to determine the structural
properties of membrane-reconstituted human proton channel (hHv1) in its resting
conformation using electron paramagnetic resonance spectroscopy together with
biochemical and computational methods. We evaluated existing structural templates
and generated a spectroscopically constrained model of the hHv1 dimer based on
the Ci-VSD structure at resting state. Mapped accessibility data revealed deep
water penetration through hHv1, suggesting a highly focused electric field,
comprising two turns of helix along the fourth transmembrane segment. This region
likely contains the H(+) selectivity filter and the conduction pore. Our 3D model
offers plausible explanations for existing electrophysiological and biochemical
data, offering an explicit mechanism for voltage activation based on a one-click
sliding helix conformational rearrangement.
PMID- 26443861
TI - Calcineurin mediates homeostatic synaptic plasticity by regulating retinoic acid
synthesis.
AB - Homeostatic synaptic plasticity is a form of non-Hebbian plasticity that
maintains stability of the network and fidelity for information processing in
response to prolonged perturbation of network and synaptic activity. Prolonged
blockade of synaptic activity decreases resting Ca(2+) levels in neurons, thereby
inducing retinoic acid (RA) synthesis and RA-dependent homeostatic synaptic
plasticity; however, the signal transduction pathway that links reduced Ca(2+)
levels to RA synthesis remains unknown. Here we identify the Ca(2+)-dependent
protein phosphatase calcineurin (CaN) as a key regulator for RA synthesis and
homeostatic synaptic plasticity. Prolonged inhibition of CaN activity promotes RA
synthesis in neurons, and leads to increased excitatory and decreased inhibitory
synaptic transmission. These effects of CaN inhibitors on synaptic transmission
are blocked by pharmacological inhibitors of RA synthesis or acute genetic
deletion of the RA receptor RARalpha. Thus, CaN, acting upstream of RA, plays a
critical role in gating RA signaling pathway in response to synaptic activity.
Moreover, activity blockade-induced homeostatic synaptic plasticity is absent in
CaN knockout neurons, demonstrating the essential role of CaN in RA-dependent
homeostatic synaptic plasticity. Interestingly, in GluA1 S831A and S845A knockin
mice, CaN inhibitor- and RA-induced regulation of synaptic transmission is
intact, suggesting that phosphorylation of GluA1 C-terminal serine residues S831
and S845 is not required for CaN inhibitor- or RA-induced homeostatic synaptic
plasticity. Thus, our study uncovers an unforeseen role of CaN in postsynaptic
signaling, and defines CaN as the Ca(2+)-sensing signaling molecule that mediates
RA-dependent homeostatic synaptic plasticity.
PMID- 26443862
TI - A novel peroxisome proliferator response element modulates hepatic low-density
lipoprotein receptor gene transcription in response to PPARdelta activation.
AB - The hepatic expression of low-density lipoprotein (LDL) receptor (LDLR) gene is
regulated primarily at the transcriptional level by a sterol-regulatory element
(SRE) in its proximal promoter region which is the site of action of SRE-binding
protein 2 (SREBP2). However whether additional cis-regulatory elements contribute
to LDLR transcription has not been fully explored. We investigated the function
of a putative peroxisome proliferator-activated receptor (PPAR)-response element
(PPRE) sequence motif located at -768 to -752 bases upstream of the transcription
start site of human LDLR gene in response to PPARdelta activation. Promoter
luciferase reporter analyses showed that treating HepG2 cells with PPARdelta
agonist L165041 markedly increased the activity of a full-length LDLR promoter
construct (pLDLR-1192) without any effects on the shorter promoter reporter pLDLR
234 that contains only the core regulatory elements SRE-1 and SP1 sites.
Importantly, mutation of the PPRE sequence greatly attenuated the induction of
the full-length LDLR promoter activity by L165041 without affecting rosuvastatin
(RSV)-mediated transactivation. EMSA and ChIP assay further confirmed the binding
of PPARdelta to the LDLR-PPRE site. Treating HepG2 cells with L165041 elevated
the mRNA and protein expressions of LDLR without affecting the LDLR mRNA decay
rate. The induction of LDLR expression by PPARdelta agonist was further observed
in liver tissue of mice and hamsters treated with L165041. Altogether, our
studies identify a novel PPRE-mediated regulatory mechanism for LDLR
transcription and suggest that combined treatment of statin with PPARdelta
agonists may have advantageous effects on LDLR expression.
PMID- 26443863
TI - VID22 is required for transcriptional activation of the PSD2 gene in the yeast
Saccharomyces cerevisiae.
AB - Phosphatidylethanolamine (PE) in the yeast Saccharomyces cerevisiae is
synthesized through decarboxylation of phosphatidylserine (PS), catalysed by PS
decarboxylase 1 (Psd1p) and 2 (Psd2p) and the cytidine 5'-diphosphate (CDP)
ethanolamine (CDP-Etn) pathway. PSD1 null (psd1Delta) and PSD2 null (psd2Delta)
mutants are viable in a synthetic minimal medium, but a psd1Delta psd2Delta
double mutant exhibits Etn auxotrophy, which is incorporated into PE through the
CDP-Etn pathway. We have previously shown that psd1Delta is synthetic lethal with
deletion of VID22 (vid22Delta) [Kuroda et al. (2011) Mol. Microbiol. 80: , 248
265]. In the present study, we found that vid22Delta mutant exhibits Etn
auxotrophy under PSD1-depressed conditions. Deletion of VID22 in wild-type and
PSD1-depressed cells caused partial defects in PE formation through
decarboxylation of PS. The enzyme activity of PS decarboxylase in an extract of
vid22Delta cells was ~70% of that in wild-type cells and similar to that in
psd2Delta cells and the PS decarboxylase activity remaining in the PSD1-depressed
cells became almost negligible with deletion of VID22. Thus, the vid22Delta
mutation was suggested to cause a defect in the Psd2p activity. Furthermore,
vid22Delta cells were shown to be defective in expression of the PSD2 gene tagged
with 6*HA, the defect being ameliorated by replacement of the native promoter of
the PSD2 gene with a CYC1 promoter. In addition, an alpha-galactosidase reporter
assay revealed that the activity of the promoter of the PSD2 gene in vid22Delta
cells was ~5% of that in wild-type cells. These results showed that VID22 is
required for transcriptional activation of the PSD2 gene.
PMID- 26443864
TI - Nuclear protein kinase CLK1 uses a non-traditional docking mechanism to select
physiological substrates.
AB - Phosphorylation-dependent cell communication requires enzymes that specifically
recognize key proteins in a sea of similar, competing substrates. The protein
kinases achieve this goal by utilizing docking grooves in the kinase domain or
heterologous protein adaptors to reduce 'off pathway' targeting. We now provide
evidence that the nuclear protein kinase CLK1 (cell division cycle2-like kinase
1) important for splicing regulation departs from these classic paradigms by
using a novel self-association mechanism. The disordered N-terminus of CLK1
induces oligomerization, a necessary event for targeting its physiological
substrates the SR protein (splicing factor containing a C-terminal RS domain)
family of splicing factors. Increasing the CLK1 concentration enhances
phosphorylation of the splicing regulator SRSF1 (SR protein splicing factor 1)
compared with the general substrate myelin basic protein (MBP). In contrast,
removal of the N-terminus or dilution of CLK1 induces monomer formation and
reverses this specificity. CLK1 self-association also occurs in the nucleus, is
induced by the N-terminus and is important for localization of the kinase in sub
nuclear compartments known as speckles. These findings present a new picture of
substrate recognition for a protein kinase in which an intrinsically disordered
domain is used to capture physiological targets with similar disordered domains
in a large oligomeric complex while discriminating against non-physiological
targets.
PMID- 26443865
TI - Phosphoregulation of the C. elegans cadherin-catenin complex.
AB - Adherens junctions play key roles in mediating cell-cell contacts during tissue
development. In Caenorhabditis elegans embryos, the cadherin-catenin complex
(CCC), composed of the classical cadherin HMR-1 and members of three catenin
families, HMP-1, HMP-2 and JAC-1, is necessary for normal blastomere adhesion,
gastrulation, ventral enclosure of the epidermis and embryo elongation.
Disruption of CCC assembly or function results in embryonic lethality. Previous
work suggests that components of the CCC are subject to phosphorylation. However,
the identity of phosphorylated residues in CCC components and their contributions
to CCC stability and function in a living organism remain speculative. Using mass
spectrometry, we systematically identify phosphorylated residues in the essential
CCC subunits HMR-1, HMP-1 and HMP-2 in vivo. We demonstrate that HMR-1/cadherin
phosphorylation occurs on three sites within its beta-catenin binding domain that
each contributes to CCC assembly on lipid bilayers. In contrast, phosphorylation
of HMP-2/beta-catenin inhibits its association with HMR-1/cadherin in vitro,
suggesting a role in CCC disassembly. Although HMP-1/alpha-catenin is also
phosphorylated in vivo, phosphomimetic mutations do not affect its ability to
associate with other CCC components or interact with actin in vitro.
Collectively, our findings support a model in which distinct phosphorylation
events contribute to rapid CCC assembly and disassembly, both of which are
essential for morphogenetic rearrangements during development.
PMID- 26443867
TI - Response to the Letter to the Editor.
PMID- 26443866
TI - Improvement of skin wound healing in diabetic mice by kinin B2 receptor blockade.
AB - Impaired skin wound healing is a major medical problem in diabetic subjects.
Kinins exert a number of vascular and other actions limiting organ damage in
ischaemia or diabetes, but their role in skin injury is unknown. We investigated,
through pharmacological manipulation of bradykinin B1 and B2 receptors (B1R and
B2R respectively), the role of kinins in wound healing in non-diabetic and
diabetic mice. Using two mouse models of diabetes (streptozotocin-induced and
db/db mice) and non-diabetic mice, we assessed the effect of kinin receptor
activation or inhibition by subtype-selective pharmacological agonists (B1R and
B2R) and antagonist (B2R) on healing of experimental skin wounds. We also studied
effects of agonists and antagonist on keratinocytes and fibroblasts in vitro.
Levels of Bdkrb1 (encoding B1R) and Bdkrb2 (encoding B2R) mRNAs increased 1-2
fold in healthy and wounded diabetic skin compared with in non-diabetic skin.
Diabetes delayed wound healing. The B1R agonist had no effect on wound healing.
In contrast, the B2R agonist impaired wound repair in both non-diabetic and
diabetic mice, inducing skin disorganization and epidermis thickening. In vitro,
B2R activation unbalanced fibroblast/keratinocyte proliferation and increased
keratinocyte migration. These effects were abolished by co-administration of B2R
antagonist. Interestingly, in the two mouse models of diabetes, the B2R
antagonist administered alone normalized wound healing. This effect was
associated with the induction of Ccl2 (encoding monocyte chemoattractant protein
1)/Tnf (encoding tumour necrosis factor alpha) mRNAs. Thus stimulation of kinin
B2 receptor impairs skin wound healing in mice. B2R activation occurs in the
diabetic skin and delays wound healing. B2R blockade improves skin wound healing
in diabetic mice and is a potential therapeutic approach to diabetic ulcers.
PMID- 26443868
TI - More iconoclasts than icons?
PMID- 26443869
TI - Genetics: Fluent in DNA.
PMID- 26443871
TI - The Prevalence of Individual Histopathologic Features Varies according to
Autoantibody Status in Muscle Biopsies from Patients with Dermatomyositis.
AB - OBJECTIVE: Individual dermatomyositis (DM)-associated autoantibodies are
associated with distinct clinical phenotypes. This study was undertaken to
explore the association of these autoantibodies with specific muscle biopsy
features. METHODS: DM subjects with a muscle biopsy reviewed at Johns Hopkins had
sera screened for autoantibodies recognizing Mi-2, transcriptional intermediary
factor 1-gamma (TIF1-gamma), NXP2, MDA5, Ro52, PM-Scl, and Jo1. We also included
anti-Jo1-positive patients with polymyositis (PM) who had a biopsy read at Johns
Hopkins. Analyzed histological features included perifascicular atrophy,
perivascular inflammation, mitochondrial dysfunction, primary inflammation, and
myofiber necrosis. Duration of disease, biopsy location, and treatment at biopsy
were also analyzed. RESULTS: We studied 91 DM and 7 anti-Jo1-positive patients
with PM. In univariate analyses, TIF1-gamma+ patients had more mitochondrial
dysfunction (47% vs 18%; p = 0.05), NXP2+ patients had less primary inflammation
(0% vs 28%; p = 0.01), Mi-2+ patients had more primary inflammation (50% vs 19%;
p = 0.03), and PM-Scl+ patients had more primary inflammation (67% vs 18%; p =
0.004) than those who were negative for each autoantibody. Although reliability
was limited because of small sample numbers, multivariate analysis confirmed that
TIF1-gamma+ patients had more mitochondrial dysfunction [prevalence ratio (PR)
2.6, 95% CI 1.0-6.5, p = 0.05] and PM-Scl+ patients had more primary inflammation
(PR 5.2, 95% CI 2.0-13.4; p = 0.001) independent of disease duration at biopsy,
biopsy site, and treatment at biopsy. No differences in muscle biopsy features
were noted between anti-Jo1-positive patients diagnosed with DM and PM.
CONCLUSION: The prevalence of different histological features varies according to
autoantibody status in DM. Muscle biopsy features are similar in anti-Jo1
patients with and without a rash.
PMID- 26443872
TI - Systems Biology of Alzheimer's Disease. Preface.
PMID- 26443873
TI - Synergistic inhibition of PARP-1 and NF-kappaB signaling downregulates immune
response against recombinant AAV2 vectors during hepatic gene therapy.
AB - Host immune response remains a key obstacle to widespread application of adeno
associated virus (AAV) based gene therapy. Thus, targeted inhibition of the
signaling pathways that trigger such immune responses will be beneficial.
Previous studies have reported that DNA damage response proteins such as poly(ADP
ribose) polymerase-1 (PARP-1) negatively affect the integration of AAV in the
host genome. However, the role of PARP-1 in regulating AAV transduction and the
immune response against these vectors has not been elucidated. In this study, we
demonstrate that repression of PARP-1 improves the transduction of single
stranded AAV vectors both in vitro (~174%) and in vivo (two- to 3.4-fold).
Inhibition of PARP-1, also significantly downregulated the expression of several
proinflammatory and cytokine markers such as TLRs, ILs, NF-kappaB subunit
proteins associated with the host innate response against self-complementary AAV2
vectors. The suppression of the inflammatory response targeted against these
vectors was more effective upon combined inhibition of PARP-1 and NF-kappaB
signaling. This strategy also effectively attenuated the AAV capsid-specific
cytotoxic T-cell response, with minimal effect on vector transduction, as
demonstrated in normal C57BL/6 and hemophilia B mice. These data suggest that
targeting specific host cellular proteins could be useful to attenuate the immune
barriers to AAV-mediated gene therapy.
PMID- 26443874
TI - Radiology on Board the PLA(N) Peace Ark Hospital Ship During a Humanitarian
Medical Relief Mission to the Philippines.
AB - OBJECTIVE: From November 24 to December 10, 2013, the Chinese People's Liberation
Army Navy [PLA(N)] hospital ship Peace Ark was deployed to the Leyte Gulf in the
Philippines to provide humanitarian medical relief in Tacloban after Typhoon
Haiyan. The purpose of this study was to assess the radiological services aboard
the ship to provide guidance for future missions. METHODS: A retrospective review
was performed on a cohort of 109 patients who underwent digital radiography (DR)
and 59 patients who underwent computed tomography (CT) scans during a 16-day
period during a humanitarian medical relief mission to the Philippines. Patient
demographics, DR findings, and CT findings were analyzed. RESULTS: The mean age
of the 109 DR patients was 39.7 years for the 64 males and 43.7 years for the 45
females. A total of 148 DR examinations were performed of the chest (n=109),
extremities (n=35), and spine (n=4). The mean age of the 59 CT patients was 43.8
years for the 32 males and 49.1 years for the 27 females. A total of 72 CT scans
were performed of the head and neck (n=36), thorax (n=24), abdomen (n=5), spine
(n=4), and extremities (n=3). The imaging findings mainly included disaster
related and non-disaster-related fractures, pulmonary tuberculosis, pulmonary
infection, acute brain infarction, intracranial hematoma, and occupying lesions.
CONCLUSION: Analysis of radiological services during a humanitarian medical
relief mission to the Philippines provided meaningful information for future
humanitarian medical relief missions.
PMID- 26443875
TI - GRIN1 polymorphisms do not affect susceptibility or phenotype in NMDA receptor
encephalitis.
AB - OBJECTIVE: To determine whether distinct single nucleotide polymorphisms (SNPs)
within the glutamate receptor ionotropic NMDA 1 gene (GRIN1) are associated with
NMDA receptor (NMDAR) encephalitis and whether these same variants are associated
with variability in the clinical presentation and course of affected patients.
METHODS: We performed clinical follow-up on 48 patients with NMDAR encephalitis
and NMDAR autoantibodies detected in serum or CSF. All RefSeq GRIN1 coding exons
were sequenced in 39 Caucasian-European patients, and the frequencies of SNPs
were compared with those of an ethnically similar population using a case-control
study design. Predetermined clinical variables were compared between patients
with and without identified SNPs. RESULTS: Two SNPs were identified in GRIN1: 24
(62%) Caucasian-European patients with NMDAR encephalitis had alternate alleles
at both rs6293 (exon 6) and rs1126442 (exon 7; exon numbering according to
NM_001185090). The SNPs were in complete linkage disequilibrium. The frequency of
these variants did not differ between patients with NMDAR encephalitis and
ethnically matched individuals in the general population. No differences in
clinical presentation, measures of disease severity, clinical course, or outcomes
were observed between patients with different genotypes at these SNPs.
CONCLUSION: Disease susceptibility or course in patients with NMDAR encephalitis
was not strongly affected by SNPs in GRIN1. This study provides an estimate of
the frequency of SNPs in GRIN1 in patients with NMDAR encephalitis and emphasizes
the need for multisite collaborative studies enrolling larger numbers of patients
to identify the genetic contributions to NMDAR encephalitis.
PMID- 26443876
TI - Grounding after moderate eccentric contractions reduces muscle damage.
AB - Grounding a human to the earth has resulted in changes in the physiology of the
body. A pilot study on grounding and eccentric contractions demonstrated
shortened duration of pain, reduced creatine kinase (CK), and differences in
blood parameters. This follow-up study was conducted to investigate the effects
of grounding after moderate eccentric contractions on pain, CK, and complete
blood counts. Thirty-two healthy young men were randomly divided into grounded
(n=16) and sham-grounded (n=16) groups. On days 1 through 4, visual analog scale
for pain evaluations and blood draws were accomplished. On day 1, the
participants performed eccentric contractions of 200 half-knee bends. They were
then grounded or sham-grounded to the earth for 4 hours on days 1 and 2. Both
groups experienced pain on all posttest days. On day 2, the sham-grounded group
experienced significant CK increase (P<0.01) while the CK of the grounded group
did not increase significantly; the between-group difference was significant
(P=0.04). There was also an increase in the neutrophils of the grounded group on
day 3 (P=0.05) compared to the sham-grounded group. There was a significant
increase in platelets in the grounded group on days 2 through 4. Grounding
produced changes in CK and complete blood counts that were not shared by the sham
grounded group. Grounding significantly reduced the loss of CK from the injured
muscles indicating reduced muscle damage. These results warrant further study on
the effects of earthing on delayed onset muscle damage.
PMID- 26443877
TI - High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results.
AB - PURPOSE: High-dose-rate (HDR) brachytherapy was originally used with external
beam radiation therapy (EBRT) to increase the dose to the prostate without
injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy
is safe and effective. We adapted it for use without EBRT for cases not requiring
lymph node treatment. PATIENTS AND METHODS: We entered the patient demographics,
disease characteristics, and treatment parameters into a prospective registry and
serially added follow-up data for 448 men with low-risk (n=288) and intermediate
risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64
years (range 42-90). The median prostate-specific antigen (PSA) level was 6.0
ng/mL (range 0.2-18.2). The Gleason score was <=6 in 76% and 7 in 24%. The median
dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and
survival rates were calculated. Adverse events were graded according to the
Common Toxicity Criteria of Adverse Events. RESULTS: The median follow-up period
was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free
survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI
95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The
local control, distant metastasis-free survival, and cause-specific survival were
99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%
99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer
Network risk group, patient age, and androgen deprivation therapy did not
significantly correlate with disease control or survival. No late grade 3 to 4
rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in
4.9% (grade 3 in 4.7%). CONCLUSIONS: HDR monotherapy is a safe and highly
effective treatment of low- and intermediate-risk prostate cancer.
PMID- 26443878
TI - The influence of communication and information sources upon decision-making
around complementary and alternative medicine use for back pain among Australian
women aged 60-65 years.
AB - This study examined factors influencing decision-making on complementary and
alternative medicine (CAM) use for back pain and back pain sufferers'
communication about CAM use. A cross-sectional postal survey was conducted in
2011/2012 as a sub-study of the Australian Longitudinal Study on Women's Health
(ALSWH). The sample contained 1620 women from the 1945-1951 cohort of the ALSWH,
aged 60-65 years who were eligible for the sub-study, as they had experienced
back pain during 12 months prior to the survey. Of these, 1310 (80.9%) returned
completed questionnaires. A significant proportion of women consulted a CAM
practitioner (76%, n = 1001) and/or had self-prescribed CAM treatment (75%, n =
985). Of the women who used CAM for their back pain, 20% consulted their general
practitioner (GP) prior to using CAM and 34% always informed their GP following
CAM use. Forty-three per cent of the women were influenced by their doctors, 39%
by friends/colleagues, 36% by family/relatives, 33% by their partner, 30% by a
CAM practitioner, 20% by a pharmacist, 16% by a book/magazine, 11% by mass media,
10% by an allied health worker and 6% by the Internet. Our results show that
information sources used by women for their decision-making on CAM use differed
according to the symptoms. While non-professional information sources (e.g.
family/relatives) positively influenced women in their decision to use CAM for a
range of back pain-related symptoms (e.g. headaches/migraines), doctors and
allied health workers (e.g. nurses) negatively influenced women in their decision
to consult a CAM practitioner for a range of back pain-related symptoms (e.g.
headaches/migraines, neck pain). Women seek information from a wide range of
professional and non-professional sources with regard to their decision-making
around CAM use for back pain. Back pain care providers need to ensure effective
communication with their back pain patients regarding safe, effective and co
ordinated back pain care options.
PMID- 26443879
TI - Bleeding, Transfusion, and Mortality on Extracorporeal Life Support: ECLS Working
Group on Thrombosis and Hemostasis.
AB - BACKGROUND: Bleeding may occur frequently during adult extracorporeal life
support; however, there are no detailed investigations of bleeding events, red
blood cell transfusion, and their impact on mortality. The purpose of our study
was to characterize the incidence of bleeding and red blood cell transfusion
during adult extracorporeal life support and examine the impact on mortality.
METHODS: We performed a retrospective analysis of adult extracorporeal life
support patients over approximately a 3-year period. The incidence of bleeding
events and transfusions were recorded. Unadjusted and adjusted multivariate
logistic regression analyses were performed to estimate the odds of inhospital
mortality among patients with bleeding and for each red blood cell unit
transfused. Ninety-day survival was compared between patients who bled and those
who did not. RESULTS: Serious bleeding events occurred in 74 of 132 patients
(56.1%), and the rate of bleeding was 10 events per 100 days. The crude odds
ratio for inhospital mortality in patients who bled was 2.22 (95% confidence
interval [CI]: 1.00 to 4.94, p = 0.05); and for each unit of red blood cells
transfused, it was 1.03 (95% CI: 1.01 to 1.04, p = 0.005). The adjusted odds
ratios for bleeding and red blood cell transfusions were 0.90 (95% CI: 0.37 to
2.19, p = 0.82) and 1.03 (95% CI: 1.00 to 1.06, p = 0.04). There was a trend
toward decreased 90-day survival among patients who bled compared with patients
who did not (46.7% versus 64.9%, p = 0.08). CONCLUSIONS: Bleeding and red blood
cell transfusion occur frequently during adult extracorporeal life support, but
only the amount of red blood cell transfusion is associated with inhospital
mortality after controlling for confounding variables.
PMID- 26443880
TI - A European Multicenter Study of 616 Patients Receiving the Freedom Solo Stentless
Bioprosthesis.
AB - BACKGROUND: The purpose of this study was to evaluate the safety and performance
of the Freedom Solo valve in aortic valve replacement by clinical and hemodynamic
outcomes. METHODS: Six hundred sixteen patients underwent aortic valve
replacement in 18 European centers; mean age was 74.5 +/- 5.9 years, 54.1% of the
patients were male, and concomitant procedures were performed in 43.2% of the
patients. The majority (69%) of the implanted sizes were 23 mm and 25 mm.
RESULTS: At 1 year, overall survival was 94.0%, whereas freedom from valve
related death was 98.6%. There were 9 (1.5%) early (<= 30 days) and 27 (4.4%)
late (>30 days) deaths. Early and late valve-related mortality was 0.3% (n = 2)
and 1.1% (n = 7), respectively. Freedom from explant was 97.6%; 10 valves were
explanted for endocarditis and 4 for paravalvular leak. There were 10 (1.6%)
early and 5 (0.8%) late strokes. Atrioventricular block requiring pacemaker
implant occurred in 8 (1.3%) and 1 (0.2%) patients in the early and late
postoperative period, respectively. Thrombocytopenia was seen in 27 cases (4.4%)
in the early postoperative period. Preoperatively, 93.8% of patients were in New
York Heart Association functional classes II through IV, whereas at 1 year 96.9%
of patients were in New York Heart Association functional classes I and II. At 1
year follow-up, mean and peak pressure gradients were 7.2 and 14.6 mm Hg,
respectively. Indexed left ventricular mass decreased by 12% from 138 g/m(2) at
discharge to 122 g/m(2) at 1 year. CONCLUSIONS: At 1-year follow-up after Freedom
Solo implantation, we found acceptable clinical results with low mortality and
morbidity and good hemodynamic performance, confirming safety and effectiveness
in this multicenter experience.
PMID- 26443881
TI - Long-Term Effect of an Interdisciplinary Supportive Care Intervention for Lung
Cancer Survivors After Surgical Procedures.
AB - BACKGROUND: Surgical procedures provide the best chance for cure and long-term
survival in non-small cell cancer (NSCLC). Persistent symptoms after surgical
procedures are common, and they can negatively affect health-related quality of
life (HRQOL). The purpose of this study was to examine the long-term effect of an
interdisciplinary supportive care intervention to improve HRQOL, psychological
distress, and symptoms in lung cancer survivors who were treated surgically.
METHODS: Patients undergoing curative intent resection for NSCLC were enrolled in
a prospective sequential design whereby the control group was accrued first,
followed by the intervention group. Patients in the intervention group were
assessed and presented by nurses at weekly interdisciplinary care meetings before
surgical procedures, and received four educational sessions (physical,
psychological, social, and spiritual well-being) after surgical procedures.
Appropriate symptom management, social work, rehabilitation, and spiritual
support interventions were coordinated by the study nurse. In both groups, HRQOL,
psychological distress, and symptom severity were assessed at baseline and at 6,
12, 24, 36, and 52 weeks with the use of surveys that included the validated
Functional Assessment of Cancer Therapy-Lung (FACT-L), Lung Cancer Subscale
(LCS), and Distress Thermometer. Mean survey scores were analyzed with factorial
analysis of covariance at 12 months. RESULTS: A total of 71 survivors (control =
33; intervention = 38) were accrued. No difference was found in age, baseline
performance status, or stage of disease between groups. Patients in the
intervention group had significantly less distress (mean, 1.0 versus 4.0; range,
0 to 10; p < 0.001) and more favorable mean FACT-L scores (126.1 versus 98.7;
range, 0 to 140; p < 0.001) and LCS scores (29.4 versus 23.6; range, 0 to 32; p <
0.001) at 12 months. The mean scores of all categories of questions in FACT-L
(physical, social/family, emotional, and functional well-being) were considerably
more favorable in the intervention group at 12 months. CONCLUSIONS: An
interdisciplinary supportive care intervention improves psychological distress
and HRQOL at 12 months after lung cancer surgical procedures. This study has
important implications in improving HRQOL of lung cancer survivors after surgical
procedures. Further study is warranted on incorporating the interdisciplinary
personalized interventions used in this study into clinical practice for lung
cancer survivors.
PMID- 26443882
TI - Extra-articular step osteotomy of the olecranon: A biomechanical assessment.
AB - BACKGROUND: Trans-olecranon chevron osteotomies (COs) remain the gold standard
surgical approach to type C fractures of the distal humerus. This technique is
associated with a high complication rate and development of an extra-articular
olecranon osteotomy may be advantageous. The aim of this study was to compare the
load to failure of COs with extra-articular oblique osteotomies (OOs) as well as
modified, extra-articular step osteotomies (SOs). METHODS: These three
osteotomies and their subsequent fixation utilizing a standardized tension band
wiring technique were tested in 42 composite analog ulnae models at 20 degrees
and 70 degrees of flexion. Triceps loading was simulated with a servo hydraulic
testing machine. All specimens were isometrically loaded until failure. Kinematic
and force data, as well as interfragmentary motion were recorded. RESULTS: At 70
degrees , CO failed at a mean load of 963 N (SD 104 N), the OO at 1512 N (SD 208
N) and the SO at 1484 N (SD 153 N), (P<0.001). At 20 degrees , CO failed at a
mean load of 707 N (SD 104 N) and OO at 1009 N (SD 85 N) (P=0.006). The highest
load to failure was observed for the SO, which was 1277 N (SD 172 N). The load to
failure of the SO was significantly higher than the CO as well as the OO.
CONCLUSION: Extra-articular osteotomies showed a significantly higher load to
failure in comparison to traditional CO. At near full extension (20 degrees of
flexion), this biomechanical advantage was further enhanced by a step-cut
modification of the extra-articular oblique osteotomy.
PMID- 26443883
TI - California's Early Coverage Expansion under the Affordable Care Act: A County
Level Analysis.
AB - OBJECTIVE: To assess the coverage effects of California's 2011 Low-Income Health
Program (LIHP), enacted as an "early expansion" under the Affordable Care Act
(ACA), and to demonstrate the feasibility of using Census data to measure county
level coverage changes. DATA SOURCES/STUDY SETTING: 2008-2012 American Community
Survey (ACS). The sample contained California adults ages 19-64 years (n =
237,876) and children 0-18 years (n = 113,159) with incomes below 200 percent of
the federal poverty level. STUDY DESIGN: Differences-in-differences analysis
comparing public coverage, private insurance, and the uninsured rate in counties
that expanded the LIHP in 2011 versus California counties not expanding during
this time. Additional analyses tested for heterogeneous impacts of the LIHP and
spillover effects on children. PRINCIPAL FINDINGS: Compared to nonexpansion
counties, public coverage for adults increased by 1.8 percentage points (p = .02)
in expanding counties, while the uninsured rate declined by 2.1 percentage points
(p = .01). There was no significant change in private coverage. Public coverage
gains were largest for Latinos and those with limited English proficiency. The
expansion produced a positive spillover effect on children's Medicaid enrollment.
CONCLUSIONS: California's 2011 expansion produced significant increases in public
coverage for low-income individuals, particularly Latinos. Substate coverage
analyses with the ACS can add valuable detail to future assessments of the ACA.
PMID- 26443884
TI - Progression after spontaneous regression in lung large cell neuroendocrine
carcinoma: Report of a curative resection.
AB - We present the first reported case of lung large cell neuroendocrine carcinoma
(LCNEC) with spontaneous regression followed by progression. An 85-year-old woman
presented with a 2.8-cm nodule in the right upper lung lobe on chest computed
tomography. After four months, the tumor decreased to 1.8 cm and remained
unchanged in size for the next three months, but it grew to 8.6 cm and invaded
the mediastinal fat tissue after approximately one year. Ultrasound echo-guided
percutaneous biopsy revealed the tumor to be LCNEC. The patient underwent a right
upper lobectomy with lymph node dissection. She had a good postoperative course
with no complications. Physicians and surgeons should be aware that radiographic
regression of a pulmonary nodule does not necessarily exclude the possibility of
lung cancer.
PMID- 26443886
TI - Design of isolated iron species for Fenton reactions: lyophilization beats
calcination treatment.
AB - Lyophilization is used to prepare a Fenton catalyst containing a predominant
amount of isolated Fe(3+) species with an 8.90% iron content. This catalyst shows
a higher catalytic rate and H2O2 utilization efficiency but lower iron leaching
in phenol degradation, compared with the calcination sample.
PMID- 26443885
TI - Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons.
AB - Sensing force is crucial to maintain the viability of all living cells. Despite
its fundamental importance, how force is sensed at the molecular level remains
largely unknown. Here we show that stomatin-like protein-3 (STOML3) controls
membrane mechanics by binding cholesterol and thus facilitates force transfer and
tunes the sensitivity of mechano-gated channels, including Piezo channels. STOML3
is detected in cholesterol-rich lipid rafts. In mouse sensory neurons, depletion
of cholesterol and deficiency of STOML3 similarly and interdependently attenuate
mechanosensitivity while modulating membrane mechanics. In heterologous systems,
intact STOML3 is required to maintain membrane mechanics to sensitize Piezo1 and
Piezo2 channels. In C57BL/6N, but not STOML3(-/-) mice, tactile allodynia is
attenuated by cholesterol depletion, suggesting that membrane stiffening by
STOML3 is essential for mechanical sensitivity. Targeting the STOML3-cholesterol
association might offer an alternative strategy for control of chronic pain.
PMID- 26443887
TI - Editorial Comment for Wiener et al.
PMID- 26443888
TI - Comparison of carbon-sulfur and carbon-amine bond in therapeutic drug: 4beta-S
aromatic heterocyclic podophyllum derivatives display antitumor activity.
AB - Herein is a first effort to systematically study the significance of carbon
sulfur (C-S) and carbon-amine (C-NH) bonds on the antitumor proliferation
activity of podophyllum derivatives and their precise mechanism of apoptosis.
Compared with the derivative modified by a C-NH bond, the derivative modified by
a C-S bond exhibited superior antitumor activity, the inhibition activity of
target proteins tubulin or Topo II, cell cycle arrest, and apoptosis induction.
Antitumor mechanistic studies showed that the death receptor and the
mitochondrial apoptotic pathways were simultaneously activated by the C-S bond
modified aromatic heterocyclic podophyllum derivatives with a higher cellular
uptake percentage of 60-90% and induction of a higher level of reactive oxygen
species (ROS). Only the mitochondrial apoptotic pathway was activated by the C-NH
bond modified aromatic heterocyclic podophyllum derivatives, with a lower
cellular uptake percentage of 40-50%. This study provided insight into effects of
the C-S and C-NH bond modification on the improvement of the antitumor activity
of Podophyllum derivatives.
PMID- 26443890
TI - The EMG activity-acceleration relationship to quantify the optimal vibration load
when applying synchronous whole-body vibration.
AB - PURPOSE: To date are lacking methodological approaches to individualizing whole
body vibration (WBV) intensity. The aim of this study was: (1) to determine the
surface-electromyography-root-mean-square (sEMG(RMS))-acceleration load
relationship in the vastus lateralis (VL), vastus medialis (VM), rectus femoris
(RF), lateral gastrocnemius (LG) muscles during synchronous WBV, and (2) to
assess the reliability of the acceleration corresponding to the maximal
sEMG(RMS). METHODS: Twenty-five sportsman voluntarily took part in this study
with a single-group, repeated-measures design. All subjects postured themselves
in an isometric half-squat during nine trials in the following conditions: no
vibrations and random vibrations of different acceleration loads (from 0.12 to
5.72 g). RESULTS: The sEMG(RMS) were dependent on the acceleration loads in the
VL (p = 0.0001), LG (p = 0.0001) and VM (p = 0.011) muscles; while RF was not
affected by the acceleration loads (p = 0.508). The comparisons among the
sEMG(RMS)-accelerations relationships revealed a significant difference between
the LG and the others muscles (p = 0.001). No significant difference was found
between the different thigh muscles (p > 0.05). The intra-class correlation
coefficient ranged from 0.87 to 0.99 for the measurements performed on the LG, VL
and VM. CONCLUSIONS: The sEMG(RMS)-acceleration relationship in the VL, VM and LG
is a reliable test to individualize the WBV intervention.
PMID- 26443892
TI - Dehydrodipeptide Hydrogelators Containing Naproxen N-Capped Tryptophan: Self
Assembly, Hydrogel Characterization, and Evaluation as Potential Drug
Nanocarriers.
AB - In this work, we introduce dipeptides containing tryptophan N-capped with the
nonsteroidal anti-inflammatory drug naproxen and C-terminal dehydroamino acids,
dehydrophenylalanine (DeltaPhe), dehydroaminobutyric acid (DeltaAbu), and
dehydroalanine (DeltaAla) as efficacious protease resistant hydrogelators.
Optimized conditions for gel formation are reported. Transmission electron
microscopy experiments revealed that the hydrogels consist of networks of
micro/nanosized fibers formed by peptide self-assembly. Fluorescence and circular
dichroism spectroscopy indicate that the self-assembly process is driven by
stacking interactions of the aromatic groups. The naphthalene groups of the
naproxen moieties are highly organized in the fibers through chiral stacking.
Rheological experiments demonstrated that the most hydrophobic peptide
(containing C-terminal DeltaPhe) formed more elastic gels at lower critical
gelation concentrations. This gel revealed irreversible breakup, while the C
terminal DeltaAbu and DeltaAla gels, although less elastic, exhibited structural
recovery and partial healing of the elastic properties. A potential antitumor
thieno[3,2-b]pyridine derivative was incorporated (noncovalently) into the gel
formed by the hydrogelator containing C-terminal DeltaPhe residue. Fluorescence
and Forster resonance energy transfer measurements indicate that the drug is
located in a hydrophobic environment, near/associated with the peptide fibers,
establishing this type of hydrogel as a good drug-nanocarrier candidate.
PMID- 26443893
TI - Low prevalence of long-term breastfeeding among women with type 2 diabetes.
AB - OBJECTIVE: To investigate the prevalence of long-term breastfeeding among women
with type 2 diabetes compared to women with type 1 diabetes and to identify
predictors of long-term breastfeeding for women with pre-gestational diabetes.
METHODS: In total, 149 women with diabetes were interviewed about long-term
breastfeeding, defined as any breastfeeding 4 months postpartum. RESULTS: Ninety
eight percent of the women aimed to breastfeed. At time of discharge, any
breastfeeding was frequent for both groups of women (86% versus 93%, p = 0.17).
However, 4 months postpartum, the 44 women with type 2 diabetes showed
significantly lower prevalence of breastfeeding than the 105 women with type 1
diabetes (34% versus 61%, p < 0.01). Number of feedings in the first 24 h was an
independent positive predictor, whereas pre-pregnancy body mass index (BMI) and
smoking were independent negative predictors of long-term breastfeeding.
CONCLUSION: The prevalence of long-term breastfeeding among women with type 2
diabetes was considerably lower than in women with type 1 diabetes. Number of
feedings in the first 24 h was positive and BMI and smoking were negative
predictors of long-term breastfeeding in women with pre-gestational diabetes.
PMID- 26443891
TI - Changes in lower extremity peak angles, moments and muscle activations during
stair climbing at different speeds.
AB - Stair climbing is a common daily activity, yet there is no basic knowledge on how
lower extremity joint angles, moments or muscle activations are affected by stair
climbing speed. This information will determine whether speed matching is
necessary for stair climbing studies. Moreover, changes in lower extremity
biomechanics during stair climbing at different speeds will aid in the clinical
interpretation of a patient's maximal stair climbing speed. Thirty healthy
participants provided consent. Kinematics, kinetics, and muscle activations were
collected on a three step staircase. Subjects climbed the staircase at normal,
slow and fast self-selected speeds. Linear mixed models for repeated measures
were used to study the associations between speed and the lower extremity peak
joint angles and moments, and muscle activations. The peak hip flexion and
extension moments increased with increasing speed, while peak knee flexion moment
did not vary consistently with speed. The peak muscle activations varied
consistently with respect to the sagittal plane kinetics. These results suggest
that in healthy subjects, the hip is the greatest contributor when modulating
stair climbing speed, while additional knee contributions do not appear necessary
to increase speed. Further stair studies should consider speed matching in order
to accurately assess biomechanical differences.
PMID- 26443894
TI - Perceptual assessment of dysarthria: Comparison of a general and a detailed
assessment protocol.
AB - OBJECTIVE: The present, preliminary study was designed to investigate whether the
results of the use of a detailed assessment protocol ad modum the Mayo Clinic
rating of dysarthria and that of a more general assessment protocol,
corresponding to ratings of deviances of the different speech production
processes, differed primarily in terms of reliability. PATIENTS AND METHODS:
Recordings of text readings of 20 patients with various degrees and types of
dysarthria were assessed using both protocols by five clinicians with extensive
experience in assessment of neurogenic communication disorders, and results from
both assessments were compared. RESULTS: The general assessment protocol was
carried out with higher intra- and inter-rater reliability compared with the
detailed assessment protocol. Perceptual deviations were identified in the same
domains using both protocols, although only the more detailed protocol could be
used to specify particular audible symptoms. Monotony, imprecise consonants, and
harsh voice were the most prominent deviations identified with the detailed
protocol. CONCLUSION: It is concluded that a general assessment protocol is
sufficient to identify problem areas reliably and indicate severity of dysarthria
but needs to be complemented with a short description of the most prominent
audible symptoms and an assessment of intelligibility.
PMID- 26443889
TI - Peste des petits ruminants.
AB - Peste des petits ruminants virus causes a highly infectious disease of small
ruminants that is endemic across Africa, the Middle East and large regions of
Asia. The virus is considered to be a major obstacle to the development of
sustainable agriculture across the developing world and has recently been
targeted by the World Organisation for Animal Health (OIE) and the Food and
Agriculture Organisation (FAO) for eradication with the aim of global elimination
of the disease by 2030. Fundamentally, the vaccines required to successfully
achieve this goal are currently available, but the availability of novel vaccine
preparations to also fulfill the requisite for differentiation between infected
and vaccinated animals (DIVA) may reduce the time taken and the financial costs
of serological surveillance in the later stages of any eradication campaign.
Here, we overview what is currently known about the virus, with reference to its
origin, updated global circulation, molecular evolution, diagnostic tools and
vaccines currently available to combat the disease. Further, we comment on recent
developments in our knowledge of various recombinant vaccines and on the
potential for the development of novel multivalent vaccines for small ruminants.
PMID- 26443896
TI - ?
PMID- 26443895
TI - The effects of direction similarity in visual working memory: Behavioural and
event-related potential studies.
AB - Object similarity can improve visual working memory (VWM) performance in the
change-detection task, but impair the recognition performance when it occurs at
retrieval of VWM in the recognition task. The effect of direction similarity is
an issue that has not been well resolved. Furthermore, electrophysiological
evidence in support of the mechanisms that underlie the effects of similarity is
still scarce. In the current study, we conducted three behavioural experiments to
examine the effects of direction similarity on memory performance with regard to
both the encoding and retrieval phases of VWM and one event-related potential
(ERP) experiment to explore the neural signatures of direction similarity in VWM.
Our behavioural studies indicated that direction similarity improved performance
when it occurred at the encoding phase but impaired performance when it occurred
at the retrieval phase. Moreover, the ERP experiment showed that the amplitude of
the contralateral delay activity (CDA) increased with the increasing set size for
similar but not dissimilar directions. In addition, the CDA amplitude for similar
directions was lower than that for dissimilar directions at set size 2. Taken
together, these findings suggest that direction similarity at encoding has a
positive effect on VWM performance and at retrieval has a negative effect. Given
that VWM capacity depends on information load and the number of objects, the
positive effect of similarity may be attributed to reduced information load of
memory objects.
PMID- 26443897
TI - ?
PMID- 26443898
TI - ?
PMID- 26443899
TI - ?
PMID- 26443900
TI - Cell-free production of VDAC directly into liposomes for integration with
biomimetic membrane systems.
AB - The mitochondrial voltage-dependent anion channel (VDAC) is a pivotal protein
since it provides the major transport pathway between the cytosol and the
mitochondrial intermembrane space and it is implicated in cell apoptosis by
functioning as a gatekeeper for the trafficking of mitochondrial death molecules.
VDAC is a beta-barrel channel with a large conductance, and we use it as a model
transport protein for the design of biomimetic systems. To overcome the
limitations of classical overexpression methods for producing and purifying
membrane proteins (MPs) we describe here the use of an optimized cell-free
system. In a one-step reaction VDAC is obtained directly integrated into
liposomes and purified by ultracentrifugation. We then combine proteoliposomes
with different bilayers models in order to validate VDAC insertion and
functionality. This VDAC biomimetic model is the first example validating the use
of a cell-free expression system for production of MPs into liposomes and
tethered bilayers as a toolbox to build a wide range of biomimetic devices.
PMID- 26443901
TI - A Virtual Reality.
PMID- 26443904
TI - Ten Questions With . . .
PMID- 26443906
TI - Ask George.
PMID- 26443907
TI - The Rise of Telehealth: 'Triple Aim,' Innovative Technology, and Popular Demand
Are Spearheading New Models of Health and Wellness Care.
PMID- 26443908
TI - A Roundtable Discussion: Combination Products: Twice the Challenge?
AB - Combination products are therapeutic or diagnostic medical products that combine
drugs, devices, and/or biological products with one another. FDA developed a
regulation (final rule) on Current Good Manufacturing Practices (CGMP) for
combination products that became effective July 22, 2013 (21 CFR Part 4). AAMI
recently developed a technical information report (TIR) that provides information
on how to effectively implement FDA's regulation. The overall goal of the TIR is
to aid informed, risk-based decisions in establishing CGMP operating systems that
support development, manufacture, premarket regulatory evaluation, and ultimately
commercialization of combination products. This article, a result of an
discussion with industry and FDA representatives, explores the landscape of
combination products, highlights important considerations in developing and
seeking marketing clearance for these innovative products, and provides insight
on trends in the area.
PMID- 26443909
TI - Special Series: A Clinical Engineer's Approach To CMS Compliance.
PMID- 26443910
TI - Shuren Says Patients Are 'The Heart' of CDRH Focus.
PMID- 26443911
TI - Two-Man Biomed Team Adds Bed/Stretcher Maintenance to Arsenal.
PMID- 26443912
TI - Repairing Surgical Table Requires Extreme Caution.
PMID- 26443914
TI - Why Every Manager Should Take the CHTM Examination.
PMID- 26443916
TI - Lessons in Leadership.
PMID- 26443915
TI - Evaluating Device Design and Cleanability of Orthopedic Device Models
Contaminated with a Clinically Relevant Bone Test Soil.
AB - Reusable medical devices need to be cleaned prior to disinfection or
sterilization and subsequent use to prevent infections. The cleanability of
medical devices depends in part on the design of the device. This study examined
how models of orthopedic medical devices of increasing complexity retain calcium
phosphate bone cement, a relevant test soil for these devices. METHODS: The dye
Alizarin Red S and micro-computed tomography (MUCT) were used to assess the
amount and location of bone cement debris in a series of model orthopedic
devices. Testing was performed after soiling and cleaning once, and soiling and
cleaning 10 times. RESULTS: The color change of the dye after reacting with the
bone cement was useful for indicating the presence of bone cement in these
models. High-resolution MUCT analysis provided the volume and location of the
bone cement. Models that were more complex retained significantly more bone
debris than simpler designs. Model devices repeatedly soiled and cleaned 10 times
retained significantly more bone debris than those soiled and cleaned once.
CONCLUSION: Significantly more bone cement was retained in the more complex lumen
structures. This information may be useful in designing reusable orthopedic
devices, and other complex medical devices with lumens.
PMID- 26443918
TI - Magneto-Structural Correlations in a Series of Pseudotetrahedral [Co(II)(XR)4](2
) Single Molecule Magnets: An ab Initio Ligand Field Study.
AB - Over the past several decades, tremendous efforts have been invested in finding
molecules that display slow relaxation of magnetization and hence act as single
molecule magnets (SMMs). While initial research was strongly focused on
polynuclear transition metal complexes, it has become increasingly evident that
SMM behavior can also be displayed in relatively simple mononuclear transition
metal complexes. One of the first examples of a mononuclear SMM that shows a slow
relaxation of the magnetization in the absence of an external magnetic field is
the cobalt(II) tetra-thiolate [Co(SPh)4](2-). Fascinatingly, substitution of the
donor ligand atom by oxygen or selenium dramatically changes zero-field splitting
(ZFS) and relaxation time. Clearly, these large variations call for an in-depth
electronic structure investigation in order to develop a qualitative
understanding of the observed phenomena. In this work, we present a systematic
theoretical study of a whole series of complexes (PPh4)2[Co(XPh)4] (X = O, S, Se)
using multireference ab initio methods. To this end, we employ the recently
proposed ab initio ligand field theory, which allows us to translate the ab
initio results into the framework of ligand field theory. Magneto-structural
correlations are then developed that take into account the nature of metal-ligand
covalent bonding, ligand spin-orbit coupling, and geometric distortions away from
pure tetrahedral symmetry. The absolute value of zero-field splitting increases
when the ligand field strength decreases across the series from O to Te. The zero
field splitting of the ground state of the hypothetical [Co(TePh)4](2-) complex
is computed to be about twice as large as for the well-known (PPh4)2[Co(SPh)4]
compound. It is shown that due to the pi-anisotropy of the ligand donor atoms (S,
Se) magneto-structural correlations in [Co(OPh)4](2-) complex differ from
[Co(S/SePh)4](2-). In the case of almost isotropic OPh ligand, only variations in
the first coordination sphere affect magnetic properties, but in the case of
S/SePh ligand, variations in the first and second coordination sphere become
equally important for magnetic properties.
PMID- 26443919
TI - UV-Light-Induced Improvement of Fluorescence Quantum Yield of DNA-Templated Gold
Nanoclusters: Application to Ratiometric Fluorescent Sensing of Nucleic Acids.
AB - The use of DNA as a template has been demonstrated as an effective method for
synthesizing different-sized silver nanoclusters. Although DNA-templated silver
nanoclusters show outstanding performance as fluorescent probes for chemical
sensing and cellular imaging, the synthesis of DNA-stabilized gold nanoclusters
(AuNCs) with high fluorescence intensity remains a challenge. Here a facile,
reproducible, scalable, NaBH4-free, UV-light-assisted method was developed to
prepare AuNCs using repeats of 30 adenosine nucleotides (A30). The maximal
fluorescence of A30-stabilized AuNCs appeared at 475 nm with moderate quantum
yield, two fluorescence lifetimes, and a small amount of Au(+) on the surface of
the Au core. Results of size-exclusion chromatography revealed that A30
stabilized AuNCs were more compact than A30. A series of control experiments
showed that UV light played a dual role in the reduction of gold-ion precursors
and the decomposition of citrate ions. A30 also acted as a stabilizer to prevent
the aggregation of AuNCs. In addition, single-stranded DNA (ssDNA) consisting of
an AuNC-nucleation sequence and a hybridization sequence was utilized to develop
a AuNC-based ratiometric fluorescent probe in the presence of the double-strand
chelating dye SYBR Green I (SG). Under conditions of single-wavelength
excitation, the combination of AuNC/SG-bearing ssDNA and perfectly matched DNA
emitted fluorescence at 475 and 525 nm, respectively. The formed AuNC/SG-bearing
ssDNA enabled the sensitive, selective, and ratiometric detection of specific
nucleic acid targets. Finally, the AuNC-based ratiometric probes were
successfully applied to determine specific nucleic acid targets in human serum.
PMID- 26443920
TI - Structure and Absolute Configuration of Jurassic Polyketide-Derived Spiroborate
Pigments Obtained from Microgram Quantities.
AB - Complete structural elucidation of natural products is often challenging due to
structural complexity and limited availability. This is true for present-day
secondary metabolites, but even more for exceptionally preserved secondary
metabolites of ancient organisms that potentially provide insights into the
evolutionary history of natural products. Here, we report the full structure and
absolute configuration of the borolithochromes, enigmatic boron-containing
pigments from a Jurassic putative red alga, from samples of less than 50 MUg
using microcryoprobe NMR, circular dichroism spectroscopy, and density functional
theory calculations and reveal their polyketide origin. The pigments are
identified as spiroborates with two pentacyclic sec-butyl-trihydroxy-methyl
benzo[gh]tetraphen-one ligands and less-substituted derivatives. The
configuration of the sec-butyl group is found to be (S). Because the exceptional
benzo[gh]tetraphene scaffold is otherwise only observed in the recently
discovered polyketide clostrubin from a present-day Clostridium bacterium, the
Jurassic borolithochromes now can be unambiguously linked to the modern
polyketide, providing evidence that the fossil pigments are almost originally
preserved secondary metabolites and suggesting that the pigments in fact may have
been produced by an ancient bacterium. The borolithochromes differ fundamentally
from previously described boronated polyketides and represent the first boronated
aromatic polyketides found so far. Our results demonstrate the potential of
microcryoprobe NMR in the analysis of previously little-explored secondary
metabolites from ancient organisms and reveal the evolutionary significance of
clostrubin-type polyketides.
PMID- 26443921
TI - Investigations of the effect of nonmagnetic Ca substitution for magnetic Dy on
spin-freezing in Dy2Ti2O7.
AB - Physical properties of partially Ca substituted hole-doped Dy2Ti2O7 have been
investigated by ac magnetic susceptibility chi(ac)(T), dc magnetic susceptibility
chi(T), isothermal magnetization M(H) and heat capacity C(p)(T) measurements on
Dy1.8Ca0.2Ti2O7. The spin-ice system Dy2Ti2O7 exhibits a spin-glass type freezing
behavior near 16 K. Our frequency dependent chi(ac)(T) data of Dy1.8Ca0.2Ti2O7
show that the spin-freezing behavior is significantly influenced by Ca
substitution. The effect of partial nonmagnetic Ca(2+) substitution for magnetic
Dy(3+) is similar to the previous study on nonmagnetic isovalent Y(3+)
substituted Dy(2-x)Y(x) Ti2O7 (for low levels of dilution), however the
suppression of spin-freezing behavior is substantially stronger for Ca than Y.
The Cole-Cole plot analysis reveals semicircular character and a single
relaxation mode in Dy1.8Ca0.2Ti2O7 as for Dy2Ti2O7. No noticeable change in the
insulating behavior of Dy2Ti2O7 results from the holes produced by 10% Ca(2+)
substitution for Dy(3+) ions.
PMID- 26443923
TI - Functional evaluation of gene silencing on macrophages derived from U937 cells
using interference RNA (shRNA) in a model of macrophages infected with Leishmania
(Viannia) braziliensis.
AB - Leishmaniasis development is multifactorial; nonetheless, the establishment of
the infection, which occurs by the survival and replication of the parasite
inside its main host cell, the macrophage, is mandatory. Thus, the importance of
studying the molecular mechanisms involved in the Leishmania-macrophage
interaction is highlighted. The aim of this study was to characterize a cellular
model of macrophages derived from U937 cells that would allow for the
identification of infection phenotypes induced by genetic silencing with
interference RNA in the context of macrophages infected with Leishmania (Viannia)
braziliensis. The model was standardized by silencing an exogenous gene (gfp), an
endogenous gene (lmna) and a differentially expressed gene between infected and
non-infected macrophages (gro-beta). The silencing process was successful for the
three genes studied, obtaining reductions of 88.9% in the GFP levels, 87.5% in
LMNA levels and 74.4% for Gro-beta with respect to the corresponding control cell
lines. The cell model revealed changes in the infection phenotype of the
macrophages in terms of number of amastigotes per infected macrophage, number of
amastigotes per sampled macrophage and percentage of infected macrophages as a
result of gene silencing. Thus, this cell model constitutes a research platform
for the study of parasite-host interactions and for the identification of
potentially therapeutic targets.
PMID- 26443922
TI - Design, Synthesis and Structure-Activity Relationship Optimization of Lycorine
Derivatives for HCV Inhibition.
AB - Lycorine is reported to be a multifunctional compound. We previously showed that
lycorine is an HCV inhibitor with strong activity. Further research on the
antivirus mechanism indicated that lycorine does not affect the enzymes that are
indispensable to HCV replication but suppresses the expression of Hsc70 in the
host cell to limit HCV replication. However, due to the cytotoxicity and
apoptosis induction of lycorine, lycorine is unsafe to be a anti-HCV agent for
clinical application. As a result of increasing interest, its structure was
optimized for the first time and a novel series of lycorine derivatives was
synthesized, all of which lost their cytotoxicity to different degrees. Structure
activity analysis of these compounds revealed that disubstitution on the free
hydroxyl groups at C1 and C2 and/or degradation of the benzodioxole group would
markedly reduce the cytotoxicity. Furthermore, an alpha, beta-unsaturated ketone
would improve the HCV inhibitory activity of lycorine. The C3-C4 double bond is
crucial to the anti-HCV activity because hydrogenation of this double bond
clearly weakened HCV inhibition.
PMID- 26443924
TI - "I'm scared of being like mum": The Experience of Adolescents Living in Families
with Huntington Disease.
AB - BACKGROUND: The debilitating and very visible motor effects of the incurable,
progressive, and fatal neurodegenerative condition Huntington disease (HD) are
accompanied by more insidious cognitive, behavioural and personality disturbance.
The usual age of HD onset exposes children and adolescents to the natural history
of the condition as it affects a parent. This group of young people has been
largely overlooked in most research, which has concentrated upon the experiences
of affected individuals and their partners. OBJECTIVE: This study explores the
psychosocial context of young people living in families affected by HD, to better
understand their experiences and the specific challenges they face. METHOD: Ten
young people from five unrelated families affected by HD separately participated
in semi-structured individual interviews. At the time of interview, nine were
less than 18 years of age, and none had requested a predictive genetic test.
RESULTS: The young people demonstrated a depth of insight in their descriptions
of complex and often painful family circumstances. In addition to the tasks and
challenges associated with typical adolescent development, young people from
families affected by Huntington disease recognize that they face greater
responsibilities and stresses. CONCLUSION: This study highlights areas of unmet
needs for young people living in families affected by HD. Best practice HD care
should include consideration of the needs of young people in the family, and
offer developmentally appropriate HD education, prospective orientation to
genetic services, and psychological and social support.
PMID- 26443925
TI - Abnormal Weight and Body Mass Index in Children with Juvenile Huntington's
Disease.
AB - BACKGROUND AND OBJECTIVES: The hallmark clinical manifestation of Huntington's
disease (HD), namely lower weight and BMI has been reported in prodromal HD
(PreHD) adults and also in PreHD children. Here, we aim to evaluate
anthropometric measures of growth and development (height, weight, body mass
index (BMI)) in a group of children, adolescents, and young adults diagnosed with
Juvenile Onset Huntington's Disease (JHD). METHODS: Growth measures for 18 JHD
patients, documented prior to or shortly after diagnosis, were obtained through
medical records. JHD growth measures were compared to a large sample (n = 274) of
healthy children, as well as the Center for Disease Control (CDC) growth norms.
RESULTS: After controlling for sex and age, the JHD subjects had no significant
differences in height. However, they were an average of 10% lower than controls
in weight and BMI. Using CDC norms, the JHD subjects had the same pattern of
normal height but decrement in weight. Length of cytosine-adenine-guanine (CAG)
repeat in the huntingtin gene was significantly correlated to measures of weight
with longer CAG repeats being associated with more severe weight reduction. A
subset of 4 subjects had measures that pre-dated onset of any symptom and were
therefore prodromal JHD (preJHD). These subjects also had a significant decrement
in BMI compared to CDC norms. CONCLUSIONS: Children with JHD have normal height,
but significantly reduced weight and BMI, indicative of a specific deficit in
body weight. As the preJHD subjects were also low in BMI, this suggests that
these changes are directly due to the effect of the mutated gene on development,
rather than symptom manifestation of the disease itself. Potential mechanisms of
the weight decrement include energy deficiency due to mitochondrial dysfunction
during development.
PMID- 26443927
TI - Stereoselective Construction of 2,7-Disubstituted fused-Bis Tetrahydrofuran
Skeletons: Biomimetic-Type Synthesis and Biological Evaluation of (+/-)- and (-)
Aplysiallene and Their Derivatives.
AB - A series of trans/trans and cis/cis fused-bis tetrahydrofuran compounds have been
obtained stereoselectively in high yields via a one-pot operation involving the
intramolecular haloetherification of (Z,Z)-diene diol 19a and (E,E)-diene
disilylether 19d, respectively. This method was subsequently applied to the
biomimetic-type synthesis of (+/-)- and (-)-aplysiallene. The inhibitory
activities of these compounds and their bromodiene isomers toward Na(+)/K(+)
ATPase were determined in vitro, and gave IC50 values of approximately 15 MUM in
all cases.
PMID- 26443928
TI - The role of working memory and verbal fluency in autobiographical memory in early
Alzheimer's disease and matched controls.
AB - Retrieval of autobiographical memories (AMs) is important for "sense of self".
Previous research and theoretical accounts suggest that working memory (WM) and
semantic and phonemic fluency abilities facilitate the hierarchical search for,
and reliving of past, personal events in the mind's eye. However, there remains a
lack of consensus as to the nature of the relationships between these cognitive
functions and the truly episodic aspects of AM. The present study therefore aimed
to explore the associations between these variables in a sample with a wide range
of cognitive abilities. The study incorporated a between-groups component, and a
correlational component with multiple regression. Participants with Alzheimer's
disease (n=10) and matched healthy controls (n=10) were assessed on measures of
semantic and episodic AM search and retrieval, auditory and spatial WM, and
semantic and phonemic fluency. The AD group produced less episodic AM content
compared to controls. Semantic fluency predicted episodic AM retrieval
independent of age effects but there were no significant relationships between
measures of phonemic fluency, WM and episodic AM. The results suggest that the
ability to maintain hierarchical search of the semantic knowledge-base is
important for truly episodic reliving, and interventions for people with AM
impairment might therefore benefit from incorporating structured, individualised
external memory-aids to facilitate AM search and retrieval.
PMID- 26443929
TI - Reply to beta blockers in epithelial ovarian cancer and beta-blockers and
improved survival from ovarian cancer: New miracle treatment or another case of
immortal person-time bias?
PMID- 26443926
TI - Neuropsychiatry and White Matter Microstructure in Huntington's Disease.
AB - BACKGROUND: Neuropsychiatric symptoms in Huntington's disease (HD) are often
evident prior to clinical diagnosis. Apathy is highly correlated with disease
progression, while depression and irritability occur at different stages of the
disease, both before and after clinical onset. Little is understood about the
neural bases of these neuropsychiatric symptoms and to what extent those neural
bases are analogous to neuropsychiatric disorders in the general population.
OBJECTIVE: We used Diffusion Tensor Imaging (DTI) to investigate structural
connectivity between brain regions and any putative microstructural changes
associated with depression, apathy and irritability in HD. METHODS: DTI data were
collected from 39 premanifest and 45 early-HD participants in the Track-HD study
and analysed using whole-brain Tract-Based Spatial Statistics. We used regression
analyses to identify white matter tracts whose structural integrity (as measured
by fractional anisotropy, FA) was correlated with HADS-depression, PBA-apathy or
PBA-irritability scores in gene-carriers and related to cumulative probability to
onset (CPO). RESULTS: For those with the highest CPO, we found significant
correlations between depression scores and reduced FA in the splenium of the
corpus callosum. In contrast, those with lowest CPO demonstrated significant
correlations between irritability scores and widespread FA reductions. There was
no significant relationship between apathy and FA throughout the whole brain.
CONCLUSIONS: We demonstrate that white matter changes associated with both
depression and irritability in HD occur at different stages of disease
progression concomitant with their clinical presentation.
PMID- 26443932
TI - Exploring Safe Sleep and SIDS Risk Perception in an African-American Community:
Focused Ethnography.
AB - OBJECTIVES: Explore the cultural influences of safe sleep practices by African
American caregivers of children under 2 years old. Explore the role of health
care professionals in promoting safe sleep. DESIGN AND SAMPLE: A focused
ethnography was used to understand the contextual cultural meaning and
experiences of safe sleep practices of African-American caregivers of children
under 2 years. Nineteen African-Americans participated in this study. MEASURES:
Demographic data were collected and semi-structured interviews were conducted
with individuals and small groups. Saturation of the data occurred after 17
interviews. Data were analyzed using Leininger's four Phases of qualitative data
analysis. RESULTS: (Themes): (1) The informants expressed both accurate and
inaccurate knowledge of Sudden Infant Death Syndrome (SIDS) and safe sleep
practices influenced by personal experiences, hospital education, family,
extended family and television; (2) Sleeping with infants and children was viewed
as a cultural caring behavior promoting comfort, closeness and protection for
infants, children, parents and caregivers; (3) The informants want and are
seeking collaboration with nurses and health care professionals who are viewed as
important in promoting accurate information about SIDS and safe sleep practices.
CONCLUSION: The role of the nurse can impact accurate outcomes about SIDS and
safe sleep practices.
PMID- 26443930
TI - Stem cell therapy for cardiac regeneration: hits and misses.
AB - Cardiac injury and loss of cardiomyocytes is a causative as well as a resultant
condition of cardiovascular disorders, which are the leading cause of death
throughout the world. This loss of cardiomyocytes cannot be completely addressed
through the currently available drugs being administered, which mainly function
only in relieving the symptoms. There is a huge potential being investigated for
regenerative and cell replacement therapies through recruiting stem cells of
various origins namely embryonic, reprogramming/induction, and adult tissue.
These sources are being actively studied for translation to clinical scenarios.
In this review, we attempt to discuss some of these promising scenarios,
including the clinical trials and the obstacles that need to be overcome, and
hope to address the direction in which stem cell therapy is heading.
PMID- 26443933
TI - Effects of lip-closing training on maximum voluntary lip-closing force during lip
pursing in healthy young adults.
AB - To investigate the effect of lip-closing training, the time-course of
multidirectional lip-closing forces during training was evaluated. The subjects
were healthy young adults with no systemic disease. Ten subjects each were
allocated to the training and non-training (control) groups. The subjects were
instructed to use a lip muscle strength fixation device (M Patakara) for lip
closing training. Regarding closing the upper and lower lips against this force
for 3 min as one task, the subjects were instructed to perform three tasks a day
for 4 weeks. The multidirectional lip-closing forces were measured before, during
and after training every week. In the control group, the forces were measured
under the same schedule without training. After the initiation of training, the
total lip-closing force significantly increased at 3 and 4 weeks in the training
group compared with that in the control group (P = 0.003 at 3 weeks, P < 0.001 at
4 weeks). After the completion of training, the force decreased from 1 week and
no significant difference from the control group was noted. When the lip-closing
force was evaluated by direction, significant increases in the upward and
downward directions were noted in the training group compared with those in the
control group (P = 0.034 at 3 weeks for upwards; P = 0.027 at 4 weeks for
downwards). Quantitative analysis confirmed that lip-closing training enhanced
the lip-closing force regionally.
PMID- 26443934
TI - Mediation Analysis of Hepatitis B and C in Relation to Hepatocellular Carcinoma
Risk.
AB - BACKGROUND: Hepatitis B and C viruses are well-established risk factors for
hepatocellular carcinoma (HCC) but their coordinated etiologic mechanism remains
unclear. We aimed to assess the mediation effect of the two viruses on HCC risk.
METHODS: We conducted a prospective cohort study in Taiwan (R.E.V.E.A.L.
Hepatitis B Virus study), which included 3,851 participants seropositive for
hepatitis B surface antigen and 278 incident HCC cases. Serum samples at
enrollment or follow-up were tested for seromarkers and viral load of hepatitis B
(HBV) and C (HCV). Mediation analyses for HCC risk were performed using Cox
proportional hazards and linear regression models. RESULTS: Among participants
with chronic hepatitis B, the direct effect of anti-HCV serostatus (positive vs.
negative) independent of HBV viral load was associated with increased risk of HCC
with a hazard ratio (HR) of 2.5 (95% confidence interval [CI] = 1.7, 3.6), and
the indirect effect mediated through suppressing HBV viral load decreased the HCC
risk with an HR of 0.75 (95% CI = 0.67, 0.84). Opposite effects led to an
attenuated marginal effect with an HR of 1.7 (95% CI = 1.2, 2.5). For an increase
in HCV viral load from 800 to 404,000 IU/ml (minimum to median viral level), the
HRs were 1.6 (95% CI = 1.2, 2.0) for the direct effect, 0.78 (95% CI = 0.72,
0.85) for the indirect effect, and 1.1 (95% CI = 0.89, 1.5) for the marginal
effect. CONCLUSION: The results support a suppressive effect of HCV on HCC risk
mediated through HBV viral load and an adverse direct effect.
PMID- 26443935
TI - The Transition of Medical Students Through Residency: Effects on Physical
Activity and Other Lifestyle-Related Behaviors.
AB - BACKGROUND: Little is known about lifestyle choices and preventive healthcare
seeking behaviors during the transition from medical school graduation to
residency training, a period characterized by increased rates of stress and lack
of free time due to demanding working conditions. All of these issues are likely
to affect physical activity (PA) level. This study explored the evolution of PA
and other lifestyle behaviors during this transition. METHODS: A cross-sectional
study and a cohort study were conducted with medical students (2010) and
physicians before and after the first year of residency (2013 and 2014). A self
administered questionnaire assessed PA, health and lifestyle behaviors. RESULTS:
From a sample of 420 medical students and 478 residents, 74% comply with current
PA guidelines. PA decreased by 16% during residency. Low levels of PA were found
among (i) females and in respondents who reported (ii) poor self-perceived health
and (iii) unhealthy body weight (P < .05). Low PA level was also significantly
associated with poor mental health in first-year residents. CONCLUSIONS: The
transition has a negative effect on physicians' PA level that may affect
physicians' own health and patient care. Medical programs should encourage
residents to engage in PA to assure physicians' personal and mental health.
PMID- 26443936
TI - Frequency of Surgery Cancellations Associated With Myocardial Infarction or Death
6 Months After Coronary Stent Placement.
PMID- 26443937
TI - The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with
reduced insulin secretion and increased insulin sensitivity in Italian obese
subjects.
AB - BACKGROUND: Perilipin 2 (PLIN2), a member of the family of perilipin lipid
droplets coating proteins, is very widely expressed. The Ser251Pro (rs35568725)
missense mutation in exon 6 of PLIN2 gene was previously associated with
increased lipid accumulation, decreased lipolysis and increased number of small
lipid droplets per cell. Furthermore, the Pro251 mutation was associated with
decreased plasma triglyceride and very low density lipoprotein concentrations in
population studies. The aim of this study was to evaluate the effect of the
Ser251Pro mutation of PLIN2 gene in a cohort with a higher predisposition to
obesity-associated metabolic alterations, such as insulin resistance, decreased
insulin-secretion, hyperglycaemia, and dyslipidaemia. METHODS: A large cohort (N
= 1692) of Italian obese subjects (mean body mass index = 41 kg/m(2) ) was
genotyped for the Ser251Pro mutation. All participants underwent oral glucose
tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices
of insulin resistance and of insulin secretion were also calculated. Clinical and
biochemical parameters were collected for all participants. RESULTS: We observed
that insulin concentration was significantly reduced at 120 min after the
administration of glucose in Pro251 allele carriers, whereas glucose levels were
similar in Pro251 allele carriers and non-carriers throughout the OGTT.
Furthermore, the CIR120 index of insulin secretion was significantly lower (P <
0.035) and the ISI index of insulin-sensitivity was significantly higher (P <
0.031) in carriers of the Pro251 allele. When we analysed men and women
separately to test for gender-specific associations, we observed that in women
insulin levels were significantly lower in Pro251 allele carriers compared with
wild-type subjects throughout the whole OGTT. In men, we confirmed a significant
reduction in insulin concentration only at 120 min after the OGTT. No significant
differences between genotype groups regarding triglyceride levels and anyother
clinical and metabolic parameters were observed. CONCLUSION: We observed a strong
significant association between the PLIN2 Pro251 mutation and lower insulin
secretion associated with an increased insulin sensitivity. Copyright (c) 2015
John Wiley & Sons, Ltd.
PMID- 26443938
TI - Effects of passive and active movement on vibrotactile detection thresholds of
the Pacinian channel and forward masking.
AB - We investigated the gating effect of passive and active movement on the
vibrotactile detection thresholds of the Pacinian (P) psychophysical channel and
forward masking. Previous work on gating mostly used electrocutaneous stimulation
and did not allow focusing on tactile submodalities. Ten healthy adults
participated in our study. Passive movement was achieved by swinging a platform,
on which the participant's stimulated hand was attached, manually by a trained
operator. The root-mean-square value of the movement speed was kept in a narrow
range (slow: 10-20 cm/s, fast: 50-60 cm/s). Active movement was performed by the
participant him-/herself using the same apparatus. The tactile stimuli consisted
of 250-Hz sinusoidal mechanical vibrations, which were generated by a shaker
mounted on the movement platform and applied to the middle fingertip. In the
forward-masking experiments, a high-level masking stimulus preceded the test
stimulus. Each movement condition was tested separately in a two-interval forced
choice detection task. Both passive and active movement caused a robust gating
effect, that is, elevation of thresholds, in the fast speed range. Statistically
significant change of thresholds was not found in slow movement conditions.
Passive movement yielded higher thresholds than those measured during active
movement, but this could not be confirmed statistically. On the other hand, the
effect of forward masking was approximately constant as the movement condition
varied. These results imply that gating depends on both peripheral and central
factors in the P channel. Active movement may have some facilitatory role and
produce less gating. Additionally, the results support the hypothesis regarding a
critical speed for gating, which may be relevant for daily situations involving
vibrations transmitted through grasped objects and for manual exploration.
PMID- 26443939
TI - Structural heart interventions training in Europe.
AB - BACKGROUND: Structural heart interventions have made major strides over the last
years with the introduction of TAVR, percutaneous mitral valve repair and adult
congenital heart disease procedures. METHODS: As part of the SCAI SHD Early
Career Task Force committee, we complied a survey of 17 questions using a Survey
Monkey website. We sent invitations twice by email to 183 European program
directors of interventional cardiology fellowship programs in Europe. RESULTS:
The most commonly performed procedures performed by the fellows were transseptal
punctures, TAVR, BAV, PFO and BMV. For the rest of the structural procedures,
each fellow performed <10 procedures during their training. CONCLUSION:
Structural heart interventions training will keep expanding over the next years
with the introduction of newer devices and techniques and accumulation of
experience. Given the small number of the more rare structural procedures, it
becomes apparent that we need to design national or international training
networks to provide adequate training experience to all trainees.
PMID- 26443940
TI - [Editor's Comment].
PMID- 26443941
TI - [Core needle biopsy].
PMID- 26443942
TI - [Not Available].
PMID- 26443943
TI - [Not Available].
PMID- 26443944
TI - [Postoperative care].
PMID- 26443945
TI - Clinical roles and applications of progesterone in reproductive medicine: an
overview.
AB - The physiologic and clinical value of progesterone is undisputed and a
cornerstone of human reproduction. Better understanding of the exact dynamics and
effects of endogenous progesterone secretion, as well as its therapeutic actions,
is critical to ensure optimal clinical results in artificial reproduction
technology, and to enhance chances of successfully completing pregnancy. Novel
progesterone-based drugs and administration regimens will provide clinicians with
greater options to make the management and treatment of infertile couples less
burdensome and more successful.
PMID- 26443946
TI - Biological pretreatment of rice straw with Streptomyces griseorubens JSD-1 and
its optimized production of cellulase and xylanase for improved enzymatic
saccharification efficiency.
AB - Biological pretreatment of rice straw and production of reducing sugars by
hydrolysis of bio-pretreated material with Streptomyces griseorubens JSD-1 was
investigated. After 10 days of incubation, various chemical compositions of
inoculated rice straw were degraded and used for further enzymatic hydrolysis
studies. The production of cellulolytic enzyme by S. griseorubens JSD-1 favored
the conversion of cellulose to reducing sugars. The culture medium for
cellulolytic enzyme production by using agro-industrial wastes was optimized
through response surface methodology. According to the response surface analysis,
the concentrations of 11.13, 20.34, 4.61, and 2.85 g L(-1) for rice straw, wheat
bran, peptone, and CaCO3, respectively, were found to be optimum for cellulase
and xylanase production. Then the hydrolyzed spent Streptomyces cells were used
as a nitrogen source and the maximum filter paper cellulase,
carboxymethylcellulase, and xylanase activities of 25.79, 78.91, and 269.53 U mL(
1) were achieved. The crude cellulase produced by S. griseorubens JSD-1 was
subsequently used for the hydrolysis of bio-pretreated rice straw, and the
optimum saccharification efficiency of 88.13% was obtained, indicating that the
crude enzyme might be used instead of commercial cellulase during a
saccharification process. These results give a basis for further study of
bioethanol production from agricultural cellulosic waste.
PMID- 26443947
TI - RUPTURES IN THE ANALYTIC SETTING AND DISTURBANCES IN THE TRANSFORMATIONAL FIELD
OF DREAMS.
AB - This paper explores some implications of Bleger's (1967, 2013) concept of the
analytic situation, which he views as comprising the analytic setting and the
analytic process. The author discusses Bleger's idea of the analytic setting as
the depositary for projected painful aspects in either the analyst or patient or
both-affects that are then rendered as nonprocess. In contrast, the contents of
the analytic process are subject to an incessant process of transformation (Green
2005). The author goes on to enumerate various components of the analytic
setting: the nonhuman, object relational, and the analyst's "person" (including
mental functioning). An extended clinical vignette is offered as an illustration.
PMID- 26443948
TI - "I HEAR MY VOICE, BUT WHO IS TALKING?": UNDERSTANDING DEPERSONALIZATION.
AB - Depersonalization is the frightening experience of being a shut-inside,
ghostlike, "true" self that observes another part of the self interacting in the
outside world. The "true" self hides safely within, while the "participating"
self holds all affects and impulses. This split in the ego is created via
internal projective identification in the face of overwhelming affect,
unavailability of adequate identifications, and insufficient support for psychic
cohesion. As the transference develops, the powerful entrapping cocoon of
depersonalization can be projected onto the now-entrapping analyst, where it can
be addressed. A clinical vignette illustrates these points.
PMID- 26443949
TI - HANSEL AND GRETEL: A TALE OF TERROR.
AB - In the analysis of a woman with multiple childhood traumas, the fairy tale
"Hansel and Gretel" figured prominently. The author discusses the use of the
fairy tale in this case at various levels. He suggests an interplay between a
national myth, the fairy tale, and a personal myth-the patient's psychodynamics.
The fairy tale can be used to illuminate personal meanings derived from it. In
the experience of childhood trauma, the repeated reading of a fairy tale can help
organize and defend against terrifying anxiety.
PMID- 26443950
TI - ATTACKS ON LINKING OR A DRIVE TO COMMUNICATE? TOLERATING THE PARADOX.
AB - The notion of attacks on linking, as described by Bion, may depict a patient's
drive to communicate the internalization of a destructive relationship between a
primary object and an infant. This may be enacted between patient and analyst in
the here and now of the analysis, whereby fragmentation and numbing of thinking
may point to a primitive catastrophe relived in the psychoanalytic setting. The
patient's material may seem incoherent, but incoherence might be the
communication the patient is unconsciously trying to convey. Thus, the notion of
attacks on linking depicts a paradoxical, caesural experience in which the attack
on linking is itself a link.
PMID- 26443951
TI - MOTILITY, AGGRESSION, AND THE BODILY I: AN INTERPRETATION OF WINNICOTT.
AB - Among the central ideas associated with the name of Winnicott, scant mention is
made of motility. This is largely attributable to Winnicott himself, who never
thematized motility and never wrote a paper specifically devoted to the topic.
This paper suggests both that the idea of motility is nonetheless of central
significance in Winnicott's thought, and that motility is of central importance
in the development and constitution of the bodily I. In elaborating both these
suggestions, the paper gives particular attention to the connections between
motility, continuity, aggression, and creativity in Winnicott's work.
PMID- 26443952
TI - "AFTER THE EVENT": FREUD'S UNCANNY AND THE ANXIETY OF ORIGINS.
AB - This essay aims to revise Freud's theory of the uncanny by rereading his own
essay of that name along with the key material Freud drew on in formulating his
theory: E. T. A. Hoffmann's short story "The Sandman" (1816a) and Ernst Jentsch's
essay "On the Psychology of the Uncanny" (1906a). While arguing, initially, both
that Jentsch's work is fundamentally misconstrued by Freud and that it offers a
better account of what happens in Hoffmann's story, the essay moves beyond
Jentsch's account to offer a more philosophically oriented theory of the uncanny,
one more in line with Freud's ideas in Beyond the Pleasure Principle (1920a).
PMID- 26443963
TI - Effects of Combined High Hydrostatic Pressure and Dense Phase Carbon Dioxide on
the Activity, Structure and Size of Polyphenoloxidase.
AB - High hydrostatic pressure (HHP) may activate undesirable enzymes such as
polyphenoloxidase (PPO). Carbon dioxide (CO2 ) addition to HHP could increase
enzyme inactivation. We investigated the inactivation of combined HHP and dense
phase carbon dioxide process on activity, secondary conformation and size of pure
PPO from mushroom. Solutions (2.35MUM, in phosphate buffer pH 6.8) were treated
with HHP alone (HHP), or 3.6% w/w of CO2 was injected into the package (HHP+CO2).
Treatment conditions were 600 MPa, 20 degrees C, for 1, 3, 5, 7, and 9 min.
HHP+CO2 treatment significantly decreased residual enzyme activity (REA) to 30%
to 12% after 1 to 9 min, respectively, whereas only HHP had no significant
effect. Both HHP and HHP+CO2 treatments caused changes in secondary
conformations, however HHP+CO2 changes were more extensive. Alpha-helix fractions
were reduced by 32% and 41%, while beta sheet, turn and unordered increased by
63% and 213%, 100% and 71%, and 118% and 82% for HHP and HHP+CO2, respectively
after 9 min. The protein size in HHP+CO2 samples was 5- to 6-fold larger than
that of Control and HHP treatment, and this increase was inversely correlated
with REA. The best inactivation kinetics of HHP+CO2 model was the 2-fractional
model with 2 simultaneous 1st-order steps, contributing 70% and 30% to original
enzyme activity, with k(labile) = 12.15 min(-1) and k(stable) = 0.07 min(-1),
respectively. No recovery in activity, secondary conformation and size in all
samples were observed after 1-mo storage. Addition of CO2 in HHP treatment can
improve enzyme inactivation, and therefore product shelf-life and quality.
PRACTICAL APPLICATION: High hydrostatic pressure (HHP) achieves the safety of
foods as a nonthermal method, but it may activate undesirable enzymes resulting
in short shelf life due to, for example flavor and color changes. Our study
determined that addition of CO2 to HHP has significant effects on enzyme
inactivation, secondary conformational and molecular size changes of mushroom
PPO. No recovery in activity, secondary conformation and size in all samples were
observed after 1 mo storage at 4 degrees C. This combined process increases
product shelf life, in addition to safety and nutrient preservation.
PMID- 26443964
TI - Anatomy and development of the cardiac lymphatic vasculature: Its role in injury
and disease.
AB - Lymphatic vessels are present throughout the entire body in all mammals and
function to regulate tissue fluid balance, lipid transport and survey the immune
system. Despite the presence of an extensive lymphatic plexus within the heart,
until recently the importance of the cardiac lymphatic vasculature and its
origins were unknown. Several studies have described the basic anatomy of the
developing cardiac lymphatic vasculature and more recently the detailed
development of the murine cardiac lymphatics has been documented, with important
insight into their cellular sources during embryogenesis. In this review we
initially describe the development of systemic lymphatic vasculature, to provide
the background for a comparative description of the spatiotemporal development of
the cardiac lymphatic vessels, including detail of both canonical, typically
venous, and noncanonical (hemogenic endothelium) cellular sources. Subsequently,
we address the response of the cardiac lymphatic network to myocardial infarction
(heart attack) and the therapeutic potential of targeting cardiac
lymphangiogenesis.
PMID- 26443965
TI - Coincidence of late-onset cytomegalovirus-induced myositis and gastritis in a
pediatric renal transplant recipient.
AB - An 8-year-old girl with a renal transplant was admitted for myalgia and muscle
weakness in both legs over the previous 2 weeks. She also had fever and
intermittent epigastric pain. Based on these clinical manifestations, and
laboratory and histopathological findings, the diagnosis was coincidence of late
onset cytomegalovirus (CMV)-induced myositis and gastritis in an
immunocompromised child with a renal transplant. After administration of
intravenous ganciclovir for 3 weeks, her symptoms resolved, with normalization of
abnormal muscle enzymes, including lactate dehydrogenase, creatine kinase,
aspartate aminotransferase, and the disappearance of CMV viremia.
PMID- 26443966
TI - Ultrasensitive self-powered cytosensors based on exogenous redox-free enzyme
biofuel cells as point-of-care tools for early cancer diagnosis.
AB - An exogenous redox-free, membrane-less enzyme biofuel cell-based ultrasensitive
self-powered cytosensing platform was fabricated. With the ultrahigh sensitivity
and the merits of not requiring external power sources or exogenous reagents, the
device has great potential as a point-of-care tool for early diagnosis of cancer
in vivo.
PMID- 26443967
TI - Visualization of Patients' Skin Lesions on Their Smartphones: A New Step During
Dermatology Visits.
PMID- 26443969
TI - Successful treatment with intravenous high-dose immunoglobulin for cardiomyopathy
in dermatomyositis complicated with rapid progressive interstitial pneumonia.
AB - Cardiomyopathy and rapid progressive interstitial pneumonia (IP) are potentially
fatal complications in polymyositis/dermatomyositis. We experienced a
dermatomyositis patient with multiple adverse prognostic factors, complicating
rapid progressive IP, macrophage activation syndrome (MAS), and cardiomyopathy.
IP and MAS improved with strong immunosuppressive therapy, despite which
cardiomyopathy developed. Therefore, we applied intravenous high-dose
immunoglobulin therapy (IVIg), and cardiac function improved dramatically. This
is the first report to present the effectiveness of IVIg for cardiomyopathy in
dermatomyositis.
PMID- 26443970
TI - The Diaza[5.5.6.6]fenestrane Skeleton-Synthesis of Leuconoxine Alkaloids.
AB - Among the Aspidosperma-derived monoterpene indole alkaloids, the leuconoxine
subgroup has drawn significant attention from the synthetic community during the
past few years. This Minireview summarizes the hitherto six completed total
syntheses of leuconoxines emphasizing the different strategies for assembling the
key structural motif, an unprecedented diaza[5.5.6.6]fenestrane skeleton. In
addition, the proposed biogenetic relationships within the group of these
alkaloids are described.
PMID- 26443971
TI - The role of sensitization in musculoskeletal shoulder pain.
AB - INTRODUCTION: Peripheral and central sensitization are neurophysiological
processes that can prolong painful conditions. Painful shoulder conditions are
often persistent, perhaps due to the presence of sensitization. METHOD: This
manuscript summarizes six studies that have evaluated those with musculoskeletal
shoulder pain for the presence of sensitization. RESULTS: All six manuscripts
report evidence of peripheral sensitization, while central sensitization was
described in five of the studies. The chronicity of symptoms in subjects who were
included in the studies is probably influencing this finding. The primary
somatosensory test used to assess sensitization in these studies was Pressure
Pain Threshold, a test for lowered nociceptive thresholds. DISCUSSION: It appears
that peripheral sensitization manifests consistently in those with
musculoskeletal shoulder pathology, probably due to the inflammatory processes
related to tissue injury. Central sensitization, while not universally present,
was reported in a majority of the manuscripts. Because central sensitization is
thought to be a key step on the pathway to chronic pain, evidence for its
presence in those with shoulder pain is significant. Clinicians should expect the
presence of sensitization with shoulder pathology and make appropriate choices
about interventions so as not to exacerbate pain.
PMID- 26443972
TI - Interval and continuous exercise enhances aerobic capacity and hemodynamic
function in CHF rats.
AB - OBJECTIVE: The aim of the present study was to compare the effects of continuous
versus interval aerobic exercise training on hemodynamic parameters, cardiac
remodeling, and maximal exercise capacity (MEC) in chronic heart failure (CHF)
rats. METHOD: Twenty-four male Wistar rats were subjected to myocardial
infarction (MI) surgery. Five weeks post MI, the animals were assigned to one of
three groups: sedentary group (CHF-Sed, n=8), aerobic continuous training group
(CHF-ACT, n=8), and aerobic interval training group (CHF-AIT, n=8). Treadmill
training was performed five times a week for 8 weeks (ACT: 50 min/day at 15 m/min
and AIT: 40 min/day with 8 min of warm-up at 10 m/min and exercise at 15 m/min
4*4 min interspersed with 4*4 min at 23 m/min). MEC was evaluated pre and post
exercise program. RESULTS: Left ventricular end-diastolic pressure (LVEDP), left
ventricular mass/body mass ratio (LVM:BM), and total collagen volume fraction
were lower in the trained groups compared with the sedentary group, but no
difference was found between the trained groups. Systolic ventricular pressure
(SVP) and maximum positive derivative of LV pressure (+dP/dtmax) were higher in
the trained groups, but CHF-ACT showed higher +dP/dt(max) compared to CHF-AIT.
Both training regimens were able to increase MEC. However, the aerobic interval
training was superior for improving MEC. CONCLUSION: Aerobic training is an
important intervention to improve cardiac function and remodeling and physical
capacity in CHF rats. Interval training is a potential strategy to maximize the
results, but exercise type and intensity are still topics to be explored.
PMID- 26443973
TI - Effects of nephrectomy on respiratory function and quality of life of living
donors: a longitudinal study.
AB - BACKGROUND: A living donor transplant improves the survival and quality of life
of a transplant patient. However, the impact of transplantation on postoperative
lung function and respiratory muscular strength in kidney donors remains unknown.
OBJECTIVE: To evaluate pulmonary function, respiratory muscle strength, quality
of life and the incidence of postoperative pulmonary complications (PPCs) in
kidney donors undergoing nephrectomy. METHOD: This prospective cohort enrolled
110 consecutive kidney donors undergoing nephrectomy. Subjects underwent
pulmonary function (using spirometry) and respiratory muscular strength (using
manovacuometry) assessments on the day prior to surgery and 1, 2, 3 and 5 days
postoperatively. Quality of life (measured by the SF-36) was evaluated
preoperatively and 30 days postoperatively. PPCs were assessed daily by a blinded
assessor. RESULTS: Donors exhibited a decrease of 27% in forced vital capacity,
58% in maximum inspiratory capacity and 51% in maximum expiratory pressure on the
1stpostoperative day (p<0.001) but this improved over days 2, 3 and 5 but had not
returned to preoperative levels. Patient quality of life was still impaired at 30
days with regards to functional capacity, physical role, pain, vitality and
social functioning (p<0.05) but these parameters improved slowly. None of the
patients developed PPCs. CONCLUSION: Kidney donors submitted to nephrectomy
exhibited a reduction in pulmonary function, respiratory muscular strength and
quality of life, most of which were improving toward pre-surgical levels.
PMID- 26443974
TI - Influence of obstructive sleep apnea syndrome in the fluctuation of the
submaximal isometric torque of knee extensors in patients with early-grade
osteoarthritis.
AB - OBJECTIVE: The aim of this study was to investigate whether obstructive sleep
apnea (OSA) alters the fluctuation of submaximal isometric torque of the knee
extensors in patients with early-grade osteoarthritis (OA). METHOD: The study
included 60 male volunteers, aged 40 to 70 years, divided into four groups: Group
1 (G1) - Control (n=15): without OA and without OSA; Group 2 (G2) (n=15): with OA
and without OSA; Group 3 (G3) (n=15): without OA and with OSA; and Group 4 (G4)
(n=15) with OA and with OSA. Five patients underwent maximal isometric
contractions of 10 seconds duration each, with the knee at 60 degrees of flexion
to determine peak torque at 60 degrees . To evaluate the fluctuation of torque, 5
submaximal isometric contractions (50% of maximum peak torque) of 10 seconds
each, which were calculated from the standard deviation of torque and coefficient
of variation, were performed. RESULTS: Significant differences were observed
between groups for maximum peak torque, while G4 showed a lower value compared
with G1 (p=0.005). Additionally, for the average torque exerted, G4 showed a
lower value compared to the G1 (p=0.036). However, no differences were found
between the groups for the standard deviation (p=0.844) and the coefficient of
variation (p=0.143). CONCLUSION: The authors concluded that OSA did not change
the parameters of the fluctuation of isometric submaximal torque of knee
extensors in patients with early-grade OA.
PMID- 26443975
TI - Reliability of new software in measuring cervical multifidus diameters and
shoulder muscle strength in a synchronized way; an ultrasonographic study.
AB - OBJECTIVES: This study was conducted with the purpose of evaluating the inter
session reliability of new software to measure the diameters of the cervical
multifidus muscle (CMM), both at rest and during isometric contractions of the
shoulder abductors in subjects with neck pain and in healthy individuals. METHOD:
In the present study, the reliability of measuring the diameters of the CMM with
the Sonosynch software was evaluated by using 24 participants, including 12
subjects with chronic neck pain and 12 healthy individuals. The anterior
posterior diameter (APD) and the lateral diameter (LD) of the CMM were measured
in a resting state and then repeated during isometric contraction of the shoulder
abductors. Measurements were taken on separate occasions 3 to 7 days apart in
order to determine inter-session reliability. Intraclass correlation coefficient
(ICC), standard error of measurement (SEM), and smallest detectable difference
(SDD) were used to evaluate the relative and absolute reliability, respectively.
RESULTS: The Sonosynch software has shown to be highly reliable in measuring the
diameters of the CMM both in healthy subjects and in those with neck pain. The
ICCs 95% CI for APD ranged from 0.84 to 0.94 in subjects with neck pain and from
0.86 to 0.94 in healthy subjects. For LD, the ICC 95% CI ranged from 0.64 to 0.95
in subjects with neck pain and from 0.82 to 0.92 in healthy subjects.
CONCLUSIONS: Ultrasonographic measurement of the diameters of the CMM using
Sonosynch has proved to be reliable especially for APD in healthy subjects as
well as subjects with neck pain.
PMID- 26443976
TI - Physiotherapy: a historical analysis of the transformation from an occupation to
a profession in Brazil.
AB - ABSTRACTBackground:Analyzing the historical and social path of an occupation
using the sociology of professions and the perspective of scientific knowledge
promotes an understanding of the origin of physical therapy in Brazil and of
discussions of the profession in its contemporary context. OBJECTIVE: The aim of
this paper was to discuss the professionalization process of physical therapy in
Sao Paulo. The authors tried to analyze bath therapy, massage therapy, and
physical therapy as occupations involving distinct expertise and as part of the
group of occupations that evolved into the profession of physiotherapy in the
first half of the twentieth century. METHOD: The analysis undertaken was a
qualitative study based on an analysis of historical documents. Eighty-six
professional records from the Service of Inspection of Professional Practice in
the state of Sao Paulo and healthcare legislation from the 1930s and 1940s were
analyzed. RESULTS: The distinction between physical therapy practitioner and
profession of physiotherapy can be seen by examining registration requirements
for rank-and-file nurses with expertise in interactions; this distinction
suggests the emergence of specialized expertise that was clearly a part of
neither medicine nor nursing and contributed to expertise in physical therapy
since the 1950s. CONCLUSION: The regulation of physiotherapy practices, the
recognition of expertise, the accreditation of practical nurses by the State, and
the institutionalization of a course for physical therapy practitioners in 1951
are key elements of the professionalization process for the physical therapy
profession in Brazil.
PMID- 26443977
TI - Evidence-Based Practice: a survey regarding behavior, knowledge, skills,
resources, opinions and perceived barriers of Brazilian physical therapists from
Sao Paulo state.
AB - BACKGROUND: Evidence-Based Practice (EBP) has been widely used by health
professionals. However, no study in Brazil has investigated the data regarding
the knowledge and difficulties related to EBP from a representative sample of
physical therapists. OBJECTIVE: To identify behavior, knowledge, skills,
resources, opinions and perceived barriers of Brazilian physical therapists from
the state of Sao Paulo regarding EBP. METHOD: A customized questionnaire about
behavior, knowledge, skills, resources, opinions and perceived barriers regarding
EBP was sent by email to a sample of 490 physical therapists registered by the
Registration Board of Sao Paulo, Brazil. Physical therapists who did not respond
to the questionnaire were contacted by telephone and/or letter. The data were
analyzed descriptively. RESULTS: The final response rate was 64.4% (316/490).
Because 60 physical therapists were no longer practicing, 256 answers were
analyzed. The physical therapists reported that they routinely read scientific
papers (89.5%) as a resource for professional development, followed by continuing
education courses (88.3%) and books (86.3%). Approximately 35% of the respondents
reported a clear understanding of the implementation of research findings in
their practice; approximately 37% reported no difficulties in critically
appraising scientific papers; and 67.2% strongly agreed that EBP is important for
their practice. The most commonly reported barriers were related to difficulties
in obtaining full-text papers (80.1%), using EBP may represent higher cost
(80.1%) and the language of publication of the papers (70.3%). CONCLUSION:
Physical therapists from Sao Paulo state believe that they have knowledge and
skills to use EBP. Although they have favorable opinions regarding its
implementation, they still encounter difficulties in implementing EBP
successfully.
PMID- 26443978
TI - Joint positioning sense, perceived force level and two-point discrimination tests
of young and active elderly adults.
AB - BACKGROUND: Changes in the proprioceptive system are associated with aging.
Proprioception is important to maintaining and/or recovering balance and to
reducing the risk of falls. OBJECTIVE: To compare the performance of young and
active elderly adults in three proprioceptive tests. METHOD: Twenty-one active
elderly participants (66.9 +/- 5.5 years) and 21 healthy young participants (24.6
+/- 3.9 years) were evaluated in the following tests: perception of position of
the ankle and hip joints, perceived force level of the ankle joint, and two-point
discrimination of the sole of the foot. RESULTS: No differences (p>0.05) were
found between groups for the joint position and perceived force level. On the
other hand, the elderly participants showed lower sensitivity in the two-point
discrimination (higher threshold) when compared to the young participants (p <
0.01). CONCLUSION: Except for the cutaneous plantar sensitivity, the active
elderly participants had maintained proprioception. Their physical activity
status may explain similarities between groups for the joint position sense and
perceived force level, however it may not be sufficient to prevent sensory
degeneration with aging.
PMID- 26443979
TI - Moderating effect of the environment in the relationship between mobility and
school participation in children and adolescents with cerebral palsy.
AB - BACKGROUND: The literature demonstrates that the social participation of children
with disabilities is influenced by both their functional skills repertoire and
environmental factors. However, it is not yet known whether the effect of
functional limitations on social participation is minimized or enhanced by the
environmental facilitators and barriers. This study aimed to test this
hypothesis. OBJECTIVE: To investigate the moderating effect of environmental
factors in the relationship between mobility and school participation of children
and adolescents with cerebral palsy (CP). METHOD: Participants were 102
elementary school children and adolescents with CP, aged 6 to 17 years,
classified as levels I, II, and III according to the Gross Motor Classification
System, along with their parents or caregivers and teachers. School participation
and parents' perceptions of barriers were evaluated using the School Function
Assessment and the Craig Hospital Inventory of Environmental Factors (CHIEF),
respectively. RESULTS: The regression model failed to reveal a moderating effect
of environmental factors in the relationship between mobility and school
participation. While mobility was a strong predictor of participation,
environmental factors demonstrated a weak predictive effect on the latter. The
CHIEF subscale school/work showed the factors which were greatest barrier to
children's participation, while the subscale attitude/support had the least
impact. CONCLUSION: The absence of moderation on the tested relationship suggests
that, when investigated under the negative perspective of environmental barriers,
the contextual factors do not modify the relationship between mobility and school
participation. Factors specific to the school environment might add to the
present study's results regarding the effect of school participation in this
population.
PMID- 26443980
TI - Usage evaluation of the Physiotherapy Evidence Database (PEDro) among Brazilian
physical therapists.
AB - BACKGROUND: It is unclear whether the Physiotherapy Evidence Database (PEDro) is
widely and equally used by physical therapists in Brazil. As PEDro is considered
a key resource to support evidence-based physical therapy, analyses of PEDro
usage could reflect the extent of dissemination of evidence-based practice.
OBJECTIVE: To describe the usage of PEDro among the five regions of the World
Confederation for Physical Therapy (WCPT) and, in more detail, in the South
American region and Brazil over a 5-year period. METHOD: PEDro home-page sessions
and the number of searches performed were logged for a 5-year period (2010-2014).
Absolute usage and relative usage were calculated for each region of the WCPT,
each country in the South American region of WCPT, and each Regional Council
(CREFITO) in Brazil. RESULTS: Europe had the highest absolute and relative usage
among the five regions of the WCPT (971 searches per million-population per
year), with the South American region ranked 4th in absolute terms and 3rd in
relative terms (486). Within the South American region, Brazil accounted for
nearly 60% of searches (755). Analysis at a national level revealed that usage
per physical therapist in Brazil is very low across all CREFITOs. The highest
usage occurred in CREFITO 6 with 1.3 searches per physical therapist per year.
CONCLUSIONS: PEDro is not widely and equally used throughout Brazil. Strategies
to promote PEDro and to make PEDro more accessible to physical therapists
speaking Portuguese are needed.
PMID- 26443981
TI - A novel, self-shielded modular radiosynthesis system for fully automated
preparation of PET and therapeutic radiopharmaceuticals.
AB - OBJECTIVE: With the vast development of theranostics and, recently, (68)Ga
radiolabeled molecules, there is also a need for novel, smaller, flexible, safe,
and efficient modular automated synthesis systems in different clinical settings.
The aim of our study was to determine the shielding properties of the modular
self-shielded automated radiosynthesis box and determine its suitability for
routine preparation of different radiopharmaceuticals to be used for diagnosis
and therapy. METHODS: To evaluate shielding properties, shielding factors were
determined using two different radiation sources: (137)Cs and (68)Ga. The dose
rates were measured at critical points at the surface and 1 m distance from the
surface. Three different methods were used to concentrate and purify (68)Ga
generator eluate. Performance of the system was tested by evaluating several
radiolabeling applications using (68)Ga, (177)Lu, and (90)Y. RESULTS: Dose rates
measured at the surface did not exceed 9 MUSv/h for (68)Ga and 20 MUSv/h when
using (137)Cs. On average, dose rates at the surface were reduced for factors of
1665 and 906, respectively. Different DOTA peptides were labeled successfully
with (68)Ga with radiochemical purities more than 94% using three different
radiolabeling methods. (177)Lu-DOTATATE and (90)Y-DOTATATE were synthesized
reproducibly with a radiochemical purity of more than 99% and more than 97%,
respectively. CONCLUSION: A self-shielded radiosynthesis box is a unique solution
for nuclear medicine departments that lack space for installation of standard
automated synthesis systems set in large and heavy dedicated PET synthesis boxes.
Shielding properties are sufficient for safe clinical use for both PET and beta(
) radioisotopes. Because of its modular design and the simple adaptability of
system parameters, the system can be used for the preparation of different
clinically used radiopharmaceuticals and is also useful for research purposes.
PMID- 26443982
TI - Differential Links Between Leisure Activities and Depressive Symptoms in
Unemployed Individuals.
AB - OBJECTIVE: Unemployment has consistently been linked to an elevated risk for
depression. Exercise, specifically leisure-based physical activities, has
received increasing attention as alternative treatment options. However, because
leisure activities are pursued during discretionary time, it is unclear if the
mental health benefits of physical and leisure activities apply during times of
unemployment as well. METHOD: Depressive symptoms and participation in
recreational activities were assessed in 142 employed and 158 unemployed
participants (age = 34 +/- 11 years; male = 150). RESULTS: Independent of
employment status, all recreational activities were inversely associated with
depressive symptoms. However, social (employed: etap (2) = .21; unemployed: etap
(2) = .11) and self-focused (employed: etap (2) = .19; unemployed: etap (2) =
.10) recreational activities were more strongly related to depressive symptoms
than exercise (employed: etap (2) = .12; unemployed: etap (2) > .05). CONCLUSION:
These findings highlight the strong mental health associations of recreational
activities and suggest that, particularly for unemployed individuals, promoting
recreational activities, rather than exercise, may leverage the stronger negative
relationship with risk of depression.
PMID- 26443983
TI - Maternal Mortality versus Researcher's Responsibility to Contribute to Its
Reduction.
PMID- 26443984
TI - The Importance of Null Findings: Preterm Delivery and Cardiovascular Disease.
PMID- 26443985
TI - Air Pollution, Neighbourhood Socioeconomic Factors, and Neural Tube Defects in
the San Joaquin Valley of California.
AB - BACKGROUND: Environmental pollutants and neighbourhood socioeconomic factors have
been associated with neural tube defects, but the potential impact of interaction
between ambient air pollution and neighbourhood socioeconomic factors on the
risks of neural tube defects is not well understood. METHODS: We used data from
the California Center of the National Birth Defects Study and the Children's
Health and Air Pollution Study to investigate whether associations between air
pollutant exposure in early gestation and neural tube defects were modified by
neighbourhood socioeconomic factors in the San Joaquin Valley of California, 1997
2006. There were 5 pollutant exposures, 3 outcomes, and 9 neighbourhood
socioeconomic factors included for a total of 135 investigated associations.
Estimates were adjusted for maternal race-ethnicity, education, and multivitamin
use. RESULTS: We present below odds ratios (ORs) that exclude 1 and a chi-square
test of homogeneity P-value of <0.05. We observed increased odds of spina bifida
comparing the highest to lowest quartile of particulate matter <10 MUm (PM10 )
among those living in a neighbourhood with: (i) median household income of less
than $30 000 per year [OR 5.1, 95% confidence interval (CI) 1.7, 15.3]; (ii) more
than 20% living below the federal poverty level (OR 2.6, 95% CI 1.1, 6.0); and
(iii) more than 30% with less than or equal to a high school education (OR 3.2,
95% CI 1.4, 7.4). The ORs were not statistically significant among those higher
socioeconomic status (SES) neighbourhoods. CONCLUSIONS: Our results demonstrate
effect modification by neighbourhood socioeconomic factors in the association of
particulate matter and neural tube defects in California.
PMID- 26443986
TI - Social Environments, Genetics, and Black-White Disparities in Infant Mortality.
AB - BACKGROUND: Genes and environments often interplay to produce population health.
However, in some instances, the scientific literature has favoured one
explanation, underplaying the other, even in the absence of rigorous support. We
examine parental race disparity on the risk of infant mortality to see if such an
analysis might provide clues to understanding the extent to which genes and
environment may shape perinatal risks. METHODS: We assessed parental racial
disparities in infant mortality among singletons by analysing the risk of infant
mortality among racially consonant vs. dissonant couples over time between 1989
1997 and 1998-2006 in the state of Michigan (n = 1 428 199). We calculated the
degree of modification of the relation between maternal race and infant mortality
by paternal race dynamically across the two time periods. RESULTS: Infant
mortality among interracial couples decreased with time relative to white-white
couples, while infant mortality among black-black couples increased with time
after adjusting for socio-economic, demographic, and prenatal care differences.
The degree to which paternal black race strengthened the relation between
maternal black race and higher infant mortality risk relative to white mothers
increased with time throughout our study. CONCLUSIONS: Evidence from these data
suggests that environmental factors likely play the greater role in explaining
the parental race disparity and risk of infant mortality.
PMID- 26443988
TI - Erratum.
PMID- 26443987
TI - Maternal Recall Error in Retrospectively Reported Time-to-Pregnancy: an
Assessment and Bias Analysis.
AB - BACKGROUND: Epidemiologic studies of fecundability often use retrospectively
measured time-to-pregnancy (TTP), thereby introducing potential for recall error.
Little is known about how recall error affects the bias and precision of the
fecundability odds ratio (FOR) in such studies. METHODS: Using data from the
Danish Snart-Gravid Study (2007-12), we quantified error for TTP recalled in the
first trimester of pregnancy relative to prospectively measured TTP among 421
women who enrolled at the start of their pregnancy attempt and became pregnant
within 12 months. We defined recall error as retrospectively measured TTP minus
prospectively measured TTP. Using linear regression, we assessed mean differences
in recall error by maternal characteristics. We evaluated the resulting bias in
the FOR and 95% confidence interval (CI) using simulation analyses that compared
corrected and uncorrected retrospectively measured TTP values. RESULTS: Recall
error (mean = -0.11 months, 95% CI -0.25, 0.04) was not appreciably associated
with maternal age, gravidity, or recent oral contraceptive use. Women with TTP >
2 months were more likely to underestimate their TTP than women with TTP <= 2
months (unadjusted mean difference in error: -0.40 months, 95% CI -0.71, -0.09).
FORs of recent oral contraceptive use calculated from prospectively measured,
retrospectively measured, and corrected TTPs were 0.82 (95% CI 0.67, 0.99), 0.74
(95% CI 0.61, 0.90), and 0.77 (95% CI 0.62, 0.96), respectively. CONCLUSIONS:
Recall error was small on average among pregnancy planners who became pregnant
within 12 months. Recall error biased the FOR of recent oral contraceptive use
away from the null by 10%. Quantitative bias analysis of the FOR can help
researchers quantify the bias from recall error.
PMID- 26443989
TI - The Association Between Obstructive Sleep Apnea and Nonarteritic Anterior
Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis.
AB - PURPOSE: Nonarteritic anterior ischemic optic neuropathy (NAION) is a
multifactorial disease, and recently epidemiologic studies have investigated the
association between obstructive sleep apnea (OSA) and NAION. A systematic review
of the association of OSA and NAION has not been performed. Therefore, the
current meta-analysis was performed to assess such potential association between
OSA and risk of NAION. METHODS: A systematic search of PubMed and EMBASE
databases was performed for published studies evaluating the association between
OSA and NAION. The summary odds ratios (ORs) and 95% confidence intervals (CIs)
were calculated for categorical risk estimates. Sensitivity analyses and subgroup
analyses were also performed to assess the robustness of pooled outcomes.
RESULTS: A total of four prospective cohort studies and one case-control study
met our inclusion criteria. The pooled OR of developing NAION in the subjects
with OSA was 6.18 (95% CI, 2.00-19.11) versus non-OSA controls. Sensitivity
analyses showed that no matter one study excluded, the pooled OR did not change
significantly, which indicated that the evidence was robust. In subgroup
analyses, a significant association was seen in studies matched systemic risk
factors (OR, 5.00; 95% CI, 2.22-11.25), but not in those non-matched. The
magnitude and direction of effects were also affected by methodological
variability, including study design, and diagnosis of OSA. CONCLUSIONS: The
findings from this meta-analysis supported the robust evidence that OSA was a
strong independent risk factor of NAION. Relative to non-OSA controls, the
subjects with OSA were found to have a more than sixfold risk of NAION. In
future, more well-designed studies are needed to confirm these findings.
PMID- 26443991
TI - Prediction of hyperdynamic circulation by arterial diastolic reflected waveform
analysis in patients undergoing liver transplantation.
AB - OBJECTIVES: In cirrhotic patients with hyperdynamic circulation characterized by
a decrease in systemic vascular resistance (SVR) and an increase in cardiac
output, cardiac and vascular properties are expressed in peripheral arterial
pressure waveforms. We attempted to assess whether the variables derived from the
radial artery waveform can predict hyperdynamic circulation in liver transplant
recipients. MATERIALS AND METHODS: Before surgical incision, we obtained the
simultaneous cardiac index (CI) and SVR determined by a pulmonary artery catheter
in 30 liver transplant recipients. We analyzed the diastolic reflected waveform
characteristics by calculating the diastolic augmentation index (DAIx, %), which
was defined as 100*[peak pressure of diastolic reflected wave-diastolic arterial
pressure]/pulse pressure. The time from diastolic arterial pressure to the peak
of the diastolic reflected wave, corrected by RR intervals (tDA), was also
determined. RESULTS: CI and SVR were correlated with DAIx (r=-0.553, P=0.002 and
r=0.617, P<0.001) and tDA (r=0.504, P=0.004 and r=-0.692, P<0.001). The areas
under the receiver operating characteristic curves were 0.900 [95% confidence
interval: 0.713-0.978 for both DAIx and tDA to predict hyperdynamic circulation
(CI>4.0 l/min/m and SVR<800 dynes.s/cm, n=13)]. DAIx less than 35% and tDA more
than 484 ms were the best cutoff values for differentiation of hyperdynamic
circulation (sensitivity/specificity 92.3%/76.5% and 100%/70.6%, respectively).
CONCLUSION: Diastolic reflected waveform characteristics can be used to predict
high CI and low SVR in liver transplant recipients. This study suggests that
these minimally invasive indicators may also be valuable when pulmonary artery
catheterization is not available in patients with a hyperdynamic condition.
PMID- 26443990
TI - Fully automatic analysis of the knee articular cartilage T1rho relaxation time
using voxel-based relaxometry.
AB - PURPOSE: To develop and compare with the classical region of interest (ROI)-based
approach a fully automatic, local, and unbiased way of studying the knee T1rho
relaxation time by creating an atlas and using voxel-based relaxometry (VBR) in
osteoarthritis (OA) and anterior cruciate ligament (ACL) subjects. MATERIALS AND
METHODS: In this study 110 subjects from two cohorts: 1) Mild OA 40 patients with
mild-OA Kellgren-Lawrence (KL) <= 2 and 15 controls KL <= 1; 2) ACL cohort (a
model for early OA): 40 ACL-injured patients imaged prior to ACL reconstruction
and 1-year postsurgery and 15 controls are analyzed. All the subjects were
acquired at 3T with a protocol that includes: 3D-FSE (CUBE) and 3D-T1rho . A
nonrigid registration technique was applied to align all the images on a single
template. This allows for performing VBR to assess local statistical differences
of T1rho values using z-score analysis. VBR results were compared with those
obtained with classical ROI-based technique. RESULTS: ROI-based results from
atlas-based segmentation were consistent with classical ROI-based method
(coefficient of variation [CV] = 3.83%). Voxel-based group analysis revealed
local patterns that were overlooked by the ROI-based approach; eg, VBR showed
posterior lateral femur and posterior lateral tibia significant T1rho elevations
in ACL-injured patients (sample mean z-score=9.7 and 10.3). Those elevations were
overlooked by the classical ROI-based approach (sample mean z-score=1.87 and
1.73) CONCLUSION: VBR is a feasible and accurate tool for the local evaluation of
the biochemical composition of knee articular cartilage. VBR is capable of
detecting specific local patterns on T1rho maps in OA and ACL subjects.
PMID- 26443992
TI - Super enhanced permeability and retention (SUPR) effects in tumors following near
infrared photoimmunotherapy.
AB - To date, the delivery of nano-sized therapeutic agents to cancers largely relies
on enhanced permeability and retention (EPR) effects that are caused by the leaky
nature of cancer vasculature. However, nano-sized agents delivered in this way
have demonstrated limited success in oncology due to the relatively small
magnitude of the EPR effect. For achieving superior delivery of nano-sized
agents, super-enhanced permeability and retention (SUPR) effects are needed. Near
infrared photo-immunotherapy (NIR-PIT) is a recently reported therapy that treats
tumors with light therapy and subsequently causes an increase in nano-drug
delivery up to 24-fold compared with untreated tumors in which only the EPR
effect is present. SUPR effects could enhance delivery into tumor beds of a wide
variety of nano-sized agents including particles, antibodies, and protein binding
small molecular agents. Therefore, taking advantage of the SUPR effects after NIR
PIT may be a promising avenue to utilize a wide variety of nano-drugs in a highly
effective manner.
PMID- 26443993
TI - Frequency of cancer events with saxagliptin in the SAVOR-TIMI 53 trial.
AB - The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with
Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial
randomized trial of 16,492 patients (placebo, n = 8212; saxagliptin, n = 8280)
treated and followed for a median of 2.1 years afforded an opportunity to explore
whether there was any association with cancer reported as a serious adverse
event. At least one cancer event was reported by 688 patients (4.1%): 362 (4.3%)
and 326 (3.8%) in the placebo and saxagliptin arms, respectively (p = 0.13).
There were 59 (0.6%) deaths adjudicated as malignancy deaths with placebo and 53
(0.6%) with saxagliptin. Stratification by gender, age, race and ethnicity,
diabetes duration, baseline glycated haemoglobin and pharmacotherapy did not show
any clinically meaningful differences between the two study arms. The overall
number of cancer events and malignancy-associated mortality rates were generally
balanced between the placebo and saxagliptin groups, suggesting a null
relationship with saxagliptin use over the median follow-up of 2.1 years.
Multivariable modelling showed that male gender, dyslipidaemia and current
smoking were independent predictors of cancer. These randomized data with
adequate numbers of cancer cases are reassuring but limited, by the short follow
up in a trial not designed to test this hypothesis.
PMID- 26443995
TI - High-Intensity Induction Chemotherapy Is Feasible for Elderly Patients with Acute
Myeloid Leukemia.
AB - BACKGROUND: The prognosis of elderly patients with acute myeloid leukemia (AML)
is poor, and the best treatment is controversial. Since the majority of AML
patients are older than 60 years, identification of those who might benefit from
intensive treatment is essential. METHODS: Data from electronic charts of
consecutive AML patients treated in our center were analyzed. Eligibility
criteria included newly diagnosed de novo or secondary AML, an age of 60 years or
older, and intensive induction treatment. RESULTS: Sixty-two patients were
included in the analysis. Forty-six patients (74%) achieved complete remission
(CR) after 1-2 intensive induction courses. Twenty of them received consolidation
with conventional chemotherapy, 20 proceeded to allogeneic hematopoietic cell
transplantation (allo-HCT), and 6 were ineligible for further treatment. The
projected overall survival (OS) at 2 and 3 years was 28 and 23%, respectively. A
normal karyotype, CR achievement, and allo-HCT were associated with improved OS,
while an Eastern Cooperative Oncology Group performance status of 0-1 was
borderline associated. The median survival and disease-free survival at 2 years
was 18.7 months and 49%, respectively, for patients who underwent allo-HCT in
CR1, compared to 12.8 months and 25%, respectively, for those who did not.
CONCLUSION: Based on our data, selected eligible elderly AML patients might
benefit from intensive treatment.
PMID- 26443994
TI - Cooperative and independent functions of FGF and Wnt signaling during early inner
ear development.
AB - BACKGROUND: In multiple vertebrate organisms, including chick, Xenopus, and
zebrafish, Fibroblast Growth Factor (FGF) and Wnt signaling cooperate during
formation of the otic placode. However, in the mouse, although FGF signaling
induces Wnt8a expression during induction of the otic placode, it is unclear
whether these two signaling pathways functionally cooperate. Sprouty (Spry) genes
encode intracellular antagonists of receptor tyrosine kinase signaling, including
FGF signaling. We previously demonstrated that the Sprouty1 (Spry1) and Sprouty2
(Spry2) genes antagonize FGF signaling during induction of the otic placode.
Here, we investigate cross talk between FGF/SPRY and Wnt signaling during otic
placode induction and assess whether these two signaling pathways functionally
cooperate during early inner ear development in the mouse. METHODS: Embryos were
generated carrying combinations of a Spry1 null allele, Spry2 null allele, beta
catenin null allele, or a Wnt reporter transgene. Otic phenotypes were assessed
by in situ hybridization, semi-quantitative reverse transcriptase PCR,
immunohistochemistry, and morphometric analysis of sectioned tissue. RESULTS:
Comparison of Spry1, Spry2, and Wnt reporter expression in pre-otic and otic
placode cells indicates that FGF signaling precedes and is active in more cells
than Wnt signaling. We provide in vivo evidence that FGF signaling activates the
Wnt signaling pathway upstream of TCF/Lef transcriptional activation. FGF
regulation of Wnt signaling is functional, since early inner ear defects in Spry1
and Spry2 compound mutant embryos can be genetically rescued by reducing the
activity of the Wnt signaling pathway. Interestingly, we find that although the
entire otic placode increases in size in Spry1 and Spry2 compound mutant embryos,
the size of the Wnt-reporter-positive domain does not increase to the same extent
as the Wnt-reporter-negative domain. CONCLUSIONS: This study provides genetic
evidence that FGF and Wnt signaling cooperate during early inner ear development
in the mouse. Furthermore, our data suggest that although specification of the
otic placode may be globally regulated by FGF signaling, otic specification of
cells in which both FGF and Wnt signaling are active may be more tightly
regulated.
PMID- 26443996
TI - Influence of supplemental parenteral nutrition approach on nosocomial infection
in pediatric intensive care unit of Emergency Department: a retrospective study.
AB - BACKGROUND & AIMS: Nutritional support for patients in the intensive-care unit
(ICU) is a part of standard care which promotes medical quality and decreases
nosocomial infection. Supplemental parenteral nutrition (SPN) approach (enteral
nutrition (EN) combined with parenteral nutrition (PN) when EN alone is
insufficient) has become one major concern in nutrition research field. This
research aims to explore the following relationships: (i) the relationship
between SPN and nosocomial infection, (ii) the relationship between early and
late SPN initiation and the development of nosocomial infection. METHODS: A
retrospective study was conducted in patients who met the inclusion criteria from
February 2012 to February 2015 in Pediatric ICU (PICU). Patients were classified
into two groups according to nutrition delivery approach-SPN group and EN alone
group. Then SPN group were further divided into two subgroups by initiation
timing, which were defined as early-initiation SPN and late-initiation SPN group
respectively. Age, gender, serum albumin at admission, severity of disease,
length of stay in PICU, nutrition delivery approach, amounts of delivered caloric
intake and occurence of nosocomial infection were recorded. Univariate analysis
and binary logistic regression analysis were performed to identify the risk
factors and assess the independent effect of SPN approach on nosocomial infection
in PICU of Emergency Department. RESULTS: 204 patients were included in our
study. Compared with EN alone group, patients delivered by SPN approach had a
higher nosocomial infection rate (34.0 vs.10.9%, p < 0.001). The late-initiation
subgroup of SPN approach was found to be an independent predictor of nosocomial
infection in the logistic regression analysis model (OR = 3.40; 95% CI, 1.13 ~
10.19; p = 0.029). Serum albumin at admission (OR = 0.91; 95% CI, 0.84 ~ 0.97; p
= 0.008), mechanical ventilation (OR = 3.85; 95% CI, 1.43 ~ 10.39; p = 0.008),
severity of disease (OR = 3.79; 95% CI, 1.03 ~ 13.99; p = 0.045) and PICU length
of stay (OR = 1.23; 95% CI, 1.11 ~ 1.35; p < 0.001) were also identified as
significant risk factors for nosocomial infection. CONCLUSIONS: Our study shows
late-initiation SPN approach increases the incidence of nosocomial infection
compared with early-initiation approach in critically ill children in PICU of
Emergency Department. Compared with EN alone group, patients delivered by SPN
approach had a higher nosocomial infection rate.
PMID- 26443997
TI - Effects of melatonin on the nitric oxide system and protein nitration in the
hypobaric hypoxic rat hippocampus.
AB - BACKGROUND: It is well documented that the nitric oxide (NO) might be directly
involved in brain response to hypobaric hypoxia, and could contribute to memory
deficiencies. Recent studies have shown that melatonin could attenuate hypoxia or
ischemia-induced nerve injuries by decreasing the production of free radicals.
The present study, using immunohistochemical and immunoblot methods, aimed to
explore whether melatonin treatment may affect the expression of nitric oxide
system and protein nitration, and provide neuroprotection in the rat hippocampus
injured by hypobaric hypoxia. Prior to hypoxic treatment, adult rats were
pretreated with melatonin (100 mg/kg, i.p.) before they were exposed to the
altitude chamber with 48 Torr of the partial oxygen concentration (pO2) for 7 h
to mimic the ambience of being at 9000 m in height. They were then sacrificed
after 0 h, 1, and 3 days of reoxygenation. RESULTS: The results obtained from the
immunohistochemical and immunoblotting analyses showed that the expressions of
neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS),
inducible nitric oxide synthase (iNOS), nitrotyrosine (Ntyr) and Caspase 3 in the
hypoxic hippocampus were increased from 0 h to 3 days of reoxygenation.
Interestingly, the hypoxia-induced increase of nNOS, eNOS, iNOS, Ntyr and Caspase
3 protein expression was significantly depressed in the hypoxic rats treated with
melatonin. CONCLUSIONS: Activation of the nitric oxide system and protein
nitration constitutes a hippocampal response to hypobaric hypoxia and
administration of melatonin could provide new therapeutic avenues to prevent
and/or treat the symptoms produced by hypobaric hypoxia.
PMID- 26443998
TI - Predicting Falls in Parkinson Disease: What Is the Value of Instrumented Testing
in OFF Medication State?
AB - BACKGROUND: Falls are a common complication of advancing Parkinson's disease
(PD). Although numerous risk factors are known, reliable predictors of future
falls are still lacking. The objective of this prospective study was to
investigate clinical and instrumented tests of balance and gait in both OFF and
ON medication states and to verify their utility in the prediction of future
falls in PD patients. METHODS: Forty-five patients with idiopathic PD were
examined in defined OFF and ON medication states within one examination day
including PD-specific clinical tests, instrumented Timed Up and Go test (iTUG)
and computerized dynamic posturography. The same gait and balance tests were
performed in 22 control subjects of comparable age and sex. Participants were
then followed-up for 6 months using monthly fall diaries and phone calls.
RESULTS: During the follow-up period, 27/45 PD patients and 4/22 control subjects
fell one or more times. Previous falls, fear of falling, more severe motor
impairment in the OFF state, higher PD stage, more pronounced depressive
symptoms, higher daily levodopa dose and stride time variability in the OFF state
were significant risk factors for future falls in PD patients. Increased stride
time variability in the OFF state in combination with faster walking cadence
appears to be the most significant predictor of future falls, superior to
clinical predictors. CONCLUSION: Incorporating instrumented gait measures into
the baseline assessment battery as well as accounting for both OFF and ON
medication states might improve future fall prediction in PD patients. However,
instrumented testing in the OFF state is not routinely performed in clinical
practice and has not been used in the development of fall prevention programs in
PD. New assessment methods for daylong monitoring of gait, balance and falls are
thus required to more effectively address the risk of falling in PD patients.
PMID- 26443999
TI - Why (we think) facilitation works: insights from organizational learning theory.
AB - BACKGROUND: Facilitation is a guided interactional process that has been
popularized in health care. Its popularity arises from its potential to support
uptake and application of scientific knowledge that stands to improve clinical
and managerial decision-making, practice, and ultimately patient outcomes and
organizational performance. While this popular concept has garnered attention in
health services research, we know that both the content of facilitation and its
impact on knowledge implementation vary. The basis of this variation is poorly
understood, and understanding is hampered by a lack of conceptual clarity.
DISCUSSION: In this paper, we argue that our understanding of facilitation and
its effects is limited in part by a lack of clear theoretical grounding. We
propose a theoretical home for facilitation in organizational learning theory.
Referring to extant literature on facilitation and drawing on theoretical
literature, we discuss the features of facilitation that suggest its role in
contributing to learning capacity. We describe how facilitation may contribute to
generating knowledge about the application of new scientific knowledge in health
care organizations. Facilitation's promise, we suggest, lies in its potential to
stimulate higher-order learning in organizations through experimenting with,
generating learning about, and sustaining small-scale adaptations to
organizational processes and work routines. The varied effectiveness of
facilitation observed in the literature is associated with the presence or
absence of factors known to influence organizational learning, since facilitation
itself appears to act as a learning mechanism. We offer propositions regarding
the relationships between facilitation processes and key organizational learning
concepts that have the potential to guide future work to further our
understanding of the role that facilitation plays in learning and knowledge
generation.
PMID- 26444000
TI - Heightened Delta Power during Slow-Wave-Sleep in Patients with Rett Syndrome
Associated with Poor Sleep Efficiency.
AB - Sleep problems are commonly reported in Rett syndrome (RTT); however the
electroencephalographic (EEG) biomarkers underlying sleep dysfunction are poorly
understood. The aim of this study was to analyze the temporal evolution of
quantitative EEG (qEEG) biomarkers in overnight EEGs recorded from girls (2-9
yrs. old) diagnosed with RTT using a non-traditional automated protocol. In this
study, EEG spectral analysis identified high delta power cycles representing slow
wave sleep (SWS) in 8-9h overnight sleep EEGs from the frontal, central and
occipital leads (AP axis), comparing age-matched girls with and without RTT.
Automated algorithms quantitated the area under the curve (AUC) within identified
SWS cycles for each spectral frequency wave form. Both age-matched RTT and
control EEGs showed similar increasing trends for recorded delta wave power in
the EEG leads along the antero-posterior (AP). RTT EEGs had significantly fewer
numbers of SWS sleep cycles; therefore, the overall time spent in SWS was also
significantly lower in RTT. In contrast, the AUC for delta power within each SWS
cycle was significantly heightened in RTT and remained heightened over
consecutive cycles unlike control EEGs that showed an overnight decrement of
delta power in consecutive cycles. Gamma wave power associated with these SWS
cycles was similar to controls. However, the negative correlation of gamma power
with age (r = -.59; p<0.01) detected in controls (2-5 yrs. vs. 6-9 yrs.) was lost
in RTT. Poor % SWS (i.e., time spent in SWS overnight) in RTT was also driven by
the younger age-group. Incidence of seizures in RTT was associated with
significantly lower number of SWS cycles. Therefore, qEEG biomarkers of SWS in
RTT evolved temporally and correlated significantly with clinical severity.
PMID- 26444002
TI - Sporangium Exposure and Spore Release in the Peruvian Maidenhair Fern (Adiantum
peruvianum, Pteridaceae).
AB - We investigated the different processes involved in spore liberation in the
polypod fern Adiantum peruvianum (Pteridaceae). Sporangia are being produced on
the undersides of so-called false indusia, which are situated at the abaxial
surface of the pinnule margins, and become exposed by a desiccation-induced
movement of these pinnule flaps. The complex folding kinematics and functional
morphology of false indusia are being described, and we discuss scenarios of
movement initiation and passive hydraulic actuation of these structures. High
speed cinematography allowed for analyses of fast sporangium motion and for
tracking ejected spores. Separation and liberation of spores from the sporangia
are induced by relaxation of the annulus (the 'throwing arm' of the sporangium
catapult) and conservation of momentum generated during this process, which leads
to sporangium bouncing. The ultra-lightweight spores travel through air with a
maximum velocity of ~5 m s(-1), and a launch acceleration of ~6300 g is measured.
In some cases, the whole sporangium, or parts of it, together with contained
spores break away from the false indusium and are shed as a whole. Also, spores
can stick together and form spore clumps. Both findings are discussed in the
context of wind dispersal.
PMID- 26444001
TI - Use of and short-term impacts of new cycling infrastructure in inner-Sydney,
Australia: a quasi-experimental design.
AB - BACKGROUND: Given increasing investment in new cycling infrastructure, it is
important to understand its impacts. The Sydney Transport and Health Study
evaluates a new 2.4 km bi-directional separated bicycle path in inner-Sydney.
This paper describes the users of the new bicycle path, and examines its short
term impacts upon cycling behaviour and perceptions of the local environment.
METHODS: Data were collected from two bike counts at two intersections on the new
bicycle path in the intervention area in 2013 and 2014. On-line surveys collected
individual participant data in the intervention area and a similar comparison
area before the bicycle path was built (2013), and 12 months later (four months
after completion) (n = 512). The data included self-reported cycling behaviour,
use of the new bicycle path and perceptions of changes in the local environment.
RESULTS: Bike counts at two sites on the new bicycle path reported an increase of
23% and 97% respectively at 12 months. However, among the participants in the
cohort, there was no change in the self-reported weekly frequency of cycling. One
in six (approximately 15%) participants reported using the new bicycle path, with
most users (76%) living in the intervention area. Bicycle path users were most
likely to be frequent riders (at least weekly) [adjusted odds ratio (AOR) = 7.50,
95 % CI 3.93-14.31], be a high intensity recreational rider (AOR = 4.38, 95 % CI
1.53-12.54) or a low intensity transport rider (AOR = 2.42, 95 % CI 1.17-5.04)
and live closer to the bicycle path (AOR = 1.24, 1.13-1.37). Perceptions that the
neighbourhood was more pleasant, that there were more people walking and cycling
were significantly higher in the intervention area at 12 months (both P values
<0.05). CONCLUSIONS: Existing cycling behaviour and proximity to the bicycle path
were associated with the use of the new bicycle path. Increased use of the new
bicycle path as reported by the participants in the intervention area and
increased cycling recorded by the bike counts may be due to existing cyclists
changing routes to use the new path, and more cyclists from outside the study
area using the new path, as study participants did not increase their frequency
of cycling. Increases in cycling frequency in the intervention neighbourhood may
require a longer lead time, additional promotional activities and further
maturation of the Sydney bicycle path network. KEY MESSAGE: Understanding how new
cycling infrastructure impacts communities can influence the promotion of such
infrastructure.
PMID- 26444003
TI - Hemodialysis versus Peritoneal Dialysis: A Comparison of Survival Outcomes in
South-East Asian Patients with End-Stage Renal Disease.
AB - BACKGROUND: Studies comparing patient survival of hemodialysis (HD) and
peritoneal dialysis (PD) have yielded conflicting results and no such study was
from South-East Asia. This study aimed to compare the survival outcomes of
patients with end-stage renal disease (ESRD) who started dialysis with HD and PD
in Singapore. METHODS: Survival data for a maximum of 5 years from a single
center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n =
230) from 2005-2010 was analyzed using the flexible Royston-Parmar (RP) model.
The model was also applied to a subsample of 225 propensity-score-matched patient
pairs and subgroups defined by age, diabetes mellitus, and cardiovascular
disease. RESULTS: After adjusting for the effect of socio-demographic and
clinical characteristics, the risk of death was higher in patients initiating
dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08;
95% confidence interval [CI]: 1.67-2.59; p<0.001), although there was no
significant difference in mortality between the two modalities in the first 12
months of treatment. Consistently, in the matched subsample, patients starting PD
had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30-2.28,
p<0.001). Subgroup analysis showed that PD may be similar to or better than HD in
survival outcomes among young patients (<=65 years old) without diabetes or
cardiovascular disease. CONCLUSION: ESRD patients who initiated dialysis with HD
experienced better survival outcomes than those who initiated dialysis with PD in
Singapore, although survival outcomes may not differ between the two dialysis
modalities in young and healthier patients. These findings are potentially
confounded by selection bias, as patients were not randomized to the two dialysis
modalities in this cohort study.
PMID- 26444004
TI - Steroid Treatment Reduces Allergic Airway Inflammation and Does Not Alter the
Increased Numbers of Dendritic Cells and Calcitonin Gene-Related Peptide
Expressing Neurons in Airway Sensory Ganglia.
AB - OBJECTIVES: Our previous data demonstrated that allergic airway inflammation
induces migration of dendritic cells (DC) into airway sensory jugular and nodose
ganglia (jugular-nodose ganglion complex; JNC). Here we investigated the effects
of steroid treatment regarding the expression and migration of DC and calcitonin
gene-related peptide (CGRP)-immunoreactive neurons of vagal sensory ganglia
during allergic airway inflammation. METHODS: A house dust mite (HDM) model for
allergic airway inflammation was used. The mice received 0.3 mg fluticasone
propionate per kilogram of body weight in the last 9 days. JNC slices were
analyzed on MHC II, the neuronal marker PGP9.5, and the neuropeptide CGRP.
RESULTS: Allergic airway inflammation increased the numbers of DC and CGRP
expressing neurons in the JNC significantly in comparison to the controls
(DC/neurons: HDM 44.58 +/- 1.6% vs. saline 33.29 +/- 1.6%, p < 0.05; CGRP
positive neurons/total neurons: HDM 30.65 +/- 1.9% vs. saline 19.49 +/- 2.3%, p <
0.05). Steroid treatment did not have any effect on the numbers of DC and CGRP
expressing neurons in the JNC compared to HDM-treated mice. CONCLUSIONS: The
present findings indicate an important role of DC and CGRP-containing neurons in
the pathogenesis of allergic airway inflammation. However, steroid treatment did
not have an effect on the population of DC and neurons displaying CGRP in the
JNC, whereas steroid treatment was found to suppress allergic airway
inflammation.
PMID- 26444005
TI - Functional characterization of biodegradable nanoparticles as antigen delivery
system.
AB - BACKGROUND: Peptide based vaccines may suffer from limited stability and
inefficient delivery to professional antigen-presenting cells (APCs), such as
dendritic cells (DCs). In order to overcome such limitations, several types of
biodegradable nanoparticles (NPs) have been developed as carrier system for
antigens. The present study describes for the first time the extensive biological
characterization of cationic NPs made of poly (D,L-lactide-co-glycolide) (PLGA)
and polyethylenimine (PLGA/PEI) as delivery system for protein/peptide antigens,
with potential in therapeutic cancer vaccine development. RESULTS: Flow cytometry
as well as confocal laser scanning microscopy (CLSM) showed that PLGA/PEI NPs are
more readily taken up than PLGA NPs by both human CD14(+) monocytes and mouse
Hepa 1-6 hepatoma cell line. No signs of toxicity were observed in either
cellular setting. Sequential image acquisition by TEM showed an intracellular
apical localization for PLGA NPs and a perinuclear localization for PLGA/PEI NPs.
Both NPs showed a clathrin-dependent as well as a caveolin-dependent
internalization pathway and, once in the cells, they formed multivesicular
endosomes (MVE). Finally, an ex vivo priming experiment showed that PLGA/PEI NPs
are comparable to PLGA NPs in delivering a non-self antigen (i.e., ovalbumin -
OVA) to immature dendritic cells (imDCs), which matured and induced autologous
naive CD4(+) T cells to differentiate to memory (i.e., central memory and
effector memory) cells. Such a differentiation was associated with a Th1
phenotype suggesting a downstream activation and amplification of a CD8(+) T cell
cytotoxic response. The same OVA antigen in a soluble form was unable to induce
maturation of DCs, indicating that both NP formulations provided an intrinsic
adjuvanting effect combined to efficient antigen delivery. CONCLUSIONS: Our study
represents the first report on side-by-side comparison of PLGA and PLGA/PEI NPs
as strategy for protein antigen delivery. PLGA/PEI NPs are superior for cellular
uptake and antigen delivery as compared to PLGA NPs. Such an evidence suggests
their great potential value for vaccine development, including therapeutic cancer
vaccines.
PMID- 26444006
TI - Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.
AB - INTRODUCTION: Preeclampsia is a maternal hypertensive disorder with uncertain
etiology and a leading cause of maternal and fetal mortality worldwide, causing
nearly 40% of premature births delivered before 35 weeks of gestation. The first
stage of preeclampsia is characterized by reduction of utero-placental blood flow
which is reflected in high blood pressure and proteinuria during the second half
of pregnancy. In human placenta androgens derived from the maternal and fetal
adrenal glands are converted into estrogens by the enzymatic action of placental
aromatase. This implies that alterations in placental steroidogenesis and,
subsequently, in the functionality or bioavailability of placental aromatase may
be mechanistically involved in the pathophysiology of PE. METHODS: Serum samples
were collected at 32-36 weeks of gestation and placenta biopsies were collected
at time of delivery from PE patients (n = 16) and pregnant controls (n = 32). The
effect of oxygen tension on placental cells was assessed by incubation JEG-3
cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New
Zealand white rabbits (n = 6) were used to establish an in vivo model of
placental ischemia (achieved by ligature of uteroplacental vessels). Aromatase
content and estrogens and androgens concentrations were measured. RESULTS: The
protein and mRNA content of placental aromatase significantly diminished in
placentae obtained from preeclamptic patients compared to controls. Similarly,
the circulating concentrations of 17-beta-estradiol/testosterone and
estrone/androstenedione were reduced in preeclamptic patients vs. controls. These
data are consistent with a concomitant decrease in aromatase activity. Aromatase
content was reduced in response to low oxygen tension in the choriocarcinoma JEG
3 cell line and in rabbit placentae in response to partial ligation of uterine
spiral arteries, suggesting that reduced placental aromatase activity in
preeclamptic patients may be associated with chronic placental ischemia and
hypoxia later in gestation. CONCLUSIONS: Placental aromatase expression and
functionality are diminished in pregnancies complicated by preeclampsia in
comparison with healthy pregnant controls.
PMID- 26444007
TI - Synchronous mucosal Schwann-cell hamartomas in a young adult suggestive of
mucosal Schwann-cell harmatomatosis: a case report.
AB - BACKGROUND: Mucosal Schwann-cell hamartoma is a rare mesenchymal polyp that
presents in the intestine. Despite lacking ganglion cells, it resembles a
gastrointestinal ganglioneuroma. CASE PRESENTATION: We report a case of
synchronous mucosal Schwann-cell hamartomas in a young male patient, who
presented with a single discrete polyp in the mid-rectum and multiple polypoid
mucosal lesions in the distal rectum. CONCLUSION: To the best of our knowledge,
this is the first report of a case of multiple mucosal Schwann-cell hamartomas.
PMID- 26444008
TI - CD24 Overexpression Is Associated with Poor Prognosis in Luminal A and Triple
Negative Breast Cancer.
AB - CD24 is associated with unfavourable prognoses in various cancers, but the
prevalence of CD24 expression and its influence on clinical outcome in subtypes
of breast cancers remain unclear. CD24 expression was analyzed by
immunohistochemistry in 747 breast cancer tissues, and DNA methylation and
histone modification status in the promoter region of CD24 were assessed using
bisulfite sequencing and chromatin immunoprecipitation assay. 213 (28.5%) samples
exhibited high CD24 expression in the membrane and/or cytoplasm of breast cancer
cells, and CD24 overexpression was significantly correlated with the presence of
lymph node metastasis and more advanced pathological stage. Patients with CD24
high tumours had significantly shorter patient survival than those with CD24-low
tumours. Importantly, multivariate analysis that included tumour size, lymph node
metastasis and chemotherapy demonstrated that high CD24 expression is
independently associated with poorer survival in luminal A and triple-negative
breast cancer (TNBC) subtypes. Furthermore, CD24 gene expression was associated
with histone acetylation independent of DNA methylation, suggesting its
epigenetic regulation in breast cancer. Our results suggest that CD24
overexpression is an independent unfavourable prognostic factor in breast cancer,
especially for luminal A and TNBC subtypes, and CD24 may be a promising
therapeutic target for specific subtypes of breast cancer.
PMID- 26444009
TI - Boundaries and conditions of interpretation in multilingual and multicultural
elderly healthcare.
AB - BACKGROUND: Elderly migrants who do not speak the official language of their host
country have increased due to extensive international migration, and will further
increase in the future. This entails major challenges to ensure good
communication and avoid communication barriers that can be overcome by the use of
adequate interpreter services. To our knowledge, there are no previous
investigations on interpreting practices in multilingual elderly healthcare from
different healthcare professionals' perspectives. This study examines issues
concerning communication and healthcare through a particular focus on
interpretation between health professionals and patients of different ethnic and
linguistic backgrounds. The central aim of the project is to explore
interpretation practices in multilingual elderly healthcare. METHODS: A purposive
sample of 33 healthcare professionals with experience of using interpreters in
community multilingual elderly healthcare. Data were collected between October
2013 and March 2014 by 18 individual and four focus group interviews and analysed
with qualitative content analysis. RESULTS: The main results showed that
interpreting practice in multilingual elderly healthcare was closely linked to
institutional, interpersonal and individual levels. On the organizational level,
however, guidelines for arranging the use of interpreters at workplaces were
lacking. Professional interpreters were used on predictable occasions planned
long in advance, and bilingual healthcare staff and family members acting as
interpreters were used at short notice in everyday caring situations on
unpredictable occasions. The professional interpreter was perceived as a person
who should interpret spoken language word-for-word and who should translate
written information. Furthermore, the use of a professional interpreter was not
adapted to the context of multilingual elderly healthcare. CONCLUSION: This study
found that interpreter practice in multilingual elderly healthcare is embedded in
the organizational environment and closely related to the individual's language
skills, cultural beliefs and socio-economic factors. In order to formulate
interpreter practice in the context of multilingual elderly healthcare it is
important to consider organizational framework and cultural competence, cultural
health knowledge, beliefs and customs.
PMID- 26444010
TI - Seeing More by Showing Less: Orientation-Dependent Transparency Rendering for
Fiber Tractography Visualization.
AB - Fiber tractography plays an important role in exploring the architectural
organization of fiber trajectories, both in fundamental neuroscience and in
clinical applications. With the advent of diffusion MRI (dMRI) approaches that
can also model "crossing fibers", the complexity of the fiber network as
reconstructed with tractography has increased tremendously. Many pathways
interdigitate and overlap, which hampers an unequivocal 3D visualization of the
network and impedes an efficient study of its organization. We propose a novel
fiber tractography visualization approach that interactively and selectively
adapts the transparency rendering of fiber trajectories as a function of their
orientation to enhance the visibility of the spatial context. More specifically,
pathways that are oriented (locally or globally) along a user-specified opacity
axis can be made more transparent or opaque. This substantially improves the 3D
visualization of the fiber network and the exploration of tissue configurations
that would otherwise be largely covered by other pathways. We present examples of
fiber bundle extraction and neurosurgical planning cases where the added benefit
of our new visualization scheme is demonstrated over conventional fiber
visualization approaches.
PMID- 26444011
TI - Sex Differences in Object Manipulation in Wild Immature Chimpanzees (Pan
troglodytes schweinfurthii) and Bonobos (Pan paniscus): Preparation for Tool Use?
AB - Sex differences in immatures predict behavioural differences in adulthood in many
mammal species. Because most studies have focused on sex differences in social
interactions, little is known about possible sex differences in 'preparation' for
adult life with regards to tool use skills. We investigated sex and age
differences in object manipulation in immature apes. Chimpanzees use a variety of
tools across numerous contexts, whereas bonobos use few tools and none in
foraging. In both species, a female bias in adult tool use has been reported. We
studied object manipulation in immature chimpanzees at Kalinzu (Uganda) and
bonobos at Wamba (Democratic Republic of Congo). We tested predictions of the
'preparation for tool use' hypothesis. We confirmed that chimpanzees showed
higher rates and more diverse types of object manipulation than bonobos. Against
expectation, male chimpanzees showed higher object manipulation rates than
females, whereas in bonobos no sex difference was found. However, object
manipulation by male chimpanzees was play-dominated, whereas manipulation types
of female chimpanzees were more diverse (e.g., bite, break, carry). Manipulation
by young immatures of both species was similarly dominated by play, but only in
chimpanzees did it become more diverse with age. Moreover, in chimpanzees, object
types became more tool-like (i.e., sticks) with age, further suggesting
preparation for tool use in adulthood. The male bias in object manipulation in
immature chimpanzees, along with the late onset of tool-like object manipulation,
indicates that not all (early) object manipulation (i.e., object play) in
immatures prepares for subsistence tool use. Instead, given the similarity with
gender differences in human children, object play may also function in motor
skill practice for male-specific behaviours (e.g., dominance displays). In
conclusion, even though immature behaviours almost certainly reflect preparation
for adult roles, more detailed future work is needed to disentangle possible
functions of object manipulation during development.
PMID- 26444012
TI - Using height-for-age differences (HAD) instead of height-for-age z-scores (HAZ)
for the meaningful measurement of population-level catch-up in linear growth in
children less than 5 years of age.
AB - BACKGROUND: Evidence from studies conducted in nutritionally deprived children in
low- and middle-income countries (LIMC) in past decades showed little or no
population-level catch-up in linear growth (mostly defined as reductions in the
absolute height deficit) after 2 years of age. Recent studies, however, have
reported population-level catch-up growth in children, defined as positive
changes in mean height-for-age z-scores (HAZ). The aim of this paper was to
assess whether population-level catch-up in linear growth is found when height
for-age difference (HAD: child's height compared to standard, expressed in
centimeters) is used instead of HAZ. Our premise is that HAZ is inappropriate to
measure changes in linear growth over time because they are constructed using
standard deviations from cross-sectional data. METHODS: We compare changes in
growth in populations of children between 2 and 5 years using HAD vs. HAZ using
cross-sectional data from 6 Demographic and Health Surveys (DHS) and longitudinal
data from the Young Lives and the Consortium on Health-Orientated Research in
Transitional Societies (COHORTS) studies. RESULTS: Using HAD, we find not only an
absence of population-level catch-up in linear growth, but a continued
deterioration reflected in a decrease in mean HAD between 2 and 5 years; by
contrast, HAZ shows either no change (DHS surveys) or an improvement in mean HAZ
(some of the longitudinal data). Population-level growth velocity was also lower
than expected (based on standards) in all four Young Lives data sets, confirming
the absence of catch-up growth in height. DISCUSSION: We show no evidence of
population-level catch-up in linear growth in children between 2 to 5 years of
age when using HAD (a measure more appropriate than HAZ to document changes as
populations of children age), but a continued deterioration reflected in a
decrease in mean HAD. CONCLUSIONS: The continued widening of the absolute height
deficit after 2 years of age does not challenge the critical importance of
investing in improving nutrition during the first 1000 days (i.e., from
conception to 2 years of age), but raises a number of research questions
including how to prevent continued deterioration and what is the potential of
children to benefit from nutrition interventions after 2 years of age.
Preventing, rather than reversing linear growth retardation remains the priority
for reducing the global burden of malnutritionworldwide.
PMID- 26444013
TI - Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with
Encephalitis.
AB - BACKGROUND: Encephalitis presents with seizures in the acute phase and increases
the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate
the effect of antiepileptic drugs in pediatric patients with acute seizures due
to encephalitis and epilepsy. PATIENTS AND METHODS: Cases of acute pediatric
encephalitis between January 2000 and December 2010 were reviewed. Clinical data,
including onset at age, seizure type, seizure frequency, effects of antiepileptic
drugs, and prognosis were analyzed. RESULTS: During the study period, 1038
patients (450 girls, 588 boys) were enrolled. Among them, 44.6% (463) had
seizures in the acute phase, 33% had status epilepticus, and 26% (251) developed
postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with
postencephalitic epilepsy were receiving antiepileptic drugs while 18% were
seizure free even after discontinuing the antiepileptic drugs. Among those with
postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti
epileptic drugs while 15% had intractable seizures and were using >= 2
antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was
preferred over phenytoin as treatment of postencephalitic seizures in the acute
phase. For refractory status epilepticus, high-dose topiramate combined with
intravenous high-dose phenobarbital or high-dose lidocaine had less side effects.
CONCLUSIONS: Children with encephalitis have a high rate of postencephalitic
epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or
in combination, for postencephalitic epilepsy.
PMID- 26444014
TI - KCl -Permeabilized Pancreatic Islets: An Experimental Model to Explore the
Messenger Role of ATP in the Mechanism of Insulin Secretion.
AB - Our previous work has demonstrated that islet depolarization with KCl opens
connexin36 hemichannels in beta-cells of mouse pancreatic islets allowing the
exchange of small metabolites with the extracellular medium. In this study, the
opening of these hemichannels has been further characterized in rat islets and
INS-1 cells. Taking advantage of hemicannels'opening, the uptake of extracellular
ATP and its effect on insulin release were investigated. 70 mM KCl stimulated
light emission by luciferin in dispersed rat islets cells transduced with the
fire-fly luciferase gene: it was suppressed by 20 mM glucose and 50 MUM
mefloquine, a specific connexin36 inhibitor. Extracellular ATP was taken up or
released by islets depolarized with 70 mM KCl at 5 mM glucose, depending on the
external ATP concentration. 1 mM ATP restored the loss of ATP induced by the
depolarization itself. ATP concentrations above 5 mM increased islet ATP content
and the ATP/ADP ratio. No ATP uptake occurred in non-depolarized or KCl
depolarized islets simultaneously incubated with 50 MUM mefloquine or 20 mM
glucose. Extracellular ATP potentiated the secretory response induced by 70 mM
KCl at 5 mM glucose in perifused rat islets: 5 mM ATP triggered a second phase of
insulin release after the initial peak triggered by KCl-depolarization itself; at
10 mM, it increased both the initial, KCl-dependent, peak and stimulated a
greater second phase of secretion than at 5 mM. These stimulatory effects of
extracellular ATP were almost completely suppressed by 50 MUM mefloquine. The
magnitude of the second phase of insulin release due to 5 mM extracellular ATP
was decreased by addition of 5 mM ADP (extracellular ATP/ADP ratio = 1). ATP acts
independently of KATP channels closure and its intracellular concentration and
its ATP/ADP ratio seems to regulate the magnitude of both the first (triggering)
and second (amplifying) phases of glucose-induced insulin secretion.
PMID- 26444015
TI - The Significance of Myriophyllum elatinoides for Swine Wastewater Treatment:
Abundance and Community Structure of Ammonia-Oxidizing Microorganisms in
Sediments.
AB - Myriophyllum elatinoides was reported to effectively treat wastewater by removing
nitrogen (N) and phosphorus (P). However, little is known about the abundance and
community structure of ammonia-oxidizing microorganisms associated with M.
elatinoides purification systems. The objective of this research was to
characterize the abundance and community structure of ammonia-oxidizing
microorganisms in swine wastewater and determine the main nitrogen removal
pathways. In this study, five different waters were treated by M. elatinoides in
microcosms for one month. The five waters included tap water (Control), swine
wastewater (SW), 50% diluted swine wastewater (50% SW), and two synthetic
wastewaters: 200 mg NH4+-N L(-1) (200 NH4+-N) and 400 mg NH4+-N L(-1) (400 NH4+
N). The most dramatic changes were in NH4+-N and total N (TN) concentrations,
with average removal rates of 84% and 90%, respectively, in the treatments
containing swine wastewater. On days 7, 14, and 28, the dissolved oxygen (DO)
increased by 81.8%, 210.4% and 136.5%, respectively, compared with on day 0, in
the swine wastewater. The results also showed that the bacterial amoA (AOB) copy
numbers in the sediments of the treatments were significantly higher than those
of archaeal amoA (AOA) copy numbers (p = 0.015). In addition, the high DO
concentrations in swine wastewater responded well to the high abundance of AOB.
The AOA and AOB community distributions were positively related with NO3-N and
were negatively related with DO in swine wastewater treatments. In summary, our
experimental results suggested that the M. elatinoides purification system could
improve the activity of ammonia-oxidizing microorganisms and consequently might
contribute to the significant N removal from the swine wastewater.
PMID- 26444016
TI - Polymorphism of the Oxytocin Receptor Gene Modulates Behavioral and Attitudinal
Trust among Men but Not Women.
AB - A relationship between the oxytocin receptor gene (OXTR) and behavioral and
attitudinal trust has been suggested, but the nature of this relationship has not
yet been established. We obtained behavioral trust data from 470 Japanese
participants (242 women) aged 20-59 years, together with their levels of general
trust and personality traits (NEO-FFI). Saliva buccal swabs were collected from
411 of these 470 participants and used for genotyping of OXTR rs53576. Our
participants were found to have more AA alleles (40%) than GG alleles (12%). The
GG men were more trusting and also rated higher on attitudinal trust than AA men,
and this difference did not diminish when personality traits were controlled for.
However, this pattern was not observed among women. In addition, controlling for
attitudinal trust reduced the difference in behavioral trust among men to a non
significant level, but the difference in attitudinal trust remained significant
when behavioral trust was controlled. These results indicate that the OXTR
genotype affects attitudinal trust as part of an individual's relatively stable
disposition, and further affects behavioral trust through changes in attitudinal
trust.
PMID- 26444018
TI - Hyaluronic acid increases tendon derived cell viability and collagen type I
expression in vitro: Comparative study of four different Hyaluronic acid
preparations by molecular weight.
AB - BACKGROUND: Hyaluronic Acid (HA) has been already approved by Food and Drug
Administration (FDA) for osteoarthritis (OA), while its use in the treatment of
tendinopathy is still debated. The aim of this study was to evaluate in human
rotator cuff tendon derived cells the effects of four different HA on cell
viability, proliferation, apoptosis and the expression of collagen type I and
collagen type III. METHODS: An in vitro model was developed on human tendon
derived cells from rotator cuff tears to study the effects of four different HA
preparations (Ps) (sodium hyaluronate MW: 500-730 KDa - Hyalgan(r), 1000 kDa
Artrosulfur HA(r), 1600 KDa Hyalubrix(r) and 2200 KDa Synolis-VA(r)) at various
concentrations. Tendon derived cells morphology were evaluated after 0, 7 and 14
d of culture. Viability, proliferation, apoptosis were evaluated after 0, 24 and
48 h of culture. The expression and deposition of collagen type I and collagen
type III were evaluated after 1, 7 and 14 d of culture. RESULTS: All HAPs tested
increased viability and proliferation, in dose dependent manner. HAPs already
reduce apoptosis at 24 h compared to control cells (without HAPs). Furthermore,
HAPs stimulated the synthesis of collagen type I in a dose dependent fashion over
14 d, without increase in collagen type III; moreover, in the presence of Synolis
VA(r) the expression and deposition of collagen type I was significantly higher
as compare with the other HAPs. CONCLUSIONS: HAPs enhanced viability,
proliferation and expression of collagen type I in tendon derived cells.
PMID- 26444017
TI - Endoplasmic Reticulum Stress-Induced Autophagy Provides Cytoprotection from
Chemical Hypoxia and Oxidant Injury and Ameliorates Renal Ischemia-Reperfusion
Injury.
AB - We examined whether endoplasmic reticulum (ER) stress-induced autophagy provides
cytoprotection from renal tubular epithelial cell injury due to oxidants and
chemical hypoxia in vitro, as well as from ischemia-reperfusion (IR) injury in
vivo. We demonstrate that the ER stress inducer tunicamycin triggers an unfolded
protein response, upregulates ER chaperone Grp78, and activates the autophagy
pathway in renal tubular epithelial cells in culture. Inhibition of ER stress
induced autophagy accelerated caspase-3 activation and cell death suggesting a
pro-survival role of ER stress-induced autophagy. Compared to wild-type cells,
autophagy-deficient MEFs subjected to ER stress had enhanced caspase-3 activation
and cell death, a finding that further supports the cytoprotective role of ER
stress-induced autophagy. Induction of autophagy by ER stress markedly afforded
cytoprotection from oxidants H2O2 and tert-Butyl hydroperoxide and from chemical
hypoxia induced by antimycin A. In contrast, inhibition of ER stress-induced
autophagy or autophagy-deficient cells markedly enhanced cell death in response
to oxidant injury and chemical hypoxia. In mouse kidney, similarly to renal
epithelial cells in culture, tunicamycin triggered ER stress, markedly
upregulated Grp78, and activated autophagy without impairing the autophagic flux.
In addition, ER stress-induced autophagy markedly ameliorated renal IR injury as
evident from significant improvement in renal function and histology. Inhibition
of autophagy by chloroquine markedly increased renal IR injury. These studies
highlight beneficial impact of ER stress-induced autophagy in renal ischemia
reperfusion injury both in vitro and in vivo.
PMID- 26444019
TI - Strategies for engaging with future radiation protection professionals: a public
outreach case study.
AB - It is evident that there is a nuclear skills shortage within the UK, and
logically it can be assumed that the shortfall extends to the radiation
protection arena. Plans for nuclear new-build and the decommissioning of existing
nuclear sites will require many more people with radiological knowledge and
practical competencies. This converts to a nuclear industry requirement in the
order of 1000 new recruits per year over at least the next ten years, mainly as
new apprentices and graduates. At the same time, the strong demand for persons
with radiation protection know-how in the non-nuclear and health care sectors is
unlikely to diminish. The task of filling this skills gap is a significant one
and it will require a determined effort from many UK stakeholders. The Society
for Radiological Protection (SRP) has adopted a strategy in recent years to help
address this skills gap. The aim is to engage the interest of secondary school
students in the science of radiation and inspire them to follow a career in
radiation protection. This paper presents the reasoning behind this strategy and,
in an 'outreach case study', describes the establishment of the annual SRP
Schools Event. This event is becoming an important addition to the national
efforts aimed at increasing the numbers of skilled UK radiation protection
professionals over the forthcoming decades.
PMID- 26444020
TI - Huntington's Disease in Arab Countries.
AB - Huntington's disease (HD) is an inherited neurodegenerative disorder. Involuntary
choreaform movements are the main symptom. The prevalence of HD in Arab countries
is not fully understood, as there are only a few reports indicating disease
incidence. Therefore, there is an urgent need for an investigation to determine
the frequency of HD in the Middle East, especially within Arab countries, and at
the same time enhance people's awareness of the disease.
PMID- 26444022
TI - Practice Effects and Stability of Neuropsychological and UHDRS Tests Over Short
Retest Intervals in Huntington Disease.
AB - BACKGROUND: In Huntington disease (HD), cognitive changes due to disease
progression or treatment are potentially confounded by "practice effects" (PE)-
performance improvement from prior exposure to test materials. OBJECTIVE: A
practice run-in ("dual baseline") was used in an HD cognitive trial to determine
if PE could be minimized and evaluate performance trajectories over multiple
visits. METHODS: Non-depressed adults (N = 36) with mild to moderate HD-related
cognitive deficits participated in a clinical trial to examine the efficacy of
citalopram to enhance cognition. Cognitive tests were administered at three
visits (2 weeks separating each visit), before active treatment randomization.
Some tests were also administered at screening. Therefore 3-4 pre-treatment
repetitions were available. We examined test improvement using repeated-measures
ANOVAs with planned pairwise comparisons. RESULTS: Despite the practice run-in
and use of alternate test forms, results indicated ongoing improvements over at
least three test sessions on all three UHDRS cognitive tests. Trails A and B
showed improvements between the third and fourth session, which suggests that one
pre-baseline visit may not be effective in reducing practice on this important
and commonly used test. CONCLUSIONS: Overall, 7 out of 13 variables showed some
degree of short-term PE, even after multiple sessions and alternate forms. Tests
assessing processing speed and memory may be particularly confounded by ongoing
PE across at least 2-3 sessions. Practice run-in periods and alternate forms may
help minimize the impact of such effects in HD clinical trials but awareness of
which tests are most susceptible to PE is important in clinical trial design.
PMID- 26444021
TI - Safety of Striatal Infusion of siRNA in a Transgenic Huntington's Disease Mouse
Model.
AB - BACKGROUND: The immune system In Huntington's disease (HD) is activated and may
overreact to some therapies. RNA interference using siRNA lowers mutant
huntingtin (mHTT) protein but could increase immune responses. OBJECTIVE: To
examine the innate immune response following siRNA infusion into the striatum of
wild-type (WT) and HD transgenic (YAC128) mice. METHODS: siRNAs (2'-O-methyl
phosphorothioated) were infused unilaterally into striatum of four month-old WT
and YAC128 mice for 28 days. Microglia number and morphology (resting (normal),
activated, dystrophic), cytokine levels, and DARPP32-positive neurons were
measured in striatum immediately or 14 days post-infusion. Controls included
contralateral untreated striatum, and PBS and sham treated striata. RESULTS: The
striata of untreated YAC128 mice had significantly fewer resting microglia and
more dystrophic microglia than WT mice, but no difference from WT in the
proportion of activated microglia or total number of microglia. siRNA infusion
increased the total number of microglia in YAC128 mice compared to PBS treated
and untreated striata and increased the proportion of activated microglia in WT
and YAC128 mice compared to untreated striata and sham treated groups. Cytokine
levels were low and siRNA infusion resulted in only modest changes in those
levels. siRNA infusion did not change the number of DARPP32-positive neurons.
CONCLUSION: Findings suggest that siRNA infusion may be a safe method for
lowering mHTT levels in the striatum in young animals, since treatment does not
produce a robust cytokine response or cause neurotoxicity. The potential long
term effects of a sustained increase in total and activated microglia after siRNA
infusion in HD mice need to be explored.
PMID- 26444023
TI - A Concept Map of What Helps People with HD Live with their Condition.
AB - BACKGROUND: The complex effects of Huntington's disease (HD) negatively impact on
every area of independent living. The perspectives of people impacted by HD on
how to best manage the disease are not clearly understood. OBJECTIVE: To identify
what is most helpful for living with HD from the perspectives of people with HD,
family caregivers and health professionals. METHODS: A cross-sectional, mixed
methods concept mapping methodology was used. Participants generated statements
during brainstorming in response to the question 'what helps people with HD live
with their condition'. Participants then prioritised statements for importance
and they grouped together statements that were related into clusters. Concept
mapping software ('Ariadne' (r)) used multi-dimensional scaling and hierarchical
cluster analysis to produce a conceptual framework of participants views about
what is helpful for people living with HD. RESULTS: Thirty nine people at various
stages of HD disease progression, 48 family caregivers and 39 health
professionals with experience of HD care (n = 126) participated. The most helpful
factors for living with HD were identified as access to expert assessment and
treatment for co-morbid mental health problems, integrated specialist multi
disciplinary HD expertise, and the provision of flexible care. CONCLUSIONS: HD
requires specialist, expert, multidisciplinary care teams to manage it well.
Specialists need to focus on the mental health aspects, and the provision must be
flexible and responsive to current needs. Patients may have impaired insight into
their abilities (e.g. driving) or the need for interventions, so carers' opinions
should also be respected.
PMID- 26444024
TI - Informativeness of Early Huntington Disease Signs about Gene Status.
AB - BACKGROUND: The cohort-level risk of Huntington disease (HD) is related to the
age and symptom level of the cohort, but this relationship has not been made
precise. OBJECTIVE: To predict the evolving likelihood of carrying the Huntington
disease (HD) gene for at-risk adults using age and sign level. METHODS: Using
data from adults with early signs and symptoms of HD linked to information on
genetic status, we use Bayes' theorem to calculate the probability that an
undiagnosed individual of a certain age and sign level has an expanded CAG
repeat. RESULTS: Both age and sign levels have substantial influence on the
likelihood of HD onset, and the probability of eventual diagnosis changes as
those at risk age and exhibit (or fail to exhibit) symptoms. For example, our
data suggest that in a cohort of individuals age 26 with a Unified Huntington's
Disease Rating Scale (UHDRS) motor score of 7-10 70% of them will carry the HD
mutation. For individuals age 56, the same motor score suggests only a 40% chance
of carrying the mutation. Early motor signs of HD, overall and the chorea
subscore, were highly predictive of disease onset at any age. However, body mass
index (BMI) and cognitive performance scores were not as highly predictive.
CONCLUSIONS: These results suggest that if researchers or clinicians are looking
for early clues of HD, it may be more foretelling to look at motor rather than
cognitive signs. Application of similar approaches could be used with other adult
onset genetic conditions.
PMID- 26444025
TI - The Genetic Modifiers of Motor OnsetAge (GeM MOA) Website: Genome-wide
Association Analysis for Genetic Modifiers of Huntington's Disease.
AB - BACKGROUND: Huntington's disease (HD) is a dominantly inherited disease caused by
a CAG expansion mutation in HTT. The age at onset of clinical symptoms is
determined primarily by the length of this CAG expansion but is also influenced
by other genetic and/or environmental factors. OBJECTIVE: Recently, through
genome-wide association studies (GWAS) aimed at discovering genetic modifiers, we
identified loci associated with age at onset of motor signs that are significant
at the genome-wide level. However, many additional HD modifiers may exist but may
not have achieved statistical significance due to limited power. METHODS: In
order to disseminate broadly the entire GWAS results and make them available to
complement alternative approaches, we have developed the internet website "GeM
MOA" where genetic association results can be searched by gene name, SNP ID, or
genomic coordinates of a region of interest. RESULTS: Users of the Genetic
Modifiers of Motor Onset Age (GeM MOA) site can therefore examine support for
association between any gene region and age at onset of HD motor signs. GeM MOA's
interactive interface also allows users to navigate the surrounding region and to
obtain association p-values for individual SNPs. CONCLUSIONS: Our website conveys
a comprehensive view of the genetic landscape of modifiers of HD from the
existing GWAS, and will provide the means to evaluate the potential influence of
genes of interest on the onset of HD. GeM MOA is freely available at
https://www.hdinhd.org/.
PMID- 26444027
TI - Subclinical pulmonary congestion is prevalent in nephrotic syndrome.
AB - In patients with nephrotic syndrome (NS), the lung is considered an organ
protected from the risk of edema. However, data on objectively measured lung
water in NS patients is lacking. Here we measured lung water by an ultrasound
(US) technique as well as by transthoracic impedance in 42 asymptomatic patients
with active NS, in 14 stage G5D CKD patients on chronic hemodialysis, and in 21
healthy individuals. In patients with active NS, the median number of US-B lines
(a metric of lung water) after 5 min in a supine position was significantly
higher (12; interquartile range: 7-25) compared with that in healthy individuals
(4; 2-9) but similar to that in hemodialysis patients (23; 10-39). The difference
between NS patients and healthy individuals was significantly amplified (16; 10
35 vs. 4; 2-9) after 60 min of supine resting and significantly attenuated after
5 min of standing (10; 7-25 vs. 3; 1-6). Posture-dependent changes in lung water
in patients with active NS were significantly accentuated compared with both
hemodialysis patients and healthy individuals. After NS remission, the number of
US-B lines was significantly reduced to 5 (4-18) at 5 min and to 6 (5-22) at 60
min approaching the normal range. Lung congestion in patients with active NS was
confirmed by transthoracic impedance. Thus, asymptomatic pulmonary congestion is
pervasive in patients with NS. A clinical trial is needed to assess the utility
of lung US for the management of patients with NS.
PMID- 26444028
TI - Src inhibition blocks renal interstitial fibroblast activation and ameliorates
renal fibrosis.
AB - Increased Src activity has been associated with the pathogenesis of renal tumors
and some glomerular diseases, but its role in renal interstitial fibrosis remains
elusive. To evaluate this, cultured renal interstitial fibroblasts (NRK-49F) were
treated with PP1, a selective inhibitor of Src. This resulted in decreased
expression of alpha-smooth muscle actin, fibronectin, and collagen I in response
to serum, angiotension II, or transforming growth factor-beta1 (TGF-beta1).
Silencing Src with siRNA also inhibited expression of those proteins.
Furthermore, inhibition of Src activity blocked renal fibroblast proliferation.
In a murine model of renal interstitial fibrosis induced by unilateral ureteral
obstruction, the active form of Src (phopsho-Src Tyr416) was upregulated in both
renal interstitial fibroblasts and renal tubular cells of the fibrotic kidney.
Its inactivation reduced renal fibroblast activation and attenuated extracellular
matrix protein deposition. Src inhibition also suppressed activation of TGF-beta1
signaling, activation of the epidermal growth factor receptor and STAT3, and
reduced the number of renal epithelial cells arrested at the G2/M phase of the
cell cycle after ureteral obstruction. Thus, Src is an important mediator of
renal interstitial fibroblast activation and renal fibrosis, and we suggest that
Src is a potential therapeutic target for treatment of chronic renal fibrosis.
PMID- 26444030
TI - Perioperative dexmedetomidine reduces the incidence and severity of acute kidney
injury following valvular heart surgery.
AB - Acute kidney injury (AKI) following cardiac surgery is closely interrelated with
hemodynamic instability and sympathetic activity, and adversely influences
prognosis. Here, we investigated in a randomized placebo-controlled trial whether
dexmedetomidine, an alpha2 adrenoreceptor agonist, could prevent AKI after
valvular heart surgery. Two hundred patients undergoing valvular heart surgery
were randomly assigned to equal placebo or treatment groups. Dexmedetomidine was
infused at a rate of 0.4 MUg/kg/h starting immediately after anesthetic induction
and continuing for 24 h after surgery. We then assessed the incidence of AKI
during the first 48 postoperative hours, hemodynamic variables, and a composite
of major morbidity end points. The incidence of AKI, based on Acute Kidney Injury
Network criteria, was significantly lower in the treatment group compared with
the control group (14 vs. 33%). The dexmedetomidine group exhibited a
significantly lower incidence of a composite of major morbidity end points (21
vs. 38%) and a significantly shorter length of intensive care unit stay (3 [2, 3]
days vs. 3 [2, 4] days) compared with the control group. Thus, perioperative
infusion of dexmedetomidine effectively reduced both the incidence and severity
of AKI, and improved outcome in patients undergoing valvular heart surgery
without untoward hemodynamic side effects.
PMID- 26444029
TI - Molecular mechanisms of insulin resistance in chronic kidney disease.
AB - Insulin resistance refers to reduced sensitivity of organs to insulin-initiated
biologic processes that result in metabolic defects. Insulin resistance is common
in patients with end-stage renal disease but also occurs in patients with chronic
kidney disease (CKD), even when the serum creatinine is minimally increased.
Following insulin binding to its receptor, auto-phosphorylation of the insulin
receptor is followed by kinase reactions that phosphorylate insulin receptor
substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and Akt. In fact, low
levels of Akt phosphorylation (p-Akt) identify the presence of the insulin
resistance that leads to metabolic defects in insulin-initiated metabolism of
glucose, lipids, and muscle proteins. Besides CKD, other complex conditions
(e.g., inflammation, oxidative stress, metabolic acidosis, aging, and excess
angiotensin II) reduce p-Akt resulting in insulin resistance. Insulin resistance
in each of these conditions is due to the activation of different E3 ubiquitin
ligases, which specifically conjugate ubiquitin to IRS-1 marking it for
degradation in the ubiquitin-proteasome system (UPS). Consequently, IRS-1
degradation suppresses insulin-induced intracellular signaling, causing insulin
resistance. Understanding mechanisms of insulin resistance could lead to
therapeutic strategies that improve the metabolism of patients with CKD.
PMID- 26444031
TI - Inhibition of H3K9 histone methyltransferase G9a attenuates renal fibrosis and
retains klotho expression.
AB - H3K9 methyltransferase G9a is reportedly induced by transforming growth factor
beta1 (TGF-beta1) and has an important role in the development of epithelial
mesenchymal transposition in cancer cells. Since the transcriptional activity of
the Klotho gene is regulated by H3K9 modification, we investigated the effects of
G9a on renal fibrosis and klotho expression. G9a levels were significantly
upregulated by day 7 in the kidneys of unilateral ureteral-obstructed mice, but
this was inhibited by TGF-beta1-neutralizing antibody. Administration of G9a
small interfering RNA not only decreased alpha-smooth muscle actin and
fibronectin but also increased klotho expression in the ureteral-obstructed mice.
Similarly, intraperitoneal injection of BIX01294, a specific inhibitor of G9a,
showed beneficial effects on renal fibrosis and klotho expression with decreased
monomethylation of H3K9 (me1). In in vitro experiments, BIX01294 also inhibited
TGF-beta1-induced fibrotic changes and klotho downregulation along with
suppressed H3K9me1. In human kidney biopsy specimens, areas of G9a immunostaining
correlated positively with H3K9me1 levels, as well as fibrotic markers, but
correlated negatively with klotho expression. Thus, TGF-beta1-induced G9a has an
important role in the progression of renal fibrosis and reduced klotho expression
through H3K9me1.
PMID- 26444032
TI - Super-resolution stimulated emission depletion imaging of slit diaphragm proteins
in optically cleared kidney tissue.
AB - The glomerular filtration barrier, consisting of podocyte foot processes with
bridging slit diaphragm, glomerular basement membrane, and endothelium, is a key
component for renal function. Previously, the subtlest elements of the filtration
barrier have only been visualized using electron microscopy. However, electron
microscopy is mostly restricted to ultrathin two-dimensional samples, and the
possibility to simultaneously visualize multiple different proteins is limited.
Therefore, we sought to implement a super-resolution immunofluorescence
microscopy protocol for the study of the filtration barrier in the kidney.
Recently, several optical clearing methods have been developed making it possible
to image through large volumes of tissue and even whole organs using light
microscopy. Here we found that hydrogel-based optical clearing is a beneficial
tool to study intact renal tissue at the nanometer scale. When imaging samples
using super-resolution STED microscopy, the staining quality was critical in
order to assess correct nanoscale information. The signal-to-noise ratio and
immunosignal homogeneity were both improved in optically cleared tissue. Thus,
STED of slit diaphragms in fluorescently labeled, optically cleared, intact
kidney samples is a new tool for studying the glomerular filtration barrier in
health and disease.
PMID- 26444033
TI - The Effect of Increasing Autonomy Through Choice on Young Children's Physical
Activity Behavior.
AB - BACKGROUND: Increasing autonomy by manipulating the choice of available physical
activity options in a laboratory setting can increase physical activity in older
children and adults. However, the effect of manipulating the number of physically
active choices has yet to be examined in young children in a gymnasium
environment. METHODS: Twenty children (n = 10 girls, 6.1 +/- 1.4 years old)
individually participated in 2 [low choice (LC), high choice (HC)] free-choice
activity conditions for 30 minutes in a 4360 square foot gymnasium. Children had
access to 2 or 8 physical activity options in the LC and HC conditions,
respectively. Physical activity behavior was measured via accelerometry. RESULTS:
Children's 30-minute accelerometer counts increased (P < .03) from the LC (2675
+/- 294 counts.min-1) to the HC (3224 +/- 280 counts.min-1) condition.
CONCLUSIONS: Providing greater autonomy through choice of a greater number of
physically active options increased young children's physical activity
participation by 20.5%.
PMID- 26444034
TI - Wurtzite-Phased InP Micropillars Grown on Silicon with Low Surface Recombination
Velocity.
AB - The direct growth of III-V nanostructures on silicon has shown great promise in
the integration of optoelectronics with silicon-based technologies. Our previous
work showed that scaling up nanostructures to microsize while maintaining high
quality heterogeneous integration opens a pathway toward a complete photonic
integrated circuit and high-efficiency cost-effective solar cells. In this paper,
we present a thorough material study of novel metastable InP micropillars
monolithically grown on silicon, focusing on two enabling aspects of this
technology-the stress relaxation mechanism at the heterogeneous interface and the
microstructure surface quality. Aberration-corrected transmission electron
microscopy studies show that InP grows directly on silicon without any amorphous
layer in between. A set of periodic dislocations was found at the
heterointerface, relaxing the 8% lattice mismatch between InP and Si. Single
crystalline InP therefore can grow on top of the fully relaxed template, yielding
high-quality micropillars with diameters expanding beyond 1 MUm. An interesting
power-dependence trend of carrier recombination lifetimes was captured for these
InP micropillars at room temperature, for the first time for
micro/nanostructures. By simply combining internal quantum efficiency with
carrier lifetime, we revealed the recombination dynamics of nonradiative and
radiative portions separately. A very low surface recombination velocity of 1.1 *
10(3) cm/sec was obtained. In addition, we experimentally estimated the radiative
recombination B coefficient of 2.0 * 10(-10) cm(3)/sec for pure wurtzite-phased
InP. These values are comparable with those obtained from InP bulk. Exceeding the
limits of conventional nanowires, our InP micropillars combine the strengths of
both nanostructures and bulk materials and will provide an avenue in
heterogeneous integration of III-V semiconductor materials onto silicon
platforms.
PMID- 26444036
TI - Efficient Electrochemical and Photoelectrochemical H2 Production from Water by a
Cobalt Dithiolene One-Dimensional Metal-Organic Surface.
AB - Solar-driven hydrogen evolution from water has emerged as an important
methodology for the storage of renewable energy in chemical bonds. Efficient and
practical clean-energy devices for electrochemical or photoelectrochemical
splitting of water require the immobilization of stable and active hydrogen
evolving catalysts onto electrode or photocathode materials, which remains a
significant challenge. Here we show that cobalt(II) reacts with benzene-1,2,4,5
tetrathiol in the presence of base to form a cobalt dithiolene polymer 1. The
generated polymer is immobilized onto glassy carbon electrodes (GCE) to generate
a metal-organic surface (MOS 1|GCE), which displays efficient H2-evolving
activity and stability in acidic aqueous solutions. Moreover, the generated
polymer is integrated with planar p-type Si to generate very efficient
photocathode materials (MOS 1|Si) for solar-driven hydrogen production from
water. Photocurrents up to 3.8 mA/cm(2) at 0 V vs RHE were achieved under
simulated 1 Sun illumination. MOS 1|Si photocathodes operate at potentials 550 mV
more positive than MOS 1|GCE cathodes to reach the same activity for H2 evolution
from water (1 mA/cm(2)).
PMID- 26444037
TI - Stabilizing and Improving Solar H2 Generation from Zn(0.5)Cd(0.5)S
Nanorods@MoS2/RGO Hybrids via Dual Charge Transfer Pathway.
AB - The incorporated Zn(0.5)Cd(0.5)S (ZCS) nanorods with MoS2/RGO cocatalysts by a
simultaneous reduction reaction was reported. The preparation of RGO and
formation of MoS2 with intimate interfacial contact with ZCS were achieved.
Through the optimizing of each component proportion, the ZCS@MoS2/RGO hybrid with
1.5 wt % MoS2 and 3 wt % RGO showed the highest photocatalytic H2 production
activity (2.31 mmol/h) with long time stability (50 h). The relative mechanism
has been investigated. It is believed that the stabilizing and improving solar H2
generation is originating from dual charge transfer pathway from excited ZCS to
RGO, then to MoS2 due to intimate interfacial structure.
PMID- 26444035
TI - Synthesis and Biological Evaluation of (S)-Amino-2-methyl-4-[(76)Br]bromo-3-(E)
butenoic Acid (BrVAIB) for Brain Tumor Imaging.
AB - The novel compound, (S)-amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic acid
(BrVAIB, [(76)Br]5), was characterized against the known system A tracer, IVAIB
([(123)I]8). [(76)Br]5 was prepared in a 51% +/- 19% radiochemical yield with
high radiochemical purity (>=98%). The biological properties of [(76)Br]5 were
compared with those of [(123)I]8. Results showed that [(76)Br]5 undergoes mixed
amino acid transport by system A and system L transport, while [(123)I]8 had less
uptake by system L. [(76)Br]5 demonstrated higher uptake than [(123)I]8 in DBT
tumors 1 h after injection (3.7 +/- 0.4% ID/g vs 1.5 +/- 0.3% ID/g) and also
showed higher uptake vs [(123)I]8 in normal brain. Small animal PET studies with
[(76)Br]5 demonstrated good tumor visualization of intracranial DBTs up to 24 h
with clearance from normal tissues. These results indicate that [(76)Br]5 is a
promising PET tracer for brain tumor imaging and lead compound for a mixed system
A and system L transport substrate.
PMID- 26444038
TI - Correction to Measurements of Methane Emissions from Natural Gas Gathering
Facilities and Processing Plants: Measurement Results.
PMID- 26444040
TI - ?
PMID- 26444039
TI - Differential Diagnosis of Cerebellar Atrophy in Childhood: An Update.
AB - Cerebellar atrophy (CA) is a relatively common, but nonspecific finding in
pediatric neurology and neuroradiology. Here, we provide an update of checklists
for postnatally acquired CA, unilateral CA, and hereditary CA. In addition, we
include a list of disorders with ataxia as a symptom, but without CA. These
checklists may help the evaluation of differential diagnosis and planning of
additional investigations. For diseases associated with hereditary CA, we provide
an updated version of our neuroimaging-based pattern-recognition approach that
classify CA as isolated ("pure") or associated ("plus") with other neuroimaging
findings including hypomyelination, progressive white matter abnormalities,
signal changes of the dentate nucleus, cerebellar cortex T2-hyperintensity, and
basal ganglia involvement. Finally, we discuss some rules with their exceptions
related to pediatric CA, discrepancies between clinical and neuroimaging course,
and the difficulties to differentiate CA from cerebellar hypoplasia.
PMID- 26444042
TI - ?
PMID- 26444041
TI - ?
PMID- 26444043
TI - Effects of self-generated versus experimenter-provided cues on the representation
of future events.
AB - Most experimental studies of prospection focused on episodic forms of future
events prompted by means of verbal cues. However, there is evidence suggesting
that future events differ considerably according to whether they are produced in
response to external, experimenter-provided verbal cues or they are self
generated. In the present study, we compared the quality, the phenomenal
characteristics, the temporal distribution, and the content of imagined events
prompted by experimenter-provided cues (i.e., cue-words and short verbal
sentences) or elicited by means of verbal cues that were self-generated in an
autobiographical fluency task. The results showed that future events prompted by
means of self-generated cues contained fewer event-specific details than future
events prompted by experimenter-provided cues. However, future events elicited by
means of self-generated and by experimenter-provided cues did not differ with
respect to their phenomenal characteristics. The temporal distribution and the
thematic content of future representations were also affected by the type of cue
used to elicit prospection. These results offer a holistic view of the properties
of future thinking and suggest that the content and the characteristics of
envisioned future events may be affected by the method used to elicit
prospection.
PMID- 26444044
TI - A Roundtable Discussion: Working Toward Safer, Easier-to-Use Infusion Systems.
PMID- 26444045
TI - IV Smart Pumps: The Impact of a Simplified User Interface on Clinical Use.
PMID- 26444046
TI - Eliminating Clinical Workarounds through Improved Smart Pump Drug Library Use.
PMID- 26444047
TI - Reducing Intermittent Infusion Syringe Pump Errors via Weight-Based Safety
Parameters.
AB - Historically, smart infusion pumps with dose error reduction software were
implemented to improve safety associated with programming of continuous infusion
modes on large-volume infusion pumps. Much of the published literature related to
smart infusion pumps and safety alerts is focused on continuous medication
infusions, with little available information related to their use with
intermittent infusions. As a result of the focus on continuous infusions, an
impression exists that intermittent infusions are less prone to programming
errors and/or do not require comparably rigorous safety parameters, such as use
of weight-based medication programming. METHODS: A retrospective study was
conducted with data from 10 pediatric inpatient hospitals, all of which used
syringe infusion pumps for intermittent medications, to describe the impact of
weight-based safety parameters on the occurrence of potential programming errors.
The data were analyzed based on recorded safety alerts and alert triggers for
weight-based (dose/kilogram/time) and non-weight-based (volume-over-time [VOT])
intermittent infusions. RESULTS: Data from a total of 4,162 pumps, 943,448 total
infusions, and 810,359 intermittent infusions between January 1 and December 31,
2013, were reviewed. Weight-based infusions had a greater percentage of safety
alerts (83.3%) compared with VOT infusions (16.7%). CONCLUSION: Weight-based
intermittent infusion modes can prevent programming errors and, compared with non
weight-based intermittent infusion modes, can be used to improve safety in the
pediatric population. Additional research should be conducted to confirm a
decrease in adverse drug events resulting from implementation of weight-based
safety parameters.
PMID- 26444048
TI - Ensuring Optimal Smart Pump Use Through Augmented User Interface.
PMID- 26444049
TI - Implementing Smart Infusion Pumps at Kaiser Permanente.
PMID- 26444051
TI - Umbilical blood gas analysis in preeclamptic versus healthy pregnancies with
preterm birth.
AB - OBJECTIVE: Comparing the value of umbilical cord arterial blood gas (UC-ABG)
analysis in the prediction of neonatal mortality and morbidity in the
preeclamptic versus healthy pregnancies with preterm birth. METHODS: Eight
hundred sixteen preterm (born at <37 gestational weeks) neonates with no other
morbidities who were born by cesarean section were evaluated. Immediately after
delivery, UC-ABG analysis was performed and the neonates were followed. RESULTS:
Preeclamptic women had lower umbilical cord blood (UCB) pH (7.2 4 +/- 0.1 versus
7.2 7 +/- 0.08, p = 0.008) and higher UCB base deficit (BD) (3.5 +/- 3.7 versus
2.2 +/- 3.4, p = 0.005) compared with controls. In the preeclamptic group, UCB
metabolic acidosis (pH < 7.15 and B.D > 8) was not independently associated with
neonatal morbidity or mortality, while in the control group UCB metabolic
acidosis was independently associated with low 10-min Apgar (OR, 4.9; 95%CI 1.37
18.03), respiratory distress syndrome (OR, 2.37; 95%CI 1.05-6.17),
intraventricular hemorrhage (OR, 3.01; 95%CI 1.13-7.99), and neonatal mortality
(OR, 17.33; 95%CI 4.51-66.53). CONCLUSIONS: The preterm neonates born to
preeclamptic mothers have lower UCB pH and higher BD. In these neonates, UCB
acidosis is not independently associated with any adverse neonatal outcomes. In
contrast, in the preterm neonates born to healthy mothers, UCB metabolic acidosis
is independently associated with neonatal mortality and morbidity.
PMID- 26444052
TI - Statistical media design for efficient polyhydroxyalkanoate production in
Pseudomonas sp. MNNG-S.
AB - Polyhydroxyalkanoate (PHA) is a promising polymer for various biomedical
applications. There is a high need to improve the production rate to achieve end
use. When a cost-effective production was carried out with cheaper agricultural
residues like molasses, traces of toxins were incorporated into the polymer,
which makes it unfit for biomedical applications. On the other hand, there is an
increase in the popularity of using chemically defined media for the production
of compounds with biomedical applications. However, these media do not exhibit
favorable characteristics such as efficient utilization at large scale compared
to complex media. This article aims to determine the specific nutritional
requirement of Pseudomonas sp. MNNG-S for efficient production of
polyhydroxyalkanoate. Response surface methodology (RSM) was used in this study
to statistically design for PHA production based on the interactive effect of
five significant variables (sucrose; potassium dihydrogen phosphate; ammonium
sulfate; magnesium sulfate; trace elements). The interactive effects of sucrose
with ammonium sulfate, ammonium sulfate with combined potassium phosphate, and
trace element with magnesium sulfate were found to be significant (p < .001). The
optimization approach adapted in this study increased the PHA production more
than fourfold (from 0.85 g L(-1) to 4.56 g L(-1)).
PMID- 26444053
TI - Exoskeletons for industrial application and their potential effects on physical
work load.
AB - The aim of this review was to provide an overview of assistive exoskeletons that
have specifically been developed for industrial purposes and to assess the
potential effect of these exoskeletons on reduction of physical loading on the
body. The search resulted in 40 papers describing 26 different industrial
exoskeletons, of which 19 were active (actuated) and 7 were passive (non
actuated). For 13 exoskeletons, the effect on physical loading has been
evaluated, mainly in terms of muscle activity. All passive exoskeletons retrieved
were aimed to support the low back. Ten-forty per cent reductions in back muscle
activity during dynamic lifting and static holding have been reported. Both lower
body, trunk and upper body regions could benefit from active exoskeletons. Muscle
activity reductions up to 80% have been reported as an effect of active
exoskeletons. Exoskeletons have the potential to considerably reduce the
underlying factors associated with work-related musculoskeletal injury.
Practitioner Summary: Worldwide, a significant interest in industrial
exoskeletons does exist, but a lack of specific safety standards and several
technical issues hinder mainstay practical use of exoskeletons in industry.
Specific issues include discomfort (for passive and active exoskeletons), weight
of device, alignment with human anatomy and kinematics, and detection of human
intention to enable smooth movement (for active exoskeletons).
PMID- 26444054
TI - Predictors of Recent Marijuana Use and Past Year Marijuana Use Among a National
Sample of Hispanic Youth.
AB - BACKGROUND: Marijuana use rates remain higher among Hispanic youth compared to
youth from other ethnic groups. OBJECTIVES: The purpose of the study was to
examine if sex, age, authoritarian parenting, perceived school experiences,
lifetime depression, legal involvement, and perceived social norms of marijuana
use predicted recent marijuana use and past year marijuana use among Hispanic
youth. METHODS: The participants of this study were a nationwide sample of
Hispanic youth (n = 3,457) in the United States. A secondary data analysis of the
2012 National Survey on Drug Use and Health was performed. Unadjusted odds ratios
were computed via univariate logistic regression analyses and all statistically
significant variables were retained and included in the final multiple logistic
regression analyses. Recent marijuana use was operationally defined as use within
the past 30 days, and marijuana use in the past year was defined as use within
the past year. RESULTS: Results indicated that 7.5% of Hispanic youth used within
the past month and 14.5% of Hispanic youth used within the past year. Results
revealed that significant predictors for recent use were age, authoritarian
parenting, perceived school experiences, legal involvement, and perceived social
norms of youth marijuana use. Predictors for past year were age, perceived school
experiences, legal involvement, and perceived social norms of youth marijuana
use. CONCLUSIONS/IMPORTANCE: Findings from this study can be used to address the
public health problem of marijuana use among Hispanic youth that is ultimately
contributing to health disparities among this ethnic group nationwide.
Recommendations for future studies are included.
PMID- 26444055
TI - Getting Warmer on Critical Care for Head Injury.
PMID- 26444056
TI - Cardioprotection and arrhythmias, Part I.
PMID- 26444057
TI - Cryptosporidium infections in birds--a review.
AB - Cryptosporidiosis is one of the main protozoan infections in birds. It manifests
as either a respiratory or a digestive illness, and it affects a very large
number of avian species across several continents. The aim of this review is to
report on the main results of studies on cryptosporidiosis among birds and the
importance of these results to veterinary medicine and public health.
PMID- 26444058
TI - Anthelmintic activity of Cymbopogon citratus against Haemonchus contortus.
AB - Parasitic nematodes are of major economic importance in livestock. An alternative
for the control of parasites is phytotherapy. This study evaluated the efficacy
of Cymbopogon citratus decoction (CcD), C. citratus essential oil (CcEo) and
citral against Haemonchus contortus using in vitro egg hatch test (EHT) and
larval development test (LDT) and an in vivo test using a Meriones unguiculatus
(gerbil) model. The effect of 800 mg/kg CcEo was evaluated in gerbils that had
been artificially infected with 5,000 third-stage H. contortus larvae. The
effective concentrations required to inhibit 50% (EC50) of egg hatching were
0.46, 0.14 and 0.13 mg/mL for CcD, CcEo and citral, respectively. The EC50 values
in the LDT were 5.04, 1.92 and 1.37 mg/mL for CcD, CcEo and citral, respectively.
H. contortus population in the group treated with C. citratus essential oil was
reduced by 38.5% (P< 0.05) in comparison to the control group. These results
suggest that it may be possible to use C. citratus essential oil to control of H.
contortus parasite of small ruminant.
PMID- 26444059
TI - Gastrointestinal and external parasites of the white-crested elaenia Elaenia
albiceps chilensis (Aves, Tyrannidae) in Chile.
AB - The objective of this study is to evaluate the ectoparasites and helminths of the
white-crested elaenia, Elaenia albiceps chilensis. Feather mites Anisophyllodes
elaeniae, Trouessartia elaeniae, and Analges sp. were detected in 51% of birds
(n=106), whereas 24% were infected with lice (Tyranniphilopterus delicatulus,
Menacanthus cfr. distinctus, and Ricinus cfr. invadens). Helminths Viguiera sp.
and Capillaria sp. were found in five of the birds that were necropsied (n=20).
With the exception of A. elaeniae, T. elaeniae, and T. delicatulus, all parasites
represented new records found for the white-crested elaenia, and therefore for
the Chilean repertoire of biodiversity.
PMID- 26444060
TI - Ectocommensal and ectoparasites in goldfish Carassius auratus (Linnaeus, 1758) in
farmed in the State of Sao Paulo.
AB - Concomitant infections by several parasitic genera are rare, very debilitating
and often lethal to fish reared under commercial breeding conditions. Were
describe a multiple and concurrent parasite infestation in cultured goldfish
Carassius auratus with skin damage (nodules and/or ulceration). Fish with skin
lesions underwent necropsy, and the skin and gills were scraped and examined.
Histopathological examination with Hematoxylin-Eosin and Giemsa stain, and an
ultrastructure study using transmission and scanning electron microscopy were
conducted. In the skin, we identified multiple-parasite infestations by
Gyrodactylidae, Epistylis sp., Trichodina sp., Ichthyophthirius multifiliis,
Tetrahymena sp. and Ichthyobodo necator,associated with epithelial cell
hyperplasia and epidermal sloughing. Although no gross lesions were observed,
were identified a large number of parasites in the gills (Epistylis sp.,
Piscinoodinium sp., Ichthyophthirius multifiliis, Trichodina sp., Apiosoma sp.,
Hexamitasp. and cysts of a trematode digenean). The observed trematodes were not
identified. The associated microscopic lesions were epithelial hypertrophic and
hyperplasic and exhibited fusion of secondary lamellae and epithelial cell
detachment. This is the first description of a protozoan Vorticella sp.
parasitizing goldfish in Brazil. Multiple ectoparasitism by protozoa and
Platyhelminthes, with or without apparent tissue damage, can be fatal for
goldfish raised on farms with poor management.
PMID- 26444061
TI - Expression of a recombinant protein, A2 family, from Leishmania infantum
(Jaboticabal strain) and its evaluation in Canine Visceral Leishmaniasis
serological test.
AB - This study aimed to express a recombinant A2 family protein of Leishmania
chagasi, Jaboticabal strain; test this protein as an antigen in serological
assays; and investigate its antigenicity and immunogenicity. A protein coded by
an allele of the A2 gene isolated from L. chagasi was expressed in three
different strains of Escherichia coli. We used 29 sera samples from Leishmune
vaccinated dogs, 482 sera samples from dogs from endemic areas (positive
controls), and 170 sera samples from dogs from non-endemic areas (negative
controls) in ELISA tests using soluble Leishmaniaantigen (SLA) and His-A2 as
antigen. Expressed proteins showed, by western blotting, the expression of an 11
KDa protein. Sixty-three percent (303/482) of the samples from endemic areas were
positive by ELISA His-A2, whereas 93.1% (27/29) of Leishmune(r)-vaccinated
animals were negative by His-A2-ELISA. Anti-A2 antibodies from mice inoculated
with the A2 protein were detected in slides containing amastigote forms, but not
in slides containing promastigote forms. The A2 recombinant protein from L.
chagasi may be a useful tool in the diagnosis of CVL, and further tests regarding
the infection stage and the specie of parasite at which the dogs are sampled
should provide a better understanding of our results.
PMID- 26444063
TI - New records of three species of nematodes in Cerdocyon thous from the Brazilian
Pantanal wetlands.
AB - We report the occurrence of nematodes collected from the gut of roadkilled crab
eating foxes (two adult males and one juvenile female), Cerdocyon thous
(Linnaeus, 1766), found on the BR 262 highway in Mato Grosso do Sul state, Brazil
in 2011. Three helminth species were identified: Ancylostoma buckleyi,
Pterygodermatites (Multipectines) pluripectinata, and Ascaridia galli. These
nematodes are reported for the first time to infect C. thous from the Brazilian
Pantanal wetlands, thereby expanding their geographical distribution.
PMID- 26444062
TI - Galectins and collectinis expression are increased in Haemonchus contortus
infected corriedale sheep.
AB - Galectins and collectins are proteins classified in the lectin family that have
the ability to recognize molecular patterns associated with pathogens. Studies on
cattle have demonstrated high expression of these proteins during infection with
gastrointestinal nematodes. The aim of this study was to investigate whether the
level of Haemonchus contortus infection would alter the expression of galectins
(Gal11 and Gal14) and collectins (SPA and CGN) in sheep. Twelve Corriedale sheep
exposed to natural infection with nematodes were divided into two groups: group 1
(G1, n = 7) and group 2 (G2, n = 5), with low and high parasite burdens,
respectively, based on fecal egg counts and abomasal parasite counts. The fecal
egg counts and abomasal parasite counts were significantly different (p < 0.05)
between the groups. Galectin and collectin gene expression was observed in all
sheep abomasal samples. However, animals with lower infection levels showed lower
expression of the genes Gal14, SPA and CGN (p < 0.05). Expression of lectins was
associated with the abomasal H. contortus burden, thus suggesting that these
proteins may have a role in controlling of this infection.
PMID- 26444064
TI - Antimicrobial activity of Stomoxys calcitrans against Beauveria bassiana sensu
lato isolates.
AB - This study had the aims of evaluating the antimicrobial characteristics of
Stomoxys calcitrans (Diptera: Muscidae) larvae against the fungal isolates CG138,
CG228 and ESALQ986 of Beauveria bassiana sensu lato (Balsamo-Crivelli) Vuillemin,
1912 (Hypocreales: Cordycipitaceae). S. calcitrans eggs, larvae and pupae were
exposed to these same isolates. Statistical analysis showed that the immature
stages of S. calcitrans were not susceptible to the fungal isolates used,
regardless of the exposure method. Diffusion test on solid culture medium reveled
that macerated S. calcitrans larvae exposed to isolate CG138 reduced CG138 fungal
development. The analysis of the chromatographic profiles indicated that the
macerate or mucus of larvae of the control group and the groups exposed to the
isolate CG138 presented different profiles. Reduced development of the isolate
CG138 on the larvae cuticle was observed by means of scanning electron
microscopy.
PMID- 26444065
TI - Brazilian donkeys (Equus asinus) have a low exposure to Neospora spp.
AB - Donkeys (Equus asinus) are closely related to horses and are known to be infected
by several equine pathogens. Neospora caninum and Neospora hughesi are protozoan
parasites that infect horses, but they were not confirmed in donkeys up to this
date. The aim of this study was to evaluate the exposure of donkeys (Equus
asinus) to Neospora spp. using tachyzoites of N. caninum as antigen and employing
two common serologic methods, IFAT and immunoblot. Sera from 500 donkeys were
obtained from 30 municipalities in Bahia state and tested by IFAT. Two of 500
sera were positive for Neospora spp. by IFAT with antibody titers of 100, and
recognized a 37kDa antigen in immunoblot. Approximately 22% of the samples showed
strong apical reactions and/or incomplete fluorescence, what may cause confusion
in the interpretation of IFAT. We concluded that Neospora spp. are possibly of
minor importance for Brazilian donkeys. Future studies are necessary to prove
that Neospora spp. can naturally infect donkeys.
PMID- 26444066
TI - Pathological and parasitological characterization of infection by trematodes
(Paramphistomatidae) in the large intestine of capybaras.
AB - Gross and histological lesions caused by an intestinal parasite were described in
three capybaras. The parasites presented a mean length of 14 mm and width of 7
mm, were round to oval or piriform, reddish and pedunculated, and adhered
strongly to the mucosa of the large intestine. The intestinal mucosa at the
parasite attachment site presented loss of surface epithelium and most glands,
with replacement by fibrovascular proliferation that protruded from the mucosa
and was involuted by the ventral sucker of the parasite. The lamina propria
presented cellular debris, eosinophils, macrophages and plasma cells. The
morphological characteristics, observed using serial histological sections, made
it possible to classify the parasite as a trematode (Paramphistomatidae),
compatible with Taxorchis schistocotyle. One capybara also harbored many ciliated
protozoa in the large intestine (at the site of attachment of the parasite) and
inside the caeca of the trematodes. In conclusion, this study described a
multifocal necrotizing colitis associated with T. schistocotyle parasitism in
capybaras.
PMID- 26444067
TI - Development and health status of Centropomus undecimalisparasitized by
Rhabdosynochus rhabdosynochus (Monogenea) under different salinity and
temperature conditions.
AB - This study evaluated the correlation of hematological parameters with the mean
abundance of the monogenean helminth Rhabdosynochus rhabdosynochus in Centropomus
undecimalis reared at different temperatures and salinities. The experimental
conditions were: 28 degrees C/0 ppt (parts per thousand); 28 degrees C/15 ppt;
28 degrees C/32 ppt; 25 degrees C/0 ppt; 25 degrees C/15 ppt; and 25 degrees
C/32 ppt. The prevalence was 100.0% in fish at 28 degrees C/15 ppt, 28 degrees
C/32 ppt and 25 degrees C/15 ppt, which was significantly different (p < 0.05)
from those at 25 degrees C/32 ppt. The red blood cell (RBC) count, hematocrit
and total leukocyte (WBC) count were significantly higher in fish at 28 degrees
C/15 ppt and 28 degrees C/32 ppt. The mean abundance of R. rhabdosynochus,
hematocrit and RBC showed positive correlations (P < 0.05) with temperature (rho=
0.3908; rho= 0.4771 and rho = 0.2812). Mean abundance showed negative
correlations with hemoglobin (rho= -0.3567) and mean corpuscular hemoglobin
concentration (MCHC) (rho = -0.2684). No correlation between abundance and
salinity was detected among the experimental conditions (rho = -0.0204). The low
numbers of monogeneans recorded (min -1 and max -33) explain the few changes to
fish health. This suggests that these experimental conditions may be recommended
for development of rearing of C. undecimalis in Brazil, without any influence or
economic losses from R. rhabdosynochus.
PMID- 26444068
TI - Toxoplasma gondii antibodies in wild rodents and marsupials from the Atlantic
Forest, state of Sao Paulo, Brazil.
AB - Toxoplasma gondii is a protozoan parasite that infects a large spectrum of warm
blooded animals, including humans. Small rodents and marsupials play an important
role in the epidemiology of T. gondii because they are sources of infection for
domestic and feral cats. Serum samples from 151 rodents and 48 marsupials,
captured in the Atlantic Forest, Sao Paulo State, southeastern Brazil, were
analyzed for the presence of T. gondii antibodies. Antibodies detected by the
modified agglutination test (MAT >= 25) were found in 8.6% (13/151) of the
rodents and 10.4% (5/48) of the marsupials, with titers ranging from 25 to 6400
and from 25 to 3200, respectively for the rodents and marsupials. Three of the
eight species of rodents (Akodon spp., Oligoryzomys nigripesand Rattus
norvegicus), and one from the four marsupial species (Didelphis aurita) presented
positive animals. T. gondii was described for the first time in the rodent
Oligoryzomys nigripes.
PMID- 26444070
TI - The Scholarship of Practice Within the Academic Clinical Enterprise.
PMID- 26444069
TI - Effect of growth factors on oocyte maturation and allocations of inner cell mass
and trophectoderm cells of cloned bovine embryos.
AB - This study was conducted to determine the additive effects of exogenous growth
factors during in vitro oocyte maturation (IVM) and the sequential culture of
nuclear transfer (NT) embryos. Oocyte maturation and culture of reconstructed
embryos derived from bovine granulosa cells were performed in culture medium
supplemented with either epidermal growth factor (EGF) alone or a combination of
EGF with insulin-like growth factor-I (IGF-I). The maturation rates of oocytes
matured in the presence of EGF or the EGF + IGF-I combination were significantly
higher than those of oocytes matured in the presence of only fetal calf serum
(FCS) (P 0.05). IGF-I alone or in combination with EGF in sequential embryo
culture medium significantly increased the ratio of inner cell mass (ICM) to
total blastocyst cells (P < 0.05). Our results showed that the addition of growth
factors to IVM and sequential culture media of cloned bovine embryos increased
the ICM without changing the total cell number. These unknown and uncontrolled
effects of growth factors can alter the allocation of ICM and trophectoderm cells
(TE) in NT embryos. A decrease in TE cell numbers could be a reason for
developmental abnormalities in embryos in the cloning system.
PMID- 26444071
TI - Target-Driven Evolution of Scorpion Toxins.
AB - It is long known that peptide neurotoxins derived from a diversity of venomous
animals evolve by positive selection following gene duplication, yet a force that
drives their adaptive evolution remains a mystery. By using maximum-likelihood
models of codon substitution, we analyzed molecular adaptation in scorpion sodium
channel toxins from a specific species and found ten positively selected sites,
six of which are located at the core-domain of scorpion alpha-toxins, a region
known to interact with two adjacent loops in the voltage-sensor domain (DIV) of
sodium channels, as validated by our newly constructed computational model of
toxin-channel complex. Despite the lack of positive selection signals in these
two loops, they accumulated extensive sequence variations by relaxed purifying
selection in prey and predators of scorpions. The evolutionary variability in the
toxin-bound regions of sodium channels indicates that accelerated substitutions
in the multigene family of scorpion toxins is a consequence of dealing with the
target diversity. This work presents an example of atypical co-evolution between
animal toxins and their molecular targets, in which toxins suffered from more
prominent selective pressure from the channels of their competitors. Our
discovery helps explain the evolutionary rationality of gene duplication of
toxins in a specific venomous species.
PMID- 26444072
TI - ITI-007 for the Treatment of Schizophrenia: A 4-Week Randomized, Double-Blind,
Controlled Trial.
AB - BACKGROUND: An urgent need exists for new treatments of schizophrenia that are
effective against a broad range of symptoms and free of limiting safety issues.
ITI-007 is a new molecular entity with a pharmacologic profile that combines dose
related monoamine modulation with phosphorylation of intracellular signaling
proteins. METHODS: A phase II randomized, double-blind, placebo-controlled, and
active-controlled trial was conducted at eight sites in the United States with
randomization of 335 acutely psychotic adults with schizophrenia. ITI-007 (60 mg
and 120 mg), placebo, and risperidone, included for assay sensitivity, were
evaluated as monotherapy for 4 weeks. The primary outcome measure was the
Positive and Negative Syndrome Scale total score, with secondary analyses
conducted on symptom subscales. RESULTS: ITI-007 60 mg (p = .017, effect size =
.4) and risperidone (p = .013, effect size = .4) demonstrated antipsychotic
efficacy superiority over placebo on the primary end point. The results of
secondary analyses reflected improvements in negative and depressive symptoms by
ITI-007 60 mg. ITI-007 120 mg did not separate from placebo. However, both doses
of ITI-007 were well tolerated in this patient population, as evidenced by low
discontinuation and adverse event rates, and were associated with a benign
metabolic profile as evidenced by significantly lower levels of prolactin,
fasting glucose, total cholesterol, and triglycerides than risperidone.
CONCLUSIONS: The mechanistically novel investigational drug ITI-007 was effective
for the treatment of schizophrenia and comparable with placebo on safety measures
in this trial. Secondary analyses indicated that ITI-007 improved negative and
depression symptoms and might have expanded therapeutic efficacy in comparison
with current antipsychotic drugs.
PMID- 26444073
TI - A Meta-Analysis of Mismatch Negativity in Schizophrenia: From Clinical Risk to
Disease Specificity and Progression.
AB - BACKGROUND: The observation that mismatch negativity (MMN) is consistently
impaired in schizophrenia has generated considerable interest in the use of this
biomarker as an index of disease risk and progression. Despite such enthusiasm, a
number of issues remain unresolved regarding the nature of MMN impairment. The
present study expands upon an earlier meta-analysis of MMN impairment in
schizophrenia by examining impairment across a range of clinical presentations,
as well as across experimental parameters. METHODS: One hundred one samples of
schizophrenia patients were included in the present study, including first
episode (n = 13), chronic (n = 13), and mixed-stage (n = 75) samples.
Additionally, MMN was examined in three related conditions: bipolar disorder (n =
9), unaffected first-degree relatives (n = 8), and clinical high risk (n = 16).
RESULTS: We found that MMN impairment 1) likely reflects a vulnerability to
disease progression in clinical high-risk populations rather than a genetic risk
for the condition; 2) is largely unrelated to duration of illness after the first
few years of illness, indicating that impairment is not progressive throughout
the life span; 3) is present in bipolar disorder, albeit to a lesser degree than
in schizophrenia; and 4) is not modulated by experimental parameters such as
magnitude of change between standard and deviant tones or frequency of deviant
tones but may be modulated by attentional demands. CONCLUSIONS: Such findings lay
the foundation for a better understanding of the nature of MMN impairment in
schizophrenia, as well as its potential as a clinically useful biomarker.
PMID- 26444074
TI - Prenatal Caffeine Exposure and Child IQ at Age 5.5 Years: The EDEN Mother-Child
Cohort.
AB - BACKGROUND: Evidence from animal studies suggests maternal caffeine intake during
pregnancy has detrimental effects on subsequent brain development in offspring.
However, human data in this area are limited. The aim of this study was to assess
whether caffeine intake by women during pregnancy is associated with impaired
cognitive development in offspring at age 5.5 years. METHODS: Multivariate
modeling was conducted using data of 1083 mother-child pairs from a population
based birth cohort in France followed from pregnancy to age 5.5 years of the
children. Measures included an estimate of maternal caffeine intake during
pregnancy, children's IQ at age 5.5, and individual and family characteristics.
RESULTS: Prenatal caffeine exposure was common in the sample (91%) with 12%
displaying an intake >=200 mg/day (high). Multivariable modeling showed a
significant negative relationship between caffeine intake and children's IQ at
5.5 years (-.94 [95% confidence interval = -1.70, -.17] full IQ unit per 100 mg
daily caffeine intake). In particular, children of mothers consuming >=200 mg/day
were more likely to have borderline or lower IQ compared with children of mothers
consuming <100 mg/day (13.5% vs. 7.3%; odds ratio = 2.30, 95% confidence interval
= 1.13, 4.69). CONCLUSIONS: We found an association between caffeine intake
during pregnancy and impaired cognitive development in offspring, a result in
line with animal data. More epidemiologic and biologically grounded research is
needed to determine whether this association is causal. This finding suggests
that conservative guidelines regarding the maximum caffeine intake recommended in
pregnancy (i.e., 200 mg/day) should be maintained.
PMID- 26444075
TI - Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large
European Cohort.
AB - BACKGROUND: Gilles de la Tourette syndrome (GTS) is a complex neuropsychiatric
disorder with a strong genetic influence where copy number variations are
suggested to play a role in disease pathogenesis. In a previous small-scale copy
number variation study of a GTS cohort (n = 111), recurrent exon-affecting
microdeletions of four genes, including the gene encoding arylacetamide
deacetylase (AADAC), were observed and merited further investigations. METHODS:
We screened a Danish cohort of 243 GTS patients and 1571 control subjects for
submicroscopic deletions and duplications of these four genes. The most promising
candidate gene, AADAC, identified in this Danish discovery sample was further
investigated in cohorts from Iceland, the Netherlands, Hungary, Germany, and
Italy, and a final meta-analysis, including a total of 1181 GTS patients and
118,730 control subjects from these six European countries, was performed.
Subsequently, expression of the candidate gene in the central nervous system was
investigated using human and mouse brain tissues. RESULTS: In the Danish cohort,
we identified eight patients with overlapping deletions of AADAC. Investigation
of the additional five countries showed a significant association between the
AADAC deletion and GTS, and a final meta-analysis confirmed the significant
association (p = 4.4 * 10(-4); odds ratio = 1.9; 95% confidence interval = 1.33
2.71). Furthermore, RNA in situ hybridization and reverse transcription
polymerase chain reaction studies revealed that AADAC is expressed in several
brain regions previously implicated in GTS pathology. CONCLUSIONS: AADAC is a
candidate susceptibility factor for GTS and the present findings warrant further
genomic and functional studies to investigate the role of this gene in the
pathogenesis of GTS.
PMID- 26444077
TI - Motor intensive anti-gravity training improves performance in dynamic balance
related tasks in persons with Parkinson's disease.
AB - Recent studies indicate that the effect of training on motor performance in
persons with Parkinson's disease (PDP) is dependent on motor intensity. However,
training of high motor intensity can be hard to apply in PDP due to e.g.
bradykinesia, rigidity, tremor and postural instability. Therefore, the aim was
to study the effect of motor intensive training performed in a safe anti-gravity
environment using lower-body positive pressure (LBPP) technology on performance
during dynamic balance related tasks. Thirteen male PDP went through an 8-week
control period followed by 8 weeks of motor intensive antigravity training.
Seventeen healthy males constituted a control group (CON). Performance during a
five repetition sit-to-stand test (STS; sagittal plane) and a dynamic postural
balance test (DPB; transversal plane) was evaluated. Effect measures were
completion time, functional rates of force development, directional changes and
force variance. STS completion time improved by 24% to the level of CON which was
explained by shorter sitting-time and standing-time and larger numeric rate of
force change during lowering to the chair, indicating faster vertical directional
change and improved relaxation. DPB completion time tended to improve and was
accompanied by improvements of functional medial and lateral rates of force
development and higher vertical force variance during DPB. Our results suggest
that the performance improvements may relate to improved inter-limb coordination.
It is concluded that 8 weeks of motor intensive training in a safe LBPP
environment improved performance during dynamic balance related tasks in PDP.
PMID- 26444078
TI - Changes in serotonin (5-HT) and brain-derived neurotrophic factor (BDFN)
expression in frontal cortex and hippocampus of aged rat treated with high
tryptophan diet.
AB - Age-related cognitive decline is accompanied by an alteration in neurotransmitter
synthesis and a dysregulation of neuroplasticity-related molecules such as
serotonin (5-HT) and brain-derived neurotrophic factor (BDFN). It has been
previously demonstrated that hyperserotonemia induced by l-Tryptophan (TrP)
enriched diet protect against memory deficits during physiological aging. Since 5
HT is closely associated to BDNF, we aimed to investigate the effect of high TrP
diet on 5-HT levels and BDNF expression in Frontal Cortex (FC) and Hippocampus
(Hp) of aged rats. We found that the raising of systemic 5-HT levels by chronic
diet (1 month) containing high TrP significantly prevents age-related decline of
BDNF protein expression in both brain areas as indicated by ELISA and Western
Blot analyses. Interestingly, immunohistochemical analyses confirmed that high
TrP diet significantly elevates the number of 5-HT immunoreactive fibers in both
brain areas tested and this correlated with BDNF increase in the FC and
hippocampal regions CA1, CA2, CA3 and a strikingly down-regulation of
neurotrophin levels in the dentate gyrus (DG) of aged rats. Altogether, these
finding provide evidence that enhanced TrP intake and the consequent increase in
5-HT neurotransmission may act as a modulator of BDNF system suggesting a
possible mechanism for the protective role of serotonergic system on memory
impairment occurring along normal aging process.
PMID- 26444076
TI - Maternal Exposure to Childhood Trauma Is Associated During Pregnancy With
Placental-Fetal Stress Physiology.
AB - BACKGROUND: The effects of exposure to childhood trauma (CT) may be transmitted
across generations; however, the time period(s) and mechanism(s) have yet to be
clarified. We address the hypothesis that intergenerational transmission may
begin during intrauterine life via the effect of maternal CT exposure on
placental-fetal stress physiology, specifically placental corticotropin-releasing
hormone (pCRH). METHODS: The study was conducted in a sociodemographically
diverse cohort of 295 pregnant women. CT exposure was assessed using the
Childhood Trauma Questionnaire. Placental CRH concentrations were quantified in
maternal blood collected serially over the course of gestation. Linear mixed
effects and Bayesian piece-wise linear models were employed to test hypothesized
relationships. RESULTS: Maternal CT exposure (CT+) was significantly associated
with pCRH production. Compared with nonexposed women, CT+ was associated with an
almost 25% increase in pCRH toward the end of gestation, and the pCRH trajectory
of CT+ women exhibited an approximately twofold steeper increase after the pCRH
inflection point at 19 weeks gestation. CONCLUSIONS: To the best of our
knowledge, this finding represents the first report linking maternal CT exposure
with placental-fetal stress physiology, thus identifying a potential novel
biological pathway of intergenerational transmission that may operate as early as
during intrauterine life.
PMID- 26444079
TI - Possible neural network mediating jaw opening during prey-catching behavior of
the frog.
AB - The prey-catching behavior of the frog is a complex, well-timed sequence of
stimulus response chain of movements. After visual analysis of the prey, a size
dependent program is selected in the motor pattern generator of the brainstem.
Besides this predetermined feeding program, various direct and indirect sensory
inputs provide flexible adjustment for the optimal contraction of the executive
muscles. The aim of the present study was to investigate whether trigeminal
primary afferents establish direct contacts with the jaw opening motoneurons
innervated by the facial nerve. The experiments were carried out on Rana
esculenta (Pelophylax esculentus), where the trigeminal and facial nerves were
labeled simultaneously with different fluorescent dyes. Using a confocal laser
scanning microscope, close appositions were detected between trigeminal afferent
fibers and somatodendritic components of the facial motoneurons. Quantitative
analysis revealed that the majority of close contacts were encountered on the
dendrites of facial motoneurons and approximately 10% of them were located on the
perikarya. We suggest that the identified contacts between the trigeminal
afferents and facial motoneurons presented here may be one of the morphological
substrate in the feedback and feedforward modulation of the rapidly changing
activity of the jaw opening muscle during the prey-catching behavior.
PMID- 26444080
TI - Effects of loading misalignment and tapering angle on the measured mechanical
properties of nanowires.
AB - Loading misalignment and tapering of nanowires are usually unavoidable factors in
compression and tensile mechanical property testing of nanowires. Herein, we
report quantitative finite element analyses and experimental measurements on how
these two factors affect the measured compression and tensile mechanical
properties if they are not included in the data analysis. The results obtained
show that ignoring these two factors leads to different degrees of
underestimation of the critical load, Young's modulus and tensile fracture
strength.
PMID- 26444081
TI - Silent IL2RG Gene Editing in Human Pluripotent Stem Cells.
AB - Many applications of pluripotent stem cells (PSCs) require efficient editing of
silent chromosomal genes. Here, we show that a major limitation in isolating
edited clones is silencing of the selectable marker cassette after homologous
recombination and that this can be overcome by using a ubiquitous chromatin
opening element (UCOE) promoter-driven transgene. We use this strategy to edit
the silent IL2RG locus in human PSCs with a recombinant adeno-associated virus
(rAAV)-targeting vector in the absence of potentially genotoxic, site-specific
nucleases and show that IL2RG is required for natural killer and T-cell
differentiation of human PSCs. Insertion of an active UCOE promoter into a silent
locus altered the histone modification and cytosine methylation pattern of
surrounding chromatin, but these changes resolved when the UCOE promoter was
removed. This same approach could be used to correct IL2RG mutations in X-linked
severe combined immunodeficiency patient-derived induced PSCs (iPSCs), to prevent
graft versus host disease in regenerative medicine applications, or to edit other
silent genes.
PMID- 26444082
TI - Grapefruit-derived Nanovectors Delivering Therapeutic miR17 Through an Intranasal
Route Inhibit Brain Tumor Progression.
AB - The lack of access to the brain is a major obstacle for central nervous system
drug development. In this study, we demonstrate the capability of a grapefruit
derived nanovector (GNV) to carry miR17 for therapeutic treatment of mouse brain
tumor. We show that GNVs coated with folic acid (FA-GNVs) are enhanced for
targeting the GNVs to a folate receptor-positive GL-26 brain tumor. Additionally,
FA-GNV-coated polyethylenimine (FA-pGNVs) not only enhance the capacity to carry
RNA, but the toxicity of the polyethylenimine is eliminated by the GNVs.
Intranasal administration of miR17 carried by FA-pGNVs led to rapid delivery of
miR17 to the brain that was selectively taken up by GL-26 tumor cells. Mice
treated intranasally with FA-pGNV/miR17 had delayed brain tumor growth. Our
results demonstrate that this strategy may provide a noninvasive therapeutic
approach for treating brain-related disease through intranasal delivery.
PMID- 26444084
TI - Global Materials Structure Search with Chemically Motivated Coordinates.
AB - Identification of relevant reaction pathways in ever more complex composite
materials and nanostructures poses a central challenge to computational materials
discovery. Efficient global structure search, tailored to identify chemically
relevant intermediates, could provide the necessary first-principles atomistic
insight to enable a rational process design. In this work we modify a common
feature of global geometry optimization schemes by employing automatically
generated collective curvilinear coordinates. The similarity of these coordinates
to molecular vibrations enhances the generation of chemically meaningful trial
structures for covalently bound systems. In the application to hydrogenated Si
clusters, we concomitantly observe a significantly increased efficiency in
identifying low-energy structures and exploit it for an extensive sampling of
potential products of silicon-cluster soft landing on Si(001) surfaces.
PMID- 26444083
TI - Host Anti-antibody Responses Following Adeno-associated Virus-mediated Delivery
of Antibodies Against HIV and SIV in Rhesus Monkeys.
AB - Long-term delivery of antibodies against the human immunodeficiency virus (HIV)
using adeno-associated virus (AAV) vectors is a promising approach for the
prevention or treatment of HIV infection. However, host antibody responses to the
delivered antibody are a serious concern that could significantly limit the
applicability of this approach. Here, we describe the dynamics and
characteristics of the anti-antibody responses in monkeys that received either
rhesus anti-simian immunodeficiency virus (SIV) antibodies (4L6 or 5L7) in
prevention trials or a combination of rhesusized human anti-HIV antibodies
(1NC9/8ANC195/3BNC117 or 10-1074/10E8/3BNC117) in therapy trials, all employing
AAV1 delivery of IgG1. Eight out of eight monkeys that received the anti-HIV
antibodies made persisting antibody responses to all three antibodies in the mix.
Six out of six uninfected monkeys that received the anti-SIV antibody 4L6 and
three out of six of those receiving anti-SIV antibody 5L7 also generated anti
antibodies. Both heavy and light chains were targeted, predominantly or
exclusively to variable regions, and reactivity to complementarity-determining
region (CDR)-H3 peptide could be demonstrated. There was a highly significant
correlation of the magnitude of anti-antibody responses with the degree of
sequence divergence of the delivered antibody from germline. Our results suggest
the need for effective strategies to counteract the problem of antibody responses
to AAV-delivered antibodies.
PMID- 26444085
TI - Objectively Measured School Day Physical Activity Among Elementary Students in
the United States and Finland.
AB - BACKGROUND: Schools are in a unique position to ensure that all students meet the
current physical activity (PA) recommendations. This study aimed to examine 1st
to 3rd grade elementary students' accelerometer measured school day PA in the
United States (U.S.) and Finland. METHODS: The sample consisted of 200 students
(107 girls, 93 boys; ages 6 to 8) and their school day PA was monitored with hip
worn ActiGraph GT3X+ accelerometers across a 5-day school week and the thresholds
100 and 2296 count per minute were used to separate sedentary time, light PA, and
moderate-to-vigorous PA (MVPA). RESULTS: On an average school day, students were
engaged in MVPA for 20.0 min in the U.S. and 24.1 min in Finland. Students'
school-day MVPA was 9 to 16 minutes higher during physical education (PE) days
compared with non-PE days (U.S: 25.8 vs. 16.6 min/day; Finland: 36.3 vs. 20.1
min/day). Girls had less MVPA and more sedentary time compared with boys in both
samples. CONCLUSION: This study highlights both the role of PE and other school
day physical activities in meeting PA guidelines. Policy measures are needed to
change the structure of the school day and enhance PA to ensure that students
meet the PA recommendations.
PMID- 26444086
TI - String Vessel Formation is Increased in the Brain of Parkinson Disease.
AB - BACKGROUND: String vessels are collapsed basement membrane without endothelium
and have no function in circulation. String vessel formation contributes to
vascular degeneration in Alzheimer disease. By comparing to age-matched control
cases we have recently reported endothelial degeneration in brain capillaries of
human Parkinson disease (PD). OBJECTIVE: Current study evaluated changes of
basement membrane of capillaries, string vessel formation and their association
with astrocytes, blood-brain-barrier integrity and neuronal degeneration in PD.
METHODS: Brain tissue from human cases of PD and age-matched controls was used.
Immunohistochemical staining for collagen IV, GFAP, NeuN, tyrosine hydroxylase,
fibrinogen and Factor VIII was evaluated by image analysis in the substantia
nigra, caudate nucleus and middle frontal gyrus. RESULTS: While the basement
membrane-associated vessel density was similar between the two groups, the
density of string vessels was significantly increased in the PD cases,
particularly in the substantia nigra. Neuronal degeneration was found in all
brain regions. Astrocytes and fibrinogen were increased in the caudate nuclei of
PD cases compared with control cases. CONCLUSIONS: Endothelial degeneration and
preservation of basement membrane result in an increase of string vessel
formation in PD. The data may suggest a possible role for cerebral hypoperfusion
in the neuronal degeneration characteristic of PD, which needs further
investigation. Elevated astrocytosis in the caudate nucleus of PD cases could be
associated with disruption of the blood-brain barrier in this brain region.
PMID- 26444087
TI - Risk of Disabling Response Fluctuations and Dyskinesias for Dopamine Agonists
Versus Levodopa in Parkinson's Disease.
AB - BACKGROUND: Response fluctuations and dyskinesias develop during the use of both
levodopa (LD) and dopamine agonists (DA), but may not be equally disabling.
OBJECTIVE: To compare the risk and time of onset of disabling response
fluctuations and dyskinesias (DRFD) among patients with Parkinson's disease (PD)
who were initially treated with either LD or DA. METHODS: Open cohort study of
all consecutive de-novo PD patients in routine clinical practice, included over a
period of 15 years (median follow-up: 8.1 years, range 1.1-17.7), since embarking
on LD or DA. Older patients and patients with more severe PD were started on LD
(n = 77), younger patients on a DA (n = 50). Therapy was adjusted according to
generally accepted guidelines. The primary endpoints were: the onset of response
fluctuations, dyskinesias, and the moment when these complications became
disabling (DRFD). RESULTS: LD-starters developed response fluctuations 0.8 years
earlier than DA-starters (p = 0.07), while dyskinesias appeared around 2.5 years
earlier (p = 0.003). However, the risk and time of onset of DRFD did not differ
statistically between the groups (LD-starters: 60% , median interval 7.3 years,
DA-starters: 52% , 6.1 years, p = 0.63). DA-starters displayed a 0.19 points
lower adjusted mean improvement in motor scores than LD-starters (p = 0.002).
Adjustments for age and severity of PD at start of dopaminergic therapy did not
change these results. CONCLUSIONS: In routine clinical practice, the risk and
time of onset of DRFD is comparable for LD-starters versus DA-starters, but motor
functioning is worse in DA-starters. These results support the use of LD as
initial therapy for PD.
PMID- 26444088
TI - Freezing of Gait and its Associations in the Early and Advanced Clinical Motor
Stages of Parkinson's Disease: A Cross-Sectional Study.
AB - BACKGROUND: Freezing of gait is a common disabling symptom of Parkinson's disease
(PD) with limited treatment options. The pathophysiological mechanisms of
freezing behaviour are still contentious. OBJECTIVE: To investigate the
prevalence of freezing of gait and its associations with increasing disease
severity to gain a better understanding of the underlying pathophysiology.
METHODS: This exploratory study included 389 idiopathic PD patients, divided into
four groups; early and advanced PD with freezing of gait, and early and advanced
PD without freezing of gait. Motor, cognitive and affective symptoms, REM sleep
behaviour disorder and autonomic function were assessed. RESULTS: Regardless of
disease stage, patients with freezing of gait had more severe motor symptoms and
a predominant non-tremor phenotype. In the early stages, freezers had a selective
impairment in executive function and had more marked REM sleep behaviour
disorder. Autonomic disturbances were not associated with freezing of gait across
early or advanced disease stages. CONCLUSION: These findings support the notion
that impairments across the frontostriatal pathways are intricately linked to the
pathophysiology underlying freezing of gait across all stages of PD. Features of
REM sleep behaviour disorder suggest a contribution to freezing from brainstem
pathology but this does not extend to more general autonomic dysfunction.
PMID- 26444089
TI - Knowledge of Parkinson's Disease in a Multiethnic Urban Asian Setting.
AB - BACKGROUND: Public knowledge regarding Parkinson's disease (PD) is important to
facilitate good health-seeking behavior, but the literature on this topic is
scarce. OBJECTIVE: We aimed to explore the level of public knowledge regarding PD
in a large multiethnic urban Asian cohort, and (as a secondary aim) in a smaller
cohort of PD patients and caregivers. METHODS: A Knowledge of PD Questionnaire
(KPDQ) was developed and administered to members of the Malaysian general public,
and to PD patients and caregivers. The KPDQ tests recognition of PD symptoms and
general knowledge regarding PD. RESULTS: 1,258 members of the general public
completed the KPDQ. Tremor was the most widely recognized symptom (recognized by
79.0% of respondents); however, 83.7% incorrectly believed that all PD patients
experience tremor. Memory problem was the most widely recognized NMS. Overall,
motor symptoms were better recognized than NMS. Common misperceptions were that
there is a cure for PD (49.8%) and that PD is usually familial (41.4%). Female
gender, Chinese ethnicity, tertiary education, healthcare-related work, and
knowing someone with PD were independently associated with higher KPDQ scores. PD
patients (n = 116) and caregivers (n = 135) demonstrated superior knowledge
compared with the general public group, but one-third of them believed that PD is
currently curable. CONCLUSIONS: This is the only study on public knowledge
regarding PD in Asia. Important gaps in knowledge were evident, which could
present a barrier to early diagnosis and appropriate treatment of PD. This
highlights the need for targeted education campaigns and further research in this
area.
PMID- 26444090
TI - Conversion to IPX066 from Standard Levodopa Formulations in Advanced Parkinson's
Disease: Experience in Clinical Trials.
AB - BACKGROUND: Due to the short half-life of levodopa, immediate-release carbidopa
levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a
risk of eventual motor complications. IPX066 was designed to rapidly attain
therapeutic LD concentrations and maintain them to allow a dosing interval of ~6
hours. OBJECTIVE: To extensively analyze the dosing data collected in IPX066
studies during open-label conversions from IR CD-LD alone or with entacapone
(CLE) and identify patterns relevant for managing conversion in the clinical
setting. METHODS: Patients had >=2.5 hours/day of "off" time despite a stable IR
or CLE regimen. Suggested initial dosing conversion tables based on prior LD
daily dosage were provided. RESULTS: Of 450 patients previously treated with IR
CD-LD and 110 with CLE, 87.3% and 82.7% completed conversion to IPX066,
respectively. At the end of conversion, average IPX066 LD daily dosages were
higher than pre-conversion dosages, with a mean conversion ratio of 2.1+/-0.6 for
IR CD-LD and 2.8+/-0.8 for CLE; >90% of patients took IPX066 3 or 4 times/day,
compared with a median of 5 times/day at baseline in both studies. After
conversion, daily "off" time significantly decreased, with no significant
increase in troublesome dyskinesia. The most common adverse event reported during
conversion was nausea, with an incidence of 5.3% for conversion from IR and 7.3%
from CLE. CONCLUSIONS: Among PD patients with substantial "off" time, a majority
were safely converted to IPX066. The sustained LD profile from the IPX066
formulation allowed an increase in LD dose accompanied by improved motor
functions, without increased troublesome dyskinesia.
PMID- 26444091
TI - Occupational Characteristics and Patterns as Risk Factors for Parkinson's
Disease: A Case Control Study.
AB - BACKGROUND: Associations have been reported between the risk of Parkinson's
disease (PD) and employment in certain fields. Most studies have focused on toxic
exposures as potential causal explanations. However, PD also has been associated
with personality characteristics that may influence occupational choices and
patterns. OBJECTIVE: This study evaluates the role of personality as indicated by
occupational choices and employment patterns in the risk for PD. METHODS: In
person interviews were conducted to assess occupational histories and early-adult
personality indicators among 89 PD patients and 99 controls. RESULTS: PD cases
had fewer lifetime jobs than controls (mean for cases = 4.38 +/- 2.20; mean for
controls = 5.00 +/- 2.26; p = 0.03). Among women, PD was positively associated
with more complex work with people (OR = 1.45, 95% CI 1.12-1.89), representing a
95% increased risk for PD comparing women with the greatest complexity of work
with those requiring the least complexity of work with people. Women PD cases
also performed less complex work with things compared with controls (OR = 0.69
(95% CI 0.53-0.90)), translating into a 13-fold increased risk for PD among women
whose work involved the least complex work with things compared with the most.
The numbers of jobs and job types were associated with taking more activity risks
as a young-adult (r = 0.19, p = 0.02; r = 0.26, p = 0.001, respectively).
CONCLUSIONS: Cases with PD held fewer lifetime jobs compared with controls.
Occupational complexity was associated with the risk for PD among women, but not
men. Further consideration of the possible influence of personality on
occupational choices is warranted.
PMID- 26444092
TI - A Positive 'Pointing Test' in a Parkinson's Disease Patient.
PMID- 26444093
TI - Disability is an Independent Predictor of Falls and Recurrent Falls in People
with Parkinson's Disease Without a History of Falls: A One-Year Prospective
Study.
AB - BACKGROUND: Predictors of falls in people with Parkinson's disease (PD) who have
not previously fallen are yet to be identified. OBJECTIVES: We aimed to identify
predictors of all falls and recurrent falls in people with PD who had not fallen
in the previous year and to explore the timing of falls in a 12-month follow-up
period. METHODS: Participants with PD (n = 130) were assessed by disease
specific, self-report and balance measures. Falls were recorded prospectively for
12 months. Univariate and multivariate analyses were performed. Kaplan-Meier
survival analysis was used to investigate time to falling. RESULTS: Forty
participants (31%) had >=1 fall during follow-up and 21 (16%) had >=2 falls.
Disability, reduced balance confidence and greater concern about falling were
associated with >=1 fall in univariate analyses. Additionally, PD duration and
severity, freezing of gait and impaired balance were associated with >=2 falls (p
< 0.05). Disability (Schwab and England scale, Odds Ratio [OR] = 0.56 per 10
points increase; 95% confidence interval [CI] 0.39-0.80; p = 0.002) was
associated with >=1 fall in the final multivariate model (area under the receiver
operating characteristic curve [AUC] = 0.65; 95% CI 0.55-0.76; p = 0.005).
Disability (Unified Parkinson's Disease Rating Scale activities of daily living,
OR = 1.20; 95% CI 1.07-1.34; p = 0.001) and levodopa equivalent dose (OR = 1.11
per 100 mg increase; 95% CI 0.95-1.30; p = 0.19) were associated with >=2 falls
in the final multivariate model (AUC = 0.72; 95% CI 0.60-0.84; p = 0.001).
Recurrent fallers experienced their first fall earlier than single fallers (p <
0.05). CONCLUSIONS: Self-reported disability was the strongest single predictor
of all falls and recurrent falls.
PMID- 26444094
TI - Anticholinergic Load: Is there a Cognitive Cost in Early Parkinson's Disease?
AB - We evaluated the effect of anticholinergic burden on 219 participants with
incident Parkinson's disease (PD) and 99 controls at study baseline and 18
months. Anticholinergic burden for each individual was calculated and summed
according to the Anticholinergic Drug Scale (ADS). Medication with
anticholinergic activity was more commonly prescribed in PD compared to controls,
although mean ADS scores were not significantly different. Cognitive scores did
not differ in PD participants taking medications with anticholinergic activity
compared to those who were not. Low overall ADS scores due to increased awareness
of adverse effects of medications and brevity of follow-up are potential
explanations.
PMID- 26444096
TI - Multidisciplinary Collaboration in Professional Networks for PD A Mixed-Method
Analysis.
AB - BACKGROUND: ParkinsonNet, a nationwide organization with regionally oriented
professional health networks in TheNetherlands, aims to improve the quality of
Parkinson care. Facilitation of multidisciplinary collaboration is a key
objective of ParkinsonNet. OBJECTIVES: This study examined whether the concept
enhances multidisciplinary collaboration between healthcare professionals
involved in Parkinson care. METHODS: A regional network involving 101 healthcare
professionals was newly established. Participants received two questionnaires.
One aimed at documenting direct working relationships ('connections') between
professionals and the other aimed at evaluating multidisciplinary team
performance. Additionally, thirteen healthcare professionals were interviewed to
identify barriers and facilitators for multidisciplinary collaboration. 'Social
network analysis' focused on sub-networks around three community hospitals at
baseline and one year after the implementation. RESULTS: The number of 'knowing
each other' connections increased from 1431 to 2175 (52% , p < 0.001) and
'professional contact' connections increased from 664 to 891 (34% , p < 0.001).
Large differences between sub-networks were found, positive changes being
associated with a central role of neurologists and nurse specialists committed to
multidisciplinary care. The perceived team performance did not change.
Participants experienced problems with information exchange and interdisciplinary
communication. Generally, participants were unaware of other healthcare
professionals involved in individual patients and what treatments they provide
simultaneously. CONCLUSIONS: ParkinsonNet partially enhanced multidisciplinary
collaboration between healthcare professionals involved in Parkinson care.
Crucial facilitators of this were a central role of nurse specialists and the
commitment to collaborate with and refer to expert therapists among neurologists.
Additional measures are needed to further improve multidisciplinary care across
different institutions and around individual patients.
PMID- 26444097
TI - Unravelling the Proton Conduction Mechanism from Room Temperature to 553 K in a
3D Inorganic Coordination Framework.
AB - The preparation of proton-conducting materials that are functional and stable at
intermediate temperatures (393-573 K) is a focal point of fuel cell development.
The purely inorganic material, HNd(IO3)4, which possesses a dense 3D framework
structure, can reach a maximum of 4.6 * 10(-4) S.cm(-1) at 353 K and 95% relative
humidity and exhibit a high conductivity of 8.0 * 10(-5) S.cm(-1) from 373 to 553
K under the flow of wet N2. HNd(IO3)4 exhibits a variety of improvements
including high thermal stability, low solubility in water, and resistance to
reducing atmosphere. The proton conductivity in such a wide temperature range
originates from the intrinsic liberated protons in the structure and the
resulting 1D hydrogen-bonding network confirmed by bond valence sum calculation
and solid-state NMR analysis. Moreover, two different activation energies are
observed in different temperature regions (0.23 eV below 373 K and 0.026 eV from
373 to 553 K), indicating that two types of proton motion are responsible for
proton diffusion, as further domenstrated by temperature-dependent open-circuit
voltage hysteresis in a tested fuel cell assembly as well as variable-temperature
and double quantum filtered solid-state NMR measurements.
PMID- 26444095
TI - Peripheral Biomarkers of Parkinson's Disease Progression and Pioglitazone
Effects.
AB - Pioglitazone, an oral hypoglycemic agent, recently failed to show promise as a
disease-modifying agent in a 44-week phase 2 placebo-controlled study in 210
Parkinson's disease (PD) subjects. We analyzed peripheral biomarkers, including
leukocyte PGC-1alpha and target gene expression, plasma interleukin 6 (IL-6) as a
marker of inflammation, and urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of
oxidative DNA damage. Baseline or changes from baseline in biomarker levels were
not associated with the rate of progression of PD. Pioglitazone did not
significantly alter biomarker levels. Other agents that more effectively target
these mechanisms remain of potential interest as disease modifying therapies in
PD.
PMID- 26444098
TI - Anti-inflammatory Inositol Derivatives from the Whole Plant of Inula cappa.
AB - Twelve new inositol derivatives, classified into myoinositol (1-6) and l-inositol
(10-15) types, along with five known analogues were isolated from the whole plant
of Inula cappa. The structures of the new compounds were established by extensive
analysis of mass spectrometric and 1D and 2D NMR spectroscopic data. All the
tested compounds showed anti-inflammatory activities against the production of NO
in RAW264.7 macrophages stimulated by lipopolysaccharide, with IC50 values
ranging from 7 to 23 MUM.
PMID- 26444100
TI - Catalytic Role of Multinuclear Palladium-Oxygen Intermediates in Aerobic
Oxidation Followed by Hydrogen Peroxide Disproportionation.
AB - Aerobic oxidation of alcohols are catalyzed by the Pd-acetate compound
[LPd(OAc)]2(OTf)2 (L = neocuproine = 2,9-dimethyl-1,10-phenanthroline) to form
ketones and the release of hydrogen peroxide, but the latter rapidly undergoes
disproportionation. We employ a series of kinetic and isotope labeling studies
made largely possible by electrospray ionization mass spectrometry to determine
the role of intermediates in causing this complex chemical transformation. The
data suggested that multiple catalytic paths for H2O2 disproportionation occur,
which involve formation and consumption of multinuclear Pd species. We find that
the trinuclear compound [(LPd)3(MU(3)-O)2](2+), which we have identified in a
previous study, is a product of dioxygen activation that is formed during aerobic
oxidations of alcohols catalyzed by [LPd(OAc)]2(OTf)2. It is also a product of
hydrogen peroxide activation during disproportionation reactions catalyzed by
[LPd(OAc)]2(OTf)2. The results suggest that this trinuclear Pd compound is
involved in one of the simultaneous mechanisms for the reduction of oxygen and/or
the disproportionation of hydrogen peroxide during oxidation catalysis.
Electrospray ionization mass spectrometry of hydrogen peroxide disproportionation
reactions suggested the presence of other multinuclear Pd-O2 species in solution.
Theoretical calculations of these compounds yield some insight into their
structure and potential chemistry.
PMID- 26444099
TI - Chlorabietols A-C, Phloroglucinol-Diterpene Adducts from the Chloranthaceae Plant
Chloranthus oldhamii.
AB - Three unprecedented phloroglucinol-diterpene adducts, chlorabietols A-C (1-3),
were isolated from the roots of the rare Chloranthaceae plant Chloranthus
oldhamii. They represent a new class of compounds, featuring an abietane-type
diterpenoid coupled with different alkenyl phloroglucinol units by forming a 2,3
dihydrofuran ring. Their structures were elucidated by detailed spectroscopic
analysis, molecular modeling studies, and electronic circular dichroism
calculations. Compounds 1-3 showed inhibitory activity against protein tyrosine
phosphatase 1B (PTP1B) with IC50 values of 12.6, 5.3, and 4.9 MUM, respectively.
PMID- 26444101
TI - Dissociative Photoionization of Diethyl Ether.
AB - The dissociative photoionization of internal energy selected diethyl ether ions
was investigated by imaging photoelectron photoion coincidence spectroscopy. In a
large, 5 eV energy range Et2O(+) cations decay by two parallel and three
sequential dissociative photoionization channels, which can be modeled well using
statistical theory. The 0 K appearance energies of the CH3CHOCH2CH3(+) (H-loss,
m/z = 73) and CH3CH2O?CH2(+) (methyl-loss, m/z = 59) fragment ions were
determined to be 10.419 +/- 0.015 and 10.484 +/- 0.008 eV, respectively. The
reemergence of the hydrogen-loss ion above 11 eV is attributed to transition
state (TS) switching, in which the second, outer TS is rate-determining at high
internal energies. At 11.81 +/- 0.05 eV, a secondary fragment of the
CH3CHOCH2CH3(+) (m/z = 73) ion, protonated acetaldehyde, CH3CH?OH(+) (m/z = 45)
appears. On the basis of the known thermochemical onset of this fragment, a
reverse barrier of 325 meV was found. Two more sequential dissociation reactions
were examined, namely, ethylene and formaldehyde losses from the methyl-loss
daughter ion. The 0 K appearance energies of 11.85 +/- 0.07 and 12.20 +/- 0.08
eV, respectively, indicate no reverse barrier in these processes. The statistical
model of the dissociative photoionization can also be used to predict the
fractional ion abundances in threshold photoionization at large temperatures,
which could be of use in, for example, combustion diagnostics.
PMID- 26444102
TI - Tuning Phase Composition of TiO2 by Sn(4+) Doping for Efficient Photocatalytic
Hydrogen Generation.
AB - The anatase-rutile mixed-phase photocatalysts have attracted extensive research
interest because of the superior activity compared to their single phase
counterparts. In this study, doping of Sn(4+) ions into the lattice of TiO2
facilitates the phase transformation from anatase to rutile at a lower
temperature while maintaining the same crystal sizes compared to the conventional
annealling approach. The mass ratios between anatase and rutile phases can be
easily manipulated by varying the Sn-dopant content. Characterization results
reveal that the Sn(4+) ions entered into the lattice of TiO2 by substituting some
of the Ti(4+) ions and distributed evenly in the matrix of TiO2. The substitution
induced the distortion of the lattice structure, which realized the phase
transformation from anatase to rutile at a lower temperature and the close
contact phase junctions were consequently formed between anatase and rutile,
accounting for the efficient charge separations. The mixed-phase catalysts
prepared by doping Sn(4+) ions into the TiO2 exhibit superior activity for
photocatalytic hydrogen generation in the presence of Au nanoparticles,
relatively to their counterparts prepared by the conventional annealling at
higher temperatures. The band allignment between anatase and rutile phases is
established based on the valence band X-ray photoelectron spectra and diffuse
reflectance spectra to understand the spatial charge separation process at the
heterojunction between the two phases. The study provides a new route for the
synthesis of mixed-phase TiO2 catalysts for photocatalytic applications and
advances the understanding on the enhanced photocatalytic properties of anatase
rutile mixtures.
PMID- 26444103
TI - Use of Immunomodulators and Biologics Before, During, and After Pregnancy.
AB - Immunomodulators and biologic medications, alone or in combination, form the core
therapeutic strategy for managing moderate-to-severe inflammatory bowel disease
(IBD). IBD incidence peaks during the prime reproductive years, raising concerns
about the impact of disease and its treatment on fertility, maternal and fetal
health during pregnancy, breastfeeding safety, and childhood development.
Although IBD increases risk of pregnancy complications independent of disease
activity, adverse pregnancy outcomes are more common when disease is active. To
mitigate fetal risk, women should conceive while disease is quiescent. Aside from
methotrexate, immunomodulators and biologics may be used during pregnancy to
achieve and maintain disease control. Based on available safety data, there is no
increased risk of congenital anomalies among infants exposed to these
medications. Active thiopurine metabolites and most monoclonal antibodies cross
the placenta and are detectable in neonates. They are detectable in breast milk
in minute levels as well. The impact of this exposure on neonatal outcomes is
discussed. Adjusted dosing schedules during gestation may reduce fetal drug
exposure, though the maternal risks of such manipulation require careful
consideration. Ongoing prospective studies will further inform risk assessment,
including for newer medications such as the anti-integrin agents.
PMID- 26444104
TI - Genome-based Definition of an Inflammatory Bowel Disease-associated Adherent
Invasive Escherichia coli Pathovar.
AB - BACKGROUND: Mucosal-associated Escherichia coli are commonly found in inflamed
tissues during inflammatory bowel disease (IBD). These bacteria often possess an
adherent and invasive phenotype but lack virulence-associated features of well
described intestinal E. coli pathogens, and are of diverse serology and
phylotypes, making it difficult to correlate strain characteristics with
exacerbations of disease. METHODS: The genome sequences of 14 phenotypically
assigned adherent-invasive Escherichia coli (AIEC) isolates obtained from
intestinal biopsies of patients with IBD were compared with the genome sequences
of 37 other pathogenic and commensal E. coli available from public databases.
RESULTS: Core genome-based phylogenetic analyses and genome-wide comparison of
genetic content established the existence of a closely related cluster of AIEC
strains with 3 distinct genetic insertions differentiating them from commensal E.
coli. These strains are of the B2 phylotype have a variant type VI secretion
system (T6SS-1), and are highly related to extraintestinal pathogenic E. coli,
suggesting that these 2 clinically distinct pathovars have common virulence
strategies. Four other mucosally adherent E. coli strains from patients with IBD
were of diverse phylogenetic origins and lacked the 3 genetic features,
suggesting that they are not related to the B2 AIEC cluster. Although AIEC are
often considered as having a unique association with Crohn's disease, isolates
from Crohn's disease and ulcerative colitis were genetically indistinguishable.
CONCLUSIONS: B2 AIEC thus represent a closely related cluster of IBD-associated
E. coli strains that are distinct from normal commensal isolates, and which
should be considered separately from the phenotypically similar but genetically
distinct non-B2 AIEC strains when considering their association with intestinal
pathogenesis.
PMID- 26444105
TI - Rapid Stereocomplexation between Enantiomeric Comb-Shaped Cellulose-g-poly(L
lactide) Nanohybrids and Poly(D-lactide) from the Melt.
AB - In this work we report the in situ preparation of fully biobased stereocomplex
poly(lactide) (SC-PLA) nanocomposites grafted onto nanocrystalline cellulose
(NCC). The stereocomplexation rate by compounding high-molar-mass poly(D-lactide)
(PDLA) with comb-like NCC grafted poly(L-lactide) is rather high in comparison
with mixtures of PDLA and PLLA. The rapid stereocomplexation was evidenced by a
high stereocomplexation temperature (Tc-sc = 145 degrees C) and a high SC
crystallinity (Xc-sc = 38%) upon fast cooling (50 degrees C/min) from the melt
(250 degrees C for 2 min), which are higher than currently reported values.
Moreover, the half-life crystallization time (175-190 degrees C) of the SC-PLA
was shortened by 84-92% in comparison with the PDLA/PLLA blends. The high(er)
stereocomplexation rate and the melt stability of the SC in the nanocomposites
were ascribed to the nucleation effect of the chemically bonded NCC and the
"memory effect" of molecular pairs in the stereocomplex melt because of the
confined freedom of the grafted PLLA chains.
PMID- 26444106
TI - Maternal Influenza Vaccination and Risk for Congenital Malformations: A
Systematic Review and Meta-analysis.
AB - OBJECTIVE: To systematically summarize the literature on maternal influenza
vaccination and the risk for congenital malformations using the methodology of
meta-analysis. DATA SOURCES: PubMed, Scopus, and Embase databases (up to December
2014) as well as ClinicalTrials.gov (May 2015) and references of relevant
articles were searched. The search strategy included combinations of the terms
"influenza," "vaccin*," "pregnan*," "safe*," "adverse," "congenital,"
"malformation," "defect," and "anomal*." METHODS OF STUDY SELECTION: Eligible
studies examined the association between antepartum or preconceptional maternal
immunization with inactivated influenza vaccines (seasonal trivalent or
monovalent H1N1) and the risk for congenital malformations. Studies with no or
inappropriate control group (comparison with population background rates or other
vaccine types) were excluded. TABULATION, INTEGRATION, AND RESULTS: The risk for
congenital anomalies after influenza vaccination was examined in 15 studies: 14
cohorts (events per vaccinated compared with unvaccinated: 859/32,774 [2.6%]
compared with 7,644/245,314 [3.1%]) and one case-control study (vaccinated per
cases compared with controls: 1,351/3,618 [37.3%] compared with 511/1,225
[41.7%]). Eight studies reported on first-trimester immunization (events per
vaccinated compared with unvaccinated: 258/4,733 [5.4%] compared with
6,470/196,054 [3.3%]). No association was found between congenital defects and
influenza vaccination at any trimester of pregnancy (odds ratio [OR] 0.96, 95%
confidence interval 0.86-1.07; 15 studies; I2=36) or at the first trimester (OR
1.03, 0.91-1.18; eight studies; I2=0). When assessing only major malformations,
no increased risk was detected after immunization at any trimester (OR 0.99, 0.88
1.11; 12 studies; I2=31.5) or at the first trimester (OR 0.98, 0.83-1.16; seven
studies; I2=0). Neither adjuvanted (OR 1.06, 0.95-1.20; five studies; I2=18.8)
nor unadjuvanted vaccines (OR 0.89, 0.75-1.04; seven studies; I2=22.6) were
associated with an increased risk for congenital defects. CONCLUSION: This
systematic review did not indicate an increased risk for congenital anomalies
after maternal influenza immunization adding to the evidence base on the safety
of influenza vaccination in pregnancy.
PMID- 26444108
TI - Current Status of Testing for Microdeletion Syndromes and Rare Autosomal
Trisomies Using Cell-Free DNA Technology.
AB - Noninvasive prenatal testing using cell-free DNA in maternal blood for trisomy 21
was introduced in 2011. This technology has continuously evolved with the
addition of screening for trisomy 18 and trisomy 13 followed by the inclusion of
sex chromosome aneuploidies. Expanded noninvasive prenatal test panels have
recently become available, which enable screening for microdeletion syndromes
such as the 22q11.2 deletion (associated with the velocardiofacial syndrome) and
others. However, the performance data for these microdeletion syndromes are
derived from a small number of samples, mostly generated in vitro. Rigorous
performance evaluation, as was done at least for trisomy 21 testing using cell
free DNA analysis, is difficult to perform given the rarity of each condition. In
addition, detection rates may vary considerably depending on deletion size.
Importantly, positive predictive values (PPVs), strongly influenced by the low
prevalence, are expected to be significantly lower than 10% for most conditions.
Thus, screening in an average-risk population is likely to have many more false
positives than affected cases detected. Conversely, testing in a high-risk
population such as fetuses with cardiac anomalies may have higher PPVs, but a
negative result needs to be considered carefully as a result of uncertain
information about detection rates and a significant residual risk for other copy
number variants and single gene disorders. This article integrates current
knowledge on cell-free DNA testing for microdeletions with the aim to assist
clinicians and policymakers in designing optimal programs for screening in
pregnancy.
PMID- 26444107
TI - Predicting Cesarean Delivery After Induction of Labor Among Nulliparous Women at
Term.
AB - OBJECTIVE: To identify independent risk factors for cesarean delivery after
induction of labor and to develop a nomogram for predicting cesarean delivery
among nulliparous women undergoing induction of labor at term. METHODS: This is a
retrospective cohort study including nulliparous women with singleton, term (37
0/7 weeks of gestation or greater), cephalic pregnancies undergoing induction of
labor from July 1, 2006, through May 31, 2012, at a tertiary care academic
center. Inductions were identified using International Classification of
Diseases, 9th Revision codes. Demographic, delivery, and outcome data were
abstracted manually from the medical record. Women with a contraindication to
vaginal delivery (malpresentation, abnormal placentation, prior myomectomy) were
excluded. Independent risk factors for cesarean delivery were identified using
logistic regression. RESULTS: During the study period, there were 785 nulliparous
inductions that met study criteria; 231 (29.4%) underwent cesarean delivery.
Independent risk factors associated with an increased risk of cesarean delivery
included older maternal age, shorter maternal height, greater body mass index,
greater weight gain during pregnancy, older gestational age, hypertension,
diabetes mellitus, and initial cervical dilation less than 3 cm. A nomogram was
constructed based on the final model with a bias-corrected c-index of 0.709 (95%
confidence interval 0.671-0.750). CONCLUSION: We identified independent risk
factors that can be used to predict cesarean delivery among nulliparous women
undergoing induction of labor at term. If validated in other populations, the
nomogram could be useful for individualized counseling of women with a
combination of identifiable antepartum risk factors. LEVEL OF EVIDENCE: II.
PMID- 26444109
TI - Safety of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis and
Influenza Vaccinations in Pregnancy.
AB - OBJECTIVE: To evaluate the safety of coadministering tetanus toxoid, reduced
diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines during
pregnancy by comparing adverse events after concomitant and sequential
vaccination. METHODS: We conducted a retrospective cohort study of pregnant women
aged 14-49 years in the Vaccine Safety Datalink from January 1, 2007, to November
15, 2013. We compared medically attended acute events (fever, any acute reaction)
and adverse birth outcomes (preterm delivery, low birth weight, small for
gestational age) in women receiving concomitant Tdap and influenza vaccination
and women receiving sequential vaccination. RESULTS: Among 36,844 pregnancies in
which Tdap and influenza vaccines were administered, the vaccines were
administered concomitantly in 8,464 (23%) pregnancies and sequentially in 28,380
(77%) pregnancies. Acute adverse events after vaccination were rare. We found no
statistically significant increased risk of fever or any medically attended acute
adverse event in pregnant women vaccinated concomitantly compared with
sequentially. When analyzing women at 20 weeks of gestation or greater during
periods of influenza vaccine administration, there were no differences in preterm
delivery, low-birth-weight, or small-for-gestational-age neonates between women
vaccinated concomitantly compared with sequentially in pregnancy. CONCLUSION:
Concomitant administration of Tdap and influenza vaccines during pregnancy was
not associated with a higher risk of medically attended adverse acute outcomes or
birth outcomes compared with sequential vaccination. LEVEL OF EVIDENCE: II.
PMID- 26444110
TI - Changes in Use of Long-Acting Reversible Contraceptive Methods Among U.S. Women,
2009-2012.
AB - OBJECTIVE: To examine current levels, current correlates of, and changes in long
acting reversible contraceptive (LARC) use, including intrauterine devices and
implants, among females aged 15-44 years using contraception between 2008-2010
and 2011-2013 with specific attention to associations between race, income, and
age and their LARC use. METHODS: We analyzed data from two rounds of the National
Survey of Family Growth, nationally representative samples of females aged 15-44
years, consisting of 6,428 females in 2008-2010 and 5,601 females in 2011-2013.
We conducted simple and multivariable logistic regression analyses with
adjustments for the sampling design to identify demographic characteristics
predictive of LARC use and changes in these patterns between the two time
periods. In this cross-sectional, descriptive study, our primary outcome of
interest was current prevalence of LARC use among all contraceptive users at the
time of the interview. RESULTS: The prevalence of LARC use among contracepting
U.S. females increased from 8.5% in 2009 to 11.6% in 2012 (P<.01). The most
significant increases occurred among Hispanic females (from 8.5% to 15.1%), those
with private insurance (7.1-11.1%), those with fewer than two sexual partners in
the previous year (9.2-12.4%), and those who were nulliparous (2.1-5.9%) (all
P<.01). In multivariable analyses adjusting for key demographic characteristics,
the strongest associations with LARC use in 2012 were parity (adjusted odds
ratios [ORs] 4.3-5.5) and having a history of stopping non-LARC hormonal use
(adjusted OR 1.9). Women aged 35-44 years (adjusted OR 0.3) were less likely to
be LARC users than their counterparts (all P<.001). Poverty status was not
associated with LARC use. There were no differences in discontinuation of LARC
methods resulting from dissatisfaction between minority women and non-Hispanic
white women. CONCLUSION: During the most recent time period surveyed, use of LARC
methods, particularly intrauterine devices, increased almost uniformly across the
population of users. LEVEL OF EVIDENCE: III.
PMID- 26444111
TI - Prior Ultrasound-Indicated Cerclage: Comparison of Cervical Length Screening or
History-Indicated Cerclage in the Next Pregnancy.
AB - OBJECTIVE: To evaluate outcomes of women with prior ultrasound-indicated
cerclage, who in their subsequent pregnancy were either followed by transvaginal
ultrasound cervical length screening or received a planned history-indicated
cerclage. METHODS: Multicenter cohort study of singleton gestations with a prior
ultrasound-indicated cerclage performed from 1994 to 2014. We evaluated three
pregnancies in the study participants: first pregnancy with prior spontaneous
preterm birth at less than 37 weeks of gestation; second pregnancy with
ultrasound-indicated cerclage for cervical length 25 mm or less; and the third
index pregnancy managed with either transvaginal ultrasound cervical length
screening with ultrasound-indicated cerclage for cervical length 25 mm or less or
planned history-indicated cerclage. The primary outcome was incidence of
spontaneous preterm birth at less than 37 weeks of gestation. We planned a
subgroup analysis for women who delivered at less than 32 weeks of gestation
compared with 32 weeks of gestation or greater in their prior ultrasound
indicated cerclage pregnancy. RESULTS: Of 102 singleton gestations included, 38
(37.3%) were followed with transvaginal ultrasound cervical length screening and
64 (62.7%) underwent history-indicated cerclage. Of 38 women in the transvaginal
ultrasound group, 18 (47.4%) underwent ultrasound-indicated cerclage for cervical
length 25 mm or less. After adjusting for confounders, the rate of spontaneous
preterm birth at less than 37 weeks of gestation was similar between transvaginal
ultrasound cervical length screening and history-indicated cerclage groups (36.8%
compared with 43.8%; adjusted odds ratio 0.77, 95% confidence interval 0.47
1.45). Secondary outcomes were also similar in both groups. All women (n=7) who
delivered at less than 32 weeks of gestation in their prior pregnancy and
subsequently had transvaginal ultrasound screening received ultrasound-indicated
cerclage in the index pregnancy compared with only 35.5% of women who delivered
at 32 weeks of gestation or greater in their prior pregnancy. CONCLUSION: Women
with prior ultrasound-indicated cerclage have similar outcomes if they receive
either transvaginal ultrasound cervical length screening with ultrasound
indicated cerclage for cervical length 25 mm or less or planned history-indicated
cerclage in the subsequent pregnancy. Less than 50% of the transvaginal
ultrasound cervical length screening group require a repeat ultrasound-indicated
cerclage in the subsequent pregnancy. LEVEL OF EVIDENCE: II.
PMID- 26444112
TI - Health Care Disparities in Hysterectomy for Gynecologic Cancers: Data From the
2012 National Inpatient Sample.
AB - OBJECTIVE: To examine hysterectomies in the United States performed for
gynecologic malignancies and identify factors associated with the use of
minimally invasive techniques. METHODS: This is a cross-sectional analysis of the
2012 National Inpatient Sample, the largest national all-payer database of
hospital discharges. International Classification of Diseases, 9th Revision,
Clinical Modification codes for any type of hysterectomy performed for
gynecologic malignancy were used to abstract pertinent observations. Weighted
multivariable logistic regression models were used to examine the associations
between demographic and clinical factors and mode of hysterectomy by cancer
diagnosis. RESULTS: In 2012, there were an estimated 46,450 hysterectomies for
gynecologic malignancy in the United States. Of these, 28,285 (61%) were
performed for uterine, 4,275 (9%) for cervical, 12,370 (27%) for ovarian cancer,
and 1,520 (3%) for other gynecologic malignancies. Minimally invasive
hysterectomy was used in 50% of uterine, 43% of cervical, and 8.5% of ovarian
cancer cases. Black women had decreased odds of undergoing minimally invasive
hysterectomy for uterine (adjusted odds ratio [OR] 0.50, 95% confidence interval
[CI] 0.40-0.0.63, P<.001) and cervical (adjusted OR 0.56, 95% CI 0.33-0.96,
P=.03) cancers. Those without insurance or with Medicaid had decreased odds of
undergoing minimally invasive hysterectomy (P<.001) for uterine cancer. As
compared with the Northeast, patients in the South (adjusted OR 0.72, 95% CI 0.53
0.98, P=.04) were less likely to undergo minimally invasive hysterectomy for
uterine cancer, whereas those in the West more likely (adjusted OR 1.48, 95% CI
1.10-1.99, P=.009). CONCLUSION: Minimally invasive hysterectomy for gynecologic
malignancies remained underused in 2012; there were striking racial disparities
associated with use of minimally invasive hysterectomy for uterine and cervical
cancers. LEVEL OF EVIDENCE: III.
PMID- 26444113
TI - Heterogeneity in Blood Product Acceptance Among Antenatal Patients of the
Jehovah's Witness Faith.
AB - OBJECTIVE: To understand the antepartum attitudes toward blood product
transfusion among members of the Jehovah's Witness faith. METHODS: We performed a
retrospective study using antenatal consultation notes of Jehovah's Witness
patients from the bloodless medicine program at a regional tertiary care
maternity hospital over a 4-year period to determine their blood transfusion
preferences. RESULTS: Eighty-seven consultations were performed. The median age
of women undergoing consultation was 27 years (range 14-39 years), and most were
either African American (48/87 [55.2%]; 95% confidence interval [CI] 44.8-65.7)
or Caucasian (35/87 [40.2%]; 95% CI 29.9-50.5). The mean+/-standard deviation
antenatal hemoglobin concentration was 11.9+/-1.4 g/dL (n=57). Although all 87
women stated that they would not accept conventional blood products such as red
blood cells, plasma, or platelets, 55 of 87 (63.2%; 95% CI 53.1-73.3) stated that
they would accept all of the recombinant or fractionated blood products including
cryoprecipitate. Stated acceptance of fractionated or recombinant products did
not vary by parity, race, or age. A further 23 of 87 (26.4%; 95% CI 17.1-35.7)
women stated they would accept some but not all of the fractionated or
recombinant blood products, whereas 9 of 87 (10.3%; 95% CI 3.9-16.7) stated they
would not accept any of these products. CONCLUSION: In the antenatal period,
Jehovah's Witness women have variable attitudes toward receipt of blood products.
A discussion with each patient is essential to understand whether and which blood
products may be used when indicated.
PMID- 26444114
TI - A Proactive Approach to Neonates Born at 23 Weeks of Gestation.
AB - OBJECTIVE: To evaluate in-hospital survival, survival without major morbidity,
and neurodevelopmental impairment for neonates born at 23 weeks of gestation
provided proactive, coordinated, and comprehensive perinatal and neonatal
management. METHODS: This was a retrospective cohort study conducted at a single,
tertiary care center between 2004 and 2013. Enrollment was limited to mother
neonate dyads at 23 weeks of gestation who were provided a proactive approach
defined as documented evidence of antenatal corticosteroid administration,
willingness to provide cesarean delivery for fetal distress, and neonatal
resuscitation and intensive care. Among survivors, major morbidities
(predischarge) and neurodevelopmental assessments at corrected ages of 18-22
months were examined. RESULTS: Among 152 live births identified, 101 neonates
received proactive care, of whom 60 (59%) survived to hospital discharge. Preterm
premature rupture of membranes (adjusted odds ratio [OR] 0.29, 95% confidence
interval [CI] 0.09-0.94), fetal growth restriction (OR 0.16, 95% CI 0.03-0.89),
delivery room cardiopulmonary resuscitation (OR 0.07, 95% CI 0.02-0.32), and
prolonged intubation sequence (OR 0.15, 95% CI 0.05-0.45) were associated with
lower neonatal survival. Among neonatal intensive care unit survivors, 62% had at
least one major morbidity. Among 50 survivors with assessment at 18-22 months,
six (12%) were unimpaired, 20 (40%) had mild impairment, and 24 (48%) had
moderate or severe neurodevelopmental impairment. CONCLUSION: Proactive,
interdisciplinary care enabled more than half of the neonates born at 23 weeks of
gestation to survive, and approximately half of children evaluated at 18 months
exhibited no or mild impairment. This information should be considered when
providing prognostic advice to families with threatened preterm birth at 23 weeks
of gestation. LEVEL OF EVIDENCE: II.
PMID- 26444115
TI - Tocolysis for Women With Early Spontaneous Preterm Labor and Advanced Cervical
Dilation.
AB - OBJECTIVE: To characterize tocolytic use and examine perinatal outcomes among
women presenting very preterm with spontaneous labor and cervical dilation 4 cm
or greater. METHODS: This was a retrospective cohort study. Data from January
2000 to June 2011 in a single health care system were reviewed. Women with
singleton, nonanomalous fetuses and preterm labor with intact membranes between
23 and 32 weeks of gestation who had cervical dilation 4 cm or greater and less
than 8 cm at admission were included. Women receiving one or more tocolytics
(magnesium sulfate, indomethacin, or nifedipine) were compared with those who did
not receive tocolysis. The primary outcome was composite major neonatal
morbidity. RESULTS: Two hundred ninety-seven women were included; 233 (78.5%)
received at least one tocolytic. Women receiving tocolysis were slightly less
dilated (median 5 compared with 6 cm, P<.001) at presentation and were more
likely to receive at least a partial course of corticosteroids (88.4% compared
with 56.3%, P<.001). Initial composite severe neonatal morbidity rates were
similar (41.6% compared with 43.8%, P=.761) regardless of tocolytic
administration. Those receiving tocolysis were significantly more likely to be
pregnant at least 48 hours after admission (23.6% compared with 7.8%, P=.005),
but a similar proportion delivered within 7 days of admission (94.8% compared
with 95.3%, P>.99), and delivery gestational ages were similar (28.9 compared
with 29.2 weeks, P=.408). The incidence of chorioamnionitis and postpartum
endometritis was similar between groups. CONCLUSION: The majority of women
presenting very preterm with advanced cervical dilation received tocolysis.
Although tocolysis administration increased the likelihood of achieving at least
48 hours of latency, initial neonatal outcomes were similar. LEVEL OF EVIDENCE:
II.
PMID- 26444116
TI - The Relationship Between Intertwin Membrane Separation and Pregnancy Outcome.
AB - OBJECTIVE: To evaluate the association of intertwin membrane separation and
pregnancy outcome. METHODS: This is a retrospective cohort study of women with
dichorionic twins who were diagnosed with spontaneous intertwin membrane
separation between 2004 and 2013 at a large tertiary care maternity hospital.
Control participants were selected as the next two sets of dichorionic twins that
delivered at the study institution after a case participant delivered and that
did not have an intrauterine procedure. Maternal, fetal, and delivery
characteristics were compared using Wilcoxon rank-sum tests. Logistic regressions
were used to assess the association of membrane separation and preterm delivery.
RESULTS: Among the 27 cases of spontaneous intertwin membrane separation, the
median gestational age at diagnosis was 28 weeks (interquartile range 25.5-28.8)
and the median gestational age at delivery was 37 weeks (interquartile range 35.3
37.0). The rate of preterm delivery, our primary outcome, was 48% for the case
group and 76% for the control group (odds ratio [OR] 0.29, P=.01). The rate of
spontaneous preterm delivery was also lower for the case group (19% compared with
44%; OR 0.25, P=.26) as was the rate of neonatal intensive care unit admission
(37% compared with 61%; OR 0.37, P=.04). CONCLUSION: Our retrospective cohort
study demonstrates that intertwin membrane separation is not associated with
adverse outcomes in dichorionic twin pregnancies. Thus, it is reasonable to
manage these pregnancies expectantly. LEVEL OF EVIDENCE: II.
PMID- 26444117
TI - Cross-Cultural Obstetric and Gynecologic Care of Muslim Patients.
AB - With the growing number of Muslim patients in the United States, there is a
greater need for obstetrician-gynecologists (ob-gyns) to understand the health
care needs and values of this population to optimize patient rapport, provide
high-quality reproductive care, and minimize health care disparities. The few
studies that have explored Muslim women's health needs in the United States show
that among the barriers Muslim women face in accessing health care services is
the failure of health care providers to understand and accommodate their beliefs
and customs. This article outlines health care practices and cultural competency
tools relevant to modern obstetric and gynecologic care of Muslim patients,
incorporating emerging data. There is an exploration of the diversity of opinion,
practice, and cultural traditions among Muslims, which can be challenging for the
ob-gyn who seeks to provide culturally competent care while attempting to avoid
relying on cultural or religious stereotypes. This commentary also focuses on
issues that might arise in the obstetric and gynecologic care of Muslim women,
including the patient-physician relationship, modesty and interactions with male
health care providers, sexual health, contraception, abortion, infertility, and
intrapartum and postpartum care. Understanding the health care needs and values
of Muslims in the United States may give physicians the tools necessary to better
deliver high-quality care to this minority population.
PMID- 26444118
TI - Physician Needs Help Stat in Room 3.
PMID- 26444119
TI - Beyond Coercion: Let Us Grapple With Bias.
PMID- 26444120
TI - Connect the Dots....
PMID- 26444121
TI - What Is New in Pelvic Organ Prolapse?: Best Articles From the Past Year.
AB - This month we focus on current research in pelvic organ prolapse. Dr. Kenton
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- 26444122
TI - Disseminated Intravascular Coagulation Syndromes in Obstetrics.
AB - Disseminated intravascular coagulation (DIC) is a syndrome that can be initiated
by a myriad of medical, surgical, and obstetric disorders. Also known as
consumptive coagulopathy, DIC is a common contributor to maternal morbidity and
mortality and is associated with up to 25% of maternal deaths. The
etiopathogenesis of DIC is complex and currently thought to be initiated by
tissue factor or thromboplastin, which is released from trophoblastic or fetal
tissue, or maternal decidua or endothelium. Tissue factor activates the
coagulation sequence to cause fibrin clotting and its dissolution by the
fibrinolysin system. The result of this process can range from mild, clinically
insignificant laboratory derangements to marked coagulopathy with bleeding at
sites of minimal trauma. Although clinical recognition varies by disease
severity, several organizations have attempted to standardize the diagnosis
through development of scoring systems. Several important--albeit not necessarily
common--obstetric disorders associated with DIC include placental abruption,
amniotic fluid embolism, sepsis syndrome, and acute fatty liver of pregnancy.
More common disorders include severe preeclampsia, hemolysis, elevated liver
enzymes, and low platelet count syndrome, and massive obstetric hemorrhage.
Importantly, many of these disorders either cause or are associated with
substantive obstetric hemorrhage. Treatment of DIC is centered on two principles.
The first is identification and treatment of the underlying disorder. Because
many women with consumptive coagulopathy also have massive hemorrhage, the second
tenet of treatment is that obstetric complications such as uterine atony or
lacerations must be controlled simultaneously with prompt blood and component
replacement for a salutary outcome.
PMID- 26444124
TI - Removal of a Nonpalpable Etonogestrel Implant With Preprocedure Ultrasonography
and Modified Vasectomy Clamp.
AB - BACKGROUND: Deep etonogestrel contraceptive implant placements still occur
despite design modifications to the implant inserter. We present a method for
outpatient removal of a nonpalpable etonogestrel implant using preprocedure
ultrasonography for implant localization followed by removal with a modified
vasectomy clamp, a modification of the "U" technique for six-capsule
levonorgestrel implant removal. TECHNIQUE: In women with a nonpalpable
etonogestrel implant containing barium sulfate, we obtain a radiographic
examination to confirm the implant's presence in the upper extremity. Using an 18
MHz linear ultrasound transducer, we identify and mark the implant location on
the patient's arm, noting the depth. We remove the implant with local anesthesia
in the office using a modified vasectomy clamp through a 5-mm or less skin
incision directly over the implant. EXPERIENCE: All three patients referred to
our office with nonpalpable etonogestrel implants had successful removal using
this technique. CONCLUSION: Nonpalpable contraceptive implants can be removed in
the office using a modified vasectomy clamp after localization with high
frequency ultrasonography. Given the relative infrequency of nonpalpable implant
removals, regional expert sites with health care providers experienced in
difficult removals should be created for patient referrals.
PMID- 26444123
TI - Pregnancy Outcomes Among Obese Women and Their Offspring by Attempted Mode of
Delivery.
AB - OBJECTIVE: To compare maternal and neonatal morbidities among obese women and
their offspring by attempted delivery approach. METHODS: We performed a
retrospective cohort study of 47,372 obese women at delivery (body mass index 30
or greater) eligible for vaginal delivery who were carrying singleton vertex
fetuses at 37 weeks of gestation or greater. Prior cesarean delivery, congenital
anomalies, and antepartum stillbirth were exclusion criteria. We analyzed
outcomes by attempted delivery route and stratified by parity. The composite
maternal outcome included intensive care admission, death, hemorrhage,
transfusion, or thromboembolism. The neonatal composite included intensive care
unit admission, death, seizure, ventilator use, birth injury, or asphyxia.
Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were calculated
using Poisson regression. RESULTS: Among nulliparous women attempting vaginal
delivery (n=15,268), the success rate was 72.6% and among parous women
(n=23,426), it was 93.7%. The maternal composite outcome rate was not
statistically higher among nulliparous women (7.7% compared with 4.2% [adjusted
RR 1.58, 95% CI 0.96-2.59]) but it was among parous women (7.6% compared with
2.5% [adjusted RR 2.45, 95% CI 1.23-4.90]) attempting vaginal delivery related to
hemorrhage, blood transfusion, or both. In contrast, the neonatal composite
outcome rate was lower in parous women (6.0% compared with 11.6% [adjusted RR
0.65, 95% CI 0.51-0.83]) but not in nulliparous women (10.2% compared with 12.4%
[adjusted RR 0.91, 95% CI 0.74-1.12]) parous. CONCLUSION: In obese nulliparous
women, attempted vaginal delivery was not associated with increased composite
maternal or neonatal morbidity. In obese parous women, attempted vaginal delivery
was associated with increased composite maternal morbidity and lower composite
neonatal morbidity. LEVEL OF EVIDENCE: II.
PMID- 26444125
TI - Short-Term and Long-Term Postnatal Outcomes of Expectant Management After
Previable Preterm Premature Rupture of Membranes With and Without Persistent
Oligohydramnios.
AB - OBJECTIVE: To compare postnatal outcomes in pregnancies managed expectantly after
previable preterm premature rupture of membranes (PROM) in relation to amniotic
fluid volume. METHODS: A retrospective cohort study was performed in 92 women
with amniotic fluid leakage for more than a week after previable preterm PROM
(gestational age 14 1/7-24 0/7 weeks) who delivered a liveborn neonate at or
after 24 1/7 weeks of gestation from 2002 to 2014. Short-term (sepsis,
intracerebral hemorrhage, retinopathy of prematurity, respiratory distress
syndrome, bronchopulmonary dysplasia) and long-term (cerebral palsy and
developmental delay) outcomes were compared between women with (n=58) and without
persistent oligohydramnios (n=34), defined as maximal vertical pocket less than 2
cm or amniotic fluid index less than 5 cm. We analyzed discrete data using the
chi2 or Fisher's exact test and continuous variables using Student's t test or
Mann-Whitney U test. We also performed multivariable analyses. RESULTS: There was
a significant difference in survival rate at discharge (44/58 [75.9%] compared
with 34/34 [100%], P=.001) and developmental delay at a median age of 4 years
after performing multiple regression analysis (adjusted odds ratio [OR] 70.3, 95%
confidence interval [CI] 2.9-1,719.9, P=.009) between participants with
persistent oligohydramnios and participants with normal amniotic fluid volume. A
multiple regression analysis, performed to control for confounders, revealed that
gestational age at delivery (adjusted OR 0.3, 95% CI 0.1-0.7, P=.008) and breech
presentation (adjusted OR 90.8, 95% CI 2.2-3,778.1, P=.018) were significant
factors affecting survival of children with persistent oligohydramnios.
CONCLUSION: The postnatal survival rate after previable preterm PROM was lower
and developmental delay more frequent in participants with persistent
oligohydramnios than in participants with normal amniotic fluid volume. Even so,
most neonates born alive after previable preterm PROM and persistent
oligohydramnios survived to discharge and were developmentally normal. The
overall survival rate was higher than in previous studies. LEVEL OF EVIDENCE: II.
PMID- 26444126
TI - Racial and Ethnic Disparities in Hospital Readmissions After Delivery.
AB - OBJECTIVE: To examine 30-day readmission rates after vaginal and cesarean
delivery by race-ethnicity and insurance status. METHODS: We analyzed hospital
discharge data contained in a statewide database maintained by the Connecticut
Department of Public Health. Discharge data for patients admitted for vaginal
delivery without complication (n=167,857) and cesarean delivery without
complication (n=75,552) from 2005 to 2012 were analyzed using marginal logistic
models for clustered data with generalized estimating equations. RESULTS: Results
from logistic models indicated that 30-day readmission rates per 1,000 patients
were significantly higher among black (28.9/1,000; confidence interval [CI] 25.5
32.7) and Hispanic women (21.4/1,000; CI 18.9-24.2) than among white women
(12.9/1,000; CI 11.9-14.0) after cesarean delivery. Similarly higher rates of
readmission were observed for black (14.6/1,000; CI 13.0-16.5) and Hispanic women
(10.7/1,000; CI 9.6-12.0) relative to white women (7.5/1,000; CI 7.0-8.1) after
vaginal delivery. Rates of 30-day readmission were significantly higher (odds
ratio 1.27-1.30) among those covered by Medicaid. Controlling for patient
socioeconomic status, comorbidities, and payer did not substantially reduce race
and ethic differences in the odds of readmission. CONCLUSION: Significant racial
and ethnic disparities in readmissions were observed for procedures related to
childbirth using a statewide database capturing all payers across all acute care
hospital settings. Compared with white women, black women were twice as likely
and Hispanic women 40-50% more likely to be readmitted within 30 days of vaginal
or cesarean delivery. LEVEL OF EVIDENCE: II.
PMID- 26444127
TI - Intrauterine Contraception Among Women Living With Human Immunodeficiency Virus:
A Randomized Controlled Trial.
AB - OBJECTIVE: To compare discontinuation rates of the levonorgestrel and copper
intrauterine devices (IUDs) among women with human immunodeficiency virus.
METHODS: A double-masked randomized trial was conducted at Mulago Hospital,
Uganda. Women received either a copper or levonorgestrel IUD. The primary outcome
was discontinuation of intrauterine contraception within 1 year of placement. The
secondary outcomes were incidence of side effects and severe adverse events. To
discern a difference of 10% from a copper IUD discontinuation rate of 18%, power
of 80%, and 95% confidence interval (CI), a sample size of 351 per arm was
estimated. Analysis of the primary outcome was by intension-to-treat principle.
RESULTS: From September 2013 to December 2014, 979 were screened and 703
randomized as follows: 349 to the copper group and 354 to the levonorgestrel
group. In total, 8.6% (29/338) women in the copper group compared with 8.1%
(27/334) in the levonorgestrel group discontinued intrauterine conception within
1 year of placement (incidence rate ratio 1.1 [95% CI 0.64-1.96]). Overall, the
incidence of heavy bleeding was higher in the copper group (37% [125/338]) than
in the levonorgestrel group (19.5% [65/334]). However, the incidence of
amenorrhea, which occurred in 3.3% (11/338) of women, was lower in the copper
group than the 19.8% (66/334) of women who reported amenorrhea in the
levonorgestrel group. CONCLUSION: There was no difference in discontinuation
rates between the copper and levonorgestrel devices. Women in the levonorgestrel
group had reduced incidence of heavy bleeding and a higher incidence of
amenorrhea compared with those in the copper group. CLINICAL TRIAL REGISTRATION:
Pan African Clinical Trial Registry, www.pactr.org, PACTR 201308000561212. LEVEL
OF EVIDENCE: I.
PMID- 26444128
TI - Precesarean Prophylactic Balloon Catheters for Suspected Placenta Accreta: A
Randomized Controlled Trial.
AB - OBJECTIVE: To examine the effect of prophylactic balloon catheters on bleeding
morbidity among women with a prenatal diagnosis of placenta accreta. METHODS: In
a randomized trial, women with a prenatal diagnosis of placenta accreta were
randomized to either preoperative prophylactic balloon catheters (intervention
group) or to a control group. Other than placement of the prophylactic balloon
catheters in the anterior division of the internal iliac arteries, the same
multidisciplinary approach was used in both groups. The primary study outcome was
the number of packed red blood cell (RBC) units transfused. To detect a mean
reduction of three packed RBC units with the prophylactic balloon catheters, 12
women in each group were needed. RESULTS: Between January 2009 and March 2015, 27
women were randomized: 13 in the intervention group and 14 in the control group.
Demographic and obstetric characteristics were similar between the groups. Six
(46.2%) women in the intervention and seven (50.0%) in the control group
underwent cesarean hysterectomy (P=.84). There were no significant differences
between the intervention and control groups in the mean number of packed RBC
units transfused, 5.2 (+/-6.2) and 4.1 (+/-3.8), respectively (P=.90), or in the
calculated blood loss, 4,950 (+/-5,051) and 4,709 (+/-3,434) mL (P=.72). The
number of women with blood loss greater than 2,500 mL, number of plasma products
transfused, duration of surgery, peripartum complications, and hospitalization
length did not differ significantly between the groups. Reversible adverse
effects related probably to prophylactic balloon catheter insertion were noted in
2 of 13 (15.4%) women. CONCLUSION: In women with preoperative suspicion of
placenta accreta, preoperative placement of prophylactic balloon catheters did
not affect the number of packed RBC units transfused. CLINICAL TRIAL
REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01373255. LEVEL OF
EVIDENCE: I.
PMID- 26444129
TI - Large-for-Gestational-Age Ultrasound Diagnosis and Risk for Cesarean Delivery in
Women With Gestational Diabetes Mellitus.
AB - OBJECTIVE: To assess the accuracy of a large-for-gestational-age (LGA) ultrasound
diagnosis and the subsequent risk for cesarean delivery associated with
ultrasound diagnosis of LGA among women with gestational diabetes mellitus.
METHODS: This was a retrospective cohort study of 903 women with GDM who
delivered after 36 weeks of gestation with an ultrasound-estimated fetal weight
within 31 days of delivery. Delivery outcomes were compared between women with an
ultrasound diagnosis of LGA and a non-LGA ultrasound diagnosis. RESULTS: Based on
ultrasound assessments, we identified 248 women with an LGA fetus and 655 women
with a non-LGA fetus. Among women with an LGA ultrasound diagnosis, 56 of 248
(22.6%) delivered an LGA neonate, whereas, of women with a non-LGA ultrasound
diagnosis, 18 of 655 (2.8%) delivered an LGA neonate. Ultrasound diagnosis of LGA
was associated with increased risk for cesarean delivery (adjusted odds ratio
[OR] 3.13, 95% confidence interval [CI] 2.10-4.67, P<.001) after adjusting for
relevant covariates. Stratified analyses demonstrated that ultrasound diagnosis
of LGA was associated with an increased risk for cesarean delivery whether the
birth weight was between 2,500 and 3,499 g (OR 2.82, 95% CI 1.62-4.84, P<.001) or
between 3,500 and 4,500 g (OR 3.47, 95% CI 2.06-5.88, P<.001). CONCLUSION:
Ultrasonography significantly overestimates the prevalence of LGA in women with
gestational diabetes mellitus, and an ultrasound diagnosis of LGA is associated
with an increased risk for cesarean delivery independent of birth weight. LEVEL
OF EVIDENCE: II.
PMID- 26444130
TI - Enhancing Participation in Depression Care in Outpatient Perinatal Care Settings:
A Systematic Review.
AB - OBJECTIVE: To examine a wide range of study designs and outcomes to estimate the
extent to which interventions in outpatient perinatal care settings are
associated with an increase in the uptake of depression care. DATA SOURCES:
PubMed, CINAHL, PsycINFO, ClinicalTrials.gov, and Scopus (EMBASE) were searched
for studies published between 1999 and 2014 that evaluated mental health care use
after screening for depression in perinatal care settings. METHODS OF STUDY
SELECTION: Inclusion criteria were: 1) English language; 2) pregnant and
postpartum women who screened positive for depression; 3) exposure (validated
depression screening in outpatient perinatal care setting); and, 4) outcome
(mental health care use). Searches yielded 392 articles, 42 met criteria for full
text review, and 17 met inclusion criteria. Study quality was assessed using a
modified Downs and Black scale. TABULATION, INTEGRATION, AND RESULTS: Articles
were independently reviewed by two abstractors and consensus reached. Study
design, intervention components, and mental health care use were defined and
categorized. Seventeen articles representing a range of study designs, including
one randomized controlled trial and one cluster randomized controlled trial, were
included. The average quality rating was 61% (31.0-90.0%). When no intervention
was in place, an average of 22% (13.8-33.0%) of women who screened positive for
depression had at least one mental health visit. The average rate of mental
health care use was associated with a doubling of this rate with patient
engagement strategies (44%, 29.0-90.0%), on-site assessments (49%, 25.2-90.0%),
and perinatal care provider training (54%, 1.0-90.0%). High rates of mental
health care use (81%, 72.0-90.0%) were associated with implementation of
additional interventions, including resource provision to women, perinatal care
provider training, on-site assessment, and access to mental health consultation
for perinatal care providers. CONCLUSION: Screening alone was associated with 22%
mental health care use among women who screened positive for depression; however,
implementation of additional interventions was associated with a two to fourfold
increased use of mental health care. Although definitive studies are still
needed, screening done in conjunction with interventions that target patient,
health care provider, and practice-level barriers is associated with increased
improved rates of depression detection, assessment, referral, and treatment in
perinatal care settings.
PMID- 26444131
TI - Quantification of Heteroaggregation between Citrate-Stabilized Gold Nanoparticles
and Hematite Colloids.
AB - Collisions with and attachment to natural colloids (heteroaggregation) is likely
to influence significantly the fate, transport, and toxicity of engineered
nanoparticles (ENPs). This study investigated heteroaggregation between hematite
(alpha-Fe2O3) colloids and citrate-capped gold nanoparticles (Cit-AuNPs) using a
novel approach involving time-resolved dynamic light scattering and parallel
experiments designed to quantify nanoparticle attachment and heteroaggregate
surface charge. Experiments were performed in low ionic strength synthetic water
at environmentally relevant pH in the presence and absence of Suwannee River
Natural Organic Matter (SRNOM). In the absence of SRNOM at pH values where Cit
AuNPs and hematite are oppositely charged, attachment efficiencies are high and
Cit-AuNPs are capable of destabilizing hematite following an "electrostatic
patch" mechanism. Furthermore, maximum observed surface coverages were far below
those predicted by geometry alone, a fact predicted by the random sequential
adsorption (RSA) model that has significant implications for the estimation of
heteroaggregate attachment efficiencies. At pH values where both particles are
negative or in the presence of small amounts of SRNOM, attachment was minimal.
Calculated attachment efficiencies using the measured surface coverages
corroborate these findings. The calculation of attachment efficiencies and the
identification of mechanisms governing heteroaggregation represents an important
step toward predicting the transport, fate, and toxicity of ENPs in the
environment.
PMID- 26444132
TI - Disowning the self: The cultural value of modesty can attenuate self-positivity.
AB - Western participants endorse a higher number of positive traits as self
descriptive, but endorse a lower number of negative traits as self-descriptive.
They also respond quicker to categorize positive traits as self-descriptive, but
respond slower to categorize negative traits as self-descriptive. Is this self
positivity bias qualified by the cultural value of modesty? We induced modesty
(vs. punctuality) and assessed self-descriptiveness judgments and response times
among Chinese participants. We replicated the self-positivity bias in regards to
both self-descriptiveness judgments and response times. In the case of self
descriptiveness judgments, however, the bias was partially qualified by modesty.
Relative to control participants, those in the modesty condition endorsed fewer
positive traits as self-descriptive and manifested a tendency toward endorsing
more negative traits as self-descriptive. In the case of response times, the self
positivity bias was unqualified by modesty. Within both conditions, participants
were quicker to categorize positive traits as self-descriptive and were slower to
categorize negative traits as self-descriptive. The results speak to the relation
between the self-positivity bias and the self-reference effect and illustrate the
malleability of self-processing.
PMID- 26444133
TI - The role of emotions in the reduction of HIV/AIDS stigma among physicians in
training.
AB - Scientific literature has systematically documented the negative effects of
social stigma for people living with HIV/AIDS (PLWHA). HIV/AIDS stigma has the
potential to negatively impact self-care strategies for those already affected,
and simultaneously hinder prevention efforts to deter the emergence of new
infections. When health professionals manifest these negative attitudes access to
quality health-care and prevention strategies can be seriously affected.
Scientifically tested interventions to reduce HIV/AIDS stigma among health
professionals are still scarce. Although the number of tested interventions has
increased over the past decade, few of them target Latino health professionals or
Spanish-speaking populations. Furthermore, although some of those interventions
have been reported as effective for stigma reduction, more work is needed to
better understand the underlying variables that account for the reduction of
stigma attitudes in those efforts. The SPACES intervention has been documented as
an effective HIV/AIDS stigma-reduction intervention focusing on health-care
professionals in training. The intervention, which is delivered in Spanish, has
been previously tested with medical students in Puerto Rico and shown significant
results in addressing negative attitudes toward PLWHA. The main objective of this
study was to document the underlying variables that fostered reduction of
HIV/AIDS stigma due to participation in the SPACES intervention. Results evidence
that health professionals in training who participated in the intervention (n =
507) had less stigmatizing attitudes toward PLWHA due to an increase in their
positive emotions toward this population. In light of these results, we discuss
the importance of engaging health professionals in HIV/AIDS stigma-reduction
interventions that go beyond the provision of information and skills for
interacting with PLWHA, and address the emotional component of HIV/AIDS stigma.
PMID- 26444134
TI - [What is Important for Diagnosis and Therapy Follow-up in Chronic Cough?].
AB - Within the last years there has been significant progress in the field of chronic
cough. So far, the analysis and evaluation of chronic cough was done mainly on
the basis of subjective methods such as manual counts of cough events,
questionnaires and diaries. Testing cough hypersensitivity and monitoring 24 h
cough represent objective criteria. Validated questionnaires on cough frequency
and quality of life represent the impact of chronic cough. Cough frequency
monitoring, the preferred tool to objectively assess cough, should be used as
primary end-point in clinical trials. It will also be possible to discriminate
between productive and non-productive cough. The relationship with subjective
measures of cough is weak. In the future, cough and its therapy should therefore
be assessed with a combination of subjective and objective tools.
PMID- 26444136
TI - [Idiopathic Pulmonary Fibrosis].
AB - Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial
pneumonia and a disease of the elderly. Cigarette smoking and longterm exposure
to substances harming alveolar epithelial cells are risk factors for the
development of IPF. There is also evidence for a genetic susceptibility. IPF is
defined as the idiopathic variant of Usual Interstitial Pneumonitis (UIP).
Diagnosis of IPF is complex and based on the exclusion of other diseases
associated with an UIP pattern. The only cure is lung transplantation. In the
last years there was a breakthrough in the treatment of IPF. With pirfenidone and
nintedanib there are now two compounds approved for the treatment of IPF.
PMID- 26444135
TI - S2k-Guideline "Prolonged Weaning".
AB - All mechanically ventilated patients must be weaned from the ventilator at some
stage. According to an International Consensus Conference the criteria for
"prolonged weaning" are fulfilled if patients fail at least 3 weaning attempts
(i. e. spontaneous breathing trial, SBT) or require more than 7 days of weaning
after the first SBT. This occurs in about 15 - 20 % of patients.Because of the
growing number of patients requiring prolonged weaning a German guideline on
prolonged weaning has been developed. It is an initiative of the German
Respiratory Society (Deutsche Gesellschaft fur Pneumologie und Beatmungsmedizin
e. V., DGP) in cooperation with other societies (see acknowledgement) engaged in
the field chaired by the Association of Scientific and Medical Societies in
Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen
Fachgesellschaften, AWMF).This guideline deals with the definition, epidemiology,
weaning categories, underlying pathophysiology, therapeutic strategies, the
weaning unit, transition to out-of-hospital ventilation and therapeutic
recommendations for end of life care. This short version summarises
recommendations on prolonged weaning from the German guideline.
PMID- 26444137
TI - The role of respiratory measures to assess mental load in pilot selection.
AB - While cardiovascular measures have a long tradition of being used to determine
operator load, responsiveness of the respiratory system to mental load has rarely
been investigated. In this study, we assessed basic and variability measures of
respiration rate (RR), partial pressure of end-tidal carbon dioxide (petCO2) as
well as performance measures in 63 male pilot candidates during completion of a
complex cognitive task and subsequent recovery. Mental load was associated with
an increase in RR and a decrease in respiratory variability. A significant
decrease was also found for petCO2. RR and respiratory variability showed partial
and complete effects of recovery, respectively, whereas petCO2 did not return to
baseline level. Overall, a good performance was related to a stronger reactivity
in RR. Our findings suggest that respiratory parameters would be a useful
supplement to common measures for the assessment of mental load in pilot
selection. Practitioner Summary: Respiratory measures are a promising yet poorly
investigated approach to monitor operator load. For pilot selection, we assessed
respiration in response to multitasking in 63 candidates. Task-related changes as
well as covariation with performance strongly support the consideration of
respiratory parameters when evaluating reactivity to mental load.
PMID- 26444138
TI - ?
PMID- 26444139
TI - ?
PMID- 26444140
TI - ?
PMID- 26444141
TI - ?
PMID- 26444142
TI - Slowed atrial and atrioventricular conduction and depressed HRV in a murine model
of hypertrophic cardiomyopathy.
AB - Hypertrophic cardiomyopathy (HCM) is a common heritable cardiac disorder with
diverse clinical outcomes including sudden death, heart failure, and stroke.
Depressed heart rate variability (HRV), a measure of cardiac autonomic
regulation, has been shown to predict mortality in patients with cardiovascular
disease. Cardiac autonomic remodelling in animal models of HCM are not well
characterised. This study analysed Gly203Ser cardiac troponin-I transgenic (TG)
male mice previously demonstrated to develop hallmarks of HCM by age 21 weeks. 33
mice aged 30 and 50 weeks underwent continuous electrocardiogram (ECG) recording
for 30 min under anaesthesia. TG mice demonstrated prolonged P-wave duration (P <
0.001) and PR intervals (P < 0.001) compared to controls. Additionally, TG mice
demonstrated depressed standard deviation of RR intervals (SDRR; P < 0.01),
coefficient of variation of RR intervals (CVRR; P < 0.001) and standard deviation
of heart rate (SDHR; P < 0.001) compared to controls. Additionally, total power
was significantly reduced in TG mice (P < 0.05). No significant age-related
difference in either strain was observed in ECG or HRV parameters. Mice with HCM
developed slowed atrial and atrioventricular conduction and depressed HRV. These
changes were conserved with increasing age. This finding may be indicative of
atrial and ventricular hypertrophy or dysfunction, and perhaps an indication of
worse clinical outcome in heart failure progression in HCM patients.
PMID- 26444143
TI - Introduction of a closed-system cell processor for red blood cell washing:
postimplementation monitoring of safety and efficacy.
AB - BACKGROUND: After introduction of a closed-system cell processor, the effect of
this product change on safety, efficacy, and utilization of washed red blood
cells (RBCs) was assessed. STUDY DESIGN AND METHODS: This study was a pre
/postimplementation observational study. Efficacy data were collected from
sequentially transfused washed RBCs received as prophylactic therapy by beta
thalassemia patients during a 3-month period before and after implementation of
the Haemonetics ACP 215 closed-system processor. Before implementation, an open
system (TerumoBCT COBE 2991) was used to wash RBCs. The primary endpoint for
efficacy was a change in hemoglobin (Hb) concentration corrected for the duration
between transfusions. The primary endpoint for safety was the frequency of
adverse transfusion reactions (ATRs) in all washed RBCs provided by Canadian
Blood Services to the transfusion service for 12 months before and after
implementation. RESULTS: Data were analyzed from more than 300 RBCs transfused to
31 recipients before implementation and 29 recipients after implementation. The
number of units transfused per episode reduced significantly after
implementation, from a mean of 3.5 units to a mean of 3.1 units (p < 0.005). The
corrected change in Hb concentration was not significantly different before and
after implementation. ATRs occurred in 0.15% of transfusions both before and
after implementation. CONCLUSION: Safety and efficacy of washed RBCs were not
affected after introduction of a closed-system cell processor. The ACP 215
allowed for an extended expiry time, improving inventory management and overall
utilization of washed RBCs. Transfusion of fewer RBCs per episode reduced
exposure of recipients to allogeneic blood products while maintaining efficacy.
PMID- 26444144
TI - Combined use of cyclofructans and an amino acid ester-based ionic liquid for the
enantioseparation of huperzine A and coumarin derivatives in CE.
AB - Cyclofructans (CFs) and their derivatives have recently been proven to be
efficient chiral selectors (CSs) for the enantioseparation of several analytes in
CE, HPLC, and GC. In this study, the chiral separation ability of a number of
native and derivatized CFs was examined in CE. Particularly, six different CFs,
with different derivatization groups and cavity sizes [native CF-6 and CF-7,
isopropyl cyclofructan-6 (IPCF-6), IPCF-7, sulfated cyclofructan-6 (SCF-6), and
SCF-7] were used as CSs for the enantioseparation of huperzine A, warfarin, and
coumachlor. Almost all of the examined CFs, except from SCF-6 & -7, demonstrated
relatively low and sometimes no chiral separation ability for huperzine A. In an
effort to improve both resolution and efficiency, the chiral ionic liquid D
Alanine tert butyl ester lactate (D-AlaC4Lac) was added into the BGE. In most of
the cases, the combination of CF with D-AlaC4Lac resulted in an improvement in
peak efficiency and/or resolution. When CF-6 was utilized with D-AlaC4Lac, a
resolution of 1.4 was obtained, while the use of IPCF-6/D-AlaC4Lac provided a
baseline enantioseparation. Although the combination of SCF-7 and 40 mM D
AlaC4Lac did not affect resolution, it dramatically increased peak efficiency
from 24,000 to 117,000. In the case of warfarin and coumachlor, IPCF-6 and IPCF-7
proved to be the most effective CSs. It is, therefore, concluded that the size of
the cavity and the CF derivatization are the key parameters for the chiral
separation capability. It is also clear from this study that D-AlaC4Lac is
necessary for improved peak efficiencies and resolutions.
PMID- 26444146
TI - Copper-catalyzed arylation of biguanide derivatives via C-N cross-coupling
reactions.
AB - An efficient copper-catalyzed cross-coupling reaction of biguanide hydrochloride
derivatives with both aryl iodides and bromides under mild conditions has been
developed. The reaction occurred in good yields and tolerated aryl halides
containing functionalities such as nitriles, sulfonamides, ethers, and halogens.
Alkyl and cyclic substituted biguanidines were also well tolerated.
PMID- 26444145
TI - Left ventricular outflow tract gradient is associated with reduced capillary
density in hypertrophic cardiomyopathy irrespective of genotype.
AB - BACKGROUND: Coronary microvascular dysfunction (CMD) is an important feature of
hypertrophic cardiomyopathy (HCM), which contributes negatively to symptoms and
long-term outcome. Previous in vivo imaging studies in HCM suggest that left
ventricular outflow tract (LVOT) gradient and genetic status are important
contributors to CMD. CMD may be caused by reduced capillary density. Here, we
investigated whether a reduction in capillary density is related to genetic
status or LVOT gradient severity in an in vitro study of HCM cardiac samples.
METHODS: Using immunofluorescence microscopy, we analysed capillaries (Cap) and
cardiomyocytes (CM) in myectomy specimens from 18 HCM patients with maximum left
ventricular (LV) wall thickness >=15 mm. All subjects exhibited significant LVOT
obstruction, necessitating septal myectomy. In addition, control myocardium from
the LV septal wall was collected at autopsy of 6 individuals that suffered a
noncardiac death. RESULTS: CM area was higher in patients with HCM compared to
controls. Capillary density was significantly lower in patients with HCM compared
with controls (1425 +/- 262 vs. 2543 +/- 509 Cap/mm(2) , P < 0.001), as was the
number of Cap per CM corrected for CM area (2.2 +/- 0.5 vs. 4.2 +/- 0.9 Cap/CM
area, P < 0.001). Capillary density did not differ between genotype-negative and
genotype-positive HCM patients at similar resting LVOT gradients. A significant
correlation was present between resting LVOT gradient and CM area (r = 0.73, P <
0.001), capillary density (r = -0.74, P < 0.001) and the number of Cap per CM
corrected for CM area (r = -0.82, P < 0.001). CONCLUSIONS: Our data indicate that
LVOT gradient, rather than genetic status, is associated with reduced capillary
density in HCM.
PMID- 26444147
TI - Volatilization of elemental mercury from fresh blast furnace sludge mixed with
basic oxygen furnace sludge under different temperatures.
AB - Blast furnace sludge (BFS) is a waste with elevated mercury (Hg) content due to
enrichment during the production process of pig iron. To investigate the
volatilization potential of Hg, fresh samples of BFS mixed with basic oxygen
furnace sludge (BOFS; a residue of gas purification from steel making, processed
simultaneously in the cleaning devices of BFS and hence mixed with BFS) were
studied in sealed column experiments at different temperatures (15, 25, and 35
degrees C) for four weeks (total Hg: 0.178 mg kg(-1)). The systems were regularly
flushed with ambient air (every 24 h for the first 100 h, followed by every 72 h)
for 20 min at a flow rate of 0.25 +/- 0.03 L min(-1) and elemental Hg vapor was
trapped on gold coated sand. Volatilization was 0.276 +/- 0.065 ng (x m: 0.284
ng) at 15 degrees C, 5.55 +/- 2.83 ng (x m: 5.09 ng) at 25 degrees C, and 2.37
+/- 0.514 ng (x m: 2.34 ng) at 35 degrees C. Surprisingly, Hg fluxes were lower
at 35 than 25 degrees C. For all temperature variants, an elevated Hg flux was
observed within the first 100 h followed by a decrease of volatilization
thereafter. However, the background level of ambient air was not achieved at the
end of the experiments indicating that BFS mixed with BOFS still possessed Hg
volatilization potential.
PMID- 26444149
TI - A comparison of single dose dexmedetomidine with propofol for the prevention of
emergence delirium after desflurane anaesthesia in children.
AB - Emergence delirium is a common problem in children recovering from general
anaesthesia. We performed a study comparing emergence characteristics in 100
patients who were randomly allocated to receive either 0.3 MUg.kg(-1)
dexmedetomidine, 1 mg.kg(-1) propofol or saline 0.9% and undergoing infra
umbilical surgery. The Pediatric Anesthesia Emergence Delirium scale was used to
grade emergence delirium. Emergence delirium occurred in 9.4% of children in the
dexmedetomidine group compared with 13.9% in the propofol group and 40.6% in the
control group (p = 0.004). In the dexmedetomidine group, sedation occurred in
62.5% of children at 10 min after transfer to the recovery area, compared with
44.4% in the propofol group and 12.5% in the control group (p = 0.010). We
conclude that dexmedetomidine significantly reduced the incidence of emergence
delirium but this was at the expense of a greater incidence of sedation in the
recovery period.
PMID- 26444150
TI - Lignan enhancement in hairy root cultures of Linum album using coniferaldehyde
and methylenedioxycinnamic acid.
AB - Feeding experiments with hairy root cultures of Linum album have established that
the extracellular coniferaldehyde is a good precursor for production of two
lignans: lariciresinol (LARI) and pinoresinol (PINO). The accumulation of the
LARI, PINO, and podophyllotoxin (PTOX) in hairy roots were enhanced about 14.8-,
8.7-, and 1.5-fold (107.61, 8.7 and 6.42 ug g(-1) Fresh Wight), respectively, by
the addition of coniferaldehyde (2 mM) to the culture media (after 24 hr). This
result was correlated with an increase pinoresinol/lariciresinol reductase (PLR)
expression gene and cinnamyl alcohol dehydrogenase (CAD) activity in the fed
hairy roots. Adding 3,4-(methylendioxy)cinnamic acid (MDCA) precursor did not
influence on the lignans accumulation, but the lignin content of the hairy roots
was increased. Moreover, the expression genes of phenylalanine ammonialyase
(PAL), CAD, and cinnamoyl-CoA reductase (CCR) were influenced after feeding hairy
roots with MDCA.
PMID- 26444151
TI - CRISPR-Based Technologies and the Future of Food Science.
AB - The on-going CRISPR craze is focused on the use of Cas9-based technologies for
genome editing applications in eukaryotes, with high potential for translational
medicine and next-generation gene therapy. Nevertheless, CRISPR-Cas systems
actually provide adaptive immunity in bacteria, and have much promise for various
applications in food bacteria that include high-resolution typing of pathogens,
vaccination of starter cultures against phages, and the genesis of programmable
and specific antibiotics that can selectively modulate bacterial population
composition. Indeed, the molecular machinery from these DNA-encoded, RNA
mediated, DNA-targeting systems can be harnessed in native hosts, or repurposed
in engineered systems for a plethora of applications that can be implemented in
all organisms relevant to the food chain, including agricultural crops trait
enhancement, livestock breeding, and fermentation-based manufacturing, and for
the genesis of next-generation food products with enhanced quality and health
promoting functionalities. CRISPR-based applications are now poised to
revolutionize many fields within food science, from farm to fork. In this review,
we describe CRISPR-Cas systems and highlight their potential for the development
of enhanced foods.
PMID- 26444153
TI - Federal Funding for Food Science--A Tail of Discovery and Careers.
PMID- 26444156
TI - My wish for a global research agenda in nursing.
PMID- 26444157
TI - A study of the Unna Boot compared with the elastic bandage in venous ulcers: a
randomized clinical trial.
AB - OBJECTIVE: to analyze the process of tissue repair in patients with venous ulcers
using inelastic compression therapy (the Unna Boot), in comparison with the use
of the elastic bandage. METHOD: a controlled randomized clinical trial in which
the patients (n=18) were allocated to two groups, those who used the Unna Boot
(group B) and those who used the elastic bandage (group A). The study's follow-up
period was 13 weeks. RESULTS: a significant reduction took place, at the level of
5%, in the area, in square centimeters, of the ulcers of group B (p<0.0001)
throughout the treatment, and there was a tendency of group A for reduction in
the area of the ulcer, in centimeters squared (p=0.06), only after the fifth
week. CONCLUSION: the treatment with the Unna Boot presented better results in
venous ulcers with areas over 10cm2, and the elastic bandage with Petrolatum(r)
gauze in venous ulcers below 10cm2. Brazilian Clinical Trials Register: Trial
(req: 195) and WHO UTN U1111-1122-5489.
PMID- 26444155
TI - Collective dynamics of processive cytoskeletal motors.
AB - Major cellular processes are supported by various biomolecular motors that
usually operate together as teams. We present an overview of the collective
dynamics of processive cytokeletal motor proteins based on recent experimental
and theoretical investigations. Experimental studies show that multiple motors
function with different degrees of cooperativity, ranging from negative to
positive. This effect depends on the mechanical properties of individual motors,
the geometry of their connections, and the surrounding cellular environment.
Theoretical models based on stochastic approaches underline the importance of
intermolecular interactions, the properties of single motors, and couplings with
cellular medium in predicting the collective dynamics. We discuss several
features that specify the cooperativity in motor proteins. Based on this approach
a general picture of collective dynamics of motor proteins is formulated, and the
future directions and challenges are discussed.
PMID- 26444158
TI - Self-care in heart failure patients.
AB - OBJECTIVE: to describe self-care behavior and its associated factors in a sample
of heart failure Brazilian patients. METHOD: descriptive cross-sectional study
with non-probabilistic sample of 116 ambulatory patients undergoing heart failure
treatment. Self-care was evaluated using the Self-Care of Heart Failure Index,
(scores >=70 points=appropriate self-care). Association tests were applied,
considering a descriptive level of 0.05. RESULTS: the mean age of participants
was 57.7 (SD =11.3) years; 54.3% were male; the mean schooling was 5.5 (SD = 4.0)
years; and 74.1% had functional class II-III. The mean scores on the subscales of
the Self-Care of Heart Failure Index indicated inappropriate self-care (self-care
maintenance: 53.2 (SD =14.3), selfcare management: 50.0 (SD = 20.3) and self-care
confidence: 52.6 (SD=22.7)) and it was found low frequencies of participants with
appropriate self-care (self-care maintenance, 6.9%), self-care management (14.7%)
and self-care confidence (19%). Higher scores of the Self-Care of Heart Failure
Index were associated with: reduced left ventricular ejection fraction (p=0.001),
longer time of experience with the disease (p=0.05) and joint monitoring by
physician and nurse (p=0.007). CONCLUSION: investments are needed to improve the
self-care behavior and the nursing can play a relevant role in this improvement.
PMID- 26444159
TI - Relationship between complaints presented by emergency patients and the final
outcome.
AB - OBJECTIVE: to relate complaints presented by emergency room patients, classified
using the Manchester Triage System, with the final outcome
(discharge/death/transfer). METHODS: prospective cohort study, involving 509
patients who were admitted to the emergency room and remained there for more than
24 hours after admission, being monitored to the final outcome. Data were
analyzed with a statistical program using descriptive and analytical statistics.
RESULTS: the mean age of the patients was 59.1 years and 59.3% were male. The
main complaints were unwell adult (130 - 22.5%), shortness of breath in adults
(81 - 14.0%), abdominal pain in adults (58 - 10.0%) and behaving strangely (34 -
5.9%), with 87% of the patients being discharged. More deaths were found in the
patients classified in the severe colors, with 42.8% classified as red, 17.0% as
orange and 8.9% as yellow. Among the patients classified as green, 9.6% died.
CONCLUSION: in the various colors of the Manchester Triage System, death
prevailed in patients that presented the complaints of unwell adult, shortness of
breath, head injury, major trauma, diarrhea and vomiting. The higher the clinical
priority the greater the prevalence of death.
PMID- 26444160
TI - Factors associated with knowledge of the nursing staff at a teaching hospital on
blood transfusion.
AB - OBJECTIVE: to determine whether there is an association between knowledge of the
nursing professionals about blood transfusion and the variables related to the
professional aspects. METHOD: this is an observational, cross-sectional and
quantitative study, carried out at a large general teaching hospital. The sample
consisted of 209 nursing professionals, obtained by simple random sampling. For
data collection, a checklist was used. In the univariate analysis, descriptive
statistics and central trend and dispersion measures were used. In the bivariate
analysis, Student's t-Test, analysis of variance and Pearson's correlation were
used. To determine the predictors, multiple linear regression was applied. The
Institutional Review Board (Opinion number 2434) approved the study. RESULTS: the
overall average knowledge score was 52.66%; in the Pre-transfusion Step, it
corresponded to 53.38%; in the Transfusion Step 51.25% and, in the Post
transfusion Step, 62.68%. The factors related to knowledge were professional
category and received training and/or guidance to accomplish the transfusion
process (p<0.01). CONCLUSION: this study showed the influence of training and
guidance on the knowledge and provided a diagnosis to identify the professionals'
difficulties regarding the transfusion process.
PMID- 26444161
TI - Foot reflexology in feet impairment of people with type 2 diabetes mellitus:
randomized trial.
AB - OBJECTIVE: to evaluate the effect of foot reflexology on feet impairment of
people with type 2 diabetes mellitus. METHOD: this is a randomized, controlled
and blind clinical trial. The sample was comprised by people with type 2 diabetes
mellitus who, after being randomized into Treated group (n = 21) and Control
group (n = 24), received guidelines on foot self-care. To the Treated Group it
was also provided 12 sessions of foot reflexology. The scores of impairment
indicators related to skin and hair, blood circulation, tissue sensitivity and
temperature were measured by means of the instrument for assessing tissue
integrity of the feet of people with diabetes mellitus. Chi-square test, Fisher
exact test, Mann-Whitney test and regression analyzes were applied to the data,
considering a significance level of 5% (P value <0.05). RESULTS: participants who
received the therapy showed better scores in some impairment indicators related
to skin and hair (hair growth, elasticity/turgor, hydration, perspiration,
texture and integrity of the skin/ skin peeling). CONCLUSION: the foot
reflexology had a beneficial effect on feet impairment of people with type 2
diabetes mellitus, which makes it a viable therapy, deserving investment. This
study was registered in the Brazilian Registry of Clinical Trials - RBR-8zk8sz.
PMID- 26444162
TI - Hospitalizations for cardiovascular diseases and the coverage by the family
health strategy.
AB - OBJECTIVE: to verify the correlation between the rates of hospitalization for
primary care-sensitive cardiovascular diseases and the coverage by the Family
Health Strategy of residents of the State of Parana, by regional health
divisions, from 2000 to 2011. METHOD: ecological study developed from data of the
Hospital Information System of the Brazilian Unified Health System (SUS) and the
Department of Primary Care of the Ministry of Health. The rates of
hospitalization for cardiovascular diseases were correlated with the annual
coverage by the Family Health Strategy using Pearson's and Spearman's correlation
coefficients. RESULT: there was a strong and negative correlation in the State of
Parana (r=-0.91; p <0.001) and in most regional health divisions, with the
highest correlations observed in the Metropolitan and Toledo (r =-0.93; p<0.001)
and Paranagua (r=-0.92, p<0.001) regional health divisions. CONCLUSION: the
results suggest that the increase in the coverage by the Family Health Strategy
was an important factor for decrease in the hospitalizations for cardiovascular
conditions among residents of the State of Parana and in most regional health
divisions. Other studies should be performed to analyze the factors and causes in
regional health divisions where there was no correlation with increase in the
Family Health Strategy.
PMID- 26444163
TI - Meaning of leprosy for people who have experienced treatment during the sulfonic
and multidrug therapy periods.
AB - OBJECTIVE: to analyze the meanings of leprosy for people treated during the
sulfonic and multidrug therapy periods. METHOD: qualitative nature study based on
the Vigotski's historical-cultural approach, which guided the production and
analysis of data. It included eight respondents who have had leprosy and were
submitted to sulfonic and multidrug therapy treatments. The participants are also
members of the Movement for Reintegration of People Affected by Leprosy. RESULTS:
the meanings were organized into three meaning cores: spots on the body:
something is out of order; leprosy or hanseniasis? and leprosy from the inclusion
in the Movement for Reintegration of People Affected by Leprosy. CONCLUSION: the
meanings of leprosy for people submitted to both regimens point to a complex
construction thereof, indicating differences and similarities in both treatments.
Health professionals may contribute to the change of the meanings, since these
are socially constructed and the changes are continuous.
PMID- 26444164
TI - Risk behaviors for sexually transmitted diseases among crack users.
AB - OBJECTIVES: to investigate the prevalence and risk behaviors by means of
reporting of sexually transmitted diseases among crack users. METHOD: cross
sectional study carried out with 588 crack users in a referral care unit for the
treatment of chemical dependency. Data were collected by means of face-to-face
interview and analyzed using Stata statistical software, version 8.0. RESULTS: of
the total participants, 154 (26.2%; 95% CI: 22.8-29.9) reported antecedents of
sexually transmitted diseases. Ages between 25 and 30 years (RP: 2.1; 95% CI: 1.0
4.0) and over 30 years (RP: 3.8; 95% CI: 2.1-6.8), alcohol consumption (RP: 1.9;
95% CI: 1.1-3.3), antecedents of prostitution (RP: 1.9; 95% CI: 1.3-2.9) and
sexual intercourse with person living with human immunodeficiency virus/AIDS (RP:
2.7; 95% CI: 1.8-4.2) were independently associated with reporting of sexually
transmitted diseases. CONCLUSION: the results of this study suggest high risk and
vulnerability of crack users for sexually transmitted diseases.
PMID- 26444165
TI - Validation of the content of the prevention protocol for early sepsis caused by
Streptococcus agalactiaein newborns.
AB - OBJECTIVE: to validate the content of the prevention protocol for early sepsis
caused by Streptococcus agalactiaein newborns. METHOD: a transversal, descriptive
and methodological study, with a quantitative approach. The sample was composed
of 15 judges, 8 obstetricians and 7 pediatricians. The validation occurred
through the assessment of the content of the protocol by the judges that received
the instrument for data collection - checklist - which contained 7 items that
represent the requisites to be met by the protocol. The validation of the content
was achieved by applying the Content Validity Index. RESULT: in the judging
process, all the items that represented requirements considered by the protocol
obtained concordance within the established level (Content Validity Index >
0.75). Of 7 items, 6 have obtained full concordance (Content Validity Index 1.0)
and the feasibility item obtained a Content Validity Index of 0.93. The global
assessment of the instruments obtained a Content Validity Index of 0.99.
CONCLUSION: the validation of content that was done was an efficient tool for the
adjustment of the protocol, according to the judgment of experienced
professionals, which demonstrates the importance of conducting a previous
validation of the instruments. It is expected that this study will serve as an
incentive for the adoption of universal tracking by other institutions through
validated protocols.
PMID- 26444166
TI - Instrument to assess the nursing care product: development and content
validation.
AB - OBJECTIVES: develop and validate the content of a tool about nursing care
production. METHOD: the data were collected between 2011 and 2013, based on focus
groups, the application of semistructured questionnaires (prototype test) and the
Delphi technique. The focus groups were used to produce the instrument items and
held at three hospitals in the interior of the State of Sao Paulo, involving 20
nurses. A panel of 10 experts evaluated the instrument. RESULTS: after two phases
of the Delphi technique, the tool consisted of eight items. The content validity
index of the scale corresponded to >=0.9 and the content validity of the items
ranged between 0.8 and 1.0, indicating the maintenance of the structure and
content. The assertion on the applicability in daily nursing practice showed a
content validity index of the scale equal to 0.8. CONCLUSION: this study
permitted the development and content validation of scale on nursing care
production, equipping the nurses in their management practice.
PMID- 26444167
TI - Cultural adaptation to Brazilian Portuguese of the Face, Legs, Activity, Cry,
Consolability revised (FLACCr) scale of pain assessment.
AB - OBJECTIVE: to perform the translation into Brazilian Portuguese and cultural
adaptation of the Face, Legs, Activity, Cry, Consolability revised (FLACCr)
scale, with children under 18 years old, affected by cerebral palsy, presenting
or not cognitive impairment and unable to report their pain. METHOD:
methodological development study of translation into Portuguese and cultural
adaptation of the FLACCr. After approval by the ethics committee, the process
aimed at translation and back-translation, evaluation of translation and back
translation using the Delphi technique and assessment of cultural equivalence.
The process included the five categories of the scale and the four application
instructions, considering levels of agreement equal to or greater than 80%.
RESULTS: it was necessary three rounds of the Delphi technique to achieve
consensus among experts. The agreement achieved for the five categories was: Face
95.5%, Legs 90%, Activity 94.4%, Cry 94.4% and Consolability 99.4%. The four
instructions achieved the following consensus levels: 1st 99.1%, 2nd 99.2%, 3rd
99.1% and 4th 98.3%. CONCLUSION: the method enabled the translation and cultural
adaptation of the FLACCr. This is a study able to expand the knowledge of
Brazilian professionals on pain assessment in children with CP.
PMID- 26444168
TI - Validation of the Comfort scale for relatives of people in critical states of
health.
AB - OBJECTIVE: this methodological study aims to present the construct validity of
the Comfort scale for family members of people in a critical state of health
(ECONF). METHOD: this is a methodological study. The sample was made up of 274
family members of adults receiving inpatient treatment in six Intensive Care
Units (ICU) in the State of Bahia responded to 62 items distributed in 7
dimensions. The validation procedures adopted were based on the techniques of the
Classical Test Theory. RESULTS: the analysis of dimensionality was undertaken
through principal components analysis, a scale being obtained with 55 items
distributed in four factors: Safety, Support, Family member-relative interaction
and Integration with oneself and the everyday. The analysis of the items' ,
discriminative power, undertaken by the item-total correlation-coefficient showed
a good relationship of the items with their respective factors. From the ECONF's
reliability test, from the analysis of internal consistency, a raised Alpha
Cronbach coefficient was obtained for the 4 factors and the general measurement.
CONCLUSION: the comfort scale presented satisfactory psychometric parameters,
thus constituting the first valid instrument for evaluating the comfort of family
members of people in a critical state of health. The advance made by the study
lies in its theoretical framework on comfort, and provides the health team with a
scale based on empirical evidence.
PMID- 26444169
TI - Cross-cultural adaptation and validation of the Protective Nursing Advocacy Scale
for Brazilian nurses.
AB - OBJECTIVE: to adapt culturally and validate the Protective Nursing Advocacy Scale
for Brazilian nurses. METHOD: methodological study carried out with 153 nurses
from two hospitals in the South region of Brazil, one public and the other
philanthropic. The cross-cultural adaptation of the Protective Nursing Advocacy
Scale was performed according to international standards, and its validation was
carried out for use in the Brazilian context, by means of factor analysis and
Cronbach's alpha as measure of internal consistency. RESULTS: by means of
evaluation by a committee of experts and application of pre-test, face validity
and content validity of the instrument were considered satisfactory. From the
factor analysis, five constructs were identified: negative implications of the
advocacy practice, advocacy actions, facilitators of the advocacy practice,
perceptions that favor practice advocacy and barriers to advocacy practice. The
instrument showed satisfactory internal consistency, with Cronbach's alpha values
ranging from 0.70 to 0.87. CONCLUSION: it was concluded that the Protective
Nursing Advocacy Scale - Brazilian version, is a valid and reliable instrument
for use in the evaluation of beliefs and actions of health advocacy, performed by
Brazilian nurses in their professional practice environment.
PMID- 26444170
TI - Risk factor for phlebitis: a questionnaire study of nurses' perception.
AB - OBJECTIVES: to assess nurses' perceptions of risk factors for the development of
phlebitis, with a special focus on the perception of phlebitic potentials of some
infusion medications and solutions. METHOD: a cross-sectional questionnaire
study, which included a sample of 102 nurses. RESULTS: Nurses recognized some
factors that may reduce the incidence of phlebitis; however, more than half of
the nurses were unaware that the material and diameter of the cannula can affect
the incidence rate of phlebitis. Furthermore,underlying disease and high pH of
medications or solutions were identified as potential risk factors, whereas low
pH and low osmolality were not. Nurses identified Vancomycin and Benzylpenicillin
antibiotics with the strongest phlebitic potential. Among other medications and
intravenous fluids, Aminophylline, Amiodaronehydrochloride and Potassium chloride
7.4% were identified as potentially causing phlebitis. CONCLUSION: predisposing
factors for phlebitis relating to patients and administered therapy were
identified by nurses, while some cannula related risk factors, in particular its
physicochemical properties and the time for cannula replacement, were not fully
perceived.
PMID- 26444171
TI - The pain of existing and religion from the perspective of Catholics.
AB - OBJECTIVE: to characterize the understanding of leaders and members of the
Catholic religion on pain of existing. METHOD: 80 Catholics participated in the
study. Data collection was carried out using the Religious Content Assessment
Tool. The content analysis was carried out and arithmetic mean and standard
deviation were calculated. RESULTS: the following categories emerged: length of
affiliation, beginning of the religious practice and affiliation changes,
responsibility for the actions and relationship with death, description of God,
awareness of the existence of profound experiences, possibility of reward,
increased faith in proximity to death, religion as an attempt to explain human
limitations, relationship between religion and science and religion of the past
and present in relation to science. On the instrument, the highest assigning
items were: I believe that nature should be respected (9.96+/-0.19); I believe
that all living beings deserve respect (9.70+/-0.67); make life worth living
(9.70+/-0.78); my life is a transformation process (9.63+/-1.04) and I respect
the diversity of people (9.56+/-0.91). CONCLUSION: it was observed associations
between the participants' perceptions and religious constructs, highlighting the
need to approach the religious phenomenon as part of the human being and
potential resource for management and modulation of the pain of existing.
PMID- 26444172
TI - Readmissions due to traffic accidents at a general hospital.
AB - OBJECTIVE: to verify the occurrence and the causes of hospital readmissions
within a year after discharge from hospitalizations due to traffic accidents.
METHODS: victims of multiple traumas due to traffic accidents were included, who
were admitted to an Intensive Care Unit. Sociodemographic data, accident
circumstances, body regions affected and cause of readmission were collected from
the patient histories. RESULTS: among the 109 victims of traffic accidents, the
majority were young and adult men. Most hospitalizations due to accidents
involved motorcycle drivers (56.9%). The causes of the return to the hospital
were: need to continue the surgical treatment (63.2%), surgical site infection
(26.3%) and fall related to the physical sequelae of the trauma (10.5%). The
rehospitalization rate corresponded to 174/1,000 people/year. CONCLUSION: the
hospital readmission rate in the study population is similar to the rates found
in other studies. Victims of severe limb traumas need multiple surgical
procedures, lengthier hospitalizations and extended rehabilitation.
PMID- 26444173
TI - Evaluation of the quality of the teaching-learning process in undergraduate
courses in Nursing.
AB - OBJECTIVE: to identify aspects of improvement of the quality of the teaching
learning process through the analysis of tools that evaluated the acquisition of
skills by undergraduate students of Nursing. METHOD: prospective longitudinal
study conducted in a population of 60 secondyear Nursing students based on
registration data, from which quality indicators that evaluate the acquisition of
skills were obtained, with descriptive and inferential analysis. RESULTS: nine
items were identified and nine learning activities included in the assessment
tools that did not reach the established quality indicators (p<0.05). There are
statistically significant differences depending on the hospital and clinical
practices unit (p<0.05). CONCLUSION: the analysis of the evaluation tools used in
the article "Nursing Care in Welfare Processes" of the analyzed university
undergraduate course enabled the detection of the areas for improvement in the
teachinglearning process. The challenge of education in nursing is to reach the
best clinical research and educational results, in order to provide improvements
to the quality of education and health care.
PMID- 26444175
TI - Domestic violence against women: representations of health professionals.
AB - OBJECTIVE: to analyze the representations about domestic violence against women,
among health professionals of Family Health Units. METHOD: qualitative study
based on the Theory of Social Representations. Data were collected by means of
evocations and interviews, treating them in the Ensemble de Programmes Pemettant
L'Analyse des Evocations software - EVOC and content analysis. RESULTS: nurses,
physicians, nursing technicians and community health agents participated. The
evocations were answered by 201 professionals and, of these, 64 were interviewed.
The central core of this representation, comprised by the terms "aggression",
"physical-aggression", "cowardice" and "lack of respect", which have negative
connotations and were cited by interviewees. In the contrast zone, comprised by
the terms "abuse", "abuse-power", "pain", "humiliation", "impunity", "suffering",
"sadness" and "violence", two subgroups were identified. The first periphery
contains the terms "fear", evoked most often, followed by "revolt", "low self
esteem" and "submission", and in the second periphery "acceptance" and
"professional support". CONCLUSION: this is a structured representation since it
contains conceptual, imagetic and attitudinal elements. The subgroups were
comprised by professionals working in the rural area and by those who had
completed their professional training course in or after 2004. These presented a
representation of violence different from the representation of the general
group, although all demonstrated a negative connotation of this phenomenon.
PMID- 26444174
TI - Hand hygiene technique quality evaluation in nursing and medicine students of two
academic courses.
AB - OBJECTIVE: because they are health professionals, nursing and medical students'
hands during internships can function as a transmission vehicle for hospital
acquired infections. METHOD: a descriptive study with nursing and medical degree
students on the quality of the hand hygiene technique, which was assessed via a
visual test using a hydroalcoholic solution marked with fluorescence and an
ultraviolet lamp. RESULTS: 546 students were assessed, 73.8% from medicine and
26.2% from nursing. The area of the hand with a proper antiseptic distribution
was the palm (92.9%); areas not properly scrubbed were the thumbs (55.1%). 24.7%
was very good in both hands, 29.8% was good, 25.1% was fair, and 20.3% was poor.
The worst assessed were the male, nursing and first year students. There were no
significant differences in the age groups. CONCLUSIONS: hand hygiene technique is
not applied efficiently. Education plays a key role in setting a good practice
base in hand hygiene, theoretical knowledge, and in skill development, as well as
good practice reinforcement.
PMID- 26444176
TI - An experimental study of an educational intervention to promote maternal self
efficacy in breastfeeding.
AB - OBJECTIVE: to build, validate and assess an educational intervention using the
flip chart titled "I Can Breastfeed My Child." METHOD: an experimental study
using a pretest, intervention and posttest, as well as a control group. A total
of 201 women, who had been hospitalized immediately, for at least 6 hours,
postpartum. The mothers were allocated to the intervention (100 women) or control
groups (101 women) according to the length of their hospital stay. The
effectiveness of the flip chart was assessed by applying the Breastfeeding Self
Efficacy Scale - Short-Form at admission, discharge and by telephone in the
second month postpartum. The intervention and control groups were similar in
their socio-demographic, obstetric and gynecological variables. RESULTS: the
intervention was beneficial because mothers in the intervention group had higher
self-efficacy scores, more mothers continued breastfeeding and mothers had a
longer duration of exclusive breastfeeding, both at the time of hospital
discharge and at the second month postpartum, with statistically significant
associations. CONCLUSIONS: this experimental study assessed the educational
strategy mediated via the flip chart titled "I Can Breastfeed My Child" as being
effective both in increasing self-efficacy and increasing the duration of
breastfeeding.
PMID- 26444177
TI - Association between depression and work stress in nursing professionals with
technical education level.
AB - OBJECTIVE: to analize the relationship between depression and work stress in
nursing professionals with technical education level of a teaching hospital in a
city of the state of Sao Paulo. METHODS: a cross-sectional study was carried out
with 310 nursing technicians and nursing assistants, randomly selected. The
outcome analyzed was the report of depression and its relationship with high
levels of work stress, measured using the Job Stress Scale. Descriptive
statistics and logistic regression were performed. RESULTS: the prevalence of
depression in this study was 20%, and it was more expressive in females, aged
over 40 years, living without a partner and in smokers. The chance of depression
was twice as high among professionals showing high levels of work stress, even
after multiple regression adjusting. CONCLUSION: depressive symptoms were
strongly associated with high stress levels among nursing assistants and nursing
technicians, evidencing a problem to be considered along with the planning of
specific intervention programs for this population, as well as the need for
better cases management by the supervisors.
PMID- 26444178
TI - Efficacy and effectiveness of alcohol in the disinfection of semi-critical
materials: a systematic review.
AB - OBJECTIVE: to assess the efficacy and the effectiveness of 60-80% alcohol (v/v)
in the disinfection of semi-critical materials which were either previously
cleaned or not. METHOD: studies obtained from BIREME, IBECS, MEDLINE, ScIELO,
PubMed, Ask Medline web portals, and references from other studies. Criteria were
created to assess the methodological quality of articles. Out of the 906 studies
found, 14 have been included. RESULTS: after materials were disinfected with
alcohol, microorganisms were detected in 104/282 (36.9%) effectiveness tests and
in 23/92 (25.0%) efficacy tests that were conducted. In the field studies,
disinfection was not achieved for 74/218 (33.9%) of the products that were
submitted to previous cleaning and for 30/64 (46.9%) of the ones which were not
submitted to previous cleaning. In the experimental studies, alcohol disinfection
was not efficacy in 11/30 (36.7%) and 12/62 (19.4%) of products, respectively.
The studies were not found to have followed standardized methods. CONCLUSION:
disinfection of semi-critical products with alcohol 70% - or in an approximate
concentration - cannot be recommended to all health care products in an
unrestricted way. However, according to the type of semi-critical product,
disinfection can be attained with or without previous cleaning.
PMID- 26444179
TI - An integrative literature review on nursing interventions aimed at increasing
self-care among heart failure patients.
AB - OBJECTIVE: to analyze and summarize knowledge concerning critical components of
interventions that have been proposed and implemented by nurses with the aim of
optimizing self-care by heart failure patients. METHODS: PubMed and CINAHL were
the electronic databases used to search full peer-reviewed papers, presenting
descriptions of nursing interventions directed to patients or to patients and
their families and designed to optimize self-care. Forty-two studies were
included in the final sample (n=4,799 patients). RESULTS: this review pointed to
a variety and complexity of nursing interventions. As self-care encompasses
several behaviors, interventions targeted an average of 3.6 behaviors.
Educational/counselling activities were combined or not with cognitive behavioral
strategies, but only about half of the studies used a theoretical background to
guide interventions. Clinical assessment and management were frequently
associated with self-care interventions, which varied in number of sessions (1 to
30); length of follow-up (2 weeks to 12 months) and endpoints. CONCLUSIONS: these
findings may be useful to inform nurses about further research in self-care
interventions in order to propose the comparison of different modalities of
intervention, the use of theoretical background and the establishment of
endpoints to evaluate their effectiveness.
PMID- 26444180
TI - Burden and quality of life of mothers of children and adolescents with chronic
illnesses: an integrative review.
AB - OBJECTIVE: to identify and analyze the evidence available regarding evaluation of
burden and quality of life of mothers who are caregivers for children and
adolescents with chronic illnesses. METHOD: an integrative review, undertaken in
the electronic sources MEDLINE; Academic Search Premier; CINAHL; LILACS; SciELO
and PubMed, between 2010 and 2014. RESULTS: among the 22 documents selected,
there was a predominance of convenience samples and non-experimental transversal
designs, at the levels IV and III2. The caregiver burden scales used were the
Zarit Burden Interview and Montgomery-Borgatta Caregiver Burden Scale-Revised
along with the following instruments for evaluating quality of life: The World
Health Organization Quality of Life-BREF Scale; Self-report questionnaires; The
Ulm Quality of Life Inventory for Parents of chronically ill children; Asthma
Caregiver Quality of Life Questionnaire; and the Nottingham Health Profile.
Quality-of-life appears to be influenced in a complex and interrelated way by the
physical and mental health of the mothers who are caregivers, in accordance with
their level of independence, social relationships, environment, and the extent to
which they see themselves as burdened. CONCLUSION: the revealing of the results
for the evaluation of burden and quality of life of mothers who are caregivers
has implications for the planning and implementation of effective interventions,
by the multidisciplinary team, if they are to relieve the burden.
PMID- 26444181
TI - Major Effect of the Syndrome of Rapid-Onset End-Stage Renal Disease on the Use of
Arteriovenous Fistulas: High Rates of Initiation of Hemodialysis With
Hemodialysis Catheter in the United States.
PMID- 26444182
TI - Two equivalent methyl internal rotations in 2,5-dimethylthiophene investigated by
microwave spectroscopy.
AB - The microwave spectrum of 2,5-dimethylthiophene, a sulfur-containing five
membered ring with two conjugated double bonds, was recorded in the frequency
range from 2 to 40 GHz using molecular beam Fourier transform technique. Highly
accurate molecular parameters were determined. A labeling scheme for the group
G36 written as the semi-direct product (C(I)(3) * C(I)(3)) ? C(2v) was
introduced.
PMID- 26444184
TI - Controlling Electrical Conductance through a pi-Conjugated Cruciform Molecule by
Selective Anchoring to Gold Electrodes.
AB - Tuning charge transport at the single-molecule level plays a crucial role in the
construction of molecular electronic devices. Introduced herein is a promising
and operationally simple approach to tune two distinct charge-transport pathways
through a cruciform molecule. Upon in situ cleavage of triisopropylsilyl groups,
complete conversion from one junction type to another is achieved with a
conductance increase by more than one order of magnitude, and it is consistent
with predictions from ab initio transport calculations. Although molecules are
well known to conduct through different orbitals (either HOMO or LUMO), the
present study represents the first experimental realization of switching between
HOMO- and LUMO-dominated transport within the same molecule.
PMID- 26444183
TI - Hormonal contraceptive use before hCG remission does not increase the risk of
gestational trophoblastic neoplasia following complete hydatidiform mole: a
historical database review.
AB - OBJECTIVE: To re-evaluate the safety of hormonal contraceptives (HC) after
uterine evacuation of complete hydatidiform mole (CHM). DESIGN: Historical
database review. SETTING: Charing Cross Hospital Gestational Trophoblastic
Disease Centre, London, United Kingdom. POPULATION: Two thousand four hundred and
twenty-three women with CHM of whom 154 commenced HC while their human chorionic
gonadotropin (hCG) was still elevated, followed between 2003 and 2012. METHODS:
We compared time to hCG remission between HC users and nonusers. The relationship
between HC use and gestational trophoblastic neoplasia (GTN) development was
assessed. The relationship between HC use and a high International Federation of
Gynecology and Obstetrics (FIGO) risk score was determined. MAIN OUTCOME
MEASURES: Time to hCG remission, risk of developing postmolar GTN and proportion
of women with high FIGO risk score. RESULTS: No relationship was observed between
HC use with mean time to hCG remission (HC users versus non-users: 12 weeks in
both, P = 0.19), GTN development (HC users versus non-users: 20.1 and 16.7%, P =
0.26) or high-risk FIGO score (HC users versus nonusers: 0% and 8%, P = 0.15).
Moreover, no association between HC and GTN development was found, even when an
age-adjusted model was used (OR = 1.37, 95% CI 0.91-2.08, P = 0.13). CONCLUSIONS:
The use of current HC is not associated with development of postmolar GTN or
delayed time to hCG remission. Therefore, HC can be safely used to prevent a new
conception following CHM regardless of hCG level. TWEETABLE ABSTRACT: Non
concurrent cohort study to re-evaluate the safety of low dose HCs after uterine
evacuation of CHM.
PMID- 26444186
TI - Targeted Droplet-Digital PCR as a Tool for Novel Deletion Discovery at the DFNB1
Locus.
AB - Pathogenic variants at the DFNB1 locus encompassing the GJB2 and GJB6 genes
account for 50% of autosomal-recessive, congenital nonsyndromic hearing loss in
the United States. Most cases are caused by sequence variants within the GJB2
gene, but a significant number of DFNB1 patients carry a large deletion (GJB6
D13S1830) in trans with a GJB2 variant. This deletion lies upstream of GJB2 and
was shown to reduce GJB2 expression by disrupting unidentified regulatory
elements. First-tier genetic testing for hearing loss includes GJB2 sequence and
GJB6-D13S1830 deletion analysis; however, several other deletions in this locus,
each with distinct breakpoints, have been reported in DFNB1 patients and are
missed by current panels. Here, we report the development of a targeted droplet
digital polymerase chain reaction-based assay for comprehensive copy-number
analysis at the DFNB1 locus that detects all deletions reported to date. This
assay increased detection rates in a multiethnic cohort of 87 hearing loss
patients with only one identified pathogenic GJB2 variant. We identify two
deletions, one of which is novel, in two patients (2/87 or 2.3%), suggesting that
other pathogenic deletions at the DFNB1 locus may be missed. Mapping the assayed
DFNB1 deletions also revealed a ~ 95 kb critical region, which may harbor the
GJB2 regulatory element(s).
PMID- 26444185
TI - Polydrug Use and HIV Risk Among People Who Inject Heroin in Tijuana, Mexico: A
Latent Class Analysis.
AB - BACKGROUND: Although most people who inject drugs (PWID) in Tijuana, Mexico,
primarily inject heroin, injection and non-injection use of methamphetamine and
cocaine is common. We examined patterns of polydrug use among heroin injectors to
inform prevention and treatment of drug use and its health and social
consequences. METHODS: Participants were PWID residing in Tijuana, aged >=18
years who reported heroin injection in the past six months and were recruited
through respondent-driven sampling (n = 1,025). Latent class analysis was
conducted to assign individuals to classes on a probabilistic basis, using four
indicators of past six-month polydrug and polyroute use: cocaine injecting,
cocaine smoking or snorting, methamphetamine injecting, and methamphetamine
smoking or snorting. Latent class membership was regressed onto covariates in a
multinomial logistic regression. RESULTS: Latent class analyses testing 1, 2, 3,
and 4 classes were fit, with the 3-class solution fitting best. Class 1 was
defined by predominantly heroin use (50.2%, n = 515); class 2 by methamphetamine
and heroin use (43.7%, n = 448), and class 3 by methamphetamine, cocaine, and
heroin use (6.0%, n = 62). Bivariate and multivariate analyses indicated a group
of methamphetamine and cocaine users that exhibited higher-risk sexual practices
and lower heroin injecting frequency, and a group of methamphetamine users who
were younger and more likely to be female. CONCLUSIONS: Discrete subtypes of
heroin PWID were identified based on methamphetamine and cocaine use patterns.
These findings have identified subtypes of heroin injectors who require more
tailored interventions to reduce the health and social harms of injecting drug
use.
PMID- 26444187
TI - Modification of solid lipid nanoparticles loaded with nebivolol hydrochloride for
improvement of oral bioavailability in treatment of hypertension: polyethylene
glycol versus chitosan oligosaccharide lactate.
AB - Nebivolol (NB)-loaded solid lipid nanoparticles (SLNs) were prepared and modified
with chitosan oligosaccharide lactate (COL) and polyethylene glycol (PEG)
stearate for improvement of its oral bioavailability. Compritol, poloxamer and
lecithin were used for the preparation of SLNs by homogenisation method. After in
vitro characterisation effect of lipase, pepsin, or pancreatin on degradation and
release rate were investigated. Cytotoxicity and permeation were studied on Caco
2 cells. As COL concentration increased in SLNs, size and zeta potential
increased. PEG concentration was reversely proportional to particle size with no
change in zeta potential. Encapsulation efficiencies (EEs) were determined as 84
98%. DSC confirmed solubilisation of NB in lipid matrix. A sustained release with
no burst effect was determined. The presence of enzymes affected the release.
SLNs did not reveal cytotoxicity and highest permeability was obtained with PEG
modification. PEG-modified SLNs could be offered as a promising strategy for oral
delivery of NB.
PMID- 26444188
TI - Electromagnetic fields: activities in the European Commission with a focus on
research projects and the Scientific Committee of Emerging and Newly Identified
Health Risks (SCENIHR).
AB - The article summarizes the main activities of the European Commission concerning
electromagnetic fields. It explains also the regulatory context, with a special
focus on past and current research projects funded by the European Union and the
role of the SCENIHR in assessing risks related to EMF. Main conclusions of the
SCENIHR opinion adopted in 2015 on EMF are reported.
PMID- 26444189
TI - A need to provide explanations for observed biological effects of radiofrequency
exposure.
AB - Although there is scientific consensus that radiofrequency (RF) exposure at high
intensity can cause thermal effects, including well-established adverse health
effects, there is still considerable controversy on whether low-intensity RF
exposure can cause biological effects, especially adverse health effects. The
objective of this paper is to describe several reported "non-thermal" effects
that were later shown to be due to a weak thermal effect or an experimental
artifact by properly conducted and thorough follow-on scientific research. First,
the multiple factors that can cause different RF energy absorption in biological
tissues are reviewed and second, several examples of experimental artifacts in
published papers are described to demonstrate the importance of paying attention
to dosimetry and temperature control. For example, isolated nerve response
studies show that when temperature of the RF-exposed tissues is controlled,
effects disappeared. During RF exposure, conductive electrodes routinely used in
physiological studies have been shown to cause field intensification at the tips
or contacts of the electrodes with biological tissue; thus, the RF exposure at
the site of measurement could be much higher than the incident field. In some in
vitro studies, a lack of temperature uniformity in RF-exposed cell cultures and
rate of heating explain changes originally reported to be due to low-level RF
exposure. In other studies, detailed dosimetry studies have identified artifacts
that explain the reasons why so-called "non-thermal" effects were mistakenly
reported. Researchers should look for explanations for their own findings, and
not expect others to figure out what was the reason for their observed effects.
PMID- 26444190
TI - Near-field radiofrequency electromagnetic exposure assessment.
AB - Personal wireless telecommunication devices, such as radiofrequency (RF)
electromagnetic field (EMF) sources operated in vicinity of human body, have
possible adverse health effects. Therefore, the correct EMF assessment is
necessary in their near field. According to international near-field measurement
criteria, the specific absorption rate (SAR) is used for absorbed energy
distribution assessment in tissue simulating liquid phantoms. The aim of this
investigation is to validate the relationship between the H-field of incident EMF
and absorbed energy in phantoms. Three typical wireless telecommunication system
frequencies are considered (900, 1800 and 2450 MHz). The EMF source at each
frequency is an appropriate half-wave dipole antenna and the absorbing medium is
a flat phantom filled with the suitable tissue simulating liquid. Two methods for
SAR estimation have been used: standard procedure based on E-field measured in
tissue simulating medium and a proposed evaluation by measuring the incident H
field. Compared SAR estimations were performed for various distances between
sources and phantom. Also, these research data were compared with simulation
results, obtained by using finite-difference time-domain method. The acquired
data help to determine the source near-field space characterized by the smallest
deviation between SAR estimation methods. So, this region near the RF source is
suitable for correct RF energy absorption assessment using the magnetic component
of the RF fields.
PMID- 26444191
TI - An historical overview of the activities in the field of exposure and risk
assessment of non-ionizing radiation in Bulgaria.
AB - The exposure and risk evaluation process in Bulgaria concerning non-ionizing
radiation health and safety started in the early 1970s. Then, the first research
laboratory "Electromagnetic fields in the working environment" was founded in the
framework of the Centre of Hygiene, belonging to the Medical Academy, Sofia. The
main activities were connected with developing legislation, new equipment for
measurement of electromagnetic fields, new methods for measurement and exposure
assessment, in vivo and human studies for developing methods, studying the effect
of non-ionizing radiation on human body, developing exposure limits. Most of the
occupations as metal industry, plastic welding, energetics, physiotherapy,
broadcasting, telephone stations, computer industry, etc., have been covered by
epidemiological investigations and risk evaluation. In 1986, the ANSI standard
for safe use of lasers has been implemented as national legislation that gave the
start for studies in the field of risk assessment concerning the use of lasers in
industry and medicine. The environmental exposure studies started in 1991
following the very fast implementation of the telecommunication technologies.
Now, funds for research are very insignificant, and studies in the field of risk
assessment are very few. Nevertheless, Bulgaria has been an active member of the
WHO International EMF Project, since 1997, and that gives good opportunity for
collaboration with other Member states, and for implementation of new approach in
the EMF policy for workers and people's protection against non-ionizing radiation
exposure.
PMID- 26444192
TI - XXIst century magnetotherapy.
AB - This paper discusses the state of the art therapeutic application of magnetic and
electromagnetic fields (EMF) in treatment of various medical problems - from pain
relief to musculoskeletal trauma, to vascular and endocrine disorders. The paper
describes problems related to physical parameters of used fields, biophysical
dosimetry, clinical protocols, and safety of the device operators. Clinical
benefits and mechanisms of action are also discussed.
PMID- 26444193
TI - The role of cell hydration in realization of biological effects of non-ionizing
radiation (NIR).
AB - The weak knowledge on the nature of cellular and molecular mechanisms of
biological effects of NIR such as static magnetic field, infrasound frequency of
mechanical vibration, extremely low frequency of electromagnetic fields and
microwave serves as a main barrier for adequate dosimetry from the point of
Public Health. The difficulty lies in the fact that the biological effects of NIR
depend not only on their thermodynamic characteristics but also on their
frequency and intensity "windows", chemical and physical composition of the
surrounding medium, as well as on the initial metabolic state of the organism.
Therefore, only biomarker can be used for adequate estimation of biological
effect of NIR on organisms. Because of the absence of such biomarker(s),
organizations having the mission to monitor hazardous effects of NIR
traditionally base their instruction on thermodynamic characteristics of NIR.
Based on the high sensitivity to NIR of both aqua medium structure and cell
hydration, it is suggested that cell bathing medium is one of the primary targets
and cell hydration is a biomarker for NIR effects on cells and organisms. The
purpose of this article is to present a short review of literature and our own
experimental data on the effects of NIR on plants' seeds germination, microbe
growth and development, snail neurons and heart muscle, rat's brain and heart
tissues.
PMID- 26444194
TI - Change of growth pattern, metabolism, and quality and quantity of maize plants
after irrigation with magnetically treated water.
AB - Water molecules can be affected by magnetic fields (MF) due to their bipolar
characteristics. In the present study maize plants, from sowing to the end period
of generative stage, were irrigated with magnetically treated water (MTW).Tap
water was treated with MF by passing through a locally designed alternative
magnetic field generating apparatus (110 mT). Irrigation with MTW increased the
ear length and fresh weight, 100-grain fresh and dry weights, and water
productivity (119.5%, 119.1%, 114.2%, 116.6% and 122.3%, respectively), compared
with the control groups. Levels of photosynthetic pigments i.e. chlorophyll a and
b, and the contents of anthocyanin and flavonoids of the leaves were increased
compared to those of non-treated ones. Increase of the activity of superoxide
dismutase (SOD) and ascorbate peroxidase (APX) in leaves of the treated plants
efficiently scavenged active oxygen species and resulted in the maintenance of
photosynthetic membranes and reduction of malondealdehyde. Total ferritin, sugar,
iron and calcium contents of kernels of MTW-irrigated plants were respectively
122.9%, 167.4%, 235% and 185% of the control ones. From the results presented
here it can be concluded that the influence of MF on living plant cells, at least
in part, is mediated by water. The results also suggest that irrigation of maize
plant with MTW can be applied as a useful method for improvement of quantity and
quality of it.
PMID- 26444195
TI - Investigation on the effect of static magnetic field up to 30 mT on viability
percent, proliferation rate and IC50 of HeLa and fibroblast cells.
AB - We have investigated the effects of static magnetic field (SMF) on the viability
of the human cervical cancer (HeLa) cell line and fibroblast cells. The cells
were cultured in DMEM medium and treated several times (24, 48,72 and 96 h) and
at several intensities (5, 10, 20 and 30 mT) of magnetic field (MF). The
cytotoxicity and cell viability percent in treated cells were performed using MTT
assay by evaluating mitochondrial dehydrogenase activity. The MF ability on
inducing cell death or inhibiting biochemical function was reported as cell death
percent. The results showed that the increase of MF intensity and the time that
cells were exposed to this treatment increased sharply cell death percent and
proliferation rate in HeLa cell compare to fibroblast cells. Our data suggest
that SMF biological effects on cell death were different in our selected targets.
Cell type and time of exposure have been therefore found to be significant
factors. These findings could be used to improve new effective method using SMF
in conjunction with the common therapeutic approaches.
PMID- 26444196
TI - Occupational exposure of personnel operating military radio equipment:
measurements and simulation.
AB - Technical literature provides numerous studies concerning radiofrequency exposure
measurements for various radio communication devices, but there are few studies
related to exposure of personnel operating military radio equipment. In order to
evaluate exposure and identify cases when safety requirements are not entirely
met, both measurements and simulations are needed for accurate results. Moreover,
given the technical characteristics of the radio devices used in the military,
personnel mainly operate in the near-field region so both measurements and
simulation becomes more complex. Measurements were made in situ using a broadband
personal exposimeter equipped with two isotropic probes for both electric and
magnetic components of the field. The experiment was designed for three different
operating frequencies of the same radio equipment, while simulations were made in
FEKO software using hybrid numerical methods to solve complex electromagnetic
field problems. The paper aims to discuss the comparative results of the
measurements and simulation, as well as comparing them to reference levels
specified in military or civilian radiofrequency exposure standards.
PMID- 26444197
TI - Thermo-induced modifications and selective accumulation of glucose-conjugated
magnetic nanoparticles in vivo in rats - increasing the effectiveness of magnetic
assisted therapy - pilot study.
AB - Ferro-Magnetic nanoparticles (Fe-MNP) have gained a lot of attention in
biomedical and industrial applications due to their biocompatibility, ease of
surface modification and paramagnetic properties. The basic idea of our study is
whether it is possible to use glucose-conjugate Fe-MNP (Glc-Fe-MNP) for targeting
and more accurate focusing in order to increase the effect of high-frequency
electromagnetic fields induced hyperthermia in solid tumors. Tumors demonstrate
high metabolic activity for glucose in comparison with other somatic
cells.Increasing of accumulation of glucose conjugated (Glc)-Fe-MNP on tumor site
and precision of radio frequency electro-magnetic field (RF-EMF) energy
absorption in solid tumors, precede RF-EMF induced hyperthermia. Rat model for
monitoring the early development of breast cancer. Twenty female Wistar rats (MU
line-6171) were divided into two groups of 10 rats that were either treated with
N-methyl-N-nitrosourea to induce breast cancer and 10 with carrageenan to induce
inflammation (control). Glc-Fe-MNP can offer a solution to increase hyperthermia
effect to the desired areas in the body by accumulation and increasing local
concentration due to high tissue metabolic assimilation. In this condition, it is
considered that the magnetization of the nanoparticles is a single-giant magnetic
moment, the sum of all the individual magnetic moments and is proportional to the
concentration of Glc-Fe-MNP.
PMID- 26444198
TI - The treatment of tendon injury with electromagnetic fields evidenced by advanced
ultrasound image processing.
AB - This article presents a novel modality for accelerating the repair of tendon and
ligament lesions by means of a specifically designed electromagnetic field in an
equine model. This novel therapeutic approach employs a delivery system that
induces a specific electrical signal from an external magnetic field derived from
Superconductive QUantum Interference Device (SQUID) measurements of injured vs.
healthy tissue. Evaluation of this therapy technique is enabled by a proposed new
technology described as Predictive Analytical Imagery (PAITM). This technique
examines an ultrasound grayscale image and seeks to evaluate it by means of look
ahead predictive algorithms and digital signal processing. The net result is a
significant reduction in background noise and the production of a high-resolution
grayscale or digital image.
PMID- 26444199
TI - Body mass index as a risk prediction and prevention factor for professional mixed
low-intensity EMF burden.
AB - The exposure conditions in the physiotherapy are characterized with various
sources emitting electromagnetic fields (EMF) in different frequency ranges. Very
little is known about the exposure modalities' influence on the operators. In
this article, we present the effects of EMF on personnel morbidity profile
dependent on the body mass index (BMI) increase. By cross-tabulation, the role of
higher BMI on enhancing the EMF vulnerability potential is confirmed. The
correlation of the higher BMI with some serious diseases and conditions'
development has been evidenced statistically significant. Vy the whole-studied
group, a general tendency for allergy, cardiovascular diseases, sleep disruption
and age-shortened menopause, as well as allergy and leiomyoma in the expositional
criteria subgroups (ESG), formed for the purposes of this study, is evidenced.
The three ESGs are formed on work residence duration in the electrolight therapy
section. The first - up to four working hour daily, the second - the entire
working day (7 h) and the third group is not residenced in the electrolight
therapy section. We hypothesize two signaling ways of interaction of the
chronically low-intensity EMF and the higher BMI as the most likely: hormonal -
by melatonin levels decrease due to estrogen levels increasing and endocrine -
mast-cells auto replication and degranulation stimulation. Based on the results
of the study, the BMI increase as an observed control factor in the prediction of
the professional risk can be recommended.
PMID- 26444200
TI - Extremely low frequency (ELF) stray magnetic fields of laboratory equipment: a
possible co-exposure conducting experiments on cell cultures.
AB - Measurements of extremely low frequency (ELF) magnetic fields were conducted in
the environment of commercial laboratory equipment in order to evaluate the
possible co-exposure during the experimental processes on cell cultures. Three
types of device were evaluated: a cell culture CO2 incubator, a thermostatic
water bath and a laboratory shaker table. These devices usually have electric
motors, heating wires and electronic control systems, therefore may expose the
cell cultures to undesirable ELF stray magnetic fields. Spatial distributions of
magnetic field time domain signal waveform and frequency spectral analysis (FFT)
were processed. Long- and short-term variation of stray magnetic field was also
evaluated under normal use of investigated laboratory devices. The results show
that the equipment under test may add a considerable ELF magnetic field to the
ambient environmental magnetic field or to the intentional exposure to ELF, RF or
other physical/chemical agents. The maximum stray magnetic fields were higher
than 3 uT, 20 uT and 75 uT in the CO2 incubator, in water bath and on the
laboratory shaker table, respectively, with high variation of spatial
distribution and time domain. Our investigation emphasizes possible confounding
factors conducting cell culture studies related to low-level ELF-EMF exposure due
to the existing stray magnetic fields in the ambient environment of laboratory
equipment.
PMID- 26444201
TI - Protect children from EMF.
AB - The twenty-first century is marked with aggressive development of the wireless
communications (satellite, mobile phones, Internet, Wi-Fi). In addition to
thousand of satellites that deliver radio and TV signals, large satellite and
base station networks secure intensive instant delivery of audio and video
information. It is fair to say that that the entire civilization, both biosphere
and mankind are exposed to continuous exposure of multitude of radiofrequency
(RF) signals. It should be taken into account that the entire world population is
exposed to exponentially increasing RF radiation from base stations and satellite
antennas. While several years ago the potential hazard was connected with
placement of mobile phones close to human head, today "smart phones" represent
small, but powerful computers continuously receiving audio and video data. The
largest group of users is the children and teenagers who "need" to communicate
nearly 24 h a day. This is even more important because cell phones and tablets
may be seen in the hands of children as little as two years in age. There is no
way to assess and predict the potential damages of children brain, vision and
hearing under exposure to RF radiation. The WHO precautionary principle and IARC
classification must be applied in discussing the potential hazard of the use of
today's and tomorrow's communication devices.
PMID- 26444202
TI - Electromagnetic fields from mobile phone base station - variability analysis.
AB - The article describes the character of electromagnetic field (EMF) in mobile
phone base station (BS) surroundings and its variability in time with an emphasis
on the measurement difficulties related to its pulse and multi-frequency nature.
Work also presents long-term monitoring measurements performed recently in
different locations in Poland - small city with dispersed building development
and in major polish city - dense urban area. Authors tried to determine the
trends in changing of EMF spectrum analyzing daily changes of measured EMF levels
in those locations. Research was performed using selective electromagnetic meters
and also EMF meter with spectrum analysis.
PMID- 26444203
TI - Subjective symptoms and their evolution in a small group of magnetic resonance
imaging (MRI) operators recently engaged.
AB - Using a specific questionnaire, we examined subjective symptoms in a group of 17
physicians (9 males and 8 females, mean age 32.9 +/- 3.71), attending a
Postgraduate Medical School in Radiology and engaged in MRI for less than 1 year.
Sixteen subjects (94%) reported the presence of at least one of the investigated
symptoms during the period of MRI activity. The main symptoms were: unusual
drowsiness/tiredness (88%), concentration problems (82%), headaches (76%), sleep
disorders (47%), nausea (47%), illusion of movement (47%) and dizziness/vertigo
(35%); the former two were subjectively related to MRI by the majority of the
operators. These symptoms appeared (or worsened) in more than 15 min and, in the
vast majority disappeared 30 min, or more, after the end of exposure. In 13
subjects (81%), the symptom (or some symptoms) appeared at least weekly. In this
small group of health care workers recently exposed to MRI, the prevalence of
subjective symptoms was higher than reported in other similar studies but,
notably, the majority of subjects (77%) reported a regression within 4-8 weeks,
suggesting some form of adaptation.
PMID- 26444204
TI - Radiofrequency electromagnetic radiation exposure inside the metro tube
infrastructure in Warszawa.
AB - Antennas from various wireless communications systems [e.g. mobile phones base
transceiver stations (BTS) and handsets used by passengers, public Internet
access, staff radiophone transmitters used between engine-drivers and traffic
operators] emitting radiofrequency electromagnetic radiation (RF-EMR) are used
inside underground metro public transportation. Frequency-selective exposimetric
investigations of RF-EMR exposure inside the metro infrastructure in Warsaw
(inside metro cars passing between stations and on platforms) were performed. The
statistical parameters of exposure to the E-field were analyzed for each
frequency range and for a total value (representing the wide-band result of
measurements of complex exposure). The recorded exposimetric profiles showed the
dominant RF-EMR sources: handsets and BTS of mobile communication systems (GSM
900 and UMTS 2100) and local wireless Internet access (WiFi 2G). Investigations
showed that the GSM 900 system is the dominant source of exposure - BTS
(incessantly active) on platforms, and handsets - used by passengers present
nearby during the tube drive. The recorded E-field varies between sources (for
BTS were: medians - 0.22 V/m and 75th percentile - 0.37 V/m; and for handsets:
medians - 0.28 V/m and 75th percentile - 0.47 V/m). Maximum levels (peaks) of
exposure recorded from mobile handsets exceeded 10 V/m (upper limit of used
exposimeters). Broadband measurements of E-field, including the dominant signal
emitted by staff radiophones (151 MHz), showed that the level of this exposure of
engine-drivers does not exceed 2.5 V/m.
PMID- 26444205
TI - Dynamics of the public concern and risk communication program implementation.
AB - The public concern about electromagnetic field (EMF) exposure varies due to
different reasons. A part of them are connected with the better and higher
quality of information that people receive from science, media, Internet, social
networks, industry, but others are based on good communication programs performed
by the responsible institutions, administration and persons. Especially, in
Bulgaria, public concern follows interesting changes, some of them in correlation
with the European processes of concern, but others following the economic and
political processes in the country. Here, we analyze the dynamics of the public
concern over the last 10 years. Our explanation of the decrease of the people's
complaints against EMF exposure from base stations for mobile communication is as
a result of our risk communication program that is in implementation for >10
years.
PMID- 26444206
TI - Risk Factors for Stillbirth: Findings from a Population-Based Case-Control Study,
Haryana, India.
AB - BACKGROUND: Stillbirth is a prevalent adverse outcome of pregnancy in India
despite efforts to improve care of women during pregnancy. Risk factors for
stillbirths include sociodemographic factors, medical complications during
pregnancy, intake of harmful drugs, and complications during delivery. The
objective of the study was to examine the risk factors for stillbirth with a
focus on sex selection drugs (SSDs). METHODS: A population-based case-control
study was undertaken in Haryana. Cases of stillbirths were identified from the
Maternal Infant Death Review System portal of Haryana state for the months of
August-September 2014. A consecutive birth from the same geographical area as the
case was selected as the control. The sample size was 325 per group. Mothers were
interviewed using a validated tool. Bivariate analyses and logistic regression
were conducted to examine the association between risk factors and stillbirth.
Attributable risk proportions (ARP) and population attributable risk proportions
(PARP) were estimated. RESULTS: The sociodemographic profiles of the cases and
controls were similar. History of intake of SSDs [adjusted odds ratio (OR) 2.6,
95% confidence interval (CI) 1.5, 4.5] emerged as a risk factor. Other
significant factors were preterm <37 weeks (OR 3.5, 95% CI 2.1, 6.0), history of
previous stillbirths (OR 4.0, 95% CI 2.1, 7.8), and complications during labour
(OR 3.3, 95% CI 2.1, 5.3). Estimates of the ARP and PARP for intake of SSDs were
0.60 (95% CI 0.32, 0.77) and 0.1 (95% CI -0.13, 0.28), respectively. CONCLUSIONS:
SSDs could be attributed as a risk factor in a fifth of the cases of stillbirths.
The number needed to harm for the use of SSDs in causing adverse effect of
stillbirths was 5, suggesting thereby that for every five mothers exposed to
SSDs, one would have stillbirth. Greater efforts are required to inform people
about the harmful effects of SSD consumption during pregnancy.
PMID- 26444207
TI - Cardioprotection and arrhythmias, Part 2.
PMID- 26444208
TI - [The MATRIX study].
PMID- 26444209
TI - [The PEGASUS-TIMI 54 study].
PMID- 26444210
TI - [Endomyocardial biopsy should be performed in every patient with suspected
myocarditis].
AB - The diagnosis of myocarditis is difficult because there is no pathognomonic
clinical presentation and the disease may mimic other non-inflammatory diseases.
Thus, current classifications on cardiomyopathies (e.g., the World Health
Organization and the International Society and Federation of Cardiology
[WHO/ISFC], the European Society of Cardiology [ESC], and the 2013 Expert
Myocarditis ESC Task Force) define myocarditis as an inflammatory disease of the
myocardium, which is diagnosed on endomyocardial biopsy (EMB) based upon
histological, immunological, immunohistochemical and molecular tools. This will
identify etiology, and differentiate between infectious, mainly viral, and non
infectious, immune-mediated forms. The term "inflammatory cardiomyopathy" may be
applied in biopsy-proven myocarditis with associated left, right or biventricular
dysfunction. Myocarditis may resolve spontaneously, relapse or become chronic
progressing to dilated cardiomyopathy, death or heart transplantation. The 2013
Myocarditis ESC Task Force consensus document recommends consideration of EMB and
selective coronary angiography in all patients with clinically suspected
myocarditis according to the Task Force criteria. It is recommended that EMB
analysis includes not only histology (Dallas criteria), but also immunohistology
and detection of the genome of infectious agents by molecular tools. EMB should
be performed by expert teams. The rationale for this diagnostic effort is the
availability of a wide range of immunosuppressive or immunomodulatory agents
that, as shown in systemic extracardiac autoimmune disease and in many clinical
studies, can be used in infection-negative myocarditis patients to stop or at
least stabilize chronic cardiac tissue damage mediated by the immune system, and
thus prevent fibrosis and progression to irreversible end-stage dilated
cardiomyopathy.
PMID- 26444211
TI - [Endomyocardial biopsy should be performed in selected patients with suspected
myocarditis].
AB - Endomyocardial biopsy (EMB) is the gold standard for the diagnosis of
myocarditis. Patients with clinical presentation consistent with myocarditis and
acute heart failure should undergo EMB, in particular to exclude giant-cell
myocarditis or necrotizing eosinophilic myocarditis that are life-threatening
conditions. The indication for EMB is debatable in case of suspected myocarditis
with infarct-like presentation and preserved left ventricular ejection fraction.
In fact, in this group of patients the prognosis is fairly good, and the clinical
advantage to reach a histological diagnosis by means of an invasive procedure
with potential complications such as EMB is limited. In this article we discuss
the indication for EMB in the light of current guidelines based on existing
consensus documents.
PMID- 26444212
TI - [Controversies on the role of mitochondria in coronary reperfusion damage as
potential therapeutic target].
AB - Reperfusion of an occluded coronary artery is the most effective intervention in
reducing cardiac injury which occurs as a consequence of an acute myocardial
infarction. However, reperfusion per se may exacerbate the extent of myocardial
injury which started at the onset of ischemia, thus leading to the so-called
"reperfusion injury". The published studies in the last few years provide new
hopes on the mitochondrion and its role in ischemia/reperfusion injury, through
the modulation of the mitochondrial permeability pore. After very encouraging
experimental data, two clinical trials are presented, CIRCUS and CYCLE, which
should help addressing the still outstanding question: may an intervention
targeted to decrease the permeability of the mitochondrial pore during
reperfusion reduce infarct size and improve clinical outcomes of patients with
myocardial infarction undergoing primary percutaneous coronary intervention?
PMID- 26444213
TI - [The emerging role of three-dimensional transesophageal echocardiography in
guiding the MitraClip procedure].
AB - Percutaneous edge-to-edge mitral valve repair with the MitraClip device has been
shown to be a safe and effective procedure in selected patients with moderate-to
severe mitral regurgitation. Two-dimensional transesophageal echocardiography (2D
TEE) is the primary imaging modality for guidance of the procedure. Real-time
three-dimensional (3D) TEE has recently been used as additional imaging modality
during the MitraClip procedure. In comparison with 2D TEE, 3D TEE provides
additional information in several steps of the procedure, including precise
positioning of the clip delivery system into the left atrium, correct alignment
of the clip arms perpendicular to the coaptation line and confirmation of the
correct grasping location. This review describes the relevant role of 3D TEE
imaging during the procedure, but also its limitations.
PMID- 26444214
TI - [Percutaneous treatment of chronic total occlusions: state of the art and future
perspectives].
AB - Coronary chronic total occlusions (CTO) are a frequent finding in patients
undergoing coronary angiography. However, a low percentage of patients is still
referred for percutaneous coronary intervention. The main reasons lie in the
skepticism concerning the real benefit and high technical complexity of these
interventions. In recent years, thanks to the growing operators' experience and
the introduction of new techniques and materials, the procedural success has
increased with relatively low complication rates. There is growing evidence in
recent literature that percutaneous recanalization improves symptoms and quality
of life, increases ejection fraction and prolongs survival. Appropriate patient
selection alone may involve a real clinical benefit in case of percutaneous CTO
treatment. The key to procedural success is to use the right method and the
knowledge of dedicated techniques and devices: CTO recanalization should be
performed by experienced operators, and non-CTO interventionalists should
approach these procedures only after specific training.
PMID- 26444215
TI - [A novel standard protocol of long-term follow-up shared with general
practitioners after percutaneous coronary intervention: appropriateness and
economic impact].
AB - BACKGROUND: Follow-up modalities for patients undergoing percutaneous coronary
intervention (PCI) are not well defined and standard protocols have been not
established. The purpose of this study was to assess: a) the frequency and
patterns of cardiology visits, echocardiographic examinations and stress tests
after PCI in clinical practice; b) the impact of a multidisciplinary protocol of
long-term follow-up after PCI shared with general practitioners on the
appropriateness and reduction in healthcare costs. METHODS: A total of 780
patients who underwent PCI in 2010 in two Italian hospitals were analyzed. The
number of cardiological examinations (total, routine and clinically driven)
performed during 2 years of follow-up were recorded and stratified according to
the patient's risk profile. The latter was defined according to the
multidisciplinary protocol. In addition, a simulation of the spread between
provided and necessary tests (according to the multidisciplinary protocol) was
carried out. RESULTS: The mean number of cardiological examinations per patient
provided during follow-up was 5, of which 4.4 were routine tests in asymptomatic
patients. Routine tests were performed more frequently in patients at low risk
compared to those at higher risk. By applying the multidisciplinary protocol to
the case mix and by merging clinical visit and stress test or echocardiographic
examination, a reduction of 0.87 tests per patient/year would be expected. This
reduction would result in a 39% decrease in follow-up examinations in this
specific clinical setting. CONCLUSIONS: This observational study demonstrates
that unnecessary cardiological clinical and functional tests are often performed
in long-term follow-up of patients submitted to PCI. The application of a
standard protocol of follow-up shared with general practitioners may help
avoiding unnecessary consultations, thus reducing healthcare costs.
PMID- 26444216
TI - [An unexpected culprit lesion: subclavian artery stenosis].
AB - After non-ST-elevation myocardial infarction, a 61-year-old woman underwent
coronary artery bypass grafting with left internal mammary artery (LIMA) to left
anterior descending artery combined with saphenous vein grafts to the second
obtuse marginal branch and the right coronary artery. At age 79, she was admitted
for anterior non-ST-elevation myocardial infarction. Echocardiography showed
hypokinesia of the left anterior descending territory. From the left radial
approach the LIMA graft was patent, but a critical stenosis of the proximal
subclavian artery was diagnosed and treated with stenting. The coronary
subclavian steal syndrome usually presents with effort angina but has rarely been
reported as a cause of myocardial infarction. A coronary steal syndrome should be
suspected in patients with internal mammary artery bypass with recurrence of
angina but also in case of acute coronary syndrome. When stable angina is
present, a computed tomography scan of the bypass and subclavian artery may allow
diagnosis before coronary angiography. In case of urgent coronary angiography and
undetectable culprit lesions, selective angiography of the subclavian artery may
confirm the suspicion of the coronary steal syndrome.
PMID- 26444217
TI - [The radial access approach in complex coronary anatomy: case report and
literature review].
AB - The radial artery approach has been accepted as an alternative to the traditional
femoral approach in both diagnostic and interventional procedures, including
treatment of complex coronary lesions such as chronic total occlusions.
Catheterization of the left internal mammary artery (LIMA) graft is frequently
performed through this route in order to limit catheter manipulation and avoid
dissection of the subclavian and mammary artery, a dramatic event rarely reported
in the literature. Nonetheless, indication for this approach should be carefully
evaluated, especially if an unfavorable angle of origin of the mammary artery is
present. We report the case of a patient who, following iatrogenic dissection of
the LIMA during catheterization through the left radial artery, was electively
treated with percutaneous coronary angioplasty on a complex anatomy, rather than
with high-risk redo coronary artery bypass surgery. Using a combined radial and
femoral approach, retrograde disobstruction of the left anterior descending
artery, followed by plaque debulking with rotational atherectomy through the
struts of a previously implanted stent in the left main-left circumflex artery,
was performed. Although the radial approach might be considered even for the
treatment of complex coronary anatomy subsets, appropriate use in diagnostic and
interventional settings should always be carefully evaluated.
PMID- 26444218
TI - [Position paper of the Italian Society of Invasive Cardiology (SICI-GISE) on
indications for coronary angiography in patients with stable angina].
AB - Available data suggest a steep increase in stable coronary artery disease with
age. Its prevalence reaches a peak of almost 12-14% in men aged 65-84 years with
an annual mortality ranging from 1.2% to 2.4%. The diagnosis of stable angina is
primarily based on history and therefore relies on clinical judgment. In
addition, its diagnosis can be extremely challenging because of the frequent
transition from unstable to stable angina. Current European guidelines on the
management of stable coronary artery disease give increased importance to the pre
test probability, which strongly affects the diagnostic algorithms. Imaging
techniques play a greater role in the diagnosis of stable angina than in the
past. Conversely, despite recent advances in technology and in the physiological
assessment of coronary stenosis, an ever decreasing relevance is conferred to
coronary angiography. Another difficult and controversial issue relates to the
prognostic benefit of myocardial revascularization. The aim of this position
paper is to review the most relevant clinical aspects of the European guidelines
on the management of stable coronary artery disease.
PMID- 26444219
TI - [SICI-GISE position paper on standards and guidelines for diagnostic and
catheterization laboratories].
AB - In the last few years, the activity of cath labs has undergone some notable
changes, at present largely focusing on diagnosis and invasive therapy of a broad
spectrum of cardiovascular diseases. Technological and pharmacological advances
have allowed for procedures to be performed in patients who are increasingly
complex, and cath labs have become the preferred venue for endovascular treatment
of coronary artery disease, in particular acute coronary syndrome, as well as the
treatment of structural heart disease and peripheral vascular disease. This
position paper is an update of the 1996 and 2008 versions, given the present
level of experience and the situation in Italy. It aims to provide the quality
standards required to maintain adequate conditions of know-how and safety, as
well as the structural and organizational requirements that are fundamental to
obtain the best possible use of human and technological resources. Position
papers should be a stimulus and guide for operators in the field as well as for
those who govern health policies. This should allow for an improved and more
rational allocation of cath labs in Italy, based on the real need for procedures
and an optimal distribution and organization of the cardiovascular emergency
networks while respecting the minimum standards of care.
PMID- 26444220
TI - Online Advertising for Cancer Prevention: Google Ads and Tanning Beds.
PMID- 26444222
TI - Timing of elective cesarean section and neonatal morbidity: a population-based
study.
AB - PURPOSE: To assess the incidence of neonatal complications related to gestational
age at elective cesarean section near term. METHODS: We used a population-based
dataset to compare neonatal outcomes by gestational age in uncomplicated
singleton pregnancies delivered by elective cesarean section >=37 weeks. RESULTS:
A total of 7364 mothers had an elective cesarean during 2002-2012; 343 (4.7%) at
37, 21 753 (3.8%) at 38, 3140 (2.6%) at 39, 1718 (23.3%) at 40 and 410 (5.6%) at
>=41 weeks. Infants born at a lower gestational age had a higher rate of Apgar
scores <7 (2%, 0.4%, 0.6%, 0,3%, 0.2% at 37, 38, 39, 40 and >=41 week, p =
0.013), hypoglycemia (1.5%, 1.0%, 0.8%, 0.4%, 0.5% at 37, 38, 39, 40 and >= 41
week, p = 0.012), hyperbilirubinemia (12.2%, 9.5%, 6.4%, 4.8%, 4.1% at 37, 38,
39, 40 and >= 41 week, p < 0.001), respiratory distress syndrome (5.5%, 2.2%,
1.6%, 0.5%, 0.7% at 37, 38, 39, 40 and >= 41 week, p < 0.001), and neonatal
intensive care admissions (8.7%, 2.3%, 1.9%, 1.0%, 1.7% at 37, 38, 39, 40 and >=
41 week, p < 0.001). CONCLUSIONS: Elective cesarean section at >= 39 weeks
gestation would significantly reduce neonatal complications.
PMID- 26444223
TI - Comparative analysis of redox and inflammatory properties of pristine
nanomaterials and commonly used semiconductor manufacturing nano-abrasives.
AB - Continued expansion of the nanotechnology industry has necessitated the self
assessment of manufacturing processes, specifically in regards to understanding
the health related aspects following exposure to nanomaterials. There exists a
growing concern over potential occupational exposure in the semiconductor
industry where Al2O3, CeO2 and SiO2 nanoparticles are commonly featured as part
of the chemical mechanical planarization (CMP) process. Chronic exposure to
toxicants can result not only in acute cytotoxicity but also initiation of a
chronic inflammatory state associated with diverse pathologies. In the current
investigation, pristine nanoparticles and CMP slurry formulations of Al2O3, SiO2
and CeO2 were employed to assess their ability to induce cytotoxicity,
inflammatory responses and reactive oxygen species in a mouse alveolar macrophage
cell model. The pristine nanoparticles and slurries were not intrinsically
cytotoxic and did not generate free radicals but were found to act as scavengers
in the presence of an oxidant stimulant. Al2O3 and SiO2 nanoparticles increased
levels of pro-inflammatory cytokines while pristine SiO2 nanoparticles induced
generation of F2-Isoprostanes. In co-treatment studies, the pristine
nanomaterials modulated the response to the inflammatory stimulant
lipopolysaccharide. The studies have established that pristine nanoparticles and
slurries do not impact the cells in a similar way indicating that they should not
be used as slurry substitutes in toxicity evaluations. Further, we have defined
how an alveolar cell line, which would likely be the first challenged upon
nanomaterial aerosolization, responds to diverse mixtures of nanomaterials.
Moreover, our findings reinforce the importance of using multiple analytic
methods to define the redox state of the cell following exposure to commonly used
industrial nanomaterials and toxicants.
PMID- 26444224
TI - Histological and biomechanical changes in a mouse model of venous thrombus
remodeling.
AB - BACKGROUND: Deep vein thrombosis and the risk of pulmonary embolism are
significant causes of morbidity and mortality. Much remains unclear, however,
about the mechanisms by which a venous thrombus initiates, progresses, or
resolves. In particular, there is a pressing need to characterize the evolving
mechanical properties of a venous thrombus for its mechanical integrity is
fundamental to many disease sequelae. OBJECTIVE: The primary goal of the present
study was to initiate a correlation between evolving histological changes and
biomechanical properties of venous thrombus. METHODS: We employed an inferior
vena cava ligation model in mice to obtain cylindrical samples of thrombus that
were well suited for mechanical testing and that could be explanted at multiple
times following surgery. Using uniaxial micro-mechanical testing, we collected
stress-stretch data that were then fit with a microstructurally-inspired material
model before submitting the samples to immunohistological examination. RESULTS:
We found that venous thrombus underwent a radially inward directed replacement of
fibrin with collagen between 2 weeks and 4 weeks of development, which was
accompanied by the infiltration of inflammatory and mesenchymal cells. These
histological changes correlated with a marked increase in material stiffness.
CONCLUSIONS: We demonstrated that 2 to 4 week old venous thrombus undergoes
drastic remodeling from a fibrin-dominated mesh to a collagen-dominated
microstructure and that these changes are accompanied by dramatic changes in
biomechanical behavior.
PMID- 26444221
TI - Hypothermia for Intracranial Hypertension after Traumatic Brain Injury.
AB - BACKGROUND: In patients with traumatic brain injury, hypothermia can reduce
intracranial hypertension. The benefit of hypothermia on functional outcome is
unclear. METHODS: We randomly assigned adults with an intracranial pressure of
more than 20 mm Hg despite stage 1 treatments (including mechanical ventilation
and sedation management) to standard care (control group) or hypothermia (32 to
35 degrees C) plus standard care. In the control group, stage 2 treatments (e.g.,
osmotherapy) were added as needed to control intracranial pressure. In the
hypothermia group, stage 2 treatments were added only if hypothermia failed to
control intracranial pressure. In both groups, stage 3 treatments (barbiturates
and decompressive craniectomy) were used if all stage 2 treatments failed to
control intracranial pressure. The primary outcome was the score on the Extended
Glasgow Outcome Scale (GOS-E; range, 1 to 8, with lower scores indicating a worse
functional outcome) at 6 months. The treatment effect was estimated with ordinal
logistic regression adjusted for prespecified prognostic factors and expressed as
a common odds ratio (with an odds ratio <1.0 favoring hypothermia). RESULTS: We
enrolled 387 patients at 47 centers in 18 countries from November 2009 through
October 2014, at which time recruitment was suspended owing to safety concerns.
Stage 3 treatments were required to control intracranial pressure in 54% of the
patients in the control group and in 44% of the patients in the hypothermia
group. The adjusted common odds ratio for the GOS-E score was 1.53 (95%
confidence interval, 1.02 to 2.30; P=0.04), indicating a worse outcome in the
hypothermia group than in the control group. A favorable outcome (GOS-E score of
5 to 8, indicating moderate disability or good recovery) occurred in 26% of the
patients in the hypothermia group and in 37% of the patients in the control group
(P=0.03). CONCLUSIONS: In patients with an intracranial pressure of more than 20
mm Hg after traumatic brain injury, therapeutic hypothermia plus standard care to
reduce intracranial pressure did not result in outcomes better than those with
standard care alone. (Funded by the National Institute for Health Research Health
Technology Assessment program; Current Controlled Trials number,
ISRCTN34555414.).
PMID- 26444225
TI - Storage and source of polycyclic aromatic hydrocarbons in sediments downstream of
a major coal district in France.
AB - During the 20th century, the local economy of the Upper Loire Basin (ULB) was
essentially based on industrial coal mining extraction. One of the major French
coal districts with associated urban/industrial activities and numerous
coking/gas plants were developed in the Ondaine-Furan subbasins, two tributaries
of the upper Loire main stream. To determine the compositional assemblage, the
level and the potential sources of contamination, the historical sedimentary
chronicle of the 16 US EPA priority polycyclic aromatic hydrocarbons (PAHs) has
been investigated. PAH concentrations were determined using gas
chromatography/mass spectrometry (GC/MS) in a dated core, sampled in the
Villerest flood-control reservoir located downstream of the Ondaine-Furan
corridor (OFC). The most contaminated sediments were deposited prior to 1983
(Sigma16PAHs ca. 4429-13,348 ng/g) and during flood events (Sigma16PAHs ca. 6380
ng/g - 1996 flood; 5360 ng/g - 2003 flood; 6075 ng/g - 2008 flood), especially in
medium and high molecular weight PAHs. Among them, typical pyrogenic PAHs such as
FLT, PYR, BbF and BaP were prevalent in most of the core samples. In addition,
some PAHs last decade data is available from the Loire Bretagne Water Agency and
were analyzed using high-performance liquid chromatography with postcolumn
fluorescence derivatization (HPLC/FLD). These results confirm that the most
highly contaminated sediments were found downstream of OFC (Sigma16PAHs ca. 2264
7460 ng/g). According to the observed molecular distribution, PAHs are originated
largely from high-temperature pyrolytic processes. Major sources of pyrogenic
PAHs have been emphasized by calculation of specific ratios and by comparison to
reported data. Atmospheric deposition of urban and industrial areas, wood
combustion and degraded coal tar derived from former factories of coking/gas
plants seem to be the major pyrogenic sources. Specifically, particular solid
transport conditions that can occur during major flood events lead us to
emphasize weathering of former contamination sources, such as more preserved coal
tar.
PMID- 26444226
TI - Constitutive stable DNA replication in Escherichia coli cells lacking type 1A
topoisomerase activity.
AB - Type 1A topoisomerases (topos) are ubiquitous enzymes involved in supercoiling
regulation and in the maintenance of genome stability. Escherichia coli possesses
two type 1A enzymes, topo I (topA) and topo III (topB). Cells lacking both
enzymes form very long filaments and have severe chromosome segregation and
growth defects. We previously found that RNase HI overproduction or a dnaT::aph
mutation could significantly correct these phenotypes. This leads us to
hypothesize that they were related to unregulated replication originating from R
loops, i.e. constitutive stable DNA replication (cSDR). cSDR, first observed in
rnhA (RNase HI) mutants, is characterized by its persistence for several hours
following protein synthesis inhibition and by its requirement for primosome
components, including DnaT. Here, to visualize and measure cSDR, the
incorporation of the nucleotide analog ethynyl deoxyuridine (EdU) during
replication in E. coli cells pre-treated with protein synthesis inhibitors, was
revealed by "click" labeling with Alexa Fluor((r)) 488 in fixed cells, and flow
cytometry analysis. cSDR was detected in rnhA mutants, but not in wild-type
strains, and the number of cells undergoing cSDR was significantly reduced by the
introduction of the dnaT::aph mutation. cSDR was also found in topA, double topA
topB but not in topB null cells. This result is consistent with the established
function of topo I in the inhibition of R-loop formation. Moreover, our finding
that topB rnhA mutants are perfectly viable demonstrates that topo III is not
uniquely required during cSDR. Thus, either topo I or III can provide the type 1A
topo activity that is specifically required during cSDR to allow chromosome
segregation.
PMID- 26444227
TI - Syn-Selective Synthesis of beta-Branched alpha-Amino Acids by Alkylation of
Glycine-Derived Imines with Secondary Sulfonates.
AB - A syn-selective synthesis of beta-branched alpha-amino acids has been developed
based on the alkylation of glycine imine esters with secondary sulfonates. The
potassium counterion for the enolate, the solvent, and the leaving group on the
electrophile were key levers to maximize the diasteroselectivity of the
alkylation. The optimized conditions enabled a straightforward preparation of a
number of beta-branched alpha-amino acids that can be challenging to obtain.
PMID- 26444228
TI - [Will there be new drugs for patients in Iceland 2016?[Editorial]].
PMID- 26444229
TI - [Meeting refugees[Editorial]].
PMID- 26444230
TI - [Prevalence of sport injuries, sport participation and drop out due to injury in
young adults].
AB - INTRODUCTION: Sport participation has increased during the past few decades, with
accompanying rise in sport injuries. The purpose of this study was to assess the
prevalence of sport injuries, and drop-out due to them along with possible risk
factors (hours of sports participation, sex, age, aerobic fitness and body
composition). MATERIAL AND METHODS: A retrospective, cross-sectional design was
used and the 457 participants were 17 and 23 years old. Height, weight, body fat,
lean soft tissue, bone mass, and aerobic fitness (W/kg) were measured.
Participation in sports and physical training, and the prevalence of sport
injuries and drop-out were estimated using questionnaires. RESULTS: Four hundred
and forty participants (96%) had at some time point participated in organized
sports, but 277 (63%) were no longer practicing, more commonly (p=0.058) among
girls (67.6%) than boys (58.8%). Thirty-seven (8.4%) dropped-out due to sport
injuries. Of those participating in organized sports for the past 12 months, 51%
required medical assistance at least once because of sport injuries. Multiple
regression analysis revealed 5-fold increased risk for requiring medical
assistance among those practicing more than 6 hours per week compared to those
who practiced 6 hours or less (OR=5.30, 95% CI: 3.00 to 9.42). CONCLUSION: Youth
sport injuries are a significant problem that can cause drop-out from
participation in sport. More research is needed to better understand the impact
of risk factors in order to promote prevention and ensure evidence-based
training.
PMID- 26444231
TI - [Case of the month. An elderly woman with dyspnea and stridor].
PMID- 26444232
TI - [Human Primordial Germ Cell Specification--Breakthrough In Culture and Hopes for
Therapeutic Utilization].
AB - Germ cells are the precursors to the gametes that carry genetic and epigenetic
information between human generations and generate a new individual. Because germ
cells are specified early during embryogenesis, at the time of embryo
implantation, they are inaccessible for research. Our understanding of their
biology has therefore developed slowly since their identification over one
hundred years ago. As a result of research into the properties of human and mouse
embryonic stem cells and primordial germ cells, scientists have now succeeded in
efficiently generating human primordial germ cells in culture by embryonic stem
cell and induced pluripotent stem cell culture. In this review we will discuss
the state of our knowledge of human primordial germ cells and how research into
the pluripotent properties of human and mouse embryonic germ cells has led to
this breakthrough. In addition we will discuss the possible utilization of a cell
culture system of human primordial germ cells for research into and treatment of
germ cell related abnormalities.
PMID- 26444233
TI - Evolution: An avian explosion.
PMID- 26444234
TI - Erratum: Arithmetic and local circuitry underlying dopamine prediction errors.
PMID- 26444235
TI - Biological techniques: Kidney tissue grown from induced stem cells.
PMID- 26444236
TI - Kidney organoids from human iPS cells contain multiple lineages and model human
nephrogenesis.
AB - The human kidney contains up to 2 million epithelial nephrons responsible for
blood filtration. Regenerating the kidney requires the induction of the more than
20 distinct cell types required for excretion and the regulation of pH, and
electrolyte and fluid balance. We have previously described the simultaneous
induction of progenitors for both collecting duct and nephrons via the directed
differentiation of human pluripotent stem cells. Paradoxically, although both are
of intermediate mesoderm in origin, collecting duct and nephrons have distinct
temporospatial origins. Here we identify the developmental mechanism regulating
the preferential induction of collecting duct versus kidney mesenchyme
progenitors. Using this knowledge, we have generated kidney organoids that
contain nephrons associated with a collecting duct network surrounded by renal
interstitium and endothelial cells. Within these organoids, individual nephrons
segment into distal and proximal tubules, early loops of Henle, and glomeruli
containing podocytes elaborating foot processes and undergoing vascularization.
When transcription profiles of kidney organoids were compared to human fetal
tissues, they showed highest congruence with first trimester human kidney.
Furthermore, the proximal tubules endocytose dextran and differentially apoptose
in response to cisplatin, a nephrotoxicant. Such kidney organoids represent
powerful models of the human organ for future applications, including
nephrotoxicity screening, disease modelling and as a source of cells for therapy.
PMID- 26444237
TI - A comprehensive phylogeny of birds (Aves) using targeted next-generation DNA
sequencing.
AB - Although reconstruction of the phylogeny of living birds has progressed
tremendously in the last decade, the evolutionary history of Neoaves--a clade
that encompasses nearly all living bird species--remains the greatest unresolved
challenge in dinosaur systematics. Here we investigate avian phylogeny with an
unprecedented scale of data: >390,000 bases of genomic sequence data from each of
198 species of living birds, representing all major avian lineages, and two
crocodilian outgroups. Sequence data were collected using anchored hybrid
enrichment, yielding 259 nuclear loci with an average length of 1,523 bases for a
total data set of over 7.8 * 10(7) bases. Bayesian and maximum likelihood
analyses yielded highly supported and nearly identical phylogenetic trees for all
major avian lineages. Five major clades form successive sister groups to the rest
of Neoaves: (1) a clade including nightjars, other caprimulgiforms, swifts, and
hummingbirds; (2) a clade uniting cuckoos, bustards, and turacos with pigeons,
mesites, and sandgrouse; (3) cranes and their relatives; (4) a comprehensive
waterbird clade, including all diving, wading, and shorebirds; and (5) a
comprehensive landbird clade with the enigmatic hoatzin (Opisthocomus hoazin) as
the sister group to the rest. Neither of the two main, recently proposed Neoavian
clades--Columbea and Passerea--were supported as monophyletic. The results of our
divergence time analyses are congruent with the palaeontological record,
supporting a major radiation of crown birds in the wake of the Cretaceous
Palaeogene (K-Pg) mass extinction.
PMID- 26444238
TI - Control of REM sleep by ventral medulla GABAergic neurons.
AB - Rapid eye movement (REM) sleep is a distinct brain state characterized by
activated electroencephalogram and complete skeletal muscle paralysis, and is
associated with vivid dreams. Transection studies by Jouvet first demonstrated
that the brainstem is both necessary and sufficient for REM sleep generation, and
the neural circuits in the pons have since been studied extensively. The medulla
also contains neurons that are active during REM sleep, but whether they play a
causal role in REM sleep generation remains unclear. Here we show that a
GABAergic (gamma-aminobutyric-acid-releasing) pathway originating from the
ventral medulla powerfully promotes REM sleep in mice. Optogenetic activation of
ventral medulla GABAergic neurons rapidly and reliably initiated REM sleep
episodes and prolonged their durations, whereas inactivating these neurons had
the opposite effects. Optrode recordings from channelrhodopsin-2-tagged ventral
medulla GABAergic neurons showed that they were most active during REM sleep
(REMmax), and during wakefulness they were preferentially active during eating
and grooming. Furthermore, dual retrograde tracing showed that the rostral
projections to the pons and midbrain and caudal projections to the spinal cord
originate from separate ventral medulla neuron populations. Activating the
rostral GABAergic projections was sufficient for both the induction and
maintenance of REM sleep, which are probably mediated in part by inhibition of
REM-suppressing GABAergic neurons in the ventrolateral periaqueductal grey. These
results identify a key component of the pontomedullary network controlling REM
sleep. The capability to induce REM sleep on command may offer a powerful tool
for investigating its functions.
PMID- 26444239
TI - The genetic sex-determination system predicts adult sex ratios in tetrapods.
AB - The adult sex ratio (ASR) has critical effects on behaviour, ecology and
population dynamics, but the causes of variation in ASRs are unclear. Here we
assess whether the type of genetic sex determination influences the ASR using
data from 344 species in 117 families of tetrapods. We show that taxa with female
heterogamety have a significantly more male-biased ASR (proportion of males: 0.55
+/- 0.01 (mean +/- s.e.m.)) than taxa with male heterogamety (0.43 +/- 0.01). The
genetic sex-determination system explains 24% of interspecific variation in ASRs
in amphibians and 36% in reptiles. We consider several genetic factors that could
contribute to this pattern, including meiotic drive and sex-linked deleterious
mutations, but further work is needed to quantify their effects. Regardless of
the mechanism, the effects of the genetic sex-determination system on the adult
sex ratio are likely to have profound effects on the demography and social
behaviour of tetrapods.
PMID- 26444241
TI - Peptoid nanosheets exhibit a new secondary-structure motif.
AB - A promising route to the synthesis of protein-mimetic materials that are capable
of complex functions, such as molecular recognition and catalysis, is provided by
sequence-defined peptoid polymers--structural relatives of biologically occurring
polypeptides. Peptoids, which are relatively non-toxic and resistant to
degradation, can fold into defined structures through a combination of sequence
dependent interactions. However, the range of possible structures that are
accessible to peptoids and other biological mimetics is unknown, and our ability
to design protein-like architectures from these polymer classes is limited. Here
we use molecular-dynamics simulations, together with scattering and microscopy
data, to determine the atomic-resolution structure of the recently discovered
peptoid nanosheet, an ordered supramolecular assembly that extends
macroscopically in only two dimensions. Our simulations show that nanosheets are
structurally and dynamically heterogeneous, can be formed only from peptoids of
certain lengths, and are potentially porous to water and ions. Moreover, their
formation is enabled by the peptoids' adoption of a secondary structure that is
not seen in the natural world. This structure, a zigzag pattern that we call a
Sigma('sigma')-strand, results from the ability of adjacent backbone monomers to
adopt opposed rotational states, thereby allowing the backbone to remain linear
and untwisted. Linear backbones tiled in a brick-like way form an extended two
dimensional nanostructure, the Sigma-sheet. The binary rotational-state motif of
the Sigma-strand is not seen in regular protein structures, which are usually
built from one type of rotational state. We also show that the concept of
building regular structures from multiple rotational states can be generalized
beyond the peptoid nanosheet system.
PMID- 26444242
TI - Erratum: A positional Toll receptor code directs convergent extension in
Drosophila.
PMID- 26444243
TI - Prevalence of Obesity and Overweight in an Indigenous Population in Central
Brazil: A Population-Based Cross-Sectional Study.
AB - OBJECTIVE: To estimate the prevalence of obesity and overweight and associated
factors in indigenous people of the Jaguapiru village in Central Brazil. METHODS:
We conducted a population-based cross-sectional study between January 2009 and
July 2011 in the adult native population of the Jaguapiru village, Central
Brazil. Sociodemographic and lifestyle data were obtained; anthropometric
measures, arterial blood pressure, and blood glucose were measured. The
independent variables were tested by Poisson regression, and the interactions
between them were analyzed. RESULTS: 1,608 indigenous people (982 females, mean
age 37.7 +/- 15.1 years) were included. The prevalence of obesity was 23.2% (95%
CI 20.9-25.1%). Obesity was more prevalent among 40- to 49-year-old and
overweight among 50- to 59-year-old persons. Obesity was positively associated
with female sex, higher income, and hypertension. Among indigenous people,
interactions were found with hypertension and sedentary lifestyle - hypertension
in males and sedentary lifestyle in females. CONCLUSIONS: The prevalence of
obesity and overweight in indigenous people of the Jaguapiru village is high.
Males as well as hypertensive and higher family income individuals have higher
rates. Sedentary lifestyle and hypertension leverage the rates of obesity.
Prevention and adequate public health policies can be critical for the control of
excess weight and its comorbidities among Brazilian indigenous people.
PMID- 26444240
TI - Alternative transcription initiation leads to expression of a novel ALK isoform
in cancer.
AB - Activation of oncogenes by mechanisms other than genetic aberrations such as
mutations, translocations, or amplifications is largely undefined. Here we report
a novel isoform of the anaplastic lymphoma kinase (ALK) that is expressed in ~11%
of melanomas and sporadically in other human cancer types, but not in normal
tissues. The novel ALK transcript initiates from a de novo alternative
transcription initiation (ATI) site in ALK intron 19, and was termed ALK(ATI). In
ALK(ATI)-expressing tumours, the ATI site is enriched for H3K4me3 and RNA
polymerase II, chromatin marks characteristic of active transcription initiation
sites. ALK(ATI) is expressed from both ALK alleles, and no recurrent genetic
aberrations are found at the ALK locus, indicating that the transcriptional
activation is independent of genetic aberrations at the ALK locus. The ALK(ATI)
transcript encodes three proteins with molecular weights of 61.1, 60.8 and 58.7
kilodaltons, consisting primarily of the intracellular tyrosine kinase domain.
ALK(ATI) stimulates multiple oncogenic signalling pathways, drives growth-factor
independent cell proliferation in vitro, and promotes tumorigenesis in vivo in
mouse models. ALK inhibitors can suppress the kinase activity of ALK(ATI),
suggesting that patients with ALK(ATI)-expressing tumours may benefit from ALK
inhibitors. Our findings suggest a novel mechanism of oncogene activation in
cancer through de novo alternative transcription initiation.
PMID- 26444244
TI - High-Intensity Induction in the Elderly.
PMID- 26444245
TI - Supramolecular Macrocyclic Pd(II) and Pt(II) Squares and Rectangles with
Aryldithiolate Ligands and their Excellent Catalytic Activity in Suzuki C-C
Coupling Reaction.
AB - Addition of 1,4-benezenedithiol and 4,4'-biphenyldithiol to M(OTf)2 (M = cis
[Pt(PEt3)2](2+) or cis-[Pd(dppe)](2+)) (dppe = 1,2-bis(diphenylphosphino)ethane)
gave self-assembled tetranuclear complexes [M2{S(C6H4)nS}]2(OTf)4 (n = 1, 2). The
same reaction with 1,4-benezenedimethanethiol yielded octanuclear supramolecular
coordination complexes (SCC) [M2{SCH2C6H4CH2S}]4(OTf)8. These complexes were
characterized by NMR, mass, and UV-vis spectroscopies, cyclic voltammetry, as
well as density functional theory studies and represent the first examples of
SCCs constructed by thiolate groups and square-planar metal ions. The rectangular
shape of tetranuclear complexes and square shape of octanuclear complex are
confirmed by single-crystal structures and computational studies. The palladium
complexes showed excellent catalytic activity in Suzuki C-C cross-coupling
reactions with high turnover numbers (2 * 10(7)), even with low catalyst loading.
PMID- 26444246
TI - Anchoring High-Concentration Oxygen Vacancies at Interfaces of CeO(2-x)/Cu toward
Enhanced Activity for Preferential CO Oxidation.
AB - Catalysts are urgently needed to remove the residual CO in hydrogen feeds through
selective oxidation for large-scale applications of hydrogen proton exchange
membrane fuel cells. We herein propose a new methodology that anchors high
concentration oxygen vacancies at interface by designing a CeO2-x/Cu hybrid
catalyst with enhanced preferential CO oxidation activity. This hybrid catalyst,
with more than 6.1% oxygen vacancies fixed at the favorable interfacial sites,
displays nearly 100% CO conversion efficiency in H2-rich streams over a broad
temperature window from 120 to 210 degrees C, strikingly 5-fold wider than that
of conventional CeO2/Cu (i.e., CeO2 supported on Cu) catalyst. Moreover, the
catalyst exhibits a highest cycling stability ever reported, showing no
deterioration after five cycling tests, and a super long-time stability beyond
100 h in the simulated operation environment that involves CO2 and H2O. On the
basis of an arsenal of characterization techniques, we clearly show that the
anchored oxygen vacancies are generated as a consequence of electron donation
from metal copper atoms to CeO2 acceptor and the subsequent reverse spillover of
oxygen induced by electron transfer in well controlled nanoheterojunction. The
anchored oxygen vacancies play a bridging role in electron capture or transfer
and drive molecule oxygen into active oxygen species to interact with the CO
molecules adsorbed at interfaces, thus leading to an excellent preferential CO
oxidation performance. This study opens a window to design a vast number of high
performance metal-oxide hybrid catalysts via the concept of anchoring oxygen
vacancies at interfaces.
PMID- 26444247
TI - Development of an Optical Nanosensor Incorporating a pH-Sensitive Quencher Dye
for Potassium Imaging.
AB - One of the key challenges in the design of a sensor for measuring extracellular
changes in potassium concentration is selectivity against the competing cation,
sodium. Here, we present an optode-based nanosensor selective to potassium ions,
owing to the addition of a pH-sensitive quencher molecule paired with a static
fluorophore. The nanosensor was fabricated using emulsification and characterized
in solution by absorbance and fluorescence spectroscopy. The resulting nanosensor
detected potassium with nearly 1 order of magnitude higher selectivity compared
to our chromoionophore-based optode nanosensors. In addition to the improved
selectivity, the nanosensor has the following properties required for
measurements in a biological environment: (1) a physiologically relevant dynamic
range, (2) response to potassium ions at a physiological ionic strength, and (3)
response to serum potassium in the presence of fouling biological components. The
potassium nanosensor described in this study is envisioned to have application in
cellular imaging and drug screening.
PMID- 26444248
TI - Labdane and Clerodane Diterpenoids from Colophospermum mopane.
AB - Five labdane (1-5), an isolabdane (6), and five clerodane diterpenoids (7-11),
were isolated from seeds, husks, and leaves of Colophospermum mopane. Compounds 1
3 and 6-9 are new, and their structures were elucidated by means of physical data
analysis (1D and 2D NMR, HRESIMS). The absolute configurations of 1, 7, and 10
were determined by single-crystal X-ray diffraction with Cu Kalpha radiation. For
compounds 2 and 6, the absolute configurations were established by the modified
Mosher's method and corroborated by comparison of experimental and calculated
electronic circular dichroism spectra of their 3-p-bromobenzoate derivatives. The
crude extracts and compounds were evaluated for antimicrobial activity. The leaf
extract was the most active against Staphylococcus aureus (125 MUg/mL). Compound
11 showed the best inhibitory activity, with minimum inhibitory values of 15.6
MUg/mL against Escherichia coli and Staphylococcus aureus and 31.3 MUg/mL against
Enterococcus faecalis.
PMID- 26444249
TI - Synthesis of N-Aryl beta-Amino Alcohols by Trifluoroacetic Acid Promoted
Multicomponent Coupling of Aziridines, Arynes, and Water.
AB - A transition-metal-free, three-component coupling involving N-substituted
aziridines, arynes, and water promoted by trifluoroacetic acid (TFA) has been
reported. The reaction furnished medicinally important N-aryl beta-amino alcohol
derivatives in moderate to good yields. In addition, the use of azetidines in
this reaction afforded N-aryl gamma-amino alcohol derivatives.
PMID- 26444250
TI - Designing a "Flatter" ExBox(4+) Analogue.
AB - Analogues of ExBox(4+) 1 are proposed that possess triaryl fragments that are
nearly flat. These two new hosts are predicted by density functional theory
(omegaB97X-D/6-311G(d,p)) to bind five small linear acenes more tightly than does
1. The "flatter" triaryl fragments provide a less congested interior along with
improved pi-pi-stacking between these hosts and guests.
PMID- 26444251
TI - Morphologic Features Suggestive of Endometriosis in Nondiagnostic Peritoneal
Biopsies.
AB - Endometriosis is a common disorder that causes significant morbidity from
dysmenorrhea, pelvic pain, and subfertility. Establishment of a definitive
diagnosis has important therapeutic implications; however, only approximately 50%
of biopsies of laparoscopically suspicious areas provide a diagnosis of
endometriosis. Histologic criteria for diagnosis require the presence of
endometrial glands or endometrial-type stroma. We hypothesize that other
frequently present, but nondiagnostic, histologic features of endometriosis
suggest its presence in patients with nondiagnostic peritoneal biopsies. We
performed a retrospective clinicopathologic study of morphologic and
immunohistochemical features that may improve the histologic diagnosis of
endometriosis on laparoscopic peritoneal biopsies. We compared diagnostic (n=88)
and nondiagnostic (n=54) peritoneal biopsies from pathologically confirmed
endometriosis cases with negative peritoneal biopsies (n=84) from early-stage
gynecologic cancer cases. Statistical analysis utilized the Fisher exact test.
Multiple morphologic features were significantly increased in nondiagnostic
biopsies from patients with endometriosis in comparison with those from negative
controls, including foamy macrophages (P=0.0001) and submesothelial stromal
clusters (SSCs) (P=0.0008). SSCs ranged from subtle aggregates of spindle cells
to nodules of whorled spindle cells with small vessels and extravasated red blood
cells resembling stromal endometriosis. Immunohistochemical studies confirmed
that ER and CD10-positive SSCs were present in a greater proportion of both
nondiagnostic and diagnostic peritoneal biopsies and at a greater number of
lesions per biopsy. The overall histologic detection rate of peritoneal biopsies
for endometriosis was 62.0%, and inclusion of SSCs with or without foamy
macrophages in the diagnostic criteria appreciably increased this rate to between
72.5% and 76.8%. We describe SSCs, which appear to be an early or less developed
form of stromal endometriosis, and, when included in the diagnostic criteria,
improve the histologic detection rate of endometriosis in peritoneal biopsies.
PMID- 26444252
TI - Coexistence of Microcystic Stromal Tumor of the Ovary With Mutation of beta
Catenin and Contralateral Mucinous Cystadenoma.
PMID- 26444253
TI - Analysis of MDM2 Amplification in 43 Endometrial Stromal Tumors: A Potential
Diagnostic Pitfall.
AB - MDM2 amplification is known to occur in a variety of neoplasms and its detection
by fluorescence in situ hybridization is helpful in distinguishing well
differentiated and dedifferentated liposarcoma from classic lipoma. We recently
evaluated a mesenteric mass initially diagnosed as dedifferentiated liposarcoma,
largely due to the neoplasm's myxoid morphology and MDM2 expression by
immunohistochemistry, from a 46-yr-old woman with a history of uterine low-grade
endometrial stromal sarcoma (LG-ESS) with a JAZF1 rearrangement. Our workup of
the mesenteric mass revealed a JAZF1 rearrangement and a revised diagnosis of
metastatic LG-ESS with myxoid change was rendered. Retrospective testing of the
mesenteric mass was negative for MDM2 amplification, an uncommon, but known
diagnostic pitfall in MDM2 expression by immunohistochemistry. As MDM2
amplification is not specific for the diagnosis of liposarcoma, we investigated
its occurrence in 43 cases of endometrial stromal tumors: 14 uterine LG-ESS, 11
metastatic or recurrent uterine LG-ESS, 8 undifferentiated uterine sarcomas, 5
endometrial stromal nodules, and 4 high-grade ESS with YHWAE rearrangement. In
addition, 40 of the 43 cases had previously undergone fluorescence in situ
hybridization analysis of JAZF1, PHF1, and YHWAE. Two of the 43 cases (5%) had
MDM2 amplification: one was a uterine LG-ESS (JAZF1 rearrangement) and the other
was a undifferentiated uterine sarcoma (polysomy intact JAZF1, PHF1, and YHWAE),
both metastatic to the lung. Both cases positive for MDM2 amplification showed
MDM2 expression by immunohistochemistry. At last follow-up, both patients had
died of disease (19 and 60 mo). Our study is the first to demonstrate MDM2
amplification in endometrial stromal tumor. Awareness of MDM2 amplification in
endometrial stromal tumor is critical; particularly in locations more common to
liposarcoma, to avoid diagnostic errors.
PMID- 26444254
TI - The relationship between serum levels of total bilirubin and coronary plaque
vulnerability.
AB - OBJECTIVES: Previous studies have reported that serum total bilirubin provides
some protection against coronary artery disease (CAD); however, the relationship
between serum levels of total bilirubin and culprit/target plaque vulnerability
in patients with CAD remains unclear. In this study, we investigated the
association between total bilirubin and tissue characterization of coronary
plaque in patients with CAD. METHODS: We enrolled 85 consecutive patients with
CAD who underwent coronary angiography and intravascular ultrasound analyses [45
with acute coronary syndrome (ACS); 40 with stable angina pectoris (SAP)], and 45
age-matched participants served as the control group. Serum levels of total
bilirubin in all participants were measured. The stability of the coronary plaque
was compared between the ACS group and the SAP group, and the relationship
between serum levels of total bilirubin and the features of coronary plaque was
analyzed. RESULTS: Serum levels of total bilirubin in the ACS group were
significantly lower than those in the SAP and control groups (P<0.01). Serum
levels of total bilirubin were positively associated with fibrous plaques
(r=0.386, P<0.001), whereas they were negatively associated with plaque burden
(r=-0.413, P<0.001), lipid plaque (r=-0.419, P<0.001), and remodeling index (r=
0.275, P<0.05). Furthermore, an independent association between serum levels of
total bilirubin and lipid-rich plaques (odds ratio, 0.78; 95% confidence
interval, 0.64-0.95) was observed. CONCLUSION: Serum total bilirubin levels were
found to be inversely associated with coronary plaque vulnerability, and
decreased serum levels of total bilirubin may be an important factor for coronary
lipid plaque formation, which contributes to the pathogenesis of CAD.
PMID- 26444255
TI - Transition strategies from cangrelor to oral platelet P2Y12 receptor antagonists.
AB - Cangrelor is the first parenteral antagonist of the platelet P2Y12 receptor. This
direct-acting antagonist of the platelet P2Y12 receptor should be considered an
adjunct to a percutaneous coronary intervention in patients who have not been
adequately pretreated with platelet P2Y12 receptor antagonists at the time of the
procedure. The use of cangrelor requires transition to an oral platelet P2Y12
receptor antagonist. Transition strategies have been developed on the basis of
pharmacologic characteristics of platelet P2Y12 receptor antagonists, results of
pharmacodynamic studies, and results from clinical trials. Cangrelor blocks the
binding to the platelet P2Y12 receptor of the active metabolite of the
thienopyridines, clopidogrel and prasugrel. The active metabolite of
thienopyridines is present in blood for a short interval after administration.
For this reason, clopidogrel should be administered after cangrelor is stopped.
Prasugrel can be administered at the end of the cangrelor infusion or up to 30
min before cangrelor is stopped. Ticagrelor is also a reversible direct-acting
antagonist of the platelet P2Y12 receptor. Because there is no interaction
between ticagrelor and cangrelor, ticagrelor can be administered before or during
the infusion of cangrelor.
PMID- 26444256
TI - Impacts of Silver Nanoparticles on a Natural Estuarine Plankton Community.
AB - Potential effects of metal nanoparticles on aquatic organisms and food webs are
hard to predict from the results of single-species tests under controlled
laboratory conditions, and more realistic exposure experiments are rarely
conducted. We tested whether silver nanoparticles (Ag NPs) had an impact on
zooplankton grazing on their prey, specifically phytoplankton and
bacterioplankton populations. If Ag NPs directly reduced the abundance of prey,
thereby causing the overall rate of grazing by their predators to decrease, a
cascading effect on a planktonic estuarine food web would be seen. Our results
show that the growth rates of both phytoplankton and bacterioplankton populations
were significantly reduced by Ag NPs at concentrations of >=500 MUg L(-1). At the
same time, grazing rates on these populations tended to decline with exposure to
Ag NPs. Therefore, Ag NPs did not cause a cascade of effects through the food web
but impacted a specific trophic level. Photosynthetic efficiency of the
phytoplankton was significantly reduced at Ag NPs concentrations of >=500 MUg L(
1). These effects did not occur at relatively low concentrations of Ag that are
often toxic to single species of bacteria and other organisms, suggesting that
the impacts of Ag NP exposure may not be apparent at environmentally relevant
concentrations due to compensatory processes at the community level.
PMID- 26444257
TI - Genetic diversity of variants involved in drug response and metabolism in Sri
Lankan populations: implications for clinical implementation of pharmacogenomics.
AB - BACKGROUND: Interpopulation differences in drug responses are well documented,
and in some cases they correspond to differences in the frequency of associated
genetic markers. Understanding the diversity of genetic markers associated with
drug response across different global populations is essential to infer
population rates of drug response or risk for adverse drug reactions, and to
guide implementation of pharmacogenomic testing. Sri Lanka is a culturally and
linguistically diverse nation, but little is known about the population genetics
of the major Sri Lankan ethnic groups. The objective of this study was to
investigate the diversity of pharmacogenomic variants in the major Sri Lankan
ethnic groups. METHODS: We examined the allelic diversity of more than 7000
variants in genes involved in drug biotransformation and response in the three
major ethnic populations of Sri Lanka (Sinhalese, Sri Lankan Tamils, and Moors),
and compared them with other South Asian, South East Asian, and European
populations using Wright's Fixation Index, principal component analysis, and
STRUCTURE analysis. RESULTS: We observed overall high levels of similarity within
the Sri Lankan populations (median FST=0.0034), and between Sri Lankan and other
South Asian populations (median FST=0.0064). Notably, we observed substantial
differentiation between Sri Lankan and European populations for important
pharmacogenomic variants related to warfarin (VKORC1 rs9923231) and clopidogrel
(CYP2C19 rs4986893) response. CONCLUSION: These data expand our understanding of
the population structure of Sri Lanka, provide a resource for pharmacogenomic
research, and have implications for the clinical use of genetic testing of
pharmacogenomic variants in these populations.
PMID- 26444259
TI - Early group bias in the Faroe Islands: Cultural variation in children's group
based reasoning.
AB - Recent developmental research demonstrates that group bias emerges early in
childhood. However, little is known about the extent to which bias in minimal
(i.e., arbitrarily assigned) groups varies with children's environment and
experience, and whether such bias is universal across cultures. In this study,
the development of group bias was investigated using a minimal groups paradigm
with 46 four- to six-year-olds from the Faroe Islands. Children observed in-group
and out-group members exhibiting varying degrees of prosocial behaviour
(egalitarian or stingy sharing). Children did not prefer their in-group in the
pretest, but a pro-in-group and anti-out-group sentiment emerged in both
conditions in the posttest. Faroese children's response patterns differ from
those of American children [Schug, M. G., Shusterman, A., Barth, H., & Patalano,
A. L. (2013). Minimal-group membership influences children's responses to novel
experience with group members. Developmental Science, 16(1), 47-55], suggesting
that intergroup bias shows cultural variation even in a minimal groups context.
PMID- 26444258
TI - Wheat WCBP1 encodes a putative copper-binding protein involved in stripe rust
resistance and inhibition of leaf senescence.
AB - BACKGROUND: Stripe rust, a highly destructive foliar disease of wheat (Triticum
aestivum), causes severe losses, which may be accompanied by reduced
photosynthetic activity and accelerated leaf senescence. METHODS: We used
suppression subtractive hybridization (SSH) to examine the mechanisms of
resistance in the resistant wheat line L693 (Reg. No. GP-972, PI 672538), which
was derived from a lineage that includes a wide cross between common and
Thinopyrum intermedium. Sequencing of an SSH cDNA library identified 112
expressed sequence tags. RESULTS: In silico mapping placed one of these tags
[GenBank: JK972238] on chromosome 1A. Primers based on [GenBank: JK972238]
amplified a polymorphic band, which co-segregated with YrL693. We cloned a
candidate gene encoding wheat copper-binding protein (WCBP1) by amplifying the
polymorphic region, and we mapped WCBP1 to a 0.64 cM genetic interval.
Brachypodium, rice, and sorghum have genes and genomic regions syntenic to this
region. DISCUSSION: Sequence analysis suggested that the resistant WCBP1 allele
might have resulted from a deletion of 36-bp sequence of the wheat genomic
sequence, rather than direct transfer from Th. intermedium. qRT-PCR confirmed
that WCBP1 expression changes in response to pathogen infection. CONCLUSIONS: The
unique chromosomal location and expression mode of WCBP1 suggested that WCBP1 is
the putative candidate gene of YrL693, which was involved in leaf senescence and
photosynthesis related to plant responses to stripe rust infection during the
grain-filling stage.
PMID- 26444260
TI - Effects of smoking and alcohol use on neurocognitive functioning in heavy
drinking, HIV-positive men who have sex with men.
AB - High rates of cognitive impairment persist in human immunodeficiency virus (HIV)
infection, despite improved health outcomes and reduced mortality through
widespread use of antiretroviral therapy (ART). Heavy alcohol use and cigarette
smoking are potential contributors to neurocognitive impairment in people living
with HIV (PLWH), yet few studies have examined their influence concurrently. Here
we investigated the effects of self-reported alcohol use and smoking on learning,
memory, processing speed, verbal fluency, and executive function in 124 HIV
positive men who have sex with men [age (mean +/- SD) = 42.8 +/- 10.4 years],
engaged with medical care. All participants were heavy drinkers. Duration of HIV
infection averaged 9.9 +/- 7.6 years, and 92.7% were on a stable ART regimen.
Participants completed a neuropsychological battery and assessment of past 30-day
substance use. Average number of drinks per drinking day (DPDD) was 5.6 +/- 3.5,
and 33.1% of participants were daily smokers. Rates of neurocognitive impairment
were the highest in learning (50.8%), executive function (41.9%), and memory
(38.0%). Multiple regression models tested DPDD and smoking status as predictors
of neurocognitive performance, controlling for age and premorbid intelligence.
Smoking was significantly, negatively related to verbal learning (p = .046) and
processing speed (p = .001). DPDD was a significant predictor of learning (p =
.047) in a model that accounted for the interaction of DPDD and smoking status.
As expected, premorbid intelligence significantly predicted all neurocognitive
scores (ps < .01), and older age was associated with slower processing speed (ps
< .01). In conclusion, smoking appears to be associated with neurocognitive
functioning deficits in PLWH beyond the effects of heavy drinking, aging, and
premorbid intelligence. Smoking cessation interventions have the potential to be
an important target for improving functional outcomes in heavy drinking PLWH.
PMID- 26444261
TI - Cultural competency training of GP Registrars-exploring the views of GP
Supervisors.
AB - INTRODUCTION: An equitable multicultural society requires General Practitioners
(GPs) to be proficient in providing health care to patients from diverse
backgrounds. This requires a certain set of attitudes, knowledge and skills known
as cultural competence. While training in cultural competence is an important
part of the Australian GP Registrar training curriculum, it is unclear who
provides this training apart from in Aboriginal and Torres Strait Islander
training posts. The majority of Australian GP Registrar training takes place in a
workplace setting facilitated by the GP Supervisor. In view of the central role
of GP Supervisors, their views on culturally competent practice, and their role
in its development in Registrars, are important to ascertain. METHODS: We
conducted 14 semi-structured interviews with GP Supervisors. These were
audiotaped, transcribed verbatim and thematically analyzed using an iterative
approach. RESULTS: The Supervisors interviewed frequently viewed cultural
competence as adequately covered by using patient-centered approaches. The
Supervisor role in promoting cultural competence of Registrars was affirmed,
though training was noted to occur opportunistically and focused largely on
patient-centered care rather than health disparities. CONCLUSION: Formal training
for both Registrars and Supervisors may be beneficial not only to develop a
deeper understanding of cultural competence and its relevance to practice but
also to promote more consistency in training from Supervisors in the area,
particularly with respect to self-reflection, non-conscious bias and utilizing
appropriate cultural knowledge without stereotyping and assumption-making.
PMID- 26444262
TI - Conservation analysis of sequences flanking the testis-determining gene Sry in 17
mammalian species.
AB - BACKGROUND: Sex determination in mammals requires expression of the Y-linked gene
Sry in the bipotential genital ridges of the XY embryo. Even minor delay of the
onset of Sry expression can result in XY sex reversal, highlighting the need for
accurate gene regulation during sex determination. However, the location of
critical regulatory elements remains unknown. Here, we analysed Sry flanking
sequences across many species, using newly available genome sequences and
computational tools, to better understand Sry's genomic context and to identify
conserved regions predictive of functional roles. METHODS: Flanking sequences
from 17 species were analysed using both global and local sequence alignment
methods. Multiple motif searches were employed to characterise common motifs in
otherwise unconserved sequence. RESULTS: We identified position-specific
conservation of binding motifs for multiple transcription factor families,
including GATA binding factors and Oct/Sox dimers. In contrast with the landscape
of extremely low sequence conservation around the Sry coding region, our analysis
highlighted a strongly conserved interval of ~106 bp within the Sry promoter
(which we term the Sry Proximal Conserved Interval, SPCI). We further report that
inverted repeats flanking murine Sry are much larger than previously recognised.
CONCLUSIONS: The unusually fast pace of sequence drift on the Y chromosome
sharpens the likely functional significance of both the SPCI and the identified
binding motifs, providing a basis for future studies of the role(s) of these
elements in Sry regulation.
PMID- 26444263
TI - PIPEQ-OS--an instrument for on-site measurements of the experiences of inpatients
at psychiatric institutions.
AB - BACKGROUND: The Psychiatric Inpatient Patient Experience Questionnaire (PIPEQ)
was developed for post-discharge measurements of experiences, but the low
response rates associated with post-discharge surveys restrict their usefulness.
A new questionnaire was developed based on the PIPEQ for on-site measurements of
patient experiences: the PIPEQ-OS. The aim of this study was to psychometrically
test the PIPEQ-OS using data from a nationally representative survey conducted in
Norway in 2014. METHODS: Data were collected using a nationally representative
patient-experience survey; 25% of the institutions in each of the 4 health
regions in Norway were randomly selected, yielding a total of 26 institutions.
The PIPEQ-OS questionnaire was completed by patients on-site on an agreed day in
week 37 of 2014. Item missing and ceiling effects were assessed, and factor
analysis was used to assess the structure of the items included in the PIPEQ-OS.
The scales were tested for internal consistency reliability, test-retest
reliability and construct validity. RESULTS: The initial sample comprised 857
patients. Of these, 60 were excluded for ethical reasons and 57 were excluded
because they were absent on the day of the survey. Of the remaining 740 patients,
552 (74.6% of the included population) returned the questionnaire. Low levels of
missing or "not applicable" responses were found for 18 of the 21 items (<20%),
and 20 of 21 items were below the ceiling-effect criterion. Psychometric testing
identified three scales: structure and facilities (six items), patient-centred
interaction (six items) and outcomes (five items). All scales met the criterion
of 0.7 for Cronbach's alpha (range: 0.79-0.91) and test-retest reliability
(range: 0.83-0.84). The construct validity of the scales was supported by 14 of
15 significant associations with variables known to be related to psychiatric
inpatient experiences. CONCLUSIONS: The PIPEQ-OS comprises three scales with
satisfactory internal consistency reliability and construct validity. This
instrument can be used for on-site assessments of psychiatric inpatient patient
experiences, but further research is needed to evaluate its usefulness as basis
for external quality indicators.
PMID- 26444264
TI - Development and field evaluation of the sentinel mosquito arbovirus capture kit
(SMACK).
AB - BACKGROUND: Although sentinel animals are used successfully throughout the world
to monitor arbovirus activity, ethical considerations and cross-reactions in
serological assays highlight the importance of developing viable alternatives.
Here we outline the development of a passive sentinel mosquito arbovirus capture
kit (SMACK) that allows for the detection of arboviruses on honey-baited nucleic
acid preservation cards (Flinders Technology Associates; FTA(r)) and has a
similar trap efficacy as standard light traps in our trials. METHODS: The trap
efficacy of the SMACK was assessed against Centers for Disease Control and
Prevention (CDC) miniature light traps (standard and ultraviolet) and the
Encephalitis Vector Survey (EVS) trap in a series of Latin square field trials
conducted in North Queensland, Australia. The ability of the SMACK to serve as a
sentinel arbovirus surveillance tool was assessed in comparison to Passive Box
Traps (PBT) during the 2014 wet season in the Cairns, Australia region and
individually in the remote Northern Peninsula Area (NPA) of Australia during the
2015 wet season. RESULTS: The SMACK caught comparable numbers of mosquitoes to
both CDC light traps (mean capture ratio 0.86: 1) and consistently outperformed
the EVS trap (mean capture ratio 2.28: 1) when CO2 was supplied by either a gas
cylinder (500 ml/min) or dry ice (1 kg). During the 2014 arbovirus survey, the
SMACK captured significantly (t 6 = 2.1, P = 0.04) more mosquitoes than the PBT,
and 2 and 1 FTA(r) cards were positive for Ross River virus and Barmah Forest
virus, respectively, while no arboviruses were detected from PBTs. Arbovirus
activity was detected at all three surveillance sites during the NPA survey in
2015 and ca. 27 % of FTA(r) cards tested positive for either Murray Valley
encephalitis virus (2 detections), West Nile virus (Kunjin subtype; 13
detections), or both viruses on two occasions. CONCLUSIONS: These results
demonstrate that the SMACK is a versatile, simple, and effective passive
arbovirus surveillance tool that may also be used as a traditional overnight
mosquito trap and has the potential to become a practical substitute for sentinel
animal programs.
PMID- 26444266
TI - [Funding for Health Care Innovation in Germany - New Chances for Optimized Care
for Severely Mentally Ill?].
PMID- 26444265
TI - Trends in upper gastrointestinal diagnosis over four decades in Lusaka, Zambia: a
retrospective analysis of endoscopic findings.
AB - BACKGROUND AND AIMS: There a shortage of robust information about profiles of
gastrointestinal disease in sub-Saharan Africa. The endoscopy unit of the
University Teaching Hospital in Lusaka has been running without interruption
since 1977 and this 38-year record is largely intact. We report an analysis of
endoscopic findings over this period. METHODS: Written endoscopy records from
29th September 1977 to 16th December 2014 were recovered, computerised, coded by
two experienced endoscopists and analysed. Temporal trends were analysed using
tables, graphs, and unconditional logistic regression, with age, sex of patient,
decade, and endoscopist as independent variables to adjust for inter-observer
variation. RESULTS: Sixteen thousand nine hundred fifty-three records were
identified and analysed. Diagnosis of gastric ulcer rose by 22 %, and that of
duodenal ulcer fell by 14 % per decade. Endoscopically diagnosed oesophageal
cancer increased by 32 % per decade, but gastric cancer rose only in patients
under 60 years of age (21 % per decade). Oesophageal varices were the commonest
finding in patients presenting with haematemesis, increasing by 14 % per decade
in that patient group. Two HIV-related diagnoses, oesophageal candidiasis and
Kaposi's sarcoma, rose from almost zero to very high levels in the 1990s but fell
substantially after 2005 when anti-retroviral therapy became widely available.
CONCLUSIONS: This useful dataset suggests that there are important trends in some
endoscopic findings over four decades. These trends are not explained by inter
observer variation. Reasons for the divergent trends in incidence of peptic
ulceration and apparent trends in diagnosis of upper gastrointestinal cancers
merit further exploration.
PMID- 26444267
TI - [Discharge on the Day After Admission Following Announcement of Suicide - Pro].
PMID- 26444268
TI - [Discharge on the Day After Admission Following Announcement of Suicide -
Contra].
PMID- 26444269
TI - [News releases from the Federal Directors' Conference].
PMID- 26444270
TI - Inhibition of oleandrin on the proliferation show and invasion of osteosarcoma
cells in vitro by suppressing Wnt/beta-catenin signaling pathway.
AB - BACKGROUND: Osteosarcoma (OS) is a high-grade bone sarcoma with early metastasis
potential, and the clinical chemotherapy drugs that are currently used for its
treatment have some limitations. Recently, several studies have reported the
selective antitumor effect of oleandrin on various tumor cells. In this study, we
aimed to evaluate the effects and underlying mechanisms of oleandrin on OS cells.
METHODS: The effect of oleandrin on the proliferation, morphology, and apoptosis
of U2OS and SaOS-2 cells were analyzed in vitro. The activity of the Wnt/beta
catenin signaling pathway was determined using a dual luciferase assay. Semi
quantitative RT-PCR and western blot assays were performed to evaluate the mRNA
and total protein expression of the downstream target genes. Changes of beta
catenin in intracellular localization were also explored using a western blot
after separating the nucleus and cytoplasm proteins. The MMP-2 and MMP-9
enzymatic activities were determined using gelatin zymography. RESULTS: Oleandrin
significantly inhibited the proliferation and invasion of OS cells in vitro, and
induced their apoptosis. After treatment with oleandrin, the TOP/FOP flash ratio
in OS cells was noticeably decreased, which indicated that the Wnt/beta-catenin
signaling pathway was repressed. The expression of related Wnt target genes and
total beta-catenin was downregulated, and a reduced nuclear beta-catenin level by
oleandrin was observed as well. In addition, oleandrin suppressed the activities
of MMP-2 and MMP-9. CONCLUSIONS: Oleandrin, in vitro, exerted a strong antitumor
effect on human OS cells by suppressing the Wnt/beta-catenin signaling pathway,
which interfered with the proliferation and invasion of OS cells, as well as
induced cells apoptosis. Moreover, the expression and activities of MMP-2 and MMP
9 were downregulated by oleandrin, which contributed to the cells' lower
invasiveness.
PMID- 26444271
TI - Reduced cortical thickness in patients with acute-on-chronic liver failure due to
non-alcoholic etiology.
AB - BACKGROUND: Acute-on-chronic liver failure (ACLF) is a form of liver disease with
high short-term mortality. ACLF offers considerable potential to affect the
cortical areas by significant tissue injury due to loss of neurons and other
supporting cells. We measured changes in cortical thickness and metabolites
profile in ACLF patients following treatment, and compared it with those of age
matched healthy volunteers. METHODS: For the cortical thickness analysis we
performed whole brain high resolution T1-weighted magnetic resonance imaging
(MRI) on 15 ACLF and 10 healthy volunteers at 3T clinical MR scanner. Proton MR
Spectroscopy ((1)H MRS) was also performed to measure level of altered
metabolites. Out of 15 ACLF patients 10 survived and underwent follow-up study
after clinical recovery at 3 weeks. FreeSurfer program was used to quantify
cortical thickness and LC- Model software was used to quantify absolute
metabolites concentrations. Neuropsychological (NP) test was performed to assess
the cognitive performance in follow-up ACLF patients compared to controls.
RESULTS: Significantly reduced cortical thicknesses in multiple brain sites, and
significantly decreased N-acetyl aspartate (NAA), myo-inositol (mI) and
significantly increased glutamate/glutamine (glx) metabolites were observed in
ACLF compared to those of controls at baseline study. Follow-up patients showed
significant recovery in cortical thickness and Glx level, while NAA and mI were
partially recovered compared to baseline study. When compared to controls, follow
up patients still showed reduced cortical thickness and altered metabolites
level. Follow-up patients had abnormal neuropsychological (NP) scores compared to
controls. CONCLUSIONS: Neuronal loss as suggested by the reduced NAA, decreased
cellular density due to increased cerebral hyperammonemia as supported by the
increased glx level, and increased proinflammatory cytokines and free radicals
may account for the reduced cortical thickness in ACLF patients. Presence of
reduced cortical thickness, altered metabolites and abnormal NP test scores in
post recovery subjects as compared to those of controls is associated with
incomplete clinical recovery. The current imaging protocol can be easily
implemented in clinical settings to evaluate and monitor brain tissue changes in
patients with ACLF during the course of treatment.
PMID- 26444272
TI - Availability of emergency neonatal care in eight districts of Karnataka state,
southern India: a cross-sectional study.
AB - BACKGROUND: Emergency Neonatal Care (EmNC) is an important service for the health
and survival of newborns. The objective of our study was to assess the
availability of emergency neonatal care services in the north-eastern region of
Karnataka state in India. METHODS: We undertook a cross-sectional epidemiologic
study in the year 2010. We assessed the provision of eight life-saving 'signal
functions' (Comprehensive EmNC) or at least five 'signal functions' (Basic EmNC)
by self-reporting through a structured questionnaire, coupled with verification
by direct observation for presence of drugs and equipment in the prior three
months. The assessment was undertaken in 443 government and 422 private
healthcare facilities of eight districts of Karnataka. RESULTS: There was an
average of 3.6 EmNC facilities available per 500,000 population for the entire
region. Only three out of eight districts and 10 of 42 sub-districts in the
region had the recommended [greater than or equal to 5] EmNC facilities per
500,000. Further, over 95 % of CEmNC facilities and 88 % of BEmNC facilities were
within the private sector. About 80 % of government hospitals at district and sub
district levels did not have EmNC capability. CONCLUSIONS: This study
demonstrates the feasibility of using a simple assessment tool to measure health
facility availability of life-saving services for newborn care. EmNC availability
was seen to be suboptimal at the regional, district and sub-district levels
within the northern part of Karnataka state. There is a need to improve
availability of emergency newborn care in health facilities, with special
emphasis on equity at population level.
PMID- 26444273
TI - Battery electric vehicles - implications for the driver interface.
AB - The current study examines the human-machine interface of a battery electric
vehicle (BEV) from a user-perspective, focussing on the evaluation of BEV
specific displays, the relevance of provided information and challenges for
drivers due to the concept of electricity in a road vehicle. A sample of 40 users
drove a BEV for 6 months. Data were gathered at three points of data collection.
Participants perceived the BEV-specific displays as only moderately reliable and
helpful for estimating the displayed parameters. This was even less the case
after driving the BEV for 3 months. A taxonomy of user requirements was compiled
revealing the need for improved and additional information, especially regarding
energy consumption and efficiency. Drivers had difficulty understanding
electrical units and the energy consumption of the BEV. On the background of
general principles for display design, results provide implications how to
display relevant information and how to facilitate drivers' understanding of
energy consumption in BEVs. Practitioner Summary: Battery electric vehicle (BEV)
displays need to incorporate new information. A taxonomy of user requirements was
compiled revealing the need for improved and additional information in the BEV
interface. Furthermore, drivers had trouble understanding electrical units and
energy consumption; therefore, appropriate assistance is required. Design
principles which are specifically important in the BEV context are discussed.
PMID- 26444274
TI - The degree of local inflammatory response after colonic resection depends on the
surgical approach: an observational study in 61 patients.
AB - BACKGROUND: Clinical data indicate that laparoscopic surgery reduces
postoperative inflammatory response and benefits patient recovery. Little is
known about the mechanisms involved in reduced systemic and local inflammation
and the contribution of reduced trauma to the abdominal wall and the parietal
peritoneum. METHODS: Included were 61 patients, who underwent elective colorectal
resection without intraabdominal complications; 17 received a completely
laparoscopic, 13 a laparoscopically- assisted procedure and 31 open surgery.
Local inflammatory response was quantified by measurement of intraperitoneal
leukocytes and IL-6 levels during the first 4 days after surgery. RESULTS: There
was no statistical difference between the groups in systemic inflammatory
parameters and intraperitoneal leukocytes. Intraperitoneal interleukin-6 was
significantly lower in the laparoscopic group than in the laparoscopically
assisted and open group on postoperative day 1 (26.16 versus 43.25 versus 40.83
ng/ml; p = 0.001). No difference between the groups was recorded on POD 2-4.
Intraperitoneal interleukin-6 showed a correlation with duration of hospital stay
on POD 1 (0.233, p = 0.036), but not on POD 2-4. Patients who developed a
surgical wound infection showed higher levels of intraperitoneal interleukin-6 on
postoperative day 2-4 (POD 2: 42.56 versus 30.02 ng/ml, p = 0.03), POD 3: 36.52
versus 23.62 ng/ml, p = 0.06 and POD 4: 34.43 versus 19.99 ng/ml, p = 0.046).
Extraabdominal infections had no impact. CONCLUSION: The analysis shows an
attenuated intraperitoneal inflammatory response on POD 1 in completely
laparoscopically-operated patients, associated with a quicker recovery. This
effect cannot be observed in patients, who underwent a laparoscopically-assisted
or open procedure. Factors inflicting additional trauma to the abdominal wall and
parietal peritoneum promote the intraperitoneal inflammation process.
PMID- 26444275
TI - The transcatheter aortic valve implementation (TAVI)--a qualitative approach to
the implementation and diffusion of a minimally invasive surgical procedure.
AB - BACKGROUND: The transcatheter aortic valve implantation (TAVI), a minimally
invasive surgical procedure to treat patients with severe symptomatic aortic
stenosis, showed a rapid diffusion in Germany compared to the international
level. The aim of this study is to identify and analyze factors affecting the
implementation and diffusion of the procedure in hospitals using a qualitative
application of the diffusion of innovations theory. METHODS: We conducted problem
centered interviews with cardiologists and cardiac surgeons working in German
hospitals. The multi-level model "diffusion of innovations in health services
organizations" developed by Greenhalgh et al. was used to guide the research.
Data was analyzed using content and a thematic analysis. RESULTS: Among the ten
participants who were interviewed, we found both barriers and facilitators
related to the innovation itself, system readiness and antecedents, communication
and influence, and the outer context. Key issues were the collaboration between
cardiologists and cardiac surgeons, reimbursement policies, requirements needed
to conduct the procedure, and medical advantages of the method. CONCLUSIONS: The
findings show that there are multiple factors influencing the diffusion of TAVI
that go beyond the reimbursement and cost issues. The diffusion of innovations
model proved to be helpful in understanding the different aspects of the uptake
of the procedure. A central theme that affected the implementation of TAVI was
the collaboration and competition between involved medical departments:
cardiology and cardiac surgery. Against this background, it seems especially
important to moderate and coordinate the cooperation of the different medical
disciplines.
PMID- 26444276
TI - ?
PMID- 26444277
TI - ?
PMID- 26444278
TI - ?
PMID- 26444279
TI - Increased ratio of neutrophil elastase to alpha1-antitrypsin is closely
associated with liver inflammation in patients with nonalcoholic steatohepatitis.
AB - An imbalance between neutrophil elastase (NE) and its inhibitor alpha1
antitrypsin (A1 AT) is known to contribute to the development of obesity-related
inflammation. This study aimed to investigate the role of the NE-A1 AT system in
the histological progression of non-alcoholic fatty liver disease (NAFLD), and to
evaluate the ability of it to predict nonalcoholic steatohepatitis (NASH). A
total of 252 adults (NAFLD group, n = 202; healthy group, n = 50) were recruited.
Clinical biochemical characteristics, NE and A1 AT concentrations were measured
in all subjects. Among the NAFLD group, 86 patients had previously undergone
liver biopsy and information on histological characteristics was consequently
available. The area under the receiver operating characteristic curve (AUC) was
used to determine the predictive accuracy of the NE-A1 AT system for NASH. NAFLD
patients had an elevated serum NE concentration and a reduced A1 AT level with
consequent NE/A1 AT imbalance. NE increased in the early stage of steatosis,
preceding the decline in A1 AT, dating from the onset of NASH (NAS 3-4), and
subsequently NE/A1 AT increased in the presence of NASH. Nonetheless, this
increase began to resolve as the disease state progressed to advanced fibrosis.
A1 AT had a sensitivity (SEN) of 83.8% and a specificity (SP) of 83.3% with the
optimal cut-off of -1459.43, NE/A1 AT had a SEN of 88.8% and a SP of 83.3% with
cut-off of 0.363 to predict NASH. An increased NE: A1 AT ratio is closely
associated with liver Inflammation in patients with NASH and could serve as a
novel marker to predict NASH in humans.
PMID- 26444280
TI - Spatial Niche Segregation of Sympatric Stone Marten and Pine Marten--Avoidance of
Competition or Selection of Optimal Habitat?
AB - Coexistence of ecologically similar species relies on differences in one or more
dimensions of their ecological niches, such as space, time and resources in diel
and/or seasonal scales. However, niche differentiation may result from other
mechanisms such as avoidance of high predation pressure, different adaptations or
requirements of ecologically similar species. Stone marten (Martes foina) and
pine marten (Martes martes) occur sympatrically over a large area in Central
Europe and utilize similar habitats and food, therefore it is expected that their
coexistence requires differentiation in at least one of their niche dimensions or
the mechanisms through which these dimensions are used. To test this hypothesis,
we used differences in the species activity patterns and habitat selection,
estimated with a resource selection function (RSF), to predict the relative
probability of occurrence of the two species within a large forest complex in the
northern geographic range of the stone marten. Stone martens were significantly
heavier, have a longer body and a better body condition than pine martens. We
found weak evidence for temporal niche segregation between the species. Stone and
pine martens were both primarily nocturnal, but pine martens were active more
frequently during the day and significantly reduced the duration of activity
during autumn-winter. Stone and pine martens utilized different habitats and
almost completely separated their habitat niches. Stone marten strongly preferred
developed areas and avoided meadows and coniferous or deciduous forests. Pine
marten preferred deciduous forest and small patches covered by trees, and avoided
developed areas and meadows. We conclude that complete habitat segregation of the
two marten species facilitates sympatric coexistence in this area. However,
spatial niche segregation between these species was more likely due to
differences in adaptation to cold climate, avoidance of high predator pressure
and/or food preferences by both species than competitive interaction between
them.
PMID- 26444281
TI - Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in
Mice.
AB - Metastasis to the liver is a main factor in colorectal cancer mortality. Previous
studies suggest that chronic psychological stress is important in cancer
progression, but its effect on liver metastasis has not been investigated. To
address this, we established a liver metastasis model in BALB/c nude mice to
investigate the role of chronic stress in liver metastasis. Our data suggest that
chronic stress elevates catecholamine levels and promotes liver metastasis.
Chronic stress was also associated with increased tumor associated macrophages
infiltration into the primary tumor and increased the expression of metastatic
genes. Interestingly, beta-blocker treatment reversed the effects of chronic
stress on liver metastasis. Our results suggest the beta-adrenergic signaling
pathway is involved in regulating colorectal cancer progression and liver
metastasis. Additionally, we submit that adjunctive therapy with a beta-blocker
may complement existing colorectal cancer therapies.
PMID- 26444283
TI - Complete Mitochondrial Genomes of New Zealand's First Dogs.
AB - Dogs accompanied people in their migrations across the Pacific Ocean and
ultimately reached New Zealand, which is the southern-most point of their oceanic
distribution, around the beginning of the fourteenth century AD. Previous ancient
DNA analyses of mitochondrial control region sequences indicated the New Zealand
dog population included two lineages. We sequenced complete mitochondrial genomes
of fourteen dogs from the colonisation era archaeological site of Wairau Bar and
found five closely-related haplotypes. The limited number of mitochondrial
lineages present at Wairau Bar suggests that the founding population may have
comprised only a few dogs; or that the arriving dogs were closely related. For
populations such as that at Wairau Bar, which stemmed from relatively recent
migration events, control region sequences have insufficient power to address
questions about population structure and founding events. Sequencing mitogenomes
provided the opportunity to observe sufficient diversity to discriminate between
individuals that would otherwise be assigned the same haplotype and to clarify
their relationships with each other. Our results also support the proposition
that at least one dispersal of dogs into the Pacific was via a south-western
route through Indonesia.
PMID- 26444284
TI - Temporal Patterns in Seawater Quality from Dredging in Tropical Environments.
AB - Maintenance and capital dredging represents a potential risk to tropical
environments, especially in turbidity-sensitive environments such as coral reefs.
There is little detailed, published observational time-series data that
quantifies how dredging affects seawater quality conditions temporally and
spatially. This information is needed to test realistic exposure scenarios to
better understand the seawater-quality implications of dredging and ultimately to
better predict and manage impacts of future projects. Using data from three
recent major capital dredging programs in North Western Australia, the extent and
duration of natural (baseline) and dredging-related turbidity events are
described over periods ranging from hours to weeks. Very close to dredging i.e.
<500 m distance, a characteristic features of these particular case studies was
high temporal variability. Over several hours suspended sediment concentrations
(SSCs) can range from 100-500 mg L-1. Less turbid conditions (10-80 mg L-1) can
persist over several days but over longer periods (weeks to months) averages were
<10 mg L-1. During turbidity events all benthic light was sometimes extinguished,
even in the shallow reefal environment, however a much more common feature was
very low light 'caliginous' or daytime twilight periods. Compared to pre-dredging
conditions, dredging increased the intensity, duration and frequency of the
turbidity events by 10-, 5- and 3-fold respectively (at sites <500 m from
dredging). However, when averaged across the entire dredging period of 80-180
weeks, turbidity values only increased by 2-3 fold above pre-dredging levels.
Similarly, the upper percentile values (e.g., P99, P95) of seawater quality
parameters can be highly elevated over short periods, but converge to values only
marginally above baseline states over longer periods. Dredging in these studies
altered the overall probability density distribution, increasing the frequency of
extreme values. As such, attempts to understand the potential biological impacts
must consider impacts across telescoping-time frames and changes to extreme
conditions in addition to comparing central tendency (mean/median). An analysis
technique to capture the entire range of likely conditions over time-frames from
hours to weeks is described using a running means/percentile approach.
PMID- 26444282
TI - Interleukin-1 Antagonist Anakinra in Amyotrophic Lateral Sclerosis--A Pilot
Study.
AB - Preclinical studies show that blocking Interleukin-1 (IL-1) retards the
progression of Amyotrophic Lateral Sclerosis (ALS). We assessed the safety of
Anakinra (ANA), an IL-1 receptor antagonist, in ALS patients. In a single arm
pilot study we treated 17 ALS patients with ANA (100 mg) daily for one year. We
selected patients with dominant or exclusive lower motor neuron degeneration
(LMND) presentation, as peripheral nerves may be more accessible to the drug. Our
primary endpoint was safety and tolerability. Secondary endpoints included
measuring disease progression with the revised ALS functional rating scale
(ALSFRSr). We also quantified serum inflammatory markers. For comparison, we
generated a historical cohort of 47 patients that fit the criteria for
enrollment, disease characteristics and rate of progression of the study group.
Only mild adverse events occurred in ALS patients treated with ANA. Notably, we
observed lower levels of cytokines and the inflammatory marker fibrinogen during
the first 24 weeks of treatment. Despite of this, we could not detect a
significant reduction in disease progression during the same period in patients
treated with ANA compared to controls as measured by the ALSFRSr. In the second
part of the treatment period we observed an increase in serum inflammatory
markers. Sixteen out of the 17 patients (94%) developed antibodies against ANA.
This study showed that blocking IL-1 is safe in patients with ALS. Further trials
should test whether targeting IL-1 more efficiently can help treating this
devastating disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT01277315.
PMID- 26444285
TI - Long Noncoding RNA MEG3 Interacts with p53 Protein and Regulates Partial p53
Target Genes in Hepatoma Cells.
AB - Maternally Expressed Gene 3 (MEG3) encodes a lncRNA which is suggested to
function as a tumor suppressor. Previous studies suggested that MEG3 functioned
through activation of p53, however, the functional properties of MEG3 remain
obscure and their relevance to human diseases is under continuous investigation.
Here, we try to illuminate the relationship of MEG3 and p53, and the consequence
in hepatoma cells. We find that transfection of expression construct of MEG3
enhances stability and transcriptional activity of p53. Deletion analysis of MEG3
confirms that full length and intact structure of MEG3 are critical for it to
activate p53-mediated transactivation. Interestingly, our results demonstrate for
the first time that MEG3 can interact with p53 DNA binding domain and various p53
target genes are deregulated after overexpression of MEG3 in hepatoma cells.
Furthermore, results of qRT-PCR have shown that MEG3 RNA is lost or reduced in
the majority of HCC samples compared with adjacent non-tumorous samples. Ectopic
expression of MEG3 in hepatoma cells significantly inhibits proliferation and
induces apoptosis. In conclusion, our data demonstrates that MEG3 functions as a
tumor suppressor in hepatoma cells through interacting with p53 protein to
activate p53-mediated transcriptional activity and influence the expression of
partial p53 target genes.
PMID- 26444286
TI - Kefir Grains Change Fatty Acid Profile of Milk during Fermentation and Storage.
AB - Several studies have reported that lactic acid bacteria may increase the
production of free fatty acids by lipolysis of milk fat, though no studies have
been found in the literature showing the effect of kefir grains on the
composition of fatty acids in milk. In this study the influence of kefir grains
from different origins [Rio de Janeiro (AR), Vicosa (AV) e Lavras (AD)],
different time of storage, and different fat content on the fatty acid content of
cow milk after fermentation was investigated. Fatty acid composition was
determined by gas chromatography. Values were considered significantly different
when p<0.05. The highest palmitic acid content, which is antimutagenic compost,
was seen in AV grain (36.6g/100g fatty acids), which may have contributed to
increasing the antimutagenic potential in fermented milk. Higher monounsaturated
fatty acid (25.8 g/100g fatty acids) and lower saturated fatty acid (72.7 g/100g
fatty acids) contents were observed in AV, when compared to other grains, due to
higher Delta9-desaturase activity (0.31) that improves the nutritional quality of
lipids. Higher oleic acid (25.0 g/100g fatty acids) and monounsaturated fatty
acid (28.2g/100g fatty acids) and lower saturated fatty acid (67.2g/100g fatty
acids) contents were found in stored kefir relatively to fermented kefir leading
to possible increase of antimutagenic and anticarcinogenic potential and
improvement of nutritional quality of lipids in storage milk. Only high-lipidic
matrix displayed increase polyunsaturated fatty acids after fermentation. These
findings open up new areas of study related to optimizing desaturase activity
during fermentation in order to obtaining a fermented product with higher
nutritional lipid quality.
PMID- 26444287
TI - Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal
Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate
Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan.
AB - BACKGROUND: Currently in Japan, both 23-valent pneumococcal polysaccharide
vaccine (PPSV-23) and 13-valent pneumococcal conjugate vaccine (PCV-13) are
available for the elderly for the prevention of S. pneumoniae-related diseases.
PPSV-23 was approved in 1988, while the extended use of PCV-13 was approved for
adults aged 65 and older in June 2014. Despite these two vaccines being
available, the recently launched national immunisation programme for the elderly
only subsidised PPSV-23. The framework of the current immunisation programme
lasts for five years. The elderly population eligible for the subsidised PPSV-23
shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and >= 100. While
from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95
and 100 will receive the same subsidised shot. METHODS: We performed economic
evaluations to (1) evaluate the efficiency of alternative strategies of PPSV-23
single-dose immunisation programme, and (2) investigate the efficiency of PCV-13
inclusion in the list for single-dose pneumococcal vaccine immunisation
programme. Three alternative strategies were created in this study, namely: (1)
current PPSV-23 strategy, (2) 65 to 80 (as "65-80 PPSV-23 strategy"), and (3) 65
and older (as ">= 65 PPSV-23 strategy"). We constructed a Markov model depicting
the S. pneumoniae-related disease course pathways. The transition probabilities,
utility weights to estimate quality adjusted life year (QALY) and disease
treatment costs were either calculated or cited from literature. Cost of per shot
of vaccine was Y 8,116 (US$74; US$1 = Y 110) for PPSV-23 and Y 10,776 (US$98) for
PCV-13. The model runs for 15 years with one year cycle after immunisation.
Discounting was at 3%. RESULTS: Compared to current PPSV-23 strategy, 65-80 PPSV
23 strategy cost less but gained less, while the incremental cost-effectiveness
ratios (ICERs) of >= 65 PPSV-23 strategy was Y 5,025,000 (US$45,682) per QALY
gained. PCV-13 inclusion into the list for single-dose subsidy has an ICER of Y
377,000 (US$3,427) per QALY gained regardless of the PCV-13 diffusion level.
These ICERs were found to be cost-effective since they are lower than the
suggested criterion by WHO of three times GDP (Y 11,000,000 or US$113,636 per
QALY gained), which is the benchmark used in judging the cost-effectiveness of an
immunisation programmne. CONCLUSIONS: The results suggest that switching current
PPSV-23 strategy to >= 65 PPSV-23 strategy or including PCV-13 into the list for
single-dose subsidy to the elderly in Japan has value for money.
PMID- 26444288
TI - Multiplex Assay for Protein Profiling and Potency Measurement of German Cockroach
Allergen Extracts.
AB - BACKGROUND: German cockroach (GCr) allergens induce IgE responses and may cause
asthma. Commercial GCr allergen extracts are variable and existing assays may not
be appropriate for determining extract composition and potency. OBJECTIVE: Our
aim was to develop a multiplex antibody/bead-based assay for assessment of GCr
allergen extracts. METHODS: Single chain fragment variable (scFv) antibodies
against GCr were obtained by screening libraries derived from naive human
lymphocytes and hyperimmunized chicken splenocytes and bone marrow. Selected
clones were sequenced and characterized by immunoblotting. Eighteen scFv
antibodies (17 chicken, 1 human) coupled to polystyrene beads were used in this
suspension assay; binding of targeted GCr allergens to antibody-coated beads was
detected using rabbit antisera against GCr, and against specific allergens rBla g
1, rBla g 2, and rBla g 4. The assay was tested for specificity, accuracy, and
precision. Extracts were also compared by IgE competition ELISA. RESULTS: Chicken
scFv's generated eight different binding patterns to GCr proteins from 14 to 150
kDa molecular weight. Human scFv's recognized a 100 kDa GCr protein. The
multiplex assay was found to be specific and reproducible with intra-assay
coefficient of variation (CV) of 2.64% and inter-assay CV of 10.0%. Overall
potencies of various GCr extracts were calculated using mean logEC50s for eight
selected scFvs. Overall potency measures were also analyzed by assessing the
contributions to potency of each target. CONCLUSIONS: An scFv antibody-based
multiplex assay has been developed capable of simultaneously measuring different
proteins in a complex mixture, and to determine the potencies and compositions of
allergen extracts.
PMID- 26444290
TI - Intravitreal Injection of a Rho-Kinase Inhibitor (Fasudil) for Recent-Onset
Nonarteritic Anterior Ischemic Optic Neuropathy.
AB - This study evaluated the effects of intravitreal injection of fasudil (IVF), a
Rho-kinase inhibitor, in cases of recent-onset nonarteritic anterior ischemic
optic neuropathy (NAION). In this interventional case series, 13 eyes of 13
patients diagnosed with NAION within 14 days of onset were included. The affected
eyes received a 0.025 mg/0.05 mL IVF. Functional and structural outcomes were
assessed 1 and 3 months following treatment. Best corrected visual acuity (BCVA)
was the main outcome measured, with mean deviation (MD) index of the VF test and
peripapillary retinal nerve fiber layer thickness as secondary measures. There
was a statistically significant improvement in the patients' BCVA 1 and 3 months
following IVF; BCVA improved from 1.69 +/- 0.55 logMAR at baseline to 0.98 +/-
0.47 and 0.93 +/- 0.51 logMAR at 1 and 3 months, respectively (P = .004). The
change in BCVA was not significant between month 1 and month 3 (P = .22).
Peripapillary retinal nerve fiber layer thickness decreased from 173.5 +/- 29.28
um in the baseline evaluation to 85.8 +/- 8.8 um at 1 month, and 62.9 +/- 5.97 um
at 3 months (P = .003). MD values changed from 24.60 +/- 3.80 to 21.0 +/- 6.10
and 20.5 +/- 6.50 at 1 and 3 months, respectively (P = .007 and .005,
respectively). This pilot study suggests that IVF may be an effective treatment
for patients with recent-onset NAION. Larger studies are required to establish
the therapeutic role of fasudil for NAION.
PMID- 26444289
TI - Defense of Elevated Body Weight Setpoint in Diet-Induced Obese Rats on Low Energy
Diet Is Mediated by Loss of Melanocortin Sensitivity in the Paraventricular
Hypothalamic Nucleus.
AB - Some animals and humans fed a high-energy diet (HED) are diet-resistant (DR),
remaining as lean as individuals who were naive to HED. Other individuals become
obese during HED exposure and subsequently defend the obese weight (Diet-Induced
Obesity- Defenders, DIO-D) even when subsequently maintained on a low-energy
diet. We hypothesized that the body weight setpoint of the DIO-D phenotype
resides in the hypothalamic paraventricular nucleus (PVN), where anorexigenic
melanocortins, including melanotan II (MTII), increase presynaptic GABA release,
and the orexigenic neuropeptide Y (NPY) inhibits it. After prolonged return to
low-energy diet, GABA inputs to PVN neurons from DIO-D rats exhibited highly
attenuated responses to MTII compared with those from DR and HED-naive rats. In
DIO-D rats, melanocortin-4 receptor expression was significantly reduced in
dorsomedial hypothalamus, a major source of GABA input to PVN. Unlike
melanocortin responses, NPY actions in PVN of DIO-D rats were unchanged, but were
reduced in neurons of the ventromedial hypothalamic nucleus; in PVN of DR rats,
NPY responses were paradoxically increased. MTII-sensitivity was restored in DIO
D rats by several weeks' refeeding with HED. The loss of melanocortin sensitivity
restricted to PVN of DIO-D animals, and its restoration upon prolonged refeeding
with HED suggest that their melanocortin systems retain the ability to up- and
downregulate around their elevated body weight setpoint in response to longer
term changes in dietary energy density. These properties are consistent with a
mechanism of body weight setpoint.
PMID- 26444291
TI - Do Interventions that Promote Awareness of Rights Increase Use of Maternity Care
Services? A Systematic Review.
AB - Twenty years after the rights of women to go through pregnancy and childbirth
safely were recognized by governments, we assessed the effects of interventions
that promote awareness of these rights to increase use of maternity care
services. Using inclusion and exclusion criteria defined in a peer-reviewed
protocol, we searched published and grey literature from one database of studies
on maternal health, two search engines, an internet search and contact with
experts. From the 707 unique documents found, 219 made reference to rights, with
22 detailing interventions promoting awareness of rights for maternal and newborn
health. Only four of these evaluated effects on health outcomes. While all four
interventions promoted awareness of rights, they did so in different ways.
Interventions included highly-scripted dissemination meetings with educational
materials and other visual aids, participatory approaches that combined raising
awareness of rights with improving accountability of services, and broader multi
stakeholder efforts to improve maternal health. Study quality ranged from weak to
strong. Measured health outcomes included increased antenatal care and facility
birth. Improvements in human rights outcomes such as availability, acceptability,
accessibility, quality of care, as well as the capacity of rights holders and
duty bearers were also reported to varying extents. Very little information on
costs and almost no information on harms or risks were described. Despite
searching multiple sources of information, while some studies did report on
activities to raise awareness of rights, few detailed how they did so and very
few measured effects on health outcomes. Promoting awareness of rights is one
element of increasing demand for and use of quality maternity care services for
women during pregnancy, birth and after birth. To date efforts have not been well
documented in the literature and the program theories, processes and costs, let
alone health effects have not been well evaluated.
PMID- 26444292
TI - An Organocatalytic Regiospecific Synthesis of 1,5-Disubstituted 4-Thio-1,2,3
triazoles and 1,5-Disubstituted 1,2,3-Triazoles.
AB - Organocatalytic azide-ketone [3+2] cycloaddition (OrgAKC) of a variety of 1-aryl
2-(arylthio)ethanones and 1-alkyl-2-(alkylthio)ethanones with different aryl or
alkyl azides is reported in dimethyl sulfoxide or solvent-free under ambient
conditions to furnish 1,5-disubstituted 4-thio-1,2,3-triazoles in a regiospecific
manner, which are further converted into useful 1,5-disubstituted 1,2,3-triazoles
by treatment with Raney Ni at 25 degrees C for 1-3 h. Notable features of the
OrgAKC reaction include high rate and selectivity, solvent-free conditions,
easily available substrates and catalysts, a wide range of synthetic and
medicinal applications, and excellent yields generating a vast library of
triazoles.
PMID- 26444293
TI - Determining the Optimum Power Load in Jump Squat Using the Mean Propulsive
Velocity.
AB - The jump squat is one of the exercises most frequently used to improve lower body
power production, which influences sports performance. However, the traditional
determination of the specific workload at which power production is maximized
(i.e., optimum power load) is time-consuming and requires one-repetition maximum
tests. Therefore, the aim of this study was to verify whether elite athletes from
different sports would produce maximum mean propulsive power values at a narrow
range of mean propulsive velocities, resulting in similar jump heights. One
hundred and nine elite athletes from several individual/team sport disciplines
underwent repetitions at maximal velocity with progressive loads, starting at 40%
of their body mass with increments of 10% to determine the individual optimum
power zone. Results indicated that regardless of sport discipline, the athletes'
optimum mean propulsive power was achieved at a mean propulsive velocity close to
1.0 m.s(-1) (1.01 +/- 0.07 m.s(-1)) and at a jump height close to 20 cm (20.47 +/
1.42 cm). Data were narrowly scattered around these values. Therefore, jump
squat optimum power load can be determined simply by means of mean propulsive
velocity or jump height determination in training/testing settings, allowing it
to be implemented quickly in strength/power training.
PMID- 26444294
TI - A new rescue regimen with plasma exchange and rituximab in high-risk membranous
glomerulonephritis.
AB - BACKGROUND: Even though current treatment guidelines for idiopathic membranous
glomerulonephritis (iMGN) exist, many questions regarding an optimal therapy
remain unanswered. Complete remission cannot be achieved in all patients;
relapses occur, in some cases frequently, and side effects from the
immunosuppressive therapy are common. Therapeutic options in high-risk patients
not responding to standard immunosuppressive therapies are limited. Recent
research reveals that the human M-type phospholipase A2 receptor (PLA2 R) is a
causative factor in iMGN that parallels clinical disease activity. However, in
some patients, this correlation is not evident and additional undetermined
factors seem to play a role. DESIGN: We evaluated a new rescue protocol including
plasma exchanges (PE) against albumin, intravenous immunoglobulins (IVIGs) and
rituximab for 10 patients with a biopsy-proven diagnosis of iMGN who were therapy
resistant to all conventional regimens and had a urinary protein to creatinine
ratio of more than 10 000 mg/g Crea. We compared this protocol with standard
immunosuppressive protocols including monthly alternating prednisolone plus
cyclophosphamide (18 patients), cyclosporine plus prednisolone (23 patients) and
rituximab alone (eight patients) in a retrospective design. RESULTS: Our rescue
regimen with PE, IVIGs and rituximab achieved partial remission in 90% of
patients who had been otherwise refractory to therapy. The mean time to partial
remission was 2.1 months. Furthermore, two anti-PLA2 R-antibody negative patients
were also treated with this rescue regimen, achieving partial remission after 1
and 4 months. CONCLUSION: A combination of PE, IVIGs and rituximab is a treatment
option to consider for high-risk patients with iMGN who are refractory to
conventional therapy.
PMID- 26444295
TI - Callus Formation and Mineralization after Fracture with Different Fixation
Techniques: Minimally Invasive Plate Osteosynthesis versus Open Reduction
Internal Fixation.
AB - Minimally invasive plate osteosynthesis(MIPO) has been considered as an
alternative for fracture treatment. Previous study has demonstrated that MIPO
technique has the advantage of less soft tissue injury compared with open
reduction internal fixation (ORIF). However, the comparison of callus formation
and mineralization between two plate osteosynthesis methods remains unknown. In
this experiment, ulna fracture model was established in 42 beagle dogs. The
fractures underwent reduction and internal fixation with MIPO or ORIF. Sequential
fluorescent labeling and radiographs were applied to determine new callus
formation and mineralization in two groups after operation. At 4, 8 and 12 weeks
postoperatively, the animals were selected to be sacrificed and the ulna
specimens were analyzed by Micro-CT. The sections were also treated with Masson
staining for histological evaluation. More callus formation was observed in MIPO
group in early stage of fracture healing. The fracture union rate has no
significant difference between two groups. The results indicate that excessive
soft tissue stripping may impact early callus formation. As MIPO technique can
effectively reduce soft tissue injury with little incision, it is considered to
be a promising alternative for fracture fixation.
PMID- 26444296
TI - Novel process and catalytic materials for converting CO2 and H2 containing
mixtures to liquid fuels and chemicals.
AB - Carbon dioxide and water are renewable and the most abundant feedstocks for the
production of chemicals and fungible fuels. However, the current technologies for
production of hydrogen from water are not competitive. Therefore, reacting carbon
dioxide with hydrogen is not economically viable in the near future. Other
alternatives include natural gas, biogas or biomass for the production of carbon
dioxide, hydrogen and carbon monoxide mixtures that react to yield chemicals and
fungible fuels. The latter process requires a high performance catalyst that
enhances the reverse water-gas-shift (RWGS) reaction and Fischer-Tropsch
synthesis (FTS) to higher hydrocarbons combined with an optimal reactor system.
Important aspects of a novel catalyst, based on a Fe spinel and three-reactor
system developed for this purpose published in our recent paper and patent, were
investigated in this study. Potassium was found to be a key promoter that
improves the reaction rates of the RWGS and FTS and increases the selectivity of
higher hydrocarbons while producing mostly olefins. It changed the texture of the
catalyst, stabilized the Fe-Al-O spinel, thus preventing decomposition into Fe3O4
and Al2O3. Potassium also increased the content of Fe5C2 while shifting Fe in the
oxide and carbide phases to a more reduced state. In addition, it increased the
relative exposure of carbide iron on the catalysts surface, the CO2 adsorption
and the adsorption strength. A detailed kinetic model of the RWGS, FTS and
methanation reactions was developed for the Fe spinel catalyst based on extensive
experimental data measured over a range of operating conditions. Significant
oligomerization activity of the catalyst was found. Testing the pelletized
catalyst with CO2, CO and H2 mixtures over a range of operating conditions
demonstrated its high productivity to higher hydrocarbons. The composition of the
liquid (C5+) was found to be a function of the potassium content and the
composition of the feedstock.
PMID- 26444297
TI - Flexible behavioral capture-recapture modeling.
AB - We develop alternative strategies for building and fitting parametric capture
recapture models for closed populations which can be used to address a better
understanding of behavioral patterns. In the perspective of transition models, we
first rely on a conditional probability parameterization. A large subset of
standard capture-recapture models can be regarded as a suitable partitioning in
equivalence classes of the full set of conditional probability parameters. We
exploit a regression approach combined with the use of new suitable summaries of
the conditioning binary partial capture histories as a device for enlarging the
scope of behavioral models and also exploring the range of all possible
partitions. We show how one can easily find unconditional MLE of such models
within a generalized linear model framework. We illustrate the potential of our
approach with the analysis of some known datasets and a simulation study.
PMID- 26444300
TI - A method for estimating spatial resolution of real image in the Fourier domain.
AB - Spatial resolution is a fundamental parameter in structural sciences. In
crystallography, the resolution is determined from the detection limit of high
angle diffraction in reciprocal space. In electron microscopy, correlation in the
Fourier domain is used for estimating the resolution. In this paper, we report a
method for estimating the spatial resolution of real images from a logarithmic
intensity plot in the Fourier domain. The logarithmic intensity plots of test
images indicated that the full width at half maximum of a Gaussian point spread
function can be estimated from the images. The spatial resolution of imaging X
ray microtomography using Fresnel zone-plate optics was also estimated with this
method. A cross section of a test object visualized with the imaging
microtomography indicated that square-wave patterns up to 120-nm pitch were
resolved. The logarithmic intensity plot was calculated from a tomographic cross
section of brain tissue. The full width at half maximum of the point spread
function estimated from the plot coincided with the resolution determined from
the test object. These results indicated that the logarithmic intensity plot in
the Fourier domain provides an alternative measure of the spatial resolution
without explicitly defining a noise criterion.
PMID- 26444299
TI - Purification and characterization of a highly active chromate reductase from
endophytic Bacillus sp. DGV19 of Albizzia lebbeck (L.) Benth. actively involved
in phytoremediation of tannery effluent-contaminated sites.
AB - Phytoremediation using timber-yielding tree species is considered to be the most
efficient method for chromium/tannery effluent-contaminated sites. In this study,
we have chosen Albizzia lebbeck, a chromium hyperaccumulator plant, and studied
one of its chromium detoxification processes operated by its endophytic bacterial
assemblage. Out of the four different groups of endophytic bacteria comprising
Pseudomonas, Rhizobium, Bacillus, and Salinicoccus identified from A. lebbeck
employed in phytoremediation of tannery effluent-contaminated soil, Bacillus
predominated with three species, which exhibited not only remarkable chromium
accumulation ability but also high chromium reductase activity. A chromate
reductase was purified to homogeneity from the most efficient chromium
accumulator, Bacillus sp. DGV 019, and the purified 34.2-kD enzyme was observed
to be stable at temperatures from 20 degrees C to 60 degrees C. The enzyme was
active over a wide range of pH values (4.0-9.0). Furthermore, the enzyme activity
was enhanced with the electron donors NADH, followed by NADPH, not affected by
glutathione and ascorbic acid. Cu(2+) enhanced the activity of the purified
enzyme but was inhibited by Zn(2+) and etheylenediamine tetraacetic acid (EDTA).
In conclusion, due to its versatile adaptability the chromate reductase can be
used for chromium remediation.
PMID- 26444301
TI - Impact of pH and Total Soluble Solids on Enzyme Inactivation Kinetics during High
Pressure Processing of Mango (Mangifera indica) Pulp.
AB - This study was undertaken with an aim to enhance the enzyme inactivation during
high pressure processing (HPP) with pH and total soluble solids (TSS) as
additional hurdles. Impact of mango pulp pH (3.5, 4.0, 4.5) and TSS (15, 20, 25
degrees Brix) variations on the inactivation of pectin methylesterase (PME),
polyphenol oxidase (PPO), and peroxidase (POD) enzymes were studied during HPP at
400 to 600 MPa pressure (P), 40 to 70 degrees C temperature (T), and 6- to 20
min pressure-hold time (t). The enzyme inactivation (%) was modeled using second
order polynomial equations with a good fit that revealed that all the enzymes
were significantly affected by HPP. Response surface and contour models predicted
the kinetic behavior of mango pulp enzymes adequately as indicated by the small
error between predicted and experimental data. The predicted kinetics indicated
that for a fixed P and T, higher pulse pressure effect and increased isobaric
inactivation rates were possible at lower levels of pH and TSS. In contrast, at a
fixed pH or TSS level, an increase in P or T led to enhanced inactivation rates,
irrespective of the type of enzyme. PPO and POD were found to have similar
barosensitivity, whereas PME was found to be most resistant to HPP. Furthermore,
simultaneous variation in pH and TSS levels of mango pulp resulted in higher
enzyme inactivation at lower pH and TSS during HPP, where the effect of pH was
found to be predominant than TSS within the experimental domain. PRACTICAL
APPLICATION: Exploration of additional hurdles such as pH, TSS, and temperature
for enzyme inactivation during high pressure processing of fruits is useful from
industrial point of view, as these parameters play key role in preservation
process design.
PMID- 26444302
TI - Effect of Airway Pressure Release Ventilation on Dynamic Alveolar Heterogeneity.
AB - IMPORTANCE: Ventilator-induced lung injury may arise from heterogeneous lung
microanatomy, whereby some alveoli remain collapsed throughout the breath cycle
while their more compliant or surfactant-replete neighbors become overdistended,
and this is called dynamic alveolar heterogeneity. OBJECTIVE: To determine how
dynamic alveolar heterogeneity is influenced by 2 modes of mechanical
ventilation: low tidal-volume ventilation (LTVV) and airway pressure release
ventilation (APRV), using in vivo microscopy to directly measure alveolar size
distributions. DESIGN, SETTING, AND PARTICIPANTS: In a randomized, nonblinded
laboratory animal study conducted between January 2013 and December 2014, 14 rats
(450-500 g in size) were randomized to a control group with uninjured lungs (n =
4) and 2 experimental groups with surfactant deactivation induced by polysorbate
lavage: the LTVV group (n = 5) and the APRV group (n = 5). For all groups, a
thoracotomy and in vivo microscopy were performed. Following lung injury induced
by polysorbate lavage, the LTVV group was ventilated with a tidal volume of 6
mL/kg and progressively higher positive end-expiratory pressure (PEEP) (5, 10,
16, 20, and 24 cm H2O). Following lung injury induced by polysorbate lavage, the
APRV group was ventilated with a progressively shorter time at low pressure,
which increased the ratio of the end-expiratory flow rate (EEFR) to the peak
expiratory flow rate (PEFR; from 10% to 25% to 50% to 75%). MAIN OUTCOMES AND
MEASURES: Alveolar areas were quantified (using PEEP and EEFR to PEFR ratio) to
determine dynamic heterogeneity. RESULTS: Following lung injury induced by
polysorbate lavage, a higher PEEP (20-24 cm H2O) with LTVV resulted in alveolar
occupancy (reported as percentage of total frame area) at inspiration (39.9%
42.2%) and expiration (35.9%-38.7%) similar to that in the control group
(inspiration 53.3%; expiration 50.3%; P > .01). Likewise, APRV with an increased
EEFR to PEFR ratio (50%-75%) resulted in alveolar occupancy at inspiration (46.7%
47.9%) and expiration (40.2%-46.6%) similar to that in the control group (P >
.01). At inspiration, the distribution of the alveolar area of the control group
was similar to that of the APRV group (P > .01) (but not to that of the LTVV
group [P < .01]). A lower PEEP (5-10 cm H2O) and a decreased EEFR to PEFR ratio
(<=50%) demonstrated dynamic heterogeneity between inspiration and expiration (P
< .01 for both) with a greater percentage of large alveoli at expiration. Dynamic
alveolar homogeneity between inspiration and expiration occurred with higher PEEP
(16-24 cm H2O) (P > .01) and an increased EEFR to PEFR ratio (75%) (P > .01).
CONCLUSIONS AND RELEVANCE: Increasing PEEP during LTVV increased alveolar
recruitment and dynamic homogeneity but had a significantly different alveolar
size distribution compared with the control group. By comparison, reducing the
time at low pressure (EEFR to PEFR ratio of 75%) in the APRV group provided
dynamic homogeneity and a closer approximation of the dynamics observed in the
control group.
PMID- 26444303
TI - Nitrogen content and morphology dependent field emission properties of nitrogen
doped SiC nanowires and density functional calculations.
AB - Nitrogen-doped SiC nanowires (N-doped SiC NWs) with a nitrogen content from 0.975
wt% to 2.265 wt% have been synthesized via a one-step chemical vapor reaction
(CVR), where melamine served as both the carbon and nitrogen source.
Interestingly, the morphology of the products changed from slightly curled to
very curled with crowding together with the increase of N dopants, which was
interpreted reasonably by the proposed N-doping growth model of SiC NWs. In
addition, according to the electronic structure calculation results, the band gap
is narrowed progressively with the increase of N content, which greatly enhances
the field emission (FE) properties. However, the experimental results of the FE
measurements substantiate that only when the N content takes an optimal value can
the N-doped SiC NWs act as candidates for field emitters with very low turn-on
fields (E(to)) of 1.5 V MUm(-1) and threshold fields (E(thr)) of 4 V MUm(-1). On
the basis of the aforementioned phenomenon, a universal cooperativity mechanism
was put forward to explain the effect of the N content and morphology on the FE
properties of the N-doped SiC NWs.
PMID- 26444310
TI - Driven by Ambitions: The Nurse Practitioner's Role Transition in Dutch Hospital
Care.
AB - INTRODUCTION: Insight into nurse practitioners' (NPs') role transition can help
NP students and new graduates in taking on new responsibilities in a changing and
demanding healthcare context. The aim of the research was to explore the role
transition from nurse to NP using the components of Meleis's Framework of
Transitions. METHOD: A qualitative descriptive design was used. Individual
interviews (n = 9) and two focus group discussions (n = 12) were held with NPs.
Data were analyzed with the directed content analysis method. FINDINGS: The
Framework component transitions' nature was characterized by changes in the
healthcare system, combined with professional and educational role changes.
Transition conditions showed that the respondents felt distressed after they
became accountable for a patient's care and well-being. Although the respondents
were authorized to do medical procedures, they initially lacked nursing role
models and NP protocols. Process indicators showed ongoing transition; the
respondents were still developing clinical competencies and confidence in patient
care while relying on earlier acquired nursing competencies. Outcome indicators
showed that the respondents found themselves successful in the medical extension
of two different nursing roles: continuity of medical care for hospitalized
patients in acute and intensive care settings, and being responsible for
continuity of care for chronic patients in outpatient clinics. CONCLUSIONS: Role
transition was characterized by coping with feelings of distress at the cost of
time and effort. The respondents' strategies to adapt to new expectations,
combined with organizational support, determined the outcomes as well as the
start of new transitions. CLINICAL RELEVANCE: NPs' role transition in hospital
care implies a dynamic ongoing process that needs to be supported, with the
ultimate goal to improve patient outcomes.
PMID- 26444311
TI - Association of general and abdominal obesity with age, endocrine and metabolic
factors in Asian men.
AB - OBJECTIVE: This study made use of the percent abdominal fat to define abdominal
obesity (AbO) and examined the differential associations of general obesity (GOb)
and AbO with age, metabolic and endocrine factors. METHODS: Metabolic, endocrine
and anthropometric factors and body composition were measured in 481 Asian men.
RESULTS: A DEXA-derived >=25% abdominal fat (PAbdF) was used to define men with
AbO. Age was directly associated with PAbdF and percent total body fat (PBF).
Exercise intensity was negatively associated with PBF. Both PBF and PAbdF were
associated with HDL and LDL, but have opposite correlation with triglyceride.
Furthermore, both PBF and PAbdF were associated with the number of metabolic
syndrome (MetS) risk factors. Men with GOb had lower levels of percent lean mass
(PLM), testosterone and bioavailable testosterone, and higher insulin and glucose
levels. Men with AbO had lower arm and leg fat, higher insulin levels and
triglycerides. CONCLUSIONS: Men with GOb and AbO had different pattern of body
composition. Age may be a contributory factor in AbO and a sedentary lifestyle
may contribute to GOb. Both GOb and AbO are associated with an increased risk of
MetS, with GOb more predispose to risk of diabetes, while AbO more at risk for
cardiovascular diseases.
PMID- 26444312
TI - Revealing and tuning the core, structure, properties and function of polymer
micelles with lanthanide-coordination complexes.
AB - Controlling self-assembly processes is of great interest in various fields where
multifunctional and tunable materials are designed. We here present the
versatility of lanthanide-complex-based micelles (Ln-C3Ms) with tunable
coordination structures and corresponding functions (e.g. luminescence and
magnetic relaxation enhancement). Micelles are prepared by charge-driven self
assembly of a polycationic-neutral diblock copolymer and anionic coordination
complexes formed by Ln(III) ions and the bis-ligand L2EO4, which contains two
dipicolinic acid (DPA) ligand groups (L) connected by a tetra-ethylene oxide
spacer (EO4). By varying the DPA/Ln ratio, micelles are obtained with similar
size but with different stability, different aggregation numbers and different
oligomeric and polymeric lanthanide(III) coordination structures in the core.
Electron microscopy, light scattering, luminescence spectroscopy and magnetic
resonance relaxation experiments provide an unprecedented detailed insight into
the core structures of such micelles. Concomitantly, the self-assembly is
controlled such that tunable luminescence or magnetic relaxation with Eu-C3Ms,
respectively, Gd-C3Ms is achieved, showing potential for applications, e.g. as
contrast agents in (pre)clinical imaging. Considering the various lanthanide(III)
ions have unique electron configurations with specific physical chemical
properties, yet very similar coordination chemistry, the generality of the
current coordination-structure based micellar design shows great promise for
development of new materials such as, e.g., hypermodal agents.
PMID- 26444313
TI - Assessing the Role of Capping Molecules in Controlling Aggregative Growth of Gold
Nanoparticles in Heated Solution.
AB - This report describes findings of an investigation of the role of capping
molecules in the size growth in the aggregative growth of pre-formed small-sized
gold nanoparticles capped with alkanethiolate monolayers toward monodispersed
larger sizes. The size controllability depends on the thiolate chain length and
concentration in the thermal solution. The size evolution in solution at
different concentrations of alkanethiols is analyzed in relation to adsorption
isotherms and cohesive energy. The size dependence on thiolate chain length is
also analyzed by considering the cohesive energy of the capping molecules,
revealing the importance of cohesive energy in the capping structure. Theoretical
and experimental comparisons of the surface plasmonic resonance optical
properties have also provided new insights into the mechanism, thus enabling the
exploitation of size-dependent nanoscale properties.
PMID- 26444314
TI - Evaluation of antibacterial activity of caffeic acid encapsulated by beta
cyclodextrins.
AB - CONTEXT: Caffeic acid is described as antibacterial, but this bioactive molecule
has some issues regarding solubility and stability to environmental stress. Thus,
encapsulation devices are required. OBJECTIVE: The aim of this work was to study
the effect of the caffeic acid encapsulation by cyclodextrins on its
antibacterial activity. MATERIALS AND METHODS: The interactions between the
caffeic acid and three cyclodextrins (beta-cyclodextrin (betaCD), 2-hydroxypropyl
beta-cyclodextrin (HPbetaCD) and methyl-beta-cyclodextrin were study. RESULTS AND
DISCUSSION: The formation of an aqueous soluble inclusion complex was confirmed
for betaCD and HPbetaCD with a 1:1 stoichiometry. The betaCD/caffeic acid complex
showed higher stability than HPbetaCD/caffeic acid. Caffeic acid antibacterial
activity was similar at pH 3 and pH 5 against the three bacteria (K. pneumoniae,
S. epidermidis and S. aureus). CONCLUSIONS: The antibacterial activity of the
inclusion complexes was described here for the first time and it was shown that
the caffeic acid activity was remarkably enhanced by the cyclodextrins
encapsulation.
PMID- 26444315
TI - Low-temperature dynamic nuclear polarization of gases in Frozen mixtures.
AB - PURPOSE: To present a new cryogenic technique for preparing gaseous compounds in
solid mixtures for polarization using dynamic nuclear polarization (DNP).
METHODS: (129) Xe and (15) N2 O samples were prepared using the presented method.
Samples were hyperpolarized at 1.42K at 5 Tesla. (129) Xe was polarized at 1.65K
and 1.42K to compare enhancement. Polarization levels for both samples and T1
relaxation times for the (129) Xe sample were measured. Sample pulverization for
the (129) Xe and controlled annealing for both samples were introduced as
additional steps in sample preparation. RESULTS: Enhancement increased by 15% due
to a temperature drop from 1.65K to 1.42K for the (129) Xe sample. A polarization
level of 20 +/- 3% for the (129) Xe sample was achieved, a two-fold increase from
10 +/- 1% after pulverization of the sample at 1.42K. T1 of the (129) Xe sample
was increased by more than three-fold by means of annealing. In the case of (15)
N2 O, annealing led to a ~two-fold increase in the signal level after DNP.
CONCLUSION: The presented technique for producing and manipulating solid
gas/glassing agent/radical mixtures for DNP led to high polarization levels in
(129) Xe and (15) N2 O samples. These methods show potential for polarizing other
gases using DNP technology. Magn Reson Med 76:1007-1014, 2016. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26444316
TI - Inhibition of soluble epoxide hydrolase activity by compounds isolated from the
aerial parts of Glycosmis stenocarpa.
AB - The aim of this study is to search for soluble epoxide hydrolase (sEH) inhibitors
from natural plants, bioassay-guided fractionation of lipophilic n-hexane and
chloroform layers of an extract of the aerial parts of Glycosmis stenocarpa led
to the isolation of 12 compounds (1-12) including murrayafoline-A (1),
isomahanine (2), bisisomahanine (3), saropeptate (4), (24 S)-ergost-4-en-3,6
dione (5), stigmasta-4-en-3,6-dion (6), stigmast-4-en-3-one (7), beta-sitosterol
(8), 24-methylpollinastanol (9), trans-phytol (10), neosarmentol III (11) and (+)
epiloliolide (12). Their structures were elucidated on the basis of spectroscopic
data. Among them, neosarmentol III (11) was isolated from nature for the first
time. All the isolated compounds were evaluated for their inhibitory activity
against sEH. Among isolated carbazole-type compounds, isomahanine (2) and
bisisomahanine (3) were identified as a potent inhibitor of sEH, with IC50 values
of 22.5 +/- 1.7 and 7.7 +/- 1.2 uM, respectively. Moreover, the inhibitory action
of 2 and 3 represented mixed-type enzyme inhibition.
PMID- 26444317
TI - Childhood Bereavement and Type 1 Diabetes: a Danish National Register Study.
AB - BACKGROUND: Death of a close family member such as a parent or a sibling can
cause prolonged stress and changes in the family structure that may have
extensive social and health effects on a young child. The aim of this paper is to
examine the rate of type 1 diabetes following bereavement due to death of a first
degree family member in early life. METHODS: We used data from the Danish Civil
Registration System (CRS) to identify singleton births in Denmark born 1 January
1980 through 31 December 2005, n = 1 740 245 and their next of kin. We
categorised children as exposed to bereavement if they lost a mother, father or
sibling from age 5 years onwards, the remaining children were considered
unexposed. Children were followed until first diagnosis of diabetes, death,
emigration, or 31 December 2010. We estimated incidence rate ratios (IRRs) from
birth using log-linear Poisson regression models with person-years as an offset
variable. Exposed children were followed up for an average of 9.1 years [standard
deviation (SD) 6.7] and unexposed children were followed up for an average of
12.3 years (SD 7.3). RESULTS: In our sample 94 943 children were exposed to
bereavement, and 6110 cases of type 1 diabetes were identified. Bereavement was
associated with an increased rate of type 1 diabetes when exposure onset began
after 11 years of age (adjusted IRR 1.28, 95% confidence interval 1.08, 1.51).
CONCLUSION: We found some evidence to indicate an increase in the rate of type 1
diabetes among children exposed to bereavement when exposure occurred after 11
years of age.
PMID- 26444318
TI - Columellar-Frenulum Angle - A Significant Clinical Parameter in Assessing the
Degree of Severity in Unilateral Cleft Lip.
AB - OBJECTIVES: The study was carried out to learn if the columellar-frenulum angle
could be used as one of the most important anthropometric measurements to predict
the clinical severity in unilateral cleft lip patients. SETTINGS AND DESIGN: This
is a prospective case series conducted at Banaras Hindu University, Varanasi,
India. METHODS AND MATERIAL: The study was based on the Thomson and Reinders
criteria (1995), and various anthropometric measurements, including the
columellar-frenulum angle, were measured. A total of 30 patients (21 boys and 9
girls) were included in the study. The ages of the children varied from 4 months
to 15 years. The left side was affected in 18 patients, and 2 gave a significant
positive family history. All the patients were subjected uniformly to Tennison's
cleft lip repair. Patients with strictly unilateral complete cleft lip and palate
were included in the study. Microform clefts, incomplete cleft lips, and
bilateral clefts were excluded from the study. STATISTICAL ANALYSIS: The data was
analyzed using Pearson's correlation coefficient. RESULTS: The CF angle
correlated negatively with the soft tissue defect of the cleft, cutaneous lip
length, and vermilion lip length discrepancies from normal and soft tissue width
just behind the alveolus. CONCLUSIONS: CF angle promises to offer a method by
which prognosis of clefts can be predicted in terms of its severity in patients
with unilateral cleft lip.
PMID- 26444319
TI - Assessing the Interdental Septal Thickness in Alveolar Bone Grafting Using Cone
Beam Computed Tomography.
AB - OBJECTIVE: To assess the interdental septal thickness of grafted bone bridges
using cone beam computed tomography (CBCT). PATIENTS: Of 71 patients with cleft
lip and/or palate having undergone alveolar bone grafting for the first time at
least 6 months previously, 52 patients with 57 grafted sites rated type I or II
based on the Bergland scale using occlusal radiographs were selected.
INTERVENTIONS: CBCT was performed for each bone-grafted alveolar cleft within 1
week after the occlusal radiographs were taken. MAIN OUTCOME MEASURES: The
thickness of the grafted bone bridge was evaluated using CBCT according to the
relationship between crest thickness and the root width of cleft-adjacent teeth,
and the results were classified into four categories, with scores of 1 to 4
indicating that the thickness of the bony bridge was >=100%, >=75%, >=50%, and
<50% of the root width of the cleft-adjacent teeth, respectively. RESULTS: Of the
34 grafted sites rated type I on the Bergland scale, 15 (44.12%), 10 (29.41%), 4
(11.76%), and 5 (14.71%) clefts were scored 1 to 4 on interdental septal
thickness using CBCT, respectively. Of the 23 cases of type II, 3 (13.04%), 9
(39.13%), 1 (3.45%), and 10 (43.48%) clefts were scored 1 to 4, respectively.
CONCLUSIONS: The interdental septal thickness of grafted bone bridges with
clinically successful heights based on the Bergland scale (type I or II) using
occlusal radiographs varied significantly in the evaluation using CBCT.
PMID- 26444320
TI - Subacute Cutaneous Lupus Erythematosus Induced by Mitotane.
PMID- 26444321
TI - Intrapartum sonographic signs: new diagnostic tools in malposition and
malrotation.
AB - In the past years, numerous studies have been published on the use of ultrasound
during labor, showing this is an effective, accurate and objective tool for the
assessment of the fetal head position and station. Literature affirmed that
traditional transvaginal digital examination is highly subjective and dependent
on the operator's experience. On the contrary, the use of intrapartum suprapubic
transabdominal ultrasound can improve accuracy in determination of fetal head
position and the precise knowledge of the location of specific fetal head
landmarks in relationship to maternal pelvis. Intrapartum ultrasound will assist
obstetricians in the diagnosis of normal labor progression, suggesting when
medical and or operative intervention should be taken in case of complications.
During each fetal head movement, there is a very specific relationship between
fetal head landmarks and well-identified maternal structures, so the ultrasound
diagnosis is performed step by step. In this review, we summarized the clinical
situation of the fetal head in the pelvis and the relative ultrasonographic
signs. Moreover, we collected all the ultrasonographic measures to diagnose the
fetal head progression and rotations in the birth canal.
PMID- 26444322
TI - Patient-Reported Health in Young People With Congenital Heart Disease
Transitioning to Adulthood.
AB - PURPOSE: Because life expectancy of patients with congenital heart disease (CHD)
has increased substantially, assessment of patient-reported health is seen as an
important component in the follow-up. Therefore, we (1) examined patient-reported
health status of young people with CHD from a longitudinal perspective; (2)
compared patient-reported health of patients with that of controls from the
general population; and (3) investigated longitudinal interrelationships among
various domains of patient-reported health. METHODS: We included 429 patients
with CHD (aged 14-18 years) in a longitudinal study with four measurement points.
Patient-reported health status was measured using a linear analog scale for self
rated health and the Pediatric Quality of Life Inventory (PedsQL). RESULTS: Self
rated health was good, with mean scores that slightly decreased from 81.78 to
78.90 from Time 1 to Time 4. PedsQL scores were also good, with the highest
scores obtained for physical functioning. Patients with mild heart defects
consistently reported higher scores on self-rated health and PedsQL than the
general population. The scores of patients with complex heart defects were
generally lower than those of the general population. Cross-lagged path analyses
demonstrated that symptoms, cognitive functioning, and communication problems
constituted the most consistent predictors of perceived health domains over time.
CONCLUSIONS: Patient-reported health was considerably good. Domains of patient
reported health that deserve specific attention are symptoms, cognitive
functioning, and communication problems. Intervening in these three domains may
yield indirect benefits on other health status domains and may improve the
overall perceived health status of young people with CHD.
PMID- 26444323
TI - Reducing LDL with PCSK9 Inhibitors--The Clinical Benefit of Lipid Drugs.
PMID- 26444324
TI - Nonmedical Uses of Antibiotics: Time to Restrict Their Use?
AB - The global crisis of antibiotic resistance has reached a point where, if action
is not taken, human medicine will enter a postantibiotic world and simple
injuries could once again be life threatening. New antibiotics are needed
urgently, but better use of existing agents is just as important. More
appropriate use of antibiotics in medicine is vital, but the extensive use of
antibiotics outside medical settings is often overlooked. Antibiotics are
commonly used in animal husbandry, bee-keeping, fish farming and other forms of
aquaculture, ethanol production, horticulture, antifouling paints, food
preservation, and domestically. This provides multiple opportunities for the
selection and spread of antibiotic-resistant bacteria. Given the current crisis,
it is vital that the nonmedical use of antibiotics is critically examined and
that any nonessential use halted.
PMID- 26444325
TI - Eldecalcitol (ED-71), an analog of 1alpha,25-dihydroxyvitamin D3 as a potential
anti-cancer agent for oral squamous cell carcinomas.
AB - We have previously reported that 1,25(OH)2D3 inhibits NF-kappaB activity and thus
inhibits growth of OSCC cells in serum-free culture and down-regulates
HBp17/FGFBP-1 expression, which is important for cancer cell growth and
angiogenesis. Here, we have investigated the effects of ED-71, an analog of
vitamin D3 (VD) on OSCC cell lines in serum-free culture. It is known that ED-71
has a stronger inhibitory effect on bone resorption compared to VD and other VD
analogs. To the best of our knowledge, there was no report examining the
potential of ED-71 as an anti-cancer agent for OSCC. We found that ED-71 is able
to inhibit the growth of cancer cell lines at a concentration of hundred times
lower than calcitriol. As Cyp24A1 was reportedly induced in cancer cells, we
measured the expression of CYP24A1 in OSCC cell lines (NA and UE), A431
epidermoid carcinoma and normal fibroblast cell (gfi) in serum-free culture. As a
result, CYP24A1 mRNA and the protein expression in the OSCC cells treated with ED
71 increased in a dose-dependent manner. However, in vivo experiment, in which
the A431 cells were implanted in mice, tumor formation was reduced by the ED-71
treatment with no significant difference between Cyp24A1 expression in the tumors
of ED-71-treated and control group, as analyzed by western blotting and
immunohistochemistry. These results suggest that ED-71 is a potential anti-cancer
agent for OSCC.
PMID- 26444326
TI - Factors associated with surgical management in an underinsured, safety net
population.
AB - BACKGROUND: Few studies include significant numbers of racial and ethnic minority
patients. The current study was performed to examine factors that affect breast
cancer operations in an underinsured population. METHODS: We performed a
retrospective review of all breast cancer patients from January 2010 to May 2012.
Patients with American Joint Committee on Cancer clinical stage 0-IIIA breast
cancer underwent evaluation for type of operation: breast conservation,
mastectomy alone, and reconstruction after mastectomy. RESULTS: The population
included 403 patients with mean age 53 years. Twelve of the 50 patients (24%)
diagnosed at stage IIIB presented with synchronous metastatic disease. Of the
remaining patients, only 2 presented with metastatic disease (0.6%). The initial
operation was 65% breast conservation, 26% mastectomy alone, and 10%
reconstruction after mastectomy. Multivariate analysis revealed that Hispanic
ethnicity (odds ratio [OR], 0.38; 95% CI, 0.19-0.73; P = .004), presentation with
palpable mass (OR, 0.34; 95% CI, 0.13-0.90; P = .03), preoperative chemotherapy
(OR, 0.25; 95% CI, 0.10-0.62; P = .003) were associated with a lesser likelihood
of mastectomy. Multivariate analysis of factors associated with reconstruction
after mastectomy showed that operation with Breast surgical oncologist (OR, 18.4;
95% CI, 2.18-155.14; P < .001) and adequate health literacy (OR, 3.13; 95% CI,
0.95-10.30; P = .06) were associated with reconstruction. CONCLUSION: The
majority of safety net patients can undergo breast conservation despite delayed
presentation and poor use of screening mammography. Preoperative chemotherapy
increased the likelihood of breast conservation. Routine systemic workup in
patients with operable breast cancer is not indicated.
PMID- 26444327
TI - Diaphragm pacing system implanted in a patient with ALS.
AB - The diaphragm pacing system (DPS) is a life quality improving operation in
amyotrophic lateral sclerosis (ALS) patients who need mechanical ventilation or
have chronic respiratory insufficiency. This procedure is gaining in popularity,
and the number of centers implanting diaphragm pacing systems (DPS) is
increasing. DPS delays the need for a ventilation machine in the early stages of
Amyotrophic lateral sclerosis (ALS) disease. In this case study, we present a
young female ALS patient. A DPS was implanted after respiratory insufficiency
began. In the one-year follow-up period following her operation, her need for
ventilatory support disappeared.
PMID- 26444328
TI - The effects of neuromuscular electrical stimulation at different frequencies on
the activations of deep abdominal stabilizing muscles.
AB - BACKGROUD: Low back pain is associated with transversus abdominis (TrA)
dysfunction. Recently, it was proposed that Neuromuscular Electrical Stimulation
(NMES) could be used to stimulate deep abdominal muscle contractions and improve
lumbopelvic stability. OBJECTIVE: The purpose of this study was to determine the
optimal stimulation frequency required during NMES for the activation of deep
abdominal muscles. METHODS: Twenty healthy volunteers between the ages of 24 and
32 were included. The portable research-stimulator was applied using a 10 second
contraction time, and a 10 second resting time at 20 Hz, 50 Hz, and 80 Hz.
Changes in muscle thicknesses were determined for the TrA, obliquus internus
(OI), and obliquus externus (OE) by real time ultrasound imaging. RESULTS:
Significant thickness increases in the TrA, OI, and OE were observed during NMES
versus the resting state (p < 0.05). Of the frequencies examined, 50 Hz NMES
produced the greatest increase in TrA thickness (1.33 fold as compared with 1.22
fold at 20 Hz and 1.21 fold at 80 Hz) (p < 0.05). CONCLUSIONS: Our results
indicate that NMES can preferentially stimulate contractions in deep abdominal
stabilizing muscles. Most importantly, 50 Hz NMES produced greater muscle
thickness increases than 20 or 80 Hz.
PMID- 26444329
TI - Measurement of lumbar spine intervertebral motion in the sagittal plane using
videofluoroscopy.
AB - BACKGROUND: Static radiographic techniques are unable to capture the wealth of
kinematic information available from lumbar spine sagittal plane motion.
OBJECTIVE: Demonstration of a viable non-invasive technique for acquiring and
quantifying intervertebral motion of the lumbar spine in the sagittal plane.
METHODS: Videofluoroscopic footage of sagittal plane lumbar spine flexion
extension in seven symptomatic volunteers (mean age = 48 yrs) and one
asymptomatic volunteer (age = 54 yrs) was recorded. Vertebral bodies were
digitised using customised software employing a novel vertebral digitisation
scheme that was minimally affected by out-of-plane motion. RESULTS: Measurement
errors in intervertebral rotation (+/- 1 degrees ) and intervertebral
displacement (+/- 0.5 mm) compare favourably with the work of others. Some
subjects presenting with an identical condition (disc prolapse) exhibited a
similar column vertebral flexion-extension relative to S1 (L3: max. 5.9 degrees ,
min. 5.6 degrees ), while in others (degenerative disc disease) there was
paradoxically a significant variation in this measurement (L3: max. 28.1 degrees
, min. 0.7 degrees ). CONCLUSIONS: By means of a novel vertebral digitisation
scheme and customised digitisation/analysis software, sagittal plane
intervertebral motion data of the lumbar spine data has been successfully
extracted from videofluoroscopic image sequences. Whilst the intervertebral
motion signatures of subjects in this study differed significantly, the available
sample size precluded the inference of any clinical trends.
PMID- 26444330
TI - Efficacy of low-level laser therapy associated to orthoses for patients with
carpal tunnel syndrome: A randomized single-blinded controlled trial.
AB - OBJECTIVE: Compare the efficacy of orthoses and patient education with and
without the addition to Low-Level Laser Therapy (LLLT - 660 nm, 30 mW, a
continuous regime and bean area of 0.06 cm2). The laser irradiation was delivered
with the fluency of 10J/cm2 in patients with mild and moderate Carpal Tunnel
Syndrome (CTS). METHODS: 48 patients were randomized and 30 finished the protocol
(a sample loss of 37.5%), 90% female and 10% males. Randomization was applied to
allocate the patients in each one of the groups, with association or not to LLLT
(group orthoses or LLLT and orthoses). All of them were submitted to ergonomic
home orientations. The short-term symptoms and function outcome were assessed
through: Boston Carpal Tunnel Questionnaire (BCTQ) - Severity of Symptoms (SS)
Functional Score (FS). Pain (VAS), Semmes-Weinstein monofilaments, 2PD and pinch
strength was used for characterization of the sample. Most of the participants
were women, over 4th decade enrolled on heavy hand duties occupations, right
handed, 66.7% affected on dominant hand, without alterations in sensory median
nerve thresholds or pinch strength. RESULTS: Both groups showed a reduction of
total BCTQ score and its subdomains after six weeks, with significant difference
(p< 0.05), comparing to baseline. No significant difference was found between
groups. A Minimal clinical change was observed after the intervention in 92.3% of
participants for BCTQ subdomain severity of symptoms at individual comparison for
LLLT and orthoses group and 76.5% for the orthoses group, demonstrating clinical
relevance. Effect size Cohen's index was moderate for the severity of symptoms.
CONCLUSION: LLLT in association to orthoses and ergonomic orientation seems to be
effective in short-term symptoms relieve for patients with mild and moderate CTS.
PMID- 26444331
TI - Associations between phenotypes of preeclampsia and thrombophilia.
AB - OBJECTIVES: Preeclampsia complicates 2-8% of all pregnancies. Studies on the
association of preeclampsia with thrombophilia are conflicting. Clinical
heterogeneity of the disease may be one of the explanations. The present study
addresses the question whether different phenotypes of preeclampsia are
associated with thrombophilia factors. Study design We planned a retrospective
cohort study. From 1985 until 2010 women with preeclampsia were offered
postpartum screening for the following thrombophilia factors: anti-phospholipid
antibodies, APC-resistance, protein C deficiency and protein S deficiency,
hyperhomocysteineamia, factor V Leiden and Prothrombin gene mutation. Hospital
records were used to obtain information on phenotypes of the preeclampsia and
placental histology. RESULTS: We identified 844 women with singleton pregnancies
who were screened for thrombophilia factors. HELLP complicated 49% of
pregnancies; Fetal growth restriction complicated 61% of pregnancies. Early
delivery (<34th week) occurred in 71% of pregnancies. Any thrombophilia factor
was present in 29% of the women. Severe preeclampsia was associated with protein
S deficiency (p=0.01). Fetal growth restriction was associated with anti
phospholipid antibodies (p<0.01). Early onset preeclampsia was associated with
anti-phospholipid antibodies (p=0.01). Extensive placental infarction (>10%) was
associated with anti-phospholipid antibodies (p<0.01). Low placental weight (<5th
percentile) was associated with hyperhomocysteineamia (p=0.03). No other
associations were observed. CONCLUSIONS: Early onset preeclampsia, especially if
complicated by fetal growth restriction, are associated with anti-phospholipid
antibodies. Other phenotypes of preeclampsia, especially HELLP syndrome, were not
associated with thrombophilia. We advise only to test for anti-phospholipid
antibodies after early onset preeclampsia, especially if complicated by fetal
growth restriction. We suggest enough evidence is presented to justify no further
studies are needed.
PMID- 26444332
TI - Mouse preantral follicle development in two-dimensional and three-dimensional
culture systems after ovarian tissue vitrification.
AB - OBJECTIVES: This work on follicle culture and evaluation of expression of oocyte
maturation genes helps to better understand the complicated processes of
folliculogenesis and to develop new approaches for infertility treatment. STUDY
DESIGN: Ovaries of 12-day-old female NMRI mice were divided into control and
vitrification groups. After vitrification and warming procedures, ovarian tissue
morphologies were histologically evaluated and compared to those of the control
group. In the second stage, preantral follicles were mechanically isolated from
non-vitrified and vitrified ovaries and cultured for 12 days in two-dimensional
(2D) and three-dimensional (3D) systems. Finally, the survival and growth rate of
follicles and quantitative expression of oocyte maturation genes (Gdf9, Bmp15 and
Bmp6) were studied. RESULT: Morphological integrity of ovarian tissue in
vitrification group was well preserved. Survival rates of cultured preantral
follicles in control group during 2D and 3D systems were somewhat similar, but
were significantly different between 2D and 3D systems in vitrification group.
Although the growth rate of follicles was similar in the 3D system in both
groups, substantially higher growth rate was observed for the control group in
the 2D system. Expressions of oocyte maturation genes were, to some extent,
similar between control and vitrification groups. There was a remarkable
reduction in expression pattern of genes in 3D compared to 2D system in both
experimental groups, during the 12th day of culture period. CONCLUSIONS: 3D in
vitro culture system could be appeared more appropriate than 2D culture system
for preservation of follicles in terms of spatial morphology, growth rate and
expression reduction of maturation genes.
PMID- 26444333
TI - Capillary electrophoresis coupled with 1,1'-thiocarbonyldiimidazole
derivatization for the rapid detection of total homocysteine and cysteine in
human plasma.
AB - A simple and rapid approach is described for the determination of total plasma
cysteine and homocysteine using capillary electrophoresis. Human plasma samples
were reduced with dithiothreitol and then processed with 1,1'
thiocarbonyldiimidazole in acetonitrile. After centrifugation, the sample
supernatant was injected directly into a capillary by applying negative voltage
and analytes were stacked after alkaline post-injection. Using a 50MUm i.d.
silica capillary of 35cm total length, filled with 0.1M triethanolamine, 0.15M
formic acid, and 50MUM hexadecyltrimethylammonium bromide (pH 3.9), we reached a
limit of quantification of 2.5MUM for homocysteine. Accuracy was 94.7-105.1%,
intra- and inter-day imprecisions were <2.5 and <3%, respectively. The total
analysis time was 6min. Furthermore, liquid-phase extraction with isopropanol led
to a fourfold increase in sensitivity.
PMID- 26444334
TI - Development and validation of an improved HPLC-MS/MS method for comparative
pharmacokinetics of penehyclidine hydrochloride following a single intravenous or
intramuscular injection.
AB - Penehyclidine hydrochloride (PHC) is an anticholinergic drug with both
antimuscarinic and antinicotinic activity. In order to compare the
pharmacokinetics of two administration routes (intravenous injection (i.v.) and
intramuscular injection (i.m.)) of PHC, an improved High Performance Liquid
Chromatography Tandem Mass Spectrometry (HPLC-MS/MS) bioanalytical method was
developed for the quantification of PHC in plasma and urine using verapamil as
the internal standard (I.S.). Chromatography was performed using a Thermo
Hypersil GOLD column (30mm*2.1mm, 3MUm), with a gradient elution of 10/00 formic
acid-10mmol/L ammonium acetate and acetonitrile at 0.3mL/min. Detection and
quantitation were performed by electrospray ionization (ESI) and multiple
reaction monitoring (MRM) in the positive ion mode. The most intense [M+H](+) MRM
transition of PHC at m/z 316.2->128.3 was used for PHC quantitation, and the
transition at m/z 454.6->303.2 was used to monitor I.S. The lower limit of
quantification (LLOQ) was 0.05 ng/mL. The intraday precision was <6.71% and the
interday precision was <11.69%. The pharmacokinetic parameters of i.v. and i.m.
administration routes were as follows (i.v. vs i.m.): t1/2 15.73 vs 17.24h, Tmax
0.06 vs 0.26h, AUC0-t 69.35 vs 67.90hng/mL, AUC0-inf 78.24 vs 79.67hng/mL, Cmax
37.5 vs 9.1ng/mL, Ae0-24h 22.7 vs 25.21MUg. There were no significant differences
between parameters t1/2 and AUC (P>0.05), but significant differences were
observed in Cmax, Tmax and Ae0-24h between the two administration routes
(P<0.05). The mean absolute bioavailability of the i.m. administration route was
98.4% (95% confidence interval, 93.4-103.6%). Safety results showed that PHC
appeared to be well tolerated in both i.v. and i.m. administration routes and
pharmacokinetic results showed that PHC was nearly completely absorbed via i.m.
administration route.
PMID- 26444335
TI - Method development for quantification of the environmental neurotoxin annonacin
in Rat plasma by UPLC-MS/MS and application to a pharmacokinetic study.
AB - Annonacin is an environmental neurotoxin identified in the pulp of several fruits
of the Annonaceae family (for example in Annona muricata, Asimina triloba), whose
consumption was linked with the occurrence of sporadic atypical Parkinsonism with
dementia. Pharmacokinetic parameters of this molecule are unknown. A method for
its quantification in Rat plasma was developed, using its analogue annonacinone
as an internal standard. Extraction from plasma was performed using ethylacetate
with a good recovery. Quantification was performed by UPLC-MS/MS in SRM mode,
based on the loss of the gamma-methyl-gamma-lactone (-112amu) from the sodium
cationized species [M+Na](+) of both annonacin and internal standard. The limit
of quantification was 0.25ng/mL. Despite strong matrix effects, a good linearity
was obtained over two distinct ranges 0.25-10ng/mL and 10-100ng/mL. The intra-
and inter-day precisions (RSD) were lower than 10%, while accuracy was within +/
10%. This method was applied to a pharmacokinetic study in the Rat. After oral
administration of 10mg/kg annonacin, a Cmax of 7.9+/-1.5ng/mL was reached at Tmax
0.25h; T1/2 was 4.8+/-0.7h and apparent distribution volume was 387.9+/-64.6L.
The bioavailability of annonacin was estimated to be 3.2+/-0.3% of the ingested
dose.
PMID- 26444337
TI - Phenyliodine(III) Diacetate Mediated Oxidative Cyclization of 1-Alkenoyl-1
carbamoyl Cycloalkanes: Access to Spiro-Fused Dihydrofuran-3(2H)-ones.
AB - Facile and efficient synthesis of spiro-fused dihydrofuran-3(2H)-ones was
developed via phenyliodine(III) diacetate (PIDA) mediated oxidative cyclization
of 1-alkenoyl-1-carbamoyl cycloalkanes under very mild conditions.
PMID- 26444336
TI - Graphitic carbon nitrides modified hollow fiber solid phase microextraction for
extraction and determination of uric acid in urine and serum coupled with gas
chromatography-mass spectrometry.
AB - An elevated uric acid (UA) in urine or serum can affect renal function and blood
pressure, which is an indicator of gout, cardiovascular and renal diseases,
hypertension, etc. In this work, a new type of mixed matrix membrane (MMM), based
on graphitic carbon nitrides (g-CNs) and hollow fiber (HF), was prepared and
combined with solid phase microextraction (SPME) mode to determine UA in urine
and serum followed by gas chromatography-mass spectrometry (GC/MS). The porous g
CNs were dispersed in ammonia, and then the exfoliated g-CNs nanosheets were held
in the pores of HF by capillary forces and sonification. The prepared g-CNs
modified HF (g-CNs-HF) was immersed in biofluid directly to extract UA with SPME
mode and the solvent-free mode is convenient for further derivatization and
analysis. To achieve the highest extraction efficiency (EF), main extraction and
derivatization parameters, such as g-CNs-HF immobilizing time, sonification power
and time of extraction, derivatization and desorption time, were optimized. Under
the optimum extraction conditions, a favorable linearity of UA was obtained in
the range 0.1-200MUgmL(-1) with correlation coefficients higher than 0.9990, and
the average recoveries at three spiked levels of UA in urine and serum ranged
from 80.7% to 121.6%, from 84.7% to 101.1%, respectively. The obtained results
demonstrated the developed g-CNs-HF-SPME is a simple, rapid, cost-effective,
solvent-free method for the analysis of UA in biofluid.
PMID- 26444338
TI - In vitro cytotoxicity evaluation of different pulp capping materials: a
comparative study.
AB - Direct pulp capping covers the exposed surface of the pulp to maintain its
vitality and preserve its functional and biologic activity. The aim of the
present study was to compare the biocompatibility effects of seven different pulp
capping materials in vitro: Dycal(r), Calcicur(r), Calcimol LC(r), TheraCal
LC(r), ProRoot MTA(r), MTA-Angelus(r), and Biodentine(r). Using the Transwell
insert methodology by Alamar blue test, we evaluated the cytocompatibility of the
above mentioned materials towards murine odontoblasts cells (MDPC-23) at three
different times (24, 48, and 72 h). For additional control, the cell viability at
72 hours was also assessed by MTT assay. Morphological analysis of murine
odontoblasts was assessed by Confocal Laser Scanning Microscope. The results
indicate significantly different biocompatibility among materials with different
composition. Biodentine(r) and mineral trioxide aggregate (MTA)-based products
showed lower cytotoxicity, varying from calcium hydroxide-based materials, which
exhibited higher cytotoxicity. Although our findings are limited to in vitro
conditions, the observation that Biodentine(r) caused a cytotoxic effect similar
to MTA suggests that it may be considered an alternative in pulp-capping
treatment, as calcium hydroxide-based materials present higher cytotoxic effects.
PMID- 26444339
TI - Acute toxicity of maneb in the tadpoles of common and green toad.
AB - Pesticides used in agriculture can have hazardous effects on aquatic organisms,
and amphibians are even more threatened than other aquatic vertebrates. Maneb is
widely used to control fungal diseases on crops, fruits, and vegetables. The aim
of this study was to investigate the acute toxic effects of maneb on the common
(Bufo bufo) and green toad (Pseudepidalea viridis) tadpoles. Tadpoles at the
development stage 21 were exposed to maneb (0-5 mg L(-1)) for 120 h. Maneb LC50
values at hour 120 were 1.966 mg L(-1) for B. bufo and 0.332 mg L-1 for P.
viridis. To the best of our knowledge, these are the first published LC50
findings for the two species. Visceral oedema and tail deformations were observed
in both species. We also observed liver necrosis, pronephric tubule deformations,
somite deteriorations, and visceral oedema at maneb concentrations>=0.1 mg L(-1)
for B. bufo and >=0.05 mg L(-1) for P. viridis. Our results show that B. bufo
tadpoles have a much higher resilience to maneb than P. viridis tadpoles. This
resilience seems to be related to the larger size of the B. bufo tadpoles and
their ability to metamorphose faster in adverse conditions. Future research
should look into the mechanisms of toxic action of maneb in anurans.
PMID- 26444340
TI - Quantitative analysis of arbutin and hydroquinone in strawberry tree (Arbutus
unedo L., Ericaceae) leaves by gas chromatography-mass spectrometry.
AB - The phenolic glycoside arbutin and its metabolite with uroantiseptic activity
hydroquinone occur naturally in the leaves of various medicinal plants and
spices. In this study, an extraction procedure coupled with gas chromatography
mass spectrometry (GC-MS) was developed to determine arbutin and hydroquinone
content in strawberry tree (Arbutus unedo L., Ericaceae) leaves. The method
showed good linearity (R2>0.9987) in the tested concentration range (0.5-200 MUg
mL(-1)), as well as good precision (RSD<5%), analytical recovery (96.2-98.0%),
and sensitivity (limit of detection=0.009 and 0.004 MUg mL(-1) for arbutin and
hydroquinone, respectively). The results obtained by the validated GC-MS method
corresponded well to those obtained by high performance liquid chromatography
(HPLC) method. The proposed method was then applied for determining arbutin and
hydroquinone content in methanolic leaf extracts. The amount of arbutin in the
leaves collected on the island of Kolocep (6.82 mg g(-1) dry weight) was found to
be higher (tpaired=43.57, tc=2.92) in comparison to the amount of arbutin in the
leaves collected on the island of Mali Losinj (2.75 mg g(-1) dry weight).
Hydroquinone was not detected in any of the samples. The analytical features of
the proposed GC-MS method demonstrated that arbutin and hydroquinone could be
determined alternatively by gas chromatography. Due to its wide concentration
range, the method could also be suitable for arbutin and hydroquinone analysis in
leaves of other plant families (Rosaceae, Lamiaceae, etc.).
PMID- 26444341
TI - Assessment of exposure to the Penicillium glabrum complex in cork industry using
complementing methods.
AB - Cork oak is the second most dominant forest species in Portugal and makes this
country the world leader in cork export. Occupational exposure to Chrysonilia
sitophila and the Penicillium glabrum complex in cork industry is common, and the
latter fungus is associated with suberosis. However, as conventional methods seem
to underestimate its presence in occupational environments, the aim of our study
was to see whether information obtained by polymerase chain reaction (PCR), a
molecular-based method, can complement conventional findings and give a better
insight into occupational exposure of cork industry workers. We assessed fungal
contamination with the P. glabrum complex in three cork manufacturing plants in
the outskirts of Lisbon using both conventional and molecular methods.
Conventional culturing failed to detect the fungus at six sampling sites in which
PCR did detect it. This confirms our assumption that the use of complementing
methods can provide information for a more accurate assessment of occupational
exposure to the P. glabrum complex in cork industry.
PMID- 26444342
TI - Levels of house dust mite allergen in cars.
AB - This small study investigated house dust mite (HDM) allergen levels in cars and
their owners' homes in north-east Scotland. Dust samples from twelve households
and cars were collected in a standardised manner. The dust samples were extracted
and measured for the Dermatophagoides group 2 allergens (Der p 2 and Der f 2) and
total soluble protein. Allergen levels at homes tended to be higher than in the
cars, but not significantly. However, they significantly correlated with paired
car dust samples expressed either per unit weight of dust or soluble protein
(rho=0.657; p=0.02 and 0.769; p=0.003, respectively). This points to house-to-car
allergen transfer, with the car allergen levels largely reflecting levels in the
owner's home. Car HDM allergen levels were lower than those reported in Brazil
and the USA. Twenty-five percent of the houses and none of the cars had allergen
levels in dust greater than 2000 ng g(-1). This value is often quoted as a
threshold for the risk of sensitisation, although a number of studies report
increased risk of sensitisation at lower levels. This small study does not allow
for characterisation of the distribution of HDM allergen in vehicles in this
geographic area, or of the likely levels in other warmer and more humid areas of
the UK. Cars and other vehicles are an under-investigated micro-environment for
exposure to allergenic material.
PMID- 26444343
TI - Accidental discovery of asbestos-related occupational pleural disease in
unemployed carpenter: a healthcare safety net that needs mending.
AB - Unemployed persons are often on the margins of the healthcare system and under
the radar of safety and health organisations, as no systematic records are kept
of occupational diseases caused by exposure at previous work place. Law in
Slovenia requires that asbestos-related occupational diseases are verified by
establishing the causal relationship between exposure at work and its effect on
the worker. This report describes a case of verifying occupational pleural
disease in an unemployed carpenter who was referred for consultation with
occupational health specialist as part of the regular procedure for the
unemployed registered at the Employment Service of Slovenia. At the consultation
it turned out that the carpenter had been exposed to asbestos when he worked as a
teenage apprentice. The diagnosis of the bilateral pleural disease and asbestosis
was confirmed by X-ray and high-resolution computed tomography. Because he had no
record of exposure in that period, we analysed his past working environment for
minerals and found chrysotile in all asbestos board samples. The case was
presented to an interdisciplinary committee, which verified his disease as
occupational. This case points to the need of adopting guidelines for
occupational health specialists providing counsel to the national employment
service so that the number of unrecorded occupational diseases is minimised and
their treatment is covered by the state.
PMID- 26444344
TI - Hydroxyethyl starch should not be used to manage severe aluminium phosphide
poisoning.
PMID- 26444345
TI - Response to Professor Rumboldt's reaction to our letter on hydroxyethyl starch
use in managing aluminium phosphide poisoning.
PMID- 26444346
TI - The 2nd Croatian Symposium on Membrane Transporters (2. hrvatski simpozij o
transporterima): Membrane Transporters in Toxicological and Pharmacological
Research.
PMID- 26444347
TI - Brown-Vialetto-Van Laere syndrome: two siblings with a new mutation and dramatic
therapeutic effect of high-dose riboflavin.
AB - Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare and severe neurometabolic
disease. We present two siblings with BVVLS with a novel homozygous mutation in
SLC52A3 (formerly C20orf54) gene. The first sibling was admitted with respiratory
insufficiency and required mechanical ventilation. After administration of a high
dose of riboflavin, all his clinical symptoms were resolved, which also strongly
suggested the diagnosis of BVVLS. The second sibling was also found to have the
same genetic mutation as her brother. Although she was symptom-free, riboflavin
was initiated empirically. On follow-up, she developed no neurologic or metabolic
problems with entirely normal growth and development. BVVLS should be considered
in the differential diagnosis of unexplained neurologic symptoms such as
polyneuropathy and respiratory insufficiency, as BVVLS and multiple acyl-CoA
dehydrogenation defect have broadly overlapping symptoms. Furthermore, our cases
once again suggest that with proper diagnosis and early high-dose riboflavin
treatment, complete reversal of neurologic deficits in BVVLS is possible.
PMID- 26444348
TI - Entorhinal cortex: a good biomarker of mild cognitive impairment and mild
Alzheimer's disease.
AB - Entorhinal cortex (EC), thought to be the location of the earliest lesions in
Alzheimer's disease (AD), has been widely studied in recent years. With the
irreversible pathological changes of AD, there is an urgent need to find
biomarkers that can be used to predict the presence of the disease before it is
clinically expressed. The aim of this review is to summarize and analyze recent
findings that are relevant to the important role of EC in the diagnosis of mild
cognitive impairment (MCI) and mild AD and to describe a range of neuroimaging
techniques used to define the EC boundary. A comprehensive literature search for
articles published up to May 2015 was performed. Our research highlights the
finding that atrophy in EC reflects the early pathological changes of AD and can
be a strong predictor of prodromal AD. The early changes in EC are a good imaging
biomarker that can be used to discriminate individuals with MCI from normal
control subjects. A larger degree of atrophy in EC predicts increased disease
severity, and the right EC in patients with mild AD exhibited greater changes
than the left side. In addition, the EC seems to have an obvious advantage over
the hippocampus as a biomarker when predicting future conversion to AD in
individuals with MCI, and it may be of help in following the course of disease
progression. In this review, we also summarize the main differences observed
between the hippocampus and the EC when differentiating diseases. These findings
will hopefully provide an opportunity for the effective prevention and early
treatment of AD.
PMID- 26444349
TI - The bridge between two worlds: psychoanalysis and fMRI.
AB - In recent years, a connection between psychoanalysis and neuroscience has been
sought. The meeting point between these two branches is represented by
neuropsychoanalysis. The goal of the relationship between psychoanalysis and
neuroscience is to test psychoanalytic hypotheses in the human brain, using a
scientific method. A literature search was conducted on May 2015. PubMed and
Scopus databases were used to find studies for the inclusion in the systematic
review. Common results of the studies investigated are represented by a
reduction, a modulation, or a normalization of the activation patterns found
after the psychoanalytic therapy. New findings in the possible and useful
relationship between psychoanalysis and neuroscience could change the modalities
of relating to patients for psychoanalysts and the way in which neuroscientists
plan their research. Researchers should keep in mind that in any scientific
research that has to do with people, neuroscience and a scientific method cannot
avoid subjective interpretation.
PMID- 26444350
TI - Selective nematocidal effects of essential oils from two cultivated Artemisia
absinthium populations.
AB - Essential oils (EOs) obtained from two crops and populations of thujone-free
cultivated Artemisia absinthium were tested against two nematode models, the
mammalian parasite Trichinella spiralis, and the plant parasitic root knot
nematode Meloidogyne javanica. The EOs were characterized by the presence of (Z)
epoxyocimene and chrysanthenol as major components and showed time and population
dependent quantitative and qualitative variations in composition. The EOs showed
a strong ex vivo activity against the L1 larvae of the nematode Trichinella
spiralis with a reduction of infectivity between 72 and 100% at a dose range of
0.5-1 mg/ml in absence of cytotoxicity against mammalian cells. Moreover, the in
vivo activity of the EO against T. spiralis showed a 66% reduction of intestinal
adults. However, these oils were not effective against M. javanica.
PMID- 26444351
TI - Salivary alpha-Amylase And Chromogranin A In Anxiety-Related Research.
AB - Salivary alpha-amylase (sAA) and chromogranin A (sCgA) are at the forefront of
current biochemical research on anxiety. Their use is being driven by the sudden
surge of interest in "salivaomics," a new field in medicine studying saliva's
genetic code, proteome and methabolom. Interestingly, it is not the primary
functions of the enzyme and the protein, but the ingenious capture of their
secondary ones (maintenance of the acid-alkaline balance and bactericidal /
antifungal action) that allows for a swift, precise and pain-free measurement
under physical and mental duress. Upon stimulation, sAA and sCgA are almost
simultaneously released. Studying them allows a closer look at the autonomic
nervous system (ANS) as opposed to the hypothalamic-pituitary-adrenal axis (HPA),
which involves a long cascade of complex, hard to measure and interpret bio
chemical reactions.
PMID- 26444352
TI - Bone And Soft Tissue Changes In Patients With Spinal Cord Injury And Multiple
Sclerosis.
AB - In patients with spinal cord injury and multiple sclerosis, deterioration of body
composition (changes in bone, fat and muscle mass) is associated with increased
risk for diseases such as coronary artery heart disease, non-insulin dependent
diabetes mellitus, lipid metabolism abnormalities, and osteoporotic fractures in
these patients. Immobility leads to a changing pattern of loading in the
paralyzed areas, and secondary alteration in structure. However, bone and soft
tissue changes in these patients are usually neglected. The purpose of this
article is to update on the pathophysiological mechanisms leading to bone and
soft tissue changes, and to increase the awareness of the treating physicians
with respect to bone, muscle and fat loss and their consequences aiming to obtain
measures to prevent bone and soft tissue loss in these patients.
PMID- 26444353
TI - Clinical And Morphological Improvement Of Lupus Nephritis Treated With Rituximab.
AB - AIM: TO assess the effects of rituximab (RTM) therapy on clinical and morphologic
activity of lupus nephritis (LN). MATERIAL AND METHODS: The study included 45
patients with confirmed diagnosis of systemic lupus erythematosus (SLE),
unaffected by previously received standard therapy with glucocorticoids (GCs) and
cytostatics. The disease activity was assessed using Systemic Lupus Erythematosus
Disease Activity Index 2000 (SLEDAI 2K); to assess the LN activity we used the
SLICC RA/RE index. Forty-five patients with LN were given puncture renal biopsy
prior to prescribing RTM; 16 patients had repeated renal biopsy 1 year and more
after beginning the anti-B-cell therapy. LN was graded histologically in
accordance with the WHO classification (2003) with indices of activity (AI) and
chronicity (CI). RESULTS: The predominant number of patients had class III - IV
of LN. The repeated renal biopsies demonstrated that LN had undergone a
transition into a more favourable morphologic class, which was associated, in
most of these cases, with a positive therapeutic effect. The follow-up dynamics
showed a statistically significant reduction of AI (p=0.006), and no
statistically significant changes in the CI (p = 0.14). CONCLUSION: The long-term
follow-up in the study has showed that repeated courses of anti-B-cell therapy
with RTM have a positive effect both on SLE activity and generally on the renal
process. The reduction of the morphologic class of LN as assessed in the repeated
renal biopsies is a convincing proof for this. Eleven out of 16 patients
experienced transition of the morphologic class into a more favourable type,
which in most cases was combined with lower AI (p = 0.006). We found no evidence
of increase in the CI (p = 0.14).
PMID- 26444354
TI - Medical And Surgical Management Of Orbital Cellulitis In Children.
AB - OBJECTIVE: The purpose of this study was to identify features of orbital
cellulitis that predict response to conservative treatment without surgical
intervention and factors associated with a decision for surgery. PATIENTS AND
METHODS: The medical files of patients diagnosed with orbital cellulitis at a
tertiary medical center in central Israel between 1995 and 2010 were reviewed for
clinical data, diagnosis, complications, and type of treatment. Comparison was
made between patients treated with antibiotics and patients treated with
antibiotics and surgery. RESULTS: Fifty-one patients (35 male) with a mean age of
6.1 years were identified. Main clinical signs included fever (mean 38.5 degrees
C), proptosis (82.3%), extraocular motility restriction (74.5%), and ocular pain
(41.1%). Forty-one patients were successfully treated with antibiotics and 10
required endoscopic sinus surgery. On between-group comparison, the surgery group
had severe eye pain (p = 0.009), severe proptosis (P = 0.02), longer intravenous
antibiotic treatment (13.2 vs. 9.2 days, p = 0.04), and several imaging findings.
Additional factors associated with surgical intervention included older children,
subperiorbital abscess, larger dimension of the abscess (mean 15 mm), involvement
of frontal sinuses and findings of intraorbital air bubbles. There was no visual
deterioration in either group and no late sequelae. CONCLUSION: Factors
associated with surgery included age older than 9 years, severe ocular pain,
severe proptosis, and subperiorbital large abscess. These may be used for early
identification of patients at risk of failure of only medical management.
PMID- 26444356
TI - Behaviour Evaluation Scales For Pediatric Dental Patients - Review And Clinical
Experience.
AB - The present article makes a review of the relevant literature on the scales used
in the assessment of behaviour of pediatric dental patients as well as presents
the results we have had of using a modified Kurosu Behaviour Evaluation Scale to
assess a study sample. The review makes a critical analysis of current evaluation
methods and the design of assessment scales. The assessment tools most commonly
used in pediatric dentistry are presented in a chronological order from the past
to the present. The clinical study we conducted used a modified Behaviour
Evaluation Scale developed by Kurosu for the assessment of the behaviour of
children. The study showed that during dental treatment of children in the age
range of 6 to 12 years the prevailing objective behaviour characteristics in
accordance with Kurosu's behaviour evaluation scale are related to the eyes and
the facial expression. The findings from the literature review and the results of
our study warrant further studies to develop easy-to-use assessment tools that
would enhance the objective assessment of behaviour.
PMID- 26444355
TI - Surgical Site Infection In Orthopaedic Surgery: Correlation Between Age,
Diabetes, Smoke And Surgical Risk.
AB - INTRODUCTION: Surgical site infection is a common complication after orthopaedic
surgery. It can be associated with increased morbidity rate and social cost. The
accurate identification of risk factors is essential so that strategies to
prevent these potentially devastating infections can be developed. We have
conducted this study to determine the possible risk factors for the surgical site
infections. OBJECTIVES: We aimed at finding exhaustive evidence concerning the
potential risk factors for infections in orthopaedic surgery. PATIENTS AND
METHODS: Between October 2009 and December 2011, we identified 84 patients with a
superficial and/or deep surgical site infection and compared them with 203
uninfected patients (control group), taken out from a series of 486 patients. We
considered the following risk factors: diabetes, BMI >30, ASA Score of 3 or 4,
smoking and age. RESULTS: The most frequently performed operations of the 287
examined patients were the knee and hip arthroplasties (n = 32, 11.14%) and open
fracture reductions (n = 178, 62.02%). Staphylococcus Aureus was the most common
identified pathogen (n = 63, 75%). The analyses (preoperative and postoperative)
of the infected patients showed them to have significantly high serum glucose
levels in comparison with the control group (odds ratio = 8.7). We found a
significant high rate of infection in patients smoking for more than 20 years (67
patients, 79.7%). The remaining variables (BMI, OR = 2.21; ASA score, OR = 1.3)
showed no significant differences between the study group and controls. We also
found a correlation between > 65-year-old patients and infections at the surgical
site (61 patients, 72.6%). CONCLUSION: We found that there was correlation
between diabetes, smoking and age as risk factors with the development of
infection at the surgical site; other variables such as the ASA score and BMI are
not relevant here (contrary to what is reported in literature). We believe that
postoperative results can be improved considerably with a properly conducted
antibiotic treatment, stringent glycemic control (achievable only with careful
multidisciplinary management) and good compliance of patients.
PMID- 26444357
TI - Clear Cell Sarcoma Of Metatarsus.
AB - We report a case of clear cell sarcoma in the third metatarsus of the right foot.
This type of tumor is very rare and scantily reported in literature. A 42-year
old Caucasian male presented with a nodular ulcerated mass on the dorsal side of
the left foot. X-rays demonstrated a nodular solid lesion which dislodged the
third metatarsus. A biopsy revealed a neoplastic proliferation with a sarcoma
clear cell profile; because of the aggressive nature of this type of neoplasm, we
performed a trans-tibial amputation according to Bugess to achieve a better
functionality for the patient. The present study underlines clinical,
morphological, as well as imaging and therapeutic aspects of a rare neoplasm such
as clear cell sarcoma. The location site is also quite unusual - the metatarsus
of the foot. The histological and immunohistochemical data were suggestive of the
diagnosis of clear cell sarcoma of metatarsus. After MRI and a bone scan, the
surgical treatment suggested the extension over the forefoot and the ankle and
therefore a trans-tibial amputation was made.
PMID- 26444358
TI - Investigation Of Chromium-Cobalt Coated Scaffolds On Cell Cultures In Vitro.
AB - INTRODUCTION: The use of diverse materials for medical purposes is continuously
expanding. The modification of materials which are routinely applied in medical
practice as well as the development and introduction of new materials require
studies on their biological activity. The first steps in this process are the
preliminary short-term screening tests for cytotoxicity and biocompatibility
performed on cell cultures. METHODS: Coating of stainless steel (316 L) scaffolds
with chromium-cobalt was performed by electroplating using the non-standard
electrolyte Chromispel. The process was carried through at different cathode
current densities and deposition times. The modified surface of the metal
scaffolds was studied for cytoxicity and cell vitality on the serum-free McCoy
Plovdiv and the immortalized PDL cell cultures. RESULTS: Our results indicate no
cytotoxic effect of the coated metal scaffolds. Even more, three of the samples
stimulated the proliferation and growth of McCoy-Plovdiv cells. CONCLUSION: We
have strong reasons to believe that chromium-cobalt coatings are promising for
future studies and reliable for medical purposes.
PMID- 26444359
TI - Latent Bipolarity In Unipolar Depression: Experimental Findings, Conceptual
Analysis And Implications For Treatment Strategies.
AB - INTRODUCTION: Previous studies have suggested that the two opposite poles of
psychomotor disturbances in unipolar depression (UD) - retardation and agitation
require different treatment strategies as the psychomotor overactivation
requires an augmentation of the antidepressant therapy with mood stabilizers
and/or atypical antipsychotics. OBJECTIVE: The aim of the present study was to
objectively identify and measure the psycho-motor disturbances in UD using
differentiation between activity and reactivity. MATERIAL AND METHODS: An
equilibriometric movement pattern analysis system that allows differentiation
between psychomotor activity and reactivity was applied in 58 unipolar depressive
patients and 76 healthy controls. RESULTS: Compared to controls, the patients as
a group were significantly slower in their psychomotor reactivity. However, the
subsequent subgrouping according to the direction of deviation of their objective
psychomotor parameters revealed a disinhibition of psychomotor activity and/or
reactivity in about one half of them. Such a contradictory combination of
clinically manifested depressive mood and subclinically detected manic-like
psychomotor overactivation might be regarded as belonging to the bipolar
spectrum, since it was admitted that manic psychomotor disinhibition in unipolar
depressive patients uncovers a latent bipolarity. CONCLUSION: Not only
prototypical depressive inhibition, but also prototypical manic-like
disinhibition may underlie clinically manifested UD. Since the combination
between depressive mood and psychomotor overactivation multiplies the suicidal
risk, we may presume that the timely detection of this combination at a
subclinical level would contribute to an earlier and more effective suicidal
prevention by an objectively-guided optimization of pharmacological treatment.
PMID- 26444360
TI - Emergence Of Consciousness And Qualia From A Complex Brain.
AB - Qualia are private conscious experiences of which the associated feelings can be
reported to other people. Whether qualia are amenable to scientific exploration
has often been questioned, which is challenged by the present article. The
following arguments are given: 1. the configuration of the brain changes
continuously and irreversibly, because of genetic and environmental influences
and interhuman communication; 2. qualia and consciousness are processes, rather
than states; 3. private feelings, including those associated with qualia, should
be positioned in the context of a personal brain as being developed during life;
4. consciousness and qualia should be understood in the context of general system
theory, thus concluding that isolated, in vitro, properties of neurons and other
brain constituents might marginally contribute to the understanding of higher
brain functions, mind or qualia; 5. current in vivo approaches have too little
resolution power - in terms of space and time - to delineate individual and
subjective brain processes. When subtle personalized properties of the nervous
system can be assessed in vivo or in vitro, qualia can scientifically be
investigated. We discuss some approaches to overcome these barriers.
PMID- 26444361
TI - World, Time And Anxiety. Heidegger's Existential Analytic And Psychiatry.
AB - Martin Heidegger was one of the most influential but also criticized philosophers
of the XX century. With Being and Time 1927 he sets apart his existential
analytic from psychology as well as from anthropology and from the other human
sciences that deny the ontological foundation, overcoming the Cartesian dualism
in search of the ontological unit of an articulated multiplicity, as human being
is. Heidegger's Dasein Analytic defines the fundamental structures of human being
such as being-in-the-world, a unitary structure that discloses the worldhood of
the world; the modes of being (Seinsweisen), such as fear (Furcht) and anxiety
(Angst); and the relationship between existence and time. In his existential
analytic, anxiety is one of the fundamental moods (Grundbefindlichkeit) and it
plays a pivotal role in the relationship of Dasein with time and world. The paper
firstly focuses on the modes of being, underlining the importance of anxiety for
the constitution of human being; secondly, it shows the relationship between
anxiety and the world, and anxiety and time: rejecting both the Aristotelian
description of time, as a sequence of moments that informs our common
understanding of time, and the Augustine's mental account of inner time,
Heidegger considers temporality under a transcendental point of view. Temporality
is ek-static, it is a process through which human being comes toward and back to
itself, letting itself encounter the world and the entities. The transcendental
interpretation of time provided by Heidegger may give its important contribution
to psychopathology.
PMID- 26444362
TI - Mental Illness And Brain Disease.
AB - It has become common to say psychiatric illnesses are brain diseases. This
reflects a conception of the mental as being biologically based, though it is
also thought that thinking of psychiatric illness this way will reduce the stigma
attached to psychiatric illness. If psychiatric illnesses are brain diseases,
however, it is not clear why psychiatry should not collapse into neurology, and
some argue for this course. Others try to maintain a distinction by saying that
neurology deals with abnormalities of neural structure while psychiatry deals
with specific abnormalities of neural functioning. It is not clear that
neurologists would accept this division, nor that they should. I argue that if we
take seriously the notion that psychiatric illnesses are mental illnesses we can
draw a more defensible boundary between psychiatry and neurology. As mental
illnesses, psychiatric illnesses must have symptoms that affect our mental
capacities and that the sufferer is capable of being aware of, even if they are
not always self-consciously aware of them. Neurological illnesses, such as stroke
or multiple sclerosis, may be diagnosed even if they are silent, just as the
person may not be aware of having high blood pressure or may suffer a silent
myocardial infarction. It does not make sense to speak of panic disorder if the
person has never had a panic attack, however, or of bipolar disorder in the
absence of mood swings. This does not mean psychiatric illnesses are not
biologically based. Mental illnesses are illnesses of persons, whereas other
illnesses are illnesses of biological individuals.
PMID- 26444363
TI - Clinical examinations after the Fukushima disaster: a case report of Soma General
Hospital.
PMID- 26444364
TI - The side effects of translational omics: overtesting, overdiagnosis,
overtreatment.
AB - High-throughput technologies such as next-generation genomics, transcriptomics
and proteomics are capable of generating massive amounts of data quickly, and at
relatively low costs. It is tempting to use this data for various medical
applications including preclinical disease detection and for prediction of
disease predisposition. Pilot projects, initiated by various research groups and
Google, are currently underway, but results with not be available for a few
years. We here summarize some possible difficulties with these approaches, by
using examples from already tried cancer and other screening programs. Population
screening, especially with multiparametric algorithms, will identify at least
some false positive parameters and screening programs will identify abnormal
results in otherwise healthy individuals. Whole genome sequencing will identify
genetic changes of unknown significance and may not predict accurately future
disease predisposition if the disease is also influenced by environmental
factors. In screening programs, if the disease is rare, the positive predictive
value of the test will be low, even if the test has excellent sensitivity and
specificity. False positive results may require invasive procedures to delineate.
Furthermore, screening programs are not effective if the cancer grows quickly,
and will identify indolent forms of the disease with slow-growing tumors. It has
also been recently shown that for some cancers, more intensive and radical
treatments do not usually lead to better clinical outcomes. We conclude that new
omics testing technologies should avoid overdiagnosis and overtreatment and need
to be evaluated for overall clinical benefit before introduction to the clinic.
PMID- 26444365
TI - ABCG2/BCRP interaction with the sea grass Thalassia testudinum.
AB - BACKGROUND: The aqueous ethanolic extract from leaves of the marine plant
Thalassia testudinum has shown antioxidant, cytoprotective, and neuroprotective
properties. The chemical composition of this extract, rich in polyphenols, could
interfere with active transport of drugs out of the cell and circumvent the
phenomenon of multidrug resistance (MDR). The extract can act as an MDR modulator
through its interaction with efflux transporters. The ABCG2/BCRP has been shown
to confer MDR acting in tumor cells. METHODS: To evaluate the interaction of
ABCG2/BCRP with the extract, studies in cells overexpressing human BCRP
transporter and its murine ortholog Bcrp1 were performed. RESULTS AND
CONCLUSIONS: T. testudinum extract could be included as MDR modulator, as
interaction with ABCG2/BCRP has been shown through flow cytometry and MTT assays.
The cells overexpressing ABCG2/BCRP in the presence of the extract (25-150
MUg/mL) decreased the survival rates of the anti-tumoral mitoxantrone. Our
results support its inclusion as a possible MDR modulator against tumor cells
that overexpress ABCG2/BCRP.
PMID- 26444366
TI - Beauty.
PMID- 26444367
TI - Q&A: Karl Grammer. Innate attractions.
PMID- 26444368
TI - Masculinity: Men's makeover.
PMID- 26444369
TI - Mental health: Monsters in the mirror.
PMID- 26444370
TI - Q&A: David Deutsch. Objective beauty.
PMID- 26444371
TI - Beauty: 4 big questions.
PMID- 26444372
TI - Neuroscience: The aesthetic brain.
PMID- 26444373
TI - Cosmetics: Molecular beauty.
PMID- 26444374
TI - Surgery: Diverse interventions.
PMID- 26444375
TI - Animal behaviour: Come mate with me.
PMID- 26444376
TI - Delayed administration of recombinant human erythropoietin reduces apoptosis and
inflammation and promotes myelin repair and functional recovery following spinal
cord compressive injury in rats.
AB - PURPOSE: A previous study showed that a 1-h delay in treatment of thoracic spinal
cord injury (SCI) with recombinant human erythropoietin (rhEPO) lacked
neuroprotective efficacy. The aim of the present study was to reassess delayed
administration of different doses of rhEPO on acute spinal cord compressive
injury in rats. METHODS: The experiment was divided into first and second stages,
which SCI rats were observed for 4 and 28 days, respectively. All rats were
randomly divided into four groups at both stages: control group, and rhEPO-3,000U
(Unit), rhEPO-4,000U and rhEPO-5,000U groups. SCI rats received rhEPO treatment
at different time points. The primary indicators were locomotor recovery,
histopathology, apoptotic index, inflammatory index, ultrastructural scoring
system and volume of areas of demyelination. RESULTS: The most significant
locomotor functional and histopathological improvements and the best myelin
protection were observed after administration of 5,000 U/kg rhEPO. rhEPO at
3,000, 4,000 and 5,000 U/kg showed similar ultrastructural neuroprotection, as
well as similar inhibition of apoptosis and regulation of inflammation.
CONCLUSION: Delayed administration of rhEPO can reduce apoptosis and
inflammation, and promote myelin repair and functional recovery following spinal
cord compressive injury in rats.
PMID- 26444377
TI - CXCR4 antagonist AMD3100 reverses the neurogenesis and behavioral recovery
promoted by forced limb-use in stroke rats.
AB - PURPOSE: Forced limb-use can enhance neurogenesis and behavioral recovery as well
as increasing the level of stromal cell-derived factor-1 (SDF-1) in stroke rats.
We examined whether the SDF-1/CXCR4 pathway is involved in the enhanced
neurogenesis and promoted behavioral recovery induced by forced limb-use in the
chronic phase of stroke. METHODS: The CXCR4 antagonist, AMD3100, was used to
block the SDF-1/CXCR4 pathway in the ischemic rats. Brain ischemia was induced by
endothelin-1. One week after ischemia, the unimpaired forelimb of rats was
immobilized for 3 weeks. The proliferation, migration, and survival of DCX
positive cells in the subventricular zone (SVZ), and the dendritic complexity of
DCX-positive cells in the dentate gyrus (DG), as well as the inflammatory
response in the infarcted striatum were analyzed by immunohistochemistry.
Functional recovery was assessed in beam-walking and water maze tests. RESULTS:
Forced limb-use enhanced the proliferation, migration, dendritic complexity and
the survival of newborn neurons. Furthermore, forced limb-use suppressed the
inflammatory response and improved both motor and cognitive functions after
stroke. AMD3100 significantly abrogated the enhanced neurogenesis and behavioral
recovery induced by forced limb-use without influencing the inflammatory
response. CONCLUSIONS: SDF-1/CXCR4 pathway seems to be involved in the
enhancement of neurogenesis and behavioral recovery induced by post-stroke forced
limb-use.
PMID- 26444378
TI - Determination of Neutral Monosaccharides as Per-O-methylated Derivatives Directly
from a Drop of Whole Blood by Gas Chromatography-Mass Spectrometry.
AB - A new analytical procedure was developed for the simultaneous quantification of
neutral monosaccharides from a drop of whole blood using gas chromatography-mass
spectrometry analysis (GC-MS) of their per-O-methylated derivatives. The per-O
methylation reaction with methyl iodide and solid sodium hydroxide in methyl
sulfoxide was used for the first time for analysis of blood monosaccharides. A
blood drop volume of 0.6 MUL was used without special purification. The
elimination of the undesirable components was carried out during methylation in
the presence of a strong base and by liquid extraction of the per-O-methylated
monosaccharides. The neutral monosaccharides with an anomeric center gave four
per-O-methylated isomers, which were well-separated using a capillary column.
Identification was done by electron impact mass spectrometry fragmentation,
retention times, and library searching. The limits of detection were determined
for standards and varied from 2.0 to 2.3 ng mL(-1). Recoveries for human blood
samples varied from 99.22% to 99.65%. The RSD values ranged from 1.92 to 2.37.
The method is fast, sensitive, reproducible, and an alternative to current
methods for quantitative analysis of blood monosaccharides.
PMID- 26444379
TI - Synthesis and Antiproliferative Activity Evaluation of the Disulfide-Containing
Cyclic Peptide Thiochondrilline C and Derivatives.
AB - Thiochondrilline C (4) was previously isolated from Verrucisispora sp. and
reported to have moderate cytotoxicity against human lung adenocarcinoma cells.
Herein, we report the synthesis of thiochondrilline C by N-terminal peptide
extension, oxidative disulfide bond formation, and heterocycle installation as
key steps. Antiproliferative activities for the prepared natural product and
several derivatives against the NCI 60 cancer cell line panel are also described.
Derivative 22 was identified as a moderately potent antiproliferative agent (50%
growth inhibition (GI50) = 0.2-12.2 MUM) with leukemia (average GI50 = 1.8 +/-
0.1 MUM) and colon (average GI50 = 2.4 +/- 0.3 MUM) cells being most sensitive.
PMID- 26444380
TI - Accounting for Diradical Character through DFT. The Case of Vinyl Allene Oxide
Rearrangement.
AB - The transformation of vinyl allene oxides into cyclopentenones is key to the
biosynthesis of a number of hormone-like molecules in plants. Two competitive
paths are generally accepted for this transformation: a concerted SN2-like
mechanism and a stepwise path with a diradical oxyallyl intermediate. Recently, a
new stepwise closed-shell path has been proposed that circumvents the key
oxyallyl intermediate. In this work, we conduct a thorough computational
investigation, including dynamic effects, to identify the most likely mechanism
for this transformation.
PMID- 26444381
TI - Molecular Heterogeneity of Thalassemia among Pregnant Laotian Women.
AB - BACKGROUND AND AIMS: A pilot screening program for thalassemia was initiated in
the Lao People's Democratic Republic. This study aimed to describe the genotype
diversity and hematologic features of thalassemia among the participating
pregnant women. METHODS: Blood samples of 411 pregnant Laotian women were
collected. Hemoglobin (Hb) profiles were determined using a capillary zone
electrophoresis system. Mutations of alpha- and beta-globin genes were
investigated using a polymerase chain reaction and related techniques. RESULTS:
As many as 26 different thalassemia genotypes including non-transfusion-dependent
thalassemia, i.e. Hb E-beta-thalassemia, Hb H, and EA Bart's diseases, were
identified. A variety of phenotypic expressions of hematologic features and Hb
profiles were observed, including an unusual phenotype of Hb E-beta0 thalassemia
with 89.1% Hb E, 1.6% Hb F, and 9.3% Hb A2. CONCLUSIONS: The remarkable genotype
phenotype diversity indicates a need for careful laboratory interpretation in
order to provide appropriate genetic counseling and care to the Laotian
population.
PMID- 26444382
TI - Weight Loss Expectations and Attrition in Treatment-Seeking Obese Women.
AB - OBJECTIVE: The analysis of the relation between weight loss goals and attrition
in the treatment of obesity has produced conflicting results. The aim of the
present study was to investigate the role of weight loss goals on attrition in a
cohort of obese women seeking treatment at 8 Italian medical centres. METHODS:
634 women with obesity, consecutively enrolled in weight loss programmes, were
included in the study. Weight loss goals were evaluated with the Goals and
Relative Weights Questionnaire (GRWQ), reporting a sequence of unrealistic
('dream' and 'happy') and more realistic ('acceptable' and 'disappointing')
weight loss goals. Attrition was assessed at 12 months on the basis of patients'
medical records. RESULTS: At 12 months, 205/634 patients (32.3%) had interrupted
their programme and were lost to follow-up. After adjustment for age, baseline
weight, education and employment status, attrition was significantly associated
with higher percent acceptable and disappointing weight loss targets, not with
dream and happy weight loss. CONCLUSION: In 'real world' clinical settings, only
realistic expectations might favour attrition whenever too challenging, whereas
unrealistic weight loss goals have no effect. Future studies should assess the
effect of interventions aimed at coping with too challenging weight goals on
attrition.
PMID- 26444383
TI - Role of Quantum Vibrations on the Structural, Electronic, and Optical Properties
of 9-Methylguanine.
AB - In this work, we report theoretical predictions of the UV-absorption spectra of 9
methylguanine using time dependent density functional theory (TDDFT). Molecular
dynamics simulations of the hydrated DNA base are peformed using an empirical
force field, Born-Oppenheimer ab initio molecular dynamics (AIMD), and finally
path-integral AIMD to understand the role of the underlying electronic potential,
solvation, and nuclear quantum vibrations on the absorption spectra. It is shown
that the conformational distributions, including hydrogen bonding interactions,
are perturbed by the inclusion of nuclear quantum effects, leading to significant
changes in the total charge and dipole fluctuations of the DNA base. The
calculated absorption spectra using the different sampling protocols shows that
the inclusion of nuclear quantum effects causes a significant broadening and red
shift of the spectra bringing it into closer agreement with experiments.
PMID- 26444384
TI - Deoxynyboquinones as NQO1-Activated Cancer Therapeutics.
AB - One of the major goals of cancer therapy is the selective targeting of cancer
cells over normal cells. Unfortunately, even with recent advances, the majority
of chemotherapeutics still indiscriminately kill all rapidly dividing cells.
Although these drugs are effective in certain settings, their inability to
specifically target cancer results in significant dose-limiting toxicities. One
way to avoid such toxicities is to target an aspect of the cancer cell that is
not shared by normal cells. A potential cancer-specific target is the enzyme
NAD(P)H quinone oxidoreductase 1 (NQO1). NQO1 is a 2-electron reductase
responsible for the detoxification of quinones. Its expression is typically quite
low in normal tissue, but it has been found to be greatly overexpressed in many
types of solid tumors, including lung, breast, pancreatic, and colon cancers.
This overexpression is thought to be in response to the higher oxidative stress
of the cancer cell, and it is possible that NQO1 contributes to tumor
progression. The overexpression of NQO1 and its correlation with poor patient
outcome make it an intriguing target. Although some have explored inhibiting NQO1
as an anticancer strategy, this has generally been unsuccessful. A more promising
strategy is to utilize NQO1 substrates that are activated upon reduction by NQO1.
For example, in principle, reduction of a quinone can result in a hydroquinone
that is a DNA alkylator, protein inhibitor, or reduction-oxidation cycler.
Although there are many proposed NQO1 substrates, head-to-head assays reveal only
two classes of compounds that convincingly induce cancer cell death through NQO1
mediated activation. In this Account, we describe the discovery and development
of one of these compounds, the natural product deoxynyboquinone (DNQ), an
excellent NQO1 substrate and anticancer agent. A modular synthesis of DNQ was
developed that enabled access to the large compound quantities needed to conduct
extensive mechanistic evaluations and animal experiments. During these
evaluations, we found that DNQ is an outstanding NQO1 substrate that is processed
much more efficiently than other putative NQO1 substrates. Importantly, its
anticancer activity is strictly dependent on the overexpression of active NQO1.
Using previous crystal structures of NQO1, novel DNQ derivatives were designed
that are also excellent NQO1 substrates and possess properties that make them
more attractive than the parent natural product for translational development.
Given their selectivity, potency, outstanding pharmacokinetic properties, and the
ready availability of diagnostics to assess NQO1 in patients, DNQ and its
derivatives have considerable potential as personalized medicines for the
treatment of cancer.
PMID- 26444385
TI - Designing of Biodegradable and Biocompatible Release and Delivery Systems of
Selected Antioxidants Used in Cosmetology.
AB - Conjugates of antioxidants p-anisic (p-AA) and vanillic (VA) acids with nontoxic,
biocompatible, and biodegradedable oligo-(R,S)-(3-hydoxybutyrate) carrier were
synthesized, and their structural and biological characterization was performed.
The molecular structure of the bioconjugates, in which antioxidants are
covalently bonded with oligo(3-hydroxybutyrate) (OHB) chains, has been proven by
mass spectrometry supported by NMR. The bioconjugate hydrolytic degradation
studies allowed gaining thorough insight into the hydrolysis process and
confirmed the release of p-AA and VA. In vitro studies demonstrated that all of
the conjugates studied were well tolerated by KB and HaCaT cell lines, as they
had no marked cytotoxicity, while conjugates with a relatively short OHB carrier
are optimal to support keratinocyte function. The preliminary study of the
biological activity confirmed the protective effect of VA-OHB conjugates against
H2O2-induced lipid peroxidation in human keratinocytes (HaCaT). It was also
demonstrated that the selected bioconjugates can penetrate all layers of the
skin, which shows their functionality and opens up their potential application in
cosmetology.
PMID- 26444386
TI - Predicting Honeybee Colony Failure: Using the BEEHAVE Model to Simulate Colony
Responses to Pesticides.
AB - To simulate effects of pesticides on different honeybee (Apis mellifera L.) life
stages, we used the BEEHAVE model to explore how increased mortalities of larvae,
in-hive workers, and foragers, as well as reduced egg-laying rate, could impact
colony dynamics over multiple years. Stresses were applied for 30 days, both as
multiples of the modeled control mortality and as set percentage daily
mortalities to assess the sensitivity of the modeled colony both to small
fluctuations in mortality and periods of low to very high daily mortality. These
stresses simulate stylized exposure of the different life stages to nectar and
pollen contaminated with pesticide for 30 days. Increasing adult bee mortality
had a much greater impact on colony survival than mortality of bee larvae or
reduction in egg laying rate. Importantly, the seasonal timing of the imposed
mortality affected the magnitude of the impact at colony level. In line with the
LD50, we propose a new index of "lethal imposed stress": the LIS50 which
indicates the level of stress on individuals that results in 50% colony
mortality. This (or any LISx) is a comparative index for exploring the effects of
different stressors at colony level in model simulations. While colony failure is
not an acceptable protection goal, this index could be used to inform the setting
of future regulatory protection goals.
PMID- 26444387
TI - Atopic Diseases and Subsequent Ischemic Stroke Among Patients With Schizophrenia:
A Nationwide Longitudinal Study.
AB - BACKGROUND: Chronic inflammation plays an important role in schizophrenia and
atopic diseases, and studies have suggested that chronic inflammation is
associated with an increased risk of stroke. The role of atopic diseases in the
development of stroke among patients with schizophrenia is still unknown.
METHODS: A total of 63,913 patients with schizophrenia without a stroke history
between 2002 and 2008 and 63,913 age- and sex-matched controls were included and
followed up to the end of 2011. Patients with schizophrenia and the reference
group were divided into subgroups based on the presence or absence of atopic
diseases. Individuals who developed stroke during follow-up were identified.
RESULTS: Patients with schizophrenia had an increased risk of developing ischemic
stroke (no atopic disease: hazard ratio [HR] = 2.18, 95% confidence interval [CI]
= 1.88-2.53; with atopic disease: HR = 3.11, 95% CI = 2.63-3.69) compared with
the reference group without atopic diseases. Among patients with schizophrenia,
the presence of atopic diseases increased the risk of developing ischemic stroke
(HR = 1.44, 95% CI = 1.24-1.66), with a cumulative relationship between greater
numbers of atopic comorbidities and a greater risk of ischemic stroke (one atopic
disease: HR = 1.39, 95% CI = 1.19-1.63; two atopic comorbidities: HR = 1.48, 95%
CI = 1.10-2.00; at least 3 atopic comorbidities: HR = 2.81, 95% CI = 1.55-5.12).
CONCLUSIONS: The combined presence of schizophrenia and atopic diseases is
associated with an increased risk of ischemic stroke in later life compared with
individuals without these conditions.
PMID- 26444388
TI - Dissociating biases towards the self and positive emotion.
AB - We examined whether self-biases in perceptual matching reflect the positive
valence of self-related stimuli. Participants associated geometric shapes with
either personal labels (e.g., you, friend, stranger) or faces with different
emotional expressions (e.g., happy, neutral, sad). They then judged whether shape
label or shape-face pairs were as originally shown or re-paired. Match times were
faster to self-associated stimuli and to stimuli associated with the most
positive valence. In addition, both the self-bias and the positive emotion bias
were reliable across individuals in different test sessions. In contrast there
was no sign of a correlation between the self-bias and the emotion-bias effects.
We argue that self-bias and the bias to stimuli linked to positive emotion are
separate and may reflect different underlying processes.
PMID- 26444390
TI - Sexual risk behaviors among apps-using young men who have sex with men in Hong
Kong.
AB - This study is among the first to examine the sexual risk behaviors and attendant
factors of young men who have sex with men (YMSM) in Hong Kong using location
aware gay social networking mobile applications ("gay apps"). Among the 213 YMSM
(Mage = 21.52, SD = 2.29 years, range 17-25) who reported their recent (past six
months) sexual history with male partners and gay apps use, inconsistent condom
use (ICU) during anal sex was fairly common (60.2% regular partners, 45.8% non
regular partners). One-fifth of the sample reported condomless internal
ejaculation (CIE) during anal sex (19.3% insertive, 19.8% receptive). Frequent
"Grindr" and "Jack'd" users were less likely to report anal sex, and hence ICU,
with regular [adjusted odds ratio (AOR) = 0.72] and non-regular (AOR = 0.62)
partners, respectively. Sexual partnering via apps doubled the odds of ICU with
both regular (AOR = 1.99) and non-regular (AOR = 2.17) partners. The odds of ICU
with regular partners also increased with relationship status (AOR = 2.86
exclusive, AOR = 3.23 non-exclusive) but reduced for those who never had STI/HIV
testing (AOR = 0.27). With non-regular partners, YMSM's likelihood of ICU
increased with more recent partners (AOR = 3.25) and drug use (AOR = 3.79), but
reduced with group sex (AOR = 0.15). The odds of receptive CIE increased with
alcohol consumption (AOR = 4.04), non-exclusive relationship (AOR = 4.10), and
more recent partners (AOR = 2.47), but reduced with group sex (AOR = 0.15) and
older age (AOR = 0.84). For insertive CIE, the odds increased with bisexual YMSM
(AOR = 2.89), exclusive relationship (AOR = 3.97), and longtime apps-use (AOR =
1.81). The findings identify meaningful differences among YMSM app-users that
inform sexual health intervention and suggest attention on alcohol or drug use
during sex and condomless sex with non-exclusive regular partners.
PMID- 26444391
TI - Beau B. Bruce, MD, PhD.
PMID- 26444389
TI - In vitro analyses of mitochondrial ATP/phosphate carriers from Arabidopsis
thaliana revealed unexpected Ca(2+)-effects.
AB - BACKGROUND: Adenine nucleotide/phosphate carriers (APCs) from mammals and yeast
are commonly known to adapt the mitochondrial adenine nucleotide pool in
accordance to cellular demands. They catalyze adenine nucleotide--particularly
ATP-Mg--and phosphate exchange and their activity is regulated by calcium. Our
current knowledge about corresponding proteins from plants is comparably limited.
Recently, the three putative APCs from Arabidopsis thaliana were shown to restore
the specific growth phenotype of APC yeast loss-of-function mutants and to
interact with calcium via their N-terminal EF--hand motifs in vitro. In this
study, we performed biochemical characterization of all three APC isoforms from
A. thaliana to gain further insights into their functional properties. RESULTS:
Recombinant plant APCs were functionally reconstituted into liposomes and their
biochemical characteristics were determined by transport measurements using
radiolabeled substrates. All three plant APCs were capable of ATP, ADP and
phosphate exchange, however, high preference for ATP-Mg, as shown for orthologous
carriers, was not detectable. By contrast, the obtained data suggest that in the
liposomal system the plant APCs rather favor ATP-Ca as substrate. Moreover,
investigation of a representative mutant APC protein revealed that the observed
calcium effects on ATP transport did not primarily/essentially involve Ca(2+)
binding to the EF-hand motifs in the N-terminal domain of the carrier.
CONCLUSION: Biochemical characteristics suggest that plant APCs can mediate net
transport of adenine nucleotides and hence, like their pendants from animals and
yeast, might be involved in the alteration of the mitochondrial adenine
nucleotide pool. Although, ATP-Ca was identified as an apparent import substrate
of plant APCs in vitro it is arguable whether ATP-Ca formation and thus the
corresponding transport can take place in vivo.
PMID- 26444392
TI - What's Hot in Neuro-Ophthalmology.
PMID- 26444393
TI - Ocular Fundus Photography as a Tool to Study Stroke and Dementia.
AB - Although cerebral small vessel disease has been linked to stroke and dementia,
due to limitations of current neuroimaging technology, direct in vivo
visualization of changes in the cerebral small vessels (e.g., cerebral arteriolar
narrowing, tortuous microvessels, blood-brain barrier damage, capillary
microaneurysms) is difficult to achieve. As the retina and the brain share
similar embryological origin, anatomical features, and physiologic properties
with the cerebral small vessels, the retinal vessels offer a unique and easily
accessible "window" to study the correlates and consequences of cerebral small
vessel diseases in vivo. The retinal microvasculature can be visualized,
quantified and monitored noninvasively using ocular fundus photography. Recent
clinic- and population-based studies have demonstrated a close link between
retinal vascular changes seen on fundus photography and stroke and dementia,
suggesting that ocular fundus photography may provide insights to the
contribution of microvascular disease to stroke and dementia. In this review, we
summarize current knowledge on retinal vascular changes, such as retinopathy and
changes in retinal vascular measures with stroke and dementia as well as
subclinical makers of cerebral small vessel disease, and discuss the possible
clinical implications of these findings in neurology. Studying pathologic changes
of retinal blood vessels may be useful for understanding the etiology of various
cerebrovascular conditions; hence, ocular fundus photography can be potentially
translated into clinical practice.
PMID- 26444394
TI - Nonmydriatic Ocular Fundus Photography in the Emergency Department: How It Can
Benefit Neurologists.
AB - Examination of the ocular fundus is a critical aspect of the neurologic
examination. For example, in patients with headache the ocular fundus examination
is needed to uncover "red flags" suggestive of secondary etiologies. However,
ocular fundus examination is infrequently and poorly performed in clinical
practice. Nonmydriatic ocular fundus photography provides an alternative to
direct ophthalmoscopy that has been studied as part of the Fundus Photography
versus Ophthalmoscopy Trial Outcomes in the Emergency Department (FOTO-ED) Study.
Herein, the results of the FOTO-ED study are reviewed with a particular focus on
the study's implications for the acute care of patients presenting with headache
and focal neurologic deficits. In headache patients, not only optic disc edema
and optic disc pallor were observed as would be expected, but also a large number
of abnormalities associated with hypertension. Based upon subjects with focal
neurologic deficits, the FOTO-ED study suggests that the ocular fundus
examination may assist with the triage of patients presenting with suspected
transient ischemic attack. Continued advances in the ease and portability of
nonmydriatic fundus photography will hopefully help to restore ocular fundus
examination as a routinely performed component of all neurologic examinations.
PMID- 26444395
TI - Ocular Fundus Photography as an Educational Tool.
AB - The proficiency of nonophthalmologists with direct ophthalmoscopy is poor, which
has prompted a search for alternative technologies to examine the ocular fundus.
Although ocular fundus photography has existed for decades, its use has been
traditionally restricted to ophthalmology clinical care settings and textbooks.
Recent research has shown a role for nonmydriatic fundus photography in
nonophthalmic settings, encouraging more widespread adoption of fundus
photography technology. Recent studies have also affirmed the role of fundus
photography as an adjunct or alternative to direct ophthalmoscopy in
undergraduate medical education. In this review, the authors examine the use of
ocular fundus photography as an educational tool and suggest future applications
for this important technology. Novel applications of fundus photography as an
educational tool have the potential to resurrect the dying art of funduscopy.
PMID- 26444396
TI - Diagnosing Stroke in Acute Vertigo: The HINTS Family of Eye Movement Tests and
the Future of the "Eye ECG".
AB - Patients who present to the emergency department with symptoms of acute vertigo
or dizziness are frequently misdiagnosed. Missed opportunities to promptly treat
dangerous strokes can result in poor clinical outcomes. Inappropriate testing and
incorrect treatments for those with benign peripheral vestibular disorders leads
to patient harm and unnecessary costs. Over the past decade, novel bedside
approaches to diagnose patients with the acute vestibular syndrome have been
developed and refined. A battery of three bedside tests of ocular motor
physiology known as "HINTS" (head impulse, nystagmus, test of skew) has been
shown to identify acute strokes more accurately than even magnetic resonance
imaging with diffusion-weighted imaging (MRI-DWI) when applied in the early acute
period by eye-movement specialists. Recent advances in lightweight, high-speed
video-oculography (VOG) technology have made possible a future in which HINTS
might be applied by nonspecialists in frontline care settings using portable VOG.
Use of technology to measure eye movements (VOG-HINTS) to diagnose stroke in the
acute vestibular syndrome is analogous to the use of electrocardiography (ECG) to
diagnose myocardial infarction in acute chest pain. This "eye ECG" approach could
transform care for patients with acute vertigo and dizziness around the world. In
the United States alone, successful implementation would likely result in
improved quality of emergency care for hundreds of thousands of peripheral
vestibular patients and tens of thousands of stroke patients, as well as an
estimated national health care savings of roughly $1 billion per year. In this
article, the authors review the origins of the HINTS approach, empiric evidence
and pathophysiologic principles supporting its use, and possible uses for the eye
ECG in teleconsultation, teaching, and triage.
PMID- 26444397
TI - Treatment of Nystagmus.
AB - Acquired and congenital forms of nystagmus are commonly encountered in the course
of clinical practice. Although some patients are asymptomatic, many others
describe disabling oscillopsia that impairs visual function, social function, and
quality of life. Such patients may present to the neurologist to request
treatment. Numerous treatment approaches for nystagmus have been proposed,
including medical, surgical, and optical treatments. Some of the treatments aim
to reduce nystagmus slow-phase speed, whereas others aim to negate the visual
consequences of the nystagmus. The approach must be tailored depending on the
type of nystagmus, its characteristics, and in some cases, its cause. In this
review, the treatment approach for acquired and congenital forms of nystagmus is
summarized with an emphasis on treatments that have been evaluated in well
designed clinical trials. Novel approaches that have not yet been evaluated in
clinical trials are also discussed.
PMID- 26444398
TI - Update on the Diagnosis and Treatment of Idiopathic Intracranial Hypertension.
AB - Idiopathic intracranial hypertension (IIH) is a rare disorder occurring more
frequently in obese women of childbearing age, resulting in increased
intracranial pressure (ICP) from an unknown cause. Recent advances in
epidemiology, imaging, and treatment have provided a better understanding of IIH
in recent years, with better identification of visual risk factors and atypical
forms of IIH, including fulminant IIH and spontaneous cerebrospinal fluid leaks,
and a randomized clinical trial providing the rationale for the use of
acetazolamide. In addition, a revised version of the modified Dandy criteria for
the diagnosis of IIH was suggested in 2013, with better definition of IIH in
adults and children; however, controversy regarding nomenclature has precluded
its acceptance among IIH experts. Finally, questions regarding the best surgical
strategy, the indications for venous sinus stenting, and the diagnostic role of
the radiologic findings commonly seen in IIH have remained unanswered.
PMID- 26444399
TI - Isolated Ocular Motor Nerve Palsies.
AB - An isolated ocular motor nerve palsy is defined as dysfunction of a single ocular
motor nerve (oculomotor, trochlear, or abducens) with no associated or localizing
neurologic signs or symptoms. When occurring in patients aged 50 or older, the
most common cause is microvascular ischemia, but serious etiologies such as
aneurysm, malignancy, and giant cell arteritis should always be considered. In
this article, the authors review the clinical approach, anatomy, and differential
diagnosis of each isolated ocular motor nerve palsy and discuss the clinical
characteristics, pathophysiology, and treatment of microvascular ischemia.
PMID- 26444400
TI - Prognosis and Treatment of Visual Field Defects.
AB - Visual field deficits are common in neurologic disease conditions such as
cerebrovascular disease, traumatic brain injury, and brain tumors. Loss of visual
fields may lead to impairment of reading skills (hemianopic dyslexia) and
limitations of daily activities such as driving, which can have a significant
impact on an individual's socioeconomic status and quality of life. Moreover,
patients with motor deficits from neurologic diseases have a 20% decreased
likelihood of achieving independence in ambulation and self-care activities with
coexisting hemianopia. Studies on the natural history of homonymous hemianopia
have shown that spontaneous improvement of visual fields may occur in less than
40% of individuals early in the disease process. Improvement is usually
incomplete, which implies that a significant number of individuals will be left
with a disabling visual deficit. Although several methods of rehabilitation
(optical, compensatory, and restitution therapy) are used in practice, none,
unfortunately, have shown consistent and significant benefits. In this review,
the authors focus on the natural history, impact, prognosis, and treatment
modalities for neurologic field defects.
PMID- 26444401
TI - Functional Vision Disorder.
AB - Functional vision disorder (FVD) is a common problem seen in many neurologic and
ophthalmologic practitioners' offices and may occur in isolation or in the
presence of medical illness. This disorder presents with visual or oculomotor
symptoms and manifests as vision loss in one or both eyes, visual field loss,
double vision, oscillopsia, anisocoria, blepharospasm, or ptosis. Manual
perimetry is the most effective method for determining functional visual loss,
and the presence of a central scotoma in a functional visual field signifies that
a neuropathophysiologic process is almost certainly present. The exact
neuropathophysiologic mechanism of this disorder is unknown; however, information
can be drawn from the small studies of FVD samples and studies examining
neuropsychiatric factors in other conversion disorder semiologies. Psychological
and psychiatric interventions can be useful in treating these patients.
PMID- 26444402
TI - Optical Coherence Tomography for the Neurologist.
AB - Optical coherence tomography (OCT) is a relatively new technology that is now
routinely and very widely used by ophthalmologists for structural documentation
of the optic nerve and retina. In neuro-ophthalmology and neurology, the value of
OCT is ever expanding; its role in an increasing number of conditions is being
reported in parallel with the advances of the technology. Currently, as a
clinical tool, OCT is particularly useful for the structural measurement of
peripapillary retinal nerve fiber layer thickness, optic nerve head volumetric
analysis, and macular anatomy. Optic neuropathies of varied etiology
(particularly from multiple sclerosis) may be the most common clinical
indications for neurologists to obtain OCT imaging. Documentation and follow-up
of disc edema of varied etiology (papilledema and idiopathic intracranial
hypertension), discriminating true disc swelling from pseudopapilledema, and
differentiating optic neuropathy from maculopathy are some other examples from
clinical practice.
PMID- 26444403
TI - Therapeutic Approaches to Inherited Optic Neuropathies.
AB - As a group, inherited optic neuropathies represent an important cause of severe
irreversible visual loss among children and young adults. Leber hereditary optic
neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most
common forms encountered in clinical practice and several shared disease pathways
have emerged that contribute to retinal ganglion cell loss, and eventually visual
failure. In this review, the author critically appraises the evidence base for
the various therapeutic strategies that have been put forward to treat these two
mitochondrially determined optic neuropathies, including future developments.
Innovative in vitro fertilization techniques to prevent female carriers of
childbearing age from transmitting pathogenic mitochondrial DNA mutations to
their biological children will also be discussed.
PMID- 26444404
TI - The Effects of Primary Brain Tumors on Vision and Quality of Life in Pediatric
Patients.
AB - Brain tumors are the leading cause of death from childhood cancer. Overall
survival has improved due to earlier detection, better therapies, and improved
posttreatment surveillance. Permanent sequelae of the tumor and its treatment may
cause severe impairment and decreased quality of life (QoL). Pediatric primary
brain tumor patients' vision can be severely affected, even when the tumor
location does not primarily involve the visual pathway. Visual dysfunction and
impaired vision-related QoL may not be detected or screened for in children with
primary brain tumors for many reasons, including examination difficulty and lack
of awareness. The authors review the ophthalmic presenting symptoms, effects on
vision, and quality of life in pediatric patients with primary brain tumors. They
also describe and emphasize the importance of systematic neuro-ophthalmologic
examinations in this population, which may improve long-term visual and QoL
outcomes through earlier interventions.
PMID- 26444405
TI - The Concussion Toolbox: The Role of Vision in the Assessment of Concussion.
AB - Concussion may lead to subtle changes in brain function, and tests involving the
visual system probe higher cortical functioning and increase our sensitivity in
detecting these changes. Concussions are acutely and sometimes more persistently
associated with abnormalities in balance, cognition, and vision. The visual
system involves roughly half of the brain's circuits, including many regions
susceptible to head impacts. After a concussion, the neuro-ophthalmologic exam
commonly detects abnormalities in convergence, accommodation, the vestibulo
ocular reflex, ocular muscle balance, saccades, and pursuit. The King-Devick (K
D) test is a visual performance measure that may increase the sensitivity of
detecting concussions on the sideline when used in combination with tests of
cognition and balance that are part of the Sports Concussion Assessment Tool (3rd
ed.; SCAT3). Portable eye movement trackers and pupillometry may in the future
improve our neuro-ophthalmic assessment after concussions. Combining visual tasks
with neuroimaging and neurophysiology has allowed subtle changes to be detected,
may refine our ability to make appropriate return-to-play decisions, and could
potentially determine susceptibility to long-term sequelae of concussion.
PMID- 26444406
TI - Emergency team calls for critically ill non-trauma patients in the emergency
department: an observational study.
AB - BACKGROUND: Handling critically ill patients is a complex task for Emergency
Department (ED) personnel. Initial treatment is of major importance and requires
adequately experienced ED doctors to initiate and decide for the right medical or
surgical treatment. Our aim was, with regard to clinical presentation, management
and mortality to describe adult non-trauma patients that upon ED arrival elicited
emergency team calls. METHODS: An observational study of adult patients (>= 18
years) admitted to a regional ED with conditions that elicited acute team
activation and additional emergency team consultation calls for non-ED specialist
physicians. Emergency team calls were two-tiered with 'orange' and 'red' calls.
Additionally, intensive care unit (ICU) admission charts were reviewed to
identify the total number of adult non-trauma and non-cardiac arrest patients
admitted to the ICU from the ED during the study period. RESULTS: A total of 109
emergency team calls were triggered (79 orange and 30 red), comprising 66 (60.6
%) men and 43 women, with a median age of 64 years. Patients presented with: 4
Airway, 27 Breathing, 41 Circulation, 31 Disability, 2 Exposure and 4 Other
problems. Overall, 58/109 (53.2 %) patients were admitted to the ICU, while
20/109 (18.3 %) patients were deemed ineligible for ICU admission. 30-day
mortality was 34/109 (31.2 %), and circulatory problems were the most frequent
cause of death (61.8 %, p = 0.02). Patients who died were significantly older
than those who survived (p = 0.004). Additionally, 115 adult patients were
admitted to the ICU directly from the ED without eliciting an emergency team call
during the study period. These patients mainly comprised patients who were
intoxicated, were unconscious or had respiratory failure. CONCLUSION: The
majority of emergency team call patients presented with circulatory, disability
and breathing problems. Half of the patients were admitted to the ICU, although a
high rate of patients was deemed ineligible for ICU admission. 30-day mortality
was considerable and circulatory related illnesses were associated with increased
short-term mortality.
PMID- 26444408
TI - ?
PMID- 26444407
TI - Air toxics and the risk of autism spectrum disorder: the results of a population
based case-control study in southwestern Pennsylvania.
AB - BACKGROUND: Autism spectrum disorders (ASD) constitute a major public health
problem affecting one in 68 children. There is little understanding of the causes
of ASD despite its serious social impact. Air pollution contains many toxicants
known to have adverse effects on the fetus. We conducted a population based case
control study in southwestern Pennsylvania to estimate the association between
ASD and 2005 US EPA modeled NATA (National Air Toxics Assessment) levels for 30
neurotoxicants. METHODS: A total of 217 ASD cases born between 2005 and 2009 were
recruited from local ASD diagnostic and treatment centers. There were two
different control groups: 1) interviewed controls (N = 224) frequency matched by
child's year of birth, sex and race with complete residential histories from
prior to pregnancy through the child's second birthday, and 2) 5,007 controls
generated from a random sample of birth certificates (BC controls) using
residence at birth. We used logistic regression analysis comparing higher to
first quartile of exposure to estimate odds ratios (ORs) and 95% confidence
intervals (CI), adjusting for mother's age, education, race, smoking status,
child's year of birth and sex. RESULTS: Comparing fourth to first quartile
exposures for all births, the adjusted OR for styrene was 2.04 (95% CI = 1.17
3.58, p = 0.013) for the interviewed case-control analysis and 1.61 (95% CI =
1.08-2.40, p = 0.018) for the BC analysis. In the BC comparison, chromium also
exhibited an elevated OR of 1.60 (95% CI = 1.08-2.38, p = 0.020), which was
similarly elevated in the interviewed analysis (OR = 1.52, 95% CI = 0.87-2.66).
There were borderline significant ORs for the BC comparison for methylene
chloride (OR = 1.41, 95% CI = 0.96-2.07, p = 0.082) and PAHs (OR = 1.44, 95% CI =
0.98-2.11, p = 0.064). CONCLUSIONS: Living in areas with higher levels of styrene
and chromium during pregnancy was associated with increased risk of ASD, with
borderline effects for PAHs and methylene chloride. These results are consistent
with other studies. It is unclear, however, whether these chemicals are risk
factors themselves or if they reflect the effect of a mixture of pollutants.
Future work should include improved spatiotemporal estimates of exposure to air
toxics, taking into account the dynamic movement of individuals during daily
life.
PMID- 26444409
TI - ?
PMID- 26444410
TI - ?
PMID- 26444411
TI - ?
PMID- 26444412
TI - Integration of molecular cytogenetics, dated molecular phylogeny, and model-based
predictions to understand the extreme chromosome reorganization in the
Neotropical genus Tonatia (Chiroptera: Phyllostomidae).
AB - BACKGROUND: Defining factors that contributed to the fixation of a high number of
underdominant chromosomal rearrangements is a complex task because not only
molecular mechanisms must be considered, but also the uniqueness of natural
history attributes of each taxon. Ideally, detailed investigation of the
chromosome architecture of an organism and related groups, placed within a
phylogenetic context, is required. We used multiple approaches to investigate the
dynamics of chromosomal evolution in lineages of bats with considerable
karyotypic variation, focusing on the different facets contributing to fixation
of the exceptional chromosomal changes in Tonatia saurophila. Integration of
empirical data with proposed models of chromosome evolution was performed to
understand the probable conditions for Tonatia's karyotypic evolution. RESULTS:
The trajectory of reorganization of chromosome blocks since the common ancestor
of Glossophaginae and Phyllostominae subfamilies suggests that multiple tandem
fusions, as well as disruption and fusions of conserved phyllostomid chromosomes
were major drivers of karyotypic reshuffling in Tonatia. Considerable variation
in the rates of chromosomal evolution between phyllostomid lineages was observed.
Thirty-nine unique fusions and fission events reached fixation in Tonatia over a
short period of time, followed by ~12 million years of chromosomal stasis.
Physical mapping of repetitive DNA revealed an unusual accumulation of LINE-1
sequences on centromeric regions, probably associated with the chromosomal
dynamics of this genus. CONCLUSIONS: Multiple rearrangements have reached
fixation in a wave-like fashion in phyllostomid bats. Different biological
features of Tonatia support distinct models of rearrangement fixation, and it is
unlikely that the fixations were a result of solely stochastic processes in small
ancient populations. Increased recombination rates were probably facilitated by
expansion of repetitive DNA, reinforced by aspects of taxon reproduction and
ecology.
PMID- 26444414
TI - Rare cause of severe anemia due to pyogenic granuloma in the jejunum.
AB - BACKGROUND: Pyogenic granuloma (PG) is a polypoid lobular capillary hemangioma
rarely observed in the gastrointestinal tract. Only a few cases in the small
bowel have been described in the literature. CASE PRESENTATION: A 58-year-old man
had been suffering from general fatigue and severe anemia.
Esophagogastroduodenoscopy and colonoscopy did not reveal any significant
bleeding. Abdominal computer tomography revealed a hypervascular tumor in the
small intestine. Oral double-balloon endoscopy (DBE) detected a polypoid lesion
(2 cm in diameter) in the jejunum. We performed laparoscopic-assisted partial
resection of the jejunum. The histological features of the tumor were consistent
with PG. The patient's anemia gradually improved without the need for oral iron
after surgery. CONCLUSION: In this case report, we present a case of pyogenic
granuloma in in the jejunum that was detected by DBE.
PMID- 26444413
TI - SLC39A6: a potential target for diagnosis and therapy of esophageal carcinoma.
AB - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer,
and its underlying molecular mechanisms are poorly understood. Recent large-scale
genome-wide association studies in Chinese Han populations have identified an
ESCC susceptibility locus within the SLC39A6 gene. Here, we sought to explore the
expression and biological function of SLC39A6 in ESCC. METHODS: Multiethnic
validation of SLC39A6 protein expression was performed in different cohorts of
patients from Chinese Han and Kazakh populations in the Xinjiang region by
immunohistochemistry. The associations among SLC39A6 expression,
clinicopathological parameters, and prognosis outcomes of ESCC were analyzed. And
the effects of SLC39A6 silencing by siRNA on cell proliferation, apoptosis, and
invasiveness, as well as the proteins involved in epithelial-to-mesenchymal
transition (EMT) of esophageal cancer cells, were studied. RESULTS: SLC39A6
protein expression increased progressively from normal esophageal epithelium
(NEE) to low-grade intraepithelial neoplasia to ESCC, and finally reached the
highest in high-grade intraepithelial neoplasia from Han ethnic. Similarly,
SLC39A6 protein was significantly overexpressed in Kazakh ethnic ESCC compared
with that in NEE. Increased expression of SLC39A6 was found to be closely
correlated with histological grade and early Tumor-Node-Metastasis stage I/II.
High tumorous SLC39A6 expression was significantly correlated with shorter
overall survival (OS). Cox regression analysis confirmed that SLC39A6 expression
was an independent prognostic factor for poor OS in ESCC. Experimentally, the
suppression of SLC39A6 expression promoted ESCC cell apoptosis but abrogated
proliferation and invasion, and induced an EMT phenotype that included enhanced
expression of E-cadherin, loss of vimentin, and morphological changes in ESCC
cells in vitro. CONCLUSIONS: Combined, our findings highlight a tumor-promoting
role for SLC39A6 in ESCC, suggesting that SLC39A6 could serve as an early
detector of high-risk subjects and prognostic biomarker. The targeting of SLC39A6
might be a potential therapeutic strategy for blocking ESCC.
PMID- 26444415
TI - Do users desire symmetrical lumbar supports in task seating?
AB - This research was designed to objectively investigate the desired low back
(lumbar) support in a task chair; specifically by allowing a user to self-select
the magnitude and location of support. An experimental chair built specifically
for this study allowed the users to remotely adjust 35 diodes to achieve their
desired level of support. Pressure mapping was used to measure the interface
pressure at the user-seat back interface. It was determined that 73.8% of the 201
participants in this study, self-selected asymmetrical lower back support that
was at least 20% greater on one side vs. the other. Additionally, 16.9% of the
participants self-selected support on one side which was at least twice that of
the other side. Contrary to popular practice, participants were found to prefer
asymmetric support in the lower back region. It is anticipated that the
culmination of this research will aid chair manufacturers in designing adaptable
back rests. Practitioner Summary: Most current lumbar supports are designed to
move vertically and to symmetrically increase or decrease in firmness as per a
user's adjustment. This investigation highlights that participants tended to
select asymmetrical lumbar support, and as such, designers should consider
providing lumbar supports that provide the desired support at appropriate
locations.
PMID- 26444416
TI - The role of domestic animals in the epidemiology of human African trypanosomiasis
in Ngorongoro conservation area, Tanzania.
AB - BACKGROUND: Trypanosomiasis is a neglected tropical disease caused by the
trypanosome parasite and transmitted by the tsetse fly vector. In Sub-saharan
Africa, both the human and animal variants of the disease are a great obstacle
towards agriculture, development, and health. In order to better understand and
therefore combat Trypanosomiasis, characterizing disease hotspots across species
is critical. METHODS: In this study, 193 samples from cattle, sheep, and goats
were collected from eight sites. Samples were taken from animals belonging mostly
to Maasai herdsmen in the Ngorongoro Crater Conservation Area (NCA) and analysed
for the presence of trypanosomiasis infection using PCR techniques. Those that
tested positive for T. brucei parasite were further tested using SRA LAMP
technique to check for T. brucei rhodesiense, the human infective subspecies of
parasite. RESULTS: Our study found a high incidence of Trypanosoma brucei
infections across species. Of animals tested, 47 % of cattle, 91.7 % of sheep,
and 60.8 % of goats were infected. Most of the infections were of the T. brucei
species. We also identified sheep and goats as carriers of the T. brucei
rhodesiense subspecies, which causes acute human trypanosomiasis. CONCLUSIONS:
Together, these results point toward the need for stricter control strategies in
the area to prevent disease outbreak.
PMID- 26444417
TI - Comparison of characteristics and mortality in multidrug resistant (MDR) and non
MDR tuberculosis patients in China.
AB - BACKGROUND: We conducted a cohort study to compare the characteristics of MDR-TB
with non-MDR-TB patients and to measure long term (9-year) mortality rate and
determine factors associated with death in China. METHODS: We reviewed the
medical records of 250 TB cases from a 2001 survey to compare 100 MDR-TB patients
with 150 non-MDR-TB patients who were treated in 2001-2002. Baseline attributes
extracted from the records were compared between the two cohorts and long-term
mortality and risk factors were determined at nine-year follow-up in 2010.
RESULTS: Among the 234 patients successfully followed up, 63 (26.9%) were female
and 171 (73.1 %) were male. MDR-TB patients had poorer socioeconomic status
compared to non-MDRTB. Nine years after the diagnosis of TB, 69 or 29.5 % of the
234 patients had died (32 or 21.6 % of non-MDR-TB versus 37 or 43.0 % of MDR-TB)
and the overall mortality rate was 39/1000 per year (PY) (27/1000 PY among non
MDR versus 63/1000 PY among MDR-TB). Factors associated with death included: MDR
status (hazard ratio (HR): 1.86; CI: 1.09-3.13), limited education of primary
school or lower (HR: 2.51; CI 1.34-4.70) and received TB treatment during the
nine-year period (HR 1.82; 95 % CI 1.02-3.26). CONCLUSIONS: MDR-TB was a strong
predictor for poor long-term outcome. High quality diagnosis and treatment must
be ensured. Greater reimbursement or free treatment may be needed to provide
access for the poor and vulnerable populations, and to increase treatment
compliance.
PMID- 26444418
TI - Role of cyclooxygenase-1 and -2 in endothelium-dependent contraction of
atherosclerotic mouse abdominal aortas.
AB - The objective of this study was to determine the role of cyclooxygenase (COX)-1
or -2 in endothelium-dependent contraction under atherosclerotic conditions.
Atherosclerosis was induced in apoE knockout (apoE(-/-)) mice and those with COX
1(-/-) (apoE(-/-)-COX-1(-/-)) by feeding with high fat and cholesterol food.
Aortas (abdominal or the whole section) were isolated for functional and/or
biochemical analyses. As in non-atherosclerotic conditions, the muscarinic
receptor agonist acetylcholine (ACh) evoked an endothelium-dependent, COX
mediated contraction following NO synthase (NOS) inhibition in abdominal aortic
rings from atherosclerotic apoE(-/-) mice. Interestingly, COX-1 inhibition not
only abolished such a contraction in rings showing normal appearance, but also
diminished that in rings with plaques. Accordingly, only a minor contraction
(<30% that of apoE(-/-) counterparts) was evoked by ACh (following NOS
inhibition) in abdominal aortic rings of atherosclerotic apoE(-/-)-COX-1(-/-)
mice with plaques, and none was evoked in those showing normal appearance. Also,
the contraction evoked by ACh in apoE(-/-)-COX-1(-/-) abdominal aortic rings with
plaques was abolished by non-selective COX inhibition, thromboxane-prostanoid
(TP) receptor antagonism, or endothelial denudation. Moreover, it was noted that
ACh evoked a predominant production of the prostacyclin (PGI2, which mediates
abdominal aortic contraction via TP receptors in mice) metabolite 6-keto
PGF1alpha, which was again sensitive to COX-1 inhibition or COX-1(-/-).
Therefore, in atherosclerotic mouse abdominal aortas, COX-1 can still be the
major isoform mediating endothelium-dependent contraction, which probably results
largely from PGI2 synthesis as in non-atherosclerotic conditions. In contrast,
COX-2 may have only a minor role in such response limited to areas of plaques
under the same pathological condition.
PMID- 26444419
TI - Enhanced expression of TWIK-related arachidonic acid-activated K+ channel in the
spinal cord of detrusor overactivity rats after partial bladder outlet
obstruction.
AB - BACKGROUND: Detrusor overactivity (DO) secondary to partial bladder outlet
obstruction (PBOO) is closely associated with alteration of ion channels. The
objective of this study is to investigate the expression of the TWIK-related
arachidonic acid-activated K(+) channel (TRAAK) in the L6-S1 spinal cord of DO
rats after PBOO. METHODS: Female Sprague-Dawley rats undergoing PBOO surgery were
screened for DO by cystometry. Sham-operated rats served as controls. The
expression of TRAAK in the L6-S1 spinal cord was detected by real-time polymerase
chain reaction, western blotting and immunohistochemistry. RESULTS: DO was
successfully induced after chronic PBOO in rats, with an incidence rate of 62.5
%. Compared with sham-operated rats, the expression of TRAAK in the L6-S1 spinal
cord of DO rats was significantly increased at the mRNA (1.886 +/- 0.710 versus
0.790 +/- 0.679, P < 0.05) and protein level (0.510 +/- 0.087 versus 0.255 +/-
0.107, P < 0.05). Immunohistochemical staining showed increased expression of
TRAAK in the dorsal horn and ventral horn of the spinal cord. CONCLUSIONS:
Upregulation of TRAAK was observed in the spinal cord of DO rats after chronic
PBOO, which may exert a protective effect against DO by suppressing the
excitability of neurons.
PMID- 26444421
TI - Risk Factors for Multidrug-Resistant Tuberculosis among Patients with Pulmonary
Tuberculosis at the Central Chest Institute of Thailand.
AB - There are limited data available on the risk factors for multidrug-resistant
tuberculosis (MDR-TB). Therefore, we here conducted a retrospective matched case
control study among adults with pulmonary TB who received treatment at the
Central Chest Institute of Thailand (CCIT) between January 2007 and December
2013, in order to determine the risk factors associated with MDR-TB among
patients with pulmonary TB. We identified 145 patients with pulmonary MDR-TB
(cases) and 145 patients with drug-sensitive pulmonary TB (controls).
Multivariate analysis identified the independent risk factors for MDR-TB as
follows: (1) >= 2 episodes of prior pulmonary TB (odds ratio [OR] 39.72, 95%
confidence interval (95% CI) 7.86-200.66), (2) duration of illness > 60 days (OR
3.08, 95% CI 1.52-6.22), (3) sputum acid fast bacilli smear 3+ (OR 13.09, 95% CI
4.64-36.91), (4) presence of lung cavities (OR 3.82, 95% CI 1.89-7.73), and (5)
presence of pleural effusion (OR 2.75, 95% CI 1.06-7.16). Prior pulmonary TB
management with a non-category I regimen (P = 0.012) and having treatment failure
or default as treatment outcomes (P = 0.036) were observed in a higher proportion
among patients with MDR-TB. Particular characteristics of lung cavities,
including the maximum diameter >= 30 mm (P < 0.001), the number of cavities >= 3
(P = 0.001), bilateral involvement (P < 0.001), and >= 2 lung zones involved (P =
0.001) were more commonly observed in patients with MDR-TB. In conclusion, these
clinical factors and chest radiographic findings associated with MDR-TB among
patients with pulmonary TB may help physicians to provide proper management of
cases for prevention of the development and spread of MDR-TB in future.
PMID- 26444420
TI - Leukotriene B4 Enhances NOD2-Dependent Innate Response against Influenza Virus
Infection.
AB - Leukotriene B4 (LTB4), a central mediator of inflammation, is well known for its
chemoattractant properties on effectors cells of the immune system. LTB4 also has
the ability to control microbial infection by improving host innate defenses
through the release of antimicrobial peptides and modulation of intracellular
Toll-like receptors (TLRs) expression in response to agonist challenge. In this
report, we provide evidences that LTB4 acts on nucleotide-binging oligomerization
domain 2 (NOD2) pathway to enhance immune response against influenza A infection.
Infected mice receiving LTB4 show improved survival, lung architecture and
reduced lung viral loads as compared to placebo-treated animals. NOD2 and its
downstream adaptor protein IPS-1 have been found to be essential for LTB4
mediated effects against IAV infection, as absence of NOD2 or IPS-1 diminished
its capacity to control viral infection. Treatment of IAV-infected mice with LTB4
induces an increased activation of IPS-1-IRF3 axis leading to an enhanced
production of IFNbeta in lungs of infected mice. LTB4 also has the ability to act
on the RICK-NF-kappaB axis since administration of LTB4 to mice challenged with
MDP markedly increases the secretion of IL-6 and TNFalpha in lungs of mice. TAK1
appears to be essential to the action of LTB4 on NOD2 pathway since pretreatment
of MEFs with TAK1 inhibitor prior stimulation with IAV or MDP strongly abrogated
the potentiating effects of LTB4 on both IFNbeta and cytokine secretion.
Together, our results demonstrate that LTB4, through its ability to activate
TAK1, potentiates both IPS-1 and RICK axis of the NOD2 pathway to improve host
innate responses.
PMID- 26444422
TI - CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and
Interferon-gamma Production In Vivo.
AB - Upon their recognition of antigens presented by the MHC, T cell proliferation is
vital for clonal expansion and the acquisition of effector functions, which are
essential for mounting adaptive immune responses. The CD98 heavy chain (CD98hc,
Slc3a2) plays a crucial role in the proliferation of both CD4+ and CD8+ T cells,
although it is unclear if CD98hc directly regulates the T cell effector functions
that are not linked with T cell proliferation in vivo. Here, we demonstrate that
CD98hc is required for both CD4+ T cell proliferation and Th1 functional
differentiation. T cell-specific deletion of CD98hc did not affect T cell
development in the thymus. CD98hc-deficient CD4+ T cells proliferated in vivo
more slowly as compared with control T cells. C57BL/6 mice lacking CD98hc in
their CD4+ T cells could not control Leishmania major infections due to lowered
IFN-gamma production, even with massive CD4+ T cell proliferation. CD98hc
deficient CD4+ T cells exhibited lower IFN-gamma production compared with wild
type T cells, even when comparing IFN-gamma expression in cells that underwent
the same number of cell divisions. Therefore, these data indicate that CD98hc is
required for CD4+ T cell expansion and functional Th1 differentiation in vivo,
and suggest that CD98hc might be a good target for treating Th1-mediated immune
disorders.
PMID- 26444424
TI - Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or
Combination Therapy in Patients with Clostridium difficile Infection: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Clostridium difficile infection (CDI) has become a global
epidemiological problem for both hospitalized patients and outpatients. The most
commonly used drugs to treat CDI are metronidazole and vancomycin. The aim of
this study was to compare the efficacy and safety of metronidazole monotherapy
with vancomycin monotherapy and combination therapy in CDI patients. METHODS: A
comprehensive search without publication status or other restrictions was
conducted. Studies comparing metronidazole monotherapy with vancomycin
monotherapy or combination therapy in patients with CDI were considered eligible.
Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and
odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated and
reported. RESULTS: Of the 1910 records identified, seventeen studies from
thirteen articles (n = 2501 patients) were included. No statistically significant
difference in the rate of clinical cure was found between metronidazole and
vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00), p = 0.05) or between
either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58,
1.96), p = 0.83); however, the rate of clinical cure was lower for metronidazole
than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80), p = 0.006).
No statistically significant difference in the rate of CDI recurrence was found
between metronidazole and vancomycin for mild CDI (OR = 0.99, 95% CI (0.40,
2.45), p = 0.98) or severe CDI (OR = 0.98, 95% CI (0.63, 1.53), p = 0.94) or
between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI
(0.66, 1.26), p = 0.56). In addition, there was no significant difference in the
rate of adverse events (AEs) between metronidazole and vancomycin (OR = 1.18, 95%
CI (0.80, 1.74), p = 0.41). In contrast, the rate of AEs was significantly lower
for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17,
0.51), p < 0.0001). CONCLUSIONS: Metronidazole and vancomycin are equally
effective for the treatment of mild CDI, but vancomycin is superior for the
treatment of severe CDI. Combination therapy is not superior to monotherapy
because it appears to be associated with an increase in the rate of AEs.
PMID- 26444423
TI - An Oriental Medicine, Hyungbangpaedok-San Attenuates Motor Paralysis in an
Experimental Model of Multiple Sclerosis by Regulating the T Cell Response.
AB - The preventive and therapeutic mechanisms in multiple sclerosis are not clearly
understood. We investigated whether Hyungbangpaedok-san (HBPDS), a traditional
herbal medicine, has a beneficial effect in experimental autoimmune
encephalomyelitis (EAE) mice immunized with myelin oligodendrocyte glycoprotein
peptide (MOG 35-55). Onset-treatment with 4 types of HBPDS (extracted using
distilled water and 30%/70%/100% ethanol as the solvent) alleviated neurological
signs, and HBPDS extracted within 30% ethanol (henceforth called HBPDS) was more
effective. Onset-treatment with HBPDS reduced demyelination and the
recruitment/infiltration and activation of microglia/macrophages in the spinal
cord of EAE mice, which corresponded to the reduced mRNA expression of pro
inflammatory cytokines (TNF-alpha, IL-6, and IL-1beta), iNOS, and chemokines (MCP
1, MIP-1alpha, and RANTES) in the spinal cord. Onset-treatment with HBPDS
inhibited changes in the components of the blood-brain barrier such as
astrocytes, adhesion molecules (ICAM-1 and VCAM-1), and junctional molecules
(claudin-3, claudin-5, and zona occludens-1) in the spinal cord of EAE mice.
Onset-treatment with HBPDS reduced the elevated population of CD4+, CD4+/IFN
gamma+, and CD4+/IL-17+ T cells in the spinal cord of EAE mice but it further
increased the elevated population of CD4+/CD25+/Foxp3+ and CD4+/Foxp3+/Helios+ T
cells. Pre-, onset-, post-, but not peak-treatment, with HBPDS had a beneficial
effect on behavioral impairment in EAE mice. Taken together, HBPDS could
alleviate the development/progression of EAE by regulating the
recruitment/infiltration and activation of microglia and peripheral immune cells
(macrophages, Th1, Th17, and Treg cells) in the spinal cord. These findings could
help to develop protective strategies using HBPDS in the treatment of autoimmune
disorders including multiple sclerosis.
PMID- 26444425
TI - Molecular Characterization and Expression Profiling of NAC Transcription Factors
in Brachypodium distachyon L.
AB - NAC (NAM, ATAF1/2, CUC2) transcription factors are involved in regulating plant
developmental processes and response to environmental stresses. Brachypodium
distachyon is an emerging model system for cereals, temperate grasses and biofuel
crops. In this study, a comprehensive investigation of the molecular
characterizations, phylogenetics and expression profiles under various abiotic
stresses of the NAC gene family in Brachypodium distachyon was performed. In
total, 118 BNAC genes in B. distachyon were identified, of which 22 (18.64%) were
tandemly duplicated and segmentally duplicated, respectively. The Bayesian
phylogenetic inference using Markov Chain Monte Carlo (MCMC) algorithms showed
that they were divided into two clades and fourteen subfamilies, supported by
similar motif compositions within one subfamily. Some critical amino acids
detected using DIVERGE v3.0 might contribute to functional divergence among
subfamilies. The different exon-intron organizations among subfamilies revealed
structural differentiation. Promoter sequence predictions showed that the BNAC
genes were involved in various developmental processes and diverse stress
responses. Three NAC domain-encoding genes (BNAC012, BNAC078 and BNAC108),
orthologous of NAC1, were targeted by five miRNA164 (Bdi-miR164a-c, e, f),
suggesting that they might function in lateral organ enlargement, floral
development and the responses to abiotic stress. Eleven (~9.32%) BNAC proteins
containing alpha-helical transmembrane motifs were identified. 23 representative
BNAC genes were analyzed by quantitative real-time PCR, showing different
expression patterns under various abiotic stresses, of which 18, 17 and 11 genes
were up-regulated significantly under drought, H2O2 and salt stresses,
respectively. Only four and two genes were up-regulated under cold and cadmium
stresses, respectively. Dynamic transcriptional expression analysis revealed that
six genes showed constitutive expression and period-specific expression. The
current results provide novel insights into the structure and function of the
plant NAC gene family.
PMID- 26444427
TI - Schleyer hyperconjugative aromaticity and Diels-Alder reactivity of 5-substituted
cyclopentadienes.
AB - Schleyer's discovery of hyperconjugative aromaticity and antiaromaticity in 5
substituted cyclopentadienes further expanded our understanding of the pervasive
influence of aromaticity. Acceptors induce antiaromatic character by Schleyer's
negative hyperconjugative aromaticity, and donors have the opposite effect. We
computationally explored the Diels-Alder reactivity of 5-substituted
cyclopentadienes with ethylene and maleic anhydride. The predicted billionfold
difference in the computed gas phase rate constants at room temperature for the
Diels-Alder reactions of 5-substituted cyclopentadienes with ethylene or maleic
anhydride results from differences in the transition state distortion energies,
which are directly related to the hyperconjugative aromaticity of these
molecules.
PMID- 26444426
TI - Gait Biomechanics and Patient-Reported Function as Predictors of Response to a
Hip Strengthening Exercise Intervention in Patients with Knee Osteoarthritis.
AB - OBJECTIVE: Muscle strengthening exercises have been shown to improve pain and
function in adults with mild-to-moderate knee osteoarthritis, but individual
response rates can vary greatly. Predicting individuals who respond and those who
do not is important in developing a more efficient and effective model of care
for knee osteoarthritis (OA). Therefore, the purpose of this study was to use pre
intervention gait kinematics and patient-reported outcome measures to predict
post-intervention response to a 6-week hip strengthening exercise intervention in
patients with mild-to-moderate knee OA. METHODS: Thirty-nine patients with mild
to-moderate knee osteoarthritis completed a 6-week hip-strengthening program and
were subgrouped as Non-Responders, Low-Responders, or High-Responders following
the intervention based on their change in Knee injury Osteoarthritis Outcome
Score (KOOS). Predictors of responder subgroups were retrospectively determined
from baseline patient-reported outcome measures and kinematic gait parameters in
a discriminant analysis of principal components. A 3-4 year follow-up on 16 of
the patients with knee OA was also done to examine long-term changes in these
parameters. RESULTS: A unique combination of patient-reported outcome measures
and kinematic factors was able to successfully subgroup patients with knee
osteoarthritis with a cross-validated classification accuracy of 85.4%. Lower
patient-reported function in daily living (ADL) scores and hip frontal plane
kinematics during the loading response were most important in classifying High
Responders from other sub-groups, while a combination of hip, knee, ankle
kinematics were used to classify Non-Responders from Low-Responders. CONCLUSION:
Patient-reported outcome measures and objective biomechanical gait data can be an
effective method of predicting individual treatment success to an exercise
intervention. Measuring gait kinematics, along with patient-reported outcome
measures in a clinical setting can be useful in helping make evidence-based
decisions regarding optimal treatment for patients with knee OA.
PMID- 26444428
TI - Comparing the Rates of Early Childhood Victimization across Sexual Orientations:
Heterosexual, Lesbian, Gay, Bisexual, and Mostly Heterosexual.
AB - Few studies have examined the rates of childhood victimization among individuals
who identify as "mostly heterosexual" (MH) in comparison to other sexual
orientation groups. For the present study, we utilized a more comprehensive
assessment of adverse childhood experiences to extend prior literature by
examining if MH individuals' experience of victimization more closely mirrors
that of sexual minority individuals or heterosexuals. Heterosexual (n = 422) and
LGB (n = 561) and MH (n = 120) participants were recruited online. Respondents
completed surveys about their adverse childhood experiences, both maltreatment by
adults (e.g., childhood physical, emotional, and sexual abuse and childhood
household dysfunction) and peer victimization (i.e., verbal and physical
bullying). Specifically, MH individuals were 1.47 times more likely than
heterosexuals to report childhood victimization experiences perpetrated by
adults. These elevated rates were similar to LGB individuals. Results suggest
that rates of victimization of MH groups are more similar to the rates found
among LGBs, and are significantly higher than heterosexual groups. Our results
support prior research that indicates that an MH identity falls within the
umbrella of a sexual minority, yet little is known about unique challenges that
this group may face in comparison to other sexual minority groups.
PMID- 26444429
TI - Clinical effect of cardiac shock wave therapy on patients with ischaemic heart
disease: a systematic review and meta-analysis.
AB - BACKGROUND: After several years of study, CSWT has been initially applied to IHD
treatment, but the actual effectiveness has never been well evaluated with a meta
analysis. METHODS: MEDLINE, EMBASE, Science Direct, Cochrane Controlled Trials
Register database and Chinese database were searched. The randomized controlled
trials, and single-arm and cohort study related to in patients with IHD
undergoing CSWT were included and 14 articles were finally analysed. The data
related to the study design, patient characteristics and outcomes were extracted.
All the selected data were calculated with random-effects models in weighted mean
differences, and heterogeneity was carefully evaluated as well. RESULTS: (i)
Cardiac shock wave therapy improves the angina pectoris symptom (including the
decrease of Canadian Cardiovascular Society class [-0.86 (-1.12, -0.65), P <
0.00001], nitroglycerin dosage (times/weeks) [-0.71 (-1.08, -0.33), P = 0.0002]
and a increase of Seattle Angina Questionnaire score [5.64 (3.12, 8.15), P <
0.0001)]); (ii) CSWT leads to a reduce in heart failure (including a reduction of
New York Heart Association functional class [-0.49 (-0.62, -0.37), P < 0.00001],
a stable rise in 6-min walking distance [68.38 (39.70, 97.05), P < 0.00001] and a
growth in left ventricular ejection fraction with echocardiography screening
[6.73 (4.67,8.80), P < 0.00001]); (iii) CSWT improves myocardial viability within
improving in total score of perfusion imaging [-5.19 (-8.08, -2.30), P = 0.0004]
and total score of metabolism imaging [-5.33 (-7.77, -2.90), P < 0.0001].
CONCLUSIONS: The meta-analysis suggests that CSWT may offer beneficial effects to
patients with IHD, although there was significant heterogeneity across the
studies.
PMID- 26444430
TI - Inflammation Induces TDP-43 Mislocalization and Aggregation.
AB - TAR DNA-binding protein 43 (TDP-43) is a major component in aggregates of
ubiquitinated proteins in amyotrophic lateral sclerosis (ALS) and frontotemporal
lobar degeneration (FTLD). Here we report that lipopolysaccharide (LPS)-induced
inflammation can promote TDP-43 mislocalization and aggregation. In culture,
microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS.
Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF
alpha) increased the cytoplasmic levels of TDP-43. In addition, the chronic
intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T) transgenic
mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal
motor neurons and it enhanced the levels of TDP-43 aggregation. These results
suggest that inflammation may contribute to development or exacerbation of TDP-43
proteinopathies in neurodegenerative disorders.
PMID- 26444431
TI - New Insights into Butyrylcholinesterase Activity Assay: Serum Dilution Factor as
a Crucial Parameter.
AB - Butyrylcholinesterase (BChE) activity assay and inhibitor phenotyping can help to
identify patients at risk of prolonged paralysis following the administration of
neuromuscular blocking agents. The assay plays an important role in clinical
chemistry as a good diagnostic marker for intoxication with pesticides and nerve
agents. Furthermore, the assay is also commonly used for in vitro
characterization of cholinesterases, their toxins and drugs. There is still lack
of standardized procedure for measurement of BChE activity and many laboratories
use different substrates at various concentrations. The purpose of this study was
to validate the BChE activity assay to determine the best dilution of human serum
and the most optimal concentration of substrates and inhibitors. Serum BChE
activity was measured using modified Ellman's method applicable for a microplate
reader. We present our experience and new insights into the protocol for high
throughput routine assays of human plasma cholinesterase activities adapted to a
microplate reader. During our routine assays used for the determination of BChE
activity, we have observed that serum dilution factor influences the results
obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine
iodide can be successfully used for the accurate measurement of BChE activity in
human serum. We also discuss usage of various concentrations of dibucaine and
fluoride in BChE phenotyping. This study indicates that some factors of such a
multicomponent clinical material like serum can influence kinetic parameters of
the BChE. The observed inhibitory effect is dependent on serum dilution factor
used in the assay.
PMID- 26444433
TI - Supramolecular bimetallic assemblies for photocatalytic hydrogen generation from
water.
AB - A series of supramolecular assemblies of the type [Ru(L-L)2(L'-L)MX2)](n+) are
reported where L-L is 2,2'-bipyridine (bipy), 4,4'-di-tetra-butyl-bipyridine
(tbbipy) or 4,4'-diethoxycarbonyl-2,2'-bipyridine (dceb), L-L' is tetrapyrido[3,2
a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine (tpphz), 2,2':5',2''-terpyridine (2,5
bpp), 2,2':6',2''-terpyridine, (2,6-bpp), 2,5-di(pyridine-2-yl)pyrazine (2,5-dpp)
or 2,3-di(pyridine-2-yl)pyrazine (2,3-dpp), and MX2 is PdCl2, PtCl2 or PtI2. The
photocatalytic behaviour with respect to hydrogen generation of these compounds
and their ultrafast photophysical properties are discussed as a function of the
nature of the peripheral ligands, the bridging ligands and the catalytic centre.
The results obtained show how differences in the chemical composition of the
photocatalysts can affect intramolecular photoinduced electron transfer processes
and the overall photocatalytic efficiency.
PMID- 26444432
TI - Effects of Pyriproxyfen on Female Reproduction in the Common Cutworm, Spodoptera
litura (F.) (Lepidoptera: Noctuidae).
AB - The common cutworm, Spodoptera litura, is a rapidly reproducing pest of numerous
agricultural ecosystems worldwide. The use of pesticides remains the primary
means for controlling S. litura, despite their negative ecological impact and
potential threat to human health. The use of exogenous hormone analogs may
represent an alternative to insecticides. Juvenile hormones (JHs) play an
important role in the reproductive systems of female insects, but the effects of
pyriproxyfen, a JH analog, on reproduction in S. litura were poorly understood.
In this paper, we topically treated the newly emerged females with 20, 60, or 100
MUg of pyriproxyfen to determine its effects on reproduction. Then, we examined
the expression of vitellogenin (Vg) and three hormone receptors, USP, HR3, and
EcR, using quantitative reverse transcription and real-time polymerase chain
reaction (qRT-PCR), and found that pyriproxyfen up-regulated the expression of
Vg, USP, and HR3, whereas the expression of EcR was unaffected. An analysis of
fecundity showed that the peak oviposition day, lifespan, and oviposition period
were progressively shortened as the pyriproxyfen dosage increased. We also found
that pyriproxyfen decreased egg laying amount, whereas the number of mature eggs
that remained in the ovarioles of dead females increased as the pyriproxyfen
dosage increased. We examined oocytes using transmission electron microscopy and
found that treatment with 100 MUg of pyriproxyfen increased the metabolism by
increasing the amount of rough endoplasmic reticulum and mitochondria in the
primary oocytes. Our results suggest that the topical application of pyriproxyfen
on newly emerged females can efficiently reduce reproduction in S. litura and may
represent an alternative to the use of insecticides for controlling the
agricultural pest.
PMID- 26444435
TI - A flexible AFT model for misclassified clustered interval-censored data.
AB - Motivated by a longitudinal oral health study, we propose a flexible modeling
approach for clustered time-to-event data, when the response of interest can only
be determined to lie in an interval obtained from a sequence of examination times
(interval-censored data) and on top of that, the determination of the occurrence
of the event is subject to misclassification. The clustered time-to-event data
are modeled using an accelerated failure time model with random effects and by
assuming a penalized Gaussian mixture model for the random effects terms to avoid
restrictive distributional assumptions concerning the event times. A general
misclassification model is discussed in detail, considering the possibility that
different examiners were involved in the assessment of the occurrence of the
events for a given subject across time. A Bayesian implementation of the proposed
model is described in a detailed manner. We additionally provide empirical
evidence showing that the model can be used to estimate the underlying time-to
event distribution and the misclassification parameters without any external
information about the latter parameters. We also provide results of a simulation
study to evaluate the effect of neglecting the presence of misclassification in
the analysis of clustered time-to-event data.
PMID- 26444434
TI - Importance of the Side Chain at Position 296 of Antibody Fc in Interactions with
FcgammaRIIIa and Other Fcgamma Receptors.
AB - Antibody-dependent cellular cytotoxicity (ADCC) is an important effector function
determining the clinical efficacy of therapeutic antibodies. Core fucose removal
from N-glycans on the Fc portion of immunoglobulin G (IgG) improves the binding
affinity for Fcgamma receptor IIIa (FcgammaRIIIa) and dramatically enhances ADCC.
Our previous structural analyses revealed that Tyr-296 of IgG1-Fc plays a
critical role in the interaction with FcgammaRIIIa, particularly in the enhanced
FcgammaRIIIa binding of nonfucosylated IgG1. However, the importance of the Tyr
296 residue in the antibody in the interaction with various Fcgamma receptors has
not yet been elucidated. To further clarify the biological importance of this
residue, we established comprehensive Tyr-296 mutants as fucosylated and
nonfucosylated anti-CD20 IgG1s rituximab variants and examined their binding to
recombinant soluble human Fcgamma receptors: shFcgammaRI, shFcgammaRIIa,
shFcgammaRIIIa, and shFcgammaRIIIb. Some of the mutations affected the binding of
antibody to not only shFcgammaRIIIa but also shFcgammaRIIa and shFcgammaRIIIb,
suggesting that the Tyr-296 residue in the antibody was also involved in
interactions with FcgammaRIIa and FcgammaRIIIb. For FcgammaRIIIa binding, almost
all Tyr-296 variants showed lower binding affinities than the wild-type antibody,
irrespective of their core fucosylation, particularly in Y296K and Y296P.
Notably, only the Y296W mutant showed improved binding to FcgammaRIIIa. The 3.00
A-resolution crystal structure of the nonfucosylated Y296W mutant in complex with
shFcgammaRIIIa harboring two N-glycans revealed that the Tyr-to-Trp substitution
increased the number of potential contact atoms in the complex, thus improving
the binding of the antibody to shFcgammaRIIIa. The nonfucosylated Y296W mutant
retained high ADCC activity, relative to the nonfucosylated wild-type IgG1, and
showed greater binding affinity for FcgammaRIIa. Our data may improve our
understanding of the biological importance of human IgG1-Fc Tyr-296 in
interactions with various Fcgamma receptors, and have applications in the
modulation of the IgG1-Fc function of therapeutic antibodies.
PMID- 26444436
TI - Flexible thin-film battery based on graphene-oxide embedded in solid polymer
electrolyte.
AB - Enhanced safety of flexible batteries is an imperative objective due to the
intimate interaction of such devices with human organs such as flexible batteries
that are integrated with touch-screens or embedded in clothing or space suits. In
this study, the fabrication and testing of a high performance thin-film Li-ion
battery (LIB) is reported that is both flexible and relatively safer compared to
the conventional electrolyte based batteries. The concept is facilitated by the
use of solid polymer nanocomposite electrolyte, specifically, composed of
polyethylene oxide (PEO) matrix and 1 wt% graphene oxide (GO) nanosheets. The
flexible LIB exhibits a high maximum operating voltage of 4.9 V, high capacity of
0.13 mA h cm(-2) and an energy density of 4.8 mW h cm(-3). The battery is
encapsulated using a simple lamination method that is economical and scalable.
The laminated battery shows robust mechanical flexibility over 6000 bending
cycles and excellent electrochemical performance in both flat and bent
configurations. Finite element analysis (FEA) of the LIB provides critical
insights into the evolution of mechanical stresses during lamination and bending.
PMID- 26444437
TI - Improving the productivity of 19,20-epoxy-cytochalasin Q in Xylaria sp. sof11
with culture condition optimization.
AB - 19,20-Epoxy-cytochalasin Q (B5A) is a cytochalasin with a wide range of
biological activities, which can be produced by Xylaria sp. sof11, a strain
isolated from the seafloor of the northern South China Sea. Since the low titer
of B5A has greatly limited its further studies, we have systematically conducted
the fermentative optimization for B5A production in this article. The effects of
major medium components, including the carbon and organic nitrogen sources, as
well as of the concentration of sea salt, were respectively investigated through
single-factor experiments. As a result, sucrose and fish meal were determined to
be the key factors affecting the production of B5A. Then three important
variables, sucrose, fish meal, and filling volume, were screened out by the
Plackett-Burman (PB) design. The optimal level of these variables was further
confirmed by response surface analysis. The final formulated medium was set as
35.2 g/L sucrose and 18.0 g/L fish meal, with filling volume of 34.6 mL, which
could afford 440.3 mg/L production of B5A, approximately 4.4-fold higher than
that in the original medium. The significantly improved productivity of B5A will
facilitate the subsequent mechanistic and clinical studies of B5A.
PMID- 26444438
TI - Cryptococcal meningitis due to Cryptococcus neoformans genotype AFLP1/VNI in
Iran: a review of the literature.
AB - Cryptococcal meningitis is the most important opportunistic fungal infection with
a high mortality in HIV-patients in less developed regions. Here, we report a
case of cryptococcal meningitis in a 49-year-old HIV-positive female due to
Cryptococcus neoformans (serotype A, mating-type alpha, genotype AFLP1/VNI) in
Sari, Iran. In vitro antifungal susceptibility tests showed MICs of isavuconazole
(0.016 MUg ml(-1) ), voriconazole (0.031 MUg ml(-1) ), posaconazole (0.031 MUg
ml(-1) ), itraconazole (0.063 MUg ml(-1) ), amphotericin B (0.125 MUg ml(-1) )
and fluconazole (8 MUg ml(-1) ). Despite immediate antifungal therapy, the
patient died 4 days later due to respiratory failure. Cryptococcal infections
have been infrequently reported from Iran and therefore we analysed all published
cases of cryptococcosis in Iran since the first reported case from 1969.
PMID- 26444439
TI - Important factors determining the nanoscale tracking precision of dynamic
microtubule ends.
AB - Tracking dynamic microtubule ends in fluorescence microscopy movies provides
insight into the statistical properties of microtubule dynamics and is vital for
further analysis that requires knowledge of the trajectories of the microtubule
ends. Here we analyse the performance of a previously developed automated
microtubule end tracking routine; this has been optimized for comparatively low
signal-to-noise image sequences that are characteristic of microscopy movies of
dynamic microtubules growing in vitro. Sequences of simulated microtubule images
were generated assuming a variety of different experimental conditions. The
simulated movies were then tracked and the tracking errors were characterized. We
found that the growth characteristics of the microtubules within realistic ranges
had a negligible effect on the tracking precision. The fluorophore labelling
density, the pixel size of the images, and the exposure times were found to be
important parameters limiting the tracking precision which could be explained
using concepts of single molecule localization microscopy. The signal-to-noise
ratio was found to be a good single predictor of the tracking precision: typical
experimental signal-to-noise ratios lead to tracking precisions in the range of
tens of nanometres, making the tracking program described here a useful tool for
dynamic microtubule end tracking with close to molecular precision.
PMID- 26444440
TI - Changes in Volatile Compounds of Chinese Luzhou-Flavor Liquor during the
Fermentation and Distillation Process.
AB - The aim of this study was to investigate the dynamic of volatile compounds in the
Zaopei during the fermentation and distillation process by headspace solid-phase
microextraction-gas chromatography mass spectrometry (HS-SPME-GCMS).
Physicochemical properties analysis of Zaopei (fermented grains [FG], fermented
grains mixed with sorghum [FGS], streamed grains [SG], and streamed grains mixed
with Daqu [SGD]) showed distinct changes. A total number of 66 volatile compounds
in the Zaopei were identified, in which butanoic acid, hexanoic acid, ethyl
hexanoate, ethyl lactate, ethyl octanoate, hexyl hexanoate, ethyl hydrocinnamate,
ethyl oleate, ethyl hexadecanoate, and ethyl linoleate were considered to be the
dominant compounds due to their high concentrations. FG had the highest volatile
compounds (112.43 mg/kg), which significantly decreased by 17.05% in the FGS,
67.12% in the SG, and 73.75% in the SGD. Furthermore, about 61.49% of volatile
compounds of FGS were evaporated into raw liquor, whereas head, heart, and tail
liquor accounted for 29.84%, 39.49%, and 30.67%, respectively. Each volatile
class generally presented a decreasing trend, except for furans. Especially, the
percentage of esters was 55.51% to 67.41% in the Zaopei, and reached 92.60% to
97.67% in the raw liquor. Principal component analysis based ordination of
volatile compounds data segregated FGS and SGD samples. In addition, radar
diagrams of the odor activity values suggested that intense flavor of fruit was
weakened most from FG to SGD. PRACTICAL APPLICATION: The dynamic of volatile
compounds in the Zaopei during the fermentation and distillation process was
tested by SPME-GCMS. The result of this study demonstrated that both volatile
compounds of Zaopei and thermal reaction during distillation simply determined
the unique feature of raw liquor. This study was conducted based on the real
products from liquor manufactory, so it is practicable that the method can be
used in an industry setting.
PMID- 26444442
TI - Assessing Toxicity of Intravenous Crystalloids in Critically Ill Patients.
PMID- 26444441
TI - The Epidemiology of Alcohol Use and Alcohol Use Disorders among Young People in
Northern Tanzania.
AB - INTRODUCTION: Alcohol use is a global public health problem, including as a risk
factor for HIV infection, but few data are available on the epidemiology of
alcohol use and alcohol use disorders (AUD) among young people in sub-Saharan
Africa. METHODS: We conducted a cross-sectional survey among 4 groups of young
people aged 15-24 years old (secondary school students, college/university
students, employees of local industries and casual labourers) in two regions
(Kilimanjaro and Mwanza) of northern Tanzania. Using a multistage stratified
random sampling strategy, we collected information on demographics, alcohol use,
and behavioural factors. We screened severity of alcohol use using the Alcohol
Use Disorder Identification Test (AUDIT) and estimated the quantity and frequency
of alcohol consumption using the timeline-follow-back-calendar (TLFB) method.
RESULTS: A total of 1954 young people were surveyed. The prevalence of reported
alcohol use was higher among males (47-70% ever users and 20-45% current users)
than females (24-54% ever users and 12-47% current users). Prevalence of use was
substantially higher in Kilimanjaro than Mwanza region. In both regions,
participants reported high exposure to alcohol advertisements, and wide alcohol
availability. College students reported the highest prevalence of current alcohol
use (45% among males; 26% among females) and of heavy episodic drinking (71%
among males; 27% among females) followed by casual labourers. Males were more
likely to have AUD (an AUDIT score >=8) than females, with 11-28% of males
screening positive for AUD. Alcohol use was associated with male gender, being in
a relationship, greater disposable income, non-Muslim religion and a higher
number of sexual partners. CONCLUSIONS: Alcohol use is a significant problem
among young people in northern Tanzania. There is an urgent need to develop,
pilot and deliver interventions to help young people delay initiation and reduce
levels of harmful drinking, particularly among college students and casual
labourers.
PMID- 26444443
TI - The effect of various electrolyte cations on electrochemical performance of
polypyrrole/RGO based supercapacitors.
AB - In this work, polypyrrole/graphene doped by p-toluenesulfonic is prepared as an
active material for supercapacitors, and its capacitance performance is
investigated in various aqueous electrolytes including HCl, LiCl, NaCl, and KCl
with a concentration of 3 M, respectively. A rising trend of capacitance is
observed according to the cationic mobility (Li(+) < Na(+) < K(+) < H(+)), which
is due to its effect on the ionic conductivity, efficient ion/charge
diffusion/exchange and relaxation time. On the other hand, long-term cycling
stability is in the following order: KCl < NaCl < LiCl < HCl, corresponding to
the decreasing tendency of cation size (K(+) > Na(+) > Li(+) > H(+)). The reason
can be attributed to the fact that the insertion/de-insertion of large size
cation brings a significant doping level decrease and an over-oxidation increase
during the charging-discharging cycles. Hence, we not only obtain good
capacitance performance (280.3 F g(-1) at 5 mV s(-1)), superior rate capability
(225.8 F g(-1) at 500 mV s(-1)) and high cycling stability (92.0% capacitance
retention after 10,000 cycles at 1 A g(-1)) by employing 3 M HCl as an
electrolyte, but also reveal that the electrolyte cations have a significant
effect on the supercapacitors' electrochemical performance.
PMID- 26444444
TI - Self-harm Emergencies After Bariatric Surgery: A Population-Based Cohort Study.
AB - IMPORTANCE: Self-harm behaviors, including suicidal ideation and past suicide
attempts, are frequent in bariatric surgery candidates. It is unclear, however,
whether these behaviors are mitigated or aggravated by surgery. OBJECTIVE: To
compare the risk of self-harm behaviors before and after bariatric surgery.
DESIGN, SETTING, AND PARTICIPANTS: In this population-based, self-matched,
longitudinal cohort analysis, we studied 8815 adults from Ontario, Canada, who
underwent bariatric surgery between April 1, 2006, and March 31, 2011. Follow-up
for each patient was 3 years prior to surgery and 3 years after surgery. MAIN
OUTCOMES AND MEASURES: Self-harm emergencies 3 years before and after surgery.
RESULTS: The cohort included 8815 patients of whom 7176 (81.4%) were women, 7063
(80.1%) were 35 years or older, and 8681 (98.5%) were treated with gastric
bypass. A total of 111 patients had 158 self-harm emergencies during follow-up.
Overall, self-harm emergencies significantly increased after surgery (3.63 per
1000 patient-years) compared with before surgery (2.33 per 1000 patient-years),
equaling a rate ratio (RR) of 1.54 (95% CI, 1.03-2.30; P = .007). Self-harm
emergencies after surgery were higher than before surgery among patients older
than 35 years (RR, 1.76; 95% CI, 1.05-2.94; P = .03), those with a low-income
status (RR, 2.09; 95% CI, 1.20-3.65; P = .01), and those living in rural areas
(RR, 6.49; 95% CI, 1.42-29.63; P = .02). The most common self-harm mechanism was
an intentional overdose (115 [72.8%]). A total of 147 events (93.0%) occurred in
patients diagnosed as having a mental health disorder during the 5 years before
the surgery. CONCLUSIONS AND RELEVANCE: In this study, the risk of self-harm
emergencies increased after bariatric surgery, underscoring the need for
screening for suicide risk during follow-up.
PMID- 26444445
TI - Guided inquiry activities for learning about the macro- and micronutrients in
introductory nutrition courses.
AB - Most students enroll in general education introductory nutrition classes because
they want to improve their diets in order to lose weight or enhance athletic
performance. These nonscience majors are often less interested in learning about
the fundamental biochemical principles underlying nutrition or are surprised that
this foundational knowledge of biochemistry is essential for appropriate diet
planning. Furthermore, nonscience majors sometimes find traditional, lecture
oriented science classes that encourage competition rather than collaboration to
be uninviting and unappealing. For these reasons, we have developed a set of
guided inquiry activities about macronutrients (carbohydrates, lipids, and
proteins) and micronutrients (vitamins and minerals) for use in introductory
nutrition courses for nonscience majors. In our first study (Spring 2012), we
divided students into two groups with two different approaches for learning about
the macronutrients: (1) a traditional, lecture-based approach and (2) an active
learning approach with guided inquiry activities. We showed through the use of
embedded common exam questions that students mastered concepts related to the
macronutrients equally well using either approach. Due to positive student and
faculty feedback from the first study, we decided to have all students use the
guided inquiry approach in a subsequent study the following year (Spring 2013).
In our second study we used pre/post survey data to evaluate both students'
concept mastery and confidence in answering questions about the macro- and
micronutrients. We found that (1) students showed gains in both concept mastery
and confidence and (2) as students' confidence increased, post-test concept
scores also increased.
PMID- 26444446
TI - Corticosteroids as co-analgesics with opioids for cancer pain: a survey of
Australian and New Zealand palliative care clinicians.
AB - Corticosteroids are commonly used as co-analgesics with opioids for cancer pain;
however limited quality data exist supporting their efficacy for this purpose.
Further, little is known about individual prescribing practices. The current
study surveyed members of the Australian New Zealand Society of Palliative
Medicine about their use of corticosteroids as adjuvant analgesics in cancer
pain. It confirmed high rates of utilisation and found variability in starting
doses and associated decision-making. Further research is required to determine
the efficacy and safety of corticosteroids as co-analgesics in cancer pain
management.
PMID- 26444447
TI - Cultural Competence Among Italian Nurses: A Multicentric Survey.
AB - PURPOSE: To assess Italian nurses' cultural competence, as they are increasingly
called upon to care for people of foreign origins. DESIGN: A cross-sectional,
multicentric study. METHODS: From September 2013 to May 2014, a survey was
carried out among Italian nurses. Cultural competence was assessed by the
Cultural Competence Assessment tool, translated and adapted to the Italian
context. FINDINGS: Nurses who completed the survey numbered 1,432; 70.6% were
female; 42.6% ranged in age from 41 to 50 years; and 50.0% were bachelor's
prepared. More than 50% had participated in some kind of cultural diversity
training. Overall, cultural competence was moderate, showing a moderately high
level of cultural awareness and sensitivity (mean = 5.41; SD = 0.66) and a
moderate level of culturally competent behaviors (mean = 4.33; SD = 1.10).
CONCLUSIONS: Although Italian nurses' cultural competence was acceptable, given
the growing diversity of the patient population, nurses should be better prepared
to face the changing health requests. CLINICAL RELEVANCE: Providing culturally
competent care has been associated with improved provider-client communication,
higher satisfaction with care, and health status improvement, as full
comprehension of health status, adherence to medications and lifestyle
recommendations, and appropriate utilization of the health system. Healthcare
providers need to be adequately trained to provide culturally competent care.
This research provides, for the first time, a report on Italian nurses' levels of
cultural competence, and strengthens the current literature underlining the need
for continuous education to enhance cultural competence among nurses.
PMID- 26444448
TI - Hormonal determinants of erectile dysfunction and lower urinary tract symptoms in
middle-aged and elderly men with prediabetes.
AB - OBJECTIVES: Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) are
common in diabetic men. The aim of this study was to investigate hormonal
determinants, the prevalence and severity of ED and LUTS in middle-aged and
elderly men with prediabetes (PD). METHODS: We investigated 176 men with PD and
184 healthy peers. PD was defined according American Diabetes Association. ED
according IIEF scale and LUTS according IPSS scale were assessed. Total
testosterone (TT), calculated free testosterone (cFT), dehydroepiandrosterone
sulfate (DHEAS) and insulin-like growth factor 1 (IGF-1) were measured. RESULTS:
The prevalence of ED in patients with PD was higher than in control group (30
versus 24%) as well as the prevalence and severity of ED and LUTS in elderly (60
80 years) and middle-aged (40-59 years) men with PD was higher than in healthy
peers. In middle-aged pre-diabetic men, the more severe LUTS symptoms were
associated with low TT and DHEAS, while in elderly men with low cFT and DHEAS.
The higher prevalence of ED in middle-aged men with PD was associated with cFT
and DHEAS, while in elderly pre-diabetic men with TT and IGF-1. CONCLUSIONS: The
prevalence and severity of LUTS and ED symptoms were higher in pre-diabetic men
than in healthy peers. Hormonal determinants of these symptoms are different in
middle-aged and elderly patients with PD.
PMID- 26444450
TI - Disease activity score in 28 joints at 3 months after the initiation of biologic
agent can be a predictive target for switching to the second biologic agent in
patients with polyarticular juvenile idiopathic arthritis.
AB - OBJECTIVE: To clarify polyarticular juvenile idiopathic arthritis (pJIA) patients
who failed to maintain prolonged remission with the first biologic agent.
METHODS: Fourteen pJIA patients were observed for 47.5 months (median) after
initiating the first biologic agent. RESULTS: Eight maintained sustained clinical
remission (median 47 months) with the first biologic agents, while the six
switched to the second one due to lack of efficacy, thereafter. Receiver
operating characteristic (ROC) analysis revealed that disease activity score in
28 joints (DAS28) of 2.37 at 3 months could distinguish between the two patient
groups (p = 0.001). CONCLUSION: pJIA patients with DAS28 >2.37 at 3 months of the
initial biologic therapy may be considered to switch to the second biologics.
PMID- 26444452
TI - Assessment of the Helical Ventricular Myocardial Band Using Standard
Echocardiography.
PMID- 26444453
TI - Reply: To PMID 24814570.
PMID- 26444454
TI - Reply: To PMID 24814570.
PMID- 26444456
TI - Epithelial sodium channel is involved in H2S-induced acute pulmonary edema.
AB - Acute pulmonary edema is one of the major outcomes of exposure to high levels of
hydrogen sulfide (H2S). However, the mechanisms involved in H2S-induced acute
pulmonary edema are still poorly understood. Therefore, the present study is
designed to evaluate the role of epithelial sodium channel (ENaC) in H2S-induced
acute pulmonary edema. The Sprague-Dawley rats were exposed to sublethal
concentrations of inhaled H2S, then the pulmonary histological and lung
epithelial cell injury were evaluated by hematoxylin-eosin staining and electron
microscopy, respectively. In addition to morphological investigation, our results
also revealed that H2S exposure significantly decreased the alveolar fluid
clearance and increased the lung tissue wet-dry ratio. These changes were
demonstrated to be associated with decreased ENaC expression. Furthermore, the
extracellular-regulated protein kinases 1/2 pathway was demonstrated to be
implicated in H2S-mediated ENaC expression, because PD98059, an ERK1/2
antagonist, significantly mitigated H2S-mediated ENaC down-regulation. Therefore,
our results show that ENaC might represent a novel pharmacological target for the
treatment of acute pulmonary edema induced by H2S and other hazardous gases.
PMID- 26444457
TI - The influence of prostatic anatomy and neurotrophins on basal prostate epithelial
progenitor cells.
AB - BACKGROUND: Based on findings of surface marker, protein screens as well as the
postulated near-urethral location of the prostate stem cell niche, we were
interested whether androgen ablation, distinct anatomic regions within the
prostate or neurotrophins have an influence on basal prostate epithelial
progenitor cells (PESCs). METHODS: Microdissection of the prostate, enzymatic
digestion, and preparation of single cells was performed from murine and human
prostates. Adult PESC marker expressions were compared between a group of C57BL/6
mice and a separate group of castrated C57BL/6 mice. Surface markers CD13/CD271
on human prostate epithelial progenitor cells were evaluated by FACS analyses in
cells cultured under novel stem cell conditions. The effect of neurotrophins NGF,
NT3, and BDNF were evaluated with respect to their influence on proliferation and
activation of human basal PESCs in vitro. RESULTS: We demonstrate the highest
percentage of CD49f+ and Trop2+ expressing cells in the urethra near prostatic
regions of WT mice (Trop2+ proximal: 10% vs. distal to the urethra: 3%, P <
0.001). While a marked increase of Trop2 expressing cells can be measured both in
the proximal and distal prostatic regions after castration, the most prominent
increase in Trop2+ cells can be measured in the prostatic tissue distant to the
urethra. Furthermore, we demonstrate that the proportion of syndecan-1 expressing
cells greatly increases in the regions proximal to the urethra after castration
(WT: 5% vs. castrated: 40%). We identified heterogeneous CD13 and nerve growth
factor receptor (p75(NGFR), CD271) expression on CD49f(+)/TROP2(high) human basal
PESCs. Addition of the neurotrophins NT3, BDNF, and NGF to the stem cell media
led to a marked temporary increase in the proliferation of human basal PESCs.
CONCLUSIONS: Our results in mice support the model, in which the proximal
urethral region contains the prostate stem cell niche while a stronger androgen
dependent regulation of adult prostate stem cells can be found in the peripheral
prostatic tissue. Neutrophin signaling via nerve growth factor receptor is
possibly involved in human prostate stem cell homeostasis.
PMID- 26444458
TI - The Cutaneous, Net Clinical, and Health Economic Benefits of Advanced Pneumatic
Compression Devices in Patients With Lymphedema.
AB - IMPORTANCE: The prevalence and clinical burden of lymphedema is known to be
increasing. Nevertheless, evidence-based comparative effectiveness data regarding
lymphedema therapeutic interventions have been poor. OBJECTIVE: To examine the
impact of an advanced pneumatic compression device (APCD) on cutaneous and other
clinical outcomes and health economic costs in a representative privately insured
population of lymphedema patients. DESIGN, SETTING, AND PARTICIPANTS:
Retrospective analysis of a deidentified private insurance database from 2007
through 2013, and multivariate regression analysis comparing outcomes for the 12
months before and after APCD purchase, adjusting for baseline patient
characteristics. Patients with lymphedema who received an APCD who were
commercially insured and Medicare managed care enrollees from a large, national
US managed care health insurer. The study population was evaluated as cancer
related and non-cancer-related lymphedema cohorts. INTERVENTION: Receipt of an
APCD. MAIN OUTCOMES AND MEASURES: Rates of cellulitis, use of lymphedema-related
manual therapy, outpatient hospital visits, and inpatient hospitalizations.
Lymphedema-related direct costs were measured for home health care, hospital
outpatient care, office visits, emergency department use, and inpatient care.
RESULTS: The study sample included 718 patients (374 in the cancer cohort and 344
in the noncancer cohort). In both cohorts, use of an APCD was associated with
similar reductions in adjusted rates of cellulitis episodes (from 21.1% to 4.5%
in the cancer cohort and 28.8% to 7.3% in the noncancer cohort; P < .001 for
both), lymphedema-related manual therapy (from 35.6% to 24.9%in the cancer cohort
and 32.3% to 21.2% in the noncancer cohort; P < .001 for both), and outpatient
visits (from 58.6% to 41.4% in the cancer cohort and 52.6% to 31.4% in the
noncancer cohort; P < .001 for both). Among the cancer cohort, total lymphedema
related costs per patient, excluding medical equipment costs, were reduced by 37%
(from $2597 to $1642, P = .002). The corresponding decline in costs for the
noncancer cohort was 36% (from $2937 to $1883, P = .007). CONCLUSIONS AND
RELEVANCE: The study found an association between significant reductions in
episodes of cellulitis (cancer vs noncancer cohorts) and outpatient care and
costs of APCD acquisition within a 1-year time frame in patients with both cancer
related and non-cancer-related lymphedema.
PMID- 26444459
TI - A Review of HIV in Baltimore, Maryland, USA.
PMID- 26444460
TI - Specialty Pharmaceuticals for Hyperlipidemia--Impact on Insurance Premiums.
PMID- 26444461
TI - Post-Vietnam Dioxin Exposure in Agent Orange-Contaminated C-123 Aircraft.
PMID- 26444462
TI - The Interwar Period: Is There a Plan for Sustainment of Essential Skills?
PMID- 26444463
TI - Palliative Care in the U.S. Military Health System.
PMID- 26444464
TI - Veterans Health Administration's MOVE! Weight Management Program: Primary Care
Clinicians' Perceptions of Program Implementation.
AB - The Veterans Health Administration's MOVE! Program is the largest health care
delivered weight loss intervention in the United States. As a referring
clinician's perceptions and knowledge of health programs may impact
implementation, examining perceptions of MOVE! may inform improvements to this
and other programs. This study investigated primary care clinician perceptions of
MOVE! (n = 754, 50% nurses). Perceived effectiveness ratings were highest for
groups with 11 to 25 group members (p < 0.01) and for a combined lecture and
support group format (p = 0.026), though session length and several other aspects
of delivery were not associated with perceptions of effectiveness. MOVE! staff
also rated the program as more effective than did other clinicians (p < 0.01).
Many respondents lacked knowledge about program specifics, especially those not
involved with MOVE! delivery (vs. those directly involved; p < 0.01). These
findings indicate that variety in group size and format is related to perceptions
of MOVE! effectiveness. Also, clinicians not involved with MOVE! may lack
knowledge about the program and underestimate its effectiveness, which could
negatively affect referral likelihood or enthusiasm expressed to referred
patients. Findings highlight opportunities for clarifying perceptions of a weight
control program among clinicians in a large health care system.
PMID- 26444465
TI - Health and Health Care Service Utilization Among U.S. Veterans Denied VA Service
Connected Disability Compensation: A Review of the Literature.
AB - The general consensus in studies of individuals seeking federal disability
compensation is that individuals "denied" disability compensation are healthier
than those "awarded." In contrast, studies of military veterans seeking U.S.
Department of Veterans Affairs (VA) disability compensation suggest that those
"denied" ("denied applicants") may be as impaired as those "awarded" ("awarded
applicants"), and likely have critical, albeit unmet health care needs. Moreover,
although social isolation among U.S. Veterans has received some attention, its
broad influence on health and health care consumption among veterans "denied" VA
disability compensation is not well understood. OBJECTIVES: To provide a more
thorough understanding of "denied" applicants' health, health care utilization,
and social conditions. METHODS: We reviewed published reports of health, health
care utilization, and social isolation "relevant" to U.S. Veterans "denied" VA
disability compensation. Among 122 research items initially reviewed, a total of
47 met our inclusion criteria and are summarized herein. RESULTS: Compared to
veterans "awarded" VA disability compensation, those "denied" have poorer health,
use less VA health care, and may experience social isolation. CONCLUSIONS:
Veterans "denied" VA disability compensation may comprise a vulnerable subgroup
of veterans in need of supportive services. Such needs may be addressed through
evidence-based targeted outreach programs.
PMID- 26444467
TI - Army Active Duty Members' Linkage to Veterans Health Administration Services
After Deployments to Iraq or Afghanistan and Following Separation.
AB - This study described the rate and predictors of Operation Enduring
Freedom/Operation Iraqi Freedom active duty Army members' enrollment in and use
of Veterans Health Administration (VHA) services (linkage), as well as variation
in linkage rates by VHA facility. We used a multivariate mixed effect regression
model to predict linkage to VHA, and also calculated linkage rates in the
catchment areas of each facility (n = 158). The sample included 151,122 active
duty members who deployed to Iraq or Afghanistan and then separated from the Army
between fiscal years 2008 and 2012. Approximately 48% of the active duty members
separating utilized VHA as an enrollee within one year. There was significant
variation in linkage rates by VHA facilities (31-72%). The most notable variables
associated with greater linkage included probable serious injury during index
deployment (odds ratio = 1.81), separation because of disability (odds ratio =
2.86), and various measures of receipt of VHA care before and after separation.
Information about the individual characteristics that predict greater or lesser
linkage to VHA services can be used to improve delivery of health care services
at VHA as well as outreach efforts to active duty Army members.
PMID- 26444466
TI - Mental Health Treatment Among Soldiers With Current Mental Disorders in the Army
Study to Assess Risk and Resilience in Service Members (Army STARRS).
AB - A representative sample of 5,428 nondeployed Regular Army soldiers completed a
self-administered questionnaire (SAQ) and consented to linking SAQ data with
administrative records as part of the Army Study to Assess Risk and Resilience in
Service members. The SAQ included information about prevalence and treatment of
mental disorders among respondents with current Diagnostic and Statistical Manual
of Mental Disorders, Fourth Edition (DSM-IV) internalizing (anxiety, mood) and
externalizing (disruptive behavior, substance) disorders. 21.3% of soldiers with
any current disorder reported current treatment. Seven significant predictors of
being in treatment were identified. Four of these 7 were indicators of
psychopathology (bipolar disorder, panic disorder, post-traumatic stress
disorder, 8+ months duration of disorder). Two were sociodemographics (history of
marriage, not being non-Hispanic Black). The final predictor was history of
deployment. Treatment rates varied between 4.7 and 71.5% depending on how many
positive predictors the soldier had. The vast majority of soldiers had a low
number of these predictors. These results document that most nondeployed soldiers
with mental disorders are not in treatment and that untreated soldiers are not
concentrated in a particular segment of the population that might be targeted for
special outreach efforts. Analysis of modifiable barriers to treatment is needed
to help strengthen outreach efforts.
PMID- 26444468
TI - A Health Assessment Survey of Veteran Students: Utilizing a Community College
Veterans Affairs Medical Center Partnership.
AB - OBJECTIVE: To assess health status among student veterans at a community college
utilizing a partnership between a Veterans Affairs Medical Center and a community
college. PARTICIPANTS: Student veterans at Cuyahoga Community College in
Cleveland, Ohio, in January to April 2013. METHODS: A health assessment survey
was sent to 978 veteran students. Descriptive analyses to assess prevalence of
clinical diagnoses and health behaviors were performed. Logistic regression
analyses were performed to assess for independent predictors of functional
limitations. RESULTS: 204 students participated in the survey (21% response
rate). Self-reported depression and unhealthy behaviors were high. Physical and
emotional limitations (45% and 35%, respectively), and pain interfering with work
(42%) were reported. Logistic regression analyses confirmed the independent
association of self-reported depression with functional limitation (odds ratio
[OR] = 3.3, 95% confidence interval [CI] 1.4-7.8, p < 0.05, and C statistic 0.72)
and of post-traumatic stress disorder with pain interfering with work (OR 3.9, CI
1.1-13.6, p < 0.05, and C statistic 0.75). CONCLUSION: A health assessment survey
identified priority areas to inform targeted health promotion for student
veterans at a community college. A partnership between a Veterans Affairs Medical
Center and a community college can be utilized to help understand the health
needs of veteran students.
PMID- 26444469
TI - Impact of Childhood Abuse on Physical and Mental Health Status and Health Care
Utilization Among Female Veterans.
AB - OBJECTIVE: To determine whether childhood abuse predicts health symptoms and
health care use among female veterans. METHODS: Participants were 369 female
patients at Veterans Affairs hospitals in New England who completed a mail
survey. Multiple regression analyses were conducted to determine the differential
impact of childhood physical abuse and childhood sexual abuse on health symptoms
and health care use, while accounting for age, race, military branch, and
military sexual trauma (MST). RESULTS: In our sample, 109 (29%) female veterans
reported experiencing childhood abuse. After adjusting for age, race, military
branch, childhood sexual abuse, and MST, childhood physical abuse was predictive
of poorer physical health, and greater depressive and post-traumatic stress
disorder symptoms. No significant association was found between childhood sexual
abuse and poor physical or mental health status. After adjusting for other
factors, childhood physical abuse was associated with more frequent use of
medical health care. Childhood sexual abuse was not a predictor for health care
use. CONCLUSIONS: Childhood physical abuse remains an important contributor to
physical health and mental health, even after adjusting for the more proximate
experience of MST. Screening for adverse childhood experiences may facilitate
access to appropriate physical and mental health treatment among female veterans.
PMID- 26444470
TI - Humanitarian Surgical Care Provided by a French Forward Surgical Team: Ten Years
of Providing Medical Support to the Population of the Ivory Coast.
AB - INTRODUCTION: The aims of this study were as follows: first to quantify and
review the types of surgical procedures performed by military surgeons assigned
to a Forward Surgical Team (FST) providing medical support to the population
(MSP) in the Ivory Coast (IC), and second to analyze how this MSP was achieved.
METHODS: Between 2002 and 2012, all of the local nationals operated on by the
different FSTs deployed in the IC were included in the study. The surgical
activity was analyzed and divided into surgical specialties, war wounds, nonwar
emergency trauma, nontrauma emergencies, and elective surgery. Demographics,
circumstances of health care management, wounded organs, and types of surgical
procedures were described. RESULTS: Over this period, surgeons operated on 2,315
patients and performed 2,556 procedures. Elective surgery accounted for 78.7% of
the surgical activity, nontrauma emergencies accounted for 12.7%, nonwar
emergency trauma accounted for 8%, and war wounds accounted for 0.6%. The main
surgical activities were visceral (43.8%) and orthopedic (including soft tissues)
surgeries (38.5%). CONCLUSION: The FSTs contributed widely to MSP in the IC. This
MSP required limited resources, standardization of the procedures and specific
skills beyond the original surgical specialties of military surgeons to fulfill
the needs of the local population.
PMID- 26444471
TI - Falls in a Young Active Amputee Population: A Frequent Cause of
Rehospitalization?
AB - Falls occur in up to 50% of amputees within a single year of their operation and
up to 40% of these falls result in injury. However, there is a lack of data
evaluating falls in a young, active amputee population despite an estimated 58%
of persons living with an amputation being under the age of 65. The authors
evaluated an amputee population (n = 393) with a mean age of 25.53 years. Overall
incidence, prevalence, fall characteristics, and risk factors were calculated for
falls resulting in rehospitalization. An incidence of 1.92 per 1,000 person years
with a prevalence of 2.04% was found with 87.5% occurring within the first 6
months following definitive amputation. Of the patients rehospitalized, 75%
required at least 1 surgical procedure. Infectious complications had the most
significant morbidity requiring a mean of 5 operative procedures. Those that
delayed evaluation (mean = 13 days) vs. those that presented 0 to 1 day from a
fall were significantly more at risk of an infectious complication (p = 0.03).
This study is the first to report such a relationship, and emphasizes the need
for at-risk patients to seek early medical attention as this may minimize the
risk of infection and obviate the need for surgical intervention.
PMID- 26444472
TI - The Use of Intravenous Tranexamic Acid in Patients Undergoing Total Hip or Knee
Arthroplasty: A Retrospective Analysis at a Single Military Institution.
AB - OBJECTIVE: To describe a single institution's experience after initiation of a
protocol in which all primary total hip arthroplasty (THA) and total knee
arthroplasty (TKA) patients were administered intravenous tranexamic acid (TXA)
intraoperatively to decrease perioperative blood loss. METHODS: A retrospective
review of medical records at a single institution from February 2012 to April
2014. The TXA treatment group was compared to a control group. We reviewed
intraoperative blood loss, preoperative hemoglobin (Hb) levels, postoperative day
0 to 2 Hb levels, transfusion rates, postoperative venous thromboembolism, and
other complication rates. RESULTS: 259 patients underwent either TKA (165) or THA
(94). 121 received perioperative intravenous TXA and 138 did not. There was a
statistically decreased rate of allogeneic blood transfusion (0 vs. 10, p =
0.003) as well as a higher postoperative day 2 Hb level (10.8 +/- 1.1 vs. 10.2 +/
2.6 g/dL, p = 0.02) in the treatment group. There was no statistical difference
in any variable measured in the THA group, though there was a trend toward higher
postoperative Hb levels at all-time points measured. CONCLUSION: Intravenous TXA
is a safe and effective drug to decrease perioperative blood loss and allogeneic
transfusion in THA and TKA. There was no increased risk of venous thromboembolism
or other complications in our review.
PMID- 26444473
TI - Impact of a Diabetes Risk Score on Lifestyle Education and Patient Adherence
(IDEA) in Prediabetes: A Multisite Randomized Controlled Trial.
AB - BACKGROUND: To evaluate whether knowledge of a personalized Diabetes Risk Score
(DRS) improved performance in a 12-week lifestyle change program for prediabetes.
METHODS: Randomized subjects at four clinics provided samples for a DRS at
baseline, 12, and 24 weeks. The intervention group received scores at each point,
whereas the control group only received this information at 12 and 24 weeks.
Outcomes included attendance and changes in weight, abdominal circumference,
blood pressure, fasting glucose, hemoglobin A1c, cholesterol, and risk score.
RESULTS: Baseline characteristics were similar in the groups (n = 192) and within
risk-stratified subgroups. At 12 weeks, there were no differences in outcomes,
with mean weight loss of 4.61 kg in the intervention group and 4.43 kg in the
control group (p = 0.79). Both groups were given 12-week risk scores, with
previously unseen baseline scores for the control group. The control group
continued to lose additional weight (1.21 kg) by 24 weeks, whereas the
intervention group regained previously lost weight (0.33 kg) (p = 0.04).
CONCLUSIONS: The knowledge of a single baseline personalized DRS did not affect
performance in a lifestyle modification program. However, the knowledge of an
improvement in risk score, and the timing of this information, may impact further
adherence.
PMID- 26444474
TI - Effectiveness of a Dental Unit Waterline Treatment Protocol With A-Dec ICX and
Citrisil Disinfectants.
AB - This study evaluated the effectiveness of a Dental Unit Waterline disinfection
protocol utilizing two waterline disinfectant tablets in a dental treatment
clinic. The water effluent from 47 dental treatment units was sampled to
determine bacterial load. Four dental treatment units were shocked with the
multivalent Sterilex Ultra liquid biocide, followed by a 5-week course of routine
disinfection using either the A-dec ICX or Citrisil effervescing tablets. Aseptic
samples were taken twice weekly, and bacterial load was determined. No
significant difference was found when comparing A-dec ICX with Citrisil, but a
significant difference was seen between the use of either tablet and no tablet.
In addition, a survey was conducted to evaluate the effect of user compliance on
infection control. The results indicate that proper training, coupled with the
use of appropriate disinfectants and shock treatment, are important aspects of
maintaining low bacterial burden in dental water lines.
PMID- 26444475
TI - "Angels in Army Drab": The Medical Specialists Corps and COL Emma Vogel.
PMID- 26444476
TI - Neurotherapy of Traumatic Brain Injury/Post-Traumatic Stress Symptoms in Vietnam
Veterans.
AB - Previous report suggested the beneficial effects of an adaptation of the Flexyx
Neurotherapy System (FNS) for the amelioration of mixed traumatic brain
injury/post-traumatic stress symptoms in veterans of the Afghanistan and Iraq
wars. As a novel variant of electroencephalograph biofeedback, FNS falls within
the bioenergy domain of complementary and alternative medicine. Rather than
learning voluntary control over the production/inhibition of brain wave patterns,
FNS involves offsetting stimulation of brain wave activity by means of an
external energy source, specifically, the conduction of electromagnetic energy
stimulation via the connecting electroencephalograph cables. Essentially, these
procedures subliminally induce strategic distortion of ongoing brain wave
activity to presumably facilitate resetting of more adaptive patterns of
activity. Reported herein are two cases of Vietnam veterans with mixed traumatic
brain injury/post-traumatic stress symptoms, each treated with FNS for 25
sessions. Comparisons of pre- and post-treatment questionnaire assessments
revealed notable decreases for all symptoms, suggesting improvements across the
broad domains of cognition, pain, sleep, fatigue, and mood/emotion, including
post-traumatic stress symptoms, as well as for overall activity levels. Findings
suggest FNS treatment may be of potential benefit for the partial amelioration of
symptoms, even in some individuals for whom symptoms have been present for
decades.
PMID- 26444477
TI - Surgical Management of Symptomatic Extensor Digitorum Brevis Manus: A Proposed
Algorithm for Treatment.
AB - First described in 1734, the extensor digitorum brevis manus (EDBM) is an
anomalous extensor muscle found in the dorsum of the wrist and hand. Extensor
muscle variants of the hand are not uncommon, and EDBM has an estimated reported
incidence of approximately 2%. Although few extensor muscle variants become
clinically significant, there is a paucity of literature discussing these
anatomic variants, with most reports arising from cadaveric studies or isolated
case series. Similarly, there are few established indications for surgical
treatment of EDBM. In this case report, we describe the successful treatment of a
young patient with persistently symptomatic anomalous extensor tendon with
surgical excision and propose an algorithm for management after failure of
conservative measures.
PMID- 26444478
TI - Percutaneous Drainage of a Rapidly Enlarging Simple Ovarian Cyst in the Third
Trimester.
AB - BACKGROUND: Persistent adnexal masses increase the risk of pregnancy
complications including cyst rupture, ovarian torsion, and labor obstruction.
Treatment options include observation, surgical excision, and early first or
second trimester drainage. Our case represents the most advanced gestational age
for intervention with percutaneous drainage. CASE: A 32-year old G3P1102 at 29.2
weeks gestation presented with left lower quadrant pressure, right abdominal
fullness, and left uterine displacement. She had a right, simple-appearing
ovarian cyst, which had increased in size from previous ultrasounds to 12.8 *
13.4 * 15.7 cm. Ultrasound-guided percutaneous drainage with pigtail catheter
placement removed 1.2 L serous green fluid. Fluid culture was negative and
cytology showed no evidence of malignancy. The pigtail catheter was removed at
31.2 weeks because of pain at the surgical site and significant cyst regression.
The cyst resolved and she delivered via uncomplicated vaginal delivery at term.
CONCLUSION: A few case reports describe first and second trimester percutaneous
or transvaginal drainage of symptomatic ovarian cysts as a less invasive approach
than surgical excision. However, our case suggests drainage of a simple-appearing
cyst as an alternative treatment option in the third trimester when the risk of
preterm labor and fetal complications with surgical intervention is at its
highest.
PMID- 26444479
TI - Immunocompetent, Immunized Male With Mumps, Complicated by Orchitis and
Meningitis.
AB - Mumps is a rare pathology often not encountered in the emergency department
setting. It is an especially unusual finding in a fully immunized individual. We
present a case of a 26-year-old Army active duty male who was evaluated in the
emergency department for mumps over the course of two visits. The military
population is presumed fully immunized and immunocompetent, travels widely and
often lives in close quarters. This case highlights the importance for providers
to consider such a disease that carries a risk of significant morbidity, and
rarely, mortality. A literature review was performed evaluating mumps in the
vaccinated population.
PMID- 26444480
TI - Fluticasone as Treatment for Cluster Headaches in a Navy Aircrew Member.
AB - Cluster headaches (CHs) are one of the most debilitating of all the identified
headache syndromes. Their pathogenesis is poorly understood, which has made their
treatment challenging. Various medicines and modalities have been put forth in an
effort to minimize the symptoms, but none have proven to be consistently
reliable. For the active duty military aviator with CHs, this is further
compounded by the administrative restrictions to use many of those medications
secondary to their unwanted and potentially dangerous side effects. We present a
case of refractory CH in an active duty air crewman, treated with fluticasone,
which resulted in a remarkable reduction in symptoms allowing him to resume his
primary flight duties. We propose that fluticasone's effectiveness in improving
his CH symptoms stems from its anti-inflammatory properties.
PMID- 26444481
TI - A Case of Superior Mesenteric Artery Syndrome in a Healthy Active Duty Marine.
AB - Superior mesenteric artery (SMA) syndrome is an uncommon disorder that can lead
to small bowel obstructions or perforations. Typical populations include young
females with anorexia. However, there have been a few reports of healthy males
with acute vomiting reported to have SMA syndrome. Our case report highlights an
active duty Marine who developed SMA syndrome and the importance of recognizing
this disease given the severity in delay of diagnosis in population of young
healthy active duty members.
PMID- 26444482
TI - What to Do When the Inhaler Fails: Revisiting the Diagnosis.
AB - Paradoxical vocal fold movement is important to consider in the differential for
dyspnea on exertion or shortness of breath. It is often confused with asthma and
remains undiagnosed because of a paucity of pathognomonic examination and imaging
findings. This case serves as a reminder of the specific clinical picture,
diagnosis, and treatment of paradoxical vocal fold movement. It also highlights
the broader importance of continuity of care and the clinician's ability to
revisit the differential diagnosis if an initial workup is unrevealing or the
patient is not responding to treatment.
PMID- 26444483
TI - Manual Therapy for Chronic Low Back Pain in an F-5 Pilot.
AB - INTRODUCTION: Low back pain (LBP) in the aviator can be a significant safety risk
because of distraction during flight. Flight Surgeons are tasked with seeking out
appropriate medical care that reduces pilot risk while providing squadron
specific mission support. CASE: An F-5 pilot presented with chronic LBP seeking
nonpharmacological and noninvasive therapy. After 3 days of manual treatment that
corrected sacral, pelvic, and lumbar dysfunction, this pilot reported greater
than 80% reduction in overall pain and was able to return to flight. DISCUSSION:
Although underreported, a radiographic study and multiple case reports, identify
LBP as a significant problem among tactical air (tac air) pilots. As such, LBP
can become an in-flight distraction increasing the risk of a mishap. Benefits of
osteopathic manipulative therapy (OMT) as an adjunct to treatment of LBP in
civilian population were recently demonstrated. This case identified a tac air
pilot with chronic LBP that responded to three OMT sessions focused at the
sacrum, lumbar, and pelvis. CONCLUSION: The use of manual therapy in the form of
OMT significantly reduced this pilot's pain in three visits and maintained flight
status per aeromedical waiver guidelines.
PMID- 26444484
TI - Trichobezoars Detected and Treated Based on Plain Radiography.
AB - Bezoars are conglomerations of indigestible material that become trapped in the
gastrointestinal tract. We present a case of an 8-year-old female child diagnosed
with a gastric bezoar solely on plain radiography and treated with abdominal
surgical exploration and removal. In addition, traditional characteristic
radiographic findings and treatment options for bezoars found in the current
literature are reviewed.
PMID- 26444485
TI - Application of platelet/lymphocyte and neutrophil/lymphocyte ratios in early
diagnosis and prognostic prediction in patients with resectable gastric cancer.
AB - BACKGROUND: Gastric cancer is the fourth most frequent cancer and the second
cause of cancer-related deaths worldwide. China has a high incidence of gastric
cancer. Inflammation is a critical component of tumor progression. It has been
widely accepted that gastric cancer is an inflammation-driven cancer. In this
study, we investigated the application value of systemic inflammatory response
(SIR) markers, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte
ratio (NLR), in early diagnosis and prognostic prediction in patients with
resectable gastric cancer. MATERIALS AND METHODS: One hundred and sixty-two
patients with resectable gastric cancer were included and separated into groups
according to median pre-operative PLR or NLR values (PLR low: < 208 or PLR high:
>= 208, and NLR low: < 4.02 or NLR high: >= 4.02, respectively). To evaluate the
changes in PLR or NLR values after operation, we introduced the concept of
postpre-operative PLR or NLR ratios (< 1 indicated PLR or NLR values were
decreased after operation, while >= 1 suggested not decreased PLR or NLR values).
RESULTS: Pre-operative PLR and NLR levels were significantly higher in gastric
cancer patients compared with the healthy subjects. Low pre-operative PLR and NLR
levels correlated with better clinicopathological features, including decreased
depth of invasion, less lymph node metastasis and early tumor stage. Kaplan-Meier
plots illustrated that higher pre-operative NLR and PLR had decreased overall
survival (OS) and disease-free survival (DFS). Surgical tumor resection resulted
in a significant CONCLUSIONS: PLR and NLR measurements can provide important
diagnostic and prognostic results in patients with resectable gastric cancer.
PMID- 26444486
TI - Pyrolysis characteristics and pyrolysis products separation for recycling organic
materials from waste liquid crystal display panels.
AB - Waste liquid crystal display (LCD) panels mainly contain inorganic materials
(glass substrate with indium-tin oxide film), and organic materials (polarizing
film and liquid crystal). The organic materials should be removed beforehand
since the organic matters would hinder the indium recycling process. In the
present study, pyrolysis process is used to remove the organic materials and
recycle acetic as well as and triphenyl phosphate (TPP) from waste LCD panels in
an environmental friendly way. Several highlights of this study are summarized as
follows: (i) Pyrolysis characteristics and pyrolysis kinetics analysis are
conducted which is significant to get a better understanding of the pyrolysis
process. (ii) Optimum design is developed by applying Box-Behnken Design (BBD)
under response surface methodology (RSM) for engineering application which is
significant to guide the further industrial recycling process. The oil yield
could reach 70.53 wt% and the residue rate could reach 14.05 wt% when the
pyrolysis temperature is 570 degrees C, nitrogen flow rate is 6 L min(-1) and
the particle size is 0.5 mm. (iii) Furthermore, acetic acid and TPP are recycled,
and then separated by rotary evaporation, which could reduce the consumption of
fossil energy for producing acetic acid, and be reused in electronics
manufacturing industry.
PMID- 26444487
TI - Defect creation in metal-organic frameworks for rapid and controllable
decontamination of roxarsone from aqueous solution.
AB - Given the great harm to the human health of organic arsenic compounds (OACs),
developing highly efficient adsorbents with both rapid adsorption rate and high
saturation capacity is paramount important. Herein, Zr-based metal-organic
frameworks (MOFs) of UiO-66 have been successfully exploited for the efficient
decontamination of a typical organic arsenic compound of roxarsone (ROX) from
aqueous solution. The influences of the most significant parameters such as
contact time, adsorbate concentration, pH as well as ionic strength on the
adsorption of ROX were investigated. The amount of missing-linker defects in UiO
66 was systematically tuned by changing the concentration of modulator in the
reactants. The presence of the defects not only resulted in the dramatically
enhanced porosity, but also induced the creation of ZrOH groups which served as
the main active adsorption sites for efficient ROX sequestration. As a result,
adsorptive capacity of ROX over UiO-66 could be improved to 730 mg/g, which was
much higher than those of many reported adsorbents. Meanwhile, the adsorption
equilibrium time could be reduced to as short as 30 min. These merits, combined
with their excellent stability, prefigure the great potentials of these defect
tunable UiO-66 MOFs as adsorbents for the efficient removal of various OACs from
the polluted water.
PMID- 26444488
TI - Organic acids enhanced decoloration of azo dye in gas phase surface discharge
plasma system.
AB - A gas phase surface discharge plasma combined with organic acids system was
developed to enhance active species mass transfer and dye-containing wastewater
treatment efficacy, with Acid Orange II (AO7) as the model pollutant. The effects
of discharge voltage and various organic acid additives (acetic acid, lactic acid
and nonoic acid) on AO7 decoloration efficiency were evaluated. The experimental
results showed that an AO7 decoloration efficiency of approximately 69.0% was
obtained within 4 min of discharge plasma treatment without organic acid
addition, which was improved to 82.8%, 83.5% and 88.6% within the same treatment
time with the addition of acetic acid, lactic acid and nonoic acid, respectively.
The enhancement effects on AO7 decoloration efficiency could be attributed to the
decrease in aqueous surface tension, improvement in bubble distribution and
shape, and increase in ozone equivalent concentration. The AO7 wastewater was
biodegradable after discharge plasma treatment with the addition of organic acid.
AO7 decomposition intermediates were analyzed by UV-vis spectrometry and GC-MS; 2
naphthol, 1,4-benzoquinone, phthalic anhydride, coumarin, 1,2-naphthoquinone, and
2-formyl-benzoic acid were detected. A possible pathway for AO7 decomposition in
this system was proposed.
PMID- 26444489
TI - Risk assessment of persistent pharmaceuticals in biosolids: Dealing with
uncertainty.
AB - A screening-level risk assessment of biosolids-borne PPCPs in agricultural
scenarios was developed in this work. While several of these compounds are
efficiently removed in sewage treatment plants (STPs), others are recalcitrant to
degradation and can be found in sludge at significant levels. As the rate of
biosolids reuse for fertilising and/or amendment purposes is increasing, it is
necessary to evaluate the fate in soil and possible biotransfer of this type of
pollutants in the long-term. The study includes six compounds that were selected
considering data availability, presence in sludge and persistence. Due to the
scarce data still present in literature, a probabilistic assessment to address
uncertainty was developed. A 95th percentile of the hazard index (HI) exceeding 1
was obtained, with main contributions of triclosan and carbamazepine. Although
these estimates were obtained under a worst-case approach, and that they can vary
depending on scenario characteristics, they change the least-concern
classification associated to the presence of PPCPs in biosolids. A sensitivity
analysis indicates the high influence of application rate and sludge
concentration level on the results. Thus, the importance of developing new
strategies of removal in advanced STPs and the establishment of a specific
biosolids reuse regulation including this type of compounds acquires an added
significance.
PMID- 26444490
TI - Ligand Discovery for the Alanine-Serine-Cysteine Transporter (ASCT2, SLC1A5) from
Homology Modeling and Virtual Screening.
AB - The Alanine-Serine-Cysteine transporter ASCT2 (SLC1A5) is a membrane protein that
transports neutral amino acids into cells in exchange for outward movement of
intracellular amino acids. ASCT2 is highly expressed in peripheral tissues such
as the lung and intestines where it contributes to the homeostasis of
intracellular concentrations of neutral amino acids. ASCT2 also plays an
important role in the development of a variety of cancers such as melanoma by
transporting amino acid nutrients such as glutamine into the proliferating
tumors. Therefore, ASCT2 is a key drug target with potentially great
pharmacological importance. Here, we identify seven ASCT2 ligands by
computational modeling and experimental testing. In particular, we construct
homology models based on crystallographic structures of the aspartate transporter
GltPh in two different conformations. Optimization of the models' binding sites
for protein-ligand complementarity reveals new putative pockets that can be
targeted via structure-based drug design. Virtual screening of drugs,
metabolites, fragments-like, and lead-like molecules from the ZINC database,
followed by experimental testing of 14 top hits with functional measurements
using electrophysiological methods reveals seven ligands, including five
activators and two inhibitors. For example, aminooxetane-3-carboxylate is a more
efficient activator than any other known ASCT2 natural or unnatural substrate.
Furthermore, two of the hits inhibited ASCT2 mediated glutamine uptake and
proliferation of a melanoma cancer cell line. Our results improve our
understanding of how substrate specificity is determined in amino acid
transporters, as well as provide novel scaffolds for developing chemical tools
targeting ASCT2, an emerging therapeutic target for cancer and neurological
disorders.
PMID- 26444491
TI - A novel UHPLC method for the rapid and simultaneous determination of daidzein,
genistein and equol in human urine.
AB - This work reports on a novel method involving reverse-phased ultra-high
performance liquid chromatography (UHPLC) plus a spectrophotometric photodiode
array/fluorescence (FLR) detection system for determining the concentration of
equol and major soy isoflavones (daidzein and genistein) in human urine. The
proposed method was validated in terms of its linearity, sensitivity, accuracy
(recovery) and precision (intra- and inter-day repeatability). The isoflavone
profiles of urine samples from a group of menopausal women following oral soy
isoflavone supplementation were determined and compared. Screening for equol
producer status was accomplished with high sensitivity (detection limit of the
FLR detector 2.93nM). The method involves a short chromatographic run time
compared to conventional HPLC methods while allowing for the simultaneous and
reliable quantification of daidzein, genistein and equol in human urine. It also
allows for the rapid screening of multiple urine samples when testing for equol
production status and checking patient adherence to isoflavone treatment
regimens.
PMID- 26444492
TI - Structure and Biogenesis of Roussoellatide, a Dichlorinated Polyketide from the
Marine-Derived Fungus Roussoella sp. DLM33.
AB - The structure of the fungal metabolite roussoellatide (1) has been established by
spectroscopic and X-ray diffraction analyses. Results from feeding experiments
with [1-(13)C]acetate, [2-(13)C]acetate, and [1,2-(13)C]acetate were consistent
with a biosynthetic pathway to the unprecedented skeleton of 1 involving
Favorskii rearrangements in separate pentaketides, subsequently joined via an
intermolecular Diels-Alder reaction.
PMID- 26444493
TI - Long-term Cosmetic Alignment Following Surgery for Esotropia Versus Exotropia in
Childhood: A Comparison Using Survival Curves.
AB - PURPOSE: Although long-term results following repair of esotropia and exotropia
in childhood have been reported, the two entities have never been directly
compared. METHODS: Records of all children younger than 18 years who underwent
horizontal strabismus surgery from 2000 through 2012 were reviewed. Children with
structural eye pathology, severe vision loss, neurologic disorders, and
incomitant or combined horizontal and vertical deviations were excluded. Failure
was defined by a second horizontal surgery or a primary position deviation
greater than 20 prism diopters (PD) at any time during follow-up (as long as 10
years). A threshold of 20 PD was chosen because families often consider
deviations important enough to warrant a first or second surgery if it is larger
but not if it is smaller. RESULTS: Of 317 children, 235 with esotropia had
surgery at a mean age of 42 months and 82 with exotropia had surgery at a mean
age of 60 months. Overall, surgery was successful in 78% of those with esotropia
and 65% of those with exotropia. A second surgery was performed in 29 (12%) of
those with esotropia and 15 (18%) of those with exotropia. The mean deviation at
last follow-up, using absolute values, was 9 PD for esotropia and 10 PD for
exotropia. Survival curve success was better for esotropia (P = .008).
CONCLUSION: By survival curve analysis, success was more likely among children
with esotropia. Many "failures" slipped beyond the 20 PD threshold only
transiently and had deviations that were not noticeable to family or friends.
Overall, children did reasonably well long-term following surgery for both
esotropia and exotropia. Only 14% of the entire group required a second surgery
during an average of 41 months of follow-up.
PMID- 26444495
TI - Time evolution within a comoving window: scaling of signal fronts and
magnetization plateaus after a local quench in quantum spin chains.
AB - We present a modification of Matrix Product State time evolution to simulate the
propagation of signal fronts on infinite one-dimensional systems. We restrict the
calculation to a window moving along with a signal, which by the Lieb-Robinson
bound is contained within a light cone. Signal fronts can be studied unperturbed
and with high precision for much longer times than on finite systems.
Entanglement inside the window is naturally small, greatly lowering computational
effort. We investigate the time evolution of the transverse field Ising (TFI)
model and of the S = 1/2 XXZ antiferromagnet in their symmetry broken phases
after several different local quantum quenches. In both models, we observe
distinct magnetisation plateaus at the signal front for very large times,
resembling those previously observed for the particle density of tight binding
(TB) fermions. We show that the normalised difference to the magnetisation of the
ground state exhibits similar scaling behaviour as the density of TB fermions. In
the XXZ model there is an additional internal structure of the signal front due
to pairing, and wider plateaus with tight binding scaling exponents for the
normalised excess magnetisation. We also observe parameter dependent interaction
effects between individual plateaus, resulting in a slight spatial compression of
the plateau widths. In the TFI model, we additionally find that for an initial
Jordan-Wigner domain wall state, the complete time evolution of the normalised
excess longitudinal magnetisation agrees exactly with the particle density of TB
fermions.
PMID- 26444494
TI - An LSC epigenetic signature is largely mutation independent and implicates the
HOXA cluster in AML pathogenesis.
AB - Acute myeloid leukaemia (AML) is characterized by subpopulations of leukaemia
stem cells (LSCs) that are defined by their ability to engraft in immunodeficient
mice. Here we show an LSC DNA methylation signature, derived from xenografts and
integration with gene expression that is comprised of 71 genes and identifies a
key role for the HOXA cluster. Most of the genes are epigenetically regulated
independently of underlying mutations, although several are downstream targets of
epigenetic modifier genes mutated in AML. The LSC epigenetic signature is
associated with poor prognosis independent of known risk factors such as age and
cytogenetics. Analysis of early haematopoietic progenitors from normal
individuals reveals two distinct clusters of AML LSC resembling either lymphoid
primed multipotent progenitors or granulocyte/macrophage progenitors. These
results provide evidence for DNA methylation variation between AML LSCs and their
blast progeny, and identify epigenetically distinct subgroups of AML likely
reflecting the cell of origin.
PMID- 26444496
TI - Rapid, Regioconvergent, Solvent-Free Alkene Hydrosilylation with a Cobalt
Catalyst.
AB - Alkene hydrosilylation is typically performed with Pt catalysts, but inexpensive
base-metal catalysts would be preferred. We report a Co catalyst for anti
Markovnikov alkene hydrosilylation that can be used without added solvent at low
temperatures with low loadings, and can be generated in situ from an air-stable
precursor that is simple to synthesize from low-cost, commercially available
materials. In addition, a mixture of Co catalysts performs a tandem catalytic
alkene isomerization/hydrosilylation reaction that converts multiple isomers of
hexene to the same terminal product. This regioconvergent reaction uses
isomerization as a benefit rather than a hindrance.
PMID- 26444497
TI - Role of Fluorophore Charge on the In Vivo Optical Imaging Properties of Near
Infrared Cyanine Dye/Monoclonal Antibody Conjugates.
AB - Near-infrared (NIR) fluorophores have several advantages over visible-light
fluorophores, including superior light penetration in tissue and lower
autofluorescence. We recently demonstrated that a new class of NIR cyanine dyes
containing a novel C4'-O-alkyl linker exhibit greater chemical stability and
excellent optical properties relative to existing C4'-O-aryl variants. We
synthesized two NIR cyanine dyes with the same core structure but different
indolenine substituents: FNIR-774 bearing four sulfonate groups and FNIR-Z-759
bearing a combination of two sulfonates and two quaternary ammonium cations,
resulting in an anionic (-3) or monocationic (+1) charge, respectively. In this
study, we compare the in vitro and in vivo optical imaging properties of
monoclonal antibody (mAb) conjugates of FNIR-774 and FNIR-Z-759 with panitumumab
(pan) at antibody-to-dye ratios of 1:2 or 1:5. Conjugates of both dyes
demonstrated similar quenching capacity, stability, and brightness in target
cells in vitro. However, FNIR-Z-759 conjugates showed significantly lower
background in mice, resulting in higher tumor-to-background ratio. Thus, FNIR-Z
759 conjugates appear to have superior in vivo imaging characteristics compared
with FNIR-774 conjugates, especially in the abdominal region, regardless of the
dye-mAb ratio. These results suggest that zwitterionic cyanine dyes are a
promising class of fluorophores for improving in vivo optical imaging with
antibody-NIR dye conjugates.
PMID- 26444498
TI - Aromatic C-H Bond Functionalization Induced by Electrochemically in Situ
Generated Tris(p-bromophenyl)aminium Radical Cation: Cationic Chain Reactions of
Electron-Rich Aromatics with Enamides.
AB - An effective Friedel-Crafts alkylation reaction of electron-rich aromatics with N
vinylamides, induced by electrochemically in situ-generated TBPA radical cation,
has been developed; the resulting adducts are produced in good to excellent
yields. In the "ex-cell" type electrolysis, TBPA is transformed to its oxidized
form in situ and subsequently employed as an electron transfer reagent to
initiate a cationic chain reaction. An easily recoverable and reusable polymeric
ionic liquid-carbon black (PIL-CB) composite was also utilized as a supporting
electrolyte for the electrochemical generation of TBPA cation radical, without
sacrificing efficiency or stability after four electrolyses. Cyclic voltammetry
analysis and the results of control experiments demonstrate that the reaction of
electron-rich aromatics and N-vinylamides occurs via a cationic chain reaction,
which takes place though an oxidative activation of a C-H bond of electron-rich
aromatics instead of oxidation of the N-vinylamide as previously assumed.
PMID- 26444499
TI - Theoretical Investigation of Intramolecular Hydrogen Shift Reactions in 3
Methyltetrahydrofuran (3-MTHF) Oxidation.
AB - 3-Methyltetrahydrofuran (3-MTHF) is proposed to be a promising fuel component
among the cyclic oxygenated species. To have detailed insight of its combustion
kinetics, intramolecular hydrogen shift reactions for the ROO to QOOH reaction
class are studied for eight ROO isomers of 3-MTHF. Rate constants of all possible
reaction paths that involve formation of cyclic transition states are computed by
employing the CBS-QB3 composite method. A Pitzer-Gwinn-like approximation has
been applied for the internal rotations in reactants, products, and transition
states for the accurate treatment of hindered rotors. Calculated relative barrier
heights highlight that the most favorable reaction channel proceeds via a six
membered transition state, which is consistent with the computed rate constants.
Comparing total rate constants in ROO isomers of 3-MTHF with the corresponding
isomers of methylcyclopentane depicts faster kinetics in 3-MTHF than
methylcyclopentane reflecting the effect of ring oxygen on the intramolecular
hydrogen shift reactions.
PMID- 26444501
TI - Newsletter: President's Message.
PMID- 26444500
TI - The J-Curve in HIV: Low and Moderate Alcohol Intake Predicts Mortality but Not
the Occurrence of Major Cardiovascular Events.
AB - OBJECTIVES: In HIV-negative populations, light-to-moderate alcohol consumption is
associated with a lower cardiovascular morbidity and mortality than alcohol
abstention. Whether the same holds true for HIV-infected individuals has not been
evaluated in detail. DESIGN: Cohort study. METHODS: Adults on antiretroviral
therapy in the Swiss HIV Cohort Study with follow-up after August 2005 were
included. We categorized alcohol consumption into: abstention or very low (<1
g/d), low (1-9 g/d), moderate (10-29 g/d in women and 10-39 g/d in men), and high
alcohol intake. Cox proportional hazards models were used to describe the
association between alcohol consumption and cardiovascular disease-free survival
(combined endpoint), cardiovascular disease events (CADE) and overall survival.
Baseline and time-updated risk factors for CADE were included in the models.
RESULTS: Among 9741 individuals included, there were 788 events of major CADE or
death during 46,719 patient-years of follow-up, corresponding to an incidence of
1.69 events/100 person-years. Follow-up according to alcohol consumption level
was 51% no or very low, 20% low, 23% moderate, and 6% high intake. As compared
with no or very low alcohol intake, low (hazard ratio 0.79, 95% confidence
interval 0.63 to 0.98) and moderate alcohol intakes (0.78, 0.64 to 0.95) were
associated with a lower incidence of the combined endpoint. There was no
significant association between alcohol consumption and CADE. CONCLUSIONS:
Compared with no or very low alcohol consumption, low and moderate intake
associated with a better CADE-free survival. However, this result was mainly
driven by mortality and the specific impact of drinking patterns and type of
alcoholic beverage on this outcome remains to be determined.
PMID- 26444502
TI - Publish and Perish?
PMID- 26444503
TI - Letter to the Editor.
PMID- 26444504
TI - Letter to the Editor.
PMID- 26444505
TI - Point of Care Testing: Ensuring Accuracy.
PMID- 26444506
TI - A Critique of the Short Test of Functional Health Literacy in Adults.
AB - Effective healthcare relies on the ability to communicate with patients. Ninety
eight million Americans are estimated to have limited health literacy that can
impair their ability to read and interpret health-related education and
information. Low health literacy is associated with higher mortality and 30-day
hospital readmissions. Clinical nurse specialists and other advanced practice
nurses must be able to evaluate and select a health literacy assessment
instrument that is both reliable and produces valid data for the populations they
serve. To assist with this important decision-making process, the psychometric
properties of the Short Test of Functional Health Literacy in Adults are
critiqued in the following article.
PMID- 26444507
TI - Prescribing Sunshine: Evidence for Vitamin D Supplements.
PMID- 26444508
TI - beta-Adrenergic Blockers for Perioperative Cardiac Risk Reduction in People
Undergoing Vascular Surgery (Review).
PMID- 26444509
TI - Setting Motivation Into Motion.
PMID- 26444510
TI - Restraint Reduction, Restraint Elimination, and Best Practice: Role of the
Clinical Nurse Specialist in Patient Safety.
AB - PURPOSE: Baseline restraint prevalence for surgical step-down unit was 5.08%, and
for surgical intensive care unit, it was 25.93%, greater than the National
Database of Nursing Quality Indicators (NDNQI) mean. Project goal was sustained
restraint reduction below the NDNQI mean and maintaining patient safety.
BACKGROUND/RATIONALE: Soft wrist restraints are utilized for falls reduction and
preventing device removal but are not universally effective and may put patients
at risk of injury. Decreasing use of restrictive devices enhances patient safety
and decreases risk of injury. DESCRIPTION: Phase 1 consisted of advanced practice
nurse-facilitated restraint rounds on each restrained patient including
multidisciplinary assessment and critical thinking with bedside clinicians
including reevaluation for treatable causes of agitation and restraint
indications. Phase 2 evaluated less restrictive mitts, padded belts, and elbow
splint devices. Following a 4-month trial, phase 3 expanded the restraint
initiative including critical care requiring education and collaboration among
advanced practice nurses, physician team members, and nurse champions. EVALUATION
AND OUTCOMES: Phase 1 decreased surgical step-down unit restraint prevalence from
5.08% to 3.57%. Phase 2 decreased restraint prevalence from 3.57% to 1.67%, less
than the NDNQI mean. Phase 3 expansion in surgical intensive care units resulted
in wrist restraint prevalence from 18.19% to 7.12% within the first year,
maintained less than the NDNQI benchmarks while preserving patient safety.
INTERPRETATION/CONCLUSION: The initiative produced sustained reduction in
acute/critical care well below the NDNQI mean without corresponding increase in
patient medical device removal. IMPLICATIONS: By managing causes of agitation,
need for restraints is decreased, protecting patients from injury and increasing
patient satisfaction. Follow-up research may explore patient experiences with and
without restrictive device use.
PMID- 26444511
TI - Building a Unit-Level Mentored Program to Sustain a Culture of Inquiry for
Evidence-Based Practice.
AB - PURPOSE: This study tested the effectiveness of a dynamic educational and
mentoring program, facilitated by unit-level mentors, to introduce, promote, and
sustain an evidence-based practice (EBP) culture among nurses in a military
healthcare setting. BACKGROUND: The need to identify gaps in practice, apply
principles of EBP, and advance scientific applications in the pursuit of quality
nursing care is as important to military healthcare as it is in the civilian
sector. DESCRIPTION: The Advancing Research through Close Collaboration Model
guided the intervention and study. Three instruments were used: the
Organizational Readiness for System-wide Integration of Evidence-Based Practice,
EBP Beliefs, and EBP Implementation scales. The study took place in 3 military
hospitals simultaneously undergoing facility and staff integration. Data were
collected from staff nurses in the inpatient nursing units before and after a
facilitated education and mentoring intervention. OUTCOME: Three hundred sixty
nurses (38%) completed baseline, and 325 (31%) completed follow-up surveys.
Scores improved on all 3 measures following implementation of the program;
however, the differences were statistically significant only for the
Organizational Readiness for System-wide Integration of Evidence-Based Practice
scale (70.96 vs 77.63, t = -3.95, P < .01). In the paired individual
pretest/posttest subsample (n = 56), scores improved significantly on all 3
instruments. CONCLUSIONS: Despite typically high turnover rates of military
personnel and restructuring of 3 facilities during the study period, the
readiness for, beliefs about, and implementation of EBP improved. This study
suggests that a commitment to an EBP culture may diffuse among individuals in an
organization, even while experiencing significant change. It also demonstrates
that a unit-level mentored EBP program is sustainable despite changes in
organizational structure and workforce composition.
PMID- 26444512
TI - A Business Case Framework for Planning Clinical Nurse Specialist-Led
Interventions.
AB - PURPOSE: The purpose of this article is to describe a business case framework
that can guide clinical nurse specialists (CNS) in clinical intervention
development. BACKGROUND: Increased emphasis on cost-effective interventions in
healthcare requires skills in analyzing the need to make the business case,
especially for resource-intensive interventions. This framework assists the CNS
to anticipate resource use and then consider if the intervention makes good
business sense. BUSINESS CASE FRAMEWORK: We describe a business case framework
that can assist the CNS to fully explore the problem and determine if developing
an intervention is a good investment. We describe several analyses that
facilitate making the business case to include the following: problem
identification and alignment with strategic priorities, needs assessment,
stakeholder analysis, market analysis, intervention implementation planning,
financial analysis, and outcome evaluation. The findings from these analyses can
be used to develop a formal proposal to present to hospital leaders in a position
to make decisions. By aligning intervention planning with organizational
priorities and engaging patients in the process, interventions will be more
likely to be implemented in practice and produce robust outcomes. CONCLUSION: The
business case framework can be used to justify to organization decision makers
the need to invest resources in new interventions that will make a difference for
quality outcomes as well as the financial bottom line. This framework can be used
to plan interventions that align with organizational strategic priorities, plan
for associated costs and benefits, and outcome evaluation. IMPLICATIONS FOR CNS
PRACTICE: Clinical nurse specialists are well positioned to lead clinical
intervention projects that will improve the quality of patient care and be cost
effective. To do so requires skill development in making the business case.
PMID- 26444513
TI - Michael Verde's Memory Bridge: A Beacon of Hope for People Living With Dementia
and Those Who Care for Them.
PMID- 26444514
TI - Outcomes of Clinical Nurse Specialist Role Transformation to Population-Focused
Model.
AB - PURPOSE/OBJECTIVES: In 2010, our comprehensive cancer center developed a
professional practice model where the clinical nurse specialist role was
transformed to proactively plan and facilitate evidence-based best practices in
collaboration with a transdisciplinary, population-focused team that manages the
patient across the cancer care continuum. BACKGROUND: Prior to this transition,
practice was unit based, focused on nursing staff education, skills, and
competencies, and practice varied widely based on the needs of the unit. This
lack of role consistency resulted in decreased autonomy and collaboration and
frustration with not consistently impacting positive outcomes. DESCRIPTION:
Nursing leadership worked with the clinical nurse specialists to develop and
transition to a population-focused model. Some responsibilities in the unit-based
model were retained, whereas others were transitioned to different roles. The
reporting structure was centralized, and the role was realigned to focus on a
specific patient population encompassing care from diagnosis throughout
survivorship. OUTCOME: Baseline job satisfaction data were collected prior to the
transition and repeated at 6 and 12 months, then 2, 3, and 4 years after
implementation. Over time, there was significant improvement in participation in
decision making, support of leadership, and positive contributions to patients
and staff, resulting in improved nursing-sensitive patient outcomes, an increase
in evidence-based practice initiatives and nursing research projects, and
substantial professional growth of clinical staff. CONCLUSION: With this practice
model, clinical nurse specialists consistently and proactively plan and
facilitate evidence-based best practice in collaboration with a transdisciplinary
team that manages the patient from diagnosis through the cancer trajectory.
Results of outcome measurement report job satisfaction at an all-time high.
Significant impact is demonstrated for patients and families, the nursing staff,
and the organization. IMPLICATIONS: Healthcare organizations should evaluate
current roles and practice models for opportunities to incorporate innovations
that will result in improved patient care and satisfaction.
PMID- 26444516
TI - The Neutrophil-to-Lymphocyte Ratio Is Valuable at All Stages of Coronary Artery
Disease.
PMID- 26444517
TI - A Prospective Study of the Intra- and Postoperative Efficacy of Intraoperative
Neuromonitoring in Spinal Cord Stimulation.
AB - BACKGROUND: Accurate lead placement is critical for spinal cord stimulation (SCS)
efficacy. The traditional gold standard of awake placement is often technically
difficult. While there is retrospective evidence supporting the use of
intraoperative neurophysiological monitoring (IOM) as an alternative, a
prospective assessment has not yet been performed. OBJECTIVE: To prospectively
evaluate pain and functionality outcomes for IOM-guided SCS, validate two IOM
modalities as a means to lateralize lead placement and assess whether IOM can be
useful for postoperative programming. METHODS: A total of 73 patients were
implanted with SCS using electromyography (EMG) and somatosensory-evoked
potential collision studies (SSEP-CS) to verify lead placement. Patient pain and
function were assessed through serial administration of several validated
questionnaires. Stimulation parameters at 6 months were documented. RESULTS:
Statistically significant (p < 0.05) improvements were observed in the McGill
Pain Questionnaire, Oswestry Disability Index, Pain Catastrophizing Scale, and
Visual Analog Scale. EMG and SSEP-CS appropriately lateralized leads in 65/73
(89.0%) and 40/58 (69.0%) cases, respectively. EMG predicted active contacts in
use at follow-up with 82.7% sensitivity. CONCLUSIONS: We provide prospective
evidence that IOM can be used to verify SCS placement. Additionally, EMG may help
to streamline device programming and thereby improve outcomes by predicting the
ideal stimulation contacts in many cases.
PMID- 26444518
TI - Supported Lipid Bilayer Platform To Test Inhibitors of the Membrane Attack
Complex: Insights into Biomacromolecular Assembly and Regulation.
AB - Complement activation plays an important role in innate immune defense by
triggering formation of the membrane attack complex (MAC), which is a
biomacromolecular assembly that exhibits membrane-lytic activity against foreign
invaders including various pathogens and biomaterials. Understanding the details
of MAC structure and function has been the subject of extensive work involving
bulk liposome and erythrocyte assays. However, it is difficult to characterize
the mechanism of action of MAC inhibitor drug candidates using the conventional
assays. To address this issue, we employ a biomimetic supported lipid bilayer
platform to investigate how two MAC inhibitors, vitronectin and clusterin,
interfere with MAC assembly in a sequential addition format, as monitored by the
quartz crystal microbalance-dissipation (QCM-D) technique. Two experimental
strategies based on modular assembly were selected, precincubation of inhibitor
and C5b-7 complex before addition to the lipid bilayer or initial addition of
inhibitor followed by the C5b-7 complex. The findings indicate that vitronectin
inhibits membrane association of C5b-7 via a direct interaction with C5b-7 and
via competitive membrane association onto the supported lipid bilayer. On the
other hand, clusterin directly interacts with C5b-7 such that C5b-7 is still able
to bind to the lipid bilayer, and clusterin affects the subsequent binding of
other complement proteins involved in the MAC assembly. Taken together, the
findings in this study outline a biomimetic approach based on supported lipid
bilayers to explore the interactions between complement proteins and inhibitors,
thereby offering insight into MAC assembly and regulation.
PMID- 26444519
TI - Indoor Air Pollutant Exposure for Life Cycle Assessment: Regional Health Impact
Factors for Households.
AB - Human exposure to indoor pollutant concentrations is receiving increasing
interest in Life Cycle Assessment (LCA). We address this issue by incorporating
an indoor compartment into the USEtox model, as well as by providing recommended
parameter values for households in four different regions of the world differing
geographically, economically, and socially. With these parameter values, intake
fractions and comparative toxicity potentials for indoor emissions of dwellings
for different air tightness levels were calculated. The resulting intake
fractions for indoor exposure vary by 2 orders of magnitude, due to the
variability of ventilation rate, building occupation, and volume. To compare
health impacts as a result of indoor exposure with those from outdoor exposure,
the indoor exposure characterization factors determined with the modified USEtox
model were applied in a case study on cooking in non-OECD countries. This study
demonstrates the appropriateness and significance of integrating indoor
environments into LCA, which ensures a more holistic account of all exposure
environments and allows for a better accountability of health impacts. The model,
intake fractions, and characterization factors are made available for use in
standard LCA studies via www.usetox.org and in standard LCA software.
PMID- 26444520
TI - DETECTION OF CHOROIDAL FOLDS IN PATIENTS WITH VOGT-KOYANAGI-HARADA DISEASE BY
RETROMODE SCANNING LASER OPHTHALMOSCOPY.
AB - PURPOSE: To determine whether the choroidal folds in patients with Vogt-Koyanagi
Harada disease can be detected by retromode of a scanning laser ophthalmoscopy
(SLO) with infrared laser light source. METHODS: The authors examined two
patients with Vogt-Koyanagi-Harada disease at the acute stage by retromode
imaging scanning laser ophthalmoscopy with an infrared laser before and after
steroid treatment. RESULTS: The retromode imaging by scanning laser
ophthalmoscopy clearly and noninvasively delineated the choroidal folds in both
cases. The folds disappeared after steroid treatment and reappeared with
recurrences of uveitis. CONCLUSION: The retromode imaging by scanning laser
ophthalmoscopy can detect the choroidal folds and should be useful for detecting
and monitoring the choroidal folds in Vogt-Koyanagi-Harada disease.
PMID- 26444521
TI - ENDOGENOUS ENDOPHTHALMITIS CAUSED BY BRUCELLA MELITENSIS.
AB - PURPOSE: Brucella is an intracellular gram-negative pathogen that acts as a
facultative parasite. B. Melitensis endogenous endophthalmitis is quite rare. We
herein report an unusual case of B. melitensis endophthalmitis with a good
outcome after appropriate management. METHODS: A retrospective interventional
case report of an 18-year-old boy who had unexplained interrupted fever and
malaise for the past 4 months and was being treated as a case of fever of unknown
origin. He presented with a 10-day history of pain and loss of vision in the left
eye. Visual acuity in the left eye at time of presentation was counting fingers
near face. Extensive anterior chamber reaction and flare, as well as, vitritis
were found on examination. All blood and urine investigations and radiological
imaging were negative. RESULTS: A diagnostic/therapeutic vitrectomy with
antibiotic injection helped in identifying the offending organism and controlling
the inflammation. Vitrectomy sample revealed B. melitensis with no sensitive
result. Patient recovered vision in his eye to 20/150. Eye examination revealed a
quiet eye, with flat retina and some retinal pigment epithelial changes at
macula. CONCLUSION: B. melitensis endophthalmitis is a rarely encountered disease
entity. High suspicion and prompt management with vitrectomy and appropriate
antibiotic injection was successful in salvaging the patient's eye.
PMID- 26444522
TI - PSEUDO UVEAL MELANOMA CAUSED BY OPTIC DISK DRUSEN WITH JUXTAPAPILLARY CHOROIDAL
NEOVASCULAR MEMBRANE.
AB - PURPOSE: To describe two cases of choroidal hemorrhage caused by optic disk
drusen-induced choroidal neovascularization simulating uveal melanoma. METHODS:
Observational case reports of two patients and brief review of the literature.
RESULTS: Two patients were referred with pigmented juxtapapillary lesions
concerning for choroidal melanoma. Multimodal imaging revealed the presence of
optic disk drusen with overlying choroidal neovascular membranes and
peripapillary choroidal hemorrhage. Both patients were treated with antivascular
endothelial growth factor and the lesions resolved. CONCLUSION: In the setting of
diagnostic uncertainty, careful multimodal imaging can assist in distinguishing
between malignant choroidal melanoma and a benign simulating lesion. Optic disk
drusen with associated neovascularization and hemorrhage should be included in
the list of pseudomelanomas.
PMID- 26444523
TI - PIMASERTIB AND SEROUS RETINAL DETACHMENTS.
AB - PURPOSE: To report a case of multifocal serous retinal detachments associated
with pimasertib. METHODS: The authors report a 26-year-old patient who developed
bilateral multifocal serous retinal detachments appearing 2 days after starting
pimasertib (as part of a clinical trial investigating its use in low-grade
metastatic ovarian cancer) and rapidly resolving 3 days after stopping it.
CONCLUSION: The mechanism of MEK inhibitor induced visual toxicity remains
unclear. The pathophysiology of multifocal serous retinal detachments as a
complication of pimasertib is still poorly understood.
PMID- 26444526
TI - 2015 Eberhard F. Mammen Award Announcements: Part I--Most Popular Articles.
PMID- 26444525
TI - Suicidal ideation and suicide attempts among human immunodeficiency virus
infected adults: differences in risk factors and their implications.
AB - Many studies have investigated risk factors for suicidal ideation and suicide
attempt; however, most have failed to show differences in risk factors between
suicidal ideation and suicide attempt among the human immunodeficiency virus
(HIV)-infected population. This study was designed to identify differences in
risk factors between suicidal ideation and suicide attempts among HIV-infected
adults in Seoul. A face-to-face survey of 457 HIV-infected adults was conducted
by the Seoul Metropolitan Government in 2013. Multivariate logistic regression
analysis was used to identify factors associated with suicidal ideation and
suicide attempt. Among 422 participants, 44% had suicidal ideation, and 11% had
suicide attempts. The independent risk factors for suicidal ideation were young
and middle age, living with someone, history of AIDS-defining opportunistic
disease, history of treatment for depression, lower social support, and
psychological status. Beneficiaries of National Medical Aid, economic barriers to
treatment, history of treatment for depression, and lower psychological status
were independently associated with suicide attempts. Patients with HIV in Korea
were treated without cost in some centers. Thus, experiencing an economic barrier
to treatment might be due in part to ignorance of HIV care policies. Our findings
indicate that suicide attempts are associated with socioeconomic factors and
information inequality regarding medical care. In conclusion, suicidal ideation
closely associated with the psychosocial factors, whereas suicide attempt
demonstrates a stronger association with socioeconomic factors. Suicide
prevention measures should be implemented to provide information to help HIV
infected patients.
PMID- 26444527
TI - Tissue Factor in Arterial and Venous Thrombosis: From Pathophysiology to Clinical
Implications.
PMID- 26444529
TI - ?
PMID- 26444528
TI - Using the combined analysis of transcripts and metabolites to propose key genes
for differential terpene accumulation across two regions.
AB - BACKGROUND: Terpenes are of great interest to winemakers because of their
extremely low perception thresholds and pleasant floral odors. Even for the same
variety, terpene profile can be substantially different for grapevine growing
environments. Recently a series of genes required for terpene biosynthesis were
biochemically characterized in grape berries. However, the genes that dominate
the differential terpene accumulation of grape berries between regions have yet
to be identified. METHODS: Free and glycosidically-bound terpenes were identified
and quantified using gas chromatography-mass spectrometry (GC-MS) technique. The
transcription expression profiling of the genes was obtained by RNA sequencing
and part of the results were verified by quantitative real time PCR (QPCR). The
gene co-expression networks were constructed with the Cytoscape software v 2.8.2
( www.cytoscape.org). RESULTS: 'Muscat Blanc a Petits Grains' berries were
collected from two wine-producing regions with strikingly different climates,
Gaotai (GT) in Gansu Province and Changli (CL) in Hebei Province in China, at
four developmental stages for two consecutive years. GC-MS analysis demonstrated
that both free and glycosidically bound terpenes accumulated primarily after
veraison and that mature grape berries from CL contained significantly higher
concentrations of free and glycosidically bound terpenes than berries from GT.
Transcriptome analysis revealed that some key genes involved in terpene
biosynthesis were markedly up-regulated in the CL region. Particularly in the MEP
pathway, the expression of VviHDR (1-hydroxy-2-methyl-2-butenyl 4-diphosphate
reductase) paralleled with the accumulation of terpenes, which can promote the
flow of isopentenyl diphosphate (IPP) into the terpene synthetic pathway. The
glycosidically bound monoterpenes accumulated differentially along with
maturation in both regions, which is synchronous with the expression of a
monoterpene glucosyltransferase gene (VviUGT85A2L4 (VviGT14)). Other genes were
also found to be related to the differential accumulation of terpenes and
monoterpene glycosides in the grapes between regions. Transcription factors that
could regulate terpene synthesis were predicted through gene co-expression
network analysis. Additionally, the genes involved in abscisic acid (ABA) and
ethylene signal responses were expressed at high levels earlier in GT grapes than
in CL grapes. CONCLUSIONS: Differential production of free and glycosidically
bound terpenes in grape berries across GT and CL regions should be related at
least to the expression of both VviHDR and VviUGT85A2L4 (VviGT14). Considering
the expression patterns of both transcription factors and mature-related genes,
we infer that less rainfall and stronger sunshine in the GT region could initiate
the earlier expression of ripening-related genes and accelerate the berry
maturation, eventually limiting the production of terpene volatiles.
PMID- 26444531
TI - ?
PMID- 26444530
TI - ?
AB - Interethnic Analyses of Distributions in Children and Adolescents Mental
Disorders in a Health Care Utilization The study examines ethnic differences in
mental disorders in a child and adolescent psychiatry population in a major
German city from 2007 to 2011 (N = 5,680). Risks of developing specific mental
disorders were calculated. African migrant children and adolescents showed higher
risk in traumatic stress and adjustment disorders (F 43 in ICD-10), the Asiatic
group in dissociative disorders (F 44-45). Compared to other European migrants
the German children and adolescents without migration background had a higher
risk of affective disorders (F 3). Adolescents (N = 3,556) with Russian and
Polish background had a higher risk of disorders induced by psychotropic
substances (F 1). Turkish and Arabic adolescents had a 4- to 5-times increasing
risk in schizophrenia as well as schizotypal or delusional disorders (F 2). In
addition, mental disorders were influenced by gender and nationality. These study
results suggest that a different vulnerability to specific mental disorders is
associated to ethnicity.
PMID- 26444532
TI - ?
PMID- 26444533
TI - ?
PMID- 26444534
TI - ?
PMID- 26444535
TI - The Effect of Physicians' Treatment Recommendations on Their Epistemic Authority:
The Medical Expertise Bias.
AB - This study examines the hypothesis that patients perceive physicians who
recommend more active and major treatment as having greater epistemic authority.
The hypothesis is based on the assumption that patients expect that their
physicians should advocate for an active treatment rather than abstention from
treatment. The sample included 631 participants. Data were collected using a
between-subjects design and scenarios that described a person who suffers from a
medical problem and visits a physician (surgeon, orthopedist, or dentist). The
physician gives a passive or active recommendation regarding treatment. Different
levels of passive recommendation (against or wait on treatment) and active
recommendation (minor, moderate, or major procedures) were used. The experience
of the physician was also manipulated. The dependent measure was the patient's
rating of the physician's epistemic authority. Physicians who prescribed an
active mode of treatment were perceived as having a higher epistemic authority
than physicians who gave a passive recommendation. We named this phenomenon the
medical expertise bias, as people might be biased when judging the level of
expertise of their physicians such that those physicians who recommend an active
treatment are considered to have greater medical epistemic authority in general.
PMID- 26444536
TI - Evaluation of 563 children with chronic cough accompanied by a new clinical
algorithm.
AB - BACKGROUND: This study aims to evaluate the children with chronic cough and to
analyze their etiological factors according to the age groups. METHOD: Five
hundred sixty-three children with chronic cough were included. The last diagnosis
were established and were also emphasized according to the age groups. RESULTS:
The mean age was 5.4 +/- 3.8 years (2-months-17-years) and 52 % of them were
male. The most common final diagnosis from all the participants were: asthma
(24.9 %), asthma-like symptoms (19 %), protracted bacterial bronchitis (PBB)
(11.9 %), and upper airway cough syndrome (9.1 %). However, psychogenic cough was
the second most common diagnosis in the subjects over 6 years of age. CONCLUSION:
Asthma and asthma-like symptoms were the most common diagnosis in children.
Different age groups in children may have a different order of frequencies.
Psychogenic cough should be thought of in the common causes especially in older
children.
PMID- 26444538
TI - Erratum to: Single centre experience of the application of self navigated 3D
whole heart cardiovascular magnetic resonance for the assessment of cardiac
anatomy in congenital heart disease.
PMID- 26444537
TI - Evaluation of carbapenem resistance using phenotypic and genotypic techniques in
Enterobacteriaceae isolates.
AB - BACKGROUND: Bacterial resistance to antibiotics is increasing worldwide.
Antibiotic-resistant strains can lead to serious problems regarding treatment of
infection. Carbapenem antibiotics are the final treatment option for infections
caused by serious and life-threatening multidrug-resistant gram-negative
bacteria. Therefore, an understanding of carbapenem resistance is important for
infection control. In the study described herein, the phenotypic and genotypic
features of carbapenem-resistant Enterobacteriaceae strains isolated in our
hospital were evaluated. METHODS: In total, 43 carbapenem-resistant strains were
included in this study. Sensitivity to antibiotics was determined using the
VITEK((r))2 system. The modified Hodge test (MHT) and metallo-beta-lactamase
(MBL) antimicrobial gradient test were performed for phenotypic identification.
Resistance genes IMP, VIM, KPC, NDM-1, and OXA-48 were amplified by multiplex
PCR. RESULTS: The OXA-48 gene was detected in seven strains, and the NDM-1 gene
in one strain. No resistance genes were detected in the remainder of strains. A
significant correlation was observed between the MHT test and OXA-48 positivity,
and between the MBL antimicrobial gradient test and positivity for resistance
genes (p < 0.05). CONCLUSION: The finding of one NDM-1-positive isolate in this
study indicates that carbapenem resistance is spreading in Turkey. Carbapenem
resistance spreads rapidly and causes challenges in treatment, and results in
high mortality/morbidity rates. Therefore, is necessary to determine carbapenem
resistance in Enterobacteriaceae isolates and to take essential infection control
precautions to avoid spread of this resistance.
PMID- 26444540
TI - Inflammatory myofibroblastic tumour of the testis with confirmed anaplastic
lymphoma kinase gene rearrangement.
PMID- 26444539
TI - De novo transcriptome sequencing and comprehensive analysis of the drought
responsive genes in the desert plant Cynanchum komarovii.
AB - BACKGROUND: Cynanchum komarovii Al Iljinski is a xerophytic plant species widely
distributing in the severely adverse environment of the deserts in northwest
China. At present, the detailed transcriptomic and genomic data for C. komarovii
are still insufficient in public databases. RESULTS: To investigate changes of
drought-responsive genes and explore the mechanisms of drought tolerance in C.
komarovii, approximately 27.5 GB sequencing data were obtained using Illumina
sequencing technology. After de novo assembly 148,715 unigenes were generated
with an average length of 604 bp. Among these unigenes, 85,106 were annotated
with gene descriptions, conserved domains, gene ontology terms, and metabolic
pathways. The results showed that a great number of unigenes were significantly
affected by drought stress. We identified 3134 unigenes as reliable
differentially expressed genes (DEGs). During drought stress, the regulatory
genes were involved in signaling transduction pathways and in controlling the
expression of functional genes. Moreover, C. komarovii activated many functional
genes that directly protected against stress and improved tolerance to adapt
drought condition. Importantly, the DEGs were involved in biosynthesis, export,
and regulation of plant cuticle, suggesting that plant cuticle may play a vital
role in response to drought stress and the accumulation of cuticle may allow C.
komarovii to improve the tolerance to drought stress. CONCLUSION: This is the
first large-scale reference sequence data of C. komarovii, which enlarge the
genomic resources of this species. Our comprehensive transcriptome analysis will
provide a valuable resource for further investigation into the molecular
adaptation of desert plants under drought condition and facilitate the
exploration of drought-tolerant candidate genes.
PMID- 26444541
TI - Prevalence of fatigue in patients 3 months after stroke and association with
early motor activity: a prospective study comparing stroke patients with a
matched general population cohort.
AB - BACKGROUND: Fatigue is a common complaint after stroke. Reasons for higher
prevalence are still unclear. This study aimed to determine if fatigue prevalence
in stroke patients is different to that of age and gender matched general
population controls, and to explore whether early motor activity was associated
with reduced likelihood of fatigue three months after stroke. METHODS: This was a
prospective multicenter cohort study of stroke patients admitted to eleven
regional Norwegian hospitals, within 14 days after stroke. Stroke patients (n =
257) were age and gender matched to participants in a general population health
survey (HUNT3-survey) carried out in a regional county of central Norway. The
single-item fatigue questionnaire from the HUNT3-survey was administered to both
groups to compare prevalence. The association between early motor activity (time
in bed, time sitting out of bed, and time upright) and fatigue at three months
after stroke (Fatigue Severity Scale) was tested with logistic regression. Simple
models including each activity outcome, with adjustment for stroke severity and
pre-stroke function, were tested, as well as a comprehensive model that included
additional independent variables of depression, pain, pre-stroke fatigue, age and
gender. RESULTS: Prevalence was higher after stroke compared with the general
population: 31.1% versus 10.9%. In the simple regression models, none of the
early motor activity categories were associated with fatigue three months after
stroke. In the comprehensive model, depression, pain and pre-stroke fatigue were
significantly associated with post-stroke fatigue. Time in bed through the
daytime during hospital stay approached statistical significance (p = 0.058) with
an odds ratio for experiencing fatigue of 1.02 (95% CI 1.00-1.04) for each
additional 5.4 minutes in bed. CONCLUSIONS: Stroke patients had higher prevalence
of fatigue three months after stroke than the age and gender matched general
population sample, which may be partly explained by the stroke population being
in poorer health overall. The relationship between early motor activity (and
inactivity) and fatigue remains unclear. Further research, which may help drive
development of new treatments to target this challenging condition, is needed.
PMID- 26444542
TI - Production of serine protease inhibitors by mutagenesis and their effects on the
mortality of Aedes aegypti L. larvae.
AB - BACKGROUND: Dengue, transmitted primarily by the bites of infected Aedes aegypti
L., is transmitted to millions of individuals each year in tropical and
subtropical areas. Dengue control strategies are primarily based on controlling
the vector, using insecticides, but the appearance of resistance poses new
challenges. Recently, highly selective protease inhibitors by phage display were
obtained for digestive enzymes of the 4th instar larvae (L4) midgut. These
mutants were not confirmed as a larvicide due to the low yield of the expression
of these inhibitors. In the present study, chimera molecules were constructed
based on the mutations at positions P1-P4' selected previously. The T6, T23 and
T149 mutants were mixed with another Kunitz inhibitor, domain 1 of the inhibitor
boophilin (D1). METHODS: The chimeras T6/D1, T149/D1 and T23/D1 were expressed at
high levels in P. pastoris yeast, purified by ionic exchange chromatography and
their homogeneity was analyzed by SDS-PAGE. The chimera inhibitors were assayed
against larval trypsin, chymotrypsin and elastase using specific chromogenic
substrates. The inhibitors were assayed for their larvicide potential against L4.
RESULTS: The chimeras exhibited strong inhibitory activities against the larval
digestive enzymes in a dose-dependent manner. T6/D1, T149/D1 and T23/D1 exhibited
strong larvicidal activity against L4 of Ae. aegypti with inhibitor
concentrations in the MUM range. A synergistic increase in mortality was observed
when a mixture of the three chimeric inhibitors was tested. CONCLUSIONS: The
strategy for constructing the chimeric inhibitors was successful. The chimeras
showed strong larvicidal activity against Ae. aegypti. In the future, our
findings can be used to design synthetic inhibitors for larvae digestive enzymes
as an alternative method to control the dengue vector.
PMID- 26444543
TI - Ever dispense of prescribed allergy medication in children growing up close to
traffic: a registry-based birth cohort.
AB - BACKGROUND: Epidemiologic studies have shown conflicting results regarding the
role of traffic pollution in the development of allergic disease. This study
investigated the relationship between living close to traffic and ever dispense
of prescribed oral antihistamines or nasal anti-allergic medication, among young
children. The underlying aim was to investigate if children growing up close to
traffic pollution are at higher risk of developing allergy in early childhood.
METHODS: We investigated a birth cohort in southern Sweden, consisting of N = 26
128 children (0-6 years) with health outcome and exposure data. Of these
children, N = 7898, had additional covariate information. Traffic intensity and
yearly averages of dispersion-modeled concentrations of NOX (100 * 100 m grid) at
residential addresses, were linked with registry data on dispensed allergy
medication (the Swedish Prescribed Drug Register). Individual level covariate
information was obtained from questionnaires distributed to parents at Child
Health Care-center visits, eight months after birth. Cox proportional hazards
regression was used for the statistical analyses. RESULTS: Living in close
proximity to a road with equal to or greater than 8640 cars/day (compared to 0
8639 cars/day), was not associated with higher incidence of ever dispensed oral
antihistamine or nasal anti-allergic medication, with or without adjustment for
confounders (sex, breastfeeding, parental allergy, parental origin, season, and
year of birth). Similar results were found in relation to NOX. CONCLUSIONS:
Traffic-related exposure was not associated with higher incidence of ever
dispensed medication against allergy, in children 0-6 years in southern Sweden.
These results indicates that traffic-related exposure may not be a risk factor
for early onset allergy in children in southern Sweden. However, children with
dispense of prescribed allergy medication may be a selected subgroup, and the
results for this group may not be generalizable to all children with allergy.
PMID- 26444544
TI - A new high-throughput screening-compatible gap junctional intercellular
communication assay.
AB - BACKGROUND: Gap junctions (GJs) are intercellular channels through which
molecules smaller than 1 kDa can diffuse, and they have been suggested as drug
targets. To develop chemical drugs acting on this target, a high-throughput
screening (HTS) system for GJ modulators is necessary. RESULTS: We designed a
new, high-throughput GJ intercellular communication (GJIC) assay. This assay
system consisted of donor and acceptor cells from LN215 glioma cells that
expressed SLC26A4 and yellow fluorescent protein-H148Q/I152L (YFP(QL)),
respectively. The fluorescence of LN215-YFP(QL) acceptor cells, when cultured
alone, was not quenched by iodide. However when donor and acceptor cells, or
LN215-YFP(QL) and LN215-I(-) cells, were mixed and plated, they formed GJs. When
iodide was added, it was transported into donor cells by SLC26A4, diffused
through the GJs to acceptor cells, and quenched the YFP(QL) fluorescence. The
quenching rate was optimal at a 2:1 mixture of donor and acceptor cells. The
assay quality parameter, Z' factor, was calculated from data collected with
vehicle and carbenoxolone. For each assay, the Z' factor increased with time. The
Z' factor of a 10-s assay was 0.72 indicating that the assay quality was high
enough for use in HTS. This assay system also worked well in HOS osteosarcoma
cells with a Z' factor at 10 s of 0.70. CONCLUSIONS: We developed a new HTS
system for GJ modulators. The system had a high assay quality with a Z' factor >=
0.70, was rapid and required only 10 s per well, was inexpensive in requiring no
additional reagents, and was predicted to have a low rate of false-positive hits.
PMID- 26444545
TI - Erratum to: Establishing medical plausibility in the context of orphan medicines
designation in the European Union.
PMID- 26444546
TI - Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object
Exploration.
AB - To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in
learning, memory, and exploratory behavior in mice, a tissue-specific knockout of
BMPRII in the post-natal hippocampus and forebrain was generated. We found that
BMPRII mutant mice had normal spatial learning and memory in the Morris water
maze, but showed significantly reduced swimming speeds with increased floating
behavior. Further analysis using the Porsolt Swim Test to investigate behavioral
despair did not reveal any differences in immobility between mutants and
controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed
reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest
in object exploration. These results suggest that loss of BMPRII in the mouse
hippocampus and forebrain does not disrupt spatial learning and memory encoding,
but instead impacts exploratory and anxiety-related behaviors.
PMID- 26444547
TI - Endothelium Expression of Bcl-2 Is Essential for Normal and Pathological Ocular
Vascularization.
AB - Bcl-2 is an anti-apoptotic protein with important roles in vascular homeostasis
and angiogenesis. Mice globally lacking Bcl-2 (Bcl-2 -/-) are small in stature
and succumb to renal failure shortly after weaning as a result of renal
hypoplasia/cystic dysplasia. We have shown that Bcl-2 -/- mice displayed
attenuated retinal vascular development and neovascularization. In vitro studies
indicated that in addition to modulating apoptosis, Bcl-2 expression also impacts
endothelial and epithelial cell adhesion, migration and extracellular matrix
production. However, studies delineating the cell autonomous role Bcl-2
expression plays in the endothelium during vascular development, pruning and
remodeling, and neovascularization are lacking. Here we generated mice carrying a
conditional Bcl-2 allele (Bcl-2Flox/Flox) and VE-cadherin-cre (Bcl-2EC mice). Bcl
2EC mice were of normal stature and lifespan and displayed some but not all of
the retinal vascular defects previously observed in global Bcl-2 deficient mice.
Bcl-2EC mice had decreased numbers of endothelial cells, decreased retinal
arteries and premature primary branching of the retinal vasculature, but unlike
the global knockout mice, spreading of the retinal superficial vascular layer
proceeded normally. Choroidal neovascularization was attenuated in Bcl-2EC mice,
although retinal neovascularization accompanying oxygen-induced ischemic
retinopathy was not. Thus, Bcl-2 expression in the endothelium plays a
significant role during postnatal retinal vascularization, and pathological
choroidal but not retinal neovascularization, suggesting vascular bed specific
Bcl-2 function in the endothelium.
PMID- 26444548
TI - Predicting Pathological Features at Radical Prostatectomy in Patients with
Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic
Resonance Imaging.
AB - PURPOSE: The aim of this study was to investigate the prognostic performance of
multiparametric magnetic resonance imaging (mpMRI) and Prostate Imaging Reporting
and Data System (PIRADS) score in predicting pathologic features in a cohort of
patients eligible for active surveillance who underwent radical prostatectomy.
METHODS: A total of 223 patients who fulfilled the criteria for "Prostate Cancer
Research International: Active Surveillance", were included. Mp-1.5 Tesla MRI
examination staging with endorectal coil was performed at least 6-8 weeks after
TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was
assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason
score upgrading, extra capsular extension (ECE), unfavorable prognosis
(occurrence of both upgrading and ECE), large tumor volume (>= 0.5 ml), and
seminal vesicle invasion (SVI). Receiver Operating Characteristic (ROC) curves
and Decision Curve Analyses (DCA) were performed for models with and without
inclusion of PIRADS score. RESULTS: Multivariate analysis demonstrated the
association of PIRADS score with upgrading (P < 0.0001), ECE (P < 0.0001),
unfavorable prognosis (P < 0.0001), and large tumor volume (P = 0.002). ROC
curves and DCA showed that models including PIRADS score resulted in greater net
benefit for almost all the outcomes of interest, with the only exception of SVI.
CONCLUSIONS: mpMRI and PIRADS scoring are feasible tools in clinical setting and
could be used as decision-support systems for a more accurate selection of
patients eligible for AS.
PMID- 26444550
TI - Sensory and instrumental characterization of fast inverting oil-in-water
emulsions for cosmetic application.
AB - OBJECTIVE: The aim of this study was to perform short-term sensory testing and
instrumental (conductivity and rheological) characterization of a fast inverted
oil-in-water (o/w) emulsion base, also known as a SWOP (Switch-Oil-Phase)
emulsion, and reference o/w and water-in-oil (w/o) emulsion bases under various
testing conditions: in the presence of ions and at different temperatures. SWOP
emulsions are known as metastable o/w emulsions, which invert into w/o emulsions
on application of mechanical energy, while rubbing it onto the skin and due to
their properties SWOP emulsion are especially suitable as a cosmetic vehicle in,
for example, sun-protection products. METHODS: Sensory testing, which included
the evaluation of twenty attributes of the investigated emulsion bases, was
performed by a panel of 20 healthy assessors experienced in the evaluation of
cosmetic products. Rheological characterization of the investigated emulsion
bases included continuous flow testing and oscillatory measurements under various
testing conditions. Additionally, conductivity measurements were combined with
rheological characterization to monitor stability changes of investigated
emulsions. The instrumental and sensory results were analysed statistically and
compared. RESULTS: The obtained results indicated that the investigated emulsions
behaved differently in the presence of ions (originating from artificial sweat
solution) and at different temperatures (under storage and application
conditions). Namely, the SWOP emulsion showed similar behaviour to the reference
o/w emulsion under storage conditions, but in the presence of ions and at skin
temperature, the SWOP emulsion was followed by re-establishment of a stable w/o
system, whereas reference o/w emulsion was irreversibly destroyed. The
statistical analysis of chosen sensorial attributes indicated that the reference
w/o emulsion was significantly different in comparison with the reference o/w and
SWOP emulsions, mainly, standing in good agreement with the results of
rheological characterization. CONCLUSION: The study showed that rheological
measurements potentially could be related to certain sensory attributes and used
for faster development of SWOP emulsions in the future. Finally, SWOP emulsions
should be considered for further investigation as suitable vehicles in cosmetic
products due to their favourable physicochemical and sensory characteristics
which could be partially predicted with instrumental characterization.
PMID- 26444549
TI - Immune dysregulation in the functional gastrointestinal disorders.
AB - Gastrointestinal conditions may be broadly classified into two: organic and
functional disease, with functional disorders accounting for the majority of
patients with chronic gastrointestinal symptoms. Functional gastrointestinal
disorders (FGIDs) present with no obvious pathology or well-accepted biochemical
mechanism and, as such, treatment strategies are limited and focus on symptoms
rather than cure. Irritable bowel syndrome and functional dyspepsia are the most
widely recognised FGIDs, and there is a growing body of evidence to suggest an
underlying inflammatory phenotype in subsets with these conditions. Here, we
discuss the current knowledge of immune involvement in FGIDs and the
commonalities between the different manifestations of FGIDs and propose a new
hypothesis, potentially defining an underlying immunopathological basis of these
conditions.
PMID- 26444551
TI - Substituent effects on the optical properties of naphthalenediimides: A frontier
orbital analysis across the periodic table.
AB - A comprehensive theoretical treatment is presented for the electronic excitation
spectra of ca. 50 different mono-, di-, and tetrasubstituted naphthalenediimides
(NDI) using time-dependent density functional theory (TDDFT) at ZORA-CAM
B3LYP/TZ2P//ZORA-BP86/TZ2P with COSMO for simulating the effect of
dichloromethane (DCM) solution. The substituents -XHn are from groups 14-17 and
rows 2-5 of the periodic table. The lowest dipole-allowed singlet excitation (S0
S1 ) of the monosubstituted NDIs can be tuned from 3.39 eV for -F to 2.42 eV for
TeH, while the S0 -S2 transition is less sensitive to substitution with energies
ranging between 3.67 eV for -CH3 and 3.44 eV for -SbH2 . In the case of NDIs with
group-15 and -16 substituents, the optical transitions strongly depend on the
extent to which -XHn is planar or pyramidal as well as on the possible formation
of intramolecular hydrogen bonds. The accumulative effect of double and quadruple
substitution leads in general to increasing bathochromic shifts, but the
increased steric hindrance in tetrasubstituted NDIs can lead to deformations that
diminish the effectiveness of the substituents. Detailed analyses of the Kohn
Sham orbital electronic structure in monosubstituted NDIs reveal the mesomeric
destabilization of the HOMO as the primary cause of the bathochromic shift of the
S0-S1 transition.
PMID- 26444552
TI - A Zebrafish Drug-Repurposing Screen Reveals sGC-Dependent and sGC-Independent Pro
Inflammatory Activities of Nitric Oxide.
AB - Tissue injury and infection trigger innate immune responses. However,
dysregulation may result in chronic inflammation and is commonly treated with
corticosteroids and non-steroidal anti-inflammatory drugs. Unfortunately, long
term administration of both therapeutic classes can cause unwanted side effects.
To identify alternative immune-modulatory compounds we have previously
established a novel screening method using zebrafish larvae. Using this method we
here present results of an in vivo high-content drug-repurposing screen,
identifying 63 potent anti-inflammatory drugs that are in clinical use for other
indications. Our approach reveals a novel pro-inflammatory role of nitric oxide.
Nitric oxide affects leukocyte recruitment upon peripheral sensory nervous system
or epithelial injury in zebrafish larvae both via soluble guanylate cyclase and
in a soluble guanylate cyclase -independent manner through protein S
nitrosylation. Together, we show that our screening method can help to identify
novel immune-modulatory activities and provide new mechanistic insights into the
regulation of inflammatory processes.
PMID- 26444553
TI - On-chip assessment of human primary cardiac fibroblasts proliferative responses
to uniaxial cyclic mechanical strain.
AB - Cardiac cell function is substantially influenced by the nature and intensity of
the mechanical loads the cells experience. Cardiac fibroblasts (CFs) are
primarily involved in myocardial tissue remodeling: at the onset of specific
pathological conditions, CFs activate, proliferate, differentiate, and critically
alter the amount of myocardial extra-cellular matrix with important consequences
for myocardial functioning. While cyclic mechanical strain has been shown to
increase matrix synthesis of CFs in vitro, the role of mechanical cues in CFs
proliferation is unclear. We here developed a multi-chamber cell straining
microdevice for cell cultures under uniform, uniaxial cyclic strain. After
careful characterization of the strain field, we extracted human heart-derived
CFs and performed cyclic strain experiments. We subjected cells to 2% or 8%
cyclic strain for 24 h or 72 h, using immunofluorescence to investigate markers
of cell morphology, cell proliferation (Ki67, EdU, phospho-Histone-H3) and
subcellular localization of the mechanotransduction-associated transcription
factor YAP. Cell morphology was affected by cyclic strain in terms of cell area,
cell and nuclear shape and cellular alignment. We additionally observed a strain
intensity-dependent control of cell growth: a significant proliferation increase
occurred at 2% cyclic strain, while time-dependent effects took place upon 8%
cyclic strain. The YAP-dependent mechano-transduction pathway was similarly
activated in both strain conditions. These results demonstrate a differential
effect of cyclic strain intensity on human CFs proliferation control and provide
insights into the YAP-dependent mechano-sensing machinery of human CFs.
PMID- 26444554
TI - Novel Use of the Nintendo Wii Board for Measuring Isometric Lower Limb Strength:
A Reproducible and Valid Method in Older Adults.
AB - BACKGROUND: Portable, low-cost, objective and reproducible assessment of muscle
strength in the lower limbs is important as it allows clinicians to precisly
track progression of patients undergoing rehabilitation. The Nintendo Wii Balance
Board (WBB) is portable, inexpensive, durable, available worldwide, and may serve
the above function. OBJECTIVE: The purpose of the study was to evaluate (1)
reproducibility and (2) concurrent validity of the WBB for measuring isometric
muscle strength in the lower limb. METHODS: A custom hardware and software was
developed to utilize the WBB for assessment of isometric muscle strength. Thirty
older adults (69.0 +/- 4.2 years of age) were studied on two separate occasions
on both the WBB and a stationary isometric dynamometer (SID). On each occasion,
three recordings were obtained from each device. For the first recording, means
and maximum values were used for further analysis. The test-retest
reproducibility was examined using intraclass correlation coefficients (ICC),
Standard Error of Measurement (SEM), and limits of agreement (LOA). Bland-Altman
plots (BAP) and ICC's were used to explore concurrent validity. RESULTS: No
systematic difference between test-retest was detected for the WBB. ICC within
device were between 0.90 and 0.96 and between-devices were from 0.80 to 0.84. SEM
ranged for the WBB from 9.7 to 13.9%, and for the SID from 11.9 to 13.1%. LOA
ranged for the WBB from 20.3 to 28.7% and for the SID from 24.2 to 26.6%. The BAP
showed no relationship between the difference and the mean. CONCLUSIONS: A high
relative and an acceptable absolute reproducibility combined with a good validity
was found for the novel method using the WBB for measuring isometric lower limb
strength in older adults. Further research using the WBB for assessing lower limb
strength should be conducted in different study-populations.
PMID- 26444555
TI - Bisphosphonate Use and Risk of Implant Revision after Total Hip/Knee
Arthroplasty: A Meta-Analysis of Observational Studies.
AB - OBJECTIVE: Several studies investigated the association between bisphosphonate
use and the risk of implant revision after total hip or knee arthroplasty (THA or
TKA); However, the findings were inconsistent. We performed this meta-analysis to
evaluate the overall relative risk of such an event. METHODS: We searched the
PubMed, EMBASE and Cochrane library databases to identify relevant publications
on April 22, 2015. To calculate the pooled risk ratios (RRs) with 95%
confidential intervals (CIs), a fixed- or random-effects model was applied based
on the heterogeneity across studies. RESULTS: Three cohort studies and one case
control study were included in this meta-analysis. Compared with the
bisphosphonate nonusers, the patients who used bisphosphonates for a long period
of time had a significantly decreased risk of implant revision after THA/TKA
(summary adjusted RR = 0.48, 95% CI: 0.38-0.61), and the summary adjusted RRs for
the users who underwent THA and those who underwent TKA were 0.47 (95% CI: 0.36
0.61) and 0.45 (95% CI: 0.21-0.95), respectively. CONCLUSIONS: Long-term use of
bisphosphonates is correlated with a significantly decreased risk of implant
revision after THA/TKA. However, due to limited number of the included studies,
the findings of the present study should be treated with caution. More well
designed studies are required to further confirm our findings.
PMID- 26444556
TI - Surface-enhanced Raman scattering from AgNP-graphene-AgNP sandwiched
nanostructures.
AB - We developed a facile approach toward hybrid AgNP-graphene-AgNP sandwiched
structures using self-organized monolayered AgNPs from wet chemical synthesis for
the optimized enhancement of the Raman response of monolayer graphene. We
demonstrate that the Raman scattering of graphene can be enhanced 530 fold in the
hybrid structure. The Raman enhancement is sensitively dependent on the hybrid
structure, incident angle, and excitation wavelength. A systematic simulation is
performed, which well explains the enhancement mechanism. Our study indicates
that the enhancement resulted from the plasmonic coupling between the AgNPs on
the opposite sides of graphene. Our approach towards ideal substrates offers
great potential to produce a "hot surface" for enhancing the Raman response of
two-dimensional materials.
PMID- 26444557
TI - Markers for Routine Assessment of Fatigue and Recovery in Male and Female Team
Sport Athletes during High-Intensity Interval Training.
AB - AIM: Our study aimed to investigate changes of different markers for routine
assessment of fatigue and recovery in response to high-intensity interval
training (HIIT). METHODS: 22 well-trained male and female team sport athletes
(age, 23.0 +/- 2.7 years; VO2 max, 57.6 +/- 8.6 mL . min . kg(-1)) participated
in a six-day running-based HIIT-microcycle with a total of eleven HIIT sessions.
Repeated sprint ability (RSA; criterion measure of fatigue and recovery),
countermovement jump (CMJ) height, jump efficiency in a multiple rebound jump
test (MRJ), 20-m sprint performance, muscle contractile properties, serum
concentrations of creatinkinase (CK), c-reactive protein (CRP) and urea as well
as perceived muscle soreness (DOMS) were measured pre and post the training
program as well as after 72 h of recovery. RESULTS: Following the microcycle
significant changes (p < 0.05) in RSA as well as in CMJ and MRJ performance could
be observed, showing a decline (%Delta +/- 90% confidence limits, ES = effect
size; RSA: -3.8 +/- 1.0, ES = -1.51; CMJ: 8.4 +/- 2.9, ES = -1.35; MRJ: 17.4 +/-
4.5, ES = -1.60) and a return to baseline level (RSA: 2.8 +/- 2.6, ES = 0.53;
CMJ: 4.1 +/- 2.9, ES = 0.68; MRJ: 6.5 +/- 4.5, ES = 0.63) after 72 h of recovery.
Athletes also demonstrated significant changes (p < 0.05) in muscle contractile
properties, CK, and DOMS following the training program and after the recovery
period. In contrast, CRP and urea remained unchanged throughout the study.
Further analysis revealed that the accuracy of markers for assessment of fatigue
and recovery in comparison to RSA derived from a contingency table was
insufficient. Multiple regression analysis also showed no correlations between
changes in RSA and any of the markers. CONCLUSIONS: Mean changes in measures of
neuromuscular function, CK and DOMS are related to HIIT induced fatigue and
subsequent recovery. However, low accuracy of a single or combined use of these
markers requires the verification of their applicability on an individual basis.
PMID- 26444559
TI - Substance P and Chronic Pain in Patients with Chronic Inflammation of Connective
Tissue.
AB - OBJECTIVE: Evidence suggests that substance P (SP) is involved in chronic joint
inflammation, such as the pathogenesis of rheumatoid arthritis and
osteoarthritis. The goal of the research was to evaluate the correlation between
chronic pain and changes in the SP level in patients with chronic inflammation of
the connective tissue. METHODS: Patients with osteoarthritis and rheumatoid
arthritis were enrolled in this study. The relationship between chronic pain
intensity and the serum SP concentration was evaluated in these groups of
patients with osteoarthritis and rheumatoid arthritis. RESULTS: The results
showed a positive correlation between the serum SP concentrations and chronic
pain intensity. CONCLUSIONS: 1. The SP serum concentration was significantly
different between the groups of patients with OA and RA. 2. There was a positive
correlation between the serum SP concentration and chronic pain intensity in OA
and RA patients.
PMID- 26444558
TI - Genetic Transformation of Artemisia carvifolia Buch with rol Genes Enhances
Artemisinin Accumulation.
AB - The potent antimalarial drug artemisinin has a high cost, since its only viable
source to date is Artemisia annua (0.01-0.8% DW). There is therefore an urgent
need to design new strategies to increase its production or to find alternative
sources. In the current study, Artemisia carvifolia Buch was selected with the
aim of detecting artemisinin and then enhancing the production of the target
compound and its derivatives. These metabolites were determined by LC-MS in the
shoots of A. carvifolia wild type plants at the following concentrations:
artemisinin (8MUg/g), artesunate (2.24MUg/g), dihydroartemisinin (13.6MUg/g) and
artemether (12.8MUg/g). Genetic transformation of A. carvifolia was carried out
with Agrobacterium tumefaciens GV3101 harboring the rol B and rol C genes.
Artemisinin content increased 3-7-fold in transgenics bearing the rol B gene, and
2.3-6-fold in those with the rol C gene. A similar pattern was observed for
artemisinin analogues. The dynamics of artemisinin content in transgenics and
wild type A.carvifolia was also correlated with the expression of genes involved
in its biosynthesis. Real time qPCR analysis revealed the differential expression
of genes involved in artemisinin biosynthesis, i.e. those encoding amorpha-4, 11
diene synthase (ADS), cytochrome P450 (CYP71AV1), and aldehyde dehydrogenase 1
(ALDH1), with a relatively higher transcript level found in transgenics than in
the wild type plant. Also, the gene related to trichome development and
sesquiterpenoid biosynthesis (TFAR1) showed an altered expression in the
transgenics compared to wild type A.carvifolia, which was in accordance with the
trichome density of the respective plants. The trichome index was significantly
higher in the rol B and rol C gene-expressing transgenics with an increased
production of artemisinin, thereby demonstrating that the rol genes are effective
inducers of plant secondary metabolism.
PMID- 26444560
TI - Biomass and lipid enhancement in Ankistrodesmus sp. cultured with reused and
minimal nutrients media.
AB - Microalgae are a promising feedstock for biofuel production. Lipid content in
microalgae could be enhanced under nutrient depletion. This work investigated the
effect of the nutrient on lipid accumulation in Ankistrodesmus sp. culture. Batch
cultures were carried out using fresh BG11 medium, and after the harvest, the
medium was reused for the next culture; this method was repeated two times. The
maximum lipid productivity of 29.75 mg L(-1) day(-1) was obtained from the
culture with the second reuse medium. In continuous cultures, Ankistrodesmus sp.
was cultured in both fresh and modified BG11 mediums. The modified BG11 medium
was adjusted to resemble the content of the first reuse medium. As a comparison
between batch and continuous cultures, it was proven that the productivity in the
continuous culture was better than in the batch, where the achievable maximum
biomass and lipid were 188.30 and 38.32 mg L(-1) day(-1). The maximum lipid
content of 34.22% was obtained from the continuous culture at a dilution rate of
0.08 day(-1), whereas the maximum saturated and unsaturated fatty acid
productivities of 79.96 and 104.54 mg L(-1) day(-1) were obtained at a dilution
rate of 0.16 day(-1.)
PMID- 26444561
TI - Cells on biomaterials--some aspects of elemental analysis by means of electron
probes.
AB - Electron probe X-ray microanalysis enables concomitant observation of specimens
and analysis of their elemental composition. The method is attractive for
engineers developing tissue-compatible biomaterials. Either changes in element
composition of cells or biomaterial can be defined according to well-established
preparation and quantification procedures. However, the qualitative and
quantitative elemental analysis appears more complicated when cells or thin
tissue sections are deposited on biomaterials. X-ray spectra generated at the
cell/tissue-biomaterial interface are modelled using a Monte Carlo simulation of
a cell deposited on borosilicate glass. Enhanced electron backscattering from
borosilicate glass was noted until the thickness of the biological layer
deposited on the substrate reached 1.25 MUm. It resulted in significant increase
in X-ray intensities typical for the elements present in the cellular part. In
this case, the mean atomic number value of the biomaterial determines the
strength of this effect. When elements are present in the cells only, the
positive linear relationship appears between X-ray intensities and cell
thickness. Then, spatial dimensions of X-ray emission for the particular elements
are exclusively in the range of the biological part and the intensities of X-rays
become constant. When the elements are present in both the cell and the
biomaterial, X-ray intensities are registered for the biological part and the
substrate simultaneously leading to a negative linear relationship of X-ray
intensities in the function of cell thickness. In the case of the analysis of an
element typical for the biomaterial, strong decrease in X-ray emission is
observed in the function of cell thickness as the effect of X-ray absorption and
the limited excitation range to biological part rather than to the substrate.
Correction procedures for calculations of element concentrations in thin films
and coatings deposited on substrates are well established in materials science,
but little is known about factors that have to be taken into account to
accurately quantify bioelements in thin and semi-thick biological samples. Thus
thorough tests of currently available quantification procedures are required to
verify their applicability to cells or tissues deposited on the biomaterials.
PMID- 26444562
TI - High-Performance Lead-Free Piezoceramics with High Curie Temperatures.
AB - A bismuth ferrite and barium titanate solid solution compound can achieve good
piezoelectric properties with a high Curie temperature when fabricated with low
temperature sintering followed by a water-quenching process, with no complicated
grain alignment processes performed. By adding the super-tetragonal bismuth
gallium oxide to the compound, the piezoelectric properties are as good as those
of lead zirconate titanate ceramics.
PMID- 26444563
TI - Relationship between Objective and Subjective Atmospheric Visibility and Its
Influence on Willingness to Accept or Pay in China.
AB - This study is to distinguish the objective and subjective measures of atmospheric
visibility, and investigate the relationship between the two measures as well as
the effect on the people's behavioral intentions on air pollution in China. A
mixed method was adopted in this study combining both lab experiments to measure
objective atmospheric visibility and a questionnaire survey to measure subjective
atmospheric visibility. The regression results show that: (a) The people's
perception of atmospheric visibility is based on objective information about the
ambient air (Relative Humidity, PM2.5, Atmospheric Visibility) and there are some
turning points that could enable people to distinguish good and poor air quality;
(b) The people's perception of visibility has a significant effect on either
their willingness-to-accept (WTA) the visibility or on their willingness-to-pay
(WTP) for improving the air quality;
PMID- 26444564
TI - Factors Affecting Growth of Tengmalm's Owl (Aegolius funereus) Nestlings: Prey
Abundance, Sex and Hatching Order.
AB - In altricial birds, energy supply during growth is a major predictor of the
physical condition and survival prospects of fledglings. A number of experimental
studies have shown that nestling body mass and wing length can vary with
particular extrinsic factors, but between-year observational data on this topic
are scarce. Based on a seven-year observational study in a central European
Tengmalm's owl population we examine the effect of year, brood size, hatching
order, and sex on nestling body mass and wing length, as well as the effect of
prey abundance on parameters of growth curve. We found that nestling body mass
varied among years, and parameters of growth curve, i.e. growth rate and
inflection point in particular, increased with increasing abundance of the owl's
main prey (Apodemus mice, Microtus voles), and pooled prey abundance (Apodemus
mice, Microtus voles, and Sorex shrews). Furthermore, nestling body mass varied
with hatching order and between sexes being larger for females and for the first
hatched brood mates. Brood size had no effect on nestling body mass.
Simultaneously, we found no effect of year, brood size, hatching order, or sex on
the wing length of nestlings. Our findings suggest that in this temperate owl
population, nestling body mass is more sensitive to prey abundance than is wing
length. The latter is probably more limited by the physiology of the species.
PMID- 26444565
TI - Development of Active Films From Pectin and Fruit Extracts: Light Protection,
Antioxidant Capacity, and Compounds Stability.
AB - Pectin films containing fruit extracts were developed and tested in relation to
ultraviolet light transmission, phytochemical contents, and antioxidant capacity
during 90 d shelf life storage. Aqueous and alcoholic extracts from 5 different
fruits (acerola, cashew apple, papaya, pequi, and strawberry) were obtained.
Because the alcoholic extracts from acerola, cashew apple, and strawberry
presented the highest phytochemical content and antioxidant capacity, they were
incorporated into pectin films individually or as a mixture. Incorporation of
these extracts into pectin films provided antioxidant capacity while retaining
the physical properties. The pectin films containing fruit extract acted as
adequate light barrier and prevented photooxidation. Among the prepared films,
the pectin film containing acerola extract afforded the highest antioxidant
capacity, with a half-life of 99 d. Overall, the results revealed that
incorporation of fruit extracts into pectin films potentially produces
antioxidant films and coatings for different food applications. PRACTICAL
APPLICATION: The production of pectin films incorporated with fruit extract is
based on combination of the antioxidant activity, natural color, and optical
barrier properties from fruit phytochemical components to the active film. This
film could be potentially used as active packing on food products in order to
protect their nutrients against free radicals action and photooxidation and,
hence, preserve the quality, integrity, and safety of food during the storage
period.
PMID- 26444567
TI - The Changing Landscape of Noninvasive Ventilation in the Intensive Care Unit.
PMID- 26444566
TI - Genetic Polymorphisms in Inflammasome-Dependent Innate Immunity among Pediatric
Patients with Severe Renal Parenchymal Infections.
AB - BACKGROUND: Inflammasome innate immune response activation has been demonstrated
in various inflammatory diseases and microbial infections. However, to our
knowledge, no study has examined the inflammasome-dependent pathways in patients
with urinary tract infection. Defective or variant genes associated with innate
immunity are believed to alter the host's susceptibility to microbial infection.
This study investigated genetic polymorphisms in genes encoding inflammasomes and
the subsequent released cytokines in pediatric patients with severe renal
parenchymal infections. METHODOLOGY: This study included patients diagnosed with
acute pyelonephritis (APN) and acute lobar nephronia (ALN) who had no underlying
disease or structural anomalies other than vesicoureteral reflux (VUR). Single
nucleotide polymorphism (SNP) genotyping was performed in the genes associated
with inflammasome formation and activation (NLRP3, CARD8) and subsequent IL-1beta
cytokine generation (IL-1beta). PRINCIPAL FINDINGS: A total of 40 SNPs were
selected for initial genotyping. Analysis of samples from 48 patients each and 96
controls revealed that only nine SNPs (five SNPs in NLRP3; three SNPs in CARD8;
one SNP in IL-1beta) had heterozygosity rates >0.01. Hardy-Weinberg equilibrium
was satisfied for the observed genotype frequencies of these SNPs. Analysis
excluding patients with VUR, a well-known risk factor for severe UTIs, revealed a
lower frequency of the CC genotype in NLRP3 (rs4612666) in patients with APN and
ALN than in controls. Correction for multiple-SNP testing showed that the non-VUR
subgroup of the APN+ALN combined patient groups remained significantly different
from the control group (P < 0.0055). CONCLUSIONS: This study is the first to
suggest that the inflammasome-dependent innate immunity pathway is associated
with the pathogenesis of pediatric severe renal parenchymal infections. Further
investigation is warranted to clarify its pathogenic mechanism.
PMID- 26444568
TI - Is C50 a superaromat? Evidence from electronic structure and ring current
calculations.
AB - The fullerene-50 is a 'magic number' cage according to the 2(N + 1)(2) rule. For
the three lowest isomers of C50 with trigonal and pentagonal symmetries, we
calculate the sphericity index, the spherical parentage of the occupied pi
orbitals, and the current density in an applied magnetic field. The minimal
energy isomer, with D3 symmetry, comes closest to a spherical aromat or a
superaromat. In the D5h bond-stretch isomers the electronic structure shows
larger deviations from the ideal spherical shells, with hybridisation or even
reversal of spherical parentages. It is shown that relative stabilities of
fullerene cages do not correlate well with aromaticity, unlike the magnetic
properties which are very sensitive indicators of spherical aromaticity.
Superaromatic diamagnetism in the D3 cage is characterized by global diatropic
currents, which encircle the whole cage. The breakdown of sphericity in the D5h
cages gives rise to local paratropic countercurrents.
PMID- 26444569
TI - Blood Transfusion and 30-Day Mortality in Patients With Coronary Artery Disease
and Anemia Following Noncardiac Surgery.
AB - IMPORTANCE: Although liberal blood transfusion thresholds have not been
beneficial following noncardiac surgery, it is unclear whether higher thresholds
are appropriate for patients who develop postoperative myocardial infarction
(MI). OBJECTIVE: To evaluate the association between postoperative blood
transfusion and mortality in patients with coronary artery disease and
postoperative MI following noncardiac surgery. DESIGN, SETTING, AND PARTICIPANTS:
Retrospective cohort study involving Veterans Affairs facilities from January 1,
2000, to December 31, 2012. A total of 7361 patients with coronary artery disease
who underwent inpatient noncardiac surgery and had a nadir postoperative
hematocrit between 20% and 30%. Patients with significant bleeding, including any
preoperative blood transfusion or transfusion of greater than 4 units during the
intraoperative or postoperative setting, were excluded. Mortality rates were
compared using both logistic regression and propensity score matching. Patients
were stratified by postoperative nadir hematocrit and the presence of
postoperative MI. EXPOSURE: Initial postoperative blood transfusion. MAIN
OUTCOMES AND MEASURES: The 30-day postoperative mortality rate. RESULTS: Of the
7361 patients, 2027 patients (27.5%) received at least 1 postoperative blood
transfusion. Postoperative mortality occurred in 267 (3.6%), and MI occurred in
271 (3.7%). Among the 5334 patients without postoperative blood transfusion,
lower nadir hematocrit was associated with an increased risk for mortality
(hematocrit of 20% to <24%: 7.3%; 24% to <27%: 3.7%; and 27% to 30%: 1.6%; P <
.01). In patients with postoperative MI, blood transfusion was associated with
lower mortality, for those with hematocrit of 20% to 24% (odds ratio, 0.28; 95%
CI, 0.13-0.64). In patients without postoperative MI, transfusion was associated
with significantly higher mortality for those with hematocrit of 27% to 30% (odds
ratio, 3.21; 95% CI, 1.85-5.60). CONCLUSIONS AND RELEVANCE: These findings
support a restrictive postoperative transfusion strategy in patients with stable
coronary artery disease following noncardiac surgery. However, interventional
studies are needed to evaluate the use of a more liberal transfusion strategy in
patients who develop postoperative MI.
PMID- 26444570
TI - Bullying and Its Prevention Among Intensive Care Nurses.
AB - PURPOSE: International studies report that nurse bullying is a common occurrence.
The intensive care unit (ICU) is known for its high stress levels, one factor
thought to increase bullying. No studies were found that investigated bullying in
this population. The purpose of this study was to describe the prevalence of ICU
nurse bullying and what measures were taken to prevent bullying. DESIGN: This was
a descriptive study of a convenience sample of 156 ICU nurses from five medical
centers in Israel. Data collection was conducted over a 10-month period in 2012
and 2013. METHODS: After ethical approval, three questionnaires (background
characteristics, Negative Acts Questionnaire-Revised, and Prevention of Bullying
Questionnaire) were administered according to unit preference. Descriptive
statistics were calculated for all responses and a Pearson product moment
correlation was calculated to determine the relationship between bullying and its
prevention. FINDINGS: Most of the nurses in the study were married, female staff
nurses with a baccalaureate in nursing. No participant responded that they had
been bullied daily, but 29% reported that they were a victim of bullying. The
mean bullying score was 1.6 +/- 1.4 out of 5. The mean prevention score was 2.4
+/- 0.3 out of 4. Significant differences were found between hospitals on
bullying, F (4,155) = 2.7, p = .039, and between hospitals, F (4,155) = 2.9, p =
.026, and units, F (5,143) = 3.4, p = .006, on prevention. The Prevention Scale
significantly correlated with the bullying scale (r = .58, p < .001). No other
variables were found to be associated with either bullying or prevention scores.
CONCLUSIONS: An alarming percentage of nurses were victims of bullying. Levels of
bullying were low to moderate. Level of prevention was weak or moderate. The
higher the level of bullying, the lower the level of prevention. The work
environment as opposed to individual characteristics seems to have an impact on
bullying and its prevention. CLINICAL RELEVANCE: More measures must be taken to
prevent bullying. Nurses must be educated to accept only a zero tolerance to
bullying and to report bullying when confronted by bullying.
PMID- 26444571
TI - Local outbreak of hepatitis E: a rare cause of viral hepatitis in Australia.
AB - Hepatitis E is a not uncommon cause of viral hepatitis globally but is relatively
rare in Australia. Here, we report a case of acute hepatitis E that was acquired
in Sydney and was part of a cluster believed to be infected locally. This is to
our knowledge the first known outbreak of locally acquired hepatitis E in
Australia. We discuss pathogenesis, clinical features and means by which further
spread of infection can be limited.
PMID- 26444572
TI - Reward related neurotransmitter changes in a model of depression: An in vivo
microdialysis study.
AB - OBJECTIVES: The self-medication hypothesis assumes that symptoms related to
potential monoaminergic deficits in depression may be relieved by drug abuse. The
aim of this study was to elucidate the neurotransmitter changes in a rat model of
depression by measuring their levels in the nucleus accumbens shell, which is
typically involved in the drug of abuse acquisition mechanism. METHODS:
Depression was modelled by the olfactory bulbectomy (OBX) in Wistar male rats. In
vivo microdialysis was performed, starting from the baseline and following after
a single methamphetamine injection and behaviour was monitored. The determination
of neurotransmitters and their metabolites was performed by high-performance
liquid chromatography combined with mass spectrometry. RESULTS: OBX animals had
lower basal levels of dopamine and serotonin and their metabolites. However,
gamma-aminobutyric acid (GABA) and glutamate levels were increased. The
methamphetamine injection induced stronger dopamine and serotonin release in the
OBX rats and lower release of glutamate in comparison with sham-operated rats;
GABA levels did not differ significantly. CONCLUSIONS: This study provides an
evidence of mesolimbic neurotransmitter changes in the rat model of depression
which may elucidate mechanisms underlying intravenous self-administration studies
in which OBX rats were demonstrated to have higher drug intake in comparison to
intact controls.
PMID- 26444573
TI - Transcriptome Analysis of CD4+ T Cells in Coeliac Disease Reveals Imprint of
BACH2 and IFNgamma Regulation.
AB - Genetic studies have to date identified 43 genome wide significant coeliac
disease susceptibility (CD) loci comprising over 70 candidate genes. However, how
altered regulation of such disease associated genes contributes to CD
pathogenesis remains to be elucidated. Recently there has been considerable
emphasis on characterising cell type specific and stimulus dependent genetic
variants. Therefore in this study we used RNA sequencing to profile over 70
transcriptomes of CD4+ T cells, a cell type crucial for CD pathogenesis, in both
stimulated and resting samples from individuals with CD and unaffected controls.
We identified extensive transcriptional changes across all conditions, with the
previously established CD gene IFNy the most strongly up-regulated gene (log2
fold change 4.6; P(adjusted) = 2.40x10(-11)) in CD4+ T cells from CD patients
compared to controls. We show a significant correlation of differentially
expressed genes with genetic studies of the disease to date (P(adjusted) =
0.002), and 21 CD candidate susceptibility genes are differentially expressed
under one or more of the conditions used in this study. Pathway analysis revealed
significant enrichment of immune related processes. Co-expression network
analysis identified several modules of coordinately expressed CD genes. Two
modules were particularly highly enriched for differentially expressed genes
(P<2.2x10(-16)) and highlighted IFNy and the genetically associated transcription
factor BACH2 which showed significantly reduced expression in coeliac samples
(log2FC -1.75; P(adjusted) = 3.6x10(-3)) as key regulatory genes in CD. Genes
regulated by BACH2 were very significantly over-represented among our
differentially expressed genes (P<2.2x10(-16)) indicating that reduced expression
of this master regulator of T cell differentiation promotes a pro-inflammatory
response and strongly corroborates genetic evidence that BACH2 plays an important
role in CD pathogenesis.
PMID- 26444575
TI - FTIR microscopy reveals distinct biomolecular profile of crustacean digestive
glands upon subtoxic exposure to ZnO nanoparticles.
AB - Biomolecular profiling with Fourier-Transform InfraRed Microscopy was performed
to distinguish the Zn(2+)-mediated effects on the crustacean (Porcellio scaber)
digestive glands from the ones elicited by the ZnO nanoparticles (NPs). The
exposure to ZnO NPs or ZnCl2 (1500 and 4000 ug Zn/g of dry food) activated
different types of metabolic pathways: some were found in the case of both
substances, some only in the case of ZnCl2, and some only upon exposure to ZnO
NPs. Both the ZnO NPs and the ZnCl2 increased the protein (~1312 cm(-1); 1720
1485 cm(-1)/3000-2830 cm(-1)) and RNA concentration (~1115 cm(-1)). At the
highest exposure concentration of ZnCl2, where the effects occurred also at the
organismal level, some additional changes were found that were not detected upon
the ZnO NP exposure. These included changed carbohydrate (most likely glycogen)
concentrations (~1043 cm(-1)) and the desaturation of cell membrane lipids (~3014
cm(-1)). The activation of novel metabolic pathways, as evidenced by changed
proteins' structure (at 1274 cm(-1)), was found only in the case of ZnO NPs. This
proves that Zn(2+) are not the only inducers of the response to ZnO NPs. Low
bioavailable fraction of Zn(2+) in the digestive glands exposed to ZnO NPs
further supports the role of particles in the ZnO NP-generated effects. This
study provides the evidence that ZnO NPs induce their own metabolic responses in
the subtoxic range.
PMID- 26444576
TI - Response to Carlsson et al.: Prevalence and incidence of diabetes mellitus: a
nationwide population-based pharmaco-epidemiological study in Sweden.
PMID- 26444577
TI - Asthma-like symptoms, diagnostic tests, and asthma medication use in children and
adolescents: a population-based nationwide survey.
AB - OBJECTIVE: This study aimed to estimate the prevalence of asthma-like symptoms,
current asthma (CA), asthma diagnostic tests, and inhaled medication use in a
nationwide pediatric population (<18 years). METHODS: Pediatric-specific data
from a cross-sectional, population-based telephone survey (INAsma study) in
Portugal were analyzed. CA was defined as lifetime asthma and (1) wheezing, (2)
waking with breathlessness, or (3) asthma attack in the previous 12 months,
and/or (4) taking asthma medication at the time of the interview. RESULTS: In
total, 716 children were included. The prevalence of asthma-like symptoms was
39.4% [95% confidence interval (95% CI): 35.7-43.3]. The most common symptoms
were waking with cough (30.9%) and wheezing (19.1%). The prevalence of CA was
8.4% (95% CI: 6.6-10.7). Among children with CA, 79.9% and 52.9% reported prior
allergy testing and pulmonary function testing (PFT), respectively. Inhaled
medication use in the previous 12 months was reported by 67.6% (reliever
inhalers, 40.1%; controller inhalers, 41.5%). Those who only used inhaled
reliever medications experienced more asthma attacks [odds ratio (OR): 2.69].
Significantly fewer children with CA living in rural areas than those living in
urban areas had undergone PFT or used inhaled medication (OR: 0.06 for PFT, 0.20
for medication]. CONCLUSIONS: The prevalence of CA in the Portuguese pediatric
population was 8.4%. Only half of children with CA had ever undergone PFT; more
than half did not use controller inhalers, and those who only used reliever
inhalers reported more asthma attacks. These findings suggest that asthma
management has been substandard, mainly in rural areas.
PMID- 26444578
TI - Purification of intact chloroplasts from marine plant Posidonia oceanica suitable
for organelle proteomics.
AB - Posidonia oceanica is a marine angiosperm, or seagrass, adapted to grow to the
underwater life from shallow waters to 50 m depth. This raises questions of how
their photosynthesis adapted to the attenuation of light through the water column
and leads to the assumption that biochemistry and metabolism of the chloroplast
are the basis of adaptive capacity. In the present study, we described a protocol
that was adapted from those optimized for terrestrial plants, to extract
chloroplasts from as minimal tissue as possible. We obtained the best balance
between tissue amount/intact chloroplasts yield using one leaf from one plant.
After isopynic separations, the chloroplasts purity and integrity were evaluated
by biochemical assay and using a proteomic approach. Chloroplast proteins were
extracted from highly purified organelles and resolved by 1DE SDS-PAGE. Proteins
were sequenced by nLC-ESI-IT-MS/MS of 1DE gel bands and identified against NCBInr
green plant databases, Dr. Zompo database for seagrasses in a local customized
dataset. The curated localization of proteins in sub-plastidial compartments
(i.e. envelope, stroma and thylakoids) was retrieved in the AT_CHLORO database.
This purification protocol and the validation of compartment markers may serve as
basis for sub-cellular proteomics in P. oceanica and other seagrasses.
PMID- 26444579
TI - Resolving power for the diffusion orientation distribution function.
AB - PURPOSE: The diffusion orientation distribution function (dODF) is primarily used
for white matter fiber tractography. Here the resolving power of the dODF is
investigated for a simple diffusion model of two intersecting axonal fiber
bundles. METHODS: The resolving power for the dODF is evaluated using the Sparrow
criterion. This is determined for the exact dODF and also for q-space imaging
(QSI), q-ball, and kurtosis approximations. RESULTS: Based on theoretical and
numerical calculations, the resolving power is found to depend on the eigenvalues
of the diffusion model and on the degree of radial weighting for the dODF. The
resolving powers of the QSI and q-ball dODFs improve with increased b-value. The
kurtosis dODF has a resolving power similar to that of the exact dODF.
CONCLUSION: The dODFs, whether exact or approximate, have finite resolving powers
that limit their sensitivity to fiber crossings. The resolving powers for the
different dODFs considered here provide convenient benchmarks for assessing and
comparing their performance. Magn Reson Med 76:679-688, 2016. (c) 2015 Wiley
Periodicals, Inc.
PMID- 26444580
TI - Association of Skin Cancer and Indoor Tanning in Sexual Minority Men and Women.
AB - Importance: Skin cancer, the most common cancer in the United States, is highly
associated with outdoor and indoor tanning behaviors. Although indoor tanning has
been suggested to be more common among sexual minority (self-reported as
homosexual, gay, or bisexual) men compared with heterosexual men, whether rates
of skin cancer vary by sexual orientation is unknown. Objective: To investigate
whether skin cancer prevalence and indoor tanning behaviors vary by sexual
orientation in the general population. Design, Setting, and Participants: We
performed a cross-sectional study using data from the 2001, 2003, 2005, and 2009
California Health Interview Surveys (CHISs) and the 2013 National Health
Interview Survey (NHIS) of population-based samples of the California and US
noninstitutionalized civilian population. Participants included 192 575 men and
women 18 years or older who identified as heterosexual or a sexual minority. Main
Outcomes and Measures: Self-reported lifetime history of skin cancer and 12-month
history of indoor tanning. Results: The study included 78 487 heterosexual men,
3083 sexual minority men, 107 976 heterosexual women, and 3029 sexual minority
women. Sexual minority men were more likely than heterosexual men to report
having skin cancer (2001-2005 CHISs: adjusted odds ratio [aOR], 1.56; 95% CI,
1.18-2.06, P < .001; 2013 NHIS: aOR, 2.13; 95% CI, 1.14-3.96, P = .02) and having
tanned indoors (2009 CHIS: aOR, 5.80; 95% CI, 2.90-11.60, P < .001; 2013 NHIS:
aOR, 3.16; 95% CI, 1.77-5.64, P < .001). Sexual minority women were less likely
than heterosexual women to report having had nonmelanoma skin cancer (2001-2005
CHIS: aOR, 0.56; 95% CI, 0.37-0.86, P = .008) and having tanned indoors (2009
CHIS: aOR, 0.43; 95% CI, 0.20-0.92, P = .03; 2013 NHIS: aOR, 0.46; 95% CI, 0.26
0.81, P = .007). Conclusions and Relevance: Sexual minority men indoor tan more
frequently and report higher rates of skin cancer than heterosexual men. Primary
and secondary prevention efforts targeted at sexual minority men might reduce
risk factors for, and consequences of, skin cancer.
PMID- 26444581
TI - Ischemic placental syndrome--prediction and new disease monitoring.
AB - The last decade has seen an improved understanding of the cause of the
development of pathologies such as gestational hypertension, preeclampsia,
intrauterine growth restriction, intrauterine fetal death or placental abruption.
Nowadays, we know that most conditions within this group share the same
pathogenesis, the cause of which is placental ischemia. The following review is
an attempt to propose a new method for prediction, diagnosis and--above all-
appropriate monitoring of pregnant women and fetuses developing the ischemic
placental syndrome with the use of tests that are new but yet widely available in
clinical diagnosis. They are closely related to the condition's pathogenesis,
therefore their elevated levels may predate clinical symptoms, and--most
importantly--they correlate with syndrome aggravation and the occurrence of
complications. Perhaps, the new look will allow us to improve perinatal results
by reducing mortality and severe complications in pregnant women and fetal deaths
resulting from sudden intrauterine fetal death or placental abruption.
PMID- 26444582
TI - Serious Neurologic Events after Epidural Glucocorticoid Injection--The FDA's Risk
Assessment.
PMID- 26444583
TI - Genotyping of Mycobacterium leprae strains from a region of high endemic leprosy
prevalence in India.
AB - Leprosy is still a major health problem in India which has the highest number of
cases. Multiple locus variable number of tandem repeat analysis (MLVA) and single
nucleotide polymorphism (SNP) have been proposed as tools of strain typing for
tracking the transmission of leprosy. However, empirical data for a defined
population from scale and duration were lacking for studying the transmission
chain of leprosy. Seventy slit skin scrapings were collected from Purulia (West
Bengal), Miraj (Maharashtra), Shahdara (Delhi), and Naini (UP) hospitals of The
Leprosy Mission (TLM). SNP subtyping and MLVA on 10 VNTR loci were applied for
the strain typing of Mycobacterium leprae. Along with the strain typing
conventional epidemiological investigation was also performed to trace the
transmission chain. In addition, phylogenetic analysis was done on variable
number of tandem repeat (VNTR) data sets using sequence type analysis and
recombinational tests (START) software. START software performs analyses to aid
in the investigation of bacterial population structure using multilocus sequence
data. These analyses include data summary, lineage assignment, and tests for
recombination and selection. Diversity was observed in the cross-sectional survey
of isolates obtained from 70 patients. Similarity in fingerprinting profiles
observed in specimens of cases from the same family or neighborhood locations
indicated a possible common source of infection. The data suggest that these
VNTRs including subtyping of SNPs can be used to study the sources and
transmission chain in leprosy, which could be very important in monitoring of the
disease dynamics in high endemic foci. The present study strongly indicates that
multi-case families might constitute epidemic foci and the main source of M.
leprae in villages, causing the predominant strain or cluster infection leading
to the spread of leprosy in the community.
PMID- 26444584
TI - Phylogenetic analysis of a circulating hepatitis C virus recombinant strain 1b/1a
isolated in a French hospital centre.
AB - Genetic recombination is now a well-established feature of the hepatitis C virus
(HCV) variability and evolution, with the recent identification of circulating
recombinant forms. In Amiens University Hospital Centre (France), a discrepancy
of genotyping results was observed for 9 samples, between their 5' untranslated
region assigned to genotype 1b and their NS5B region assigned to genotype 1a,
suggesting the existence of a recombinant strain. In the present study, clinical
and phylogenetic analyses of these isolates were conducted and a putative
relationship with previously identified HCV 1b/1a recombinants was investigated.
The results revealed that all 9 strains displayed a breakpoint within the
beginning of the core protein, were closely related between each other and with
the H23 strain identified in Uruguay (Moreno et al., 2009). Then, the clinical
characteristics of the 9 unlinked individuals infected with this 1b/1a genotype
were analysed. This is the first report on the circulation, in a French
population, of a HCV recombinant strain 1b/1a. The identification of this
genotype in other patients and in other geographical zones would allow to further
investigate its prevalence in the population and to better understand its
molecular epidemiology.
PMID- 26444585
TI - The role of Neuropeptide Y in fear conditioning and extinction.
AB - While anxiety disorders are the brain disorders with the highest prevalence and
constitute a major burden for society, a considerable number of affected people
are still treated insufficiently. Thus, in an attempt to identify potential new
anxiolytic drug targets, neuropeptides have gained considerable attention in
recent years. Compared to classical neurotransmitters they often have a
regionally restricted distribution and may bind to several distinct receptor
subtypes. Neuropeptide Y (NPY) is a highly conserved neuropeptide that is
specifically concentrated in limbic brain areas and signals via at least 5
different G-protein-coupled receptors. It is involved in a variety of
physiological processes including the modulation of emotional-affective
behaviors. An anxiolytic and stress-reducing property of NPY is supported by many
preclinical studies. Whether NPY may also interact with processing of learned
fear and fear extinction is comparatively unknown. However, this has considerable
relevance since pathological, inappropriate and generalized fear expression and
impaired fear extinction are hallmarks of human post-traumatic stress disorder
and a major reason for its treatment-resistance. Recent evidence from different
laboratories emphasizes a fear-reducing role of NPY, predominantly mediated by
exogenous NPY acting on Y1 receptors. Since a reduction of fear expression was
also observed in Y1 receptor knockout mice, other Y receptors may be equally
important. By acting on Y2 receptors, NPY promotes fear extinction and generates
a long-term suppression of fear, two important preconditions that could support
cognitive behavioral therapies in human patients. A similar effect has been
demonstrated for the closely related pancreatic polypeptide (PP) when acting on
Y4 receptors. Preliminary evidence suggests that NPY modulates fear in particular
by activation of Y1 and Y2 receptors in the basolateral and central amygdala,
respectively. In the basolateral amygdala, NPY signaling activates inhibitory G
protein-coupled inwardly-rectifying potassium channels or suppresses
hyperpolarization-induced I(h) currents in a Y1 receptor-dependent fashion,
favoring a general suppression of neuronal activity. A more complex situation has
been described for the central extended amygdala, where NPY reduces the frequency
of inhibitory and excitatory postsynaptic currents. In particular the inhibition
of long-range central amygdala output neurons may result in a Y2 receptor
dependent suppression of fear. The role of NPY in processes of learned fear and
fear extinction is, however, only beginning to emerge, and multiple questions
regarding the relevance of endogenous NPY and different receptor subtypes remain
elusive. Y2 receptors may be of particular interest for future studies, since
they are the most prominent Y receptor subtype in the human brain and thus among
the most promising therapeutic drug targets when translating preclinical evidence
to potential new therapies for human anxiety disorders.
PMID- 26444586
TI - Y2 receptor signalling in NPY neurons controls bone formation and fasting induced
feeding but not spontaneous feeding.
AB - Y2 receptors have been implicated in the development of obesity and are a
potential target for obesity treatment due to their known role of inhibiting
neuropeptide Y (NPY) induced feeding responses. However, the precise neuronal
population on which Y2 receptors act to fulfil this role is less clear. Here we
utilise a novel inducible, postnatal onset NPY neurons specific deletion model to
investigate the functional consequences of loss of Y2 signalling in this
population of neurons on feeding and energy homeostasis regulation. While the
consequences of lack of Y2 signalling in NPY neurons are confirmed in terms of
the uncoupling of suppression/increasing of NPY and pro-opiomelanocortin (POMC)
mRNA expression in the arcuate nuclei (Arc), respectively, this lack of Y2
signalling surprisingly does not have any significant effect on spontaneous food
intake. Fasting induced food intake, however, is strongly increased but only in
the first 1h after re-feeding. Consequently no significant changes in body weight
are being observed although body weight gain is increased in male mice after
postnatal onset Y2 deletion. Importantly, another known function of central Y2
receptor signalling, the suppression of bone formation is conserved in this
conditional model with whole body bone mineral content being decreased. Taken
together this model confirms the critical role of Y2 signalling to control NPY
and associated POMC expression in the Arc, but also highlights the possibility
that others, non-NPY neuronal Y2 receptors, are also involved in controlling
feeding and energy homeostasis regulation.
PMID- 26444587
TI - Decreased maternal hypothalamic-pituitary-adrenal axis activity in very severely
obese pregnancy: Associations with birthweight and gestation at delivery.
AB - BACKGROUND: The maternal hypothalamic-pituitary-adrenal-axis (HPAA) undergoes
dramatic activation during pregnancy. Increased cortisol and corticotrophin
releasing-hormone (CRH) associate with low birthweight and preterm labor. In non
pregnant obesity, the HPAA is activated but circulating cortisol levels are
normal or lower than in lean women. We hypothesized that maternal cortisol levels
would be lower in obese pregnancy, and would associate with increased fetal size
and length of gestation. METHOD: Fasting serum cortisol was measured at 16, 28
and 36 weeks gestation and at 3-6 months postpartum in 276 severely obese and 135
lean women. In a subset of obese (n=20) and lean (n=20) we measured CRH, hormones
that regulate bioavailable cortisol (corticosteroid-binding-globulin, estradiol,
estriol, and progesterone). Urinary glucocorticoid metabolites were measured in
pregnant (obese n=6, lean n=5) and non-pregnant (obese n=7, lean n=7) subjects.
RESULTS: Maternal cortisol and HPAA hormones were lower in obese pregnancy. Total
urinary glucocorticoid metabolites increased significantly in lean pregnancy, but
not in obese. Lower maternal cortisol in obese tended to be associated with
increased birthweight (r=-0.13, p=0.066). In obese, CRH at 28 weeks correlated
inversely with gestational length (r=-0.49, p=0.04), and independently predicted
gestational length after adjustment for confounding factors (mean decrease in CRH
of -0.25 pmol/L (95% CI -0.45 to -0.043 pmol/L) per/day increase in gestation).
CONCLUSION: In obese pregnancy, lower maternal cortisol without an increase in
urinary glucocorticoid clearance may indicate a lesser activation of the HPAA
than in lean pregnancy. This may offer a novel mechanism underlying increased
birthweight and longer gestation in obese pregnancy.
PMID- 26444588
TI - Are leptin levels increased among people with schizophrenia versus controls? A
systematic review and comparative meta-analysis.
AB - OBJECTIVE: Leptin may play a role in the pathophysiology of schizophrenia and it
remains unclear if levels are raised compared to controls. Therefore, we
performed a systematic review and meta-analysis comparing leptin levels among
people with schizophrenia and controls. METHOD: Two authors independently
searched major electronic databases from inception until June 2015 for studies
measuring blood leptin levels among people with schizophrenia and controls.
Random effects meta-analysis calculating hedges g and 95% confidence intervals
(CI) and meta-regression analyses were conducted. RESULTS: Twenty-seven articles
representing 1674 individuals with schizophrenia (34.6 +/- 6.8 years, 55% male (0
100%), BMI 25.2 +/- 3.1) and 2033 controls (33.9 +/- 7.0 years, 51% male (0
100%), BMI=24.1 +/- 2.1) were included. Across all studies, leptin levels may be
marginally higher in schizophrenia (g=0.164, 95% CI -0.014-0.341, p=0.07, Q=217,
p<0.01), particularly when one outlier was removed (g=0.196, 95% CI 0.210-0.370,
p=0.02) and when we included the smallest effect size from studies with multiple
comparisons (g=0.318, 95% CI 0.125-0.510, p=0.001). Leptin levels were higher in
multi-episode schizophrenia (g=0.245, 95% CI 0.058-0.433, p=0.01) and females
(g=0.557 95% CI 0.16-0.954, p=0.006). Subgroup analyses revealed leptin levels
may be higher in participants taking second-generation antipsychotics compared to
controls. Multivariate meta-regression demonstrated a lower percentage of males
(beta=-0.0064, 95% CI -0.0129 to -0.0002, p=0.05), but not BMI, moderated the
results. CONCLUSION: Our results suggest that schizophrenia is associated with
increased blood leptin levels compared to controls, which may not be entirely
attributable to antipsychotic medication or BMI. Other illness related and
lifestyle choices may play a pivotal role.
PMID- 26444589
TI - Controlled immobilization of His-tagged proteins for protein-ligand interaction
experiments using Ni2+-NTA layer on glass surfaces.
AB - Gold surfaces functionalized with nickel-nitrilotriacetic acid (Ni2+-NTA) as self
assembled monolayers (SAM) to immobilize histidine (His)-tagged biomolecules are
broadly reported in the literature. However, the increasing demand of using
microfluidic systems and biosensors takes more and more advantage on silicon
technology which provides dedicated glass surfaces and substantially allows cost
and resource savings. Here we present a novel method for the controlled oriented
immobilization of His-tagged proteins on glass surfaces functionalized with a
Ni2+-NTA layer. Exemplarily, the protein pattern morphology after immobilization
on the Ni2+-NTA layer of His6-tagged soluble receptor for advanced glycation
endproducts (sRAGE) was investigated and compared to non-oriented immobilization
of sRAGE on amino SAM by using scanning electron microscopy (SEM). Moreover, we
demonstrated interaction of immobilized sRAGE with three structurally different
ligands, S100A12, S100A4, and glycated low density lipoproteins (glycLDL), by
means of peak-force tapping atomic force microscopy (PF-AFM). We showed a clear
discrimination of different protein-ligand orientations by differential height
measurements.
PMID- 26444590
TI - Analysis of microcirculation measurements by novice users trained by a
standardized interactive tutorial: An inter-observer variability study.
AB - Excessive time for analysis may impede microcirculatory studies with large
amounts of video data. Engaging more personnel in the analyses seems to be a
rational approach in that scenario and could shorten the time-interval between
capturing images and obtaining results. Our hypothesis was that novice users
would be able to determine standard microcirculatory parameters using a semi
automated software with an acceptable degree of variability after participating
in a standardized interactive training session. 14 volunteers were included in
the study. All volunteers analyzed separately the same sample video after the
training. The kappa statistic was calculated for the primary outcome parameter
microvascular flow index (MFI) within small and large vessels and indicated a
fair level of agreement in the results of the novice users. A standardized
interactive tutorial can be useful to teach microcirculatory analysis in
previously untrained subjects.
PMID- 26444591
TI - Influence of blood pressure variability on the life of arteriovenous fistulae in
maintenance hemodialysis patients.
AB - BACKGROUND: Although numerous risk factors for arteriovenous fistulae (AVF)
dysfunction have been identified, these risk factors do not explain all cases of
AVF dysfunction. Because of the importance of blood pressure variability (BPV) in
vascular injury, the predictive value of BPV for AVF dysfunction, was evaluated
in this prospective cohort study. METHODS: Twenty-four-hour BP monitoring at the
intervals of dialysis was recorded every 3 months in 137 patients. The expression
of smooth muscle actin (SMA) and the infiltration of mononuclear cells and T
lymphocytes were determined by immunohistochemistry on the specimens of fistula
vessels. RESULTS: Eighteen patients developed AVF dysfunction. Cox proportional
hazards multivariate analysis revealed a significant relationship between fistula
dysfunction and daytime systolic-BPV (d-SBPV), nighttime systolic-BPV (n-SBPV),
diabetes mellitus, and initial venous diameter. Patients with AVF dysfunction
were observed to have increased SMA expression and more infiltration of
inflammatory cells in venous walls compared with the controls. A significant
correlation between SBPV and the infiltration of CD68-positive cells was
observed. CONCLUSIONS: Our study showed that the degrees of SBPV were
significantly associated with the risk of AVF dysfunction. Potentially, the
increase of SBPV will aggravate venous wall inflammation and may play a role in
AVF dysfunction.
PMID- 26444593
TI - Measurement of platelet aggregation functions using whole blood migration ratio
in a microfluidic chip.
AB - Platelets play a major role in maintaining endothelial integrity and hemostasis.
Of the various soluble agonists, ADP is an important in vivo stimulus for
inducing platelet aggregation. In this study, a simple, rapid, and affordable
method was designed for testing bleeding time (BT) and platelet aggregation with
a two-channel microfluidic chip. Whole blood migration ratio (MR) from a
microchip system was evaluated in comparison to the closure time (CT) from PFA
100 assays (Siemens, Germany) and CD62P expression on platelets. To induce
platelet aggregation, a combination of collagen (1.84 mg/ml) and ADP (37.5 mg/ml)
were used as agonists. After adding the agonists to samples, whole blood MR from
the microchip system was measured. The outcome of the assessment depended on
reaction time and agonist concentration. MR of whole blood from the microchip
system was significantly correlated with CT from PFA-100 (r = 0.61, p < 0.05, n
= 60). In addition, MR was negatively correlated with CD62P expression (r =-0.95,
p < 0.05, n = 60). These results suggest that the measurement of MR using
agonists is an easy, simple and efficient method for monitoring platelet
aggregation in normal and ADP-receptors defective samples, along with the BT
test. Thus, usage of the current microfluidic method could expand to diverse
applications, including efficacy assessments in platelet therapy.
PMID- 26444594
TI - Perfusion quantification of vascular malformations using contrast-enhanced
ultrasound (CEUS) with time intensity curve analysis before and after treatment:
First results.
AB - AIM: Aim of this pilot-study was to quantify perfusion changes of vascular
malformations before and after the first interventional treatment using contrast
enhanced ultrasound (CEUS). MATERIAL AND METHODS: 29 patients (10 male, 19
female) between 6 and 63 years (mean 28.1 years) with 12 arterio-venous (AVM) and
17 venous malformations (VM) were examined before and after their first
percutaneous interventional treatment. CEUS was performed with a 2.4 ml bolus
injection of sulfur-hexafluorid microbubbles, and a 6-9 MHz mulitfrequency
transducer. A 60 sec cine sequence was recorded and regions of interest (10 mm*30
mm) were defined in the centre, and the margins of the vascular malformation as
well as in the surrounding healthy tissue. Time Intensity Curves (TIC) were
analysed, and Time to Peak (TTP) as well as Area under the Curve (AUC) were
calculated. RESULTS: For VM there was a significant perfusion difference (p <
0.05) in AUC between centre and the surrounding tissue before (323.1 vs. 130.4
rU) and after treatment (331.0 vs. 106.9 rU). There was no significant difference
for TTP in ROIs of VM (19.1 vs. 26.5 sec). After the treatment there was a
significant decrease in AUC for all three regions in AVMs, and an increase in TTP
for AVM. However TTP for AVM in the centre ROI still remained shorter than in the
surrounding tissue even after therapy (20.9 vs. 25.4 sec). CONCLUSION: CEUS with
TIC analysis is a promising imaging method for the evaluation of perfusion before
and after percutaneous treatment of vascular malformations. AUC decrease
indicates therapy-induced changes in perfusion of VM whereas an increase in TTP
shows therapy-related changes in AVM.
PMID- 26444595
TI - Imaging of idle breast implants with ultrasound-strain elastography- A first
experimental study to establish criteria for accurate imaging of idle implants
via ultrasound-strain elastography.
AB - AIM: To investigate whether there are fundamental sonographic and elastographic
criteria to precisely assess different surfaces and fillings of idle breast
implants and to determine their most distinctive parameters. This was a
comparative study of different unused breast implant materials, neighter in
animals nor in humans. This knowledge should be transferred in vivo to develop an
objective measurement tool. METHODS: Nine idle breast implants-silicone and
polyurethane (PU)-were examined in an experimental study by using ultrasound B
mode with tissue harmonic imaging (THI), speckle reduction imaging (SRI, level 0
4), cross-beam (CB, low, medium, high), photopic and the colour coded ultrasound
strain elastography with a multifrequency probe (9-15 MHz).Using a standardised
protocol the implants' centre as well as the edge were analysed by one
experienced examiner. Two independent readers performed analysis and evaluation.
For image interpretation a score was created (score 0:inadequate image, score
5:best image quality). RESULTS: The highest score result for the centre was
achieved by using ultrasound with B-mode in addition with CB level medium, SRI
level 2, THI and photopic (mean:3.22+/-SD:1.56), but without any statistic
significant difference (t-value = 0.71). With elastography the implants' edge in
general was represented without disruptive artefacts (3.89+/-0.60) with statistic
significant difference (t-value = 5.29). Implants filled with inner cohesive
silicone gel II degrees showed best imaging conditions for their centre via
ultrasound (5+/-0) as well as for their edge via elastography (4.50+/-0.71).
CONCLUSION: Ultrasound-strain elastography and high resolution ultrasound
represent a valuable measurement tool to evaluate different properties of idle
breast implants. These modified ultrasound examinations could be an additional
help for clinical investigations and be correlated with Baker's Classification.
PMID- 26444592
TI - Impaired blood rheology is associated with endothelial dysfunction in patients
with coronary risk factors.
AB - To investigate the relationship between blood rheology and endothelial function
in patients with coronary risk factors, brachial arterial flow-mediated
vasodilatation (FMD), an index of endothelial function and blood passage time
(BPT), an index of blood rheology, and fasting blood cell count, glucose
metabolism, and plasma fibrinogen, lipid, C-reactive protein, and whole blood
viscosity levels were measured in 95 patients with coronary risk factors and 37
healthy controls. Brachial arterial FMD after reactive hyperemia was assessed by
ultrasonography. BPT was assessed using the microchannel method. In healthy
controls, BPT significantly correlated with FMD (r = - 0.325, p < 0.05), HDL
cholesterol (r = - 0.393, p < 0.05), body mass index (BMI; r = 0.530, p <
0.01), and plasma fibrinogen concentration (r = 0.335, p < 0.05). In a
multivariate regression analysis adjusted for all clinical variables, BPT
remained significantly associated with BMI and fibrinogen, but not with FMD, in
healthy controls. In patients with coronary risk factors, BPT significantly
correlated with FMD (r = - 0.331, p < 0.01), HDL cholesterol (r = - 0.241, p <
0.05), BMI (r = 0.290, p < 0.01), hematocrit (r = 0.422, p < 0.001), white
blood cell count (r = 0.295, p < 0.01), platelet count (r = 0.204, p < 0.05),
and insulin (r = 0.210, p < 0.05). In a multivariate regression analysis
adjusted for all clinical variables, BPT remained strongly associated with FMD
and hematocrit in patients with coronary risk factors. These data indicate that
BPT is closely associated with FMD in patients with coronary risk factors and
suggest that the measurement of blood rheology using the microchannel method may
be useful in evaluating brachial arterial endothelial function as a marker of
atherosclerosis in these patients.
PMID- 26444596
TI - Contrast enhanced ultrasound (CEUS) - an unique monitoring technique to assess
microvascularization after buried flap transplantation.
AB - OBJECTIVE: Incidence of patients requiring complex soft tissue or osseous
reconstruction has dramatically increased. However most of the monitoring systems
have limitations in tissue penetration and are not able to detect microvascular
complications after transplantation of so-called buried-flaps, that have no
contact to the surface.Aim of the study was to assess contrast enhanced
ultrasound (CEUS) as monitoring tool after buried flap transplantations. METHODS:
20 patients were examined after buried flap transplantation using CEUS.
Quantitative perfusion analysis (TIC) was performed with an integrated perfusion
software using stored cine-loops. Two perfusion-parameters, time to PEAK (TtoPk)
and area under the curve (Area), were evaluated using TIC analysis. RESULTS:
Minor complications were observed in 3 patients. In these patients a delayed
contrast agent wash-in and wash-out was observed. Additionally the perfusion
values TtoPk (sec.) and Area (relative Units) were clearly different in the
patients with minor complications: TtoPk: 32.0 sec; Area 425.5 rU (without
complication), TtoPk: 38.6 sec.; Area: 18.3 rU (wound healing disturbance) and
TtoPk: 14.4 sec.; Area: 105.9 rU (hematoma). CONCLUSION: As CEUS can assess
microvascularization almost depth-independent, CEUS is an unique method to assess
global flap perfusion after buried flap transplantation.
PMID- 26444597
TI - The effect of centrifugation at various g force levels on rheological properties
of rat, dog, pig and human red blood cells.
AB - Laboratory investigations often require centrifugation of blood samples for
various erythrocyte tests. Although there is a lack of data about the effect of
centrifugation at various g force levels on erythrocyte rheological properties.
We aimed to investigate the effect of a 10-minute centrifugation at 500, 1000 or
1500 g at 15 degrees C of rat, dog, pig and human venous (K3-EDTA, 1.5 mg/ml)
blood samples. Hematological parameters, erythrocyte deformability, cell membrane
stability, osmotic gradient ektacytometry (osmoscan) and erythrocyte aggregation
were determined. Hematological and erythrocyte deformability parameters showed
interspecies differences, centrifugation caused no significant alterations. Cell
membrane stability for human erythrocytes centrifuged at higher g level showed
less decrease in deformability. Osmoscan O min parameter showed slight elevation
in dog centrifuged aliquots. Erythrocyte aggregation parameters changed
unexpectedly. Rat and dog erythrocyte aggregation indices significantly dropped
in centrifuged aliquots. Pig erythrocyte aggregation indices increased
significantly after centrifugation. Human erythrocyte aggregation was the most
stable one among the investigated species. The used centrifugation protocols
caused the largest alterations in erythrocyte aggregation in a controversial way
among the investigated species. On the other hand, erythrocyte deformability
parameters were stable, cell membrane stability and osmoscan data show minor
shifts.
PMID- 26444598
TI - Assessment of renal perfusion with contrast-enhanced ultrasound: Preliminary
results in early diabetic nephropathies.
AB - OBJECTIVE: We performed a prospective study to evaluate the value of contrast
enhanced ultrasound (CEUS) in quantitative evaluation of renal cortex perfusion
in patients suspected of early diabetic nephropathies (DN), with the estimated
GFR (MDRD equation) as the gold standard. METHODS: The study protocol was
approved by the hospital review board; each patient gave written informed
consent. Our study included 46 cases (21 males and 25 females, mean age 55.6 +/-
4.14 years) of clinical confirmed early DN patients. After intravenous bolus
injection of 1 ml sulfur hexafluoride microbubbles of ultrasound contrast agent,
real time CEUS of renal cortex was performed successively using a 2-5 MHz convex
probe. Time-intensity curves (TICs) and quantitative indexes were created with
Qlab software. Receiver operating characteristic (ROC) curves were used to
predict the diagnostic criteria of CEUS quantitative indexes, and their
diagnostic efficiencies were compared with resistance index (RI) and peak
systolic velocity (PSV) of renal segmental arteries by chi square test. Our
control group included forty-five healthy volunteers. Difference was considered
statistically significant with P < 0.05. RESULTS: Changes of area under curve
(AUC), derived peak intensity (DPI) were statistically significant (P < 0.05).
DPI less than 12 and AUC greater than 1400 had high utility in DN, with 71.7% and
67.3% sensitivity, 77.8% and 80.0% specificity. These results were significantly
better than those obtained with RI and PSV which had no significant difference in
early stage of DN (P > 0.05). CONCLUSIONS: CEUS might be helpful to improve early
diagnosis of DN by quantitative analyses. AUC and DPI might be valuable
quantitative indexes.
PMID- 26444599
TI - Behaviour of the neutrophil to lymphocyte ratio in young subjects with acute
myocardial infarction.
AB - In the last years the neutrophil to lymphocyte ratio (NLR) has been examined in
cardiovascular disorders and in particular in coronary artery disease and acute
myocardial infarction (AMI). Now we examined this parameter in subjects with
juvenile myocardial infarction at the initial stage and after 3 and 12 months. We
enrolled 123 young subjects (112 men and 11 women, mean age 39.4 +/- 5.8 yrs)
with AMI. The time interval between the AMI onset and the investigation was 13 +/
7 days. The mean value of NLR observed in young AMI subjects was significantly
increased compared to normal controls (N = 1.817 +/- 0.711; young AMI subjects =
2.376 +/- 0.873, p < 0.0001). NLR does not discriminate STEMI (2.427 +/- 0.878)
and non STEMI (2.392 +/- 0.868) or diabetics (2.604 +/- 1.000) and non diabetics
(2.324 +/- 0.853), but it differentiates smokers (2.276 +/- 0.853) and non
smokers (2.837 +/- 1.072). NLR at the initial stage is not correlated with the
number of cardiovascular risk factors or with the extent of the coronary disease.
In this study we found a significant decrease of neutrophil count at 3 and 12
months later AMI without any significant variation of lymphocyte and consequently
we observed a decrease in NLR at these two intervals of time in comparison with
the initial stage. Despite some limitations present in this study, it is
interesting to underline that also in juvenile myocardial infarction this low
cost haematological marker may be considered together with other inflammatory
indicators.
PMID- 26444600
TI - Influence of shear stress on erythrocyte aggregation.
AB - Shear stress is known to induce platelet activation and aggregation. The red
blood cell (RBC) aggregation test requires the application of shear stress for
the cells to disaggregate for initialization. We tested the hypothesis that
applying shear stress may activate platelets, which can influence RBC
aggregation. The present study used a commercial microchip-based aggregometer
(RheoSCan-AnD300) with a rotating stirrer for RBC disaggregation. Whole blood
samples were exposed to different magnitudes of shear stress with various
shearing times. As the rotational speed was increased up to 2800 rpm, the RBC
aggregation index (AI) of the whole blood increased by up to 30% (p < 0.05),
whereas that of the platelet-excluded blood samples did not show any apparent
alteration. The AI also increased in proportion with the stirring time. The data
suggest that high shear stress affects RBC aggregation through shear-induced
platelet aggregation.
PMID- 26444601
TI - Elevated whole blood viscosity in patients with lumbar disc herniation.
AB - BACKGROUND: Various vascular risk factors such as smoking, obesity, and diabetes
mellitus are associated with hyperviscosity and lumbar disc herniation (LDH).
However, the changes of viscosity in LDH have not been examined. AIMS: The
present study was to elucidate 1) the rheological parameter levels in patients
with LDH, 2) the risk factors that were related to rheological parameters.
METHODS: Our study evaluated the rheological parameters in 307 cases with LDH and
in 307 control subjects. Multiple linear regression analysis was conducted to
assess the significant factors for whole blood viscosity (WBV) at low shear rate.
RESULTS: LDH patients had markedly lower physical activity and significantly
higher WBV 3 s-1 compared with non-LDH subjects (p < 0.001). Moreover, WBV (3 s
1) tended to increase as physical activity decreased. Multiple linear regression
analysis revealed that reduced physical activity was a significant factor
contributing to elevated WBV (3 s-1). CONCLUSIONS: WBV (3 s-1) is elevated in
patients with LDH. In addition, reduced physical activity is a significant factor
for WBV (3 s-1). Further studies are warranted to determine the role of WBV (3 s
1) in LDH.
PMID- 26444602
TI - Vascular phases in imaging and their role in focal liver lesions assessment.
AB - The incidental finding of a liver lesion with basic ultrasound is one of the most
common clinical issues. Some of the liver lesions which present typical
morphological B-mode features (e.g. cysts, typically localized focal fatty
sparing/accumulations, hyperechoic hemangiomas) can be easily diagnosed by
conventional ultrasound without the need of further diagnostic procedures. Others
frequently necessitate further investigation with contrast-enhanced imaging
techniques or biopsy in order to differentiate benign from malignant lesions and
obtain a final diagnosis. This paper will discuss differences between vascular
phases of different cross-sectional contrast-enhanced methods, as well as their
subsequent benefits for focal liver lesions (FLLs) assessment, adding also a
particular emphasis on small FLLs detection and characterization.
PMID- 26444603
TI - Pfaffia paniculata extract improves red blood cell deformability in sickle cell
patients.
AB - The aim of the present study was to test the effects of Pfaffia paniculata (PP)
extract on the red blood cell (RBC) rheological properties of patients with
sickle cell disease (SCD) and healthy (AA) individuals. Blood from 7 SCD and 4 AA
individuals were collected in EDTA tubes. Washed RBCs were incubated with various
concentration of PP extract: 0.0, 0.2 or 0.5 mg/ml of PP solution for 5 hrs at 37
degrees C. RBC deformability was measured by ektacytometry at 9 shear stresses
ranging from 0.3 to 30 Pa, and RBC aggregation properties were determined by
laser-backscattered techniques. Because RBCs from SCD patients are fragile, a
stability test was also performed to test for the fragility of RBC exposed to a
constant shear stress (70 Pa) for 10 min. While RBC deformability was not
improved by the use of PP extract in AA, we noted an improvement of this
parameter in patients with SCD between the 0.0 and 0.5 mg/ml conditions. In
contrast to AA RBCs, the fragility of SCD RBCs was not affected by PP extract. In
conclusion, this study demonstrates the beneficial effects, in-vitro, of PP
extract on the RBC deformability of SCD patients, notably at high shear stress (a
shear stress condition usually found in capillaries).
PMID- 26444604
TI - Chronic intermittent hypoxia versus continuous hypoxia: Same effects on
hemorheology?
AB - Although both chronic intermittent hypoxia (CIH) and chronic continuous hypoxia
(CCH) have effects on hemorheology, we do not know whether their roles are the
same. In this study, we explored the effect of simulated-apnea CIH on
hemorheology in experimental rats and compared with the effect of CCH. 45 adult
SD rats were randomly divided into the normoxic control group, CCH and CIH
groups. CIH rats were given nitrogen and air alternately for 8 hours per day and
the experiment lasted for 5 weeks. The control group were placed in the normoxia
animal chambers, and the CCH rats were housed in the same chambers which were
continuously given normobaric hypoxia (FiO2 = 10%). After the preparations, the
blood samples were taken and the hemorheology were determined. Compared with
control group, the whole blood apparent viscosity, plasma viscosity, hematocrit,
erythrocyte aggregation index and electrophoresis index, platelet aggregation
rate and fibrinogen significantly increased in CIH group and CCH group. The whole
blood viscosity, plasma viscosity, hematocrit and fibrinogen values were much
higher in CCH group than in CIH group. However, there was not significantly
difference in RBC deformation index or rigidity index among the three groups and
no significantly differences were found in the effects on RBC rheological
property between CIH and CCH. Our results suggest that intermittent hypoxia and
continuous hypoxia increase whole blood viscosity, impair the functions of red
blood cells and promote the platelet aggregation in model rats. Moreover, CCH had
a greater effect on blood rheology than CIH.
PMID- 26444605
TI - Association of whole blood viscosity with non-alcoholic fatty liver disease.
AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an independent risk
factor for increased cardiovascular disease. Altered hemorheological parameters
have also been shown to play a crucial role in atherogenesis. Moreover, increased
viscosity is observed in insulin resistance, metabolic syndrome, hypertension,
diabetes, ischemic heart disease, and stroke. A recent study confirmed that whole
blood viscosity (WBV) is a predictor of cardiovascular events. AIMS: This study
aimed to investigate the association of WBV with NAFLD. METHODS: In this cross
sectional study, we investigated the relationship between WBV and NAFLD in 1329
subjects (962 men and 367 women) in a general health examination. RESULTS: WBV at
low shear stress was elevated in patients with NAFLD. In addition, the prevalence
of metabolic syndrome and NAFLD increased as WBV quartiles increased both in men
and in women. Multiple regression analysis further identified WBV as an
independent and significant determinant for NAFLD. CONCLUSIONS: The findings
showed that WBV at low shear stress is increased in NAFLD. Moreover, WBV at low
shear stress is independently associated with NAFLD even after adjusting other
cardiovascular risk factors.
PMID- 26444606
TI - Serial assessments of microvascular obstruction by contrast-enhanced magnetic
resonance predict contractile recovery and clinical outcome after reperfused
acute myocardial infarction.
AB - AIMS: The purpose of the study was to investigate, using cardiac magnetic
resonance (CMR), the presence and time course of microvascular obstruction (MO)
in patients with acute myocardial infarction (AMI), and to test its relationship
with cardiac remodeling and clinical outcomes. METHODS AND RESULTS: 53 patients
with AMI and successful percutaneous reperfusion underwent CMR examination at
four separate timepoints: within the first 48 hours, at 10 days, at six and
twelve months after infarction. MO was quantified immediately (early imaging) and
10 minutes (late imaging) after contrast administration in each session. The
extent of MO decreased from early to late imaging at both the first and the
second CMR exam (p<=0.001). Early MO was absent in 18(36%) patients both at 48
hours and 10 days after AMI. At 1 year follow-up, LVEF in these patients improved
to normal (median = 62% (53-70)). Early MO was present in the first but not in
the second CMR in 13 (26%) patients; LVEF at one year in these patients reached a
median = 52% (47-61). Finally, Early MO was present in both exams in 19 (38%)
patients, who at 1 year after infarction had a LVEF of median = 49% (42-54,
P<=0.001 across groups). The time course of MO was a predictor of prognosis upon
Kaplan-Meier analysis (P = 0.035). The presence of MO at 10 days after AMI was
associated with a higher risk of MACE during a 5-years follow-up. CONCLUSIONS:
The presence of MO within 48 hours after AMI, and its time course in the
following ten days, provides complementary information on both functional
myocardial recovery and long-term outcome.
PMID- 26444607
TI - Wall shear stress in the human eye microcirculation in vivo, segmental
heterogeneity and performance of in vitro cerebrovascular models.
AB - Wall shear stress (WSS) is a very important hemodynamic parameter implicated in
many physiological and pathological phenomena. In order to study these phenomena,
it is more convenient to use in vitro models before testing on animals and
humans. Dynamic in vitro cerebrovascular models are considered capable of
simulating the in vivo hemodynamic conditions, but only few of them seem to meet
the criteria for this task. It is now clear that in the human eye
microcirculation a significant pulsation exists at the pre-capillary arterioles
with average WSS values more than twice those in the venular side, for the same
diameters. WSS heterogeneity is in support of segmental heterogeneity i.e. the
endothelial phenotypic and functional difference among arterioles, capillaries
and venules. In this review paper, the importance of WSS is described in detail
and two more microvascular segments are proposed: a pre-capillary arteriolar and
a post-capillary venular segment. The accurate hemodynamic simulation in all
microvascular segments seems to be a prerequisite step in the development of
dynamic in vitro blood brain barrier (BBB) models and microfluidic platforms on
chip. Endothelial cells in the cardiovascular system seem to have sophisticated
role acting like cardiovascular processing sensors (CPSs).
PMID- 26444608
TI - Conjunctival microvascular hemodynamics following vaso-occlusive crisis in sickle
cell disease.
AB - Painful vaso-occlusive crisis (VOC) is the clinical hallmark of sickle cell
disease (SCD). Microcirculatory hemodynamic changes following painful VOC may be
indicative of future development of VOC events in subjects with SCD. The purpose
of the present study was to determine alterations in conjunctival microvascular
hemodynamics during non-crisis state in SCD subjects with a history of VOC.
Conjunctival microcirculation imaging was performed to measure conjunctival
diameter (D) and axial blood velocity (V) in 10 control and 30 SCD subjects. SCD
subjects were categorized into two groups based on their history of VOC within a
2-year period before imaging (with or without VOC-H) and also based on whether
there was progression in the rate of VOCs during a 2-year period following
imaging as compared to before imaging (with or without VOC-P). Conjunctival V was
significantly higher in SCD subjects with VOC-H than in both control subjects and
SCD subjects without VOC-H (P<=0.03). Conjunctival V was also significantly
higher in SCD subjects with VOC-P compared with control subjects and SCD subjects
without VOC-P (P<=0.03). Assessment of the conjunctival microcirculation may be
useful for understanding hemodynamic changes that lead to VOC events in SCD
subjects.
PMID- 26444609
TI - High red blood cell distribution width is associated with the metabolic syndrome.
AB - OBJECTIVES: High values of Red Blood Cell Distribution Width (RDW) have been
associated with adverse outcome in various clinical settings. The mechanism
behind this association is not clear. The Metabolic Syndrome (MetS) is a chronic
inflammatory disorder that increases the risk for cardiovascular disease and
death. The aim of our study was to evaluate the association between high RDW and
the MetS in a relatively large cohort of patients. METHODS: A cohort of 3,529
consecutive patients undergoing coronary angiography was used to evaluate the
association between RDW and the MetS. The association was assessed by using a
logistic regression. Cox's regression analysis was used to evaluate the impact of
RDW on long term mortality. RESULTS: The mean age was 65 years (range 24-97),
with 27% women. Overall, 30% were diagnosed with metabolic syndrome. The
prevalence of MetS was 29% in patients with RDW <14% and 34% in patients with RDW
>=14% (P = 0.003).Using multivariate analysis, RDW values above 14% were
independently associated with MetS (odds ratio 1.2 [95% CI 1.0-1.4], P = 0.043).
Among all the criteria of the metabolic syndrome, hypertension, elevated glucose
levels and abdominal obesity were associated with high RDW, with hypertension
being the strongest criteria, with an increased risk of 1.8 fold ([95% CI 1.5
2.1]; P = 0.001). During follow up (1614 +/- 709 days, 2-2763 days), long term
mortality was 8% in the low RDW group and 28% in the high RDW group (p < 0.001).
CONCLUSION: RDW >=14% is independently associated with higher rates of metabolic
syndrome and long-term all-cause mortality.
PMID- 26444610
TI - Importance of methodological standardization for the ektacytometric measures of
red blood cell deformability in sickle cell anemia.
AB - Red blood cell (RBC) deformability is severely decreased in patients with sickle
cell anemia (SCA), which plays a role in the pathophysiology of the disease.
However, investigation of RBC deformability from SCA patients demands careful
methodological considerations. We assessed RBC deformability by ektacytometry
(LORRCA MaxSis, Mechatronics, The Netherlands) in 6 healthy individuals and 49
SCA patients and tested the effects of different heights of the RBC diffraction
patterns, obtained by altering the camera gain of the LORRCA, on the result of
RBC deformability measurements, expressed as Elongation Index (EI). Results
indicate that the pattern of RBCs from control subjects adopts an elliptical
shape under shear stress, whereas the pattern of RBCs from individuals with SCA
adopts a diamond shape arising from the superposition of elliptical and circular
patterns. The latter represent rigid RBCs. While the EI measures did not change
with the variations of the RBC diffraction pattern heights in the control
subjects, we observed a decrease of EI when the RBC diffraction pattern height is
increased in the SCA group. The differences in SCA EI values measured at 5 Pa
between the different diffraction pattern heights correlated with the percent of
hemoglobin S and the percent of sickled RBC observed by microscopy. Our study
confirms that the camera gain or aperture of the ektacytometer should be used to
standardize the size of the RBC diffraction pattern height when measuring RBC
deformability in sickle cell patients and underscores the potential clinical
utility of this technique.
PMID- 26444611
TI - Quantifying local characteristics of velocity, aggregation and hematocrit of
human erythrocytes in a microchannel flow.
AB - The effect of erythrocyte aggregation on blood viscosity and microcirculatory
flow is a poorly understood area of haemodynamics, especially with relevance to
serious pathological conditions. Advances in microfluidics have made it possible
to study the details of blood flow in the microscale, however, important issues
such as the relationship between the local microstructure and local flow
characteristics have not been investigated extensively. In the present study an
experimental system involving simple brightfield microscopy has been successfully
developed for simultaneous, time-resolved quantification of velocity fields and
local aggregation of human red blood cells (RBC) in microchannels. RBCs were
suspended in Dextran and phosphate buffer saline solutions for the control of
aggregation. Local aggregation characteristics were investigated at bulk and
local levels using statistical and edge-detection image processing techniques. A
special case of aggregating flow in a microchannel, in which hematocrit gradients
were present, was studied as a function of flowrate and time. The level of
aggregation was found to strongly correlate with local variations in velocity in
both the bulk flow and wall regions. The edge detection based analysis showed
that near the side wall large aggregates are associated with regions
corresponding to high local velocities and low local shear. On the contrary, in
the bulk flow region large aggregates occurred in regions of low velocity and
high erythrocyte concentration suggesting a combined effect of hematocrit and
velocity distributions on local aggregation characteristics. The results of this
study showed that using multiple methods for aggregation quantification, albeit
empirical, could help towards a robust characterisation of the structural
properties of the fluid.
PMID- 26444612
TI - MicroRNA-761 inhibits Angiotensin II-induced vascular smooth muscle cell
proliferation and migration by targeting mammalian target of rapamycin.
AB - Aberrant vascular smooth muscle cell (VSMC) proliferation and migration are a
major pathological phenomenon in vascular disease characterized by intimal
thickening. The important role of the mammalian target of rapamycin (mTOR)
signaling in VSMC proliferation has been previously reported. Consequently, down
regulation of mTOR pathway may be an effective way of controlling excessive VSMC
proliferation. Since microRNAs (miRNA) are newly emerging regulators of virtually
all the biological processes including cellular proliferation, miRNAs targeting
mTOR pathway may be utilized to suppress aberrant VSMC proliferation during
pathologic conditions. Thus, in the present study, we screened miRNAs targeting
mTOR, and we identified miR-761 as a new mTOR targeting miRNA. Luciferase assay
using luciferase vector containing 3'UTR of mTOR indicated that miR-761 directly
targets mTOR mRNA leading to suppression of mTOR protein expression. Our data
also indicate that miR-761 expression decreases during angiotensin II (AngII)
induced proliferation of VSMCs, and exogenous miR-761 delivery effectively
inhibit the AngII-induced VSMC proliferation. Additionally, the results of
migration tests demonstrate that down-regulation of mTOR using exogenous miR-761
suppresses AngII-induced migration of VSMCs as well. Taken together, the present
study provided evidence that miR-761 can be a potent anti-proliferative agent for
vascular diseases such as atherosclerosis and restenosis, and warrants further
studies to validate the effectiveness of miR-761 in vivo.
PMID- 26444613
TI - The interaction of human macrophage subsets with silicone as a biomaterial.
AB - Silicones are widely used as biomaterials for medical devices such as
extracorporeal equipments. However, there is often conflicting evidence about
their supposed cell- and histocompatibility. Macrophages could mediate silicone
induced adverse responses such as foreign body reaction and fibrous
encapsulation. The polarization behaviour of macrophages could determine the
clinical outcome after implantation of biomaterials. Induction of classically
activated macrophages (CAM) may induce and support uncontrolled inflammatory
responses and undesired material degradation. In contrast, polarization into
alternatively activated macrophages (AAM) is assumed to support healing processes
and implant integration.This study compared the interaction of non-polarized
macrophages (M0), CAM, and AAM with commercially available tissue culture
polystyrene (TCP) and a medical grade silicone-based biomaterial, regarding the
secretion of inflammatory mediators such as cytokines and chemokines. Firstly, by
using the Limulus amoebocyte lysate (LAL) test the silicone films were shown to
be free of soluble endotoxins, which is the prerequisite to investigate their
interaction with primary immune cells. Primary human monocyte-derived macrophages
(M0) were polarized into CAM and AAM by addition of suitable differentiation
factors. These macrophage subsets were incubated on the materials for 24 hours
and their viability and cytokine secretion was assessed. In comparison to TCP,
cell adhesion was lower on silicone after 24 hours for all three macrophage
subsets. However, compared to TCP, silicone induced higher levels of certain
inflammatory and chemotactic cytokines in M0, CAM, and AAM macrophage
subsets.Conclusively, it was shown that silicone has the ability to induce a pro
inflammatory state to different magnitudes dependent on the macrophage subsets.
This priming of the macrophage phenotype by silicone could explain the incidence
of severe foreign body complications observed in vivo.
PMID- 26444614
TI - Human microvascular endothelial cells displaying reduced angiogenesis and
increased uptake of lipids during in vitro culture.
AB - Human microvascular ECs from the neonatal foreskin of two donors purchased from
one distributor were used in an angiogenesis assay under the same culture
conditions. Different angiogenic potency was apparent in these two batches (ECang
and ECnon-ang). During the cultivation period of three weeks, ECang ran through
all stages of angiogenesis starting from proliferation to migration up to the
formation of three-dimensional capillary-like structures. Despite of expression
of endothelial markers, ECnon-ang showed excessive intracellular storage of
lipids in form of multilamellar bodies and decreased angiogenic potency in
contrast to its counterpart, ECang. Results indicate that lipid metabolism
differs in ECang versus ECnon-ang. This study points up that these differences
are based on the different donors and presents a novel and valuable model for the
study of mechanisms of atherosclerosis in endothelial cells in vitro.
PMID- 26444615
TI - Evaluation of the diagnostic accuracy of CEUS in children with benign and
malignant liver lesions and portal vein anomalies.
AB - OBJECTIVE: Comparison of the diagnostic findings of MRI, CT and CEUS in children
with benign and malignant and portal venous anomalies of the liver.
MATERIALS/METHODS: Retrospective analysis of the diagnostic findings of CEUS, MRI
and CT scans in 56 children (age 0-17 years) with a total of 60 benign and
malignant liver lesions and anomalies of the portal vein/perfusion. All patients
underwent CEUS using sulphur hexafluoride microbubbles and a multi-frequency
probe (1-5 MHz, 6-9 MHz). Cine-loops were stored up to 3 minutes. MRI was
performed in 38 lesions. CT was performed in 8 lesions. RESULTS: Out of the 56
patients 49 liver lesions (48 benign, 1 malignant), 9 anomalies of the portal
vein/perfusion and 2 of the biliary system were detected. 16/49 lesions were
analyzed histopathologically. Using CEUS, the characterization of the lesions was
possible in 45 out of 49 cases. In 32 cases, CEUS provided the exact diagnosis.
Only two benign lesions were falsely categorized as malignant.Findings of MRI and
CEUS were concordant in 84% of cases (n = 32/38). CEUS considered 1 benign lesion
to be malignant. 2 lesions were not detectable and in 3 lesions no definite
diagnosis was established using MRI.Findings of CT and CEUS were concordant in 5
of 8 cases. In 21 lesions CEUS as the only imaging modality was found to be
sufficient for diagnostics. CONCLUSION: Despite the restricted indications for
using CEUS in children, it offers a high diagnostic detection rate (93%) for
characterization of liver lesions and portal vein anomalies.
PMID- 26444616
TI - Polymeric inserts differing in their chemical composition as substrates for
dendritic cell cultivation.
AB - Dendritic cells (DC) contribute to immunity by presenting antigens to T cells and
shape the immune response by the secretion of cytokines. Due to their immune
stimulatory potential DC-based therapies are promising approaches to overcome
tolerance e.g. against tumors. In order to enforce the immunogenicity of DCs,
they have to be matured and activated in vitro, which requires an appropriate
cell culture substrate, supporting their survival expansion and activation.Since
most cell culture devices are not optimized for DC growth, it is hypothesized
that polymers with certain physicochemical properties can positively influence
the DC cultures. With the aim to evaluate the effects that polymers with
different chemical compositions have on the survival, the activation status, and
the cytokine/chemokine secretion profile of DC, their interaction with
polystyrene (PS), polycarbonate (PC), poly(ether imide) (PEI), and poly(styrene
co-acrylonitrile) (PSAN)-based cell culture inserts was investigated. By using
this insert system, which fits exactly into 24 well cell culture plates, effects
induced from the culture dish material can be excluded. The viability of
untreated DC after incubation with the different inserts was not influenced by
the different inserts, whereas LPS-activated DC showed an increased survival
after cultivation on PC, PS, and PSAN compared to tissue culture polystyrene
(TCP). The activation status of DC estimated by the expression of CD40, CD80,
CD83, CD86 and HLA-DR expression was not altered by the different inserts in
untreated DC but slightly reduced when LPS-activated DC were cultivated on PC,
PS, PSAN, and PEI compared to TCP. For each polymeric cell culture insert a
distinct cytokine profile could be observed.Since inserts with different chemical
compositions of the inserts did not substantially alter the behavior of DC all
insert systems could be considered as alternative substrate. The observed
increased survival on some polymers, which showed in contrast to TCP a
hydrophobic surface, could be beneficial for certain applications such as T cell
expansion and activation.
PMID- 26444617
TI - Recommendations for contrast enhanced ultrasound (CEUS) in free tissue transplant
monitoring.
AB - Complications rates after free flap transplantation still amount up to 5% .
Consequently a reliable monitoring system is of high importance in plastic and
reconstructive surgery. The following guidelines provide an overview of the
current opportunities for free flap planning and monitoring with ultrasound and
in particular with contrast enhanced ultrasound.
PMID- 26444618
TI - The asymmetric facial skin perfusion distribution of Bell's palsy discovered by
laser speckle imaging technology.
AB - Bell's palsy is a kind of peripheral neural disease that cause abrupt onset of
unilateral facial weakness. In the pathologic study, it was evidenced that
ischemia of facial nerve at the affected side of face existed in Bell's palsy
patients. Since the direction of facial nerve blood flow is primarily proximal to
distal, facial skin microcirculation would also be affected after the onset of
Bell's palsy. Therefore, monitoring the full area of facial skin microcirculation
would help to identify the condition of Bell's palsy patients. In this study, a
non-invasive, real time and full field imaging technology - laser speckle imaging
(LSI) technology was applied for measuring facial skin blood perfusion
distribution of Bell's palsy patients. 85 participants with different stage of
Bell's palsy were included. Results showed that Bell's palsy patients' facial
skin perfusion of affected side was lower than that of the normal side at the
region of eyelid, and that the asymmetric distribution of the facial skin
perfusion between two sides of eyelid is positively related to the stage of the
disease (P < 0.001). During the recovery, the perfusion of affected side of
eyelid was increasing to nearly the same with the normal side. This study was a
novel application of LSI in evaluating the facial skin perfusion of Bell's palsy
patients, and we discovered that the facial skin blood perfusion could reflect
the stage of Bell's palsy, which suggested that microcirculation should be
investigated in patients with this neurological deficit. It was also suggested
LSI as potential diagnostic tool for Bell's palsy.
PMID- 26444619
TI - Whole blood viscosity of preterm infants - differences to term neonates.
AB - Determination of shear stresses at given shear rates with the LS 300 allows
approximation of flow curves by mathematical models and to calculate viscosities
of non-Newtonian fluids across the entire physiological shear range. Particular
in preterm neonates, which in comparison to term neonates and adults have a
substantially lower mean arterial blood pressure (MAP), rheological blood
properties play a decisive role to maintain the perfusion. Whole blood viscosity
was measured in umbilical cord blood taken from 34 preterm neonates using the LS
300 viscometer. In addition aggregation index, plasma viscosity, hematocrit and
red blood cell (RBC) deformability was determined. The highest quality of
approximation of the flow curve of whole blood was achieved by the method of
Ostwald. Shear stresses of whole blood of preterm neonates were significantly
lower compared to term neonates at similar shear rates (velocity range 6.16 s-1
50 s-1). With hematocrit calculated to 0.40 the related exponent (n) of the
viscosity of preterm neonates (by Ostwald) showed a significant lower exponent
(n) (0.71 +/- 0.07) than term neonates (0.76 +/- 0.06). The highest quality of
approximation of the flow curve of plasma was achieved with the model of Ostwald
in preterm neonates as well as in term neonates. The viscosity of plasma
determined by Newton was lower for preterm neonates (0.89 +/- 0.19) than for term
neonates (1.04 +/- 0.16). Concurrent to term neonates the whole blood of preterm
neonates showed a very low aggregation index (term neonates 2.97 +/- 2.10;
preterm neonates 2.37 +/- 1.32) and preterm neonates showed higher RBC
deformability than term neonates. Because of the physiologically lower MAP and
the particular viscous properties of neonatal blood special attention should be
given when treating neonates with conventional blood products derived from adult
donors.
PMID- 26444620
TI - Determination of whole blood and plasma viscosity in term neonates by flow curve
analysis with the LS300 viscometer1.
AB - Determination of shear stresses at given shear rates allow approximation of flow
curves by mathematical models and to calculate viscosities of non-Newtonian
fluids. In term neonates, the mean arterial blood pressure (MAP) is markedly
below that of adults, therefore rheological properties of blood play an important
role in maintaining perfusion. Whole blood viscosity was measured in umbilical
cord blood taken from 62 term neonates using the LS 300 viscometer. Individual
parameters that influence the viscosity of whole blood were measured: red blood
cell (RBC) aggregation, plasma viscosity, hematocrit, and RBC deformability. The
flow curve of whole blood of neonates was approximated by the method of Ostwald
with the highest quality whereas in adults the best approximation was found by
the method of Casson. With hematocrits of 0.40, the viscosity of whole blood in
newborns approximated by Ostwald (9.84 +/- 5.12 mPa.s) was significantly lower
than that of adults (15.34 +/- 3.01 mPa.s). The aggregation index of the blood of
newborns was markedly lower (2.98 +/- 2.12) than in adults (14.63 +/- 3.50)
whereas RBC deformability was higher in neonates. The viscosity of plasma
determined by Ostwald revealed a lower exponent (n) in neonates (0.94 +/- 022)
compared to adults (1.01 +/- 0.12) and the viscosity determined by Newton was
lower in neonates (1.04 +/- 0.16 mPa.s) than in adults (1.19 +/- 0.07 mPa.s). The
flow curve of neonatal blood which is best approximated by the model of Ostwald
emphasizes its important viscous properties necessary for conditions with
physiologically low blood pressure.
PMID- 26444621
TI - Harvesting Nanocatalytic Heat Localized in Nanoalloy Catalyst as a Heat Source in
a Nanocomposite Thin Film Thermoelectric Device.
AB - This report describes findings of an investigation of harvesting nanocatalytic
heat localized in a nanoalloy catalyst layer as a heat source in a nanocomposite
thin film thermoelectric device for thermoelectric energy conversion. This device
couples a heterostructured copper-zinc sulfide nanocomposite for thermoelectrics
and low-temperature combustion of methanol fuels over a platinum-cobalt nanoalloy
catalyst for producing heat localized in the nanocatalyst layer. The possibility
of tuning nanocatalytic heat in the nanocatalyst and thin film thermoelectric
properties by compositions points to a promising pathway in thermoelectric energy
conversion.
PMID- 26444622
TI - Higher Retail Prices of Sugar-Sweetened Beverages 3 Months After Implementation
of an Excise Tax in Berkeley, California.
AB - OBJECTIVES: We assessed the short-term ability to increase retail prices of the
first US 1-cent-per-ounce excise tax on the distribution of sugar-sweetened
beverages (SSBs), which was implemented in March 2015 by Berkeley, California.
METHODS: In 2014 and 2015, we examined pre- to posttax price changes of SSBs and
non-SSBs in a variety of retailers in Berkeley and in the comparison cities
Oakland and San Francisco, California. We examined price changes by beverage,
brand, size, and retailer type. RESULTS: For smaller beverages (<= 33.8 oz),
price increases (cents/oz) in Berkeley relative to those in comparison cities
were 0.69 (95% confidence interval [CI] = 0.36, 1.03) for soda, 0.47 (95% CI =
0.08, 0.87) for fruit-flavored beverages, and 0.47 (95% CI = 0.25, 0.69) for SSBs
overall. For 2-liter bottles and multipacks of soda, relative price increases
were 0.46 (95% CI = 0.03, 0.89) and 0.49 (95% CI = 0.21, 0.77). We observed no
relative price increases for nontaxed beverages overall. CONCLUSIONS:
Approximately 3 months after the tax was implemented, SSB retail prices increased
more in Berkeley than in nearby cities, marking a step in the causal pathway
between the tax and reduced SSB consumption.
PMID- 26444623
TI - A closer look at the 21(st) Century Cures Act.
PMID- 26444624
TI - A dormant danger: New therapies target a ubiquitous pathogen known as
cytomegalovirus.
PMID- 26444625
TI - MERS vaccines advance, but will humans or camels get the jab?
PMID- 26444626
TI - Chikungunya is moving fast, but so are researchers in the field.
PMID- 26444627
TI - Bugging out over Chagas: Bioluminescent protozoans and old drugs might help
unravel kissing-bug disease.
PMID- 26444628
TI - The Canadian MD/PhD training program needs reinstated support.
PMID- 26444630
TI - Characterization of extracellular DDX4- or Ddx4-positive ovarian cells.
PMID- 26444631
TI - Adult human and mouse ovaries lack DDX4-expressing functional oogonial stem
cells.
PMID- 26444632
TI - Woods and Tilly reply.
PMID- 26444633
TI - CD47 blockade as another immune checkpoint therapy for cancer.
PMID- 26444634
TI - Antigen-presenting cells look within during influenza infection.
PMID- 26444635
TI - Remodeling the susceptibility to stress-induced depression.
PMID- 26444636
TI - A detour in the quest for oogonial stem cells: methods matter.
PMID- 26444638
TI - Radiation-assisted magnetotransport in two-dimensional electron gas systems:
appearance of zero resistance states.
AB - Zero-resistance states (ZRS) are normally associated with superconducting and
quantum Hall phases. Experimental detection of ZRS in two-dimensional electron
gas (2DEG) systems irridiated by microwave(MW) radiation in a magnetic field has
been quite a surprise. We develop a semiclassical transport formalism to explain
the phenomena. We find a sequence of Zero-Resistance States (ZRS) inherited from
the suppression of Shubnikov-de Haas (SdH) oscillations under the influence of
high-frequency and large amplitude microwave radiation. Furthermore, the ZRS are
well pronounced and persist up to broad intervals of magnetic field as observed
in experiments on microwave illuminated 2DEG systems.
PMID- 26444637
TI - Natural and therapy-induced immunosurveillance in breast cancer.
AB - The immunosurveillance theory postulates that tumors evolve and progress in an
uncontrolled fashion only when anticancer immune responses fail. Natural
immunosurveillance clearly influences human breast cancer (BC) progression
because the prognosis of BC patients is dictated by the density, composition and
activity of the tumor immune infiltrate at diagnosis. Moreover, chemotherapeutic
and radiotherapeutic regimens commonly employed for the treatment of BC affect
the tumor immune infiltrate, and accumulating data suggest that the clinical
efficacy of these treatments is largely determined by T cell-dependent tumor
specific immune responses. In addition, the mechanism of action of targeted
anticancer therapeutics, such as the erb-b2 receptor tyrosine kinase 2 (ERBB2)
targeting agent trastuzumab, involves the innate and adaptive arms of the immune
system. In this Review, we discuss these findings as well as preliminary evidence
indicating that immunotherapy constitutes a promising option for the treatment of
BC. Moreover, we point out that the successful implementation of immunotherapy to
BC management requires the optimization of current immunotherapeutic regimens and
the identification of immunological biomarkers that enable improved risk
stratification and the design of personalized, dynamic treatment plans.
PMID- 26444639
TI - Depressive symptoms influence use of feedback for motor learning and recovery in
chronic stroke.
AB - PURPOSE: Sensorimotor impairments and depressive symptoms (PSD) influence arm
motor recovery post-stroke. Feedback provision improves upper limb motor learning
in patients with chronic stroke but factors including PSD may affect ability to
use feedback. We evaluated the influence of PSD on the ability to use auditory
feedback for upper limb recovery and motor learning in patients with chronic
stroke. METHODS: Participants (n = 24) practiced 72 pointing movements/session (6
targets, 12 sessions, randomized) with auditory feedback on movement speed and
trunk displacement. The presence of PSD (Beck's Depression Inventory; BDI-II) was
assessed at pre-intervention (PRE). Arm motor impairment (Fugl-Meyer Assessment,
shoulder horizontal adduction, shoulder flexion, elbow extension ranges, trunk
displacement) and arm use (Motor Activity Log) were assessed at PRE, immediately
after (POST) and retention (3 mos; RET). Participants were divided into two
groups based on BDI-II scores: >= 14/63 (DEP group; n = 8; score: 20.5 +/- 7.5)
and <= 13/63 (no PSD (ND) group; n = 16; score: 5.0 +/- 3.8). Changes in
impairment and arm use levels were assessed (mixed-model ANOVAs). RESULTS: All
participants improved arm use. DEP had lower Fugl-Meyer scores, used more
compensatory trunk displacement and had lower shoulder horizontal adduction range
compared to ND. CONCLUSION: The presence of PSD diminished the ability to use
auditory feedback for arm motor recovery and motor learning.
PMID- 26444640
TI - Neuroprotective effects of Aceglutamide on motor function in a rat model of
cerebral ischemia and reperfusion.
AB - PURPOSE: To investigate the effect and underlying mechanism of Aceglutamide on
motor dysfunction in rats after cerebral ischemia-reperfusion. METHODS: Adult
male Sprague-Dawley rats were subjected to 2 h transient middle cerebral artery
occlusion (MCAO). Aceglutamide or vehicle was intraperitoneally given to rats at
24 h after reperfusion and lasted for 14 days. Subsequently functional recovery
was assessed and number of tyrosine hydroxylase (TH)-positive neurons in
substantia nigra (SN) was analyzed. Tumor necrosis factor receptor-associated
factor 1(TRAF1), P-Akt and Bcl-2/Bax were determined in mesencephalic tissue by
Western blot method. PC12 cells and primary cultured mesencephalic neurons were
employed to further investigate the mechanism of Aceglutamide. RESULTS:
Aceglutamide treatment improved behavioral functions, reduced the infarction
volume, and elevated the number of TH-positive neurons in the SN. Moreover,
Aceglutamide significantly attenuated neuronal apoptosis in the SN. Meanwhile
Aceglutamide treatment significantly inhibited the expression of TRAF1 and up
regulated the expression of P-Akt and Bcl-2/Bax ratio both in vitro and in vivo.
CONCLUSIONS: Aceglutamide ameliorated motor dysfunction and delayed neuronal
death in the SN after ischemia, which involved the inhibition of pro-apoptotic
factor TRAF1 and activation of Akt/Bcl-2 signaling pathway. These data provided
experimental information for applying Aceglutamide to ischemic stroke treatment.
PMID- 26444641
TI - Electrodeposited MnO(x)/PEDOT Composite Thin Films for the Oxygen Reduction
Reaction.
AB - Manganese oxide (MnOx) was anodically coelectrodeposited with poly(3,4
ethylenedioxythiophene) (PEDOT) from an aqueous solution of Mn(OAc)2, 3,4
ethylenedioxythiophene, LiClO4 and sodium dodecyl sulfate to yield a MnOx/PEDOT
composite thin film. The MnOx/PEDOT film showed significant improvement over the
MnOx only and PEDOT only films for the oxygen reduction reaction, with a >0.2 V
decrease in onset and half-wave overpotential and >1.5 times increase in current
density. Furthermore, the MnOx/PEDOT films were competitive with commercial
benchmark 20% Pt/C, outperforming it in the half-wave ORR region and exhibiting
better electrocatalytic selectivity for the oxygen reduction reaction upon
methanol exposure. The high activity of the MnOx/PEDOT composite is attributed to
synergistic charge transfer capabilities, attained by coelectrodepositing MnOx
with a conductive polymer while simultaneously achieving intimate substrate
contact.
PMID- 26444642
TI - Correction: Fine Mapping of Dominant X-Linked Incompatibility Alleles in
Drosophila Hybrids.
PMID- 26444643
TI - On the Construction of Property Based Diabatizations: Diabolical Singular Points.
AB - Diabatizations achieved by diagonalization of a property operator or as the
extremum of a molecular property are numerous and widely used, although for a
particular system a given property method may have limited accuracy or even fail
catastrophically. These failures are usually analyzed in terms of limitations of
the chosen property or method. Here we introduce an alternative perspective,
failure attributable to singularities in the defining equations. The singular
subspace is analogous to the conical intersection seam in potential energy
surfaces. Using the archetypical NH3 nonadiabatic photodissociation, it is shown
that for two states the diabatization condition has singularities on a subspace
of dimension N - 2, where N = 3N(atom) - 6, is the number of internal
coordinates. This singular subspace is distinct from the N - 2-dimensional seam
of conical intersections of the electronic Hamiltonian and results incorrectly,
in singular derivative couplings between diabatic states in unexpected regions of
nuclear coordinate space. Simple indicators are developed that provide ways to
anticipate and avoid these singularities.
PMID- 26444645
TI - The Incidence of Gastric Adenocarcinoma Among Patients With Gastric Intestinal
Metaplasia: A Long-term Cohort Study.
AB - BACKGROUND AND AIMS: Gastric intestinal metaplasia (IM) has been known as a
premalignant condition, but estimates of its cancer risk vary widely. We aimed to
analyze cancer risk of gastric IM by a long-term cohort study. METHODS: We
conducted a hospital-based study that included all patients with gastric IM
between 1992 and 2010, and the development of gastric adenocarcinoma was
evaluated until July 2011. Patients developing gastric cancer <=180 days after
the index diagnosis of IM were excluded. The incidence rate, the cumulative
incidence, and the standardized incidence ratio (SIR) of gastric cancer were
determined, and hazard ratios (HRs) of risk factors were calculated. RESULTS: We
identified 7059 patients with a median follow-up duration of 5.1 years, and 81
patients developed gastric adenocarcinoma during the study period. The 5-, 10-,
and 15-year cumulative incidences of gastric cancer were 0.9% [95% confidence
interval (CI), 0.6-1.1), 2.0% (95% CI, 1.5-2.6), and 3.0% (95% CI, 2.0-4.0),
respectively. On multivariate analysis, older age (eg, 75 y and above; HR=7.4;
95% CI, 2.8-19.6), low-grade dysplasia (HR=4.0; 95% CI, 2.1-7.9), and high-grade
dysplasia (HR=18.8; 95% CI, 9.0-39.5) were independent risk factors. As compared
with the risk in the general population, the SIR of gastric cancer among patients
with gastric IM was 2.5 (95% CI, 2.0-3.1). However, the SIR was only 2.0 (95% CI,
1.5-2.6) in the nondysplasia subgroup, but was up to 35.2 (95% CI, 15.2-69.4) in
the high-grade dysplasia subgroup. CONCLUSIONS: Gastric IM is an important risk
factor for gastric cancer, but surveillance should be arranged only for those at
an especially high risk.
PMID- 26444644
TI - Label-Free Nanoplasmonic-Based Short Noncoding RNA Sensing at Attomolar
Concentrations Allows for Quantitative and Highly Specific Assay of MicroRNA-10b
in Biological Fluids and Circulating Exosomes.
AB - MicroRNAs are short noncoding RNAs consisting of 18-25 nucleotides that target
specific mRNA moieties for translational repression or degradation, thereby
modulating numerous biological processes. Although microRNAs have the ability to
behave like oncogenes or tumor suppressors in a cell-autonomous manner, their
exact roles following release into the circulation are only now being unraveled
and it is important to establish sensitive assays to measure their levels in
different compartments in the circulation. Here, an ultrasensitive localized
surface plasmon resonance (LSPR)-based microRNA sensor with single nucleotide
specificity was developed using chemically synthesized gold nanoprisms attached
onto a solid substrate with unprecedented long-term stability and reversibility.
The sensor was used to specifically detect microRNA-10b at the attomolar (10(-18)
M) concentration in pancreatic cancer cell lines, derived tissue culture media,
human plasma, and media and plasma exosomes. In addition, for the first time, our
label-free and nondestructive sensing technique was used to quantify microRNA-10b
in highly purified exosomes isolated from patients with pancreatic cancer or
chronic pancreatitis, and from normal controls. We show that microRNA-10b levels
were significantly higher in plasma-derived exosomes from pancreatic ductal
adenocarcinoma patients when compared with patients with chronic pancreatitis or
normal controls. Our findings suggest that this unique technique can be used to
design novel diagnostic strategies for pancreatic and other cancers based on the
direct quantitative measurement of plasma and exosome microRNAs, and can be
readily extended to other diseases with identifiable microRNA signatures.
PMID- 26444646
TI - Obesity and Cardiovascular Risk in Adults With Celiac Disease.
AB - BACKGROUND: Patients with celiac disease (CD) may be at an increased risk of
cardiovascular disease (CVD), yet CVD risk factors are not well defined in CD.
The validated Framingham Heart Study 10-year general CVD risk score (FRS) that
incorporates traditional CVD risk factors including body mass index (BMI) has not
been previously studied in CD patients. AIMS: To compare BMI and FRS in CD
patients with population-based controls. METHODS: Biopsy-proven CD patients were
ascertained retrospectively and data on BMI, systolic blood pressure,
hypertension, smoking status, and diabetes were obtained at initial and follow-up
visits. FRS was calculated and compared with 4 matched general population non-CD
controls from the 2009 to 2010 National Health and Nutrition Examination Survey
(NHANES). RESULTS: Of 258 total CD patients, 38.3% were overweight or obese
compared with 69.8% of controls (P<0.001). In total, 174 CD patients met the
inclusion criteria for FRS calculation. Of these, the median FRS was lower in CD
patients compared with controls (3.9 vs. 4.2; P=0.011). In CD patients, tobacco
use was significantly lower (P<0.001), whereas systolic blood pressure was
significantly higher (P<0.01) than controls. CONCLUSIONS: Global CVD risk is
lower among patients with CD compared with population controls. Lower BMI and
tobacco use among CD patients could account for this difference. These results
suggest that factors other than those measured by FRS could contribute to the
increased risk of CVD in CD observed in some studies.
PMID- 26444647
TI - Identifying Minimal Changes in Nonerosive Reflux Disease: Is the Pay Worth the
Labor?
AB - Gastroesophageal reflux disease has a variable presentation on upper endoscopy.
Gastroesophageal reflux disease can be divided into 3 endoscopic categories:
Barrett's esophagus, erosive esophagitis, and normal mucosa/nonerosive reflux
disease (NERD). Each of these phenotypes behave in a distinct manner, in regards
to symptom response to treatment, and risk of development of complications such
as esophageal adenocarcinoma. Recently, it has been proposed to further
differentiate NERD into 2 categories: those with and those without "minimal
changes." These minimal changes include endoscopic abnormalities, such as villous
mucosal surface, mucosal islands, microerosions, and increased vascularity at the
squamocolumnar junction. Although some studies have shown that patients with
minimal changes may have higher rates of esophageal acid exposure compared with
those without minimal changes, it is currently unclear if these patients behave
differently than those currently categorized as having NERD. The clinical utility
of identifying these lesions should be weighed against the cost of the requisite
equipment and the additional time required for diagnosis, compared with
conventional white light endoscopy.
PMID- 26444648
TI - Quality and Safety in Health Care, Part IV: Quality and Cancer Care.
AB - The 1999 Institute of Medicine report Ensuring Quality Cancer Care discussed the
difference between the actual cancer care received in the United States and the
care that the patients should get, as well as some points to consider in
delivering optimum care. In 2012, a follow-up review article in the journal
Cancer entitled "Ensuring quality cancer care" indicated that there had been some
interval progress, but more are needed to be done. The 2013 Institute of Medicine
report Delivering High-Quality Cancer Care: Charting a New Course for a System in
Crisis indicated that there are continuing major problems with cancer care and
that they advocated a national system of quality reporting and a major
information technology system to capture and help assess the data.
PMID- 26444649
TI - Visualization of Lymph Nodal and Hepatic Metastases of Medullary Thyroid
Carcinoma on 18F-Fluoride PET/CT.
AB - F-fluoride uptake in soft tissue metastases has been previously described.
Herein, we report a case of F-fluoride uptake in lymph nodal and hepatic
metastases of medullary thyroid carcinoma. Simultaneous CT showed calcified
lesions in these regions.
PMID- 26444650
TI - 18F-NaF PET/CT Findings in Fibrous Dysplasia.
AB - A 43-year-old woman with breast cancer underwent Tc-hydroxymethylene
diphosphonate bone scintigraphy for preoperative workup. An abnormal lesion with
increased uptake was found in the right humeral shaft, and F-NaF bone PET/CT was
performed for clarification. There was high uptake of F-NaF without cortical bone
disruption in the right humeral shaft, corresponding to the site on bone
scintigraphy. Upper arm MRI was performed subsequently, and metastasis was
suggested as a differential diagnosis. However, this lesion was pathologically
diagnosed as fibrous dysplasia after curettage surgery.
PMID- 26444651
TI - Pulmonary Artery Sarcoma Detected on 18F-FDG PET/CT With Unusual Findings.
AB - A 32-year-old woman, who presented with "sharp pain" in the right chest for more
than 1 month and worsening dyspnea and fever for 10 days, was initially thought
to have a pulmonary embolism. Cardiac ultrasound showed an ill-defined echogenic
mass within the pulmonary trunk. F-FDG PET/CT was performed for further
evaluation. PET/CT showed an intense hypermetabolism in the main, bilateral
proximal, and the right main pulmonary arteries, suggesting the presence of a
malignant lesion. Biopsy confirmed the lesion as a primary pulmonary artery
sarcoma.
PMID- 26444652
TI - Light-Driven Heterogeneous Reduction of Carbon Dioxide: Photocatalysts and
Photoelectrodes.
PMID- 26444653
TI - Freezing-Enhanced Dissolution of Iron Oxides: Effects of Inorganic Acid Anions.
AB - Dissolution of iron from mineral dust particles greatly depends upon the type and
amount of copresent inorganic anions. In this study, we investigated the roles of
sulfate, chloride, nitrate, and perchlorate on the dissolution of maghemite and
lepidocrocite in ice under both dark and UV irradiation and compared the results
with those of their aqueous counterparts. After 96 h of reaction, the total
dissolved iron in ice (pH 3 before freezing) was higher than that in the aqueous
phase (pH 3) by 6-28 times and 10-20 times under dark and UV irradiation,
respectively. Sulfuric acid was the most efficient in producing labile iron under
dark condition, whereas hydrochloric acid induced the most dissolution of the
total and ferrous iron in the presence of light. This ice-induced dissolution
result was also confirmed with Arizona Test Dust (AZTD). In the freeze-thaw
cycling test, the iron oxide samples containing chloride, nitrate, or perchlorate
showed a similar extent of total dissolved iron after each cycling while the
sulfate-containing sample rapidly lost its dissolution activity with repeating
the cycle. This unique phenomenon observed in ice might be related to the freeze
concentration of protons, iron oxides, and inorganic anions in the liquid-like
ice grain boundary region. These results suggest that the ice-enhanced
dissolution of iron oxides can be a potential source of bioavailable iron, and
the acid anions critically influence this process.
PMID- 26444654
TI - The drawing effect: Evidence for reliable and robust memory benefits in free
recall.
AB - In 7 free-recall experiments, the benefit of creating drawings of to-be
remembered information relative to writing was examined as a mnemonic strategy.
In Experiments 1 and 2, participants were presented with a list of words and were
asked to either draw or write out each. Drawn words were better recalled than
written. Experiments 3-5 showed that the memory boost provided by drawing could
not be explained by elaborative encoding (deep level of processing, LoP), visual
imagery, or picture superiority, respectively. In Experiment 6, we explored
potential limitations of the drawing effect, by reducing encoding time and
increasing list length. Drawing, relative to writing, still benefited memory
despite these constraints. In Experiment 7, the drawing effect was significant
even when encoding trial types were compared in pure lists between participants,
inconsistent with a distinctiveness account. Together these experiments indicate
that drawing enhances memory relative to writing, across settings, instructions,
and alternate encoding strategies, both within- and between-participants, and
that a deep LoP, visual imagery, or picture superiority, alone or collectively,
are not sufficient to explain the observed effect. We propose that drawing
improves memory by encouraging a seamless integration of semantic, visual, and
motor aspects of a memory trace.
PMID- 26444655
TI - T-Cell Cytokines as Predictive Markers of the Risk of Allograft Rejection.
AB - Over the last decade, several biomarkers and surrogate markers have surfaced as
promising predictive markers of risk of rejection in solid organ transplantation.
The monitoring of these markers can help to improve graft and recipient care by
personalizing immunomodulatory therapies. The complex immune system response
against an implanted graft can change during long-term follow-up, and the dynamic
balance between effector and regulatory T-cell populations is a crucial factor in
antidonor response, risk of rejection, and immunosuppression requirements.
Therefore, at any time before and after transplantation, T-effector activity,
which is associated with increased production and release of proinflammatory
cytokines, can be a surrogate marker of the risk of rejection and need for
immunosuppression. In addition, immunosuppressive drugs may have a different
effect in each individual patient. The pharmacokinetics and pharmacodynamics of
these drugs show high interpatient variability, and pharmacodynamic markers,
strongly associated with the specific mechanism of action, can potentially be
used to measure individual susceptibility to a specific immunosuppressive agent.
The monitoring of a panel of valid biomarkers can improve patient stratification
and the selection of immunosuppressive drugs. After transplantation, therapy can
be adjusted based on the prediction of rejection episodes (maintained
alloreactivity), the prognosis of allograft damage, and the individual's response
to the drugs. This review will focus on current data indicating that changes in
the T-cell production of the intracellular cytokines interferon-gamma and
interleukin-2 could be used to predict the risk of rejection and to guide
immunosuppressive therapy in transplant recipients.
PMID- 26444656
TI - Intimate relationships in young adults with perinatally acquired HIV: a
qualitative study of strategies used to manage HIV disclosure.
AB - An increasing number of children born with perinatally acquired HIV (PAH) are
surviving into late adolescence and early adulthood. At this developmental stage,
forming and sustaining intimate relationships is important. Young adults with PAH
face both normative challenges and additional, HIV-related, relationship
stressors. One key issue is the decision about whether and how to share their HIV
status with others. Being able to disclose one's HIV status to sexual partners
may reduce the risk of onward HIV transmission but is associated with the fear of
rejection. There has been little research on how young people with PAH manage
such disclosure-related stressors in intimate relationships. This study examined
how disclosure challenges are managed by young adults with PAH in the UK within
their intimate relationships. Seven participants (five females and two males)
currently or previously in an intimate relationship, aged 18-23 years, were
recruited from a UK hospital clinic. The majority of participants were of sub
Saharan African origins. They took part in in-depth interviews, with data
analysed according to the principles of interpretative phenomenological analysis.
Four themes were elicited: (1) decisions about starting, continuing or resuming
relationships shaped by disclosure, (2) disclosing early to avoid the pain of
future rejection, (3) using condoms to avoid disclosure and (4) testing likely
partner reactions to disclosure. The study revealed the significant extent to
which HIV disclosure affected the experience of relationships in this population.
Interventions to support adolescents and young adults with PAH to disclose to
their partners should be developed alongside guidance for professionals. Future
research should include older samples of adults with PAH and studies in sub
Saharan African settings.
PMID- 26444657
TI - Editor's Commentary.
PMID- 26444658
TI - Biological versus Mechanical Heart Valve Prostheses. Has the Paradigm Shifted
Definitively?
PMID- 26444659
TI - Trends in Surgical Aortic Valve Replacement in More Than 3,000 Consecutive Cases
in the Era of Transcatheter Aortic Valve Implantations.
AB - Objectives Biological prostheses for surgical aortic valve replacement (sAVR) are
increasingly being considered in patients < 60 years of age. Likely, preserving
the option of performing a transcatheter valve-in-valve (ViV) procedure in cases
of structural valve deterioration has contributed to this development. We
assessed the use pattern in sAVR over an 11-year period. Methods From 2002
through 2012, a total of 3,172 patients underwent sAVR at our center. Results
Mean age was 70.4 +/- 10.6 years and mortality was 1.9%. From 2002 to 2012, mean
manufacturer given valve size increased from 22.8 +/- 1.7 to 23.9 +/- 2.0 mm (p <
0.001). Mean true internal diameter and effective orifice area increased from
19.6 to 20.3 mm (p = 0.027) and 1.41 to 1.56 cm(2) (p < 0.001), respectively. Use
of mechanical valves decreased from 10.9 to 1.8% (p < 0.001), and patients were
younger in 2012 than in 2002 (52.8 +/- 16.5 vs. 41.0 +/- 14.3 years; p = 0.028).
Conclusion Profound change of use pattern in sAVR was observed as indication for
biological prostheses became more liberal. Larger prostheses were implanted
during the observational period. Especially in younger patients, optimal sizing
is essential to preserve the option for subsequent ViV procedures.
PMID- 26444660
TI - Authors' Reply.
PMID- 26444661
TI - Anterior Temporal Sulcus: A Reliable Intraoperative Landmark for Accurately
Delineating the Superior Limit of Amygdala Resection during Anterior Temporal
Lobectomy.
AB - BACKGROUND: Reliable anatomical landmarks are essential to avoiding injuries to
the optic tract, anterior choroidal artery and basal ganglia during anterior
temporal lobectomy (ATL). We describe an anatomic landmark, specifically the
anterior temporal sulcus (ATS), as a reliable method to define the anterior
portion of the endorhinal sulcus and the superior limit of amygdala resection.
METHODS: A total of 25 consecutive patients undergoing ATL at Rush University
Medical Center (RUMC) were identified, and their preoperative brain magnetic
resonance imaging (MRI) studies were analyzed. RESULTS: All patients underwent
successful ATL without any complication. There was no injury to the optic tract,
anterior choroidal artery or basal ganglia using ATS as the landmark for the
superior limit of amygdala resection. The ATS was clearly identifiable on coronal
preoperative MRI in 48 out of 50 temporal lobes (96%). The ATS was present in all
25 left temporal lobes (100%); 2 of the 25 right temporal lobes had absent ATS
(8%). Following the ATS posteriorly on coronal MRI, it led to the endorhinal
sulcus and accurately predicted the superior extent of amygdala resection in all
25 patients (48 temporal lobes). CONCLUSION: The ATS is a reliable anatomical
landmark that accurately delineates the superior border of the amygdala during
ATL.
PMID- 26444662
TI - Diagnostic Performance of Transluminal Attenuation Gradient and Noninvasive
Fractional Flow Reserve Derived from 320-Detector Row CT Angiography to Diagnose
Hemodynamically Significant Coronary Stenosis: An NXT Substudy.
AB - PURPOSE: To compare the diagnostic performance of 320-detector row computed
tomography (CT) coronary angiography-derived computed fractional flow reserve
(FFR; FFRCT), transluminal attenuation gradient (TAG; TAG320), and CT coronary
angiography alone to diagnose hemodynamically significant stenosis as determined
by invasive FFR. MATERIALS AND METHODS: This substudy of the prospective NXT
study (no. NCT01757678) was approved by each participating institution's review
board, and informed consent was obtained from all participants. Fifty-one
consecutive patients who underwent 320-detector row CT coronary angiographic
examination and invasive coronary angiography with FFR measurement were included.
Independent core laboratories determined coronary artery disease severity by
using CT coronary angiography, TAG320, FFRCT, and FFR. TAG320 is defined as the
linear regression coefficient between luminal attenuation and axial distance from
the coronary ostium. FFRCT was computed from CT coronary angiography data by
using computational fluid dynamics technology. Diagnostic performance was
evaluated and compared on a per-vessel basis by the area under the receiver
operating characteristic (ROC) curve (AUC). RESULTS: Among 82 vessels, 24 lesions
(29%) had ischemia by FFR (FFR <= 0.80). FFRCT exhibited a stronger correlation
with invasive FFR compared with TAG320 (Spearman rho, 0.78 vs 0.47,
respectively). Overall per-vessel accuracy, sensitivity, specificity, and
positive and negative predictive values for TAG320 (<15.37) were 78%, 58%, 86%,
64%, and 83%, respectively; and those of FFRCT were 83%, 92%, 79%, 65%, and 96%,
respectively. ROC curve analysis showed a significantly larger AUC for FFRCT
(0.93) compared with that for TAG320 (0.72; P = .003) and CT coronary angiography
alone (0.68; P = .008). CONCLUSION: FFRCT computed from 320-detector row CT
coronary angiography provides better diagnostic performance for the diagnosis of
hemodynamically significant coronary stenoses compared with CT coronary
angiography and TAG320.
PMID- 26444663
TI - Quantitative Assessment of Foot Blood Flow by Using Dynamic Volume Perfusion CT
Technique: A Feasibility Study.
AB - PURPOSE: To demonstrate the feasibility of foot blood flow measurement by using
dynamic volume perfusion computed tomographic (CT) technique with the upslope
method in an animal experiment and a human study. MATERIALS AND METHODS: The
human study was approved by the institutional review board, and written informed
consent was obtained from all patients. The animal study was approved by the
research animal care and use committee. A perfusion CT experiment was first
performed by using rabbits. A color-coded perfusion map was reconstructed by
using in-house perfusion analysis software based on the upslope method, and the
measured blood flow on the map was compared with the reference standard
microsphere method by using correlation analysis. A total of 17 perfusion CT
sessions were then performed (a) once in five human patients and (b) twice
(before and after endovascular revascularization) in six human patients.
Perfusion maps of blood flow were reconstructed and analyzed. The Wilcoxon signed
rank test was used to prove significant differences in blood flow before and
after treatment. RESULTS: The animal experiment demonstrated a strong correlation
(R(2) = 0.965) in blood flow between perfusion CT and the microsphere method.
Perfusion maps were obtained successfully in 16 human clinical sessions (94%)
with the use of 32 mL of contrast medium and an effective radiation dose of 0.31
mSv (k factor for the ankle, 0.0002). The plantar dermis showed the highest blood
flow among all anatomic structures of the foot, including muscle, subcutaneous
tissue, tendon, and bone. After a successful revascularization procedure, the
blood flow of the plantar dermis increased by 153% (P = .031). The
interpretations of the color-coded perfusion map correlated well with the
clinical and angiographic findings. CONCLUSION: Perfusion CT could be used to
measure foot blood flow in both animals and humans. It can be a useful modality
for the diagnosis of peripheral arterial disease by providing quantitative
information on foot perfusion status.
PMID- 26444664
TI - Heart Disease and Colon Cancer Prevention Beliefs and Their Association With
Information Seeking and Scanning.
AB - Despite their understanding of the links between (a) information seeking and
scanning and (b) health outcomes, researchers still know relatively little about
the impact of information behaviors on people's disease-related beliefs and
attitudes. The goal of this study was to validate findings linking information
and health behaviors and to assess whether information seeking and scanning are
associated with beliefs about the effectiveness of heart disease and colon cancer
risk prevention behaviors (in regard to exercise, controlling one's diet to
prevent overweight/obesity, and daily fruit and vegetable intake), as well as
determine whether the effects of seeking versus scanning on these beliefs differ.
Data from the Annenberg National Health Communication Survey were analyzed (N =
3,212). For colon cancer, significant main effects were detected for information
scanning for each of the 3 beliefs assessed (p < .05). For heart disease, both
information scanning and heart disease media exposure (p < .05) were associated
with stronger beliefs. Information seeking was not associated with beliefs for
either disease (p > .05). Our results suggest that disease-related cognitions and
beliefs, which ultimately impact decisions to engage in prevention behaviors, may
be influenced most by less purposeful forms of information acquisition.
PMID- 26444666
TI - Congenital esophageal stenosis diagnosed in an infant at 9 month of age.
AB - Esophageal stenosis is a relatively uncommon condition in pediatrics and requires
an accurate diagnostic approach. Here we report the case of a 9-month old female
infant who presented intermittent vomiting, dysphagia and refusal of solid foods
starting after weaning. She was treated for gastroesophageal reflux. At first,
radiological investigation suggested achalasia, while esophagoscopy revelaed a
severe congenital esophageal stenosis at the distal third of the esophagus. She
underwent four endoscopic balloon dilatations that then allowed her to swallow
solid food with intermittent mild dysphagia. After 17 months of esomeprazole
treatment off therapy impedance-pH monitoring was normal. At 29 months of follow
up the child is asymptomatic and eats without problems.Infants with dysphagia and
refusal of solid foods may have undiagnosed medical conditions that need
treatment. Many disorders can cause esophageal luminal stricture; in the
pediatric age the most common are peptic or congenital. Careful assessment with
endoscopy is needed to diagnose these conditions early and referral to a
pediatric gastroenterologic unit may be necessary.
PMID- 26444665
TI - Global analysis of uncapped mRNA changes under drought stress and microRNA
dependent endonucleolytic cleavages in foxtail millet.
AB - BACKGROUND: mRNA degradation plays an important role in the determination of mRNA
abundance and can quickly regulate gene expression. The production of uncapped
mRNAs, an important mechanism of mRNA degradation, can be initiated by decapping
enzymes, endonucleases or small RNAs such as microRNAs (miRNAs). Little is known,
however, about the role of uncapped mRNAs in plants under environmental stress.
RESULTS: Using a novel approach called parallel analysis of RNA ends (PARE), we
performed a global study of uncapped mRNAs under drought stress in foxtail millet
(Setaria italica [L.] P. Beauv.). When both gene degradation (PARE) and gene
transcription (RNA-sequencing) data were considered, four types of mRNA decay
patterns were identified under drought stress. In addition, 385 miRNA-target
interactions were identified in the PARE data using PAREsnip. The PARE analysis
also suggested that two miRNA hairpin processing mechanisms--loop-last and loop
first processing--operate in foxtail millet, with both miR319 and miR156 gene
families undergoing precise processing via the unusual loop-first mechanism.
Finally, we found 11 C4 photosynthesis-related enzymes encoded by drought
responsive genes. CONCLUSIONS: We performed a global analysis of mRNA degradation
under drought stress and uncovered diverse drought-response mechanisms in foxtail
millet. This information will deepen our understanding of mRNA expression under
stressful environmental conditions in gramineous plants. In addition, PARE
analysis identified many miRNA targets and revealed miRNA-precursor processing
modes in foxtail millet.
PMID- 26444667
TI - Negative impact of low body mass index on liver cirrhosis patients with
hepatocellular carcinoma.
AB - BACKGROUND: The impact of obesity on the prognosis of hepatocellular carcinoma
(HCC) has not been well characterized in a Chinese population. Therefore, the aim
of this study was to examine the influence of BMI on the clinicopathological
characteristics and mortality of patients with HCC. METHODS: The study cohort
consisted of 379 patients who were diagnosed with HCC at the First Affiliated
Hospital of Harbin Medical University between June 2012 and August 2014. Study
subjects were divided into two body mass index (BMI) categories: normal weight
(BMI <23 kg/m(2)) and overweight (BMI >=23 kg/m(2)). RESULTS: Of the 379
patients, 44 (11.6%) were underweight (<18.5 kg/m(2)), 172 (45.4%) had a normal
weight (18.5 <= BMI < 23.0), 133 (35.1 %) were overweight (23.0 <= BMI < 27.5),
and 30 (7.9%) were obese (BMI >=27.5). After a median follow-up time of 296
(range, 15-720) days, 168 (44.3%) patients died with median survival time of 159
(range, 15-690) days. Patients with lower BMIs also exhibited a higher liver
related mortality rate (60.6 vs. 22.7%; p = 1.8 * 10(-13)) and a shorter survival
time (353 days vs. 571 days; p = 6.2 * 10(-6)) than patients with higher BMIs. In
multivariate analysis, the BMI class was also found to be a significant
independent impact factor for overall survival (p = 2.2 * 10(-8)), age, alpha
fetoprotein level, Child-Pugh score, treatment strategy, antiviral treatment,
extrahepatic metastasis, and tumor infiltration of the portal vein. CONCLUSIONS:
Our data suggest that lower BMI has a significant impact regarding poor outcomes
in patients with HCC. To better understand the impact of BMI on the prognosis of
HCC patients, more large-scale cohort studies will be necessary.
PMID- 26444668
TI - Combined clinical and genomic signatures for the prognosis of early stage non
small cell lung cancer based on gene copy number alterations.
AB - BACKGROUND: The development of a more refined prognostic methodology for early
non-small cell lung cancer (NSCLC) is an unmet clinical need. An accurate
prognostic tool might help to select patients at early stages for adjuvant
therapies. RESULTS: A new integrated bioinformatics searching strategy, that
combines gene copy number alterations and expression, together with clinical
parameters was applied to derive two prognostic genomic signatures. The proposed
methodology combines data from patients with and without clinical data with a
priori information on the ability of a gene to be a prognostic marker. Two
initial candidate sets of 513 and 150 genes for lung adenocarcinoma (ADC) and
squamous cell carcinoma (SCC), respectively, were generated by identifying genes
which have both: a) significant correlation between copy number and gene
expression, and b) significant prognostic value at the gene expression level in
external databases. From these candidates, two panels of 7 (ADC) and 5 (SCC)
genes were further identified via semi-supervised learning. These panels,
together with clinical data (stage, age and sex), were used to construct the ADC
and SCC hazard scores combining clinical and genomic data. The signatures were
validated in two independent datasets (n = 73 for ADC, n = 97 for SCC),
confirming that the prognostic value of both clinical-genomic models is robust,
statistically significant (P = 0.008 for ADC and P = 0.019 for SCC) and
outperforms both the clinical models (P = 0.060 for ADC and P = 0.121 for SCC)
and the genomic models applied separately (P = 0.350 for ADC and P = 0.269 for
SCC). CONCLUSION: The present work provides a methodology to generate a robust
signature using copy number data that can be potentially used to any cancer.
Using it, we found new prognostic scores based on tumor DNA that, jointly with
clinical information, are able to predict overall survival (OS) in patients with
early-stage ADC and SCC.
PMID- 26444669
TI - When flexibility is not necessarily a virtue: a review of hypermobility syndromes
and chronic or recurrent musculoskeletal pain in children.
AB - Chronic or recurrent musculoskeletal pain is a common complaint in children.
Among the most common causes for this problem are different conditions associated
with hypermobility. Pediatricians and allied professionals should be well aware
of the characteristics of the different syndromes associated with hypermobility
and facilitate early recognition and appropriate management. In this review we
provide information on Benign Joint Hypermobility Syndrome, Ehlers-Danlos
Syndrome, Marfan Syndrome, Loeys-Dietz syndrome and Stickler syndrome, and
discuss their characteristics and clinical management.
PMID- 26444670
TI - Incidence, causes and phenotypes of acute seizures in Kenyan children post the
malaria-decline period.
AB - BACKGROUND: Acute seizures are a common cause of paediatric admissions to
hospitals in Africa, and malaria is an important cause of seizures in endemic
areas. Malaria has declined in the past decade whilst neonatal admissions have
increased, both which may affect the incidence and phenotypes of acute seizures
in African children. METHODS: We examined the effect of recent decline in malaria
and the increasing burden of neonatal admissions on the incidence, causes and
phenotypes of acute seizures admitted to hospital from 2009-2013. We used
logistic regression to measure associations and Poisson regression to calculate
the incidence and rate ratios. RESULTS: The overall incidence of acute seizures
over the 5-year period was 312 per 100,000/year (95% CI, 295-329): 116 per
100,000/year (95% CI, 106-127) for complex seizures and 443 per 100,000 live
births (95% CI, 383-512) for neonatal seizures. Over the period, there was an
increase in incidence of seizures-attributable to malaria (SAM) (incidence rate
ratio (IRR) = 1.25; p < 0.001), but neither non-SAM (IRR = 1.03; p = 0.569) nor
neonatal seizures (IRR = 0.99; p = 0.905). Important causes of acute seizures
were malaria (33%) and respiratory tract infections (19%); and for neonatal
seizures were neonatal sepsis (51%), hypoglycemia (41%) and hypoxic-ischemic
encephalopathy (21%). Mortality occurred in 6% of all acute seizures, being more
common in complex seizures (8%) and neonatal seizures (10 %) than other seizures
(p < 0.001 for both comparisons). CONCLUSIONS: Acute seizures remain common in
children despite a decline in the incidence of malaria; suggesting that causes
for these seizures need to be prevented in the community.
PMID- 26444671
TI - Early treatment with hydroxychloroquine prevents the development of endothelial
dysfunction in a murine model of systemic lupus erythematosus.
AB - INTRODUCTION: Accelerated atherosclerosis is one of the major causes of morbidity
in patients with systemic lupus erythematosus (SLE). Endothelial dysfunction (ED)
is considered an early marker of atherosclerosis. It is a reversible alteration,
thus representing an attractive target for prevention strategies against
cardiovascular disease. Studies have shown that ED occurs in patients with SLE
even in the absence of severe, active disease. Hydroxychloroquine (HCQ) is widely
used in SLE to control disease activity, but its use is also associated with an
improvement in long-term prognosis. Beyond the beneficial effect in well
established disease, our hypothesis is that treatment with HCQ might have a
beneficial impact on ED prevention in SLE. The aim of this study was to assess
the impact of early treatment with HCQ on ED in a murine model of SLE. METHODS:
Twelve-week-old NZB/W F1 (NZ) and C57BL/6 J mice (controls) were allocated to
receive HCQ or vehicle for 6, 12, or 18 weeks. Proteinuria and anti-double
stranded DNA autoantibodies were determined. ED was assessed in mesenteric
arteries (pressurized myography). Nitric oxide (NO) availability and reactive
oxygen species (ROS) production were evaluated. Vascular ROS production was
measured with dihydroethidium (DHE) fluorescent dye. RESULTS: Starting from 18
weeks of age, NZ mice showed a progressive reduction in NO availability, which
was normalized by ascorbic acid and apocynin in the up to 24-week-old group, and
partly ameliorated in older animals. HCQ administration normalized the NO
availability in the up to 24-week-old group, with a partial amelioration in the
30-week-old group. DHE analysis revealed a progressive increment of vascular ROS
generation among NZ groups, which was prevented by apocynin. Similarly, in the NZ
HCQ-treated group, vascular ROS production was abrogated. CONCLUSIONS: The ED
that characterizes this mouse model of SLE is caused by the nicotinamide adenine
dinucleotide phosphate oxidase-driven ROS excess. Very early treatment with HCQ
is able to exert vascular protection via an antioxidant effect.
PMID- 26444672
TI - Quantifying the contribution of changes in healthcare expenditures and smoking to
the reversal of the trend in life expectancy in the Netherlands.
AB - BACKGROUND: Since 2001 the Netherlands has shown a sharp upturn in life
expectancy (LE) after a longer period of slower improvement. This study assessed
whether changes in healthcare expenditure (HCE) explain this reversal in trends
in LE. As an alternative explanation, the impact of changes in smoking behavior
was also evaluated. METHODS: To quantify the contribution of changes in HCE to
changes in LE, we estimated a health-production function using a dynamic panel
regression approach with data on 19 OECD countries (1980-2009), accounting for
temporal and spatial correlation. Smoking-attributable mortality was estimated
using the indirect Peto-Lopez method. RESULTS: As compared to 1990-1999, during
2000-2009 LE in the Netherlands increased by 1.8 years in females and by 1.5
years in males. Whereas changes in the impact of smoking between the two periods
made almost no contribution to the acceleration of the increase in LE, changes in
the trend of HCE added 0.9 years to the LE increase between 2000 and 2009. The
exceptional reversal in the trend of LE and HCE was not found among the other
OECD countries. CONCLUSION: This study suggests that changes in Dutch HCE, and
not in smoking, made an important contribution to the reversal of the trend in
LE; these findings support the view that investments in healthcare are
increasingly important for further progress in life expectancy.
PMID- 26444673
TI - Repeat HIV-testing is associated with an increase in behavioral risk among men
who have sex with men: a cohort study.
AB - BACKGROUND: The Center for Disease Control and Prevention recommends that high
risk groups, like sexually active men who have sex with men (MSM), receive HIV
testing and counseling at least annually. The objective of this study was to
investigate the relationship between voluntary repeat HIV testing and sexual risk
behavior in MSM receiving rapid serologic and nucleic acid amplification testing.
METHODS: We performed a cohort study to analyze reported risk behavior among MSM
receiving the "Early Test", a community-based, confidential acute and early HIV
infection screening program in San Diego, California, between April 2008 and July
2014. The study included 8,935 MSM receiving 17,333 "Early Tests". A previously
published risk behavior score for HIV acquisition in MSM (i.e. Menza score) was
chosen as an outcome to assess associations between risk behaviors and number of
repeated tests. RESULTS: At baseline, repeat-testers (n = 3,202) reported more
male partners and more condomless receptive anal intercourse (CRAI) when compared
to single-testers (n = 5,405, all P <0.001). In 2,457 repeat testers there was a
strong association observed between repeated HIV tests obtained and increased
risk behavior, with number of male partners, CRAI with high risk persons, non
injection stimulant drug use, and sexually transmitted infections all increasing
between the first and last test. There was also a linear increase of risk (i.e.
high Menza scores) with number of tests up to the 17th test. In the multivariable
mixed effects model, more HIV tests (OR = 1.18 for each doubling of the number of
tests, P <0.001) and younger age (OR = 0.95 per 5-year increase, P = 0.006) had
significant associations with high Menza scores. CONCLUSIONS: This study found
that the highest risk individuals for acquiring HIV (e.g. candidates for
antiretroviral pre-exposure prophylaxis) can be identified by their testing
patterns. Future studies should delineate causation versus association to improve
prevention messages delivered to repeat testers during HIV testing and counseling
sessions.
PMID- 26444674
TI - Determinants of ventricular arrhythmias in human explanted hearts with dilated
cardiomyopathy.
AB - BACKGROUND: The molecular and cellular determinants of ventricular tachycardia
(VT) in patients with nonischaemic dilated cardiomyopathy (NIDCM) remain poorly
defined. MATERIALS AND METHODS: We examined 20 NIDCM hearts where VT was reported
in 10 cases and VT was absent in 10 cases, using a double-blinded case-control
study design, and assessed the molecular and cellular features of the adverse
myocardial remodelling. RESULTS: Explanted hearts from patients with VT showed
greater hypertrophic changes based on cardiomyocyte cross-sectional area and
expression of disease markers, and increased myocardial fibrosis which extended
into the left ventricular and right ventricular outflow tract regions. The VT
group also showed increased oxidative stress with reduction in reduced
glutathione levels. Connexin 43 levels in the intercalated discs showed increased
levels in the VT group with reduced phosphorylation. Microarray mRNA analysis of
gene expression in the left ventricle (LV) free wall revealed several families of
genes which were differentially upregulated or downregulated in hearts with
documented VT compared to hearts without VT. Notably, we identified reduced
expression of the Ca(2+) -activated K(+) channel (KCNN2) and increased expression
of the transient receptor potential cation channel 7 (TRPM7) and intracellular
chloride channel 3. Western blot analysis on LV membrane fractions showed reduced
KCNN2 and increased TRPM7 levels in hearts with VT. CONCLUSIONS: In explanted
human hearts with NIDCM, VT is associated with greater hypertrophy, oxidative
stress and myocardial fibrosis, differential gene expression, and altered ion
channel levels indicative of a distinctive adverse myocardial remodelling process
associated with clinically significant VT.
PMID- 26444675
TI - Prospective study of the primary evaluation of 1016 horses with clinical signs of
abdominal pain by veterinary practitioners, and the differentiation of critical
and non-critical cases.
AB - BACKGROUND: The majority of research on the evaluation of horses with colic is
focused on referral hospital populations. Early identification of critical cases
is important to optimise outcome and welfare. The aim of this prospective study
was to survey the primary evaluation of horses with clinical signs of abdominal
pain by veterinary practitioners, and compare the initial presentation of
critical and non-critical cases. RESULTS: Data from 1016 primary evaluations of
horses presenting with clinical signs of colic were submitted by 167 veterinary
practitioners across the United Kingdom over a 13 month period. The mean age of
the study population was 13.5 years (median 12.0, range 0-42). Mean heart rate on
primary presentation was 47 beats/min (median 44, range 18-125), mean respiratory
rate was 20 breaths/min (median 16, range 6-100), and median gastrointestinal
auscultation score (0-12, minimum-maximum) was 5 (range 0-12). Clinical signs
assessed using a behavioural severity score (0-17, minimum-maximum), were between
0 and 6 in 70.4 % of cases, and 7-12 for 29.6 % of cases. Rectal examination was
performed in 73.8 % of cases. Cases that responded positively to simple medical
treatment were categorised retrospectively as 'non-critical'; cases that required
intensive medical treatment, surgical intervention, died or were euthanased were
categorised as 'critical'. Eight-hundred-and-twenty-two cases met these criteria;
76.4 % were 'non-critical' and 23.6 % were 'critical'. Multivariable logistic
regression was used to identify features of the clinical presentation associated
with critical cases. Five variables were retained in the final multivariable
model: combined pain score: (OR 1.19, P < 0.001, 95 % CI 1.09-1.30), heart rate
(OR 1.06, P < 0.001, 95 % CI 1.04-1.08), capillary refill time >2.5 s (OR 3.21, P
= 0.046, 95 % CI 1.023-10.09), weak pulse character (OR 2.90, P = 0.004, 95 % CI
1.39-5.99) and absence of gut sounds in >=1 quadrant (OR 3.65, P < 0.001, 95 % CI
2.08-6.41). CONCLUSIONS: This is the first study comparing the primary
presentation of critical and non-critical cases of abdominal pain. Pain, heart
rate, gastrointestinal borborygmi and simple indicators of hypovolaemia were
significant indicators of critical cases, even at the primary veterinary
examination, and should be considered essential components of the initial
assessment and triage of horses presenting with colic.
PMID- 26444676
TI - Brief analysis of causes of sensitive skin and advances in evaluation of anti
allergic activity of cosmetic products.
AB - This review focuses on the causes of sensitive skin and elaborates on the
relationship between skin sensitivity and skin irritations and allergies, which
has puzzled cosmetologists. Here, an overview is presented of the research on
active ingredients in cosmetic products for sensitive skin (anti-sensitive
ingredients), which is followed by a discussion of their experimental efficacy.
Moreover, several evaluation methods for the efficacy of anti-sensitive
ingredients are classified and summarized. Through this review, we aim to provide
the cosmetic industry with a better understanding of sensitive skin, which could
in turn provide some theoretical guidance to the research on targeted cosmetic
products.
PMID- 26444677
TI - Validation of 10-Minute Delayed Hepatocyte Phase Imaging with 30 degrees Flip
Angle in Gadoxetic Acid-Enhanced MRI for the Detection of Liver Metastasis.
AB - OBJECTIVES: To compare 10-minute delayed hepatocyte phase imaging using a 30
degrees flip angle (10 min-FA30) and 20-minute hepatocyte phase imaging using a
10 degrees FA (20 min-FA10) in gadoxetic acid-enhanced MRI of patients with
possible liver metastases, regarding lesion-to-liver contrast-to-noise ratio
(CNR) and focal hepatic lesion (FHL) detection to evaluate whether 10 min-FA30
would be superior to 20 min-FA10. MATERIALS AND METHODS: Eighty-three patients
with 248 liver metastases and 78 benign FHLs who underwent gadoxetic acid
enhanced MRI with 10 min-FA30 and 20 min-FA10 were enrolled. Lesion-to-liver CNRs
were compared between the two image groups. Two radiologists independently
assessed the presence of FHLs using a four-point scale and detection sensitivity
was calculated. RESULTS: The mean CNR for liver metastases on the 10 min-FA30
(248.5 +/- 101.6) were significantly higher than that of the 20 min-FA10 (187.4
+/- 77.4) (p < 0.001). The mean CNR difference between the two image groups was
61.2 +/- 56.8. There was no significant difference in detection sensitivity of
FHLs for two readers between 10 min-FA30 (mean 97.7%) and 20 min-FA10 (mean
97.9%), irrespective of the lesion size or malignancy. CONCLUSION: 10 min-FA30
yielded higher CNR with similar sensitivity compared to 20 min-FA10. This finding
indicates that 10 min-FA30 can potentially replace 20 min-FA10 with higher
diagnostic performance and save 10 minutes of time.
PMID- 26444678
TI - Catalytic enantioselective addition of isocyanoacetate to 3-methyl-4-nitro-5
styrylisoxazoles under phase transfer catalysis conditions.
AB - The reaction between 3-methyl-4-nitro-5-styrylisoxazoles and ethyl
isocyanoacetate proceeded under phase transfer catalysis to give enantioenriched
monoadducts in high enantiomeric excess (up to 99% ee). The resulting adducts
were subsequently cyclised to give 2,3-dihydropyrroles and substituted
pyrrolidines in identical high ees and as a single diastereoisomer.
PMID- 26444679
TI - Ab initio spectroscopic characterization of borane, BH, in its X1Sigma+
electronic state.
AB - The accurate potential energy and electric dipole moment functions of borane, BH,
in its X1Sigma+ electronic state have been determined from ab initio calculations
using the multireference averaged coupled-pair functional method in conjunction
with the correlation-consistent core-valence basis sets up to septuple-zeta
quality. The higher-order electron correlation, scalar relativistic, adiabatic,
and nonadiabatic effects were discussed. Vibration-rotation energy levels of the
(11)BH, (11)BD, (10)BH, and (10)BD isotopologues were predicted to near
"spectroscopic" accuracy. For the main isotopologue (11)BH, the adiabatic
dissociation energy D0 and the effective equilibrium internuclear distance r(e)
were predicted to be 28,469 +/- 10 cm(-1) and 1.23214 +/- 0.0001 A, respectively.
PMID- 26444680
TI - Differential Metabolic Profiles during the Albescent Stages of 'Anji Baicha'
(Camellia sinensis).
AB - 'Anji Baicha' is an albino tea cultivar with white shoots at low air temperature
and green shoots at high air temperature in early spring. The metabolite contents
in the shoots dynamically vary with the color changes and with shoot development.
To investigate the metabolomic variation during the albescent and re-greening
stages, gas chromatography-mass spectrometry combined with multivariate analysis
were applied to analyze the metabolite profiles in the different color stages
during the development of 'Anji Baicha' leaves. The metabolite profiles of three
albescent stages, including the yellow-green stage, the early albescent stage,
and the late albescent stage, as well as the re-greening stage were distinguished
using principal component analysis, revealing that the distinct developmental
stages were likely responsible for the observed metabolic differences.
Furthermore, a group classification and pairwise discrimination was revealed
among the three albescent stages and re-greening stage by partial least squares
discriminant analysis. A total of 65 differential metabolites were identified
with a variable influence on projection greater than 1. The main differential
metabolic pathways of the albescent stages compared with the re-greening stage
included carbon fixation in photosynthetic organisms and the phenylpropanoid and
flavonoid biosynthesis pathways. Compared with the re-greening stage, the
carbohydrate and amino acid metabolic pathways were disturbed during the
albescent stages. During the albescent stages, the sugar (fructofuranose), sugar
derivative (glucose-1-phosphate) and epicatechin concentrations decreased,
whereas the amino acid (mainly glycine, serine, tryptophan, citrulline,
glutamine, proline, and valine) concentrations increased. These results reveal
the changes in metabolic profiling that occur during the color changes associated
with the development of the albino tea plant leaves.
PMID- 26444681
TI - Otx2 Requires Lmx1b to Control the Development of Mesodiencephalic Dopaminergic
Neurons.
AB - Studying the development of mesodiencephalic dopaminergic (mdDA) neurons provides
an important basis for better understanding dopamine-associated brain functions
and disorders and is critical for establishing cell replacement therapy for
Parkinson's disease. The transcription factors Otx2 and Lmx1b play a key role in
the development of mdDA neurons. However, little is known about the genes
downstream of Otx2 and Lmx1b in the pathways controlling the formation of mdDA
neurons in vivo. Here we report on our investigation of Lmx1b as downstream
target of Otx2 in the formation of mdDA neurons. Mouse mutants expressing Otx2
under the control of the En1 promoter (En1+/Otx2) showed increased Otx2
expression in the mid-hindbrain region, resulting in upregulation of Lmx1b and
expansion of mdDA neurons there. In contrast, Lmx1b-/- mice showed decreased
expression of Otx2 and impairments in several aspects of mdDA neuronal formation.
To study the functional interaction between Otx2 and Lmx1b, we generated compound
mutants in which Otx2 expression was restored in mice lacking Lmx1b
(En1+/Otx2;Lmx1b-/-). In these animals Otx2 was not sufficient to rescue any of
the aberrations in the formation of mdDA neurons caused by the loss of Lmx1b, but
rescued the loss of ocular motor neurons. Gene expression studies in Lmx1b-/-
embryos indicated that in these mutants Wnt1, En1 and Fgf8 expression are induced
but subsequently lost in the mdDA precursor domain and the mid-hindbrain
organizer in a specific, spatio-temporal manner. In summary, we demonstrate that
Otx2 critically depends on Lmx1b for the formation of mdDA neurons, but not for
the generation of ocular motor neurons. Moreover, our data suggest that Lmx1b
precisely maintains the expression pattern of Wnt1, Fgf8 and En1, which are
essential for mid-hindbrain organizer function and the formation of mdDA neurons.
PMID- 26444682
TI - Enhanced stem cell-derived cardiomyocyte differentiation in suspension culture by
delivery of nitric oxide using S-nitrosocysteine.
AB - The development of cell-based treatments for heart disease relies on the creation
of functionally mature stem cell-derived cardiomyocytes employing in vitro
culture suspension systems, a process which remains a formidable and expensive
endeavor. The use of nitric oxide as a signaling molecule during differentiation
has demonstrated the potential for creating increased numbers of spontaneously
contracting embryoid bodies in culture; however, the effects of nitric oxide
signaling on the function and maturation of stem cell-derived cardiomyocytes is
not well understood. In this study, the effects of nitric oxide on mouse
embryonic stem cell-derived cardiomyocyte contractile activity, protein, and gene
expression, and calcium handling were quantified. Embryoid bodies (EBs) formed
using the hanging drop method, were treated with the soluble nitric oxide donor S
nitrosocysteine (CysNO) over a period of 18 days in suspension culture and
spontaneous contractile activity was assessed. On day 8, selected EBs were
dissociated to form monolayers for electrophysiological characterization using
calcium transient mapping. Nitric oxide treatment led to increased numbers of
stem cell-derived cardiomyocytes (SC-CMs) relative to non-treated EBs after 8
days in suspension culture. Increased incidence of spontaneous contraction and
frequency of contraction were observed from days 8-14 in EBs receiving nitric
oxide treatment in comparison to control. Expression of cardiac markers and
functional proteins was visualized using immunocytochemistry and gene expression
was assessed using qPCR. Cardiac-specific proteins were present in both CysNO
treated and control SC-CMs; however, CysNO treatment during differentiation
significantly increased betaMHC gene expression in SC-CMs relative to control SC
CMs. Furthermore, increased calcium transient velocity and decreased calcium
transient duration was observed for CysNO-treated SC-CMs in comparison to control
SC-CMs. Soluble nitric oxide donors, including S-nitrosocysteine, have advantages
over other bioactive molecules for use in scalable culture systems in driving
cardiac differentiation, since they are inexpensive and the diffusivity of nitric
oxide is relatively high. By enabling maintenance of spontaneous contraction in
suspension culture and progressing electrophysiological function of resulting SC
CMs toward a more mature phenotype, long-term application of S-nitrosocysteine
was shown to be beneficial during cardiac differentiation. Taken together, these
results demonstrate the efficiency of nitric oxide as a signaling compound, with
implications in the improvement of pluripotent stem cell-derived cardiomyocyte
maturation in large-scale culture systems.
PMID- 26444683
TI - Time Course of Cell Sheet Adhesion to Porcine Heart Tissue after Transplantation.
AB - Multilayered cell sheets have been produced from bone marrow-derived mesenchymal
stem cells (MSCs) for investigating their adhesion properties onto native porcine
heart tissue. Once MSCs reached confluence after a 7-day culture on a temperature
responsive culture dish, a MSCs monolayer spontaneously detached itself from the
dish, when the culture temperature was reduced from 37 to 20 degrees C. The basal
extracellular matrix (ECM) proteins of the single cell sheet are preserved,
because this technique requires no proteolytic enzymes for harvesting cell sheet,
which become a basic building block for assembling a multilayer cell sheet. The
thickness of multilayered cell sheets made from three MSC sheets was found to be
approximately 60 MUm. For investigating the adhesion properties of the basal and
apical sides, the multilayered cell sheets were transplanted onto the surface of
the heart's left ventricle. Multilayered cell sheets were histological
investigated at 15, 30, 45 and 60 minutes after transplantation by hematoxylin
eosin (HE) and azan dyes to determine required time for the adhesion of the
multilayered sheets following cell-sheet transplantation. The results showed that
only the basal side of multilayered cell sheets significantly enhanced the sheets
adhesion onto the surface of heart 30 minutes after transplantation. This study
concluded that (1) cell sheets had to be transplanted with its basal side onto
the surface of heart tissue and (2) at least 30 minutes were necessary for
obtaining the histological adhesion of the sheets to the heart tissue. This study
provided clinical evidence and parameters for the successful application of MSC
sheets to the myocardium and allowed cell sheet technology to be adapted clinical
cell-therapy for myocardial diseases.
PMID- 26444684
TI - SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer
collateral synapses and affects contextual fear memory.
AB - Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal
development and differentiation, such as axon specifications and maturation in
central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B
is associated with synaptic vesicles and the active zone cytomatrix; however, how
SAD-B regulates neurotransmission and synaptic plasticity in vivo remains
unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre
synaptic kinase in the brain. We found that the paired-pulse ratio was
significantly enhanced at Shaffer collateral synapses in the hippocampal CA1
region in SAD-B KO mice compared with wild-type littermates. We also found that
the frequency of the miniature excitatory post-synaptic current was decreased in
SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency
synaptic stimulation was significantly enhanced in SAD-B KO mice. These results
suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic
terminals and is involved in vesicular trafficking and/or regulation of the
readily releasable pool size. Finally, we found that hippocampus-dependent
contextual fear learning was significantly impaired in SAD-B KO mice. These
observations suggest that SAD-B kinase plays pivotal roles in controlling
vesicular release properties and regulating hippocampal function in the mature
brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in
neuronal development and differentiation, but their roles in mature brains were
only partially known. Here, we demonstrated, at mature pre-synaptic terminals,
that SAD-B regulates vesicular release probability and synaptic plasticity.
Moreover, hippocampus-dependent contextual fear learning was significantly
impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in
controlling vesicular release properties and regulating hippocampal function in
the mature brain.
PMID- 26444685
TI - Evaluation of cotton stalk hydrolysate for xylitol production.
AB - Cotton stalk is a widely distributed and abundant lignocellulosic waste found in
Turkey. Because of its rich xylose content, it can be a promising source for the
production of xylitol. Xylitol can be produced by chemical or biotechnological
methods. Because the biotechnological method is a simple process with great
substrate specificity and low energy requirements, it is more of an economic
alternative for the xylitol production. This study aimed to use cotton stalk for
the production of xylitol with Candida tropicalis Kuen 1022. For this purpose,
the combined effects of different oxygen concentration, inoculum level and
substrate concentration were investigated to obtain high xylitol yield and
volumetric xylitol production rate. Candida tropicalis Kuen 1022 afforded
different concentrations of xylitol depending on xylose concentration, inoculum
level, and oxygen concentration. The optimum xylose, yeast concentration, and
airflow rate for cotton stalk hydrolysate were found as 10.41 g L(-1), 0.99 g L(
1), and 1.02 vvm, respectively, and under these conditions, xylitol yield and
volumetric xylitol production rate were obtained as 36% and 0.06 g L(-1) hr(-1),
respectively. The results of this study show that cotton stalk can serve as a
potential renewable source for the production of xylitol.
PMID- 26444686
TI - Planar Heterojunction Perovskite Solar Cells Incorporating Metal-Organic
Framework Nanocrystals.
AB - Zr-based porphyrin metal-organic framework (MOF-525) nanocrystals with a crystal
size of about 140 nm are synthesized and incorporated into perovskite solar
cells. The morphology and crystallinity of the perovskite thin film are enhanced
since the micropores of MOF-525 allow the crystallization of perovskite to occur
inside; this observation results in a higher cell efficiency of the obtained
MOF/perovskite solar cell.
PMID- 26444687
TI - Thermal Modelling Analysis of Spiral Wound Supercapacitor under Constant-Current
Cycling.
AB - A three-dimensional modelling approach is used to study the effects of operating
and ambient conditions on the thermal behaviour of the spiral wound
supercapacitor. The transient temperature distribution during cycling is obtained
by using the finite element method with an implicit predictor-multicorrector
algorithm. At the constant current of 2A, the results show that the maximum
temperature appears in core area. After 5 cycles, the maximum temperature is 34.5
degrees C, while in steady state, it's up to 42.5 degrees C. This paper further
studies the relationship between the maximum temperature and charge-discharge
current. The maximum temperature will be more than 60 degrees C after 5 cycles at
the current of 4A, and cooling measurements should be taken at that time. It can
provide thoughts on inner temperature field distribution and structure design of
the spiral wound supercapacitor in working process.
PMID- 26444688
TI - Preparation and Characterization of Composites Based on Polylactic Acid and
Beeswax with Improved Water Vapor Barrier Properties.
AB - Beeswax and a plasticizer (ATBC) were added to polylactic acid (PLA) films in
order to enhance the water vapor barrier properties of the films. Beeswax
improved the barrier properties; the water vapor permeability in the composite
containing 1% beeswax was 58% lower than that of the neat PLA. Fourier transform
infrared spectroscopy and X-ray diffraction analysis revealed that the
incorporation of beeswax and ATBC had so little effect on the PLA structure. In
addition, the structure of PLA did not vary substantially with the additions. The
surfaces of the composites were examined by using field emission scanning
electron microscopy. Differential scanning calorimetry results showed that the
degree of crystallinity of the PLA films increased with the addition of beeswax
and ATBC. However, the tensile strength and elongation at break of the composites
containing beeswax were up to approximately 50% lower than those of the neat PLA.
Although further study is needed to improve the mechanical properties, the
aforementioned results showed that the PLA barrier properties can be improved by
the incorporation of a small amount of beeswax and ATBC. PRACTICAL APPLICATION:
The results of this study can be applied for the preparation of PLA composite
films with improved barrier properties. Such biodegradable films are extremely
useful for applications in the food packaging industry.
PMID- 26444689
TI - Abacus Training Affects Math and Task Switching Abilities and Modulates Their
Relationships in Chinese Children.
AB - Our previous work demonstrated that abacus-based mental calculation (AMC), a
traditional Chinese calculation method, could help children improve their math
abilities (e.g. basic arithmetical ability) and executive function (e.g. working
memory). This study further examined the effects of long-term AMC training on
math ability in visual-spatial domain and the task switching component of
executive function. More importantly, this study investigated whether AMC
training modulated the relationship between math abilities and task switching.
The participants were seventy 7-year-old children who were randomly assigned into
AMC and control groups at primary school entry. Children in AMC group received 2
hour AMC training every week since primary school entry. On the contrary,
children in the control group had never received any AMC training. Math and task
switching abilities were measured one year and three years respectively after AMC
training began. The results showed that AMC children performed better than their
peers on math abilities in arithmetical and visual-spatial domains. In addition,
AMC group responded faster than control group in the switching task, while no
group difference was found in switch cost. Most interestingly, group difference
was present in the relationships between math abilities and switch cost. These
results implied the effect of AMC training on math abilities as well as its
relationship with executive function.
PMID- 26444690
TI - Structure Identification of Uncertain Complex Networks Based on Anticipatory
Projective Synchronization.
AB - This paper investigates a method to identify uncertain system parameters and
unknown topological structure in general complex networks with or without time
delay. A complex network, which has uncertain topology and unknown parameters, is
designed as a drive network, and a known response complex network with an input
controller is designed to identify the drive network. Under the proposed input
controller, the drive network and the response network can achieve anticipatory
projective synchronization when the system is steady. Lyapunov theorem and
Barbalat's lemma guarantee the stability of synchronization manifold between two
networks. When the synchronization is achieved, the system parameters and
topology in response network can be changed to equal with the parameters and
topology in drive network. A numerical example is given to show the effectiveness
of the proposed method.
PMID- 26444691
TI - Correction: KORRIGAN1 Interacts Specifically with Integral Components of the
Cellulose Synthase Machinery.
PMID- 26444693
TI - Applications of Nanotechnology in the Management of Cancer: Miniature Technology,
Great Potential.
PMID- 26444692
TI - Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among
Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial.
AB - IMPORTANCE: Saline (0.9% sodium chloride) is the most commonly administered
intravenous fluid; however, its use may be associated with acute kidney injury
(AKI) and increased mortality. OBJECTIVE: To determine the effect of a buffered
crystalloid compared with saline on renal complications in patients admitted to
the intensive care unit (ICU). DESIGN AND SETTING: Double-blind, cluster
randomized, double-crossover trial conducted in 4 ICUs in New Zealand from April
2014 through October 2014. Three ICUs were general medical and surgical ICUs; 1
ICU had a predominance of cardiothoracic and vascular surgical patients.
PARTICIPANTS: All patients admitted to the ICU requiring crystalloid fluid
therapy were eligible for inclusion. Patients with established AKI requiring
renal replacement therapy (RRT) were excluded. All 2278 eligible patients were
enrolled; 1152 of 1162 patients (99.1%) receiving buffered crystalloid and 1110
of 1116 patients (99.5%) receiving saline were analyzed. INTERVENTIONS:
Participating ICUs were assigned a masked study fluid, either saline or a
buffered crystalloid, for alternating 7-week treatment blocks. Two ICUs commenced
using 1 fluid and the other 2 commenced using the alternative fluid. Two
crossovers occurred so that each ICU used each fluid twice over the 28 weeks of
the study. The treating clinician determined the rate and frequency of fluid
administration. MAIN OUTCOMES AND MEASURES: The primary outcome was proportion of
patients with AKI (defined as a rise in serum creatinine level of at least 2-fold
or a serum creatinine level of >=3.96 mg/dL with an increase of >=0.5 mg/dL);
main secondary outcomes were incidence of RRT use and in-hospital mortality.
RESULTS: In the buffered crystalloid group, 102 of 1067 patients (9.6%) developed
AKI within 90 days after enrollment compared with 94 of 1025 patients (9.2%) in
the saline group (absolute difference, 0.4% [95% CI, -2.1% to 2.9%]; relative
risk [RR], 1.04 [95% CI, 0.80 to 1.36]; P = .77). In the buffered crystalloid
group, RRT was used in 38 of 1152 patients (3.3%) compared with 38 of 1110
patients (3.4%) in the saline group (absolute difference, -0.1% [95% CI, -1.6% to
1.4%]; RR, 0.96 [95% CI, 0.62 to 1.50]; P = .91). Overall, 87 of 1152 patients
(7.6%) in the buffered crystalloid group and 95 of 1110 patients (8.6%) in the
saline group died in the hospital (absolute difference, -1.0% [95% CI, -3.3% to
1.2%]; RR, 0.88 [95% CI, 0.67 to 1.17]; P = .40). CONCLUSIONS AND RELEVANCE:
Among patients receiving crystalloid fluid therapy in the ICU, use of a buffered
crystalloid compared with saline did not reduce the risk of AKI. Further large
randomized clinical trials are needed to assess efficacy in higher-risk
populations and to measure clinical outcomes such as mortality. TRIAL
REGISTRATION: clinicaltrials.gov Identifier: ACTRN12613001370796.